PMID- 17428850
TI  - VP3, a structural protein of infectious pancreatic necrosis virus, interacts with
      RNA-dependent RNA polymerase VP1 and with double-stranded RNA.
AB  - Infectious pancreatic necrosis virus (IPNV) is a bisegmented, double-stranded RNA
      (dsRNA) virus of the Birnaviridae family that causes widespread disease in
      salmonids. Its two genomic segments are encapsulated together with the viral RNA
      dependent RNA polymerase, VP1, and the assumed internal protein, VP3, in a single
      shell capsid composed of VP2. Major aspects of the molecular biology of IPNV,
      such as particle assembly and interference with host macromolecules, are as yet
      poorly understood. To understand the infection process, analysis of viral protein
      interactions is of crucial importance. In this study, we focus on the interaction
      properties of VP3, the suggested key organizer of particle assembly in
      birnaviruses. By applying the yeast two-hybrid system in combination with
      coimmunoprecipitation, VP3 was proven to bind to VP1 and to self-associate
      strongly. In addition, VP3 was shown to specifically bind to dsRNA in a sequence
      independent manner by in vitro pull-down experiments. The binding between VP3 and
      VP1 was not dependent on the presence of dsRNA. Deletion analyses mapped the VP3
      self-interaction domain within the 101 N-terminal amino acids and the VP1
      interaction domain within the 62 C-terminal amino acids of VP3. The C-terminal
      end was also crucial but not sufficient for the dsRNA binding capacity of VP3.
      For VP1, the 90 C-terminal amino acids constituted the only dispensable part for
      maintaining VP3-binding ability. Kinetic analysis revealed the presence of VP1
      VP3 complexes prior to the formation of mature virions in IPNV-infected CHSE-214
      cells, which indicates a role in promoting the assembly process.

PMID- 17428851
TI  - Rotavirus infection of infant and young adult nonobese diabetic mice involves
      extraintestinal spread and delays diabetes onset.
AB  - Rotaviruses have been implicated as a possible viral trigger for exacerbations in
      islet autoimmunity, suggesting they might modulate type 1 diabetes development.
      In this study, the ability of rotavirus strain RRV to infect the pancreas and
      affect insulitis and diabetes was examined in nonobese diabetic (NOD) mice, an
      experimental model of type 1 diabetes. Mice were inoculated either orally or
      intraperitoneally as infants or young adults. In infant mice inoculated orally,
      rotavirus antigen was detected in pancreatic macrophages outside islets and
      infectious virus was found in blood cells, pancreas, spleen, and liver.
      Extraintestinal RRV spread and pancreatic presence of infectious virus also
      occurred in intraperitoneally inoculated infant and adult mice. The initiation of
      insulitis was unaltered by infection. The onset of diabetes was delayed in infant
      mice inoculated orally and infant and adult mice inoculated intraperitoneally. In
      contrast, adult mice inoculated orally showed no evidence of pancreatic RRV, the
      lowest rate of detectable RRV replication, and no diabetes modulation. Thus, the
      ability of RRV infection to modulate diabetes development in infant and young
      adult NOD mice was related to the overall extent of detectable virus replication
      and the presence of infectious virus extraintestinally, including in the
      pancreas. These studies show that RRV infection of infant and young adult NOD
      mice provides significant protection against diabetes. As these findings do not
      support the hypothesis that rotavirus triggers autoimmunity related to type 1
      diabetes, further research is needed to resolve this issue.

PMID- 17428852
TI  - Effect of preexisting immunity to adenovirus human serotype 5 antigens on the
      immune responses of nonhuman primates to vaccine regimens based on human- or
      chimpanzee-derived adenovirus vectors.
AB  - In this study we compared a prime-boost regimen with two serologically distinct
      replication-defective adenovirus (Ad) vectors derived from chimpanzee serotypes
      C68 and C1 expressing Gag, Pol, gp140, and Nef of human immunodeficiency virus
      type 1 with a regimen in which replication-defective Ad vectors of the human
      serotype 5 (AdHu5) were given twice. Experiments were conducted in rhesus
      macaques that had or had not been preexposed to antigens of AdHu5. There was no
      significant difference in T-cell responses tested from peripheral blood of the
      different groups, although responses were overall highest in nonpreexposed
      animals immunized with the chimpanzee Ad vectors. Preexisting immunity to AdHu5
      completely inhibited induction of transgene product-specific antibodies by the
      AdHu5 vectors without affecting antibody responses to the chimpanzee vectors.
      Upon euthanasia, T-cell responses were tested from a number of tissues.
      Preexisting immunity to AdHu5, commonly found in humans, changed the homing
      pattern of vaccine-induced T cells. In AdHu5-preexposed animals vaccinated with
      the chimpanzee Ad vectors, frequencies of transgene-specific T cells were higher
      in spleens than in blood, and in most preexposed animals vaccinated either with
      AdHu5 vectors or chimpanzee adenovirus vectors, frequencies of such T cells were
      exceptionally high in livers. The latter results indicate that analysis of T-cell
      responses solely from blood mononuclear cells of vaccine recipients may not
      suffice to compare the potencies of different vaccine regimens.

PMID- 17428853
TI  - Differential outcome of tolerance induction in naive versus activated Theiler's
      virus epitope-specific CD8+ cytotoxic T cells.
AB  - Tolerance induced by the intravenous injection of peptide-pulsed, ethylene
      carbodiimide (ECDI)-fixed splenic antigen-presenting cells (Ag-SP) is a safe and
      effective method of inducing specific unresponsiveness in CD4+ T cells for the
      prevention and treatment of a variety of autoimmune diseases. We determined
      whether Ag-SP tolerance could also be used to tolerize CD8+ T cells. We show in
      the Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease
      model of multiple sclerosis that CD8+ T cells specific for both dominant and
      subdominant epitopes can be rendered tolerant. Interestingly, although virus
      clearance was delayed, lack of the virus-specific cytotoxic T-lymphocyte response
      did not result in the conversion of normally TMEV-resistant C57BL/6 mice to a
      susceptible phenotype. Importantly, we found that Ag-SP tolerance may not be a
      practical treatment for human diseases in which CD8+ T cells play a major role in
      pathogenesis, as tolerance induction in mice previously infected with TMEV led to
      a severe, often fatal reaction.

PMID- 17428854
TI  - Genomic and morphological features of a banchine polydnavirus: comparison with
      bracoviruses and ichnoviruses.
AB  - Many ichneumonid and braconid endoparasitoids inject a polydnavirus (PDV) into
      their caterpillar hosts during oviposition. The viral entities carried by wasps
      of these families are referred to as "ichnoviruses" (IVs) and "bracoviruses"
      (BVs), respectively. All IV genomes characterized to date are found in wasps of
      the subfamily Campopleginae; consequently, little is known about PDVs found in
      wasps of the subfamily Banchinae, the only other ichneumonid taxon thus far shown
      to carry these viruses. Here we report on the genome sequence and virion
      morphology of a PDV carried by the banchine parasitoid Glypta fumiferanae. With
      an aggregate genome size of approximately 290 kb and 105 genome segments, this
      virus displays a degree of genome segmentation far greater than that reported for
      BVs or IVs. The size range of its genome segments is also lower than those in the
      latter two groups. As reported for other PDVs, the predicted open reading frames
      of this virus cluster into gene families, including the protein tyrosine
      phosphatase (PTP) and viral ankyrin (ank) families, but phylogenetic analysis
      indicates that ank genes of the G. fumiferanae virus are not embedded within the
      IV lineage, while its PTPs and those of BVs form distinct clusters. The banchine
      PDV genome also encodes a novel family of NTPase-like proteins displaying a pox
      D5 domain. The unique genomic features of the first banchine virus examined,
      along with the morphological singularities of its virions (IV-like nucleocapsids,
      but enveloped in groups like some of the BVs), suggest that they could have an
      origin distinct from those of IVs and BVs.

PMID- 17428855
TI  - The X protein of borna disease virus serves essential functions in the viral
      multiplication cycle.
AB  - The X gene of Borna disease virus (BDV) encodes a nonstructural 10-kDa protein
      that can interact with viral polymerase cofactor P, thus regulating polymerase
      activity. It remained unknown whether X is essential for virus multiplication.
      All our attempts to generate mutant BDV with a nonfunctional X gene proved
      unsuccessful. However, a mutant virus with an inactive X gene was able to
      replicate in Vero cells if an artificial gene cassette encoding X was inserted at
      a site near the 5' end of the viral genome. These results indicate that X
      performs essential viral functions.

PMID- 17428856
TI  - New structure model for the packaging signal in the genome of group IIa
      coronaviruses.
AB  - A 190-nucleotide (nt) packaging signal (PS) located in the 3' end of open reading
      frame 1b in the mouse hepatitis virus, a group IIa coronavirus, was previously
      postulated to direct genome RNA packaging. Based on phylogenetic data and
      structure probing, we have identified a 95-nt hairpin within the 190-nt PS domain
      which is conserved in all group IIa coronaviruses but not in the severe acute
      respiratory syndrome coronavirus (group IIb), group I coronaviruses, or group III
      coronaviruses. The hairpin is composed of six copies of a repeating structural
      subunit that consists of 2-nt bulges and 5-bp stems. We propose that repeating AA
      bulges are characteristic features of group IIa PSs.

PMID- 17428857
TI  - Human immunodeficiency virus type 1 variants resistant to first- and second
      version fusion inhibitors and cytopathic in ex vivo human lymphoid tissue.
AB  - Human immunodeficiency virus type 1 (HIV-1) fusion inhibitors blocking viral
      entry by binding the gp41 heptad repeat 1 (HR1) region offer great promise for
      antiretroviral therapy, and the first of these inhibitors, T20 (Fuzeon;
      enfuvirtide), is successfully used in the clinic. It has been reported previously
      that changes in the 3-amino-acid GIV motif at positions 36 to 38 of gp41 HR1
      mediate resistance to T20 but usually not to second-version fusion inhibitors,
      such as T1249, which target an overlapping but distinct region in HR1 including a
      conserved hydrophobic pocket (HP). Based on the common lack of cross-resistance
      and the difficulty of selecting T1249-resistant HIV-1 variants, it has been
      suggested that the determinants of resistance to first- and second-version fusion
      inhibitors may be different. To further assess HIV-1 resistance to fusion
      inhibitors and to analyze where changes in HR1 are tolerated, we randomized 16
      codons in the HR1 region, including those making contact with HR2 codons and/or
      encoding residues in the GIV motif and the HP. We found that changes only at
      positions 37I, 38V, and 40Q near the N terminus of HR1 were tolerated. The
      propagation of randomly gp41-mutated HIV-1 variants in the presence of T1249
      allowed the effective selection of highly resistant forms, all containing changes
      in the IV residues. Overall, the extent of T1249 resistance was inversely
      correlated to viral fitness and cytopathicity. Notably, one HIV-1 mutant showing
      approximately 10-fold-reduced susceptibility to T1249 inhibition replicated with
      wild type-like kinetics and caused substantial CD4+-T-cell depletion in ex vivo
      infected human lymphoid tissue in the presence and absence of an inhibitor. Taken
      together, our results show that the GIV motif also plays a key role in resistance
      to second-version fusion inhibitors and suggest that some resistant HIV-1
      variants may be pathogenic in vivo.

PMID- 17428858
TI  - Herpes simplex virus type 1 induces CD83 degradation in mature dendritic cells
      with immediate-early kinetics via the cellular proteasome.
AB  - Mature dendritic cells (DCs) are the most potent antigen-presenting cells within
      the human immune system. However, Herpes simplex virus type 1 (HSV-1) is able to
      interfere with DC biology and to establish latency in infected individuals. In
      this study, we provide new insights into the mechanism by which HSV-1 disarms DCs
      by the manipulation of CD83, a functionally important molecule for DC activation.
      Fluorescence-activated cell sorter (FACS) analyses revealed a rapid
      downmodulation of CD83 surface expression within 6 to 8 h after HSV-1 infection,
      in a manner strictly dependent on viral gene expression. Soluble CD83 enzyme
      linked immunosorbent assays, together with Western blot analysis, demonstrated
      that CD83 rapidly disappears from the cell surface after contact with HSV-1 by a
      mechanism that involves protein degradation rather than shedding of CD83 from the
      cell surface into the medium. Infection experiments with an ICP0 deletion mutant
      demonstrated an important role for this viral immediate-early protein during CD83
      degradation, since this particular mutant strain leads to strongly reduced CD83
      degradation. This hypothesis was further strengthened by cotransfection of
      plasmids expressing CD83 and ICP0 into 293T cells, which led to significantly
      reduced accumulation of CD83. In strong contrast, transfection of plasmids
      expressing CD83 and a mutant ICP0 defective in its RING finger-mediated E3
      ubiquitin ligase function did not reduce CD83 expression. Inhibition of the
      proteasome, the cellular protein degradation machinery, almost completely
      restored CD83 surface expression during HSV-1 infection, indicating that
      proteasome-mediated degradation and HSV-1 ICP0 play crucial roles in this novel
      viral immune escape mechanism.

PMID- 17428859
TI  - US3 of herpes simplex virus type 1 encodes a promiscuous protein kinase that
      phosphorylates and alters localization of lamin A/C in infected cells.
AB  - The herpes simplex virus type 1 (HSV-1) US3 gene encodes a serine/threonine
      kinase that, when inactivated, causes capsids to aggregate aberrantly between the
      inner and outer nuclear membranes (INM and ONM, respectively) within
      evaginations/extensions of the perinuclear space. In both Hep2 cells and an
      engineered cell line derived from Hep2 cells expressing lamin A/C fused to
      enhanced green fluorescent protein (eGFP-lamin A/C), lamin A/C localized mostly
      in a reticular pattern with small regions of the INM devoid of eGFP-lamin A/C
      when they were either mock infected or infected with wild-type HSV-1(F). Cells
      infected with HSV-1(F) also contained some larger diffuse regions lacking lamin
      A/C. Proteins UL31 and UL34, markers of potential envelopment sites at the INM
      and perinuclear virions, localized within the regions devoid of lamin A/C and
      also in regions containing lamin A/C. Similar to previous observations with Vero
      cells (S. L. Bjerke and R. J. Roller, Virology 347:261-276, 2006), the proteins
      UL34 and UL31 localized exclusively in very discrete regions of the nuclear
      lamina lacking lamin A/C in the absence of US3 kinase activity. To determine how
      US3 alters lamin A/C distribution, US3 was purified and shown to phosphorylate
      lamin A/C at multiple sites in vitro, despite the presence of only one putative
      US3 kinase consensus site in the lamin A/C sequence. US3 kinase activity was also
      sufficient to invoke partial solubilization of lamin A/C from permeabilized Hep2
      cell nuclei in an ATP-dependent manner. Two-dimensional electrophoretic analyses
      of lamin A/C revealed that lamin A/C is phosphorylated in HSV-infected cells, and
      the full spectrum of phosphorylation requires US3 kinase activity. These data
      suggest that US3 kinase activity regulates HSV-1 capsid nuclear egress at least
      in part by phosphorylation of lamin A/C.

PMID- 17428860
TI  - Mutagenesis of the herpesvirus saimiri terminal repeat region reveals important
      elements for virus production.
AB  - Deletion of the terminal repeats (TR) from herpesvirus saimiri (HVS) renders it
      unable to produce infectious virus or generate plaques. However, a TR-deleted HVS
      bacterial artificial chromosome can form replication compartments.
      Complementation of this mutant shows that one copy of the TR, plus the right
      junction of the genome with the TR, is sufficient for efficient plaque formation
      and generation of infectious virus. Within the TR unit, the region around the
      cleavage site of the genome appears both necessary and sufficient for virus
      production. Analysis of episomes from productive cells indicates a propensity to
      amplify TR numbers during the lytic cycle.

PMID- 17428861
TI  - Potent rescue of human immunodeficiency virus type 1 late domain mutants by
      ALIX/AIP1 depends on its CHMP4 binding site.
AB  - The release of human immunodeficiency virus type 1 (HIV-1) and of other
      retroviruses from certain cells requires the presence of distinct regions in Gag
      that have been termed late assembly (L) domains. HIV-1 harbors a PTAP-type L
      domain in the p6 region of Gag that engages an endosomal budding machinery
      through Tsg101. In addition, an auxiliary L domain near the C terminus of p6
      binds to ALIX/AIP1, which functions in the same endosomal sorting pathway as
      Tsg101. In the present study, we show that the profound release defect of HIV-1 L
      domain mutants can be completely rescued by increasing the cellular expression
      levels of ALIX and that this rescue depends on an intact ALIX binding site in p6.
      Furthermore, the ability of ALIX to rescue viral budding in this system depended
      on two putative surface-exposed hydrophobic patches on its N-terminal Bro1
      domain. One of these patches mediates the interaction between ALIX and the ESCRT
      III component CHMP4B, and mutations which disrupt the interaction also abolish
      the activity of ALIX in viral budding. The ability of ALIX to rescue a PTAP
      mutant also depends on its C-terminal proline-rich domain (PRD), but not on the
      binding sites for Tsg101, endophilin, CIN85, or for the newly identified binding
      partner, CMS, within the PRD. Our data establish that ALIX can have a dramatic
      effect on HIV-1 release and suggest that the ability to use ALIX may allow HIV-1
      to replicate in cells that express only low levels of Tsg101.

PMID- 17428862
TI  - Induction of apoptosis by the severe acute respiratory syndrome coronavirus 7a
      protein is dependent on its interaction with the Bcl-XL protein.
AB  - The severe acute respiratory syndrome coronavirus (SARS-CoV) 7a protein, which is
      not expressed by other known coronaviruses, can induce apoptosis in various cell
      lines. In this study, we show that the overexpression of Bcl-XL, a prosurvival
      member of the Bcl-2 family, blocks 7a-induced apoptosis, suggesting that the
      mechanism for apoptosis induction by 7a is at the level of or upstream from the
      Bcl-2 family. Coimmunoprecipitation experiments showed that 7a interacts with Bcl
      XL and other prosurvival proteins (Bcl-2, Bcl-w, Mcl-1, and A1) but not with the
      proapoptotic proteins (Bax, Bak, Bad, and Bid). A good correlation between the
      abilities of 7a deletion mutants to induce apoptosis and to interact with Bcl-XL
      was observed, suggesting that 7a triggers apoptosis by interfering directly with
      the prosurvival function of Bcl-XL. Interestingly, amino acids 224 and 225 within
      the C-terminal transmembrane domain of Bcl-XL are essential for the interaction
      with the 7a protein, although the BH3 domain of Bcl-XL also contributes to this
      interaction. In addition, fractionation experiments showed that 7a colocalized
      with Bcl-XL at the endoplasmic reticulum as well as the mitochondria, suggesting
      that they may form complexes in different membranous compartments.

PMID- 17428863
TI  - Mucosal innate immune response associated with a timely humoral immune response
      and slower disease progression after oral transmission of simian immunodeficiency
      virus to rhesus macaques.
AB  - Mucosal transmission is the predominant mode of human immunodeficiency virus
      (HIV) infection worldwide, and the mucosal innate interferon response represents
      an important component of the earliest host response to the infection. Our goal
      here was to assess the changes in mRNA expression of innate mucosal genes after
      oral simian immunodeficiency virus (SIV) inoculation of rhesus macaques (Macaca
      mulatta) that were followed throughout their course of disease progression. The
      SIV plasma viral load was highest in the macaque that progressed rapidly to
      simian AIDS (99 days) and lowest in the macaque that progressed more slowly (>700
      days). The mRNA levels of six innate/effector genes in the oral mucosa indicated
      that slower disease progression was associated with increased expression of these
      genes. This distinction was most evident when comparing the slowest-progressing
      macaque to the intermediate and rapid progressors. Expression levels of alpha and
      gamma interferons, the antiviral interferon-stimulated gene product 2'-5'
      oligoadenylate synthetase (OAS), and the chemokines CXCL9 and CXCL10 in the slow
      progressor were elevated at each of the three oral mucosal biopsy time points
      examined (day 2 to 4, 14 to 21, and day 70 postinfection). In contrast, the more
      rapidly progressing macaques demonstrated elevated levels of these
      cytokine/chemokine mRNA at lymph nodes, coincident with decreased levels at the
      mucosal sites, and a decreased ability to elicit an effective anti-SIV antibody
      response. These data provide evidence that a robust mucosal innate/effector
      immune response is beneficial following lentiviral exposure; however, it is
      likely that the anatomical location and timing of the response need to be
      coordinated to permit an effective immune response able to delay progression to
      simian AIDS.

PMID- 17428864
TI  - Comparative study of methods for detecting sequence compartmentalization in human
      immunodeficiency virus type 1.
AB  - Human immunodeficiency virus (HIV) infects different organs and tissues. During
      these infection events, subpopulations of HIV type 1 (HIV-1) develop and, if
      viral trafficking is restricted between subpopulations, the viruses can follow
      independent evolutionary histories, i.e., become compartmentalized. This
      phenomenon is usually detected via comparative sequence analysis and has been
      reported for viruses isolated from the central nervous system (CNS) and the
      genital tract. Several approaches have been proposed to study the
      compartmentalization of HIV sequences, but to date, no rigorous comparison of the
      most commonly employed methods has been made. In this study, we systematically
      compared inferences made by six different methods for detecting
      compartmentalization based on three data sets: (i) a sample of 45 patients with
      sequences gathered from the CNS, (ii) sequences from the female genital tract of
      18 patients, and (iii) a set of simulated sequences. We found that different
      methods often reached contradictory conclusions. Methods based on the topology of
      a phylogenetic tree derived from clonal sequences were generally more sensitive
      in detecting compartmentalization than those that relied solely upon pairwise
      genetic distances between sequences. However, as the branching structure in a
      phylogenetic tree is often uncertain, especially for short, low-diversity, or
      recombinant sequences, tree-based approaches may need to be modified to take
      phylogenetic uncertainty into account. Given the frequently discordant
      predictions of different methods and the strengths and weaknesses of each
      particular methodology, we recommend that a suite of several approaches be used
      for reliable inference of compartmentalized population structure.

PMID- 17428865
TI  - Characterization and experimental transmission of an oncogenic papillomavirus in
      female macaques.
AB  - Cervical cancer is one of the leading causes of cancer mortality in women
      worldwide, yet few suitable animal models currently exist for study of this
      disease. Virtually all cases of cervical cancer in women are caused by specific
      types of genital human papillomavirus (HPV). In this study, we investigated
      naturally occurring genital PVs in female cynomolgus macaques (Macaca
      fascicularis) without breeding contact for at least 3.5 years. Exfoliated
      cervicovaginal cells from 19 of 54 animals tested positive for at least one PV.
      Seven different PVs were identified, including four novel genotypes and two
      genotypes (RhPV-d and RhPV-a) previously identified in rhesus macaques (Macaca
      mulatta). Four PV types were associated with cervical intraepithelial neoplasia
      (CIN), which resembled human CIN by endoscopy, cervical cytology, histology, and
      immunohistochemistry. The presence of CIN was highly associated with PV infection
      (P<0.0001). The most prevalent virus type was RhPV-d, which was identified in 60%
      of animals with CIN. An RhPV-d genome sequenced from a high-grade CIN lesion was
      found to be phylogenetically related to the highly oncogenic HPV16. Transfer of
      cervical cytobrush samples from donor animals naturally carrying RhPV-d resulted
      in new infections in 4 of 12 previously virus-free animals and abnormal cytology
      and histology in 1 of 4 infected animals after 18 weeks of infection.
      Experimental transmission was confirmed by E1/?E4 reverse transcription-PCR
      products and RhPV-d sequence identity with the donor variant. These findings
      identify key similarities between macaque and human oncogenic PVs which should
      prove useful in the study of viral persistence, carcinogenesis, and therapeutic
      development.

PMID- 17428866
TI  - Hepatitis B virus X protein stimulates the mitochondrial translocation of Raf-1
      via oxidative stress.
AB  - The human hepatitis B virus (HBV) X protein (HBx) plays a crucial role(s) in the
      viral life cycle and contributes to the onset of hepatocellular carcinoma (HCC).
      HBx caused the mitochondrial translocation of Raf-1 kinase either alone or in the
      context of whole-viral-genome transfections. Mitochondrial translocation of Raf-1
      is mediated by HBx-induced oxidative stress and was dependent upon the
      phosphorylation of Raf-1 at the serine338/339 and Y340/341 residues by p21
      activated protein kinase 1 and Src kinase, respectively. These studies provide an
      insight into the mechanisms by which HBV induces intracellular events relevant to
      liver disease pathogenesis, including HCC.

PMID- 17428867
TI  - Binding dynamics of hepatitis C virus' NS5A amphipathic peptide to cell and model
      membranes.
AB  - Membrane association of the hepatitis C virus NS5A protein is required for viral
      replication. This association is dependent on an N-terminal amphipathic helix
      (AH) within NS5A and is restricted to a subset of host cell intracellular
      membranes. The mechanism underlying this specificity is not known, but it may
      suggest a novel strategy for developing specific antiviral therapy. Here we have
      probed the mechanistic details of NS5A AH-mediated binding to both cell-derived
      and model membranes by use of biochemical membrane flotation and quartz crystal
      microbalance (QCM) with dissipation. With both assays, we observed AH-mediated
      binding to model lipid bilayers. When cell-derived membranes were coated on the
      quartz nanosensor, however, significantly more binding was detected, and the QCM
      derived kinetic measurements suggested the existence of an interacting receptor
      in the target membranes. Biochemical flotation assays performed with trypsin
      treated cell-derived membranes exhibited reduced AH-mediated membrane binding,
      while membrane binding of control cytochrome b5 remained unaffected. Similarly,
      trypsin treatment of the nanosensor coated with cellular membranes abolished AH
      peptide binding to the cellular membranes but did not affect the binding of a
      control lipid-binding peptide. These results therefore suggest that a protein
      plays a critical role in mediating and stabilizing the binding of NS5A's AH to
      its target membrane. These results also demonstrate the successful development of
      a new nanosensor technology ideal both for studying the interaction between a
      protein and its target membrane and for developing inhibitors of that
      interaction.

PMID- 17428868
TI  - Successful topical respiratory tract immunization of primates against Ebola
      virus.
AB  - Ebola virus causes outbreaks of severe viral hemorrhagic fever with high
      mortality in humans. The virus is highly contagious and can be transmitted by
      contact and by the aerosol route. These features make Ebola virus a potential
      weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces
      both systemic and local immune responses in the respiratory tract would be highly
      beneficial. We evaluated a common pediatric respiratory pathogen, human
      parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus.
      HPIV3 recombinants expressing the Ebola virus (Zaire species) surface
      glycoprotein (GP) alone or in combination with the nucleocapsid protein NP or
      with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were
      administered by the respiratory route to rhesus monkeys--in which HPIV3 infection
      is mild and asymptomatic--and were evaluated for immunogenicity and protective
      efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A
      single immunization with any construct expressing GP was moderately immunogenic
      against Ebola virus and protected 88% of the animals against severe hemorrhagic
      fever and death caused by Ebola virus. Two doses were highly immunogenic, and all
      of the animals survived challenge and were free of signs of disease and of
      detectable Ebola virus challenge virus. These data illustrate the feasibility of
      immunization via the respiratory tract against the hemorrhagic fever caused by
      Ebola virus. To our knowledge, this is the first study in which topical
      immunization through respiratory tract achieved prevention of a viral hemorrhagic
      fever infection in a primate model.

PMID- 17428869
TI  - Construction and characterization of a full-length infectious simian T-cell
      lymphotropic virus type 3 molecular clone.
AB  - Together with their simian T-cell lymphotropic virus (STLV) equivalent, human T
      cell lymphotropic virus type 1 (HTLV-1), HTLV-2, and HTLV-3 form the primate T
      cell lymphotropic virus (PTLV) group. Over the years, understanding the biology
      and pathogenesis of HTLV-1 and HTLV-2 has been widely improved by the creation of
      molecular clones. In contrast, so far, PTLV-3 experimental studies have been
      restricted to the overexpression of the tax gene using reporter assays. We have
      therefore decided to construct an STLV-3 molecular clone. We generated a full
      length STLV-3 proviral clone (8,891 bp) by PCR amplification of overlapping
      fragments. This STLV-3 molecular clone was then transfected into 293T cells.
      Reverse transcriptase PCR experiments followed by sequence analysis of the
      amplified products allowed us to establish that both gag and tax/rex mRNAs were
      transcribed. Western blotting further demonstrated the presence of the STLV-3
      p24gag protein in the cell culture supernatant from transfected cells. Transient
      transfection of 293T cells and of 293T-long terminal repeat-green fluorescent
      protein cells with the STLV-3 clone promoted syncytium formation, a hallmark of
      PTLV Env expression, as well as the appearance of fluorescent cells, also
      demonstrating that the Tax3 protein was expressed. Virus particles were visible
      by electron microscopy. These particles are infectious, as demonstrated by our
      cell-free-infection experiments with purified virions. All together, our data
      demonstrate that the STLV-3 molecular clone is functional and infectious. This
      clone will give us a unique opportunity to study in vitro the different pX
      transcripts and the putative presence of antisense transcripts and to evaluate
      the PTLV-3 pathogenicity in vivo.

PMID- 17428870
TI  - Analysis of murine hepatitis virus strain A59 temperature-sensitive mutant TS-LA6
      suggests that nsp10 plays a critical role in polyprotein processing.
AB  - Coronaviruses are the largest RNA viruses, and their genomes encode replication
      machinery capable of efficient replication of both positive- and negative-strand
      viral RNAs as well as enzymes capable of processing large viral polyproteins into
      putative replication intermediates and mature proteins. A model described
      recently by Sawicki et al. (S. G. Sawicki, D. L. Sawicki, D. Younker, Y. Meyer,
      V. Thiel, H. Stokes, and S. G. Siddell, PLoS Pathog. 1:e39, 2005), based upon
      complementation studies of known temperature-sensitive (TS) mutants of murine
      hepatitis virus (MHV) strain A59, proposes that an intermediate comprised of nsp4
      to nsp10/11 ( approximately 150 kDa) is involved in negative-strand synthesis.
      Furthermore, the mature forms of nsp4 to nsp10 are thought to serve as cofactors
      with other replicase proteins to assemble a larger replication complex
      specifically formed to transcribe positive-strand RNAs. In this study, we
      introduced a single-amino-acid change (nsp10:Q65E) associated with the TS-LA6
      phenotype into nsp10 of the infectious clone of MHV. Growth kinetic studies
      demonstrated that this mutation was sufficient to generate the TS phenotype at
      permissive and nonpermissive temperatures. Our results demonstrate that the TS
      mutant variant of nsp10 inhibits the main protease, 3CLpro, blocking its function
      completely at the nonpermissive temperature. These results implicate nsp10 as
      being a critical factor in the activation of 3CLpro function. We discuss how
      these findings challenge the current hypothesis that nsp4 to nsp10/11 functions
      as a single cistron in negative-strand RNA synthesis and analyze recent
      complementation data in light of these new findings.

PMID- 17428871
TI  - Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G
      exhibit defects in plus-strand DNA transfer and integration.
AB  - Encapsidation of host restriction factor APOBEC3G (A3G) into vif-deficient human
      immunodeficiency virus type 1 (HIV-1) blocks virus replication at least partly by
      C-to-U deamination of viral minus-strand DNA, resulting in G-to-A hypermutation.
      A3G may also inhibit HIV-1 replication by reducing viral DNA synthesis and
      inducing viral DNA degradation. To gain further insight into the mechanisms of
      viral inhibition, we examined the metabolism of A3G-exposed viral DNA. We
      observed that an overall 35-fold decrease in viral infectivity was accompanied by
      a five- to sevenfold reduction in viral DNA synthesis. Wild-type A3G induced an
      additional fivefold decrease in the amount of viral DNA that was integrated into
      the host cell genome and similarly reduced the efficiency with which HIV-1
      preintegration complexes (PICs) integrated into a target DNA in vitro. The A3G C
      terminal catalytic domain was required for both of these antiviral activities.
      Southern blotting analysis of PICs showed that A3G reduced the efficiency and
      specificity of primer tRNA processing and removal, resulting in viral DNA ends
      that are inefficient substrates for integration and plus-strand DNA transfer.
      However, the decrease in plus-strand DNA transfer did not account for all of the
      observed decrease in viral DNA synthesis associated with A3G. These novel
      observations suggest that HIV-1 cDNA produced in the presence of A3G exhibits
      defects in primer tRNA processing, plus-strand DNA transfer, and integration.

PMID- 17428872
TI  - The abundant R2 mRNA generated by aleutian mink disease parvovirus is
      tricistronic, encoding NS2, VP1, and VP2.
AB  - The abundant R2 mRNA encoded by the single left-end promoter of Aleutian mink
      disease parvovirus is tricistronic; it not only expresses the capsid proteins VP1
      and VP2 but is also the major source for the nonstructural protein NS2. A cis
      acting sequence within the NS2 gene was shown to be required for efficient capsid
      protein production, and its effect displayed a distinct location dependence.
      Ribosome transit through the upstream NS2 gene region was necessary for efficient
      VP1 and VP2 expression; however, neither ablation nor improvement of the NS2
      initiating AUG had an effect on capsid protein production, suggesting that the
      translation of the NS2 protein per se had little influence on VP1 and VP2
      expression. Thus, proper control of the alternative translation of the
      tricistronic R2 mRNA, a process critical for viral replication, is governed in a
      complex manner.

PMID- 17428873
TI  - Diminished potential for B-lymphoid differentiation after murine leukemia virus
      infection in vivo and in EML hematopoietic progenitor cells.
AB  - Infection with a recombinant murine-feline gammaretrovirus, MoFe2, or with the
      parent virus, Moloney murine leukemia virus, caused significant reduction in B
      lymphoid differentiation of bone marrow at 2 to 8 weeks postinfection. The
      suppression was selective, in that myeloid potential was significantly increased
      by infection. Analysis of cell surface markers and immunoglobulin H gene
      rearrangements in an in vitro model demonstrated normal B-lymphoid
      differentiation after infection but significantly reduced viability of
      differentiating cells. This reduction in viability may confer a selective
      advantage on undifferentiated lymphoid progenitors in the bone marrow of
      gammaretrovirus-infected animals and thereby contribute to the establishment of a
      premalignant state.

PMID- 17428874
TI  - Mutations in human immunodeficiency virus type 1 RNase H primer grip enhance 3'
      azido-3'-deoxythymidine resistance.
AB  - We recently observed that mutations in the human immunodeficiency type 1 (HIV-1)
      reverse transcriptase (RT) connection domain significantly increase 3'-azido-3'
      deoxythymidine (AZT) resistance up to 536 times over wild-type (WT) RT in the
      presence of thymidine analog resistance mutations (TAMs). These mutations also
      decreased RT template switching, suggesting that they altered the balance between
      nucleotide excision and template RNA degradation, which in turn increased AZT
      resistance. Several residues in the HIV-1 connection domain contact the primer
      strand and form an RNase H primer grip structure that helps to position the
      primer-template at the RNase H and polymerase active sites. To test the
      hypothesis that connection domain mutations enhanced AZT resistance by
      influencing the RNase H primer grip, we determined the effects of alanine
      substitutions in RNase H primer grip residues on nucleoside RT inhibitor
      resistance in the context of a WT, TAM-containing, or K65R-containing polymerase
      domain. Ten of the 11 RNase H primer grip mutations increased AZT resistance 20
      to 243 times above WT levels in the context of a TAM-containing polymerase
      domain. Furthermore, all mutations in the RNase H primer grip decreased template
      switching, suggesting that they reduced RNase H activity. These results
      demonstrate that mutations in the RNase H primer grip region can significantly
      enhance AZT resistance and support the hypothesis that mutations in the
      connection and RNase H domains can increase resistance by altering the RNase H
      primer grip region, changing interactions between RT and the template-primer
      complex and/or shifting the balance between the polymerase and RNase H
      activities.

PMID- 17428876
TI  - A Borna disease virus vector for expression of foreign genes in neurons of
      rodents.
AB  - An expression cassette for green fluorescent protein was successfully inserted at
      a site near the 5' end of the genome of Borna disease virus (BDV). When
      introduced into a mutant virus with highly active polymerase, the foreign gene
      was strongly expressed in neurons of infected rats. Since BDV can establish long
      term persistence in the central nervous system of rodents, it may be used to
      engineer efficient vectors for specific delivery of foreign genes into highly
      differentiated neurons.

PMID- 17428877
TI  - Views of BRCA gene mutation carriers on preimplantation genetic diagnosis as a
      reproductive option for hereditary breast and ovarian cancer.
AB  - BACKGROUND: In May 2006, the UK Human Fertilization and Embryology Authority
      (HFEA) approved use of preimplantation genetic diagnosis (PGD) for lower
      penetrance, late onset cancer susceptibility syndromes such as hereditary breast
      and ovarian cancer (HBOC). This is the first report on views of BRCA gene
      mutation carriers on use of PGD for HBOC. METHODS: Between December 2005 and
      February 2006, a postal survey of BRCA mutation carriers attending a Familial
      Cancer Clinic was undertaken. RESULTS: Of 102 women sent questionnaires, 52 (51%)
      responded. Thirty-nine (75%) felt it was acceptable to offer PGD for HBOC.
      Fifteen (37.5%) of 40 who had completed their families would personally have
      considered PGD if it had been available. Only one of seven (14%) contemplating a
      future pregnancy would consider PGD. Eighteen (35%) wrote extensively about their
      concerns including increasing availability of effective treatment and good
      quality of life. CONCLUSIONS: The majority of BRCA gene mutation carriers are
      supportive of offering PGD to others, thus endorsing the HFEA decision. However,
      most women would not consider it personally. Concerns raised highlight the need
      for regular HFEA reviews of the licensing criteria, as HBOC may cease to be a
      "serious life threatening illness" in the future.

PMID- 17428875
TI  - Epstein-Barr virus thymidine kinase is a centrosomal resident precisely localized
      to the periphery of centrioles.
AB  - The thymidine kinase (TK) encoded by Epstein-Barr virus (EBV) differs not only
      from that of the alphaherpesviruses but also from that of the gamma-2 herpesvirus
      subfamily. Because cellular location is frequently a determinant of regulatory
      function, to gain insight into additional role(s) of EBV TK and to uncover how
      the lymphocryptovirus and rhadinovirus enzymes differ, the subcellular
      localizations of EBV TK and the related cercopithecine herpesvirus-15 TK were
      investigated. We show that in contrast to those of the other family members, the
      gamma-1 herpesvirus TKs localize to the centrosome and even more precisely to the
      periphery of the centriole, tightly encircling the tubulin-rich centrioles in a
      microtubule-independent fashion. Centrosomal localization is observed in diverse
      cell types and occurs whether the protein is expressed independently or in the
      context of lytic EBV infection. Surprisingly, analysis of mutants revealed that
      the unique N-terminal domain was not critical for targeting to the centrosome,
      but rather, peptide sequences located C terminal to this domain were key. This is
      the first herpesvirus protein documented to reside in the centrosome, or
      microtubule-organizing center, an amembranous organelle that regulates the
      structural biology of the cell cycle through control of chromosome separation and
      cytokinesis. More recently, proteasome-mediated degradation of cell cycle
      regulatory proteins, production and loading of antigenic peptides onto HLA
      molecules, and transient homing of diverse virion proteins required for entry
      and/or egress have been shown to be coordinated at the centrosome. Potential
      implications of centrosomal localization for EBV TK function are discussed.

PMID- 17428878
TI  - Meiotic abnormalities in patients bearing complete AZFc deletion of Y chromosome.
AB  - BACKGROUND: We studied meiosis in three infertile patients presenting complete
      AZFc microdeletion and three controls. METHODS: Primary spermatocytes were
      immunolabeled with SCP3, BRCA1 and gammaH2AX. We quantified the leptotene,
      zygotene and pachytene stages, and pachytene abnormalities: asynapsis and
      fragmented and dotted synaptonemal complexes (SCs). RESULTS: SCP3 level was
      significantly higher in leptotene and zygotene (bouquet) stages in patients,
      suggesting AZFc may have a direct effect on early prophase. SCs were abnormal in
      77.3% of pachytene nuclei of patients versus 30.8% of controls. The two groups
      differed significantly (P < 0.001) in asynapsed nuclei, fragmented SC and dotted
      SCs. In patients, asynapsis were short and limited to a few bivalents. Staging of
      pachytene nuclei based on the morphology of the XY pair with BRCA1 revealed a
      prevalence of early pachytene substages (70.7%) in patients. H2AX was normally
      phosphorylated. CONCLUSIONS: In the absence of the AZFc region, the transient
      zygotene stage is extended, and chromosome condensation is reduced. The low level
      of limited asynapsis, the normal H2AX staining and the incomplete loss of germ
      cells at the pachytene checkpoint indicate that the AZFc region is not critical
      for meiotic recombination. We suggest that the pachytene phenotype develops
      secondarily to a primary defect that influences meiosis.

PMID- 17428879
TI  - Laparoscopy-guided myometrial biopsy in the definite diagnosis of diffuse
      adenomyosis.
AB  - BACKGROUND: The purpose of this study was to investigate the usefulness of
      laparoscopy-guided myometrial biopsy in the diagnosis of diffuse adenomyosis.
      METHODS: This prospective non-randomized study (Canadian Task Force
      classification II-1) was conducted in a tertiary medical center. One hundred
      patients who had clinical signs and symptoms strongly suggestive of adenomyosis
      were included as the study sample. Transvaginal sonography, serum CA-125
      determination and laparoscopy-guided myometrial biopsy were performed. RESULTS:
      The mean largest myometrial thickness was 3.10+/-0.56 cm (range 2.30-4.50). The
      mean serum CA-125 level was 49.64+/-38.30 U/ml (range 10.90-205.28). Of these 100
      patients, adenomyosis was pathologically proven in 92 patients, small leiomyoma
      in four patients and myometrial hypertrophy in four patients. The sensitivity of
      myometrial biopsy was 98% and the specificity 100%; the positive predictive value
      was 100% and the negative predictive value 80%, which were superior to those of
      transvaginal sonography, serum CA-125 determination or the combination of both.
      CONCLUSION: Laparoscopy-guided myometrial biopsy is a valuable tool for obtaining
      a definite diagnosis of diffuse adenomyosis with preservation of the uterus in
      infertility workup or in the evaluation of dysmenorrhea or chronic pelvic pain.

PMID- 17428881
TI  - What variables predict generic and health-related quality of life in a sample of
      Brazilian women experiencing infertility?
AB  - BACKGROUND: Infertility is a condition associated with impairment in several
      areas of life. Questionnaires about quality of life (QoL) allow the examination
      of the impact of health conditions in a broader way, comprehending outcomes
      beyond symptomatology, morbidity and mortality. The aim of this study was to
      identify factors associated with various aspects of QoL. METHODS: Cross-sectional
      study using the following: a socio-demographic and clinical data form, the Health
      Survey Short Form (SF-36) which examines health-related QoL and the WHOQOL-BREF
      which examines general QoL. RESULTS: 177 women seeking fertility assistance were
      interviewed. The sample was predominantly composed of women between 30 and 40
      years old (64%), who had known about their infertility for <5 years (57%) and who
      had had no previous attempts at assisted reproduction (79%). Logistic regression
      indicated the following predictor variables: age (for better general health and
      physical functioning), previous in vitro fertilization (for lower vitality and
      poor psychological health scores), previous reproductive tract surgery (for worse
      general health but higher environment scores), advanced education (for higher
      vitality, mental health and environment scores, but for worse social
      relationships) and perception of worse sexual life (for lower overall scores).
      CONCLUSIONS: The identification of factors associated with better or worse QoL,
      in its different domains, is vital in order to propose and test scientifically
      based interventions on infertile women.

PMID- 17428880
TI  - Osmotic responses and tolerance limits to changes in external osmolalities, and
      oolemma permeability characteristics, of human in vitro matured MII oocytes.
AB  - BACKGROUND: Oocyte cryopreservation remains a realistic objective, provided that
      more systematic approaches are applied, such as thorough analysis of the oocyte
      oolemma permeability to water and diverse cryoprotectants. METHODS: We
      prospectively investigated volume changes over time at different temperatures (30
      degrees C, 22 degrees C and 8 degrees C) of human metaphase II (MII) oocytes
      (obtained in stimulated ICSI cycles and matured in vitro from the germinal
      vesicle stage) when exposed to changes in external osmolality. We also
      investigated human in vitro matured (IVM) oocytes membrane permeability
      characteristics at 22 degrees C to 1,2-propanediol (PG) and dimethylsulphoxide
      (DMSO) and at 30 degrees C, 22 degrees C and 8 degrees C to ethylene glycol (EG),
      and calculated corresponding oocyte oolemma permeability coefficients (Lp and
      Pcpa). Furthermore, we investigated the osmotic tolerance limits of IVM oocytes
      exposed to changes in external osmolality as assessed by their developmental
      competence during the course of 72 h after ICSI. RESULTS: The results of our
      studies describe human oocyte membrane permeability coefficients for EG at 30
      degrees C (2.85+/-0.15x10(-3) cm/min), 22 degrees C (1.17+/-0.60x10(-3) cm/min)
      and 8 degrees C (0.37+/-0.15x10(-3) cm/min). Furthermore, at 22 degrees C the EG
      oolemma permeability coefficient was lower than that of PG and DMSO (1.17+/
      0.60x10(-3) cm/min versus 2.15+/-0.70x10(-3) and 1.56+/-0.38x10(-3) cm/min,
      respectively). Our results also indicate, that human IVM MII oocytes tolerated
      exposure to solutions in the range of 39-2264 mOsmol/kg H2O as assessed by the
      oocytes' developmental competence after exposure. CONCLUSIONS: The results of the
      present study may contribute to a better understanding of the biology and
      cryobiology of human oocytes, and to the design of better and more robust
      cryopreservation (freezing or vitrification) protocols.

PMID- 17428882
TI  - Generation of progeny via ICSI following enrichment of elongated spermatids from
      mouse testis by flow-cytometric cell sorting.
AB  - BACKGROUND: Although ICSI is a useful technique, low elongated spermatid numbers
      frequently causes technical difficulties, especially in the case of azoospermic
      patients. Enrichment of elongated spermatids from the testis prior to ICSI may
      solve this problem. METHODS: To determine whether elongated spermatids had a
      characteristic phenotype suitable for purification, testicular cells prepared
      from 25-day-old mice (from spermatogonia to round spermatids) and adult mice
      (from spermatogonia to elongated spermatids) were compared by flow cytometry.
      After flow-cytometric cell sorting (FCS) based on their side (SSC) and forward
      scatter (FSC), purity of the elongated spermatids in the fractionated population
      was microscopically examined, and functional ability of purified elongated
      spermatids was assessed by ICSI. RESULTS: Elongated spermatids in testicular
      cells showed characteristic SSC and FSC phenotypes. In the purified population,
      approximately 70-80% of the cells were morphologically determined as elongated
      spermatids, in contrast to only 10% before sorting. Using ICSI, purified
      elongated spermatids supported full-term development similar to that of unsorted
      elongated spermatids. Furthermore, we succeeded in enriching the elongated
      spermatids from the infertile testis model by approximately 10-fold. CONCLUSIONS:
      Elongated spermatids with normal developmental ability can be efficiently
      purified by FCS based on SSC and FSC characteristics.

PMID- 17428883
TI  - Mycobacterium avium in the postgenomic era.
AB  - The past several years have witnessed an upsurge of genomic data pertaining to
      the Mycobacterium avium complex (MAC). Despite clear advances, problems with the
      detection of MAC persist, spanning the tests that can be used, samples required
      for their validation, and the use of appropriate nomenclature. Additionally, the
      amount of genomic variability documented to date greatly outstrips the functional
      understanding of epidemiologically different subsets of the organism. In this
      review, we discuss how postgenomic insights into the MAC have helped to clarify
      the relationships between MAC organisms, highlighting the distinction between
      environmental and pathogenic subsets of M. avium. We discuss the availability of
      various genetic targets for accurate classification of organisms and how these
      results provide a framework for future studies of MAC variability. The results of
      postgenomic M. avium study provide optimism that a functional understanding of
      these organisms will soon emerge, with genomically defined subsets that are
      epidemiologically distinct and possess different survival mechanisms for their
      various niches. Although the status quo has largely been to study different M.
      avium subsets in isolation, it is expected that attention to the similarities and
      differences between M. avium organisms will provide greater insight into their
      fundamental differences, including their propensity to cause disease.

PMID- 17428884
TI  - Human protothecosis.
AB  - Human protothecosis is a rare infection caused by members of the genus
      Prototheca. Prototheca species are generally considered to be achlorophyllic
      algae and are ubiquitous in nature. The occurrence of protothecosis can be local
      or disseminated and acute or chronic, with the latter being more common. Diseases
      have been classified as (i) cutaneous lesions, (ii) olecranon bursitis, or (iii)
      disseminated or systemic manifestations. Infections can occur in both
      immunocompetent and immunosuppressed patients, although more severe and
      disseminated infections tend to occur in immunocompromised individuals.
      Prototheca wickerhamii and Prototheca zopfii have been associated with human
      disease. Usually, treatment involves medical and surgical approaches; treatment
      failure is not uncommon. Antifungals such as ketoconazole, itraconazole,
      fluconazole, and amphotericin B are the most commonly used drugs to date. Among
      them, amphotericin B displays the best activity against Prototheca spp. Diagnosis
      is largely made upon detection of characteristic structures observed on
      histopathologic examination of tissue.

PMID- 17428885
TI  - Avian influenza virus (H5N1): a threat to human health.
AB  - Pandemic influenza virus has its origins in avian influenza viruses. The highly
      pathogenic avian influenza virus subtype H5N1 is already panzootic in poultry,
      with attendant economic consequences. It continues to cross species barriers to
      infect humans and other mammals, often with fatal outcomes. Therefore, H5N1 virus
      has rightly received attention as a potential pandemic threat. However, it is
      noted that the pandemics of 1957 and 1968 did not arise from highly pathogenic
      influenza viruses, and the next pandemic may well arise from a low-pathogenicity
      virus. The rationale for particular concern about an H5N1 pandemic is not its
      inevitability but its potential severity. An H5N1 pandemic is an event of low
      probability but one of high human health impact and poses a predicament for
      public health. Here, we review the ecology and evolution of highly pathogenic
      avian influenza H5N1 viruses, assess the pandemic risk, and address aspects of
      human H5N1 disease in relation to its epidemiology, clinical presentation,
      pathogenesis, diagnosis, and management.

PMID- 17428886
TI  - Problems in diagnosing scabies, a global disease in human and animal populations.
AB  - Scabies is a worldwide disease and a major public health problem in many
      developing countries, related primarily to poverty and overcrowding. In remote
      Aboriginal communities in northern Australia, prevalences of up to 50% among
      children have been described, despite the availability of effective chemotherapy.
      Sarcoptic mange is also an important veterinary disease engendering significant
      morbidity and mortality in wild, domestic, and farmed animals. Scabies is caused
      by the ectoparasitic mite Sarcoptes scabiei burrowing into the host epidermis.
      Clinical symptoms include intensely itchy lesions that often are a precursor to
      secondary bacterial pyoderma, septicemia, and, in humans, poststreptococcal
      glomerulonephritis. Although diagnosed scabies cases can be successfully treated,
      the rash of the primary infestation takes 4 to 6 weeks to develop, and thus,
      transmission to others often occurs prior to therapy. In humans, the symptoms of
      scabies infestations can mimic other dermatological skin diseases, and
      traditional tests to diagnose scabies are less than 50% accurate. To aid early
      identification of disease and thus treatment, a simple, cheap, sensitive, and
      specific test for routine diagnosis of active scabies is essential. Recent
      developments leading to the expression and purification of S. scabiei recombinant
      antigens have identified a number of molecules with diagnostic potential, and
      current studies include the investigation and assessment of the accuracy of these
      recombinant proteins in identifying antibodies in individuals with active scabies
      and in differentiating those with past exposure. Early identification of disease
      will enable selective treatment of those affected, reduce transmission and the
      requirement for mass treatment, limit the potential for escalating mite
      resistance, and provide another means of controlling scabies in populations in
      areas of endemicity.

PMID- 17428890
TI  - Simulated natural day lengths synchronize seasonal rhythms of asynchronously born
      male Siberian hamsters.
AB  - Photoperiodism research has relied on static day lengths and abrupt transitions
      between long and short days to characterize the signals that drive seasonal
      rhythms. To identify ecologically relevant critical day lengths and to test the
      extent to which naturally changing day lengths synchronize important
      developmental events, we monitored nine cohorts of male Siberian hamsters
      (Phodopus sungorus) born every 2 wk from 4 wk before to 12 wk after the summer
      solstice in a simulated natural photoperiod (SNP). SNP hamsters born from 4 wk
      before to 2 wk after the solstice underwent rapid somatic and gonadal growth;
      among those born 4-6 wk after the solstice, some delayed puberty by many weeks,
      whereas others manifested early puberty. Hamsters born eight or more weeks after
      the solstice failed to undergo early testicular development. The transition to
      delayed development occurred at long day lengths, which induce early puberty when
      presented as static photoperiods. The first animals to delay puberty may do so
      predominantly on the basis of postnatal decreases in day length, whereas in later
      cohorts, a comparison of postnatal day length to gestational day length may
      contribute to arrested development. Despite differences in timing of birth and
      timing of puberty, autumn gonadal regression and spring gonadal and somatic
      growth occurred at similar calendar dates in all cohorts. Incrementally changing
      photoperiods exert a strong organizing effect on seasonal rhythms by providing
      hamsters with a richer source of environmental timing cues than are available in
      simple static day lengths.

PMID- 17428889
TI  - Antimicrobial resistance in Haemophilus influenzae.
AB  - Haemophilus influenzae is a major community-acquired pathogen causing significant
      morbidity and mortality worldwide. Meningitis and bacteremia due to type b
      strains occur in areas where the protein-conjugated type b vaccine is not in use,
      whereas nontypeable strains are major causes of otitis media, sinusitis, acute
      exacerbations of chronic bronchitis, and pneumonia. Antibiotic resistance in this
      organism is more diverse and widespread than is commonly appreciated. Intrinsic
      efflux resistance mechanisms limit the activity of the macrolides, azalides, and
      ketolides. beta-Lactamase production is highly prevalent worldwide and is
      associated with resistance to ampicillin and amoxicillin. Strains with
      alterations in penicillin binding proteins, particularly PBP3 (beta-lactamase
      negative ampicillin resistant and beta-lactamase positive amoxicillin-clavulanate
      resistant), are increasing in prevalence, particularly in Japan, with increasing
      resistance to ampicillin, amoxicillin, amoxicillin-clavulanate, and many
      cephalosporins, limiting the efficacy of expanded-spectrum cephalosporins against
      meningitis and of many oral cephalosporins against other diseases. Most strains
      remain susceptible to the carbapenems, which are not affected by penicillin
      binding protein changes, and the quinolones. The activity of many oral agents is
      limited by pharmacokinetics achieved with administration by this route, and the
      susceptibility of isolates based on pharmacokinetic and pharmacodynamic
      parameters is reviewed.

PMID- 17428891
TI  - Arginine vasopressin inhibits Kir6.1/SUR2B channel and constricts the mesenteric
      artery via V1a receptor and protein kinase C.
AB  - Kir6.1/SUR2B channel is the major isoform of K(ATP) channels in the vascular
      smooth muscle. Genetic disruption of either subunit leads to dysregulation of
      vascular tone and regional blood flows. To test the hypothesis that the
      Kir6.1/SUR2B channel is a target molecule of arginine vasopressin (AVP), we
      performed studies on the cloned Kir6.1/SUR2B channel and cell-endogenous K(ATP)
      channel in rat mesenteric arteries. The Kir6.1/SUR2B channel was expressed
      together with V1a receptor in the HEK-293 cell line. Whole cell currents of the
      transfected HEK cells were activated by K(ATP) channel opener pinacidil and
      inhibited by K(ATP) channel inhibitor glibenclamide. AVP produced a concentration
      dependent inhibition of the pinacidil-activated currents with IC(50) 2.0 nM. The
      current inhibition was mediated by a suppression of the open-state probability
      without effect on single-channel conductance. An exposure to 100 nM PMA, a potent
      PKC activator, inhibited the pinacidil-activated currents, and abolished the
      channel inhibition by AVP. Such an effect was not seen with inactive phorbol
      ester. A pretreatment of the cells with selective PKC blocker significantly
      diminished the inhibitory effect of AVP. In acutely dissociated vascular smooth
      myocytes, AVP strongly inhibited the cell-endogenous K(ATP) channel. In isolated
      mesenteric artery rings, AVP produced concentration-dependent vasoconstrictions
      with EC(50) 6.5 nM. At the maximum effect, pinacidil completely relaxed
      vasoconstriction in the continuing exposure to AVP. The magnitude of the AVP
      induced vasoconstriction was significantly reduced by calphostin-C. These results
      therefore indicate that the Kir6.1/SUR2B channel is a target molecule of AVP, and
      the channel inhibition involves G(q)-coupled V1a receptor and PKC.

PMID- 17428892
TI  - Effects of corticospinal tract stimulation on renal sympathetic nerve activity in
      rats with intact and chronically lesioned spinal cords.
AB  - Sympathetic preganglionic neurons and interneurons are closely apposed
      (presumably synapsed upon) by corticospinal tract (CST) axons. Sprouting of the
      thoracic CST rostral to lumbar spinal cord injuries (SCI) substantially increases
      the incidence of these appositions. To test our hypothesis that these additional
      synapses would increase CST control of sympathetic activity after SCI, we
      measured the effects of electrical stimulation of the CST on renal sympathetic
      nerve activity (RSNA) and arterial pressure (AP) in alpha-chloralose-anesthetized
      rats with either chronically intact or chronically lesioned spinal cords. Stimuli
      were delivered to the CST at intensities between 25-150 muA and frequencies
      between 25 and 75 Hz. Stimulation of the CST at the midcervical level decreased
      RSNA and AP. These decreases were not mediated by direct projections of the CST
      to the thoracic spinal cord because we could still elicit them by midcervical
      stimulation after acute lesions of the CST at caudal cervical levels. In
      contrast, caudal thoracic CST stimulation increased RSNA and AP. Neither the
      responses to cervical nor thoracic stimulation were affected by chronic lumbar
      SCI. These data show that the CST mediates decreases in RSNA via a cervical
      spinal system but excites spinal sympathetic neurons at caudal thoracic levels.
      Because chronic lumber spinal cord injury affected responses evoked from neither
      the cervical nor thoracic CST, we conclude that lesion-induced or regeneration
      induced formation of new synapses between the CST and sympathetic neurons may not
      affect cardiovascular regulation.

PMID- 17428893
TI  - Restriction of placental function alters heart development in the sheep fetus.
AB  - Placental insufficiency, resulting in restriction of fetal substrate supply, is a
      major cause of intrauterine growth restriction (IUGR) and increased neonatal
      morbidity. Fetal adaptations to placental restriction maintain the growth of key
      organs, including the heart, but the impact of these adaptations on individual
      cardiomyocytes is unknown. Placental and hence fetal growth restriction was
      induced in fetal sheep by removing the majority of caruncles in the ewe before
      mating (placental restriction, PR). Vascular surgery was performed on 13 control
      and 11 PR fetuses at 110-125 days of gestation (term: 150 +/- 3 days). PR fetuses
      with a mean gestational Po(2) < 17 mmHg were defined as hypoxic. At postmortem
      (<135 or >135 days), fetal hearts were collected, and cardiomyocytes were
      isolated and fixed. Proliferating cardiomyocytes were counted by
      immunohistochemistry of Ki67 protein. Cardiomyocytes were stained with methylene
      blue to visualize the nuclei, and the proportion of mononucleated cells and
      length and width of cardiomyocytes were measured. PR resulted in chronic fetal
      hypoxia, IUGR, and elevated plasma cortisol concentrations. Although there was no
      difference in relative heart weights between control and PR fetuses, there was an
      increase in the proportion of mononucleated cardiomyocytes in PR fetuses. Whereas
      mononucleated and binucleated cardiomyocytes were smaller, the relative size of
      cardiomyocytes when expressed relative to heart weight was larger in PR compared
      with control fetuses. The increase in the relative proportion of mononucleated
      cardiomyocytes and the relative sparing of the growth of individual
      cardiomyocytes in the growth-restricted fetus are adaptations that may have long
      term consequences for heart development in postnatal life.

PMID- 17428887
TI  - Helicobacter pylori detection and antimicrobial susceptibility testing.
AB  - The discovery of Helicobacter pylori in 1982 was the starting point of a
      revolution concerning the concepts and management of gastroduodenal diseases. It
      is now well accepted that the most common stomach disease, peptic ulcer disease,
      is an infectious disease, and all consensus conferences agree that the causative
      agent, H. pylori, must be treated with antibiotics. Furthermore, the concept
      emerged that this bacterium could be the trigger of various malignant diseases of
      the stomach, and it is now a model for chronic bacterial infections causing
      cancer. Most of the many different techniques involved in diagnosis of H. pylori
      infection are performed in clinical microbiology laboratories. The aim of this
      article is to review the current status of these methods and their application,
      highlighting the important progress which has been made in the past decade. Both
      invasive and noninvasive techniques will be reviewed.

PMID- 17428894
TI  - Sex differences in monocyte expression of IL-6: role of autonomic mechanisms.
AB  - Sex differences in the prevalence of inflammatory disorders exist, perhaps due to
      sex differences in cellular mechanisms that contribute to proinflammatory
      cytokine activity. This study analyzed sex differences of monocyte intracellular
      expression of IL-6 and its associations with reproductive hormones and autonomic
      mechanisms in 14 matched pairs of men and women (n = 28). Monocyte intracellular
      IL-6 production was repeatedly assessed over two circadian periods. Sympathetic
      balance was estimated by heart rate variability and the ratio of power in the low
      frequency (LF) to high-frequency (HF); vagal tone was indexed by the power of HF
      component. As compared to men, women showed greater monocyte expression of IL-6
      across the circadian period. In addition, women showed lower sympathetic balance
      (LF/HF ratio), and greater levels of vagal tone (HF power). In women, but not
      men, sympathovagal balance was negatively associated with monocyte IL-6
      expression, whereas vagal tone was positively associated with production of this
      cytokine. Levels of reproductive hormones were not related to monocyte IL-6
      expression. The marked increase in monocyte expression of interleukin-6 in women
      has implications for understanding sex differences in risk of inflammatory
      disorders. Additionally, these data suggest that sex differences in sympathovagal
      balance or vagal tone may be a pathway to explain sex differences in IL-6
      expression. Interventions that target autonomic mechanisms might constitute new
      strategies to constrain IL-6 production with impacts on inflammatory disease risk
      in women.

PMID- 17428895
TI  - Paraventricular opioids alter intake of high-fat but not high-sucrose diet
      depending on diet preference in a binge model of feeding.
AB  - Previous work from our laboratory indicates that when rats are given a choice
      between a high-fat and a high-sucrose diet, opioid blockade with naltrexone (NTX)
      in a reward-related site (central amygdala) inhibits intake of the preferred diet
      only, whereas NTX injected into a homeostasis-related site, such as the
      hypothalamic paraventricular nucleus (PVN), inhibits intake of both diets.
      However, other work suggests that opioids increase intake of fat specifically.
      The present study further investigates the role of PVN opioids in food choices
      made by calorically-replete animals. We used a binge model with chow-maintained
      rats given 3-h access to a choice of a high-fat or high-sucrose diet 3 days a
      week. We hypothesized that intra-PVN injection of the mu-opioid agonist, DAMGO
      (0, 0.025, 0.25, and 2.5 nmol) would enhance, and NTX (0, 10, 30, and 100 nmol)
      would inhibit intake of both diets to an equal extent. We found that when animals
      were divided into groups according to sucrose or fat preference, DAMGO increased
      fat intake in fat-consuming animals, while having no effect on intake of either
      diet in sucrose-consuming animals. NTX, however, inhibited fat intake in both
      groups. Intra-PVN NTX did not inhibit intake of sucrose when presented in the
      absence of a fat choice, but did so when injected peripherally. Furthermore,
      intra-PVN and systemic NTX inhibited intake of chow by 24-h-food-deprived
      animals. These results indicate a complex role for PVN opioids in food intake
      with preference, nutrient type, and energy state affecting the ability of these
      compounds to change behavior.

PMID- 17428888
TI  - Epidemiology and control of neosporosis and Neospora caninum.
AB  - Neospora caninum is a protozoan parasite of animals. Until 1988, it was
      misidentified as Toxoplasma gondii. Since its first recognition in dogs in 1984
      and the description of the new genus and species Neospora caninum in 1988,
      neosporosis has emerged as a serious disease of cattle and dogs worldwide.
      Abortions and neonatal mortality are a major problem in livestock operations, and
      neosporosis is a major cause of abortion in cattle. Although antibodies to N.
      caninum have been reported, the parasite has not been detected in human tissues.
      Thus, the zoonotic potential is uncertain. This review is focused mainly on the
      epidemiology and control of neosporosis in cattle, but worldwide seroprevalences
      of N. caninum in animals and humans are tabulated. The role of wildlife in the
      life cycle of N. caninum and strategies for the control of neosporosis in cattle
      are discussed.

PMID- 17428896
TI  - Temporal-spatial expression of ANG-(1-7) and angiotensin-converting enzyme 2 in
      the kidney of normal and hypertensive pregnant rats.
AB  - We recently demonstrated that renin-angiotensin system (RAS) overactivity during
      late gestation in rats is associated with increased kidney and urine levels of
      ANG-(1-7) and enhanced kidney immunostaining of ANG-(1-7) and angiotensin
      converting enzyme 2 (ACE2). To understand the temporal-spatial changes in normal
      and hypertensive pregnancies, the renal distribution of ANG-(1-7) and ACE2 in
      association with kidney angiotensin peptides and ACE2 activity was examined in
      virgin, normal pregnant (NP; gestational days 5, 15, and 19) and reduced uterine
      perfusion pressure (RUPP at day 19) pregnant Sprague-Dawley rats. ANG-(1-7) and
      ACE2 immunocytochemical staining increased 1.8- and 1.9-fold and 1.7- and 1.8
      fold, respectively, at days 15 and 19 of NP, compared with virgin rats. ANG-(1-7)
      and ANG II concentrations were increased in the kidney at 19 days of gestation.
      ACE2 activity measured using a fluorescent substrate was increased 1.9- and 1.9
      fold in the cortex and 1.9- and 1.8-fold in the medulla at days 15 and 19 of NP.
      In the RUPP animals, ANG-(1-7) immunostaining and concentration were
      significantly decreased compared with 19-day NP rats. ACE2 activity was unchanged
      in the cortex and medulla of RUPP rats. In conclusion, during NP, the concurrent
      changes of ACE2 and ANG-(1-7) suggest that ACE2 plays an important role in
      regulating the renal levels of ANG-(1-7) at mid to late gestation. However, the
      decrease in renal ANG-(1-7) content in the absence of a concomitant decrease in
      ACE2 implicates the participation of other ANG-(1-7) forming or degrading enzymes
      during hypertensive pregnancy.

PMID- 17428897
TI  - Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR
      rat lungs.
AB  - Intrauterine growth restriction (IUGR) increases the incidence of chronic lung
      disease (CLD). The molecular mechanisms responsible for IUGR-induced acute lung
      injury that predispose the IUGR infant to CLD are unknown. p53, a transcription
      factor, plays a pivotal role in determining cellular response to stress by
      affecting apoptosis, cell cycle regulation, and angiogenesis, processes required
      for thinning of lung mesenchyme. Because thickened lung mesenchyme is
      characteristic of CLD, we hypothesized that IUGR-induced changes in lung growth
      are associated with alterations in p53 expression and/or modification. We induced
      IUGR through bilateral uterine artery ligation of pregnant rats. Uteroplacental
      insufficiency significantly decreased serine-15-phosphorylated (serine-15P) p53,
      an active form of p53, in IUGR rat lung. Moreover, we found that decreased
      phosphorylation of lung p53 serine-15 localized to thickened distal air space
      mesenchyme. We also found that IUGR significantly decreased mRNA for targets
      downstream of p53, specifically, proapoptotic Bax and Apaf, as well as Gadd45,
      involved in growth arrest, and Tsp-1, involved in angiogenesis. Furthermore, we
      found that IUGR significantly increased mRNA for Bcl-2, an antiapoptotic gene
      downregulated by p53. We conclude that in IUGR rats, uteroplacental insufficiency
      induces decreased lung mesenchymal p53 serine-15P in association with distal lung
      mesenchymal thickening. We speculate that decreased p53 serine-15P in IUGR rat
      lungs alters lung phenotype, making the IUGR lung more susceptible to subsequent
      injury.

PMID- 17428898
TI  - Intermittent intraperitoneal infusion of peptide YY(3-36) reduces daily food
      intake and adiposity in obese rats.
AB  - Peptide YY(3-36) [PYY(3-36)] is a gut-brain peptide that decreases food intake
      when administered by intravenous infusion to lean and obese humans and rats.
      However, chronic administration of PYY(3-36) by osmotic minipump to lean and
      obese rodents produces only a transient reduction in daily food intake and weight
      gain. It has recently been shown that 1-h intravenous infusions of PYY(3-36)
      every other hour for 10 days produced a sustained reduction in daily food intake,
      body weight, and adiposity in lean rats. Here, we determined whether intermittent
      delivery of PYY(3-36) can produce a similar response in diet-induced obese rats.
      During a 21-day period, obese rats (body fat >25%) received twice daily
      intraperitoneal infusion of vehicle (n = 18) or PYY(3-36) (n = 24) during hours 1
      3 and 7-9 of the dark period. Rats had free access to both a 45% fat solid diet
      and a 29% fat liquid diet; intakes were determined from continuous computer
      recording of changes in food container weights. To sustain a 15-25% reduction in
      daily caloric intake, the initial PYY(3-36) dose of 30 pmol.kg(-1).min(-1) was
      reduced to 10 pmol.kg(-1).min(-1) on day 10 and then increased to 17 pmol.kg(
      1).min(-1) on day 13. This dosing strategy produced a sustained reduction in
      daily caloric intake of 11-32% and prevented body weight gain (8 +/- 6 vs. 51 +/-
      11 g) and fat deposition (4.4 +/- 7.6 vs. 41.0 +/- 12.8 g). These results
      indicate that intermittent intraperitoneal infusion of PYY(3-36) can produce a
      sustained reduction in food intake and adiposity in diet-induced obese rodents
      consuming palatable high-fat foods.

PMID- 17428899
TI  - Development of temporal response properties and contrast sensitivity of V1 and V2
      neurons in macaque monkeys.
AB  - The temporal contrast sensitivity of human infants is reduced compared to that of
      adults. It is not known which neural structures of our visual brain sets limits
      on the early maturation of temporal vision. In this study we investigated how
      individual neurons in the primary visual cortex (V1) and visual area 2 (V2) of
      infant monkeys respond to temporal modulation of spatially optimized grating
      stimuli and a range of stimulus contrasts. As early as 2 wk of age, V1 and V2
      neurons exhibited band-pass temporal frequency tuning. However, the optimal
      temporal frequency and temporal resolution of V1 neurons were much lower in 2-
      and 4-wk-old infants than in 8-wk-old infants or adults. V2 neurons of 8-wk-old
      monkeys had significantly lower optimal temporal frequencies and resolutions than
      those of adults. Onset latency was longer in V1 at 2 and 4 wk of age and was
      slower in V2 even at 8 wk of age than in adults. Contrast threshold of V1 and V2
      neurons was substantially higher in 2- and 4-wk-old infants but became adultlike
      by 8 wk of age. For the first 4 wk of life, responses to high-contrast stimuli
      saturated more readily in V2. The present results suggest that although the early
      development of temporal vision and contrast sensitivity may largely depend on the
      functional maturation of precortical structures, it is also likely to be limited
      by immaturities that are unique to V1 and V2.

PMID- 17428900
TI  - Evolution of motor memory during the seconds after observation of motor error.
AB  - When a movement results in error, the nervous system amends the motor commands
      that generate the subsequent movement. Here we show that this adaptation depends
      not just on error, but also on passage of time between the two movements. We
      observed that subjects learned a reaching task faster, i.e., with fewer trials,
      when the intertrial time intervals (ITIs) were lengthened. We hypothesized two
      computational mechanisms that could have accounted for this. First, learning
      could have been driven by a Bayesian process where the learner assumed that
      errors are the result of perturbations that have multiple timescales. In theory,
      longer ITIs can produce faster learning because passage of time might increase
      uncertainty, which in turn increases sensitivity to error. Second, error in a
      trial may result in a trace that decays with time. If the learner continued to
      sample from the trace during the ITI, then adaptation would increase with
      increased ITIs. The two models made separate predictions: The Bayesian model
      predicted that when movements are separated by random ITIs, the learner would
      learn most from a trial that followed a long time interval. In contrast, the
      trace model predicted that the learner would learn most from a trial that
      preceded a long time interval. We performed two experiments to test for these
      predictions and in both experiments found evidence for the trace model. We
      suggest that motor error produces an error memory trace that decays with a time
      constant of about 4 s, continuously promoting adaptation until the next movement.

PMID- 17428901
TI  - Stochastic resonance in the motor system: effects of noise on the monosynaptic
      reflex pathway of the cat spinal cord.
AB  - In sensory systems, the presence of a particular nonzero level of noise may
      significantly enhance the ability of an individual to detect weak sensory stimuli
      through a phenomenon known as stochastic resonance (SR). The aim of this study
      was to demonstrate if such phenomenon is also exhibited by the motor system; in
      particular, in the Ia-motoneuron synapse of the cat spinal cord. Monosynaptic
      reflexes elicited by periodic electrical stimulation to the medial gastrocnemius
      nerve were recorded in the L(7) ventral root (or in single motoneurons) of
      decerebrated cats. Random stretches (mechanical noise) were applied to the
      lateral gastrocnemius plus soleus muscle by means of a closed-loop mechanical
      stimulator-transducer. In all cats, we observed the SR phenomenon. The amplitude
      of the monosynaptic reflexes (or number of action potentials recorded in the
      motoneurons) evoked by the weak electrical stimuli applied to the medial
      gastrocnemius nerve were an inverted U-like function of the mechanical noise
      applied to the lateral gastrocnemius plus soleus muscle. A significant maximum
      value in the amplitude of the monosynaptic responses was reached with a
      particular noise amplitude value. Numerical simulations on a model of the
      monosynaptic reflex pathway qualitatively reproduce this stochastic resonance
      behavior. We conclude that the monosynaptic reflex response elicited by Ia
      afferents is optimized by the noisy stretching of a synergistic muscle. Our study
      provides the first direct demonstration that the motor system, and not only the
      sensory systems, exhibits the SR phenomenon.

PMID- 17428902
TI  - Characterization of voltage-gated ionic channels in cholinergic amacrine cells in
      the mouse retina.
AB  - Recent studies have shown that cholinergic amacrine cells possess unique membrane
      properties. However, voltage-gated ionic channels in cholinergic amacrine cells
      have not been characterized systematically. In this study, using
      electrophysiological and immunohistochemical techniques, we examined voltage
      gated ionic channels in a transgenic mouse line the cholinergic amacrine cells of
      which were selectively labeled with green fluorescent protein (GFP). Voltage
      gated K(+) currents contained a 4-aminopyridine-sensitive current (A current) and
      a tetraethylammonium-sensitive current (delayed rectifier K(+) current). Voltage
      gated Ca(2+) currents contained a omega-conotoxin GVIA-sensitive component (N
      type) and a omega-Aga IVA-sensitive component (P/Q-type). Tetrodotoxin-sensitive
      Na(+) currents and dihydropyridine-sensitive Ca(2+) currents (L-type) were not
      observed. Immunoreactivity for the Na channel subunit (Pan Nav), the K channel
      subunits (the A-current subunits [Kv. 3.3 and Kv 3.4]) and the Ca channel
      subunits (alpha1(A) [P/Q-type], alpha1(B) [N-type] and alpha1(C) [L-type]) was
      detected in the membrane fraction of the mouse retina by Western blot analysis.
      Immunoreactivity for the Kv. 3.3, Kv 3.4, alpha1(A) [P/Q-type], and alpha1(B) [N
      type] was colocalized with the GFP signals. Immunoreactivity for alpha1(C) [L
      type] was not colocalized with the GFP signals. Immunoreactivity for Pan Nav did
      not exist on the membrane surface of the GFP-positive cells. Our findings
      indicate that signal propagation in cholinergic amacrine cells is mediated by a
      combination of two types of voltage-gated K(+) currents (the A current and the
      delayed rectifier K(+) current) and two types of voltage-gated Ca(2+) currents
      (the P/Q-type and the N-type) in the mouse retina.

PMID- 17428903
TI  - Vestibular system may provide equivalent motor actions regardless of the number
      of body segments involved in the task.
AB  - The vestibulospinal system likely plays an essential role in motor equivalence-
      the ability to reach the desired motor goal despite intentional or imposed
      changes in the number of body segments involved in the task. To test this
      hypothesis, we compared the ability of healthy subjects and patients with
      unilateral vestibular lesions (surgical acoustic neuroma resection 0.6 to 6.7 yr
      before the study) to maintain either the same hand position or the same
      trajectory of within arm reach movements while flexing the trunk, in the absence
      of vision. In randomly selected trials, the trunk motion was prevented by an
      electromagnetic device. Healthy subjects were able to preserve the hand position
      or trajectory by modifying the elbow and shoulder joint rotations in a condition
      dependent way, at a minimal latency of about 60 ms after the trunk movement
      onset. In contrast, six of seven patients showed deficits in the compensatory
      angular modifications at least in one of two tasks so that 30-100% of the trunk
      displacement was not compensated and thus influenced the hand position or
      trajectory. Results suggest that vestibular influences evoked by the head motion
      during trunk flexion play a major role in maintaining the consistency of arm
      motor actions in external space despite changes in the number of body segments
      involved. Our findings also suggest that despite long-term plasticity in the
      vestibular system and related neural structures, unilateral vestibular lesion may
      reduce the capacity of the nervous system to achieve motor equivalence.

PMID- 17428904
TI  - Mapping function onto neuronal morphology.
AB  - Neurons have a wide range of dendritic morphologies the functions of which are
      largely unknown. We used an optimization procedure to find neuronal morphological
      structures for two computational tasks: first, neuronal morphologies were
      selected for linearly summing excitatory synaptic potentials (EPSPs); second,
      structures were selected that distinguished the temporal order of EPSPs. The
      solutions resembled the morphology of real neurons. In particular the neurons
      optimized for linear summation electrotonically separated their synapses, as
      found in avian nucleus laminaris neurons, and neurons optimized for spike-order
      detection had primary dendrites of significantly different diameter, as found in
      the basal and apical dendrites of cortical pyramidal neurons. This similarity
      makes an experimentally testable prediction of our theoretical approach, which is
      that pyramidal neurons can act as spike-order detectors for basal and apical
      inputs. The automated mapping between neuronal function and structure introduced
      here could allow a large catalog of computational functions to be built indexed
      by morphological structure.

PMID- 17428905
TI  - Decoding M1 neurons during multiple finger movements.
AB  - We tested several techniques for decoding the activity of primary motor cortex
      (M1) neurons during movements of single fingers or pairs of fingers. We report
      that single finger movements can be decoded with >99% accuracy using as few as 30
      neurons randomly selected from populations of task-related neurons recorded from
      the M1 hand representation. This number was reduced to 20 neurons or less when
      the neurons were not picked randomly but selected on the basis of their
      information content. We extended techniques for decoding single finger movements
      to the problem of decoding the simultaneous movement of two fingers. Movements of
      pairs of fingers were decoded with 90.9% accuracy from 100 neurons. The
      techniques we used to obtain these results can be applied, not only to movements
      of single fingers and pairs of fingers as reported here, but also to movements of
      arbitrary combinations of fingers. The remarkably small number of neurons needed
      to decode a relatively large repertoire of movements involving either one or two
      effectors is encouraging for the development of neural prosthetics that will
      control hand movements.

PMID- 17428906
TI  - Electrophysiological properties and subunit composition of GABAA receptors in
      patients with gelastic seizures and hypothalamic hamartoma.
AB  - Abnormalities in GABA(A) receptor structure and/or function have been associated
      with various forms of epilepsy in both humans and animals. Whether this is true
      for patients with gelastic seizures and hypothalamic hamartoma (HH) is unknown.
      In this study, we characterized the pharmacological properties and native subunit
      composition of GABA(A) receptors on acutely dissociated single neurons from
      surgically resected HH tissues using patch-clamp, immunocytochemical, and RT-PCR
      techniques. We found that 1) GABA induced an inward current (I(GABA)) at a
      holding potential of -60 mV; 2) I(GABA) was mimicked by the GABA(A) receptor
      agonist muscimol and blocked by the GABA(A) receptor antagonist bicuculline,
      suggesting that I(GABA) was mediated principally through the GABA(A) receptor; 3)
      the EC(50) and Hill coefficient derived from the I(GABA) concentration-response
      curve were 6.8 muM and 1.9, respectively; 4) the current-voltage curve was linear
      at a reversal potential close to zero; and 5) I(GABA) exhibited low sensitivity
      to zinc and diazepam but higher sensitivity to pentobarbital and pregnanolone.
      Additionally, using Xenopus oocytes microtransplanted with normal human
      hypothalamic tissue, we confirmed that the functional properties of GABA(A)
      receptors were similar to those seen in small isolated HH neurons. Finally, the
      expression profile of GABA(A) receptor subunits obtained from normal control
      human hypothalamic tissue was identical to that from surgically resected human HH
      tissue. Taken together, our data indicate that GABA(A) receptors on small HH
      neurons exhibit normal pharmacosensitivity and subunit composition. These
      findings bear relevance to a broader understanding of inhibitory
      neurotransmission in human HH tissue.

PMID- 17428907
TI  - HVC neural sleep activity increases with development and parallels nightly
      changes in song behavior.
AB  - Sleep abnormalities are coexpressed with human communication disorders. Recent
      data from the birdsong system, the best model for human speech, indicate that
      sleep has a critical role in vocal learning. To understand the neural mechanisms
      that underlie behavioral changes during sleep, we recorded sleep activity in the
      song control area HVC longitudinally during song development in zebra finches. We
      focused on the sensorimotor phase of song learning, when the finch shapes his
      song behavior toward a learned tutor song model. Direct comparison of sleep
      activity in adults and juveniles revealed that the juvenile HVC has a lower spike
      rate and longer silent periods than the adult. Within individual finches, sleep
      silent periods decreased and spike rate increased with age. We next
      systematically compared neural sleep activity and song behavior. We now report
      that spike rate during sleep was significantly correlated with overnight changes
      in song behavior. Collectively, these data indicate that sleep activity in the
      vocal control area HVC increases with age and may affect song behavior.

PMID- 17428908
TI  - Voltage-sensitive conductances of bushy cells of the Mammalian ventral cochlear
      nucleus.
AB  - Bushy cells in the ventral cochlear nucleus convey firing of auditory nerve
      fibers to neurons in the superior olivary complex that compare the timing and
      intensity of sounds at the two ears and enable animals to localize sound sources
      in the horizontal plane. Three voltage-sensitive conductances allow bushy cells
      to convey acoustic information with submillisecond temporal precision. All bushy
      cells have a low-voltage-activated, alpha-dendrotoxin (alpha-DTX)-sensitive K(+)
      conductance (g(KL)) that was activated by depolarization past -70 mV, was half
      activated at -39.0 +/- 1.7 (SE) mV, and inactivated approximately 60% over 5 s.
      Maximal g(KL) varied between 40 and 150 nS (mean: 80.8 +/- 16.7 nS). An alpha-DTX
      insensitive, tetraethylammonium (TEA)-sensitive, K(+) conductance (g(KH)) was
      activated at voltages positive to -40 mV, was half-activated at -18.1 +/- 3.8 mV,
      and inactivated by 90% over 5 s. Maximal g(KH) varied between 35 and 80 nS (mean:
      58.2 +/- 6.5 nS). A ZD7288-sensitive, mixed cation conductance (g(h)) was
      activated by hyperpolarization greater than -60 mV and half-activated at -83.1 +/
      1.1 mV. Maximum g(h) ranged between 14.5 and 56.6 nS (mean: 30.0 +/- 5.5 nS). 8
      Br-cAMP shifted the voltage sensitivity of g(h) positively. Changes in
      temperature stably altered the steady-state magnitude of I(h). Both g(KL) and
      g(KH) contribute to repolarizing action potentials and to sharpening synaptic
      potentials. Those cells with the largest g(h) and the largest g(KL) fired least
      at the onset of a depolarization, required the fastest depolarizations to fire,
      and tended to be located nearest the nerve root.

PMID- 17428910
TI  - Object category structure in response patterns of neuronal population in monkey
      inferior temporal cortex.
AB  - Our mental representation of object categories is hierarchically organized, and
      our rapid and seemingly effortless categorization ability is crucial for our
      daily behavior. Here, we examine responses of a large number (>600) of neurons in
      monkey inferior temporal (IT) cortex with a large number (>1,000) of natural and
      artificial object images. During the recordings, the monkeys performed a passive
      fixation task. We found that the categorical structure of objects is represented
      by the pattern of activity distributed over the cell population. Animate and
      inanimate objects created distinguishable clusters in the population code. The
      global category of animate objects was divided into bodies, hands, and faces.
      Faces were divided into primate and nonprimate faces, and the primate-face group
      was divided into human and monkey faces. Bodies of human, birds, and four-limb
      animals clustered together, whereas lower animals such as fish, reptile, and
      insects made another cluster. Thus the cluster analysis showed that IT population
      responses reconstruct a large part of our intuitive category structure, including
      the global division into animate and inanimate objects, and further hierarchical
      subdivisions of animate objects. The representation of categories was distributed
      in several respects, e.g., the similarity of response patterns to stimuli within
      a category was maintained by both the cells that maximally responded to the
      category and the cells that responded weakly to the category. These results
      advance our understanding of the nature of the IT neural code, suggesting an
      inherently categorical representation that comprises a range of categories
      including the amply investigated face category.

PMID- 17428909
TI  - Estimates of the location of L-type Ca2+ channels in motoneurons of different
      sizes: a computational study.
AB  - In the presence of monoamines, L-type Ca(2+) channels on the dendrites of
      motoneurons contribute to persistent inward currents (PICs) that can amplify
      synaptic inputs two- to sixfold. However, the exact location of the L-type Ca(2+)
      channels is controversial, and the importance of the location as a means of
      regulating the input-output properties of motoneurons is unknown. In this study,
      we used a computational strategy developed previously to estimate the dendritic
      location of the L-type Ca(2+) channels and test the hypothesis that the location
      of L-type Ca(2+) channels varies as a function of motoneuron size. Compartmental
      models were constructed based on dendritic trees of five motoneurons that ranged
      in size from small to large. These models were constrained by known differences
      in PIC activation reported for low- and high-conductance motoneurons and the
      relationship between somatic PIC threshold and the presence or absence of tonic
      excitatory or inhibitory synaptic activity. Our simulations suggest that L-type
      Ca(2+) channels are concentrated in hotspots whose distance from the soma
      increases with the size of the dendritic tree. Moving the hotspots away from
      these sites (e.g., using the hotspot locations from large motoneurons on
      intermediate-sized motoneurons) fails to replicate the shifts in PIC threshold
      that occur experimentally during tonic excitatory or inhibitory synaptic
      activity. In models equipped with a size-dependent distribution of L-type Ca(2+)
      channels, the amplification of synaptic current by PICs depends on motoneuron
      size and the location of the synaptic input on the dendritic tree.

PMID- 17428911
TI  - Spatial frequency-specific contrast adaptation originates in the primary visual
      cortex.
AB  - Adaptation to a high-contrast grating stimulus causes reduced sensitivity to
      subsequent presentation of a visual stimulus with similar spatial
      characteristics. This behavioral finding has been attributed by
      neurophysiological studies to processes within the visual cortex. However, some
      evidence indicates that contrast adaptation phenomena are also found in early
      visual pathways. Adaptation effects have been reported in retina and lateral
      geniculation nucleus (LGN). It is possible that these early pathways could be the
      physiological origin of the cortical adaptation effect. To study this, we
      recorded from single neurons in the cat's LGN. We find that contrast adaptation
      in the LGN, unlike that in the visual cortex, is not spatial frequency specific,
      i.e., adaptation effects apply to a broad range of spatial frequencies. In
      addition, aside from the amplitude attenuation, the shape of spatial frequency
      tuning curves of LGN cells is not affected by contrast adaptation. Again, these
      findings are unlike those found for cells in the visual cortex. Together, these
      results demonstrate that pattern specific contrast adaptation is a cortical
      process.

PMID- 17428912
TI  - Bilateral vestibular loss in cats leads to active destabilization of balance
      during pitch and roll rotations of the support surface.
AB  - Although the balance difficulties accompanying vestibular loss are well known,
      the underlying cause remains unclear. We examined the role of vestibular inputs
      in the automatic postural response (APR) to pitch and roll rotations of the
      support surface in freely standing cats before and in the first week after
      bilateral labyrinthectomy. Support surface rotations accelerate the body center
      of mass toward the downhill side. The normal APR consists of inhibition in the
      extensors of the uphill limbs and excitation in the downhill limbs to decelerate
      the body and maintain the alignment of the limbs with respect to earth-vertical.
      After vestibular lesion, cats were unstable during rotation perturbations and
      actively pushed themselves downhill rather than uphill, using a postural response
      that was opposite to that seen in the control trials. The extensors of the uphill
      rather than downhill limbs were activated, whereas those of the downhill limbs
      were inhibited rather than being excited. We propose that vestibular inputs
      provide an important reference to earth-vertical, which is critical to computing
      the appropriate postural response during active orientation to the vertical. In
      the absence of this vestibular information, subjects orient to the support
      surface using proprioceptive inputs, which drives the body downhill resulting in
      instability and falling. This is consistent with current models of sensory
      integration for computation of body posture and orientation.

PMID- 17428913
TI  - Fentanyl clearance and volume of distribution are increased in patients with
      major burns.
AB  - This study examined the pharmacokinetics of fentanyl in burned patients during
      the hyperdynamic phase. Twenty adults, aged 37 +/- 2 years (mean +/- SE), with 49
      +/- 3% total body surface area burn, were studied at 17 +/- 2 days after the
      injury and compared to demographically matched controls. After a 200-microg IV
      bolus of fentanyl, blood samples (n = 20) were collected for 4.5 hours.
      Concentration-time curves were fitted to a 2-compartment model. Burned patients
      had a higher cardiac index. Median fentanyl clearance (CL, 21.0 vs 29.4
      mL/kg/min), central compartment volume (V(1), 0.37 vs 0.61 L/kg), and total
      volume of distribution (V(area), 3.6 vs 5.8 L/kg) were higher in burned patients.
      Cardiac index was unrelated to CL. The increased V(1) and V(area) are likely due
      to large intravenous fluid replacement and tissue edema. Higher CL and larger
      V(1) and V(area) leading to a lower fentanyl plasma concentration may partially
      explain the increased opiate requirement previously observed after burn injury.

PMID- 17428915
TI  - Unique germ-line organelle, nuage, functions to repress selfish genetic elements
      in Drosophila melanogaster.
AB  - The nuage is an electron-dense perinuclear structure that is known to be a
      hallmark of animal germ-line cells. Although the conservation of the nuage
      throughout evolution accentuates its essentiality, its role(s) and the exact
      mechanism(s) by which it functions in the germ line still remain unknown. Here,
      we report a nuage component, Krimper (KRIMP), in Drosophila melanogaster and show
      that it ensures the repression of the selfish genetic elements in the female germ
      line. The Krimp loss-of-function allele exhibited female sterility, defects in
      karyosome formation and oocyte polarity, and precocious osk translation. These
      phenotypes are commonly observed in the other nuage component mutants, vasa (vas)
      and maelstrom (mael), and the RNA-silencing component mutants, spindle-E (spn-E)
      and aubergine (aub), suggesting a shared underlying defect that uses RNA
      silencing. Moreover, we demonstrated that the localization of the nuage
      components depends on both SPN-E and AUB and that the selfish genetic elements
      were derepressed to different extents in the nuage component mutants, as well as
      in aub and armitage (armi) mutants. In the nuage component mutants, vas, krimp,
      and mael, the levels of roo, I-element, and HeT-A repeat-associated small
      interfering RNAs were greatly reduced. Hence, our data suggest that the nuage
      functions as a specialized center that protects the genome in the germ-line cells
      via gene regulation mediated by repeat-associated small interfering RNAs.

PMID- 17428914
TI  - Intranuclear targeting and nuclear export of the adenovirus E1B-55K protein are
      regulated by SUMO1 conjugation.
AB  - We have investigated the requirements for CRM1-mediated nuclear export and SUMO1
      conjugation of the adenovirus E1B-55K protein during productive infection. Our
      data show that CRM1 is the major export receptor for E1B-55K in infected cells.
      Functional inactivation of the E1B-55K CRM1-dependent nuclear export signal (NES)
      or leptomycin B treatment causes an almost complete redistribution of the viral
      protein from the cytoplasm to the nucleus and its accumulation at the periphery
      of the viral replication centers. Interestingly, however, this nuclear
      restriction imposed on the wild type and the NES mutant protein is fully
      compensated by concurrent inactivation of the adjacent SUMO1 conjugation site.
      Moreover, the same mutation fully reverses defects of the NES mutant in the
      nucleocytoplasmic transport of Mre11 and proteasomal degradation of p53. These
      results show that nuclear export of E1B-55K in infected cells occurs via CRM1
      dependent and -independent pathways and suggest that SUMO1 conjugation and
      deconjugation provide a molecular switch that commits E1B-55K to a CRM1
      independent export pathway.

PMID- 17428916
TI  - GABAergic inhibition at dendrodendritic synapses tunes gamma oscillations in the
      olfactory bulb.
AB  - In the olfactory bulb (OB), odorants induce oscillations in the gamma range (20
      80 Hz) that play an important role in the processing of sensory information.
      Synaptic transmission between dendrites is a major contributor to this
      processing. Glutamate released from mitral cell dendrites excites the dendrites
      of granule cells, which in turn mediate GABAergic inhibition back onto mitral
      cells. Although this reciprocal synapse is thought to be a key element supporting
      oscillatory activity, the mechanisms by which dendrodendritic inhibition induces
      and maintains gamma oscillations remain unknown. Here, we assessed the role of
      the dendrodendritic inhibition, using mice lacking the GABA(A) receptor alpha1
      subunit, which is specifically expressed in mitral cells but not in granule
      cells. The spontaneous inhibitory postsynaptic current frequency in these mutants
      was low and was consistent with the reduction of GABA(A) receptor clusters
      detected by immunohistochemistry. The remaining GABA(A) receptors in mitral cells
      contained the alpha3-subunit and supported slower decaying currents of unchanged
      amplitude. Overall, inhibitory-mediated interactions between mitral cells were
      smaller and slower in mutant than in WT mice, although the strength of sensory
      afferent inputs remained unchanged. Consequently, both experimental and
      theoretical approaches revealed slower gamma oscillations in the OB network of
      mutant mice. We conclude, therefore, that fast oscillations in the OB circuit are
      strongly constrained by the precise location, subunit composition and kinetics of
      GABA(A) receptors expressed in mitral cells.

PMID- 17428917
TI  - Smallpox subunit vaccine produced in Planta confers protection in mice.
AB  - We report here the in planta production of the recombinant vaccinia virus B5
      antigenic domain (pB5), an attractive component of a subunit vaccine against
      smallpox. The antigenic domain was expressed by using efficient transient and
      constitutive plant expression systems and tested by various immunization routes
      in two animal models. Whereas oral administration in mice or the minipig with
      collard-derived insoluble pB5 did not generate an anti-B5 immune response,
      intranasal administration of soluble pB5 led to a rise of B5-specific
      immunoglobulins, and parenteral immunization led to a strong anti-B5 immune
      response in both mice and the minipig. Mice immunized i.m. with pB5 generated an
      antibody response that reduced virus spread in vitro and conferred protection
      from challenge with a lethal dose of vaccinia virus. These results indicate the
      feasibility of producing safe and inexpensive subunit vaccines by using plant
      production systems.

PMID- 17428918
TI  - Mutant torsinA interferes with protein processing through the secretory pathway
      in DYT1 dystonia cells.
AB  - TorsinA is an AAA(+) protein located predominantly in the lumen of the
      endoplasmic reticulum (ER) and nuclear envelope responsible for early onset
      torsion dystonia (DYT1). Most cases of this dominantly inherited movement
      disorder are caused by deletion of a glutamic acid in the carboxyl terminal
      region of torsinA. We used a sensitive reporter, Gaussia luciferase (Gluc) to
      evaluate the role of torsinA in processing proteins through the ER. In primary
      fibroblasts from controls and DYT1 patients most Gluc activity (95%) was released
      into the media and processed through the secretory pathway, as confirmed by
      inhibition with brefeldinA and nocodazole. Fusion of Gluc to a fluorescent
      protein revealed coalignment and fractionation with ER proteins and association
      of Gluc with torsinA. Notably, fibroblasts from DYT1 patients were found to
      secrete markedly less Gluc activity as compared with control fibroblasts. This
      decrease in processing of Gluc in DYT1 cells appear to arise, at least in part,
      from a loss of torsinA activity, because mouse embryonic fibroblasts lacking
      torsinA also had reduced secretion as compared with control cells. These studies
      demonstrate the exquisite sensitivity of this reporter system for quantitation of
      processing through the secretory pathway and support a role for torsinA as an ER
      chaperone protein.

PMID- 17428919
TI  - Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig
      renders sorting signal in Scap inaccessible to COPII proteins.
AB  - Two classes of sterols, cholesterol and oxysterols, block export of sterol
      regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER)
      to the Golgi by preventing the binding of COPII-coated proteins to a hexapeptide
      sorting signal (MELADL) in Scap, the SREBP-escort protein. Here, we show that
      anti-MELADL blocks COPII binding in vitro, and microinjection of Fab anti-MELADL
      blocks Scap.SREBP movement in cells. Cholesterol and oxysterols block COPII
      binding to MELADL by binding to different intracellular receptors, cholesterol to
      Scap and oxysterols to Insig. Cysteine labeling shows that both binding events
      produce a conformational change near the MELADL sequence, abrogating COPII
      binding but not anti-MELADL binding. Mutagenesis experiments raise the
      possibility that the distance of MELADL from the ER membrane is crucial for COPII
      binding, and we speculate that sterols and Insig block SREBP transport by
      altering the location of MELADL with respect to the membrane, rendering it
      inaccessible to COPII proteins.

PMID- 17428921
TI  - Optimal prediction and the rate of decay for solutions of the Euler equations in
      two and three dimensions.
AB  - The "t-model" for dimensional reduction is applied to the estimation of the rate
      of decay of solutions of the Burgers equation and of the Euler equations in two
      and three space dimensions. The model was first derived in a statistical
      mechanics context, but here we analyze it purely as a numerical tool and prove
      its convergence. In the Burgers case, the model captures the rate of decay
      exactly, as was previously shown. For the Euler equations in two space
      dimensions, the model preserves energy as it should. In three dimensions, we find
      a power law decay in time and observe a temporal intermittency.

PMID- 17428920
TI  - Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi:
      oxysterols block transport by binding to Insig.
AB  - Cholesterol synthesis in animals is controlled by the regulated transport of
      sterol regulatory element-binding proteins (SREBPs) from the endoplasmic
      reticulum to the Golgi, where the transcription factors are processed
      proteolytically to release active fragments. Transport is inhibited by either
      cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by
      binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor
      proteins called Insigs. Here, we show that oxysterols act by binding to Insigs,
      causing Insigs to bind to Scap. Mutational analysis of the six transmembrane
      helices of Insigs reveals that the third and fourth are important for Insig's
      binding to oxysterols and to Scap. These studies define Insigs as oxysterol
      binding proteins, explaining the long-known ability of oxysterols to inhibit
      cholesterol synthesis in animal cells.

PMID- 17428922
TI  - HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex
      vivo and peculiar cytotoxic T lymphocyte activation phenotype.
AB  - Some rare HIV-1-infected individuals, referred to as HIV controllers (HIC), have
      persistently undetectable plasma viral load in the absence of therapy. This
      control of HIV-1 replication has been associated with a strong, multifunctional
      specific CD8(+) T cell response. However, no direct link between this immune
      response and the control of viremia has so far been provided. We investigated
      parameters of specific CD8(+) T cell response and in vitro susceptibility to HIV
      1 infection in 11 HIC. We found high frequencies of HIV-specific CD8(+) T cells.
      Interestingly, these cells expressed the activation marker HLA-DR but not CD38.
      This unique phenotype differentiates HIV-specific CD8(+) T cells from HIC and
      noncontroller subjects and likely reflects a high potential to expand upon
      exposure to antigen and a capacity to exert effector functions. Accordingly,
      although CD4(+) T cells from HIC were fully susceptible to HIV-1 superinfection,
      their CD8(+) T cells effectively suppressed HIV-1 infection. Remarkably, this
      potent anti-HIV activity was observed without prior stimulation of CD8(+) T
      cells. This activity was not mediated by secreted inhibitory factors but was due
      to the elimination of infected CD4(+) T cells and was observed only with
      autologous CD4(+) T cells, indicating an HLA-restricted cytotoxic mechanism. This
      constitutive antiviral capacity of CD8(+) T cells could account for the control
      of viral replication in HIC.

PMID- 17428923
TI  - Discovery of a small molecule antagonist of the parathyroid hormone receptor by
      using an N-terminal parathyroid hormone peptide probe.
AB  - Once-daily s.c. administration of either human parathyroid hormone (PTH)-(1-84)
      or recombinant human PTH-(1-34) provides for dramatic increases in bone mass in
      women with postmenopausal osteoporosis. We initiated a program to discover orally
      bioavailable small molecule equivalents of these peptides. A traditional high
      throughput screening approach using cAMP activation of the PTH/PTH-related
      peptide receptor (PPR) as a readout failed to provide any lead compounds.
      Accordingly, we designed a new screen for this receptor that used a modified N
      terminal fragment of PTH as a probe for small molecule binding to the
      transmembrane region of the PPR, driven by the assumption that the
      pharmacological properties (agonist/antagonist) of compounds that bound to this
      putative signaling domain of the PPR could be altered by chemical modification.
      We developed DPC-AJ1951, a 14 amino acid peptide that acts as a potent agonist of
      the PPR, and characterized its activity in ex vivo and in vivo assays of bone
      resorption. In addition, we studied its ability to initiate gene transcription by
      using microarray technology. Together, these experiments indicated that the
      highly modified 14 amino acid peptide induces qualitatively similar biological
      responses to those produced by PTH-(1-34), albeit with lower potency relative to
      the parent peptide. Encouraged by these data, we performed a screen of a small
      compound collection by using DPC-AJ1951 as the ligand. These studies led to the
      identification of the benzoxazepinone SW106, a previously unrecognized small
      molecule antagonist for the PPR. The binding of SW106 to the PPR was rationalized
      by using a homology receptor model.

PMID- 17428924
TI  - How sterols regulate protein sorting and traffic.

PMID- 17428925
TI  - Organized structures, memory, and the decay of turbulence.

PMID- 17428926
TI  - Evaluation of three molecular assays for rapid identification of methicillin
      resistant Staphylococcus aureus.
AB  - One home-developed assay and two commercial assays for the rapid identification
      of methicillin-resistant Staphylococcus aureus (MRSA) were compared by use of a
      collection of clinical isolates displaying highly diverse genetic backgrounds.
      Our results suggest that users of orfX-staphylococcal cassette chromosome mec
      based assays should repeatedly monitor the local epidemiology to minimize the
      risks of detection bias and the omission of emerging MRSA clones.

PMID- 17428927
TI  - Nocardial cerebral abscess associated with mycetoma, pneumonia, and
      membranoproliferative glomerulonephritis.
AB  - Nocardial brain abscesses remain a clinical challenge. We successfully treated a
      patient with nocardial brain abscess, mycetoma, pneumonia, and
      glomerulonephritis. Nocardial soft tissue involvement, mycetoma, is well known.
      However, the fact that actinomycetoma can metastasize may not be as well
      appreciated. The association between nocardiosis and glomerulonephritis should be
      better clarified.

PMID- 17428928
TI  - Analysis of the first Australian strains of Bartonella quintana reveals unique
      genotypes.
AB  - Bartonella quintana is increasingly recognized as a cause of clinical disease in
      various geographical locations. We characterized three Australian strains
      associated with endocarditis, using established molecular-typing techniques, the
      16S/23S rRNA intergenic spacer (ITS) region, and multispacer typing (MST). All
      strains examined demonstrated novel ITS and/or MST genotypes. Further
      characterization of Australian strains is required to determine whether there is
      an association between genotype and geographical location.

PMID- 17428929
TI  - Evaluation of molecular typing methods in characterizing a European collection of
      epidemic methicillin-resistant Staphylococcus aureus strains: the HARMONY
      collection.
AB  - We analyzed a representative sample of methicillin-resistant Staphylococcus
      aureus (MRSA) from 11 European countries (referred to as the HARMONY collection)
      using three molecular typing methods used within the HARMONY group to examine
      their usefulness for large, multicenter MRSA surveillance networks that use these
      different laboratory methodologies. MRSA isolates were collected based on their
      prevalence in each center and their genetic diversity, assessed by pulsed-field
      gel electrophoresis (PFGE). PFGE groupings (< or = 3 bands difference between
      patterns) were compared to those made by sequencing of the variable repeats in
      the protein A gene spa and clonal designations based on multilocus sequence
      typing (MLST), combined with PCR analysis of the staphylococcal chromosome
      cassette containing the mec genes involved in methicillin resistance (SCCmec). A
      high level of discrimination was achieved using each of the three methodologies,
      with discriminatory indices between 89.5% and 91.9% with overlapping 95%
      confidence intervals. There was also a high level of concordance of groupings
      made using each method. MLST/SCCmec typing distinguished 10 groups containing at
      least two isolates, and these correspond to the majority of nosocomial MRSA
      clones described in the literature. PFGE and spa typing resolved 34 and 31
      subtypes, respectively, within these 10 MRSA clones, with each subtype differing
      only slightly from the most common pattern using each method. The HARMONY group
      has found that the methods used in this study differ in their availability and
      affordability to European centers involved in MRSA surveillance. Here, we
      demonstrate that the integration of such technologies is achievable, although
      common protocols (such as we have developed for PFGE) may also be important, as
      is the use of centralized Internet sites to facilitate data analysis. PFGE and
      spa-typing data from analysis of MRSA isolates from the many centers that have
      access to the relevant equipment can be compared to reference patterns/sequences,
      and clonal designations can be made. In the majority of cases, these will
      correspond to those made by the (more expensive) method of choice-MLST/SCCmec
      typing-and these alternative methods can therefore be used as frontline typing
      systems for multicenter surveillance of MRSA.

PMID- 17428931
TI  - Clinical evaluation of the Sensititre YeastOne plate for testing susceptibility
      of filamentous fungi to posaconazole.
AB  - Sensititre YeastOne colorimetric antifungal panels were compared with the CLSI
      (formerly NCCLS) M38-A reference method for testing the susceptibility of
      filamentous fungi to posaconazole; agreement (+/-2 log2 dilutions) between the
      two methods was 97%. These data confirm the utility of YeastOne panels for
      measuring the susceptibility of filamentous fungi to posaconazole.

PMID- 17428930
TI  - Multiplexed identification of blood-borne bacterial pathogens by use of a novel
      16S rRNA gene PCR-ligase detection reaction-capillary electrophoresis assay.
AB  - We have developed a novel high-throughput PCR-ligase detection reaction-capillary
      electrophoresis (PCR-LDR-CE) assay for the multiplexed identification of 20 blood
      borne pathogens (Staphylococcus epidermidis, Staphylococcus aureus, Bacillus
      cereus, Enterococcus faecalis, Enterococcus faecium, Listeria monocytogenes,
      Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae,
      Escherichia coli, Klebsiella pneumoniae, Haemophilus influenzae, Pseudomonas
      aeruginosa, Acinetobacter baumannii, Neisseria meningitidis, Bacteroides
      fragilis, Bacillus anthracis, Yersinia pestis, Francisella tularensis, and
      Brucella abortus), the last four of which are biothreat agents. The method relies
      on the amplification of two regions within the bacterial 16S rRNA gene, using
      universal PCR primers and querying the identity of specific single-nucleotide
      polymorphisms within the amplified regions in a subsequent LDR. The ligation
      products vary in color and size and are separated by CE. Each organism generates
      a specific pattern of ligation products, which can be used to distinguish the
      pathogens using an automated software program we developed for that purpose. The
      assay has been verified on 315 clinical isolates and demonstrated a detection
      sensitivity of 98%. Additionally, 484 seeded blood cultures were tested, with a
      detection sensitivity of 97.7%. The ability to identify geographically variant
      strains of the organisms was determined by testing 132 isolates obtained from
      across the United States. In summary, the PCR-LDR-CE assay can successfully
      identify, in a multiplexed fashion, a panel of 20 blood-borne pathogens with high
      sensitivity and specificity.

PMID- 17428932
TI  - Multicenter evaluation of a new disk agar diffusion method for susceptibility
      testing of filamentous fungi with voriconazole, posaconazole, itraconazole,
      amphotericin B, and caspofungin.
AB  - The purpose of this study was to correlate inhibition zone diameters, in
      millimeters (agar diffusion disk method), with the broth dilution MICs or minimum
      effective concentrations (MECs) (CLSI M38-A method) of five antifungal agents to
      identify optimal testing guidelines for disk mold testing. The following disk
      diffusion testing parameters were evaluated for 555 isolates of the molds Absidia
      corymbifera, Aspergillus sp. (five species), Alternaria sp., Bipolaris spicifera,
      Fusarium sp. (three species), Mucor sp. (two species), Paecilomyces lilacinus,
      Rhizopus sp. (two species), and Scedosporium sp. (two species): (i) two media
      (supplemented Mueller-Hinton agar [2% dextrose and 0.5 microg/ml methylene blue]
      and plain Mueller-Hinton [MH] agar), (ii) three incubation times (16 to 24, 48,
      and 72 h), and (iii) seven disks (amphotericin B and itraconazole 10-microg
      disks, voriconazole 1- and 10-microg disks, two sources of caspofungin 5-microg
      disks [BBL and Oxoid], and posaconazole 5-microg disks). MH agar supported better
      growth of all of the species tested (24 to 48 h). The reproducibility of zone
      diameters and their correlation with either MICs or MECs (caspofungin) were
      superior on MH agar (91 to 100% versus 82 to 100%; R, 0.71 to 0.93 versus 0.53 to
      0.96 for four of the five agents). Based on these results, the optimal testing
      conditions for mold disk diffusion testing were (i) plain MH agar; (ii)
      incubation times of 16 to 24 h (zygomycetes), 24 h (Aspergillus fumigatus, A.
      flavus, and A. niger), and 48 h (other species); and (iii) the posaconazole 5
      microg disk, voriconazole 1-microg disk, itraconazole 10-microg disk (for all
      except zygomycetes), BBL caspofungin 5-microg disk, and amphotericin B 10-microg
      (zygomycetes only).

PMID- 17428933
TI  - Bronchoalveolar lavage galactomannan in diagnosis of invasive pulmonary
      aspergillosis among solid-organ transplant recipients.
AB  - We review the experience at our institution with galactomannan (GM) testing of
      bronchoalveolar lavage (BAL) fluid in the diagnosis of invasive pulmonary
      aspergillosis (IPA) among solid-organ transplant recipients. Among 81 patients
      for whom BAL GM testing was ordered (heart, 24; kidney, 22; liver, 19; lung, 16),
      there were five cases of proven or probable IPA. All five patients had BAL GM of
      > or = 2.1 and survived following antifungal therapy. The sensitivity,
      specificity, and positive and negative predictive values for BAL GM testing at a
      cutoff of > or = 1.0 were 100%, 90.8%, 41.7%, and 100%, respectively. The
      sensitivity of BAL GM testing was better than that of conventional tests such as
      serum GM or BAL cytology and culture. Moreover, a positive BAL GM test diagnosed
      IPA several days to 4 weeks before other methods for three patients. Twelve
      patients had BAL GM of > or = 0.5 but no evidence of IPA. Among these, lung
      transplant recipients accounted for 41.7% (5/12) of the false-positive results,
      reflecting frequent colonization of airways in this population. Excluding lung
      transplants, the specificity and positive predictive value for other solid-organ
      transplants increased to 92.9% and 62.5%, respectively (cutoff, > or = 1.0). In
      conclusion, BAL GM testing facilitated more-rapid diagnoses of IPA and the
      institution of antifungal therapy among non-lung solid-organ transplant
      recipients and helped to rule out IPA.

PMID- 17428934
TI  - Genetic relatedness of Streptococcus pneumoniae isolates from paired blood and
      respiratory specimens.
AB  - To assess the relatedness of Streptococcus pneumoniae isolates recovered
      concurrently from blood and respiratory tract specimens from patients with
      pneumonia, we analyzed 24 paired isolates by pulsed-field gel electrophoresis
      (PFGE), serotyping, and antimicrobial susceptibility testing. PFGE, serotype,
      and/or susceptibility patterns were identical for 22 of 24 pairs. Susceptibility
      results for blood isolates should guide therapy.

PMID- 17428935
TI  - Evaluation of moxalactam with the BD phoenix system for detection of methicillin
      resistance in coagulase-negative staphylococci.
AB  - The performance of moxalactam with the BD Phoenix system for the detection of
      methicillin resistance in coagulase-negative staphylococci was evaluated by use
      of a collection of 186 strains. Moxalactam was a better drug as an indicator of
      methicillin resistance for mecA-positive strains than oxacillin and cefoxitin
      were. For strains other than Staphylococcus saprophyticus, a moxalactam MIC >16
      microg/ml was indicative of methicillin resistance.

PMID- 17428936
TI  - Comparison of the phenotyping methods ID 32E and VITEK 2 compact GN with 16S rRNA
      gene sequencing for the identification of Enterobacter sakazakii.
AB  - A total of 34 isolates (28 Enterobacter sakazakii and 6 Enterobacteriaceae) from
      infant formulae, milk powder, and the production environment of milk powder
      factories were identified using ID 32E and VITEK 2 compact GN systems
      (bioMerieux, France). The ID 32E version 3.0 and VITEK 2 compact GN version
      01.01b correctly identified 100% (28) of the Enterobacter sakazakii isolates
      tested, whereas the previous software version 2.0 for ID 32E showed only 71.4%
      correct results. None of the non-E. sakazakii isolates tested were misidentified
      as E. sakazakii with either of the identification systems used.

PMID- 17428937
TI  - Peptoniphilus gorbachii sp. nov., Peptoniphilus olsenii sp. nov., and
      Anaerococcus murdochii sp. nov. isolated from clinical specimens of human origin.
AB  - Three groups of previously unknown gram-positive, anaerobic, coccus-shaped
      bacteria were characterized using phenotypic and molecular taxonomic methods.
      Phenotypic and genotypic data demonstrate that these organisms are distinct, and
      each group represents a previously unknown subline within Clostridium cluster
      XIII. Two groups are most closely related to Peptoniphilus harei in the genus
      Peptoniphilus, and the other group is most closely related to Anaerococcus
      lactolyticus in the genus Anaerococcus. Based on the findings, three novel
      species, Peptoniphilus gorbachii sp. nov., Peptoniphilus olsenii sp. nov., and
      Anaerococcus murdochii sp. nov., are proposed. The type strains of Peptoniphilus
      gorbachii sp. nov., Peptoniphilus olsenii sp. nov., and Anaerococcus murdochii
      sp. nov. are WAL 10418(T) (= CCUG 53341(T) = ATCC BAA-1383(T)), WAL 12922(T) (=
      CCUG 53342(T) = ATCC BAA-1384(T)), and WAL 17230(T) (= CCUG 53340(T) = ATCC BAA
      1385(T)), respectively.

PMID- 17428938
TI  - Comparison of tests for detection of beta-lactamase-producing staphylococci.
AB  - Penicillin resistance identification tests are important in veterinary medicine.
      Six enzyme assays and a PCR test were compared for the detection of beta
      lactamase production or the beta-lactamase gene in 175 staphylococcal isolates.
      We conclude that the PCR test and two nitrocefin-based assays can be recommended
      for routine clinical use.

PMID- 17428939
TI  - PCR-restriction fragment length polymorphism for rapid, low-cost identification
      of isoniazid-resistant Mycobacterium tuberculosis.
AB  - PCR-restriction fragment length poymorphism (PCR-RFLP) is a simple, robust
      technique for the rapid identification of isoniazid-resistant Mycobacterium
      tuberculosis. One hundred consecutive isolates from a Vietnamese tuberculosis
      hospital were tested by MspA1I PCR-RFLP for the detection of isoniazid-resistant
      katG_315 mutants. The test had a sensitivity of 80% and a specificity of 100%
      against conventional phenotypic drug susceptibility testing. The positive and
      negative predictive values were 1 and 0.86, respectively. None of the discrepant
      isolates had mutant katG_315 codons by sequencing. The test is cheap (less than
      $1.50 per test), specific, and suitable for the rapid identification of isoniazid
      resistance in regions with a high prevalence of katG_315 mutants among isoniazid
      resistant M. tuberculosis isolates.

PMID- 17428940
TI  - Outbreak of fungemia among neonates caused by Candida haemulonii resistant to
      amphotericin B, itraconazole, and fluconazole.
AB  - The first outbreak of Candida haemulonii fungemia is described. The seven
      isolates from the blood of four neonates were identified by DNA sequencing of the
      ribosomal DNA. They were all resistant to amphotericin B, fluconazole, and
      itraconazole. This report highlights the emergence of C. haemulonii as an
      opportunistic pathogen in immunocompromised patients.

PMID- 17428941
TI  - Comparative genomics of Canadian epidemic lineages of methicillin-resistant
      Staphylococcus aureus.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen that has
      disseminated throughout Canadian hospitals and communities. Pulsed-field gel
      electrophoresis of over 9,300 MRSA isolates obtained from the Canadian Nosocomial
      Infection Surveillance Program has identified 10 epidemic strain types in Canada
      (CMRSA1 to CMRSA10). In an attempt to determine specific genetic factors that
      have contributed to their high prevalence in community and/or hospital settings,
      the genomic content of representative isolates for each of the 10 Canadian
      epidemic types was compared using comparative genomic hybridizations. Comparison
      of the community-associated Canadian epidemic isolates (CMRSA7 and CMRSA10) with
      the hospital-associated Canadian epidemic isolates revealed one open reading
      frame (ORF) (SACOL0046) encoding a putative protein belonging to a metallo-beta
      lactamase family, which was present only in the community-associated Canadian
      epidemic isolates. A more restricted comparison involving only the most common
      hospital-associated Canadian epidemic isolates (CMRSA1 and CMRSA2) with the
      community-associated Canadian epidemic isolates did reveal additional factors
      that might be contributing to their prevalence in the community and hospital
      settings, which included ORFs encoding potential virulence factors involved in
      capsular biosynthesis, serine proteases, epidermin, adhesion factors, regulatory
      functions, leukotoxins, and exotoxins.

PMID- 17428942
TI  - Performance of a rapid assay (Binax NOW) for detection of respiratory syncytial
      virus at a children's hospital over a 3-year period.
AB  - A rapid assay, Binax NOW RSV, was compared to viral culture for 14,756 pediatric
      respiratory specimens obtained from 2003 to 2006. There were 794 viral culture
      confirmed respiratory syncytial virus infections. Sensitivity was 81%, and
      specificity was 93.2%. Sensitivity was greatest for neonates (91.1% versus 80.7%
      [P < 0.01]).

PMID- 17428943
TI  - Rapid and reliable method for quantification of Mycobacterium paratuberculosis by
      use of the BACTEC MGIT 960 system.
AB  - A simple method for the enumeration of viable Mycobacterium paratuberculosis
      cells was developed and evaluated using the MGIT 960 culture system. For each of
      12 M. paratuberculosis strains isolated from either cattle or humans, single-cell
      suspensions of M. paratuberculosis cells were adjusted to an optical density at
      600 nm of 1.00 (10(7.6) to 10(8.2) cells/ml), and serial dilutions were prepared.
      Standard curves were established by relating the MGIT time-to-detection data to
      the log10 CFU for these suspensions using standard plate counting and BACTEC 460
      results as reference methods. Universal and strain-specific standard
      quantification curves were generated. A one-phase exponential decay equation best
      fit the universal standard curve and strain-specific curves (R2 of 0.96 and
      >0.99, respectively). Two subgroups within the universal curves were
      distinguished: one for laboratory-adapted strains and the other for recently
      isolated low-passage bovine strains. The predictive errors for log(10)
      estimations using the universal standard curve, each subgroup's standard curve,
      and strain-specific curves were +/-0.87, +/-0.45, and +/-0.31 log10 units,
      respectively. CFU estimations by all three standard curves were highly
      reproducible, regardless of the M. paratuberculosis strain or inoculum volume. In
      comparison with the previously described BACTEC 460 M. paratuberculosis counting
      method, quantification with MGIT 960 was less expensive, more rapid, more
      accurate, and more sensitive (<10 CFU). This MGIT counting method has broad
      applications for studies requiring the quantification of viable M.
      paratuberculosis cells, such as drug susceptibility testing or environmental
      survival studies.

PMID- 17428944
TI  - Identification and distribution of Mycobacterium leprae genotypes in a region of
      high leprosy prevalence in China: a 3-year molecular epidemiological study.
AB  - Multiple-locus variable-number tandem-repeat (VNTR) analysis (MLVA) has been
      proposed as a means of strain typing for tracking the transmission of leprosy.
      However, empirical data for a defined population are lacking. To this end, a
      study was initiated to assess the diversity and distribution of prevalent
      Mycobacterium leprae strains in Qiubei County, Yunnan Province, People's Republic
      of China, where the annual detection rate of leprosy is 10-fold higher than the
      national average rate. Sixty-eight newly diagnosed leprosy patients were included
      in the study. MLVA at eight M. leprae loci was applied using DNA extracts from
      skin biopsies. The number of alleles per locus ranged from 4 to 24, providing
      adequate strain discrimination. MLVA strain typing identified several clusters of
      patients whose M. leprae specimens shared similar VNTR profiles. Two of these
      clusters were comprised of patients who resided predominantly in the north and
      northwest parts of Qiubei County. Furthermore, it was found that multicase
      families are common in this county: 23 of the 68 patients were from 11 families.
      Intrafamilial VNTR profiles closely matched within six families, although they
      were different between the families. Moreover, VNTR patterns related to those
      found in some multicase families were also detected in patients in the same or
      adjacent townships, indicating the utility of VNTR strain typing to identify and
      detect short-range transmission events. Social contact through village markets is
      proposed as a means of transmission.

PMID- 17428945
TI  - Prevalence of PCR ribotypes among Clostridium difficile isolates from pigs,
      calves, and other species.
AB  - PCR ribotypes were obtained for 144 Clostridium difficile isolates from neonatal
      pigs. Porcine isolates comprised four PCR ribotypes, but one, ribotype 078,
      predominated (83%). This was also the most common ribotype (94%) among 33 calf
      isolates but was rarely identified in other species.

PMID- 17428946
TI  - Improved immunogenicity of a vaccination regimen combining a DNA vaccine encoding
      Brucella melitensis outer membrane protein 31 (Omp31) and recombinant Omp31
      boosting.
AB  - In the present study, we report an attempt to improve the immunogenicity of the
      Omp31 antigen by a DNA prime-protein boost immunization regimen. We immunized
      BALB/c mice with an Omp31 DNA vaccine (pCIOmp31) followed by boosting with
      recombinant Omp31 (rOmp31) in incomplete Freund's adjuvant and characterized the
      resulting immune responses and the protective efficacy against Brucella ovis and
      B. melitensis infection. Immunoglobulin G1 (IgG1) and IgG2a titers were higher in
      sera from pCIOmp31/rOmp31-immunized mice than in sera from mice immunized with
      pCIOmp31 or rOmp31 alone. Splenocytes from pCIOmp31/rOmp31-immunized mice
      produced significantly higher levels of gamma interferon than did those from mice
      given rOmp31 alone. In contrast, interleukin 2 (IL-2) production levels were
      comparable between the two groups of immunized mice. Cells from all immunized
      mice produced undetectable levels of IL-4. Notably, rOmp31 stimulated IL-10
      production in the pCIOmp31/rOmp31-immunized group but not in the pCIOmp31- or
      rOmp31-immunized group. Although the prime-boost regimen induced specific
      cytotoxic responses, these responses could not reach the levels achieved by the
      pCIOmp31 immunization. In conclusion, pCIOmp31 priming followed by rOmp31
      boosting led to moderately improved protection against a challenge with B. ovis
      or B. melitensis.

PMID- 17428948
TI  - Treatment failure related to intrathecal immunoglobulin M (IgM) synthesis,
      cerebrospinal fluid IgM, and interleukin-10 in patients with hemolymphatic-stage
      sleeping sickness.
AB  - Human African trypanosomiasis treatment is stage dependent, but the tests used
      for staging are controversial. Central nervous system involvement and its
      relationship with suramin treatment failure were assessed in 60 patients with
      parasitologically confirmed hemolymphatic-stage Trypanosoma brucei gambiense
      infection (white blood cell count of <or=5/microl and no trypanosomes in the
      cerebrospinal fluid [CSF]). The prognostic value of CSF interleukin-10,
      immunoglobulin M (IgM; as determined by nephelometry and the point-of-care
      LATEX/IgM test), total protein, and trypanosome-specific antibody was assessed.
      The IgM and interleukin-10 levels in serum were measured; and the presence of
      neurological signs, intrathecal IgM synthesis, and blood-CSF barrier dysfunction
      was determined. After suramin treatment, 14 of 60 patients had relapses (23%).
      Relapses were significantly correlated with intrathecal IgM synthesis (odds ratio
      [OR], 46; 95% confidence interval [CI], 8 to 260), a CSF IgM concentration of
      >or=1.9 mg/liter (OR, 11.7; 95% CI, 2.7 to 50), a CSF end titer by the LATEX/IgM
      assay of >or=2 (OR, 10.4; 95% CI, 2.5 to 44), and a CSF interleukin-10
      concentration of >10 pg/ml (OR, 5; 95% CI, 1.3 to 20). The sensitivities of these
      markers for treatment failure ranged from 43 to 79%, and the specificities ranged
      from 74 to 93%. The results show that T. brucei gambiense-infected patients who
      have signs of neuroinflammation in CSF and who are treated with drugs recommended
      for use at the hemolymphatic stage are at risk of treatment failure. This
      highlights the need for the development and the evaluation of accurate point-of
      care tests for the staging of human African trypanosomiasis.

PMID- 17428949
TI  - Noninferiority of antibody response to human papillomavirus type 16 in subjects
      vaccinated with monovalent and quadrivalent L1 virus-like particle vaccines.
AB  - The incorporation of multiple antigens into a single human papillomavirus (HPV)
      vaccine may induce immune interference. To evaluate whether interference occurs
      when HPV type 16 (HPV16) virus-like particles are combined in a multivalent
      vaccine, we conducted a study to evaluate anti-HPV16 responses among subjects
      receiving three-dose regimens of either a monovalent HPV16 vaccine or a
      quadrivalent HPV (types 6, 11, 16, and 18) vaccine.

PMID- 17428950
TI  - Performance of two commercial immunochromatographic assays for rapid detection of
      antibodies specific to human immunodeficiency virus types 1 and 2 in serum and
      urine samples in a rural community-based research setting (Rakai, Uganda).
AB  - Rapid detection of human immunodeficiency virus (HIV) antibodies is of great
      importance in developing and developed countries to diagnose HIV infections
      quickly and at low cost. In this study, two new immunochromatographic rapid tests
      for the detection of HIV antibodies (Aware HIV-1/2 BSP and Aware HIV-1/2 U;
      Calypte Biomedical Corporation) were evaluated in rural Africa to determine the
      tests' performance and comparability to commercially available conventional
      enzyme immunoassay (EIA) and Western blot (WB) tests. This prospective study was
      conducted from March 2005 through May 2005 using serum and urine from respondents
      in the Rakai Community Cohort Survey. Nine hundred sixty-three serum samples were
      tested with the Aware blood rapid assay (Aware-BSP) and compared to two
      independent EIAs for HIV plus confirmatory Calypte WB for any positive EIAs. The
      sensitivity of Aware-BSP was 98.2%, and the specificity was 99.8%. Nine hundred
      forty-two urine samples were run using the Aware urine assay (Aware-U) and linked
      to blood sample results for analysis. The sensitivity of Aware-U was 88.7% and
      specificity was 99.9% compared to blood EIAs confirmed by WB analysis. These
      results support the adoption of the Aware-BSP rapid test as an alternative to EIA
      and WB assays for the diagnosis of HIV in resource-limited settings. However, the
      low sensitivity of the Aware-U assay with its potential for falsely negative HIV
      results makes the urine assay less satisfactory.

PMID- 17428947
TI  - Transcriptional activation of interferon-stimulated genes but not of cytokine
      genes after primary infection of rhesus macaques with dengue virus type 1.
AB  - Macaques are the only animal model used to test dengue virus (DENV) vaccine
      candidates. Nevertheless, the pathogenesis of DENV in macaques is not well
      understood. In this work, by using Affymetrix oligonucleotide microarrays, we
      studied the broad transcriptional modifications and cytokine expression profile
      after infecting rhesus macaques with DENV serotype 1. Five days after infection,
      these animals produced a potent, innate antiviral immune response by inducing the
      transcription of signature genes from the interferon (IFN) pathway with
      demonstrated antiviral activity, such as myxoprotein, 2',5'-oligoadenylate
      synthetase, phospholipid scramblase 1, and viperin. Also, IFN regulatory element
      7, IFN-stimulated gene 15, and protein ligases linked to the ISGylation process
      were up-regulated. Unexpectedly, no up-regulation of IFN-alpha, -beta, or -gamma
      genes was detected. Transcription of the genes of interleukin-10 (IL-10), IL-8,
      IL-6, and tumor necrosis factor alpha was neither up-regulated nor down
      regulated. Results were confirmed by real-time PCR and by multiplex cytokine
      detection in serum samples.

PMID- 17428951
TI  - Production and evaluation of reagents for detection of Histoplasma capsulatum
      antigenuria by enzyme immunoassay.
AB  - The detection of urinary Histoplasma capsulatum polysaccharide antigen (HPA) by
      enzyme immunoassay (EIA) has proven useful for the presumptive diagnosis of
      histoplasmosis in AIDS patients. Assay limitations include (i) detection of a
      largely uncharacterized antigen and (ii) difficulty in reproducibly generating
      antibodies for use in the EIA. To improve antibody production for use in this
      test and to better understand the antigen being detected, we compared rabbit
      antibodies elicited using various immunization schedules, routes, and H.
      capsulatum-derived antigens. Antibodies were evaluated by EIA for their ability
      to detect purified H. capsulatum C antigen (C-Ag) and antigenuria. Reported as
      enzyme immunoassay (EI) units (the A(450) with antigen divided by the A(450)
      without antigen), results demonstrated that intravenous immunization of rabbits
      with whole, killed yeast-phase cells (yeast-i.v. regimen) produced antibodies
      giving the highest EI values in the C-Ag EIA (mean EI units +/- standard
      deviation, 14.9 +/- 0.6 versus 6.4 +/- 0.4 for rabbits immunized with C-Ag versus
      2.4 +/- 0.3 for all other regimens combined). Yeast-i.v. antibodies were highly
      sensitive for the detection of antigenuria in patients with histoplasmosis, as
      shown by the following results: 12/12 patients compared to 10/12, 6/12, 3/12, and
      3/12, respectively, for antibodies from rabbits immunized with (i) C-Ag; (ii)
      whole, killed yeast-phase cells administered subcutaneously and intramuscularly;
      (iii) yeast-phase culture filtrates; and (iv) HPA-positive urine. Rabbits
      immunized using the yeast-i.v. regimen also gave higher peak antibody titers than
      rabbits immunized by any other regimen (P < 0.03), and their antibodies were most
      comparable in reactivity to antibodies produced for use in the standard HPA-EIA
      test (P < 0.001). Therefore, rabbits immunized using the yeast-i.v. regimen
      produced the most sensitive antibodies with the highest titers for detection of C
      Ag and antigenuria in histoplasmosis patients.

PMID- 17428952
TI  - Use of protein-specific monoclonal antibody-based latex agglutination for rapid
      diagnosis of Burkholderia pseudomallei infection in patients with community
      acquired septicemia.
AB  - A latex agglutination test employing monoclonal antibody specific to a 30-kDa
      protein of Burkholderia pseudomallei was used to detect the organisms in blood
      culture specimens from 1,139 patients with community-acquired septicemia. The
      sensitivity, specificity, and positive and negative predictive values of the test
      were 96.75%, 99.61%, 96.75%, and 99.61%, respectively.

PMID- 17428953
TI  - Evaluation of an enzyme immunoassay for detection of immunoglobulin M antibodies
      to West Nile virus and the importance of background subtraction in detecting
      nonspecific reactivity.
AB  - Since the introduction of West Nile virus (WNV) in the United States in 1999,
      several assays have become commercially available to detect antibodies against
      WNV. Capture enzyme-linked immunosorbent assays (ELISAs) for the detection of WNV
      specific immunoglobulin M (IgM) have been approved by the Food and Drug
      Administration for clinical testing and are available from Focus Diagnostics and
      PanBio, Inc. The Focus Diagnostics IgM capture ELISA utilizes a background
      subtraction protocol in order to detect nonspecific reactivity due to rheumatoid
      factor, heterophile antibodies, or other interfering substances. A background
      subtraction procedure is not currently recommended for the PanBio IgM capture
      ELISA. In previous experiments, we determined the agreement, sensitivity, and
      specificity of the PanBio first-generation IgM capture ELISA compared to an
      immunofluorescence assay and the Centers for Disease Control and Prevention's IgM
      capture ELISA. The PanBio assay has since been reformulated to improve the
      specificity of the assay. We evaluated the reformulated PanBio assay with and
      without an antigen subtraction procedure and compared the results to the Focus
      IgM capture ELISA. Agreement, sensitivity, and specificity of the PanBio assay
      were, respectively, 85%, 95%, and 76% without the subtraction protocol and 94%,
      95%, and 93% with the subtraction protocol. In general, when the subtraction
      protocol was applied to the PanBio IgM capture ELISA, there was a reduction in
      some, but not all, false-positive results. We suggest that all WNV IgM assays be
      standardized with a procedure such as background subtraction to eliminate
      nonspecific reactivity that may cause false-positive results.

PMID- 17428954
TI  - Walt Disney World, clinical practice, and scholarly journals.

PMID- 17428955
TI  - Prologue: understanding children who have been affected by maltreatment and
      prenatal alcohol exposure.
AB  - This prologue introduces an important topic for multiple disciplines involved
      with children and their families. This introduction includes a review of some of
      the current literature on the effects of maltreatment and prenatal alcohol
      exposure on child development, an explanation of why this topic is essential
      learning for communication professionals, prevalence figures for the occurrence
      of these effects, and a summarization of the articles that have been contributed
      by a cross section of researchers from various disciplines.

PMID- 17428956
TI  - Neurobiology and neurodevelopmental impact of childhood traumatic stress and
      prenatal alcohol exposure.
AB  - PURPOSE: Research reveals that prenatal alcohol exposure and child trauma (i.e.,
      abuse, neglect, sexual abuse) can have deleterious effects on child development
      across multiple domains. This study analyzed the impact on childhood
      neurodevelopment of prenatal alcohol exposure and postnatal traumatic experience
      compared to postnatal traumatic experience alone. Although the harmful effects of
      both have been well documented individually, there is no research documenting the
      concurrent effects of prenatal alcohol exposure and postnatal trauma on a child's
      developmental process. METHOD: Transdisciplinary assessment of the children
      included the core disciplines of medicine, speech-language pathology,
      occupational therapy, social work, and psychology. Medical examination,
      standardized developmental and intelligence testing, projective tools, parent
      questionnaires, and psychosocial interviews provided information in the primary
      developmental areas. RESULTS: Findings indicated that children who had been
      exposed prenatally to alcohol along with postnatal traumatic experience had lower
      intelligence scores and more severe neurodevelopmental deficits in language,
      memory, visual processing, motor skills, and attention than did traumatized
      children without prenatal alcohol exposure, as well as greater
      oppositional/defiant behavior, inattention, hyperactivity, impulsivity, and
      social problems. CLINICAL IMPLICATIONS: Successful teacher and speech-language
      pathologist interventions with traumatized children with prenatal alcohol
      exposure demand a paradigm shift that requires the development of new
      perspectives and ongoing training.

PMID- 17428957
TI  - Sensory modulation disorders among children with a history of trauma: a frame of
      reference for speech-language pathologists.
AB  - PURPOSE: The purpose of this article is to present definitions and concepts about
      sensory modulation, illustrate behavioral aspects of sensory modulation
      disorders, describe a framework for assessment and intervention, and present
      advances in research. METHOD: A review of descriptive and evidence-based
      literature related to the impact of exposure to both prenatal and postnatal
      trauma on sensory modulation is provided, with additional information gleaned
      from recent assessment data on children with a history of trauma who are served
      by the Southwest Michigan Children's Trauma Assessment Center (CTAC). CLINICAL
      IMPLICATIONS: The review of the literature indicates support for the presence of
      sensory modulation disorders among traumatized children. In addition, the
      emerging data now being gathered on children who have been assessed by CTAC
      indicate a significant prevalence of sensory modulation disorders among children
      with a history of trauma alone, and those with both trauma and a diagnosis of
      fetal alcohol spectrum disorder (FASD). Awareness, recognition, and
      identification of behaviors associated with this disorder, and referral to
      appropriate professionals, is essential to ensure effective preventive and
      intervention services.

PMID- 17428958
TI  - A state of double jeopardy: impact of prenatal alcohol exposure and adverse
      environments on the social communicative abilities of school-age children with
      fetal alcohol spectrum disorder.
AB  - PURPOSE: This article is a retrospective examination of environmental risk,
      language performance, and narrative discourse data from a clinical database of
      school-age children with fetal alcohol spectrum disorder (FASD). METHOD: A case
      defined diagnostic approach for measuring and reporting the full spectrum of
      disabilities in children with prenatal alcohol exposure is presented.
      Demographic, environmental, language, and social communication (as reflected by
      narrative discourse) data are reported for a large cohort of children with FASD
      between the ages of 6;0 (years;months) and 12;0. RESULTS: Children with FASD are
      a heterogeneous group with varying levels of compromise. The data demonstrate a
      substantial comorbidity between the effects of prenatal alcohol exposure and
      adverse caregiving environments. The data further reveal that school-age children
      with FASD often exhibit clinically meaningful deficits in language and social
      communication. CLINICAL IMPLICATION: Children with FASD may be particularly
      vulnerable to language and social communication deficits as a result of prenatal
      alcohol exposure and atypical or adverse social interactive experiences.
      Comprehensive assessment is recommended. Dynamic and functional assessment
      paradigms may document the language and social communicative deficits in children
      with FASD and other clinical populations with complex neurodevelopmental
      profiles.

PMID- 17428959
TI  - Understanding alexithymia and language skills in children: implications for
      assessment and intervention.
AB  - PURPOSE: This article reviews the construct of alexithymia and its relationship
      to language impairment. METHOD: The article includes a review of the literature
      on emotional competence, trauma effects, alexithymia, and language impairment;
      summarizes tools to assess alexithymia; and provides an intervention framework.
      IMPLICATIONS: Understanding the relationship of emotional competence and language
      impairment may provide a new perspective for speech-language pathologists who are
      serving children with language and socioemotional impairments.

PMID- 17428960
TI  - Child maltreatment: a global issue.
AB  - PURPOSE: This article explains why children with speech and language impairments
      are at increased risk for having experienced abuse, neglect, and trauma and how
      maltreatment may vary across cultures. METHOD: International literature on
      maltreatment is reviewed in order to provide frameworks for identifying what
      constitutes maltreatment across cultures; how cultural variations in discipline
      practices impact maltreatment; and professionals' roles in treatment when they
      encounter children who have experienced abuse, neglect, or trauma. CONCLUSION:
      Speech-language pathologists and audiologists are required to document and report
      any instance of suspected child abuse. To intervene effectively with children and
      families from diverse cultures who experience maltreatment, professionals must
      understand when a practice causes harm and be able to modify childrearing
      practices in culturally acceptable ways.

PMID- 17428961
TI  - Collaborative services: children experiencing neglect and the side effects of
      prenatal alcohol exposure.
AB  - PURPOSE: The purpose of this article is to provide critical knowledge regarding
      children who are served by the child welfare system and how these children's
      specialized needs affect speech-language services. Specifically, the structure of
      social services system models is presented, with an emphasis on the cultural and
      systemic interactions between service providers and families. In addition, the
      role of special education for children who have experienced abuse, neglect, and
      prenatal drug or alcohol exposure is presented, with an emphasis on social
      service and special education legal issues. METHOD: This article provides a
      critical analysis of the research literature to date regarding effective tools
      for providing collaborative intervention to children who are experiencing fetal
      alcohol syndrome disorder or abuse and/or neglect. CLINICAL IMPLICATIONS: This
      article provides suggestions about the collaborative roles that speech-language
      pathologists should integrate into treatment milieu when delivering therapy to
      children with histories of abuse, neglect, and prenatal drug or alcohol exposure.

PMID- 17428962
TI  - Epilogue: understanding children who have been affected by maltreatment and
      prenatal alcohol exposure: future directions.
AB  - This epilogue summarizes the six articles presented in the clinical forum focused
      on understanding children who have been affected by maltreatment and prenatal
      alcohol exposure. It presents common themes that emerged among the articles and
      future research directions.

PMID- 17428963
TI  - Sonic hedgehog carried by microparticles corrects endothelial injury through
      nitric oxide release.
AB  - Microparticles (MPs) are small fragments generated from the plasma membrane after
      cell stimulation. Among the candidate proteins harbored by MPs, we recently
      showed that sonic hedgehog (Shh) is present in MPs generated from
      activated/apoptotic human T lymphocytes [Martinez et al., Blood (2006) vol. 108,
      3012-3020]. We show here that Shh carried by MPs induces nitric oxide (NO)
      release from endothelial cells, triggers changes in the expression and
      phosphorylation of enzymes related to the NO pathway, and decreases production of
      reactive oxygen species. When PI3-kinase and ERK signaling were specifically
      inhibited, the effects of MPs were reversed. In vivo injection of MPs in mice was
      also able to improve endothelial function by increasing NO release, and it
      reversed endothelial dysfunction after ischemia/reperfusion. Silencing the
      effects of Shh with cyclopamine, a specific inhibitor of Shh, or siRNA, an
      inhibitor of the Shh receptor Patched, strongly reduced production of NO elicited
      by MPs. Taken together, we propose that the biological message carried by MPs
      harboring Shh may represent a new therapeutic approach against endothelial
      dysfunction during acute severe endothelial injury.

PMID- 17428964
TI  - HGF attenuates thrombin-induced endothelial permeability by Tiam1-mediated
      activation of the Rac pathway and by Tiam1/Rac-dependent inhibition of the Rho
      pathway.
AB  - Reorganization of the endothelial cell (EC) cytoskeleton and cell adhesive
      complexes provides a structural basis for increased vascular permeability
      implicated in the pathogenesis of many diseases, including asthma, sepsis, and
      acute respiratory distress syndrome (ARDS). We have recently described the
      barrier-protective effects of hepatocyte growth factor (HGF) on the human
      pulmonary EC. In the present study, we explored the involvement of Rac-GTPase and
      Rac-specific nucleotide exchange factor Tiam1 in the mechanisms of EC barrier
      protection by HGF. HGF protected EC monolayers from thrombin-induced
      hyperpermeability, disruption of intercellular junctions, and formation of stress
      fibers and paracellular gaps by inhibiting thrombin-induced activation of Rho
      GTPase, Rho association with nucleotide exchange factor p115-RhoGEF, and myosin
      light chain phosphorylation, which was opposed by stimulation of Rac-dependent
      signaling. The pharmacological Rac inhibitor or silencing RNA (siRNA) based
      depletion of either Rac or Tiam1 significantly attenuated HGF-induced peripheral
      translocation of Rac effector cortactin, cortical actin ring formation, and EC
      barrier enhancement. Moreover, Tiam1 knockdown using the siRNA approach,
      attenuated the protective effect of HGF against thrombin-induced activation of
      Rho signaling, monolayer disruption, and EC hyperpermeability. This study
      demonstrates the Tiam1/Rac-dependent mechanism of HGF-induced EC barrier
      protection and provides novel mechanistic insights into regulation of EC
      permeability via dynamic interactions between Rho- and Tiam1/Rac-mediated
      pathways.

PMID- 17428965
TI  - A role for presenilin in post-stress regulation: effects of presenilin mutations
      on Ca2+ currents in Drosophila.
AB  - It has been shown that presenilin is involved in maintaining Ca2+ homeostasis in
      neurons, including regulating endoplasmic reticulum (ER) Ca2+ storage. From
      studies of primary cultures and cell lines, however, its role in stress-induced
      responses is still controversial. In the present study we analyzed the effects of
      presenilin mutations on membrane currents and synaptic functions in response to
      stress using an in vivo preparation. We examined voltage-gated K+ and Ca2+
      currents at the Drosophila larval neuromuscular junction (NMJ) with voltage-clamp
      recordings. Our data showed that both currents were generally unaffected by loss
      of-function or Alzheimer's disease (AD) -associated presenilin mutations under
      normal or stress conditions induced by heat shock (HS) or ER stress. In larvae
      expressing the mutant presenilins, prolonged Ca2+ tail current, reflecting slower
      deactivation kinetics of Ca2+ channels, was observed 1 day after stress
      treatments were terminated. It was further demonstrated that the L-type Ca2+
      channel was specifically affected under these conditions. Moreover, synaptic
      plasticity at the NMJ was reduced in larvae expressing the mutant presenilins. At
      the behavioral level, memory in adult flies was impaired in the presenilin
      mutants 1 day after HS. The results show that presenilin function is important
      during the poststress period and its impairment contributes to memory dysfunction
      observed during adaptation to normal conditions after stress. Our findings
      suggest a new stress-related mechanism by which presenilin may be implicated in
      the neuropathology of AD.

PMID- 17428966
TI  - A single route to action? The common representation of perceptual and saccade
      targets.

PMID- 17428967
TI  - Amygdala neurons differentially encode motivation and reinforcement.
AB  - Lesion studies demonstrate that the basolateral amygdala complex (BLA) is
      important for assigning motivational significance to sensory stimuli, but little
      is known about how this information is encoded. We used in vivo electrophysiology
      procedures to investigate how the amygdala encodes motivating and reinforcing
      properties of cues that induce reinstatement of reward-seeking behavior. Two
      groups of rats were trained to respond to a sucrose reward. The "paired" group
      was trained with a reward-predictive cue, whereas the "unpaired" group was
      trained with a randomly presented cue. Both groups underwent identical extinction
      and reinstatement procedures during which the reward was withheld. The proportion
      of neurons that were phasically cue responsive during reinstatement was
      significantly higher in the paired group (46 of 100) than in the unpaired group
      (8 of 112). Cues that induce reward-seeking behavior can do so by acting as
      incentives or reinforcers. Distinct populations of neurons responded to the cue
      in trials in which the cue acted as an incentive, triggering a motivated reward
      seeking state, or as a reinforcer, supporting continued instrumental responding.
      The incentive motivation-encoding population of neurons (34 of 46 cue-responsive
      neurons; 74%) extinguished in temporal agreement with a decrease in the rate of
      instrumental responding. The conditioned reinforcement-encoding population of
      neurons (12 of 46 cue-responsive neurons; 26%) maintained their response for the
      duration of cue-reinforced instrumental responding. These data demonstrate that
      separate populations of cue-responsive neurons in the BLA encode the motivating
      or reinforcing properties of a cue previously associated with a reward.

PMID- 17428968
TI  - Hypoxia suppresses glutamate transport in astrocytes.
AB  - Glutamate uptake by astrocytes is fundamentally important in the regulation of
      CNS function. Disruption of uptake can lead to excitotoxicity and is implicated
      in various neurodegenerative processes as well as a consequence of
      hypoxic/ischemic events. Here, we investigate the effect of hypoxia on activity
      and expression of the key glutamate transporters excitatory amino acid
      transporter 1 (EAAT1) [GLAST (glutamate-aspartate transporter)] and EAAT2 [GLT-1
      (glutamate transporter 1)]. Electrogenic, Na+-dependent glutamate uptake was
      monitored via whole-cell patch-clamp recordings from cortical astrocytes. Under
      hypoxic conditions (2.5 and 1% O2 exposure for 24 h), glutamate uptake was
      significantly reduced, and pharmacological separation of uptake transporter
      subtypes suggested that the EAAT2 subtype was preferentially reduced relative to
      the EAAT1. This suppression was confirmed at the level of EAAT protein expression
      (via Western blots) and mRNA levels (via real-time PCR). These effects of hypoxia
      to inhibit glutamate uptake current and EAAT protein levels were not replicated
      by desferrioxamine, cobalt, FG0041, or FG4496, agents known to mimic effects of
      hypoxia mediated via the transcriptional regulator, hypoxia-inducible factor
      (HIF). Furthermore, the effects of hypoxia were not prevented by topotecan, which
      prevents HIF accumulation. In stark contrast, inhibition of nuclear factor-kappaB
      (NF-kappaB) with SN50 fully prevented the effects of hypoxia on glutamate uptake
      and EAAT expression. Our results indicate that prolonged hypoxia can suppress
      glutamate uptake in astrocytes and that this effect requires activation of NF
      kappaB but not of HIF. Suppression of glutamate uptake via this mechanism may be
      an important contributory factor in hypoxic/ischemic triggered glutamate
      excitotoxicity.

PMID- 17428969
TI  - Anti-GM1 antibodies cause complement-mediated disruption of sodium channel
      clusters in peripheral motor nerve fibers.
AB  - Voltage-gated Na+ (Na(v)) channels are highly concentrated at nodes of Ranvier in
      myelinated axons and facilitate rapid action potential conduction. Autoantibodies
      to gangliosides such as GM1 have been proposed to disrupt nodal Nav channels and
      lead to Guillain-Barre syndrome, an autoimmune neuropathy characterized by acute
      limb weakness. To test this hypothesis, we examined the molecular organization of
      nodes in a disease model caused by immunization with gangliosides. At the acute
      phase with progressing limb weakness, Na(v) channel clusters were disrupted or
      disappeared at abnormally lengthened nodes concomitant with deposition of IgG and
      complement products. Paranodal axoglial junctions, the nodal cytoskeleton, and
      Schwann cell microvilli, all of which stabilize Na(v) channel clusters, were also
      disrupted. The nodal molecules disappeared in lesions with complement deposition
      but no localization of macrophages. During recovery, complement deposition at
      nodes decreased, and Na(v) channels redistributed on both sides of affected
      nodes. These results suggest that Na(v) channel alterations occur as a
      consequence of complement-mediated disruption of interactions between axons and
      Schwann cells. Our findings support the idea that acute motor axonal neuropathy
      is a disease that specifically disrupts the nodes of Ranvier.

PMID- 17428970
TI  - Beta-catenin regulates acetylcholine receptor clustering in muscle cells through
      interaction with rapsyn.
AB  - Agrin is believed to be a factor used by motoneurons to direct acetylcholine
      receptor (AChR) clustering at the neuromuscular junction. However, exactly how
      agrin mediates this effect remains unclear. Here we demonstrate that the beta
      catenin interacts with rapsyn, a molecule key for AChR clustering. Agrin
      stimulation increases the association of beta-catenin with surface AChRs.
      Suppression of beta-catenin expression inhibited agrin-induced AChR clustering,
      suggesting a necessary role of beta-catenin in this event. The beta-catenin
      action did not appear to require the function of T-cell factors (TCFs),
      suggesting a mechanism independent of TCF-mediated transcription. In contrast,
      prevention of beta-catenin from interacting with alpha-catenin attenuated agrin
      induced AChR clustering. These results suggest that beta-catenin may serve as a
      link between AChRs and alpha-catenin-associated cytoskeleton, revealing a novel
      function of beta-catenin in synaptogenesis.

PMID- 17428971
TI  - Temporal dissociation between hand shaping and grip force scaling in the anterior
      intraparietal area.
AB  - In humans, both clinical and functional imaging studies have evidenced the
      critical role played by the posterior parietal cortex, and particularly by the
      anterior intraparietal area (AIP), in skilled hand movements. However, the exact
      contribution of AIP to precision grasping remains debated. Here we used
      transcranial magnetic stimulation (TMS) to induce virtual lesions of the left
      and/or right AIP in subjects performing a grip-lift task with either hand. We
      found that, during movement preparation, a virtual lesion of AIP had distinct
      consequences on precision grasping of either hand depending on its time of
      occurrence: TMS applied 270-220 ms before the fingers contacted the manipulandum
      altered specifically the hand shaping, whereas lesions induced 170-120 ms before
      contact time only affected the grip force scaling. The lateralization of these
      two processes in AIP is also strikingly different: whereas a bilateral lesion of
      AIP was necessary to impair hand shaping, only a unilateral lesion of the left
      AIP altered the grip force scaling in either hand. The present study shows that,
      during movement preparation, AIP is responsible for processing two distinct,
      temporally dissociated, precision grasping parameters, regardless of the hand in
      use. This indicates that the contribution of AIP to hand movements is "effector
      independent," a finding that may explain the invariance of grasping movements
      performed with either hand.

PMID- 17428972
TI  - 2-Aminoethoxydiphenylborane is an acute inhibitor of directly photosensitive
      retinal ganglion cell activity in vitro and in vivo.
AB  - The mammalian retina contains directly photosensitive retinal ganglion cells
      (RGCs), which use the photopigment melanopsin. The generation of mice lacking
      melanopsin has been invaluable in elucidating the function of these cells. These
      animals display deficiencies in circadian photoentrainment, the pupil light
      reflex, and the circadian regulation of the cone pathway. Interpreting the
      results from such gene knock-out models is always complicated by neuronal
      plasticity and the potential for restructuring of neuronal networks. Until now,
      the study of photosensitive RGCs has lacked an acute inhibitor. 2
      Aminoethoxydiphenylborane (2-APB) is an antagonist at IP3 receptors and an
      inhibitor of canonical transient receptor potential ion channels (TRPCs). Here,
      we show that 2-APB is an extremely potent in vitro inhibitor of the
      photosensitive RGCs and that its effect is independent of store-dependent Ca2+
      release. The identification of canonical TRPC6 and TRPC7 ion channels in
      melanopsin-expressing ganglion cells suggests that 2-APB may act directly on a
      TRPC ion channel. Importantly, using the pupil light reflex as a functional
      assay, we show that 2-APB inhibits photosensitive RGC activity in vivo.
      Collectively, our data further elucidate the phototransduction pathway in the
      photosensitive RGCs and demonstrate that 2-APB can be used to silence activity in
      these cells both in vitro and in vivo.

PMID- 17428973
TI  - Short-term plasticity of kainate receptor-mediated EPSCs induced by NMDA
      receptors at hippocampal mossy fiber synapses.
AB  - Kainate receptors (KARs) are heteromeric ionotropic glutamate receptors that play
      a variety of functions in the regulation of the activity of synaptic networks.
      Little is known about the regulation of the function of synaptic KARs in the
      brain. In the present study, we found that a conditioning activation of synaptic
      NMDA receptors (NMDARs) induces short-term depression of KAR-EPSCs but not of
      AMPA receptor-EPSCs at synapses between mossy fibers and CA3 pyramidal cells.
      Short-term depression of KAR-EPSCs by synaptic NMDARs peaked at 1 s and reversed
      within 20 s, was likely induced and expressed postsynaptically, and was
      homosynaptic. It depended on a rise of Ca2+ in the postsynaptic cell and on the
      activation of the phosphatase calcineurin that likely binds to the GluR6b
      (glutamate receptor subunit 6b) subunit splice variant allowing the
      dephosphorylation of KARs and inhibition of activity. Finally, we show in the
      current-clamp mode that short-term depression of KAR-EPSPs is induced by the
      coincident discharge of action potentials in the postsynaptic cell together with
      synaptic stimulation. Hence, this study describes a form of short-term synaptic
      plasticity that is postsynaptic, depends on the temporal order of presynaptic and
      postsynaptic spiking, and likely affects the summation properties of mossy fiber
      EPSPs.

PMID- 17428974
TI  - Amygdala damage impairs eye contact during conversations with real people.
AB  - The role of the human amygdala in real social interactions remains essentially
      unknown, although studies in nonhuman primates and studies using photographs and
      video in humans have shown it to be critical for emotional processing and suggest
      its importance for social cognition. We show here that complete amygdala lesions
      result in a severe reduction in direct eye contact during conversations with real
      people, together with an abnormal increase in gaze to the mouth. These novel
      findings from real social interactions are consistent with an hypothesized role
      for the amygdala in autism and the approach taken here opens up new directions
      for quantifying social behavior in humans.

PMID- 17428975
TI  - Conditioned dopamine release in humans: a positron emission tomography
      [11C]raclopride study with amphetamine.
AB  - Studies in laboratory rodents suggest that previously neutral stimuli repeatedly
      paired with the administration of drugs of abuse can acquire the ability to
      increase striatal dopamine release. This conditioned neurochemical response is
      believed to prompt drug seeking in animals and has been hypothesized to
      contribute to drug craving and relapse in substance abusers. In the present
      study, we used positron emission tomography and [11C]raclopride to investigate
      whether amphetamine-predictive stimuli can elicit striatal dopamine release in
      humans. Nine healthy male volunteers received a capsule containing amphetamine
      tablets (0.3 mg/kg) on three separate occasions approximately every other day
      (mean +/- SD, 2.25 +/- 1.13 d apart) in the same environment (scanner suite). At
      least 2 weeks later, the amphetamine was switched to a placebo of identical
      appearance and given in the same environmental context. [11C]Raclopride binding
      to dopamine D(2/3) receptors was assessed after exposure to the first amphetamine
      containing pill, after placebo administration, and during a control (no pill)
      scan. Relative to the control scan, amphetamine administration decreased
      [11C]raclopride binding potential by 22% in the ventral striatum and 11% in the
      putamen. Placebo also decreased [11C]raclopride binding potential in the ventral
      striatum and did so with the same amplitude as amphetamine (23%). These results
      suggest that cues associated with amphetamine increase dopamine transmission,
      providing evidence that this system is involved in reward prediction in humans.

PMID- 17428976
TI  - Accelerated brain gray matter loss in fibromyalgia patients: premature aging of
      the brain?
AB  - Fibromyalgia is an intractable widespread pain disorder that is most frequently
      diagnosed in women. It has traditionally been classified as either a
      musculoskeletal disease or a psychological disorder. Accumulating evidence now
      suggests that fibromyalgia may be associated with CNS dysfunction. In this study,
      we investigate anatomical changes in the brain associated with fibromyalgia.
      Using voxel-based morphometric analysis of magnetic resonance brain images, we
      examined the brains of 10 female fibromyalgia patients and 10 healthy controls.
      We found that fibromyalgia patients had significantly less total gray matter
      volume and showed a 3.3 times greater age-associated decrease in gray matter than
      healthy controls. The longer the individuals had had fibromyalgia, the greater
      the gray matter loss, with each year of fibromyalgia being equivalent to 9.5
      times the loss in normal aging. In addition, fibromyalgia patients demonstrated
      significantly less gray matter density than healthy controls in several brain
      regions, including the cingulate, insular and medial frontal cortices, and
      parahippocampal gyri. The neuroanatomical changes that we see in fibromyalgia
      patients contribute additional evidence of CNS involvement in fibromyalgia. In
      particular, fibromyalgia appears to be associated with an acceleration of age
      related changes in the very substance of the brain. Moreover, the regions in
      which we demonstrate objective changes may be functionally linked to core
      features of the disorder including affective disturbances and chronic widespread
      pain.

PMID- 17428977
TI  - Actin filaments mediate mechanical gating during osmosensory transduction in rat
      supraoptic nucleus neurons.
AB  - Osmosensory transduction is a bidirectional process displayed by neurons involved
      in the control of thirst and antidiuretic hormone release, and is therefore
      crucial for body fluid homeostasis. Although this mechanism is known to involve
      the activation of nonselective cation channels during hypertonicity-evoked
      shrinking, and the inhibition of these channels during hypotonicity-evoked
      swelling, the basis for this regulation is unknown. Here, we investigated this
      process using whole-cell patch-clamp recordings from neurons acutely isolated
      from the supraoptic nucleus of adult rats. The mechanosensitivity index, defined
      as the ratio of conductance change to normalized volume change, was
      quantitatively equivalent whether cell volume was increased or decreased by
      changes in extracellular fluid osmolality, or by changes in pipette pressure.
      Moreover, responses induced by hyperosmotic or hypo-osmotic media could be
      reversed by increasing or decreasing pipette pressure, respectively. The
      mechanosensitivity index was significantly reduced in neurons treated with
      cytochalasin-D, a compound that promotes the depolymerization of actin filaments.
      Conversely, cells treated with jasplakinolide, a compound that promotes actin
      polymerization, showed a significant increase in mechanosensitivity index.
      Finally, the depolarizing and excitatory effects of hypertonic stimuli were
      significantly enhanced by jasplakinolide and reduced by cytochalasin-D. We
      conclude that osmosensory transduction in these neurons is a reversible
      mechanical process that depends on an intact actin cytoskeleton, and the
      sensitivity of the transducer appears to vary in proportion with the density of
      actin filaments.

PMID- 17428978
TI  - Presynaptic FMR1 genotype influences the degree of synaptic connectivity in a
      mosaic mouse model of fragile X syndrome.
AB  - Almost all female and some male fragile X syndrome (FXS) patients are mosaic for
      expression of the FMR1 gene, yet all research in models of FXS has been in
      animals uniformly lacking Fmr1 expression. Therefore, we developed a system
      allowing neuronal genotype to be visualized in vitro in mouse brain slices mosaic
      for Fmr1 expression. Whole-cell recordings from individual pairs of presynaptic
      and postsynaptic neurons in organotypic hippocampal slices were used to probe the
      cell-autonomous effects of Fmr1 genotype in mosaic networks. These recordings
      revealed that wild-type presynaptic neurons formed synaptic connections at a
      greater rate than presynaptic neurons lacking normal Fmr1 function in mosaic
      networks. At the same time, the postsynaptic Fmr1 genotype did not influence the
      probability that a neuron received synaptic connections. Asymmetric presynaptic
      function during development of the brain could result in a decreased
      participation in network function by the portion of neurons lacking FMR1
      expression.

PMID- 17428979
TI  - Determining the neural substrates of goal-directed learning in the human brain.
AB  - Instrumental conditioning is considered to involve at least two distinct learning
      systems: a goal-directed system that learns associations between responses and
      the incentive value of outcomes, and a habit system that learns associations
      between stimuli and responses without any link to the outcome that that response
      engendered. Lesion studies in rodents suggest that these two distinct components
      of instrumental conditioning may be mediated by anatomically distinct neural
      systems. The aim of the present study was to determine the neural substrates of
      the goal-directed component of instrumental learning in humans. Nineteen human
      subjects were scanned with functional magnetic resonance imaging while they
      learned to choose instrumental actions that were associated with the subsequent
      delivery of different food rewards (tomato juice, chocolate milk, and orange
      juice). After training, one of these foods was devalued by feeding the subject to
      satiety on that food. The subjects were then scanned again, while being re
      exposed to the instrumental choice procedure (in extinction). We hypothesized
      that regions of the brain involved in goal-directed learning would show changes
      in their activity as a function of outcome devaluation. Our results indicate that
      neural activity in one brain region in particular, the orbitofrontal cortex,
      showed a strong modulation in its activity during selection of a devalued
      compared with a nondevalued action. These results suggest an important
      contribution of orbitofrontal cortex in guiding goal-directed instrumental
      choices in humans.

PMID- 17428980
TI  - Glutamatergic and purinergic receptor-mediated calcium transients in Bergmann
      glial cells.
AB  - Astrocytes respond to neuronal activity with [Ca2+]i increases after activation
      of specific receptors. Bergmann glial cells (BGs), astrocytes of the cerebellar
      molecular layer (ML), express various receptors that can mobilize internal Ca2+.
      BGs also express Ca2+ permeable AMPA receptors that may be important for
      maintaining the extensive coverage of Purkinje cell (PC) excitatory synapses by
      BG processes. Here, we examined Ca2+ signals in single BGs evoked by synaptic
      activity in cerebellar slices. Short bursts of high-frequency stimulation of the
      ML elicited Ca2+ transients composed of a small-amplitude fast rising phase,
      followed by a larger and slower rising phase. The first phase resulted from Ca2+
      influx through AMPA receptors, whereas the second phase required release of Ca2+
      from internal stores initiated by P2 purinergic receptor activation. We found
      that such Ca2+ responses could be evoked by direct activation of neurons
      releasing ATP onto BGs or after activation of metabotropic glutamate receptor 1
      on these neurons. Moreover, examination of BG and PC responses to various
      synaptic stimulation protocols suggested that ML interneurons are likely the
      cellular source of ATP.

PMID- 17428981
TI  - High-resolution in vivo imaging of the neurovascular unit during spreading
      depression.
AB  - Spreading depression (SD) is a propagating wave of neuronal depolarization and
      ionic shifts, seen in stroke and migraine. In vitro, SD is associated with
      astrocytic [Ca2+] waves, but it is unclear what role they play and whether they
      influence cerebral blood flow, which is altered in SD. Here we show that SD in
      vivo is associated with [Ca2+] waves in astrocytes and neurons and with
      constriction of intracortical arterioles severe enough to result in arrest of
      capillary perfusion. The vasoconstriction is correlated with fast astrocytic
      [Ca2+] waves and is inhibited when they are reduced. [Ca2+] waves appear in
      neurons before astrocytes, and inhibition of astrocytic [Ca2+] waves does not
      depress SD propagation. This suggests that astrocytes do not drive SD propagation
      but are responsible for the hemodynamic failure seen deep in the cortex. Similar
      waves occur in anoxic depolarizations (AD), supporting the notion that SD and AD
      are related processes.

PMID- 17428982
TI  - Anatomical correlates of directional hypokinesia in patients with hemispatial
      neglect.
AB  - Unilateral spatial neglect (neglect) is a syndrome characterized by perceptual
      deficits that prevent patients from attending and responding to the side of space
      and of the body opposite a damaged hemisphere (contralesional side). Neglect also
      involves motor deficits: patients may be slower to initiate a motor response to
      targets appearing in the left hemispace, even when using their unaffected arm
      (directional hypokinesia). Although this impairment is well known, its anatomical
      correlate has not been established. We tested 52 patients with neglect after
      right hemisphere stroke, and conducted an anatomical analysis on 29 of them to
      find the anatomical correlate of directional hypokinesia. We found that patients
      with directional hypokinesia had a lesion involving the ventral lateral putamen,
      the claustrum, and the white matter underneath the frontal lobe. Most
      importantly, none of the patients without directional hypokinesia had a lesion in
      the same region. The localization of neglect's motor deficits to the basal
      ganglia establishes interesting homologies with animal data; it also suggests
      that a relative depletion of dopamine in the nigrostriatal pathway on the same
      side of the lesion may be an important pathophysiological mechanism potentially
      amenable to intervention.

PMID- 17428983
TI  - Apolipoprotein receptor 2 and X11 alpha/beta mediate apolipoprotein E-induced
      endocytosis of amyloid-beta precursor protein and beta-secretase, leading to
      amyloid-beta production.
AB  - The homeostasis of amyloid-beta (Abeta) in the brain is critical to the
      pathogenesis of Alzheimer's disease (AD). Abeta is a fragment of amyloid-beta
      precursor protein (APP) generated in neurons by two proteases, beta- and gamma
      secretases. APP and beta-secretase, both present on cell surface, are endocytosed
      into endosomes to produce Abeta. The molecular mechanism by which neurons trigger
      the production of Abeta is poorly understood. We describe here evidence that the
      binding of lipid-carrying apolipoprotein E (ApoE) to receptor apolipoprotein E
      receptor 2 (ApoER2) triggers the endocytosis of APP, beta-secretase, and ApoER2
      in neuroblastoma cells, leading to the production of Abeta. This mechanism,
      mediated by adaptor protein X11alpha or X11beta (X11alpha/beta), whose PTB
      (phosphotyrosine-binding) domain binds to APP and a newly recognized motif in the
      cytosolic domain of ApoER2. Isomorphic form ApoE4 triggers the production of more
      Abeta than by ApoE2 or ApoE3; thus, it may play a role in the genetic risk of
      ApoE4 for the sporadic AD. The mechanism, which functions independently from
      Reelin-ApoER2 interaction, also provides a link between lipid uptake and Abeta
      production, which may be important for the regulation of neuronal activity.

PMID- 17428984
TI  - Muscarinic control of long-range GABAergic inhibition within the rhinal cortices.
AB  - The perirhinal cortex plays a critical role in memory formation, in part because
      it forms reciprocal connections with the neocortex and entorhinal cortex and is
      thus in a position to integrate and transfer higher-order information to and from
      the hippocampus. However, for reasons that remain unclear, perirhinal transfer of
      neocortical inputs to the entorhinal cortex occurs with a low probability. Using
      patch recordings in vitro and tract-tracing combined with GAD-67
      immunohistochemistry, we show that the perirhinal cortex contains GABAergic
      neurons with long-range projections to superficial entorhinal cells. This finding
      challenges the traditional model of cortical inhibition in which all trans-areal
      inhibition is thought to be disynaptic because the axons of GABAergic
      interneurons are assumed to be confined within the area in which their somata are
      located. Moreover, consistent with recent studies indicating that the formation
      of perirhinal-dependent memories requires activation of muscarinic receptors,
      long-range IPSPs were presynaptically inhibited by M2 receptor activation.
      Overall, these results suggest that long-range feedforward inhibition regulates
      perirhinal transfer of neocortical inputs to the entorhinal cortex, but that
      cholinergic inputs can presynaptically adjust the impact of this control
      mechanism as a function of environmental contingencies.

PMID- 17428985
TI  - Cysteine substitution mutants give structural insight and identify ATP binding
      and activation sites at P2X receptors.
AB  - P2X receptors for extracellular ATP are a distinct family of ligand-gated cation
      channels involved in physiological processes ranging from synaptic transmission
      to muscle contraction. Common ATP binding motifs are absent from P2X receptors,
      and the extent of the agonist binding site is unclear. We used cysteine-scanning
      mutagenesis, radiolabeled 2-azido ATP binding, and methanethiosulfonate (MTS)
      compounds to identify amino acid residues involved in ATP binding and gating of
      the human P2X1 receptor. The pattern of MTSEA [(2-aminoethyl)methanethiosulfonate
      hydrobromide] biotinylation was also used to determine the accessibility of
      substituted cysteine residues and whether this changed on addition of ATP.
      Analysis of cysteine-substituted mutants of the last 44 amino acid residues (S286
      I329) in the extracellular loop before the second transmembrane segment showed
      that N290, F291, R292, and K309 mutants had reduced ATP potency and 2-azido ATP
      binding. MTS reagents produced additional shifts in ATP potency at these
      residues, suggesting that they are directly involved in ATP binding; the effects
      were dependent on the charge of the MTS reagent at K309C; one explanation for
      this is that K309 interacts directly with the negatively charged phosphate of
      ATP. The remainder of the cysteine substitutions had little or no effect on ATP
      potency. However, at the mutants D316C, G321C, A323C, and I328C, MTS reagents did
      not change ATP potency but modified agonist-evoked responses, suggesting that
      this region may contribute to the gating of the channel.

PMID- 17428986
TI  - M1 and M3 muscarinic receptors control physiological processing of cellular prion
      by modulating ADAM17 phosphorylation and activity.
AB  - The cellular prion protein (PrP(c)) undergoes a physiological processing yielding
      the N-terminal fragment referred to as N1, the production of which can be
      constitutive or protein kinase C regulated. We show that activation of endogenous
      muscarinic receptors by carbachol and by the M1-selective agonist AF267B
      increases N1 recovery in an atropine-sensitive manner, in mouse embryonic primary
      neurons. To identify the muscarinic receptor subtype involved, we used human
      embryonic kidney HEK293 (HEK) cells stably overexpressing M1, M2, M3, or M4
      receptor subtype. Carbachol and the selective M1 agonist AF267B dose dependently
      increased N1 release by HEK-M3 and HEK-M1 cells, respectively, whereas carbachol
      did not modify N1 production by HEK-M2 or HEK-M4 cells. We demonstrate that the
      increase of N1 was not attributable to modified trafficking to the membrane of
      either PrP(c) or the disintegrin metalloproteases ADAM10 or ADAM17. Furthermore,
      we establish that carbachol affects the overall phosphorylation of ADAM17 on its
      threonine and tyrosine but not serine residues, whereas levels of phosphorylated
      ADAM9 were not affected. Interestingly, carbachol also increases the hydrolysis
      of the fluorimetric substrate JMV2770, which mimicked the sequence encompassing
      the N1 site cleavage and was shown previously to behave as an ADAM protease
      substrate. Mutations of threonine 735 but not of tyrosine 702 of the ADAM17
      cytoplasmic tail abolishes the carbachol-induced increase of N1, ADAM17
      phosphorylation, and JMV2770-hydrolyzing activity in M1- and M3-expressing HEK293
      cells. Thus, our data provide strong evidence that muscarinic receptor activation
      increases the physiological processing of PrP(c) by upregulating the
      phosphorylation state and activity of ADAM17 protease.

PMID- 17428987
TI  - Looming biases in monkey auditory cortex.
AB  - Looming signals (signals that indicate the rapid approach of objects) are
      behaviorally relevant signals for all animals. Accordingly, studies in primates
      (including humans) reveal attentional biases for detecting and responding to
      looming versus receding signals in both the auditory and visual domains. We
      investigated the neural representation of these dynamic signals in the lateral
      belt auditory cortex of rhesus monkeys. By recording local field potential and
      multiunit spiking activity while the subjects were presented with auditory
      looming and receding signals, we show here that auditory cortical activity was
      biased in magnitude toward looming versus receding stimuli. This directional
      preference was not attributable to the absolute intensity of the sounds nor can
      it be attributed to simple adaptation, because white noise stimuli with identical
      amplitude envelopes did not elicit the same pattern of responses. This
      asymmetrical representation of looming versus receding sounds in the lateral belt
      auditory cortex suggests that it is an important node in the neural network
      correlate of looming perception.

PMID- 17428988
TI  - Extensive turnover of dendritic spines and vascular remodeling in cortical
      tissues recovering from stroke.
AB  - Recovery of function after stroke is thought to be dependent on the
      reorganization of adjacent, surviving areas of the brain. Macroscopic imaging
      studies (functional magnetic resonance imaging, optical imaging) have shown that
      peri-infarct regions adopt new functional roles to compensate for damage caused
      by stroke. To better understand the process by which these regions reorganize, we
      used in vivo two-photon imaging to examine changes in dendritic and vascular
      structure in cortical regions recovering from stroke. In adult control mice,
      dendritic arbors were relatively stable with very low levels of spine turnover
      (<0.5% turnover over 6 h). After stroke, however, the organization of dendritic
      arbors in peri-infarct cortex was fundamentally altered with both apical
      dendrites and blood vessels radiating in parallel from the lesion. On a finer
      scale, peri-infarct dendrites were exceptionally plastic, manifested by a
      dramatic increase in the rate of spine formation that was maximal at 1-2 weeks (5
      8-fold increase), and still evident 6 weeks after stroke. These changes were
      selective given that turnover rates were not significantly altered in ipsilateral
      cortical regions more distant to the lesion (>1.5 mm). These data provide a
      structural framework for understanding functional and behavioral changes that
      accompany brain injury and suggest new targets that could be exploited by future
      therapies to rebuild and rewire neuronal circuits lost to stroke.

PMID- 17428989
TI  - An intersubunit trigger of channel gating in the muscle nicotinic receptor.
AB  - Binding of neurotransmitter triggers gating of synaptic receptor channels, but
      our understanding of the structures that link the binding site to the channel is
      just beginning to develop. Here, we identify an intersubunit triggering element
      required for rapid and efficient gating of muscle nicotinic receptors using a
      structural model of the Torpedo receptor at 4 A resolution, recordings of
      currents through single receptor channels, measurements of inter-residue
      energetic coupling, and functional consequences of disulfide trapping. Mutation
      of the conserved residues, alphaTyr 127, epsilonAsn 39, and deltaAsn 41, located
      at the two subunit interfaces that form the agonist binding sites, markedly
      attenuates acetylcholine-elicited channel gating; mutant cycle analyses based on
      changes in the channel gating equilibrium constant reveal strong energetic
      coupling among these residues. After each residue is substituted with Cys,
      oxidizing conditions that promote disulfide bond formation attenuate gating of
      mutant, but not wild-type receptors. Gating is similarly attenuated when the Cys
      substitutions are confined to either of the binding-site interfaces, but can be
      restored by reducing conditions that promote disulfide bond breakage. Thus, the
      Tyr-Asn pair is an intersubunit trigger of rapid and efficient gating of muscle
      nicotinic receptors.

PMID- 17428990
TI  - Early cross-modal interactions in auditory and visual cortex underlie a sound
      induced visual illusion.
AB  - When a single flash of light is presented interposed between two brief auditory
      stimuli separated by 60-100 ms, subjects typically report perceiving two flashes
      (Shams et al., 2000, 2002). We investigated the timing and localization of the
      cortical processes that underlie this illusory flash effect in 34 subjects by
      means of 64-channel recordings of event-related potentials (ERPs). A difference
      ERP calculated to isolate neural activity associated with the illusory second
      flash revealed an early modulation of visual cortex activity at 30-60 ms after
      the second sound, which was larger in amplitude in subjects who saw the illusory
      flash more frequently. These subjects also showed this early modulation in
      response to other combinations of auditory and visual stimuli, thus pointing to
      consistent individual differences in the neural connectivity that underlies cross
      modal integration. The overall pattern of cortical activity associated with the
      cross-modally induced illusory flash, however, differed markedly from that evoked
      by a real second flash. A trial-by-trial analysis showed that short-latency ERP
      activity localized to auditory cortex and polymodal cortex of the temporal lobe,
      concurrent with gamma bursts in visual cortex, were associated with perception of
      the double-flash illusion. These results provide evidence that perception of the
      illusory second flash is based on a very rapid dynamic interplay between auditory
      and visual cortical areas that is triggered by the second sound.

PMID- 17428991
TI  - Human cortical neurons originate from radial glia and neuron-restricted
      progenitors.
AB  - Understanding the molecular and physiological determinants of cortical neuronal
      progenitor cells is essential for understanding the development of the human
      brain in health and in disease. We used surface marker fucose N-acetyl
      lactosamine (LeX) (also known as CD15) to isolate progenitor cells from the
      cortical ventricular/subventricular zone of human fetal brain at the second
      trimester of gestation and to study their progeny in vitro. LeX+ cells had
      typical bipolar morphology, radial orientation, and antigen profiles,
      characterizing them as a subtype of radial glia (RG) cells. Four complementary
      experimental techniques (clonal analysis, immunofluorescence, transfection
      experiments, and patch-clamp recordings) indicated that this subtype of RG
      generates mainly astrocytes but also a small number of cortical neurons. The
      neurogenic capabilities of RGs were both region and stage dependent. Present
      results provide the first direct evidence that RGs in the human cerebral cortex
      serve as neuronal progenitors. Simultaneously, another progenitor subtype was
      identified as proliferating cells labeled with neuronal (beta-III-tubulin and
      doublecortin) but not RG markers [GFAP, vimentin, and BLBP (brain lipid-binding
      protein)]. Proliferative and antigenic characteristics of these cells suggested
      their neuron-restricted progenitor status. In summary, our in vitro study
      suggests that diverse populations of cortical progenitor cells, including
      multipotent RGs and neuron-restricted progenitors, contribute differentially to
      cortical neurogenesis at the second trimester of gestation in human cerebral
      cortex.

PMID- 17428992
TI  - Selective attention to visual stimuli reduces cochlear sensitivity in
      chinchillas.
AB  - It is generally accepted that during periods of attention to specific stimuli
      there are changes in the neural activity of central auditory structures; however,
      it is controversial whether attention can modulate auditory responses at the
      cochlear level. Several studies performed in animals as well as in humans have
      attempted to find a modulation of cochlear responses during visual attention with
      contradictory results. Here, we have appraised cochlear sensitivity in behaving
      chinchillas by measuring, with a chronically implanted round-window electrode,
      sound-evoked auditory-nerve compound action potentials and cochlear microphonics,
      a measure of outer hair cell function, during selective attention to visual
      stimuli. Chinchillas were trained in a visual discrimination or in an auditory
      frequency discrimination two-choice task. We found a significant decrease of
      cochlear sensitivity during the period of attention to visual stimuli in the
      animals performing the visual discrimination task, but not in those performing
      the auditory task, demonstrating that this physiological effect is related to
      selective attention to visual stimuli rather than to an increment in arousal
      level. Furthermore, the magnitude of the cochlear-sensitivity reductions
      increased in sessions performed with shorter target-light durations (4-0.5 s),
      suggesting that this effect is stronger for higher attentional demands of the
      task. These results demonstrate that afferent auditory activity is modulated by
      selective attention as early as at sensory transduction, possibly through
      activation of olivocochlear efferent fibers.

PMID- 17428993
TI  - Nonsteroidal anti-inflammatory drugs promote axon regeneration via RhoA
      inhibition.
AB  - After a CNS injury in the adult mammals, axonal regeneration is very limited
      because of the reduced intrinsic growth capacity and nonpermissive environment
      for axonal elongation. The growth inhibitions from CNS myelin and astroglial
      chondroitin sulfate proteoglycans partially account for the lack of CNS repair.
      Here, we show that the nonsteroidal antiinflammatory drugs (NSAIDs) ibuprofen and
      indomethacin, the drugs widely used as pain relievers in the clinic, can surmount
      axon growth restrictions from myelin and proteoglycans by potently inhibiting
      their downstream pathway RhoA signal. Similar to Rho and Rock inhibitors C3
      transferase or Y27632 [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)
      cyclohexanecarboxamide], both NSAID drugs stimulate a significant neurite growth
      in the cultured dorsal root ganglion neurons exposed to the inhibitory
      substrates. Systemic administration of ibuprofen to spinal cord-lesioned rodents
      reverses the active RhoA signal around injury area measured via Rho-GTP binding
      assay. Subcutaneous injections of ibuprofen via minipumps to rats with a thoracic
      spinal cord transection or contusion injury result in substantial corticospinal
      and serotonergic axon sprouting in the caudal spinal cord and promote locomotor
      functional recovery, even delaying the treatment 1 week after trauma. In
      contrast, the non-RhoA-inhibiting NSAID naproxen does not have the axon growth
      promoting effects on cultured or lesioned neurons. These studies demonstrate the
      therapeutic potential of RhoA-inhibiting NSAIDs in treating CNS injuries
      characterized by axonal disconnection including spinal cord injury.

PMID- 17428994
TI  - A molecular basis of analgesic tolerance to cannabinoids.
AB  - Clinical usage of cannabinoids in chronic pain states is limited by their central
      side effects and the pharmacodynamic tolerance that sets in after repeated
      dosage. Analgesic tolerance to cannabinoids in vivo could be caused by agonist
      induced downregulation and intracellular trafficking of cannabinoid receptors,
      but little is known about the molecular mechanisms involved. We show here that
      the type 1 cannabinoid receptor (CB1) interacts physically with G-protein
      associated sorting protein 1 (GASP1), a protein that sorts receptors in lysosomal
      compartments destined for degradation. CB1-GASP1 interaction was observed to be
      required for agonist-induced downregulation of CB1 in spinal neurons ex vivo as
      well as in vivo. Importantly, uncoupling CB1 from GASP1 in mice in vivo abrogated
      tolerance toward cannabinoid-induced analgesia. These results suggest that GASP1
      is a key regulator of the fate of CB1 after agonist exposure in the nervous
      system and critically determines analgesic tolerance to cannabinoids.

PMID- 17428995
TI  - Visual phosphene perception modulated by subthreshold crossmodal sensory
      stimulation.
AB  - Crossmodal sensory interactions serve to integrate behaviorally relevant sensory
      stimuli. In this study, we investigated the effect of modulating crossmodal
      interactions between visual and somatosensory stimuli that in isolation do not
      reach perceptual awareness. When a subthreshold somatosensory stimulus was
      delivered within close spatiotemporal congruency to the expected site of
      perception of a phosphene, a subthreshold transcranial magnetic stimulation pulse
      delivered to the occipital cortex evoked a visual percept. The results suggest
      that under subthreshold conditions of visual and somatosensory stimulation,
      crossmodal interactions presented in a spatially and temporally specific manner
      can sum up to become behaviorally significant. These interactions may reflect an
      underlying anatomical connectivity and become further enhanced by attention
      modulation mechanisms.

PMID- 17428996
TI  - Functional responses in the human spinal cord during willed motor actions:
      evidence for side- and rate-dependent activity.
AB  - Although the spinal cord is the output station of the central motor system,
      little is known about the relationships between its functional activity and
      willed movement parameters in humans. We investigated here blood oxygenation
      level-dependent functional magnetic resonance imaging (fMRI) signal changes in
      the cervical spinal cord during a simple finger-to-thumb opposition task in 13
      right-handed volunteers, using a dedicated array of 16 receive-only surface coils
      on a 3 Tesla MRI system. In a first experiment, we found significant fMRI signal
      increases on both sides of the lower cervical spinal cord while subjects
      performed the motor task at a comfortable pace (approximately 0.5 Hz) using
      either hand. Both the spatial extent of movement-related clusters and peak signal
      increases were significantly higher on the side of the cord ipsilateral to the
      moving hand than on the contralateral side. Movement-related activity was
      consistently larger than signal fluctuations during rest. In a second experiment,
      we recorded spinal cord responses while the same motor sequence was performed
      using the dominant hand at two different rates (approximately 0.5 or 1 Hz). The
      intensity but not the spatial extent of the response was larger during higher
      rates, and it was higher on the ipsilateral side of the cord. Notwithstanding the
      limited spatial resolving power of the adopted technique, the present results
      clearly indicate that the finger movement-related fMRI signals recorded from the
      spinal cord have a neural origin and that as a result of recent technological
      advances, fMRI can be used to obtain novel and quantitative physiological
      information on the activity of spinal circuits.

PMID- 17428997
TI  - Distribution of interaural time difference in the barn owl's inferior colliculus
      in the low- and high-frequency ranges.
AB  - Interaural time differences are an important cue for azimuthal sound
      localization. It is still unclear whether the same neuronal mechanisms underlie
      the representation in the brain of interaural time difference in different
      vertebrates and whether these mechanisms are driven by common constraints, such
      as optimal coding. Current sound localization models may be discriminated by
      studying the spectral distribution of response peaks in tuning curves that
      measure the sensitivity to interaural time difference. The sound localization
      system of the barn owl has been studied intensively, but data that would allow
      discrimination between currently discussed models are missing from this animal.
      We have therefore obtained extracellular recordings from the time-sensitive
      subnuclei of the barn owl's inferior colliculus. Response peaks were broadly
      scattered over the physiological range of interaural time differences. A change
      in the representation of the interaural phase differences with frequency was not
      observed. In some neurons, response peaks fell outside the physiological range of
      interaural time differences. For a considerable number of neurons, the peak
      closest to zero interaural time difference was not the behaviorally relevant
      peak. The data are in best accordance with models suggesting that a place code
      underlies the representation of interaural time difference. The data from the
      high-frequency range, but not from the low-frequency range, are consistent with
      predictions of optimal coding. We speculate that the deviation of the
      representation of interaural time difference from optimal-coding models in the
      low-frequency range is attributable to the diminished importance of low
      frequencies for catching prey in this species.

PMID- 17428998
TI  - Biochemical and behavioral evidence for antidepressant-like effects of 5-HT6
      receptor stimulation.
AB  - The primary action of several antidepressant treatments used in the clinic raises
      extracellular concentrations of serotonin (5-HT), which subsequently act on
      multiple 5-HT receptors. The present study examined whether 5-HT6 receptors might
      be involved in the antidepressant-like effects mediated by enhanced
      neurotransmission at 5-HT synapses. A selective 5-HT6 receptor antagonist,
      SB271046, was evaluated for its ability to counteract fluoxetine-induced
      biochemical and behavioral responses in mice. In addition, biochemical and
      behavioral effects of the 5-HT6 receptor agonist, 2-ethyl-5-methoxy-N,N
      dimethyltryptamine (EMDT), were assessed in mice to ascertain whether enhancement
      of 5-HT6 receptor-mediated neurotransmission engenders antidepressant-like
      effects. SB271046 significantly counteracted the stimulatory actions of
      fluoxetine on cortical c-fos mRNA, phospho-Ser845-GluR1, and in the tail
      suspension antidepressant assay, whereas it had no effect on these parameters by
      itself. EMDT increased the phosphorylation states of Thr34-DARPP-32 and Ser845
      GluR1, both in brain slices and in the intact brain, which were effects also seen
      with the antidepressant fluoxetine; as with fluoxetine, these effects were
      demonstrated to be independent of D1 receptor stimulation. Systemic
      administration of EMDT increased c-fos mRNA expression in the striatum and
      cerebral cortex and reduced immobility in the tail suspension test. The
      antidepressant-like effects of EMDT in the tail suspension test were prevented by
      SB271046. Our results indicate that 5-HT6 receptor stimulation may be a mechanism
      initiating some of the biochemical and behavioral outcomes of 5-HT reuptake
      inhibitors, such as fluoxetine. These findings also indicate that selective 5-HT6
      receptor agonists may represent a novel antidepressant drug class.

PMID- 17428999
TI  - Wnt signaling promotes regeneration in the retina of adult mammals.
AB  - Regeneration in the mammalian CNS is severely limited. Unlike in the chick,
      current models hold that retinal neurons are never regenerated. Previously we
      demonstrated that, in the adult mammalian retina, Muller glia dedifferentiate and
      produce retinal cells, including photoreceptors, after acute neurotoxic injury in
      vivo. However, the number of newly generated retinal neurons is very limited.
      Here we demonstrate that Wnt (wingless-type MMTV integration site family)/beta
      catenin signaling promotes proliferation of Muller glia-derived retinal
      progenitors and neural regeneration after damage or during degeneration. Wnt3a
      treatment increases proliferation of dedifferentiated Muller glia >20-fold in the
      photoreceptor-damaged retina. Supplementation with retinoic acid or valproic acid
      induces differentiation of these cells primarily into Crx (cone rod homeobox)
      positive and rhodopsin-positive photoreceptors. Notably, injury induces nuclear
      accumulation of beta-catenin, cyclin D1 upregulation, and Wnt/beta-catenin
      reporter activity. Activation of Wnt signaling by glycogen synthase kinase-3beta
      inhibitors promotes retinal regeneration, and, conversely, inhibition of the
      signaling attenuates regeneration. This Wnt3a-mediated regeneration of retinal
      cells also occurs in rd mice, a model of retinal degeneration. These results
      provide evidence that Wnt/beta-catenin signaling contributes to CNS regeneration
      in the adult mammal.

PMID- 17429000
TI  - White matter axon vulnerability to AMPA/kainate receptor-mediated ischemic injury
      is developmentally regulated.
AB  - Periventricular white matter injury (PWMI) is the leading cause of
      neurodevelopmental morbidity in survivors of premature birth. Cerebral ischemia
      is considered a major etiologic factor in the generation of PWMI. In adult white
      matter (WM), ischemic axonal damage is mediated by AMPA/kainate receptors.
      Mechanisms of ischemic axonal injury during development are not well defined. We
      used a murine brain slice model to characterize mechanisms of ischemic axonal
      injury in developing WM. Acute coronal brain slices were prepared from thy1
      yellow fluorescent protein (YFP) mice at postnatal day 3 (P3), P7, P10, and P21.
      Ischemia was simulated by oxygen-glucose deprivation (OGD). YFP-positive axon
      morphology in the corpus callosum was preserved for at least 15 h under normoxic
      conditions. OGD resulted in delayed degeneration of YFP-positive axons,
      characterized by axonal beading, fragmentation, and loss of YFP. AMPA and
      cyclothiazide damaged WM axons at P7, P10, and P21 but not at P3. The
      AMPA/kainate receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl
      benzo[f]quinoxaline-2,3-dione (NBQX) decreased OGD-induced axonal degeneration
      and oligodendrocyte loss at P10 and P21. At P3 and P7, NBQX protected
      oligodendrocytes but did not prevent axonal degeneration after OGD. The NMDA
      receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten
      5,10-imine maleate] provided no protection at any age. These results indicate
      that developing WM axons are susceptible to ischemic injury. However, mechanisms
      of axonal degeneration are developmentally regulated. At P3 and P7, corresponding
      developmentally to the window of peak vulnerability to PWMI in humans, ischemic
      axonal injury is not mediated by AMPA/kainate receptors. Strategies to protect WM
      during this period may be substantially different from those used at later
      developmental stages.

PMID- 17429001
TI  - Answering the call: the influence of neuroimaging and electrophysiological
      evidence on rehabilitation.
AB  - Functional recovery after brain damage or disease is dependent on the
      neuroplastic capability of the cortex and the nonaffected brain. Following
      cortical injury in the motor and sensory regions, the adjacent spared neural
      tissues and related areas undergo modifications that are required in order to
      drive more normal motor control. Current rehabilitation models seek to stimulate
      functional recovery by capitalizing on the inherent potential of the brain for
      positive reorganization after neurological injury or disease. This article
      discusses how neuroimaging and electrophysiological data can inform clinical
      practice; representative data from the modalities of functional magnetic
      resonance imaging, diffusion tensor imaging, magnetoencephalography,
      electroencephalography, and positron emission tomography are cited. Data from a
      variety of central nervous system disease and damage models are presented to
      illustrate how rehabilitation practices are beginning to be shaped and informed
      by neuroimaging and electrophysiological data.

PMID- 17429002
TI  - Use of imaging to assess normal and adaptive muscle function.
AB  - Physical therapists must be able to determine the activity and passive properties
      of the musculoskeletal system in order to accurately plan and evaluate
      therapeutic measures. Discussed in this article are imaging methods that not only
      allow for the measurement of muscle activity but also allow for the measurement
      of cellular processes and passive mechanical properties noninvasively and in
      vivo. The techniques reviewed are T1- and T2-weighted magnetic resonance (MR)
      imaging, MR spectroscopy, cine-phase-contrast MR imaging, MR elastography, and
      ultrasonography. At present, many of these approaches are expensive and not
      readily available in physical therapy clinics but can be found at medical
      centers. However, there are ways of using these techniques to provide important
      knowledge about muscle function. This article proposes creative ways in which to
      use these techniques as evaluative tools.

PMID- 17429003
TI  - Putting the brain on the map: use of transcranial magnetic stimulation to assess
      and induce cortical plasticity of upper-extremity movement.
AB  - The plasticity of the brain is an increasingly important topic for physical
      therapists interested in childhood development, learning, and repair following
      injury. The study of plasticity directly in the human nervous system presents
      numerous challenges, such as the ability to assess neuronal function in vivo
      because of physical impediments, such as the skull, skin, and dura. Transcranial
      magnetic stimulation (TMS), however, has become a suitable, noninvasive, and
      painless technique that can be applied to detect changes in cortical excitability
      as an indicator of neurological changes. Furthermore, repetitive trains of TMS
      themselves can induce plasticity. This article discusses the use of TMS to
      investigate and manipulate plasticity in the human nervous system.

PMID- 17429004
TI  - Understanding neuroimaging.
AB  - Neuroimaging is an emergent method of investigation for studying the human brain
      in healthy and impaired populations. An increasing number of these investigations
      involve topics important to rehabilitation. Thus, a basic understanding of the
      more commonly used neuroimaging techniques is important for understanding and
      interpreting this growing area of research. Included in this article is a
      description of the signal source, the advantages and limitations of each
      technique, considerations for study design, and how to interpret cortical imaging
      data. Particular emphasis is placed on functional magnetic resonance imaging
      because of its ubiquitous presence in rehabilitation research.

PMID- 17429005
TI  - Antidiabetes and antiobesity effect of cryptotanshinone via activation of AMP
      activated protein kinase.
AB  - Metabolic disorders, including type 2 diabetes and obesity, represent major
      health risks in industrialized countries. AMP-activated protein kinase (AMPK) has
      become the focus of a great deal of attention as a novel therapeutic target for
      the treatment of metabolic syndromes, because AMPK has been demonstrated to
      mediate, at least in part, the effects of a number of physiological and
      pharmacological factors that exert beneficial effects on these disorders. Thus,
      the identification of a compound that activates the AMPK pathway would contribute
      significantly to the treatment and management of such syndromes. In service of
      this goal, we have screened a variety of naturally occurring compounds and have
      identified one compound, cryptotanshinone, as a novel AMPK pathway activator.
      Cryptotanshinone was originally isolated from the dried roots of Salvia
      militorrhiza, an herb that is used extensively in Asian medicine and that is
      known to exert beneficial effects on the circulatory system. For the first time,
      in the present study, we have described the potent antidiabetic and antiobesity
      effects of cryptotanshinone, both in vitro and in vivo. Our findings suggest that
      the activation of the AMPK pathway might contribute to the development of novel
      therapeutic approaches for the treatment of metabolic disorders such as type 2
      diabetes and obesity.

PMID- 17429006
TI  - Iron chelation and regulation of the cell cycle: 2 mechanisms of
      posttranscriptional regulation of the universal cyclin-dependent kinase inhibitor
      p21CIP1/WAF1 by iron depletion.
AB  - Iron (Fe) plays a critical role in proliferation, and Fe deficiency results in
      G(1)/S arrest and apoptosis. However, the precise role of Fe in cell-cycle
      control remains unclear. We observed that Fe depletion increased the mRNA of the
      universal cyclin-dependent kinase inhibitor, p21(CIP1/WAF1), while its protein
      level was not elevated. This observation is unique to the G(1)/S arrest seen
      after Fe deprivation, as increased p21(CIP1/WAF1) mRNA and protein are usually
      found when arrest is induced by other stimuli. In this study, we examined the
      posttranscriptional regulation of p21(CIP1/WAF1) after Fe depletion and
      demonstrated that its down-regulation was due to 2 mechanisms: (1) inhibited
      translocation of p21(CIP1/WAF1) mRNA from the nucleus to cytosolic translational
      machinery; and (2) induction of ubiquitin-independent proteasomal degradation.
      Iron chelation significantly (P < .01) decreased p21(CIP1/WAF1) protein half-life
      from 61 (+/- 4 minutes; n = 3) to 28 (+/- 9 minutes, n = 3). Proteasomal
      inhibitors rescued the chelator-mediated decrease in p21(CIP1/WAF1) protein,
      while lysosomotropic agents were not effective. In Fe-replete cells,
      p21(CIP1/WAF1) was degraded in an ubiquitin-dependent manner, while after Fe
      depletion, ubiquitin-independent proteasomal degradation occurred. These results
      are important for considering the mechanism of Fe depletion-mediated cell-cycle
      arrest and apoptosis and the efficacy of chelators as antitumor agents.

PMID- 17429007
TI  - The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+
      progenitor cells: potential role in angiogenesis and endothelial regeneration.
AB  - Tissue regeneration involves the formation of new blood vessels regulated by
      angiogenic factors. We reported recently that the expression of the angiogenic
      factor CCN1 is up-regulated under various pathophysiologic conditions within the
      cardiovascular system. Because CD34+ progenitor cells participate in
      cardiovascular tissue regeneration, we investigated whether CCN1-detected for the
      first time in human plasma-promotes the recruitment of CD34+ progenitor cells to
      endothelial cells, thereby enhancing endothelial proliferation and
      neovascularization. In this study, we demonstrated that CCN1 and supernatants
      from CCN1-stimulated human CD34+ progenitor cells promoted proliferation of
      endothelial cells and angiogenesis in vitro and in vivo. In addition, CCN1
      induced migration and transendothelial migration of CD34+ cells and the release
      of multiple growth factors, chemokines, and matrix metalloproteinase-9 (MMP-9)
      from these cells. Moreover, the CCN1-specific integrins alpha(M)beta(2) and
      alpha(V)beta(3) are expressed on CD34+ cells and CCN1 stimulated integrin
      dependent signaling. Furthermore, integrin antagonists (RGD-peptides) suppressed
      both binding of CCN1 to CD34+ cells and CCN1-induced adhesion of CD34+ cells to
      endothelial cells. These data suggest that CCN1 promotes integrin-dependent
      recruitment of CD34+ progenitor cells to endothelial cells, which may contribute
      to paracrine effects on angiogenesis and tissue regeneration.

PMID- 17429008
TI  - Hydroxyurea therapy lowers transcranial Doppler flow velocities in children with
      sickle cell anemia.
AB  - Hydroxyurea has hematologic and clinical efficacy in sickle cell anemia (SCA),
      but its effects on transcranial Doppler (TCD) flow velocities remain undefined.
      Fifty-nine children initiating hydroxyurea therapy for clinical severity had
      pretreatment baseline TCD measurements; 37 with increased flow velocities (> or =
      140 cm/s) were then enrolled in an institutional review board (IRB)-approved
      prospective phase 2 trial with TCD velocities measured at maximum tolerated dose
      (MTD) and one year later. At hydroxyurea MTD (mean +/- 1 SD = 27.9 +/- 2.7 mg/kg
      per day), significant decreases were observed in the right middle cerebral artery
      (MCA) (166 +/- 27 cm/s to 135 +/- 27 cm/s, P < .001) and left (MCA) (168 +/- 26
      cm/s to 142 +/- 27 cm/s, P < .001) velocities. The magnitude of TCD velocity
      decline was significantly correlated with the maximal baseline TCD value. At
      hydroxyurea MTD, 14 of 15 children with conditional baseline TCD values improved,
      while 5 of 6 with abnormal TCD velocities whose families refused transfusions
      became less than 200 cm/s. TCD changes were sustained at follow-up. These
      prospective data indicate that hydroxyurea can significantly decrease elevated
      TCD flow velocities, often into the normal range. A multicenter trial is
      warranted to determine the efficacy of hydroxyurea for the management of
      increased TCD values, and ultimately for primary stroke prevention in children
      with SCA.

PMID- 17429009
TI  - A screening and intervention program aimed to reduce mortality and serious
      morbidity associated with severe neonatal alloimmune thrombocytopenia.
AB  - The study's objective was to identify HPA 1a-negative women and to offer them an
      intervention program aimed to reduce morbidity and mortality of neonatal
      alloimmune thrombocytopenia (NAIT). HPA 1 typing was performed in 100 448
      pregnant women. The HPA 1a-negative women were screened for anti-HPA 1a. In
      immunized women, delivery was performed by Cesarean section 2 to 4 weeks prior to
      term, with platelets from HPA 1a-negative donors reserved for immediate
      transfusion if petechiae were present and/or if platelet count was less than 35 x
      10(9)/L. Of the women screened, 2.1% were HPA 1a negative, and anti-HPA 1a was
      detected in 10.6% of these. One hundred seventy pregnancies were managed
      according to the intervention program, resulting in 161 HPA 1a-positive children.
      Of these, 55 had severe thrombocytopenia (< 50 x 10(9)/L), including 2 with
      intracranial hemorrhage (ICH). One woman with a twin pregnancy missed the follow
      up and had one stillborn and one severely thrombocytopenic live child. In 15
      previous prospective studies (136 814 women) there were 51 cases of severe NAIT
      (3 intrauterine deaths and 7 with ICH). Acknowledging the limitation of comparing
      with historic controls, implementation of our screening and intervention program
      seemed to reduce the number of cases of severe NAIT-related complications from 10
      of 51 to 3 of 57.

PMID- 17429010
TI  - Effect of recombinant human follicle-stimulating hormone and luteinizing hormone
      on in vitro maturation of porcine oocytes evaluated by the subsequent in vitro
      development of embryos obtained by in vitro fertilization, intracytoplasmic sperm
      injection, or parthenogenetic activation.
AB  - The aim of this work was to study the effect of recombinant human (rh) FSH and LH
      on in vitro maturation of pig oocytes compared with a conventional hormonal
      supplement based on equine (PMSG) and human chorionic gonadotropins (hCG), as
      evaluated by the developmental ability of 3 types of pig embryos obtained by in
      vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), or artificial
      activation (ATA). In Exp. 1, one cumulus-oocyte complex group (A group) was
      supplemented with rh-FSH and rh-LH (0.1 IU/mL each), and the other group (B
      group) was supplemented with PMSG and hCG (10 IU/mL each). No differences in
      nuclear maturation between the A and B groups were observed (68.5 vs. 71.4%,
      respectively). No differences were detected between hormonal treatments in the
      rates of cleavage or blastocyst formation of ATA, IVF, and ICSI embryos. Total
      cell number of the embryos was not significantly different in any experimental
      group (A: 31.1, 28.5, and 19.8 vs. B: 25.2, 25.5, and 20.6 for ATA, IVF, and ICSI
      embryos, respectively). In Exp. 2, the effects of different concentrations of rh
      FSH and rh-LH (0.5, 0.1, or 0.05 IU/mL) in maturation medium on nuclear
      maturation and in vitro development of embryos obtained by IVF were studied. No
      effect of different hormonal concentrations on blastocyst formation rates was
      observed (8.5, 13.0, and 5.7%, respectively). Blastocyst cell number was not
      different in any experimental group. In conclusion, the results obtained here
      permit us to substitute PMSG and hCG with rh-FSH and rh-LH and to produce pig
      embryos obtained by IVF, ICSI, or ATA.

PMID- 17429012
TI  - Activated innate immune system in irritable bowel syndrome?

PMID- 17429013
TI  - Differential modulation of gonadotropin secretion by selective estrogen receptor
      1 and estrogen receptor 2 agonists in ovariectomized ewes.
AB  - The objectives of this study were to determine whether activation of estrogen
      receptor 1 (ESR1; also known as ERalpha), or estrogen receptor 2 (ESR2; also
      known as ERbeta), or both are required to: 1) acutely inhibit secretion of LH, 2)
      induce the preovulatory-like surge of LH, and 3) inhibit secretion of FSH in
      ovariectomized (OVX) ewes. OVX ewes (n = 6) were administered intramuscularly 25
      micrograms estradiol (E2), 12 mg propylpyrazoletriol (PPT; a subtype-selective
      ESR1 agonist), 21 mg diaprylpropionitrile (DPN; a subtype-selective ESR2
      agonist), or PPT + DPN. Like E2, administration of PPT, DPN, or combination of
      the two rapidly decreased (P < 0.05) secretion of LH. Each agonist induced a
      gradual, prolonged rise in secretion of LH after the initial inhibition, but
      neither agonist alone nor the combined agonists was able to induce a "normal"
      preovulatory-like surge of LH similar to that induced by E2. Compared with E2
      treated ewes, the beginning of the increase in secretion of LH occurred earlier
      (P < 0.01) in DPN-treated ewes, later (P < 0.05) in PPT-treated ewes, and at a
      similar interval in ewes receiving the combined agonist treatment. Like E2, PPT
      decreased (P < 0.05) secretion of FSH, but the duration of suppression was much
      longer in PPT-treated ewes. DPN did not alter secretion of FSH in this study.
      Modulation of the number of GnRH receptors by PPT and DPN was examined in primary
      cultures of ovine pituitary cells. In our hands, both PPT and DPN increased the
      number of GnRH receptors, but the dose of DPN required to stimulate synthesis of
      GnRH receptors was 10 times higher than that of PPT. We conclude that in OVX
      ewes: 1) ESR1 and ESR2 mediate the negative feedback of E2 on secretion of LH at
      the level of the pituitary gland, 2) ESR1 and ESR2 do not synergize or antagonize
      the effects of each other; however, they do interact to synchronize the beginning
      of the stimulatory effect of E2 on secretion of LH, 3) ESR1 and ESR2 may mediate
      at least partially the positive feedback of E2 on LH secretion by increasing the
      number of GnRH receptors, and 4) only ESR1 appears to be involved in the negative
      feedback of E2 on secretion of FSH.

PMID- 17429014
TI  - Depletion of ovarian follicles with age in chimpanzees: similarities to humans.
AB  - We retrieved ovarian sections taken from necropsies of 19 captive chimpanzees
      (Pan troglodytes) aged 0-47 yr, counted the number of primordial follicles in
      each, and compared the rate of decline in numbers to declines previously
      documented in humans. The follicular depletion rate in this sample was
      indistinguishable from that shown across the same ages in classic human data
      sets. This result supports earlier suggestions that ovarian senescence occurs at
      the same ages in chimpanzees and humans, implying that the influence of declining
      ovarian function on other physiologic systems may be distinctively buffered in
      humans.

PMID- 17429016
TI  - Differential effects of various estradiol-17beta treatments on follicle
      stimulating hormone peaks, luteinizing hormone pulses, basal gonadotropin
      concentrations, and antral follicle and luteal development in cyclic ewes.
AB  - In a previous study, 10-day estradiol implant treatment truncated the FSH peaks
      that precede follicular waves in sheep, but subsequent ovine FSH (oFSH) injection
      reinitiated wave emergence. The present study's objectives were to examine the
      effects of a 20-day estradiol and progesterone treatment on FSH peaks, follicle
      waves, and responsiveness to oFSH injection. Also, different estradiol doses were
      given to see whether a model that differentially suppressed FSH peaks, LH pulses,
      or basal gonadotropin secretion could be produced in order to study effects of
      these changes on follicular dynamics. Mean estradiol concentrations were 11.8 +/-
      0.4 pg/ml, FSH peaks were truncated, wave emergence was halted, and the number of
      small follicles (2-3 mm in diameter) was reduced (P < 0.05) in cyclic ewes given
      estradiol and progesterone implants (experiment 1). On Day 15 of treatment, oFSH
      injection failed to induce wave emergence. With three different estradiol implant
      sizes (experiment 2), estradiol concentrations were 5.2, 19.0, 27.5, and 34.8 (+/
      4.6) pg/ml in control and treated ewes, respectively. All estradiol treatments
      truncated FSH peaks, except those that created the highest estradiol
      concentrations. Experiment 2-treated ewes had significantly reduced mean and
      basal FSH concentrations and LH pulse amplitude and frequency. We concluded that
      20-day estradiol treatment truncated FSH peaks, blocking wave emergence, and
      reduced the small-follicle pool, rendering the ovary unresponsive to oFSH
      injection in terms of wave emergence. Varying the steroid treatment created
      differential FSH peak regulation compared with other gonadotropin secretory
      parameters. This provides a useful model for future studies of the endocrine
      regulation of ovine antral follicular dynamics.

PMID- 17429015
TI  - The role of aquaporin 3 in the movement of water and cryoprotectants in mouse
      morulae.
AB  - The permeability to water and cryoprotectants of the plasma membrane is crucial
      to the successful cryopreservation of embryos. Previously, we have shown in mouse
      morulae that water and glycerol move across the plasma membrane by facilitated
      diffusion, and we have suggested that aquaporin 3 plays an important role in
      their movement. In the present study, we clarify the contribution of aquaporin 3
      to the movement of water and various cryoprotectants in mouse morulae by
      measuring the Arrhenius activation energies for permeability to cryoprotectants
      and water, through artificial expression of aquaporin 3 using Aqp3 cRNA in mouse
      oocytes, and by suppressing the expression of aquaporin 3 in morulae by injecting
      double-stranded RNA of Aqp3 at the one-cell zygote stage. The results show that
      aquaporin 3 plays an important role in the facilitated diffusion of water,
      glycerol, and ethylene glycol, but not of acetamide and dimethylsulfoxide. On the
      other hand, in a propylene glycol solution, aquaporin 3 in morulae transported
      neither propylene glycol nor water by facilitated diffusion, probably because of
      strong water-solute interactions. These results provide important information for
      understanding the permeability of the plasma membrane of the mouse embryo.

PMID- 17429017
TI  - Milk caseins decrease the binding of the major bovine seminal plasma proteins to
      sperm and prevent lipid loss from the sperm membrane during sperm storage.
AB  - Milk is used as a medium for sperm preservation. Caseins, the major proteins of
      milk, appear to be responsible for the protective effect of milk on sperm.
      Recently, we have shown that egg yolk, which is also widely used to preserve
      semen, protects sperm functions by preventing the binding to sperm of the major
      proteins of bull seminal plasma (BSP proteins), thereby preventing BSP protein
      mediated stimulation of lipid loss from the sperm membrane. In the present study,
      we investigated whether milk caseins protect sperm in the same manner as egg
      yolk. Bovine ejaculates were diluted with skimmed milk permeate (skimmed milk
      devoid of caseins) or permeate that was supplemented with caseins and stored at 4
      degrees C for 4 h. In the semen diluted with permeate, sperm viability and
      motility decreased in a time-dependent manner. However, in semen diluted with
      milk or permeate supplemented with caseins, sperm functions were maintained. In
      addition, lower amounts of the BSP proteins were associated with sperm in semen
      diluted with milk or permeate supplemented with caseins, as compared to semen
      diluted with permeate. No milk proteins were detected in the sperm protein
      extracts. Furthermore, sperm diluted with milk or permeate supplemented with
      caseins showed 3-fold lower losses of cholesterol and choline phospholipids than
      sperm diluted with permeate during storage. Thus, milk caseins decreased the
      binding of BSP proteins to sperm and reduced sperm lipid loss, while maintaining
      sperm motility and viability during storage. These results support our view that
      milk caseins prevent the detrimental effects of BSP proteins on the sperm
      membrane during sperm preservation.

PMID- 17429018
TI  - Changes in lipids containing long- and very long-chain polyunsaturated fatty
      acids in cryptorchid rat testes.
AB  - The aim of the present study was to examine the effects of experimental
      cryptorchidism on rat testicular phospholipids and neutral lipids that contain
      long-chain (C(18)-C(22)) and very long-chain (VLC) (C(24)-C(32)) polyunsaturated
      fatty acids (PUFA). The weight of the cryptorchid testis was nearly half that of
      the contralateral control at postsurgical Days 7-10 owing to the depletion of
      germ cells. Concomitantly, the amounts of major glycerophospholipids (GPL) and
      sphingomyelin (SM) per testis decreased. Both these lipids lost their
      characteristic long-chain and very long-chain PUFA, notably 22:5n-6 and 28:4n-6,
      respectively, which suggests that these species are linked to the membranes of
      germ cells. In contrast, the amounts and concentrations of triglycerides (TG;
      triacylglycerols and 1-O-alkyl-2,3-diacylglycerols) and cholesterol esters (CE)
      increased several fold in the surviving cells (mainly Sertoli cells) in the
      cryptorchid testis. All these neutral lipids, but especially CE, accumulated
      large amounts of the major PUFA of the testis, 22:5n-6, as well as pentaenes with
      longer carbon chains (i.e., 24:5n-6 in TG and 28:5n-6 in CE). This accretion
      suggests that neutral lipids may store preformed PUFA coming from dying germ cell
      GPL and also VLCPUFA no longer needed as a source of PUFA destined to assemble
      new germ cell GPL. The lipid adjustments observed in cryptorchidism suggest a
      possible role for Sertoli cell CE in the turnover and conservation of PUFA within
      seminiferous tubules.

PMID- 17429019
TI  - Typologies of abuse among Afro-Trinidadian women.
AB  - This study examines typologies of abusive behaviors among Afro-Trinidadian women.
      A total of 17 women participated in a 2-hour, face-to-face interview. The
      findings suggest that women experience multiple types of abuse including
      physical, sexual, and emotional abuse and controlling behaviors. This article
      discusses the implications of the findings for interventions with abused women.

PMID- 17429020
TI  - Typologies of adolescent dating violence: identifying typologies of adolescent
      dating violence perpetration.
AB  - Acts scales, the most common way of measuring partner violence, have been
      criticized for being too simplistic to capture the complexities of partner
      violence. An alternative measurement approach is to use typologies that consider
      various aspects of context. In this study, the authors identified typologies of
      dating violence perpetration by adolescents. They conducted in-depth interviews
      with 116 girls and boys previously identified by an acts scale as perpetrators of
      dating violence. They provided narrative descriptions of their dating violence
      acts. For boys and girls, many acts considered violent by the acts scale were
      subsequently recanted or described as nonviolent. From the narratives, they
      identified four types of female perpetration that were distinguished by motives,
      precipitating events, and the abuse history of the partners. One type of
      perpetration accounted for most acts by boys. The findings are discussed relative
      to dating violence measurement, prevention and treatment, and development of
      theory.

PMID- 17429021
TI  - Latent profiles among sexual assault survivors: understanding survivors and their
      assault experiences.
AB  - Little guidance exists about how to tailor empowerment and resistance sexual
      assault programming to be responsive to varying groups of women. Using an
      investigation of 415 college women who completed a self-administered survey about
      a range of sexually aggressive experiences by a known male assailant, this
      investigation tested for distinct multivariate profiles of contextual factors
      among sexually assaulted women to discern how these factors may differentially
      combine to influence women's vulnerability to sexual assault. We applied latent
      profile analysis (LPA) to determine meaningful subgroups of women based on
      interrelationships among factors that contextualize women's vulnerability to
      sexual assault, including prior victimization, alcohol consumption, relationship
      expectancies of the assailant, and assertive precautionary habits. LPA
      established four significantly distinct multivariate profiles of substantively
      different groups of women. Group difference tests reinforced the findings and
      aided in group profile interpretations. Implications for the development of
      tailored resistance and empowerment programs are discussed.

PMID- 17429022
TI  - Latent profiles among sexual assault survivors: implications for defensive coping
      and resistance.
AB  - Rape resistance trainings need to prepare women to recognize and resist sexual
      assault across a range of experiences and contexts. To help address this need,
      this research used an investigation of 415 college women who completed a survey
      about their situational responding to an experience of acquaintance sexual
      assault. A previously established person-centered analysis model of four distinct
      risk and protective factor profiles was used to investigate the variability in
      women's responding. The profiling factors included women's prior victimization,
      alcohol consumption, relationship expectancies of the assailant, and assertive
      precautionary habits. Multivariate ANOVA was used to test for differences among
      the four profile groups on their cognitive, emotional, and behavioral responding.
      Results showed that the profile groups significantly differed in their assault
      responses. The findings highlight the utility of holistic, multivariate analyses
      for understanding women's sexual assault responses and help inform tailored
      resistance and empowerment trainings.

PMID- 17429023
TI  - Perceptions of victims and perpetrators in a depicted child sexual abuse case:
      gender and age factors.
AB  - This study investigated the roles of respondent, perpetrator, and victim gender
      on attributions toward a 10- or 15-year-old victim and an adult perpetrator in a
      hypothetical sexual abuse case. It was predicted (a) that female respondents
      would be more provictim and antiperpetrator than men, (b) that 10-year-old
      victims would be deemed more credible than 15-year-olds, and (c) that men would
      deem a 15-year-old male victim more culpable when child sexual abuse is
      perpetrated by a female abuser. Three hundred thirty-seven respondents read a 350
      word sexual abuse depiction in which victim age, victim gender, and perpetrator
      gender were varied between respondents. Respondents then completed a 14-item
      attribution scale, relating to victim blame, perpetrator blame, assault severity,
      and victim credibility. A series of ANOVAs revealed support for all predictions.
      Results are discussed in relation to gender role attitudes. Suggestions for
      future work also considered.

PMID- 17429024
TI  - Associations of dating violence victimization with lifetime participation, co
      occurrence, and early initiation of risk behaviors among U.S. high school
      students.
AB  - This study examined the association of victimization in a physically violent
      dating relationship with risk behaviors, age of risk behavior initiation, and co
      occurrence of risk behaviors among students in grades 9 through 12 in the United
      States. Data were from the 2003 national Youth Risk Behavior Survey (YRBS).
      Nearly 9% of students reported experiencing dating violence victimization. Dating
      violence victimization was associated with alcohol use, marijuana use, and having
      ever had sexual intercourse among female students and having ever had sexual
      intercourse among male students. Dating violence victimization also was
      associated with early initiation of alcohol use among female students. The odds
      of dating violence victimization increased as the number of risk behaviors
      increased and as the number of lifetime sexual partners increased. These risk
      behavior patterns should serve as warning signs of elevated risk for dating
      violence victimization and may be helpful in identifying adolescents who could
      benefit from targeted, preventive interventions.

PMID- 17429025
TI  - Intimate partner violence during pregnancy and mothers' child abuse potential.
AB  - This research examines whether women who have experienced intimate partner
      violence (IPV) during pregnancy have a higher child abuse potential than women
      who have not experienced IPV. Data were analyzed from a longitudinal
      investigation of IPV during pregnancy. This study recruited 88 pregnant women
      during prenatal care and followed them for 1(1/2) years. IPV was assessed using
      the Conflict Tactics Scale 2 (CTS2). The woman's potential for child abuse was
      assessed using the Child Abuse Potential Inventory (CAPI). There was a
      significant positive association between IPV and child abuse potential scores (p
      = .003), even after controlling for sociodemographics. The odds of having a high
      level of child abuse potential were 3 times greater for women who were victims of
      IPV compared to nonvictims. Higher child abuse potential scores of the victimized
      women resulted mainly from the Distress and Problems with Others CAPI scales.

PMID- 17429026
TI  - My Sassy Girl: a qualitative study of women's aggression in dating relationships
      in Beijing.
AB  - The Korean film My Sassy Girl was very popular among young people in urban China
      in 2001. After the release of the movie, the new image of the "sassy girl"
      emerged in different media. This study uses the media image of the sassy girl as
      a stimulus material in interviews and focus groups to explore how young men and
      women make sense of women's aggression in dating relationships. This qualitative
      study is mainly based on two focus groups and in-depth interviews with 20
      informants (13 female and 7 male). The study sheds light on how the competing and
      multilayered discourses in contemporary China regarding gender, love, and sex
      have left some space for young adults to justify women's aggression in dating
      relationships. We see how young adults in Beijing situate themselves within this
      set of social cultural discourses and make use of them to "do" their gender
      through their aggressive behavior and interactions with each other. New images of
      men and women are thereby created.

PMID- 17429027
TI  - Correlates of partner violence for incarcerated women and men.
AB  - This study examines partner violence within an incarcerated sample of women and
      men. Specifically, it focused on the relationship between explicit and implicit
      attitudes to the perpetration and victimization of violence. Findings revealed
      that violence was bidirectional, with males and females equally likely to report
      being the perpetrator or victim of violence. The attitudes and beliefs associated
      with violence were similar regardless of gender, type of violence (physical or
      psychological), or whether individuals were the victim or perpetrator of
      violence. Hostility to women was the most significant factor associated with
      perpetrating and condoning partner violence. Hostility to women in combination
      with implicit beliefs condoning violence were the strongest predictors for
      suffering physical violence. Victims' self-reported communication problems
      uniquely predicted their suffering of psychological violence. The explanation for
      and consequences of these results are discussed.

PMID- 17429028
TI  - Antioxidant vitamins induce angiogenesis in the normal pig kidney.
AB  - The effects of chronic supplementation with antioxidant vitamins on angiogenesis
      are controversial. The aim of the present study was to evaluate in kidneys of
      normal pigs the effect of chronic supplementation with vitamins E and C, at doses
      that are effective in reducing oxidative stress and attenuating angiogenesis
      under pathological conditions. Domestic pigs were randomized to receive a 12-wk
      normal diet without (n = 6) or with antioxidant vitamins supplementation (1g/day
      vitamin C, 100 IU.kg(-1).day(-1) vitamin E; n = 6). Electron beam computed
      tomography (CT) was used to evaluate renal cortical vascular function in vivo,
      and micro-CT was to assess the spatial density and average diameter of cortical
      microvessels (diameter <500 microm) ex vivo. Oxidative stress and expressions of
      vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)
      1alpha were evaluated in renal tissue. The effects of increasing concentrations
      of the same vitamins on redox status and angiogenesis were also evaluated in
      human umbilical vascular endothelial cells (HUVEC). Compared with normal pigs,
      the density of cortical transmural microvessels was significantly greater in
      vitamin-supplemented pigs (149.0 +/- 11.7 vs. 333.8 +/- 48.1 vessel/cm(2), P <
      0.05), whereas the cortical perfusion response to ACh was impaired. This was
      accompanied by a significant increase in tissue oxidative stress and levels of
      VEGF and HIF-1alpha. A low dose of antioxidant decreased, whereas a high dose
      increased, HUVEC oxidative stress and angiogenesis, which was partly mediated by
      hydrogen peroxide. Antioxidant vitamin supplementation can increase tissue
      oxidative redox and microvascular proliferation in the normal kidney, probably
      due to a biphasic effect that depends on basal redox balance.

PMID- 17429029
TI  - Why is D-serine nephrotoxic and alpha-aminoisobutyric acid protective?
AB  - D-Serine selectively causes necrosis of S(3) segments of proximal tubules in
      rats. This leads to aminoaciduria and glucosuria. Coinjection of the
      nonmetabolizable amino acid alpha-aminoisobutyric acid (AIB) prevents the
      tubulopathy. D-serine is selectively reabsorbed in S(3), thereby gaining access
      to peroxisomal D-amino acid oxidase (D-AAO). D-AAO-mediated metabolism produces
      reactive oxygen species. We determined the fractional excretion of amino acids
      and glucose in rats after intraperitoneal injection of d-serine alone or together
      with reduced glutathione (GSH) or AIB. Both compounds prevented the
      hyperaminoaciduria. We measured GSH concentrations in renal tissue before
      (control) and after D-serine injection and found that GSH levels decreased to
      approximately 30% of control. This decrease was prevented when equimolar GSH was
      coinjected with D-serine. To find out why AIB protected the tubule from D-serine
      toxicity, we microinfused D-[(14)C]serine or [(14)C]AIB (0.36 mmol/l) together
      with [(3)H]inulin in late proximal tubules in vivo and measured the radioactivity
      in the final urine. Fractional reabsorption of D-[(14)C]serine and [(14)C]AIB
      amounted to 55 and 70%, respectively, and 80 mmol/l of AIB or D-serine mutually
      prevented reabsorption to a great extent. D-AAO activity measured in vitro (using
      D-serine as substrate) was not influenced by a 10-fold higher AIB concentration.
      We conclude from these results that 1) D-AAO-mediated d-serine metabolism lowers
      renal GSH concentrations and thereby provokes tubular damage because reduction of
      reactive oxygen species by GSH is diminished and 2) AIB prevents d-serine-induced
      tubulopathy by inhibition of D-serine uptake in S(3) segments rather than by
      interfering with intracellular D-AAO-mediated D-serine metabolism.

PMID- 17429030
TI  - Ontogeny of NHE8 in the rat proximal tubule.
AB  - Proximal tubule bicarbonate reabsorption is primarily mediated via the Na(+)/H(+)
      exchanger, identified as NHE3 in adults. Previous studies have demonstrated a
      maturational increase in rat proximal tubule NHE3 expression, with a paucity of
      NHE3 expression in neonates, despite significant Na(+)-dependent proton
      secretion. Recently, a novel Na(+)/H(+) antiporter (NHE8) was identified and
      found to be expressed on the apical membrane of the proximal tubule. To determine
      whether NHE8 may be the antiporter responsible for proton secretion in neonates,
      the present study characterized the developmental expression of NHE8 in rat
      proximal tubules. RNA blots and real-time RT-PCR demonstrated no developmental
      difference in the mRNA of renal NHE8. Immunoblots, however, demonstrated peak
      protein abundance of NHE8 in brush border membrane vesicles of 7- and 14-day-old
      compared with adult rats. In contrast, the level of NHE8 expression in total
      cortical membrane protein was higher in adults than in neonates.
      Immunohistochemistry confirmed the presence of NHE8 on the apical membrane of the
      proximal tubules of neonatal and adult rats. These data demonstrate that NHE8
      does undergo maturational changes on the apical membrane of the rat proximal
      tubule and may account for the Na(+)-dependent proton flux in neonatal proximal
      tubules.

PMID- 17429031
TI  - Cl- -dependent upregulation of human organic anion transporters: different
      effects on transport kinetics between hOAT1 and hOAT3.
AB  - Chloride ion has a stimulatory effect on the transport of organic anions across
      renal basolateral membranes. However, the exact mechanisms at molecular levels
      have been unclear as of yet. Human organic anion transporters hOAT1 and hOAT3
      play important roles in renal basolateral membranes. In this study, the effects
      of Cl(-) on the activities of these transporters were evaluated by using HEK293
      cells stably expressing hOAT1 or hOAT3 (HEK-hOAT1 or HEK-hOAT3). The uptake of p
      [(14)C]aminohippurate by HEK-hOAT1 and [(3)H]estrone sulfate by HEK-hOAT3 was
      greater in the presence of Cl(-) than in the presence of SO(4)(2-) or gluconate.
      Additionally, the uptake of various compounds by HEK-hOAT1 and HEK-hOAT3 was
      significantly higher in the Cl(-)-containing medium than the gluconate-containing
      medium, suggesting that the influences of Cl(-) are not dependent on substrate
      and that Cl(-) directly stimulates the functions of hOAT1 and hOAT3. The
      substitution of gluconate with Cl(-) did not change the K(m) value for the uptake
      of p-[(14)C]aminohippurate by HEK-hOAT1 but caused an approximately threefold
      increase in the maximal uptake rate (V(max)) value. On the other hand,
      replacement of gluconate with Cl(-) decreased the K(m) value for the uptake of
      [(3)H]estrone sulfate and cefotiam by HEK-hOAT3 to about one-third, while it did
      not change the V(max) value. In summary, Cl(-) upregulates the activities of both
      hOAT1 and hOAT3, but its effects on transport kinetics differ between these
      transporters. It was suggested that Cl(-) participates in the trans-location
      process for hOAT1, and the substrate recognition process for hOAT3.

PMID- 17429032
TI  - Profiling of the renal kinome: a novel tool to identify protein kinases involved
      in angiotensin II-dependent hypertensive renal damage.
AB  - Regulation of protein kinase activities is crucial in both physiology and
      disease, but analysis is hampered by the multitude and complexity of kinase
      networks. We used novel peptide array chips containing 1,152 known kinase
      substrate sequences to profile different kinase activities in renal lysates from
      homozygous Ren2 rats, a model characterized by hypertension and angiotensin II
      (ANG II)-mediated renal fibrosis, compared with Sprague-Dawley (SD) control rats
      and Ren2 rats treated with an angiotensin-converting enzyme inhibitor (ACEi).
      Five-wk-old homozygous Ren2 rats were left untreated or treated with the ACEi
      ramipril (1 mg.kg(-1).day(-1)) for 4 wk; age-matched SD rats served as controls
      (n = 5 each). Peptide array chips were incubated with renal cortical lysates in
      the presence of radioactively labeled ATP. Radioactivity incorporated into the
      substrate motifs was measured to quantify kinase activity. A number of kinases
      with modulated activities, which might contribute to renal damage, were validated
      by Western blotting, immunoprecipitation, and immunohistochemistry. Relevant
      kinases identified by the peptide array and confirmed using conventional
      techniques included p38 MAP kinase and PDGF receptor-beta, which were increased
      in Ren2 and reversed by ACEi. Furthermore, insulin receptor signaling was reduced
      in Ren2 compared with control rats, and G protein-coupled receptor kinase (GRK)
      activity decreased in Ren2 + ACEi compared with untreated Ren2 rats. Array-based
      profiling of tissue kinase activities in ANG II-mediated renal damage provides a
      powerful tool for identification of relevant kinase pathways in vivo and may lead
      to novel strategies for therapy.

PMID- 17429033
TI  - Distant organ injury following acute kidney injury.

PMID- 17429034
TI  - New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of
      aldosterone.
AB  - Cyclosporine A (CsA), a calcineurin inhibitor, has improved allograft survival in
      solid organ transplantation and has been increasingly applied in the management
      of autoimmune diseases. While marked progress has been made in patient and
      allograft survival rates, clinical use of CsA is often limited by its nephrotoxic
      effect, which can be presented as two distinct and well-characterized forms:
      acute and chronic nephrotoxicity. The acute form is characterized by renal
      vasoconstriction, induced by an imbalance of vasoactive substances release, which
      leads to renal dysfunction. This form is reversible. The chronic toxicity, in
      contrast, is characterized by the vasoconstriction plus the development of
      structural damage that includes arteriolopathy and tubulointerstitial fibrosis
      that are often not reversible. The exact mechanisms of these deleterious effects
      are not fully understood, but major advances have occurred over the last few
      years. Here we review the current literature regarding the pathogenesis and
      strategies that have been used to ameliorate renal injury in chronic CsA
      nephrotoxicity. Recent observations suggest that aldosterone plays a central role
      in the pathogenesis of CsA nephrotoxicity and that spironolactone could be a
      useful agent to prevent it. These studies and the use of mineralocorticoid
      receptor blockade are discussed.

PMID- 17429035
TI  - Characterization of renin-angiotensin system enzyme activities in cultured mouse
      podocytes.
AB  - Intraglomerular ANG II has been linked to glomerular injury. However, little is
      known about the contribution of podocytes (POD) to intraglomerular ANG II
      homeostasis. The aim of the present study was to examine the processing of
      angiotensin substrates by cultured POD. Our approach was to use matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for
      peptide determination from conditioned cell media and customized AQUA peptides
      for quantification. Immortalized mouse POD were incubated with 1-2 microM ANG I,
      ANG II, or the renin substrate ANG-(1-14) for different time intervals and
      coincubated in parallel with various inhibitors. Human mesangial cells (MES) were
      used as controls. POD incubated with 1 microM ANG I primarily formed ANG-(1-9)
      and ANG-(1-7). In contrast, MES incubated with ANG I primarily generated ANG II.
      In POD, ANG-(1-7) was the predominant product, and its formation was inhibited by
      a neprilysin inhibitor. Modest angiotensin-converting enzyme (ACE) activity was
      also detected in POD, although only after cells were incubated with 2 microM ANG
      I. In addition, we observed that POD degraded ANG II into ANG III and ANG-(1-7).
      An aminopeptidase A inhibitor inhibited ANG III formation, and an ACE2 inhibitor
      led to ANG II accumulation. Furthermore, we found that POD converted ANG-(1-14)
      to ANG I and ANG-(1-7). This conversion was inhibited by a renin inhibitor. These
      findings demonstrate that POD express a functional intrinsic renin-angiotensin
      system characterized by neprilysin, aminopeptidase A, ACE2, and renin activities,
      which predominantly lead to ANG-(1-7) and ANG-(1-9) formation, as well as ANG II
      degradation. These findings may reflect a specific role of POD in maintenance of
      intraglomerular renin-angiotensin system balance.

PMID- 17429036
TI  - Effect of divalent heavy metals on epithelial Na+ channels in A6 cells.
AB  - To better understand how renal Na(+) reabsorption is altered by heavy metal
      poisoning, we examined the effects of several divalent heavy metal ions (Zn(2+),
      Ni(2+), Cu(2+), Pb(2+), Cd(2+), and Hg(2+)) on the activity of single epithelial
      Na(+) channels (ENaC) in a renal epithelial cell line (A6). None of the cations
      changed the single-channel conductance. However, ENaC activity [measured as the
      number of channels (N) x open probability (P(o))] was decreased by Cd(2+) and
      Hg(2+) and increased by Cu(2+), Zn(2+), and Ni(2+) but was not changed by Pb(2+).
      Of the cations that induced an increase in Na(+) channel function, Zn(2+)
      increased N, Ni(2+) increased P(o), and Cu(2+) increased both. The cysteine
      modification reagent [2-(trimethylammonium)ethyl]methanethiosulfonate bromide
      also increased N, whereas diethylpyrocarbonate, which covalently modifies
      histidine residues, affected neither P(o) nor N. Cu(2+) increased N and
      stimulated P(o) by reducing Na(+) self-inhibition. Furthermore, we observed that
      ENaC activity is slightly voltage dependent and that the voltage dependence of
      ENaC is insensitive to extracellular Na(+) concentration; however, apical
      application of Ni(2+) or diethylpyrocarbonate reduced the channel voltage
      dependence. Thus the voltage sensor of Xenopus ENaC is different from that of
      typical voltage-gated channels, since voltage appears to be sensed by histidine
      residues in the extracellular loops of ENaC, rather than by charged amino acids
      in a transmembrane domain.

PMID- 17429037
TI  - Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial
      infarction, and atrial fibrillation.
AB  - Rhythmic and effective cardiac contraction depends on appropriately timed
      generation and spread of cardiac electrical activity. The basic cellular unit of
      such activity is the action potential, which is shaped by specialized proteins
      (channels and transporters) that control the movement of ions across cardiac cell
      membranes in a highly regulated fashion. Cardiac disease modifies the operation
      of ion channels and transporters in a way that promotes the occurrence of cardiac
      rhythm disturbances, a process called "arrhythmogenic remodeling." Arrhythmogenic
      remodeling involves alterations in ion channel and transporter expression,
      regulation and association with important protein partners, and has important
      pathophysiological implications that contribute in major ways to cardiac
      morbidity and mortality. We review the changes in ion channel and transporter
      properties associated with three important clinical and experimental paradigms:
      congestive heart failure, myocardial infarction, and atrial fibrillation. We pay
      particular attention to K+, Na+, and Ca2+ channels; Ca2+ transporters; connexins;
      and hyperpolarization-activated nonselective cation channels and discuss the
      mechanisms through which changes in ion handling processes lead to cardiac
      arrhythmias. We highlight areas of future investigation, as well as important
      opportunities for improved therapeutic approaches that are being opened by an
      improved understanding of the mechanisms of arrhythmogenic remodeling.

PMID- 17429039
TI  - Disordered lipid metabolism and the pathogenesis of insulin resistance.
AB  - Although abnormal glucose metabolism defines type 2 diabetes mellitus (T2DM) and
      accounts for many of its symptoms and complications, efforts to understand the
      pathogenesis of T2DM are increasingly focused on disordered lipid metabolism.
      Here we review recent human studies exploring the mechanistic links between
      disorders of fatty acid/lipid metabolism and insulin resistance. As "mouse models
      of insulin resistance" were comprehensively reviewed in Physiological Reviews by
      Nandi et al. in 2004, we will concentrate on human studies involving the use of
      isotopes and/or magnetic resonance spectroscopy, occasionally drawing on mouse
      models which provide additional mechanistic insight.

PMID- 17429041
TI  - Restoration of barrier function in injured intestinal mucosa.
AB  - Mucosal repair is a complex event that immediately follows acute injury induced
      by ischemia and noxious luminal contents such as bile. In the small intestine,
      villous contraction is the initial phase of repair and is initiated by
      myofibroblasts that reside immediately beneath the epithelial basement membrane.
      Subsequent events include crawling of healthy epithelium adjacent to the wound,
      referred to as restitution. This is a highly regulated event involving signaling
      via basement membrane integrins by molecules such as focal adhesion kinase and
      growth factors. Interestingly, however, ex vivo studies of mammalian small
      intestine have revealed the importance of closure of the interepithelial tight
      junctions and the paracellular space. The critical role of tight junction closure
      is underscored by the prominent contribution of the paracellular space to
      measures of barrier function such as transepithelial electrical resistance.
      Additional roles are played by subepithelial cell populations, including
      neutrophils, related to their role in innate immunity. The net result of
      reparative mechanisms is remarkably rapid closure of mucosal wounds in mammalian
      tissues to prevent the onset of sepsis.

PMID- 17429040
TI  - Cardiac myocyte cell cycle control in development, disease, and regeneration.
AB  - Cardiac myocytes rapidly proliferate during fetal life but exit the cell cycle
      soon after birth in mammals. Although the extent to which adult cardiac myocytes
      are capable of cell cycle reentry is controversial and species-specific
      differences may exist, it appears that for the vast majority of adult cardiac
      myocytes the predominant form of growth postnatally is an increase in cell size
      (hypertrophy) not number. Unfortunately, this limits the ability of the heart to
      restore function after any significant injury. Interest in novel regenerative
      therapies has led to the accumulation of much information on the mechanisms that
      regulate the rapid proliferation of cardiac myocytes in utero, their cell cycle
      exit in the perinatal period, and the permanent arrest (terminal differentiation)
      in adult myocytes. The recent identification of cardiac progenitor cells capable
      of giving rise to cardiac myocyte-like cells has challenged the dogma that the
      heart is a terminally differentiated organ and opened new prospects for cardiac
      regeneration. In this review, we summarize the current understanding of
      cardiomyocyte cell cycle control in normal development and disease. In addition,
      we also discuss the potential usefulness of cardiomyocyte self-renewal as well as
      feasibility of therapeutic manipulation of the cardiac myocyte cell cycle for
      cardiac regeneration.

PMID- 17429042
TI  - The angiotensin II AT1 receptor structure-activity correlations in the light of
      rhodopsin structure.
AB  - The most prevalent physiological effects of ANG II, the main product of the renin
      angiotensin system, are mediated by the AT1 receptor, a rhodopsin-like AGPCR.
      Numerous studies of the cardiovascular effects of synthetic peptide analogs
      allowed a detailed mapping of ANG II's structural requirements for receptor
      binding and activation, which were complemented by site-directed mutagenesis
      studies on the AT1 receptor to investigate the role of its structure in ligand
      binding, signal transduction, phosphorylation, binding to arrestins,
      internalization, desensitization, tachyphylaxis, and other properties. The
      knowledge of the high-resolution structure of rhodopsin allowed homology modeling
      of the AT1 receptor. The models thus built and mutagenesis data indicate that
      physiological (agonist binding) or constitutive (mutated receptor) activation may
      involve different degrees of expansion of the receptor's central cavity. Residues
      in ANG II structure seem to control these conformational changes and to dictate
      the type of cytosolic event elicited during the activation. 1) Agonist aromatic
      residues (Phe8 and Tyr4) favor the coupling to G protein, and 2) absence of these
      residues can favor a mechanism leading directly to receptor internalization via
      phosphorylation by specific kinases of the receptor's COOH-terminal Ser and Thr
      residues, arrestin binding, and clathrin-dependent coated-pit vesicles. On the
      other hand, the NH2-terminal residues of the agonists ANG II and [Sar1]-ANG II
      were found to bind by two distinct modes to the AT1 receptor extracellular site
      flanked by the COOH-terminal segments of the EC-3 loop and the NH2-terminal
      domain. Since the [Sar1]-ligand is the most potent molecule to trigger
      tachyphylaxis in AT1 receptors, it was suggested that its corresponding binding
      mode might be associated with this special condition of receptors.

PMID- 17429038
TI  - Calcium and arrhythmogenesis.
AB  - Triggered activity in cardiac muscle and intracellular Ca2+ have been linked in
      the past. However, today not only are there a number of cellular proteins that
      show clear Ca2+ dependence but also there are a number of arrhythmias whose
      mechanism appears to be linked to Ca2+-dependent processes. Thus we present a
      systematic review of the mechanisms of Ca2+ transport (forward excitation
      contraction coupling) in the ventricular cell as well as what is known for other
      cardiac cell types. Second, we review the molecular nature of the proteins that
      are involved in this process as well as the functional consequences of both
      normal and abnormal Ca2+ cycling (e.g., Ca2+ waves). Finally, we review what we
      understand to be the role of Ca2+ cycling in various forms of arrhythmias, that
      is, those associated with inherited mutations and those that are acquired and
      resulting from reentrant excitation and/or abnormal impulse generation (e.g.,
      triggered activity). Further solving the nature of these intricate and dynamic
      interactions promises to be an important area of research for a better
      recognition and understanding of the nature of Ca2+ and arrhythmias. Our
      solutions will provide a more complete understanding of the molecular basis for
      the targeted control of cellular calcium in the treatment and prevention of such.

PMID- 17429044
TI  - Physiology and pathophysiology of purinergic neurotransmission.
AB  - This review is focused on purinergic neurotransmission, i.e., ATP released from
      nerves as a transmitter or cotransmitter to act as an extracellular signaling
      molecule on both pre- and postjunctional membranes at neuroeffector junctions and
      synapses, as well as acting as a trophic factor during development and
      regeneration. Emphasis is placed on the physiology and pathophysiology of ATP,
      but extracellular roles of its breakdown product, adenosine, are also considered
      because of their intimate interactions. The early history of the involvement of
      ATP in autonomic and skeletal neuromuscular transmission and in activities in the
      central nervous system and ganglia is reviewed. Brief background information is
      given about the identification of receptor subtypes for purines and pyrimidines
      and about ATP storage, release, and ectoenzymatic breakdown. Evidence that ATP is
      a cotransmitter in most, if not all, peripheral and central neurons is presented,
      as well as full accounts of neurotransmission and neuromodulation in autonomic
      and sensory ganglia and in the brain and spinal cord. There is coverage of neuron
      glia interactions and of purinergic neuroeffector transmission to nonmuscular
      cells. To establish the primitive and widespread nature of purinergic
      neurotransmission, both the ontogeny and phylogeny of purinergic signaling are
      considered. Finally, the pathophysiology of purinergic neurotransmission in both
      peripheral and central nervous systems is reviewed, and speculations are made
      about future developments.

PMID- 17429045
TI  - A new perspective for the treatment of renal diseases?

PMID- 17429046
TI  - Enzyme replacement therapy and Fabry kidney disease: quo vadis?

PMID- 17429047
TI  - Polycystic kidney disease.

PMID- 17429048
TI  - Autosomal dominant polycystic kidney disease: time for a change?
AB  - Diagnosis and treatment of autosomal dominant polycystic kidney disease (ADPKD)
      is rapidly changing. Cellular pathways that involve the polycystins are being
      mapped and involve the primary cilium, intracellular calcium and cAMP regulation,
      and the mammalian target of rapamycin (mTOR) pathway. With the use of new imaging
      approaches, earlier diagnosis of hepatic cystic disease is possible, and
      measurement of kidney and cystic growth as well as kidney blood flow is possible
      over relatively short periods. PKD gene type, gender, proteinuria, and the
      presence of hypertension relate to the rate of kidney growth in ADPKD. On the
      basis of risk factors for progression to ESRD and the pathogenic roles that
      intracellular cAMP and mTOR play in cystogenesis, novel therapies are now being
      tested, including maximal inhibition of the renin-angiotensin system, inhibition
      of renal intracellular cAMP using vasopressin V2 receptor antagonists, and
      somatostatin analogues, as well as inhibitors of mTOR. This review addresses the
      current understanding of the pathogenesis and the natural history of ADPKD;
      accuracy and reliability of diagnostic approaches in utero, childhood, and
      adulthood; the value of reliable magnetic resonance imaging to measure disease
      progression early in the course of ADPKD; and novel therapeutic approaches that
      are being evaluated in ADPKD.

PMID- 17429049
TI  - Genotype-phenotype correlations in autosomal dominant and autosomal recessive
      polycystic kidney disease.
AB  - The phenotypes that are associated with the common forms of polycystic kidney
      disease (PKD)--autosomal dominant (ADPKD) and autosomal recessive (ARPKD)--are
      highly variable in penetrance. This is in terms of severity of renal disease,
      which can range from neonatal death to adequate function into old age,
      characteristics of the liver disease, and other extrarenal manifestations in
      ADPKD. Influences of the germline mutation are at the genic and allelic levels,
      but intrafamilial variability indicates that genetic background and environmental
      factors are also key. In ADPKD, the gene involved, PKD1 or PKD2, is a major
      factor, with ESRD occurring 20 yr later in PKD2. Mutation position may also be
      significant, especially in terms of the likelihood of vascular events, with 5'
      mutations most detrimental. Variance component analysis in ADPKD populations
      indicates that genetic modifiers are important, but few such factors (beyond co
      inheritance of a TSC2 mutation) have been identified. Hormonal influences,
      especially associated with more severe liver disease in female individuals,
      indicate a role for nongenetic factors. In ARPKD, the combination of mutations is
      critical to the phenotypic outcome. Patients with two truncating mutations have a
      lethal phenotype, whereas the presence of at least one missense change can be
      compatible with life, indicating that many missense changes are hypomorphic
      alleles that generate partially functional protein. Clues from animal models and
      other forms of PKD highlight potential modifiers. The information that is now
      available on both genes is of considerable prognostic value with the prospects
      from the ongoing genetic revolution that additional risk factors will be
      revealed.

PMID- 17429043
TI  - Inositol trisphosphate receptor Ca2+ release channels.
AB  - The inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are a family of Ca2+
      release channels localized predominately in the endoplasmic reticulum of all cell
      types. They function to release Ca2+ into the cytoplasm in response to InsP3
      produced by diverse stimuli, generating complex local and global Ca2+ signals
      that regulate numerous cell physiological processes ranging from gene
      transcription to secretion to learning and memory. The InsP3R is a calcium
      selective cation channel whose gating is regulated not only by InsP3, but by
      other ligands as well, in particular cytoplasmic Ca2+. Over the last decade,
      detailed quantitative studies of InsP3R channel function and its regulation by
      ligands and interacting proteins have provided new insights into a remarkable
      richness of channel regulation and of the structural aspects that underlie signal
      transduction and permeation. Here, we focus on these developments and review and
      synthesize the literature regarding the structure and single-channel properties
      of the InsP3R.

PMID- 17429050
TI  - Wnt signaling in polycystic kidney disease.
AB  - Wnt signaling cascades activate morphogenetic programs that range from cell
      migration and proliferation to cell fate determination and stem cell renewal.
      These pathways enable cells to translate environmental cues into the complex
      cellular programs that are needed to organize tissues and build organs. Wnt
      signaling is essential for renal development; however, the specific molecular
      underpinnings involved are poorly understood. Recent research has revealed an
      unexpected intersection between Wnt signaling and polycystic kidney disease. Some
      polycystic kidney disease proteins, such as Inversin and Bardet-Biedl syndrome
      family members, were found to use components of the Wnt signaling cascade to
      orient cells along a secondary polarity axis within the plane of the epithelium.
      These spatial cues may be needed to position nascent tubules with a defined
      geometry.

PMID- 17429051
TI  - Role of primary cilia in the pathogenesis of polycystic kidney disease.
AB  - Cysts in the kidney are among the most common inherited human pathologies, and
      recent research has uncovered that a defect in cilia-mediated signaling activity
      is a key factor that leads to cyst formation. The cilium is a microtubule-based
      organelle that is found on most cells in the mammalian body. Multiple proteins
      whose functions are disrupted in cystic diseases have now been localized to the
      cilium or at the basal body at the base of the cilium. Current data indicate that
      the cilium can function as a mechanosensor to detect fluid flow through the lumen
      of renal tubules. Flow-mediated deflection of the cilia axoneme induces an
      increase in intracellular calcium and alters gene expression. Alternatively, a
      recent finding has revealed that the intraflagellar transport 88/polaris protein,
      which is required for cilia assembly, has an additional role in regulating cell
      cycle progression independent of its function in ciliogenesis. Further research
      directed at understanding the relationship between the cilium, cell-cycle, and
      cilia-mediated mechanosensation and signaling activity will hopefully provide
      important insights into the mechanisms of renal cyst pathogenesis and lead to
      better approaches for therapeutic intervention.

PMID- 17429052
TI  - Acidosis-sensing glutamine pump SNAT2 determines amino acid levels and mammalian
      target of rapamycin signalling to protein synthesis in L6 muscle cells.
AB  - Wasting of lean tissue as a consequence of metabolic acidosis is a serious
      problem in patients with chronic renal failure. A possible contributor is
      inhibition by low pH of the System A (SNAT2) transporter, which carries the amino
      acid L-glutamine (L-Gln) into muscle cells. The aim of this study was to
      determine the effect of selective SNAT2 inhibition on intracellular amino acid
      profiles and amino acid-dependent signaling through mammalian target of rapamycin
      in L6 skeletal muscle cells. Inhibition of SNAT2 with the selective competitive
      substrate methylaminoisobutyrate, metabolic acidosis (pH 7.1), or silencing SNAT2
      expression with small interfering RNA all depleted intracellular L-Gln. SNAT2
      inhibition also indirectly depleted other amino acids whose intracellular
      concentrations are maintained by the L-Gln gradient across the plasma membrane,
      notably the anabolic amino acid L-leucine. Consequently, SNAT2 inhibition
      strongly impaired signaling through mammalian target of rapamycin to ribosomal
      protein S6 kinase, ribosomal protein S6, and 4E-BP1, leading to impairment of
      protein synthesis comparable with that induced by rapamycin. It is concluded that
      even though SNAT2 is only one of several L-Gln transporters in muscle, it may
      determine intracellular anabolic amino acid levels, regulating the amino acid
      signaling that affects protein mass, nucleotide/nucleic acid metabolism, and cell
      growth.

PMID- 17429053
TI  - Hepatitis C virus and death risk in hemodialysis patients.
AB  - In maintenance hemodialysis (MHD) patients, hepatitis C virus (HCV) infection is
      common and may be associated with poor clinical outcomes. It was hypothesized
      that HCV infection would be associated with high all-cause and cardiovascular
      mortality in these patients after controlling for demographic and clinical
      characteristics, including surrogates of malnutrition-inflammation complex
      syndrome. A national database of 13,664 MHD patients who underwent HCV antibody
      serology testing at least once during a 3-yr interval (July 2001 through June
      2004) was analyzed. Measurements included third-generation HCV enzyme immunoassay
      and routine laboratory measurements. The HCV enzyme immunoassay was reported
      positive in 1590 (12%) patients. In logistic regression models that included case
      mix and available surrogates of malnutrition-inflammation complex syndrome, HCV
      infection was associated with younger age, male gender, black race, Hispanic
      ethnicity, Medicaid insurance, longer dialysis vintage (duration), unmarried
      status, HIV infection, and smoking history. In proportional-hazards regressions,
      the mortality hazard ratio that was associated with HCV infection was 1.25 (95%
      confidence interval 1.12 to 1.39; P < 0.001). Mortality hazards were higher among
      incident (dialysis duration <6 mo) than prevalent HD patients. Subgroup analyses
      indicated that HCV was associated with higher all-cause and cardiovascular
      mortality across almost all clinical, demographic, and laboratory groups of
      patients. Hence, in MHD patients, HCV infection exhibits distinct demographic,
      clinical, and laboratory patterns, including associations with higher dialysis
      treatment vintage, and is associated with higher mortality. More diligent efforts
      to prevent and treat HCV infection may improve outcomes in MHD patients.

PMID- 17429054
TI  - Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats.
AB  - IL-13 has been implicated in the pathogenesis of minimal-change nephrotic
      syndrome. This study aimed to investigate the role of IL-13 on the development of
      proteinuria and expression of podocyte-related genes that are associated with
      nephrotic syndrome. IL-13 was overexpressed in Wistar rats through transfection
      of a mammalian expression vector cloned with the rat IL-13 gene, into the
      quadriceps by in vivo electroporation. Serum IL-13, albumin, cholesterol, and
      creatinine and urine albumin were measured serially. Kidneys were harvested after
      day 70 for histology and electron microscopy. Glomerular gene expression of
      nephrin, podocin, dystroglycan, B7-1, and IL-13 receptor subunits were examined
      using real-time PCR with hybridization probes and expressed as an index against
      beta-actin. Protein expression of these molecules was determined by
      immunofluorescence staining. The IL-13-transfected rats (n = 41) showed
      significant albuminuria, hypoalbuminemia, and hypercholesterolemia when compared
      with control rats (n = 17). No significant histologic changes were seen in
      glomeruli of IL-13-transfected rats. However, electron microscopy showed up to
      80% of podocyte foot process fusion. Glomerular gene expression was significantly
      upregulated for B7-1, IL-4Ralpha, and IL-13Ralpha2 but downregulated for nephrin,
      podocin, and dystroglycan. Immunofluorescence staining intensity was reduced for
      nephrin, podocin, and dystroglycan but increased for B7-1 and IL-4Ralpha in IL-13
      transfected rats compared with controls. In conclusion, these results suggest
      that IL-13 overexpression in the rat could lead to podocyte injury with
      downregulation of nephrin, podocin, and dystroglycan and a concurrent
      upregulation of B7-1 in the glomeruli, inducing a minimal change-like nephropathy
      that is characterized by increased proteinuria, hypoalbuminemia,
      hypercholesterolemia, and fusion of podocyte foot processes.

PMID- 17429056
TI  - Accelerated urinary excretion of methylmercury following administration of its
      antidote N-acetylcysteine requires Mrp2/Abcc2, the apical multidrug resistance
      associated protein.
AB  - N-Acetylcysteine (NAC) is a sulfhydryl-containing compound that produces a
      dramatic acceleration of urinary methylmercury (MeHg) excretion in poisoned mice,
      but the molecular mechanism for this effect is poorly defined. MeHg readily binds
      to NAC to form the MeHg-NAC complex, and recent studies indicate that this
      complex is an excellent substrate for the basolateral organic anion transporter
      (Oat)-1, Oat1/Slc22a6, thus potentially explaining the uptake from blood into the
      renal tubular cells. The present study tested the hypothesis that intracellular
      MeHg is subsequently transported across the apical membrane of the cells into the
      tubular fluid as a MeHg-NAC complex using the multidrug resistance-associated
      protein-2 (Mrp2/Abcc2). NAC markedly stimulated urinary [(14)C]MeHg excretion in
      wild-type Wistar rats, and a second dose of NAC was as effective as the first
      dose in stimulating MeHg excretion. In contrast with the normal Wistar rats, NAC
      was much less effective at stimulating urinary MeHg excretion in the Mrp2
      deficient (TR-) Wistar rats. The TR- rats excreted only approximately 30% of the
      MeHg excreted by the wild-type animals. To directly test whether MeHg-NAC is a
      substrate for Mrp2, studies were carried out in plasma membrane vesicles isolated
      from livers of TR- and control Wistar rats. Transport of MeHg-NAC was lower in
      vesicles prepared from TR- rats, whereas transport of MeHg-cysteine was similar
      in control and TR- rats. These results indicate that Mrp2 is involved in urinary
      MeHg excretion after NAC administration and suggest that the transported molecule
      is most likely the MeHg-NAC complex.

PMID- 17429055
TI  - Pax transactivation-domain interacting protein is required for urine
      concentration and osmotolerance in collecting duct epithelia.
AB  - Pax transactivation-domain interacting protein (PTIP) is a widely expressed
      nuclear protein that is essential for early embryonic development. PTIP was first
      identified on the basis of its interactions with the developmental regulator Pax2
      but can also bind to other nuclear transcription factors. The Pax2 protein is
      essential for development of the renal epithelia and for regulating the response
      of mature collecting ducts to hyperosmotic stress. For determination of whether
      PTIP also functions in more differentiated cell types, the Cre-LoxP system was
      used to delete the ptip gene in the renal collecting ducts using Ksp-Cre driver
      mice. Collecting duct-specific ptip knockout mice were viable with little
      discernible phenotype under normal physiologic conditions. However, collecting
      duct-specific ptip mutants were unable to concentrate urine after the treatment
      of desamino-cis, D-arginine vasopressin, an antidiuretic hormone. Furthermore,
      aquaporin-2 (AQP2) expression in the inner medulla of the ptip knockout mice was
      decreased approximately 10-fold compared with that of wild-type littermates.
      Expression level of tonicity responsive enhancer binding protein, a transcription
      factor of AQP2, is not altered in the mutant mice, but its nuclear localization
      in the inner medulla is unresponsive after treatment with vasopressin agonists.
      This was due, at least in part, to decreased expression of the arginine
      vasopressin receptor 2 in ptip mutants. Furthermore, ptip null inner medullary
      collecting duct cells were sensitive to hyperosmolality in vitro. Thus, ptip is
      required for the urine concentration mechanism by modulating arginine vasopressin
      receptor 2 and AQP2 expression in the inner medulla. The data suggest an
      essential role for ptip in regulating urine concentration and in controlling
      survival of collecting duct epithelial cells in high osmolality.

PMID- 17429057
TI  - Modulation of sympathetic activity by tissue plasminogen activator is independent
      of plasminogen and urokinase.
AB  - Sympathetic neurons synthesize, transport, and release tissue-type plasminogen
      activators (t-PAs) and urinary-type plasminogen activators (u-PAs). We reported
      that t-PA enhances sympathetic neurotransmission and exacerbates reperfusion
      arrhythmias. We have now assessed the role of u-PA and plasminogen. Neurogenic
      contractile responses to electrical field stimulation (EFS) were determined in
      vasa deferentia (VD) from mice lacking t-PA (t-PA(-/-)), plasminogen activator
      inhibitor-1 (PAI-1(-/-)), plasminogen (plgn(-/-)), u-PA (u-PA(-/-)), and wild
      type (WT) controls. Similar levels of t-PA were present in VD and cardiac
      synaptosomes of WT, PAI-1(-/-), plgn(-/-), and u-PA(-/-) mice, whereas t-PA was
      undetectable in t-PA(-/-) tissues. EFS responses were potentiated and attenuated
      in VD from PAI-1(-/-) and t-PA(-/-) mice, respectively, but indistinguishable
      from WT responses in VD from plgn(-/-) and u-PA(-/-) mice. Moreover, t-PA
      inhibition with t-PA(stop) decreased EFS response in WT mice, whereas u-PA(stop)
      did not. VD responses to ATP, norepinephrine, and K(+) in t-PA(-/-), PAI-1(-/-),
      plgn(-/-), and u-PA(-/-) mice were similar to those in WT, whereas t-PA(stop) did
      not modify VD responses to norepinephrine in WT, t-PA(-/-), and PAI-1(-/-) mice,
      indicating a prejunctional site of action for t-PA-induced potentiation of
      sympathetic neurotransmission. Indeed, K(+)-induced norepinephrine exocytosis
      from cardiac synaptosomes was potentiated in PAI-1(-/-), attenuated in t-PA(-/-)
      and not different from WT in u-PA(-/-) and plgn(-/-) mice. Likewise, ATP
      exocytosis was decreased in t-PA(-/-) and attenuated by t-PA(stop) in WT mice.
      Thus, t-PA-induced enhancement of sympathetic neurotransmission is a
      prejunctional event associated with increased transmitter exocytosis and
      independent of u-PA and plasminogen availability. This novel t-PA action may be a
      potential therapeutic target in hyperadrenergic states.

PMID- 17429058
TI  - Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a radical scavenger, prevents 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in the
      substantia nigra but not the striatum.
AB  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal
      dopaminergic neurotoxicity and behavioral impairment in rodents, and previous
      studies suggest that nitric oxide and reactive oxygen species are involved in
      MPTP-induced neurotoxicity. The present study examines the effect of edaravone (3
      methyl-1-phenyl-2-pyrazolin-5-one), a radical scavenger, on MPTP-induced
      neurotoxicity in the striatum and substantia nigra pars compacta (SNc) of
      C57BL/6J mice. MPTP treatment (10 mg/kg s.c. x 4 with 2-h intervals) decreased
      dopamine levels and tyrosine hydroxylase immunostaining in the striatum and SNc.
      Pretreatment with edaravone (1 and 3 mg/kg i.p.) significantly reduced the
      neurotoxicity in the SNc but not striatum. An immunohistochemical study showed
      that MPTP caused microglial activation both in the striatum and SNc, whereas it
      increased 3-nitrotyrosine immunoreactivity, an in vivo biomarker of peroxynitrite
      production, in the SNc but not the striatum. Furthermore, MPTP increased lipid
      peroxidation product thiobarbituric acid reactive substance in the midbrain, but
      not the striatum. Edaravone inhibited activation of the microglia and the
      increased 3-nitrotyrosine immunoreactivity in the SNc but not the striatum, and
      it also inhibited thiobarbituric acid reactive substance levels in the midbrain.
      Behavioral analyses showed that edaravone improved MPTP-induced impairment of
      locomotion and Rotorod performance. These results suggest that edaravone protects
      against MPTP-induced neurotoxicity in the SNc by blocking the production of
      reactive oxygen species or peroxynitrite and imply that dopaminergic degeneration
      in the SNc may play an important role in MPTP-induced motor dysfunction of mice.

PMID- 17429059
TI  - A prospective study of overall diet quality and risk of type 2 diabetes in women.
AB  - OBJECTIVE: The aim of this article was to assess the association between the
      Alternate Healthy Eating Index (AHEI) and risk of type 2 diabetes in women.
      RESEARCH DESIGN AND METHODS: A total of 80,029 women aged 38-63 years in the
      Nurses' Health Study were followed from 1984 to 2002. The AHEI score was computed
      from dietary information collected from five repeated food frequency
      questionnaires administered between 1984 and 1998. Relative risks (RRs) for type
      2 diabetes were calculated using Cox proportional hazards models and adjusted for
      known diabetes risk factors. We also examined how changes in score in 4, 6-8, and
      10-12 years are associated with diabetes risk. RESULTS: We ascertained 5,183
      incident cases of type 2 diabetes during 18 years of follow-up. Women who scored
      high on the AHEI had a lower risk (RR comparing top to bottom score quintile 0.64
      [95% CI 0.58-0.71], P(trend) < 0.0001) for diabetes. Women with consistently high
      AHEI scores throughout follow-up, compared with those with consistently low
      scores, had the lowest risk for diabetes. In addition, women whose AHEI scores
      improved during follow-up, even during recent years, had a lower risk of diabetes
      than did women whose (low) score did not change. CONCLUSIONS: A higher AHEI score
      is associated with a lower risk of type 2 diabetes in women. Therefore, the AHEI
      score may be a useful clinical tool to assess diet quality and to recommend for
      the prevention of diabetes.

PMID- 17429060
TI  - Alanine aminotransferase and directly measured insulin sensitivity in a
      multiethnic cohort: the Insulin Resistance Atherosclerosis Study.
AB  - OBJECTIVE: The objective of the present analysis was to evaluate the association
      of alanine aminotransferase (ALT) with directly measured insulin sensitivity
      (S(i)) in a large, multiethnic cohort of U.S. adults and to determine whether ALT
      adds to existing metabolic risk definitions in identifying subjects with insulin
      resistance. RESEARCH DESIGN AND METHODS: S(i) was directly measured from
      frequently sampled intravenous glucose tolerance tests among 999 nondiabetic
      African-American, Hispanic, and non-Hispanic white subjects aged 40-69 years who
      were participating in the Insulin Resistance Atherosclerosis Study. Subjects also
      received an oral glucose tolerance test, and fasting insulin, ALT, and alcohol
      intake were determined. RESULTS: ALT was associated with S(i) after adjustment
      for age, sex, ethnicity, impaired fasting glucose, triglycerides, HDL, blood
      pressure, and waist (clinical model) (P < 0.0001). The association remained
      significant after further adjustment for fasting insulin and impaired glucose
      tolerance (P = 0.004). In logistic regression analysis, elevated ALT (upper
      quartile) was associated with insulin resistance (lowest quartile of S(i)) after
      adjustment for age, sex, and ethnicity (odds ratio 3.0 [95% CI 2.2-4.1]).
      Elevated ALT was independently associated with insulin resistance when included
      in models with waist circumference, National Cholesterol Education Program
      criteria for metabolic syndrome, hypertriglyceridemic waist, elevated
      triglyceride-to-HDL ratio, or homeostasis model assessment of insulin resistance
      (HOMA-IR) (all P < 0.01). Finally, the addition of elevated ALT improved
      classification of insulin resistance by area under the receiver operating
      characteristic curve criteria for all models except HOMA-IR. CONCLUSIONS: ALT was
      associated with insulin resistance independently of conventional and more
      detailed metabolic measures. These findings suggest that the addition of ALT to
      existing clinically based metabolic risk definitions is an inexpensive way to
      improve the identification of subjects with insulin resistance.

PMID- 17429061
TI  - Disparities in diabetes care between smokers and nonsmokers.

PMID- 17429062
TI  - Primary aldosteronism in diabetic subjects with resistant hypertension.
AB  - OBJECTIVE: Despite the high prevalence of hypertension in patients with type 2
      diabetes, the prevalence of primary aldosteronism in this population has not been
      determined. RESEARCH DESIGN AND METHODS: One hundred subjects with type 2
      diabetes and resistant hypertension, defined as blood pressure > 140/90 mmHg
      despite the use of > or = 3 antihypertensive agents, were screened for primary
      aldosteronism. Screening was performed by measuring the plasma aldosterone (PAC)
      to-plasma renin activity (PRA) ratio. Subjects with a PAC-to-PRA ratio > 30 ng x
      ml(-1) x h(-1) underwent confirmatory salt load testing. Diagnostic criteria
      included 24-h urine aldosterone > or = 12 microg during the 3rd day of the oral
      salt load or a PAC > or = 5 ng/dl after the 4-h intravenous saline load. RESULTS:
      Thirty-four subjects had a PAC-to-PRA ratio >30 ng x ml(-1) x h(-1). Fourteen
      subjects (14% [95% CI 7.2-20.8]) had a confirmed diagnosis of primary
      aldosteronism. Ninety-three patients were African Americans. There were no
      differences in age, glycemic control, and number of antihypertensive drugs
      between subjects with and without primary aldosteronism. Subjects with primary
      aldosteronism had lower serum potassium (3.7 +/- 0.4 vs. 4.0 +/- 0.4 mmol/l, P =
      0.012), higher PAC (15.6 +/- 8 vs. 9.1 +/- 6 ng/dl, P = 0.0016), and higher PAC
      to-PRA ratio (98 +/- 74 vs. 21 +/- 30 x ml(-1) x h(-1), P < 0.001) than patients
      without primary aldosteronism. CONCLUSIONS: Primary aldosteronism is common in
      diabetic patients with resistant hypertension, with a prevalence of 14%. Our
      results indicate that diabetic subjects with poorly controlled hypertension who
      are taking > or = 3 antihypertensive drugs should be screened for primary
      aldosteronism.

PMID- 17429063
TI  - The role of iron in diabetes and its complications.

PMID- 17429064
TI  - Fission yeast Taz1 and RPA are synergistically required to prevent rapid telomere
      loss.
AB  - The telomere complex must allow nucleases and helicases to process chromosome
      ends to make them substrates for telomerase, while preventing these same
      activities from disrupting chromosome end-protection. Replication protein A (RPA)
      binds to single-stranded DNA and is required for DNA replication, recombination,
      repair, and telomere maintenance. In fission yeast, the telomere binding protein
      Taz1 protects telomeres and negatively regulates telomerase. Here, we show that
      taz1-d rad11-D223Y double mutants lose their telomeric DNA, indicating that RPA
      (Rad11) and Taz1 are synergistically required to prevent telomere loss. Telomere
      loss in the taz1-d rad11-D223Y double mutants was suppressed by additional
      mutation of the helicase domain in a RecQ helicase (Rqh1), or by overexpression
      of Pot1, a single-strand telomere binding protein that is essential for
      protection of chromosome ends. From our results, we propose that in the absence
      of Taz1 and functional RPA, Pot1 cannot function properly and the helicase
      activity of Rqh1 promotes telomere loss. Our results suggest that controlling the
      activity of Rqh1 at telomeres is critical for the prevention of genomic
      instability.

PMID- 17429065
TI  - Cx43 mediates TGF-beta signaling through competitive Smads binding to
      microtubules.
AB  - Transforming growth factor-beta (TGF-beta) superfamily members play an important
      role in growth, differentiation, adhesion, apoptosis, and development in many
      species from insects and worms to vertebrates. Recently, TGF-beta signaling has
      been demonstrated to be negatively regulated by microtubules (MTs), which anchor
      endogenous Smad2/3 to cytosol and also directly interact with connexin43 (Cx43),
      and the activity of TGF-beta is mediated by Cx43. However, the mechanism
      underlying the intracellular regulation of TGF-beta activity by Cx43 remains
      unknown. Here, we found that the functional link between TGF-beta activation and
      Cx43 is mediated by interactions among Smad2/3, MTs, and Cx43. We confirmed that
      Cx43 competes with Smad2/3 for binding to MTs, which Cx43 specifically induces
      release of Smad2/3 from MTs and increases phospho-Smad2 and which, as a result,
      Smad2/3 and Smad4 are accumulated in the nucleus, leading to activation of the
      transcription of target genes. Consistently, knockdown of the endogenous Cx43
      activity with double-strand RNA (dsRNA) in HL1 cardiomyocytes and Cx43 knockout
      mice cardiomyocytes consistently show the opposite effect. Our findings
      demonstrate a novel mechanism for Cx43 positive regulation of TGF-beta function.

PMID- 17429066
TI  - Increased apoptosis and skewed differentiation in mouse embryonic stem cells
      lacking the histone methyltransferase Mll2.
AB  - Epigenetic regulation by histone methyltransferases provides transcriptional
      memory and inheritable propagation of gene expression patterns. Potentially, the
      transition from a pluripotent state to lineage commitment also includes
      epigenetic instructions. The histone 3 lysine 4 methyltransferase Mll2/Wbp7 is
      essential for embryonic development. Here, we used embryonic stem (ES) cell lines
      deficient for Mll2 to examine its function more accurately. Mll2-/- ES cells are
      viable and retain pluripotency, but they display cell proliferation defects due
      to an enhanced rate of apoptosis. Apoptosis was not relieved by caspase
      inhibition and correlated with decreased Bcl2 expression. Concordantly, Mll2
      binds to the Bcl2 gene and H3K4me(3) levels are reduced at the binding site when
      Mll2 is absent. In vitro differentiation showed delays along representative
      pathways for all three germ layers. Although ectodermal delays were severe and
      mesodermal delays persisted at about three days, endodermal differentiation
      seemed to recover and overshoot, concomitant with prolonged Oct4 gene expression.
      Hence, Mll2 is not required for ES cell self-renewal or the complex changes in
      gene expression involved in lineage commitment, but it contributes to the
      coordination and timing of early differentiation decisions.

PMID- 17429067
TI  - Cell polarity development and protein trafficking in hepatocytes lacking E
      cadherin/beta-catenin-based adherens junctions.
AB  - Using a mutant hepatocyte cell line in which E-cadherin and beta-catenin are
      completely depleted from the cell surface, and, consequently, fail to form
      adherens junctions, we have investigated adherens junction requirement for apical
      basolateral polarity development and polarized membrane trafficking. It is shown
      that these hepatocytes retain the capacity to form functional tight junctions,
      develop full apical-basolateral cell polarity, and assemble a subapical cortical
      F-actin network, although with a noted delay and a defect in subsequent apical
      lumen remodeling. Interestingly, whereas hepatocytes typically target the plasma
      membrane protein dipeptidyl peptidase IV first to the basolateral surface,
      followed by its transcytosis to the apical domain, hepatocytes lacking E-cadherin
      based adherens junctions target dipeptidyl peptidase IV directly to the apical
      surface. Basolateral surface-directed transport of other proteins or lipids
      tested was not visibly affected in hepatocytes lacking E-cadherin-based adherens
      junctions. Together, our data show that E-cadherin/beta-catenin-based adherens
      junctions are dispensable for tight junction formation and apical lumen
      biogenesis but not for apical lumen remodeling. In addition, we suggest a
      possible requirement for E-cadherin/beta-catenin-based adherens junctions with
      regard to the indirect apical trafficking of specific proteins in hepatocytes.

PMID- 17429068
TI  - Rab1b interacts with GBF1 and modulates both ARF1 dynamics and COPI association.
AB  - Assembly of the cytosolic coat protein I (COPI) complex at the ER-Golgi interface
      is directed by the ADP ribosylation factor1 (Arf1) and its guanine nucleotide
      exchange factor (GBF1). Rab1b GTPase modulates COPI recruitment, but the
      molecular mechanism underlying this action remains unclear. Our data reveal that
      in vivo expression of the GTP-restricted Rab1b mutant (Rab1Q67L) increased the
      association of GBF1 and COPI to peripheral structures localized at the ER exit
      sites (ERES) interface. Active Rab1b also stabilized Arf1 on Golgi membranes.
      Furthermore, we characterized GBF1 as a new Rab1b effector, and showed that its N
      terminal domain was involved in this interaction. Rab1b small interfering RNA
      oligonucleotide assays suggested that Rab1b was required for GBF1 membrane
      association. To further understand how Rab1b functions in ER-to-Golgi transport,
      we analyzed GFP-Rab1b dynamics in HeLa cells. Time-lapse microscopy indicated
      that the majority of the Rab1b-labeled punctuated structures are relatively short
      lived with limited-range movements. FRAP of Golgi GFP-Rab1bwt showed rapid
      recovery (t(1/2) 120 s) with minimal dependence on microtubules. Our data support
      a model where Rab1b-GTP induces GBF1 recruitment at the ERES interface and at the
      Golgi complex where it is required for COPII/COPI exchange or COPI vesicle
      formation, respectively.

PMID- 17429069
TI  - Direct observation of regulated ribonucleoprotein transport across the nurse
      cell/oocyte boundary.
AB  - In Drosophila, the asymmetric localization of specific mRNAs to discrete regions
      within the developing oocyte determines the embryonic axes. The microtubule
      motors dynein and kinesin are required for the proper localization of the
      determinant ribonucleoprotein (RNP) complexes, but the mechanisms that account
      for RNP transport to and within the oocyte are not well understood. In this work,
      we focus on the transport of RNA complexes containing bicoid (bcd), an anterior
      determinant. We show in live egg chambers that, within the nurse cell
      compartment, dynein actively transports green fluorescent protein-tagged
      Exuperantia, a cofactor required for bcd RNP localization. Surprisingly, the loss
      of kinesin I activity elevates RNP motility in nurse cells, whereas disruption of
      dynein activity inhibits RNP transport. Once RNPs are transferred through the
      ring canal to the oocyte, they no longer display rapid, linear movements, but
      they are distributed by cytoplasmic streaming and gradually disassemble. By
      contrast, bcd mRNA injected into oocytes assembles de novo into RNP particles
      that exhibit rapid, dynein-dependent transport. We speculate that after delivery
      to the oocyte, RNP complexes may disassemble and be remodeled with appropriate
      accessory factors to ensure proper localization.

PMID- 17429070
TI  - Plc1p is required for SAGA recruitment and derepression of Sko1p-regulated genes.
AB  - In Saccharomyces cerevisiae, many osmotically inducible genes are regulated by
      the Sko1p-Ssn6p-Tup1p complex. On osmotic shock, the MAP kinase Hog1p associates
      with this complex, phosphorylates Sko1p, and converts it into an activator that
      subsequently recruits Swi/Snf and SAGA complexes. We have found that
      phospholipase C (Plc1p encoded by PLC1) is required for derepression of Sko1p
      Ssn6p-Tup1p-controlled osmoinducible genes upon osmotic shock. Although plc1Delta
      mutation affects the assembly of the preinitiation complex after osmotic shock,
      it does not affect the recruitment of Hog1p and Swi/Snf complex at these
      promoters. However, Plc1p facilitates osmotic shock-induced recruitment of the
      SAGA complex. Like plc1Delta cells, SAGA mutants are osmosensitive and display
      compromised expression of osmotically inducible genes. The reduced binding of
      SAGA to Sko1p-Ssn6p-Tup1p-repressed promoters in plc1Delta cells does not
      correlate with reduced histone acetylation. However, SAGA functions at these
      promoters to facilitate recruitment of the TATA-binding protein. The results thus
      provide evidence that Plc1p and inositol polyphosphates affect derepression of
      Sko1p-Ssn6p-Tup1p-controlled genes by a mechanism that involves recruitment of
      the SAGA complex and TATA-binding protein.

PMID- 17429071
TI  - The RING finger domain of MDM2 is essential for MDM2-mediated TGF-beta
      resistance.
AB  - In this study, we attempt to gain insights into the molecular mechanism
      underlying MDM2-mediated TGF-beta resistance. MDM2 renders cells refractory to
      TGF-beta by overcoming a TGF-beta-induced G1 cell cycle arrest. Because the TGF
      beta resistant phenotype is reversible upon removal of MDM2, MDM2 likely confers
      TGF-beta resistance by directly targeting the cellular machinery involved in the
      growth inhibition by TGF-beta. Investigation of the structure-function
      relationship of MDM2 reveals three elements essential for MDM2 to confer TGF-beta
      resistance in both mink lung epithelial cells and human mammary epithelial cells.
      One of these elements is the C-terminal half of the p53-binding domain, which at
      least partially retained p53-binding and inhibitory activity. Second, the ability
      of MDM2 to mediate TGF-beta resistance is disrupted by mutation of the nuclear
      localization signal, but is restored upon coexpression of MDMX. Finally,
      mutations of the zinc coordination residues of the RING finger domain abrogates
      TGF-beta resistance, but not the ability of MDM2 to inhibit p53 activity or to
      bind MDMX. These data suggest that RING finger-mediated p53 inhibition and MDMX
      interaction are not sufficient to cause TGF-beta resistance and imply a crucial
      role of the E3 ubiquitin ligase activity of this domain in MDM2-mediated TGF-beta
      resistance.

PMID- 17429072
TI  - RKIKK motif in the intracellular domain is critical for spatial and dynamic
      organization of ICAM-1: functional implication for the leukocyte adhesion and
      transmigration.
AB  - No direct evidence has been reported whether the spatial organization of ICAM-1
      on the cell surface is linked to its physiological function in terms of leukocyte
      adhesion and transendothelial migration (TEM). Here we observed that ICAM-1 by
      itself directly regulates the de novo elongation of microvilli and is thereby
      clustered on the microvilli. However, truncation of the intracellular domain
      resulted in uniform cell surface distribution of ICAM-1. Mutation analysis
      revealed that the C-terminal 21 amino acids are dispensable, whereas a segment of
      5 amino acids ((507)RKIKK(511)) in the NH-terminal third of intracellular domain,
      is required for the proper localization and dynamic distribution of ICAM-1 and
      the association of ICAM-1 with F-actin, ezrin, and moesin. Importantly, deletion
      of the (507)RKIKK(511) significantly delayed the LFA-1-dependent membrane
      projection and decreased leukocyte adhesion and subsequent TEM. Endothelial cells
      treated with cell-permeant penetratin-ICAM-1 peptides comprising ICAM-1 RKIKK
      sequences inhibited leukocyte TEM. Collectively, these findings demonstrate that
      (507)RKIKK(511) is an essential motif for the microvillus ICAM-1 presentation and
      further suggest a novel regulatory role for ICAM-1 topography in leukocyte TEM.

PMID- 17429073
TI  - Induction of vascular permeability: beta PIX and GIT1 scaffold the activation of
      extracellular signal-regulated kinase by PAK.
AB  - Increased permeability of blood vessels is an important component of
      inflammation, but in some circumstances it contributes to tissue injury and organ
      failure. Previous work showed that p21-activated kinase (PAK) is a critical
      regulator of endothelial cell-cell junctions through effects on myosin light
      chain phosphorylation and cell contractility. We now show that blocking PAK
      function inhibits fluid leak in a mouse model of acute lung injury. In cultured
      endothelial cells, induction of myosin light chain phosphorylation by PAK is
      mediated by mitogen-activated protein kinase kinase and extracellular signal
      regulated kinase (Erk). Erk in lipopolysaccharide (LPS)-treated mouse lung is
      activated in a PAK-dependent manner in several cell types, most prominently
      vascular endothelium. Activation of Erk requires the integrity of the complex
      between PAK, PIX, and GIT1. Several means of disrupting this complex inhibit
      stimulation of vascular permeability in vitro. A cell-permeant peptide that
      blocks binding of PAK to PIX inhibits LPS-induced fluid leak in the mouse lung
      injury model. We conclude that the PAK-PIX-GIT1 complex is critical for Erk
      dependent myosin phosphorylation and vascular permeability.

PMID- 17429074
TI  - Analysis of P-body assembly in Saccharomyces cerevisiae.
AB  - Recent experiments have defined cytoplasmic foci, referred to as processing
      bodies (P-bodies), that contain untranslating mRNAs in conjunction with proteins
      involved in translation repression and mRNA decapping and degradation. However,
      the order of protein assembly into P-bodies and the interactions that promote P
      body assembly are unknown. To gain insight into how yeast P-bodies assemble, we
      examined the P-body accumulation of Dcp1p, Dcp2p, Edc3p, Dhh1p, Pat1p, Lsm1p,
      Xrn1p, Ccr4p, and Pop2p in deletion mutants lacking one or more P-body component.
      These experiments revealed that Dcp2p and Pat1p are required for recruitment of
      Dcp1p and of the Lsm1-7p complex to P-bodies, respectively. We also demonstrate
      that P-body assembly is redundant and no single known component of P-bodies is
      required for P-body assembly, although both Dcp2p and Pat1p contribute to P-body
      assembly. In addition, our results indicate that Pat1p can be a nuclear
      cytoplasmic shuttling protein and acts early in P-body assembly. In contrast, the
      Lsm1-7p complex appears to primarily function in a rate limiting step after P
      body assembly in triggering decapping. Taken together, these results provide
      insight both into the function of individual proteins involved in mRNA
      degradation and the mechanisms by which yeast P-bodies assemble.

PMID- 17429075
TI  - The nucleolar channel system of human endometrium is related to endoplasmic
      reticulum and R-rings.
AB  - The nucleolar channel system (NCS) is a well-established ultrastructural hallmark
      of the postovulation endometrium. Its transient presence has been associated with
      human fertility. Nevertheless, the biogenesis, composition, and function of these
      intranuclear membrane cisternae are unknown. Membrane systems with a striking
      ultrastructural resemblance to the NCS, termed R-rings, are induced in nuclei of
      tissue culture cells by overexpression of the central repeat domain of the
      nucleolar protein Nopp140. Here we provide a first molecular characterization of
      the NCS and compare the biogenesis of these two enigmatic organelles. Like the R
      rings, the NCS consists of endoplasmic reticulum harboring the marker glucose-6
      phosphatase. R-ring formation initiates at the nuclear envelope, apparently by a
      calcium-mediated Nopp140-membrane interaction, as supported by the calcium
      binding ability of Nopp140, the inhibition of R-ring formation by calcium
      chelators, and the concentration of Nopp140 and complexed calcium in R-rings.
      Although biogenesis of the NCS may initiate similarly, the reduced presence of
      complexed calcium and Nopp140 suggests the involvement of additional factors.

PMID- 17429076
TI  - Loss of cell adhesion causes hydrocephalus in nonmuscle myosin II-B-ablated and
      mutated mice.
AB  - Ablation of nonmuscle myosin (NM) II-B in mice during embryonic development leads
      to marked enlargement of the cerebral ventricles and destruction of brain tissue,
      due to hydrocephalus. We have identified a transient mesh-like structure present
      at the apical border of cells lining the spinal canal of mice during development.
      This structure, which only contains the II-B isoform of NM, also contains beta
      catenin and N-cadherin, consistent with a role in cell adhesion. Ablation of NM
      II-B or replacement of NM II-B with decreased amounts of a mutant (R709C), motor
      impaired NM II-B in mice results in collapse of the mesh-like structure and loss
      of cell adhesion. This permits the underlying neuroepithelial cells to invade the
      spinal canal and obstruct cerebral spinal fluid flow. These defects in the CNS of
      NM II-B-ablated mice seem to be the cause of hydrocephalus. Interestingly, the
      mesh-like structure and patency of the spinal canal can be restored by increasing
      expression of the motor-impaired NM II-B, which also rescues hydrocephalus.
      However, the mutant isoform cannot completely rescue neuronal cell migration.
      These studies show that the scaffolding properties of NM II-B play an important
      role in cell adhesion, thereby preventing hydrocephalus during mouse brain
      development.

PMID- 17429078
TI  - Multiple interactions drive adaptor-mediated recruitment of the ubiquitin ligase
      rsp5 to membrane proteins in vivo and in vitro.
AB  - Recognition of membrane proteins by the Nedd4/Rsp5 ubiquitin ligase family is a
      critical step in their targeting to the multivesicular body pathway. Some
      substrates contain "PY" motifs (PPxY), which bind to WW domains in the ligase.
      Others lack PY motifs and instead rely on adaptors that recruit the ligase to
      them. To investigate the mechanism of adaptor-mediated ubiquitination, we have
      characterized the interactions between the adaptor Bsd2, the ubiquitin ligase
      Rsp5, and the membrane proteins Cps1, Tre1, and Smf1 from Saccharomyces
      cerevisiae. We have reconstituted adaptor-mediated modification of Cps1 and Tre1
      in vitro, and we show that two PY motifs in Bsd2 and two WW domains (WW2 and WW3)
      in Rsp5 are crucial for this. The binding of a weak noncanonical DMAPSY motif in
      Bsd2 to WW3 is an absolute requirement for Bsd2 adaptor function. We show that
      sorting of the manganese transporter Smf1, which requires both Bsd2 and Tre1,
      depends upon two PY motifs in Bsd2 and one motif in Tre1 but only two WW domains
      in Rsp5. We suggest that sequential assembly of first a Bsd2/Rsp5 complex, then a
      Tre1/Bsd2/Rsp5 complex followed by a rearrangement of PY-WW interactions is
      required for the ubiquitination of Smf1.

PMID- 17429077
TI  - Functional interaction between phosducin-like protein 2 and cytosolic chaperonin
      is essential for cytoskeletal protein function and cell cycle progression.
AB  - The Chaperonin Containing Tcp1 (CCT) maintains cellular protein folding
      homeostasis in the eukaryotic cytosol by assisting the biogenesis of many
      proteins, including actins, tubulins, and regulators of the cell cycle. Here, we
      demonstrate that the essential and conserved eukaryotic phosducin-like protein 2
      (PhLP2/PLP2) physically interacts with CCT and modulates its folding activity.
      Consistent with this functional interaction, temperature-sensitive alleles of
      Saccharomyces cerevisiae PLP2 exhibit cytoskeletal and cell cycle defects. We
      uncovered several high-copy suppressors of the plp2 alleles, all of which are
      associated with G1/S cell cycle progression but which do not appreciably affect
      cytoskeletal protein function or fully rescue the growth defects. Our data
      support a model in which Plp2p modulates the biogenesis of several CCT substrates
      relating to cell cycle and cytoskeletal function, which together contribute to
      the essential function of PLP2.

PMID- 17429079
TI  - Images in clinical medicine. Gravid uterus in an incisional hernia.

PMID- 17429080
TI  - Tobacco tightrope--balancing disease prevention and economic development in
      China.

PMID- 17429081
TI  - Making smoking history worldwide.

PMID- 17429082
TI  - Diabetes treatment--bridging the divide.

PMID- 17429083
TI  - Interleukin-1-receptor antagonist in type 2 diabetes mellitus.
AB  - BACKGROUND: The expression of interleukin-1-receptor antagonist is reduced in
      pancreatic islets of patients with type 2 diabetes mellitus, and high glucose
      concentrations induce the production of interleukin-1beta in human pancreatic
      beta cells, leading to impaired insulin secretion, decreased cell proliferation,
      and apoptosis. METHODS: In this double-blind, parallel-group trial involving 70
      patients with type 2 diabetes, we randomly assigned 34 patients to receive 100 mg
      of anakinra (a recombinant human interleukin-1-receptor antagonist)
      subcutaneously once daily for 13 weeks and 36 patients to receive placebo. At
      baseline and at 13 weeks, all patients underwent an oral glucose-tolerance test,
      followed by an intravenous bolus of 0.3 g of glucose per kilogram of body weight,
      0.5 mg of glucagon, and 5 g of arginine. In addition, 35 patients underwent a
      hyperinsulinemic-euglycemic clamp study. The primary end point was a change in
      the level of glycated hemoglobin, and secondary end points were changes in beta
      cell function, insulin sensitivity, and inflammatory markers. RESULTS: At 13
      weeks, in the anakinra group, the glycated hemoglobin level was 0.46 percentage
      point lower than in the placebo group (P=0.03); C-peptide secretion was enhanced
      (P=0.05), and there were reductions in the ratio of proinsulin to insulin
      (P=0.005) and in levels of interleukin-6 (P<0.001) and C-reactive protein
      (P=0.002). Insulin resistance, insulin-regulated gene expression in skeletal
      muscle, serum adipokine levels, and the body-mass index were similar in the two
      study groups. Symptomatic hypoglycemia was not observed, and there were no
      apparent drug-related serious adverse events. CONCLUSIONS: The blockade of
      interleukin-1 with anakinra improved glycemia and beta-cell secretory function
      and reduced markers of systemic inflammation. (ClinicalTrials.gov number,
      NCT00303394 [ClinicalTrials.gov].).

PMID- 17429084
TI  - Radiotherapy for glioblastoma in the elderly.
AB  - BACKGROUND: There is no community standard for the treatment of glioblastoma in
      patients 70 years of age or older. We conducted a randomized trial that compared
      radiotherapy and supportive care with supportive care alone in such patients.
      METHODS: Patients 70 years of age or older with a newly diagnosed anaplastic
      astrocytoma or glioblastoma and a Karnofsky performance score of 70 or higher
      were randomly assigned to receive supportive care only or supportive care plus
      radiotherapy (focal radiation in daily fractions of 1.8 Gy given 5 days per week,
      for a total dose of 50 Gy). The primary end point was overall survival; secondary
      end points were progression-free survival, tolerance of radiotherapy, health
      related quality of life, and cognition. RESULTS: We randomly assigned 85 patients
      from 10 centers to receive either radiotherapy and supportive care or supportive
      care alone. The trial was discontinued at the first interim analysis, which
      showed that with a preset boundary of efficacy, radiotherapy and supportive care
      were superior to supportive care alone. A final analysis was carried out for the
      81 patients with glioblastoma (median age, 73 years; range, 70 to 85). At a
      median follow-up of 21 weeks, the median survival for the 39 patients who
      received radiotherapy plus supportive care was 29.1 weeks, as compared with 16.9
      weeks for the 42 patients who received supportive care alone. The hazard ratio
      for death in the radiotherapy group was 0.47 (95% confidence interval, 0.29 to
      0.76; P=0.002). There were no severe adverse events related to radiotherapy. The
      results of quality-of-life and cognitive evaluations over time did not differ
      significantly between the treatment groups. CONCLUSIONS: Radiotherapy results in
      a modest improvement in survival, without reducing the quality of life or
      cognition, in elderly patients with glioblastoma. (ClinicalTrials.gov number,
      NCT00430911 [ClinicalTrials.gov].).

PMID- 17429085
TI  - Randomized, placebo-controlled trial of inactivated poliovirus vaccine in Cuba.
AB  - BACKGROUND: After poliomyelitis has been eradicated, access to live polioviruses
      will be highly restricted and the use of oral poliovirus vaccine (OPV) will
      probably be discontinued. Countries using OPV must decide whether to switch to
      inactivated poliovirus vaccine (IPV) or stop polio vaccination. Because data on
      the immunogenicity of IPV in tropical developing countries are limited, we
      conducted a randomized, controlled trial of IPV in Cuba. METHODS: The study
      population consisted of healthy infants born in Havana. A total of 166 infants
      were randomly assigned to two groups. Group A received a combination of the
      diphtheria-pertussis-tetanus (DPT) vaccine, the Haemophilus influenzae type b
      (Hib) vaccine, and IPV (DPT-Hib-IPV) at 6, 10, and 14 weeks of age. Group B, the
      control group, received a combination of the DPT vaccine and the Hib vaccine at
      6, 10, and 14 weeks of age. Another group (group C, 100 infants), which did not
      undergo randomization at the same time as groups A and B, received the DPT-Hib
      IPV combination at 8 and 16 weeks of age. Serum samples were collected before
      vaccination and at least 4 weeks after the last dose. Stool samples were obtained
      before and 7 days after challenge with OPV. RESULTS: The seroconversion rates in
      group A were 94%, 83%, and 100% for types 1, 2, and 3 poliovirus, respectively.
      There were no seroconversions in group B. The seroconversion rates in group C
      were 90%, 89%, and 90% for poliovirus types 1, 2, and 3, respectively. For groups
      A, B, and C, the virus isolation rates after challenge with OPV were 94%, 91%,
      and 97%, respectively, and the mean log10 viral titers of any serotype were 3.46,
      3.89, and 3.37, respectively. There was one major adverse event, an episode of
      hypotonia. CONCLUSIONS: Vaccination with two or three doses of IPV resulted in a
      rate of seroconversion of at least 90%, except for seroconversion against type 2.
      The viral titer of OPV shed in the stool after OPV challenge was reduced in both
      groups receiving IPV. (ClinicalTrials.gov number, NCT00260312
      [ClinicalTrials.gov].).

PMID- 17429086
TI  - Strategies for safer liver surgery and partial liver transplantation.

PMID- 17429087
TI  - Images in clinical medicine. Liver transplantation for polycystic liver disease.

PMID- 17429088
TI  - Case records of the Massachusetts General Hospital. Case 11-2007. A 59-year-old
      man with neck pain, weakness in the arms, and cranial-nerve palsies.

PMID- 17429089
TI  - Clinical trials in the elderly--a concept comes of age.

PMID- 17429090
TI  - Retinal progenitor cells--timing is everything.

PMID- 17429091
TI  - Sunitinib and hypothyroidism.

PMID- 17429092
TI  - Five-gene signature in non-small-cell lung cancer.

PMID- 17429093
TI  - Trial registration.

PMID- 17429094
TI  - Childhood progression of hereditary medullary thyroid cancer.

PMID- 17429095
TI  - Autoimmune pancreatitis.

PMID- 17429096
TI  - Primary percutaneous coronary intervention.

PMID- 17429097
TI  - Effects of dietary nitrate on blood pressure.

PMID- 17429098
TI  - Fatal reactivation of hepatitis B with temozolomide.

PMID- 17429099
TI  - Clinicopathologic correlations of stage IE/IIE primary thyroid diffuse large B
      cell lymphoma.
AB  - BACKGROUND: We studied the clinicopathological characteristics and prognoses of
      localized stage thyroid diffuse large B-cell lymphoma (DLBCL). PATIENTS AND
      METHODS: This study included 32 patients with stage I/IIE thyroid DLBCL. Their
      median age was 66 years, the male/female ratio was 10/22. RESULTS: As to the
      cellular immunophenotype, CD20 was positive in 31/32, CD5 in 0/32, CD10 in 4/32,
      CD23 in 1/32, BCL2 in 14/30, and BCL6 in 24/32. Twelve cases showed abnormal
      karyotypes: two cases with t(8;14)(q24;q32), four cases with 3q27, two cases with
      17p11, and four cases with other abnormal karyotypes. As for treatment, eight
      cases were treated with chemotherapy alone and 24 cases were treated with
      chemotherapy followed by radiotherapy. Complete response was achieved in 94%. The
      5-year progression-free survival was 84% and the 5-year overall survival was 90%
      with a median follow-up period of 62 months. The germinal center B-cell (GCB)
      type had a significantly better prognosis than the non-GCB type. CONCLUSION:
      Localized stage thyroid DLBCL is a disease with a relatively good prognosis. It
      is, however, a heterogeneous disease with regard to histological type and
      pathological state. Localized stage thyroid DLBCL has a good prognosis and it is
      that there are more GCB-type DLBCL lymphomas.

PMID- 17429100
TI  - Multicenter trial of neo-adjuvant chemotherapy followed by extrapleural
      pneumonectomy in malignant pleural mesothelioma.
AB  - BACKGROUND: The aim of this multicenter trial was to prospectively evaluate neo
      adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and
      radiotherapy, including quality of life as outcome. PATIENTS AND METHODS:
      Eligible patients had malignant pleural mesothelioma of all histological types,
      World Health Organization performance status of zero to two and clinical stage T1
      T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy
      consisted of three cycles of cisplatin and gemcitabine followed by EPP.
      Postoperative radiotherapy was considered for all patients. RESULTS: In all, 58
      of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five
      patients (74%) underwent EPP and in 37 patients (61%) the resection was complete.
      Postoperative radiotherapy was initiated in 36 patients. The median survival of
      all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45
      patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9).
      Psychological distress showed minor variations over time with distress above the
      cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N =
      26) at 3 months after surgery (P = 0.5). CONCLUSIONS: The observed rate of
      operability is promising. A median survival of 23 months for patients undergoing
      EPP compares favourably with the survival reported from single center studies of
      upfront surgery. This approach was not associated with an increase in
      psychological distress.

PMID- 17429101
TI  - Effects of a treatment gap during adjuvant chemotherapy in node-positive breast
      cancer: results of International Breast Cancer Study Group (IBCSG) Trials 13-93
      and 14-93.
AB  - BACKGROUND: The International Breast Cancer Study Group (IBCSG) conducted two
      complementary randomized trials to assess whether a treatment-free gap during
      adjuvant chemotherapy influenced outcome. PATIENTS AND METHODS: From 1993 to
      1999, IBCSG Trials 13-93 and 14-93 enrolled 2215 premenopausal and postmenopausal
      women with axillary node-positive, operable breast cancer. All patients received
      cyclophosphamide (Cytoxan, C) plus either doxorubicin (Adriamycin, A) or
      epirubicin (E) for four courses followed immediately (No Gap) or after a 16-week
      delay (Gap) by classical cyclophosphamide, methotrexate, and fluorouracil (CMF)
      for three courses. The median follow-up was 7.7 years. RESULTS: The Gap and No
      Gap groups had similar disease-free survival (DFS) and overall survival (OS). No
      identified subgroup showed a statistically significant difference, but
      exploratory subgroup analysis noted a trend towards decreased DFS for Gap
      compared with No Gap for women with estrogen receptor (ER)-negative tumors not
      receiving tamoxifen, especially evident during the first 2 years. CONCLUSIONS: A
      16-week gap between adjuvant AC/EC and CMF provided no benefit and may have
      increased early recurrence rates in patients with ER-negative tumors.

PMID- 17429102
TI  - Nerve conduction studies and current perception thresholds in workers assessed
      for hand-arm vibration syndrome.
AB  - BACKGROUND: Workers exposed to hand-arm vibration are at risk of developing the
      neurological abnormalities of hand-arm vibration syndrome (HAVS). The Stockholm
      classification of the neurological component of HAVS is based on history and
      physical examination. There is a need to determine the association between
      neurological tests and the Stockholm scale. AIMS: The main objective of this
      study was to compare the Stockholm neurological scale and the results of current
      perception threshold (CPT) tests and nerve conduction studies (NCS). METHODS:
      Detailed physical examinations were done on 162 subjects referred for HAVS
      assessment at a specialist occupational health clinic. All subjects had NCS and
      measurement of CPT. The Stockholm neurological classification was carried out
      blinded to the results of these neurological tests and compared to the test
      results. RESULTS: The nerve conduction results indicated that median and ulnar
      neuropathies proximal to the hand are common in workers being assessed for HAVS.
      Digital sensory neuropathy was found in only one worker. Neither the nerve
      conduction results nor the current perception results had a strong association
      with the Stockholm neurological scale. Exposure to vibration in total hours was
      the main variable associated with the Stockholm neurological scale [right hand:
      OR 1.30, 95% CI (1.10-1.54); left hand: OR 1.18, 95% CI (1.0-1.39)]. CONCLUSION:
      Workers being assessed for HAVS should have nerve conduction testing to detect
      neuropathies proximal to the hand. Quantitative sensory tests such as current
      perception measurement are insufficient for diagnostic purposes but may have a
      role in screening workers exposed to vibration.

PMID- 17429103
TI  - Penalized logistic regression for detecting gene interactions.
AB  - We propose using a variant of logistic regression (LR) with (L)_(2)
      regularization to fit gene-gene and gene-environment interaction models. Studies
      have shown that many common diseases are influenced by interaction of certain
      genes. LR models with quadratic penalization not only correctly characterizes the
      influential genes along with their interaction structures but also yields
      additional benefits in handling high-dimensional, discrete factors with a binary
      response. We illustrate the advantages of using an (L)_(2)-regularization scheme
      and compare its performance with that of "multifactor dimensionality reduction"
      and "FlexTree," 2 recent tools for identifying gene-gene interactions. Through
      simulated and real data sets, we demonstrate that our method outperforms other
      methods in the identification of the interaction structures as well as prediction
      accuracy. In addition, we validate the significance of the factors selected
      through bootstrap analyses.

PMID- 17429104
TI  - Fitting semiparametric random effects models to large data sets.
AB  - For large data sets, it can be difficult or impossible to fit models with random
      effects using standard algorithms due to memory limitations or high computational
      burdens. In addition, it would be advantageous to use the abundant information to
      relax assumptions, such as normality of random effects. Motivated by data from an
      epidemiologic study of childhood growth, we propose a 2-stage method for fitting
      semiparametric random effects models to longitudinal data with many subjects. In
      the first stage, we use a multivariate clustering method to identify G<<N groups
      of subjects whose data have no scientifically important differences, as defined
      by subject matter experts. Then, in stage 2, group-specific random effects are
      assumed to come from an unknown distribution, which is assigned a Dirichlet
      process prior, further clustering the groups from stage 1. We use our approach to
      model the effects of maternal smoking during pregnancy on growth in 17,518 girls.

PMID- 17429105
TI  - Bayesian regularization of diffusion tensor images.
AB  - Diffusion tensor imaging (DTI) is a powerful tool in the study of the course of
      nerve fiber bundles in the human brain. Using DTI, the local fiber orientation in
      each image voxel can be described by a diffusion tensor which is constructed from
      local measurements of diffusion coefficients along several directions. The
      measured diffusion coefficients and thereby the diffusion tensors are subject to
      noise, leading to possibly flawed representations of the 3-dimensional (3D) fiber
      bundles. In this paper, we develop a Bayesian procedure for regularizing the
      diffusion tensor field, fully utilizing the available 3D information of fiber
      orientation. The use of the procedure is exemplified on synthetic and in vivo
      data.

PMID- 17429107
TI  - Frozen shoulder: past, present, and future.

PMID- 17429106
TI  - Phospholipase C-beta 2 promotes mitosis and migration of human breast cancer
      derived cells.
AB  - Like most human neoplasm, breast cancer has aberrations in signal transduction
      elements that can lead to increased proliferative potential, apoptosis
      inhibition, tissue invasion and metastasis. Due to the high heterogeneity of this
      tumor, currently, no markers are clearly associated with the insurgence of breast
      cancer, as well as with its progression from in situ lesion to invasive
      carcinoma. We have recently demonstrated an altered expression of the beta2
      isoform of the phosphoinositide-dependent phospholipase C (PLC) in invasive
      breast tumors with different histopathological features. In primary breast tumor
      cells, elevated amounts of this protein are closely correlated with a poor
      prognosis of patients with mammary carcinoma, suggesting that PLC-beta2 may be
      involved in the development and worsening of the malignant phenotype. Here we
      demonstrate that PLC-beta2 may improve some malignant characteristics of tumor
      cells, like motility and invasion capability, but it fails to induce
      tumorigenesis in non-transformed breast-derived cells. We also report that,
      compared with the G(0)/G(1) phases of the cell cycle, the cells in S/G(2)/M
      phases show high PLC-beta2 expressions that reach the greatest levels during the
      late mitotic stages. In addition, even if unable to modify the proliferation rate
      and the expression of cell cycle-related enzymes of malignant cells, PLC-beta2
      may promote the G(2)/M progression, a critical event in cancer evolution. Since
      phosphoinositides, substrates of PLC, are involved in regulating cytoskeleton
      architecture, PLC-beta2 in breast tumor cells may mediate the modification of
      cell shape that characterizes cell division, motility and invasion. On the basis
      of these data, PLC-beta2 may constitute a molecular marker of breast tumor cells
      able to monitor the progression to invasive cancers and a target for novel
      therapeutic breast cancer strategies.

PMID- 17429108
TI  - Oldie but goldie: Bristow-Latarjet procedure for anterior shoulder instability.
AB  - PURPOSE: To analyse the functional and radiological outcomes of the Bristow
      Latarjet procedure in patients with recurrent anterior glenohumeral instability.
      METHODS: Records of 29 patients were reviewed retrospectively. Date of first
      dislocation, injury mechanism, and number of recurring dislocations before and
      after surgery were recorded. The overall function and stability of the shoulder
      was evaluated. RESULTS: 24 (83%) of the glenohumeral instabilities were caused by
      trauma. The mean number of recurring dislocations was 8 (95% confidence interval
      [CI], 0-18); one patient had had 40 recurrences. No dislocation ensued
      postoperatively. The overall functional outcome was good, with a mean Rowe score
      of 90 points (95% CI, 78-100). Scores of 17 (59%) of the patients were excellent,
      7 (24%) were good, 3 (10%) were fair, and 2 (7%) were poor. CONCLUSION: The
      Bristow-Latarjet procedure is a good surgical treatment for recurrent anterior
      inferior instability of the glenohumeral joint.

PMID- 17429109
TI  - Temporary coracoclavicular screw fixation for displaced distal clavicle
      fractures.
AB  - PURPOSE: To assess the treatment outcome of temporary coracoclavicular screw
      fixation for displaced distal clavicle fractures. METHODS: From January 1995 to
      December 2003, 30 consecutive patients with Neer type II displaced distal
      clavicle fractures were treated with open reduction and internal fixation using a
      coracoclavicular screw. The screw was removed under local anaesthesia after bony
      union. Patients were evaluated by clinical and radiological examination.
      Functional outcome was assessed by a simple shoulder test. RESULTS: There was
      100% union rate. All patients returned to their pre-injury activity level by 12
      months. One patient developed a superficial wound infection, which resolved with
      oral antibiotics. Two patients had problems with mild backing out of the screw,
      but both had bony union by the time of screw removal. The mean score of the
      simple shoulder test of 28 patients was 11. CONCLUSION: Treatment outcome using
      temporary coracoclavicular screw fixation for displaced distal clavicle fractures
      is favourable. The implant is readily available and the technique is simple,
      safe, cost-effective, and reproducible.

PMID- 17429110
TI  - Reproducibility of the Gartland classification for supracondylar humeral
      fractures in children.
AB  - PURPOSE: To evaluate the intra- and inter-observer reproducibility of the
      Gartland radiographic classification for supracondylar humeral fractures in
      children. METHODS: Anteroposterior and lateral radiographs of 50 supracondylar
      humeral fractures in children were graded on 2 separate occasions by 4
      orthopaedic surgeons according to the Wilkins modification of the Gartland
      classification. Data were analysed by calculating the Kappa values for intra- and
      inter-observer agreement to indicate the reproducibility of the classification.
      RESULTS: There was moderate inter-observer agreement, except for poor agreement
      over type I fractures. Type II fractures only showed fair to moderate agreement.
      Type III fractures and the flexion group showed good to very good agreement.
      Intra-observer agreement was good to very good. CONCLUSION: Surgeons should treat
      paediatric supracondylar humeral fractures based on an assessment of the degree
      of displacement rather than by employing the Gartland classification.

PMID- 17429111
TI  - Open reduction for late-presenting posterior dislocation of the elbow.
AB  - PURPOSE: To evaluate results of open reduction for late-presenting (more than 3
      weeks) posterior dislocation of the elbow in 10 patients. METHOD: Elbow stiffness
      was the main indication for surgery. The mean age of the patients was 34 (range,
      13-65) years; the mean time since injury was 4 (range, 2-6) months. All patients
      had non-functional elbow movement for any activity of daily living. Three
      patients had associated fractures around the elbow joint. RESULTS: At a mean
      follow-up of 19 (range, 11-28) months, 8 patients regained a functional range of
      movement for activities of daily living and maintained a median arc of flexion of
      100 degrees and a supination-pronation arc of 140 degrees. According to the Mayo
      Elbow Performance Index, the results of 5 patients were excellent, 3 were good,
      and 2 were poor. Complications included pin site infection (n=2), ulnar neuritis
      (n=1), and delayed wound healing (n=1). CONCLUSION: In patients with late
      presenting, unreduced elbow dislocation occurring up to 6 months earlier, open
      reduction is effective in restoring the joint to a painless, stable and
      functional state.

PMID- 17429113
TI  - Tensile strength of modified 4-strand cruciate technique for transversely or
      obliquely lacerated tendons.
AB  - PURPOSES: To assess the tensile strength of the modified 4-strand cruciate
      technique for obliquely lacerated tendons, and to compare the findings with the
      strength of transversely lacerated tendons repaired at various grasping depths.
      METHODS: 60 porcine front foot tendons were evenly divided into 4 groups. In
      groups 1 to 3, tendons were transversely lacerated and repaired with grasping
      points at both ends away from the laceration by 5 mm, 10 mm, and 15 mm
      respectively. In group 4, tendons were obliquely lacerated and repaired with a
      grasping point 5 mm away from the laceration on one end and 15 mm on the other.
      All tendons were repaired with a modified 4-strand core suture and continuous
      epitendinous suture, and then tested to failure in a tensile machine. RESULTS:
      The tensile strength in group 1 was significantly lower than that in the other 3
      groups (p<0.005). The tensile strength in group 4 was not significantly different
      from groups 2 and 3. CONCLUSION: The tensile strength of modified 4-strand
      cruciate repair configuration is not weakened in obliquely lacerated tendons; the
      grasping point at one end of the tendon being 15 mm away from laceration provides
      sufficient strength to compensate for the relatively weak 5-mm end. So long as
      one grasping point is away from the laceration site by 10 mm, the ultimate
      tensile strength of the transversely lacerated tendons appears acceptable. The
      modified 4-strand cruciate repair is safe to use for repairing obliquely
      lacerated tendons.

PMID- 17429112
TI  - Promotion of medial collateral ligament healing using a high-voltage electrical
      field.
AB  - PURPOSE: To assess the biomechanical and histological effects of a high-voltage
      electrical field on ligament healing. METHODS: 54 male Wistar rats were used. The
      medial collateral ligaments (MCLs) of 6 rats were measured for normal
      biomechanical failure load and stiffness. MCLs of the remaining 48 rats were
      transected and randomly assigned; half were subjected to a high-voltage
      electrical field for 8 hours a day (experimental group), and the other half were
      kept under normal conditions (control group). Eight rats from each group were
      killed 2, 4, and 6 weeks after the transection and their MCLs were tested
      biomechanically and histologically. RESULTS: Failure load and stiffness of the
      MCLs in the experimental group were significantly higher than those in the
      control group 2 weeks after transection, but not thereafter. At week 2, the
      granulation tissue completely occupied the space between the cut ends of the MCL
      in the experimental group, whereas some gaps remained in the control group.
      CONCLUSION: A high-voltage electrical field appear to accelerate ligament healing
      in the initial 2 weeks. Earlier initial healing may allow earlier start of the
      rehabilitation.

PMID- 17429114
TI  - Coronal bowing of the femur and tibia in Chinese: its incidence and effects on
      total knee arthroplasty planning.
AB  - PURPOSES: To study the incidence of femoral or tibial bowing in the coronal plane
      in a Chinese population, and how it affects the accuracy of bone cuts for total
      knee replacement when an intramedullary alignment system is used. METHODS:
      Standing radiographs of the entire lower limb of each patient with end-stage
      primary osteoarthritis of the knee were analysed. All radiographs were digitised
      and the extent of bowing in the coronal plane measured. A bowing was marked if an
      angulation was more than 2 degrees. The projected error of cutting was then
      calculated. RESULTS: Of 93 lower limbs, 58 (62%) of the femurs had marked bowing
      in the coronal plane; 41 (44%) had a mean lateral bowing of 5.3 (standard
      deviation [SD], 3.2) degrees; 17 (18%) had a mean medial bowing of 4.4 (SD, 1.9)
      degrees. Marked tibial bowing in the coronal plane was less common (30 tibias,
      32%). If a cutting error of more than 2 degrees was considered unacceptable,
      significantly more unacceptable cuts would ensue in the groups with marked bowing
      (p=0.003 for femurs and p<0.001 for tibia, respectively). CONCLUSION: The
      incidence of femoral or tibial bowing in the coronal plane was high in a Chinese
      population with end-stage osteoarthritis of the knee. This phenomenon may
      increase bone cut errors in total knee replacement if an intramedullary alignment
      system is used and the extent of bowing is not recognised.

PMID- 17429115
TI  - Traction and spica casting for closed femoral shaft fractures in children.
AB  - PURPOSE: To evaluate the treatment outcome of skin traction followed by spica
      casting for closed femoral shaft fractures in children. METHODS: Between
      September 1997 and December 2001 inclusive, outcomes of 63 children aged one
      month to 15 (mean, 5.3) years with closed femoral shaft fractures managed with
      skin traction and spica casting were reviewed. Depending on age, patients were
      kept in traction from 2 to 15 (median, 9) days, then in spica casts for 2 to 8
      (median, 5) weeks. RESULTS: Bony union took 3 to 12 (median, 6) weeks. There were
      no malunion, nonunion, or rotational deformities. Nor were there any significant
      limb length discrepancies, pressure sores, or nerve palsies. On no occasion was a
      spica cast removed and reapplied for loss of fracture reduction. At final follow
      up, limb length discrepancy was noted in 14 (22%) of the patients, but none had a
      discrepancy of greater than 1.5 cm or a short-legged gait. CONCLUSION: Skin
      traction followed by spica casting for closed femoral shaft fractures in children
      is safe, cost-effective and associated with a low complication rate. It is
      effective in children below 5 years of age and no less effective in older
      children, except in instances of open fracture, multiple fractures, or older
      children with large statures, which conditions render them intolerant to spica
      casts.

PMID- 17429116
TI  - Paediatric trauma epidemiology in an urban scenario in India.
AB  - PURPOSES: To identify the epidemiology of paediatric trauma in an urban scenario
      of India and compare results with studies from developed countries, and to
      formulate preventive measures to decrease such traumas. METHODS: Between January
      2004 and 2005 inclusive, 500 paediatric, orthopaedic trauma patients presenting
      to our hospital were prospectively studied. Information was recorded in a
      prescribed proforma. RESULTS: The children's ages ranged from 0 to 16 years; 274
      were males. Most fractures occurred in children aged 7 to 12 years and decreased
      in older children. The ratio of fractures in left versus right upper extremity
      was 2:1. In children aged 0 to 6 years, the most common injured site was the
      elbow, whereas in children aged 7 to 16 years it was the distal radius. In
      descending order, most injuries were sustained at home (47%), in school (21%),
      due to sports (17%), and due to vehicular accidents (13%). CONCLUSION: An
      effective accident prevention programme in developing countries requires changes
      in lifestyle and environment, and overcoming obstacles such as ignorance,
      illiteracy, and inadequate resources.

PMID- 17429117
TI  - Adductor strain and hip range of movement in male professional soccer players.
AB  - PURPOSE: To determine whether hip range of movement (ROM) can predict the
      occurrence of adductor strain among male professional soccer players. METHODS:
      120 subjects were prospectively selected from 6 professional soccer clubs in
      Australia. Internal rotation, external rotation, and ROM of the hip were measured
      using a goniometer before and during the course of a soccer season (2003-2004).
      When adductor strain occurred, further assessments of the hip were performed.
      Injured subjects' hip ROMs were measured again at the end of the season. RESULTS:
      Eight of the 120 subjects had 9 adductor strains (one bilateral). There was a
      correlation between preseason decreased hip ROM and occurrence of adductor
      strain. The mean preseason hip ROM was 44.7 degrees in the injured group and 53.7
      degrees in the uninjured group. Once the subjects were able to resume playing
      soccer, their hip ROM increased to near pre-injury levels. CONCLUSION: Decreased
      hip ROM may be considered an aetiological factor in the occurrence of adductor
      strain in male professional soccer players.

PMID- 17429118
TI  - Uncemented primary press-fit total hip arthroplasty: a 3 to 6 years of
      experience.
AB  - PURPOSE: To analyse the 3 to 6 years' clinicoradiological outcome of 45
      uncemented total hip arthroplasties performed in 37 patients using cementless
      Spotorno stem and St Nabor cup. METHODS: The main indications for surgery were
      avascular necrosis of the femoral head and rheumatoid arthritis. Younger patients
      with good bone quality and a trumpet-shaped femur were eligible. A single surgeon
      performed all the operations using a posterolateral approach. Patients were
      reviewed at 6 weeks, 3 months, 6 months, and yearly thereafter. The clinical
      status was recorded using the Harris Hip Score. All radiographs were analysed by
      2 independent blinded observers on 2 separate occasions. RESULTS: The mean follow
      up period was 49 months and the mean Harris Hip Score at the latest follow-up was
      94. Osseointegration in the form of trabeculae running from the endosteum to the
      prosthesis surface along with tropism of the calcar was evident in 73% of the
      hips. None of the remaining hips showed any continuous radio-opaque lines
      suggestive of a lack of bone ongrowth. Patients with endosteal condensation had
      better Harris Hip Scores. Intra-operative stability of the implants could fairly
      predict outcome. CONCLUSION: Initial clinicoradiological results of uncemented
      total hip arthroplasty are promising in younger patients with good bone quality
      and a trumpet-shaped femur.

PMID- 17429119
TI  - The efficacy of methotrexate-impregnated hydroxyapatite composites on human
      mammary carcinoma cells.
AB  - PURPOSE: To investigate the efficacy of local biodegradable composites of
      hydroxyapatite, plaster of Paris, and a binder of either alginate or chitosan
      impregnated with methotrexate on human mammary carcinoma cells. METHODS: An in
      vitro analysis of drug dissolution and a cytotoxicity test on human mammary
      carcinoma cells were performed over one month. Physicochemical properties of each
      composite were investigated using scanning electron microscopy, X-ray
      diffractometry, and Fourier transform infrared spectroscopy. RESULTS: Both
      composites with a binder of either alginate or chitosan could release
      methotrexate for over one month. The amount of methotrexate released depended on
      the amount of methotrexate loaded. The composite using alginate as a binder
      released a significantly greater amount of methotrexate than that using chitosan
      as a binder (p<0.05). The elution of both composites showed favourable
      cytotoxicity when the concentration was greater than 5 microg/ml. CONCLUSION:
      Methotrexate-impregnated hydroxyapatite composites appear to be effective local
      skeletal methotrexate delivery systems against human mammary carcinoma cells in
      an in vitro model.

PMID- 17429120
TI  - Publication bias in abstracts presented to the annual meeting of the American
      Academy of Orthopaedic Surgeons.
AB  - PURPOSE: To examine possible causes of publication bias in the orthopaedic
      literature so as to avoid inappropriate clinical decisions based on reviews of
      the literature. METHODS: Two reviewers independently reviewed abstracts presented
      to the 1999 American Academy of Orthopaedic Surgeons annual meeting. Data
      pertaining to sample size, statistical significance, study setting, country of
      origin, outcome, study type, and sponsorship were extracted from each abstract.
      The publication rate was measured after 5 years, by electronic searching and
      author contact. Predictors of publication were identified using logistic
      regression analysis. RESULTS: Of the 318 abstracts listed in the proceedings, 175
      (55%) were published within 5 years. Publication was associated with positive
      rather than neutral outcomes (odds ratio, 1.62; 95% confidence interval, 1.01
      2.59; p<0.05) and with the reporting of statistical significance (odds ratio,
      2.05; 95% confidence interval 1.24-3.39; p=0.005). Sponsorship, country of
      origin, sample size, study setting, and study type did not significantly
      influence the publication rate. CONCLUSION: Evidence of publication bias exists
      in abstracts presented at the 1999 American Academy of Orthopaedic Surgeons
      annual meeting. Clinical decisions based on the literature may be biased due to
      an over-representation of studies with positive outcomes.

PMID- 17429121
TI  - Computed tomographic evaluation of the odontoid process for two-screw fixation in
      type-II fracture: a Malaysian perspective.
AB  - PURPOSES: To measure the diameter of the odontoid process in a Malaysian
      population using computed tomographic (CT) scan and determine the feasibility of
      treating type-II odontoid fractures using 2 cortical screws. METHODS: CT images
      of the odontoid process of 85 patients aged 18 to 80 years were analysed; 69
      (81%) were male (mean age, 44 years) and 16 (19%) were female (mean age, 48
      years). Both anteroposterior (AP) and transverse diameters of the odontoid
      process were measured via axial CT images at 3 different levels: the base of the
      odontoid process and 1.2 mm and 2.4 mm above the base. RESULTS: The mean AP and
      transverse diameters of the odontoid process in men were 11.3 (range, 10.0-12.6;
      standard deviation [SD], 0.7) mm and 10.2 (range, 8.5-12.3; SD, 0.8) mm
      respectively, whereas in women were 10.9 (range, 9.4-13.2; SD, 0.8) mm and 10.1
      (range, 7.9-11.6; SD, 0.9) mm respectively. The difference in corresponding mean
      dimensions between men and women was not statistically significant. The mean AP
      diameter was significantly larger than the mean transverse diameter. At the base
      and 1.2 mm and 2.4 mm above the base, the respective transverse diameters of 4
      (5%), 13 (15%), and 24 (28%) of the patients were <9.0 mm. None had an odontoid
      AP diameter of <9.0 mm at any level. CONCLUSION: Two 3.5-mm cortical screws
      appear too big for fixation in one third of our sample presenting with type-II
      odontoid fracture. Fixation by two 2.7-mm screws is recommended for Malaysians
      and other Asian populations.

PMID- 17429122
TI  - Intra-operative Iso-C3D navigation for pedicle screw instrumentation of hangman's
      fracture: a case report.
AB  - Pedicle screw instrumentation of the upper cervical spine is rarely performed in
      trauma surgery because of the risk of damaging neurovascular structures. We
      report successful treatment of an unstable hangman's fracture with posterior
      pedicle screw fixation using Iso-C3D fluoroscopy-based computer navigation
      guidance. Postoperative computed tomographic images confirmed accurate placement
      of the pedicle screws. The navigation system is useful, especially in an unstable
      upper cervical spine injury where the likelihood of change in the inter-segmental
      relationship is maximal before and after positioning for surgery. The navigation
      system has the advantage of data acquisition after patient positioning, thus
      making safe pedicle fixation of the C1 and C2 vertebrae possible despite
      fractured posterior elements.

PMID- 17429123
TI  - Medial collateral ligament avulsion from both tibial and femoral attachments: a
      case report.
AB  - The medial collateral ligament (MCL) is the most commonly injured ligament of the
      knee joint. Proximal MCL tears occur more frequently than do distal ones. We
      report a 28-year-old man with a valgus injury of his left knee joint after a fall
      from a motorcycle. Magnetic resonance imaging of the affected knee joint revealed
      complete avulsion of the superficial MCL from both its femoral and tibial
      insertions. The meniscofemoral portion of the deep part of the MCL was also torn
      and the medial meniscus was subluxated. Such a pattern, an MCL tear with
      subluxation of the medial meniscus, is rare.

PMID- 17429124
TI  - Traumatic anterior knee dislocation and tibial shaft fracture: a case report.
AB  - We report a case of traumatic anterior dislocation of the left knee with an
      ipsilateral tibial shaft fracture in association with popliteal artery and common
      peroneal nerve injuries. To our knowledge, such a combination of injuries has not
      been reported before. All components of this injury were recognised and treated
      promptly with rehabilitation commencing early, resulting in a good functional
      outcome. We discuss the possible injury mechanism and management of this unusual
      case.

PMID- 17429125
TI  - Proximal femoral focal deficiency as a manifestation of Antley-Bixler syndrome: a
      case report.
AB  - We report a case of the Antley-Bixler syndrome in an 11-year-old girl. She
      presented with bilateral proximal femoral focal deficiency, right clubfoot, left
      radiohumeral synostosis, bilateral ear hypoplasia, cleft palate, tongue tie,
      missing teeth, congenital heart disease, a pelvic kidney with hydronephrosis, and
      mental retardation. Proximal femoral focal deficiency has never been reported
      before as a manifestation of Antley-Bixler syndrome. Her mother was exposed to
      radiation during an intravenous urogram done in the first trimester of pregnancy.
      Exposure to radiation has not been implicated as a cause of Antley-Bixler
      syndrome.

PMID- 17429126
TI  - Congenital pseudarthrosis of the clavicle: a case report.
AB  - Congenital pseudarthrosis of the clavicle is a rare entity of unknown aetiology.
      Its pathogenesis is related to the embryology of the clavicle. We present a 6
      year-old girl with congenital pseudarthrosis of the right clavicle. A prominence
      was noticed at birth between the middle and distal ends of the clavicle that
      increased in size when the right shoulder was actively mobilised. Radiographic
      examination revealed a hypertrophic pseudarthrosis of the clavicle. The
      pseudarthrosis was resected and the clavicular segments were fixed with an
      external fixator for 2 months until union. Clinical results were excellent at the
      7-year follow-up: the right shoulder was pain-free and the appearance
      satisfactory. Surgical treatment of congenital pseudarthrosis of the clavicle in
      children using an external fixator provides a better cosmetic outcome with
      smaller postoperative scars and avoids a second surgical procedure to remove the
      implants.

PMID- 17429127
TI  - Non-osseous extra-articular anterolateral talocalcaneal coalition: a case report.
AB  - We report a case of an extra-articular talocalcaneal coalition located
      anterolateral to the sinus tarsi. As non-osseous coalitions can be difficult to
      diagnose, physicians should keep this variant in mind in cases of a symptomatic
      hind foot with apparently equivocal radiological findings.

PMID- 17429128
TI  - Crystal arthropathy of the lumbar spine: a report of 4 cases.
AB  - Gout or pseudogout, caused by deposition of crystals, rarely affects the spine.
      We report 4 cases with gout or pseudogout in the lumbar spine. Two had cauda
      equina syndrome and another 2 had spinal stenosis. To avoid unnecessary surgery,
      this should be considered in the differential diagnosis when treating patients
      with histories of gout or pseudogout for spinal problems.

PMID- 17429129
TI  - Intra-osseous ganglion of the proximal humerus: a case report.
AB  - We report a 72-year-old woman with a type-1 intra-osseous ganglion in the
      proximal humerus, extending to the bone surface. We conducted a systemic review
      of intra-osseous ganglion cases in Japan to identify clinical features and
      pathogenesis of this condition. The anatomical distribution between intra-osseous
      ganglia without a communicating soft tissue ganglion (type 1) and those with
      (type 2) is different. The origins of intra-osseous ganglia vary and depend on
      their anatomical location. They can arise from within the bone or in the adjacent
      soft tissue, and can progress to a type-2 lesion in either an outside-in or
      inside-out fashion.

PMID- 17429130
TI  - Pigmented villonodular synovitis of the elbow in a 6-year-old girl: a case
      report.
AB  - Pigmented villonodular synovitis of the elbow is rare and even rarer in children.
      We report a case of pigmented villonodular synovitis of the elbow in a 6-year-old
      girl who underwent total synovectomy after the diagnosis was confirmed by biopsy.
      The osteochondral defect at the olecranon was filled with calcium phosphate bone
      paste. Two years after surgery, neither recurrence nor joint degeneration was
      found.

PMID- 17429131
TI  - Acquired radial club hand with humero-ulnar dislocation: a rare sequel to
      infantile compartment syndrome following venous cannulation: a case report.
AB  - Acquired radial club hand caused by infection has been reported occasionally. We
      report a rare case of acquired radial club hand with an associated septic
      dislocation of the elbow, primarily caused by compartment syndrome following
      venous cannulation. The deformity and instability were treated with distraction
      using an external fixator followed by a centralisation procedure. At the 2-year
      follow-up the appearance and functions of the left forearm had improved
      considerably and the wrist was stable. There was no deterioration in ulnar
      growth.

PMID- 17429132
TI  - Gluteal compartment syndrome following joint arthroplasty under epidural
      anaesthesia: a report of 4 cases.
AB  - Compartment syndrome is characterised by an increase in the interstitial pressure
      within a closed osseofascial compartment. This may be due to a decrease in
      compartment volume, an increase in compartment content or external pressures. We
      report 4 patients who required surgical decompression for gluteal compartment
      syndrome that developed after joint arthroplasty. Gluteal compartment syndrome is
      rare, has high morbidity, and can be life threatening if not detected early. We
      emphasise the importance of identifying patients at risk, frequent monitoring of
      patients with continuous epidural infusions, reporting of motor blockade, and
      regular changing of the patient's position postoperatively.

PMID- 17429133
TI  - A primary hydatid cyst of the gracilis: a case report.
AB  - Primary hydatid disease of the skeletal muscle without systemic involvement is
      rare. A 40-year-old woman presented with a painful mass in her medial left upper
      thigh. She was misdiagnosed as having a deep intramuscular abscess and a fine
      needle aspiration was performed, but the fluid came out crystal clear. Further
      inquiry revealed that her 16-year-old daughter had been operated on twice for
      liver and lung hydatid disease. Thus, a provisional diagnosis of hydatid disease
      was made. An echinococcal haemagglutination test was positive. Ultrasonography
      and magnetic resonance imaging findings were consistent with a type-2 hydatid
      cyst showing a 'water-lily' sign. The cystic mass within the left gracilis was
      resected en bloc. Adjunctive albendazole chemotherapy (400 mg/day) was prescribed
      for 3 months. At the 22-month follow-up, the patient remained free of symptoms.

PMID- 17429134
TI  - One-stage combined surgery with or without preoperative traction for
      developmental dislocation of the hip in older children.

PMID- 17429135
TI  - Locking compression plate in treatment of forearm fractures: a prospective study.

PMID- 17429136
TI  - Acute compression and lengthening by the Ilizarov technique for infected nonunion
      of the tibia with large bone defects.

PMID- 17429137
TI  - Aberrant regulation of messenger RNA 3'-untranslated region in human cancer.
AB  - The messenger RNA 3'-untranslated region (3'UTR) is emerging as critically
      important in regulating gene expression at posttranscriptional levels. The 3'UTR
      governs gene expression via orchestrated interactions between mRNA structural
      components (cis-elements) and specific trans-acting factors (RNA-binding proteins
      and non-coding RNAs). Alterations in any of these components can lead to disease.
      Here, we review the mutations in 3'UTR regulatory sequences as well as the
      aberrant levels, subcellular localization, and posttranslational modifications of
      trans-acting factors that can promote or enhance the malignant phenotype of
      cancer cells. A thorough understanding of these alterations and their impact upon
      3'UTR-directed posttranscriptional gene regulation will uncover promising new
      targets for therapeutic intervention.

PMID- 17429138
TI  - Pathology databanking and biobanking in The Netherlands, a central role for
      PALGA, the nationwide histopathology and cytopathology data network and archive.
AB  - Since 1991, a nationwide histopathology and cytopathology network and archive is
      in operation in The Netherlands under the name PALGA, encompassing all sixty-four
      pathology laboratories in The Netherlands. The overall system comprises
      decentralized systems at the participating laboratories, a central databank, and
      a dedicated communication and information exchange tool. Excerpts of all
      histopathology and cytopathology reports are generated automatically at the
      participating laboratories and transferred to the central databank. Both the
      decentralized systems and the central system perform checks on the quality and
      completeness of excerpts. Currently, about 42 million records on almost 10
      million patients are stored in the central databank. Each excerpt contains
      patient identifiers, including demographic data and the so-called PALGA
      diagnosis. The latter is structured along five classification axes: topography,
      morphology, function, procedure, and diseases. All data transfer and
      communication occurs electronically with encryption of patient and laboratory
      identifiers. All excerpts are continuously available to all participating
      pathology laboratories, thus contributing to the quality of daily patient care.
      In addition, external parties may obtain permission to use data from the PALGA
      system, either on an ongoing basis or on the basis of a specific permission.
      Annually, 40 to 60 applications for permission to use PALGA data are submitted.
      Among external users are the Dutch cancer registry, population-based screening
      programs for cancer of the uterine cervix and breast cancer in The Netherlands,
      and individual investigators addressing a range of research questions. Many
      scientific papers and theses incorporating PALGA data have been published
      already. In conclusion, the PALGA system is a unique system that requires a
      minimal effort on the part of the participating laboratories, while providing
      them a powerful tool in their daily practices.

PMID- 17429139
TI  - Comparing the prognostic value of PTEN and Akt expression with the Mitotic
      Activity Index in adjuvant chemotherapy-treated node-negative breast cancer
      patients aged <55 years.
AB  - BACKGROUND: The prognostic value of the PI3K/Akt/mTOR pathway and PTEN in
      invasive breast cancer (IBC) is controversial. Cell proliferation, especially the
      Mitotic Activity Index (MAI), is strongly prognostic in lymph node-negative
      (LNneg) invasive breast cancer. However, its prognostic value has not been
      compared with the value of Akt and PTEN expression. MATERIAL AND METHODS:
      Prognostic comparison of Her2Neu, p110alpha (PIK3CA), Akt, mTOR, PTEN, MAI and
      cell-cycle regulators in 125 LNneg patients aged <55 years with cyclophosphamide,
      methotrexate, and 5-fluorouracil (CMF)-based adjuvant systemic chemotherapy.
      RESULTS: Twenty-one (17%) patients developed distant metastases=DMs (median
      follow-up: 134 months). p110alpha correlated (p=0.01) with pAkt but only in PTEN
      negatives; pAkt correlated (p=0.02) with mTOR. PTEN-negativity correlated with
      high MAI, high grade and ER-negativity (p=0.009). The MAI was the strongest
      prognosticator (Hazard Ratio=HR=2.9, p=0.01). Her2Neu/p110alpha/Akt/mTOR features
      have no additional prognostic value to the MAI. PTEN had additional value but
      only in MAI<3 (39/125=31%; 8% DMs). 19/39=49% of the MAI<3 patients have combined
      MAI<3 / PTEN+ with 0% DMs, contrasting 15% DMs in MAI<3 / PTEN- (p=0.03).
      CONCLUSIONS: In T(1-3)N(0)M(0) adjuvant CMF-treated breast cancer patients aged
      <55 years, MAI was the strongest survival predictor. The PI3K/Akt/mTOR pathway
      and cell-cycle regulator characteristics had no additional prognostic value, but
      PTEN has. Patients with combined MAI<3 & PTEN-positivity had 100% survival. The
      small subgroup of MAI<3 patients that died were PTEN-negative.

PMID- 17429140
TI  - p16 is consistently expressed in endometrial tubal metaplasia.
AB  - BACKGROUND: Cell cycle proteins and HIF-1alpha with downstream factors are often
      abberrantly expressed in (pre)neoplastic tissue. METHODS: Paraffin-embedded
      specimens of inactive endometrium with TM (n=15), ovarian inclusion cysts (n=6),
      cervix with TM (tubal metaplasia) (n=3), Fallopian tubes (n=7), cycling
      endometrium (n=9) and a ciliated cell tumor of the ovary were stained for p16 and
      LhS28. 39 Endometrioid endometrial carcinomas and 5 serous endometrial carcinomas
      were stained for p16. Additionally, inactive endometrium (n=15) was
      immunohistochemically stained for p21, p27, p53, cyclin A, cyclin D1, cyclin E,
      HIF-1alpha, CAIX, Glut-1 and MIB-1. RESULTS: A mosaic pattern of expression of
      p16 was seen throughout in all cases of endometrial TM (15/15), in 2/6 of the
      ovarian inclusion cysts with TM, in all (3/3) cervical TM and focal in 5/7 of
      Fallopian tube cases. Mosaic expression was also seen in a ciliated cell tumor of
      the ovary and in 18/39 of endometrioid endometrial carcinomas, and diffuse p16
      expression was seen in 5/5 serous carcinomas. In comparison with normal
      endometrium, TM areas in the endometrium showed significantly increased
      expression of HIF-1alpha, cyclin E, p21 and cyclin A, and decreased expression of
      p27. Membranous expression of CAIX and Glut-1 was only seen in TM areas, pointing
      to functional HIF-1alpha. CONCLUSION: As p16 is consistently expressed in TM,
      less and only patchy expressed in the normal Fallopian tube, is paralleled by
      aberrant expression of cell cycle proteins, HIF-1alpha, CAIX and Glut-1 and
      resembles the pattern of p16 expression frequently seen in endometrial
      carcinomas, we propose endometrial TM to be a potential premalignant endometrial
      lesion.

PMID- 17429141
TI  - Chromatin phenotype karyometry can predict recurrence in papillary urothelial
      neoplasms of low malignant potential.
AB  - BACKGROUND: A preceding exploratory study (J. Clin. Pathol. 57(2004), 1201-1207)
      had shown that a karyometric assessment of nuclei from papillary urothelial
      neoplasms of low malignant potential (PUNLMP) revealed subtle differences in
      phenotype which correlated with recurrence of disease. AIM OF THE STUDY: To
      validate the results from the exploratory study on a larger sample size.
      MATERIALS: 93 karyometric features were analyzed on haematoxylin and eosin
      stained sections from 85 cases of PUNLMP. 45 cases were from patients who had a
      solitary PUNLMP lesion and were disease-free during a follow-up period of at
      least 8 years. The other 40 were from patients with a unifocal PUNLMP, with one
      or more recurrences in the follow-up. A combination of the previously defined
      classification functions together with a new P-index derived classification
      method was used in an attempt to classify cases and identify a biomarker of
      recurrence in PUNLMP lesions. RESULTS: Validation was pursued by a number of
      separate approaches. First, the exact procedure from the exploratory study was
      applied to the large validation set. Second, since the discriminant function 2 of
      the exploratory study had been based on a small sample size, a new discriminant
      function was derived. The case classification showed a correct classification of
      61% for non-recurrent and 74% for recurrent cases, respectively. Greater success
      was obtained by applying unsupervised learning technologies to take advantage of
      phenotypical composition (correct classification of 92%). This approach was
      validated by dividing the data into training and test sets with 2/3 of the cases
      assigned to the training sets, and 1/3 to the test sets, on a rotating basis, and
      validation of the classification rate was thus tested on three separate data sets
      by a leave-k-out process. The average correct classification was 92.8% (training
      set) and 84.6% (test set). CONCLUSIONS: Our validation study detected subvisual
      differences in chromatin organization state between non-recurrent and recurrent
      PUNLMP, thus allowing a very stable method of predicting recurrence of papillary
      urothelial neoplasms of low malignant potential by karyometry.

PMID- 17429142
TI  - CD31 and CD34 expression as immunohistochemical markers of endothelial
      transdifferentiation in human cutaneous melanoma.
AB  - INTRODUCTION: Vasculogenic mimicry, as previously described in aggressive
      melanoma, is characterized by the de novo generation of intratumoral patterned
      vascular channels, composed of PAS-positive basement membrane in the absence of
      endothelial cells, providing additional microcirculation, in support to the
      classic tumoral angiogenesis. METHODS: We investigated the immunohistochemical
      expression of two endothelial markers, CD31 and CD34, in tumoral cells of 60
      melanomas (45 primary cutaneous and 15 metastatic) as possible evidence of
      vasculogenic mimicry. In addition we investigated the relationship between CD31
      and CD34 expression and three pathological markers such as Clark's level, and
      skin ulceration, predictive of melanoma's aggressive behaviour, and mitotic
      index. RESULTS: No cases of common melanocytic nevi immunoreacted with CD31 or
      CD34. Random CD31 immunoreactivity was present in 6% of Clark's level I/II, 50%
      of Clark's level III and 80% Clark's level IV/V. CD34 was negative in Clark's
      level I/II but randomly stained the 20% and 55% of level III and IV/V
      respectively. 66% (10/15) of metastatic melanomas were CD31 positive showing a
      canalicular immunostaining pattern, conversely CD34 expression was never found.
      7/8 cutaneous ulcerated melanomas immunostained for CD31 and 4/8 for CD34. CD31
      immunostained 88% high/intermediate MI, and 53% of low MI melanomas. CD34
      decorated the 29% of high/intermediate and 38% of low MI melanomas. CONCLUSIONS:
      CD31 and CD34 immunoreactivity closely parallel both the different morphologic
      steps of melanocytic tumor progression and the presence of histological
      parameters related to the aggressive behaviour. Their expression could be related
      to endothelial transdifferentiation of melanoma cells although a consequent
      functional role has not been demonstrated yet.

PMID- 17429143
TI  - Orders of magnitude change in phenotype rate caused by mutation.

PMID- 17429145
TI  - Gain of chromosome 20q is an indicator of poor prognosis in colorectal cancer.

PMID- 17429146
TI  - An evaluation of traumatic and organizational experiences on the psychological
      health of New Zealand police recruits.
AB  - Police officers face the occupational hazard of repeated exposure to traumatic
      stressors. Additionally, as for employees of any large organization, they are
      subjected to routine organizational stressors in the workplace. Although police
      work is generally believed to be inherently stressful, very little is known of
      the impact of the police organization upon officers' psychological well-being.
      This study evaluated the impact on psychological health of both traumatic and
      organizational police experiences. Baseline measures of prior traumatic
      experiences, and psychological health were established at point of entry for 512
      police recruits. One year later, the impact of police related trauma and
      organizational events was assessed. Multiple regression analyses determined that
      while both traumatic events and organizational stressors affected psychological
      distress, organizational stressors had the strongest effect, including the
      exacerbation of Posttraumatic Stress Disorder symptoms. The main implication of
      these findings is that traumatic stress is a hazard for police officers, but the
      importance of daily organizational stressors must also be taken into account.

PMID- 17429147
TI  - Precarious employment experiences and their health consequences: towards a
      theoretical framework.
AB  - Fundamental shifts in the structure of labour markets, work systems, and
      employment relations of industrialized countries have outpaced changes in
      legislative, social and political mechanisms. As a result, a growing number of
      workers are exposed to precarious employment experiences, which we define as
      experiences that give rise to instability, lack of protection, insecurity, and
      social and economic vulnerability. These experiences represent a potentially
      significant occupational health risk. Our central objective is to develop a
      detailed framework that outlines the key aspects of work experiences that makes
      them precarious, and to consider links between these aspects and downstream
      health effects.

PMID- 17429148
TI  - Who is at risk for long-term sickness absence? A prospective cohort study of
      Danish employees.
AB  - AIM: The aim of this study was to identify who is at risk for long-term sickness
      absence according to occupation, gender, education, age, business sector, agency
      size and ownership. METHODS: The study is based on a sample of 5357 employees
      aged 18-69, interviewed in 2000. The cohort was followed up in a national
      register from January 1st 2001 to June 30th 2003, to identify cases with sickness
      absences that exceeded 8 weeks. RESULTS: During follow-up 486 persons (9.1%)
      experienced one or more periods of absence that exceeded 8 weeks. Higher risk of
      long-term sickness absence was associated with gender, age, educational level,
      and the municipal employment sector. Kindergarten teachers and people employed in
      day care, health care, janitorial work, food preparation, and unskilled workers
      were at greatest risk. Managers, computer professionals, technicians and
      designers, and professionals had lower risks. The health care and social service
      sectors were also in the high risk category, whereas the private administration
      sector had a lower risk. CONCLUSIONS: The study identifies specific occupational
      target populations and documents the need to perform job-specific research and
      tailor interventions if the intended policy of decreasing long-term sickness
      absence within the Danish labour market is to be realized.

PMID- 17429149
TI  - Undergraduate college students' upper extremity symptoms and functional
      limitations related to computer use: a replication study.
AB  - PURPOSE: To replicate Hupert et al.'s [5] evaluation of computer-related upper
      extremity musculoskeletal symptoms, functional limitations, academic performance
      impact, medication use and health services utilization among a college student
      population. SUBJECTS AND METHODS: A cross-sectional survey of undergraduate
      students living in a single residential dormitory at a private southwestern
      university who agreed to participate completed the College Computing & Health
      Survey in the Spring of 2001. RESULTS: Of the 127 dormitory residents, 116
      students participated and 54% reported experiencing symptoms associated with
      computer usage. Sixty-two percent of students surveyed experienced functional
      limitations. More women than men reported symptoms, functional limitations and
      neck and shoulder pain; those with functional limitations reported higher use of
      medications than other participants. CONCLUSION: These findings, which match the
      general findings of the previous research study conducted with the same
      instrument but in a different college student population, suggest a high level of
      computer-use-related musculoskeletal symptoms among college students.
      Universities may want to consider providing ergonomic training designed for
      college students to: conduct workstation assessments; identify computer related
      problems (risk factors); and, propose ergonomic solutions.

PMID- 17429150
TI  - Effects of a co-financed interdisciplinary collaboration model in primary health
      care on service utilisation among patients with musculoskeletal disorders.
AB  - BACKGROUND: In 1994 Sweden introduced a trial legislation allowing co-financing
      between authorities. The legislation aimed to stimulate new ways of collaboration
      between health and social care providers. One of the specific objectives was to
      make management of patients with conditions requiring multidisciplinary care more
      efficient and reduce costs. This study aims to assess if there were any
      differences in management of patients with musculoskeletal disorders at health
      centres applying the trial legislation compared to health centre with
      conventional care with regards to health services utilisation, health care
      interventions received, and costs. METHOD: A comparative prospective study was
      conducted. Consecutive patients aged 16-64 with musculoskeletal disorders
      attending the health care centres with (n=107) and without (n=31) co-financing
      model were interviewed at inclusion and after 6 and 12 months. Number of contacts
      with professionals and interventions received were registered. RESULTS: Patients
      at the intervention centres had significantly more contact with physiotherapists
      and physicians than the controls. Contacts with other services such as social
      insurance office, social services office or hospitals did not differ
      significantly between the groups. Costs were higher for the interventions
      centres. CONCLUSION: The findings do not suggest that the trial legislation
      reduced health care utilisation or costs for patients with musculoskeletal
      disorders.

PMID- 17429151
TI  - Interdisciplinary team discussion on work environment issues related to low back
      disability: a multiple case study.
AB  - From both a social and cost-benefit perspective, disability prevention and
      associated management strategies for assisting employees with back pain are only
      successful if they address critical return-to-work (RTW) determining factors
      present in the workplace, including ergonomic factors. Despite our current
      knowledge of the importance of an integrated team approach targeting these
      factors, questions remain regarding the conceptual framework adopted by
      contemporary rehabilitation teams as it relates to work-oriented interventions to
      accommodate employees back to work. The purpose of this study was to explore and
      describe the work environment issues discussed by an interdisciplinary team
      engaged in the work rehabilitation process of low back disability cases. A
      qualitative content analysis was conducted for 10 sample cases that underwent a
      rehabilitation program in Quebec (Canada). Drawing on the results of these
      analyses, a framework representing a synopsis of practitioners' involvement in
      the person-environment dynamic is presented and discussed. This study makes a
      unique contribution to the understanding of the 'real-life' content of an
      interdisciplinary activity in disability management, thus, helping rehabilitation
      practitioners to build knowledge on the practical application of a cross
      disciplinary framework to address work environment issues during the RTW process
      of those patients sick-listed due to back pain.

PMID- 17429152
TI  - Development of normative data for hand strength and anthropometric dimensions in
      a population of automotive workers.
AB  - OBJECTIVES: (1) To develop a normative data set for hand strength and
      anthropometric dimensions in automotive trim line workers. (2) To examine the
      relationship between trim line worker demographics and hand strength. BACKGROUND:
      Work tasks inherent in the automobile manufacturing industry such as forceful
      gripping and pinching, place physical demands upon the hands and fingers. This
      places workers at risk of developing a musculoskeletal injury. To reduce the risk
      of injury it is necessary to apply user strength data in the design phase of hand
      intensive tasks in order to create a fit between the person and the task. METHOD:
      Demographic variables, anthropometry and maximal grip and pinch strength were
      measured for one hundred and sixty-one trim line automotive workers. Their data
      were analyzed to examine the associations between the variables. RESULTS:
      Significant hand strength differences were found in relation to age, gender, hand
      dominance and anthropometry. The workers in this study had significantly lower
      strength values than previously used reference data. DISCUSSION: The disparity
      between the present study's strength data and that of Mathiowetz et al. [22] may
      be due to the different demographic pools from which the populations were drawn.
      A training effect appeared to exist in trim line workers which may have reduced
      the disparity in hand strength between the hands as the number of years worked on
      the line increased. CONCLUSION: Caution should be taken when applying
      international normative data sets to the design of hand tools/workstations, as
      global differences in hand strength are likely to exist.

PMID- 17429153
TI  - Stress in the workplace: a coaching approach.

PMID- 17429154
TI  - Clinical implications of pre-operative rapid BRAF analysis for papillary thyroid
      cancer.
AB  - The activating point mutation of the BRAF gene, BRAF(T1799A), is the most common
      and specific genetic alteration in adult papillary thyroid carcinoma (PTC) and a
      possible marker of malignant potential of PTC. We have applied the PCR-RFLP
      method using fine-needle aspiration biopsy samples not only to our clinical
      practice but also to the international medical assistance effort around the
      Semipalatinsk Nuclear Testing Site in Kazakhstan. Seventy-seven cases (100
      nodules) from Japan and 131 cases (137 nodules) from Kazakhstan were examined.
      There were 14 Japanese and 76 Kazakhstani cases of cytological malignant tumors
      from the examined samples. We detected 12 (85.7% of PTC) and 19 (25% of PTC)
      cases with BRAF(T1799A) among the Japanese and Kazakhstani cases, respectively.
      Of these cases, we found mutations in one cytologically "suspicious" case and
      even in two pathologically "benign" cases (after surgery in Kazakhstan). All of
      the BRAF mutation-positive cases, including those three, were confirmed as PTC by
      careful pathological examination, including immunohistochemical analysis. In
      summary, our PCR-RFLP method for BRAF(T1799A) detection using FNAB samples is
      useful not only for preoperative diagnosis of PTC but also as a complementary
      diagnostic tool for accurate pathological diagnosis, even after surgery.

PMID- 17429155
TI  - The ongoing debate in thyroid surgery: should frozen section analysis be omitted?
AB  - Controversies concerning the role of frozen section (FS) have been a matter of
      debate. The aim of this study was to identify the role of FS analysis in
      intraoperative decision making and analyze the effect of the cost in detecting
      thyroid malignancies in Turkey. Out of 214 consecutive patients who had been
      operated on for thyroid cancer between January 1996 and August 2004, 178 patients
      were evaluated retrospectively. All 178 patients were subjected to FS.
      Intraoperative FS correctly identified the pathology as malignant in 58.4% of
      patients. A true-positive FS result changed the surgical strategy in 30 (27.6%)
      cases False negative FS lesions were defined histologically as papillary
      microcarcinoma in 54%, follicular variant of papillary cancer in 18% and
      follicular cancer in 8% of cases. The sensitivities of FNAB and intraoperative FS
      in thyroid cancer patients were 22.5% and 58.4%, respectively. False negative FS
      results increased the cost for each informative FS from euro25 to euro42.7.
      Despite limitations, results of this study reject the idea that the role of FS is
      becoming limited. We recommend routine frozen section in the operative assessment
      of thyroid nodules. Omitting FS may be suggested only in cases with a FNAB
      revealing malignancy.

PMID- 17429156
TI  - Microbacterium terricolae sp. nov., isolated from soil in Japan.
AB  - The taxonomic positions of two novel strains isolated from a soil sample
      collected in Japan using Glucose-Peptone-Meat extract (GPM) agar plates
      supplemented with superoxide dismutase or superoxide dismutase plus catalase were
      investigated based on the results of chemotaxonomic, phenotypic and genotypic
      characteristics. Strains were Gram-positive, catalase-positive, non-motile
      bacteria with L-ornithine as a diagnostic diamino acid of the peptidoglycan. The
      acyl type of the peptidoglycan was N-glycolyl. The major menaquinones were MK-12
      and 13. Mycolic acids were not detected. The G+C content of the DNA was 70 mol%.
      Comparative 16S rRNA studies on the two isolated strains revealed that they
      belong to the genus Microbacterium. DNA-DNA relatedness data revealed that KV
      448(T) and KV-769 are a new species of the genus Microbacterium. From these
      results, we propose that these bacteria should be classified in the genus
      Microbacterium as Microbacterium terricolae sp. nov. The type strain of
      Microbacterium terricolae is KV-448(T) (=NRRL B-24468(T), NBRC 101801(T)).

PMID- 17429157
TI  - Identification of lactic acid bacteria from fermented tea leaves (miang) in
      Thailand and proposals of Lactobacillus thailandensis sp. nov., Lactobacillus
      camelliae sp. nov., and Pediococcus siamensis sp. nov.
AB  - Eighteen rod-shaped homofermentatives, six heterofermentatives, and a coccal
      homofermentative lactic acid bacteria were isolated from fermented tea leaves
      (miang) produced in the northern part of Thailand. The isolates were placed in a
      monophyletic cluster consisting of Lactobacillus and Pediococcus species. They
      were divided into seven groups by phenotypic and chemotaxonomic characteristics,
      DNA-DNA similarity, and 16S rRNA gene sequences. Groups I to VI belonged to
      Lactobacillus and Group VII to Pediococcus. All of the strains tested produced DL
      lactic acid but those in Group IV produced L-lactic acid. The strains tested in
      Groups I, II and V had meso-diaminopimelic acid in the cell wall. Six strains in
      Group I were identified as Lactobacillus pantheris; five strains in Group II as
      Lactobacillus pentosus; and four strains in Group V as Lactobacillus suebicus.
      Two strains in Group VI showed high DNA-DNA similarity for each other and MCH4-2
      was closest to Lactobacillus fermentum CECT 562(T) with 99.5% of 16S rRNA gene
      sequence similarity. Five strains in Group III are proposed as Lactobacillus
      thailandensis sp. nov., and MCH5-2(T) (BCC 21235(T)=JCM 13996(T)=NRIC 0671(T)=PCU
      272(T)) is the type strain which has 49 mol% G+C of DNA. Two strains in Group IV
      are proposed as Lactobacillus camelliae sp. nov., and the type strain is MCH3
      1(T) (BCC 21233(T)=JCM 13995(T)=NRIC 0672(T)=PCU 273(T)) which has 51.9 mol% G+C
      of DNA. One strain in Group VII is proposed as Pediococcus siamensis sp. nov.,
      and MCH3-2(T) (BCC 21234(T)=JCM 13997(T)=NRIC 0675(T)=PCU 274(T)) is the type
      strain which has 42 mol% G+C of DNA.

PMID- 17429158
TI  - Cloning and characterization of a new hetero-gene cluster of nonribosomal peptide
      synthetase and polyketide synthase from the cyanobacterium Microcystis aeruginosa
      K-139.
AB  - Two nonribosomal peptide synthetase genes responsible for the biosynthesis of
      microcystin and micropeptin in Microcystis aeruginosa K-139 have been identified.
      A new nonribosomal peptide synthetase gene, psm3, was identified in M. aeruginosa
      K-139. The gene is a cluster extending 30 kb and comprising 13 bidirectionally
      transcribed open reading frames arranged in two putative operons. psm3 encodes
      four adenylation proteins, one polyketide synthase, and several unique proteins,
      especially Psm3L consisting of halogenase, acyl-CoA binding protein-like protein,
      and acyl carrier protein. Alignment of the binding pocket of the adenylation
      domain and an ATP-PPi exchange analysis using a recombinant protein with the
      adenylation domain of Psm3B showed that Psm3G and Psm3B activate aspartic acid
      and tyrosine, respectively. Although disruption of psm3 did not reveal the
      product produced by Psm3, we identified microviridin B and aeruginosin K139 in
      the cells of M. aeruginosa K-139. The above-mentioned results indicated that M.
      aeruginosa possesses at least five nonribosomal peptide synthetase gene clusters.

PMID- 17429159
TI  - Two new species of the genus Micromonospora: Micromonospora chokoriensis sp. nov.
      and Micromonospora coxensis sp. nov., isolated from sandy soil.
AB  - Two actinomycete strains, 2-19(6)(T) and 2-30-b(28)(T), which produced single,
      non-motile noduler to warty spore surfaces, were isolated from sandy soil in
      Chokoria, Cox's Bazar, Bangladesh. A polyphasic study was carried out to
      establish the taxonomic position of these strains. Morphological and
      chemotaxonomic characteristics of these strains coincided with those of the genus
      Micromonospora. Phylogenetic analysis using 16S rDNA sequences indicated that
      these strains should be classified in the genus Micromonospora. The 16S rDNA
      sequence of strain 2-19(6)(T )showed closest similarity to the type strains of M.
      mirobrigensis (98.9%) and M. carbonacea (98.8%), and the strain 2-30-b(28)(T) to
      the type strains of M. purpureochromogenes (99.4%), M. halophytica (99.3%) and M.
      aurantiaca (99.2%). Furthermore, a combination of DNA-DNA hybridization results
      and some differential physiological and biochemical properties indicated that
      these strains were distinguished from the phylogenetically closest relatives.
      These strains therefore represent two novel species, for which the name
      Micromonospora chokoriensis sp. nov. and Micromonospora coxensis sp. nov. are
      proposed. The type strains are 2-19(6)(T) (=JCM 13247(T) =MTCC 8535(T)) and 2-30
      b(28)(T) (=JCM 13248(T)=MTCC 8093(T)).

PMID- 17429160
TI  - Luedemannella gen. nov., a new member of the family Micromonosporaceae and
      description of Luedemannella helvata sp. nov. and Luedemannella flava sp. nov.
AB  - Three actinomycete strains were isolated from soil samples collected in
      Bangladesh. The cultures formed spherical sporangia on short sporangiophores
      directly above the surface of the substrate mycelium. The sporangia developed
      singly or in clusters and each sporangium contained several nonmotile spherical
      to oval spores with a smooth surface. The strains 3-9(24)(T), 3-21(27) and 7
      40(26)(T) contained meso-diaminopimelic acid in the cell walls, predominant
      menaquinone MK-9(H(6)) and MK-9(H(4)) and glucose, xylose, galactose, mannose,
      rhamnose, ribose and arabinose in the whole-cell hydrolysates. Diagnostic
      phospholipid is phosphatidylethanolamine and branched anteiso-C(17 : 0) (30.0
      38.0%), anteiso-C(15 : 0) (12.5-14.0%), iso-C(16 : 0) (10.0-15.0%) and iso-C(15 :
      0) (10.0-12.0%) were detected as the major cellular fatty acids. The acyl type of
      the peptidoglycan was glycolyl and mycolic acids were not detected. The G+C
      content of the DNA was 71 mol%. The chemotaxonomic data indicate that these
      strains belong to the family Micromonosporaceae. Phylogenetic analysis based on
      16S rRNA gene sequence data suggested that the strains 3-9(24)(T), 3-21(27) and 7
      40(26)(T) fall within the family Micromonosporaceae. On the basis of phylogenetic
      analysis and characteristic patterns of signature nucleotides as well as
      morphological and chemotaxonomic data, Luedemannella gen. nov. is proposed for
      our 3 isolates. DNA-DNA hybridization experiment and phenotypic characterization
      indicated that the new genus was constituted of 2 species, as Luedemannella
      helvata sp. nov. for the strain 3-9(24)(T) (=JCM 13249(T)=MTCC 8091(T)) and
      Luedemannella flava for the strain 7-40(26)(T) (=JCM 13250(T)=MTCC 8095(T)) in
      the family Micromonosporaceae.

PMID- 17429161
TI  - New host-vector system in solvent-producing Clostridium
      saccharoperbutylacetonicum strain N1-4.

PMID- 17429162
TI  - Screening and identification of xylanase-producing bacteria from Thai soils.

PMID- 17429163
TI  - Distribution and characteristics of plasmid mobilizers in aquatic and soil
      environments and activated sludge.

PMID- 17429164
TI  - Supervisors' attitudes and skills for active listening with regard to working
      conditions and psychological stress reactions among subordinate workers.
AB  - We investigated whether supervisors' listening attitudes and skills were related
      to working conditions and psychological stress reactions among their
      subordinates. The subjects included 41 male supervisors and their immediate
      subordinates (n=203). The supervisors completed a short version of the Active
      Listening Attitude Scale (ALAS) consisting of two subscales: Listening Attitude
      and Listening Skill for Active Listening. The subordinates rated working
      conditions and their psychological stress reactions using selected scales of the
      Job Content Questionnaire and the Brief Job Stress Questionnaire. Those
      subordinates who worked under supervisors with a higher score of Listening
      Attitude and Listening Skill reported a more favorable psychological stress
      reaction than those who worked under supervisors with a lower score of Listening
      Attitude and Listening Skill. Those subordinates who worked under supervisors
      with a higher score of Listening Skill reported higher worksite support than
      those who worked under supervisors with a lower score of Listening Skill. Those
      subordinates who worked under supervisors with a higher score of Listening
      Attitude reported higher job control than those who worked under supervisors with
      a lower score of Listening Attitude. A supervisor's listening attitude and skill
      appeared to affect psychological stress reactions predominantly among male
      subordinates than among female subordinates. Psychological stress reactions were
      lower among younger subordinates who worked under supervisors with high listening
      skill, while no statistically difference was observed among older subordinates.
      These findings suggest that a supervisor's listening attitude and skill have an
      effect on working conditions and psychological stress reactions among
      subordinates and that the effects vary according to the subordinates' sex and
      age.

PMID- 17429165
TI  - Effect of particle size of intratracheally instilled crystalline silica on
      pulmonary inflammation.
AB  - Crystalline silica, known as a causal substance of silicosis, has been carefully
      evaluated for its carcinogenicity and fibrogenicity. In this study, we instilled
      crystalline silica of two different size (S(1.8) :1.80 microm (S.D. 2.0), S(0.7)
      :0.74 microm (S.D. 1.5)) into the trachea of rats to evaluate the size effects of
      the particles on pulmonary inflammation. S(1.8) and S(0.7) samples were
      administered to rats by a single intratracheal instillation (2 mg/ 0.4 ml
      saline). At three days, 1 wk and 1, 3 and 6 months after the instillation, the
      blood, bronchoalveolar lavage fluid (BALF), and pulmonary tissues were analyzed.
      Six images per HE-stained section were digitally captured and examined by the
      point counting method (PCM). Polymorphonuclear leukocyte (PMN)-in-blood specimens
      and cytospin specimens from BALF were stained immunohistochemically with BrdU. At
      six months after the instillation, the effects on inflammatory cells in the
      pulmonary tissues and BALF tended to be more marked in the rats instilled with
      S(1.8) than those instilled with S(0.7). Particularly, clear differences were
      observed in the number of inflammatory cells in BALF. Even if the particles are
      of the same chemical composition, the results suggest that, their biological
      effects vary depending on their particle size. Therefore, when such particles are
      used in workplaces, strict control systems should be established according to the
      risks present by different sizes of particles.

PMID- 17429166
TI  - Suppression of perfluoroisobutylene induced acute lung injury by pretreatment
      with pyrrolidine dithiocarbamate.
AB  - Perfluoroisobutylene (PFIB) is produced as a main by-product in large quantities
      by the fluoropolymer industry. As a highly toxic compound, even the case of brief
      inhalation of PFIB can result in acute lung injury (ALI), pulmonary edema and
      even death. To test for any preventive or therapeutic effects of pyrrolidine
      dithiocarbamate (PDTC), a NF-kappaB activation inhibitor, against PFIB inhalation
      induced ALI, mice were exposed in a flow-past exposure system to PFIB and the
      prophylactic and therapeutic effects of PDTC were studied. The inhibitory effects
      of PDTC on ALI, the activation of NF-kappaB, as well as the expression of
      cytokines (IL-1beta and IL-8) after PFIB exposure were evaluated. The results
      demonstrated that pretreatment with PDTC (120 mg/kg, 30 min before PFIB exposure)
      could significantly lower the lung coefficient (wet lung-to-body weight ratio,
      dry lung-to-body weight ratio, water content in the lung, and lung wet-to-dry
      weight ratio) and protein content in bronchoalveolar lavage fluid (BALF), but no
      effects of PDTC were found when PDTC was treated after PFIB inhalation,
      suggesting a preventative effect rather than a therapeutic effect of PDTC.
      Furthermore, the above preventative effects of PDTC (when given at 30 min before
      PFIB exposure) on PFIB-induced lung injury were achieved in a dose-dependent
      manner. In support of these preventive effects of PDTC, our toxicological studies
      demonstrated that PFIB-inhalation induced a quick activation of NF-kappaB (0.5 h
      post PFIB exposure) and expression of IL-1beta and IL-8 (0.5 h and 1 h post PFIB
      exposure, respectively). Pretreatment with PDTC (120 mg/kg, 30 min before PFIB
      exposure) resulted in a significant inhibitive effect on the activation of NF
      kappaB (0.5 h post PFIB exposure) and expression of IL-1beta and IL-8 (1 h post
      PFIB exposure). The mortality, the extent of lung injury of the mice indexed by
      lung coefficients, the content of total protein and albumin in BALF, as well as
      the lung histopathologic changes, were dramatically alleviated in PFIB exposure
      after pretreatment with PDTC, clearly suggesting that PDTC has a prophylactic
      role against PFIB inhalation-induced ALI, and that NF-kappaB activation might
      play a central role in initiating an acute inflammatory response and in causing
      injury to the lungs after PFIB inhalation.

PMID- 17429167
TI  - Unmetabolized VOCs in urine as biomarkers of low level exposure in indoor
      environments.
AB  - This study aimed to test the possible use of unmetabolized volatile organic
      compounds (VOCs) in urine as biomarkers of low-level indoor environmental
      exposure. Twenty-four subjects in 13 dwellings in a prefecture of Japan
      participated in this study. Air samples of the breathing zone were collected in
      the living room and bedroom, along with spot urine samples (before bedtime and
      first morning voids). Toluene, ethylbenzene, xylene isomers, styrene and p
      dichlorobenzene in the air and urine samples were measured by gas
      chromatography/mass spectrometry. For the 21 subjects without solvent exposure at
      work, there were significant correlations between the time-weighted average air
      concentrations in the bedroom and morning urinary concentrations for toluene, o
      xylene, total xylene and p-dichlorobenzene (correlation coefficients of 0.54,
      0.61, 0.56 and 0.84, respectively). Multiple linear regression analysis showed
      only air VOCs in the bedroom influenced the morning urinary VOC concentrations.
      We concluded that unmetabolized VOCs in the urine can provide a reliable
      biological indicator for air VOC exposures in non-occupational environments.

PMID- 17429168
TI  - Cognitive after-effects of vibration and noise exposure and the role of
      subjective noise sensitivity.
AB  - This study investigated the effects on attention performance after exposure to
      noise and whole-body vibration in relation to subjective noise sensitivity.
      Sixteen high and 16 low sensitivity male students, as determined by the Weinstein
      Noise Sensitivity Questionnaire, participated in a within-subjects experiment.
      Noise and vibration stimuli similar to those usually occurring in forestry
      vehicles were presented either individually, combined or not at all in four
      separate sessions lasting approximately 44 min. After exposure, participants
      completed an attention task and made subjective ratings of alertness. No main
      effect of noise sensitivity was observed in MANOVA, thus the data was pooled with
      the data from a pilot study using the exact same procedure without using a noise
      sensitivity inclusion criterion. The combined data revealed performance
      degradation in the attention task after exposure to vibration, regardless as to
      whether it was presented alone or in combination with noise. Increased ratings of
      alertness after vibration exposure and decreased ratings of alertness after noise
      exposure were also found. Neither synergistic nor antagonistic effects were
      observed from the combined noise and vibration exposure.

PMID- 17429169
TI  - Obstructive sleep apnea-hypopnea syndrome patients with overweight and
      hypertension in a Japanese workplace.
AB  - The objective of this study was to determine the relationship between obstructive
      sleep apnea-hypopnea syndrome (OSAHS) and overweight combined with hypertension
      and to examine whether OSAHS in conjunction with overweight and hypertension is
      associated with daytime sleepiness. In a Japanese workplace of 28,636 employees,
      368 men (19-62 yr old), who were anxious regarding their OSAHS symptoms,
      underwent home pulse oximetry. Of these, 153 men subsequently underwent all-night
      polysomnography (PSG), and OSAHS was diagnosed in 149. We next classified these
      149 men into the following groups: A [Overweight (-)/Hypertension (-), n=41], B
      [Overweight (-)/Hypertension (+), n=15], C [Overweight (+)/Hypertension (-),
      n=46], and D [Overweight (+)/Hypertension (+), n=47]. The Epworth Sleepiness
      Scale (ESS) was used to evaluate daytime sleepiness and the apnea-hypopnea index
      (AHI) was used to evaluate the severity of OSAHS. The averages of the ESS score
      and the AHI were compared in each group. Both the average ESS scores and the
      percentage of ESS scores > or =11 were not significantly different among the
      groups. The average AHI of group D was the highest among all of the groups and
      that of group C was significantly higher than those of groups A and B. In all the
      groups, the OSAHS patients with overweight and hypertension in this study had the
      highest AHI. The level of daytime sleepiness evaluated by the ESS in this study
      was almost the same in the OSAHS patients regardless of the degree of overweight
      or hypertension. These observations suggest that it is necessary to positively
      recommend PSG to men who are suspected of having OSAHS with overweight and
      hypertension, even if they do not have daytime sleepiness.

PMID- 17429170
TI  - Job stress and mental health of child-counseling office workers.
AB  - In Japan, consultations concerning child abuse cases are increasing rapidly, and
      the mental health of child-counseling office workers, who must deal with them,
      has emerged as an issue. To measure the state of mental health of these workers,
      and to clarify the characteristics of their job-related stress, we sent a
      questionnaire to 69 workers of child-counseling offices in Ibaraki Prefecture and
      obtained responses from 45. (1) Their job environment was characterized as high
      demand/low control/low reward. (2) The mean score of GHQ-12 of the subjects was
      5.9 +/- 3.6, indicating a very poor state of mental health. (3) Stress due to
      physical and verbal assaults by the parties involved in the cases and the
      psychological burden of intervention were found to be related to their poor
      mental health. Along with measures to prevent such assaults, training in
      intervention techniques, supervision, and care for psychological trauma are
      needed for child-counseling office workers.

PMID- 17429171
TI  - Lifestyle-determined gender and hierarchical differences in the lead
      contamination of bones from a feudal town of the Edo period.
AB  - We analyzed lead concentrations in bones from both genders of Japanese merchants
      (including rohnin; masterless samurai) and farmer classes, and compared the
      findings with those of the samurai class in the Edo period (1603-1867) to clarify
      gender and hierarchical (or occupational) differences in lead exposure during the
      Japanese feudal age. Merchant class females had significantly higher lead
      exposure (90.8 microg Pb/g dry bone; n=20) than males of the same class (39.9
      microg Pb/g dry bone; n=31) (p<0.01), indicating a remarkable gender difference
      in the urban population. In contrast to these high concentrations, males and
      females of the farmer class living in agricultural (or semi-rural) areas had
      significantly lower exposure (total mean value; 9.2 mug Pb/g dry bone; n=4) than
      both genders of the merchant class (p<0.001), and the gender difference was not
      significant in this class.

PMID- 17429172
TI  - Urinary 1-hydroxypyrene level relative to vehicle exhaust exposure mediated by
      metabolic enzyme polymorphisms.
AB  - Polycyclic aromatic hydrocarbons (PAH) are common air pollutants generated from
      incomplete combustion. The inhalation of exhaust fumes in urban areas has been
      suggested to be an additional contributing factor. This study investigated the
      influence of urban traffic exposure, personal lifestyle factors and metabolic
      enzyme polymorphisms on the urinary 1-hydroxypyrene (1-OHP) level, approximating
      exposure to PAH. With consents, 95 male taxi drivers exposed to vehicle exhaust
      in traffic and 75 male office employees received health interviews and provided
      urine samples. The results showed taxi drivers had higher urinary 1-OHP than the
      office employees (mean +/- standard deviation were 0.17 +/- 0.10 vs. 0.10 +/-
      0.07 mol/mol creatinine, p<0.001). The average urinary 1-OHP level increased from
      0.07 micromol/mol creatinine for non-smoking office employees to 0.17
      micromol/mol creatinine for those who smoked more than 20 cigarettes daily. The
      values for taxi drivers with similar smoking statuses were 0.12 and 0.25
      micromol/mol creatinine, respectively. Among non-smokers, taxi drivers still had
      higher 1-OHP level than office employees (0.12 +/- 0.05 vs. 0.07 +/- 0.03
      micromol/mol creatinine). The subjects with the m1/m2 or m2/m2 genotype of CYP1A1
      MspI or GSTM1 deficiency had significantly higher urinary 1-OHP levels than those
      with other CYP1A1 MspI and GSTM1 genotypes. Multivariate logistic regression
      analysis showed that taxi drivers (adjusted odds ratio (OR)=5.1, 95% confidence
      interval (CI)=1.1-13.6), smokers (OR=5.5, 95% CI=1.6-18.4) and subjects with the
      m1/m2 or m2/m2 genotype of CYP1A1 MspI (OR=9.7, 95% CI=2.7-35.0) had elevated
      urinary 1-OHP (greater than the overall median value, 0.11 micromol/mol
      creatinine). The results of this study suggest smoking contributes to the
      elevated urinary 1-OHP levels in taxi drivers in addition to taxi driving, and
      the excess level contributed from traffic exhaust and smoke was regulated by the
      CYP1A1 MspI genotype. Traffic exhaust exposure, smoking and CYP1A1 MspI genotype
      contributed to the variation in levels of urinary 1-OHP excretion.

PMID- 17429173
TI  - Workers' perception of the changes of work environment and its relation to the
      occurrence of work-related musculoskeletal disorders.

PMID- 17429174
TI  - Asthma caused by peracetic acid-hydrogen peroxide mixture.

PMID- 17429175
TI  - Analysis of urinary metabolites of polycyclic aromatic hydrocarbons in
      incineration workers.
AB  - Incineration workers are exposed to various pyrolysis products of organic
      materials, heavy metals and polycyclic aromatic hydrocarbons (PAHs). In this
      study, the exposure of incineration workers to PAHs was evaluated by measuring
      urinary metabolites of pyrene and naphthalene. The concentrations of urinary 1
      hydroxypyrene (1OHP), a metabolite of pyrene, and 2-naphthol (2NP), a metabolite
      of naphthalene, were measured among 100 workers in 4 different types of
      incinerators, both before and after their work shifts. These incinerators were
      two old types, one modern type and one outdoors. The medians of urinary 1OHP of
      before and after the work shifts obtained from all workers were 0.067 and 0.044
      mug/gCr, respectively; and the medians of urinary 2NP were 7.5 and 10.0 mug/gCr,
      respectively. A significant increase of 2NP after the work shift was found at one
      old incinerator. A significant decrease of metabolites was found at the other old
      incinerator. Significant correlations were found between urinary metabolites and
      cigarettes smoked per day. The effect of smoking on urinary metabolite levels was
      also important. Significant correlations were found between urinary 1OHP and 2NP
      levels in all workers. In multiple regression analysis smoking habit and
      incinerator type were found as significant factors. The improvement of the work
      environment, through decreasing exposure to both tobacco smoke and hazardous work
      shift-related substances, should be an occupational health aim.

PMID- 17429176
TI  - Physiologic root resorption in primary teeth: molecular and histological events.
AB  - Root resorption is a physiologic event for the primary teeth. It is still unclear
      whether odontoclasts, the cells which resorb the dental hard tissue, are
      different from the osteoclasts, the cells that resorb bone. Root resorption seems
      to be initiated and regulated by the stellate reticulum and the dental follicle
      of the underlying permanent tooth via the secretion of stimulatory molecules,
      i.e. cytokines and transcription factors. The primary root resorption process is
      regulated in a manner similar to bone remodeling, involving the same receptor
      ligand system known as RANK/RANKL (receptor activator of nuclear factor-kappa B/
      RANK Ligand). Primary teeth without a permanent successor eventually exfoliate as
      well, but our current understanding on the underlying mechanism is slim. The
      literature is also vague on how resorption of the pulp and periodontal ligament
      of the primary teeth occurs. Knowledge on the mechanisms involved in the
      physiologic root resorption process may enable us to delay or even inhibit
      exfoliation of primary teeth in those cases that the permanent successor teeth
      are not present and thus preservation of the primary teeth is desirable.

PMID- 17429177
TI  - Reproducibility of a hemi mandible positioning device and a method for measuring
      alveolar bone loss area in mice.
AB  - The objective of this study was to determine the reproducibility of a positioning
      device and a method for measuring the area of alveolar bone loss (ABL) in hemi
      mandibles of mice. Mucoperiosteal flaps were raised in CF1 Mus domesticus mice (n
      = 10) on the buccal aspects of the left side of the mandibles. Twenty-one days
      after surgery, the animals were sacrificed, and the mandibles were resected and
      stained with 1% toluidine blue. Two positioning devices, one for the buccal and
      the other for lingual aspect, were fabricated to keep the hemi mandibles in a
      standard position. The reliabilities of the positioning device and the method for
      measuring ABL area were analyzed using two series of pictures. The photographs
      were digitized and ABL measured as the exposed root area. Measurements were
      performed by two blinded examiners using image analysis software. Intra- and
      inter-examiner reproducibility of the positioning method ranged from -1.5 to
      +1.33 mm, while intra- and inter-examiner reproducibility of the measurement
      technique ranged from -3.37 to 14.70. Our results indicate that, due to the small
      variation observed in ABL area assessment, the positioning device and method for
      measuring ABL area represent useful techniques for evaluating ABL in mice.

PMID- 17429178
TI  - Effect of exposure time on curing efficiency of polymerizing units equipped with
      light-emitting diodes.
AB  - A study was conducted to evaluate the top and bottom hardness of two composites
      cured using polymerizing units equipped with light-emitting diodes [LED]
      (LEDemetron; Elipar FreeLight, Coltolux LED) and one quartz-tungsten halogen
      device [QTH] (Optilux 501) under different exposure times (20, 40 and 60 sec). A
      matrix mold 5 mm in diameter and 2 mm in depth was made to obtain five disc
      shaped specimens for each experimental group. The specimens were cured by one of
      the light-curing units (LCUs) for 20, 40 or 60 sec, and the hardness was measured
      with a Vickers hardness-measuring instrument (50 g/30 sec). Data were subjected
      to three-way ANOVA and Tukey's test (alpha = 0.05). LED LCUs were as effective as
      the QTH device for curing both composites. A significant increase in the
      microhardness values were observed for all light LCUs when the exposure time was
      changed from 20 sec to 40 sec. The Z250 composite showed hardness values that
      were usually higher than those of the Charisma composite under similar
      experimental conditions. LED LCUs are as efficient for curing composites as the
      QTH device as long as an exposure time of 40 sec or higher is employed. An
      exposure time of 40 sec is required to provide composites with a uniform and high
      Knoop hardness when LED light-curing units are employed.

PMID- 17429179
TI  - Depth of cure and hardness of an indirect composite polymerized with three
      laboratory curing units.
AB  - This study determined the hardness and curing depth of a light-activated indirect
      composite polymerized with three laboratory light-polymerizing units for the
      purpose of comparing the curing performance of the three units. A light-activated
      composite material for indirect application (Vita Zeta) was polymerized with
      three light-polymerizing units equipped with the following light sources: 1) one
      halogen lamp and two fluorescent lamps (alpha-Light II); 2) three halogen lamps
      (Twinkle HLG); and 3) one metal halide lamp (Twinkle LI). Knoop hardness and
      curing depth were determined for groups of five specimens using standardized
      testing methods. The results were compared using analysis of variance (ANOVA) and
      Scheffe's S intervals (alpha = 0.05). The Knoop hardness number (KHN) generated
      with the halogen-fluorescent unit (12.5 KHN) was significantly (P < 0.05) lower
      than those produced by the halogen unit (13.9 KHN) and the metal halide unit
      (14.2 KHN). Of the three units, the halogen-fluorescent unit exhibited the lowest
      depth of cure. Both the hardness and curing depth of the composite were
      influenced by the laboratory polymerizing units employed.

PMID- 17429180
TI  - Evaluation of long-term satisfaction with orthodontic treatment for skeletal
      class III individuals.
AB  - The aim of this study was to investigate the long-term satisfaction rate among
      skeletal class III patients following orthodontic treatment. Questionnaires were
      sent to 315 post-retention (between 5 to 22.5 years) patients who had received
      orthodontic treatment without any type of surgery for the correction of skeletal
      class III malocclusion. The questionnaire contained 28 questions: 10 regarding
      orthodontic treatment, 13 regarding satisfaction with orthodontic treatment
      outcomes, and five regarding psychosocial benefits of orthodontic treatment. The
      frequency of each variable was calculated and chi-squared test was used to
      determine gender correlations. The survey response rate was 15.8% (n = 40). Most
      patients were satisfied with their facial appearance (92.5%) and final esthetic
      profile (95%). Of the 5% who were dissatisfied with their final profiles,
      prognathic mandible was given as the reason. Most patients (90%) were satisfied
      with the overall treatment results. Moreover, patient perceptions of psychosocial
      benefits of treatment were mainly positive, with the majority (72.5%) stating
      their social communication had improved following orthodontic treatment. Chi
      squared test indicated almost no variations in response by gender. In conclusion,
      the majority of skeletal class III patients in the long-term post-retention
      period who had received orthodontic treatment were satisfied with the overall
      treatment outcome.

PMID- 17429181
TI  - In vitro antimicrobial activity of endodontic sealers, MTA-based cements and
      Portland cement.
AB  - The aim of this study was to evaluate the antimicrobial activity of different
      root-end filling materials - Sealer 26, Sealapex with zinc oxide, zinc oxide and
      eugenol, white and gray Portland cement, white and gray MTA-Angelus, and gray Pro
      Root MTA - against six different microorganism strains. The agar diffusion method
      was used. A base layer was made using Muller-Hinton agar (MH) and wells were
      formed by removing the agar. The materials were placed in the wells immediately
      after manipulation. The microorganisms used were: Micrococcus luteus (ATCC9341),
      Staphylococcus aureus (ATCC6538), Escherichia coli (ATCC10538), 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. Triphenyltetrazolium chloride 0.05%
      gel was added for optimization, and the zones of inhibition were measured. Data
      were subjected to the Kruskal-Wallis and Dunn tests at a 5% significance level.
      The results showed that all materials had antimicrobial activity against all the
      tested strains. Analysis of the efficacy of the materials against the microbial
      strains showed that Sealapex with zinc oxide, zinc oxide and eugenol and Sealer
      26 created larger inhibition halos than the MTA-based and Portland cements (P <
      0.05). On the basis of the methodology used, it may be concluded that all
      endodontic sealers, MTA-based and Portland cements evaluated in this study
      possess antimicrobial activity, particularly the endodontic sealers.

PMID- 17429182
TI  - A comparative SEM investigation of the smear layer following preparation of root
      canals using nickel titanium rotary and hand instruments.
AB  - The aim of this study was to compare the efficacy of NiTi flex K-file instruments
      and rotary FlexMaster and Race instruments (short for reamers with Alternating
      Cutting Edges) in root canal preparation. A total of 75 single rooted teeth with
      minimum curvature (< 5 degrees ) were selected and divided into three groups,
      each containing 25 teeth. Canals were prepared with NiTi flex K-file, FlexMaster
      and Race instruments using crown down preparation technique, up to size #40.
      After each instrument, the root canals were flushed with 5 ml of 0.5% NaOCl
      solution. The amount of debris and smear layer was quantified on the basis of
      Hulsmann method using a scanning electron microscope. Completely cleaned root
      canals were not found after instrumentation with any of the three instruments. In
      general, FlexMaster instruments left significantly less debris and smear layer
      than Race and NiTi flex K-file instruments (P < 0.05). NiTi flex K-files resulted
      in significantly more smear layer (P < 0.05) compared to Race and FlexMaster
      instruments only in the apical third of the canal.

PMID- 17429183
TI  - Health literacy education for children: acceptability of a school-based program
      in oral health.
AB  - A study was conducted to examine the acceptability and effectiveness of a new
      type of health literacy program for children. The program was organized in the
      form of a workshop by a dentist. Sixty-three students aged 11-12 years were
      divided into 14 groups. The discussion topic was the effectiveness of
      toothbrushing for preventing periodontal disease. To investigate this issue, each
      group was asked to choose the most appropriate study design for obtaining a
      reliable answer. After the group discussion, the participants received a lecture
      on appraising the quality of health information. Pre- and post-program
      questionnaire surveys were administered to assess the program. Sixteen percent of
      the students had searched for health information via the Internet; however, 56%
      claimed to be interested in searching for health information via the Internet.
      The most approved design was a cohort study (seven groups) as the most valid type
      of research for showing the effectiveness of toothbrushing. The post-program
      questionnaire survey revealed that 89% of participants easily understood the
      content of the program, and 76% found the program to be useful. These findings
      demonstrate the feasibility of using health literacy programs for schoolchildren.
      Health literacy programs for children will need to be developed and administered
      through collaboration between education and health professionals. (J. Oral Sci.
      49, 53-59, 2007).

PMID- 17429184
TI  - Diametral tensile strength and Vickers hardness of a composite after storage in
      different solutions.
AB  - This study evaluated the Vickers hardness (VHN) and diametral tensile strength
      (DTS) of the composite Z100 (3M ESPE) cured with: Quartz-Tungsten-Halogen light
      curing unit (QTH) (700mW/cm2- 40 s) and Argon laser (1,000mW/cm2- 10 s).
      Specimens of 2 mm depth and 8 mm diameter were immersed for 30 days at 37 degrees
      C in different storage means: water, alcohol, acetic acid, propionic acid and dry
      (control). The DTS (n = 8) was determined with a crosshead speed of 0.5 mm/min.
      The VHN (n = 8) test was carried out using a 50 g load for 60 s. Statistical
      analysis was performed by two-way ANOVA and Tukey's test (alpha = 0.05). The
      relationship between VHN and DTS was observed by Pearson correlation. The light
      source was not significant in both tests (VHN: P < 0.18; DTS: P < 0.92), but the
      factor storage showed significance (P < .001). Mechanical properties of the
      control group were statistically superior to those of the other storage groups
      (VHN = 102.2; DTS = 42.3 MPa). The alcohol group showed the lowest VHN (93.3) and
      DTS (33.8 MPa) values, which were similar to values for propionic (VHN = 97.5;
      DTS = 35.9 MPa) and acetic acids (VHN = 97.8; DTS = 36.1 MPa), but different from
      that of water (VHN = 102.2; DTS = 42.3 MPa). The relationship between VHN and DTS
      values presented a positive correlation (r2 = 0.90; P < 0.01).

PMID- 17429185
TI  - Effect of a xylitol and fluoride containing toothpaste on the remineralization of
      human enamel in vitro.
AB  - The aim of this study was to examine the effect of a fluoride and xylitol
      containing toothpaste on the remineralization of human enamel using Quantitative
      Light-induced Fluorescence (QLF). Human extracted teeth were cut longitudinally
      into three or four parts, and artificial subsurface lesion windows (2 mm x 3 mm)
      were created by immersion in demineralizing solution. Each enamel sample (n = 7)
      was treated for 3 min at 25 degrees C twice a day for consecutive 14 days with
      the slurry of a silica-based toothpaste 1) without F- and xylitol (blank), 2)
      with 500 ppm F- and 3) with 500 ppm F- and 5% xylitol toothpaste. In addition, we
      measured the remineralization ability of a commercially available toothpaste 4)
      with 500 ppm F-. The average fluorescence loss F (%) and lesion size (mm2) were
      determined with QLF. Another variable, delta Q, which was defined as the
      fluorescence loss integrated over the lesion size (%, mm2), was calculated. The
      results showed that the combination of 500 ppm F- and 5% xylitol toothpaste
      significantly (P < 0.05) recovered both the size and delta Q compared to the
      other groups. These findings suggested that inclusion of xylitol in fluoride
      toothpaste might be useful to enhance the remineralization in vivo.

PMID- 17429186
TI  - Forced eruption of adjoining maxillary premolars using a removable orthodontic
      appliance: a case report.
AB  - Forced eruption can be performed in teeth with caries, fracture, resorption or
      perforation in the cervical third of the root or isolated teeth with one- or two
      walled vertical periodontal defects. The purpose of this case report is to
      introduce an innovative orthodontic appliance which enables forced eruption. This
      appliance is easy to fabricate, cost-effective and very effective in forced
      eruption of non-restorable teeth.

PMID- 17429187
TI  - Apical surgery with calcium hydroxide capping of the exposed dentine: a case
      report.
AB  - Among a variety of biomaterials that have been reported to be ideal for dental
      repair, calcium hydroxide has been shown to have excellent long-term
      biocompatibility in the pulp and periapical areas. Here we report an alternative
      method employing calcium hydroxide for periapical surgery in a patient who
      developed internal apical resorption after traumatic injury, which negatively
      affected the quality of the cleaning, shaping and filling of the root canal.
      Obturation of the root canal as far as the middle third was followed by
      apicoectomy and ultrasonic retropreparation, and then retrograde root filling
      with resin cement sealer (Sealer 26) and zinc oxide powder. Calcium hydroxide
      paste was applied over the exposed dentinal surface, forming a barrier over the
      root apex. Radiographic follow-up after 24 months showed absence of apical
      resorption and complete periapical bone repair associated with a continuous
      apical lamina dura.

PMID- 17429188
TI  - Oral myiasis: a case report.
AB  - Oral myiasis is a rare disease in humans associated with poor oral hygiene,
      suppurative oral lesions, alcoholism and senility, among other conditions. A case
      of oral myiasis in a 34-year-old white male with advanced periodontal disease and
      neurologic deficit is reported. Treatment consisted of manual removal of the
      larvae, one by one, with the help of clinical forceps and subsequent management
      of the periodontal disease.

PMID- 17429189
TI  - [Bioaerosol concentrations and the identification of aerosolized bacteria by 16S
      rDNA analysis in work environments].
AB  - Bioaerosols cause sick building syndrome (SBS) and allergy. Many kinds of
      bioaerosol impactors are used for measurement of airborne microorganism
      concentrations in Japan. However, because the impactors are set on agar plates,
      some microorganisms cannot make colonies on the plates because of their lower
      viability or demands of nutrition. On the other hand, by double staining using
      ethidium bromide (EtBr) and carboxyfluorescein diacetate (CFDA), both total cells
      and cells with esterase activities can be detected without incubation. In this
      study, we calculated total cell concentrations and percentages of cells with
      esterase activities by the combination of filter sampling and double staining
      (EtBr and CFDA) from air of a laboratory, a conference room and outdoors.
      Temperature and humidity in the laboratory were constantly kept by an air
      conditioner, but in the conference room, an air conditioner was only operated
      sometimes because of its low frequency of use. There were no significant
      differences between total cell concentrations and humidity in both rooms, but
      increase of the percentages of cells with esterase activities depended on
      rainfall before the samplings (n=15, p<0.05 by Mann-Whitney test). The increase
      of active microorganisms by rainfall should be considered when we evaluate the
      risk of bioaerosols in the workplace. There were few differences in
      classifications of aerosolized bacteria by 16S rDNA sequence-based homology
      between the laboratory and the conference room. In both rooms, few pathogenic
      bacteria were observed.

PMID- 17429190
TI  - [Health impact assessment of "white-collar exemption" in Japan].
AB  - This work conducted a health impact assessment (HIA) of the Japanese Government's
      proposal concerning the introduction of so called "white-collar exemption" into
      the Japanese labor market. We adopted the Merseyside model and performed a rapid
      health impact assessment to assess the potential health effects of white-collar
      exemption. In this HIA, several health determinants which may possibly be
      affected, both positively and negatively, were identified based on experts'
      judgments. Literature evidence was assessed using PubMed and other databases. In
      addition, we searched for the opinions of those affected by white-collar
      exemption from internet web sites, and six concerns were identified. Long working
      hours were identified as the most serious concern by both experts and those
      affected. White-collar exemption may increase irregular working patterns which
      may be related to sleep disorder, stress, and cardiovascular disease. Family
      function and social participation will also be affected by irregular working
      patterns. On the other hand, in terms of stress, white-collar exemption may
      benefit from a higher degree of job control. There are possibilities that white
      collar exemption may enable an improved work-life balance and enable access of
      some groups of the population, such as people with disabilities or parents
      looking after children, greater access to the labour market. However, it is
      uncertain whether the benefits of white-collar exemption would overcome those of
      the current free-time or flex-time systems. The present work provides a wide
      range of health impacts of white-collar exemption, and will hopefully attract the
      attentions of decision-makers and those likely to be affected in order to
      contribute to policy-making.

PMID- 17429191
TI  - [Low back load and satisfaction rating of caregivers & care receivers in bathing
      assistance given in a nursing home for the elderly practicing individual care].
AB  - Since the public nursing care insurance system was enacted by the Japanese
      government, a transition from conventional group treatment to the individual care
      is required. In Japanese nursing homes for the elderly, bathing assistance
      methods have shifted from use of traditional mechanical bathtubs or a big bathtub
      to methods using small homestyle bathtubs, known as "individual bathing
      assistance". A study on the work load of caregivers with individual bathing
      assistance has never been conducted. Therefore, in a nursing home for the elderly
      practicing the individual bathing assistance method, we explored low back load
      using surface electromyography and trunk inclination angle measurement. Moreover,
      subjective evaluations by not only the caregivers but also the care receivers
      were investigated. The individual bathing assistance time per person was about 35
      min. When caregiver used the mechanical lift equipment to assist getting into and
      out of the bathtub, trunk inclination angle and muscle load were lower than with
      manual handling. Mechanical lift equipment had the advantage of reducing low back
      load. When caregivers gave assistance with dressing and ablution of the lower
      limbs, and in setting wheelchair footrests, trunk inclination angle and muscle
      load showed high values. The satisfaction rating of using the mechanical lift
      equipment showed the best score, and ratings of perceived exertion were about the
      same. Thus, the importance of safe and comfortable care for both caregivers and
      care receivers should be stressed to make effective use of assistance products
      and care equipment.

PMID- 17429192
TI  - [Status of mental health problems and care in Japanese business establishments].
AB  - In order to clarify the status of mental health problems and care in Japanese
      business establishments, a questionnaire was administered to occupational health
      staff in various enterprises (243 valid responses, 17.0%). The results reveal
      that, in most enterprises, there are workers suffering from stress-related
      disorders. Depression was most often seen (47.2%). Additionally, the results
      suggest that depression lead to long periods of time off. Therefore, measures
      against depression in employees are important. There were a lot of offices that
      executed mental health care by supervisors and managers or occupational health
      staff, or by educational training, or medical examination, etc. However, a clear
      statement of the plan concerning mental health care by employers had been
      executed by only about a half of employers. As the rate of patients or workers
      with long periods off work was not correlated to the care executed in the office,
      mental health care in its present status dose not seem to be effective.

PMID- 17429193
TI  - A rare cause of an endobronchial tumour in children: the role of interventional
      bronchoscopy in the diagnosis and treatment of tumours while preserving anatomy
      and lung function.
AB  - An 11-year-old girl was referred to our institution with complete obstruction of
      the left main stem bronchus by an endoluminal mass and was successfully treated
      by a combination of laser and mechanical debulking. Coring of the mass both
      allowed histological diagnosis (inflammatory myofibroblastic tumour) and
      definitive treatment with no recurrence after 3 years of follow-up. This case
      report emphasizes the major role of interventional bronchoscopy in the management
      of tumoural obstruction in children in whom benign conditions are frequent.
      Interventional bronchoscopy, which is minimally invasive when compared to
      surgery, in the vast majority of cases allows a precise diagnosis as it provides
      large samples of tissue removed during coring; in some cases it can be curative
      by itself and preserves lung parenchyma and function.

PMID- 17429194
TI  - Two cases of plasma cell leukemia with atypical immunophenotype.

PMID- 17429195
TI  - Telomere length shortening of peripheral blood mononuclear cells in solid-cancer
      patients undergoing standard-dose chemotherapy might be correlated with good
      treatment response and neutropenia severity.
AB  - This study evaluated the telomere length changes (DeltaTL) of peripheral blood
      mononuclear cells before and after repetitive standard-dose nonmyeloablative
      chemotherapy and the association of DeltaTL with treatment response and
      myelosuppression severity. TL was measured with Southern blot analysis in 32
      solid-cancer patients without bone marrow metastasis. The mean TL before
      chemotherapy (t0 TL) and after the 2nd (t1 TL), 4th (t2 TL) and 6th cycle (t3 TL)
      was 8.49, 8.33, 8.08 and 8.10 kb, respectively. TL became significantly decreased
      after 4 (p = 0.005) and 6 (p = 0.026) cycles of chemotherapy. The mean value of
      DeltaTL before and after completion of chemotherapy (t0 TL - t3 TL) was 0.46 kb.
      DeltaTL has a significant correlation with good treatment response (r = 0.448, p
      = 0.005) and the frequency of severe neutropenia (r = 0.417, p < 0.05).
      Consequently, TL of peripheral blood mononuclear cells was decreased by the
      repetitive nonmyeloablative standard-dose chemotherapy in solid-cancer patients
      without bone marrow metastasis, and DeltaTL was associated with good treatment
      response and neutropenia severity.

PMID- 17429196
TI  - Doxycycline: a pilot study to reduce diabetic proteinuria.
AB  - BACKGROUND: Activity of matrix metalloproteinases (MMPs), the enzymes primarily
      responsible for the deposition of extracellular matrix proteins, contributes to
      the pathogenesis of diabetic proteinuria. We evaluated the effect of doxycycline,
      a potent nonselective MMPs inhibitor, on reduction of proteinuria in diabetic
      patients. MATERIAL AND METHODS: In a self-control clinical trial, 35 patients
      with overt diabetic nephropathy (proteinuria >300 mg/24 h) received oral
      doxycycline 100 mg/day for 2 months. Twenty-four-hour urine volume, Cr and
      protein excretion were measured at baseline, after 1 and 2 months of treatment,
      and after 4 months of its discontinuation. Treatment-related side effects were
      closely monitored and documented. RESULTS: Mean (+/-SD) 24-hour urine protein was
      888 +/- 419 mg at baseline, 884 +/- 368 mg after 1 month, and 643 +/- 386 mg
      after the 2 months of doxycycline treatment. There was statistically significant
      reduction in proteinuria at 2 months of treatment vs. at the baseline (p <
      0.001). Mean 24-hour urine protein excretion increased to 1,021 +/- 422 mg 4
      months after doxycycline was discontinued. The changes in serum sodium,
      potassium, BUN and Cr concentrations, and blood pressure measurements during the
      2 months of treatment and follow-up period were not statistically significant.
      CONCLUSION: Proteinuria in patients with diabetic nephropathy can be reduced with
      low dose doxycycline therapy over a 2-month period of drug administration.
      Further studies are necessary to determine the long-term effect, the optimal
      dose, and the optimal duration of this potentially novel therapy.

PMID- 17429197
TI  - Long-term outcomes of cinacalcet and paricalcitol titration protocol for
      treatment of secondary hyperparathyroidism.
AB  - Long-term outcomes of combined cinacalcet and paricalcitol therapy for secondary
      hyperparathyroidism (SHPT) in patients failing traditional therapies with
      phosphate binders and active vitamin D compound analogs are not well described.
      We implemented a titration protocol for cinacalcet and paricalcitol and assessed
      its long-term effects on bone metabolism and disease in hemodialysis (HD)
      patients. Thirty-five patients were started on 30 mg of cinacalcet daily. After
      12 months, median cinacalcet dose was 60 mg. There was a 33% increase in number
      of patients receiving paricalcitol. Average corrected serum calcium (Ca)
      decreased from 9.5 to 8.8 mg/dl (p = 0.003, 95% CI 0.34-1.04); phosphorus (P)
      from 6.2 to 5.5 mg/dl (p = 0.047, 95% CI 0.01-1.34); Ca x P product from 58 to 48
      (p = 0.001, 95% CI 4.2-15.7); and intact PTH (iPTH) from 426 +/- 274 to 300 +/-
      228 pg/ml (p = 0.03, 95% CI 19.3-401.7). Number of patients achieving three or
      more K/DOQI criteria increased by 29% (p = 0.009).

PMID- 17429198
TI  - Effects of haemodialysis on circulating endothelial progenitor cell count.
AB  - During haemodialysis (HD) the endothelium is the first organ to sense and to be
      impaired by mechanical and immunological stimuli. We hypothesized that a single
      HD session induces mobilization of endothelial progenitor cells (EPCs) and that
      cardiovascular risk factors may influence this process. We quantified EPCs at
      different maturational stages (CD34+, CD133+/VEGFR2+) in blood samples from 30
      patients, during HD and on the interdialytic day, and in 10 healthy volunteers.
      Samples were drawn at the start of HD, 1, 2 and 3 h after, at the end of HD and
      at 24 h on the interdialytic day. Patients were divided into two groups based on
      a recent risk scoring system (SCORE project): low-risk (LR) and high-risk groups
      (HR). HD patients showed a significantly reduced basal number of EPCs with
      respect to healthy volunteers. In contrast, we observed increasing EPCs during HD
      whereas they diminished on the interdialytic day. The EPC number was directly
      correlated with HD time progression. The EPC number during HD was increased in
      the HR group with respect to the LR group. We had a direct correlation between
      risk score and number of EPCs. Cardiovascular risk factors influenced the
      mobilization of stem cells from the bone marrow. This feature could be the direct
      consequence of an augmented request of stem cells to respond to the most
      important endothelial impairment but could also show a defective capacity of EPCs
      to home in and repair the sites of vascular injury.

PMID- 17429199
TI  - Metabolic syndrome predicts hospitalization in hemodialysis patients: a
      prospective Asian cohort study.
AB  - BACKGROUND/AIMS: Metabolic syndrome (MS) increases morbidity and mortality in the
      general population. The effects of individual components of MS differ in
      hemodialysis (HD) patients, but the composite effects of MS in this population
      are unknown. METHODS: We performed a prospective, cohort study including 235 HD
      patients who were followed up for 3 years. We used modified Asian criteria of the
      National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)
      to define the presence of MS, and compared the hospitalizations and deaths in
      patients with and without MS. RESULTS: Patients with MS had a lower
      hospitalization-free ratio, greater annual hospitalization days and frequency
      than those without MS. The relative risk of the presence of MS was 1.669 in
      predicting first hospitalization for all causes. CONCLUSION: The modified Asian
      criteria for MS successfully predicted the risk of hospitalization as compared
      with NCEP ATP III criteria in HD patients.

PMID- 17429200
TI  - Extracellular water/intracellular water is a strong predictor of patient survival
      in incident peritoneal dialysis patients.
AB  - BACKGROUND: The mortality rate of peritoneal dialysis (PD) patients is still high
      and controversies persist regarding the mortality predictor. This study was
      designed to identify the predictability of the extracellular water/intracellular
      water ratio (E/I) on mortality in PD patients. METHODS: 227 incident PD patients
      were included. Time-dependent Cox proportional hazard regression was used to
      investigate the predictability of E/I on mortality. RESULTS: The 2- and 3-year
      survival was 74 and 65%, respectively. Univariate Cox proportional hazard
      regression analysis showed that the significant predictors of mortality were age,
      sex, Charlson Comorbidity Index, total Kt/V, serum albumin, pulse pressure,
      presence of malnutrition, and E/I. However, the final Cox proportional hazard
      models revealed that E/I was the only significant predictor. For every increase
      of 0.1 in the E/I value, the relative risk of death was 1.368. CONCLUSIONS: E/I
      is a strong independent predictor of mortality in incident PD patients.

PMID- 17429201
TI  - Impact of enteral supplements enriched with omega-3 fatty acids and/or omega-6
      fatty acids, arginine and ribonucleic acid compounds on leptin levels and
      nutritional status in active Crohn's disease treated with prednisolone.
AB  - BACKGROUND: Patients with Crohn's disease (CD) often develop malnutrition due to
      disease activity. We aimed to assess the effect of two different enteral
      supplements of Impact(R) Powder (IP; Novartis, Switzerland) on leptin levels and
      nutritional status in active CD patients during prednisolone treatment and
      tapering. METHODS: Thirty-one CD patients were randomized to IP Extra (group 1)
      or IP Standard (group 2). Leptin levels, nutritional, clinical and biochemical
      markers were studied at inclusion, after 5 and after 9 weeks of the study.
      RESULTS: Leptin levels, body mass index (BMI) and total cholesterol increased
      significantly within both groups at week 5 compared to inclusion. Leptin levels
      correlated with BMI in both groups at inclusion and in group 2 at week 9. In
      group 1, triglyceride levels remained unchanged, while levels in group 2
      increased significantly at week 5 compared to inclusion. Clinical and biochemical
      markers improved during the study compared to inclusion. CONCLUSIONS: Increased
      leptin levels during the study progress were transient, decreasing due to
      prednisolone withdrawal at the end of the study. Both formulas used as adjuvant
      therapy to prednisolone treatment were able to improve nutritional status in CD
      patients.

PMID- 17429202
TI  - Bouveret's syndrome: management and strategy of a rare cause of gastric outlet
      obstruction.

PMID- 17429203
TI  - Treatment of choledocholithiasis following Roux-en-Y hepaticojejunostomy using
      double-balloon endoscopy.

PMID- 17429205
TI  - Helicobacter pylori and gastric cancer: the causal relationship.
AB  - Gastric cancer has been recognized as an important cause of morbidity and
      mortality all over the world. Helicobacter pylori has been shown to have a causal
      relationship to gastric cancer. The knowledge into the mechanisms related to this
      has advanced considerably over the last few years thereby unarguably defining the
      role of this host-pathogen interaction. Epidemiological studies, research in
      animal models, molecular pathways involving host and bacterial factors,
      environmental factors and recent work on stem cells have contributed to
      understanding the origin and progress of this neoplasia. These form part of the
      myriad of interplaying factors resulting in the causal relationship.
      Nevertheless, current evidence is insufficient to accurately identify a
      definitive population where prevention or treatment strategies have to be
      targeted. Future trials will have to define the people at risk and shed more
      light in these areas.

PMID- 17429204
TI  - Fibrotic strictures and anti-TNF-alpha therapy in Crohn's disease.

PMID- 17429206
TI  - Antiplatelet therapy and the risk of bleeding induced by gastrointestinal
      endoscopic procedures. A systematic review of the literature and recommendations.
AB  - Antiplatelet drugs may increase the risk of bleeding induced by gastrointestinal
      endoscopic procedures. The antiplatelet effect of cyclooxygenase-1 inhibitors
      lasts less than 4 h. Skin and colonic bleeding times are prolonged for 3 and 5
      days after aspirin and ticlopidine withdrawal respectively. Major bleeding from
      endoscopic biopsies is extremely rare. In the four recent largest series, the
      general incidence of polypectomy-induced major bleeding was 0.11-0.42%. In more
      than half of the cases the bleeding was delayed, usually up to 2 weeks after the
      endoscopy. Although three retrospective studies suggested that aspirin does not
      increase the risk of polypectomy-induced bleeding, the power of these studies is
      limited. Similarly, it is difficult to draw conclusions from the two studies that
      assessed the risk of aspirin use during sphincterotomy. Aspirin withdrawal may be
      harmful in susceptible patients, mainly if it is for more than 7 days. There is
      no indication to stop aspirin before esophagogastroduodenoscopy, which may reveal
      aspirin-induced lesions. We recommend discontinuation of aspirin 4-7 days
      (according to the cardiovascular risk) before other endoscopic procedures. When
      aspirin is indicated for primary prevention, it can be resumed 14 and 10 days
      after polypectomy and sphincterotomy respectively. In cases of secondary
      prevention, it should be resumed after 1 week.

PMID- 17429207
TI  - Evaluating appropriateness of treatment for Crohn's disease: feasibility of an
      explicit approach.
AB  - BACKGROUND: Situations where practical therapeutic decisions differ from
      guidelines in the management of patients with Crohn's disease (CD) have been
      described through opinion surveys. The feasibility of actually documenting these
      situations using an explicit approach has not been examined. OBJECTIVE: The aim
      of this study was to evaluate the feasibility of a retrospective application of
      appropriateness criteria to a population of CD patients. METHODS: Medical records
      of a cohort of patients diagnosed with CD were systematically reviewed. We used
      appropriateness criteria for treatment of CD that had been developed by the
      European Panel on the Appropriateness of Crohn's Disease Therapy (EPACT). First
      we evaluated the level of precision of the elements abstracted from medical
      records needed in order to be able to apply these criteria. We then assessed the
      appropriateness of treatment for different CD categories. Only participants with
      at least one physician encounter during the preceding 6 months were included.
      RESULTS: 260 patient medical records were reviewed on site at 22
      gastroenterologists' offices over a 2-month period in 2005. 116 (44%) patients
      were excluded because they had not had at least one medical visit at their
      referred gastroenterologist during the preceding 6 months. Medical records for 8
      additional patients (3%) were not accessible. 136 (53%) medical records including
      148 encounters were available for analysis. Overall, elements necessary to
      determine the appropriateness of treatment were available in 94% (139/148) of
      encounters. These elements were available in more than 90% of cases for all CD
      categories except for mild-moderate luminal active CD where 66% were available.
      Among those with all necessary elements available, 18% of treatments were judged
      as appropriate, 29% inappropriate, 38% uncertain according to the EPACT criteria,
      and for the other 15%, appropriateness had not been rated by the EPACT panel.
      CONCLUSIONS: The information necessary to assess the appropriateness of treatment
      of major types of CD was generally both present and precise in medical records.
      Therefore, in addition to the intended prospective use of these criteria,
      retrospective evaluation of the appropriateness of CD treatment using medical
      records is also feasible with the EPACT criteria.

PMID- 17429208
TI  - Foraging habits of Alouatta palliata mexicana in three forest fragments.
AB  - The activity patterns and diet of howler monkeys (Alouatta palliata mexicana)
      were studied in 3 forest fragments in south-eastern Mexico: Playa Escondida
      (PLA), Agaltepec Island (AGA) and Arroyo Liza (LIZ). Intersite differences
      offered the opportunity to investigate the foraging adaptations of howler monkeys
      in response to population and habitat size. In the largest fragment (PLA), the
      howlers' diet was based on high-quality items (fruit and young leaves). In AGA,
      where the density of howlers was the highest, their diet was mostly folivorous
      with a marked exploitation of uncommon food items such as vines, lianas, shrubs
      and herbs. The dietary differences in AGA were accompanied by more time spent
      travelling and less time spent resting. Although LIZ was the smallest fragment
      and had a high howler density, the small group size and the use of energy
      minimizing strategies (less time spent travelling and more time spent resting)
      probably allowed howlers to maintain a frugivorous diet.

PMID- 17429209
TI  - Influence of social and environmental factors on nesting behaviour in captive
      gorillas (Gorilla gorilla gorilla).
AB  - Field studies on gorilla sleeping sites usually emphasize environmental
      influences on nest site selection, as individual nesting behaviours are usually
      not observed directly. In captivity, nesting behaviour and influencing factors
      are often overlooked. In the present study, the sleeping sites of members of a
      captive group of 16-21 gorillas were analysed, based on 152 nights over a 5-year
      period. Subadults tended to sleep apart from adults but clustered around the
      oldest blackback male. Full siblings and mothers with offspring were often
      nearest neighbours. Some sleeping dyads notably endured. Neither age of offspring
      nor rank of adult females influenced neighbour choice or distances; an interadult
      distance of 1.5-3 m was typical. Group dynamics were reflected in nesting
      arrangements. We suggest that possibilities for co-nesting and choice of sleeping
      sites should be provided to improve the welfare of captive gorillas and other
      great apes.

PMID- 17429210
TI  - Multimodal communication by male mantled howler monkeys (Alouatta palliata) in
      sexual contexts: a descriptive analysis.
AB  - We analyzed continuously sampled focal and ad libitum data of male mantled howler
      monkeys (Alouatta palliata) observed in random order. Males resided in two groups
      in a Costa Rican tropical dry forest environment (riparian habitat group: 3
      males, 15 females, 402 h observation; deciduous habitat group: 2 males, 8
      females, 114 h observation). Samples were limited to sexual contexts, in
      particular, the 60-min periods before and after each copulation observed within
      each group for each male. Time samples for each male were distributed equally
      before and after their own copulations. Before statistical analyses were
      conducted, data were corrected for differences in time sampled for males within
      each group. Four types of multimodal signaling were resolved: (1) audiovisual,
      (2) olfactory-visual, (3) olfactory-visual-tactile and (4) tactile-gustatory.
      Olfactory and tactile signals were never observed in combination with auditory
      signals. Consistent with expectation for a Neotropical, arboreal species,
      audiovisual signals were the most frequently observed type of multimodal
      communication in both groups (riparian habitat group: n = 139; deciduous habitat
      group: n = 66). Our evidence strongly suggests that unimodal signals may be
      combined and recombined to form complex, multimodal signals. Subordinate males in
      each group were more likely than dominant males to emit audiovisual signals
      before their own copulations. Male dyads were compared to assess the relative
      rate of audiovisual signaling by one male before another male's copulations. On
      average, the subordinate male of the riparian habitat group exhibited audiovisual
      signals at a higher rate before his own copulations compared to the rate of
      audiovisual signaling by his dominant challengers. The same comparisons are not
      significant for males in the deciduous habitat group. The pattern of male
      response that we report whereby subordinates emit some complex signals at a
      higher rate than dominants supports the 'terminal investment hypothesis'
      predicting that organisms should increase reproductive effort with age since, in
      mantled howlers, age correlates negatively with dominance rank. Additional,
      qualitative observations suggested that subordinates in both groups were most
      likely to obtain copulations when they increased rates of complex signaling
      and/or escalated interactions with their male challengers. Group differences were
      apparent, however, and we suggest factors that may account for these patterns. We
      assessed responses by female receivers of complex signals emitted by males in
      sexual contexts. In general, higher-ranking males are more attractive to females
      and are more successful at monopolizing them. Findings for other, less frequently
      displayed, multimodal signals (olfactory-visual, olfactory-visual-tactile and
      tactile-gustatory) are presented and discussed. We conclude with the suggestion
      that howlers may be a robust model for the investigation of complex signals in
      Neotropical primates, including research on functionally referential
      communication and context-dependent syntax.

PMID- 17429211
TI  - Can a group elicit duets from its neighbours? A field study on the black-crested
      gibbon (Nomascus concolor jingdongensis) in Central Yunnan, China.
AB  - We tested the intergroup spacing hypothesis with a 13-month field study of the
      interaction of singing behaviour between 3 neighbouring groups of black-crested
      gibbons (Nomascus concolor jingdongensis) at Mt. Wuliang, Central Yunnan, China.
      Neighbouring groups tended not to sing on the same day. While it did happen
      occasionally, a group seldom started a duet while its neighbour was singing, or
      within 5 min of the singing ceasing. The intersong intervals of 2 groups calling
      on the same day were similar or significantly longer than the intervals between
      any song bouts randomly selected from the same 2 groups when calling on different
      days. Groups did not sing in intergroup encounters and showed similar responses
      to neighbouring groups and groups with no common border. These results did not
      support the intergroup spacing hypothesis. The possible reasons are discussed.

PMID- 17429212
TI  - Negative blood culture infective endocarditis in the elderly: long-term follow
      up.
AB  - BACKGROUND AND AIM: Since the appearance of transesophageal echocardiography, the
      long-term prognosis of patients with negative blood culture infective
      endocarditis (NBCIE) has been found to be similar to that of patients with
      positive blood culture infective endocarditis (PBCIE). Nevertheless, the
      prognostic implications of NBCIE in the elderly (>65 years) has not, to date,
      been well documented. Our aim was to study the long-term prognosis of elderly
      patients with NBCIE and compare it with that of elderly patients with PBCIE.
      METHODS: Our study group was composed of 60 consecutive patients >65 years old
      with a diagnosis of IE (confirmed by vegetation analysis or following Duke's
      criteria). Every patient underwent transthoracic and transesophageal
      echocardiography. Fifty patients (83.3%) had PBCIE and 10 (16.7%) had NBCIE. All
      patients were followed up long-term, and the study end point was a composite one
      of death or need for valvular heart surgery. RESULTS: Mean age was 72.9 +/- 5
      years (56.7% male). Similar clinical and echocardiographic characteristics were
      found in both groups. Global mortality, need for surgery, predisposing factors
      and infection location were also similar in both groups. In addition, no
      differences were found in the long-term prognosis (log rank p = 0.29).
      CONCLUSIONS: In our series, the long-term prognosis in elderly patients with IE
      is independent of the presence of a negative or positive blood culture. Thus, age
      cannot be considered an independent risk factor of negative outcome in elderly
      patients with NBCIE.

PMID- 17429213
TI  - Adenovirus transmission in a nursing home: analysis of an epidemic outbreak of
      keratoconjunctivitis.
AB  - BACKGROUND: An epidemic outbreak of keratoconjunctivitis occurred in a nursing
      home in Madrid from August to December 2005. OBJECTIVE: This article reports the
      outbreak, the infection control measures taken, and risk factors for
      keratoconjunctivitis. METHODS: A cohort study was conducted on the nursing home
      staff and residents. Specific attack rates and relative risks with their 95%
      confidence intervals were estimated. A multivariate analysis (logistic
      regression) was performed proving odds ratios (OR) of becoming ill. Conjunctival
      swab samples were taken and tested for viral infection. More stringent infection
      control measures were implemented following the occurrence of the initial cases.
      RESULTS: Forty-six cases were identified in the nursing home (infection rates of
      30.5% in residents and 8.3% in workers). Total duration of the outbreak was 120
      days. Corneal ulcer occurred in 3 cases. The factors appearing as independent
      risk factors were age (OR = 5.7 in people aged >or=90 years compared to those
      aged <80 years), cognitive impairment (OR = 2.64) and nursing home floor (OR =
      2.74 for the first floor, where the outbreak started). Adenoviral DNA was
      amplified in 10 samples, and 8 of them could be typed as adenovirus serotype 8.
      CONCLUSIONS: Early adoption of adequate hygiene measures is essential to control
      these outbreaks. In nursing homes with a high number of people with cognitive
      impairment, an additional effort should be made when the first cases occur to
      provide such people an increased and improved care and monitoring.

PMID- 17429214
TI  - The neural crest: understanding stem cell function in development and disease.
AB  - Complex organs like the nervous system are composed of different cell types which
      are all derived from multipotent stem cells. In vertebrates, a transient
      population of stem cells, the neural crest, generates the entire peripheral
      nervous system as well as non-neural progeny. The developmental processes of
      cellular differentiation and proliferation require precise coordination and
      control. Errors in the programs that regulate stem cell function can lead to
      defects that manifest in developmental disorders, in some cases they might even
      induce cancer. It is therefore of fundamental interest to understand the
      mechanisms of stem cell maintenance and differentiation. Using the neural crest
      as a model system helps us not only to understand the role of stem cells in
      development but might also lead to new aspects for the cure of stem cell-related
      diseases.

PMID- 17429215
TI  - Amyloid-beta aggregation.
AB  - Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the
      growing population of elderly people. A hallmark of AD is the accumulation of
      plaques in the brain of AD patients. The plaques predominantly consist of
      aggregates of amyloid-beta (Abeta), a peptide of 39-42 amino acids generated in
      vivo by specific, proteolytic cleavage of the amyloid precursor protein. There is
      a growing body of evidence that Abeta aggregates are ordered oligomers and the
      cause rather than a product of AD. The analysis of the assembly pathway of Abeta
      in vitro and biochemical characterization of Abeta deposits isolated from AD
      brains indicate that Abeta oligomerization occurs via distinct intermediates,
      including oligomers of 3-50 Abeta monomers, annular oligomers, protofibrils,
      fibrils and plaques. Of these, the most toxic species appear to be small Abeta
      oligomers. This article reviews the current knowledge of the mechanism of Abeta
      assembly in vivo and in vitro, as well as the influence of inherited amino acid
      replacements in Abeta and experimental conditions on Abeta aggregation.
      Challenges regarding the reproducible handling of the Abeta peptide for in vitro
      assembly studies are discussed.

PMID- 17429216
TI  - Adenosine-based cell therapy approaches for pharmacoresistant epilepsies.
AB  - Despite recent medical advances pharmacoresistant epilepsy continues to be a
      major health problem. The knowledge of endogenous protective mechanisms of the
      brain may lead to the development of rational therapies tailored to a patient's
      needs. Adenosine has been identified as an endogenous neuromodulator with
      antiepileptic and neuroprotective properties. However, the therapeutic use of
      adenosine or its receptor agonists is largely precluded by strong peripheral and
      central side effects. Thus, local delivery of adenosine to a critical site of the
      brain may provide a solution for the therapeutic use of adenosine. The following
      rationale for the local augmentation of the adenosine system as a novel
      therapeutic principle in the treatment of epilepsy has been established: (1)
      Deficits in the adenosinergic system are associated with epileptogenesis and
      these deficits promote seizures. Thus, reconstitution of an inhibitory
      adenosinergic tone is a rational therapeutic approach. (2) The focal paracrine
      delivery of adenosine from encapsulated cells suppresses seizures in kindled rats
      without overt side effects. (3) The anticonvulsant activity of locally released
      adenosine is maintained in models of epilepsy which are resistant to major
      antiepileptic drugs. This review summarizes the rationale and recent approaches
      for adenosine-based cell therapies for pharmacoresistant epilepsies.

PMID- 17429217
TI  - Cortical plasticity: a view from nonhuman primates.
AB  - The primate's large brain-to-body weight ratio and high complexity are unusual in
      the animal kingdom. There is compelling evidence that it is an evolutionary
      adaptation that allows its owner to live a long life because of its competence in
      solving a wide range of problems. How primates use their brain to achieve such
      competence is of course of central interest to us. Here we review some key
      aspects of the neocortex that can be explored in nonhuman primates. Studies of
      the cortical circuits in the visual cortex reveal that the two major types of
      pathways, called feedforward and feedback, involve a very small fraction of the
      total synapses that any area contains. Nevertheless these pathways may be
      critical for some important forms of cortical plasticity, like perceptual
      learning and tasks involving perception and action.

PMID- 17429218
TI  - Bacterial meningitis: the role of transforming growth factor-Beta in innate
      immunity and secondary brain damage.
AB  - Project 6 of the NCCR 'Neural Plasticity and Repair' focuses on mechanisms of
      immunity and tissue damage in autoimmune and infectious diseases of the central
      nervous system (CNS). In one of the subprojects, the influence of transforming
      growth factor-beta (TGF-beta) on the immune reactivity of the CNS was
      investigated. In mice with Streptococcus pneumoniae-induced meningitis, a
      deletion of TGF-beta receptor II on leukocytes is found to enhance recruitment of
      neutrophils to the site of infection and to promote bacterial clearance. The
      improved host defense against S. pneumoniae was associated with an almost
      complete prevention of meningitis-induced vasculitis, a major intracranial
      complication leading to brain damage. The data show that endogenous TGF-beta
      suppresses host defense against bacterial infection in the CNS. This contrasts
      with findings from other body compartments that suggested that TGF-beta is a
      powerful chemotactic cytokine and increases microbial clearance.

PMID- 17429219
TI  - Repair of the injured spinal cord. A joint approach of basic and clinical
      research.
AB  - The myelin protein Nogo-A is a potent inhibitor of neurite outgrowth in the
      central nervous system, thus contributing to the incapacity of fiber tracts in
      the adult spinal cord to regenerate after injury. In this review we report on a
      joint approach of different research groups to develop a therapy applying anti
      Nogo-A antibodies to the injured spinal cord. While basic researchers took the
      initiative to provide means of neutralizing the inhibitory effect of Nogo-A and
      demonstrated enhanced fiber growth, regeneration and functional recovery both in
      rodent and primate models, clinical groups and rehabilitation engineers have
      sought to translate this novel strategy into a clinical setting.

PMID- 17429220
TI  - New technologies and concepts for rehabilitation in the acute phase of stroke: a
      collaborative matrix.
AB  - The process of developing a successful stroke rehabilitation methodology requires
      four key components: a good understanding of the pathophysiological mechanisms
      underlying this brain disease, clear neuroscientific hypotheses to guide therapy,
      adequate clinical assessments of its efficacy on multiple timescales, and a
      systematic approach to the application of modern technologies to assist in the
      everyday work of therapists. Achieving this goal requires collaboration between
      neuroscientists, technologists and clinicians to develop well-founded systems and
      clinical protocols that are able to provide quantitatively validated improvements
      in patient rehabilitation outcomes. In this article we present three new
      applications of complementary technologies developed in an interdisciplinary
      matrix for acute-phase upper limb stroke rehabilitation - functional electrical
      stimulation, arm robot-assisted therapy and virtual reality-based cognitive
      therapy. We also outline the neuroscientific basis of our approach, present our
      detailed clinical assessment protocol and provide preliminary results from
      patient testing of each of the three systems showing their viability for patient
      use.

PMID- 17429221
TI  - NK cell increase in neonates from the preterm to the full-term period of
      gestation.
AB  - BACKGROUND: Several studies have reported differences in lymphocyte phenotype in
      preterm and full-term neonates as compared to children and adults. However, a
      detailed description of the immunologic cell populations of neonates
      corresponding to the gestational age is needed. This will be helpful for clinical
      practice to find the best way to prevent neonatal infections or strengthen the
      immune system of newborns with some kind of immunodeficiency. OBJECTIVE: To study
      maturation of the immune system throughout gestation, describing the variations
      of the lymphocyte populations in function of the gestational week when born.
      METHODS: We performed a descriptive study in 134 healthy newborns (gestation age
      25-42 weeks), quantifying the relative and absolute counts of cell populations in
      umbilical cord blood obtained during delivery, by a four-color flow cytometry
      single platform. RESULTS: We first compared the very-preterm (25-30 weeks),
      preterm (31-36 weeks) and full-term (37-42 weeks) neonates. We found higher
      absolute counts of all cell populations in the full-term group and lower absolute
      and relative values of NK cells in the very-preterm group. After that, we
      analyzed the lymphocyte populations week to week (from week 31 to 41) and found
      the lowest values of T cells (CD4+ and CD8+) for week 36. However, lower
      percentages of CD4+ T cells and higher percentages of NK cells were observed in
      week 38 and 41. CONCLUSION: We found an increase in cord blood NK cells with
      gestational age, both in terms of absolute counts and of percentage values.
      Moreover, the %NK cells showed a pattern opposite to %CD4+ T cells along the
      studied period.

PMID- 17429223
TI  - The use and abuse of antibiotics.

PMID- 17429222
TI  - Myocardial adaptation to anemia and red blood cell transfusion in premature
      infants requiring ventilation support in the 1st postnatal week.
AB  - BACKGROUND: Although transfusion practice in very premature infants is becoming
      more restrictive, little is known about myocardial adaptation to anemia during
      the 1st postnatal week. OBJECTIVES: To determine the central hemodynamic effects
      of anemia and red blood cell transfusion in very preterm infants undergoing
      intensive care. METHODS: Twenty-nine neonates of less than 30 weeks gestational
      age were treated for respiratory distress syndrome, following a strict protocol.
      Echocardiographies were performed at the 4th and 6th postnatal days, which
      corresponded to, respectively, just before and 48 h after an erythrocyte
      transfusion of 15 ml/kg in the 12 anemic infants. RESULTS: Anemic infants had
      increased stroke volume [2.1 (1.8-2.3) vs. 1.5 (1.3-1.6) ml/kg] and left
      ventricular (LV) output [312 (271-345) vs. 206 (177-240) ml/min/kg]. The
      relationship of the heart rate-corrected velocity of circumferential fiber
      shortening to LV end-systolic meridional wall stress indicated a higher
      contractile state in the anemic infants, with a higher y-intercept (p = 0.03) and
      a steeper slope (p = 0.05) of the regression line than in the nonanemic patients.
      Posttransfusion, the stroke volume, LV output, shortening fraction, and
      contractile state decreased to the values observed in the nonanemic infants.
      CONCLUSIONS: Myocardial contractility was a major component of the circulatory
      adjustments in the anemic premature infants requiring ventilation support in the
      early neonatal period. Changes in LV performance associated with anemia were
      reversed by transfusion with no detrimental effect on right ventricular function,
      LV preload or the respiratory status of these patients.

PMID- 17429224
TI  - Prescribing for asthma in the outpatient clinics in Riyadh: Does it follow the
      guidelines?
AB  - In order to reduce the significant morbidity and mortality associated with
      asthma, current guidelines recommend the use of anti-inflammatory therapy in a
      step-wise approach. To obtain information on how physicians are treating asthma,
      we evaluated prospectively 243 newly seen asthmatics in the outpatient clinics in
      four hospitals in Riyadh. The patients were assessed by five pulmonologists who
      confirmed the diagnosis, established the severity, recorded the medications
      patients were taking, and the specialty of the prescribing physician. The inhaler
      technique was checked and changes made in the treatment were also recorded. The
      medications prescribed were ss agonists (inhaled 69%, oral 25%0, steroids
      (inhaled 33%, systemic 8%), cough mixtures (30%), antibiotics (26%), theophylline
      (21%), and miscellaneous 16%. Over half of the patients (55%) were taking ss
      agonists regularly. The most frequent changes made were as follows: adding
      steroids (inhaled 56%, systemic 27%, or increasing the inhaled dose 16%),
      starting inhaled ss agonists (28%) and discontinuining theophylline (9%). The GPs
      were the group least inclined to prescribe inhaled steroids (P < 0.0001). The
      inhaler technique was poor in 53% of the patients. We conclude that in treating
      asthma, physicians are still relying more on bronchodilator and symptomatic
      therapy rather than anti-inflammatory therapy. There is also evidence to suggest
      overuse of antibiotics. Wide dissemination of the guidelines may alter the
      prescribing habits, and as many asthamtics are managed by GPs, this group in
      particular should be targeted.

PMID- 17429225
TI  - Normal levels of the natural anticoagulants (proteins C & S and antithrombin III)
      and the fibrinolytic factors (tPA and PAI) in Arab children.
AB  - The diagnosis of many hemostatic defects in infancy and childhood depends on the
      establishment of normal levels of various hemostatic factors. In this study,
      measurements of the natural anticoagulants (proteins C, S, and antithrombin III),
      as well as the fibrinolytic factors (tPA and PAI) were undertaken in healthy
      neonates (cord blood; n = 56), as well as in healthy children, up to 12 years of
      age (n = 103). The results were compared to normal adult values obtained from
      blood donors (n = 49). Neonatal values were found to be 50% of those obtained in
      adults and their mean concentrations were as follows: ATIII antigen = 48.4%,
      ATIII activity = 61.6%, protein C antigen = 47.7%, protein C activity = 57.2%,
      total protein S = 41.8% and tPA = 1.9 ng/mL. PAI level (25.7 ng/mL) was similar
      to adult values. In the first three years of life, almost all the hemostatic
      factors, other than PAI, gained adults levels. The diminished concentrations of
      the natural anticoagulants, in addition to the hypofibrinolysis in neonates,
      shifts the hemostatic balance towards fibrin formation and safeguards effective
      hemostasis. The values obtained in this study may serve as local reference
      values.

PMID- 17429226
TI  - Myocardial bridges: Their clinical implications and prognostic signs.
AB  - Among 980 consecutive selective coronary angiograms performed, nine patients had
      myocardial bridges of the left anterior descending (LAD) coronary artery. The
      overall prevalence of myocardial bridges was 0.92%. Among these patients, three
      patients had coronary artery disease, while six cases were isolated myocardial
      muscle bridges. With respect to functional abnormality, three had grade III
      milking effect, three had grade II and three had grade I milking effect. The
      indications for coronary angiograms were typical chest pain in seven cases and
      atypical pain in two cases. Their clinical and laboratory investigations are
      presented with literature review.

PMID- 17429227
TI  - Ulex Europeus Agglutinin (UEA-I) lectin binding in breast carcinoma and its
      relationship to prognostic factors.
AB  - In this study, lectin binding was compared with pathological prognostic factors
      and clinical follow-up details. Formalin-fixed, paraffin-embedded tissues from 43
      cases of breast carcinoma were studied for binding with Ulex Europeus Agglutinin
      (UEA-I) lectin. Staining results were compared with tumor size, histologic and
      nuclear grade, lymph node status (number, capsular and pericapsular invasion),
      blood and lymphatic vessel invasion, ER and PR status, clinical stage and the
      patients' short-term follow-up details. Analysis of staining with UEA-I showed a
      significant relationship with blood vessel invasion (P < 0.01) and lymphatic
      vessel invasion (P < 0.05). Furthermore, PR showed a significant inverse
      correlation with lectin binding (P < 0.05). Staining with UEA-I related
      significantly with axilliary lymph node metastases (P < 0.05). UEA-I was positive
      in four (66.6%) out of six cases with distant organ mestastasis. This study
      confirms that, in breast cancer, lectin binding to the cancer cells can be a
      reliable indicator for axilliary metastases, and the need for additional
      therapeutic interventions.

PMID- 17429228
TI  - Renal tumors in adult Saudi patients: A review of 43 cases.
AB  - Seventy-nine patients with renal tumors were seen at King Khalid University
      Hospital (KKUH) over a 10-year period from 1985 through November 1995. In a
      retrospective study, we analyzed the records of 43 Saudi patients from all over
      the Kingdom; they represented 54% of all patients encountered. Fourteen percent
      of the patients had benign renal tumors in the form of angiomyolipoma and
      oncocytoma. Eighty-six percent of the patients had malignant renal tumors.

PMID- 17429229
TI  - Meeting the iron needs of infants and young chidren.

PMID- 17429230
TI  - Leukemia in the eastern region of Saudi Arabia: A population-based study (1987
      1988).
AB  - This is the first population-based data in Saudi Arabia on the incidence of
      leukemias in the Eastern Region, as conducted by its regional tumor registry.
      Data on cancer were captured from all health facilities in the region in 1987
      1988. Population census was derived from a survey. Data on cancer deaths were
      obtained from all death registries. Crude, age-specific, age-standardized, and
      relative age-standardized incidence rates were used as indicators for the
      incidence of leukemia. There were 124 cases of leukemias registered. The yearly
      average crude incidence rate was 5.2 and 3.6 per 100,000 for Saudi males and
      females, respectively. The age-standardized incidence rate was 7.3 and 6.1 per
      100,000 per year in Saudi males and females respectively. The relative age
      standardized incidence of leukemias in Saudi males and females ranked,
      respectively, third and second highest on the international scale. Death from
      leukemia among Saudis was responsible for 8.9% of the total deaths from cancer.
      Statistical indicators point to a high incidence rate of leukemias in the Eastern
      Region of Saudi Arabia among Saudis. Leukemia was the third leading cause of
      death from cancer. The relative age-standardized rate of leukemias among Saudis
      of either gender rank very high on the international scale.

PMID- 17429231
TI  - Tumor necrosis factor in falciparum malaria.
AB  - To investigate the relationship of TNFalpha levels to Plasmodium falciparum (PF)
      infection, plasma TFNalpha concentrations were measured in Pakistani adults and
      children with mind, severe, cerebral and chronic falciparum malaria and healthy
      (control) subjects. The initial geometric mean plasma concentrations of TFNalpha
      in adult patients with severe malaria (187.6 pg/mL) were significantly higher
      than mild malaria patients (87.1 pg/mL, P < 0.001). TNFalpha levels were not
      correlated to parasite density, cerebral malaria, young age, hypoglycemia or
      fatal outcome; however, they were associated with severe anemia, and hepatic and
      kidney dysfunction. TNFalpha levels were not significantly increased in 16
      patients with hyperparasitemia and were significantly elevated (P < 0.02) in
      chronic malaria patients as compared to control subjects. TNFalpha levels were
      elevated independently in patients with anemia, hypoglycemia (P < 0.001, P <
      0.05), and hepatic and kidney (P < 0.001 each) dysfuntion. In this study, high
      TNFalpha levels were associated with several manifestations of severe malaria and
      were not specific to cerebral malaria and hyperparasitemia.

PMID- 17429232
TI  - Hemoglobin and hematocrit values of Saudi newborns in the high altitude of Abha,
      Saudi Arabia.
AB  - A study was designed to determine the red cell values (hemoglobin and hematocrit)
      of neonates born in the high altitude of Abha and to compare these values with
      known values of other lowland areas of Saudi Arabia. From the cord blood of 587
      normal, appropriate for gestational age and term infants born in 1993 in Abha
      Maternity Hospital, the ranges of Hb and Hct were 130 to 240 g/L and 0.24 to 0.79
      L/L respectively. The mean Hb was 187 g/L. There was no significant difference
      between the male and female values. Also, 17% of the infants in this study were
      polycythemic, while no polycythemia was recorded in these lowland areas, and only
      2% to 4% in the general global newborn population. It was therefore revealed that
      Abha newborns had higher red cell values at birth when compared to other newborns
      in the low altitude areas of Riyadh and Jeddah (P <0.001). We postulate that the
      high altitude (2700 meters above sea level) of Abha, and therefore its relative
      hypoxia, has induced high red cell values in infants born in the city. This
      phenomenon therefore warrants the adoption of higher red cell reference values
      and not necessarily those already documented in other Saudi newborn populations.

PMID- 17429233
TI  - Fungal infection of the nasal activity and paranasal sinuses: Review of 26 cases.
AB  - Fungal infection of the nose and sinuses is an uncommon condition which is now
      being increasingly recognized. In this study we review clinicopathologic features
      in a series of 26 cases encountered at King Faisal Specialist Hospital and
      Research Centre over a five-year period. The cases were divided into four
      categories according to the following histopathologic features: allergic fungal
      sinusitis (11 cases), aspergilloma (one case), chronic indolent fungal sinusitis
      (five cases), and acute fulminant fungal sinusitis (nine cases). In the cases of
      allergic fungal sinusitis and aspergilloma, the fungal hyphae were limited to the
      sinus activity without any evidence of invasion. Invasion in the wall of the
      sinus, as well as the surrounding tissue, was noted in cases of chronic indolent
      fungal sinusitis and acute fulminant fungal sinusitis. All patients were treated
      surgically and those cases with evidence of tissue invasion on pathologic or
      radiologic examination were given antifungal therapy. The prognosis was excellent
      in the cases of allergic fungal sinusitis and aspergilloma. Most of the patients
      with acute fulminant fungal sinusitis died of uncontrolled fungus growth. In the
      cases of chronic indolent fungal sinusitis, all patients are still alive, but two
      patients had loss of vision due to fungal invasion. Fungal sinusitis with absence
      of tissue invasion is easily treated by surgery alone. However, in cases with
      tissue invasion, a combination of surgery with antifungal therapy may be
      successful. Acute fulminant fungal sinusitis, however, has a grave prognosis.

PMID- 17429234
TI  - Screening for iron deficiency anemia in a well baby clinic.
AB  - With a view to combating the long-term effects of iron deficiency anemia in
      infants, we carried out a screening program of infants at nine months of age in
      the Well Baby Clinic. We screened 4751 infants using complete venous blood count
      analysis, 2668 were anemic (Hb <11 gm/dL). Those with hemoglobin less than 10
      gm/dL were recalled to be given iron therapy and further follow-up. Although we
      faced problems with both compliance and follow-up, we felt that it was feasible
      to screen for iron deficiency anemia in the Well Baby Clinic setting. A very high
      prevalence of anemia was found in the population screened. This justified
      continuation of the program, intensifying parent education to comply with iron
      therapy and, more importantly, to teach the proper weaning of their infants to
      prevent iron deficiency anemia.

PMID- 17429235
TI  - Pediatric cancer: The King Faisal Specialist Hospital and Research Centre
      experience.
AB  - Between January 1976 and December 1993, a total of 3291 children with cancer were
      treated at King Faisal Specialist Hospital and Research Centre (KFSH&RC). Males
      accounted for 60.7% and females 39.3%, with a ratio of 1.5:1. The peak age was
      two to five. The three most common malignancies were leukemias (26.2%), lymphomas
      (21.3%), and central nervous system (CNS) tumors (15.3%). This report presents
      some of the epidemiologic data related to the largest number of children with
      malignancy treated in a single institution in Saudi Arabia.

PMID- 17429236
TI  - Vancomycin-resistant enterococci (VRE) as normal flora of the intestine in
      patients at a tertiary care hospital.
AB  - There has been a rapid increase in the incidence of infection and colonization
      with vancomycin-resistant enterococci (VRE) in American and European hospitals in
      the last six years, with fecal carriage reported to be as high as 86% on some
      services. In order to determine the frequency of VRE as normal flora of the
      intestine in Saudi patients, microbiological analysis of stool specimens from
      4276 patients from a tertiary care referral hospital was performed. VRE,
      identified as Enterococcus faecium, was found in six patients. None of the
      patients had any clinical disease associated with VRE. Five were hospitalized
      patients, four with severe underlying diseases; five had a history of prior
      antimicrobial therapy with broad-spectrum antibodies and two of them were treated
      with vancomycin.

PMID- 17429237
TI  - Minor surgery at primary care centers in Riyadh, Saudi Arabia.
AB  - This study was conducted to review the present situation with regard to training,
      facilities and performance of minor surgical procedures in primary care, and to
      look at the way doctors perceive various minor surgical procedures in primary
      care. Randomly selected primary care doctors working in Riyadh health centers
      completed a predesigned confidential questionnaire, which was then mailed to the
      researchers. The questionnaire of data on health centers, such as geographic
      location, size of catchment area population and number and gender of doctors
      working there. In addition, demographic data of doctors who completed the
      questionnaire, as well as their exposure to minor surgery training and
      performance, were recorded. The doctors were then asked about their perception of
      the necessity of performing various minor surgical procedures in primary care
      centers. The study was conducted from June through December of 1994. The
      completed questionnaires were entered into a personal computer for statistical
      analysis using the chi-squared test. Of the 231 doctors who participated in the
      present study, 74% performed some sort of minor surgery during their day-to-day
      work in the health center. Doctors living in remote areas performed more minor
      surgery (MS) compared to other areas and male doctors performed more MS than
      female doctors (P = 0.05). As doctors gained confidence in certain skills such as
      resuscitation, venous cut-down and handling of trauma and fractures, they
      performed more MS compared to those who were not confident. A room allocated for
      MS only was available to 27.7% of doctors, but instruments and equipment were
      available for over 76% of doctors. The doctor's perception of the necessity for
      MS was statisticaly higher among MS performers only in cases of removal of benign
      skin lesions, sebaceous cysts and treatment of burns, compared with non-MS
      performers. There is a great need for provision of facilities and organized
      training courses in minor surgical procedures for primary care doctors and
      nurses.

PMID- 17429238
TI  - X-ray film interpretation by hospital outpatient departments and primary health
      care center physicians in Dammam, Saudi Arabia.
AB  - The objective of this study was to assess the accuracy of x-ray film
      interpretation by nonradiologist physicians. This was a cross-sectional study
      based on data collected using a structured check-list from a sample of 863 x-ray
      films requested and interpreted by physicians working in the outpatient
      departments of Dammam Central Hospital, and in five primary health care centers
      in Dammam city, Saudi Arabia. The check-list was used to compare the physicians'
      interpretations of x-ray films requested with those made by an experienced
      consultant radiologist. Physicians' interpretations were classified as concordant
      or discordant with those of the radiologists. Factors affecting those
      interpretations were assessed. Physicians from both the hospital and primary
      health care centers were discordant with the radiologist in 20.0% and 22.2% of x
      ray films interpreted. There were significant positive correlations of
      physicians' interpretations with physicians' handwriting and completeness of
      patient information on the request forms, quality of x-ray films and adequacy of
      x-ray film views. Also, there were significant negative correlations of
      interpretations with chest and head and neck x-ray films. The study reveals a
      significant need for training of hospital and primary health care center
      physicians in diagnostic radiology.

PMID- 17429239
TI  - Hypopharyngeal carcinoma: King Faisal Specialist Hospital and Research Centre
      experience.
AB  - From 1975 to 1985, 202 patients with hypopharyngeal cancer were seen at King
      Faisal Specialist Hospital and Research Centre (KFSH&RC). The endoscopic
      investigation showed that 28.3% of these patients had postcricoid carcinoma;
      19.85% had pyriform fossa carcinoma and 52.9% had involvement of both sites. The
      pathological diagnosis of all cases was squamous cell carcinoma type. The
      majority of the patients (62.98%) had T4 lesions, which showed a late
      presentation to KFSH&RC. Information related to survival was available for a
      smaller number of patients due to many "lost-to-follow-up" cases. The overall
      median survival time was 8.5 months (1-110 months). The survival rate for each
      site was calculated, as well as the staging of the disease and treatment modality
      used. It appeared that pyriform fossa (median 21 months) had the best survival
      rate. In addition, the earlier the lesion was detected and the more aggressive
      the treatment applied, the better the survival rate. Fifty percent of the
      patients receiving radiation therapy and surgery had a five-year survival rate.
      Factors other than smoking and/or drinking should be looked for in our community
      as predisposing to this disease in our population.

PMID- 17429240
TI  - Fiberoptic, conventional and combination phototherapy for treatment of
      nonhemolytic hyperbilirubinemia in neonates.
AB  - The objective of this prospective, randomized study was to compare the
      effectiveness of fiberoptic, conventional and a combination phototherapy in
      decreasing bilirubin concentrations in neonatal nonhemolytic hyperbilirubinemia.
      Forty-six infants who were 36 weeks' gestation and more were randomly assigned to
      fiberoptic phototherapy (n=16) (Biliblanket, Ohmeda), conventional daylight
      phototherapy (n=15) and combination phototherapy (n=15) (fiberoptic and
      conventional). The groups were similar in clinical characteristics at study entry
      in terms of birth weight, age and bilirubin concentration. There were no
      statistically significant differences in the duration of treatment among the
      three groups (P=0.83). There were also no statistically significant differences
      among the three groups in the serum bilirubin concentrations at 24 hours, 48
      hours, end of phototherapy, and 24 hours postphototherapy. We concluded that the
      decrease in serum bilirubin concentration was comparable among fiberoptic,
      conventional and combination phototherapy groups.

PMID- 17429241
TI  - Surgery for postintubation tracheal and tracheosubglottic stenotic lesions.
AB  - Postintubation tracheal stenosis is a recognized problem. Although its incidence
      has recently decreases, it is still a difficult complication to treat. We have
      reviewed our experience with 10 patients with tracheal stenosis over the last
      five years between 1990 and 1995. There were seven male and three female patients
      with an average age of 14.2 +/- 4 years (range 6 to 48 years). Resection and
      reconstruction with primary anastomosis was performed in seven patients, while
      conservative treatment with dilatation was performed in two patients. One patient
      refused surgery. Operations performed included resection of tracheocricoid
      segment with tracheothyroid anastomosis (N=3) and tracheal resection with end-to
      end anastomosis (N=4). The resected airway segment ranged from 3 cm to 6 cm. In
      view of the intense inflammatory and fibrotic process in and around the stenotic
      segment, the practice of tracheostomy for the relief of postintubation acute
      tracheal obstruction should not be taken lightly, as it adds not only to the
      severity of the inflammatory process, but also increases the length of the
      tracheal segment to be resected. Postoperatively, all patients were extubated;
      this was accomplished by the end of surgery in six patients, while the seventh
      patient was extubated three weeks later. There was no mortality in this series.
      When normal functional activity and airway patency were taken as two parameters
      to judge the outcome of surgery, results were good in six (86%) patients and
      satisfactory in one. These results support the validity of one-stage
      reconstruction approach as one alternative for the treatment of postintubation
      tracheal and tracheosubglottic stenotic lesions.

PMID- 17429242
TI  - A study of clinical and allergic aspects of rhinitis patients in Riyadh.
AB  - Eighty consecutive patients presenting with variable nasal symptoms were
      investigated. Fifty-three (66.25%) were identified as allergic and 27 (33.5%) as
      having nonallergic rhinitis. Medical history and clinical examination alone
      seemed to be inadequate in establishing a diagnosis, since the main complaints,
      i.e., nasal itching, sneezing and runny rose, occurred with the same frequency in
      both groups. However, alternating nasal blockage and sneezing were prominent in
      the allergic group (80.40%), while perennial symptoms were more evident in the
      nonallergic group (68%). There were no striking differences between the two
      groups in the occurrence of nasal septal deviation or in evidence of nasal
      polyps. In the allergic groups, sensitivities to indoor allergens, i.e.,
      cockroaches, cat fur, house dust, as well as to pollens, were very prominent.
      Among the nonspecific provoking factors, dust, strong smells, smoke and stress
      seem to be important.

PMID- 17429243
TI  - Chronic idiopathic ulcerative colitis in Saudi Arabia: A clinicopathological
      study of 76 cases.
AB  - In this report we present our experience with 76 cases of chronic idiopathic
      ulcerative colitis (IUC) out of 1279 consecutive colorectal biopsies (6.0%), seen
      during an 11-year period (1983-1994), in a tertiary care teaching hospital.
      During the same period, 12 (0.8%) patients with Crohn's disease were seen. Of the
      76 patients with IUC, forty-nine were male and 27 were female, with an age range
      of six to 88 years, a mean of 38 +/- 16 and a median of 36 years. Forty-nine
      patients were Saudi Nationals (27M, 22F), 21 were non-Saudi Arabs and six were
      Asians. In most patients, the onset of IUC was at 20 to 49 years (70%). The
      disease duratio at diagnosis ranged from one month to five years, with a median
      of 12 months. The follow-up period ranged form 13 months to 11 years, with a
      median of three years. Diarrhea, hematochesia and abdominal pain were the
      dominant symptoms. The disease grade was generally of mild to moderate severity
      (55 patients, 72%) and was of low stage (distal involvement in 69 patients, 91%).
      The rarity of skin manifestations and of development of colonic cancer is to be
      noted in spite of the relatively short period of follow-up. Our findings compare
      with experience from the region, confirming the mild course of the disease as
      contrasted to Western experience. These findings will be discussed.

PMID- 17429244
TI  - Current trends in the management of homozygous b-thalassemia.

PMID- 17429245
TI  - Sensorineural hearing loss in homozygous sickle cell disease in Qatif, Saudi
      Arabia.
AB  - Sensorineural hearing loss (SNHL) is a known complication of sickle cell disease
      (SCD). There is a paucity of information on this problem in Sausi SCD patients. A
      prospective controlled study was conducted over 27 months in Qatif Central
      Hospital. One hundred patients with sickle cell anemia (SCA), aged five to 40
      years, were studied. The control group consisted of 100 healthy individuals. A
      detailed history, otologic and audiologic examinations were carried out on both
      groups. Further investigations to rule out local retrocochlear pathology were
      performed on those having unilateral SNHL. No case of SNHL was detected in the
      control group, while it was recorded in 19 (19%) of SCA patients, 13 males and
      six females. There was a significant association between the SNHL and the onset
      of first vaso-occlusive crisis at six years of age or less. There was no
      significant difference in the frequency of SNHL between children and adults.
      Twenty-one percent of patients who had SNHL completely recovered. Patients with
      SCD need a careful regular hearing assessment. Those detected to have SNHL need a
      careful plan implemented by both the clinician and otolaryngologist for proper
      care of this important complication.

PMID- 17429246
TI  - What's your diagnosis: Cerebellar hemangio-blastoma.

PMID- 17429247
TI  - b-thalassemia major: Experience at King Fahad Hofuf Hospital, Al-Hassa, Saudi
      Arabia.

PMID- 17429248
TI  - Outcome in elective and emergency cesarean sections: A comparative study.
AB  - To study the obstetrics outcome of cesarean sections (CS) in relation to the
      elective or emergency nature of this procedure, a comparative study was conducted
      on 1426 females whose deliveries were by CS in King Khalid University Hospital
      (KKUH). Of the various factors analyzed in relation to the two types of CS,
      statistically significant associations were found between emergency CS and
      younger patients, low parity, irregular attendance at antenatal clinics,
      complications in labor, postoperative morbidity and low Apgar score(>6). It was
      concluded that every effort should be directed to effect-planned CS, as
      determined during the antenatal period, if possible, so as to reduce the various
      problems associated with emergency CS. The chances are that this approach is
      unlikely to influence the overall CS rate in either way.

PMID- 17429249
TI  - Recurrent allergic fungal sinusitis sequentially caused by Exserohilum and
      Bipolaris.

PMID- 17429250
TI  - Subchorionic hematoma in threatened abortion: Sonographic evaluation and
      significance.
AB  - In a study of 92 women with subchorionic hematoma evaluated with sonographic scan
      in King Khalid University Hospital, it was found that the mean ages and live
      births of patients who carried their pregnancies to viability were higher when
      compared with the patients who aborted. There was a statistically significant
      association between the gestational age at diagnosis of subchorionic hematoma and
      the size of the hematoma. There was, however, no statistically significant
      association found between the gestational age at diagnosis, size and site of the
      hematoma and the outcome of pregnancy. It was concluded that subchorionic
      hematoma which appear either in the second trimester, or are larger, or located
      in the lower uterine segment, may be associated with higher rates of abortion or
      preterm deliveries. Nevertheless, there is no statistically significant impact of
      these on the outcome of pregnancy.

PMID- 17429251
TI  - Large bony lesion of the penis.

PMID- 17429252
TI  - Common G6PD variant from Saudi population and its prevalence.
AB  - Biochemical characterization of erythrocyte glucose-6-phosphate-dehydrogenase
      from 18 unrelated deficient Saudi Subjects from Al-Hassa and Al-Qatif areas of
      the Eastern Province was carried out according to WHO procedures. This had led to
      the identification of one genetically determined common variant, "G6PD
      Mediterranean". The overall prevalence rate of this deficiency in these areas was
      determined to be in excess of 42%. None of the subjects studied displayed any
      sign of favism, a condition usually associated with G6PD Mediterranean, which is
      characterized by a very low intracellular enzyme activity.

PMID- 17429253
TI  - Ileocolic intussusception with Trichuris trichiura infestation: A case report.

PMID- 17429255
TI  - Applications of the polymerase chain reaction to infectious disease diagnosis.

PMID- 17429254
TI  - Granular acute lymphoblastic leukemia: Report of two cases and review of the
      literature.

PMID- 17429256
TI  - Profile of medical research publications from the GCC countries, 1990-1994.
AB  - Using the CD-ROM system of MEDLINE, which contains the origins of articles that
      are published in about 3500 international medical journals, a survey was
      performed on the medical publications from the six countries in the Gulf
      Cooperating Council (GCC) over a period of five years (1990-1994). The Kingdom of
      Saudi Arabia was the largest producer of publications, with approximately 400
      papers each year. In the same period the output from Kuwait declined from about
      200 to a lower number, an effect probably caused by the invasion. In contrast,
      the United Arab Emirates, and to a lesser extent the Sultanate of Oman, have
      shown a growth in their publication record due to the initiation of new medical
      schools in these two countries. In the six GCC countries, all the colleges of
      medicine together were responsible for 34% of the total number of publications,
      hospitals and health centers published 45% of all papers, while non-medical
      colleges and other institutions published smaller amounts (10% and 11%
      respectively).

PMID- 17429257
TI  - Esophageal atresia with tracheoesophageal fistula and congenital esophageal
      stenosis: A case report and review of the literature.

PMID- 17429258
TI  - Susceptibility of Haemphilus influenzae to selected antimicrobial agents.

PMID- 17429259
TI  - Quantifying handicap in institutionalized patients in the eastern province of
      Saudi Arabia.

PMID- 17429260
TI  - Hibernoma: A new case in the submandibular region.

PMID- 17429261
TI  - Brucellosis: A model for eradication of endemic diseases from the Arabian
      peninsula.

PMID- 17429262
TI  - Chronic colitis after Aeromonas hydrophilia infection.

PMID- 17429263
TI  - Difficult diagnosis in a patient with multiple osteoblastic thoracic vertebral
      lesions.

PMID- 17429264
TI  - Gastric teratoma: A rare cause of upper gastrointestinal bleeding in neonates.

PMID- 17429265
TI  - Pasteurella multocida empyema.

PMID- 17429266
TI  - Traumatic rupture of the diaphragm: A rare cause of pneumoperitoneum.

PMID- 17429267
TI  - Maternal mortality.

PMID- 17429268
TI  - High-level, multiresistant enterococci associated with systemic disease: A report
      of two cases.

PMID- 17429269
TI  - Acromegaly-like features in a patient with severe Acanthosis nigricans and
      insulin resistance.

PMID- 17429271
TI  - AIDS in jordan.

PMID- 17429270
TI  - Severe hereditary hemochromatotic cardiomyopathy responsive to small-volume
      venesections combined with deferoxamine.

PMID- 17429272
TI  - Spinal enterognous cysts: A clinical, morphological and radiological study of
      three cases.

PMID- 17429274
TI  - Dubin-Johnson syndrome in a Saudi neonate.

PMID- 17429277
TI  - A syndrome of premature senility in two Jordanian families.

PMID- 17429278
TI  - Prevalence of HBV, HCV, and HIV infections among family blood donors.

PMID- 17429279
TI  - Congenital thyroxine-binding globulin deficiency detected by newborn screening
      for hypothyroidism.

PMID- 17429280
TI  - Clavicle fracture and brachial plexus palsy in the newborn: Risk factors and
      outcome.

PMID- 17429281
TI  - Functional endoscopic sinus surgery: University of Ottawa experience and an
      overview.

PMID- 17429282
TI  - Agenesis of the hemidiaphragm.

PMID- 17429286
TI  - The relationship between angiotensin-converting enzyme (insertion/deletion) gene
      polymorphism and left ventricular remodeling in acute myocardial infarction.
AB  - BACKGROUND: The development of left ventricular remodeling after acute myocardial
      infarction is a predictor of heart failure and mortality. The genetic influence
      on cardiac remodeling in the early period after acute myocardial infarction, is
      however, unclear. The aim ofthis study was to investigate the relationship
      between angiotensin-converting enzyme (ACE) gene polymorphism and left
      ventricular remodeling in the early period in patients with anterior myocardial
      infarction. METHOD: The study population consisted of 142 patients with their
      first attack of acute anterior myocardial infarction. Echocardiographic
      examinations were performed within 24 h of the first attack (first evaluation)
      and on the fifth day of acute myocardial infarction (second evaluation). Left
      ventricular end systolic and diastolic diameters, left ventricular end systolic
      and diastolic volumes, ejection fraction, mitral flow velocities (E, A, E/A),
      deceleration time, isovolumic relaxation time and myocardial performance index
      were calculated. ACE I/D polymorphism was determined using polymerase chain
      reaction amplification. RESULTS: On the basis of polymorphism of the ACE gene,
      the patients were classified into the three groups: group 1, deletion/deletion
      (n=59) genotype, group 2 insertion/deletion (n=69), and group 3
      insertion/insertion (n=14) genotype. When the first and second sets of
      echocardiographic results of the groups were compared, all parameters were not
      different among three groups. In group analysis, Left ventricular systolic
      diameters, left ventricular diastolic diameters, left ventricular end diastolic
      diameters, left ventricular ejection fraction and myocardial performance index
      between first and second echocardiographic results were significantly different
      in deletion/deletion group and only myocardial performance index and left
      ventricular ejection fraction in insertion/deletion group (P<0.05). CONCLUSIONS:
      ACE gene polymorphism may influence early cardiac remodeling after acute
      myocardial infarction. Patients with the deletion/deletion-insertion/deletion
      genotype may be particularly more sensitive to ACE-I treatment possibly owing to
      the more prominent role of the renin-angiotensin system.

PMID- 17429287
TI  - The association between androgen levels and premature coronary artery disease in
      men.
AB  - OBJECTIVE: The relationship between androgens and the risk of development of
      coronary artery disease has not been clarified well. This study was planned to
      determine the relationship between serum androgen levels and premature
      development of coronary artery disease in men. METHODS: Sixty-nine men below 45
      years of age with documented coronary artery disease (mean age 41.0+/-4.7)
      constituted the study group. Control group consisted of 56 men with similar age
      and normal coronary angiograms (mean age 41.3+/-3.8). Total and free
      testosterone, estradiol, and fasting plasma total, low-density lipoprotein, and
      high-density lipoprotein cholesterol, and triglyceride levels were measured, and
      compared between the two groups. RESULTS: Mean age, body mass index, and the
      frequency of hypertension were similar between the two groups; however, diabetes
      mellitus, smoking, hyperlipidemia, and family history of coronary artery disease
      were more frequent in the coronary artery disease group. Total and free
      testosterone levels of the patients with coronary artery disease were
      significantly lower than those of controls, whereas estradiol levels did not
      differ. Multivariate logistic regression analysis revealed that free testosterone
      levels (P=0.014; odds ratio=0.90; 95% confidence interval=0.87-0.99),
      hyperlipidemia (P<0.001; odds ratio=8.2; 95% confidence interval=3.17-21.0), and
      smoking (P=0.026; odds ratio=3.12; 95% confidence interval=1.15-8.48) were
      independent predictors of premature coronary artery disease. Moreover, using
      receiver operating characteristic analysis, patients with free testosterone
      levels below the cut-off value of 17.3 pg/ml had an adjusted 3.3-fold risk of
      developing premature coronary artery disease compared to those with free
      testosterone levels above the cut-off level (odds ratio=3.3; 95% confidence
      interval=1.57-6.87). CONCLUSION: A low level of free testosterone may be related
      to the development of premature coronary artery disease.

PMID- 17429288
TI  - Metabolic syndrome: stronger association with coronary artery disease in young
      men in comparison with higher prevalence in young women.
AB  - BACKGROUND: Being overweight, a constituent of the metabolic syndrome, is also an
      important contributing factor to the development of coronary artery disease in
      younger patients, compared with the older patient population. Owing to the above
      mentioned fact, we sought to assess the association of the metabolic syndrome
      with premature coronary artery disease. METHODS: In an analytic cross-sectional
      study, 940 patients (553 women<or=55 years and 387 men<or=45 years), 637 with
      coronary artery disease and 303 without coronary artery disease, were evaluated.
      The extent of atherosclerosis was assessed with a clinical vessel score. Besides
      established coronary artery disease risk factors, all patients were evaluated for
      the presence of metabolic syndrome based on the National Cholesterol Education
      Program Adult Treatment Panel III criteria. RESULTS: The overall prevalences of
      metabolic syndrome and coronary artery disease were 56 and 67.8%, respectively.
      Metabolic syndrome prevalence was higher in women than in men (69.6 vs. 36.4%,
      P<0.001). The odds ratio of metabolic syndrome for premature coronary artery
      disease was 1.82 (95% confidence interval 1.17-2.82) after adjusting for age and
      multiple established coronary artery disease risk factors; the strength of this
      association varied by sex (2.17 in men vs. 1.22 in women). CONCLUSIONS: This
      study revealed a stronger association between metabolic syndrome and coronary
      artery disease in men<or=45 years than in women<or=55 years. It seems that
      endogenous estrogens may play a role in reducing the effects of metabolic
      syndrome-related risk and therefore in spite of higher prevalence of metabolic
      syndrome in young women, the effect of this syndrome on coronary artery disease
      is more dominant in young men.

PMID- 17429289
TI  - The effect of collateral circulation on left ventricular systolic function.
AB  - BACKGROUND: Conflicting reports exist on the influence of coronary collateral
      circulation on preservation of left ventricular systolic function. The aim of
      this study was to assess the effect of coronary collateral circulation on left
      ventricular systolic function in coronary artery disease. METHODS: Seventy-one
      consecutive patients having left anterior descending arteries with proximal or
      near-proximal stenosis of at least 95% (excluding 100%) were included in the
      study. The coronary collateral circulation to left anterior descending artery was
      evaluated with regard to its effects on left ventricular systolic function.
      RESULTS: Among the 71 patients, 46 patients were found to have a coronary
      collateral circulation grade of >or=1 (group 1), whereas the remaining 25
      patients had coronary collateral circulation grade of 0 (group 2). The mean value
      of left ventricular function score in group 1 was higher than that of group 2
      (3.69+/-2.34 vs. 2.00+/-1.55, P=0.002), whereas the mean value of left
      ventricular ejection fraction in group 1 was lower than that of group 2 (44.67+/
      12.05 vs. 54.32+/-10.22, P=0.001). The value of coronary collateral circulation
      grade was found to be positively correlated with the value of left ventricular
      function score (P=0.01, r=0.3), and negatively correlated with the value of left
      ventricular ejection fraction (P=0.01, r=-0.3). CONCLUSION: Coronary collateral
      circulation to the severely stenotic left anterior descending artery was not
      found to have an improving effect on left ventricular systolic function. In
      contrast with the previous studies demonstrating the coronary collateral
      circulation-associated preservation of left ventricular systolic function,
      presence of coronary collateral circulation was found to accompany or be
      associated with impairment of left ventricular systolic function. The grade of
      coronary collateral circulation was also found to be positively correlated with
      the severity of left ventricular systolic dysfunction. Further research on larger
      patient populations based on a long-term follow-up is warranted to investigate
      this issue.

PMID- 17429290
TI  - Noninvasive assessment of coronary artery ectasia using multidetector computed
      tomography.
AB  - OBJECTIVES: The aim of this study is to determine the prevalence of coronary
      artery ectasia and its relationship to atheromatous changes in participants
      undergoing coronary computed tomography angiography. BACKGROUND: Coronary artery
      ectasia occasionally encountered on conventional coronary angiography is
      considered a manifestation of atherosclerosis. METHODS: Four hundred consecutive
      participants, 300 men (mean age 56 years) who underwent coronary computed
      tomography angiography were evaluated. Coronary artery ectasia was defined as an
      arterial segment with a diameter of at least 1.5 times the diameter of the
      adjacent normal coronary artery. The prevalence and location of coronary artery
      ectasia as well as concomitant atherosclerotic changes were evaluated. The
      association of coronary artery ectasia with coronary risk factors was also
      studied. RESULTS: Coronary artery ectasia was encountered in 31 participants
      (8%), 29 men. The right coronary artery was most commonly affected with ectasia
      (50%) and most participants had single-vessel involvement (74%). Twenty-six of 31
      participants (84%) had coexisting atheromatous wall changes or insignificant
      coronary artery disease; four participants out of 31 (13%) had significant
      coronary artery disease. Coronary artery ectasia thrombosis was found only in one
      patient (3%). No apparent correlation was present between coronary artery ectasia
      and diabetes mellitus, hypertension, hyperlipidemia, smoking and family history
      of coronary artery disease. CONCLUSION: The prevalence of coronary artery ectasia
      in consecutive participants who underwent coronary computed tomography
      angiography is 8%. The right coronary artery was most commonly affected and most
      participants had single-vessel involvement. Coronary artery ectasia usually is
      associated with atheromatous changes, but not with significant coronary artery
      disease. Coronary artery ectasia thrombosis was a rare complication. No specific
      predisposing factors have been identified.

PMID- 17429291
TI  - Clinical impact of the troponin 99th percentile cut-off and clinical utility of
      myoglobin measurement in the early management of chest pain patients admitted to
      the Emergency Cardiology Department.
AB  - OBJECTIVE: To verify the clinical impact of different low cut-offs for troponin
      I/cardiac troponin I (99th percentile to 10% CV) and for myoglobin, in early risk
      stratification of patients with suspected acute coronary syndrome. METHODS: A
      total of 516 consecutive non-ST-elevation patients admitted to hospital were
      followed. The first measurement of cardiac markers was performed at the point-of
      care in the Emergency Cardiology Department, using Stratus CS. The lowest cardiac
      troponin I concentration with a CV<or=10% (cardiac troponin I concentration=0.07
      microg/l) was used to perform an early diagnosis of cardiac damage and to admit
      non-ST-elevation patients to the Intensive Cardiac Unit. Final diagnosis of acute
      myocardial infarction was assessed according to European Society of Cardiology
      and American College of Cardiology diagnostic criteria: cardiac marker follow-up
      after hospital admission was performed in central laboratory. We retrospectively
      assessed how the diagnostic accuracy of an early diagnosis of myocardiac damage
      in the same population might have changed if different lower cardiac troponin I
      cut-offs had been used upon admitting patients in the Emergency Cardiology
      Department, independently from the analytical imprecision of the method. RESULTS:
      A diagnosis of acute myocardial infarction was performed on 110 (21.3%) of 516
      non-ST-elevation-patients admitted to hospital. Seventy (13.6%) patients had
      cardiac troponin I >0.07 microg/l in the Emergency Cardiology Department
      (P>0.05). Using lowering cut-off values, the difference between the fraction of
      patients that was positive compared with the diagnosis according to European
      Society of Cardiology and American College of Cardiology criteria and had
      remained statistically significant (P<0.05) up to 0.03 microg/l (99th percentile
      upper reference limit) was considered (85 patients, 16.5%, n.s.). Relative
      operating characteristic analysis confirmed that the best clinical cut-off was
      related to the cardiac troponin I concentration that meets the 99th percentile
      upper reference limit. The diagnostic accuracy of myoglobin in detecting the
      minimum cardiac damage was significantly lower, independently from the cut-offs
      considered. CONCLUSION: The diagnostic accuracy in detecting myocardial damage
      early in the Emergency Cardiology Department improves when the 99th percentile is
      used as a decisional value of cardiac troponin I; the use of this cut-off makes
      the measurement of myoglobin unnecessary.

PMID- 17429292
TI  - The long prognostic value of wall motion abnormalities during the recovery phase
      of dobutamine stress echocardiography after receiving acute beta-blockade.
AB  - OBJECTIVE: To assess the prognostic value of wall motion abnormalities during the
      recovery phase of dobutamine stress echocardiography in addition to wall motion
      abnormalities at peak stress. METHODS: Wall motion abnormalities were assessed at
      peak and during recovery phase of dobutamine stress echocardiography in 187
      consecutive patients, who were followed for occurrence of cardiac events.
      RESULTS: During follow-up (mean 36+/-28 months), 19 patients (10%) died from
      cardiac causes, 34 (18%) patients suffered nonfatal myocardial infarction, and 77
      (41%) patients underwent late revascularization. Univariable predictors of
      cardiac events by Cox regression analysis were age (hazard ratio: 1.01;
      confidence interval: 1.00-1.03), dyslipidemia (hazard ratio: 1.41; confidence
      interval: 1.02-1.95), rest wall motion abnormalities (hazard ratio: 1.37;
      confidence interval: 1.14-1.64), new wall motion abnormalities (hazard ratio:
      1.18; confidence interval: 0.95-1.45) at peak and new wall motion abnormalities
      (hazard ratio: 1.33; confidence interval: 1.11-1.59) at recovery phase of
      dobutamine stress echocardiography. The best multivariable model to predict
      cardiac events included new wall motion abnormality (hazard ratio: 5.34;
      confidence interval: 1.71-16.59) at recovery phase of dobutamine stress
      echocardiography, after controlling for clinical and peak dobutamine stress
      echocardiography data. CONCLUSIONS: Myocardial ischemia at recovery phase of
      dobutamine stress echocardiography is an independent predictor of cardiac events
      and has an incremental value when added to ischemia at peak.

PMID- 17429293
TI  - Periprocedural and medium-term antithrombotic strategies in patients with an
      indication for long-term anticoagulation undergoing coronary angiography and
      intervention.
AB  - OBJECTIVES: The optimal antithrombotic treatment for patients on long-term
      anticoagulation undergoing invasive coronary procedures is currently undefined.
      The strategies adopted periprocedurally and medium-term after coronary stenting
      (percutaneous coronary intervention with stent implantation) at our Institution,
      were reviewed, and the safety and efficacy of the various regimens evaluated.
      METHODS: All patients undergoing invasive coronary procedures between January
      2002 and December 2004 were retrospectively identified. RESULTS: Out of 3709
      patients overall, 104 (2.8%; 95% confidence interval 2.3-3.4) were on warfarin
      (because of atrial fibrillation in >50% of cases), whereas this was the case for
      49 (3.1%; 95% confidence interval 2.3-4.1) of 1584 undergoing percutaneous
      coronary intervention with stent implantation. The antithrombotic strategies were
      highly variable, both periprocedurally (i.e. warfarin withdrawal or substitution
      by heparin, followed by aspirin with or without a thienopyridine) and medium-term
      after percutaneous coronary intervention with stent implantation (i.e.
      combination of warfarin and single or dual antiplatelet agents or pure dual
      antiplatelet treatment). Overall, periprocedural hemorrhages occurred in five
      patients (4.8%; 95% confidence interval 1.56-11.22). No thromboembolic events
      were observed, whereas one subacute stent thrombosis occurred (2%; 95% confidence
      interval 0.05-11) during warfarin and aspirin treatment. Among patients
      undergoing percutaneous coronary intervention with stent implantation, 1-month
      hemorrhagic rate was 10% (95% confidence interval, 3.3-23.8); most hemorrhages
      (major bleeds in three-quarters of cases) occurred during triple therapy with
      warfarin (or low-molecular-weight heparin), aspirin and a thienopyridine.
      CONCLUSIONS: At our Institution (where standardized protocols are currently not
      in use), periprocedural and medium-term antithrombotic treatment in patients on
      long-term anticoagulation undergoing percutaneous coronary intervention with
      stent implantation showed substantial variability. As a result of the relevant 1
      month complication rate, further properly sized and designed studies are
      warranted to identify the optimal strategies for this patient subset, which is
      foreseen to progressively increase over the next years.

PMID- 17429294
TI  - Low-density lipoprotein reduction by simvastatin is accompanied by angiotensin II
      type 1 receptor downregulation, reduced oxidative stress, and improved
      endothelial function in patients with stable coronary artery disease.
AB  - OBJECTIVES: We tested the hypothesis that low-density lipoprotein-cholesterol
      induces angiotensin II type 1 receptor upregulation that, in turn, accounts for
      enhanced oxidative stress, and the subsequent endothelial dysfunction in patients
      with coronary artery disease. METHODS: Brachial artery flow-mediated
      vasodilation, serum 8-iso-prostaglandin F2alpha (8-isoprostane), and angiotensin
      II type 1 receptor density on platelets were measured in 19 patients with
      coronary artery disease, at entry and after 12 weeks of simvastatin therapy, 40
      mg/day. RESULTS: At entry there was a significant linear correlation between:
      angiotensin II type 1 receptor density and plasma low-density lipoprotein
      cholesterol; plasma 8-isoprostane and angiotensin II type 1 receptor density; and
      flow-mediated vasodilation and 8-isoprostane. Simvastatin therapy reduced low
      density lipoprotein-cholesterol, downregulated angiotensin II type 1 receptor,
      decreased 8-isoprostane, and improved flow-mediated vasodilation. The slopes of
      the presimvastatin and the postsimvastatin angiotensin II type 1 receptor/low
      density lipoprotein relationships did not significantly differ, indicating that
      simvastatin caused a downregulation of angiotensin II type 1 receptor that could
      be predicted by the low-density lipoprotein reduction. In addition, simvastatin
      mediated changes in 8-isoprostane could be predicted by angiotensin II type 1
      receptor downregulation, and flow-mediated vasodilation improvement by changes in
      8-isoprostane. A significant correlation existed between simvastatin-mediated
      changes in 8-isoprostane and angiotensin II type 1 receptor. CONCLUSION: The
      results of this study are consistent with the hypothesis that in coronary artery
      disease, the impairment of endothelial function is strongly associated with
      oxidative stress, oxidative stress with cellular angiotensin II type 1 receptor
      density, and the angiotensin II type 1 receptor density with low-density
      lipoprotein-cholesterol, suggesting cause-effect relationships between these
      variables. In support for this notion, these baseline associations were not
      significantly disturbed by low-density lipoprotein-lowering therapy with
      simvastatin.

PMID- 17429295
TI  - Increased plasma levels of cystatin C and transforming growth factor-beta1 in
      patients with coronary artery ectasia: can there be a potential interaction
      between cystatin C and transforming growth factor-beta1.
AB  - Cystatin C, known as an inhibitor of the cathepsin family of cysteine proteases,
      has been evaluated in several cardiovascular disorders such as atherosclerosis
      and acute myocardial infarction. The potential interaction between transforming
      growth factor-beta1 and cystatin C has also been demonstrated in some cell types.
      Accordingly, we aimed to compare the plasma levels of cystatin C and transforming
      growth factor-beta1 in patients with coronary artery ectasia coexisting with
      coronary artery disease and those with coronary artery disease alone. Thirty-nine
      patients with coronary artery ectasia and coronary artery disease and 35 age and
      sex-matched patients with coronary artery disease alone were prospectively
      enrolled in the study. Blood samples of all patients and control participants for
      measuring plasma cystatin C and transforming growth factor-beta1 levels were
      drawn>or=24 h after the coronary angiography. Cystatin C concentrations in plasma
      were measured by latex-enhanced reagent on a Behring Nephelometer II. Plasma
      levels of transforming growth factor-beta1 were measured by using transforming
      growth factor-beta1 enzyme-linked immunosorbent assay kit (BioSource
      International, Inc., Camarillo, California, USA). Plasma level of cystatin C was
      significantly higher in patients with coronary artery ectasia+coronary artery
      disease than in patients with coronary artery disease alone (1.05+/-0.30 mg/dl
      vs. 0.92+/-0.18 mg/mdl, P=0.025, respectively). Transforming growth factor-beta1
      was also found to be significantly higher in patients with coronary artery
      ectasia+coronary artery disease compared with those with coronary artery disease
      (2.47+/-0.43 vs. 2.22+/-0.43 pg/ml, P=0.02, respectively). The plasma level of
      cystatin C was significantly but weakly correlated with that of transforming
      growth factor-beta1 (r=0.217 P=0.02). We conclude that plasma levels of cystatin
      C and transforming growth factor-beta1 are significantly higher in patients with
      combined coronary artery ectasia and coronary artery disease than in those with
      coronary artery disease. Correlation between transforming growth factor-beta1 and
      cystatin C may also suggest that pathogenesis of coronary artery ectasia might
      have some different pathways from atherosclerosis with respect to the regulation
      of extracellular matrix remodeling. Therefore, the role of cystatin in the
      pathogenesis of coronary artery ectasia and its potential interaction with
      transforming growth factor-beta1 should be evaluated in further studies.

PMID- 17429296
TI  - Potent mitochondria-targeted peptides reduce myocardial infarction in rats.
AB  - OBJECTIVE: Previously, we demonstrated that a novel opiate peptide, 2',6'
      dimethyl-tyrosine-D-Arg-Phe-Lys-NH2, provided cardioprotection against myocardial
      stunning in vivo. We subsequently showed that this peptide targeted mitochondria
      and can scavenge reactive oxygen species. The objective of this study was to
      determine the role of opioid versus antioxidant activity in cardioprotection.
      METHODS: We compared two mitochondria-targeted peptide analogs that lacked opioid
      activity: SS-31 (D-Arg-2',6'-dimethyl-tyrosine-Lys-Phe-NH2) and SS-20 (Phe-D-Arg
      Phe-Lys-NH2). They differ in that only SS-31 has scavenging ability. Rats
      (n=8/group) were randomized to SS-31, SS-20 or placebo. The drugs (3 mg/kg) or
      saline was administered intraperitoneally 30 min before ligation of the left
      anterior descending artery for 60 min, and another dose given intraperitoneally 5
      min before reperfusion for 60 min. Study endpoints included myocardial infarct
      size, cardiac arrhythmia and myocardial lipid peroxidation. RESULTS: The area at
      risk was similar among the groups. The infarct area/area at risk, however, was
      significantly smaller in the treatment groups (53.9+/-1.1% in SS-31 group, 47.1+/
      1.4% in SS-20 group, versus 59.9+/-1% in the controls, P<0.01). Lipid
      peroxidation was significantly reduced by both SS-31 and SS-20 treatment.
      Arrhythmia occurred only during the early period of coronary occlusion and was
      less frequent and less severe in the peptide treatment groups than in the
      controls (Lambeth score 5 points, 3 points, versus 13 points in the controls,
      P<0.05). CONCLUSIONS: This study shows that pretreatment with both SS-31 and SS
      20 significantly reduced myocardial lipid peroxidation and infarct size in
      ischemia-reperfusion injury, and suggests that the cardioprotective properties of
      2',6'-dimethyl-tyrosine-D-Arg-Phe-Lys-NH2 was primarily mediated by its
      antioxidant properties. As SS-20 does not scavenge reactive oxygen species, it
      most likely reduces reactive oxygen species production during ischemia
      reperfusion.

PMID- 17429297
TI  - Adipose tissue stromal cells transplantation in rats of acute myocardial
      infarction.
AB  - OBJECTIVE: This study was to investigate the proliferation and differentiation of
      rat adipose stromal cells when implanted into ischemic myocardium and the
      improvement of heart function. METHODS: Sprague-Dawley rat adipose tissue was
      digested with collagenase type I solution and adipose stromal cells were derived
      by culture. The cells' surface phenotype was examined by flow cytometry. Adipose
      stromal cells labeled with 4'6-diamidino-2-phenylindole (adipose stromal cells
      group) or Dulbecco's modified Eagle medium (control group) was transplanted into
      the ischemic myocardium, which was produced by ligation of left descending branch
      of coronary artery. At 1 and 4 weeks after transplantation, specimens were
      acquired from infarcted area and also echocardiography was done to detect the
      effects on heart function. Then, cell morphology and capillary density were
      measured, and vascular endothelial growth factor expression levels were assayed
      by reverse transcription-PCR and enzyme-linked immunosorbent assay. RESULT:
      Adipose stromal cells derived by culture expressed CD44 and CD90 but not CD31 or
      CD45. Adipose stromal cells were alive at 1 and 4 weeks after transplantation and
      had a trend toward differentiation into vascular endothelial cells. The number of
      capillary vessels in peri-infarct area in adipose stromal cells group increased
      significantly compared with control group (P<0.01). The levels of vascular
      endothelial growth factor mRNA and protein expression at 1 week increased
      significantly in adipose stromal cells group compared with control group
      (P<0.01). Left ventricular function, including ejection fraction and fractional
      shortening, was higher in adipose stromal cells group when compared with control
      group at 4 weeks (P<0.01). CONCLUSION: Adipose stromal cells transplantation can
      accelerate angiogenesis in infarcted area after rat myocardial infarction and can
      improve heart function.

PMID- 17429298
TI  - Hemodynamic factors and atheromatic plaque rupture in the coronary arteries: from
      vulnerable plaque to vulnerable coronary segment.
AB  - Coronary plaque disruption with superimposed thrombosis is the underlying
      pathology in the acute coronary syndromes and sudden death. Coronary plaques are
      constantly stressed by a variety of mechanical and hemodynamic forces that may
      precipitate or 'trigger' disruption of vulnerable or, at extreme conditions, even
      stable plaques. This paper reviews the exciting new evidence on the hemodynamic
      factors that may play a role in this process and provides the rationale for the
      introduction of the concept of the vulnerable coronary segment in the study of
      acute coronary syndromes.

PMID- 17429299
TI  - Bibliography of current world literature.

PMID- 17429300
TI  - Radon awareness and mitigation in Vermont: a public health survey.
AB  - Radon exposure is associated with an increased incidence of lung cancer, and
      elevated levels may be found in as many as 1 out of 15 homes. The U.S. EPA
      recommends testing homes for radon and mitigating over the advisory level of 4
      picocuries per liter (4 pCi L(-1), or 148 Bq m(-3)). A sample population from a
      list of Vermont residents who had tested their residence for radon through the
      Vermont Department of Health and who had elevated levels were mailed a survey to
      assess demographic characteristics, knowledge about radon, mitigation rates,
      types of mitigation, as well as barriers to mitigation. The response rate was
      63%. Forty-three percent of respondents mitigated. Roughly half were not
      completely knowledgeable of radon based upon the ability to associate radon
      exposure with lung cancer risk. Reasons not to mitigate radon levels in homes
      were cost and lack of concern over elevated levels. A multivariate logistic
      regression analysis revealed factors associated with mitigating: an education
      level of college or higher (p = 0.02), concern that a high radon level would
      affect real estate value (p = 0.04), and home age less than 10 y (p = 0.05). In
      summary, less than half of Vermonters with elevated radon levels participating in
      the Department of Health program mitigated. We identify factors associated with
      radon mitigation that may lead to improved radon education and mitigation
      practice.

PMID- 17429301
TI  - Occurrence and distribution of 210Pb and 210Po in selected California groundwater
      wells.
AB  - Groundwater wells from across the State of California were sampled and analyzed
      for Pb and Po. The separation method involved Fe(OH)3 precipitation from a 5-L
      groundwater sample followed by electrodeposition of Po on a nickel disk. The
      resulting solution was passed through an ion-exchange resin column for the
      isolation of Pb. De-ionized water spiked at a concentration range from 4.92 mBq
      L(-1) to 755 mBq L(-1) with these radionuclide standards showed excellent
      accuracy and precision of the method. In the groundwater wells, overall activity
      of Pb ranged from 3.7 mBq L(-1) to 1,481 mBq L(-1) and the Po activity ranged
      from 0.25 mBq L(-1) to 555 mBq L(-1). Of the select wells tested, 27% for Pb and
      19% for Po were above the proposed maximum contamination limits for these
      radionuclides, which are set at 37 mBq L(-1) and 26 mBq L(-1), respectively. From
      a public health perspective this is a concern, since the drinking water screening
      levels for gross alpha is at 555 mBq L(-1) and gross beta is at 1,850 mBq L(-1).
      At such high screening levels Pb and Po will not be captured, and this situation
      was found in several of the wells studied. The occurrence of Pb and Po are not
      correlated within the sources, however; the polonium concentrations were always
      lower than the lead concentrations. Activities of Pb measured from wells two
      years apart clearly demonstrated the continuous flux of groundwater within
      aquifers.

PMID- 17429302
TI  - Exposure of the Swiss population by radiodiagnostics: 2003 review.
AB  - A nationwide investigation was conducted in Switzerland to establish the exposure
      of the population by medical x rays and update the results of the 1998 survey.
      Both the frequency and the dose variations were studied in order to determine the
      change in the collective dose. The frequency study addressed 206 general
      practitioners (GPs), 30 hospitals, and 10 private radiology institutes. Except
      for the latter, the response rate was very satisfactory. The dose study relied on
      the assessment of the speed class of the screen-film combinations used by the GPs
      as well as the results of two separate studies dedicated to fluoroscopy and CT.
      The investigation showed that the total number of all medical x-ray examinations
      performed by GPs registered a 1% decrease between 1998 and 2003, and that the
      sensitivities of the film-screen combinations registered a shift towards higher
      values, leading to a reduction of the dose delivered by a GP of the order of 20%.
      The study indicated also that the total number of all x-ray examinations
      performed in hospitals increased by 4%, with a slight increase of radiographies
      by 1% but significant decrease of examinations involving fluoroscopy (39%), and a
      70% increase for CT examinations. Concerning the doses, the investigation of a
      selection of examinations involving fluoroscopy showed a significant increase of
      the kerma-area product (KAP) per procedure. For CT the study showed an increase
      of the dose-length product (DLP) per procedure for skull and abdomen
      examinations, and a decrease for chest examination. Both changes in the frequency
      and the effective dose per examination led to a 20% increase in the total
      collective dose.

PMID- 17429303
TI  - Assessment of the multimedia mitigation of radon in New York.
AB  - Although not yet implemented, the 1996 amendments to the Safe Drinking Water Act
      instructed the states (or local water suppliers) to address radon concentrations
      in community water systems (CWS). As an alternative to reducing waterborne radon
      concentrations in the CWS to the maximum contaminant level (MCL) of 11 Bq L(-1),
      states (or individual CWS) would be permitted to develop a multimedia mitigation
      (MMM) program, which allowed a greater concentration (148 Bq L(-1)) of waterborne
      radon in the CWS, if it could be shown that an equivalent health risk reduction
      could be achieved by reducing indoor radon concentrations. For a MMM program to
      be acceptable, the U.S. Environmental Protection Agency required the health-risk
      reduction attained through mitigations and radon-resistant new construction
      (RRNC) to offset the increased health risk due to radon in community water
      systems above the MCL of 11 Bq L(-1). A quantitative assessment indicates that
      the reduction in health risk currently achieved in New York State through radon
      mitigations and RRNC exceeded the increase in risk associated with an alternative
      MCL of 148 Bq L(-1). The implementation of a MMM program in New York would result
      in an overall reduction in the health risk associated with exposure to radon.

PMID- 17429304
TI  - Tenth value layers for 60Co gamma rays and for 4, 6, 10, 15, and 18 MV x rays in
      concrete for beams of cone angles between 0 degrees and 14 degrees calculated by
      Monte Carlo simulation.
AB  - The calculation of shielding barrier thicknesses for radiation therapy facilities
      according to the NCRP formalism is based on the use of broad beams (that is, the
      maximum possible field sizes). However, in practice, treatment fields used in
      radiation therapy are, on average, less than half the maximum size. Indeed, many
      contemporary treatment techniques call for reduced field sizes to reduce co
      morbidity and the risk of second cancers. Therefore, published tenth value layers
      (TVLs) for shielding materials do not apply to these very small fields. There is,
      hence, a need to determine the TVLs for various beam modalities as a function of
      field size. The attenuation of (60)Co gamma rays and photons of 4, 6, 10, 15, and
      18 MV bremsstrahlung x ray beams by concrete has been studied using the Monte
      Carlo technique (MCNP version 4C2) for beams of half-opening angles of 0 degrees
      , 3 degrees , 6 degrees , 9 degrees , 12 degrees , and 14 degrees . The distance
      between the x-ray source and the distal surface of the shielding wall was fixed
      at 600 cm, a distance that is typical for modern radiation therapy rooms. The
      maximum concrete thickness varied between 76.5 cm and 151.5 cm for (60)Co and 18
      MV x rays, respectively. Detectors were placed at 630 cm, 700 cm, and 800 cm from
      the source. TVLs have been determined down to the third TVL. Energy spectra for
      4, 6, 10, 15, and 18 MV x rays for 10 x 10 cm(2) and 40 x 40 cm(2) field sizes
      were used to generate depth dose curves in water that were compared with
      experimentally measured values.

PMID- 17429305
TI  - Incorporation and distribution of uranium in rats after a contamination on intact
      or wounded skin.
AB  - Uranium uptake can occur accidentally by inhalation, ingestion, injection, or
      absorption through intact or wounded skin. Intact or wounded skin routes of
      absorption of uranium have received little attention. The aims of our work were
      (1) to evaluate the influence of the type of wound contamination on the short
      term distribution and excretion of uranium in rats and (2) to generate data to
      assess the time available to treat contamination of intact or wounded skin before
      significant uptake of uranium occurs. Biokinetic data presented in the present
      paper are based on an in vivo rat model. This study shows that a significant
      uptake of a uranyl nitrate solution through intact skin can occur within the
      first 6 h of exposure. Absorption of a uranyl nitrate solution through excoriated
      skin is significant after only 30 min of exposure. After a 24-h exposure, uranium
      uptake through intact skin and excoriated skin represents about 0.4% and 38% of
      the initial deposit of uranium, respectively. Contaminated serious chemical skin
      burns induced by HNO3 or NaOH are paradoxically less important in terms of
      uranium uptake risk because 99% of the incorporated uranium remains trapped at
      the wound site and its incorporation is delayed for at least 6 h after the
      beginning of contamination. These results confirm that the biokinetics of a given
      physicochemical form of uranium incorporated after wound contamination depend
      largely on the physiological evolution of the considered wound. Each type of
      wound, with its corresponding biokinetics of a uranium species, is a particular
      case.

PMID- 17429306
TI  - Individuals' decisions affecting radiation exposure after a nuclear explosion.
AB  - In the aftermath of a nuclear attack, shelters can offer potentially important
      protection. How well they fill that role depends on a set of interdependent
      decisions made by the individuals and organizations that must prepare and use
      them. We look at three such decisions. For each, we begin with formal analysis of
      the consequences expected from different possible actions. Those analyses are,
      then, reviewed in terms of how individuals facing these choices will perceive
      them, given the information that they are likely to have. The first example
      suggests that preparing a home shelter according to guidelines from the
      Department of Homeland Security may not pass a cost-benefit test. The second
      example explores the use of readily available information about a blast to infer
      how urgently shelter should be sought. The third example considers when shelters
      should be left, suggesting that individuals with the best shelters and slowest
      evacuation speeds should evacuate last, if they have the provisions needed to
      remain. In each case, helping people to protect themselves requires prior risk
      analyses and communication development.

PMID- 17429307
TI  - Seasonality of 214Bi activity in the human body and of 222Rn concentration in
      home ambient air.
AB  - We studied the seasonal variation of the environmental radon progeny (214)Bi
      activity in the whole bodies (WB) of women and men participating in community
      based studies at the Grand Forks Human Nutrition Research Center (GFHNRC), the
      (214)Bi background activity of the GFHNRC whole body counter (WBC) steel room,
      and ambient air (222)Rn concentration in the homes of Grand Forks residents, over
      the 1988-2004 time period. In this cross-sectional epidemiological study, (214)Bi
      activity in women and men, in the WBC steel room, and (222)Rn concentration in
      resident homes fluctuated such that the highest values were observed in winter
      and the lowest in summer, respectively. (214)Bi activity in the WB of human
      subjects was higher in women who have more (214)Bi activity per unit mass than
      men. Apart from their common seasonal pattern, human WB (214)Bi activity (lnBq)
      was comparatively higher than that for the ambient air (222)Rn activity in a
      human-equivalent volume of 72 L.

PMID- 17429308
TI  - Reliability of using 238U/235U and 234U/238U ratios from alpha spectrometry as
      qualitative indicators of enriched uranium contamination.
AB  - Alpha spectrometry is a commonly used technique for the measurement of uranium
      isotopes in environmental samples because it is widely available at a relatively
      low cost. For natural uranium the (234)U to (238)U activity ratio should be 1 and
      the (238)U to (235)U activity ratio should be 21.7. However, a lower (238)U to
      (235)U ratio is usually observed in alpha spectrometric analysis of environmental
      soil samples. This observation has led to the conclusion that soils from nuclear
      weapons facilities were contaminated with highly enriched uranium. This study was
      undertaken to test the reliability of using activity ratios from alpha
      spectrometry to infer the presence of highly enriched uranium in soil samples.
      The results of these experiments indicate that the (238)U to (235)U activity
      ratio is not a reliable indicator, but that the (234)U to (238)U activity ratio
      can be used to qualitatively indicate the presence of highly enriched uranium at
      concentrations near 10 ng g(-1) and above.

PMID- 17429312
TI  - Effect of CYP2D6 metabolizer status on the disposition of the (+) and (-)
      enantiomers of perhexiline in patients with myocardial ischaemia.
AB  - AIMS: This study investigated the effects of increasing doses of rac-perhexiline
      maleate and CYP2D6 phenotype and genotype on the pharmacokinetics of (+) and (-)
      perhexiline. METHODS: In a prospective study, steady-state plasma concentrations
      of (+) and (-)-perhexiline were quantified in 10 CYP2D6 genotyped patients
      following dosing with 100 mg/day rac-perhexiline maleate, and following a
      subsequent dosage increase to 150 or 200 mg/day. In a retrospective study, steady
      state plasma concentrations of (+) and (-)-perhexiline were obtained from 111
      CYP2D6 phenotyped patients receiving rac-perhexiline maleate. RESULTS: In the
      prospective study, comprising one poor and nine extensive/intermediate
      metabolizers, the apparent oral clearance (CL/F) of both enantiomers increased
      with the number of functional CYP2D6 genes. In the nine extensive/intermediate
      metabolizers receiving the 100 mg/day dose, the median CL/F of (+)-perhexiline
      was lower than that of (-)-perhexiline (352.5 versus 440.6 l/day, P<0.01).
      Following the dosage increase, the median CL/F of both enantiomers decreased by
      45.4 and 41.4%, respectively. In the retrospective study, the median (+)-/(-)
      perhexiline plasma concentration ratio was lower (P<0.0001) in phenotypic
      extensive/intermediate (1.41) versus poor metabolizers (2.29). Median CL/F of (+)
      and (-)-perhexiline was 10.6 and 24.2 l/day (P<0.05), respectively, in poor
      metabolizers, and 184.1 and 272.0 l/day (P<0.001), respectively, in
      extensive/intermediate metabolizers. CONCLUSIONS: Perhexiline's pharmacokinetics
      exhibit significant enantioselectivity in CYP2D6 extensive/intermediate and poor
      metabolizers, with both enantiomers displaying polymorphic and saturable
      metabolism via CYP2D6. Clinical use of rac-perhexiline may be improved by
      developing specific enantiomer target plasma concentration ranges.

PMID- 17429313
TI  - Intron 1 CA dinucleotide repeat polymorphism and mutations of epidermal growth
      factor receptor and gefitinib responsiveness in non-small-cell lung cancer.
AB  - OBJECTIVE: Limited availability of tumoral tissue in non-small-cell lung cancer
      and presence of epidermal growth factor receptor mutation-independent responses
      call for investigation of other molecular predictive marker of gefitinib
      responsiveness. Therefore, CA repeat polymorphism in intron 1 was analyzed for
      its association with gefitinib responsiveness together with epidermal growth
      factor receptor mutation in Korean patients. PATIENTS AND METHODS: For 86
      advanced non-small-cell lung cancer patients treated with gefitinib, epidermal
      growth factor receptor mutation was analyzed by direct sequencing (exons 18-21)
      from tumor tissue and CA repeat polymorphism was assessed by fragment length
      analysis from tumor and/or normal tissue. RESULTS: CA repeat status was identical
      in 33 patients with matched tumor and normal tissue. CA repeat was low (sum of
      both alleles < or =37) in 40 (46.5%) and high (sum > or =38) in 46 (53.5%)
      patients. Although epidermal growth factor receptor mutation was more frequent in
      high CA repeat patients [17.5% (7/40) in low vs. 28.3% (13/46) in high, P=0.18],
      response rate was higher in low CA repeat patients [25.0% (10/40) in low vs.
      13.0% (6/46) in high, P=0.16]. In multivariate analysis, low CA repeat was
      associated with better objective response (odds ratio 7.1, 95% confidence
      interval 1.2-40.8; P=0.029) and time-to-progression (hazard ratio 0.54, 95%
      confidence interval 0.34-0.88; P=0.014), independent of the epidermal growth
      factor receptor mutational status. CA repeat status was not associated with
      epidermal growth factor receptor expression. CONCLUSION: Low number of CA repeats
      in intron 1 of epidermal growth factor receptor is associated with gefitinib
      responsiveness in non-small-cell lung cancer patients independent of epidermal
      growth factor receptor mutation.

PMID- 17429314
TI  - Influence of the UGT2B7 promoter region and exon 2 polymorphisms and
      comedications on Acyl-MPAG production in vitro and in adult renal transplant
      patients.
AB  - INTRODUCTION: The polymorphic enzyme UGT2B7 metabolizes mycophenolic acid into
      acyl-mycophenolic acid-glucuronide (AcMPAG), a presumably toxic metabolite. This
      study aimed at investigating in vitro and in vivo the impact on AcMPAG production
      of: (i) the UGT2B7 gene G-842A single nucleotide polymorphism, in complete
      linkage disequilibrium with most other known single nucleotide polymorphisms in
      the promoter region of this gene and with the C802T single nucleotide
      polymorphism in exon 2 (UGT2B*2); and (ii) of the other immunosuppressants given
      to renal transplant patients in association with mycophenolate mofetil. METHODS:
      We compared the production of AcMPAG by human liver microsomes genotyped for the
      UGT2B7 G-842A and C802T single nucleotide polymorphisms, and plasma AcMPAG
      concentrations in genotyped renal transplant patients administered mycophenolate
      mofetil associated with sirolimus (n=40), tacrolimus (n=24) or cyclosporin (n=28)
      and decreasing doses of corticosteroids, over the first 3 months after
      transplant. The effect of corticosteroids was also investigated in vitro using
      rats' liver microsomes. RESULTS: The two polymorphisms studied were in complete
      reverse linkage disequilibrium. AcMPAG production was 1.25 and 1.56-fold higher
      in G-842A and -842AA human liver microsomes, respectively, compared with GG-842
      human liver microsomes (P=0.01). Enzyme kinetics showed 1.4 and 3.7-fold higher
      Vmax in the respective pools of human liver microsomes. Km values were 0.20, 0.25
      and 0.44 mmol/l for the GG-842, G-842A and -842AA genotypes, respectively. This
      clear increase in Vmax is in favor of the implication of the promoter region
      polymorphisms, whereas the slighter increase in Km might be due to the UGT2B7*2
      single nucleotide polymorphism. Consistently, the UGT2B7 genotype significantly
      influenced AcMPAG area under the curve (AUC0-9 h)/dose in patients on sirolimus
      at months 1 and 3 after transplant (P=0.04 for both). No effect was observed in
      patients on tacrolimus and possibly also on cyclosporin, maybe owing to
      pharmacokinetic interaction with mycophenolate. AcMPAG production was increased
      in corticosteroid-induced rat liver microsomes, consistent with the observed in
      vivo decrease of mycophenolic acid metabolites AUC0-9 h/dose with time after
      transplant. CONCLUSION: Both UGT2B7 polymorphisms and co-medications
      significantly influenced AcMPAG production, but cyclosporin and tacrolimus
      hindered the phenotypic impact of this trait.

PMID- 17429315
TI  - Genetic polymorphisms in estrogen-metabolizing genes and breast cancer survival.
AB  - BACKGROUND: Estrogen plays a central role in the development and progression of
      breast cancer. The estrogen's effects are at least partially regulated by
      estrogen-metabolizing enzymes. The objective of the study is to investigate
      associations of breast cancer survival with genetic polymorphisms in several
      genes involved in estrogen metabolism (CYP1A1, CYP1A2, CYP1B1, COMT, and AhR).
      METHODS: A cohort of 1140 patients aged between 25 and 64 years at the time of
      diagnosis for primary breast cancer during 1996-1998 were included in the study.
      Patients were followed for cancer recurrence and mortality through July 2005.
      RESULTS: Associations were observed at rs4680 (Met158Val) in the COMT gene and
      rs4646903 (CYP1A1*2A) in the CYP1A1 gene. The adjusted hazard ratio for the
      rs4680 AA genotype (low enzyme activity genotype) was 1.6 (95% confidence
      interval, 1.1-2.4) compared with the GG genotype for disease-free survival.
      Adjusted hazard ratios for the rs4646903 CC genotype were 1.6 (95% confidence
      interval, 1.2-2.2) for disease-free survival and 1.4 (95% confidence interval,
      1.0-2.1) for overall survival compared with the TT genotype. No apparent
      association was found for any of the other six single nucleotide polymorphisms
      evaluated in the AhR, CYP1A1, CYP1A2, and CYP1B1 genes. CONCLUSION: Results from
      this study suggest that rs4680 in the COMT gene and rs4646903 in the CYP1A1 gene
      may be genetic markers for breast cancer prognosis in Chinese women.

PMID- 17429316
TI  - CYP2D6 genotype in relation to perphenazine concentration and pituitary
      pharmacodynamic tissue sensitivity in Asians: CYP2D6-serotonin-dopamine crosstalk
      revisited.
AB  - OBJECTIVES: Hyperprolactinemia is a common side effect of first-generation
      antipsychotics mediated by antagonism of dopaminergic neurotransmission in the
      pituitary. Most first-generation antipsychotics are metabolized by CYP2D6 in the
      liver. Further, CYP2D6 is expressed in the human brain as a 5
      methoxyindolethylamine O-demethylase potentially contributing to regeneration of
      serotonin from 5-methoxytryptamine. As dopaminergic neurotransmission is subject
      to regulation by serotonin, CYP2D6 may exert a nuanced (serotonergic) influence
      on dopaminergic tone in the pituitary. CYP2D6*10 is an allele associated with
      reduced enzyme function and occurs in high frequency (about 50%) in Asians. We
      prospectively evaluated significance of CYP2D6 genetic variation for prolactin
      response to perphenazine (a model first-generation antipsychotic) in Asians.
      METHODS: A single oral dose of perphenazine (0.1 mg/kg) or placebo was
      administered to 22 medication-free nonsmoker healthy male Chinese-Canadian
      volunteers, following a double-blind within-subject randomized design. Blood
      samples were drawn at baseline and 2, 3, 4, 5 and 6 h after drug administration.
      RESULTS: In volunteers with CYP2D6*10/CYP2D6*10 genotype, the mean area under
      curve (AUC0-6) for perphenazine concentration was 2.9-fold higher than those who
      carry the CYP2D6*1 allele (P<0.01). Notably, volunteers homozygous for CYP2D6*10
      exhibited a significant reduction (66%) in mean pharmacodynamic tissue
      sensitivity as measured by the (prolactin-AUC0-6/perphenazine-AUC0-6) ratio
      (P=0.02). CONCLUSIONS: CYP2D6 genotype is a significant contributor to
      perphenazine concentration in Chinese-Canadians. Importantly, prolactin response,
      when normalized per unit perphenazine concentration, appears to be blunted in
      volunteers homozygous for CYP2D6*10. We suggest that CYP2D6 genetic variation may
      potentially influence pharmacodynamic tissue sensitivity in the pituitary,
      presumably through disposition of an endogenous substrate (e.g. 5
      methoxytryptamine).

PMID- 17429317
TI  - CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: the
      Atherosclerosis Risk in Communities (ARIC) study.
AB  - OBJECTIVE: The cytochromes P450 epoxygenases CYP2J2 and CYP2C8 synthesize
      epoxyeicosatrienoic acids, which regulate endothelial function. We sought to
      determine if genetic variation in CYP2J2 and CYP2C8 was associated with coronary
      heart disease risk. METHODS: We genotyped 2065 Atherosclerosis Risk in
      Communities study participants (1085 incident coronary heart disease cases, 980
      noncases) for polymorphisms in CYP2J2 and CYP2C8. Using a case-cohort design,
      associations between genotype and incident coronary heart disease risk were
      evaluated using proportional hazards regression. The influence of cigarette
      smoking on these associations was also evaluated. False discovery rate q-values
      were estimated to minimize the impact of the multiple statistical comparisons
      completed. All analyses were race stratified. RESULTS: The CYP2J2 G-50T
      polymorphism variant -50T allele was associated with significantly lower risk of
      incident coronary heart disease in African-Americans (adjusted hazard rate ratio
      0.58, 95% confidence interval 0.35-0.96, P=0.036, q=0.051); however, no
      significant association was observed in Caucasians. Overall, the I264M, I269F,
      and K399R polymorphisms in CYP2C8 were not significantly associated with risk of
      incident coronary heart disease. In Caucasians, the relationship between the
      I264M and K399R polymorphisms and incident coronary heart disease risk was
      significantly modified by cigarette smoking status (P for interaction=0.008,
      q=0.064), with the highest risk observed in smokers carrying at least one variant
      allele. CONCLUSIONS: The G-50T polymorphism in CYP2J2 may be an important risk
      factor for the development of coronary heart disease events in African-Americans,
      whereas cigarette smoking may modify the relationship between the I264M and K399R
      polymorphisms in CYP2C8 and coronary heart disease risk in Caucasians.
      Confirmation of these findings in an independent population is warranted.

PMID- 17429318
TI  - Cost-effectiveness of pharmacogenetic testing to predict treatment response to
      angiotensin-converting enzyme inhibitor.
AB  - OBJECTIVE: This study aimed to assess the potential cost-effectiveness of testing
      patients with nephropathies for the I/D polymorphism before starting angiotensin
      converting enzyme (ACE) inhibitor therapy, using a 3-year time horizon and a
      healthcare perspective. METHODS: We used a combination of a decision analysis and
      Markov modeling technique to evaluate the potential economic value of this
      pharmacogenetic test by preventing unfavorable treatment in patients with
      nephropathies. The estimation of the predictive value of the I/D polymorphism is
      based on a systematic review showing that DD carriers tend to respond well to ACE
      inhibitors, while II carriers seem not to benefit adequately from this treatment.
      Data on the ACE inhibitor effectiveness in nephropathy were derived from the REIN
      (Ramipril Efficacy in Nephropathy) trial. We calculated the number of patients
      with end-stage renal disease (ESRD) prevented and the differences in the
      incremental costs and incremental effect expressed as life-years free of ESRD. A
      probabilistic sensitivity analysis was conducted to determine the robustness of
      the results. RESULTS: Compared with unselective treatment, testing patients for
      their ACE genotype could save 12 patients per 1000 from developing ESRD during
      the 3 years covered by the model. As the mean net cost savings was euro 356,000
      per 1000 patient-years, and 9 life-years free of ESRD were gained, selective
      treatment seems to be dominant. CONCLUSION: The study suggests that genetic
      testing of the I/D polymorphism in patients with nephropathy before initiating
      ACE therapy will most likely be cost-effective, even if the risk for II carriers
      to develop ESRD when treated with ACE inhibitors is only 1.4% higher than for DD
      carriers. Further studies, however, are required to corroborate the difference in
      treatment response between ACE genotypes, before genetic testing can be justified
      in clinical practice.

PMID- 17429319
TI  - Pregnane X receptor polymorphism affects CYP3A4 induction via a ligand-dependent
      interaction with steroid receptor coactivator-1.
AB  - BACKGROUND: The human pregnane X receptor is a ligand-dependent transcription
      factor that plays critical roles in regulating detoxification genes such as
      CYP3A4 by recruiting transcriptional coactivators such as steroid receptor
      coactivator-1 in a ligand-dependent manner. In a previous study (Pharmacogenetics
      and Genomics 2005, 15: 337-341), we reported a novel pregnane X receptor single
      nucleotide polymorphism, Q158K, which impaired transactivation of CYP3A4. METHODS
      AND RESULTS: By using DNA affinity precipitation assay and electrophoretic
      mobility shift assay, we have now shown that Q158K does not alter the binding
      affinity of pregnane X receptor for the CYP3A4 promoter. Instead, as shown using
      a mammalian two-hybrid assay, it decreased the interaction of pregnane X receptor
      with steroid receptor coactivator-1 in the presence of rifampin, clotrimazole,
      paclitaxel, or nifedipine but not in their absence. Rifampin treatment markedly
      increased pregnane X receptor protein in the wild-type pregnane X receptor
      transfected cells as shown by coimmunoprecipitation but not in Q158K pregnane X
      receptor-transfected cells. The impaired transactivation of the CYP3A4 promoter
      was reversed by transfecting steroid receptor coactivator-1 expression plasmids.
      An additional nine pregnane X receptor variants were isolated and selected by
      random mutagenesis. Mutations Q158, W223, F257, I346, and L424 also reduced
      CYP3A4 transactivation and interaction in mammalian two-hybrid assays only in the
      presence of ligands. Although Q158K did not greatly affect the interaction of
      pregnane X receptor to silencing mediator of retinoid and thyroid hormone
      receptor, pregnane X receptor-silencing mediator of retinoid and thyroid hormone
      receptor interaction was impaired in the F257L and I346T variants with or without
      the presence of pregnane X receptor ligands. CONCLUSION: Our data indicate that
      the impaired induction by the Q158K variant is probably due to defective steroid
      receptor coactivator-1 interaction in the presence of a pregnane X receptor
      ligand. As the whole ligand binding domain of pregnane X receptor is required for
      the interaction with steroid receptor coactivator-1, we propose that, not only
      the Q158K variant found in Chinese, but also in native pregnane X receptor
      variants in other ethnic groups (D163G, A370T, R381W, and I403V) affect CYP3A4
      induction by altering steroid receptor coactivator-1 recruitment.

PMID- 17429320
TI  - Ureteric injury caused by a penetrating arrow.

PMID- 17429321
TI  - Para-aortic retained bullet causing aortic thrombosis: a case report.

PMID- 17429323
TI  - Delayed presentation of posttraumatic internal pudendal artery-urethral fistula
      treated by selective embolization.

PMID- 17429324
TI  - Penetrating thoracic injuries: the use of transesophageal echocardiography to
      monitor for complications after intracardiac nail removal.

PMID- 17429325
TI  - Successful management of a trauma patient with pulmonary hemorrhage using a wire
      guided bronchial blocker.

PMID- 17429326
TI  - Successful management of pediatric cardiac contusion with extracorporeal membrane
      oxygenation.

PMID- 17429327
TI  - Arteriovenous extracorporeal lung assist and high frequency oscillatory
      ventilation in post-traumatic acute respiratory distress syndrome.

PMID- 17429328
TI  - Traumatic forequarter amputation complicated with transient horner syndrome: case
      report.

PMID- 17429329
TI  - Hernia development after traumatic injury to the pelvic ilium: case report and
      novel approach to repair.

PMID- 17429330
TI  - A case of asystole from periorbital laceration manipulation and oculocardiac
      reflex in an acute trauma setting.

PMID- 17429331
TI  - Hemodynamic instability following an avulsion of the corona mortis artery
      secondary to a benign pubic ramus fracture.

PMID- 17429332
TI  - Comparison of transvaginal ultrasonography and saline infusion sonohysterography
      in evaluating the endometrial cavity in pre- and postmenopausal women with
      abnormal uterine bleeding.
AB  - OBJECTIVE: To compare the diagnostic accuracy of transvaginal ultrasonography
      (TVUS) and saline infusion sonohysterography (SIS) of the endometrial cavity in
      pre- and postmenopausal women with abnormal uterine bleeding. DESIGN: In a
      prospective study, TVUS and concurrent SIS findings of 100 pre- and 33
      postmenopausal women were recorded. The pathological diagnoses of the specimens,
      obtained by means of dilatation and curettage, hysteroscopy, and hysterectomy,
      were taken as reference and compared with the results of TVUS and SIS. RESULTS:
      When TVUS and SIS findings were compared with pathological results, the
      sensitivity and specificity of TVUS in diagnosing endometrial pathologies were
      83% and 70.6%, respectively, whereas the sensitivity and specificity of SIS were
      97.7% and 82.4%, respectively. The sensitivity and specificity of SIS in the
      diagnosis of endometrial polyps were 100% and 91.8%, respectively, and in the
      diagnosis of fibroids were 95% and 100%, respectively. CONCLUSION: SIS is more
      accurate than TVUS alone in the evaluation of the endometrial cavity in women
      with abnormal uterine bleeding.

PMID- 17429333
TI  - Does menopausal transition affect the quality of life? A longitudinal study of
      middle-aged women in Kinmen.
AB  - OBJECTIVE: The aim of this study was to investigate the role of menopausal
      transition and menopausal symptoms in relation to quality of life in a cohort of
      middle-aged women in Kinmen. DESIGN: A total of 734 premenopausal women
      participated in the baseline study, and 579 women (78.9%) completed a follow-up 2
      years later. Quality of life was assessed by the Medical Outcomes Study Short
      Form-36. Participating women were asked for demographic data, about vasomotor
      symptoms, and to complete the Medical Outcomes Study Short Form-36 and the
      Hospital Anxiety and Depression Scale. RESULTS: There was no demographic
      difference between women who remained premenopausal and those who entered
      perimenopause except for age. Vitality deteriorated no matter whether the women
      stayed in premenopause or entered perimenopause. In multivariate analysis, only
      vasomotor symptoms had an adverse influence on role limitation of emotion after
      adjusting for age, education, menopausal status, baseline cognitive score, and
      Hospital Anxiety and Depression Scale score. The menopausal transition did not
      influence the eight domains of the Short Form-36 in the multivariate regression
      model. CONCLUSION: This longitudinal study found no significant effect of
      menopausal transition on quality of life among Taiwanese women. The decline in
      the role limitations due to emotional problems was related to vasomotor symptoms.

PMID- 17429334
TI  - Women's awareness and knowledge of hormone therapy post-Women's Health
      Initiative.
AB  - OBJECTIVE: Findings from the Women's Health Initiative (WHI) failed to confirm
      previous expectations about the net benefits of menopausal hormone therapy and
      have resulted in reduced use of these medications. The aim of this study was to
      evaluate women's awareness and knowledge concerning the risks and benefits of
      hormone therapy. DESIGN: A nationally representative survey was completed for a
      sample of 781 women (ages 40-60 y, mean 49 y) drawn from the Knowledge Networks
      Internet panel 24 months after publication of the first WHI findings, in June
      2004. Responses were weighted to reflect the demographics of the US population.
      The main outcome measures were awareness of WHI and knowledge of its findings. An
      aggregate score was constructed to assess women's knowledge of the impact of
      hormone therapy on seven key disease outcomes. Logistic regression determined the
      independent predictors of (1) WHI awareness and (2) a positive aggregate
      knowledge score, reflecting appropriate responses about risks and benefits.
      RESULTS: Only 29% of women were aware of the WHI results. Only 40% of women had a
      positive aggregate knowledge score. Aside from awareness of WHI and independent
      of other factors, knowledge scores were lower for African American women (odds
      ratio, 0.4; 95% CI: 0.2-0.6) and among women with less education (odds ratio,
      0.5; 95% CI: 0.3-0.9). Knowledge was greatest for breast cancer and osteoporosis
      outcomes and most limited for colorectal cancer and memory loss. CONCLUSION:
      Surveyed women had limited awareness and knowledge of the WHI results, suggesting
      limited diffusion. Targeting younger, less educated, and African American women
      is warranted.

PMID- 17429335
TI  - Difference in segmental lean and fat mass components between pre- and
      postmenopausal women.
AB  - OBJECTIVE: To investigate the differences in segmental body composition (lean and
      fat mass components) between pre- and postmenopausal women. DESIGN: Participants
      were 413 premenopausal women aged 20 to 53 years old and 229 postmenopausal women
      aged 50 to 75 years old with right-side dominance. Age, height, weight, body mass
      index, age at menopause, and years since menopause were recorded. The percentages
      of fat mass in the arms, trunk, legs, and total body were measured by dual-energy
      x-ray absorptiometry. The ratio of trunk to leg fat mass (trunk-leg fat mass
      ratio) was also measured by dual-energy x-ray absorptiometry. RESULTS: The
      percentage of trunk fat mass and the trunk-leg fat mass ratio were significantly
      higher in postmenopausal women, but the percentages of leg fat mass did not
      differ. In the two groups, percentage of trunk fat mass and trunk-leg fat mass
      ratio were similarly and positively correlated with age. However, percentage of
      leg fat mass did not correlate with age. The percentage of fat mass at each
      segmental site and the trunk-leg fat mass ratio did not differ between
      premenopausal women aged 50 to 53 years old (n=52) and age-matched postmenopausal
      women (n=43, years since menopause=2.8+/-1.8). CONCLUSIONS: Aging rather than
      menopause contributes to the increase in the percentage of trunk fat mass.
      However, the percentage of leg fat mass does not change with aging. Upper body
      fat distribution in postmenopausal women may be more attributable to aging than
      to menopause.

PMID- 17429337
TI  - Structural and functional properties of the healed tympanic membrane: a long-term
      follow-up after laser myringotomy.
AB  - HYPOTHESIS: The short-term healing scar that forms after experimental laser
      myringotomy will revert to a normal lamina propria in the long run. The
      mechanical stiffness will stay normal. BACKGROUND: Recent studies have shown
      severe structural changes in the fibrous layer in the early course after
      experimental laser myringotomy, whereas the scar quickly restored the strength of
      the tympanic membrane (TM). A reorganization of the fiber layer is expected to
      occur. METHODS: Potassium titanyl phosphate laser myringotomy was made on one
      side of the TM in Sprague-Dawley rats. The ear of the other side was untouched
      and used for control. After half a year of observation, the stiffness and
      strength of the healed TMs were measured with moire interferometry and examined
      with otomicroscopy and light and electron microscopy. RESULTS: The interferometry
      readings showed a slightly reduced strength in the myringotomized and healed TMs.
      After half a year, still there were immense structural changes including
      increased thickness over a wide area of the pars tensa with increased amounts of
      fibers. An obvious reorganization of the fiber layer was lacking. CONCLUSION:
      Laser myringotomy causes profound, long-standing, or permanent structural changes
      in the lamina propria of the pars tensa, whereas the strength of the TM may
      become slightly reduced.

PMID- 17429338
TI  - Erythropoietin and erythropoietin receptor expression in vestibular schwannoma:
      potential role in tumor progression.
AB  - HYPOTHESIS: Hypoxia-inducible factor (HIF)-1alpha, erythropoietin (Epo), Epo
      receptor (EpoR), and bcl-2 are expressed in both sporadic unilateral vestibular
      schwannomas (VSs) and those associated with neurofibromatosis Type 2, and the
      expression data correlate with clinicopathological tumor features including
      microvessel density and Ki-67-labeling index. BACKGROUND: Erythropoietin
      expression is regulated by the transcription factor, HIF-1alpha. Erythropoietin
      signaling via EpoR results in stimulation of cell proliferation and elevated
      expression of the antiapoptotic protein, bcl-2, and then inhibition of apoptosis.
      Erythropoietin has been shown to be associated with Schwann cell proliferation,
      and a recent report suggested a role in VS growth. METHODS: Immunohistochemical
      analysis of HIF-1alpha, Epo, EpoR, and bcl-2 was performed on formalin-fixed
      paraffin-embedded archival surgical specimens. Microvessel density and Ki-67
      labeling index of VS were analyzed and correlated with the immunoreactivity
      pattern of the examined factors. RESULTS: Immunoreactivity data demonstrate
      robust protein expression for HIF-1alpha, Epo, EpoR, and bcl-2 in VS. Sixty-six
      percent of the cases showed Epo expression, and EpoR was found in 85% of tumor
      samples. A significantly positive correlation of the immunoreactivity scores of
      Epo/EpoR and bcl-2 expression could be noted. In case of tumor specimens with
      high levels of HIF-1alpha expression, a significantly higher Ki-67-labeling index
      was observed. There was no correlation between the expression of HIF-1alpha, Epo,
      EpoR, and bcl-2 and microvessel density, tumor size, sex, and age. CONCLUSION:
      Expression of Epo and EpoR might suggest a functional role in VS biology. The
      observed correlation of Epo/EpoR and bcl-2 expression levels may suggest a
      proliferative and antiapoptotic role of the Epo/EpoR system in VS.

PMID- 17429339
TI  - Nestin expression in the kidney with an obstructed ureter.
AB  - Nestin is an intermediate filament protein originally identified in
      neuroepithelial stem cells. This cytoskeletal-associated protein is also
      expressed in some non-neuronal organs including renal tubular cells and
      glomerular endothelial cells during kidney development. Little is known, however,
      about nestin expression in the kidney during injury. In this study, we find
      nestin expression induced in renal tubular and interstitial myofibroblasts in the
      adult rat kidney following unilateral ureteral obstruction. The degree of nestin
      expression was well correlated with the degree of tubulointerstitial fibrosis.
      Immunohistochemical identification of specific nephron segments showed that
      nestin was primarily expressed by proximal tubules, partially by distal tubules
      and thick ascending limbs of Henle but not by collecting ducts. The nestin
      positive tubular cells also expressed vimentin and heat-shock protein 47 (HSP47)
      suggesting these cells reverted to a mesenchymal phenotype. Not all vimentin- or
      HSP-expressing cells expressed nestin; however, suggesting that nestin is
      distinct from these conventional mesenchymal markers. Nestin expression was also
      found associated with phenotypical changes in cultured renal cells induced by
      hypoxia or transforming growth factor-beta. Nestin expression was located in
      hypoxic regions of the kidney with an obstructed ureter. Our results indicate
      that nestin could be a novel marker for tubulointerstitial injury.

PMID- 17429341
TI  - Proposed mechanisms in renal tubular crystal retention.
AB  - The production of concentrated urine inevitably leads to the precipitation of
      poorly soluble waste salts in the renal tubular fluid. These crystallization
      processes are physiologic and without consequences as long as all crystals are
      excreted with the urine. The retention of crystals in the renal tubules, however,
      may lead to tubular nephrocalcinosis. Here, we present a brief survey of the
      possible mechanisms involved in this process, which seems to depend predominantly
      on the presence of regenerating/(re)differentiating cells in the renal tubules.
      Crystal binding to the surface of these cells can be mediated by a number of
      luminal membrane molecules, including acidic fragment of nucleolin-related
      protein, annexin-II, osteopontin, and hyaluronan.

PMID- 17429340
TI  - Hypertension and impaired renal function accompany juvenile obesity: the effect
      of prenatal diet.
AB  - Obesity has been suggested to have a detrimental impact on kidney structure and
      function, leading to focal glomerulosclerosis and hypertension. It is also
      associated with hyperleptinemia and elevated renal sympathetic nerve activity.
      Prenatal undernutrition promotes postnatal obesity, hypertension, and an altered
      renal structure and function. In this study, we examined the effects of prenatal
      nutrient restriction and juvenile obesity in sheep. We found that juvenile
      obesity led to chronic hyperleptinemia and reduced renal function as assessed by
      nuclear scintigraphy. Additional factors include hypertension,
      glomerulosclerosis, and increased kidney apoptosis. Prenatal undernutrition,
      synchronous with early kidney development, coupled postnatally with juvenile
      obesity had no effect on systemic pathophysiological sequalae associated with
      obesity per se. Hypertension, hyperleptinemia, and poor renal function were all
      observed in this group. All indices of renal pathology such as increased
      expression of proinflammatory cytokines, angiotensin II, glucocorticoid
      receptors, and increased apoptosis and glomerulosclerosis were entirely absent in
      obese prenatally undernourished offspring. Our data indicate that juvenile
      obesity per se leads to systemic hypertension and renal structural and functional
      pathology. Prenatal undernutrition effectively abolishes any renal histopathology
      associated with juvenile obesity.

PMID- 17429342
TI  - Modulation of angiotensin II and norepinephrine-induced plasminogen activator
      inhibitor-1 expression by AT1a receptor deficiency.
AB  - Angiotensin (Ang) II stimulates plasminogen activator inhibitor-1 (PAI-1)
      expression in many cell types by mechanisms that are cell-type specific. We
      measured effects of Ang II or norepinephrine on PAI-1 expression in wild type
      (WT) and Ang type-1a receptor knockout mice (AT(1a)-/-) in the presence or
      absence of the non-specific AT(1) antagonist losartan. Ang II and norepinephrine
      increased systolic blood pressure equally, whereas losartan decreased the pressor
      response of the former but not the latter in WT mice. In AT(1a)-/- mice, baseline
      systolic blood pressure was lower with no effect of Ang II, norepinephrine, or
      losartan. Ang II stimulated PAI-1 expression in the heart, aorta, and kidney and
      markedly in the liver of WT mice. In AT(1a)-/- mice, Ang II-stimulated PAI-1 was
      significantly attenuated compared with the WT in the heart and aorta but
      significantly enhanced in the kidney. Losartan decreased the induction in the
      aorta and liver of WT, and in the kidney and liver of AT(1a)-/- mice.
      Norepinephrine increased PAI-1 expression in WT heart and aorta, and in AT(1a)-/-
      heart, kidney, and liver with no effect of losartan. Renal PAI-1 expression
      correlated with AT(1b) receptor mRNA. We conclude that Ang II stimulates PAI-1
      expression in part through the AT(1b) receptor in the kidney and liver. Further,
      norepinephrine induces PAI-1 expression in vivo with AT(1a) receptor deficiency
      modulating the effect.

PMID- 17429343
TI  - Microinflammation induces endothelial damage in hemodialysis patients: the role
      of convective transport.
AB  - Cardiovascular complications are a major cause of mortality in hemodialysis
      patients. On-line hemofiltration combines convective clearance for removing large
      solutes with diffusion to remove small solutes and is associated with a
      significant reduction of inflammation and improved patient survival. We compared
      on-line hemofiltration to high-flux hemodialysis (HF-HD) in patients in a
      sequential manner. At baseline, 15 stable patients on HF-HD as compared with five
      control subjects showed significant increases in CD14+CD16+ cells, endothelial
      microparticles, and endothelial progenitor cells (EPCs). After 4 months of on
      line hemofiltration, the number of CD14+CD16+ cells, microparticles, and EPCs
      decreased. After returning to HF-HD for 4 months, all measured parameters
      returned to their respective baseline values. The number of CD14+CD16+ cells
      correlated with both endothelial microparticles and EPCs. We conclude that on
      line hemofiltration attenuates endothelial dysfunction possibly by decreasing
      microinflammation. This effect may be directly caused by a modulatory effect of
      on-line hemofiltration on proinflammatory cells or by a complex interaction that
      encompasses a wider removal of uremic toxins.

PMID- 17429345
TI  - Uremic pruritus.

PMID- 17429344
TI  - Renal tubule necrosis and apoptosis modulation by A1 adenosine receptor
      expression.
AB  - We have shown that A1 adenosine receptors (A1ARs) are cytoprotective against
      renal tubular necrosis and apoptosis both in vivo and in vitro. To study the role
      of A1AR numbers on renal epithelial cell survival, we stably overexpressed the
      human A1 receptor in a porcine renal tubule cell line and utilized primary
      cultures of proximal tubules obtained from A1AR knockout mice. Receptor
      overexpressing cells were protected against peroxide-induced necrosis and tumor
      necrosis factor-alpha/cycloheximide-induced apoptosis. Conversely, cultured
      proximal tubule cells from receptor knockout mice showed more necrotic and
      apoptotic cell loss than corresponding cells from wild-type mice. Overexpression
      of the receptor resulted in a significantly higher baseline expression of both
      total and phosphorylated heat-shock protein (HSP)27; the latter due to A1
      receptor enhancement of p38 and AP2 mitogen-activated protein kinase activities.
      The resistance to cell death in the porcine cells was reversed by selective A1
      receptor antagonism and by a selective inhibitor of HSP synthesis. Receptor
      activation in wild-type mice in vivo led to increased total and phosphorylated
      HSP27, whereas receptor knockout mice showed decreased baseline and adenosine
      mediated HSP phosphorylation. These studies show that endogenous A1AR activation
      produces cytoprotective effects in renal proximal tubules by modulating HSP27
      signaling pathways.

PMID- 17429346
TI  - Transient cooling during early reperfusion attenuates delayed edema and infarct
      progression in the Spontaneously Hypertensive Rat. Distribution and time course
      of regional brain temperature change in a model of postischemic hypothermic
      protection.
AB  - The temperature threshold for protection by brief postischemic cooling was
      evaluated in a model of transient focal ischemia in the Spontaneously
      Hypertensive Rat, using an array of epidural probes to monitor regional brain
      temperatures. Rats were subjected to 90 mins tandem occlusion of the right middle
      cerebral artery (MCA) and common carotid artery. Systemic cooling to 32 degrees C
      was initiated 5 mins before recirculation, with simultaneous brain cooling to
      temperatures ranging from 28 degrees C to 32 degrees C within the MCA territory
      by means of a temperature-controlled saline drip. Rewarming was initiated at 2 h
      recirculation and was complete within 30 mins. Tissue damage and edema volume
      showed clear temperature-dependent reductions when evaluated at 3 days survival,
      with no protection evident in the group at 32 degrees C but progressive effects
      on both parameters after deeper cooling. A particularly striking effect was the
      essentially complete elimination of edema progression between 1 and 3 days.
      Temperature at distal sites within the MCA territory better predicted reductions
      in lesion volume, indicating that protection required effective cooling of the
      penumbral regions destined to be spared. These results show that even brief
      cooling can be highly protective when initiated at the time of recirculation
      after focal ischemia, but indicate a substantially lower temperature threshold
      for hypothermic protection than has been reported for other strains, occlusion
      methods, and cooling durations.

PMID- 17429347
TI  - Nox2-derived reactive oxygen species mediate neurovascular dysregulation in the
      aging mouse brain.
AB  - Aging is associated with cerebrovascular dysregulation, which may underlie the
      increased susceptibility to ischemic stroke and vascular cognitive impairment
      occurring in the elder individuals. Although it has long been known that
      oxidative stress is responsible for the cerebrovascular dysfunction, the
      enzymatic system(s) generating the reactive oxygen species (ROS) have not been
      identified. In this study, we investigated whether the superoxide-producing
      enzyme NADPH oxidase is involved in alterations of neurovascular regulation
      induced by aging. Cerebral blood flow (CBF) was recorded by laser-Doppler
      flowmetry in anesthetized C57BL/6 mice equipped with a cranial window (age=3, 12,
      and 24 months). In 12-month-old mice, the CBF increases evoked by whisker
      stimulation or by the endothelium-dependent vasodilators acetylcholine and
      bradykinin were attenuated by 42, 36, and 53%, respectively (P<0.05). In
      contrast, responses to the nitric oxide donor S-nitroso-D-penicillamine or
      adenosine were not attenuated (P>0.05). These cerebrovascular effects were
      associated with increased production of ROS in neurons and cerebral blood
      vessels, assessed by hydroethidine microfluorography. The cerebrovascular
      impairment present in 12-month-old mice was reversed by the ROS scavenger Mn
      (III) tetrakis (4-benzoic acid) porphyrin chloride or by the NADPH oxidase
      peptide inhibitor gp91ds-tat, and was not observed in mice lacking the Nox2
      subunit of NADPH oxidase. These findings establish Nox2 as a critical source of
      the neurovascular oxidative stress mediating the deleterious cerebrovascular
      effects associated with increasing age.

PMID- 17429348
TI  - Evaluation of the stability of blood flow over time in the dominant hemisphere: a
      functional transcranial Doppler study.
AB  - Functional transcranial Doppler (fTCD) has been used for the identification of
      cerebral hemispheric dominance in various cognitive tasks. In our study, we have
      used fTCD with the aim to compare blood flow patterns in the hemispheres not only
      during the task activation periods but also in the post-stimulus phase. Normal
      volunteers, 25 right and 25 left-handed, were included. Mean flow velocities
      (FVs) in the bilateral middle cerebral arteries were recorded during the
      performance of six cognitive tasks and during the intervals between tasks. The
      lateralization index (LI) was calculated separately for each test (LI1-6), on the
      basis of the percent change of blood FV from baseline. To estimate flow
      fluctuations, a novel index, the LI-variability, was also calculated using a
      formula constituted by the minimum and maximum mean values recorded at specific
      time intervals during the entire procedure. Laterization indices, LI-3 and LI-4,
      corresponding to word generation and reading aloud tasks, produced the highest
      degree of activation. A perfect agreement (Cohen's kappa=1.000, P<0.001) was
      observed among LI-3, LI-4, and LI-V. The repetition of recordings gave excellent
      test-retest reliability in 10 randomly selected participants. Our results suggest
      that the hemisphere that is characterized as dominant by fTCD maintains a more
      stable flow pattern during the performance of successive cognitive tasks.
      Although it could not be considered as a clinically useful tool as yet, this
      observation introduces a novel parameter such as the stability of blood flow over
      time, which could potentially provide insight in the study of cerebral functions.

PMID- 17429349
TI  - Clinical pharmacology education and training at the National Institutes of
      Health.
AB  - In 1965, the National Institute of General Medical Sciences (NIGMS) established
      the intramural Pharmacology Research Associate Training (PRAT) program with the
      primary goals of providing postdoctoral training in pharmacology for individuals
      with or without previous pharmacology graduate training, and allowing individuals
      with doctoral degrees in pharmacology to obtain advanced training in other areas
      of science at the National Institutes of Health (NIH). The program utilized
      research preceptors drawn from laboratories that were conducting pharmacology
      related research at the NIH campus. Although primary emphasis was placed on
      training laboratory scientists, a number of PRAT fellows obtained training that
      enabled them to pursue successful careers in clinical pharmacology. A partial
      listing of these individuals is shown in Table 1. Eventually, a clinical
      pharmacology training option was formalized within the PRAT program by the
      appointment of a Clinical Pharmacology Program Director, but this was
      subsequently suspended when this individual left NIH for a position in the
      pharmaceutical industry.

PMID- 17429350
TI  - Vaporization as a smokeless cannabis delivery system: a pilot study.
AB  - Although cannabis may have potential therapeutic value, inhalation of a
      combustion product is an undesirable delivery system. The aim of the study was to
      investigate vaporization using the Volcano((R)) device as an alternative means of
      delivery of inhaled Cannabis sativa. Eighteen healthy inpatient subjects enrolled
      to compare the delivery of cannabinoids by vaporization to marijuana smoked in a
      standard cigarette. One strength (1.7, 3.4, or 6.8% tetrahydrocannabinol (THC))
      and delivery system was randomly assigned for each of the 6 study days. Plasma
      concentrations of Delta-9-THC, expired carbon monoxide (CO), physiologic and
      neuropsychologic effects were the main outcome measures. Peak plasma
      concentrations and 6-h area under the plasma concentration-time curve of THC were
      similar. CO levels were reduced with vaporization. No adverse events occurred.
      Vaporization of cannabis is a safe and effective mode of delivery of THC. Further
      trials of clinical effectiveness of cannabis could utilize vaporization as a
      smokeless delivery system.

PMID- 17429351
TI  - Change in erythropoietin pharmacokinetics following hematopoietic
      transplantation.
AB  - Pre-clinical studies have demonstrated that bone marrow ablation has a profound
      effect in decreasing erythropoietin (EPO) elimination. The study's objective was
      to determine in humans if EPO pharmacokinetics (PKs) are perturbed following bone
      marrow ablation. EPO PK studies were performed in eight subjects, aged 4 to 61
      years, undergoing fully myeloablative hematopoietic stem cell transplantation.
      Serial PK studies using intravenous injection of recombinant human EPO (92+/-2.0
      U/kg) (mean+/-SEM) were carried out during four periods of altered marrow
      integrity: baseline pre-ablation, post-ablation pre-transplant, early post
      transplant pre-engraftment, and late post-transplant full engraftment. Compared
      with baseline, post-ablation pre-transplant and early post-transplant EPO PKs
      demonstrated declines in clearance increases in terminal elimination half-life of
      36 and 95%, respectively. Clearance and half-life returned to baseline following
      full engraftment. The association of EPO elimination with decreased bone marrow
      activity in patients undergoing transplantation conclusively establishes the bone
      marrow as a key determinant of EPO elimination in humans.

PMID- 17429352
TI  - The carboxy terminus of NBS1 is required for induction of apoptosis by the MRE11
      complex.
AB  - The MRE11 complex (MRE11, RAD50 and NBS1) and the ataxia-telangiectasia mutated
      (ATM) kinase function in the same DNA damage response pathway to effect cell
      cycle checkpoint activation and apoptosis. The functional interaction between the
      MRE11 complex and ATM has been proposed to require a conserved C-terminal domain
      of NBS1 for recruitment of ATM to sites of DNA damage. Human Nijmegen breakage
      syndrome (NBS) cells and those derived from multiple mouse models of NBS express
      a hypomorphic NBS1 allele that exhibits impaired ATM activity despite having an
      intact C-terminal domain. This indicates that the NBS1 C terminus is not
      sufficient for ATM function. We derived Nbs1(DeltaC/DeltaC) mice in which the C
      terminal ATM interaction domain is deleted. Nbs1(DeltaC/DeltaC) cells exhibit
      intra-S-phase checkpoint defects, but are otherwise indistinguishable from wild
      type cells with respect to other checkpoint functions, ionizing radiation
      sensitivity and chromosome stability. However, multiple tissues of
      Nbs1(DeltaC/DeltaC) mice showed a severe apoptotic defect, comparable to that of
      ATM- or CHK2-deficient animals. Analysis of p53 transcriptional targets and ATM
      substrates showed that, in contrast to the phenotype of Chk2(-/-) mice,
      NBS1(DeltaC) does not impair the induction of proapoptotic genes. Instead, the
      defects observed in Nbs1(DeltaC/DeltaC) result from impaired phosphorylation of
      ATM targets including SMC1 and the proapoptotic factor, BID.

PMID- 17429353
TI  - A pre-existing hydrophobic collapse in the unfolded state of an ultrafast folding
      protein.
AB  - Insights into the conformational passage of a polypeptide chain across its free
      energy landscape have come from the judicious combination of experimental studies
      and computer simulations. Even though some unfolded and partially folded proteins
      are now known to possess biological function or to be involved in aggregation
      phenomena associated with disease states, experimentally derived atomic-level
      information on these structures remains sparse as a result of conformational
      heterogeneity and dynamics. Here we present a technique that can provide such
      information. Using a 'Trp-cage' miniprotein known as TC5b (ref. 5), we report
      photochemically induced dynamic nuclear polarization NMR pulse-labelling
      experiments that involve rapid in situ protein refolding. These experiments allow
      dipolar cross-relaxation with hyperpolarized aromatic side chain nuclei in the
      unfolded state to be identified and quantified in the resulting folded-state
      spectrum. We find that there is residual structure due to hydrophobic collapse in
      the unfolded state of this small protein, with strong inter-residue contacts
      between side chains that are relatively distant from one another in the native
      state. Prior structuring, even with the formation of non-native rather than
      native contacts, may be a feature associated with fast folding events in
      proteins.

PMID- 17429354
TI  - RNA-templated DNA repair.
AB  - RNA can act as a template for DNA synthesis in the reverse transcription of
      retroviruses and retrotransposons and in the elongation of telomeres. Despite its
      abundance in the nucleus, there has been no evidence for a direct role of RNA as
      a template in the repair of any chromosomal DNA lesions, including DNA double
      strand breaks (DSBs), which are repaired in most organisms by homologous
      recombination or by non-homologous end joining. An indirect role for RNA in DNA
      repair, following reverse transcription and formation of a complementary DNA, has
      been observed in the non-homologous joining of DSB ends. In the yeast
      Saccharomyces cerevisiae, in which homologous recombination is efficient, RNA was
      shown to mediate recombination, but only indirectly through a cDNA intermediate
      generated by the reverse transcriptase function of Ty retrotransposons in Ty
      particles in the cytoplasm. Although pairing between duplex DNA and single-strand
      (ss)RNA can occur in vitro and in vivo, direct homologous exchange of genetic
      information between RNA and DNA molecules has not been observed. We show here
      that RNA can serve as a template for DNA synthesis during repair of a chromosomal
      DSB in yeast. The repair was accomplished with RNA oligonucleotides complementary
      to the broken ends. This and the observation that even yeast replicative DNA
      polymerases such as alpha and delta can copy short RNA template tracts in vitro
      demonstrate that RNA can transfer genetic information in vivo through direct
      homologous interaction with chromosomal DNA.

PMID- 17429359
TI  - Climate change, here and now.

PMID- 17429358
TI  - Science without borders.

PMID- 17429360
TI  - When employees attack.

PMID- 17429362
TI  - Climate takes aim.

PMID- 17429363
TI  - Dinosaur prints lead to crediting row.

PMID- 17429364
TI  - Physicists question model of the Universe.

PMID- 17429365
TI  - Venezuelan free-speech row goes nuclear.

PMID- 17429368
TI  - Back to school.

PMID- 17429369
TI  - Plastic promises.

PMID- 17429370
TI  - Climate Change 2007: how to survive a warming world.

PMID- 17429371
TI  - Climate Change 2007: a world melting from the top down.

PMID- 17429372
TI  - Climate Change 2007: Al's army.

PMID- 17429373
TI  - Increasing prose quality by decreasing word repetition.

PMID- 17429374
TI  - Reliance on bibliometric databases can let you down.

PMID- 17429375
TI  - Save your notes, drafts and printouts: today's work is tomorrow's history.

PMID- 17429376
TI  - Climate change 2007: spring-time for sinks.

PMID- 17429381
TI  - Capturing human behaviour.

PMID- 17429382
TI  - Cancer: division of labour.

PMID- 17429383
TI  - Solid-state chemistry: crystal tennis rackets.

PMID- 17429385
TI  - Geology: crystal-clear ideas.

PMID- 17429386
TI  - Genomics: global views of leukaemia.

PMID- 17429387
TI  - Biophysics: quantum path to photosynthesis.

PMID- 17429388
TI  - Cell biology: fraternal twins.

PMID- 17429389
TI  - Ecology: Poole resources.

PMID- 17429390
TI  - Obituary: Knut Schmidt-Nielsen (1915-2007).

PMID- 17429391
TI  - Cell biology: autophagy and cancer.

PMID- 17429392
TI  - Multiple molecular mechanisms for multidrug resistance transporters.
AB  - The acquisition of multidrug resistance is a serious impediment to improved
      healthcare. Multidrug resistance is most frequently due to active transporters
      that pump a broad spectrum of chemically distinct, cytotoxic molecules out of
      cells, including antibiotics, antimalarials, herbicides and cancer
      chemotherapeutics in humans. The paradigm multidrug transporter, mammalian P
      glycoprotein, was identified 30 years ago. Nonetheless, success in overcoming or
      circumventing multidrug resistance in a clinical setting has been modest. Recent
      structural and biochemical data for several multidrug transporters now provide
      mechanistic insights into how they work. Organisms have evolved several elegant
      solutions to ridding the cell of such cytotoxic compounds. Answers are emerging
      to questions such as how multispecificity for different drugs is achieved, why
      multidrug resistance arises so readily, and what chance there is of devising a
      clinical solution.

PMID- 17429393
TI  - Mediators of vascular remodelling co-opted for sequential steps in lung
      metastasis.
AB  - Metastasis entails numerous biological functions that collectively enable
      cancerous cells from a primary site to disseminate and overtake distant organs.
      Using genetic and pharmacological approaches, we show that the epidermal growth
      factor receptor ligand epiregulin, the cyclooxygenase COX2, and the matrix
      metalloproteinases 1 and 2, when expressed in human breast cancer cells,
      collectively facilitate the assembly of new tumour blood vessels, the release of
      tumour cells into the circulation, and the breaching of lung capillaries by
      circulating tumour cells to seed pulmonary metastasis. These findings reveal how
      aggressive primary tumorigenic functions can be mechanistically coupled to
      greater lung metastatic potential, and how such biological activities may be
      therapeutically targeted with specific drug combinations.

PMID- 17429394
TI  - A laboratory demonstration of the capability to image an Earth-like extrasolar
      planet.
AB  - The detection and characterization of an Earth-like planet orbiting a nearby star
      requires a telescope with an extraordinarily large contrast at small angular
      separations. At visible wavelengths, an Earth-like planet would be 1 x 10(-10)
      times fainter than the star at angular separations of typically 0.1 arcsecond or
      less. There are several proposed space telescope systems that could, in
      principle, achieve this. Here we report a laboratory experiment that reaches
      these limits. We have suppressed the diffracted and scattered light near a star
      like source to a level of 6 x 10(-10) times the peak intensity in individual
      coronagraph images. In a series of such images, together with simple image
      processing, we have effectively reduced this to a residual noise level of about
      0.1 x 10(-10). This demonstrates that a coronagraphic telescope in space could
      detect and spectroscopically characterize nearby exoplanetary systems, with the
      sensitivity to image an 'Earth-twin' orbiting a nearby star.

PMID- 17429395
TI  - Optical coherent state discrimination using a closed-loop quantum measurement.
AB  - Quantum mechanics hinders our ability to determine the state of a physical system
      in two ways: individual measurements provide only partial information about the
      observed system (because of Heisenberg uncertainty), and measurements are
      themselves invasive-meaning that little or no refinement is achieved by further
      observation of an already measured system. Theoretical methods have been
      developed to maximize the information gained from a quantum measurement while
      also minimizing disturbance, but laboratory implementation of optimal measurement
      procedures is often difficult. The standard class of operations considered in
      quantum information theory tends to rely on superposition-basis and entangled
      measurements, which require high-fidelity implementation to be effective in the
      laboratory. Here we demonstrate that real-time quantum feedback can be used in
      place of a delicate quantum superposition, often called a 'Schrodinger cat
      state', to implement an optimal quantum measurement for discriminating between
      optical coherent states. Our procedure actively manipulates the target system
      during the measurement process, and uses quantum feedback to modify the
      statistics of an otherwise sub-optimal operator to emulate the optimal cat-state
      measurement. We verify a long-standing theoretical prediction and demonstrate
      feedback-mediated quantum measurement at its fundamental quantum limit over a non
      trivial region of parameter space.

PMID- 17429396
TI  - Rapid and reversible shape changes of molecular crystals on photoirradiation.
AB  - The development of actuators based on materials that reversibly change shape
      and/or size in response to external stimuli has attracted interest for some time.
      A particularly intriguing possibility is offered by light-responsive materials,
      which allow remote operation without the need for direct contact to the actuator.
      The photo-response of these materials is based on the photoisomerization of
      constituent molecules (typically trans-cis isomerization of azobenzene
      chromophores), which gives rise to molecular motions and thereby deforms the bulk
      material. This effect has been used to create light-deformable polymer films and
      gels, but the response of these systems is relatively slow. Here we report that
      molecular crystals based on diarylethene chromophores and with sizes ranging from
      10 to 100 micrometres exhibit rapid and reversible macroscopic changes in shape
      and size induced by ultraviolet and visible light. We find that on exposure to
      ultraviolet light, a single crystal of 1,2-bis(2-ethyl-5-phenyl-3
      thienyl)perfluorocyclopentene changes from a square shape to a lozenge shape,
      whereas a rectangular single crystal of 1,2-bis(5-methyl-2-phenyl-4
      thiazolyl)perfluorocyclopentene contracts by about 5-7 per cent. The deformed
      crystals are thermally stable, and switch back to their original state on
      irradiation with visible light. We find that our crystals respond in about 25
      microseconds (that is, about five orders of magnitude faster than the response
      time of the azobenzene-based polymer systems) and that they can move microscopic
      objects, making them promising materials for possible light-driven actuator
      applications.

PMID- 17429397
TI  - Evidence for wavelike energy transfer through quantum coherence in photosynthetic
      systems.
AB  - Photosynthetic complexes are exquisitely tuned to capture solar light
      efficiently, and then transmit the excitation energy to reaction centres, where
      long term energy storage is initiated. The energy transfer mechanism is often
      described by semiclassical models that invoke 'hopping' of excited-state
      populations along discrete energy levels. Two-dimensional Fourier transform
      electronic spectroscopy has mapped these energy levels and their coupling in the
      Fenna-Matthews-Olson (FMO) bacteriochlorophyll complex, which is found in green
      sulphur bacteria and acts as an energy 'wire' connecting a large peripheral light
      harvesting antenna, the chlorosome, to the reaction centre. The spectroscopic
      data clearly document the dependence of the dominant energy transport pathways on
      the spatial properties of the excited-state wavefunctions of the whole
      bacteriochlorophyll complex. But the intricate dynamics of quantum coherence,
      which has no classical analogue, was largely neglected in the analyses-even
      though electronic energy transfer involving oscillatory populations of donors and
      acceptors was first discussed more than 70 years ago, and electronic quantum
      beats arising from quantum coherence in photosynthetic complexes have been
      predicted and indirectly observed. Here we extend previous two-dimensional
      electronic spectroscopy investigations of the FMO bacteriochlorophyll complex,
      and obtain direct evidence for remarkably long-lived electronic quantum coherence
      playing an important part in energy transfer processes within this system. The
      quantum coherence manifests itself in characteristic, directly observable quantum
      beating signals among the excitons within the Chlorobium tepidum FMO complex at
      77 K. This wavelike characteristic of the energy transfer within the
      photosynthetic complex can explain its extreme efficiency, in that it allows the
      complexes to sample vast areas of phase space to find the most efficient path.

PMID- 17429398
TI  - A periodic shear-heating mechanism for intermediate-depth earthquakes in the
      mantle.
AB  - Intermediate-depth earthquakes, at depths of 50-300 km in subduction zones, occur
      below the brittle-ductile transition, where high pressures render frictional
      failure unlikely. Their location approximately coincides with 600 to 800 degrees
      C isotherms in thermal models, suggesting a thermally activated mechanism for
      their origin. Some earthquakes may occur by frictional failure owing to high pore
      pressure that might result from metamorphic dehydration. Because some
      intermediate-depth earthquakes occur approximately 30 to 50 km below the palaeo
      sea floor, however, the hydrous minerals required for the dehydration mechanism
      may not be present. Here we present an alternative mechanism to explain such
      earthquakes, involving the onset of highly localized viscous creep in pre
      existing, fine-grained shear zones. Our numerical model uses olivine flow laws
      for a fine-grained, viscous shear zone in a coarse-grained, elastic half space,
      with initial temperatures from 600-800 degrees C and background strain rates of
      10(-12) to 10(-15) s(-1). When shear heating becomes important, strain rate and
      temperature increase rapidly to over 1 s(-1) and 1,400 degrees C. The stress then
      drops dramatically, followed by low strain rates and cooling. Continued far-field
      deformation produces a quasi-periodic series of such instabilities.

PMID- 17429399
TI  - Egalitarian motives in humans.
AB  - Participants in laboratory games are often willing to alter others' incomes at a
      cost to themselves, and this behaviour has the effect of promoting cooperation.
      What motivates this action is unclear: punishment and reward aimed at promoting
      cooperation cannot be distinguished from attempts to produce equality. To
      understand costly taking and costly giving, we create an experimental game that
      isolates egalitarian motives. The results show that subjects reduce and augment
      others' incomes, at a personal cost, even when there is no cooperative behaviour
      to be reinforced. Furthermore, the size and frequency of income alterations are
      strongly influenced by inequality. Emotions towards top earners become
      increasingly negative as inequality increases, and those who express these
      emotions spend more to reduce above-average earners' incomes and to increase
      below-average earners' incomes. The results suggest that egalitarian motives
      affect income-altering behaviours, and may therefore be an important factor
      underlying the evolution of strong reciprocity and, hence, cooperation in humans.

PMID- 17429400
TI  - Conserved factors regulate signalling in Arabidopsis thaliana shoot and root stem
      cell organizers.
AB  - Throughout the lifespan of a plant, which in some cases can last more than one
      thousand years, the stem cell niches in the root and shoot apical meristems
      provide cells for the formation of complete root and shoot systems, respectively.
      Both niches are superficially different and it has remained unclear whether
      common regulatory mechanisms exist. Here we address whether root and shoot
      meristems use related factors for stem cell maintenance. In the root niche the
      quiescent centre cells, surrounded by the stem cells, express the homeobox gene
      WOX5 (WUSCHEL-RELATED HOMEOBOX 5), a homologue of the WUSCHEL (WUS) gene that non
      cell-autonomously maintains stem cells in the shoot meristem. Loss of WOX5
      function in the root meristem stem cell niche causes terminal differentiation in
      distal stem cells and, redundantly with other regulators, also provokes
      differentiation of the proximal meristem. Conversely, gain of WOX5 function
      blocks differentiation of distal stem cell descendents that normally
      differentiate. Importantly, both WOX5 and WUS maintain stem cells in either a
      root or shoot context. Together, our data indicate that stem cell maintenance
      signalling in both meristems employs related regulators.

PMID- 17429401
TI  - Synthetic lethal screen identification of chemosensitizer loci in cancer cells.
AB  - Abundant evidence suggests that a unifying principle governing the molecular
      pathology of cancer is the co-dependent aberrant regulation of core machinery
      driving proliferation and suppressing apoptosis. Anomalous proteins engaged in
      support of this tumorigenic regulatory environment most probably represent
      optimal intervention targets in a heterogeneous population of cancer cells. The
      advent of RNA-mediated interference (RNAi)-based functional genomics provides the
      opportunity to derive unbiased comprehensive collections of validated gene
      targets supporting critical biological systems outside the framework of
      preconceived notions of mechanistic relationships. We have combined a high
      throughput cell-based one-well/one-gene screening platform with a genome-wide
      synthetic library of chemically synthesized small interfering RNAs for systematic
      interrogation of the molecular underpinnings of cancer cell chemoresponsiveness.
      NCI-H1155, a human non-small-cell lung cancer line, was employed in a paclitaxel
      dependent synthetic lethal screen designed to identify gene targets that
      specifically reduce cell viability in the presence of otherwise sublethal
      concentrations of paclitaxel. Using a stringent objective statistical algorithm
      to reduce false discovery rates below 5%, we isolated a panel of 87 genes that
      represent major focal points of the autonomous response of cancer cells to the
      abrogation of microtubule dynamics. Here we show that several of these targets
      sensitize lung cancer cells to paclitaxel concentrations 1,000-fold lower than
      otherwise required for a significant response, and we identify mechanistic
      relationships between cancer-associated aberrant gene expression programmes and
      the basic cellular machinery required for robust mitotic progression.

PMID- 17429404
TI  - Effects of the dopamine D3 receptor (DRD3) gene polymorphisms on risperidone
      response: a pharmacogenetic study.
AB  - Previous observations of the anatomical distribution and pharmacological profile
      of the dopamine D(3) receptor (DRD3) have indicated its potential role in
      antipsychotic drug action. Risperidone, an effective first-line atypical
      antipsychotic agent, exhibits a relatively high affinity for this receptor.
      Recent studies have reported an association of the Ser9Gly polymorphism in the
      DRD3 gene with therapeutic response to risperidone, but the results were
      inconsistent. We therefore postulated that the Ser9Gly polymorphism might be in
      linkage disequilibrium with an undetected variant that exerts a direct influence
      on risperidone efficacy. The present study genotyped eight single nucleotide
      polymorphisms (SNPs) distributed throughout the DRD3 gene and examined five of
      these for association with treatment outcome, following an 8-week period of
      risperidone monotherapy in 130 schizophrenic patients from mainland China.
      Clinical symptoms were assessed before and after the treatment period, using the
      Brief Psychiatry Rating Scale (BPRS). The confounding effects of non-genetic
      factors were estimated and the baseline symptom score was included as a covariate
      for adjustment. Neither was any association observed between the five
      polymorphisms and improvement in total BPRS scores nor was any combined effect of
      these variants detected in the haplotype analysis. The current results indicate
      that genetic variations within the DRD3 gene may not contribute significantly to
      interindividual differences in the therapeutic efficacy of risperidone.

PMID- 17429405
TI  - A non-additive interaction of a functional MAO-A VNTR and testosterone predicts
      antisocial behavior.
AB  - A functional VNTR polymorphism in the promoter of the monoamine oxidase A gene
      (MAOA-LPR) has previously been shown to be an important predictor of antisocial
      behavior in men. Testosterone analogues are known to interact with the MAOA
      promoter in vitro to influence gene transcription as well as in vivo to influence
      CSF levels of the MAO metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in human
      males. We examined the possible joint effects of testosterone (measured in CSF)
      and MAOA-LPR genotype on antisocial personality disorder and scores on the Brown
      Goodwin Aggression scale in 95 unrelated male criminal alcoholics and 45
      controls. The results confirm that MAOA genotype and CSF testosterone interact to
      predict antisocial behaviors. The MAOA/testosterone interaction also predicted
      low levels of CSF MHPG, which tentatively suggests the possibility that the
      interaction may be mediated by a direct effect on gene transcription. If
      replicated these findings offer plausible explanations for previous
      inconsistencies in studies of the relationship between testosterone and male
      human aggression, as well as for how MAOA genotype may influence aggressive
      behavior in human males.

PMID- 17429406
TI  - Differential regulation of the mesoaccumbens dopamine circuit by serotonin2C
      receptors in the ventral tegmental area and the nucleus accumbens: an in vivo
      microdialysis study with cocaine.
AB  - Stimulation of central serotonin2C receptor (5-HT(2C)R) inhibits dopamine (DA)
      dependent neurochemical and behavioral effects of cocaine, while 5-HT(2C)Rs
      locally expressed into the ventral tegmental area (VTA) and the nucleus accumbens
      (NAc) exert opposite functional control over cocaine-induced behavioral effects.
      Using in vivo microdialysis in halothane-anesthetized rats, we tested the
      hypothesis that this functionally opposite regulation of the mesoaccumbens DA
      pathway relies on the ability of 5-HT(2C)Rs in the VTA and the NAc to inhibit and
      enhance respectively cocaine-induced accumbal DA outflow. Intra-VTA injection of
      the 5-HT(2C)R agonist Ro 60-0175 at 5 microg/0.2 microl, but not 1 microg/0.2
      microl, attenuated the increase in accumbal DA outflow induced by the systemic
      administration of 10 mg/kg of cocaine. Intra-VTA injection of the 5-HT(2C)R
      antagonist SB 242084 at either dose (0.1 or 0.5 microg/0.2 microl) did not modify
      the effects of cocaine. Intra-NAc application of Ro 60-0175 dose-dependently
      excited (0.1 microM) and inhibited (1 microM) cocaine-induced DA outflow. In
      contrast, intra-NAc application of SB 242084 resulted in diametrically opposite
      effects when applied at these concentrations. These results further support the
      idea that the overall action of central 5-HT(2C)Rs on accumbal DA output is
      dependent, at least in part, on the functional balance between different 5
      HT(2C)R populations within the NAc and within the mesoaccumbens DA pathway (VTA
      vs NAc).

PMID- 17429407
TI  - Deep brain stimulation to reward circuitry alleviates anhedonia in refractory
      major depression.
AB  - Deep brain stimulation (DBS) to different sites allows interfering with
      dysfunctional network function implicated in major depression. Because a
      prominent clinical feature of depression is anhedonia--the inability to
      experience pleasure from previously pleasurable activities--and because there is
      clear evidence of dysfunctions of the reward system in depression, DBS to the
      nucleus accumbens might offer a new possibility to target depressive
      symptomatology in otherwise treatment-resistant depression. Three patients
      suffering from extremely resistant forms of depression, who did not respond to
      pharmacotherapy, psychotherapy, and electroconvulsive therapy, were implanted
      with bilateral DBS electrodes in the nucleus accumbens. Stimulation parameters
      were modified in a double-blind manner, and clinical ratings were assessed at
      each modification. Additionally, brain metabolism was assessed 1 week before and
      1 week after stimulation onset. Clinical ratings improved in all three patients
      when the stimulator was on, and worsened in all three patients when the
      stimulator was turned off. Effects were observable immediately, and no side
      effects occurred in any of the patients. Using FDG-PET, significant changes in
      brain metabolism as a function of the stimulation in fronto-striatal networks
      were observed. No unwanted effects of DBS other than those directly related to
      the surgical procedure (eg pain at sites of implantation) were observed.
      Dysfunctions of the reward system--in which the nucleus accumbens is a key
      structure--are implicated in the neurobiology of major depression and might be
      responsible for impaired reward processing, as evidenced by the symptom of
      anhedonia. These preliminary findings suggest that DBS to the nucleus accumbens
      might be a hypothesis-guided approach for refractory major depression.

PMID- 17429408
TI  - Estimation of D2-like receptor occupancy by dopamine in the putamen of
      hemiparkinsonian Monkeys.
AB  - To advance understanding of the neurochemical changes in Parkinson's disease
      (PD), we compared D2-like dopamine receptor occupancy by dopamine in the control
      and lesioned putamen of four pig-tailed macaques treated unilaterally with MPTP.
      PET and in vitro binding techniques were used to measure binding potential
      (BP(*)) and density of D2-like dopamine receptors (B(max)), respectively. As
      would be expected in PD, relatively higher values of BP(*) and B(max) and less
      amphetamine-induced decrease in [(11)C]raclopride binding were observed in the
      lesioned compared with the contralateral putamen in each animal. The percent
      differences between lesioned and contralateral sides were similar whether the
      measurements were of [(11)C]raclopride BP(*) or B(max) values, measured in vivo
      and in vitro, respectively. As [(11)C]raclopride BP(*) is a measure of the
      density of D2-like dopamine receptors available for radioligand binding (i.e.,
      not occupied by dopamine), these findings suggest that the fractional occupancy
      of receptors by endogenous dopamine in the lesioned putamen is nearly equal to
      that in the contralateral putamen. Therefore, the absolute number of receptors
      occupied by dopamine, which is a product of receptor density and fractional
      occupancy by dopamine, is greater in the lesioned than in the contralateral
      putamen. One possible explanation for the lack of differences in fractional
      occupancy of D2 receptors by dopamine (despite a loss in available dopamine) is a
      lesion-induced increase in a portion of low-affinity D2 receptors to a state of
      high affinity for dopamine.

PMID- 17429409
TI  - Arousal and stress effects on consolidation and reconsolidation of recognition
      memory.
AB  - This study examined the effects of the arousal level of the rat and exposure to a
      behavioral stressor on consolidation and reconsolidation of a nonaversive
      learning paradigm, the object recognition task. Learning was tested under two
      arousal conditions: no previous habituation to the experimental context (high
      novelty stress/arousal level) or extensive prior habituation (reduced novelty
      stress/arousal level). Results indicated that in the habituated rats, exposure to
      an out-of-context stressor (ie, elevated platform stress) impaired long-term
      consolidation and reconsolidation of object recognition. RU-486, a glucocorticoid
      receptor (GR) antagonist, infused into the basolateral amygdala (BLA), reversed
      the impairing effects of the stressor. In contrast, the nonhabituated aroused
      rats were impaired when consolidation was examined, but their memory was intact
      following reactivation of the memory trace. Exposure of nonhabituated rats to an
      out-of-context stressor enhanced the long-term consolidation of recognition
      memory, but impaired reconsolidation, and the effects were reversed by a GR
      antagonist infused into the BLA. Additionally, nonhabituated control rats showed
      intact retrieval following microinfusion of propranolol to the BLA immediately
      after the training, suggesting an involvement of beta-adrenoceptors in the BLA in
      the arousal-induced impairment of consolidation. These findings demonstrate
      opposite effects, detrimental and facilitative, of arousal and stress on memory
      consolidation and reconsolidation. In addition, the data suggests that although
      some general features underlie consolidation and reconsolidation, there is a
      possible dissimilarity between the two processes, which is dependent on the
      arousal level of the animal during training.

PMID- 17429410
TI  - Behavioral effects of chronic fluoxetine in BALB/cJ mice do not require adult
      hippocampal neurogenesis or the serotonin 1A receptor.
AB  - We previously reported that chronic, but not subchronic, treatment with the
      selective serotonin reuptake inhibitor (SSRI) fluoxetine altered behavior in the
      forced swimming test (FST) in BALB/cJ mice. We now use this model to investigate
      mechanisms underlying the delayed onset of the behavioral response to
      antidepressants, specifically (1) adult hippocampal neurogenesis and (2)
      expression of the 5-HT1A receptor. Here, we show data validating this model of
      chronic antidepressant action. We found the FST to be selectively responsive to
      chronic administration of the SSRI fluoxetine (18 mg/kg/day) and the tricyclic
      antidepressant desipramine (20 mg/kg/day), but not to the antipsychotic
      haloperidol (1 mg/kg/day) in BALB/cJ mice. The behavioral effects of fluoxetine
      emerged by 12 days of treatment, and were affected neither by ablation of
      progenitor cells of the hippocampus nor by genetic deletion of the 5-HT1A
      receptor. The effect of fluoxetine in the BALB/cJ mice was also neurogenesis
      independent in the novelty-induced hypophagia test. We also found that chronic
      fluoxetine does not induce an increase in cell proliferation or the number of
      young neurons as measured by BrdU and doublecortin immunolabeling, respectively,
      in BALB/cJ mice. These data are in contrast to our previous report using a
      different strain of mice (129SvEvTac). In conclusion, we find that BALB/cJ mice
      show a robust response to chronic SSRI treatment in the FST, which is not
      mediated by an increase in new neurons in the hippocampus, and does not require
      the 5-HT1A receptor. These findings suggest that SSRIs can produce antidepressant
      like effects via distinct mechanisms in different mouse strains.

PMID- 17429411
TI  - Exposure to stressors during juvenility disrupts development-related alterations
      in the PSA-NCAM to NCAM expression ratio: potential relevance for mood and
      anxiety disorders.
AB  - Childhood trauma is associated with higher rates of both mood and anxiety
      disorders in adulthood. The exposure of rats to stressors during juvenility has
      comparable effects, and was suggested as a model of induced predisposition for
      these disorders. The neural cell adhesion molecule (NCAM) and its polysialylated
      form PSA-NCAM are critically involved in neural development, activity-dependent
      synaptic plasticity, and learning processes. We examined the effects of exposure
      to stressors during juvenility on coping with stressors in adulthood and on NCAM
      and PSA-NCAM expression within the rat limbic system both soon after the exposure
      and in adulthood. Exposure to stressors during juvenility reduced novel-setting
      exploration and impaired two-way shuttle avoidance learning in adulthood. Among
      naive rats, a development-related decrease of about 50% was evident in the PSA
      NCAM to NCAM expression ratio in the basolateral amygdala, in the CA1 and dentate
      gyrus regions of the hippocampus, and in the entorhinal cortex. In juvenile
      stressed rats, we found no such decrease, but rather an increase in the
      polysialylation of NCAM ( approximately 50%), evident soon after the exposure to
      juvenile stress and also in adulthood. Our results suggest that exposure to
      stressors during juvenility alters the maturation of the limbic system, and
      potentially underlies the predisposition to exhibit stress-related symptoms in
      adulthood.

PMID- 17429412
TI  - Increased anterior cingulate/medial prefrontal cortical glutamate and creatine in
      bipolar depression.
AB  - Proton magnetic resonance spectroscopy ((1)HMRS) is an in vivo brain imaging
      method that can be used to investigate psychotropic drug mechanism of action.
      This study evaluated baseline (1)HMRS spectra of bipolar depressed patients and
      whether the level of cerebral metabolites changed after an open trial of
      lamotrigine, an anti-glutamatergic mood stabilizer. Twenty-three bipolar
      depressed and 12 control subjects underwent a MRS scan of the anterior
      cingulate/medial prefrontal cortex. The scan was performed on a GE whole-body 1.5
      T MRI scanner using single-voxel PRESS (TE/TR=30/3000 ms, 3 x 3 x 3 cm(3) and
      post-processed offline with LCModel. Baseline CSF-corrected absolute
      concentrations of glutamate+glutamine ([Glx]), glutamate ([Glu]), and
      creatine+phosphocreatine ([Cr]) were significantly higher in bipolar depressed
      subjects vs healthy controls. The non-melancholic subtype had significantly
      higher baseline [Glx] and [Glu] levels than the melancholic subtype. Remission
      with lamotrigine was associated with significantly lower post-treatment glutamine
      ([Gln]) in comparison to non-remission. These data suggest that non-melancholic
      bipolar depression is characterized by increased glutamate coupled with increased
      energy expenditure. Lamotrigine appears to reduce glutamine levels associated
      with treatment remission. Further study is encouraged to determine if these MR
      spectroscopic markers can delineate drug mechanism of action and subsequent
      treatment response.

PMID- 17429413
TI  - Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell
      response in patients with pulmonary tuberculosis.
AB  - Challenged by scattered understanding of protective immunity to Mycobacterium
      tuberculosis (MTB), we have mapped peptide epitopes to human leukocyte antigen
      (HLA)-A*0101, A*0201, A*1101, A*2402, B*0702, B*0801 and B*1501 of the secreted
      mycobacterial antigen Ag85B, a vaccine candidate that may be associated with
      immune protection. Affinity (ED(50)) and half-life (t(1/2), off-rate) analysis
      for individual peptide species on HLA-A and HLA-B molecules revealed binding
      ranges between 10(-3) and 10(-7) M. After selection of the best matches, major
      histocompatibility complex class I/peptide tetramer complexes were constructed to
      measure the CD8+ T-cell responses directly ex vivo in peripheral blood
      mononuclear cells (PBMC) derived from 57 patients with acute pulmonary
      tuberculosis. Three patterns of (allele-) specific CD8+ recognition were
      identified: (a). Focus on one dominant epitope with additional recognition of
      several subdominant T-cell epitopes (HLA-A*0301, A*2402, B*0801 and B*1501); (b).
      Co-dominant recognition of two distinct groups of peptides presented by HLA
      B*0702; and (c). Diverse and broad recognition of peptides presented by HLA
      A*0201. Peptides that bound with slow off-rates to class I alleles, that is HLA
      A*0201, were associated with low frequency of CD8+ T cells in PBMCs from patients
      with tuberculosis. HLA-B alleles showed fast off-rates in peptide binding and
      restricted high numbers (up to 6%) of antigen-specific CD8+ T cells in patients
      with pulmonary tuberculosis.

PMID- 17429416
TI  - Yin and Yang: The Dao of the kidney.

PMID- 17429414
TI  - Study of proinflammatory responses induced by Yersinia pestis in human monocytes
      using cDNA arrays.
AB  - Yersinia pestis, the causative agent of plague, is known to develop strategies to
      overcome the host immune mechanisms and survive in the host. The molecular
      changes induced by Y. pestis in the host are not well delineated. Here, we
      examined the early events triggered after the intracellular infection of Y.
      pestis in human monocytes and lymphocytes by analyzing the host transcriptional
      profiles using cDNA arrays. We found that sets of genes that, especially at early
      time periods, were highly upregulated in monocytes alone when compared with a
      mixed culture of lymphocytes and monocytes. Gene expression responses revealed
      genes coding for cytokines, chemokines, transcription factors, inflammatory and
      apoptosis-related genes. Protein levels were measured, and real-time polymerase
      chain reaction was used to validate the microarray results. Our data suggest that
      intracellular infection of human monocytes with Y. pestis results in a strong
      inflammatory response at early time periods and a downregulation of genes such as
      thromobomodulin, which may play a role in coagulation, resulting in disseminated
      intravascular coagulation, a primary cause of death in plague infected hosts. We
      provide evidence that genomic analysis can provide a solid foundation to
      mechanistic insights to explain some of the symptoms induced by Y. pestis.

PMID- 17429417
TI  - How to control lymphangiogenesis: a novel role for rapamycin.
AB  - Analysis of the lymphatic microvasculature has become possible only recently by
      the discovery of novel proteins specifically expressed in lymphatic endothelial
      cells only. Therapeutic manipulation of de novo lymphangiogenesis might become
      clinically relevant in the future in diverse situations, such as renal transplant
      rejection. In this issue Huber et al. demonstrate that rapamycin acts as an
      efficient inhibitor of lymphangiogenesis.

PMID- 17429418
TI  - Metabolic risk factors and renal disease.
AB  - Accumulating evidence supports that components of the metabolic syndrome coexist
      with both albuminuria and chronic kidney disease (CKD). The article by
      Tomaszewski et al. indicates that this interrelation exists in young obese men
      before overt renal or cardiovascular disease and also suggests that early
      treatment of hypertension is especially compelling to prevent the evolution of
      renal hyperfiltration to CKD.

PMID- 17429419
TI  - Urinary tract infections revisited.
AB  - Urinary tract infections (UTIs) remain a significant clinical problem, despite
      antibiotic treatment and surgical correction of reflux and malformations. Here we
      propose that novel molecular tools may be applied to modernize and individualize
      the diagnosis and therapy of UTI. Determinants of bacterial virulence and host
      resistance are relatively well understood at the molecular level, and technology
      for their detection is within reach.

PMID- 17429422
TI  - Survival differences between activated injectable vitamin D2 and D3 analogs.

PMID- 17429424
TI  - Iodixanol vs ioxaglate for preventing contrast nephropathy: who is winner?

PMID- 17429425
TI  - Osseous and myeloid metaplasia in a failed renal allograft.

PMID- 17429426
TI  - Acquired perforating dermatosis in a peritoneal dialysis patient.

PMID- 17429427
TI  - ABC transporters and drug resistance in leukemia: was P-gp nothing but the first
      head of the Hydra?
AB  - More than 30 years ago it was discovered that permeability glycoprotein (P-gp)
      can cause drug resistance. Over the following decades numerous studies showed
      that high expression of P-gp is associated with poor prognosis in acute myeloid
      leukemia in adults and that it causes multidrug resistance via ATP-dependent drug
      efflux. It was hoped that an inhibition of P-gp could sensitize resistant
      leukemic cells to chemotherapy and thus improve treatment results. Today we know
      that the family of ATP-binding cassette transporters (ABC transporters) comprises
      48 different proteins. Some of them seem to be able to cause drug resistance as
      well as P-gp. This review focuses on emerging data on the clinical relevance of
      other ABC transporters, such as BCRP, MRP3, and ABCA3. When Heracles fought the
      ancient Hydra, he had to fight all the heads at ones but only one head was vital
      for the beast. Can we block all the relevant ABC transporters at once? Is there
      one transporter that is more important than the others?

PMID- 17429428
TI  - Junctional adhesion molecule C (JAM-C) distinguishes CD27+ germinal center B
      lymphocytes from non-germinal center cells and constitutes a new diagnostic tool
      for B-cell malignancies.
AB  - Differentiation of naive B cells into plasma cells or memory cells occurs in the
      germinal centers (GCs) of lymph follicles or alternatively via a GC- and T-cell
      independent pathway. It is currently assumed that B-cell lymphomas correlate to
      normal B-cell differentiation stages, but the precise correlation of several B
      cell lymphomas to these two pathways remains controversial. In the present
      report, we describe the junctional adhesion molecule C (JAM-C), currently
      identified at the cell-cell border of endothelial cells, as a new B-cell marker
      with a tightly regulated expression during B-cell differentiation. Expression of
      JAM-C in tonsils allows distinction between two CD27+ B-cell subpopulations: JAM
      C- GC B cells and JAM-C+ non-germinal B cells. The expression of JAM-C in
      different B-cell lymphomas reveals a disease-specific pattern and allows a clear
      distinction between JAM-C- lymphoproliferative syndromes (chronic lymphocytic
      leukemia, mantle cell lymphoma and follicular lymphoma) and JAM-C+ ones (hairy
      cell leukemia, marginal zone B-cell lymphoma). Therefore, we propose JAM-C as a
      new identification tool in B-cell lymphoma diagnosis.

PMID- 17429429
TI  - Gene expression profiling of precursor T-cell lymphoblastic leukemia/lymphoma
      identifies oncogenic pathways that are potential therapeutic targets.
AB  - We compared the gene expression pattern of thymic tumors from precursor T-cell
      lymphoblastic lymphoma/leukemia (pre-T LBL) that arose in transgenic mice that
      overexpressed SCL, LMO1 or NUP98-HOXD13 (NHD13) with that of thymocytes from
      normal littermates. Only two genes, Ccl8 and Mrpl38, were consistently more than
      fourfold overexpressed in pre-T LBL from all three genotypes analyzed, and a
      single gene, Prss16 was consistently underexpressed. However, we identified a
      number of genes, such as Cfl1, Tcra, Tcrb, Pbx3, Eif4a, Eif4b and Cox8b that were
      over or under-expressed in pre-T LBL that arose in specific transgenic lines.
      Similar to the situation seen with human pre-T LBL, the SCL/LMO1 leukemias
      displayed an expression profile consistent with mature, late cortical thymocytes,
      whereas the NHD13 leukemias displayed an expression profile more consistent with
      immature thymocytes. We evaluated two of the most differentially regulated genes
      as potential therapeutic targets. Cfl1 was specifically overexpressed in SCL-LMO1
      tumors; inactivation of Cfl1 using okadaic acid resulted in suppression of
      leukemic cell growth. Overexpression of Ccl8 was a consistent finding in all
      three transgenic lines, and an antagonist for the Ccl8 receptor-induced death of
      leukemic cell lines, suggesting a novel therapeutic approach.

PMID- 17429432
TI  - Resistance reversal by RNAi silencing of MDR1 in CML cells associated with
      increase in imatinib intracellular levels.

PMID- 17429433
TI  - The origin of eukaryotes: a reappraisal.
AB  - Ever since the elucidation of the main structural and functional features of
      eukaryotic cells and subsequent discovery of the endosymbiotic origin of
      mitochondria and plastids, two opposing hypotheses have been proposed to account
      for the origin of eukaryotic cells. One hypothesis postulates that the main
      features of these cells, including their ability to capture food by endocytosis
      and to digest it intracellularly, were developed first, and later had a key role
      in the adoption of endosymbionts; the other proposes that the transformation was
      triggered by an interaction between two typical prokaryotic cells, one of which
      became the host and the other the endosymbiont. Re-examination of this question
      in the light of cell-biological and phylogenetic data leads to the conclusion
      that the first model is more likely to be the correct one.

PMID- 17429434
TI  - A mouse mutation in the 12R-lipoxygenase, Alox12b, disrupts formation of the
      epidermal permeability barrier.
AB  - Nonbullous congenital ichthyosiform erythroderma (NCIE) is a nonsyndromic form of
      autosomal recessive congenital ichthyosis characterized by hyperkeratosis and a
      disruption in the epidermal permeability barrier. Identification of mutations in
      two lipoxygenases (LOXs), ALOX12B (12R-LOX) and ALOXE3 (eLOX3), and further
      functional studies implicate ALOX12B and ALOXE3 in the etiology of NCIE. Here, we
      report a mutation in Alox12b in the recessive ethylnitrosurea-induced mouse
      mutant, mummy (Alox12b(mmy-Bei)). mummy mutants have red, scaly skin and die
      perinatally. Histologically, mummy mutants display defects in the epidermis. We
      mapped mummy to a 1.9 Mb interval on Chr. 11 containing Alox12b (12R-LOX), Aloxe3
      (eLOX3) and Alox15b (8-LOX). Sequencing of all three genes identified a nonsense
      mutation in the catalytic domain of Alox12b. We demonstrate that mummy mutants
      have a disrupted epidermal permeability barrier and that the nonsense mutation in
      mummy abolishes the enzyme activity of 12R-LOX. The mummy mutant provides a mouse
      model for LOX-mediated NCIE and is the first described mouse mutant affecting
      epidermal barrier formation identified by forward genetics.

PMID- 17429435
TI  - Serotonin activates human monocytes and prevents apoptosis.
AB  - Monocytes play a critical role in chronic atopic dermatitis (AD) and are the
      primary leukocytes that interact with activated platelets. Although activated
      platelets release a variety of mediators, the role of platelets in cutaneous
      allergic inflammation remains unclear. Serotonin (5-hydroxytryptamine, 5-HT) is
      one of the prototypic mediators produced by activated platelets. We examined the
      effect of 5-HT on the function and lifespan of human monocytes. Normal human
      monocytes treated with 5-HT exhibited upregulated expression of costimulatory
      molecules, enhanced capacity to produce cytokines following lipopolysaccharide
      treatment, and to stimulate allogeneic CD4+ T cells. 5-HT also attenuated the
      apoptosis in normal human monocytes in a dose-dependent manner. The plasma levels
      of 5-HT were increased in patients with AD compared with controls and correlated
      with the SCORAD index. 5-HT also inhibited monocyte apoptosis in these patients.
      5-HT upregulated Bcl-2 and Mcl-1, and inhibited the activation of caspase-3. The
      effects of 5-HT on monocyte apoptosis were mediated by the 5-HT1 and/or 5-HT7
      receptors. 5-HT and a 5-HT(1/6/7)-receptor agonist induced phosphorylation of
      extracellular signal-regulated kinase1/2 and activation of nuclear transcription
      factor-kappaB. These findings support that 5-HT activates monocytes and inhibits
      apoptosis, allowing them to remain in the tissue and contribute to chronic
      inflammation.

PMID- 17429436
TI  - Hair follicle regeneration using grafted rodent and human cells.
AB  - Hair follicle regeneration involves epithelial-mesenchymal interactions (EMIs) of
      follicular epithelial and dermal papilla (DP) cells. Co-grafting of those
      cellular components from mice allows complete hair reconstitution. However,
      regeneration of human hair in a similar manner has not been reported. Here, we
      investigated the possibility of cell-based hair generation from human cells. We
      found that DP-enriched cells (DPE) are more critical than epidermal cells in
      murine hair reconstitution on a cell number basis, and that murine DPE are also
      competent for hair regeneration with rat epidermal cells. Co-grafting of human
      keratinocytes derived from neonatal foreskins with murine DPE produced hair
      follicle-like structures consisting of multiple epidermal cell layers with a well
      keratinized innermost region. Those structures expressed hair follicle-specific
      markers including hair keratin, and markers expressed during developmental
      stages. However, the lack of regular hair structures indicates abnormal
      folliculogenesis. Similar hair follicle-like structures were also generated with
      cultured human keratinocytes after the first passage, or with keratinocytes
      derived from adult foreskins, demonstrating that epidermal cells even at a mature
      stage can differentiate in response to inductive signals from DP cells. This
      study emphasizes the importance of EMI in follicular generation and the
      differentiation potential of epidermal keratinocytes.

PMID- 17429437
TI  - Mitogen- and stress-activated protein kinase 2 and cyclic AMP response element
      binding protein are activated in lesional psoriatic epidermis.
AB  - The activity of the p38 mitogen-activated protein kinases (MAPKs) is increased in
      lesional psoriatic skin, supporting a possible role of these kinases in the
      pathogenesis of psoriasis. Recently, increased focal activation of the downstream
      target mitogen- and stress-activated protein kinase 1 (MSK1) was demonstrated in
      psoriatic epidermis. The purpose of this study is to investigate MSK2 and the
      transcription factor cyclic adenosine monophosphate response element-binding
      protein (CREB) in psoriatic skin and in cultured normal human keratinocytes. In
      lesional psoriatic skin, significantly increased MSK2 (Ser196) and CREB (Ser133)
      activation was demonstrated by phospho blotting. Immunofluorescence staining of
      phosphorylated MSK2 (Ser196) revealed colocalization with phosphorylated MSK1
      (Thr 581) in the epidermis. Keratinocyte cultures stimulated with anisomycin and
      IL-1beta showed increased MSK2 (Ser196) and CREB (Ser133) phosphorylation. Such
      activation was abolished during preincubation with a p38 inhibitor. Keratinocytes
      transfected with small interfering RNA showed a stronger decrease in CREB
      phosphorylation in MSK1/2 double-transfected cells than in MSK1 and MSK2 single
      transfected cells. This study demonstrate for the first time the expression of
      MSK2 in keratinocytes and increased MSK2 and CREB activation in lesional
      psoriatic skin. Our results indicate that the p38-MAPK/MSK1/MSK2 and CREB
      signalling pathway may play a role in the pathogenesis of psoriasis.

PMID- 17429438
TI  - HaCaT keratinocytes overexpressing the S100 proteins S100A8 and S100A9 show
      increased NADPH oxidase and NF-kappaB activities.
AB  - The calcium- and arachidonic acid (AA)-binding proteins S100A8 and S100A9 are
      involved in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      activation in phagocytes. They are specifically expressed in myeloid cells, and
      are also found in epithelial cells in various (patho)physiological conditions. We
      have investigated the consequences of S100A8/A9 overexpression in epithelial cell
      lines on reactive oxygen species (ROS) generation and downstream signaling.
      Epithelial carcinoma HeLa cells, which exclusively express Nox2, showed
      dramatically increased activation of NADPH oxidase by phorbol 12-myristate 13
      acetate after S100A8/A9 gene transfection. HaCaT keratinocytes overexpressing
      S100A8/A9 showed enhanced, transient ROS generation in response to the calcium
      ionophore A23187 compared to mock-transfected cells. Polymerase chain reaction
      analysis revealed mRNA transcripts for Nox1, Nox2, and Nox5 in HaCaT
      keratinocytes. Detailed transfection studies confirmed that NADPH oxidase
      activities in Nox1- and Nox5-transfected HeLa cells were enhanced after S100A8/A9
      gene complementation. Furthermore, mutational analysis revealed that AA binding
      and Thr113 phosphorylation are important for S100A8/A9-enhanced activation of
      NADPH oxidase. Nuclear factor-kappaB (NF-kappaB) activation and interleukin-8
      mRNA levels were increased in S100A8/A9-HaCaT keratinocytes, consistent with the
      view that NF-kappaB is a redox-sensitive transcription factor. Because they are
      expressed in epithelia under specific conditions, S100A8 and S100A9 might be
      involved in skin pathogenesis by modulating aspects of downstream signaling.

PMID- 17429439
TI  - Activation of the IL-1beta-processing inflammasome is involved in contact
      hypersensitivity.
AB  - The inflammasome is a cytosolic protein complex regulating the activation of
      caspase-1, which cleaves the pro-inflammatory cytokines IL-1beta and IL-18 into
      their active form. The inflammasome is composed of a NACHT-, LRR- and pyrin
      (NALP) family member that acts as a sensor for danger signals and the adaptor
      protein apoptosis-associated speck-like protein containing a CARD domain (ASC),
      which allows the recruitment of caspase-1 in the complex. In the skin, exposure
      to contact sensitizers (CS) such as trinitro-chlorobenzene causes an immune
      response called contact hypersensitivity (CHS) or eczema. In this delayed-type
      hypersensitivity response, efficient priming of the adaptive immunity depends on
      the concomitant activation of the innate immune system, including IL-1beta/IL-18
      activation in the skin. To determine if the inflammasome contributes to CHS, we
      have analyzed its capacity to react to CS in vitro and in vivo. We show here that
      key components of the inflammasome are present in human keratinocytes and that CS
      like trinitro-chlorobenzene induce caspase-1/ASC dependent IL-1beta and IL-18
      processing and secretion. We also show that ASC- and NALP3-deficient mice display
      an impaired response to CS. These findings suggest that CS act as danger signals
      that activate the inflammasome in the skin, and reveal a new role of NALP3 and
      ASC as regulators of innate immunity in CHS.

PMID- 17429440
TI  - A novel mutation in K6b in pachyonychia congenita type 2.

PMID- 17429441
TI  - Absence of cutaneous TNFalpha-producing CD4+ T cells and TNFalpha may allow for
      fibrosis rather than epithelial cytotoxicity in murine sclerodermatous graft
      versus-host disease, a model for human scleroderma.
AB  - Graft-versus-host disease (GVHD) is a complication of hematopoietic cell
      transplantation and is a major source of morbidity and mortality. Two main forms
      of GVHD occur: cytotoxic GVHD (Cyt GVHD), in which TNFalpha is a critical
      cytokine in epithelial injury, and sclerodermatous GVHD (Scl GVHD), in which
      TGFbeta plays a major role in fibrosis. To understand the critical early events
      in GVHD and scleroderma, we are studying a murine model that uses differences in
      minor histocompatibility antigens to generate Scl GVHD. We asked the question:
      what is the immune environment in this model that promotes fibrosis rather than
      the epithelial injury of Cyt GVHD? We found that in Scl GVHD, cutaneous CD4+ T
      cells produced IFNgamma and IL-2 but not TNFalpha, also absent by gene array
      analysis. The role of cutaneous CD4+ T cells in Scl GVHD may not be an active
      process through production of TGFbeta, but may rather be a passive one due to
      lack of antigen-presenting cell (APC) support for CD4+ T cells and failure to
      produce TNFalpha, a potent inhibitor of TGFbeta-induced fibrosis as well as
      inducer of keratinocyte apoptosis. These APC-T cell interactions and the cytokine
      environment promote fibrosis rather than cytotoxic epithelial injury in skin in
      Scl GVHD.

PMID- 17429442
TI  - Thromboxane A2 induces itch-associated responses through TP receptors in the skin
      in mice.
AB  - Thromboxane A2 (TXA2), a metabolite of arachidonic acid produced by
      cyclooxygenase and thromboxane synthase, is thought to participate in chronic
      dermatitis. This study investigated the involvement of TXA2 in cutaneous itch. An
      intradermal injection of U-46619, a stable analogue of TXA2, elicited scratching,
      an itch-associated response, in mice. Dose-response curve was bell shaped with a
      maximum effect at 10 nmol per site. The action of U-46619 was inhibited by a
      coinjection of the TP antagonist ONO-3708 and was abolished by TP receptor
      deficiency. TP receptor was mainly expressed in nerve fiber in the skin and
      keratinocytes. Thromboxane synthase was also expressed in keratinocytes. U-46619
      increased intracellular Ca2+ ion concentration in primary cultures of dorsal root
      ganglion neurons and keratinocytes. The results suggest that TXA2 synthesized by
      keratinocytes acts as an itch mediator. It may elicit itch through the activation
      of TP receptors on primary afferents and keratinocytes; keratinocytes may produce
      itch mediators including TXA2. Thus, thromboxane synthase inhibitor and TP
      receptor antagonists will be candidates for antipruritic medicines.

PMID- 17429443
TI  - Smad3 signal transducer regulates skin inflammation and specific IgE response in
      murine model of atopic dermatitis.
AB  - Atopic dermatitis (AD) is a common chronic inflammatory skin disease
      characterized by itchy, dry, and inflamed skin. Transforming growth factor (TGF)
      beta is an important fibrogenic and immunomodulatory factor that regulates
      cellular processes in the injured and inflamed skin. This study examines the role
      of the TGF-beta-Smad signaling pathway using Smad3-deficient mice in a murine
      model of AD. Dermatitis was induced in mice by epicutaneous application of
      ovalbumin (OVA) applied in a patch to tape-stripped skin. OVA-specific IgE and
      IgG2a antibody levels were measured by ELISA. Skin biopsies from sensitized skin
      areas were used for RNA isolation, histology, and immunohistochemical
      examination. The thickness of dermis was significantly reduced in OVA-sensitized
      skin of Smad3-/- mice. The defect in the dermal thickness was accompanied by a
      decrease in the expression of mRNA for proinflammatory cytokines IL-6 and IL
      1beta in the OVA-sensitized skin. In contrast, the number of mast cells was
      significantly increased in OVA-sensitized skin of Smad3-/- mice, which also
      exhibited elevated levels of OVA-specific IgE. These results demonstrate that the
      Smad3-pathway regulates allergen-induced skin inflammation and systemic IgE
      antibody production in a murine model AD. The Smad3 signaling pathway might be a
      potential target in the therapy of allergic skin diseases.

PMID- 17429444
TI  - Mouse models of psoriasis.
AB  - Psoriasis is a T-cell-mediated chronic inflammatory skin disease believed to be
      of autoimmune nature that can be triggered or worsened by streptococcal throat
      infections. In addition to conventional chronic inflammatory changes, psoriasis
      is characterized by complex and striking alterations in epidermal growth and
      differentiation. Psoriasis is generally not observed in animals other than man,
      and this lack of a suitable animal model has greatly hindered research into the
      pathogenesis of psoriasis. Multiple transgenic, knockout, and reconstituted
      models of psoriasis have been developed over the past two decades. Despite their
      limitations, these models have demonstrated that keratinocyte hyperplasia,
      vascular hyperplasia, and cell-mediated immunity in the skin are closely
      interrelated. Xenograft models, in which involved and uninvolved psoriatic skin
      are transplanted onto immunodeficient mice, are the only models that come close
      to incorporating the complete genetic, immunologic, and phenotypic changes of the
      disease. They have shown conclusively that psoriasis is a T-cell-mediated
      disease, and have been used to elucidate novel pathogenic pathways. In this
      review, we describe various animal models, detail the immunologic and
      intracellular pathways that mediate these phenotypes and assess the utility of
      these models to better understand this disease.

PMID- 17429445
TI  - Enhanced antiglioma activity of chimeric HCMV/HSV-1 oncolytic viruses.
AB  - Oncolytic herpes simplex virus (HSV)-1 gamma(1)34.5-deletion mutants
      (Deltagamma(1)34.5 HSV) are promising agents for tumor therapy. The attenuating
      mutation renders the virus aneurovirulent but also limits late viral protein
      synthesis and efficient replication in many tumors. We tested whether one
      function of gamma(1)34.5 gene, which mediates late viral protein synthesis
      through host protein kinase R (PKR) antiviral response evasion, could be
      restored, without restoring the neurovirulence. We have previously reported the
      construction of two chimeric Deltagamma(1)34.5 HSV vectors (chimeric HSV), C130
      and C134, which express the human cytomegalovirus (HCMV) PKR-evasion genes TRS1
      and IRS1, respectively. We now demonstrate the following. The HCMV/HSV-1 chimeric
      viruses (i) maintain late viral protein synthesis in the human malignant glioma
      cells tested (D54-MG, U87-MG and U251-MG); (ii) replicate to higher titers than
      Deltagamma(1)34.5 HSV in malignant glioma cells in vitro and in vivo; (iii) are
      aneurovirulent; and (iv) are superior to other Deltagamma(1)34.5 HSV with both
      improved reduction of tumor volumes in vivo, and improved survival in two
      experimental murine brain tumor models. These findings demonstrate that transfer
      of HCMV IRS1 or TRS1 gene into Deltagamma(1)34.5 HSV significantly improves
      replication in malignant gliomas without restoring wild-type neurovirulence,
      resulting in enhanced tumor reduction and prolonged survival.

PMID- 17429446
TI  - Ambulatory blood pressure, target organ damage and aortic root size in never
      treated essential hypertensive patients.
AB  - The relationship between ambulatory blood pressure (ABP), target organ damage
      (TOD) and aortic root (AR) size in human hypertension has not been fully explored
      to date. We investigated the relationship between ABP, different markers of TOD
      and AR size in never-treated essential hypertensive patients. A total of 519
      grade 1 and 2 hypertensive patients (mean age 46+/-12 years) referred for the
      first time to our outpatient clinic underwent the following procedures: (1)
      routine examination, (2) 24 h urine collection for microalbuminuria (MA), (3)
      ambulatory blood pressure monitoring over two 24 h periods within 4 weeks, (4)
      echocardiography and (5) carotid ultrasonography. AR dilatation was defined by
      sex-specific criteria (> or =40 mm in men and > or =37 mm in women). AR diameter
      was increased in 3.7% of patients. Demographic variables (body mass index, age
      and male gender), average night-time diastolic blood pressure (BP) (but not
      clinic or average 48 h BP), left ventricular mass index and carotid intima-media
      (IM) thickness showed an independent association with AR size in both univariate
      and multivariate analyses. When TOD data were analysed in a categorical way, a
      stepwise increase in the prevalence of left ventricular hypertrophy (LVH)
      (I=17.5%, II=27.6%, III=35.8%) and carotid IM thickening (I=20.9%, II=28.8%,
      III=34.4%), but not in MA (I=6.8%, II=9.1%, III=8.7%) was found with the
      progression of AR size tertiles. Our results show that (1) AR enlargement in
      uncomplicated never-treated hypertensive patients has a markedly lower prevalence
      than traditional markers of cardiac and extracardiac TOD; (2) night-time BP, LVH
      and carotid IM thickening are independent predictors of AR dimension.

PMID- 17429447
TI  - Circulating endothelial cells in preeclampsia.
AB  - Endothelial dysfunction plays an important role in the pathogenesis of
      preeclampsia. Increased number of circulating endothelial cells (CECs) have
      previously been reported after various diseases associated endothelial injury.
      The aim of this study was to evaluate the CECs in patients with preeclampsia and
      to demonstrate any association between CECs and homocysteine, which is another
      marker of vascular injury. The study included 20 preeclamptic, 15 hypertensive
      women, 15 healthy pregnant and 15 healthy non-pregnant women. All subjects had
      normal renal function. Systolic and diastolic blood pressures, serum homocysteine
      levels were measured. To isolate CECs, peripheral blood was first incubated with
      anti-CD-146 antibody and subsequently conjugated to immunomagnetic beads. Cells
      were stained with acridine and counted. Preeclamptic patients had elevated
      numbers of CECs (13.2+/-5.2 cells/ml) compared with hypertensive patients (6.9+/
      0.8 cells/ml), healthy pregnants (5.2+/-1.4 cells/ml), and non-pregnant controls
      (4.0+/-1.8 cells/ml), (P<0.0001). Serum homocysteine level in preeclamptic
      patients (9.5+/-2.8 micromol/l) was significantly higher compared with healthy
      pregnants (6.0+/-0.6 micromol/l), was not different from hypertensive patients
      (11.5+/-2.3 micromol/l, P>0.05), but it was lesser compared with non-pregnant
      controls (12.2+/-3.3 micromol/l, P<0.0001). Also, significant correlation between
      CECs and systolic blood pressure (P<0.0001, r=0.63), diastolic blood pressure
      (P<0.0001, r=0.64) and serum homocysteine (P<0.01, r=0.55) levels were found in
      preeclamptic patients. CECs as a marker of endothelial injury were significantly
      higher in patients with preeclampsia than in hypertensive patients, healthy
      pregnants and normal controls. Further studies are needed for the prognostic and
      potential importance of CECs in preeclampsia.

PMID- 17429448
TI  - Polymorphisms of angiotensinogen and angiotensin-converting enzyme associated
      with lower extremity arterial disease in the Health, Aging and Body Composition
      study.
AB  - The role of renin-angiotensin system (RAS) genes on the risk of lower extremity
      arterial disease (LEAD) in elderly people remains unclear. We assessed the
      relationship of genetic polymorphisms in RAS: G-6A, T174M and M235T of the
      angiotensinogen (AGT) gene, and the angiotensin-converting enzyme
      insertion/deletion (ACE_I/D) variant to the risk of LEAD in the Health, Aging and
      Body Composition (Health ABC) Study. This analysis included 1228 black and 1306
      white men and women whose age ranged between 70 and 79 years at the study
      enrollment. LEAD was defined as ankle-arm index (AAI) <0.9. Genotype-phenotype
      associations were estimated by regression analyses with and without adjustment
      for established cardiovascular disease (CVD) risk factors. The proportion of LEAD
      was significantly higher in black (21.1%) than that in white elderly people
      (10.1%, P<0.0001). The distribution of AGT polymorphisms was also significantly
      different between black and white participants. There was no statistically
      significant association between the selected RAS genetic variants and LEAD after
      adjustment for age, antihypertensive medications, lipid-lowering medication, pack
      year smoking, body mass index, low-density lipoprotein cholesterol, and prevalent
      diabetes and coronary heart disease. However, A-T haplotype of G-6A and M235T
      interacting with homozygous ACE_II (beta=-1.07, P=0.006) and with ACE inhibitors
      (beta=-1.03, P=0.01) significantly decreased the risk of LEAD in white but not in
      black participants after adjustment for the selected CVD risk factors. In
      conclusion, the study observed a gene-gene and gene-drug interaction for LEAD in
      the white elderly.

PMID- 17429449
TI  - Polarization analysis of surface-relief D-fiber Bragg gratings.
AB  - Surface-relief fiber Bragg gratings exhibit substantially more polarization
      dependence than standard fiber Bragg gratings. Using D-fiber with different core
      orientations, surface-relief gratings are analyzed and fabricated to determine
      the polarization dependence. We show that the largest Bragg reflection occurs for
      the polarization state with a dominant TE field component parallel to the flat
      surface of the fiber. The polarization dependence is adjusted by changing the
      index of refraction of the surrounding media and by fabricating the surface
      relief grating using rotated core D-fiber.

PMID- 17429450
TI  - Analysis of nonlinear frequency sweep in high-speed tunable laser sources using a
      self-homodyne measurement and Hilbert transformation.
AB  - We have proposed and demonstrated a novel measurement technique for
      characterizing nonlinear frequency sweep in high-speed tunable laser sources by
      using a simple self-homodyne setup and Hilbert transformation. Measurement
      results, such as the variation in frequency scanning rate during a frequency
      sweeping process, are presented for a temperature-tuned distributed feedback
      laser diode and external cavity tunable laser. The time-varying optical phase of
      the incident light of a laser is calculated from the integration of the
      instantaneous optical frequency, and the tuning rate is obtained from its
      derivative.

PMID- 17429451
TI  - Eliminating chromatic aberration in Gauss-type lens design using a novel genetic
      algorithm.
AB  - Two different types of Gauss lens design, which effectively eliminate primary
      chromatic aberration, are presented using an efficient genetic algorithm (GA).
      The current GA has to deal with too many targets in optical global optimization
      so that the performance is not much improved. Generally speaking, achromatic
      aberrations have a great relationship with variable glass sets for all elements.
      For optics whose design is roughly convergent, glass sets for optics will play a
      significant role in axial and lateral color aberration. Therefore better results
      might be derived from the optimal process of eliminating achromatic aberration,
      which could be carried out by finding feasible glass sets in advance. As an
      alternative, we propose a new optimization process by using a GA and involving
      theories of geometrical optics in order to select the best optical glass
      combination. Two Gauss-type lens designs are employed in this research. First, a
      telephoto lens design is sensitive to axial aberration because of its long focal
      length, and second, a wide-angle Gauss design is complicated by lateral color
      aberration at the extreme corners because Gauss design is well known not to deal
      well with wide-angle problems. Without numbers of higher chief rays passing the
      element, it is difficult to correct lateral color aberration altogether for the
      Gauss design. The results and conclusions show that the attempts to eliminate
      primary chromatic aberrations were successful.

PMID- 17429452
TI  - Generating light with a specified spectral power distribution.
AB  - A particular version of a spectral integrator has been designed. It consists of a
      xenon lamp whose light is dispersed into a color spectrum by dispersing prisms.
      Using a transmissive LCD panel controlled by a computer, certain fractions of the
      light in different parts of the spectrum are masked out. The remaining
      transmitted light is integrated and projected onto a translucent diffusing plate.
      A spectroradiometer that measures the generated light is also attached to the
      computer, thus making the spectral integrator a closed-loop system. An algorithm
      for generating the light of a specified spectral power distribution has been
      developed. The resulting measured spectra differ from the specified ones with
      relative rms errors in the range of 1%-20% depending on the shape of the spectral
      power distribution.

PMID- 17429453
TI  - Aberration production using a high-resolution liquid-crystal spatial light
      modulator.
AB  - Phase-only liquid-crystal spatial light modulators provide a powerful means of
      wavefront control. With high resolution and diffractive (modulo 2pi) operation,
      they can accurately represent large-dynamic-range phase maps. As a result, they
      provide an excellent means of producing electrically controllable, dynamic, and
      repeatable aberrations. However, proper calibration is critical to achieving
      accurate phase maps. Several calibration methods from previous literature were
      considered. With simplicity and accuracy in mind, we selected one method for each
      type of necessary calibration. We augmented one of the selected methods with a
      new step that improves its accuracy. After calibrating our spatial light
      modulator with our preferred methods, we evaluated its ability to produce
      aberrations in the laboratory. We studied Zernike polynomial aberrations using
      interferometry and Fourier-transform-plane images, and atmospheric aberrations
      using a Shack-Hartmann wavefront sensor. These measurements show the closest
      agreement with theoretical expectations that we have seen to date.

PMID- 17429454
TI  - Analysis of hexagonal array geometry for free-space optical interconnects with
      improved signal-to-noise ratio.
AB  - The effect of transmitter and receiver array configurations on the performance of
      free-space optical interconnects (FSOIs) was investigated. Experimentally
      measured, spectrally resolved, near-field images of vertical-cavity surface
      emitting laser (VCSEL) transverse modes were used as extended sources in our
      simulation model and combined with laser relative intensity noise and the
      receiver noise to determine the optimal array geometry. Our results demonstrate
      the importance of stray-light cross talk in both square and hexagonal
      configurations. By changing the array lattice geometry from square to hexagonal,
      we obtained an overall optical signal-to-noise ratio improvement of 3 dB. We
      demonstrated that the optical signal-to-noise ratio is optimal for the hexagonal
      channel arrangement regardless of the transverse mode structure of the VCSEL
      beam. We also determined the VCSEL drive current required for the best
      performance of the FSOI system.

PMID- 17429455
TI  - Nondestructive readout of a photorefractive hologram by phase-conjugate copying
      in a one-crystal configuration.
AB  - We propose a novel phase-conjugate copying method for nondestructive readout of a
      volatile photorefractive hologram. In the one-crystal configuration, two
      holographic memories and a mutually pumped phase conjugator (MPPC) are formed
      within a single photorefractive crystal, instead of using multiple crystals. Two
      memories share the same hologram and complement each other in refreshing the
      hologram. A MPPC suppresses fanning noise and automatically aligns the wavefront
      of the reference and readout beams. We found the optimum configuration to achieve
      nondestructive readout from calculations and geometric consideration. In the
      experiments with a BaTiO(3) crystal, a continuous readout of 20 times longer than
      the recording time was achieved.

PMID- 17429456
TI  - Humidity's influence on visible region refractive index structure parameter
      C(n)(2).
AB  - In the near-infrared and visible bandpasses optical propagation theory
      conventionally assumes that humidity does not contribute to the effects of
      atmospheric turbulence on optical beams. While this assumption may be reasonable
      for dry locations, we demonstrate that there is an unequivocal effect owing to
      the presence of humidity upon the strength of turbulence parameter, C(n)(2), from
      data collected in the Chesapeake Bay area over 100 m length horizontal
      propagation paths. We describe and apply a novel technique, Hilbert phase
      analysis, to the relative humidity, temperature, and C(n)(2) data to show the
      contribution of the relevant climate variable to C(n)(2) as a function of time.

PMID- 17429458
TI  - Extension of Chandrasekhar's formula to a nonhomogeneous Lambertian surface and
      comparison with the 6S formulation.
AB  - The classical Chandrasekhar's formula, which relates the surface albedo to the
      top of the atmosphere radiance, rigorously applies to a homogeneous Lambertian
      surface. For a nonhomogeneous Lambertian surface in a plane-parallel atmosphere,
      an extension of this formula was proposed in the 1980s and has been implemented
      recently in the 6S algorithm. To analyze this extension, the rigorous formula of
      the top of the atmosphere signal in a plane-parallel atmosphere bounded by a
      nonhomogeneous Lambertian surface is derived. Then the 6S algorithm extension is
      compared to the exact formula and approximations and their validity is examined.
      The derivation of the exact formula is based on the separation of the radiation
      fields into direct and diffuse components, on the introduction of the Green's
      function of the problem, and on integrations of boundary values of the radiation
      fields with Green's function.

PMID- 17429457
TI  - Parameterization of aerosol and cirrus cloud effects on reflected sunlight
      spectra measured from space: application of the equivalence theorem.
AB  - An original methodology to account for aerosol and cirrus cloud contributions to
      reflected sunlight is described. This method can be applied to the problem of
      retrieving greenhouse gases from satellite-observed data and is based on the
      equivalence theorem with further parameterization of the photon path-length
      probability density function (PPDF). Monte Carlo simulation was used to validate
      this parameterization for a vertically nonhomogeneous atmosphere including an
      aerosol layer and cirrus clouds. Initial approximation suggests that the PPDF
      depends on four parameters that can be interpreted as the effective cloud height,
      cloud relative reflectance, and two additional factors to account for photon path
      length distribution under the cloud. We demonstrate that these parameters can be
      efficiently retrieved from the nadir radiance measured in the oxygen A-band and
      from the H(2)O-saturated area of the CO(2) 2.0 microm spectral band.

PMID- 17429459
TI  - Pulsed laser deposited ZnO film on side-polished fiber as a gas sensing element.
AB  - A simple sensor element consisting of a side-polished single-mode fiber and a
      planar metal oxide waveguide is described. The thin ZnO planar waveguide was
      produced on the polished fiber surface by pulsed laser deposition at optimized
      processing parameters. A measurement scheme for in situ control of the film
      thickness during the deposition process was developed and used. X-ray diffraction
      measurements and scanning electron microscopy were used to characterize the
      structure and the surface morphology of the planar waveguide, respectively. The
      numerical evaluation of the sensor sensitivity predicts the possibility to detect
      refractive index changes of less than 10(-4). Furthermore, preliminary gas sensor
      tests were performed by using a mixture of 1.5% butane diluted in N(2) and pure
      butane. A shift of the spectral position of the resonance points was observed
      from 3 to 5 s after gas exposure, which corresponds to refractive index changes
      of 3 x 10(-5) and 1.2 x 10(-3) for 1.5% butane and for pure butane, respectively.

PMID- 17429460
TI  - Fiber-optic microphones for battlefield acoustics.
AB  - We describe recent work to evaluate the potential performance of an
      interferometric fiber-optic microphone for battlefield acoustics. The microphone
      design has high sensitivity and flat response at low frequency and is readily
      multiplexed. The design is simple and could be manufactured at low cost, which is
      desirable since in operation the sensors may need to be disposable. Field trial
      results from an array of microphones are discussed.

PMID- 17429461
TI  - Simplified transformation circle theory in analyzing a laser resonator.
AB  - Transformation circle theory is simpler than other methods for analyzing laser
      resonators. In our analysis only sigma circles and simple mathematical knowledge
      are used to analyze the stability and calculate the parameters of the laser
      resonator, which further simplifies the transformation theory. The results agree
      well with the well-known matrix theory. Two- and three-mirror (including a
      thermal lens) laser resonators are used as examples to present the stability
      formula and the Gaussian beam dimensions at the mirrors. Furthermore, we apply
      the commonly used example in which the laser medium is close to the cavity
      mirror.

PMID- 17429462
TI  - Development of a compact efficient 10 Hz 20 TW Ti:sapphire laser system with a 1
      kHz regenerative amplifier.
AB  - We have constructed a compact efficient Ti:sapphire laser system that generates
      30 fs, 630 mJ pulses at a repetition rate of 10 Hz. A new geometry for a single
      stage multipass power amplifier is proposed that greatly weakens and even makes
      use of thermal lensing. Such geometry can realize high output in a single-stage
      power amplifier; otherwise at least two-stage power amplifiers are required. The
      new configuration simplifies the laser system and reduces the cost. The key point
      in this design is that the beam spot size evolution is considered in combination
      with the pulse amplification.

PMID- 17429463
TI  - Broadband spectroscopic sensor for real-time monitoring of industrial SO(2)
      emissions.
AB  - A spectroscopic system for continuous real-time monitoring of SO(2)
      concentrations in industrial emissions was developed. The sensor is well suited
      for field applications due to simple and compact instrumental design, and robust
      data evaluation based on ultraviolet broadband absorption without the use of any
      calibration cell. The sensor has a detection limit of 1 ppm, and was employed
      both for gas-flow simulations with and without suspended particles, and for in
      situ measurement of SO(2) concentrations in the flue gas emitted from an
      industrial coal-fired boiler. The price/performance ratio of the instrument is
      expected to be superior to other comparable real-time monitoring systems.

PMID- 17429464
TI  - Laser-induced breakdown spectroscopy of bulk aqueous solutions at oceanic
      pressures: evaluation of key measurement parameters.
AB  - The development of in situ chemical sensors is critical for present-day
      expeditionary oceanography and the new mode of ocean observing systems that we
      are entering. New sensors take a significant amount of time to develop;
      therefore, validation of techniques in the laboratory for use in the ocean
      environment is necessary. Laser-induced breakdown spectroscopy (LIBS) is a
      promising in situ technique for oceanography. Laboratory investigations on the
      feasibility of using LIBS to detect analytes in bulk liquids at oceanic pressures
      were carried out. LIBS was successfully used to detect dissolved Na, Mn, Ca, K,
      and Li at pressures up to 2.76 x 10(7) Pa. The effects of pressure, laser-pulse
      energy, interpulse delay, gate delay, temperature, and NaCl concentration on the
      LIBS signal were examined. An optimal range of laser-pulse energies was found to
      exist for analyte detection in bulk aqueous solutions at both low and high
      pressures. No pressure effect was seen on the emission intensity for Ca and Na,
      and an increase in emission intensity with increased pressure was seen for Mn.
      Using the dual-pulse technique for several analytes, a very short interpulse
      delay resulted in the greatest emission intensity. The presence of NaCl enhanced
      the emission intensity for Ca, but had no effect on peak intensity of Mn or K.
      Overall, increased pressure, the addition of NaCl to a solution, and temperature
      did not inhibit detection of analytes in solution and sometimes even enhanced the
      ability to detect the analytes. The results suggest that LIBS is a viable
      chemical sensing method for in situ analyte detection in high-pressure
      environments such as the deep ocean.

PMID- 17429465
TI  - Low-cost high-sensitivity strain and temperature sensing using graded-index
      multimode fibers.
AB  - We report a low-loss, low-cost high-sensitivity all-fiber strain and temperature
      sensor based on mode interference in graded-index multimode fibers. Blueshifts
      with strain and temperature sensitivities of 18.6 pm/microstrain and 58.5 pm/
      degrees C have been observed. Experimental results show that smaller core
      diameter graded-index fibers display greater strain-induced peak wavelength
      shifts than larger core diameter fibers.

PMID- 17429466
TI  - Polarization-sensitive optical coherence tomography for imaging human
      atherosclerosis.
AB  - Polarization-sensitive optical coherence tomography (PS-OCT) combines the
      advantages of OCT with image contrast enhancement, which is based on its ability
      to detect phase retardation and the fast-axis angle. Both PS-OCT images and
      histopathology have demonstrated similar features that allowed differentiation of
      atherosclerotic structures (i.e., plaques) from normal tissue. Moreover, the
      picrosirius polarization method was used to confirm PS-OCT assessment of collagen
      in the fibrous cap of atherosclerotic plaques, and high-frequency (40 MHz)
      ultrasound images were used to identify calcium in the vessel wall. Our
      preliminary ex vivo investigation of human aortic specimens indicated that PS-OCT
      might help to identify atherosclerotic lesions.

PMID- 17429467
TI  - Light propagation in multilayered scattering media beyond the diffusive regime.
AB  - We describe a method to solve the radiative transfer equation (RTE) in
      multilayered geometry with index mismatch and demonstrate its potential for
      modeling light propagation in biological systems. The method is compared to Monte
      Carlo simulations with high accuracy but is much more efficient in terms of
      computer time. We illustrate the potential of the method by studying a
      multilayered system containing a weakly scattering layer surrounded by highly
      scattering layers, with anisotropic scattering and index mismatched interfaces.
      The calculation of directional transmitted fluxes has shown that the RTE method
      can be used to calculate relevant quantities in realistic systems in the presence
      of non-diffusive behavior.

PMID- 17429468
TI  - Validation of luminescent source reconstruction using single-view spectrally
      resolved bioluminescence images.
AB  - We characterize the capabilities and limitations of the Living Image Software 3D
      Analysis package (Xenogen, Alameda, California) in the reconstruction of
      calibrated light sources. Sources shallower than the mean free path of light
      propagation suffered reconstruction inaccuracy. For sources deeper than the mean
      free path, the average error in depth and intensity reconstruction was less than
      4% and 12%, respectively, for homogeneous tissue. The reconstruction of
      luminescent beads implanted within an optically heterogeneous mouse abdomen
      proved less accurate. The ability to distinguish multiple sources decreased with
      increasing source depth. A number of factors influence the accuracy of light
      source reconstruction.

PMID- 17429470
TI  - Image, eye, and retina (invited review).
AB  - Advances in understanding the initial stages of the visual process have been made
      over the centuries. This heritage will be reviewed with respect to the passage of
      light through the eye, as well as its gross anatomy and microscopic structure.
      The links between image formation in the camera and the eye were integrated with
      the anatomy of the eye in the seventeenth century. They drew attention to the
      problem of accommodation and to corrections for errors of refraction.
      Investigations of the structure of the retina were to await the invention of
      achromatic microscopes in the early nineteenth century. An armory of devices for
      examining vision and the eye were to follow later in the century. These
      transformed the study of vision from an observational to an experimental
      discipline.

PMID- 17429471
TI  - Maximum permissible exposures for ocular safety (ANSI 2000), with emphasis on
      ophthalmic devices.
AB  - After discussing the rationale and assumptions of the ANSI Z136.1-2000 Standard
      for protection of the human eye from laser exposure, we present the concise
      formulation of the exposure limits expressed as maximum permissible radiant
      exposure (in J/cm(2)) for light overfilling the pupil. We then translate the
      Standard to a form that is more practical for typical ophthalmic devices or in
      vision research situations, implementing the special qualifications of the
      Standard. The safety limits are then expressed as radiant power (watts) entering
      the pupil of the eye. Exposure by repetitive pulses is also addressed, as this is
      frequently employed in ophthalmic applications. Examples are given that will
      familiarize potential users with this format.

PMID- 17429472
TI  - Designing a holographic modal wavefront sensor for the detection of static ocular
      aberrations.
AB  - The extent to which holographic modal wavefront sensing can be applied to the
      detection of ocular aberrations was investigated. First, the idea of extending
      the dynamic range of the sensor by increasing the mask bias and the collection
      area of the pinhole detectors used in the sensor is reviewed. Errors in the
      detection of single-mode aberrations owing to reduced coherence from retinal
      scattering, photon, readout, and quantization noise are evaluated. A sensitivity
      to-noise metric is introduced to evaluate sensor designs and is found to be
      maximized by using a pinhole detector radius of 8.6(flambda/NDelta) for every
      wave of mask bias (where f=transform lens focal length, lambda=wavelength, and N
      and Delta are the number and size of the hologram pixels, respectively). The
      problem of detecting ocular aberrations composed of multiple modes required a
      generalization of the sensitivity measure to include all incident aberration
      modes. A "detect and correct" ocular aberration detection scheme was implemented
      that reduced the effects of cross talk and showed a maximum sensitivity-to-noise
      ratio of 40, which varied inversely with the size of the ocular aberration being
      detected.

PMID- 17429473
TI  - Photon signal detection and evaluation in the adaptive optics scanning laser
      ophthalmoscope.
AB  - To select a suitable photodetector for an adaptive optics scanning laser
      ophthalmoscope (AOSLO) and evaluate its performance, we characterized the signal
      and noise properties in the AOSLO photon detection and derived the signal-to
      noise ratio (SNR). Using the SNR as the main criterion, we chose the best
      detector from a selection of four photomultiplier tubes (PMTs) and three
      avalanche photodiodes (APDs). We conducted a comprehensive evaluation of the
      performance of the selected detector on our AOSLO. The study presents a practical
      strategy that can be used to test the photodetector for either initial evaluation
      or subsequent performance in in-line inspection.

PMID- 17429474
TI  - Characterizing image quality in a scanning laser ophthalmoscope with differing
      pinholes and induced scattered light.
AB  - We quantify the effects on scanning laser ophthalmoscope image quality of
      controlled amounts of scattered light, confocal pinhole diameter, and age.
      Optical volumes through the optic nerve head were recorded for a range of pinhole
      sizes in 12 subjects (19-64 years). The usefulness of various overall metrics in
      quantifying the changes in fundus image quality is assessed. For registered and
      averaged images, we calculated signal-to-noise ratio, entropy, and acutance.
      Entropy was best able to distinguish differing image quality. The optimum
      confocal pinhole diameter was found to be 50 microm (on the retina), providing
      improved axial resolution and image quality under all conditions.

PMID- 17429475
TI  - Effect of aberrations and scatter on image resolution assessed by adaptive optics
      retinal section imaging.
AB  - The effect of increased high-order wavefront aberrations on image resolution was
      investigated, and the performance of adaptive optics (AO) for correcting
      wavefront error in the presence of increased light scatter was assessed in a
      model eye. An AO section imaging system provided an oblique view of a model
      retina and incorporated a wavefront sensor and deformable mirror for measurement
      and compensation of wavefront aberrations. Image resolution was quantified by the
      width of a Lorentzian curve fitted to a laser line image. Wavefront aberrations
      were significantly reduced with AO, resulting in improvement of image resolution.
      In the model eye, image resolution was degraded with increased high-order
      wavefront aberrations (horizontal coma and spherical) and improved with AO
      correction of wavefront error in the presence of increased light scatter. The
      findings of the current study suggest that AO imaging systems can potentially
      improve image resolution in aging eyes with increased aberrations and scatter.

PMID- 17429476
TI  - High-resolution adaptive optics scanning laser ophthalmoscope with dual
      deformable mirrors.
AB  - Adaptive optics scanning laser ophthalmoscopes have been used to produce
      noninvasive views of the human retina. However, the range of aberration
      compensation has been limited by the choice of deformable mirror technology. We
      demonstrate that the use of dual deformable mirrors can effectively compensate
      large aberrations in the human eye while maintaining the quality of the retinal
      imagery. We verified experimentally that the use of dual deformable mirrors
      improved the dynamic range for correction of the wavefront aberrations compared
      with the use of the micro-electro-mechanical-system mirror alone and improved the
      quality of the wavefront correction compared with the use of the bimorph mirror
      alone. We also demonstrated that the large-stroke bimorph deformable mirror
      improved the capability for axial sectioning with the confocal imaging system by
      providing an easier way to move the focus axially through different layers of the
      retina.

PMID- 17429477
TI  - Large-field-of-view, modular, stabilized, adaptive-optics-based scanning laser
      ophthalmoscope.
AB  - We describe the design and performance of an adaptive optics retinal imager that
      is optimized for use during dynamic correction for eye movements. The system
      incorporates a retinal tracker and stabilizer, a wide-field line scan scanning
      laser ophthalmoscope (SLO), and a high-resolution microelectromechanical-systems
      based adaptive optics SLO. The detection system incorporates selection and
      positioning of confocal apertures, allowing measurement of images arising from
      different portions of the double pass retinal point-spread function (psf). System
      performance was excellent. The adaptive optics increased the brightness and
      contrast for small confocal apertures by more than 2x and decreased the
      brightness of images obtained with displaced apertures, confirming the ability of
      the adaptive optics system to improve the psf. The retinal image was stabilized
      to within 18 microm 90% of the time. Stabilization was sufficient for cross
      correlation techniques to automatically align the images.

PMID- 17429478
TI  - Compact multimodal adaptive-optics spectral-domain optical coherence tomography
      instrument for retinal imaging.
AB  - We have developed a compact, multimodal instrument for simultaneous acquisition
      of en face quasi-confocal fundus images and adaptive-optics (AO) spectral-domain
      optical coherence tomography (SDOCT) cross-sectional images. The optical system
      including all AO and SDOCT components occupies a 60x60 cm breadboard that can be
      readily transported for clinical applications. The AO component combines a
      Hartmann-Shack wavefront sensor and a microelectromechanical systems-based
      deformable mirror to sense and correct ocular aberrations at 15 Hz with a maximum
      stroke of 4 microm. A broadband superluminescent diode source provides 4 mum
      depth resolution for SDOCT imaging. In human volunteer testing, we observed up to
      an 8 dB increase in OCT signal and a corresponding lateral resolution of <10
      microm as a result of AO correction.

PMID- 17429479
TI  - Improved scanning laser fundus imaging using polarimetry.
AB  - We present a polarimetric technique to improve fundus images that notably
      simplifies and extends a previous procedure [Opt. Lett.27, 830 (2002)]. A
      generator of varying polarization states was incorporated into the illumination
      path of a confocal scanning laser ophthalmoscope. A series of four images,
      corresponding to independent incoming polarization states, were recorded. From
      these images, the spatially resolved elements of the top row of the Mueller
      matrix were computed. From these elements, images with the highest and lowest
      quality (according to different image quality metrics) were constructed, some of
      which provided improved visualization of fundus structures of clinical importance
      (vessels and optic nerve head). The metric values were better for these
      constructed images than for the initially recorded images and better than
      averaged images. Entropy is the metric that is most sensitive to differences in
      the image quality. Improved visualization of features could aid in the detection,
      localization, and tracking of ocular disease and may be applicable in other
      biomedical imaging.

PMID- 17429480
TI  - 3D phase diversity: a myopic deconvolution method for short-exposure images:
      application to retinal imaging.
AB  - 3D deconvolution is an established technique in microscopy that may be useful for
      low-cost high-resolution imaging of the retina. We report on a myopic 3D
      deconvolution method developed in a Bayesian framework. This method uses a 3D
      imaging model, a noise model that accounts for both photon and detector noises, a
      regularization term that is appropriate for objects that are a mix of sharp edges
      and smooth areas, a positivity constraint, and a smart parameterization of the
      point-spread function (PSF) by the pupil phase. It estimates the object and the
      PSF jointly. The PSF parameterization through the pupil phase constrains the
      inversion by dramatically reducing the number of unknowns. The joint
      deconvolution is further constrained by an additional longitudinal support
      constraint derived from a 3D interpretation of the phase-diversity technique.
      This method is validated by simulated retinal images.

PMID- 17429481
TI  - Automated identification of cone photoreceptors in adaptive optics retinal
      images.
AB  - In making noninvasive measurements of the human cone mosaic, the task of labeling
      each individual cone is unavoidable. Manual labeling is a time-consuming process,
      setting the motivation for the development of an automated method. An automated
      algorithm for labeling cones in adaptive optics (AO) retinal images is
      implemented and tested on real data. The optical fiber properties of cones aided
      the design of the algorithm. Out of 2153 manually labeled cones from six
      different images, the automated method correctly identified 94.1% of them. The
      agreement between the automated and the manual labeling methods varied from 92.7%
      to 96.2% across the six images. Results between the two methods disagreed for
      1.2% to 9.1% of the cones. Voronoi analysis of large montages of AO retinal
      images confirmed the general hexagonal-packing structure of retinal cones as well
      as the general cone density variability across portions of the retina. The
      consistency of our measurements demonstrates the reliability and practicality of
      having an automated solution to this problem.

PMID- 17429482
TI  - Photoreceptor counting and montaging of en-face retinal images from an adaptive
      optics fundus camera.
AB  - A fast and efficient method for quantifying photoreceptor density in images
      obtained with an en-face flood-illuminated adaptive optics (AO) imaging system is
      described. To improve accuracy of cone counting, en-face images are analyzed over
      extended areas. This is achieved with two separate semiautomated algorithms: (1)
      a montaging algorithm that joins retinal images with overlapping common features
      without edge effects and (2) a cone density measurement algorithm that counts the
      individual cones in the montaged image. The accuracy of the cone density
      measurement algorithm is high, with >97% agreement for a simulated retinal image
      (of known density, with low contrast) and for AO images from normal eyes when
      compared with previously reported histological data. Our algorithms do not
      require spatial regularity in cone packing and are, therefore, useful for
      counting cones in diseased retinas, as demonstrated for eyes with Stargardt's
      macular dystrophy and retinitis pigmentosa.

PMID- 17429483
TI  - Adaptive optics-optical coherence tomography: optimizing visualization of
      microscopic retinal structures in three dimensions.
AB  - Adaptive optics-optical coherence tomography (AO-OCT) permits improved imaging of
      microscopic retinal structures by combining the high lateral resolution of AO
      with the high axial resolution of OCT, resulting in the narrowest three
      dimensional (3D) point-spread function (PSF) of all in vivo retinal imaging
      techniques. Owing to the high volumetric resolution of AO-OCT systems, it is now
      possible, for the first time, to acquire images of 3D cellular structures in the
      living retina. Thus, with AO-OCT, those retinal structures that are not visible
      with AO or OCT alone (e.g., bundles of retinal nerve fiber layers, 3D mosaic of
      photoreceptors, 3D structure of microvasculature, and detailed structure of
      retinal disruptions) can be visualized. Our current AO-OCT instrumentation uses
      spectrometer-based Fourier-domain OCT technology and two-deformable-mirror-based
      AO wavefront correction. We describe image processing methods that help to remove
      motion artifacts observed in volumetric data, followed by innovative data
      visualization techniques [including two-dimensional (2D) and 3D representations].
      Finally, examples of microscopic retinal structures that are acquired with the
      University of California Davis AO-OCT system are presented.

PMID- 17429484
TI  - Texton-based segmentation of retinal vessels.
AB  - With improvements in fundus imaging technology and the increasing use of digital
      images in screening and diagnosis, the issue of automated analysis of retinal
      images is gaining more serious attention. We consider the problem of retinal
      vessel segmentation, a key issue in automated analysis of digital fundus images.
      We propose a texture-based vessel segmentation algorithm based on the notion of
      textons. Using a weak statistical learning approach, we construct textons for
      retinal vasculature by designing filters that are specifically tuned to the
      structural and photometric properties of retinal vessels. We evaluate the
      performance of the proposed approach using a standard database of retinal images.
      On the DRIVE data set, the proposed method produced an average performance of
      0.9568 specificity at 0.7346 sensitivity. This compares well with the best
      published results on the data set 0.9773 specificity at 0.7194 sensitivity [Proc.
      SPIE5370, 648 (2004)].

PMID- 17429485
TI  - Simultaneous structural and functional imaging of the macula using combined
      optical coherence tomography ophthalmoscope and multifocal electroretinogram.
AB  - Multimodal imaging (MMI) is a new imaging technique that combines an
      electrophysiological test (multifocal electroretinogram) with an optical
      coherence tomography ophthalmoscope. MMI allows the two technologies to operate
      simultaneously yet independently to provide accurate correlation of macular
      structure and function at multiple sites. Preliminary work with MMI in patients
      with macular holes showed that functional deficits existed beyond the
      geographical area of structural alterations and that macular hole size did not
      always correlate with the severity of functional loss. Functional information may
      therefore be important when assessing prognosis in these patients. We envisage
      that MMI may prove a useful new tool in the assessment of many macular
      pathologies.

PMID- 17429486
TI  - Gaze-contingent display for retinal function testing by scanning laser
      ophthalmoscope.
AB  - To overcome the inconvenience and imprecision of conventional software performing
      microperimetry with the scanning laser ophthalmoscope (SLO) in clinical settings,
      we developed a "smart microperimetry" program. It takes advantage of modern
      computer technology, especially processing speed and high rate of data transfer.
      It allows continuous on-line processing of the image of the retina and
      instantaneous correction of stimulus placement according to involuntary eye
      movements. Thus, the program provides gaze-contingent display of the stimulus and
      senses the conditions for image tracking so that stimulation during large eye
      movements, blinks, and temporarily flawed image quality can be prevented. These
      features have greatly increased the efficiency and precision of SLO data in
      comparison with those obtained by older programs.

PMID- 17429487
TI  - Recombinant adeno-associated virus targets passenger gene expression to cones in
      primate retina.
AB  - Recombinant adeno-associated virus (rAAV) is a promising vector for gene therapy
      of photoreceptor-based diseases. Previous studies have demonstrated that rAAV
      serotypes 2 and 5 can transduce both rod and cone photoreceptors in rodents and
      dogs, and it can target rods, but not cones in primates. Here we report that
      using a human cone-specific enhancer and promoter to regulate expression of a
      green fluorescent protein (GFP) reporter gene in an rAAV-5 vector successfully
      targeted expression of the reporter gene to primate cones, and the time course of
      GFP expression was able to be monitored in a living animal using the RetCam II
      digital imaging system.

PMID- 17429489
TI  - Relating retinal nerve fiber thickness to behavioral sensitivity in patients with
      glaucoma: application of a linear model.
AB  - Glaucoma causes damage to the retinal ganglion cells and their axons, and this
      damage can be detected with both structural and functional tests. The purpose of
      this study was to better understand the relationship between a structural measure
      of retinal nerve fiber layer (RNFL) and the most common functional test,
      behavioral sensitivity with static automated perimetry (SAP). First, a linear
      model, previously shown to describe the relationship between local visual evoked
      potentials and SAP sensitivity, was modified to predict the change in RNFL as
      measured by optical coherence tomography. Second, previous work by others was
      shown to be consistent with this model.

PMID- 17429488
TI  - Adaptive optics scanning laser ophthalmoscopy for in vivo imaging of lamina
      cribrosa.
AB  - The lamina cribrosa has been postulated from in vitro studies as an early site of
      damage in glaucoma. Prior in vivo measures of laminar morphology have been
      confounded by ocular aberrations. In this study the lamina cribrosa was imaged
      after correcting for ocular aberrations using the adaptive optics scanning laser
      ophthalmoscope (AOSLO) in normal and glaucomatous eyes of rhesus monkeys. All
      measured laminar morphological parameters showed increased magnitudes in
      glaucomatous eyes relative to fellow control eyes, indicating altered structure.
      The AOSLO provides high-quality images of the lamina cribrosa and may have
      potential as a tool for early identification of glaucoma.

PMID- 17429490
TI  - Imaging polarimetry and retinal blood vessel quantification at the epiretinal
      membrane.
AB  - We evaluated a polarimetry method to enhance retinal blood vessels masked by the
      epiretinal membrane. Depolarized light images were computed by removing the
      polarization retaining light reaching the instrument and were compared with
      parallel polarized light images, average reflectance images, and the
      corresponding images at 514 nm. Contrasts were computed for retinal vessel
      profiles for arteries and veins. Contrasts were higher in the 514 nm images in
      normal eyes but higher in the depolarized light image in the eyes with epiretinal
      membranes. Depolarized light images were useful for examining the retinal
      vasculature in the presence of retinal disease.

PMID- 17429492
TI  - Automated segmentation of retinal blood vessels and identification of
      proliferative diabetic retinopathy.
AB  - Proliferative diabetic retinopathy can lead to blindness. However, early
      recognition allows appropriate, timely intervention. Fluorescein-labeled retinal
      blood vessels of 27 digital images were automatically segmented using the Gabor
      wavelet transform and classified using traditional features such as area,
      perimeter, and an additional five morphological features based on the derivatives
      of-Gaussian wavelet-derived data. Discriminant analysis indicated that
      traditional features do not detect early proliferative retinopathy. The best
      single feature for discrimination was the wavelet curvature with an area under
      the curve (AUC) of 0.76. Linear discriminant analysis with a selection of six
      features achieved an AUC of 0.90 (0.73-0.97, 95% confidence interval). The
      wavelet method was able to segment retinal blood vessels and classify the images
      according to the presence or absence of proliferative retinopathy.

PMID- 17429491
TI  - Adaptive optics retinal imaging reveals S-cone dystrophy in tritan color-vision
      deficiency.
AB  - Tritan color-vision deficiency is an autosomal dominant disorder associated with
      mutations in the short-wavelength-sensitive- (S-) cone-pigment gene. An
      unexplained feature of the disorder is that individuals with the same mutation
      manifest different degrees of deficiency. To date, it has not been possible to
      examine whether any loss of S-cone function is accompanied by physical disruption
      in the cone mosaic. Two related tritan subjects with the same novel mutation in
      their S-cone-opsin gene, but different degrees of deficiency, were examined.
      Adaptive optics was used to obtain high-resolution retinal images, which revealed
      distinctly different S-cone mosaics consistent with their discrepant phenotypes.
      In addition, a significant disruption in the regularity of the overall cone
      mosaic was observed in the subject completely lacking S-cone function. These
      results taken together with other recent findings from molecular genetics
      indicate that, with rare exceptions, tritan deficiency is progressive in nature.

PMID- 17429493
TI  - Reduced-illuminance autofluorescence imaging in ABCA4-associated retinal
      degenerations.
AB  - The health of the retinal pigment epithelium (RPE) can be estimated with
      autofluorescence (AF) imaging of lipofuscin, which accumulates as a byproduct of
      retinal exposure to light. Lipofuscin may be toxic to the RPE, and its toxicity
      may be enhanced by short-wavelength (SW) illumination. The high-intensity and SW
      excitation light used in conventional AF imaging could, at least in principle,
      increase the rate of lipofuscin accumulation and/or increase its toxicity. We
      considered two reduced-illuminance AF imaging (RAFI) methods as alternatives to
      conventional AF imaging. RAFI methods use either near-infrared (NIR) light or
      reduced-radiance SW illumination for excitation of fluorophores. We quantified
      the distribution of RAFI signals in relation to retinal structure and function in
      patients with the prototypical lipofuscin accumulation disease caused by
      mutations in ABCA4. There was evidence for two subclinical stages of macular
      ABCA4 disease involving hyperautofluorescence of both SW- and NIR-RAFI with and
      without associated loss of visual function. Use of RAFI methods and
      microperimetry in future clinical trials involving lipofuscinopathies should
      allow quantification of subclinical disease expression and progression without
      subjecting the diseased retina/RPE to undue light exposure.

PMID- 17429494
TI  - Imaging polarimetry in patients with neovascular age-related macular
      degeneration.
AB  - Imaging polarimetry was used to examine different components of neovascular
      membranes in age-related macular degeneration. Retinal images were acquired with
      a scanning laser polarimeter. An innovative pseudocolor scale, based on cardinal
      directions of color, displayed two types of image information: relative phases
      and magnitudes of birefringence. Membranes had relative phase changes that did
      not correspond to anatomical structures in reflectance images. Further, membrane
      borders in depolarized light images had significantly higher contrasts than those
      in reflectance images. The retinal birefringence in neovascular membranes
      indicates optical activity consistent with molecular changes rather than merely
      geometrical changes.

PMID- 17429501
TI  - Evaluation of pharmacy students' blood pressure and heart rate measurement skills
      after completion of a patient assessment course.
AB  - OBJECTIVES: To evaluate pharmacy students' skills at measuring brachial artery
      blood pressure and radial heart rate at the completion of a patient assessment
      course in the second-professional year of a doctor of pharmacy (PharmD) program.
      METHODS: Students enrolled in a required patient assessment laboratory course (n
      = 83) participated in this study. Each student was randomly matched with a
      classmate and manually measured the classmate's blood pressure by auscultation of
      the brachial artery and heart rate by palpation of the radial pulse. RESULTS: The
      student-device absolute disagreement was 6.5 +/- 4.8 mmHg for systolic blood
      pressure (SBP), 6.2 +/- 4.5 mmHg for diastolic blood pressure (DBP), and 5.3 +/-
      4.0 beats per minute (BPM) for heart rate. Student and machine measurements of
      SBP, DBP, and HR significantly correlated. CONCLUSIONS: Pharmacy students in the
      second-professional year of a PharmD program demonstrated competence in but not
      mastery of manual blood pressure and heart rate measurement. These skills need
      further refinement during third- and fourth-professional year APPEs.

PMID- 17429495
TI  - Minimalist explicit solvation models for surface loops in proteins.
AB  - We have performed molecular dynamics simulations of protein surface loops
      solvated by explicit water, where a prime focus of the study is the small numbers
      (e.g., ~100) of explicit water molecules employed. The models include only part
      of the protein (typically 500 - 1000 atoms), and the water molecules are
      restricted to a region surrounding the loop. In this study, the number of water
      molecules (N(w)) is systematically varied, and convergence with large N(w) is
      monitored to reveal N(w)(min), the minimum number required for the loop to
      exhibit realistic (fully hydrated) behavior. We have also studied protein surface
      coverage, as well as diffusion and residence times for water molecules as a
      function of N(w). A number of other modeling parameters are also tested. These
      include the number of environmental protein atoms explicitly considered in the
      model, as well as two ways to constrain the water molecules to the vicinity of
      the loop (where we find one of these methods to perform better when N(w) is
      small). The results (for RMSD and its fluctuations for four loops) are further
      compared to much larger, fully solvated systems (using ~10,000 water molecules
      under periodic boundary conditions and Ewald electrostatics), and to results for
      the GBSA implicit solvation model. We find that the loop backbone can stabilize
      with a surprisingly small number of water molecules (as low as 5 molecules per
      amino acid residue). The side chains of the loop require somewhat larger N(w),
      where the atomic fluctuations become too small if N(w) is further reduced. Thus,
      in general, we find adequate hydration to occur at roughly 12 water molecules per
      residue. This is an important result, because at this hydration level,
      computational times are comparable to those required for GBSA. Therefore these
      "minimalist explicit models" can provide a viable and potentially more accurate
      alternative. The importance of protein loop modeling is discussed in the context
      of these, and other, loop models, along with other challenges including the
      relevance of appropriate free energy simulation methodology for assessment of
      conformational stability.

PMID- 17429502
TI  - Self-assessment tool for drug information advanced pharmacy practice experience.
AB  - OBJECTIVE: To describe the use of student self-assessments as a measure of the
      effectiveness of a drug information advanced pharmacy practice experience (APPE)
      and to determine whether other APPEs reinforced information-related skills.
      DESIGN: Students taking a drug information APPE completed a self-assessment
      survey instrument focusing on key information-related skills on the first day and
      again on the last day of that APPE. Findings were used to determine the effect of
      this and other APPEs on perceived information skills. Student ratings were
      compared with faculty ratings for items with similar wording. ASSESSMENT: Student
      self-ratings improved after completing the drug information APPE. Other APPEs,
      gender, and course grade did not significantly impact student perceptions of
      their information-related knowledge and skills. Student and faculty ratings were
      similar, although individual variability occurred. CONCLUSION: Student self
      assessments, along with other direct and indirect data, can provide useful
      information needed to assess and change aspects of the experiential program and
      curriculum.

PMID- 17429503
TI  - An introductory pharmacy practice experience emphasizing student-administered
      vaccinations.
AB  - OBJECTIVE: To introduce a requirement for second-professional year (P2) and third
      professional year (P3) students to administer vaccinations to adults in community
      pharmacy-based immunization clinics. DESIGN: Second-professional year students
      were trained to administer influenza, pneumococcal, and other vaccinations to
      adults following the American Pharmacists Association's standards. All P2
      students in fall 2004 and all P2 and P3 students in fall 2005 were assigned to 2
      community pharmacy-based immunization clinics in the metropolitan Denver area
      under the supervision of immunization-certified staff pharmacists. An evaluation
      of the experience was conducted using retrospective preceptor and student-based
      survey data. ASSESSMENT: In 2004 and 2005, the students administered
      approximately 5,000 (30-50 immunizations per student) and 15,000 (60-70 per
      student) immunizations, respectively. Students and preceptors agreed that the
      requirement to administer vaccinations was an appropriate activity for students
      and that it increased the students' self-confidence. When asked to rate the value
      of the students' work administering adult immunizations in the fall 2004
      semester, the mean score given by the P2 students' immunization-certified
      preceptors was 9.2 on a 10-point Likert scale (1 = no value and 10 = great
      value). CONCLUSION: Consistent with accreditation standards for students to have
      direct patient care responsibilities in introductory pharmacy practice experience
      courses, a requirement for P2 and P3 students to administer vaccines to adult
      patients in community pharmacies was successfully introduced.

PMID- 17429504
TI  - Mental health and psychiatric pharmacy instruction in US colleges and schools of
      pharmacy.
AB  - OBJECTIVES: To describe the extent of psychiatric pharmacy instruction in US
      pharmacy curricula, including course and faculty characteristics and mental
      health topics taught in clinical therapeutics-based courses. METHODS: An 11-item
      survey instrument (54% response) was developed and mailed to 91 colleges and
      schools of pharmacy. RESULTS: Over 75% of colleges and schools employed a
      psychiatric pharmacist; however, less than 50% of faculty teaching psychiatric
      pharmacy content were psychiatric pharmacy specialists as defined in the study.
      All colleges and schools included psychiatric topics as part of a therapeutics
      based course with an average of 9.5% of course content devoted to these topics.
      About 25% of colleges and schools offered elective didactic courses in
      psychiatric pharmacy. Only 2 schools required a psychiatric pharmacy advanced
      pharmacy practice experience (APPE), but about 92% offered elective APPEs. The
      mean number of hours spent on lecture- and case-based instruction across all
      colleges and schools was highest for depression and lowest for personality
      disorders. CONCLUSIONS: There is a need for colleges and schools of pharmacy to
      better identify and standardize the minimal acceptable level of didactic
      instruction in psychiatric pharmacy as well as the minimal level of specialty
      qualifications for faculty members who teach this subject.

PMID- 17429505
TI  - Preadmission predictors of PharmD graduates' performance on the NAPLEX.
AB  - OBJECTIVES: To identify prepharmacy variables that predicted graduate performance
      on the North American Pharmacist Licensure Examination (NAPLEX) test. METHODS:
      Undergraduate and pharmacy school transcripts for 424 students admitted to the
      Texas Tech University Health Sciences Center (TTUHSC) Doctor of Pharmacy program
      from the fall of 1996 to the fall of 2001 were reviewed. NAPLEX scores were
      provided by the Texas State Board of Pharmacy (TSBP). Statistical analyses were
      performed using SPSS, 11.5. RESULTS: Grade point average, composite Pharmacy
      College Admission Test (PCAT) score, and California Critical Thinking Skills Test
      (CCTST) score were each positively correlated with NAPLEX score (p < 0.001 for
      each). Type of school where organic chemistry was completed; age; advanced
      courses taken in chemistry, biology, and math; and attainment of a BS, BA, or MS
      degree were not significantly correlated with NAPLEX score (p > 0.05). When
      comparing students who successfully graduated and passed the NAPLEX with students
      who were academically suspended or who failed the NAPLEX, there were significant
      differences in mean PCAT scores, CCTST score, and age (p < 0.05 for all).
      Stepwise regression analysis applying all admission variables except PCAT
      subscores revealed a correlation between predictors (composite PCAT, prepharmacy
      GPA, and age) and NAPLEX score (p < 0.001). CONCLUSION: Composite PCAT score was
      the strongest predictor of success and failure on the NAPLEX. However, the
      combined predictive ability of PCAT and CCTST scores, prepharmacy GPA, and age
      was relatively low. Thus, a full review of each candidate's application is
      justified.

PMID- 17429506
TI  - Pharmacy students' perceptions of a teaching evaluation process.
AB  - OBJECTIVE: To assess PharmD students' perceptions of the usefulness of Duquesne
      University's Teaching Effectiveness Questionnaire (TEQ), the instrument currently
      employed for student evaluation of teaching. METHODS: Opinions of PharmD students
      regarding the TEQ were measured using a survey instrument comprised of Likert
      type scales eliciting perceptions, behaviors, and self-reported biases. RESULTS:
      PharmD students viewed student evaluation of teaching as appropriate and
      necessary, but conceded that the faculty members receiving the best evaluations
      were not always the most effective teachers. Most students indicated a
      willingness to complete the TEQ when given the opportunity but expressed
      frustration that their feedback did not appear to improve subsequent teaching
      efforts. CONCLUSION: The current TEQ mechanism for student evaluation of teaching
      is clearly useful but nevertheless imperfect with respect to its ability to
      improve teaching. Future research may examine other aspects of pharmacy students'
      roles as evaluators of teaching.

PMID- 17429507
TI  - Where does homeopathy fit in pharmacy practice?
AB  - Homeopathy has been the cause of much debate in the scientific literature with
      respect to the plausibility and efficacy of homeopathic preparations and
      practice. Nonetheless, many consumers, pharmacists, physicians, and other health
      care providers continue to use or practice homeopathic medicine and advocate its
      safety and efficacy. As drug experts, pharmacists are expected to be able to
      counsel their patients on how to safely and effectively use medications, which
      technically includes homeopathic products. Yet many pharmacists feel that the
      homeopathic system of medicine is based on unscientific theories that lack
      supporting evidence. Since consumers continue to use homeopathic products, it is
      necessary for pharmacists to have a basic knowledge of homeopathy and to be able
      to counsel patients about its general use, the current state of the evidence and
      its use in conjunction with other medications.

PMID- 17429508
TI  - A structured approach for teaching students to counsel self-care patients.
AB  - OBJECTIVES: To determine whether the use of a structured interviewing framework
      improved students' ability to treat self-care patients. DESIGN: First
      professional year pharmacy students (P1) in their first quarter of Pharmacy
      Practice Skills Development were taught self-care through a series of 4 modules.
      In each module students' content knowledge and application were assessed using
      quizzes and role-play scenarios, respectively. During the second module, a
      structured interview model (QuEST process) was presented by the instructor and
      students were tested on the same content and role-play used in module 1.
      ASSESSMENT: Sixty-four students completed the 4 self-care modules. Quiz scores
      improved from the first to the second module (75.8% vs. 88.4%, p < 0.001). Mean
      role-play scores also significantly improved after learning the QuEST process.
      CONCLUSION: The QuEST process is an effective tool to teach students how to
      counsel patients with self-care issues.

PMID- 17429509
TI  - A service-learning elective to promote enhanced understanding of civic, cultural,
      and social issues and health disparities in pharmacy.
AB  - OBJECTIVES: To evaluate the effectiveness and impact of an elective service
      learning course offered in cooperation with a charitable pharmacy providing
      services to the surrounding community. METHODS: The 33 students enrolled in the
      service-learning elective were given a 23-question preservice survey instrument
      and a 32-question postservice survey instrument. The survey instruments were
      designed to measure change in the students' perceived knowledge and understanding
      regarding civic, cultural, and social issues and health disparities. RESULTS:
      Significant differences in responses on the presurvey and postsurvey instruments
      suggested changes in students' attitudes and perceptions about the patients and
      the community in which they serve. CONCLUSIONS: Results of the survey indicated
      that by exposing students to issues affecting individuals and the community
      during this elective, a positive change in the student's perception of their
      knowledge and understanding of broader issues facing the community was observed.
      Service-Learning courses provide additional opportunities for students to develop
      as competent, engaged, and caring health care professionals.

PMID- 17429510
TI  - Good teaching is good science.

PMID- 17429511
TI  - Pharmacy is a science-based profession.

PMID- 17429512
TI  - An online debate series for first-year pharmacy students.
AB  - OBJECTIVES: This article describes an online debate series that was developed as
      a new component to an introductory core course for first-professional year
      pharmacy students. Objectives were to facilitate the group process, introduce
      controversial issues related to the US healthcare system, improve critical
      thinking and communication skills, enable students' ability to analyze and
      evaluate evidence, help develop skills in formulating written arguments, and
      encourage tolerance of diverse points of view. DESIGN: One hundred sixty-two
      students were assigned to 40 teams (half assigned to argue as "Pros" and half as
      "Cons") and paired into 20 debating groups. The paired teams posted 3 arguments
      in an online forum alternatively over a 12-week period. The winning teams were
      determined by a panel of 3 judges. ASSESSMENT: Feedback from the judges was
      posted online and summarized in an in-class discussion. Thematic analysis of
      qualitative data from students and faculty members demonstrated the effectiveness
      of the online debate component in helping students work together in a group,
      learn alternative sides of complex issues, and write persuasive arguments.
      CONCLUSION: This novel online-debate forum was a feasible teaching and learning
      strategy, which helped pharmacy students improve their communication skills and
      critical thinking, expanded their scope of knowledge, and provided a platform for
      group process.

PMID- 17429513
TI  - A student orientation program to build a community of learners.
AB  - OBJECTIVES: To describe and evaluate a new student orientation program designed
      to lay the foundations for a community of learners. DESIGN: A weeklong
      orientation program structured as the first week of an 18-week fall semester was
      held for the first-professional year class. Each of the activities supported
      program objectives and developed elements of a community of learners. ASSESSMENT:
      Students' reflective portfolios, daily evaluations and final program evaluations
      provided evidence of development of a community of learners. Positive student
      observations included the use of technology, a discussion of the curriculum and
      experiential education, the use of reflective portfolios, and presentations from
      pharmacy practitioners. Students also appreciated becoming acquainted with the
      faculty, staff, and their peers in a non-threatening atmosphere. Some of the
      aspects rated as least helpful were the learning styles exercise, library tour,
      history of pharmacy session, and the overall length of the orientation. SUMMARY:
      A model for a new student orientation program that builds the foundations for the
      development of a community of learning, which is vital to preparing students to
      provide pharmaceutical care in interdisciplinary teams and become critical
      thinkers, was successfully established. This model could be implemented at other
      schools of pharmacy.

PMID- 17429514
TI  - Assessing students' metacognitive skills.
AB  - OBJECTIVE: To develop a diagnostic test for assessing cognitive skills related to
      metacognition in a physiology course. METHODS: Cognitive skills believed to be
      related to metacognition (visualizing lecture information and interpreting
      diagrams) were identified in a first-professional year (P1) physiology course and
      test items were constructed for each. Analyses included overall reliability, item
      discrimination, and variance comparisons of 4 groups to assess the effect of
      prior physiology coursework and diagnostic test score level on the first
      examination in physiology. RESULTS: Overall reliability was 0.83 (N = 78). Eighty
      percent of the test items discriminated positively. The average diagnostic test
      scores of students with or without a prior physiology course did not differ
      significantly. Students who scored above the class mean on the diagnostic test
      and who had taken a prior physiology course also had the highest average scores
      on the physiology examination. CONCLUSION: The diagnostic test provided a measure
      of a limited number of skills related to metacognition, and preliminary data
      suggest that such skills are especially important in retaining information.

PMID- 17429515
TI  - Integrating performance assessment, maintenance of competence, and continuing
      professional development of community pharmacists.

PMID- 17429516
TI  - Asynchronous video streaming vs. synchronous videoconferencing for teaching a
      pharmacogenetic pharmacotherapy course.
AB  - OBJECTIVES: To compare students' performance and course evaluations for a
      pharmacogenetic pharmacotherapy course taught by synchronous videoconferencing
      method via the Internet and for the same course taught via asynchronous video
      streaming via the Internet. METHODS: In spring 2005, a pharmacogenetic therapy
      course was taught to 73 students located on Amarillo, Lubbock, and Dallas
      campuses using synchronous videoconferencing, and in spring 2006, to 78 students
      located on the same 3 campuses using asynchronous video streaming. A course
      evaluation was administered to each group at the end of the courses. RESULTS:
      Students in the asynchronous setting had final course grades of 89% +/- 7%
      compared to the mean final course grade of 87% +/- 7% in the synchronous group (p
      = 0.05). Regardless of which technology was used, average course grades did not
      differ significantly among the 3 campus sites. Significantly more of the students
      in the asynchronous setting agreed (57%) with the statement that they could read
      the lecture notes and absorb the content on their own without attending the class
      than students in the synchronous class (23%; chi-square test; p < 0.001).
      CONCLUSIONS: Students in both asynchronous and synchronous settings performed
      well. However, students taught using asynchronous videotaped lectures had lower
      satisfaction with the method of content delivery, and preferred live interactive
      sessions or a mix of interactive sessions and asynchronous videos over delivery
      of content using the synchronous or asynchronous method alone.

PMID- 17429517
TI  - Implementation and refinement of a problem-based learning model: a ten-year
      experience.
AB  - OBJECTIVES: To evaluate the effectiveness of a problem-based learning (PBL) model
      implemented in 1995 at the University of Mississippi School of Pharmacy. DESIGN:
      The third-professional (P3) year curriculum was reoriented from a faculty
      centered model of teaching to a student-centered model of learning. Didactic
      lectures and structured classroom time were diminished. Small student groups were
      organized and a faculty facilitator monitored each group's discussions and
      provided individual student assessments. At the end of each 8-week block,
      students were assessed on group participation, disease and drug content
      knowledge, and problem-solving abilities. Faculty and student input was solicited
      at the end of each year to aid programmatic improvement. In 2000, a formal 5-year
      review of the PBL program was conducted. ASSESSMENT: Recommendations for
      improvement included clarifying course objectives, adopting a peer-review process
      for examination materials, refining the group assessment instruments, and
      providing an opportunity for student remediation after a course was failed. A
      weekly case conference presided over by a faculty content expert was also
      recommended. Ongoing critical evaluation during the following 5-year period was
      provided by graduates of the program, faculty participants, and accreditation
      reviews. CONCLUSION: Over our 10-year experience with a PBL model of P3
      education, we found that although the initial challenges of increased demands on
      personnel and teaching space were easily overcome, student acceptance of the
      program depended on their acknowledgment of the practical benefits of active
      learning and on the value afforded their input on curricular development.

PMID- 17429518
TI  - "Community of learning" in experiential education.

PMID- 17429519
TI  - [Evaluation of first 8 pilot methadone maintenance treatment clinics in China].
AB  - OBJECTIVE: To evaluate the effectiveness of the first eight pilot methadone
      maintenance treatment (MMT) clinics in China. METHODS: A questionnaire survey of
      the clients at the 8 pilot MMT clinics was performed at entry, 6 month and 12
      month follow-up. Drug using behaviors, drug related crime behaviors, and
      relationships in families were compared among at entry, 6 and 12 months follow
      up. RESULTS: There were 585, 609 and 468 clients involved at baseline, 6 month
      and 12 month follow-up surveys, respectively. At entry, 6 month and 12 month
      follow-up, the proportion of clients whose injection of drugs reduced from 69.1%
      to 8.9% and 8.8%, and the frequency of injection in the past month had reduced
      from 90 times per month to 2 times per month. Employment rate increased from
      22.9% to 43.2% and 40.6%, and self-reported criminal behaviors reduced from 20.7%
      to 3.6% and 3.8%. At 12 month follow-up, 65.8% of clients reported a healthy
      family relationship, increased from 46.8% at entry, 95.9% of clients reported
      that they were satisfied with the MMT service. CONCLUSION: Pilot MMT program
      reduced drug use, drug injecting behaviors, drug related criminal behaviors, and
      improved relationship with family members. Therefore, MMT clinic should be
      considered as a platform for providing comprehensive services to drug users.

PMID- 17429520
TI  - [Immunogenicity of a chimeric adenovirus type 5 vector with type 35 fiber
      containing HIV-1 gag in mice].
AB  - OBJECTIVE: To study the immune effect of a chimeric adenovirus type 5 vector with
      type 35 fiber (rAd5/F35) vaccine in BALB/c mice. METHODS: The expression of HIV
      Gag protein was determined using indirect immunofluorescent staining. The
      rAd5/F35-mod.gag vector was injected intramuscularly to mice. The IgG antibody
      was detected by ELISA and CTL response was detected by intracellular cytokine
      stain assay. RESULTS: The rAd5/F35-mod.gag vector could express HIV Gag protein
      in vitro and generate strong HIV-specific immune responses in vivo. But anti-Ad5
      immunity could limit its immunogenicity in vivo. CONCLUSION: The rAd5/F35-mod.gag
      vector can elicit specific CTL response and IgG antibody in animal model. In mice
      with high Ad5 vector-specific immunity, Ad5/F35-mod.gag showed lower level of Gag
      specific CTL and antibody response than in mice without pre-existing adenovirus
      type 5 immunity. The results indicated that fiber exchange alone does not evade
      pre-existing Ad5 immunity.

PMID- 17429521
TI  - [Comparative evaluation of Hebei HIV-1 p24 kit for the detection of human
      immunodeficiency virus].
AB  - OBJECTIVE: To probe into the feasibility of screening anti-HIV compounds by using
      HIV-1 p24 detection kit made by Hebei Medical University. METHODS: The
      sensitivity, reproducibility and efficacy of the Hebei p24 kit were evaluated
      compared with the commercially available Vironostika HIV-1 Antigen Microelisa
      System (Biomerieux). RESULTS: Hebei p24 kit had high sensitivity and good
      reproducibility. In vitro screening demonstrated that there was no statistically
      significant difference (P greater than 0.05) between these two kits in assessing
      anti-HIV compounds. CONCLUSION: Hebei p24 kit could be used as an easily
      affordable alternative method for detection of HIV-1 in screening anti-HIV
      compounds.

PMID- 17429522
TI  - [Difference in the CD4+T lymphocytes activation between long term non-progressors
      and typical progressors of HIV-1 infected patients].
AB  - OBJECTIVE: To investigate the difference in the CD4+T lymphocytes activation
      between long term non progressors (LTNP) and typical progressors (TP) of HIV-1
      infected patients. METHODS: Twenty-four HIV-1 infected patients and 15 heathy
      control adults were tested and flow cytometry was used to detect the activation
      marker CD38 and CD4 count in blood samples taken from the patients and control.
      bDNA method was used to test the virus load in the plasma of patients. RESULTS:
      The activation of CD4+T cells was positively correlated with virus load and
      negatively correlated with CD4 counts. Compared with normal controls, the
      activation of CD4+T cells was obviously increased in TP patients but not
      obviously changed in LTNP patients. CONCLUSION: Compared with healthy controls,
      the activation of CD4+T cells in LTNP did not obviously increase. This maybe
      partially accounts for LTNP patients keeping a good state for a long time.

PMID- 17429523
TI  - [HIV-1 molecular epidemiological survey of drug users in Jiangxi province].
AB  - OBJECTIVE: To investigate HIV-1 molecular epidemiology of drug users in Jiangxi
      Province to analyze epidemic situation, subtype, origin of strain, and variation,
      and to provide information for prevention and control of AIDS. METHODS: Combining
      principles of traditional epidemiology and molecular epidemiology, the authors
      analyzed the epidemiologically related factors, the gene sequences and systematic
      mutation of HIV-1 gene in nine drug users in Jiangxi province. RESULTS: The HIV
      spread through the drug users in Jiangxi not only by injection but also by sexual
      contacts. The main epidemic strain found by sequence analysis was HIV-1 CRF01-AE
      that was closely related to the strain among drug users in Vietnam and Guangxi
      Zhuang Autonomous Region, with the average gene distance of 9.00 +/- 2.27 from
      the Vietnam strain. The origin of strain among drug users in the province was
      entirely the same. CONCLUSION: At present, HIV-1 CRF01-AE strain has spread in
      the whole province among the drug users. Vigorous behavioral interventions should
      be developed in drug users and un-safe sexual behavior population to prevent the
      epidemic.

PMID- 17429524
TI  - [Ultrastructural characteristics of gastric mucosal epithelial cells of AIDS
      patients complicated with chronic gastritis].
AB  - OBJECTIVE: To investigate ultrastructural features of gastric mucosal epithelial
      cells of AIDS patients complicated with chronic gastritis. METHODS: Ten AIDS
      patients with alimentary tract symptoms underwent gastroscopy and biopsy of
      gastric mucosa was performed by random method. All the biopsy specimens were
      examined by electron microscopy. RESULTS: There were swelling, vacuolar
      degeneration and increased density of mitochondria, dissociated ribosomes in the
      cytoplasm, and dilation of rough endoplasmic reticulum and Golgi's apparatus.
      Some gastric mucosal cells were in different stages of apoptosis. The gastric
      mucosal cells of the control subjects with chronic gastritis but without AIDS
      showed swelling of mitochondria to different extents and necrosis of epithelial
      cells. CONCLUSION: Injuries of gastric mucosal epithelial cells of AIDS patients
      complicated with chronic gastritis may be more severe than those seen in the
      control subjects and the mechanism of the more severe injuries is unclear.

PMID- 17429525
TI  - [Effect of Nocardia rubra cell wall skeleton on the growth of HeLa cell line
      infected with HPV].
AB  - OBJECTIVE: To investigate the effects of Nocardia rubra cell wall skeleton (Nr
      CWS) on the HeLa cell line, one of the cell lines of human cervical cancer,
      infected with HPV. METHODS: HPV-infected HeLa (HPV 18-positive cells) cultured in
      vitro were divided into two groups: the experiment group and control group. Nr
      CWS was added to the experiment group and PBS to the control. The growth and
      proliferation of HeLa cells were detected with MTT and flow cytometry technology.
      Inhibitive effect of HeLa transplanted tumor was investigated in Scid mice.
      RESULTS: The growth of HeLa cells in the experimental group was apparently
      decreased compared with that of the control. The results of flow cytometry
      demonstrated that more HeLa cells were transferred into quiescent phase in the
      experimental group than that in the control. While less in the proliferative
      phase, both of the volume and weight of HeLa transplanted tumor with drug-added
      group were less than those of control group. CONCLUSION: The Nocardia rubra cell
      wall skeleton is a potiental growth inhibitor and inducer of apoptosis of
      cervical cancer cells in vitro and may provide a new way in prevention or
      supplementary management of anti-human papilloma virus.

PMID- 17429526
TI  - [Oxidative stress in patients with chronic hepatitis B before and after
      interferon alpha-2b treatment].
AB  - OBJECTIVE: To investigate the impacts of interferon alpha-2b (IFN alpha-2b) on
      the oxidative stress states in the treatment of chronic hepatitis B (CHB) with
      different genotypes. METHODS: Thirty-five patients with chronic hepatitis B and
      18 healthy volunteers as a control were enrolled in this present study. In
      control and patients group, the serum alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST), serum malondialdehyde (MDA) levels, serum total
      antioxidative stress capacity (TAC) were measured spectrophotometrically. After
      the therapy with interferon alpha-2b at the dose of 300 million units via
      intramuscular injection thrice a week for 12 weeks, these parameters were
      measured again in the patient group. The genotypes of hepatitis B virus were
      detected by polymerase chain reaction and hybridization. The effective group was
      defined as the patients with complete response and partial response. RESULTS: The
      elevated concentrations of MDA and impaired levels of TAC in the patients with
      CHB were observed as compared to the healthy controls (P < 0.05 for both). There
      were no significant differences in serum levels of MDA and TAC in CHB patients
      with various genotypes (P > 0.05). The serum levels of MDA after the treatment
      with IFN alpha-2b were significantly lower than the pretreatment levels (P <
      0.05), which even returned to the normal concentration (P > 0.05) in the
      effective group. There were significant increases in the TAC after the IFN alpha
      2b therapy in the effective group. However, the significant differences in the
      TAC levels before and after the INFalpha-2b treatment were not observed in the
      non-responsive group. CONCLUSION: The oxidative stress could be improved with IFN
      alpha-2b treatment of chronic hepatitis B patients. The results suggest that
      antioxidant treatment for chronic hepatitis B patients may help improve the
      effect of anti-virus therapy.

PMID- 17429527
TI  - [Peripheral blood T cell subsets and TH1/TH2 cytokines secretion in children with
      chronic hepatitis C virus infection].
AB  - OBJECTIVE: To determine the cellular immunological abnormalities in children with
      chronic hepatitis C virus infection. METHODS: (1) The quantity of the peripheral
      blood T cell subsets in 16 children with chronic hepatitis C virus infection and
      10 healthy blood donors was detected by FACS. (2) The levels of the TH1/TH2
      cytokines secretion of PBMC in patients and healthy blood donors were detected by
      ELISA. RESULTS: (1) Compared with normal controls, there was no significant
      difference in the percentage of CD4+ cells. The percentage of CD8+ cells was
      significantly higher than that of controls (P < 0.05). The percentage of CD3+
      cells was higher and the ratio of CD4+/CD8+ cells was lower, but the difference
      was not significant (P > 0.05). (2) Compared with the cytokine level of normal
      control, the levels of IFN-gamma, IL-10 and TNF-alpha notably increased (P <
      0.01) while IL-2, IL-4, and IL-12 were not detected in the culture supernatant of
      PBMCs from both normal control and patients. CONCLUSION: There is an imbalance in
      peripheral blood T cell subsets and disturbance in cellular immunity in children
      with chronic hepatitis C virus infection, which may be associated with HCV
      persistent infection.

PMID- 17429528
TI  - [Hepatitis E virus infection in population of non-remunerate blood donors in
      Shaoxing].
AB  - OBJECTIVE: To investigate the incidence of HEV infection in population of non
      remunerate blood donors in Shaoxing. METHODS: Blood specimens from 3701 non
      remunerate blood donors were collected, ELISA were used to study anti-HEV IgG and
      IgM antibodies, RT-PCR were further used to study HEV RNA in samples from donors
      whose anti-HEV IgM was positive. RESULTS: Anti-HEV IgG positive rate was 29.19%
      (1107/3701), anti-HEV IgM positive rate was 1.35% (50/3701) among non-remunerate
      blood donors in Shaoxin. Six cases were positive for HEV RNA. The positive rate
      was 0.16% (6/3701), and all the 6 cases belonged to HEV genotype 1. Different
      seasons showed no interference on the positive rate of IgG and IgM. CONCLUSION:
      The detecting and studying of HEV infection among donors was important to ensure
      the safety of blood products and blood transfusion.

PMID- 17429529
TI  - [Association between human papillomavirus (HPV) type 16 infection and E6/E7 gene
      variant and the cervical lesions in Beijing].
AB  - OBJECTIVE: To investigate the association between HPV16 infection, E6/E7
      variations and the cervical lesions. METHODS: HPV subtypes were detected by using
      flow-through hybridization technique, E6/E7 gene was extracted from cervical
      lesions in 80 patients with HPV16 infection, PCR amplified, cloned into plasmid
      pMD18-T and sequenced. RESULTS: HPV 16 was the most common type which accounted
      for 33.3% (154/463), the HPV16 infection rates increased with the severity of
      cervical lesions (P < 0.05). Totally in 72 cases the complete E6 and E7 regions
      were successfully sequenced, the DNA mutation rate of E6/E7 was 88.9% (64/72). A
      mutation, E6-D32E (T96G) coincided with a specific type of E7 mutation, N29S
      (A86G). D32E/N29S mutation rate was 38.9% (28/72), the detection rate increased
      with the severity of cervical lesions (P < 0.05). CONCLUSION: HPV 16 was the most
      common type in women with cervical lesions in Beijing, D32E/N29S variant
      associated with the cervical lesions.

PMID- 17429530
TI  - [Relationship among pathological changes in Liver tissues and level of serum HBV
      DNA, HBeAg and ALT of 194 patients with chronic hepatitis B].
AB  - OBJECTIVE: To study the relationships among pathological and immunohistochemical
      changes in liver tissues, and the HBeAg, HBV DNA, ALT level in the patients with
      chronic hepatitis B. METHODS: Pathological and immunohistochemical examinations
      of liver tissue liver function tests, serum HBV and HBV DNA detection were
      performed in 194 patients with chronic hepatitis B. RESULTS: There was
      significant difference between the serum HBeAg positive group and the negative
      group in G2, G3-4 S2, S3-4 in liver tissues; The serum HBV DNA level of the
      groups S0 and S1-4, and the hepatic activity index between the groups G0-1 and G2
      4 were significantly different. And the hepatic HBcAg positive group and HBcAg
      negative group were significantly different too. There was no significant
      difference between the HBsAg level in liver tissues as "+" group and the "++ -
      +++" group. The pathological diagnosis as S1 or (and) G2 is respectively 28.57%,
      53.33%, 80.15%, 77.88% among the four groups with normal-mild-moderate-severe
      elevated serum ALT level. CONCLUSION: Serum HBV DNA correlated with HBcAg
      expression in liver tissue; the HBsAg level in liver tissues have no relationship
      with the serum HBV DNA level. The patients with low serum HBV DNA level may have
      high index of hepatic activity and hepatic fibrosis. Asymptomatic carriers and
      patients with low serum ALT level should be encouraged to accept liver biopsy. It
      can determine the degree of liver inflammation and fibrosis and timing of
      treatment.

PMID- 17429531
TI  - [Expression of Toll-like receptors in mononuclear cells from children with acute
      rotavirus diarrhea].
AB  - OBJECTIVE: Rotavirus is the single most common cause of severe dehydrating
      diarrhea in young children worldwide, but the pathogenesis and immunity against
      this disease are not completely understood. A prospective study was conducted to
      assess gene expression of toll-like receptors (TLR) in children with acute
      rotavirus diarrhea. METHODS: Seventy-five children with acute rotavirus diarrhea
      and 38 control children were enrolled in this study from Sep. 2004 to Jan. 2005.
      All the 75 patients had detailed records of clinical characteristics. Rotavirus
      antigen was detected by ELISA from stools. Peripheral blood mononuclear cells
      (PBMC) were separated by Ficoll reagent and RNA was extracted by Trizol. The
      levels of mRNA for five TLRs in PBMC were examined by fluorescent quantitative RT
      PCR. RESULTS: Patients with acute rotavirus infection had elevated mean levels of
      TLR 2, 3, 4, 7, 8 mRNA expressions in PBMC within 3 days since onset of the
      disease, P less than 0.05. But only TLR 2, 3, 8 mRNA levels remained increased in
      patients within 7 or 14 days since onset (P less than 0.05). Mean levels of mRNA
      for TLR 4 in PBMC was higher in patients with more severe diarrhea including
      longer duration of diarrhea, more episodes of diarrhea per day and higher
      severity scores (P less than 0.05). CONCLUSION: Manifold TLR may play roles in
      the start-up and regulation of immune responses in children with acute rotavirus
      diarrhea. These findings will be helpful to further recognize immune response in
      Chinese children with rotavirus diarrhea and, consequently, may provide
      directions and insights that could prove critical to the prevention or treatment
      of this important disease.

PMID- 17429532
TI  - [Expressive features of HBsAg and HBcAg in the livers of chronic hepatitis B and
      its clinical significance].
AB  - OBJECTIVE: To investigate the necessity of detecting on the expressive intensity
      and pattern of HBsAg and HBcAg in the livers of chronic hepatitis B. METHODS:
      HBsAg and HBcAg were detected in paraffin-embedded liver tissue by EnVision
      immunohistochemistry. Serum hepatitis B virus DNA (HBV DNA) was tested by real
      time quantitative polymerase chain reaction. The degrees of hepatic inflammatory
      activity (grade) and fibrosis (stage) of liver biopsies were determined according
      to the standard of the Chinese program of prevention and treatment of viral
      hepatitis. RESULTS: The expression of HBsAg was not correlated with the grade,
      the stage and the levels of serum HBV DNA (P > 0.05). Liver HBcAg expressive
      intensity was not correlated with the grade (r=0.02, P > 0.05), while negatively
      correlated with the stage (r=0.28, P < 0.01) and positively correlated with the
      serum HBV DNA levels (r=0.53, P < 0.01). Liver HBcAg expressive pattern was
      negatively correlated with the grade (r=-0.27, P < 0.01). The grade in
      cytoplasmic pattern group was higher than in nuclear pattern group and in mixed
      pattern group (P < 0.01), and that in mixed pattern group was higher in nuclear
      pattern group (P < 0.01). Liver HBcAg expressive pattern was negatively
      correlated with the stage (r=-0.23, P < 0.01). The stage in cytoplasmic pattern
      group was higher than in nuclear pattern group and in mixed pattern group (P <
      0.05). Liver HBcAg expressive pattern was positively correlated with the levels
      of serum HBV DNA (r=0.22, P < 0.01). CONCLUSION: Distinguishing the expressive
      intensity and pattern of HBsAg and HBcAg in the liver of chronic hepatitis B may
      not help understand the degree of hepatic lesion. The detection of HBcAg in liver
      tissue of CHB may be beneficial for the antiviral therapy.

PMID- 17429533
TI  - [Effect of 2-phenoxyethanol on potency of Sabin inactivated poliomyelitis vaccine
      and its safety].
AB  - OBJECTIVE: To investigate the effect of 2-phenoxyethanol on potency of Sabin
      inactivated poliomyelitis vaccine (IPV). METHODS: Sabin IPV samples containing 5
      mg or 7 mg 2-phenoxyethanol each dosage respectively were placed separately at 4
      degrees C, 37 degrees C for 2 days and 7 days. D-antigen contents were tested
      with ELISA method. Then neutralizing antibodies in mice and guinea pigs were
      detected. The safety experiment was performed according to unusual toxicity test
      of China requirement for biological product. RESULTS: After addition of 2
      phenoxyethanol, the I, II, and III D-antigen contents of Sabin IPV did not
      change. The antibody levels in mice and guinea pigs were not different between
      experimental group and control group. Animals were safe during observation
      period. CONCLUSION: 2-Phenoxyethanol had no effect on potency and safety of Sabin
      IPV. It can be used as antiseptic for Sabin IPV.

PMID- 17429534
TI  - [Screening and identification of proteins interacting with HCV NS4A via yeast
      double hybridization in leukocytes and gene cloning of the interacting protein].
AB  - OBJECTIVE: To screen proteins interacting with HCV NS4A protein in leukocytes by
      yeast-double hybridization. METHODS: The bait plasmid pGBKT7-NS4A was transformed
      into yeast AH109 was transformed, and the expressing of the fusion protein was
      identified by SDS-page. The transformed yeast was mated with yeast Y187
      containing leukocytes cDNA library plasmid in 2xYPDA medium. Diploid yeast was
      plated on synthetic dropout nutrient medium (SD/-Trp-Leu-His-Ade) and synthetic
      dropout nutrient medium (SD/-Trp-Leu-His-Ade) containing x-alpha-gal for
      selecting two times and screening. After extracting and sequencing of plasmid
      from blue colonies, analysis was conducted by bioinformatics. And, the gene
      encoding the interesting protein was cloned, and back-cross was performed.
      RESULTS: Forty-five colonies were sequenced, among them, 29 colonies were human
      calcium modulating cyclophilin ligand (CAML). The gene encoding CAML was cloned,
      and the interaction between NS4A and CAML was ensured. CONCLUSION: Seven kinds of
      proteins interacting with NS4A in leukocytes were successfully screened and the
      results brought some new clues for studying the pathogenesis of HCV.

PMID- 17429535
TI  - [Expression of the P1B, P2A, P3AB and P3D protein of hepatitis A virus in
      prokaryotic cell and antigenicity analysis].
AB  - OBJECTIVE: To express P1B, P2A, P3AB and P3D cDNA gene fragments in prokaryotic
      system using thioredoxin fusion expression system; to investigate the
      antigenicity and application of recombinant protein. METHODS: By using PCR
      technique, P1B, P2A, P3AB and P3D gene fragments were cloned. Choosing M47 as the
      expressive vector, the recombinant plasmid P1B, P2A, P3AB and P3D was constructed
      and expressed in Escherichia coli after inducing by IPTG. By anion exchange and
      affinity chromatography, purified recombinant protein was obtained. By using
      Western Blot analysis and indirect ELISA to detect its antigenic activity.
      RESULTS: Four recombinant plasmids was proved to be constructed successfully by
      sequencing and the correct molecular weight of their expression products.
      Recombinant proteins were obtained in BL21 (DE3) and purified after Ni2+ affinity
      chromatography. Western Blot analysis and indirect ELISA showed that P2a had
      specific antigenicity. CONCLUSION: The P2a protein expressed in prokaryotic
      system was proved to have specific antigenicity. The indirect ELISA distinguished
      24 positive sera from 24 negative sera. It is very likely that P2a can be an
      antigen to diagnose acute patients of hepatitis A and differentiate inactivated
      vaccine-induced immunity from an infection.

PMID- 17429536
TI  - [Expression of hepatitis delta antigen Inner Mongolian strain in prokaryotic cell
      and analysis of its antigenicity].
AB  - OBJECTIVE: To obtain high yield and good antigenic activity of HDV L-Ag and to
      detect different regional patients' sera to test the purified antigen's
      antigenicity. METHODS: Hepatitis delta virus' sequence was obtained from Inner
      Mongolian patient by using RT-PCR and PCR methods, PET43a was used and His-tag
      was added at the HDV L-Ag 5' and 3' to construct the recombinant expression
      plasmid, transform the plasmid into host bacterium BL21 and induce it with IPTG.
      The expression supernatant was purified by saturated (NH4)2SO4 and affinity
      chromatography. The activity and antigenicity of the expressed product were
      analyzed by using EIA. RESULTS: Comparison of results obtained with detection by
      using the expressed protein coated plate and ABBOTT Murex anti-Delta (total) of
      15 positive and 10 negative sera, the consistency was good (100%). CONCLUSION:
      EIA proved that the purified antigen had good antigenicity, no serological
      difference was found in detection between different region's sera, therefore the
      purified delta antigen may be useful in diagnostic and other research.

PMID- 17429537
TI  - [A clinical study on combined serum hepatic fibrosis-related markers and
      ultrasound parameters to diagnose hepatic fibrosis].
AB  - OBJECTIVE: This study attempted to explore the value of combining serum hepatic
      fibrosis-related markers and ultrasound parameters together on diagnosis of
      hepatic fibrosis. METHODS: Six serum markers and 8 ultrasound parameters were
      measured from 100 patients with chronic hepatitis B or cirrhosis. The results of
      the serum hepatic fibrosis-related markers and ultrasound in disease group were
      analyzed and compared with the findings of hepatic pathology. RESULTS: By
      filtrating,the group of platelet derived growth factor-BB (PDGF-BB) plus
      hyaluronic acid (HA) plus echo characteristics of liver parenchyma (LPEC) plus
      length of spleen (SL) had the highest Se and Spe, which were 90.7% and 85.4%
      respectively. CONCLUSION: The advantageous combination of serum markers and
      ultrasound parameters can significantly improve Se and Spe, which is superior to
      any single serum index or ultrasound parameter. And it was a better non-invasive
      method for diagnosing hepatic fibrosis.

PMID- 17429538
TI  - [Evaluation of the ELISA diagnostic kits for hepatitis E virus antibody in the
      reference serum, the suspect patients of hepatitis E and normal persons' sera].
AB  - OBJECTIVE: To evaluate the quality of the ELISA diagnostic kits for detecting
      hepatitis E virus (HEV) specific IgG antibody. METHODS: Five diagnostic kits (WT,
      GD, HM, GeneLabs and KH) for anti-HEV IgG were assayed by detecting HEV IgG in
      the HEV diagnostic reference sera from 24 positive cases and 30 negative cases.
      42 cases clinical suspect patients with hepatitis E from Ditan hospital in
      Beijing in 1994 to 1995 and 230 normal persons' sera from Chengdu city, Sichuan
      province in September in 2005. RESULTS: The conformity rates of positive and
      negative sera was 95.83% (23) and 96.67% (29) for WT kit, 87.50% (21) and 100%
      (30) for GD kit, 87.50% (21) and 96.67% (29) for HM kit, 66.67% (16) and 100%
      (30) for GeneLabs kit, 45.83% (11) and 100% (30) for KH kit for detecting anti
      HEV positive and negative reference sera, respectively. The five kits were used
      to detect anti-HEV IgG among 42 clinical suspect patients with hepatitis E and
      230 normal persons' sera, The positive rate was 97.62% (41) and 31.74% (73) by
      WT, 100% (42) and 17.39% (40) by GD kit, 97.62% (41) and 23.91% (55) by HM kit,
      90.48% (38) and 7.83% (18) by GeneLabs kit, 90.48% (38) and 3.48% (8) by KH,
      respectively. CONCLUSION: The positive rates of all the 5 kits were over 90% and
      had a very high conformity in detecting anti-HEV IgG in clinical patient with
      hepatitis E, positive rates of 3.48% to 31.74% were found in detecting the normal
      persons' sera. The research showed insufficiency of the ELISA kits for
      epidemiological survey of HEV infection in population.

PMID- 17429539
TI  - [Comparison of different combination therapies for children with HBeAg positive
      chronic hepatitis B].
AB  - OBJECTIVE: To evaluate the advantages of combination therapy with interferon
      alpha plus nucleoside analogue-lamivudine or HBV vaccine in children with HBeAg
      positive chronic hepatitis B. METHODS: A total of 120 patients with HBeAg
      positive chronic hepatitis B were divided into three groups, 40 patients per
      group. Each group was treated with one of the following therapies respectively:
      Group A IFN-alpha 1b 10 MU/m2 three times per week (Tiw); Group B IFN-alpha 1b
      10MU/m2 three times per week (Tiw) plus lamivudine 3 mg/kg for 6 months. Group C
      IFN-alpha 1b 10 MU/m2 three times per week (Tiw) plus HBV vaccine 30 microg one a
      month. RESULTS: There was no significant difference in normalizing rate of ALT
      among the three groups at end of treatment. There was more significant difference
      in negative rate (seroconversion) of serum HBV DNA and HBeAg in group B than
      group A and group C (P less than 0.05). CONCLUSION: The combination therapy of
      IFN-alpha 1b plus lamivudine seemed to be more effective than the therapy with
      IFN-alpha alone and the combination of IFN-alpha and HBV vaccine.

PMID- 17429540
TI  - [Therapeutic effect of autologous cytokine-induced killer cells on patients with
      liver cirrhosis caused by HBV infection].
AB  - OBJECTIVE: To observe the therapeutic effect of autologous cytokine-induced
      killer cells (CIK) on HBV DNA positive patients with liver cirrhosis. METHODS:
      HBV DNA positive 33 patients with cirrhosis were treated with CIK. Before and
      after cultured in vitro and post-treatment, CD3+, CD3+CD4+, CD3+CD8+, CD3+CD56+
      cells, mDC and pDC were detected by flow cytometry. The indexes of virus and
      liver function were compared between pre- and post-treatment. RESULTS: CD3+,
      CD3+CD8+ cells and CD3+CD56+ cells were higher after cultured in vitro and after
      transfused back than those before culture (91.5 +/- 10.3, 74.4 +/- 9.9 vs. 67.9
      +/- 12.8; 60.9 +/- 15.5, 37.3 +/- 15.1 vs. 27.9 +/- 10.9; 18.4 +/- 11.7, 14.5 +/-
      7.5 vs. 10.6 +/- 7.1). The percentages of mDC and pDC also increased after
      treatment vs. pre-treatment (0.54 +/- 0.18 vs. 0.70 +/- 0.29; 0.26 +/- 0.13 vs.
      0.41 +/- 0.25). HBV DNA became undetectable in 12 patients and decrease exceeded
      100 times in 4 patients after treatment. HBeAg became undetectable in 10 of 14
      patients who were HBeAg positive pretreatment patients, among them 2 patients had
      HBeAb sero conversion. The liver function was improved after treatment. All
      patients tolerated the treatment. CONCLUSION: CIK treatment can increase immune
      effector cells and has some antiviral effect and is safe.

PMID- 17429541
TI  - [Subject diagnostic value of detecting a1pha-fetoprotein variants with a new
      microspincolumn method in hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the usefulness of new microspincolumn method for the
      measurement of a1pha-fetoprotein variant AFP-L3 in differentiation of benign and
      malignant liver disease and the warming for liver cancer. METHODS: AFP-L3 was
      isolated by using microspincolumn coupled with lens culinaris agglutinin (LCA),
      AFP and AFP-L3 were determined with chemiluminescent immunoassay, the proportion
      of AFP-L3 levels AFP-L3(%) were calculated, and the relationship between the
      elevated AFP-L3(%) levels and benign and malignant liver disease was analyzed.
      RESULTS: The levels of AFP-L3(%) in serum of patients with hepatocellular
      carcinoma was significantly higher than those in the patients with other liver
      diseases (P < 0.001). Taking AFP-L3(%) >or= 10% as the diagnostic criteria, the
      sensitivity for diagnosis of liver cancer was 90.9%. CONCLUSION: Detection of AFP
      L3 seemed to be of clinical value in diagnosis and differential diagnosis of
      hepatocellular carcinoma; it may be especially important for identifying patients
      with hepatocellular carcinoma whose a1pha-fetoprotein level is low.

PMID- 17429542
TI  - [Comparative study on detection of hepatitis B virus mutants in precore region
      with two methods].
AB  - OBJECTIVE: To establish a mismatched polymerase chain reaction restricted
      fragment length polymorphism (mPCR-RFLP) method for detection of hepatitis B
      virus (HBV) mutation in precore A1896, and compare with direct sequencing for
      evaluating its applicability. METHODS: According to the principle of mPCR, 194bp
      gene fragments in HBV precore region was amplified. The products of PCR were
      digested by Bsu36I and subjected to agarose gel electrophoresis. A method for
      detecting procore A1896 mutation was established by restricted fragment length
      polymorphism. Totally 134 sera were analyzed by both mPCR-RFLP and direct
      sequencing methods. Two sera which were identified having mixed infection with
      precore wild and mutant strains by mPCR-RFLP also were analyzed by cloning and
      sequencing. RESULTS: From 134 sera, 117 could be analyzed for HBV precore 1896
      situation by mPCR-RFLP method, 109 could be analyzed by sequencing. In 101 sera
      which could be analyzed by the two methods, 54 were mutant strains and 47 were
      wild strains. The results of both methods were completely compatible. There was
      no significant difference in detective rate of HBV precore A1896 mutation between
      the two methods. The sequences of five clones from one serum which was identified
      precore mutant by mPCR-RFLP were all A1896 mutant strains. Another serum was
      identified as mixed infection by mPCR-RFLP, one clone was A1896 mutant strain and
      four were G1896 wild strains. The results of mPCR-RFLP were verified by cloning.
      CONCLUSION: Compared with sequencing, the mPCR-RFLP method is simple, accurate
      and can be used in large-scale surveys and clinical research.

PMID- 17429543
TI  - [Establishment and application of real-time fluorescence quantitative PCR for
      detecting recent thymic output function].
AB  - OBJECTIVE: To establish an accurate and efficient method for detecting recent
      thymic output function and analyze the content of T-cell receptor (TCR)
      rearrangement excision circles (TRECs) within peripheral blood mononuclear cells
      (PBMCs). METHODS: According to the specific sequence of TCRdelta, the primers and
      the fluorescent probe (TaqMan) were designed and synthesized. The standard
      quantitative template was constructed by T/A cloning. The method for detecting
      TRECs was established after optimization of reaction condition, then its
      specificity, sensitivity and stability were tested. Quantitative detection of
      TRECs in DNA of PBMCs from normal individuals and patients of chronic hepatitis B
      were preformed by real-time PCR using TaqMan technique. RESULTS: Detection of
      TRECs was quick and accurate by real-time fluorescence quantitative PCR. The CV
      value of Ct was 1.06%, the product was specific which was confirmed by
      electrophoresis and sequencing and the method showed high sensitivity. The mean
      value of TRECs from normal individuals was (7767.4 +/- 2369.5) copies/10(6)PBMCs
      in healthy controls at age 21.45 but (28,374.4 +/- 7820.4) copies/10(6)PBMCs in
      those at age 16.20 (P < 0.05). The mean value of TRECs from patients with chronic
      hepatitis B was (6480.9 +/- 2031.2) copies/10(6) PBMCs in those at age 21.45,
      which was statistically significant as compared with normal individuals at age
      21.45. CONCLUSION: Real-time fluorescence quantitative PCR for detecting the
      TRECs is an accurate, efficient and stable method and the recent thymic output
      function might decrease in patients with chronic hepatitis B.

PMID- 17429544
TI  - [Expression, purification, and characterization of an anti-human RBC ScFv-HIV
      gp160 fusion protein for hemagglutination-based rapid detection of antibodies to
      HIV in whole blood].
AB  - OBJECTIVE: To construct and express anti-human RBC and HIVgp160 fusion protein
      for rapid detection of antibody to HIV. METHODS: The gene of the anti human RBC
      ScFv and HIV antigen were constructed together into expression vector. The fusion
      protein was expressed in E. coli. RESULTS: The fusion protein was proved to be
      able to bind both anti-RBC and HIVgp160. It could cause agglutination of human
      RBC when HIVgp160 was present. CONCLUSION: The fusion protein has the potential
      in rapid detection of HIV.

PMID- 17429545
TI  - [Experimental studies on treatment of HSV infections with photodynamic therapy
      using 5-aminolevulinic acid].
AB  - OBJECTIVE: To investigate in vitro and in vivo anti-human herpes simplex virus
      effects of photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA). METHODS:
      Guinea pigs model of cutaneous herpes virus infection was applied, and Vero cells
      infected by HSV-I and HSV-II were used as experimental systems to observe the
      antiherpes effect of ALA-PDT. RESULTS: The in vitro experiments showed that ALA
      PDT has antiherpes effect on HSV-I and HSV-II, its effect was similar to that of
      acyclovir. The results of animal experiments showed that ALA-PDT had significant
      therapeutic effect on guinea pigs model of cutaneous herpes virus infection, the
      effect was dose-related. CONCLUSION: ALA-PDT could be effective in treating HSV
      infections, which may provide a new approach to the treatment of viral
      infections.

PMID- 17429546
TI  - Self-assembly of 1-D organic semiconductor nanostructures.
AB  - This review focuses on the molecular design and self-assembly of a new class of
      crowded aromatics that form 1-D nanostructures via hydrogen bonding and pi-pi
      interactions. These molecules have a permanent dipole moment that sums as the
      subunits self assemble into molecular stacks. The assembly of these molecular
      stacks can be directed with electric fields. Depending on the nature of the side
      chains, molecules can obtain the face-on or edge-on orientation upon the
      deposition onto a surface via spin cast technique. Site-selective steady state
      fluorescence, time-resolved fluorescence, and various types of scanning probe
      microscopy measurements detail the intermolecular interactions that drive the
      aromatic molecules to self-assemble in solution to form well-ordered columnar
      stacks. These nanostructures, formed in solution, vary in their number, size, and
      structure depending on the functional groups, solvent, and concentration used.
      Thus, the substituents/side-groups and the proper choice of the solvent can be
      used to tune the intermolecular interactions. The 1-D stacks and their aggregates
      can be easily transferred by solution casting, thus allowing a simple preparation
      of molecular nanostructures on different surfaces.

PMID- 17429547
TI  - Probing dynamics of complex molecular systems with ultrafast 2D IR vibrational
      echo spectroscopy.
AB  - Ultrafast 2D IR vibrational echo spectroscopy is described and a number of
      experimental examples are given. Details of the experimental method including the
      pulse sequence, heterodyne detection, and determination of the absorptive
      component of the 2D spectrum are outlined. As an initial example, the 2D spectrum
      of the stretching mode of CO bound to the protein myoglobin (MbCO) is presented.
      The time dependence of the 2D spectrum of MbCO, which is caused by protein
      structural evolution, is presented and its relationship to the frequency
      frequency correlation function is described and used to make protein structural
      assignments based on comparisons to molecular dynamics simulations. The 2D
      vibrational echo experiments on the protein horseradish peroxidase are presented.
      The time dependence of the 2D spectra of the enzyme in the free form and with a
      substrate bound at the active site are compared and used to examine the influence
      of substrate binding on the protein's structural dynamics. The application of 2D
      vibrational echo spectroscopy to the study of chemical exchange under thermal
      equilibrium conditions is described. 2D vibrational echo chemical exchange
      spectroscopy is applied to the study of formation and dissociation of organic
      solute-solvent complexes and to the isomerization around a carbon-carbon single
      bond of an ethane derivative.

PMID- 17429548
TI  - Reliable structures and energetics for two new delocalized pi...pi prototypes:
      cyanogen dimer and diacetylene dimer.
AB  - Two new prototype delocalized pi[dot dot dot]pi complexes are introduced: the
      dimers of cyanogen, (N[triple bond]C-C[triple bond]N)(2), and diacetylene,
      (HC[triple bond]C-C[triple bond]CH)(2). These dimers have properties similar to
      larger delocalized pi...pi systems such as benzene dimer but are small enough
      that they can be probed in far greater detail with high accuracy electronic
      structure methods. Parallel-slipped and T-shaped structures of both cyanogen
      dimer and diacetylene dimer have been optimized with 15 different procedures. The
      effects of basis set size, theoretical method, counterpoise correction, and the
      rigid monomer approximation on the structure and energetics of each dimer have
      been examined. MP2 and CCSD(T) optimized geometries for all four dimer structures
      are reported, as well as estimates of the CCSD(T) complete basis set (CBS)
      interaction energy for every optimized geometry. The data reported here suggest
      that future optimizations of delocalized pi[dot dot dot]pi clusters should be
      carried out with basis sets of triple-zeta quality. Larger basis sets and the
      expensive counterpoise correction to the molecular geometry are not necessary.
      The rigid monomer approximation has very little effect on structure and
      energetics of these dimers and may be used without consequence. Due to a
      consistent cancellation of errors, optimization with the MP2 method leads to
      CCSD(T)/CBS interaction energies that are within 0.2 kcal mol(-1) of those for
      structures optimized with the CCSD(T) method. Future studies that aim to resolve
      structures separated by a few tenths of a kcal mol(-1) should consider the
      effects of optimization with the CCSD(T) method.

PMID- 17429549
TI  - Low temperature capture of open shell dipolar molecules by ions: the capture of
      rotationally selected NO((2)Pi(1/2), j) by C(+).
AB  - The low-energy capture of dipolar diatomic molecules in an open electronic state
      by ions is usually considered to be induced by the first-order charge-permanent
      dipole interaction with other terms of the long-range potential playing a minor
      role. If the molecular dipole moment is anomalously small (as is the case for
      slightly asymmetrical molecules), however, the situation changes, and the capture
      dynamics is strongly affected by higher orders of the charge-permanent dipole,
      charge-permanent quadrupole, and charge-induced dipole interactions. The
      interplay of different terms in the interaction potential manifests itself in
      complicated temperature dependence of the rotationally state-specific capture
      rate coefficients. These features of the capture are studied by way of example
      for NO(X (2)Pi(1/2), j) + C(+) collisions in the temperature range 10(-2)-20 K
      where the dynamics is adiabatic with respect to rotational and fine-structure
      transitions and sudden with respect to transitions between Lambda doubling and
      hyperfine states. The theoretical rate coefficient, which depends on the
      translational and rotational temperature, agrees with the experimental one
      measured at T(tr) = 0.6 K and T(rot) = 20 K.

PMID- 17429550
TI  - The effects of energy-level resonance on collision-induced electronic energy
      transfer: CD (A (2)Delta<--> B (2)Sigma(-)) coupling.
AB  - Pulsed, time- and wavelength-resolved laser-induced fluorescence spectroscopy has
      been used to measure rate constants for collision-induced electronic energy
      transfer (EET) between the A (2)Delta and B (2)Sigma(-) states of the CD radical.
      EET rate constants in the exothermic direction from B (2)Sigma(-), v = 0 to the
      unresolved A (2)Delta, v = 0 and 1 levels span the range 0.1-2.4 x 10(-11) cm(3)
      s(-1) at room temperature (ca. 295 K) for the partners He, Ar, N(2), CO and
      CO(2). H(2) was also investigated, but was unsuitable for further study because
      of its rapid isotope exchange with CD(X (2)Pi). As expected, only CO results in a
      significant rate of removal on any distinct, unobserved channel, presumed to be
      chemical reaction. The efficient A (2)Delta, v = 1 --> 0 vibrational relaxation
      by CO(2) observed previously for CH was not found for CD. Despite the significant
      differences in their detailed rovibronic level structures, the overall efficiency
      of EET in CD was found to be very similar to that for CH. The positive
      correlation in a Parmenter-Seaver plot appears to confirm a role for long-range
      attractive forces in the EET process. However, the detailed deviations from this
      overall trend found reproducibly for CD and CH suggests that partner-specific
      interactions are also important.

PMID- 17429551
TI  - Rotational spectroscopy of the isotopic species of silicon monosulfide, SiS.
AB  - Pure rotational transitions of silicon monosulfide ((28)Si(32)S) and its rare
      isotopic species have been observed in their ground as well as vibrationally
      excited states by employing Fourier transform microwave (FTMW) spectroscopy of a
      supersonic molecular beam at centimetre wavelengths (13-37 GHz) and by using long
      path absorption spectroscopy at millimetre and submillimetre wavelengths (127-925
      GHz). The latter measurements include 91 transition frequencies for (28)Si(32)S,
      (28)Si(33)S, (28)Si(34)S, (29)Si(32)S and (30)Si(32)S in upsilon = 0, as well as
      5 lines for (28)Si(32)S in upsilon = 1, with rotational quantum numbers J''< or =
      52. The centimetre-wave measurements include more than 300 newly recorded lines.
      Together with previous data they result in almost 600 transitions (J'' = 0 and 1)
      from all twelve possible isotopic species, including (29)Si(36)S and (30)Si(36)S,
      which have fractional abundances of about 7 x 10(-6) and 4.5 x 10(-6),
      respectively. Rotational transitions were observed from upsilon = 0 for the least
      abundant isotopic species to as high as upsilon = 51 for the main species. Owing
      to the high spectral resolution of the FTMW spectrometer, hyperfine structure
      from the nuclear electric quadrupole moment of (33)S was resolved for species
      containing this isotope, as was much smaller nuclear spin-rotation splitting for
      isotopic species involving (29)Si. By combining the measurements here with
      previously published microwave and infrared data in one global fit, an improved
      set of spectroscopic parameters for SiS has been derived which include several
      terms describing the breakdown of the Born-Oppenheimer approximation. With this
      parameter set, highly accurate rotational frequencies for this important
      astronomical molecule can now be predicted well into the terahertz region.

PMID- 17429552
TI  - First-principles calculations of solid-state (17)O and (29)Si NMR spectra of
      Mg(2)SiO(4) polymorphs.
AB  - The nuclear magnetic resonance (NMR) shielding and electric field gradient (EFG)
      tensors of three polymorphs of Mg(2)SiO(4), forsterite (alpha-Mg(2)SiO(4)),
      wadsleyite (beta-Mg(2)SiO(4)) and ringwoodite (gamma-Mg(2)SiO(4)), have been
      calculated using a density functional theory (DFT) approach with a planewave
      basis set and pseudopotential approximation. These Mg(2)SiO(4) polymorphs are the
      principal components of the Earth down to depths of 660 km and have been proposed
      as the hosts of water in the Earth's upper mantle and transition zone. A
      comparison of our calculations with single-crystal spectroscopic data in the
      literature for the alpha-polymorph, forsterite, shows that both the magnitude and
      orientation of the shielding and EFG tensors for O and Si can be obtained with
      sufficient accuracy to distinguish subtle differences in atomic positions between
      published structures. We compare calculated (17)O MAS NMR quadrupolar powder
      lineshapes directly with experimental lineshapes and show that we are able to
      reproduce them within the precision with which the NMR parameters may be
      determined from multi-parameter fitting. The relatively small amounts of sample
      available for the beta- and gamma-polymorphs, arising from the high pressures
      required for synthesis, has hindered the extraction of NMR parameters in previous
      work. The application of DFT calculations to these high-pressure polymorphs
      confirms previous spectral assignments, and provides deeper insight into the
      empirical correlations and observations reported in the literature. These first
      principles methods are highly promising for the determination of local bonding in
      more complex materials, such as the hydrated forms of Mg(2)SiO(4), by aiding
      analysis of their multinuclear NMR spectra.

PMID- 17429553
TI  - Inner-shell spectroscopy by the Gaussian and augmented plane wave method.
AB  - We present an approach for calculating near-edge X-ray absorption spectra at the
      density functional theory level, which is suited for condensed matter
      simulations. The method is based on the standard solution of the all-electron KS
      equations with a modified core-hole potential, which reproduces the relaxation of
      the orbitals induced by the promotion of the core electron to an unoccupied
      valence level. The all-electron description of the charge density is based on the
      Gaussian and augmented plane wave formalism. The reliability of the proposed
      method is assessed by comparing the computed spectra of some small molecules in
      the gas phase to the experimental spectra reported in literature. The sensitivity
      of the computed spectra to the local environment, i.e. the specific bonds formed
      by the absorbing atom or the presence of hydrogen bonds, open promising
      perspective for this technique as a predictive tool in the investigation of a
      more complex system of an unknown structure. The straightforward extension of the
      method to condensed matter is demonstrated by the calculation of the C K-edge in
      diamond.

PMID- 17429554
TI  - Subpicosecond UV spectroscopy of carbonmonoxy-myoglobin: absorption and circular
      dichroism studies.
AB  - A thorough absorption and circular dichroism study is performed in carbonmonoxy
      myoglobin with a sub-picosecond visible pump, ultraviolet probe experiment.
      Differential absorption in the 220-360 nm range shows that the time-resolved
      response mainly comes from the heme and that aromatic amino acids do not
      contribute significantly. Time-resolved CD at 260 nm shows no dynamics and
      confirms this result. On the contrary, a strong CD dynamics is observed at 230
      nm. This signal could originate from transient deformation of the alpha-helices
      in the protein.

PMID- 17429555
TI  - Investigation of complexes formed by interaction of cationic gemini surfactants
      with deoxyribonucleic acid.
AB  - Cationic gemini surfactants, N,N-bis(dimethylalkyl)-alpha,omega-alkanediammonium
      dibromide [C(m)H(2m+1)(CH(3))(2)N(+)(CH(2))(s)N(+)(CH(3))(2)C(m)H(2m+1) x 2 Br(
      ), or m-s-m], have proven to be effective synthetic vectors for gene delivery
      (transfection). Complexes (lipoplexes) of gemini compounds, where m = 12, s = 3,
      12 and m = 18 : 1(oleyl), s = 2, 3, 6, with DNA have been investigated using
      isothermal titration calorimetry (ITC), dynamic light scattering (DLS), zeta
      potential, atomic force microscopy (AFM) and circular dichroism (CD) techniques.
      The results show that lipoplex properties depend on the structural properties of
      the gemini surfactants, the presence of the helper lipid
      dioleoylphosphatidylethanolamine (DOPE), and the titration sequence. ITC data
      show that the interaction between DNA and gemini surfactants is endothermic and
      the observed enthalpy vs. charge ratio profile depends upon the titration
      sequence. Isoelectric points (IP) of lipoplex formation were estimated from the
      zeta potential measurements and show good agreement with the reaction endpoints
      (RP) obtained from ITC. DLS data indicate that DNA is condensed in the lipoplex.
      AFM images suggest that the lipoplex morphology changes from isolated globular
      like aggregated particles to larger-size aggregates with great diversity in
      morphology. This change is further accentuated by the presence of DOPE in the
      lipoplexes. The results are interpreted in terms of some current models of
      lipoplex formation.

PMID- 17429556
TI  - Theoretical and spectroscopic study of the reaction of diethylhydroxylamine on
      silicon(100)-2 x 1.
AB  - Incorporating diversity into structures constructed from the organic modification
      of silicon surfaces requires the use of molecules that contain multiple
      substituents of different types. In this work we examine the possible
      dissociation pathways of diethylhydroxylamine (DEHA, (C(2)H(5))(2)NOH) on the
      surface of clean silicon(100)-2x1 using cluster and planewave computational
      methods and high resolution electron energy loss spectroscopy. Our computational
      results show that DEHA initially forms a strongly-bound complex with the surface
      via a dative N-Si bond. A low-barrier O-H bond scission then occurs yielding a
      surface silicon dimer capped by the (C(2)H(5))(2)NO and H fragments. Calculated
      and measured vibrational spectra support the computed reaction mechanism.

PMID- 17429557
TI  - Do overactive bladder symptoms improve after repair of anterior vaginal wall
      prolapse?
AB  - This study aims to evaluate the changes of overactive bladder symptoms to
      anterior vaginal wall prolapse repair. Ninety-three consecutive women with
      symptomatic anterior vaginal wall prolapse >or= stage II and coexistent
      overactive bladder symptoms were prospectively studied using a urinalysis,
      urodynamics, King's Health Questionnaire (KHQ), Prolapse Quality of Life (P-QOL)
      questionnaire and pelvic organ prolapse quantification (POP-Q) system before and
      1 year after surgery. All women underwent a standard fascial anterior repair.
      Postoperatively, urinary frequency, urgency and urge incontinence disappeared in
      60, 70 and 82% of women respectively (p value < 0.001). The vaginal examination
      findings as well as the quality of life of the women assessed using KHQ and P-QOL
      significantly improved after surgery (p value < 0.001). This study has
      demonstrated that anterior vaginal repair does produce significant improvement in
      overactive bladder symptoms. A larger longer-term study is required to assess if
      these changes persist over time.

PMID- 17429558
TI  - Is anterior genital tract trauma associated with complaints of postpartum urinary
      incontinence?
AB  - We evaluated whether anterior genital trauma is associated with urinary
      incontinence after vaginal birth. A prospective cohort of midwifery patients
      consented to mapping of trauma at birth and assessment of continence postpartum.
      Trauma was categorized into intact, anterior (periuretheral, clitoral, labial),
      perineal or both. Incontinence was defined as a positive response to the
      question, "Since the birth of your baby, have you leaked urine when you did not
      mean to?" and social impact assessed by the Incontinence Impact Questionnaire-7
      (IIQ-7). Of 554 eligible women, 436 (79%) provided incontinence data 3 months
      postpartum. Genital trauma was common, occurring in 80% of women: in 148 (34%)
      trauma was anterior, 119 (27%) had both anterior and perineal trauma and 80(18%)
      had only perineal trauma. Since delivery, 27% (118/436) women leaked urine. Fewer
      had IIQ-7 scores greater than 0, at 55/436 (12%). Women with anterior trauma,
      29/148 (20%), were less likely to complain of incontinence than all others,
      89/288 (31%) (P = 0.01). Urinary incontinence is common after giving birth,
      although most women have mild symptoms. Anterior trauma is not associated with
      increased complaints of urinary incontinence.

PMID- 17429559
TI  - A prospective, randomized controlled trial of the use of an anal purse-string
      suture to decrease contamination during pelvic reconstructive surgery.
AB  - The objective of this study was to evaluate the clinical utility of an anal purse
      string suture to prevent contamination of the operative field during vaginal
      surgery. Patients undergoing vaginal surgery involving the posterior compartment
      were enrolled to receive a purse-string suture closing the anus (group 1) or to
      not receive the suture (group 2). Perineal/perianal cultures were performed after
      sterile preparation and at conclusion of surgery. The primary outcome measure was
      gross fecal contamination. Secondary outcomes were results of perineal cultures.
      Continuous and ordinal variables were compared between groups using Wilcoxon rank
      sum tests, while comparisons of binary variables were performed using exact
      unconditional tests. Forty (40) patients were randomized. There were no
      significant differences in the two groups including age (P = 0.95), parity (P =
      0.40), operative time (P = 0.75), and estimated blood loss (P = 0.81). Gross
      contamination rates were 0/40 (0%) for group 1 and 5/19 (26.3%) for group 2 (P =
      0.015). Contamination by fecal flora occurred in 2/20 (10%) for group 1 and in
      5/20 (25%) for group 2 (P = 0.27). No wound infections, graft erosions, or
      healing abnormalities were noted in either group. An anal purse-string suture is
      an effective way of reducing fecal contamination of the sterile field when
      performing vaginal pelvic reconstructive surgery.

PMID- 17429561
TI  - Minimally invasive mandible reduction using Lee's Rasp & Saw.
AB  - Mandible reduction is one of the most well-known facial contouring procedures
      used to reduce the size of the face for Asian patients, and many studies have
      been conducted. However, these studies have largely included only exposure by the
      intraoral incision, which can be accompanied by serious emergency situations and
      complications. Difficulties in mandible reduction can be encountered during the
      process of maintaining visual sight for the approaching saw. In maintaining the
      visual field, the patient's mouth should be widely stretched while the incision
      and periosteal elevation is extended largely around the entire mandible. This
      occasionally has been related to serious emergency situations such as airway
      obstruction caused by edema and massive bleeding. The authors have tried to solve
      these difficulties with the help of new surgical equipment, which includes a bone
      dust-collecting rasp with simultaneous suction and irrigation known as Lee's Rasp
      & Saw. The "minimally invasive" surgical technique can be used with this new rasp
      and saw. Rasping is performed through a 4- to 6-mm stab incision like other
      endoscope-assisted techniques so soft tissue injury is minimized and the
      operation procedures are simplified. The authors have applied this new surgical
      method to more than 260 male and female patients, and their experience has been
      satisfying in terms of decreased complications and reduced operation times. This
      report describes the external approach only. The authors are evaluating this new
      method using an intraoral approach as well, and the results are as good as those
      for the external approach.

PMID- 17429562
TI  - A new hormonal therapy for estrogen receptor-negative breast cancer.
AB  - BACKGROUND: We postulate that the androgen dehydroepiandrosterone sulfate (DHEAS)
      may represent an innovative hormonal treatment for estrogen (ER), progesterone
      (PR) receptor-negative, but androgen receptor (AR)-positive breast cancers by
      inhibiting breast cancer cell growth through AR stimulation. METHODS: Three ER,PR
      negative breast cancer cell lines (HCC 1137, 1954, and 38), were treated with
      DHEAS. DHEAS-induced growth was measured by a methylthiotetrazole (MTT)
      proliferation assay and apoptosis by TUNEL fluorescence. Androgen receptor gene
      expression levels were determined using quantitative real-time polymerase chain
      reaction (q-RT-PCR). RESULTS: HCC cell lines 1954 and 1937 were positive for AR
      expression; HCC 38 was weakly positive. MTT analysis showed DHEAS-induced
      decreases in cell proliferation of 47% in HCC 1937, 27% in HCC 1954, and 0.4% in
      HCC 38. Ten days of culturing HCC 1954 cells after the removal of DHEAS resulted
      in a 3.5-fold increase in growth. Continuous treatment for the same duration
      induced a 2.8-fold decrease in growth. Parallel experiments showed no significant
      changes in HCC 38 cultures. TUNEL assays showed DHEAS-induced apoptosis fold
      increases of 2.8 in HCC 1937, 1.9 in HCC 1954, and no significant difference in
      HCC 38 cultures. Q-RT-PCR of HCC 1954 cells showed a 6-fold DHEAS-induced
      decrease in AR gene expression at 4 h. Co-treatment with Casodex nullified this
      effect. CONCLUSIONS: DHEAS inhibited growth of ER,PR-negative, AR-positive breast
      cancer cells. DHEAS was cytotoxic to these breast cancer cells via the apoptosis
      pathway. DHEAS may be an effective treatment for a population previously excluded
      from hormone therapy.

PMID- 17429563
TI  - An evidence-based approach to familial nonmedullary thyroid cancer: screening,
      clinical management, and follow-up.
AB  - Approximately 5% of nonmedullary thyroid cancers are of familial origin. When two
      or more family members are diagnosed with nonmedullary thyroid cancer in the
      absence of other known associated syndromes it is termed familial nonmedullary
      thyroid cancer (FNMTC). The genetic inheritance of FNMTC remains unknown, but it
      is believed to be an autosomal dominant mode of inheritance with incomplete
      penetrance and variable expressivity. FNMTC has been shown to be more aggressive
      and to have a worse prognosis than sporadic nonmedullary thyroid cancer. For
      example, studies have demonstrated that individuals with FNMTC have an increased
      risk of multifocal disease, local invasion, and lymph node metastases. These
      aggressive features appear to contribute to the higher recurrence rate and
      decreased disease-free survival seen in FNMTC patients compared to those with
      sporadic differentiated thyroid cancer. This article is an overview of the
      literature available in the English language discussing FNMTC. Critical questions
      regarding the screening, management, and follow-up of these patients are
      addressed with answers proposed based on the available literature. The quality of
      the evidence is ranked according to Sackett's criteria. Overall, the literature
      quality is somewhat limited, based on the low prevalence of FNMTC, the difficulty
      in identifying familial cases, the variable study designs, and limited long-term
      follow-up. CONCLUSIONS: To date, the optimal clinical approach is yet to be
      established, but improved awareness and screening will permit earlier detection,
      more timely intervention, and hopefully improved outcomes for patients and their
      families.

PMID- 17429565
TI  - Portal venous gas detected on computed tomography in emergency situations:
      surgery is still necessary.
AB  - BACKGROUND: Portal venous gas (PVG) has been reported to be associated with
      lethal surgical diagnosis. Recent studies tend to confirm the clinical
      significance of gas in the portal vein; however, some patients are managed
      without surgical treatment. The aim of this study was to assess both the
      diagnoses and the treatment of patients with PVG in an emergency surgical
      setting. MATERIALS AND METHODS: We performed a retrospective chart review of 15
      patients with PVG in the emergency setting detected by computed tomography (CT)
      between July 1999 and July 2004. Characteristics assessed included age, sex,
      clinical presentation, first CT diagnosis of both PVG and the underlying
      pathology, American Society of Anesthesiologists (ASA) score, surgical findings,
      final clinical diagnosis, duration of hospitalization, and evolution of the
      illness/mortality. All patients were examined one month after operation. RESULTS:
      This series of 5 women and 10 men ranged in age from 38 to 90 years at the time
      they underwent emergency surgical treatment. The mean preoperative ASA score was
      4.20. Computed tomography diagnosed the underlying pathology in all cases: bowel
      obstruction (4 cases), bowel necrosis (9 cases), and diffuse peritonitis (2
      cases). The mean length of hospital stay was 12.4 days. The mortality rate was
      46.6%; (7 patients). CONCLUSIONS: A wide range of pathologies can generate PVG.
      Computed tomography can detect both the presence of gas and the underlying
      pathology. In emergency situations, all the diagnosed causal pathologies required
      a surgical procedure without delay. We report that the prognosis was related to
      the pathology itself and was not influenced by the presence of PVG.

PMID- 17429564
TI  - Telomerase activity in tumor and remnant liver as predictor of recurrence and
      survival in hepatocellular carcinoma after resection.
AB  - BACKGROUND AND AIM: Results after curative liver resection in hepatocellular
      carcinoma are unsatisfactory with regard to high postoperative intrahepatic
      recurrence and liver failure. This study evaluates telomerase activity in liver
      with and without tumor as a predictor of recurrence and survival. MATERIALS AND
      METHODS: Liver tissue with and without tumor from 53 hepatocellular carcinoma
      patients receiving curative resection during the period of 1998-2000 was used for
      detecting telomerase activity by PCR-ELISA. Clinicopathological data were
      compared to identify predictors of recurrence and survival. RESULTS: Telomerase
      activity was detected in 98% of liver tissue with tumor and 70% liver tissue
      without. Telomerase activity in cancerous liver correlated significantly with HCV
      infection (P = 0.012) and cirrhotic change in liver parenchyma (P = 0.006).
      Telomerase activity in non-cancerous liver correlated with high serum AFP level
      (P = 0.002). The telomerase activity of liver tissue with and without tumor is
      significant higher in patients with recurrence than in those without recurrence,
      413.7 +/- 100.5 versus 110.8 +/- 32.7, P = 0.006, and 34.7 +/- 14.2 versus 4.2 +/
      1.4, P = 0.039. Recurrence could be predicted by abnormally high tumor
      telomerase activity (P = 0.026) or by advanced TNM stage (P = 0.001). TNM stage
      or high serum ALT level could predict multinodular intrahepatic recurrence (P =
      0.028 and P = 0.030). High serum AFP combined with high telomerase activity in
      liver without tumor had a significant ability to predict poor survival (OR:
      11.19, CI: 1.95-64.12, P = 0.007). CONCLUSION: Tumor telomerase is an independent
      predictor of recurrence. Simultaneous high remnant liver telomerase and high
      serum AFP is a strong negative predictor of survival.

PMID- 17429566
TI  - Extended resection for thyroid disease has less operative morbidity than limited
      resection.
AB  - BACKGROUND: Theodor Kocher, surgeon and Nobel laureate, has influenced thyroid
      surgery all over the world: his treatment for multinodular goiter-subtotal
      thyroidectomy-has been the "Gold Standard" for more than a century. However,
      based on a new understanding of molecular growth mechanisms in goitrogenesis, we
      set out to evaluate if a more extended resection yields better results. METHODS:
      Four thousand three hundred and ninety-four thyroid gland operations with 5,785
      "nerves at risk" were prospectively analyzed between 1972 and 2002. From 1972 to
      1990, the limited Kocher resections were performed, and from 1991 to 2002 a more
      radical resection involving at least a hemithyroidectomy was performed. RESULTS:
      The incidence of postoperative nerve palsy was 3.6%; in the first study period
      and 0.9%; in the second (P < 0.001, Fisher's exact). Postoperative
      hypoparathyroidism decreased from 3.2%; in the first period to 0.64%; in the
      second (P < 0.01). The rate of reoperation for recurrent disease was 11.1%; from
      1972 to 1990 and 8.5%; from 1991 to 2002 (P < 0.01). CONCLUSIONS: Extended
      resection for multinodular goiter not only significantly reduced morbidity, but
      also decreased the incidence of operations for recurrent disease. Our findings in
      a large cohort corroborate the suggestions that Kocher's approach should be
      replaced by a more radical resection, which actually was his original intention
      more than 130 years ago.

PMID- 17429567
TI  - Management of solid-pseudopapillary neoplasms of the pancreas: a comparison with
      standard pancreatic neoplasms.
AB  - BACKGROUND: Solid-pseudopapillary neoplasms (SPNs) of the pancreas are
      increasingly diagnosed, but the exact surgical management in terms of extent of
      the resection is not well defined. MATERIALS AND METHODS: Patients operated on in
      our hospital between January 1993 and March 2005 formed the study groups.
      RESULTS: From 659 consecutive resections for pancreatic neoplasms, 12 female
      patients (1.8%) with a median age of 21 years who underwent resection for (SPN)
      are compared with the remaining 647 pancreatic resection patients. Jaundice (SPN
      0 versus PR 73%, p < 0.001) and weight loss (SPN 0 versus PR 49%, p = 0.001)
      occurred significantly less often. Neoplasms were distributed equally among the
      pancreatic head (SPN 5 out of 12 patients versus PR 88%, p < 0.001) and
      corpus/tail (SPN 6 out of 12 patients versus PR 8%, p < 0.001). The operative
      time was significantly shorter (SPN 233 min versus PR 280 min, p = 0.012), and
      there were significantly fewer complications (SPN 1 of 12 patients versus PR 48%,
      p = 0.007). The mortality was not different (SPN 0 versus PR 1.6%, p = 1.000),
      and the hospital stay was significantly shorter (SPN 9 days versus PR 15 days, p
      = 0.012). The median size of the neoplasms was significantly larger (SPN 6.9 cm
      versus PR 2.5 cm). The median number of lymph nodes harvested was significantly
      fewer (SPN 1 versus PR 6, p = 0.001), and lymph node metastases occurred
      significantly less often (SPN 0 versus PR 64%, p < 0.001). The 5-year survival of
      SPN patients was 100% and is significantly better compared with survival of
      patients with pancreatic adenocarcinoma (12%, p < 0.001) and ampulla of Vater
      adenocarcinoma (22%, p = 0.005). CONCLUSIONS: Patients with solid-pseudopapillary
      neoplasms of the pancreas present differently and the course of the disease is
      more benign. These patients can be adequately managed by pylorus-preserving
      pancreatoduodenectomy or spleen-preserving distal pancreatectomy with excellent
      early and long-term results.

PMID- 17429568
TI  - 7201 carcinoids: increasing incidence overall and disproportionate mortality in
      the elderly.
AB  - INTRODUCTION: The aim of the study was to determine outcomes for respiratory and
      gastrointestinal carcinoid tumors utilizing a large cancer registry. METHODS:
      Cases of respiratory and gastrointestinal carcinoid from the Florida Cancer Data
      System (FCDS) from 1981 to 2001 were reviewed. Descriptive statistics, age
      adjusted tumor incidence, and survival rates were determined. RESULTS: A total of
      7201 cases of malignant carcinoid were identified. Pulmonary and gastrointestinal
      carcinoid tumors comprised 82% of all carcinoids encountered. The mean age was
      64.4 +/- 0.15 years. Stratified by location, there were 3000 (51.4%) foregut
      carcinoids (including those found in the respiratory tree-2325 in the lung), 2130
      (36.5%) midgut carcinoids, and 712 (12.2%) hindgut carcinoids. Second, distinct
      malignancies were observed in 23% of cases. The total age-adjusted incidence rate
      has increased from 0.62 per 100,000 in 1980 to 5.17 per 100,000 in 2000. Overall
      median survival was 21.97 months. The median survival was 19.0 months for foregut
      carcinoids (excluding those arising in the respiratory tract); 33.9 months for
      midgut tumors; and 22.7 months for hindgut carcinoids. There was a statistically
      significant better survival for those with midgut tumors than for those in the
      other groups (P < 0.001). Age < 60 years, white race, and female sex were all
      associated with better survival (P < 0.01). CONCLUSIONS: The incidence of
      pulmonary and gastrointestinal carcinoids has dramatically increased since 1981.
      Tumor location and age > or = 60 years are the strongest predictors of mortality.

PMID- 17429569
TI  - CT angiographic depiction of a supraclinoid ICA fenestration mimicking aneurysm,
      confirmed with catheter angiography.
AB  - Fenestrations (segmental duplications) of the intracranial arteries are rare
      anomalies that have been associated with aneurysms. Fenestrations of the
      supraclinoid ICA are extremely rare, with only a few reported cases. We present a
      supraclinoid ICA fenestration, which on axial CTA images initially mimicked an
      aneurysm, but was correctly delineated as a fenestration on multiplanar
      reformatted and 3D reconstructed images. Confirmation was made with conventional
      angiography. To our knowledge, this represents the first time that this rare
      variant has been identified with cross-sectional imaging. A review of the
      literature including proposed embryology is provided.

PMID- 17429570
TI  - Antiviral activity of oxidized polyamines.
AB  - Polyamines, oxidized by serum amine oxidase, yield aminoaldehydes and hydrogen
      peroxide. Acrolein may be formed from the aminoaldehydes by a spontaneous beta
      elimination process. These oxidation products "oxidized polyamines" inhibit
      bacterial growth and exhibit anticancer activity. The antimicrobial activity of
      oxidized polyamines is not limited to bacteria; and the inactivation of bacterial
      viruses, plant viruses and animal viruses, was also reported. Bacteriophages of
      the T-odd series are permeable and were inactivated by oxidized polyamines. The
      inactive phages absorb to their bacterial host and injected their DNA, which
      formed a stable inactive complex with the aminoaldehydes. Aminoaldehydes,
      synthesized chemically, also inactivated viruses. The growth of the plant
      viruses: Tobacco mosaic virus, Potato virus X and Alfalfa mosaic virus was also
      inhibited by oxidized polyamines. The animal viruses, which were inactivated by
      oxidized polyamines included Myxoviruses (influenza and Newcastle disease
      viruses), West Nile, vaccinia and Sindbis viruses. These findings may have
      practical implications.

PMID- 17429571
TI  - Unique polyamines produced by an extreme thermophile, Thermus thermophilus.
AB  - Recent research progress on polyamines in extreme thermophiles is reviewed.
      Extreme thermophiles produce two types of unique polyamines; one is longer
      polyamines such as caldopentamine and caldohexamine, and the other is branched
      polyamines such as tetrakis(3-aminopropyl)ammonium. The protein synthesis
      catalyzed by a cell-free extract of Thermus thermophilus, an extreme thermophile,
      required the presence of a polyamine and the highest activity was found in the
      presence of tetrakis(3-aminopropyl)ammonium. In vitro experiments, longer
      polyamines efficiently stabilized double stranded nucleic acids and a branched
      polyamine, tetrakis(3-aminropyl)ammonium, stabilized stem-and-loop structures. In
      T. thermophilus, polyamines are synthesized from arginine by a new metabolic
      pathway; arginine is converted to agmatine and then agmatine is aminopropylated
      to N(1)-aminopropylagmatine which is converted to spermidine by an enzyme coded
      by a gene homologous to speB (a gene for agmatinase). In this new pathway
      spermidine is not synthesized from putrescine. Reverse genetic studies indicated
      that the unique polyamines are synthesized from spermidine.

PMID- 17429572
TI  - Intragenomic diversity of the V1 regions of 16S rRNA genes in high-alkaline
      protease-producing Bacillus clausii spp.
AB  - Alkaliphilic Bacillus sp. strain KSM-K16, which produces high-alkaline M
      protease, was characterized phenotypically, biochemically and genetically. This
      strain was identified as Bacillus clausii based on the results of taxonomic
      studies, including sequencing of the 16S rRNA gene and DNA-DNA hybridization.
      Seven rRNA operons in the genome were identified by pulsed-field gel
      electrophoresis. Sequencing of cloned 16S rRNA genes revealed two distinct types
      of variable region V1. Moreover, some cloned 16S rRNA genes in some of the
      reference strains of B. clausii had a V1 region of yet another type. The B.
      clausii strains could clearly be divided into at least two subgroups based on the
      frequencies of the types of cloned V1 sequence. Bacillus sp. strain KSM-K16 was
      found to be in a different phylogenetic position from other high-alkaline
      protease-producing strains of B. clausii.

PMID- 17429573
TI  - Structure-dependent relationships between growth temperature of prokaryotes and
      the amino acid frequency in their proteins.
AB  - We studied the amino acid frequency and substitution patterns between homologues
      of prokaryotic species adapted to temperatures in the range 0-102 degrees C, and
      found a significant temperature-dependent difference in frequency for many of the
      amino acids. This was particularly clear when we analysed the surface and core
      residues separately. The difference between the surface and the core is getting
      more pronounced in proteins adapted to warmer environments, with a more
      hydrophobic core, and more charged and long-chained amino acids on the surface of
      the proteins. We also see that mesophiles have a more similar amino acid
      composition to psychrophiles than to thermophiles, and that archea appears to
      have a slightly different pattern of substitutions than bacteria.

PMID- 17429574
TI  - Stress responses and metal tolerance of Chlamydomonas acidophila in metal
      enriched lake water and artificial medium.
AB  - Chlamydomonas acidophila faces high heavy-metal concentrations in acidic mining
      lakes, where it is a dominant phytoplankton species. To investigate the
      importance of metals to C. acidophila in these lakes, we examined the response of
      growth, photosynthesis, cell structure, heat-shock protein (Hsp) accumulation,
      and metal adsorption after incubation in metal-rich lake water and artificial
      growth medium enriched with metals (Fe, Zn). Incubation in both metal-rich lake
      water and medium caused large decreases in photosystem II function (though no
      differences among lakes), but no decrease in growth rate (except for medium +
      Fe). Concentrations of small Hsps were higher in algae incubated in metal-rich
      lake-water than in metal-enriched medium, whereas Hsp60 and Hsp70A were either
      less or equally expressed. Cellular Zn and Fe contents were lower, and metals
      adsorbed to the cell surface were higher, in lake-water-incubated algae than in
      medium-grown cells. The results indicate that high Zn or Fe levels are likely not
      the main or only contributor to the low primary production in mining lakes, and
      multiple adaptations of C. acidophila (e.g., high Hsp levels, decreased metal
      accumulation) increase its tolerance to metals and permit survival under such
      adverse environmental conditions. Supposedly, the main stress factor present in
      the lake water is an interaction between low P and high Fe concentrations.

PMID- 17429575
TI  - Variation in diet and ranging of black and white colobus monkeys in Kibale
      National Park, Uganda.
AB  - Recently, considerable intraspecific variation in the diets and ranging behavior
      of colobine monkeys has been described, although in most cases this has involved
      documenting variation between, not within, sites. Some African colobines, such as
      guerezas (Colobus guereza), are relatively abundant in disturbed habitats that
      are very heterogeneous, raising the intriguing possibility that even groups with
      overlapping home ranges may exhibit large behavioral differences. If such
      differences occur, it will be important to understand what temporal and spatial
      scales adequately portray a species' or population's diet and ranging behavior.
      This study documents within-site variation in the diet and ranging behavior of
      guerezas in the habitat types in which they are described to be most successful
      forest edge and regenerating forest. We collected data on eight groups of
      guerezas with overlapping home ranges for 3-5 months each in Kibale National
      Park, Uganda. The guerezas were highly folivorous, with leaves constituting 78.5
      94.0% of the groups' diets. The percentage of mature leaves and fruit in the diet
      varied widely among and within groups. We show that differences among groups in
      the intensity with which they fed on specific tree species were not just related
      to phenology, but also to differences in the forest compositions of groups' core
      areas. Range size estimates varied more than fivefold among groups and the
      minimum distance from groups' core areas to eucalyptus forest (which all groups
      regularly fed in) was a better predictor of range size than was group size. These
      results reveal considerable variation in the diet and ranging behavior among
      groups with overlapping ranges and have implications for comparative studies,
      investigations of within- and between-group feeding competition, and the
      potential for populations to adapt to anthropogenic or natural environmental
      change.

PMID- 17429577
TI  - Primary conjunctival epithelial cyst of the orbit.
AB  - BACKGROUND: A primary conjunctival epithelial cyst is an uncommon lesion that
      consists of nonkeratized, stratified squamous epithelium without dermal
      appendages. METHODS: Case report. RESULTS: A 57-year-old woman presented with a
      soft mass in the anterior portion of the nasal orbit. Magnetic resonance imaging
      demonstrated a rounded, cystic lesion between the right eye and the nasal bone.
      Histopathological examination following complete surgical excision disclosed a
      conjunctival epithelial cyst lined by nonkeratinized cuboidal epithelium without
      goblet cells and adnexal structures. CONCLUSION: A conjunctival epithelial cyst
      should be considered in the differential diagnosis of a mass in the anterior
      portion of nasal or superonasal orbit.

PMID- 17429576
TI  - Quantitative PCR analysis of the expression profile of genes related to multiple
      drug resistance in tumors of the central nervous system.
AB  - OBJECTIVES: To evaluate and compare the profile of expression of genes related to
      drug resistance in brain tumors and to analyze the impact of the increased
      expression of these genes on overall survival. METHODS: Eighty microdissected
      brain tumor samples from 79 patients were analyzed by RQ-PCR for the genes MDR1,
      MRP1, MRP3, LRP and BCRP. Protein expression was assessed by immunohistochemistry
      for MRP1 and LRP genes. Pediatric cases (0 to 20 years): 46 (17F:29M, median age
      7.3 +/- 5.9 years); adult tumors: 33 (17F:16M, median age 46.6 +/- 14.5 years).
      Histological diagnoses: 21 astrocytomas I and II, 28 astrocytomas III and
      glioblastomas, 17 medulloblastomas, 8 ependymomas, and 6 oligodendrogliomas.
      RESULTS: glial tumors expressed higher MDR1 (P = 0.003) and BCRP (P = 0.03)
      levels than embryonic tumors. Low-grade astrocytomas expressed high MDR1 (P =
      0.001), MRP3 (P = 0.01) and LRP (P = 0.02) levels. The MRP1 gene was
      preferentially expressed by medulloblastomas (P = 0.04) and ependymomas (P =
      0.04); ependymomas also presented an increase of LRP (P = 0.02). The mRNA levels
      of MRP1 and LRP genes were associated to protein expression. The profile of gene
      expression of primary pilocytic astrocytomas of the hypothalamus and of the other
      locations was similar. Increased expression of resistance genes, separately or
      jointly, was not correlated with shorter overall survival in patients with
      medulloblastomas/PNET and malignant gliomas. CONCLUSIONS: Drug resistance genes
      do not explain the higher sensitivity of gliomas of the
      hypothalamus/pituitary/optic pathways to chemotherapy. The increased expression
      of resistance genes had no impact on the overall survival of patients with
      medulloblastomas/PNET and high grade gliomas. High MDR1, MRP3 and LRP levels may
      be implicated in the primary resistance of pilocytic astrocytomas to
      chemotherapy.

PMID- 17429578
TI  - Three species of Caligus Muller, 1785 (Copepoda: Caligidae) parasitic on Caranx
      spp. (Teleostei: Carangidae) off Taiwan.
AB  - Three species of sea-lice (Siphonostomatoida: Caligidae) parasitic on marine
      fishes of the genus Caranx off Taiwan are reported. They are: Caligus fortis
      Kabata, 1965 on Caranx ignobilis (Forsskal); Caligus robustus Bassett-Smith, 1898
      on Caranx sexfasciatus Quoy & Gaimard; and Caligus inanis n. sp. on Caranx
      ignobilis. Caligus robustus is a widely distributed species, but this is the
      first report of C. fortis outside the Australian and Indian regions. The new
      species is distinguished from its congeners in lacking postantennal process and
      carrying a pair of tiny, tooth-like, sharp protuberances on the posterior margin
      of the cephalothoracic shield.

PMID- 17429579
TI  - Antimicrobial agents targeting the ribosome: the issue of selectivity and
      toxicity - lessons to be learned.

PMID- 17429580
TI  - The role of transmembrane domains in membrane fusion.
AB  - Biological membrane fusion is driven by different types of molecular fusion
      machines. Most of these proteins are membrane-anchored by single transmembrane
      domains. SNARE proteins are essential for intracellular membrane fusion along the
      secretory and endocytic pathway, while various viral fusogens mediate infection
      of eukaryotic cells by enveloped viruses. Although both types of fusion proteins
      are evolutionarily quite distant from each other, they do share a number of
      structural and functional features. Their transmembrane domains are now known to
      be critical for the fusion reaction. We discuss at which stages they might
      contribute to bilayer mixing.

PMID- 17429581
TI  - Cellular and molecular pathogenesis of type 1A diabetes.
AB  - Type 1A diabetes is an organ-specific autoimmune disease resulting from
      destruction of insulin-producing pancreatic beta-cells. The main susceptibility
      genes code for polymorphic HLA molecules and in particular alleles of class II
      MHC genes (DR, DQ and DP). Polymorphisms of individual genes outside the MHC also
      contribute to diabetes risk but recent evidence suggests that there are
      additional non-HLA genes determining susceptibility linked to the MHC. It is now
      possible using genetic and autoantibody assays to predict the development of type
      1A diabetes in the majority of individuals, and trials of diabetes prevention are
      underway.

PMID- 17429582
TI  - Structure, mechanism and catalytic duality of thiamine-dependent enzymes.
AB  - Thiamine is an essential cofactor that is required for processes of general
      metabolism amongst all organisms, and it is likely to have played a role in the
      earliest stages of the evolution of life. Here, we review from a structural
      perspective the enzymatic mechanisms that involve this cofactor. We explore
      asymmetry within homodimeric thiamine diphosphate (ThDP)-dependent enzyme
      structures and discuss how this may be correlated with the kinetic properties of
      half-of-the-sites reactivity, and negative cooperativity. It is likely these
      structural and kinetic hallmarks may arise through reciprocal coupling of active
      sites. This mode of communication between distant active sites is not unique to
      ThDP-dependent enzymes, but is widespread in other classes of oligomeric enzyme.
      Thus, it appears likely to be a general phenomenon reflecting a powerful
      mechanism of accelerating the rate of a chemical pathway. Finally, we speculate
      on the early evolutionary history of the cofactor and its ancient association
      with protein and RNA.

PMID- 17429583
TI  - [Atypical mycobacteriosis of the skin caused by Mycobacterium abscessus in an
      immunocompetent woman].
AB  - Mycobacterium abscessus is the most pathogenic of the fast-growing mycobacteria,
      and it is resistant to most of the antimicrobial and tuberculostatic drugs
      available. This non-tuberculous mycobacterium is significant in medicine because
      it can contaminate post-traumatic wounds and be a causative agent in chronic skin
      and soft tissue infection after surgical procedures.A 60-year-old immunocompetent
      woman was suffering from chronic ulcers and abscesses on the heels and malleoli
      of both feet. Histological examination revealed a granulomatous inflammation with
      detection of acid-fast rods, albeit without fibrinoid necrosis. The repeated
      detection of atypical mycobacteria, which were ultimately identified as
      Mycobacterium abscessus, allowed the diagnosis of an atypical mycobacteriosis of
      the skin. This was successfully treated first with clarithromycin and rifabutin
      and later with a combination of ethambutol, minocycline, clofazimine and
      azithromycin.

PMID- 17429584
TI  - [Photocarcinogenesis. Molecular mechanisms and preventive strategies].
AB  - Ultraviolet (UV) radiation is the main carcinogen in the development of
      epithelial skin cancer. A variety of biological and molecular effects in the skin
      have been described. In order to avoid malignant transformation, various
      protective mechanisms have developed in the skin, whereby p53 plays a central
      role. UV signature mutations in p53, Ras and INK4a/ARF as well as UV-induced
      NFkappaB and cyclooxygenase 2 are principally involved in photocarcinogenesis.
      Chemoprevention has gained increasing importance for primary prevention. Numerous
      natural or synthetic substances can be antiinflammatory, antioxidative,
      proapoptotic or antiproliferative and suppress photocarcinogenesis. Extensive
      clinical data exist for the use of retinoids systemically or DNA repair enzymes
      topically. However, clinical trials are lacking, for example for green tea, which
      has been shown repeatedly to be chemoprotective in vitro and in mouse models
      after topical or oral application.

PMID- 17429585
TI  - [Topical therapy of squamous cell carcinoma].
AB  - Many forms of topical chemo- and immunotherapy are employed to treat skin
      cancers. Topical treatment is particularly attractive for field cancerization
      involving multiple non-melanoma skin cancers. The dermatologist must identify
      such patients and lesions and provide the most suited therapy.

PMID- 17429586
TI  - [Skin and mucosal ulcerations in heparin-induced thrombocytopenia (HIT) II].
AB  - About 0.1-2% of patients receiving heparin develop heparin-induced
      thrombocytopenia type II (HIT II) which is caused by antibodies directed against
      heparin-platelet factor 4 (PF4) complexes. Activation of thrombocytes and
      endothelial cells can lead to thrombocytopenia, venous and arterial thrombosis or
      thromboembolic events 10-14 days after the first dose. HIT II has a high
      mortality rate because of pulmonary emboli, cerebrovascular accidents, myocardial
      and limb infarctions. A 55-year-old patient with HIT II presented with arterial
      and venous thromboses and a silent myocardial infarction. In addition, he showed
      extensive skin and mucosal necrosis, an uncommon complication. Rheologic therapy
      with danaparoid Natrium, alprostadil alfadex and acetylsalicylic acid in
      combination with percutaneous transluminal angioplasties as well as local and
      systemic antiinflammatory therapy prevented further progression of the disease.

PMID- 17429587
TI  - [Successful therapy of ulcerated necrobiosis lipoidica non diabeticorum with
      cyclosporine A].
AB  - Necrobiosis lipoidica is an inflammatory granulomatous skin disease of unknown
      etiology which is associated with diabetes mellitus in about 60% of the patients.
      In 15-35% of the affected patients painful ulcerations may occur after minimal
      trauma which can be extremely refractory to therapy. Because of the unknown
      pathomechanisms, current therapeutic options are limited. We report on a 68-year
      old patient with an 18 year history of ulcerated necrobiosis lipoidica non
      diabeticorum of both lower limbs, which responded to systemic cyclosporine A.
      Based on this case, we discuss the role of cyclosporine A in patients with
      necrobiosis lipoidica in the context of the disease etiology.

PMID- 17429589
TI  - [New aspects of the pathophysiology of pneumonia].
AB  - Pneumonia can lead to the critical impairment of gas exchange in the lung. Due to
      the great variability of pneumonia causing pathogens, a large variety of diverse
      virulence factors act on the lung. Besides stimulation of unspecific defense
      mechanisms, activation of receptor-dependent cell-mediated innate immune defense
      mechanisms are critical for the pulmonary immune defense. Pathogen-associated
      molecules are detected via transmembraneous and cytosolic receptors of the host.
      This interaction stimulates the expression of immunomodulatory molecules via
      signal cascades. Of particular importance, in addition to direct pathogen-caused
      lung damage, is the overwhelming activation of the inflammatory response which
      can result in lung barrier failure and impairment of pulmonary gas exchange. In
      addition to the design of new antibiotics, innovative therapeutic strategies
      should therefore concentrate on the enhancement of antimicrobial mechanisms by
      concurrent limitation of inflammation.

PMID- 17429590
TI  - IGF-I assays: current assay methodologies and their limitations.
AB  - The diagnosis of disorders of growth hormone (GH) is dependent upon accurate
      measurement of insulin-like growth factor-I (IGF-I) concentrations since serum
      IGF-I assays have been found to be useful as a screening tests for the presence
      of growth hormone deficiency (GHD) in children and in both children and adults
      they have been found very useful in establishing the diagnosis of acromegaly. IGF
      I is also used extensively to monitor the response to GH treatment in children
      and adults and to monitor the response to treatment in acromegaly. Since IGF-I is
      influenced by several other hormones and physiologic factors as well as GH, a
      knowledge of its regulation is essential to understanding how to properly
      interpret the measurements. Several technical criteria are required for
      successful laboratory estimation of IGF-I values. These include elimination of
      interference of IGF-I-binding proteins (IGFBP), utilization of adequate numbers
      of normal subjects to define the normal ranges and importantly the use of high
      affinity, high specificity antisera that allow precise and reproducible
      measurements of the biologically active peptide. Cross comparisons of various
      commercial assays show that the results generally are similar when values are in
      the normal range. However, the assays have different performance characteristics
      when concentrations are either above or below the normal range. To obtain cross
      laboratory standardization for values outside the normal range requires
      utilization of similar, high-quality reagents and techniques that are reasonably
      comparable. Without this degree of standardization, cross comparisons among
      various reference laboratories are likely to continue to show wide divergence for
      values that are above or below the 95% confidence interval. A future goal should
      be the development of standard procedures and reagents that eliminate this degree
      of variability.

PMID- 17429591
TI  - Growth hormone levels in the diagnosis of growth hormone deficiency in adulthood.
AB  - Current guidelines for the diagnosis of adult growth hormone deficiency (GHD)
      state that the diagnosis must be proven biochemically by provocative testing that
      is done within the appropriate clinical context. The need for reliance on
      provocative testing is based on evidence that the evaluation of spontaneous
      growth hormone (GH) secretion over 24 h and the measurement of IGF-I and IGFBP-3
      levels do not distinguish between normal and GHD subjects. Regarding IGF-I, it
      has been demonstrated that very low levels in patients highly suspected for GHD
      (i.e., patients with childhood-onset, severe GHD, or with multiple
      hypopituitarism acquired in adulthood) may be considered definitive evidence for
      severe GHD obviating the need for provocative tests. However, normal IGF-I levels
      do not rule out severe GHD and therefore adults suspected for GHD and with normal
      IGF-I levels must undergo a provocative test of GH secretion. The insulin
      tolerance test (ITT) is the test of choice, with severe GHD being defined by a GH
      peak less than 3 microg/l, the cut-off that distinguishes normal from GHD adults.
      The ITT is contraindicated in the presence of ischemic heart disease, seizure
      disorders, and in the elderly. Other tests are as reliable as the ITT, provided
      they are used with appropriate cut-off limits. Glucagon stimulation, a classical
      test, and especially new maximal tests such as GHRH in combination with arginine
      or GHS (i.e., GHRP-6) have well-defined cut-off limits, are reproducible, are
      independent of age and gender, and are able to distinguish between normal and GHD
      subjects. The confounding effect of overweight or obesity on the interpretation
      of the GH response to provocative tests needs to be considered as the
      somatotropic response to all stimuli is negatively correlated with body mass
      index. Appropriate cut-offs for lean, overweight, and obese subjects must be used
      in order to avoid false-positive diagnoses of severe GHD in obese adults.

PMID- 17429592
TI  - Growth hormone assays: current methodologies and their limitations.
AB  - Measurement of circulating growth hormone (GH) concentrations is essential in
      diagnosis of either GH deficiency or GH excess. The invention of immunoassays for
      the measurement of peptide hormones was a major breakthrough, enabling the
      routine analysis of GH concentrations in larger series of samples. Over the last
      few decades, measurement technology has evolved from less sensitive, mainly
      radioactive assays based on polyclonal antisera to the latest generations of
      highly sensitive chemiluminescence methods employing monoclonal antibodies.
      Unfortunately, the development of newer assays did not lead to better agreement
      among the results obtained by different assay methods. On the contrary, the
      differences tended to increase when monoclonal antibody based assays became more
      popular. The actual value reported for the GH concentration in a specific
      patient's sample still mainly depends on the method used by the respective
      laboratory, limiting the applicability of international consensus guidelines in
      clinical practice. The heterogeneity of the analyte itself, the availability of
      different reference preparations for calibration and the interference from matrix
      components such as GH binding protein are among the reasons why standardizing GH
      assays is difficult. An additional challenge arose from the availability of a GH
      receptor antagonist for the treatment of acromegaly, which is basically a mutated
      form of GH and therefore interferes in many GH assays. This review provides an
      overview on GH assays used in clinical practice, their limitations and the
      potential next steps towards standardization.

PMID- 17429593
TI  - IGF-I measurements in the diagnosis of adult growth hormone deficiency.
AB  - Although serum insulin-like growth factor I (IGF-I) concentrations have utility
      as a screening test for growth hormone (GH) deficiency in children and young
      adults, they are less accurate for screening in adults over 40 years of age.
      There are two main limitations in the clinical use of IGF-I levels as a marker of
      GH secretion. First, IGF-I synthesis is not only regulated by GH but also by
      nutrient supply and by other hormones; second, low IGF-I levels in the presence
      of normal or increased GH secretion may reflect a peripheral resistance to GH
      action. Although serum IGF-I cannot be used as a stand-alone test for the
      diagnosis of adult GH deficiency, very low IGF-I levels in the context of
      documented hypothalamic or pituitary disease may be helpful in identifying
      patients with a high probability of GH deficiency. In the presence of two or more
      additional pituitary hormone deficiencies, an IGF-I level <84 microg/l (assayed
      by Esoterix Endocrinology, Inc. Calabasas Hills, CA, USA) indicates a 99%
      probability of GH deficiency. As this cut-off value has not been validated for
      other IGF-I assays, an IGF-I standard deviation score (SDS) of <-3 may be
      considered in adults over age 28; an even lower IGF-I SDS is needed for diagnosis
      in younger adults. In clinical practice, other causes of low serum IGF-I such as
      malnutrition, diabetes, hypothyroidism, liver disease, etc., should be excluded
      before applying these diagnostic criteria.

PMID- 17429594
TI  - Approach to the evaluation of the GH/IGF-axis in patients with pituitary disease:
      which test to order.
AB  - The diagnosis of adult growth hormone deficiency (AGHD) and acromegaly involves
      assessment of serum growth hormone (GH) and insulin-like growth factor-1 (IGF-1)
      concentrations. The diagnosis of AGHD typically requires a provocative test of GH
      reserve, but is supported by demonstration of low-serum IGF-1 levels. Therapeutic
      monitoring of rhGH replacement is performed utilizing measurement of serum IGF-1
      concentrations. In patients with suspected acromegaly, the diagnosis is confirmed
      by elevated serum IGF-1 levels and further validated by the presence of elevated
      GH levels both before and following an oral glucose load. A goal of acromegaly
      therapy is to normalize IGF-1 concentrations, and, depending on the therapeutic
      modality, GH levels as well. Using case based clinical scenarios, we have
      presented a standard approach to the biochemical diagnosis and therapeutic
      monitoring of these disorders.

PMID- 17429595
TI  - Utility of free IGF-I measurements.
AB  - For nearly 30 years, the endogenous bioactivity of insulin-like growth factor I
      (IGF-I) has been estimated by its circulating concentrations of immunoreactive
      IGF-I, obtained after either removal or inactivation of the IGF-binding proteins
      (IGFBPs), and today serum/plasma total IGF-I serves as a useful parameter in the
      diagnosis and clinical control of growth hormone (GH) disorders. Different assays
      for the measurement of free, unbound IGF-I were introduced more than a decade
      ago. Nevertheless, this measurement remains controversial, and in daily clinical
      practice serum total IGF-I has retained its position as the most widely used IGF
      related measurement in GH disorders. This review will provide a survey of data on
      free versus total IGF-I, with particular reference to GH disorders. As it will be
      clear, there is reasonable clinical evidence to conclude that both in the
      diagnosis of as well as during treatment of patients with GH disorders,
      serum/plasma total IGF-I should remain the primary IGF-related measurement.
      However, in certain patients the inclusion of free IGF-I may be useful and
      therefore, some guidelines for the inclusion of free IGF-I measurements will be
      given.

PMID- 17429596
TI  - Not so simple: the complexity of phosphotyrosine signaling at cadherin adhesive
      contacts.
AB  - Cadherin cell-cell adhesion critically determines tissue organization and
      integrity in many organs of the body. Cadherin function influences patterning and
      morphogenesis while cadherin dysfunction contributes to disease, notably tumor
      invasion and metastasis. Cell signaling events are intimately linked with
      cadherin function; it is increasingly apparent that not only do cellular signals
      regulate cadherin function, but cadherins can also, in turn, modulate cell
      signaling itself. In this review, we discuss the complex interrelationship
      between phosphotyrosine-based cell signaling and cadherin adhesion. We focus on
      the interplay of events that occur at the cell surface and address three issues:
      the diverse mechanisms that activate phosphotyrosine signaling at cadherin cell
      cell contacts, the functional impact of such signaling for cadherin adhesion, and
      the emerging capacity for cadherins to regulate growth factor signaling.

PMID- 17429597
TI  - The ubiquitin- and proteasome-dependent degradation of COX-2 is regulated by the
      COP9 signalosome and differentially influenced by coxibs.
AB  - The cyclooxygenase-2 (COX-2) enzyme is induced upon inflammation and in
      neoplastic tissues. It produces prostaglandins that stimulate tumor angiogenesis
      and tumor growth. Therefore, destruction and/or specific inhibition of COX-2
      should be an important aspect of future tumor therapy. Recently, clinical
      application of specific COX-2 inhibitors called coxibs became doubtfully because
      they produce serious renal and cardiovascular complications under long term
      application. The exact underlying mechanisms are poorly understood and the
      different effects of diverse coxibs are not explained. It has been demonstrated
      before that COX-2 is degraded by the ubiquitin (Ub) proteasome system (UPS).
      However, how ubiquitination is accomplished and regulated was unclear. An
      important regulator of the UPS is the COP9 signalosome (CSN), which controls the
      stability of many proteins. Here we show that the proteasome-dependent
      degradation of COX-2 in HeLa cell lysate and in HeLa cells was stimulated by
      curcumin, an inhibitor of CSN-associated kinases. These data suggest a function
      of the CSN in the degradation of COX-2. In addition, proteolysis of COX-2 was
      significantly accelerated by parecoxib, but not by celecoxib or rofecoxib. By
      density gradient centrifugation and immunoprecipitation we demonstrate that COX-2
      physically interacts with the CSN. Moreover, COX-2 is associated with large
      complexes consisting of the CSN, cullin-RING Ub ligases and the 26S proteasome.
      Pulldown experiments with Flag-COX-2 revealed cullin 1 and cullin 4 as components
      of the large super-complexes. Cullin 1 and 4 are scaffolding proteins of Ub
      ligases that presumably ubiquitinate COX-2. Treatment of HeLa cells with
      parecoxib results in an accelerated degradation of endogenous COX-2 accompanied
      by an increase of COX-2-Ub conjugates. In HeLa cells parecoxib is converted to
      the selective COX-2 inhibitor valdecoxib. Addition of valdecoxib also stimulates
      COX-2 degradation in HeLa cells. We therefore conclude that valdecoxib
      specifically interacts with COX-2 and induces a conformation accessible for
      ubiquitination and degradation.

PMID- 17429598
TI  - Transcriptional regulation of neurogenesis: potential mechanisms in cerebral
      ischemia.
AB  - Recent data provides evidence that new neurons are born in cerebral ischemia.
      Although ultimate evidence for their functional importance is lacking,
      correlational data suggest that they contribute to recovery. Therefore, the
      underlying mechanisms of neurogenesis are interesting as a basis for
      pharmacological enhancement of the phenomenon. Neurogenesis is a multistep
      process that includes proliferation of precursor cells, migration of the newborn
      cells to the site of lesion, differentiation, integration into neuronal circuits,
      and survival. All these steps rely on gene transcription. However, only
      preliminary data about the specific transcriptional control of neurogenesis in
      cerebral ischemia have been obtained so far. To promote this investigation, we
      review currently available information on six pathways (Notch, Wnt/beta-catenin,
      NF-kappaB, signal transducers and activators of transcription (STA) 3, HIF-1, and
      cyclic AMP response element-binding protein [CREB]) that have been shown to
      regulate transcription in neurogenesis and that have been implicated in cerebral
      ischemia. With the exception of CREB, direct involvement in postischemic
      neurogenesis is quite conjectural and much more must be learned to draw practical
      conclusions.

PMID- 17429600
TI  - Evidence for a male-produced pheromone in Tetropium fuscum (F.) and Tetropium
      cinnamopterum (Kirby) (Coleoptera: Cerambycidae).
AB  - (E)-6,10-dimethyl-5,9-undecadien-2-ol (geranyl acetol), termed here fuscol, was
      identified as a male-produced pheromone emitted by Tetropium fuscum (F.) and
      Tetropium cinnamopterum Kirby. In field experiments, traps baited with synthetic
      fuscol alone were not significantly attractive, but the combination of fuscol
      plus host volatiles (a synthetic blend of monoterpenes plus ethanol) attracted
      significantly more male and female T. fuscum and female T. cinnamopterum than did
      host volatiles alone. This is the first homoterpenoid alcohol to be described in
      the Cerambycidae, and the first pheromone reported from the sub-family
      Spondylidinae.

PMID- 17429599
TI  - Natriuretic peptide receptor B signaling in the cardiovascular system: protection
      from cardiac hypertrophy.
AB  - Natriuretic peptides (NP) represent a family of structurally homologous but
      genetically distinct peptide hormones involved in regulation of fluid and
      electrolyte balance, blood pressure, fat metabolism, cell proliferation, and long
      bone growth. Recent work suggests a role for natriuretic peptide receptor B (NPR
      B) signaling in regulation of cardiac growth by either a direct effect on
      cardiomyocytes or by modulation of other signaling pathways including the
      autonomic nervous system. The research links NPR-B for the first time to a
      cardiac phenotype in vivo and underlines the importance of the NP in the
      cardiovascular system. This manuscript will focus on the role of NPR-B and its
      ligand C-type natriuretic peptide in cardiovascular physiology and disease and
      will evaluate these new findings in the context of the known function of this
      receptor, with a perspective on how future research might further elucidate NPR-B
      function.

PMID- 17429602
TI  - A QTL on chromosome 6A in bread wheat (Triticum aestivum) is associated with
      longer coleoptiles, greater seedling vigour and final plant height.
AB  - Wheat crops with greater early vigour shade the soil surface more rapidly and
      reduce water loss. Evaporative losses affect water-use efficiency particularly in
      drier regions where most of the rainfall occurs early in the growing season
      before canopy closure. Greater seedling leaf area and longer coleoptiles are
      major determinants of increased vigour and better crop establishment. A
      previously developed high vigour breeding line 'Vigour 18' was used to establish
      a large recombinant inbred family and framework map to identify a QTL on
      chromosome 6A that accounted for up to 8% of the variation for coleoptile length,
      14% of seedling leaf width and was associated with increased plant height. The
      SSR marker NW3106, nearest to the 6A QTL, was also associated with greater leaf
      width in a breeding population that was also derived from a cross involving the
      high vigour donor line 'Vigour18'. The association between the NW3106 marker and
      coleoptile length was validated in a second breeding population which was
      developed using an unrelated long coleoptile donor line. The 'Vigour18' allele of
      the QTL on chromosome 6A promoted coleoptile length and leaf width during early
      plant growth but was also associated with increased plant height at maturity.
      Markers linked to the QTL are being used to increase the frequency of increased
      vigour and long coleoptile alleles in early generations of breeding populations.

PMID- 17429601
TI  - [Tolerance to perioperative anemia. Mechanisms, influencing factors and limits].
AB  - The expected cost explosion in transfusion medicine increases the socio-economic
      significance of specific institutional transfusion programs. In this context the
      estimated use of the patient's physiologic tolerance represents an integral part
      of any blood conservation concept. The present article summarizes the mechanisms,
      influencing factors and limits of this natural tolerance to anemia and deduces
      the indication for perioperative red blood cell transfusion. The current
      recommendations coincide to the effect that perioperative transfusion is
      unnecessary up to a Hb concentration of 10 g/dl (6.21 mmol/l) even in older
      patients with cardiopulmonary comorbidity and is only recommended in cases of Hb
      <6 g/dl (<3.72 mmol/l) in otherwise healthy subjects including pregnant women and
      children. Critically ill patients with multiple trauma and sepsis do not seem to
      benefit from transfusions up to Hb concentrations >9 g/dl (>5.59 mmol/l). In
      cases of massive hemorrhaging and diffuse bleeding disorders the maintenance of a
      Hb concentration of 10 g/dl (6.21 mmol/l) seems to contribute to stabilization of
      coagulation.

PMID- 17429603
TI  - TCF7L2 in the Go-DARTS study: evidence for a gene dose effect on both diabetes
      susceptibility and control of glucose levels.
AB  - AIMS/HYPOTHESIS: The gene encoding transcription factor 7-like 2 (TCF7L2) has
      been identified as a type 2 diabetes locus from genome-wide linkage studies and
      subsequent association analysis. We investigated the role of two common variants
      in TCF7L2 in a large case-control study recruited from the Tayside region of
      Scotland, UK. SUBJECTS AND METHODS: We genotyped 6,516 participants for
      rs12255372 and rs7903146 and analysed the role in type 2 diabetes susceptibility
      using binary logistic regression. Age, sex and obesity status were examined as
      covariates. The distribution of the genotypes within different treatment groups
      of cases was examined. RESULTS: Both variants were associated with type 2
      diabetes (p < 10(-13)). The variants were present at very similar frequencies and
      were in strong linkage disequilibrium (R(2) = 0.88, D' = 0.89). A gene dosage
      effect of the rare allele of both variants was observed, the heterozygote CT
      group of rs7903146 having an odds ratio of 1.36 (95% CI 1.2-1.5, p=1.54 x 10(-7))
      for type 2 diabetes and the TT homozygote having a greater risk (OR = 2.03, 95%
      CI 1.7-2.5, p=1.40 x 10(-12)). An interaction with sex was observed, the males
      displaying a higher degree of genotype-associated risk compared with the females
      (p = 0.023). The T allele was associated with increased HbA(1c) levels in both
      cases and controls, and with decreased BMI and waist circumference in case but
      not controls. The T allele was overrepresented in individuals requiring insulin
      treatment and underrepresented in the patients being managed by diet alone (p =
      0.006). CONCLUSIONS: We have confirmed TCF7L2 to be a diabetes locus in a large
      case-control study in Tayside, UK. Our data suggest that variants of TCF7L2 may
      be associated with increased disease severity and therapeutic failure.

PMID- 17429604
TI  - A diabetic life before and after the insulin era.

PMID- 17429605
TI  - Enhanced activity of the myocardial Na+/H+ exchanger contributes to left
      ventricular hypertrophy in the Goto-Kakizaki rat model of type 2 diabetes:
      critical role of Akt.
AB  - AIMS/HYPOTHESIS: Diabetes mellitus is a strong risk factor for the development of
      heart failure, and left ventricular (LV) hypertrophy has been detected in a
      significant proportion of diabetic patients. Because several studies have
      suggested that the Na(+)/H(+) exchanger (NHE1) plays a part in the molecular
      mechanisms involved in cardiac hypertrophy, we investigated its activity and its
      role in LV myocytes from the Goto-Kakizaki (GK) rat model of type 2 diabetes.
      MATERIALS AND METHODS: Fluorometric measurements were used to assess sarcolemmal
      NHE1 activity in isolated myocytes. NHE1 levels and the possible molecular
      pathways driving and/or related to NHE1 activity were investigated in relation to
      the diabetic LV phenotype. RESULTS: Enhanced NHE1 activity was associated with LV
      myocyte hypertrophy. This occurred in the absence of any change in NHE1 protein
      levels; however, activation of several molecular pathways related to NHE1
      activity was demonstrated. Thus, phosphorylation of the extracellular signal
      regulated protein kinase (Erk), of the protein kinase Akt (also known as protein
      kinase B) and of the Ca(2+)/calmodulin-dependent kinase II was increased in GK LV
      myocytes. Intracellular Ca(2+) levels were also increased. Chronic treatment (10
      12 weeks) with the NHE1 inhibitor cariporide normalised NHE1 activity, decreased
      [Formula: see text] levels and reduced LV myocyte hypertrophy. Moreover, among
      the various activated pathways, cariporide treatment markedly reduced Akt
      activity only. CONCLUSIONS/INTERPRETATION: These findings indicate that
      activation of the Akt pathway represents a likely mechanism mediating the
      hypertrophic effect of increased NHE1 activity in the GK model of type 2
      diabetes.

PMID- 17429606
TI  - Urinary biomarker of oxidative stress correlating with outcome in critically
      septic patients.
AB  - OBJECTIVE: To determine whether urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an
      in vivo parameter of oxidative stress, is correlated with the outcome of
      critically septic patients. DESIGN AND SETTING: Clinical outcome study in an
      adult medical intensive care unit (ICU). PATIENTS: 85 consecutive septic patients
      (59 men, 26 women). MEASUREMENTS AND RESULTS: Patient characteristics and the
      clinical course were examined. Urinary 8-OHdG was analyzed using isotope-dilution
      liquid chromatography with tandem mass spectrometry (LC/MS/MS). ICU mortality was
      25.9% (22/85) and hospital mortality 38.8% (33/85). Survivors' APACHEII scores on
      days 1 and 3 and the difference between them differed significantly from those of
      nonsurvivors (day 1, 21.0+/-7.1 vs. 25.9+/-8.0; day 3, 15.0+/-5.8 vs. 23.2+/-8.3;
      difference, 6.0+/-5.5 vs. 1.7+/-6.6). Urinary 8-OHdG was significantly lower in
      survivors than in nonsurvivors on day 1 (1.8+/-2.4 vs. 3.0+/-2.4). The area under
      receiver operating characteristic curve analysis for the association between day
      1 urinary 8-OHdG and ICU mortality was 0.71. The comparison performed upon
      discharge from hospital revealed similar results. CONCLUSIONS: This is a
      preliminary study. Excretion of urinary 8-OHdG, as measured using isotope
      dilution LC/MS/MS, and the APACHE II score were correlated with the outcome of
      critically septic patients in medical ICU.

PMID- 17429607
TI  - Effect of an immune-enhancing diet on lymphocyte in head-injured rats: what is
      the role of arginine?
AB  - OBJECTIVE: The benefit of immune-enhancing diets (IEDs) in the intensive care
      unit remains controversial. Considering their complexity, the role of each
      component, in particular arginine (Arg), in their properties is largely unknown.
      The aim of this study was to determine the role of arginine in the
      immunomodulatory effects of an IED (Crucial) in head-injured rats. DESIGN: Thirty
      four rats were randomized into five groups: AL (ad libitum), HI (head-injured),
      HI-STD (HI + standard enteral nutrition, EN), HI-STD-Arg (HI + standard EN + Arg
      in equimolar concentration to Arg in IED), and HI-IED (HI + IED). These
      isocaloric and isonitrogenous diets were administered over 4 days. After death,
      the thymus was removed and weighed. The density of CD25, CD4 and CD8 on
      lymphocytes from blood and from Peyer patches was evaluated. Mesenteric lymph
      nodes, liver and spleen were cultured for analysis of enterobacterial
      translocation and dissemination. MEASUREMENTS AND RESULTS: HI induced an atrophy
      of the thymus which was not corrected by the standard diet (HI 0.27 +/- 0.03, HI
      STD 0.35 +/- 0.03 vs. AL 0.49 +/- 0.02 g; p < 0.05). However, the standard diet
      supplemented with arginine limited the thymic atrophy and the IED restored thymus
      weight. CD25 density and interleukin-2 production were increased only in the HI
      STD-Arg and HI-IED groups (p < 0.05). Head injury induced enterobacterial
      translocation and dissemination which were blunted only in the HI-STD-Arg group
      (p < 0.05). CONCLUSIONS: In this rat HI model, arginine appears to be safe,
      contributes to a large extent to the immunomodulatory effects of the IED, and
      seems to limit enterobacterial translocation and dissemination more efficiently
      alone than in an IED.

PMID- 17429609
TI  - Tailored tibial tubercle transfer for patellofemoral malalignment: analysis of
      clinical outcomes.
AB  - The purpose of this study was to describe the surgical technique, and evaluate
      and analyze the clinical outcomes of patients who underwent tibial tubercle
      realignment in our institution. Reported results of tibial tubercle transfer for
      patellofemoral malalignment vary considerably. Most authors rely mainly on the
      passive intraoperative patellar tracking test in determining the new location of
      the tibial tubercle. Conversely, the senior author relocates the tibial tubercle
      based on the intraoperative active and passive patellar tracking tests and the
      condition of the patellar articular surface. The medical records of 66
      consecutive patients who underwent 80 tibial tubercle relocation procedures due
      to patellar instability or patellofemoral pain and maltracking were reviewed.
      Fifty-five patients with 69 operated knees participated in designated follow-ups
      which were conducted according to a predesigned protocol. The median follow-up
      was 6.2 years (range 2-13 years). Clinical outcomes significantly improved
      compared to the preoperative state; 72.5% of operated knees demonstrated good-to
      excellent results according to the Lysholm and Karlsson scores, and physical
      findings supported the positive effect of the procedure. A statistically
      significant positive correlation was found between clinical outcomes and male
      gender, the absence of moderate to severe patellar chondral damage, and
      instability as the dominant preoperative symptom. Postoperative complication rate
      was low and patients with longer postoperative follow-ups demonstrated better
      clinical outcomes. The presented method of tibial tubercle transfer provided a
      good long-lasting surgical solution for patients with patellar instability and
      patients with patellar maltracking and anterior knee pain. Good prognostic
      factors included male gender, clinical patellar instability as the dominant
      preoperative symptom and intact patellar articular cartilage.

PMID- 17429610
TI  - Pullout reattachment of tibial avulsion fractures of the anterior cruciate
      ligament: a firm, effective suture-tying method using a tensioner.
AB  - We describe a firm, effective suture-tying method using a tensioner for
      reattaching tibial avulsion fractures of the anterior cruciate ligament. Our
      simple method achieves strong, firm reattachment of the fracture. In addition, it
      prevents fixation loosening during suture tying effectively. Since pullout repair
      using nonabsorbable sutures is commonly used to fix various avulsion fractures,
      the tensioner helps attain strong, firm reattachment of avulsion fractures simply
      and effectively.

PMID- 17429613
TI  - Mycelial forms of Pseudallescheria boydii present ectophosphatase activities.
AB  - Phosphatase activities were characterized in intact mycelial forms of
      Pseudallescheria boydii, which are able to hydrolyze the artificial substrate p
      nitrophenylphosphate (p-NPP) to p-nitrophenol (p-NP) at a rate of 41.41+/-2.33
      nmol p-NP per h per mg dry weight, linearly with increasing time and with
      increasing cell density. MgCl2, MnCl2 and ZnCl2 were able to increase the (p-NPP)
      hydrolysis while CdCl2 and CuCl2 inhibited it. The (p-NPP) hydrolysis was
      enhanced by increasing pH values (2.5-8.5) over an approximately 5-fold range.
      High sensitivity to specific inhibitors of alkaline and acid phosphatases
      suggests the presence of both acid and alkaline phosphatase activities on P.
      boydii mycelia surface. Cytochemical localization of the acid and alkaline
      phosphatase showed electron-dense cerium phosphate deposits on the cell wall, as
      visualized by electron microscopy. The product of p-NPP hydrolysis, inorganic
      phosphate (Pi), and different inhibitors for phosphatase activities inhibited p
      NPP hydrolysis in a dose-dependent manner, but only the inhibition promoted by
      sodium orthovanadate and ammonium molybdate is irreversible. Intact mycelial
      forms of P. boydii are also able to hydrolyze phosphoaminoacids with different
      specificity.

PMID- 17429611
TI  - A literature review of autograft and allograft anterior cruciate ligament
      reconstruction.
AB  - Knee anterior cruciate ligament reconstructive surgery has significantly evolved
      and now includes the option of using an allograft. This has resulted in numerous
      studies evaluating the advantages and disadvantages of allografts. The purpose of
      this literature review is to evaluate this research and present important
      findings to allow the selection of the most appropriate graft source when
      considering allograft versus autograft reconstruction.

PMID- 17429612
TI  - Effect of thiol redox state modulators on oxidative stress and sclerotial
      differentiation of the phytopathogenic fungus Rhizoctonia solani.
AB  - This study showed that sclerotial differentiation in the filamentous
      phytopathogenic fungus Rhizoctonia solani is directly related to oxidative stress
      and thiol redox state (TRS). Sclerotial differentiation is modulated by the
      availability of non-cytotoxic -SH groups as was shown by the inhibition of
      sclerorial differentiation by the TRS modulator N-acetyl cysteine (AcCSH), and
      not necessarily with those of the TRS reduced components glutathione (GSH) and
      its precursor cysteine (CSH) as indicated by the GSH-biosynthesis inducer and
      inhibitor L-2-oxo-thiazolidine-4-carboxylate and L-buthionine-S,R-sulfoximine,
      respectively. Moreover, inhibition of sclerotial differentiation was accompanied
      by decrease of the high oxidative stress indicators, lipid peroxidation and DNA
      damage in the mycelial substrate where sclerotia initials are formed, which
      suggests that this phenomenon is related to oxidative stress as it is predicted
      by our theory on sclerotial differentiation.

PMID- 17429614
TI  - Isolation of magnetotactic bacterium WM-1 from freshwater sediment and
      phylogenetic characterization.
AB  - The magnetotactic bacterium was isolated from freshwater sediment from North Lake
      of Wuhan. The isolate, designated WM-1, was Gram-negative, helical shaped, and
      studied by means of electron microscopy. The strain WM-1 was 0.2-0.4 microm in
      diameter and 3-4 microm in length. The DNA G + C content was found to be 65.7
      mol%. Phylogenetic analysis of the 16S rDNA gene (Accession number DQ899734 in
      GeneBank) revealed that this isolate was a member ofalphasubdivision of the
      Proteobacteria. Strain WM-1 was closely related (97.7%) to Magnetospirillum sp.
      AMB-1. Randomly amplified polymorphic DNA analysis showed that these two strains
      were in fact different strains. Electron diffraction patterns of WM-1
      magnetosomes indicated that the magnetosomes were composed of magnetite. The
      magnetosomes from WM-1 were cuboidal in shape as observed by electron microscopy.
      Statistical analysis of magnetite crystals from WM-1 showed narrow asymmetric
      size distribution. The average number of magnetosomes in each WM-1 bacterium was
      8 +/- 3.4. The average length of magnetosomes in WM-1 was 54 +/- 12.3 nm and the
      average width is 43 +/- 10.9 nm. These data showed that the grains in WM-1 were
      single-domain crystals.

PMID- 17429615
TI  - Stability of analytes in biosamples - an important issue in clinical and forensic
      toxicology?
AB  - Knowledge of the stability of drugs in biological samples is important for the
      interpretation of toxicological findings. This paper reviews data on the
      stability of drugs in blood, plasma, or serum. Since such data have already been
      reviewed for classic drugs of abuse, the focus here is on newer drugs of abuse
      and on therapeutic drugs. Key information about the conditions of the stability
      experiments will be provided and the following drugs or drug classes are covered:
      amphetamines, amphetamine-derived, piperazine-derived, and phenethylamine-derived
      designer drugs, antidepressants, neuroleptics, anti-HIV drugs, antiepileptics,
      cardiovascular drugs, and others. In addition, aspects of stability experiments
      and their evaluations are discussed. The data presented show that the majority of
      drugs are stable in blood, plasma, or serum samples under the conditions usually
      encountered in a clinical or forensic toxicology laboratory. Instability usually
      only occurs for drugs carrying ester moieties, sulfur atoms, or other easily
      oxidized or reduced structures. Nevertheless, clinical or forensic specimens
      should always be stored at least in the refrigerator and preferably at -20
      degrees C or lower to avoid any degradation. Finally, results obtained from
      biosamples that have been stored at room temperature for a longer time should be
      interpreted with great care and partial degradation should always be considered.

PMID- 17429616
TI  - History of individuals of the 18th/19th centuries stored in bones, teeth, and
      hair analyzed by LA-ICP-MS--a step in attempts to confirm the authenticity of
      Mozart's skull.
AB  - A cranium stored in the Stiftung Mozarteum in Salzburg/Austria which is believed
      to be that of Mozart, and skeletal remains of suspected relatives which have been
      excavated from the Mozart family grave in the cemetery in Salzburg, have been
      subjected to scientific investigations to determine whether or not the skull is
      authentic. A film project by the Austrian television ORF in collaboration with
      Interspot Film on this issue was broadcast at the beginning of the "Mozart year
      2006". DNA analysis could not clarify relationships among the remains and,
      therefore, assignment of the samples was not really possible. In our work this
      skull and excavated skeletal remains have been quantified for Pb, Cr, Hg, As, and
      Sb content by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP
      MS) to obtain information about the living conditions of these individuals. A
      small splinter of enamel (less than 1 mm(3)) from a tooth of the "Mozart cranium"
      was also available for investigation. Quantification was performed by using
      spiked hydroxyapatite standards. Single hair samples which are recorded to
      originate from Mozart have also been investigated by LA-ICP-MS and compared with
      hair samples of contemporary citizens stored in the Federal Pathologic-Anatomical
      Museum, Vienna. In general, Pb concentrations up to approximately 16 mug g(-1)
      were found in the bone samples of 18th century individuals (a factor of 7 to 8
      higher than in recent samples) reflecting elevated Pb levels in food or
      beverages. Elevated Pb levels were also found in hair samples. The amount of Sb
      in the enamel sample of the "Mozart cranium" (approx. 3 mug g(-1)) was
      significantly higher than in all the other tooth samples investigated, indicating
      possible Sb ingestion in early childhood. Elevated concentrations of elements in
      single hair samples gave additional information about possible exposure of the
      individuals to heavy metals at a particular point in their life.

PMID- 17429617
TI  - Mitochondrial respiratory inhibition and oxidative stress elevate beta-secretase
      (BACE1) proteins and activity in vivo in the rat retina.
AB  - Cerebral hypometabolism, oxidative stress and beta-amyloid peptide (Abeta)
      accumulation are key pathological events in Alzheimer's disease (AD). Beta
      secretase (BACE, i.e., BACE1), a prerequisite for Abeta genesis, is elevated in
      sporadic AD. Recent studies show BACE upregulation in experimental conditions
      likely associated with energy insufficiency and/or oxidative stress. We
      investigated the effect of sublethal doses of mitochondrial respiratory
      inhibitors and potential endogenous oxidative substances on BACE expression in
      vivo using the retina as a model. Retinas were analyzed biochemically and
      anatomically 48 h following intraocular applications of mitochondrial complex I,
      II and IV inhibitors including rotenone, 3-nitropropionic acid and sodium azide,
      and plaque-containing oxidants including Fe(3+) and Abeta42 fibrils (Abeta42f).
      All agents caused elevations of BACE proteins and beta-site amyloid precursor
      protein (APP) cleavage product, beta-CTF, in retinal lysates in a dose-dependant
      manner. BACE activity and Abeta40 levels were also increased in agent-treated
      retinas relative to vehicle controls. BACE immunoreactivity in normal adult rat
      retina was present mostly in the plexiform layers, indicating a localization of
      the enzyme to synaptic terminals. No apparent change in laminar or cellular
      distribution of BACE labeling was detected in the experimental retinas. However,
      signs of neuronal stress including glial activation were observed in agent
      treated retinas especially in high dosage groups. Our data suggest that
      mitochondrial respiratory inhibition and oxidative stress facilitate BACE
      expression in vivo. In addition, plaque constituents such as Fe(3+) and Abeta42f
      may participate in a self-enforcing cycle of amyloidogenesis via BACE
      upregulation.

PMID- 17429619
TI  - Environment effects on the oscillatory unfolding kinetics of GFP.
AB  - The chromophore of a green fluorescent protein (GFP) mutant engineered to enhance
      emission and stability is known to display erratic switchings among a few of its
      chemical substates and, in particular, between the anionic A and the neutral N
      substates, whose difference is associated with a proton exchange and a consequent
      conformation rearrangement. However, when close to unfolding, the A-N switchings
      suddenly become very regular as shown by fluorescence oscillations that have been
      recently observed for molecules embedded in wet silica gel. In order to establish
      whether the matrix hosting the protein is responsible for these oscillations, we
      investigated the effect of another medium (silanized surfaces), of a different
      denaturant (urea) and of cosolvents (D(2)O and glycerol). The occurrence of
      periodic A-N switchings, in the last milliseconds before GFP unfolding, is
      observed under all investigated conditions, together with three specific
      frequency values that characterize the pre-unfolding fluorescence. Urea and
      guanidinium, the denaturants employed in order to unfold GFP, do not lead to
      appreciable differences in the observed switching parameters, whereas the
      different media embedding the protein give rise only to frequency shifts that
      scale with the viscosity of the host. The periodicity of the GFP A-N switchings
      and their dependence on cosolvents suggest that they could be associated with
      oscillatory motions between meta-stable conformations of the beta-barrel
      surrounding the chromophore near protein unfolding.

PMID- 17429618
TI  - The effect of short-term changes in the body mass on anticipatory postural
      adjustments.
AB  - The purpose of the study was to investigate whether anticipatory postural
      adjustments (APAs) are modified with short-term changes in the body mass. Nine
      subjects were asked to catch a 2.2 kg load with their arms extended under
      conditions of no weight and when additional weights of 10 and 20% of the
      subject's body weight (BW) were attached to single body locations or when 20 or
      40% BW were attached evenly to two locations. Attaching weights was associated
      with an increase of the whole body mass, but also involved changes in the
      vertical position of the center of mass (COM). Electromyographic activity of leg
      and trunk muscles and ground reaction forces were recorded and quantified within
      the typical time intervals of APAs. APAs were influenced by the magnitude of the
      weight attached to the body: an increase in the body mass was associated with
      anticipatory co-activation of trunk and leg muscles. The level of this co
      activation increased with an increase in the magnitude of weight added to the
      body. At the same time, APAs were affected by the changes in the vertical
      position of COM. These findings suggest that in the case of short-term changes in
      the body mass, the CNS might prioritize information regarding the magnitude and
      location of the additional weight added to the body and utilize a strategy of
      anticipatory co-activation of postural muscles directed at the stabilization of
      body segments.

PMID- 17429620
TI  - Characterization of polysaccharide hydrogels for modified drug delivery.
AB  - Hydrogels are hydrophilic macromolecular networks that are capable of retaining a
      large amount of water. A precise description of these systems is actually quite
      complex and the practical use of hydrogels for drug delivery and biomedical
      applications is often not supported by a well-defined knowledge of the overall
      structure of the polymeric network. In this paper, we report the characterization
      of two different systems: a chemical network based on Guar Gum (GG) and a
      physical gel prepared with Xanthan (Xanth) and Locust Bean Gum (LBG). The dynamo
      mechanical properties of the gels were analysed: the cohesiveness and the
      adhesion of the networks were strongly dependent on time, temperature, and
      composition. The kinetics of the chemical crosslinking was followed by means of
      rheological measurements, i.e. recording the mechanical spectra of the gelling
      system, and the power law exponent at the gel point was evaluated. Furthermore,
      the networks, loaded with model drugs with different steric hindrance, were used
      as matrices for tablets and the rate of release of such model drugs was studied.
      The diffusion of the guest molecules was deeply dependent on their dimensions; in
      the case of Xanth-LBG tablets the release profiles were almost independent from
      the different cohesion properties of the starting hydrogel composition.

PMID- 17429621
TI  - Structural characterization of heterodimeric laccases from Pleurotus ostreatus.
AB  - The subfamily of POXA3 laccase isoenzymes produced by the fungus Pleurotus
      ostreatus has been characterized as an example of the complexity and
      heterogeneity of fungal isoenzyme patterns. Two isoenzymes, POXA3a and POXA3b,
      were previously purified, exhibiting an unusual heterodimeric structure composed
      of a large (67 kDa) and a small (18 or 16 kDa) subunit. A unique gene encodes the
      large subunit of both POXA3a and POXA3b, but alternative splicing produces two
      variants--differing for an insertion of four amino acids--for each isoenzyme. Two
      genes encoding POXA3a and POXA3b small subunits have been identified, and the
      corresponding amino acid sequences show only two amino acid substitutions. The 18
      and 16-kDa subunits of both POXA3a and POXA3b differ for N-glycosylation at
      Asn150 of the 16-kDa subunit. The POXA3 large subunit 3D model allows us to
      highlight peculiarities of this molecule with respect to the laccases whose 3D
      structures are known.

PMID- 17429622
TI  - Femoral component malrotation and arthrofibrosis after total knee arthroplasty:
      cause and effect relationship?

PMID- 17429624
TI  - A case of drug resistant clear cell ovarian cancer showing responsiveness to
      gemcitabine at first administration and at re-challenge.
AB  - INTRODUCTION: Gemcitabine (2',2'-difluorodeoxycytidine) (GEM) has been
      demonstrated to be active in the salvage setting of ovarian cancer (OC) patients.
      CASE REPORT: A 57-year-old woman, with a diagnosis of FIGO Stage IIIC clear cell
      OC, judged inoperable to optimal residual tumor, was administered neo-adjuvant
      chemotherapy with carboplatin/paclitaxel/topotecan, and cytoreduction. After 5
      months the patient progressed, and pegylated liposomal doxorubicin was started
      with rapid progression. GEM (1,000 mg/m2, d1,8,15, q28) was then started, and a
      complete clinical response was documented after seven cycles of treatment, and
      was maintained for 9 months; at progression fourth line carboplatin was attempted
      but 1 month after the last course of carboplatin, progression occurred, and the
      patient was re-challenged with GEM obtaining a partial response, of 6 months
      duration. Currently, the patient is still under treatment, without any complaints
      relative to her quality of life/specific symptoms. CONCLUSION: We described the
      case of a drug resistant clear cell ovarian cancer showing a selective
      susceptibility only to GEM at first administration and at re-challenge. Moreover,
      this case expressed a molecular profile very likely to support high tumour cell
      sensitivity to GEM.

PMID- 17429623
TI  - Phase I and pharmacokinetic study of UCN-01 in combination with irinotecan in
      patients with solid tumors.
AB  - PURPOSE: 7-Hydroxystaurosporine (UCN-01) is a protein kinase inhibitor that
      inhibits several serine-threonine kinases including PKC and PDK1. Due to the
      preclinical synergistic effects seen with topoisomerase I inhibitors and non
      overlapping toxicity, UCN-01 and irinotecan were combined in a dose-finding study
      designed to determine the maximum tolerated dose (MTD), toxicity profile, and
      pharmacokinetics (PK) of UCN-01 and irinotecan. METHODS: Patients with incurable
      solid malignancies received UCN-01 intravenously (IV) as a 3-h infusion on day 1
      and irinotecan IV over 90 min on days 1 and 8 of a 21-day cycle. Doses of UCN-01
      for subsequent cycles were half the starting dose. Dose level 1 (DL1) consisted
      of UCN-01 and irinotecan doses of 50 and 60 mg/m(2), respectively. Blood samples
      were collected in cycle 1 for UCN-01, irinotecan, and irinotecan metabolites.
      RESULTS: A total of 16 patients were enrolled on the trial at UCN-01/Irinotecan
      doses of 50/60 mg/m(2) (DL1; n = 1), 70/60 mg/m(2) (DL2; n = 6), 90/60 mg/m(2)
      (DL3; n = 4), and 70/90 mg/m(2) (DL4; n = 5). Two dose-limiting toxicities were
      observed each in DL3 and DL4 (2 grade 3 hypophosphatemia, 1 grade 4 hyperglycemia
      and grade 3 hypophosphatemia, 1 grade 4 febrile neutropenia). Fatigue, diarrhea,
      nausea, and anorexia were the most prevalent toxicities. No objective responses
      were documented, and four patients had stable disease for at least ten cycles.
      The long half-life (292.0 +/- 135.7 h), low clearance (0.045 +/- 0.038 l/h), and
      volume of distribution (14.3 +/- 5.9 l) observed for UCN-01 are consistent with
      prior UCN-01 data. There was a significant decrease in C(max) of APC, AUC of APC
      and SN-38, and AUC ratio of SN-38:irinotecan when comparing days 1 and 8 PK.
      CONCLUSIONS: APC and SN-38 exposure decreased when administered in combination
      with UCN-01. The MTD of the combination based on protocol criteria was defined as
      70 mg/m(2) of UCN-01 on day 1 and 60 mg/m(2) of irinotecan on days 1 and 8 in a
      21-day cycle.

PMID- 17429625
TI  - Preclinical pharmacokinetics and in vitro metabolism of dasatinib (BMS-354825): a
      potent oral multi-targeted kinase inhibitor against SRC and BCR-ABL.
AB  - PURPOSE: Dasatinib (BMS-354825), a potent oral multi-targeted kinase inhibitor
      against SRC and BCR-ABL, has recently been approved for the treatment of chronic
      myelogenous leukaemia (CML) in imatinib-acquired resistance and intolerance. In
      vitro and in vivo studies were conducted to characterize the pharmacokinetics and
      metabolism of dasatinib in mouse, rat, dog, and monkey. Possible mechanisms
      contributing to the incomplete oral bioavailability of dasatinib in animals were
      investigated. METHODS: Metabolic stability of dasatinib was measured after
      incubation with liver microsomes (either NADPH- or UDPGA-fortified) and isolated
      hepatocytes obtained from mouse, rat, dog, monkey, and human. In all cases,
      substrate depletion over time was measured, and appropriate scaling factors were
      used to predict in vivo clearance. Pharmacokinetics of dasatinib were determined
      in mice, rats, dogs, and monkeys after administration of single intravenous or
      oral doses. In addition, the routes of excretion were investigated after
      administration of dasatinib to bile duct cannulated (BDC) rats. Absorption and
      first-pass metabolism were evaluated as possible reasons for the incomplete oral
      bioavailability using various in vitro and in vivo models like Caco-2 cells, P
      glycoprotein (P-gp) knockout mice, and intra-portal dosing in rats. RESULTS: In
      vivo systemic plasma clearance values of dasatinib were 62, 26, 25, and 34
      ml/min/kg in mouse, rat, dog, and monkey, respectively. Scaling of in vitro
      hepatocyte and liver microsomal data gave reasonably good predictions of in vivo
      clearances across all species. Percent distribution in blood cells ranged from
      43% in mouse to 57% in dog. Dasatinib showed high volumes of distribution (>3
      l/kg) and high serum protein binding values (>90%) in all four species tested.
      Oral bioavailability of dasatinib ranged from 14% in the mouse to 34% in the dog.
      In rats, bioavailability after an intraportal dose was comparable to that after
      intra-arterial administration. In BDC rats, less than 15% of an intravenous dose
      was excreted unchanged in urine, bile, and the gastrointestinal tract, suggesting
      that dasatinib is cleared primarily via metabolism. Dasatinib has high intrinsic
      permeability in Caco-2 cells, however, the efflux ratio was approximately two
      fold indicating that it may be a substrate for an intestinal efflux transporter.
      However, in vivo studies in P-gp knockout mice versus wild-type mice showed no
      difference in the amount of dasatinib remaining unabsorbed in the
      gastrointestinal tract, suggesting that P-gp may not be responsible for the
      incomplete bioavailability. CONCLUSIONS: Dasatinib shows intermediate clearance
      in mouse, rat, dog, and monkey, and distributes extensively in those species.
      Oxidative metabolism appears to be the predominant clearance pathway. The
      incomplete oral bioavailability may be due to both incomplete absorption and high
      first-pass metabolism. However, the efflux transporter, P-glycoprotein does not
      appear to be limiting oral absorption.

PMID- 17429626
TI  - Prognostic factors for survival of patients with advanced gastric cancer treated
      with cisplatin-based chemotherapy.
AB  - PURPOSE: The present study evaluated baseline patient- or tumor-related
      prognostic factors in patients with advanced gastric adenocarcinoma. PATIENTS AND
      METHODS: A total of 304 consecutive patients with newly diagnosed metastatic or
      recurrent gastric cancer treated with one or more cycles of cisplatin-based
      chemotherapy at the Korea Cancer Center Hospital were enrolled in the current
      study. RESULTS: Among the original 304 patients, only 4 patients were alive at
      the time of this analysis. The median survival for all patients was 7.3 (95% CI,
      6.3-8.2) months. Five independent prognostic factors were identified by a
      multivariate analysis: poor performance status (hazard ratio [HR], 1.46; 95% CI,
      1.32-2.92), elevated total bilirubin (HR, 2.04; 95% CI, 1.73-2.35), presence of
      peritoneal metastasis (HR, 1.73; 95% CI, 1.57-1.90), presence of bone metastasis
      (HR, 3.11; 95% CI, 2.69-3.53), and more than 1 metastatic site (HR, 1.22; 95% CI,
      1.06-1.38). A prognostic index was constructed that divided the patients into a
      good (n = 162), moderate (n = 82), or poor (n = 60) risk group. The 1-year
      survival rates for the good, moderate, and poor risk groups were 34.6, 20.7, and
      1.7%, respectively, and the survival differences among the groups were highly
      significant (P < 0.0001). CONCLUSION: Five prognostic factors were identified
      from patients receiving first-line cisplatin-based chemotherapy for advanced
      gastric cancer. A simple prognostic index was then developed that produced
      distinct survival rates among the different risk groups. Therefore, this
      prognostic model could help clinicians and patients in clinical decision-making
      and treatment tailoring based on the estimated prognosis.

PMID- 17429627
TI  - A novel N-alkylated prodigiosin analogue induced death in tumour cell through
      apoptosis or necrosis depending upon the cell type.
AB  - PURPOSE: To investigate the mechanism of cell death induced by the N-alkylated
      prodigiosin analogue, 2,2'-[3-methoxy-1'amyl-5'-methyl-4-(1''-pyrryl)] dipyrryl
      methene (MAMPDM) in S-180 and EL-4 tumour cell lines. METHODS: Effect of MAMPDM
      on cell viability was assessed by MTT dye conversion. Induction of apoptosis was
      assessed by monitoring caspase 3 activity using a fluorogenic substrate,
      fragmentation of DNA by gel electrophoresis and sub-diploid DNA containing cells
      by flowcytometry. Necrosis was estimated by flowcytometric analysis of the uptake
      of propidium iodide. RESULTS: MAMPDM inhibited the proliferation of murine
      fibrosarcoma, S-180 cells and induced cell death. Investigations into the
      mechanism of cell death by MAMPDM in S-180 cells showed absence of hallmarks of
      apoptotic cell death such as activation of caspase 3, DNA fragmentation and
      presence of cells with sub-diploid DNA content. However, there was a rapid loss
      of membrane integrity as assessed by uptake of propidium iodide, which is
      characteristic of necrosis. In contrast to induction of necrosis in S-180 cells,
      MAMPDM induced apoptotic cell death in EL-4 cells as evident by activation of
      caspase 3, fragmentation of DNA and sub-diploid DNA containing cells.
      CONCLUSIONS: MAMPDM could induce cell death by either apoptosis or necrosis
      depending upon the cell type. This would be of advantage in elimination of tumor
      cells defective in apoptotic pathway and therefore, refractory to the
      conventional therapies.

PMID- 17429628
TI  - Pharmacodynamic characterization of gemcitabine cytotoxicity in an in vitro cell
      culture bioreactor system.
AB  - PURPOSE: Gemcitabine, a pyrimidine nucleoside, is approved for the treatment of
      non-small cell lung cancer, pancreatic carcinoma, and breast cancer. Chemotherapy
      regimens are determined experimentally with static tissue culture systems, animal
      models, and in Phase I clinical trials. The aim of this study was to assess for
      gemcitabine-induced cell death following infusion of drug under clinically
      relevant conditions of infusion rate and drug exposure in an in vitro bioreactor
      system. METHODS: To estimate an appropriate harvest time for cells from the
      bioreactor after drug treatment, we estimated the temporal relationship between
      gemcitabine treatment for 1 h and cell death at a later time point with monolayer
      growth assays (i.e., static culture). Afterward, 5.3 mg gemcitabine was infused
      over 0.5 h in the bioreactor, followed by mono-exponential decay, simulating
      patient concentration-time profiles (n = 4). Controls were run with drug-free
      media (n = 4). Cells were harvested from the bioreactor at a later time point and
      assessed for cell death by flow cytometry. RESULTS: According to monolayer growth
      assay results, cytotoxicity became more apparent with increasing time. The E Max
      for cells 48 h after treatment was 50% and after 144 h, 93% (P = 0.022; t test),
      while flow cytometry showed complete DNA degradation by 120 h. Gemcitabine was
      infused in the bioreactor. The gemcitabine area under the concentration-time
      curve (AUC) was 56.4 microM h and the maximum concentration was 87.5 +/- 2.65
      microM. Flow cytometry results were as follows: the G1 fraction decreased from
      65.1 +/- 4.91 to 28.6 +/- 12% (P = 0.005) and subG1 increased from 14.1 +/- 5.28
      to 42.6 +/- 9.78% (P = 0.004) relative to control. An increase in apoptotic cells
      was observed by TUNEL assay. CONCLUSIONS: The in vitro bioreactor system will be
      expanded to test additional cell lines, and will serve as a useful model system
      for assessing the role of drug pharmacokinetics in delivery of optimized
      anticancer treatment.

PMID- 17429629
TI  - Phase-II study of dose attenuated schedule of irinotecan, capecitabine, and
      celecoxib in advanced colorectal cancer.
AB  - BACKGROUND: The cyclooxygenase-2 (COX-2) enzyme plays a major role in tumor
      progression and resistance to chemotherapy. A Phase-II study was undertaken to
      determine the activity of a dose attenuated schedule of irinotecan, capecitabine,
      and the COX-2 inhibitor celecoxib in patients with advanced colorectal cancer.
      METHODS: The eligibility criteria included a pathologically or cytologically
      confirmed diagnosis of adenocarcinoma of the colon or rectum that was metastatic.
      Patients received a combination of irinotecan 70 mg/m2 over 30 min I.V. on days 1
      and 8, capecitabine 1,000 mg/m2 twice per day orally on days 1-14, and celecoxib
      at a daily dose of 800 mg continuously. Cycles were repeated every 21 days.
      RESULTS: Fifty-one patients were enrolled (median age 58 years; M : F 31 : 20).
      The objective response rate was 21/51 = 41% [95% confidence intervals (CI), 0.28
      0.55]. The median time to progression was 7.7 months (95% CI, 6.2-8.6 months).
      Median survival time and probability of survival at 1 year were 21.2 months (95%
      CI, 13.8-n/a), and 75% (95% CI, 0.63-0.88), respectively. The major toxicity was
      Grade 3 or 4 diarrhea, seen in 24 and 10% of patients, respectively. There were
      no treatment related deaths. CONCLUSIONS: The lower dose intensity of irinotecan
      appeared to maintain activity and improve tolerability when combined with
      capecitabine. The addition of celecoxib to irinotecan and capecitabine did not
      appear to significantly increase the activity of this doublet based on the RECIST
      criteria for objective response.

PMID- 17429630
TI  - A phase II study of irinotecan in combination with doxifluridine, an intermediate
      form of capecitabine, in patients with metastatic colorectal cancer.
AB  - The purpose of this study was to examine the efficacy of a combination treatment
      of sequential irinotecan and doxifluridine, an intermediate of capecitabine,
      evaluated by the response rate and safety in patients with metastatic colorectal
      cancer. In all, 60 metastatic colorectal cancer patients with measurable disease
      were enrolled. The schedule of the treatment consisted of a 90 min intravenous
      (IV) infusion of irinotecan 150 mg/m2 for on days 1 and 15, and 600-1,000 mg/body
      of oral doxifluridine on days 3-14 and 17-28. Cycles were repeated every 35 days.
      A median of three cycles of the combination therapy (range 1-14 cycles) was
      administered. A total of 57 patients (95%) completed at least two cycles of the
      therapy without any dose reductions. There was one complete response and 23
      partial responses with an overall response rate of 40% [95% confidence interval
      (CI): 28-53%]. A total of 19 patients had stable disease, 43(72%) achieved
      disease control. The median time to progression was 5.9 months and the median
      overall survival was 20.5 months. Ten (17%) and 17 (28%) patients developed Grade
      3-4 leukopenia and neutropenia, respectively. Grade 3-4 fatigue was observed in
      7(12%) patients, nausea in five (8%), vomiting in four (7%), and diarrhea,in
      three (5%) patients. No treatment-related deaths were noted during the study.
      From these results, the combination of sequential irinotecan and doxifluridine is
      considered to be an effective, easy-to-administer regimen with acceptable
      tolerability.

PMID- 17429632
TI  - Neurotoxicity of FOLFOX-4 as adjuvant treatment for patients with colon and
      gastric cancer: a randomized study of two different schedules of oxaliplatin.
AB  - PURPOSE: The dose limiting toxicity of oxaliplatin (l-HOP) is neurotoxicity,
      which is characterized by an acute neuropathy and a clinically distinct chronic
      neuropathy. This randomized study evaluated if prolonged l-HOP infusion over the
      conventional l-HOP schedule was useful in reducing acute and possibly chronic l
      HOP induced neurotoxicity in colon and gastric cancer patients receiving l-HOP
      based regimen as adjuvant chemotherapy. METHODS: Sixty-four patients were
      randomly assigned to group A (26 colon and 6 gastric cancer) and to group B (23
      colon and 9 gastric cancer). Chemotherapy in both groups consisted of l-HOP 85
      mg/m(2) i.v. only on day 1, with leucovorin 100 mg/m(2) i.v. as a 2-h infusion
      followed by bolus 5-fluorouracil (5-FU) 400 mg/m(2)/day and a 22-h infusion of 5
      FU 600 mg/m(2)/day, repeated for two consecutive days every 2 weeks for a maximum
      of 12 cycles. Patients in group A received l-HOP as a continuous 6-h i.v.
      infusion, and patients in group B received l-HOP as the conventional 2-h i.v.
      infusion. RESULTS: The percentage of patients presenting with grade >/=2
      neurotoxicity was statistically lower in group A than in group B (28.1% vs.
      59.3%: P = 0.02). There was a statistically lower percentage of cycles with grade
      >/=2 neurotoxicity in group A (6.1%) than in group B (18.5%) (P < 0.001).
      CONCLUSIONS: This study suggests that l-HOP as a continuous 6-h infusion is
      useful in preventing and reducing acute l-HOP induced neurotoxicity in patients
      with colon and gastric cancer receiving FOLFOX-4 regimen as adjuvant treatment.

PMID- 17429631
TI  - Lysosomotropic acid ceramidase inhibitor induces apoptosis in prostate cancer
      cells.
AB  - PURPOSE: Alterations in ceramide metabolism have been reported in prostate cancer
      (PCa), resulting in escape of cancer cells from ceramide-induced apoptosis.
      Specifically, increased expression of lysosomal acid ceramidase (AC) has been
      shown in some primary PCa tissues and in several PCa cell lines. To determine if
      this represents a novel therapeutic target, we designed and synthesized LCL204, a
      lysosomotropic analog of B13, a previously reported inhibitor of AC METHODS:
      Prostate cancer cell lines were treated with LCL204 for varying times and
      concentrations. Effects of treatment on cytotoxicity, sphingolipid content, and
      apoptotic markers were assessed. RESULTS: Treatment of DU145 PCa cells resulted
      in increased ceramide and decreased sphingosine levels. Interestingly, LCL204
      caused degradation of AC in a cathepsin-dependent manner. We also observed rapid
      destabilization of lysosomes and the release of lysosomal proteases into the
      cytosol following treatment with LCL204. Combined, these events resulted in
      mitochondria depolarization and executioner caspase activation, ultimately ending
      in apoptosis CONCLUSIONS: These results provide evidence that treatment with
      molecules such as LCL204, which restore ceramide levels in PCa cells may serve as
      a new viable treatment option for PCa.

PMID- 17429633
TI  - Revision of the theory of tracer transport and the convolution model of dynamic
      contrast enhanced magnetic resonance imaging.
AB  - Counterexamples are used to motivate the revision of the established theory of
      tracer transport. Then dynamic contrast enhanced magnetic resonance imaging in
      particular is conceptualized in terms of a fully distributed convection-diffusion
      model from which a widely used convolution model is derived using, alternatively,
      compartmental discretizations or semigroup theory. On this basis, applications
      and limitations of the convolution model are identified. For instance, it is
      proved that perfusion and tissue exchange states cannot be identified on the
      basis of a single convolution equation alone. Yet under certain assumptions,
      particularly that flux is purely convective at the boundary of a tissue region,
      physiological parameters such as mean transit time, effective volume fraction,
      and volumetric flow rate per unit tissue volume can be deduced from the kernel.

PMID- 17429634
TI  - An equation-free approach to analyzing heterogeneous cell population dynamics.
AB  - We propose a computational approach to modeling the collective dynamics of
      populations of coupled, heterogeneous biological oscillators. We consider the
      synchronization of yeast glycolytic oscillators coupled by the membrane exchange
      of an intracellular metabolite; the heterogeneity consists of a single random
      parameter, which accounts for glucose influx into each cell. In contrast to Monte
      Carlo simulations, distributions of intracellular species of these yeast cells
      are represented by a few leading order generalized Polynomial Chaos (gPC)
      coefficients, thus reducing the dynamics of an ensemble of oscillators to
      dynamics of their (typically significantly fewer) representative gPC
      coefficients. Equation-free (EF) methods are employed to efficiently evolve this
      coarse description in time and compute the coarse-grained stationary state and/or
      limit cycle solutions, circumventing the derivation of explicit, closed-form
      evolution equations. Coarse projective integration and fixed-point algorithms are
      used to compute collective oscillatory solutions for the cell population and
      quantify their stability. These techniques are extended to the special case of a
      "rogue" oscillator; a cell sufficiently different from the rest "escapes" the
      bulk synchronized behavior and oscillates with a markedly different amplitude.
      The approach holds promise for accelerating the computer-assisted analysis of
      detailed models of coupled heterogeneous cell or agent populations.

PMID- 17429635
TI  - [Immunohistochemical sex cord markers. Description and use in the differential
      diagnosis of ovarian tumors].
AB  - Sex cord markers comprise proteins and hormones that are produced in sex cord
      derivatives in normal ovaries and testes as well as in gonadal sex cord-stromal
      tumors. Sex cord markers (e.g. inhibin-alpha) are used clinically as serum tumor
      markers. Immunohistochemical staining of sex cord markers may be helpful in the
      differential diagnosis of ovarian sex cord-stromal tumors versus surface
      epithelial-stromal tumors, germ cell tumors, other ovarian tumors, and ovarian
      metastases. Inhibin-alpha has been shown to be the most specific marker of sex
      cord differentiation. In comparison, calretinin is a somewhat more sensitive
      albeit less specific marker. Currently, an immunohistochemical panel including
      inhibin-alpha and calretinin is considered most helpful in the differential
      diagnosis of ovarian sex cord-stromal tumors. CD99, Mullerian inhibiting
      substance (MIS), melan A and CD10, being sex cord markers of limited sensitivity
      and specificity, should only be used as part of an antibody panel in specific
      diagnostic settings. EMA, CK7 and chromogranin are considered additional markers
      that may be useful in the differential diagnosis of ovarian sex cord-stromal
      tumors.

PMID- 17429636
TI  - Eight versus 16-week re-evaluation period in rheumatoid arthritis patients
      treated with leflunomide or methotrexate accompanied by moderate dose prednisone.
AB  - In a step-up approach of DMARD treatment of RA a fast response and an early DMARD
      switch in the case of non-response is important. Therefore, we performed an open
      trial in which we compared an 8-week and a 16-week observation period during
      treatment of RA with MTX or LEF, both given in intensified starting doses and
      accompanied by moderate dose prednisone. MTX and LEF naive patients with RA (mean
      time since diagnosis: 2.3 years) were randomised to receive either LEF in a 3-day
      loading dose of 100 mg/day followed by 20 mg/day (n = 19) or MTX intramuscularly
      in a dose of 25 mg once weekly (n = 21). All patients received concomitant
      treatment with oral prednisone in an initial dose of 20 mg/day with weekly dose
      reductions of 5 mg/day. The disease activity was re-evaluated 8 and 16 weeks
      after the start of the treatment. Mean DAS28 before the start of treatment was
      5.36 +/- 0.8 for the MTX-group and 5.46 +/- 0.8 for the LEF-group. After 8 weeks
      of treatment the DAS28 in the MTX-group was 2.59 +/- 1.0 and 3.16 +/- 0.8 in the
      LEF group (difference not significant). The mean DAS28 at re-evaluation 16 weeks
      after the starting of treatment (2.58 +/- 1.5 for the MTX-group and 3.25 +/- 1.16
      for the LEF-group) was significantly different neither in between the both
      treatment groups nor in comparison to the week 8 evaluation. Efficiency of RA
      treatment with MTX or LEF in intensified doses and in combination with moderate
      dose prednisone can be sufficiently judged 8 weeks after its initiation.

PMID- 17429637
TI  - Development of acute inflammatory arthritis by granulocyte-macrophage colony
      stimulating factor during autologous stem cell transplantation for
      cryoglobulinemia.
AB  - Hematopoietic growth factors (HGFs) are now known to influence the function of
      mature myeloid cells as well as their traditional roles as regulators of
      hematopoiesis. It became apparent that they could take part in inflammatory and
      immune responses by activating monocytes/macrophages to release mediators of such
      responses. We describe a 53-year-old male who developed acute inflammatory
      arthritis by granulocyte-macrophage colony-stimulating factor (GM-CSF) following
      autologous stem cell transplantation for cryoglobulinemia. Arthritis improved
      dramatically soon after GM-CSF was withdrawn and steroid therapy was admitted.
      This case may lead to further attention for this potential problem since HGFs are
      frequently used in a variety of clinical settings.

PMID- 17429638
TI  - Predicting factors for severity of rheumatoid arthritis: a prospective
      multicenter cohort study of 172 patients over 3 years.
AB  - Rheumatoid arthritis may take an unfavourable course leading to rapid functional
      decline in a certain percentage of patients. Early identification of these
      patients is desirable. The aim of this study was to evaluate clinical and
      laboratory parameters for their value in the prediction of bad outcome. A total
      of 172 patients with early arthritis were followed for 3 years. Higher initial
      values for erythrocyte sedimentation rate, IgG and IgM rheumatoid factor, serum
      concentration of cartilage oligomeric matrix protein, Health Assessment
      Questionnaire score, Larsen score of feet, disease activity score, and swollen
      and tender joint count predicted worse outcome. An association with the presence
      of IgA rheumatoid factor or anti-cyclic-citrullinated peptide could not be
      established. We conclude that prognosis in an individual with rheumatoid
      arthritis depends on many factors. The determination of independent prognostic
      factors for progression of rheumatoid arthritis is a valuable tool in early
      arthritis to select patients for more aggressive therapy.

PMID- 17429639
TI  - Nephrotic syndrome as a clinical manifestation of systemic sclerosis.
AB  - We have described the unusual case of coexistence of membranous nephropathy
      resulting in nephrotic syndrome with systemic sclerosis. A 60-year-old patient
      was admitted to the Department of Nephrology with marked proteinuria and oedema.
      The renal biopsy specimen disclosed the features characteristic of membranous
      glomerulonephritis. The patient was treated with chlorambucil for 1 month
      followed by prednisone for 1 month. However, her condition still did not improve.
      Therefore, the other causes of nephrotic syndrome were investigated. Once anti
      Scl-70 antibody was detected the patient was transferred to the Department of
      Rheumatology and Connective Tissue Diseases. Physical examination revealed
      Raynaud phenomenon, sclerodactylia, thickened skin of the chest and back. The
      patient was diagnosed with diffuse systemic sclerosis. The cyclophosphamide
      therapy was instituted and the patient's condition improved.

PMID- 17429641
TI  - MDCT urography: experience with a bi-phasic excretory phase examination protocol.
AB  - The benefit of multidetector computed tomographic urography (MDCTU) for
      visualising early and late excretory phase (EP) upper urinary tract (UUT)
      opacification has been studied. UUT opacification was retrospectively evaluated
      in 45 bi-phasic four-row MDCTU examinations. The UUT was divided into intrarenal
      collecting system (IRCS), proximal, middle and distal ureter. Two independent
      readers rated opacification: 1, none; 2, partial; 3, complete. Numbers of
      segments and percentages of UUTs at each score were calculated for each EP and
      two EPs combined. Results of a single EP and of combined EPs were compared by
      Wilcoxon matched-pairs signed-ranks. IRCS and proximal ureter were at least
      partially opacified in each EP in >95%. The middle ureter was at least partially
      opacified in the early and late EP in 85% and 93%, respectively. The distal
      ureter was opacified in 65% (49/75) in the early EP and in 78% (59/75) in the
      late EP. Combining two EPs, non-opacified distal segments decreased to 9% (7/75).
      Significant improvement between a single EP and combining two EPs were found for
      the middle and distal ureter (P < 0.03). Bi-phasic MDCTU substantially improved
      opacification of the middle and distal ureter. IRCS and proximal ureter are
      reliably opacified with one EP.

PMID- 17429640
TI  - Biliary and reticuloendothelial impairment in hepatocarcinogenesis: the
      diagnostic role of tissue-specific MR contrast media.
AB  - The development and progression of a hepatocellular carcinoma (HCC) in a
      chronically diseased liver, i.e., the carcinogenesis, comprise a multistep and
      long-term process. Morphologically, this process is associated with the presence
      of distinct nodular lesions in the liver that are called 'preneoplastic lesions.'
      These preneoplastic lesions are associated with and can precede the growth and
      progression of well-differentiated HCCs . The characterization of nodular lesions
      and demonstration of the multistep development of HCC in the cirrhotic liver by
      imaging modalities represent a challenging issue. The arterial hypervascular
      supply, depicted by different dynamic studies, represents a fundamental
      radiological criterion for the diagnosis of HCC in cirrhosis. Magnetic resonance
      (MR) imaging performed with tissue-specific contrast media can help to
      investigate the "grey area" of carcinogenesis, in which significant histological
      changes are already present without any imaging evidence of neoangiogenesis. The
      purpose of this review is to provide information on the properties of tissue
      specific MR contrast agents and on their usefulness in the demonstration of the
      pathologic changes that take place at the level of the biliary and
      reticuloendothelial systems during the carcinogenetic process in liver cirrhosis.

PMID- 17429642
TI  - Focal interstitial fibrosis manifesting as nodular ground-glass opacity: thin
      section CT findings.
AB  - The purpose of this study was to describe the thin-section computed tomographic
      (CT) features of focal interstitial fibrosis manifesting as nodular ground-glass
      opacity (GGO) and its changes during follow-up. The thin-section CT findings of
      pathologically proven focal interstitial fibrosis manifesting as nodular GGO were
      retrospectively evaluated in nine patients (five women and four men; mean age,
      59.3 years; age range, 34-81 years). The thin-section CT findings of each lesion
      were analyzed for multiplicity, location, shape, margin characteristics, pleural
      retraction or vascular convergence, size and internal attenuation, lesion
      internal features and lesion changes on follow-up CT scans (mean 90 days, range 5
      to 215 days). All lesions manifested as a solitary nodular GGO (100%), and seven
      of the nine lesions (77.8%) were located in the upper lobe. Focal interstitial
      fibrosis was round or oval in shape in five cases (55.6%), complex in shape in
      three cases (33.3%) and polygonal in one case (11.1%). Lesion margins were smooth
      in five patients (55.6%), irregular in three (33.3%) and spiculated in one
      (11.1%). Pleural retraction or vascular convergence was present in two patients
      (22.2%). Lesions measured 4.8 mm to 25.5 mm (mean, 11.5 mm) and had attenuations
      ranging from -151 to -699 HU (mean, -514.7 HU). Eight (88.9%) manifested as pure
      nodular GGOs and one as mixed GGO with a spiculated margin. In all patients, no
      lesion changes were observed in follow-up CT scans. Focal interstitial fibrosis
      manifesting as nodular GGO usually presents as a solitary nodule with pure GGO on
      thin-section CT, which does not change significantly during follow-up.

PMID- 17429643
TI  - Diagnostic ability of apparent diffusion coefficients for lymphomas and
      carcinomas in the pharynx.
AB  - We evaluated the diagnostic ability of diffusion-weighted imaging for the
      differentiation between lymphomas and carcinomas in the pharynx and between
      carcinomas with different histological types in the pharynx. T1-weighted, fat
      suppressed T2-weighted, and diffusion-weighted MR imaging was performed on 14
      patients with pharyngeal lymphomas, 26 patients with carcinomas of the pharynx, 5
      patients with adenoidal hypertrophy, and 22 patients with normal tonsils.
      Apparent diffusion coefficients (ADCs) were determined by using two b factors
      (500 and 1,000 s/mm(2)). The ADCs of lymphomas were significantly smaller (0.454
      +/- 0.075 x 10(-3) mm(2)/s) than those of carcinomas (0.863 +/- 0.238 x 10(-3)
      mm(2)/s). The ADCs of poorly differentiated and undifferentiated carcinomas
      (0.691 +/- 0.149 x 10(-3) mm(2)/s) were significantly smaller than those of
      moderately differentiated and well-differentiated carcinomas (0.971 +/- 0.221 x
      10(-3) mm(2)/s), but were significantly larger than those of lymphomas. When an
      ADC smaller than 0.560 x 10(-3) mm(2)/s was used for predicting lymphomas, we
      obtained the highest accuracy of 96%, with 100% sensitivity and 94% specificity,
      86% positive predictive value, and 100% negative predictive value. Therefore, ADC
      measurements effectively differentiate lymphomas from carcinomas in the pharynx
      and could be a useful adjunct to biopsy-based development of treatment planning.

PMID- 17429644
TI  - Actual role of radiofrequency ablation of liver metastases.
AB  - The liver is, second only to lymph nodes, the most common site for metastatic
      disease irrespective of the primary tumour. More than 50% of all patients with
      malignant diseases will develop liver metastases with a significant morbidity and
      mortality. Although the surgical resection leads to an improved survival in
      patients with colorectal metastases, only approximately 20% of patients are
      eligible for surgery. Thermal ablation and especially radiofrequency ablation
      emerge as an important additional therapy modality for the treatment of liver
      metastases. RF ablation shows a benefit in life expectancy and may lead in a
      selected patient group to cure. Percutaneous RF ablation appears safer (versus
      cryotherapy), easier (versus laser), and more effective (versus ethanol
      instillation and transarterial chemoembolisation) compared with other minimally
      invasive procedures. RF ablation can be performed by a percutaneous,
      laparoscopical or laparotomic approach, and may be potentially combined with
      chemotherapy and surgery. At present ideal candidates have tumours with a maximum
      diameter less than 3.5 cm. An untreatable primary tumour or a systemic disease
      represents contraindications for performing local therapies. Permanent technical
      improvements of thermal ablation devices and a better integration of thermal
      ablation in the overall patient care may lead to prognosis improvement in
      patients with liver metastases.

PMID- 17429645
TI  - Digital mammography: what do we and what don't we know?
AB  - High-quality full-field digital mammography has been available now for several
      years and is increasingly used for both diagnostic and screening mammography. A
      number of different detector technologies exist, which all have their specific
      advantages and disadvantages. Diagnostic accuracy of digital mammography has been
      shown to be at least equivalent to film-screen mammography in a general screening
      population. Digital mammography is superior to screen-film mammography in younger
      women with dense breasts due to its ability to selectively optimize contrast in
      areas of dense parenchyma. This advantage is especially important in women with a
      genetic predisposition for breast cancer, where intensified early detection
      programs may have to start from 25 to 30 years of age. Tailored image processing
      and computer-aided diagnosis hold the potential to further improve the early
      detection of breast cancer. However, at present no consensus exists among
      radiologists on which processing is optimal for digital mammograms. Image
      processing may also vary significantly among vendors with so far limited
      interoperability. This review aims to summarize the available information
      regarding the impact of digital mammography on workflow and breast cancer
      diagnosis.

PMID- 17429646
TI  - Computer-aided detection in CT colonography: initial clinical experience using a
      prototype system.
AB  - Computer-aided detection (CAD) algorithms help to detect colonic polyps at CT
      colonography (CTC). The purpose of this study was to evaluate the accuracy of CAD
      versus an expert reader in CTC. One hundred forty individuals (67 men, 73 women;
      mean age, 59 years) underwent screening 64-MDCT colonography after full cathartic
      bowel cleansing without fecal tagging. One expert reader interpreted supine and
      prone scans using a 3D workstation with integrated CAD used as "second reader."
      The system's sensitivity for the detection of polyps, the number of false
      positive findings, and its running time were evaluated. Polyps were classified as
      small (< or =5 mm), medium (6-9 mm), and large (> or =10 mm). A total of 118
      polyps (small, 85; medium, 19; large, 14) were found in 56 patients. CAD detected
      72 polyps (61%) with an average of 2.2 false-positives. Sensitivity was 51%
      (43/85) for small, 90% (17/19) for medium, and 86% (12/14) for large polyps. For
      all polyps, per-patient sensitivity was 89% (50/56) for the radiologist and 73%
      (41/56) for CAD. For large and medium polyps, per-patient sensitivity was 100%
      for the radiologist, and 96% for CAD. In conclusion, CAD shows high sensitivity
      in the detection of clinically significant polyps with acceptable false-positive
      rates.

PMID- 17429647
TI  - Measurement by multidetector CT scan of the volume of hypopharyngeal and
      laryngeal tumours: accuracy and reproducibility.
AB  - The purpose of this study was to register the accuracy and reproducibility of the
      multidetector computed tomography (MDCT) estimate of hypopharyngeal and laryngeal
      tumor volumes. Eighteen consecutive patients with larynx or hypopharynx squamous
      cell carcinoma were enrolled in this prospective trial, scheduled for surgery and
      examined by MDCT. A total of 72 tumor volume measurements were reported by two
      different operators, one of them in three different sessions, using the sum-of
      areas method. The results were compared with the volume calculated by surgical
      sampling. The mean tumor volume measured by MDCT was 5.7 +/- 9.3 ml (range 0.1
      41.6). The mean volume measured from the surgical specimens was 5.6 +/- 8.6 ml
      (range 0.06-33.6). The level of agreement between histological and MDCT volumes
      was high, with a slight tendency of MDCT to overestimation, proportional to the
      size. The analysis of interoperator variability showed a tendency of the more
      expert operator to make more accurate estimates, but the differences were not
      significant (P = 0.62, 0.75 and 0.63). The evaluation of the three different
      sessions of the less expert operator revealed a good repeatability. According to
      our study, MDCT estimate of tumor volume is an effective, reproducible method.
      MDCT tends to produce more dispersed results in case of large tumors.

PMID- 17429648
TI  - A new approach to the assessment of lumen visibility of coronary artery stent at
      various heart rates using 64-slice MDCT.
AB  - Coronary artery stent lumen visibility was assessed as a function of cardiac
      movement and temporal resolution with an automated objective method using an
      anthropomorphic moving heart phantom. Nine different coronary stents filled with
      contrast fluid and surrounded by fat were scanned using 64-slice multi-detector
      computed tomography (MDCT) at 50-100 beats/min with the moving heart phantom.
      Image quality was assessed by measuring in-stent CT attenuation and by a
      dedicated tool in the longitudinal and axial plane. Images were scored by CT
      attenuation and lumen visibility and compared with theoretical scoring to analyse
      the effect of multi-segment reconstruction (MSR). An average increase in CT
      attenuation of 144 +/- 59 HU and average diminished lumen visibility of 29 +/-
      12% was observed at higher heart rates in both planes. A negative correlation
      between image quality and heart rate was non-significant for the majority of
      measurements (P > 0.06). No improvement of image quality was observed in using
      MSR. In conclusion, in-stent CT attenuation increases and lumen visibility
      decreases at increasing heart rate. Results obtained with the automated tool show
      similar behaviour compared with attenuation measurements. Cardiac movement during
      data acquisition causes approximately twice as much blurring compared with the
      influence of temporal resolution on image quality.

PMID- 17429649
TI  - Multidetector CT urography: experimental analysis of radiation dose reduction in
      an animal model.
AB  - The purpose of this study was to evaluate the possibility of reducing X-ray
      exposure during multidetector CT urography (MDCTU) considering image quality
      using a porcine model. MDCTU was performed in eight healthy pigs. Scanning was
      conducted using a gradual reduction of the tube current-time product at 120 kV
      [200-20 mAs (eff.) in ten steps]. Three blinded observers independently evaluated
      the image data for anatomic detail, subjective image quality, and subjective
      image noise. Overall image quality was compared to milliampere-second settings
      and radiation dose. Objective noise measurements were assessed. Noise
      measurements in patients were also performed to verify the comparabilty of the
      animal model. Adequate image quality allowing for detailed visualization of the
      upper urinary tract was obtained when the tube current-time product was decreased
      to 70 eff. mAs at 120 kV. Image noise did not impair image quality to a relevant
      degree using these parameters. There was high agreement among the observers (ICC
      = 0.95). In the animal experiments, reduced-dose MDCTU produced good image
      quality. A maximum current-time product reduction to 70 eff. mAs at 120 kV
      (CTDI(vol) = 5.3 mGy) proved to be feasible, thereby offering an advantageous
      dosage reduction. The study provides a basis for the development of reduced-dose
      MDCTU protocols in humans.

PMID- 17429650
TI  - High-resolution myocardial perfusion imaging at 3 T: comparison to 1.5 T in
      healthy volunteers.
AB  - The purpose of this study was to evaluate high-resolution (HR) myocardial first
      pass perfusion in healthy volunteers at 3 T compared to a typical clinical
      imaging protocol at 1.5 T, with respect to overall image quality and the presence
      of subendocardial dark rim artifacts. Myocardial first-pass rest perfusion
      studies were performed at both field strengths using a T1-weighted saturation
      recovery segmented k-space gradient-echo sequence combined with parallel imaging
      (Gd-DTPA 0.05 mmol/kg). Twenty-six healthy volunteers underwent (1) a HR
      perfusion scan at 3 T(pixel size 3.78 mm(2)) and (2) a standard perfusion
      approach at 1.5 T(pixel size 9.86 mm(2)). The contrast enhancement ratio (CER)
      and overall image quality (4-point grading scale: 4: excellent; 1: non
      diagnostic) were assessed, and a semiquantitative analysis of dark rim artifacts
      was performed for all studies. CER was slightly higher (1.31 +/- 0.32 vs. 1.14 +/
      0.34; p<0.01), overall image quality was significantly improved (3.03 +/- 0.43
      vs. 2.37 +/- 0.39; p<0.01), and the number of dark rim artifacts (139 +/- 2.09
      vs. 243 +/- 2.33; p<0.01) was significantly reduced for HR perfusion imaging at 3
      T compared to the standard approach at 1.5 T. HR myocardial rest perfusion at 3 T
      is superior to the typical clinical perfusion protocol performed at 1.5 T with
      respect to the overall image quality and presence of subendocardial dark rim
      artifacts.

PMID- 17429651
TI  - Asymptomatic spontaneous acute vertebral artery dissection: diagnosis by high
      resolution magnetic resonance images with a dedicated surface coil.

PMID- 17429652
TI  - [Subjective and objective outcome following implantation of the apodized
      diffractive AcrySof ReSTOR].
AB  - BACKGROUND: Our purpose in this study was to assess the postoperative subjective
      and objective results after implantation of the Acrysof ReSTOR lens and to
      evaluate the advantages and limitations of the apodized diffractive optic design
      of this new multifocal intraocular lens (MIOL). METHODS: Phakoemulsification and
      implantation of an Acrysof ReSTOR was performed in 55 eyes of 32 patients. All
      patients were examined after a mean period of 7.9+/-1.9 months. The accuracy of
      lens calculation was evaluated for the Haigis, Holladay I, and SRK-T formulas.
      Uncorrected and corrected visual acuity for distance and for intermediate and
      near vision were assessed, as was stereoacuity. In addition, contrast sensitivity
      was tested under photopic and mesopic conditions, with and without glare. The
      patients were asked about dysphotic phenomena such as halos, glare or flare, and
      night vision using a standardized evaluation. The degree to which patients were
      able to manage without spectacles after the surgery was also documented. RESULTS:
      The median monocular uncorrected visual acuity (UCVA) for distance was 20/25
      (LogMAR 0.05) while the binocular UCVA was 20/20 (LogMAR 0). The monocular
      uncorrected acuity for near vision was 20/25 (LogMAR 0.1), the binocular near
      visual acuitiy was 20/20 (LogMAR 0), while the intermediate monocular visual
      acuity was 20/50 (LogMAR 0.4) and the binocular, 20/32 (LogMAR 0.2). Contrast
      sensitivity was within the normal range. Dysphotic phenomena were noted by 66% of
      patients but were so slight as not to cause any problem at all in 59%. For close
      work and distance vision 84% of all patients needed no correcting glasses, while
      78% did not need to use glasses for intermediate vision. CONCLUSION: The Acrysof
      ReSTOR provides excellent uncorrected visual acuity for distance and near vision
      and the level of patient satisfaction achieved with it is good.

PMID- 17429653
TI  - Absorption of short-chain fatty acids, sodium and water from the forestomach of
      camels.
AB  - In camelids the ventral parts of compartments 1 and 2 (C1/C2) and the total
      surface of compartment 3 of the forestomach are lined with tubular glands,
      whereas in ruminants the surface of the forestomach is composed entirely of
      stratified, squamous epithelium. Thus, differences in absorption rates between
      these foregut fermenters can be expected. In five camels C1/C2 was temporarily
      isolated, washed and filled with buffer solutions. Absorption of short-chain
      fatty acids (SCFA) and net absorption of sodium and water were estimated relative
      to Cr-ethylenediaminetetraacetic acid as a fluid marker. SCFA were extensively
      absorbed in the forestomach; clearance rates of SCFA with different chain lengths
      were equal. After lowering the pH of solutions SCFA absorption rates increased,
      but much less than the increase of the non-ionized fraction. Absorption of
      propionate was lower when acetate had been added. Findings suggest that most of
      the SCFA in camels are transported in the ionized form, most likely via an anion
      exchange mechanism. Net water absorption is closely related to net sodium
      absorption. Apparently water absorption results from an iso-osmotic process.
      Differences between absorption mechanisms of SCFA from the forestomach of
      camelids and ruminants are discussed.

PMID- 17429654
TI  - Central ventilatory control in the South American lungfish, Lepidosiren paradoxa:
      contributions of pH and CO(2).
AB  - Lungfish represent a probable sister group to the land vertebrates. Lungfish and
      tetrapods share features of respiratory control, including central, peripheral
      and intrapulmonary CO(2) receptors. We investigated whether or not central
      chemoreceptors in the lungfish, L. paradoxa, are stimulated by CO(2) and/or pH.
      Ventilation was measured by pneumotachography for diving animals. The fourth
      cerebral ventricle was equipped with two catheters for superfusion. Initially,
      two control groups were compared: (1) catheterized animals with no superfusion
      and (2) animals superfused with mock CSF solutions at pH = 7.45; PCO(2) = 21
      mmHg. The two groups had virtually the same ventilation of about 40 ml BTPS kg(
      1) h(-1) (P > 0.05). Next, PCO(2) was increased from 21 to 42 mmHg, while pH(CSF)
      was kept at 7.45, which increased ventilation from 40 to 75 ml BTPS kg(-1) h(-1).
      Conversely, a decrease of pH(CSF) from 7.45 to 7.20 (PCO(2) = 21 mmHg) increased
      ventilation to 111 ml BTPS kg(-1) h(-1). Further decreases of pH(CSF) had little
      effect on ventilation, and the combination of pH(CSF) = 7.10 and PCO(2) = 42 mmHg
      reduced ventilation to 63 ml BTPS kg(-1) h(-1).

PMID- 17429655
TI  - Change in cerebral autoregulation as a function of time in children after severe
      traumatic brain injury: a case series.
AB  - OBJECTIVE: The objective of this study was to describe changes in cerebral
      autoregulation after severe pediatric traumatic brain injury (TBI). MATERIALS AND
      METHODS: Two cerebral autoregulation tests were performed during the first 10
      days after severe TBI in children <16 years. Cerebral autoregulation was
      quantified using the mean autoregulatory index (mARI). RESULTS: Nine (five
      males/four females) children (10 +/- 5 years) with severe (admission Glasgow Coma
      Scale (GCS), 5 +/- 2) TBI were enrolled. Thirty (3/9) percent of initial exams
      revealed impaired cerebral autoregulation; all three had returned to intact
      cerebral autoregulation on second exam. However, in three of nine (33%) patients,
      cerebral autoregulation worsened on second exam. Of the factors examined,
      worsening mARI on second exam was associated with worsening head computed
      tomography (CT) lesion. CONCLUSIONS: Cerebral autoregulation often changed and
      worsened during the first 9 days after severe pediatric TBI. Worsening cerebral
      autoregulation may mirror worsening TBI.

PMID- 17429656
TI  - Spatial perception predicts laparoscopic skills on virtual reality laparoscopy
      simulator.
AB  - OBJECTS: This study evaluates the influence of visual-spatial perception on
      laparoscopic performance of novices with a virtual reality simulator (LapSim(R)).
      MATERIALS AND METHODS: Twenty-four novices completed standardized tests of visual
      spatial perception (Lameris Toegepaste Natuurwetenschappelijk Onderzoek [TNO]
      Test(R) and Stumpf-Fay Cube Perspectives Test(R)) and laparoscopic skills were
      assessed objectively, while performing 1-h practice sessions on the LapSim(R),
      comprising of coordination, cutting, and clip application tasks. Outcome
      variables included time to complete the tasks, economy of motion as well as total
      error scores, respectively. RESULTS: The degree of visual-spatial perception
      correlated significantly with laparoscopic performance on the LapSim(R) scores.
      Participants with a high degree of spatial perception (Group A) performed the
      tasks faster than those (Group B) who had a low degree of spatial perception (p =
      0.001). Individuals with a high degree of spatial perception also scored better
      for economy of motion (p = 0.021), tissue damage (p = 0.009), and total error (p
      = 0.007). CONCLUSION: Among novices, visual-spatial perception is associated with
      manual skills performed on a virtual reality simulator. This result may be
      important for educators to develop adequate training programs that can be
      individually adapted.

PMID- 17429657
TI  - Hydrocephalus in children born in 1999-2002: epidemiology, outcome and
      ophthalmological findings.
AB  - OBJECTIVE: The purpose of this study was to monitor incidence and outcome in
      children with hydrocephalus. MATERIALS AND METHODS: This is a population-based
      prospective study of all the children with hydrocephalus born in western Sweden
      in 1999-2002. Etiological and clinical information was collected from records,
      neuroimaging and ophthalmological examinations. Comparisons with 208 children
      born in 1989-1998 were made. RESULTS: The incidence was 0.66 per 1,000 live
      births, 0.48 for infantile hydrocephalus and 0.18 for hydrocephalus associated
      with myelomeningocele. The corresponding rates for 1989-1998 were 0.82, 0.49 and
      0.33. Ventriculo-peritoneal shunt treatment was used in 42 of the 54 children and
      endoscopic third ventriculostomy in 12. Revisions were performed in 33 (61%).
      Neurological impairments were present in 63%, and they were more common in
      children born preterm than in those born at term. The radiological extent of
      parenchymal lesions correlated significantly with outcome. Ophthalmological
      abnormalities were found in 80%, including visual impairment in one third.
      CONCLUSION: The incidence of post-haemorrhagic hydrocephalus in children born
      extremely preterm increased; a group running a high risk of neurological
      sequelae. Ophthalmological abnormalities were frequent and need to be assessed in
      all children with hydrocephalus. The high rate of morbidity and complications
      necessitates the further development of preventive and treatment methods.

PMID- 17429658
TI  - Posterior fossa tumors in children: how long does it take to establish the
      diagnosis?
AB  - OBJECTIVE: The aim of this study is to evaluate, for our patient population, the
      time interval from the first chart-documented symptom to the radiological
      diagnosis in children and infants with posterior fossa tumors. MATERIALS AND
      METHODS: We retrospectively analyzed 50 consecutive children (36 men, 14 women)
      with posterior fossa tumor treated at our department between January 1999 and
      December 2003. The mean age at time of diagnosis was 98 months (6 months-16
      years). The mean follow up was 27 months (6-61 months). The diagnoses included
      astrocytoma (n = 17), medulloblastoma (n = 15), ependymoma (n = 6), and other
      tumors (n = 12). RESULTS: The mean time interval between onset of symptoms and
      radiographic diagnosis was 142 days (5-535 days), the median was 59 days. The
      mean time for Grade I and II tumors was 238 days (n = 19) and for tumors Grade
      III and IV 117 days (n = 31). The most common presenting symptoms were headache,
      nausea, vomiting, ataxia, and oculomotor deficits. Approximately half of the
      patients were initially diagnosed and treated for other diseases
      (gastrointestinal infection, appendicitis, psychological behavioral problems,
      cervical spine strains, different ophthalmologic entities). Specialists
      (ophthalmologists, orthopedics) tended to diagnose and treat their specific
      diagnoses (e.g., strabism, torticollis). Parents play a significant role in the
      process of establishing the correct diagnosis. CONCLUSION: We conclude that
      further information and education regarding symptomatology and diagnosis of
      posterior fossa tumors in children is necessary. Communication has to be improved
      between parents and referring physicians of all specialties and neurosurgeons.

PMID- 17429659
TI  - An unusual cause of salivary leak post tracheoesophageal fistula repair.
AB  - LB was a male infant born via spontaneous vaginal delivery at term in a
      peripheral centre. A provisional diagnosis of oesophageal atresia (OA) with
      tracheoesophageal fistula (TOF) was made and the child was transferred to a
      tertiary centre for further evaluation. On day two of life he underwent repair of
      his oesophageal atresia and division of his distal tracheoesophageal fistula. The
      upper and lower oesophageal segments were brought together with average tension.
      An extrapleural drain was inserted with the tip sutured close to the anastomosis.
      His post-operative course was complicated by two failed extubations secondary to
      respiratory distress and the development of a salivary leak. Despite
      repositioning of the extrapleural drain on two separate occasions, the salivary
      leak continued. Day 25 post-operatively he underwent direct laryngoscopy,
      bronchoscopy and oesophagoscopy. The extrapleural drain was found to be causing
      tracheal compression and the tip of the drain was located within the lumen of the
      oesophagus. Saliva leak is not an uncommon complication of this oesophageal
      atresia repair. This is the first report of an extrapleural drain being found in
      the oesophagus causing salivary leak and tracheal compression. These
      complications may have been prevented by ensuring the drain did not impinge on
      the anastomosis site, by pulling the drain back at an earlier time or by not
      having used an extrapleural drain at all.

PMID- 17429661
TI  - [Laboratory diagnostics of systemic autoimmune diseases. Part II: rheumatoid
      arthritis and vasculopathies].
AB  - This is the second part in a series of articles on the laboratory diagnostics of
      rheumatic diseases. It addresses rheumatoid arthritis, systemic, anti-neutrophil
      cytoplasmatic antibody (ANCA) positive vasculitides and antiphospholipid
      syndrome. The diagnostics of rheumatoid arthritis has been substantially improved
      by the recently introduced assay for antibodies against citrullinated peptides.
      In addition, a number of vasculitides can be differentiated by the presence of
      ANCA. Beta2-glycoprotein I antibodies and lupus anticoagulants are at present the
      most specific markers for antiphospholipid syndrome. Inflammatory activity can be
      monitored by determining the levels of acute phase proteins and erythrocyte
      sedimentation rate, but only in some situations by measuring immunoglobulins and
      interleukins.

PMID- 17429660
TI  - Signalling molecules: clues from development of the limb bud for cryptorchidism?
AB  - Recent studies of testicular descent suggest not only that the gubernaculum does
      not initially attach to the scrotum, but also that it must migrate from the
      groin. Two findings suggest that the gubernaculum may behave like an embryonic
      limb bud during this phase. First, the active growth centre is at the distal tip
      of the gubernaculum. Secondly, the gubernaculum is loose in the subcutaneous
      tissues beneath Scarpa's fascia. The free protrusion of the gubernaculum from the
      abdominal wall was so reminiscent of a developing embryonic limb bud, we thought
      that the biological controls of both processus may be similar. This review
      examines what is known about vertebrate limb bud development, and compares the
      mechanisms to what has recently been discovered in the gubernaculum. The
      hypothesis that both processes may be similar is initially consistent with the
      current facts, encouraging us to investigate this further experimentally.

PMID- 17429662
TI  - [The mechanism of bone loss in rheumatoid arthritis. Description based on a case
      report].
AB  - Various factors influencing bone turnover and bone loss in rheumatoid arthritis
      (RA) are illustrated using the example of a postmenopausal woman with a highly
      active RA. In particular, the relationships between disease activity, vitamin D
      metabolism, parathyroid hormone (PTH) levels and calcium metabolism are
      described. High disease activity is associated with low levels of 25
      hydroxycholecalciferol, and especially of 1.25-dihydroxycholecalciferol. Despite
      vitamin D deficiency, PTH levels were decreased and histomorphometric
      investigation of the iliac crest biopsy showed severe osteoporosis but no signs
      of osteomalacia. Suppression of the inflammatory disease activity of RA led to a
      normalisation of the serum levels of 1.25-dihydroxycholecalciferol and PTH. This
      was associated with a reduction in the initially increased levels of bone
      specific alkaline phosphatase to normal values. This case report shows a close
      relationship between disease activity and bone turnover in RA and indicates that
      early investigation and therapy of disturbances of bone metabolism in RA are
      necessary.

PMID- 17429663
TI  - Malignant glioneuronal tumor of the adult cerebrum with neuropil-like islands
      involving "proliferating nodules": confirmatory report of an unusual variant.

PMID- 17429664
TI  - Endoscopic resection of the gouty tophi of the first metatarsophalangeal joint.
AB  - Gouty tophus of the first metatarsophalangeal joint can cause shoewear problem.
      It can ulcerate and lead to secondary infections. Wound complications are common
      after open resection of the tophus. We describe an endoscopic approach to resect
      the tophus in order to minimize the soft tissue complications.

PMID- 17429665
TI  - Synovial knee affected in multiple hemangiomatosis.
AB  - Synovial hemangioma is a vascular lesion of joint cavities. It is a rare cause of
      pain and spontaneous hemarthrosis in the paediatric age group. It is often seen
      as an internal derangement of the knee. We present the case of a 37-year-old
      woman with a history of recurrent effusions of this joint. The MRI showed a soft
      tissue mass affecting the Hoffa's fat pad and the synovial surrounding the
      patella. Other hemangiomas were detected in other sides of the body. Through
      arthroscopy, we eliminated all the pathological tissue of the knee. The patient
      remains asymptomatic after 1 year.

PMID- 17429666
TI  - Isolated fetal intracardiac hyperechogenic focus associated with neonatal outcome
      and triple test results.
AB  - OBJECTIVE: To investigate the relationship between isolated intracardiac
      hyperechogenic focus (IHF) in the mid trimester of pregnancy with neonatal
      outcomes and triple test results. MATERIALS AND METHODS: The study included low
      risk pregnant women who came for routine follow-up to our antenatal clinic
      between years 2000 and 2005. A detailed structural survey by ultrasound (USG) of
      the fetal heart was performed on each fetus in the mid-trimester of pregnancy.
      All patients had mid-trimester triple tests performed between the 16th and 18th
      weeks' of pregnancy. We recruited a total of 40 pregnancies that had fetal IHF in
      the level II USG examination and a control group of 100 healthy pregnant women
      those which were followed-up during the same period. Twenty-nine fetuses (72.5%)
      had left, 8 (20%) had right whereas 3 (7.5%) had bilateral ventricular IHF. We
      compared the perinatal and neonatal outcomes and triple test results of the
      fetuses that had right and left IHF, and the controls. RESULTS: Cytogenetic
      amniocentesis was performed to 6 (15%) women in the study and 5 (5%) in the
      control group and all were normal. During follow-up IHF spontaneously disappeared
      in 30 fetuses [right (n: 5), left (n: 23) or bilateral (n: 2)]. We did not
      observe any cardiac problem in the postnatal period in all newborns. Only one
      infant (2.5%) in the study group was admitted to neonatal intensive care unit
      because of prematurity. Median delivery weeks (P = 0.023), head circumference (P
      = 0.013), 5-min Apgar score (P = 0.021] and apnea (P = 0.042) were significantly
      higher in fetuses with right IHF. Compared to the controls, median delivery weeks
      (P = 0.038) was significantly higher in fetuses with right IHF, but head
      circumference (P = 0.004), 1-min (P = 0.003) and 5-min (P < 0.001) Apgar scores
      were lower in fetuses with left IHF. However no difference was observed in second
      trimester serum human chorionic gonadotropin (HCG), alpha-fetoprotein (AFP) and
      estriol (E(3)) levels, in the three groups. There was no correlation between
      serum HCG, AFP and E(3) levels and the presence of IHF. CONCLUSIONS: Isolated IHF
      in the fetal heart in the mid-trimester of pregnancy seems not associated with
      adverse neonatal outcome and does not correlate with triple test results.

PMID- 17429667
TI  - Cystic hygroma and lymphangioma: associated findings, perinatal outcome and
      prognostic factors in live-born infants.
AB  - OBJECTIVES: We aimed to determine associated ultrasonographic findings,
      chromosome abnormalities and the prognostic factors of cystic hygromas in live
      born infants. METHODS: We reported a series of 57 cystic hygroma cases, who were
      diagnosed in the first and the second trimester of pregnancy by means of the
      ultrasonographic morphology of cystic hygroma, associated structural
      abnormalities, karyotype analysis and the autopsy findings. Survivors were
      followed for their fetal outcome and prognosis. RESULTS: There were 57 new cases
      of cystic hygroma among 8,155 screenings (0.7%). 35 of the cases (61.4%) were
      nonseptated and 22 of the cases (38.6%) were septated cystic hygroma. Chromosomal
      abnormalities were found in 23 of the cases (40.3%). The most common abnormality
      in nonseptated cystic hygroma was trisomy 21 (8 cases, 25%) and in septated
      cystic hygroma was Turner syndrome (4 cases, 21.1%). The most common associated
      structural malformations were cardiac abnormalities (in 7 cases, 20%) in
      nonseptated cystic hygroma cases and nonimmune hydrops (in 12 cases, 54.5%) in
      septated cystic hygroma cases. Overall survival was poor; only one case of
      septated cystic hygroma with axillary location and seven cases of nonseptated
      cystic hygroma, of whom two died in the neonatal period, were alive (10.5%). This
      study had 80% power to detect 0.03% difference in diagnosis cystic hygroma (alpha
      = 0.05, beta = 0.80). CONCLUSION: Fetuses with cystic hygroma are at high risk
      for adverse outcome. Prenatal diagnosis with invasive procedures should be done
      in order to inform the parents in detail. Axillary location of the hygroma and
      the depth of invasion had prognostic importance.

PMID- 17429668
TI  - Prevalence of pathology in women attending colposcopy for postcoital bleeding
      with negative cytology.
AB  - OBJECTIVE: To determine the frequency of cervical pathology and the incidence of
      cervical neoplasia in women presenting with PCB at the colposcopy clinic with
      negative cytology. DESIGN: A retrospective study. SETTING: A district general
      hospital. POPULATION: Eighty-seven women with postcoital bleeding and negative
      cytology were seen in the colposcopy unit during 1 January 2003 to 31 December
      2005. METHODS: Women were identified from computer records and details were
      extracted from the case notes. MAIN OUTCOME MEASURE: Histopathological diagnosis.
      RESULTS: Six women (6.9%) had cervical intraepithelial neoplasia. There were no
      cases of invasive cancer. Thus in our study 6.9% women with postcoital bleeding
      had abnormal histology even though they had normal smears. Other identifiable
      causes were cervical polyp (12.5%), ectopy (33.6%) and Chlamydia (2.3%). No
      pathology was found in 50% of women. CONCLUSION: Women with postcoital bleeding
      even with normal smears appear to be at much greater risk of cervical neoplasia
      than the general population. Unfortunately there is no general consensus for
      management of these patients. Hence further research is needed to standardise the
      management of women with PCB. Patients should be reassured that in vast majority
      of cases no serious pathology is detected.

PMID- 17429669
TI  - Spontaneous preterm delivery and gestational diabetes: the impact of glycemic
      control.
AB  - OBJECTIVE: Opinions differ whether the rate of spontaneous preterm delivery
      (sPTD) increases in pregnancies complicated with GDM. We sought to characterize,
      which factors may influence the rate of sPTD in GDM. METHODS: We conducted a
      retrospective study with 1,526 GDM patients, all treated at the same center by
      the same diabetic protocol using self-blood glucose monitoring. The rate of sPTD
      was compared to that of 10,560 non-diabetic women. Eligibility for the study was
      limited to women with a singleton pregnancy with spontaneous onset of delivery
      before 37 weeks of gestation with no history of chronic maternal illness, i.e.,
      chronic hypertension or development of preeclampsia in the current pregnancy, and
      no clear indication for preterm delivery. Mean blood glucose < 105 mg dl(-1) was
      defined as well controlled. RESULTS: Overall, no difference was found in the rate
      of sPTD in GDM (163/1,526, 10.7%) in comparison to non-GDM patients (1193/10,560,
      11.3%, P = 0.2). In the GDM group, a comparison between women with and without
      sPTD found no difference in maternal age (28.1 +/- 6 vs. 28.2 +/- 6),
      prepregnancy BMI (28.1 +/- 5 vs. 27.8 +/- 6), rate of nulliparity (38 vs. 34%) or
      ethnicity origin. GDM patients with sPTD were characterized by higher glucose
      values in the OGTT and higher mean blood glucose (114 +/- 16 vs. 106 +/- 14, P <
      0.0001). Sixty-five percent of patients with sPTD versus. 46% in the non-sPTD
      were in poor glycemic control (P = 0.004). Multiple logistic regressions, when
      the dependent variable was sPTD revealed that mean blood glucose (OR 1.94 95% CI
      1.25-3.0), history of sPTD (OR 3.25 95% CI 2.1-4.8) and parity (OR 1.49 95% CI
      1.05-2.2) were contributing factors. CONCLUSION: The rate of sPTD in GDM is not
      increased in comparison to non-GDM patients, but reaching established levels of
      glycemic control may reduce the rate of sPTD in GDM.

PMID- 17429670
TI  - Acute abdomen with bones in the spleen.
AB  - INTRODUCTION: A 28-year old female presented with a non-radiating persistent left
      upper quadrant pain and tenderness for 5 weeks. METHODS: A preliminary CT scan
      displayed bony structures in the spleen. A delayed scanning subsequently showed
      the bones to have changed position, consistent with a life fetus. RESULTS:
      Ultrasound confirmed the CT findings, and ascertained the fetus to be consistent
      with 13 weeks of gestation. Laparoscopic splenectomy was performed and
      examination of the intact spleen confirmed a male fetus that was morphologically
      normal. CONCLUSION: This is the first report of fetal bony structures in the
      spleen associated with an advanced intra-splenic pregnancy.

PMID- 17429671
TI  - Detection of UV-induced activation of NF-kappaB in a recombinant human cell line
      by means of Enhanced Green Fluorescent Protein (EGFP).
AB  - The cellular protection reaction known as ultraviolet (UV) response leads to
      increased transcription of several genes. Parts of this transcriptional response
      are transmitted via activation of the Nuclear factor kappaB (NF-kappaB). The
      contribution of different UV radiation qualities to this process is not yet
      known. In a previous work, a stably transfected human cell line was developed
      which indicates activation of the NF-kappaB pathway by fluorescence of the
      reporters Enhanced Green Fluorescent Protein (EGFP) and its destabilized variant
      (d2EGFP) thereby allowing a fast and reliable monitoring of UV effects on the NF
      kappaB pathway. Cells were exposed to a mercury low-pressure lamp or to simulated
      sunlight of different wavelength ranges and subjected to flow cytometric analysis
      after different post-irradiation periods. Growth capacity of cells after UV
      irradiation was quantified using a luminance measurement of crystal violet
      stained cell layers. In contrast to UVC and UVB, UVA radiation induced d2EGFP
      expression and NF-kappaB activation in a non-cytotoxic dose range. These results
      show that NF-kappaB plays a role in the UVA-induced gene activation in a non
      cytotoxic dose range in a human epithelial cell line.

PMID- 17429672
TI  - Monte Carlo-based calculation of imaging plate response to (90)Sr in teeth:
      experimental validation of the required correction on sample thickness.
AB  - Recently, a numerical method was proposed to correct the imaging plate (IP)
      response to (90)Sr concentration in tooth samples, depending on the sample
      thickness. This is important to quantify any (90)Sr concentration in teeth, which
      in turn is necessary to determine any (90)Sr incorporation of a person
      retrospectively. Although the final goal will be to evaluate the (inhomogeneous)
      spatial distribution of (90)Sr inside tooth samples precisely, the present study
      was restricted -- as a first step -- to the evaluation of (90)Sr in teeth
      assuming a uniform (90)Sr distribution. A numerical method proposed earlier was
      validated experimentally in the present study by measuring the IP response to
      standard sources of various thicknesses and (90)Sr concentrations. For
      comparison, the energy deposition of the beta-rays emitted by (90)Sr in the IP --
      which is considered to be proportional to the IP luminescence signal -- was
      calculated for the various sample thicknesses involved, by means of the MCNP-4C
      code. As a result, the measured IP response could be reproduced by the
      calculations within the uncertainties, depending on the thickness of the standard
      sources. Thus, the validity of the proposed numerical method to correct the IP
      response for sample thickness has successfully been demonstrated.

PMID- 17429673
TI  - Photodynamic therapy for recurrent hyphema after proton beam radiotherapy of iris
      melanoma.
AB  - BACKGROUND: Recurrent hemorrhage with secondary glaucoma is a rare but serious
      complication following proton beam irradiation (PBI) of iris melanoma. We report
      a case in which photodynamic therapy (PDT) was successfully used to treat this
      complication. METHODS: The history, clinical features and management of a patient
      with iris melanoma who was treated with PBI and later developed recurrent hyphema
      and increased intraocular pressure are presented. PDT was used to treat the
      abnormal intralesional blood vessels which caused the recurrent intraocular
      haemorrhage. RESULTS: The intralesional blood vessels regressed following PDT.
      The patient did not experience any further episodes of hyphema or elevated
      intraocular pressure. CONCLUSIONS: Our case demonstrates that the vascular
      abnormalities following irradiation of iris melanoma may respond favorably to PDT
      in selected cases. To our knowledge, this is the first reported case in which PDT
      was used to treat recurrent hyphema caused by abnormal intralesional blood
      vessels after proton beam irradiation of iris melanoma.

PMID- 17429674
TI  - Combined grading for choroidal neovascularisation: colour, fluorescein
      angiography and autofluorescence images.
AB  - BACKGROUND: Patients with age-related macular degeneration (ARMD) have several
      imaging techniques carried out regularly. In this study we introduce a new
      grading model of autofluorescence images (AF), compare it with fluorescein
      angiography (FFA) and digital colour fundus photos (COL) and test for inter- and
      intraobserver reliability. METHODS: A total of 71 eyes of 54 patients with
      bilateral or unilateral CNV had COL, FFA and AF, fulfilling the inclusion
      criterion of having all 3 types of imaging carried out on the same day or within
      14 days. The grading of COL was performed by a trained grader based on the
      International ARM classification; FFA and AF images were independently graded by
      two trained retinal specialists in order to assess inter-observer reliability.
      Overall, 30% of all images were regraded after at least 14 days interval to
      assess intra-observer variability. RESULTS: The intergrader agreement was exact
      for classification of CNV (k = 1.00); almost perfect for FFA features (k = 0.83)
      and correspondence of decreased AF to COL (k = 0.94); substantial for patterns of
      decreased and increased AF (k = 0.80, k = 0.78), correspondence of patterns of
      increased AF to FFA and to COL (k = 0.78, k = 0.74) and background AF (k = 0.72);
      moderate for CNV diameter in FFA (k = 0.45), FFA pattern (k = 0.43), dimension of
      increased and decreased AF (k = 0.5, k = 0.56); fair for quality of FFA and AF
      images (k = 0.21, k = 0.26) respectively. The intragrader agreement varied from
      exact to substantial for all categories. Diffuse and reticular patterns of
      decreased AF and reticular pattern of increased AF correlated well, with visual
      acuity worse than 6/24. CONCLUSION: The combined grading system was reliable for
      evaluating the three imaging techniques, and might be suitable for
      epidemiological studies and therapeutic trials where such grading is warranted.
      Certain AF patterns seem to predict VA outcome better than one might have
      predicted based on FFA. Further studies are needed to evaluate its usefulness in
      clinical settings for predicting outcomes for patients receiving therapy for end
      stage disease.

PMID- 17429675
TI  - Odor and chemesthesis from exposures to glutaraldehyde vapor.
AB  - OBJECTIVES: Assessment of olfactory and chemesthetic sensitivity (feel, sensory
      irritation) to vapor of glutaraldehyde in young adult females. For chemesthetic
      sensitivity, assessment included the variable of duration, with focus on whether
      concentrations initially too low to evoke feel in the eye or upper airway might
      do so in exposures up to 15 min. METHODS: Experiment 1 probed sensitivity with
      forced-choice testing of detection over ranges of concentrations appropriate to
      three endpoints: odor, feel in the eye, and feel in the nose. A subject
      participated in hours of testing per endpoint to yield enough data to erect a
      psychometric (concentration-response) function. Exposure in Experiment 1 entailed
      use of a vapor-delivery system that stimulated sites of interest separately.
      Exposure in Experiment 2 occurred in the ambient environment of a chamber, with
      the sites stimulated simultaneously. In that case, subjects rated confidence by
      the minute that they felt the presence of vapor in the eyes, nose, and throat
      during exposures of 15 minutes to 35, 50, 75, and 100 ppb, a blank, and an odor
      control of mild heptane. RESULTS: In Experiment 1, the typical subject achieved
      50% detection (threshold) of odor at 0.3 ppb. The typical subject achieved 50%
      detection of feel in the eye and nose at 390 and 470 ppb, respectively.
      Psychometric functions for feel showed much sharper dependence on concentration
      than those for odor. In Experiment 2, confidence in detection of feel migrated
      progressively away from no-with certainty toward the zone of uncertainty, with
      bigger change when the exposures contained any glutaraldehyde. The ratings of
      confidence failed, however, to show distinguish among these concentrations.
      CONCLUSIONS: Glutaraldehyde has much higher odor potency than previously thought.
      Its green-apple odor should signal presence of the vapor at levels more than a
      100-fold below any that might evoke sensory irritation in brief exposures.
      Exposures that start decidedly below irritating (100 ppb and below) seem unlikely
      to turn irritating over time. Although the effects from these concentrations
      differentiated themselves from those of air and an odor control, they exhibited
      none of the concentration dependence seen for sensations of feel. They seemed
      likely driven by the penetrating odor of glutaraldehyde.

PMID- 17429676
TI  - Brain temperature in endotherms plays a crucial role in the regulation of
      numerous physiological functions.

PMID- 17429677
TI  - Cross-validation of the 20- versus 30-s Wingate anaerobic test.
AB  - The 30-s Wingate anaerobic test (30-WAT) is the most widely accepted protocol for
      measuring anaerobic response, despite documented physical side effects.
      Abbreviation of the 30-WAT without loss of data could enhance subject compliance
      while maintaining test applicability. The intent of this study was to quantify
      the validity of the 20-s Wingate anaerobic test (20-WAT) versus the traditional
      30-WAT. Fifty males (mean +/- SEM; age = 20.5 +/- 0.3 years; Ht = 1.6 +/- 0.01 m;
      Wt = 75.5 +/- 2.6 kg) were randomly selected to either a validation (N = 35) or
      cross-validation group (N = 15) and completed a 20-WAT and 30-WAT in double
      blind, random order on separate days to determine peak power (PP; W kg(-1)), mean
      power (MP; W kg(-1)), and fatigue index (FI; %). Utilizing power outputs
      (relative to body mass) recorded during each second of both protocols, a non
      linear regression equation (Y (20WAT+10 )= 31.4697 e(-0.5)[ln(X
      (second)/1174.3961)/2.6369(2)]; r (2) = 0.97; SEE = 0.56 W kg(-1)) successfully
      predicted (error approximately 10%) the final 10 s of power outputs in the cross
      validation population. There were no significant differences between MP and FI
      between the 20-WAT that included the predicted 10 s of power outputs (20-WAT+10)
      and the 30-WAT. When derived data were subjected to Bland-Altman analyses, the
      majority of plots (93%) fell within the limits of agreement (+/-2SD). Therefore,
      when compared to the 30-WAT, the 20-WAT may be considered a valid alternative
      when used with the predictive non-linear regression equation to derive the final
      power output values.

PMID- 17429678
TI  - Theoretical limits on brain cooling by external head cooling devices.
AB  - Numerous experimental studies have demonstrated that mild hypothermia is a rather
      promising therapy for acute brain injury in neonates. Because measurement of the
      resultant cooling of human brain in vivo is beyond current technology, an
      understanding of physical factors limiting the possible brain cooling would be a
      substantial achievement. Herein brain cooling by external head cooling devices is
      studied within the framework of an analytical model of temperature distribution
      in the brain. Theoretical limits on brain hypothermia induced by such devices are
      established. Analytical expressions are obtained that allow evaluation of changes
      in brain temperature under the influence of measurable input parameters. We show
      that a mild hypothermia can be successfully induced in neonates only if two
      necessary conditions are fulfilled: sufficiently low cerebral blood flow and
      sufficiently high value of the heat transfer coefficient describing the heat
      exchange between the head surface and a cooling device.

PMID- 17429679
TI  - Targeted brain hypothermia induced by an interstitial cooling device in human
      neck: theoretical analyses.
AB  - In this study, the feasibility of a newly developed interstitial cooling device
      inserted into the neck muscle and placed on the surface of the common carotid
      artery is evaluated. A combination of vascular model and continuum model is
      developed to simulate the temperature fields in both the neck and brain regions.
      Parametric studies are conducted to test the sensitivity of various factors on
      the temperature distribution. It has been shown that the length of the device,
      temperature of the device, and the tissue gap between the device and the blood
      vessel are the dominant factors that determine the effectiveness of this cooling
      approach. Under the current design parameters, the device is capable of inducing
      a temperature drop of 2.8 degrees C along the common carotid artery and it
      results in a total of 90 W of heat carried away from the arterial blood. Although
      the degree of the cooling in the arterial blood is inversely proportional to the
      blood flow rate of the arteries, the total heat loss from the arterial blood does
      not vary significantly if the blood flow rate changes during the cooling. After
      the cold arterial blood is supplied to the brain hemisphere, temperature
      reduction in the brain tissue is almost uniform and up to 3.1 degrees C
      temperature drop is achieved within 1 hour. In addition to the possible benefits
      of brain hypothermia for stroke or head injury patients, the device has the
      potential to control fever as well as to improve patients' outcome during open
      neck and head surgery.

PMID- 17429681
TI  - Calpain/calpastatin activities and substrate depletion patterns during hindlimb
      unweighting and reweighting in skeletal muscle.
AB  - Unloading of skeletal muscle by hindlimb unweighting (HU) is characterized by
      atrophy, protein loss, and an elevation in intracellular Ca(2+) levels that may
      be sufficient to activate Ca(2+)-dependent proteases (calpains). In this study,
      we investigated the time course of calpain activation and the depletion pattern
      of a specific structural protein (desmin) with unloading and subsequent
      reweighting. Rats underwent 12 h, 24 h, 72 h or 9 days of HU, followed by
      reweighting for either 0, 12 or 24 h. Total calpain-like activity was elevated
      with HU in skeletal muscle (P < 0.05) and was further enhanced with reweighting
      (P < 0.05). The increases in calpain-like activity were associated with a
      proportional increase in activity of the particulate fraction (P < 0.05).
      Activity of the mu-calpain isoform was elevated with 12 and 24 h of HU (P < 0.05)
      and returned to control levels thereafter. With reweighting, activities of mu
      calpain were elevated above control levels for all HU groups except 9 days (P <
      0.05). In contrast, minimal changes in m-calpain and calpastatin activity were
      observed with HU and reweighting. Although desmin depletion levels did not reach
      statistical significance, a significant inverse relationship was found between
      the mu-calpain/calpastatin ratio and the amount of desmin in isolated myofibrils
      (R = -0.83, P < 0.001). The results suggest that calpain activation is an early
      event during unloading in skeletal muscle, and that the majority of the increase
      in calpain activity can be attributed to the micro-isoform.

PMID- 17429682
TI  - Oxygen uptake kinetics measured at the onset of comfortable self-paced walking in
      elderly women after hip fracture.
AB  - The objectives of this study were to (1) evaluate the suitability of
      "comfortable" self-paced walking as a mode of exercise to study VO(2) kinetics,
      and (2) to investigate VO(2) kinetics after hip fracture using self-paced walking
      as the exercise mode. The study took place in a Scottish rehabilitation hospital
      physiotherapy gymnasium [hip fracture (HF) group] and a Scottish University
      Gymnasium [young (Y) and healthy elderly (HE) groups]. Fifteen women after HF
      (median age 81 years) and five Y and five older HE women (median ages 22 and 78
      years, respectively) took part in the study. Volunteers completed three repeats
      of 3 min of "comfortable" self-paced walking on two occasions. The ensemble
      averaged VO(2) response from walks 2 and 3 on visits 1 and 2 were combined and
      characterised using nonlinear regression techniques to derive a Mean Response
      Time (MRT). Self-paced walking was described as "constant-load" exercise
      (coefficient of variation of lap speeds of <or=6%) in 13 of 15 cases in the HF
      group on at least one visit (100% of cases in Y and HE groups). Steady-state
      VO(2) was achieved in 3 min in 8 of HF group on Visit 1 and 10 on Visit 2 (100%
      of cases in Y and HE groups). MRTs for the HF group (51 s, N = 5, 4 repeats; N =
      7, 2 repeats) were significantly higher than the Y and HE groups [Y group 22 s (N
      = 5, 4 repeats); HE group 36 s (N = 5, 4 repeats)]. Self-paced walking provided a
      suitable mode of exercise to investigate VO(2) kinetics in frail older women
      after HF and permitted the first characterisation of VO(2) kinetics in this
      patient group. This test provides a promising methodology to evaluate
      rehabilitation efforts in frail individuals.

PMID- 17429680
TI  - Brain temperature fluctuations during physiological and pathological conditions.
AB  - This review discusses brain temperature as a physiological parameter, which is
      determined primarily by neural metabolism, regulated by cerebral blood flow, and
      affected by various environmental factors and drugs. First, we consider normal
      fluctuations in brain temperature that are induced by salient environmental
      stimuli and occur during motivated behavior at stable normothermic conditions.
      Second, we analyze changes in brain temperature induced by various drugs that
      affect brain and body metabolism and heat dissipation. Third, we consider how
      these physiological and drug-induced changes in brain temperature are modulated
      by environmental conditions that diminish heat dissipation. Our focus is
      psychomotor stimulant drugs and brain hyperthermia as a factor inducing or
      potentiating neurotoxicity. Finally, we discuss how brain temperature is
      regulated, what changes in brain temperature reflect, and how these changes may
      affect neural functions under normal and pathological conditions. Although most
      discussed data were obtained in animals and several important aspects of brain
      temperature regulation in humans remain unknown, our focus is on the relevance of
      these data for human physiology and pathology.

PMID- 17429683
TI  - The circulating PBEF/NAMPT/visfatin level is associated with a beneficial blood
      lipid profile.
AB  - Visfatin with the official gene name pre-B cell colony-enhancing factor 1 (PBEF)
      and the protein name nicotinamide phosphoribosyltransferase (NAMPT) is a recently
      discovered adipocyte-secreted protein that was shown by some to be associated
      with visceral fat and insulin resistance. To explore the link between
      PBEF/NAMPT/visfatin and lipid metabolism, we analyzed the relation of its plasma
      level with several parameters of adiposity, insulin resistance and the
      circulating blood lipid profile in a group of general population (n = 40) and a
      group of subjects who are genetically predisposed to insulin resistance and
      hyperlipidemia (n = 35). In both groups and pooled cohort, PBEF/NAMPT/visfatin
      lacked association with whole body adiposity, but correlated positively with HDL
      cholesterol and negatively with triglycerides. The data suggested a negative
      correlation of the PBEF level with visceral fat and insulin resistance. But this
      negative correlation completely disappeared after adjustment for lipid profile.
      We concluded that circulating PBEF/NAMPT/visfatin level is an indicator of
      beneficial lipid profile in non-diabetic Caucasian subjects. The relation to
      lipid metabolism does not depend on visceral obesity and insulin resistance, but
      may be linked to its enzymatic function in NAD metabolism.

PMID- 17429684
TI  - An intermediate-conductance Ca(2+)-activated K (+) channel mediates B lymphoma
      cell cycle progression induced by serum.
AB  - We have previously reported that Kv1.3 channel is expressed in Daudi cells.
      However, the present study demonstrates that Daudi cell cycle progression is not
      affected by margatoxin, a Kv1.3 channel blocker, but can be suppressed by
      tetraethylammonium (TEA) and 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole
      (TRAM-34), a selective blocker of intermediate-conductance Ca(2+)-activated K(+)
      (IK) channels. Our patch-clamp data indicate that Daudi cells express an IK
      channel because it has a unit conductance of about 30 pS, is voltage-independent,
      and can be activated by submicromolar Ca(2+) and blocked by TRAM-34. Fetal bovine
      serum (FBS) elevated intracellular Ca(2+) concentration ([Ca(2+)](i)) and
      activated this IK channel. Conversely, Rituximab, a human-mouse chimeric
      monoclonal antibody of CD20, significantly decreased [Ca(2+)](i) and inhibited
      the channel. Furthermore, both FBS-induced IK channel expression and cell cycle
      progression were attenuated by the treatment with LY-294002, a
      phosphatidylinositol 3-kinase (PI3K) inhibitor. These data together suggest that
      a growth factor(s) in FBS triggers cell cycle progression by elevating both IK
      channel activity via CD20 and IK channel expression on the cell surface via PI3K.
      Thus, elevated IK channel activity and expression may account, in part, for Daudi
      cell malignant growth and proliferation.

PMID- 17429685
TI  - Expression patterns of class I KNOX and YABBY genes in Ruscus aculeatus
      (Asparagaceae) with implications for phylloclade homology.
AB  - STM (RaSTM) and YAB2 (RaYAB2) homologues were isolated from Ruscus aculeatus
      (Asparagaceae, monocots), and their expressions were analyzed by real-time
      polymerase chain reaction (PCR) to assess hypotheses on the evolutionary origin
      of the phylloclade in the Asparagaceae. In young shoot buds, RaSTM is expressed
      in the shoot apex, while RaYAB2 is expressed in the scale leaf subtending the
      shoot bud. This expression pattern is shared by other angiosperms, suggesting
      that the expression patterns of RaSTM and RaYAB2 are useful as molecular markers
      to identify the shoot and leaf, respectively. RaSTM and RaYAB2 are expressed
      concomitantly in phylloclade primordia. These results suggest that the
      phylloclade is not homologous to either the shoot or leaf, but that it has a
      double organ identity.

PMID- 17429686
TI  - Differential expression of four protocadherin alpha and gamma clusters in the
      developing and adult zebrafish: DrPcdh2gamma but not DrPcdh1gamma is expressed in
      neuronal precursor cells, ependymal cells and non-neural epithelia.
AB  - Protocadherins are cadherin-like molecules with adhesive and signaling functions,
      in particular, during neuronal development. Large protocadherin (Pcdh) gene
      clusters are present in the genome of vertebrates. In the zebrafish, two Pcdh
      clusters are found on chromosomes 10 (DrPcdh1) and 14 (DrPcdh2), each divided
      into subclusters of DrPcdhalpha and DrPcdhgamma family genes. In total, about 100
      different DrPcdh molecules are predicted. We have analyzed the expression of the
      four DrPcdh subclusters and find that DrPcdh transcripts are upregulated in the
      developing zebrafish nervous system. In the adult fish brain, all four DrPcdh
      clusters are expressed in differentiated neurons, in particular, in the thalamic
      nuclei, tectum, and cerebellum. We show that expression patterns grossly overlap
      for each cluster but with regional differences and variations in strength of
      expression. Strikingly, the DrPcdh2gamma cluster, distinct from the three other
      clusters, is also expressed in neuronal precursor cells and ependymal cells of
      the embryonic and adult nervous system, as well as in specific non-neuronal
      epithelia. Antibodies to a conserved motif in the constant region of DrPcdh2gamma
      stain fiber tracts and neuropil of the zebrafish brain and cell-cell junctions in
      epithelia. Our results indicate that multiple DrPcdhs of the different clusters
      are expressed in differentiated zebrafish neurons, suggesting evolutionarily
      conserved functions of protocadherin clusters in cell adhesion and signaling. In
      addition, DrPcdh2gamma may exert more specific roles in neuronal precursor and
      non-neural epithelial cells, which have not yet been described for mammalian
      Pcdhgamma. Thus, our findings in zebrafish open new perspectives to examine these
      functions in other vertebrate model organisms.

PMID- 17429687
TI  - Claudin expression in pancreatic endocrine tumors as compared with ductal
      adenocarcinomas.
AB  - Altered expression of recently described claudins (CLDNs) as members of tight
      junction (TJ) transmembrane proteins was noted in several malignancies. We aimed
      to analyze protein and messenger RNA (mRNA) expressions of different CLDNs in
      human pancreatic endocrine tumors (PET) and ductal adenocarcinomas. A total of 45
      formalin-fixed, paraffin-embedded samples were studied. Immunohistochemistry and
      real-time reverse transcriptase polymerase chain reaction analysis were carried
      out for quantification of CLDN 1, -2, -3, -4, and -7 expressions. Normal acini
      and ducts showed strong CLDNs 1, -3, -4, and -7 and scattered CLDN 2 protein
      expressions, while Langerhans islands revealed only CLDN 3 and -7 expressions.
      CLDN 2 expression was found in the half of ductal adenocarcinomas, while the vast
      majority of endocrine tumors were negative. CLDN 1, -4, and -7
      immunohistochemistry was positive in all adenocarcinomas, whereas endocrine
      tumors were completely negative for CLDNs 1 and -4. CLDN 3 and -7 proteins were
      detected in all endocrine tumors, while CLDN 3 in ductal adenocarcinomas was
      negative. The mRNA expression of CLDNs showed differences between endocrine
      tumors and ductal adenocarcinomas, similar as found for protein expression. Our
      findings support that PET and ductal carcinomas are specifically characterized by
      different expression pattern of CLDNs. High expressions of CLDN 3 in endocrine
      tumors and CLDN 4 in ductal carcinomas might attract them as targets for adjuvant
      therapy.

PMID- 17429688
TI  - A novel myoepithelial/progenitor cell marker in the breast?

PMID- 17429689
TI  - Expression of nuclear factor kappaB in human gastric carcinoma: relationship with
      I kappaB a and prognostic significance.
AB  - Nuclear factor (NF)-kappaB is a transcription factor constitutively activated in
      various neoplasms, including gastric carcinoma. However, its clinical
      significance in the latter remains an unresolved issue, as published information
      is limited and controversial. Furthermore, no data is available about the
      interaction of NF kappaB with its inhibitory protein I kappaB a in gastric
      carcinoma cases. In this study, the expression of NF kappaB 1/p50 and p I kappaB
      a protein was evaluated immunohistochemically in paraffin-embedded tissues from
      93 patients. The effect of NF kappaB 1/p50 and p I kappaB a on clinical outcome
      was assessed. Positive immunostaining was detected for nuclear NF kappaB 1/p50,
      cytoplasmic NF kappa B1/p50 and p I kappaB a in 91, 68 and 85.7% of cases,
      respectively. A positive correlation emerged between nuclear NF kappa B 1/p50 and
      p I kappaB a (p < 0.0001) and a negative one between cytoplasmic NF kappaB 1/p50
      and p I kappaB a (p = 0.0033). Nuclear NF kappaB 1/p50 was associated with stage
      (p = 0.0388), the depth of invasion (p = 0.0382), World Health Organization (WHO;
      p = 0.0326) and Lauren's histological classification (p = 0.0046). NF kappaB
      1/p50 nuclear expression adversely affected survival in both univariate and
      multivariate analysis (p < 0.0001 and p = 0.02, respectively). Our results
      suggest that NF kappaB 1/p50 nuclear expression and therefore activation is
      regulated by its interaction with I kappaB a and that the former may serve as a
      useful independent molecular marker for stratifying patients with gastric
      carcinoma in terms of prognosis.

PMID- 17429690
TI  - Pathogenesis of leptospirosis: interaction of Leptospira interrogans with in
      vitro cultured mammalian cells.
AB  - Interactions of virulent Leptospira interrogans with murine monocyte-macrophage
      like J774A.1 cells and Vero (African green monkey kidney fibroblasts) cells from
      attachment to internalization were investigated by a series of morphological
      analysis. Fontana silver staining revealed that only the pathogenic leptospires
      were able to attach to host cells and the attachment pattern varied depending on
      cell types that they interacted with. Transmission electron microscopy (TEM)
      analysis confirmed the formation of the leptospires-containing phagosomes and
      their colocalization with lysosomes in macrophages were verified by confocal
      microscopic analysis. Results of F-actin rearrangements examination indicated
      that virulent leptospires invaded host cells via a microfilament-independent
      pathway.

PMID- 17429691
TI  - Confusion over markings on a percutaneous long line.

PMID- 17429692
TI  - Antibody responses in human cystic hydatid disease to the laminated layer of
      Echinococcus granulosus.
AB  - The laminated layer of hydatid cysts of Echinococcus granulosus represents a
      considerable amount of parasite material. Its antigenic role, however, is
      unclear. Extracts of laminated layer taken from sheep cysts were analysed in
      sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS/PAGE) and were
      found to contain bands at 55 and 25-29 kDa, which reacted with an anti-sheep IgG
      antibody probe, indicating that these were likely to be host-contaminating
      components within the layer. However, the same bands were also recognised by a
      significant proportion of human hydatid patients, particularly by IgG4
      antibodies, and not by negative control individuals. These individuals did not
      recognise immunoglobulin heavy and light chains in a sheep serum extract in the
      same manner. It seems likely that there are either host or parasite antigenic
      components at similar molecular weights or that certain parasite antigens may
      share epitopes with sheep immunoglobulins. The antigens at 25-29 kDa were found
      to be glycoproteins by lectin blot analysis and may be important markers of
      disease status.

PMID- 17429693
TI  - Structure and allele-specific expression variation of novel alpha/beta hydrolase
      fold proteins in gentian plants.
AB  - Previously, we identified two closely related proteins termed W14 and W15 that
      were enriched in the overwinter buds of the gentian plant Gentiana triflora.
      Expression of the latter protein W15 has been implicated in its association with
      cold hardiness, because of its absence in a cold-sensitive mutant. Here, we
      characterized these two proteins and the genes encoding them. Amino acid
      sequences of the W14 and W15 proteins showed difference at only three amino acid
      positions, and both of them showed homologies to alpha/beta hydrolase fold
      superfamily. Consistently, GST-fused W14 and W15 proteins expressed in bacteria
      showed hydrolase activity toward 1-naphtyl acetate. Structural analysis of these
      two genes in seven different gentian strains/cultivars including an anther
      culture-derived homozygous diploid revealed that W14 and W15 genes are allelic.
      Three genotypes were found; two strains carried both alleles (W14/W15), one
      carried the W15 genes in both alleles (W15/W15), and others were homozygous of
      W14 (W14/W14). Interestingly, expression of the two proteins exhibited allele
      specificity. In one W14/W15 strain, expression of the W15 allele was almost
      repressed. In addition, organ specific expression of the alleles was observed in
      different cultivars. These observations were discussed in relation to winter
      hardiness of the gentian plants.

PMID- 17429694
TI  - Premature progression of anther early developmental programs accompanied by
      comprehensive alterations in transcription during high-temperature injury in
      barley plants.
AB  - High-temperature stress causes abortive male reproductive development in many
      plant species. Here, we report a putative mechanism of high-temperature injury
      during anther early development in barley plants (Hordeum vulgare L). Under high
      temperature conditions (30 degrees C day/25 degrees C night), cell-proliferation
      arrest, increased vacuolization, over-development of chloroplasts, and certain
      abnormalities of the mitochondria, nuclear membrane, and rough endoplasmic
      reticulum (RER) were observed in developing anther cells, but not in developing
      ovule cells. Moreover, premature degradation of tapetum cells and premature
      progression to meiotic prophase in pollen mother cells (PMCs) were also observed.
      To monitor transcriptional alterations during high-temperature injury, we
      performed DNA microarray analysis using the 22K Barley1 GeneChip. Expression
      profiles were captured at four time points during the early development of
      panicles, and during vegetative growth of seedlings as a control, with or without
      high-temperature treatment. Abiotic or biotic stress related genes were equally
      or more dominantly up-regulated in the seedlings exposed to high temperatures
      compared with the panicles. In contrast, certain genes associated with histones,
      DNA replication initiation, mitochondria, and ribosomes were specifically
      repressed in the exposed panicles. In situ hybridization studies indicated that
      repression locally occurred on the developing anther cells exposed to high
      temperatures. Microarray analysis also indicated that a series of genes,
      including a meiosis-specific gene Asy1 and anther-specific lipid transfer protein
      genes, was prematurely up-regulated at an earlier stage under high-temperature
      conditions. Real-time quantitative RT-PCR analyses well confirmed the expression
      differences of certain key genes predicted by the DNA microarrays. These results
      suggest that high-temperature causes premature progression of anther early
      development program and fate, such as progression to meiosis of PMCs, cell
      proliferation arrest and degradation in anther wall cells, accompanied by
      comprehensive alterations in transcription.

PMID- 17429696
TI  - BMP2, BMP4, and their receptors are expressed in the differentiating muscle
      tissues of mouse embryonic tongue.
AB  - To investigate the role of bone morphogenetic proteins (BMPs) in the
      differentiation process of skeletal muscle, we analyzed the in vivo expression of
      BMP2 and BMP4, of BMP receptors (BMPR) IA, IB, and II, and of activin receptors
      (ActR) IA, II, and IIB in mouse tongue muscle between embryonic day 11 (E11) and
      E17. The mRNA expression levels for BMP2 were 5-fold to 11-fold greater than
      those for BMP4 between E13 and E17 (P < 0.05-0.01). Expression of the BMP2,
      BMPRIB, ActRIA, ActRII, and ActRIIB proteins was first observed at E13.
      Expression of BMP2 and BMPRIB was detected in the whole area of the
      differentiating muscle tissues identified by immunostaining for fast myosin heavy
      chain (fMHC), but that of ActRIA, ActRII, and ActRIIB was detected only in the
      peripheral area of the differentiating muscle tissues. In the E15 tongue, all of
      the BMPs, BMPRs, and ActRs studied herein were expressed in the whole area of the
      differentiating muscle tissues identified by immunostaining for fMHC. These
      results suggest that BMPs play a role in the differentiation of tongue muscle
      tissues at E15 but have little or no effect at E13.

PMID- 17429695
TI  - Molecular characterization of the Rpt1/p48B ATPase subunit of the Drosophila
      melanogaster 26S proteasome.
AB  - The function and the molecular properties of the Rpt1/p48B ATPase subunit of the
      regulatory particle of the Drosophila melanogaster 26S proteasome have been
      studied by analyzing three mutant Drosophila stocks in which P-element insertions
      occurred in the 5'-non-translated region of the Rpt1/p48B gene. These P-element
      insertions resulted in larval lethality during the second instar larval phase.
      Since the Rpt1/p48B gene resides within a long intron of an annotated, but
      uncharacterized Drosophila gene (CG17985), the second instar larval lethality may
      be a consequence of a combined damage to two independent genes. To analyze the
      phenotypic effect of the mutations affecting the Rpt1/p48B gene alone, imprecise
      P-element excision mutants were selected. One of them, the pupal lethal P1
      mutation, is a hypomorphic allele of the Rpt1/p48B gene, in which the
      displacement of two essential regulatory sequences of the gene occurred due to
      the insertion of a 32 bp residual P-element sequence. This mutation caused a 30
      fold drop in the cellular concentration of the Rpt1/p48B mRNA. The decline in the
      cellular Rpt1/p48B protein concentration induced serious damage in the assembly
      of the 26S proteasomes, the accumulation of multiubiquitinated proteins, a change
      in the phosphorylation pattern of the subunit and depletion of this ATPase
      protein from the chromatin.

PMID- 17429697
TI  - Gamma-aminobutyric acid and related molecules in the sea fan Eunicella cavolini
      (Cnidaria: Octocorallia): a biochemical and immunohistochemical approach.
AB  - The aim of this study has been the biochemical demonstration of the presence of
      gamma-aminobutyric acid (GABA) in the Mediterranean sea fan Eunicella cavolini by
      means of high-performance liquid chromatography, and the description of the
      distribution pattern of GABA and its related molecules, glutamic acid
      decarboxylase (GAD), vesicular GABA transporter (VGAT) and one of the GABA
      receptors (GABA(B) R) by immunohistochemical methods. The interrelationships of
      GABA, GAD and GABA receptor immunoreactivity have been established by using
      double-immunohistochemical methods and confocal microscopy. The immunodetection
      of monoclonal and/or polyclonal antibodies has revealed GABA immunoreactivity
      throughout the polyp tissue, both in neuronal and non-neuronal elements. GAD
      immunoreactivity has been mostly localized in the neuronal compartment,
      contacting epithelial and muscular elements. GABA(B) R immunoreactivity appears
      particularly intense in the nematocytes and in the oocyte envelope; its presence
      in GAD-immunoreactive neurons in the tentacles suggests an autocrine type of
      regulation. Western blot analysis has confirmed that a GABA(B) R, with a
      molecular weight of 142 kDa, similar to that of rat brain, is present in E.
      cavolini polyp tissue. The identification of the sites of the synthesis,
      vesicular transport, storage and reception of GABA strongly suggests the presence
      of an almost complete set of GABA-related molecules for the functioning of the
      GABAergic system in this simple nervous system. The distribution of these
      different immunoreactivities has allowed us to hypothesize GABA involvement in
      nematocyst discharge, in body wall and enteric muscular contraction, in neuronal
      integration and in male gametocyte differentiation.

PMID- 17429698
TI  - Impact of soil vertical water movement on the energy balance of different land
      surfaces.
AB  - The soil heat flux determination method proposed by Gao (Boundary-Layer Meteorol
      114:165-178, 2005) is discussed for (1) dry surfaces, (2) bare soil or sparse
      short-grass lands, and (3) dense-grass surfaces or forest. Our analysis shows
      that, when neglecting the contribution of soil vertical water movement to soil
      heat flux, the energy components measured independently will (1) still achieve
      balance over dry surfaces, and (2) be significantly in imbalance over bare soil
      or sparse short-grass lands. The mean of bare ground evaporation modeled by SiB2
      is 1.58 x 10(-5) m(3) s(-1) m(-2), and the mean of soil water flux obtained by
      the method of Gao is 1.22 x 10(-5) m(3) s(-1) m(-2) for the Naqu site in the
      summer of 1998. Comparison of the bare ground evaporation with the mean of soil
      water flux shows a difference, the causes of which are investigated. Physically,
      the bare ground evaporation is equal to the sum of soil water flux and water
      content change in the soil surface layer. Because the bare ground evaporation is
      very limited for the dense-grass surfaces or forest, our analysis implies that
      the energy imbalance encountered over the dense-grass or forest is not caused by
      the fact that previous researchers neglected soil water movements in their energy
      budget analyses.

PMID- 17429699
TI  - Symptom and medication profiles among cancer patients attending a palliative care
      clinic.
AB  - BACKGROUND: Patients with advanced cancer frequently experience distressful
      symptoms and receive numerous medications. We describe the symptomatology and
      medication profile of ambulatory cancer patients receiving exclusively supportive
      care at the Princess Margaret Hospital. MATERIALS AND METHODS: This was a
      retrospective, cross-sectional study. We reviewed the charts of consecutive adult
      cancer patients attending palliative care clinics and who were no longer
      receiving cancer-directed therapy. From the medical records, we collected
      information about self-reported symptoms [screened for with the numerical
      Edmonton symptom assessment system (ESAS) scale; range, 0-10, with 10=worst
      symptom] and medication profiles. Summary statistics were used to describe the
      results. RESULTS: Two hundred fifty five patients met the inclusion criteria. The
      most frequent self-reported symptoms of any severity were fatigue (77%), pain
      (75%), and lack of appetite (66%). These were also the most severe symptoms:
      fatigue (median ESAS score=7), pain (median ESAS=5), and lack of appetite (median
      ESAS=5). The median number of medications per patient after consultation in the
      palliative care service was 6, and the most common classes of drugs prescribed
      were opioids (67%), laxatives/stool softeners (54%), corticosteroids (41%), and
      acetaminophen (41%). Palliative care physicians made at least one medication
      change in 75% of the patients, with the most frequent change being the addition
      of new medication(s); dexamethasone was the most commonly added individual drug
      (18% of the patients). CONCLUSION: Among patients with advanced cancer not
      receiving antineoplastic therapy, the most frequent and severe symptoms were
      fatigue, pain, and lack of appetite. The medication profile represented drugs
      that could both alleviate and contribute to these symptoms. Audit of patient
      symptoms and medication prescription in palliative care may inform clinical
      practice and help the development of research specific to patient symptoms.

PMID- 17429700
TI  - Using terminal restriction fragment length polymorphism (T-RFLP) to identify
      mycorrhizal fungi: a methods review.
AB  - Terminal restriction fragment length polymorphism (T-RFLP) is an increasingly
      widely used technique in mycorrhizal ecology. In this paper, we review the
      technique as it is used to identify species of mycorrhizal fungi and distinguish
      two different versions of the technique: peak-profile T-RFLP (the original
      version) and database T-RFLP. We define database T-RFLP as the use of T-RFLP to
      identify individual species within samples by comparison of unknown data with a
      database of known T-RFLP patterns. This application of T-RFLP avoids some of the
      pitfalls of peak-profile T-RFLP and allows T-RFLP to be applied to polyphyletic
      functional groups such as ectomycorrhizal fungi. The identification of species
      using database T-RFLP is subject to several sources of potential error, including
      (1) random erroneous matches of peaks to species, (2) shared T-RFLP profiles
      across species, and (3) multiple T-RFLP profiles within a species. A mathematical
      approximation of the risk of the first type of error as a function of
      experimental parameters is discussed. Although potentially less accurate than
      some other methods such as clone libraries, the high throughput of database T
      RFLP permits much greater replication and may, therefore, be preferable for many
      ecological questions, particularly when combined with other techniques such as
      cloning.

PMID- 17429701
TI  - Spinal mechanical load: a predictor of persistent low back pain? A prospective
      cohort study.
AB  - Prospective inception cohort. To assess the prognostic value of spinal mechanical
      load, assessed with the 24-hour schedule (24HS), in subjects with acute non
      specific low back pain (ALBP) and to examine the influence of spinal mechanical
      load on the course of ALBP. In view of the characteristics of the natural course
      of ALBP, this should be viewed as a persistent condition in many patients rather
      that a benign self-limiting disease. Therefore, secondary prevention could be
      beneficial. Spinal mechanical load is a risk factor for ALBP and possibly a
      (modifiable) prognostic factor for persistent (i.e. recurrent and/or chronic)
      LBP. One hundred patients from primary care with ALBP were eligible for
      inclusion. At 6 months, 88 subjects completed the follow-up. For the follow-up
      assessment a research assistant, unaware of our interest in the prognostic
      factors, contacted the subjects by telephone. Questionnaires were completed
      focusing on changes in demographic data and on the course and current status of
      ALBP. Persistent LBP occurred in 60% subjects. After multivariate regression
      analysis smoking (harmful) and advanced age (protective) were associated with
      persistent LBP. Differences in 24HS scores at baseline and follow-up were
      univariate-related to persistent LBP. Spinal mechanical load, quantified with the
      24HS, is not a prognostic factor for persistent LBP. Modification of spinal
      mechanical load in terms of 24HS scores could be beneficial for secondary
      prevention in patients with acute LBP.

PMID- 17429702
TI  - The role of non-need factors in individual GP utilisation analysis and their
      implications for the pursuance of equity: a cross-country comparison.
AB  - A substantial amount of health care resources is allocated within the UK using
      formulae that relate funding to measures of population need. The aim of this
      paper is to demonstrate the importance of non-need factors in determining
      utilisation of services at an individual level and explore the implications
      inclusion of such factors has in the consideration of equity. In the paper we
      develop a utility model that accords a role to non-health factors in the
      determination of service use. A series of functions incorporating non-health
      factors as explanatory variables in GP utilisation functions are estimated using
      data from the British Household Panel Survey. The functions are decomposed to
      ascertain the role of service structure and examine the role of income across the
      four countries of the UK in explaining utilisation. The implications of our
      findings for the pursuance of equity in the NHS when individual choice has an
      explicit role are discussed.

PMID- 17429703
TI  - Reproducibility of continuous arterial spin labeling perfusion MRI after 7 weeks.
AB  - BACKGROUND: Continuous arterial spin labeling (CASL) is a non-invasive technique
      for the measurement of cerebral blood flow (CBF). The aim of the present study
      was to examine the reproducibility of CASL measurements and its suitability to
      consistently detect differences between groups, regions, and resting states.
      MATERIALS AND METHODS: Thirty-eight healthy subjects (19 female) were examined at
      1.5 T on two measurement occasions that were seven weeks apart. Resting CBF was
      measured with eyes open and eyes closed. RESULTS: In different regions of
      interest (ROIs) the repeatability estimates varied between 9 and 19 ml/100 g/min.
      There were no significant mean differences between occasions in all ROIs (P >
      0.05). Greater CBF in the eyes-open than in the eyes-closed state was
      consistently present in the primary and secondary visual areas. Furthermore, CBF
      was consistently greater in the right than in the left hemisphere (P < 0.05) and
      differed between lobes and between arterial territories (P < 0.001). Finally, we
      consistently observed greater CBF in women than in men (P < 0.001). CONCLUSION:
      This study demonstrates the suitability of CASL to consistently detect
      differences between groups, regions, and resting states even after seven weeks.
      This emphasizes its usefulness for longitudinal designs.

PMID- 17429704
TI  - Predictive coding: an account of the mirror neuron system.
AB  - Is it possible to understand the intentions of other people by simply observing
      their actions? Many believe that this ability is made possible by the brain's
      mirror neuron system through its direct link between action and observation.
      However, precisely how intentions can be inferred through action observation has
      provoked much debate. Here we suggest that the function of the mirror system can
      be understood within a predictive coding framework that appeals to the
      statistical approach known as empirical Bayes. Within this scheme the most likely
      cause of an observed action can be inferred by minimizing the prediction error at
      all levels of the cortical hierarchy that are engaged during action observation.
      This account identifies a precise role for the mirror system in our ability to
      infer intentions from actions and provides the outline of the underlying
      computational mechanisms.

PMID- 17429706
TI  - Delayed rectovaginal fistula: a potential complication of bevacizumab (avastin).

PMID- 17429705
TI  - Cognition as coordinated non-cognition.
AB  - We propose that cognition is more than a collection of independent processes
      operating in a modular cognitive system. Instead, we propose that cognition
      emerges from dependencies between all of the basic systems in the brain,
      including goal management, perception, action, memory, reward, affect, and
      learning. Furthermore, human cognition reflects its social evolution and context,
      as well as contributions from a developmental process. After presenting these
      themes, we illustrate their application to the process of anticipation.
      Specifically, we propose that anticipations occur extensively across domains
      (i.e., goal management, perception, action, reward, affect, and learning) in
      coordinated manners. We also propose that anticipation is central to situated
      action and to social interaction, and that many of its key features reflect the
      process of development.

PMID- 17429707
TI  - The clinical and endoscopic characteristics, treatment, and long-term prognosis
      of early colorectal cancer in Taiwan.
AB  - PURPOSE: This study was designed to realize the incidence, clinical and
      endoscopic characteristics, treatment, and prognosis of early colorectal cancer
      in Taiwan. METHODS: A retrospective study was conducted to review the data from
      January 1, 1991 to December 31, 2005 at the National Taiwan University Hospital.
      Patients' clinical information, demographic data, endoscopic pictures, treatment
      regimens, pathologic, and outcome details for these cases were reviewed,
      recorded, and analyzed. Mann-Whitney U test and log-rank test were used for the
      statistical analysis. RESULTS: A total of 61 patients from this 15-year period
      were included (39 males; mean age of disease onset, 63.5 years). The follow-up
      period ranged from 0.05 to 15 (mean, 6.8) years. Five-year survival rate in our
      early colorectal cancer patients was 98.4 percent. The size of the early
      colorectal cancer ranged from 0.3 to 5 cm with the mean of 1.4 cm. The most
      common site of early colorectal cancer was the sigmoid colon (56.1 percent).
      Protruded (Type I) lesions accounted for the majority (73.6 percent) of the
      cases. Endoscopic polypectomy/mucosectomy was the most common type of treatment
      (72.3 percent). There was no statistical difference in the survival status
      between the endoscopic treatment group and the operation group (log-rank test, P
      = 0.368). CONCLUSIONS: Most of the early colorectal cancer lesions could be
      removed successfully by endoscopic method without mortality and major morbidity.
      However, regular follow-up after treatment is recommended even after five years
      to reduce early colorectal cancer mortality and morbidity.

PMID- 17429708
TI  - Prognostic significance of receptor-binding cancer antigen expressed on SiSo
      cells (RCAS1) expression in relation to cadherin expression in patients with
      colorectal carcinoma.
AB  - PURPOSE: This study was designed to assess the prognostic value of receptor
      binding cancer antigen expressed on SiSo cells expression and its relationship
      with cadherin expression in patients with colorectal cancer. METHODS: The
      expressions of receptor-binding cancer antigen expressed on SiSo cells and E
      cadherin were analyzed with special reference to prognosis in 105 patients with
      colorectal cancer. RESULTS: Receptor-binding cancer antigen expressed on SiSo
      cells immunoreactivity was detected in the membrane and cytoplasm of tumor cells
      and considered to be positive in 48 patients (45.7 percent). The expression of
      receptor-binding cancer antigen expressed on SiSo cells was significantly
      correlated with lymph node metastasis (P = 0.0004), venous invasion (P = 0.0062),
      Dukes stages (P < 0.0001), and serum levels of carcinoembryonic antigen (P =
      0.014). Furthermore, receptor-binding cancer antigen expressed on SiSo cells
      expression was significantly correlated with a poor prognosis (P < 0.001), and
      multivariate analysis indicated that it was an independent prognostic indicator.
      The expression of receptor-binding cancer antigen expressed on SiSo cells was
      more frequently found in tumors with reduced or abnormal expression of E
      cadherin. The survival time of patients with reduced/abnormal E-cadherin
      expression was significantly shorter than that of patients with normal E-cadherin
      expression among patients with receptor-binding cancer antigen expressed on SiSo
      cells expression (P = 0.0043) but did not differ for those without receptor
      binding cancer antigen expressed on SiSo cells expression (P = 0.17).
      Furthermore, multivariate analysis revealed that reduced/abnormal expression of E
      cadherin was an independent prognostic factor in patients with receptor-binding
      cancer antigen expressed on SiSo cells expression but not in those without
      receptor-binding cancer antigen expressed on SiSo cells expression. CONCLUSIONS:
      Receptor-binding cancer antigen expressed on SiSo cells expression is
      significantly correlated with tumor progression and poor prognosis in patients
      with colorectal cancer. Both reduced E-cadherin and enhanced receptor-binding
      cancer antigen expressed on SiSo cells expression may be critical for the
      mechanism of metastasis and recurrence in human colorectal cancer.

PMID- 17429709
TI  - Pathologic determinants of survival after resection of T3N0 (Stage IIA)
      colorectal cancer: proposal for a new prognostic model.
AB  - PURPOSE: There is an increasing need for accurate prognostic stratification of
      patients with Stage II colorectal cancer to identify a subgroup of high-risk
      patients who may benefit from adjuvant therapies. This study was designed to
      evaluate the prognostic impact of a wide spectrum of pathologic parameters in a
      consecutive series of homogenously treated and well-characterized patients with
      Stage IIA (T3N0M0) colorectal cancer. METHODS: The study included 238 patients
      operated on by a single surgeon for Stage IIA colorectal tumors. The median
      postoperative follow-up was 110 (range, 96-120) months. At least 12 lymph nodes
      were harvested and examined in all the resection specimens. The prognostic value
      of 13 pathologic parameters, including lymph node occult disease
      (micrometastases) detected by immunohistochemistry, was investigated. RESULTS:
      Multivariate analysis identified tumor growth pattern (expanding or infiltrating;
      P = 0.01) and extent of tumor spread beyond muscularis propria (< or =5 mm or >5
      mm; P = 0.04) as the only factors having independent prognostic value. The
      combination of these two easily determined parameters allowed us to identify two
      groups of patients at low risk or high risk of tumor recurrence. The eight-year
      survival rates were 83.3 and 53.4 percent for the two groups, respectively. The
      high-risk group comprised those patients with infiltrating tumors and extramural
      tumor spread > 5 mm. CONCLUSIONS: We propose a new and simple prognostic model to
      identify patients with high-risk Stage IIA colorectal cancer for whom adjuvant
      therapies may be justified and effective.

PMID- 17429710
TI  - Functional outcome after transperineal rectocele repair with porcine dermal
      collagen implant.
AB  - PURPOSE: Symptomatic rectocele results in obstructed defecation and constipation.
      Surgical repair may provide symptomatic relief. This study was designed to assess
      the safety and efficacy of transperineal rectocele repair with porcine dermal
      collagen (Permacol). METHODS: Ten females with symptomatic rectocele had a
      transperineal repair using Permacol. Median age was 51 (range, 33-71) years.
      Patients were followed with detailed interviews at a median time of 9 (range, 5
      16) months. Objective preoperative and postoperative assessment was by outcomes
      for five symptoms: constipation, excessive straining, incomplete evacuation,
      vaginal bulging, and vaginal digitations (always, usually, occasionally, never),
      and Medical Outcomes Study Short Form 36 questionnaires. Subjective outcomes were
      assessed as excellent, good, moderate, and poor. RESULTS: All patients had an
      improvement in two or more symptoms and 70 percent of patients in three or more
      symptoms. Postoperatively 80 percent reported an improvement in excessive
      straining (P = 0.0078) and in incomplete evacuation (P = 0.0078); 70 percent
      reported an improvement in vaginal bulging (P = 0.0156). Improvements in vaginal
      digitations and Medical Outcomes Study Short Form 36 scores were not
      statistically significant. Subjective outcomes were reported as excellent or good
      by 80 percent of patients. No patients had rectal perforation or infection, and
      no Permacol has been removed. CONCLUSIONS: Rectocele repair with Permacol((R)) by
      the transperineal approach is a safe technique that avoids some of the
      complications associated with synthetic mesh use. Objective and subjective
      results are excellent in the majority of patients.

PMID- 17429711
TI  - Mucosal dysplasia in ileal pelvic pouches after restorative proctocolectomy.
AB  - PURPOSE: Inflammation, villous atrophy, colonic metaplasia, and dysplasia have
      been observed within the mucosa of ileal pelvic pouches after restorative
      proctocolectomy. This study was designed to determine the prevalence of mucosal
      dysplasia in ileal pouch and any associated risk factors. METHODS: Prospectively
      registered patients having restorative proctocolectomy were recruited. A cross
      sectional study was performed using a questionnaire focusing on disease history,
      functional results, and pouchitis after surgery. Participants underwent screening
      endoscopic pouch examination using sigmoidoscopy. Mucosal biopsies were taken
      from six specific locations in the pouch from proximal ileal-pouch (inflow) to
      ileoanal anastomosis. All biopsies were performed under strict surveillance
      protocol regardless of patients' symptoms. Biopsies were interpreted by two
      pathologists unaware of each other's report. RESULTS: A total of 138 patients
      completed the protocol. Colectomy specimens from restorative proctocolectomy
      showed chronic ulcerative colitis in 118 (85.6 percent), familial adenomatous
      polyposis in 10 (7.2 percent), Crohn's colitis in 2 (1.4 percent), and
      indeterminate colitis in 8 (5.8 percent) patients. Twenty-two patients (18.3
      percent) had dysplasia and eight (6.7 percent) had invasive cancer found in
      colectomy specimens after restorative proctocolectomy. Median interval between
      proctocolectomy and pouch biopsy was 5.4 years. Inflammatory changes were present
      in a majority of specimens, but these did not correlate with clinical history of
      pouchitis. No villous atrophy was identified. Pouch biopsies from only one
      patient were indefinite for dysplasia. Subsequent biopsies were negative.
      CONCLUSIONS: Clinical and microscopic evidence of ileal-pouch inflammation is
      common. Ileal-pouch mucosal dysplasia is uncommon, occurring in only 1 of 138
      patients. Villous atrophy and colonic metaplasia were not observed in this
      series. Routine pouch surveillance with biopsies may not be warranted.

PMID- 17429712
TI  - Prebiotic and synbiotic fructooligosaccharide administration fails to reduce the
      severity of experimental colitis in rats.
AB  - Opposing effects of the prebiotic, fructooligosaccharide, have been reported in
      experimental colitis. We compared the effects of the prebiotic,
      fructooligosaccharide, alone and in synbiotic combination with Lactobacillus
      fermentum BR11, on the development of dextran sulfate sodium-induced colitis in
      rats. Rats consumed an 18 percent casein-based diet or diet supplemented with 6
      percent fructooligosaccharide or maltodextrin for 14 days. The synbiotic group
      was gavaged 1 ml of L. fermentum BR11 (1x10(9) cfu/ml) twice daily. From Days 7
      to 14, colitis was induced via 3 percent dextran sulfate sodium in drinking
      water. Disease activity was assessed daily, and at killing, gastrointestinal
      organs were measured, weighed, and examined by quantitative histology,
      proliferating cell nuclear antigen immunohistochemistry, and colonic
      myeloperoxidase activity. Administration of dextran sulfate sodium resulted in an
      increased colitic disease activity, and an increased colon and cecum weight
      compared with normal controls. Colon and cecum weights were further increased in
      dextran sulfate sodium+fructooligosaccharide (colon: 19 percent; cecum: 48
      percent) and dextran sulfate sodium+fructooligosaccharide/L. fermentum BR11
      treated rats (16 and 62 percent) compared with dextran sulfate sodium+vehicle
      treatment. Dextran sulfate sodium+fructooligosaccharide-treated rats displayed an
      81 percent increase in colonic myeloperoxidase activity compared with dextran
      sulfate sodium-treated controls. Histologic damage severity scores increased in
      dextran sulfate sodium+vehicle, dextran sulfate sodium+fructooligosaccharide, and
      dextran sulfate sodium+fructooligosaccharide/L. fermentum BR11-treated rats
      compared with normal controls (P<0.05). Crypt depth increased in all treatments
      compared with normal controls (P<0.01). No protection from dextran sulfate sodium
      colitis was accorded by fructooligosaccharide alone or in synbiotic combination
      with L. fermentum BR11, whereas fructooligosaccharide actually increased some
      indicators of colonic injury.

PMID- 17429713
TI  - Prevalence and risk factors for anal cytologic abnormalities and human
      papillomavirus infection in a rural population of HIV-infected males.
AB  - PURPOSE: This study was designed to determine the prevalence and risk factors for
      anal squamous intraepithelial lesions and human papillomavirus infection in a
      rural population of HIV-infected males. METHODS: A cross-sectional study was
      performed. Risk factors were collected. Anal Papanicolaou smear and human
      papillomavirus screening for oncogenic types were performed. RESULTS: Of 211
      eligible male patients, 149 (70.6 percent) participated. HIV transmission risk
      was predominantly males who have sex with males (82 percent). The mean duration
      of HIV infection was 9.9 years. Ninety (60 percent) males had abnormal anal
      cytology, including atypical cells of unknown significance 40 (26 percent), low
      grade squamous intraepithelial lesions 28 (19 percent), and high-grade squamous
      intraepithelial lesions 22 (15 percent). Human papillomavirus was detected in 61
      percent. Binary logistic regression adjusted risks for abnormal anal cytology
      included: males who have sex with males (P<0.001), human papillomavirus infection
      (P<0.001), history of anogenital warts (P=0.014), and the mean lowest CD4 count
      (abnormal cytology, 158 (standard deviation, 135), negative cytology, 208
      (standard deviation, 180; P=0.017)). Twenty-two patients with high-grade squamous
      intraepithelial lesions underwent colorectal surgical examination and anoscopy.
      Two (10 percent) were found to have invasive squamous-cell carcinoma and three
      (15 percent) others had mass lesions with high-grade squamous intraepithelial
      lesions. CONCLUSIONS: Anal squamous intraepithelial lesions and oncogenic human
      papillomavirus are highly prevalent in males infected with HIV and living in a
      rural setting.

PMID- 17429715
TI  - Amyand and de Garengeot' hernias.

PMID- 17429714
TI  - Repair of giant incisional abdominal wall hernias using open intraperitoneal
      mesh.
AB  - BACKGROUND: Very large and complex incisional hernias, especially those involving
      loss of abdominal wall, present a particular challenge to the surgeon. AIMS: The
      open intraperitoneal technique was used prospectively for the repair of
      incisional hernias in a selected group of patients with large defects, often
      those with major loss of abdominal wall, overweight patients, and previous
      failures of incisional repair. MATERIALS AND METHODS: Between 1 January 1999 and
      31 December 2005, out of 275 patients operated on for incisional hernia repair,
      61 of them, most of whom were obese with multiorificial recurrent or giant
      hernias and contraindicated for laparoscopy, were treated using an open
      intraperitoneal mesh technique. There were 50 females and 11 males, with a mean
      age of 61. The median ASA score of the group was 2.3, with a mean BMI of 34
      kg/m(2) and a mean hernia surface of 182 cm(2). Sixty-four percent of the
      patients had undergone one or more previous incisional hernia repairs. RESULTS:
      Mean operating time was 130 min, with an average hospital stay of 13 days. None
      of the patients died. Postoperative complications occurred in 21% of the
      patients; most of which were minor, but two cases (3.3%) developed deep abscesses
      requiring surgery and removal of the mesh. A recurrence rate of 5% was found
      after a mean follow-up of 35 months (8-88). CONCLUSION: Open intraperitoneal mesh
      repair appears to be a good option for the treatment of complex incisional hernia
      (at least 10 cm in diameter or multiorificial) in obese patients contraindicated
      for laparoscopy.

PMID- 17429716
TI  - Genetic analysis of two influenza A (H1) swine viruses isolated from humans in
      Thailand and the Philippines.
AB  - Influenza viruses A/Philippines/341/2004 (H1N2) and A/Thailand/271/2005 (H1N1)
      were isolated from two males, with mild influenza providing evidence of sporadic
      human infection by contemporary swine influenza. Both viruses were antigenically
      and genetically distinct from influenza A (H1N1 and H1N2) viruses that have
      circulated in the human population. Genetic analysis of the haemagglutinin genes
      found these viruses to have the highest degree of similarity to the classical
      swine H1 viruses circulating in Asia and North America. The neuraminidase gene
      and the internal genes were found to be more closely related to viruses
      circulating in European swine, which appear to have undergone multiple
      reassorting events. Although transmission of swine influenza to humans appears to
      be a relatively rare event, swine have been proposed as the intermediate host in
      the generation of potential pandemic influenza virus that may have the capacity
      to cause human epidemics resulting in high morbidity and mortality.

PMID- 17429717
TI  - Evaluation of radiolabeled bombesin analogs in animals.

PMID- 17429718
TI  - Is cognitive dysfunction a complication of adjuvant chemotherapy in the older
      patient with breast cancer?
AB  - For a number of years, patients have anecdotally reported changes in memory and
      concentration problems after receiving chemotherapy for breast cancer.
      Neuropsychological studies have been performed to seek objective evidence as to
      the existence and extent of this phenomenon; however, these studies were
      primarily performed in younger women and there is sparse data regarding the
      impact of adjuvant chemotherapy on an older woman's cognition. The objective of
      this paper was to evaluate the current literature in order to propose ways to
      overcome methodological limitations of studies to consider whether chemotherapy
      associated cognitive dysfunction exists in older patients and if so, who is at
      risk. A systematic review of relevant literature was performed including study
      design, mean age of participants, treatment received, neuropsychological tests
      employed, timing of assessments, definition of cognitive impairment, and results.
      The literature primarily consists of small studies, which lack a prospective
      longitudinal design, vary in design measures, and exclude older patients who are
      at greatest risk for cognitive impairment. Since aging is the number one risk
      factor for breast cancer, future studies of the neuropsychological impact of
      chemotherapy should include older patients.

PMID- 17429719
TI  - Corticosteroid-responsive cryptogenic chronic hepatitis: evidence for
      seronegative autoimmune hepatitis.
AB  - Cryptogenic chronic hepatitis (CCH) is diagnosed in patients with persistently
      elevated aminotransferase levels of unknown etiology. The workup of CCH patients
      must include a liver biopsy in order to exclude the largely unrecognized
      diagnosis of seronegative autoimmune hepatitis (SAIH). Patients with SAIH have
      demographic, biochemical, and histologic features of autoimmune hepatitis (AIH)
      and may be treated effectively with corticosteroids. Recognition and treatment of
      SAIH are necessary to prevent progression to end-stage liver disease. We
      performed a retrospective review of a database of 3507 patients seen at our
      institution over a 5-year period. Thirty patients with conventional AIH and an
      additional six patients with SAIH were identified. The two groups were similar
      with respect to mean age, gender, and baseline biochemistry. Of the 20 AIH
      patients who had pretreatment liver biopsies, 85% had moderate to severe
      interface hepatitis, compared to 83.3% of patients with SAIH. In the SAIH group,
      83.3% had advanced fibrosis (stage 3 or 4), versus 40% in the conventional AIH
      group (P = 0.16). All patients were treated with corticosteroids followed by
      azathioprine. The mean time to remission (normal ALT) was similar in both groups,
      2.6 vs. 2.7 months. Within 3 months, 88.9% of AIH patients and 66.7% of SAIH
      patients were in remission. We conclude that a trial of corticosteroids is a
      reasonable therapeutic measure in patients with chronic hepatitis that has
      features of AIH despite negative autoantibody markers. In most patients, clinical
      remission will be seen within 3 months, possibly avoiding progression to end
      stage liver disease.

PMID- 17429720
TI  - Aggravation by selective COX-1 and COX-2 inhibitors of dextran sulfate sodium
      (DSS)-induced colon lesions in rats.
AB  - We examined the effect of cyclooxygenase (COX) inhibitors on dextran sulfate
      sodium (DSS)-induced ulcerative colitis in rats and investigated the role of COX
      isozymes in the pathogenesis of this model. Experimental colitis was induced by
      treatment with 2.5% DSS in drinking water for 6 days. Indomethacin (a
      nonselective COX inhibitor), SC-560 (a selective COX-1 inhibitor), or celecoxib
      (a selective COX-2 inhibitor) was given PO twice daily for 6 days, during the
      first 3 or last 3 days of the experimental period. Daily treatment with 2.5% DSS
      for 6 days caused damage to the colon, with a decrease in body weight gain and
      colon length as well as an increase of myeloperoxidase (MPO) activity. All COX
      inhibitors given for 6 days significantly worsened the severity of DSS-induced
      colonic damage with increased MPO activity. The aggravation was also observed by
      SC-560 given for the first 3 days or by celecoxib given for the last 3 days. The
      expression of COX-2 mRNA in the colon was upregulated on day 3 during DSS
      treatment, with significant increase of prostaglandin E(2) PGE(2) production. The
      PGE(2) content on day 3 during DSS treatment was inhibited by both indomethacin
      and SC-560, but not by celecoxib; on day 6 it was suppressed by both indomethacin
      and celecoxib, but not SC-560. These results suggest that endogenous
      prostaglandins (PGs) afford protection against colonic ulceration, yet the COX
      isozyme responsible for the production of PGs differs depending on the stage of
      ulceration; COX-1 in the early stage and COX-2 in the late stage.

PMID- 17429721
TI  - Extended octreotide suppression test to determine hormone responsiveness of
      multiple type I gastric carcinoid tumors.
AB  - A 70-year-old man was found to have at least 12 type I gastric carcinoids and
      microcarcinoidosis. We performed an extended octreotide suppression test to
      determine if the tumors were gastrin-dependent and would likely regress after
      antrectomy. He was given an octreotide infusion at 12.5-25 mcg/h for 86 hr
      followed by depot octreotide 20 mg intramuscularly every four weeks for eight
      months. Fasting serum gastrin and chromogranin A levels were measured, and
      endoscopy with biopsies was performed before and after the infusion and at five
      months and eight months. Total RNA was extracted for quantitation of histidine
      decarboxylase mRNA using real-time PCR. Fasting serum gastrin decreased from 306
      pg/ml pretreatment to 31 pg/ml at the end of infusion and 115 pg/ml at eight
      months. Chromogranin A decreased from four to six times the upper limit of normal
      to normal. Tissue histidine decarboxylase mRNA decreased 50-fold. At eight
      months, only a few diminutive nodules were present on endoscopy. These results
      demonstrated that the carcinoid tumors in this patient were under neuroendocrine
      control and were expected to respond to antrectomy.

PMID- 17429722
TI  - Nimesulide alters cell recruitment into mitosis in murine intestinal crypts
      without influencing the cell production rate.
AB  - The use of nonsteroidal anti-inflammatory drugs (NSAIDs) that exhibit COX-2
      selectivity is associated with fewer gastrointestinal side effects than seen with
      more traditional NSAIDs. To determine whether the early effects on cell kinetics
      in the intestinal mucosal epithelium described after COX-2 selective inhibition
      are sustained following continuous therapy with these inhibitors, assessments of
      morphometry and cryptal cell proliferation in the murine small intestinal mucosa
      were made at 24 hr after treatment with indomethacin, a dual COX inhibitor (10
      mg/kg body weight intraperitoneally), nimesulide, a selective COX-2 inhibitor (15
      mg/kg body weight intraperitoneally), or vehicle. Nimesulide-treated intestine
      was elongated beyond control values, in contrast to the shorter indomethacin
      treated intestine, but anomalous villous forms were present in both treated
      groups. Both treatments induced expansion and contraction of proliferating
      compartments in the crypts in different regions of the intestine but nimesulide
      did not alter crypt cell production rates, in contrast to the down-regulation
      induced by indomethacin. These findings may provide some of the fundamental basis
      for the gut-sparing properties seen in patients treated with COX-2 selective
      inhibitors.

PMID- 17429723
TI  - Carrageenan reduces bone morphogenetic protein-4 (BMP4) and activates the
      Wnt/beta-catenin pathway in normal human colonocytes.
AB  - Carrageenans are highly sulfated polysaccharides that are widely used as food
      additives in the Western diet, in order to improve the texture of processed
      foods. Although native and degraded carrageenans induce colonic ulcerations,
      polyps, and colorectal tumors in animal models, very little is known about the
      effects of carrageenan on human colonocytes. We evaluated effects of lambda
      carrageenan (lambdaCGN) on the normal human colonocyte cell line NCM460, using a
      concentration of 1 mug/ml, about less than one tenth the average daily exposure
      to carrageenan in the Western diet. We measured secreted bone morphogenetic
      protein-4 (BMP4) in spent media and quantified its expression by quantitative RT
      PCR. Wnt-related genes were measured by an oligonucleotide array. Cellular beta
      catenin was quantified by ELISA. We found a marked decline in secreted BMP4 (P <
      0.001) following exposure of NCM460 cells to lambdaCGN for 24 hr. Quantitative RT
      PCR for BMP4 transcripts revealed 24% and 45% inhibition of expression on days 2
      and 4. cDNA gene expression array of Wnt signaling pathway target genes
      demonstrated significant changes, including 4.5-fold induction of Wnt 9A and
      suppression of Dickkopf 3 and RHOU genes. Measurement of beta-catenin by ELISA
      revealed concomitant accumulation with increases of 67.8%, 61.6%, and 73.9% on
      days 1, 2, and 4, compared to untreated controls. We conclude that treatment of
      normal human colonocytes with lambdaCGN activated the Wnt/beta-Catenin cascade
      and suppressed the expression and secretion of BMP4, inducing significant changes
      in cellular pathways that are associated with both sporadic and juvenile polyps.
      CGN may influence development of intestinal polyps in vivo by these mechanisms.

PMID- 17429724
TI  - Acute appendicitis as a rare complication after endoscopic mucosal resection.

PMID- 17429725
TI  - Solitary fibrous tumor of the cervical esophagus.

PMID- 17429726
TI  - Prospective, randomized trial comparing effect of oral versus intravenous
      pantoprazole on rebleeding after nonvariceal upper gastrointestinal bleeding: a
      pilot study.
AB  - Proton pump inhibitors (PPIs) reduce the rate of rebleeding in patients with
      nonvariceal upper GI bleed (NVGIB). Oral (PO) and intravenous (IV) pantoprazole
      are equipotent in raising gastric pH. We conducted a pilot study comparing the
      efficacy of PO vs. IV pantoprazole for reducing rebleeding after NVGIB. Patients
      with NVGIB were randomized to receive PO (80 mg BID for 3 days) or IV (80-mg IV
      bolus and 8 mg/hr infusion for 3 days) pantoprazole followed by pantoprazole, 40
      mg PO BID, for 30 days. All patients underwent endoscopy within 24 hr and
      endotherapy was applied where necessary. Twelve patients randomized to the PO and
      13 to the IV pantoprazole group were comparable in age, hematocrit, Rockall
      scores, ulcer characteristics, and endoscopic interventions. Two patients in the
      IV arm rebled and another in the IV arm developed reversible renal failure. No
      patient in the PO arm rebled, had organ failure, or had to be changed to IV
      pantoprazole. We conclude that in this pilot study, the effect of PO pantoprazole
      on 30-day rebleeding rate in patients with NVGIB was similar to that of IV
      pantoprazole.

PMID- 17429727
TI  - Gastric status and vitamin B12 levels in cardiovascular patients.
AB  - Proper absorption of vitamin B12 requires gastric corpus mucosa that functions
      appropriately and secretes intrinsic factor needed as an essential cofactor for
      the absorption of dietary vitamin B12 in the small bowel. Here we describe the
      prevalence of vitamin B12 deficiency and atrophic corpus gastritis (ACG) in
      patients with coronary heart disease. Fasting serum was obtained from patients
      who were admitted for cardiovascular diseases at the Coronary Care Unit in
      Nijmegen, the Netherlands. The status of gastric mucosa was assessed by using the
      serum levels of pepsinogens I and II, gastrin-17, and Helicobacter pylori IgG
      antibodies and analyzed over vitamin B12 level subgroups. The study population
      consisted of 376 patients (mean age, 65 years [SD, 13 years], 227 [60%] males).
      Low vitamin B12 levels (<150 pM) were detected in 28 patients (7%). Of these 28
      patients, 5 (18%) had ACG according to the biomarker assays. Altogether, another
      140 patients (37%) had vitamin B12 levels between 150 and 250 pM, of whom 10 (7%)
      had ACG. Of the remaining patients, five (2%) had ACG. Deficiency of vitamin B12
      is common among subjects with coronary heart disease. Up to 20% of these
      deficiencies are related to ACG.

PMID- 17429728
TI  - Pneumocystis jiroveci (carinii) pneumonia after infliximab therapy: a review of
      84 cases.
AB  - Anti-tumor necrosis factor-alpha therapy, infliximab, has become an established
      effective therapy for Crohn's disease and rheumatoid arthritis. However,
      infliximab has been associated with various opportunistic pathogens such as
      tuberculosis, histoplasmosis, listeriosis, aspergillosis, and Pneumocystis
      jiroveci (carinii) pneumonia. We reviewed the FDA Adverse Event Reporting System
      for cases of Pneumocystis associated with infliximab use from January 1998
      through December 2003. The database revealed 84 cases of PCP following infliximab
      therapy. Concomitant immunosuppressive medications included methotrexate,
      prednisone, azathioprine, 6-mercaptopurine, and cyclosporine. Mean time between
      infliximab infusion and onset of symptoms of pneumonia, when reported, was 21
      days (+/-18 days; n=40). Twenty-three of the 84 (27%) patients died. The use of
      infliximab is associated with PCP infection. Further, the mortality rate for
      Pneumocystis following the use of infliximab is significant. The potential for
      severe disease, mortality, and often subtle presentation of these infections
      warrant close follow-up and careful monitoring after therapy.

PMID- 17429729
TI  - Helicobacter pylori and coronary artery disease: which is the better target
      population?

PMID- 17429730
TI  - Hypercalcemic encephalopathy in a patient with hepatocellular carcinoma.
AB  - Cirrhotic patients with hepatocellular carcinoma (HCC) frequently develop hepatic
      encephalopathy. Metabolic etiology of encephalopathy is less often considered in
      these patients. Although paraneoplastic hypercalcemia may be associated with
      several malignant tumors, it has also been described in HCC [1-4], and may cause
      neurologic disturbances. We present a case of hypercalcemic encephalopathy in a
      patient with hepatic cirrhosis and underlying HCC in whom first diagnostic was
      hepatic encephalopathy.

PMID- 17429731
TI  - The microvascular thrombi of colonic tissue in ulcerative colitis.
AB  - Mucosal microvascular thrombi in rectal biopsies were observed in some ulcerative
      colitis (UC). Heparin may be effective in steroid resistant UC in some studies,
      however, the new results of meta-analysis demonstrated a non-significant effect
      of heparin in controlled clinical trials, differing markedly from observational
      studies. The objective of this study was to identify colonic microvascular
      thrombi in larger cases with UC, and analyse its possible risk factors: age,
      gender, histologic score, extent of lesions and operation or biopsy specimens,
      and assess the significance of microvascular thrombosis in patients with UC. The
      microvascular thrombi were identified by immunohistochemical staining with anti
      CD61 monoclonal antibody and Martius scarlet blue (MSB) staining in 40 colonic
      tissue samples of UC (31 biopsy specimens and nine operated cases) and 12 cases
      of normal colon tissue from operated colonic carcinoma. Logistic regression
      analysis was used to assess the relationship of age, gender, degree of histology,
      origin of the specimens, extent of lesions and microvascular thrombi examined.
      Microvascular thrombi were positive in 14 of 40 UC cases, and none in the
      controls. The presence of microvascular thrombi was related to operation
      specimens with odds ratio 11.667, P=0.0179, it might be also related to
      histologic score (OR=1.350) and extent of lesions (OR=1.619). These results
      suggest that microvascular thrombosis may be one of the important pathogenesis in
      some UC, and that the effect of anticoagulant treatment still needs to be
      assessed.

PMID- 17429732
TI  - Role of alpha-2 adrenoceptors in regulation of giant migrating contractions and
      defecation in conscious dogs.
AB  - The aim was to investigate the effects of alpha(2)-adrenoceptor antagonist
      yohimbine on colonic motility and defecation. The effects of yohimbine (0.5, 1.0,
      and 3.0 mg/kg) on colonic motility and defecation were studied in neurally intact
      dogs (N=6), dogs with extrinsic denervation of the ileocolon (N=4), and dogs with
      enterically isolated ileocolnic loops (N=5) equipped with strain gauge force
      transducers on the ileocolon. The effects of yohimbine on colonic motility and
      defecation were also studied in the presence of various antagonists (atropine,
      hexamethonium, ondansetron, FK224, and naloxone). Yohimbine evoked giant
      migrating contractions and defecation in a dose-independent manner in neurally
      intact dogs. These stimulatory effects of yohimbine were abolished by atropine
      and hexamethonium. In dogs with extrinsic denervation, yohimbine induced giant
      migrating contractions in the colon but did not stimulate defecation. In dogs
      with ileocolonic loops, yohimbine induced colonic motor complexes but not giant
      migrating contractions in the enterically isolated colon. These results indicate
      that alpha(2)-adrenoceptors in the peripheral nervous system regulate giant
      migrating contractions by controlling the release of acetylcholine, while those
      in the central nervous system must be important in the regulation of defecation.

PMID- 17429733
TI  - The serum endothelin-1 level in steatosis and NASH, and its relation with
      severity of liver fibrosis.
AB  - Endothelin-1 (ET-1) is known to play an important role in hepatic fibrosis. ET-1
      is also a mediator that is elevated in conditions such as insulin resistance,
      hyperglycemia, oxidative stress, and endothelial cell dysfunction. In this study,
      we investigated whether ET-1 has a role in determining the severity of liver
      fibrosis in NASH. Also, the relation between ALT levels, obesity, diabetes, and
      AST/ALT ratio and fibrosis and ET-1 level was sought. A total of 92 patients were
      enrolled in the study. The patients were categorized into three groups: group 1,
      patients with elevated transaminase levels who were diagnosed as NASH by liver
      biopsy (n=40); group II, patients with only hepatosteatosis determined by biopsy
      but having elevated transaminase levels (n=12); and group III, patients with
      hepatosteatosis observed by ultrasonography, having normal transaminase levels
      (n=40). The serum ET-1 level was measured by an appropriate ELISA kit for all
      patients. Mean serum ET-1 level was statistically significantly higher in the
      NASH group compared to the other two groups (15.56+/-4.63 vs 6.75+/-2.46 and
      5.74+/-2.34 micromol/L; P < 0.01). Mean serum ET-1 levels in NASH patients with
      grade I, grade II, and grade IV fibrosis were 14.06+/-0.92, 17.70+/-2.32, and
      20.40+/-1.40 micromol/L, respectively. None of the patients were identified as
      grade III fibrosis. It was found that the serum ET-1 level showed a statistically
      significant increase as fibrosis severity increased in NASH patients (P < 0.05).
      In conclusion, the serum ET-1 level is higher in NASH patients compared to
      patients having only steatosis. There appears to be a correlation between
      severity of fibrosis and serum ET-1 level in NASH patients. It has been found
      that NASH patients having a twofold increase in their ALT levels had higher ET-1
      levels and a more severe grade of fibrosis.

PMID- 17429734
TI  - The effects of rosiglitazone, metformin, and diet with exercise in nonalcoholic
      fatty liver disease.
AB  - Our aim was to evaluate effects of metformin, rosiglitazone, and diet with
      exercise in nonalcoholic fatty liver disease. Forty-seven patients (mean age,
      44+/-10 years; 17 female) whose ALT levels had been high for at least 6 months
      and with hepatosteatosis detected by liver biopsy and/or USG were enrolled in
      this study. Of these, 12 were treated with 850 mg/day metformin (group 1), 11
      with 4 mg/day rosiglitazone (group 2), and 24 with diet and exercise (group 3)
      for 1 year. ALT normalization at months 6 and 12 was accepted as treatment
      response. Liver biopsy was performed in all patients in groups 1 and 2 before
      treatment and 12 patients (4 in group 1, 8 in group 2) after treatment; but in
      group 3 it was performed only in patients who approved this procedure (12
      patients). Body mass index did not change in groups 1 and 2, but it decreased
      significantly in group 3 (30+/-3 to 28+/-2 kg/m(2)) at month 12. Treatment
      response rate was 33.3, 54.5, and 54.2% in groups 1, 2, and 3, respectively, at
      month 6. This rate was 22.2, 37.5, and 41.2 in groups 1, 2, and 3, respectively,
      at month 12. Rate of steatosis and stage of fibrosis did not change after
      treatment. Diet with exercise seems to be superior to metformin and
      rosiglitazone. Decreasing treatment response at month 12 compared to month 6 may
      be due to fluctuations of ALT levels. Treatment response should be evaluated
      histologically.

PMID- 17429735
TI  - Diagnosis and measurement of liver fibrosis by MRI in bile duct ligated rats.
AB  - The noninvasive evaluation of liver fibrosis is a major clinical goal in liver
      diseases. Our aim was to identify MRI parameters to quantify liver fibrosis in
      vivo in an animal model of liver fibrosis with slight inflammation. We evaluated
      serum hyaluronate, liver hydroxyproline, area of liver fibrosis (image analysis),
      and 1.5-T MRI in 10 sham rats and 24 bile duct ligated rats with different stages
      of liver fibrosis. Liver signal intensity (SI)/muscle SI ratio and liver
      relaxation times (rT) were measured on T1 and T2 weighted sequences at different
      echo (TE) or recovery (RT) times of MRI. Among the 66 MRI parameters tested, the
      highest correlation with the area of fibrosis was observed for rT2 (r=0.78, P <
      0.01). The area of liver fibrosis was independently predicted by five MRI
      variables (adjusted R (2)=0.78, with R (2)=0.64 for rT2 and rT1). Diagnostic
      accuracy for liver fibrosis was 100% using two variables: liver/muscle SI ratio
      on T2 at 30-ms TE and liver/muscle SI ratio on T1 at 50-ms RT. We conclude that
      in this animal model, fibrosis could be diagnosed with an accuracy of 100% using
      two MRI parameters. The quantification of liver fibrosis was very accurate either
      with only one MRI parameter (r=0.78 for rT2) or with five parameters (r=0.90) in
      this cholestatic model.

PMID- 17429736
TI  - Outcome of ERCP in the management of duct-to-duct anastomotic strictures in
      orthotopic liver transplant.
AB  - This study sought to determine the efficacy of endoscopic treatment of duct-to
      duct anastomotic stricture in orthotopic liver transplant. A retrospective chart
      and database review was carried out using procedure and diagnosis codes during
      the period of 1997-2001. One hundred ninety-eight adult patients underwent
      orthotopic liver transplantation from 1997 to 2001. Fifteen patients (age 52+/-9
      years; 60% women) with duct-to-duct anastomotic strictures were identified. They
      underwent a total of 53 endoscopic retrograde cholangiopancreatographies (ERCPs)
      and received different endoscopic treatments including biliary dilation, stent
      placement, and sphinctrerotomy. Thirteen of these patients (87%) had complete
      resolution of stricture. Of the remaining two patients, one had partial
      resolution of stricture and underwent long-term self-expanding metal stenting,
      while the other had no resolution after two ERCPs. We conclude that ERCP was
      effective in treating 87% of the duct-to-duct anastomotic strictures in this
      series.

PMID- 17429737
TI  - Levels of hepatitis B virus (HBV) replication during the nonreplicative phase:
      HBV quantification by real-time PCR in Korea.
AB  - The levels of HBV replication in the nonreplicative phase are not clear. We
      conducted this study to evaluate the levels of viral replication during the
      nonreplicative phase in chronic HBV-infected Korean patients using real-time PCR.
      A total of 125 patients were classified into three groups: inactive HBsAg
      carriers, inactive liver cirrhosis patients, and resolved chronic HBV-infected
      patients with loss of HBsAg. The real-time PCR detected HBV DNA in 112 cases
      (89.6%). The mean levels of HBV DNA were 3.84, 4.10, and 3.31 log copies/ml in
      the three groups, respectively (P <0.01). Ninety-five percent of inactive HBsAg
      carriers showed levels of HBV DNA lower than 6 x 10(4) copies/ml. In conclusion,
      we showed different levels of HBV DNA exactly in three groups during
      nonreplicative phases. We suggest that the cutoff level of HBV DNA in inactive
      HBsAg carriers should be readjusted to a lower level in future studies.

PMID- 17429739
TI  - Giant cystic colorectal liver metastasis: an unusual presentation.

PMID- 17429738
TI  - Curcumin prevents the development of dextran sulfate Sodium (DSS)-induced
      experimental colitis.
AB  - Curcumin is a phenolic natural product isolated from the rhizome of Curcuma longa
      (turmeric). We evaluated the effects of curcumin on the development of dextran
      sulfate sodium (DSS)-induced experimental colitis. BALB/c mice were fed a chow
      containing either 3.5% (wt/wt) DSS or 3.5% DSS + 2.0% (wt/wt) curcumin. The body
      weight loss was more apparent in DSS-treated mice than in DSS + curcumin-treated
      mice. The disease activity index, histological colitis score, and MPO activity
      were all significantly higher in DSS-treated mice than in DSS plus curcumin
      treated mice. Microscopically, mucosal edema, cellular infiltration, and
      epithelial disruption were much more severe in DSS-treated mice than in DSS +
      curcumin-treated mice. In DSS + curcumin-treated mice, NF-kappaB activation was
      blocked in the mucosa. In conclusion, the development of DSS-induced colitis was
      significantly attenuated by curcumin. Being a nontoxic natural dietary product,
      curcumin could be useful in treatment of IBD patients.

PMID- 17429740
TI  - Eosinophilic gastroenteritis: a review.
AB  - Eosinophilic gastroenteritis is a rare benign disease characterized by tissue
      eosinophilic infiltration that may involve several digestive tract layers. Also
      known as allergic, or eosinophilic allergic, gastroenteropathy, it usually
      involves the stomach and small intestine: rarely the colon. It may or may not be
      accompanied by higher counts of eosinophils in the peripheral blood. The main
      clinical manifestations depend on the site affected. It has been classified
      according to clinical and pathological features, and the symptoms depend on the
      patient's immunological response to several cytokines released by eosinophils.
      Because of lack of understanding of the etiology and triggering factors,
      treatment is based mainly on corticosteroids; although other drugs acting on the
      immune system have been tested, the results are not always satisfactory. This
      review focuses on the epidemiology, pathophysiology, clinical features, and
      treatment of this hitherto under-diagnosed disease.

PMID- 17429741
TI  - Reduction of protease inhibitor activity by expression of a mutant Bowman-Birk
      gene in soybean seed.
AB  - A mutant Bowman-Birk gene was created that encoded an inactive high-sulfur
      product. It was used to transform soybean line Asgrow 3237. Transformants bearing
      the mutant gene were identified by GUS expression, PCR analysis, and Southern
      analysis. The amount of steady state mRNA from the mutant gene in the transformed
      plants showed that the gene was highly expressed, but the amount of message from
      the unmodified Bowman-Birk gene did not change detectably. Proteins synthesized
      at the direction of the mutant Bowman-Birk gene accumulated in seeds of the
      transformed plants, and there was a marked decrease in the ability of extracts
      prepared from these seeds to inhibit trypsin and chymotrypsin despite the
      presence of Kunitz trypsin inhibitor. The more prevalent mRNA from the mutant
      gene was considered to out-compete message from the native genes to decrease the
      amount of active Bowman-Birk inhibitor.

PMID- 17429743
TI  - Ethanol induces secretion of oxidized proteins by pancreatic acinar cells.
AB  - The pancreas is vulnerable to ethanol toxicity, but the pathogenesis of alcoholic
      pancreatitis is not fully defined. The intracellular oxidative balance and the
      characteristics of the secretion of isolated rat pancreatic acinar cells
      stimulated with the cholecystokinin analogue cerulein were assayed after acute
      oral ethanol (4 g/kg) load. Pancreatic acinar cells from ethanol-treated rats
      showed a significant (p < 0.02) lower content of total glutathione and protein
      sulfhydryls, and higher levels of oxidized glutathione (p < 0.03),
      malondialdehyde, and protein carbonyls (p < 0.05). Ethanol-intoxicated acinar
      cells showed a lower baseline amylase output compared to controls, with the
      difference being significantly exacerbated by cerulein stimulation. After
      cerulein, the release of protein carbonyls by ethanol-treated cells was
      significantly increased, whereas that of protein sulfhydryls was significantly
      decreased. In conclusion, ethanol oxidatively damages pancreatic acinar cells;
      cerulein stimulation is followed by a lower output of amylase and by a higher
      release of oxidized proteins by pancreatic acinar cells from ethanol-treated
      rats. These findings may account for the decreased exocrine function,
      intraductular plug formation, and protein precipitation in alcoholic
      pancreatitis.

PMID- 17429742
TI  - A barley activation tagging system.
AB  - Activation tagging, as the result of random genomic insertion of either promoter
      or enhancer sequences, can produce novel, dominant mutations by over-expression
      of endogenous genes. This powerful genomics tool has been used extensively in
      dicot species such as Arabidopsis, while rice is the only cereal for which an
      equivalent system exists. In this study we describe an activation tagging system
      in barley based upon the maize Ac/Ds transposable element system. A modified Ds
      element (UbiDs) containing two maize polyubiquitin promoters, transposed in
      families derived from multiple independent UbiDs transformants and generated new
      Ds insertion events at frequencies ranging from 0% to 52% per family. The
      majority of transposed UbiDs elements activated high levels of adjacent flanking
      sequence transcription. Transposon-mediated expression was detected in all barley
      cell and tissue types analysed suggesting that this system is applicable to all
      aspects of plant development and biogenesis. In addition to transcriptional
      activation, this system is also capable of generating insertional knockout
      mutants and a UbiDs inactivated allele of the granule bound starch synthase I
      gene (waxy) was recovered that lead to reduced amylose accumulation. The recovery
      and analysis of dominant over-expression phenotypes generated by this system will
      provide a novel approach to understanding gene function in large cereal genomes
      where gene redundancy may mask conventional loss-of-function mutations.

PMID- 17429744
TI  - Interindividual differences in initial DNA repair capacity when evaluating H2O2
      induced DNA damage in extended-term cultures of human lymphocytes using the comet
      assay.
AB  - It has been suggested that extended-term cultures of human lymphocytes could be
      used as a complement to cell lines based on transformed cells when testing the
      genotoxicity of chemicals. To investigate whether the pattern of induced DNA
      damage and its subsequent repair differs significantly between cultures based on
      different blood donors, hydrogen peroxide (H(2)O(2))-induced DNA damage was
      measured in cultures from four different subjects using the comet assay. The DNA
      damage was significantly increased in all cultures after 10 min exposure to 0.25
      mmol/L H(2)O(2), and there was a significant decrease in the H(2)O(2)-induced DNA
      damage in all cultures after 30 min of DNA repair. The level of damage varied
      between the different donors, especially after the repair. Using PCR and DNA
      sequencing, exon 5 of the p53 gene was sequenced in the lymphocytes from the
      donors with the lowest and highest residual damage. No such mutation was found.
      Mouse lymphoma L5178Y cells carrying the p53 mutation in exon 5 were included as
      a reference. These cells were found to be less sensitive toward the H(2)O(2)
      induced DNA damage, and they were also found to have a rather low DNA repair
      capacity. The demonstrated variation in H(2)O(2)-induced DNA damage and DNA
      repair capacity between the cultures from the different subjects may be important
      from a risk assessment perspective, but is obviously not of decisive importance
      when it comes to the development of a routine assay for genotoxicity.

PMID- 17429745
TI  - Disrupting mitochondrial function with surfactants inhibits MA-10 Leydig cell
      steroidogenesis.
AB  - It is well established that surfactants can elicit cytotoxic effects at threshold
      concentrations by changing the permeability and solubilizing components of cell
      membranes. The purpose of this study was to characterize the relationship between
      perturbation of the mitochondrial membrane resulting from treatment with
      representative cationic, nonionic, and anionic surfactants and the extent to
      which this perturbation affects steroid formation and StAR protein expression and
      activity in MA-10 Leydig cells. The StAR protein is synthesized as an active 37
      kDa extramitochondrial form, which is processed into a 30 kDa intramitochondrial
      form after cholesterol transfer and mitochondrial import and processing. It has
      been shown in several in vitro studies that the mitochondrial electrochemical
      gradient is required for the StAR protein to transfer cholesterol to the inner
      mitochondrial membrane. Each substance that was tested produced a concentration
      dependent decrease in steroid formation in hCG-stimulated MA-10 cells. Decreases
      in progesterone production were accompanied by loss of mitochondrial membrane
      potential and by a decrease in the levels of the 30 kDa form of the StAR protein.
      However, levels of the 37 kDa form of the StAR protein did not decrease,
      indicating no effect on StAR protein expression. These results demonstrate how
      perturbation of the mitochondrial membrane by surfactants inhibits import,
      processing, and cholesterol transfer activity and underscore the importance of
      including sensitive assays that evaluate mitochondrial function when screening
      for potential effects on steroidogenesis with in vitro test systems.

PMID- 17429746
TI  - Localization and transcription of a retrotransposon-derived element on the maize
      B chromosome.
AB  - Dispensable chromosomes in addition to the normal complement in diverse taxa are
      called B chromosomes. The maize B chromosome is discernible in mitotic chromosome
      spreads as a small compact chromosome composed mainly of heterochromatin.
      Although much of this chromosome consists of repetitive elements common to the A
      chromosomes, several sequences specific to the B chromosome have been identified.
      In the work described here we used the sequence from a B-specific RAPD (random
      amplification of polymorphic DNA) marker, pBGBM18.2, to isolate another DNA
      element, StarkB, present in many copies on the B chromosome. StarkB was mapped to
      the third and fourth blocks of distal heterochromatin using translocation
      breakpoints and fluorescent in-situ hybridization (FISH). Sequence analysis
      revealed that StarkB is composed of fragments from the A genome as well as B
      specific sequences. The StarkB element is much larger than the other B-specific
      elements and is not present in large tandem arrays. Different copies of StarkB
      varied by small insertions, deletions, and duplications as well as single
      nucleotide polymorphisms. Reverse transcriptase PCR showed that portions of the
      StarkB element are expressed. Using the LTR divergence of retroelements
      interrupting the B-specific sequences, the minimum age of the StarkB repeat array
      and, by inference, of the B chromosome, was estimated to be 2 million years.

PMID- 17429748
TI  - Bioaccumulation and translocation of metals in the natural vegetation growing on
      fly ash lagoons: a field study from Santaldih thermal power plant, West Bengal,
      India.
AB  - A field study was conducted in the fly ash lagoons of Santandih Thermal Power
      Plant located in West Bengal (India) to find out total, EDTA and DTPA extractable
      metals in fly ash and their bioaccumulation in root and shoot portion of the
      naturally growing vegetation. Fly ash sample has alkaline pH and low
      conductivity. The concentration of total Cu, Zn, Pb and Ni were found higher than
      weathered fly ash and natural soil, where as Co, Cd and Cr were found traces.
      Five dominant vegetation namely, Typha latifolia, Fimbristylis dichotoma,
      Amaranthus defluxes, Saccharum spontaenum and Cynodon dactylon were collected in
      the winter months (November-December). Bioaccumulation of metals in root and
      shoot portions were found varied significantly among the species, but all
      concentration were found within toxic limits. Correlation between total, DTPA and
      EDTA extractable metals viz. root and shoot metals concentration were studied.
      Translocation factor (TF) for Cu, Zn and Ni were found less than unity, indicates
      that these metals are immobilized in the root part of the plants. Metals like Mn
      have TF greater than unity. The study infers that natural vegetation removed Mn
      by phytoextraction mechanisms (TF > 1), while other metals like Zn, Cu, Pb and Ni
      were removed by rhizofiltration mechanisms (TF < 1). The field study revealed
      that T. latifolia and S. spontaenum plants could be used for bioremediation of
      fly ash lagoon.

PMID- 17429749
TI  - A tribute to Hemming Virgin (1918-2005), a Swedish pioneer in plant photobiology.
AB  - We present here a tribute to Hemming Ivar Virgin (October 19, 1918-October 19,
      2005), a pioneer in Swedish plant photobiology, developer of a University, and an
      outstanding educator.

PMID- 17429747
TI  - Use of cross-species in-situ hybridization (ZOO-FISH) to assess chromosome
      abnormalities in day-6 in-vivo- or in-vitro-produced sheep embryos.
AB  - Causes of chromosomal differences such as mosaicism between embryos developed in
      vivo and in vitro may be resolved using animal models to compare embryos
      generated in vivo with those generated by different production systems. The aims
      of this study were: (1) to test a ZOO-FISH approach (using bovine painting
      probes) to detect abnormal chromosome make-up in the sheep embryo model, and (2)
      to examine the extent of chromosome deviation in sheep embryos derived in vivo
      and in vitro. Cytogenetic analysis was performed on day 6 in-vivo and in-vitro
      derived sheep embryos using commercially available bovine chromosome painting
      probes for sex chromosomes X-Y and autosomes 1-29. A total of 8631 interphase and
      metaphase nuclei were analyzed from 49 in-vitro-derived and 51 in-vivo-derived
      embryos. The extent of deviation from normal ovine chromosome make-up was higher
      (p < 0.05) in in-vitro-produced embryos relative to in-vivo-derived embryos
      (65.3% vs. 19.6% respectively) mainly due to diploid-polyploid mosaicism.
      Polyploid cells ranged from 3n to 8 n with tetraploids most predominant among non
      diploid cells. The proportions of polyploid cells per mixoploid embryo in in
      vitro-produced embryos ranged from 1.4% to 30.3%, in contrast to less than 10%
      among the in-vivo-derived embryos. It was concluded that in-vitro-derived embryos
      are vulnerable to ploidy change compared to their in-vivo counterparts. The
      application of ZOO-FISH to domestic animal embryos is an effective approach to
      study the chromosome complement of species for which DNA probes are unavailable.

PMID- 17429750
TI  - Thylakoid membrane landscape in the sixties: a tribute to Andrew Benson.
AB  - Prior to the 1960s, the model for the molecular structure of cell membranes
      consisted of a lipid bilayer held in place by a thin film of electrostatically
      associated protein stretched over the bilayer surface: (the Danielli-Davson
      Robertson "unit membrane" model). Andrew Benson, an expert in the lipids of
      chloroplast thylakoid membranes, questioned the relevance of the unit membrane
      model for biological membranes, especially for thylakoid membranes, instead of
      emphasizing evidence in favour of hydrophobic interactions of membrane lipids
      within complementary hydrophobic regions of membrane-spanning proteins. With
      Elliot Weier, Benson postulated a remarkable subunit lipoprotein monolayer model
      for thylakoids. Following the advent of freeze fracture microscopy and the fluid
      lipid-protein mosaic model by Singer and Nicolson, the subunits, membrane
      spanning integral proteins, span a dynamic lipid bilayer. Now that high
      resolution X-ray structures of photosystems I and II are being revealed, the
      seminal contribution of Andrew Benson can be appreciated.

PMID- 17429752
TI  - A tale of naming a photosynthetic bacterium.

PMID- 17429751
TI  - Oxidation state changes of the Mn4Ca cluster in photosystem II.
AB  - A detailed electronic structure of the Mn4Ca cluster is required before two key
      questions for understanding the mechanism of photosynthetic water oxidation can
      be addressed. They are whether all four oxidizing equivalents necessary to
      oxidize water to O2 accumulate on the four Mn ions of the oxygen-evolving
      complex, or do some ligand-centered oxidations take place before the formation
      and release of O2 during the S3 --> [S4] --> S0 transition, and what are the
      oxidation state assignments for the Mn during S-state advancement. X-ray
      absorption and emission spectroscopy of Mn, including the newly introduced
      resonant inelastic X-ray scattering spectroscopy have been used to address these
      questions. The present state of understanding of the electronic structure and
      oxidation state changes of the Mn4Ca cluster in all the S-states, particularly in
      the S2 to S3 transition, derived from these techniques is described in this
      review.

PMID- 17429753
TI  - Deprivation of pantothenic acid elicits a movement disorder and azoospermia in a
      mouse model of pantothenate kinase-associated neurodegeneration.
AB  - We asked whether a movement disorder could be elicited by deprivation of
      pantothenic acid (PA; vitamin B5), the substrate for the enzyme pantothenate
      kinase 2 (PANK2), which is deficient in the inherited neurological disorder PKAN
      (pantothenate kinase-associated neurodegeneration formerly called Hallervorden
      Spatz syndrome). This study was undertaken because mice made null for Pank2
      failed to show the neurological manifestations of the human disease. Wild-type
      and Pank2 mutant mice were fed pantothenic acid-deficient diets and were
      monitored for general health, fertility and movement compared with animals on
      control diets over time. Mice of both genotypes on PA-deficient diets exhibited
      poor grooming, greying of fur and decreased body weight. With PA deprivation,
      wild-type mice manifested azoospermia (a phenotype also seen in Pank2 mice) as
      well as a movement disorder with a low-lying pelvis and slow steps. Rear limbs
      appeared to drag and occasionally extended into unnatural postures for 16-17 s
      duration, possibly indicative of dystonia. Movement disruption probably also
      occurs in PA-deprived Pank2 mutant mice, but they died precipitously before
      undergoing detailed analysis. Remarkably, restoration of dietary PA led to
      recovery of general health and grooming, weight gain, reversal of the movement
      disorder, and reappearance of mature sperm within 4 weeks. This study confirms
      the primacy of PA metabolism in the mechanism of disease in PKAN. PA deprivation
      provides a useful phenocopy for PKAN and allows us to test pharmacological and
      other interventional strategies in the treatment of this devastating disease.

PMID- 17429754
TI  - Reduced adverse effects with an accelerated dobutamine stress protocol compared
      with the conventional protocol: a prospective, randomized myocardial perfusion
      scintigraphy study.
AB  - BACKGROUND: Dobutamine (Dob) stress myocardial perfusion scintigraphy (MPS) has
      been shown to have diagnostic and prognostic value. However, the protocol
      recommended for Dob-MPS is long and frequently associated with adverse effects.
      We sought to compare two stress protocols with Dob in patients undergoing MPS.
      METHODS AND RESULTS: 168 patients undergoing Dob-MPS were consecutively studied.
      Two protocols were randomly used: progressive doses of Dob (steps of 10
      microg/kg/min at 3-min intervals) up to 40 microg/kg/min, aiming at reaching a
      minimum of 85% of the age-corrected maximal predicted heart rate (HR), possibly
      adding atropine to maximal Dob dose in case HR was not achieved (conventional
      protocol) or progressive doses of Dob aiming at the same HR, but adding atropine
      at the end of the first stage (accelerated protocol). We compared age, gender,
      coronary risk factors, history of MI or revascularization, Dob infusion and total
      stress times, maximal HR, percentage of maximal predicted HR, rate-pressure
      product, ST changes, MPS scores and incidence of adverse effects. In the 84
      patients who underwent the accelerated protocol, the incidence of adverse effects
      was reduced (34.5%) compared to the conventional protocol (54.8%; P < 0.05), as
      well as Dob infusion duration (508 +/- 130 vs. 715 +/- 142 sec; P < 0.001). We
      did not observe significant differences between the groups as to age, gender,
      clinical aspects, maximal HR, percentage of achieved maximal HR, rate-pressure
      product, ST changes and perfusion scores. CONCLUSION: Early administration of
      atropine makes stress faster and reduces incidence of adverse effects, without
      reducing efficacy towards achieving the proposed goals.

PMID- 17429755
TI  - Gadolinium-enhanced magnetic resonance imaging for detection and quantification
      of fibrosis in human myocardium in vitro.
AB  - BACKGROUND: The availability of a non-invasive test to detect and quantify
      interstitial and replacement fibrosis would be a useful advance for evaluation of
      cardiac therapies that could prevent fibrosis progression. There is an
      established role for magnetic resonance imaging (MRI) in the assessment of
      replacement fibrosis (when fibrosis replaces myocytes), but the potential for
      assessment of interstitial fibrosis (when amount of fibrosis increases between
      myocytes) has not been evaluated. METHODS: A novel in vitro MRI technique was
      developed for comparison of gadodiamide contrast distribution volume as a measure
      of both kinds of myocardial fibrosis, with histologically determined myocardial
      collagen volume fraction, the current gold standard for quantification of
      myocardial fibrosis. Eight samples of human myocardium were obtained postmortem
      and a fast spin-echo sequence (3 Tesla) with non-slice selective inversion pulse
      performed before and after immersion in a gadodiamide saline solution for
      determination of the gadodiamide partition coefficient. T1 values were calculated
      from the inversion recovery signal curves. The same samples were fixed in
      formalin, and collagen volume fraction was determined by the picrosirius red
      method using a semi-automated, polarized, digital microscopy system. RESULTS:
      Both gadodiamide distribution volumes as well as CVF values were significantly
      different in normal myocardium versus interstitial fibrosis (P = 0.001), and
      normal versus replacement fibrosis (P = 0.015). Moreover, there was a significant
      positive correlation between the two methods, across all three histological
      categories of myocardial fibrosis (r = 0.73; P = 0.017). CONCLUSION: These
      findings indicate an expanded potential for gadodiamide enhanced MRI as a novel,
      non-invasive alternative to histological evaluation, for the quantification of
      both interstitial and replacement myocardial fibrosis.

PMID- 17429756
TI  - The PARC-AALA trial: carotid artery intima media thickness revisited.

PMID- 17429757
TI  - Production and fungitoxic activity of Sch 642305, a secondary metabolite of
      Penicillium canescens.
AB  - Production of fungitoxic extrolites was evaluated in culture filtrates of several
      isolates belonging to Penicillium canescens and P. janczewskii that showed some
      extent of inhibitory activity against the plant pathogenic fungus Rhizoctonia
      solani. In addition to griseofulvin and dechlorogriseofulvin that are already
      known in these species, curvulinic acid, previously unreported in Penicillium,
      was produced by all isolates assayed. Another extrolite recently characterized
      from a P. verrucosum strain by the name of Sch 642305 was detected in 5 isolates
      of P. canescens only. The purified compound completely inhibited mycelial growth
      of isolates of Rhizoctonia solani and other plant pathogenic fungi in vitro. The
      role of this extrolite as a possible biochemical determinant of antagonism toward
      plant pathogenic fungi, and implications concerning chemotaxonomy are discussed.

PMID- 17429758
TI  - Analysis of DNA damage induced by aflatoxin B1 in Dunkin-Hartley guinea pigs.
AB  - Aflatoxin B1 (AFB1) is among the most potent naturally occurring carcinogens and
      classified as a group I carcinogen. Since the ingestion of aflatoxin-contaminated
      food is associated with several liver diseases, the aim of the present study was
      to evaluate the effect of 2, 20, and 200 ppb of AFB1 on DNA damage in peripheral
      blood lymphocytes and liver cells in Dunkin-Hartley guinea pigs. The animals were
      divided into four groups according to the given diet. After the treatment the
      lymphocytes and liver cells were isolated and DNA damage determined by Comet
      assay. The levels of DNA damage in lymphocytes were higher animals treated with
      200 ppb of AFB1-enriched diet (P = 0.02). In the liver cells there were a
      relationship between the levels of DNA damage and the consumption of AFB1 in all
      studied groups. These results suggest that Comet assay performed on lymphocytes
      is a valuable genotoxic marker for high levels of exposure to AFB1 in guinea pig.
      Additionally our results indicate that the exposure to this toxin increases
      significantly and increases the level of DNA damage in liver cells, which is a
      key step on liver cancer development. We also suggest that the Comet assay is an
      useful tool for monitoring the genotoxicity of AFB1 in liver.

PMID- 17429759
TI  - Genetic diversity of Rhynchosporium secalis in Tunisia as revealed by pathotype,
      AFLP, and microsatellite analyses.
AB  - Genetic variability among 122 Rhynchosporium secalis isolates collected from
      barley in three regions of Tunisia was investigated using host differentials,
      amplified fragment length polymorphism (AFLP), and microsatellite markers. The
      isolates were collected from a widely grown scald-susceptible barley cultivar
      Rihane and a range of local landrace cultivars in geographically distinct regions
      with different agroclimatic conditions. Pathotypic diversity (the proportion of
      unique pathotypes) was high in R. secalis populations from the high (100%
      diversity), moderate (95%), and low (100%) rainfall areas of Tunisia, and from
      both Rihane (which is the sole variety grown in the high rainfall region) and
      local landraces (which predominate in the low rainfall area). This may reflect a
      general adaptability for aggressiveness and suggests that the widely grown
      cultivar Rihane has exerted little or no selection pressure on the pathogen
      population since its release in 1983. Genotypic diversity (GD), defined as the
      probability that two individuals taken at random had different genotypes, was
      high for populations from Rihane, local landraces, and different agro-ecological
      zones (GD = 0.96-0.99). There was low genetic differentiation among pathogen
      populations from different host populations (G(ST) < or = 0.08, theta < or =
      0.12) and agro-ecological zones (G(ST) < or = 0.05, theta < or = 0.04), which may
      be partly explained by gene flow due to the movement of infected stubble around
      the country. There was no correlation (r = 0.06, P = 0.39) between virulence
      phenotype and AFLP haplotype. A phenetic tree revealed groups with low bootstrap
      values that did not reflect the grouping of isolates based on host, pathotype, or
      agro-ecological region. The implications of these findings for R. secalis
      evolutionary potential and scald-resistance breeding in Tunisia are discussed.

PMID- 17429760
TI  - Adult weight gain and central obesity in women with and without a family history
      of breast cancer: a case control study.
AB  - Adult weight gain and central obesity can increase breast cancer risk. We
      determined the prevalence of adult weight gain and central obesity amongst women
      with a family history (FH) as compared to women with a population risk to
      determine whether adiposity could contribute to their increased risk. Adult
      weight gain, waist and waist:hip ratio (WHR) were determined amongst 475 women
      (aged 20-60 years) attending a regional FH breast cancer risk clinic, compared to
      312 age matched women at population risk. Patterns of adult weight gain did not
      differ between women with and without a FH of breast cancer. The majority of
      weight gain occurred between the ages of 20 and 40 in both groups. Mean (sd)
      weight gain for women aged >40 years with a FH was 8.9 (10.3) kg compared to 9.1
      (10.6) kg for controls (p = 0.85). Women with a FH had a significantly greater
      waist and WHR than controls. Mean (sd) waist was 83.7 (13) cm compared to 81.6
      (11.3) cm for controls (p < 0.01). Mean (sd) WHR was 0.82 (0.1) compared to 0.80
      (0.1) for controls (p < 0.01). FH of breast cancer was an independent predictor
      of having a WHR of >0.85; odds ratio (95% CI) = 1.42 (1.01-2.01) (p = 0.044).
      Significant weight gain between the ages of 20 and 40 and the prevalence of
      central obesity amongst FH women suggest the need for weight management within FH
      clinics.

PMID- 17429761
TI  - [Psychometric evaluation of the German version of the "Consultation and
      Relational Empathy" (CARE) measure at the example of cancer patients].
AB  - The patient-reported assessment of physician empathy can be indicated for outcome
      research, at interventions and in medical practice. The aim of this investigation
      is the evaluation of the psychometric properties of the German version of the
      "Consultation and Relational Empathy" (CARE) measure on the example of inpatient
      cancer patients (N = 326). The one-dimensional structure of the instrument can be
      replicated by a confirmatorical factor analysis. Hypothesis-consistent
      relationships to different patient and physician factors as well as to socio
      demographic and illness-particular features of the patients can be shown. In
      medical practice the CARE-scale can be used by the physician e. g. as a time
      economic feedback instrument for the evaluation of strengths and weaknesses of
      their empathic behaviour, as a personal behaviour checklist within a consultation
      and/or as a checklist to determine patient preferences before/during a
      consultation.

PMID- 17429762
TI  - [Convergence of the Adult Attachment Prototype Rating (AAPR) with different self
      assessment measures of attachment characteristics].
AB  - Within the past years there has been a controversial discussion on the adequate
      assessment of attachment (observational vs. self report). Based upon data from a
      student sample (N = 65), the aim of this study was to determine the convergence
      between the interview-based AAPR (Adult Attachment Prototype Rating) and eleven
      different self-report measures to assess attachment characteristics. With the
      exception of the AAPR self-description (AAPR-SB), no self report measure reached
      a statistically significant convergence with the AAPR categories of the
      attachment styles (secure, ambivalent, avoidant). With respect to attachment
      security, the highest correlations were found between the interview-based rating
      and the Relationship Specific Attachment Scales (version related to the
      attachment figure "mother", BBE, r = 0.46), as well as the Bielefeld Partnership
      Expectations Questionnaire (BFPE, r = 0.38). Combining these two measures,
      approximately 30 % of the variance of the AAPR-attachment security measure could
      be explained. Besides the specificity of the methods, the results indicate
      divergences of attachment measures related to time (e. g. childhood vs. present)
      or attachment figures (e. g. mother vs. partner) indicating the need to specify
      attachment related constructs in studies with adults.

PMID- 17429763
TI  - [Problem identification and attitudes towards obesity prevention: a
      representative survey investigation].
AB  - Although obesity prevention is increasingly being implemented, attitudes towards
      obesity prevention in the population are largely unclear. In a representative
      population-based survey, n = 1,000 individuals were interviewed about their
      agreement with specific preventive measures and level of problem identification,
      using computer-assisted telephone interviewing. The results show substantial
      agreement with obesity prevention, especially with obesity prevention in children
      and with information-based prevention. There was less agreement with legal
      measures. Support of prevention was low in men, young people, and in those with
      low income. Information deficits regarding the definition, prevalence, and
      chronicity of obesity were identified. Based on strong overall agreement with
      obesity prevention, addressing specific information deficits could enhance
      understanding of obesity and help sustainable implementation of preventive
      measures.

PMID- 17429764
TI  - Hyaluronan-based antiadhesive agents in abdominal surgery: applications, results,
      and mechanisms of action.
AB  - Postsurgical intra-abdominal adhesions cause significant morbidity and mortality,
      with small bowel obstruction being the most common complication. The urge to
      prevent adhesion formation has resulted in multiple experimental and clinical
      trials and the development of numerous antiadhesive agents. Through the years,
      hyaluronan-based antiadhesives have proved to be successful in the reduction of
      adhesion formation. Despite the obvious effectiveness of hyaluronan, there is
      still much debate on its clinical use and mechanisms of action. Various
      hyaluronan-containing products have been introduced and withdrawn from the
      market. The application of hyaluronan in combination with meshes for hernia
      repair appears to be a promising concept. Not all different applications of
      hyaluronan are well known and its use in patients with a malignancy or abdominal
      infection remains controversial. Here an overview is given on the effects of
      hyaluronan-based antiadhesive agents in abdominal surgery, its use in infectious
      conditions, and its oncologic repercussions. The most important mechanism of
      action appears to be the mechanical separation of damaged peritoneal surfaces.
      However, the biological effects of hyaluronan, such as modulation of cell
      proliferation and peritoneal biology, might also be of influence.

PMID- 17429765
TI  - The role of fibrin sealants in hepatic surgery.
AB  - The repair of all tissue disruption begins with hemostasis and tissue sealing.
      Fibrin sealant is a concentrated mix of the factors required for the body to
      initiate this process. By applying this mixture directly to the site of injury,
      clotting and wound healing can be facilitated. Studies have demonstrated that
      fibrin sealant is effective in controlling bleeding and inducing tissue sealing
      in many organs. It is particularly useful in hepatobiliary surgery due to the
      soft nature of liver parenchyma and its propensity to bleed and leak bile. This
      chapter will discuss the basic science foundation of fibrin sealants and their
      applications in hepatic surgery.

PMID- 17429766
TI  - Abdominal dermolipectomy in laparotomy with stoma surgery: case report.
AB  - In cases of morbid obesity, excessive soft tissue in the abdomen forms an apron
      like deformity called panniculus because of rapid weight loss due to cancer. In
      laparotomy with stoma aimed at cancer resection, obesity is reported as a major
      risk factor of stoma complications, one of the most frequent of which is
      necrosis. In one patient in whom a laparotomy was performed through a midline
      incision, the authors also carried out an abdominal dermolipectomy aimed at
      reducing distortion of the abdominal wall in relation to the stoma. This
      procedure provided two important advantages for stoma surgery, stability, and
      better postoperative care by the patient.

PMID- 17429767
TI  - Perioperative thermal insulation.
AB  - Perioperative hypothermia remains a common problem during anesthesia and surgery.
      Unfortunately, the implementation of new minimally invasive surgical procedures
      has not lead to a reduction of this problem. Heat losses from the skin can be
      reduced by thermal insulation to avoid perioperative hypothermia. However, only a
      small amount of information is available regarding the physical properties of
      insulating materials used in the Operating Room (OR). Therefore, several
      materials using validated manikins were tested. Heat loss from the surface of the
      manikin can be described as:"Q = h . DeltaT . A" where Q = heat flux, h = heat
      exchange coefficient, DeltaT = temperature gradient between the environment and
      surface, and A = covered area. Heat flux per unit area and surface temperature
      were measured with calibrated heat flux transducers. Environmental temperature
      was measured using a thermoanemometer. The temperature gradient between the
      surface and environment (DeltaT) was varied and "h" was determined by linear
      regression analysis as the slope of "DeltaT" versus heat flux per unit area. The
      reciprocal of the heat exchange coefficient defines the insulation. The
      insulation values of the materials varied between 0.01 Clo (plastic bag) to 2.79
      Clo (2 layers of a hospital duvet). Given the range of insulating materials
      available for outdoor activities, significant improvement in insulation of
      patients in the OR is both possible and desirable.

PMID- 17429768
TI  - Novel applications of Dermabond (2-octyl -cyanoacrylate) in cardiothoracic
      surgery.
AB  - Dermabond (Ethicon Inc., Somerville, NJ, USA) is a cyanoacrylate adhesive
      normally indicated for skin wound closure. This study describes the emergency use
      of this adhesive to control bleeding close to coronary anastomoses in exceptional
      cases. Dermabond was used in 17 patients who underwent cardiac surgery during an
      eight-month period, where other haemostatic interventions were unsuitable. It was
      applied for haemorrhage in 15 patients and control air leaks in two of the
      patients. Haemostasis was successful with Dermabond alone in 11 patients; the
      remaining four required additional interventions. It effectively controlled
      haemorrhage from ventricular pacing wires, vascular sling holes, peri-anastomotic
      bleeding, and epicardial tears. The adhesive was not placed directly on any graft
      because of embolic risk. In the two patients with visible air leaks, it was
      successfully used. No patient events were recorded as a result of haemorrhage and
      no reported toxicity. Dermabond may be indicated in circumstances in which
      haemostasis with traditional methods has failed or is inappropriate. A need for
      further high-quality objective research exists on the effectiveness and long-term
      safety of 2-octyl cyanoacrylate in cardiac surgery.

PMID- 17429769
TI  - Gastrointestinal staple line reinforcement.
AB  - Gastrointestinal resections and anastomoses are commonly performed using stapling
      devices in a wide range of open and laparoscopic procedures. Whether they are
      hand-sewn or stapled, anastomoses have an associated leak rate that can impart
      significant morbidity or mortality to a procedure. In addition, bleeding from
      staple lines can cause additional complications. Staple line reinforcement is one
      intervention that has been postulated to reduce both the leak rate and associated
      bleeding risk. This can be accomplished with either material applied exogenously
      to the staple line, as in an engineered absorbable biomaterial, or it may use a
      material - either absorbable or nonabsorbable - that is incorporated into the
      staple line. A number of reinforcements are currently available but all add time
      and cost to the procedures in which they are used. However, preventing the
      complications associated with leak and hemorrhage from staple lines may justify
      the added cost of these devices. A review of the available published literature
      was performed to review the current data pertaining to the reinforcement of
      living tissue and anastomoses with these various reinforcements available to
      surgeons.

PMID- 17429770
TI  - Endoscopic full-thickness gastric resection using a flexible stapler device.
AB  - Endoluminal resection in the gastrointestinal tract is limited to resection of
      the lamina mucosa and lamina submucosa. The integrity of the gastric wall,
      represented by the lamina muscularis propria, must be maintained, because no safe
      endoscopic methods of ensuring adequate closure of the gastric wall are currently
      available. With the flexible stapling system SurgAssist (Power Medical
      Interventions ([Power Medical Interventions Deutschland GmbH, Hamburg, Germany]),
      for the first time, a stapling device is available that can be introduced
      transorally into the gastric area together with a gastroscope. After performing
      appropriate animal experiments, full-thickness inverted resection of a tumorous
      section of the gastric wall was done in two patients with early gastric
      adenocarcinoma. In both patients, the authors were able to resect full-thickness
      sections of the gastric wall with a diameter of approximately 4 x 4 cm. A
      gastroscope was used for control of the resected areas in the stomach; one
      patient required endoscopic hemostasis. The further postoperative course was
      uneventful in both patients. The method presented herein offers, for the first
      time, an exclusively transoral, surgical procedure for full-thickness resection
      of the gastric wall. In addition to early gastric adenocarcinoma with incipient
      infiltration of the submucosa, possible indications for this procedure include
      gastrointestinal stromal tumors.

PMID- 17429771
TI  - Solid tumor resection by use of a highly sensitive micromagnetic needle detection
      system.
AB  - The objective of this study was to evaluate the efficiency of tumor detection in
      parenchymal organs and their resection by use of a micromagnetic needle detection
      system (MNDS). A micromagnetic needle (maximum magnetic flux density = 120 mT)
      and a micromagnetic needle-setting device were used. An in vitro laboratory study
      with a gumball within gelatin representing a tumor was conducted to calculate
      detection rates and to measure the time required for resection by MNDS. An animal
      study with the cervical lymph nodes of pigs representing tumors was conducted to
      measure the time required for lymph node resection. The removal rate of the
      target lymph node was 100% with MNDS. Results show that MNDS may be useful for
      tumor resection in the presence of air and for the resection of tumors that are
      difficult to detect by ultrasonography.

PMID- 17429772
TI  - Current role of laparoscopic surgery for liver malignancies.
AB  - The use of laparoscopic surgery in managing liver malignancies has been developed
      only recently because of the complexity of liver surgery. Diagnostic laparoscopy
      is useful in staging liver malignancies before resection. The need for
      laparoscopic staging of colorectal liver metastasis has diminished as a result of
      better imaging technology such as positron emission tomography (PET). Laparoscopy
      still plays an important role in the staging of hepatocellular carcinoma because
      of the high incidences of multifocal tumors and venous invasion. Recently,
      laparoscopic liver resection was possible with the availability of new
      instruments that allow relatively bloodless liver transection. Small series have
      reported a conversion rate of 10% to 20%, and the complication rate and
      transfusion rate appeared to be comparable with open surgery in a few
      retrospective case-control studies. Limited data also suggest that oncological
      clearance and long-term outcome were not compromised. However, the role of
      laparoscopic liver resection is confined mainly to wedge or segmental resection
      of anterior segments of the right lobe and left lateral segments. Although
      successful laparoscopic hemihepatectomy and resections of segments VII and VIII
      have been reported at the time of this writing, these should be attempted only in
      centers that have already acquired wide experience with laparoscopic liver
      resection. Another application of laparoscopic surgery for the management of
      liver malignancies is laparoscopic radiofrequency ablation, which is gaining
      popularity because of its well-documented safety and efficacy. With further
      developments in technology, that laparoscopic surgery will have a greater impact
      on the management of liver malignancies is foreseeable in the near future.

PMID- 17429773
TI  - Laparoscopic excision of leiomyomas in the esophageal and gastric wall.
AB  - Laparoscopic minimally invasive procedures have become feasible and safe
      alternatives to open surgery in the management of esophageal and gastric
      leiomyomas. There are two major indications for the surgical management of these
      benign tumors: the presence of symptoms and the need for histopathologic
      confirmation if the biological behavior is unclear. The approach of choice for
      leiomyomas located in the very distal esophagus or gastroesophageal junction is
      the laparoscopic enucleation of the tumor. For the resection of gastric
      leiomyomas, three surgical procedures are primarily performed: the laparoscopic
      wedge resection without gastrotomy for tumors of the anterior gastric wall,
      lesser/greater curvature, and fundus; the laparoscopic wedge resection with
      gastrotomy for tumors of the posterior gastric wall ("transgastric approach");
      and the laparoscopic intragastric resection for tumors of the posterior gastric
      wall ("intragastric approach"). This chapter summarizes these minimally invasive
      techniques and provides an update of the most recent clinical data that is
      available.

PMID- 17429774
TI  - Anti-reflux pouch-esophagostomy after total gastrectomy.
AB  - The most prominent and severe complication after a total gastrectomy is severe
      reflux esophagitis. We have developed a procedure involving jejunal pouch
      esophagostomy to avoid such postoperative reflux. The novel procedure reported
      here initially involves folding a jejunal segment of approximately 35 cm in
      length. A side-to-side jejuno-jejunostomy at the anti-mesenteric side was then
      affected using a 100-mm linear stapler. This resulted in a jejunal pouch, 10 cm
      in length, and a 7-cm apical section of unstapled jejunal loop. Finally, an
      esophago-jejuno end-to-side anastomosis (pouch-esophagostomy) was formed at the
      right anterior wall of the apical bridge using a circular stapler. We have
      therefore introduced a "partial posterior fundoplication"-like wrapping technique
      to the standard gastrectomy using the apical bridge of the jejunal pouch. Only a
      little postoperative reflux was revealed by barium meal testing - even in the
      Trendelenburg's position - in patients treated with the described anti-reflux
      anastomosis procedure. Jejunal pouch reconstruction with partial posterior
      wrapping is a useful procedural addition for minimizing reflux esophagitis
      following a total gastrectomy.

PMID- 17429775
TI  - A simple and inexpensive method for laparoscopic appendectomy.
AB  - Laparoscopic appendectomy (LA) was introduced into clinical practice by Kurt Semm
      in 1983. Since then, a number of methods for performing LA have emerged in the
      literature. However, the majority of these modifications require costly
      equipment. In this short technical chapter, we describe a very simple and
      inexpensive method of performing this procedure without resorting to any
      additional expensive paraphernalia.

PMID- 17429776
TI  - Aggressive surgical treatment of retroperitoneal sarcoma: long-term experience of
      a single institution.
AB  - Surgery is the main modality in the therapy of retroperitoneal soft-tissue
      sarcomas (RSTS). A retrospective study was undertaken to evaluate the results of
      aggressive surgical treatment in a series of patients of primary and recurrent
      retroperitoneal sarcomas. A review of 166 consecutive patients with RSTS operated
      on at the Institute of Oncology in Ljubljana from 1975 through 2005 were
      reviewed. A total of 269 operations were performed on 166 patients. The five- and
      ten-year survival rates of patients with localized sarcoma were 52% and 38%,
      respectively. Factors that influenced the survival were distant metastases, tumor
      grade, and type of resection. The patients with R0 resections had a five-year
      survival rate of 75% and a ten-year survival rate of 65%; the respective rates
      for the patients with R1 resections were 25% and 7% (p < 0.00001). When only R0
      resection was considered, referral status (primary, residual, recurrent RSTS)
      influenced survival (p = 0.004). The quality of initial surgery is a crucial
      prognostic factor to predicting survival in patients with RSTS. Complete surgical
      resection without microscopic residuum and contamination is likely to offer the
      best chances for long-term survival. Unless no other treatment modalities are
      available, aggressive surgery for recurrent sarcoma is recommended.

PMID- 17429777
TI  - Selective tissue elevation by pressure injection (STEP) facilitates endoscopic
      mucosal resection (EMR).
AB  - Endoscopic mucosal resection and endoscopic submucosal dissection have become
      more common in treatment of flat superficial tumors of the gastrointestinal
      tract. Submucosal injection is used to try to avoid complications and improve the
      technical feasibility of the procedure. However, the method has its limitations,
      particularly when treating extensive flat tumors in the colon. The water-jet
      dissector has already demonstrated its capacity for selective cutting with the
      dissection of parenchymatous. This chapter addresses a new indication,
      transmucosal mucosal elevation, together with first clinical results. After
      carrying out animal experiments into the physical properties using animal
      preparations and freshly resected human specimens from operations, our work group
      investigated and compared the applicability of the procedure using different
      carrier fluids. Six test substances-hydroxyethyl starch (HES), Gelafusal,
      Infukoll, Glucose 50 und isotonic saline solution-were injected into six
      anesthetized pigs; the height of the submucosal fluid cushion created by the
      injection was measured endosonographically over a period of 45 minutes.
      Endoscopic mucosal resection was subsequently carried out, and the resected
      specimen together with the area it was taken from were assessed histologically.
      Using commercially available NaCl cartridges, applied by the way of
      endocapillaries, 18 lesions were elevated in a series of 12 patients and
      subsequently resected endoscopically. All investigated substances could be
      applied without difficulty using the Helix HydroJet (Erbe Elektromedizin GmbH,
      Waldhornle-Str., Tubingen, Germany). The plasma expanders (HES and Gelafundin 4%,
      B. Braun Melsungen AG, Melsungen, Germany) produced longer lasting fluid cushions
      than the isotonic solutions. Mucosal resections could be carried out in all cases
      with all of the solutions. Histological investigation confirmed the selective
      nature of the fluid accumulation in the submucosal tissue, which spared the
      lamina mucosae and lamina muscularis propria. The first clinical applications
      were successful. The technique of selective fluid accumulation in the submucosa
      by pressure injection, selective tissue elevation by pressure injection (STEP),
      presented herein for the first time in a clinical setting, makes it easier to
      carry out endoscopic mucosal resections and expands the use of this technique to
      treatment of extended lesions. The manufacturer has announced his intention of
      combining this technology with an IT-knife, so further improvements can be
      expected.

PMID- 17429778
TI  - Innovations in ventral hernia repair.
AB  - There is a renewed interest in the surgical repair of ventral hernias due to new
      meshes and new techniques to use these meshes. The standard of care for ventral
      hernia repair, the Rives-Stoppa repair, is now more commonly done in the USA.
      Originally, only polypropylene mesh (PPM) or polyester meshes were available for
      this technique and they had to be placed extraperitoneally. With development of
      the laparoscopic approach for ventral hernia repair using expanded
      polytetrafluoroethylene (ePTFE), newer coated meshes for intraperitoneal
      placement were developed. Companies have also combined polypropylene mesh (PPM)
      and polytetrafluoroethylene (PTFE) into a unique mesh and numerous biologic
      meshes are being introduced. All of these meshes have led to several new methods
      for ventral hernia repair (including parastomal hernia) and in those cases where
      mesh is not indicated, one non-mesh repair, the components separation, has
      received renewed attention.

PMID- 17429779
TI  - Meshes in hernia repair.
AB  - The search for safe and effective means of herniorrhaphies has been ongoing for
      more than a century. Evidence strongly supports tension-free hernia repairs in
      most patients, which result in a 50% reduction in a ten-year cumulative rate of
      hernia recurrence compared with tissue repairs. Polypropylene mesh revolutionized
      the field approximately 50 years ago; however, limitations of traditional
      polypropylene mesh have fueled the research and development of other prosthetic
      and biologic mesh products. Newer polyester and expanded polytetrafluoroethylene
      (ePTFE) products are designed to improve pliability and reduce adhesiogenic
      potential. Combination meshes capitalize on the ideal properties of biomaterials
      by strategically positioning particular mesh surfaces to selectively impede or
      promote tissue ingrowth. The most recent improvement in mesh products is the
      introduction of "lightweight" meshes. In response to mounting evidence that the
      traditional formulations of polypropylene meshes are over-engineered, lightweight
      meshes were designed with less polypropylene per surface area. Future research
      may prove that most meshes used currently are "mechanical overkill," which may
      lead to a widespread use of lightweight meshes to provide a durable repair,
      minimize chronic mesh-related discomfort, and improve the overall quality of life
      of hernia patients.

PMID- 17429780
TI  - Hernioplasty with Surgisis Inguinal Hernia Matrix (IHM).
AB  - Although at present nonabsorbable meshes are the preferred material for tension
      free hernioplasty, some problems with their use are still to be addressed (i.e.,
      chronic pain and infections). To address these disadvantages, a collagen-based
      material, the porcine small intestinal submucosa mesh, has recently been
      developed for hernia repair. The technique to use this material in performing an
      hernioplasty is described. A preshaped Surgisis Inguinal Hernia Matrix (IHM) is
      fashioned as appropriate, with a slit 2 cm from its inferior edge to accommodate
      the spermatic cord, placed for at least 10 min into a dish with room-temperature
      normosaline to be rehydrated and then transferred to the already prepared and
      dissected inguinal region. After drawing its tails around the cord, the mesh is
      sutured to the inguinal ligament with a continuous suture of PDS II 2/0, starting
      from the pubic tubercle laterally up to the deep orifice. The fixation of the
      mesh to the internal oblique abdominal muscle and the rectus sheath is
      accomplished with interrupted stitches. An extra stitch is placed between the two
      tails to close the new deep orifice. We conclude that an hernioplasty using
      Surgisis IHM is feasible with promising results.

PMID- 17429781
TI  - Laparoscopic treatment of bowel endometriosis.
AB  - The most common site of extragenital endometriosis is the intestinal tract, which
      accounts for approximately 80% of all extragenital endometriosis. The symptoms of
      intestinal endometriosis are crampy pain, flatulence, painful tenesmus, hyper
      peristalsis, progressive constipation, diarrhea alternating with constipation,
      and occasionally rectal bleeding. As endometriosis in this location often
      undergoes fibrotic changes, it can be resistant to hormonal therapy, which makes
      surgical therapy the only option for many women. Until recently, laparoscopic
      treatment of bowel endometriosis was thought to be impossible. Development of
      several safe and effective techniques for laparoscopic treatment of intestinal
      endometriosis has made such treatment possible. In this chapter, the authors
      describe five proven techniques for treatment of intestinal endometriosis:
      shaving, disk excision, anterior rectal wall excision, segmental resection, and
      appendectomy.

PMID- 17429782
TI  - Microwave endometrial ablation: development and clinical application.
AB  - Heavy menstrual bleeding is a common problem. Hysterectomy has been the standard
      treatment for women with heavy menstrual bleeding who have not responded to
      medical treatment. Minimally invasive procedures to destroy the lining of the
      uterus (the endometrium) are alternatives to hysterectomy. They involve
      destroying the endometrium using lasers, radiofrequency waves, electrocautery,
      microwaves, heated saline, or a heated balloon. Microwave endometrial ablation
      (MEA) is one of these minimally invasive procedures. In this Chapter, use of
      microwave MEA in the management of heavy menstrual bleeding is described. MEA was
      developed in Bath, UK in the mid 1990s. MEA is a second-generation method of EA,
      which involves the use of microwaves at a fixed frequency of 9.2 GHz to destroy
      the endometrial lining. Initial results for MEA were encouraging, with active
      treatment times of less than three minutes and high satisfaction rates. Recent
      studies also showed an equivalent outcome with regards to patients' satisfaction
      and health-related quality-of-life issues. The procedure, indications,
      contraindications, principles of operation, potential risks, results, and patient
      satisfaction is described herein.

PMID- 17429783
TI  - Cutaneous uretero-ureterostomy: a technique of urinary diversion for high-risk
      patients with bladder cancer.
AB  - A simplified technique of cutaneous ureterostomy (CU) is presented for the
      treatment of high-risk bladder cancer patients. From 1968 to 2003, 2118
      cystectomies with CU were performed for bladder cancer patients with uremic
      manifestations. The mean age was 67.4 +/- 27.3; 1206 patients were men and 912
      were women. Cutaneous uretero-ureterostomy (CUU) was performed by three methods:
      (a) one ureter was brought across the midline and anastomosed end-to-side to the
      other ureter (end-to-side uretero-ureterostomy, ESUU); (b) the two ureters were
      placed side by side in a double-barrel fashion (double-barrel ureterostomy, DBU);
      or (c) the two distal ureteric ends were anastomosed together before fixation to
      the skin (side-to-side uretero-ureterostomy, SSUU). Selection of the technique
      depended on ureteric length and girth. No complications specific to CUU have
      occurred. Serum creatinine was normalized and intravenous pyelogram (IVP) showed
      improvement of obstructive manifestations and renal function. Ureterostomy
      stenosis was more common in ESUU than in DBU and SSUU; it responded to
      dilatation. This simple and easy procedure is shown to have a low rate of
      operative and postoperative complications and is indicated for high-risk patients
      with bladder cancer.

PMID- 17429784
TI  - Compact extracorporeal circulation: reducing the surface of cardiopulmonary
      bypass to improve outcomes.
AB  - We have introduced a number of modifications to minimize the deleterious effects
      of cardiopulmonary bypass (CPB) by reducing the surface of the extracorporeal
      circulation (ECC), the length of the ECC circuit, the contact surface of the
      oxygenator, and the volume of priming solution, in addition to employing
      biocompatible systems and isolation of excess blood volumes of venous reservoirs
      in transfusion bags very early in CPB. Encouraged by the results of our initial
      "Compact ECC," we have decided to improve it by implementing other techniques
      such as controlled hemodilution of the patient by reducing the diameter of ECC
      venous tubing (from 1/2 in. to 3/8 in.), limiting contact surface of the
      oxygenator and venous reservoir, positioning the oxygenator and venous reservoir
      at the level of the patient's shoulder, and employing venous cannulae adapted to
      vacuum assisted venous drainage (VAVD) to replace venous drainage by gravity. The
      purpose of this study is to evaluate postoperative outcomes of Compact ECC. Three
      groups of patients undergoing coronary artery bypass graft (CABG) are compared.
      Our new Compact ECC shows improved outcomes through reduced postoperative
      ventilation time, blood loss, intensive care stay, need for blood transfusion,
      and levels of lactate dehydrogenase despite the patients' pathologies and
      surgeries being more complex.

PMID- 17429785
TI  - Varicose vein surgery and endovenous laser therapy.
AB  - Varicose veins are a widespread problem, and are encountered by various medical
      specialists. Symptoms can appear from mild, such as tiredness of the legs, to
      severe chronic ulcers. Varicose veins are generally caused by the reflux of an
      incompetent saphenofemoral junction and long saphenous vein. In the presence of
      reflux, the treatment should be directed at the ablation of the hydrostatic
      forces of the reflux. Conventional surgical treatment consists of a high ligation
      of the saphenofemoral junction and stripping of the saphenous vein. In the era of
      minimally invasive surgery, various endovenous techniques have been developed,
      including endovenous laser therapy. This technique is relatively cheap and can be
      performed under only local anesthesia. During endovenous laser therapy, energy is
      delivered to the vein wall, causing it to shrink and eventually occlude.
      Currently, the mechanisms of action involved in laser treatment are not fully
      understood. Clinical studies have shown occlusion rates to be very competitive to
      conventional high ligation and stripping and superior cosmetics. Complications
      may include mild to moderate pain, ecchymosis, induration, hematoma, and
      phlebitis. All of these are generally self-limiting. In the challenge of finding
      the correct balance between a low incidence of varicose vein recurrence and
      complications and optimal cosmetic results, endovenous laser therapy is a
      promising modality. However, controlled studies that assess the effectiveness of
      endovenous laser therapy in comparison to saphenofemoral ligation with saphenous
      vein stripping are crucial before considering endovenous laser therapy as the new
      standard treatment.

PMID- 17429786
TI  - Preventing venous thromboembolism in cardiology and cardiac surgery.
AB  - Venous thromboembolism (VTE) has proven to be one of the major causes for
      increasing morbidity among general medical and surgical patients. VTE may have a
      major role after cardiac surgery by increasing morbidity related to hospital
      stay, economic burden, discharge planning, complications associated with
      anticoagulation therapy, and mortality when it ends as a fatal pulmonary embolism
      (PE). However, patients who undergo cardiac procedures or surgeries pose unique
      challenges in prevention and treatment of VTE. Clinical diagnosis is always
      difficult in these patients due to non-specific symptoms or because the patient
      is asymptomatic. Among the cardiology and cardiac surgery population, thrombosis
      risk appears to be inherent as a result of multiple co-morbidities as well as
      direct trauma to the vasculature. Prevention of VTE by prophylactic measures
      remains the most economical and effective method in current clinical practice.
      However, many modalities used for VTE prophylaxis have been restricted to the
      general surgical orthopedic population and can be difficult to apply, especially
      in patients following cardiac surgery.

PMID- 17429787
TI  - Multimodality treatment including parietal pleurectomy as a possible therapeutic
      procedure for malignant pleural effusion.
AB  - Long-term control of malignant pleural effusion is an important goal of therapy
      in patients with pleural dissemination. The authors have carried out limited
      operations combined with parietal pleurectomy (PL) for non-small cell lung cancer
      patients with pleural dissemination, based on the hypothesis that the most
      effective target area for controlling malignant pleural effusion is the parietal
      pleura. In our 25 years of experience, 54 patients with pleural dissemination (26
      also had malignant pleural effusion) have undergone this surgical treatment. The
      operative procedures used for resection of lung parenchyma were partial resection
      in 25 patients, lobectomy in 24, bilobectomy in two, segmentectomy in two, and no
      parenchymal resection (PL only) in one. Postoperative intrapleural chemotherapy
      and systemic chemotherapy (2-4 cycles) also were applied in 43 patients. The
      pathological stages were IIIB in 44 patients and IV in ten. The overall three-,
      five-, and ten-year survival rates were 29.0%, 15.0%, and 7.5%, respectively.
      Twenty patients survived for more than two years. Recurrent malignant pleural
      effusion developed in only two of 30 patients whose recurrent patterns could be
      clearly identified. Although this was not a clinical randomized comparative
      study, multimodality treatment that included the use of PL appears to be a useful
      option for treatment of this disease in appropriately selected patients.

PMID- 17429788
TI  - Liberal indications for minimally invasive oxford unicondylar arthroplasty
      provide rapid functional recovery and pain relief.
AB  - The Oxford unicompartmental knee arthroplasty (UKA) was recently approved for
      implantation in America. Recovery was evaluated and the efficacy of a
      musculoskeletal hospital was addressed for an initial group of patients who
      underwent medial compartment UKA with the Oxford device. Between October 2004 and
      December 2005, 142 medial UKAs were performed in 125 patients and included 11
      simultaneous and six staged bilateral UKA procedures, and one simultaneous
      UKA/TKA procedure. The patients' ages averaged 62 (range: 41-87) years, weight 90
      kg, and body mass index (BMI) 31.6 kg/m(2). Sixty-one UKAs were performed in
      obese patients (BMI >32). The length of stay averaged 1.3 days. In 121 (97%)
      cases, patients were discharged directly to home. In 23 (18%) cases, home health
      physical therapy was used. Outpatient physical therapy was used in 95 (76%)
      cases. Only four (3%) patients required a skilled nursing or post-discharge
      rehabilitation stay. Five reoperations were required: one revision to TKA for
      tibial plateau fracture, one revision to TKA for tibial loosening, one radical
      debridement and staged reimplantation of primary TKA for sepsis, and two
      arthroscopic procedures (one retained cement, and one synovitis). The average arc
      of motion at initial six-week follow up was 116 degrees , with 56% of knees
      having greater than 120 degrees and 82% more than 110 degrees . Absent, or only
      mild, pain was reported in 85% of knees. Seventy-five percent of patients had
      good or excellent Knee Society scores by six weeks postoperatively. UKA provides
      excellent early function and pain relief with rapid recovery when performed at a
      specialty musculoskeletal hospital. Early discharge appears to be safe and does
      not transfer the burden of care to other facilities or home health rehabilitation
      services.

PMID- 17429789
TI  - Early experience with a new total knee implant: maximizing range of motion and
      function with gender-specific sizing.
AB  - Patients considering total knee arthroplasty (TKA) now have higher expectations
      of performance including long-term implant survival and a rapid return of normal
      function. While modern implant systems have many sizes available, implant fit -
      especially in women - is often imperfect. The ability to achieve outstanding
      outcomes has many factors, requiring excellent implant fit, alignment, stability,
      range of motion, and kinematics, as well as long-lasting bearing surfaces and
      durable fixation. We present the initial two years of experience of 668
      consecutive cemented total knee arthroplasties using an implant and bearing
      surface specifically designed to address these issues. The Triathlon TKA uses
      anthropomorphic sizing, taking into account the gender-specific variable aspect
      ratio for a better fit. Modified posterior femoral condylar geometry coupled with
      a rotary arc polyethylene design allows for flexion greater than 150 degrees
      while rotating 20 degrees internally and externally both in flexion and
      extension. The X3 polyethylene insert has demonstrated superior wear
      characteristics. Early outcomes revealed mean Knee Society pain and function
      scores, improving from a preoperative total score of 78 to a postoperative score
      of 182. Patients exhibited a rapid return of knee motion from a mean preoperative
      flexion of 102 degrees to 116 degrees at 6 weeks, 124 degrees at 3 months, and
      128 degrees at 1 year. Whereas long-term results cannot be predicted, no early
      failures or serious complications were encountered. A prospective long-term
      outcome study of this cohort is underway.

PMID- 17429790
TI  - Modular calcar replacement prosthesis with strengthened taper junction in total
      hip arthroplasty.
AB  - Whereas femoral component modularity allows the surgeon to address a variety of
      femoral defects in complex total hip arthroplasty (THA), breakage of modular
      stems is a known complication that typically occurs at the taper junction. In
      response, a proprietary process of taper roller-hardening that increases taper
      strength by a factor of 3.5 was introduced in 1999. The authors reviewed a
      consecutive series of patients by a single surgeon who underwent cementless
      revision or difficult primary THA with a taper roller-hardened modular calcar
      replacement prosthesis, and have the potential for a minimum of two-year follow
      up. In 116 patients, 123 hips were involved. Two surgeries were primary, 101 were
      revision/conversion, 18 were for reimplantation after treatment of infection, and
      two were intramedullary total femur constructs, one of which was a reimplantation
      after sepsis. The patients' ages at surgery averaged 71 years, and BMIs averaged
      28.12 kg/m2. Nine of the patients, all with single hip involvement, were lost to
      contact. Twenty-one patients, three of whom had bilateral hip involvement,
      expired during the follow-up period with implant outcome known. Follow up in the
      patients who survived averaged 44 (range: 18-78) months. Six femoral components
      have been revised: two (1.6%) due to recurrent sepsis, three (2.4%) due to
      sepsis, one (0.8%) from periprosthetic fracture, and none from septic loosening
      or component breakage. Survivorship with aseptic loosening as the end-point was
      100%. In this series, roller-hardening appears to improve the durability of the
      tapered junction. No roller-hardened modular calcar devices have failed due to
      component breakage. However, their use is not recommended in the totally
      deficient proximal femur, as fatigue breaks of distally fixed monoblock
      extensively coated stems have been reported. Caution is advised when potting or
      anchoring any stem in the femoral diaphysis without reconstituting proximal bone
      stock and support.

PMID- 17429791
TI  - A lateralized tapered titanium cementless femoral component does not increase
      thigh or trochanteric pain.
AB  - Increased femoral component lateralization has been reported to recreate femoral
      offset accurately, and should provide better function. Concerns exist that
      negative effects may occur such as increased thigh pain, trochanteric bursitis,
      and loosening. The current study aims to examine whether a lateralized femoral
      component design is associated with increase in thigh pain, trochanteric pain, or
      implant failure when used to recreate hip soft tissue balance and stability. The
      authors reviewed 98 total hip arthroplasties (THA) using the Mallory-Head Porous
      femoral component. Group 1 had 49 consecutive THA performed before the
      lateralized stem was available. Group 2 had 49 consecutive THA in which
      lateralization was deemed necessary, based upon preoperative templating and
      intraoperative soft tissue balancing. Follow up averaged 46 and 38 months,
      respectively. No stems failed. Group 1 had three dislocations and Group 2 had
      none with increased offset. Six (12%) patients in Groups 1 and 3 (6%) patients in
      Group 2 had trochanteric pain (p<0.05). Three (6%) patients had moderate thigh
      pain in Group 1 and none in Group 2. Significantly less trochanteric and thigh
      pain was observed in those patients in whom a lateralized stem was deemed
      necessary. The use of a lateralized stem improves the accuracy of hip soft tissue
      reconstruction and does not increase thigh pain, trochanteric pain, or loosening.
      Accurate soft tissue reconstruction may decrease trochanteric and thigh pain and
      improve function following THA.

PMID- 17429792
TI  - Proximal opening-wedge osteotomy of the first metatarsal for correction of hallux
      valgus.
AB  - Osteotomy of the proximal metatarsal in combination with a distal soft tissue
      procedure for the correction of moderate to severe hallux valgus deformity is
      commonly performed. All described techniques have complications such as non-union
      and malunion, and many are extremely technically demanding. The purpose of this
      study is to review the results of a novel technique for the correction of hallux
      valgus, an opening-wedge osteotomy of the proximal first metatarsal with plate
      fixation. A review was performed of the results of 23 patients who underwent
      correction of hallux valgus with proximal metatarsal opening-wedge osteotomy, in
      combination with a distal soft tissue procedure and exostectomy, if indicated.
      All osteotomies were secured with plate fixation on the medial side. Indications
      for surgery included a painful bunion for greater than one year and the failure
      of nonoperative treatment. Mean corrections of 15 degrees and 7 degrees were
      achieved for the hallux valgus and 1-2 intermetatarsal angles, respectively. Four
      complications occurred, including one wound dehiscence, two incidences of
      drifting of the hallux valgus angle, and one delayed union. We find the opening
      wedge osteotomy of the proximal first metatarsal to be a technically
      straightforward procedure for correcting moderate to severe hallux valgus. The
      correction obtained is comparable to other described techniques with a
      complication rate equal to or lower than most published data at this time.

PMID- 17429793
TI  - Minimally invasive thoracolumbar costotransversectomy and corpectomy via a dual
      tube technique: evaluation in a cadaver model.
AB  - Minimally invasive surgery (MIS) is a promising new tool in the treatment of a
      variety of spinal disorders. MIS laminectomy techniques provide an effective
      means of achieving lumbar decompression. MIS corpectomy techniques have not been
      described. If feasible, such a technique would be optimal in the treatment of
      spinal metastatic disease, where traditional open techniques can result in a
      significant burden to a compromised patient. In this study, we explored the
      feasibility of a dual-tube minimally invasive thoracic corpectomy approach in a
      cadaver model. A minimally invasive thoracolumbar costotransversectomy and
      corpectomy were perfumed in eight adult cadavers. A dual-tube technique was used
      to perform a costotransversectomy followed by a corpectomy on one side, and
      through the opposite tube a transpedicular approach on the contralateral side.
      Pre- and postoperative CT scans of all cadavers were obtained to measure the
      cross-sectional area of the vertebral bodies in each specimen via a CT
      workstation. Reconstruction of the anterior column was attempted in some cadavers
      using polymethylmethacrylate (PMMA) cement. A successful costotransversectomy and
      corpectomy were completed in each cadaver. A percutaneous delivery system was
      successful in allowing an anterior column reconstruction using PMMA as a strut
      graft in selected cadavers. We demonstrated that a dual-tube MIS approach to
      thoracic corpectomy is technically feasible. Additionally, spinal stabilization
      can be achieved via percutaneous PMMA administration. This approach may provide a
      minimally invasive option in the treatment of select spinal metastases.

PMID- 17429794
TI  - Cerebral aneurysms: conventional microsurgical technique and endovascular method.
AB  - Recent advances in neurosurgery and interventional neuroradiology have brought us
      a new aspect in the treatment of cerebral aneurysms. The present series provides
      a balanced overview of the treatment of aneurysms in surgical clipping and coil
      embolization. Between January 2004 and March 2006, a total of 119 consecutive
      patients with cerebral aneurysms underwent endovascular embolization or surgical
      clipping. Of these, 79 patients suffered an aneurysmal subarachnoid hemorrhage
      (SAH), whereas the remaining 40 patients had nonruptured cerebral aneurysms. Of
      the 32 surgically treated patients, 25 (78.1%) achieved a favorable outcome. Of
      the 47 patients who underwent endovascular embolization, 38 (80.9%) achieved a
      favorable outcome. No significant difference was observed regarding the
      proportion of favorable outcomes between the two treatment modalities. Four
      patients (5.5%) who underwent endovascular embolization required re-treatments
      but no re-treatments were needed in the surgically treated patients. Of the 40
      cases with nonruptured aneurysms, 12 (30%) were treated using surgical clipping,
      whereas 28 (70%) underwent endovascular embolization. The complication rates of
      the two treatment modalities demonstrated no significant difference. A combined
      microsurgical-endovascular team approach is thus considered to provide the most
      effective means to achieve favorable outcomes for patients with cerebral
      aneurysms. A case-by-case evaluation based on the individual characteristics of
      each aneurysm is therefore considered to be essential.

PMID- 17429795
TI  - Intraoperative MRI: technology, systems, and application to pediatric brain
      tumors.
AB  - Intraoperative magnetic resonance imaging (MRI) is a revolutionary technology
      that provides real-time assessment of surgical goals for the neurosurgeon. This
      technology has rapidly evolved over the past 15 years and currently is used for a
      wide variety of pathologies. These include gliomas, pituitary adenomas,
      epileptogenic foci, and complex hydrocephalus. Early generations of similar
      systems were bulky, tedious, and had marginal image quality. The next generation
      of systems provided improved image quality, easier surgical access, the ability
      to incorporate advanced imaging modalities, and integrated neuronavigation. This
      chapter reviews the intraoperative MRI technology, the various systems currently
      available, and the application of this technology to pediatric brain tumors.
      Continued refinements in the design of these systems will likely make them
      standard of care in the near future.

PMID- 17429796
TI  - Multi-axial mechanical stimulation of tissue engineered cartilage: review.
AB  - The development of tissue engineered cartilage is a promising new approach for
      the repair of damaged or diseased tissue. Since it has proven difficult to
      generate cartilaginous tissue with properties similar to that of native articular
      cartilage, several studies have used mechanical stimuli as a means to improve the
      quantity and quality of the developed tissue. In this study, we have investigated
      the effect of multi-axial loading applied during in vitro tissue formation to
      better reflect the physiological forces that chondrocytes are subjected to in
      vivo. Dynamic combined compression-shear stimulation (5% compression and 5% shear
      strain amplitudes) increased both collagen and proteoglycan synthesis (76 +/- 8%
      and 73 +/- 5%, respectively) over the static (unstimulated) controls. When this
      multi-axial loading condition was applied to the chondrocyte cultures over a four
      week period, there were significant improvements in both extracellular matrix
      (ECM) accumulation and the mechanical properties of the in vitro-formed tissue (3
      fold increase in compressive modulus and 1.75-fold increase in shear modulus).
      Stimulated tissues were also significantly thinner than the static controls (19%
      reduction) suggesting that there was a degree of ECM consolidation as a result of
      long-term multi-axial loading. This study demonstrated that stimulation by multi
      axial forces can improve the quality of the in vitro-formed tissue, but
      additional studies are required to further optimize the conditions to favour
      improved biochemical and mechanical properties of the developed tissue.

PMID- 17429797
TI  - Detection of chromosomal abnormalities, congenital abnormalities and transfusion
      syndrome in twins.
AB  - OBJECTIVE: To evaluate the outcome of screening for structural malformations in
      twins and the outcome of screening for twin-twin transfusion syndrome (TTTS)
      among monochorionic twins through a number of ultrasound scans from 12 weeks'
      gestation. METHODS: Enrolled into this prospective multicenter observational
      study were women with twin pregnancies diagnosed before 14 + 6 gestational weeks.
      The monochorionic pregnancies were scanned every second week until 23 weeks in
      order to rule out early TTTS. All pregnancies had an anomaly scan in week 19 and
      fetal echocardiography in week 21 that was performed by specialists in fetal
      echocardiography. Zygosity was determined by DNA analysis in all twin pairs with
      the same sex. RESULTS: Among the 495 pregnancies the prenatal detection rate for
      severe structural abnormalities including chromosomal aneuploidies was 83% by the
      combination of a first-trimester nuchal translucency scan and the anomaly scan in
      week 19. The incidence of severe structural abnormalities was 2.6% and two-thirds
      of these anomalies were cardiac. There was no significant difference between the
      incidence in monozygotic and dizygotic twins, nor between twins conceived
      naturally or those conceived by assisted reproduction. The incidence of TTTS was
      23% from 12 weeks until delivery, and all those monochorionic twin pregnancies
      that miscarried had signs of TTTS. CONCLUSION: Twin pregnancies have an increased
      risk of congenital malformations and one out of four monochorionic pregnancies
      develops TTTS. Ultrasound screening to assess chorionicity and follow-up of
      monochorionic pregnancies to detect signs of TTTS, as well as malformation
      screening, are therefore essential in the antenatal care of twin pregnancies.

PMID- 17429798
TI  - Citrinin and endosulfan induced maternal toxicity in pregnant Wistar rats:
      pathomorphological study.
AB  - Dietary exposures to environmental food pollutants such as mycotoxin(s) or
      pesticide(s) have gained immense significance due to their adverse effects on
      production and reproduction in animal and human populations. The present
      investigation was conducted to evaluate the maternal toxicity of citrinin (CIT)
      and endosulfan administered per os either alone or in combination in pregnant
      rats during gestational days 6-20. CIT (group I, 10 mg kg(-1) feed, through diet)
      and endosulfan (group II, 1 mg kg(-1) body weight, by oral intubation) when
      administered either alone or in combination (group III) in Wistar rats caused
      clinical signs of toxicity and pathomorphological changes in all the toxin
      treated groups, the severity being more pronounced in the combination treatment
      compared with that observed in the control (group IV). The rate of fetal
      resorptions was highest (22.22%) in the combination treatment followed by
      endosulfan (16.48%) and CIT (12.50%) treatment groups compared with the control
      group (3.86%). The histopathological changes such as engorged vasculature,
      vacuolar degeneration and karyomegaly in liver; congestion, tubular degeneration
      and cast formation in kidneys; vascular changes and hemosiderosis in uterus and
      lymphocytic depletion and apoptosis in the lymphoid organs were recorded in the
      animals of the toxin treated groups. The lesions were consistent and more severe
      in the combination treatment group compared with the individual treatment groups,
      suggesting an additive interaction of CIT and endosulfan in inducing maternal
      toxicity in Wistar rats.

PMID- 17429799
TI  - Application of in vivo microdialysis for studying the efficacy of protective
      preparations against sulfur mustard penetrating the skin.
AB  - Subcutaneous microdialysis was employed for monitoring thiodiglycol (2,2'
      thiodiethanol, TDG) levels with the aim of characterizing the transdermal
      penetration of topically applied liquid sulfur mustard (2,2'-dichlorodiethyl
      sulfide, SM) in rats. TDG levels, evaluated in 20 min dialysates collected over a
      6 h sampling period, were plotted against time after pooling. Linear correlation
      was identified between the SM dose and the mean areas under the 0-60 min or the
      whole curve (AUC(0-60) and AUC, respectively) as well as mean peak concentrations
      (C(max)) in the range of 1.0-3.0 microl applied volume (7.2-21.7 nmol).A
      commercially available barrier cream, a perfluoropolyether oil and a vaseline
      based ointment containing zinc oxide were subsequently tested as topical
      protectants. Each preparation was layered on the skin surface prior to the
      application of 2.0 microl SM. The evaluation of the efficacy of the preparations
      was based on obtained AUC(0-60), AUC and C(max) values. A statistical comparison
      of these parameters with those obtained when 2.0 microl SM was applied without
      pretreatment indicated that the barrier cream and the perfluoropolyether oil
      significantly (P < 0.01) reduced the amount of penetrating SM within the sampling
      period. In addition, the perfluoropolyether oil almost completely prevented the
      penetration of SM for 20 min. Pretreatment with the ointment did not prove to be
      an effective countermeasure as its administration resulted in no significant
      reduction in AUC(0-60), AUC and C(max) values.

PMID- 17429800
TI  - Toxicogenomics: a pivotal piece in the puzzle of toxicological research.
AB  - Toxicogenomics, resulting from the merge of conventional toxicology with
      functional genomics, being the scientific field studying the complex interactions
      between the cellular genome, toxic agents in the environment, organ dysfunction
      and disease state. When an organism is exposed to a toxic agent the cells respond
      by altering the pattern of gene expression. Genes are transcribed into mRNA,
      which in turn is translated into proteins that serve in a variety of cellular
      functions. Toxicogenomics through microarray technology, offers large-scale
      detection and quantification of mRNA transcripts, related to alterations in mRNA
      stability or gene regulation. This may prove advantageous in toxicological
      research. In the present review, the applications of toxicogenomics, especially
      to mechanistic and predictive toxicology are reported. The limitations arising
      from the use of this technology are also discussed. Additionally, a brief report
      of other approaches, using other -omic technologies (proteomics and metabonomics)
      that overcome limitations and give global information related to toxicity, is
      included.

PMID- 17429801
TI  - Resveratrol prevents fibrosis, NF-kappaB activation and TGF-beta increases
      induced by chronic CCl4 treatment in rats.
AB  - Resveratrol is a nonflavonoid polyphenol with antioxidant, anticancer and
      antiinflammatory properties. Moreover, it has been reported that this compound
      inhibits NF-kappaB, which regulates the transcription of several genes including
      cytokines such as the profibrogenic TGF-beta. The aim of this work was to
      evaluate the pharmacological effects of resveratrol on CCl(4)-induced cirrhosis
      in the rat. Four groups were formed: the control group that received the vehicles
      only; the CCl(4) group that received the toxin (0.4 g kg(-1), i.p., three times a
      week, for 8 weeks); the CCl(4) plus resveratrol (10 mg kg(-1), daily) group; and
      the resveratrol alone group. Alanine aminotransferase, alkaline phosphatase and
      bilirubins were increased by CCl(4), but resveratrol afforded some degree of
      protection. Glycogen was decreased markedly by CCl(4) and resveratrol prevented
      almost completely this effect. No antioxidant effect of resveratrol was observed.
      One of the most prominent effects was on fibrosis which increased near 5-fold
      (hydroxyproline) in the CCl(4) group; resveratrol preserved the content of
      collagen. These results were corroborated by histopathology. To elucidate the
      antifibrogenic mechanism of resveratrol, the activation of NF-kappaB and the
      production of TGF-beta were measured; in both cases CCl(4) increased them and
      resveratrol abolished them; however, changes in NF-kappaB were modest and did not
      reach statistical significance, while the increase in TGF-beta was about three
      fold and resveratrol decreased it under control values. Together, the present
      results indicate that resveratrol possesses a strong antifibrogenic effect at
      least in the CCl(4) model of cirrhosis. Moreover, the action mechanism is
      probably associated with its ability to reduce NF-kappaB activation and TGF-beta
      content.

PMID- 17429802
TI  - Influence of alpha-tocopherol, propolis and piperine on therapeutic potential of
      tiferron against beryllium induced toxic manifestations.
AB  - The therapeutic potential of the chelator tiferron (sodium-4,5-dihydroxy-1,3
      benzene disulphonate; 300 mg kg(-1), i.p.) and adjuvants, i.e. alpha-tocopherol
      (25 mg kg(-1), p.o.), propolis (a honey-bee hive product; 200 mg kg(-1), p.o.)
      and piperine (10 mg kg(-1), p.o.) were evaluated individually and in combination
      against beryllium induced biochemical alterations and oxidative stress
      consequences. Female albino rats were exposed to beryllium nitrate (1 mg kg(-1),
      i.p.) daily for 28 days followed by treatment with the above mentioned
      therapeutic agents for 5 consecutive days. Administration of beryllium altered
      blood biochemical variables with significant depletion in hemoglobin, blood
      sugar, total serum protein, albumin and significant enhancement in the release of
      serum transaminases. A significantly increased lipid peroxidation and a decreased
      level of glutathione after beryllium exposure indicated oxidative stress in the
      liver and kidney. Beryllium exposure decreased total protein and glycogen
      contents, whereas triglycerides and cholesterol increased significantly in liver
      and kidney. Individual administration of all the four compounds showed
      significant therapeutic potential in reverse of some of the biochemical
      parameters mentioned above. Furthermore, the combination of tiferron with alpha
      tocopherol, propolis or piperine, respectively, could reverse all the variables
      significantly more towards the control. None of the test compounds showed any
      significant change in choleretic activity (bile flow and bile solids), indicating
      that these compounds had no adverse effects at these dose levels. It was
      concluded that all the combinations of tiferron and adjuvants played a beneficial
      role in reducing beryllium induced systemic toxicity at relatively lower doses
      and the combination of tiferron and propolis showed a more pronounced therapeutic
      potential.

PMID- 17429803
TI  - All-dry synthesis and coating of methacrylic acid copolymers for controlled
      release.
AB  - Initiated chemical vapor deposition (iCVD) is presented as an all-dry synthesis
      and coating method for applying methacrylic acid copolymers as pH-responsive
      controlled release layers. iCVD combines the strengths of liquid-phase chemical
      synthesis with a precision solvent-free chemical vapor deposition environment.
      Copolymers of methacrylic acid and ethyl acrylate were confirmed by a systematic
      shift in the carbonyl bond stretching mode with a shift in the comonomer ratio
      within the copolymer and by the ability to apply the Fineman-Ross
      copolymerization equation to describe copolymerization kinetics. Copolymers of
      methacrylic acid and ethylene dimethacrylate showed pH-dependent swelling
      behavior that was applied to the enteric release of fluorescein and ibuprofen.

PMID- 17429804
TI  - Ferrocene branched chitosan for the construction of a reagentless amperometric
      hydrogen peroxide biosensor.
AB  - Chitosan was chemically branched with ferrocene moieties and further used as a
      support for the immobilization of horseradish peroxidase on a glassy carbon
      electrode. The reagentless biosensor device showed a linear amperometric response
      toward hydrogen peroxide concentrations between 35 x 10(-6) M and 2.0 x 10(-3) M.
      The biosensor reached 95% of the steady-state current in about 20 s and its
      sensitivity was 28.4 x 10(-3) microA x M(-1). The enzyme electrode retained 94%
      of its initial activity after 2 weeks of storage at 4 degrees C in 50 x 10(-3) M
      sodium phosphate buffer at pH 7.0.

PMID- 17429805
TI  - Homogeneous tritylation of cellulose in 1-butyl-3-methylimidazolium chloride.
AB  - 1-Alkyl-3-methylimidazolium-based ionic liquids, having chloride as a counter
      ion, were studied for cellulose solubility; and the influence of different alkyl
      chain lengths was also investigated. The alkyl chain length was incrementally
      varied from ethyl to decyl to determine structure-dissolution properties; a
      distinct odd-even effect was observed for short chain lengths. In addition, the
      tritylation of cellulose was performed in 1-butyl-3-methylimidazolium chloride
      using pyridine as base. The influences of reaction time and the ratio of trityl
      chloride per cellulose monomer unit on the degree of substitution were
      investigated in detail by elemental analysis and 1H NMR spectroscopy. A DS of
      around 1 was obtained after 3 h reaction time using a six fold excess of trityl
      chloride.

PMID- 17429806
TI  - Synthesis and characterization of degradable p(HEMA) microgels: use of acid
      labile crosslinkers.
AB  - New divinyl-functionalized acetal-based crosslinkers were synthesized as building
      elements to form acid-labile microgel particles for controlled-release
      applications. The synthesized crosslinkers underwent hydrolysis at slightly
      acidic pHs in less than 1 h while they were stable at neutral pHs for longer
      times. HEMA was copolymerized with the crosslinkers via an inverse emulsion
      polymerization technique using a redox initiator system at room temperature to
      form crosslinked, colloidal p(HEMA) microgels. Microgels in diameters ranging
      from 150 to 475 nm with narrow distribution could be produced. The crosslinking
      density and the diameter of the microgels were found to be controlled by
      monomer/crosslinker feed ratio. The microgels demonstrated a pH-dependent
      cleavage behavior that mimicked the pH-dependent hydrolysis profile of the acid
      labile crosslinkers. Model biomacromolecules, i.e., Rhodamine B-labeled dextran
      and BSA were efficiently loaded into the microgels. The release of the
      biomolecules from p(HEMA) microgels was also found to be controllable by the pH
      of the environment similar to the particle degradation. The protein released from
      the microgels was observed to retain its structural stability.

PMID- 17429807
TI  - Investigation of a Cu(II)-poly(gamma-glutamic acid) complex in aqueous solution
      and its insulin-mimetic activity.
AB  - The complexation between cupric ions (Cu(II)) and poly(gamma-glutamic acid)
      (gamma-PGA) in aqueous solutions (pH 3-11) has been studied by UV-visible
      absorption and electron spin resonance (ESR) techniques. Formation of the Cu(II)
      gamma-PGA complex is confirmed by the observation of the blue shift of the
      absorption band in the visible region, anisotropic line shapes in the ESR
      spectrum at room temperature, and a computer simulation of the visible absorption
      spectrum of the complex. The structure of the Cu(II)-gamma-PGA complex, depending
      on the pH, has been determined. The in vitro insulin-mimetic activity of the
      Cu(II)-gamma-PGA complex is examined by determining both inhibition of free fatty
      acid release and glucose uptake in isolated rat adipocytes treated with
      epinephrine, in which the concentration of the Cu(II)-gamma-PGA complex for 50%
      inhibition of free fatty acid release is very similar to that of CuSO4. However,
      it is significantly lower than that of a previously reported insulin-mimetic
      bis(3-hydroxypicolinato)copper(II), [Cu(3hpic)2], complex.

PMID- 17429808
TI  - Efficient modification on PLLA by ozone treatment for biomedical applications.
AB  - RGDS (Arg-Gly-Asp-Ser) is immobilized on poly(L-lactic acid) (PLLA) with ozone
      oxidation and the addition of an intermediate reactant, acryl succinimide (ASI)
      to promote the grafting efficiency. A DPPH (2,2-di(4-tert-octylphenyl)-1
      picrylhydrazyl) assay has revealed that the peroxide concentration can be
      controlled by adjusting the ozone treatment time. The immobilization of ASI is
      verified by elemental analysis. The peptide concentrations are in the effective
      order, as shown by means of high performance liquid chromatography (HPLC), and
      the grafting efficiency is proven to be relatively high compared with the
      previous studies. The culture of rat osteosarcoma 17/2.8 (ROS), osteoblastic-like
      cells, demonstrates that the grafting of RGDS can enhance the attachment and
      osteogenesis of ROS cells on PLLA. With the addition of ASI, the cultured ROS
      cells express normal function in proliferation and mineralization. From in vivo
      experiments, ASI immobilized on the surface is shown to be biocompatible. These
      results lead to the conclusion that the ozone treatment with the intermediate
      reactant ASI is an efficient, biocompatible, and easily controllable procedure to
      modify PLLA. Furthermore, the immobilization of RGDS in significant amounts
      following the ozone oxidation could further promote the biocompatibility and the
      osteoinduction of PLLA.

PMID- 17429809
TI  - Hydration characterization of hydrophobically modified polymers by dielectric
      measurements in the millimeter range.
AB  - Bound water molecules, the fraction of water molecules that are present in the
      hydration shells of polymers, lose their rotational mobility in the time scale of
      10-50 ps, leading to additional ordering compared with unperturbed water. The
      amount of bound water per number of carbons in the nonpolar groups as measured by
      the method of waveguide dielectric resonance increased in the following order:
      hydrophobically modified chitosan < globular protein < hydrophobically modified
      polyacrylamide. The hydrophobic modification of acrylamide and chitosan polymers
      gave smaller variation in hydration than did both the coil-to-globule transition
      of poly(N-isopropylacrylamide) and the masking of nonpolar groups within the
      protein globule.

PMID- 17429810
TI  - Cell migration rate on poly(epsilon-caprolactone)/poly(ethylene glycol) diblock
      copolymers and correlation with the material sliding angle.
AB  - The nanostructure of a biomaterial surface has strong influence on cell behavior.
      The migration of cells on nanostructured surfaces, however, has not been
      investigated so far. In this study, we used PCL/PEG diblock copolymers as model
      surfaces to examine the effect of nanoislands on migration of different cells,
      including fibroblasts and endothelial cells. The water sliding angle of the
      substrates was measured. The cell migration rate was examined under a real-time
      optical microscope. It was found that a greater cell migration rate correlated
      with the smaller sliding angle of the substrate.

PMID- 17429811
TI  - Poly(epsilon-caprolactone)-poly(oxyethylene) multiblock copolymers bearing along
      the chain regularly spaced pendant amino groups.
AB  - Poly(epsilon-caprolactone) (PCL) macromers (M(n) = 1.7-3.8 kDa) which contain one
      Z-protected -NH2 group per chain were synthesized by ring-opening polymerization
      of epsilon-caprolactone in the presence of Sn(oct)2 using as initiator a diamine
      prepared by condensation of N-Boc-1,6-hexanediamine and N(alpha)-Boc-N(epsilon)-Z
      L-Lysine. The coupling of these macromers with -COCl end-capped poly(oxyethylene)
      (PEO), M(n) = 1.0 kDa, afforded amphiphilic multiblock poly(ether ester)s (PEEs)
      which have, along the chain, regularly spaced pendant protected amino groups.
      Deprotection, accomplished without chain degradation, yielded -NH2 groups
      available for further reactions. The molecular structure of macromers and PEEs
      was investigated by 1H NMR and SEC. DSC and WAXS analyses showed that macromers
      and copolymers were semicrystalline and their T(m) increased with increase in the
      molecular weight of PCL segments. The inherent viscosity values (0.25-0.30 dL x
      g(-1)), together with SEC analysis results, indicated moderate polymerization
      degrees.

PMID- 17429812
TI  - Biotechnological production of spider-silk proteins enables new applications.
AB  - The outstanding mechanical properties of spider silks have motivated many
      researchers to establish biotechnological production techniques which are
      necessary to provide sufficient amounts of silk proteins for industrial
      applications. Based on recent developments in genetic engineering, two strategies
      for the recombinant production of spider-silk proteins have been established
      which are discussed in detail. Further, protein-design strategies are described,
      enabling the combination of silk properties with additional biological, chemical,
      or technical features. We highlight the potential of engineered and recombinantly
      produced spider-silk proteins to provide the basis for a new generation of
      biomaterials.

PMID- 17429814
TI  - Regular dislocation networks in silicon as a tool for nanostructure devices used
      in optics, biology, and electronics.
AB  - Well-controlled fabrication of dislocation networks in Si using direct wafer
      bonding opens broad possibilities for nanotechnology applications. Concepts of
      dislocation-network-based light emitters, manipulators of biomolecules, gettering
      and insulating layers, and three-dimensional buried conductive channels are
      presented and discussed. A prototype of a Si-based light emitter working at a
      wavelength of about 1.5 microm with an efficiency potential estimated at 1% is
      demonstrated.

PMID- 17429815
TI  - Nonhydrolytic alcoholysis route to morphology-controlled ZnO nanocrystals.

PMID- 17429816
TI  - Photoinduced nanoscale cooperative motion in a well-defined triblock copolymer.

PMID- 17429819
TI  - ZnO: material, physics and applications.
AB  - ZnO is presently experiencing a research boom with more than 2000 ZnO-related
      publications in 2005. This phenomenon is triggered, for example, by hope to use
      ZnO as a material for blue/UV optoelectronics as an alternative to GaN, as a
      cheap, transparent, conducting oxide, as a material for electronic circuits that
      are transparent in the visible or for semiconductor spintronics. Currently,
      however, the main problem is to achieve high, reproducible and stable p-doping.
      Herein, we critically review aspects of the material growth, fundamental
      properties of ZnO and ZnO-based nanostructures and doping as well as present and
      future applications with emphasis on the electronic and optical properties
      including stimulated emission.

PMID- 17429817
TI  - Controlled growth and characterization of two-dimensional single-walled carbon
      nanotube networks for electrical applications.
AB  - We demonstrate the reproducible fabrication of single-walled carbon nanotube
      (SWNT) networks, via catalyzed chemical vapor deposition (cCVD). Fe nanoparticles
      are employed as the catalyst, with methane as the carbon-containing gas. cCVD
      growth under these conditions results in the formation of multiply
      interconnected, random, two-dimensional networks of SWNTs. Investigation of the
      effect of parameters such as methane flow rate and temperature on the growth
      process enables control over the density of the network, which controls the
      network conductivity. Low-density networks demonstrate p-type semiconductor
      behavior, whilst high-density networks exhibit semimetallic behavior. In both
      cases conductance is demonstrated over macroscopic length scales, up to
      millimeters, much longer than the individual SWNTs, despite the surface coverage
      being <1 %. The networks can be defined in regions of a surface by
      photolithography before or after growth. Controlled growth of SWNT networks thus
      enables the application of SWNTs as macroscale conductors with controllable,
      predictable, and reproducible characteristics.

PMID- 17429820
TI  - Enantioselective hydrogenation with self-assembling rhodium phosphane catalysts:
      influence of ligand structure and solvent.
AB  - Three sets of new and related chiral phospholane and phosphepine ligands have
      been prepared for Rh-catalyzed enantioselective hydrogenation. The size and
      substitution pattern of the cyclic monophosphanes were varied. More importantly,
      the ligands differ in the nature of the heterocyclic group linked to the
      trivalent phosphorus atom: 2-pyridone or 2-alkoxypyridine. In the corresponding
      Rh complexes, the pyridone units of two monodentate P ligands can assemble by
      hydrogen bonding and form chelates. In contrast, synthetic precursors bearing
      alkoxypyridine appendages are not able to aggregate via intramolecular hydrogen
      bonds. The nature of self-assembly is dependent on the nature of the P ligand and
      the solvent used for the hydrogenation (CH2Cl2 vs. MeOH). These features affect
      the rate of the reaction as well as the enantioselectivity, which varied in the
      range of 0-99 % ee Complexation studies and DFT calculations were performed to
      explain these differences.

PMID- 17429821
TI  - Chirality induction and protonation-induced molecular motions in helical
      molecular strands.
AB  - The long oligopyridinedicarboxamide strand 9, containing 15 heterocyclic rings
      has been synthesized and its helical structure determined by X-ray
      crystallography. It was shown that the shorter analogue 6 displays induced
      circular dichroism and amplification of induced chirality upon dissolution in an
      optically active solvent, diethyl-L-tartrate. A novel class of helical foldamers
      was prepared, strands 14-16, based on two oligopyridine carboxamide segments
      linked through a L-tartaric acid derived spacer. These tartro strands display
      internal chirality induction as well as chirality amplification. NMR spectroscopy
      (on 8 and 9) and circular dichroism (on 16) studies show that the oligopyridine
      carboxamide strands undergo reversible unfolding/folding upon protonation. The
      protonation-induced unfolding has been confirmed by X-ray crystallographic
      determination of the molecular structure of the extended protonated heptameric
      form 8(+). The molecular-scale mechano-chemical motions of the protonation
      induced structural switching consist of a change of the length of the molecule,
      from 6 angstroms (6, coiled form) to 29 angstroms (8(+), uncoiled form) for the
      heptamer and from 12.5 angstroms (9, coiled form, X-ray structure) to 57
      angstroms (9(+), uncoiled form, from modeling) for the pentadecamer. Similar
      unfolding/folding motional processes take place in the L-tartro strands 15 and 16
      upon protonation/deprotonation, with loss of helicity-induced circular dichroism
      on unfolding as shown for the protonated form 16(+).

PMID- 17429822
TI  - Synthesis of molecular motors incorporating para-phenylene-conjugated or
      bicyclo[2.2.2]octane-insulated electroactive groups.
AB  - The insulating role of the bicyclo[2.2.2]octane fragment has been theoretically
      evaluated by comparing the electronic coupling parameter (V(ab)) in 1,4
      bis(ferrocenyl)benzene (1) and 1,4-bis(ferrocenyl)bicyclo[2.2.2]octane (2). The
      geometries were optimized by DFT and an extended Huckel calculation was performed
      to evaluate V(ab) by the dimer splitting method. The calculations showed a 12
      fold decrease of the electronic coupling from 60 meV for 1 to 5 meV for 2. The
      second part describes the synthesis of two potential molecular motors with one
      incorporating the insulating bicyclo[2.2.2]octane fragment. These molecules are
      based on a ruthenium complex bearing a tripodal stator functionalized to be
      anchored onto surfaces. The ferrocenyl electroactive groups and the
      cyclopentadienyl (Cp) rotor are connected through a p-phenylene spacer (5) or
      through a spacer incorporating an insulating bicyclo[2.2.2]octane moiety (6).

PMID- 17429823
TI  - Identification of protein fold topology shared between different folds inhibited
      by natural products.
AB  - Natural products have withstood the test of time as therapeutics, but new lead
      generation strategies have focussed away from natural products. A new approach
      that uses natural-product recognition to drive an understanding of biological
      space might provide an impetus for renewed focus on natural-product starting
      points. Protein fold topology (PFT) has been shown to be an underlying factor for
      natural-product recognition. An investigation of natural product inhibitors of
      the Zincin-like fold has demonstrated their capacity also to inhibit targets of
      different fold types. Analysis of crystal structure complexes for natural
      products cocrystallised within different fold types has shown similarity at the
      PFT level. Two new PFT(T) (where subscript T denotes PFT shared between
      therapeutic targets) relationships have been established: the Zincin-like-
      metallohydrolase/oxidoreductase PFT(T) and the Zincin-like
      phosphorylase/hydrolase PFT(T). The PFT relationship between a natural product's
      biosynthetic enzyme and therapeutic target, and now between different fold
      targets of the same natural product, suggests that PFT is the simplest descriptor
      of biological space. This fundamental factor for recognition could facilitate a
      rational approach to drug development guided by natural products.

PMID- 17429824
TI  - Theoretical prediction and the first IR matrix observation of several L-cysteine
      molecule conformers.
AB  - For the first time the argon-matrix low-temperature IR spectra of cysteine are
      recorded. They reveal a quite complicated spectral pattern, which can also be
      reproduced in the N2 matrix. Assignment of the observed spectra is undertaken on
      the basis of comparison of the experimental and calculated B3LYP/aug-cc-pVDZ
      anharmonic IR spectra. The presence of at least three, and possibly even six or
      more, cysteine conformers with and without intramolecular hydrogen bonding is
      confirmed. On the basis of the calculated vibrational circular dichroism spectra,
      we predict this technique to be more distinctive for conformers than IR
      absorption is.

PMID- 17429825
TI  - A combined experimental and computational study on the ionization energies of the
      cyclic and linear C3H isomers.
AB  - For the first time, two hydrogen-deficient hydrocarbon radicals are generated in
      situ via laser ablation of graphite and seeding the ablated species in acetylene
      gas, which acts as a carrier and reactant simultaneously. By recording
      photoionization efficiency curves (PIE) and simulating the experimental spectrum
      with computed Franck-Condon (FC) factors, we can reproduce the general pattern of
      the PIE curve of m/z=37. We recover ionization energies of 9.15 eV and 9.76 eV
      for the linear and cyclic isomers, respectively. Our combined experimental and
      theoretical studies provide an unprecedented, versatile pathway to investigate
      the ionization energies of even more complex hydrocarbon radicals in situ, which
      are difficult to prepare by classical synthesis, in future experiments.

PMID- 17429827
TI  - Artificial polymeric flavonoids: synthesis and applications.
AB  - Flavonoids, one of the most numerous and best studied groups of plant
      polyphenols, are well known to exhibit various biological and pharmacological
      effects. Functional artificial polymeric flavonoids, flavonoid polymers and amine
      containing polymer-flavonoid conjugates have been developed. The acid-catalyzed
      polymerization of catechin and aldehydes proceeds regioselectively to produce
      catechin-aldehyde polycondensates. Peroxidases and laccases catalyze the
      oxidative coupling of flavonoids and oxidative conjugation with polyamines. The
      resulting polymers show much higher antioxidant activities than the flavonoid
      monomers. In addition, these polymeric flavonoids efficiently inhibit disease
      related enzymes, such as xanthine oxidase, collagenase, elastase, hyaluronidase
      and tyrosinase. Based on these results, the molecular design for amplification of
      the biological and pharmacological properties of flavonoids is proposed.

PMID- 17429828
TI  - Uniform biodegradable hydrogel microspheres fabricated by a surfactant-free
      electric-field-assisted method.
AB  - Uniform biodegradable hydrogel microspheres (HMS) with precisely controlled size
      have been fabricated using an electric-field-assisted precision particle
      fabrication technique. Particle agglomeration was prevented by charging the
      hydrogel drops and allowing Coulomb repulsion to separate them. As a result,
      surfactant-free and non-toxic particle fabrication was possible and the resulting
      microspheres were most suitable for biomedical and food-related applications. Due
      to the size uniformity, the present HMS may serve as a convenient yet most
      accurate vehicle for controlled delivery of therapeutic agents and other active
      ingredients.

PMID- 17429829
TI  - Fabrication and characterization of zein-based nanofibrous scaffolds by an
      electrospinning method.
AB  - Electrospun zein membranes were prepared using DMF as solvent. By changing the
      solution concentration, the electrospinning voltage and the distance between the
      spinneret and collector, nanofibrous meshes without bead defects could be
      obtained. In order to improve the mechanical strength of the hydrated zein
      meshes, core-shell-structured nanofibrous membranes with PCL as the core material
      and zein forming the shell were prepared by coaxial electrospinning. The core
      shell structure of the composite fibers was confirmed by SEM characterization of
      the fibers, either extracted with chloroform to remove the inner PCL, or
      elongated to expose their cross-section. The composition and average diameter of
      the composite fibers could be modulated by the feed rate of the inner PCL
      solution. It was found that the core-shell fibrous membranes have similar
      wettability to the electrospun zein mesh. The presence of PCL in the fibers could
      significantly improve the mechanical properties of the zein membrane.

PMID- 17429831
TI  - In vivo evaluation of a biodegradable EDC/NHS-cross-linked gelatin peripheral
      nerve guide conduit material.
AB  - Peripheral nerve regeneration has been evaluated using a biodegradable nerve
      conduit, which is made of a 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)/N
      hydroxysuccinimide (NHS) cross-linked gelatin. The EDC/NHS crosslinked gelatin
      (ENG) conduit is brownish in appearance, and is concentric and round with a
      smooth outer surface and inner lumen. After subcutaneous implantation on the
      dorsal side of a rat, the degraded ENG conduit only evoked a mild tissue
      response, with the formation of a thin tissue capsule surrounding the conduit.
      Biodegradability of the ENG conduit and its effectiveness as a guidance channel
      has been examined by its use to repair a 10 mm gap in the rat sciatic nerve. As a
      result, the tubes degraded throughout the implantation period, but still remained
      circular with a thin round lumen until they were completely integrated with the
      enclosed nerves. Successful regeneration through the gap occurred in all the
      conduits over the three experimental periods of 4, 8, and 12 weeks. Histological
      observation showed that numerous myelinated axons had crossed through the gap
      region even at the shortest implantation period of 4 weeks. Peak amplitude, area
      under the muscle action potential curve, and nerve conductive velocity all showed
      an increase as a function of the recovery period, which indicates that the nerve
      had undergone adequate regeneration. These results indicate the superiority of
      the ENG materials and suggest that the novel ENG conduits provide a promising
      tool for neuro-regeneration.

PMID- 17429832
TI  - ATPase-coupled release control from polyion complex capsules encapsulating muscle
      proteins.
AB  - In the present study, a muscle contractile protein complex, actomyosin, has been
      successfully encapsulated into gellan-chitosan polyion complex (PIC) capsules.
      The recovery of the myosin-ATPase activity is approximately 50% and the Mg2+
      ATPase activity is stimulated by the presence of F-actin, which implies the
      formation of the actomyosin complex inside the capsule. Furthermore,
      encapsulation could protect the myosin, F-actin, and actomyosin inside from
      hydrolysis by proteases. Two small proteins, myoglobin and cytochrome c, have
      been used in the release tests. The release of myoglobin is not affected by the
      ionic strength of the external solution, while the release of cytochrome c
      increases with increasing ionic strength. The maximal releases are found in the
      external pH solution close to the isoelectric points of each protein. The Mg2+
      ATP complex itself reduces the release percentages of the small proteins from the
      PIC capsule. The release amounts further decrease when coexisting with Mg2+-ATP
      and the encapsulated actomyosin, which indicates the release regulation by
      actomyosin. The present study suggests that the ATPase-coupled sliding motion of
      the myosin-F-actin filaments modifies the pore size of the polymer networks in
      the PIC capsule membranes.

PMID- 17429833
TI  - The impact of physical and psychosocial factors on work characteristics after
      cancer.
AB  - Most previously employed cancer survivors continue to work after treatment, but
      the impact of cancer symptoms or psychosocial concerns on their work has seldom
      been assessed. We conducted a community-based survey of cancer survivors from the
      Colorado Central Cancer Registry to assess the changes in their work and the
      demographic, clinical, and psychosocial characteristics associated with work
      changes over the 2 years following diagnosis. Of 100 survivors, 92 returned to
      work, but 57% of those reduced their work by more than 4 h/week, and 56% noted a
      change in some aspect of their occupational role. Physical symptoms, particularly
      lack of energy or nausea/vomiting, and psychological symptoms, particularly
      feeling bored or useless or feeling depressed, were significantly associated with
      a reduction in work hours or a change in occupational role. Since changes in work
      are common and are associated with both physical and psychosocial symptoms,
      strategies are needed to reduce symptom burden and barriers to work and to
      improve work capacity for working-age cancer survivors.

PMID- 17429834
TI  - Helping Her Heal: a pilot study of an educational counseling intervention for
      spouses of women with breast cancer.
AB  - Breast cancer is known to cause substantial anxiety, depressed mood, and
      diminished marital functioning in the diagnosed woman's spouse. Despite the scope
      and magnitude of these issues, few intervention studies have included spouses or
      addressed the causes of their lower functioning. The purpose of this pilot study
      was to evaluate the short-term impact of a 5-session, clinic-based, educational
      counseling intervention for spouses whose wife was recently diagnosed with early
      stage breast cancer. The goals of the intervention were to enhance spouses'
      skills and confidence to communicate and interpersonally support his wife about
      the breast cancer as well as improve spouses' self-care, depressed mood, anxiety,
      and marital adjustment. Pre-post-test results obtained from 20 spouses from valid
      and reliable standardized questionnaires showed significant improvements in
      spouses' depressed mood, anxiety, skills, self-confidence, and self-care.
      Confidential post-intervention interviews with spouses and wives included
      detailed examples of positive changes in the spouse's communication and support
      to his wife about the breast cancer, diminished tension in the spouse, and
      improved quality in the couple's relationship. Further evaluation of the Helping
      Her Heal Program is warranted within a clinical trial.

PMID- 17429835
TI  - Work disability associated with cancer survivorship and other chronic conditions.
AB  - The long-term effects of cancer and its treatment on employment and productivity
      are a major concern for the 40% of cancer survivors in the U.S. who are working
      age. This study's objectives were (1) to quantify the increase in work disability
      attributable to cancer in a cohort of adult survivors who were an average of 46
      months post-diagnosis and (2) to compare disability rates in cancer survivors to
      individuals with other chronic conditions. Data from the Penn State Cancer
      Survivor Study (PSCSS) and the Health and Retirement Study (HRS) were compared.
      The PSCSS sample included 647 survivors age 55-65, diagnosed at four medical
      centers in Pennsylvania and Maryland. There were 5988 similarly aged subjects
      without cancer in the HRS. Adjusted odds ratios for work disability were
      estimated for cancer survivorship, heart disease, stroke, diabetes, lung disease,
      and arthritis/rheumatism with multivariate logistic regression. Even for cancer
      free survivors, the adjusted disability rate was significantly higher in
      comparison to adults with no chronic conditions (female OR = 1.94; male OR =
      1.89). There were few significant differences between disability rates for cancer
      and other conditions. The elevated disability rate is another argument for
      viewing cancer survivorship as a chronic condition potentially requiring a broad
      range of psychosocial services.

PMID- 17429836
TI  - Imatinib compared with chemotherapy as front-line treatment of elderly patients
      with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL).
AB  - BACKGROUND: Elderly patients with Philadelphia chromosome-positive acute
      lymphoblastic leukemia (Ph+ALL) have a poor prognosis, with a low complete
      remission (CR) rate, high induction mortality, and short remission duration.
      Imatinib (IM) has a favorable toxicity profile but limited antileukemic activity
      in advanced Ph+ALL. Imatinib in combination with intensive chemotherapy has
      yielded promising results as front-line therapy, but its value as monotherapy in
      newly diagnosed Ph+ALL is not known. METHODS: Patients with de novo Ph+ALL were
      randomly assigned to induction therapy with either imatinib (Ind(IM)) or
      multiagent, age-adapted chemotherapy (Ind(chemo)). Imatinib was subsequently
      coadministered with consolidation chemotherapy. RESULTS: In all, 55 patients
      (median age, 68 years) were enrolled. The overall CR rate was 96.3% in patients
      randomly assigned to Ind(IM) and 50% in patients allocated to Ind(chemo) (P =
      .0001). Nine patients (34.6%) were refractory and 2 patients died during
      Ind(chemo); none failed imatinib induction. Severe adverse events were
      significantly more frequent during Ind(chemo) (90% vs 39%; P = .005). The
      estimated overall survival (OS) of all patients was 42% +/- 8% at 24 months, with
      no significant difference between the 2 cohorts. Median disease-free survival was
      significantly longer in the 43% of patients (21 of 49 evaluable) in whom BCR-ABL
      transcripts became undetectable (18.3 months vs 7.2 months; P = .002).
      CONCLUSIONS: In elderly patients with de novo Ph+ALL, imatinib induction results
      in a significantly higher CR rate and lower toxicity than induction chemotherapy.
      With subsequent combined imatinib and chemotherapy consolidation, this initial
      benefit does not translate into improved survival compared with chemotherapy
      induction.

PMID- 17429837
TI  - Loss of heterozygosity and human telomerase reverse transcriptase (hTERT)
      expression in bronchial mucosa of heavy smokers.
AB  - BACKGROUND: Lung carcinogenesis is a multistep process of accumulation of genetic
      changes, including loss of heterozygosity (LOH), and precedes phenotypic
      transformation of the bronchial mucosa. The activity of telomerase, correlating
      with the hTERT mRNA expression, is detectable in a majority of neoplasms. In this
      study, the frequency of LOH and hTERT expression in bronchial mucosa of heavy
      smokers in bronchoscopic biopsies was analyzed. METHODS: LOH was examined in 122
      bronchial specimens from 81 smokers (67 normal mucosa/bronchitis, 12 squamous
      metaplasia, 28 dysplasia, 15 bronchogenic carcinoma specimens) by polymerase
      chain reaction (PCR) and capillary electrophoresis by using 7 fluorescence
      labeled markers matching 5 chromosomal regions. hTERT expression was analyzed in
      87 specimens (45 normal mucosa/bronchitis, 12 squamous metaplasia, 18 dysplasia,
      12 bronchogenic carcinoma specimens) by real-time quantitative reverse
      transcription PCR. RESULTS: LOH was detected in at least 1 chromosomal region in
      51 of 122 (41.8%) specimens; the incidence in normal bronchial mucosa and
      preneoplastic lesions was similar (20%-40%); a substantial rise (87%) occurred in
      carcinomas. The median normalized hTERT(N) values were 6.67 in normal
      epithelium/chronic bronchitis, 18.38 in squamous metaplasia, 13.31 in epithelial
      dysplasia, and 75.46 in carcinomas. These results were significantly different
      (P=.0036). With an increasing number of LOH, the median value of hTERT(N)
      expression rose, but hTERT was expressed also in tissue samples without any LOH
      detection. CONCLUSIONS: Results indicated that hTERT expression, together with
      LOH, represent early events in lung carcinogenesis, as both were detected in
      precancerous lesions and in normal epithelium of heavy smokers.

PMID- 17429838
TI  - High prevalence of p53 exon 4 mutations in soft tissue sarcoma.
AB  - BACKGROUND: p53 is the most commonly mutated gene in cancer, including soft
      tissue sarcoma (STS). The authors characterized p53 alterations (protein
      accumulation and gene mutation) in STS to evaluate possible associations with
      patient outcomes. METHODS: Thirty-one STS specimens (multiple histologies) were
      analyzed by p53 immunohistochemistry (IHC) and direct DNA sequencing of p53 exons
      2-11 and then correlated with outcomes. RESULTS: Direct p53 sequencing detected
      mutations in 10 of 31 STSs; 7 of 10 were missense mutations, whereas 3 of 10 were
      either insertions or frameshift mutations, leading to nonfunctional truncated
      p53; 7 of these p53 mutations have not been previously described. Four p53 exon 4
      mutations were identified, a p53 region previously unknown to be mutation prone.
      Eighteen of the 31 specimens expressed p53 when the authors used the clinical IHC
      assay of their institution. Interassay concordance of 48% was observed; only 6 of
      10 sequencing-identified p53 mutated specimens exhibited nuclear p53 protein
      expression by IHC, whereas 12 of 18 specimens exhibiting p53 protein expression
      by IHC harbored sequencing-identified wild-type p53. Decreased survival was
      observed in STS patients bearing sequencing-identified mutated p53 versus wild
      type p53, as was a correlation between IHC-determined nuclear p53 protein
      expression and decreased survival. CONCLUSIONS: p53 protein stabilization and p53
      mutation frequently occur in STS, and both suggest worse outcomes for patients so
      affected. However, increased p53 protein expression does not necessarily indicate
      p53 gene mutation. The high incidence of exon 4 mutations found in STS suggests
      that p53 sequencing should not be limited to the core DNA binding domain.

PMID- 17429839
TI  - Infectious complications of monoclonal antibodies used in cancer therapy: a
      systematic review of the evidence from randomized controlled trials.
AB  - The introduction of monoclonal antibodies (MoAbs) into the treatment of cancer
      has led to improvements in patient survival. However, to the authors' knowledge,
      little attention has been paid to the infectious complications associated with
      their use. The authors performed a systematic review of the literature to
      identify randomized controlled trials (RCTs) that included in their outcomes a
      comparison of the infectious complications of a MoAb plus chemotherapy or
      radiotherapy versus the therapy regimen given without the addition of a MoAb.
      Twenty RCTs with relevant data regarding the use of MoAbs in patients with
      hematologic malignancies (10 RCTs) and solid tumors (10 RCTs) were retrieved. Six
      RCTs compared rituximab in conjunction with the combination of cyclophosphamide,
      doxorubicin, vincristine, and prednisone (CHOP) versus CHOP alone for the
      treatment of B-cell non-Hodgkin lymphoma (NHL). No significant increase in the
      incidence of infections was observed with the addition of rituximab to
      chemotherapy (based on data from 5 RCTs). However, in patients who were
      seropositive for the human immunodeficiency virus (HIV), a 12% increase in
      infection-related deaths and a rate of higher opportunistic infections was
      associated with the rituximab-containing regimen (data taken from 1 RCT). Five
      RCTs either compared trastuzumab plus chemotherapy versus chemotherapy alone or
      trastuzumab monotherapy versus observation in patients with breast cancer. The
      addition of trastuzumab to the various chemotherapy regimens was found to cause a
      slight increase in the frequency of high-grade infections while bevacizumab
      caused a negligible increase in Grade III/IV infections compared with the same
      regimens given of chemotherapy alone. Based on a single trial, a higher
      comparable increase in the rate of high-grade infections was noted with the use
      of cetuximab in addition to chemotherapy compared with chemotherapy alone. MoAbs
      added to chemotherapy appear to have infectious complications that are comparable
      to the chemotherapy-alone regimen when administered for the treatment of NHL,
      with the exception of HIV-seropositive patients. Trastuzumab, which is reported
      to have a clear benefit in the prognosis of breast cancer patients, was found to
      cause a small increase in Grade III/IV infectious complications; however, there
      was no apparent difference in the rate of infection-related death.

PMID- 17429840
TI  - WC1+ gammadelta T cell memory population is induced by killed bacterial vaccine.
AB  - Limited studies have addressed the ability of gammadelta T cells to become memory
      populations. We previously demonstrated that WC1.1(+) gammadelta T cells from
      ruminants vaccinated with killed Leptospira borgpetersenii proliferate and
      produce IFN-gamma in recall responses. Here we show that this response is
      dependent upon antigen-responsive CD4 T cells, at least across transwell
      membranes; this requirement cannot be replaced by IL-2. The response was also
      dependent upon in vivo priming, since gammadelta T cells from leptospira vaccine
      naive animals did not respond to antigen even when co-cultured across membranes
      from antigen-responsive PBMC. Gammadelta T cells were the major antigen
      responding T cell population for the first 4 wks following vaccination and
      replicated more rapidly than CD4 T cells. Primed WC1(+) gammadelta T cells
      circulated as CD62L(hi)/CD45RO(int)/CD44(lo), characteristics of T(CM) cells.
      When stimulated with antigen, they decreased CD62L, increased CD44 and CD25, and
      had no change in CD45RO expression. These changes paralleled those of the
      leptospira antigen-responsive CD4 T cells but differed from those of gammadelta T
      cells proliferating to mitogen stimulation. This system for in vivo gammadelta T
      cell priming is unique, since it relies on a killed antigen to induce memory and
      may be pertinent to designing vaccines that require type 1 pro-inflammatory
      cytokines.

PMID- 17429841
TI  - T lymphocyte rolling and recruitment into peripheral lymph nodes is regulated by
      a saturable density of L-selectin (CD62L).
AB  - L-selectin mediates tethering and rolling of lymphocytes in high endothelial
      venules (HEV) of lymph nodes (LN) and of leukocytes at inflammatory sites. We
      used transgenic mice expressing varying levels of wild-type or a non-cleavable
      mutant form of L-selectin on T cells to determine the relationship between L
      selectin density, tethering and rolling, and migration into LN. T cells
      expressing supraphysiological levels of either wild-type or non-cleavable L
      selectin showed rolling parameters similar to C57BL/6 T cells in hydrodynamic
      flow assays and during rolling in Peyer's patch HEV. In contrast, PMA- or antigen
      activated T cells and L-selectin(+/-) T cells expressing subphysiological levels
      of L-selectin showed reduced numbers of rolling cells with increased rolling
      velocity. Short-term homing studies showed that elevated expression of L-selectin
      above physiological levels had no effect on T cell migration to LN; however, low
      L-selectin expression resulted in reduced T cell homing to LN. Thus, T lymphocyte
      migration into LN is regulated by the density of cell surface L-selectin. In
      addition, there is a saturable density of L-selectin required for optimal homing
      to PLN in C57BL/6 mice, the L-selectin level on circulating naive T cells
      promotes optimal homing, and increased expression above saturating levels
      promotes no further increase in T cell recruitment.

PMID- 17429842
TI  - Transforming growth factor beta1 up-regulates interferon regulatory factor 8
      during dendritic cell development.
AB  - Langerhans cells (LC) represent the cutaneous contingent of dendritic cells (DC).
      Their development critically depends on transforming growth factor beta1 (TGF
      beta1) as demonstrated by analysis of TGF-beta1(-/-) mice, which lack LC. Here we
      used a two-step culture system and transcriptional profiling by DNA microarrays
      to search for TGF-beta1 target genes in DC. The study identified interferon
      regulatory factor 8 (IRF-8) as a novel target gene of TGF-beta1 signaling in DC.
      TGF-beta1 effectively induced Smad2/3 phosphorylation and IRF-8 RNA and protein
      expression. Blocking the TGF-beta1/Smad pathway by ectopic expression of
      inhibitory Smad7 and by SB431542 inhibitor abolished TGF-beta1 induced up
      regulation of IRF-8. Furthermore, TGF-beta1-dependent induction of IRF-8 occurred
      in the absence of protein biosynthesis, suggesting a direct action of TGF
      beta1/Smad signaling on IRF-8 gene activity. TGF-beta1 also induced expression of
      the chemokine receptor CCR7 and enhanced DC migration towards CCR7 ligand ELC. DC
      of IRF-8(-/-) mice show reduced CCR7 expression and migratory activity, thereby
      implicating the TGF-beta1/Smad/IRF-8 signaling pathway in CCR7 regulation. Thus,
      this study identified a novel TGF-beta1/Smad/IRF-8 signaling pathway with an
      impact on DC phenotype and function.

PMID- 17429843
TI  - The CD53 and CEACAM-1 genes are genetic targets for early B cell factor.
AB  - Early B cell factor (EBF)-1 is a transcription factor known to be of critical
      importance for early B lymphocyte development. EBF-1 has been shown to directly
      interact with and regulate expression of a set of genes involved in the
      functional formation of the pre-B cell receptor, but the dramatic phenotype
      observed in the EBF-1-deficient mice suggests that several additional genes are
      activated by this protein. In order to identify additional target genes for EBF
      1, we transduced a hematopoietic progenitor cell line, BaF/3, with an EBF-1
      encoding retrovirus and investigated the induced gene expression pattern by micro
      arrays. This analysis suggested that among others, the CD53 and the
      carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-1 genes both
      were induced by ectopic expression of EBF-1. Identification of the 5' end of the
      cDNA enabled the identification of promoter elements with functional binding
      sites for EBF-1 and ability to respond to EBF-1 expression in transient
      transfection assays. These data suggest that CD53 and CEACAM-1 are direct genetic
      targets for EBF-1, providing additional information concerning the activity of
      this crucial transcription factor in hematopoiesis.

PMID- 17429844
TI  - CD59a deficiency exacerbates influenza-induced lung inflammation through
      complement-dependent and -independent mechanisms.
AB  - Influenza-specific immune activity not only promotes virus clearance but also
      causes immunopathology, thereby underlining the importance of mounting a measured
      anti-viral immune response. Since complement bridges both the innate and adaptive
      immune systems and has been implicated in defence against influenza, the role of
      the complement regulator CD59a in modulating the response to influenza was
      explored. For this purpose, immune responses to influenza virus, strain E61-13
      H17, in mice deficient in the complement regulator protein CD59a (Cd59a(-/-)
      mice) were compared to those in wild-type mice. The severity of lung inflammation
      was significantly enhanced in the lungs of Cd59a(-/-) mice with increased numbers
      of infiltrating neutrophils and CD4(+) T cells. When complement was inhibited
      using soluble complement receptor 1, the frequency of lung-infiltrating
      neutrophils in influenza-infected Cd59a(-/-) mice was much reduced whilst numbers
      of CD4(+) T cells remained unchanged. These results demonstrate that CD59a,
      previously defined as a complement regulator, modulates both the innate and
      adaptive immune response to influenza virus by both complement-dependent and 
      independent mechanisms.

PMID- 17429846
TI  - Defective DNA methylation and CD70 overexpression in CD4+ T cells in MRL/lpr
      lupus-prone mice.
AB  - We have determined that abnormal DNA methylation in T cells coincides with the
      development of autoimmunity, using a mouse model that exhibits an age-dependent
      lupus-like disease (MRL/lpr mice). Splenic CD4(+) T cells were isolated from
      these mice at 5 and 16 wk of age (before and after autoimmunity is established)
      and the expression of DNA methyltransferase 1 (Dnmt1) and the methylation
      sensitive gene Tnfsf7 (CD70) was measured. Bisulfite DNA sequencing was used to
      monitor the methylation status of the Tnfsf7 gene. We found that Dnmt1 steady
      state mRNA levels were significantly lower in 16-wk-old MRL/lpr mice, which had
      established autoimmunity, compared to the 5-wk-old MRL/lpr mice. Furthermore, the
      expression of CD70 was higher in MRL/lpr mice at 16 wk. CD70 was overexpressed in
      MRL/lpr mice compared to age- and sex-matched MRL(+/+) controls. Bisulfite DNA
      sequencing of the Tnfsf7 gene in MRL/lpr mice revealed that at 16 wk, CG pairs
      were hypomethylated compared to 5-wk-old mice, and that Tnfsf7 from MRL/lpr mice
      was hypomethylated at 16 wk relative to age-matched MRL(+/+) controls. Our data
      indicate that decreased expression of Dnmt1 and the corresponding T cell DNA
      hypomethylation correlate with the development of age-dependent autoimmunity in
      MRL/lpr mice.

PMID- 17429845
TI  - Enhanced immunogenicity of CTL antigens through mutation of the CD8 binding MHC
      class I invariant region.
AB  - CD8(+) cytotoxic T lymphocytes (CTL) are key determinants of immunity to
      intracellular pathogens and neoplastic cells. Recognition of specific antigens in
      the form of peptide-MHC class I complexes (pMHCI) presented on the target cell
      surface is mediated by T cell receptor (TCR) engagement. The CD8 coreceptor binds
      to invariant domains of pMHCI and facilitates antigen recognition. Here, we
      investigate the biological effects of a Q115E substitution in the alpha2 domain
      of human leukocyte antigen (HLA)-A*0201 that enhances CD8 binding by
      approximately 50% without altering TCR/pMHCI interactions. Soluble and cell
      surface-expressed forms of Q115E HLA-A*0201 exhibit enhanced recognition by CTL
      without loss of specificity. These CD8-enhanced antigens induce greater CD3 zeta
      chain phosphorylation in cognate CTL leading to substantial increases in cytokine
      production, proliferation and priming of naive T cells. This effect provides a
      fundamental new mechanism with which to enhance cellular immunity to specific T
      cell antigens.

PMID- 17429847
TI  - Cooperation between CD4 and CD8 T cells for anti-tumor activity is enhanced by
      OX40 signals.
AB  - The relative contribution of OX40 (CD134) to priming of CD8 T cells in complex
      systems where CD4 and CD8 cells respond and cooperate together is not clear. We
      previously found that OX40 expressed on tumor-reactive CD8 T cells controls their
      initial persistence when adoptively transferred in vivo and is required for
      delayed tumor growth. We now show that exogenous stimulation of OX40 with agonist
      antibody augments its ability to suppress the growth of new as well as
      established tumors, correlating with marked expansion of adoptively transferred
      CD8 T cells. Concomitantly, anti-OX40 strongly enhanced the number of tumor
      antigen-reactive CD4 T cells. Moreover, the augmented accumulation of CD8 T cells
      was prevented in animals lacking MHC class II or depleted of CD4 cells and did
      not occur in OX40-deficient animals receiving wild-type CD8 cells, demonstrating
      that non-CD8 cells are the major target of OX40 signals. These results suggest
      that while OX40 signaling to a CD8 T cell can control its expansion, OX40
      expressed on non-CD8 cells strongly influences CD8 priming and in vivo activity.
      OX40 therefore represents an important signal for allowing effective cooperation
      between CD4 and CD8 cells and for promoting cell interplay and tumor rejection
      where CD8 activity is limiting.

PMID- 17429848
TI  - Identification and characterization of a novel antigen from the nematode
      Nippostrongylus brasiliensis recognized by specific IgE.
AB  - Identification and characterization of IgE-inducing antigens are important for
      elucidating the mechanisms involved in IgE-mediated immune responses in allergic
      diseases and parasite infections. While many allergens have been characterized,
      little is known about parasite antigens inducing specific IgE following
      infection. In order to identify antigens from the nematode Nippostrongylus
      brasiliensis, we generated an IgE-producing B cell hybridoma from N. brasiliensis
      infected C57BL/6 mice and constructed a cDNA phage display library from N.
      brasiliensis. We successfully cloned and expressed an N. brasiliensis antigen (Nb
      Ag1) that showed specific binding to anti-N. brasiliensis IgE. Nb-Ag1 localized
      to the pharynx of adult N. brasiliensis, suggesting that Nb-Ag1 is a potential
      pharyngeal gland antigen. Nb-Ag1-specific IgE could be detected in the serum of
      N. brasiliensis-infected mice, but only for a short time and only following a
      challenge infection. In contrast, local administration of Nb-Ag1 during primary,
      secondary and tertiary infections induced Nb-Ag1-specific IgE-mediated active
      cutaneous anaphylaxis. Therefore, amongst the high amounts of polyclonal total
      IgE, low levels of parasite-specific IgE responses are induced during primary
      helminth infections. Here, we show that even such low levels of parasite-specific
      IgE are sufficient to prime mast cells in vivo and mediate degranulation.

PMID- 17429849
TI  - Expression of CTLA-4 and FOXP3 in cis protects from lethal lymphoproliferative
      disease.
AB  - Both CTLA-4-deficient and FoxP3-deficient mice exhibit a short life span due to
      massive lymphoproliferation (LP) and a systemic autoimmune-like syndrome.
      Although it has been postulated that both diseases result from regulatory T cell
      (T(reg)) defects, there have been no direct complementation studies to elucidate
      their relationship in homeostatic lymphocyte proliferation during the neonatal
      period. In this study, reconstitution of sublethally irradiated RAG KO mice with
      either CTLA-4-deficient or FoxP3-deficient bone marrow (BM) resulted in LP
      disease similar to that observed in CTLA-4 KO or Scurfy mice, respectively.
      Although co-injection of BM from wild-type mice inhibited the activation of CTLA
      4-deficient or FoxP3-deficient T cells and ameliorated LP disease through
      extrinsic regulatory mechanisms by T(reg) cells, mice that had received the BM
      mixture of Scurfy and CTLA-4 KO BM eventually died of incomplete protection.
      These results suggest common attributes of both diseases, but expression of both
      CTLA-4 and FoxP3 on the same cell subset is essential to fully prevent LP
      disease.

PMID- 17429852
TI  - Noncovalently connected frameworks with nanoscale channels assembled from a
      tethered polyoxometalate-pyrene hybrid.

PMID- 17429851
TI  - Human skin permittivity determined by millimeter wave reflection measurements.
AB  - Millimeter wave reflection from the human skin was studied in the frequency range
      of 37-74 GHz in steps of 1 GHz. The forearm and palm data were used to model the
      skin with thin and thick stratum corneum (SC), respectively. To fit the
      reflection data, a homogeneous unilayer and three multilayer skin models were
      tested. Skin permittivity in the mm-wave frequency range resulted from the
      permittivity of cutaneous free water which was described by the Debye equation.
      The permittivity increment found from fitting to the experimental data was used
      for determination of the complex permittivity and water content of skin layers.
      Our approach, first tested in pure water and gelatin gels with different water
      contents, gave good agreement with literature data. The homogeneous skin model
      fitted the forearm data well. Permittivity of the forearm skin obtained with this
      model was close to the skin permittivity reported by others. To fit reflection
      from the palmar skin with a thick SC, a skin model containing at least two layers
      was required. Multilayer models provided better fitting to both the forearm and
      palmar skin reflection data. The fitting parameters obtained with different
      models were consistent with each other.

PMID- 17429853
TI  - Database of somatic mutations in EGFR with analyses revealing indel hotspots but
      no smoking-associated signature.
AB  - We created an Epidermal Growth Factor Receptor (EGFR) Mutation Database
      (http://www.cityofhope.org/cmdl/egfr_db) that curates a convenient compilation of
      somatic EGFR mutations in non-small-cell lung cancer (NSCLC) and associated
      epidemiological and methodological data, including response to the tyrosine
      kinase inhibitors Gefitinib and Erlotinib. Herein, we analyze 809 mutations
      collected from 26 publications. Four super hotspots account for 70% of reported
      mutations while two-thirds of 131 unique mutations have been reported only once
      and account for only 11% of reported mutations. Consistent with strong biological
      selection for gain of function, the reported mutations are virtually all missense
      substitutions or in-frame microdeletions, microinsertions, or microindels
      (colocalized insertion and deletion with a net gain or loss of 1-50 nucleotides).
      Microdeletions and microindels are common in a region of exon 19. Microindels,
      which account for 8% of mutations, have smaller inserted sequences (95% are 1 to
      5 bp) and are elevated 16-fold relative to mouse somatic microindels and to human
      germline microindels. Microdeletions/microindels are significantly more frequent
      in responders to Gefitinib or Erlotinib (P = 0.003). In addition, EGFR mutations
      in smokers do not carry signatures of mutagens in cigarette smoke. Otherwise, the
      mutation pattern does not differ significantly with respect to gender, age, or
      tumor histology. The EGFR Mutation Database is a central resource of EGFR
      sequence variant data for clinicians, geneticists, and other researchers. Authors
      are encouraged to submit new publications with EGFR sequence variants to be
      included in the database or to provide direct submissions via The WayStation
      submission and publication process (http://www.centralmutations.org).

PMID- 17429854
TI  - A tungsten-tin mixed hydroxide as an efficient heterogeneous catalyst for
      dehydration of aldoximes to nitriles.

PMID- 17429855
TI  - View from Damascus. Interview with Mohamad Amer Mahayni, MD by Jennifer Taylor.

PMID- 17429856
TI  - Changing times in Bulgaria. Interview with Tzvetana Marinova Katova MD, PhD, FESC
      by Barry Shurlock.

PMID- 17429857
TI  - Readers' response to "Time to reform physician relicensure".

PMID- 17429859
TI  - Readers' responses and author's reply to "The reality of 'traditional Chinese'
      medicines".

PMID- 17429858
TI  - Readers' response to "Time to reform physician relicensure".

PMID- 17429860
TI  - [Prescription references: preventing incompatibilities and instabilities].

PMID- 17429861
TI  - [Sentinel lymph node biopsy and incidence of recurrence].

PMID- 17429862
TI  - [What makes vaccines allergenic].

PMID- 17429863
TI  - Readers' responses and author's reply to "The reality of 'traditional Chinese'
      medicines".

PMID- 17429864
TI  - Readers' responses and author's reply to "The reality of 'traditional Chinese'
      medicines".

PMID- 17429865
TI  - Readers' responses and author's reply to "The reality of 'traditional Chinese'
      medicines".

PMID- 17429866
TI  - Readers' responses and author's reply to "The reality of 'traditional Chinese'
      medicines".

PMID- 17429867
TI  - Readers' responses and author's reply to "The reality of 'traditional Chinese'
      medicines".

PMID- 17429868
TI  - Readers' responses and author's reply to "The reality of 'traditional Chinese'
      medicines".

PMID- 17429870
TI  - Proceedings of the Symposium of Computations in Bioinformatics and Bioscience
      (SCBB06), Hangzhou, China, June 20-24, 2006.

PMID- 17429869
TI  - Readers' responses and author's reply to "The reality of 'traditional Chinese'
      medicines".

PMID- 17429871
TI  - Proceedings of APBioNet - Fifth International Conference on Bioinformatics
      (InCoB2006), New Dehli, India, 18-20 December 2006.

PMID- 17429872
TI  - Epidemiology of voice disorders in the elderly: preliminary findings.
AB  - OBJECTIVES: Epidemiologic studies of the prevalence and risk factors of voice
      disorders in the elderly, nontreatment seeking population are nonexistent. The
      purpose of this preliminary investigation was to 1) estimate the prevalence of
      voice disorders, 2) identify variables associated with increased risk of voice
      disorders, and 3) measure the socioemotional impact of voice disorders on the
      elderly who live independently. STUDY DESIGN: Prospective, cross-sectional
      survey. METHODS: One hundred seventeen seniors (39 males and 78 females; mean
      age, 76.1 yr; SD, 8.5 yr; range, 65-94 yr), residing in Utah and Kentucky, were
      interviewed using a questionnaire that addressed three areas related to voice
      disorders: prevalence, potential risk factors, and socioemotional
      consequences/effects. RESULTS: The lifetime prevalence of a voice disorder was
      47%, with 29.1% of participants reporting a current voice disorder. The majority
      of respondents (60%) reported chronic voice problems persisting for at least 4
      weeks. Seniors who had experienced esophageal reflux, severe neck/back injury,
      and chronic pain were at increased risk. Voice-related effort and discomfort,
      combined with increased anxiety and frustration and the need to repeat oneself,
      were specific areas that adversely affected quality of life. CONCLUSIONS: This
      preliminary epidemiologic study confirmed that voice disorders are common among
      the elderly, and further research is needed to identify additional risk factors
      contributing to voice disorder vulnerability.

PMID- 17429873
TI  - Metalloproteinase function in chronic rhinosinusitis with nasal polyposis.
AB  - OBJECTIVES: Chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma share
      characteristic inflammatory features and histopathologic findings of airway
      remodeling. Remodeling, which is controlled by matrix metalloproteinases (MMP),
      is a key event in the pathogenesis of asthma. The MMP functions have rarely been
      evaluated in CRSwNP. STUDY DESIGN: Prospective and in vivo. METHODS: MMP-7, MMP
      8, MMP-9, and tissue inhibitor of metalloproteinase (TIMP)-1 concentrations were
      analyzed by enzyme-linked immunosorbent assay and their molecular forms by
      Western immunoblotting and gelatin zymography in 24 patients operated on for
      CRSwNP and in nasal lavages from 19 healthy controls. MMP function, protective or
      destructive, was evaluated by comparing MMP/TIMP-1 levels with the disease
      activity, estimated by tissue eosinophilia and a need for re-operations. RESULTS:
      Significantly increased levels of MMP-8/TIMP-1 and MMP-9/TIMP-1 were found in
      patients without tissue eosinophilia relative to eosinophil-positive CRSwNP
      patients and controls, as well as in patients who did not require re-operation in
      comparison with re-operated patients. In eosinophil-positive and re-operated
      patients, these parameters were within the same range than in controls.
      CONCLUSIONS: Proteolytic spectrum is different in eosinophilic and
      noneosinophilic CRSwNP, suggesting a new mechanism for eosinophil accumulation in
      the disease pathogenesis. Enhanced MMP-8 and MMP-9 expression was associated with
      a better prognosis/clinical outcome, and thus these results may represent a
      synergic, protective role of MMP-8 and MMP-9 in host response in CRSwNP. Because
      synthetic MMP inhibitors, capable of equilibrating the unfavorable MMP/TIMP
      ratio, may be of potential therapeutic value in chronic respiratory tract
      diseases, the MMP functions in inflammatory conditions need to be carefully
      established.

PMID- 17429874
TI  - Concurrent cetuximab and bevacizumab therapy in a murine orthotopic model of
      anaplastic thyroid carcinoma.
AB  - OBJECTIVE: To evaluate the therapeutic efficacy of bevacizumab and cetuximab,
      alone and in combination, in an orthotopic model of anaplastic thyroid carcinoma
      (ATC) in athymic nude mice. STUDY DESIGN AND SETTING: This was a randomized,
      controlled in vivo study. MATERIALS AND METHODS: The ATC cell line, ARO, was used
      to establish orthotopic xenografts of ATC in athymic nude mice. Mice were
      randomized to therapy for 4 weeks in one of four treatment groups: placebo,
      cetuximab, bevacizumab, or the combination of cetuximab and bevacizumab. A second
      study compared the antitumor efficacy of the cetuximab-bevacizumab combination
      with doxorubicin. In both studies, tumor volumes on completion were measured and
      compared. Immunohistochemical analysis was performed with antiCD31 and
      antiproliferating cell nuclear antigen (PCNA) antibodies to assess the in vivo
      mechanisms of action of these agents. RESULTS: Cetuximab decreased the production
      of vascular endothelial growth factor by ATC cell lines in vitro. Mean tumor
      volumes for the control, bevacizumab, cetuximab, and combination groups at the
      end of the in vivo study were 291, 213, 94, and 42 mm(3), respectively. The
      differences in mean tumor volume for the control versus treatment groups were
      statistically significant. Immunohistochemical analysis showed decreased
      microvessel density and PCNA positivity in the treatment groups. In the
      doxorubicin comparison study, mean tumor volumes for control, doxorubicin, and
      combination antibody treatment groups were 175, 162, and 22 mm(3), respectively.
      CONCLUSIONS: Cetuximab and bevacizumab alone and in combination inhibit tumor
      growth and angiogenesis in an in vivo model of ATC. Also, this therapy was
      superior to doxorubicin therapy.

PMID- 17429875
TI  - Cochlear origin of early hearing loss in vestibular schwannoma.
AB  - OBJECTIVE: To test whether early hearing loss (HL) is cochlear in origin in
      patients with vestibular schwannoma (VS). STUDY DESIGN: Retrospective case review
      in an academic tertiary referral center. METHODS: A group of 19 VS patients with
      normal/symmetrical hearing and a group of 20 VS patients with mild HL (threshold
      at any tested frequency better than 45 dB HL) on the tumor ear side. Differences
      of the amplitudes of the distortion products of otoacoustic emissions (DPOAEs)
      between the tumor ear and the nontumor ear were studied at frequencies of 1, 1.4,
      2, 2.8, and 4 kHz. The Wilcoxon test was used to compare the ears for both groups
      and to test for possible differences in tumor size between groups. RESULTS: DPOAE
      amplitudes do not differ strongly between the ears in VS patients with
      normal/symmetrical hearing (two-sided P values: .050 at 1 kHz, .182 at 1.4 kHz,
      .378 at 2 kHz, .293 at 2.8 kHz, and .238 at 4 kHz) but are decreased compared
      with the nontumor ear at frequencies 1, 1.4, 2, and 2.8 kHz in VS patients with
      even mild HL (two-sided P values: .013 at 1 kHz, .007 at 1.4 kHz, .033 at 2 kHz,
      .010 at 2.8 kHz, and .156 at 4 kHz). Tumor size did not differ significantly
      between the two groups (P = .436). CONCLUSION: Amplitudes of DPOAEs begin to
      decrease even at the early stages of HL in VS patients, which suggests a cochlear
      origin of early HL in these patients. DPOAEs may be used in a clinical setting to
      monitor progression of cochlear damage at the early stages of hearing impairment
      in VS patients.

PMID- 17429876
TI  - Life expectancy. Know your gap.

PMID- 17429877
TI  - Cardiovascular disease. Focus on CVD.

PMID- 17429878
TI  - Early presentation. Detect cancer early.

PMID- 17429879
TI  - Health aspiration. Old is not ill.

PMID- 17429880
TI  - On-site clinics are for employers, not workers. Medicine at the workplace is not
      synonymous with occupational health.

PMID- 17429881
TI  - Former EN is grateful for support.

PMID- 17429883
TI  - Bridging the theory/practice gap.

PMID- 17429882
TI  - Raising money for herceptin.

PMID- 17429884
TI  - Palliative care nurses form group.

PMID- 17429885
TI  - Conference for surgical nurses.

PMID- 17429886
TI  - Data briefing. Variation in elective pathways.

PMID- 17429887
TI  - Access to emergency care.

PMID- 17429888
TI  - Access to emergency care.

PMID- 17429889
TI  - October Bulletin. Patient safety organizations "are the libretto for the next
      health care system".

PMID- 17429890
TI  - Office-based surgical facilities.

PMID- 17429892
TI  - Effective topical treatments for nongenital warts.

PMID- 17429891
TI  - Case report: Lemierre syndrome presenting with fever and pharyngitis.

PMID- 17429893
TI  - Another new theory explaining the cause of SIDS.

PMID- 17429894
TI  - Babies between a rock and a hard place--neonatologists vs parents at the edge of
      infant viability.

PMID- 17429895
TI  - Does Apgar score predict outcome in individual extremely preterm infants?

PMID- 17429896
TI  - Respiratory syncytial virus lower respiratory tract illness in infancy and
      subsequent morbidity.

PMID- 17429897
TI  - Genetic association studies in VLBW infants exemplifying susceptibility to sepsis
      -recent findings and implications for future research.
AB  - CONTEXT: In recent years, tremendous effort has been carried out to study the
      genetic basis of susceptibility to development, progression and severity of
      complex diseases and response to therapy. The ultimate goal of these
      investigations is to find new tools for prevention and treatment of these complex
      diseases, such as sepsis in very-low-birth-weight (VLBW) infants. VLBW cohorts
      have a restricted clinical risk profile for the development of sepsis including
      immaturity of immune functions and antenatal/perinatal risk factors but also a
      significant event rate of sepsis within a short period of observational time.
      Therefore, prospective VLBW cohorts are advantageous for the investigation of
      candidate genetic risk factors of sepsis compared to adult cohorts. Furthermore,
      environmental factors are much better documented and highly controlled for VLBW
      infants in a standardized NICU setting compared to adult cohorts which are
      influenced by a variety of environmental risk factors, e.g. habits and
      comorbidities. OBJECTIVE: The aim of this review is to discuss the value and
      limitations of genetic association studies in VLBW infant cohorts exemplifying
      recent findings for genetic susceptibility to neonatal sepsis. DATA SOURCE:
      Published Medline articles reporting on studies of associations between genetic
      polymorphisms, neonatal sepsis and septic shock in VLBW infants. CONCLUSIONS: Up
      to-date, the classical approach to investigate the genetic component of
      susceptibility to sepsis in VLBW infants by means of twin and concordance studies
      has not been implemented yet. Regarding the interpretation of data from current
      genetic association studies, one should be aware of significant differences in
      cohort size, study design and definition of cases, controls and clinical end
      points. Furthermore, the contribution of genetic variants to susceptibility to
      sepsis may be specifically influenced by the immaturity of the immune response in
      VLBW infants, the selectivity of responsiveness to certain pathogens and the
      genotopyic/phenotypic variability of pathogens. We provide implications for the
      conduct and evaluation of future association studies with particular reference to
      methodological quality standards.

PMID- 17429898
TI  - Apgar score predicts short-term outcome in infants born at 25 gestational weeks.
AB  - AIM: To identify early predictors of outcome in infants born at 25 gestational
      weeks. MATERIAL AND METHODS: Data from a regional perinatal database (time-period
      1995-2001, total n = 108 000 births) were used. Apgar scores were available in 92
      preterm infants, born at 25 + 0 to 25 + 6 gestational weeks, and analyzed in
      relation to short-term outcome (180-day survival with, or without, severe brain
      damage defined as intraventricular hemorrhage grade 3-4 or cystic periventricular
      leukomalacia). Based on multiple logistic regression analyses we constructed
      graphs of the estimated chance of survival. RESULTS: Apgar scores at 1, 5 and 10
      min correlated with survival without severe brain damage (p = 0.02, 0.006 and
      0.006, respectively). Survival without severe brain damage was higher in
      singleton than in multiple births (p = 0.03); there was no association with
      infant gender or mode of delivery. The strongest model for prediction of survival
      without severe brain damage was based on 5-min Apgar score and the Clinical Risk
      Index for Babies (CRIB), (p < 0.001). CONCLUSION: Apgar score predicts short-term
      outcome in extremely preterm infants at 25 gestational weeks. The precision for
      prediction of outcome increases when Apgar score is combined with CRIB.

PMID- 17429899
TI  - Role of TOPS (a simplified assessment of neonatal acute physiology) in predicting
      mortality in transported neonates.
AB  - AIM: To evaluate role of TOPS (a simplified assessment of neonatal acute
      physiology) in predicting mortality in transported neonates and to compare it
      with SNAP II. DESIGN: Prospective study. SETTING: Referral Neonatal Unit of a
      teaching hospital. SUBJECTS: 175 neonates > 1000 g admitted to referral nursery.
      METHODS: Temperature, oxygenation, capillary refill time (proxy for perfusion)
      and blood sugar (given the acronym of TOPS) were recorded at admission. SNAP II
      was also recorded for first 12 hours following admission. RESULTS: All the TOPS
      variables had significant correlation with fatality on univariate analysis.
      Fatality was 100% when all the four TOPS variables were deranged. The
      sensitivity, specificity, positive and negative predictive values of derangements
      of two or more TOPS parameters in predicting mortality were 81.6%, 77.39%, 65.3%
      and 89%, respectively All the variables of SNAP II significantly correlated with
      mortality. A cut-off score of 24 was derived from the ROC curve. The sensitivity,
      specificity, positive and negative predictive values of SNAP II score > 24 in
      predicting mortality were 78.3%, 86.1%, 74.6% and 88.4%, respectively. The area
      under ROC curve for derangements of 2 or more TOPS parameters was 0.89 while that
      for SNAP II was 0.88. Both models were well calibrated (p value for Hosmer
      Lemeshow goodness of fit for TOPS was 0.75 while that for SNAP II was 0.80). The
      total correct classification rate for TOPS was 81.7%, while that for SNAP II was
      83.4%. CONCLUSION: TOPS has an equally good prediction for mortality as SNAP II
      and can be used as a simple and useful method of assessment of risk of fatality
      that can be assessed immediately, at admission.

PMID- 17429900
TI  - Performance of neonatal ventilators in volume targeted ventilation mode.
AB  - AIM: To test the hypothesis that in volume targeted ventilation modes, ventilator
      performance would vary according to ventilator type. METHODS: Four neonatal
      ventilators: Draeger Babylog 8000 (Draeger Medical, Germany), SLE 5000 infant
      ventilator (SLE systems, UK), Stephanie paediatric ventilator (F. Stephan
      Biomedical, German) and V.I.P. Bird gold (Viasys Healthcare, USA) were assessed
      using a lung model. Delivered peak pressure, inflation time, mean airway pressure
      (MAP) and volume were measured. RESULTS: At the same preset ventilator settings,
      the Stephanie and V.I.P. Bird ventilators delivered significantly lower peak
      pressures and tended to deliver lower MAPs than the other two ventilators. At a
      volume targeted ventilation level of 5 mL, the SLE and the V.I.P. Bird delivered
      significantly shorter inflation times. The above differences related to
      differences in the airway pressure waveforms delivered by the four ventilators.
      The V.I.P. Bird had a less variable volume delivery, but this was always
      significantly lower than the preset volume guarantee level but higher than the
      volume displayed by the ventilator. CONCLUSION: In volume targeted ventilation
      modes, performance differs between neonatal ventilator types; these results may
      have implications for clinical practise.

PMID- 17429901
TI  - Is serum troponin T a useful marker of myocardial damage in newborn infants with
      perinatal asphyxia?
AB  - AIM: To assess the correlation of echocardiographic signs of myocardial damage to
      serum cardiac troponin T (cTnT) concentrations in newborn infants with perinatal
      asphyxia. METHODS: Electocardiograms (ECG) and echocardiograms (Echo) were
      obtained during the first 24 h of life from 29 asphyxiated and 30 control infants
      and correlated with cTnT concentrations. The echocardiographic parameters
      included systolic ventricular performance, preload, afterload, diastolic
      function, stroke volume (SV), left ventricular output (LVO), hyperechogenity of
      the papillary muscles and insufficiency of the atrioventricular valves. RESULTS:
      LVO and SV were lower but CTnT were significantly higher in asphyxiated than in
      control infants: 0.15 (010-0.23) vs. 0.05 (0.02-0.13), p < 0.001). Asphyxiated
      infants with signs of myocardial damage were associated with significantly higher
      cTnT than those without, 0.20 (0.11-0.28) and 0.11 (0.05-0.14 ug/L), p = 0.04.
      CONCLUSION: Cardiac troponin may prove to be valuable in evaluating myocardial
      damage in birth asphyxia. However, the degree of prematurity may complicate the
      assessment.

PMID- 17429902
TI  - Novel mutations in the gene encoding ATP binding cassette protein member A3
      (ABCA3) resulting in fatal neonatal lung disease.
AB  - AIM: To investigate whether intractable respiratory distress syndrome in three
      Norwegian term infants was due to mutations in the ABCA3 gene. METHODS: The genes
      encoding SP-B (SFTPB), SP-C (SFTPC), and ABCA3 (ABCA3) were sequenced from the
      parents of one infant and two unrelated infants with fatal neonatal lung disease.
      Lung tissue was examined by histology, immunohistochemistry and electron
      microscopy. RESULTS: Novel ABCA3 mutations were identified in each family. One
      patient had a phenotype differing from previous descriptions of this disease with
      an initial uneventful period. The diagnosis was established 19 years after death
      by analysing DNA material from the parents, with an ABCA3 mutation identified on
      one allele in each parent. The other two infants had more typical clinical
      courses with the onset of respiratory symptoms immediately after birth. ABCA3
      mutations were identified on both alleles from these two infants, and electron
      microscopy of alveolar type 2 cells demonstrated abnormal lamellar body formation
      characteristic of this disorder. CONCLUSION: ABCA3 mutations were the basis for
      lung disease in all three patients. Children with lung disease due to ABCA3
      deficiency may not have symptoms at birth. The finding of five novel mutations
      indicates allelic heterogeneity for ABCA3 mutations within the Norwegian
      population.

PMID- 17429903
TI  - Why do ALTE infants not die in SIDS?
AB  - AIM: To compare known risk factors for sudden infant death syndrome (SIDS)
      amongst infants with apparent life threatening events (ALTE) with their matched
      controls, and ALTE infants who subsequently died of SIDS with infants surviving
      an ALTE. METHODS: Questionnaires with replies were obtained from 58 ALTE infants
      and 56 sex and age matched ALTE control infants. 244 SIDS cases and 868 SIDS
      controls were used as comparison. RESULTS: The incidence of ALTE was found to be
      1.9% among SIDS controls, but 7.4% among infants who later on died of SIDS. The
      parents sought medical advice in 0.9% vs 3.7%. ALTE infants did not differ from
      their matched controls. In the ALTE group 13.3% of the survivors had the
      combination of prone sleeping and maternal smoking compared with 33.3% of those
      who became SIDS victims. CONCLUSIONS: Our results show some major differences
      between the ALTE infants and SIDS victims not supporting that these conditions
      belong to the same entity. However, we cannot exclude the possibility that there
      is a subpopulation of ALTE infants who did not die in SIDS due to that they were
      sleeping on the back and not exposed to nicotine.

PMID- 17429904
TI  - Cardiorespiratory events recorded on home monitors: the effect of prematurity on
      later serious events.
AB  - OBJECTIVE: To describe severe alarms on home-documented monitoring in infants
      born prematurely. METHODS: In infants born at a post-menstrual age (PMA) less
      than 35 weeks, a polysomnography was performed before discharge. A heart rate
      less than 50 beats per minute (bpm) for more than 3 seconds or an apnea lasting
      for more than 15 seconds with a heart rate less than 60 bpm were defined as
      abnormal. These babies were given cardiorespiratory home monitoring with memory.
      Serious alarms on the home monitor were defined as heart rate less than 50 bpm
      for more than 3 seconds. RESULTS: Of 1058 infants, 96 infants needed
      cardiorespiratory home monitoring. Sixty-one infants showed alarms at home. The
      mean post-conceptional age (PCA) when alarms stopped was 46 weeks. Seventeen
      patients had serious alarms above the PCA of 50 weeks. There was a significant
      negative correlation (r = -0.46 and p = 0.0002 by Spearman's rank correlation)
      between the PMA at birth and the PCA at which the last alarm was noted
      CONCLUSION: Prematurely born infants with an abnormal polysomnography at
      discharge are at high risk for developing acute events at home. A younger PMA at
      birth correlates with a higher risk of alarms at a later PCA.

PMID- 17429905
TI  - Is the mattress important in helping babies keep warm?--Paradoxical effects of a
      sleeping surface with negligible thermal resistance.
AB  - BACKGROUND: Heavy wrapping and head covering are risk factors for Sudden Infant
      Death Syndrome. A new mattress construction, PurFlo, has extremely low thermal
      resistance, and when used with an infant sleeping bag minimizes the risk of head
      covering. AIM: To investigate the thermal balance and metabolic rate of infants
      sleeping on a conventional mattress or a Purflo mattress in infant sleeping bags.
      METHODS: A longitudinal study of thermal balance of infants during day-time sleep
      on both mattress types in thermoneutral and cool conditions at ages 3 weeks (n =
      24), 3 months (n = 22) and 5 months (n = 18). RESULTS: In thermoneutral
      conditions axillary temperatures in quiet sleep were lower on the conventional
      mattress than on the PurFlo mattress (p < 0.05, Wilcoxon test). On lowering room
      temperature to 15-16 degrees C axillary temperatures fell, particularly in the
      older babies, and at each age were lower on the conventional mattress than the
      Purflo (differences 0.14-0.72 degrees C, p < 0.05, Wilcoxon test). CONCLUSION: In
      both thermoneutral and cool conditions, infant temperatures were higher on the
      PurFlo than the conventional mattress. The more deformable surface of the PurFlo
      mattress may lead to more effective insulation by the sleeping bag despite a lack
      of mattress insulation.

PMID- 17429906
TI  - A mitochondrial DNA polymorphism associated with cardiac arrhythmia investigated
      in sudden infant death syndrome.
AB  - AIM: Long QT syndrome (LQTS) has been shown to be the cause of death in some
      cases originally diagnosed as sudden infant death syndrome (SIDS). Such cardiac
      arrhythmias have also been noted in families with mitochondrial disease, and
      studies indicate that mitochondrial disease could be involved in SIDS. This makes
      the mtDNA polymorphism T3394C interesting, as a previous study has shown it to be
      associated with electrocardiographic (ECG) changes after exercise in a family
      with LQTS, where some members harboured a KCNH2 mutation. SUBJECTS: A total of
      245 SIDS cases and 176 control cases. METHODS: DNA was prepared from blood/tissue
      samples. Polymerase chain reaction (PCR) and restriction fragment length
      polymorphism (RFLP) were performed to search for the mtDNA polymorphism and KCNH2
      mutation. Differences were confirmed by sequencing. RESULTS: The T3394C
      polymorphism was found in 3 pure SIDS cases (1.5%), 2 borderline SIDS cases
      (4.4%), 1 case of explained death (1.6%) and 2 living control cases (1.8%) (p =
      0.62). The KCNH2 mutation was not found in cases or controls. CONCLUSION: The
      mtDNA polymorphism studied was found in a small number of SIDS cases and the
      frequency did not differ statistically from control subjects, making an
      association with increased SIDS risk unlikely.

PMID- 17429907
TI  - Mitochondrial tRNA genes and flanking regions in sudden infant death syndrome.
AB  - AIM: Mitochondrial DNA (mtDNA) mutations have been proposed as a genetic risk
      factor for sudden infant death syndrome (SIDS). The aim of this study was to
      further investigate this issue, by sequencing the mitochondrial tRNA genes with
      flanking regions in SIDS cases and controls. METHOD: The selected genes were
      investigated in 24 cases of SIDS and 10 controls, the method used were direct
      sequencing. In addition, the A10398G mutation in the ND3 gene was investigated in
      220 SIDS cases, 26 cases of infectious death and 93 controls, using allele
      specific PCR. RESULTS: Mutations, recorded as differences from the revised
      Cambridge sequence, were found in 32 different sites in the coding regions
      investigated. There was no difference in mutation frequency between SIDS cases
      and controls, and no single mutation was found associated with SIDS. CONCLUSION:
      The present study does not indicate an association between a specific
      mitochondrial tRNA gene mutation and SIDS, nor a higher mtDNA tRNA mutation
      frequency in SIDS cases than in controls.

PMID- 17429908
TI  - Visits by the family to the neonatal intensive care unit.
AB  - AIM: To investigate visiting frequency of family members, including mother,
      father, siblings and grandparents and associated factors during hospitalisation
      of preterm infants. METHODS: The study included all premature (< 37 weeks)
      infants born in Tampere University Hospital in 1997-1998 admitted to the neonatal
      intensive care unit (NICU) with a birth weight less than 2500 g (n = 210).
      Maternal and infant data and visits made by family members were compiled from the
      infants' hospital records. RESULTS: The length of the infants' hospitalisation
      varied from 2 to 133 days (median 26, quartiles 19, 45). Mothers visited the NICU
      on average 6.7 days/week; fathers 4.8 days/week. Mothers visited less frequently
      the lower the gestational age and the longer the distance between home and
      hospital. Fathers visited less frequently if distance from home to hospital was
      longer and if the infant had siblings. A total of 92% of siblings and 80% of
      grandparents visited the hospital. CONCLUSIONS: The results showed active
      visiting by the parents in the NICU. A lower gestational age was associated with
      lower visiting frequency for mothers. In contrast, more practical limitations
      such as geographical distance and other children to be taken care of had greater
      effect on the visiting frequency for fathers.

PMID- 17429909
TI  - Mode of delivery and threshold retinopathy of prematurity in pre-term ELBW
      neonates.
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial disease, but
      little is known about its relationship with perinatal risk factors. We tested the
      hypothesis that the mode of delivery may be associated with threshold ROP as
      defined by CRYO-ROP. METHODS: We conducted a prospective, cohort analysis of a
      database of all extremely low birth weight (ELBW) neonates (= birth weight < 1000
      g) admitted over a 8-year period from 1997 to 2004 to a large tertiary neonatal
      intensive care unit in a urban area of northern Italy and screened for ROP.
      Incidence of threshold ROP was calculated for the whole studied population. The
      definition of threshold ROP was as defined by the CRYO-ROP study. Univariate
      analysis was performed to look for significant associations between threshold ROP
      and several possible associated factors, and among them, the mode of delivery
      (vaginal delivery or caesarean section). When an association was indicated by p <
      0.05, multiple logistic regression was used to determine the factors
      significantly associated with ROP. RESULTS: Enrolled ELBW neonates were 174, and
      46 of them (26.4%) displayed threshold ROP. Threshold ROP occurred in 40.9% (27
      of 66) of the neonates vaginally delivered and in 17.5% (19 of 108) of those born
      via caesarean section (R.R. 3.35; 95% CI 1.230-4.855; p = 0.008 at univariate
      analysis, and = 0.04 at multivariate logistic regression after controlling for
      birth weight, gestational age, intraventricular haemorrhage grade 2 or more, days
      on supplemental oxygen, systemic fungal infection). Birth by vaginal delivery was
      not significantly associated with other major sequelae of prematurity
      (intraventricular haemorrhage, bronchopulmonary dysplasia, necrotizing
      enterocolitis). CONCLUSIONS: In our Institution birth by vaginal delivery is a
      significant and independent predictor of threshold ROP in ELBW infants. We
      suggest to consider closely ophthalmological surveillance for pre-term ELBW
      infants born this mode.

PMID- 17429910
TI  - Parental stress and toddler behaviour at age 18 months after pre-term birth.
AB  - AIM: To describe the parent's judgement of their own stress and the child's
      behaviour at 18 months after pre-term birth and if there are any correlations
      between these assessments, the morbidity in the neonatal period, the gestational
      age at birth and the occurrence of twin/triplet births. METHOD: Twenty-one
      mothers and 19 fathers of pre-term infants answered two questionnaires, The
      Swedish Parenthood Stress Questionnaire (SPSQ) and The Toddler Behaviour
      Questionnaire (TBQ). RESULTS: Mothers scored somewhat higher than fathers
      concerning parental stress. Parents with twins/triplets and of children born in
      gestational week 25-30 felt more stress, though the differences were not
      statistically significant. High-risk diagnoses did not correlate to any of the
      dimensions. The parents judged the behaviour of the children similar except that
      parents of children born in gestational week 25-30 scored significantly higher
      for intensity/activity (p = 0.002). The correlation between parental stress and
      judgement of their children's behaviour did not show any significant association
      except for the dimension regularity in TBQ (p = 0.016). CONCLUSIONS: The mothers'
      and fathers' assessments of their own stress and of the children's behaviour were
      similar. Parents of very pre-term children felt more stress and judged the
      children somewhat delayed in their social behaviours, probably due to their low
      gestational age.

PMID- 17429911
TI  - Oral glucose as an analgesic to reduce infant distress following immunization at
      the age of 3, 5 and 12 months.
AB  - AIM: To evaluate oral glucose as an analgesic to reduce infant distress after
      immunization during the first year of life and to investigate if these effects
      change during this period. METHODS: A prospective controlled trial of the
      effectiveness of glucose on crying response to immunizations at 3, 5 and 12
      months of age. A total of 110 infants were randomized to receive 2 mL of 30%
      glucose or water. The same solution was given at 3, 5 and 12 months. Crying was
      registered from onset of the injection up to 120 seconds. Infanrix Polio Hib was
      administered intra-muscular in the thigh. Observation nurse and parents were
      blind to the nature of the solution. RESULTS: Administration of glucose reduced
      the mean crying time by 22% at 3 months, 62% at 5 months and 52% at 12 months.
      The difference was significant at 5 and at 12 months. In the water group, there
      was a significant correlation between the children who cried at 3 months and who
      subsequently cried at 5 and 12 months. No correlations were found in the glucose
      group. CONCLUSION: Sweet solution can be used as a simple and safe method to
      reduce the distress following immunization in infants up to 12 months.

PMID- 17429912
TI  - Lack of recognition and complexity of foetal alcohol neuroimpairments.
AB  - AIMS: To obtain the recorded prevalence of foetal alcohol syndrome (FAS) and
      foetal alcohol spectrum disorders (FASD) in Norway, and evaluate the effect of a
      general information program to increase the recognition of FAS/FASD for health
      care and social workers. METHODS: A questionnaire regarding prevalence of
      FAS/FASD was sent to all Norwegian paediatric and child psychiatry departments.
      In the region Hordaland county, an information program was carried out to educate
      health-care and social workers on symptoms and signs of FAS/FASD, and referral
      was encouraged for suspected cases. Referred children received a neuropaediatric
      evaluation, and the effect of the information program on recorded FAS/FASD was
      recorded. RESULTS: Based on the national survey, a prevalence of 0.3 per 1000 was
      calculated. After the information program, the estimated prevalence in Hordaland
      County increased to 1.5 per 1000. In 5 years, 25 children were diagnosed with FAS
      and 22 with FASD. One-third of all children were mentally retarded. Microcephaly
      and neuroimpairments were more common among FAS children. Almost all children met
      the criteria of ADHD. CONCLUSION: The rate of FAS/FASD may be greatly
      underestimated because of lack of knowledge. An information program aimed at
      health-care and social workers is effective.

PMID- 17429913
TI  - The epidemiology and factors associated with nocturnal enuresis and its severity
      in primary school children in Taiwan.
AB  - PURPOSE: To investigate the prevalence of nocturnal enuresis among children in
      elementary school in Taiwan and to evaluate its associated factors and severity.
      MATERIALS AND METHODS: A randomly selected cross-sectional study was conducted
      from elementary schools in Changhua county, Taiwan in 2003. In all, 9228
      questionnaires were sent to 46 schools in 26 districts. RESULTS: A total of 92.1%
      (8496/9228) of questionnaires were completed. The overall prevalence of nocturnal
      enuresis was 6.8%. The ratio of male to female was about 1.5 (8.0% vs. 5.5%). The
      prevalence of enuresis according to age group declined from 12.5% at 6 years to
      2.0% at 12 years. The prevalence of enuresis in the urban area did not show
      significant difference from that of rural area (6.2% vs. 6.9%). Of the factors
      associated with enuresis, gender, age, urinary frequency or urgency, heredity,
      drinking habit before sleep and difficulty in waking showed significant
      difference after multiple logistic regression analysis. After multivariate
      analysis, difficulty in waking and time of wetting were the only factors
      significantly associated with the severity of enuresis. CONCLUSION: Our
      investigation showed the prevalence of enuresis is similar to those reports from
      the north of Taiwan and most of other western countries, but higher than that of
      China and Hong-Kong. Difficulty in waking and time of wetting were the only
      factors significantly associated with the severity of enuresis.

PMID- 17429914
TI  - Parent experiences of paediatric care (PEPC) questionnaire: reliability and
      validity following a national survey.
AB  - AIM: To describe the development and evaluation of a parent completed
      questionnaire to measure parent experiences of inpatient paediatric care, the
      parent experiences of paediatric care (PEPC). METHODS: Literature review, parent
      interviews, pre-testing and a national survey of 6144 parents of children who
      were inpatients at one of the 20 paediatric departments within Norway in 2005.
      RESULTS: Three thousand three hundred and eight (53.8%) parents responded to the
      questionnaire. Low levels of missing data suggest that the PEPC is acceptable.
      The questionnaire includes six scales as supported by the results of factor
      analysis: nursing services (seven items), doctor services (five items),
      organisation (four items), information--examinations and tests (two items),
      information--discharge (three items) and hospital facilities (four items).
      Cronbach's alpha and test-retest correlations ranged from 0.7 to 0.9. Comparisons
      of scale scores with several variables including overall satisfaction with care
      and pain control, supported validity. CONCLUSION: The PEPC questionnaire includes
      important aspects of hospital care from the perspective of the parent. It has
      good evidence for internal consistency, test-retest reliability and validity and
      is recommended in surveys of parent experiences of paediatric inpatient care.

PMID- 17429916
TI  - Determinants of breastfeeding initiation in Xinjiang, PR China, 2003-2004.
AB  - AIM: To identify the prevalence of breastfeeding initiation and the determinants
      of the breastfeeding initiation in Xinjiang, PR China, 2003-2004. METHODS: A
      cohort study of infant feeding practices was undertaken in Xinjiang Uygur
      Autonomous Region, PR China. A total 1219 mothers were randomly recruited in five
      hospitals or institutes located in urban and rural areas during 2003 and 2004.
      Multivariate logistic regression analysis was used to explore factors associated
      with breastfeeding initiation. RESULTS: Before discharge from hospital, 92.2% of
      the mothers were breastfeeding including 66.2% who were exclusively breastfed. A
      total of 88 mothers (7.8%) were not breastfeeding on discharge from hospital.
      Breastfeeding before discharge was positively associated giving breastmilk as the
      first feed (OR 4.05, CI 1.30-12.65) feeding on demand (OR 4.33, CI 1.69-11.08),
      when the mother felt she had been given enough information about breastfeeding,
      belonging to a minority ethnic group (OR 3.13, CI 1.21-5.05) and giving birth in
      spring or summer. CONCLUSIONS: This study has documented breastfeeding initiation
      rate and associated factors with it in Xinjiang, PR China.

PMID- 17429915
TI  - Effects of erythropoietin on erythrocyte deformability in non-transfused preterm
      infants.
AB  - AIM: Suppression of erythropoiesis due to low plasma erythropoietin levels is an
      important factor in the development of anaemia of prematurity. Premature infants
      may therefore be treated with recombinant human erythropoietin (rhEPO). This
      prospective, randomised and controlled study was designed to find out whether
      rhEPO treatment improves erythrocyte deformability in preterm infants. METHODS:
      Sixteen infants were treated with rhEPO (250 IU/kg three times weekly) a total of
      15 times beginning on day of life 5 whereas fifteen infants served as controls.
      Haemoglobin concentration, haematocrit, reticulocyte count, ferritin level and
      erythrocyte deformability were measured on days 5, 14, 28, 42 and 63. Erythrocyte
      elongation was determined as an indicator of erythrocyte deformability using a
      shear stress diffractometer (Rheodyn SSD) at shear forces of 0.3 to 60 Pa.
      RESULTS: Haemoglobin concentration was significantly higher on days 28 and 42 and
      reticulocyte percentage on day 28 in the rhEPO group compared to the controls.
      Serum ferritin was lower in the rhEPO group on day 28. Erythrocyte deformability
      was significantly increased on days 28 and 42 in the infants receiving rhEPO. We
      found a strong relationship between erythrocyte elongation and reticulocyte
      count. CONCLUSION: RhEPO markedly increases the erythropoiesis in preterm infants
      in the critical first weeks of life and the anaemia of prematurity is obviously
      reduced. The erythrocyte deformability improved under rhEPO treatment.
      Erythrocyte deformability was significantly related to the reticulocyte count
      indicating that the improvement of erythrocyte deformability was due to the
      formation of well-deformable young erythrocytes.

PMID- 17429917
TI  - The effects of swaddling on oxygen saturation and respiratory rate of healthy
      infants in Mongolia.
AB  - BACKGROUND: Infant swaddling is common practice in some developing countries
      where infant respiratory morbidity is also prevalent. Little is known about the
      effect of swaddling on respiratory variables in healthy infants. Such information
      could have important implications for respiratory diseases. AIMS: To compare
      respiratory rates (RR) and arterial oxygen saturations (SaO2) of healthy swaddled
      infants and non-swaddled infants during different conditions of sleep and
      arousal. SETTING: Community based, nested case control study in Ulaanbaatar,
      Mongolia. SUBJECTS AND METHODS: Habitually swaddled and non-swaddled infants aged
      9-10 weeks taking part in a randomised controlled trial of swaddling. Respiratory
      rate and SaO2 were measured during quiet wakefulness, feeding, quiet and active
      sleep. Habitually swaddled infants were studied in swaddled and non-swaddled
      conditions. Habitually non-swaddled infants were studied only in the non-swaddled
      state. RESULTS: SaO2 was higher during awake states compared with sleep states in
      all groups of infants. Habitually swaddled infants had lower mean SaO2 in the
      swaddled compared with non-swaddled condition (96.5% vs. 96.9%, p < 0.01) but
      these were not significantly different from the mean SaO2 of non-swaddled infants
      (96.9%, minimum p = 0.22). Habitually swaddled infants in the swaddled and non
      swaddled states had similar respiratory rates, but these were, in both cases,
      significantly lower than in habitually non-swaddled infants. CONCLUSION:
      Swaddling has little or no clinical effect on SaO2 or respiratory rates in
      healthy 9-10-week-old infants in Mongolia.

PMID- 17429918
TI  - Swedish pre-school children eat too much junk food and sucrose.
AB  - AIM: To analyze dietary intake in healthy 4-year-old children. METHODS: Families
      from three Paediatric Health Care Centres in different socio-economic areas in
      Goteborg completed 7-day food records and questionnaires about socio-economy.
      RESULTS: One hundred thirty two/153 completed the study, 49% of parents were
      university educated. Eighteen percent of children were overweight/obese. Energy
      intake was high; 67% had sucrose intake exceeding Nordic Nutrition
      Recommendations (NNR) but 36% had n-3 fatty acid intake < 0.5 energy percent.
      Significant negative correlations were found between sucrose and fat and between
      BMI and fat intake. Junk food supplied 24% of energy. Ninety-two percent had low
      vitamin D intake, 70% low iron and 21% low calcium intake. Gruel, which was
      consumed by 28%, had a positive impact on micronutrient intake. Child care and
      mother's origin seemed to influence dietary intake. CONCLUSION: In 4-year olds
      from well-educated urban families, 18% was overweight/obese. Total energy intake
      was above present NNR but lower than 20 years ago, when overweight was rare. Fat
      energy intake was negatively associated with BMI, and low n-3 fatty acid intake
      was associated with higher body weight. In several aspects dietary intake was not
      optimal in the children.

PMID- 17429919
TI  - Dieting in children: a population-based study in children aged between 9 and 12
      years.
AB  - AIM: Dieting can be a burden for the child and can have side effects. Insight
      into dieting is therefore important. A recent study showed that 13.7% (95% CI
      11.5-15.9%) of the children referred to a general paediatric outpatient clinic
      were or had been on a diet. However, it is unknown how many children in a random
      population are or have been on a diet. METHODS: Parents of children in the fifth
      grade of primary schools in the Dutch province of Friesland were asked to
      complete a structured questionnaire. RESULTS: From 2500 questionnaires 90% were
      returned. Two hundred and thirty-one children aged between 9 and 12 years had
      been on a diet (10.3%, 95% CI 9.0%-11.6%). A cow's milk free diet was used most
      frequently (50% of the dieting children). Other diets were: diets excluding
      additives (16%), peanuts (16%), sugar (15%) and lactose (11%). CONCLUSION: The
      use of diets by children in a general population is widespread: one in every ten
      children was or had been on a diet. Due to the known health risks associated with
      diets excluding one or more foods, such diets should only be advised by
      healthcare professionals.

PMID- 17429920
TI  - Nutritional state of Polish prepubertal children assessed by population-specific
      and international standards.
AB  - OBJECTIVE: To assess the frequency of obesity, overweight and underweight
      (thinness) in Polish 7-9-year-old children using a population specific definition
      as compared to the French, US and IOTF references based on body mass index (BMI).
      DESIGN: Height and weight were measured and BMI was calculated in a randomly
      selected representative sample of 7-9-year-old Polish children (N = 2916; 1445
      girls; 1471 boys) to define their nutritional status. Overweight (including
      obesity) was estimated according to four and underweight (thinness) according to
      three definitions Polish national references; French references; United States
      references and International Obesity Task Force references. RESULTS: According to
      Polish, French, U.S. and IOTF references overweight (including obesity) was found
      in 12.1, 14.3, 20.7 and 15.4% of children, respectively; 3.5, 9.4 and 3.6% of
      children were obese according to national, U.S. and IOTF references, respectively
      while underweight (thinness) was present in 6.9, 2.6 and 4.2% of children
      according to Polish, French and U.S. references, respectively. A trend of
      decreasing overweight and increasing underweight through age classes was
      observed. CONCLUSION: The rates of underweight (thinness), overweight and obesity
      in Polish 7-9-year-old children calculated according to the national, French,
      U.S. and IOTF references were significantly different. Therefore even if the IOTF
      reference is considered superior for international epidemiological studies,
      population specific standards should probably coexist for clinical practice.

PMID- 17429921
TI  - Family and school determinants of overweight in 13-year-old Portuguese
      adolescents.
AB  - AIMS: To identify familial and school determinants of overweight in 13-year-old
      adolescents. METHODS: All 27 public and 19 (79%) private schools allowed to
      contact age eligible students, 77.5% accepting to participate (1116 girls, 1045
      boys). Self-administered questionnaires were completed and physical examination
      performed, including weight and height measurements. Overweight (> 95th
      percentile) and at risk of overweight (85th-95th) were defined using CDC
      standards. Its determinants were identified using logistic regression models,
      entering parents' education and all variables significantly associated in crude
      analysis. RESULTS: Prevalence of overweight (10.2%) and at risk of overweight
      (16.5%) was not influenced by type of school, vending machines and number of
      school canteen meals. In girls, the prevalence of body mass index (BMI) > 85th
      percentile increased significantly with decreasing age at menarche (45.7% if
      menstruating before 11-year and 13.2% when pre-menarche), and increasing parental
      BMI or time spent on sedentary activities. In multivariate analysis, age at
      menarche and increasing parental BMI remained significant risks in girls. In
      boys, besides parental BMI, ever smoking, sleeping < 9 h and sedentary leisure
      activities were significant determinants. CONCLUSIONS: Food offered at school had
      no significant impact on adolescents overweight, which was mainly dependent on
      parental anthropometrics and leisure time activities.

PMID- 17429922
TI  - Reasons for inconsistent condom use by rural South African high school students.
AB  - AIM: To describe the condom use practices of high school students, compare the
      beliefs of students who used condoms with those who did not, investigate gender
      differences in condom use and identify factors that prevent condom use. METHOD:
      Cross sectional descriptive study of sexually active grade 10 students at 28
      rural high schools who completed a self-reporting structured questionnaire.
      RESULTS: Of n = 353 students, mean age 17.50 y (SD 1.40), n = 249 (70.5%) males
      and n = 104 (29.5%) females (p < 0.005), n = 136 (38.5%) had used a condom at
      last sex. Students who used condoms differed from non-condom users in their
      beliefs that use of condoms did not imply lack of trust (p = 0.03), supported
      girls' requesting that their partners use condoms (p = 0.002), perceived greater
      social support (p < 0.005), and had more self-efficacy (p < 0.005). In the model,
      condom use at last sex was significantly associated with males (p = 0.03), age at
      first sex (p = 0.02), knowing a person infected with HIV/AIDS (p = 0.03), and
      condom use self-efficacy (p = 0.001). CONCLUSION: The low rate of condom use
      amongst these students during the AIDS epidemic is influenced by students' condom
      use self-efficacy, emphasizing the need for skills' training. The increasing
      mortality due to HIV/AIDS may be a cue that encourages condom use.

PMID- 17429923
TI  - Perceived pubertal timing, pubertal status and the prevalence of alcohol drinking
      and cigarette smoking in early and late adolescence: a population based study of
      8950 Norwegian boys and girls.
AB  - AIM: To study whether perceived pubertal timing is related to the prevalence of
      alcohol drinking and cigarette smoking among adolescent boys and girls. METHODS:
      The Young-HUNT study (95-97), conducted in Nord-Trondelag County in Norway,
      comprises information from 8950 students, aged 13-19 years. Odds ratios (OR) with
      95% confidence intervals (CI) related to alcohol drinking and cigarette smoking
      were estimated by logistic regression analyses. RESULTS: Boys and girls who
      perceived themselves as early matured were more likely to report more risky
      drinking than those who perceived themselves as being on time, both in middle
      school and high school. A nearly identical pattern was found for smoking.
      However, boys in middle school, who perceived themselves as late, were more
      likely to smoke than those who were on time. CONCLUSION: In both genders,
      perceived early maturation was associated with increased risk behaviour
      involvement. Perceptions of being early in combination with high pubertal status
      yielded the highest prevalence of alcohol and tobacco use.

PMID- 17429924
TI  - Weight gain in childhood and body composition at 18 years of age in Brazilian
      males.
AB  - AIM: To assess the association between weight gain at different time periods
      during childhood and measures of adiposity in late adolescence. METHODS: A
      population-based birth cohort carried out in Pelotas, a 320 000-inhabitant city
      in a relatively developed area in Southern Brazil. All newborns in the city's
      hospitals were enrolled in 1982. Weight gain from 0-1, 1-2, 2-4 and 4-15 years
      were expressed as changes in weight-for-age Z-scores relative to the NCHS/WHO
      reference. In 2000, 79% (2250) of all males were located when enrolling at the
      national Army. Weight and height were assessed. Body composition indicators (fat
      mass/height(2), lean mass/height(2), fat mass/lean mass(2.3)) were estimated
      through bioimpedance. Analyses were adjusted for maternal and social factors, as
      well as for gestational age. RESULTS: In the adjusted analyses, birthweight and
      weight gain in the first year of life were positively associated with attained
      height at age 18 years. Except for the fat mass/lean mass(2.3) ratio, all weight
      related outcomes were positively associated with weight gain in different periods
      of life. Children who gained weight rapidly in more than one time period became
      fatter at age 18 years, independently of when fast growth took place.
      CONCLUSIONS: Height was primarily determined by fetal and infant growth. Weight
      related indices, including the fat/lean mass ratio, were more strongly influenced
      by later growth. No clear critical windows of growth during which absolute tissue
      masses are programmed could be identified.

PMID- 17429925
TI  - Mental health problems, negative life events, perceived pressure and the
      frequency of acute infections among adolescents. Results from a cross-sectional,
      multicultural, population-based study.
AB  - AIM: To study the association between mental health problems, negative life
      events, perceived pressure at school and the frequency of acute infectious
      illnesses in an adolescent population, and to explore whether the association
      differs by sex and immigration status. METHODS: A cross-sectional study involving
      all tenth grade pupils in Oslo in 2000 and 2001. Of 8316 eligible pupils, 7346
      participated in the study, giving a participation rate of 88%. Twenty-four
      percent of participants were first- or second-generation immigrants. RESULTS:
      Mental health problems and negative life events were associated with the number
      of acute infections in a population-based setting, even after adjustment for
      possible confounding factors. For girls with an immigrant background,
      internalised mental health problems and own serious illness or injury had the
      strongest association with acute infections. For adolescents with a non-immigrant
      background, experiencing sexual violence had the strongest association, and for
      native-born boys the strongest association with acute infections was externalised
      mental health problems. Smoking was the cofactor with the strongest association
      to acute infections. CONCLUSION: There is a relationship between acute infection,
      mental health problems and negative life events among adolescents in a
      multicultural population-based setting.

PMID- 17429926
TI  - Phenotype of acute respiratory syncytial virus induced lower respiratory tract
      illness in infancy and subsequent morbidity.
AB  - The objective of this study was to investigate the association hypothesis that
      outcome following respiratory syncytial virus (RSV) induced bronchiolitis (RSVB)
      and RSV induced wheeze (RSVW) are different. At 3 years respiratory symptoms were
      more common in those with RSV infection than the control group but there was no
      increase in allergic sensitisation (11% vs 10%). Those with RSVW were more likely
      to have evidence of allergic sensitisation when compared with RSVB subjects (22%
      vs 7%), and have increased symptoms and increased use of inhaled steroids.
      CONCLUSION: The data argue that RSV infection during infancy does not induce
      allergic asthma and that host factors rather than the virus determine long-term
      outcomes.

PMID- 17429927
TI  - Noninvasive treatment of bronchomalacia, successful ventilation of a severely ill
      infant.
AB  - Noninvasive treatment of bronchomalacia. Successful ventilation of a severely ill
      infant. AIM: To describe an effective treatment of a boy with bronchomalacia by
      noninvasive mechanical ventilation support. METHODS: We describe a case of a
      severely ill patient with bronchomalacia from the time he was born and until the
      age of five. Bi-level positive airway pressure given through a specially adapted
      full face mask was used to treat his respiratory condition. RESULT: Our patient
      responded well to the noninvasive treatment of bronchomalacia. CONCLUSION: We
      found that noninvasive mechanical ventilation support is a low risk and highly
      effective treatment of infants and children with respiratory distress caused by
      bronchomalacia.

PMID- 17429928
TI  - Topical tacrolimus is effective against eczema in Wiskott-Aldrich syndrome (WAS).
AB  - The Wiskott-Aldrich syndrome is a rare X-linked immunodeficiency characterized by
      microplatelet thrombocytopenia and eczema. Eczema may be severe and facilitate
      entry of microorganism into the host. CONCLUSION: We report for the first time
      that eczema in infants with WAS can be effectively treated with topical
      ttacrolimus.

PMID- 17429929
TI  - Hepatitis B e antigen positive mother hepatitis B e antigen long persistence in
      her non-infected baby.
AB  - We report the case of a baby born to a hepatitis B virus (HBV) carrier mother.
      This infant had a hepatitis B e antigen (HBeAg) in the serum until 6 months of
      age. Serial sera samples were analysed for HBV markers. No breakthrough of HBV
      infection was detected. The origin of this HBV marker has been questioned.
      CONCLUSION: HBeAg can persist at a non-infected baby born to an HBeAg-positive
      mother up to the age of 6 months.

PMID- 17429930
TI  - Selman A. Waksman (1888-1973) Nobel Prize in 1952 for the discovery of
      streptomycin, the first antibiotic effective against tuberculosis.

PMID- 17429931
TI  - Discrepancy of milk ghrelin level.

PMID- 17429932
TI  - Epidemiological study of constipation and other gastrointestinal symptoms in 8000
      children (Acta Paediatr 2006; 95: 573-580).

PMID- 17429933
TI  - The importance of considering children's- and adults'-cognitive functions when
      discussing living conditions and psychosomatic complaints.

PMID- 17429934
TI  - Moxibustion by midwives.

PMID- 17429935
TI  - Reduction of the role.

PMID- 17429937
TI  - Minn. systems settle billing suit. Credit vouchers offered to patients rather
      than cash.

PMID- 17429938
TI  - "Click labeling" with 2-[18f]fluoroethylazide for positron emission tomography.
AB  - As an effort in the development of more flexible (18)F-labeling chemistry, we
      report herein on the use of the Cu(I)-catalyzed Huisgen cycloaddition, also known
      as the "click reaction", to form (18)F-labeled 1,2,3-triazoles. Nucleophilic
      fluorination of 2-azidoethyl-4-toluenesulfonate followed by distillation provided
      2-[(18)F]fluoroethylazide in 55% radiochemical yield (decay-corrected). 2
      [(18)F]fluoroethylazide was reacted with a small library of terminal alkynes in
      the presence of excess Cu(2+)/ascorbate or copper powder. The most reactive
      alkyne, N-benzylpropynamide provided nearly quantitative incorporation of 2
      [(18)F]fluoroethylazide after 15 min at ambient temperature, whereas the majority
      of the alkyne substrates provided excellent yields of the corresponding (18)F
      labeled 1,2,3-triazoles following heating to 80 degrees C. Using the method
      described, a model peptide was obtained in 92.3 +/- 0.3% (n = 3) radiochemical
      yield (decay-corrected) after purification by semipreparative HPLC.

PMID- 17429939
TI  - Binding of streptavidin with biotinylated thermosensitive nanospheres based on
      poly(N,N-diethylacrylamide-co-2-hydroxyethyl methacrylate).
AB  - Thermosensitive polymer nanospheres based on N,N-diethylacrylamide and 2
      hydroxyethyl methacrylate (HEMA) have been prepared, characterized, and
      conjugated with biotin. The thermosensitivity of poly(N,N-diethylacrylamide) was
      enhanced by the incorporation of HEMA up to about 40 mol %. Atomic force
      microscopic images show that these particles can be closely packed even without
      the surface charges as in the latex particles. Biotinylation reduces the
      thermosensitivity of the copolymer nanospheres. The biotinylated hydrogel
      nanospheres showed a reduction in size upon binding with streptavidin, indicating
      the formation of a less hydrophilic conjugate. No aggregation of the biotinylated
      particles due to the cross-linking effect of streptavidin was observed. This size
      change could be reversed by the addition of free biotin to the system. The
      interaction is specific, and no such changes were observed when streptavidin was
      replaced by bovine serum albumin.

PMID- 17429940
TI  - Synthesis, characterization, and in vitro activity of dendrimer-streptokinase
      conjugates.
AB  - Dendrimer conjugation with low molecular weight drugs has been of increasing
      interest recently for improving pharmacokinetics, targeting drugs to specific
      sites, and facilitating cellular uptake. Opportunities for increasing the
      performance of relatively large therapeutic proteins such as streptokinase (SK)
      using dendrimers are being explored in this study. Using the active ester method,
      a series of streptokinase-poly(amido amine) (PAMAM) G3.5 conjugates were
      synthesized with varying amounts of dendrimer-to-protein molar ratios.
      Characterization of these conjugates by GPC, IEC, and native-PAGE suggested that
      the conjugation reaction was successful, resulting in relatively pure SK
      dendrimer conjugates. The conjugate made with an equimolar ratio of dendrimer to
      streptokinase (1:1) exhibited the highest enzymatic activity retention (
      approximately 80% retained) that has been reported so far for conjugated
      streptokinase with macromolecules such as PEG or dextran. SK conjugates with
      higher streptokinase-to-dendrimer molar ratios (1:10 and 1:20) exhibited lower
      initial enzymatic activities. However, these conjugates showed sustained
      thrombolytic activity in plasma, perhaps due to the release of SK from the
      conjugate. All of the SK conjugates displayed significantly improved stability in
      phosphate buffer solution, compared to free SK. The high coupling reaction
      efficiencies and the resulting high enzymatic activity retention achieved in this
      study could enable a desirable way for modifying many bioactive macromolecules
      with dendrimers.

PMID- 17429942
TI  - RGD-dependent mechanotransduction of suspension cultured Taxus cell in response
      to shear stress.
AB  - Plant cells cultured in bioreactors are strongly influenced by mechanical forces.
      However, the molecular mechanism of plant cell mechanoreception has maintained
      unclear. In animal cells, the Arg-Gly-Asp (RGD) motif can be found in proteins of
      the extracellular matrix. Integrins link the intracellular cytoskeleton of cells
      with the extracellular matrix by recognizing this RGD motif. Integrin has been
      demonstrated to function as an apparatus not only for adhesion but also for
      mechanotransduction. In plant cells, the molecules that mediate the structural
      continuity between wall and membrane are unknown. Here, we found that synthetic
      RGD peptide could dramatically reduce the level of phosphorylation of MAPK-like
      cascades that are activated by shear stress and reduce the alkalinization
      response, production of reactive oxygen species (ROS) and accumulation of
      phenolics by Taxus cuspidata cells during shear stress. These results implicate
      that a RGD recognition system may exist in Taxus cells and play an important role
      in signal transduction of shear stress. Although the Arabidopsis genome database
      shows that the plant seems to lack a homologue of animal integrin, plant cells
      may use other RGD-binding proteins to recognize the RGD motif. The correlative
      mechanism is discussed.

PMID- 17429941
TI  - In vitro biocompatibility of schwann cells on surfaces of biocompatible polymeric
      electrospun fibrous and solution-cast film scaffolds.
AB  - The in vitro responses of Schwann cells (RT4-D6P2T, a schwannoma cell line
      derived from a chemically induced rat peripheral neurotumor) on various types of
      electrospun fibrous scaffolds of some commercially available biocompatible and
      biodegradable polymers, i.e., poly(3-hydroxybutyrate) (PHB), poly(3
      hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), polycaprolactone (PCL), poly(l
      lactic acid) (PLLA), and chitosan (CS), were reported in comparison with those of
      the cells on corresponding solution-cast film scaffolds as well as on a tissue
      culture polystyrene plate (TCPS), used as the positive control. At 24 h after
      cell seeding, the viability of the attached cells on the various substrates could
      be ranked as follows: PCL film > TCPS > PCL fibrous > PLLA fibrous > PHBV film >
      CS fibrous approximately CS film approximately PLLA film > PHB film > PHBV
      fibrous > PHB fibrous. At day 3 of cell culture, the viability of the
      proliferated cells on the various substrates could be ranked as follows: TCPS >
      PHBV film > PLLA film > PCL film > PLLA fibrous > PHB film approximately PCL
      fibrous > CS fibrous > CS film > PHB fibrous > PHBV fibrous. At approximately 8 h
      after cell seeding, the cells on the flat surfaces of all of the film scaffolds
      and that of the PCL nanofibrous scaffold appeared in their characteristic spindle
      shape, while those on the surfaces of the PHB, PHBV, and PLLA macrofibrous
      scaffolds also appeared in their characteristic spindle shape, but with the cells
      being able to penetrate to the inner side of the scaffolds.

PMID- 17429943
TI  - Axial ion focusing in a miniature linear ion trap.
AB  - A novel miniature linear ion trap with a total length of 19 mm and a quadrupole
      rod length of 15 mm has been fabricated to enable ion focusing in the axial plane
      (between the end caps). Each end cap includes an inwardly projecting tubular
      section, which prevents dc fringe fields from penetrating to the center of the
      miniature linear ion trap and aids in ion extraction. Axial focusing of ion
      packets to dimensions of less than 1 mm through collisional cooling is predicted
      and demonstrated in the miniature linear ion trap. Due to this demonstrated
      collisional cooling, narrow kinetic energy distributions are also illustrated on
      batch ion extraction as might be useful for ion transfer to enable subsequent
      mass analysis.

PMID- 17429944
TI  - Characterization and optimization of gold nanoparticle-based silver-enhanced
      immunoassays.
AB  - Silver-enhanced nanoparticle-labeled immunoassays provide a simple, low-cost, and
      effective way of detecting antigens in dilute solutions. The physical mechanisms
      behind their operation, however, have not been fully investigated. We present a
      semiquantitative approach for optimizing sandwich nanoparticle immunoassays using
      an adsorption-controlled kinetic model. Primary antibodies were immobilized on a
      solid substrate to bind the target antigens in solution. An optical signal was
      measured by secondary labeling of antigens with gold nanoparticles and their
      enhancement by silver nucleation. The opacity of the silver-enhanced spots was
      quantified by densitometry. The selectivity of the sandwich immunoassays was
      adequately high, and antigen concentrations as low as 0.1 microg cm(-3) (4 ng
      total) were detected reproducibly. The role of mass transfer was investigated,
      and a model was developed to optimize the performance of immunoassays by
      correlating the opacities of silver spots to the concentration and incubation
      times of antigens and gold nanoparticles. The results could allow the development
      of more rapid and reliable nanoparticle immunoassays.

PMID- 17429945
TI  - Characterization of two types of silanol groups on fused-silica surfaces using
      evanescent-wave cavity ring-down spectroscopy.
AB  - Evanescent-wave cavity ring-down spectroscopy has been applied to a planar fused
      silica surface covered with crystal violet (CV+) cations to characterize the
      silanol groups indirectly. A radiation-polarization dependence of the adsorption
      isotherm of CV+ at the CH3CN/silica interface is measured and fit to a two-site
      Langmuir equation to determine the relative populations of two different types of
      isolated silanol groups. CV+ binding at type I sites yields a free energy of
      adsorption of -29.9 +/- 0.2 kJ/mol and a saturation surface density of (7.4 +/-
      0.5) x 10(12) cm(-2), whereas the values of -17.9 +/- 0.4 kJ/mol and (3.1 +/-
      0.4) x 10(13) cm(-2) are obtained for the type II sites. The CV+ cations, each
      with a planar area of approximately 120 A2, seem to be aligned randomly while
      lying over the SiO- type I sites, thereby suggesting that this type of site may
      be surrounded by a large empty surface area (>480 A2). In contrast, the CV+
      cations on a type II sites are restricted with an average angle of approximately
      40 degrees tilted off the surface normal, suggesting that the CV+ cations on
      these sites are grouped closely together. The average tilt angle increases with
      increasing concentration of crystal violet so that CV+ cations may be separated
      from each other to minimize the repulsion of nearby CV+ and SiOH sites.

PMID- 17429946
TI  - Structural evidence for a ligand coordination switch in liver alcohol
      dehydrogenase.
AB  - The use of substrate analogues as inhibitors provides a way to understand and
      manipulate enzyme function. Here we report two 1 A resolution crystal structures
      of liver alcohol dehydrogenase in complex with NADH and two inhibitors: dimethyl
      sulfoxide and isobutyramide. Both structures present a dynamic state of
      inhibition. In the dimethyl sulfoxide complex structure, the inhibitor is caught
      in transition on its way to the active site using a flash-freezing protocol and a
      cadmium-substituted enzyme. One inhibitor molecule is partly located in the first
      and partly in the second coordination sphere of the active site metal. A
      hydroxide ion bound to the active site metal lies close to the pyridine ring of
      NADH, which is puckered in a twisted boat conformation. The cadmium ion is
      coordinated by both the hydroxide ion and the inhibitor molecule, providing
      structural evidence of a coordination switch at the active site metal ion. The
      structure of the isobutyramide complex reveals the partial formation of an adduct
      between the isobutyramide inhibitor and NADH. It provides evidence of the
      contribution of a shift from the keto to the enol tautomer during aldehyde
      reduction. The different positions of the inhibitors further refine the knowledge
      of the dynamics of the enzyme mechanism and explain how the crowded active site
      can facilitate the presence of a substrate and a metal-bound hydroxide ion.

PMID- 17429947
TI  - Oxidized cholesterol metabolites found in human atherosclerotic lesions promote
      apolipoprotein C-II amyloid fibril formation.
AB  - Apolipoprotein amyloid deposits and lipid oxidation products are colocalized in
      human atherosclerotic tissue. In this study we show that the primary ozonolysis
      product of cholesterol, 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al (KA), rapidly
      promotes human apolipoprotein (apo) C-II amyloid fibril formation in vitro.
      Previous studies show that hydrophobic aldehydes, including KA, modify proteins
      by the formation of a Schiff base with the lysine epsilon-amino group or N
      terminal amino group. High-performance liquid chromatography, mass spectrometry,
      and proteolysis of KA-modified apoC-II revealed that KA randomly modified six
      different lysine residues, with primarily one KA attached per apoC-II molecule.
      Competition experiments showed that an aldehyde scavenging compound partially
      inhibited the ability of KA to hasten apoC-II fibril formation. Conversely, the
      acid derivative of KA, lacking the ability to form a Schiff base, accelerated
      apoC-II fibril formation, albeit to a lesser extent, suggesting that
      amyloidogenesis triggered by KA involves both covalent and noncovalent
      mechanisms. The viability of a noncovalent mechanism mediated by KA has been
      observed previously with alpha-synuclein aggregation, implicated in Parkinson's
      disease. Electron microscopy demonstrated that fibrils formed in the presence of
      KA had a similar morphology to native fibrils; however, the isolated KA-apoC-II
      covalent adducts in the absence of unmodified apoC-II formed fibrillar structures
      with altered ropelike morphologies. KA-mediated fibril formation by apoC-II was
      inhibited by the addition of the amine-containing compound hydralazine and the
      lipid-binding protein apoA-I. These in vitro studies suggest that the oxidized
      small molecule pool could trigger or hasten the aggregation of apoC-II to form
      amyloid deposits.

PMID- 17429949
TI  - Catalytic mechanism and product specificity of rubisco large subunit
      methyltransferase: QM/MM and MD investigations.
AB  - Molecular dynamics (MD) simulations and hybrid quantum mechanics/molecular
      mechanics (QM/MM) calculations have been carried out in an investigation of
      Rubisco large subunit methyltransferase (LSMT). It was found that the appearance
      of a water channel is required for the stepwise methylation by S
      adenosylmethionine (AdoMet). The water channel appears in the presence of AdoMet
      (LSMT.Lys-NH3+.AdoMet), but is not present immediately after methyl transfer
      (LSMT.Lys-N(Me)H2+.AdoHcy). The water channel allows proton dissociation from
      both LSMT.AdoMet.Lys-NH3+ and LSMT.AdoMet.Lys-N(Me)H2+. The water channel does
      not appear for proton dissociation from LSMT.AdoMet.Lys-N(Me)2H+, and a third
      methyl transfer does not occur. By QM/MM, the calculated free energy barrier of
      the first methyl transfer reaction catalyzed by LSMT (Lys-NH2 + AdoMet --> Lys
      N(Me)H2+ + AdoHcy) is DeltaG++ = 22.8 +/- 3.3 kcal/mol. This DeltaG++ is in
      remarkable agreement with the value 23.0 kcal/mol calculated from the
      experimental rate constant (6.2 x 10-5 s-1). The calculated DeltaG++ of the
      second methyl transfer reaction (AdoMet + Lys-N(Me)H --> AdoHcy + Lys-N(Me)2H+)
      at the QM/MM level is 20.5 +/- 3.6 kcal/mol, which is in agreement with the value
      22.0 kcal/mol calculated from the experimental rate constant (2.5 x 10-4 s-1).
      The third methyl transfer (Lys-N(Me)2 + AdoMet --> Lys-N(Me)3+ + AdoHcy) is
      associated with an allowed DeltaG++ of 25.9 +/- 3.2 kcal/mol. However, this
      reaction does not occur because a water channel does not form to allow the proton
      dissociation of Lys-N(Me)2H+. Future studies will determine whether the product
      specificity of lysine (mono, di, and tri) methyltransferases is determined by the
      formation of water channels.

PMID- 17429950
TI  - Application of a novel design paradigm to generate general nonpeptide
      combinatorial templates mimicking beta-turns: synthesis of ligands for
      melanocortin receptors.
AB  - We report the further application of a novel approach to template and ligand
      design by the synthesis of agonists of the melanocortin receptor. This design
      method uses the conserved structural data from the three-dimensional
      conformations of beta-turn peptides to design rigid nonpeptide templates that
      mimic the orientation of the main chain C-alpha atoms in a peptide beta-turn. We
      report details on a new synthesis of derivatives of template 1 that are useful
      for the synthesis of exploratory libraries. The utility of this technique is
      further exemplified by several iterative rounds of high-throughput synthesis and
      screening, which result in new partially optimized nonpeptide agonists for
      several melanocortin receptors.

PMID- 17429951
TI  - YinYang atom: a simple combined ab initio quantum mechanical molecular mechanical
      model.
AB  - A simple interface is proposed for combined quantum mechanical (QM) molecular
      mechanical (MM) calculations for the systems where the QM and MM regions are
      connected through covalent bonds. Within this model, the atom that connects the
      two regions, called YinYang atom here, serves as an ordinary MM atom to other MM
      atoms and as a hydrogen-like atom to other QM atoms. Only one new empirical
      parameter is introduced to adjust the length of the connecting bond and is
      calibrated with the molecule propanol. This model is tested with the computation
      of equilibrium geometries and protonation energies for dozens of molecules.
      Special attention is paid on the influence of MM point charges on optimized
      geometry and protonation energy, and it is found that it is important to maintain
      local charge-neutrality in the MM region in order for the accurate calculation of
      the protonation and deprotonation energies. Overall the simple YinYang atom model
      yields comparable results to some other QM/MM models.

PMID- 17429952
TI  - Resonance-assisted hydrogen bonds: a critical examination. Structure and
      stability of the enols of beta-diketones and beta-enaminones.
AB  - The characteristics of the intramolecular hydrogen bond (IMHB) for a series of 40
      different enols of beta-diketones and their nitrogen counterparts have been
      systematically analyzed at the B3LYP/6-311+G(3df,2p)//B3LYP/6-311+G(d,p) level of
      theory. In some cases, two tautomers may exist which are interconnected by a
      hydrogen shift through the IMHB. In tautomer a the HB donor group (YH) is
      attached to the six-membered ring, while in tautomer b the HB acceptor (X) is the
      one that is attached to the six-membered ring. We found that changing an O to a N
      favors the a tautomer when the atom is endo and the contrary when it is exo,
      while the presence of a double bond favors the a tautomers. As expected, the OH
      group behaves as a better HB donor than the NH2 group and the C=NH group as a
      better HB acceptor than the C=O group, although the first effect clearly
      dominates. Accordingly, the expected IMHB strength follows the [donor, acceptor]
      trend: [OH, C=NH] > [OH, C=O] > [NH2, C=NH] > [NH2, C=O]. For all those compounds
      in which the functionality exhibiting the IMHB is unsaturated (I-type), the IMHB
      is much stronger than in their saturated counterparts (II-type). However, when
      the systems of the II-type subset, which are saturated, are constrained to have
      the HB donor and the HB acceptor lying in the same plane and at the same distance
      as in the corresponding unsaturated analogue, the IMHB is of similar or even
      larger strength. Hence, we conclude that, at least for this series of unsaturated
      compounds, the resonance-assisted hydrogen bond effect is not the primary reason
      behind the strength of their IMHBs, which is simply a consequence of the
      structure of the sigma-skeleton of the system that keeps the HB donor and the HB
      acceptor coplanar and closer to each other.

PMID- 17429948
TI  - Purification and characterization of the FeII- and alpha-ketoglutarate-dependent
      xanthine hydroxylase from Aspergillus nidulans.
AB  - His6-tagged xanthine/alpha-ketoglutarate (alphaKG) dioxygenase (XanA) of
      Aspergillus nidulans was purified from both the fungal mycelium and recombinant
      Escherichia coli cells, and the properties of the two forms of the protein were
      compared. Evidence was obtained for both N- and O-linked glycosylation on the
      fungus-derived XanA, which aggregates into an apparent dodecamer, while bacterium
      derived XanA is free of glycosylation and behaves as a monomer. Immunological
      methods identify phosphothreonine in both forms of XanA, with phosphoserine also
      detected in the bacterium-derived protein. Mass spectrometric analysis confirms
      glycosylation and phosphorylation of the fungus-derived sample, which also
      undergoes extensive truncation at its amino terminus. Despite the major
      differences in the properties of these proteins, their kinetic parameters are
      similar (kcat = 30-70 s-1, Km of alphaKG = 31-50 muM, Km of xanthine
      approximately 45 muM, and pH optima at 7.0-7.4). The enzyme exhibits no
      significant isotope effect when [8-2H]xanthine is used; however, it demonstrates
      a 2-fold solvent deuterium isotope effect. CuII and ZnII potently inhibit the
      FeII-specific enzyme, whereas CoII, MnII, and NiII are weaker inhibitors. NaCl
      decreases the kcat and increases the Km of both alphaKG and xanthine. The alphaKG
      cosubstrate can be substituted with alpha-ketoadipate (9-fold decrease in kcat
      and 5-fold increase in the Km compared to those of the normal alpha-keto acid),
      while the alphaKG analogue N-oxalylglycine is a competitive inhibitor (Ki = 0.12
      muM). No alternative purines effectively substitute for xanthine as a substrate,
      and only one purine analogue (6,8-dihydroxypurine) results in significant
      inhibition. Quenching of the endogenous fluorescence of the two enzyme forms by
      xanthine, alphaKG, and DHP was used to characterize their binding properties. A
      XanA homology model was generated on the basis of the structure of the related
      enzyme TauD (PDB entry 1OS7) and provided insights into the sites of
      posttranslational modification and substrate binding. These studies represent the
      first biochemical characterization of purified xanthine/alphaKG dioxygenase.

PMID- 17429953
TI  - Comparison of geometric, electronic, and vibrational properties for isomers of
      small fullerenes C20-C36.
AB  - We employ the self-consistent-charge density-functional tight-binding (SCC-DFTB)
      method for computing geometric, electronic, and vibrational properties for
      various topological isomers of small fullerenes. We consider all 35 five- and six
      member rings containing isomers of small fullerenes, C20, C24, C26, C28, C30,
      C32, C34, and C36, as first part of a larger effort to catalog CC distance
      distributions, valence CCC angle distributions, electronic densities of states
      (DOSs), vibrational densities of states (VDOSs), and infrared (IR) and Raman
      spectra for fullerenes C20-C180. Common features among the fullerenes are
      identified and properties characteristic for each specific fullerene isomer are
      discussed.

PMID- 17429954
TI  - Understanding of assembly phenomena by aromatic-aromatic interactions: benzene
      dimer and the substituted systems.
AB  - Interactions involving aromatic rings are important in molecular/biomolecular
      assembly and engineering. As a consequence, there have been a number of
      investigations on dimers involving benzene or other substituted pi systems. In
      this Feature Article, we examine the relevance of the magnitudes of their
      attractive and repulsive interaction energy components in governing the
      geometries of several pi-pi systems. The geometries and the associated binding
      energies were evaluated at the complete basis set (CBS) limit of coupled cluster
      theory with singles, doubles, and perturbative triples excitations [CCSD(T)]
      using a least biased scheme for the given data set. The results for the benzene
      dimer indicate that the floppy T-shaped structure (center-to-center distance:
      4.96 A, with an axial benzene off-centered above the facial benzene) is
      isoenergetic in zero-point-energy (ZPE) corrected binding energy (D0) to the
      displaced-stacked structure (vertical interplanar distance: 3.54 A). However, the
      T-shaped structure is likely to be slightly more stable (D0 approximately equal
      to 2.4-2.5 kcal/mol) if quadruple excitations are included in the coupled cluster
      calculations. The presence of substituents on the aromatic ring, irrespective of
      their electron withdrawing or donating nature, leads to an increase in the
      binding energy, and the displaced-stacked conformations are more stabilized than
      the T-shaped conformers. This explains the wide prevalence of displaced stacked
      structures in organic crystals. Despite that the dispersion energy is dominating,
      the substituent as well as the conformational effects are correlated to the
      electrostatic interaction. This electrostatic origin implies that the substituent
      effect would be reduced in polar solution, but important in apolar media, in
      particular, for assembling processes.

PMID- 17429955
TI  - Temperature effect on the absorption spectrum of the hydrated electron paired
      with a lithium cation in deuterated water.
AB  - The absorption spectra of the hydrated electron in 1.0 to 4.0 M LiCl or LiClO4
      deuterated water solutions were measured by pulse radiolysis techniques from room
      temperature to 300 degrees C at a constant pressure of 25 MPa. The results show
      that when the temperature is increased and the density is decreased, the
      absorption spectrum of the electron in the presence of a lithium cation is
      shifted to lower energies. Quantum classical molecular dynamics (QCMD)
      simulations of an excess electron in bulk water and in the presence of a lithium
      cation have been performed to compare with the experimental results. According to
      the QCMD simulations, the change in the shape of the spectrum is due to one of
      the three p-like excited states of the solvated electron destabilized by core
      repulsion. The study of s --> p transition energies for the three p-excited
      states reveals that for temperatures higher than room temperature, there is a
      broadening of each individual s --> p absorption band due to a less structured
      water solvation shell.

PMID- 17429956
TI  - Theoretical study of the dynamics of AR collisions with C2H6 and C2F6 at
      hyperthermal energy.
AB  - We present a classical-trajectory study of the dynamics of high-energy (5-12 eV)
      collisions between Ar atoms and the C2H6 and C2F6 molecules. We have constructed
      the potential-energy surfaces for these systems considering separately the Ar
      molecule interactions (intermolecular potential) and the interactions within the
      molecule (intramolecular potential). The intermolecular surfaces consist of
      pairwise empirical potentials derived from high-accuracy ab initio calculations.
      The intramolecular potentials for C2H6 and C2F6 are described using specific
      reaction-parameters semiempirical Hamiltonians and are calculated "on the fly",
      i.e., while the trajectories are evolving. Trajectory analysis shows that C2F6
      absorbs more energy than C2H6 and is more susceptible to collision-induced
      dissociation (CID). C-C bond-breakage processes are more important than C-H or C
      F bond breakage at the energies explored in this work. Analysis of the reaction
      mechanism for CID processes indicates that, although C-C breakage is mostly
      produced by side-on collisions, head-on collisions are more efficient in
      producing C-F or C-H dissociation. Our results suggest that high-energy
      collisions between closed-shell species of the natural low-Earth-orbit
      environment and spacecraft can contribute to the observed degradation of polymers
      that coat spacecraft surfaces.

PMID- 17429957
TI  - Molecular recognition of DNA by rigid [N]-polynorbornane-derived bifunctional
      intercalators: synthesis and evaluation of their binding properties.
AB  - We have exploited the concept of multivalency in the context of DNA recognition,
      using novel chemistry to synthesize a new type of bis-intercalator with unusual
      sequence-selectivity. Bis-intercalation has been observed previously, but design
      principles for de novo construction of such molecules are not known. Our
      compounds feature two aromatic moieties projecting from a rigid, polynorbornane
      based scaffold. The length and character of the backbone as well as the identity
      of the intercalators were varied, resulting in mono- or divalent recognition of
      the double helix with varying affinity. Our lead compound proved to be a
      moderately sequence-selective bis-intercalator with an unwinding angle of 27
      degrees and a binding constant of about 8 microM. 9-aminoacridine rings were
      preferred over acridine carboxamides or naphthalimides, and a rigid [3]
      polynorbornane scaffold was superior to a [5]-polynorbornane. The flexibility of
      the linker connecting the rings to the scaffold, although less influential, could
      affect the strength and character of the DNA binding.

PMID- 17429958
TI  - Facile and efficient synthesis of C-hydroxycarboranes and C,C'
      dihydroxycarboranes.
AB  - C-Hydroxylated carboranes, carboranols, have interesting properties resulting
      from their hydroxyl protons being highly acidic because of the electron-deficient
      nature of the carborane cage. We described here an efficient synthesis of C
      hydroxycarboranes 2 and C,C'-dihydroxycarboranes 3 by the reaction of carboranyl
      lithium and trimethylborate, followed by oxidation with hydrogen peroxide in the
      presence of acetic acid, to afford the corresponding o-, m-, and p
      hydroxycarboranes 2 and o-, m-, and p-dihydroxycarboranes 3 selectively in high
      yields through a one-pot procedure. The m- and p-carborane isomers of 2 and 3
      were obtained in especially good yields (2b, 85%; 2c, 85%; 3b, 95%; 3c, 96%). DFT
      calculations were performed on the dihydroxycarboranes 3 to compare the
      geometrical features of the isomers at the same level of theory and to
      characterize their electronic and NMR spectroscopic (13C chemical shift)
      properties.

PMID- 17429959
TI  - Complexation kinetics of copper(II) and nickel(II) with macrocycles:
      identification of an outer-sphere chelate effect.
AB  - Ligand-protonation constants and complexation kinetics of differently protonated
      forms of 10-methyl-1,4,8,12-tetraazacyclopentadecan-10-amine, 1,4,8,12
      tetraazacyclopentadecane, and 1,4,8,12-tetraazacyclopentadecan-10-carboxylic acid
      with Cu(II) and Ni(II) in aqueous solution have been determined. These results
      are combined with a wide range of published complexation rate constants of
      partially protonated macrocyclic ligands with the same metal ions. Insight is
      gained into the electrostatic effects and the outer-sphere interaction of
      partially protonated ligands with aquated metal ions. An outer-sphere chelate
      effect has been ascertained.

PMID- 17429960
TI  - Phosphorescent iridium complexes based on 2-phenylimidazo[1,2-a]pyridine ligands:
      tuning of emission color toward the blue region and application to polymer light
      emitting devices.
AB  - A series of new blue-phosphorescent iridium(III) complexes 1-14 with ligands of 2
      phenylimidazo[1,2-a]pyridine (pip) derivatives were successfully prepared, and
      their electrochemical, photophysical, and electroluminescent (EL) properties were
      systematically investigated. It was found that the emission maxima are
      significantly dependent on the substituents on the phenyl ring in the range of
      489-550 nm. For instance, electron-withdrawing groups such as F and CF3 shift the
      emission maxima to shorter wavelengths by lowering the HOMO levels (complexes 4
      8), whereas the extended pi-conjugation leads to bathochromic shifts (2, 3). To
      obtain further information about the frontier orbital, substitution effects on
      the imidazole part were also investigated here, and it was found that electron
      withdrawing or -donating substituents on the imidazole ring affected the emission
      maxima (9, 557 nm; 10, 525 nm). These results including their oxidation
      potentials suggest that the HOMO of the pip-based complex is a mixture of Ir-d,
      phenyl-pi, and imidazole-pi orbitals. From this viewpoint, combination of
      electron-withdrawing substituents on the phenyl ring with the use of another
      ancillary ligand enabled further blue shifts (13, 468, 499 nm; 14, 464, 494 nm).
      This new system based on pip is one of the rare examples of iridium complexes
      whose emissions can be tuned to the blue region. Preliminary polymer light
      emitting devices (PLEDs) employing the Ir complexes were fabricated, and the
      devices showed moderate EL efficiencies.

PMID- 17429961
TI  - Synthesis, structure, and luminescence of di- and trinuclear palladium/gold and
      platinum/gold complexes with (2,7-di-tert-butylfluoren-9
      ylidene)methanedithiolate.
AB  - Acetone solutions of [Au(OClO3)(PCy3)] react with complexes [M{S2C=(t-Bu-fy)}2]2-
      [t-Bu-fy=2,7-di-tert-butylfluoren-9-ylidene; M=Pd (2a), Pt (2b)] or [M{S2C=(t-Bu
      fy)}(dbbpy)] [dbbpy=4,4'-di-tert-butyl-2,2'-bipyridyl; M=Pd (3a), Pt (3b)] to
      give the heteronuclear complexes [M{S2C=(t-Bu-fy)}2{Au(PCy3)}2] [2:1 molar ratio;
      M=Pd (4a), Pt (4b)], [M{S2C=(t-Bu-fy)}(dbbpy){Au(PCy3)}]ClO4 [1:1 molar ratio;
      M=Pd (5a), Pt (5b)], or [M{S2C=(t-Bu-fy)}(dbbpy){Au(PCy3)}2](ClO4)2 [2:1 molar
      ratio; M=Pd (6a), Pt (6b)]. The crystal structures of 3a, 4a, 4b, 5b, and 6a have
      been solved by single-crystal X-ray studies and, in the cases of the
      heteronuclear derivatives, reveal the formation of short Pd...Au or Pt...Au
      metallophilic contacts in the range of 3.048-3.311 A. Compounds 4a and b and 5a
      and b undergo a dynamic process in solution that involves the migration of the
      [Au(PCy3)]+ units between the sulfur atoms of the dithiolato ligands. The
      coordination of 2a and b and 3a and b to [Au(PCy3)]+ units results in important
      modifications of their photophysical properties. The dominant effect in the
      absorption spectra is an increase in the energy of the MLCT (4a and b) or charge
      transfer to diimine (5a, b, 6a, b) transitions because of a decrease in the
      energies of the mixed metal/dithiolate HOMOs. The Pd complexes 2a and 4a are
      luminescent at 77 K, and the features of their emissions are consistent with an
      essentially metal-centered 3d-d state. The Pt/Au complexes are also luminescent
      at 77 K, and their emissions can be assigned as originating from a MLCT triplet
      state (4b) or a mixture of charge transfer to diimine and diimine intraligand pi
      pi* triplet states (5b and 6b).

PMID- 17429962
TI  - Optical memory and multistep luminescence thermochromism in single crystals of
      K2Na[Ag(CN)2]3.
AB  - Single crystals of the layered compound K2Na[Ag(CN)2]3 exhibit a dual emission
      with high-energy (HE) and low-energy (LE) phosphorescence bands at 313 and 402
      nm, respectively. Remarkably, the crystals exhibit "optical memory", in which a
      new emission band with intermediate energy (IE) at 380 nm is generated upon laser
      irradiation (lambda ex = 266 nm) at cryogenic temperatures. The irradiated
      crystals reinstate their original luminescence spectrum upon heating to room
      temperature and then recooling. In addition to these unusual "write/read/erase"
      changes, the crystals also exhibit multistep luminescence thermochromism such
      that the LE/HE intensity ratio increases between 17 and 80 K but then decreases
      upon further heating. The unprecedented occurrence of both novel phenomena in one
      compound has been related to reversible photophysical changes instead of
      irreversible photochemical changes.

PMID- 17429964
TI  - Operationally unsaturated pincer/rhenium complexes form metal carbenes from
      cycloalkenes and metal carbynes from alkanes.
AB  - Operationally unsaturated (i.e., 16/18-electron) (PNPR)Re(H)4, where PNPR is
      N(SiMe2CH2PR2)2, is reactive at 22 degrees C with cyclic olefins. The first
      observed products are generally (PNPR)Re(H)2(cycloalkylidene), with hydrogenated
      olefin as the product of hydrogen abstraction from the tetrahydride. The
      tetrahydride complex with R = tBu generally fails to react (too bulky), that with
      R = cyclohexyl suffers a (controllable) tendency to abstraction of 3H from one
      ring, forming an eta3-cyclohexenyl compound, and that with R = iPr generally
      gives the richest bimolecular reactivity. The cyclic monoolefins studied show
      distinct reactivity, C6 giving first the carbene and then coordinated
      cyclohexadiene, C5 giving carbene, then diene, and then eta5-C5H5, C8 giving
      carbene and then eta2-cyclooctyne, and C12 giving an eta3-allyl. Norbornene gives
      a pi-complex of the norbornene in thermal equilibrium with its carbene isomer; at
      90 degrees C, hydrocarbon ligand Calpha-Cbeta bond cleavage occurs to give, for
      the first time, a carbyne complex from an internal olefin. Two compounds
      synthesized here have the formal composition "(PNPR)Re + olefin", and each of
      these is capable of dehydrogenating the methyl group of a variety of alkanes at
      110 degrees C to form (PNP)ReH triple bond (CR).

PMID- 17429965
TI  - Understanding a mechanism of organic cosolvent inactivation in heme monooxygenase
      P450 BM-3.

PMID- 17429966
TI  - Mechanistic evidence for a ring-opening pathway in the Pd-catalyzed direct
      arylation of benzoxazoles.

PMID- 17429967
TI  - Correlation of protein structure and dynamics to scalar couplings across hydrogen
      bonds.
AB  - NMR-observable scalar couplings across hydrogen bonds in nucleic acids and
      proteins present a quantitative measure for the geometry and--by the implicit
      experimental time averaging--dynamics of hydrogen bonds. We have carried out in
      depth molecular dynamics (MD) simulations with various force fields on three
      proteins: ubiquitin, the GB1 domain of protein G, and the SMN Tudor domain, for
      which experimental h3JNC' scalar couplings of backbone hydrogen bonds and various
      high-resolution X-ray structures are available. Theoretical average values for
      h3JNC' were calculated from the snapshots of these MD simulations either by
      density functional theory or by a geometric parametrization (Barfield, M. J. Am.
      Chem. Soc. 2002, 124, 4158-4168). No significant difference was found between the
      two methods. The results indicate that time-averaging using explicit water
      solvation in the MD simulations improves significantly the agreement between
      experimental and theoretical values for the lower resolution structures ubiquitin
      (1.8 A), Tudor domain (1.8 A), and protein G (2.1 A). Only marginal improvement
      is found for the high-resolution structure (1.1 A) of protein G. Hence,
      experimental h3JNC' values are compatible with a static, high-resolution
      structural model. The MD averaging of the low-resolution structures moves the
      averages of the rHO distance and the H...O=C angle theta closer to their
      respective values in the high-resolution structures, thereby improving the
      agreement using experimental h3JNC' data. In contrast, MD averaging with implicit
      water models deteriorates the agreement with experiment for all proteins. The
      differing behavior can be explained by an artifactual lengthening of H-bonds
      caused by the implicit water models.

PMID- 17429968
TI  - Unambiguous evidence for efficient chemical catalysis of adenosine ester
      aminolysis by its 2'/3'-OH.

PMID- 17429969
TI  - Design of liquid-crystalline aqueous suspensions of rutile nanorods: evidence of
      anisotropic photocatalytic properties.
AB  - TiO2 rutile nanorods of average length L = 160 +/- 40 nm and average diameter D =
      15 +/- 5 nm have been synthesized through a seed-mediated growth process by TiCl4
      hydrolysis in concentrated acidic solution. These nanorods were dispersed in
      water to yield stable (aggregation-free) colloidal aqueous suspensions. At volume
      fractions phi > 3%, the suspensions spontaneously display a phase separation into
      an isotropic liquid phase and a liquid-crystalline phase identified as nematic by
      X-ray scattering. At phi > 12%, the suspensions form a nematic single phase, with
      large order parameter, S = 0.75 +/- 0.05. Very well aligned rutile films on glass
      substrate were produced by spin-coating, and their photocatalytic properties were
      examined by monitoring the decomposition of methylene blue under UV light. We
      found that UV-light polarized along the quadratic axis of the rutile nanorods was
      most efficient for this photocatalytic reaction.

PMID- 17429970
TI  - Valence tautomerism and coordinative lability in copper(II)-imidazolyl
      semiquinonate anion radical models for the CuB center in cytochrome c oxidases.

PMID- 17429971
TI  - Turn-on and ratiometric mercury sensing in water with a red-emitting probe.
AB  - The synthesis, photophysical properties, and Hg(II) binding of a red-emitting
      sensor for mercuric ion are presented. 2-[11-[(2-[[Bis-(2
      ethylsulfanylethyl)amino]methyl]phenylamino)methyl]-3-hydroxy-10-oxo-10H
      benzo[c]xanthen-7-yl]benzoic acid (MS5) is based on the seminaphthofluorescein
      chromophore and employs a thioether-rich metal-binding unit. This sensor affords
      both turn-on and single-excitation dual-emission ratiometric Hg(II) detection in
      aqueous solution. The fluorescence response of MS5 is Hg(II)-specific, and the
      probe is selective for Hg(II) over alkali and alkaline earth metals, most
      divalent first-row transition metal ions, and the Group 12 congeners Zn(II) and
      Cd(II). MS5 binds Hg(II) reversibly and can be recycled. The EC50 for 1 microM
      MS5 is 910 nM, and a lower detection limit of 50 nM is obtained when employing
      500 nM probe. X-ray crystallographic studies using a salicylaldehyde-based model
      of MS5 are also presented. 2-[(2-[[Bis-(2
      ethylsulfanylethyl)amine]methyl]phenylamine)methyl]phenol coordinates Hg(II) with
      two thioether sulfur atoms, two amino nitrogen atoms, and a phenol oxygen atom
      arranged in a distorted trigonal bipyramidal geometry. Studies of natural water
      samples spiked with mercuric salts indicate that MS5 can rapidly detect Hg(II) in
      such complex solutions and demonstrate its potential utility in the field.

PMID- 17429974
TI  - Selective ruthenium-catalyzed transformations of enynes with diazoalkanes into
      alkenylbicyclo[3.1.0]hexanes.
AB  - Reaction of a variety of CCH bond-containing 1,6-enynes with N2CHSiMe3 in the
      presence of RuCl(COD)Cp* as catalyst precursor leads, at room temperature, to the
      general formation of alkenylbicyclo[3.1.0]hexanes with high Z-stereoselectivity
      of the alkenyl group and cis arrangement of the alkenyl group and an initial
      double-bond substituent, for an E-configuration of this double bond. The
      stereochemistry is established by determining the X-ray structures of three
      bicyclic products. The same reaction with 1,6-enynes bearing an R substituent on
      the C1 carbon of the triple bond results in either cyclopropanation of the double
      bond with bulky R groups (SiMe3, Ph) or formation of alkylidene-alkenyl five
      membered heterocycles, resulting from a beta elimination process, with less bulky
      R groups (R = Me, CH2CH=CH2). The reaction can be applied to in situ desilylation
      in methanol and direct formation of vinylbicyclo[3.1.0]hexanes and to the
      formation of some alkenylbicyclo[4.1.0]heptanes from 1,7-enynes. The catalytic
      formation of alkenylbicyclo[3.1.0]hexanes also takes place with enynes and
      N2CHCO2Et or N2CHPh. The reaction can be understood to proceed by an initial
      [2+2] addition of the Ru=CHSiMe3 bond with the enyne CCH bond, successively
      leading to an alkenylruthenium-carbene and a key alkenyl bicyclic
      ruthenacyclobutane, which promotes the cyclopropanation, rather than metathesis,
      into bicyclo[3.1.0]hexanes. Density functional theory calculations performed
      starting from the model system Ru(HCCH)(CH2=CH2)Cl(C5H5) show that the
      transformation into a ruthenacyclobutane intermediate occurs with a temporary
      eta3-coordination of the cyclopentadienyl ligand. This step is followed by
      coordination of the alkenyl group, which leads to a mixed alkyl-allyl ligand.
      Because of the non-equivalence of the terminal allylic carbon atoms, their
      coupling favors cyclopropanation rather than the expected metathesis process. A
      direct comparison of the energy profiles with respect to those involving the
      Grubbs catalyst is presented, showing that cyclopropanation is favored with
      respect to enyne metathesis.

PMID- 17429972
TI  - Intramolecular single-turnover reaction in a cytochrome C oxidase model bearing a
      Tyr244 mimic.

PMID- 17429973
TI  - GM1 clustering inhibits cholera toxin binding in supported phospholipid
      membranes.
AB  - The present studies explore multivalent ligand-receptor interactions between
      pentameric cholera toxin B subunits (CTB) and the corresponding membrane ligand,
      ganglioside GM1. CTB binding was monitored on supported phospholipid bilayers
      coated on the walls and floors of microfluidic channels. Measurements were made
      by total internal reflection fluorescence microscopy (TIRFM). Apparent
      dissociation constants were extracted by fitting the binding data to both the
      Hill-Waud and Langmuir adsorption isotherm equations. Studies of the effect of
      ligand density on multivalent CTB-GM1 interactions revealed that binding weakened
      with increasing GM1 density from 0.02 mol % to 10.0 mol %. Such a result could be
      explained by the clustering of GM1 on the supported phospholipid membranes, which
      in turn inhibited the binding of CTB. Atomic force microscopy (AFM) experiments
      directly verified GM1 clustering within the supported POPC bilayers.

PMID- 17429975
TI  - Unexpected C=C bond formation via doubly dehydrogenative coupling of two
      saturated sp3 C-H bonds activated with a polymolybdate.

PMID- 17429976
TI  - Helical pores self-assembled from homochiral dendritic dipeptides based on L-Tyr
      and nonpolar alpha-amino acids.
AB  - The synthesis of dendritic dipeptides (4-3,4-3,5)12G2-CH2-Boc-L-Tyr-X-OMe where X
      = Gly, L-Val, L-Leu, L-Ile, L-Phe, and L-Pro is reported. Their self-assembly in
      bulk and in solution and the structural and retrostructural analysis of their
      periodic assemblies were compared to those of the previously reported and
      currently reinvestigated dendritic dipeptides with X = L-Ala. All dendritic
      dipeptides containing as X nonpolar alpha-amino acids self-assemble into helical
      porous columns. The substituent of X programs the structure of the helical pore
      and the resulting periodic array, in spite of the fact that its molar mass
      represents only between 0.05 and 4.77% from the molar mass of the dendritic
      dipeptide. In addition to the various 2-D columnar lattices, the dendritic
      dipeptides based on L-Ala, L-Leu, and L-Phe self-organize into 3-D hexagonal
      columnar crystals while those based on L-Val and L-Ile into an unknown columnar
      crystal. The principles via which the aliphatic and aromatic substituents of X
      program the structure of the helical pores indicate synthetic pathways to helical
      pores with bioinspired functions based on artificial nonpolar alpha-amino acids.

PMID- 17429977
TI  - Mild and efficient pentafluorophenylammonium triflate (PFPAT)-catalyzed C
      acylations of enol silyl ethers or ketene silyl (Thio)acetals with acid
      chlorides.
AB  - A pentafluorophenylammonium triflate (PFPAT) catalyst (5 mol %) successfully
      promoted C-acylation of enol silyl ethers with acid chloride to produce various
      beta-diketones (12 examples; 62-92% yield). Similarly, C-acylation of ketene
      silyl acetals or ketene silyl thioacetals (i.e., crossed Claisen condensation)
      proceeded smoothly to provide not only alpha-monoalkylated beta-keto (thio)esters
      but also thermodynamically unfavorable (less accessible) alpha,alpha-dialkylated
      beta-keto (thio)esters in good to excellent yield (38 examples; 60-92% yield).

PMID- 17429978
TI  - Stereocontrolled synthesis of (-)-galanthamine.
AB  - An enantioselective synthesis of (-)-galanthamine has been realized in 11 linear
      steps starting from isovanillin. A Mitsunobu aryl ether forming reaction was used
      to assemble the galanthamine backbone, which was stitched together using enyne
      ring-closing metathesis, Heck, and N-alkylation reactions affording the
      tetracyclic ring system. Control of relative and absolute stereochemistry was
      derived from an easily accessible enantiomerically enriched propargylic alcohol
      13.

PMID- 17429979
TI  - Colorimetric sensor for ATP in aqueous solution.
AB  - A new chromogenic complex 1.Zn has been synthesized, and its interactions with
      different biologically important phosphates have been investigated in aqueous
      solution (pH approximately 7.2). A visual color change can be detected on binding
      of ATP to 1.Zn, whereas no such change is observed when other biologically
      related anions (AMP, ADP, PPi, or Phosphate) are used. Complex 1.Zn can also be
      used as a staining agent for yeast cells allowing detection under normal light
      microscopy.

PMID- 17429980
TI  - Double phosphorylation of the myosin regulatory light chain during rigor mortis
      of bovine Longissimus muscle.
AB  - To investigate changes in myosin light chains (MyLCs) during postmortem aging of
      the bovine longissimus muscle, we performed two-dimensional gel electrophoresis
      followed by identification with matrix-assisted laser desorption ionization time
      of-flight mass spectrometry. The results of fluorescent differential gel
      electrophoresis showed that two spots of the myosin regulatory light chain
      (MyLC2) at pI values of 4.6 and 4.7 shifted toward those at pI values of 4.5 and
      4.6, respectively, by 24 h postmortem when rigor mortis was completed. Meanwhile,
      the MyLC1 and MyLC3 spots did not change during the 14 days postmortem.
      Phosphoprotein-specific staining of the gels demonstrated that the MyLC2 proteins
      at pI values of 4.5 and 4.6 were phosphorylated. Furthermore, possible N-terminal
      region peptides containing one and two phosphoserine residues were detected in
      each mass spectrum of the MyLC2 spots at pI values of 4.5 and 4.6, respectively.
      These results demonstrated that MyLC2 became doubly phosphorylated during rigor
      formation of the bovine longissimus, suggesting involvement of the MyLC2
      phosphorylation in the progress of beef rigor mortis. KEYWORDS: Bovine; myosin
      regulatory light chain (RLC, MyLC2); phosphorylation; rigor mortis; skeletal
      muscle.

PMID- 17429981
TI  - Quantitative determination of diuron in ground and surface water by time-resolved
      fluoroimmunoassay: seasonal variations of diuron, carbofuran, and paraquat in an
      agricultural area.
AB  - The aim of this research is to develop an ultrasensitive time-resolved
      fluorescence immunoassay (TR-FIA) for herbicide diuron in water samples. This
      method appears to be a promising approach, instead of conventional analytical
      techniques, in the screening procedure of organic pollutants because it is
      simple, rapid, and specific, and it does not require sample preconcentration or
      cleanup. Lanthanide chelate used as label allows to achieve sensitivity even 10
      times higher than most of the other techniques. It has been applied to monitoring
      diuron contamination in specimens collected along a year in an agricultural area.
      The water specimens were collected monthly from lake, well, and irrigation ditch
      in the agricultural area south of Milan. Assay was performed using diuron
      specific polyclonal antibody raised in sheep; as fluorescent marker, we used
      rabbit antisheep IgG conjugated with a chelating molecule complexed with Eu3+.
      The compound 4-(3-(3,4-dichloro-phenyl)-1-methyl-ureido)-butyric acid (CPD) was
      synthesized and conjugated with bovine serum albumin (BSA) to prepare a solid
      phase. Sensitivity achieved was 20 ng L-1 below the European Community limits.
      Paraquat (PQ) and carbofuran (CF) presence in the same samples has been also
      evaluated in a similar way, using immunoassays with time-resolved revelation
      systems. Diuron concentration shows a peak coinciding with a peak of carbofuran
      during summer periods. The peak of diuron was 65 pg/mL in June and 180 pg/mL in
      September in ditch and lake water samples, respectively; carbofuran concentration
      was higher than diuron in all samples: a carbofuran peak was revealed in
      September and October resulting in 87 ng/mL. Herbicide paraquat was not
      detectable in any assayed sample.

PMID- 17429982
TI  - Simultaneous determination of trace levels of 10 quinolones in swine, chicken,
      and shrimp muscle tissues using HPLC with programmable fluorescence detection.
AB  - A HPLC method using a modified sample preparation procedure was optimized and
      validated for the quantification of 10 quinolones (QNs), including marbofloxacin,
      ciprofloxacin, norfloxacin, lomefloxacin, danofloxacin, enrofloxacin,
      sarafloxacin, difloxacin, oxolinic acid, and flumequine, in swine, chicken, and
      shrimp tissues. In this method, only a small mass (<or=2.0 g) of sample and a
      relatively small volume of organic reagent (<or=4.6 mL) of a nonchlorinated
      extraction solvent were required. The QNs were analyzed by liquid chromatography
      in a single run using a gradient elution program and with a programmable
      fluorescence detector to obtain optimum detection wavelengths. Mean recoveries of
      10 drugs from edible animal tissues at a concentration range of 1-100 ng g-1 were
      72.8-106.8% with relative standard deviations below 11.2%. The limits of
      quantification for each QN in different muscle tissues ranged from 0.3 to 1.0 ng
      g-1, which were below the lowest maximum residue limits (10 ng g-1) established
      in many countries. The method was also applied to the measurement of QN residues
      in commercial muscle samples. The results showed it was rapid, simple, sensitive,
      and suitable for use in food surveillance programs.

PMID- 17429983
TI  - Evaluation of enhanced hygroscopicity, bifidogenicity, and anticariogenicity of
      enzymatically synthesized beta-galactosyl-trehalose oligosaccharides.
AB  - beta-Galactosyl-trehalose oligosaccharides (beta-GTOs) were enzymatically
      prepared as a mixture of 6-beta-galactosyl-trehalose (1) and 4-beta-galactosyl
      trehalose (2) with a 9:1 ratio (w/w). The beta-GTO mixture showed a highly
      enhanced hygroscopicity as compared to those of trehalose and other sugars used.
      At 72 h of incubation under 90% relative humidity and room temperature, it had a
      large increase in weight due to its moisture absorption, which was five times
      larger than that of trehalose, 1.9 times larger than that of sucrose, and 1.5
      times larger than that of maltotriose. It was very effective in the growth
      promotion of Bifidobacteria, such as Bifidobacterium longum and Bifidobacterium
      bifidum, which was better than the growth promotion in the cases of trehalose and
      galactooligosaccharide. It also showed a highly anticariogenic property; it had
      only 10% cell proliferation of Streptococcus sobrinus for that of the sucrose
      control and 60% inhibition of insoluble glucan synthesis. Its effectiveness of
      inhibition was two and 1.5 times better than that of trehalose and one and two
      times than xylitol, respectively, against cell growth and glucan synthesis.
      Conclusively, the functionality of the beta-GTO in terms of hygroscopicity,
      bifidogenicity, and anticariogenicity was considerably improved as compared to
      that of trehalose. It is thus suggested that the beta-GTO might be applied as an
      effective humectant and prebiotic substitute with enhanced noncariogenicity in
      food applications.

PMID- 17429984
TI  - Modifications of strawberry fruit antioxidant pools and fruit quality under NaCl
      stress.
AB  - The responses of fruit antioxidants in two strawberry cultivars differing in
      their sensitivity to NaCl stress were studied. The sensitive cv. Elsanta and the
      less sensitive cv. Korona were treated with NaCl solutions of 40 and 80 mmol/L in
      the nutrient solution. In general, moderate salinity resulted in increases of
      antioxidant capacity. In cv. Korona, salt stress increased the activity of
      superoxide dismutase and the contents of glutathione, phenols, and anthocyanins,
      while that of ascorbic acid decreased. In cv. Elsanta, changes of superoxid
      dismutase activity and of ascorbic acid concentration were comparable to those of
      cv. Korona, but the decrease of ascorbic acid was more distinct. The contents of
      anthocyanins decreased, and those of phenols remained similar. The glutathione
      content was reduced at the highest NaCl level. The results indicate that less
      salt-sensitive strawberry cultivars may be grown under moderate salinity stress
      to optimize fruit quality.

PMID- 17429985
TI  - Computational study of urea and its homologue glycinamide: conformations,
      rotational barriers, and relative interactions with sodium chloride.
AB  - Conformational behaviors of urea and glycinamide have been investigated using the
      B3LYP functional with the 6-311+G* and 6-311+G** basis sets. Urea monomers have
      nonplanar minima at all the levels studied, even in the aqueous phase. In the
      case of glycinamide, the intramolecular hydrogen bond formed from the amide to
      the amine is important for stabilizing the global minimum. Bond rotations and
      nitrogen inversion barriers for glycinamide conformations have also been
      reported. The DFT calculated results suggest that urea conformers interact
      preferentially with the {111} surface of sodium chloride and such interactions
      can be responsible for the change in the habit of sodium chloride. Glycinamide
      conformers have a lower affinity toward the {111} surface of sodium chloride in
      water. The pyramidality of nitrogens in urea conformers does not influence the
      relative trends of interaction energies with sodium chloride surfaces. The mode
      of interactions predicted at the LDA/PWC/DND level for urea and glycinamide with
      sodium chloride for both slab and cluster models shows that the amide
      functionality (-CONH2) interacts with both Na(+) and Cl(-) ions on the {100}
      surface; however, the carbonyl oxygen of these additives predominantly interacts
      with the sodium ions on the {111} surface.

PMID- 17429986
TI  - Corrosion studies and interfacial bonding of urea/poly(dimethylsiloxane) sol/gel
      hydrophobic coatings on AA 2024 aluminum alloy.
AB  - Bis[(ureapropyl)triethoxysilane] bis(propyl)-terminated-polydimethylsiloxane 1000
      (PDMSU), an organic-inorganic hybrid, diluted in either EtOH or a mixture of EtOH
      PrOH, was used in thin film form (<200 nm) to inhibit the corrosion of AA 2024
      alloy. Potentiodynamic, time-dependent cyclovoltammetric measurements and salt
      spray tests showed that the corrosion inhibition of the latter was 10 times
      higher than that of the former films. This was correlated with the higher degree
      of hydrolysis and the formation of more open polyhedral silsesquioxane species
      (T2) in the bulk heat-treated PDMSU/EtOH-PrOH xerogels (29Si NMR spectra). The
      structure of the coatings deposited on AA 2024 Al alloy was deduced from the
      infrared reflection-absorption (IR RA) spectra, which revealed more extensive
      urea-urea interactions and more efficient silane-Al interface bonding for the
      PDMSU/EtOH-PrOH coatings with higher corrosion inhibition. Ex situ IR RA
      potentiodynamic spectroelectrochemical measurements of PDMSU coatings revealed
      that their degradation did not proceed via the formation of silanol groups and
      consequent hydration of the coatings but that they decomposed above E(corr) by
      forming fragments composed of -CH2- segments in an all-trans conformation.

PMID- 17429987
TI  - Gold nanoparticles protected with pH and temperature-sensitive diblock
      copolymers.
AB  - Aqueous dispersions of gold nanoparticles protected with a stimuli-sensitive
      diblock copolymer were studied as a function of pH and temperature.
      Poly(methacrylic acid)-block-poly(N-isopropylacrylamide), PMAA-b-PNIPAM,
      copolymer was synthesized using the RAFT technique. A one-pot method utilizing
      the dithiobenzoate functionalized polymer was used to prepare gold nanoparticles
      protected with PMAA-b-PNIPAM. The gold nanoparticles coated with block
      copolymers, with the PNIPAM block bound to the particle surface and PMAA as an
      outer block form stimuli-sensitive aggregates in water. The changes in the
      absorption maxima of the surface plasmon resonance, SPR, of the gold particles
      and in the size of the aggregates were investigated as a function of pH and
      temperature. pH was observed to affect the size of the aggregates, whereas the
      effect of temperature was moderate. However, a blue shift in the SPR was observed
      both with decreasing pH and increasing temperature. Whereas the PMAA blocks
      control the colloidal stability of the particles and their aggregates, the thermo
      sensitive PNIPAM blocks have a noticeable effect on the polarity of the immediate
      surroundings of the particles.

PMID- 17429988
TI  - Self-assembly of medium-chain alkyl monoglucosides in ammonium sulfate solutions
      with poly(ethylene glycol).
AB  - We study the phase behavior and microstructure of alkyl-beta-monoglucosides with
      intermediate chain lengths (octyl- and nonyl-beta-glucoside) in aqueous solutions
      containing ammonium sulfate and poly(ethylene glycol) (PEG). When the glucoside
      surfactants are mixed with PEG of molecular weight 3350 or larger, two different
      phase transitions are observed in the temperature range 0-100 degrees C, with
      lower and upper miscibility gaps separated by a one-phase isotropic region.
      Isothermal titration calorimetry is used to quantify the effect of PEG on the
      micellization properties of the alkyl monoglucosides, whereas small-angle neutron
      scattering gives insight into the microstructure of the surfactant/polymer
      mixtures near the liquid-liquid phase boundary. Results show that the range and
      the strength of the interactions in these solutions are highly affected by the
      presence of PEG. Solutions with nonyl-beta-glucoside contain larger micelles than
      those with octyl-beta-glucoside, and the intermicellar interactions are much
      stronger and longer ranged. The relevance of these findings for membrane protein
      crystallization is discussed.

PMID- 17429989
TI  - Understanding the dissolution of zeolites.
AB  - Scientific knowledge of how zeolites, a unique classification of microporous
      aluminosilicates, undergo dissolution in aqueous hydrochloric acid solutions is
      limited. Understanding the dissolution of zeolites is fundamental to a number of
      processes occurring in nature and throughout industry. To better understand the
      dissolution process, experiments were carried out establishing that the Si-to-Al
      ratio controls zeolite framework dissolution, by which the selective removal of
      aluminum constrains the removal of silicon. Stoichiometric dissolution is
      observed for Type 4A zeolite in HCl where the Si-to-Al ratio is equal to 1.0.
      Framework silicon dissolves completely during Type 4A dissolution and is followed
      by silicate precipitation. However, for the zeolite analcime which has a Si-to-Al
      ratio of 2.0 dissolves non-stoichiometrically as the selective removal of
      aluminum results in partially dissolved silicate particles followed by silicate
      precipitation. In Type Y zeolite, exhibiting a Si-to-Al ratio of 3.0, there is
      insufficient aluminum to weaken the structure and cause silicon to dissolve in
      HCl. Thus, little or no precipitation is observed, and amorphous undissolvable
      silicate particles remain intact. The initial dissolution rates of Type Y and 4A
      zeolites demonstrate that dissolution is constrained by the number of available
      reaction sites, and a selective removal rate parameter is applied to delineate
      the mechanism of particle dissolution by demonstrating the kinetic influence of
      the Si-to-Al ratio. Zeolite framework models are constructed and used to
      undergird the basic dissolution mechanism. The framework models, scanning
      electron micrographs of partially dissolved crystals, and experimentally measured
      dissolution rates all demonstrate that a zeolite's Si-to-Al framework ratio plays
      a universal role in the dissolution mechanism, independent of framework type.
      Consequently, the unique mechanism of zeolite dissolution has general
      implications on how petroleum reservoir stimulation treatments should be
      designed.

PMID- 17429990
TI  - Urinary proteome profiling using microfluidic technology on a chip.
AB  - Clinical diagnostics and biomarker discovery are the major focuses of current
      clinical proteomics. In the present study, we applied microfluidic technology on
      a chip for proteome profiling of human urine from 31 normal healthy individuals
      (15 males and 16 females), 6 patients with diabetic nephropathy (DN), and 4
      patients with IgA nephropathy (IgAN). Using only 4 microL of untreated urine,
      automated separation of proteins/peptides was achieved, and 1-7 (3.8 +/- 0.3)
      spectra/bands of urinary proteins/peptides were observed in the normal urine,
      whereas 8-16 (11.3 +/- 1.2) and 9-14 (10.8 +/- 1.2) spectra were observed in
      urine samples of DN and IgAN, respectively. Coefficient of variations of
      amplitudes of lower marker (1.2 kDa), system spectra (6-8 kDa), and upper marker
      (260.0 kDa) were 22.84, 24.92, and 32.65%, respectively. ANOVA with Tukey post
      hoc multiple comparisons revealed 9 spectra of which amplitudes significantly
      differed between normal and DN urine (DN/normal amplitude ratios ranged from 2.9
      to 3102.7). Moreover, the results also showed that 3 spectra (with molecular
      masses of 12-15, 27-28, and 34-35 kDa) were significantly different between DN
      and IgAN urine (DN/IgAN amplitude ratios ranged from 3.9 to 7.4). In addition to
      the spectral amplitudes, frequencies of some spectra could differentiate the
      normal from the diseased urine but could not distinguish between DN and IgAN.
      There was no significant difference, regarding the spectral amplitude or
      frequency, observed between males and females. These data indicate that the
      microfluidic chip technology is applicable for urinary proteome profiling with
      potential uses in clinical diagnostics and biomarker discovery.

PMID- 17429991
TI  - New methodological approach for the vanadium K-edge X-ray absorption near-edge
      structure interpretation: application to the speciation of vanadium in oxide
      phases from steel slag.
AB  - This paper presents a comparison between several methods dedicated to the
      interpretation of V K-edge X-ray absorption near-edge structure (XANES) features.
      V K-edge XANES spectra of several V-bearing standard compounds were measured in
      an effort to evaluate advantages and limits of each method. The standard
      compounds include natural minerals and synthetic compounds containing vanadium at
      various oxidation state (from +3 to +5) and in different symmetry (octahedral,
      tetrahedral, and square pyramidal). Correlations between normalized pre-edge peak
      area and its centroid position have been identified as the most reliable method
      for determining quantitative and accurate redox and symmetry information for
      vanadium. This methodology has been previously developed for the Fe K edge. It is
      also well adapted for the V K edge and is less influenced by the standard choice
      than other methods. This methodology was applied on an "environmental sample,"
      i.e., a well-crystallized leached steel slag containing vanadium as traces. Micro
      XANES measurements allowed elucidating the microdistribution of vanadium
      speciation in leached steel slag. The vanadium exhibits an important evolution
      from the unaltered to the altered phases. Its oxidation state increases from +3
      to +5 together with the decrease of its symmetry (from octahedral to
      tetrahedral).

PMID- 17429992
TI  - Hexagonal close packing of nonionic surfactant micelles in water.
AB  - The knowledge of the exact shapes of micelles in various micellar phases found in
      both lyotropic and thermotropic liquid crystals is very important to our
      understanding of the underlying principles of molecular self-assembly. In the
      current paper we present a detailed structural study of the hexagonal close
      packed (hcp, space group P63/mmc) micellar phase, observed in the binary mixtures
      of nonionic surfactant C12EO8 and water. The reconstructed electron density map
      of the phase shows perfectly spherical micelles. A spherical core/shell model of
      micelles, which fits the observed X-ray diffraction pattern satisfactorily, is
      subsequently constructed. The results confirm the previous assumption that the
      hcp phase consists of spherical close contacting micelles, each of which contains
      a low-density core of aliphatic parts and a high-density shell of hydrated
      ethylene oxide segments, with the gaps between the micelles filled by pure water.

PMID- 17429994
TI  - Low-energy electron attachment to 5'-thymidine monophosphate: modeling single
      strand breaks through dissociative electron attachment.
AB  - Mechanisms of low-energy electron (LEE) attachment and subsequent single-strand
      break (SSB) formation are investigated by density functional theory treatment of
      a simple model for DNA, i.e., the nucleotide, 5'-thymidine monophosphate (5'
      dTMPH). In the present study, the C5'-O5' bond dissociation due to LEE attachment
      has been followed along the adiabatic as well as on the vertical (electron
      attached to the optimized geometry of the neutral molecule) anionic surfaces
      using B3LYP functional and 6-31G* and 6-31++G** basis sets. Surprisingly, it is
      found that the PES of C5'-O5' bond dissociation in the anion radicals have
      approximately the same barrier for both adiabatic and vertical pathways. These
      results provide support for the hypothesis that transiently bound electrons
      (shape resonances) to the virtual molecular orbitals of the neutral molecule
      likely play a key role in the cleavage of the sugar-phosphate C5'-O5' bond in DNA
      resulting in the direct formation of single strand breaks without significant
      molecular relaxation. To take into account the solvation effects, we considered
      the neutral and anion radical of 5'-dTMP surrounded by 5 or 11 water molecules
      with Na+ as a counterion. These structures were optimized using the B3LYP/6-31G**
      level of theory. We find the barrier height for adiabatic C5'-O5' bond
      dissociation of 5'-dTMP anion radical in aqueous environment is so substantially
      higher than in the gas phase that the adiabatic route will not contribute to DNA
      strand cleavage in aqueous systems. This result is in agreement with experiment.

PMID- 17429995
TI  - Approximate values for force constant and wave number associated with a low
      frequency concerted motion in proteins can be evaluated by a comparison of X-ray
      structures.
AB  - Low-frequency internal motions in protein molecules play a key role in biological
      functions. A direct relationship between low-frequency motions and enzymatic
      activity has been suggested for bovine pancreatic ribonuclease (RNase A). The
      flexibility-function relationship in this enzyme has been attributed to a subtle
      and concerted breathing motion of the beta-sheet regions occurring upon substrate
      binding and release. Here, we calculate an approximate value for the force
      constant and the wave number of the low-frequency beta-sheet breathing motion of
      RNase A, by using the Boltzmann hypothesis on a set of data derived from a simple
      conventional structural superimposition of an unusual large number of X-ray
      structures available for the protein. The results agree with previous
      observations and with theoretical predictions on the basis of normal-mode
      analysis. To the best of our knowledge, this is the first example in which the
      wave number and the force constant of a low-frequency concerted motion in a
      protein are directly derived from X-ray structures.

PMID- 17429996
TI  - Tunable delocalization of unpaired electrons of nitroxide radicals for sickle
      cell disease drug improvements.
AB  - Hydroxyurea is a drug recently approved to treat sickle cell diseases.
      Hydroxyurea benefits the patients by increasing the level of fetal hemoglobin via
      a nitroxide radical pathway. Here, we report an unpaired-electron-delocalization
      approach to tune the stability of nitroxide radicals. In this approach, the
      substitution by an unsaturated alkyl group containing conjugated C=C double bonds
      for the hydrogen on the nitrogen atom attached to the hydroxyl of hydroxyurea can
      significantly increase its ability to generate nitroxide radical. Furthermore,
      the increase can be remarkably enhanced by increasing the number of conjugated
      C=C double bonds. For a hydroxyurea derivative that contains two conjugated C=C
      double bonds, the reaction rate to generate its radical is 118 times faster than
      that of hydroxyurea, and for a hydroxyurea derivative containing 20 conjugated
      C=C double bonds, the reaction rate to form its radical is 238 times faster than
      that of hydroxyurea. For this reason, hydroxyurea derivatives with conjugated C=C
      double bonds may constitute new potential drugs for the treatment of sickle-cell
      diseases.

PMID- 17429993
TI  - Proton solvation and transport in aqueous and biomolecular systems: insights from
      computer simulations.
AB  - The excess proton in aqueous media plays a pivotal role in many fundamental
      chemical (e.g., acid-base chemistry) and biological (e.g., bioenergetics and
      enzyme catalysis) processes. Understanding the hydrated proton is, therefore,
      crucial for chemistry, biology, and materials sciences. Although well studied for
      over 200 years, excess proton solvation and transport remains to this day
      mysterious, surprising, and perhaps even misunderstood. In this feature article,
      various efforts to address this problem through computer modeling and simulation
      will be described. Applications of computer simulations to a number of important
      and interesting systems will be presented, highlighting the roles of charge
      delocalization and Grotthuss shuttling, a phenomenon unique in many ways to the
      excess proton in water.

PMID- 17429997
TI  - Titanocene(II)-promoted stereoselective alkenylation utilizing (Z)-alkenyl
      sulfones.
AB  - The stereoselective alkenylation of unsaturated compounds by means of a (Z)
      alkenyl sulfone-titanocene(II) system is described. Treatment of alkynes and (Z)
      alkenyl methyl sulfones with the titanocene(II) reagent Cp2Ti[P(OEt)3]2 produced
      conjugated dienes. This alkenylation system is also applicable to polar C=O
      bonds; the simple mixing of carbonyl compounds, (Z)-alkenyl methyl sulfones, and
      the titanocene(II) reagent formed allylic alcohols. The advantages of
      alkenylation are that it requires no prepreparation of the alkenylmetal reagent
      and that it proceeds with complete stereoselectivity.

PMID- 17429999
TI  - Reaction of 2,3-allenoates with TsNBr2 in the presence of base: a facile highly
      stereoselective synthesis of (1E,2E)-3-bromo-4-oxo-N'-tosyl-2-alkenoxylimidic
      acid ethyl esters.
AB  - A novel reaction pathway of 2,3-allenoates with an electrophile (TsNBr2) in the
      presence of K2CO3 to produce (1E,2E)-3-bromo-4-oxo-N'-tosyl-2-alkenoxylimidic
      acid ethyl esters is reported. The reaction proceeds in a highly stereoselective
      fashion. A plausible mechanism to rationalize this reaction is also proposed.

PMID- 17429998
TI  - Reactions of nitroso hetero-Diels-Alder cycloadducts with azides: stereoselective
      formation of triazolines and aziridines.
AB  - The addition of azides to acylnitroso hetero-Diels-Alder cycloadducts derived
      from cyclopentadiene affords exo-triazolines in excellent yield. The reaction is
      greatly affected by the level of alkene strain, while sterically demanding azides
      do not hinder the reaction. Conversion of the triazolines to aziridines is also
      described.

PMID- 17430000
TI  - A fascination with 1,2-diacetals.
AB  - 1,2-Diacetals are readily prepared, rigid structural motifs that provide a wide
      range of opportunities for applications in natural product assembly. These uses
      encompass selective 1,2-diol or alpha-hydroxy acid protection, enantiotopic
      recognition and desymmetrization methods, chiral memory applications, and
      reactivity control in oligosaccharide synthesis, as well as functioning as
      templating components, chiral auxiliaries, and building blocks. 1,2-Diacetals are
      often more stable and lead to products with enhanced crystallinity compared to
      their five-ring acetonide counterparts. Many 1,2-diacetals have favorable NMR
      parameters, which facilitate structural assignment, particularly during
      asymmetric reaction processes.

PMID- 17430001
TI  - Advances in the chemistry of dipyrrins and their complexes.

PMID- 17430002
TI  - Synthesis of solution-phase phosphoramidite and phosphite ligand libraries and
      their in situ screening in the rhodium-catalyzed asymmetric addition of
      arylboronic acids.
AB  - Herein, we report the automated parallel synthesis of solution-phase libraries of
      phosphoramidite ligands for the development of enantioselective catalysts. The
      ligand libraries are screened in situ in the asymmetric rhodium-catalyzed
      addition of arylboronic acids to aldehydes and imines. It is shown that the
      described methodology results in the straightforward discovery of leads for
      highly efficient enantioselective catalysts.

PMID- 17430003
TI  - Magnetic properties of single-crystalline CoSi nanowires.
AB  - We have observed unusual ferromagnetic properties in single-crystalline CoSi
      nanowire ensemble, in marked contrast to the diamagnetic CoSi in bulk. High
      density freestanding CoSi nanowires with B20 crystal structure are synthesized by
      a vapor-transport-based method. The reaction of cobalt chloride precursor with a
      Si substrate produces high-aspect-ratio CoSi nanowires. The high-resolution
      transmission electron microscopy and electron diffraction studies reveal
      superlattice structure in CoSi nanowires with twice the lattice parameter of
      simple cubic CoSi lattice. The zero-field-cooled and field-cooled (ZFC-FC)
      measurements from the nanowire ensemble show freezing of the disordered surface
      spins at low temperatures. The magnetoresistance (MR) measurements of single
      nanowire devices show a negative MR whose magnitude gets larger at lower
      temperatures.

PMID- 17430004
TI  - Sensing characteristics of NIR localized surface plasmon resonances in gold
      nanorings for application as ultrasensitive biosensors.
AB  - The optical responses of 75-150 nm diameter gold nanorings to changes in local
      refractive index have been quantified by near-infrared extinction spectroscopy
      and compared to DDA calculations and an analytical approach. The "bulk"
      refractive index sensitivities of gold nanorings are substantially (>5 times)
      larger than those of nanodisks with similar diameters. Nanorings retain a
      significantly larger sensitivity than nanodisks at the same spectral position,
      demonstrating a clear shape dependence that may correlate to a systematic
      difference in the influence of the dielectric substrate. The nanoring bulk
      refractive index sensitivity scales linearly with plasmon peak position. The
      spectral sensitivity to thin films of alkanethiols gave a shift of approximately
      5.2 nm/CH2 unit while bulk sensitivities as high as 880 nm/RIU were observed, the
      highest such reported sensitivities. Both bulk and thin dielectric film
      sensitivities correlated well with theory. Real-time label-free monitoring of
      protein binding via molecular recognition was demonstrated.

PMID- 17430006
TI  - Vibronic coupling in semifluorinated alkanethiol junctions: implications for
      selection rules in inelastic electron tunneling spectroscopy.
AB  - Determining the selection rules for the interaction of tunneling charge carriers
      with molecular vibrational modes is important for a complete understanding of
      charge transport in molecular electronic junctions. Here, we report the low
      temperature charge transport characteristics for junctions formed from
      hexadecanethiol molecules having varying degrees of fluorination. Our results
      demonstrate that C-F vibrations are not observed in inelastic electron tunneling
      spectroscopy (IETS). Because C-F vibrations are almost purely dipole transitions,
      the insensitivity to fluorine substitution implies that Raman modes are preferred
      over infrared modes. Further, the lack of attenuation of the C-H vibrational
      modes with fluorine substitution suggests that either the scattering cross
      section is not an additive quantity or the physical position of a vibrational
      mode within the junction influences whether the transition is observed in IETS.

PMID- 17430007
TI  - Designing catalytic nanomotors by dynamic shadowing growth.
AB  - Using a geometric shadowing effect, a thin catalyst layer can be coated
      asymmetrically on the side of a nanorod backbone. Combining with substrate
      rotation, a dynamic shadowing growth technique has been developed to fabricate
      catalytic nanomotors such as rotary Si/Pt nanorods, rotary L-shaped Si/Pt and
      Si/Ag nanorods, and rolling Si/Ag nanosprings, and their autonomous motions have
      been demonstrated in a diluted H2O2 solution. This fabrication method reveals an
      optimistic step toward designing integrated nanomachines.

PMID- 17430005
TI  - Immuno gold nanocages with tailored optical properties for targeted photothermal
      destruction of cancer cells.
AB  - Gold nanocages with a relatively small size (e.g., approximately 45 nm in edge
      length) have been developed, and the structure of these nanocages was tailored to
      achieve strong absorption in the near-infrared (NIR) region for photothermal
      cancer treatment. Numerical calculations show that the nanocage has a large
      absorption cross section of 3.48 x 10(-14) m(2), facilitating conversion of NIR
      irradiation into heat. The gold nanocages were conjugated with monoclonal
      antibodies (anti-HER2) to target epidermal growth factor receptors (EGFR) that
      are overexpressed on the surface of breast cancer cells (SK-BR-3). Our
      preliminary photothermal results show that the nanocages strongly absorb light in
      the NIR region with an intensity threshold of 1.5 W/cm(2) to induce thermal
      destruction to the cancer cells. In the intensity range of 1.5-4.7 W/cm(2), the
      circular area of damaged cells increased linearly with the irradiation power
      density. These results suggest that this new class of bioconjugated gold
      nanostructures, immuno gold nanocages, can potentially serve as an effective
      photothermal therapeutic agent for cancer treatment.

PMID- 17430008
TI  - Long-range surface plasmons on ultrathin membranes.
AB  - A waveguide structure supporting long-range surface plasmon waves in any gaseous
      or liquid environment is described. The waveguide comprises a large area
      dielectric membrane of nanometric thickness upon which thin metal stripes and
      features are deposited. This structure allows the environment to surround the
      stripe thus ensuring that an essentially symmetric dielectric background is
      always present, as required to support the wave. The membrane perturbs the wave
      in a manner that significantly increases its surface sensitivity. The high
      surface sensitivity in concert with the ability to create long optical
      interaction length plasmonic structures leads to high sensitivity (bio)chemical
      sensors. Theoretical results describing the operation of the structure are given
      along with experimental results demonstrating the propagation of long-range
      surface plasmons in air and in liquid. The structure opens up a wealth of
      opportunities for research and application across many fields, including
      plasmonics, photonics, material science, surfaces, and solid-liquid interfaces.

PMID- 17430009
TI  - Electromigrated nanoscale gaps for surface-enhanced Raman spectroscopy.
AB  - Single-molecule detection with chemical specificity is a powerful and much
      desired tool for biology, chemistry, physics, and sensing technologies. Surface
      enhanced spectroscopies enable single-molecule studies, yet reliable substrates
      of adequate sensitivity are in short supply. We present a simple, scaleable
      substrate for surface-enhanced Raman spectroscopy (SERS) incorporating nanometer
      scale electromigrated gaps between extended electrodes. Molecules in the nanogap
      active regions exhibit hallmarks of very high Raman sensitivity, including
      blinking and spectral diffusion. Electrodynamic simulations show plasmonic
      focusing, giving electromagnetic enhancements approaching those needed for single
      molecule SERS.

PMID- 17430010
TI  - Hydrodynamic tensor density functional theory with correct susceptibility.
AB  - In a previous work the authors developed a family of orbital-free tensor
      equations for the density functional theory [J. Chem. Phys. 124, 024105 (2006)].
      The theory is a combination of the coupled hydrodynamic moment equation hierarchy
      with a cumulant truncation of the one-body electron density matrix. A basic
      ingredient in the theory is how to truncate the series of equation of motion for
      the moments. In the original work the authors assumed that the cumulants vanish
      above a certain order (N). Here the authors show how to modify this assumption to
      obtain the correct susceptibilities. This is done for N=3, a level above the
      previous study. At the desired truncation level a few relevant terms are added,
      which, with the right combination of coefficients, lead to excellent agreement
      with the Kohn-Sham Lindhard susceptibilities for an uninteracting system. The
      approach is also powerful away from linear response, as demonstrated in a
      nonperturbative study of a jellium with a repulsive core, where excellent
      matching with Kohn-Sham simulations is obtained, while the Thomas-Fermi and von
      Weiszacker methods show significant deviations. In addition, time-dependent
      linear response studies at the new N=3 level demonstrate the author's previous
      assertion that as the order of the theory is increased new additional transverse
      sound modes appear mimicking the random phase approximation transverse dispersion
      region.

PMID- 17430011
TI  - Electronic circular dichroism spectra from the complex polarization propagator.
AB  - The complex linear polarization propagator approach has been applied to the
      calculation of electronic circular dichroism spectra of 3R-chloro-1-butyne, 3R
      methylcyclopentanone, 3S-methylcyclohexanone, 4R-1,1-dimethyl-[3]
      (1,2)ferrocenophan-2-on, S-3,3,3',3'-tetramethyl-1,1'-spirobi[3H,2,1]
      benzoxaselenole, and the fullerene C84. Using time-dependent Kohn-Sham density
      functional theory, it is shown that a direct and efficient evaluation of the
      circular dichroism spectrum can be achieved. The approach allows for the
      determination of the circular dichroism at an arbitrary wavelength thereby, in a
      common formulation and implementation, covering the visible, ultraviolet, and x
      ray regions of the spectrum. In contrast to traditional methods, the entire
      manifold of excited states is taken into account in the calculation of the
      circular dichroism at a given wavelength.

PMID- 17430012
TI  - New method to analyze simulations of activated processes.
AB  - We present a new method to analyze molecular and Brownian dynamics simulations of
      activated processes based on the concept of mean first-passage times. The new
      method provides a simple and efficient strategy to evaluate reaction rates and it
      facilitates the localization of the transition state directly from the kinetics
      of the system without the need of thermodynamical considerations. It also
      provides a more rigorous value of the steady-state transition rate and gives
      valuable information about many important characteristics of the process. We
      illustrate the power of this new technique by its application to the study of
      nucleation in rare gases.

PMID- 17430013
TI  - Density matrix based time-dependent density functional theory and the solution of
      its linear response in real time domain.
AB  - A density matrix based time-dependent density functional theory is extended in
      the present work. Chebyshev expansion is introduced to propagate the linear
      response of the reduced single-electron density matrix upon the application of a
      time-domain delta-type external potential. The Chebyshev expansion method is more
      efficient and accurate than the previous fourth-order Runge-Kutta method and
      removes a numerical divergence problem. The discrete Fourier transformation and
      filter diagonalization of the first-order dipole moment are implemented to
      determine the excited state energies. It is found that the filter diagonalization
      leads to highly accurate values for the excited state energies. Finally, the
      density matrix based time-dependent density functional is generalized to
      calculate the energies of singlet-triplet excitations.

PMID- 17430014
TI  - Surface Green's function calculations: a nonrecursive scheme with an infinite
      number of principal layers.
AB  - A novel computational method for a surface Green's function matrix is introduced
      for the calculation of electrical current in molecular wires. The proposed
      nonrecursive approach includes an infinite number of principal layers and yields
      the second-order matrix equation for the transformed Green's function matrix. The
      solution is found by the direct diagonalization of the auxiliary matrix without
      any iteration process. As soon as complex roots of the auxiliary matrix
      (approximately GS) are calculated, the gaps and the bands in the surface
      electronic structure are found. It is shown that the solution of a second-order
      matrix equation determines the spectral density matrix, that is, the density of
      states for noninteracting electrons. Single and double principal layer models are
      studied both analytically and numerically. The energy interval for nonvanishing
      spectral matrices is determined. This method is applicable to matrices of any
      rank.

PMID- 17430015
TI  - Exact analytical evaluation of time dependent transmission coefficient from the
      method of reactive flux for an inverted parabolic barrier.
AB  - The paper demonstrates an elegant way of combining the normal mode analysis and
      the method of reactive flux to evaluate the time dependent transmission
      coefficient for a classical particle coupled to a set of harmonic oscillators,
      surmounting a one dimensional barrier. The author's analysis reproduces the
      results of Kohen and Tannor [J. Chem. Phys. 103, 6013 (1995)] and Bao [J. Chem.
      Phys. 124, 114103 (2006)]. Moreover the use of normal mode analysis has a better
      physical meaning.

PMID- 17430016
TI  - Path integral formulation for quantum nonadiabatic dynamics and the mixed quantum
      classical limit.
AB  - This work identifies geometric effects on dynamics due to nonadiabatic couplings
      in Born-Oppenheimer systems and provides a systematic method for deriving
      corrections to mixed quantum classical methods. Specifically, an exact path
      integral formulation of the quantum nonadiabatic dynamics of Born-Oppenheimer
      systems is described. Stationary phase approximations to the propagator for full
      quantum dynamics are derived. It is shown that quantum corrections to mixed
      quantum classical methods can be obtained through stationary phase approximations
      to the full quantum dynamics. A rigorous description of the quantum corrections
      due to electronic nonadiabatic coupling on the nuclear dynamics within the
      Ehrenfest framework is obtained. The fewest switches surface hopping method is
      shown to be obtained as a quasiclassical approximation to the dynamics, and
      natural semiclassical extensions to include classically forbidden nonadiabatic
      transitions are suggested.

PMID- 17430017
TI  - Accurate calculation of anharmonic vibrational frequencies of medium sized
      molecules using local coupled cluster methods.
AB  - Local coupled cluster methods were applied for the automated generation of
      accurate multidimensional potential energy surfaces for a set of test molecules
      ranging from six to nine atoms. Based on these surfaces anharmonic fundamental
      frequencies were computed using vibrational self-consistent field and
      configuration interaction methods. The computed vibrational frequencies are
      compared to those obtained from similar calculations using conventional coupled
      cluster methods and to experimental values. The results from local and
      conventional methods are found to be of similar accuracy and in close agreement
      with experimental values. In addition, an efficient parallelization of the fully
      automated surface generation code is presented.

PMID- 17430018
TI  - Event-driven Brownian dynamics for hard spheres.
AB  - Brownian dynamics algorithms integrate Langevin equations numerically and allow
      to probe long time scales in simulations. A common requirement for such
      algorithms is that interactions in the system should vary little during an
      integration time step; therefore, computational efficiency worsens as the
      interactions become steeper. In the extreme case of hard-body interactions,
      standard numerical integrators become ill defined. Several approximate schemes
      have been invented to handle such cases, but little emphasis has been placed on
      testing the correctness of the integration scheme. Starting from the two-body
      Smoluchowski equation, the authors discuss a general method for the overdamped
      Brownian dynamics of hard spheres, recently developed by one of the authors. They
      test the accuracy of the algorithm and demonstrate its convergence for a number
      of analytically tractable test cases.

PMID- 17430019
TI  - Theory of ultrafast heterogeneous electron transfer: contributions of direct
      charge transfer excitations to the absorbance.
AB  - Absorption spectra related to heterogeneous electron transfer are analyzed with
      the focus on direct charge transfer transition from the surface attached molecule
      into the semiconductor band states. The computations are based on a model of
      reduced dimensionality with a single intramolecular vibrational coordinate but a
      complete account for the continuum of conduction band states. The applicability
      of this model to perylene on TiO2 has been demonstrated in a series of earlier
      papers. Here, based on a time-dependent formulation, the absorbance is calculated
      with the inclusion of charge transfer excitations. A broad parameter set inspired
      by the perylene TiO2 systems is considered. In particular, the description
      generalizes the Fano effect to heterogeneous electron transfer reactions.
      Preliminary simulations of measured spectra are presented for perylene-catechol
      attached to TiO2.

PMID- 17430020
TI  - Computation of free energy profiles with parallel adaptive dynamics.
AB  - We propose a formulation of an adaptive computation of free energy differences,
      in the adaptive biasing force or nonequilibrium metadynamics spirit, using
      conditional distributions of samples of configurations which evolve in time. This
      allows us to present a truly unifying framework for these methods, and to prove
      convergence results for certain classes of algorithms. From a numerical
      viewpoint, a parallel implementation of these methods is very natural, the
      replicas interacting through the reconstructed free energy. We demonstrate how to
      improve this parallel implementation by resorting to some selection mechanism on
      the replicas. This is illustrated by computations on a model system of
      conformational changes.

PMID- 17430021
TI  - Higher-order equation-of-motion coupled-cluster methods for electron attachment.
AB  - High-order equation-of-motion coupled-cluster methods for electron attachment (EA
      EOM-CC) have been implemented with the aid of the symbolic algebra program TCE
      into parallel computer programs. Two types of size-extensive truncation have been
      applied to the electron-attachment and cluster excitation operators: (1) the
      electron-attachment operator truncated after the 2p-1h, 3p-2h, or 4p-3h level in
      combination with the cluster excitation operator after doubles, triples, or
      quadruples, respectively, defining EA-EOM-CCSD, EA-EOM-CCSDT, or EA-EOM-CCSDTQ;
      (2) the combination of up to the 3p-2h electron-attachment operator and up to the
      double cluster excitation operator [EA-EOM-CCSD(3p-2h)] or up to 4p-3h and
      triples [EA-EOM-CCSDT(4p-3h)]. These methods, capable of handling electron
      attachment to open-shell molecules, have been applied to the electron affinities
      of NH and C2, the excitation energies of CH, and the spectroscopic constants of
      all these molecules with the errors due to basis sets of finite sizes removed by
      extrapolation. The differences in the electron affinities or excitation energies
      between EA-EOM-CCSD and experiment are frequently in excess of 2 eV for these
      molecules, which have severe multideterminant wave functions. Including higher
      order operators, the EA-EOM-CC methods predict these quantities accurate to
      within 0.01 eV of experimental values. In particular, the 3p-2h electron
      attachment and triple cluster excitation operators are significant for achieving
      this accuracy.

PMID- 17430022
TI  - Dynamics of quantum dissipation systems interacting with fermion and boson grand
      canonical bath ensembles: hierarchical equations of motion approach.
AB  - A hierarchical equations of motion formalism for a quantum dissipation system in
      a grand canonical bath ensemble surrounding is constructed on the basis of the
      calculus-on-path-integral algorithm, together with the parametrization of
      arbitrary non-Markovian bath that satisfies fluctuation-dissipation theorem. The
      influence functionals for both the fermion or boson bath interaction are found to
      be of the same path integral expression as the canonical bath, assuming they all
      satisfy the Gaussian statistics. However, the equation of motion formalism is
      different due to the fluctuation-dissipation theories that are distinct and used
      explicitly. The implications of the present work to quantum transport through
      molecular wires and electron transfer in complex molecular systems are discussed.

PMID- 17430023
TI  - Critical appraisal of the fewest switches algorithm for surface hopping.
AB  - In this paper the authors address the problem of internal consistency in
      trajectory surface hopping methods, i.e., the requirement that the fraction of
      trajectories running on each electronic state equals the probabilities computed
      by the electronic time-dependent Schrodinger equation, after averaging over all
      trajectories. They derive a formula for the hopping probability in Tully's
      "fewest switches" spirit that would yield a rigorously consistent treatment. They
      show the relationship of Tully's widely used surface hopping algorithm with the
      "exact" prescription that cannot be applied when running each trajectory
      independently. They also bring out the connection of the consistency problem with
      the coherent propagation of the electronic wave function and the artifacts caused
      by coherent Rabi-type oscillations of the state probabilities in weak coupling
      regimes. A real molecule (azobenzene) and two ad hoc models serve as examples to
      illustrate the above theoretical arguments. Following a proposal by Truhlar's
      group [Zhu et al., J. Chem. Phys. 121, 7658 (2004) Zhu et al., J. Chem. Theory
      Comput. 1, 527 (2005)], they apply a decoherence correction to the state
      probabilities, in conjunction with Tully's algorithm, and they obtain
      satisfactory results in terms of internal consistency and of agreement with the
      outcomes of quantum wave packet calculations.

PMID- 17430024
TI  - Embedding procedure for ab initio correlation calculations in group II metals.
AB  - In order to apply ab initio wave-function-based correlation methods to metals, it
      is desirable to split the calculation into a mean-field part and a correlation
      part. Whereas the mean-field part (here Hartree-Fock) is performed in the
      extended periodic system, it is necessary to use for the correlation part local
      wave-function-based correlation methods in finite fragments of the solid. For
      these finite entities it is necessary to construct an embedding. The authors
      suggest an embedding scheme which has itself no metallic character but can mimic
      the metal in the internal region, where the atoms are correlated. With this
      embedding it is also possible to localize the metallic orbitals in the central
      part. The long-range nonadditive contributions of metallicity and correlation are
      treated with the method of increments. In this paper they present different ways
      to construct such an embedding and discuss the influence of the embedding on the
      correlation energy of the solid.

PMID- 17430025
TI  - Couplings between electronic transitions in a subsystem formulation of time
      dependent density functional theory.
AB  - A subsystem formulation of time-dependent density functional theory (TDDFT)
      within the frozen-density embedding (FDE) framework and its practical
      implementation are presented, based on the formal TDDFT generalization of the FDE
      approach by Casida and Wesolowski [Int. J. Quantum Chem. 96, 577 (2004)]. It is
      shown how couplings between electronic transitions on different subsystems can be
      seamlessly incorporated into the formalism to overcome some of the shortcomings
      of the approximate TDDFT-FDE approach in use so far, which was only applicable
      for local subsystem excitations. In contrast to that, the approach presented here
      allows to include couplings between excitations on different subsystems, which
      become very important in aggregates composed of several similar chromophores,
      e.g., in biological or biomimetic light-harvesting systems. A connection to
      Forster- and Dexter-type excitation energy coupling expressions is established. A
      hybrid approach is presented and tested, in which excitation energy couplings are
      selectively included between different chromophore fragments, but neglected for
      inactive parts of the environment. It is furthermore demonstrated that the
      coupled TDDFT-FDE approach can cure the inability of the uncoupled FDE approach
      to describe induced circular dichroism in dimeric chromophores, a feature known
      as a "couplet," which is also related to couplings between (nearly) degenerate
      electronic transitions.

PMID- 17430026
TI  - Theoretical study on intermolecular interactions between furan and dihalogen
      molecules XY(X,Y=F,Cl,Br).
AB  - Equilibrium geometries, interaction energies, atomic charge, and charge transfer
      for the intermolecular interactions between furan and dihalogen molecules XY(X;
      Y=F,Cl,Br) were studied at the MP2aug-cc-pVDZ level. Three types of geometry are
      observed in these interactions: the pi-type geometry (I), in which the XY lies
      above the furan ring and almost perpendicularly to the C4-C5 bond of furan; the
      sigma-type geometry (II), where the X atom is pointed toward the nonbonding
      electron pair (n pair) of oxygen atom in furan; and the chi-type geometry (III),
      describing a blueshift hydrogen bond formed between the hydrogen atom of furan
      and dihalogen molecules XY. The calculated interaction energies show that the pi
      type structures are more stable than the corresponding sigma-type and chi-type
      structures. To study the nature of the intermolecular interactions, an energy
      decomposition analysis was carried out and the results indicate that both the pi
      type and sigma-type interactions are dominantly inductive energy in nature, while
      dispersion energy governs the chi-type interactions.

PMID- 17430027
TI  - Internal state distribution of the CF fragment from the 193 nm photodissociation
      of CFCl and CFBr.
AB  - The dynamics of the 193 nm photodissociation of the CFCl and CFBr molecules have
      been investigated in a molecular beam experiment. The CFCl and CFBr parent
      molecules were generated by pyrolysis of CHFCl2 and CFBr3, respectively, and the
      CFCl and the CF photofragment were detected by laser fluorescence excitation. The
      193 nm attenuation cross section of CFCl was determined from the reduction of the
      CF photofragment signal as a function of the photolysis laser fluence. The
      internal state distribution was derived from the analysis of laser fluorescence
      excitation spectra in the A 2Sigma+-X 2Pi band system. A very low degree of
      rotational excitation, with essentially equal A' and A" Lambda-doublet
      populations, and no vibrational excitation were found in the CF photofragment.
      The energy available to the photofragments is hence predominantly released as
      translational energy. The CF internal state distribution is consistent with the
      dissociation of a linear intermediate state. Considerations of CFCl electronic
      states suggest that a bent Rydberg state is initially excited.

PMID- 17430028
TI  - Observation-assisted optimal control of quantum dynamics.
AB  - This paper explores the utility of instantaneous and continuous observations in
      the optimal control of quantum dynamics. Simulations of the processes are
      performed on several multilevel quantum systems with the goal of population
      transfer. Optimal control fields are shown to be capable of cooperating or
      fighting with observations to achieve a good yield, and the nature of the
      observations may be optimized to more effectively control the quantum dynamics.
      Quantum observations also can break dynamical symmetries to increase the
      controllability of a quantum system. The quantum Zeno and anti-Zeno effects
      induced by observations are the key operating principles in these processes. The
      results indicate that quantum observations can be effective tools in the control
      of quantum dynamics.

PMID- 17430029
TI  - A molecular beam optical Stark study of the [15.8] and [16.0] 2Pi1/2-X 4Sigma-
      (0,0) band systems of rhodium monoxide, RhO.
AB  - The SR11(0) and SR11(1) branch features of the [15.8] and [16.0]2Pi1/2-X 4Sigma-
      (0,0) subband systems of rhodium monoxide, RhO, have been studied at near the
      natural linewidth limit of resolution by optical Stark spectroscopy using laser
      induced fluorescence detection. The Stark shifts and splittings were analyzed to
      produce the magnitude of the permanent electric dipole moment, |mu|, of 3.81(2) D
      for the X 4Sigma3/2- (v=0) state. The results are compared to density functional
      theory calculations. Trends in observed values of |mu| across the 4d series of
      transition metal monoxides are interpreted in terms of simple single
      configuration molecular orbital correlation diagrams.

PMID- 17430030
TI  - Formaldehyde photodissociation: dependence on total angular momentum and
      rotational alignment of the CO product.
AB  - Quasiclassical trajectory calculations are reported to investigate the effects of
      rotational excitation of formaldehyde on the branching ratios of the
      fragmentation products, H2+CO and H+HCO. The results of tens of thousands of
      trajectories show that increased rotational excitation causes suppression of the
      radical channel and enhancement of the molecular channel. Decomposing the
      molecular channel into "direct" and "roaming" channels shows that increased
      rotation switches from suppressing to enhancing the roaming products across our
      chosen energy range. However, decomposition into these pathways is difficult
      because the difference between them does not appear to have a distinct boundary.
      A vector correlation investigation of the CO rotation shows different
      characteristics in the roaming versus direct channels and this difference is a
      potentially useful signature of the roaming mechanism, as first speculated by
      Kable and Houston in their experimental study of photodissociation of
      acetaldehyde [P. L. Houston and S. H. Kable, Proc. Nat. Acad. Sci. 103, 16079
      (2006)].

PMID- 17430031
TI  - Infrared photodissociation of a water molecule from a flexible molecule-H2O
      complex: rates and conformational product yields following XH stretch excitation.
AB  - Infrared-ultraviolet hole-burning and hole-filling spectroscopies have been used
      to study IR-induced dissociation of the tryptamine.H2O and tryptamine.D2O
      complexes. Upon complexation of a single water molecule, the seven conformational
      isomers of tryptamine collapse to a single structure that retains the same
      ethylamine side chain conformation present in the most highly populated conformer
      of tryptamine monomer. Infrared excitation of the tryptamine.H2O complex was
      carried out using a series of infrared absorptions spanning the range of 2470
      3715 cm-1. The authors have determined the conformational product yield over this
      range and the dissociation rate near threshold, where it is slow enough to be
      measured by our methods. The observed threshold for dissociation occurred at 2872
      cm-1 in tryptamine.H2O and at 2869 cm-1 in tryptamine.D2O, with no dissociation
      occurring on the time scale of the experiment (approximately 2 micros) at 2745 cm
      1. The dissociation time constants varied from approximately 200 ns for the 2869
      cm-1 band of tryptamine.D2O to approximately 25 ns for the 2872 cm-1 band of
      tryptamine.H2O. This large isotope dependence is associated with a zero-point
      energy effect that increases the binding energy of the deuterated complex by
      approximately 190 cm-1, thereby reducing the excess energy available at the same
      excitation energy. At all higher energies, the dissociation lifetime was shorter
      than the pulse duration of our lasers (8 ns). At all wavelengths, the observed
      products in the presence of collisions are dominated by conformers A and B of
      tryptamine monomer, with small contributions from the other minor conformers. In
      addition, right at threshold (2869 cm-1), tryptamine.D2O dissociates exclusively
      to conformer A in the absence of collisions with helium, while both A and B
      conformational products are observed in the presence of collisions with helium.
      Using resolution-of-identity approximation to second-order Moller-Plesset binding
      energies extrapolated to the complete basis set limit and harmonic vibrational
      frequencies and transition states calculated at the density functional limit
      B3LYP/6-31+G* level of theory, Rice-Ramsperger-Kassel-Marcus (RRKM) predictions
      for the dissociation, isomerization, and water shuttling rates as a function of
      energy are made. At threshold, the experimental dissociation rate is almost 10(3)
      faster than RRKM predictions. Reasons for this apparent non-RRKM behavior will be
      discussed.

PMID- 17430032
TI  - Time-dependent density functional theory Ehrenfest dynamics: collisions between
      atomic oxygen and graphite clusters.
AB  - An ab initio direct Ehrenfest dynamics method with time-dependent density
      functional theory is introduced and applied to collisions of 5 eV oxygen atoms
      and ions with graphite clusters. Collisions at three different sites are
      simulated. Kinetic energy transfer from the atomic oxygen to graphite local
      vibrations is observed and electron-nuclear coupling resulting in electronic
      excitation within the graphite surface as well as alteration of the atomic charge
      is first reported in this paper. The three oxygen species studied, O(3P), O-(2P),
      and O+(4S), deposit different amounts of energy to the surface, with the highest
      degree of damage to the pi conjugation of the cluster produced by the atomic
      oxygen cation. Memory of the initial charge state is not lost as the atom
      approaches, in contrast to the usual assumption.

PMID- 17430033
TI  - Spin-orbit relativistic calculations of the core excitation spectra of SO2.
AB  - The time dependent density functional theory approach within the two-component
      zero-order relativistic approximation has been applied to the calculation of the
      core excitation spectra of SO2 molecule. The results obtained reproduce correctly
      the high resolution experimental spectra and allow the assignment of the spectral
      features both of the valence and Rydberg regions in the S 1s and O 1s spectra.
      For the S 2p threshold a correct description of the spin-orbit coupling as well
      as of the molecular field splitting appears mandatory for a reliable description
      of the spectrum and a detailed attribution of the complex Rydberg manifold of
      core excited states.

PMID- 17430034
TI  - On the vibronic level structure in the NO3 radical. I. The ground electronic
      state.
AB  - The model Hamiltonian approach of Koppel et al. [Adv. Chem. Phys. 57, 59 (1984)]
      is used to analyze the electronic spectroscopy of the nitrate radical (NO3).
      Simulations of negative ion photodetachment of NO3-, the X 2A2'<--B 2E' dispersed
      fluorescence spectrum of NO3, and the B 2E'<--X 2A2' absorption spectrum are all
      in qualitative agreement with experiment, indicating that the model Hamiltonian
      contains most or all of the essential physics that govern the strongly coupled X
      2A2' and B 2E' electronic states of the radical. All 14 bands seen in the
      dispersed fluorescence spectrum below 2600 cm-1 are assigned based on the
      simulations, filling in a few gaps left by previous work, and 7 additional bands
      below 4000 cm-1 are tentatively assigned. The assignment is predicated on the
      assumption that the nu3 level of NO3 is near 1000 cm-1 rather than 1492 cm-1 as
      is presently believed. Support for this reassignment (which associates the 1492
      cm-1 band with the nu1+nu4 level) comes from both the model Hamiltonian spectrum
      and a Fourier-transform infrared feature at 2585 cm-1 that is consistent with the
      large and positive cross anharmonicity between nu1 and nu4 needed for the
      alternative 1492 cm-1 assignment. An apparent systematic deficiency exists in the
      treatment of the model Hamiltonian for levels involving nu4. A discussion of the
      correlation between energy levels in the rigid D3h and C2v limits is
      illustrative, and provides insight into just how hard it is to treat the
      degenerate bending coordinate (q4) of NO3 accurately.

PMID- 17430035
TI  - Dissociative double photoionization of N2 using synchrotron radiation: appearance
      energy of the N2+ dication.
AB  - Photoionization cross sections for the production of the doubly charged ion N2+
      from N2 have been measured by means of synchrotron radiation in the photon energy
      range from 50 to 110 eV. The appearance energy for N2+ has been determined as
      55.2+/-0.2 eV, i.e., about 1.3 eV higher than the spectroscopic dissociation
      limit leading to the charge asymmetric dissociation channel N2+(2P)+N(4S) at 53.9
      eV. The onset of a second threshold at 59.9+/-0.2 eV is detected and the energy
      dependence of photoion intensities near the threshold regions is interpreted in
      terms of the Wannier theory. The production of the N2+ dication is discussed in
      terms of direct and indirect mechanisms for dissociative charge asymmetric
      photoionization and by comparison with the potential energy curves of the
      intermediate N(2)2+ dication. Experimental evidences for the opening of the
      Coulomb explosion channel N2++N+ at high photon energies are provided by
      measuring the kinetic energy release spectra of N2+ fragments at selected photon
      energies.

PMID- 17430036
TI  - Infrared absorption of C6H5SO2 detected with time-resolved Fourier-transform
      spectroscopy.
AB  - C6H5SO2 radicals were produced upon irradiation of three flowing mixtures:
      C6H5SO2Cl in N2, C6H5Cl and SO2 in CO2, and C6H5Br and SO2 in CO2, with a KrF
      excimer laser at 248 nm. A step-scan Fourier-transform spectrometer coupled with
      a multipass absorption cell was employed to record the time-resolved infrared
      (IR) absorption spectra of reaction intermediates. Two transient bands with
      origins at 1087.7 and 1278.2 cm-1 are assigned to the SO2-symmetric and SO2
      antisymmetric stretching modes, respectively, of C6H5SO2. Calculations with
      density-functional theory (B3LYP/aug-cc-pVTZ and B3P86/aug-cc-pVTZ) predict the
      geometry and vibrational wave numbers of C6H5SO2 and C6H5OSO. The vibrational
      wave numbers and IR intensities of C6H5SO2 agree satisfactorily with the observed
      new features. Rotational contours of IR spectra of C6H5SO2 simulated based on
      predicted molecular parameters agree satisfactorily with experimental results for
      both bands. The SO2-symmetric stretching band is dominated by a- and c-type
      rotational structures and the SO2-antisymmetric stretching band is dominated by a
      b-type rotational structure. When C6H5SO2Cl was used as a precursor of C6H5SO2,
      C6H5SO2Cl was slowly reproduced at the expense of C6H5SO2, indicating that the
      reaction Cl+C6H5SO2 takes place. When C6H5Br/SO2/CO2 was used as a precursor of
      C6H5SO2, features at 1186 and 1396 cm-1 ascribable to C6H5SO2Br were observed at
      a later period due to secondary reaction of C6H5SO2 with Br. Corresponding
      kinetics based on temporal profiles of observed IR absorption are discussed.

PMID- 17430037
TI  - Spin-orbit vibronic coupling in 3Pi states of linear triatomic molecules.
AB  - The Renner-Teller vibronic-coupling problem of a 3Pi electronic state of a linear
      molecule is analyzed with the inclusion of the spin-orbit coupling of the 3Pi
      electronic state, employing the microscopic (Breit-Pauli) spin-orbit coupling
      operator for the two unpaired electrons. The 6x6 Hamiltonian matrix in a diabatic
      spin-electronic basis is obtained by an expansion of the molecular Hamiltonian in
      powers of the bending amplitude. The symmetry properties of the Hamiltonian with
      respect to the time-reversal operator and the relativistic vibronic angular
      momentum operator are analyzed. It is shown that there exists a linear vibronic
      coupling term of spin-orbit origin, which has not been considered so far in the
      Renner-Teller theory of 3Pi electronic states. While two of the six adiabatic
      electronic wave functions do not exhibit a geometric phase, the other four carry
      nontrivial topological phases which depend on the radius of the integration
      contour. The spectroscopic effects of the linear spin-orbit vibronic-coupling
      mechanism have been analyzed by numerical calculations of the vibronic spectrum
      for selected model examples.

PMID- 17430038
TI  - Infrared spectroscopy of pyrrole-2-carboxaldehyde and its dimer: a planar beta
      sheet peptide model?
AB  - Intermolecular interactions relevant for antiparallel beta-sheet formation
      between peptide strands are studied by Fourier transform infrared spectroscopy of
      the low temperature, vacuum-isolated model compound pyrrole-2-carboxaldehyde and
      its dimer in the N-H and C=O stretching range. Comparison to quantum chemical
      predictions shows that even for some triple-zeta quality basis sets, hybrid
      density functionals and Moller-Plesset perturbation calculations fail to provide
      a consistent and fully satisfactory description of hydrogen bond induced
      frequency shifts and intensity ratios in the double-harmonic approximation. The
      latter approach even shows problems in reproducing the planar structure of the
      dimer and the correct sign of the C=O stretching shift for standard basis sets.
      The effect of matrix isolation is modeled by condensing layers of Ar atoms on the
      isolated monomer and dimer. The dimer structure is discussed in the context of
      the peptide beta-sheet motif.

PMID- 17430039
TI  - Rate coefficients for reaction and for rotational energy transfer in collisions
      between CN in selected rotational levels (X 2Sigma+, v=2, N=0, 1, 6, 10, 15, and
      20) and C2H2.
AB  - Rate coefficients (ktot,Ni) are reported (a) for total removal
      (reactive+inelastic) of CN(X2Sigma+,v=2,Ni) radicals from selected rotational
      levels (Ni=0, 1, 6, 10, 15, and 20) and (b) for state-to-state rotational energy
      transfer (ki-->f) between levels Ni and other rotational levels Nf in collisions
      with C2H2. CN radicals were generated by pulsed laser photolysis of NCNO at 573
      nm. A fraction of the radicals was then promoted to a selected rotational level
      in v=2 using a tunable infrared "pump" laser operating at approximately 2.45
      microm, and the subsequent fate of this subset of radicals was monitored using
      pulsed laser-induced fluorescence (PLIF). Values of ktot,Ni were determined by
      observing the decay of the PLIF signals as the delay between pump and probe laser
      pulses was systematically varied. In a second series of experiments, double
      resonance spectra were recorded at a short delay between the pump and probe laser
      pulses. Analysis of these spectra yielded state-to-state rate coefficients for
      rotational energy transfer, ki-->f. The difference between the sum of these rate
      coefficients, Sigmafki-->f, and the value of ktot,Ni for the same level Ni is
      attributed to the occurrence of chemical reaction, yielding values of the
      rotationally selected rate coefficients (kreac,Ni) for reaction of CN from
      specified rotational levels. These rate coefficients decrease from (7.9+/
      2.2)x10(-10) cm3molecule-1 s-1 for Ni=0 to (0.8+/-1.3)x10(-10) cm3 molecule-1 s-1
      for Ni=20. The results are briefly discussed in the context of microcanonical
      transition state theory and the statistical adiabatic channel model.

PMID- 17430040
TI  - Ab initio ground and excited state potential energy surfaces for NO-Kr complex
      and dynamics of Kr solids with NO impurity.
AB  - The intermolecular potentials for the NO(X 2Pi)-Kr and NO(A 2Sigma+)-Kr systems
      have been calculated using highly accurate ab initio calculations. The spin
      restricted coupled cluster method for the ground 1 2A' state [NO(X 2Pi)-Kr] and
      the multireference singles and doubles configuration interaction method for the
      excited 2 2A' state [NO(A 2Sigma+)-Kr], respectively, were used. The potential
      energy surfaces (PESs) show two linear wells and one that is almost in the
      perpendicular position. An analytical representation of the PESs has been
      constructed for the triatomic systems and used to carry out molecular dynamics
      (MD) simulations of the NO-doped krypton matrix response after excitation of NO.
      MD results are shown comparatively for three sets of potentials: (1) anisotropic
      ab initio potentials [NO molecule direction fixed during the dynamics and
      considered as a point (its center of mass)], (2) isotropic ab initio potentials
      (isotropic part in a Legendre polynomial expansion of the PESs), and (3) fitted
      Kr-NO potentials to the spectroscopic data. An important finding of this work is
      that the anisotropic and isotropic ab initio potentials calculated for the Kr-NO
      triatomic system are not suitable for describing the dynamics of structural
      relaxation upon Rydberg excitation of a NO impurity in the crystal. However, the
      isotropic ab initio potential in the ground state almost overlaps the published
      experimental potential, being almost independent of the angle asymmetry. This
      fact is also manifested in the radial distribution function around NO. However,
      in the case of the excited state the isotropic ab initio potential differs from
      the fitted potentials, which indicates that the Kr-NO interaction in the matrix
      is quite different because of the presence of the surrounding Kr atoms acting on
      the NO molecule. MD simulations for isotropic potentials reasonably reproduce the
      experimental observables for the femtosecond response and the bubble size but do
      not match spectroscopic results. A general overall view of the results suggests
      that, when the Kr-NO interaction takes place inside the matrix, potentials are
      rather symmetric and less repulsive than those for the triatomic system.

PMID- 17430041
TI  - Zero-field nuclear magnetic resonance in high field by modulated rf sequences.
AB  - The authors propose a novel approach to design and evaluate sequences for zero
      field NMR spectra in high field (ZFHF) by using amplitude and phase modulated rf
      sequences. ZFHF provide sharp peaks for the dipolar interaction between two
      nuclear spins even if the orientation of the molecules is distributed. The
      internuclear distance r can be directly obtained from the peak position which is
      proportional to r-3. Numerous ZFHF sequences are obtained. A sequence is selected
      from them by the systematic evaluation of the sequences. The new ZFHF sequence is
      less affected by chemical shift anisotropy (CSA) than the previous sequences; the
      sequence can be used for systems with large CSA such as a dipolar coupled 13C
      pair system under realistically high field. 13C ZFHF spectra of 13C2 diammonium
      succinate and 13C2 diammonium oxalate were observed under the 9.4 T field.

PMID- 17430042
TI  - Influence of electric field on the hydrogen bond network of methanol.
AB  - The understanding of the structure of hydrogen (H) bonding liquids in electric
      (E) fields is important in the context of several areas of research, such as
      electrochemistry, surface science, and thermodynamics of electrolyte solutions.
      We had earlier presented a general thermodynamic framework for this purpose, and
      had shown that the application of E field enhances H-bond interactions among
      water molecules. The present investigation with methanol suggests a different
      result-the H-bond structure, as indicated by the average number of H bonds per
      molecule, goes through a maxima with increasing field strength. This result is
      explained based on the symmetry in the location of the H-bonding sites in the two
      types of molecules.

PMID- 17430043
TI  - Surface tension and scaling of critical nuclei in diatomic and triatomic fluids.
AB  - Density functional theory has been used to investigate surface tension and
      scaling of critical clusters in fluids consisting of diatomic and rigid triatomic
      molecules. The atomic sites are hard spheres with attractive interactions
      obtained from the tail part of the Lennard-Jones potential. Asymmetry in
      attractive interactions between the atomic sites has been introduced to cause
      molecular orientation and oscillatory density profiles at liquid-vapor
      interfaces. The radial dependence of cluster surface tension in fluids showing
      modest orientation in unimolecular layer at the interface or no orientation at
      all resembles the surface tension behavior of clusters in simple monoatomic
      fluids, although the surface tension maximum becomes more pronounced with
      increasing chain length of the molecule. Surface tension of clusters having
      multiple oscillatory layers at the interface shows a prominent maximum at small
      cluster sizes; however, the surface tension of large clusters is lower than the
      planar value. The scaling relation for the number of molecules in the critical
      cluster and the nucleation barrier height developed by McGraw and Laaksonen
      [Phys. Rev. Lett. 76, 2754 (1996)] are well obeyed for fluids with little
      structure at liquid-vapor interface. However, fluids having enhanced interfacial
      structure show some deviation from the particle number scaling, and the barrier
      height scaling breaks up seriously.

PMID- 17430044
TI  - Rotation of methyl radicals in a solid argon matrix.
AB  - Electron spin resonance (ESR) measurements were carried out to study the rotation
      of methyl radicals (CH3) in a solid argon matrix at 14-35 K temperatures. The
      radicals were produced by dissociating methane by plasma bursts generated either
      by a focused 193 nm laser radiation or a radio frequency discharge device during
      the gas condensation on the substrate. The ESR spectrum exhibits axial symmetry
      at the lowest temperature and is ascribed to ground state molecules with
      symmetric total nuclear spin function I=3/2. The hyperfine anisotropy (Aparallel)
      Aperpendicular) was found to be -0.01 mT, whereas that of the g value was 2.5x10(
      5). The anisotropy is observed for the first time in Ar and is manifested by the
      splitting of the low-field transition. Elevation of temperature leads reversibly
      to the appearance of excited state contribution having antisymmetric I=1/2. As a
      function of the sample temperature, the relative intensities of symmetric and
      antisymmetric spin states corresponding to ground and excited rotor states,
      respectively, proton hyperfine and electron g-tensor components, and spin-lattice
      relaxation rates were determined by a numerical fitting procedure. The
      experimental observations were interpreted in terms of a free rotation about the
      C3 axis and a thermal activation of the C2-type rotations above 15 K. The ground
      and excited rotational state energy levels were found to be separated by 11.2 cm
      1 and to exhibit significantly different spin-lattice coupling. A crystal field
      model has been applied to evaluate the energy levels of the hindered rotor in the
      matrix, and crystal field parameter varepsilon4=-200 cm-1, corresponding to a 60
      cm-1 effective potential barrier for rotation of the C3 axis, was obtained.

PMID- 17430045
TI  - X-ray scattering intensities of water at extreme pressure and temperature.
AB  - We have calculated the coherent x-ray scattering intensity of several phases of
      water under high pressure using the ab initio density functional theory (DFT).
      Our calculations span the molecular liquid, ice VII, and superionic solid phases,
      including the recently predicted symmetrically hydrogen bonded region. We compute
      simulated spectra for ice VII and superionic water. We provide new atomic
      scattering form factors for water at extreme conditions, which take into account
      frequently neglected changes in ionic charge and electron delocalization. We show
      that our modified atomic form factors allow for a nearly exact comparison with
      the total x-ray scattering intensities calculated from DFT. Finally, we analyze
      the effect of their new form factors have on the determination of the oxygen
      oxygen radial distribution function from experiment.

PMID- 17430046
TI  - Transition functions and correlation functions in the analysis of dynamic
      systems.
AB  - An understanding of the dynamic behavior of complex systems such as supercooled
      liquids requires a knowledge of the microscopic processes occurring in them.
      Correlation functions, which can be derived from experimental measurements of
      macroscopic properties or from computer simulations, cannot distinguish between
      particles that have never moved and those that have changed their position or
      state and then returned to the original one. Such a distinction can be obtained
      from the comparison of a correlation function with the transition function, i.e.,
      the fraction of particles that have never moved up to time t. As the author
      demonstrates by an extension of his recently published results for the
      ferromagnetic Potts model [J. Chem. Phys. 124, 214508 (2006)], valuable insights
      into the microscopic behavior of a system can be obtained from such a comparison.
      A generalization of the transition function to a first passage function can
      provide useful extra insights.

PMID- 17430047
TI  - Synthesis and spectroscopy of CdS nanoparticles in amphiphilic diblock copolymer
      micelles.
AB  - Amphiphilic diblock copolymers with the same hydrophilic but different
      hydrophobic blocks were used as stabilizing agents to prepare cadmium sulfide
      nanoparticles in aqueous solutions containing 5% of different nonaqueous
      solvents: methanol, THF, and acetone. Nearly spherical nanoparticles with a fair
      degree of monodispersity and quantum yields of 1.5%-2% were obtained. Optical
      absorption band edge of the CdS nanoparticles shows a >0.5 eV blueshift compared
      to that of bulk CdS, indicating a high degree of quantum confinement. The
      absorption spectra, while insensitive to the nature of the hydrophobic blocks,
      exhibited a clear dependence on the nature of the minor, nonaqueous solvents. The
      photoluminescence in all cases was broad and redshifted, indicating a
      predominance of surface trap-state emission. Time-resolved photoluminescence
      demonstrates that the trap states are populated within the first 500 fs, followed
      by decay with a broad range of time constants from 0.1 to >10 ns, low energy
      traps decaying at a slower rate than high-energy ones. Time-resolved
      photoluminescence anisotropy revealed that the nanoparticles experience a local
      microviscosity very similar to that of bulk water. The experimental observations
      suggest that nanoparticle formation takes place predominantly in the hydrophilic
      corona region of the micelles, around specific points with high local
      concentration of the Cd+2-coordinating basic amine groups of hydrophilic block
      and/or the minor, nonaqueous solvent component.

PMID- 17430048
TI  - Accurate measurement of longitudinal cross-relaxation rates in nuclear magnetic
      resonance.
AB  - The accuracy of the determination of longitudinal cross-relaxation rates in NMR
      can be improved by combining symmetrical reconversion with suitable operator
      swapping methods that lead to the averaging of differences in autorelaxation
      rates and eliminate the effects of cross relaxation with the environment. The
      principles are first discussed for an isolated two-spin system comprising a pair
      of 15N and 1HN nuclei subjected to chemical shift anisotropy and dipole-dipole
      relaxation, and then extended to include further protons. The gains in accuracy
      are demonstrated experimentally for the protein ubiquitin.

PMID- 17430049
TI  - Equation of state for expanded fluid mercury: variational theory with many-body
      interaction.
AB  - A variational associating fluid theory is proposed to describe equations of state
      for expanded fluid mercury. The theory is based on the soft-sphere variational
      theory, incorporating an ab initio diatomic potential and an attractive many-body
      potential; the latter is evaluated with quantum chemical methods and expressed as
      a function of the local atomic coordination number and the nearest-neighbor
      distance. The resultant equation of state can reproduce the observed gas-liquid
      coexistence curve with good accuracy, without introducing phenomenological
      effective pair potentials. Various thermodynamic quantities such as pressure,
      isocloric thermal pressure coefficient, adiabatic sound velocity, and specific
      heat are calculated over a wide density-temperature range and compared with
      available experimental data.

PMID- 17430050
TI  - Unique chemical reactivity of a graphene nanoribbon's zigzag edge.
AB  - The zigzag edge of a graphene nanoribbon possesses a unique electronic state that
      is near the Fermi level and localized at the edge carbon atoms. The authors
      investigate the chemical reactivity of these zigzag edge sites by examining their
      reaction energetics with common radicals from first principles. A "partial
      radical" concept for the edge carbon atoms is introduced to characterize their
      chemical reactivity, and the validity of this concept is verified by comparing
      the dissociation energies of edge-radical bonds with similar bonds in molecules.
      In addition, the uniqueness of the zigzag-edged graphene nanoribbon is further
      demonstrated by comparing it with other forms of sp2 carbons, including a
      graphene sheet, nanotubes, and an armchair-edged graphene nanoribbon.

PMID- 17430051
TI  - Molecular mechanism of transporting a polarizable iodide anion across the water
      CCl4 liquid/liquid interface.
AB  - The result of transferring a polarizable iodide anion across the H2O-CCl4
      liquid/liquid interface was investigated in this study. The computed transfer
      free energy profile or potential of mean force exhibits a minimum near the Gibbs
      dividing surface. These system characteristics are similar to those found in a
      corresponding study of iodide transfer across the H2O-vapor interface; however,
      the free energy minimum was lower at the H2O-vapor interface. Molecular dynamics
      simulations were also carried out to compare the concentrations of NaCl, NaBr,
      and NaI at the H2O-vapor and H2O-CCl4 interfaces. While the concentration of
      bromide and iodide ions were lower at the H2O-CCl4 interface when compared to the
      H2O-vapor interface, the chloride ion concentrations were similar at both
      interfaces. Analysis of the solvation structures of iodide and chloride ions
      revealed that the more polarizable iodide ion was less solvated than the chloride
      ion at the interface. This characteristic brought the iodide ion into greater
      contact with CCl4, resulting in repulsive interactions with CCl4 and reducing its
      tendency to move to the interface.

PMID- 17430052
TI  - Scenarios of heterogeneous nucleation and growth studied by cell dynamics
      simulation.
AB  - The dynamics of phase transformation due to homogeneous nucleation has long been
      analyzed using the classic Kolmogorov-Johnson-Mehl-Avrami (KJMA) theory. However,
      the dynamics of phase transformation due to heterogeneous nucleation has not been
      studied systematically even though it is vitally important technologically. In
      this report, the author studies the dynamics of heterogeneous nucleation
      theoretically and systematically using the phenomenological time-dependent
      Ginzburg-Landau (TDGL)-type model combined with the cell dynamics method. In this
      study the author focuses on the dynamics of phase transformation when the
      material is sandwiched by two supporting substrates. This model is supposed to
      simulate phase change storage media. Since both homogeneous and heterogeneous
      nucleations can occur simultaneously, the author predicts a few scenarios of
      phase transformation including homogeneous nucleation regime, heterogeneous
      nucleation regime, and the homogeneous-heterogeneous coexistence regime. These
      predictions are directly confirmed by numerical simulation using the TDGL model.
      The outcome of the study was that the KJMA formula has limited use when
      heterogeneous nucleation exists, but it could still give some information about
      the microscopic mechanism of phase transformation at various stages during phase
      transformation.

PMID- 17430053
TI  - Hot precursor reactions during the collisions of gas-phase oxygen atoms with
      deuterium chemisorbed on Pt(100).
AB  - We utilized direct rate measurements and temperature programmed desorption to
      investigate reactions that occur during the collisions of gaseous oxygen atoms
      with deuterium-covered Pt(100). We find that both D2O and D2 desorb promptly when
      an oxygen atom beam impinges upon D-covered Pt(100) held at surface temperatures
      ranging from 90 to 150 K, and estimate effective cross sections of 12 and 1.8 A2,
      respectively, for the production of gaseous D2O and D2 at 90 K. The yields of D2O
      and D2 that desorb at 90 K are about 13% and 2%, respectively, of the initial D
      atom coverage, though most of the D2O product molecules (approximately 80%)
      thermalize to the surface rather than desorb at the surface temperatures studied.
      Increasing the surface temperature from 90 to 150 K causes the D2O desorption
      rate to decay more quickly during O atom exposures to the surface and results in
      lower yields of gaseous D2O. We attribute the production of D2O and D2 in these
      experiments to reactions involving intermediates that are not thermally
      accommodated to the surface, so-called hot precursors. The results are consistent
      with the production of hot D2O involving first the generation of hot OD groups
      from the reaction O*+D(a)-->OD*, where the asterisk denotes a hot precursor,
      followed by the parallel pathways OD*+D(a)-->D2O* and OD*+OD(a)-->D2O*+O(a). The
      final reaction contributes significantly to hot D2O production only later in the
      reaction period when thermalized OD groups have accumulated on the surface, and
      it becomes less important at higher temperature due to depletion of the OD(a)
      concentration by thermally activated D2O production.

PMID- 17430054
TI  - Structures and stabilities of small lead oxide clusters PbmOn (m=1-4,n=1-2m).
AB  - The structures and stabilities of small lead oxide clusters PbmOn with m=1-4, n=1
      2m are systematically studied using density functional theory. It is found that
      the lowest-energy structures of all these clusters can be obtained by the
      sequential oxidation of small "core" lead clusters. For Pb-rich clusters (oxygen
      to-lead ratio<1), oxygen atoms favor bridge sites for Pb2On and Pb3On and surface
      sites for Pb4On. The lead-monoxide-like clusters (PbO)i (i=1-4) have great
      stability because of their significant dissociation energies and highest occupied
      molecular orbital-lowest unoccupied molecular orbital gaps. This suggests that
      they could be adopted as the building blocks of cluster-assembled materials. For
      O-rich clusters (oxygen-to-lead ratio>1), the grouping of oxygen atoms usually
      appears. It is found that the structures with a grouping of more than two oxygen
      atoms are unstable.

PMID- 17430055
TI  - Diffusion in a tube of varying cross section: numerical study of reduction to
      effective one-dimensional description.
AB  - Brownian dynamics simulations of the particle diffusing in a long conical tube
      (the length of the tube is much greater than its smallest radius) are used to
      study reduction of the three-dimensional diffusion in tubes of varying cross
      section to an effective one-dimensional description. The authors find that the
      one-dimensional description in the form of the Fick-Jacobs equation with a
      position-dependent diffusion coefficient, D(x), suggested by Zwanzig [J. Phys.
      Chem. 96, 3926 (1992)], with D(x) given by the Reguera-Rubi formula [Phys. Rev. E
      64, 061106 (2001)], D(x)=D/sq rt1+R'(x)2, where D is the particle diffusion
      coefficient in the absence of constraints, and R(x) is the tube radius at x, is
      valid when |R'(x)|<or=1. When |R'(x)|>1, higher spatial derivatives of the one
      dimensional concentration in the effective diffusion equation cannot be neglected
      anymore as was indicated by Kalinay and Percus [J. Chem. Phys. 122, 204701
      (2005)]. Thus the reduction to the effective one-dimensional description is a
      useful tool only when |R'(x)|<or=1 since in this case one can apply the powerful
      standard methods to analyze the resulting diffusion equation.

PMID- 17430056
TI  - Theory of electron localization at dielectric-metal interfaces: a continuum
      model.
AB  - Localization of electrons at dielectric-metal interfaces is studied in the
      framework of a continuum model. The layer of thickness L, with a negative
      electron affinity, is characterized by the static dielectric constant epsilons
      and by the optical dielectric constant epsiloninfinity. It is found that the
      electron localization along the plane of the interface occurs if the layer
      thickness exceeds a critical value Lc. In the case of a high polar layer, the
      electron energy of the localized ground state shows a nonmonotonic dependence on
      the layer thickness. A strong correlation between low-lying excitations and the
      spread of the localized state has been established. The magnitude of the
      correlation parameter is close to the analogous correlation for the solvated
      electron in the bulk. The localization dynamics is discussed in terms of
      relaxation along a polarization coordinate, which is directly connected to the
      polarization energy of the layer.

PMID- 17430057
TI  - Monte Carlo simulation of n-alkane adsorption isotherms in carbon slit pores.
AB  - The single component adsorption of alkanes in carbon slit pores was studied using
      configurational-biased grand canonical Monte Carlo simulations. Wide ranges of
      temperature, pressure, alkane chain length, and slit height were studied to
      evaluate their effects on adsorption. Adsorption isotherms and density and
      orientation profiles were calculated. The behavior of long alkanes at high
      temperatures was found to be similar to short alkanes at lower temperatures. This
      suggests that the isotherms may be related through the Polanyi potential theory.

PMID- 17430058
TI  - Role of charge transfer configurations in LaMnO3, CaMnO3, and CaFeO3.
AB  - A simple scheme is proposed to analyze the N-electron wave function obtained in
      embedded cluster calculations in valence bond terms such as ligand-to-metal
      charge transfer and non-charge-transfer determinants. The analysis is based on a
      unitary transformation of pairs of natural orbitals to optimal atomiclike
      orbitals. The procedure is applied to compare the degree of ionicity in NiO and
      MnO and to explain the existence or absence of Jahn-Teller distortions in LaMnO3,
      CaMnO3, and CaFeO3. The authors find that the ground state of LaMnO3 is dominated
      by non-charge-transfer configurations, whereas the charge transfer configurations
      dominate the ground state wave function in the other two perovskites.

PMID- 17430059
TI  - Fundamental measure theory in cylindrical geometry.
AB  - Density functional theory as proposed by Rosenfeld [Phys. Rev. Lett. 63, 980
      (1989)] is used to study hard sphere mixture exposed by cylindrically symmetric
      external field. Exploiting the symmetry of the system, explicit formulas for the
      weighted densities are derived. The resulting density profiles are compared with
      new grand canonical Monte Carlo simulations. The comparison reveals very good
      agreement between the predicted and simulated results even at high densities and
      very narrow pores. Finally, simple algorithms for computing complete elliptic
      functions of the first and second kinds that occur in the derived formulae are
      presented to make the paper self-contained.

PMID- 17430060
TI  - Observation of a transition in the water-nanoparticle formation process at 167 K.
AB  - Rapid-scan Fourier transform infrared spectroscopy of the vapor/solid formation
      process of water nanoparticles in the 180-140 K temperature range at thermal
      equilibrium conditions is reported. At 167 K a transition in the formation
      process was observed: the particle volume quintuples and the particle formation
      time triples within a temperature interval of +/-0.4 K caused by the temperature
      control. The authors interpret this behavior by an abrupt change in the
      nucleation rate of the H2O monomers in He buffer gas kept at 167 K and 200 mbar.
      A size and shape analysis of the particles during the formation process was
      carried out by application of the discrete dipole approximation method which
      delivers excellent accordance between experimental and calculated mid-IR spectra.
      Compared to other compact shapes (cube, prolate ellipsoid, and hexagonal prism)
      the ideal spherical shape fits the experimental spectra best. A distinct change
      in shape by particle conversion or agglomeration could be excluded to be involved
      in the formation process. As a possible explanation of the observed phenomenon, a
      transition from vapor/liquid/solid to vapor/solid nucleation with decreasing
      temperature is considered which was recently theoretically predicted by van
      Dongen and co-workers [J. Chem. Phys. 117, 5647 (2002); private communication; J.
      Chem. Phys. 120, 6314 (2004)].

PMID- 17430061
TI  - Kinetics of chain collapse in dilute polymer solutions: molecular weight and
      solvent dependences.
AB  - The molecular weight and solvent dependences of the characteristic time of chain
      collapse were studied for poly(methyl methacrylate) (PMMA) of the molecular
      weight Mw=6.4x10(6) and 1.14x10(7) in pure acetonitrile (AcN) and in the mixed
      solvent of AcN+water (10 vol %). The size of PMMA chains was measured as a
      function of the time after the quench by static light scattering and the chain
      collapse processes were expressed by the plot of the expansion factor alpha2 vs
      ln t. The chain collapse in the mixed solvent AcN+water (10 vol %) was found to
      occur much faster than that in pure AcN, though the measurement of the former
      collapse process required several hours. In order to make a comparison between
      the rates of chain collapses, the fast chain collapse process was superposed on
      the slow one by scaling the time of the fast process as gammat. The scale factor
      gamma was determined by comparing the chain collapse processes of nearly the same
      equilibrium expansion factor with each other. Accordingly, the superposition of
      the collapse for Mw=6.4x10(6) on that for Mw=1.14x10(7) yielded gammam=4.0+/-0.6
      for the process in AcN+water and 5.5+/-0.6 in AcN. The superposition of the chain
      collapse process in AcN+water on that in AcN yielded gammas=9.5+/-1.4 for
      Mw=6.4x10(6) and 12.0+/-1.8 for Mw=1.14x10(7). This analysis suggests that gammam
      and gammas are constant independent of each other. Thus, by assuming the
      molecular weight dependence of gammam approximately Mz, the characteristic time
      tauexp of chain collapse was conjectured as tauexp approximately kappaMz, where
      kappa reflects the nature of solvent species. The ratio of kappa for PMMA in AcN
      to that in AcN+water is given by gammas. The exponent was estimated to be z=2.4+/
      0.7 for AcN+water and 3.0+/-0.7 for AcN. These values are compatible with the
      theoretical prediction z=3 based on a phenomenological model, though the observed
      characteristic times are longer by several orders of magnitude than those of the
      theoretical prediction.

PMID- 17430062
TI  - A macromolecule in a solvent: adaptive resolution molecular dynamics simulation.
AB  - The authors report adaptive resolution molecular dynamics simulations of a
      flexible linear polymer in solution. The solvent, i.e., a liquid of tetrahedral
      molecules, is represented within a certain radius from the polymer's center of
      mass with a high level of detail, while a lower coarse-grained resolution is used
      for the more distant solvent. The high resolution sphere moves with the polymer
      and freely exchanges molecules with the low resolution region through a
      transition regime. The solvent molecules change their resolution and number of
      degrees of freedom on the fly. The authors show that their approach correctly
      reproduces the static and dynamic properties of the polymer chain and surrounding
      solvent.

PMID- 17430063
TI  - Density functional theory for copolymers confined in a nanoslit.
AB  - A density functional theory is developed for copolymers confined in a nanoslit on
      the basis of our previous work for homopolymers. The theory accurately captures
      the structural characteristics for diblock and alternating copolymers composed of
      hard-sphere or square-well segments. Satisfactory agreement is obtained between
      the theoretical predictions and simulation results in segment density profiles,
      segment fractions, and partition coefficients. Structures under confinement
      strongly depend on the substituent segment sizes for the hard-sphere copolymers
      and also on the segment-wall attractions for the square-well copolymers.
      Alternating copolymers are found to behave as homopolymers with effective segment
      size, and effective segment-segment and segment-wall interactions.

PMID- 17430064
TI  - Diffusive diffraction phenomenon in a porous polymer material observed by NMR
      using radio-frequency field gradients.
AB  - Pulsed field gradient NMR diffusion experiments can, in principle, lead to the
      "diffusive diffraction" phenomenon. In practice, its observation by gradients of
      the static magnetic field is difficult in real systems because they involve
      internal gradients due to the static magnetic field (necessary for polarizing
      nuclear spins). This latter drawback can be circumvented by using gradients of
      the radio-frequency (rf) field (the other magnetic field used in any NMR
      experiment). For the first time, by means of rf gradients, a so-called diffusive
      diffraction peak has been observed in a real porous system and its position
      provides a value of the mean distance between pores; this can be further
      complemented by the mean pore size determined from the dependence of the apparent
      diffusion coefficient with respect to the diffusion interval.

PMID- 17430065
TI  - Exciton transfer integrals between polymer chains.
AB  - The line-dipole approximation for the evaluation of the exciton transfer integral
      J between conjugated polymer chains is rigorously justified. Using this
      approximation, as well as the plane-wave approximation for the exciton center-of
      mass wave function, it is shown analytically that J approximately L when the
      chain lengths are smaller than the separation between them, or J approximately L
      1 when the chain lengths are larger than their separation, where L is the chain
      length. Scaling relations are also obtained numerically for the more realistic
      standing wave approximation for the exciton center-of-mass wave function, where
      it is found that for chain lengths larger than their separation J approximately L
      1.8 or J approximately L-2, for parallel or collinear chains, respectively. These
      results have important implications for the photophysics of conjugated polymers
      and self-assembled molecular systems, as the Davydov splitting in aggregates and
      the Forster transfer rate for exciton migration decrease with chain lengths
      larger than their separation. This latter result has obvious deleterious
      consequences for the performance of polymer photovoltaic devices.

PMID- 17430066
TI  - Simulation and theory of flexible equilibrium polymers under poor solvent
      conditions.
AB  - Grand canonical Monte Carlo simulation and simple statistical thermodynamic
      theory are used to model the aggregation and phase separation of systems of
      reversibly polymerizing monomers, capable of forming chains with or without the
      ability to cyclize into rings, with isotropic square-well attractions between
      nonbonded pairs of monomers. The general trend observed in simulation of chain
      only systems, as predicted in a number of published theoretical works, is that
      the critical temperature for phase separation increases and the critical monomer
      density decreases with rising polymer bond strength. Introduction of the
      equilibrium between chains and rings into the theory lowers the predicted
      critical temperature and increases the predicted critical density. While the
      chain-only theories predict a vanishing critical density in the limit of complete
      polymerization, when ring formation is taken into account the predicted critical
      density in the same limit approaches the density of the onset of the ring-chain
      transition. The theoretically predicted effect of cyclization on chemical
      potential is in good qualitative agreement with a subset of simulation results in
      which chain-only systems were compared with equilibrium mixtures of rings and
      chains. The influence of attractions on the aggregation number and radius of
      gyration of chains and rings observed in simulations is also discussed.

PMID- 17430067
TI  - Master equation approach to folding kinetics of lattice polymers based on
      conformation networks.
AB  - Based on the master equation with the inherent structure of conformation network,
      the authors investigate some important issues in the folding kinetics of lattice
      polymers. First, the topologies of conformation networks are discussed. Moreover,
      a new scheme of implementing Metropolis algorithm, which fulfills the condition
      of detailed balance, is proposed. Then, upon incorporating this new scheme into
      the geometric structure of conformation network the authors provide a theorem
      which can be used to place an upper bound on relaxation time. To effectively
      identify the kinetic traps of folding, the authors also introduce a new quantity,
      which is employed from the continuous time Monte Carlo method, called rigidity
      factor. Throughout the discussions, the authors analyze the results for different
      move sets to demonstrate the methods and to study the features of the kinetics of
      folding.

PMID- 17430068
TI  - Pair diffusion in quasi-one- and quasi-two-dimensional binary colloid
      suspensions.
AB  - The authors report the results of measurements of the center of mass and relative
      pair diffusion coefficients in quasi-one-dimensional (q1D) and quasi-two
      dimensional (q2D) binary colloid suspensions. The new results extend the findings
      of similar studies of one-component quasi-one-dimensional and quasi-two
      dimensional colloid suspensions. Our principal new finding is that the presence
      of the smaller diameter component can destroy the oscillatory structure of the
      separation dependence of the q2D relative pair diffusion coefficient of the large
      particles even though the oscillatory character of the large particle equilibrium
      pair correlation function remains prominent, and that no such effect occurs with
      the q1D suspension. An interpretation of these results is proposed.

PMID- 17430069
TI  - Statistical temperature molecular dynamics: application to coarse-grained beta
      barrel-forming protein models.
AB  - Recently the authors proposed a novel sampling algorithm, "statistical
      temperature molecular dynamics" (STMD) [J. Kim et al., Phys. Rev. Lett. 97,
      050601 (2006)], which combines ingredients of multicanonical molecular dynamics
      and Wang-Landau sampling. Exploiting the relation between the statistical
      temperature and the density of states, STMD generates a flat energy distribution
      and efficient sampling with a dynamic update of the statistical temperature,
      transforming an initial constant estimate to the true statistical temperature
      T(U), with U being the potential energy. Here, the performance of STMD is
      examined in the Lennard-Jones fluid with diverse simulation conditions, and in
      the coarse-grained, off-lattice BLN 46-mer and 69-mer protein models, exhibiting
      rugged potential energy landscapes with a high degree of frustration. STMD
      simulations combined with inherent structure (IS) analysis allow an accurate
      determination of protein thermodynamics down to very low temperatures, overcoming
      quasiergodicity, and illuminate the transitions occurring in folding in terms of
      the energy landscape. It is found that a thermodynamic signature of folding is
      significantly suppressed by accurate sampling, due to an incoherent contribution
      from low-lying non-native IS in multifunneled landscapes. It is also shown that
      preferred accessibility to such IS during the collapse transition is intimately
      related to misfolding or poor foldability.

PMID- 17430071
TI  - Matrix formulation of the surface-enhanced Raman optical activity theory.

PMID- 17430072
TI  - Comment on "nested stochastic simulation algorithm for chemical kinetic systems
      with disparate rates" [J. Chem. Phys. 123, 194107 (2005)].

PMID- 17430070
TI  - Preferential interaction between DNA and small ions in mixed-size counterion
      systems: Monte Carlo simulation and density functional study.
AB  - Competitive binding between counterions around DNA molecule is characterized
      using the preferential interaction coefficient of individual ion in single and
      mixed electrolyte solutions. The canonical Monte Carlo (MC) simulation, nonlinear
      Poisson-Boltzmann (PB) equation, and density functional theory (DFT) proposed in
      our previous work [Wang, Yu, Gao, and Luo, J. Chem. Phys. 123, 234904 (2005)] are
      utilized to calculate the preferential interaction coefficients. The MC
      simulations and theoretical results show that for single electrolyte around DNA,
      the preferential interaction coefficient of electrolyte decreases as the cation
      size is increased, indicating that the larger cation has less accumulation
      ability in the vicinity of DNA. For the mixed electrolyte solution, it is found
      that cation diameter has a significant effect on the competitive ability while
      anion diameter has a negligible effect. It proves that the preferential
      interaction coefficients of all ions decrease as the total ionic concentration is
      increased. The DFT generally has better performance than the PB equation does
      when compared to the MC simulation data. The DFT behaves quite well for the real
      ionic solutions such as the KCl-NaCl-H2O, NaCl-CaCl2-H2O, and CaCl2-MgCl2-H2O
      systems.

PMID- 17430074
TI  - Efficacy of murine monoclonal antibodies in RBC phenotyping of DAT-positive
      samples.
AB  - Determining the phenotype of patient RBCs that are positive by the DAT may prove
      problematic. Antigen typing of RBCs coated with IgG requires direct agglutinating
      reagents or chemical treatment (such as chloroquine diphosphate [CDP] or citric
      acid) to remove sufficient IgG to permit testing with IAT-reactive reagents. The
      citric acid elution method is commonly used in the United States; however,
      antigens in the Kell system are altered to the extent that they may appear to be
      absent by this method. There are a limited number of direct agglutinating
      monoclonal antibodies available. Murine monoclonal antibodies provide an
      additional tool for typing RBCs with a positive DAT. Five murine monoclonal IgG
      antibodies (anti-K: MIMA-22, MIMA-23; anti-Kpa: MIMA-21, MIMA-27; anti-Fya: MIMA
      19) were used in this study. Donor RBCs with known phenotypes were sensitized in
      vitro with alloanti-D, alloanti-c, and alloanti-K and with 20 autoantibodies
      (autoanti-D [n=3], autoanti-e [n=5], autoanti-Ce/e [n=5], autoanti-e+D+E [n=1],
      autoanti-I [n=1], and nonspecific [n=5]) to simulate a positive in vivo DAT. The
      sensitized RBCs were treated with CDP to remove IgG. To determine the efficacy of
      the murine monoclonal antibodies when testing DAT-positive samples, both
      sensitized and CDP-treated RBCs were tested with these monoclonal antibodies by
      the IAT using anti-mouse IgG. No discrepancies were noted with the unsensitized,
      sensitized, or CDP-treated RBCs. An exception was noted with a potent autoanti-I,
      where direct agglutination of the sensitized RBCs was obtained. This study
      demonstrates the value of using murine monoclonal antibodies to determine the
      phenotype of RBCs with a positive DAT caused by autoantibodies (e.g., in
      autoimmune hemolytic anemia) and supports previous studies showing that RBCs
      sensitized in vivo can be typed without chemical manipulation.

PMID- 17430075
TI  - Case report: moderate hemolytic disease of the newborn due to anti-G.
AB  - Views expressed in this article are those of the author and do not reflect the
      official policy or position of the Department of the Navy, Department of Defense,
      or U.S. Government. The only previously published case of anti-G in a pregnant
      woman indicated that anti-G alone caused little, if any, fetal or neonatal
      hemolysis. This report describes an affected fetus with amnionitic fluid OD 450
      absorbance values in the moderate zone of the Liley prediction graph who required
      prolonged phototherapy after birth until day of life 20. Anti-G was identified
      and anti-C and -D excluded in the mother's serum. In contrast to the previous
      report, this report shows anti-G alone can cause moderate HDN and that fetal
      monitoring and treatment may be necessary.

PMID- 17430076
TI  - Review: molecular basis of MNS blood group variants.
AB  - The MNS blood group antigens are expressed in the RBC membrane on glycophorin A
      (GPA), glycophorin B (GPB), or combinations of both. GPA expresses the M or N
      antigen, whereas GPB expresses the S or s antigen and the N antigen ('N'). Both
      glycophorin genes (GYPA and GYPB) are located on the long arm of chromosome 4 and
      share 95 percent sequence identity. This high degree of sequence identity,
      together with the rare involvement of a third homologous gene (GYPE), provides an
      increased chance of recombination, resulting in hybrid molecules that often carry
      one or more novel antigens. Some of the antigens in the MNS system result from a
      single nucleotide substitution. The MNS blood group system now consists of more
      than 40 distinct antigens. This review summarizes the molecular basis associated
      with some of the antigens in the MNS blood group system.

PMID- 17430077
TI  - Chimerism and mosaicism are important causes of ABO phenotype and genotype
      discrepancies.
AB  - Discrepancies between blood group genotype and RBC phenotype are important to
      recognize when implementing DNA-based blood grouping techniques. This report
      describes two such cases involving the ABO blood group in the Korean population.
      Propositus #1 was a 22-year-old healthy man undergoing pretransfusion testing for
      minor surgery. Propositus #2 was a 23- year-old male blood donor. RBCs from both
      propositi were determined to be group AB and demonstrated unusual agglutination
      patterns on forward typing, which were inconsistent with their ABO genotype
      determined by allele-specific (AS) PCR. RBCs from propositus #1 demonstrated
      mixed field agglutination with both anti-A and -B, while RBCs from propositus #2
      demonstrated mixed field only with anti-A reagents. Both had B/O genotypes by AS
      PCR. Cloning and sequencing of ABO exons 6 and 7 revealed three alleles in both
      propositi: propositus #1: A102/B101/O04; propositus #2: A102/B101/O01. A panel of
      nine short-tandem repeat (STR) loci was tested on DNA extracted from blood,
      buccal mucosal cells, and hair from the propositi and on DNA isolated from their
      parents' blood. In all tissues tested from propositus #1, three loci demonstrated
      a double paternal and a single maternal DNA contribution, indicating that he was
      a chimera or a mosaic; in those from propositus # 2, one STR locus demonstrated a
      double paternal DNA contribution, indicating that he was a tetragametic chimera.
      Chimerism and mosaicism are uncommon but important causes of ABO genotype and
      phenotype discrepancies. The evaluation of patients and donors with unusual or
      unexpected serology in pretransfusion testing and consensus ABO alleles may
      include the evaluation of STR loci to detect these phenomena.

PMID- 17430078
TI  - Update on HDFN: new information on long-standing controversies.
AB  - Hemolytic disease of the fetus and newborn (HDFN) results from maternal IgG
      antibodies that cross the placenta to the fetal circulation during gestation and
      cause RBC destruction and complications before birth (HDF), or anemia and
      hyperbilirubinemia after birth (HDN), or both. In its most severe form,HDF
      produces hydrops fetalis, which is characterized by total body edema,
      hepatosplenomegaly, and heart failure and can lead to intrauterine death. Before
      discovery of Rh immunoglobulin (RhIG), HDFN from anti-D was a significant cause
      of perinatal mortality or long-term disability. Routine administration of RhIG to
      D- women during pregnancy and shortly after the birth of D+ infants effectively
      reduced the incidence of HDFN caused by anti-D. Maternal alloimmunization to
      other RBC antigens in the Rh, Kell, and other blood group systems can not be
      routinely prevented and these antibodies can also cause HDFN. Advances in
      prenatal care, noninvasive monitoring, and intrauterine transfusion have improved
      the outlook for affected pregnancies to the extent that even hydrops fetalis can
      be reversed and effectively treated in many cases. This review will provide an
      update on the current issues in prevention and treatment of HDFN, emphasizing
      recent insights into long-standing controversies regarding maternal weak D
      phenotypes and D alloimmunization, noninvasive fetal diagnosis and monitoring of
      affected pregnancies, and recent treatment guidelines.

PMID- 17430079
TI  - In search of the Holy Grail: comparison of antibody screening methods.
AB  - Currently, the goal of testing for RBC antibodies is to use a method that will
      detect, if possible, all antibodies that are considered clinically significant
      and yet not detect antibodies of little clinical importance in transfusion or
      pregnancy. The focus of test method development has been on the more controllable
      variables of the first and second stages of agglutination. Tube test methods have
      been developed over the years to achieve shorter turnaround times for quicker
      test results and improved sensitivity,with the occasional negative impact on
      relevant results. The focus on improving efficiency through automation, and
      personnel resourcing challenges of the transfusion service, have led laboratories
      to select methods tailored to meet their needs. This review compares the newer
      methods used in the gel test and solid phase test with commonly used tube
      methods. Both of the newer methods were developed with future adaptation to
      automation in mind. Further literature reviews about antibodies detected in only
      one or two methods and their general lack of clinical relevance as well as the
      occasional rare examples that produce significant clinical effects on transfused
      patients are also discussed.

PMID- 17430080
TI  - Caring for Australia's most remote communities: obstetric services in the Indian
      Ocean Territories.
AB  - INTRODUCTION: The Indian Ocean Territories (IOT) comprising Christmas and Cocos
      (Keeling) Islands are situated over 2500 km from Perth, Australia, and are
      accessible by commercial aircraft only twice a week. The IOT Health Service
      (IOTHS) is administered from the Department of Transport and Regional Services in
      Canberra, ACT, Australia. Since 1998, all pregnant women have been required to
      leave the islands by 36 weeks gestation and travel to the mainland for birthing.
      Previously most women with low risk pregnancies were delivered on their island.
      Women and their partners regularly question medical staff as to reasons for the
      current obstetric service and, in particular, why they have to leave the Islands
      to give birth. While this is a common scenario in many remote parts of Australia,
      the vast distance involved and the cultural differences of the predominantly
      Chinese and Malay population make the IOT situation unique. METHODS: A study was
      conducted during 2005 to determine the requirements for providing a safe, cost
      effective and socially-acceptable obstetrics service, and to identify possible
      areas for improvement in the current service, and to explore potential solutions.
      This article presents one aspect of the study, involving qualitative analysis of
      recorded interviews with 28 of the islands' women. RESULTS: Having choice about
      where the baby would be born was the most significant category of data analysis.
      In making choice, a number of variables come into play, including positive and
      negative social, economic, logistical and cultural factors related to the
      decision. Women were also strongly influenced by issues of safety, and their
      response to these issues was largely based on their previous experience and
      understanding of the IOT obstetric service. CONCLUSION: Many families expressed a
      desire for full obstetric services to be reinstated on the islands for low-risk
      pregnancies, particularly because of the difficulties they experience with the
      current service. Three recommendations were formulated in response to the social,
      economic, cultural and logistical difficulties faced by IOT women and their
      families.

PMID- 17430081
TI  - Making a difference: education and training retains and supports rural and remote
      doctors in Queensland.
AB  - INTRODUCTION: Access to appropriate continuing medical education (CME)
      opportunities has been identified by many researchers as a key factor in
      retaining medical practitioners in rural and remote communities. There has,
      however, been very little research that has measured the actual effectiveness of
      CME programs on retention. The purpose of this article is to provide some
      evidence as to the efficacy of rurally relevant CME programs in retaining medical
      practitioners in rural and remote communities. METHODS: Evaluation data provided
      by 426 to 429 CME workshop attendees over a 3 year period has been aggregated to
      explore participants' perceptions as to whether access to CME has been effective
      in increasing their confidence in practising in rural and remote communities,
      reducing professional isolation and increasing commitment to remain in rural
      practice. RESULTS: Data from 429 respondents suggest that 94% agree or strongly
      agree that access to CME contributes to confidence in practising in rural and/or
      remote locations. Similarly, data suggest that 93% of respondents (n = 427) agree
      or strongly agree that access to CME alleviates professional isolation. When
      asked whether they were less likely to remain in rural practice without access to
      CME, 80% of respondents (n = 426) agreed or strongly agreed that they were less
      likely to remain without access. CONCLUSION: The provision of CME based on the
      expressed needs of rural and remote medical practitioners tends to be well
      received and highly valued by workshop respondents. We suggest that professional
      support through the provision of rurally relevant workshop-delivered CME is an
      effective strategy in retaining doctors in rural and remote communities.

PMID- 17430082
TI  - What does it take? The influence of rural upbringing and sense of rural
      background on medical students' intention to work in a rural environment.
AB  - INTRODUCTION: There is abundant evidence that rural origin is an influence on
      rural career choice. Rural origin is widely used to select students to be
      supported into programs designed to address the rural medical workforce shortage.
      What is not as clear is how many years of rural upbringing are required to have a
      maximal effect on rural career choice. Neither is the place of having a sense of
      rural background well understood. METHODS: A cross-sectional self-completed paper
      based survey of all students in years one through four of the Monash University
      medical course was undertaken in 2003. The survey included a scale to measure
      stated rural career intention as well as questions about the number of years of
      rural upbringing and whether students had a sense of rural background. The Rural
      Intention score was divided into three categories: strong urban intent, strong
      rural intent, and an intermediate, less certain intent. RESULTS: There was an 88%
      (n = 399) response rate from students holding Commonwealth Supported Places.
      Approximately 30% of these claimed a sense of rural background, and 28% had more
      than 8 years of rural upbringing. Twenty-five percent stated a strong intention
      to choose a rural career and 34.5% had strong urban intent. The remaining 40.5%
      were in the intermediate group. Almost all students (97.5%) with over 5 years of
      rural upbringing had developed a sense of rural background, and almost all
      (97.5%) with less than 5 years' rural upbringing denied a sense of rural
      background. Rural intent was high for those with a sense of rural background and
      those with more than 8 years of rural upbringing, but the students who had had
      from 4 to 8 years of rural upbringing mainly fell into the 'uncertain' category.
      DISCUSSION: In this cohort of almost 400 Australian medical students, a sense of
      rural background developed at a clear point, around 5 years of rural upbringing.
      Students with a sense of rural background were likely to develop a strong rural
      intent several years before similar students who had failed to make this
      connection with a rural community. This latter group displayed uncertainty toward
      a rural career choice, possibly due to unfamiliarity. Unlike those with strong
      urban intent, these students have not excluded a rural career and should be
      supported. The inclusion of a measure of the intention of students to work in a
      rural environment is likely to increase the reliability and validity of selection
      procedures.

PMID- 17430083
TI  - Design of health care technologies for the developing world.
AB  - Approximately 20 years ago, the international community embarked on a project to
      bring health care to everyone by the year 2000 featuring, among other things,
      technologies that were known to be effective and economical. It was largely a
      failure. In fact, health care deteriorated in many of the target nations.
      Problems such as public mistrust, lack of spare parts, lack of required
      consumables, lack of reliable power and water, lack of public infrastructure such
      as roads, lack of technical expertise, and other problems plague health care
      technology in the developing world. Biomedical engineers are just beginning to
      quantify and address the barriers to technology unique to the developing world.
      This article reviews the barriers, both real and perceived, to the introduction
      of health care technology with a main focus on health care technology in
      hospitals.

PMID- 17430084
TI  - The clockwork of metabolism.
AB  - The observation that cycles of sleep and wakefulness occur with a periodicity
      fixed in time to match the rotation of the Earth on its axis provided a key to
      unlock the first genetic code for a neurobehavioral pathway in flies and
      ultimately in mice. As a remarkable outcome of this discovery, we have gained an
      unprecedented view of the conserved genetic program that encodes a sense of time
      across all kingdoms of life. The tools are now in hand to begin to understand how
      important processes such as energy homeostasis and fuel utilization are
      coordinated to anticipate daily changes in environment caused by the rising and
      setting of the sun. A better understanding of the impact of circadian gene
      networks on nutrient balance at the molecular, cellular, and system levels
      promises to shed light on the emerging association between disorders of diabetes,
      obesity, sleep, and circadian timing.

PMID- 17430085
TI  - The genetics of anorexia nervosa.
AB  - Anorexia nervosa is a perplexing illness marked by low body weight and persistent
      fear of weight gain. Anorexia nervosa has the highest mortality rate of any
      psychiatric disease. Historically, anorexia nervosa was viewed as a disorder
      primarily influenced by sociocultural factors; however, over the past decade,
      this perception has been challenged. Family studies have consistently
      demonstrated that anorexia nervosa runs in families. Twin studies have
      underscored the contribution of additive genetic factors to the observed familial
      aggregation. With these bodies of literature as a starting point, we evaluate
      critically the current state of research on molecular genetic studies of anorexia
      nervosa and provide guidance for future research.

PMID- 17430086
TI  - Creatine: endogenous metabolite, dietary, and therapeutic supplement.
AB  - Creatine and phosphocreatine serve not only as an intracellular buffer for
      adenosine triphosphate, but also as an energy shuttle for the movement of high
      energy phosphates from mitochondrial sites of production to cytoplasmic sites of
      utilization. The spontaneous loss of creatine and of phosphocreatine to
      creatinine requires that creatine be continuously replaced; this occurs by a
      combination of diet and endogenous synthesis. Vegetarians obtain almost no
      dietary creatine. Creatine synthesis makes major demands on the metabolism of
      glycine, arginine, and methionine. Large doses of creatine monohydrate are widely
      taken, particularly by athletes, as an ergogenic supplement; creatine supplements
      are also taken by patients suffering from gyrate atrophy, muscular dystrophy, and
      neurodegenerative diseases. Children with inborn errors of creatine synthesis or
      transport present with severe neurological symptoms and a profound depletion of
      brain creatine. It is evident that creatine plays a critical, though
      underappreciated, role in brain function.

PMID- 17430087
TI  - Flax rust resistance gene specificity is based on direct resistance-avirulence
      protein interactions.
AB  - Genetic studies of the flax-flax rust interaction led to the formulation of the
      gene-for-gene hypothesis and identified resistance genes (R) in the host plant
      and pathogenicity genes, including avirulence (Avr) and inhibitor of avirulence
      genes (I), in the rust pathogen. R genes have now been cloned from four of the
      five loci in flax and all encode proteins of the Toll, Interleukin-1 receptor, R
      gene-nucleotide binding site-leucine-rich repeat (TIR-NBS-LRR) class. Avr genes
      have been cloned from four loci in flax rust and encode small secreted proteins
      with no between locus similarity and no close homologs in current data bases. It
      is postulated that Avr proteins enter the host cell, have virulence effector
      functions, and in resistant host genotypes, are recognized by direct and specific
      interaction with host R proteins, leading to activation of rust resistance
      defense responses. Direct interaction between R and Avr proteins is the basis of
      gene-for-gene specificity in the flax-flax rust system and both R and Avr genes
      have the signatures of diversifying selection, suggesting the existence of a
      coevolutionary arms race between the host plant and its obligate rust pathogen.

PMID- 17430088
TI  - High-efficiency promoter-dependent transduction by adeno-associated virus type 6
      vectors in mouse lung.
AB  - The transduction efficiency of adeno-associated virus (AAV) vectors in various
      somatic tissues has been shown to depend heavily on the AAV type from which the
      vector capsid proteins are derived. Among the AAV types studied, AAV6 efficiently
      transduces cells of the airway epithelium, making it a good candidate for the
      treatment of lung diseases such as cystic fibrosis. Here we have evaluated the
      effects of various promoter sequences on transduction rates and gene expression
      levels in the lung. Of the strong viral promoters examined, the Rous sarcoma
      virus (RSV) promoter performed significantly better than a human cytomegalovirus
      (CMV) promoter in the airway epithelium. However, a hybrid promoter consisting of
      a CMV enhancer, beta-actin promoter and splice donor, and a beta-globin splice
      acceptor (CAG promoter) exhibited even higher expression than either of the
      strong viral promoters alone, showing a 38-fold increase in protein expression
      over the RSV promoter. In addition, we show that vectors containing either the
      RSV or CAG promoter expressed well in the nasal and tracheal epithelium.
      Transduction rates in the 90% range were achieved in many airways with the CAG
      promoter, showing that with the proper AAV capsid proteins and promoter
      sequences, efficient transduction can be achieved.

PMID- 17430089
TI  - Real-time detection of stress in 3D tissue-engineered constructs using NF-kappaB
      activation in transiently transfected human dermal fibroblast cells.
AB  - The main objective of this study was to develop a nondestructive reporter system
      for assessing the response of human cells contained within a three-dimensional
      (3D) tissue-engineered construct to exogenous stress. Dermal fibroblasts were
      transiently transfected with a reporter construct linked to nuclear factor kappaB
      (NF-kappaB) activation which led to expression of a nonstable form of enhanced
      green fluorescent protein (d2EGFP) after stimulation. This led to a temporary
      production of fluorescence, which could be readily detected but was not
      intrinsically toxic, as cells were able to metabolize the initial cycle of d2EGFP
      produced. This permitted the model to be used for restimulation post recovery. To
      investigate the performance and predictive ability of this method for assessing
      cellular response to stress in 3D, we used a range of compounds known to have pro
      inflammatory or oxidative properties. Tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-1-beta (IL-1beta) were selected for having a direct cytokine action;
      lipopolysaccharide (LPS) was selected for modeling bacterial-mediated
      inflammation; and hydrogen peroxide was selected as a crude method for delivering
      an oxidative stress. Transfected cells were stimulated with the above compounds
      in 3D and the synthesis of d2EGFP was detected as a measure of NF-kappaB
      activation. The resultant fluorescence was scored using a series of
      photomicrographs taken by epifluorescence microscopy. All agents activated NF
      kappaB when cells were grown in 3D scaffolds but did not cause any significant
      reduction in cell viability as measured by a standard MTT-ESTA viability test.
      Parallel NF-kappaB activation and MTT measurements was also conducted in two
      dimension (2D) and confirmed findings in 3D. The 3D model described using a
      fluorescent reporter gene is a highly sensitive and reliable method for detecting
      cellular stress and represents a key step in developing tissue engineering models
      with the potential for screening pharmaceutical and cosmetic compounds, as an
      alternative to existing in vitro and in vivo methods.

PMID- 17430090
TI  - Review: mineralization of synthetic polymer scaffolds for bone tissue
      engineering.
AB  - It has repeatedly been shown that demineralization improves the ability of bone
      auto- and allografts to regenerate natural bone tissue. Conversely, much work in
      the field of bone tissue engineering has used composite materials consisting of a
      mineralized phase or materials designed to mineralize rapidly in situ. In this
      review, we seek to examine these disparate roles of mineralization and the
      underlying factors that cause this discordance and to examine methods and
      principles of the mineralization of synthetic polymer scaffolds. Biomimetic
      approaches to mineralization and phosphorus-containing materials are highlighted,
      and a brief section focusing on drug-delivery strategies using mineralized
      scaffolds is included.

PMID- 17430091
TI  - Molecular architectonic on metal surfaces.
AB  - The engineering of highly organized systems from instructed molecular building
      blocks opens up new vistas for the control of matter and the exploration of
      nanodevice concepts. Recent investigations demonstrate that well-defined surfaces
      provide versatile platforms for steering and monitoring the assembly of molecular
      nanoarchitectures in exquisite detail. This review delineates the principles of
      noncovalent synthesis on metal substrates under ultrahigh vacuum conditions and
      briefly assesses the pertaining terminology-self-assembly, self-organization, and
      self-organized growth. It presents exemplary scanning-tunneling-microscopy
      observations, providing atomistic insight into the self-assembly of organic
      clusters, chains, and superlattices, and the metal-directed assembly of low
      dimensional coordination architectures. This review also describes hierarchic
      assembly protocols leading to intricate multilevel order. Molecular architectonic
      on metal surfaces represents a versatile rationale to realize structurally
      complex nanosystems with specific shape, composition, and functional properties,
      which bear promise for technological applications.

PMID- 17430092
TI  - Bending mechanics and molecular organization in biological membranes.
AB  - The underlying structure of cell membranes consists of a highly heterogeneous
      fluid lipid bilayer. Within this milieu, complexes of proteins transiently
      assemble and dissolve in the performance of the functions of life. The length
      scales of these coordinated spatial rearrangements can approach the size of the
      cell, itself, enabling direct visualization in some cases with tantalizing
      clarity. There has been much interest in the physical driving forces responsible
      for the assembly of organized structures in cell membranes. Cholesterol-mediated
      miscibility phase separation within the lipid bilayer has attracted enormous
      attention over the past decade. This, however, is not the only ordering principle
      at play. In the following sections, I review recent experimental observations of
      bending-mediated force transduction and molecular organization in lipid
      membranes. These results have emerged largely from new experimental
      methodologies, which are discussed in parallel.

PMID- 17430093
TI  - The ambivalent nature of T-cell infiltration in the central nervous system of
      patients with multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous
      system (CNS) of presumed autoimmune origin. On the basis of the pathophysiology
      of MS, inflammatory reactions in the CNS are considered detrimental. Recent
      evidence suggests that the injured CNS can also benefit from immune activity. In
      this review, we will first provide an overview of the mechanisms by which immune
      cells contribute to CNS injury in MS. We will further review evidence supporting
      a neuroprotective role of CNS inflammation with special focus on the protective
      properties of autoimmune reactions. Finally, we discuss the proposed mechanisms
      by which autoreactive T cells exert protection in the CNS and how this protection
      is regulated.

PMID- 17430094
TI  - Mast cell homeostasis: a fundamental aspect of allergic disease.
AB  - Mast cells are well known for their role in allergic disease and have recently
      been implicated in inflammatory disorders, including autoimmune arthritis,
      multiple sclerosis, and atherosclerosis. Although aberrant mast cell activation
      is the focus of many studies, much less is known about normal mast cell
      homeostasis. Because loss of the normal constraints on mast cell activation,
      proliferation, and survival may be central to disease etiology, understanding
      these issues warrants attention. This review summarizes the knowledge of mast
      cell homeostasis controlled by IgE and the regulatory cytokines IL-4, IL-10, and
      TGF-beta1. Because each of these proteins plays an important role in immune
      responses tied to mast cell-associated disease, this group represents a potential
      set of factors altered in atopic or autoimmune patients. It is interesting to
      note, for example, that polymorphisms within each of these factors or their
      receptors are linked to allergic disease. By first understanding how cytokines
      and IgE regulate mast cell function and survival, we may then predict how these
      factors may function in disease onset and progression.

PMID- 17430095
TI  - Autoimmune etiology in chronic prostatitis syndrome: an advance in the
      understanding of this pathology.
AB  - The prostate is the target of many inflammatory and neoplastic disorders that
      affect men of all ages. Pathological conditions of the prostate gland range from
      infection of this organ by ascending bacteria from infected urine, to chronic
      prostatitis/chronic pelvic pain syndrome (CP/CPPS) of a still unknown etiology
      (accompanied with inflammation and lymphocyte infiltration of the gland), to
      benign hyperplasia and cancer. Patients under 50 years of age usually suffer from
      CP/CPPS, a chronic inflammatory syndrome characterized by pelvic pain, irritative
      voiding symptoms, and sexual dysfunction complaints. In this review, we summarize
      the current knowledge regarding immunological alterations present in CP/ CPPS
      patients. Remarkably, an inflammation state, in the absence of an invading
      infectious agent, is established in these patients, suggesting that an autoimmune
      process could be involved. In fact, specific autoimmune response to prostate
      antigens has recently been reported in CP/CPPS patients. Autoimmune response to
      prostate gland affects the seminal quality reported in these patients and may
      have critical consequences in their fertility. It is anticipated that preclinical
      studies in experimental models for CP/CPSS will provide important insights into
      the etiopathogenic mechanisms involved in this disease. We discuss here the
      similarities and the differences between human disease and experimental models
      and argue for the importance of the prostate gland in male reproductive function.
      Ultimately, we suggest that a state of inflammation, originally incited by an
      autoimmune response within the prostate, together with a diminished prostate
      functionality, may compromise male fertility.

PMID- 17430096
TI  - MHC-restricted B-cell antigen presentation in memory B-cell maintenance and
      differentiation.
AB  - Memory B-cell development, maintenance, and differentiation have been believed to
      be tightly regulated by T cells through major histocompatibility complex (MHC)-II
      restricted cognate interaction. However, recent studies have indicated that
      memory B cells are a heterogeneous population with various ontogeny and with
      derivations from T-cell-independent as well as T-cell-dependent response. In
      addition, several studies highlight T-cell-independent maintenance and
      differentiation of memory B cells by innate polyclonal stimuli associated with
      Toll-like-receptors (TLRs). Thus, both T-cell-dependent and T-cell-independent
      mechanisms with possibly different physiological functions are required for
      maximal memory B-cell maintenance and differentiation. In this review, we discuss
      the mechanisms of memory B-cell maintenance and differentiation by re-examining
      the requirement for MHC-II-restricted B-cell antigen presentation based on our
      recent study in a mouse model that lacks MHC-II on memory B cells. We propose
      that MHC-II-restricted memory B-cell maintenance and differentiation are the
      indispensable mechanisms by which we achieve health and the maximum quality of
      memory response with specific antibody production, while preventing plasma cell
      differentiation from self-reactive memory B cells under the control of T-helper
      cells and possibly regulatory T cells.

PMID- 17430097
TI  - Naturally occurring regulatory T cells: recent insights in health and disease.
AB  - Development of naturally occurring CD4+CD25+ T regulatory cells (Treg) in the
      thymus requires the transcription factor Foxp3. Major histocompatibility complex
      (MHC) class II, self-ligands expressed by epithelial cells, and thymic stromal
      lymphopoietin also appear to play important roles. In addition, several molecular
      regulators of T-cell receptor (TCR) signaling (both positive and negative) have
      been implicated in the control of Treg development. Foxp3 is a transcriptional
      repressor of IL-2 and other cytokines and appears to maintain the anergic and
      suppressor function of these cells. Multiple cell types (T cells, B cells,
      dendritic cells [DC], and natural killer [NK] cells) are targeted by Treg using
      diverse suppressor mechanisms, whereas factors that regulate Treg proliferation
      and function, including Toll-like receptor (TLR) ligands, have also been
      identified. Because Treg play an important role in the control of autoimmunity,
      therapeutic strategies are being pursued to enhance their numbers and function in
      specific autoimmune diseases. In transplantation, where Treg also offer potential
      for therapy of rejection and graft-versus-host disease (GVHD), indirect
      allorecognition may be the dominant pathway for immune regulation by these cells.
      In tumor immunology, Treg have emerged as major suppressors of T-cell-mediated
      antitumor responses and represent a significant obstacle to effective anticancer
      vaccines. Strategies aimed at depletion/functional inhibition of these cells by
      molecular targeting must maintain a critical balance between tumor immunity and
      self-tolerance.

PMID- 17430098
TI  - Pharmaceutical approaches to preparing pelletized dosage forms using the
      extrusion-spheronization process.
AB  - Pelletized dosage forms date back to the 1950s, when the first product was
      introduced to the market. Since then, these dosage forms have gained considerable
      popularity because of their distinct advantages, such as ease of capsule filling
      because of better flow properties of the spherical pellets; enhancement of drug
      dissolution; ease of coating; sustained, controlled, or site-specific delivery of
      the drug from coated pellets; uniform packing; even distribution in the GI tract;
      and less GI irritation. Pelletized dosage forms can be prepared by a number of
      techniques, including drug layering on nonpareil sugar or microcrystalline
      cellulose beads, spray drying, spray congealing, rotogranulation, hot-melt
      extrusion, and spheronization of low melting materials or extrusion
      spheronization of a wet mass. This review discusses recent developments in the
      pharmaceutical approaches that have been used to prepare pelletized dosage forms
      using the extrusion-spheronization process over the last decade. The review is
      divided into three parts: the first part discusses the extrusion-spheronization
      process, the second part discusses the effect of varying formulation and process
      parameters on the properties of the pellets, and the last part discusses the
      different approaches that have been used to prepare pelletized dosage forms using
      the extrusion-spheronization process.

PMID- 17430099
TI  - Lipid-based cochleates: a promising formulation platform for oral and parenteral
      delivery of therapeutic agents.
AB  - Cochleates are lipid-based supramolecular assemblies that display great potential
      as delivery systems for systemic delivery of drugs, including peptides, proteins,
      vaccines, oligonucleotides, and genes. This is mainly attributed to their high
      stability and biocompatibility and their ability to deliver both hydrophilic and
      lipophilic drugs. Cochleates have a unique multilayered spiral structure, which
      is composed of a negatively charged phospholipid and a divalent cation, and can
      encapsulate diverse drug molecules of various shapes and sizes while minimizing
      toxicity associated with polymeric materials present in micro- and nanoparticle
      systems. This review describes current technological advances in the preparation
      methods, physicochemical characterization, and potential applications of
      cochleates as a drug delivery system for systemic delivery of various types of
      therapeutic agents.

PMID- 17430100
TI  - Oral colon-specific drug delivery of protein and peptide drugs.
AB  - With the advent of new technologies and radical growth in the field of
      biotechnology, dozens of protein and peptide drugs have been marketed. However,
      there are several challenges for successful delivery of such molecules. A number
      of routes have been used for the delivery of these fragile molecules by exploring
      various novel delivery technologies, including microspheres, liposomes, gel
      spheres, nano-spheres, niosomes, microemulsions, use of permeation enhancers, use
      of protease inhibitors, etc. But the route that has attracted the attention of
      worldwide drug delivery scientists is the oral route due to its various
      advantages. Even though the proteolytic activity is higher in a few segments of
      the gastrointestinal tract (GIT), this route has certain segments that have lower
      proteolytic activity, for example, the colon. The colon has captured attention as
      a site for the delivery of these molecules because of its greater responsiveness
      to absorption enhancers, protease inhibitors, and novel bioadhesive and
      biodegradable polymers. Although the success rate of these approaches, when used
      alone is pretty low, when used in combinations, these agents have demonstrated
      wonders in increasing the drug bioavailability. This review focuses on the
      challenges, pharmaceutical concepts, and approaches involved in the delivery of
      these fragile molecules, specifically to the colon. This review also includes
      studies conducted on colonic targeting of such drugs. Further studies may lead to
      improvements in therapy using protein/peptide drugs and refinements in the
      technology of colon-specific drug delivery.

PMID- 17430101
TI  - Monoclonal antibody therapies targeting pancreatic ductal adenocarcinoma.
AB  - Pancreatic ductal adenocarcinoma (PDA) is a lethal disease with a poor prognosis
      where incidence mirrors mortality. Gemcitabine and gemcitabine plus erlotinib
      (epidermal growth factor receptor tyrosine kinase inhibitor) are the only FDA
      approved therapies for unresectable or metastatic PDA and are at best palliative.
      Hence, considerable efforts have been initiated to identify novel targets for
      monoclonal antibody (Mab) therapies that may safely and effectively be combined
      with gemcitabine. Mabs to cell surface receptors and/or their ligands have shown
      efficacy in pre-clinical and clinical studies in both solid and hematological
      malignancies and can safely be given with chemotherapy. A number of clinical
      trials have evaluated the safety and efficacy of Mabs targeting the tumor and/or
      tumor micro-environment and in combination with chemotherapy for PDA with very
      little success. Here we review the rationale for Mab therapies, targeted clinical
      trials, rational basis for target selection, pre-clinical models and promising
      novel cell surface targets and/or growth factor ligands that are amenable to
      ongoing and future Mab therapies that hold promise and hope for patients and
      their families with this devastating disease.

PMID- 17430102
TI  - Engineered tissue as a model to study cell and tissue function from a biophysical
      perspective.
AB  - Cells, tissues and organs function in a three-dimensional (3D) environment.
      Ideally, cell-based models that capture both the 3D organization and multi
      cellular complexity of the native system provide the most powerful tools for
      screening the effects of therapeutic candidates. This approach to drug discovery
      bridges tissue engineers, who are constructing 3D tissues, with biologists, who
      are studying healthy versus diseased states and to pharmacologists, who are
      developing screening assays. Within this context, an innovative biophysical
      perspective of tissue morphogenesis, malignancy and treatment responsiveness has
      been established recently. Numerous experimental studies have shown that
      mechanical loading regulates the anabolic and catabolic metabolism of cells.
      Anabolic mechanisms, in particular, are of vital importance in the process of
      tissue engineering, which is of increasing scientific and clinical interest.
      Cells seeded and cultured in appropriate constructs should be mechanically
      stimulated to produce and to structure the required constituents of the
      extracellular matrix. However, the determination of the most effective type of
      loading, the appropriate load history and the mechanical field variables
      responsible for the stimulation of the cell activity, as well as the pathways of
      communication among cells, are still subject of contrary discussions and
      motivation of recent investigation. In this review we discuss the tissue-level
      response to mechanical signalling, we provide an overview of prominent techniques
      currently used for exerting mechanical stresses on engineered tissue and an
      overview of numerical mechanics studies providing information on mechanical field
      variables potentially triggering the biological activity.

PMID- 17430103
TI  - Pathway analysis for design of promiscuous drugs and selective drug mixtures.
AB  - The decrease in the drug approval rate by the FDA and the recent failure of some
      blockbuster drugs has prompted a re-examination of the focus of the
      pharmaceutical industry on increasing drug selectivity. As a result, it has been
      proposed that the most efficient cure is in developing promiscuous drugs and
      selective drug mixtures. Rational design of drug mixtures has been nearly
      impossible due to the lack of information about in vivo cell regulation,
      mechanisms of pathway activation, and interactions between different pathways in
      vivo. We review the current state of the art for rational design of combination
      therapy and argue that the current industry-wide development of the
      infrastructure for pathway analysis provides unprecedented opportunity for the
      rational design of multicomponent and multifunctional drugs. We propose several
      ways how to use pathway analysis to rationally combine known drugs for either
      synergizing their efficacy or suppressing individual side effects.

PMID- 17430104
TI  - Formulation of transdermal drug delivery system: matrix type, and selection of
      polymer- their evaluation.
AB  - Goatskin is used instead of rat-skin to study the permeation and the results are
      compared. The percentage of permeation is double in goatskin. We have five
      different oils to study, how they influence permeation and all of them have
      improved permeation when used on goatskin. To analyze further two parameters
      percentage and rate of permeation are used. When these five oils are used with
      salicyclic acid on goatskin the following results are obtained. The percentage of
      permeation is as follows [Caraway oil (48%) > Lemon oil (36%) > Peppermint oil
      (29%) > Lemon Grass oil (22%) > Citronella oil (19%)]. The caraway oil has the
      highest percentage of permeation whereas citronella oil has the lowest percentage
      of permeation. Caraway oil has three times more permeation than that of
      citronella oil. The selection of polymer for the formulation of TDDS was done
      basing on a comparative study of five polymers and their various combinations
      using such parameters as uniformity of weight, thickness and content and
      percentage and rate of diffusion counted. Results show that methylcellulose and
      hydroxy propyl methyl cellulose record more control release of salicyclic acid
      than the other polymers. Except HPMC all other polymers follow zero order
      kinematics. Basing on this experimental evidence transdermal patch of salicyclic
      acid was formed with HPMC, MC polymer incombination with caraway oil has
      permeating enhancer and evaluated using goatskin. Comparative study shows that
      there is two fold increases in the percentage of permeation.

PMID- 17430106
TI  - The human indoleamine 2,3-dioxygenase gene and related human genes.
AB  - Tryptophan oxidation occurs via both extra-hepatic and hepatic pathways. Although
      these pathways share many enzymes, the first and rate-limiting step in each
      pathway is carried out by two different enzymes: Indoleamine-Pyrrole 2,3
      Dioxygenase (INDO) and Tryptophan 2,3-Dioxygenase (TDO2). Over the course of the
      last forty years extensive and detailed research by many groups have led to an
      understanding of some of the important biologic functions of these pathways and
      their metabolic products. One of the tasks that now lie ahead is linking
      variations in these genes with variable human responses in different disease
      states. This short review will focus on known aspects of the INDO and TDO2 gene
      structure and variability. In addition to INDO and TDO2 a third related gene, the
      Indoleamine-Pyrrole 2,3 Dioxygenase-like 1 (INDOL1) gene will be discussed.
      INDOL1 is a gene of unknown function that lies adjacent to INDO on chromosome 8.

PMID- 17430107
TI  - Substrate and cofactor requirements of indoleamine 2,3-dioxygenase in interferon
      gamma-treated cells: utilization of oxygen rather than superoxide.
AB  - Much attention has been paid in initial biochemical studies on the ability of
      indoleamine 2,3-dioxygenase to use superoxide as substrate to cleave tryptophan
      to N-formyl kynurenine. This ability, however, is limited to the ferric form of
      the enzyme only, whereas the ferrous form requires oxygen rather than superoxide
      as substrate. As long as the enzyme is held in the ferrous form, high yield
      formation of product proceeds from the ferrous oxygen tryptophan ternary complex
      without the participation of superoxide. Enzyme assays in homogenates are carried
      out in presence of Methylene Blue, ascorbate and catalase. Ascorbate can be
      replaced by other reductants like e.g. tetrahydrobiopterin. Experiments with
      alteration of intracellular tetrahydrobiopterin concentrations in intact
      interferon-gamma treated cells clearly showed that tetrahydrobiopterin is not
      required for the indoleamine 2,3-dioxygenase reaction. In homogenates of
      interferon-gamma treated T-24 cells, substrates of xanthine oxidase did not
      stimulate the indoleamine 2,3-dioxygenase reaction, nor did allopurinol inhibit
      the reaction, nor did superoxide dismutase alter indoleamine 2,3-dioxygenase
      activity irrespective of the reductant used. From these experiments we concluded
      that molecular oxygen rather than superoxide is used in cell homogenates by
      indoleamine 2,3-dioxygenase to cleave L-tryptophan. A detailed analysis of
      available reports on oxygen and superoxide utilization by indoleamine 2,3
      dioxygenase gives a comprehensive picture that the enzyme uses oxygen bound to
      the ferrous enzyme for cleavage of tryptophan, that the enzyme needs to be held
      by reductants in the ferrous state in enzyme incubations, and that superoxide is
      one of the reductants capable performing this reduction.

PMID- 17430108
TI  - Indoleamine 2,3-dioxygenase in materno-fetal interaction.
AB  - The mechanism of maternal immunotolerance of the semiallogeneic fetus has been a
      matter of intense investigation. The tryptophan-degrading enzyme indoleamine 2,3
      dioxygenase (IDO) is reported to be critically implicated. This article discusses
      findings pertaining to the role of IDO in pregnancy, its location at the feto
      maternal interface, systemic induction of IDO in pregnancy and the association of
      IDO to spontaneous abortion and preeclampsia. Whereas there is a large body of
      evidence supporting the relevance of IDO as a key immunoregulatory factor in feto
      maternal tolerance, open questions remain concerning as to its role.

PMID- 17430109
TI  - Tryptophan catabolism in IDO+ plasmacytoid dendritic cells.
AB  - Plasmacytoid dendritic cells (pDCs) represent a specialized cell population that
      produces large amounts of type I interferons, the so-called natural interferon
      producing cells. Recently, murine and human pDCs have been credited with a unique
      ability to express indoleamine 2,3-dioxygenase (IDO) and to mediate
      immunosuppression in specific settings. This suggests an important role for IDO
      expressing pDCs in controlling the balance of inflammation and tolerance. Here we
      review recent advances in our understanding of how these cells may be critical at
      the interface of inflammation and tolerance and discuss the potential for
      therapeutic IDO modulation as an immunoregulatory maneuver targeting pDC
      function.

PMID- 17430110
TI  - How does indoleamine 2,3-dioxygenase contribute to HIV-mediated immune
      dysregulation.
AB  - Infection with the human immunodeficiency virus type 1 (HIV) results in a chronic
      infection that progressively cripples the host immune defenses. HIV infection is
      associated with increased tryptophan (trp) catabolism by the cytokine-inducible
      enzyme indoleamine 2,3-dioxygenase (IDO). IDO has powerful immune suppressive
      activity, which could contribute to the immune dysfunction observed in HIV
      infected patients. In this review we discuss the immune mechanisms that could
      mediate the HIV-induced increase of IDO activity (such as IFN-gamma, IFN-alpha,
      CTLA-4/B7 and direct viral exposure). We then consider the current knowledge of
      IDO-mediated immune suppressive mechanisms with regard to different cell types
      (CD4(+) T cells, CD8(+) T cells, natural killer cells, B cells and regulatory T
      cells), from the perspective of their potential consequences for the HIV-infected
      host. HIV-induced, IDO-mediated trp catabolism may contribute to the perpetuation
      of HIV infection into its chronic phase by dampening efficient immune anti-viral
      responses. Therapeutic approaches aimed at manipulating this powerful immune
      suppressive mechanism might be considered in the setting of HIV infection.

PMID- 17430111
TI  - Indoleamine-2, 3-dioxygenase and other interferon-gamma-mediated pathways in
      patients with human immunodeficiency virus infection.
AB  - Human immunodeficiency virus type 1 (HIV) infection is characterized by
      progressive immunodeficiency despite of an overwhelming cellular immune
      activation. Patients show highly elevated serum/plasma concentrations of the
      proinflammatory cytokine interferon-gamma (IFN-gamma), which induces human
      monocytes to form neopterin, to produce reactive oxygen species (ROS) and in
      parallel, to degrade tryptophan. Enhanced tryptophan degradation by the enzyme
      indoleamine-2, 3-dioxygenase (IDO) contributes importantly to disease progression
      and "complications" of HIV infection: By a subsequent impairment of protein
      metabolism and serotonin formation, the development of neuropsychiatric disorders
      and weight loss in HIV infected patients can be enforced. Furthermore, increased
      IDO-activation efficiently suppresses the growth and proliferation of pathogens
      as well as host T-cells. IDO and other IFN-gamma-mediated pathways are strongly
      induced in patients with HIV infection and are also linked with disease
      progression: Neopterin formation by GTP-cyclohydrolase I sensitively reflects the
      stage of the disease, and determination of the pteridine in body fluids is useful
      to monitor the efficacy of antiretroviral therapy. Neopterin is an independent
      prognostic factor for the outcome of disease, and well suited to estimate the
      degree of immune activation in vivo and the responsiveness of immunocompetent
      cells to stimulation in vitro. ROS formation may contribute to the development of
      oxidative stress in HIV infection, resulting in depletion of antioxidants. The
      cause-effective role of an overwhelming Th1-type immune response together with
      the activation of IDO and other IFN-gamma-mediated biochemical pathways for the
      course of HIV infection, the development of immunodeficiency, anemia and weight
      loss in HIV patients is discussed.

PMID- 17430112
TI  - Role of indoleamine 2,3-dioxygenase in antimicrobial defence and immuno
      regulation: tryptophan depletion versus production of toxic kynurenines.
AB  - Tryptophan metabolism occurs via the protohemoprotein enzymes tryptophan 2,3
      dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), the latter action of
      which has a number of effects in the body including both antimicrobial defence
      and immune regulation. Whilst the antimicrobial action of IDO is largely due to
      depletion of the essential amino acid tryptophan, the immune regulatory function
      of IDO is still unclear and controversial. The list of pathogens that are
      "sensitive" to IDO-mediated tryptophan degradation covers intra-cellular
      parasites such as toxoplasma and possibly plasmodia, viruses (herpes viruses) to
      intra-cellular bacteria (chlamydia and rickettsia) and extra-cellular bacteria
      such as streptococci, enterococci and staphylococci. Immune regulation may be a
      consequence of tryptophan depletion, the accumulation of immune-active or toxic
      metabolites or due to other signalling events. This review covers the latest data
      and controversy pertaining to the antimicrobial and immune regulatory effects of
      tryptophan metabolism.

PMID- 17430113
TI  - Pharmacological targeting of IDO-mediated tolerance for treating autoimmune
      disease.
AB  - Cells at the maternal-fetal interface express indoleamine 2,3 dioxygenase (IDO)
      to consume all local tryptophan for the express purpose of starving adjacent
      maternal T cells of this most limiting and essential amino acid. This stops local
      T cell proliferation to ultimately result in the most dramatic example of immune
      tolerance, acceptance of the fetus. By contrast, inhibition of IDO using 1-methyl
      tryptophan causes a sudden catastrophic rejection of the mammalian fetus.
      Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO
      induction in responsive antigen presenting cells (APCs) also to transmit
      tolerogenic signals to T cells. Thus it makes sense to consider IDO induction
      towards tolerance for autoimmune diseases in general. Approaches to cell specific
      therapeutic IDO induction with NAD precursor supplementation to prevent the
      collateral non-T cell pathogenesis due to chronic TNFalpha-IDO activated
      tryptophan depletion in autoimmune diseases are reviewed. Tryptophan is an
      essential amino acid most immediately because it is the only precursor for the
      endogenous biosynthesis of nicotinamide adenine dinucleotide (NAD). Both
      autoimmune disease and the NAD deficiency disease pellagra occur in women at
      greater than twice the frequency of occurrence in men. The importance of IDO
      dysregulation manifest as autoimmune pellagric dementia is genetically
      illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in
      the IDO antagonizing genes TYROBP/DAP12 or TREM2. Loss of function leads to
      psychotic symptoms rapidly progressing to presenile dementia likely due to
      unchecked increases in microglial IDO expression, which depletes neurons of
      tryptophan causing neurodegeneration. Administration of NAD precursors rescued
      entire mental hospitals of dementia patients literally overnight in the 1930's
      and NAD precursors should help Nasu-Hakola patients as well. NAD depletion
      mediated by peroxynitrate PARP1 activation is one of the few established
      mechanisms of necrosis. Chronic elevation of TNFalpha leading to necrotic events
      by NAD depletion in autoimmune disease likely occurs via combination of
      persistent IDO activation and iNOS-peroxynitrate activation of PARP1 both of
      which deplete NAD. Pharmacological doses of NAD precursors repeatedly provide
      dramatic therapeutic benefit for rheumatoid arthritis, type 1 diabetes, multiple
      sclerosis, colitis, other autoimmune diseases, and schizophrenia in either the
      clinic or animal models. Collectively these observations support the idea that
      autoimmune disease may in part be considered as localized pellagra manifesting
      symptoms particular to the inflamed target tissues. Thus pharmacological doses of
      NAD precursors (nicotinic acid/niacin, nicotinamide/niacinamide, or nicotinamide
      riboside) should be considered as potentially essential to the therapeutic
      success of any IDO-inducing regimen for treating autoimmune diseases. Distinct
      among the NAD precursors, nicotinic acid specifically activates the g-protein
      coupled receptor (GPCR) GPR109a to produce the IDO-inducing tolerogenic
      prostaglandins PGE(2) and PGD(2). Next, PGD(2) is converted to the anti
      inflammatory prostaglandin, 15d-PGJ(2). These prostaglandins exert potent anti
      inflammatory activities through endogenous signaling mechanisms involving the
      GPCRs EP2, EP4, and DP1 along with PPARgamma respectively. Nicotinamide prevents
      type 1 diabetes and ameliorates multiple sclerosis in animal models, while
      nothing is known about the therapeutic potential of nicotinamide riboside.
      Alternatively the direct targeting of the non-redox NAD-dependent proteins using
      resveratrol to activate SIRT1 or PJ34 in order to inhibit PARP1 and prevent
      autoimmune pathogenesis are also given consideration.

PMID- 17430114
TI  - Indoleamine 2,3-dioxygenase in hematopoietic stem cell transplantation.
AB  - Hematopoietic stem cell transplantation (HSCT) is complicated by unwelcome side
      effects that arise on the basis of an altered immune system. Infectious
      complications and alloreactive T-cell responses trigger a process of ongoing
      immune activation and inflammation. Negative-feedback mechanisms to counteract
      inflammation involve the induction of the immunoregulatory enzyme indoleamine 2,3
      dioxygenase (IDO), which mediates anti-inflammatory activities and T-cell
      inhibition via tryptophan catabolism. However, persistent immune activation and
      generalized release of pro-inflammatory cytokines deviate immune regulation
      towards chronic suppression incapable to abrogate the inflammatory response. This
      review focuses on the unique role of tryptophan catabolism in modulating
      inflammatory processes and T-cell responses after HSCT.

PMID- 17430115
TI  - Implications of IFN-gamma-mediated tryptophan catabolism on solid organ
      transplantation.
AB  - The Th1-type cytokine interferon-gamma (IFN-gamma) is known as one of the most
      versatile players of the immune system. In transplantation immunology IFN-gamma
      has been shown to have contradictory effects on allograft survival via effects on
      both, the immune system and on the graft itself. The immunomodulatory enzyme
      indoleamine 2,3-dioxygenase (IDO), widely distributed in mammals, is induced
      preferentially by IFN-gamma. IDO degrades the essential amino acid tryptophan to
      form N-formyl kynurenine which is subsequently converted to niacin. Recently, it
      has been proposed that IFN-gamma-mediated activation of IDO is critically
      involved in the regulation of immune responses, to establish immune-tolerance in
      pregnant mice upon their fetuses, or to induce T-cell unresponsiveness.
      Proliferation of alloreactive T-cells is thereby arrested via local tryptophan
      deprivation and the accumulation of toxic tryptophan catabolites. Despite growing
      recognition of the molecular T-cell regulatory mechanisms, the physiologic role
      of IDO in solid organ transplantation, however, remains unclear. Available
      experimental data indicate that IDO is involved in the mechanism of spontaneous
      donor-specific tolerance of liver grafts, and that genetic manipulation by
      introduction of the IDO gene into allografts is associated with prolonged
      survival. Furthermore, antigen-presenting cells, such as dendritic cells, can
      increase their expression of IDO, thus regulating immune responses. Based on
      these findings, the concept that cells expressing IDO can inhibit T-cell
      responses and hence induce tolerance has emerged as a new paradigm in immunology.
      Here we review the current literature on IDO in the context of transplantation
      and outline its potential implication as a target for tolerance induction.

PMID- 17430116
TI  - IDO and clinical conditions associated with depressive symptoms.
AB  - In the pathogenesis of depressive symptoms the neurotransmitter serotonin plays
      an important role--although the underlining mechanisms are still not clear. The
      synthesis of serotonin is dependent on the availability of tryptophan--an amino
      acid that is linked to the immune system by its catabolism via the enzyme
      indoleamine-2,3-dioxygenase (IDO). Based on this connection research approaches
      addressing different clinical conditions with depressive symptoms and
      immunological involvement have been considered. This review provides an overview
      on the latest research in the field.

PMID- 17430117
TI  - Chronic immune activation underlies morbid obesity: is IDO a key player?
AB  - Morbid obesity is associated with low-grade systemic inflammation and immune
      activation. Thereby various pro-inflammatory cytokines like TNF-alpha, IL-1, IL
      6, IFN-gamma and hormones, such as leptin are synthesized and released in human
      adipose tissue. The immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO) is
      widely distributed in mammals and is inducible preferentially by IFN-gamma. IDO
      degrades the essential amino acid tryptophan to form N-formyl kynurenine which,
      depending on cell type and enzymatic repertoires, is subsequently converted to
      finally form niacin. More recently, it has been proposed that activation of IDO
      is also critically involved in the regulation of immune responses. In obesity
      plasma tryptophan concentrations have been shown to be decreased and to be
      independent of weight reduction or dietary intake. In addition, we previously
      demonstrated that IDO mediated tryptophan catabolism due to chronic immune
      activation is the cause for such reduced tryptophan plasma levels in morbidly
      obese patients compared to lean individuals. Furthermore, these tryptophan
      metabolic changes may subsequently reduce serotonin production and cause mood
      disturbances, depression, and impaired satiety ultimately leading to increased
      caloric uptake and obesity. IDO-mediated tryptophan degradation due to chronic
      immune activation can therefore be considered as the driving force for food
      intake. We here review the potential pathogenic links between chronic immune
      activation and decreased IDO mediated tryptophan and serotonin levels in morbid
      obesity.

PMID- 17430118
TI  - Sepsis.

PMID- 17430120
TI  - Endothelium as a therapeutic target in sepsis.
AB  - The endothelium plays an important role in health and disease. Endothelial
      dysfunction contributes to sepsis pathophysiology. An important goal is to
      develop novel therapies that reverse endothelial dysfunction in sepsis. This
      review will consider the role of the endothelium in sepsis and will highlight its
      untapped therapeutic potential.

PMID- 17430119
TI  - The apoptotic pathway as a therapeutic target in sepsis.
AB  - Recent research has yielded many interesting and potentially important
      therapeutic targets in sepsis. Specifically, the effects of antagonistic anti
      cytokine therapies (tumor necrosis factor-alpha [TNF-alpha], interleukin-1 [IL
      1]) and anti-endotoxin strategies utilizing antibodies against endotoxin or
      endotoxin receptor/carrier molecules (anti-CD14 or anti-LPS-binding protein) have
      been studied. Unfortunately, these approaches often failed clinically, and in
      many cases, the efficacy of these treatments was dependent on the severity of
      sepsis. Recently, clinical trials using insulin to lock blood glucose levels and
      activated protein C treatment have showed that while they provided some survival
      benefit, their efficacy does not appear to be predicated solely upon anti
      inflammatory effects. Here, we will review work done in animal models of
      polymicrobial sepsis and clinical findings that support the hypothesis that
      apoptosis in the immune system is a pathologic event in sepsis that can be a
      therapeutic target. In this respect, experimental studies looking at the septic
      animal suggest that loss of lymphocytes during sepsis may be due to dysregulated
      apoptosis and that this appears to be brought on by a variety of mediators
      effecting 'intrinsic' as well as 'extrinsic' cell death pathways. From a
      therapeutic perspective this has provided a number of novel targets for
      clinically successful current, as well as future therapies, such as caspases
      (caspase inhibition/protease inhibition), pro-apoptotic protein-expression (via
      administration and/or over-expression of Bcl-2) and the death receptor family Fas
      FasL (via. FasFP [fas fusion protein] and the application of siRNA against a
      number pro-apoptotic factors).

PMID- 17430121
TI  - Novel therapies for microvascular permeability in sepsis.
AB  - Sepsis is characterized physiologically by an aberrant systemic inflammatory
      response and microvascular dysfunction. While appropriate antibiotics and
      supportive care are essential in the management of the septic patient, therapies
      targeting specific aspects of the pathophysiology could have a significant impact
      on the morbidity and mortality associated with both sepsis and its sequlea,
      including acute lung injury (ALI). We have characterized several mediators of
      endothelial cell (EC) barrier function that may serve as novel therapies for
      sepsis-induced microvascular dysfunction including simvastatin, adenosine
      triphosphate (ATP), sphingosine 1-phosphate (S1P), and activated protein C (APC).
      Notably, APC is already available for the treatment of severe sepsis, however, to
      date its mechanism of action has been unclear. While distinct in many ways, we
      have found that these agonists have in common the ability to induce dynamic
      rearrangement of the EC actin cytoskeleton that corresponds to barrier
      protection. In addition, we have extended our in vitro findings to relevant
      animal models of endotoxin-induced acute lung injury and have confirmed
      beneficial effects of both simvastatin and S1P which are associated with evidence
      of decreased vascular permeability in this setting. Moreover, our data also
      indicate that APC effects in sepsis may be largely due to augmentation of EC
      barrier function affecting decreased microvascular permeability. We speculate
      that the administration of direct modulators of EC barrier function and
      microvascular permeability, such as those described here, may ultimately become
      the standard of care for the septic patient.

PMID- 17430122
TI  - Ethyl pyruvate: a novel treatment for sepsis.
AB  - Pyruvic acid is a three-carbon alpha-ketocarboxylic acid that plays a central
      role in intermediary metabolism, being the final product of glycolysis and the
      starting substrate for the tricarboxylic acid cycle. Ethyl pyruvate, which is a
      simple aliphatic ester derived from pyruvic acid, has been shown to improve
      survival and ameliorate organ system dysfunction in mice with peritonitis induced
      by cecal ligation and perforation, even when treatment is started as late as 12
      24 hours after the onset of sepsis. In studies using lipopolysaccharide
      stimulated RAW 264.7 murine macrophage-like cells, ethyl pyruvate inhibits
      activation of the pro-inflammatory transcription factor, NF-kappaB, and down
      regulates secretion of a number of pro-inflammatory cytokines, such as TNF. In
      this reductionist in vitro system, ethyl pyruvate also blocks secretion of the
      late-appearing pro-inflammatory cytokine-like molecule, high mobility group B1
      (HMGB1). In murine models of endotoxemia or sepsis, treatment with ethyl pyruvate
      decreases circulating levels of TNF and HMGB1. While the molecular events
      responsible for the salutary effects of ethyl pyruvate remain to be elucidated,
      one mechanism may involve covalent modification of a critical thiol residue in
      the p65 component of NF-kappaB. Ethyl pyruvate warrants evaluation as a
      therapeutic agent for the treatment of sepsis in humans.

PMID- 17430123
TI  - Pathogenesis and sepsis caused by organisms potentially utilized as biologic
      weapons: opportunities for targeted intervention.
AB  - The microorganisms potentially utilized as biologic weapons have a variety of
      pathogenic mechanisms that lead to overwhelming infection, septic shock and
      death. Although many of these organisms have unique pathogenic attributes, the
      development of generic therapies for common pathways would be exceedingly useful
      as countermeasures. This review will examine the features of pathogenesis leading
      to sepsis for key biologic threat agents (causative agents of anthrax, plague,
      tularemia, smallpox and viral hemorrhagic fevers), and highlight current and
      future therapeutic targets. For some of the biologic threat agents, such as
      anthrax, substantial research has yielded a number of targeted sites for
      intervention. For other organisms, further elucidation of the mechanisms of
      pathogenesis and septic shock is needed to direct therapeutic exploration.

PMID- 17430124
TI  - Sepsis and solid organ transplantation.
AB  - Approximately seventy patients undergo solid organ transplantation (SOT) every
      day in the United States. Sepsis remains the first or second most common cause of
      death in transplant recipients, depending on the allograft type. The rapid
      diagnosis and treatment of sepsis is critical to ensure improved survival outcome
      in this special patient population. However, these patients frequently lack the
      classic systemic inflammatory response syndrome (SIRS), commonly seen in the
      immunocompetent patients. In order to minimize delays in the diagnosis of sepsis
      in SOT recipients, it is paramount to recognize the specific risk factors for
      infection associated with each allograft type. In addition, the particular
      surgical techniques involved in each type of transplantation may be closely
      related to the clinical manifestations of the infection process. This correlation
      can further advance the diagnosis and treatment of sepsis. In conclusion,
      precocious diagnosis, rapid initiation of antibiotics, surgical correction when
      necessary, and reduction of immunosuppression, are the mainstream approach to
      sepsis in the SOT patient. The recent developments in severe sepsis are discussed
      in the context of the transplant recipient.

PMID- 17430125
TI  - The cancer related thrombotic tendency in sepsis.
AB  - The host inflammatory response is activated in both cancer and infection. This
      includes enhanced production of acute phase reactants, involvement of coagulation
      and inflammation and the potential for systemic effects. This overview will
      identify the prothrombotic links between cancer and sepsis and suggest
      antithrombotic agents as an approach in the specific treatment of sepsis in
      cancer patients.

PMID- 17430126
TI  - The effect of statins on postprandial lipemia.
AB  - Several studies showed that postprandial plasma triglyceride (TG) concentrations
      are higher in patients with coronary heart disease. TG-rich lipoprotein remnants
      accumulated in the postprandial state are involved in atherogenesis and in events
      leading to thrombosis. Lipid lowering drugs, such as 3-hydroxy-3-methylglutaryl
      CoA reductase inhibitors (statins) are of significant benefit in the primary and
      secondary prevention of atherosclerosis. Statins can decrease total cholesterol
      and low density lipoprotein cholesterol as well as TG concentrations and improve
      postprandial lipoprotein metabolism. Since abnormal postprandial lipemia is
      associated with pathological conditions, its treatment is relevant. This review
      considers the effect of statins on postprandial lipemia.

PMID- 17430127
TI  - Lipid management and peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is a common disorder usually associated with
      silent or symptomatic arterial disease elsewhere in the circulation and a
      "cluster" of cardiovascular risk factors (e.g. smoking, dyslipidemia,
      hypertension, and insulin resistance/diabetes mellitus). The medical management
      of PAD should focus on both the relief of symptoms and prevention of secondary
      cardiovascular complications. This approach must include smoking cessation,
      optimal cholesterol levels, blood pressure and glycemic control as well as
      prescribing antiplatelet therapy. This review focuses on the evidence supporting
      the use of lipid-lowering drugs in PAD. Several trials indicate that getting low
      density lipoprotein-cholesterol levels to target (<2.6 mmol/l; 100 mg/dl), or
      even lower, is associated with improvement of symptoms and a reduction in
      vascular events in patients with PAD.

PMID- 17430129
TI  - Heme oxygenase -1 gene therapy: recent advances and therapeutic applications.
AB  - Heme oxygenase-1 (HO-1) is regarded as a sensitive and reliable indicator of
      cellular oxidative stress. Studies on carbon monoxide (CO) and bilirubin, two of
      the three (iron is the third) end products of heme degradation have improved the
      understanding of the protective role of HO against oxidative injury. CO is a
      vasoactive molecule and bilirubin is an antioxidant, and an increase in their
      production through an increase in HO activity assists other antioxidant systems
      in attenuating the overall production of reactive oxygen species (ROS), thus
      facilitating cellular resistance to oxidative injury. Gene transfer is used to
      insert specific genes into cells that are either otherwise deficient in or that
      underexpress the gene. Successful HO gene transfer requires two essential
      elements to produce functional HO activity. Firstly, the HO gene must be
      delivered in a safe vector, e.g., adenoviral, retroviral or leptosome based
      vectors, currently being used in clinical trials. Secondly, with the exception of
      HO gene delivery to either ocular or cardiovascular tissue via catheter-based
      delivery systems, HO delivery must be site and organ specific. This has been
      achieved in rabbit ocular tissues, rat liver, kidney and vasculature, SHR kidney,
      and endothelial cells [Abraham et al., 1995a; Abraham et al., 1995b; Abraham et
      al., 2002c; Quan et al., 2004; Sabaawy et al., 2000; Sabaawy et al., 2001; Yang
      et al., 2004]. In this review, we discuss the functional significance of the HO
      system in various pathophysiological conditions and the beneficial therapeutic
      applications of human HO gene transfer and gene therapy in a variety of clinical
      circumstances.

PMID- 17430128
TI  - Gene therapy for type I glycogen storage diseases.
AB  - The type I glycogen storage diseases (GSD-I) are a group of related diseases
      caused by a deficiency in the glucose-6-phosphatase-alpha (G6Pase-alpha) system,
      a key enzyme complex that is essential for the maintenance of blood glucose
      homeostasis between meals. The complex consists of a glucose-6-phosphate
      transporter (G6PT) that translocates glucose-6-phosphate from the cytoplasm into
      the lumen of the endoplasmic reticulum, and a G6Pase-alpha catalytic unit that
      hydrolyses the glucose-6-phosphate into glucose and phosphate. A deficiency in
      G6Pase-alpha causes GSD type Ia (GSD-Ia) and a deficiency in G6PT causes GSD type
      Ib (GSD-Ib). Both GSD-Ia and GSD-Ib patients manifest a disturbed glucose
      homeostasis, while GSD-Ib patients also suffer symptoms of neutropenia and
      myeloid dysfunctions. G6Pase-alpha and G6PT are both hydrophobic endoplasmic
      reticulum-associated transmembrane proteins that can not expressed in soluble
      active forms. Therefore protein replacement therapy of GSD-I is not an option.
      Animal models of GSD-Ia and GSD-Ib that mimic the human disorders are available.
      Both adenovirus- and adeno-associated virus (AAV)-mediated gene therapies have
      been evaluated for GSD-Ia in these model systems. While adenoviral therapy
      produces only short term corrections and only impacts liver expression of the
      gene, AAV-mediated therapy delivers the transgene to both the liver and kidney,
      achieving longer term correction of the GSD-Ia disorder, although there are
      substantial differences in efficacy depending on the AAV serotype used. Gene
      therapy for GSD-Ib in the animal model is still in its infancy, although an
      adenoviral construct has improved the metabolic profile and myeloid function.
      Taken together further refinements in gene therapy may hold long term benefits
      for the treatment of type I GSD disorders.

PMID- 17430130
TI  - Restoration of the striatal dopamine synthesis for Parkinson's disease: viral
      vector-mediated enzyme replacement strategy.
AB  - Parkinson's disease is the second most common neurodegenerative disease. It is
      charaterized by a progressive loss of dopamine (DA) producing neurons in the
      midbrain, which result in a decline of DA innervations present in the forebrain,
      in particular, the striatum. The disease leads to appearance of motor symptoms
      involving akinesia/bradykinesia, gait disturbances, postural imbalance and
      tremor. Oral administration of L-3,4-dihydroxyphenylalanine (L-DOPA), the
      precursor of DA, provides very good symptomatic relief, but this intermittent and
      pharmacological treatment is compromised by severe side effects, such as the
      appearance of abnormal involuntary movements. Viral vector-mediated direct gene
      transfer techniques are currently being explored in order to provide continuous
      and stable synthesis of DA in the brain. This review focuses on the basic idea of
      DA replacement, first describing the enzymatic machinery important for DA
      synthesis and secondly the various alternative strategies pursued in several
      laboratories. The DOPA delivery strategy, based on the co-transduction of
      tyrosine hydroxylase (TH), and GTP cyclohydrolase 1 (GCH1) genes, has been shown
      to be a powerful approach providing a robust behavioral recovery and reversal of
      side effects of the pulsatile administration of L-DOPA medication. The DA
      delivery strategy, on the other hand, aims at triple transduction of the TH, GCH1
      and aromatic amino-acid decarboxylase (AADC) enzymes, and thereby provide a
      higher rate of conversion of DOPA to DA. Finally, transduction of AADC alone has
      been proposed as a means to improve the conversion of peripherally administered L
      DOPA. As the basic scientific rationale behind these strategies are well
      understood and the results of the animal experiments are very encouraging, we are
      now entering into an exciting phase with increasing momentum toward the first
      clinical applications using this experimental therapy in patients suffering from
      PD.

PMID- 17430131
TI  - Retinal degenerations: from cell signaling to cell therapy; pre-clinical and
      clinical issues.
AB  - Extracellular signaling molecules have been implicated in the progression of
      Retinal Degeneration (RD). Gene regulatory events linked to the maintenance of
      retinal structure and function incorporate signaling cascades that may serve as
      therapeutic targets for some forms of blindness. This review shall focus on the
      evidence for non-cell-autonomous mechanisms that affect the pattern of
      degeneration seen in retinal dystrophies, the types of signals that may influence
      the course of degeneration and finally with the related prospects for retinal
      therapies.

PMID- 17430132
TI  - Gene and stem cell therapy in the treatment of erectile dysfunction and pulmonary
      hypertension; potential treatments for the common problem of endothelial
      dysfunction.
AB  - The endothelium has an important regulatory role in the maintenance of vascular
      homeostasis, vascular tone, blood flow, and in preserving a non-thrombogenic
      blood-tissue interface. Injury to the vascular wall with subsequent endothelial
      dysfunction alters these important regulatory functions leading to a state of
      abnormal endothelial function. In this paper, we review the pathophysiology of
      endothelial dysfunction and how this disorder is common to the development of
      erectile dysfunction and of pulmonary arterial hypertension. Current medical
      therapies for these two disorders are discussed followed by a review of the
      preclinical studies involving currently available strategies for gene and stem
      cell therapy and their potential for the clinical treatment of these two
      disorders of endothelial dysfunction.

PMID- 17430133
TI  - Sclerosing polidocanol injections of small vessels to treat the chronic painful
      tendon.
AB  - The chronic painful tendon (tendinopathy, tendinosis) is generally considered
      difficult to treat, not seldom causing long-term disability and sometimes ending
      the sports or work carreer. Most common sites for tendinopathy are the Achilles-,
      patellar-, extensor carpi radialis brevis (ERCB)-, and supraspinatus tendons. The
      origin of pain has for many years been unknown, but recently, by using ultrasound
      (US) + colour Doppler (CD), immunohistochemical analyses of tendon biopsies, and
      diagnostic injections of local anaestesia, we found a close relationship between
      areas with vasculo-neural ingrowth and tendon pain. Sensory nerves (Substance-P
      SP and Calcitonin Gene Related Peptide-CGRP) were found inside and outside the
      vascular wall. In following clinical studies we have demonstrated good short-and
      mid-term clinical results using treatment with US+CD-guided sclerosing
      polidocanol injections, targeting the area with neovessels outside the tendon.
      Two-year follow ups have showed remaining good clinical results, and
      sonographically signs of remodelling with a significantly thinner tendon with a
      more normal structure. Whether the effects of polidocanol are mediated through
      destruction of neovessels, activity on nerves or a combination, is under
      evaluation.

PMID- 17430134
TI  - Relaxin as a cardiovascular hormone: physiology, pathophysiology and therapeutic
      promises.
AB  - Relaxin is a hormone belonging to the so-called relaxin superfamily, which also
      includes insulin-like peptides. Relaxin is best known for its effects on the
      female reproductive system, which primarily include lengthening of the pubic
      symphysis and softening of the tissues of the birth canal, stimulating mammary
      and endometrial development, and maintenance of myometrial quiescence. In recent
      years, evidence has been accumulating that relaxin can have multiple and diverse
      effects on both reproductive and nonreproductive organs, tissues and cells, thus
      acting as a sort of 'manager' hormone to optimize the many physiological changes
      taking place during pregnancy. Among the specific relaxin targets, there are the
      blood vessels and the heart. In fact, relaxin is a potent vasodilatator of the
      systemic and coronary circulation, by a mechanism of action involving nitric
      oxide, and can influence cardiac beating rate. Identification of the numerous
      possible roles of relaxin in the pathophysiology of cardiovascular diseases, not
      to mention the possible therapeutical applications of relaxin, remains a
      difficult task. Based on the known biological effects of relaxin, it is becoming
      increasingly evident that the potential fields of clinical investigation of human
      relaxin as a cardiovascular drug could be in ischemic heart disease (acute and
      chronic myocardial infarction), in cardiac fibrosis, in cell transplantation for
      cardiac repair, and in obliterative peripheral arterial disease. Availability of
      the homologous human peptide, knowledge of its pharmacological, pharmacokinetic
      and pharmacodynamic profiles, and increasing interest of clinicians and
      pharmaceutical companies should synergistically act to transfer relaxin from the
      laboratory bench to the bedside.

PMID- 17430135
TI  - Integrins: novel therapeutic targets for cardiovascular diseases.
AB  - Integrins are the principle mediators of molecular dialog between a cell and its
      extracellular matrix environment. The unique combinations of integrin subunits
      determine which extracellular matrix molecules are recognized by a cell. Recent
      studies have demonstrated that remodeling in heart and vasculature is linked to
      alterations in extracellular matrix and integrin expression. The roles of
      integrins in controlling cellular behavior have made these molecules highly
      attractive drug targets. New insights into mechanisms whereby the extracellular
      matrix takes part in the control of smooth muscle cell proliferation and cardiac
      growth suggest a number of putative targets for future therapies that can be
      applied to increase plaque stability, prevent the clinical consequences of
      atherosclerosis and improve outcomes after interventional procedures such as
      cardiac transplantation. Therapeutic candidates include antibodies, cyclic
      peptides, peptidomimetics and small molecules. The integrin inhibitors Integrilin
      and ReoPro have been approved as blood thinners in cardiovascular disease, and
      newer agents are undergoing testing. Although integrin function is important in
      the cardiovascular system, there are wide gaps in knowledge. In this review, we
      discuss the primary mechanisms of action and signaling of integrins in the
      cardiac and vascular system in normal and pathological states, as well as
      therapeutic strategies for targeting these molecules in the cardiovascular
      system.

PMID- 17430136
TI  - Emerging therapeutic approaches multi-targeting receptor tyrosine kinases and g
      protein-coupled receptors in cardiovascular disease.
AB  - Advances in molecular biology and functional genomics have demonstrated that the
      "one gene-one phenotype-one drug" paradigm, that has dominated pharmaceutical
      industry and clinical pharmacology thinking, is too simplistic for management of
      complex polygenic traits. The traditional highly specific drugs with unique
      target have proven their clinical usefulness. However, they do not always display
      the required efficacy versus side-effect profile, in major part because polygenic
      traits are determined by redundant mechanisms. Simultaneously modulating multiple
      targets may enhance therapeutic efficacy in the treatment of a range of
      disorders. Multi-targeting can be achieved by the combination of different drugs
      having specific single target activity. This approach introduces potential
      problems with pharmacokinetic interactions, toxicity and patient compliance. High
      efficacy can be achieved, alternatively, by administering selectively non
      selective drugs with complex pharmacological profiles directed towards various
      molecular targets and affording pleiotropic actions. Dual- or multiple-ligands
      can be discovered accidentally, but can also be rationally designed according to
      validated medicinal chemical approaches. The merits of multiple-target versus
      single-target approaches for cardiovascular disease traits are assessed in the
      present review. The main aim is to make evident the molecular biological basis of
      the possibility for targeting multiple sites and the subsequently emerging
      strategies for interventions with superior clinical value by harnessing receptor
      tyrosine kinases (RTKs) such as VEGFR, PDGFR, bFGFR, as well as G protein-coupled
      receptors (GPCRs). The premises for lead discovery in this new area and the
      challenges of medicinal chemistry behind the rational design of multitasked
      ligands are also discussed.

PMID- 17430137
TI  - Current and emerging concepts in the management of neovascular age-related
      macular degeneration.
AB  - Age-related macular degeneration (AMD) is the leading cause of blindness in the
      elderly worldwide. The more severe form of the disease, known as neovascular AMD,
      is characterized by aberrant growth of blood vessels from the choroid into the
      subretinal space. This pathologic choroidal neovascularization can have drastic
      consequences, often seriously impairing vision in affected individuals. Current
      treatment approaches focus on combination therapies that include photodynamic
      therapy in conjunction with numerous forms of antiangiogenic or anti-inflammatory
      drug intervention. To date, however, no adequate treatment is available for the
      majority of affected individuals. The threat of a rapidly aging population
      provides the impetus for aggressive efforts to control the prevalence and
      progression of this disease. This review will outline the currently available
      pharmacotherapies, discussing the justification for their use as well as their
      shortcomings. Furthermore, drugs that are currently under investigation as
      monotherapies and adjuncts will be highlighted. The potential for alternate
      targets will also be examined, with a focus on the most promising candidates.

PMID- 17430138
TI  - Nitric oxide, malnutrition and chronic renal failure.
AB  - The conditionally essential amino acid L-arginine is the substrate for nitric
      oxide (NO) synthesis, a key second messenger involved in physiological functions
      including endothelium-dependent vascular relaxation and inhibition of platelet
      adhesion and aggregation. Extracellular L-arginine transport seems to be
      essential for the production of NO by the action of NO synthases (NOS), even when
      the intracellular levels of L-arginine are available in excess (L-arginine
      paradox). Chronic renal failure (CRF) is a complex clinical condition associated
      with accelerated atherosclerosis and thrombosis leading to cardiovascular events.
      Various studies document that markers of malnutrition and inflammation, such as
      low body mass index (BMI), C-reactive protein (CRP) and interleukin-6 (IL-6), are
      strong independent predictors of cardiovascular mortality in patients with end
      stage renal disease (ESRD). There is considerable literature demonstrating that a
      disturbance in the nitric oxide control mechanism plays a role in mediating the
      haemodynamic and haemostatic disorders present in CRF. Endogenous analogues of L
      arginine, ADMA and L-NMMA, which can inhibit NO synthesis and L-arginine
      transport, are increased whilst L-arginine is reduced in plasma from all stages
      of CRF patients. In this context, the uptake of L-arginine in blood cells is
      increased in undialysed CRF patients and in patients treated by CAPD and
      haemodialysis. In platelets obtained from haemodialysis patients, the activation
      of L-arginine transport and NO production was limited to well-nourished patients.
      Impairment in nitric oxide bioactivity, coupled with malnutrition and
      inflammation, may contribute to increased incidence of atherothrombotic events in
      CRF. This article summarizes the current knowledge of L-arginine-nitric oxide
      pathway and malnutrition in CRF and briefly describes possible therapeutic
      interventions.

PMID- 17430139
TI  - Molecular genetics of quantitative fibrinogen disorders.
AB  - Fibrinogen is a complex glycoprotein involved in the final step of the
      coagulation cascade as the precursor of fibrin monomers that participate in the
      formation of the haemostatic plug. Three genes (FGA, FGB, and FGG) clustered on
      chromosome 4q31.3-4q32.1 encode the three polypeptide chains (Aalpha, Bbeta, and
      gamma), which in a pairwise fashion form the hexameric circulating molecule.
      Among congenital fibrinogen deficiencies, quantitative defects (also called type
      I deficiencies; i.e. congenital afibrino-genemia [CAF] and hypofibrinogenemia)
      are characterized by the concomitant absence or reduction of coagulant activity
      and immunoreactive protein, while qualitative defects (type II deficiencies; i.e.
      dysfibrinogenemia and hypodysfibrino-genemia) show low clotting protein in
      contrast with normal or moderately reduced antigen. Patients affected by CAF
      (Mendelian Inheritance in Man, [MIM] #202400) or severe hypofibrinogenemia
      (MIM+134820, *134830, and *134850) may experience bleeding manifestations varying
      from mild to catastrophic. Although many cases of fibrinogen deficiencies have
      been described from a clinical point of view, only in a minority of cases the
      causal mutation was identified. The genetic defects so far described, most unique
      for any analyzed family, are invariantly located in the fibrinogen cluster; for
      only few of them the pathogenic role either at the protein or at the mRNA level
      has been investigated. This review, besides providing a concise description of
      the main structural and functional properties of fibrinogen and giving an
      overview of the clinical manifestations, the laboratory diagnosis and therapeutic
      approches, will be focused on the present knowledge on the genetic basis of
      quantitative fibrinogen deficiencies. Our systematic analysis of the available
      clinical and genetic data on these disorders evidences their high allelic
      heterogeneity, the existence of different pathogenic mechanisms, and the absence
      of strong genotype/phenotype correlations.

PMID- 17430140
TI  - The efficacy of viral capsid inhibitors in human enterovirus infection and
      associated diseases.
AB  - Enteroviruses are members of picornavirus family which causes diverse and severe
      diseases in humans and animals. Clinical manifestations of enterovirus infections
      include fever, hand, foot, and mouth disease, and herpangina. Enteroviruses also
      cause potentially severe and life-threatening infections such as meningitis,
      encephalitis, myocarditis, polio-like syndrome, and neonatal sepsis. With the
      emergence of enterovirus all over the world as the major causative agent of HFMD
      fatalities in recent years and in the absence of any effective anti-enteroviral
      therapy, there is clearly a need to find a specific antiviral therapy. Steps such
      as viral attachment, uncoating, viral RNA replication, and protein synthesis in
      the replication cycle can serve as potential targets for antiviral agents. Agents
      targeted at viral protein 1 (VP1), a relatively conserved capsid structure
      mediating viral adsorption and uncoating process, is of great potential to be
      anti-enterovirus drugs. Recently, considerable efforts have been made in the
      development of antiviral compounds targeting the capsid protein of enterovirus.
      This review summarizes the development of small molecules targeting enteroviral
      capsid protein as effective antiviral therapy.

PMID- 17430141
TI  - Iron, oxidative stress and early neurological deterioration in ischemic stroke.
AB  - Ischemic stroke is characterized by the disruption of cerebral blood flow, which
      produces a central core of dead neurons surrounded by a penumbra of damaged but
      partially functional neurons. Many factors are associated with such brain injury,
      including excitotoxicity and free radicals. Recent clinical studies have shown
      that high plasma ferritin levels are detrimental in acute ischemic stroke. As an
      iron-storage protein, ferritin can act both as a scavenger and as a donor of free
      iron, which is a source of hydroxyl radicals. Following disruption of the blood
      brain barrier, the ferritin and the free iron that have accumulated in
      endothelial cells in brain capillaries, together with plasma ferritin, can enter
      the penumbra. Iron-dependent oxidative stress in the penumbra can lead to
      necrosis and further neurological deterioration following ischemic stroke. An
      excess of iron should be considered pathological in the ischemic brain.
      Therapeutic strategies for ischemic stroke should attempt to restore brain
      function within the penumbra. Consequently, the iron content of systemic stores
      should be measured, and anti-oxidant treatment should be considered when it is
      excessive.

PMID- 17430142
TI  - Genomic and proteomic screening of apoptosis mitochondrial regulators for drug
      target discovery.
AB  - Screening strategies of therapeutic molecules and targets have received
      increasing attention during the past few years. Indeed, identification of novel
      compounds and drug targets involved in apoptosis control is a major rate-limiting
      step in anticancer drug development efforts. In this review, we discuss the
      current screening methodologies to discover novel potential therapeutics targets
      and drugs implicated in the apoptotic pathway, in particular the intrinsic
      pathway. In addition, we present a proteomic screening strategy that led us to
      identify a mitochondrial glutathione-S-transferase as a novel regulator of the
      pro-apoptotic adenine nucleotide translocase pore function.

PMID- 17430143
TI  - Helicases as antiviral and anticancer drug targets.
AB  - In the cell, the unwinding of double-stranded polynucleotides is catalyzed by
      helicases that are present in all kingdoms of life from virus to man. Viruses,
      like all other organisms, synthesize their DNA or RNA genomes in a template
      dependent manner. In addition to DNA or RNA polymerases, a helicase is therefore
      required to displace the single-stranded genome after replication, thus leading
      to the formation of progeny viral particles. In drug design against viral
      helicases, a number of viral helicase inhibitors have been developed and used in
      clinical studies. In humans, DNA helicases play essential roles in facilitating
      cellular DNA metabolisms including genome replication, DNA repair, recombination,
      transcription as well as telomere maintenance. The care-taker roles of helicases
      suggest that they might be suitable for targeting to prevent cell proliferation
      during carcinogenesis. Identifying helicase specific-inhibitors may lead to the
      development of drugs in the treatment of human cancers. In addition, some
      helicases such as BLM and WRN interact physically and functionally with
      telomerases and are involved in telomere maintenance. Hence, an antitumor therapy
      designed to interfere with both helicases and telomerases may be much more
      effective than the helicase or telomerase inhibitors alone. This review addresses
      these topics and discusses the design of antiviral and antitumoral agents based
      on the knowledge of structures and functions of helicases.

PMID- 17430144
TI  - The role of the cannabinoid CB2 receptor in pain transmission and therapeutic
      potential of small molecule CB2 receptor agonists.
AB  - This review gives a brief overview of the expression patterns, molecular
      pharmacology and physiological role of the cannabinoid 2 receptor (CB2) in pain.
      Particular emphasis is given to the therapeutic utility of CB2 receptor agonists.
      Through studies utilizing selective CB2 receptor agonists, non-selective
      cannabinoid agonists in conjunction with selective CB1 and CB2 receptor
      antagonists, or CB2 receptor knockout mice, it is now clear that this receptor
      plays a critical role in nociception. To this end, CB2 receptors have been shown
      to modulate acute pain, chronic inflammatory pain, post-surgical pain, cancer
      pain and pain associated with nerve injury. Here we review these studies and the
      compounds that were utilized. We hypothesize the mechanism of action by which the
      CB2 receptor could be involved in these processes. Finally we summarize the most
      recent novel chemical scaffolds that are being investigated towards advancing
      selective CB2 receptor agonists into the clinic. Many new pharmacological agents
      have been identified by high throughput screening and small molecule lead
      discovery and optimization in the past 10 years. It is anticipated that at least
      some of these agents may ultimately constitute effective new pain therapeutics
      that lack the side effects associated with traditional cannabinoid ligands.

PMID- 17430145
TI  - Implantable electrochemical sensors for biomedical and clinical applications:
      progress, problems, and future possibilities.
AB  - Biosensors are of great interest for their ability to monitor clinically
      important analytes such as blood gases, electrolytes, and metabolites. A classic
      example is to monitor the dynamics of blood-glucose levels for treating diabetes.
      However, the current practice, based on a three decade old technology, requires a
      drop of blood on a test strip, which is in dire need of replacement. The
      increasing demands and interests in developing implantable glucose sensors for
      treating diabetes has led to notable progress in this area, and various
      electrochemical sensors have been developed for intravascular and subcutaneous
      applications. However, implantations are plagued by biofouling, tissue
      destruction and infection around the implanted sensors and the response signals
      must be interpreted in terms of blood or plasma concentrations for clinical
      utility, rather than tissue fluid levels. This review focuses on the potentials
      and pitfalls of implantable electrochemical sensors and presents our opinions
      about future possibilities of such implantable devices with respect to
      biocompatibility issues, long-term calibration, and other aging effects on the
      sensors.

PMID- 17430146
TI  - Depression.

PMID- 17430147
TI  - Metabotropic glutamate receptors in the control of mood disorders.
AB  - Current treatments for depression are less than optimal in terms of onset of
      action, response and remission rates, and side-effect profiles. Glutamate is the
      major excitatory neurotransmitter controlling synaptic excitability and
      plasticity in most brain circuits, including limbic pathways involved in
      depression. Thus, drugs that target glutamate neuronal transmission offer novel
      approaches to treat depression. Recently, the NMDA receptor antagonist ketamine
      has demonstrated clinical efficacy in a randomized clinical trial of depressed
      patients. Metabotropic glutamate (mGlu) receptors function to regulate glutamate
      neuronal transmission by altering the release of neurotransmitter or modulating
      the post-synaptic responses to glutamate. Accumulating evidence from biochemical
      and behavioral studies support the idea that the regulation of glutamatergic
      neurotransmission via mGlu receptors is linked to mood disorders and that these
      receptors may serve as novel targets for the discovery of small molecule
      modulators with unique antidepressant properties. For example, mGlu receptor
      modulation can facilitate neuronal stem cell proliferation (neurogenesis) and the
      release of neurotransmitters that are associated with treatment response to
      depression in humans (serotonin, norepinephrine, dopamine). In particular,
      compounds that antagonize mGlu2, mGlu3 and/or mGlu5 receptors (e.g. LY341495,
      MSG0039, MPEP) have been linked to the above pharmacology and have also shown in
      vivo activity in animal models predictive of antidepressant efficacy such as the
      forced-swim test. The in vivo actions of these agents can be antagonized by
      compounds that block AMPA receptors, suggesting that their actions are direct
      downstream consequences of the enhancement of glutamate neuronal transmission in
      brain regions involved in depression. These data provide new approaches to
      finding mechanistically distinct drugs for depression that may have advantages
      over current therapies for some patients. Moreover, since the mood disorders
      encompase a non-homogenous set of symptoms, comorbid disorders, and potential
      etiologies, the rich arsensel that exists within the mGlu receptor families
      provides an opportunity for both broad and customized therapeutics.

PMID- 17430148
TI  - The NMDA receptor as a therapeutic target in major depressive disorder.
AB  - Ample evidence indicates that glutamate homeostasis and neurotransmission are
      disrupted in major depressive disorder; but the nature of this disruption and the
      mechanisms by which it contributes to the syndrome are unclear. Likewise, the
      effect of existing antidepressants on glutamate is unclear, as is the potential
      of drugs directly targeting glutamatergic neurotransmission to act as novel
      antidepressant medications. These are areas of active research. Here we review
      current knowledge of the contribution of the NMDA receptor, one of the several
      types of glutamate receptor, to depression and its treatment. Several lines of
      evidence, in humans and in animal models, support the contention that
      neurotransmission via the NMDA receptor is dysregulated in depression. Drugs that
      target the NMDA receptor have shown antidepressant properties in both clinical
      and preclinical studies. Nevertheless, other effects of such medications,
      including both cognitive side effects and their psychotomimetic properties,
      complicate such an application and represent a challenge to the development of
      clinically useful agents.

PMID- 17430149
TI  - AMPA receptors in the therapeutic management of depression.
AB  - There is an increasing body of evidence implicating a role for alpha-amino-3
      hydroxy-5-methyl-4 isoxazoleproprionic acid (AMPA) receptors in major depression
      and in the actions of antidepressant drugs. Alterations in AMPA receptors and
      other ionotropic glutamate receptors have been reported in depression, and
      following antidepressant treatment. Compounds which augment signaling through
      AMPA receptors (AMPA receptor potentiators) exhibit antidepressant-like
      behavioral effects in animal models, and produce neuronal effects similar to
      those produced by currently available antidepressants, including neurotrophin
      induction and increases in hippocampal progenitor cell proliferation.
      Additionally, the antidepressant fluoxetine has been found to alter AMPA receptor
      phosphorylation in a manner that is expected to increase AMPA receptor signaling.
      Data from mutant mice suggest that AMPA receptors may regulate the expression of
      brain-derived neurotrophic factor, a neurotrophin which has been implicated in
      the actions of antidepressant therapies. Combined, these data suggest that AMPA
      receptors may be in a key position to regulate mood disorders, and that compounds
      which target AMPA receptors may prove useful in the clinical management of
      depression.

PMID- 17430150
TI  - GABAergic contributions to the pathophysiology of depression and the mechanism of
      antidepressant action.
AB  - Increasing evidence suggests that abnormalities in amino neurotransmission are
      associated with the neurobiology of depression. Preclinical studies demonstrate
      that GABA modulating agents are active in commonly used rodent behavioral models
      of antidepressant activity, and that chronic administration of antidepressant
      drugs induces marked changes in GABAergic function. In humans, depressed patients
      have lower plasma, CSF and brain GABA concentrations than non-depressed
      comparison subjects. The recent discovery that several anticonvulsant and GABA
      mimetic agents possess mood stabilizing and antidepressant properties has further
      increased interest in these findings. This review outlines the existing
      literature investigating the possible involvement of GABA in the neurobiology of
      depression and briefly highlights how this information may afford new targets for
      antidepressant drug development.

PMID- 17430151
TI  - Triple reuptake inhibitors ("broad spectrum" antidepressants).
AB  - The majority of antidepressants in current use inhibit the uptake of serotonin
      and/or norepinephrine. Drugs inhibiting the uptake of serotonin, norepinephrine
      and dopamine (triple reuptake inhibitors) may offer therapeutic advantages
      compared to single and/or dual reuptake inhibitors. This review provides a
      rationale for developing this class of compound and describes the results of
      preclinical and clinical studies with a family of triple reuptake inhibitors.

PMID- 17430152
TI  - Targeting neurotrophic/growth factor expression and signaling for antidepressant
      drug development.
AB  - Preclinical and clinical studies have demonstrated that stress and depression
      result in cell atrophy and loss in limbic and cortical brain regions while
      antidepressants reverse these effects. In concert with these findings, reduced
      expression of numerous genes that mediate neurotrophin and growth factor
      signaling has been observed in depressed patients and in stressed animals.
      Further, antidepressants are known to elevate the expression of multiple genes
      involved in these signaling pathways. Together, these findings have implicated
      neurotrophic factors in both the etiology and treatment of depression. Below we
      review the current data supporting the neurotrophic hypothesis of depression, and
      discuss potential approaches to pharmacologically upregulate neurotrophic/growth
      factor signaling to elicit antidepressant responses.

PMID- 17430154
TI  - Drug resistance in childhood acute myeloid leukemia.
AB  - Therapy results in childhood AML differ from those of ALL. The development of
      drug resistance is the limiting factor in the therapy of AML. Different problems
      of drug resistance in childhood AML, with emphasis to age and in comparison to
      adult AML are presented. In vitro and in vivo aspects are discussed, together
      with mechanisms of resistance to cytostatic drugs, focused on clinical relevance
      of cellular drug resistance profile and its prognostic value. Possibilities of
      modulation and circumvention of drug resistance are reviewed, with stress on new
      drugs being tested. Taking into account both children and adults, it seems that
      age is adversely related to therapy outcome in AML, and the percentage of
      patients with favorable cytogenetics decreases with age; however, age is
      positively correlated with multi-drug resistance and the proportion of patients
      with unfavorable cytogenetics. AML is considered a stem cell disease. BCRP, PGP
      and MRP's are preferentially expressed in leukemic stem cells, making this
      disease drug resistant. Cellular drug resistance in AML cells seems to be similar
      throughout all other age groups, however the higher the age, the worse the
      outcome. In childhood AML, no drug is more effective in comparison to ALL, and
      cellular drug resistance is partially related to chromosomal abnormalities.
      Pediatric AML is equally resistant as adult AML. Pediatric and adult AML,
      respectively, are possibly equally drug resistant on initial diagnosis and at
      relapse. In contrast to ALL, the prognostic value of in vitro drug resistance in
      childhood AML has not been well documented yet.

PMID- 17430155
TI  - Drug resistance and methylation in myelodysplastic syndrome.
AB  - Myelodysplastic syndrome is a clonal hematopoietic stem cell disorder that
      presents a poor survival for patients treated with standard therapies other than
      stem-cell transplantation. Multi-drug resistance (MDR) to simultaneous drugs used
      in chemotherapy is a major concern in the treatment of cancer and also in MDS.
      ATP-binding cassette (ABC) transporters are involved in the main mechanism that
      confers drug resistance to cells. Increased expression of drug resistance genes,
      such as MDR1, MRP1 and LRP, is involved with multi-drug resistance in MDS. The
      expression of these drug efflux transporters acts in synergy with other
      alterations, such as epigenetic events, increases in multidrug resistance in MDS.
      Methylation, the main epigenetic mechanism is widely explored in other
      hematological malignancies; however, in MDS, this mechanism is poorly
      investigated. Clinical trials evaluated or are under ongoing evaluation of drugs
      that abrogated ABC transporters action or reversed the abnormal methylation of
      some genes in MDS. In this report, we explore the data available in the field of
      drug resistance and methylation both in pediatric and adult MDS.

PMID- 17430156
TI  - Classification of sarcomas using bioinformatics and molecular profiling.
AB  - Recent advances in genomic and proteomic technologies have revolutionized our way
      of classifying cancers. These high-throughput technologies allow the use of
      powerful and multivariate bioinformatic approaches to develop molecular
      classifiers. These classifiers can then be used to distinguish different types of
      tumors based on their molecular profiles. This is particularly important for
      heterogeneous groups of tumors such as sarcomas. Although sarcomas have a variety
      of histological appearances, the distinction among some of the diagnostic groups
      is vague. Therefore, molecular classification provides a new way to distinguish
      histologically similar but molecularly different types of sarcomas, and hence
      improves tumor diagnosis and stratification. In addition, identification of
      discriminatory genes that carry information to differentiate clinical subtypes of
      sarcomas will further elucidate the underlying molecular pathways and
      pathological mechanisms of these tumors. In this article, we review some current
      methods used in genomic and proteomic profiling, outline the approach of using
      bioinformatic techniques to develop a molecular classifier, and discuss some
      recent examples to illustrate the use of molecular classification to distinguish
      different types of sarcomas and understand the biology of these tumors.

PMID- 17430157
TI  - Drug resistance in hepatoblastoma.
AB  - Treatment results of human hepatoblastoma (HB) have been improved remarkably
      during recent years, mainly through the establishment of integrated regimens
      controlled and coordinated by multicentric treatment studies. Today, neoadjuvant
      and adjuvant chemotherapy is combined with surgical resection of the tumors. The
      main therapeutic goal is a complete surgical removal of tumor masses, which is
      also essential for the survival of the patients. Despite improved overall
      survival rates, treatment results of advanced tumors are still far from being
      satisfying. Multidrug resistance has been identified as a major factor
      responsible for the bad prognosis of children suffering from advanced staged
      hepatoblastoma. During recent years investigations focused on factors
      contributing to drug resistance in hepatoblastoma and on possible approaches
      towards overcoming this therapeutical challenge. Alternative approaches that are
      currently evaluated in experimental and clinical settings comprise new cytotoxic
      agents, chemosensitizers, gene directed applications but also surgical techniques
      and an expansion of indication for liver transplantation.

PMID- 17430158
TI  - Drug resistance in renal tumors of childhood.
AB  - Renal cancers are as one of the most common drug resistant neoplasms affecting
      children and multidrug resistance (MDR) happened to be an important reason for
      the failure of chemotherapy in refractory cancers of childhood. MDR can be
      intrinsic or acquired, depending on the time of its occurrence, either at
      diagnosis or during chemotherapy. Renal cancers often have intrinsic form of MDR
      because of de novo expression of P-glycoprotein (P-gp) in renal cells. Molecular
      investigations on MDR during the past two decades have led to the isolation and
      characterization of genes coding for P-gp, multidrug resistance-associated
      protein (MRP), lung resistance-related protein (LRP), breast cancer resistance
      protein (BCRP/MXR), drug resistance-associated protein (DRP), and ATP-binding
      cassette protein (ABCP). Several molecular probes, primer pairs, and monoclonal
      antibodies have been developed over the years to quantify the regulation and
      expression of these drug resistance markers in tumor cells. Methodologies have
      also been standardized to estimate the gene amplification, mRNA and protein
      expression, and functionality of drug resistance proteins in clinical specimens
      from cancer patients. Because of the recent developments in microarray
      technology, DNA and protein arrays against drug resistant genes are available
      commercially now. This review includes techniques for detection and
      quantification of the expression and function of these drug resistance genes in
      childhood renal tumors. Since these markers have clinical significance, currently
      available technology warrants the application of these markers in clinical
      oncology. Moreover, the first, second and third generation drug resistance
      modifiers have been developed over the past several years for overcoming drug
      resistance problem in tumor cells. Unfortunately, these reversing agents are yet
      to be proved successful clinically. Since treatment protocols are usually adopted
      from adult tumor patients into childhood population, clinical trials with
      modifying agents are yet to be undertaken and/or concluded in pediatric renal
      cancer patients. More clinical studies may be required to analyze the genes
      involved in the MDR of childhood renal cancer patients and trials have to be
      undertaken to evaluate the efficacy of MDR modifying agents in them, at least in
      parallel with adult patients.

PMID- 17430159
TI  - Drug-resistance in central nervous system tumors: from the traditional cell
      resistance model to the genetically driven approaches on therapy.
AB  - The advances in the cure rates observed in the oncology field in the past decades
      were not fully assembled by primary brain tumors. In this heterogeneous group of
      diseases, resistance to either chemotherapy or radiotherapy still is a major
      problem to be addressed. Several genetic and epigenetic events may directly
      influence the response to treatment in these tumors. Throughout recent
      discoveries, drug resistance in brain tumors was better understood as a final
      product of different and complexes pathways that interact and modulate cell
      performance to treatment. The last years experienced a new paradigm in the way
      brain tumor drug-resistance genes are elected out of the vast human genomic
      universe. In the former era, models of cell resistance that were documented on
      solid tumors other than brain were investigated at the central nervous system's
      counterpart. Nowadays, genomic-based hypothesis generation, supported by modern
      genetic technique tolls, seem effective in revealing new candidate-genes that
      might confer the resistance phenotype. Nevertheless, new treatment approaches and
      novel drugs based on the pharmacogenomic resistance profile, particularly for
      brain tumors, are just starting to become a reality for clinical purposes.

PMID- 17430160
TI  - Animal models to study plaque vulnerability.
AB  - The need to identify and characterize vulnerable atherosclerotic lesions in
      humans has lead to the development of various animal models of plaque
      vulnerability. In this review, current concepts of the vulnerable plaque as it
      leads to an acute coronary event are described, such as plaque rupture, erosion,
      intraplaque hemorrhage and neovascularization. Recently developed animal models
      that have attempted to reproduce these concepts are described and evaluated based
      on their suitability in the study of vulnerable plaques. Although certain
      features of plaque vulnerability have been reported in animal models, a model
      encompassing all aspects of the vulnerable plaque is lacking.

PMID- 17430161
TI  - Stabilizing the vulnerable plaque: the search for the magic bullet.

PMID- 17430162
TI  - Activation of the innate immune system in atherosclerotic disease.
AB  - Innate immunity is the first line of defence against invading micro-organisms.
      The family of Toll-like receptors (TLRs) recognizes pathogen-associated molecular
      patterns (PAMPs) that are carried by the invading micro-organisms. Infectious
      pathogens have been implicated to play an important role in atherosclerosis.
      Nowadays, evidence is accumulating that TLRs play an important role in the
      initiation and progression of atherosclerosis too. A lot is known about the
      exogenous ligands that are able to activate the TLRs, but it is also known that
      endogenous ligands have the capacity to activate TLRs when exogenous ligands are
      absent. Studies on knockout mice, epidemiological studies and even human
      polymorphism studies confirmed the important role of TLRs in development and
      progression of atherosclerotic disease. Studies with antagonists against TLR
      ligands and vaccination studies demonstrated that TLR signaling might be a
      potential target for intervention in the initiation and progression of
      atherosclerosis.

PMID- 17430163
TI  - Current diagnostic modalities for vulnerable plaque detection.
AB  - Rupture of vulnerable plaques is the main cause of acute coronary syndrome and
      myocardial infarction. Identification of vulnerable plaques is therefore
      essential to enable the development of treatment modalities to stabilize such
      plaques. Several diagnostic methods are currently tested to detect vulnerable
      plaques. Angiography has a low discriminatory power to identify the vulnerable
      plaque, but does provide information about the entire coronary tree and serves as
      guide for invasive imaging techniques and therapy. Angioscopy offers a direct
      visualization of the plaque surface and intra-luminal structures like thrombi and
      tears. However, angioscopy is difficult to perform, invasive and only the
      proximal part of the vessels can be investigated. IVUS (intravascular ultrasound)
      provides some insight into the composition of plaques. The detection of
      vulnerable plaques is mainly based on series of case reports with a lack of
      prospectivity and follow-up. Palpography, an IVUS derived technique, reveals
      information, which is not recognizable in IVUS. It can differentiate between
      deformable and non-deformable tissue, which enables the technique to detect
      vulnerable plaques with a positive predictive value. The clinical value of
      palpography is currently under investigation. Thermography assesses the
      temperature heterogeneity as an indicator of the metabolic state of the plaque. A
      coincidence of temperature rise and localization of vulnerable plaque was
      suggested. OCT (optical coherence tomography) can provide images with ultrahigh
      resolution utilizing the back-reflection of near-infrared light from optical
      interfaces in tissue. Drawbacks are the low penetration depth into tissue and the
      absorbance of light by blood. Raman spectroscopy can provide quantification about
      the molecular composition of the plaque. Long acquisition time, the low
      penetration depth and light absorbance by blood limit the performance of the
      technique. Another light emitting technique is NIR (near infrared spectroscopy),
      which identifies lipid loaded plaques and is tested currently in clinical trials.
      Non-invasive MRI (magnetic resonance imaging) and multislice spiral computed
      tomography (MSCT), with their excellent ability to identify lipid-rich tissue,
      have been utilized to characterize potentially vulnerable plaques foremost in non
      moving structures like the carotid arteries. Due to the resolution of the
      techniques small plaque structure cannot be assessed. The role of non-invasive
      imaging in vulnerable plaque detection is currently under investigation. Several
      invasive and non-invasive techniques are currently under development to assess
      the vulnerable plaque. Most of the techniques show exiting features, but none
      have proven their value in an extensive in vivo validation and all have a lack of
      prospective data.

PMID- 17430164
TI  - Pleiotropic effects of statins: stabilization of the vulnerable atherosclerotic
      plaque?
AB  - Acute coronary syndromes (ACS), i.e. unstable angina and myocardial infarction,
      are the leading causes of death in developed countries and developing countries
      alike. Lipid lowering intervention studies have demonstrated a 30% risk reduction
      in recurrent cardiovascular events and death, despite only modest improvement in
      angiographic stenosis. This discrepancy suggested that cholesterol lowering by
      statins may lead to stabilization of vulnerable plaques rather than reducing
      stenosis per se. The predominant effect of statins is to lower lipid levels by
      inhibiting cholesterol biosynthesis. Besides the lipid lowering effects, statins
      have also been shown to modulate the inflammatory status and improve endothelial
      function amongst others, commonly referred to as "pleiotropic effects". In the
      present review we will discuss different determinants which lead to plaque
      vulnerability and subsequently we will expand on the plaque stabilizing or
      "pleiotropic" effects of statin treatment.

PMID- 17430165
TI  - Oxidized LDL antibodies in treatment and risk assessment of atherosclerosis and
      associated cardiovascular disease.
AB  - Immune responses against oxidized forms of LDL play a critical role in activation
      and regulation of the inflammatory process that characterizes all stages of
      atherosclerosis. In humans oxidized LDL is targeted by both IgM and IgG
      autoantibodies. Immunization of hypercholesterolemic animals with oxidized LDL
      has been shown to inhibit atherosclerosis demonstrating that at least some of
      these immune responses have a protective effect. The identification of the
      structures in oxidized LDL that are responsible for activation of immunity has
      made it possible to develop novel therapeutic approaches for treatment of
      atherosclerosis based on active (vaccines) and passive (antibodies) immunization.
      Studies performed in atherosclerosis-prone mice demonstrate that both peptide
      based vaccines and recombinant IgG targeting epitopes in oxidized LDL
      significantly reduce atherosclerosis. There is also evidence antibodies against
      oxidized LDL could also be used for imaging atherosclerosis.

PMID- 17430166
TI  - Apolipoprotein A-I/HDL infusion therapy for plaque stabilization-regression: a
      novel therapeutic approach.
AB  - LDL-lowering therapies, predominantly involving statins, have been shown to
      significantly reduce cardiovascular events in asymptomatic subjects as well as in
      subjects with clinically established atherosclerotic cardiovascular disease.
      However, despite statin therapy, significant number of cardiovascular events
      continue to occur indicating the need for additional targets for atherosclerosis
      management. A number of pre-clinical studies have suggested that several HDL
      based therapies have the potential to stabilize or regress atherosclerosis
      consistent with epidemiologic evidence of an inverse relationship between
      coronary heart disease and HDL cholesterol levels. One such therapeutic approach
      involves direct infusion of HDL or HDL like molecules for rapid remodeling and
      stabilization of atherosclerosis. Pre-clinical and proof of concept type
      preliminary clinical studies suggest the feasibility and potential efficacy of
      this emerging new therapeutic paradigm.

PMID- 17430167
TI  - Chemokines and atherosclerotic plaque progression: towards therapeutic targeting?
AB  - Atherosclerosis is currently viewed as an inflammatory disease in which the
      initiation and progression of the atherosclerotic plaque towards a rupture prone,
      unstable plaque is driven by leukocyte recruitment mediated by various
      inflammatory mediators. Recently, interest in chemotactic cytokines or chemokines
      with regard to atherosclerosis has been growing as chemokines mediate the influx
      of leukocytes that is typical of atherothrombosis. The activity of the majority
      of chemokines is overlapping and chemokines are not only produced by the various
      cellular constituents of the atherosclerotic plaque but also by activated
      platelets. Consequently, the direct influence of individual chemokines on plaque
      destabilisation and rupture is widespread and rather unclear. Experimental
      research has already established the role of a number of chemokines in advanced
      atherosclerosis. Nevertheless, given the complexity and size of the chemokine
      family, further screening of cardiovascular disease for chemokine level and
      genetic polymorphisms for chemokines will be warranted as the search for viable
      biomarkers of plaque destabilization as well as novel therapeutic targets for
      specific atheroregressive therapeutic compounds is ongoing. With regard to the
      latter, clinical trials with specific chemokine inhibitory strategies, like
      chemokine receptor antagonists, are already underway in other inflammatory
      disorders. Summarizing, chemokine inhibition likely constitutes an important
      therapeutic option next to already established drugs in the management of
      cardiovascular disease.

PMID- 17430168
TI  - Restoring the dysfunctional endothelium.
AB  - Nowadays the endothelium is considered a key determinant of vascular health. NO
      is the principal mediator of all endothelial protective effects, due to its
      antiinflammatory, antiproliferative, immunomodulatory and vasorelaxant
      properties. On the contrary, a growing body of evidence suggests that endothelial
      dysfunction is associated with cardiovascular events. Emerging data suggest that
      acute coronary syndromes (ACS) may involve a complex interplay between
      endothelial dysfunction, inflammation and thrombosis. Despite the success in
      reducing the mortality from acute cardiovascular events, the incidence of
      cardiovascular disease and its complication continues to increase. New insights
      into mechanisms of endothelial dysfunction, such as a better understanding of the
      regulation of vascular sources of oxygen radicals, may lead to novel therapeutic
      strategies with the potential to improve prognosis. The key pharmacological
      agents that improve clinical outcome in high-risk patients are statins, ACE
      inhibitors or angiotensin receptor antagonists. Compelling scientific evidence
      suggests that these medications are effective in improving endothelial function.
      The present review focuses on the potential importance of benefits on endothelium
      of these medicaments in the management of acute coronary syndromes.

PMID- 17430169
TI  - Multi-constituent cardiovascular pills (MCCP)--challenges and promises of
      population-based prophylactic drug therapy for prevention of heart attack.
AB  - Risk factors for atherosclerotic cardiovascular disease (CVD) are highly co
      prevalent but poorly identified and treated. The Screening for Heart Attack
      Prevention and Education (SHAPE) Task Force from the Association for Eradication
      of Heart Attack (AEHA) has recently proposed a new strategy that recommends
      screening for subclinical atherosclerosis and implementing aggressive treatment
      of "vulnerable patients". The Task Force has also envisioned future developments
      that may shift mass screening strategies to mass prophylactic therapy. The
      "Polypill" concept, introduced by Wald and Law suggests a combination of statin,
      low-dose antihypertensives, aspirin and folic acid, in a single pill, taken
      prophylactically by high risk population can cut CVD event rates by as much as
      80%. In this communication, we review the challenges and promises of such a
      strategy. "Polypill" is but one of an astronomical number of possible
      multiconstituent pills (MCCP). Attractive as the MCCP concept is, it lacks
      evidence from randomized controlled trials, and begs numerous questions about the
      credibility of the concept, the design and synthesis of such complex pills,
      pharmacokinetics, pharmacodynamics, bioequivalence, "class" vs. unique
      properties, interactions, evidence of clinical efficacy and safety, regulatory
      approval, post-marketing surveillance, prescription vs. over-the-counter use,
      responsibility for initiating and monitoring therapy, patient education,
      counterfeiting and importation, reimbursement, advertisement, patent protection,
      commercial viability, etc. If these issues are favorably addressed, MCCP stand to
      dramatically change the manner in which CVD is prevented particularly in
      developing societies. Notwithstanding, assuming low commercial interests,
      realizing the promises of MCCP will demand serious attention from national public
      health policymakers. The clinical and regulatory implications of population-based
      secondary prevention (which rely on a different evidence base, and in which
      entirely different risk-benefit and cost-effectiveness considerations apply)
      remain issues for active debate.

PMID- 17430171
TI  - Vasoactive intestinal peptide in neurodevelopmental disorders: therapeutic
      potential.
AB  - Vasoactive intestinal peptide (VIP) mediates important events during the
      development of the nervous system. VIP can stimulate neuronogenesis as well as
      differentiation and neurite outgrowth; it can promote the survival of neurons and
      assist in neuronal repair; it is also anti-inflammatory and can modulate immune
      responses. In addition, VIP is necessary for the normal growth and development of
      the early postimplantation mouse embryo during the period when the major
      embryonic events are neural tube formation, neuronogenesis and expansion of the
      vascular system. Receptors for VIP appear during early postimplantation
      embryogenesis in the rodent and exhibit changing localization patterns throughout
      the development of the brain. During embryogenesis, unregulated VIP may have
      major and permanent consequences on the formation of the brain and may be a
      participating factor in disorders of neurodevelopment. VIP has been linked to
      autism, Down syndrome and fetal alcohol syndrome. This paper will review the role
      of VIP in neurodevelopment, its known involvement in neurodevelopmental disorders
      and propose ways in which VIP might be of therapeutic value.

PMID- 17430172
TI  - NAP and ADNF-9 protect normal and Down's syndrome cortical neurons from oxidative
      damage and apoptosis.
AB  - NAP (Asn-Ala-Pro-Val-Ser-Ile-Pro-Gln, single letter code: NAPVSIPQ) and ADNF-9
      (activity-dependent neurotrophic factor-9; Ser-Ala-Leu-Leu-Arg-Ser-Ile-Pro-Ala;
      single letter code: SALLRSIPA) are peptides derived from naturally occurring
      glial proteins that have shown neuroprotection in rodent model systems. Here, the
      neuroprotective activity of ADNF-9 and NAP was tested in two human models of
      neuronal degeneration in culture mediated by oxidative stress: normal human
      cortical neurons treated with H2O2 and Down's syndrome (DS) cortical neurons.
      Incubation of normal cortical neurons with 50 microM H2O2 for 1 hour resulted in
      morphological and structural changes consistent with neuronal degeneration and
      loss of viability of more than 60% of the neurons present in the culture.
      Addition of ADNF-9 or NAP at femtomolar concentrations resulted in significant
      increases in survival of normal neurons treated with H2O2. Femtomolar
      concentrations of ADNF-9 or NAP exhibited a similar neuroprotective efficacy,
      comparable to the antioxidant N-tert-butyl-2-sulpho-phenylnitrone at 100 microM
      (s-PBN). Treatment of DS cortical neurons with ADNF-9 or NAP resulted in a
      significant increase in neuronal survival as well as reduction of degenerative
      morphological changes. The results suggest that ADNF-9 and NAP possess potent
      neuroprotective properties against oxidative damage in human neurons that may be
      useful to preserve neuronal function and prevent neuronal death associated with
      chronic neurodegenerative disorders.

PMID- 17430173
TI  - Vasoactive intestinal peptide receptors: a molecular target in breast and lung
      cancer.
AB  - Vasoactive intestinal peptide (VIP) receptors are present in the normal brain as
      well as periphery, and cancer cells. Three major types of VIP receptors include
      the VPAC(1), VPAC(2) and PAC(1) receptors. VPAC(1) receptors are present in high
      densities on human lung and breast cancer cells lines and biopsy specimens.
      Radiolabeled VIP analogues have been developed for imaging of lung and breast
      cancer. Synthetic VIP receptor antagonists inhibit the proliferation and
      potentiate the ability of chemotherapeutic agents to cause apoptosis of lung and
      breast cancer cells. VIP-chemotherapeutic conjugates have been synthesized which
      bind to VPAC(1) receptors and are internalized, resulting in the killing of lung
      and breast cancer cells. These results suggest that VPAC(1) receptors may be
      molecular targets for diagnosis, prevention and treatment of breast cancer as
      well as lung cancer.

PMID- 17430174
TI  - PACAP in the glucose and energy homeostasis: physiological role and therapeutic
      potential.
AB  - Pituitary adenylate cyclase activating polypeptide (PACAP) is a ubiquitous
      neuropeptide in the central and peripheral nervous systems. PACAP is also
      produced by pancreatic islet cells. PACAP regulates the glucose and energy
      metabolism at multiple processes in several tissues. At postprandial states,
      PACAP potentiates both insulin release from pancreatic beta-cells and insulin
      action in adipocytes, contributing to energy storage. At fasting states, PACAP on
      the one hand promotes feeding behavior by activating neuropeptide Y neurons in
      the hypothalamic feeding center, arcuate nucleus, and on the other hand
      stimulates secretion of catecholamine and glucagon and thereby induces lipolysis
      in adipocytes and glucose output from liver. Thus, PACAP plays an integrative
      role in the glucose and energy homeostasis. Dysfunction of expression, secretion
      and/or action of PACAP might be involved in the type 2 diabetes and metabolic
      syndrome. PACAP receptor subtype-specific agonists and/or antagonists are hopeful
      therapeutic agents.

PMID- 17430175
TI  - Therapeutical approaches of vasoactive intestinal peptide as a pleiotropic
      immunomodulator.
AB  - The vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase
      activating polypeptide (PACAP) are two neuropeptides belonging to the
      VIP/secretin/glucagon family of peptides. VIP/PACAP are present and released from
      both innervation and immune cells, particularly Th2 cells, and exert a wide
      spectrum of immunological functions controlling the homeostasis of immune system
      through different receptors expressed in various immunocompetent cells. VIP/PACAP
      have a general anti-inflammatory effect, both in innate and adaptive immunity. In
      innate immunity, VIP/PACAP inhibit the production of pro-inflammatory cytokines
      and chemokines from macrophages, microglia and dendritic cells. In addition,
      VIP/PACAP reduce the expression of costimulatory molecules (particularly CD80 and
      CD86) on the antigen-presenting cells, and therefore reduce stimulation of
      antigen-specific CD4(+) T cells. In terms of adaptive immunity, VIP/PACAP promote
      Th2-type responses, and reduce the pro-inflammatory Th1-type responses. Several
      of the molecular mechanisms involved in the inhibition of cytokine and chemokine
      expression, and in the preferential development and/or survival of Th2 effectors,
      are perfectly known. Therefore, VIP/PACAP and analogues have been recently
      proposed as very promising candidates, alternative to other existing treatments,
      for treating acute and chronic inflammatory and autoimmune diseases, such as
      septic shock, rheumatoid arthritis, multiple sclerosis, Parkinson's disease,
      Crohn disease, or autoimmune diabetes. The aim of this review is firstly to
      update our knowledge of the cellular and molecular events relevant to VIP
      function on the immune system; and secondly to gather together recent data that
      support its role as a type 2 cytokine. Recognition of the central functions VIP
      plays in cellular processes is focusing our attention on this "very important
      peptide" as an exciting new candidate for therapeutic intervention and drug
      development.

PMID- 17430176
TI  - Carotid artery atherosclerosis: what is the evidence for drug action?
AB  - Carotid artery disease is a well-established cause of cerebrovascular events.
      This risk is predicted by the severity of stenosis and other plaque
      characteristics that can be documented using imaging techniques. Among these
      techniques, ultrasound is the most widely available. Increased carotid intima
      media thickness (IMT) measured ultrasonically is associated with a higher risk
      for cerebrovascular as well as coronary heart disease. Furthermore, it is
      increasingly recognized that echolucent and heterogeneous carotid plaques in
      patients with high-grade carotid stenosis are associated with a greater risk for
      cerebrovascular events. Several local and systemic factors can influence plaque
      stability. Identifying the high-risk carotid plaque could improve selection for
      vascular intervention (surgery/angioplasty) and increase cost-effectiveness.
      Aggressive medical treatment should always be provided for these high-risk
      patients. For example, lipid-lowering, anthihypertensive and antiplatelet drugs
      decrease the carotid IMT, stabilize carotid plaques or reduce the risk of
      cerebrovascular and systemic events. Continuously evolving technology will lead
      to more accurate identification of high-risk carotid plaques. A combination of
      comprehensive non- or minimally-invasive imaging techniques together with
      measuring clinical and systemic biochemical markers of risk may facilitate the
      identification of the vulnerable plaque in the vulnerable patient, and help
      select the best treatment options.

PMID- 17430177
TI  - Targeting the methyl erythritol phosphate (MEP) pathway for novel antimalarial,
      antibacterial and herbicidal drug discovery: inhibition of 1-deoxy-D-xylulose-5
      phosphate reductoisomerase (DXR) enzyme.
AB  - The 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway for isoprenoid biosynthesis
      has come under increased scrutiny as a target for novel antimalarial,
      antibacterial and herbicidal agents. 1-Deoxy-D-xylulose 5-phosphate
      reductoisomerase (DXR) is a key enzyme of the pathway that catalyzes the
      rearrangement and nicotinamide adenine dinucleotide phosphate (NADPH)-dependent
      reduction of 1-deoxy-D-xylulose 5-phosphate (DXP) to MEP. The unique properties
      of DXR make it a remarkable and rational target for drug design. First, it is a
      vital enzyme for synthesis of isoprenoids in algae, plants, several eubacteria
      including the pathogenic bacteria like Bacillus anthracis, Helicobacter pylori,
      Yersinia pestis, Mycobacterium tuberculosis and the malarial parasite, Plasmodium
      falciparum. Second, there are no functional equivalents to DXR in humans, making
      it an attractive target for therapeutic intervention. Third, DXR appears to be a
      valid target and the results from fosmidomycin (1), the only available DXR
      inhibitor under clinical trials, suggests synergistic effects with the
      lincosamide antibiotics, lincomycin and clindamycin. Despite drug design efforts
      in this area, no successful drug specifically designed to inhibit DXR has emerged
      yet. This review summarizes the recent and promising developments with respect to
      the current knowledge of the MEP pathway with emphasis on the understanding of
      the structure and the catalytic mechanism of the DXR enzyme and the global quest
      for therapeutically useful inhibitors of DXR.

PMID- 17430178
TI  - Magnetic carriers: a promising device for targeting drugs into the human body.
AB  - Suboptimal disposition behavior of drugs requires innovative delivery approaches.
      Magnetic drug targeting seems to be a promising one. Magnetic particles develop
      magnetic polarization and magnetophoretic mobility, and because of such unique
      properties, these carriers may be eligible candidates for delivering drugs to
      specific locations within the body. Their special properties also allow other
      uses, such as those in magnetic separation, hyperthermia, and magnetic resonance
      imaging. This review focuses on a brief discussion of magnetic drug targeting,
      the properties and fate of magnetic carriers, the methods used to produce and
      characterize them, and their other uses in biotechnology.

PMID- 17430180
TI  - Angiotensin converting enzyme inhibitory peptides derived from food proteins:
      biochemistry, bioactivity and production.
AB  - Food proteins contain latent biofunctional peptide sequences within their primary
      structures which may have the ability to exert a physiological response in vivo.
      A large range of biofunctional peptides have been isolated from food proteins
      including opioid, immunomodulatory, antimicrobial, mineral binding, growth and
      muscle stimulating, anti-cancer, proteinase and angiotensin converting enzyme
      (ACE, EC 3.4.15.1) inhibitory peptides. The biofunctional peptide activity
      currently most studied in food proteins appears to be those that inhibit ACE. ACE
      plays a central role in the regulation of blood pressure (BP) through the
      production of the potent vasoconstrictor, angiotensin (Ang) II , and the
      degradation of the vasodilator, bradykinin (BK). ACE inhibitory peptides may
      therefore have the ability to lower BP in vivo by limiting the vasoconstrictory
      effects of Ang II and by potentiating the vasodilatory effects of BK. These ACE
      inhibitory peptides can be enzymatically released from intact proteins in vitro
      and in vivo during food processing and gastrointestinal digestion, respectively.
      ACE inhibitory peptides may be generated in or incorporated into functional foods
      in the development of 'natural' beneficial health products. Several products are
      currently on the market or are in development that contain peptide sequences
      which have ACE inhibitory properties. Detailed human studies are required in
      order to demonstrate the efficacy of these bioactive peptides prior to their
      widespread utilisation as physiologically beneficial functional foods/food
      ingredients.

PMID- 17430181
TI  - Casein phosphopeptides in oral health--chemistry and clinical applications.
AB  - The casein phosphopeptides (CPP) are derived from the milk protein casein by
      tryptic digestion. The CPP, containing the sequence -Pse-Pse-Pse-Glu-Glu- where
      Pse is a phosphoseryl residue, stabilize calcium and phosphate ions in aqueous
      solution and make these essential nutrients bioavailable. Under alkaline
      conditions the calcium phosphate is present as an alkaline amorphous phase
      complexed by the CPP, referred to as casein phosphopeptide-amorphous calcium
      phosphate (CPP-ACP). The CPP-ACP complexes readily incorporate fluoride ions
      forming casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP). A
      mechanism is discussed which provides a rationale for the ability of the CPP-ACP
      to remineralize carious lesions in dental enamel. Clinical applications of the
      CPP-ACP as agents in the treatment of dental caries and other hypomineralized
      conditions are reviewed. It is concluded that the CPP are a safe and novel
      carrier for calcium, phosphate and hydroxide (fluoride) ions to promote enamel
      remineralization with application in oral care products, dental professional
      products and foodstuffs.

PMID- 17430182
TI  - Antibiotic properties and applications of lactoferrin.
AB  - Lactoferrin (Lf), a mammalian iron scavenging defense protein, constitutively is
      present in exocrine secretions that consistently are exposed to microbial flora:
      milk, tears, tubotympanum and nasal exudate, saliva, bronchial mucus,
      gastrointestinal fluids, cervicovaginal mucus, and seminal fluid. Additionally,
      Lf is promptly delivered by circulating neutrophils to sites of microbial
      invasion. At these sites, the protein effectively scavenges iron at pH values as
      low as 3.5. Recombinant bovine and human lactoferrin is now available for
      development into nutraceutical/preservative/pharmaceutical products. Among
      conditions for which the products are being investigated are: angiogenesis; bone
      remodeling; food preservation; infection in animals, humans, plants; neoplasia in
      animals, humans; inflammation in intestine, joints; wound healing; as well as
      enhancement of antimicrobial and antineoplastic drugs, and prevention of iron
      induced oxidation of milk formula.

PMID- 17430183
TI  - A role for milk proteins and their peptides in cancer prevention.
AB  - A role for the amount and type of dietary protein in the etiology of cancer has
      not been studied extensively. Nevertheless, there is no compelling evidence from
      epidemiological studies to indicate that protein, at levels usually consumed, is
      a risk factor for cancer. On the other hand, animal studies suggest that certain
      peptides and amino acids derived from dietary proteins may influence
      carcinogenesis. The predominant protein in milk, casein, its peptides, but not
      liberated amino acids, have antimutagenic properties. Animal models, usually for
      colon and mammary tumorigenesis, nearly always show that whey protein is superior
      to other dietary proteins for suppression of tumour development. This benefit is
      attributed to its high content of cystine/cysteine and gamma-glutamylcyst(e)ine
      dipeptides, which are efficient substrates for the synthesis of glutathione.
      Glutathione is an ubiquitous cellular antioxidant that directly or through its
      associated enzymes destroys reactive oxygen species, detoxifies carcinogens,
      maintains proteins in a reduced state and ensures a competent immune system.
      Various experiments showed that tumour prevention by dietary whey protein was
      accompanied by increased glutathione levels in serum and tissues as well as
      enhanced splenic lymphocyte proliferation, phagocytosis and natural killer, T
      helper and cytotoxic T cell activity. Whey protein components, beta
      lactoglobulin, alpha-lactalbumin and serum albumin were studied infrequently, but
      results suggest they have anticancer potential. The minor component lactoferrin
      has received the most attention; it inhibits intestinal tumours and perhaps
      tumours at other sites. Lactoferrin acts by induction of apoptosis, inhibition of
      angiogenesis, modulation of carcinogen metabolising enzymes and perhaps acting as
      an iron scavenger. Supplementing cows with selenium increases the content of
      selenoproteins in milk, which on isolation inhibited colon tumorigenesis in rats.

PMID- 17430184
TI  - Technological options for the production of health-promoting proteins and
      peptides derived from milk and colostrum.
AB  - Milk proteins are known to exert a wide range of nutritional, functional and
      biological activities. Apart from being a balanced source of valuable amino
      acids, milk proteins contribute to the consistency and sensory properties of
      various dairy products. Furthermore, many milk proteins possess specific
      biological properties which make them potential ingredients of health-promoting
      foods. These properties are attributed to both native protein molecules and to
      physiologically active peptides encrypted in the protein molecules. Considerable
      progress has been made over the last twenty years in technologies aimed at
      separation, fractionation and isolation in a purified form of many interesting
      proteins occurring in bovine colostrum and milk. Industrial-scale methods have
      been developed for native whey proteins such as immunoglobulins, lactoferrin,
      lactoperoxidase, alpha-lactalbumin and beta-lactoglobulin. Their large-scale
      manufacture and commercial exploitation is still limited although validated
      research data about their physiological health benefits is rapidly accumulating.
      Promising product concepts and novel fields of use have emerged recently, and
      some of these molecules have already found commercial applications. The same
      applies to bioactive peptides derived from different milk proteins. Active
      peptides can be liberated during gastrointestinal digestion or milk fermentation
      with proteolytic enzymes. Such peptides may exert a number of physiological
      effects in vivo on the gastrointestinal, cardiovascular, endocrine, immune,
      nervous and other body systems. However, at present the industrial-scale
      production of such peptides is limited by a lack of suitable technologies. On the
      other hand, a number of bioactive peptides have been identified in fermented
      dairy products, and there are already a few commercial dairy products enriched
      with blood pressure-reducing milk protein peptides. There is a need to develop
      methods to optimise the activity of bioactive peptides in food systems and to
      enable their optimum utilisation in the body. This review highlights existing
      modern technologies applicable for the isolation of bioactive native proteins and
      peptides derived from bovine colostrum, milk and cheese whey, and discusses
      aspects of their current and potential applications for human nutrition and
      promotion of human health.

PMID- 17430185
TI  - Targeting antioxidants to mitochondria: a potential new therapeutic strategy for
      cardiovascular diseases.
AB  - Mitochondria produce large amounts of free radicals and play an important role in
      the life and death of a cell. Thus, mitochondrial oxidative damage and
      dysfunction contribute to a number of cell pathologies that manifest themselves
      through a range of conditions including ischemia-reperfusion injury, sepsis,
      diabetes, atherosclerosis and, consequently, cardiovascular diseases (CVD). In
      fact, endothelial dysfunction, characterized by a loss of nitric oxide (NO)
      bioactivity, occurs early on in the development of atherosclerosis, and
      determines future vascular complications. Although the molecular mechanisms
      responsible for mitochondria-mediated disease processes are not yet clear,
      oxidative stress seems to play an important role. This review considers the
      process of CVD from a mitochondrial perspective. Accordingly, strategies for the
      targeted delivery of antioxidants to mitochondria are being developed. In this
      review, we will provide a summary of the following areas: the cellular metabolism
      of reactive oxygen species (ROS) and its role in pathophysiological processes
      such as CVD; currently available antioxidants and possible reasons for their
      efficacy and inefficacy in ameliorating oxidative stress-mediated diseases;
      recent developments in mitochondrially-targeted antioxidants that concentrate on
      the matrix-facing surface of the inner mitochondrial membrane and therefore
      protect against mitochondrial oxidative damage, and their therapeutic potential
      for future treatment of CVDs. More pre-clinical and clinical studies, however,
      are necessary in order to evaluate the effectiveness and toxicity of
      mitochondrially-targeted antioxidants.

PMID- 17430187
TI  - Egg proteins and peptides in human health--chemistry, bioactivity and production.
AB  - Egg is the largest biological cell known which originates from one cell division
      and is composed of various important chemical substances that form the basis of
      life. The avian egg is an important source of nutrients, containing all of the
      proteins, lipids, vitamins, minerals and growth factors required by the
      developing embryo, as well as a number of defence factors to protect against
      bacterial and viral infection. This review mainly focuses on biological
      activities of proteins and peptides derived from egg components. Several
      biological activities have now been associated with egg components, including
      novel anti-microbial activities, anti-adhesive properties, immunomodulatory, anti
      cancer, and anti-hypertensive activities, anti-oxidant properties, protease
      inhibitors, nutrient bioavailability and functional lipids, highlighting the
      importance of egg and egg components in human health, and disease prevention and
      treatment.

PMID- 17430186
TI  - Aquaretic agents: what's beyond the treatment of hyponatremia?
AB  - Unlike the more commonly used diuretics, aquaretic agents can induce an increase
      in urinary volume without incurring a loss of electrolytes. These molecules
      belong to a family of vasopressin receptor antagonists, V2 in particular, that
      regulate optional renal water re-absorption via the synthesis and expression of
      aquaporin-2. In view of their properties, they have become the agent of choice in
      the treatment of hyponatremic states with water retention, and different studies
      have demonstrated that they are more effective and practical to use than other
      traditional approaches in the treatment of diseases such as cirrhosis-related
      ascites, SIADH and, above all, heart failure. However, the future probably holds
      the promise of new and unexpected applications for this type of drug in the
      treatment of several conditions, including polycystic kidney and glomerular
      disease, glaucoma and Meniere's syndrome.

PMID- 17430188
TI  - Food-derived peptides and intestinal functions.
AB  - The intestines are an important organ responsible for nutrient absorption,
      metabolism and recognition of food signals. The organ also acts as a physical and
      biological barrier against harmful substances including food pathogens and
      environmental chemicals. Food-derived peptides with a variety of physiological
      functions have been discovered in the past several decades. Although dietary
      peptides would mostly be hydrolyzed by digestive enzymes in the intestinal tract,
      possibly losing their biological functions during this step, some could be
      absorbed intact and act in their target organs. The intestines are also one of
      the targets for functional peptides. The intestine-modulatory peptides can be
      classified into two categories: (1) peptides that express their functions in the
      intestinal tract and (2) peptides that modulate intestinal epithelial cell
      functions. The 1(st) group includes peptides that regulate the intestinal
      absorption of nutrients. Enhancing mineral absorption by casein phosphopeptides,
      and suppressing dietary cholesterol absorption by soybean peptides are typical
      examples. The 2(nd) group includes such glutamine-containing peptides as Ala-Gln
      that show interesting properties in preventing and/or repairing damage caused by
      oxidative stress and inflammatory reactions. We have found that carinosine (beta
      Ala-His) suppressed the secretion of such inflammatory cytokines as IL-8 in human
      intestinal epithelial cells, suggesting its anti-inflammatory function in the
      intestines. Peptides that modulate such intestinal immune functions as secretory
      IgA production and cytokine secretion, and opioid peptides regulating intestinal
      motility are also included in this group. These intestine-modulatory peptides
      would be useful as ingredients of future functional foods to prevent lifestyle
      related diseases and promote gut health.

PMID- 17430189
TI  - Cytotoxic and allergenic potential of bioactive proteins and peptides.
AB  - This review article deals with the assessment of cytotoxic and allergenic
      potential of bioactive proteins and peptides. It is evident that 'novel' foods or
      nutraceuticals containing bioactive proteins and peptides must fulfill their
      proposed "health claim". Furthermore, there is a need to assess their potential
      to exert adverse effects before they can be made widely available to consumers. A
      brief overview of compounds (i.e. proteins and peptides of animal and plant
      origin) and mechanisms involved in cytotoxic and allergenic (adverse) reactions
      is given along with some recent results obtained from ongoing studies. There are
      numerous proteins and peptides of plant and animal origin that are known to
      exhibit cytotoxic effects. There is evidence that many cytotoxic compounds
      described in the literature exclusively affect malignant cells leading to the
      assumption that a cancer protective effect could exist for such bioactive
      proteins and peptides. All the constituents that are responsible for the
      allergenicity of foods (as well as of pollens) are proteinaceous in nature. Some
      protein breakdown products, i.e. peptide fragments, may conserve part of the
      allergenicity of the native protein and thus can also be considered as allergens.
      The molecular basis of IgE recognition underlying cow's milk protein allergy is
      described. Some results from studies on volunteers fed caseinophosphopeptides or
      potentially hypotensive milk protein hydrolysates illustrate the major difference
      between allergenicity and immunogenicity. The data presented on the relationship
      between the structure of food proteins and peptides and their allergenicity shows
      the difficulty in trying to assess the "non-allergenicity" of products derived
      from an allergenic source, even if the process used involved extensive hydrolysis
      of the native protein(s). A 'weight of evidence approach' for assessing the
      potential allergenicity of a novel protein with no history of prior allergenicity
      is also presented with regard to the current EU Regulations.

PMID- 17430190
TI  - Nucleoprotein-derived and unbound ribonucleosides: bioactivity and potential
      applications.
AB  - Naturally occurring and chemically modified ribonucleosides have interesting
      bioactive effects. Dietary ribonucleosides are ingested mainly as nucleoproteins
      and are converted in the course of intestinal digestion to monomeric compounds.
      Different bioactive effects of dietary ribonucleosides have been described,
      including the ability to enhance gut growth and maturation and to increase iron
      absorption. Cytochemical studies with human cells showed that several
      ribonucleosides can induce apoptosis in human cells, and therefore may be
      potentially anticancerogenic compounds. Even if suboptimal concentrations of
      single bioactive nucleo compounds are available from food, the total content of
      different bioactive ribonucleosides may reach physiologically effective
      concentrations in vivo where intestinal cells may represent the main target sites
      of a selective apoptotic activity. Modified ribonucleosides serve as valuable
      pathobiochemical marker molecules for cancer. Chemically modified ribonucleosides
      have already found interesting applications as pharmaceutically active compounds
      in the treatment of different illnesses including AIDS. Regarding therapeutic and
      pharmaceutical aspects, further studies are required to evaluate the bioactive
      efficacy of indigenous ribonucleosides. The findings demonstrate the great
      variety of potential applications of ribonucleosides, e.g. in functional foods as
      well as pharmaceutical preparations.

PMID- 17430191
TI  - Poly(ADP-ribose) polymerase inhibitors: new pharmacological functions and
      potential clinical implications.
AB  - Poly(ADP-ribose) polymerase (PARP) comprise of a family of enzymes which
      catalyses poly(ADP-ribosyl)ation of DNA-binding proteins. To date, seven isoforms
      have been identified: PARP-1, PARP-2, PARP-3, PARP-4 (Vault-PARP), PARP-5
      (Tankyrases), PARP-7 and PARP-10 with structural domains and different functions.
      PARP-1, the best characterised member, works as a DNA damage nick-sensor protein
      that uses beta-NAD(+) to form polymers of ADP-ribose and has been implicated in
      DNA repair, maintenance of genomic integrity and mammalian longevity. The
      generation of free radicals, reactive oxygen species, and peroxynitrite causes
      overactivation of PARP resulting in the depletion of NAD(+) and ATP and
      consequently in necrotic cell death and organ dysfunction. PARP has also been
      involved in the up-regulation of numerous pro-inflammatory genes through the
      activation of several transcription nuclear factors. Thus, PARP plays an
      important role in the pathogenesis of several diseases, such as, stroke,
      myocardial infarction, circulatory shock, diabetes, neurodegenerative disorders,
      including Parkinson and Alzheimer diseases, allergy, colitis and other
      inflammatory disorders. Pharmacological modulation of PARP activity may
      constitute a suitable target to enhance the cytotoxicity of certain DNA-damaging
      anticancer drugs. Also, PARP inhibition may be a viable strategy to control viral
      infections. This review is intended to provide an appreciation of new
      pharmacological perspectives of these remarkable drugs, summarize novel
      underlying mechanisms and discuss their potential clinical implications.

PMID- 17430192
TI  - Design of new oxazaphosphorine anticancer drugs.
AB  - The oxazaphosphorines including cyclophosphamide (CPA, Cytoxan, or Neosar),
      ifosfamide (IFO, Ifex) and trofosfamide (Ixoten) represent an important group of
      therapeutic agents due to their substantial antitumor and immunomodulating
      activity. However, several intrinsic limitations have been uncounted during the
      clinical use of these oxazaphosphorines, including substantial pharmacokinetic
      variability, resistance and severe host toxicity. To circumvent these problems,
      new oxazaphosphorines derivatives have been designed and evaluated with an
      attempt to improve the selectivity and response with reduced host toxicity. These
      include mafosfamide (NSC 345842), glufosfamide (D19575, beta-D
      glucosylisophosphoramide mustard), S-(-)-bromofosfamide (CBM-11), NSC 612567
      (aldophosphamide perhydrothiazine) and NSC 613060 (aldophosphamide thiazolidine).
      Mafosfamide is an oxazaphosphorine analog that is a chemically stable 4
      thioethane sulfonic acid salt of 4-hydroxy-CPA. Glufosfamide is IFO derivative in
      which the isophosphoramide mustard, the alkylating metabolite of IFO, is
      glycosidically linked to a beta-D-glucose molecule. Phase II studies of
      glufosfamide in the treatment of pancreatic cancer, non-small cell lung cancer
      (NCSLC), and recurrent glioblastoma multiform (GBM) have recently completed and
      Phase III trials are ongoing, while Phase I studies of intrathecal mafosfamide
      have recently completed for the treatment of meningeal malignancy secondary to
      leukemia, lymphoma, or solid tumors. S-(-)-bromofosfamide is a bromine
      substituted IFO analog being evaluated in a few Phase I clinical trials. The
      synthesis and development of novel oxazaphosphorine analogs with favourable
      pharmacokinetic and pharmacodynamic properties still constitutes a great
      challenge for medicinal chemists and cancer pharmacologists.

PMID- 17430194
TI  - Predicting experimental properties of proteins from sequence by machine learning
      techniques.
AB  - Efficient target selection methods are an important prerequisite for increasing
      the success rate and reducing the cost of high-throughput structural genomics
      efforts. There is a high demand for sequence-based methods capable of predicting
      experimentally tractable proteins and filtering out potentially difficult targets
      at different stages of the structural genomic pipeline. Simple empirical rules
      based on anecdotal evidence are being increasingly superseded by rigorous machine
      learning algorithms. Although the simplicity of less advanced methods makes them
      more human understandable, more sophisticated formalized algorithms possess
      superior classification power. The quickly growing corpus of experimental success
      and failure data gathered by structural genomics consortia creates a unique
      opportunity for retrospective data mining using machine learning techniques and
      results in increased quality of classifiers. For example, the current solubility
      prediction methods are reaching the accuracy of over 70%. Furthermore, automated
      feature selection leads to better insight into the nature of the correlation
      between amino acid sequence and experimental outcome. In this review we summarize
      methods for predicting experimental success in cloning, expression, soluble
      expression, purification and crystallization of proteins with a special focus on
      publicly available resources. We also describe experimental data repositories and
      machine learning techniques used for classification and feature selection.

PMID- 17430195
TI  - Predicting protein disorder and induced folding: from theoretical principles to
      practical applications.
AB  - In the last years there has been an increasing amount of experimental evidence
      pointing out that a large number of proteins are either fully or partially
      disordered (unstructured). Intrinsically disordered proteins are ubiquitary
      proteins that fulfil essential biological functions while lacking highly
      populated and uniform secondary and tertiary structure under physiological
      conditions. Despite the large abundance of disorder, disordered regions are still
      poorly detected. Recognition of disordered regions in a protein is instrumental
      for reducing spurious sequence similarity between disordered regions and ordered
      ones, and for delineating boundaries of protein domains amenable to
      crystallization. As presently none of the available automated methods for
      prediction of protein disorder can be taken as fully reliable on its own, we
      present a brief overview of the methods currently employed highlighting their
      philosophy. We show a few practical examples of how they can be combined to avoid
      pitfalls and to achieve more reliable predictions. We also describe the currently
      available methods for the identification of regions involved in induced folding
      and provide a few practical examples in which the accuracy of predictions was
      experimentally confirmed.

PMID- 17430196
TI  - Production and crystallization of protein domains: how useful are disorder
      predictions ?
AB  - The failure to produce and/or crystallize proteins is often due to their modular
      structure. There exists therefore considerable interest to develop strategies for
      tailoring proteins into crystallizable domains. In the framework of a Structural
      Genomics Project on soluble yeast proteins, we have tested the expression of
      numerous genetic constructs of our targets in order to produce and crystallize
      proteins and protein domains and solve their three-dimensional structure. In some
      cases, the choice of the domain boundaries was guided by prediction from sequence
      using various software packages, including Prelink, a home-made prediction method
      for detecting unfolded regions. In other cases, large numbers of constructs were
      generated using molecular biology or biochemical methods. In this paper, we
      analyze the results of the over-expression in E. coli and crystallization of
      these constructs, and compare these with the predictions that can be obtained
      from our software and from others.

PMID- 17430197
TI  - Prediction of protein disorder at the domain level.
AB  - Intrinsically disordered/unstructured proteins exist in a highly flexible
      conformational state largely devoid of secondary structural elements and tertiary
      contacts. Despite their lack of a well defined structure, these proteins often
      fulfill essential regulatory functions. The intrinsic lack of structure confers
      functional advantages on these proteins, allowing them to adopt multiple
      conformations and to bind to different binding partners. The structural
      flexibility of disordered regions hampers efforts solving structures at high
      resolution by X-ray crystallography and/or NMR. Removing such proteins/regions
      from high-throughput structural genomics pipelines would be of significant
      benefit in terms of cost and success rate. In this paper we outline the
      theoretical background of structural disorder, and review bioinformatic
      predictors that can be used to delineate regions most likely to be amenable for
      structure determination. The primary focus of our review is the interpretation of
      prediction results in a way that enables segmentation of proteins to separate
      ordered domains from disordered regions.

PMID- 17430198
TI  - Towards proteomic approaches for the identification of structural disorder.
AB  - Intrinsically unstructured/disordered proteins (IUPs) and protein domains lack a
      well-defined three-dimensional structure under physiological conditions.
      Structural disorder imparts advantages in many non-conventional functions, which
      poses a significant challenge to our understanding of the structure-function
      relationship of proteins. The general appreciation of this fact, however, is
      hampered by the large gap in our knowledge on IUPs, as we have biophysical data
      on less than 500 of them, whereas bioinformatic predictions suggest at least
      several thousand such proteins in the human proteome alone. Thus, proteomic-scale
      identification and characterization of IUPs will need to be implemented to fill
      this gap and advance our knowledge in this important field. In this review we
      give an insight into the various rationales of proteomic efforts of identifying
      IUPs, and survey the handful of attempts that combined enrichment of extracts for
      IUPs by heat- or acid treatment with a subsequent two-dimensional
      electrophoresis/mass spectrometry identification. Advantages and drawbacks of the
      various approaches are outlined in anticipation of future inventions in the field
      that will hopefully elevate IUP research to the truly proteomic level.

PMID- 17430199
TI  - Computer-assisted protein domain boundary prediction using the DomPred server.
AB  - Domain prediction from sequence is a particularly challenging task, and
      currently, a large variety of different methodologies are employed to tackle the
      task. Here we try to classify these diverse approaches into a number of broad
      categories. Completely automatic domain prediction from sequence alone is
      currently fraught with problems, but this should not be so surprising since human
      experts currently have significant disagreement on domain assignment even when
      given the structures. It can be argued that we should only test the domain
      prediction methods on benchmark data that human experts agree upon and this is
      the approach we take in this paper. Even for the data sets on which human experts
      agree, automatic structure-based domain assignment still cannot always agree, and
      so again it is still unlikely that domain prediction methods will reliably obtain
      correct results completely automatically. We make the argument that computer
      assisted domain prediction is a more achievable goal. With this aim in mind, we
      present the DomPred server. This server provides the user with the results from
      two completely different categories of method (DPS and DomSSEA). In this paper,
      each method is individually benchmarked against one of the latest domain
      prediction benchmarks to provide information about their respective
      reliabilities. A variety of different benchmark scores are employed since the
      accuracy of a domain prediction method depends critically on what types of
      results one wishes to obtain (single/multi-domain classification, domain number,
      residue linker positions, etc.). Also both of these methods, implemented within
      the DomPred server, can suggest alternative domain predictions, allowing the user
      to make the final decision based on these results and applying their own
      background knowledge to the problem. The DomPred server is available from the
      URL:http://bioinf.cs.ucl.ac.uk/software.html.

PMID- 17430200
TI  - Prediction of number and position of domain boundaries in multi-domain proteins
      by use of amino acid sequence alone.
AB  - Prediction of protein domain boundaries is an important step for the prediction
      of three-dimensional structure. The simple method PDP has been elaborated for
      prediction of the number and position of domain boundaries in multi-domain
      proteins by use of amino acid sequence alone. The method uses an optimized scale
      based on the statistics of appearance of amino acid residues at domain
      boundaries. Our method demonstrates promising results in comparison to other
      methods that do not use homologous sequences. From the database of proteins that
      are targets from CASP6 (Critical Assessment of Techniques for Protein Structure
      Prediction) our program correctly assigned the number of domains for
      approximately 80% of one domain proteins and approximately 50% for two-domain
      proteins. Our method offers three main advantages: it is very simple, it is fast,
      and it uses a minimal number of parameters in comparison with other methods.

PMID- 17430201
TI  - Posttranslational modifications and subcellular localization signals: indicators
      of sequence regions without inherent 3D structure?
AB  - Given the huge number of sequences of otherwise uncharacterized protein
      sequences, computer-aided prediction of posttranslational modifications (PTMs)
      and translocation signals from amino acid sequence becomes a necessity. We have
      contributed to this multi-faceted, worldwide effort with the development of
      predictors for GPI lipid anchor sites, for N-terminal N-myristoylation sites, for
      farnesyl and geranylgeranyl anchor attachment as well as for the PTS1 peroxisomal
      signal. Although the substrate protein sequence signals for various PTMs or
      translocation systems vary dramatically, we found that their principal
      architecture is similar for all the cases studied. Typically, a small stretch of
      the amino acid residues is buried in the catalytic cleft of the protein-modifying
      enzyme (or the binding site of the transporter). This piece most intensely
      interacts with the enzyme and its sequence variability is most restricted. This
      stretch is surrounded by linker segments that connect the part bound by the
      enzyme with the rest of the substrate protein. These residues are, as a trend,
      small with a flexible backbone and polar. Due to the mechanistic requirements of
      binding to the enzyme, we suggest that most PTM sites are necessarily embedded
      into intrinsically disordered regions (except for cases of autocatalytic PTMs,
      PTMs executed in the unfolded state or non-enzymatic PTMs) and this issue
      requires consideration in structural studies of proteins with complex
      architecture. Surprisingly, some proteins carry sequence signals for
      posttranslational modification or translocation that remain hidden in the normal
      biological context but can become fully functional in certain conditions.

PMID- 17430202
TI  - Pipelines, robots, crystals and biology: what use high throughput solving
      structures of challenging targets?
AB  - With recent advances in the technology and software underlying crystallographic
      structure solution, demands on both output and functional significance of X-ray
      structures are soaring. To achieve the required speed and quality also with ever
      larger and more difficult targets, combining HTP screening methods (robotics
      based or not) adopted from structural genomics initiatives with thorough
      expertise and dedicated characterization effort for each individual target is
      almost a must. I present concepts, practical considerations, and experiences on
      implementing an HTP technology platform for structural and functional studies on
      complexes, membrane proteins and other challenging targets. Emphasis lies on the
      environment of small academic groups engaged exclusively in hypothesis driven
      projects focused on specific biological systems. Suitability of given HTP
      protocols for particular target classes, benchmarking and quality control for
      procedures, and project management issues at the interface between extensive,
      broad parameter screening and intensive individual target work required by non-SG
      amenable targets are discussed.

PMID- 17430205
TI  - 2'-Modified oligonucleotides for antisense therapeutics.
AB  - Chemically modified antisense oligonucleotides are currently progressing in
      multiple clinical trials. Among several chemical modifications made, modification
      of the 2'-position has proved most successful. Second generation antisense
      oligonucleotides incorporating these 2'-modifications exhibit high binding
      affinity to target RNA, enhanced metabolic stability, and improved
      pharmacokinetic and toxicity profiles. This is, in part, due to the enhanced
      biophysical properties of second generation antisense oligonucleotides. 2'
      Modifications that influence the sugar to adopt a 3'-endo sugar pucker can
      improve properties such as affinity. 2'-Modifications that provide a gauche
      effect and/or a charge effect can play a significant role in the level of
      nuclease resistance. The heterocyclic base modifications such as 2-thiothymine
      provides additive effect on the affinity of 2'-F and 2'-O-MOE modifications. This
      review summarizes the structural and biophysical properties of selected 2'
      modified nucleosides which are candidates for use in oligonucleotide
      therapeutics.

PMID- 17430206
TI  - Morpholino, siRNA, and S-DNA compared: impact of structure and mechanism of
      action on off-target effects and sequence specificity.
AB  - Generally a gene knockdown agent should achieve high sequence specificity and
      should lack off-target effects (non-antisense effects due to interactions with
      structures other than gene transcripts). Three major gene knockdown types are
      compared with respect to off-target effects and sequence specificities: 1)
      phosphorothioate-linked DNA (S-DNA); 2) short interfering RNA (siRNA); and, 3)
      Morpholino. S-DNAs cause multiple off-target effects, largely because their
      backbone sulfurs bind to many different proteins. S-DNAs also achieve poor
      sequence specificity because S-DNA/RNA duplexes as short as 7 base-pairs are
      cleaved by RNase H. siRNAs cause several off-target effects, but improved designs
      may soon avoid such effects. siRNAs also provide only limited sequence
      specificity because their short guide sequences largely determine which gene
      transcripts will be blocked or cleaved, and those guide sequences appear to
      recognize insufficient sequence information to uniquely target a selected gene
      transcript. This specificity limitation is inherent in their mechanism of action
      and so probably cannot be greatly improved. Morpholinos are virtually free of off
      target effects--probably because they cannot interact electrostatically with
      proteins. Morpholinos also achieve exquisite sequence specificity--in large part
      because they must bind at least about 14 to 15 contiguous bases to block a gene
      transcript, and this constitutes sufficient sequence information to uniquely
      target a selected gene transcript. Because of their freedom from off-target
      effects, exquisite sequence specificity, complete stability in biological
      systems, and highly predictable targeting, Morpholinos dominate the most
      demanding of all gene knockdown applications, studies in developing embryos.

PMID- 17430208
TI  - Nucleobase modifications in peptide nucleic acids.
AB  - Peptide nucleic acid (PNA) is an oligonucleotide mimic originally designed upon a
      repeating N-(2-aminoethyl)glycine polyamide backbone to which nucleobase
      heterocycles are attached through a methylene carbonyl linkage to the alpha-amino
      group. These molecules possess remarkable hybridization properties with DNA or
      RNA forming complexes with high stability and with excellent sequence
      discrimination despite the substantial structural divergence from natural nucleic
      acids. Since the disclosure of PNA, a vibrant research community with interest in
      the chemistry and applications of polyamide-based nucleic acid analogs has
      developed. This has led to the synthesis and evaluation of a wide variety of
      modified polyamide nucleic acids. The focus of this report is a comprehensive
      review of nucleobase modifications in aminoethylglycine (aeg) PNA with reference,
      where appropriate, to the same modification in DNA or RNA.

PMID- 17430207
TI  - True antisense oligonucleotides with modified nucleotides restricted in the N
      conformation.
AB  - As first-generation antisense oligonucleotides, more than a dozen
      phosphorothioate oligodeoxynucleotides (PS ODNs) have been clinically developed,
      but only one has reached the market. To improve the drawbacks of PS ODNs, such as
      low affinity to target mRNA and non-specific binding to proteins, modified
      oligonucleotides with 2'-modified sugars such as 2'-O-(2-methoxy)ethyl and 2'-F
      modification or with bridged sugars such as oxyalkylene linkages between 2'
      oxygen and 4'-carbon, have been synthesized as 2'-MOE, 2'-F RNA, 2',4'-BNA/LNA
      and ENA oligonucleotides. They have shown properties of higher affinity to
      complementary single-stranded RNA and DNA than those of PS ODNs due to their
      preorganized N-conformation. On the basis of the properties of these newly
      designed oligonucleotides, their in vitro and in vivo applications for gene
      silencing as true antisense oligonucleotides have been reported. In this review,
      antisense applications with these modified oligonucleotides are focused on.

PMID- 17430209
TI  - Peptide nucleic acids with a structurally biased backbone: effects of
      conformational constraints and stereochemistry.
AB  - Peptide nucleic acids (PNAs) are polyamidic oligonucleotide analogs which have
      been described for the first time fifteen years ago and were immediately found to
      be excellent tools in binding DNA and RNA for diagnostics and gene regulation.
      Their use as therapeutic agents have been proposed since early studies and recent
      advancements in cellular delivery systems, and in the so called anti-gene
      strategy, makes them good candidates for drug development. The search for new
      chemical modification of PNAs is a very active field of research and new
      structures are continuously proposed. This review focuses on the recent
      advancements obtained by the modification of the PNA backbone, and their possible
      use in medicinal chemistry. In particular two classes of structurally biased PNAs
      are described in details: i) PNAs with acyclic structures and their helical
      preference, which is regulated by stereochemistry and ii) cyclic PNAs with
      preorganized structures, whose performances depend both on stereochemistry and on
      conformational constraints. The properties of these compounds are discussed in
      terms of affinity for nucleic acids, and several recent examples of their use in
      cellular or animal systems are presented.

PMID- 17430210
TI  - P-chiral oligonucleotides in biological recognition processes.
AB  - Internucleotide phosphodiester linkages in non-modified oligonucleotides are
      quickly degraded by nucleolytic enzymes present in the cells and this feature
      practically eliminates natural DNA and RNA molecules from medical applications
      and from many structural and mechanistic studies. P-chiral oligonucleotide
      analogs, in which one of the non-bridging phosphate oxygen atoms is substituted
      with another heteroatom (e.g. S, Se) or a chemical group (e.g. CH3, BH3(-)), have
      significantly greater nuclease resistance and also offer important possibilities
      for detailed studies of interactions with other biomolecules at the molecular
      level. Notably, these substitutions do not disrupt hydrogen bonding between
      nucleobases and affect the overall geometry of the oligomers to only low or
      moderate extent, although important changes of hydration patterns and changes of
      interactions with metal ions are observed. Such the probes, including
      isotopomeric species labeled with a heavy oxygen isotope, possessing phosphorus
      atoms of selected absolute configurations, have been used for elucidation of the
      mode of action of many enzymes (nucleases, transferases, kinases), ribozymes and
      DNA-zymes, as well as for investigations on thermodynamic stability of nucleic
      acids complexes (duplexes, triplexes, i-motif) and for studies on a mechanism of
      conformational changes of B-Z type. They are also useful tools for analysis of
      interactions of the phosphoryl oxygen atoms in natural precursors with functional
      groups of proteins. The synthetic routes to stereodefined forms of selected types
      of P-chiral oligonucleotides are presented, as well as recently developed methods
      for their configurational analysis at micromolar concentration. Selected examples
      of application of diastereomerically pure P-chiral oligonucleotides for
      structural, biochemical and biological experiments are discussed.

PMID- 17430211
TI  - Structure-editing of nucleic acids for selective targeting of RNA.
AB  - The synthesis of backbone-modified nucleic acids has been an area of very intense
      research over the last two decades. The main reason for this research activity is
      the instability of nucleic acid based drugs in the intracellular conditions.
      Changes in the sugar-phosphate backbone invariably bring about the changes in the
      complementation properties of the nucleic acids. The naturally occurring
      deoxyribose- (DNA) and ribose (RNA) sugar-phosphate backbones are endowed with
      considerable differences in their binding affinities towards themselves. This
      occurs because of the different sugar conformations prevalent in DNA and RNA and
      the subtle structural changes accruing from these in hydrogen bonding, base
      stacking interactions and hydration of major/minor grooves. The six-atom
      phosphodiester linkages and pentose-sugars give immense opportunities for
      chemical modifications that lead to several backbone-modified nucleic acid
      structures. This article is focused on such modifications that impart RNA
      selective binding properties to the modified nucleic acid mimics and the
      rationale behind the said selectivity. It is found that the six-atom sugar
      phosphate backbone could be replaced by either one-atom extended or one-atom
      edited repeating units, leading to the folded or extended geometries to maintain
      the internucleoside distance-complementarity. Other important contributions come
      from electronegativity of the substituent groups, hydration in the major/minor
      groove, base stacking etc.

PMID- 17430212
TI  - Chemical modifications to improve the cellular uptake of oligonucleotides.
AB  - Specific control of gene expression by synthetic oligonucleotides (ON) is now
      widely used for target validation but clinical applications are limited by ON
      bioavailability. Moreover, most currently used strategies for physical and
      chemical delivery cannot be easily implemented in vivo. This article reviews new
      strategies which appear promising for ON delivery. The first part deals with ON
      chemical modifications aiming at improving cellular uptake as for instance the
      grafting of cationic groups on the ON backbone. The second part concerns ON
      conjugation to cell penetrating peptides.

PMID- 17430213
TI  - Inflammation, sleep, obesity and cardiovascular disease.
AB  - Evidence is emerging that disturbances in sleep and sleep disorders play a role
      in the morbidity of chronic conditions. However, the relationship between sleep
      processes, disease development, disease progression and disease management is
      often unclear or understudied. Numerous common medical conditions can have an
      affect on sleep. For example, diabetes or inflammatory conditions such as
      arthritis can lead to poor sleep quality and induce symptoms of excessive daytime
      sleepiness and fatigue. It has also been suggested that poor sleep may lead to
      the development of cardiovascular disease for which an underlying inflammatory
      component has been proposed. It is therefore important that the development and
      progression of such disease states are studied to determine whether the sleep
      effect merely reflects disease progression or whether it may be in some way
      causally related. Sleep loss can also have consequences on safety related
      behaviours both for the individuals and for the society, for example the
      increased risk of accidents when driving while drowsy. Sleep is a complex
      phenotype and as such it is possible that there are numerous genes which may each
      have a number of effects that control an individual's sleep pattern. This review
      examines the interaction between sleep (both quantity and quality) and parameters
      of cardiovascular risk. We also explore the hypothesis that inflammation plays an
      essential role in cardiovascular disease and that a lack of sleep may play a key
      role in this inflammatory process. AIM: To review current evidence regarding the
      endocrine, metabolic, cardiovascular and immune functions and their interactions
      with regard to sleep, given the current evidence that sleep disturbances may
      affect each of these areas.

PMID- 17430214
TI  - Bone marrow stem cell therapy for myocardial angiogenesis.
AB  - Despite the recent advances in medical therapy and coronary revascularization
      procedures, coronary artery disease (CAD) remains the major cause of morbidity
      and mortality in the developing countries. In patients with severe CAD,
      persistent myocardial ischemia in hibernated myocardium resulted in progressive
      loss of cardiomyocytes with development of heart failure. As a result,
      therapeutic approaches to enhance neovascularization are being underwent
      intensive investigation. Recent experimental studies have demonstrated adult bone
      marrow (BM) can induce neovascularization in ischemic myocardium can improve
      heart function. These findings have prompted the development of different
      cellular transplantation approaches for heart diseases refractory to conventional
      therapy after myocardial infarction. Although the initial pilot clinical trials
      have shown potential clinical benefit of BM therapy for therapeutic angiogenesis,
      the long-term safety, the optimal timing and treatment strategy remains unclear.
      Furthermore, in order to acquire more optimized quality and quantity of BM
      derived stem cell for myocardial regeneration, several issues remain to be
      addressed, such as the development of a more efficient method of stem cells
      identification, purification and expansion. Emerging, rationally designed,
      randomized clinical trials are required to assess the clinical implication of BM
      derived stem cells therapy in treatment of CAD.

PMID- 17430215
TI  - Vascular wall shear stress in clinical practice.
AB  - Wall shear stress is a fluid dynamic quantity that is gradually emerging as a
      potentially important factor of coronary atherosclerosis. Methods, therefore, of
      estimation of shear stress in the arterial system are of clinical relevance. The
      purpose of this review is to define wall shear stress, review the various methods
      that have been used for its assessment in human circulation, and examine the
      methodological limitations and applicability of each method in clinical practice.

PMID- 17430216
TI  - Antagonists of activated factor X and thrombin: innovative antithrombotic agents.
AB  - Anticoagulant drugs are traditionally administered for the prevention and
      treatment of thrombosis. Besides multi-targeted, traditional anticoagulants, such
      as coumarins or heparins, the search for the optimal antithrombotic efficacy to
      bleeding risk ratio has prompted the development of a novel armamentarium of
      anticoagulant drugs, which is expected to be introduced in the market. These
      emerging drugs are mainly targeted to suppress the propagation of the coagulation
      cascade (thrombin burst), by direct thrombin inhibition or selective inhibition
      of activated factor X. Therefore, thrombin or activated factor X antagonists
      would produce an efficient anticoagulation while minimizing the risk of bleeding,
      the most common adverse events of conventional anticoagulants. No routine
      monitoring, favorable form of administration and better compliance are additional
      advantages of these innovative drugs, which are already in advanced development
      or already licensed for clinical use. The aim of this article is to provide an
      overview on the mechanisms of action, clinical applications, cost-effectiveness
      and side effects of these emerging anticoagulant strategies.

PMID- 17430217
TI  - Drug-induced pulmonary hypertension in newborns: a review.
AB  - Persistent pulmonary hypertension (PPHN) is a disease characterised by the
      disruption of the transition from fetal to neonatal circulation with the
      persistence of high pulmonary vascular resistances and right-to left shunting.
      This condition, occurring in about 1-2 newborns per 1000 live births, causes
      severe hypoxemia. Despite significant improvements in treatment, the mortality of
      PPHN varies from 10 to 20 % of affected newborns. Pulmonary hypertension is
      frequently observed in some cardiac malformation and in congenital diaphragmatic
      hernia, in meconium aspiration syndrome, neonatal sepsis, podalic presentation
      and male sex. Maternal risk factors are tobacco smoking, cesarean section, low
      socio-economic conditions, diabetes and urinary infections. Another predisposing
      condition is antenatal or postnatal exposure to some drugs. The medications
      involved in drug-induced pulmonary hypertension and the mechanisms involved are
      reviewed.

PMID- 17430218
TI  - Significance of aspirin and clopidogrel resistance in patients undergoing
      percutaneous coronary interventions.
AB  - Dual antiplatelet therapy (aspirin plus clopidogrel) is mandatory in patients
      treated with coronary stent implantation. This strategy is highly effective in
      prevention of stent thrombosis until its struts are covered with endothelium.
      However, a substantial number of patients still suffer from recurrent ischemic
      coronary events despite adequate antiplatelet therapy. These events fall into
      three categories: stent thrombosis, in stent restenosis and events related to
      other non-stented coronary lesions. Some data suggest that beside other local and
      systemic factors resistance to aspirin and clopidogrel may be a possible cause of
      stent thrombosis and ischemic events in patients after coronary interventions.
      Several mechanisms of antiplatelet drug resistance have been reported including
      poor compliance, interactions with other drugs, genetic polymorphism or increased
      platelet turnover. More research is needed to adequately assess the clinical
      significance and prognostic value of antiplatelet drug resistance detected by
      laboratory tests in patients undergoing percutaneous intervention. We review
      published data on mechanisms and the clinical significance of aspirin and
      clopidogrel resistance in patients after coronary interventions.

PMID- 17430219
TI  - Therapeutic potential for thyroid hormone receptor-beta selective agonists for
      treating obesity, hyperlipidemia and diabetes.
AB  - Obesity and metabolic syndrome are increasing dramatically worldwide,
      contributing to cardiovascular morbidity and mortality. There are currently few
      safe and efficacious therapeutics for obesity and most strategies are focused on
      appetite suppression. Thyroid hormones reduce adiposity via increased metabolic
      rate, but unfortunately they cause large changes in metabolic rate and direct
      cardiac acceleration, making them useless for treating obesity. Thyroid hormone
      receptors (TRs) work as transcription factors and two subtypes exist: TRalpha and
      TRbeta. TRalpha mediates tachycardia and much of the metabolic rate effect, while
      TRbeta mediates cholesterol and TSH lowering effects of thyroid hormones. TRbeta
      activation modestly increases metabolic rate such that a therapeutic window of 5
      10 fold increases in metabolic rate can be seen without tachycardia. This was
      initially studied in TRalpha(1)(-/-) mice. Recent structure activity work has
      resulted in the discovery of several TRbeta selective thyromimetics such as KB
      141. Studies with KB-141 show that it has a 10-fold window in which therapeutic
      increases in metabolic rate are seen without tachycardia or cardiac hypertrophy.
      This agent lowers cholesterol in rats and primates. In primates, KB-141 causes
      significant weight and cholesterol reduction in addition to the independent risk
      factor Lp(a). These effects were seen without any effect on heart rate, unlike
      thyroid hormone (T(3)). Further work with TRbeta selective agents is warranted
      and recent work suggests the possibility of developing compounds that selectively
      penetrate different tissues which may have an even more desirable therapeutic
      window. Selective thyromimetics, therefore, may be useful as adjunctive therapy
      to appetite suppressants along with exercise and diet restriction.

PMID- 17430220
TI  - Effects of statins on blood pressure: a review of the experimental and clinical
      evidence.
AB  - The "pleiotropic" effects of statins have been the centre of a considerable
      research activity. Among the numerous experimental and clinical studies of this
      field, some focused on the effects of statins on blood pressure (BP), while
      others reported data on BP together with other parameters. Some of the animal or
      human studies do not show an association between statin treatment and BP changes,
      whereas others usually report mild but significant reductions. Among the latter,
      all clinical studies using ambulatory BP recordings show a significant drop in
      both systolic and diastolic BP in hypertensive patients. In addition,
      accumulating evidence has identified a number of statin actions that may be
      involved in BP lowering. Overall, current evidence suggests that statins can be
      associated with a mild beneficial effect on BP, but further research is needed to
      clarify the exact magnitude of this action, as well as its clinical relevance.

PMID- 17430221
TI  - Cardiovascular effects of omega-3 free Fatty acids.
AB  - Omega-3 fatty acids are essential substances for the development and function of
      human organism. They cannot be synthesized in humans, and consequently have to be
      acquired from food, almost exclusively from fish. Omega-3 fatty acids exert
      potent anti-inflammatory and anti-atherosclerotic actions by interfering with the
      metabolism of arachidonic acid, modifying lipid composition (mainly lowering
      triglycerides), improving hemodynamics and reducing cardiac hypertrophy.
      Recently, clinical and experimental studies demonstrated an anti-arrhythmic
      effect and a significant impact on survival after myocardial infarction (MI). It
      follows that omega-3 fatty acids have been widely accepted for clinical use in
      patients with dyslipidemia or with atherosclerotic disease and in survivors of
      acute MI. This review briefly explores the metabolic mechanisms and the clinical
      effects of this class of substances and considers their use in patients with
      cardiovascular disease.

PMID- 17430222
TI  - Microwave assisted medicinal chemistry.
AB  - Microwave irradiation has been used to enhance organic reactions since the mid
      80's, its use within the field of medicinal chemistry is not so widely evident in
      the literature. The present review highlights the use of microwave chemistry as
      an important tool for the fast development of structure activity relationship in
      several programs related to various therapeutic areas.

PMID- 17430223
TI  - Pharmacological modulation of sphingolipids and role in disease and cancer cell
      biology.
AB  - Sphingolipids comprise a family of bioactive lipids that exert antagonizing roles
      in diverse cellular functions such as cell proliferation, growth arrest or
      apoptosis. Synthesized in the ER/Golgi, sphingolipids are subsequently
      distributed to different compartments, most predominantly in the plasma membrane,
      where they integrate signaling platforms. In addition to its precursor role in
      the synthesis of complex glycosphingolipids, ceramide has been identified as a
      cell death effector and its generation increases in response to apoptotic stimuli
      including stress, radiation, chemotherapy, and death ligands. In contrast,
      sphingosine-1-phosphate (S1P) has been mainly characterized as an antiapoptotic
      sphingolipid mediating cell proliferation and survival. Thus, the relative
      balance between ceramide and SIP has important implications in disease
      pathogenesis, and therefore the pharmacological modulation of enzymes involved in
      regulation of the ceramide to SIP ratio could constitute a novel therapeutic
      approach for the treatment of human diseases and cancer.

PMID- 17430224
TI  - Fondaparinux: pharmacology and clinical experience in cardiovascular medicine.
AB  - Fondaparinux is a synthetic, five-saccharide chain, AT-dependent, anti-FXa agent.
      Studies showed that fondaparinux acts in prevention and treatment of venous
      thromboembolism and in ischemic heart disease, without significant bleeding risk.
      The drug inhibits thrombin generation, has long half-life and can be administered
      once-daily without laboratory monitoring. It may be used in HIT treatment.

PMID- 17430225
TI  - The contribution of oxazolidinone frame to the biological activity of
      pharmaceutical drugs and natural products.
AB  - The development of resistance by the antibiotics in the Gram-positive pathogenic
      bacteria over the last twenty years and continuing today has created a need for
      new antibiotic classes, which may be unaffected by existing bacterial resistance.
      The oxazolidin-2-ones represent not only a new class with a novel mechanism of
      action, but also satisfy the requirement for overcoming the resistance
      mechanisms. Both linezolid and eperozolid, the first chemical candidates, arose
      from the piperazine subclass, with the first one being chosen further development
      because of its enhanced pharmacokinetic properties. The main attractive traits of
      the oxazolidinone series has encouraged further work in the area, and the patent
      literature reveals that extensive chemical investigation is currently being made.
      The unexpected early resistance development emphasizes the need for further
      exploration of features of the oxazolidinone to eliminate these deficiencies.
      Recently, several changes, involving the C5 side chain as well the N-phenyl
      heterocyclic ring, give promise for such improvement. Oxazolidinone antibacterial
      agents comprise also ketolides, derivatives of macrolides, such as erythromycin
      A, with a newly formed carbamate cycle, with a largely unexplored potential. The
      oxazolidinone nucleus does not appear only in the structures of antimicrobial
      drugs, but a number of biological activities are connected with frameworks
      including the oxazolidinone ring. A partial list of these activities comprises
      enzyme inhibitors, agonists and antagonists, with a particular citation for a new
      generation of selective monoamino oxidase inhibitors (befloxatone). The
      oxazolidinone moiety was found in the structure of few biologically active
      natural products, such as (-)-cytoxazone and streptazolin. Moreover, in some
      cases the oxazolidinone ring has been chosen for the preparation of isosteric aza
      analogues of natural compounds (podophyllotoxin, pilocarpine) that can be more
      easily synthesised and more hardly inactivated. Finally, the participation of
      oxazolidinone chiral auxiliaries to several syntheses of natural products must be
      acknowledged.

PMID- 17430226
TI  - Artemisinin, promising lead natural product for various drug developments.
AB  - Artemisinin and its synthetic derivatives are widely used for antimalarial agents
      in the world. Moreover, they are discovered to additionally use as anticancer,
      antiangiogenesis, antiviral, immunosuppressive, and antifungal agents. Recent
      research results supported that it is a very promising field in drug discovery.
      In this review, it will discuss the structural and biological features of
      artemisinin and its derivatives that have published since 2003 except
      antimalarial, and show that they are useful lead compounds for novel drug
      discovery.

PMID- 17430228
TI  - Synthetic approaches to the 2005 new drugs.
AB  - New drugs are introduced to the market every year and each individual drug
      represents a privileged structure for its biological target. In addition, these
      new chemical entities (NCEs) not only provide insights into molecular
      recognition, but also serve as drug-like leads for designing future new drugs. To
      these ends, this review covers the syntheses of 22 NCEs marketed in 2005.

PMID- 17430227
TI  - Involvement of dendritic cells in allograft rejection new implications of
      dendritic cell-endothelial cell interactions.
AB  - For almost half a century immunologists have tried to tear down the MHC barrier,
      which separates two unrelated individuals during transplantation. Latest
      experimental data suggest that a breakthrough in vitro is imminent. Dendritic
      cells (DCs), which activate naive allo-reactive T-cells (TCs), play a central
      role in the establishment of allo-antigen-specific immunity. Allograft solid
      organ rejection is initiated at the foreign endothelial cell (EC) layer, which
      forms an immunogenic barrier for migrating DCs. Thus, DC/EC interactions might
      play a crucial role in antigen-specific allograft rejection. Organ rejection is
      mediated by host allo-reactive TCs, which are activated by donor DCs (direct
      activation) or host DCs (indirect activation). Direct allo-antigen presentation
      by regulatory dendritic cells (DCreg) can play an instructive role towards
      tolerance induction. Several groups established that, DCregs, if transplanted
      beforehand, enter host thymus, spleen, or bone marrow where they might eventually
      establish allo-antigen-specific tolerance. A fundamental aspect of DC function is
      migration throughout the entire organism. After solid organ transplantation, host
      DCs bind to ECs, invade allograft tissues, and finally transmigrate into lymphoid
      vessels and secondary lymphoid organs, where they present allo-antigens to naive
      host TCs. Recent data suggest that in vitro manipulated DCregs may mediate allo
      transplantation tolerance induction. However, the fundamental mechanisms on how
      such DCregs cause host TCs in the periphery towards tolerance remain unclear. One
      very promising experimental concept is the simultaneous manipulation of DC direct
      and indirect TC activation/suppression, towards donor antigen-specific allo
      transplantation tolerance. The allo-antigen-specific long-term tolerance
      induction mediated by DCreg pre-transplantation (with simultaneous short-term
      immunosuppression) has become reproducible in the laboratory animal setting.
      Despite the shortcomings of laboratory animal studies, strong promises are
      deriving from these studies for clinical kidney, heart, and liver
      transplantation.

PMID- 17430229
TI  - Exploring the links between obesity and Alzheimer's disease.

PMID- 17430230
TI  - An introduction to obesity and dementia.
AB  - The increasing prevalence of obesity world-wide has an expected consequent
      increase in diabetes and cardiovascular disease. Less attention has been paid to
      the effect of obesity on dementia. This overview discusses methodological issues
      related to the epidemiologic study of obesity and dementia, reviews results of
      long-term prospective studies, and briefly considers possible mechanisms for an
      obesity-dementia association. At least six cohort studies of 18 to 32 years
      duration confirm that overweight middle-aged or older adults are at increased
      risk of dementia in later life. In many of these studies, the association
      persisted after adjusting for classical cardiovascular risk factors. A few
      epidemiologic studies (and more laboratory studies not reviewed here) suggest
      biomarkers such as C-reactive protein, interleukin 6, and leptin may explain part
      of the obesity-dementia connection. If any of these factors are in the causal
      pathway to dementia, their reversal or prevention by weight control would have
      huge public health importance.

PMID- 17430231
TI  - Body mass index in midlife and risk of Alzheimer disease and vascular dementia.
AB  - Prior work has suggested that obesity and overweight as measured by body mass
      index (BMI) increases risk of dementia. It is unknown if there is a difference in
      the risk of developing Alzheimer disease (AD) versus vascular dementia (VaD)
      associated with high body weight. The goal of this study was to examine the
      association between midlife BMI and risk of both AD and VaD an average of 36
      years later in a large (N= 10,136) and diverse cohort of members of a health care
      delivery system. Participants aged 40-45 participated in health exams between
      1964 and 1968. AD and VaD diagnoses were obtained from Neurology visits between
      January 1, 1994 and June 15, 2006. Those with diagnoses of general dementia from
      primary care providers were excluded from the study. BMI was analyzed in WHO
      categories of underweight, overweight and obese, as well as in subdivisions of
      WHO categories. All models were fully adjusted for age, education, race, sex,
      marital status, smoking, hyperlipidemia, hypertension, diabetes, ischemic heart
      disease and stroke. Cox proportional hazard models showed that compared to those
      with a normal BMI (18.5-24.9), those obese (BMI > or = 30) at midlife had a 3.10
      fold increase in risk of AD (fully adjusted model, Hazard Ratio=3.10, 95% CI 2.19
      4.38), and a five fold increase in risk of VaD (fully adjusted model, HR=5.01,
      95% CI 2.98-8.43) while those overweight ( BMI > or = 25 and <30) had a two fold
      increase in risk of AD and VaD (fully adjusted model, HR=2.09, 95% CI 1.69-2.60
      for AD and HR=1.95, 95% CI 1.29-2.96 for VaD). These data suggest that midlife
      BMI is strongly predictive of both AD and VaD, independent of stroke,
      cardiovascular and diabetes co morbidities. Future studies need to unveil the
      mechanisms between adiposity and excess risk of AD and VaD.

PMID- 17430232
TI  - Relation of obesity to cognitive function: importance of central obesity and
      synergistic influence of concomitant hypertension. The Framingham Heart Study.
AB  - BACKGROUND: Obesity has been related to the incidence of dementia but its impact
      on cognitive performance in persons without dementia is less clear. We
      hypothesized that mid-life obesity may modulate the impact of conventional
      cardiovascular risk factors (CVRF) on cognitive impairment. We tested this
      hypothesis in the community-based Framingham Offspring Study sample. METHODS: At
      Examination cycle 4 (1988-90) of the Offspring Cohort, indices of obesity (BMI
      and Waist-Hip Ratio [WHR]) and baseline CVRF levels were ascertained in 1,814 men
      and women, aged 40-69 years. Obesity and hypertension were related to the score
      on each of 8 neurocognitive tests measured at Examination 8, 12 years later (1999
      2002). RESULTS: Midlife measures of central obesity (WHR in the uppermost
      quartile- Q4) and of hypertension (BP > or = 140 / > or = 90 or use of anti
      hypertensive medication) were each significantly related to poorer performance on
      executive function & visuomotor skills (Trails B, Visual Reproductions-Immediate
      and Delayed Recall). Further, the relation of hypertension to neurocognitive
      performance was significantly modified by WHR; hypertension was not associated
      with neurocognitive performance in WHR Q1-Q3, but was associated with a marked
      adverse performance in Q4 WHR. Neither HTN nor obesity was individually or
      synergistically related to verbal memory (immediate or delayed recall).
      CONCLUSIONS: Executive function and visuomotor skills were differentially
      affected by the combined presence of midlife hypertension and Q4 WHR while
      measures of verbal memory function were not related to these risk factors in our
      sample, a pattern consistent with vascular cognitive impairment. Control of mid
      life elevated blood pressure and central obesity may be strategies to reduce
      cognitive decline with age.

PMID- 17430233
TI  - The epidemiology of adiposity and dementia.
AB  - Adipose tissue is the largest endocrine gland in the body, yet only recently has
      its role in neurodegenerative disease been considered. Prospective population
      level evidence has emerged to show that both obesity and overweight, is
      associated with an increased risk of all cause dementia, Alzheimer's disease
      (AD), and underlying neurodegenerative changes. Weight loss in late life however
      is associated with dementia, and those categorized as underweight are also at a
      greater risk of dementia. Given the current epidemic of obesity, and the expected
      age-related increase in dementia incidence, even a small association between
      these two diseases has far reaching public health implications. However, due to
      the effects of both AD-associated weight loss and age-related changes in body
      composition, there are methodological challenges in appropriately evaluating
      obesity as a risk factor for developing dementia. There is a need to take a 'life
      course approach' and to consider the role of risk factors prior to the onset of
      old age. Our work has shown that both obesity and overweight, as measured by body
      mass index and skinfold thickness, in middle-age are strongly associated with an
      increased risk of all cause dementia, Alzheimer disease & Vascular dementia,
      independent of the development of diabetes and cardiovascular-related
      morbidities. There is also value in assessing regional body shape distributions
      of adiposity, particular the role of abdominal obesity. Mechanistic pathways such
      as adipocyte secreted proteins and hormones, and inflammatory cytokines could
      explain the association between obesity and increased risk of dementia.

PMID- 17430234
TI  - Metabolic syndrome and cognitive decline.
AB  - Over 33% of women and 20% of men aged 65 and older will develop dementia during
      their lifetime, and many more will develop a milder form of cognitive impairment.
      Given the anticipated exponential increase in both the incidence and prevalence
      of cognitive impairment in the next century, it is critical to identify
      preventative strategies to thwart this critical public health issue. The
      metabolic syndrome is comprised of five cardiovascular risk factors that include
      abdominal obesity, hypertriglyceridemia, low high density lipoprotein (HDL)
      levels, hypertension, and hyperglycemia. The prevalence of the metabolic
      syndrome, similar to that for cognitive disorders, increases dramatically with
      age. While several of the individual components of the metabolic syndrome have
      been linked to risk of developing dementia and cognitive impairment, few studies
      have looked at the components of the metabolic syndrome as a whole. We found, in
      two separate studies involving elders of different ethnicities, that the
      metabolic syndrome is a risk factor for accelerated cognitive aging. This was
      especially true for elders with the metabolic syndrome and with elevated serum
      level of inflammation. Several possible mechanisms may explain the association
      between the metabolic syndrome and cognitive decline including micro- and macro
      vascular disease, inflammation, adiposity and insulin resistance. If metabolic
      syndrome is associated with increased risk of developing cognitive impairment,
      regardless of mechanism, then early identification and treatment of these
      individuals might offer avenues for disease course modification.

PMID- 17430236
TI  - What can imaging reveal about obesity and the brain?
AB  - Brain imaging has played a major role in exploring abnormalities of brain
      structure and function in aging and dementia. Recently, with reports linking
      obesity to cognitive decline and dementia, magnetic resonance imaging has been
      used to investigate how brain structure may be altered with obesity. These
      studies have convincingly demonstrated both generalized and regional brain
      atrophy and changes in white matter in association with obesity. These results do
      not appear to be simply explained by links to cardiovascular disease. However,
      the mechanisms underlying these alterations are unclear and could be accounted
      for by a number of different processes that are known to alter brain structure
      and which could also be related to obesity. Application of additional imaging
      methods could help to establish the pathway through which obesity produces
      cognitive decline and dementia.

PMID- 17430237
TI  - Next steps in Alzheimer's disease research: interaction between epidemiology and
      basic science.
AB  - Epidemiologic studies have provided important clues about the etiology, prognosis
      and options for prevention and treatment of AD, and sub-clinical changes in
      cognition and brain structure. A brief review is given of what we have learned
      from epidemiologic studies of risk factors and natural history. This is followed
      by a discussion of how these findings could inform the design of basic research
      strategies that may further the translation of bench science to the clinic and
      public health arena.

PMID- 17430235
TI  - Adiposity and Alzheimer's disease.
AB  - The objective of this manuscript is to provide a comprehensive review of the
      relation between adiposity and Alzheimer's disease (AD), its potential
      mechanisms, and issues in its study. Adiposity represents the body fat tissue
      content. When the degree of adiposity increases it can be defined as being
      overweight or obese by measures such as the body mass index. Being overweight or
      obese is a cause of hyperinsulinemia and diabetes, both of which are risk factors
      for AD. However, the epidemiologic evidence linking the degree of adiposity and
      AD is conflicting. Traditional adiposity measures such as body mass index have
      decreased validity in the elderly. Increased adiposity in early or middle adult
      life leads to hyperinsulinemia which may lead to diabetes later in life. Thus,
      the timing of ascertainment of adiposity and its related factors is critical in
      understanding how it might fit into the pathogenesis of AD. We believe that the
      most plausible mechanism relating adiposity to AD is hyperinsulinemia, but it is
      unclear whether specific products of adipose tissue also have a role. Being
      overweight or obese is increasing in children and adults, thus understanding the
      association between adiposity and AD has important public health implications.

PMID- 17430238
TI  - Animal models of obesity and metabolic syndrome: potential tools for Alzheimer's
      disease research.
AB  - Emerging evidence suggests that components of the metabolic syndrome either in
      isolation or in aggregate may impact the onset or severity of neurodegenerative
      processes, including those physiologic changes that lead to Alzheimer's Disease
      (AD). Several animal models that were originally designed to interrogate the
      metabolic syndrome are readily available. These models can now be used to support
      studies that may provide new mechanistic links between the metabolic syndrome and
      neurodegeneration. In addition, animal strains currently being generated and
      phenotyped through the efforts of an array of NIDDK-supported projects are likely
      to provide novel and better tools to advance Alzheimer's disease research in the
      near future.

PMID- 17430239
TI  - Insulin resistance and Alzheimer's disease pathogenesis: potential mechanisms and
      implications for treatment.
AB  - Insulin modulates cognition and other aspects of normal brain function. Insulin
      resistance is characterized by chronic peripheral insulin elevations, and it is
      accompanied by reduced brain insulin levels and insulin activity. Obesity, type 2
      diabetes mellitus and hypertension are strongly associated with insulin
      resistance. In addition, insulin resistance increases the risk of age-related
      memory impairment and Alzheimer's disease. Possible mechanisms through which
      these risks are increased include the effects of peripheral hyperinsulinemia on
      memory, CNS inflammation, and regulation of the beta-amyloid peptide. We have
      shown that raising plasma insulin in humans to levels that characterize patients
      with insulin resistance increases the levels of Abeta and inflammatory agents in
      brain. These convergent effects may impair memory and induce AD pathology.
      Therapeutic strategies focused on preventing or correcting insulin abnormalities
      may thus benefit a subset of adults with age-related memory impairment and AD.

PMID- 17430240
TI  - Insulin resistance, glycemic control and adiposity: key determinants of healthy
      lifespan.
AB  - Identification of genes and pathways that alter lifespan has allowed for new
      insights into factors that control the aging process as well as disease. While
      strong molecular links exist between aging and metabolism, we hypothesize that
      targeting the mechanisms involved in aging will also give rise to therapeutics
      that treat other devastating age-related diseases, such as neurodegeneration,
      cancer, inflammation and cardiovascular disease. Insulin sensitivity, glycemic
      control and adiposity are not only hallmarks of the major metabolic diseases,
      type 2 diabetes and obesity, but they also represent significant risk factors for
      the development of Alzheimer's Disease and cognitive impairment. Insulin/IGF-1
      signaling is an important pathway regulating aging and disease in a variety of
      species, including mammals. Here we describe an important role for the gut
      derived peptide ghrelin in upstream signaling through the insulin/IGF-1 pathway
      and exemplify modulation of ghrelin signaling as an approach to mechanistic
      treatment of multiple age-related diseases by virtue of its ability to regulate
      key metabolic functions.

PMID- 17430241
TI  - Therapeutic use of agonists of the nuclear receptor PPARgamma in Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disease for which
      there are no highly effective therapies. A novel therapeutic approach to the
      treatment of AD is the use of agonists of the nuclear receptor, peroxisome
      proliferators-activated receptor gamma (PPARgamma). PPARgamma is a ligand
      activated transcription factor whose best described roles are to regulate lipid
      metabolism and inflammation. Agonists of PPARgamma have been shown to ameliorate
      AD-related pathology in animal models of AD and improve cognition. A number of
      potential mechanisms have been advanced to account for these effects. PPARgamma
      agonists act as insulin sensitizers, facilitating insulin action. In addition,
      PPARgamma agonists have been shown to inhibit inflammatory gene expression, alter
      Abeta homeostasis and exhibit neuroprotective effects. Importantly, recent
      clinical trials of FDA approved PPARgamma agonists have been shown to improve
      cognition and memory in AD patients. Thus, PPARgamma agonists represent a new and
      potentially efficacious treatment of AD.

PMID- 17430242
TI  - Cholesterol metabolism and brain amyloidosis: evidence for a role of copper in
      the clearance of Abeta through the liver.
AB  - Mounting evidence suggests that copper may influence the progression of
      Alzheimer's disease by reducing clearance of the amyloid beta protein (Ass) from
      the brain. We propose that Abeta is cleared from the brain by tagging along with
      cholesterol/ApoE in traversing the BBB, with subsequent incorporation into HDL
      for delivery of the toxin to the liver. It is suggested that either ABC-A1 or
      LRP, or both are involved in Abeta transport across the BBB, as well as normal
      cholesterol efflux. We have previously shown that addition of only 0.12 PPM
      copper (one-tenth the Environmental Protection Agency Human consumption limits)
      to distilled water was sufficient to precipitate the accumulation of Ass in the
      brains of cholesterol-fed rabbits. Here we show that in a setting of elevated
      cholesterol levels, overproduced Abeta is cleared to the blood and can
      simultaneously be identified in the liver if copper ion is absent from the
      animal's drinking water, but if trace levels copper (0.12 PPM) are added to the
      drinking water Abeta accumulates in the brain, while the levels in the liver are
      greatly reduced.

PMID- 17430243
TI  - Role of LXR and ABCA1 in the pathogenesis of Alzheimer's disease - implications
      for a new therapeutic approach.
AB  - Studies, ranging from epidemiological to in vitro and in vivo experimental
      settings have provided convincing evidence that different aspects of brain lipid
      metabolism may influence Alzheimer disease pathogenesis through effects on beta
      amyloid deposition and clearance. It has been demonstrated that transcription
      factors called nuclear liver X receptors (LXR) and their responsive genes provide
      natural regulatory mechanisms and influence AD pathogenesis through their
      modulatory effects on intracellular cholesterol content, cholesterol efflux and
      possibly via anti-inflammatory mechanisms. Here, we provide a brief summary of
      the approaches undertaken by different groups that lead to the nowadays working
      model of LXR and ABCA1 regulatory role in brain amyloidogenesis and amyloid
      clearance and we highlight the therapeutic potential of LXR agonists.

PMID- 17430244
TI  - Liver X receptor-mediated gene regulation and cholesterol homeostasis in brain:
      relevance to Alzheimer's disease therapeutics.
AB  - Liver X receptors (LXRalpha and LXRbeta) are oxysterol receptors that function as
      master transcription factors mediating cholesterol homeostasis in the periphery.
      LXRs regulate the levels of the ABCA1 and ABCG1 cholesterol transporters as well
      as apolipoproteins (apoE and apoC) in various cells thereby affecting cholesterol
      transport and metabolism. In the brain, LXRs regulate ABCA1 in both neurons and
      glia resulting in cholesterol efflux from these cells. In addition, the
      expression of apolipoprotein E (apoE), synthesized primarily by astrocytes and
      microglia, is also upregulated by LXR agonists. As both apoE and the ABCA1
      transporter are intimately involved in amyloid-beta peptide (Abeta) transport and
      clearance, activation of these genes by LXR agonists in brain may have a
      significant impact on Abeta deposition and amyloid/neuritic plaque formation.
      Furthermore, LXR activation has been shown to have significant anti-inflammatory
      properties. Taken together, these findings suggest that brain-penetrable LXR
      agonists or modulators may be useful therapeutic agents for the treatment and
      (or) prevention of Alzheimer's disease.

PMID- 17430245
TI  - Systemic inflammation, infection, ApoE alleles, and Alzheimer disease: a position
      paper.
AB  - Alzheimer disease (AD) includes inflammatory processes in the senile plaques and
      surrounding glia, with increased expression of acute phase proteins such as C
      reactive protein (CRP) and IL-6. Increased IL-6 expression during normal brain
      aging suggests a link of age-related inflammation to the onset of AD during
      aging. Blood levels of CRP and IL-6 are also associated with higher risk of
      Alzheimer disease and cognitive decline during aging. Some infections are known
      to induce inflammation and amyloid deposits. For example, HIV induces the
      deposition of the same beta-amyloid as in Alzheimer disease. The ApoE4 allele may
      increase HIV-associated dementia, in addition to its well-known effect on
      accelerating the onset age of AD. Many other adverse effects of apoE4 are
      recognized, which suggested the hypothesis that apoE4 persists in human
      populations because of balancing selection (Charlesworth-Martin hypothesis). The
      apoE4 allele was acquired during human evolution and may have conferred initial
      advantages in pathogen resistance. As evidence for this hypothesis, apoE4
      carriers have less severe liver damage during hepatitis C infections. As human
      lifespan lengthened and cognitive and cardiovascular health became more
      important, the apoE3 allele spread, while the E4 allele was maintained in all
      populations by balancing selection.

PMID- 17430246
TI  - Role of the blood-brain barrier in the pathogenesis of Alzheimer's disease.
AB  - Cerebrovascular dysfunction contributes to the cognitive decline and dementia in
      Alzheimer's disease (AD), and may precede cerebral amyloid angiopathy and brain
      accumulation of the Alzheimer's neurotoxin, amyloid beta-peptide (Abeta). The
      blood-brain barrier (BBB) is critical for brain Abeta homeostasis and regulates
      Abeta transport via two main receptors, the low density lipoprotein receptor
      related protein 1 (LRP1) and the receptor for advanced glycation end products
      (RAGE). According to the neurovascular hypothesis of AD, faulty BBB clearance of
      Abeta through deregulated LRP1/RAGE-mediated transport, aberrant angiogenesis and
      arterial dysfunction may initiate neurovascular uncoupling, Abeta accumulation,
      cerebrovascular regression, brain hypoperfusion and neurovascular inflammation.
      Ultimately these events lead to BBB compromise and chemical imbalance in the
      neuronal 'milieu', and result in synaptic and neuronal dysfunction. Based on the
      neurovascular hypothesis, we suggest an array of new potential therapeutic
      approaches that could be developed for AD to reduce neuroinflammation, enhance
      Abeta clearance and neurovascular repair, and improve cerebral blood flow. RAGE
      based and LRP1-based therapeutic strategies have potential to control brain Abeta
      in AD, and possibly related familial cerebrovascular beta-amyloidoses. In
      addition, we have identified two vascularly restricted genes, GAX (growth arrest
      specific homeobox), which controls LRP1 expression in brain capillaries and brain
      angiogenesis, and MYOCD (myocardin), which controls contractility of cerebral
      arterial smooth muscle cells and influences cerebral blood flow. These findings
      provide insights into new pathogenic pathways for the vascular dysfunction in AD
      and point to new therapeutic targets for AD.

PMID- 17430247
TI  - Glucocorticoids, the etiology of obesity and the metabolic syndrome.
AB  - In mammals, glucocorticoid actions appear to have evolved to maintain and enhance
      energy stores to be used for life-saving gluconeogenesis. They act on the brain
      to stimulate search behaviors, palatable feeding and emotionally relevant
      memories, and they act on the body to mobilize stored peripheral energy and
      direct it to central depots that serve the substrate needs of the liver. Our work
      in rats shows that searching and intake of palatable foods (sucrose, saccharin
      and lard) are stimulated by corticosterone in a dose-related fashion.
      Adrenalectomized rats gain weight poorly, have low fat content, increased
      sympathetic neural and hypothalamo-pituitary-adrenal outflow, and altered
      behaviors. Replacement with corticosterone reverses these effects. Surprisingly,
      when such rats are provided with 30% sucrose to drink, in addition to saline, all
      of the usual effects of adrenalectomy are corrected without corticosterone. We
      hypothesize that there is a metabolic feedback system that decreases stress
      responsiveness. Although we have not yet identified the signal associated with
      sucrose drinking, the weight of mesenteric fat correlates inversely with
      hypothalamic corticotropin-releasing factor (CRF). When rats eat lard and sucrose
      ad libitum, fat stores increase and CRF, ACTH and corticosterone responses are
      reduced. During stress, chow intake decreases but intake of lard and sucrose does
      not. Our current working model suggests that palatability signals and neural
      signals from fat stores act on brain to reduce activity in the central stress
      response system. Correlative results from a clinical study support the powerful
      role of small changes in glucocorticoids in type 2 diabetes.

PMID- 17430249
TI  - Gestational programming of offspring obesity: a potential contributor to
      Alzheimer's disease.
AB  - Obesity and its related diseases are the leading cause of death in western
      society, with associated risks of hypertension, coronary heart disease, stroke,
      diabetes, and breast, prostate and colon cancer. Recent epidemiologic data
      indicate an increased risk of Alzheimer's disease in association with adult
      obesity. There is now convincing evidence that, in both human and animal models,
      the in utero environment may impact on fetal developmental processes, altering
      offspring homeostatic regulatory mechanisms. "Gestational programming" may result
      in altered cell number, organ structure, hormonal set points or gene expression,
      with effects being permanent or expressed only at select offspring ages (e.g.,
      newborn, adult). Our laboratory and others have demonstrated that low birth
      weight rats, induced by maternal food restriction or uterine artery ligation,
      paradoxically develop adult obesity with glucose intolerance and hypertension.
      Recent studies indicate alterations in peripheral (hepatic) and central
      (hippocampus) IGF-1 gene expression and epigenetic regulation among these
      offspring. These findings suggest that potential risk factors for the development
      of Alzheimer's disease may be present as early as newborn life.

PMID- 17430248
TI  - A new glucocorticoid hypothesis of brain aging: implications for Alzheimer's
      disease.
AB  - The original glucocorticoid (GC) hypothesis of brain aging and Alzheimer's
      disease proposed that chronic exposure to GCs promotes hippocampal aging and AD.
      This proposition arose from a study correlating increasing plasma corticosterone
      with hippocampal astrocyte reactivity in aging rats. Numerous subsequent studies
      have found evidence consistent with this hypothesis, in animal models and in
      humans. However, several results emerged that were inconsistent with the
      hypothesis, highlighting the need for a more definitive test with a broader panel
      of biomarkers. We used microarray analyses to identify a panel of hippocampal
      gene expression changes that were aging-dependent, and also corticosterone
      dependent. These data enabled us to test a key prediction of the GC hypothesis,
      namely, that the expression of most target biomarkers of brain aging should be
      regulated in the same direction (increased or decreased) by both GCs and aging.
      This prediction was decisively contradicted, as a majority of biomarker genes
      were regulated in opposite directions by aging and GCs, particularly inflammatory
      and astrocyte-specific genes. Thus, the initial hypothesis of simple positive
      cooperativity between GCs and aging must be rejected. Instead, our microarray
      data suggest that in the brain GCs and aging interact in more complex ways that
      depend on the cell type. Therefore, we propose a new version of the GC-brain
      aging hypothesis; its main premise is that aging selectively increases GC
      efficacy in some cell types (e.g., neurons), enhancing catabolic processes,
      whereas aging selectively decreases GC efficacy in other cell types (e.g.,
      astrocytes), weakening GC anti-inflammatory activity. We also propose that
      changes in GC efficacy might be mediated in part by cell type specific shifts in
      the antagonistic balance between GC and insulin actions, which may be of
      relevance for Alzheimer's disease pathogenesis.

PMID- 17430250
TI  - How and when environmental agents and dietary factors affect the course of
      Alzheimer's disease: the "LEARn" model (latent early-life associated regulation)
      may explain the triggering of AD.
AB  - Alzheimer's disease (AD) is currently the most prominent form of dementia among
      the elderly. Although AD manifests in late adult life, it is not clear when the
      disease actually starts and how long the neuropathological processes take to
      develop AD. The major unresolved question is the timing and the nature of
      triggering leading to AD. Is it an early or developmental and/or late phenomenon
      and what are the factors that trigger the cascade of pathobiochemical processes?
      To explain the etiology of AD one should consider the neuropathological features,
      such as neuronal cell death, tau tangles, and amyloid plaque, and environmental
      factors associated with AD, such as diet, toxicological exposure, and hormonal
      factors. Current dominant theories of AD etiology are "protein-only", they
      attribute the cause of the disease directly to the activities of associated
      proteins once they have been produced; the major limitation is that protein
      aggregations occur "late in the game". Development and progression of AD has not
      been explained by protein-only models. In view of this limitation, we propose a
      "Latent Early-Life Associated Regulation" (LEARn) model, which postulates a
      latent expression of specific genes triggered at the developmental stage.
      According to this model, environmental agents (e.g., heavy metals), intrinsic
      factors (e.g., cytokines), and dietary factors (e.g., cholesterol) perturb gene
      regulation in a long-term fashion, beginning at early developmental stages;
      however, these perturbations do not have pathological results until significantly
      later in life. For example, such actions would perturb APP gene regulation at
      very early stage via its transcriptional machinery, leading to delayed
      overexpression of APP and subsequently of Abeta deposition. This model operates
      on the regulatory region (promoter) of the gene and by the effect of methylation
      at certain sites within the promoter of specific genes. Promoters tend to have
      both positive and negative regulatory elements, and promoter activity can be
      altered by changes in the primary DNA sequence and by epigenetic changes through
      mechanisms such as DNA methylation at CpG dinucleotides or oxidation of guanosine
      residues. The basis of the LEARn model is that environmental factors, including
      metals and dietary factors, operate by interfering the interaction of methylated
      CpG clusters with binding proteins, such as MeCP2 and SP1. The LEARn model may
      explain the etiology of AD and other neuropsychiatric and developmental
      disorders.

PMID- 17430251
TI  - Clinical and pathological data of 10 malignant pheochromocytomas: long-term
      follow up in a single institute.
AB  - BACKGROUND: Malignant pheochromocytomas are rare. Many controversies still exists
      in clinical practice. We report the clinical and histological data of long-term
      follow up in 10 patients with malignant pheochromocytoma. METHODS: The clinical
      charts of 10 patients with malignant pheochromocytoma from a single institute
      were reviewed. The diagnosis of pheochromocytoma was confirmed at surgery. All
      patients had metastases in sites where chromaffin tissue was normally absent.
      RESULTS: The median follow-up period was 5.5 years (range, 2-20 years). Extra
      adrenal tumors occurred in four patients including paraganglioma tumors in three
      cases and bladder tumor in one case. Regional lymph node metastases were noted in
      six patients. Distant metastases were located in the lungs of two patients, in
      the bones of two patients and in the liver of one patient. Histological
      characteristics were not helpful for diagnosis of malignancy and for prediction
      of prognosis. Metastases were present in postoperative pathology in seven
      patients. In another three patients, metastases were discovered 6 months to 10
      years after surgery. Three patients received chemotherapy and one patient
      received combination therapy of high-dose (131)I-meta-iodobenzylguanidine ((131)I
      MIBG) therapy and chemotherapy. All patients achieved long-term survival except
      for two who died of metastasis 1.5 years and 2 years after diagnosis.
      CONCLUSIONS: Early complete resection and adjunctive lymphadenectomy can cure
      malignancy. Close long-term follow up for more than 10 years after surgery is
      necessary in patients with pheochromocytoma. The possibility of malignancy should
      be kept in mind even though the initial pathology is benign.

PMID- 17430252
TI  - Impact of salvage therapy for biochemical recurrence on health-related quality of
      life following radical prostatectomy.
AB  - OBJECTIVE: To determine the impact of salvage therapy for prostate-specific
      antigen (PSA) recurrence on the health-related quality of life (HRQOL) of
      patients after radical retropubic prostatectomy (RP). METHODS: Between January
      2000 and December 2003, a total of 249 patients who underwent RP were available
      for 2-year follow up. Of the respondents, 203 men did not show evidence of
      recurrence (group A), and 46 men received salvage hormonal therapy and/or
      radiotherapy after RP because of a rise in PSA (group B). The general and
      prostate-target HRQOL was assessed with the Medical Outcomes Study 36-Item Short
      Form and University of California, Los Angeles Prostate Cancer Index,
      respectively. Patients completed the HRQOL instruments by mail at baseline and at
      24 months after RP. RESULTS: All of the patients completed both questionnaires.
      At baseline no significant differences were found between the two groups in any
      of the HRQOL domains. There were significant improvements in mental health and
      social function for the patients without biochemical recurrence postoperatively.
      Repeated measure anova revealed significantly different patterns of alteration in
      several general HRQOL domains among the treatment groups. The urinary and bowel
      domains were equivalent between the two treatment groups at baseline and 24
      months after RP. The patients treated with salvage hormonal therapy tended to
      show delayed recovery of sexual function. CONCLUSION: Using a self-administered
      questionnaire, biochemical recurrence following RP was found to impose a
      substantial burden in patients with localized prostate cancer.

PMID- 17430253
TI  - Prostate-specific antigen half-life and pretreatment prostate-specific antigen:
      crucial predictors for prostate-specific antigen trend in delayed-combined
      androgen blockade therapy.
AB  - PURPOSE: To elucidate the crucial predictors for prostate-specific antigen (PSA)
      trends and determine the usage of anti-androgen treatment during delayed-combined
      androgen blockade (CAB) leading to a PSA level below 0.2 ng/mL. MATERIALS AND
      METHODS: From January 2001 to December 2004, 105 prostate cancer patients were
      enrolled. Medical castration and anti-androgen treatment were used sequentially
      and termed delayed-CAB. The first goal was to maintain an undetectable PSA level.
      The nadir PSA was determined after medical castration only. Anti-androgen was
      given if a PSA level of more than 0.2 ng/mL was observed and the subsequent PSA
      response was assessed. All cases were divided into two groups based on whether
      the PSA was lower (n = 59) or higher (n = 46) than 0.2 ng/mL. An analysis of the
      difference between the two groups was calculated. RESULTS: The median of the
      initial PSA level in the lower group was lower than in the higher group with a
      95% cut-off level of 40 ng/mL. The median PSA half-life in the lower group was
      also reduced with a 95% cut-off of 3.6 months. In a multivariate analysis, the
      pretreatment PSA level and the PSA half-life exhibited a significant correlation
      between the two groups. Anti-androgen treatment was given to 26 cases in the
      higher group. The PSA increased in one case, decreased to less than 0.2 ng/mL in
      17 cases and remained over 0.2 ng/mL in eight cases. CONCLUSION: Both the PSA
      half-life and the pretreatment PSA level were useful markers for predicting the
      PSA trends to determine the optimal use of anti-androgen treatment during delayed
      CAB.

PMID- 17430255
TI  - Complex urethral disruptions: in pursuit of a successful reconstruction.
AB  - OBJECTIVES: We analyzed the methods and outcomes of urethroplasty in men with
      complex urethral disruptions. METHODS: The medical records of 40 men with complex
      urethral disruptions were analyzed. Surgical methods were individualized
      according to stricture location, severity and length of the stricture, bladder
      neck characteristics and presence of complicating factors. Patients were divided
      into four groups based on the above characteristics. RESULTS: End-to-end
      urethroplasty performed in six patients with short bulbar strictures (<3 cm) was
      successful in all. Elaborated perineal repair was performed in 10 patients with
      intermediate (3-6 cm) strictures with or without complicating factors. Elaborated
      perineal repair with urethral substitution was performed in nine patients with
      long segment stricture (>6 cm). Abdominal transpubic repair was successfully
      applied to patients with rectourethral fistula or lacerated bladder neck. Success
      rate of anastomotic urethroplasty was 95% while over all success rate was 85%.
      CONCLUSION: Guidelines for urethral reconstruction of complex urethral
      disruptions are predicated on stricture length, location, bladder neck
      characteristics and associated complicating factors. End-to-end urethroplasty
      with stricture excision is highly reliable for short strictures for which
      previous operative repair have failed. Elaborated perineal repair is extremely
      versatile for intermediate and longer strictures with associated complicating
      factors. Abdominal transpubic urethroplasty is effective for patients with
      rectourethral fistula or lacerated bladder neck.

PMID- 17430256
TI  - Effect of intraurethral captopril gel on the recurrence of urethral stricture
      after direct vision internal urethrotomy: Phase II clinical trial.
AB  - OBJECTIVE: The purpose of this study is to evaluate the effect of intraurethral
      captopril gel as an antifibrotic agent on patients with urethral stricture.
      MATERIALS AND METHODS: In the first phase of clinical trial, 13 rabbits were
      included and local side-effects of captopril gel were evaluated. In the second
      phase, 56 patients were enrolled from April 2004 to January 2006. After internal
      urethrotomy the patients were classified into three patient groups: (i) received
      placebo gel (group I); (ii) received 0.1% captopril gel (group II); and (iii)
      instilled 0.5% captopril gel intraurethrally (group III). RESULTS: In phase I, no
      significant local side-effects were seen in the urethra of rabbits. In phase II,
      the mean age of the patients was 39.5 and the mean follow-up duration was 16
      months. The most common etiology of the urethral stricture in the patients was
      iatrogenic (35.7%), most of their strictures had a depth of 0.5 cm or less
      (67.8%), and the length of most strictures was between 1 and 2 cm (41.1%). The
      patients' maximum urine flow increased more in groups II and III, than in group I
      (P < 0.04, P < 0.05, respectively). The recurrence rate was less in groups II and
      III than in group I (P < 0.05). In terms of the maximal urine flow and recurrence
      rate, no significant difference was seen between group II and group III (P =
      0.13, P = 0.21, respectively). CONCLUSION: Captopril gel is a safe, effective and
      non-toxic agent for decreasing the recurrence rate of the urethral stricture
      after internal urethrotomy. However, more studies, including more cases and a
      longer follow up, are needed to prove the effect of captopril gel on patients'
      urethra.

PMID- 17430257
TI  - Technique of anterior urethra urethroplasty using tunica albuginea of corpora
      cavernosa.
AB  - OBJECTIVE: Over previous years, urethral stricture has constantly created a great
      problem in efforts to find a permanent cure for it. We describe a technique of
      anterior urethroplasty using tunica albuginea of corpora cavernosa. METHODS:
      After a midline penoscrotal incision, the bulbar or penile urethra along with
      corpus spongiosum was dissected from the corpora cavernosa. Urethra was then
      rotated dorsally and the stricture was opened along its whole length. The walls
      of the slit urethra, along with the tunica albuginea of the corpus spongiosum,
      were sutured to the tunica albuginea of the corpora cavernosa at the 5 and 7
      o'clock position after passing an all silicon catheter. We performed this
      technique on 79 male patients, having anterior urethral stricture, ranging 18-60
      years of age (mean, 46 years). The etiology of stricture was trauma in 54,
      instrumentation in 12, infection in 10 and unknown in three. Follow ups were done
      at 4, 12 and 24 months by assessing patients' satisfaction rate along with a pre-
      and postoperative urethrogram, labeled as "good", "fair" and "poor". RESULTS:
      Good and fair results were considered as successful. The overall success rate was
      94.9%. The success rate remained same at 4 months (64 + 11) and decreased to
      93.7% (63 + 11) at 12 months and 89.9% (61 + 10) at 24 months. CONCLUSION: These
      observations show that anterior urethroplasty using tunica albuginea of corpora
      cavernosa have produced satisfactory results and are comparable with any other
      technique of urethroplasty. Thus, we strongly recommend the use of tunica
      albuginea of corpora cavernosa for anterior urethroplasty, which is
      histologically similar and anatomically located near the stricture.

PMID- 17430258
TI  - Impact of various modifiers on calcium oxalate crystallization.
AB  - OBJECTIVE: This work focuses on the behavior of in vitro calcium oxalate
      crystallization. The effects of several compounds on the kinetics of calcium
      oxalate crystallization were examined. METHODS: Rates of nucleation and
      aggregation of calcium oxalate crystals were derived from 30-min time-course
      measurements of optic density at 620 nm after mixing solutions containing calcium
      chloride and sodium oxalate at 37 degrees C, pH 5.7. The maximum increase of
      optic density with time, termed S(N), mainly reflects maximum rate of formation
      of new particles and thus crystal nucleation. After equilibrium has been reached,
      optic density decreases. No new particles were formed due to crystal aggregation.
      S(A) (the maximum slope of decrease of optic density at 620 nm with time,
      representing crystal aggregation) is derived from the maximum decrease in optic
      density. RESULTS: Among the modifiers studied, citrate decreased both S(N) and
      S(A) (P < 0.001). Magnesium was also found to inhibit the rate of nucleation and
      crystal aggregation, but it appeared in a non-concentrated manner. Nucleation and
      aggregation inhibition ratios were related inversely to concentration of albumin
      (P < 0.001). CONCLUSION: The growth and agglomeration of calcium oxalate crystals
      are differently modulated by various compounds. The treatments aiming at
      inhibiting crystallization of calcium oxalate can be better defined by these
      findings. And new treatment modalities can be developed.

PMID- 17430259
TI  - Effects of olprinone, a phosphodiesterase III inhibitor, on ischemic acute renal
      failure.
AB  - OBJECTIVE: Renal ischemic reperfusion injury (IRI) is unavoidable and is still
      one of the major problems in renal transplantation. The aim of this study was to
      investigate the effects of olprinone, a phosphodiesterase III inhibitor, on renal
      IRI. METHODS: After a right nephrectomy, renal IRI was induced in rats. Olprinone
      was given in two different ways: sustained systemic administration and transient
      local administration to the kidney. Control rats were treated with saline. Using
      a magnifying endoscope, the renal blood flow speed was measured at 23 h after
      reperfusion. Then, blood samples were collected, and kidney specimens were taken
      for histological study. In order to study the mechanism, we performed in vitro
      experiments, using human proximal renal tubular cells (HK-2) incubated with tumor
      necrosis factor (TNF)-alpha along with olprinone or saline, and interleukin (IL)
      8 was measured in the culture supernatant. RESULTS: In the saline group, the
      blood flow speed (BFS) was greatly reduced compared to that in normal kidneys. In
      both olprinone-treated groups, BFS of the renal microcirculation significantly
      increased, tubular damage and macrophage infiltration attenuated, and renal
      function greatly improved. Olprinone inhibited the increase in the IL-8 levels
      resulting from the incubation of HK-2 with TNF-alpha. CONCLUSIONS: Our study
      successfully demonstrates that olprinone has renoprotective properties when
      applied locally as well as systemically. The results suggest that olprinone might
      be clinically useful in renal transplantation for the donor kidney, the
      recipient, and even in treating acute renal failure.

PMID- 17430260
TI  - Effects of opioid subtypes on detrusor overactivity in rats with cerebral
      infarction.
AB  - AIM: In order to determine the influence of different opioid receptor subtypes on
      detrusor overactivity after left middle cerebral artery (MCA) occlusion,
      cystometric recordings were obtained in conscious rats. METHODS: Female Sprague
      Dawley rats were used in this study. Control cystometrography was followed by
      left MCA occlusion. The sham-operated (SO) rats underwent the same procedures
      except for MCA occlusion. [D-Ala(2), Phe(4), Gly(5)]-enkephalin (DAGO; mu-opioid
      agonist), [D-Pen(2,5)]-enkephalin (DPDPE; delta1-opioid agonist), deltorpin II
      (delta2-opioid agonist), and U-50488 (kappa-opioid agonist) were administered
      intracerebroventricularly at graded doses. The bladder capacity, residual volume,
      micturition threshold pressure, and bladder contraction pressure were determined.
      Finally, the volume of the infarction was measured. RESULTS: The
      intracerebroventricular administration of DAGO and DPDPE significantly increased
      the bladder capacity in the cerebrally infarcted (CI) and SO rats, but
      differences in the changes in bladder capacity between the CI and SO rats were
      not significant. Deltorpin II did not produce any changes in the bladder capacity
      in the CI or SO rats at any dose examined. However, the intracerebroventricular
      administration of U-50488 significantly increased the bladder capacity in the CI
      rats but not in the SO rats. None of the drugs affected the residual volume,
      micturition threshold pressure or bladder contraction pressure at any dosage
      examined. The mean infarcted volumes were not significantly different from those
      in the vehicle-treated rats. CONCLUSION: These results suggest that the opioid
      receptor subtypes, mu and delta1 in the brain, are related to the micturition
      reflex. Furthermore, the kappa opioid agonist might be useful for the suppression
      of detrusor overactivity caused by cerebral infarction.

PMID- 17430262
TI  - Establishment and characterization of androgen-independent human prostate cancer
      cell lines, LN-REC4 and LNCaP-SF, from LNCaP.
AB  - AIM: To investigate the mechanisms of androgen-independent growth in prostate
      cancer (PCa), we established two PCa cell lines, LN-REC4 and LNCaP-SF, from the
      androgen-dependent PCa cell line, LNCaP. MATERIALS AND METHODS: LN-Pre and LN
      REC4 cells were generated from LNCaP tumors grown on intact and castrated severe
      combined immunodeficient (SCID) mouse, respectively. After we cultured LNCaP
      cells under a steroid-free conditions for 6 months in vitro, LNCaP-SF cells were
      established. To show the character of LN-REC4 and LNCaP-SF cells, androgen
      sensitivity was investigated through examination of growth rate, and prostate
      specific antigen (PSA), androgen receptor (AR), p21, p27, and cyclin D1
      expression were examined by reverse transcription-polymerase chain reaction (RT
      PCR). Angiogenesis assay in vitro was carried out using conditioned medium. To
      examine the expression level of vascular endothelial growth factor (VEGF), RT-PCR
      and enzyme-linked immunosorbent assay were also done. RESULTS AND CONCLUSIONS: LN
      REC4 cells proliferated better than LNCaP cells in castrated mice and did well
      irrespective of castration, although responsiveness for androgen of LN-REC4 cells
      attenuated less than that of LNCaP cells in vitro. LNCaP-SF cells in castrated
      mice proliferated more rapidly than in normal mice. The PSA expression in LNCaP
      SF cells was still induced by androgen. Expression of AR, p21, p27 and cyclin D1
      were not changed in LN-REC4 and LNCaP-SF cells. Angiogenesis assay showed that
      both cells stimulated angiogenesis. LN-REC4 induced VEGF more than LNCaP and LN
      Pre cells. However, expression of VEGF per cell in LNCaP-SF was lower than LNCaP
      cells, suggesting that other factors might be involved in angiogenesis. These
      cell lines might be a useful tool for researching androgen-independent growth and
      treatments of recurred PCa.

PMID- 17430263
TI  - Cardiac metastasis of renal pelvic cancer.
AB  - A 66-year-old man was referred to our hospital with chest discomfort and
      shortness of breath. Seven months previously he had undergone a laparoscopic left
      nephroureterectomy for a left renal pelvic tumor and was given two cycles of
      adjuvant chemotherapy (methotrexate, epirubicin and cisplatin). Echocardiogram
      showed an 8-mm sized mass extending from the right atrium into the right
      ventricle. On computed tomography, multiple lung tumors, as well as the right
      atrial and ventricular mass, were seen. The patient died of acute heart failure
      caused by right ventricular outflow obstruction. On autopsy, a right atrial and
      ventricular metastasis of the initial transitional cell carcinoma was found. The
      patient's cause of death was acute heart failure as a result of cardiac
      metastasis of his initial renal pelvic carcinoma.

PMID- 17430264
TI  - Case of renal myxoma.
AB  - Renal myxomas are rare neoplasms. Only three cases have been convincingly
      diagnosed as renal myxoma. Here we report an additional case. The case was a 36
      year-old man and he was discovered incidentally at the regular health-check for
      chronic hepatitis B. Computed tomography showed 8 cm low-density tumor in the
      lower pole of the left kidney. The tumor was slightly enhanced by contrast
      agents. Magnetic resonance imaging revealed the tumor as low intensity on T(1)
      weighted imaging and high intensity on T(2)-weighted images. The tumor was
      enhanced by gadrinium enhancement homogeneously. The resected kidney contained
      semitranslucent, gelatinous, tan mass within the lower pole of the kidney. The
      microscopic examination showed the typical appearance of a myxoma, which
      consisted of large amounts of myxoid material containing a few uniformly
      scattered spindle cells The tumor cells showed immunoreactivity for vimentin but
      not for S-100 protein, epithelial membrane antigen, cytokeratin, alpha smooth
      muscle actin.

PMID- 17430265
TI  - Distinguishing splenosis from local recurrence of renal cell carcinoma using a
      technetium sulfur colloid scan.
AB  - Heterotropic splenic tissue in renal fossa is characteristically asymptomatic and
      is usually an incidental finding that has been reported to mimic renal or adrenal
      tumors. A 55-year-old man with renal cell carcinoma had undergone radical
      nephrectomy together with splenectomy because of disrupture of the splenic
      capsule. During a follow-up examination, three nodules were detected by computed
      tomography scan in the splenorenal area and they slowly enlarged. Although local
      recurrence was highly suspected, we decided to rule out splenosis. We
      successfully diagnosed these masses as ectopic splenic tissues by a technetium
      sulfur colloid scan and unnecessary surgical exploration was avoided.

PMID- 17430266
TI  - A case of primary leiomyoma of the ureter.
AB  - This report describes a case of primary leiomyoma of the ureter in which only
      partial ureterectomy was performed based on the diagnosis of benign tumor by
      rapid diagnosis using a frozen section during the operation. Surgical treatment
      was opted for upon diagnosis of a submucosal tumor of the right ureter, with no
      abnormal findings in the ureteral mucosa by ureteroscopy. To our knowledge, nine
      cases have been reported worldwide since 1955, suggesting this case to be the
      10th.

PMID- 17430267
TI  - Spurious prostate-specific antigen (PSA) recurrence after radical prostatectomy:
      interference by human antimouse heterophile antibodies.
AB  - Human antimouse heterophile antibodies (HAMA) are naturally occurring antibodies
      that can interfere with modern serum assays. We report a case of HAMA
      interference with a commonly used prostate-specific antigen (PSA) assay, leading
      to false elevation (2.17-2.46 ng/mL) after radical prostatectomy. Pre-operative
      PSA was 4.4 ng/mL, and final pathology was Gleason 3 + 3, pT2cNXMX. This markedly
      elevated postoperative PSA led to unnecessary imaging for metastasis and
      psychological distress to the patient. Direct measurement of HAMA in the
      patient's serum yielded a value of 440 ng/mL (<74 ng/mL). An alternate PSA assay
      using goat detection antibody eliminated interference, with all values 0.05
      ng/mL. When a patient's PSA is inconsistent with the clinical scenario, one
      should consider immunological interference by HAMA in PSA assays.

PMID- 17430268
TI  - Successful superselective arterial embolization for post-traumatic high-flow
      priapism.
AB  - We report a case of high-flow priapism treated successfully with superselective
      embolization of the cavernous artery. An 18-year-old man presented to our
      hospital 12 days after having been struck in the perineum by the corner of a
      skateboard. Immediately after the injury, he suffered painless sustained
      incomplete erection. High-flow priapism was diagnosed on the basis of cavernosal
      blood gas analysis and color Doppler ultrasonography findings. Right internal
      pudendal arteriography showed blood pooling in the cavernosum as a result of a
      broken artery. We identified the precise position of the arterial-venous fistula
      and embolized it superselectively with gelatin sponge particles. The fistula
      disappeared completely. One year later, the patient's erectile function was
      completely restored, and there had been no recurrence of the priapism. According
      to the American Urological Association guidelines, conservative treatment should
      be attempted first for high-flow priapism. In our review of the literature,
      superselective arterial embolization could be an alternative treatment after more
      than 3 weeks of conservative treatment.

PMID- 17430269
TI  - Leiomyoma of the corpus cavernosum of the penis.
AB  - While soft tissue tumors can occur in the penis, corpus cavernous tumors are
      rare. Reported cases of corpus cavernous tumors are from metastases of advanced
      malignancy, such as cancers of the bladder, prostate, rectosigmoid colon, kidney,
      pancreas, liver, testis and nasopharynx. Primary corpus cavernous tumors are
      extremely rare and have possibly never been reported before. Herein, we report a
      case of leiomyoma of the corpus cavernosum. After the diagnosis of leiomyoma was
      established, total excision of the tumor was not attempted and the tumor remained
      unchanged in size and shape over a follow-up period of 15 months.

PMID- 17430270
TI  - Ipsilateral right testicular metastasis from renal cell carcinoma in a responder
      patient to interleukine-2 treatment.
AB  - We present a case of metastatic spreading to the testicle in a 46-year-old
      patient with renal cell carcinoma, "clear-cell" type, during interleukin-2
      combined subcutaneous plus aerosol treatment. Testicular metastasis occurred
      while the patient showed a response to the treatment with disappearance of lung
      lesions and reduction of lymph-nodes lesions. After orchiectomy with spermatic
      cord resection and disease re-evaluation confirming the previous response, the
      patient re-started immunotherapy. The contrast between systemic disease response
      to treatment and disease testicular progression might be explained by a relative
      insensitivity of the testicle to interleukin-2 immunotherapy as a result of a
      possible establishment of an immunosuppressive microenvironment. We believe that
      the rarity of this metastatic site and the intriguing possible mechanisms at its
      base, makes an interesting case for clinicians.

PMID- 17430271
TI  - Upper gastrointestinal hemorrhage as a rare extragonadal presentation of seminoma
      of testis.
AB  - A rare case of a gastric presentation of a seminoma with burned out primary
      testicular tumor is described. The patient initially presented with upper
      gastrointestinal hemorrhage. Endoscopic biopsies were suggestive of seminoma, and
      testicular ultrasound revealed a focal lesion and testicular microcalcification.
      Treatment consisted of bilateral orchidectomy, followed by four cycles of
      etoposide and bleomycin, where a complete response was achieved. Testicular
      histology was consistent with the "burned out" phenomenon and no tumor cells were
      found. There are only two previously reported cases of extragonadal seminoma in
      the stomach.

PMID- 17430272
TI  - Effects of flutamide as a second-line agent for maximum androgen blockade of
      hormone refractory prostate cancer.
AB  - We analyzed clinical effects of flutamide as a second-line agent for maximum
      androgen blockade (MAB) in patients with relapsing prostate cancer who received
      bicalutamide as the first-line MAB agent. This study included 13 patients with
      progressive prostate cancer who had relapsed after first-line MAB, with
      bicalutamide at 80 mg/day. After checking for antiandrogen withdrawal syndrome,
      they were given flutamide at 375 mg/day as second-line MAB. The effectiveness of
      that therapy was evaluated by changes in prostatic specific antigen (PSA) levels,
      with response defined as a decrease of greater than 50% from the start of
      therapy. We also compared several factors between responders and non-responders.
      Nine (69.2%) of the 13 patients showed a decrease in PSA levels, of whom five
      (38.5%) had a greater than 50% decrease and were defined as responders. The
      median duration of PSA response was 11.0 months (range 5-20 months). Patients who
      had a longer duration of response to first-line MAB had a significantly greater
      response to second-line MAB. For advanced prostate cancer patients who progressed
      on first-line MAB with bicalutamide, flutamide administration as a second-line
      antiandrogen was found to be relatively effective, especially for those who
      showed a longer duration of response to the first-line MAB. Our results confirm
      previous findings that MAB using flutamide is an effective second-line hormonal
      therapy.

PMID- 17430273
TI  - Effect of experimentally induced Escherichia coli epididymo-orchitis and
      ciprofloxacin treatment on rat spermatogenesis.
AB  - We investigated the effects of epididymo-orchitis and ciprofloxacin on rat
      testicular histology and spermatogenesis. The control group underwent left
      orchiectomy. The second group received oral ciprofloxacin (150 mg/kg/day) for 10
      days. Escherichia coli (10(6) cfu/mL, 0.1 mL) was injected into the proximal
      right ductus deferens in the third group. The fourth group received ciprofloxacin
      treatment 48 h after E. coli inoculation. In groups 3 and 4, bilateral
      orchiectomy was performed 14 days after the challenge. In healthy rats,
      ciprofloxacin caused recognizable histological damage associated with a mild
      decrease in testicular volume and sperm concentration. Infected testicles in
      groups 3 and 4 revealed severe histological damage associated with severe
      testicular atrophy and impaired spermatogenesis that were more significant in
      infected rats which received ciprofloxacin treatment. Contralateral testicles in
      these animals showed similar histopathological changes to a lesser extent. The
      results of our study suggest a gonadotoxic potential for ciprofloxacin and this
      potential in humans should be addressed with further studies.

PMID- 17430276
TI  - Reflections on professionalism, medical politics and moving countries.

PMID- 17430277
TI  - Assessing professionalism in the context of an objective structured clinical
      examination: an in-depth study of the rating process.
AB  - INTRODUCTION: Professionalism is fundamental to the practice of medicine.
      Objective structured clinical examinations (OSCEs) have been proposed as
      appropriate for assessing some aspects of professionalism. This study
      investigated how raters assign professionalism ratings to medical students'
      performances in OSCE encounters. METHODS: Three standardised patients, 3 doctor
      preceptors, and 3 lay people viewed and rated 20 videotaped encounters between
      3rd-year medical students and standardised patients. Raters recorded their
      thoughts while rating. Qualitative and quantitative analyses were conducted.
      Comments about observable behaviours were coded, and relative frequencies were
      computed. Correlations between counts of categorised comments and overall
      professionalism ratings were also computed. RESULTS: Raters varied in which
      behaviours they attended to, and how behaviours were evaluated. This was true
      within and between rater type. Raters also differed in the behaviours they
      consider when providing global evaluations of professionalism. CONCLUSIONS: This
      study highlights the complexity of the processes involved in assigning ratings to
      doctor-patient encounters. Greater emphasis on behavioural definitions of
      specific behaviours may not be a sufficient solution, as raters appear to vary in
      both attention to and evaluation of behaviours. Reliance on global ratings is
      also problematic, especially if relatively few raters are used, for similar
      reasons. We propose a model highlighting the multiple points where raters viewing
      the same encounter may diverge, resulting in different ratings of the same
      performance. Progress in assessment of professionalism will require further
      dialogue about what constitutes professional behaviour in the medical encounter,
      with input from multiple constituencies and multiple representatives within each
      constituency.

PMID- 17430278
TI  - Altruism revisited: a comparison of medical, law and business students'
      altruistic attitudes.
AB  - OBJECTIVE: Although the concept of altruism in medicine has a long tradition in
      Western thought, little empirical research has been carried out recently in this
      area. This study compares the altruistic attitudes of medical, legal and business
      students. METHODS: We used a cross-sectional survey to compare the altruistic
      attitudes of 3 types of contemporary 'professional' students, those in medicine,
      law and business. RESULTS: The results suggest that medical students report more
      altruistic attitudes than legal students, but not than business students.
      Overall, female students reported stronger attitudes consistent with altruism
      compared with males; African-American and Hispanic students reported more
      altruistic attitudes compared with White students. CONCLUSIONS: Our results
      suggest that the recent trend in recruiting more women and under-represented
      minority group members into medicine may have a positive impact on altruism in
      the profession, if we can assume that attitudes correlate with behaviours.

PMID- 17430279
TI  - Documenting attitude changes towards homeless people: comparing two standardised
      surveys.
AB  - CONTEXT: Curricula about the care of homeless patients have been developed to
      improve stigmatising attitudes towards patients living in poverty. The Attitudes
      Toward Homelessness Inventory (ATHI) and the Attitudes Towards the Homeless
      Questionnaire (ATHQ) are both validated instruments developed to assess attitudes
      towards homeless patients. Although these surveys have similar goals, it is not
      clear which is superior for documenting attitude changes among doctors in
      training. METHODS: Seven cohorts of Year 2 and 3 primary care internal medicine
      residents at an urban public hospital in the USA completed the ATHI and ATHQ in a
      confidential manner before and after a 2-week rotation on health care for
      homeless patients (n = 25). RESULTS: Both the ATHI (P < 0.001) and the ATHQ (P =
      0.050) documented changes in residents' attitudes. The magnitude of the pre/post
      change was 0.63 per item for the ATHI and 0.13 per item for the ATHQ. When the
      ATHI per-item change was standardised to reflect the change that would be
      expected if there were 5 response choices instead of 6, the per-item change for
      the ATHI was 4.1-fold greater than for the ATHQ (P = 0.001). Residents improved
      their responses to 1 of every 8 statements on the ATHQ and 1 of every 2
      statements on the ATHI after the course. CONCLUSIONS: Both the ATHI and the ATHQ
      documented improvement in residents' attitudes after a 2-week homeless medicine
      curriculum. However, the ATHI was 4 times more responsive to change. These
      findings suggest that the ATHI is superior for detecting changes in attitudes
      after an educational intervention.

PMID- 17430280
TI  - Career preferences of graduate and non-graduate entrants to medical schools in
      the UK.
AB  - OBJECTIVE: Recent UK policy has been to increase substantially the number of
      graduate entrants to medical schools. Our aim was to study whether graduate and
      non-graduate entrants have different long-term career preferences. METHODS: We
      conducted postal questionnaire surveys of medical qualifiers from all UK medical
      schools in 1999, 2000 and 2002, surveyed 1 year after qualification, and
      qualifiers of 1999 and 2000, surveyed 3 years after qualification. RESULTS: By
      Year 3 after qualification, general practice was the choice of 33% of men
      graduate entrants and 21% of men non-graduates ( = 12.5, P < 0.001) and of 43% of
      women graduates and 38% of women non-graduates ( = 1.6, P = 0.2). Surgery was a
      much less popular choice for men graduate entrants than for men non-graduates;
      but similar percentages of women graduate and non-graduate entrants chose
      surgery. A lower percentage of graduate entrants than of non-graduates favoured
      paediatrics. Other differences between graduates and non-graduates were generally
      small. General practice was the preferred career for a much lower percentage of
      those who took an intercalated degree while at medical school, than of those who
      did not. CONCLUSIONS: Increasing graduate entry to medical school is likely to
      increase the percentage of doctors who want to become general practitioners, but
      only modestly so. It may also lead to a decline in the percentages choosing
      surgery and paediatrics. Otherwise, at least on the current criteria used for
      selecting students, increasing graduate entry will probably not make much
      difference to the percentage of newly qualified doctors seeking careers in
      different branches of practice.

PMID- 17430281
TI  - Medical school selection: impact of dysfunctional tendencies on academic
      performance.
AB  - PURPOSE: Dysfunctional personality characteristics have a negative impact on the
      learning process, academic motivation, academic grades and course attendance.
      They are associated with higher levels of anxiety and negative mood before
      examinations, a lack of self-confidence and fear of failure, social skills
      deficits, and personal and social relationship problems. Dysfunctional
      personality characteristics inhibit interpersonal working relationships and are
      detrimental to team effectiveness. Previous research revealed that the majority
      of students selected into an Australian undergraduate medical programme via the
      process of academic merit, application and interview reported elevated levels of
      dysfunctional personality characteristics. Our research now identifies those
      patterns of dysfunctional behaviour that impacted on academic grades over the
      first 3 years of the medical programme. METHODS: Dysfunctional personality
      characteristics in a sample of Australian undergraduate medical students were
      assessed with the Hogan Development Survey (HDS). The scores of 139 students were
      then correlated with their end-of-year examination marks for each of the first 3
      years of medical training, and their average grade. RESULTS: Pearson's bivariate
      correlation analysis revealed that there were a number of significant negative
      relationships between academic grades and the HDS syndromes of Away and Against.
      There were significant positive relationships between academic grades and the HDS
      syndrome of Diligent. CONCLUSIONS: To enrol and teach students who fail to
      graduate, need to repeat, choose not to pursue a career in medicine upon
      graduation, or become inefficient practitioners is costly. A measure of
      dysfunctional behaviour has the potential to predict academic performance and
      improve the cost-effectiveness of medical education.

PMID- 17430282
TI  - Effectiveness of selection in medical school admissions: evaluation of the
      outcomes among freshmen.
AB  - CONTEXT: In 2000 our medical school introduced a selection procedure (SP) for 10%
      of the otherwise randomly selected (RS) applicants. Students with excellent high
      school grade point averages (GPAs) were allowed direct access (DA) to our medical
      school. The selection procedure focused on medical comprehension, social and
      ethical understanding of health care, and communication and interpersonal skills.
      Objectives We aimed to establish how SP students compared with RS and DA students
      on motivation, academic achievement, study behaviour and extracurricular
      activities, and how these variables were interrelated within these groups.
      METHODS: In 2003, all Year 1 and 2 students were given a questionnaire on
      motivation, study behaviour and extra-curricular activities. Primary year GPAs
      were obtained from our administration department. Student groups were compared
      using descriptive statistics. The interrelationship between outcomes was tested
      using structural equation modelling. RESULTS: The questionnaire was returned by
      418 students (76%). Selection procedure students were significantly more highly
      motivated (59.4) than RS students (56.6) and DA students (52.1). This was not
      reflected in academic achievement (6.7), which was highest among DA students
      (7.2). Selection procedure students carried out more extra-curricular activities,
      often health care-related, and displayed more study behaviour. Academic
      achievement could not be explained by motivation and study behaviour but
      motivation affected study behaviour and health care-related extra-curricular
      activities. CONCLUSIONS: The more profound commitment of selected students to
      health care is not primarily reflected in academic achievement but in motivation,
      extra-curricular activities and study behaviour. Follow-up research including all
      pre-clinical and clinical years should demonstrate the stability of these
      characteristics and their effects on graduates' post-qualification clinical
      performance as practising doctors.

PMID- 17430284
TI  - Dropping out of medical school in the UK: explaining the changes over ten years.
AB  - CONTEXT: In the context of changing admissions criteria and an expanding medical
      school intake in the UK, we analysed the determinants of the medical school
      dropout probability. OBJECTIVES: We aimed to analyse the determinants of the
      probability that a student will drop out of medical school during Year 1 and to
      compare the results of this analysis over time. METHODS: We carried out logistic
      regression analysis for the 6 intake cohorts of 1990-92 and 1998-2000. RESULTS:
      Between 1990-92 and 1998-2000, there were substantial increases in both the size
      of the entry cohort and the proportion of students dropping out of medical
      school. A logit model for the 1990-92 and 1998-2000 cohorts reveals that the
      probability of dropping out depended on both the medical school attended and the
      personal characteristics of the student, including academic preparedness. Almost
      none of the increase in the dropout rate between the 2 cohort groups can be
      explained by changes in observable characteristics of the students over this
      period. Instead, most of the increase in the dropout rate is associated with
      changes at the level of the institution and in unobserved student
      characteristics. CONCLUSIONS: University effects, rather than changes in observed
      student characteristics, explain most of the increased dropout rate over the time
      period considered. Candidate explanations behind these effects include: less
      effective admissions policies; changing curricula; greater costs of attending
      medical school, and a growing mismatch between student and school
      characteristics. Testing between these competing hypotheses is left for future
      work.

PMID- 17430283
TI  - Multiple mini-interviews predict clerkship and licensing examination performance.
AB  - OBJECTIVE: The Multiple Mini-Interview (MMI) has previously been shown to have a
      positive correlation with early medical school performance. Data have matured to
      allow comparison with clerkship evaluations and national licensing examinations.
      METHODS: Of 117 applicants to the Michael G DeGroote School of Medicine at
      McMaster University who had scores on the MMI, traditional non-cognitive
      measures, and undergraduate grade point average (uGPA), 45 were admitted and
      followed through clerkship evaluations and Part I of the Medical Council of
      Canada Qualifying Examination (MCCQE). Clerkship evaluations consisted of
      clerkship summary ratings, a clerkship objective structured clinical examination
      (OSCE), and progress test score (a 180-item, multiple-choice test). The MCCQE
      includes subsections relevant to medical specialties and relevant to broader
      legal and ethical issues (Population Health and the Considerations of the Legal,
      Ethical and Organisational Aspects of Medicine[CLEO/PHELO]). RESULTS: In
      programme, MMI was the best predictor of OSCE performance, clerkship encounter
      cards, and clerkship performance ratings. On the MCCQE Part I, MMI significantly
      predicted CLEO/PHELO scores and clinical decision-making (CDM) scores. None of
      these assessments were predicted by other non-cognitive admissions measures or
      uGPA. Only uGPA predicted progress test scores and the MCQ-based specialty
      specific subsections of the MCCQE Part I. DISCUSSION: The MMI complements pre
      admission cognitive measures to predict performance outcomes during clerkship and
      on the Canadian national licensing examination.

PMID- 17430285
TI  - A cluster design controlled trial of arts-based observational skills training in
      primary care.
AB  - OBJECTIVE: To investigate whether the observational skills of doctors and nurses
      can be improved by arts-based observational skills training. METHODS: We carried
      out a cluster design, controlled trial involving 42 general practitioners and 26
      primary care nurses in 12 primary care practices in London. Six practices were
      allocated to the intervention arm and 6 to the control arm. The intervention
      group received 90 minutes of arts-based observational skills training. The
      control group received practical training in the management of psoriasis. Before
      and after this, control and intervention participants were asked to describe 3
      dermatological photographs. Descriptions were scored blindly against a
      predetermined marking key. Participants completed a questionnaire about the
      intervention, and about their own confidence in diagnosing and referring
      suspicious pigmented skin lesions. RESULTS: Post-intervention scores were
      significantly higher in the intervention group compared with the control group (P
      < 0.001). The majority of participants judged the intervention relevant,
      enjoyable and valuable. A majority lacked confidence in their dermatological
      knowledge and skills. DISCUSSION: This study provides statistically significant
      evidence that arts-based observational skills training can improve the
      observational skills of doctors and nurses. It is important not to overstate the
      clinical significance of these findings, and to recognise that observational
      skills are just one of many complex and subtle factors affecting the quality of
      the clinical process. Further research is needed to assess the existence, nature
      and clinical significance of longer-term benefits, and to identify differences
      between professional groups.

PMID- 17430286
TI  - Validation of MSAT: an instrument to measure medical students' self-assessed
      confidence in musculoskeletal examination skills.
AB  - CONTEXT: Self-assessment promotes reflective practice, helps students identify
      gaps in their learning and is used in curricular evaluations. Currently, there is
      a dearth of validated self-assessment tools in rheumatology. We present a new
      musculoskeletal self-assessment tool (MSAT) that allows students to assess their
      confidence in their skills in and knowledge of knee and shoulder examination.
      OBJECTIVES: We aimed to validate the 15-item MSAT, addressing its construct
      validity, internal consistency, responsiveness, repeatability and relationship
      with competence. METHODS: Participants were 241 Year 3 students in Newcastle upon
      Tyne and 113 Year 3 students at University College London, who were starting
      their musculoskeletal skills placement. Factor analysis explored the construct
      validity of the MSAT; Cronbach's alpha assessed its internal consistency;
      standardised response mean (SRM) evaluated its responsiveness, and test-retest,
      before and after a pathology lecture, assessed its repeatability. Its
      relationship with competence was explored by evaluating its correlation with
      shoulder and knee objective structured clinical examinations (OSCEs). Results The
      MSAT was valid in distinguishing the 5 domains it intended to measure: clinical
      examination of the knee; clinical examination of the shoulder; clinical anatomy
      of the knee and shoulder; history taking, and generic musculoskeletal anatomical
      and clinical terms. It was internally consistent (alpha = 0.93), responsive (SRM
      0.6 in Newcastle and 2.2 in London) and repeatable (intraclass correlation
      coefficient 0.97). Correlations between MSAT scores and OSCE scores were weak (r
      < 0.2). CONCLUSIONS: The MSAT has strong psychometric properties, thereby
      offering a valid approach to evaluating the self-assessment of confidence in
      examination skills by students. Confidence does not necessarily reflect
      competence; future research should clarify what underpins confidence.

PMID- 17430287
TI  - Peer-assisted learning: a novel approach to clinical skills learning for medical
      students.
AB  - OBJECTIVE: This study aimed to determine whether peer-assisted learning (PAL) can
      enhance clinical examination skills training. METHODS: Three student trainers
      studied small-group theory and clinical examination and provided PAL as extra
      tuition for 86 trainees. Trainees watched an examination video, were videotaped
      practising the examination and, after constructive feedback, repeated the
      examination. Responses to PAL were evaluated to attain an overview of trainee and
      trainer performance using visual analogue and Likert scale analyses. Year-group
      review was undertaken using questionnaires. RESULTS: Trainees evaluated all
      aspects of PAL highly, including their post-training confidence in examination
      skills (mean > 7.7 on a 10-cm scale), indicating that the PAL was effective.
      Written comments confirmed the students perceived the sessions as well structured
      and of high quality. Compared with trainees in the first groups, those from later
      groups gave all parameters similar or higher gradings. Those for interest (P =
      0.03) and appropriateness (P = 0.01) were significantly higher, suggesting that
      trainers may improve their technique with time. Students with previous degrees
      gave similar or lower gradings than standard entry students, with answers about
      post-training confidence and recommendation to friends being statistically lower
      (P < 0.006). Six months later, year-group analysis showed that 90% of trainees
      rated PAL highly, and 86% wished to become trainers. Of the trainers' year group,
      79% perceived that PAL training could improve examination skills. CONCLUSIONS: In
      the context of clinical skills training, PAL was highly evaluated across many
      parameters, including confidence after training. Student interest and enthusiasm
      supports suggestions that PAL could be a useful adjunct to clinical skills
      training.

PMID- 17430288
TI  - Improving diagnostic capabilities of medical students via application of
      cognitive sciences-derived learning principles.
AB  - PURPOSE: There is limited experimental evidence concerning how best to train
      students to perform differential diagnosis. We compared 2 different methods for
      training 2nd-year medical students to perform differential diagnosis (DDX) of
      heart failure: a traditional classroom-based lecture (control group) versus a
      cognitive sciences-based approach to DDX instruction implemented through a
      computer-based tutor (treatment group). METHODS: Following random assignment to
      either group, students were trained for 75 minutes, and then given a 40-item
      examination comprised of cases that varied along a typicality gradient from
      prototypical (easy) to less typical (hard). RESULTS: The treatment group
      diagnosed correctly significantly more test cases than the control group (74%
      versus 60%, respectively). The treatment group also diagnosed correctly
      significantly more cases at the extremes of the typicality gradient: 81% versus
      65%, respectively, for the prototypical cases; 65% versus 48%, respectively, for
      the most difficult cases. CONCLUSION: The ability to perform differential
      diagnosis is enhanced by training based upon principles of cognitive sciences.

PMID- 17430289
TI  - Research opportunities are stifled in hard-pressed National Health Service
      trusts.

PMID- 17430290
TI  - A call for student maternity leave in the medical educational system.

PMID- 17430291
TI  - Basic sciences education in the medical curriculum.

PMID- 17430292
TI  - How to create a geriatric medicine block in a university without a geriatrics
      department.

PMID- 17430293
TI  - Anticonvulsant efficacy of valproate-like carboxylic acids: a potential target
      for anti-bipolar therapy.
AB  - BACKGROUND: Bipolar disorder (BPD) is a severe and chronic illness, with a
      lifetime prevalence of approximately 1.5%. Despite the availability of some mood
      stabilizing drugs including lithium, valproate (valproic acid), lamotrigine and
      carbamazepine, BPD is characterized by high rates of recurrence, as treatment
      with these and other drugs is ineffective for and not well-tolerated by a
      significant percentage of patients. Most drugs currently used for the maintenance
      treatment of BPD are anticonvulsants (e.g., valproate, carbamazepine and
      lamotrigine). OBJECTIVES: The aim of this paper is to review the studies
      characterizing the anticonvulsant efficacy of valproate-like carboxylic acids and
      related compounds, some of which may have potential for the treatment of manic
      depressive illness. RESULTS: The data reviewed herein demonstrate clearly that
      some dietary fatty acids and other valproate-like carboxylic acids exhibit potent
      anticonvulsant activity, and may thus be candidates for mood stabilizing
      treatment options for BPD.

PMID- 17430294
TI  - Manic symptoms and impulsivity during bipolar depressive episodes.
AB  - OBJECTIVES: In contrast to the extensive literature on the frequent occurrence of
      depressive symptoms in manic patients, there is little information about manic
      symptoms in bipolar depressions. Impulsivity is a prominent component of the
      manic syndrome, so manic features during depressive syndromes may be associated
      with impulsivity and its consequences, including increased risk of substance
      abuse and suicidal behavior. Therefore, we investigated the prevalence of manic
      symptoms and their relationships to impulsivity and clinical characteristics in
      patients with bipolar depressive episodes. METHODS: In 56 bipolar I or II
      depressed subjects, we investigated the presence of manic symptoms, using Mania
      Rating Scale (MRS) scores from the Schedule for Affective Disorders and
      Schizophrenia (SADS), and examined its association with other psychiatric
      symptoms (depression, anxiety, and psychosis), age of onset, history of alcohol
      and/or other substance abuse and of suicidal behavior, and measures of
      impulsivity. RESULTS: MRS ranged from 0 to 29 (25th-75th percentile, range 4-13),
      and correlated significantly with anxiety and psychosis, but not with depression,
      suggesting the superimposition of a separate psychopathological mechanism.
      Impulsivity and history of substance abuse, head trauma, or suicide attempt
      increased with increasing MRS. Receiver-operating curve analysis showed that MRS
      could divide patients into two groups based on history of alcohol abuse and
      suicide attempt, with an inflection point corresponding to an MRS score of 6.
      DISCUSSION: Even modest manic symptoms during bipolar depressive episodes were
      associated with greater impulsivity, and with histories of alcohol abuse and
      suicide attempts. Manic symptoms during depressive episodes suggest the presence
      of a potentially dangerous combination of depression and impulsivity.

PMID- 17430295
TI  - The spectrum of substance abuse in bipolar disorder: reasons for use, sensation
      seeking and substance sensitivity.
AB  - OBJECTIVES: To examine the spectrum of alcohol and substance abuse, including
      reasons for use, in patients with bipolar I disorder, compared with patients with
      substance use disorder and healthy controls, with a specific focus on the
      relationship between substance use, substance sensitivity, other comorbid
      psychiatric symptoms and traits related to sensation seeking. METHODS: This study
      included 104 patients with bipolar I disorder (BPD I), of whom 57 (54.8%) met DSM
      IV criteria for lifetime alcohol or substance use disorder (BPD + SUD), 35
      patients with substance use disorder (SUD) and no psychiatric disorder and 50
      healthy controls. Assessments included the Structured Clinical Interview for DSM
      IV Axis I Disorders (SCID) and the Structured Clinical Interview for the Spectrum
      of Substance Use (SCI-SUBS). RESULTS: Patients with BPD + SUD and SUD had
      significantly higher scores on the SCI-SUBS domains of self-medication, substance
      sensitivity and sensation seeking compared with patients with BPD and healthy
      controls. Reasons for substance use did not differ between patients with BPD +
      SUD and patients with SUD. Those most frequently cited were: improving mood;
      relieving tension; alleviating boredom; achieving/maintaining euphoria; and
      increasing energy. CONCLUSIONS: Recourse to substances is associated with
      increased mood and anxiety symptoms, substance sensitivity, and sensation seeking
      among patients with BPD + SUD and SUD. Substance sensitivity and sensation
      seeking traits should be investigated in all patients with BPD as possible
      factors associated with a development of SUD, in order to warn patients of the
      specific risks related to improper use of medications and substances.

PMID- 17430296
TI  - Sensorimotor gating in manic and mixed episode bipolar disorder.
AB  - OBJECTIVES: Few studies have examined acoustic startle sensorimotor gating in
      bipolar disorder (BPD) despite the fact that patients with BPD have exhibited
      inhibitory dysfunctions on a variety of early information processing tasks. The
      present study aimed to expand the current literature through the investigation of
      electromyographic (EMG) measures of acoustic startle prepulse inhibition (PPI) in
      manic and mixed episode BPD. METHODS: Fourteen manic and 21 mixed episode BPD
      patients were compared to 32 healthy controls on acoustic startle measures of PPI
      using a 120-ms lead interval. RESULTS: Prepulse inhibition did not significantly
      differ across diagnostic groups (manic, mixed, control), and the presence of
      psychosis in the patient sample was not significantly related to PPI levels. With
      respect to startle response characteristics, patients in the mixed phase of the
      disorder showed prolonged prepulsed startle latency and attenuated responses to
      both probe-alone and prepulsed probes, though no differences in startle
      habituation were found across diagnostic groups. CONCLUSIONS: Although PPI
      deficits were not observed in either BPD sub-group, attenuated probe-alone and
      prepulsed startle magnitudes and reduced prepulse-induced latency facilitation in
      the mixed episode group is consistent with evidence that the mixed phase of BPD
      is associated with a more severe clinical outlook than other stages of the
      disorder. The absence of attenuated PPI in the patient sample may be due to the
      low incidence of psychosis in the BPD groups, though further studies are required
      to systematically assess the effects of symptom factors and clinical phase on
      sensorimotor gating in BPD.

PMID- 17430297
TI  - Context processing performance in bipolar disorder patients.
AB  - OBJECTIVES: Context processing is the adaptive control of current behavior
      through the use of prior context information. It has been found to be impaired in
      schizophrenia. Some studies have indicated that, compared with patients with
      schizophrenia, those with bipolar disorder (BPD) display a similar but less
      severe neuropsychological pattern of impairment. However, this cognitive
      dimension has not yet been examined in BPD patients in the existing literature.
      METHODS: An expectancy version of the AX continuous performance test (AX-CPT) was
      administered to 15 bipolar outpatients and 26 healthy controls. Patients with
      schizophrenia, in which context processing deficits are known to occur, were used
      as a reference group. RESULTS: Bipolar patients showed a context processing
      deficit relative to healthy controls, although this was less severe and
      generalized than in schizophrenia patients. CONCLUSIONS: These findings suggest
      there are milder impairments in context processing in BPD compared with
      schizophrenia. However, the severity of possible context processing deficits in
      BPD may have been underestimated in our sample of mostly euthymic outpatients.

PMID- 17430298
TI  - Changes in insight among patients with bipolar I disorder: a 2-year prospective
      study.
AB  - OBJECTIVES: The aim of this 2-year prospective study was to examine changes in
      insight among bipolar patients with different clinical courses. METHODS: A cohort
      of 65 patients with bipolar I disorder in remission was recruited for this study.
      They received six follow-up assessments over a 2-year period. The Schedule of
      Assessment of Insight-Expanded version (SAI-E) was used to determine their levels
      of insight, while the Young Mania Rating Scale (YMRS) and the Hamilton Rating
      Scale for Depression (HAM-D) were used to determine affective symptoms. Types of
      changes in insight among bipolar patients were analyzed according to the
      different clinical courses during the 2-year follow-up period. RESULTS: Insight
      in consistently stable patients was steady during the 2-year period. Insight
      decreased during the manic period in patients with only a single manic episode as
      well as in those with repeated manic episodes. However, insight returned to the
      pre-episode level for patients with only a single manic episode, but did not for
      most of the patients with repeated episodes. No changes in insight were observed
      during depressive episodes for either patients with a single or those with
      repeated depressive episodes. CONCLUSIONS: The types of insight changes among
      bipolar patients during the 2-year period were various and depended on the
      different clinical courses. Frequent mood disturbance episodes may cause patient
      insight to deteriorate.

PMID- 17430299
TI  - Differentiating bipolar disorder in Turkish prepubertal children with attention
      deficit hyperactivity disorder.
AB  - BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) and bipolar disorder
      (BPD) in children are frequently comorbid conditions. Because the coexistence of
      ADHD and mania seriously complicates the course of the condition and the
      treatment of children, diagnosing or missing this comorbidity has important
      clinical implications. There are very few systematic studies on the subject in
      the literature and BPD in children is not recognized or studied in most countries
      other than the USA. We aimed to differentiate Turkish prepubertal children with
      ADHD from those with comorbid ADHD and BPD and compare their clinical
      characteristics. METHODS: A total of 147 treatment- and drug-naive children, aged
      7 to 13 years, who had been consecutively referred to the ADHD clinic, were
      evaluated using the Schedule for Affective Disorders and Schizophrenia for School
      age Children-Present and Lifetime version (K-SADS-PL). Parents completed the
      Child Behavior Checklist (CBCL) 4-18 and the Parent-Young Mania Rating Scale (P
      YMRS) prior to the clinical interview. RESULTS: Twelve children (8.2%) had
      comorbid bipolar disorder (ADHD + BPD). The ADHD + BPD group had significantly
      higher rates of depressive disorders, oppositional defiant disorder, panic
      disorder and a family history of bipolar disorder compared with the ADHD group.
      The ADHD + BPD group had significantly more problems on the CBCL scale
      (anxiety/depression, social problems, thought problems, aggression,
      externalization, and total score) and on the P-YMRS (all items except for
      insight) compared with the ADHD group. CONCLUSIONS: We conclude that ADHD + BPD
      in Turkish children represents a clinical picture different to that of ADHD
      alone, in which the clinical characteristics resemble those of children reported
      in the literature. Further long-term follow-up studies are needed in larger
      clinical and community samples.

PMID- 17430300
TI  - Hospitalization risks in the treatment of bipolar disorder: comparison of
      antipsychotic medications.
AB  - OBJECTIVES: This study compared the relative risk for hospitalization of patients
      with bipolar and manic disorders receiving atypical and typical antipsychotics.
      METHODS: This retrospective study was based on administrative claims data
      extracted from the PharMetrics database during 1999 through 2003. Comparisons
      were made among atypical antipsychotics (risperidone, olanzapine, quetiapine or
      ziprasidone), as well as between each of these versus a combined group of the
      leading typical antipsychotics. Relative risk for hospitalization was estimated
      with Cox proportional regression, which adjusted for differences in patient
      characteristics. RESULTS: Risperidone and olanzapine demonstrated higher risks
      for hospitalization than quetiapine [hazard ratio (HR) 1.19, p < 0.05 for both],
      translating into higher annual mental health inpatient charges of $260 per
      patient. Risperidone and olanzapine also showed higher estimated risks than
      ziprasidone, which approached the p < 0.05 threshold. Differences between each of
      the atypicals and the combined typicals were not significant. Patients with
      putative rapid cycling had a threefold greater risk for hospitalization than
      other patients with bipolar disorder. In these patients, comparisons among
      atypical antipsychotics showed that risperidone had a significantly higher
      hospitalization risk than olanzapine (HR 3.31, p < 0.05), resulting in higher
      annual mental health inpatient charges of $4,930 per patient. CONCLUSIONS: In the
      treatment of bipolar and manic disorders, risperidone and olanzapine were
      associated with a higher risk for hospitalization than quetiapine, and possibly
      ziprasidone. In the treatment of putative rapid cyclers, olanzapine was
      associated with a lower risk for hospitalization than risperidone.

PMID- 17430301
TI  - Prevalence and correlates of burden among caregivers of patients with bipolar
      disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar
      Disorder.
AB  - OBJECTIVES: Caring for a relative with schizophrenia or dementia is associated
      with reports of high caregiver burden, symptoms of depression, poor physical
      health, negligence of the caregiver's own health needs, elevated health service
      use, low use of social supports, and financial strain. This study presents the
      design and preliminary data on the costs and consequences of caring for a
      relative or friend with bipolar disorder from the Family Experience Study, a
      longitudinal study of the primary caregivers to 500 patients enrolled in the
      Systematic Treatment Enhancement Program for Bipolar Disorder. METHODS: Subjects
      were primary caregivers of 500 patients with bipolar disorder diagnosed by the
      Mini International Neuropsychiatric Interview and the Affective Disorder
      Evaluation. Caregivers were evaluated within 1 month after patients entered
      Systematic Treatment Enhancement Program using measures of burden, coping,
      health/mental health, and use of resources and costs. RESULTS: Eighty-nine
      percent, 52%, and 61% of caregivers, respectively, experienced moderate or higher
      burden in relation to patient problem behaviors, role dysfunction, or disruption
      of household routine. High burden caregivers reported more physical health
      problems, depressive symptoms, health risk behavior and health service use, and
      less social support than less burden caregivers. They also provided more
      financial support to their bipolar relative. CONCLUSIONS: Burdens experienced by
      family caregivers of people with bipolar disorder are associated with problems in
      health, mental health, and cost. Psychosocial interventions targeting the strains
      of caregiving for a patient with bipolar disorder are needed.

PMID- 17430302
TI  - The occurrence of cavum septi pellucidi enlargement is increased in bipolar
      disorder patients.
AB  - OBJECTIVES: This study was conducted to evaluate the prevalence of cavum septi
      pellucidi (CSP) enlargement in patients with bipolar disorder (BD) and healthy
      comparison subjects. METHODS: The occurrence of enlarged CSP in patients with BD
      (n = 41, age 35.4 +/- 10.8 years) and healthy volunteers (n = 41, age 35.3 +/-
      10.0 years) was studied using magnetic resonance imaging. The length of the CSP
      was measured by counting the number of consecutive resliced coronal 0.5-mm images
      in which the CSP was present. A CSP length > or = 6 mm was a priori defined as
      abnormal enlargement of the CSP. RESULTS: Bipolar subjects exhibited a
      significantly higher prevalence of abnormal CSP enlargement (8 of 41 subjects,
      19.5%) than healthy comparison subjects (1 of 41 subjects, 2.4%) (logistic
      regression analysis: Wald statistic = 5.07, df = 1, p = 0.024). The prevalence of
      abnormally enlarged CSP was not significantly different between drug-naive and
      drug-exposed bipolar subjects or when comparing bipolar I and II sub-diagnoses.
      Bipolar subjects with abnormal CSP enlargement had a significantly earlier onset
      of BD than those without (14.3 +/- 3.6 versus 20.1 +/- 7.4 years, respectively).
      CONCLUSIONS: The current study is the first to report an increased prevalence of
      abnormally enlarged CSP in a well-characterized bipolar population. Our finding
      that an abnormal enlargement of CSP, a neurodevelopmental abnormality, is
      associated with early onset of illness implicates early maturational processes as
      contributing to BD.

PMID- 17430303
TI  - Specificity of mood stabilizer action on neuronal growth cones.
AB  - OBJECTIVES: Lithium, valproic acid (VPA) and carbamazepine (CBZ) are commonly
      used mood stabilizers, but their therapeutic mechanism is unclear. These drugs
      all cause the same morphological effects on postnatal rat neuronal dorsal root
      ganglia (DRG) growth cones via an inositol-reversible mechanism. However, due to
      limitations in earlier analysis, the effects of combining drugs, drug specificity
      and inositol stereoisomer specificity are unknown. We devised an improved
      analytical method to address these issues. METHODS: Dorsal root ganglia explants
      were cultured individually and incubated with combinations of psychotropic drugs
      and inositol stereoisomers. We recorded axonal growth cone morphology and
      calculated growth cone area per a modified method described by Williams et al.
      (Nature 2002; 417: 292-295). Statistically significant changes in area were
      calculated using non-parametric statistical testing. RESULTS: (i) Lithium and VPA
      showed an additive effect on growth cone spreading. (ii) Among eight additional
      psychotropic drugs to those previously tested, only imipramine and chlorpromazine
      altered DRG growth cone morphology. As this effect was not reversed by myo
      inositol, it arises from a different mechanism to the mood stabilizers lithium,
      VPA and CBZ. (iii) Myo-inositol, but not scyllo- or epi-inositol, causes a
      significant reversal of the lithium effect on the growth cones spreading,
      consistent with the inositol depletion hypothesis. CONCLUSIONS: These results
      show that lithium, VPA and CBZ are unique in causing altered neuronal morphology
      via myo-inositol depletion.

PMID- 17430304
TI  - Effects of mood stabilizers on the inhibition of adenylate cyclase via dopamine
      D(2)-like receptors.
AB  - OBJECTIVE: The mood stabilizing drugs lithium, carbamazepine and valproate
      modulate brain adenosine monophosphate (cAMP) levels, which are assumed to be
      elevated in bipolar disorder patients. The aim of this work was to investigate
      how these three mood stabilizing agents affect the regulation of cAMP levels by
      dopamine D(2)-like receptors in vitro in rat cortical neurons in culture and in
      vivo in the rat prefrontal cortex. METHODS: The production of cAMP was measured
      in the cultured cortical neurons or in microdialysis samples collected from the
      prefrontal cortex of freely moving rats using the [8-(3)H] and [(125)I]
      radioimmunoassay kits. RESULTS: In vitro and in vivo data showed that the
      treatment with the mood stabilizing drugs had no effect on basal cAMP levels in
      vitro, but had differential effects in vivo. Direct stimulation of adenylate
      cyclase (AC) with forskolin increased cAMP levels both in vitro and in vivo, and
      this effect was significantly inhibited by all three mood stabilizers. Activation
      of dopamine D(2)-like receptors with quinpirole partially inhibited forskolin
      induced increase in cAMP in untreated cultures, but no effect was observed in
      cortical neuron cultures treated with the mood stabilizing drugs. Similar results
      were obtained by chronic treatment with lithium and valproate in the prefrontal
      cortex in vivo. However, surprisingly, in carbamazepine-treated rats the
      activation of dopamine D(2)-like receptors enhanced the responsiveness of AC to
      subsequent activation by forskolin, possibly as a consequence of chronic
      inhibition of the activity of the enzyme. CONCLUSIONS: It was shown that each of
      these drugs affects basal- and forskolin-evoked cAMP levels in a distinct way,
      resulting in differential responses to dopamine D(2)-like receptors activation.

PMID- 17430305
TI  - Lithium normalizes elevated intracellular sodium.
AB  - BACKGROUND: Both mania and bipolar depression are characterized by elevations of
      intracellular sodium concentrations. This observation has been purported to be
      central to the pathophysiology of abnormal moods in bipolar illness. Reduction of
      sodium influx is a proposed shared mechanism of action of effective mood
      stabilizers, but direct documentation of this effect for lithium has never been
      demonstrated. METHODS: Flame spectroscopic determinations of intracellular sodium
      concentration were performed in the human glioma cell line, LN292, after
      treatment with the sodium pump inhibitor, ouabain, and co-treatment with ouabain
      and lithium. RESULTS: Ouabain 0.1 microM doubles the intracellular sodium
      concentration after 3 days. Pretreatment with lithium 1 mM for 1 week normalizes
      intracellular sodium. CONCLUSION: This is the first demonstration that lithium
      can normalize abnormally elevated intracellular sodium levels. This may be an
      important mechanism of lithium action.

PMID- 17430306
TI  - Age and ratings of manic psychopathology.
AB  - OBJECTIVES: Clinicians have suggested that manic psychopathology in adulthood
      changes with advanced age. We used rating scale evaluations of manic
      psychopathology in adult patients with bipolar (BP) disorder to test whether
      older age is associated with scores on items related to excesses of behaviors:
      i.e., Sexual Interest, Increased Activity-Energy, Speech--Rate and Amount, and
      Disruptive-Aggressive Behavior. METHODS: The association of Young Mania Rating
      Scale item scores with current age was studied in symptomatic inpatients meeting
      DSM-IV criteria for BP disorder, manic. RESULTS: The sample consisted of 149
      patients ranging in age from 18 to 89 years; 48 of these were male. Age was not
      associated with differences in overall severity reflected in total score. Age was
      associated with lower scores on the Sexual Interest item (r = - 0.26, p < 0.001).
      A trend for higher scores with age on Speech--Rate and Amount (r = 0.19, p <
      0.02) did not meet criteria for significance. Increased Activity-Energy,
      Disruptive-Aggressive Behavior and other item scores were not associated with
      age. In an exploratory analysis, age and Sexual Interest and Speech item scores
      were associated in female patients but not in male patients. CONCLUSIONS: These
      findings suggest that age minimally influences manic psychopathology in patients
      with BP disorder. The modest correlation between age and Sexual Interest item
      scores warrants further investigation and the trend for an association between
      age and Speech--Rate and Amount can be examined in future studies. Possible
      gender differences in the associations between age and these item scores also
      invite future study.

PMID- 17430307
TI  - Adverse pregnancy outcomes in mothers with affective psychosis.
AB  - OBJECTIVES: Affective psychosis has its peak incidence during the childbearing
      years, but little is known about the effects of the illness on pregnancy. We
      investigated risks of preterm delivery (PTD), low birthweight (LBW), births of
      infants small for their gestational age (SGA), stillbirth and infant death in
      births to mothers with affective psychosis using a nested case-control design
      within a cohort of 1,558,071 singleton births in Sweden during 1983-1997.
      METHODS: Using prospectively collected data from population registers, we
      compared the pregnancy outcomes of 5,618 births to women with affective psychosis
      with the outcomes of 46,246 births to unaffected mothers. RESULTS: Mothers with
      affective psychosis had elevated risk for giving birth to preterm, small or
      growth-retarded babies. The risk for stillbirth and infant death during the first
      year of life was not significantly higher. The risks were greatest in mothers
      receiving hospital treatment for affective disorder during pregnancy: (i) preterm
      delivery: odds ratio (OR) = 2.67, 95% confidence interval (CI) = 1.71-4.17; (ii)
      SGA: OR = 2.36; 95% CI = 1.34-4.16; (iii) low birthweight: OR = 2.22; 95% CI =
      1.31-3.76; and (iv) stillbirth: OR = 2.19; 95% CI = 0.55-8.76. After adjustment
      for covariates, particularly smoking, the risks were attenuated but remained
      significant. CONCLUSIONS: Clinicians should be aware of the increased risk of
      adverse pregnancy outcomes in women with affective psychosis, some of which may
      be preventable.

PMID- 17430308
TI  - Two case reports of oral ulcers with lamotrigine several weeks after
      oxcarbazepine withdrawal.
AB  - OBJECTIVE: To report two cases of mouth ulcers in lamotrigine patients after
      oxcarbazepine withdrawal. PATIENTS AND METHODS: The first patient was a 35-year
      old woman with bipolar disorder II (BD II) started on lamotrigine and tapered off
      oxcarbazepine while an inpatient. The second patient was a 36-year-old man with
      BD II. He was discharged on lamotrigine and oxcarbazepine with the recommendation
      of a slow withdrawal of oxcarbazepine. RESULTS: Many weeks after hospital
      discharge and after a stable lamotrigine dose had been established, both patients
      developed painful mouth ulcers that were diagnosed during outpatient visits. The
      first patient developed ulcers 39 days after oxcarbazepine was stopped and the
      ulcers resolved 4 days after lamotrigine discontinuation. The second patient was
      taking 1200 mg/day of oxcarbazepine and after leaving hospital decreased this to
      600 mg/day. Twenty-two days after the oxcarbazepine decrease, he developed oral
      ulcers that resolved with oxcarbazepine and lamotrigine discontinuation.
      CONCLUSIONS: Lamotrigine is mainly metabolized by glucuronidation, specifically
      by the uridine 5'-diphosphate glucuronosyltransferases 1A4 (UGT1A4).
      Carbamazepine is a UGT1A4 inducer. These two cases suggest that oxcarbazepine may
      also induce lamotrigine metabolism. The discontinuation or dosage decrease of
      carbamazepine or oxcarbazepine may be associated with a slow increase of
      lamotrigine levels over several weeks and thus increase risk of lamotrigine
      toxicity that may manifest as oral ulcers. Hospital psychiatrists need to be
      aware that discontinuation of inducers may take several weeks to manifest as side
      effects.

PMID- 17430310
TI  - Intensive care in the very old: are we prepared?

PMID- 17430311
TI  - Intensive care of the elderly in Finland.
AB  - BACKGROUND: The ageing of the population will increase the demand for health care
      resources. The aim of this study was to determine how age affects resource
      consumption and outcome of intensive care in Finland. METHODS: Data on 79,361
      admissions to 26 Finnish intensive care units (ICUs) during the years 1998-2004
      were analysed. The severity of illness was measured using Simplified Acute
      Physiology II scores and the intensity of care using Therapeutic Intervention
      Scoring System scores. RESULTS: The median age was 62 years; 8.9% of patients
      were aged 80 years or over. The hospital mortality rate was 16.2% in the overall
      patient population, but 28.4% in patients aged 80 years or over. Old age was an
      independent risk factor for hospital mortality. The mean intensity of care was at
      its highest in the age groups 60-69, 70-74 and 75-79 years. It was notably lower
      for patients aged 80 years or over. If the need for intensive care remains
      unchanged in each age group, the change in the age distribution of the Finnish
      population will increase the demand for ICU beds by 19% by the year 2020 and by
      25% by the year 2030. CONCLUSION: The hospital mortality rate increases with
      increasing age. The mean intensity of care is lower for the oldest patients than
      for patients aged less than 80 years. The ageing of the population will probably
      cause a remarkable increase in the need for intensive care in the near future.

PMID- 17430312
TI  - Long-term outcome of elderly patients requiring intensive care admission for
      abdominal pathologies: survival and quality of life.
AB  - BACKGROUND: Medical developments have allowed the management of patients aged
      over 70 years with severe abdominal pathologies requiring intensive care unit
      (ICU) admission. These patients require enhanced life support and present a high
      ICU mortality. We investigated the outcome and quality of life (QOL) of elderly
      patients 2 years after their ICU stay for abdominal pathologies. METHODS:
      Patients aged 70 years or over with abdominal pathologies, admitted to our ICU
      over a period of 2 years, were included. Two years following their ICU stay, a
      letter informed the patients about the present study. Consent to participate was
      obtained by telephone. QOL was assessed by the Euro-QOL and Short Form-36
      questionnaires. Other patient-centered outcomes were evaluated. RESULTS: Overall,
      2780 patients were admitted to the ICU during the study period; 141 (5%) patients
      were eligible; 112 of the 141 (79%) survived their ICU stay, 95 (67%) survived
      their hospital stay and 52 (37%) were alive 2 years after their ICU stay; 36 of
      the 52 survivors (69%) answered the questionnaire. Their QOL 2 years after their
      ICU stay was decreased in comparison with an age-matched population. Eighty-one
      per cent of patients lived at home and 57% were totally independent. They
      perceived their ICU stay as positive and 75% stated that they would agree to go
      through intensive care again. Factors associated with 2-year survival were the
      absence of co-morbidity, absence of malignancy and a lower Simplified Acute
      Physiology II score on ICU admission. CONCLUSIONS: A high mortality rate and a
      decrease in QOL were observed in elderly patients with severe abdominal
      pathologies. Nonetheless, these patients were able to adapt well to their
      physical disabilities.

PMID- 17430313
TI  - Stroke volume variation during hemorrhage and after fluid loading: impact of
      different tidal volumes.
AB  - BACKGROUND: Previous studies have shown that stroke volume variation (SVV) may be
      used to assess preload and fluid responsiveness. It is currently under debate, if
      SVV reliably displays changes in preload during ventilation with clinically used
      tidal volumes. This study was designed to evaluate whether the predictive value
      of SVV depends on the tidal volume applied particularly during acute changes of
      preload. METHODS: We studied 14 anesthetized pigs (35 +/- 2 kg) during changing
      tidal volumes (5, 10 and 15 ml/kg) at normovolemia (BL), after removal of 500 cc
      of blood (Hypo) and after retransfusion plus additional 500 cc 6% hydroxyethyl
      starch (Hyper). SVV was recorded continuously, and global end-diastolic volume
      (GEDV) was obtained by transpulmonary thermodilution at each experimental stage.
      RESULTS: GEDV changed significantly comparing the different experimental stages
      (P < 0.0001). During ventilation with 5 ml/kg, SVV did not change significantly
      at the different loading conditions. In contrast, during ventilation with both 10
      and 15 ml/kg, SVV changed significantly comparing hemorrhage to fluid loading.
      However, at 15 ml/kg SVV was above the recommended value throughout the
      experiment. CONCLUSIONS: In this animal model, SVV was not sensitive to acute
      changes in preload during ventilation with a tidal volume of 5 ml/kg. Moreover,
      ventilation with high tidal volume may suggest volume loading even after
      sufficient volume resuscitation.

PMID- 17430314
TI  - Beat-to-beat change in "myocardial performance index" related to load.
AB  - BACKGROUND: This study was designed to assess the relationship of the "myocardial
      performance index" (MPI) to the beat-by-beat change in pre-load with static or
      unchanged contractile status. METHODS: Eight anesthetized juvenile pigs were
      studied using direct measurement of the left ventricular pressure and volume.
      Transient inflation of a vena cava balloon catheter produced controlled pre-load
      alterations. Consecutive beats were analyzed, grouped for first, second, third,
      etc. during the pre-load alteration, and evaluated for the change in MPI during
      the same contractile status with a controlled pre-load alteration. Two
      pharmacologic inotropic interventions were also included to generate several
      myocardial conditions in each animal. RESULTS: MPI demonstrated a strong linear
      relationship to the pre-load and after-load. MPI increased progressively during
      decreasing end-diastolic volume, mostly related to changes in ejection time. MPI
      was observed at the same level for three different myocardial function conditions
      (all eight animals), with a different relationship between MPI and pre-load noted
      for each observation. CONCLUSIONS: MPI is strongly load dependent, and can vary
      widely in value for the same contractile status if the load is varied. The use of
      this index in critically ill patients should be limited in this respect. Further
      work is needed to establish the relationship of MPI to load and contractile
      status.

PMID- 17430315
TI  - The effect of combining intermittent hemodiafiltration with forced alkaline
      diuresis on plasma myoglobin in rhabdomyolysis.
AB  - BACKGROUND: Our aim was to examine the effect of combining intermittent
      hemodiafiltration (HDF) with forced alkaline diuresis on plasma myoglobin in
      rhabdomyolysis. METHODS: This was a prospective, randomized, controlled, cross
      over study. Sixteen rhabdomyolysis patients with plasma myoglobin concentrations
      above 10,000 microg/l were randomized. Forced alkaline diuresis was started
      immediately after allocation and continued throughout the study. HDF, which
      lasted for 4 h, was started in group A immediately after allocation and in group
      B 4 h later. The primary analysis was intention-to-treat by repeated measures
      analysis of variance and Mann-Whitney U-test. RESULTS: The percentage elimination
      of myoglobin from the circulation during HDF differed significantly from that
      during alkaline diuresis (28.1% vs. 14.2%, respectively; P < 0.01). The mean
      decrease in plasma myoglobin concentration during HDF [9731 microg/l; 95%
      confidence interval (CI), 3672-5345 microg/l] and forced alkaline diuresis (3646
      microg/l; 95% CI, 1260-6032 microg/l) did not show a statistically significant
      difference (P= NS). The mean total amount of myoglobin found in the ultrafiltrate
      was 58.4 mg. CONCLUSION: The percentage myoglobin decrease during combined HDF
      and forced alkaline diuresis was higher than that during forced alkaline diuresis
      alone. Renal replacement therapy with filtration techniques may be considered for
      the clearance of myoglobin from plasma when urine alkalinization is not
      successful.

PMID- 17430316
TI  - Low concentrations of inhaled nitric oxide do not improve oxygenation in patients
      with very severe chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by
      airway narrowing that is most frequently inhomogeneously distributed.
      Ventilation/perfusion (V/Q) mismatch may explain much of the hypoxemia in
      patients with advanced disease. A potential treatment strategy would be to
      redistribute blood flow to well-ventilated lung regions in order to decrease V/Q
      mismatch. It has been suggested that inhaled nitric oxide (iNO) in physiologic
      concentrations ( approximately 100 p.p.b.) could act as a local vasodilating
      agent in well-ventilated lung regions. To test this, we included 10 volunteer
      patients with very severe COPD in this study. METHODS: NO was mixed with O(2) and
      N(2) and administered through a face mask. The partial pressure of inspired
      oxygen (P(i)o(2)) did not change by more than +/- 0.5 kPa from the room air
      value. NO was given in 15-min periods at concentrations of approximately 0,
      approximately 40, approximately 400, approximately 4000 and approximately 40,000
      p.p.b. (random order). During each NO exposure, arterial blood gases,
      methemoglobin and systemic blood pressure were measured every fifth minute.
      RESULTS: None of the patients reported subjective effects of the different gas
      mixtures. The partial pressure of oxygen in arterial blood (P(a)o(2)) did not
      change by more than +/- 1.2 kPa from the baseline value, and there was no
      correlation between the change in P(a)o(2) and iNO concentration. No significant
      changes were found in blood pressure or methemoglobin during iNO. CONCLUSION: No
      significant effect of iNO at concentrations up to 40,000 p.p.b. in inspired gas
      was found on arterial blood gases. This indicates that neither low nor high
      concentrations of iNO improve oxygenation in patients with very severe COPD.

PMID- 17430317
TI  - Transfusion of red blood cells: no impact on length of hospital stay in
      moderately anaemic parturients.
AB  - BACKGROUND: In a search for information to improve decision making on red blood
      cell (RBC) transfusion, we examined the impact of RBC transfusion on the length
      of hospital stay for delivery in moderately anaemic women (haemoglobin, 7-10
      g/dl). METHODS: This was a retrospective, observational study covering 2 years
      (2002 and 2003), and included major blood-transfusing hospitals from four
      university and five central hospital districts managing 67.5% of Finnish in
      hospital deliveries. The impact of the transfusion of 1-2 RBC units vs. no
      transfusion on the length of hospital stay was evaluated for three different
      haemoglobin levels: 7-7.9, 8-8.9 and 9-10 g/dl. RESULTS: Of the 1954 moderately
      anaemic mothers in hospital for delivery, 13.3% were transfused with RBC. The
      mean length of hospital stay was 5.2 days vs. the average Finnish hospital
      delivery stay of 3.5 days. No differences in stay were found between patients
      with comparable anaemia transfused with 1-2 RBC units or none (at the three
      haemoglobin levels: P= 0.50, P= 0.07 and P= 0.54, respectively). The final
      haemoglobin value was higher (P < 0.001) in transfused patients. CONCLUSION: The
      duration of admission for delivery in moderately anaemic parturients was longer
      than the average length of hospital stay in Finnish parturients. However, 1-2 RBC
      units had no impact on the length of stay, suggesting that unnecessary RBCs are
      transfused after delivery. Thus, transfusion practices in obstetrics are not
      always optimal.

PMID- 17430318
TI  - Splanchnic blood flow and oxygen consumption: effects of enteral nutrition and
      dopexamine in the elderly cardiac surgery patient.
AB  - BACKGROUND: After cardiac surgery, patients are at risk of organ dysfunction
      because of decreased perfusion. Different measures have been used to increase the
      splanchnic blood flow. We compared the effects of enteral nutrition and
      dopexamine on the cardiac output, splanchnic blood flow and oxygen consumption.
      METHODS: Sixteen patients undergoing cardiac surgery were included. Indocyanine
      green extraction and thermodilution were used for repeated measurements of the
      splanchnic blood flow and cardiac output. On the first post-operative day,
      indocyanine green infusion was started. Patients were randomized to start with
      dopexamine (Dpx group) or enteral nutrition (EN group). After 180 min, both
      groups received a combination of dopexamine and enteral nutrition. Blood gases
      from the hepatic vein and pulmonary and radial arteries were analysed repeatedly.
      RESULTS: In the Dpx group, the cardiac index increased with dopexamine infusion,
      but not when enteral nutrition was added. In the EN group, enteral nutrition
      alone did not increase the cardiac index, but dopexamine addition increased the
      cardiac index in this group. The splanchnic blood flow increased initially in the
      Dpx group, but then returned to baseline and remained constant on addition of
      enteral nutrition. In the EN group, the splanchnic blood flow initially remained
      at baseline, but increased after dopexamine addition. There was no difference
      between the groups with regard to systemic or splanchnic oxygen consumption or
      the oxygen extraction ratio. In the Dpx group, lactate increased from baseline
      with no further increase on addition of enteral nutrition. Lactate was unchanged
      in the EN group. CONCLUSIONS: Dopexamine and enteral nutrition caused no adverse
      effects on oxygen consumption or the oxygen extraction ratio. Enteral nutrition
      did not increase the splanchnic blood flow or cardiac index. Dopexamine increased
      the systemic blood flow with only a transient effect on the splanchnic blood
      flow. Dopexamine increased the lactate concentration, possibly indicating a more
      ischaemic condition.

PMID- 17430319
TI  - Does the pre-ischaemic administration of sevoflurane reduce myocardial stunning?
      A porcine experimental model.
AB  - BACKGROUND: In a porcine model, the cardioprotective effect of sevoflurane was
      studied with regard to the preservation of myocardial contractility (myocardial
      stunning) after a myocardial ischaemic insult. METHODS: Twenty-seven pigs were
      randomized to receive either a dual 4% sevoflurane inhalation period as a
      supplement to pentobarbital anaesthesia or pentobarbital anaesthesia only before
      a 15-min ischaemic insult on the left anterior descending coronary artery. The
      ischaemic period was followed by 180 min of reperfusion. Myocardial contractility
      was assessed by myocardial sonomicrometry. RESULTS: A significant difference was
      found between the sevoflurane group and the control group at 5 min of
      reperfusion. However, subsequently, there was no overall difference between the
      two groups. CONCLUSION: Sevoflurane administered as a pre-ischaemic bolus does
      not provide long-term improvement of the myocardial contractility. However, it
      can be speculated that sevoflurane may induce an early improvement in
      contractility.

PMID- 17430320
TI  - Prediction of post-operative pain by an electrical pain stimulus.
AB  - BACKGROUND: Treatment of post-operative pain is still a significant problem.
      Recently, interest has focused on pre-operative identification of patients who
      may experience severe post-operative pain in order to offer a more aggressive
      analgesic treatment. The nociceptive stimulation methods have included heat
      injury and pressure algometry. A simple method, Pain Matcher (PM), using
      electrical stimulation, is validated for pain assessment, but has not been
      evaluated as a tool for prediction of post-operative pain. Our aim was to assess
      the predictive value of pre-caesarean section pain threshold on intensity of post
      caesarean section pain using the PM. PATIENTS AND METHODS: Thirty-nine healthy
      women scheduled for elective caesarean section were studied. The
      anaesthetic/analgesic procedures included spinal anaesthesia, paracetamol,
      diclofenac, controlled-release (CR) oxycodone and morphine on request. Pre
      operatively, the sensory and pain thresholds were measured using the PM. Post
      operatively, a midwife, blinded for pre-caesarean pain threshold assessments,
      assessed the pain at rest and during mobilization every 12 h for 2 days.
      Consumption of analgesics was also recorded. RESULTS: Pre-operative pain
      threshold correlated significantly with post-caesarean pain score (VAS) at rest
      and mobilization: [Spearman's rho =-0.65 (-0.30 to -0.75), P < 0.01] and
      [Spearman's rho =-0.52 (-0.23 to -0.72), P < 0.01], respectively. There was no
      significant correlation between pre-operative PM assessment of sensory threshold
      and post-operative pain. CONCLUSION: Electrical pain threshold before caesarean
      section seems to predict the intensity of post-operative pain. This method may be
      used as a screening tool to identify patients at high risk of post-operative
      pain.

PMID- 17430321
TI  - Effect of thoracic epidural analgesia on gastric blood flow after oesophagectomy.
AB  - BACKGROUND: The oesophagectomy procedure includes the formation of a gastric tube
      to re-establish the continuity of the gastrointestinal tract. The effect of
      thoracic epidural analgesia (TEA) on gastric mucosal blood flow (GMBF) remains
      unknown in clinical practice. The aim of this prospective observational study was
      to assess the microcirculatory changes induced by TEA in the early post-operative
      course. METHODS: Eighteen consecutive patients who underwent radical
      oesophagectomy with en-bloc resection and two-field lymphadenectomy for
      oesophageal cancer, and benefited from TEA during the post-operative course, were
      studied prospectively, and compared with nine patients who declined the use of
      TEA in the same period (control group). GMBF was measured using a laser Doppler
      flowmeter in three consecutive time periods (before and after 1 and 18 h of TEA
      infusion). Post-operative monitoring also included the measurement of arterial
      pressure, cardiac output, gas exchange and intrathoracic blood volume index.
      RESULTS: After the first and 18th hour of infusion, TEA induced an increase in
      GMBF compared with baseline and the control group. The mean arterial pressure and
      intrathoracic blood volume index decreased after the first hour of TEA infusion
      with no influence on the cardiac index. CONCLUSIONS: This clinical study
      demonstrates that TEA improves the microcirculation of the gastric tube in the
      early post-oesophagectomy period. The clinical relevance of TEA in this setting
      should be validated in larger studies focusing on the clinical outcome following
      oesophagectomy.

PMID- 17430322
TI  - Management of incomplete regional anaesthesia in Germany: results of a nation
      wide survey.
AB  - BACKGROUND: Regional anaesthesia (RA) provides well-defined benefits with known
      attendant risks. However, incomplete blockade may introduce unanticipated risks
      depending on the compensatory measures employed. Until now, no data were
      available characterizing the pattern of response of German anaesthesiologists in
      this situation. This study analyses interventions in response to incomplete RA in
      a nation-wide setting. METHODS: A questionnaire was sent to every German
      anaesthesia department (n= 1381). Questions focused on interventions coping with
      an incomplete RA and differentiated between a pre- and a peri-surgical setting
      and measures to face pain outside the surgical field. If systemic supplementation
      was administered, we analysed the substances and characterized their influence on
      subsequent patient care. RESULTS: Six hundred and sixty-seven questionnaires were
      returned anonymously, representing a return rate of 48.3%. If RA was incomplete
      before surgery, 56.8% of anaesthesiologists repeated peripheral blocks, 48.5%
      repeated epidural (EDA) and 60.4% repeated spinal anaesthesia (SPA). 56.9% of
      clinicians preferred an early switch to general anesthesia (GA). If RA was
      incomplete during surgery, 49.5% tended to switch early to GA, 13.9% made
      attempts to avoid this by intensive systemic supplementation. Benzodiazepines and
      opioids were the most commonly used substances. Pain or discomfort outside the
      surgical field was widely managed by intravenous supplementation (67.7%) and only
      10.6% were willing to switch to general anaesthesia. CONCLUSIONS: In Germany,
      anaesthesiologists manage incomplete RA using a widespread spectrum of measures.
      Some might introduce specific risks, which potentially outweigh the benefits of
      RA in comparison to GA techniques.

PMID- 17430323
TI  - The effects of single-dose tramadol on post-operative pain and morphine
      requirements after coronary artery bypass surgery.
AB  - AIM: To investigate the effects of a single dose of tramadol administered prior
      to extubation on post-operative pain and morphine consumption after coronary
      artery bypass surgery. METHODS: Patients were randomized post-operatively into
      two groups (group T, n= 30; group P, n= 30). The technique of anaesthesia was
      standardized for all patients. The patients in group T received intravenous
      tramadol, 1 mg/kg, and the patients in group P received 2 ml of saline 0.9%, both
      approximately 1 h before extubation. After extubation, all patients were allowed
      to use the morphine patient-controlled analgesia (PCA) device for 24 h post
      operatively. Post-operative data were recorded in the cardiac intensive care unit
      at 30 min, 1 h, 2 h, 4 h, 12 h and 24 h after extubation by the same
      anaesthesiologist, who had no knowledge of the groups, and the side-effects were
      also evaluated. RESULTS: In group P, the visual analogue scale (VAS) scores were
      found to be higher 30 min (P < 0.01), 1 h (P < 0.01), 2 h (P < 0.01) and 4 h (P <
      0.05) after extubation. The patient comfort scores were higher in group T 30 min
      (P < 0.01), 1 h (P < 0.05), 2 h (P < 0.01) and 4 h (P < 0.01) after extubation.
      The total morphine consumption was higher in group P at all evaluation times (P <
      0.01), and the numbers of PCA demands and boluses were also higher in group P (P
      < 0.01). CONCLUSIONS: The study demonstrated that a single dose of tramadol
      administered prior to extubation following coronary artery bypass surgery is
      associated with a decrease of up to 25% in morphine consumption, a decrease in
      the VAS scores and an improvement in patient comfort within the first 4 h post
      operatively.

PMID- 17430324
TI  - Dose effect of sevoflurane and isoflurane anesthetics on cortical blood flow
      during controlled hypotension in the pig.
AB  - BACKGROUND: The ability of the brain to preserve adequate cerebral blood flow
      (CBF) during alterations in systemic perfusion pressure is of fundamental
      importance. At increasing concentrations, isoflurane and sevoflurane have been
      known to alter CBF, which may be disadvantageous for patients with increased
      intracranial pressure. The aim was to examine the effects of isoflurane and
      sevoflurane at increasing minimum alveolar concentrations (MAC) on CBF, during
      controlled hypotension. METHODS: We studied eight pigs during variations in
      perfusion pressure induced by caval block (100, 60, 50, and 40 mmHg) under
      normocapnia. CBF was measured locally in a defined area (4 x 5 measurement points
      covering 1 cm(2)) of the motor cortex using laser Doppler perfusion imaging.
      Physiological variables, assessed by analysis of arterial O(2) and CO(2),
      hemoglobin and hematocrit, were controlled. CBF was measured during propofol (10
      mg x kg(-1)x h(-1)) and fentanyl (0.002 mg x kg(-1)x h(-1)) anesthesia, and then
      during anesthesia with either isoflurane or sevoflurane (given in random order)
      at increasing MAC (0.3-1.2). After a washout period, the measurements were
      repeated with the other gas. RESULTS: CBF was significantly higher in the cortex
      during normotensive (control) settings, MAP approximately 100 mmHg, compared with
      during hypotension (MAP 40-60 mmHg). Neither different anesthetic nor MAC or
      local measurement sites were found to influence CBF at any perfusion pressure.
      CONCLUSION: In this experimental model, the effect of hypotension on CBF was not
      altered by the anesthetics used [isoflurane, sevoflurane (MAC 0.3-1.2) or
      propofol (10 mg x kg(-1)x h(-1))]. In this aspect (cortical tissue perspective),
      these volatile agents appear as suitable as propofol for neurosurgical anesthesia
      for patients at risk.

PMID- 17430325
TI  - Male preponderance of patients testing positive for malignant hyperthermia
      susceptibility.
AB  - BACKGROUND: Malignant hyperthermia susceptibility is diagnosed using an in vitro
      contracture test (IVCT). In families in which the mutation is known, genetic
      tests are also available. The inheritance pattern is regarded as autosomal
      dominant, which predicts equal proportions of men and women affected. The aim of
      this study was to investigate whether there were sex differences in the
      diagnostic outcome of the 1407 patients tested for malignant hyperthermia in
      Sweden between 1985 and 2005. METHODS: Information about sex, diagnosis, IVCT
      result and kinship was analysed. Comparisons were made between the two sexes.
      Probands and relatives were analysed separately in order to eliminate bias caused
      by the type of surgery performed in the two sexes. RESULTS: Males, more than
      females, revealed a pathological outcome in IVCT. Amongst male relatives, the
      fraction of pathological outcome in IVCT was 0.70 [95% confidence interval (CI),
      0.66-0.74]; the corresponding value for females was 0.40 (95% CI, 0.36-0.44).
      CONCLUSION: A significant difference was observed in the sex distribution of
      outcome of IVCT, with significantly more males revealing a pathological IVCT.
      This indicates the influence of one or several factors related to sex in the
      outcome of IVCT, for example different expression of calcium handling proteins in
      the sexes, a complex pattern of inheritance or unknown environmental factors.

PMID- 17430326
TI  - Superior anti-emetic efficacy of granisetron-dexamethasone combination in
      children undergoing middle ear surgery.
AB  - AIM: To compare the effectiveness of granisetron and a granisetron-dexamethasone
      combination for the prevention of post-operative vomiting in children undergoing
      middle ear surgery. METHODS: Ninety ASA physical status I or II children, aged 3
      12 years, were randomly assigned to three groups of 30 each to receive a single
      dose of placebo (normal saline), granisetron 40 microg/kg or a combination of
      granisetron 40 microg/kg and dexamethasone 150 microg/kg intravenously after the
      induction of anaesthesia. Peri-operative anaesthetic care was standardized in all
      children. Post-operatively, during the first 24 h after anaesthesia, the
      frequencies of retching and vomiting and the incidence of adverse events were
      recorded. Rescue anti-emetic was administered if two or more episodes of emesis
      occurred. Post-operative pain was treated with morphine intravenously, followed
      by acetaminophen orally. RESULTS: There were no differences between the treatment
      groups with regard to demographic data. A complete response (no retching/vomiting
      and no need for rescue anti-emetic) was achieved in 50%, 80% and 96.67% of
      children who received saline, granisetron and granisetron-dexamethasone,
      respectively (P < 0.05). Six children who received placebo and one who received
      granisetron alone required another rescue anti-emetic. The incidence of adverse
      events was comparable in the three groups. CONCLUSION: The prophylactic
      granisetron-dexamethasone combination was more effective than granisetron alone
      in the prevention of post-operative emesis during the first 24 h after
      anaesthesia in children undergoing middle ear surgery.

PMID- 17430327
TI  - Compound A, formaldehyde and methanol concentrations during low-flow sevoflurane
      anaesthesia: comparison of three carbon dioxide absorbers.
AB  - AIM: To determine compound A, formaldehyde and methanol concentrations in low
      flow anaesthesia using different carbon dioxide absorbers. METHODS: Fifteen
      patients scheduled for general or urological surgery were exposed to low-flow
      (500 ml/min) anaesthesia with sevoflurane. The patients were randomly allocated
      to three groups: soda lime, DragerSorb Free or Amsorb Plus. The concentrations of
      compound A, formaldehyde and methanol were sampled and analysed from the limbs of
      the anaesthesia circuit at T30 (30 min after the start of low-flow sevoflurane
      anaesthesia), T90 (90 min) and T150 (150 min). The temperatures of the absorbers
      were measured at the same time. RESULTS: Statistically significant differences (P
      < 0.05) were found in the production of compound A from soda lime (with the
      highest values), DragerSorb Free and Amsorb Plus at each measurement time. Only
      traces of methanol (ranging from < 0.131 to 3.799 mg/m(3)) were measured, higher
      with Amsorb Plus (statistically significant differences were found only at T90).
      The formaldehyde values (ranging from < 0.1227 to 17.79 mcg/m(3) p.p.b.) were
      higher with soda lime, and the difference was statistically significant at T150
      and, in the inspiratory limb only, at T90. The temperatures of the absorbers were
      higher for soda lime and lower for Amsorb Plus; the difference was statistically
      significant at T0 in the upper canister and at T30 in both canisters. CONCLUSION:
      The concentrations of harmful products in the circuit were negligible and were
      lower using the new-generation absorbers. Using Amsorb Plus, the temperatures in
      the canisters were lower than with the other two absorbers.

PMID- 17430328
TI  - Management of persistent post-dural puncture headache after repeated epidural
      blood patch.
AB  - We report a case of persistent post-dural puncture headache (PDPH) in a patient
      despite two epidural blood patches (EBPs). Successful resolution of headache was
      achieved with a third EBP performed under computed tomography (CT) guidance. A 38
      year-old female had a total abdominal hysterectomy under combined spinal-epidural
      anesthesia with no complications. After surgery, she developed a postural
      headache consistent with PDPH. The first EBP was performed by injecting
      autologous blood through the epidural catheter that was in situ. The second EBP
      was performed under fluoroscopy. The patient continued to have a persistent
      headache. A computed tomography (CT) myelogram demonstrated cerebrospinal fluid
      (CSF) leak at L3-4 level. A "directed" CT-guided blood patch was then performed
      successfully with resolution of the headache.

PMID- 17430329
TI  - Anaesthetists should be aware of delayed hypersensitivity to phenylephrine.
AB  - Delayed reactions to phenylephrine, used as a mydriatic agent during
      ophthalmological surgical procedures, are well known. We diagnosed a delayed
      hypersensitivity reaction to phenylephrine included in an ophthalmic insert in a
      woman presenting, 24 h after surgery, with an acute blepharoconjunctivitis
      associated with eyelid eczema of the operated eye. The diagnosis was supported by
      the recognition of clinical symptoms associated with a positive patch test to
      phenylephrine. Patients who present with previous contact eczema to phenylephrine
      may develop a generalized eczema if phenylephrine is injected intravenously.
      Intravenous phenylephrine is increasingly being used in the operating room to
      treat hypotension. This case report confirms the need for systematic
      allergological investigation of all drugs and substances administered during the
      peri-operative period in order to avoid a delayed hypersensitivity reaction
      occurring after the peri-operative period. Anaesthetists should be aware of the
      possibility of delayed hypersensitivity reactions involving phenylephrine.

PMID- 17430330
TI  - Perioperative use of modified thrombelastography in factor XI deficiency: a
      helpful method to assess drug effects.
AB  - Factor XI deficiency is a rare, hereditary bleeding disorder associated with a
      trauma-related bleeding tendency, caused by insufficient generation of the
      thrombin activatable fibrinolysis inhibitor (TAFI) evoking increased
      fibrinolysis. We present the case of a five year old girl with homozygote, severe
      factor XI deficiency presenting for surgery on two occasions. Modified
      thrombelastography (ROTEM) was used to assess effects of factor XI deficiency on
      coagulation, endogenous fibrinolysis, and potential effects of tranexamic acid,
      aprotinin and recombinant, activated Factor VII in an in vitro model of
      hyperfibrinolysis. According to our data and in consideration of the mechanisms
      of factor XI deficiency we decided on prophylactic use of tranexamic acid.

PMID- 17430331
TI  - Mitral valve replacement under thoracic epidural anesthesia in an awake patient
      suffering from systemic sclerosis.

PMID- 17430332
TI  - The propofol infusion syndrome treated with haemofiltration. Is there a time for
      genetic screening?

PMID- 17430333
TI  - Repeated pulmonary oedema after interscalene block and general anaesthesia.

PMID- 17430334
TI  - Acute systemic contact dermatitis in a patient with nickel hypersensitivity:
      contamination from an intravenous catheter?

PMID- 17430335
TI  - Modified Allen's test performed with a pulse oximeter--back to the future?

PMID- 17430336
TI  - Proper utility of the nasogastric tube in assisting nasotracheal intubation.

PMID- 17430337
TI  - The immunodiagnosis of Echinococcus multilocularis infection.
AB  - Alveolar echinococcosis (AE) is a severe zoonotic disease caused by the
      metacestode stage of Echinococcus multilocularis. The infection can have fatal
      consequences in humans if treatment is not provided, so early diagnosis is
      fundamental for initiating treatment and reducing morbidity and mortality. In
      addition, detection of the parasite in the definitive host plays a central role
      in epidemiological studies and surveillance programmes for control of AE. This
      review presents an overview of the present situation regarding the
      immunodiagnosis of E. multilocularis infection. Special attention is given to the
      description of the native, partially purified and recombinant antigens available
      currently for immunodiagnostic purposes. Recent advances in the primary
      serodiagnosis and follow-up of AE patients are highlighted, including the
      detection of specific cytokine profiles. Progress in the immunodiagnosis of
      intestinal E. multilocularis infection in definitive hosts, particularly the
      detection of excretory-secretory and integument products of the worm in faeces
      (copro-antigens) by ELISA, is also discussed.

PMID- 17430338
TI  - Patterns and dynamics of airway colonisation in mechanically-ventilated patients.
AB  - The aim of this study was to investigate the patterns and dynamics of the
      microbiota in the airways of ventilated patients. Seventy-four mechanically
      ventilated patients were recruited consecutively, and oropharyngeal, tracheal and
      bronchoalveolar (BAL) fluid specimens were collected 48 h after intubation, and
      every 72 h thereafter until the patient was extubated or a total of five sample
      sets had been collected. Ventilator-associated pneumonia (VAP) pathogens were
      identified, quantified and genotyped. Microbial findings were highly correlated
      both between airway locations and over time when samples were taken no more than
      72 h apart. If no VAP pathogen was present in the oral flora, it was unlikely to
      be found in a lower airway sample; i.e., the positive predictive value of the
      oropharyngeal sample was 0.73 (95% CI 0.67-0.80), and the negative predictive
      value was 0.95 (95% CI 0.92-0.99). Colonisation with Enterobacteriacae, non
      fermentative bacteria and Staphylococcus aureus was monoclonal in the airways and
      over time, whereas colonisation with microbes normally found in the oropharynx,
      i.e., Haemophilus influenzae, Haemophilus parainfluenzae and Streptococcus
      pneumoniae, was polyclonal. When antibiotics were used, the chance of recovering
      VAP pathogens from all sampling sites was reduced three-fold. No correlation was
      observed between a bacterial count of > or =10(4) CFU/mL in BAL fluid and chest X
      rays compatible with VAP.

PMID- 17430339
TI  - Molecular epidemiology of a clonal outbreak of multidrug-resistant Acinetobacter
      baumannii in a university hospital in Italy.
AB  - This study investigated the molecular epidemiology of a clonal outbreak of
      multidrug-resistant Acinetobacter baumannii that occurred between June 2003 and
      June 2004 in a tertiary-care hospital in Naples, Italy. A. baumannii was isolated
      from 74 patients, of whom 38 were infected and 36 were colonised. Thirty-three
      patients had ventilator-associated pneumonia, three had hospital-acquired
      pneumonia, and two had sepsis. Genotypic analysis of 45 available A. baumannii
      isolates revealed two distinct pulsed-field gel electrophoresis (PFGE) patterns.
      Of these, PFGE pattern 1 was represented by isolates from 44 patients and was
      identical to that of an epidemic A. baumannii clone isolated in another hospital
      of Naples during 2002. All A. baumannii isolates of PFGE type 1 showed identical
      multiresistant antibiotypes, characterised by resistance to all antimicrobial
      agents tested, including carbapenems, with the exception of colistin. In these
      isolates, inhibition of OXA enzymes by 200 mM NaCl reduced the imipenem MIC by up
      to four-fold. Molecular analysis of antimicrobial resistance genes showed that
      all A. baumannii isolates of PFGE type 1 harboured a class 1 integron containing
      the aacA4, orfX and bla(OXA-20) gene cassettes, an ampC gene and a bla(OXA-51)
      like allele. Moreover, a bla(OXA-58)-like gene surrounded by the regulatory
      elements ISAba2 and ISAba3 was identified in a 30-kb plasmid from A. baumannii
      isolates of PFGE type 1, but not PFGE type 2. Thus, selection of a single A.
      baumannii clone producing an OXA-58-type carbapenem-hydrolysing oxacillinase was
      responsible for the increase in the number of A. baumannii infections that
      occurred in this hospital.

PMID- 17430341
TI  - New allergy intervention strategies: hitting the mucosal road.

PMID- 17430342
TI  - The asthma-obesity link in childhood: open questions, complex evidence, a few
      answers only.
AB  - Obesity and asthma are public health priorities in developed countries. Genes
      which may contribute to the control of both conditions include those encoding for
      the beta2-adrenergic receptor, tumour necrosis factor-alpha (TNF-alpha) and the
      insulin-like growth factor 1 (IGF-1). Prospective studies consistently supported
      a link between obesity and reported wheezing or asthma diagnosis in children.
      However, there are still no clear explanations for such a link. On one hand,
      overweight asthmatic children may perceive their asthma as worse. On the other
      hand, atopic sensitization and bronchial hyper-reactivity do not explain the
      observed associations. After puberty, the association between asthma and obesity
      tends to be stronger in girls than in boys. It is conceivable that severe obesity
      in adolescent females may aggravate asthma through mechanisms different from
      those linking prepubertal obesity to unremitting asthma in males. Future studies
      should therefore address multiple age- and gender-specific hypotheses about the
      mechanisms that link obesity to asthma throughout childhood.

PMID- 17430343
TI  - Further marches: allergic and non-allergic.

PMID- 17430344
TI  - Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis.
AB  - BACKGROUND: Sublingual immunotherapy (SLIT) is a clinically effective treatment
      in both pollen and house dust mite-induced rhinitis and asthma. However, the
      mechanisms by which this is accomplished are not clear. OBJECTIVE: The objective
      of the current study was to establish a mouse model of rhinitis in order to study
      the effect and mechanisms of SLIT. METHODS: Mice were sensitized by
      intraperitoneal injections of alum-adsorbed Phleum pratense extract. Sensitized
      mice were SLIT-treated and subsequently challenged intranasally and analysed for
      clinical symptoms, antibody levels, eosinophilia and T cell response. RESULTS:
      Intranasal challenge of sensitized mice led to the development of rhinitis
      characterized by significantly increased sneezing and influx of eosinophils into
      the nose. Levels of specific IgE were fivefold increased in nasopharyngeal lavage
      (NAL) fluid and more than doubled in serum. Furthermore, a T-helper type 2 (Th2)
      like T cell response was observed in local draining lymph nodes. SLIT treatment
      of sensitized mice reduced sneezing, eosinophilia and IgE levels in the NAL by
      more than 50%. Moreover, serum levels of IgE and IgG1 as well as T cell response
      in the draining lymph nodes were also significantly reduced. Treatment for a
      shorter time or with a lower dose only led to minor reductions of the clinical
      and immunological parameters, indicating that the effect of SLIT is time and dose
      dependent. CONCLUSION: In the present study, we have established a mouse model
      displaying the hallmarks of allergic rhinitis using a clinically relevant
      allergen. Using this model, we have demonstrated that SLIT treatment is able to
      reduce allergic symptoms in a time- and dose-dependent manner.

PMID- 17430345
TI  - Probiotic-induced suppression of allergic sensitization and airway inflammation
      is associated with an increase of T regulatory-dependent mechanisms in a murine
      model of asthma.
AB  - BACKGROUND: Microbial intestinal colonization in early in life is regarded to
      play a major role for the maturation of the immune system. Application of non
      pathogenic probiotic bacteria during early infancy might protect from allergic
      disorders but underlying mechanisms have not been analysed so far. OBJECTIVE: The
      aim of the current study was to investigate the immune effects of oral
      application of probiotic bacteria on allergen-induced sensitization and
      development of airway inflammation and airway hyper-reactivity, cardinal features
      of bronchial asthma. METHODS: Newborn Balb/c mice received orally 10(9) CFU every
      second day either Lactobacillus rhamnosus GG or Bifidobacterium lactis (Bb-12)
      starting from birth for consecutive 8 weeks, during systemic sensitization (six
      intraperitoneal injections, days 29-40) and airway challenge (days 54-56) with
      ovalbumin. RESULTS: The administration of either Bb-12 or LGG suppressed all
      aspects of the asthmatic phenotype: airway reactivity, antigen-specific
      immunoglobulin E production and pulmonary eosinophilia (mean: 137 vs. 17 and 13
      cellsx10(3)/mL, respectively). Antigen-specific recall proliferation by spleen
      cells and T-helper type 2 cytokine production (IL-4, IL-5 and IL-10) by
      mesenteric lymph node cells also showed significant reduction, while TGF
      production remained unchanged. Oral LGG administration particularly suppressed
      allergen-induced proliferative responses and was associated with an increase in
      numbers of TGF-beta-secreting CD4+/CD3+ T cells in mesenteric lymph nodes (6.5,
      16.7%) as well as nearly 2-fold up-regulation of Foxp3-expressing cells in
      peribronchial lymph nodes. CONCLUSIONS: Neonatal application of probiotic
      bacteria inhibits subsequent allergic sensitization and airway disease in a
      murine model of asthma by induction of T regulatory cells associated with
      increased TGF-beta production.

PMID- 17430346
TI  - Differences in the composition of intestinal Bifidobacterium species and the
      development of allergic diseases in infants in rural Japan.
AB  - BACKGROUND: Bifidobacterium is a dominant genus in the intestinal microbiota of
      infants and comprises many different species. A series of studies performed in
      northern Europe showed differences in the composition of Bifidobacterium species
      between allergic infants and healthy controls. Additional studies are needed to
      confirm this observation. OBJECTIVE: To investigate the composition of fecal
      Bifidobacterium species in allergic infants and healthy controls in Japan, using
      molecular methods. METHODS: Full-term born babies were followed up to 6 months of
      age at a local hospital in rural Japan. The presence or absence of allergy was
      determined based on allergic symptoms and skin prick tests. Fecal Bifidobacterium
      species in allergic infants (n=10), and healthy controls (n=16) were evaluated
      using nine Bifidobacterium species-specific or group-specific primers based on
      16S rDNA sequences at 1, 3, and 6 months of age. RESULTS: The number of the
      infants in whom no Bifidobacterium species could be found was four (15.4%) at 1
      month, two (7.7%) at 3 months, and one (3.3%) at 6 months of age, all of whom
      were healthy controls. At 1 month of age, allergic infants had a higher
      prevalence f the Bifidobacterium catenulatum group than healthy controls (60.0%
      vs. 6.3%, P<0.01). At 6 months of age, allergic infants had a higher prevalence
      of B. bifidum than healthy controls (70.0% vs. 12.5%, P<0.01). These differences
      were not related to feeding method. CONCLUSIONS: Our results in infants in rural
      Japan support the hypothesis that a compositional difference in intestinal
      Bifidobacterium species may be associated with the development of allergy in
      early infancy, although the responsible species might vary among countries or
      races.

PMID- 17430347
TI  - Vaccinations, infections and antibacterials in the first grass pollen season of
      life and risk of later hayfever.
AB  - BACKGROUND: It has been hypothesized that early-life exposure to vaccinations,
      infections or antibacterials influence allergic disease development. Concurrent
      exposure to grass pollens may alter any effect. OBJECTIVE: To test the hypothesis
      that exposure to antibacterials, vaccinations (DTP or MMR) or specific infections
      during the first grass pollen seasons of life influences the risk of hayfever
      more than at any other time of the year. METHODS: Nested case-control studies
      were based on birth cohorts within two large databases of computerized patient
      records from UK general practices: the General Practice Research Database (GPRD)
      and Doctors' Independent Network (DIN). Seven thousand ninety-eight hayfever
      cases, diagnosed after age 2, were matched to controls for practice, age, sex and
      follow-up of control to case ascertainment date. Conditional logistic regression
      was used to compare exposure by age 1 (age 2 for MMR) inside vs. outside the
      grass pollen season (May, June, July). Odds ratios (ORs) were pooled across
      databases. RESULTS: There were no associations in either database between MMR
      during vs. outside the grass pollen season and later hayfever. Of 23 infections
      studied, none were statistically significant; although analyses for the less
      common conditions were limited by low statistical power. The pooled OR for
      hayfever comparing exposure to antibacterials only in the grass pollen season
      with only outside it was 1.20 (95% CI 0.98-1.47) and for DTP was 0.84 (95% CI
      0.72-0.98). CONCLUSION: Although an interaction between early exposure to
      microbial agents and concurrent grass pollen exposure on hayfever risk seemed
      plausible, there was little evidence to support it across a range of analyses.
      However, the effect of DTP though weak deserves further study.

PMID- 17430348
TI  - Maternal fish intake during pregnancy and atopy and asthma in infancy.
AB  - BACKGROUND: There is growing evidence that n-3 fatty acids have anti-inflammatory
      properties and may modulate immune response. Dietary intake of these nutrients
      during pregnancy could play a role in the risk of asthma and atopy in the
      offspring. METHODS: Using data from a cohort of women (n=462) enrolled during
      pregnancy and whose offspring were followed up to 6 years, we evaluated the
      impact of fish consumption during pregnancy on the incidence of atopy and asthma.
      Dietary intake was assessed by food frequency questionnaire (42 items) applied by
      an interviewer. RESULTS: Thirty-four percent of infants had a medical diagnosis
      of eczema at age 1 year, 14.3% of the children were atopic [based on skin prick
      test (SPT) at 6 years], and 5.7% had atopic wheeze at age 6 years. After
      adjusting for potential confounding factors, fish intake during pregnancy was
      protective against the risk of eczema at age 1 year, a positive SPT for house
      dust mite at age 6 years and atopic wheeze at age 6 years [odds ratio (OR)=0.73
      95% confidence interval (CI) 0.55-0.98, OR=0.68, 95% CI 0.46-1.01 and OR=0.55,
      95% CI 0.31-0.96, respectively]. For an increase in fish intake from once per
      week to 2.5 times per week, the risk of eczema at age 1 year decreased by 37%,
      and the risk of positive SPT at age 6 years by 35%. Stratification by
      breastfeeding showed that fish intake was significantly related to a decrease
      risk in persistent wheeze among non-breastfed children (P for interaction<0.05).
      No protective effect was observed among breastfed children. CONCLUSION: Our data
      suggest a protective effect of fish intake during pregnancy on the risk of atopy
      related outcomes.

PMID- 17430349
TI  - Eczema, atopy and allergen exposure in adults: a population-based study.
AB  - BACKGROUND: There are few published studies on geographical variation in
      prevalence of eczema in adults or its association with recognised risk factors
      for allergic disease. OBJECTIVE: To describe the geographical variation in
      prevalence of eczema in adults, assess the associations with sociodemographic
      risk factors, serum-specific IgE and IgG, and exposure to allergen. METHODS: A
      community-based sample of 8206 adults aged 27-56 years, in 25 European centres
      and Portland, USA, provided questionnaire information on symptoms of eczema.
      Serum-specific IgE to house dust mite (HDM), cat, grass and Cladosporium, and IgG
      and IgG4 to HDM and cat were measured. Mattress levels of mite and cat allergen
      were assessed. RESULTS: Overall prevalence of eczema was 7.1% (range between
      countries of 2.2-17.6%). Eczema was associated with female gender [odds ratio
      (OR) 1.25; 95% confidence interval (CI) (1.01-1.55)], family history of atopic
      disease (OR 1.43; 95% CI 1.18-1.74), IgE sensitization to at least one allergen
      (OR 1.50; 95% CI 1.19-1.90), particularly Cladosporium (OR 3.65; 95% CI 1.81
      7.37), and total IgE. Eczema was negatively associated with age and no clear
      associations were observed with sibship size, mattress mite and cat allergen
      levels or with cat and HDM-specific IgG or IgG4. CONCLUSIONS: There is
      geographical variation in the prevalence of eczema in adults both within and
      between countries. Although the disease is associated with IgE sensitization, in
      this study it was not related to mattress mite or cat allergen levels.

PMID- 17430350
TI  - The temporal sequence of allergic sensitization and onset of infantile eczema.
AB  - BACKGROUND: Eczema is commonly associated with sensitization in infants, but the
      causative role of sensitization in the development of eczema has been questioned.
      OBJECTIVE: To determine if allergic sensitization increases the risk of
      developing eczema, or alternatively, if eczema increases the risk of developing
      allergic sensitization. METHODS: We used data from the Melbourne Atopy Cohort
      Study, a prospective birth cohort of 552 infants with a family history of atopic
      disease. The main outcomes were risk of developing eczema from 6 months to 7
      years of age in asymptomatic infants; and risk of developing sensitization, as
      measured by skin prick tests to milk, egg white, peanut, house dust mite, rye
      grass pollen and cat extracts, in previously unsensitized infants. RESULTS:
      Sensitization to food extracts at 6 months was associated with an increased risk
      of developing eczema [hazard ratio (HR) 1.63, 95% confidence interval 1.13-2.35]
      up to 7 years of age, after excluding infants with eczema in the first 6 months.
      However, eczema in the first 6 months was also associated with increased risk of
      new sensitization at both 1 year (HR 2.34, 1.38-3.98) and 2 years (HR 3.47, 1.65
      7.32). CONCLUSION: In some infants, sensitization precedes and predicts the
      development of eczema, while in others eczema precedes and predicts the
      development of sensitization. This indicates that there are multiple pathways to
      atopic eczema.

PMID- 17430351
TI  - Increasing prevalence of atopic eczema in Taiwanese adolescents from 1995 to
      2001.
AB  - BACKGROUND: The prevalence of atopic eczema in adolescents has recently been
      reported as increasing in many countries, a phenomenon yet to be fully explained.
      This study compared the prevalence of atopic eczema among Taiwanese adolescents
      with individual-level risk factors and community-level data of temperature,
      relative humidity, and air pollutants to determine whether changes in these
      factors could explain the observed change in prevalence. METHODS: We conducted
      two nationwide, cross-sectional surveys of atopic illness and symptoms among
      Taiwanese 12-15-year-old schoolchildren in 1995-1996 and 2001. The effects of
      personal and environmental factors were assessed and temporal changes of outdoor
      monitoring data were also compared with the prevalence difference of atopic
      eczema. RESULTS: A total of 42 919 adolescents from the 1995 to 1996 survey and
      10 215 adolescents from the 2001 survey attended schools located within 1 km of
      22 monitoring stations. The 12-month prevalence of atopic eczema increased
      significantly during this period [adjusted prevalence ratio (PR)=1.43, 95%
      confidence interval (CI) 1.21-1.70 in boys; PR=1.77, 95% CI 1.49-2.10 in girls].
      After adjustment for potential risk factors, the prevalence differences were
      statistically unchanged. Although parental education level contributed the most,
      changes in personal and environmental factors might not explain the observed
      prevalence increases of atopic eczema. Temporal change in the relative humidity
      was significantly associated with prevalence increase among boys but its
      contribution was also small. CONCLUSION: Correlates of the investigated risk
      factors that have changed over time still underlie the prevalence increases of
      atopic eczema in Taiwanese adolescents. The exact reasons for the rising trends
      remain to be elucidated.

PMID- 17430352
TI  - Near-fatal asthma phenotype in the ENFUMOSA Cohort.
AB  - BACKGROUND: Near-fatal asthma (NFA) is characterized by severe asthma attacks
      usually requiring intensive care unit admission. This phenotype of asthma has
      been studied mainly in acute conditions. METHODS: The aim of our study was to
      compare the clinical, functional and inflammatory characteristics of NFA patients
      with mild to severe asthmatics in stable conditions. We recruited 155 asthmatic
      patients from five centres of the European Network for Understanding Mechanisms
      of Severe Asthma: 67 patients with mild-to-moderate asthma controlled by
      low/medium doses of inhaled corticosteroids; 64 with severe asthma that, despite
      treatment with high doses of inhaled corticosteroids, long-acting beta2-agonists
      and for 1/3 also with regular oral corticosteroids, had at least one asthma
      exacerbation in the previous year; 24 with an NFA episode in the previous 5 years
      in the absence of inclusion criteria for the previous groups. All the patients
      were examined in stable conditions. RESULTS: NFA patients were taking less
      corticosteroids and were less compliant to prescribed asthma medications than the
      other two groups of patients. Lung function, blood gases, atopic status, sputum
      and blood inflammatory cell count of NFA patients were similar to mild-to
      moderate, but not severe, asthmatic patients. CONCLUSIONS: In stable conditions
      patients with an NFA attack in the previous 5 years cannot be distinguished from
      patients with mild-to-moderate asthma, while they are different from severe
      asthmatics both in terms of lung function and of airway inflammation. The risk
      factor that characterizes this group of patients is reduced usage of prophylactic
      corticosteroids.

PMID- 17430353
TI  - Decompensation of pollen-induced asthma in two towns with different pollution
      levels in La Mancha, Spain.
AB  - BACKGROUND: Allergic diseases have increased in industrialized countries and this
      increase is associated not only with genetic factors but also with lifestyle and
      environmental factors such as air pollution. Our hypothesis was that asthma in
      pollen-allergic patients from two towns with very different pollution levels in
      La Mancha (Spain) could be affected to a very different degree. OBJECTIVE: Our
      objectives were to assess the risk factors associated with decompensation of
      pollen-induced asthma in the two towns and to perform a comparison between the
      patients from Puertollano (high pollution level) and Ciudad Real (low pollution
      level) with respect to daily symptoms, medication used and peak-flow
      measurements. METHODS: We designed a cohort study with 137 patients (66 from
      Puertollano and 71 from Ciudad Real), conducted over 3 years (1999-2001) and
      including two pollen seasons. The two populations presented similar demographic
      and clinical characteristics. The variables studied included: area of residence,
      sex, age, smoking status, asthma symptoms and positive prick tests. Clinical
      decompensation was monitored by symptoms recorded on diary cards, twice daily
      peak-flow measurements and the use of protocolized medication. RESULTS: There was
      a clinically relevant relationship between the place of residence and clinical
      decompensation. The risk of clinical decompensation in patients from Puertollano
      was up to three times higher than that of patients in Ciudad Real (P=0.034).
      Furthermore, patients from Puertollano and patients with moderate asthma
      presented more rapid decompensation compared with patients from Ciudad Real
      (P=0.020) and patients with mild asthma (P=0.049). CONCLUSION: In conclusion,
      pollen-allergic asthmatics in Puertollano present a poorer clinical course and
      become decompensated earlier than those from Ciudad Real and it could be due to
      air pollution.

PMID- 17430355
TI  - CD4+CD25+ T cells regulate the intensity of hypersensitivity responses to peanut,
      but are not decisive in the induction of oral sensitization.
AB  - BACKGROUND: Naturally occurring CD4+CD25+ regulatory T cells (Tregs) play a
      critical role in the maintenance of self-tolerance and it has been suggested that
      these Tregs may also be involved in preventing allergic disease. OBJECTIVE: The
      precise role of CD4+CD25+ T cells in the regulation of allergic responses to
      mucosal antigens remains to be elucidated. In the present study, it was
      investigated whether CD4+CD25+ T cells are involved in the induction of oral
      tolerance and whether they play a role in controlling hypersensitivity responses
      to food proteins. METHODS: CD4+CD25+ T cells were depleted with PC61 mAb before
      the induction of low dose oral tolerance to peanut extract (PE). In addition,
      CD4+CD25+ T cell depletion was performed during sensitization or before oral
      challenge, using a C3H/HeOuJ mouse model of allergic sensitization to peanut.
      RESULTS: Oral tolerance to PE could not be induced in CD4+CD25+ T cell-depleted
      mice. However, CD4+CD25+ T cell depletion during long-term exposure to PE alone
      did not result in allergic sensitization. In sensitized mice, anti-CD25 treatment
      during oral exposure resulted in higher levels of PE-specific IgE and increased
      mast cell degranulation upon an oral challenge. In contrast, anti-CD25 treatment
      of PE-sensitized mice before oral challenges did not affect the level of mast
      cell degranulation. CONCLUSION: These results indicate that CD4+CD25+ Tregs are
      involved in maintaining tolerance to oral antigens and regulate the intensity of
      an IgE-mediated food hypersensitivity response, but are not crucial in preventing
      sensitization. Accordingly, CD4+CD25+ Tregs may represent a potential tool for
      the treatment of food allergic disorders.

PMID- 17430354
TI  - Comparison of allergenicity and immunogenicity of an intact allergen vaccine and
      commercially available allergoid products for birch pollen immunotherapy.
AB  - BACKGROUND: Specific immunotherapy with intact allergen vaccine is a well
      documented treatment for allergic diseases. Different vaccine formulations are
      currently commercially available, the active ingredient either being intact
      allergens or chemically modified allergoids. The rationale behind allergoids is
      to decrease allergenicity while maintaining immunogenicity. However, data from
      the German health authorities based on reporting of adverse events over a 10-year
      period did not indicate increased safety of allergoids over intact allergens.
      OBJECTIVE: The objective of this study was to investigate the effect of chemical
      modification on allergenicity and immunogenicity comparing four commercial
      allergoid products for birch pollen immunotherapy with an intact allergen
      vaccine. METHODS: Solid-phase IgE inhibition and histamine release assays were
      selected as model systems for allergenicity, and a combination of human T cell
      proliferation and IgG titres following mouse immunizations were used to address
      the immunogenicity of the intact allergen vaccine and the four allergoids. In all
      assays, the products were normalized with respect to the manufacturer's
      recommended maintenance dose. RESULTS: IgE inhibition experiments showed a change
      in epitope composition comparing intact allergen vaccine with allergoid. One
      allergoid product induced enhanced histamine release compared to the intact
      allergens, while the other three allergoids showed reduced release. Standard T
      cell stimulation assays using lines from allergic patients showed a reduced
      response for all allergoids compared with the intact allergen vaccine regardless
      of the cell type used for antigen presentation. All allergoids showed reduced
      capacity to induce allergen-specific IgG responses in mice. CONCLUSION: While
      some allergoids were associated with reduced allergenicity, a clear reduction in
      immunogenicity was observed for all allergoid products compared with the intact
      allergen vaccine, and the commercial allergoids tested therefore do not fulfil
      the allergoid concept.

PMID- 17430356
TI  - Influence of plant lipids on immune responses in mice to the major Brazil nut
      allergen Ber e 1.
AB  - BACKGROUND: Lipids, particularly bacterial lipopolysaccharide, can impact on
      immune responses to proteins, with low doses enhancing type 2 responses.
      OBJECTIVE: We have examined the influence of natural plant lipid extracts on
      antibody responses provoked in mice by recombinant Ber e 1, the major allergen in
      Brazil nuts. METHODS: BALB/c strain mice were immunized (by intraperitoneal
      injection) with natural or recombinant Ber e l produced in Pichia pastoris and
      admixed with various lipid fractions isolated from Brazil nuts. Serum samples
      were analysed for specific IgE antibody by homologous passive cutaneous
      anaphylaxis assay and for IgG by enzyme-linked immunosorbant assay. RESULTS:
      Exposure to recombinant (lipid-free) Ber e 1 alone failed to induce detectable
      IgG or IgE antibody. Co-administration of the total lipid fraction (with reduced
      triglyceride levels), sterol-rich, or polar lipid fractions, resulted in marked
      adjuvant effects on IgG and IgE. However, the beta-sitosterol and glycolipid-rich
      fractions were associated with only low-level IgG antibody, and had little impact
      on IgE antibody production. Natural Ber e 1 containing endogenous lipids also
      provoked IgG and IgE antibody responses. Identical IgE and IgG antibody responses
      were detected regardless of whether natural or recombinant Ber e 1 was used as
      substrates for analyses. CONCLUSION: Endogenous Brazil nut lipids are required
      for the induction of optimal antibody responses to Ber e 1 in the BALB/c strain
      mouse. Appropriate antibody binding sites are present on both natural and
      recombinant forms of Ber e 1, suggesting that the impact of lipid is at the
      induction phase, rather than antibody recognition, and is possibly required for
      efficient antigen presentation.

PMID- 17430357
TI  - Association and functional relevance of E237G, a polymorphism of the high
      affinity immunoglobulin E-receptor beta chain gene, to airway hyper
      responsiveness.
AB  - BACKGROUND: The hyper-sensitivity reaction of IgE, with its high-affinity
      receptors (FcepsilonRI), is central to the phenomenon of atopic diseases.
      OBJECTIVE: To evaluate the genetic effects of non-synonymous single-nucleotide
      polymorphisms (SNPs) of FcepsilonRI on intermediate phenotypes of asthma, i.e.
      atopy and airway hyper-responsiveness (AHR), in the Korean general population.
      SUBJECTS AND METHODS: Atopy and AHR were evaluated in a cohort of 2055 subjects,
      aged 10-18 years, using skin prick tests (SPTs) for common aeroallergens and
      total serum IgE and methacholine bronchial provocation tests. All FcepsilonRI
      alpha, FcepsilonRI-beta, and FcepsilonRI-gamma gene exons of 24 healthy subjects
      were sequenced to locate informative non-synonymous SNPs (minor allele
      frequency>2%). Informative SNPs were then scored, using the high-throughput
      single base extension method. Relative risk (RR) was determined by multiple
      logistic regression analysis, after adjusting for confounding factors. The
      functional relevance of non-synonymous SNPs was analysed using the sorting
      intolerant from tolerant (SIFT) program. RESULTS: The SNP search found only one
      informative non-synonymous SNP in FcepsilonRI-beta: E237G (minor allele
      frequency=0.21). The positive rate of AHR was lower among subjects with the 237*E
      allele than among those with 237*G [RR (95% confidence interval)=0.41 (0.19
      0.89); P=0.01]. However, the E237G substitution was not associated with either a
      positive SPT response or total serum IgE levels. Sequence evolution analysis
      predicted that the E237G variation is an intolerant amino acid substitution, with
      functional importance. CONCLUSION: In the Korean general population, AHR is
      significantly associated with the E237G polymorphism of FcepsilonRI-beta, which
      results in an intolerant amino acid substitution.

PMID- 17430358
TI  - Effects of Rho-kinase inactivation on eosinophilia and hyper-reactivity in murine
      airways by allergen challenges.
AB  - BACKGROUND: A small GTPase, Rho, and its target molecule, Rho-kinase, play an
      important role in the cell functions, including contractility, chemotaxis,
      adhesion, and migration. It is generally considered that eosinophilic
      inflammation and hyper-reactivity to methacholine in airways are fundamental to
      the pathophysiology of bronchial asthma. OBJECTIVE: This study was designed to
      determine whether the Rho/Rho-kinase pathways are involved in the eosinophil
      recruitment and airway hyper-reactivity. We investigated inhibitory effects of
      fasudil, a specific inhibitor of Rho-kinase, on acute allergic inflammation in
      mice. METHODS: BALB/c mice were sensitized and challenged with ovalbumin (OVA).
      OVA-challenged mice were treated orally with fasudil (3, 10, 30 mg/kg) or saline
      before each OVA challenge. Total cell counts, differential cell counts,
      cytokines, and chemokines levels were measured in bronchoalveolar lavage (BAL),
      and lungs were examined histologically. Moreover, respiratory resistance in
      response to methacholine was measured. RESULTS: When fasudil was administrated to
      OVA-challenged mice, increased cell numbers of total cells and eosinophils were
      significantly attenuated in a dose-dependent manner. However, inflammatory cells
      other than eosinophils were not affected by fasudil. Fasudil caused a dose
      dependent inhibition in increased levels of IL-5, IL-13, and eotaxin in BAL fluid
      by OVA challenges. Histological analysis of the airways revealed that both
      infiltration of inflammatory cells and goblet cell hyperplasia were significantly
      suppressed in fasudil treatment. Furthermore, fasudil significantly suppressed
      the augmented responsiveness to methacholine induced by OVA challenges.
      CONCLUSION: Oral administration of fasudil inhibits eosinophil recruitment,
      goblet cell hyperplasia and airway hyper-reactivity by allergen challenges. These
      effects of this agent may be mediated by suppressing a chemokine and cytokines
      related to the pathophysiology of bronchial asthma such as eotaxin, IL-5, and IL
      13. Our findings provide evidence that inhibition of the Rho/Rho-kinase pathway
      may be beneficial for bronchial asthma.

PMID- 17430359
TI  - Cysteinyl leukotrienes enhance tumour necrosis factor-alpha-induced matrix
      metalloproteinase-9 in human monocytes/macrophages.
AB  - BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an important enzyme responsible
      for airway remodelling. Monocytes/macrophages have a cysteinyl leukotriene 1
      (cysLT1) receptor, but its function is poorly understood. OBJECTIVE: To elucidate
      the function of the cysLT1 receptor of human monocytes/macrophages in MMP-9
      production. METHODS: We examined the effect of cysLTs (LTC4, -D4 and -E4) on TNF
      alpha-induced MMP-9 production in THP-1 cells, a human monocytic leukaemia cell
      line and peripheral blood CD14+ monocytes/macrophages. In addition, we examined
      the effect of pranlukast, a cysLT1 receptor antagonist, on the enhancement of TNF
      alpha-induced MMP-9 production by cysLTs. RESULTS: ELISA revealed that LTC4 and 
      D4, but not -E4, enhanced TNF-alpha-induced MMP-9 production in THP-1 cells and
      peripheral blood CD14+ monocytes/macrophages. Real-time polymerase chain reaction
      demonstrated that LTC4 and -D4, but not -E4, increased MMP-9 mRNA expression
      induced by TNF-alpha in THP-1 cells. Moreover, we demonstrated that pranlukast
      completely inhibited the enhancement of TNF-alpha-induced MMP-9 production by
      LTC4 and -D4 in THP-1 cells and peripheral blood CD14+ monocytes/macrophages.
      CONCLUSION: LTC4 and -D4 enhanced the TNF-alpha-induced MMP-9 production via
      binding the cysLT1 receptor in human monocytes/macrophages. Pranlukast inhibited
      the enhancements by LTC4 and D4.

PMID- 17430360
TI  - Percutaneous application of peptidoglycan from Staphylococcus aureus induces
      eosinophil infiltration in mouse skin.
AB  - BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with
      immunopathologic features that vary depending on the duration of the lesion. The
      lesioned skin of AD patients shows an increased number of inflammatory cells such
      as eosinophils, mast cells and mononuclear cells in the dermis and superficial
      Staphylococcus aureus colonization. OBJECTIVE: The purpose of this study was to
      determine the effects of peptidoglycan (PEG) from S. aureus on eosinophil
      induction in murine skin. METHODS: PEG was applied to the barrier-disrupted
      abdominal skin of mice every 5 days. Twenty days later, the number of eosinophils
      in the abdominal skin was counted. The cytokine response in the skin was
      investigated by RT-PCR and immunohistological analysis. The regulated-upon
      activation in normal T cells expressed and secreted (RANTES) production from
      cultured epidermal cells was measured by ELISA. RESULTS: The skin of mice treated
      with PEG showed a significantly increased number of eosinophils compared with
      that of mice treated with vehicle alone. In addition, application of PEG to the
      abdominal skin of mice increased the expression of mRNA for RANTES, but not that
      of mRNA for eotaxin, eotaxin-2 and monocyte chemotactic protein-3 in the skin.
      Immunohistologic analysis demonstrated that the levels of RANTES transcripts
      corresponded with those of protein synthesis in the epidermis. In vitro
      experiments using epidermal Langerhans cells (LCs) and keratinocytes (KCs) showed
      that RANTES production was induced by LCs but not by KCs stimulated with PEG.
      Furthermore, an intraperitoneal injection of anti-RANTES antibody neutralized the
      induction of eosinophils in the skin. CONCLUSION: These results suggest that PEG
      may have an ability to induce eosinophil infiltration in the skin through RANTES
      production by LCs, and would explain the role of S. aureus colonization in AD
      patients.

PMID- 17430361
TI  - An fMRI study of working memory for schematic facial expressions.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine neuronal
      activation in relation to increasing working memory load in an n-back task, using
      schematic drawings of facial expressions and scrambled drawings of the same
      facial features as stimuli. The main objective was to investigate whether working
      memory for drawings of facial features would yield specific activations compared
      to memory for scrambled drawings based on the same visual features as those
      making up the face drawings. fMRI-BOLD responses were acquired with a 1.5 T
      Siemens MR scanner while subjects watched the facial drawings alternated with the
      scrambled drawings, in a block-design. Subjects had to hold either 1 or 2 items
      in working memory. We found that the main effect of increasing memory load from
      one to two items yielded significant activations in a bilaterally distributed
      cortical network consisting of regions in the occipitotemporal cortex, the
      inferior parietal lobule, the dorsolateral prefrontal cortex, supplementary motor
      area and the cerebellum. In addition, we found a memory load x drawings
      interaction in the right inferior frontal gyrus in favor of the facial drawings.
      These findings show that working memory is specific for facial features which
      interact with a general cognitive load component to produce significant
      activations in prefrontal regions of the brain.

PMID- 17430362
TI  - Effect of skill level on recall of visually presented patterns of musical notes.
AB  - Expertise effects in music were studied in a new task: the construction of mental
      representations from separate fragments. Groups of expert musicians and non
      musicians were asked to recall note patterns presented visually note by note.
      Skill-level, musical well-formedness of the note patterns and presentation mode
      were varied. The musicians recalled note patterns better than the non-musicians,
      even though the presentation was visual and successive. Furthermore, only
      musicians' performance was affected by musical well-formedness of the note
      patterns when visual gestalt properties, verbal rehearsability, and familiarity
      of the stimuli were controlled. Musicians were also able to use letter names
      referring to notes as efficiently as visual notes, which indicates that the
      better recall of musicians cannot be explained by perceptual visual chunking.
      These results and the effect of skill level on the distribution of recall errors
      indicate that the ability to chunk incoming information into meaningful units
      does not require that complete familiar patterns are accessible to encoding
      processes, yet previous knowledge stored in long-term memory affects
      representation construction in working memory. The present method offers a new
      reliable tool, and its implications to the research on construction of
      representations and musical imagery are discussed.

PMID- 17430363
TI  - Saccade landing point selection and the competition account of pro- and
      antisaccade generation: the involvement of visual attention--a review.
AB  - This paper presents a review and summary of experimental findings on the role of
      attention in the preparation of saccadic eye movements. The focus is on
      experiments where performance of prosaccades (saccades towards a suddenly
      appearing item) and antisaccades (saccades of equal amplitude in the direction
      opposite to where the target moved) is compared. Evidence suggests that these two
      opposite responses to the same stimulus event entail competition between neural
      pathways that generate reflexive movements to the target and neural mechanisms
      involved in inhibiting the reflex and generating a voluntary gaze shift in the
      opposite direction to the target appearance. Evidence for such a competition
      account is discussed in light of a large amount of experimental findings and the
      overall picture clearly indicates that this competition account has great
      explanatory power when data on saccadic reaction times and error rates are
      compared for the two types of saccade. The role of attention is also discussed in
      particular in light of the finding that the withdrawal of attention by a
      secondary task 200 to 500 ms before the saccade target appears, leads to speeded
      antisaccades (without a similar increase in error rates), showing that the
      results do not simply reflect a speed-accuracy trade-off. This result indicates
      that the tendency for "reflexive" prosaccades is diminished when attention is
      engaged in a different task. Furthermore, experiments are discussed that show
      that as the tendency for a reflexive prosaccade is weakened, antisaccades are
      speeded up, further supporting the competition account of pro- and antisaccade
      generation. In the light of evidence from neurophysiology of monkeys and humans,
      a tentative model of pro- and antisaccade generation is proposed.

PMID- 17430364
TI  - The importance of impaired physical health and age in normal cognitive aging.
AB  - The objective of this study was to investigate the importance of impaired
      physical health and age in normal cognitive aging. In our cross-sectional,
      clinical and explorative study, medical and neuropsychological data from 118
      voluntary healthy controls aged 26-91 years were collected from five recruitment
      occasions. Health was assessed according to a criterion reflecting clinical and
      subclinical severity. The examinations included a clinical investigation, brain
      neuroimaging, and a comprehensive neuropsychological assessment. Regression
      analyses showed a significant incidence of clinical and subclinical medical
      disorders that explained 10.8% of the variation in cognitive performance, while
      age-related impairment explained 5.6%. Findings of the central nervous system
      were important but various other medical findings explained about half of the
      health-related variation. Cognitively demanding tasks were more susceptible to
      impaired physical health while tasks comprising salient motor- and visual spatial
      elements were more prone to be impaired by age. Our findings suggest (1) that
      impaired physical health is more important than chronological age in accounting
      for cognitive impairment across the adult lifespan, (2) that age and health
      dissociate with regard to cognitive functions affected, and (3) that selection
      for so-called "super healthy" elderly people might be justified in cognitive
      research. Because the prevalent diseases in normal aging are potentially
      preventable, the present findings promise good prospect for prevention of future
      cognitive disability among elderly people.

PMID- 17430365
TI  - Psychometric properties of the Obsessive Compulsive Inventory-Revised among
      Icelandic college students.
AB  - In the present study, the psychometric properties of the Obsessive Compulsive
      Inventory-Revised (OCI-R) (Foa, et al., 2002) were investigated. The OCI-R was
      administered to a total of 816 Icelandic college students. The Maudsley Obsessive
      Compulsive Inventory (MOCI) and the Penn State Worry Questionnaire (PSWQ) were
      administered to a subsample of 304 students, and the PI-WSUR (Padua Inventory
      Washington State University Revision), the PSWQ and the Multidimensional
      Perfectionism Scale (MPS) to another subsample of 212 students. Also, 89 students
      filled in the OCI-R twice with two weeks in between. The factor structure of the
      instrument was replicated in a confirmatory factor analysis. Cronbach's alpha and
      test-retest reliabilities of the OCI-R total scale and all subscales were
      satisfactory. Further, the OCI-R total score showed a significantly higher
      correlation with the PI-WSUR and the MOCI than with the PSWQ or the MPS. Finally,
      conceptually similar scales of the OCI-R and the MOCI as well as the PI-WSUR
      showed higher inter-correlations than the correlations that were observed between
      conceptually more distinct scales. It is concluded that the Icelandic version of
      the OCI-R has strong psychometric properties in a student population.

PMID- 17430366
TI  - Type A behavior and work situation: associations with burnout and work
      engagement.
AB  - The aim of the present study was to investigate Type A behavior as well as
      perceived work situation, and associations with burnout and work engagement. The
      associations in focus were investigated through hierarchical regressions in a
      sample (N= 329) of Swedish Information Communication Technology consultants. The
      findings indicated that both work situation and Type A behavior was correlated
      with work engagement and burnout; however, no interactions between Type A
      behavior and work situation were elicited. The main conclusion was that the
      achievement striving aspect of Type A behavior appears as "non-toxic" and is
      related only to work engagement. However, the irritability/impatience aspect
      appears to be responsible for burnout complaints among Type A individuals,
      possibly through negative effects of the mood itself than through perceived
      stress at work.

PMID- 17430367
TI  - Stability and change in work values among male and female nurses and engineers.
AB  - Gender related changes of work values were analyzed in a longitudinal
      questionnaire study of 173 male and 48 female engineers and 353 female and 31
      male nurses at three measurement occasions covering about four and half years
      from the end of their vocational education. At all occasions, Social relations
      were rated as more important by women than by men and Altruism was given higher
      ratings by the nurses than by the engineers. Within both occupations women's mean
      Altruism ratings were higher than men's mean ratings, and in all groups except
      male engineers the mean ratings dropped between the three occasions. Women's
      ratings of Benefits and career and Influence were strengthened in both
      occupations, thereby eliminating an initial gender difference. The stability of
      work values is discussed in terms of challenges and norms in working life.

PMID- 17430368
TI  - Factors associated with a positive attitude towards change among employees during
      the early phase of a downsizing process.
AB  - Most research on organizational changes in working life, including downsizing,
      focuses on the negative attitudes and negative consequences of the change. The
      aim of this study was to evaluate if the employee's previous learning experience
      and characteristics of the working environment were associated with positive
      attitudes towards organizational change. The 467 employees (73.5% males) working
      in a global oil company in the early phases of a downsizing process were asked to
      answer a questionnaire with demographic variables, perception of the working
      environment, and attitude to change (93% response rate). Corporate social
      responsibility (CSR), involvement and participation, team leadership and team
      effectiveness were important factors related to positive attitudes towards
      organizational change. Non-leaders and older employees were positive to change.
      We conclude that employees' perceptions of their psychosocial working
      environment, in particular the CSR, were highly related to their attitude to
      organizational change.

PMID- 17430369
TI  - Bullying at work: a discussion of definitions and prevalence, based on an
      empirical study.
AB  - The past 15 years have witnessed a growing interest in studies of bullying in the
      area of work and organizational psychology, but the results of research on this
      topic seem to indicate very wide variations in the prevalence of bullying. The
      range of differences may be primarily due to the utilization of different
      categories and operationalizations of the concept. The aim of this study is to
      discuss definitions and delimitations of the phenomenon known as bullying, and to
      demonstrate empirically how the prevalence of bullying can be determined by the
      way in which it is defined and delimited. On the background of a discussion of
      some current definitions of bullying and a survey of some central research
      results on its rate of occurrence, this study presents the results of a study of
      3,024 public-sector employees. The results showed that 1.0% of the sample
      reported that they had been bullied weekly during the previous six months, while
      4.7% reported themselves as having been exposed to acts of bullying with the same
      frequency and for the same period of time. If we change the criteria from
      "weekly" to "2-3 times a month" the prevalences rise to 3.7% and 26.9%. Based on
      observations of bullying the prevalence is 3.3%. The results are discussed with
      reference to other studies that are comparable in terms of delimitations and
      rates of occurrence and it is concluded that the prevalence is at the same level
      as these.

PMID- 17430370
TI  - Impulsivity as a predictor of newly diagnosed depression.
AB  - Depression is a severe mental disorder, whose onset has been related to
      environmental, genetic and personality factors. This study examined the
      association between impulsivity and incidence of depression. Logistic regression
      models were related to prospective data from two surveys (2-year time lag)
      conducted in a large cohort of hospital employees (N= 4,505). Only respondents
      with no history of depression at baseline were included. Impulsivity was
      predictive of the onset of depression (OR = 1.95, CI 95%= 1.28-2.97) after
      adjustment for age, sex and education. This association remained statistically
      significant after additional adjustment for a variety of baseline
      characteristics, such as smoking, alcohol consumption, and size of social
      network. A measure of mental distress (GHQ-12 responses), which may serve as a
      proxy measure for undiagnosed depression, was also associated with impulsivity.
      Impulsivity appears to be a distinct personality factor that may contribute to
      the onset of depressive illness in adults.

PMID- 17430371
TI  - Regaining a sense of agency and shared self-reliance: the experience of advanced
      disease cancer patients participating in a multidimensional exercise intervention
      while undergoing chemotherapy--analysis of patient diaries.
AB  - Evidence is emerging that exercise can reduce psychological distress in cancer
      patients undergoing treatment. The present study aimed to (qualitatively) explore
      the experiences of advanced disease cancer patients participating in a 6-week, 9
      hours weekly, structured, group-based multidimensional exercise intervention
      while undergoing chemotherapy. Unstructured diaries from a purposive sample of
      three females and two males (28-52 years old) who participated in the program
      served as the database. Data were analyzed using a phenomenological, narrative
      method. The analysis yielded three themes: shifting position, self-surveillance,
      and negotiated strength. The intervention highlighted situations making it
      possible for the participants to negate psychological and physical constraints.
      The concept of structured exercise contains viable psychotherapeutic potentials
      by allowing the development of alternative bodily and mental realities complying
      with cancer patients' demands and abilities to regain autonomy and commitment to
      discover and adopt a sense of agency and shared self-reliance.

PMID- 17430372
TI  - Mohs surgery for the treatment of melanoma in situ: a review.
AB  - BACKGROUND: Controversy exists in the literature regarding the use of Mohs
      surgery for the treatment of melanoma in situ (MIS). Mohs surgery provides the
      advantage of complete margin assessment; however, variations in surgical and
      laboratory techniques employed, make comparison of outcomes difficult. OBJECTIVE:
      To review the current literature regarding Mohs surgery for treatment of MIS and
      to evaluate treatment options. METHODS: We review the literature regarding
      traditional excision margins for MIS, the proportion of biopsy-proven MIS lesions
      that prove to have an invasive component, and the efficacy of Mohs surgery for
      MIS. RESULTS: Many authors report a need for surgical margins larger than the
      recommended 5 mm, particularly with MIS arising in sun-exposed areas. Further, a
      review of the literature reveals that nearly one-quarter of biopsy-proven MIS
      lesions are found to contain invasive melanoma after complete surgical removal
      and pathologic examination. Substantial evidence supports the value of complete
      margin assessment in the treatment of MIS, particularly in the head and neck
      region. CONCLUSION: Complete surgical excision with careful margin assessment is
      required to adequately treat MIS lesions, particularly given the high rate of
      invasive melanoma in lesions initially thought to be MIS. Mohs surgery remains
      the treatment of choice for all clinically ill-defined MIS.

PMID- 17430373
TI  - Perioperative management of von Willebrand disease in dermatologic surgery.
AB  - BACKGROUND: Von Willebrand disease (VWD) is the most common inherited bleeding
      disorder, affecting an estimated 0.1% to 1% of the population. It is caused by a
      qualitative or quantitative defect of von Willebrand factor. Primary
      manifestations include intractable mucocutaneous bleeding after surgery or
      trauma. OBJECTIVE: The objective was to review the pathophysiology and clinical
      features of VWD and to propose a perioperative management strategy for patients
      with this condition undergoing dermatologic surgery. METHODS AND MATERIALS:
      Literature is reviewed. RESULTS: The various types and clinical manifestations of
      this condition are reviewed, and a perioperative strategy is presented for
      managing patients with VWD who undergo cutaneous oncologic or cosmetic surgical
      procedures. CONCLUSIONS: In most cases, dermatologic surgery can be safely
      performed in patients with VWD. The use of appropriate therapeutic prophylaxis in
      conjunction with a hematologist is indicated in high-risk, nonelective
      procedures.

PMID- 17430374
TI  - High-risk cutaneous squamous cell carcinoma without palpable lymphadenopathy: is
      there a therapeutic role for elective neck dissection?
AB  - PURPOSE: The beneficial role of elective neck dissection (END) in the management
      of high-risk cutaneous squamous cell carcinoma (CSCC) of the head and neck
      remains unproven. Some surgical specialists suggest that END may be beneficial
      for patients with clinically node-negative (N0) high-risk CSCC, but there are few
      data to support this claim. We reviewed the available literature regarding the
      use of END in the management of both CSCC and head and neck SCC (HNSCC).
      METHODOLOGY: The available medical literature pertaining to END in both CSCC and
      HNSCC was reviewed using PubMed and Ovid Medline searches. RESULTS: Many surgical
      specialists recommend that END be routinely performed in patients with N0 HNSCC
      when the risk of occult metastases is estimated to exceed 20%; however, patients
      who undergo END have no proven survival benefit over those who are initially
      staged as N0 and undergo therapeutic neck dissection (TND) after the development
      of apparent regional disease. There is a lack of data regarding the proper
      management of regional nodal basins in patients with N0 CSCC. In the absence of
      evidence-based data, the cutaneous surgeon must rely on clinical judgment to
      guide the management of patients with N0 high-risk CSCC of the head and neck.
      CONCLUSIONS: Appropriate work-up for occult nodal disease may occasionally be
      warranted in patients with high-risk CSCC. END may play a role in only a very
      limited number of patients with high-risk CSCC.

PMID- 17430375
TI  - Correlation of thickness of basal cell carcinoma by optical coherence tomography
      in vivo and routine histologic findings: a pilot study.
AB  - BACKGROUND: Optical coherence tomography uses advanced photonics and fiber optics
      to obtain high-resolution cross-sectional images and tissue characterization in
      real time. OBJECTIVE: The objective was to correlate measurements of the depth of
      basal cell carcinomas obtained by optical coherence tomography and standard
      histopathologic examinations. METHODS: Twenty previously scanned optical
      coherence tomography images of histopathologically confirmed basal cell carcinoma
      were reviewed. A computer-generated depth scale was used to measure the depth of
      the neoplasm. These measurements were compared with direct measurements of tumor
      thickness of analogous tissue specimens made with a microscope micrometer.
      RESULTS: All 20 sites demonstrated excellent correlation of tissue thickness, to
      a depth of about 1 mm, estimated by optical coherence tomography or routine
      histopathologic tests. This depth correlation was consistent across several
      different types of basal cell carcinoma observed. CONCLUSION: Optical coherence
      tomography, compared with routine histopathologic techniques, shows promise as a
      method for estimating the superficial thickness of basal cell carcinoma.

PMID- 17430376
TI  - Treatment of Bowen's disease with topical 5% imiquimod cream: retrospective
      study.
AB  - BACKGROUND: Topical 5% imiquimod cream is an FDA-approved treatment for
      superficial basal cell carcinomas. It has also been utilized in the treatment of
      Bowen's disease (squamous cell in situ). The current literature on this subject,
      however, is scant, and this treatment is only validated by case reports and two
      small open label studies. OBJECTIVE: The objective was to assess the efficacy of
      topical 5% imiquimod cream in the treatment of squamous cell in situ in a larger
      open-label case series. METHODS A retrospective study of 49 patients was
      performed. RESULTS: Forty-two of the 49 (86%) patients in the study had a
      complete response with topical imiquimod. The remaining 7 (14%) failed therapy
      and required additional treatments. The mean follow-up duration was 19 months,
      with a range of 1 to 44 months. CONCLUSION: Topical 5% imiquimod cream appears to
      be clinically beneficial in the treatment of Bowen's disease and should be
      considered as a treatment option.

PMID- 17430377
TI  - 5% 5-Fluorouracil cream for the treatment of small superficial Basal cell
      carcinoma: efficacy, tolerability, cosmetic outcome, and patient satisfaction.
AB  - BACKGROUND: Five percent 5-fluorouracil (5-FU) cream is approved by the FDA for
      the treatment of superficial basal cell carcinomas but has been underutilized.
      OBJECTIVE: The objective was to evaluate the efficacy, tolerability, cosmetic
      outcome, and patient satisfaction of 5% 5-FU in the treatment of superficial
      basal cell carcinomas. MATERIALS AND METHODS: A total of 29 patients with 31
      biopsy-proven superficial basal cell carcinoma lesions on the trunk or limbs were
      treated with 5% 5-FU cream twice daily for up to 12 weeks. Treatment could be
      stopped sooner if the lesion was clinically resolved. The lesional site was
      surgically excised 3 weeks after the end of treatment for histologic evaluation
      of cure. RESULTS The histologic cure rate was 90% (28/31 lesions cured) and the
      mean time to clinical cure was 10.5 weeks. 5-FU was generally well tolerated with
      a good cosmetic outcome-the majority of patients had no pain or scarring and only
      mild erythema. Patients were generally very satisfied with their treatment.
      CONCLUSION: Five percent 5-FU is a highly effective and well-tolerated treatment
      option for superficial basal cell carcinomas offering a generally good cosmetic
      outcome and high levels of patient satisfaction.

PMID- 17430378
TI  - A split-face comparison study of pulsed 532-nm KTP laser and 595-nm pulsed dye
      laser in the treatment of facial telangiectasias and diffuse telangiectatic
      facial erythema.
AB  - BACKGROUND AND OBJECTIVES: Pulsed 595 nm and 532 nm lasers can effectively
      diminish or eliminate facial telangiectasia. We performed a split-face, single
      blind, controlled, comparison study in an effort to determine their individual
      and comparative efficacy. STUDY DESIGN/MATERIALS AND METHODS: Fifteen patients
      were treated using a 595-nm PDL on one side of the face and a pulsed 532-nm
      potassium-titanyl-phosphate (KTP) laser on the other. Each subject was evaluated
      at 3 weeks after three treatments. RESULTS: Both devices improved telangiectasia.
      The 532-nm device, however, was at least as effective or more effective than the
      595-nm laser in all subjects. On average, the KTP laser achieved 62% clearing
      after the first treatment and 85% clearing 3 weeks after the third treatment,
      compared to 49% and 75% for the PDL, respectively. Seventy-nine percent of KTP
      laser-treated patients continued to have swelling for greater than 1 day versus
      71% of PDL-treated patients. Of those patients who noted persistent erythema for
      at least 1 day after treatment, 58% noted more erythema on the KTP laser-treated
      side compared to 8% on the PDL-treated side. CONCLUSIONS: Both the 595-nm and the
      532-nm pulsed lasers are highly effective in the treatment of facial
      telangiectasia and redness. The 532-nm KTP laser appears to be more effective but
      causes more swelling and erythema.

PMID- 17430379
TI  - Objective evaluation of the effect of intense pulsed light on rosacea and solar
      lentigines by spectrophotometric analysis of skin color.
AB  - BACKGROUND: To date, intense pulsed light (IPL) has been applied to various skin
      diseases, but there have been few objective evaluations of its efficacy.
      OBJECTIVE: The aim of this study was to perform objective evaluations of the
      effect of the IPL system on rosacea and solar lentigines. METHODS: Twelve
      patients with rosacea were treated with IPL at the wavelength of 550 to 670 nm,
      three times every 4 weeks, and the skin color was determined with L(*)a(*)b(*)
      color space using a spectrophotometer. In addition, 18 patients with solar
      lentigines were treated once, and the lightness L(*) was determined. RESULTS In
      all of 6 erythematotelangiectatic rosacea patients and in 5 of 6 papulopustular
      rosacea patients, each of the L(*)a(*)b(*) values of the posttreated lesions
      approached those of normal skin areas (efficacy rate, 91.6%). The mean level of
      the L(*)a(*)b(*) values improved significantly after treatment and particularly
      in the erythematotelangiectatic rosacea patients. In 12 of 18 patients with solar
      lentigines, the lightness L(*) was elevated after treatment (efficacy rate,
      66.6%). CONCLUSION: As demonstrated by spectrophotometric analysis of skin color,
      IPL at the wavelength of 550 to 670 nm is effective for rosacea and solar
      lentigines, particularly most useful for erythematotelangiectatic rosacea.

PMID- 17430380
TI  - Analysis of 602 Chinese cases of nevus of Ota and the treatment results treated
      by Q-switched alexandrite laser.
AB  - BACKGROUND: Nevus of Ota is a congenital or acquired pigmentary disorder of the
      skin and mucous membranes, which are areas innervated by the first and second
      branches of the trigeminal nerve. Nevus of Ota is very common in Asia. Nevus of
      Ota was effectively treated with Q-switched alexandrite (755 nm) laser, but no
      detailed report existed on many Chinese cases treated with Q-switched alexandrite
      laser. OBJECTIVE: The objective was to gauge clinical and treatment data and
      material statistics for 602 cases of nevus of Ota and analyze its pathogenic
      mechanism and therapeutic results. METHODS: A total of 602 cases of clinical data
      on nevus of Ota were collected by means of clinical registration, photo
      verification, and telephone inquiry or correspondence. CONCLUSIONS: There are
      some differences in sex, age, and local regions in nevus of Ota. Nevus of Ota can
      combine with other diseases. The treatment of Nevus of Ota by a Q-switched
      alexandrite laser is safe and effective. Additional treatment will achieve good
      results. The results correlate to the eyelids and Tanino's classification.

PMID- 17430381
TI  - A pilot study on the effect of epinephrine on botulinum toxin treatment for
      periorbital rhytides.
AB  - BACKGROUND: Relaxation of hyperactive facial muscles by injection of botulinum
      toxin type A (BOTOX, Allergan Inc., Irvine, CA) represents the most common
      cosmetic procedure performed in the United States. OBJECTIVE: The objective of
      this split-face randomized double-blind study was to determine the effect of
      epinephrine (EPI) on the efficacy of BOTOX treatment of muscle hyperactivity in
      the upper face. MATERIALS AND METHODS: Fourteen subjects (ages 39-57 years) with
      moderate to severe periorbital rhytides were enrolled. Study patients were
      blinded to the two treatment arms, BOTOX and BOTOX plus EPI 1:100,000. Subjective
      and objective evaluations were performed at 0 and 4 days and 1, 3, and 6 months,
      and clinical improvement was assessed using a nominal scale from 0 to 4,
      corresponding to 0, 1% to 25%, 26% to 50%, 51% to 75%, and 76% to 100%
      improvement, respectively. The incidence of adverse events was also recorded.
      RESULTS Fourteen subjects with moderate to severe periorbital rhytides were
      treated with BOTOX or BOTOX plus EPI. One subject was discontinued from the study
      after receiving asymmetric doses of BOTOX. At 4, 30, and 90 days after treatment,
      subjective and objective improvement scores revealed that EPI enhanced the
      efficacy of BOTOX when compared to BOTOX alone. By 3 months, the effect of BOTOX
      and BOTOX plus EPI had peaked and continued to fall through 6 months. One of 14
      patients did not appear to respond to BOTOX treatment. Both treatments were well
      tolerated with no serious adverse events. CONCLUSION: To our knowledge, we are
      the first to test under randomized double-blind conditions the effect of EPI on
      efficacy of BOTOX. Our data suggest that addition of EPI may accelerate the rate
      of onset as well as the short-term efficacy of BOTOX for treatment of periorbital
      rhytides.

PMID- 17430382
TI  - Catheter-assisted vein sclerotherapy: a new approach for sclerotherapy of the
      greater saphenous vein with a double-lumen balloon catheter.
AB  - OBJECTIVE: We sought to optimize sclerotherapy of the greater saphenous vein
      (GSV) by targeted application of foamed sclerosant by using a catheter. METHODS:
      We designed a new double-lumen catheter that is inserted into the GSV. Via one
      lumen, a balloon at the tip of the catheter can be inflated to stop the blood
      flow. Via the second lumen, the sclerosing agent can be injected and aspirated.
      This method enabled us to perform a targeted application of the sclerosing agent
      [catheter-assisted vein sclerotherapy (KAVS)]. In an open study, outpatients
      suffering from varicosis of the GSV received a foam sclerotherapy under
      ultrasound guidance, using the newly developed KAVS catheter. RESULTS: Thirty
      patients with an insufficiency (reflux) of the GSV were treated with the newly
      developed KAVS method using foamed polidocanol. The intervention was well
      tolerated in all patients without the occurrence of serious side effects. In 27
      of the 30 treated patients (90%), we found a closure of the GSV at control visits
      6 weeks, 3 months, and 6 months after treatment. CONCLUSIONS: The KAVS method
      represents a feasible approach for sclerotherapy of the GSV. The efficiency and
      treatment modalities need to be explored in further studies.

PMID- 17430383
TI  - Nasolabial hinge flap with simultaneous cartilage graft in nasal alar and tip
      reconstruction.

PMID- 17430384
TI  - W-modification of Abbe flap after Mohs surgery of squamous cell carcinoma on the
      lower lip.

PMID- 17430385
TI  - Triple synchronous cutaneous melanoma: a clinical, dermoscopic, and genetic case
      study.

PMID- 17430386
TI  - Infection of polypropylene threads for face-lifting with Mycobacterium fortuitum.

PMID- 17430387
TI  - Bowen's disease on porokeratotic eccrine ostial and dermal duct nevus.

PMID- 17430388
TI  - Solitary fibrous tumor attached to the cervical vertebra.

PMID- 17430389
TI  - Pilonidal cyst of the scalp due to single minor trauma.

PMID- 17430390
TI  - Subungual angiomyxolipoma.

PMID- 17430391
TI  - Verrucous carcinoma presenting as giant plantar horns.

PMID- 17430392
TI  - Radiotherapy for rodent ulcer type of basal cell carcinoma.

PMID- 17430393
TI  - Anchored rotation flap for infraorbital cheek reconstruction: a case series.

PMID- 17430394
TI  - Art of the lip.

PMID- 17430396
TI  - Short waitlist time does not adversely impact outcome following liver
      transplantation for hepatocellular carcinoma.
AB  - It has been suggested that patients with hepatocellular carcinoma (HCC)
      undergoing living donor liver transplantation (LDLT) have worse recurrence-free
      survival compared to deceased donor liver transplantation (CLT), leading to the
      hypothesis that short waitlist time or fast-tracking may include more aggressive
      tumors that would have been selected out by traditionally longer waitlist time.
      The primary aim of the present study was to evaluate the impact of waitlist time
      on HCC recurrence. The study cohort included 100 patients meeting T2 criteria by
      imaging before undergoing CLT (n = 90) or LDLT (n = 10). The 5-year recurrence
      free probability was 89.9% for the entire cohort, and 91.9%, 90.5% and 86.6%,
      respectively, for waitlist time of 3 months or less, 3-6 months and > 6 months (p
      = 0.81). In the Cox proportional hazards model, waitlist time was also not a
      significant predictor of HCC recurrence. Tumor under-staging was observed in
      20.5% of patients with waitlist time 3 months or less and 23.0% for waitlist time
      > 3 months (p = 0.81). In conclusion, our results failed to show an association
      between waitlist time and outcome after CLT or LDLT for HCC, and provided
      evidence disputing a significant role of waitlist time in the selection against
      HCC with unfavorable tumor biology.

PMID- 17430397
TI  - Brain death activates donor organs and is associated with a worse I/R injury
      after liver transplantation.
AB  - The majority of transplants are derived from donors who suffered from brain
      injury. There is evidence that brain death causes inflammatory changes in the
      donor. To define the impact of brain death, we evaluated the gene expression of
      cytokines in human brain dead and ideal living donors and compared these data to
      organ function following transplantation. Hepatic tissues from brain dead (n =
      32) and living donors (n = 26) were collected at the time of donor laparotomy.
      Additional biopsies were performed before organ preservation, at the time of
      transplantation and one hour after reperfusion. Cytokines were assessed by real
      time reverse transcriptase-polymerase chain reaction (RT-PCR) and cytometric bead
      array. Additionally, immunohistological analysis of tissue specimens was
      performed. Inflammatory cytokines including IL-6, IL-10, TNF-alpha, TGF-beta and
      MIP-1alpha were significantly higher in brain dead donors immediately after
      laparotomy compared to living donors. Cellular infiltrates significantly
      increased in parallel to the soluble cytokines IL-6 and IL-10. Enhanced immune
      activation in brain dead donors was reflected by a deteriorated I/R injury proven
      by elevated alanin-amino-transferase (ALT), aspartat-amino-transferase (AST) and
      bilirubin levels, increased rates of acute rejection and primary nonfunction.
      Based on our clinical data, we demonstrate that brain death and the events that
      precede it are associated with a significant upregulation of inflammatory
      cytokines and lead to a worse ischemia/reperfusion injury after transplantation.

PMID- 17430398
TI  - Abdominal wall transplantation with microsurgical technique.
AB  - Many patients undergoing intestinal or multivisceral transplantation have a past
      history of complete midgut removal with the loss of the domain of the abdominal
      compartment or have severely damaged abdominal walls from repeated laparotomies,
      tumours or enterocutaneous fistulae. These patients may encounter severe
      abdominal wall closure problems at the end of transplantation, resulting in
      increased morbidity and mortality. It is, therefore, of paramount importance to
      properly cover transplanted organs in order to reduce postoperative
      complications. Abdominal wall transplantation was recently proposed for closure
      of patients undergoing both small-bowel and multivisceral transplantation: the
      results are encouraging. However, the technical procedure proposed requires the
      procurement of long segments of iliac vessels as far as the vena cava and the
      aorta. Since donor multiorgan procurement involves many surgical teams, the
      removal of these vessels, with the abdominal graft, led to their unavailability
      for vascular surgeons. Here we present three consecutive cases of abdominal wall
      transplantation in which, by taking advantage of microsurgical experience, we
      were able to carry out a transplantation of the abdominal wall by direct
      anastomosis of the epigastric vessels, obtaining a very good outcome.

PMID- 17430399
TI  - High expression of Tim-3 mRNA in urinary cells from kidney transplant recipients
      with acute rejection.
AB  - TIM-3 is a recently described molecule specifically expressed on Th1
      differentiated T cells. We explored the usefulness of urinary mRNA profiles in
      the diagnosis of renal acute rejection (AR). Sixty urinary samples from renal
      transplant recipients simultaneously collected to allograft biopsy, (AR = 30 and
      No-AR =30), and 12 urinary samples from stable renal transplants were analyzed.
      Urinary mRNA encoding for TIM-3 and IFN-gamma were quantified using real time RT
      PCR. TIM-3 mRNA was highly expressed in AR (559.19 +/- 644.41) compared to No-AR
      (3.78 +/- 7.20), and stable transplants (0.54 +/- 0.76), p < 0.001. To a lesser
      degree, IFN-gamma mRNA transcripts were also increased in AR (50.40 +/- 38.71),
      compared with No-AR (4.69 +/- 12.62), and stable transplants (0.38 +/- 0.44) p <
      0.001. The highest expression of TIM-3 in AR makes it a promising noninvasive
      test for its diagnosis.

PMID- 17430400
TI  - Insurability of living organ donors: a systematic review.
AB  - Being an organ donor may affect one's ability to obtain life, disability and
      health insurance. We conducted a systematic review to determine if insurability
      is affected by living organ donation, and if concern about insurability affects
      donor decision making. We searched MEDLINE, EMBASE, SCI, EconLit and Cochrane
      databases for articles in any language, and reviewed reference lists from 1966
      until June 2006. All studies discussing the insurability of living organ donors
      or its impact on donor decision making were included. Data were independently
      abstracted by two authors, and the methodological quality appraised. Twenty-three
      studies, from 1972 to 2006, provided data on 2067 living organ donors, 385
      potential donors and 239 responses from insurance companies. Almost all companies
      would provide life and health insurance to living organ donors, usually with no
      higher premiums. However, concern about insurability was still expressed by 2%
      14% of living organ donors in follow-up studies, and 3%-11% of donors actually
      encountered difficulties with their insurance. In one study, donors whose
      insurance premiums increased were less likely to reaffirm their decision to
      donate. Based on available evidence, some living organ donors had difficulties
      with insurance despite companies reporting otherwise. If better understood, this
      potential barrier to donation could be corrected through fair health and
      underwriting policies.

PMID- 17430401
TI  - Effect of population aging on the international organ donation rates and the
      effectiveness of the donation process.
AB  - This study analyzed the effect of population aging on organ donation for
      transplants in 43 countries and on the effectiveness of the donation process by
      comparing the results between Spain and the United States. The percentage of the
      population aged 65 or over accounted for 33% of the difference in the donation
      rates between the countries and for 91% of the variation in the rates after age
      adjustment. However, the level of aging of the Spanish (16.5%) and American
      (12.3%) populations failed to account for the percentages of deceased donors 65
      or over (28% vs. 10%), due to the different age-specific donation rates, much
      higher in Spain above 50 years. These differences lead to a higher effectiveness
      of the process in the United States (3.1 transplanted organs per donor vs. 2.5 in
      Spain), though at lower rates of transplant per million population (73 vs. 87).
      We conclude that older populations have a greater donation potential as donation
      rates are strongly associated with population aging. It should therefore be
      mandatory to adjust donation rates for age before making comparisons.
      Additionally, effectiveness decreases with older donors, so age should be
      considered when establishing standards relating to organ donation and
      effectiveness of the process.

PMID- 17430402
TI  - Risk factors for urinary complications after renal transplantation.
AB  - Urinary complications are common following renal transplantation. The aim of this
      study is to evaluate the risk factors associated with renal transplant urinary
      complications. We collected data on 1698 consecutive renal transplants patients.
      The association of donor, transplant and recipient characteristics with urinary
      complications was assessed by univariable and multivariable Cox proportional
      hazards models, fitted to analyze time-to-event outcomes of urinary complications
      and graft failure. Urinary complications were observed in 105 (6.2%) recipients,
      with a 2.8% ureteral stricture rate, a 1.7% rate of leak and stricture, and a
      1.6% rate of urine leaks. Seventy percent of these complications were
      definitively managed with a percutaneous intervention. Independent risk factors
      for a urinary complication included: male recipient, African American recipient,
      and the "U"-stitch technique. Ureteral stricture was an independent risk factor
      for graft loss, while urinary leak was not. Laparoscopic donor technique
      (compared to open living donor nephrectomy) was not associated with more urinary
      complications. Our data suggest that several patient characteristics are
      associated with an increased risk of a urinary complication. The U-stitch
      technique should not be used for the ureteral anastomosis.

PMID- 17430403
TI  - General practitioners' reasons for the failure of a randomized controlled trial
      (The TIGER Trial) to implement epilepsy guidelines in primary care.
AB  - PURPOSE: To explore reasons for the failure of a randomized controlled trial to
      influence implementation of epilepsy guidelines in primary care, and to generate
      theory about likely contexts in which guidelines would lead to changes in
      clinician behavior. METHODS: Qualitative study based on focus groups and a single
      in-depth interview. Participants included 47 primary health care staff selected
      from a purposive sample of 13 urban and rural general practices. RESULTS: The key
      reason for the lack of implementation of the Scottish Intercollegiate Guidelines
      Network epilepsy guideline was an established pattern of general practitioner
      behavior, supported by practice staff, with which there was little perceived need
      to change. Secondary to this was a lack of knowledge of the existence and/or
      content of the guideline and perceived difficulties in implementing them in
      practice stemming from resource constraints and possible patient resistance. The
      individual behavior of clinicians was therefore rooted in wider service
      structures and policies. CONCLUSIONS: Guidelines may be more likely to be
      implemented where there are perceived problems with current service delivery.
      Attempts to facilitate the implementation of guidelines could also focus on areas
      where there is already a perceived need for guidance or a disruption in one of
      the underlying variables that maintain the health professional's role and
      practice. They may also be more likely where initiatives are focused more widely
      than individual physician behavior and are more broadly directed toward
      redesigning the wider care delivery systems by incorporating other providers to
      provide care coordination, enhancing patient self-management, and using
      information technology tools.

PMID- 17430405
TI  - Neocortical gliosis in temporal lobe epilepsy: gender-based differences.
AB  - OBJECTIVE: Sex hormones can influence the timing and frequency of seizure
      activity. In addition, gender may influence the age of epilepsy onset and
      hemispheric location of focal epilepsy. Whether gender alters temporal lobe
      pathologies differentially is not clear. In this study, we assess if neocortical
      or hippocampal pathologies from patients who underwent en bloc anteriomedial
      temporal lobectomy (AMTR) for medically refractory epilepsy differ by gender.
      METHOD: Consecutive en bloc AMTR resections (n = 128), including hippocampal
      tissues, were systematically studied. Cortical and intracortical gliosis from a
      standardized location, 1.5 cm from the temporal lobe tip, was assessed for
      quantifiable gliotic change. Corresponding hippocampal sections were
      characterized according to Watson grade. These outcomes were then compared by
      gender. Other correlates such as age of epilepsy onset, age of risk exposure, and
      duration of epilepsy were similarly compared. RESULTS: Subpial and intracortical
      gliosis was more pronounced in women (p = 0.02, p < 0.01). Cortical thickness was
      reduced in women compared to men (p < 0.05). No similar gender effects were seen
      in Watson grade of hippocampal sclerosis or CA1-4 neuronal dropout. CONCLUSIONS:
      Gender may differentially influence neocortical pathologies in patients with
      refractory temporal lobe epilepsy. No gender effect was seen when studying
      hippocampal pathologies.

PMID- 17430404
TI  - Reorganization of verbal and nonverbal memory in temporal lobe epilepsy due to
      unilateral hippocampal sclerosis.
AB  - PURPOSE: Patients with temporal lobe epilepsy (TLE) due to hippocampal sclerosis
      (HS) often suffer from material-specific memory impairments. The purpose of this
      study was to use functional magnetic resonance imaging (fMRI) to study the
      organization of specific memory functions in these patients. METHODS: We report
      14 patients with unilateral TLE and HS, and 10 controls, performing an fMRI
      memory paradigm of word, picture, and face encoding. RESULTS: Compared with
      controls, patients with left TLE demonstrated less left MTL and greater right MTL
      activation and patients with right TLE demonstrated less right MTL and greater
      left MTL activation. Correlations between fMRI activation and memory performance
      revealed greater activation in the damaged left hippocampus to be correlated with
      better verbal memory performance in left TLE patients and greater right
      hippocampal activation to be correlated with better nonverbal memory in right TLE
      patients. Conversely, greater fMRI activation in the contralateral hippocampus
      correlated with worse memory performance. CONCLUSIONS: Our findings suggest that
      memory function in unilateral TLE is better when it is sustained by activation
      within the damaged hippocampus and that reorganization to the undamaged MTL is an
      inefficient process, incapable of preserving memory function.

PMID- 17430406
TI  - Social functioning and psychological well-being of 347 young adults with epilepsy
      only--population-based, controlled study from Finland.
AB  - PURPOSE: To explore social functioning and psychological well-being in a
      population-based cohort of epilepsy patients compared to matched controls.
      METHODS: A random sample of patients with epilepsy (N = 347) and a healthy
      control group (N = 430) matched for age, gender and domicile were identified
      through National Registry of Social Insurance Institution in Finland. The data
      were collected by postal questionnaire assessing various factors related to
      social and psychological well-being and were analyzed by using linear regression
      analysis to compare the study and control groups. RESULTS: The age at onset of
      epilepsy was significantly associated with the level of further education and the
      level of seizure control with the employment status. The patients with epilepsy
      and lower level of basic education had also significantly lower level of further
      education, employment, and fewer social relations. Some differences in
      psychological well-being were also seen in those with matriculation examination
      when compared to matched controls. CONCLUSIONS: In young adults with well
      controlled epilepsy and successful basic education, social functioning is
      comparable with healthy peers. The importance of all social and educational
      support during the time of basic education may be crucial to favorable
      intellectual, functional, and social development later in life. Both professional
      and informal support is needed in adjunct to conventional treament of epilepsy,
      which is emphasized.

PMID- 17430407
TI  - Epilepsy and language development: the continuous spike-waves during slow sleep
      syndrome.
AB  - BACKGROUND: Continuous spike-waves during slow sleep syndrome (CSWSS) is a rare
      epileptic syndrome occurring in children, which is characterized by the
      association of epilepsy, neuropsychological disorders, and abnormal paroxysmal
      electroencephalographic (EEG) discharges activated by sleep. Language can be
      affected but, to date, language disorders and their long-term outcome have been
      documented only rarely. PURPOSES: Description of language impairment in patients
      with the CSWSS. METHODS: We performed a detailed language testing in 10 right
      handed children and adolescents with the CSWSS. Their pragmatic performance was
      compared to that of a control population of 36 children aged 6-10 years. RESULTS:
      Patients with CSWSS had lower scores in tests measuring their lexical,
      morphosyntactic, and pragmatic skills compared to controls. Comprehension remains
      unaffected. In addition, language impairment was found to be just as severe in
      patients in remission as those still in an active phase. CONCLUSIONS: We found
      severe language impairments in lexical and syntactic skills. The language profile
      is different from that observed in the Landau-Kleffner syndrome. Moreover
      patients in remission and those in an active phase of the CSWSS have the same
      language impairment profiles. This confirms the poor long-term neuropsychological
      prognosis. Our results raise points about the relationship between epileptic
      activity and language development. This pilot study underscores the need to
      assess language, and especially pragmatic skills, and to study long-term outcome
      in such childhood epileptic syndromes.

PMID- 17430408
TI  - Efficacy and tolerability of levetiracetam in children younger than 4 years: a
      retrospective review.
AB  - PURPOSE: To review our experience of the efficacy and tolerability of
      levetiracetam (LEV) in children younger than 4 years. METHODS: We used
      retrospective chart review to identify 122 children with seizures who were
      younger than 4 years and followed for >or=6 months. Efficacy was evaluated on the
      basis of the occurrence and durability of seizure remission. Tolerability was
      based on parent- and patient-reported side effects. RESULTS: Seventy (57%)
      subjects achieved seizure remission, and 52 (43%) did not. In univariate
      analysis, those achieving seizure remission were more likely to have partial
      epilepsy, require lower maintenance doses of LEV, and have fewer than two
      seizures per month at initiation of the medication. Only seizure frequency at
      initiation of LEV remained significant in multivariate analysis. The median
      duration of seizure freedom (8.9 month) was not influenced by age, epilepsy type,
      gender, or pretreatment seizure frequency. The dose of LEV was the only
      significant predictor of the duration of seizure remission, with longer duration
      of seizure remission seen in those taking <30 mg/kg/day compared with those
      taking > 30 mg/kg/day (median, 12.8 months vs. 3 months; p<0.0001). Side effects
      of LEV occurred in 34% of subjects but required discontinuation in only 16%, most
      commonly because of behavioral disturbances. CONCLUSIONS: LEV is an effective
      medication in children younger than 4 years and at doses lower than previously
      reported. It also well tolerated, suggesting that it represents an important
      option for the treatment of epilepsy in this age group.

PMID- 17430409
TI  - Anticonvulsive effect of a selective mGluR8 agonist (S)-3,4
      dicarboxyphenylglycine (S-3,4-DCPG) in the mouse pilocarpine model of status
      epilepticus.
AB  - PURPOSE: We sought to investigate the anticonvulsive and neuroprotective effect
      of a selective metabotropic glutamate receptor 8 (mGluR8) agonist (S)-3,4
      dicarboxyphenylglycines (S-3,4-DCPG) on pilocarpine-induced status epilepticus
      (PISE) and subsequent loss of hilar neurons in the dentate gyrus after systemic
      (intravenous) or local (intracerebroventricular) administration. We compared the
      difference in granular cell responses after paired-pulse stimulation of the
      perforant pathway and the sensitivity to local injection of S-3,4-DCPG into the
      stratum granulosum in the control and mice at 2 months after PISE. METHODS: We
      used intravenous, intracerebroventricular, or intrahippocampal administration of
      S-3,4-DCPG to mice with status epilepticus or temporal lobe epilepsy and
      neurophysiologic recording of somatic field excitatory postsynaptic potential
      (sfEPSP) and population spike (PS) of granular cells in response to perforant
      pathway stimulation or S-3,4-DCPG treatment. RESULTS: Intracerebroventricular
      (1.91 micromol) but not systemic administration of S-3,4-DCPG (at doses of 12.5,
      50, 100, 200, 400, 800, and 1,200 mg/kg) could control PISE with no
      neuroprotective effect. In epileptic mice, mGluR8-mediated inhibition of fEPSPs
      was reduced significantly in granular cell bodies. CONCLUSIONS: At doses ranging
      from 12.5 to 1,200 mg/kg, intravenous administration of S-3,4-DCPG may not be
      effective in controlling status epilepticus. Down-regulation of mGluR8 may be
      related to reduced S-3,4-DCPG-mediated inhibition and the subsequent occurrence
      of spontaneously recurrent seizures.

PMID- 17430410
TI  - Under-recruitment of patients for clinical trials: an illustrative example of a
      failed study.

PMID- 17430411
TI  - Is there a relationship between depression and crying? A review.
AB  - OBJECTIVE: To conduct a systematic examination of the relationship between
      depression and crying by reviewing all relevant theory and empirical data
      including the performance of crying items in measures of depression. METHOD:
      Review of the extant literature on depression and crying using PubMed, PsychInfo
      and Google Scholar databases. RESULTS: Scores on crying items of depression
      inventories correlate moderately with overall depression severity. Otherwise,
      there is surprisingly little evidence for the widespread claim that depression
      leads to more frequent and/or easier crying. There is also little empirical
      support for the competing claim that severely depressed individuals lose their
      capacity to cry. CONCLUSION: Current claims about the relationship between
      depression and crying lack a robust empirical foundation. Assessment instruments
      and diagnostic systems for mood disorders are inconsistent in how they handle
      crying as a symptom. Further work to investigate the causes and the context of
      crying in depressed patients is needed.

PMID- 17430412
TI  - Treating depression with the evidence-based psychotherapies: a critique of the
      evidence.
AB  - OBJECTIVE: While Cognitive Behaviour Therapy (CBT) and Interpersonal Therapy
      (IPT) have been positioned as first-line evidence-based treatments for
      depression, we suggest that limitations to the 'evidence' deserve wider
      appreciation. METHOD: A systematic literature search was undertaken, and
      limitations to the evidence base discussed. RESULTS: The review suggests that the
      specificity of CBT and IPT treatments for depression has yet to be demonstrated
      and details likely reasons. CONCLUSION: The superiority of CBT and IPT may well
      be able to be demonstrated across defined rather than universal circumstances. To
      achieve this aim, outcome research should move away from testing treatments as if
      they have universal application for heterogeneous disorder categories. Findings
      have distinct implications for the clinical management of depressive disorders,
      and particularly in relation to the utility of psychotherapy.

PMID- 17430413
TI  - Tranylcypromine vs. lamotrigine in the treatment of refractory bipolar
      depression: a failed but clinically useful study.
AB  - OBJECTIVE: To compare the efficacy and tolerability of tranylcypromine vs.
      lamotrigine in bipolar depression not responding to conventional antidepressants.
      METHOD: Bipolar depressed patients received open randomized treatment with
      tranylcypromine or lamotrigine as add-on to a mood stabilizer during 10 weeks. In
      a second treatment phase, non-responding patients could receive the opposite
      drug. Outcome criteria were response (measured with CGI-BP and IDS-C), switch
      into mania, and completion of the study. RESULTS: Only 20 of 70 planned patients
      were randomized, due to problems with recruitment, and 19 patients received any
      medication. During the first treatment phase 5/8 patients (62.5%) responded to
      tranylcypromine without switch into mania, compared with 4/11 patients (36.4%) on
      lamotrigine with two switches (statistically not significant). Over both
      treatment phases, 8/10 patients (80%) receiving tranylcypromine completed the
      study vs. 5/13 (38.5%) on lamotrigine (likelihood 0.02). CONCLUSION: There still
      appears to be a role for tranylcypromine in the treatment of refractory bipolar
      depression. Larger controlled studies are demanded.

PMID- 17430414
TI  - The validity and utility of patients' daily ratings of mood and impairment in
      clinical trials of bipolar disorder.
AB  - OBJECTIVE: Traditional cross-sectional clinician-rated measures have limited use
      in clinical trials of bipolar disorder. We examine the validity and usefulness of
      patients' daily ratings of mood and functional impairment during a treatment
      trial. METHOD: Ten subjects with bipolar II disorder completed daily ratings of
      depression severity, depression, hypomania and functional impairment over a 9
      month trial. Ratings were correlated with clinician-rated measures at nine time
      points to determine validity. Mood ratings were contrasted with cross-sectional
      data for one subject to determine usefulness of such fine-grained data. RESULTS:
      Moderate to large correlations were found between patients' and clinicians'
      ratings of mood and impairment for most of the nine time points. The utility of
      the patients' ratings relative to clinician-rated cross-sectional measures was
      also illustrated. CONCLUSION: Results support the validity and usefulness of
      patients' daily mood ratings.

PMID- 17430415
TI  - Generalized anxiety disorder: a 40-year follow-up study.
AB  - OBJECTIVE: There is insufficient knowledge of the long-term course of generalized
      anxiety disorder (GAD). We studied the course of this disorder in patients who
      were followed up for 40 years. METHOD: Patients admitted with the diagnosis of
      anxiety states ('anxious thymopathy' ) to the Lopez Ibor Neuropsychiatric
      Research Institute between 1950 and 1961 were examined between 1984 and 1988 (n =
      65). The retrospective diagnosis of GAD was made according to DSM-III-R criteria
      during 1984-1988 (first examination). A re-examination was performed by the same
      psychiatrist in the period 1997-2001 (n = 59; second examination). RESULTS: At
      first and second examinations 20% and 17% of subjects were diagnosed as GAD.
      Improvement was observed in 83%. GAD tended to disappear around age 50, but was
      replaced by somatization disorders. Lack of regular treatment compliance, female
      sex, and onset of GAD before age 25 were variables associated with a worse
      outcome. Undifferentiated somatization disorder was the most prevalent clinical
      status at follow-up. CONCLUSION: After several decades, participants improve with
      regard to GAD, although most continue to present somatizations.

PMID- 17430416
TI  - Neurocognitive indices of executive hypercontrol in obsessive-compulsive
      disorder.
AB  - OBJECTIVE: Cognitive impairment, more often involving memory and/or executive
      functions, has been reported in obsessive-compulsive (OC) patients. The present
      study aimed at: i) replicating, in an independent sample, previous findings by
      our group showing neurocognitive slowness limited to executive tasks; ii)
      assessing the influence of deficit in general cognitive abilities on executive
      dysfunction. METHOD: A comprehensive neuropsychological battery was administered
      to 30 drug-free OC patients and 30 healthy controls. RESULTS: Obsessive
      compulsive patients performed worse on visuospatial tests, were slower on
      executive tasks, and performed worse on the Wisconsin Card Sorting Test. After
      covarying for Wechsler Adult Intelligence Scale-Revised performance Intellectual
      Quotient, a lesser degree of executive dysfunction was observed. CONCLUSION:
      Obsessive-compulsive patients exhibit an impairment of executive functions,
      especially when tasks also require visuospatial abilities. The impairment might
      reflect a hyperactivity of the executive control.

PMID- 17430417
TI  - Reduced midbrain-pons serotonin transporter binding in patients with obsessive
      compulsive disorder.
AB  - OBJECTIVE: To evaluate current hypothesis regarding the pathophysiology of
      obsessive-compulsive disorder (OCD) by studying the serotonin receptor binding in
      patients with OCD using single photon emission computerized tomography (SPECT).
      METHOD: We studied nine patients (four men and five women, age range 21-56 years)
      fulfilling the DMS-III-R criteria for OCD using SPECT and the serotonin
      transporter (SERT) tracer (123)I-beta-CIT. SERT binding potential (BP2) was
      determined by Logan plot derived from seven scans obtained during 10-400 min.
      RESULTS: The binding of (123)I-beta-CIT in midbrain-pons was reduced in OCD
      patients when compared with controls (BP2 0.97 +/- 0.07 vs. 0.84 +/- 0.12, P =
      0.011). There was no correlation between BP2 and any of the clinical variables
      (age at onset, disease duration, and Yale-Brown Obsessive-Compulsive Scale
      score). CONCLUSION: This study suggests a reduced serotonergic input into the
      fronto-subcortical circuits in OCD, thereby diminishing the inhibitory regulation
      of serotonin on these circuits.

PMID- 17430419
TI  - What happens to children with PDD when they grow up? Prospective follow-up of 219
      children from preschool age to mid-childhood.
AB  - OBJECTIVE: To describe the psychological development of children with pervasive
      developmental disorders over a period of 3 years and to identify the factors
      linked to their developmental paths. METHOD: The study was a collaborative and
      prospective follow-up study of 219 preschoolers. Retrospective data and
      enrollment data were collected at the beginning of the study and 3 years later.
      RESULTS: We observed high variability in the short-term outcomes of preschoolers.
      In line with previous research, our results showed that intellectual, linguistic
      and adaptive functioning were useful for predicting outcome. The severity of a
      child's autistic symptoms appears to be related to his or her future development.
      These variables can therefore be used as predictors of outcome for preschoolers
      with autism. CONCLUSION: Developmental and symptom changes in young children with
      autism should not be overlooked and need to be assessed regularly in view of
      choosing suitable servicing programs.

PMID- 17430418
TI  - Temperament and response to the Trier Social Stress Test.
AB  - OBJECTIVE: The personality characteristics behavioural inhibition and neuroticism
      have been associated with mood and anxiety disorders and, in some studies,
      hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We recently reported
      that low levels of Novelty Seeking were associated with elevated plasma cortisol
      responses to the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test in
      healthy adults with no psychiatric disorder. The present study tested the
      association between temperament and HPA axis function in the same group of
      subjects using a standardized psychosocial neuroendocrine stress test. METHOD:
      Subjects completed diagnostic interviews, questionnaires, and the Trier Social
      Stress Test (TSST). RESULTS: Novelty Seeking was inversely associated with plasma
      cortisol concentrations at baseline and throughout the TSST, but was not related
      to adrenocorticotropic hormone (ACTH) levels. CONCLUSION: Results of this study
      extend our previous finding in the Dex/CRH test to a psychosocial stress test.
      Future investigations are needed to replicate these findings and further
      elucidate how temperament and personality are linked to HPA function.

PMID- 17430421
TI  - Is good school performance a risk factor for suicide in psychoses?

PMID- 17430422
TI  - Relationship between age and semen parameters in men with normal sperm
      concentration: analysis of 6022 semen samples.
AB  - This study evaluates retrospectively the relationship between age and semen
      parameters among men with normal sperm concentration. It was based on
      computerized data and performed in an Academic Fertility and IVF Unit. Six
      thousand and twenty-two semen samples with sperm concentrations of >or=20 x 10(6)
      ml(-1) were examined according to WHO criteria and analysed in relation to
      patients' age. For each age group, mean values +/- SD of semen volume, sperm
      concentration, percentage of motile spermatozoa, normal morphology, acrosome
      index, total sperm count/ejaculate, total motile sperm count/ejaculate and sexual
      abstinence duration were examined. A peak semen volume of 3.51 +/- 1.76 ml(-1)
      was observed at age >or=30 to <35 years and a lowest volume of 2.21 +/- 1.23 ml(
      1) was observed at age >or=55 years (P<0.05). Sperm motility was found to be
      inversely related to age with peak motility of 44.39 +/- 20.69% at age <25 years
      and lowest motility of 24.76 +/- 18.27% at age >or=55 years (P<0.05). A reduction
      of 54% was observed for total motile sperm, between values of 103.34 +/- 107 x
      10(6) at age >or=30 to <35 years and 46.68 +/- 53.73 x 10(6) (P<0.05) at age >55
      years. A statistically significant and inverse relationship was observed between
      semen volume, sperm quality and patient age, in spite of prolonged sexual
      abstinence duration. Top sperm parameters were observed at age >or=30 to <35
      years, while the most significant reduction in sperm parameters occurred after
      the age of 55 years.

PMID- 17430423
TI  - Bacille Calmette-Guerin intravesical instillation and erectile function: is there
      a concern?
AB  - The aim of our study was to evaluate the effect of bacille Calmette-Guerin (BCG)
      therapy on erectile function in a cohort of male patients affected by non-muscle
      invasive bladder cancer. Thirty male patients undergoing BCG treatment for non
      muscle invasive bladder cancer were enrolled in the study. Their mean age was
      60.4 years. None of the patients had risk factors for erectile dysfunction (ED).
      All subjects underwent a BCG standard schedule therapy (once weekly instillation
      for 6 weeks). International Index of Erectile Function (IIEF-5) and International
      Prostate Symptom score (I-PSS) were addressed to the patients during the
      treatment schedule (at fourth or fifth instillation) and 1 month after the last
      instillation. The mean IIEF-5 score was 17.6 +/- 6.7 during therapy and 21.7 +/-
      2.92 a month after the last instillation (P=0.008). Baseline ED and the
      association with lower urinary tract symptoms are variables significantly
      connected with post-treatment results (P=0.016 and 0.00 respectively) whereas the
      age seems not to be related to ED (P=0.256). No major side effects were recorded.
      It is concluded that BCG treatment is effective for prophylaxis of non-muscle
      invasive bladder cancer; however, it may induce a high incidence of ED. Although
      this effect is transient and reversible, erectile failure is another source of
      psychological distress that adversely affects the quality of life of men
      undergoing BCG treatment.

PMID- 17430424
TI  - Effect of pH on the development of acrosomal responsiveness of human sperm.
AB  - Human sperm incubated in vitro gradually become responsive to inducers of the
      acrosome reaction. The roles of constituents of the incubation medium are not
      well understood. These experiments tested the effect of the extracellular pH on
      sperm acrosomal responsiveness. Sperm were incubated 24 h in media with pH
      varying between 6.7 and 7.6 and then exposed to progesterone to determine the
      number of sperm that had become acrosomally responsive. The number of responsive
      sperm was very low following incubation at pH 6.7-7.0, and increased with the pH
      over the range 7.0-7.6. Sperm incubated at low pH were not damaged as assessed by
      motility or viability, and if they were transferred to medium of high pH for 8 h,
      the inhibition of acrosomal responsiveness was reversed. Inhibition of acrosomal
      responsiveness at low pH was not due to impaired loss of sperm cholesterol, but
      was correlated with a reduced intracellular pH. The inhibition of acrosomal
      responsiveness by media of low pH may result from preventing the normal
      capacitation-related rise in intracellular pH.

PMID- 17430425
TI  - Seminal plasma albumin: origin and relation to the male reproductive parameters.
AB  - We wanted to investigate the origin of seminal plasma albumin and its relation to
      the male reproductive parameters. Semen samples from 916 men, under infertility
      assessment, were analysed according to guidelines of the World Health
      Organization. Seminal plasma constituents, i.e. albumin, markers of the
      epididymal (neutral alpha-glucosidase, NAG), prostatic (prostate-specific
      antigen, PSA, and zinc) and seminal vesicle function (fructose), as well as
      levels of reproductive hormones in plasma were measured. The sperm chromatin
      structure assay (SCSA) was applied on 267 of the 916 samples. A negative
      correlation was seen for seminal albumin and plasma follicle-stimulating hormone
      (r=-0.1, P=0.02) and a positive correlation for seminal albumin and serum inhibin
      B (r=0.2, P=0.004). Albumin exhibited positive correlations with the epididymal
      marker, NAG (r=0.5, P<0.001) and with the prostatic markers, PSA and zinc (r=0.1,
      P=0.001; r=0.2, P<0.001 respectively) as well as with age (r=0.2, P<0.001). A
      negative significant association was seen for seminal albumin and semen volume
      (beta=-0.60; 95% CI -0.80 to -0.30). The opposite trend was found regarding sperm
      concentration (beta=0.34; 95% CI 0.30-0.40), total sperm count (beta=0.30; 95% CI
      0.20-0.40), and percentage morphologically normal spermatozoa (beta=0.70; 95% CI
      0.10-1.0). No association was found between albumin and sperm motility, SCSA
      parameters, or fructose, the marker of seminal vesicles. Our results suggest
      testicular, epididymal and prostatic origin of seminal plasma albumin, in
      addition to the contribution from blood. This is the first study to demonstrate
      an association between seminal plasma albumin and sperm morphology. Further
      studies are needed to elucidate the role of seminal albumin in sperm morphology.

PMID- 17430426
TI  - Oral phosphodiesterase-5 inhibitors: effect of heme oxygenase inhibition on cGMP
      signalling in rat cavernous tissue.
AB  - This work postulated that heme oxygenase (HO) is partly responsible for
      controlling phosphodiesterase-5 inhibitor actions by modulating cyclic guanosine
      monophosphate (cGMP) cavernous tissue levels. Five hundred and four male Sprague
      Dawley rats, divided into five groups, were investigated. Group 1 (n=72) included
      controls, group 2 (n=72) received sildenafil citrate (Viagra) orally, group 3
      (n=72) received vardenafil hydrochloride (Levitra), group 4 (n=72) received
      tadalafil (Cialis). Group 5 (n=216), subdivided into three subgroups (A, B and C,
      72 each), received the same dose of each drug with the HO inhibitor, Zn
      protoporphyrin. Eight rats from each group/subgroup were killed at 0.5, 1, 2, 3,
      4, 6, 18, 24 and 36 h when cGMP levels in the cavernous tissues were estimated.
      Cavernous tissue cGMP levels increased significantly in sildenafil, vardenafil
      and tadalafil-treated rats compared to the controls with significant decreases
      after HO inhibition. It is concluded that the effects of these PDE-5 inhibitors
      in rat cavernous tissue are partly mediated through HO activity via the cGMP
      signalling pathway.

PMID- 17430427
TI  - Spontaneous and prolonged drug-induced erection in a patient with inflatable
      penile implant.
AB  - Achievement of spontaneous tumescence after penile implant surgery has already
      been reported. However, regular spontaneous full, rigid erection upon sexual
      arousal that is adequate for vaginal penetration and tumescence for satisfactory
      sexual performance is an extremely rare condition in men with three-piece
      hydraulic implants. Similarly, prolonged erection is not expected in such implant
      cases even with the use of erectogenic agents. We report this interesting
      phenomenon confirmed by magnetic resonance imaging technique in a patient with
      inflatable device.

PMID- 17430431
TI  - In what grade should backpack safety education begin in schools?

PMID- 17430433
TI  - Response to "Parents' perceptions of curricular issues affecting children's
      weight in elementary schools".

PMID- 17430434
TI  - Noise and hearing loss: a review.
AB  - BACKGROUND: Noise-induced hearing loss is a major cause of deafness and hearing
      impairment in the United States. Though genetics and advanced age are major risk
      factors, temporary and permanent hearing impairments are becoming more common
      among young adults and children especially with the increased exposure to
      portable music players. Though treatment options are limited for most people with
      noise-related hearing loss, several modifiable health behaviors that should begin
      in childhood might prevent or delay the onset of hearing impairment. The purpose
      of this article is to review modifiable and non-modifiable risk factors,
      comorbidity, and the role of health education in the prevention of noise-induced
      hearing loss. METHODS: Review of current literature in the etiology, prevention,
      and treatment of noise-induced hearing loss as well as the role of health
      education. RESULTS: Non-modifiable risk factors related to noise-related hearing
      loss include increasing age, genetics, male gender, and race. Modifiable risk
      factors are voluntary exposure to loud noise, nonuse of hearing protection,
      smoking, lack of exercise, poor diet, tooth loss, and the presence of diabetes
      and cardiovascular disease. CONCLUSIONS: As hearing impairment among children and
      teenagers rises due to mostly voluntary exposure to loud noise, there are many
      implications for health education. Health educators need to address barriers to
      the use of hearing protection, deliberate exposure to loud music, and other
      modifiable risk factors, which cause and exacerbate hearing loss among those
      exposed to loud noise.

PMID- 17430435
TI  - Association of relative backpack weight with reported pain, pain sites, medical
      utilization, and lost school time in children and adolescents.
AB  - BACKGROUND: There is debate about a 10% versus 15% of body weight cutoff point
      for safe weight of school backpacks. Estimation of the cutoff may be affected by
      use of survey methods and failure to assess pain experienced while wearing a
      backpack. Previous research also suggests that younger students and females are
      more at risk for developing backpack pain. METHODS: Five hundred and thirty-one
      5th- to 12th-grade Northern California students and their backpacks were weighed.
      Students were individually interviewed about how often they experienced pain
      while carrying a backpack, the site of their pain, and if the pain had interfered
      with school activities or led to medical care. RESULTS: Data support the use of a
      10% of body weight cutoff for safe use of backpacks for all grade levels. Younger
      students and females are more at risk due to relatively lower body weight while
      females also carry heavier backpacks than males. Greater relative backpack weight
      is associated with upper- and mid-back pain reports but not neck or lower back
      pain; it is also associated with lost school time, lost school sports time, and
      greater chiropractic utilization. CONCLUSIONS: The 10% cutoff is recommended
      along with a variety of practical methods to help schools achieve that goal for
      middle and high school students.

PMID- 17430436
TI  - The working postures among schoolchildren--a controlled intervention study on the
      effects of newly designed workstations.
AB  - BACKGROUND: School workstations are often inappropriate in not offering an
      optimal sitting posture. The aim of this study was to investigate the effects of
      individually adjustable saddle-type chairs with wheels and desks with comfort
      curve and arm support on schoolchildren's working postures compared to
      conventional workstations. METHODS: Ninety-seven participants aged 12-16 years
      were followed for 1 year, 47 at an intervention school and 50 at a control
      school. Anthropometrics and workstation dimensions were measured and working
      postures analyzed for a part of each group (n = 21, both groups) by means of
      video recording at baseline, before new workstations were introduced, and during
      follow-up. RESULTS: There was a significant increase in upright back (p= .012)
      and neck (p= .019) postures in the intervention group compared to controls during
      follow-up. The saddle-type chairs allowed significantly greater trunk-thigh
      angles (p < .001) among participants than conventional chairs. CONCLUSIONS: In
      schoolchildren, using individually adjustable saddle-type chairs and desks with
      comfort curve, a better match between workstations and anthropometric dimensions
      and improved working postures are obtained than using conventional workstations.

PMID- 17430437
TI  - Chronic pain in the classroom: teachers' attributions about the causes of chronic
      pain.
AB  - BACKGROUND: School absenteeism and other impairments in school function are
      significant problems among children with chronic pain syndromes; yet, little is
      known about how chronic pain is perceived in the school setting. The purpose of
      this study was to examine teachers' attributions about the causes of chronic pain
      in adolescent students. METHODS: Classroom teachers (n = 260) read vignettes
      describing a hypothetical student with limb pain. They were presented with a list
      of possible physical and psychological causes for the pain and asked to identify
      the causes to which they attributed the pain. Vignettes varied by the presence or
      absence of (1) documented medical evidence for the pain and (2) communication
      from the medical team. Teachers also responded to questions assessing their
      responses to the student in terms of support for academic accommodations and
      sympathy for the student. RESULTS: Teachers tended to endorse a dualistic (ie,
      either physical or psychological) model for pain rather than a biopsychosocial
      model. Documented medical evidence supporting the pain was the most influential
      factor affecting teachers' attributions about chronic pain. Teachers who
      attributed the pain to physical causes-either in isolation or in combination with
      psychological causes-responded more positively toward the student. CONCLUSIONS:
      Many teachers lack a biopsychosocial framework through which to understand
      chronic pain syndromes in students. How chronic pain is described to school
      personnel may affect how teachers understand the pain and respond to it.

PMID- 17430438
TI  - School counselors and student self-injury.
AB  - BACKGROUND: The purpose of this study was to examine the experience, knowledge,
      and needs of school counselors in relation to students' self-injurious behaviors.
      METHODS: One thousand members of the American School Counselor Association were
      randomly selected to receive a questionnaire on the study of self-injury. Four
      hundred forty-three school counselors returned usable questionnaires. RESULTS:
      Most (81%) reported working with a self-injurer during their career, and 51%
      reported working with a self-injurer during the 2002-2003 school year. Findings
      suggest that counselors feel they are the appropriate person to work with
      students who self-injure but need more training to identify self-injurers and
      refer them to appropriate resources outside of the school. Counselors identified
      a number of barriers to successfully working with students who self-injure, such
      as lack of training, lack of cooperation with school personnel, and lack of
      policy on school injury. CONCLUSIONS: The authors suggest a model where the
      school counselor acts as a liaison to ensure the coordination of education about
      self-injury for students, parents, and school staff and as a conduit to refer
      students to therapists in the community.

PMID- 17430439
TI  - Primary grade teachers' perceptions and practices regarding pedestrian safety
      education.
AB  - BACKGROUND: Pedestrian injury is the third leading cause of unintentional injury
      and death among children 1-14 years old. The purpose of this study was to examine
      primary grade teachers' perceived role in pedestrian safety education. METHODS: A
      total of 630 surveys were sent to a national random sample of primary school
      teachers and 54% responded. RESULTS: The results of the study found that 85% of
      primary grade teachers believed it was extremely important or important to teach
      pedestrian safety. Forty percent of the teachers identified that they had been
      teaching pedestrian safety for more than 1 year (maintenance stage), whereas 1 in
      3 teachers had never thought about (precontemplation stage) teaching pedestrian
      safety to their students. Eighty-eight percent of primary grade teachers were
      very confident about teaching students how to safely cross the street, where to
      safely cross the street (87%), when to safely cross the street (86%), and how to
      safely walk along streets with sidewalks (83%). An examination of how pedestrian
      safety information was presented found that a plurality (39%) of the teachers who
      taught pedestrian safety presented information through classroom discussion.
      Also, 46% of the teachers who taught pedestrian safety identified the following
      as the most common curriculum content: when to safely cross the street (46%), how
      to safely cross the street (45%), and where to safely cross the street (43%).
      CONCLUSIONS: Only 16% of primary school teachers reported pedestrian safety
      education was required for their grade levels. Yet, pedestrian safety education
      decreases pedestrian-related deaths. Therefore, it is important for schools and
      primary grade teachers to expose their students to this essential topic.

PMID- 17430440
TI  - Legal liability: the consequences of school injury.
AB  - BACKGROUND: Approximately 10-25% of child and adolescent injuries occur at
      school. Little is known about school-related injuries to teachers and other
      adults or about the direct cost of injuries to schools. This study examined the
      characteristics of cases involving injuries resulting in lawsuits against
      schools, compared cases in which schools paid awards with those in which schools
      did not pay awards, and compared student and nonstudent injuries resulting in
      lawsuits against schools. METHODS: Descriptions of cases of school liability for
      personal injury that were tried or settled between July 1996 and May 2002 were
      purchased from Jury Verdict Research, which maintains a national database of
      verdicts and settlements. The 455 cases reviewed were coded according to the
      characteristics of the case, school, award, and injured party. RESULTS: In two
      thirds of the cases, schools or school districts paid an award to plaintiffs
      (mean =$562,915, median =$50,000). In most cases, the injured party was male
      (57.1%) and younger than 18 years of age (79.9%). Fractures (38.9%) were the most
      common type of injury. Falls (21.9%) were the most common cause of injury. Among
      cases of intentional injury, 93.2% involved an injury to a student; among cases
      of unintentional injury, 74.6% involved injury to a student. CONCLUSIONS:
      Preventing school-related injuries is an ethical and legal obligation for schools
      and school districts. Prevention is also critical because a wide range of
      injuries are litigated, and such lawsuits often require schools and school
      districts to pay costly awards to injured parties.

PMID- 17430443
TI  - The personal must be the political: how and why.

PMID- 17430444
TI  - Trialling of the Partnership in Coping System.
AB  - The paper describes the results of a preliminary trial of a system of mental
      health nursing, the Partnership in Coping system, based on the subjective
      experiences of the participating mental health nurses and service users. The
      community mental health study involved action research, with data being collected
      through individual interviews and focus groups. Data analysis, using thematic
      content analysis, resulted in the emergence of two main dimensions. These
      dimensions are centred around a shift in responsibility from the service to the
      service user, and the authentication and clarification of the roles of the nurse
      and the service user.

PMID- 17430445
TI  - Using the chronic care model to tackle depression among older adults who have
      long-term physical conditions.
AB  - Effective psychological and pharmacological treatments are available, but for
      depressed older adults with long-term physical conditions, the outcome of routine
      care is generally poor. This paper introduces the chronic care model, a systemic
      approach to quality improvement and service redesign, which was developed by Ed
      Wagner and colleagues. The model highlights six key areas that need to be
      addressed, if depression is to be tackled more effectively in this neglected
      patient group: delivery system design, patient-provider relationships, decision
      support, clinical information systems, community resources and healthcare
      organization. Three influential programmes, the Improving Mood Promoting Access
      to Collaborative Treatment programme, the Prevention of Suicide in Primary Care
      Elderly Collaborative Trial, and the Program to Encourage Active, and Rewarding
      Lives for Seniors, have shown that when the model is adopted, significant
      improvements in outcomes can be achieved. The paper concludes with a case study,
      which illustrates the difference that adopting the chronic care model can make.
      Radical changes in working practices may be required, to implement the model in
      practice. However, Greg Simon, a leading researcher in the field of depression
      care, has suggested that there is already sufficient evidence to justify a shift
      in emphasis from research towards dissemination and implementation.

PMID- 17430446
TI  - The Bali bombings and the evolving mental health response to disaster in
      Australia: lessons from Darwin.
AB  - The Bali bombing in 2002 initiated a new phase of trauma response for public
      health services in Australia, and the Royal Darwin Hospital in particular. The
      mental health response to the initial disaster was limited to a debriefing of
      Royal Darwin Hospital staff some time after the disaster. Following this initial
      episode, a number of important developments occurred within the Royal Darwin
      Hospital and nationally to further develop mental health resources. A mental
      health consultation liaison nursing position was established within the hospital.
      The Director of Mental Health for the Northern Territory, along with the Director
      of Psychiatry, was involved with an evolving national mental health response to
      mass trauma through the National Planning Group of Mental Health Response to
      Trauma. The improved recognition of mental health in disaster response, along
      with increased recognition and confidence in the consultation liaison nursing
      staff, considerably improved the mental health services available to patients and
      Royal Darwin Hospital staff following the second Bali blast in October 2005.

PMID- 17430447
TI  - Mental health triage: towards a model for nursing practice.
AB  - Mental health triage/duty services play a pivotal role in the current framework
      for mental health service delivery in Victoria and other states of Australia.
      Australia is not alone in its increasing reliance on mental health triage as a
      model of psychiatric service provision; at a global level, there appears to be an
      emerging trend to utilize mental health triage services staffed by nurses as a
      cost-effective means of providing mental health care to large populations. At
      present, nurses comprise the greater proportion of the mental health triage
      workforce in Victoria and, as such, are performing the majority of point-of-entry
      mental health assessment across the state. Although mental health triage/duty
      services have been operational for nearly a decade in some regional healthcare
      sectors of Victoria, there is little local or international research on the
      topic, and therefore a paucity of established theory to inform and guide mental
      health triage practice and professional development. The discussion in this paper
      draws on the findings and recommendations of PhD research into mental health
      triage nursing in Victoria, to raise discussion on the need to develop
      theoretical models to inform and guide nursing practice. The paper concludes by
      presenting a provisional model for mental health triage nursing practice.

PMID- 17430448
TI  - Time geography: a model for psychiatric life charting?
AB  - Since many years, life charting has been used to describe the life course and
      life events of psychiatric patients. The aim of the present study was to describe
      and evaluate time geographic life charts of 11 former psychiatric patients in
      order to promote systematic descriptions of their life events over time.
      Information on all events which was gathered from the life charts was analysed by
      manifest content analysis and reduced to four categories: information received by
      asking only about moves, social capacity, predisposing life events and/or
      stressful as well as precipitating life events. Our findings showed that this
      kind of life charts offered a comprehensive and structured picture. They describe
      a detailed life situation from one time period to another, where geographical
      sites serve as anchors. The patients expressed satisfaction with this method of
      combining an interview with a time geographic life line.

PMID- 17430449
TI  - The role of the nurse prescriber: the views of mental health and non-mental
      health nurses.
AB  - Even though the introduction of the role of the nurse prescriber promises
      improved access to medicines and increased flexibility in the workforce, the take
      up of this role to date has been variable across the UK. This questionnaire-based
      study sought to compare the expectations of two distinct groups of nurses, one
      from a mental health and the other from a non-mental health background prior to
      becoming prescribers. Non-mental health nurses were of the opinion that being
      able to prescribe would increase efficiency and maximize resources, while mental
      health nurses saw prescribing primarily in terms of the benefits to clients-
      increased choice, improved access to care, better information about treatments
      and better quality of care.

PMID- 17430450
TI  - Expressed emotion and burnout: the experience of staff caring for men with
      learning disability and psychosis in a medium secure setting.
AB  - This study examines the level of expressed emotion (EE) and burnout in staff
      caring for people with learning disabilities on a medium secure unit. The study
      aims to develop a baseline measure of EE and burnout in staff on the unit to be
      used for future service evaluation and to underpin interventions in the
      developing service based on psychosocial interventions. Ten staff participated in
      an audiotaped interview and completed a questionnaire. The Five Minute Speech
      Sample and Maslach Burnout Inventory were completed. High EE was evident in 31%
      of responses based on critical comments and negative relationships. Expressed
      emotion was higher in male staff and in Health Care Support Workers. No staff met
      all components for high burnout, but low personal accomplishment, high emotional
      exhaustion and high depersonalization were evident for some staff. There is
      evidence of high EE and some elements of high burnout within the staff team. A
      significant relationship was found between the level of high EE and the
      depersonalization element of burnout.

PMID- 17430451
TI  - Modernity, mental illness and the crisis of meaning.
AB  - Western civilization has, over its relatively recent past, undergone dramatic,
      unparalleled changes. The historical period in which these changes have occurred
      is commonly referred to as 'modernity', and although modernity has had profound
      repercussions on all aspects of people's lives, what has received less attention
      in the nursing literature is how modernity has influenced, and continues to
      influence, the mental health of modern men and women. In an attempt to address
      this, the following paper, drawing on the work of Szasz, Nietzsche and Frankl,
      seeks to present an accessible introduction to one of the most salient features
      of modernity; namely, the erosion of those traditions that gave life a meaning or
      a purpose, and that provided people with ready answers to the problem of how they
      ought to live. The paper will then introduce some of the possible consequences of
      this on the mental health of modern men and women, as well as providing
      preliminary suggestions as to how mental health nursing might respond. In doing
      so, the paper also seeks to stimulate further discussion and research into how
      modernity has influenced, and continues to influence, the mental health of modern
      men and women, and how psychiatric and mental health nursing might respond.

PMID- 17430452
TI  - Developing services for the carers of young adults with early-onset psychosis -
      implementing evidence-based practice on psycho-educational family intervention.
AB  - This paper describes a series of practice and service development initiatives to
      incorporate the family-inclusive approach into the newly established Early
      Intervention in Psychosis Service in Berkshire, England. Following a local study
      on carers' experiences and needs from those who cared for a young adult with a
      first-episode psychosis (FEP), a series of flexible services for this group of
      carers has been developed incorporating the much-researched psycho-educational
      family interventions. The findings of our local phenomenological study on the
      carers for young adults with FEP clearly specified the unique needs of this group
      of carers and that well-established approaches in family work and carers support
      facilities may have to be adapted to meet such needs. This paper reports the
      service development process through which a series of specially designed carers'
      services were set up for carers caring for a young adult with FEP. These services
      were developed to address carers' needs for knowledge, skills and support to cope
      with their caring roles and situation, from the stressful beginning of a
      potentially long caring journey.

PMID- 17430453
TI  - Exploring the feasibility of email-mediated interaction in survivors of abuse.
AB  - There is a growing use of email-based provision of information, development of
      health-related skills and interventions; however, use of email to assist women
      and children experiencing abuse after receiving Protection from Abuse (PFA) court
      order has not been explored. The specific aim of this research was to test the
      feasibility of an email device called MIVO for use in interacting with women and
      children after receiving PFA. This qualitative design used a three-step
      recruitment, screening and email interaction with mothers and their adolescent
      child after obtaining informed consent and training in the use of an email
      device. Sample included six pairs of mother and child (n = 12) who have received
      a PFA within the past 6 months. Demographic data were gathered using the
      sociodemographic questionnaire. Qualitative data were gathered using email
      messages from mother and child pairs. Results showed that email interaction is a
      feasible and acceptable way of providing support and information to survivors of
      abuse after their PFA. The following themes in their order and rank of appearance
      were found in the email interaction between the nurse and survivors: (1) safety
      issues; (2) job-related issues; (3) school-related issues; (4) parenting-related
      issues; and (5) health-related issues. Themes identified for the children were
      school work and friends. Privacy, confidentiality and respect for individual
      rights are paramount in email interactions. Email interaction is useful in
      education, screening, safety instructions and follow-up care. Technological
      devices such as MIVO may have usefulness as an email interaction device among
      women, their child and a nurse to reduce their risk for further interpersonal
      violence/abuse and to increase disclosure of abuse. Healthcare providers need to
      identify technological developments, and through evidence-based research examine
      their feasibility and adaptability for translation into practice specifically, in
      caring for survivors of abuse.

PMID- 17430454
TI  - Stigmatization by nurses against schizophrenia in Turkey: a questionnaire survey.
AB  - Individuals who have been diagnosed with schizophrenia face discrimination,
      exclusion and stigmatization by society. Nurses who work on psychiatric wards
      frequently face individuals diagnosed with schizophrenia throughout their
      careers. This study was conducted for the purpose of evaluating nurses' opinions
      about individuals who had been diagnosed with schizophrenia. A total of 543
      nurses working on the psychiatric wards of 27 university hospitals (164), six
      training and research hospitals (21) and six psychiatric hospitals (358) in
      Turkey completed the questionnaire. The majority of the nurses stated that
      schizophrenia is caused by social problems, that they would be able to work with
      someone who has schizophrenia, that they would not be able to marry someone with
      schizophrenia, that they would not be bothered by having a neighbour with
      schizophrenia, that schizophrenia cannot be completely cured, that it can be
      improved with psychotherapy, that schizophrenic patients are aggressive and that
      medications used to treat schizophrenia have serious side effects and are
      addictive. It is important for nurses to avoid stigmatizing patients in order to
      promote a therapeutic environment--particularly on the wards--and also to improve
      individual awareness and perceptions in society.

PMID- 17430455
TI  - Mental health crisis at home: service user perspectives on what helps and what
      hinders.
AB  - This paper presents data which emerged during the process of a participatory
      research study to identify the perspectives of previous users of a home treatment
      service. Feedback was sought in order to establish the criteria for the
      development of a service evaluation questionnaire. Seven themes emerged from the
      data which were then used as a framework for the evaluation questionnaire. These
      themes have also been used within this paper to present what our participants
      told us was important to them when they received a service at home at a time of
      mental health crisis. Although what is described here is the experience of one
      group of service users in the North of England, we hope that the views of these
      participants will create a resonance with providers of other home treatment
      services and expand the knowledge about which aspects of care at home during
      mental health crisis are viewed as helpful and those aspects which are not.

PMID- 17430461
TI  - Abstracts from the American Geriatrics Society 2007 Annual Scientific Meeting.
      May 2-6, 2007. Seattle, Washington, USA.

PMID- 17430456
TI  - Replicability and stability of the multidimensional model of the Edinburgh
      Postnatal Depression Scale in late pregnancy.
AB  - The Edinburgh Postnatal Depression Scale (EPDS) is a widely used screening tool
      for post-natal depression (PND). Recent factor analytic investigations of the
      EPDS have suggested the instrument may be useful in the prediction of PND as the
      instrument appears to be multidimensional, thus facilitating sub-scale
      development for this purpose. The psychometric properties of the EPDS were
      evaluated in women in the third trimester of pregnancy. Confirmatory factor
      analyses found support for the multidimensionality of the instrument; however,
      there was clear variability in model fit to data suggesting previous reports of
      the stability of the underlying factor structure of this instrument may be over
      optimistic. The potential for development of the EPDS as a predictive screening
      measure of PND is likely to be optimistic because of variability in the factor
      structure of the instrument over the course of pregnancy and in the post-natal
      period.

PMID- 17430462
TI  - Pre-operative predeposit autologous donation in children presenting for elective
      surgery: a review.
AB  - Predeposit Autologous blood donation (PAD) in children decreases the life-time
      complications associated with allogeneic blood. These complications include
      transmission of known or unknown pathogens and alloimmunization against future
      blood transfusions, organ transplants and pregnancies. In view of the potential
      long term benefits of PAD should it be considered a component of paediatric blood
      conservation programs. This paper reviews the literature to explore the risk of
      benefit analysis of adopting PAD in paediatric practice.

PMID- 17430463
TI  - Attitudes towards blood donation in Trinidad and Tobago.
AB  - The aims of this study were to determine the factors that influence blood
      donation in different demographic groups in a multi-ethnic, multicultural
      community, and to devise a strategy for a national campaign to increase voluntary
      non-remunerated blood donations. The majority (87%) of blood donations in
      Trinidad and Tobago are replacement donations. Seventy per cent of the country's
      transfusion needs are not met. In 1998, the World Health Assembly recommended
      that reliance on replacement donations should be phased out due to their
      association with an increased risk of transfusion-transmitted infections. An
      observer-administered questionnaire was completed by 1423 respondents in a multi
      ethnic borough in central Trinidad. Respondents were classified as donors or non
      donors and grouped by age, race, religion, employment status and highest level of
      education. The prevalence of a history of blood donation and the factors that
      encouraged donation or conversely discouraged donation in each demographic group
      were recorded. A total of 1146 (81.2%) respondents had never donated blood. Of
      the 277 (18.8%) who had previously donated, replacement for a family member or
      friend was the most common reason (86.9%). The prevalence of donation was low in
      all racial, religious, gender, educational and age groups. However, there were
      significant demographic variations. The majority (71.3%) of non-donors cited a
      lack of information as a major reason for non-donation and expressed a
      willingness to donate if access to information and donation facilities were
      improved. Voluntary blood donation in Trinidad and Tobago could be greatly
      increased by a national education campaign and increased accessibility to
      donation centres. This would ensure a safer and more reliable blood supply.

PMID- 17430464
TI  - Processing of stored packed red blood cells using autotransfusion devices
      decreases potassium and microaggregates: a prospective, randomized, single
      blinded in vitro study.
AB  - The aim of the study was to compare the potential of autotransfusion devices to
      reduce non-infectious complications related to transfusion of long-stored packed
      red blood cells (PRBC; n= 57), such as changes in electrolytes, blood cells and
      the load of free microaggregates. Following a baseline measurement, a blood pool
      of three PRBC was divided into three equal volumes and washed with either the
      Haemonetics Cell Saver (HCS) or the continuous autotransfusion system (C.A.T.S),
      using the quality (CATS(quality)) and emergency (CATS(emergency)) mode. After the
      washing procedure, measurements for electrolytes, blood cells and free
      microaggregates were repeated (n= 19 each). Compared with baseline, the
      investigated autotransfusion devices reduced the median load of potassium
      (baseline: 52 mEq L(-1); HCS: 4 mEq L(-1); CATS(quality): 4 mEq L(-1);
      CATS(emergency): 17 mEq L(-1); each P < 0.001), restored a physiologic
      electrolyte balance and significantly decreased the load of leucocytes, glucose
      and protein. Whereas the quantity of microaggregates was not reduced by HCS,
      CATS(emergency) decreased the load of cell fragments below 7.8 microm (P < 0.05
      vs. baseline). Using CATS(quality) decreased the load of cell fragments not only
      to a diameter below 7.8 microm (P < 0.001 vs. baseline) but also of
      microaggregates between 7.8 and 17.6 microm (P < 0.05 vs. baseline). In
      situations where long-stored PRBC have to be transfused, the procedure described
      here may be feasible to reduce clinically relevant side effects, i.e.
      hyperkalaemia and microvascular obstruction secondary to free cell fragments.
      This approach could be especially useful in patients undergoing massive
      transfusion and/or suffering from renal failure.

PMID- 17430465
TI  - Rapid and accurate measurement of anti-A/B IgG antibody in ABO-unmatched living
      donor liver transplantation by surface plasmon resonance.
AB  - High anti-blood group A or B (anti-A/B) immunoglobulin G (IgG) haemagglutination
      titres are associated with poor graft survival in ABO-unmatched liver
      transplantation. We have previously reported that the surface plasmon resonance
      (SPR) method can be used to measure anti-A/B IgG levels in the plasma very
      quickly and quantitatively. The aim of this study was to brush up this SPR
      method. The anti-A/B IgG antibodies (Abs) were purified from the plasma of
      healthy volunteers by affinity chromatography and used to establish standard
      curves for the SPR and flow cytometry (FCM) methods. The haemagglutination test
      tube (TT), FCM and SPR methods were then used to measure the changes over time in
      the anti-A/B IgG titres of 25 ABO-unmatched living donor liver transplantation
      (LDLT) recipients. The standard curve permitted the SPR values for the anti-A/B
      IgG titres to be expressed in microg mL(-1) units. The SPR measurements of the
      anti-A/B IgG levels in the LDLT recipients correlated very well with the FCM
      values, whereas the TT values correlated poorly with either method. Furthermore,
      the SPR method accurately detected the effects of plasma exchange. In conclusion,
      the SPR method is an accurate, time- and labour-saving method for measuring anti
      A/B IgG titres that can be easily standardized.

PMID- 17430466
TI  - Collection strategies and cryopreservation of umbilical cord blood.
AB  - The aim of this study was to compare (a) two different umbilical cord blood (UCB)
      collection methods while the placenta is still in the uterus (in utero), and (b)
      to evaluate the efficacy of four cryopreservation protocols based on UCB
      haematopoiestic stem cell (HSC) recovery. We analysed UCB samples collected with
      our original collection system designed for active Syringe/Flush/Syringe method
      or by standard in utero method. For comparing different cryopreservation
      procedures, dimethyl sulphoxide (DMSO) at final concentration of 5 and 10% was
      used and combined with our own controlled-rate or uncontrolled-rate
      cryopreservation. A total of 99 samples were collected. A significantly higher
      UCB volume, total nucleated cell and mononuclear cell were seen following the
      first collection strategy (n= 49; mean +/- SD, 103 +/- 35.4 mL; 12.34 +/- 5.27 x
      10(8); 595 +/- 3.47 x 10(6)) vs. the second strategy (n= 50; 86 +/- 29.3 mL; 9.87
      +/- 4.47; 424 +/- 2.82 x 10(6)) respectively (P < 0.01). The discard rate was 14%
      for the first and 36% for the second collection strategy (P < 0.01). It was shown
      that the most efficient procedure was the controlled-rate protocol combined with
      lower (5%) DMSO concentration. Using active Syringe/Flush/Syringe method, we
      collected UCB with greater volumes and with lower discard rate compared to the
      standard by gravity technique. The data presented also showed much better
      recovery of UCB cells when controlled-rate freezing procedure and 5% DMSO were
      combined.

PMID- 17430467
TI  - Effect of packed red blood cells transfusion on plasma fibronectin during liver
      resection.
AB  - Our study aimed at evaluating the effect of blood transfusion - allogeneic or
      autologous - on plasma levels of fibronectin during liver resections. Thirty-five
      patients scheduled for liver resection were randomly allocated to receive
      autologous (group autologous blood transfusion (ABT), n= 19) or allogeneic
      (homologous) (homologous blood transfusion (HBT), n= 16) packed red blood cell to
      maintain serum haemoglobin concentration above 9 g. Serum levels of fibronectin
      were measured before induction of anaesthesia, at the end of operation and at
      first, third and sixth postoperative day. Perioperative morbidity and survival
      rate were also recorded. Serum fibronectin levels were significantly higher (P <
      0.05) in the autologous group than in the allogeneic, at the first (134 +/- 49
      microg mL(-1) vs. 89 +/- 31 microg mL(-1)) and third (178 +/- 51 microg mL(-1)
      vs. 96 +/- 41 microg mL(-1)) postoperative day. No differences in survival and
      complication rate between the two groups were observed. Concentrations of serum
      fibronectin seem to be adversely affected by allogeneic blood transfusion during
      liver resection surgery, although this does not seem to affect patients'
      morbidity and mortality.

PMID- 17430468
TI  - Effect of extending the platelet storage time on platelet utilization:
      predictions from a mathematical model of prophylactic platelet support.
AB  - Bacterial culturing (BCU) or photochemical treatment (PCT) of platelet (PLT)
      concentrates may permit extending the storage time to 7 days at the cost of
      decreased viability of transfused PLTs. This study was aimed at predicting the
      impact this may have on the routine management of patients on prophylactic PLT
      support. The method included a mathematical model that represents the dynamics of
      prophylactic PLT support with standard, BCU or PCT PLTs. Data on posttransfusion
      PLT kinetics and the effect of PCT or storage time on PLT recovery and survival
      were obtained from published studies. Variables that influenced the level of PLT
      usage were the proportion of transfusions supplied with PLT on the last day of
      shelf-life, the use of PCT and the assumed degree of synergy between clinical
      factors of PLT consumption and either PCT or storage time. In the reference-case
      scenario, extending the PLT shelf-life to 7 days by BCU or PCT increased by 9 and
      19%, respectively, the number of PLT transfusions per patient-year. In the worst
      case scenario, these figures rose to 27 and 38%, respectively. Despite more
      intensive PLT usage, in most scenarios, the time that patients spent at PLT
      counts <10 x 10(9) L(-1) increased. Extending the shelf-life of PLT products will
      increase PLT usage. Such increase may be disproportionately larger for patients
      with complex conditions if there is a synergic interaction between storage time
      or PCT and clinical factors of PLT consumption, an issue that is worth further
      clinical research.

PMID- 17430469
TI  - Role of anti-human leucocyte antigen class II alloantibody and monocytes in
      development of transfusion-related acute lung injury.
AB  - Recently, evidence implicating the roles of the anti-human leucocyte antigen
      (HLA) class II antibody in the development of transfusion-related acute lung
      injury (TRALI), which is one of the most serious possible side effects of
      transfusion, has been accumulating. The aim of this study is to clarify the roles
      of the anti-HLA DR alloantibody in TRALI development. Cultured human lung
      microvascular endothelial (LME) cells were incubated with either HLA-DR15
      positive or HLA-DR15-negative monocytes together with serum from a single
      multiparous donor previously implicated in a clinical case of TRALI and known to
      contain anti-HLA DR15 antibody. Production of soluble leukotriene B(4) (LTB(4))
      was measured in the supernatant and found to be markedly increased in the
      presence of HLA-DR15-positive monocytes but not with the HLA-DR15-negative
      monocytes or in the absence of LME cells. The vascular cell adhesion molecule-1
      expression in LME cells and leucocyte-function-associated molecule-1 (LFA-1)
      expression in HLA-DR15-positive monocytes were notably enhanced after combined
      culture of LME cells, HLA-DR15-positive monocytes and TRALI-inducing anti-HLA
      DR15 antibody-positive serum. In conclusion, anti-HLA DR alloantibodies may be
      implicated in LME dysfunction that leads to TRALI, in a monocyte-dependent
      manner.

PMID- 17430470
TI  - Blood bank protocols for large-scale civilian casualty events: experience from
      terrorist bombing in Israel.
AB  - Terrorist attacks in crowded places cause multiple casualties that are evacuated
      by quick succession to nearby hospitals. The study goals were to analyse the
      issues of patient misidentification and excessive blood request and to develop
      recommendations for the management of such episodes. A retrospective analysis of
      nine explosion attacks was performed. In nine consecutive events, 450 casualties
      were reported by the National Ambulance Service, 82 of whom (18%) died on the
      explosion site and 368 were admitted to nearby trauma centres. Red blood cell
      units were typed and cross-matched for 70 patients. Seventy-three per cent of the
      blood supplied over the first 24 h was administered during the first 2 h. The
      cross-matched/transfused ratio was 2.52 +/- 1.42, reflecting the overestimation
      of blood requirement in mass casualty episodes. In the mass casualty setup, blood
      bank personnel should be alert to a potential mistransfusion or a blood
      collection error. Unidentified patients are subjected to errors due to only one
      digit difference in their temporary identification number. Application of the
      system using an additional sequential four-digit number printed in bold and large
      size font for patients at admission reduced the possibility of misidentification.
      Modern technologies, including error-reduction design wristbands, barcode-based
      system or radiofrequency identification tags may also increase reliability of
      patient identification in the mass casualty setup.

PMID- 17430471
TI  - Improving compatibility between blood packs and transfusion sets.

PMID- 17430473
TI  - Partial D and weak D: can they be distinguished?

PMID- 17430474
TI  - Nucleic acid amplification testing detection of an HIV-1 infection in a blood
      donor during the preseroconversion window period.

PMID- 17430475
TI  - Value of surveillance biopsy in pediatric heart transplantation.

PMID- 17430476
TI  - Insurance, non-adherence--a call to action.

PMID- 17430477
TI  - Looking beneath the surface of the CYP3A5 polymorphism.

PMID- 17430478
TI  - Ventricular assist devices in children: current achievements and future
      perspectives.
AB  - Mechanical circulatory support systems for the treatment of acute and chronic
      heart failure are now available for use in several clinical situations and are
      designed for different indications and support times. In children, particularly
      in small infants, extracorporeal membrane oxygenation and centrifugal pumps have
      been most widely used in the past. These systems are preferred for support after
      cardiac operations and for use in patients who have concomitant respiratory
      failure, but they are suitable for short-term application only and intensive care
      is obligatory. VADs are designed for long-term application and allow patients to
      be discharged home. Pneumatic pulsatile VADs have been available in pediatric
      sizes since 1992. Currently at our institution, 74 children have been supported
      with pediatric extracorporeal VADs for up to 14 months. In the past five yr, a
      notable rise in survival has been achieved by improvements in pump design and pre
      and post-operative management. We have been able to discharge 78% of the infants
      under one yr old. In this review, our current VAD experience in children will be
      presented in the light of improvements in decision-making, device technology, and
      implantation techniques, and in coagulation monitoring and anticoagulation.
      Additionally, new developments in the field of pediatric assist devices will be
      presented.

PMID- 17430479
TI  - Pediatric liver transplantation in Iran: evaluation of the first 50 cases.
AB  - LT is nowadays accepted as the definitive therapy for end-stage liver disease. We
      report our experiences with pediatric LT using grafts from living related and DD.
      From April 1999 to March 2006, 50 infants and children who underwent LT were
      studied for pretransplantation status, medical and surgical complications and
      survival rate. There were 33 (66%) boys and 17 (34%) girls. The mean age of
      patients was 9.9 +/- 4.8 yr (range: 0.9-17.7) with a mean weight of 33.4 +/- 18.4
      kg (range: 7.5-80). The main indications were cryptogenic cirrhosis (30%),
      autoimmune cirrhosis (24%), followed by biliary atresia (22%), Wilson disease
      (14%), progressive familial intrahepatic cholestasis (4%), fulminant hepatitis
      (4%) and tyrosinemia (2%). We used living-related donor in 14 (28%) and split
      liver in 5 (10%) cases and other patients received whole liver from DD. The mean
      follow-up of patients was 24.7 +/- 22.6 months (range: 1-72). The main
      postoperative complications were acute cellular rejection (44%) and infections
      (30%), whereas chronic rejection was seen in 26% of cases. The mortality rate was
      24%. Overall mean survival (76% alive) was 63.5 +/- 5.7, 95% CI: 52.3-74.6. Our
      results demonstrate that pediatric LT is a feasible undertaking in Iran. Organ
      shortage in our area led to liberal use of living related and split liver
      techniques. The overall results of the pediatric LT in Iran are encouraging.

PMID- 17430480
TI  - Intravenous and oral sequential itraconazole antifungal prophylaxis in paediatric
      stem cell transplantation recipients: a pilot study for evaluation of safety and
      efficacy.
AB  - This single-centre, retrospective, observational pilot study was performed to
      evaluate the safety and efficacy of intravenous and oral itraconazole prophylaxis
      in paediatric haematopoietic stem cell transplantation (HCT). Study end-points
      were proven invasive fungal infection (IFI), survival, adverse reactions and
      graft-vs.-host disease (GVHD); 53 children and one young adult (median age 8.6
      yr; range 0.4-18.3) transplanted between November 2001 and August 2004 were
      included in this study. Itraconazole was given intravenously from day +3 after
      HCT until oral medication became possible and continued until day +100 after HCT.
      Two proven new IFI in the itraconazole group (candidiasis, n = 1; aspergillosis,
      n = 1) were observed. After a median follow-up of 1.6 yr (0.3-6.1), six deaths
      (8%) were seen; 24 patients (45%) developed GVHD degree I-II, three children (6%)
      had GVHD degree III-IV. In 11 of 53 patients (21%), itraconazole prophylaxis was
      discontinued prematurely, mostly because of fever of unknown origin (n = 7). In
      total, 21 of 53 (40%) of the children had abnormal results of laboratory
      investigations during the prophylaxis. The results of this pilot study indicate
      that itraconazole prophylaxis during HCT in children is feasible and safe,
      despite abnormal laboratory results. The efficacy in terms of prevention of IFI,
      however, has to be addressed in a prospective large-scale study.

PMID- 17430481
TI  - Optimizing outcomes for neonatal ARPKD.
AB  - A retrospective analysis was conducted on 10 consecutive cases of neonatal ARPKD,
      9 of whom received kidney transplants (KT). All were diagnosed antenatally (n =
      6) or at birth. In the first month of life 70% required ventilatory support. Pre
      emptive bilateral nephrectomy and peritoneal dialysis (PD) catheter placement
      were performed in 9 at a mean age of 7.8 +/- 11.9 months. The indications for
      nephrectomy were massive kidneys, resulting in suboptimal nutrition and
      respiratory compromise. All patients received assisted enteral nutrition, with
      significant increase in mean tolerated feeds following nephrectomy (p < 0.05),
      with increase in mean normalized weight and height (0.92 and 1.2 delta SDS
      respectively), by one year post-transplantation. KT was performed at a mean age
      and weight of 2.5 +/- 1.4 years and 13.3 +/- 6.1 kg. The mean creatinine
      clearance at one year post-KT was 91.3 +/- 38.1 mls/min/1.73 m(2), with a
      projected graft life expectancy of 18.4 years. Patient survival was 89% and death
      censored graft survival was 100%, at a mean follow-up of 6.1 +/- 4.5 years post
      transplant. Six patients demonstrated evidence of hepatic fibrosis, one of which
      required liver transplantation. In patients with massive kidneys from ARPKD, pre
      emptive bilateral nephrectomy, supportive PD and early aggressive nutrition, can
      minimize early infant mortality, so that subsequent KT can be performed with
      excellent patient and graft survival.

PMID- 17430482
TI  - Psychological well-being in adults transplanted in childhood.
AB  - Few studies have explored the long-term psychological effects on young adults of
      childhood transplants. The aim of the present work was to examine psychological
      adaptation related to self-concept, self-esteem and subjective well-being in
      young adults who had undergone solid organ transplantation in childhood. Twenty
      four adults transplanted in childhood participated in the study (13 of them
      received kidney transplants, five heart transplants and six liver transplants).
      Participants were of both sexes, aged 18-22, and were selected from three public
      hospitals in Madrid. The results reveal no differences in psychological
      adaptation according to the transplant type (kidney, heart, or liver), and a
      significant difference in negative affect between women and men (women present
      more negative affect than men). Hierarchical regression analysis, after
      controlling for possible confounding effects of demographic and clinical
      variables, showed the predictive power of self-esteem to explain positive affect
      (60% of the total variance). Furthermore, physical self-concept, health status
      and time on waiting list explain 71% of the negative affect variance. Our data
      suggest the importance of self-esteem for the positive affect, and the power of
      clinical variables for the negative affect in young adults transplanted in
      childhood.

PMID- 17430483
TI  - Clinical outcomes and graft characteristics in pediatric matched sibling donor
      transplants using granulocyte colony-stimulating factor-primed bone marrow and
      steady-state bone marrow.
AB  - Matched sibling donor (MSD) transplant is a life-saving procedure for children
      with various hematological malignancies and non-malignancies. Traditionally,
      steady-state bone marrow (S-BM) has been used as the source of stem cells. More
      recently, peripheral blood stem cell (PBSC) after granulocyte-colony stimulating
      factor (G-CSF) mobilization has gained popularity. Adult studies of G-CSF-primed
      BM (G-BM) have shown that it produces rapid white blood cell engraftment like
      PBSC, but with less chronic graft-vs.-host disease. No such study has been
      published in pediatric patients. We conducted a pilot clinical trial of G-BM for
      pediatric patients. Ten patients were enrolled and were compared to a
      contemporaneous group of 12 patients who received S-BM. Patients in the G-BM
      group received a higher dose of total nucleated cells/kg (7.01 vs. 3.76 x 10(8),
      p = 0.0009), higher granulocyte-macrophage colony-forming units (CFU-GM)/kg (7.19
      vs. 3.53 x 10(5), p = 0.01) and had shorter inpatient length of stay (28 vs. 40
      days, p = 0.04). The engraftment, transfusion requirement and disease-free
      survival between the two groups were similar. We concluded that G-BM should be
      considered as an alternative graft source to S-BM, with the benefits of larger
      graft cell dose, higher CFU-GM dose and shorter length of stay.

PMID- 17430484
TI  - Unsuspected rejection episodes on routine surveillance endomyocardial biopsy post
      heart transplant in paediatric patients.
AB  - The use of routine endomyocardial biopsies post-heart transplant in children
      remains controversial. It is generally accepted as the gold standard for
      detecting rejection, but details of the surveillance protocol, such as number and
      timing of biopsies, remain uncertain, with suggestions that recent advances in
      immunosuppressant therapy have obviated the need to perform surveillance
      biopsies. We retrospectively analysed results of endomyocardial biopsies
      performed in our unit since the introduction of a policy of three routine
      biopsies in the first six months post-transplantation. We specifically examined
      only routine surveillance biopsies in order to determine whether clinically
      unsuspected cases of rejection were identified. Between January 2002 and April
      2006, 63 children completed three biopsies in the first six months post
      transplant. Of 189 surveillance endomyocardial biopsies, 19 (10%) patients showed
      significant, grade III or above, rejection. One patient had two episodes of
      rejection. In only one case the child was haemodynamically unstable, four cases
      were mildly unwell, and 14 of 19 (74%) cases demonstrated no cardiac symptoms.
      Four of eight cases treated with sirolimus for some part of their post-transplant
      course had an episode of rejection and of 54 tacrolimus-treated patients, 13 had
      an episode of asymptomatic rejection detected. One of the seven infants had
      significant episode of rejection. Asymptomatic, clinically significant rejection
      is detected in about 10% of biopsies overall using a three-biopsy protocol in the
      first six months after paediatric heart transplantation, and occurs in 24% of
      tacrolimus-treated patients. More frequent surveillance appears needed in
      children treated with sirolimus, but less frequent surveillance may be possible
      in infants.

PMID- 17430485
TI  - Reversal of loss of glomerular filtration rate in children with transplant
      nephropathy after switch to everolimus and low-dose cyclosporine A.
AB  - Until now there have been no good therapeutic options in children with biopsy
      proven transplant nephropathy (TN) and loss of glomerular filtration rate (GFR)
      while receiving cyclosporine A (CsA), mycophenolate mofetil (MMF) and
      prednisolone (Pred). In 13 kidney transplanted children (mean age 13 yr, SD 4)
      with CsA/MMF/Pred immunosuppression, renal biopsy revealed significant TN. MMF
      was discontinued, CsA dose was reduced to 50% and Everolimus was started (1.6
      mg/m(2)/day). Pred was stopped in 10 of 13 patients. The mean GFR was 55
      mL/min/1.73 m(2) (SD 24) one yr before switch, 45 mL/min/1.73 m(2) (SD 16, p <
      0.05) at the time of switch and 47 mL/min/1.73 m(2) (SD 18, p < 0.05) 12 months
      later. There were no severe side-effects or acute rejections. Lactate
      dehydrogenase, cholesterol, creatine kinase, and U-albumin/creatinine ratio did
      not increase significantly. After six months, the mean certican-C0 level was 4.0
      microg/L (SD 1.5) and mean CsA-C0 level was 52 ng/mL (SD 23). The GFR of
      transplanted kidneys in children with TN improved by changing immunosuppression
      from CsA/MMF/Pred to everolimus and low-dose CsA.

PMID- 17430486
TI  - Influence of the CYP3A5 genotype on tacrolimus pharmacokinetics and
      pharmacodynamics in young kidney transplant recipients.
AB  - CYP3A enzyme plays a pivotal role in TAC metabolism. The aim of this study was to
      analyze retrospectively the influence of CYP3A5 gene polymorphism on TAC
      pharmacokinetics and pharmacodynamics in 30 teenage kidney transplant recipients.
      TAC dose, trough blood levels, apparent volume of distribution, as well as blood
      pressure and antihypertensive therapy obtained at different post-transplant
      periods, were correlated with the corresponding genotype. Despite a therapeutic
      monitoring strategy, heterozygotes (CYP3A5*1/*3) displayed a lower TAC blood
      concentration compared with homozygotes (CYP3A5*3/*3). Therefore, a two-fold
      increase of the daily TAC dose was required in the heterozygotes to reach the
      desired therapeutic target level. A significant group by time interaction effect
      was present for both variables (repeated measures ANOVA: p = 0.002) meaning a
      significant different pharmacokinetic response in these two cohorts. Mean blood
      pressure was also elevated in CYP3A5*1/*3 recipients despite similar
      antihypertensive treatment. This was parallel with an elevated apparent volume of
      distribution of TAC in this group. Thus, the allele-effect was correlated with
      one of the most common TAC side-effects suggesting a possible influence of CYP3A5
      polymorphism on TAC pharmacodynamics. The authors concluded that a pre-emptive
      CYP3A5 pharmacogenetic screening could contribute to better individualization of
      TAC therapy.

PMID- 17430487
TI  - Unexpectedly high inter- and intrapatient variability of ganciclovir levels in
      children.
AB  - Few studies report Ganciclovir or Valganciclovir levels in children. Single
      center, retrospective study of all available Ganciclovir levels in transplanted
      children. Ganciclovir monitoring was performed as previously described [G. Filler
      (1998); Pediatric Nephrology, 12, 6]. For the normalization of dosing to GFR and
      target trough levels, we assumed first-order kinetics. We analyzed 57 Ganciclovir
      levels in 20 children (mean age 8.6 +/- 5.5 yr) treated with intravenous or oral
      Ganciclovir or oral Valganciclovir. Ganciclovir levels were drawn after IV
      therapy (n = 9), during oral Ganciclovir (n = 5), or during oral Valganciclovir
      (n = 15). Oral bioavailability of Valganciclovir was 42.0 +/- 21.8%. The dose
      normalized intrapatient Valganciclovir variability was 83%. Mean GFR was 92 +/-
      22 mL/min/1.73 m(2). Mean Ganciclovir concentration at last available measurement
      was 0.60 +/- 0.09 mg/L. While target trough Ganciclovir levels have not been
      established, possibly subtherapeutic Ganciclovir levels <0.5 mg/L on recommended
      IV doses were found in eight patients. This subset of patients was significantly
      younger (4.5 +/- 3.1 vs. 11.4 +/- 5.0 yr). Levels <0.5 mg/L were found in 24/57
      instances and 10 patients subsequently had their dose increased. The last
      Valganciclovir dose adjusted to a GFR of 100 mL/min/1.73 m(2) was 842 +/- 323
      mg/m(2)/day. A high proportion of patients had low Ganciclovir levels both on
      intravenous and oral therapy. The oral bioavailability of Valganciclovir was 42%.
      Our data suggest substantial inter- and intrapatient variability of Ganciclovir
      levels after pediatric renal transplantation and may support the need for
      pharmacokinetic monitoring of Ganciclovir and Valganciclovir therapy for the
      prevention and treatment of CMV disease after pediatric transplantation. It is
      currently unclear what target trough level would be most suitable.

PMID- 17430488
TI  - Oral graft vs. host disease in children--treatment with topical tacrolimus
      ointment.
AB  - Oral chronic graft vs. host disease (GVHD) frequently presents in patients with
      sclerotic features of skin GVHD and is often associated with considerable
      limitations of oral food intake and decreased quality of life. Systemic
      tacrolimus is efficacious for prophylaxis and treatment of acute and chronic GVHD
      and topical tacrolimus has shown activity in chronic GVHD skin lesions. We
      therefore initiated a pilot study to investigate the safety and efficacy of
      topical tacrolimus ointment in children with oral GVHD. Six patients suffering
      from oral GVHD (five chronic and one acute) were included in the study.
      Tacrolimus ointment 0.1% was applied twice daily using sterile gauze. The only
      side-effects observed were a slight burning discomfort after the first
      application in one patient and after food intake in another patient. Tacrolimus
      was absorbed systemically in four of six patients. Of six patients, we observed a
      complete response in two, a very good partial response (VGPR) in two, and a PR in
      two patients, respectively. We conclude that topical application of tacrolimus
      ointment holds promise as a safe and efficacious treatment for oral GVHD in
      children. The Food and Drug Administration has recently issued a health advisory
      about a potential cancer risk associated with topical tacrolimus treatment of the
      skin; therefore, its benefits should be weighed against its potential risks and
      diligent long-term follow-up should be carried out especially in children.

PMID- 17430489
TI  - Safety and efficacy of prolonged cytomegalovirus prophylaxis with intravenous
      ganciclovir in pediatric and young adult lung transplant recipients.
AB  - CMV infection causes morbidity and mortality after transplantation. Despite a
      wide range of prevention strategies among pediatric lung transplant programs, the
      optimal duration of prophylactic therapy against CMV infection in pediatric lung
      transplantation is unknown. To assess the feasibility, safety, and short-term
      efficacy of extending intravenous ganciclovir administration from six wk duration
      to 12 wk duration in pediatric lung transplant recipients. An open-label pilot
      study was performed in primary pediatric lung transplant recipients with donor
      and/or recipient CMV seropositivity. Intravenous ganciclovir was given for 12 wk
      post-transplantation. Subjects were tracked for protocol completion. Toxicities
      monitored included renal dysfunction, myelosuppression, gastrointestinal and
      neurological complications, as well as infection related to indwelling catheter
      placement. Serial CMV levels were measured to determine short-term efficacy of
      the intervention. Nine of nine subjects enrolled completed the pilot study.
      Subjects' ages ranged from six to 18 yr. Indications for lung transplantation
      included cystic fibrosis (n = 7), idiopathic pulmonary hypertension (n = 1), and
      complex congenital heart disease with pulmonary hypertension (n = 1). Seven
      subjects underwent deceased donor bilateral lung transplantation and two subjects
      underwent heart-lung transplantation. No subjects had protocol-defined drug
      toxicity. No episodes of neutropenia, thrombocytopenia, or renal toxicity
      occurred. Five subjects had catheter-related infections (three after week 12 of
      ganciclovir). Seven of nine subjects had CMV detected by PCR (four prior to
      ganciclovir completion) with only one subject having a positive viral culture for
      CMV viremia (prior to ganciclovir completion). No subjects had UL-97 mutation for
      ganciclovir resistance detected. The use of prolonged prophylactic administration
      of ganciclovir for 12 wk duration is a feasible, safe, and effective treatment to
      prevent CMV viremia based on viral culture in at risk pediatric lung transplant
      recipients. Further clinical studies are underway to determine optimal CMV
      prevention strategies.

PMID- 17430490
TI  - Reversal of tacrolimus-related hypertrophic cardiomyopathy after conversion to
      rapamycin in a pediatric liver transplant recipient.
AB  - Tacrolimus (Tac)-related hypertrophic cardiomyopathy (HCM) has been reported to
      be an unusual but serious complication affecting pediatric patients after solid
      organ transplantation. Herein, we present a case of young liver transplant
      recipient with Tac-induced HCM, treated by discontinuation of Tac followed by
      conversion to rapamycin (Rap). Our case report points out the potential but
      rather low risk of HCM during Tac immunosuppression in pediatric liver
      transplants and demonstrates that replacement of calcineurin inhibitors with
      mammalian target of Rap (mTOR) inhibitors may be an efficacious therapeutic tool
      to effect regression of established cardiac hypertrophy.

PMID- 17430491
TI  - Bowel obstruction due to diaphragmatic hernia in an elder child after pediatric
      liver transplantation.
AB  - A 10-yr-old boy with end-stage liver cirrhosis due to Wilson's disease received a
      living donor liver transplantation (LDLT) at our institution. The donor was his
      father and the graft was a left lateral segment. The liver transplantation
      procedure and the postoperative course were uneventful. Two months after the
      procedure, he developed a first episode of bowel obstruction that was treated
      with conservative therapy. During a second episode of bowel obstruction, he also
      presented respiratory distress. A plain chest X-ray revealed the presence of
      small intestine loops in the right thoracic cavity and bowel obstruction due to
      diaphragmatic hernia was diagnosed. Repair of the diaphragmatic hernia was
      performed and the patient has been doing well after the surgery. Diaphragmatic
      hernia after LDLT is rare but should be recognized as a possible complication
      when a left lobe or a left lateral segment graft is used.

PMID- 17430492
TI  - Successful cardiac transplantation in Barth syndrome--single-centre experience of
      four patients.
AB  - We describe four patients with Barth syndrome who have undergone successful
      orthotopic heart transplantation. Patients are one, seven, 12.5 and 14.7 yr post
      transplantation. One episode of severe infection occurred. Renal dysfunction and
      coronary allograft vasculopathy do not appear accelerated over non-Barth
      patients. Despite withholding purine synthesis inhibitors, these patients have
      not demonstrated an increased rate of rejection.

PMID- 17430493
TI  - Durable remission following a third allogeneic stem cell transplantation in a
      patient with repeatedly relapsing SAA. The importance of stroma cells for
      sustained engraftment?
AB  - Diagnosis of acquired AATP which finally progressed to SAA was established in an
      eight-yr-old boy. PBSCT from an HLA-identical unrelated donor using high numbers
      of CD34+ selected stem cells was performed and resulted in complete remission for
      almost two yr. However, SAA reoccurred with 100% donor hematopoiesis and was
      reversed by a second CD 34+ selected PBSCT from the same donor. Declining blood
      cell counts after an interval of two yr indicated second relapse. Chimerism
      analysis in PB and BM aspirates revealed a small autologous cell population of 4
      12% and 2-11%, respectively. Finally, a third transplantation with unmanipulated
      BM from the same donor resulted in sustained remission with 100% donor
      hematopoiesis. The patient is in complete remission for more than five yr
      following the third SCT. Late graft failure or late graft rejection known to
      occur after transplantation of highly purified CD34+ cells, or even graft
      exhaustion caused by stromal dysfunction due to the underlying disease
      necessitated a third transplantation. Regardless of the cause of relapse,
      transplantation of unmanipulated BM instead of highly purified PBSCTs led to a
      permanent and stable engraftment in a third attempt after two previous PBSCTs.

PMID- 17430494
TI  - Sirolimus is not always responsible for new-onset proteinuria after conversion
      for chronic allograft nephropathy.
AB  - An eight-yr-old combined liver and kidney transplant recipient for hyperoxaluria
      type I developed significant proteinuria and hypertension after conversion of a
      Tacrolimus, MMF, and corticosteroids-based immunosuppression to Sirolimus, low
      dose Tacrolimus, and corticosteroids six and a half yr after the transplant for
      chronic allograft nephropathy. There was only one class I HLA match and the
      recipient had multiple blood exposures prior to transplantation. The patient was
      treated with combined hemodialysis and peritoneal dialysis while awaiting
      transplantation to reduce the oxalate load. A renal biopsy revealed a de novo
      transplant glomerulopathy that was associated with specific HLA antibodies
      unrelated to the donor (HLA DR 17 and 18). After reintroduction of MMF, these
      antibodies became undetectable and the proteinuria completely resolved. We
      hypothesize that HLA antibodies may cause transplant glomerulopathy even if they
      are not donor-specific. Their production appears more susceptible to MMF therapy.
      A thorough work-up of new-onset proteinuria after conversion to Sirolimus should
      be performed, including an immunological work-up and a renal biopsy.

PMID- 17430495
TI  - Epstein-Barr virus-associated lymphoproliferative disease in oral cavity in a
      renal transplant recipient: a case report.
AB  - A 10-yr-old child on long-term cyclosporin immunosuppression for a renal
      transplant presented with gingival swelling enlargement, in a background of
      gingival hyperplasia. It is tempting to assume that it is a drug-related lesion;
      perhaps, an area of plaque-related inflammation. An incisional biopsy revealed a
      monomorphic B-cell post-transplant lymphoproliferative disease (PTLD). At this
      stage, high Epstein-Barrr virus (EBV) titres supported a diagnosis of EBV-driven
      PTLD. Despite discontinuation of cyclosporin and reduction of EBV viral load to
      undetectable levels, there was considerable enlargement of the tumour. The
      patient underwent six courses of cyclophosphamide, vincristine and prednisolone
      chemotherapy. This resulted in a dramatic reduction in the size of the right
      mandibular mass with complete mucosal healing intra-orally. Her renal transplant
      still has good function and there is no evidence of PTLD recurrence 23 months
      after initial diagnosis. This case illustrates that PTLD can manifest in unusual
      sites and in transplant recipients on cyclosporin immunosuppression it is easy to
      assume that any gingival hyperplasia is drug induced; however, the differential
      diagnosis of gingival hyperplasia should include PTLD.

PMID- 17430499
TI  - Limitations of the human-PBL-SCID mouse model for vaginal transmission of HIV-1.
AB  - PROBLEM: SCID mice reconstituted with human peripheral blood lymphocytes (PBL)
      are amenable to vaginal transmission of HIV-1. We investigated the effectiveness
      of this model to establish systemic HIV-1 infection. METHOD OF STUDY: Eighty
      progesterone-primed C.B-17 SCID mice were reconstituted with human-PBLs and
      intravaginally inoculated with CCR5 HIV-1 (BaL or 92BR09) infected human-PBLs in
      the presence of human semen. After two weeks, viral RNA load in spleen,
      peritoneal lavage (PL), and serum was quantitated by the nucleic acid sequence
      based amplification method. RESULTS: In five independent experiments, spleen from
      8/60 (13.3%), PL from 7/60 (11.6%), and serum from 16/56 (28.5%) mice were
      positive for BaL HIV-1 infection. Similarly, spleen from 4/20 (20%), PL from 1/20
      (5%) and serum from 5/20 (25%) mice vaginally inoculated with 92BR09-infected
      human-PBLs were positive for HIV-1. A one-sided power analysis using normal
      approximation revealed that at 5% significance level, the overall response rate
      need to increase form 0.29 to 0.9 and 80% of the control groups needs to achieve
      a response rate between 6/10 and 9/10 to make the assay feasible. CONCLUSION: The
      incidence of vaginal transmission of CCR5 HIV-1 in the human-PBL-SCID mouse was
      low and variable, which constitutes a major disadvantage for preclinical
      evaluation of vaginal microbicides.

PMID- 17430500
TI  - Association between Chlamydia trachomatis and abnormal uterine bleeding.
AB  - PROBLEM: The purpose was to identify distinct inflammatory markers in endometrial
      tissues of women with abnormal uterine bleeding (AUB) and Chlamydia trachomatis
      infection. METHOD OF STUDY: Archived endometrial specimens from 92 randomly
      selected premenopausal women with AUB were examined for C. trachomatis using the
      species-specific monoclonal antibody against major outer membrane protein (MOMP)
      and for histopathology associated with inflammation. Statistical analyses
      included single and multiple logistic regression. Diagnostic accuracy was
      summarized using receiver operating characteristic (ROC) curves. RESULTS:
      Chlamydia trachomatis was detected in 44 (48%) of 92 AUB specimens. There were
      statistically significant correlations of positive MOMP with higher counts of
      plasma cells (P < 0.01), macrophages (P < 0.0001), and lymphocytic foci (P =
      0.01). The ROC curve for macrophages was the strongest predictor (area under the
      curve = 0.82) for C. trachomatis. CONCLUSION: The prevalence of C. trachomatis in
      women with AUB is under-estimated. Macrophages appear to be a strong marker for
      the presence of C. trachomatis in the endometrium.

PMID- 17430501
TI  - Differential responses of murine vaginal and uterine epithelial cells prior to
      and following herpes simplex virus type 2 (HSV-2) infection.
AB  - PROBLEM: This study was undertaken to evaluate the susceptibility of upper and
      lower reproductive tract epithelial cells (ECs) to herpes simplex virus type 2
      (HSV-2) infection and examine their cytokine secretion patterns prior to and
      following infection. METHOD OF STUDY: Primary EC cultures, grown from murine
      vaginal and uterine tissue, were inoculated with HSV-2. Viral shedding was
      measured in apical and basolateral compartments. Multi-analyte bead-based
      immunoassays run on Luminex, were used to analyse cytokine profiles. RESULTS:
      Both vaginal and uterine ECs became productively infected with HSV-2, ex-vivo.
      Uterine ECs displayed varying degrees of infection, dependent on transepithelial
      resistance of the monolayers. Co-culturing stromal cells did not significantly
      change levels of viral shedding from ECs. Uterine ECs and epithelial-stromal co
      cultures constitutively secreted interleukin (IL)-1alpha, IL-6, mouse homologue
      of human IL-8 (KC) and monocyte chemotactic protein-1 (MCP-1), while vaginal
      epithelial-stromal co-cultures secreted granulocyte-macrophage colony stimulating
      factor (GM-CSF) and KC. Following exposure to HSV-2, IL-6 and MCP-1 levels
      decreased in uterine EC cultures. CONCLUSIONS: This data shows that ECs from the
      upper and lower reproductive tract have different cytokine secretion profiles and
      respond differentially to infection. HSV-2 may be able to suppress epithelial
      cytokine secretion as a strategy to evade host immune system.

PMID- 17430502
TI  - Paediatric intraocular lenses: the power to choose?

PMID- 17430503
TI  - Visual outcome with macular hole surgery.

PMID- 17430504
TI  - Lateral canthal fixation using an oblique vertically orientated asymmetric
      periosteal transposition flap.
AB  - Herein a modification of the highly useful lateral tarsal strip procedure is
      presented. The refinement of the technique uses an oblique, vertically
      orientated, asymmetric, periosteal transposition (OVAPT) flap from the lateral
      orbital rim to fix the tarsal strip. From a consecutive series of 53 patients, A
      cohort of 49 procedures on 41 patients with a minimum of 3-month follow up is
      described. The procedure had a high rate of success in terms of canthal fixation
      over the median 14-month follow up. There was only one case of late stretching of
      the canthal repair in an anophthalmic orbit, one case of recurrent cicatricial
      ectropion due to an inadequate skin graft, and finally a case of early recurrent
      tarsal ectropion. The OVAPT flap further enhances the stability of the tarsal
      strip procedure, and allows greater control of lid position and tension. The pull
      is in a superior and lateral direction, mimicking that of the lateral canthal
      tendon.

PMID- 17430505
TI  - Long-term functional outcome of macular hole surgery correlated to optical
      coherence tomography measurements.
AB  - OBJECTIVE: Evaluation of long-term functional outcome after macular hole surgery
      and its correlation with postoperative optical coherence tomography (OCT).
      METHODS: Before and after surgery a complete clinical examination and OCT were
      performed in 38 patients. Best corrected postoperative visual acuity (VA) was
      correlated to the following OCT parameters: preoperative base and minimum
      diameter of the hole, hole height, hole form factor, retinal thickness and nerve
      fibre layer measurements postoperatively, postoperative foveal contour,
      appearance of retinal pigment epithelium layer and photoreceptor layer. RESULTS:
      Over a mean follow up of 67 months, VA improved significantly (P=0.01). Retinal
      thickness and retinal thickness and nerve-fibre layer measurements of the
      operated eye did not differ from fellow eye. A negative correlation was seen
      between final VA and preoperative base diameter of the hole (r=-0.41, P=0.02) and
      hole height (r=-0.45, P=0.01). The correlation between hole form factor values
      and final VA (r=0.36, P=0.04) was weak. Appearance of the photoreceptor band was
      the only OCT parameter significantly correlating with final VA (r=-0.42, P=0.01)
      and explaining the observed increase (r=-0.32, P=0.05) in VA. CONCLUSION:
      Appearance of the photoreceptor layer on postoperative OCT correlates to
      functional outcome and may help to explain cases of unsatisfactory postoperative
      VA despite successful hole closure.

PMID- 17430506
TI  - Additional gas injection after failed macular hole surgery with internal limiting
      membrane peeling.
AB  - PURPOSE: To report the efficacy of additional intravitreal gas injection in eyes
      where primary failure occurred following apparently successful macular hole
      surgery. METHODS: Patients presenting with macular hole underwent a primary
      surgical procedure consisting of vitrectomy with phacoemulsification and
      intraocular lens implantation. The internal limiting membrane was stained with
      indocyanine green and peeled. At the end of this manoeuvre a fluid-gas exchange
      was performed and the macular hole tamponaded with 20% sulphur hexafluoride. The
      patients were instructed to assume a face-down position for 12 h per day until
      the macular hole closed. In those cases where primary closure was not achieved,
      an additional quantity of 20% sulphur hexafluoride was injected into the vitreous
      cavity via a 27-gauge needle connected to a 5-mL syringe. The patients were
      instructed to assume the same position. RESULTS: A total of 40 eyes from 40
      consecutive patients underwent primary macular hole surgery. The macular hole was
      not successfully closed in seven eyes and a further gas injection was made in
      these eyes. This additional procedure led to macular hole closure in all cases
      within a mean of 4.1 days. Visual acuity improved in all seven eyes, and the
      final visual outcomes were no worse than those eyes that had successful primary
      closure. CONCLUSIONS: Additional gas injection is an effective treatment for eyes
      with open holes following unsuccessful primary surgery.

PMID- 17430507
TI  - Measurement of retinal thickness from three-dimensional images obtained from C
      scan images from the optical coherence tomography ophthalmoscope.
AB  - BACKGROUND: One of the unique features of the optical coherence tomography (OCT)
      ophthalmoscope is that it can record C scan images of the retina. The purpose of
      this study was to determine the best recording time to measure the retinal
      thickness with the OCT ophthalmoscope. In addition, the accuracy of the
      measurements was examined by comparing the values obtained by the OCT
      ophthalmoscope with those obtained with the Stratus OCT Model 3000 (OCT III)
      assuming that the OCT III gives an accurate measurement of retinal thickness.
      METHODS: The topography mode of the OCT ophthalmoscope was used. First, the
      average retinal thickness recorded with 2-s scans was compared with that recorded
      with 4-s scans for a recording area of 15 degreesx15 degrees. Next, the average
      retinal thickness recorded by the OCT ophthalmoscope was compared with that
      obtained by the Fast Macular Thickness program of the OCT III in patients with
      macular oedema. RESULTS: The mean retinal thickness of the central area was 208.1
      microm for both 2 and 4 s recording times. The average retinal thickness obtained
      by the OCT ophthalmoscope was highly correlated and not significantly different
      from the values obtained by the OCT III. The largest differences obtained by the
      two instruments were seen in the parts of the retina with accumulation of hard
      exudates. CONCLUSIONS: Accurate measurements of retinal thickness can be obtained
      with the OCT ophthalmoscope by 2-s scans, and thus, the OCT ophthalmoscope can be
      a valuable instrument for clinical assessments of retinal thickness.

PMID- 17430508
TI  - Alterations of retinal pigment epithelium in central serous chorioretinopathy.
AB  - BACKGROUND: To examine with en face optical coherence tomography (OCT) the
      alterations of retinal pigment epithelium (RPE) in central serous
      chorioretinopathy (CSC) and their role in the pathophysiology of CSC. METHODS: We
      examined retrospectively 30 consecutive eyes of 30 patients with various phases
      of CSC. All patients underwent fluorescein angiography, indocyanine green
      angiography, and en face and longitudinal OCT examinations. RESULTS: Of 25 eyes
      with acute CSC, en face OCT showed RPE abnormalities in 22 eyes (88%) with
      pigment epithelial detachment (PED) in nine eyes (36%) and a small bulge of RPE
      in the posterior pole in 15 eyes (60%). Of four eyes with chronic CSC, OCT showed
      PED in one eye (25%) and a small bulge of RPE in other three eyes (75%). Of 29
      eyes with acute or chronic CSC, fluorescein angiography showed characteristic
      pinpoint leakage in 20 eyes (69%). Of these 20 eyes, a leaking point was located
      within PEDs in five eyes (25%) and was consistent with the bulge of RPE in nine
      eyes (45%). With indocyanine green angiography, 28 (97%) eyes showed choroidal
      vascular hyperpermeability. Ten of the 11 eyes with PED (91%) showed PED within
      the areas of choroidal vascular hyperpermeability. Sixteen of the 18 eyes with a
      bulge of RPE (89%) showed the bulge within areas of choroidal vascular
      hyperpermeability. The one eye in the quiescent CSC exhibited multiple small PEDs
      within the areas of choroidal vascular hyperpermeability by en face OCT.
      CONCLUSIONS: En face OCT enables us to detect alterations of RPE in eyes with
      CSC. Most alterations of RPE were associated with choroidal abnormalities.

PMID- 17430509
TI  - Progression of retinopathy during pregnancy in type 1 diabetes mellitus.
AB  - PURPOSE: The incidence and risk factors for progression of retinopathy during
      pregnancy in women with type 1 diabetes mellitus were retrospectively evaluated.
      METHODS: Fifty-four insulin-dependent diabetic patients at a teaching hospital in
      Saudi Arabia were followed throughout the pregnancy/puerperium with serial
      ophthalmic examination. Dilated fundus examination was performed in each
      trimester and puerperium. RESULTS: Progression of diabetic retinopathy in the
      study occurred in 13/54 (24%) patients--2/22 (9.1%) patients had no diabetic
      retinopathy initially, 4/20 (20%) had non-proliferative diabetic retinopathy
      (NPDR) and 7/12 (58.3%) had proliferative diabetic retinopathy (PDR). Of the
      eight patients with PDR who had no laser treatment before pregnancy, six (75%)
      showed progression but only one of the four patients who had PDR and laser
      treatment prior to pregnancy experienced progression of retinopathy. Eight
      patients in total received panretinal photocoagulation to arrest the progression
      of retinal disease during pregnancy and only one of them had laser treatment
      prior to pregnancy. CONCLUSION: Laser photocoagulation for severe NPDR or early
      PDR prior to pregnancy may protect against rapid progression of PDR. Visual
      impairment resulting from progression of PDR can be prevented by aggressive laser
      treatment during pregnancy. Duration of diabetes>15 years, poor glycaemic control
      and hypertension are high-risk factors in the progression of diabetic retinopathy
      in pregnancy.

PMID- 17430510
TI  - Glaucoma screening: analysis of conventional and telemedicine-friendly devices.
AB  - PURPOSE: Portable, telemedicine-friendly devices offer novel opportunity for
      screening and monitoring glaucoma in the remote and rural regions of the world.
      This study examines the effective combination of telemedicine-friendly screening
      devices for detection of glaucoma in relation with conventional, hospital-based
      devices. METHODS: A total of 399 eyes were screened with telemedicine-friendly
      devices and conventional, hospital-based devices such as ophthalmoscope,
      tonometer and perimeter. RESULTS: Combination of age and family history of
      glaucoma alone has a sensitivity of 35.6% (specificity 94.2%, area under the
      curve 0.81, correctly classified 81.1%) and an addition of telemedicine-friendly
      or conventional visual field tests optimized the sensitivity to 91.1%
      (specificity 93.6%, area under the curve 0.95, correctly classified 93%).
      Analysis indicates good agreement between vertical cup-to-disc ratio by
      ophthalmoscopy and digital image reading. An addition of intraocular pressure
      test does not change sensitivity (35.6%) and specificity (94.2%). CONCLUSION:
      This study indicates that evaluations of cup-to-disc ratio and visual field,
      using telemedicine-friendly devices, are most useful tools in screening for
      glaucoma. When used together these devices may be an alternative for conventional
      glaucoma screenings.

PMID- 17430511
TI  - Paediatric pseudophakia: analysis of intraocular lens power and myopic shift.
AB  - BACKGROUND: At the Alberta Children's Hospital, the authors have been performing
      paediatric cataract extraction with intraocular lens (IOL) implant for over 10
      years. The authors examined the amount of myopic shift that occurs in various age
      groups and cataract types, in order to evaluate the success of predicting the
      appropriate power of IOL to implant. METHODS: This study is a retrospective
      review children undergoing small incision posterior chamber foldable IOL
      implantation between age 1 month and 18 years, from 1995 to 2005. 163 eyes of 126
      patients underwent surgery. All patients were followed for a minimum of 6 months
      postoperatively. The children were divided into four groups at time of surgery:
      Group A: 1-24 months, Group B: 25-48 months, Group C: 49-84 months, Group D: 85
      months-18 years. RESULTS: The mean target refraction for the groups were: Group
      A: +6.37 D, Group B: +4.66 D, Group C: +1.95 D, and Group D: +0.97 D. Children
      under 4 years experienced the most myopic shift and the largest mean rate of
      refractive change per year. Mean change Group A: -5.43 D, Group B: -4.16 D, Group
      C: -1.58 D, Group D: -0.71 D. Eighty-nine per cent of patients with unilateral
      cataracts had a postoperative refraction within 3.00 D of the fellow eye at last
      follow-up visit (mean=3.16 years). CONCLUSIONS: The rate of myopic shift is high
      in children under age 4 years at time of surgery, shifting as much as -12.00 D.
      The mean postoperative target refraction should probably be increased from
      previous literature recommendations. The patient's age at time of cataract
      surgery and the refractive power of fellow eye are all factors to consider when
      deciding what power IOL to surgically implant in a paediatric patient.

PMID- 17430512
TI  - Traumatic intralenticular abscess: a case series.
AB  - PURPOSE: To report the clinical presentation, management and outcome of eyes with
      traumatic intralenticular abscess. METHODS: In this interventional case series,
      records of eight patients (eight eyes) with intralenticular abscess developing
      following trauma were reviewed. All patients underwent extracapsular cataract
      extraction with intracameral antibiotics with or without pars plana vitrectomy.
      Main outcome measures studied were resolution of infection and final visual
      outcome. RESULTS: Lens abscess developed in six eyes following penetrating injury
      and in two eyes following intraocular penetration of caterpillar hair. Gram
      positive cocci were cultured from the lens aspirate in five eyes and
      Staphylococcus epidermidis was the most common organism isolated. Cataract
      extraction resulted in control of the infection in all eyes and seven eyes
      (87.5%) had a favourable visual outcome. CONCLUSION: Early lens extraction with
      intracameral antibiotics in eyes with intralenticular abscess allows control of
      infection with good visual outcome.

PMID- 17430513
TI  - Assisted local anaesthesia for endoscopic dacryocystorhinostomy.
AB  - BACKGROUND: Endoscopic dacryocystorhinostomy is traditionally performed under
      general anaesthesia. However, there are reports in the literature of various
      local anaesthetic techniques with or without sedation for this procedure. An
      effective and acceptable local anaesthetic technique enables the avoidance of the
      risks associated with general anaesthesia, particularly for elderly patients,
      with the added benefit of reduced bleeding, reduced nausea and vomiting, and
      reduced length of hospital stay and thus health care cost savings. This study
      aims to evaluate the safety and patient acceptance of a minimally invasive
      assisted local anaesthetic technique for endoscopic dacryocystorhinostomy.
      METHODS: A prospective questionnaire-based study is presented of 24 consecutive
      adult patients who underwent 26 endoscopic dacryocystorhinostomies in a day
      surgery including 22 primary and four revision procedures performed by one
      surgeon under local anaesthesia and sedation over a 4-month period. RESULTS:
      Apart from persistent postoperative vomiting in one patient there were no
      anaesthetic complications. There were no instances of epistaxis. The mean pain
      score on a visual analogue scale of 0-10 was 1.56 and 56% reported no pain.
      Ninety-two per cent would recommend the procedure to others. CONCLUSION: This
      assisted local anaesthetic technique for endoscopic dacryocystorhinostomy is safe
      and acceptable to patients.

PMID- 17430514
TI  - Blepharophimosis-ptosis-epicanthus inversus syndrome: objective analysis of
      surgical outcome in patients from a single unit.
AB  - BACKGROUND: The aim was to objectively assess surgical outcome in
      blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). METHOD:
      Retrospective review of 14 consecutive patients with BPES. Mustarde double z
      plasty (at about age 4) and autogenous fascia lata Crawford brow suspension (9-12
      months later) were used in all. One consultant performed all operations. Patient
      photographs were scanned and magnified for analysis. Preoperative and
      postoperative intercanthal distance, vertical palpebral aperture and cosmetic
      outcome were measured. Values were converted into ratios. RESULTS: Bilateral
      (mildly asymmetrical) ptosis and symmetrical epicanthic folds were found in all
      preoperatively. Seventy-one per cent had severe folds. Preoperative intercanthal
      distance ratio range was 1.26-1.60 (non-BPES=1.0). Median reduction post surgery
      was 26% (P=0.001, Wilcoxon's signed ranks test). Patients with largest
      preoperative ratio displayed greatest correction (P=0.029). Mustarde technique
      completely abolished all epicanthic folds and unmasked prominent caruncles in
      all. Fifty per cent had mild scarring postoperatively in the medial canthal
      region. Median change in marginal reflex distance ratio (right)=22.2% (P=0.012),
      left=18.2% (P=0.008), Wilcoxon's signed ranks tests. Postoperatively all had
      formed eyelid creases with improved upper lid position symmetry. CONCLUSIONS:
      This is the first known study objectively assessing surgical outcome in BPES.
      Mustarde double z plasty and Crawford autogenous fascia lata brow suspension are
      an effective surgical combination in the treatment of this syndrome, with overall
      cosmetic benefit.

PMID- 17430515
TI  - Comparison of acute structural and histopathological changes of the porcine
      ciliary processes after endoscopic cyclophotocoagulation and transscleral
      cyclophotocoagulation.
AB  - BACKGROUND: The objective of this study is to investigate the acute histological
      effects of transscleral cyclophotocoagulation and endoscopic
      cyclophotocoagulation on the ciliary body and other structures of porcine eyes
      compared with untreated controls. METHODS: Transscleral cyclophotocoagulation and
      endoscopic cyclophotocoagulation were performed on porcine eyes. Detailed
      histological evaluations were performed with light and scanning electron
      microscopy of treated eyes and compared with untreated controls. RESULTS:
      Histological changes were observed with both light and scanning electron
      microscopy for all treated tissues. Tissue treated with transscleral
      cyclophotocoagulation showed pronounced tissue disruption of the ciliary body
      muscle and stroma, ciliary processes, and both pigmented and non-pigmented
      ciliary epithelium. Endoscopic cyclophotocoagulation-treated tissue exhibited
      pronounced contraction of the cilliary processes with disruption of the ciliary
      body epithelium, with less architectural disorginization and sparing of the
      ciliary body muscle. The sclera was not affected by either laser treatment.
      CONCLUSION: The endoscopic cyclophotocoagulation treatment caused less damage to
      the ciliary body compared with the transscleral cyclophotocoagulation when
      evaluated by light and scanning electron microscopy. Compared with transscleral
      cyclophotocoagulation, endoscopic cyclophotocoagulation appears to be a more
      selective form of cyclophotocoagulation resulting in less tissue disruption while
      achieving the goal of destroying ciliary body epithelium.

PMID- 17430516
TI  - Disseminated mucormycosis and orbital ischaemia in combination immunosuppression
      with a tumour necrosis factor alpha inhibitor.
AB  - Disseminated mucormycosis, with pulmonary and cerebral angioinvasive disease,
      developed in a 65-year-old woman with rheumatoid arthritis being treated with
      combination immunosuppression including adalimumab. Clinical presentation
      included progressive orbital ischaemia. To the best of the authors' knowledge,
      this is the first reported case of disseminated mucormycosis in a patient treated
      with a tumour necrosis factor inhibitor. Important pathophysiological factors are
      considered.

PMID- 17430517
TI  - Ludwik Zamenhof: a colleague of rare distinction.
AB  - Ludwik Zamenhof trained as an ophthalmologist in Vienna at the end of the 19th
      century. He is best known as the originator of Esperanto and devoted his life to
      the ideals of secular humanism and ethnic tolerance. Few individuals left a
      nobler legacy, yet in a tragic irony when the Nazis invaded Poland in World War
      Two his family were singled out for persecution.

PMID- 17430522
TI  - In vivo microscopy of Best's Vitelliform Macular Dystrophy: optical coherence
      tomography study of combined stage III and IV lesions.
AB  - A 35-year-old man presented with decreased vision in both eyes. Fundus
      biomicroscopy of the right eye revealed a pseudohypopyon along with an area of
      hyperpigmentation and scarring at the macula (combined stage III and IVb Best's
      Vitelliform Macular Dystrophy [BVMD]). The left eye showed the presence of a
      pseudohypopyon along with macular atrophy (combined stage III and IVa). On
      optical coherence tomography both eyes had a neurosensory retinal detachment with
      an optically clear subretinal zone, an accumulation of material between
      neurosensory retina and the retinal pigment epithelium corresponding to the
      pseudohypopyon and subfoveal photoreceptor atrophy. We document on optical
      coherence tomography the transition of BVMD from stage III to IV (in the form of
      the combined stage). These new findings may be considered unique for this stage
      of BVMD, and would help in a further understanding of the disease as it passes
      through its various stages.

PMID- 17430523
TI  - Leucocytoclastic vasculitis presenting as bilateral marginal keratitis.
AB  - Leucocytoclastic vasculitis is an immune-mediated, neutrophil-induced small
      vessel disease. Clinically, it presents with cutaneous palpable painless purpuric
      papules on the extremities. Ocular manifestation reported in the literature is
      rare and includes peripheral ulcerative keratitis, panuveitis and multifocal
      retinitis all preceded by cutaneous lesions. Herein a fatal case of
      leucocytoclastic vasculitis initially presenting with bilateral marginal
      keratitis without any cutaneous lesions is reported.

PMID- 17430524
TI  - Scleral perforation after trans-scleral cyclodiode laser for intraocular pressure
      reduction.
AB  - Herein a case is reported of a full-thickness scleral burn in the left eye of a
      61-year-old man, following contact trans-scleral cyclodiode laser treatment for
      traumatic aphakic glaucoma, unresponsive to maximal medical treatment. The defect
      was successfully repaired by scleral suturing under local anaesthetic.

PMID- 17430525
TI  - In vivo confocal microscopy and polarizing microscopy of the cornea in a patient
      with nephropathic cystinosis.
AB  - The clinicopathological and in vivo confocal microscopic characteristics of the
      corneas from a patient with infantile cystinosis is reported. Crystals were
      demonstrated in the epithelium and stroma of this patient.

PMID- 17430526
TI  - Culture-proven Aspergillus fumigatus infection in a primary hydroxyapatite
      orbital implant.
AB  - Hydroxyapatite orbital implants are widely used in enucleation surgery. Infection
      in this setting is an uncommon but severe complication. Herein a patient with a 3
      year history of chronic socket discharge, orbital discomfort, conjunctival
      breakdown and implant exposure after enucleation and implantation of a
      hydroxyapatite sphere 7 years previously is reported. Repeated attempts at
      covering the exposed implant failed. Eventually the implant was removed, and
      Aspergillus fumigatus was cultured from the explanted material. This is the
      second reported case of Aspergillus infection of a hydroxyapatite orbital
      implant, and the first case where fungal cultures were positive.

PMID- 17430527
TI  - Effect of povidone-iodine on the contamination of needles and cannula tips used
      in ocular anaesthesia.

PMID- 17430528
TI  - Digital Voice Signature: the future of consent?

PMID- 17430530
TI  - Nursing language in a time of change: capturing the focus of the discipline.

PMID- 17430533
TI  - Improved quality of nursing documentation: results of a nursing diagnoses,
      interventions, and outcomes implementation study.
AB  - PURPOSE: To evaluate the impact of the quality of nursing diagnoses,
      interventions, and outcomes in an acute care hospital following the
      implementation of an educational program. METHOD: In a pretest-posttest
      experimental design study, nurses from 12 wards of a Swiss hospital received an
      educational intervention--an introductory class and consecutive classes, using a
      case discussion method--to implement nursing diagnoses, interventions, and
      outcomes. Two sets of 36 randomly selected nursing records were evaluated before
      and after implementation. The quality of documented nursing diagnoses,
      interventions, and nursing-sensitive patient outcomes was assessed by 29 Likert
      type items with a 0-4 scale instrument, called Quality of Nursing Diagnoses,
      Interventions, and Outcomes (Q-DIO) and tested using t-tests. FINDINGS:
      Significant enhancements in the quality of documented nursing diagnoses,
      interventions, and outcomes were found following the implementation of a planned
      educational program. CONCLUSIONS: The implementation of NANDA, NIC, and NOC (NNN)
      nursing diagnoses, interventions, and outcomes led to higher quality of nursing
      diagnosis documentation, etiology-specific nursing interventions, and nursing
      sensitive patient outcomes. IMPLICATIONS FOR NURSING PRACTICE: Educational
      measures support nurses to improve documentation of diagnoses, interventions, and
      outcomes. The Q-DIO is a useful audit tool.

PMID- 17430534
TI  - Patterns of nursing intervention use across 6 days of acute care hospitalization
      for three older patient populations.
AB  - PURPOSE: The purpose was to (a) identify frequently used nursing interventions,
      and (b) describe patterns of interventions used for each of the three patient
      groups. METHODS: This secondary data analysis used data from an academic medical
      center where the Nursing Interventions Classification (NIC) was used to
      electronically document nursing care. Descriptive statistics describe the types,
      frequencies, and patterns of NIC interventions delivered to three older acute
      care populations. FINDINGS: Four NIC treatments were frequently used in all
      patient groups. There were also NIC treatments and patterns of treatments that
      were unique to each group. CONCLUSIONS AND IMPLICATIONS: Using standardized
      nursing language in electronic medical records (EMRs) enables data extraction and
      analysis. Data extracted from EMRs provides nurse administrators with a tool to
      guide decisions regarding nurse staffing, education, evaluation, and resource
      allocation.

PMID- 17430537
TI  - Nurse practitioners in Canada: beginnings, benefits, and barriers.
AB  - PURPOSE: The goal of this qualitative study was to investigate the experiences of
      nurse practitioners (NPs) 1 year after they were first introduced to a mostly
      rural Canadian province. DATA SOURCES: Qualitative analyses of individual 45-min
      interviews with seven of the nine NPs in the province were carried out.
      CONCLUSIONS: Three main themes of importance were identified. First, a nursing
      philosophy with a holistic approach was described as being clearly different from
      medical care. Second, difficulties and barriers encountered in the establishment
      of the profession in the province were described. Third, despite these barriers,
      a pioneering outlook characterized by a sense of excitement and pride in the work
      was expressed. IMPLICATIONS FOR PRACTICE: For NPs to work effectively to reduce
      healthcare costs and increase access to health care, they need to be accepted by
      both the public and the other healthcare professionals. Moreover, it may be
      difficult for NPs to maintain their philosophy of care in the face of the
      expectations placed upon them.

PMID- 17430538
TI  - Unipolar or bipolar depression? Improving diagnostic confidence with the adult
      patient.
AB  - PURPOSE: The purpose of this article is to inform advanced practice nurses in
      primary care about the differential diagnosis of bipolar disorder (BD), when
      depression is identified in the adult patient. DATA SOURCES: Selected research
      and clinical articles. CONCLUSIONS: Adult patients with BD are much more likely
      to seek treatment for depression than for mania or hypomania. Recognition of BD
      is improved when the primary care clinician is alerted to the factors indicating
      bipolarity and utilizes available screening tools. IMPLICATIONS FOR PRACTICE:
      Misdiagnosis of a bipolar spectrum disorder delays proper treatment and precludes
      adequate management both pharmacologically and psychotherapeutically.

PMID- 17430539
TI  - The patient with Parkinson's disease: part I-treating the motor symptoms; part II
      treating the nonmotor symptoms.
AB  - PURPOSE: This two-part article provides the nurse practitioner (NP) with
      information on the developments in the pathophysiology and expanded treatment
      options in the motor and nonmotor symptoms of Parkinson's disease (PD). The
      discussion provides treatment strategies that may offer improved ability to
      manage the disabling symptoms of this neurodegenerative disorder. DATA SOURCES:
      Review of scientific literature from PubMed search for English language articles
      on PD from 1998 to 2005 and books or chapters in textbooks published on the
      disease in the same time frame provided the data source for this article. The
      content reflects our clinical judgments and experience from clinical practice in
      the Movement Disorder Clinic at Mayo Clinic Arizona. CONCLUSIONS: The high
      prevalence of the disease and important advances in its management means that the
      NP needs to have knowledge of the disorder and the combination of multiple
      treatment options available for both the motor and the nonmotor symptoms.
      IMPLICATIONS FOR PRACTICE: PD is a progressive neurodegenerative disease
      affecting 1% of persons over the age of 60 in the United States. As prevalence
      increases with age, so does the need for early accurate diagnosis and proper
      treatment of the PD by the clinician. Advances in the treatment for the motor and
      nonmotor symptoms of PD provide the clinician with increased options to improve
      the patient's quality of life.

PMID- 17430540
TI  - Barriers to nurse entrepreneurship: a study of the process model of
      entrepreneurship.
AB  - PURPOSE: The potential for nurse entrepreneurship to contribute to the
      effectiveness of healthcare delivery is well acknowledged, yet it has not been
      fully realized. Using the process model of entrepreneurship, we attempted to
      glean information from nursing professionals through focus groups on the barriers
      to starting a business. DATA SOURCES: Two focus groups were used and expert
      moderators conducted these exercises. The first focus group included two hospital
      administrators, a nurse entrepreneur, an ophthalmology entrepreneur, and a dean
      of the nursing school familiar with nurse entrepreneurship. The second focus
      group used 20 students in a nurse practitioner program. CONCLUSIONS: The study
      findings indicate nurse practitioners and other nursing professionals do
      recognize the potential of nurse entrepreneurship. However, several barriers
      prevent them from exploiting the identified opportunity. IMPLICATIONS FOR
      PRACTICE: While the barriers are significant, we believe they can be overcome
      with coordinated action by individual nurses, professional associations, and
      public policy initiatives. Several suggestions are offered to nurses seeking to
      become nurse entrepreneurs.

PMID- 17430541
TI  - X-linked agammaglobulinemia in a 10-year-old child: a case study.
AB  - PURPOSE: To discuss the advanced practice nurse's diagnosis and management of an
      unsuspected primary immunodeficiency (PI) disease, X-linked agammaglobulinemia
      (XLA), in a child. DATA SOURCES: Review of historical and current scientific
      literature, practice guidelines, and a case study. CONCLUSIONS: While a diagnosis
      of XLA is most commonly made in the first 3 years of life, this case study
      presents a 10-year-old boy's circuitous route to this diagnosis. A diagnosis of
      an immune defect should be considered for patients with chronic, recurrent, or
      unusual infections. For patients who lack immune globulins and antibodies,
      intravenous immune globulin, given monthly and continued throughout life, is the
      standard of care. IMPLICATIONS FOR PRACTICE: Diagnosis of children and adults
      with primary immune deficiency diseases may be delayed if practitioners fail to
      find the root cause of recurrent infections. Nurses as patient advocates should
      recognize the need for a referral in clinical cases where immunodeficiency may
      not be suspected. Evaluation of the immune system is performed by a panel of
      blood tests. There is a need to increase awareness of PI, their manifestations,
      and treatment among nurses both at the bedside and in advanced practice settings.

PMID- 17430543
TI  - Antibiotic-prescribing habits of nurse practitioners treating adult patients:
      antibiotic use and guidelines survey adult.

PMID- 17430544
TI  - Emerging trends in the functional genomics of the abiotic stress response in crop
      plants.
AB  - Plants are exposed to different abiotic stresses, such as water deficit, high
      temperature, salinity, cold, heavy metals and mechanical wounding, under field
      conditions. It is estimated that such stress conditions can potentially reduce
      the yield of crop plants by more than 50%. Investigations of the physiological,
      biochemical and molecular aspects of stress tolerance have been conducted to
      unravel the intrinsic mechanisms developed during evolution to mitigate against
      stress by plants. Before the advent of the genomics era, researchers primarily
      used a gene-by-gene approach to decipher the function of the genes involved in
      the abiotic stress response. However, abiotic stress tolerance is a complex trait
      and, although large numbers of genes have been identified to be involved in the
      abiotic stress response, there remain large gaps in our understanding of the
      trait. The availability of the genome sequences of certain important plant
      species has enabled the use of strategies, such as genome-wide expression
      profiling, to identify the genes associated with the stress response, followed by
      the verification of gene function by the analysis of mutants and transgenics.
      Certain components of both abscisic acid-dependent and -independent cascades
      involved in the stress response have already been identified. Information
      originating from the genome-wide analysis of abiotic stress tolerance will help
      to provide an insight into the stress-responsive network(s), and may allow the
      modification of this network to reduce the loss caused by stress and to increase
      agricultural productivity.

PMID- 17430545
TI  - Increasing seed oil content in oil-seed rape (Brassica napus L.) by over
      expression of a yeast glycerol-3-phosphate dehydrogenase under the control of a
      seed-specific promoter.
AB  - Previous attempts to manipulate oil synthesis in plants have mainly concentrated
      on the genes involved in the biosynthesis and use of fatty acids, neglecting the
      possible role of glycerol-3-phosphate supply on the rate of triacylglycerol
      synthesis. In this study, a yeast gene coding for cytosolic glycerol-3-phosphate
      dehydrogenase (gpd1) was expressed in transgenic oil-seed rape under the control
      of the seed-specific napin promoter. It was found that a twofold increase in
      glycerol-3-phosphate dehydrogenase activity led to a three- to fourfold increase
      in the level of glycerol-3-phosphate in developing seeds, resulting in a 40%
      increase in the final lipid content of the seed, with the protein content
      remaining substantially unchanged. This was accompanied by a decrease in the
      glycolytic intermediate dihydroxyacetone phosphate, the direct precursor of
      glycerol-3-phosphate dehydrogenase. The levels of sucrose and various metabolites
      in the pathway from sucrose to fatty acids remained unaltered. The results show
      that glycerol-3-phosphate supply co-limits oil accumulation in developing seeds.
      This has important implications for strategies that aim to increase the overall
      level of oil in commercial oil-seed crops for use as a renewable alternative to
      petrol.

PMID- 17430546
TI  - Intraperitoneal immunization with oligomannose-coated liposome-entrapped soluble
      leishmanial antigen induces antigen-specific T-helper type immune response in
      BALB/c mice through uptake by peritoneal macrophages.
AB  - The present study demonstrates that the intraperitoneal administration of soluble
      leishmanial antigen (SLA) entrapped in liposomes coated with neoglycolipids
      containing oligomannose residues (mannopentaose or mannotriose) strongly induces
      an antigen-specific T-helper type 1 (Th1) immune response in BALB/c mice. In
      response to in vitro stimulation with SLA, spleen cells from mice that had
      received oligomannose-coated liposomes encasing SLA (SLA-OML) displayed greater
      interferon (IFN)-gamma and interleukin (IL)-2 production and lower IL-4 and IL-5
      production than spleen cells from mice that had received SLA alone, indicating
      that the SLA-specific Th1 immune response had predominantly been induced in the
      mice that had received SLA-OML. After subsequent infection with Leishmania major,
      mice that had received SLA-OML were effectively protected against the disease,
      with a predominant production of IFN-gamma. OML were preferentially and rapidly
      incorporated into peritoneal macrophages, and the transplantation of macrophages
      containing SLA-OML into the peritoneal cavity also induced protection against L.
      major infection. Thus, SLA-OML were shown to successfully induce a specific Th1
      immune response capable of controlling L. major infection in BALB/c mice through
      the effective uptake of OML by peritoneal macrophages.

PMID- 17430547
TI  - Early responses associated with chronic pathology in murine schistosomiasis.
AB  - Inbred male CBA/J mice infected with Schistosoma mansoni develop either
      hypersplenomegaly syndrome (HSS) or moderate splenomegaly syndrome (MSS) by 20
      weeks of infection. Pathologically and immunologically, MSS and HSS closely
      parallel the intestinal and hepatosplenic clinical forms of schistosomiasis in
      humans, respectively. By 6 weeks after infection, mice that eventually will
      become MSS develop T cell-stimulatory, cross-reactive idiotypes (CRI) while HSS
      mice never produce CRI. Because presence of CRI is useful to predict degree of
      chronic pathology, we used this measure to investigate what other early
      immunological events occurred in animals destined to develop severe morbidity. At
      8 weeks of infection, there was a strong inverse correlation between CRI and
      splenomegaly, egg counts, and liver hydroxyproline. Similarly, phorbol myristate
      acetate (PMA)- and ionomycin-stimulated intracellular cytokine expression of IL
      4, IL-5, and GM-CSF in splenic CD4(+) T cells was inversely correlated with serum
      CRI and directly correlated with spleen size. In contrast, spleen cell
      intracellular TNF-alpha and peritoneal cell production of nitric oxide
      demonstrated positive correlations with CRI and inverse correlations with
      measures of morbidity. Surprisingly, IL-10 and IFN-gamma were not correlated with
      CRI levels. These studies link chronic pathology to certain immunological
      responses during the acute phase of schistosomiasis.

PMID- 17430549
TI  - Chronic exposure to schistosome eggs reduces serum cholesterol but has no effect
      on atherosclerotic lesion development.
AB  - Previous studies have shown that people infected with schistosomiasis have lower
      levels of serum cholesterol than uninfected controls. To better understand the
      impact of this parasitic infection on serum cholesterol levels and on
      atherosclerotic lesion development induced by hypercholesterolemia,
      apolipoprotein E (ApoE)-deficient mice were chronically exposed to the eggs of
      Schistosoma mansoni over a period of 16 weeks. Total serum cholesterol and low
      density lipoprotein (LDL) were reduced in egg-exposed ApoE-deficient mice fed a
      diet high in cholesterol compared to unexposed controls. However, exposure to
      eggs had no effect on atherosclerotic lesion size or progression in ApoE
      deficient mice. Macrophages isolated from egg-exposed mice had an enhanced
      ability to take up LDL but not acetylated LDL (acLDL). This study suggests that
      schistosome eggs alone may alter serum lipid profiles through enhancing LDL
      uptake by macrophages, but these changes do not ultimately affect atherosclerotic
      lesion development.

PMID- 17430548
TI  - Differential immune regulation of activated T cells between cutaneous and mucosal
      leishmaniasis as a model for pathogenesis.
AB  - Cutaneous (CL) and mucosal leishmaniasis (ML) are characterized by a predominant
      type 1 immune response (IFN-gamma and TNF-alpha production) and strong
      inflammatory response in the lesions with few parasites. This exacerbated type 1
      response is more evident in ML as compared to CL. Our main hypothesis is that a
      differential immune regulation of T cell activation leads to over reactive T
      cells in ML. In the present study, we investigated immunological factors that
      could explain the mechanisms behind it by comparing some immune regulatory
      mechanisms between ML and CL patients: frequency of cells expressing co
      stimulatory molecules, apoptotic markers, T cell activation markers; and ability
      of neutralizing antibodies to IL-2, IL-12 and IL-15 do down-regulate IFN-gamma
      production in leishmania antigen-stimulated peripheral blood mononuclear cells
      (PBMC). Interestingly, in CL anti-IL-2 and anti-IL-15 significantly suppressed
      antigen-specific IFN-gamma production, while in ML only anti-IL-2 suppressed IFN
      gamma production. Finally, higher frequency of CD4+ T cells expressing CD28-,
      CD69+ and CD62L(low) were observed in ML as compared to CL. These data indicate
      that an exacerbated type 1 response in ML is differentially regulated and not
      appropriately down modulated, with increased frequencies of activated effectors T
      cells, maintaining the persistent inflammatory response and tissue damage
      observed in ML.

PMID- 17430550
TI  - Significant differences in GM allotype frequencies between two sympatric tribes
      with markedly differential susceptibility to malaria.
AB  - Fulani and Masaleit, sympatric tribes in eastern Sudan, are characterized by
      marked differences in susceptibility to Plasmodium falciparum malaria. To
      determine whether the two tribes differ in the frequency of immunoglobulin GM/KM
      allotypes, which are associated with immunity to several pathogens, serum samples
      from 50 Fulani and 50 age- and sex-matched Masaleit subjects were allotyped for
      several GM/KM determinants. The distribution of GM phenotypes as a whole, as well
      as a particular combination of KM and GM phenotypes, differed significantly
      between the two tribes (P = 0.03). These data suggest that GM allotypes may
      contribute to the genetic aetiology of malaria.

PMID- 17430552
TI  - 35te Tagung der Pathologen am Oberrhein/35th Meeting of Pathologists of the Upper
      Rhine Region (PATOR) The Institute of Pathology, University Hospital Freiburg,
      Germany. 1 July 2006. Abstracts.

PMID- 17430551
TI  - The pathology of Plasmodium chabaudi infection is not ameliorated by the secreted
      filarial nematode immunomodulatory molecule, ES-62.
AB  - ES-62 is a phosphorylcholine-containing glycoprotein secreted by filarial
      nematodes. This molecule has been shown to reduce the severity of inflammation in
      collagen-induced arthritis (CIA) in mice, a model of rheumatoid arthritis, via
      down-regulation of anti-collagen type 1 immune responses. Malaria parasites
      induce a pro-inflammatory host immune response and many of the symptoms of
      malaria are immune system-mediated. Therefore we have asked whether the
      immunomodulatory properties of ES-62 can down-regulate the severity of malaria
      infection in BALB/c mice infected with Plasmodium chabaudi. We have found that ES
      62 has no significant effect on the course of P. chabaudi parasitaemia, and does
      not significantly affect any of the measures of malaria-induced pathology taken
      throughout infection.

PMID- 17430554
TI  - Significance analysis of microarray transcript levels in time series experiments.
AB  - BACKGROUND: Microarray time series studies are essential to understand the
      dynamics of molecular events. In order to limit the analysis to those genes that
      change expression over time, a first necessary step is to select differentially
      expressed transcripts. A variety of methods have been proposed to this purpose;
      however, these methods are seldom applicable in practice since they require a
      large number of replicates, often available only for a limited number of samples.
      In this data-poor context, we evaluate the performance of three selection
      methods, using synthetic data, over a range of experimental conditions.
      Application to real data is also discussed. RESULTS: Three methods are
      considered, to assess differentially expressed genes in data-poor conditions.
      Method 1 uses a threshold on individual samples based on a model of the
      experimental error. Method 2 calculates the area of the region bounded by the
      time series expression profiles, and considers the gene differentially expressed
      if the area exceeds a threshold based on a model of the experimental error. These
      two methods are compared to Method 3, recently proposed in the literature, which
      exploits splines fit to compare time series profiles. Application of the three
      methods to synthetic data indicates that Method 2 outperforms the other two both
      in Precision and Recall when short time series are analyzed, while Method 3
      outperforms the other two for long time series. CONCLUSION: These results help to
      address the choice of the algorithm to be used in data-poor time series
      expression study, depending on the length of the time series.

PMID- 17430555
TI  - ProCMD: a database and 3D web resource for protein C mutants.
AB  - BACKGROUND: Activated Protein C (ProC) is an anticoagulant plasma serine protease
      which also plays an important role in controlling inflammation and cell
      proliferation. Several mutations of the gene are associated with phenotypic
      functional deficiency of protein C, and with the risk of developing venous
      thrombosis. Structure prediction and computational analysis of the mutants have
      proven to be a valuable aid in understanding the molecular aspects of clinical
      thrombophilia. RESULTS: We have built a specialized relational database and a
      search tool for natural mutants of protein C. It contains 195 entries that
      include 182 missense and 13 stop mutations. A menu driven search engine allows
      the user to retrieve stored information for each variant, that include genetic as
      well as structural data and a multiple alignment highlighting the substituted
      position. Molecular models of variants can be visualized with interactive tools;
      PDB coordinates of the models are also available for further analysis.
      Furthermore, an automatic modelling interface allows the user to generate
      multiple alignments and 3D models of new variants. CONCLUSION: ProCMD is an up-to
      date interactive mutant database that integrates phenotypical descriptions with
      functional and structural data obtained by computational approaches. It will be
      useful in the research and clinical fields to help elucidate the chain of events
      leading from a molecular defect to the related disease. It is available for
      academics at the URL http://www.itb.cnr.it/procmd/.

PMID- 17430556
TI  - On the origin and evolution of biosynthetic pathways: integrating microarray data
      with structure and organization of the Common Pathway genes.
AB  - BACKGROUND: The lysine, threonine, and methionine biosynthetic pathways share the
      three initial enzymatic steps, which are referred to as the Common Pathway (CP).
      In Escherichia coli three different aspartokinases (AKI, AKII, AKIII, the
      products of thrA, metL and lysC, respectively) can perform the first step of the
      CP. Moreover, two of them (AKI and AKII) are bifunctional, carrying also
      homoserine dehydrogenasic activity (hom product). The second step of the CP is
      catalyzed by a single aspartate semialdehyde dehydrogenase (ASDH, the product of
      asd). Thus, in the CP of E. coli while a single copy of ASDH performs the same
      reaction for three different metabolic routes, three different AKs perfom a
      unique step. Why and how such a situation did emerge and maintain? How is it
      correlated to the different regulatory mechanisms acting on these genes? The aim
      of this work was to trace the evolutionary pathway leading to the extant scenario
      in proteobacteria. RESULTS: The analysis of the structure, organization,
      phylogeny, and distribution of ask and hom genes revealed that the presence of
      multiple copies of these genes and their fusion events are restricted to the
      gamma-subdivision of proteobacteria. This allowed us to depict a model to explain
      the evolution of ask and hom according to which the fused genes are the outcome
      of a cascade of gene duplication and fusion events that can be traced in the
      ancestor of gamma-proteobacteria. Moreover, the appearance of fused genes
      paralleled the assembly of operons of different sizes, suggesting a strong
      correlation between the structure and organization of these genes. A statistic
      analysis of microarray data retrieved from experiments carried out on E. coli and
      Pseudomonas aeruginosa was also performed. CONCLUSION: The integration of data
      concerning gene structure, organization, phylogeny, distribution, and microarray
      experiments allowed us to depict a model for the evolution of ask and hom genes
      in proteobacteria and to suggest a biological significance for the extant
      scenario.

PMID- 17430557
TI  - ESTuber db: an online database for Tuber borchii EST sequences.
AB  - BACKGROUND: The ESTuber database (http://www.itb.cnr.it/estuber) includes 3,271
      Tuber borchii expressed sequence tags (EST). The dataset consists of 2,389
      sequences from an in-house prepared cDNA library from truffle vegetative hyphae,
      and 882 sequences downloaded from GenBank and representing four libraries from
      white truffle mycelia and ascocarps at different developmental stages. An
      automated pipeline was prepared to process EST sequences using public software
      integrated by in-house developed Perl scripts. Data were collected in a MySQL
      database, which can be queried via a php-based web interface. RESULTS: Sequences
      included in the ESTuber db were clustered and annotated against three databases:
      the GenBank nr database, the UniProtKB database and a third in-house prepared
      database of fungi genomic sequences. An algorithm was implemented to infer
      statistical classification among Gene Ontology categories from the ontology
      occurrences deduced from the annotation procedure against the UniProtKB database.
      Ontologies were also deduced from the annotation of more than 130,000 EST
      sequences from five filamentous fungi, for intra-species comparison purposes.
      Further analyses were performed on the ESTuber db dataset, including tandem
      repeats search and comparison of the putative protein dataset inferred from the
      EST sequences to the PROSITE database for protein patterns identification. All
      the analyses were performed both on the complete sequence dataset and on the
      contig consensus sequences generated by the EST assembly procedure. CONCLUSION:
      The resulting web site is a resource of data and links related to truffle
      expressed genes. The Sequence Report and Contig Report pages are the web
      interface core structures which, together with the Text search utility and the
      Blast utility, allow easy access to the data stored in the database.

PMID- 17430558
TI  - Statistical analysis of genomic protein family and domain controlled annotations
      for functional investigation of classified gene lists.
AB  - BACKGROUND: The increasing protein family and domain based annotations constitute
      important information to understand protein functions and gain insight into
      relations among their codifying genes. To allow analyzing of gene proteomic
      annotations, we implemented novel modules within GFINDer, a Web system we
      previously developed that dynamically aggregates functional and phenotypic
      annotations of user-uploaded gene lists and allows performing their statistical
      analysis and mining. RESULTS: Exploiting protein information in Pfam and InterPro
      databanks, we developed and added in GFINDer original modules specifically
      devoted to the exploration and analysis of functional signatures of gene protein
      products. They allow annotating numerous user-classified nucleotide sequence
      identifiers with controlled information on related protein families, domains and
      functional sites, classifying them according to such protein annotation
      categories, and statistically analyzing the obtained classifications. In
      particular, when uploaded nucleotide sequence identifiers are subdivided in
      classes, the Statistics Protein Families&Domains module allows estimating
      relevance of Pfam or InterPro controlled annotations for the uploaded genes by
      highlighting protein signatures significantly more represented within user
      defined classes of genes. In addition, the Logistic Regression module allows
      identifying protein functional signatures that better explain the considered gene
      classification. CONCLUSION: Novel GFINDer modules provide genomic protein family
      and domain analyses supporting better functional interpretation of gene classes,
      for instance defined through statistical and clustering analyses of gene
      expression results from microarray experiments. They can hence help understanding
      fundamental biological processes and complex cellular mechanisms influenced by
      protein domain composition, and contribute to unveil new biomedical knowledge
      about the codifying genes.

PMID- 17430559
TI  - Environment specific substitution tables for thermophilic proteins.
AB  - BACKGROUND: Thermophilic organisms are able to live at high temperatures ranging
      from 50 to > 100 degrees C. Their proteins must be sufficiently stable to
      function under these extreme conditions; however, the basis for thermostability
      remains elusive. Subtle differences between thermophilic and mesophilic molecules
      can be found when sequences or structures from homologous proteins are compared,
      but often these differences are family-specific and few general rules have been
      derived. The availability of complete genome sequences has now made it feasible
      to perform a large-scale comparison between mesophilic and thermophilic proteins,
      the latter of which primarily come from archaeal genomes although a few complete
      genomes of thermophilic eubacteria are also available. RESULTS: We compared
      mesophilic proteins with their thermophilic counterparts of archaeal or
      eubacterial origins independently. This was based on the assumption that in these
      two kingdoms, different mechanisms may have been exploited for the adaptation of
      proteins at high temperatures. We derived the environment specific amino acid
      compositions of thermophilic proteins from 10 archaeal and seven eubacterial
      genomes, by aligning a large number of sequences from thermophilic proteins with
      their close mesophilic homologues of known three-dimensional (3D) structure. We
      further analysed environment specific substitutions, which lead from mesophilic
      proteins to either archaeal or eubacterial thermophilic proteins. CONCLUSION: Our
      comparisons were based on homology-based structural predictions for a large
      number of thermophilic proteins. We demonstrated that thermal adaptation in the
      archaeal and eubacterial kingdoms is achieved in different ways. The main
      differences concern the usage of Gln, Ile and positively charged amino acids. In
      particular archaeal organisms appeared to have acquired thermostability by
      substituting non-charged polar amino acids (such as Gln) with Glu and Lys, and
      non-polar amino acids with Ile on the surface of proteins.

PMID- 17430560
TI  - Correlation analysis reveals the emergence of coherence in the gene expression
      dynamics following system perturbation.
AB  - Time course gene expression experiments are a popular means to infer co
      expression. Many methods have been proposed to cluster genes or to build networks
      based on similarity measures of their expression dynamics. In this paper we apply
      a correlation based approach to network reconstruction to three datasets of time
      series gene expression following system perturbation: 1) Conditional, Tamoxifen
      dependent, activation of the cMyc proto-oncogene in rat fibroblast; 2) Genomic
      response to nutrition changes in D. melanogaster; 3) Patterns of gene activity as
      a consequence of ageing occurring over a life-span time series (25y-90y) sampled
      from T-cells of human donors. We show that the three datasets undergo similar
      transitions from an "uncorrelated" regime to a positively or negatively
      correlated one that is symptomatic of a shift from a "ground" or "basal" state to
      a "polarized" state. In addition, we show that a similar transition is conserved
      at the pathway level, and that this information can be used for the construction
      of "meta-networks" where it is possible to assess new relations among
      functionally distant sets of molecular functions.

PMID- 17430561
TI  - Splicy: a web-based tool for the prediction of possible alternative splicing
      events from Affymetrix probeset data.
AB  - BACKGROUND: The Affymetrix technology is nowadays a well-established method for
      the analysis of gene expression profiles in cancer research studies. However,
      changes in gene expression levels are not the only way to link genes and disease.
      The existence of gene isoforms specifically linked with cancer or apoptosis is
      increasingly found in literature. Hence it is of great interest to associate the
      results of a gene expression study with updated evidences on the transcript
      structure and its possible variants. RESULTS: We present here a web-based
      software tool, Splicy, whose primary task is to retrieve data on the mapping of
      Affymetrix probes to single exons of gene transcripts and displaying graphically
      this information projected on the gene physical structure. Starting from a list
      of Affymetrix probesets the program produces a series of graphical displays, each
      relative to a transcript associated with the gene targeted by a given probe. The
      information on the transcript-by-transcript and exon-by-exon mapping of probe
      pairs can be retrieved both graphically and in the form of tab-separated files.
      The mapping of single probes to NCBI RefSeq or EMBL cDNAs is handled by the ISREC
      mapping tables used in the CleanEx Expression Reference Database Project. We
      currently maintain these mappings for most popular human and mouse Affymetrix
      chips, and Splicy can be queried for matches with human and mouse NCBI RefSeq or
      EMBL cDNAs. CONCLUSION: Splicy generates probeset annotations and images
      describing the relation between the single probes and intron/exon structure of
      the target transcript in all its known variants. We think that Splicy will be
      useful for giving to the researcher a clearer picture of the possible transcript
      variants linked with a given gene and an additional view on the interpretation of
      microarray experiment data. Splicy is publicly available and has been realized in
      the framework of a bioinformatics grant from the Italian Cancer Research
      Association.

PMID- 17430562
TI  - SYMBIOmatics: synergies in Medical Informatics and Bioinformatics--exploring
      current scientific literature for emerging topics.
AB  - BACKGROUND: The SYMBIOmatics Specific Support Action (SSA) is "an information
      gathering and dissemination activity" that seeks "to identify synergies between
      the bioinformatics and the medical informatics" domain to improve collaborative
      progress between both domains (ref. to http://www.symbiomatics.org). As part of
      the project experts in both research fields will be identified and approached
      through a survey. To provide input to the survey, the scientific literature was
      analysed to extract topics relevant to both medical informatics and
      bioinformatics. RESULTS: This paper presents results of a systematic analysis of
      the scientific literature from medical informatics research and bioinformatics
      research. In the analysis pairs of words (bigrams) from the leading
      bioinformatics and medical informatics journals have been used as indication of
      existing and emerging technologies and topics over the period 2000-2005
      ("recent") and 1990-1990 ("past"). We identified emerging topics that were
      equally important to bioinformatics and medical informatics in recent years such
      as microarray experiments, ontologies, open source, text mining and support
      vector machines. Emerging topics that evolved only in bioinformatics were system
      biology, protein interaction networks and statistical methods for microarray
      analyses, whereas emerging topics in medical informatics were grid technology and
      tissue microarrays. CONCLUSION: We conclude that although both fields have their
      own specific domains of interest, they share common technological developments
      that tend to be initiated by new developments in biotechnology and computer
      science.

PMID- 17430563
TI  - Biowep: a workflow enactment portal for bioinformatics applications.
AB  - BACKGROUND: The huge amount of biological information, its distribution over the
      Internet and the heterogeneity of available software tools makes the adoption of
      new data integration and analysis network tools a necessity in bioinformatics.
      ICT standards and tools, like Web Services and Workflow Management Systems (WMS),
      can support the creation and deployment of such systems. Many Web Services are
      already available and some WMS have been proposed. They assume that researchers
      know which bioinformatics resources can be reached through a programmatic
      interface and that they are skilled in programming and building workflows.
      Therefore, they are not viable to the majority of unskilled researchers. A portal
      enabling these to take profit from new technologies is still missing. RESULTS: We
      designed biowep, a web based client application that allows for the selection and
      execution of a set of predefined workflows. The system is available on-line.
      Biowep architecture includes a Workflow Manager, a User Interface and a Workflow
      Executor. The task of the Workflow Manager is the creation and annotation of
      workflows. These can be created by using either the Taverna Workbench or BioWMS.
      Enactment of workflows is carried out by FreeFluo for Taverna workflows and by
      BioAgent/Hermes, a mobile agent-based middleware, for BioWMS ones. Main
      workflows' processing steps are annotated on the basis of their input and output,
      elaboration type and application domain by using a classification of
      bioinformatics data and tasks. The interface supports users authentication and
      profiling. Workflows can be selected on the basis of users' profiles and can be
      searched through their annotations. Results can be saved. CONCLUSION: We
      developed a web system that support the selection and execution of predefined
      workflows, thus simplifying access for all researchers. The implementation of Web
      Services allowing specialized software to interact with an exhaustive set of
      biomedical databases and analysis software and the creation of effective
      workflows can significantly improve automation of in-silico analysis. Biowep is
      available for interested researchers as a reference portal. They are invited to
      submit their workflows to the workflow repository. Biowep is further being
      developed in the sphere of the Laboratory of Interdisciplinary Technologies in
      Bioinformatics - LITBIO.

PMID- 17430564
TI  - BioWMS: a web-based Workflow Management System for bioinformatics.
AB  - BACKGROUND: An in-silico experiment can be naturally specified as a workflow of
      activities implementing, in a standardized environment, the process of data and
      control analysis. A workflow has the advantage to be reproducible, traceable and
      compositional by reusing other workflows. In order to support the daily work of a
      bioscientist, several Workflow Management Systems (WMSs) have been proposed in
      bioinformatics. Generally, these systems centralize the workflow enactment and do
      not exploit standard process definition languages to describe, in order to be
      reusable, workflows. While almost all WMSs require heavy stand-alone applications
      to specify new workflows, only few of them provide a web-based process definition
      tool. RESULTS: We have developed BioWMS, a Workflow Management System that
      supports, through a web-based interface, the definition, the execution and the
      results management of an in-silico experiment. BioWMS has been implemented over
      an agent-based middleware. It dynamically generates, from a user workflow
      specification, a domain-specific, agent-based workflow engine. Our approach
      exploits the proactiveness and mobility of the agent-based technology to embed,
      inside agents behaviour, the application domain features. Agents are workflow
      executors and the resulting workflow engine is a multiagent system - a
      distributed, concurrent system--typically open, flexible, and adaptative. A demo
      is available at http://litbio.unicam.it:8080/biowms. CONCLUSION: BioWMS,
      supported by Hermes mobile computing middleware, guarantees the flexibility,
      scalability and fault tolerance required to a workflow enactment over distributed
      and heterogeneous environment. BioWMS is funded by the FIRB project LITBIO
      (Laboratory for Interdisciplinary Technologies in Bioinformatics).

PMID- 17430565
TI  - p53FamTaG: a database resource of human p53, p63 and p73 direct target genes
      combining in silico prediction and microarray data.
AB  - BACKGROUND: The p53 gene family consists of the three genes p53, p63 and p73,
      which have polyhedral non-overlapping functions in pivotal cellular processes
      such as DNA synthesis and repair, growth arrest, apoptosis, genome stability,
      angiogenesis, development and differentiation. These genes encode sequence
      specific nuclear transcription factors that recognise the same responsive element
      (RE) in their target genes. Their inactivation or aberrant expression may
      determine tumour progression or developmental disease. The discovery of several
      protein isoforms with antagonistic roles, which are produced by the expression of
      different promoters and alternative splicing, widened the complexity of the
      scenario of the transcriptional network of the p53 family members. Therefore, the
      identification of the genes transactivated by p53 family members is crucial to
      understand the specific role for each gene in cell cycle regulation. We have
      combined a genome-wide computational search of p53 family REs and microarray
      analysis to identify new direct target genes. The huge amount of biological data
      produced has generated a critical need for bioinformatic tools able to manage and
      integrate such data and facilitate their retrieval and analysis. DESCRIPTION: We
      have developed the p53FamTaG database (p53 FAMily TArget Genes), a modular
      relational database, which contains p53 family direct target genes selected in
      the human genome searching for the presence of the REs and the expression profile
      of these target genes obtained by microarray experiments. p53FamTaG database also
      contains annotations of publicly available databases and links to other
      experimental data. The genome-wide computational search of the REs was performed
      using PatSearch, a pattern-matching program implemented in the DNAfan tool. These
      data were integrated with the microarray results we produced from the
      overexpression of different isoforms of p53, p63 and p73 stably transfected in
      isogenic cell lines, allowing the comparative study of the transcriptional
      activity of all the proteins in the same cellular background.p53FamTaG database
      is available free at http://www2.ba.itb.cnr.it/p53FamTaG/ CONCLUSION: p53FamTaG
      represents a unique integrated resource of human direct p53 family target genes
      that is extensively annotated and provides the users with an efficient
      query/retrieval system which displays the results of our microarray experiments
      and allows the export of RE sequences. The database was developed for supporting
      and integrating high-throughput in silico and experimental analyses and
      represents an important reference source of knowledge for research groups
      involved in the field of oncogenesis, apoptosis and cell cycle regulation.

PMID- 17430566
TI  - The genopolis microarray database.
AB  - BACKGROUND: Gene expression databases are key resources for microarray data
      management and analysis and the importance of a proper annotation of their
      content is well understood. Public repositories as well as microarray database
      systems that can be implemented by single laboratories exist. However, there is
      not yet a tool that can easily support a collaborative environment where
      different users with different rights of access to data can interact to define a
      common highly coherent content. The scope of the Genopolis database is to provide
      a resource that allows different groups performing microarray experiments related
      to a common subject to create a common coherent knowledge base and to analyse it.
      The Genopolis database has been implemented as a dedicated system for the
      scientific community studying dendritic and macrophage cells functions and host
      parasite interactions. RESULTS: The Genopolis Database system allows the
      community to build an object based MIAME compliant annotation of their
      experiments and to store images, raw and processed data from the Affymetrix
      GeneChip platform. It supports dynamical definition of controlled vocabularies
      and provides automated and supervised steps to control the coherence of data and
      annotations. It allows a precise control of the visibility of the database
      content to different sub groups in the community and facilitates exports of its
      content to public repositories. It provides an interactive users interface for
      data analysis: this allows users to visualize data matrices based on functional
      lists and sample characterization, and to navigate to other data matrices defined
      by similarity of expression values as well as functional characterizations of
      genes involved. A collaborative environment is also provided for the definition
      and sharing of functional annotation by users. CONCLUSION: The Genopolis Database
      supports a community in building a common coherent knowledge base and analyse it.
      This fills a gap between a local database and a public repository, where the
      development of a common coherent annotation is important. In its current
      implementation, it provides a uniform coherently annotated dataset on dendritic
      cells and macrophage differentiation.

PMID- 17430567
TI  - Data handling strategies for high throughput pyrosequencers.
AB  - BACKGROUND: New high throughput pyrosequencers such as the 454 Life Sciences GS
      20 are capable of massively parallelizing DNA sequencing providing an
      unprecedented rate of output data as well as potentially reducing costs. However,
      these new pyrosequencers bear a different error profile and provide shorter reads
      than those of a more traditional Sanger sequencer. These facts pose new
      challenges regarding how the data are handled and analyzed, in addition, the
      steep increase in the sequencers throughput calls for much computation power at a
      low cost. RESULTS: To address these challenges, we created an automated multi
      step computation pipeline integrated with a database storage system. This allowed
      us to store, handle, index and search (1) the output data from the GS20 sequencer
      (2) analysis projects, possibly multiple on every dataset (3) final results of
      analysis computations (4) intermediate results of computations (these allow hand
      made comparisons and hence further searches by the biologists). Repeatability of
      computations was also a requirement. In order to access the needed computation
      power, we ported the pipeline to the European Grid: a large community of
      clusters, load balanced as a whole. In order to better achieve this Grid port we
      created Vnas: an innovative Grid job submission, virtual sandbox manager and job
      callback framework. After some runs of the pipeline aimed at tuning the
      parameters and thresholds for optimal results, we successfully analyzed 273
      sequenced amplicons from a cancerous human sample and correctly found punctual
      mutations confirmed by either Sanger resequencing or NCBI dbSNP. The sequencing
      was performed with our 454 Life Sciences GS 20 pyrosequencer. CONCLUSION: We
      handled the steep increase in throughput from the new pyrosequencer by building
      an automated computation pipeline associated with database storage, and by
      leveraging the computing power of the European Grid. The Grid platform offers a
      very cost effective choice for uneven workloads, typical in many scientific
      research fields, provided its peculiarities can be accepted (these are
      discussed). The mentioned infrastructure was used to analyze human amplicons for
      mutations. More analyses will be performed in the future.

PMID- 17430568
TI  - A global gene evolution analysis on Vibrionaceae family using phylogenetic
      profile.
AB  - BACKGROUND: Vibrionaceae represent a significant portion of the cultivable
      heterotrophic sea bacteria; they strongly affect nutrient cycling and some
      species are devastating pathogens. In this work we propose an improved
      phylogenetic profile analysis on 14 Vibrionaceae genomes, to study the evolution
      of this family on the basis of gene content. The phylogenetic profile is based on
      the observation that genes involved in the same process (e.g. metabolic pathway
      or structural complex) tend to be concurrently present or absent within different
      genomes. This allows the prediction of hypothetical functions on the basis of a
      shared phylogenetic profiles. Moreover this approach is useful to identify
      putative laterally transferred elements on the basis of their presence on
      distantly phylogenetically related bacteria. RESULTS: Vibrionaceae ORFs were
      aligned against all the available bacterial proteomes. Phylogenetic profile is
      defined as an array of distances, based on aminoacid substitution matrixes, from
      single genes to all their orthologues. Final phylogenetic profiles, derived from
      non-redundant list of all ORFs, was defined as the median of all the profiles
      belonging to the cluster. The resulting phylogenetic profiles matrix contains
      gene clusters on the rows and organisms on the columns. Cluster analysis
      identified groups of "core genes" with a widespread high similarity across all
      the organisms and several clusters that contain genes homologous only to a
      limited set of organisms. On each of these clusters, COG class enrichment has
      been calculated. The analysis reveals that clusters of core genes have the
      highest number of enriched classes, while the others are enriched just for few of
      them like DNA replication, recombination and repair. CONCLUSION: We found that
      mobile elements have heterogeneous profiles not only across the entire set of
      organisms, but also within Vibrionaceae; this confirms their great influence on
      bacteria evolution even inside the same family. Furthermore, several hypothetical
      proteins highly correlate with mobile elements profiles suggesting a possible
      horizontal transfer mechanism for the evolution of these genes. Finally, we
      suggested the putative role of some ORFs having an unknown function on the basis
      of their phylogenetic profile similarity to well characterized genes.

PMID- 17430569
TI  - Local comparison of protein structures highlights cases of convergent evolution
      in analogous functional sites.
AB  - BACKGROUND: We performed an exhaustive search for local structural similarities
      in an ensemble of non-redundant protein functional sites. With the purpose of
      finding new examples of convergent evolution, we selected only those matching
      sites composed of structural regions whose residue order is inverted in the
      relative protein sequences. RESULTS: A novel case of local analogy was detected
      between members of the ABC transporter and of the HprK/P families in their ATP
      binding site. This case cannot be derived by events of circular permutation since
      the residues of one of the region pairs are located in reverse order in the
      sequence of the two protein families. One of the analogous binding sites, the one
      identified in HprK/P, is known to also bind pyrophosphate, which is used as
      preferred energy source in its kinase and phosphorylase activity. CONCLUSION: The
      discovery of this striking molecular similarity, also associated to a functional
      similarity, may help in suggesting new experiments aimed at a deeper
      understanding of members of the ABC transporter family known to be involved in
      many serious human diseases.

PMID- 17430570
TI  - A computational approach for detecting peptidases and their specific inhibitors
      at the genome level.
AB  - BACKGROUND: Peptidases are proteolytic enzymes responsible for fundamental
      cellular activities in all organisms. Apparently about 2-5% of the genes encode
      for peptidases, irrespectively of the organism source. The basic peptidase
      function is "protein digestion" and this can be potentially dangerous in living
      organisms when it is not strictly controlled by specific inhibitors. In genome
      annotation a basic question is to predict gene function. Here we describe a
      computational approach that can filter peptidases and their inhibitors out of a
      given proteome. Furthermore and as an added value to MEROPS, a specific database
      for peptidases already available in the public domain, our method can predict
      whether a pair of peptidase/inhibitor can interact, eventually listing all
      possible predicted ligands (peptidases and/or inhibitors). RESULTS: We show that
      by adopting a decision-tree approach the accuracy of PROSITE and HMMER in
      detecting separately the four major peptidase types (Serine, Aspartic, Cysteine
      and Metallo- Peptidase) and their inhibitors among a non redundant set of
      globular proteins can be improved by some percentage points with respect to that
      obtained with each method separately. More importantly, our method can then
      predict pairs of peptidases and interacting inhibitors, scoring a joint global
      accuracy of 99% with coverage for the positive cases (peptidase/inhibitor) close
      to 100% and a correlation coefficient of 0.91%. In this task the decision-tree
      approach outperforms the single methods. CONCLUSION: The decision-tree can
      reliably classify protein sequences as peptidases or inhibitors, belonging to a
      certain class, and can provide a comprehensive list of possible interacting pairs
      of peptidase/inhibitor. This information can help the design of experiments to
      detect interacting peptidase/inhibitor complexes and can speed up the selection
      of possible interacting candidates, without searching for them separately and
      manually combining the obtained results. A web server specifically developed for
      annotating peptidases and their inhibitors (HIPPIE) is available at
      http://gpcr.biocomp.unibo.it/cgi/predictors/hippie/pred_hippie.cgi.

PMID- 17430571
TI  - ProtNet: a tool for stochastic simulations of protein interaction networks
      dynamics.
AB  - BACKGROUND: Protein interactions support cell organization and mediate its
      response to any specific stimulus. Recent technological advances have produced
      large data-sets that aim at describing the cell interactome. These data are
      usually presented as graphs where proteins (nodes) are linked by edges to their
      experimentally determined partners. This representation reveals that protein
      protein interaction (PPI) networks, like other kinds of complex networks, are not
      randomly organized and display properties that are typical of "hierarchical"
      networks, combining modularity and local clustering to scale free topology.
      However informative, this representation is static and provides no clue about the
      dynamic nature of protein interactions inside the cell. RESULTS: To fill this
      methodological gap, we designed and implemented a computer model that captures
      the discrete and stochastic nature of protein interactions. In ProtNet, our
      simplified model, the intracellular space is mapped onto either a two-dimensional
      or a three-dimensional lattice with each lattice site having a linear size (5 nm)
      comparable to the diameter of an average globular protein. The protein filled
      lattice has an occupancy (e.g. 20%) compatible with the estimated crowding of
      proteins in the cell cytoplasm. Proteins or protein complexes are free to
      translate and rotate on the lattice that represents a sort of naive unstructured
      cell (devoid of compartments). At each time step, molecular entities (proteins or
      complexes) that happen to be in neighboring cells may interact and form larger
      complexes or dissociate depending on the interaction rules defined in an
      experimental protein interaction network. This whole procedure can be seen as a
      sort of "discrete molecular dynamics" applied to interacting proteins in a cell.
      We have tested our model by performing different simulations using as interaction
      rules those derived from an experimental interactome of Saccharomyces cerevisiae
      (1378 nodes, 2491 edges) and we have compared the dynamics of complex formation
      in a two and a three dimensional lattice model. CONCLUSION: ProtNet is a cellular
      automaton model, where each protein molecule or complex is explicitly represented
      and where simple interaction rules are applied to populations of discrete
      particles. This tool can be used to simulate the dynamics of protein interactions
      in the cell.

PMID- 17430572
TI  - Cross platform microarray analysis for robust identification of differentially
      expressed genes.
AB  - BACKGROUND: Microarrays have been widely used for the analysis of gene expression
      and several commercial platforms are available. The combined use of multiple
      platforms can overcome the inherent biases of each approach, and may represent an
      alternative that is complementary to RT-PCR for identification of the more robust
      changes in gene expression profiles. In this paper, we combined statistical and
      functional analysis for the cross platform validation of two oligonucleotide
      based technologies, Affymetrix (AFFX) and Applied Biosystems (ABI), and for the
      identification of differentially expressed genes. RESULTS: In this study, we
      analysed differentially expressed genes after treatment of an ovarian carcinoma
      cell line with a cell cycle inhibitor. Treated versus control RNA was analysed
      for expression of 16425 genes represented on both platforms. We assessed
      reproducibility between replicates for each platform using CAT plots, and we
      found it high for both, with better scores for AFFX. We then applied integrative
      correlation analysis to assess reproducibility of gene expression patterns across
      studies, bypassing the need for normalizing expression measurements across
      platforms. We identified 930 genes as differentially expressed on AFFX and 908 on
      ABI, with approximately 80% common to both platforms. Despite the different
      absolute values, the range of intensities of the differentially expressed genes
      detected by each platform was similar. ABI showed a slightly higher dynamic range
      in FC values, which might be associated with its detection system. 62/66 genes
      identified as differentially expressed by Microarray were confirmed by RT-PCR.
      CONCLUSION: In this study we present a cross-platform validation of two
      oligonucleotide-based technologies, AFFX and ABI. We found good reproducibility
      between replicates, and showed that both platforms can be used to select
      differentially expressed genes with substantial agreement. Pathway analysis of
      the affected functions identified themes well in agreement with those expected
      for a cell cycle inhibitor, suggesting that this procedure is appropriate to
      facilitate the identification of biologically relevant signatures associated with
      compound treatment. The high rate of confirmation found for both common and
      platform-specific genes suggests that the combination of platforms may overcome
      biases related to probe design and technical features, thereby accelerating the
      identification of trustworthy differentially expressed genes.

PMID- 17430573
TI  - The MEPS server for identifying protein conformational epitopes.
AB  - BACKGROUND: One of the most interesting problems in molecular immunology is
      epitope mapping, i.e. the identification of the regions of interaction between an
      antigen and an antibody. The solution to this problem, even if approximate, would
      help in designing experiments to precisely map the residues involved in the
      interaction and could be instrumental both in designing peptides able to mimic
      the interacting surface of the antigen and in understanding where immunologically
      important regions are located in its three-dimensional structure. From an
      experimental point of view, both genetically encoded and chemically synthesised
      peptide libraries can be used to identify sequences recognized by a given
      antibody. The problem then arises of which region of a folded protein the
      selected peptides correspond to. RESULTS: We have developed a method able to find
      the surface region of a protein that can be effectively mimicked by a peptide,
      given the structure of the protein and the maximum number of side chains deemed
      to be required for recognition. The method is implemented as a publicly available
      server. It can also find and report all peptide sequences of a specified length
      that can mimic the surface of a given protein and store them in a database. The
      immediate application of the server is the mapping of antibody epitopes, however
      the system is sufficiently flexible for allowing other questions to be asked, for
      example one can compare the peptides representing the surface of two proteins
      known to interact with the same macromolecule to find which is the most likely
      interacting region. CONCLUSION: We believe that the MEPS server, available at
      http://www.caspur.it/meps, will be a useful tool for immunologists and structural
      and computational biologists. We plan to use it ourselves to implement a database
      of "surface mimicking peptides" for all proteins of known structure and proteins
      that can be reliably modelled by comparative modelling.

PMID- 17430574
TI  - A Grid-based solution for management and analysis of microarrays in distributed
      experiments.
AB  - Several systems have been presented in the last years in order to manage the
      complexity of large microarray experiments. Although good results have been
      achieved, most systems tend to lack in one or more fields. A Grid based approach
      may provide a shared, standardized and reliable solution for storage and analysis
      of biological data, in order to maximize the results of experimental efforts. A
      Grid framework has been therefore adopted due to the necessity of remotely
      accessing large amounts of distributed data as well as to scale computational
      performances for terabyte datasets. Two different biological studies have been
      planned in order to highlight the benefits that can emerge from our Grid based
      platform. The described environment relies on storage services and computational
      services provided by the gLite Grid middleware. The Grid environment is also able
      to exploit the added value of metadata in order to let users better classify and
      search experiments. A state-of-art Grid portal has been implemented in order to
      hide the complexity of framework from end users and to make them able to easily
      access available services and data. The functional architecture of the portal is
      described. As a first test of the system performances, a gene expression analysis
      has been performed on a dataset of Affymetrix GeneChip Rat Expression Array
      RAE230A, from the ArrayExpress database. The sequence of analysis includes three
      steps: (i) group opening and image set uploading, (ii) normalization, and (iii)
      model based gene expression (based on PM/MM difference model). Two different
      Linux versions (sequential and parallel) of the dChip software have been
      developed to implement the analysis and have been tested on a cluster. From
      results, it emerges that the parallelization of the analysis process and the
      execution of parallel jobs on distributed computational resources actually
      improve the performances. Moreover, the Grid environment have been tested both
      against the possibility of uploading and accessing distributed datasets through
      the Grid middleware and against its ability in managing the execution of jobs on
      distributed computational resources. Results from the Grid test will be discussed
      in a further paper.

PMID- 17430575
TI  - The BioPrompt-box: an ontology-based clustering tool for searching in biological
      databases.
AB  - BACKGROUND: High-throughput molecular biology provides new data at an incredible
      rate, so that the increase in the size of biological databanks is enormous and
      very rapid. This scenario generates severe problems not only at indexing time,
      where suitable algorithmic techniques for data indexing and retrieval are
      required, but also at query time, since a user query may produce such a large set
      of results that their browsing and "understanding" becomes humanly impractical.
      This problem is well known to the Web community, where a new generation of Web
      search engines is being developed, like Vivisimo. These tools organize on-the-fly
      the results of a user query in a hierarchy of labeled folders that ease their
      browsing and knowledge extraction. We investigate this approach on biological
      data, and propose the so called The BioPrompt-boxsoftware system which deploys
      ontology-driven clustering strategies for making the searching process of
      biologists more efficient and effective. RESULTS: The BioPrompt-box (Bpb) defines
      a document as a biological sequence plus its associated meta-data taken from the
      underneath databank--like references to ontologies or to external databanks, and
      plain texts as comments of researchers and (title, abstracts or even body of)
      papers. Bpboffers several tools to customize the search and the clustering
      process over its indexed documents. The user can search a set of keywords within
      a specific field of the document schema, or can execute Blastto find documents
      relative to homologue sequences. In both cases the search task returns a set of
      documents (hits) which constitute the answer to the user query. Since the number
      of hits may be large, Bpbclusters them into groups of homogenous content,
      organized as a hierarchy of labeled clusters. The user can actually choose among
      several ontology-based hierarchical clustering strategies, each offering a
      different "view" of the returned hits. Bpbcomputes these views by exploiting the
      meta-data present within the retrieved documents such as the references to Gene
      Ontology, the taxonomy lineage, the organism and the keywords. Of course, the
      approach is flexible enough to leave room for future additions of other meta
      information. The ultimate goal of the clustering process is to provide the user
      with several different readings of the (maybe numerous) query results and show
      possible hidden correlations among them, thus improving their browsing and
      understanding. CONCLUSION: Bpb is a powerful search engine that makes it very
      easy to perform complex queries over the indexed databanks (currently only
      UNIPROT is considered). The ontology-based clustering approach is efficient and
      effective, and could thus be applied successfully to larger databanks, like
      GenBank or EMBL.

PMID- 17430576
TI  - Gene models from ESTs (GeneModelEST): an application on the Solanum lycopersicum
      genome.
AB  - BACKGROUND: The structure annotation of a genome is based either on ab initio
      methodologies or on similaritiy searches versus molecules that have been already
      annotated. Ab initio gene predictions in a genome are based on a priori knowledge
      of species-specific features of genes. The training of ab initio gene finders is
      based on the definition of a data-set of gene models. To accomplish this task the
      common approach is to align species-specific full length cDNA and EST sequences
      along the genomic sequences in order to define exon/intron structure of mRNA
      coding genes. RESULTS: GeneModelEST is the software here proposed for defining a
      data-set of candidate gene models using exclusively evidence derived from
      cDNA/EST sequences.GeneModelEST requires the genome coordinates of the spliced
      alignments of ESTs and of contigs (tentative consensus sequences) generated by an
      EST clustering/assembling procedure to be formatted in a General Feature Format
      (GFF) standard file. Moreover, the alignments of the contigs versus a protein
      database are required as an NCBI BLAST formatted report file. The GeneModelEST
      analysis aims to i) evaluate each exon as defined from contig spliced alignments
      onto the genome sequence; ii) classify the contigs according to quality levels in
      order to select candidate gene models; iii) assign to the candidate gene models
      preliminary functional annotations. We discuss the application of the proposed
      methodology to build a data-set of gene models of Solanum lycopersicum, whose
      genome sequencing is an ongoing effort by the International Tomato Genome
      Sequencing Consortium. CONCLUSION: The contig classification procedure used by
      GeneModelEST supports the detection of candidate gene models, the identification
      of potential alternative transcripts and it is useful to filter out ambiguous
      information. An automated procedure, such as the one proposed here, is
      fundamental to support large scale analysis in order to provide species-specific
      gene models, that could be useful as a training data-set for ab initio gene
      finders and/or as a reference gene list for a human curated annotation.

PMID- 17430577
TI  - Prognostic utility of RIFLE for acute renal failure in patients with sepsis.

PMID- 17430578
TI  - Ancient papillomavirus-host co-speciation in Felidae.
AB  - BACKGROUND: Estimating evolutionary rates for slowly evolving viruses such as
      papillomaviruses (PVs) is not possible using fossil calibrations directly or
      sequences sampled over a time-scale of decades. An ability to correlate their
      divergence with a host species, however, can provide a means to estimate
      evolutionary rates for these viruses accurately. To determine whether such an
      approach is feasible, we sequenced complete feline PV genomes, previously
      available only for the domestic cat (Felis domesticus, FdPV1), from four
      additional, globally distributed feline species: Lynx rufus PV type 1, Puma
      concolor PV type 1, Panthera leo persica PV type 1, and Uncia uncia PV type 1.
      RESULTS: The feline PVs all belong to the Lambdapapillomavirus genus, and contain
      an unusual second noncoding region between the early and late protein region,
      which is only present in members of this genus. Our maximum likelihood and
      Bayesian phylogenetic analyses demonstrate that the evolutionary relationships
      between feline PVs perfectly mirror those of their feline hosts, despite a
      complex and dynamic phylogeographic history. By applying host species divergence
      times, we provide the first precise estimates for the rate of evolution for each
      PV gene, with an overall evolutionary rate of 1.95 x 10(-8) (95% confidence
      interval 1.32 x 10(-8) to 2.47 x 10(-8)) nucleotide substitutions per site per
      year for the viral coding genome. CONCLUSION: Our work provides evidence for long
      term virus-host co-speciation of feline PVs, indicating that viral diversity in
      slowly evolving viruses can be used to investigate host species evolution. These
      findings, however, should not be extrapolated to other viral lineages without
      prior confirmation of virus-host co-divergence.

PMID- 17430579
TI  - Mapping of possible prion protein self-interaction domains using peptide arrays.
AB  - BACKGROUND: The common event in transmissible spongiform encephalopathies (TSEs)
      or prion diseases is the conversion of host-encoded protease sensitive cellular
      prion protein (PrPC) into strain dependent isoforms of scrapie associated
      protease resistant isoform (PrPSc) of prion protein (PrP). These processes are
      determined by similarities as well as strain dependent variations in the PrP
      structure. Selective self-interaction between PrP molecules is the most probable
      basis for initiation of these processes, potentially influenced by chaperone
      molecules, however the mechanisms behind these processes are far from understood.
      We previously determined that polymorphisms do not affect initial PrPC to PrPSc
      binding but rather modulate a subsequent step in the conversion process.
      Determining possible sites of self-interaction could elucidate which amino
      acid(s) or amino acid sequences contribute to binding and further conversion into
      other isoforms. To this end, ovine - and bovine PrP peptide-arrays consisting of
      15-mer overlapping peptides were probed with recombinant sheep PrPC fused to
      maltose binding protein (MBP-PrP). RESULTS: The peptide-arrays revealed two
      distinct high binding areas as well as some regions of lower affinity in PrPC
      resulting in total in 7 distinct amino acid sequences (AAs). The first high
      binding area comprises sheep-PrP peptides 43-102 (AA 43-116), including the N
      terminal octarepeats. The second high binding area of sheep-PrP peptides 134-177
      (AA 134-191), encompasses most of the scrapie susceptibility-associated
      polymorphisms in sheep. This concurs with previous studies showing that scrapie
      associated-polymorphisms do not modulate the initial binding of PrPC to PrPSc.
      Comparison of ovine - and bovine peptide-array binding patterns revealed that
      amino acid specific differences can influence the MBP-PrP binding pattern. PrP
      specific antibodies were capable to completely block interaction between the
      peptide-array and MBP-PrP. MBP-PrP was also capable to specifically bind to PrP
      in a Western blot approach. The octarepeat region of PrP seems primarily
      important for this interaction because proteinase K pre-treatment of PrPSc
      completely abolished binding. CONCLUSION: Binding of MBP-PrP to PrP-specific
      sequences indicate that several specific self-interactions between individual PrP
      molecules can occur and suggest that an array of interactions between PrPC-PrPC
      as well as PrPC-PrPSc may be possible, which ultimately lead to variations in
      species barrier and strain differences.

PMID- 17430580
TI  - Early sexual maturation, central adiposity and subsequent overweight in late
      adolescence. a four-year follow-up of 1605 adolescent Norwegian boys and girls:
      the Young HUNT study.
AB  - BACKGROUND: Early sexual maturation has been associated with overweight that may
      persist after the completion of biological growth and development. We have
      prospectively examined the influence of early sexual maturation on subsequent
      overweight in late adolescence and assessed if this association was modified by
      central adiposity in early adolescence. METHODS: 1605 Norwegian adolescents were
      followed from early (baseline, mean age 14.2 years) to late adolescence (follow
      up, mean age 18.2 years). Maturational timing was assessed by self-reports of
      pubertal status (PDS) in boys and age at menarche (AAM) in girls. Central
      adiposity was classified according to waist circumference (waist) measured at
      baseline, using age and gender specific medians as cut off. Overweight was
      classified according to International Obesity Task Force (IOTF) standards.
      RESULTS: At follow-up, early sexual maturation in girls, but not in boys, was
      associated with overweight. This association, however, was restricted to girls
      with high waist circumference (> median) at baseline (OR, 2.7, 95% CI 1.5-4.9).
      Thus, age at menarche was not associated with overweight in girls with low waist
      (< or = median) at baseline. Central adiposity was, independent of maturational
      timing, associated with higher BMI at follow-up in both genders, but differences
      were more pronounced among early matured girls (3.5 kg/m2), than among
      intermediate (2.7 kg/m2) and late matured girls (1.2 kg/m2). CONCLUSION: In
      girls, the combination of central adiposity and early age at menarche appears to
      increase the risk of being overweight in late adolescence.

PMID- 17430581
TI  - Self-reported drinking and driving amongst educated adults in Spain: The
      "Seguimiento Universidad de Navarra" (SUN) cohort findings.
AB  - BACKGROUND: The role of alcohol as a risk factor for motor vehicle crashes is
      long known. Yet, reports on the prevalence of drinking and driving suggest values
      between 20%-30% when the adult driving population is interviewed. We wondered
      whether these values hold true among European educated citizens and whether there
      are any significant differences in prevalence by age, gender, type of profession
      and other lifestyle indicators. METHODS: Cross-sectional analyses of baseline
      data from a cohort of university graduates in Spain (SUN study). Answered
      questionnaires contained items on current drinking and driving practices,
      together with data on socio-demographic characteristics and lifestyle habits. Chi
      square, Fisher test, and multivariate logistic regression were used to
      investigate the impact of several variables on drinking and driving practices.
      Analyses were stratified by gender. RESULTS: Almost 30% of the participants
      reported "sometimes" drinking and driving. This percent increased to 47% when
      "almost never" was also included as a positive answer to the drinking and driving
      practice question. These percentages varied significantly by gender, with up to
      64% of men reporting "sometimes" or "almost never" vs. 36% of women doing so.
      Drinking and driving practices also differed by overall alcohol consumption
      habits, smoking, use of safety belts, and notably, type of profession.
      CONCLUSION: Our findings are amongst the first on the high prevalence of drinking
      and driving among Spanish. Particularly worrisome is the fact that health
      professionals reported this habit even at higher rates. Multidisciplinary
      interventions (e.g., legal, educational, economic) are needed to reduce this
      serious health risk.

PMID- 17430582
TI  - Prognostic significance of bcl-2 expression in stage III breast cancer patients
      who had received doxorubicin and cyclophosphamide followed by paclitaxel as
      adjuvant chemotherapy.
AB  - BACKGROUND: Bcl-2 is positively regulated by hormonal receptor pathways in breast
      cancer. A study was conducted to assess the prognostic significances of clinico
      pathologic variables and of ER, PR, p53, c-erbB2, bcl-2, or Ki-67 as markers of
      relapse in breast cancer patients who had received the identical adjuvant therapy
      at a single institution. METHODS: A cohort of 151 curatively resected stage III
      breast cancer patients (M:F = 3:148, median age 46 years) who had 4 or more
      positive lymph nodes and received doxorubicin and cyclophosphamide followed by
      paclitaxel (AC/T) as adjuvant chemotherapy was analyzed for clinico-pathologic
      characteristics including disease-free survival (DFS) and overall survival (OS).
      Patients with positive ER and/or PR expression received 5 years of tamoxifen
      following AC/T. The protein expressions of biomarkers were assessed
      immunohistochemically. RESULTS: The median follow-up duration was 36 months, and
      37 patients (24.5%) experienced a recurrence. Univariate analyses indicated that
      the tumor size (P = 0.038) and the number of involved lymph nodes (P < 0.001)
      significantly affected the recurrences. However, the type of surgery, the
      histology, histologic grade, the presence of endolymphatic emboli, and a close
      resection margin did not. Moreover, ER positivity (P = 0.013), bcl-2 positivity
      (P = 0.002) and low p53 expression (P = 0.032) were found to be significantly
      associated with a prolonged DFS. Furthermore, multivariate analysis identified 10
      or more involved lymph nodes (HR 7.366; P < 0.001), negative bcl-2 expression (HR
      2.895; P = 0.030), and c-erbB2 over-expression (HR 3.535; P = 0.001) as
      independent indicators of poorer DFS. In addition, bcl-2 expression was found to
      be significantly correlated with the expressions of ER and PR, and inversely
      correlated with the expressions of p53, c-erbB2 and Ki-67. Patients with bcl-2
      expression had a significantly longer DFS than those without, even in the ER (+)
      subgroup. Moreover, OS was significantly affected by ER, bcl-2 and c-erbB2.
      CONCLUSION: Bcl-2 is an independent prognostic factor of DFS in curatively
      resected stage III breast cancer patients and appears to be a useful prognostic
      factor in combination with c-erbB2 and the number of involved lymph nodes.

PMID- 17430583
TI  - Burnout and psychiatric morbidity among medical students entering clinical
      training: a three year prospective questionnaire and interview-based study.
AB  - BACKGROUND: Mental distress among medical students is often reported. Burnout has
      not been studied frequently and studies using interviewer-rated diagnoses as
      outcomes are rarely employed. The objective of this prospective study of medical
      students was to examine clinically significant psychiatric morbidity and burnout
      at 3rd year of medical school, considering personality and study conditions
      measured at 1st year. METHODS: Questionnaires were sent to 127 first year medical
      students who were then followed-up at 3rd year of medical school. Eighty-one of
      3rd year respondents participated in a diagnostic interview. Personality (HP5-i)
      and Performance-based self-esteem (PBSE-scale) were assessed at first year, Study
      conditions (HESI), Burnout (OLBI), Depression (MDI) at 1st and 3rd years.
      Diagnostic interviews (MINI) were used at 3rd year to assess psychiatric
      morbidity. High and low burnout at 3rd year was defined by cluster analysis.
      Logistic regressions were used to identify predictors of high burnout and
      psychiatric morbidity, controlling for gender. RESULTS: 98 (77%) responded on
      both occasions, 80 (63%) of these were interviewed. High burnout was predicted by
      Impulsivity trait, Depressive symptoms at 1st year and Financial concerns at 1st
      year. When controlling for 3rd year study conditions, Impulsivity and concurrent
      Workload remained. Of the interviewed sample 21 (27%) had a psychiatric
      diagnosis, 6 of whom had sought help. Unadjusted analyses showed that psychiatric
      morbidity was predicted by high Performance-based self-esteem, Disengagement and
      Depression at 1st year, only the later remained significant in the adjusted
      analysis. CONCLUSION: Psychiatric morbidity is common in medical students but few
      seek help. Burnout has individual as well as environmental explanations and to
      avoid it, organisational as well as individual interventions may be needed. Early
      signs of depressive symptoms in medical students may be important to address.
      Students should be encouraged to seek help and adequate facilities should be
      available.

PMID- 17430584
TI  - Ethical analysis of the new proposed mental health legislation in England and
      Wales.
AB  - This paper ethically analyses arising out the proposed changes to the Mental
      Health Act for England and Wales. It looks in particular at thea shift in
      philosophy that the author claims has occurred with the proposals away from
      rights-focused principles to more utilitarian or outcome-focused principles. It
      gives examples of these changes and explores its their consequences.

PMID- 17430585
TI  - Generation of clinical grade dendritic cells with capacity to produce
      biologically active IL-12p70.
AB  - BACKGROUND: For optimal T cell activation it is desirable that dendritic cells
      (DCs) display peptides within MHC molecules as signal 1, costimulatory molecules
      as signal 2 and, in addition, produce IL-12p70 as signal 3. IL-12p70 polarizes T
      cell responses towards CD4+ T helper 1 cells, which then support the development
      of CD8+ cytotoxic T lymphocytes. We therefore developed new maturation cocktails
      allowing DCs to produce biologically active IL-12p70 for large-scale cancer
      vaccine development. METHODS: After elutriation of leukapheresis products in a
      closed bag system, enriched monocytes were cultured with GM-CSF and IL-4 for six
      days to generate immature DCs that were then matured with cocktails, containing
      cytokines, interferon-gamma, prostaglandin E2, and a ligand for Toll-like
      receptor 8, with or without poly (I:C). RESULTS: Mature DCs expressed appropriate
      maturation markers and the lymph node homing chemokine receptor, CCR7. They
      retained full maturity after culture for two days without maturation cocktails
      and following cryopreservation. TLR ligand stimulation induced DCs capable of
      secreting IL-12p70 in primary cultures and after one day of coculture with CD40L
      expressing fibroblasts, mimicking an encounter with T cells. DCs matured with our
      new cocktails containing TLR8 ligand, with or without poly (I:C), induced
      alloresponses and stimulated virus-specific T cells after peptide-pulsing. DCs
      matured in cocktails containing TLR8 ligand without poly (I:C) could also be
      loaded with RNA as a source of antigen, whereas DCs matured in cocktails
      containing poly (I:C) were unable to express proteins following RNA transfer by
      electroporation. CONCLUSION: Our new maturation cocktails allowed easy DC
      harvesting, stable maturation and substantial recoveries of mature DCs after
      cryopreservation. Our procedure for generating DCs is easily adaptable for GMP
      compliance and yields IL-12p70-secreting DCs suitable for development of cancer
      vaccines using peptides or RNA as sources of immunizing antigens.

PMID- 17430586
TI  - Mechanism of chimera formation during the Multiple Displacement Amplification
      reaction.
AB  - BACKGROUND: Multiple Displacement Amplification (MDA) is a method used for
      amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal
      for DNA library construction. While this has enabled genomic sequencing from one
      or a few cells of unculturable microorganisms, the process is complicated by the
      tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA.
      Determining the source of the DNA rearrangements would be an important step
      towards reducing or eliminating them. RESULTS: Here, we characterize the major
      types of chimeras formed by carrying out an MDA whole genome amplification from a
      single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of
      475 chimeras revealed the predominant reaction mechanisms that create the DNA
      rearrangements. The highly branched DNA synthesized in MDA can assume many
      alternative secondary structures. DNA strands extended on an initial template can
      be displaced becoming available to prime on a second template creating the
      chimeras. Evidence supports a model in which branch migration can displace 3'
      ends freeing them to prime on the new templates. More than 85% of the resulting
      DNA rearrangements were inverted sequences with intervening deletions that the
      model predicts. Intramolecular rearrangements were favored, with displaced 3'
      ends reannealing to single stranded 5'-strands contained within the same branched
      DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated
      priming at complimentary sequences of 2-21 nucleotides (nts) in the new
      templates. CONCLUSION: Formation of chimeras is an important limitation to the
      MDA method, particularly for whole genome sequencing. Identification of the
      mechanism for chimera formation provides new insight into the MDA reaction and
      suggests methods to reduce chimeras. The 454 sequencing approach used here will
      provide a rapid method to assess the utility of reaction modifications.

PMID- 17430587
TI  - Assessing the reliability of eBURST using simulated populations with known
      ancestry.
AB  - BACKGROUND: The program eBURST uses multilocus sequence typing data to divide
      bacterial populations into groups of closely related strains (clonal complexes),
      predicts the founding genotype of each group, and displays the patterns of recent
      evolutionary descent of all other strains in the group from the founder. The
      reliability of eBURST was evaluated using populations simulated with different
      levels of recombination in which the ancestry of all strains was known. RESULTS:
      For strictly clonal simulations, where all allelic change is due to point
      mutation, the groups of related strains identified by eBURST were very similar to
      those expected from the true ancestry and most of the true ancestor-descendant
      relationships (90-98%) were identified by eBURST. Populations simulated with low
      or moderate levels of recombination showed similarly high performance but the
      reliability of eBURST declined with increasing recombination to mutation ratio.
      Populations simulated under a high recombination to mutation ratio were dominated
      by a single large straggly eBURST group, which resulted from the incorrect
      linking of unrelated groups of strains into the same eBURST group. The
      reliability of the ancestor-descendant links in eBURST diagrams was related to
      the proportion of strains in the largest eBURST group, which provides a useful
      guide to when eBURST is likely to be unreliable. CONCLUSION: Examination of
      eBURST groups within populations of a range of bacterial species showed that most
      were within the range in which eBURST is reliable, and only a small number (e.g.
      Burkholderia pseudomallei and Enterococcus faecium) appeared to have such high
      rates of recombination that eBURST is likely to be unreliable. The study also
      demonstrates how three simple tests in eBURST v3 can be used to detect unreliable
      eBURST performance and recognise populations in which there appears to be a high
      rate of recombination relative to mutation.

PMID- 17430588
TI  - Can visco-elastic phase separation, macromolecular crowding and colloidal physics
      explain nuclear organisation?
AB  - BACKGROUND: The cell nucleus is highly compartmentalized with well-defined
      domains, it is not well understood how this nuclear order is maintained. Many
      scientists are fascinated by the different set of structures observed in the
      nucleus to attribute functions to them. In order to distinguish functional
      compartments from non-functional aggregates, I believe is important to
      investigate the biophysical nature of nuclear organisation. RESULTS: The various
      nuclear compartments can be divided broadly as chromatin or protein and/or RNA
      based, and they have very different dynamic properties. The chromatin compartment
      displays a slow, constrained diffusional motion. On the other hand, the
      protein/RNA compartment is very dynamic. Physical systems with dynamical
      asymmetry go to viscoelastic phase separation. This phase separation phenomenon
      leads to the formation of a long-lived interaction network of slow components
      (chromatin) scattered within domains rich in fast components (protein/RNA).
      Moreover, the nucleus is packed with macromolecules in the order of 300 mg/ml.
      This high concentration of macromolecules produces volume exclusion effects that
      enhance attractive interactions between macromolecules, known as macromolecular
      crowding, which favours the formation of compartments. In this paper I
      hypothesise that nuclear compartmentalization can be explained by viscoelastic
      phase separation of the dynamically different nuclear components, in combination
      with macromolecular crowding and the properties of colloidal particles.
      CONCLUSION: I demonstrate that nuclear structure can satisfy the predictions of
      this hypothesis. I discuss the functional implications of this phenomenon.

PMID- 17430590
TI  - The silent defense: micro-RNA directed defense against HIV-1 replication.
AB  - MicroRNAs play critical role in regulating gene expression. MicroRNA profile of
      particular cell type bears the signature of cell type specific gene expression.
      Given that viral pathogens replicate by evading host defenses, research is now
      focused on the miRNA-regulated genes that critically regulate HIV-1 propagation
      in human host cells.

PMID- 17430589
TI  - Intracerebroventricular antisense knockdown of G alpha i2 results in ciliary
      stasis and ventricular dilatation in the rat.
AB  - BACKGROUND: In the CNS, the heterotrimeric G protein Galphai2 is a minor Galpha
      subunit with restricted localization in the ventricular regions including the
      ependymal cilia. The localization of Galphai2 is conserved in cilia of different
      tissues, suggesting a particular role in ciliary function. Although studies with
      Galphai2-knockout mice have provided information on the role of this Galpha
      subunit in peripheral tissues, its role in the CNS is largely unknown. We used
      intracerebroventricular (icv) antisense administration to clarify the
      physiological role of Galphai2 in the ventricular system. RESULTS: High
      resolution MRI studies revealed that continuous icv-infusion of Galphai2-specific
      antisense oligonucleotide caused unilateral ventricular dilatation that was
      restricted to the antisense-receiving ventricle. Microscopic analysis
      demonstrated ependymal cell damage and loss of ependymal cilia. Attenuation of
      Galphai2 in ependymal cells was confirmed by immunohistochemistry. Ciliary beat
      frequency measurements on cultured ependymal cells indicated that antisense
      administration resulted in ciliary stasis. CONCLUSION: Our results establish that
      Galphai2 has an essential regulatory role in ciliary function and CSF
      homeostasis.

PMID- 17430591
TI  - Influence of soil minerals on chromium(VI) reduction by sulfide under anoxic
      conditions.
AB  - The effects of soil minerals on chromate (CrVIO42-, noted as Cr(VI)) reduction by
      sulfide were investigated in the pH range of 7.67 to 9.07 under the anoxic
      condition. The examined minerals included montmorillonite (Swy-2), illite (IMt
      2), kaolinite (KGa-2), aluminum oxide (gamma-Al2O3), titanium oxide (TiO2, P-25,
      primarily anatase), and silica (SiO2). Based on their effects on Cr(VI)
      reduction, these minerals were categorized into three groups: (i) minerals
      catalyzing Cr(VI) reduction - illite; (ii) minerals with no effect - Al2O3; and
      (iii) minerals inhibiting Cr(VI) reduction- kaolinite, montmorillonite, SiO2 and
      TiO2 . The catalysis of illite was attributed primarily to the low concentration
      of iron solubilized from the mineral, which could accelerate Cr(VI) reduction by
      shuttling electrons from sulfide to Cr(VI). Additionally, elemental sulfur
      produced as the primary product of sulfide oxidation could further catalyze
      Cr(VI) reduction in the heterogeneous system. Previous studies have shown that
      adsorption of sulfide onto elemental sulfur nanoparticles could greatly increase
      sulfide reactivity towards Cr(VI) reduction. Consequently, the observed rate
      constant, kobs, increased with increasing amounts of both iron solubilized from
      illite and elemental sulfur produced during the reaction. The catalysis of iron,
      however, was found to be blocked by phenanthroline, a strong complexing agent for
      ferrous iron. In this case, the overall reaction rate at the initial stage of
      reaction was pseudo first order with respect to Cr(VI), i.e., the reaction
      kinetics was similar to that in the homogeneous system, because elemental sulfur
      exerted no effect at the initial stage prior to accumulation of elemental sulfur
      nanoparticles. In the suspension of kaolinite, which belonged to group (iii), an
      inhibitive effect to Cr(VI) reduction was observed and subsequently examined in
      more details. The inhibition was due to the sorption of elemental sulfur onto
      kaolinite, which reduced or completely eliminated the catalytic effect of
      elemental sulfur, depending on kaolinite concentration. This was consistent with
      the observation that the catalysis of externally added elemental sulfur (50 muM)
      on Cr(VI) reduction would disappear with a kaolinite concentration of more than
      5.0 g/L. In kaolinite suspension, the overall reaction rate law was:-d[Cr(VI)]/dt
      = kobs[H+]2[Cr(VI)][HS-]0.70.

PMID- 17430592
TI  - Tumoral and non-tumoral trachea stenoses: evaluation with three-dimensional CT
      and virtual bronchoscopy.
AB  - BACKGROUND: We evaluated the ability of 3D-CT and virtual bronchoscopy to
      estimate trachea stenosis in comparison to conventional axial CT and fiberoptic
      bronchoscopy, with a view to assist thoracic surgeons in depicting the anatomical
      characteristics of tracheal strictures. METHODS: Spiral CT was performed in 16
      patients with suspected tracheal stenoses and in 5 normal subjects. Tracheal
      stenoses due to an endoluminal neoplasm were detected in 13 patients, whilst post
      intubation tracheal stricture was observed in the other 3 patients. Multiplanar
      reformatting (MPR), volume rendering techniques (VRT) and virtual endoscopy (VE)
      for trachea evaluation were applied and findings were compared to axial CT and
      fiberoptic bronchoscopy. The accuracy of the procedure in describing the
      localization and degree of stenosis was tested by two radiologists in a blinded
      controlled trial. RESULTS: The imaging modalities tested showed the same stenoses
      as the ones detected by flexible bronchoscopy and achieved accurate and non
      invasive morphological characterization of the strictures, as well as additional
      information about the extraluminal extent of the disease. No statistically
      significant difference was observed between the bronchoscopic findings and the
      results of axial CT estimations (P = 1.0). No statistically significant
      differences were observed between bronchoscopic findings and the MPR, VRT and VE
      image evaluations (P = 0.705, 0.414 and 0.414 respectively). CONCLUSION: CT and
      computed generated images may provide a high fidelity, noninvasive and
      reproducible evaluation of the trachea compared to bronchoscopy. They may play a
      role in assessment of airway patency distal to high-grade stenoses, and represent
      a reliable alternative method for patients not amenable to conventional
      bronchoscopy.

PMID- 17430593
TI  - Genetic fixity in the human major histocompatibility complex and block size
      diversity in the class I region including HLA-E.
AB  - BACKGROUND: The definition of human MHC class I haplotypes through association of
      HLA-A, HLA-Cw and HLA-B has been used to analyze ethnicity, population migrations
      and disease association. RESULTS: Here, we present HLA-E allele haplotype
      association and population linkage disequilibrium (LD) analysis within the ~1.3
      Mb bounded by HLA-B/Cw and HLA-A to increase the resolution of identified class I
      haplotypes. Through local breakdown of LD, we inferred ancestral recombination
      points both upstream and downstream of HLA-E contributing to alternative block
      structures within previously identified haplotypes. Through single nucleotide
      polymorphism (SNP) analysis of the MHC region, we also confirmed the essential
      genetic fixity, previously inferred by MHC allele analysis, of three conserved
      extended haplotypes (CEHs), and we demonstrated that commercially-available SNP
      analysis can be used in the MHC to help define CEHs and CEH fragments.
      CONCLUSION: We conclude that to generate high-resolution maps for relating MHC
      haplotypes to disease susceptibility, both SNP and MHC allele analysis must be
      conducted as complementary techniques.

PMID- 17430594
TI  - Gene expression profiles of prostate cancer reveal involvement of multiple
      molecular pathways in the metastatic process.
AB  - BACKGROUND: Prostate cancer is characterized by heterogeneity in the clinical
      course that often does not correlate with morphologic features of the tumor.
      Metastasis reflects the most adverse outcome of prostate cancer, and to date
      there are no reliable morphologic features or serum biomarkers that can reliably
      predict which patients are at higher risk of developing metastatic disease.
      Understanding the differences in the biology of metastatic and organ confined
      primary tumors is essential for developing new prognostic markers and therapeutic
      targets. METHODS: Using Affymetrix oligonucleotide arrays, we analyzed gene
      expression profiles of 24 androgen-ablation resistant metastatic samples obtained
      from 4 patients and a previously published dataset of 64 primary prostate tumor
      samples. Differential gene expression was analyzed after removing potentially
      uninformative stromal genes, addressing the differences in cellular content
      between primary and metastatic tumors. RESULTS: The metastatic samples are highly
      heterogenous in expression; however, differential expression analysis shows that
      415 genes are upregulated and 364 genes are downregulated at least 2 fold in
      every patient with metastasis. The expression profile of metastatic samples
      reveals changes in expression of a unique set of genes representing both the
      androgen ablation related pathways and other metastasis related gene networks
      such as cell adhesion, bone remodelling and cell cycle. The differentially
      expressed genes include metabolic enzymes, transcription factors such as Forkhead
      Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1).
      CONCLUSION: We hypothesize that these genes have a role in the biology of
      metastatic disease and that they represent potential therapeutic targets for
      prostate cancer.

PMID- 17430595
TI  - Virus-induced gene silencing as a tool for functional analyses in the emerging
      model plant Aquilegia (columbine, Ranunculaceae).
AB  - BACKGROUND: The lower eudicot genus Aquilegia, commonly known as columbine, is
      currently the subject of extensive genetic and genomic research aimed at
      developing this taxon as a new model for the study of ecology and evolution. The
      ability to perform functional genetic analyses is a critical component of this
      development process and ultimately has the potential to provide insight into the
      genetic basis for the evolution of a wide array of traits that differentiate
      flowering plants. Aquilegia is of particular interest due to both its recent
      evolutionary history, which involves a rapid adaptive radiation, and its
      intermediate phylogenetic position between core eudicot (e.g., Arabidopsis) and
      grass (e.g., Oryza) model species. RESULTS: Here we demonstrate the effective use
      of a reverse genetic technique, virus-induced gene silencing (VIGS), to study
      gene function in this emerging model plant. Using Agrobacterium mediated transfer
      of tobacco rattle virus (TRV) based vectors, we induce silencing of PHYTOENE
      DESATURASE (AqPDS) in Aquilegia vulgaris seedlings, and ANTHOCYANIDIN SYNTHASE
      (AqANS) and the B-class floral organ identity gene PISTILLATA in A. vulgaris
      flowers. For all of these genes, silencing phenotypes are associated with
      consistent reduction in endogenous transcript levels. In addition, we show that
      silencing of AqANS has no effect on overall floral morphology and is therefore a
      suitable marker for the identification of silenced flowers in dual-locus
      silencing experiments. CONCLUSION: Our results show that TRV-VIGS in Aquilegia
      vulgaris allows data to be rapidly obtained and can be reproduced with effective
      survival and silencing rates. Furthermore, this method can successfully be used
      to evaluate the function of early-acting developmental genes. In the future, data
      derived from VIGS analyses will be combined with large-scale sequencing and
      microarray experiments already underway in order to address both recent and
      ancient evolutionary questions.

PMID- 17430597
TI  - Apolipoprotein E levels in cerebrospinal fluid and the effects of ABCA1
      polymorphisms.
AB  - BACKGROUND: Animal studies suggest that brain apolipoprotein E (apoE) levels
      influence amyloid-beta (Abeta) deposition and thus risk for Alzheimer's disease
      (AD). We have previously demonstrated that deletion of the ATP-binding cassette
      A1 transporter (ABCA1) in mice causes dramatic reductions in brain and
      cerebrospinal fluid (CSF) apoE levels and lipidation. To examine whether
      polymorphisms in ABCA1 affect CSF apoE levels in humans, we measured apoE in CSF
      taken from 168 subjects who were 43 to 91 years old and were either cognitively
      normal or who had mild AD. We then genotyped the subjects for ten previously
      identified ABCA1 single nucleotide polymorphisms (SNPs). RESULTS: In all
      subjects, the mean CSF apoE level was 9.09 microg/ml with a standard deviation of
      2.70 microg/ml. Levels of apoE in CSF samples taken from the same individual two
      weeks apart were strongly correlated (r2 = 0.93, p < 0.01). In contrast, CSF apoE
      levels in different individuals varied widely (coefficient of variation = 46%).
      CSF apoE levels did not vary according to AD status, APOE genotype, gender or
      race. Average apoE levels increased with age by approximately 0.5 microg/ml per
      10 years (r2 = 0.05, p = 0.003). We found no significant associations between CSF
      apoE levels and the ten ABCA1 SNPs we genotyped. Moreover, in a separate sample
      of 1225 AD cases and 1431 controls, we found no association between the ABCA1 SNP
      rs2230806 and AD as has been previously reported. CONCLUSION: We found that CSF
      apoE levels vary widely between individuals, but are stable within individuals
      over a two-week interval. AD status, APOE genotype, gender and race do not affect
      CSF apoE levels, but average CSF apoE levels increase with age. Given the lack of
      association between CSF apoE levels and genotypes for the ABCA1 SNPs we examined,
      either these SNPs do not affect ABCA1 function or if they do, they do not have
      strong effects in the CNS. Finally, we find no evidence for an association
      between the ABCA1 SNP rs2230806 and AD in a large sample set.

PMID- 17430598
TI  - Vacuum-assisted closure therapy in ureteroileal anastomotic leakage after
      surgical therapy of bladder cancer.
AB  - BACKGROUND: Vacuum-assisted closure (VAC) is an acknowledged method of treating
      wound healing disorders, but has been viewed as a contraindication in therapy of
      intraabdominal fistulas. CASE PRESENTATION: We present the case of an 83-year old
      patient with ureteroileal anastomotic insufficiency following cystectomy and
      urinary diversion by Bricker ileal conduit due to urothelial bladder cancer.
      After developing an open abdomen on the 16th postoperative day a leakage of the
      ureteroileal anastomosis appeared that cannot be managed by surgical means. To
      stop the continued leakage we tried a modified VAC therapy with a silicon covered
      polyurethane foam under a suction of 125 mmHg. After 32 days with regularly
      changes of the VAC foam under general anesthesia the fistula resolved without
      further problems of ureteroileal leakage. CONCLUSION: We present the first report
      of VAC therapy successfully performed in urinary tract leakage after surgical
      treatment of bladder cancer. VAC therapy of such disorders requires greater care
      than of superficial application to avoid mechanical alterations of internal
      organs but opens new opportunities in cases without surgical alternatives.

PMID- 17430596
TI  - Adenovirus type 5 exerts genome-wide control over cellular programs governing
      proliferation, quiescence, and survival.
AB  - BACKGROUND: Human adenoviruses, such as serotype 5 (Ad5), encode several proteins
      that can perturb cellular mechanisms that regulate cell cycle progression and
      apoptosis, as well as those that mediate mRNA production and translation.
      However, a global view of the effects of Ad5 infection on such programs in normal
      human cells is not available, despite widespread efforts to develop adenoviruses
      for therapeutic applications. RESULTS: We used two-color hybridization and
      oligonucleotide microarrays to monitor changes in cellular RNA concentrations as
      a function of time after Ad5 infection of quiescent, normal human fibroblasts. We
      observed that the expression of some 2,000 genes, about 10% of those examined,
      increased or decreased by a factor of two or greater following Ad5 infection, but
      were not altered in mock-infected cells. Consensus k-means clustering established
      that the temporal patterns of these changes were unexpectedly complex. Gene
      Ontology terms associated with cell proliferation were significantly over
      represented in several clusters. The results of comparative analyses demonstrate
      that Ad5 infection induces reversal of the quiescence program and recapitulation
      of the core serum response, and that only a small subset of the observed changes
      in cellular gene expression can be ascribed to well characterized functions of
      the viral E1A and E1B proteins. CONCLUSION: These findings establish that the
      impact of adenovirus infection on host cell programs is far greater than
      appreciated hitherto. Furthermore, they provide a new framework for investigating
      the molecular functions of viral early proteins and information relevant to the
      design of conditionally replicating adenoviral vectors.

PMID- 17430599
TI  - IMRT in oral cavity cancer.
AB  - BACKGROUND: Except for early T1,2 N0 stages, the prognosis for patients with oral
      cavity cancer (OCC) is reported to be worse than for carcinoma in other sites of
      the head and neck (HNC). The aim of this work was to assess disease outcome in
      OCC following IMRT.Between January 2002 and January 2007, 346 HNC patients have
      been treated with curative intensity modulated radiation therapy (IMRT) at the
      Department of Radiation Oncology, University Hospital Zurich. Fifty eight of
      these (16%) were referred for postoperative (28) or definitive (30) radiation
      therapy of OCC.40 of the 58 OCC patients (69%) presented with locally advanced
      T3/4 or recurred lesions. Doses between 60 and 70 Gy were applied, combined with
      simultaneous cisplatin based chemotherapy in 78%. Outcome analyses were performed
      using Kaplan Meier curves.In addition, comparisons were performed between this
      IMRT OCC cohort and historic in-house cohorts of 33 conventionally irradiated
      (3DCRT) and 30 surgery only patients treated over the last 10 years. RESULTS: OCC
      patients treated with postoperative IMRT showed the highest local control (LC)
      rate of all assessed treatment sequence subgroups (92% LC at 2 years). Historic
      postoperative 3DCRT patients and patients treated with surgery alone reached LC
      rates of approximately 70-80%. Definitively irradiated patients revealed poorest
      LC rates with approximately 30 and 40% following 3DCRT and IMRT, respectively.T1
      stage resulted in an expectedly significantly higher LC rate (95%, n = 19, p <
      0.05) than T2-4 and recurred stages (LC approximately 50-60%, n = 102).Analyses
      according to the diagnosis revealed significantly lower LC in OCC following
      definitive IMRT than that in pharyngeal tumors treated with definitive IMRT in
      the same time period (43% vs 82% at 2 years, p < 0.0001), while the LC rate of
      OCC following postoperative IMRT was as high as in pharyngeal tumors treated with
      postoperative IMRT (>90% at 2 years). CONCLUSION: Postoperative IMRT of OCC
      resulted in the highest local control rate of the assessed treatment subgroups.
      In conclusion, generous indication for IMRT following surgical treatment is
      recommended in OCC cases with unfavourable features like tight surgical margin,
      nodal involvement, primary tumor stage >T1N0, or already recurred disease,
      respectively.Loco-regional outcome of OCC following definitive IMRT remained
      unsatisfactory, comparable to that following definitive 3DCRT.

PMID- 17430600
TI  - Deletion of the cruciform binding domain in CBP/14-3-3 displays reduced origin
      binding and initiation of DNA replication in budding yeast.
AB  - BACKGROUND: Initiation of eukaryotic DNA replication involves many protein
      protein and protein-DNA interactions. We have previously shown that 14-3-3
      proteins bind cruciform DNA and associate with mammalian and yeast replication
      origins in a cell cycle dependent manner. RESULTS: By expressing the human 14-3
      3epsilon, as the sole member of 14-3-3 proteins family in Saccharomyces
      cerevisiae, we show that 14-3-3epsilon complements the S. cerevisiae Bmh1/Bmh2
      double knockout, conserves its cruciform binding activity, and associates in vivo
      with the yeast replication origins ARS307. Deletion of the alpha5-helix, the
      potential cruciform binding domain of 14-3-3, decreased the cruciform binding
      activity of the protein as well as its association with the yeast replication
      origins ARS307 and ARS1. Furthermore, the mutant cells had a reduced ability to
      stably maintain plasmids bearing one or multiple origins. CONCLUSION: 14-3-3, a
      cruciform DNA binding protein, associates with yeast origins of replication and
      functions as an initiator of DNA replication, presumably through binding to
      cruciform DNA forming at yeast replicators.

PMID- 17430601
TI  - pax1-1 partially suppresses gain-of-function mutations in Arabidopsis AXR3/IAA17.
AB  - BACKGROUND: The plant hormone auxin exerts many of its effects on growth and
      development by controlling transcription of downstream genes. The Arabidopsis
      gene AXR3/IAA17 encodes a member of the Aux/IAA family of auxin responsive
      transcriptional repressors. Semi-dominant mutations in AXR3 result in an
      increased amplitude of auxin responses due to hyperstabilisation of the encoded
      protein. The aim of this study was to identify novel genes involved in auxin
      signal transduction by screening for second site mutations that modify the axr3-1
      gain-of-function phenotype. RESULTS: We present the isolation of the partial
      suppressor of axr3-1 (pax1-1) mutant, which partially suppresses almost every
      aspect of the axr3-1 phenotype, and that of the weaker axr3-3 allele. axr3-1
      protein turnover does not appear to be altered by pax1-1. However, expression of
      an AXR3::GUS reporter is reduced in a pax1-1 background, suggesting that PAX1
      positively regulates AXR3 transcription. The pax1-1 mutation also affects the
      phenotypes conferred by stabilising mutations in other Aux/IAA proteins; however,
      the interactions are more complex than with axr3-1. CONCLUSION: We propose that
      PAX1 influences auxin response via its effects on AXR3 expression and that it
      regulates other Aux/IAAs secondarily.

PMID- 17430603
TI  - Congenital malaria with atypical presentation: a case report from low
      transmission area in India.
AB  - BACKGROUND: Malaria during first few months of life may be due to transplacental
      transfer of parasitized maternal erythrocytes. Although IgG and IgM antimalarial
      antibodies can be detected in maternal blood, only IgG antibodies are present in
      the infant's blood. These antibodies can delay and modify the onset of clinical
      manifestations. CASE PRESENTATION: An infant is described who presented with
      irritability and feeding problems. Clinical examination and investigations
      revealed that the infant was afebrile, had jaundice, hepatosplenomegaly and
      haemolytic anaemia. Peripheral smear demonstrated Plasmodium vivax. While the
      mother had significant levels of immunoglobulin G (IgG), the infant was found
      negative for IgG and had low immunoglobulin M (IgM) levels. The mother had a
      history of febrile illness during pregnancy and her peripheral smear was also
      positive for P. vivax. Both were successfully treated with chloroquine in the
      dose of 25 mg/kg/day over three days. CONCLUSION: The case emphasizes the
      importance of considering the diagnosis of malaria even in infants in low
      transmission area, who may not present with typical symptoms of malaria, such as
      fever, but have other clinical manifestations like jaundice and haemolytic
      anaemia.

PMID- 17430602
TI  - Mild gestational diabetes in pregnancy and the adipoinsular axis in babies born
      to mothers in the ACHOIS randomised controlled trial.
AB  - BACKGROUND: Mild gestational diabetes is a common complication of pregnancy,
      affecting up to 9% of pregnant women. Treatment of mild GDM is known to reduce
      adverse perinatal outcomes such as macrosomia and associated birth injuries, such
      as shoulder dystocia, bone fractures and nerve palsies. This study aimed to
      compare the plasma glucose concentrations and serum insulin, leptin and
      adiponectin in cord blood of babies of women (a) without gestational diabetes
      mellitus (GDM), (b) with mild GDM under routine care, or (c) mild GDM with
      treatment. METHODS: 95 women with mild GDM on oral glucose tolerance testing
      (OGTT) at one tertiary level maternity hospital who had been recruited to the
      ACHOIS trial at one of the collaborating hospitals and randomised to either
      Treatment (n = 46) or Routine Care (n = 49) and Control women with a normal OGTT
      (n = 133) were included in the study. Women with mild GDM (treatment or routine
      care group) and OGTT normal women received routine pregnancy care. In addition,
      women with treated mild GDM received dietary advice, blood glucose monitoring and
      insulin if necessary. The primary outcome measures were cord blood concentrations
      of glucose, insulin, adiponectin and leptin. RESULTS: Cord plasma glucose was
      higher in women receiving routine care compared with control, but was normalized
      by treatment for mild GDM (p = 0.01). Cord serum insulin and insulin to glucose
      ratio were similar between the three groups. Leptin concentration in cord serum
      was lower in GDM treated women compared with routine care (p = 0.02) and not
      different to control (p = 0.11). Adiponectin was lower in both mild GDM groups
      compared with control (Treatment p = 0.02 and Routine Care p = 0.07), while the
      adiponectin to leptin ratio was lower for women receiving routine care compared
      with treatment (p = 0.08) and control (p = 0.05). CONCLUSION: Treatment of women
      with mild GDM using diet, blood glucose monitoring and insulin if necessary,
      influences the altered fetal adipoinsular axis characteristic of mild GDM in
      pregnancy.

PMID- 17430604
TI  - When S-cones contribute to chromatic global motion processing.
AB  - There is common consensus now that color-defined motion can be perceived by the
      human visual system. For global motion integration tasks based on isoluminant
      random dot kinematograms conflicting evidence exists, whether observers can
      (Ruppertsberg et al., 2003) or cannot (Bilodeau & Faubert, 1999) extract a common
      motion direction for stimuli modulated along the isoluminant red-green axis. Here
      we report conditions, in which S-cones contribute to chromatic global motion
      processing. When the display included extra-foveal regions, the individual
      elements were large ( approximately 0.3 degrees ) and the displacement was large
      ( approximately 1 degrees ), stimuli modulated along the yellowish-violet axis
      proved to be effective in a global motion task. The color contrast thresholds for
      detection for both color axes were well below the contrasts required for global
      motion integration, and therefore the discrimination-to-detection ratio was >1.
      We conclude that there is significant S-cone input to chromatic global motion
      processing and the extraction of global motion is not mediated by the same
      mechanism as simple detection. Whether the koniocellular or the magnocellular
      pathway is involved in transmitting S-cone signals is a topic of current debate
      (Chatterjee & Callaway, 2002).

PMID- 17430605
TI  - Evidence that L-AP5 and D,L-AP4 can preferentially block cone signals in the rat
      retina.
AB  - Several lines of evidence suggest that, as concentrations of two agonists of
      group III metabotropic glutamate receptors are increased, cone contributions to
      the b-wave are blocked before rod contributions. Application of L-AP5 (L-2-amino
      5-phosphonobutyric acid) at concentrations of 50 microM and D,L-AP4 (D,L-2-amino
      4-phosphonobutyric acid) at concentrations 2 microM had a greater effect in
      reducing the amplitude of the rat ERG b-wave at high light intensities than at
      low light intensities. The amplitude reduction occurs at flash intensities that
      saturate rod photoreceptor responses. When steady backgrounds are used to
      saturate rod photoreceptors, the b-wave responses show increased long-wavelength
      sensitivity. Responses on a rod saturating background are blocked by adding L-AP5
      or AP4 at the above concentrations to the perfusate. Further evidence for
      metabotrophic receptors being involved comes from the observation that even when
      ionotropic glutamate receptors are pharmacologically blocked with MK801 and DNQX,
      AP4 selectively blocks cone contributions to the b-wave. Thus we suggest that the
      type III metabotrophic receptors on depolarizing cone bipolar cells or cone
      synaptic terminals are affected by concentrations of L-AP5 and D,L-AP4 that have
      minimal effects on rod bipolar cells or rod synaptic terminals.

PMID- 17430606
TI  - Naturalistic color discriminations in polymorphic platyrrhine monkeys: effects of
      stimulus luminance and duration examined with functional substitution.
AB  - X-linked photopigment polymorphism produces six different color vision phenotypes
      in most species of New World monkey. In the subfamily Callitrichinae, the three
      M/L alleles underlying these different phenotypes are present at unequal
      frequencies suggesting that selective pressures other than heterozygous-advantage
      operate on these alleles. Earlier we investigated this hypothesis with functional
      substitution, a technique using a computer monitor to simulate colors as they
      would appear to humans with monkey visual pigments (Visual Neuroscience 21:217
      222, 2004). The stimuli were derived from measurements of ecologically relevant
      fruit and foliage. We found that discrimination performance depended on the
      relative spectral positioning of the substituted M and L pigment pair. Here we
      have undertaken a systematic examination of two simulation parameters--test field
      luminance and stimulus duration. Discriminability of the fruit colors depended on
      which phenotype was simulated but only at short stimulus durations and/or low
      luminances. Under such conditions, phenotypes with the larger pigment peak
      separations performed better. At longer durations and higher luminances,
      differences in performance across different substitutions tended to disappear.
      The stimuli used in this experiment were analyzed with several color
      discrimination models. There was limited agreement among the predictions made by
      these models regarding the capabilities of animals with different pigment pairs
      and none predicted the dependence of discrimination on changes in luminance and
      stimulus duration.

PMID- 17430607
TI  - Endocannabinoid signaling regulates spontaneous transmitter release from
      embryonic retinal amacrine cells.
AB  - GABAergic amacrine cells, cultured from embryonic chick retina, display
      spontaneous mini frequencies ranging from 0-4.6 Hz as a result of the release of
      quanta of transmitter from both synapses and autapses. We show here that at least
      part of this variation originates from differences in the degree to which
      endocannabinoids, endogenously generated within the culture, are present at
      terminals presynaptic to individual cells. Though all cells examined scored
      positive for cannabinoid receptor type I (CB1R), only those showing a low initial
      rate of spontaneous minis responded to CB1R agonists with an increase in mini
      frequency, caused by a Gi/o-mediated reduction in [cAMP]. Cells displaying a high
      initial rate of spontaneous minis, on the other hand, were unaffected by CB1R
      agonists, but they did show a rate decrease with CB1R antagonists. Such a
      regulation of spontaneous transmitter release by endocannabinoids might be
      important in network maintenance in amacrine cells and other inhibitory
      interneurons.

PMID- 17430608
TI  - Low-voltage activated calcium currents in ganglion cells of the tiger salamander
      retina: experiment and simulation.
AB  - We examined the functional properties of a low-voltage-activated (LVA) calcium
      current in ganglion cells of the neotenous tiger salamander (Ambystoma tigrinum)
      retina. Our analysis was based on whole-cell recordings from acutely dissociated
      ganglion cell bodies identified by retrograde dye injections. Using a
      continuously perfused cell preparation, the LVA current was isolated with the use
      of potassium channel blocking agents added to the bathing medium and the pipette
      solution, while tetrodotoxin was added to the bathing medium to block Na+
      channels. Approximately 70% of ganglion cells had an easily identified LVA
      current. The LVA current activated at membrane potentials more positive than -90
      mV, and inactivated rapidly. It was relatively insensitive to nickel (IC50 > 500
      microM) and amiloride (IC50 > 750 microM). Voltage- and current-clamp studies
      allowed us to generate a model of this current using the NEURON simulation
      program. Studies were also carried out to measure the LVA Ca2+ current in
      ganglion cells with dendrites to confirm that it had a significant dendritic
      representation. Physiological mechanisms that may depend on LVA Ca2+ currents are
      discussed with an emphasis on the role that dendrites play in ganglion cell
      function.

PMID- 17430610
TI  - Neuronal response to texture- and contrast-defined boundaries in early visual
      cortex.
AB  - Natural scenes contain a variety of visual cues that facilitate boundary
      perception (e.g., luminance, contrast, and texture). Here we explore whether
      single neurons in early visual cortex can process both contrast and texture cues.
      We recorded neural responses in cat A18 to both illusory contours formed by
      abutting gratings (ICs, texture-defined) and contrast-modulated gratings (CMs,
      contrast-defined). We found that if a neuron responded to one of the two stimuli,
      it also responded to the other. These neurons signaled similar contour
      orientation, spatial frequency, and movement direction of the two stimuli. A
      given neuron also exhibited similar selectivity for spatial frequency of the
      fine, stationary grating components (carriers) of the stimuli. These results
      suggest that the cue-invariance of early cortical neurons extends to different
      kinds of texture or contrast cues, and might arise from a common nonlinear
      mechanism.

PMID- 17430609
TI  - Complex motion selectivity in PMLS cortex following early lesions of primary
      visual cortex in the cat.
AB  - In the cat, the analysis of visual motion cues has generally been attributed to
      the posteromedial lateral suprasylvian cortex (PMLS) (Toyama et al., 1985;
      Rauschecker et al., 1987; Rauschecker, 1988; Kim et al., 1997). The responses of
      neurons in this area are not critically dependent on inputs from the primary
      visual cortex (VC), as lesions of VC leave neuronal response properties in PMLS
      relatively unchanged (Spear & Baumann, 1979; Spear, 1988; Guido et al., 1990b).
      However, previous studies have used a limited range of visual stimuli. In this
      study, we assessed whether neurons in PMLS cortex remained direction-selective to
      complex motion stimuli following a lesion of VC, particularly to complex random
      dot kinematograms (RDKs). Unilateral aspiration of VC was performed on post-natal
      days 7-9. Single unit extracellular recordings were performed one year later in
      the ipsilateral PMLS cortex. As in previous studies, a reduction in the
      percentage of direction selective neurons was observed with drifting sinewave
      gratings. We report a previously unobserved phenomenon with sinewave gratings, in
      which there is a greater modulation of firing rate at the temporal frequency of
      the stimulus in animals with a lesion of VC, suggesting an increased segregation
      of ON and OFF sub-regions. A significant portion of neurons in PMLS cortex were
      direction selective to simple (16/18) and complex (11/16) RDKs. However, the
      strength of direction selectivity to both stimuli was reduced as compared to
      normals. The data suggest that complex motion processing is still present, albeit
      reduced, in PMLS cortex despite the removal of VC input. The complex RDK motion
      selectivity is consistent with both geniculo-cortical and extra-geniculate
      thalamo-cortical pathways in residual direction encoding.

PMID- 17430611
TI  - Normal and rebound impulse firing in retinal ganglion cells.
AB  - Given that the action potential output of retinal ganglion cells (RGCs)
      determines the nature of the visual information that is transmitted from the
      retina, an understanding of their intrinsic impulse firing characteristics is
      critical for an appreciation of the overall processing of visual information.
      Recordings from RGCs within an isolated whole-mount retina preparation showed
      that their normal impulse firing from the resting membrane potential (RMP) was
      linearly correlated in its frequency with the stimulus intensity. In addition to
      describing the relationship between the magnitude of the current injection and
      the resulting impulse frequency (F/I relationship), we have characterized the
      properties of individual action potentials when they are elicited from the RMP.
      In contrast, hyperpolarizing below the RMP revealed that RGCs displayed a time
      dependent anomalous rectification, manifested by the appearance of a depolarizing
      sag in their voltage response. When an adequate period of hyperpolarization was
      terminated, a fast phasic period of "rebound excitation" was observed,
      characterized by a brief phasic burst of impulse activity. When compared to
      equivalent action potential firing evoked by depolarizing from the RMP, rebound
      spiking was associated with a lower threshold and shorter latency for impulse
      activation as well as a prominent, phasic, burst-like doublet, or triplet of
      impulses. The rebound action potential had a more positive voltage overshoot and
      displayed a higher peak rate of rise in its upstroke than those correspondingly
      generated by depolarizing current pulses from the RMP. Blocking sodium spikes
      with TTX confirmed that the preceding hyperpolarization led to the recruitment
      and subsequent generation of a transient depolarizing voltage overshoot, which we
      have termed the net depolarizing overshoot (NDO). We propose that the NDO boosts
      the generation of sodium spikes by triggering rebound spikes on its upstroke and
      crest, thus accounting for the observed voltage dependent change in the firing
      pattern of RGCs.

PMID- 17430612
TI  - A three-dimensional analysis of the development of the horizontal cell mosaic in
      the rat retina: implications for the mechanisms controlling pattern formation.
AB  - The horizontal cells are known to form a mono-layered mosaic in the adult retina,
      but are scattered at different retinal depths in early development. To help
      clarifying when and which spatial constraints appear in the relative positioning
      of these cells, we have performed a quantitative analysis of the three
      dimensional (3D) organization of the horizontal cell mosaic at different
      developmental stages in the postnatal rat retina. We first analyzed the two
      dimensional (2D) distribution of the horizontal cell projections onto a plane
      parallel to the upper retinal surface in retinal flat-mounts, and thus to the
      future mature horizontal cell mosaic. We found that this 2D distribution was non
      random since postnatal day 1 (P1), and had a subsequent stepwise improvement in
      regularity. This preceded the alignment of cells in a single monolayer, which was
      observed on P6. We then computed true horizontal cell spacing in 3D, finding non
      random 3D positioning already on P1. Simulation studies showed that this order
      might simply derive from the 2D order observed in the projections of the cells in
      flat-mount, combined with their limited spread in retinal depth. Throughout the
      period analyzed, the relative positions of horizontal cells are in good agreement
      with a minimal spacing rule in which the exclusion zone corresponds to the
      average size of the inner core of the cell dendritic tree estimated from P1
      samples. These data indicate the existence of different phases in the process of
      horizontal cell 3D spatial ordering, supporting the view that multiple mechanisms
      are involved in the development of the horizontal cell mosaic.

PMID- 17430613
TI  - Two expressions of "surround suppression" in V1 that arise independent of
      cortical mechanisms of suppression.
AB  - The preferred stimulus size of a V1 neuron decreases with increases in stimulus
      contrast. It has been supposed that stimulus contrast is the primary determinant
      of such spatial summation in V1 cells, though the extent to which it depends on
      other stimulus attributes such as orientation and spatial frequency remains
      untested. We investigated this by recording from single cells in V1 of
      anaesthetized cats and monkeys, measuring size-tuning curves for high-contrast
      drifting gratings of optimal spatial configuration, and comparing these curves
      with those obtained at lower contrast or at sub-optimal orientations or spatial
      frequencies. For drifting gratings of optimal spatial configuration, lower
      contrasts produced less surround suppression resulting in increases in preferred
      size. High contrast gratings of sub-optimal spatial configuration produced more
      surround suppression than optimal low-contrast gratings, and as much or more
      surround suppression than optimal high-contrast gratings. For sub-optimal spatial
      frequencies, preferred size was similar to that for the optimal high-contrast
      stimulus, whereas for sub-optimal orientations, preferred size was smaller than
      that for the optimal high-contrast stimulus. These results indicate that, while
      contrast is an important determinant of spatial summation in V1, it is not the
      only determinant. Simulation of these experiments on a cortical receptive field
      modeled as a Gabor revealed that the small preferred sizes observed for non
      preferred stimuli could result simply from linear filtering by the classical
      receptive field. Further simulations show that surround suppression in retinal
      ganglion cells and LGN cells can be propagated to neurons in V1, though certain
      properties of the surround seen in cortex indicate that it is not solely
      inherited from earlier stages of processing.

PMID- 17430615
TI  - Principles and practice in ethical review of animal experiments across Europe:
      summary of the report of a FELASA working group on ethical evaluation of animal
      experiments.
AB  - This paper summarizes a more detailed report produced by the Federation of
      European Laboratory Animal Science Associations (FELASA 2005), which describes
      and explores a set of principles for the conduct of ethical review of laboratory
      animal use. It presents a synopsis of results from a questionnaire that elicited
      information on how each of 20 countries represented in FELASA currently
      approaches such ethical review. This information suggests that, although local
      practices differ, there is an emerging consensus on the key elements that any
      ethical review process should involve. Drawing on the questionnaire findings,
      this summary also includes a brief discussion to support and amplify a series of
      recommendations, covering the objectives of ethical review; legal requirements;
      the scope of work reviewed and the 'level' at which review is approached; general
      principles for the organization of ethical review processes; the factors
      considered in the review; needs for ongoing review after initial authorization;
      participants in the review process; wider impacts of the review process; and
      strategies that can help to ensure quality and consistency of review outcomes.
      For further information and examples of current practice, as well as more
      detailed discussion to support the recommendations, readers are urged to refer to
      the complete report, available at
      http://www.lal.org.uk/pdffiles/FELASA_ethics_FULL_Report. pdf or via:
      http://www.felasa.eu/recommendations.htm.

PMID- 17430616
TI  - Influence of environmental enrichment and handling on the acute stress response
      in individually housed mice.
AB  - In this study we investigated the effect of environmental enrichment and handling
      on the acute physiological stress response caused by short periods of restraint
      in individually housed female mice. Heart rate (HR) and body temperature (BT)
      were measured by radiotelemetry and compared with plasma corticosterone (pCORT)
      levels. Also, postmortem thymus weight and tyrosine hydroxylase (TH) activity
      were assessed. The acute stress response was seen in both HR and BT. Enrichment
      and handling were found to increase rather than decrease this stress response,
      but pCORT values, measured 90 min after restraint, suggested a lower stress
      response in the enriched groups. No effect was found with thymus weight or TH as
      parameters.

PMID- 17430617
TI  - Comparative analysis and physiological impact of different tissue biopsy
      methodologies used for the genotyping of laboratory mice.
AB  - Genotyping of genetically modified mice and control of authenticity of the
      genetic background of congenic or coisogenic strains by polymerase chain reaction
      (PCR) is a routine procedure that can be performed with different tissue biopsies
      causing variable grades of trauma. In this study, some invasive and non-invasive
      sampling methods were compared, with the main focus on the impact on animal
      physiology. We compared ear punch, tail biopsy, hair plugging, mouth and rectum
      swabs and the simple restraint of the animals, scoring for the impact on heart
      rate (HR), core body temperature (BT) and motor activity by telemetry, during
      biopsy and for the following 6 h. Furthermore, in order to correlate the
      physiological impact with the practicability and reliability of the genotyping
      results, we performed a PCR analysis of the biopsy samples obtained by using the
      same collection procedures analysed by telemetry. All sampling methods and
      restraint induced significant increase in HR and BT and a slight increase in
      motor activity for 1 h, independent of the invasiveness of the method used.
      Genotyping of all biopsies allowed the proper identification of transgenic
      animals, tail biopsies, ear punches and hair follicles giving clear signals, the
      last method being fast, but also susceptible to cross contaminations during
      sampling by large numbers of animals. Restraint and all biopsy methods provoked
      similar physiological changes, indicating that the handling of the animals is of
      major importance and that the sampling procedure does not strongly influence the
      physiological parameters.

PMID- 17430614
TI  - Generation, identification and functional characterization of the nob4 mutation
      of Grm6 in the mouse.
AB  - We performed genome-wide chemical mutagenesis of C57BL/6J mice using N-ethyl-N
      nitrosourea (ENU). Electroretinographic screening of the third generation
      offspring revealed two G3 individuals from one G1 family with a normal a-wave but
      lacking the b-wave that we named nob4. The mutation was transmitted with a
      recessive mode of inheritance and mapped to chromosome 11 in a region containing
      the Grm6 gene, which encodes a metabotropic glutamate receptor protein, mGluR6.
      Sequencing confirmed a single nucleotide substitution from T to C in the Grm6
      gene. The mutation is predicted to result in substitution of Pro for Ser at
      position 185 within the extracellular, ligand-binding domain and oocytes
      expressing the homologous mutation in mGluR6 did not display robust glutamate
      induced currents. Retinal mRNA levels for Grm6 were not significantly reduced,
      but no immunoreactivity for mGluR6 protein was found. Histological and fundus
      evaluations of nob4 showed normal retinal morphology. In contrast, the mutation
      has severe consequences for visual function. In nob4 mice, fewer retinal ganglion
      cells (RGCs) responded to the onset (ON) of a bright full field stimulus. When ON
      responses could be evoked, their onset was significantly delayed. Visual acuity
      and contrast sensitivity, measured with optomotor responses, were reduced under
      both photopic and scotopic conditions. This mutant will be useful because its
      phenotype is similar to that of human patients with congenital stationary night
      blindness and will provide a tool for understanding retinal circuitry and the
      role of ganglion cell encoding of visual information.

PMID- 17430618
TI  - The antinociceptive efficacy of buprenorphine administered through the drinking
      water of rats.
AB  - Postoperative pain management in laboratory animals is important for animal
      welfare and required under law in many countries. Frequent injection of
      analgesics to rodents after surgery is stressful for the animals and labour
      intensive for animal care personnel. An alternative dosing scheme such as
      administration of analgesics in the drinking water would be desirable. However,
      the efficacy of a chronic oral analgesic treatment via this route has not yet
      been documented. This study investigated the antinociceptive efficacy of
      buprenorphine administered ad libitum via the drinking water of laboratory rats.
      The antinociceptive efficacy of buprenorphine in drinking water was compared with
      repeated subcutaneous injections. A comparison was also made between
      buprenorphine in drinking water and the combination of one single subcutaneous
      injection of buprenorphine followed by buprenorphine in drinking water.
      Antinociception was assessed by use of an analgesiometric model measuring the
      rats' latency time to withdrawal from a noxious heat stimulus applied to the
      plantar surface of the paw. Results revealed that buprenorphine in drinking water
      (0.056 mg/mL) induced significant increases in paw withdrawal latency times
      during a three-day period of administration with a maximal effect at 39 h after
      the start of buprenorphine administration. One single injection of buprenorphine
      (0.1 mg/kg s.c.) followed by buprenorphine in the drinking water (0.056 mg/mL)
      induced an earlier onset of antinociception than buprenorphine in drinking water
      alone. In contrast, buprenorphine (0.1 mg/kg s.c.) injected every 8 h over a
      period of three days did not result in significant increases in paw withdrawal
      latency times. In conclusion, our results suggest that one single subcutaneous
      injection of buprenorphine followed by buprenorphine in drinking water may be a
      viable treatment option for the relief of pain in laboratory rats, but at the
      doses used in this study in pain-free rats it was associated with a decrease in
      water intake and some behavioural changes.

PMID- 17430619
TI  - Nociception after intraperitoneal injection of a sodium pentobarbitone
      formulation with and without lidocaine in rats quantified by expression of
      neuronal c-fos in the spinal cord--a preliminary study.
AB  - After a search on Medline, it appears that intraperitoneal injection of sodium
      pentobarbitone is often used for anaesthesia and euthanasia of rodents. In the
      present pilot study in rats, spinal nociception after intraperitoneal injection
      of sodium pentobarbitone, with and without lidocaine, was examined by estimation
      of the number of c-fos-expressing neurones in the spinal dorsal horn. One group
      of rats received an intraperitoneal injection of 0.4 mL/kg sodium pentobarbitone
      (100 mg/mL; n=4). Another group of rats received a similar intraperitoneal
      injection of sodium pentobarbitone formulated with lidocaine 10 mg/mL (n=4); a
      control group received a similar intraperitoneal injection of 0.9% saline (n=4).
      After 3 h, the animals were re-anaesthetized and perfused with 4% formaldehyde,
      and the spinal cord was collected and processed by immunohistochemistry for
      stereological quantification of the number of neurones with c-fos-like
      immunoreactivity (FLI). Intraperitoneal injection of the sodium pentobarbitone
      formulation caused a significantly increased number of neurones with FLI in the
      spinal cord (3930+/-247; mean+/-SEM; P<0.001) compared with the saline control
      group (765+/-131). The lidocaine added to the sodium pentobarbitone formulation
      significantly reduced the number to 2716+/-393 (P<0.05). In conclusion,
      intraperitoneal injection of sodium pentobarbitone caused a significant increase
      in nociception which was lowered by adding lidocaine to the formulation, although
      it was still significantly higher than the control level. Further studies are
      needed with the aim of optimizing the lidocaine concentration and also to examine
      the effect of the combination of lidocaine with a long-acting local anaesthetic
      agent, e.g. bupivacaine.

PMID- 17430620
TI  - Quantitative relationship between plasma potassium levels and QT interval in
      beagle dogs.
AB  - The aim of the current study was to establish the quantitative relationship
      between plasma potassium concentrations and the QT interval of the
      electrocardiogram in dogs. Furosemide, a potent diuretic, was given at increasing
      doses (5-60 mg/kg) to five male and five female beagle dogs. Electrocardiogram
      (ECG) was recorded three times each day, simultaneous to blood sampling for
      measurement of plasma potassium. Furosemide treatment produced a clear
      hypokalaemia, which was associated with an increase in QT and corrected QT
      intervals (QTc) duration. On average, the slopes of the negative linear
      correlation between potassium plasma levels and QT or QTc were steeper in females
      than in males. These results show that a decrease in potassium plasma level may
      explain a concomitant increase in QT duration in a toxicity study in dogs, in
      particular if potassium values are decreased below 3.3 mmol/L. Correction of QT
      interval for K+ plasma level has, therefore, been established separately for
      males and females. A global formula correcting QT for K+ and heart rate
      simultaneously was established. Hypokalaemia was also associated with changes in
      the morphology of the T wave recorded in CV5RL, in particular, with a flattening
      and/or a notching of the wave (appearance of a second peak), biphasic aspect or
      inversion of polarity. These changes are probably related to an increased
      heterogeneity of repolarization between different populations of cardiomyocytes.
      In conclusion, hypokalaemia is quantitatively associated with an increase in QT
      and QTc duration in dogs. The relationship is apparently stronger for females
      than for males. A formula may be used to correct QT for potassium plasma level.

PMID- 17430621
TI  - Identification of a genetic contamination in a commercial mouse strain using two
      panels of polymorphic markers.
AB  - Rapid detection of genetic contamination is critical in mouse studies involving
      inbred strains. During a Quantitative Trait Locus (QTL) study using simple
      sequence length polymorphism (SSLP) markers, we noticed heterozygosity at some
      loci of a commercially available inbred C57BL/6N mouse strain, suggesting a
      contamination by another mouse strain. A panel of 100 single-nucleotide
      polymorphism (SNP) markers was used to confirm and specify the genetic
      contamination suspected. Retrospective analyses demonstrated that the
      contamination took place as early as autumn 2003 and has persisted ever since at
      a fairly constant level. Contaminating alleles most probably originated from a
      DBA strain. Our data demonstrate the suitability of SNP markers for rapid
      detection and identification of the source of genetic contamination. Further, our
      results show the importance of a state-of-the-art genetic monitoring of the
      authenticity of murine inbred strains.

PMID- 17430622
TI  - Serological survey of virus infection among wild house mice (Mus domesticus) in
      the UK.
AB  - The serological prevalence of 13 murine viruses was surveyed among 103 wild
      caught and 51 captive-bred house mice (Mus domesticus), originating from several
      trapping locations in northwest England, using blood samples obtained during
      routine health screening of an established wild mouse colony. A high proportion
      of recently caught wild mice were seropositive for mouse hepatitis virus (86%),
      mouse cytomegalovirus (79%), mouse thymic virus (78%), mouse adenovirus (68%),
      mouse parvovirus (59%) and minute virus of mice (41%). Seroprevalences of
      lymphocytic choriomeningitis virus (LCMV), orthopoxvirus, reovirus-3 and murid
      herpesvirus 4 (MuHV-4, also called murine gamma-herpesvirus [MHV-68]) were low (3
      13%), and no animals were seropositive to Sendai virus, pneumonia virus or
      polyomavirus. Seroprevalence in wild-caught animals that had been in captivity
      for over six months was generally consistent with the range found in recently
      caught wild animals, while seroprevalence was generally much lower in captive
      bred mice despite no attempt to prevent viral spread. A notable exception to this
      was LCMV, which appeared to have spread efficiently through the captive
      population (both captive-bred and wild-caught animals). Given the known viral
      life cycles in laboratory mice, it appears that viral persistence in the host was
      an important contributing factor in the spread of infection in captivity.

PMID- 17430623
TI  - Morphological and functional evaluation of angiogenesis of a xenografted human
      sarcoma in nude mice.
AB  - The implantation of tumour cells in normal tissues and the subsequent induction
      of angiogenesis by the growing xenograft were studied by means of
      immunohistochemistry and digital image analysis. Tumour growth was induced by
      injection of a human spindle cell sarcoma (ES3) into the subcutis of HsdCpb:NMRI
      nu/nu mice. In vivo injection of Hoechst 33342 was used as a marker of perfusion.
      The vasculature was stained with specific antibodies and subsequently analysed by
      digital image analysis. Starting at day 3 up to day 6, angiogenesis could be
      detected and the relative amount of perfusion within the investigated area
      reached a peak at day 6. This method, which allows investigation of both
      functional and morphometric characteristics of human xenograft vasculature,
      serves as an excellent assay for evaluation of antiangiogenic therapies in
      translational research of experimental tumours.

PMID- 17430624
TI  - Cryopreservation and orthotopic transplantation of rat ovaries as a means of
      gamete banking.
AB  - Besides the exponentially increasing number of mouse strains, the rising number
      of rat strains, due to the establishment of transgenic and coisogenic strains in
      this species, surpasses the capacity of most animal houses. Cryopreservation of
      gametes may be a means of solving these problems. Here we describe an easy and
      fast method for the cryopreservation and transplantation of frozen-thawed ovaries
      of the rat. Ovaries of the rat inbred strain WKY/Ztm were frozen with
      dimethylsulphoxide as cryoprotectant and stored at -196 degrees C. Orthotopical
      transplantation was performed into ovariectomized syngenic recipients. Re
      establishment of the reproductive cycle in the recipients was confirmed by
      vaginal cytology. The morphological integrity of frozen and unfrozen ovaries was
      compared by histological means after staining with haematoxylin and eosin. The
      number of litters and offspring was recorded. Reproductive cycle was re
      established in all recipients of unfrozen ovaries and in more than 50% of
      recipients that received frozen-thawed ovaries. One-third of the former and more
      than 25% of the latter became pregnant and delivered at least one litter.
      Cyropreservation of ovaries can thus be considered as a reliable method of
      preserving scientifically and economically important mutant stock, as well as
      congenic rat strains that are currently not required.

PMID- 17430625
TI  - Acclimatization of rats after ground transportation to a new animal facility.
AB  - This study aimed to assess the time needed by rats, which had not been previously
      transported, to acclimate to a new environment after 5 h of van transport, using
      physiological parameters as measures of acclimatization. Animal shipping boxes
      and transport van conditions were standardized to minimize stress factors that
      could be associated with transport. Heart rate (HR), body temperature and
      activity levels were measured in the rats before and after transport using
      previously implanted radio-telemetry transmitters. Body weight was also recorded.
      All parameters were changed significantly except for body temperature. Results
      suggest that rats take three days to acclimate to a new environment, as measured
      by the physiological parameters of body weight, HR and activity.

PMID- 17430626
TI  - Intraperitoneal versus subcutaneous telemetry devices in young Mongolian gerbils
      (Meriones unguiculatus).
AB  - Radiotelemetry has become a very popular biotelemetric tool for measuring
      physiological parameters such as heart rate, blood pressure, body temperature and
      muscle activity, as well as general behavioural activity in undisturbed, freely
      moving animals. In most studies using this technique, adult subjects are used.
      However, sometimes an ontogenetic approach is required to clarify whether changes
      in one parameter are preceeded or followed by changes in another parameter.
      Tracking physiological changes in young, developing individuals could explain
      given states of these animals as adults. Implanting telemetry devices can be done
      subcutaneously and intraperitoneally, the former method posing less of a
      challenge on the animal and its recovery from surgery. Because telemetry will be
      used in weanling gerbils during subsequent studies, we needed to investigate
      whether subcutaneous implantation of telemetric devices is preferable to
      intraperitoneal surgery with respect to animal welfare. This is a technical paper
      describing anaesthetic and surgical techniques in detail during a pre-trial
      involving subcutaneous (n=10, aged 21-29 days) and intraperitoneal (n=10, aged 19
      34 days) implantation of dummy telemetry transmitters (1.9 cm3, 3.6 g after
      shortening of leads) in weanling gerbils, Meriones unguiculatus. Body weight was
      measured and analysed over four-day intervals. Optimizing anaesthetic dosages was
      a first step in this pilot trial. This occurred during the first few subcutaneous
      implantations. Three animals died while anaesthetized during the subcutaneous
      procedure but none post-surgery. All animals survived anaesthesia during the
      intraperitoneal implantation, but two died in the first three days post-surgery.
      In the former method, the tension on the dermal sutures caused by the presence of
      the transmitters was too great, resulting in the animals opening the sutures by
      chewing them. The animals died during the latter procedure probably due to
      strangulation of the intestine by the excess lead that was coiled in the abdomen.
      Furthermore, placement of the exposed negative lead of the transmitter on the
      underlying muscle had to be done on the m. pectoralis transversus in order for it
      to stay in place as the animal developed. This paper showed that the implantation
      of a telemetric device in weanling gerbils is feasible and is best executed
      through the intraperitoneal technique.

PMID- 17430627
TI  - The Saanen goat as an animal model for post-laryngectomy research: practical
      implications.
AB  - A modern way of voice rehabilitation after total laryngectomy includes the use of
      shunt valves and tracheostoma valves. Problems of fixation to the surrounding
      tissue are a major drawback in the use of the shunt valve, heat and moisture
      exchange (HME) filters and, especially, the tracheostoma valve. To solve these
      problems different tissue connectors were developed. The main objective was to
      test the feasibility of these prototypes in a new animal model. Here we discuss
      the results, problems and complications of the selected Saanen goat model. In
      this prospective laboratory study, 19 healthy adult female Saanen goats (Capra
      hircus) were used and observed post-surgically for 12 weeks. Selection criteria
      such as comparable anatomy to humans and easy handling were used for animal model
      development. Also a literature search using the Medline and the ISI Web of
      Science databases was performed. The anatomy of the Saanen goat was investigated
      in a separate postmortem study. Surgery consisted of a laryngotracheal separation
      and implantation of a tracheo-oesophageal and tracheostoma tissue connector with
      fibrin tissue glue. Postoperative care consisted of frequent stoma care,
      monitoring appetite, weight, vital signs and administration of antibiotics,
      analgesics and mucolytic agents. All animals survived the surgical procedure.
      However, postoperative care was extensive, labour intensive and was accompanied
      by several complications. Eleven animals died spontaneously before the end of the
      experiment. The tracheostoma tissue connector caused signs of local infection in
      all cases. There was no evidence of infection around the tracheo-oesophageal
      tissue connector in 18 cases. It was concluded that the use of goats in this
      tracheostoma model was associated with major complications and should, therefore,
      only be used for short-term experiments with intensive care. Additional research
      is needed to see if clinical application of the tissue connectors is possible in
      the future.

PMID- 17430628
TI  - Ultrastructural characteristics of the external surfaces of Pasteurella
      pneumotropica from mice and Pasteurella multocida from rabbits.
AB  - The surface structures of the cells of Pasteurella pneumotropica from mice and
      Pasteurella multocida from rabbits were examined by transmission electron
      microscopy after ruthenium red staining and polycationic ferritin labelling. P.
      pneumotropica strains ATCC 35149 and K 79114 had slight extracellular fibrous
      materials associated with cell walls with ruthenium red staining. Ferritin
      labelling method revealed thick strands or sparsely ferritin-labelled materials
      on the cell surface of the strains. P. multocida strains Pm-78 and P-2440 had
      ferritin-labelled capsules surrounded with the cell wall. Strain Pm-78, which was
      serotyped as A:12, had a thick capsule, whereas serotype -:3 strain P-2440 had a
      thin and irregular capsule.

PMID- 17430629
TI  - Isolation of the mite Myocoptes musculinus Koch from the Spinifex Hopping mouse
      (Notomys alexis).
AB  - This paper reports on the isolation and identification of the fur-clasping mite,
      Myocoptes musculinus, from the faeces of the Spinifex Hopping mouse (Notomys
      alexis). This investigation adds to the sparse records of ectoparasites collected
      from native Australian murids.

PMID- 17430630
TI  - pH-sensitive liposomes--principle and application in cancer therapy.
AB  - The purpose of this review is to provide an insight into the different aspects of
      pH-sensitive liposomes. The review consists of 6 parts: the first introduces
      different types of medications made in liposomal drug delivery to overcome
      several drawbacks; the second elaborates the development of pH-sensitive
      liposomes; the third explains diverse mechanisms associated with the endocytosis
      and the cytosolic delivery of the drugs through pH-sensitive liposomes; the
      fourth describes the role and importance of pH-sensitive lipid
      dioleoylphosphatidylethanolamine (DOPE) and research carried on it; the fifth
      explains successful strategies used so far using the mechanism of pH sensitivity
      for fusogenic activity; the final part is a compilation of research that has
      played a significant role in emphasizing the success of pH-sensitive liposomes as
      an efficient drug delivery system in the treatment of malignant tumours. pH
      Sensitive liposomes have been extensively studied in recent years as an amicable
      alternative to conventional liposomes in effectively targeting and accumulating
      anti-cancer drugs in tumours. This research suggests that pH-sensitive liposomes
      are more efficient in delivering anti-cancer drugs than conventional and long
      circulating liposomes due to their fusogenic property. Research focused on the
      clinical and therapeutic side of pH-sensitive liposomes would enable their
      commercial utility in cancer treatment.

PMID- 17430631
TI  - Synthesis and evaluation of ampicillin-conjugated gum arabic microspheres for
      sustained release.
AB  - Ampicillin was conjugated to periodate-oxidized gum arabic (GA), a branched
      polysaccharide, to form the imino conjugate of the drug and the polysaccharide.
      The water-soluble conjugate was dispersed by sonication in a mixture of toluene
      and liquid paraffin in the presence of a non-ionic surfactant as droplet
      stabilizer and fabricated into microspheres by heat denaturation at 80 degrees C
      to obtain spheres less than 2 microm in diameter. These microspheres did not
      undergo dissolution in water on prolonged incubation. In-vitro release of
      ampicillin into phosphate buffer from the microspheres was slow and sustained
      with a cumulative release between 10 and 25% of the drug content in 10 days
      depending on the degree of oxidation of GA and the drug payload. Release into
      simulated gastric fluid was faster due to faster hydrolysis of the drug-GA bond
      in the acid medium, but when the medium was changed to intestinal fluid, the
      release was slowed down. Ampicillin released was functionally active and
      inhibited the growth of S. aureus and E. coli in cultures, although not as
      actively as free ampicillin. The microspheres underwent slow biodegradation on
      prolonged incubation in aqueous media. These studies show that ampicillin
      conjugated with oxidized GA and fabricated into microspheres possesses sustained
      release characteristics for prolonged periods.

PMID- 17430632
TI  - Pharmacokinetic modelling of pentoxifylline and lisofylline after oral and
      intravenous administration in mice.
AB  - The aim of this study was to develop pharmacokinetic models for pentoxifylline
      (PTX) and the R(-)-enantiomer of the PTX metabolite 1, lisofylline (LSF), in
      order to identify some factors influencing the absorption of these compounds from
      the intestines and to clarify mechanisms involved in their non-linear
      pharmacokinetics. Serum samples were collected after oral and intravenous
      administration of PTX and LSF to male CD-1 mice at two different doses. In
      addition, both compounds under investigation were coadministered with a modulator
      of drug transporters, verapamil, and an inhibitor of cytochrome P450 (CYP) 3A4,
      ketoconazole. Pharmacokinetic analysis revealed that a one-compartment model with
      Michaelis-Menten type absorption and elimination best described the
      pharmacokinetics of PTX, whereas the LSF concentration-time data were adequately
      fitted to a two-compartment model with a first-order absorption and Michaelis
      Menten type elimination process. Both coadministered compounds significantly
      decreased the area under the concentration-time curve from 0 to 60 min calculated
      for PTX and increased the value of this parameter for LSF. The results of this
      study indirectly suggest that saturation of drug transport across intestinal
      cells and elimination from the central compartment may be responsible for the non
      linear pharmacokinetics of PTX, whereas in the case of LSF, the dose dependency
      in the pharmacokinetics is solely related to the elimination from the central
      compartment. It seems that the observed changes in PTX and LSF concentrations
      after coadministration with verapamil and ketoconazole may be clinically
      significant, especially after chronic treatment, however further studies are
      necessary to assess the importance of these interactions in humans.

PMID- 17430633
TI  - Transport and metabolism of MitoQ10, a mitochondria-targeted antioxidant, in Caco
      2 cell monolayers.
AB  - Mitoquinone (MitoQ(10) mesylate) is a mitochondria-targeted antioxidant
      formulated for oral administration in the treatment of neurodegenerative
      diseases. We have investigated the absorption and metabolism of MitoQ(10) in Caco
      2 cell monolayers. The intracellular accumulation of MitoQ(10) was 18-41% of the
      total amount of MitoQ(10) added. Some of the intracellular MitoQ(10) was reduced
      to mitoquinol and subsequently metabolized to glucuronide and sulfate conjugates.
      Transport of MitoQ(10) was polarized with the apparent permeability (P(app)) from
      basolateral (BL) to apical (AP) (P(appBL-->AP)) being >2.5-fold the P(app) from
      apical to basolateral (P(appAP-->BL)). In the presence of 4% bovine serum albumin
      on the basolateral side, the P(appAP-->BL) value increased 7-fold compared with
      control. The P(appBL-->AP) value decreased by 26, 31 and 61% in the presence of
      verapamil 100 microM, ciclosporin 10 and 30 microM, respectively, whereas the
      P(appAP-->BL) value increased 71% in the presence of ciclosporin 30 microM.
      Apical efflux of mitoquinol sulfate and mitoquinol glucuronide conjugates was
      significantly decreased by ciclosporin 30 microM and the breast cancer receptor
      protein (BCRP) inhibitor, reserpine 25 microM, respectively. These results
      suggested that the bioavailability of MitoQ(10) may be limited by intracellular
      metabolism and the action of P-glycoprotein and BCRP. However, the dramatic
      increase in absorptive P(app) in the presence of bovine serum albumin on the
      receiver side suggests these barrier functions may be less significant in-vivo.

PMID- 17430634
TI  - Site-specific bidirectional efflux of 2,4-dinitrophenyl-S-glutathione, a
      substrate of multidrug resistance-associated proteins, in rat intestine and Caco
      2 cells.
AB  - The site-specific function of multidrug-resistance-associated proteins (MRPs),
      especially MRP2 and MRP3, was examined in rat intestine and human colon
      adenocarcinoma (Caco-2) cells. The MRP function was evaluated pharmacokinetically
      by measuring the efflux transport of 2,4-dinitrophenyl-S-glutathione (DNP-SG), an
      MRP substrate, after application of 1-chloro-2,4-dinitrobenzene (CDNB), a
      precursor of DNP-SG. The expression of rat and human MRP2 and MRP3 was analysed
      by Western blotting. The rat jejunum exhibited a higher apical MRP2 and a lower
      basolateral MRP3 expression than ileum. In accordance with the expression level,
      DNP-SG efflux to the mucosal surface was significantly greater in jejunum, while
      serosal efflux was greater in ileum. Site-specific bidirectional efflux of DNP-SG
      was also observed in in-vivo studies, in which portal and femoral plasma levels
      and biliary excretion rate of DNP-SG were significantly higher when CDNB was
      administered to ileum. Caco-2 cells also showed a bidirectional efflux of DNP-SG.
      Probenecid, an MRP inhibitor, significantly suppressed the mucosal efflux in
      jejunum and serosal efflux in ileum. In contrast, probenecid significantly
      suppressed both apical and basolateral efflux of DNP-SG in Caco2 cells, though
      the inhibition was of small magnitude. In conclusion, the efflux of DNP-SG from
      enterocytes mediated by MRPs exhibited a significant regional difference in rat
      intestine, indicating possible variability in intestinal bioavailabilities of MRP
      substrates, depending on their absorption sites along the intestine.

PMID- 17430635
TI  - Protective action of 9-hydroxypinoresinol against oxidative damage in brain of
      mice challenged with kainic acid.
AB  - The neuroprotective effect of 9-hydroxypinoresinol was examined in mice
      challenged with kainic acid (KA), a potent central nervous system excitotoxin.
      For this purpose, mice were administered intraperitoneally with 9
      hydroxypinoresinol before KA injection. A remarkable neuroprotective effect was
      observed with a single dose of 9-hydroxypinoresinol (30 mg kg(-1)) 24 h before KA
      challenge. Furthermore, 9-hydroxypinoresinol (20 mg kg(-1)) administered for 3
      days before KA challenge reduced the mortality (60%) induced by KA to zero, and
      alleviated behavioural signs of KA neurotoxicity. Additionally, pretreatment with
      9-hydroxypinoresinol (20 mg kg(-1)) prevented the decrease in the levels of total
      glutathione (GSH) and thiobarbituric acid reactive substances (P < 0.05). GSH
      peroxidase activity in brain tissue was restored to control levels, although GSH
      reductase activity and GSH S-transferase activity were not affected. Such a
      protective action was also observed even with a lower dose (10 mg kg(-1)) of 9
      hydroxypinoresinol administered for 3 days, albeit to a lesser extent. From the
      results, it is proposed that 9-hydroxypinoresinol exerts a potent neuroprotective
      effect mainly by preventing oxidative stress in brain tissue of mice challenged
      with KA.

PMID- 17430636
TI  - Amides from Piper nigrum L. with dissimilar effects on melanocyte proliferation
      in-vitro.
AB  - Melanocyte proliferation stimulants are of interest as potential treatments for
      the depigmentary skin disorder, vitiligo. Piper nigrum L. (Piperaceae) fruit
      (black pepper) water extract and its main alkaloid, piperine (1), promote
      melanocyte proliferation in-vitro. A crude chloroform extract of P. nigrum
      containing piperine was more stimulatory than an equivalent concentration of the
      pure compound, suggesting the presence of other active components. Piperine (1),
      guineensine (2), pipericide (3), N-feruloyltyramine (4) and N-isobutyl-2E, 4E
      dodecadienamide (5) were isolated from the chloroform extract. Their activity was
      compared with piperine and with commercial piperlongumine (6) and safrole (7),
      and synthetically prepared piperettine (8), piperlonguminine (9) and 1-(3, 4
      methylenedioxyphenyl)-decane (10). Compounds 6-10 either occur in P. nigrum or
      are structurally related. Compounds 1, 2, 3, 8 and 9 stimulated melanocyte
      proliferation, whereas 4, 5, 6, 7 and 10 did not. Comparison of structures
      suggests that the methylenedioxyphenyl function is essential for melanocyte
      stimulatory activity. Only those compounds also possessing an amide group were
      active, although the amino component of the amide group and chain linking it to
      the methylenedioxyphenyl group can vary. P. nigrum, therefore, contains several
      amides with the ability to stimulate melanocyte proliferation. This finding
      supports the traditional use of P. nigrum extracts in vitiligo and provides new
      lead compounds for drug development for this disease.

PMID- 17430637
TI  - Design, synthesis and enzymatic evaluation of 6-bridged imidazolyluracil
      derivatives as inhibitors of human thymidine phosphorylase.
AB  - A series of novel imidazolyluracil conjugates were rationally designed and
      synthesised to probe the active site constraints of the angiogenic enzyme,
      thymidine phosphorylase (TP, E.C. 2.4.2.4). The lead compound in the series, 15d,
      showed good binding in the active site of human TP with an inhibition in the low
      muM range. The absence of a methylene bridge between the uracil and the
      imidazolyl subunits (series 16) decreased potency (up to 3-fold). Modelling
      suggested that active site residues Arg202, Ser217 and His116 are important for
      inhibitor binding.

PMID- 17430638
TI  - Hypothermic effects of hops are antagonized with the competitive melatonin
      receptor antagonist luzindole in mice.
AB  - Hops (Humulus lupulus, Cannabinaceae) has been used in traditional European
      medicine as a mild sedative for the treatment of anxiety, nervousness, and
      insomnia. However, there has been little information available about the
      underlying sleep inducing mechanism of hops. We have investigated the effects of
      a hops extract on the rectal body temperature in mice. Hops extract (250 mg kg(
      1)) significantly decreased body temperature in male BL6/C57J mice (DeltaT -0.75
      +/- 0.07 degrees C) 2 h after oral administration. The effects of the plant
      extract were comparable with melatonin (50 mg kg(-1); DeltaT -0.66 +/- 0.06
      degrees C; 2 h after i.p. injection). The hypothermic effects of melatonin and
      hops extract were antagonized with the competitive melatonin receptor antagonist
      luzindole. Thus, our data suggests that the hypothermic--and therefore the sleep
      inducing--effects of hops extract are possibly mediated through activation of
      melatonin receptors.

PMID- 17430639
TI  - Antioxidant and anticancer activity of 3'-formyl-4', 6'-dihydroxy-2'-methoxy-5'
      methylchalcone and (2S)-8-formyl-5-hydroxy-7-methoxy-6-methylflavanone.
AB  - Two new flavonoids - 3'-formyl-4',6'-dihydroxy-2'-methoxy-5'-methylchalcone (FMC)
      and (2S)-8-formyl-5-hydroxy-7-methoxy-6-methylflavanone (FMF) - isolated from the
      buds of Cleistocalyx operculatus, were investigated for their antioxidant and
      anticancer activity. Total antioxidant activity and reducing ability were
      measured. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and superoxide anion
      radical scavenging assays were carried out to evaluate the antioxidant potential
      of the two compounds. The antioxidant activity of the two compounds increased in
      a concentration-dependent manner. FMC and FMF at a concentration of 500 microM
      inhibited lipid peroxidation by 64.3 +/- 2.5% and 60.3 +/- 2.3%, respectively, an
      antioxidant activity approximately similar to that of 500 microM alpha-tocopherol
      (66.3 +/- 2.5%). Similarly, the effect of FMC and FMF on reducing power increased
      in a concentration-dependent manner. In DPPH radical scavenging assays, the IC50
      values of FMC and FMF were 50.2 +/- 2.8 microM and 75.8 +/- 2.5 microM,
      respectively. Moreover, FMC and FMF scavenged the superoxide generated by the
      phenazine methosulfate (PMS)/reduced beta-nicotinamide adenine dinucleotide
      (NADH) nitroblue tetrazolium (NBT) system, with IC50 values of 56.3 +/- 2.3
      microM and 317.5 +/- 2.9 microM, respectively. The anticancer activity of the two
      compounds were determined in five human cancer cell lines, SMMC-7721 (liver
      cancer), 8898 (pancreatic cancer), K562 (chronic leukaemia), HeLa (tumour of
      cervix uteri) and 95-D (high metastic lung carcinoma). FMC and FMF showed broad
      spectrum anticancer activity against all the human cancer cell lines tested. The
      results obtained in the current study indicate that the two flavonoids could be a
      potential source of natural antioxidant and anticancer agents. To our knowledge,
      this is the first report on bioactivity of FMC and FMF.

PMID- 17430640
TI  - Suppression of the NF-kappaB signalling pathway by ergolide, sesquiterpene
      lactone, in HeLa cells.
AB  - We have previously reported that ergolide, a sesquiterpene lactone isolated from
      Inula britannica, suppresses inducible nitric oxide synthase (iNOS) and
      cyclooxygenase-2 (COX-2) expression by inhibiting nuclear factor-kappaB (NF
      kappaB) in RAW 264.7 macrophages. In this study, we show that ergolide suppresses
      the DNA binding activity of NF-kappaB and nuclear translocation of NF-kappaB p65
      subunit, leading to the inhibition of NF-kappaB-dependent gene transcription in
      12-O-tetradecanoylphorbol 13acetate (TPA)-stimulated HeLa cells. We also show
      that ergolide decreases the degradation and phosphorylation of IkappaB, an
      inhibitory protein of NF-kappaB, and this effect is accompanied by a simultaneous
      reduction of IkappaB kinase (IKK) activity. However, ergolide does not inhibit in
      vitro IKK activity directly, suggesting the possible involvement of upstream IKK
      kinases in the regulation of NF-kappaB activation. Furthermore, ergolide-mediated
      protein kinase Calpha (PKCalpha) inhibition is involved in reduction of NF-kappaB
      inhibition, as demonstrated by the observation that dominant negative PKCalpha,
      but not p44/42 MAPK and p38 MAPK, inhibits TPA-stimulated reporter gene
      expression. Taken together, our results suggest that ergolide suppresses NF
      kappaB activation through the inhibition of PKCalpha-IKK activity, providing
      insight for PKCalpha as a molecular target for anti-inflammatory drugs.

PMID- 17430641
TI  - Cytochrome P450 inhibitory action of Echinacea preparations differs widely and co
      varies with alkylamide content.
AB  - Echinacea preparations are one of the best selling herbal medicinal products with
      a well established therapeutic use in the prophylaxis of upper respiratory tract
      infections. Their consumption is increasing, but information about their ability
      to inhibit cytochrome P450 enzymes (CYP) is fragmentary. The picture is further
      complicated by a lack of phytochemical characterization of previously tested
      preparations. Due to its well characterized immunomodulatory activity, the
      standardized Swiss registered Echinacea purpurea (L.) Moench Echinaforce extract
      was selected for detailed study. With the single baculovirus-expressed CYP
      isoforms 1A2, 2C19, 2D9 and 3A4, inhibitory actions were measured by monitoring
      fluorescent metabolites derived from enzyme substrates (supersome assay). The
      Echinaforce extract induced mild inhibition of all these isoforms, with CYP 3A4
      being the most, and CYP 2D6 the least sensitive enzyme. To assess whether CYP
      inhibition might be a general feature of Echinacea preparations, an additional
      nine commercially available preparations were screened using CYP 3A4. All tested
      preparations were able to inhibit CYP 3A4, but inhibitory potencies (expressed as
      median inhibitory concentration, IC50) varied by a factor of 150. The alkylamides
      are thought to be responsible for the immunomodulatory activity of Echinacea, and
      so the concentration of 2E,4E,8Z,10E/Z-tetranoic acid isobutylamide (1) and total
      alkylamide content were determined in all preparations, and the latter was found
      to be associated with their CYP 3A4 inhibitory potency. The chemically pure
      alkylamides dodeca-2E,4E,8Z,10E/Z-tetranoic acid isobutylamide (1) and dodeca
      2E,4E-dieonoic acid isobutylamide (2) showed inhibitory activity on CYP 2C19, 2D6
      and 3A4. However, unlike the Echinaforce extract, the alkylamides did not induce
      CYP 1A2 inhibition. Thus, other, as yet unidentified constituents also contribute
      to the overall weak inhibitory effects seen with Echinacea preparations in-vitro.

PMID- 17430642
TI  - Anti-diabetic effect of an alpha-glucan from fruit body of maitake (Grifola
      frondosa) on KK-Ay mice.
AB  - We have evaluated the anti-diabetic effect of a alpha-glucan (MT-alpha-glucan)
      from the fruit body of maitake mushrooms (Grifola frondosa) on KK-Ay mice (a kind
      of genetical type 2 diabetes animal model). The effects of MT-alpha-glucan (450
      or 150 mg kg (-1)) on diabetic mice were investigated by observing the changes in
      body weight, the level of fasting plasma glucose, glycosylated serum protein
      (GSP), hepatic glycogen, serum insulin, triglycerides, cholesterol, free fatty
      acid, liver superoxide dismutase (SOD), glutathione peroxidase (GSHpx), reduced
      glutathione (GSH) and malondialdehyde (MDA). Moreover, the binding capacity of
      insulin receptors on liver crude plasma membranes was assayed and
      histopathological changes in the pancreas were observed. Treatment with MT-alpha
      glucan significantly decreased the body weight, level of fasting plasma glucose,
      GSP, serum insulin, triglycerides, cholesterol, free fatty acid and MDA content
      in livers. Treatment with MT-alpha-glucan significantly increased the content of
      hepatic glycogen, GSH and the activity of SOD and GSHpx. Moreover, the insulin
      binding capacity to liver crude plasma membranes increased and histopathological
      changes in the pancreas were ameliorated in the treatment group. These data
      suggest that MT-alpha-glucan has an anti-diabetic effect on KK-Ay mice, which
      might be related to its effect on insulin receptors (i.e., increasing insulin
      sensitivity and ameliorating insulin resistance of peripheral target tissues).

PMID- 17430643
TI  - Yin-Chen-Hao-Tang ameliorates obstruction-induced hepatic apoptosis in rats.
AB  - The accumulation of hydrophobic bile acids in the liver is considered to play a
      pivotal role in the induction of apoptosis of hepatocytes during cholestasis.
      Thus, factors that affect apoptosis may be used to modulate liver fibrosis. Yin
      Chen-Hao-Tang (YCHT) decoctions have been recognised as a hepatoprotective agent
      for jaundice and various types of liver diseases. We used an experimental rat
      model of bile-duct ligation (BDL) to test whether YCHT plays a regulatory role in
      the pathogenesis of hepatic apoptosis. BDL-plus-YCHT groups received 250 or 500
      mg kg (-1) YCHT by gavage once daily for 27 days. YCHT significantly ameliorated
      the portal hypertensive state and serum TNF-alpha compared with the vehicle
      treated control group. In BDL-plus-YCHT-treated rats, hepatic glutathione
      contents were significantly higher than than in BDL-only rats. BDL caused a
      prominent liver apoptosis that was supported by an increase in Bax and cytochrome
      c protein and increased expression of Bax and Bcl-2 messenger RNA. The
      normalising effect of YCHT on expression of Bax and Bcl-2 mRNA was dependent on
      the dose of YCHT, 500 mg kg (-1) having the greater effect on both Bax and Bcl-2
      of mRNA levels. Additionally, YCHT treatment down-regulated both hepatic caspase
      3 and -8 activities of BDL rats. This study demonstrates the anti-apoptotic
      properties of YCHT and suggests a potential application of YCHT in the clinical
      management of hepatic disease resulting from biliary obstruction.

PMID- 17430644
TI  - Anti-inflammatory and antinociceptive properties of blueberry extract (Vaccinium
      corymbosum).
AB  - Blueberries are among the edible fruits that are recognized best for their
      potential health benefits. The crude extract from Vaccinium corymbosum was
      assessed in anti-inflammatory and antinociceptive models. The crude
      hydroalcoholic extract was administered orally at doses of 100, 200 or 300 mg kg
      (-1) for all the assays. In the carrageenan test, the crude extract reduced rat
      paw oedema by 9.8, 28.5 and 65.9%, respectively. For the histamine assay, the
      reductions of oedema were 70.1, 71.7 and 81.9%, respectively. In the
      myeloperoxidase (MPO) assay, 300 mg kg (-1) crude extract produced a significant
      inhibition of the MPO activity, at 6 h and 24 h after injection of carrageenan,
      by 42.8 and 46.2%, respectively. With the granulomatous tissue assay
      dexamethasone displayed significant activity, whereas the blueberry extract was
      inactive. For the abdominal constriction test, inhibitions of 49.0, 54.5, 53.5%,
      respectively, were observed for the crude extract, and 61.4% for indometacin. In
      the formalin test, the crude extract (200 and 300 mg kg (-1)) and indometacin
      inhibited only the second phase by 36.2, 35.3 and 45.8%, respectively.
      Considering that the crude extract of blueberry displayed antinociceptive and
      anti-inflammatory activity, its consumption may be helpful for the treatment of
      inflammatory disorders.

PMID- 17430645
TI  - Iron (III) chelation and antioxidant properties of myo-inositol phosphorylated
      polymeric microspheres.
AB  - New chelating and antioxidant polymeric microspheres were synthesized through
      precipitation polymerization of 4-O-(4-vinylbenzyl)-myo-inositol 1,3,5
      orthoformate with ethylene glycol dimethacrylate and subsequent exhaustive
      phosphorylation of the myo-inositol groups with phosphoric acid. Three different
      microspheres using different molar ratios of the two co-monomers were prepared.
      The antioxidant properties of these polymers were evaluated in rat liver
      microsomal membranes. This study showed that the macromolecular systems are very
      effective at inhibiting iron-dependent lipid peroxidation of the membranes. This
      antioxidant effect is due to the chelating properties of polyphosphorylated
      inositol residues in the polymeric devices toward ferric ions. The amount of
      polyphosphorylated inositol in the microspheres was found to play a crucial role
      in determining the chelating efficiency of the polymers: the polymer with the
      greatest amount of polyphosphorylated inositol was the most powerful antioxidant
      polymer.

PMID- 17430646
TI  - Baccharis dracunculifolia, the main botanical source of Brazilian green propolis,
      displays antiulcer activity.
AB  - Baccharis dracunculifolia is the most important botanical source of Southeastern
      Brazilian propolis, known as green propolis for its colour. In a previous study,
      we described the gastric protective effect of the hydroalcoholic extract of
      Brazilian green propolis. We therefore wanted to investigate the possibility of
      using B. dracunculifolia extract for antiulcer treatment. This study was
      undertaken to evaluate the anti-ulcerogenic property of hydroalcoholic extract of
      B. dracunculifolia aerial parts. The HPLC analysis of the chemical composition of
      B. dracunculifolia extract used in this study revealed the presence mainly of
      cinnamic acid derivates and flavonoids. Doses of 50, 250 and 500 mg/kg of B.
      dracunculifolia crude extract and positive controls (omeprazole or cimetidine)
      significantly diminished the lesion index, the total lesion area and the
      percentage of lesion compared with negative control groups. The percentage of
      ulcer inhibition was significantly higher in groups treated with B.
      dracunculifolia, cimetidine or omeprazole, with all protocols used, compared with
      negative control groups. Regarding the model of gastric secretion, reductions in
      the volume of gastric juice and total acidity were observed, as well as an
      increase in the gastric pH. These results were similar to results from studies
      carried out with green propolis extract. Although more investigations are
      required, our results suggest that B. dracunculifolia has potential to be used as
      a phytotherapic preparation for the treatment of gastric ulcer.

PMID- 17430647
TI  - [Development of the general module of the system of quality of life instruments
      for cancer patients: responsiveness analysis].
AB  - BACKGROUND & OBJECTIVE: The general module of the system of quality of life
      instruments for cancer patients, QLICP-GM, has been developed and its reliability
      and validity has been evaluated by us. This study was to analyze its
      responsiveness. METHODS: The quality of life of 600 patients with 5 kinds of
      cancer was measured using QLICP-GM before and after treatment. Traditional
      significance tests with some indices, such as effect size, standardized response
      mean and equivalence, were applied to evaluate responsiveness. RESULTS: The
      quality of life score changed significantly after treatment on 3 domains:
      physical function, psychologic function, and general symptoms and side effects.
      The standardized response mean of the overall instrument ranged from 0.16 to
      0.67. Equivalence test showed no equivalence on quality of life score changes of
      these domains and the overall instrument. CONCLUSION: QLICP-GM possesses
      reasonable responsiveness and can be used in clinical measurement of quality of
      life for cancer patients.

PMID- 17430648
TI  - [Establishment and application of an orthotopic murine bladder cancer model].
AB  - BACKGROUND & OBJECTIVE: The recurrence rate of superficial bladder cancer is
      still high even the patients received postoperative intravesical infusion of
      chemotherapeutic drugs, such as mitomycin C (MMC). Some studies showed that
      intravesical infusion of small interfering RNA (siRNA) could suppress the growth
      of bladder cancer in nude mice. This study was to establish an orthotopic animal
      model bearing human bladder cancer, monitor tumor progression by magnetic
      resonance imaging (MRI), and observe the synergistic effect of survivin short
      hairpin RNA (shRNA) in combination with MMC for intravesical treatment using this
      animal model. METHODS: Human bladder cancer cell line T24 was inoculated into the
      bladders of 25 BALB/c nude mice to establish orthotopic bladder cancer model. MRI
      was performed to monitor tumor progression, using Gd-DTPA as contrast agent. The
      pathologic morphology of the bladders was observed. Eighteen mice bearing bladder
      cancer were randomized into 3 groups: untreated group, MMC group, and combination
      group. The bladders were weighed after 6 intravesical infusions. RESULTS: All the
      25 mice developed bladder cancer after T24 cell inoculation. On MRI, no change in
      the bladders was observed at 7 days after inoculation, filling defect in the
      bladders, accordant to actual tumor size, was detected at 14, 21, and 28 days
      after inoculation. Pathologic examination showed that tumors grew in mucosa of
      the bladders at 7 days after inoculation, infiltrated into muscle layer at 14-28
      days after inoculation, and invaded serosa at 35 days after inoculation. The
      inhibition rate of tumor growth was significantly higher in combination group
      than in MMC group (56.34% vs. 33.45%, P<0.05). CONCLUSION: We successfully
      established an orthotopic bladder cancer model, which could simulate the
      progression of human bladder cancer approximately. MRI is a reliable way for
      dynamic detection of murine orthotopic bladder tumor. Down-regulating survivin
      expression by RNA interference could enhance the antitumor effect of MMC.

PMID- 17430649
TI  - [Efficacy of chitosan and hyaluronidase on skin damage caused by docetaxel
      extravasation in rats].
AB  - BACKGROUND & OBJECTIVE: Docetaxel extravasating into the surrounding tissues may
      lead to severe skin damage. No guideline for handling docetaxel extravasation has
      been proposed till now. This study was to explore the efficacy of chitosan and
      hyaluronidase on skin damage caused by docetaxel extravasation in a rat model.
      METHODS: A docetaxel extravasation model was established in both lower
      extremities of 30 Sprague-Dawley rats. The rats were divided into 6 groups and
      received chitosan embrocation, hyaluronidase injection, hyaluronidase injection
      plus chitosan embrocation, saline embrocation, or saline injection, or received
      no treatment as control. The occurrence rate and extent of skin damage, and the
      healing time were observed and compared. RESULTS: The occurrence rate of skin
      damage was significantly lower in hyaluronidase group and hyaluronidase plus
      chitosan group than in chitosan group, saline embrocation group, saline injection
      group, and control group (30% and 20% vs. 90%, 100%, 90% and 100%, P<0.05). The
      healing time was significantly shorter in hyaluronidase group and hyaluronidase
      plus chitosan group than in chitosan group, saline embrocation group, saline
      injection group, and control group [(12.00+/-3.00) days and (9.50+/-2.12) days
      vs. (18.33+/-2.00) days, (23.70+/-2.41) days, (18.44+/-2.01) days and (25.70+/
      2.26) days, P<0.01], and was significantly shorter in chitosan group than in
      saline embrocation group and control group (P<0.01). CONCLUSIONS: Hyaluronidase
      alone or hyaluronidase plus chitosan could decrease the occurrence rate of skin
      damage caused by docetaxel extravasation in rats, and shorten the healing time.
      Chitosan embrocation can improve the damage healing, but cannot decrease the
      occurrence rate of skin damage.

PMID- 17430650
TI  - [Effects of diallyl disulfide on differential expression of apoptosis-associated
      genes in leukemia cell line HL-60].
AB  - BACKGROUND & OBJECTIVE: Diallyl disulfide (DADS) can induce apoptosis in various
      cancer cell lines in vitro. Leukemia is the most common pediatric malignancy.
      Recent studies have suggested that DADS can induce apoptosis in human leukemia
      cells, but its mechanisms remain unclear. This study was to investigate the
      biological effects of DADS on the apoptosis of human leukemia cell line HL-60,
      and explore its molecular mechanisms. METHODS: After treatment of DADS, cell
      apoptosis was verified by flow cytometry with Annexin V/PI staining, DNA agarose
      gel electrophoresis, transmission electron microscopy. The expression profile of
      apoptosis-associated genes in HL-60 cells, with or without 4-hour treatment of
      DADS (60 micromol/L), was identified by gene array. The up-regulated Fas-L gene
      and down-regulated Bag-1 gene were confirmed by reverse transcription-polymerase
      chain reaction (RT-PCR). RESULTS: When treated with 15, 30, 60, 120 micromol/L
      DADS for 24 h, HL-60 cells presented obvious subdiploid peaks. When treated with
      60 micromol/L DADS for 4, 8, 12, 24 h, early apoptotic cells were greatly
      increased. When treated with 60 micromol/L DADS for 24 h, DNA extracted from HL
      60 cells displayed a characteristic ladder pattern on agarose gel
      electrophoresis; typical morphologic apoptotic changes were observed under
      electron microscope, including cell shrinkage, nuclear condensation, and
      formation of apoptotic bodies; the differential expression of 8 apoptosis
      associated genes were found with gene array. The expression of Fas-L and Bag-1
      detected by RT-PCR were consistent with those detected by gene array. CONCLUSION:
      DADS could induce apoptosis in HL-60 cells, which might be mediated by some
      specific genes and various signal transduction pathways.

PMID- 17430651
TI  - [Effect of neferine on adriamycin-resistance of thermotolerant hepatocarcinoma
      cell line HepG2/thermotolerance].
AB  - BACKGROUND & OBJECTIVE: Nowadays, reversing the multidrug resistance (MDR) of
      thermotolerant carcinoma cells is a hot topic in tumor thermatology. This study
      was to investigate the adriamycin (ADR)-resistance of thermotolerant
      hepatocarcinoma cell line HepG2/thermotolerance and the effect of neferine (Nef)
      on the ADR-resistance of HepG2/thermotolerance cells. METHODS: Cell proliferation
      was measured by MTT assay. Cell apoptosis was detected by flow cytometry (FCM)
      with PI staining. The expression of Bcl-2 was measured by FCM using fluorescein
      isothiocyanate (FITC)-conjugated anti-bcl-2 antibodies. RESULTS: The
      proliferation rate and apoptosis rate of HepG2/thermotolerance cells cultured in
      43 degrees C for 24 h were (89.6+/-5.4)% and (13.6+/-5.4)%, respectively;
      however, those of HepG2 cells were (23.9+/-3.6)% and (68.9+/-7.3)%, respectively.
      The 50% inhibition concentration (IC50) of ADR was 10.8 times higher for
      HepG2/thermotolerance cells than for HepG2 cells [(113.7+/-12.7) micromol/L vs.
      (10.5+/-2.3) micromol/L]. When treated with 1, 10, 100 micromol/L ADR at 37
      degrees C for 24 h, the apoptosis rates of HepG2/thermotolerance cells were
      (9.3+/-2.6)%, (17.8+/-7.3)%, and (32.9+/-8.6)%, respectively, but those of HepG2
      cells were (14.3+/-3.9)%, (38.9+/-6.8)%, and (62.7+/-5.9)%, respectively. In the
      presence of 10 and 40 micromol/L Nef, the IC50 of ADR for HepG2/thermotolerance
      cells was significantly decreased from (113.7+/-12.7) micromol/L to (63.7+/-5.6)
      micromol/L and (16.8+/-2.8) micromol/L, and the cell apoptosis induced by 10
      micromol/L ADR was significantly increased from (17.8+/-4.3)% to (26.8+/-5.9)%
      and (34.9+/-8.7)%, respectively. Bcl-2 was overexpressed in HepG2/thermotolerance
      cells, whereas it was down-regulated when the cells were treated with 40
      micromol/L Nef for 24 h. CONCLUSIONS: HepG2/thermotolerance cells are ADR
      resistant. Nef may reverse the ADR-resistance of HepG2/thermotolerance cells by
      down-regulating Bcl-2 expression.

PMID- 17430652
TI  - [Effect of norcantharidin's derivative Nd3 on proliferation of human ovarian
      cancer cell line SKOV3 and its possible mechanisms].
AB  - BACKGROUND & OBJECTIVE: Norcantharidin (NCTD), the demethylated form of
      cantharidin, can inhibit the proliferation of many kinds of cancer cells, but its
      effect is milder than those of other drugs. This study was to explore the
      inhibitory effect of Nd3, a derivative of norcantharidin, on the proliferation of
      human ovarian cancer cell line SKOV3, compare its antitumor effect with that of
      norcantharidin, and investigate its possible molecular mechanisms. METHODS: SKOV3
      cells were treated with Nd3 and norcantharidin, separately. Cell proliferation
      was evaluated by sulforhodamine B (SRB) assay. Cell cycle distribution and
      apoptosis were detected by flow cytometry. The expression of Cdc2, Cyclin B1,
      Bax, and Bcl-2 was detected by Western blot. RESULTS: When treated with 2.5, 5,
      10, 20, 30, and 40 micromol/L Nd3 for 48 h, the inhibition rates of SKOV3 cells
      were 27.3%, 34.1%, 53.3%, 64.3%, 83.3%, and 96.7%, respectively, which were
      significantly higher than that of negative control cells (P<0.001). The 50%
      inhibition concentration of Nd3 was (25.1+/-2.3) micromol/L at 24 h, (21.8+/-2.8)
      micromol/L at 36 h, and (20.4+/-3.3) micromol/L at 48 h. When treated with 10,
      20, 30, and 40 micromol/L Nd3 for 48 h, SKOV3 cells were arrested at G2/M phase
      at rates of 14.3%, 20.2%, 26.2%, and 27.9%; when treated with 30 micromol/L Nd3
      for 12, 24, 36, and 48 h, the proportions of SKOV 3 cells at G2/M phase were
      19.8%, 26.6%, 27.8%, and 32.0%. When treated with 40 micromol/L Nd3 for 48 h, the
      apoptosis rate of SKOV3 cells was significantly higher than that of control cells
      [(17.9+/-4.4)% vs. (2.5+/-2.8)%, P<0.01]. After treatment of Nd3, the expression
      of Cdc2, Cyclin B1, and Bcl-2 were down-regulated, and the expression of Bax was
      up-regulated. CONCLUSIONS: Nd3 inhibits SKOV3 cell proliferation more than
      norcantharidin does, blocks cell cycle at G2/M phase, and induces apoptosis. The
      antitumor mechanism of Nd3 is related to the changes of Cdc2, Cyclin B1, Bax, and
      Bcl-2 expression.

PMID- 17430654
TI  - [Effect of adenovirus-mediated mda-7/IL-24 gene infection on apoptosis of drug
      resistant human ovarian cancer cell lines OVCAR-3 and OVCAR-8/TR].
AB  - BACKGROUND & OBJECTIVE: Melanoma differentiation associated gene-7 (mda-7/IL-24)
      has double functions: specifically induces tumor cell apoptosis and modulates
      immune responses. Therefore, it is a strong candidate for human cancer gene
      therapy. This study was to evaluate the effect of adenovirus-mediated mda-7/IL-24
      infection on the apoptosis of drug-resistant ovarian cancer cell lines OVCAR-3
      and OVCAR-8/TR. METHODS: Adenovirus-mediated mda-7/IL-24 (Ad.mda-7/IL-24) was
      constructed using AdEasy 1 system. OVCAR-3 and OVCAR-8/TR cells were infected by
      Ad.mda-7/IL-24. The expression of MDA-7/IL-24 protein was detected by Western
      blot. Cell apoptosis was detected by flow cytometry with Hoechst33258 staining.
      Cell cycle distribution was detected by flow cytometry. RESULTS: The recombinant
      Ad.mda-7/IL-24 was confirmed by DNA sequencing and electrophoresis. The
      expression of MDA-7/IL-24 protein was detected in the cells after infection.
      Within 72 h after Ad.mda-7/IL-24 infection, the maximal apoptosis rates of OVCAR
      3 and OVCAR-8/TR cells were 14.1% and 32.4%, respectively, significantly higher
      than empty vector group and uninfected group. CONCLUSIONS: The recombinant Ad.mda
      7/IL-24 was successfully constructed. It can induce apoptosis in drug-resistant
      ovarian cancer OVCAR-3 and OVCAR-8/TR cells.

PMID- 17430653
TI  - [Induction effect of rapamycin combined paclitaxel on apoptosis of ovarian cancer
      cell lines A2780 and SKOV3 and the molecular mechanism].
AB  - BACKGROUND & OBJECTIVE: Previous researches confirmed that the mammalian target
      of rapamycin (mTOR) plays an important role in the tumorigenesis and development
      of malignant tumors. This study was to investigate the effect of rapamycin, a
      selective inhibitor of mTOR, combined paclitaxel on the apoptosis of ovarian
      cancer cell lines A2780 and SKOV3, and explore the molecular mechanism. METHODS:
      A2780 and SKOV3 cells were treated with rapamycin and (or) paclitaxel. Cell
      proliferation was assessed by MTT assay. The interaction of rapamycin and
      paclitaxel was estimated by Jin Zhengjun's method. Cell apoptosis was detected by
      flow cytometry (FCM). The expression of survivin in A2780 and SKOV3 cells was
      detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:
      When treated with rapamycin combined paclitaxel for 72 h, the proliferation
      inhibition rate was 34.9% for A2780 cells and 37.1% for SKOV3 cells, which was
      significantly higher than those of the cells treated with rapamycin or paclitaxel
      alone (P<0.01). These 2 drugs showed synergistic effect (q>1.15). The apoptosis
      of A2780 and SKOV3 cells were induced by rapamycin and paclitaxel; the apoptosis
      rate reached to the peak when the cells were treated with rapamycin combined
      paclitaxel. The expression of survivin in A2780 and SKOV3 cells was declined
      obviously after treatment of rapamycin combined paclitaxel. CONCLUSIONS:
      Rapamycin and paclitaxel could inhibit proliferation and induce apoptosis of
      A2780 and SKOV3 cells in vitro, and down-regulate the expression of survivin.
      These 2 drugs have synergistic effect on cell proliferation.

PMID- 17430655
TI  - [Effects of selective cyclooxygenase-2 inhibitor on proliferation and apoptosis
      of human bladder cancer cell line T24].
AB  - BACKGROUND & OBJECTIVE: Cyclooxygenase-2 (COX-2) is related closely to the
      tumorigenesis of bladder cancer, and COX-2 inhibitor has potential antitumor
      effect. This study was to investigate the effects of selective COX-2 inhibitors
      on the proliferation and apoptosis of human bladder cancer cell line T24.
      METHODS: The effects of selective COX-2 inhibitors SC-58125 and celecoxib, and
      nonselective COX inhibitor indomethacin on the proliferation of T24 cells were
      evaluated by MTT assay. Cell apoptosis was determined by flow cytometry (FCM),
      DNA ladder electrophoresis, and fluorescent microscopy with Hoechst33258
      staining. The expression of apoptosis-related genes Bcl-2 and Bax were analyzed
      by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Within
      concentrations of 12.5-200 micromol/L, SC-58125, celecoxib, and indomethacin
      could inhibit the proliferation of T24 cells to different extents. SC-58125
      tended to be more effective than the other two. The 50% inhibition concentration
      (IC50) of SC-58125 was determined to be 25-50 micromol/L. The apoptosis of T24
      cells was enhanced after exposure to SC-58125. When treated with 100 micromol/L
      SC-58125 for 6 and 12 h, the apoptosis rates of T24 cells were (7.95+/-1.88)% and
      (12.5+/-2.42)%, respectively, which were significantly higher than that of
      control cells (P<0.05). But the expression of Bcl-2 and Bax genes did not change.
      CONCLUSIONS: Selective COX-2 inhibitor could inhibit the proliferation and induce
      the apoptosis of T24 cells.

PMID- 17430656
TI  - [Inhibitory effect of combined bacterin on growth of sarcoma 180 in mice].
AB  - BACKGROUND & OBJECTIVE: It was reported that the symptoms of tumor patients may
      be alleviated markedly and even the tumor may be regressed completely after acute
      infection. Bacterin OK-432 has notable inhibitory effect on the growth of various
      tumors in animals. At present, OK-432 has been used in clinical immunotherapy for
      tumors with no other adverse events besides fever and leucocytosis. This study
      was to investigate the effects of combined bacterin on the serum level of
      interleukin 12(p70)[IL-12(p70)] and the growth of sarcoma 180 (S180) in mice.
      METHODS: After transplantation of S180, the mice were randomized into 5 groups,
      and received injection of Staphylococcus aureus, Salmonella typhimurium,
      Mycobacteria phlei, and combined bacterin containing the 3 bacteria strains,
      respectively, or received no treatment (blank control). The weight of S180
      xenografts, the thymus, and the spleen in mice was measured. The serum level of
      IL-12(p70) was detected by ELISA. RESULTS: The mean weight of S180 tumors was
      1.39 g in Staphylococcus aureus group, 1.50 g in Salmonella typhimurium group,
      1.36 g in Mycobacteria phlei group, 0.62 g in combined bacterin group, and 2.40 g
      in blank control group; the differences among the 5 groups were significant
      (F=66.73, P<0.001). The mean weight of S180 tumors was significantly lower in the
      4 bacterin groups than in control group, and significantly lower in combined
      bacterin group than in the 3 single bacterin groups (q test, P<0.001). The
      weights of the thymus and the spleen among the 5 groups had no significant
      difference (F=2.36, P>0.05; F=1.89, P>0.05). The inhibition rate of tumor growth
      was significantly higher in combined bacterin group than in Staphylococcus
      aureus, Salmonella typhimurium, and Mycobacteria phlei groups (74.17% vs. 42.08%,
      37.50%, and 43.33%, P<0.01). The mean serum level of IL-12(p70) was 19.44 pg/ml
      in combined bacterin group, 12.41 pg/ml in Staphylococcus aureus group, 10.35
      pg/ml in Salmonella typhimurium group, 11.68 pg/ml in Mycobacteria phlei group,
      and 4.45 pg/ml in control group; the difference among the 5 groups was
      significant (F=15.76, P<0.0001), but the difference among the 3 single bacterin
      groups was not significant (q test, P>0.05), while the differences between other
      groups were significant (q test, P<0.01). CONCLUSIONS: The chosen bacterins in
      this study can induce the mice to produce IL-12(p70) and suppress the growth of
      S180. The effect of the combined bacterin is much better than the single
      bacterins.

PMID- 17430657
TI  - [Predictive value of in vitro MTT assay chemosensitivity test of cytotoxic drug
      activity in cervical cancer].
AB  - BACKGROUND & OBJECTIVE: In recent years, the neoadjuvant chemotherapy for
      cervical cancer has evoked more and more attention and has been used widely. But
      the chemosensitivity of individuals to various antitumor drugs is different. This
      study was to investigate the chemosensitivity of cervical cancer cells to
      antitumor drugs using in vitro MTT assay chemosensitivity test. METHODS: The
      sensitivity of fresh human cervical cancer cells from 32 patients to 9 cytotoxic
      drugs was tested using in vitro MTT assay. RESULTS: The cytotoxic activities of
      the 9 drugs for cervical cancer were in sequence from high to low as follows:
      liposomal paclitaxel, taxol, carboplatin (CBP), ifosfamide (IFO), etoposide (VP
      16), 5-fluorouracil (5-FU), cisplatin (DDP), bleomycin (BLM), and
      cyclophosphamide (CTX). Generally, cervical cancer cells were more sensitive to
      paclitaxel, taxol, and CBP than to other drugs (P<0.05) with inhibition rates of
      56.56%, 55.66%, and 46.81%, respectively. Stage Ib1 cervical cancer cells were
      more sensitive to taxol, paclitaxel, and CBP than to other drugs with inhibition
      rates of 58.71%, 53.00%, and 49.25%, respectively; stage Ib2 cervical cancer
      cells were more sensitive to paclitaxel and taxol than to other drugs with
      inhibition rates of 65.26% and 50.06%. Both moderately and poorly differentiated
      squamous cell cancer cells were more sensitive to taxol, paclitaxel, and CBP than
      to other drugs with inhibition rates of 52.01%, 49.21%, and 40.02% for the
      former, and 60.02%, 61.16%, and 48.75% for the latter. CONCLUSIONS: MTT assay, a
      sensitive and widely used chemosensitivity testing method, is helpful in
      sensitive drug screening and neoadjuvant chemotherapy regimen selection for
      cervical cancer. Cervical cancer cells are more sensitive to paclitaxel, taxol,
      and CBP than to other tested drugs in this study.

PMID- 17430658
TI  - [Transdermal fentanyl in treating severe painful mucositis caused by autologous
      hematopoietic stem cell transplantation].
AB  - BACKGROUND & OBJECTIVE: The incidence of mucositis caused by autologous
      hematopoietic stem cell transplantation (AHSCT) is relatively high. The severe
      painful mucositis can reduce the quality of life of patients obviously.
      Transdermal fentanyl is efficient in treating chronic pain of cancer, and also
      can relieve the severe pain of mucositis resulted from chemotherapy. This study
      was to investigate the efficacy and safety of transdermal fentanyl for the severe
      painful mucositis caused by AHSCT. METHODS: A total of 22 malignant tumor
      patients suffered from severe mucositis caused by high dose chemotherapy combined
      AHSCT. The analgesic degree before and after treatment was evaluated by the
      scores of Visual Analogue Scale (VAS) (range 0-10). The median VAS scores of all
      patients were above 4 (moderate to severe pain) before the administration of
      transdermal fentanyl. The quality of life before and after treatment was
      evaluated by the Standard of Quality of Life drew up in China in 1990. The
      adverse events after treatment were evaluated by Common Toxicity Criteria
      formulated by National Cancer Institute of the USA. RESULTS: The median VAS score
      has been decreased from baseline at 6 (4-9) to 3.5 (0-9) on Day 3, 2 (0-6) on Day
      5, 0.5 (0-8) on Day 7, 0 (0-6) on Day 10, and 0 (0-5) on Day 15 after treatment
      (P<0.001). The overall response rate was 100%, while the complete response rate
      was 45.5%. The quality of life of the patients was improved significantly
      (P<0.01). The adverse events after treatment of transdermal fentanyl included
      dizziness, somnolence, dysuria, mild and transient nausea, vomiting, discomfort
      of stomach, and so on. All the adverse events disappeared within several days
      after proper managements. Neither severe adverse event nor drug addiction was
      found. CONCLUSIONS: Transdermal fentanyl has good analgesic effect on painful
      severe mucositis induced by AHSCT. It is convenient and well tolerated, and could
      improve quality of life significantly.

PMID- 17430659
TI  - [Concurrent chemoradiotherapy followed by adjuvant chemotherapy for stage III-IVa
      nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Most studies on chemoradiotherapy for advanced
      nasopharyngeal carcinoma (NPC) showed that induction chemotherapy before
      radiotherapy could not improve the survival of the patients, but the effect of
      adjuvant chemotherapy after radiotherapy on advanced NPC is uncertain. A study
      showed that concurrent chemoradiotherapy could improve the prognosis of advanced
      NPC. This study was to evaluate the efficacy of concurrent chemoradiotherapy
      followed by adjuvant chemotherapy on stage III-IVa nasopharyngeal carcinoma
      (NPC). METHODS: A total of 80 patients with stage III-IVa NPC were randomized
      into test group (40 patients) and control group (40 patients). Test group
      received concurrent chemotherapy of weekly cisplatin (25 mg/m2) for 6 weeks, and
      conventional radiotherapy of standard fractionation at 2 Gy/day to a total of 70
      Gy to the nasopharynx, followed by adjuvant chemotherapy of cisplatin (25 mg/m2)
      and 5-fluorouracil (1000 mg/m2) daily for 3 days and repeated every 3 weeks for 3
      cycles. Control group received only conventional radiotherapy. RESULTS: After
      treatment, 34 patients in test group and 32 in control group achieved complete
      remission (CR) (P>0.05); the CR rate of neck lymph node was significantly higher
      in test group than in control group (92.5% vs. 75.0%, P<0.05). The 1-, 3-, 5-year
      overall survival rates were significantly higher in test group than in control
      group (92.7% vs. 81.2%, 78.6% vs. 52.7%, 64.2% vs. 42.3%, P<0.01). The 1-, 3-, 5
      year disease-free survival rates were significantly higher in test group than in
      control group (91.2% vs. 78.2%, 76.7% vs. 51.9%, 63.5% vs. 40.3%, P<0.01). The 5
      year distant metastasis rate was significantly lower in test group than in
      control group (15.0% vs. 35.0%, P<0.05). Grade III mucositis was more frequently
      observed in test group than in control group (75.0% vs. 25.0%, P<0.01).
      CONCLUSION: Concurrent chemoradiotherapy followed by adjuvant chemotherapy could
      improve the CR rate of neck lymph node, overall survival, and disease-free
      survival of stage III-IVa NPC patients, suppress distant metastasis, but increase
      the risk of grade III mucositis.

PMID- 17430660
TI  - [Weekly paclitaxel with concurrent intensity-modulated radiotherapy for
      nasopharyngeal carcinoma: outcomes of a tolerance trial].
AB  - BACKGROUND & OBJECTIVE: Concurrent chemoradiotherapy has definite effect on local
      regionally advanced nasopharyngeal carcinoma (NPC). Paclitaxel is confirmed by
      clinical trail to be one of the most effective single drugs for NPC. This study
      was to define the maximal tolerant dose (MTD) of paclitaxel in weekly paclitaxel
      with concurrent intensity-modulated radiotherapy (IMRT) for local-regionally
      advanced NPC. METHODS: Naive patients with locally advanced NPC were enrolled
      into this dose-escalating study. Adverse events were graded according to Common
      Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). Primary end
      points were determined by dose-limiting toxicity (DLT). The starting dose of
      paclitaxel was 30 mg.(m(2).w)(-1), with a subsequent dose escalation of 10
      mg.(m(2).w)(-1). IMRT was given to the nasopharynx and the upper neck; the lower
      neck was treated by a single anterior field irradiation. The prescription dose
      was 68 Gy by 30 fractions to the nasopharynx gross tumor, and 60-66 Gy by 30
      fractions to the positive neck lymph nodes. RESULTS: From Apr. 2004 to Sep. 2004,
      15 patients received complete chemoradiotherapy, and all of them were eligible
      for toxicity evaluation. On the first two dose levels of 30 mg.(m(2).w)(-1) and
      40 mg.(m(2).w)(-1), no patient experienced DLT. On the next dose level of 50
      mg.(m(2).w)(-1), 1 patient experienced DLT of grade 3 mucositis for 4 weeks, and
      among the additional 3 patients no one developed DLT. On the forth dose level of
      60 mg.(m(2).w)(-1), all the patients developed grade 3 mucositis for more than 3
      weeks, and the dose-escalating trial stopped. All of the 15 patients achieved
      clinical complete remission (CR) in the local site; 14 (93.3%) achieved CR in the
      regional site, and 1 achieved partial remission (PR) and got CR 1 month later.
      After a median follow-up of 20 months, 1 patient developed multiple bone
      metastases, and 14 kept disease-free. CONCLUSION: The MTD of paclitaxel in weekly
      paclitaxel with concurrent IMRT for local-regionally advanced NPC is 50
      mg.(m(2).w)(-1), with mucositis as DLT.

PMID- 17430661
TI  - [Peripheral blood stem cell transplantation for 53 patients with malignant
      hematologic diseases].
AB  - BACKGROUND & OBJECTIVE: Hematopoietic stem cell transplantation could improve the
      prognosis of malignant hematologic diseases. Peripheral blood stem cell
      transplantation (PBSCT) has been gradually used as an alternative to bone marrow
      transplantation (BMT). This study was to observe the efficacy of allogeneic PBSCT
      (allo-PBSCT) or autologous PBSCT (auto-PBSCT) on malignant hematologic diseases.
      METHODS: From Jul. 2003 to May 2006, 53 patients with malignant hematologic
      diseases underwent PBSCT in the First Affiliated Hospital of Zhengzhou
      University. PBSCs were mobilized with granulocyte colony-stimulating factor (G
      CSF) or chemotherapy combined with G-CSF. Auto-PBSCT group received infusion of
      CD34+ cells at a median of 3.0x10(6) cells/kg; allo-PBSCT group received infusion
      of CD34+ cells at a median of 6.2x106 cells/kg. MAC regimen was used in auto
      PBSCT group as conditioning regimen; amended BU/CY regimen was used in allo-PBSCT
      group. Methotrexate (MTX) combined with cyclosporine A (CsA) and MMF was used for
      graft-versus-host disease (GVHD) prophylaxis. Antilymphocyte globulin (ALG) was
      used in 1 patient with 1 mismatched locus in allo-PBSCT group. RESULTS: The
      median time for neutrophils to reach 0.5x10(9)/L and platelets to reach
      20x10(9)/L were 13 days and 19 days in auto-PBSCT group, 12 days and 15 days in
      allo-PBSCT group. In allo-PBSCT group, grade I-III acute GVHD occurred in 31.4%
      cases, and chronic GVHD developed in 71.4% cases. The relapse rate was 38.9% in
      auto-PBSCT group and 5.7% in allo-PBSCT group. The 700-day disease-free survival
      rate (DFS) was 57.9% in auto-PBSCT group, and 69.5% in allo-PBSCT group.
      CONCLUSIONS: PBSCT can provide rapid hematopoietic reconstitution. It is a better
      choice for the cure of malignant hematologic diseases.

PMID- 17430662
TI  - [Efficacy of docetaxel combined capecitabine on metastatic breast cancer].
AB  - BACKGROUND & OBJECTIVE: Few treatment options are available for metastatic breast
      cancer with resistance to both anthracycline-and taxane-based chemotherapy
      regimens. Docetaxel combined capecitabine (DC regimen) is approved as a new
      active regimen for metastatic breast cancer. This study was to explore the
      efficacy of DC regimen on metastatic breast cancer, and evaluate its safety.
      METHODS: A total of 31 metastatic breast cancer patients received DC regimen
      during each 3-week chemotherapy cycle. All patients received oral administration
      of capecitabine (1250 mg/m(2)) twice daily, within 30 min after meal on day 1 to
      Day 14, and infusion of docetaxel (75 mg/m(2)) on the first day of each 3-week
      cycle. All patients received prophylactic therapy with oral dexamethasone (8 mg)
      twice daily on 3 successive days. RESULTS: A total of 116 cycles of DC regimen
      were administered, with a median of 3.7 cycles. The objective response rate was
      41.9%, with a complete remission (CR) rate of 9.6%. The most frequent treatment
      related adverse events were fatigue, leukopenia, nausea, vomiting, hand-foot
      syndrome, and stomatitis. The median follow-up was 10.8 months (range 2-23
      months). Two patients were died of tumor progression. CONCLUSION: The combination
      of docetaxel and capecitabine provides a well-tolerated and active chemotherapy
      regimen for metastatic breast cancer.

PMID- 17430663
TI  - [Efficacy and toxicity of FOLFOX6 regimen in treating colorectal cancer patients
      with liver metastasis].
AB  - BACKGROUND & OBJECTIVE: FOLFOX6 regimen has been used in treating advanced
      colorectal cancer for a period, but there is no systemic study on FOLFOX6 regimen
      in treating Chinese colorectal cancer patients with liver metastasis. This study
      was to evaluate the efficacy of FOLFOX6 regimen on Chinese colorectal cancer
      patients with liver metastasis, and observe the adverse events. METHODS: Ninety
      one colorectal cancer patients with liver metastasis were treated by FOLFOX6
      regimen. FOLFOX6 regimen consisted of 2-hour infusion of oxaliplatin (100
      mg/m(2)) and 2-hour infusion of leucovorin (CF) (400 mg/m(2)) on Day l, followed
      by 5-fluorouracil (5-FU) bolus (400 mg/m(2)) on Day 1 and 46-hour infusion (2.4
      g/m(2)). FOLFOX6 regimen was repeated at 2-week intervals. The clinical efficacy
      and adverse events were evaluated. RESULTS: The objective response rate for all
      patients was 40.7%, with 4 cases of complete remission (CR), 33 partial remission
      (PR), 19 stable disease (SD), and 35 progressive disease (PD). There was no
      significant difference in objective response rate between the patients with and
      without previous treatment (P>0.05). The median survival time was 17.0 months for
      all patients, 20.0 months for the patients without previous treatment, and 12.0
      months for the patients with previous treatment. The time to progress (TTP) was
      7.0 months for all patients, 9.0 months for the patients without previous
      treatment, and 6.0 months for the patients with previous treatment. Peripheral
      neuritis, gastrointestinal reaction, and myelosuppression were major adverse
      events. All patients with 5-FU-associated adverse events recovered after
      treatment. CONCLUSION: FOLFOX6 regimen can be used in treating colorectal cancer
      with liver metastasis for its efficacy and less toxicity.

PMID- 17430665
TI  - [Bone marrow immunophenotypes of 112 cases of lymphoid system malignant
      diseases].
AB  - BACKGROUND & OBJECTIVE: Diagnosis of lymphocytic leukemia and non-Hodgkin's
      lymphoma (NHL) is based on bone marrow morphology. Immunophenotyping will make
      diagnosis more precise through analyzing the origin and differentiation status of
      tumor, which is necessary for treatment and prognosis prediction. This study was
      to analyze the immunophenotypic characteristics of lymphocytic leukemia and NHL
      with bone marrow involvement using flow cytometry (FCM). METHODS: Bone marrow
      specimens from 112 patients with lymphocytic leukemia or NHL with bone marrow
      involvement were detected by FCM using antibodies of T, B and myeloid cell
      series. Using CD45/SSC gating strategy, the samples were analyzed with 5
      parameters (FSC, SSC, McAb1-FITC, McAb2-PE, CD45-cytochrome). RESULTS: In 45
      cases of precursor B lymphoblastic leukemia/lymphoma (B-ALL/LBL), the antigens
      were mainly CD19, CD10, TdT, CD34, HLA-DR, and CD20. In 32 cases of precursor T
      lymphoblastic leukemia/lymphoma (T-ALL/LBL), the antigens were mainly CD7, CD5,
      cytoplasmic (Cy)CD3, TdT, CD34, surface CD3 (sCD3), and HLA-DR. Of the 77 cases
      of precursor ALL/LBL, 28(36.4%) expressed myeloid-associated antigens, such as
      CD13 and CD33; 9 (20.0%) cases of B-ALL/LBL coexpressed CD20 and CD34; 28(87.5%)
      cases of T-ALL/LBL coexpressed cyCD3 and TdT. Among the 35 cases of mature B-cell
      malignancies, 17 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma
      (CLL/SLL) mainly expressed CD19, CD20, CD5, HLA-DR, with coexpression of CD19 and
      CD5; 4 cases of diffuse large B-cell lymphoma (DLBCL) mainly expressed CD19,
      CD20, CD10, and HLA-DR; 3 cases of Burkitt's lymphoma (BL) mainly expressed CD19,
      CD10, CD20, and sIgM; 1 case of mantle cell lymphoma (MCL) expressed CD5, CD19,
      CD20, and HLA-DR. Among the 10 mature T-cell malignancies, 5 cases of
      unspecialied peripheral T-cell lymphoma (PTCL) mainly expressed sCD3, CD5 and
      CD7, CD4 or CD8; 1 case of anaplastic large cell lymphoma (ALCL) expressed sCD3
      and HLA-DR; 4 cases of NK/T-cell malignancies expressed CD56 and HLA-DR, CD4 or
      CD8 or CD7. Mature lymphoid system malignancies didn't express early antigens,
      such as CD34 and TdT, but expressed myeloid-associated antigens, especially CD13
      and CD33. CONCLUSION: Multiparameter FCM can not only provide data of cell
      lineage and differentiation status but also detect phenotypic aberrancies, which
      is helpful for minimal residual disease detecting.

PMID- 17430664
TI  - [Efficacy of gefitinib on advanced non-small cell lung cancer of bilateral
      diffuse or unilateral giant mass type].
AB  - BACKGROUND & OBJECTIVE: No more survival improvement could be obtained in
      advanced non-small cell lung cancer (NSCLC) today with chemotherapy or
      radiotherapy. Clinical trails showed the antitumor effect of gefitinib on NSCLC
      with individual differences. This study was to select NSCLC patients of suitable
      type by comparing the efficacy of gefitinib on advanced NSCLC of bilateral
      diffuse type and unilateral giant mass type. METHODS: Fifty advanced NSCLC
      patients of bilateral diffuse type (20 cases) and unilateral mass type (30 cases)
      received treatment of gefitinib. The efficacy of gefitinib on advanced NSCLC
      between the 2 groups was compared. RESULTS: The median time to symptom
      improvement was significantly shorter in bilateral diffuse group than in
      unilateral mass group (4 days vs. 7 days, P<0.01). The disease control rate was
      significantly higher in bilateral diffuse group than in unilateral mass group
      (75% vs. 20%, P<0.01). The median progression-free time was significantly longer
      in bilateral diffuse group than in unilateral mass group (9.5 months vs. 3.6
      months, P<0.01). Drug-related adverse events were similar in the 2 groups.
      CONCLUSIONS: Gefitinib is more effective to bilateral diffuse type NSCLC than to
      unilateral giant mass type NSCLC. It can be considered as the second-line
      medicine for bilateral diffuse type NSCLC.

PMID- 17430666
TI  - [Retrospective analysis of 98 cases of breast cancer with liver metastasis].
AB  - BACKGROUND & OBJECTIVE: The prognosis of breast cancer patients with liver
      metastasis is poor. How to improve treatment efficacy and prolong survival of
      these patients is a challenge in clinic. This study was to explore the efficacy
      of chemotherapy and transcatheter arterial chemoembolization (TACE) on breast
      cancer patients with liver metastasis, and analyze prognostic factors. METHODS:
      Clinical data of 98 breast cancer patients with liver metastasis, treated from
      1996 to 2005 in Cancer Center of Sun Yat-sen University, were analyzed
      retrospectively. The prognostic factors correlated to clinical features and
      treatment approaches were determined using Cox multivariate model. RESULTS: The
      total response rate was 45.9% for all patients, 48.6% for the 74 patients
      received systemic chemotherapy, 23.1% for the 13 patients received TACE, and
      54.6% for the 11 patients received chemotherapy plus TACE. At a median follow-up
      of 17 months (3-56 months), the 1-, 2-, 3-, and 4-year survival rates were 36%,
      19%, 13%, and 3%, respectively; the median survival was 17 months (3-56 months),
      and the progression-free survival was 6 months (0-50 months). CONCLUSION: The
      combination of systemic chemotherapy and TACE may prolong the survival of breast
      cancer patients with liver metastasis.

PMID- 17430667
TI  - [Clinical comparison of GC regimen (gemcitabine and cisplatin) versus FEC regimen
      (fluorouracil, epirubicin, and cyclophosphamide) as neoadjuvant chemotherapy for
      breast cancer].
AB  - BACKGROUND & OBJECTIVE: Neoadjuvant chemotherapy plays a crucial role in treating
      breast cancer, but there is no standard regimen. Recently, FEC regimen [5
      fluorouracil (5-FU), epirubicin (EPI), plus cyclophosphamide (CTX)] is the most
      commonly used; gemcitabine (GEM) is also a new active antimetabolite for breast
      cancer, however, the experience with neoadjuvant gemcitabine is limited. This
      study was to compare the efficacy of GC regimen and FEC regimen on breast cancer,
      and observe the adverse events. METHODS: From Mar. 2003 to Sep. 2005, 62 patients
      with stage II-III breast cancer were treated with 2 cycles of either GC regimen
      or FEC regimen before operation. The 22 patients in GC group received GEM (1000
      mg/m(2)) by intravenous injection on Day 1 and Day 8, and DDP (75 mg/m(2)) by
      intravenous injection on Day 2. The 40 patients in FEC group received EPI (50
      mg/m(2)) by intravenous injection on Day 1, CTX (500 mg/m(2)) by intravenous
      injection on Day 1 and Day 8, and 5-FU (500 mg/m(2)) by 4-hour continuous
      infusion on Day 1 and Day 8. Clinical response and adverse events were assessed
      after neoadjuvant chemotherapy. RESULTS: The overall response rate (RR) was 63.6%
      in GC group and 72.5% in FEC group. After GC therapy, 4 patients showed clinical
      complete remission (cCR), 2 pathologic complete remission (pCR), 10 partial
      remission (PR), 8 stable disease (SD)u while after FEC therapy, 9 patients showed
      cCR, 5 pCR, 20 PR, 10 SD. The most common adverse events were anemia, leukopenia,
      and nausea/vomiting. More cases of leukopenia were observed in GC group (18/22,
      P<0.05), and more cases of anemia in FEC group (29/40, P<0.05); the occurrence
      rates of gastroenteric reaction were similar in both groups. Only 1 patient in GC
      group suffered from oral mucositis; no renal toxicity and neurotoxicity were
      observed. CONCLUSIONS: GC and FEC regimens are both effective for breast cancer
      with tolerable adverse events. The efficacy of FEC regimen is better than that of
      GT regimen.

PMID- 17430668
TI  - [Comparison of therapeutic efficacy between TP regimen and CBP regimen on
      epithelial ovarian cancer after optimal cytoreductive operation].
AB  - BACKGROUND & OBJECTIVE: The most effective treatment for epithelial ovarian
      cancer is the combination of surgical operation and chemotherapy. Complete
      removal of the tumor is the key of surgical treatment; TP regimen (paclitaxel
      plus carboplatin) is the preference for postoperative chemotherapy, but its
      superiority is controversial. This study was to compare the efficacy of TP
      regimen and CBP regimen (cyclophosphamide, bleomycin plus carboplatin/cisplatin)
      on epithelial ovarian cancer. METHODS: Clinical data of 125 patients with stage
      IIb-IV epithelial ovarian cancer, underwent optimal cytoreductive operation and
      received regular postoperative chemotherapy in Cancer Center of Sun Yat-sen
      University, were analyzed. Of the 125 patients, 65 were treated with CBP regimen,
      60 were treated with TP regimen. The 3-year survival statuses and main adverse
      events were compared between the 2 groups. RESULTS: The 3-year survival rates
      were 69.2% in CBP group and 75.3% in TP group (P=0.473); the 3-year tumor-free
      survival rates were 38.5% and 43.3%, respectively (P=0.580); the medians of
      progression-free survival time of the patients with recurrent disease were 12
      months and 13 months, respectively (P=0.672). The comparisons of overall survival
      curves and tumor-free survival curves between the 2 groups showed no significant
      differences, too (P=0.285 and P=0.517). The comparisons of adverse effects
      between the 2 groups showed no significant differences except for neurologic
      toxicity. CONCLUSION: TP regimen and CBP regimen have identical therapeutic
      effects when used as first-line chemotherapy regimen for epithelial ovarian
      cancer after optimal cytoreductive operation.

PMID- 17430669
TI  - [Expression and clinical significance of Mcl-1 in T-cell non-Hodgkin's lymphoma].
AB  - BACKGROUND & OBJECTIVE: The prognosis of T-cell non-Hodgkin's lymphoma (T-NHL) is
      poor. Overexpression of myeloid cell leukemia-1 (Mcl-1) gene could inhibit
      irradiation-and drug-induced apoptosis in several lymphoma cell lines. This study
      was to detect the expression of Mcl-1 in T-NHL of various subtypes, and explore
      its correlation to clinicopathologic features and prognosis of T-NHL. METHODS:
      The expression of Mcl-1 protein in 72 specimens of T-NHL was detected by
      immunohistochemistry. The clinical features, treatments, and outcomes of the T
      NHL patients were analyzed retrospectively. RESULTS: The weak positive rates of
      Mcl-1 were 44.4% in precursor T lymphoblastic lymphoma (T-LBL), 0% in anaplastic
      large T-cell lymphoma (ALCL), and 18.9% in other peripheral T-cell lymphoma
      (PTL); the positive rates were 0%, 100%, and 49.1%, respectively (P<0.001). Weak
      diffuse cytoplasmic staining of Mcl-1 was detected in T-LBL, and strong
      cytoplasmic staining with perinuclear accentuation was detected in ALCL. The
      overall survival time was significantly longer in the PTL patients with high Mcl
      1 expression than in the PTL patients with weak/negative Mcl-1 expression (>32
      months vs. 15 months, P=0.007), and longer in the T-LBL patients without Mcl-1
      expression than in the T-LBL patients with weak Mcl-1 expression (21 months vs. 7
      months, P=0.58). CONCLUSIONS: The intensities of Mcl-1 expression in T-NHL of
      various histological subtypes are different. It is specifically highly expressed
      in ALCL. High expression of Mcl-1 is correlated to better prognosis of PTL.

PMID- 17430670
TI  - [Advancement in endocrine therapy for breast cancer].
AB  - Endocrine therapy with certain effect is an important part of combined therapy
      for hormone receptor-positive breast cancer. The endocrine therapy for breast
      cancer has made progress with the development of new endocrine drugs. Now,
      tamoxifen is still the standard endocrine therapeutic drug for the premenopausal
      patients, but aromatase inhibitors can bring more benefit for the postmenopausal
      patients. Several large-scale clinical trials about aromatase inhibitors and
      medical ovarian ablation are ongoing and attract attention widely. This review
      overviewed the endocrine therapy for breast cancer, and mainly introduced its
      recent advancement.

PMID- 17430671
TI  - [A case report of paclitaxel combined with carboplatin for poorly differentiated
      prostate cancer with renal failure].

PMID- 17430672
TI  - [A case report of composite lymphoma].

PMID- 17430673
TI  - Saving lives in acute ST-elevation myocardial infarction: the door-to-balloon
      initiative.

PMID- 17430674
TI  - Are vasodilators still indicated in the treatment of severe aortic regurgitation?
AB  - Aortic regurgitation (AR) is a valve disease that causes severe complications and
      reduces life expectancy. Surgical correction is required in the late stages of
      the disease. In less advanced forms, treatment with vasodilators is a
      consideration. The available evidence suggests that this type of treatment has a
      favorable effect on the consequences of AR, particularly left ventricular
      remodeling. However, the impact of vasodilators on clinical endpoints
      complicating the course of AR remains in doubt. The limited evidence supporting
      or opposing the utilization of vasodilators in AR hinders drawing firm
      conclusions and emphasizes the process of individualized interpretation of the
      clinical presentation of patients with the disease.

PMID- 17430675
TI  - What is the proper place of the Ross procedure in our modern armamentarium?
AB  - Despite nearly four decades of experience, the role of pulmonary valve
      autotransplantation (Ross procedure) in the treatment of aortic valve disease in
      adults and children continues to evolve and remains controversial. As the picture
      of late results has unfolded, alternating waves of enthusiasm and caution have
      characterized its use and have led to ongoing refinements in indications and
      operative technique. At present, it is seen as indispensable in the treatment of
      aortic valve disease in infants and small children (for whom no satisfactory
      replacement alternative exists and for whom growth is essential), attractive for
      adolescents and young adults who wish to avoid anticoagulants because of
      childbirth and lifestyle considerations, a reasonable option for selected adults
      who desire biologic solutions with potentially better durability than
      conventional bioprostheses, and contraindicated for the elderly and those with
      connective tissue disorders. Young patients with bicuspid aortic valve are the
      most common potential recipients, but also the most controversial, because of the
      risk of autograft dilatation. Optimal matching of prosthesis to patient is a
      clinical challenge for all caretakers involved in the treatment of valvular heart
      disease; this review provides guidelines to identify those patients who will
      benefit most from the Ross procedure, and those for whom it is inadvisable.

PMID- 17430676
TI  - Reassessment of statins to retard the progression of aortic stenosis.
AB  - Aortic valve stenosis is the most common indication for surgical valve
      replacement in the United States and Europe. For years, this valve lesion was
      thought to be a passive degenerative disease. In the past decade there have been
      a number of studies indicating that the risk factors for valvular heart disease
      are the same as those for vascular atherosclerosis. This correlation with
      atherosclerosis and valvular heart disease indicates that medical therapy may
      have a role in slowing the progression of this disease process. Currently, the
      retrospective studies indicate that medical therapy slows the progression of this
      disease. The prospective data are currently conflicting in terms of the final
      outcomes for treating the disease process with medical therapy. This review
      outlines the growing number of clinical studies implicating the potential for
      medical therapy in this patient population.

PMID- 17430677
TI  - A practical approach to the quantification of valvular regurgitation.
AB  - This article reviews the methods of determining the severity of mitral and aortic
      regurgitation, primarily the quantitation using Doppler echocardiography. The
      Doppler methods, including spatial mapping, proximal flow convergence, vena
      contracta, continuous-wave Doppler density, and upstream or downstream effects
      are explained. Various practical pitfalls and performance issues that impact the
      reliability of these techniques are discussed.

PMID- 17430678
TI  - The management of functional mitral regurgitation.
AB  - Mitral regurgitation (MR) may be classified into two major categories: primary
      and secondary (functional). In primary MR, disease of the valve itself (eg,
      myxomatous degeneration, rheumatic disease) causes valve incompetence, producing
      left ventricular (LV) volume overload. To compensate, the left ventricle must
      enlarge in order to increase its volume-pumping capacity. If volume overload is
      prolonged and severe, the adverse effects of remodeling together with activation
      of deleterious neurohumoral systems leads to myocardial damage. It is quite clear
      that correction of the volume overload causes myocardial healing and reverse
      remodeling. Conversely, in secondary MR, the valve itself is normal. Ventricular
      dilatation and wall motion abnormalities cause papillary muscle displacement and
      annular dilatation, causing a normal mitral valve to leak. In this situation it
      is not clear whether or when correction of the MR is beneficial because the MR
      was not the primary cause of the LV dysfunction to begin with. Other areas of
      uncertainty include the type of correction to be used and whether burgeoning
      technologies for percutaneous valve repair will be useful.

PMID- 17430679
TI  - Methodology for quantifying absolute myocardial perfusion with PET and SPECT.
AB  - Noninvasive quantitative measurement of myocardial perfusion has played an
      important role in cardiac research and also has potential applications in
      clinical imaging. Positron emission tomography (PET) methods for measuring
      absolute perfusion are well established, although the need for an on-site
      cyclotron has restricted its use to a limited number of centers. Single-photon
      emission CT (SPECT) also has potential for quantifying myocardial perfusion and
      has more widespread availability. In this article we review the basic principles
      of absolute myocardial perfusion quantification and the radiopharmaceuticals that
      are available for both PET and SPECT. We also examine the extent to which recent
      developments in instrumentation have increased the practicality of absolute
      perfusion quantification in PET and the potential for absolute quantification in
      SPECT.

PMID- 17430680
TI  - Hybrid SPECT-CT: integration of CT coronary artery calcium scoring and
      angiography with myocardial perfusion.
AB  - A natural extension of current imaging paradigms for diagnosing coronary artery
      disease may well be the integration of CT with myocardial perfusion single-photon
      CT (SPECT). Although there is a wealth of clinical information regarding the
      utility of SPECT, the value of CT in the cardiology arena has only recently been
      explored. CT has the advantage of detecting coronary atherosclerosis at its
      earliest stages, allowing initiation of appropriate therapeutic measures well
      before development of obstructive coronary artery disease. However, SPECT can
      clarify the anatomic findings of CT based on a functional assessment of
      myocardial blood flow, thereby guiding management decisions. Hybrid imaging with
      SPECT and CT angiography may prove important from a diagnostic and therapeutic
      view point in several clinical scenarios, and it is likely that over the next
      decade fusion imaging may more precisely tailor therapy, reduce healthcare costs,
      and improve patient outcome.

PMID- 17430681
TI  - Imaging of matrix metalloproteinase activation and left ventricular remodeling.
AB  - Although left ventricular (LV) remodeling may be adaptive in early phases of
      cardiac injury, continued remodeling is a pathologic process that is associated
      with poor prognosis and diminished cardiac function. Matrix metalloproteinases
      (MMPs) are a family of proteolytic enzymes involved in the degradation of
      myocardial extracellular proteins and have been implicated in adverse cardiac
      remodeling. There is a growing body of literature that supports the role of
      specific MMPs in cardiac remodeling in both animal models and clinical studies.
      Conventional imaging of physiologic indices, such as perfusion and function, have
      been used to monitor LV remodeling. Recently, the potential advantage of targeted
      imaging of MMPs has been demonstrated, particularly if this is linked with
      physiologic imaging.

PMID- 17430682
TI  - Myocardial metabolism and cardiac performance in obesity and insulin resistance.
AB  - Obesity, insulin resistance, and their frequent complication of type 2 diabetes
      are risk factors for left ventricular diastolic dysfunction, systolic
      dysfunction, and clinical heart failure. Although obesity, insulin resistance,
      and diabetes are risk factors for coronary artery disease, and hence ischemic
      cardiomyopathy-related heart failure, there is increasing evidence that these
      three risk factors are implicated in the development of cardiac dysfunction not
      related to epicardial coronary disease. There are several mechanisms by which
      this triad may cause cardiac dysfunction, including alterations in myocardial
      metabolism, which may initially be adaptations but evolve into maladaptive
      responses over time. Recent advances in our understanding of these mechanisms
      will aid in the development of novel therapies, including metabolic manipulations
      that could prevent and treat cardiac dysfunction in patients with obesity,
      insulin resistance, and diabetes.

PMID- 17430683
TI  - The role and regulation of cardiac angiotensin-converting enzyme for noninvasive
      molecular imaging in heart failure.
AB  - Congestive heart failure is a pathologic condition characterized by progressive
      decrease in left ventricular contractility and consequent decline of cardiac
      output. There is convincing clinical and experimental evidence that the renin
      angiotensin system (RAS) and its primary effector peptide, angiotensin II, are
      linked to the pathophysiology of interstitial fibrosis, cardiac remodeling, and
      heart failure. In addition to the traditional endocrine or circulating RAS, an
      active tissue RAS has been characterized. Tissue angiotensin-converting enzyme
      and locally synthesized angiotensin II, for example, by chymase, exert local
      trophic effects that modulate gene expression, which regulates growth and
      proliferation in both myocytes and nonmyocytes. The existence of the tissue RAS
      offers an opportunity for targeted imaging, which may be of considerable value
      for guiding medical therapy.

PMID- 17430685
TI  - Use of progression-free survival as a valid endpoint in phase II cancer clinical
      trials.

PMID- 17430684
TI  - Delayed recovery of fatty acid metabolism after transient myocardial ischemia: a
      potential imaging target for "ischemic memory".
AB  - The myocardium preferentially oxidizes free fatty acids for energy production.
      However, the dependency of this metabolic pathway on oxygen makes this process
      vulnerable to ischemia. The energy requirements of the myocardium are
      subsequently met by the oxidation of carbohydrates, particularly glucose.
      Recovery of fatty acid metabolism lags behind restoration of perfusion, resulting
      in the phenomenon of metabolic stunning. This decrease of fatty acid utilization
      following ischemia can be imaged with fatty acid radiotracers, particularly beta
      Methyl-p-(123)I-iodophenyl pentadecanoic acid (BMIPP), which demonstrates
      markedly limited metabolism via beta-oxidation, resulting in prolonged retention
      in the cardiomyocyte. Thus, in patients presenting with chest pain and no prior
      myocardial infarction, abnormal BMIPP uptake at rest reflects metabolic
      alteration caused by the preceding ischemia, also termed ischemic memory.

PMID- 17430686
TI  - Recent advances in therapy for gastrointestinal stromal tumors.
AB  - Sarcomas comprise less than 1% of all cancers. Gastrointestinal stromal tumor
      (GIST) is the most common form of sarcoma and can vary in size and clinical
      outcome from an incidental finding at operation to life-threatening metastatic
      disease. Surgery is the standard of care for primary disease, and the oral drug
      imatinib is the standard of care for metastatic disease. Sunitinib was approved
      in the United States in early 2006 for GIST that is refractory to imatinib. The
      pathology of GIST, surgical options for primary and metastatic disease, and
      findings leading to the use of imatinib and sunitinib for GIST are highlighted in
      this review.

PMID- 17430687
TI  - Pancreatic cancer: an update.
AB  - Pancreatic cancer is refractory to most chemotherapy. For many years, the only
      active agent for this disease was gemcitabine, which has very modest activity.
      Two new regimens, gemcitabine plus erlotinib and gemcitabine plus capecitabine,
      have recently demonstrated statistically significant survival improvements
      compared with single-agent gemcitabine. Several key negative studies have also
      been reported recently. This review discusses recent trials that have changed the
      standard of care for patients with advanced pancreatic cancer.

PMID- 17430688
TI  - New developments in the treatment of gastrointestinal neuroendocrine tumors.
AB  - Patients with metastatic gastrointestinal neuroendocrine tumors have
      traditionally been faced with few effective treatment options. Somatostatin
      analogs often successfully control symptoms of hormonal hypersecretion but seldom
      result in tumor regression. Some patients with hepatic metastases are also
      candidates for ablative therapies such as surgical debulking or embolization. The
      role of systemic agents such as interferon alfa or cytotoxic chemotherapy remains
      ill defined. The more prevalent use of these modalities has been restricted by
      low tumor response rates and the potential for toxicity. Novel agents, including
      radiolabeled somatostatin analogs, inhibitors of the vascular endothelial growth
      factor pathway, and inhibitors of mammalian target of rapamycin, have shown
      promising activity in recent clinical studies. Continued investigation of these
      agents should render a better understanding of their efficacy in patients with
      advanced neuroendocrine tumors.

PMID- 17430689
TI  - Combined-modality therapy for esophageal and gastroesophageal junction cancers.
AB  - The optimal management of locoregional esophageal cancer is controversial.
      Preoperative concomitant chemoradiotherapy (two courses of cisplatin and 5
      fluorouracil plus 50 Gy of radiation) may provide benefit in survival and local
      control compared with surgery alone and is a reasonable alternative to surgery
      alone in stages IIB, III, and possibly stage IVa disease. This benefit is less
      clear in stages I and IIA, for which surgery alone is thus a reasonable option.
      Preoperative chemotherapy without radiation also provides a survival benefit
      compared with surgery alone, but data are insufficient to conclude it is superior
      to preoperative chemoradiotherapy. Control of distant disease remains a problem
      with preoperative chemotherapy and preoperative chemoradiotherapy.

PMID- 17430692
TI  - Clinical trials in metastatic hormone-refractory prostate cancer: improving
      docetaxel therapy by targeting bone-related growth factors.

PMID- 17430691
TI  - Rationale for, and approach to, studying modifiers of risk in persons with a
      genetic predisposition to colorectal cancer.
AB  - We address the issue of modifiers of risk for persons who are, on average, at
      high risk of colorectal cancer due to carrying germline genetic mutations. We
      discuss how to estimate risk and assess modifiers using data from mutation
      carrying families. A critical analytical issue is the adjustment for how families
      have been sampled (ascertainment). Only a few published studies have made
      appropriate adjustments and have mostly reported lifetime risks of less than 50%.
      Incomplete penetrance and differences in risk by subcategories are consistent
      with the existence of genetic and/or environmental risk -modifiers. Data from
      large cohorts of carriers are required to study such modifiers with precision.

PMID- 17430690
TI  - Shifting from clinical to biologic indicators of prognosis after resection of
      hepatic colorectal metastases.
AB  - Following resection of hepatic colorectal metastases, there are few criteria for
      predicting which patients have more aggressive disease and are, therefore, more
      likely to experience recurrence and reduced survival. Traditionally, primary
      tumor stage, preoperative carcinoembryonic antigen level, time from primary tumor
      treatment to diagnosis of hepatic metastases (disease-free interval), hepatic
      tumor size, number of hepatic metastases, and presence of extrahepatic disease
      have been reported to be predictors of survival after resection. However, the
      data regarding the prognostic importance of these clinicopathologic factors are
      inconsistent and conflicting. Therefore, conventional clinicopathologic factors
      may be inadequate for the purposes of prognostication. More recently, there has
      been increased interest in identifying biologic indicators that may help better
      define patients at risk for recurrence after hepatic resection for colorectal
      metastases. Recent studies have shown that proliferation markers such as p53
      expression, tritiated thymidine uptake, thymidylate synthase, Ki-67, and human
      telomerase reverse transcriptase may be better predictors of outcome after
      resection of hepatic colorectal metastases. Moreover, tumor response to
      preoperative chemotherapy may also prove to be a useful predictor of outcome
      following liver resection for colorectal metastases.

PMID- 17430693
TI  - The role of lymphadenectomy in patients undergoing radical cystectomy for bladder
      cancer.
AB  - The role of regional lymph node dissection (LND) in surgical management of high
      grade, invasive transitional cell carcinoma of the bladder has evolved over the
      past several decades. The current concepts and rationale for LND in patients
      undergoing radical cystectomy for bladder cancer are reviewed and discussed.
      Evidence suggests that a more extended LND (with cephalad extent to include at
      least the common iliac vessels) for lymph node-positive and -negative patients
      undergoing radical cystectomy for bladder cancer may provide therapeutic benefits
      in addition to prognostic information. Lymph node density also provides risk
      stratification for lymph node-positive patients and may reduce the surgical bias
      and extent of the LND, both of which are currently not standardized. Although the
      absolute limits of the LND remain to be determined, an evolving body of data
      supports a more extended LND at the time of cystectomy in appropriate surgical
      candidates.

PMID- 17430694
TI  - The role of high-intensity focused ultrasound in prostate cancer.
AB  - High-intensity focused ultrasound (HIFU) has emerged in the past decade as a new
      addition to the armamentarium of treatment options for prostate cancer. Clinical
      studies have investigated its use as a treatment for clinically localized disease
      and as salvage therapy in the setting of failure after external beam
      radiotherapy. Additional studies with long-term follow-up are needed to further
      evaluate the cancer control and quality of life outcomes of this new therapeutic
      modality.

PMID- 17430695
TI  - Immunotherapy for prostate cancer.
AB  - Whereas androgen deprivation and chemotherapy have become the cornerstone of
      therapy for advanced prostate cancer, novel therapies are being developed that
      may expand upon currently available treatments. The identification of antigens
      expressed by prostate tissue and/or prostate cancer that are recognized by T
      cells or antibodies creates opportunities to develop novel immunotherapeutic
      approaches including tumor vaccines. Proteins expressed in prostate cancer
      including prostate-specific antigen, prostatic acid phosphatase, and prostate
      membrane antigen-have been used as immunologic targets for immunotherapy.
      Moreover, innovations in cancer genomics and proteomics also will aid in the
      identification of immunologic targets. Emerging trials have demonstrated that
      immunotherapy may generate not only immune responses in patients but also
      clinical responses. Future studies will be directed at capitalizing on these
      findings.

PMID- 17430696
TI  - Antibiotic pharmacodynamics and bacterial resistance: usefulness of in vitro
      models.

PMID- 17430697
TI  - Watchful waiting versus immediate antibiotic treatment in the management of acute
      otitis media in children.

PMID- 17430698
TI  - Wait-and-see versus immediate antibiotic treatment in the management of acute
      otitis media in children.

PMID- 17430699
TI  - Bacterial biofilm in upper respiratory tract infections.
AB  - The upper respiratory tract is of easy access to pathogens, and although it has
      evolved a number of defensive barriers to avoid invasion, acute and chronic
      infections of the ears, nose, and throat are common and present a huge challenge
      to the healthcare system. Though most infections are viral, mild, and self
      limiting, bacterial infection is responsible for considerable morbidity and has
      potential for life-threatening sequelae. Biofilms form when free-floating
      planktonic organisms adhere to a surface. Within a polymicrobial, biofilm
      organisms interact, exchanging metabolites, enzymes, and genetic material. The
      colony is protected, allowing bacteria to thrive in otherwise unfavorable
      conditions. A role for the biofilm in upper respiratory tract infections has been
      proposed because infections often run a persistent, remitting course, samples are
      sometimes difficult to culture, and resistance to medical management is common.
      This review presents recently published evidence of bacterial biofilms in
      established upper respiratory tract infections.

PMID- 17430700
TI  - Anti-inflammatory treatment of chronic rhinosinusitis: a shifting paradigm.
AB  - Treatment of chronic rhinosinusitis still represents an unmet medical need.
      Presently, the US Food and Drug Administration has not approved any drugs for the
      treatment of this common condition. Various inflammatory processes are involved
      in the pathogenesis of chronic rhinosinusitis. Treatment of infection and
      surgical intervention for correction of anatomical abnormalities often are
      inadequate in management when singly employed. Anti-inflammatory therapy such as
      topical cortico-steroids and more recently long-term, low-dose macrolide therapy
      have been integrated into the treatment algorithm for chronic rhinosinusitis.
      Better classification and point-of-care identification of inflammatory features
      may improve choice of anti-inflammatory therapy and thus outcome.

PMID- 17430701
TI  - Nasal colonization with methicillin-resistant Staphylococcus aureus: clinical
      implications and treatment.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has become an increasingly
      important pathogen during the past 30 years, and infections due to MRSA are
      associated with substantial morbidity and mortality. Despite intensive infection
      control measures, the prevalence of MRSA has increased significantly, and the
      organism has become endemic in many hospitals worldwide. Asymptomatic nasal
      carriage of MRSA has been identified as a major risk factor for subsequent S.
      aureus infection in multiple settings and populations. As a result, considerable
      interest exists in developing decolonization strategies, with the ultimate goal
      of reducing the incidence of MRSA infection. Approaches to decolonization have
      included the use of systemic and inhalation anti-biotics, antiseptic washes, and
      topical antimicrobials.

PMID- 17430702
TI  - The role of anaerobic bacteria in upper respiratory tract and other head and neck
      infections.
AB  - Anaerobes are common pathogens in chronic upper respiratory tract and head and
      neck infections. They can be recovered in chronic otitis media and sinusitis,
      play a role in tonsillitis, and predominate in complications of these infections,
      causing deep oral and neck infections and abscesses. In addition to their direct
      pathogenicity, they play an indirect role through the production of the enzyme
      beta-lactamase, "shielding" non-beta-lactamase-producing bacteria from
      penicillins. Failure to provide adequate therapy against anaerobes may lead to
      clinical failures. Management of anaerobic infection is complicated by the slow
      growth of these organisms, by their polymicrobial nature, and by their growing
      resistance to antimicrobials. Antimicrobials are often the only form of therapy
      needed, but surgical approach is needed in some cases. Because anaerobes often
      are mixed with aerobic organisms, the antimicrobials given should provide
      adequate coverage against all pathogens.

PMID- 17430703
TI  - Do all patients with community-acquired pneumonia need antibiotics within 4 hours
      of presentation?

PMID- 17430704
TI  - Methicillin-resistant Staphylococcus aureus as a cause of community-acquired
      pneumonia.
AB  - New pathogens have emerged that now complicate the management of community
      acquired pneumonia (CAP). Community-acquired methicillin-resistant Staphylococcus
      aureus (CA-MRSA) has emerged as a potential cause of CAP, particularly
      complicated CAP. In this literature review, the incidence, invasiveness, and
      antimicrobial management of CA-MRSA is discussed. Based on existing data and the
      rising incidence of CA-MRSA, we recommend a change in antibiotic selection for
      complicated CAP.

PMID- 17430705
TI  - Pulmonary infections in the HIV-infected patient in the era of highly active
      antiretroviral therapy: an update.
AB  - The highly active antiretroviral therapy (HAART) era began in 1996 when the
      combination of multiple antiretroviral agents was found to improve outcomes in
      HIV-infected patients. HAART has made a tremendous impact on the progression of
      HIV and on the morbidity and mortality associated with its opportunistic
      infections. HIV-positive patients who respond to HAART have a decreased incidence
      of opportunistic infections. Studies have documented close to a 50% decline in
      the incidence of pneumocystis pneumonia and bacterial pneumonia with the use of
      antiretroviral therapy. Primary and secondary prophylaxis for pneumocystis
      pneumonia can be discontinued in patients who show a sustained response to
      antiretroviral therapy. Unique to the HAART era, immune reconstitution syndrome
      is characterized by a paradoxical deterioration of a preexisting infection that
      is temporally related to the recovery of the immune system. Recently, more and
      more patients are being admitted for non-AIDS related illnesses in the HAART era.

PMID- 17430706
TI  - Procalcitonin and pneumonia: is it a useful marker?
AB  - An ideal biomarker for pneumonia should allow an early diagnosis and differential
      diagnosis from noninfectious conditions and should inform about the course and
      prognosis of the disease. Procalcitonin (PCT) covers these features better as
      compared to more commonly used biomarkers like C-reactive protein or leukocyte
      count. PCT complements and improves the assessment of pneumonia based on careful
      patient history, dedicated physical examination, and appropriate cultures.
      Importantly, a PCT-based therapeutic strategy can safely and markedly reduce
      antibiotic courses in community-acquired pneumonia. However, as is the cast with
      all diagnostic surrogate markers, PCT can be increased in noninfectious
      conditions and may remain low in bacterial infections, especially localized
      infections. This stresses the importance of follow-up measurements, because PCT
      levels in these patients often show a gradual increase during follow-up. Although
      PCT is -better than more common biomarkers for the prognosis of pneumonia and to
      predict survival and outcome, novel biomarkers show an even better prognostic
      accuracy.

PMID- 17430707
TI  - New antiretroviral agents.
AB  - Despite advances in HIV treatment and the availability of 22 approved
      antiretroviral drugs, newer compounds are needed that are better tolerated, less
      toxic, more convenient, or have improved activity against drug-resistant viruses.
      In addition to newer agents in development in traditional antiretroviral classes
      (reverse transcriptase inhibitors, protease inhibitors), a number of compounds in
      newer mechanistic classes also are under development, including entry inhibitors,
      integrase inhibitors, and maturation inhibitors. This review focuses on some of
      the investigational antiretroviral compounds that have reached clinical
      development and that offer the most promise for treatment of HIV-infected
      individuals.

PMID- 17430708
TI  - Tuberculosis, drug resistance, and HIV/AIDS: a triple threat.
AB  - The worldwide epidemics of tuberculosis (TB) and HIV/AIDS have been joined by an
      insidiously developing third epidemic of TB drug resistance. Fueled by the
      disruption of TB control programs and the explosive growth of HIV/AIDS, the
      presence of TB drug resistance, particularly multiple drug resistance, is
      worldwide and threatens the gains made in the past decades in the treatment of
      both TB and HIV. Although treatment success is possible, the diagnosis and
      treatment of drug-resistant TB is difficult. Advances in TB diagnosis and
      treatment have been minimal in the past 40 years, and there is an urgent need for
      wider distribution of available diagnostic technology and for the development and
      testing of newer rapid molecular diagnostic techniques and therapeutic agents.
      This review discusses current information about the distribution of multiple drug
      resistant and newer extensively drug-resistant TB as well as available diagnostic
      and therapeutic strategies with an emphasis on the relationship between TB drug
      resistance and HIV/AIDS.

PMID- 17430709
TI  - [The critically-ill child. How should we provide information in the ICU].

PMID- 17430710
TI  - [Prognostic indexes of mortality in pediatric intensive care units].
AB  - OBJECTIVE: To assess the validity of the Pediatric Risk of Mortality score
      (PRISM), the Pediatric Index of Mortality (PIM) and the PIM 2 in two Spanish
      pediatric intensive care units. PATIENTS AND METHODS: We prospectively studied
      241 critically ill children consecutively admitted over a 6-month period. The
      overall performance of the scoring systems was assessed by the Standardized
      Mortality Ratio (SMR), comparing observed deaths with expected deaths by each
      index. Discrimination (the ability of the model to distinguish between patients
      who live and those who die) was quantified by calculating the area under the
      receiver operating characteristic (ROC) curve. Calibration (the accuracy of
      mortality risk predictions) was calculated with the Hosmer-Lemeshow goodness-of
      fit test, in which statistical calibration is evidenced by p > 0.05. RESULTS: The
      mortality rate was 4.1 %. PRISM overestimated mortality (SMR = 0.44).
      Discrimination was better for PRISM and PIM 2 than for PIM (areas under ROC
      curves: 0.883, 0.871, and 0.800 respectively), with no significant differences.
      Finally, calibration was acceptable for PIM 2 (x2 (8) = 4.8730, p 0.8461) and for
      PIM (x2 (8) = 8.0876, p 0.5174), but no statistical calibration was found for
      PRISM (x2 (8) = 15.0281, p 0.0133). CONCLUSIONS: PIM and PIM 2 showed better
      discrimination and calibration than PRISM in a heterogeneous group of children in
      Spanish critical care units. However, these results should be confirmed in a
      larger study.

PMID- 17430711
TI  - [Attitudes and needs of pediatric intensivists in relation to the death of their
      patients].
AB  - INTRODUCTION: Most deaths in infants and children occur in hospitals and
      especially in pediatric and neonatal intensive care units. OBJECTIVES: To
      determine 1) how often pediatric intensivists have to manage dying patients, 2)
      their approach to these patients, and 3) their knowledge of this field and their
      needs. MATERIAL AND METHOD: A 28-item questionnaire was sent by surface mail to
      each physician, as well as another questionnaire with general questions on the
      work of the pediatric intensive care unit (PICU) in 2000. RESULTS: Responses were
      obtained from 20 PICUs (54 %) from different parts of Spain. There where 373
      deaths. More of the half of the deaths (62 %) were due to acute events or
      occurred during the neonatal period. Ninety-four physicians completed the
      questionnaire. Each physician attended four deaths (SD = 3.1; range 0-20). Sixty
      eight percent of the physicians believed that families were helped by knowing the
      possibility that the child might die. Intensivists believed that pediatric
      patients should not be informed that they were dying. In 64 % of deaths, the
      physicians were with their patients at the moment of death. More than half of the
      patients died without physical contact with their parents. Forty-six percent of
      the physicians interpreted death among their patients as a personal or
      professional failure and most (92 %) wanted training. Only three PICUs allowed
      parents to stay all day with their children. CONCLUSIONS: Almost half the
      physicians experienced death as a personal or professional failure and most
      wanted training to help them deal with death in their professional work. Most
      PICUs restrict the time parents are allowed to stay with their children.

PMID- 17430712
TI  - [Prevalence of tobacco use among teenagers and its relation with family
      environment].
AB  - OBJECTIVE: To determine the prevalence of tobacco use among 12-18 year-olds in
      Biscay (Spain) and its relation with the family environment. SUBJECTS AND METHOD:
      We performed a cross-sectional study in 12-18 year-olds. A self-administered,
      anonymous questionnaire was distributed in different schools of the region
      selected by stratified sampling, based on the type of school (public school or
      subsidized private school) and on the linguistic model. The final study sample
      comprised 1921 students. Information was obtained on tobacco, alcohol and other
      drug use, as well as on family and sociodemographic characteristics. RESULTS: A
      total of 51.8 % of the students had used tobacco. One-third (29.9%) of the
      teenagers were current smokers and 50.4% were daily smokers. The mean age of
      first tobacco use was 13.1 +/- 1.85 years. The prevalence of tobacco use was
      higher in girls and increased with age until the age of 15-16 years. More than 90
      % of smokers had experimented with alcohol, 86.3 % had used cannabis at some time
      and 11 % had used other illegal drugs. In multivariate analysis, the variables
      associated with a higher odds of smoking were age, female sex, available money,
      use of other drugs, and smoking by siblings in front of the adolescent.
      CONCLUSIONS: The prevalence of tobacco use among 12-18 year-olds increased in
      relation to female gender, age, having siblings who smoked in their presence,
      available money, and the use of alcohol, cannabis and other illicit drugs.
      Maternal and sibling disapproval of smoking may be associated with lower tobacco
      use among adolescents.

PMID- 17430713
TI  - [Risk factors for the occurrence of sporadic Campylobacter, Salmonella and
      rotavirus diarrhea in preschool children].
AB  - BACKGROUND: Sporadic cases of diarrhea in preschool children are highly frequent,
      especially those caused by rotavirus, Campylobacter and Salmonella. The aim of
      this study was to identify some of the factors associated with these processes.
      MATERIAL AND METHODS: A case-control study of hospitalized incident cases aged
      less than 3 years old was performed. Questionnaires were administered at
      admission, before the results of stool tests were known. Susceptibility, food
      exposure, and environmental factors were investigated. Infants aged less than 1
      year were analyzed separately. RESULTS: A total of 117 patients (rotavirus in 31,
      Campylobacter in 228 and Salmonella in 21, negative results in 37) and 84
      controls were studied. Several protective factors, such as breast feeding and
      prior antibiotic use, were identified. Risk factors for diarrhea were exposure to
      meat products (eating or environmental exposure in the kitchen), some kinds of
      pets, and attendance at day care. Differences were found by etiology and age. In
      the culture-negative group, no risk factors were identified. CONCLUSION: The
      problems posed by epidemiological study of this issue are discussed. The main
      findings in each group of cases are interpreted and proposals are made for their
      application in the control and prevention of these diseases.

PMID- 17430714
TI  - [Factors related to respiratory complications in very low birth weight infants
      with respiratory distress syndrome].
AB  - INTRODUCTION: Very low birth weight (VLBW) infants, with a birth weight below
      1500 g and a structurally immature lung, are at high risk for developing
      bronchopulmonary dysplasia. This risk is even higher if respiratory distress
      syndrome is present. Other acute lung diseases, such as air leak and pulmonary
      hemorrhage, can also be present. The aim of this study was to analyze the
      statistical relevance of several neonatal factors in the development of pulmonary
      complications in a sample of VLBW infants with respiratory distress syndrome.
      PATIENTS AND METHODS: A total of 209 VLBW infants with respiratory distress
      syndrome were studied. The variables analyzed were delivery date, respiratory
      distress syndrome grade, sex, birth weight, gestational age, referral (from
      within the hospital or elsewhere), prenatal corticosteroid administration, type
      of gestation, type of delivery, amniorrhexis time, Apgar test at 1 and 5 minutes,
      surfactant administration, hours of life at which the first dose of surfactant
      was administered, and early sepsis. A multiple logistic regression analysis was
      developed using Hosmer-Lemeshow methodology. RESULTS: In the multivariate
      analysis, air leak was related to respiratory distress syndrome grade and
      surfactant administration. Pulmonary hemorrhage was related to lower birth weight
      and absence of prenatal corticosteroid administration. Bronchopulmonary dysplasia
      was related to single pregnancies, absence of prenatal corticosteroid
      administration, lower birth weight, lower Apgar score at 1 minute, and higher
      respiratory distress syndrome grade. CONCLUSIONS: Respiratory morbidity in VLBW
      infants with respiratory distress syndrome could be influenced by several
      interrelated intrinsic and extrinsic variables.

PMID- 17430715
TI  - [Evaluation of systematic neonatal screening for sickle cell diseases in Madrid
      three years after its introduction].
AB  - BACKGROUND: Sickle cell anemia is a hereditary disease which, as a result of
      migration, constitutes one of the most frequent genetic disorders in northwest
      Europe. Complications secondary to this disease are common during the first 3
      years of life and early diagnosis has been recommended to reduce their
      development. The autonomous community of Madrid began to perform universal
      neonatal screening for hemoglobinopathies in May 2003. This study presents the
      results of the first 32 months of this screening program. METHODS: A prospective,
      descriptive study was designed to include all the neonates born in centers in the
      autonomous community of Madrid from May 2003 to December 2005. A heel prick dried
      blood spot from the Guthrie card was analyzed by high-performance liquid
      chromatography to detect hemoglobin F, A, S, C, D and E. RESULTS: A total of
      190,238 newborns were analyzed, and 1060 hemoglobin variants (5.57 for every 1000
      births) were detected. Thirty-one were sickle cell diseases and appropriate
      antibiotics, vaccination and comprehensive care were initiated. Prenatal
      diagnosis of subsequent pregnancies was performed in three families after
      parental investigation. Carrier parents were from 44 countries of origin.
      CONCLUSIONS: Although sickle cell disease was considered anecdotic in Spain until
      recently, the diagnosis of this entity has markedly increased as a result of
      immigration. The universal screening program is expected to reduce morbidity and
      mortality in the first years of life.

PMID- 17430716
TI  - [Blood glucose and ketone monitoring in type 1 diabetic patients in the
      controlled environment of a summer camp].
AB  - INTRODUCTION: Control of blood ketone levels and glycemia is advisable in certain
      situations in type 1 diabetic children and adolescents. The aims of this study
      were to assess the relationship between glycemia, ketonemia and ketonuria in
      children and adolescents in a summer camp under different conditions (fasting,
      casual hyperglycemia, moderate physical exercise) and to assess the utility of
      ketonemia determinations in diabetes control during this time. PATIENTS AND
      METHODS: There were 47 participants (25 boys and 22 girls), with a mean HbA1c
      determination prior to enrollment of 7.7 +/- 1.5 %. The mean age was 11.7 +/- 1.8
      years and the mean time from onset of diabetes was 3.0 +/- 2.7 years. The mean
      body mass index was 18.3 +/- 3.9 kg/m2 (SDS -0.16 +/- 0.44), the mean insulin
      dose was 0.8 +/- 0.4 U/kg/ day, and the number of doses per day was between 2 and
      4 (median = 3). Blood glucose and ketones (both measured with the Optium system,
      Abbott Diabetes Care) and urine ketones (Ketodiastix, Bayer) were determined in
      different situations. Statistical analysis was performed with the SPSS 11.5
      program. RESULTS: Ketonemia results 45 minutes before and after moderate physical
      activity showed no significant increase in ketones (0.1 +/- 0.03 vs 0.23 +/- 0.07
      mmol/l, ns). Preprandial blood ketone levels of > or = 0.5 mmol/l were found in
      17.02 % of participants. Ketonemia was resolved during the first hour in all
      participants except one, in whom ketonemia resolved in 3 hours. Blood ketones
      were higher before breakfast than during the rest of the day (0.12 +/- 0.17 vs
      0.02 +/- 0.05, p < 0.001). The mean glycemia level with ketosis (beta -HB > or =
      0.5 mmol/l) was 174.5 +/- 64.7 mg/dl, a value slightly higher than the overall
      mean glycemia value (156.87 +/- 87.8 mg/dl). Ketonuria could not be measured in a
      high percentage of participants due to the difficulty of obtaining samples
      (between 24.5 % and 58.6 % in the different study groups). CONCLUSIONS:
      Measurement of glycemia together with ketonemia in a summer camp allows reliable
      follow-up of glycemic control to be performed. Ketonemia usually occurred before
      breakfast in parallel with slightly elevated glycemia, but resolved quickly.
      Moderate physical activity for 45 minutes does not seem to significantly increase
      blood ketones if metabolic control is normal. beta -HB is a useful parameter to
      determine whether moderate physical exercise is advisable or not. The lack of
      urinary ketone tests due to the difficulties of obtaining a sample can currently
      be solved by blood ketone measurement.

PMID- 17430717
TI  - [Respiratory function assessment in cooperative patients. Part I. Spiromery and
      bronchodilator reversibility testing].
AB  - Assessment of respiratory function is the principal tool in the study of patients
      with lung diseases, allowing physiopathological alterations to be detected, and
      the severity of the process, its clinical course, and treatment response to be
      identified. Nowadays, assessment of respiratory function is among the
      investigations used by Spanish pediatricians. The Techniques Group of the Spanish
      Society of Pediatric Pneumology undertook the design of a protocol for the study
      of pulmonary function in children that would incorporate the most recent
      published consensus documents on basic pulmonary function assessment (spirometry
      and bronchodilator reversibility testing) and on airway hyperreactivity
      evaluation using nonspecific provocation tests. The aim of this protocol is to
      provide a guide to good clinical practice until new changes, based on scientific
      evidence, are produced.

PMID- 17430718
TI  - [Skin dimpling: a complication of amniocentesis].
AB  - Second trimester amniocentesis is widely used for the prenatal diagnosis of
      congenital disorders. Direct fetal injury from needle puncture can cause
      cutaneous scarring and rarely leads to severe visceral complications. Before the
      advent of real-time ultrasonography, the incidence of cutaneous lesions after
      amniocentesis ranged from 0.1 % to 9 % in the different series. Few reports of
      cutaneous lesions after amniocentesis have been published since the advent of
      real-time ultrasonography, although the real incidence is unknown. Eight children
      with typical skin dimpling caused by needle puncture during second trimester
      amniocentesis are presented. Current amniocentesis has not completely eliminated
      the risk of needle puncture scarring of the fetus. Dermatologists, pediatricians
      and obstetricians should be aware of this complication, which may have medical
      and legal consequences.

PMID- 17430719
TI  - [Abdominal vascular malformations and Down syndrome].
AB  - Malformations of the abdominal venous system are rare vascular disorders. These
      entities are associated with other malformations and with chromosomal anomalies
      such as trisomy 21. Abdominal venous malformations are probably the most frequent
      congenital vascular malformations in Down syndrome. Prenatal diagnosis allows the
      early follow-up and treatment of complications. We present a case of Down
      syndrome associated with an abdominal venous malformation diagnosed at the first
      trimester of pregnancy.

PMID- 17430720
TI  - [Transitional cell tumor in a 12-year-old patient].
AB  - Transitional cell papillomas, which are tumors of epithelial origin, are the most
      common urinary tract neoplasm in adults but are extremely rare in children. In
      both groups the main location is the bladder, often around one of the ureteric
      orifices. Symptoms vary widely but the most frequent is gross hematuria.
      Transitional cell papillomas are histologically low-grade tumors and total
      excision is considered curative. However the rate of recurrence in the literature
      is high, and there is a potential for a more aggressive type of tumor. We report
      the case of a 12-year-old girl who presented with a transitional cell papilloma
      near the right ureteric orifice and describe the etiopathogenesis, diagnosis,
      treatment and outcome of this entity.

PMID- 17430721
TI  - [Lemierre's syndrome].

PMID- 17430722
TI  - [Atypical cat scratch disease in an immunocompetent school-aged child].

PMID- 17430723
TI  - [Comorbidity in malaria in the pediatric population].

PMID- 17430724
TI  - [Shagreen patches].

PMID- 17430725
TI  - [Juvenile myasthenia gravis. An overlooked disease by pediatricians].

PMID- 17430726
TI  - [Adverse drug reaction as the form of onset of egg sensitization].

PMID- 17430727
TI  - [Torticollis secondary to atlantoaxial rotatory subluxation].

PMID- 17430728
TI  - [The Hermes Research Group: evaluation of dietary exposure to methylmercury in
      vulnerable populations in the region of Murcia (Spain)].

PMID- 17430729
TI  - [Alterations in cutaneous pigmentation associated with intestinal obstruction].

PMID- 17430730
TI  - [Sudden lameness in an afebrile infant].

PMID- 17430731
TI  - Asymmetric lateral distribution of obstructed hemivagina and renal agenesis in
      women with uterus didelphys: institutional case series and a systematic
      literature review.
AB  - OBJECTIVE: To investigate if an asymmetry exists in the lateral distribution of
      obstructed hemivagina and renal agenesis in women with uterus didelphys. DESIGN:
      All English-language medical papers on uterus didelphys, obstructed hemivagina,
      and associated renal agenesis published from 1980 to 2005 and identified by
      Embase, Medline, and Pubmed database searches were retrieved. In addition, 41
      institutional cases are described. We considered articles in which the presence
      of a uterus didelphys, obstructed hemivagina, and renal agenesis was assessed as
      well as the affected side. Data were stratified based on surgical confirmation or
      imaging evidence of the specific mullerian anomaly. Two authors abstracted data
      independently on standardized forms, and the combined frequency of right- and
      left-side malformation subtype was computed. RESULT(S): Thirty-six reports
      including 138 subjects were selected. Unilateral hemato- or pyocolpos was on the
      right side in 91 patients (66%). Among the 125 cases with surgical demonstration
      of the mullerian malformation subtype, 81 (65%) had the anomaly on the right
      side. In the institutional series, lesions were on the right side in 25 cases
      (61%). Combining the above figures, the observed proportion of right-sided
      anomalies (116/179) was 65% (95% CI 57% to 72%). CONCLUSION(S): Left-right
      asymmetry may be induced before organogenesis, establishing differences in
      morphogenesis on the left and right sides of the embryo.

PMID- 17430732
TI  - Etiology, symptomatology, and diagnosis of uterine myomas.
AB  - OBJECTIVE: To review the currently available literature regarding the biology,
      etiology, symptoms, and diagnosis of uterine myomas. DESIGN: Literature review of
      220 articles pertaining to uterine myomas. RESULT(S): Although uterine myomas
      presently are not well understood, many advances have been made in the
      understanding of the hormonal factors, genetic factors, growth factors, and
      molecular biology of these benign tumors. Prospective, longitudinal studies are
      underway to characterize the risk factors for their development. When needed, the
      position of myomas can be best imaged by sonohysterography or magnetic resonance
      imaging. Evidence suggests that only submucous myomas appear to interfere with
      fertility, and only very rarely do myomas effect pregnancy outcome.
      CONCLUSION(S): A summary of the available literature regarding the biology,
      etiology, symptomatology, and diagnosis of myomas shows that, although they are
      still not well understood, much has been learned about uterine myomas.

PMID- 17430733
TI  - Role for tumor necrosis factor alpha (TNF-alpha) and interleukin 1-beta (IL
      1beta) determination in seminal plasma during infertility investigation.
AB  - OBJECTIVE: To evaluate the clinical relevance of tumor necrosis factor alpha (TNF
      alpha) and interleukin 1-beta (IL-1beta) determination in seminal plasma during
      infertility investigation. DESIGN: Prospective study. SETTING: Outpatient
      infertility clinic of a university-based hospital. PATIENT(S): Randomly chosen
      asymptomatic males (n = 148) from subfertile couples. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Determination of TNF-alpha and IL-1beta in seminal plasma
      (SP) by enzyme-linked immunosorbent assay (ELISA). In aliquots of the same
      ejaculates: 1) evaluation of semen quality with sperm analysis and sperm function
      testing; 2) determination of antisperm antibodies (ASA) of the immunoglobulin
      (Ig) G and IgA class; 3) microbial screening; and 4) immunocytochemical round
      cell differentiation to determine leukocyte counts and ratios. Medical history,
      clinical examination, and determination of subsequent fertility (after control
      for female infertility factors). RESULT(S): The concentrations of TNF-alpha and
      IL-1beta in SP correlated significantly (r = 0.65; P<.0001), and these parameters
      were significantly related to the leukocyte ratio (%LC) of the seminal round
      cells (r = 0.36; P<.001) and the leukocyte counts per ejaculate (r = 0.34;
      P<.001). There was no relationship of TNF-alpha and IL-1beta levels in SP with
      semen quality or parameters of sperm functional capacity, and there was no
      association with local ASA of the IgG or IgA class. The concentration of both
      cytokines was also not related to the outcome of the microbial screening and did
      not affect subsequent fertility. No correlation of TNF-alpha and IL-1beta levels
      in SP with the concentration of C-reactive protein in same-day serum samples was
      found. CONCLUSION(S): The levels of TNF-alpha and IL-1beta in seminal fluid
      correlate significantly with leukocyte counts and ratios in the same ejaculates,
      as indicators of silent male genital tract infection/inflammation. However, this
      is not related to semen cultures in asymptomatic individuals and not associated
      with clinically relevant parameters of semen quality, including sperm fertilizing
      capacity.

PMID- 17430734
TI  - Effects of a supplement containing isoflavones and Actaea racemosa L. on
      asymmetric dimethylarginine, lipids, and C-reactive protein in menopausal women.
AB  - OBJECTIVE: To investigate the effects of a supplement containing soy isoflavones
      and Actaea racemosa L. on several coronary heart disease (CHD) risk markers in
      menopausal women. DESIGN: Randomized, placebo-controlled, double-blind study.
      SETTING: Nine hospitals in The Netherlands. PATIENT(S): One hundred twenty-four
      menopausal women. INTERVENTION(S): Daily placebo (n = 64) or supplement
      containing soy isoflavones and Actaea racemosa L. (n = 60) for 12 weeks. MAIN
      OUTCOME MEASURE(S): Fasting blood concentrations of asymmetric dimethylarginine
      (ADMA), lipids, and C-reactive protein (CRP) at baseline and week 12. RESULT(S):
      In the supplement group, total cholesterol and low-density lipoprotein
      cholesterol showed a small absolute reduction at week 12 (-0.2, 95% confidence
      interval [CI] -0.3 to -0.0; and -0.2, 95% CI -0.3 to -0.0; respectively).
      Concentrations of ADMA, triglycerides, lipoprotein(a), and CRP did not change
      significantly. Analysis of covariance over the 12-week study period revealed no
      significant between-group differences for all parameters. No significant
      correlations were found between the concentrations of isoflavones and the CHD
      risk markers investigated. CONCLUSION(S): Twelve-week administration of a
      supplement containing soy isoflavones and Actaea racemosa L. had little or no
      influence on the CHD risk markers studied. This supplement probably has neither
      protective nor adverse effects on the cardiovascular system; however, large long
      term studies are needed to test this.

PMID- 17430735
TI  - Extinction of FOXL2 expression in aggressive ovarian granulosa cell tumors in
      children.
AB  - OBJECTIVE: In the female gonad, FOXL2 is a key factor for proper differentiation
      of granulosa cells (GC) during folliculogenesis and its expression persists in
      the ovary after birth. The aim of this multicentric nationwide study was to
      determine whether FOXL2 expression varies during tumoral proliferation of GC
      cells in juvenile ovarian GC tumors (OGCT). DESIGN: Nationwide retrospective
      study. SETTING: University Hospital of Montpellier, Department of Hormonology.
      PATIENT(S): Between 1994 and 2004, 26 patients with juvenile OGCT were reported
      in the TGM95 database of the French Society for Childhood Cancer (SFCE) and from
      eight pediatric endocrinology centers. Immunohistochemistry was performed using
      an anti-FOXL2 antibody. INTERVENTION(S): Immunohistochemistry studies of FOXL2 on
      OGCT slides. MAIN OUTCOME MEASURE(S): Level of FOXL2 expression within the tumor,
      International Federation of Gynecology and Obstetrics classification, and tumor
      recurrences. RESULT(S): FOXL2 expression was absent in the GC of 10 patients and
      was markedly reduced in the cells of 4 patients. Precocious pseudopuberty was
      more frequently the revealing symptom in the children with conserved FOXL2
      expression. Patients with no or reduced expression of FOXL2 more frequently
      exhibited associated hemorrhagic ascites, higher mitotic activity in the tumor,
      and significantly more advanced oncologic staging. All patients requiring
      complementary treatment (n = 7; chemotherapy or complementary surgery) had
      reduced expression of FOXL2 in the tumor. All recurring OGCT exhibited a complete
      extinction of FOXL2 expression (n = 3). CONCLUSION(S): These results show that
      FOXL2 is not expressed or is underexpressed in juvenile OGCT with an aggressive
      pattern of progression, and it thus may be a prognostic factor for these tumors.

PMID- 17430737
TI  - Acupuncture and IVF Controversies.

PMID- 17430736
TI  - Early follicular progesterone concentrations and in vitro fertilization pregnancy
      outcomes.
AB  - In IVF cycles using a GnRH agonist down-regulation short protocol, when the
      concentration of P on day 4 of stimulation was >3 ng/mL, patients experienced a
      significantly reduced implantation rate (14.1%), pregnancy rate (24.6%), and
      ongoing pregnancy rate (20.0%), with an elevated early miscarriage rate (18.8%).

PMID- 17430740
TI  - A call to all nurses working in geriatrics: make 2007 a great year by joining the
      campaign: Advancing Excellence in America's Nursing Homes.

PMID- 17430741
TI  - Antidepressant tapering: avoiding adverse consequences of gradual dose reduction.

PMID- 17430742
TI  - Handling difficult family situations: practical approaches.

PMID- 17430743
TI  - Assisted living nursing practice: medication management: Part 1. Assessing the
      resident for self-medication ability.
AB  - Self-administration of medication suggests that individuals are functionally and
      cognitively competent to manage their health care. Older adults take a
      significant number of medications (borderline polypharmacy) as well as an
      unaccounted for number of over-the-counter, as necessary, and herbal remedies.
      Assisted living residences, moving from a social to a more medical model, are
      responsible for the safety and well-being of their residents. In addition, the
      prospect of aging-in-place in the residence is increasingly associated with
      appropriate medical and medication management. Assisted living services in most
      states include assistance with medication, but the nature of the assistance
      varies widely, at times approaching what even a nonclinical observer would regard
      as medication administration. Although state assisted living regulations can be
      quite specific regarding medication storage, there are scant guidelines about the
      components of a thorough assessment as to whether a resident can safely self
      administer his or her medications. This article discusses assessment criteria of
      self-medication ability, drawn from a variety of instruments. In keeping with
      assisted living nursing standards of practice, the assisted living nurse has a
      critical responsibility in assessment of this self-care ability.

PMID- 17430744
TI  - Pilot study of the feasibility and effectiveness of a natural laxative mixture.
AB  - We sought to determine the effect of a natural laxative mixture compared with
      daily prescribed laxatives on bowel movement frequency in elderly long-term care
      residents. Secondary endpoints included ease of administration and costs of the
      natural laxative. A randomized controlled trial comparing the effect of the
      Beverley-Travis natural laxative mixture to prescribed laxatives was conducted
      over an 8-week period. Subjects were randomized to treatment and control groups;
      control subjects continued on regularly prescribed laxatives, and treatment group
      subjects discontinued prescribed laxatives and received 2 tablespoons of the
      natural laxative mixture twice a day for the remaining 4-week period. Bowel
      movement frequency and consistency were collected, and ease of natural laxative
      administration as well as costs associated with use of the natural or prescribed
      laxatives were calculated. The study included 45 residents, with 34 completing
      the 8-week study period (16 treatment group subjects and 18 control subjects).
      Treatment group subjects had a significant increase in average number of bowel
      movements from 15.5 to 22.2 (P = .007) following initiation of the natural
      laxative, and no difference in bowel movement frequency was observed among
      control subjects (P = NS). The natural laxative mixture was rated as "easy" or
      "very easy" to administer by 90%-92% of nurses, and cost savings of $103.04 was
      estimated. The Beverley-Travis natural laxative mixture, given at a dosage of 2
      tablespoons twice daily, is easy to use, cost-effective, and more effective than
      daily prescribed laxatives at producing normal bowel movements.

PMID- 17430745
TI  - Aging, health, and physical activity in Korean Americans.
AB  - Little is known about the health benefits and the factors that influence physical
      activity among older adults from ethnically different backgrounds. The aim of
      this article is to provide a sociocultural context for understanding aging,
      health, and physical activity among older Korean Americans. Studies that focused
      on physical activity and exercise among older adults, older Koreans, or older
      Korean Americans were reviewed. The results of the review were integrated to
      better understand physical activity in older Korean Americans. Results from
      varied population-based, cross-sectional, and longitudinal studies that assessed
      the relationships among aging, health, and physical activity were relatively
      consistent in their findings. Many correlational studies found a strong, positive
      relationship between physical activity and health benefits and a moderately
      positive but sometimes mixed association between physical activity and quality of
      life among older adults. Additional research is needed to clarify the gap between
      physical activity and actual and predictive quality of life among older Korean
      Americans. Also, we need more evidences to show the effects of late-life physical
      activity or exercise on reducing or minimizing disablement in older Korean
      Americans.

PMID- 17430746
TI  - Be a continence champion: use the CHAMMP tool to individualize the plan of care.
AB  - In June 2005, the U.S. Centers for Medicare and Medicaid Services (CMS) issued
      revised guidance to surveyors for Section 483.25(d), Urinary Incontinence, Tag
      F315. Part 1 instructs that an indwelling catheter not be used without valid
      medical justification. Part 2 requires that a resident receive treatment to
      restore continence to the extent possible. Identification, assessment, and
      diagnosis of incontinence are crucial to preparing an individualized plan of care
      for treatment. Many articles discuss treatment protocols, but they do not focus
      on identification and assessment of the incontinent resident. The CHAMMP
      (Continence, History, Assessment, Medications, Mobility, Plan) Tool provides a
      comprehensive evaluation tool that incorporates information from the resident and
      provides the documentation necessary for the MDS (Minimum Data Set) and RAP
      (Resident Assessment Protocol) assessment process. It is used to establish an
      individualized plan of care.

PMID- 17430747
TI  - Assessment of safety attitudes in a skilled nursing facility.
AB  - Safety has not been well studied in the long-term care setting. This pilot study
      assesses staff attitudes regarding safety culture at one 250-bed skilled nursing
      facility. A valid and reliable Safety Attitudes Questionnaire (SAQ) was
      administered once to a sample of 51 employees. Nursing staff and other health
      care staff were generally satisfied with their jobs (42% and 67% had a positive
      attitude, respectively) but gave low scores to Management (22% and 13%,
      respectively) and Safety Climate (28% and 33%, respectively). Registered nurses,
      licensed practical nurses, and nurse management/supervisors received the highest
      ratings for quality of collaboration and communication (range: 3.6-4.1 on a 5
      point Likert scale with 1 = very low, 5 = very high), whereas nurse practitioners
      and physician assistants received the lowest (range: 2.5-2.9). The SAQ provided
      insight into employees' safety attitudes and can be used to identify
      opportunities for improvements in safety.

PMID- 17430750
TI  - Anti-inflammatory activity of tetracyclines.
AB  - Tetracyclines are known to exhibit multiple significant anti-inflammatory
      actions. This article describes the mechanisms of this anti-inflammatory
      activity, such as inhibition of chemotaxis, granuloma formation, and protease.
      The article also discusses the effectiveness of tetracyclines in treating such
      diseases as acne vulgaris, rosacea, bullous dermatoses, granulomatous disease,
      and livedo vasculitis.

PMID- 17430749
TI  - Status report on antibiotic resistance: implications for the dermatologist.
AB  - In the United States and worldwide, public awareness of the progressive rise in
      antibiotic resistance has increased among public health officials, the medical
      community, and the lay public. The common use of systemic antibiotic therapy in
      dermatology warrants a closer look at how prescribing patterns impact on the
      development of antibiotic resistant bacteria and outcomes in clinical practice.

PMID- 17430751
TI  - Pharmacologic modulation of sebaceous gland activity: mechanisms and clinical
      applications.
AB  - Acne vulgaris is a common skin condition seen by physicians. It primarily affects
      adolescents, but can continue into adulthood. A key factor in the pathogenesis of
      acne is sebum production. Typical therapy includes combinations of topical
      retinoids and antimicrobials for mild acne, with the addition of oral antibiotics
      for moderate to severe disease. In the most recalcitrant cases or for
      nodulocystic acne, oral retinoids are indicated. In women who fail to respond to
      conventional treatment, hormonal therapy is often used adjunctively. Only
      isotretinoin and hormonal therapy improve acne via their action on the sebaceous
      glands. This article focuses on the mechanisms by which these treatment
      modalities act on the sebaceous glands and their clinical use in the practice of
      medicine.

PMID- 17430752
TI  - Topical immunomodulation: modes of action with clinical correlation.
AB  - Many classes and preparations of immunomodulators are available to the clinician,
      serving as stimulatory or inhibitory influences on a variety of disease states.
      To maximize their efficacy, it is important for the clinician to take a step back
      from the usual routine of treating symptoms and consider the immune processes
      that took place to create inflammation, tumors, or responses to infections. From
      there, after considering the short-term and long-term consequences of the
      treatment, one can match the immune profile of the disease to the treatment. Most
      importantly, immunomodulators provide the opportunity to do what is best for the
      patient at that time, as well as for control of the future of the disease,
      whether it is acute or chronic.

PMID- 17430753
TI  - Methicillin-sensitive and methicillin-resistant Staphylococcus aureus: management
      principles and selection of antibiotic therapy.
AB  - Strains of community-acquired Methicillin-resistant Staphylococcus aureus (CA
      MRSA) have emerged as an important group of pathogens. Most infections present as
      cutaneous abscess and most of these may respond to drainage alone. Sulfonamide
      and tetracycline antibiotics remain valuable agents for most CA-MRSA infections,
      but inducible resistance to clindamycin is problematic in some areas. Linezolid,
      and the newer parenteral antibiotics should be reserved for serious infections.

PMID- 17430754
TI  - Advances in topical and systemic antifungals.
AB  - Topical antifungal agents are generally used for the treatment of superficial
      fungal infections unless the infection is widespread, involves an extensive area,
      or is resistant to initial therapy. Systemic antifungals are often reserved for
      the treatment of onychomycosis, tinea capitis, superficial and systemic
      candidiasis, and prophylaxis and treatment of invasive fungal infections. With
      the development of resistant fungi strains and the increased incidence of life
      threatening invasive fungal infections in immunocompromised patients, some
      previously effective traditional antifungal agents are subject to limitations
      including multidrug interactions, severe adverse effects, and their fungistatic
      mechanism of actions. Several new antifungal agents have demonstrated significant
      therapeutic benefits and have broadened clinicians' choices in the treatment of
      superficial and systemic invasive fungal infections.

PMID- 17430755
TI  - Systemic retinoid therapy: a status report on optimal use and safety of long-term
      therapy.
AB  - Systemic retinoids are an important component of the dermatology treatment
      armamentarium offering unique therapeutic properties, and are widely used to
      treat a large spectrum of skin disorders. Rational selection of candidates for
      treatment, knowledge regarding appropriate and optimal use, awareness of common
      and uncommon potential adverse reactions, and proper use of clinical and
      laboratory monitoring can result in effective and safe treatment of several
      severe skin disorders that impact poorly on the overall health and quality of
      life of affected patients.

PMID- 17430756
TI  - Suggested guidelines for patient monitoring: hepatic and hematologic toxicity
      attributable to systemic dermatologic drugs.
AB  - Hepatic and hematologic toxicity are among the most fearful adverse effects that
      occasionally occur as a result of systemic drugs in the dermatologist's
      therapeutic armamentarium. Drugs of greatest interest concerning hepatic toxicity
      include methotrexate, azathioprine, dapsone, and acitretin. Somewhat overlapping
      are drugs that have important hematologic toxicities, including methotrexate,
      azathioprine, dapsone, sulfonamides, cyclophosphamide, and chlorambucil.
      Laboratory tests most commonly used include (1) hepatic monitoring: transaminases
      (AST/SGOT and ALT/SGPT) and the ultrasound-guided liver biopsy, and (2)
      hematologic monitoring: CBC with diff and platelets along with occasional use of
      the reticulocyte count. Important principles and specific guidelines for
      monitoring by drug group are highlighted.

PMID- 17430757
TI  - Potential complications associated with the use of biologic agents for psoriasis.
AB  - The biologic agents are effective drugs to treat psoriasis. They provide
      physicians with additional options for patients who cannot tolerate traditional
      therapies or for whom traditional therapies are not sufficient. While these new
      TNF-alpha inhibitors and anti-T-cell agents have potential complications, they
      are generally safe with proper monitoring. Both physicians and patients should be
      aware of the risks involved with each medicine so that the correct drug is chosen
      to suit each patient.

PMID- 17430758
TI  - Drug reactions affecting the nail unit: diagnosis and management.
AB  - Several drugs may be responsible for the development of nail abnormalities, but
      only a few classes are consistently associated with nail symptoms. Drug-induced
      nail abnormalities result from toxicity to the matrix, the nail bed, the
      periungual tissues, or the digit blood vessels. Pharmacologic agents that most
      frequently produce nail abnormalities include retinoids, indinavir, and cancer
      chemotherapeutic agents.

PMID- 17430759
TI  - Drug reactions affecting hair: diagnosis.
AB  - Drugs may cause hair loss, stimulate hair growth, or induce changes in the hair
      shape and color. Drug-induced hair loss is, in most cases, a consequence of a
      toxic effect of the drug on the hair matrix. Although a large number of drugs
      have been occasionally reported to produce hair loss, the relationship between
      drug intake and hair loss has been proven only for a few agents. Type of hair
      loss (telogen effluvium, anagen effluvium, or both) depends on the drug, its
      dosage, and patient's susceptibility. Drug-induced hair loss is usually
      reversible.

PMID- 17430760
TI  - Drug-associated lymphoma and pseudolymphoma: recognition and management.
AB  - This article discusses ways to recognize and manage lymphomas and pseudolymphomas
      associated with drug exposure. Over the last 30 years, the classification of
      pseudolymphomas and lymphomas has undergone significant change, especially
      following the application of sophisticated immunostaining and gene rearrangement
      analysis. The term cutaneous pseudolymphomas (CPL) is a nonspecific term for a
      heterogeneous group of benign reactive T- or B-cell lymphoproliferative processes
      that simulate cutaneous lymphomas clinically or histologically. While
      pseudolymphomas are relatively rare diseases, their clinical and histological
      heterogeneity has led to multiple systems of categorization based on
      immunological factors, causative agents, presentation, and clinical course.

PMID- 17430761
TI  - Recognition and management of severe cutaneous drug reactions.
AB  - Cutaneous drug reactions are among the most common types of adverse drug
      reactions. This article focuses on the recognition and management of severe
      cutaneous drug eruptions, including the drug-hypersensitivity syndrome, serum
      sickness-like reaction, acute generalized exanthematous pustulosis, Stevens
      Johnson syndrome, and toxic epidermal necrolysis. Cutaneous reactions are
      considered severe when they can result in serious skin damage or involve multiple
      organs. Some of these reactions can cause significant morbidity or death. Each
      may be confounded by diagnostic difficulties, confusion in ascertaining
      causality, and treatment challenges.

PMID- 17430762
TI  - Newly recognized cutaneous drug eruptions.
AB  - Many new drugs are entering the marketplace and although some cutaneous reactions
      might be noted in the preclinical evaluation, some of the reactions, particularly
      those that are rare, will not be noted until the drugs enter widespread use. In
      addition, distinctive reactions may occur, as is the case with epidermal growth
      factor-receptor inhibitors. Careful observation and evaluation might result in a
      better understanding of "naturally" occurring skin disease.

PMID- 17430765
TI  - Medical management of the athlete: evaluation and treatment of important issues
      in sports medicine.
AB  - Providing care to athletes involves much more than simply treating
      musculoskeletal injuries. Many of the illnesses and disease processes that affect
      the general population are also seen in competitive athletes. Medical management
      of these conditions, however, can be challenging. Treatment plans need to be
      tailored to the individual athlete and take into consideration the rigors and
      demands of his or her particular sport. Important conditions that all physicians
      who provide care for athletes should be familiar with are sudden cardiac death,
      hypertension, concussion, methicillin-resistant Staphylococcus aureus infections,
      the female athlete triad, diabetes mellitus, and asthma.

PMID- 17430766
TI  - Diabetes: the latest trends in glycemic control.
AB  - The increasing pervasiveness of diabetes mellitus on a global stage has been well
      documented. Many groundbreaking studies have detailed the consequences of
      inadequate glycemic control, but only recently have data supported evidence that
      demonstrates benefits in the acute setting. Consensus is lacking with regard to
      how to achieve glycemic control in the hospital setting. This article discusses
      glycemic control, with special emphasis on the perioperative patient. Emerging
      therapeutic treatments and less frequently encountered protocols such as insulin
      pump management and insulin infusion are considered.

PMID- 17430767
TI  - Obesity and considerations in the bariatric surgery patient.
AB  - Morbid obesity is a worldwide pandemic. Medical problems associated with being
      obese include hypertension, diabetes, pulmonary restrictive disease, obstructive
      sleep apnea, and increased risk of cancer. In addition, there is a tremendous
      financial burden on society and the health care system to take care of these
      individuals. Bariatric surgery has proved to be a safe, effective means of
      sustained weight loss, which can lead to improvement or resolution of obesity
      related medical conditions. Individuals who are morbidly obese represent a unique
      population requiring special consideration when presenting for medical care.

PMID- 17430768
TI  - Perioperative management of the podiatric surgical patient.
AB  - Advanced thought and planning are required when preparing for podiatric surgery.
      In addition to appropriate procedure selection and follow-up, perioperative
      management has a key role in patient and physician satisfaction. Neglect of this
      aspect of podiatric care can also be a source of malpractice. This article
      analyzes many of the common medical treatments currently employed and makes
      recommendations for treatment before, during, and after surgery.

PMID- 17430769
TI  - Perioperative nutrition and the use of nutritional supplements.
AB  - The poor dietary habits and aging of the US population have caused a steady
      increase in the incidence of chronic disease. The prevalence of these diseases,
      such as obesity, diabetes, and heart disease, may have a significant effect on
      perioperative management, surgical outcome, and complication rates in these
      patients. Nutritional intervention and supplementation may help curb some of
      these potential adverse affects of poor nutrition by promoting wound healing;
      enhancing immunity; reducing swelling, bruising, and inflammation; and reducing
      oxidation caused by anesthetic agents and surgery. Although a perioperative
      regimen of dietary supplements may enhance surgical outcomes, it is equally
      important to know the popular herbal products that are contraindicated in the
      perioperative period.

PMID- 17430770
TI  - Evaluating and minimizing cardiac risk in surgical patients.
AB  - Cardiovascular complications are a major cause of postoperative morbidity and
      mortality. Proper assessment of risk and subsequent interventions can help
      diminish these complications. Assessing the patient's risk is based on the type
      of surgery performed and on individual patient characteristics. The latter can be
      established with a thorough history and physical, laboratory testing, risk
      indices, and cardiology studies.

PMID- 17430771
TI  - An infectious disease update on antibiotics: emerging resistance.
AB  - Podiatric physicians often encounter infectious processes in the lower extremity
      in inpatient and outpatient settings. Bacterial resistance to antibiotics is a
      growing concern for clinicians treating these infections, especially in complex
      patients who have immune compromise such as diabetes. Although a number of
      antibiotic options are available for the treatment of lower-extremity soft tissue
      and bone infections, a careful examination of bacterial susceptibilities, drug
      resistance, and treatment efficacy can result in better patient care and limb
      salvage.

PMID- 17430772
TI  - Osteoporosis: pathogenesis, new therapies and surgical implications.
AB  - Many developments occurred in the realm of bone healing in recent years. Genetic
      discoveries, new proteins affecting bone health, and new treatments have steered
      our treatment of traumatic and iatrogenic fractures in new directions.
      Osteoporosis strikes many subsets of the world population, including: women, the
      elderly, and those suffering from arthritis, autoimmune diseases, HIV, and the
      immunocompromised. This disease predisposes people to an increased risk of low
      trauma and fragility fractures. The baby boomer generation and an increasing
      lifespan may burden the economy by creating such a large group susceptible to
      such a potentially devastating disease. The novel treatments and coping with the
      potentially challenging surgical implications will aide the podiatric physician
      in both medical and surgical management of osteoporosis.

PMID- 17430773
TI  - Concepts in pain management.
AB  - Pain has become an increasingly recognized symptom that plays a major role in the
      treatment of many podiatric patients. Management of this now accepted fifth vital
      sign can be accomplished through many avenues. Nonsteroidal anti-inflammatory
      medications and short- and long-acting opioids are typically used by many
      podiatric physicians; however, the benefits and potential hazards of other
      pharmaceutic approaches using antidepressants, anticonvulsants, topical
      medications, and other centrally acting medications must also be recognized. In
      addition, the role of the psychiatrist or therapist should not be neglected
      because many types of cognitive therapies are available to aid in treating these
      patients.

PMID- 17430774
TI  - The role of the Na(+)/Ca(2+) exchanger (NCX) in neurons following ischaemia.
AB  - The Na(+)/Ca(2+) exchanger (NCX) is a bi-directional membrane ion transporter.
      Under normal conditions, the exchanger transports one calcium ion out of the cell
      and three sodium ions into the cell. This is known as the calcium exit, or
      "forward" mode. Under certain conditions, however, the exchanger can reverse and
      transport calcium ions into the cell (calcium entry mode). Because dysregulation
      of sodium and calcium homeostasis is an integral feature of ischaemic brain
      injury, the role of the NCX in neurons following ischaemia has been investigated
      using a number of in vitro and in vivo models. Studies using in vitro ischaemia
      related models (hypoxia, glutamate) have produced conflicting results, with some
      showing that NCX activity is neuroprotective while others indicate that it is
      neurodamaging. The majority of in vivo studies using the focal cerebral ischaemia
      model indicate that blocking NCX activity is neurodamaging while increasing NCX
      activity is neuroprotective. We have reviewed the major in vitro and in vivo
      neuronal ischaemia-related NCX studies in an attempt to clarify the reason for
      the conflicting findings. The use of different ischaemia models and doubts as to
      the specificity of pharmacological NCX inhibitors and stimulators has contributed
      to the confusion over the role of the NCX in ischaemic brain injury. The
      development of NCX transgenic animals may help our understanding of the role of
      this ion exchanger in neurons following ischaemia and aid the development of an
      effective stroke treatment.

PMID- 17430775
TI  - Complications related to positioning in posterior fossa craniectomy.
AB  - To compare complications associated with surgical position, a retrospective study
      was conducted on 260 patients who underwent posterior fossa craniectomy. Data
      collected from the records included demographic profile, American Society of
      Anesthesiologists' physical status score, neurological status, cranial nerve
      involvement, associated medical illnesses, anaesthetic technique, patient
      position, haemodynamic changes, duration of surgery, venous air embolism (VAE),
      blood loss/transfusion, postoperative complications, duration of ICU stay, and
      postoperative neurological status. Statistical analysis was done using the Chi
      square test and independent t-tests. The demographic profile and preoperative
      associated medical illnesses of patients were comparable between groups. The
      incidence of end-tidal carbon dioxide (EtCO2) detected VAE was more (p=0.00) in
      the sitting position than the horizontal positions (15.2% vs. 1.4%). Blood
      loss/transfusion and the duration of surgery were significantly higher in the
      horizontal position (p<0.05). Brainstem handling was the most common cause of
      prolonged postoperative mechanical ventilation and was seen more in the sitting
      position. Lower cranial nerve functions were preserved better in the sitting
      position (p<0.05). Most postoperative complications (surgical or otherwise) were
      comparable between the groups (p>0.05). Most patients in both groups developed
      mild-to-moderate disability with independent lifestyle at the seventh
      postoperative day. To conclude, both sitting and horizontal positions can be used
      safely in posterior fossa surgeries.

PMID- 17430776
TI  - Reduction in shunt infection using antibiotic impregnated CSF shunt catheters: an
      Australian prospective study.
AB  - Antibiotic impregnated shunt catheters have emerged as a promising tool against
      the continuing challenge of shunt infection. We present our prospective
      evaluation of the efficacy of antibiotic (rifampicin and clindamycin) impregnated
      cerebrospinal fluid (CSF) shunt catheters (AIC) in a mixed paediatric and adult
      Australian population. We have prospectively evaluated all the cerebrospinal
      fluid shunt procedures carried out in our institution over a 3-year period since
      July 2002, after the introduction of AIC in our practice. Patient demographics,
      indication for shunt procedure, risk factors for infection, shunt infections and
      other relevant factors were documented. The data has been compared with similar
      data collected over the previous 7 years of our experience with non-antibiotic
      impregnated catheters for CSF shunt procedures. Pearson's chi-square and Fisher's
      exact tests are used for statistical evaluation. From July 2002 to June 2005, 243
      shunt procedures were carried out using AICs in 178 patients. There were three
      shunt infections (1.2%). Rigorous retrospective evaluation of shunt procedures
      over the preceding 7 years revealed 36 infections in 551 shunt procedures (6.5%).
      This reduction in the infection rate was statistically significant (p=0.0015 on
      Pearson's chi-square test and p=0.000529 on Fisher's exact test). We also report
      that the introduction of ceftriaxone prophylaxis during this period was
      associated with a reduction in Gram-negative shunt infection, but no effect on
      overall infection rate. We report rifampicin and clindamycin impregnated CSF
      shunt catheters significantly reduce the rate of shunt infection in Australian
      clinical practice. This data and the literature support the routine usage of AIC
      for all CSF shunt procedures.

PMID- 17430777
TI  - The cost of multiple sclerosis in Australia.
AB  - Multiple sclerosis (MS) represents a significant economic burden both to the
      patient and to society. This study aims to provide information about direct and
      indirect costs of MS in Australia. Detailed questionnaires were completed for 100
      patients over a 6-month period (12 months for hospitalization costs). Overall,
      the average annual direct and indirect costs per patient were AU$20 396 and AU$15
      085, respectively. The greatest uses of resources were for immunomodulating
      drugs, consultations and district nursing. Various factors significantly
      increased overall direct costs, including secondary progressive MS, severe MS
      symptoms and higher Expanded Disability Status Scale scores. This study confirms
      that MS is a costly disease with a high economic burden on society. In order to
      minimize MS costs and improve quality of life, the ideal aim of MS treatment
      should be to stabilize patients on a low disability (low cost) level at an early
      stage of the disease utilising a cost-effective therapy.

PMID- 17430778
TI  - Increased apoptosis and cysteinyl aspartate specific protease-3 gene expression
      in human intracranial aneurysm.
AB  - OBJECTIVE: To investigate apoptosis in vascular smooth muscle cells (VSMCs) and
      caspase-3 expression in ruptured intracranial aneurysm. METHODS: Tissue samples
      of 15 ruptured intracranial aneurysms, 6 abdominal aortic aneurysms (AAA) and 6
      normal vessels were evaluated. Apoptosis in VSMCs was determined on transmission
      electron microscopy. Immunohistochemistry for alpha-SMC actin and direct cell
      counts (medial VSMCs per high-power field (HPF)) were employed to determine
      medial VSMC density. Additionally, gene expression of caspase-3 was determined
      using real-time RT-PCR. RESULTS: We demonstrated medial VSMCs exhibiting
      morphological apoptotic changes in cerebral aneurysm and AAA. Medial VSMC density
      was significantly decreased in intracranial aneurysm (43.9+/-4.3 SMCs/HPF) and
      AAA (53.2+/-9.4 SMCs/HPF) compared with the normal arteries (222.8+/-12.1
      SMCs/HPF; p<0.01). An 8.94-fold and 6.73-fold increase in expression of caspase
      3mRNA in intracranial aneurysm and AAA, respectively, were obtained relative to
      the normal vessels. CONCLUSIONS: These results suggest that real time RT-PCR
      provides a useful tool to test gene expression in small samples, and may
      contribute to a better understanding of the role of apoptosis in ruptured
      intracranial aneurysm.

PMID- 17430779
TI  - Intracisternal versus intracarotid infusion of L-arginine in experimental
      cerebral vasospasm.
AB  - AIM: The effect of short term intracisternal and intracarotid L-arginine infusion
      on experimental cerebral acute phase vasospasm in a rabbit subarachnoid
      haemorrhage model is investigated, and the two groups compared. MATERIALS AND
      METHOD: Subarachnoid haemorrhage was produced by intracisternal injection of
      autologous blood in New Zealand rabbits. On the fourth day after subarachnoid
      haemorrhage, cerebral blood flow was monitored using transcranial Doppler
      ultrasonography during intracisternal and intracarotid saline and L-arginine
      infusions. RESULT: Cerebral blood flow measurements revealed resolution of
      vasospasm with short-term intracisternal and intracarotid L-arginine infusion. No
      significant difference was found between the effects of intracisternal and
      intracarotid L-arginine infusions, however intracarotid L-arginine infusion
      created a more potent vasodilatation towards the end of infusion. CONCLUSION:
      Both intracisternal and intracarotid short term L-arginine infusion significantly
      improve acute phase cerebral vasospasm after experimental subarachnoid
      haemorrhage. Intracarotid L-arginine infusion is more potent and safer as large
      amounts of intracisternal L-arginine may lead to overproduction of nitric oxide
      by inducible nitric oxide synthase with the production of free radicals.

PMID- 17430780
TI  - Intraspinal gas.
AB  - Intraspinal gas can be observed in a number of pathological settings including
      degenerative disc disease, infection, tumor or trauma, and in patients who have
      undergone therapeutic and diagnostic procedures. The air can be epidural,
      intradural or intradiscal. Intraspinal gas is usually asymptomatic. We report
      intraspinal gas in three patients, one with cervical, one with thoracic, and one
      with lumber disc disease and spondylolisthesis. The investigations were all
      completed at the the same medical center and CT and MRI were done in each case.
      The gas was in the epidural space in all three patients. These cases provide
      further evidence that intraspinal gas may persist without causing symptoms, and
      that resultant symptoms can disappear spontaneously. MRI is not reliable for
      diagnosing intraspinal gas; CT is recommended.

PMID- 17430781
TI  - Postpartum dissecting aneurysm of the posterior cerebral artery.
AB  - Intracranial dissecting aneurysm may cause subarachnoid hemorrhage (SAH) or
      infarction, and postpartum dissecting aneurysm is rare. A 30-year-old 6 days
      postpartum woman presented with posterior cerebral artery (PCA) dissection
      evolving dramatically over a short period. She had been well until 6 days after
      delivery when she suffered sudden onset of headache, vomiting, and
      unconsciousness. CT scan demonstrated SAH and digital subtraction angiography
      (DSA) revealed a fusiform dilatation of the left PCA (P3/P4 segment). The initial
      diagnosis was ruptured dissecting aneurysm, and conservative management was
      recommended in the acute period. DSA showed smoothening of the vascular wall 6
      days after onset, and obliteration of the left P3/P4 segment was observed 13 days
      after onset. She was discharged without neurological deficits 26 days after
      onset. Postpartum SAH due to dissecting aneurysm of the PCA is rare, but should
      be considered in the differential diagnosis of postpartum headache.

PMID- 17430782
TI  - Migration of lumbar disc herniation: an unusual case.
AB  - We illustrate a patient with a migrating lumbar disc fragment that caused a
      change in radicular symptoms from the L3 nerve root on one side to the L5 nerve
      root on the contralateral side, documented by magnetic resonance imaging (MRI).
      Our patient presented with 3 months of L3 pain on the right side with sensory and
      motor changes. Over a 24-hour time period, the right leg pain disappeared and he
      developed left leg pain attributable to left L5 nerve root compression.
      Investigation with MRI revealed an epidural mass, which was hypointense on Tl
      weighted and T2-weighted images that had migrated, initially compressing the
      right L3 nerve root, to now compress the left L5 nerve root. The patient did not
      wish to pursue surgery. Disc fragment migration patterns are discussed. We
      conclude that extruded disc fragments may migrate distant from their initial
      origin.

PMID- 17430783
TI  - Deep brain stimulation: a new treatment for hypertension?
AB  - We report a 61-year-old hypertensive man who underwent deep brain stimulation of
      the periventricular/periaqueductal grey area for the relief of chronic
      neuropathic pain affecting his oral cavity and soft palate. During intraoperative
      stimulation, we were able to modulate his blood pressure up or down, depending on
      electrode location. This is the first evidence that hypertension could be
      effectively treated with electrical stimulation of the midbrain.

PMID- 17430786
TI  - [On the way to understand the mechanism of immune tolerance].
AB  - This introductory paper deals with mechanisms playing important role in the
      development of immunological tolerance. Discusses the problems of "immunological
      self" and "non-self", the importance of the roles of AIRE gene products, as well
      as the role of dendritic cells and regulatory T-cells (T-reg cells) in immune
      tolerance and autoimmunity.

PMID- 17430787
TI  - [Pathogenetic features of autoimmune disorders].
AB  - Several disease susceptibility genes and environmental factors are implicated in
      the development of autoimmune diseases. Recent investigations help us to gain
      more and more deep insight into the pathomechanism of diseases with autoimmune
      pathomechanism. Rare monogenic diseases, caused by mutations of certain key
      susceptibility genes, animal models of autoimmune diseases as well as SNP- and
      microarray investigations contribute to our better understanding of autoimmune
      diseases. There are still numerous problematic questions related to autoimmunity.
      Current research in genomics might possibly provide us a basis for preventive
      medicine in the case of autoimmune diseases.

PMID- 17430788
TI  - [Does the number of patients with autoimmune disorders and the frequency of
      autoimmune diseases increase?].
AB  - Autoimmune diseases generally belong to the rare diseases, however, some of them
      are frequent in the population. In the present work the authors analyse whether
      can any increase be observed in the number of patients suffering from autoimmune
      diseases and whether do the frequency of certain autoimmune disorders increase.
      Due mainly to epigenetic factors the incidence of autoimmune diseases are
      increasing, therefore there are more patients recognised with particular
      disorders. On the other hand the incidence is increased by improving diagnostic
      possibilities, by the use of more specific and sensitive classification criteria
      and more sophisticated laboratory tests, resulted in the recognition of milder
      and atypical disease variants as well. The prevalence is also increasing in
      consequence of novel immune suppressive therapeutic possibilities and the
      consequent improvement of survival in the most of these diseases. Besides, more
      and more diseases have been revealed to have autoimmune background, and lot of
      new autoimmune syndromes, diseases have been characterised recently. This
      increases the number of the known autoimmune rheumatic disorders with a
      consequent increase in the number of autoimmune patients. Assigned to the
      increasing number of variable chronic autoimmune disorders, and the increasing
      number of disabled patients with such diseases increasing medical and social
      attention has to be focused on.

PMID- 17430789
TI  - [Types of autoimmune disorders. Classification].
AB  - In autoimmune diseases the immune system attacks self antigen(s). There are more
      then 80 autoimmune diseases occurring in 5-6% of the population. Autoimmune
      diseases can be classified as systemic or organ-specific, although the basic
      problem with this categorization is not based on causative pathogenic factors.
      The diseases are diagnosed based on safe international consensus criteria. Yet,
      by using these criteria we miss early forms of the diseases. We follow-up the
      course of the disease by histological and laboratory parameters, but we miss
      those biomarkers, which reflect the "disease of the immune system" itself. The
      number of autoimmune diseases is raising, more and more diseases turn out to have
      autoimmune pathogenesis in the background. The better understanding of the
      pathogenetic background helps to divide clinical and immunological phenotypes of
      the disease entities, which have important diagnostic and therapeutical
      consequences.

PMID- 17430790
TI  - [When does an autoimmune disease begin? Importance of the early diagnosis].
AB  - In autoimmune diseases, such as type I diabetes mellitus, systemic autoimmune
      diseases and the early phase of rheumatoid arthritis, before the development of a
      definitive disease, clinical and laboratory alterations can be observed. Being
      aware of these symptoms is crucial both for family practitioners and specialists,
      handling autoimmune and early arthritis patients. The early recognition and
      prognosticating of the disease and sending the patient immediately to a
      specialist will lead to the exponential improvement of the patient's life
      expectancies and will also help to avoid complications. The need for special
      diagnostics, care and treatment made the development of national immunological
      and rheumatological centers imperative, where sufficient experience and
      professional knowledge helps the proper medical attendance.

PMID- 17430791
TI  - [Hashimoto's thyroiditis, the model of organ-specific autoimmune disorders].
AB  - Anti-thyroid antibodies were published first in this disease. Research of past
      fifty years provided evidence that the damage of thyrocytes was the result of a
      multistep process in which immunological, immunogenetic, epigenetic and
      environmental factors had been involved. It was clarified that the autoimmune
      thyroiditis was not identical with hypothyroidism since during this disease
      different functional stages were differentiated. Both the clinical picture and
      the immunological investigations have been proved to be important in the
      diagnosis. The author summarized the main principles for treatment and prevention
      of this disorder.

PMID- 17430792
TI  - [Immune-mediated liver diseases].
AB  - The paper is devoted to overview the pathogenesis, diagnosis and treatment of the
      three immune-mediated liver diseases, autoimmune hepatitis, primary biliary
      cirrhosis and primary sclerosing cholangitis.

PMID- 17430793
TI  - [Antibody-mediated cell-specific hematopoietic autoimmune disorders].
AB  - Although it is clear that immunologic mechanisms play a significant role in the
      pathophysiology of many hematologic diseases, there are relative few situations
      where it is possible to gain a detailed understanding of immune damage in vivo in
      humans. Autoimmune hemolytic anemia, immune thrombocytopenia and immune
      neutropenia as antibody-mediated cell-specific disorders are of particular
      interest in this regard. Autoimmune hemolytic anemia represents a group of
      disorders in which individuals produce antibodies directed toward one or more of
      their own erythrocyte membrane antigens. This leads to destruction of the
      antibody-coated erythrocytes. The pathophysiology of the decreased erythrocyte
      survival has been examined with increasing sophistication for many years. This
      paper first discusses the underlying mechanisms responsible for autoimmune
      hemolytic anemias then consider immune thrombocytopenia and immune neutropenia.

PMID- 17430794
TI  - [Shared and distinctive characteristics of systemic autoimmune disorders].
AB  - Systemic autoimmune disorders constitute a well-characterized and separate group
      of diseases in the field of clinical immunology and rheumatology. Despite their
      shared characteristics, these diseases have several distinctive features. The
      similarity and the difference are manifested both in etiology (i.e. the
      importance and ratio of genetic and environmental factors), in pathomechanism
      (i.e. the dominance of cellular or humoral immune response), in the disease
      outcome (fluctuating or chronic progressive) and in the diversity of clinical
      manifestations (i.e. multiple organ involvements or some dominant target
      organs/tissues). In the present work the authors describe the features of four
      prototypic autoimmune disorders - systemic lupus erythematosus, Sjogren's
      disease, dermato-polymyositis and systemic sclerosis - and characterise in
      general the common and particular specific points of systemic autoimmune
      disorders focusing on the variability and subgroups which can be observed even
      within certain diseases.

PMID- 17430796
TI  - [New possibilities of treating patients with autoimmune disorders].
AB  - Autoimmune diseases vary in a wide range from mild to severe, intractable
      diseases. A great development of the therapy has been encountered in the past
      decades, in particular of formerly incapacitating diseases, such as rheumatoid
      arthritis or Crohn's disease. While biologic therapy, in particular monoclonal
      antibodies, offered most new solutions in these disorders, the therapy with many
      conventional drugs has also been rewritten. Old drugs, such as cyclophosphamide
      or intravenous immunoglobulin, retained their position in severe forms of
      autoimmunity. An evolving new area of stem cell transplantation offers benefit
      for the most severe patients suffering from intractable autoimmune diseases.

PMID- 17430795
TI  - [The autoimmune features of vasculopathies].
AB  - In the development of atherosclerotic plaques we can identify three autoantigens,
      the pathological value of which has been proven by experimental and clinical
      data. These antigens are the 60 kDa heat-shock-protein, beta2-glycoprotein I and
      oxidized LDL. They have role in the antigen-specific T-cell differentiation
      processes, moreover, against these antigens autoantibodies are produced, which
      have prothrombotic activity, leading to the acceleration of atherosclerosis. In
      autoimmune diseases besides these factors other mechanisms are present, which
      lead to the development of autoimmune vasculopathies. The current review gives an
      overview of these vasculopathies.

PMID- 17430797
TI  - [Biological therapy of arthritis and systemic autoimmune diseases].
AB  - The concept of biological therapy arises from the specific targeting of a factor,
      e.g. a cytokine, involved in the inflammatory cascade. Thus, biologicals disrupt
      the complex network of autoimmune-inflammatory events. Today, rheumatoid
      arthritis is a prototype disease in this context as most compounds have been
      tried in this disease. Recently, biological therapy has been introduced to the
      treatment of other diseases including various forms of arthritis, such as
      ankylosing spondylitis and psoriatic arthritis, as well as systemic autoimmune
      disorders, such as systemic lupus erythematosus, scleroderma, inflammatory
      myopathies and Sjogren's syndrome. Anti-tumor necrosis factor-alpha (TNF-alpha)
      agents play a central role in biological therapy as these agents have been
      successfully tried in most of these diseases. When seeking for specific targets
      for biologicals, pathogenic factors of the disease, such as Th1 or Th2 type
      responses, should be evaluated. Some mostly T-cell mediated diseases, such as
      rheumatoid arthritis, ankylosing spondylitis, psoriasis, polymyositis,
      polyarticular juvenile arthritis respond well to anti-TNF agents and T cell
      targeting, while others, such as lupus, Sjogren's syndrome, dermatomyositis may
      rather respond to anti-B cell biologicals. In this review, authors discuss the
      most recent advances in the biological therapy of arthritis and systemic
      autoimmune diseases including issues of efficacy and safety.

PMID- 17430798
TI  - [Plasmapheresis treatment in systemic autoimmune disorders].
AB  - It is necessary to rethink, from time to time, the efficacy of various treatment
      methods and, consequently, their place in the curing of certain pathological
      conditions. History of the development of methods throws a light on the fact that
      it is not always a question to be solved that brings about research; but there
      are cases when a technique realized for a totally different purpose is being used
      as a therapeutic process. In autoimmune illnesses, the plasmapheresis therapy is
      not of recent origin; in spite of that, however, a number of experiences,
      collected in the treatment of illnesses having divergent pathological symptoms,
      is not sufficient in itself to establish effectiveness without random double
      blind tests. Intervention trying to obtain results under any circumstances
      (heroic medicine) is to be avoided. When evaluating results in general, however,
      we must take into consideration the proportion of costs also (cost/benefit
      principle).

PMID- 17430799
TI  - [Patient care management in autoimmune disorders--the structure of treatment].

PMID- 17430800
TI  - A health profile of community-living nonagenarians in Canada.
AB  - Due to increasing life expectancy over time, persons who live into their ninety,
      known as nonagenarians, are an important and growing segment of the Canadian
      population. In 2001, there were 130,325 nonagenarians (compared to 3,795
      centenarians), and it is estimated that they will top 400,000 by 2026. This paper
      provides a health profile and an exploratory analysis of selected social
      determinants of health for community-living nonagenarians, using the 2001
      Canadian Community Health Survey (Statistics Canada, 2003). Perceived health,
      selection of prevalent chronic illnesses, and several health behaviours are
      examined. One dominant pattern is the tendency for male nonagenarians to be in
      better health than their female counterparts. This finding is consistent with
      research on centenarians and is discussed in terms of a mortality selection
      effect. Other key findings include the strength of sense of belonging, income,
      and physical activity as potential social determinants of health, connected to
      particular dimensions of health status.

PMID- 17430801
TI  - The potential of gait analysis to contribute to differential diagnosis of early
      stage dementia: current research and future directions.
AB  - Early differential diagnosis of dementia is becoming increasingly important as
      new pharmacologic therapies are developed, as these treatments are not equally
      effective for all types of dementia. Early detection and differential diagnosis
      also facilitates informed family decision making and timely access to appropriate
      services. Information about gait characteristics is informative in the diagnostic
      process and may have important implications for discriminating among dementia
      subtypes. The aim of this review paper is to summarize existing research
      examining the relationships between gait and dementia, including gait
      classification systems and assessment tools, gait patterns characteristic of
      different dementias (Alzheimer's disease, vascular dementia, dementia with Lewy
      Bodies, and fronto-temporal dementia), and the utility of gait analysis in early
      stage diagnosis. The paper concludes with implications for future research.

PMID- 17430802
TI  - Psychiatric illness in relation to frailty in community-dwelling elderly people
      without dementia: a report from the Canadian Study of Health and Aging.
AB  - We investigated whether frailty, defined as the accumulation of multiple,
      interacting illnesses, impairments and disabilities, is associated with
      psychiatric illness in older adults. Five-thousand-six-hundred-and-seventy-six
      community dwellers without dementia were identified within the Canadian Study of
      Health and Aging, and self-reported psychiatric illness was compared by levels of
      frailty (defined by an index of deficits that excluded mental illnesses). People
      with psychiatric illness (12.6% of those surveyed, who chiefly reported
      depression) had a higher mean frailty index value than those who did not. Older
      age was not associated with higher odds of psychiatric illness. Taking sex,
      frailty, and education into account, the odds of psychiatric illness decreased
      with each increasing year of age (OR 0.95; 95% CI, 0.94-0.97). Frailty was
      associated with psychiatric illness; for each additional deficit-defining
      frailty, odds of psychiatric illness increased (OR 1.23; 95% CI, 1.19-1.26).
      Similarly, psychiatric illness was associated with much higher odds of being
      among the most frail. These findings lend support to a multidimensional
      conceptualization of frailty. Our data also suggest that health care
      professionals who work with older adults with psychiatric illness should expect
      frailty to be common, and that those working with frail seniors should consider
      the possible co-existence of depression and psychiatric illness.

PMID- 17430803
TI  - The functional transitions model: maximizing ability in the context of
      progressive disability associated with Alzheimer's disease.
AB  - The Functional Transitions Model (FTM) integrates the theoretical notions of
      progressive functional decline associated with Alzheimer's disease (AD), excess
      disability, and transitions occurring intermittently along the trajectory of
      functional decline. Application of the Functional Transitions Model to clinical
      practice encompasses the paradox of attempting to minimize excess disability
      while anticipating the progressive functional decline associated with AD. It is
      suggested that times of functional transition are times of decision making and
      opportunities for interdisciplinary collaboration to identify and minimize excess
      disability, for revision of goals and expectations, and for provision of support
      to patients and caregivers. The model also is applicable as a conceptual
      framework for education and research.

PMID- 17430804
TI  - Standardized screening and assessment of older patients in the emergency
      department: a survey of implementation in Quebec.
AB  - Cost-effective methods have been developed to help busy emergency department (ED)
      staff cope with the growing number of older patients, including quick screening
      and assessment tools to identify those at high risk and note their specific
      needs. This survey, from a sample of key informants from all EDs (n = 111) in the
      province of Quebec (participation rate of 88.2%), investigated the implementation
      of these tools and barriers to implementation. Questionnaires (administered
      either by telephone or by self-completion) included characteristics of the ED,
      characteristics of the respondent, use of tools, and method of implementation.
      Barriers to the implementation of these tools included lack of resources for
      screening and follow-up, misunderstandings of the difference between screening
      and assessment tools, and need for adaptation of the tools to the local context.
      Education of staff and pre-implementation adaptation and testing are needed for
      successful implementation.

PMID- 17430805
TI  - [The tele-surveillance as a tool to favour social participation of elderly at
      home].
AB  - Little is known as yet about the impact of telesurveillance services on social
      participation. To document the interaction between telesurveillance services and
      social participation of the elderly living at home, a study was conducted in the
      context of a government call center employing nurses. A focus group study was
      realized with elders (n = 4), caregivers (n = 6), healthcare system practitioners
      and industry employees (n = 7). A qualitative analysis was performed using the
      Disability Creation Process model and generally accepted criteria for evaluating
      telehealth interventions. The results showed, on the one hand, factors that
      facilitate the use of telesurveillance services (user's intellectual
      capabilities, acceptance of clinical settings, relevance of recommendations, cost
      of service, and accessibility) and, on the other, factors that reinforce such use
      (user behaviors; level of satisfaction; impact on informal caregiver; system's
      level of performance; technical features; and life-habit aspects such as personal
      transportation, sleep, housekeeping, personal care, interpersonal relationships,
      and recreational activities).

PMID- 17430810
TI  - The study of charge transport through organic thin films: mechanism, tools and
      applications.
AB  - In this paper, we discuss the current state of organic and molecular-scale
      electronics, some experimental methods used to characterize charge transport
      through molecular junctions and some theoretical models (superexchange and
      barrier tunnelling models) used to explain experimental results. Junctions
      incorporating self-assembled monolayers of organic molecules - and, in
      particular, junctions with mercury-drop electrodes - are described in detail, as
      are the issues of irreproducibility associated with such junctions (due, in part,
      to defects at the metal-molecule interface).

PMID- 17430811
TI  - Self-assembled lamellar MoS2, SnS2 and SiO2 semiconducting polymer
      nanocomposites.
AB  - Lamellar nanocomposites based on semiconducting polymers incorporated into
      layered inorganic matrices are prepared by the co-assembly of organic and
      inorganic precursors. Semiconducting polymer-incorporated silica is prepared by
      introducing the semiconducting polymers into a tetrahydrofuran (THF)/water
      homogeneous sol solution containing silica precursor species and a surface-active
      agent. Semiconducting polymer-incorporated MoS(2) and SnS(2) are prepared by Li
      intercalation into the inorganic compound, exfoliation and restack in the
      presence of the semiconducting polymer. All lamellar nanocomposite films are
      organized in domains aligned parallel to the substrate surface plane. The
      incorporated polymers maintain their semiconducting properties, as evident from
      their optical absorption and photoluminescence spectra. The optoelectronic
      properties of the nanocomposites depend on the properties of both the inorganic
      host and the incorporated guest polymer as demonstrated by integrating the
      nanocomposite films into light-emitting diodes. Devices based on polymer
      incorporated silica and polymer-incorporated MoS(2) show no diode behaviour and
      no light emission due to the insulating and metallic properties of the silica and
      MoS(2) hosts. In contrast, diode performance and electroluminescence are obtained
      from devices based on semiconducting polymer-incorporated semiconducting SnS(2),
      demonstrating that judicious selection of the composite components in combination
      with the optimization of material synthesis conditions allows new hierarchical
      structures to be tailored for electronic and optoelectronic applications.

PMID- 17430812
TI  - Designing bistable [2]rotaxanes for molecular electronic devices.
AB  - The development of molecular electronic components has been accelerated by the
      promise of increased circuit densities and reduced power consumption. Bistable
      rotaxanes have been assembled into nanowire crossbar devices, where they may be
      switched between low- and high-conductivity states, forming the basis for a
      molecular memory. These memory devices have been scaled to densities of 10(11)
      bits cm(-2), the 2020 node for memory of the International Technology Roadmap for
      Semiconductors. Investigations of the kinetics and thermodynamics associated with
      the electromechanical switching processes of several bistable [2]rotaxane
      derivatives in solution, self-assembled monolayers on gold, polymer electrolyte
      gels and in molecular switch tunnel junction devices are consistent with a
      single, universal switching mechanism whose speed is dependent largely on the
      environment, as well as on the structure of the switching molecule. X-ray
      reflectometry studies of the bistable rotaxanes assembled into Langmuir
      monolayers also lend support to an oxidatively driven mechanical switching
      process. Structural information obtained from Fourier transform reflection
      absorption infrared spectroscopy of rotaxane monolayers taken before and after
      evaporation of a Ti top electrode confirmed that the functionality responsible
      for switching is not affected by the metal deposition process. All the
      considerable experimental data, taken together with detailed computational work,
      support the hypothesis that the tunnelling current hysteresis, which forms the
      basis of memory operation, is a direct result of the electromechanical switching
      of the bistable rotaxanes.

PMID- 17430813
TI  - Racial differences in the effects of age of onset on alcohol consumption and
      development of alcohol-related problems among males from mid-adolescence to young
      adulthood.
AB  - The purpose of this study was to explore the effects of race and sixth-grade
      alcohol use onset status (yes vs. no) on 8th grade intensity of alcohol use,
      number of post-high school drinking days, number of drinks per post-high school
      drinking day, and the development of lifetime alcohol-related problems in a
      sample of African American and White non-Hispanic males. MANOVA results indicated
      that African Americans had lower levels of alcohol use in both adolescence and
      young adulthood, and developed fewer alcohol-related problems. Furthermore, onset
      of alcohol use before sixth grade appeared to have a stronger effect among
      African Americans than among their White non-Hispanic peers on 8th grade
      intensity of alcohol use, the number of drinks consumed per drinking day in young
      adulthood, and the development of alcohol-related problems in young adulthood.

PMID- 17430814
TI  - Substance use among American Indian youth in an Eastern city.
AB  - This study represents one of the first efforts to examine substance use among
      American Indian (AI) youth in an Eastern city. As part of a school-based study in
      metropolitan Columbus, Ohio, 596 self-identified AI youth (grades 6-12) completed
      surveys describing their use of alcohol, cigarettes, smokeless tobacco, marijuana
      and inhalants. Net of gender, grade and family structure, AI youth were more
      likely than their white peers to regularly use most substances while overall
      prevalence resembled estimates from studies of urban AI youth in the Western
      United States. These findings highlight the complex interactions of geography,
      identity and risk behavior among ethnic minority adolescents.

PMID- 17430815
TI  - Space Scouts: a collaboration between university researchers and African American
      churches.
AB  - Space Scouts, funded by the National Institute on Drug Abuse (NIDA) and produced
      by the Missouri Institute of Mental Health (MIMH), is a three-episode series of
      media tools designed to teach fourth-, fifth-, and sixth-grade children from
      African American churches about the science of drug addiction. This article
      examines the effectiveness of the principles of practice for community-based
      participatory research used to create Space Scouts. Academic researchers at MIMH
      collaborated with an inter-faith agency-Committed Caring Faith Communities (CCFC)
      and solicited feedback from members of the target audience, their pastors, and
      other church staff, substance abuse researchers, and curriculum development
      specialists in order to ensure that the final program would meet the needs of all
      involved parties.

PMID- 17430816
TI  - Substance use among a sample of foreign- and U.S.-born southeast Asians in an
      urban setting.
AB  - Asian Americans (AA) are thought to have the lowest rates of substance use. This
      study examined substance use prevalence among 494 urban-dwelling Southeast Asians
      using snowball techniques. Prevalence estimates were age-adjusted proportionate
      to the U.S. Asian population. Findings show beer and alcohol consumption
      approximated the national percentage among 25-44 year olds. U.S.-born were about
      three times likelier to have past month substance use. Foreign-born Vietnamese
      were likelier than U.S.-born to use all substances except for beer. U.S.- and
      foreign-born beer consumption rates were similar. Future research is needed to
      delineate substance use determinants and patterns in foreign and U.S.-born AA sub
      groups.

PMID- 17430817
TI  - African American parents' behaviors and attitudes about substance use and abuse.
AB  - Limited information exists about African American parents' substance use and
      attitudes, independent of how they relate to their children. This study examined
      whether the behaviors and attitudes of a sample of African American parents
      differed from the general population of adults. Results indicated their attitudes
      were relatively more conservative, and that alcohol and illicit drug use were
      lower. Cigarette and marijuana use were comparable. Correlations between
      attitudes and behaviors were found. Findings suggest that increased educational
      efforts are needed among parents, especially about cigarettes, marijuana, and the
      negative impact these attitudes and behaviors may have on their children.

PMID- 17430818
TI  - Change in the scenery: an ethnographic exploration of crack cocaine use in rural
      Ohio.
AB  - Though still largely perceived as an "inner city" drug, crack cocaine has become
      increasingly available in many areas of the United States. However, little
      research has been conducted on the phenomenon of crack cocaine use outside of
      urban areas. This paper draws on qualitative interviews with 50 recent and former
      crack-cocaine users to explore patterns of use and distribution in three counties
      in rural Ohio. The findings show that variable patterns of crack use previously
      documented among urban crack users are evident in rural areas as well, though
      these are modified by the context of the rural small town. It is postulated that
      local social networks are the primary means by which these patterns are both
      transmitted and translated. Implications of these exploratory findings and
      possible directions for future research are discussed.

PMID- 17430819
TI  - It's all about "connecting": reasons for drug use among Latino gay men living in
      the San Francisco Bay Area.
AB  - Research on Latino gay men drug use is limited. This study explores the
      narratives of 16 Latino drug-using gay men living in the San Francisco Bay Area
      by exploring the role social settings play in their drug use, as well as by
      identifying the reasons and motivations for drug-use. Using a thematic content
      analysis, 16 interviews with LGM living in the San Francisco Bay Area were
      analyzed. Results suggest LGMhave different reasons for drug use across multiple
      settings. Participants use drugs to cope with their sexual identity, to feel like
      part of the mainstream gay community, and to reduce sexual inhibitions.
      Understanding how Latino gay men (LGM) perceive their drug use within their
      social, political, and economic environment would aid in the development of
      culturally adequate interventions.

PMID- 17430820
TI  - Former Soviet Union immigrant and native-born adolescents in Israel: substance
      use and related problem behavior.
AB  - Studies on immigration and adolescence show that youth experience a variety of
      emotional and cognitive adjustments as well as conflicts related to acculturation
      and the realities of life in their new country. Such conditions place many of
      them at increased risk for psychosocial problems including personal stress,
      interpersonal conflicts, mental illness, school failure, delinquency, substance
      use, and other risk-taking behavior. This prospective study compares the patterns
      of substance use and problem behaviors among 365 at-risk adolescents born in
      Israel and those who immigrated to that country from the Former Soviet Union.
      Findings show that Former Soviet Union youth tend to have higher levels of last
      30-day alcohol and ecstasy use and binge drinking. Multiple regression shows
      binge drinking behavior related to trading property to obtain drugs;
      deterioration of school achievement; selling drugs; and time spent when being
      absent from school and hanging around during the day. Country of origin was not
      found related to this behavior. Further research is needed to study substance use
      and related problem behavior among immigrant youth controlling for the impact of
      acculturation and other factors.

PMID- 17430822
TI  - Addressing the growing discordance between clinicians and regulators.

PMID- 17430823
TI  - The Declarations of Venice of 1983 and 2006: two efforts to improve palliative
      care.

PMID- 17430824
TI  - Chronic administration of ketamine for analgesia.
AB  - Use of the dissociative anesthetic ketamine in subanesthetic doses has
      demonstrated efficacy in neuropathic pain. This article reviews the scientific
      and clinical literature on ketamine. Mechanisms of both central and peripheral
      neuropathic pain are described. Studies of ketamine analgesia in postherpetic
      neuralgia, phantom pain, complex regional pain syndrome and cancer pain are
      reviewed. A range of administration methods for ketamine including neuroaxial
      administration are described.

PMID- 17430825
TI  - Adverse effects of opioids on the central nervous systems of palliative care
      patients.
AB  - Opioids, defined as drugs that stimulate opioid receptors, are primarily used in
      the treatment of moderate to severe pain. They induce central nervous system
      (CNS) adverse effects which can be divided into three groups. The first group
      includes effects that lower the level of consciousness-sedation, drowsiness and
      sleep disturbance. The second group affects the thinking process and the ability
      to react-cognitive impairment, psychomotor impairment, delirium, hallucinations,
      dreams and nightmares. The third group is of the direct toxic effects of opioids
      on neurons and includes myoclonus (perhaps), hyperalgesia and tolerance. This
      review addresses the incidence, possible mechanisms, and treatment of each of
      these groups of opioid-induced adverse effects.

PMID- 17430826
TI  - Pain relieving effect of short-course, pulse prednisolone in managing frozen
      shoulder.
AB  - Adhesive capsulitis or frozen shoulder is a common condition characterized by
      shoulder pain and stiffness in which conservative methods of treatment such as
      glucocorticosteroids, anti-inflammatory drugs, and physiotherapy play a
      significant part. To evaluate the pain relieving effect of short-course pulse
      prednisolone, this comparison study was planed. Two age and sex-matched groups of
      patients were studied during three years. Each group consisted of thirty patients
      suffered from idiopathic Frozen Shoulder. The mean duration from the onset of the
      disorder to referral to our clinic was five months. Patients' pain on external
      rotation was qualified using a visual analog scale before and after finishing the
      treatment. The first group received oral diclofenac (100 mg/day) and
      physiotherapy. The second group received 500 mg of prednisolone intravenously
      (i.v.) for three consecutive days at the beginning of treatment in addition to
      the full treatment regimen of the first group. The pain relieving effects of the
      two methods of treatment were compared. The mean pain scale for the first group
      decreased from 7.16 to 4.9 (p < 0.001) and for the second group from 7.10 to 2.96
      (p < 0.001) as indicated by Paired sample test. Based on the results of this
      study, inclusion of 500 mg prednisolone for three days appears to improve the
      pain-relieving effect of routine conservative treatment of frozen shoulder using
      NSAIDs and physiotherapy.

PMID- 17430827
TI  - The Declaration of Venice: palliative care research in developing countries.
AB  - In May 2006 at the Fourth Research Forum of the European Association for
      Palliative Care (EAPC) in Venice Italy, recognizing that the World Health
      Organization definition of palliative care calls for "impeccable assessment and
      treatment of physical symptoms and of psychological, social and spiritual
      problems," the EAPC and the International Association for Hospice and Palliative
      Care (IAPC) introduced a declaration to develop a global palliative care research
      initiative.

PMID- 17430828
TI  - In my opinion... opioid tolerance.
AB  - A commentary on the problem of tolerance to opioids is presented from the
      perspective of a person with chronic nonmalignant pain. The writer challenges the
      position of many clinicians and professional societies that tolerance to opioid
      analgesia usually is not a barrier to effective pain management. Implications for
      clinicians are presented.

PMID- 17430829
TI  - Will the number of milligrams of an opioid dose ever re-achieve the truly
      meaningless status it deserves?
AB  - There is a notion that tolerance is an inevitable complication when patients are
      maintained on opioid analgesic regimens for an extended period of time. Whether
      this is true or not, it is important to remember that, in spite of growing
      regulatory scrutiny and spreading fear around these medications, defining
      "ceiling doses" of opioids has more to do with clinician comfort and much less to
      do with reality and patient requirements. This commentary posits that clinicians
      must return to the principles of balancing efficacy with toxicity as the dose
      limiting factor once again, contextualized by outcomes in the areas of function
      and compliant drug-taking.

PMID- 17430830
TI  - A chronic pain patient's perspective on opioid tolerance.
AB  - A response to the preceding commentary is provided form the perspective of a
      bioethicist.

PMID- 17430831
TI  - Debunking myths of negligence in pain management practice.
AB  - Pain management practitioners must meet the standard of care to avoid liability
      for malpractice. The Court of Appeals of Florida has recently reversed a jury
      verdict against a surgeon who provided pain management care to a patient who died
      after overdosing on opioids obtained from a different physician. The plaintiffs
      had contended that the surgeon breached the standard of care by failing to
      perform specific activities that would have prevented the patient from obtaining
      the drugs that cause her death. The appellate court rejected the plaintiffs'
      argument because the evidence failed to support malpractice liability of the
      surgeon.

PMID- 17430832
TI  - Evidence-based pain management and palliative care in issue three for 2006 of The
      Cochrane Library.
AB  - The Cochrane Library of Systematic Reviews is published quarterly. It now
      contains 2785 complete reviews, 1625 protocols of reviews and 5574 one page
      summaries of systematic reviews published in the general medical literature. In
      addition there are citations of 477,942 randomized controlled trials, 23
      methodology reviews and 8408 cited papers in the Cochrane methodology register.
      The health technology assessment database contains 6011 citations. This edition
      of the Library contains 111 new reviews of which 9 have potential relevance for
      practitioners in pain and palliative medicine.

PMID- 17430833
TI  - White Paper on opioid usage improves legislation in Austria.
AB  - The White Paper on Opioids and Pain: A Pan-European Challenge, which was
      presented to the European Parliament, has led to legislation in Austria to
      improve opioid usage. Process and outcomes of this work are summarized.

PMID- 17430834
TI  - Neurological effects of chronic pain.
AB  - Studies of neurobiological changes that occur in patients with chronic pain are
      described. These include grey matter loss, effects on emotional processing and
      learning.

PMID- 17430835
TI  - Respiratory depression with opioids.
AB  - Respiratory depression remains one of the most feared effects of opioids.
      Guidelines for safe use of these important drugs are presented and clinicians are
      encouraged to not fear using opioids when they are clinically indicated.

PMID- 17430838
TI  - Pregabalin and duloxetine for the treatment of neuropathic pain disorders.
AB  - Clinical studies investigating the use of pregabalin and duloxetine for the
      management of diabetic peripheral neuropathy and post-herpetic neuralgia are
      reviewed. The benefits and potential drawbacks associated with these agents are
      discussed.

PMID- 17430845
TI  - Oral or inhaled corticosteroids for the treatment of croup?

PMID- 17430844
TI  - Post-traumatic stress disorder in childhood.

PMID- 17430846
TI  - Management of postoperative pain in children.

PMID- 17430847
TI  - Management of procedural pain in children.

PMID- 17430848
TI  - Tuberculosis: diagnosis, management and prevention.

PMID- 17430849
TI  - A rotavirus vaccine for infants prevented rotavirus gastroenteritis with no
      increase in risk of intussusception.

PMID- 17430850
TI  - Budesonide-formoterol for maintenance and as needed reliever treatment reduced
      asthma exacerbations.

PMID- 17430851
TI  - Review: tissue transglutaminase test is almost as accurate as endomysial antibody
      test for diagnosis of coeliac disease.

PMID- 17430852
TI  - Not so funny turns.

PMID- 17430853
TI  - Respiratory failure in a newborn infant.

PMID- 17430854
TI  - When does a knee "need" a "joint" assessment?

PMID- 17430855
TI  - Medicines for migraine.

PMID- 17430856
TI  - Atopic dermatitis and food allergies: true, true and related?

PMID- 17430857
TI  - Routine postnatal care given to all babies.

PMID- 17430858
TI  - Management of chronic non-specific cough in childhood: an evidence-based review.

PMID- 17430859
TI  - Ageing and Parkinson's disease.

PMID- 17430860
TI  - Parasomnias: the spectrum of things that go bump in the night.

PMID- 17430861
TI  - Progressive supranuclear palsy.

PMID- 17430862
TI  - Walking sticks and frames for patients with neurological disorders.

PMID- 17430863
TI  - Are antibasal ganglia antibodies important, and clinically useful?

PMID- 17430864
TI  - Memory dysfunction in neurological practice.

PMID- 17430865
TI  - Eosinophilic myelitis, a souvenir from South East Asia.

PMID- 17430868
TI  - Ireland.

PMID- 17430866
TI  - Stroke due to a cardiac myxoma.

PMID- 17430869
TI  - Diagnostic DNA testing and consent.

PMID- 17430870
TI  - No ghosts here please.

PMID- 17430871
TI  - ALS: pitfalls in the diagnosis.

PMID- 17430872
TI  - Diabetic neuropathies.

PMID- 17430873
TI  - Sorting out the inherited neuropathies.

PMID- 17430874
TI  - Stiff-person syndrome.

PMID- 17430875
TI  - "Ice-on-eyes", a simple test for myasthenia gravis presenting with ocular
      symptoms.

PMID- 17430876
TI  - Refractory neurosarcoidosis responsive to infliximab.

PMID- 17430877
TI  - Preventing neurophobia in medical students, and so future doctors.

PMID- 17430878
TI  - The stranger within.

PMID- 17430879
TI  - Iceland.

PMID- 17430880
TI  - How good at neurology are you? Behcet's syndrome.

PMID- 17430881
TI  - Parkinson's disease: trials and travesties.

PMID- 17430882
TI  - Acid-sensing ion channels in sensory perception.

PMID- 17430883
TI  - Evidence for a pro-oxidant intermediate in the assembly of cytochrome oxidase.
AB  - The hydrogen peroxide sensitivity of cells lacking two proteins, Sco1 and Cox11,
      important in the assembly of cytochrome c oxidase (CcO), is shown to arise from
      the transient accumulation of a pro-oxidant heme A-Cox1 stalled intermediate. The
      peroxide sensitivity of these cells is abrogated by a reduction in either Cox1
      expression or heme A formation but exacerbated by either enhanced Cox1 expression
      or heme A production arising from overexpression of COX15. Sco1 and Cox11 are
      implicated in the formation of the Cu(A) and Cu(B) sites of CcO, respectively.
      The respective wild-type genes suppress the peroxide sensitivities of sco1Delta
      and cox11Delta cells, but no cross-complementation is seen with noncognate genes.
      Copper-binding mutant alleles of Sco1 and Cox11 that are nonfunctional in
      promoting the assembly of CcO are functional in suppressing the peroxide
      sensitivity of their respective null mutants. Likewise, human Sco1 that is
      nonfunctional in yeast CcO assembly is able to suppress the peroxide sensitivity
      of yeast sco1Delta cells. Thus, a disconnect exists between the respiratory
      capacity of cells and hydrogen peroxide sensitivity. Hydrogen peroxide
      sensitivity of sco1Delta and cox11Delta cells is abrogated by overexpression of a
      novel mitochondrial ATPase Afg1 that promotes the degradation of CcO
      mitochondrially encoded subunits. Studies on the hydrogen peroxide sensitivity in
      CcO assembly mutants reveal new aspects of the CcO assembly process.

PMID- 17430884
TI  - Proteolytic activities of human ADAMTS-5: comparative studies with ADAMTS-4.
AB  - Aggrecanases have been characterized as proteinases that cleave the Glu373-Ala374
      bond of the aggrecan core protein, and they are multidomain metalloproteinases
      belonging to the ADAMTS (adamalysin with thrombospondin type 1 motifs) family.
      The first aggrecanases discovered were ADAMTS-4 (aggrecanase 1) and ADAMTS-5
      (aggrecanase 2). They contain a zinc catalytic domain followed by non-catalytic
      ancillary domains, including a disintegrin domain, a thrombospondin domain, a
      cysteine-rich domain, and a spacer domain. In the case of ADAMTS-5, a second
      thrombospondin domain follows the spacer domain. We previously reported that the
      non-catalytic domains of ADAMTS-4 influence both its extracellular matrix
      interaction and proteolytic abilities. Here we report the effects of these
      domains of ADAMTS-5 on the extracellular matrix interaction and proteolytic
      activities and compare them with those of ADAMTS-4. Although the spacer domain
      was critical for ADAMTS-4 localization in the matrix, the cysteine-rich domain
      influenced ADAMTS-5 localization. Similar to previous reports of other ADAMTS
      family members, very little proteolytic activity was detected with the ADAMTS-5
      catalytic domain alone. The sequential inclusion of each carboxyl-terminal domain
      enhanced its activity against aggrecan, carboxymethylated transferrin,
      fibromodulin, decorin, biglycan, and fibronectin. Both ADAMTS-4 and -5 had a
      broad optimal activity at pH 7.0-9.5. Aggrecanolytic activities were sensitive to
      the NaCl concentration, but activities on non-aggrecan substrates, e.g.
      carboxymethylated transferrin, were not affected. Although ADAMTS-4 and ADAMTS-5
      had similar general proteolytic activities, the aggrecanase activity of ADAMTS-5
      was at least 1,000-fold greater than that of ADAMTS-4 under physiological
      conditions. Our studies suggest that ADAMTS-5 is a major aggrecanase in cartilage
      metabolism and pathology.

PMID- 17430885
TI  - ATP-sensitive potassium channel in mitochondria of the eukaryotic microorganism
      Acanthamoeba castellanii.
AB  - We describe the existence of a potassium ion transport mechanism in the
      mitochondrial inner membrane of a lower eukaryotic organism, Acanthamoeba
      castellanii. We found that substances known to modulate potassium channel
      activity influenced the bioenergetics of A. castellanii mitochondria. In isolated
      mitochondria, the rate of resting respiration is increased by about 10% in
      response to potassium channel openers, i.e. diazoxide and BMS-191095, during
      succinate-, malate-, or NADH-sustained respiration. This effect is strictly
      dependent on the presence of potassium ions in an incubation medium and is
      reversed by glibenclamide (a potassium channel blocker). Diazoxide and BMS-191095
      also caused a slight but statistically significant depolarization of
      mitochondrial membrane potential (measured with a TPP(+)-specific electrode),
      regardless of the respiratory substrate used. The resulting steady state value of
      membrane potential was restored after treatment with glibenclamide or 1 mM ATP.
      Additionally, the electrophysiological properties of potassium channels present
      in the A. castellanii inner mitochondrial membrane are described in the
      reconstituted system, using black lipid membranes. Conductance from 90 +/- 7 to
      166 +/- 10 picosiemens, inhibition by 1 mM ATP/Mg(2+) or glibenclamide, and
      activation by diazoxide were observed. These results suggest that an ATP
      sensitive potassium channel similar to that of mammalian mitochondria is present
      in A. castellanii mitochondria.

PMID- 17430886
TI  - Activation of poly(ADP)-ribose polymerase (PARP-1) induces release of the pro
      inflammatory mediator HMGB1 from the nucleus.
AB  - Necrotic cells release inflammatory mediators that activate cytokine production
      from innate immune cells. One mediator of this activation is high mobility group
      box 1 protein (HMGB1). HMGB1 is normally a chromatin-associated protein and is
      sequestered at condensed chromatin during apoptosis. How it is released from
      chromatin during necrotic cell death is not known. Here we show that after DNA
      alkylating damage, the activation of poly(ADP)-ribose polymerase (PARP) regulates
      the translocation of HMGB1 from the nucleus to the cytosol. This displaced HMGB1
      is subject to release if the cell then loses plasma membrane integrity as a
      result of necrosis. Both full-length HMGB1 and a truncated form of HMGB1 lacking
      the highly conserved glutamate-rich C-terminal tail can induce macrophage
      activation and tumor necrosis factor-alpha production. However, displacement of
      HMGB1 from the nucleus following PARP activation requires the presence of the
      glutamate-rich C-terminal tail. Although the C-terminal tail is not the sole
      substrate for PARP modification of HMGB1, it appears to be required to
      destabilize HMGB1 association with chromatin following PARP-dependent chromatin
      modifications. These data suggest that PARP-dependent nuclear-to-cytosolic
      translocation of HMGB1 serves to establish the ability of cells to release this
      potent inflammatory mediator upon subsequent necrotic death.

PMID- 17430887
TI  - Binding of phosphoinositide-specific phospholipase C-zeta (PLC-zeta) to
      phospholipid membranes: potential role of an unstructured cluster of basic
      residues.
AB  - Phospholipase C-zeta (PLC-zeta) is a sperm-specific enzyme that initiates the
      Ca2+ oscillations in mammalian eggs that activate embryo development. It shares
      considerable sequence homology with PLC-delta1, but lacks the PH domain that
      anchors PLC-delta1 to phosphatidylinositol 4,5-bisphosphate, PIP2. Thus it is
      unclear how PLC-zeta interacts with membranes. The linker region between the X
      and Y catalytic domains of PLC-zeta, however, contains a cluster of basic
      residues not present in PLC-delta1. Application of electrostatic theory to a
      homology model of PLC-zeta suggests this basic cluster could interact with acidic
      lipids. We measured the binding of catalytically competent mouse PLC-zeta to
      phospholipid vesicles: for 2:1 phosphatidylcholine/phosphatidylserine (PC/PS)
      vesicles, the molar partition coefficient, K, is too weak to be of physiological
      significance. Incorporating 1% PIP2 into the 2:1 PC/PS vesicles increases K about
      10-fold, to 5x10(3) M-1, a biologically relevant value. Expressed fragments
      corresponding to the PLC-zeta X-Y linker region also bind with higher affinity to
      polyvalent than monovalent phosphoinositides on nitrocellulose filters. A peptide
      corresponding to the basic cluster (charge=+7) within the linker region, PLC-zeta
      (374-385), binds to PC/PS vesicles with higher affinity than PLC-zeta, but its
      binding is less sensitive to incorporating PIP2. The acidic residues flanking
      this basic cluster in PLC-zeta may account for both these phenomena. FRET
      experiments suggest the basic cluster could not only anchor the protein to the
      membrane, but also enhance the local concentration of PIP2 adjacent to the
      catalytic domain.

PMID- 17430888
TI  - H2S, endoplasmic reticulum stress, and apoptosis of insulin-secreting beta cells.
AB  - Cystathionine gamma-lyase (CSE) is a key enzyme in the trans-sulfuration pathway,
      which uses L-cysteine to produce hydrogen sulfide (H2S). Functional changes of
      pancreatic beta cells induced by endogenous H2S have been reported, but the
      effect of the CSE/H2S system on pancreatic beta cell survival has not been known.
      In this study, we demonstrate that H2Sat physiologically relevant concentrations
      induced apoptosis of INS-1E cells, an insulin-secreting beta cell line.
      Transfection of INS-1E cells with a recombinant defective adenovirus containing
      the CSE gene (Ad-CSE) resulted in a significant increase in CSE expression and
      H2S production. Ad-CSE transfection also stimulated apoptosis. The other two end
      products of CSE-catalyzed enzymatic reaction, ammonium and pyruvate, had no
      effects on INS-1E cell apoptosis, indicating that overexpression of CSE may
      stimulate INS-1E cell apoptosis via increased endogenous production of H2S. Both
      exogenous H2S (100 microM) and Ad-CSE transfection inhibited ERK1/2 but activated
      p38 MAPK. Interestingly, BiP and CHOP, two indicators of endoplasmic reticulum
      (ER) stress, were up-regulated in H2S-and CSE-mediated apoptosis in INS-1E cells.
      After suppressing CHOP mRNA expression, H2S-induced apoptosis of INS-1E cells was
      significantly decreased. Inhibition of p38 MAPK, but not of ERK1/2, inhibited the
      expression of BiP and CHOP and decreased H2S-stimulated apoptosis, suggesting
      that p38 MAPK activation functions upstream of ER stress to initiate H2S-induced
      apoptosis. It is concluded that H2S induces apoptosis of insulin-secreting beta
      cells by enhancing ER stress via p38 MAPK activation. Our findings may help
      unmask a novel role of CSE/H2S system in regulating pancreatic functions under
      physiological condition and in diabetes.

PMID- 17430889
TI  - Human OLA1 defines an ATPase subfamily in the Obg family of GTP-binding proteins.
AB  - Purine nucleotide-binding proteins build the large family of P-loop GTPases and
      related ATPases, which perform essential functions in all kingdoms of life. The
      Obg family comprises a group of ancient GTPases belonging to the TRAFAC (for
      translation factors) class and can be subdivided into several distinct protein
      subfamilies. The founding member of one of these subfamilies is the bacterial P
      loop NTPase YchF, which had so far been assumed to act as GTPase. We have
      biochemically characterized the human homologue of YchF and found that it binds
      and hydrolyzes ATP more efficiently than GTP. For this reason, we have termed the
      protein hOLA1, for human Obg-like ATPase 1. Further biochemical characterization
      of YchF proteins from different species revealed that ATPase activity is a
      general but previously missed feature of the YchF subfamily of Obg-like GTPases.
      To explain ATP specificity of hOLA1, we have solved the x-ray structure of hOLA1
      bound to the nonhydrolyzable ATP analogue AMPPCP. Our structural data help to
      explain the altered nucleotide specificity of YchF homologues and identify the
      Ola1/YchF subfamily of the Obg-related NTPases as an exceptional example of a
      single protein subfamily, which has evolved altered nucleotide specificity within
      a distinct protein family of GTPases.

PMID- 17430890
TI  - Identification of novel Wilms' tumor suppressor gene target genes implicated in
      kidney development.
AB  - The Wilms' tumor suppressor gene (WT1) encodes a zinc finger transcription factor
      that is vital during development of several organs including metanephric kidneys.
      Despite the critical regulatory role of WT1, the pathways and mechanisms by which
      WT1 orchestrates development remain elusive. To identify WT1 target genes, we
      performed a genome-wide expression profiling analysis in cells expressing
      inducible WT1. We identified a number of direct WT1 target genes, including the
      epidermal growth factor (EGF)-family ligands epiregulin and HB-EGF, the chemokine
      CX3CL1, and the transcription factors SLUG and JUNB. The target genes were
      validated using quantitative reverse transcriptase-polymerase chain reaction,
      small interfering RNA knockdowns, chromatin immunoprecipitation, and luciferase
      reporter analyses. Immunohistochemistry of fetal kidneys confirmed that a number
      of the WT1 target genes had overlapping expression patterns with the highly
      restricted spatiotemporal expression of WT1. Finally, using an in vitro embryonic
      kidney culture assay, we found that the addition of recombinant epiregulin,
      amphiregulin, CX3CL1, and interleukin-11 significantly enhanced ureteric bud
      branching morphogenesis. Our genome-wide screen implicates WT1 in the
      transcriptional regulation of the EGF-family of growth factors as well as the
      CX3CL1 chemokine during nephrogenesis.

PMID- 17430891
TI  - Transcriptional activators and repressors for the neuron-specific expression of a
      metabotropic glutamate receptor.
AB  - Metabotropic glutamate receptor 1 (mGlu1) has a discrete distribution in the
      central nervous system restricted to neurons. Its expression undergoes important
      changes during development and in response to physiological and pathological
      modifications. Here, we have determined the structure of the mGlu1 gene and
      demonstrated that mGlu1 transcription takes places at alternative first exons.
      Moreover, we have identified active promoter regions upstream from the two most
      expressed first exons by means of luciferase reporter gene assays performed in
      primary cerebellar granule neurons. Targeted mutations of active elements
      constituting the core promoter and electrophoretic mobility shift assays
      demonstrated that the factors thyroid transcription factor-1 and CCAAT/enhancer
      binding proteins beta act synergistically to promote mGlu1 transcription. We have
      also elucidated the molecular bases for the neuron-specific expression of mGlu1
      identifying a neural restrictive silencing element and a regulatory factor for X
      box element, which suppressed mGlu1 expression in nonneuronal cells. These
      results reveal the molecular bases for cell- and context-specific expression of
      an important glutamate receptor critically involved in synaptogenesis, neuronal
      differentiation, synaptic transmission, and plasticity.

PMID- 17430892
TI  - Caspase inhibition sensitizes inhibitor of NF-kappaB kinase beta-deficient
      fibroblasts to caspase-independent cell death via the generation of reactive
      oxygen species.
AB  - Cells lacking functional NF-kappaB die after ligation of some tumor necrosis
      factor (TNF) receptor family members through failure to express NF-kappaB
      dependent anti-apoptotic genes. NF-kappaB activation requires the IkappaB kinase
      (IKK) complex containing two catalytic subunits named IKKalpha and IKKbeta that
      regulate distinct NF-kappaB pathways. IKKbeta is critical for classical signaling
      that induces pro-inflammatory and anti-apoptotic gene profiles, whereas IKKalpha
      regulates the non-canonical pathway involved in lymphoid organogenesis and B-cell
      development. To determine whether IKKalpha and IKKbeta differentially function in
      rescuing cells from death induced by activators of the classical and non
      canonical pathways, we analyzed death after ligation of the TNF and lymphotoxin
      beta receptors, respectively. Using murine embryonic fibroblasts (MEFs) lacking
      each of the IKKs, the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp
      fluoromethyl ketone, and dominant negative Fas-associated death domain protein,
      we found that deletion of these kinases sensitized MEFs to distinct cell death
      pathways. MEFs lacking IKKalpha were sensitized to death in response to both
      cytokines that was entirely caspase-dependent, demonstrating that IKKalpha
      functions in this process. Surprisingly, death of IKKbeta-/- MEFs was not blocked
      by caspase inhibition, demonstrating that IKKbeta negatively regulates caspase
      independent cell death (CICD). CICD was strongly activated by both TNF and
      lymphotoxin-beta receptor ligation in IKKbeta-/- MEFs and was accompanied by loss
      of mitochondrial membrane potential and the generation of reactive oxygen
      species. CICD was inhibited by the anti-oxidant butylated hydroxyanosole and
      overexpression of Bcl-2, neither of which blocked caspase-dependent apoptosis.
      Our findings, therefore, demonstrate that both IKKalpha and IKKbeta regulate
      cytokine-induced apoptosis, and IKKbeta additionally represses reactive oxygen
      species- and mitochondrial-dependent CICD.

PMID- 17430893
TI  - HoxA10 activates transcription of the gene encoding mitogen-activated protein
      kinase phosphatase 2 (Mkp2) in myeloid cells.
AB  - HoxA10 is a homeodomain transcription factor that is frequently overexpressed in
      human acute myeloid leukemia. In murine bone marrow transplantation studies,
      HoxA10 overexpression induces a myeloproliferative disorder with accumulation of
      mature phagocytes in the peripheral blood and tissues. Over time, differentiation
      block develops in these animals, resulting in acute myeloid leukemia. In immature
      myeloid cells, HoxA10 represses transcription of some genes that confer the
      mature phagocyte phenotype. Therefore, overexpressed HoxA10 blocks
      differentiation by repressing myeloid-specific gene transcription in
      differentiating myeloid cells. In contrast, target genes involved in
      myeloproliferation due to HoxA10 overexpression have not been identified. To
      identify such genes, we screened a CpG island microarray with HoxA10 co
      immunoprecipitating chromatin. We identified the DUSP4 gene, which encodes
      mitogen-activated protein kinase phosphatase 2 (Mkp2), as a HoxA10 target gene.
      We analyzed the DUSP4 5'-flank and identified two proximal-promoter cis elements
      that are activated by HoxA10. We find that DUSP4 transcription and Mkp2
      expression decrease during normal myelopoiesis. However, this down-regulation is
      impaired in myeloid cells overexpressing HoxA10. In hematopoietic cells, c-Jun N
      terminal kinases (Jnk) are the preferred substrates for Mkp2. Therefore, Mkp2
      inhibits apoptosis by dephosphorylating (inactivating) Jnk. Consistent with this,
      HoxA10 overexpression decreases apoptosis in differentiating myeloid cells.
      Therefore, our studies identify a mechanism by which overexpressed HoxA10
      contributes to inappropriate cell survival during myelopoiesis.

PMID- 17430894
TI  - Role of the transcription factor ATF4 in the anabolic actions of insulin and the
      anti-anabolic actions of glucocorticoids.
AB  - In most mammalian cells, insulin and glucocorticoids promote anabolism and
      catabolism, respectively. Whereas the opposing effects of insulin and
      glucocorticoids on catabolic gene expression have been explained at the molecular
      level, comparatively little is known about how these hormones alter anabolic gene
      expression. These studies identify ATF4 as an anabolic transcription factor that
      is repressed by glucocorticoids and induced by insulin. Insulin-mediated
      induction of ATF4 required the mammalian target of rapamycin complex 1, was
      required for the activation of a genetic program for the cellular uptake of
      essential amino acids and the synthesis of nonessential amino acids and aminoacyl
      tRNAs, and was coupled to the repression of Foxo-dependent genes needed for
      protein and lipid catabolism. These results suggest that ATF4 plays a central
      role in hormonal regulation of amino acid and protein anabolism by coupling amino
      acid uptake and synthesis, as well as the generation of charged tRNAs, to
      mammalian target of rapamycin complex 1-mediated mRNA translation.

PMID- 17430895
TI  - Scleraxis and NFATc regulate the expression of the pro-alpha1(I) collagen gene in
      tendon fibroblasts.
AB  - The combinatorial action of separate cis-acting elements controls the cell
      specific expression of type I collagen genes. In particular, we have shown that
      two short elements located between -3.2 and -2.3 kb and named TSE1 and TSE2 are
      needed for expression of the mouse COL1a1 gene in tendon fibroblasts. In this
      study, we analyzed the trans-acting factors binding to TSE1 and TSE2. Gel shift
      experiments showed that scleraxis (SCX), which is a basic helix-loop-helix
      transcription factor that is expressed selectively in tendon fibroblasts, binds
      TSE2, preferentially as a SCX/E47 heterodimer. In transfection experiments,
      overexpression of SCX and E47 strongly enhanced the activity of reporter
      constructs harboring either four copies of TSE2 cloned upstream of the COL1a1
      minimal promoter or a 3.2-kb segment of the COL1a1 proximal promoter. Analysis of
      TSE1 showed that it contains a consensus binding site for NFATc transcription
      factors. This led us to show that the NFATc4 gene is expressed in tendons of
      developing mouse limbs and in TT-D6 cells, a cell line that has characteristics
      of tendon fibroblasts. In gel shift assays, TSE1 bound NFATc proteins present in
      nuclear extracts from TT-D6 cells. In transfection experiments, overexpression of
      NFATc transactivated a reporter construct harboring four copies of TSE1 cloned
      upstream of the COL1a1 minimal promoter. By contrast, inhibition of the nuclear
      translocation of NFATc proteins in TT-D6 cells strongly inhibited the expression
      of the COL1a1 gene. Taken together, these results suggest that SCX and NFATc4
      cooperate to activate the COL1a1 gene specifically in tendon fibroblasts.

PMID- 17430896
TI  - Immobilization of bioactive fibroblast growth factor-2 into cubic proteinous
      microcrystals (Bombyx mori cypovirus polyhedra) that are insoluble in a
      physiological cellular environment.
AB  - The supramolecular architecture of the extracellular matrix and the disposition
      of its specific accessory molecules give rise to variable heterotopic signaling
      cues for single cells. Here we have described the successful occlusion of human
      fibroblast growth factor-2 (FGF-2) into the cubic inclusion bodies (FGF-2
      polyhedra) of the Bombyx mori cytoplasmic polyhedrosis virus (BmCPV). The
      polyhedra are proteinous cubic crystals of several microns in size that are
      insoluble in the extracellular milieu. Purified FGF-2 polyhedra were found to
      stimulate proliferation and phosphorylation of p44/p42 mitogen-activated protein
      kinase in cultured fibroblasts. Moreover, cellular responses were blocked by a
      synthetic inhibitor of the FGF signaling pathway, SU5402, suggesting that FGF-2
      polyhedra indeed act through FGF receptors. Furthermore, FGF-2 polyhedra retained
      potent growth stimulatory properties even after desiccation. We have demonstrated
      that BmCPV polyhedra microcrystals that occlude extracellular signaling proteins
      are a novel and versatile tool that can be employed to analyze cellular behavior
      at the single cell level.

PMID- 17430897
TI  - Heme oxygenase-1 protein localizes to the nucleus and activates transcription
      factors important in oxidative stress.
AB  - Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is an
      integral membrane protein of the smooth endoplasmic reticulum. However, we
      detected an HO-1 immunoreactive signal in the nucleus of cultured cells after
      exposure to hypoxia and heme or heme/hemopexin. Under these conditions, a faster
      migrating HO-1 immunoreactive band was enriched in nuclear extracts, suggesting
      that HO-1 was cleaved to allow nuclear entry. This was confirmed by the absence
      of immunoreactive signal with an antibody against the C terminus and the lack of
      a C-terminal sequence by gas chromatographymass spectrometry. Incubation with
      leptomycin B prior to hypoxia abolished nuclear HO-1 and the faster migrating
      band on Western analysis, suggesting that this process was facilitated by CRM1.
      Furthermore, preincubation with a cysteine protease inhibitor prevented nuclear
      entry of green fluorescent protein-labeled HO-1, demonstrating that protease
      mediated C-terminal cleavage was also necessary for nuclear transport of HO-1.
      Nuclear localization was also associated with reduction of HO activity. HO-1
      protein, whether it was enzymatically active or not, mediated activation of
      oxidant-responsive transcription factors, including activator protein-1.
      Nevertheless, nuclear HO-1 protected cells against hydrogen peroxide-mediated
      injury equally as well as cytoplasmic HO-1. We speculate that nuclear
      localization of HO-1 protein may serve to up-regulate genes that promote
      cytoprotection against oxidative stress.

PMID- 17430898
TI  - Interaction sites between the Slo1 pore and the NH2 terminus of the beta2
      subunit, probed with a three-residue sensor.
AB  - Calcium- and voltage-gated (BK) K(+) channels encoded by Slo1 play an essential
      role in nervous systems. Although it shares many common features with voltage
      dependent K(V) channels, the BK channel exhibits differences in gating and
      inactivation. Using a mutant in which FWI replaces three residues (FIW) in the
      NH(2) terminus of wild-type beta2-subunits, in conjunction with alanine-scanning
      mutagenesis of the Slo1 S6 segment, we identify that the NH(2) terminus of beta2
      subunits interacts with the residues near the cytosolic superficial mouth of BK
      channels during inactivation. The cytosolic blockers did not share the sites with
      NH(2) terminus of beta2-subunits. A novel blocking-inactivating scheme was
      proposed to account for the observed non-competition inactivation. Our results
      also suggest that the residue Ile-323 plays a dual role in interacting with the
      NH(2) terminus of beta2-subunits and modulating the gating of BK channels.

PMID- 17430899
TI  - Thermodynamic investigation of the role of contact residues of beta-lactamase
      inhibitory protein for binding to TEM-1 beta-lactamase.
AB  - We have determined the thermodynamics of binding for the interaction between TEM
      1 beta-lactamase and a set of alanine substituted contact residue mutants ofbeta
      lactamase-inhibitory protein (BLIP) using isothermal titration calorimetry. The
      binding enthalpies for these interactions are highly temperature dependent, with
      negative binding heat capacity changes ranging from -800 to -271 cal mol(-1) K(
      1). The isoenthalpic temperatures (at which the binding enthalpy is zero) of
      these interactions range from 5 to 38 degrees C. The changes in isoenthalpic
      temperature were used as an indicator of the changes in enthalpy and entropy
      driving forces, which in turn are related to hydrophobic and hydrophilic
      interactions. A contact residue of BLIP is categorized as a canonical residue if
      its alanine substitution mutant exhibits a change of isoenthalpic temperature
      matching the change of hydrophobicity because of the mutation. A contact position
      exhibiting a change in isoenthalpic temperature that does not match the change in
      hydrophobicity is categorized as an anti-canonical residue. Our experimental
      results reveal that the majority of residues where alanine substitution results
      in a loss of affinity are canonical (7 of 10), and about half of the residues
      where alanine substitutions have a minor effect are canonical. The interactions
      between TEM-1beta-lactamase and BLIP canonical contact residues contribute
      directly to binding free energy, suggesting potential anchoring sites for binding
      partners. The anti-canonical behavior of certain residues may be the result of
      mutation-induced modifications such as structural rearrangements affecting
      contact residue configurations. Structural inspection of BLIP suggests that the
      Lys(74) side chain electrostatically holds BLIP loop 2 in position to bind to TEM
      1 beta-lactamase, explaining a large loss of entropy-driven binding energy of the
      K74A mutant and the resulting anti-canonical behavior. The anti-canonical
      behavior of the W150A mutant may also be due to structural rearrangements.
      Finally, the affinity enhancing effect of the contact residue mutant Y50A may be
      due to energetic coupling interactions between Asp(49) and His(41).

PMID- 17430900
TI  - A beta-1,2-xylosyltransferase from Cryptococcus neoformans defines a new family
      of glycosyltransferases.
AB  - Cryptococcus neoformans is an opportunistic fungal pathogen characterized by a
      prominent polysaccharide capsule that envelops the cell. Although this capsule is
      dispensable for in vitro growth, its presence is essential for virulence. The
      capsule is primarily made of two xylose-containing polysaccharides,
      glucuronoxylomannan and galactoxylomannan. There are likely to be multiple
      xylosyltransferases (XTs) involved in capsule synthesis, and the activities of
      these enzymes are potentially important for cryptococcal virulence. A beta-1,2
      xylosyltransferase with specificity appropriate for capsule synthesis was
      purified approximately 3000-fold from C. neoformans, and the corresponding gene
      was identified and cloned. This sequence conferred XT activity when expressed in
      Saccharomyces cerevisiae, which lacks endogenous XT activity. The gene, termed
      CXT1 for cryptococcal xylosyltransferase 1, encodes a 79-kDa type II membrane
      protein with an N-linked glycosylation site and two DXD motifs. These latter
      motifs are believed to coordinate divalent cation binding in the activity of
      glycosyltransferases. Site-directed mutagenesis of one DXD motif abolished Cxt1p
      activity, even though this activity does not depend on the addition of a divalent
      cation. This may indicate a novel catalytic mechanism for glycosyl transfer. Five
      homologs of Cxt1p were found in the genome sequence of C. neoformans and 34
      within the sequences of other fungi, although none were found in other organisms.
      Many of the homologous proteins are similar in size to Cxt1p, and all are
      conserved with respect to the essential DXD motif. These proteins represent a new
      family of glycosyltransferases, found exclusively within the fungal kingdom.

PMID- 17430901
TI  - Mass spectrometry reveals the missing links in the assembly pathway of the
      bacterial 20 S proteasome.
AB  - The 20 S proteasome is an essential proteolytic particle, responsible for
      degrading short-lived and abnormal intracellular proteins. The 700-kDa assembly
      is comprised of 14 alpha-type and 14 beta-type subunits, which form a cylindrical
      architecture composed of four stacked heptameric rings (alpha7beta7beta7alpha7).
      The formation of the 20 S proteasome is a complex process that involves a cascade
      of folding, assembly, and processing events. To date, the understanding of the
      assembly pathway is incomplete due to the experimental challenges of capturing
      short-lived intermediates. In this study, we have applied a real-time mass
      spectrometry approach to capture transient species along the assembly pathway of
      the 20 S proteasome from Rhodococcus erythropolis. In the course of assembly, we
      observed formation of an early alpha/beta-heterodimer as well as an unprocessed
      half-proteasome particle. Formation of mature holoproteasomes occurred in concert
      with the disappearance of half-proteasomes. We also analyzed the beta-subunits
      before and during assembly and reveal that those with longer propeptides are
      incorporated into half- and full proteasomes more rapidly than those that are
      heavily truncated. To characterize the preholoproteasome, formed by docking of
      two unprocessed half-proteasomes and not observed during assembly of wild type
      subunits, we trapped this intermediate using a beta-subunit mutational variant.
      In summary, this study provides evidence for transient intermediates in the
      assembly pathway and reveals detailed insight into the cleavage sites of the
      propeptide.

PMID- 17430902
TI  - Lysophosphatidic acid facilitates proliferation of colon cancer cells via
      induction of Kruppel-like factor 5.
AB  - Among the multiple cellular effects mediated by lysophosphatidic acid (LPA), the
      effect on cell proliferation has extensively been investigated. A recent study
      showed that LPA-mediated proliferation of colon cancer cells requires activation
      of beta-catenin. However, the majority of colon cancer cells have deregulation of
      the Wnt/beta-catenin pathway. This prompted us to hypothesize the presence of
      additional pathway(s) activated by LPA resulting in an increase in the
      proliferation of colon cancer cells. Kruppel-like factor 5 (KLF5) is a
      transcriptional factor highly expressed in the crypt compartment of the
      intestinal epithelium. In this work, we investigated a role of KLF5 in LPA
      mediated proliferation. We show that LPA stimulated the expression levels of KLF5
      mRNA and protein in colon cancer cells and this stimulation was mediated by
      LPA(2) and LPA(3). Silencing of KLF5 expression by small interfering RNA
      significantly attenuated LPA-mediated proliferation of SW480 and HCT116 cells.
      LPA-mediated KLF5 induction was partially blocked by inhibition of the mitogen
      activated protein kinase kinase and protein kinase C-delta. Moreover, we observed
      that LPA regulates KLF5 expression via eukaryotic elongation factor 2 kinase
      (eEF2k). Inhibition of calmodulin or silencing of eEF2k blocked the stimulation
      in KLF5 expression. Knockdown of eEF2k specifically inhibited KLF5 induction by
      LPA but not by fetal bovine serum or phorbol 12-myristate 13-acetate. These
      results identify KLF5 as a target of LPA-mediated signaling and suggest a role of
      KLF5 in promoting proliferation of intestinal epithelia in response to LPA.

PMID- 17430904
TI  - The integrin binding site 2 (IBS2) in the talin rod domain is essential for
      linking integrin beta subunits to the cytoskeleton.
AB  - Talin1 is a large cytoskeletal protein that links integrins to actin filaments
      through two distinct integrin binding sites, one present in the talin head domain
      (IBS1) necessary for integrin activation and a second (IBS2) that we have
      previously mapped to talin residues 1984-2113 (fragment J) of the talin rod
      domain (1 Tremuth, L., Kreis, S., Melchior, C., Hoebeke, J., Ronde, P., Plancon,
      S., Takeda, K., and Kieffer, N. (2004) J. Biol. Chem. 279, 22258-22266), but
      whose functional role is still elusive. Using a bioinformatics and cell biology
      approach, we have determined the minimal structure of IBS2 and show that this
      integrin binding site corresponds to 23 residues located in alpha helix 50 of the
      talin rod domain (residues 2077-2099). Alanine mutation of 2 highly conserved
      residues (L2094A/I2095A) within this alpha helix, which disrupted the alpha
      helical structure of IBS2 as demonstrated by infrared spectroscopy and limited
      trypsin proteolysis, was sufficient to prevent in vivo talin fragment J targeting
      to alphaIIbbeta3 integrin in focal adhesions and to inhibit in vitro this
      association as shown by an alphaIIbbeta3 pulldown assay. Moreover, expression of
      a full-length mouse green fluorescent protein-talin LI/AA mutant in mouse talin1(
      /-) cells was unable to rescue the inability of these cells to assemble focal
      adhesions (in contrast to green fluorescent protein-talin wild type) despite the
      presence of IBS1. Our data provide the first direct evidence that IBS2 in the
      talin rod is essential to link integrins to the cytoskeleton.

PMID- 17430903
TI  - Expression of allosteric linkage between the sodium ion binding site and exosite
      I of thrombin during prothrombin activation.
AB  - The specificity of thrombin for procoagulant and anticoagulant substrates is
      regulated allosterically by Na+. Ordered cleavage of prothrombin (ProT) at Arg320
      by the prothrombinase complex generates proteolytically active, meizothrombin
      (MzT), followed by cleavage at Arg271 to produce thrombin and fragment 1.2. The
      alternative pathway of initial cleavage at Arg271 produces the inactive zymogen
      form, the prethrombin 2 (Pre 2).fragment 1.2 complex, which is cleaved
      subsequently at Arg320. Cleavage at Arg320 of ProT or prethrombin 1 (Pre 1)
      activates the catalytic site and the precursor form of exosite I (proexosite I).
      To determine the pathway of expression of Na+-(pro)exosite I linkage during ProT
      activation, the effects of Na+ on the affinity of fluorescein-labeled hirudin-(54
      65) ([5F]Hir-(54-65)(SO-3)) for the zymogens, ProT, Pre 1, and Pre 2, and for the
      proteinases, MzT and MzT-desfragment 1 (MzT(-F1)) were quantitated. The zymogens
      showed no significant linkage between proexosite I and Na+, whereas cleavage at
      Arg320 caused the affinities of MzT and MzT(-F1) for [5F]Hir-(54-65)(SO-3) to be
      enhanced by Na+ 8- to 10-fold and 5- to 6-fold, respectively. MzT and MzT(-F1)
      showed kinetically different mechanisms of Na+ enhancement of chromogenic
      substrate hydrolysis. The results demonstrate for the first time that MzT is
      regulated allosterically by Na+. The results suggest that the distinctive
      procoagulant substrate specificity of MzT, in activating factor V and factor VIII
      on membranes, and the anticoagulant, membrane-modulated activation of protein C
      by MzT bound to thrombomodulin are regulated by Na+-induced allosteric
      transition. Further, the Na+ enhancement in MzT activity and exosite I affinity
      may function in directing the sequential ProT activation pathway by accelerating
      thrombin formation from the MzT fast form.

PMID- 17430905
TI  - Hot topic: Fatty acid and conjugated linoleic acid (CLA) isomer composition of
      commercial CLA-fortified dairy products: evaluation after processing and storage.
AB  - Conjugated linoleic acid (CLA) exerts a strong positive influence on human health
      but intake of these fatty acids is typically too low, and increased consumption
      of CLA is recommended. A good way to raise the CLA content in the diet without a
      radical change in eating habits seems to be the enrichment of commonly consumed
      food products with CLA supplements. This study analyzed the total fatty acid
      content and the CLA isomer composition of 6 commercially available CLA-fortified
      dairy products during processing and 10 wk of refrigerated storage. Research was
      carried out by combining gas chromatography and silver-ion HPLC. The tested
      samples were a CLA oil supplement, and several skim milk dairy products fortified
      with the supplement (milk, milk powder, fermented milk, yogurt, fresh cheese, and
      milk-juice blend). The CLA oil supplement was added such that the consumer
      received 2.4 g/d of CLA by consuming 2 servings. The predominant isomers present,
      C18:2 cis-9, trans-11 CLA and C18:2 cis-10, trans-12 CLA, were in at a similar
      ratio, which ranged from 0.97 to 1.05. These major isomers were not significantly
      affected by processing but a decrease in total CLA in fresh cheese samples was
      detected after 10 wk of refrigerated storage. Refrigerated storage and thermal
      treatment resulted in significant decreases or disappearance of some of the minor
      CLA isomers and a significant increase of trans, trans isomers from both cis,
      trans, trans, cis, and cis, cis isomers especially in CLA-fortified milk powder
      but also in fermented milk, yogurt, and milk-juice blend.

PMID- 17430906
TI  - Identification of the characteristics that drive consumer liking of butter.
AB  - This study identified and explored the sensory characteristics that drive
      consumer liking of butter. A trained descriptive panel evaluated 27 commercial
      butters using a defined sensory language. Two focus groups were conducted with
      butter consumers to gain an understanding of consumer use and consumption habits.
      Six representative butters and 2 vegetable oil spreads were selected for consumer
      acceptance testing. Both internal and external preference mapping techniques were
      applied to interpret consumer data. Key discriminating sensory characteristics of
      butters included color intensity; diacetyl, cooked, grassy, and milk fat flavors;
      and salty taste. From focus groups and quantitative consumer testing, the key
      butter features were a desirable flavor and a natural image. Negative aspects
      included price and cholesterol. Five consumer clusters with distinct butter and
      spread flavor likes and dislikes were identified. Butter is a desirable product
      to consumers. Sensory expectations of butter vary among consumers, and butters
      with specific sensory characteristics could be marketed to specific target market
      segments.

PMID- 17430907
TI  - Proteolysis in Mozzarella cheeses manufactured by different industrial processes.
AB  - The objective of the present study was to investigate the influence of stretching
      temperature, fat content, and time of brining on proteolysis during ripening of
      Mozzarella cheeses. Seventeen cheese-making experiments (batches) were carried
      out on an industrial scale on successive days, following the standard procedure
      with some modifications. Fat content of cheese milk, temperature at the
      stretching step, and time of brining varied from one batch to another as required
      by the experimental design, outlined by a surface response model. Proteolysis was
      assessed during ripening of samples, which was prolonged for at least 3 mo, by
      means of electrophoresis, nitrogen fractions, and soluble peptide mapping. The
      amount of soluble nitrogen at pH 4.6 was not significantly different in cheeses
      obtained by diverse procedures, but it increased during ripening of all samples.
      This result was coincident with the breakdown of alpha(s1)- and beta-caseins
      evidenced by electrophoresis, which reached similar extents at late stages of
      ripening, regardless of the cheese-making process. Multivariate analysis on
      soluble peptide profiles obtained by liquid chromatography also detected sample
      grouping according to ripening time, but did not evidence any separation caused
      by the cheese-making technology. We concluded that the changes in the cheese
      making process assayed in this work were insufficient to produce significant
      differences in proteolysis of the cheeses. Ripening time had more influence on
      proteolysis of Mozzarella cheeses than any other assayed variable.

PMID- 17430908
TI  - Effects of high pressure on proteolytic enzymes in cheese: relationship with the
      proteolysis of ewe milk cheese.
AB  - Ewe milk cheeses were submitted to 200, 300, 400, and 500 MPa (2P to 5P) at 2
      stages of ripening (after 1 and 15 d of manufacturing; P1 and P15). The high
      pressure-treated cheeses showed a more important hydrolysis of beta-casein than
      control and 2P1 cheeses. Degradation of alpha(s1)-casein was more important in
      3P1, 4P1, and P15 cheeses than control and 2P1 cheeses. The 5P1 cheeses exhibited
      the lowest degradation of alpha(s)-caseins, probably as a consequence of the
      inactivation of residual chymosin. Treatment at 300 MPa applied on the first day
      of ripening increased the peptidolytic activity, accelerating the secondary
      proteolysis of cheeses. The 3P1 cheeses had extensive peptide degradation and the
      highest content of free amino acids. Treatments at 500 MPa, however, decelerated
      the proteolysis of cheeses due to a reduction of microbial population and
      inactivation of enzymes.

PMID- 17430909
TI  - Innovative active packaging systems to prolong the shelf life of Mozzarella
      cheese.
AB  - In this work the effectiveness of different antimicrobial packaging systems on
      the microbial quality decay kinetics during storage of Mozzarella cheese was
      evaluated. Lemon extract, at 3 different concentrations, was used as active
      agent, in combination with brine and with a gel solution made of sodium alginate.
      Shelf life tests were run at 15 degrees C to simulate thermal abuse. The cell
      load of spoilage and dairy functional microorganisms were monitored at regular
      time intervals during storage. By fitting the experimental data through a
      modified version of the Gompertz equation, the shelf life of dairy products
      packaged in the different systems was calculated. Results show an increase in the
      shelf life of all active packaged Mozzarella cheeses, confirming that the
      investigated substance may exert an inhibitory effect on the microorganisms
      responsible for spoilage phenomena without affecting the functional microbiota of
      the product.

PMID- 17430910
TI  - Microfiltration of buttermilk and washed cream buttermilk for concentration of
      milk fat globule membrane components.
AB  - Buttermilk, the by-product from butter manufacture, has gained much attention
      lately because of the application potential of its milk fat globule membrane
      (MFGM) components as health ingredients. Microfiltration (MF) has been studied
      for buttermilk fractionation because of its ability to separate particles from
      dissolved solutes. However, the presence in this by-product of skim milk solids,
      especially casein micelles, restricts concentration of MFGM. The use of cream
      washed with skim milk ultrafiltrate to produce buttermilk with lower casein
      content was studied as well as fractionation of this buttermilk by MF. Results
      have shown that washing the cream prior to churning yields buttermilk with 74%
      less protein than normal cream buttermilk. Analysis of the protein profile of
      washed cream buttermilk revealed that caseins and whey proteins were the main
      classes of proteins removed. The MF of washed cream buttermilk resulted in
      permeation fluxes 2-fold higher than with normal cream buttermilk. The second
      separation of the cream induced high losses of phospholipids in the skim phase.
      However, retention of remaining phospholipids in washed cream buttermilk by the
      MF membrane was higher resulting in a phospholipids concentration factor 66%
      higher than that of normal cream buttermilk. The results presented in this study
      highlight the impact of casein micelles on the separation of MFGM components as
      well as their effect on permeation flux during MF.

PMID- 17430911
TI  - Use of whey permeate for cultivating Ganoderma lucidum mycelia.
AB  - A novel approach to utilizing whey permeate, the cultivation of mycelia of the
      edible mushroom Ganoderma lucidum, is introduced. The major objective of this
      research was to use whey permeate as an alternative growth medium for the
      cultivation of mycelia of edible mushroom G. lucidum and to find an optimum
      condition for solid-state cultivation. Response surface analysis was applied to
      determine the combination of substrate concentration (25 to 45 g of lactose/L),
      pH (3.5 to 5.5), and temperature (25 to 35 degrees C) resulting in a maximal
      mycelial growth. The radial extension rates, estimated by measuring the diameters
      of growing colonies on the Petri dishes, were used as the growth of the mycelia
      at different conditions. In the model, pH and temperature significantly affected
      mycelial growth, but lactose concentration did not. The condition predicted to
      maximize the radial extension rate of 17.6 +/- 0.4 mm/d was determined to be pH
      4.4 and temperature 29.4 degrees C. Therefore, the results suggest that whey
      permeate could be utilized as a growth substrate for the cultivation of mycelia
      from the edible mushroom G. lucidum, enhancing the use of this by-product by the
      cheese manufacturing industry.

PMID- 17430913
TI  - Influence of calcium salt supplementation on calcium equilibrium in skim milk
      during pH cycle.
AB  - Calcium is a mineral essential for humans, especially for bone constitution. Yet
      most of the worldwide population does not satisfy their Ca needs. Hence, Ca
      supplementation is of major importance, even in western countries where some
      specific populations at risk do not satisfy the recommended daily intake of Ca.
      More than 70% of dietary Ca comes from dairy products. Calcium supplementation of
      naturally Ca-rich sources such as skim milk is then of special interest. To our
      knowledge, few data are available concerning milk Ca (MC) supplementation of
      milk, particularly when followed by pH cycle. In this paper, MC supplementation
      is studied and compared with Ca chloride (CC) supplementation as a well-known
      source of Ca. The effect of Ca salt supplementation followed by pH cycle was
      studied in reconstituted skim milk. Calcium supplementation was carried out with
      CC and MC at 25 mmol of Ca/kg of skim milk. Ionized Ca concentration and
      turbidity variations were followed in situ by Ca ion selective electrode and
      turbidimetry using light reflection. From normalized data on ionized Ca
      concentration and turbidity vs. pH, it appeared that hysteresis areas were
      smaller for CC-supplemented milk, whereas unsupplemented milk and MC-supplemented
      milk behaved similarly. For these 3 dairy systems, pH cycles to pH 5.0 led to a
      larger hysteresis area than pH cycles to pH 5.5. The shrinkage of the hysteresis
      area could be interpreted as a reinforcement of casein micelles with Ca ions over
      the pH cycle.

PMID- 17430912
TI  - Enzymatic production of infant milk fat analogs containing palmitic acid:
      optimization of reactions by response surface methodology.
AB  - Infant milk fat analogs resembling human milk fat were synthesized by an
      enzymatic interesterification between tripalmitin, coconut oil, safflower oil,
      and soybean oil in hexane. A commercially immobilized 1,3-specific lipase,
      Lipozyme RM IM, obtained from Rhizomucor miehei was used as a biocatalyst. The
      effects of substrate molar ratio, reaction time, and incubation temperature on
      the incorporation of palmitic acid at the sn-2 position of the triacylglycerols
      were investigated. A central composite design with 5 levels and 3 factors
      consisting of substrate ratio, reaction temperature, and incubation time was used
      to model and optimize the reaction conditions using response surface methodology.
      A quadratic model using multiple regressions was then obtained for the
      incorporation of palmitic acid at the sn-2 positions of glycerols as the
      response. The coefficient of determination (R2) value for the model was 0.845.
      The incorporation of palmitic acid appeared to increase with the decrease in
      substrate molar ratio and increase in reaction temperature, and optimum
      incubation time occurred at 18 h. The optimal conditions generated from the model
      for the targeted 40% palmitic acid incorporation at the sn-2 position were 3
      mol/mol, 14.4 h, and 55 degrees C; and 2.8 mol/mol, 19.6 h, and 55 degrees C for
      substrate ratio (moles of total fatty acid/moles of tripalmitin), time, and
      temperature, respectively. Infant milk fat containing fatty acid composition and
      sn-2 fatty acid profile similar to human milk fat was successfully produced. The
      fat analogs produced under optimal conditions had total and sn-2 positional
      palmitic acid levels comparable to that of human milk fat.

PMID- 17430914
TI  - Factors regulating cheese shreddability.
AB  - Two sets of cheeses were evaluated to determine factors that affect shred
      quality. The first set of cheeses was made up of 3 commercial cheeses, Monterey
      Jack, Mozzarella, and process. The second set of cheeses was made up of 3
      Mozzarella cheeses with varying levels of protein and fat at a constant moisture
      content. A shred distribution of long shreds, short shreds, and fines was
      obtained by shredding blocks of cheese in a food processor. A probe tack test was
      used to directly measure adhesion of the cheese to a stainless-steel surface.
      Surface energy was determined based on the contact angles of standard liquids,
      and rheological characterization was done by a creep and recovery test. Creep and
      recovery data were used to calculate the maximum and initial compliance and
      retardation time. Shredding defects of fines and adhesion to the blade were
      observed in commercial cheeses. Mozzarella did not adhere to the blade but did
      produce the most fines. Both Monterey Jack and process cheeses adhered to the
      blade and produced fines. Furthermore, adherence to the blade was correlated
      positively with tack energy and negatively with retardation time. Mozzarella
      cheese, with the highest fat and lowest protein contents, produced the most fines
      but showed little adherence to the blade, even though tack energy increased with
      fat content. Surface energy was not correlated with shredding defects in either
      group of cheese. Rheological properties and tack energy appeared to be the key
      factors involved in shredding defects.

PMID- 17430915
TI  - An economic evaluation of freeze-dried kefir starter culture production using
      whey.
AB  - An economic study is presented in which industrial-scale production of freeze
      dried kefir starter culture is discussed based on results on a laboratory scale.
      Industrial scale-up was based on a 3-step process using 3 bioreactors of 100,
      3,000, and 30,000 L for 300 kg of freeze-dried culture/d of plant capacity. The
      major cost component of the total investment was the freeze-drying machinery,
      which consisted of 57% of the total investment. Production cost was reduced from
      15.4 euros/kg ($18.5/kg) to 2.9 euros/kg ($3.5/kg) when the production capacity
      was increased from 30 to 900 kg/d. An economic analysis revealed a 3.5-fold
      increase in production cost compared with the corresponding production cost of
      the wet product, with an added value of up to 10.8 x 10(9) euros ($13.0 x 10(9))
      within the European Union.

PMID- 17430916
TI  - Alternatives for improving physical, chemical, and sensory characteristics of
      goat cheeses: the use of arid-land forages in the diet.
AB  - To establish the effect of an alternative diet on the quality of Majorero cheese,
      the basic physicochemical parameters, fatty acid profile, and sensory
      characteristics were studied. Two groups of 20 Majorero goats were fed 2
      different diets: a forage diet (DF), which had a high ratio of long fiber to
      concentrates (65:35), and a concentrate diet (DC), with a low ratio of long fiber
      to concentrates (35:65). The DF dietary fiber was supplied by native forages
      adapted to arid land. A total of 42 Majorero goat cheeses were used for this
      study: 21 in the DF group and 21 in the DC group. Seven cheeses from each group
      were tested after 2, 15, and 60 d of ripening. The milk produced by goats fed the
      DF diet had a higher fat concentration. No significant differences were observed
      in the milk fatty acid profile. The diet affected the chemical composition of the
      cheese in pH and fat content, and fat was significantly higher in cheeses made
      from DF milk than those from DC milk. Dietary characteristics had important
      effects on the medium-chain fatty acid composition (C6 to C14) of the cheese fat,
      giving DF cheeses the specific goat's milk flavor that is sought after for this
      type of cheese. The fatty acid composition (%) differed substantially among
      different ripening times. The DF cheeses were more appreciated by the panelists,
      as they had a greater variety of odors and flavors than the DC cheeses. The DF
      hard cheeses were described as having vegetable and fruity tones as well as tones
      of hay and dried fruit.

PMID- 17430917
TI  - Front-face fluorescence measurement of photosensitizers and lipid oxidation
      products during the photooxidation of butter.
AB  - This paper shows that fluorescence spectroscopy can measure both degradation of
      photosensitizers and formation of lipid oxidation products in light-exposed
      butter. The photosensitizers were already notably degraded after 4 h of light
      exposure, whereas fluorescent lipid oxidation products were detected after 5 d.
      The fluorescence measurements were highly correlated with sensory assessments of
      acidic and rancid flavor. Photosensitizer degradation is therefore a promising
      indirect indicator of the onset of lipid oxidation in butter. Sensory analysis
      and measurement of peroxide value showed that the level of lipid oxidation was
      significantly higher for butter stored in air compared with butter stored in
      nitrogen (N2). This might be explained by the formation of singlet oxygen from
      direct photooxidation and type II photosensitized oxidation. Addition of the
      singlet oxygen quencher beta-carotene reduced the rancid flavor intensity in the
      air and N2 packages from 9.0 to 4.9 and from 6.5 to 4.7, respectively. Results
      indicate that lipid oxidation in the butter stored in N2 was mainly caused by
      type I photosensitized reactions, because addition of beta-carotene had little
      effect on the rancid flavor intensity.

PMID- 17430918
TI  - Stability of the biodiversity of the surface consortia of Gubbeen, a red-smear
      cheese.
AB  - A total of 1,052 bacteria and 828 yeasts were isolated from the surface flora of
      6 batches of Gubbeen cheese made in 1996-1997 and 2002-2003. Stability of the
      microflora was evaluated over time and also during ripening at 4, 10, and 16 d
      (batches 4, 5, and 6) or at 4, 16, 23, and 37 d (batches 1, 2, and 3). Bacteria
      were identified using pulsed-field gel electrophoresis, repetitive extragenic
      palindromic-PCR, and 16S rRNA gene sequencing, and yeasts were identified by
      Fourier transform infrared spectroscopy. The bacteria included at least 17
      species, of which the most common were Staphylococcus saprophyticus (316
      isolates), Corynebacterium casei (248 isolates), Brevibacterium aurantiacum (187
      isolates), Corynebacterium variabile (146 isolates), Microbacterium gubbeenense
      (55 isolates), Staphylococcus equorum/cohnii (31 isolates), and Psychrobacter
      spp. (26 isolates). The most common yeasts were Debaryomyces hansenii (624
      isolates), Candida catenulata (135 isolates), and Candida lusitaniae (62
      isolates). In all batches of cheese except batch 2, a progression of bacteria was
      observed, with staphylococci dominating the early stages of ripening and
      coryneforms the later stages. No progression of yeast was found. Pulsed-field gel
      electrophoresis showed that several different strains of the 5 important species
      of bacteria were present, but generally only one predominated. The commercial
      strains used for smearing the cheese were recovered, but only in very small
      numbers early in ripening. Four species, B. aurantiacum, C. casei, C. variabile,
      and Staph. saprophyticus, were found on all batches of cheese, but their relative
      importance varied considerably. The results imply that significant variation
      occurs in the surface microflora of cheese.

PMID- 17430919
TI  - Trans-9, cis-11 conjugated linoleic acid reduces milk fat synthesis in lactating
      dairy cows.
AB  - Under certain dietary situations, rumen biohydrogenation results in the
      production of unique fatty acids that inhibit milk fat synthesis. The first of
      these to be identified was trans-10, cis-12 conjugated linoleic acid (CLA), but
      others are postulated to contribute to diet-induced milk fat depression (MFD).
      Our objective was to examine the potential role of trans-9, cis-11 CLA in the
      regulation of milk fat. In a preliminary study, we used gas-liquid and high
      performance liquid chromatography techniques to examine milk fat samples from a
      diet-induced MFD study and found that an increase in trans-9, cis-11 CLA
      corresponded to the decrease in milk fat yield. We investigated this further
      using a CLA enrichment of 9, 11 isomers to examine the biological effect of trans
      9, cis-11 CLA on milk fat synthesis. Four rumen-fistulated Holstein cows were
      randomly assigned in a 4 x 4 Latin square experiment involving 5-d treatment
      periods and abomasal infusion of 1) ethanol (control), 2) a 9, 11 CLA mix
      (containing 32% trans-9, cis-11, 29% cis-9, trans-11, and 17% trans-9, trans-11),
      3) a trans-9, trans-11 CLA supplement, and 4) a trans-10, cis-12 CLA supplement
      (positive control). The trans-9, trans-11 CLA and trans-10, cis-12 CLA
      supplements were of high purity (>90%), and all supplements were infused at a
      rate to provide 5 g/d of the CLA isomer of interest. Milk yield and dry matter
      intake did not differ among treatments. Compared with the control treatment, milk
      fat yield was reduced by 15% for the 9, 11 CLA mixture and by 27% for the trans
      10, cis-12 CLA treatment. We also found that trans-9, trans-11 CLA had no effect
      on milk fat yield, and previous research has shown that milk fat yield is
      unaltered when cows are infused with cis-9, trans-11 CLA. When all treatments
      were considered, results suggested that trans-9, cis-11 was the CLA isomer in the
      9, 11 CLA mix responsible for the reduction in milk fat synthesis, although the
      magnitude was less than that observed for trans-10, cis-12 CLA. Interestingly,
      trans-9, trans-11 CLA altered the milk fat desaturase index, further
      demonstrating that alterations in desaturase can occur independently of effects
      on milk fat synthesis. Overall, our investigations identified that an increase in
      milk fat content of trans-9, cis-11 CLA was associated with diet-induced MFD and
      provided evidence of a role for this isomer in MFD based on the 15% reduction in
      milk fat yield with abomasal infusion of a CLA enrichment that supplied 5 g/d of
      trans-9, cis-11 CLA.

PMID- 17430920
TI  - Technical note: Effect of sampling protocol on plasma nonesterified fatty acid
      concentration in dairy cows.
AB  - The objective of these experiments was to determine effects of sampling protocol
      on plasma nonesterified fatty acid (NEFA) concentration. In experiment 1, 8
      nonlactating, nongestating dairy cows were blood sampled from a jugular vein
      catheter (basal, 0 min), moved to an exercise lot for 15 min, returned to
      stanchions, and sampled immediately and at 5, 15, 30, 60, and 120 min following
      return to their stalls. Following 15 min of exercise, plasma NEFA concentration
      increased, peaking at 5 min (225 microEq/L) and returning to basal (84 microEq/L)
      by 30 min (110 microEq/L). Cows were then moved to box stalls overnight, and 24 h
      after the basal sample, they were locked up and sampled again. Housing cows in a
      box stall overnight and locking them in headlocks increased plasma NEFA
      concentration (184 microEq/L). In a second experiment at a large free-stall
      commercial dairy, 11 late-gestation nonlactating dairy cows were locked in
      headlocks at feeding, blood was sampled from the coccygeal artery or vein (0
      min), and cows were then released and allowed to finish eating and return to
      their stalls. Cows were then herded to headlocks and sampled immediately at 120
      min after initial sampling and at 135, 150, and 180 min. Plasma NEFA
      concentration was highest at initial lockup (0 min; 284 microEq/L), lowest at 180
      min (178 microEq/L), and intermediate at time points in between. A second group
      of 10 late-gestation nonlactating dairy cows were locked in headlocks at feeding,
      and blood was sampled immediately and at 5, 15, 30, and 60 min. Plasma NEFA
      concentration was highest 15 min after being placed in headlocks and lowest 60
      min after lockup (221 and 113 microEq/L, respectively). At each time point in
      experiments 1 and 2, a behavior score was given (1 to 10; 1 = calm; 10 =
      extremely excited). In both experiments, there was a significant correlation
      between the plasma NEFA concentration and behavior score. In conclusion, plasma
      NEFA concentration was affected by sampling protocol.

PMID- 17430921
TI  - Interaction of somatic cell count and quarter milk flow patterns.
AB  - Milk flow parameters at udder and quarter levels were studied in relation to
      somatic cell count (SCC) and other risk factors for mastitis (bimodality,
      duration of decline, and duration of overmilking phase). Thirty-eight Holstein
      cows in their first to sixth lactations were investigated during 10 mo of
      lactation. Monthly milk samples were collected for SCC during morning milking.
      Quarter and udder milk flows were recorded daily. A cow was included if one
      quarter was found to have an SCC higher than 200 x 10(3) cells/mL. A total of
      3,262 quarter milk flow curves and 804 udder milk flow curves from 22 cows (6
      primiparous and 16 multiparous) were selected and evaluated. Selected data for
      milk flow profiles in relation to SCC represented 5 consecutive morning milkings
      around the time of milk sampling (sampling on d 3). A total of 661 milk samples
      were analyzed. At both the udder and quarter levels milk yield was reduced in
      groups with increased SCC. Quarters with high SCC (> 500 x 10(3) cells/mL) had
      lower peak flow rate and longer overmilking phases compared with quarters with
      low SCC (< 200 x 10(3) cells/mL). There was a tendency for a longer duration of
      the decline phase in quarters with high SCC but no effect was observed at the
      udder level. There were longer declines in bimodal milk flows at the quarter, but
      not at the udder, level. Also, quarters with bimodality had longer overmilking
      phases. The duration of the decline phases at the quarter level influenced all
      measured parameters except the duration of the increase phase. The quarters with
      a longer duration of the decline phase (> or = 80 s) had greater SCC and peak
      flow rate but had lower milk yield compared with quarters with a shorter duration
      of the decline phase (< 27 s). Duration of the overmilking phase influenced all
      measured parameters except SCC. We conclude that for good udder health, the
      duration of the decline phase at the quarter level should be considered for
      milking parameters and udder preparation before milking.

PMID- 17430922
TI  - Effect of a biological response modifier on expression of growth factors and
      cellular proliferation at drying off.
AB  - Agents that increase natural protective mechanisms have been proposed for the
      prevention and treatment of intramammary infections. Staphylococcus aureus is a
      major pathogen causing primarily subclinical chronic mastitis that responds
      poorly to antibiotic therapy. The objectives of this study were to describe the
      effects of a single intramammary infusion of a lipopolysaccharide-based
      biological response modifier (BRM) on mammary epithelial cellular proliferation
      and expression of insulin-like growth factor-I (IGF-I) and vascular endothelial
      growth factor (VEGF) in uninfected and Staph. aureus-infected bovine mammary
      glands during involution. Three groups of 12 cows, 6 Staph. aureus-infected and 6
      uninfected, were infused with BRM or placebo in 2 mammary quarters and killed at
      7, 14, and 21 d of involution. The proportion of infected quarters, mammary cell
      proliferation, and IGF-I and VEGF expression were evaluated. Biological response
      modifier treatment decreased the proportion of Staph. aureus-infected mammary
      quarters at 7 d of involution, but a similar number of isolations were observed
      at 14 and 21 d of involution in either treated or control quarters. The
      percentage of proliferating mammary epithelial cells was higher in infected than
      uninfected quarters at every observation period, irrespective of the treatment
      administered, whereas uninfected BRM-treated quarters showed increased cell
      proliferation at 7 d of involution. Insulin-like growth factor-I expression in
      uninfected quarters was not affected by treatment and showed a decrease at 21 d
      of involution. Expression of IGF-I was greater in infected than uninfected
      quarters at every observation period, irrespective of the treatment received.
      Expression of VEGF was greater in BRM-treated uninfected quarters at 7 d of
      involution compared with controls. In infected quarters, VEGF expression was
      lowest in BRM-treated quarters at 7 d of involution and increased throughout the
      observation period. Conversely, untreated infected quarters showed the highest
      VEGF expression at 7 d and decreased at 21 d of involution. Mammary cell
      proliferation and expression of IGF-I and VEGF were increased in Staph. aureus
      infected quarters. Increased mammary cell proliferation and VEGF expression were
      observed in BRM-treated quarters during the first week of involution.

PMID- 17430923
TI  - Short communication: Usage of mechanical brushes by lactating dairy cows.
AB  - The objective of this experiment was to investigate how the provision of a
      mechanical brush affects the grooming (scratching) behavior of group-housed dairy
      cattle. To do this, we compared the grooming behavior of 72 dairy cows, split
      into 6 groups of 12, in the absence of a brush (control) and when provided with a
      mechanical brush (experimental). We analyzed the duration and frequency of
      scratching on pen objects (wall and water trough) and on the mechanical brush
      between the control and experimental treatments. Further, we compared the
      relative frequency of scratching on parts of the cow's body (head, neck, back,
      tail, and thigh) between the control and experimental treatments. Within 24 h of
      installation of the mechanical brush, 56.9% of the cows utilized the brush.
      Within 7 d, 93.0% of cows used the brush, and by the end of the treatment period,
      all but one of the cows had used the brush. When the mechanical brush was added
      to the pen, cows dramatically increased the total time spent scratching by 508%
      and the frequency of scratching events by 226%. These increases were primarily
      driven by use of the mechanical brush, which accounted for 91.1% of total
      scratching time and 79.8% of scratching events. When cows were provided with the
      mechanical brush, they decreased the frequency of scratching their heads,
      increased the frequency of scratching on their necks, backs, and tails, and
      tended to decrease the frequency of scratching their thighs. In conclusion, the
      results of this study show that the use of a mechanical brush makes it easier for
      cows to groom themselves, particularly in places that are hard to reach by the
      cow. This may help satisfy this natural behavior and keep them clean, as well as
      possibly reducing frustration or stress due to boredom when housed in freestall
      barns.

PMID- 17430924
TI  - Housekeeping gene expression in bovine liver is affected by physiological state,
      feed intake, and dietary treatment.
AB  - Selection of appropriate housekeeping genes (HKG) for normalization of
      quantitative PCR data for genes of interest is critical for interpretation of
      results. Ideally, copy number of the chosen HKG mRNA will not vary with
      experimental treatments or physiological state in the tissue studied, which
      improves accuracy in detecting changes in genes of interest. Because of the
      liver's dynamic role in metabolism, physiological state or dietary treatments
      could alter mRNA expression of commonly used HKG. Therefore, the objective of
      this study was to evaluate stability of mRNA expression for a number of candidate
      HKG in bovine liver across different physiological and dietary experimental
      conditions during the periparturient period. A publicly available program
      (geNorm) was used to evaluate expression stability of 8 HKG (beta-actin,
      glyceraldehyde 3-phosphate dehydrogenase, beta-glucuronidase, peptidylprolyl
      isomerase A, polyubiquitin, ribosomal protein S9, ribosomal protein L32, and 18S
      ribosomal RNA) in 91 liver RNA samples. Screened samples included liver from cows
      in 3 groups: 1) cows receiving a dietary supplement pre- and postpartum (n = 10);
      2) cows with clinical or subclinical ketosis (n = 7); and 3) cows consuming
      different amounts of energy prepartum (n = 74). In group 3, samples from d -65, 
      30, -14, 1, 14, 28, and 49 relative to parturition were included to enable
      characterization of HKG mRNA expression across different physiological states.
      Initial analyses indicated that mRNA for ribosomal protein S9 (RPS9) was one of
      the most stably expressed across different experiment types. To determine the
      best gene, 200 bootstrap replications of the original data set were performed to
      determine if the ranking of RPS9 was superior to the other 7 genes evaluated.
      Average ranks and estimated standard errors for the top 3 genes were 1.64 +/-
      0.06, 3.27 +/- 0.10, and 3.71 +/- 0.12 for RPS9, GAPDH, and beta-actin,
      respectively. Ribosomal protein S9 was ranked first 59% of the time and was never
      ranked lower than fifth. The lowest-ranked gene was polyubiquitin, ranked last
      46.5% of the time (average rank = 6.85 +/- 0.10). In this study, physiological
      state, amount of intake, or dietary treatment influenced the mRNA expression of
      commonly used HKG in bovine liver. Ideally, expression stability should be tested
      before collection of data in all experiments; however, we have shown that RPS9
      mRNA is stable across several physiological and diet-related experimental
      conditions for dairy cows, making it a good HKG in liver quantitative PCR
      experiments.

PMID- 17430925
TI  - Application of a new portable microscopic somatic cell counter with disposable
      plastic chip for milk analysis.
AB  - The somatic cell count (SCC) is one of the international standards for monitoring
      milk quality, and it is a useful indicator of mastitis. The current reference
      method for determining the SCC in raw milk is direct microscopic analysis, but
      this method requires well-trained staff to maintain its accuracy and
      reproducibility. To overcome these inconveniences, we developed a portable system
      (the C-reader system) that utilizes the capillary flow of a microfluidic chamber
      by surface modification of the hydrophilicity. The microfluidic technology of
      disposable microchips allows for low consumption of reagents, and a combination
      of ready-to-use reagents makes the daily work easier. The repeatability test of
      the C-reader using 10 composite bovine milk samples satisfied the recommended
      values for SCC equipment. In addition, an acceptable accuracy level of the
      natural logarithmic-transformed SCC [ln(SCC/1,000): +/- 0.059 to 0.112] was
      achieved using composite raw milk samples and various somatic cell standard
      solutions from the American Eastern Laboratory and the Korean National Veterinary
      Research and Quarantine Service. After testing 875 composite milk samples, the C
      reader showed a high correlation coefficient (R2 = 0.935 to 0.964) and a low mean
      difference value in log-transformed SCC (-0.088 to 0.004) compared with 3
      automatic commercialized somatic cell counters (Fossomatic 4000, Somacount 150,
      and Somascope). In conclusion, the C-reader system is a new, easy-to-use
      automatic on-farm method with acceptable repeatability and accuracy for measuring
      SCC in large dairies and smaller laboratories.

PMID- 17430926
TI  - Yield losses associated with clinical mastitis occurring in different weeks of
      lactation.
AB  - The effects of the first lactational incidence of clinical mastitis (CM) on milk,
      fat, and protein production were studied in the Swedish Red and Swedish Holstein
      breeds. The data consisted of 38,535 weekly production records from 1,192
      lactations (506 cows), sampled from 1987 to 2004 in one of the university's
      research herds. Daily yields were analyzed using a repeated-measures mixed model
      with an interaction between mastitis index and lactational stage, breed, parity,
      reproductive status, year-season of calving, and various indices for other
      disorders as independent variables. The indices were used to distinguish between
      cows with and without the studied diagnoses, as well as to indicate time (test
      day) in relation to day of diagnosis. Inclusion of the interaction made it
      possible to study the effects of CM occurring in different weeks of lactation.
      Primiparous and multiparous cows were analyzed separately, and the yields of
      nonmastitic cows were used as a reference for the production level in healthy
      cows. Lactational (305-d) yield losses were extrapolated from the daily
      estimates. High milk yield was predisposing to CM. Daily milk yield started to
      decline 2 to 4 wk before diagnosis. On the day of clinical onset, the milk yield
      of mastitic cows was reduced by 1 to 8 kg. After a case of CM, milk yield was
      suppressed throughout lactation. The magnitude of the yield losses was determined
      by the week of lactation at clinical onset. The greatest losses occurred when
      primiparous cows developed CM in wk 6, whereas multiparous cows experienced the
      greatest losses when diseased in wk 3. The 305-d milk, fat, and protein
      production in mastitic primiparous cows were reduced by 0 to 9, 0 to 8, and 0 to
      7%, respectively. The corresponding reductions in mastitic multiparous cows were
      0 to 11, 0 to 12, and 0 to 11%, respectively.

PMID- 17430927
TI  - Effects of environmental heat on conception rates in lactating dairy cows:
      critical periods of exposure.
AB  - Environmental heat can reduce conception rates (the proportion of services that
      result in pregnancy) in lactating dairy cows. The study objectives were to
      identify periods of exposure relative to the service date in which environmental
      heat is most closely associated with conception rates, and to assess whether the
      total time cows are exposed to high environmental heat within each 24-h period is
      more closely associated with conception rates than is the maximum environmental
      heat for each 24-h period. A retrospective observational study was conducted in
      25 predominantly Holstein-Friesian commercial dairy herds located in Australia.
      Associations between weather and conception rates were assessed using 16,878
      services performed over a 21-mo period. Services were classified as successful
      based on rectal palpation. Two measures of heat load were defined for each 24-h
      period: the maximum temperature-humidity index (THI) for the period, and the
      number of hours in the 24-h period when the THI was >72. Conception rates were
      reduced when cows were exposed to a high heat load from the day of service to 6 d
      after service, and in wk -1. Heat loads in wk -3 to -5 were also associated with
      reduced conception rates. Thus, management interventions to ameliorate the
      effects of heat load on conception rates should be implemented at least 5 wk
      before anticipated service and should continue until at least 1 wk after service.
      High autocorrelations existed between successive daily values in both measures,
      and associations between day of heat load relative to service day and conception
      rates differed substantially when ridge regression was used to account for this
      autocorrelation. This indicates that when assessing the effects of heat load on
      conception rates, the autocorrelation in heat load between days should be
      accounted for in analyses. The results suggest that either weekly averages or
      totals summarizing the daily heat load are adequate to describe heat load when
      assessing effects on conception rates in lactating dairy cows.

PMID- 17430928
TI  - Short communication: A positive relationship between the first ovulation
      postpartum and the increasing ratio of milk yield in the first part of lactation
      in dairy cows.
AB  - The aim of the present study was to examine the relationship between
      characteristics of the lactation curve, on the basis of daily milk yield, and
      ovulation within 3 wk postpartum as an indicator of early return to luteal
      activity in dairy cows. Lactation records from 46 lactating Holstein cows between
      calving and 305 d postpartum were studied. Milk samples were collected twice
      weekly between d 7 and 100 for later determination of progesterone
      concentrations. Occurrence of an early first ovulation was determined by an
      increase in milk progesterone by 3 wk after calving. Milk yield was recorded
      daily until 305 d postpartum, and average yield was calculated weekly. The
      lactation curve was characterized by 8 indices on the basis of the weekly average
      of milk yield as follows: a) first-week milk yield; b) peak milk yield; c) actual
      305-d milk yield; d) peak week; e) difference in milk yield between the first
      week and peak week; f) difference in milk yield between the peak week and last
      week (43rd week postpartum); g) ratio of increase in milk yield between wk 1 and
      the week of peak yield; and h) ratio of decline in milk yield between the week of
      peak yield and the last week. Indices g and h were calculated as linear. The
      number of cows having ovulated by 3 wk postpartum was 22 (47.8%). The resumption
      of ovarian cycles with normal luteal phases occurred earlier in ovular cows than
      in anovular cows (32.0 d vs. 57.1 d). Although total milk yield did not differ
      between ovular and anovular cows, the ratio of increase in milk yield from the
      first week to the peak week (index g) in ovular cows was smaller compared with
      that of anovular cows (1.71 vs. 2.54). In addition, the ratio of increase in milk
      yield from the first week to the third week postpartum was greater in anovular
      cows by 3 wk postpartum (ovular = 1.43 +/- 0.23 vs. anovular = 2.32 +/- 0.29). In
      conclusion, the present study demonstrates that a greater increasing ratio of
      milk yield during early lactation may delay resumption of ovarian cycles after
      parturition. Therefore, this study is the first to demonstrate statistically that
      a smaller increasing ratio of milk yield (index g) during early lactation may
      have a beneficial effect on the first ovulation by 3 wk postpartum.

PMID- 17430929
TI  - A probabilistic neural network model for lameness detection.
AB  - A 4-balance system for measuring the leg-load distribution of dairy cows during
      milking to detect lameness was developed. Leg weights of 73 cows were
      successfully recorded during almost 10,000 robotic milkings over a period of 5
      mo. Cows were scored weekly for locomotion, and lame cows were inspected
      clinically for hoof lesions. Unsuccessful measurements, caused by cows standing
      outside the balances, were removed from the data with a special algorithm, and
      the mean leg loads and number of kicks during milking were calculated. To develop
      an expert system to automatically detect lameness cases, a model was needed, and
      a classifying probabilistic neural network model was chosen for the task. The
      data were divided into 2 parts and 5,074 measurements from 37 cows were used to
      train a classifying probabilistic neural network model. The operation of the
      model was evaluated for its ability to detect lameness in the validating data
      set, which had 4,868 measurements from 36 cows. The model was able to classify
      96.2% of the measurements correctly as sound or lame cows, and 100% of the
      lameness cases in the validation data were identified. The number of measurements
      (equal to the number of milkings) causing false alarms was 1.1%. The model
      developed has the potential to be used as an on-farm decision aid and can be used
      in a real-time lameness monitoring system.

PMID- 17430930
TI  - Prepartum milking of heifers influences future production and health.
AB  - Transition heifers face multiple stressors during the periparturient period,
      including first exposure to milking, that may adversely impact dry matter intake
      (DMI), reduce milk production, compromise immune function, and increase
      susceptibility to disease. It was hypothesized that reducing the combined
      stressors experienced at calving would improve the periparturient performance,
      health, and well-being of heifers. The objective of this study was to determine
      the effect of initiating the milking procedure 3 wk before expected calving on
      production, DMI, body weight, energy balance, udder health, calving traits, and
      health status, as indicated by plasma acute phase protein concentrations. Twenty
      two primigravid heifers, blocked by expected calving date, were assigned randomly
      either to a prepartum milking (PM) group or control group. The PM heifers were
      milked twice daily beginning at 21 d before expected calving, and control heifers
      were not milked until after calving. All heifers had access to the same
      precalving and post-calving diets. Results indicated that PM heifers produced
      more milk during the first 2 wk after calving and had greater DMI as a percentage
      of body weight during the first month after calving than did control heifers,
      although energy balance was more negative for PM heifers. The PM heifers had
      reduced somatic cell counts through the first month after calving and lower
      average somatic cell scores during lactation despite having more quarters with
      mastitis infection at calving. The PM heifers had less udder edema at the third
      milking postcalving, and had reduced concentrations of haptoglobin in blood
      sooner than did control heifers. These results indicate that prepartum milking is
      an alternative management practice that has beneficial effects on the production,
      health, and well-being of first-lactation cows.

PMID- 17430931
TI  - Technical note: Estimation of milk fatty acid yield from milk fat data.
AB  - Most publications reporting milk fatty acid (FA) yields estimate these yields
      from milk fat yields and a coefficient estimating the proportion of FA in milk
      fat. The most widely used coefficient is, in fact, the proportion of fatty acyl
      radicals (i.e., FA from which the OH group has been removed) in milk
      triglycerides, equivalent to a mean proportion of 88% FA in milk fat. From a
      metabolic point of view, because the digestive flows and mammary FA uptake
      consist of nonesterified FA, it is more logical to estimate the FA proportion
      rather than the fatty acyl proportion in milk fat. From 588 milk FA profiles, we
      estimated a mean proportion of 94.4% FA in milk triglycerides. Moreover, when the
      other milk lipid classes (phospholipids, diglycerides, etc.) were taken into
      account, the proportion of FA in milk total lipids was estimated at 93.3%, almost
      independently of the milk FA profile. The use of this coefficient to estimate the
      secretion of milk FA on the basis of milk fat yield data is more physiologically
      relevant for milk FA secretion studies.

PMID- 17430932
TI  - Short communication: Rate of propionate infusion within meals does not influence
      feeding behavior.
AB  - Propionate has been shown to depress the feed intake of ruminants, but whether
      the rate of propionate infusion influences this response is unknown. To test this
      possibility, the rate of propionate infused within meals was altered while the
      total amount of propionate infused was held constant. Eight multiparous Holstein
      cows (51 +/- 19 d in milk, 44.0 +/- 4.8 kg/d of milk; mean +/- SD) were randomly
      assigned to the treatment sequence in a crossover experiment with a 10-d diet
      adaptation period, 24-h treatment periods, and 3 d between treatments. Treatments
      were intraruminal infusion of 1.26 mol of Na propionate (2.33 +/- 0.06 L, 0.54 M,
      pH 6.0) over the course of either 5 min (fast) or 15 min (slow) at each
      spontaneous meal. The experimental diet included high-moisture corn and was
      formulated for 27% neutral detergent fiber, 36% starch, and 17.5% crude protein.
      Feeding behavior was monitored by a computerized data acquisition system that
      triggered infusion pumps at the initiation of meals, and consecutive infusions
      began at least 15 min apart under both treatment protocols. Feeding behavior data
      were analyzed to quantify the number, size, length, and time between all meals.
      Compared with pretreatment intake, propionate infusions depressed feed intake by
      20 and 23%, respectively, for the slow and fast treatments. However, the rate of
      propionate infusion did not significantly alter dry matter intake, meals/day,
      meal size, meal length, or intermeal interval. We found no evidence that the rate
      of infusion, within the range of typical meal lengths, determines the extent of
      hypophagia from propionate.

PMID- 17430933
TI  - The effect of Lactobacillus buchneri 40788 on the fermentation and aerobic
      stability of ground and whole high-moisture corn.
AB  - Experiments were conducted to evaluate the effects of inoculating high-moisture
      corn (HMC) with Lactobacillus buchneri 40788 on silage fermentation and aerobic
      stability. In the first experiment, HMC (73% DM) was ground and treated with
      nothing, L. buchneri 40788 to achieve 6.6 x 10(5) cfu/g of HMC (LB), a mixture of
      enzymes (ENZ), LB + ENZ, or 0.1% (wet weight basis) of a liquid mold inhibitor
      and was ensiled in 20-L bucket silos for 90 d. Treatments with LB and LB + ENZ
      increased the concentrations of acetic acid and improved the aerobic stability of
      ground HMC relative to other treatments. Treatment ENZ had no effect on the
      chemical composition or aerobic stability of ground HMC. The only effect of the
      liquid mold inhibitor relative to untreated HMC was that it increased the
      concentration of propionic acid, but this did not improve its aerobic stability.
      In a second experiment, HMC (75% DM) was harvested as the intact, whole grain and
      treated with nothing, L. buchneri 40788 to achieve 4 x 10(5) cfu/g of HMC, L.
      buchneri 40788 to achieve 6 x 10(5) cfu/g of HMC, or L. buchneri 40788 to achieve
      8 x 10(5) cfu/g of HMC and ensiled for 120 d. Treatments with L. buchneri 40788
      resulted in whole HMC with lower concentrations of water-soluble carbohydrates;
      higher concentrations of lactic, acetic, and propionic acids; and greater numbers
      of lactic acid bacteria but fewer molds when compared with untreated corn. As a
      group, inoculated silages were more aerobically stable than untreated silage, but
      increasing levels of application did not further improve the response. These
      experiments showed that addition of L. buchneri 40788, but not addition of an
      enzyme mixture or a liquid mold inhibitor, improved the aerobic stability of
      ground and whole HMC harvested between 73 and 75% DM.

PMID- 17430934
TI  - Assessment of the effects of cinnamon leaf oil on rumen microbial fermentation
      using two continuous culture systems.
AB  - Two continuous culture (CC) systems, the rumen simulation technique (Rusitec) and
      a dual-flow (DF) fermenter, were used to evaluate effects of the essential oil
      from cinnamon leaf (CIN) on rumen microbial fermentation. Incubations (d 1
      through 8 for adaptation and d 9 through 16 for sampling) were conducted
      concurrently in the 2 systems, with CIN added at 0 (control) and 500 mg/L of
      rumen fluid culture. Eight Rusitec (920 mL; dilution rate = 2.9%/h) and 6 DF
      (1,300 mL; dilution rate = 6.3%/h) fermenters were randomly assigned to
      treatment. Inoculum was prepared from 4 ruminally cannulated lactating Holstein
      cows fed a total mixed ration consisting of 51% forage and 49% concentrate (dry
      matter basis). Ruminal pH, total volatile fatty acid (VFA) concentration, and
      diet digestibility were reduced by CIN addition in the Rusitec but were not
      affected by CIN administration in the DF. The addition of CIN in the Rusitec
      decreased apparent N disappearance, NH3-N concentration, and molar proportions of
      branched-chain VFA. In contrast, in the DF no effect of CIN was observed on
      apparent N degradation, NH3-N concentration, and molar proportion of branched
      chain VFA. In the Rusitec, the molar proportion of acetate was similar between
      treatments on d 9 and 13, but was lower from d 10 to 12 and higher on d 14 to 16
      with CIN than with control (interaction of treatment x sampling day). The molar
      proportion of acetate remained unaffected by CIN addition in the DF. In both CC
      systems, the molar proportion of propionate was decreased whereas that of
      butyrate was increased by CIN addition. In the DF, CIN decreased microbial N flow
      and efficiency of microbial protein synthesis. Protozoa numbers were lower with
      CIN than with control in both CC fermenters. In the Rusitec, CIN increased 15N
      enrichment in total bacterial fractions, but no effect was observed on the
      production of microbial N. This study showed that CIN exhibited antimicrobial
      activity in both CC systems, but the effects were more pronounced in the Rusitec
      than in the DF system. These differences are likely a reflection of the higher
      dilution rate in the DF resulting in a lower effective concentration of CIN than
      in Rusitec. Based on these changes in rumen microbial fermentation,
      supplementation of CIN at the concentration evaluated in this study may not be
      nutritionally beneficial to ruminants.

PMID- 17430935
TI  - Performance and ruminal fermentation of dairy cows fed whole cottonseed with
      elevated concentrations of free fatty acids in the oil.
AB  - Twenty-four lactating Holstein cows were used in an 8-wk completely randomized
      design trial to examine the effects of feeding whole cottonseed (WCS) with
      elevated concentrations of free fatty acids (FFA) in the oil on intake and
      performance. Treatments included WCS with normal concentrations of FFA (6.8%,
      control) and 2 sources of WCS with elevated FFA [HFFA1 (24.1%) or HFFA2 (22.3%)].
      The 2 sources of WCS with elevated FFA differed in that HFFA2 were discolored
      from being initially stored with excess moisture, which led to heating and
      deterioration during storage, whereas HFFA1 were normal in appearance and the
      increase in FFA occurred without heating and visible damage to the WCS. Nutrient
      concentrations were similar among WCS treatments, which provided 14% of the total
      dietary dry matter. Dry matter intake tended to be higher for cows fed HFFA2
      compared with control and HFFA1. Yield of milk and components was similar among
      treatments, but milk fat percentage was lower for HFFA1 and HFFA2 compared with
      control. In a concurrent 3 x 3 Latin square trial with 6 ruminally cannulated
      Holstein cows, molar proportions of isobutyrate were higher for HFFA2 than
      control and HFFA1, but no differences were observed in acetate or propionate.
      Results of these trials indicate that feeding WCS with high concentrations of FFA
      decreases milk fat percentage but does not alter dry matter intake, milk yield,
      or concentrations of other components. The minor changes in ruminal fermentation
      that were observed do not account for the decrease in milk fat percentage.

PMID- 17430936
TI  - Variations in carotenoids, vitamins A and E, and color in cow's plasma and milk
      during late pregnancy and the first three months of lactation.
AB  - The main aim of this work was to assess the effect of lactation period on the
      secretion of carotenoids in cow's milk. Our objective was to determine the
      variations in carotenoids in the plasma and milk of dairy cows from drying off to
      wk 12 of lactation, and to specify whether these variations depend on body stores
      of these micronutrients at calving. We also investigated the relationship between
      beta-carotene (BC) and color in plasma and milk to evaluate the methods based on
      direct or indirect characterization of these micronutrients for traceability of
      feeding management. The experiment was carried out on 18 dairy cows, which were
      dried off 8 wk before their expected date of parturition. They were then divided
      into 2 homogeneous groups and fed diets contrasting in carotenoid content, high
      (grass silage) vs. low (corn silage), from wk -7 until parturition. From
      parturition through wk 12 of lactation, both groups received a grass silage-based
      diet. Variations in concentrations of carotenoids and the color index (CI) in
      plasma and milk were monitored from drying off to wk 12 of lactation. Other
      components of nutritional interest (i.e., vitamins A and E) were also measured.
      Lutein, all-trans BC and cis-13 BC were the carotenoids found in plasma and milk.
      Plasma concentrations of carotenoids, vitamin A, and vitamin E decreased
      throughout the dry period and in the first week of lactation, then increased
      through the first 3 mo of lactation, parallel to grass silage intake. For both
      groups, carotenoid and vitamin concentrations in milk drastically decreased
      during the first week of lactation, then did not vary significantly throughout
      the remainder to the experiment (wk 12). Plasma concentrations of carotenoids and
      vitamins were higher in the high-carotenoid group than in the low-carotenoid
      group during the dry period. Those differences were also observed in colostrum
      and disappeared in both plasma and milk during the first 10 d of the lactation
      period. This work allowed us to conclude that, unlike in plasma, variations in
      carotenoids, vitamin A, and vitamin E in milk were only slight in early
      lactation. In both plasma and milk, the concentrations were only transitorily
      affected by the nature of forage fed during the dry period, showing that they
      depended mainly on the dietary supply, even during the lipid mobilization period.
      The relationship between concentrations of BC and the CI was linear in plasma (R2
      = 0.51) and milk (R2 = 0.37) and reached a plateau in the milk + colostrum data
      set (R2 = 0.77). The changes in CI during the first 3 mo of lactation were not
      negligible compared with variations related to the nature of forage reported in
      previous studies. This implies that methods being developed for the traceability
      of feeding management of dairy cows based on direct or indirect characterization
      of these micronutrients in milk, plasma, or both will need to account for changes
      in relation to lactation stage, which requires further investigation.

PMID- 17430937
TI  - Short communication: Addition of milk replacer to colostrum whey: effect on
      immunoglobulin G passive transfer in Majorera kids.
AB  - Forty-two Majorera kids (21 males and 21 females) were assigned to 3 groups, a
      colostrum group (C), a colostrum whey group (CW), and a colostrum whey plus milk
      replacer group (CWMR). All kids were fed twice on the first day and received 4 g
      of IgG/kg of body weight. No differences were found in serum IgG among the
      different treatments. Kid serum IgG concentrations on d 2 were 14.57, 17.25, and
      13.32 mg/mL in the C, CW, and CWMR group, respectively. Labor time per animal was
      higher in the C and CW treatments than in the CWMR group (24.2 +/- 2.3, 20.9 +/-
      3.4, and 16.1 +/- 1.5 min, respectively). This new management system may decrease
      labor costs during the colostrum feeding period.

PMID- 17430938
TI  - Prevention of clinical mastitis with barium selenate in dairy goats from a
      selenium-deficient area.
AB  - Mastitis is one of the most negative factors involved in the economy of dairy
      goat farms. The effect of selenium on mammary gland resistance to infectious
      diseases has been demonstrated. This work evaluates the efficacy of a slow
      release Se salt (barium selenate) to reduce the incidence of clinical mastitis in
      goats reared on Se-deficient areas. Six hundred milking goats of the Malaguena
      breed, from 4 commercial dairy farms located in a Se-deficient area, were
      randomly allotted to 2 groups: treated group (given a subcutaneous injection of
      barium selenate at a dose of 1 mg of Se/kg of body weight 15 d before mating) and
      control group (no supplement). During the lactation the does were monitored to
      assess the occurrence of clinical mastitis by physical examination, California
      Mastitis Test performance, and microbiological study. The Se content of the
      ration consumed previously by the animals did not meet the requirements for dairy
      goats. The Se injection significantly increased glutathione peroxidase activity
      in the treated group and had evident beneficial effects in the subsequent
      lactation. The somatic cell count and the incidence of clinical mastitis were
      significantly lower in the treated group than in the control group. However, no
      significant differences were found for milk composition. Thus, in Se-deficient
      areas, the supplementation with Se of any source in programs for prevention of
      clinical mastitis and improvement of milk quality is strongly recommended.

PMID- 17430939
TI  - Effects of chop length of alfalfa and corn silage on milk production and rumen
      fermentation of dairy cows.
AB  - Effects of chop length (shorter = 10 mm or longer = 19 mm) of alfalfa silage and
      corn silage were determined in 16 midlactation Holstein cows using a 4 x 4 Latin
      square design with a 2 x 2 arrangement of treatments. Experimental periods were
      21 d long and consisted of 14 d of adaptation and 7 d of sampling. Cows received
      total mixed ration containing (dry matter basis) 44.0% barley grain-based energy
      supplement, 12.6% protein supplement, and 21.7% longer chop or shorter chop
      alfalfa silage and 21.7% longer chop or shorter chop corn silage. Reducing the
      chop length of alfalfa silage and corn silage reduced the average geometric
      particle length from 14.4 to 11.0 mm and from 14.2 to 10.4 mm, respectively.
      Reducing the chop length of both silages reduced the proportion of the diets
      retained by the 8- and 19-mm screen of the Penn State Particle Separator from
      55.0 to 46.0% of dry matter. Reducing the alfalfa chop length increased total
      rumen volatile fatty acids at 4 to 5 h after feeding but did not affect rumen pH
      at 4 to 5 h after feeding, feed intake, and milk production. Reducing the corn
      silage chop length increased dry matter intake from 22.3 to 23.2 kg/d, increased
      rumen pH at 4 to 5 h after feeding from 6.12 to 6.20, but did not alter rumen
      volatile fatty acids at 4 to 5 h after feeding or milk production. Daily milk
      yield, milk fat percentage, and milk protein percentage averaged 38.2 kg/d,
      2.62%, and 3.29%, respectively, across all diets. The low milk fat percentages
      suggest that all diets induced subacute ruminal acidosis (SARA), whereas the
      rumen pH did not indicate SARA. This discrepancy could be due to a difference in
      the time of rumen pH measurement and the time of the lowest rumen pH. Hence, the
      pH data need to be interpreted with caution. Diets could have induced SARA,
      because for all experimental diets the content of forage neutral detergent fiber
      was lower than recommended for barley grain-based diets.

PMID- 17430940
TI  - Effect of L-carnitine infusion and feed restriction on carnitine status in
      lactating Holstein cows.
AB  - Previously we determined that abomasal infusion of L-carnitine increased in vitro
      hepatic fatty acid oxidation, decreased liver lipid accumulation, and supported
      higher fat-corrected milk yield in feed-restricted lactating cows. The objectives
      of this study were to examine the effects of supplemental L-carnitine and amount
      of feed intake on free carnitine and carnitine ester concentrations in liver,
      muscle, milk, and plasma of lactating dairy cows. Eight lactating Holstein cows
      (132 +/- 36 d in milk) were used in a replicated 4 x 4 Latin square design with
      14-d periods to test factorial combinations of water or L-carnitine infusion (20
      g/d; d 5 to 14) and ad libitum or restricted (50% of previous 5-d intake; d 10 to
      14) dry matter intake. Plasma was obtained 3 times daily on d 4, 8, and 12; milk
      samples were collected on d 8, 9, 13, and 14. Liver and muscle were biopsied on d
      14 of each period. Free carnitine, short-chain acylcarnitine, and long-chain
      acylcarnitine concentrations were determined using a radioenzymatic assay coupled
      with ion exchange chromatography. Abomasal L-carnitine infusion increased total
      carnitine in plasma on d 8 and d 12. All liver carnitine fractions were increased
      by carnitine infusion. Feed restriction elevated concentrations of free
      carnitine, long-chain acylcarnitine, and total carnitine in liver tissue from
      carnitine-infused cows but not in those infused with water. In muscle, acid
      soluble carnitine, long-chain acylcarnitine, and total carnitine concentrations
      were increased by carnitine infusion and feed restriction without significant
      interaction. Feed restriction increased free carnitine concentrations in muscle
      from water-infused cows but not in carnitine-infused cows. Carnitine infusion
      increased the concentration of each milk carnitine fraction as well as milk
      carnitine output on d 8 to 9. On d 13 to 14, all carnitine fractions except short
      chain acylcarnitine were increased in milk from water-infused, feed-restricted
      cows, whereas all fractions were increased in carnitine-infused, feed-restricted
      cows. Carnitine infusion increased total carnitine in plasma, liver, muscle, and
      milk during feed restriction, whereas feed restriction alone increased carnitine
      concentrations in muscle and milk but not in liver. Liver carnitine
      concentrations might limit hepatic fatty acid oxidation capacity in dairy cows
      during the periparturient period; therefore, supplemental L-carnitine might
      decrease liver lipid accumulation in periparturient cows.

PMID- 17430941
TI  - Estimation of the proportion of feed protein digested in the small intestine of
      cattle consuming wet corn gluten feed.
AB  - The objectives of this study were to expand the database and determine the
      intestinal digestibility of rumen undegradable protein (dRUP) of common dairy
      feeds and to determine the effects of feeding 37.9% wet corn gluten feed on these
      estimates. Two ruminally and duodenally fistulated steers were assigned randomly
      to a crossover design with 4-wk periods. The mobile bag technique was used to
      determine rumen undegradable protein (RUP), dRUP, total tract digestible protein,
      and total tract digestible dry matter of alfalfa hay, brome hay, alfalfa haylage,
      corn silage, whole cottonseed, soybean meal, soyhulls, ground corn,
      nonenzymatically browned soybean meal, and dried distillers grains. There was no
      consistent effect of diet on RUP, dRUP, total tract digestible protein, and total
      tract digestible dry matter. The RUP (% of crude protein) ranged from 5.97% for
      alfalfa haylage to 75.6% for nonenzymatically browned soybean meal. The dRUP
      ranged from 15.3% for alfalfa haylage to 96.5% for nonenzymatically browned
      soybean meal. The dRUP for alfalfa hay (33.9%), brome hay (39.1%), alfalfa
      haylage (15.5%), and corn silage (19.9%) were lower than National Research
      Council reported values. The higher dRUP of the nonenzymatically browned soybean
      meal is reflective of more total protein reaching the small intestine. The large
      range in dRUP was not reflected in total tract digestible protein (% of crude
      protein), with corn silage being the lowest at 85.2% and nonenzymatically browned
      soybean meal the highest at 97.9%. In this study, diet had little effect on
      intestinal digestibility of protein or dry matter.

PMID- 17430942
TI  - Short communication: Feed selection by dairy cows fed individually in a tie-stall
      or as a group in a free-stall barn.
AB  - The objectives of the present study were to compare feed selection in tie- vs.
      free-stall barns and also to verify possible correlations between feed selection
      and milk composition. Forty multiparous and 20 primiparous lactating Holstein
      cows were utilized in a crossover design with 21-d periods. Cows were randomly
      divided into 2 groups; group 1 was housed in a free-stall barn during period 1
      and a tie-stall barn during period 2, and vice versa for group 2. In the free
      stall barn, 18 extra cows were also present. Animals were fed the same diet once
      daily in the free-stall barn at 1100 h and twice daily at 1100 and 1500 h in the
      tie-stall barn to obtain approximately 10% daily refusals in both facilities.
      Group feed selection in the free-stall barn was measured and compared with the
      group feed selection in the tie-stall barn, obtained by summing individual feed
      offered and refused. Feed selection was analyzed including treatment and period
      in the model. Sequence effect and true error were combined into a single degree
      of freedom error term. Intake of the longest particles expressed as a percentage
      of the predicted intake was 73.2% in a tie-stall barn and 63.3% in a free-stall
      barn. There were no significant correlations between individual feed selection
      measured in the tie-stall barn and milk composition. Feed selection estimates
      made with individually fed cows are likely to underestimate average feed
      selection in a free-stall barn.

PMID- 17430943
TI  - Effect of roughage source and roughage to concentrate ratio on animal performance
      and rumen development in veal calves.
AB  - Sixty-four male Holstein-Friesian x Dutch Friesian veal calves (46 +/- 3.0 kg)
      were used to evaluate the effect of the inclusion of different levels and sources
      of dietary roughage on animal performance and rumen development. Treatments
      consisted of 1) C100 = concentrate only; 2) C70-S30 = concentrate (70%) with
      straw (30%), 3) C70-G30 = concentrate (70%) with dried grass (30%), 4) C70-G15
      S15 = concentrate (70%) with dried grass (15%) and straw (15%), 5) C70-CS30 =
      concentrate (70%) with corn silage (30%), 6) C40-CS60 = concentrate (40%) with
      corn silage (60%), 7) C70-CS30-AL = concentrate (70%) with corn silage (30%) ad
      libitum, 8) C70-G15-S15-AL = concentrate (70%) with dried grass (15%) and straw
      (15%) ad libitum. All dietary treatments were provided in addition to a
      commercial milk replacer. Concentrate was provided as pellets and roughage was
      chopped. The dietary treatments 1 to 6 were supplied restrictedly to a maximum of
      750 g of dry matter (DM) per day, whereas treatments 7 and 8 were offered ad
      libitum in combination with a reduced amount of milk replacer. Calves were
      euthanized after 10 wk. Straw supplementation (C70-S30 vs. C70-G30 and C70-CS30)
      reduced DM intake, and ad libitum supply of concentrate and roughage increased DM
      intake. Roughage addition did not affect growth performance. Rumen fermentation
      was characterized by low pH and high total volatile fatty acids and reducing
      sugar concentrations. Calves fed ad libitum showed lower ruminal lactate
      concentrations than calves fed restrictedly. Ammonia concentrations were highest
      in calves fed C-100 and lowest in calves fed ad libitum. The recovery of CoEDTA
      (added to milk replacer) varied between 20.5 and 34.9%, indicating that
      significant amounts of milk entered the rumen. Roughage addition decreased the
      incidence of plaque formation (rumen mucosa containing focal or multifocal
      patches with coalescing and adhering papillae covered by a sticky mass of feed,
      hair and cell debris) and the incidence of calves with poorly developed rumen
      mucosa. However, morphometric parameters of the rumen wall were hardly influenced
      by the type and level of roughage. Ruminal polysaccharide-degrading enzyme
      activities reflected the adaptation of the microorganisms to the dietary
      concentrate and roughage source. Results indicated that in veal calves, the
      addition of roughage to concentrate diets did not affect growth performance and
      positively influenced the macroscopic appearance of the rumen wall.

PMID- 17430944
TI  - Effect of a soy protein-based diet on ribonucleic acid metabolism in the small
      intestinal mucosa of goat kids.
AB  - This study was designed to investigate the effect of soy protein inclusion in
      milk replacer diets for goat kids on protein, RNA, and DNA contents in small
      intestinal mucosa, on the importance of RNA biosynthesis from dietary RNA
      precursors for mucosal RNA synthesis, and on the activities of enzymes involved
      in nucleotide degradation in small intestinal mucosa. Diets were based on cow's
      milk. In the control group, 35% of the milk protein was replaced by casein (CN)
      protein, and in the soy group (SPAA), the same amount of milk protein was
      replaced by soy protein supplemented with essential AA known to be at lower
      concentrations in soy than in CN (Thr, Val, Ile, Leu, His, Lys, Met). Diets were
      isonitrogenous and isoenergetic. At 47 d of age, goats were harvested and samples
      of proximal, middle, and distal jejunal mucosa were collected 5 h after feeding
      15N-labeled RNA from yeast (13 mg/kg of body weight). Growth and feed conversion
      did not differ between the control and SPAA kids. Mucosal protein concentrations
      were lower in the SPAA than the control kids. Concentrations of RNA and DNA did
      not differ between feeding groups, but in all kids mucosal RNA concentrations
      were higher in proximal than in middle and distal jejunum. Protein:RNA ratios
      were higher in the control than the SPAA kids and were lowest in proximal
      jejunum. Activities of alkaline phosphatase in enterocytes were higher in
      proximal than in middle and distal jejunum. Activities of mucosal xanthine
      oxidase were highest in distal jejunum and were higher in the SPAA than the
      control kids, especially in the middle and distal sites. The 15N-enrichment of
      mucosal RNA was higher in the control than the SPAA kids, especially in distal
      jejunum, and was lowest in distal jejunum. In contrast, 15N-enrichment of urea in
      plasma tended to be higher and Gly concentration in plasma was lower in the SPAA
      than the control kids. Data indicate that protein content and the protein:RNA
      ratio were lower in jejunal mucosa of goat kids fed milk replacer with partial
      replacement of CN protein by soy protein. These findings were accompanied by a
      lower level of reutilization of preformed dietary RNA precursors for RNA
      biosynthesis in jejunal mucosa and a higher activity of xanthine oxidase. Thus,
      feeding soy protein instead of CN protein reduced the incorporation of preformed
      dietary RNA precursors for RNA biosynthesis in the mucosa and activated key
      enzymes involved in nucleic acid breakdown.

PMID- 17430945
TI  - Supplemental choline for prevention and alleviation of fatty liver in dairy
      cattle.
AB  - Two experiments were conducted to evaluate if supplementing rumen-protected
      choline (RPC; Reashure, Balchem Encapsulates, Slate Hill, NY) could prevent or
      alleviate fatty liver in dairy cattle. The first experiment evaluated the effect
      of supplementing RPC on hepatic triacylglycerol (TAG) accumulation during fatty
      liver induction. Twenty-four dry cows between 45 to 60 d prepartum were paired by
      body weight (BW) and body condition score (BCS) and randomly assigned to control
      or supplementation with 15 g of choline as RPC/d. From d 0 to 6, before treatment
      application, all cows were fed 1.4 kg/d of concentrate and forage ad libitum.
      Samples of blood and liver, obtained during the pretreatment period, were used
      for covariate adjustment of blood metabolites and liver composition data. During
      fatty liver induction (d 7 to 17), cows were fed 1.4 kg/d of concentrate with or
      without supplementation with RPC, and forage intake was restricted, so cows
      consumed 30% of the total energy requirements for pregnancy and maintenance.
      Supplementation with RPC during fatty liver induction did not affect plasma
      glucose and plasma beta-hydroxybutyrate (BHBA) concentration but did decrease
      plasma nonesterified fatty acid (NEFA; 703 vs. 562 microEq/L, SE = 40) and liver
      TAG accumulation (16.7 vs. 9.3 microg/microg of DNA, SE = 2.0). In the second
      experiment, we evaluated the effect of supplementing RPC on the clearance of
      liver TAG when cows were fed ad libitum after the induction of fatty liver by
      feed restriction. Twenty-eight cows between 45 and 60 d prepartum were paired
      according to BCS and BW and assigned to treatments. Fatty liver was induced by
      feeding 1.4 kg/d of concentrate (without RPC) and restricting forage intake, so
      cows consumed 30% of maintenance and pregnancy energy requirements for 10 d. From
      d 11 to 16, after feed restriction, cows were fed forage ad libitum and 1.4 kg/d
      of concentrate with or without RPC. Treatments were not applied during fatty
      liver induction; however, following feed restriction, liver for cows assigned to
      control and RPC treatments contained 6.8 and 12.7 microg of TAG/microg of DNA,
      respectively. Measurements obtained before treatment served as covariates for
      statistical analysis. During the depletion phase, plasma glucose, BHBA, and NEFA
      were not affected by treatment. Liver TAG, expressed as covariate adjusted means,
      was 6.0 and 4.9 microg/microg of DNA (SE = 0.4) on d 13, and 5.0 and 1.5
      microg/microg of DNA (SE = 0.9) on d 16 for control and RPC, respectively. Rumen
      protected choline can prevent and possibly alleviate fatty liver induced by feed
      restriction.

PMID- 17430946
TI  - Selection responses for disease resistance in two selection experiments with
      Norwegian red cows.
AB  - Genetic trends for clinical mastitis (CM), ketosis (KET), retained placenta (RP),
      and 305-d protein yield (PY305) were calculated for 2 Norwegian dairy cattle
      selection experiments. The first experiment, accomplished from 1978 to 1989,
      included groups selected for high (HMP) and low milk production (LMP). The second
      experiment started in 1989 and included selection for high protein yield (HPY)
      and low mastitis frequency (LCM). In both experiments proven sires from the
      active breeding program of Norwegian Red were used as sires. To take into account
      that selection of sires was external to the experiment, all available data from
      the Norwegian Red population, including disease records for 2.7 million first
      lactation cows, were analyzed with a multivariate animal model. Estimated
      breeding values for cows in the experiments were extracted from this analysis to
      calculate genetic trends in the selection groups. Genetic trends for PY305 were,
      as expected, positive for the HMP and HPY groups, and negative for LMP and LCM.
      The HMP group showed increasing genetic trends for all 3 diseases, arguably a
      correlated response after selection for increased milk production, whereas the
      LCM group showed decreasing genetic trends for CM, KET, and RP. The genetic
      trends for KET and RP in the LCM group are most likely correlated responses after
      selection against CM. After 5 cow-generations the genetic difference between HPY
      and LCM was 10 percentage units CM, 1.5 percentage units KET, and 0.5 percentage
      units RP.

PMID- 17430947
TI  - Pattern of expression of the uterine milk protein gene and its association with
      productive life in dairy cattle.
AB  - The uterine milk proteins (UTMP) are the major proteins secreted by the
      endometrium, primarily under the control of progesterone. Specific functions of
      UTMP are poorly understood, but may include protease inhibition, nutrition of the
      conceptus, growth control, and suppression of the maternal immune system. The
      uterine milk protein gene (UTMP) was chosen for this study because of its
      possible roles in health traits and results of previous studies on the
      association of the UTMP region with milk production and productive life in dairy
      cattle. Expression of UTMP was examined in 198 bovine tissues obtained from 10
      fetuses and 17 cows. Transcripts of UTMP were found in all cotyledon tissues
      examined and to a lesser extent in ovary, pituitary, and spleen tissues obtained
      from fetuses. The UTMP gene was predominantly expressed in endometrium (17/17),
      ovary (15/16), and caruncle (12/12) tissues obtained from cows. The predominant
      expression of UTMP in reproductive tissues is consistent with an important role
      of this gene in reproductive success. To investigate the association between UTMP
      and production traits in cattle, we identified 2 synonymous single nucleotide
      polymorphisms (SNP) at positions 1179 (A/G) and 1296 (A/G) using the pooled DNA
      sequencing approach. The DNA was extracted from 28 Holstein sires and their 1,362
      sons obtained from the Cooperative Dairy DNA Repository and from 913 cows from
      the University of Wisconsin resource population. Single nucleotide polymorphism
      1296 was associated with a significant increase in productive life in both
      populations. This finding is similar to results previously obtained for the
      protease inhibitor gene, which is near UTMP and was also found to be associated
      with productive life in dairy cattle. Differential allelic expression of UTMP was
      observed in reproductive tissues obtained from 9 heterozygous individuals. The
      differential allelic expression observed in this study is consistent with other
      studies showing a correlation between allelic variation in gene expression and
      phenotypic variability.

PMID- 17430948
TI  - Genetic evaluations for mixed-breed populations.
AB  - An all-breed animal model was developed for routine genetic evaluations of US
      dairy cattle. Data sets from individual breeds were combined, and records from
      crossbred cows were included. About 1% of recent cows were first-generation
      crossbreds. The numbers of cows with records since 1960 ranged from 10 to 22
      million for the 6 traits analyzed, which were milk, fat, protein, somatic cell
      score, productive life, and daughter pregnancy rate. Programs were modified to
      account for general heterosis, to group unknown parents separately by breed, to
      adjust variances separately by breed, and to adjust data to a 36-mo age
      equivalent instead of a mature equivalent. Convergence rate of the all-breed
      model was similar to that of the previous within-breed animal model. Estimated
      breed differences were similar to those obtained previously from phenotypic breed
      means or from studies of crossbred cows and their herd-mates. Genetic evaluations
      from the all-breed and within-breed systems had high correlations: >0.99 for
      recent Holsteins and slightly <0.99 for other breeds. Predicted transmitting
      abilities will be converted back to the within-breed bases for purebred animals
      and to the breed of sire base for crossbred animals so that most purebred
      breeders will not be affected by the change to a multibreed model. Evaluations of
      crossbred animals from the multibreed model can include accurate information for
      both parents. Reliabilities also increase for purebred relatives because of the
      additional crossbred records and in mixed breed herds because cows of other
      breeds are additional contemporaries. Another benefit of the multibreed model is
      that breed differences are routinely estimated and updated. More research and
      education may be needed on using the new evaluations in the design of breeding
      programs. Implementation is expected in May 2007.

PMID- 17430949
TI  - Selection for profit in cattle: I. Economic weights for purebred dairy cattle in
      the Czech Republic.
AB  - A bioeconomic model for dairy cattle production was used to estimate economic
      values of 18 traits for dairy sires in purebred Holstein and Czech Fleckvieh
      populations. Economic values were defined as partial derivatives of the profit
      function with respect to each trait in a closed production system with dairy cow
      herds and integrated fattening of bulls. All revenues and costs associated with
      cows calving in the herds within one year and with their progeny were discounted
      at 5% per annum back to the date of calving. Calculations were carried out for
      the situation in the Czech Republic in 2005 (scenario 1: market quotas for milk
      yield and fat percentage) and for the expected situation in 2015 (scenario 2:
      free market). The relative economic importance of each trait was expressed as a
      ratio of the standardized economic value of that trait (its marginal economic
      value multiplied by its genetic standard deviation) to the standardized economic
      value of 305-d milk yield, with average fat and protein percentages. In addition
      to milk yield, somatic cell score was the second most important trait, achieving
      32% to 43% of the value for milk yield in both scenarios. The relative importance
      of milk components differed notably between scenarios. The relative importance
      was approximately zero for protein and from -14 to -23% for fat percentage in
      scenario 1, but changed to 38% for protein and 27 to 31% for fat percentage in
      scenario 2. In both scenarios and for both breeds, the relative economic values
      for somatic cell score and length of productive life of cows were similar to
      those for fat and protein percentages in scenario 2. The smallest relative
      economic values (less than 4% of the relative importance of milk yield) were for
      birth weight, conception rate of heifers, and carcass traits. In conclusion,
      relative emphasis among traits in the breeding objective for Czech dairy cattle
      should be reassessed according to the expected situation after shifting to a free
      market economy in 2015.

PMID- 17430950
TI  - Selection for profit in cattle: II. Economic weights for dairy and beef sires in
      crossbreeding systems.
AB  - The relative economic importance (economic weights) of 18 traits was determined
      for Holstein and Charolais sires used in a dairy production system applying cross
      breeding with beef sires and in a cow-calf pasture cross-breeding system with
      integrated fattening of surplus animals. A bioeconomic model containing a profit
      function was used for the calculations in both systems. Discounted expressions
      for direct and maternal components of the traits during an investment period of
      25 yr were calculated using the gene-flow technique. The relative economic
      weights for some traits or trait components of the dairy sires differed
      substantially between the purebred and crossbred dairy systems. There were also
      meaningful differences among the relative economic weights of traits for beef
      sires, depending on whether these bulls were used for terminal crossing with F1
      females in the cow-calf pasture system (back-crossing), for crossing in dairy
      herds producing slaughter animals, or for crossing in dairy herds producing F1
      females for the cow-calf pasture system. We therefore recommend construction of
      specific sets of subindices for dairy and beef sires to allow users to rank the
      bulls according to expected merit of their progeny in specific production
      systems.

PMID- 17430951
TI  - Genetic analysis of milk urea nitrogen and lactose and their relationships with
      other production traits in Canadian Holstein cattle.
AB  - The objective of this research was to estimate heritabilities of milk urea
      nitrogen (MUN) and lactose in the first 3 parities and their genetic
      relationships with milk, fat, protein, and SCS in Canadian Holsteins. Data were a
      random sample of complete herds (60,645 test day records of 5,022 cows from 91
      herds) extracted from the edited data set, which included 892,039 test-day
      records of 144,622 Holstein cows from 4,570 herds. A test-day animal model with
      multiple-trait random regression and the Gibbs sampling method were used for
      parameter estimation. Regression curves were modeled using Legendre polynomials
      of order 4. A total of 6 separate 4-trait analyses, which included MUN, lactose,
      or both (yield or percentage) with different combinations of production traits
      (milk, fat and protein yield, fat and protein percentages, and somatic cell
      score) were performed. Average daily heritabilities were moderately high for MUN
      (from 0.384 to 0.414), lactose kilograms (from 0.466 to 0.539), and lactose
      percentage (from 0.478 to 0.508). Lactose yield was highly correlated with milk
      yield (0.979). Lactose percentage and MUN were not genetically correlated with
      milk yield. However, lactose percentage was significantly correlated with somatic
      cell score (-0.202). The MUN was correlated with fat (0.425) and protein
      percentages (0.20). Genetic correlations among parities were high for MUN,
      lactose percentage, and yield. Estimated breeding values (EBV) of bulls for MUN
      were correlated with fat percentage EBV (0.287) and EBV of lactose percentage
      were correlated with lactation persistency EBV (0.329). Correlations between
      lactose percentage and MUN with fertility traits were close to zero, thus
      diminishing the potential of using those traits as possible indicators of
      fertility.

PMID- 17430952
TI  - Genetic evaluation of stillbirth in United States Holsteins using a sire-maternal
      grandsire threshold model.
AB  - A sire-maternal grandsire threshold model was used for genetic evaluation of
      stillbirth in US Holsteins. Calving ease and stillbirth records for herds
      reporting at least 10 dead calves were extracted from the Animal Improvement
      Programs Laboratory database. About half of the 14 million calving ease records
      in the database had a known livability score, mostly from herds processed by
      Dairy Records Management Systems (Raleigh, NC). Calf livability scores of 2 and
      3, representing calves born dead and calves that died within 48 h of parturition,
      respectively, were combined into a single category. The model included effects of
      herd-year, year-season, parity-sex, sire, birth year group of sire, maternal
      grandsire (MGS), and birth year group of MGS. Herd-year, sire, and MGS were
      random effects. Mean predicted transmitting abilities, expressed as the expected
      percentage of stillbirths, were 7.9 and 8.6 for direct and maternal stillbirths,
      respectively. Mean reliabilities for both the direct and maternal effects were
      45%. Correlations among domestic and Interbull stillbirth solutions on the
      underlying scale for bulls with at least 90% reliability ranged from 0.63 to 0.90
      across countries for direct stillbirths and from 0.69 to 0.96 for maternal
      stillbirths, indicating that results were generally consistent with those from
      other countries. There was no evidence of a genetic trend for either trait. More
      complete recording of stillbirth scores would improve reliabilities and could
      allow for evaluations of other breeds.

PMID- 17430953
TI  - Stillbirth (co)variance components for a sire-maternal grandsire threshold model
      and development of a calving ability index for sire selection.
AB  - (Co)variance components for stillbirth in US Holsteins were estimated under a
      sire-maternal grandsire threshold model using subsets of data from the national
      calving ease database, which includes over 6 million calving records with
      associated stillbirth scores. Stillbirth was coded as a binomial trait indicating
      whether the calf was alive 48 h postpartum. Records were selected for calves
      whose sire and maternal grandsire (MGS) were among the 2,600 most frequently
      appearing bulls (2,578 sires and 2,586 MGS). Herd-years were required to contain
      at least 20 records and only single births were used. After editing, the data set
      included 2,083,979 calving records from 5,765 herds and 33,304 herd-years. Six
      sample datasets of approximately 250,000 records each were created by randomly
      selecting herd codes. Quasi-REML and Bayesian approaches were used to estimate
      (co)variance components from each sample. The model included fixed year-season,
      parity-sex, birth year group of sire, and birth year group of MGS effects and
      random herd-year, sire, MGS, and residual effects. Quasi-REML and Bayesian
      analyses produced similar results, although the Bayesian estimates were slightly
      larger. Marginal posterior means (and standard deviations) from the Bayesian
      analysis averaged 0.0085 (0.0015), 0.0181 (0.0020), 0.0872 (0.0538), and 0.00410
      (0.0001) for sire, MGS, and herd-year variances and the sire-MGS covariance,
      respectively. Mean direct and maternal heritabilities were 0.030 (0.003) and
      0.058 (0.005), respectively, and the mean genetic correlation between the 2
      effects was -0.02 (0.16). A calving ability index combining stillbirth (SB) and
      calving ease (CE) was developed for inclusion in the Lifetime Net Merit index.
      The index was calculated as -4(sire CE)-3(daughter CE)-4(sire SB) -8(daughter
      SB).

PMID- 17430954
TI  - Consequences of selection for yield traits on calving ease performance.
AB  - The impact of different breeding goals on the genetic response for calving ease
      (CE) and yield traits was studied in the Basque Holstein cattle population. The
      economic value for CE was estimated with a bioeconomic model, using Basque
      production and market circumstances and taking into account the categorical
      nature of CE. The economic value for CE was -18.03 euros/cow per calving interval
      per liability unit. This value was relatively insensitive to changes in the
      market price of animals but was more sensitive to changes in the incidence of
      dystocia. Records from parities between 1995 and 2002 were used for the
      estimation of genetic parameters for yield (actual milk, fat, and protein yield)
      and CE using a multivariate model. Linear sire models for yield traits and a
      threshold sire-maternal grandsire model for CE were used. A Holstein population
      was simulated to determine the consequences of including CE in the breeding goal.
      Three selection strategies were considered: 1) selection only on yield traits, 2)
      selection on yield and direct CE (DCE), and 3) selection on yield, DCE, and
      maternal CE (MCE). Selection on yield traits only resulted in a slight reduction
      of dystocia. Selection strategies in which DCE or DCE and MCE were included in
      the breeding goal did not improve the genetic response for DCE and MCE obtained
      with the first selection strategy. Genetic responses were also calculated using
      the 2.5th, 50th, and 97.5th percentiles of posterior densities of genetic
      correlations between DCE and MCE and yield traits. Because responses in CE were
      sensitive to deviations in estimates of genetic parameters, the inclusion of CE
      in the monitoring scheme is recommended. Genetic evaluation of bulls for CE is of
      considerable value because it provides farmers with the opportunity to use
      assortative matings of sires with favorable estimated breeding values for DCE to
      primiparous cows.

PMID- 17430955
TI  - A cost and returns evaluation of alternative dairy products to determine capital
      investment and operational feasibility of a small-scale dairy processing
      facility.
AB  - This study examines the economic feasibility of 50- and 500-cow dairy processing
      facilities for fluid milk, yogurt, and cheese. Net present value and internal
      rate of return calculations for projected costs and returns over a 10-yr period
      indicate that larger yogurt and cheese processing plants offer the most
      profitable prospects, whereas a smaller yogurt plant would break even. A smaller
      cheese plant would have insufficient returns to cover the cost of capital, and
      fluid milk processing at either scale is economically infeasible. Economic
      success in processing is greatly contingent upon individual business, financial
      management, and marketing skills.

PMID- 17430956
TI  - Longitudinal monitoring of Listeria monocytogenes contamination patterns in a
      farmstead dairy processing facility.
AB  - Contamination of dairy products with Listeria monocytogenes is a concern because
      multiple human listeriosis outbreaks have been linked to contaminated cheese and
      dairy products. Dairy production on farmstead operations may be a particular
      concern because L. monocytogenes is also an animal pathogen that can be shed by
      ruminants with and without clinical symptoms; physical proximity between
      production animal and dairy processing facilities may thus provide a higher risk
      for introduction of L. monocytogenes into the dairy production process. To better
      understand the risks of L. monocytogenes contamination associated with farmstead
      dairy production, samples from a farmstead dairy processing operation and the
      milking barn of the directly adjacent dairy sheep operation were tested for L.
      monocytogenes over a 3-yr period. Prevalence of L. monocytogenes for samples
      collected on the farm (n = 85) and the dairy production facility (n = 674) was
      9.4 and 2.7%, respectively. Molecular subtyping using automated EcoRI ribotyping
      of L. monocytogenes isolates revealed that distinct subtypes were associated with
      the dairy production facility and the farm's milking parlor. Although a total of
      5 and 4 different ribotypes were identified among isolates obtained from the
      dairy production facility and the milking parlor, respectively, only 1 ribotype
      (DUP-1030A) was isolated from both. Different ribotypes were predominant among
      isolates from the dairy production facility (ribotype DUP-1052A, representing 15
      of 18 isolates) and the farm's milking parlor (ribotype DUP-1039A, representing 4
      of 8 isolates); each of these ribotypes appeared to persist over time in the
      respective area. Our data support that i) in farmstead dairy processing
      facilities, L. monocytogenes present on the farm can largely be prevented from
      being introduced into the processing facility; and ii) L. monocytogenes can
      persist on farm and in processing areas, providing a potential high-risk source
      for contamination. Preventing cross contamination between dairy production and
      processing facilities and control of persistent L. monocytogenes are thus
      critical to assuring the microbial safety of farmstead dairy products.

PMID- 17430957
TI  - A model describing Debaryomyces hansenii growth and substrate consumption during
      a smear soft cheese deacidification and ripening.
AB  - A mechanistic model for Debaryomyces hansenii growth and substrate consumption,
      lactose conversion into lactate by lactic acid bacteria, as well as lactose and
      lactate transfer from the core toward the rind was established. The model
      described the first step (14 d) of the ripening of a smear soft cheese and
      included the effects of temperature and relative humidity of the ripening chamber
      on the kinetic parameters. Experimental data were collected from experiments
      carried out in an aseptic pilot scale ripening chamber under 9 different
      combinations of temperature (8, 12, and 16 degrees C) and relative humidity (85,
      93, and 99%) according to a complete experimental design. The model considered
      the cheese as a system with 2 compartments (rind and core) and included 5 state
      evolution equations and 16 parameters. The model succeeded in predicting D.
      hansenii growth and lactose and lactate concentrations during the first step of
      ripening (curd deacidification) in core and rind. The nonlinear data-fitting
      method allowed the determination of tight confidence intervals for the model
      parameters. The residual standard error (RSE) between model predictions and
      experimental data was close to the experimental standard deviation between
      repeated experiments.

PMID- 17430958
TI  - A field study on fertility and purity of sex-sorted cattle sperm.
AB  - The study assessed the fertility and purity of sexed semen used for inseminating
      Holstein-Friesian heifers in commercial dairy herds. Sex-sorted semen from 4
      proven Holstein-Friesian bulls and available under commercial conditions was used
      on nulliparous Holstein heifers reared on 61 dairy farms of northern Italy. Data
      from 536 artificial inseminations with pregnancy diagnosis and 258 calvings were
      analyzed using the logistic regression procedure. The effects of year and season
      of insemination or calving, age at insemination or calving, heifer inbreeding,
      and the sperm dose used for insemination on the probability of a positive
      pregnancy diagnosis or of the birth of a female calf, respectively, were studied.
      The overall pregnancy rate for sexed semen was 51% and was affected by year of
      insemination and bull. Heifers inseminated with sexed semen from 2 bulls had
      lower pregnancy rates than heifers inseminated with sexed semen from other bulls.
      Purity of the sexed sperm, based on the proportion of female calves, was 87% and
      this percentage was not affected by explanatory variables included in the
      logistic regression. The results demonstrate that bulls differ in terms of
      fertility of their sexed semen. Careful selection of the insemination sires used
      for sorted semen is advisable for avoiding low fertility inseminations.

PMID- 17430959
TI  - Danish stable schools for experiential common learning in groups of organic dairy
      farmers.
AB  - The farmer field school (FFS) is a concept for farmers' learning, knowledge
      exchange, and empowerment that has been developed and used in developing
      countries. In Denmark, a research project focusing on explicit non-antibiotic
      strategies involves farmers who have actively expressed an interest in phasing
      out antibiotics from their herds through promotion of animal health. One way of
      reaching this goal was to form participatory focused farmer groups in an FFS
      approach, which was adapted to Danish conditions and named "stable schools." Four
      stable schools were established and went through a 1-yr cycle with 2 visits at
      each of the 5 or 6 farms connected to each group. A facilitator was connected to
      each group whose role was to write the meeting agenda together with the host
      farmer, direct the meeting, and write the minutes to send to the group members
      after the meeting. Through group focus interviews and individual semistructured
      qualitative interviews of all participants, the approach of the farmers' goal
      directed work toward a common goal was judged to be very valuable and fruitful
      and based on a common learning process. Complex farming situations were the focus
      of all groups and in this context, problems were identified and solutions
      proposed based on each farmer's individual goals. In this article, we describe
      the experiences of 4 stable school groups (each comprising farmers and a
      facilitator), and the common process of building a concept that is suitable for
      Danish organic dairy farming.

PMID- 17430960
TI  - Identifying efficient dairy producers using data envelopment analysis.
AB  - The objective of this research was to calculate the efficiency of a group of
      Pennsylvania dairy farms to determine factors that contributed to efficiency in
      production and business management. Data envelopment analysis (DEA) was used to
      estimate the efficiency. Two models were developed to measure the efficient use
      of physical (land, cows, and labor) inputs to produce physical (milk and
      butterfat) outputs, and the use of physical and economic (debt capital) inputs to
      produce physical and economic (income) outputs. The results showed that about 29%
      of the producers in our sample were DEA-efficient and demonstrated that there was
      no combination of inputs used by efficient producers that was best. In addition,
      the method of analysis illustrated the benefits of DEA in that it is possible to
      identify the set of efficient producers that inefficient producers can benchmark
      to in an effort to achieve similar levels of efficiency. Finally, the analysis
      demonstrated that producers should not benchmark to the highest level of
      production, but rather should combine resources in land, labor, cows, and debt
      capital to achieve an efficient level of production, which indeed may be less
      than the maximum production level of the group.

PMID- 17430961
TI  - Use of herd solutions from a random regression test-day model for diagnostic
      dairy herd management.
AB  - In a random regression test-day model, environmental effects in addition to
      individual animal factors can be included and analyzed. Moreover, instead of herd
      year classification of the management groups, the herd-test-day classification
      within the model better accounts for month-to-month short-term environmental
      variation in production and somatic cell count (SCC) traits. The herd management
      levels of milk yield (milk deviation from whole-country mean, kilograms/day),
      protein and fat concentration (protein and fat deviation, %), and SCC (SCC
      deviation, 1,000 cells/mL) are used in the dairy herd management Web application
      "Maitoisa" (in English, "Milky"). This management tool helps to recognize several
      management problems. For recognition of systematic patterns and single unusual
      test-days, a monthly time-trend analysis was developed to smooth the random
      fluctuations and display the yearly production pattern. In addition to analyzing
      single test-day deviations from the mean, modeled herd solutions assist users in
      identifying repeated phenomena and enable the forecasting of the management
      pattern for the subsequent year. The solutions are displayed either as tables or
      graphs plotted by calendar months. In addition to management effects of the
      farmer's own herd, he or she can request country or region percentiles to be
      displayed in the graphs. The Web service has been offered to farmers and dairy
      advisors since 2001, and it has proved to be a powerful tool for herd monitoring
      and planning.

PMID- 17430962
TI  - Expected net present value of pure and mixed sexed semen artificial insemination
      strategies in dairy heifers.
AB  - Sexed semen has been a long-anticipated tool for dairy farmers to obtain more
      heifer calves, but challenges exist for integrating sexed semen into commercial
      dairy farm reproduction programs. The decreased conception rates (CR) experienced
      with sexed semen make virgin heifers better suited for insemination with sexed
      semen than lactating dairy cows. This research sought to identify when various
      sexed semen breeding strategies provided higher expected net present value (NPV)
      than conventional artificial insemination (AI) breeding schemes, indicating which
      breeding scheme is advisable under various scenarios. Budgets were developed to
      calculate the expected NPV of various AI breeding strategies incorporating
      conventional (non-sexed) and sexed semen. In the base budgets, heifer and bull
      calf values were held constant at $500 and $110, respectively. The percentage of
      heifers expected to be born after breeding with conventional and sexed semen used
      was 49.2 and 90%, respectively. Breeding costs per AI were held constant at
      $15.00 per AI for conventional semen and $45.00 per AI for sexed semen of
      approximately the same genetic value. Conventional semen CR of 58 and 65% were
      used, and an AI submission rate was set at 100%. Breeding strategies with sexed
      semen were assessed for breakeven heifer calf values and sexed semen costs to
      obtain a NPV equal to that achieved with conventional semen. Breakeven heifer
      calf values for pure sexed semen strategies with a constant 58 and 65% base CR in
      which sexed semen achieved 53% of the base CR are $732.11 and $664.26,
      respectively. Breakeven sexed semen costs per AI of $17.16 and $22.39, compared
      with $45.00 per AI, were obtained to obtain a NPV equal to that obtained with
      pure conventional semen for base CR of 58 and 65%, respectively. The strategy
      employing purely sexed semen, with base CR of both 58 and 65%, yielded a lower
      NPV than purely conventional semen in all but the best-case scenario in which
      sexed semen provides 90% of the CR of conventional semen. Other potential
      advantages of sexed semen that were not quantified in the scenarios include
      biosecurity-related concerns, decreased dystocia due to increased numbers of
      heifer calves, and implications for internal herd growth.

PMID- 17430963
TI  - Influence of secondary structure on kinetics and reaction mechanism of DNA
      hybridization.
AB  - Hybridization of nucleic acids with secondary structure is involved in many
      biological processes and technological applications. To gain more insight into
      its mechanism, we have investigated the kinetics of DNA
      hybridization/denaturation via fluorescence resonance energy transfer (FRET) on
      perfectly matched and single-base-mismatched DNA strands. DNA hybridization shows
      non-Arrhenius behavior. At high temperature, the apparent activation energies of
      DNA hybridization are negative and independent of secondary structure. In
      contrast, when temperature decreases, the apparent activation energies of DNA
      hybridization change to positive and become structure dependent. The large
      unfavorable enthalpy of secondary structure melting is compensated for by
      concomitant duplex formation. Based on our results, we propose a reaction
      mechanism about how the melting of secondary structure influences the
      hybridization process. A significant point in the mechanism is that the rate
      limiting step switches along with temperature variation in the hybridization
      process of structured DNA, because the free energy profile of hybridization in
      structured DNA varies with the variation in temperature.

PMID- 17430964
TI  - The domain structure of Helicobacter pylori DnaB helicase: the N-terminal domain
      can be dispensable for helicase activity whereas the extreme C-terminal region is
      essential for its function.
AB  - Hexameric DnaB type replicative helicases are essential for DNA strand unwinding
      along with the direction of replication fork movement. These helicases in general
      contain an amino terminal domain and a carboxy terminal domain separated by a
      linker region. Due to the lack of crystal structure of a full-length DnaB like
      helicase, the domain structure and function of these types of helicases are not
      clear. We have reported recently that Helicobacter pylori DnaB helicase is a
      replicative helicase in vitro and it can bypass Escherichia coli DnaC activity in
      vivo. Using biochemical, biophysical and genetic complementation assays, here we
      show that though the N-terminal region of HpDnaB is required for conformational
      changes between C6 and C3 rotational symmetry, it is not essential for in vitro
      helicase activity and in vivo function of the protein. Instead, an extreme
      carboxy terminal region and an adjacent unique 34 amino acid insertion region
      were found to be essential for HpDnaB activity suggesting that these regions are
      important for proper folding and oligomerization of this protein. These results
      confer great potential in understanding the domain structures of DnaB type
      helicases and their related function.

PMID- 17430965
TI  - Investigation of spectral conversion of d(TTAGGG)4 and d(TTAGGG)13 upon potassium
      titration by a G-quadruplex recognizer BMVC molecule.
AB  - We have introduced a G-quadruplex-binding ligand, 3,6-bis(1-methyl-4
      vinylpyridinium)carbazole diiodide (BMVC), to verify the major structure of
      d(T2AG3)4 (H24) in potassium solution and examine the structural conversion of
      H24 in sodium solution upon potassium titration. The studies of circular
      dichroism, induced circular dichroism, spectral titration and gel competition
      have allowed us to determine the binding mode and binding ratio of BMVC to the
      H24 in solution and eliminate the parallel form as the major G-quadruplex
      structure. Although the mixed-type form could not be eliminated as a main
      component, the basket and chair forms are more likely the main components of H24
      in potassium solution. In addition, the circular dichroism spectra and the job
      plots reveal that a longer telomeric sequence d(T2AG3)13 (H78) could form two
      units of G4 structure both in sodium or potassium solutions. Of particular
      interest is that no appreciable change on the induced circular dichroism spectra
      of BMVC is found during the change of the circular dichroism patterns of H24 upon
      potassium titration. Considering similar spectral conversion detected for H24 and
      a long sequence H78 together with the G4 structure stabilized by BMVC, it is
      therefore unlikely that the rapid spectral conversion of H24 and H78 is due to
      structural change between different types of the G4 structures. With reference to
      the circular dichroism spectra of d(GAA)7 and d(GAAA)5, we suggest that the
      spectral conversion of H24 upon potassium titration is attributed to fast ion
      exchange resulting in different loop base interaction and various hydrogen
      bonding effects.

PMID- 17430966
TI  - Revision of the nonequilibrium thermal dissociation and stringent washing
      approaches for identification of mixed nucleic acid targets by microarrays.
AB  - Microarray experiments typically involve washing steps that remove hybridized
      nonspecific targets with the purpose of improving the signal-to-noise ratio. The
      quality of washing ultimately affects downstream analysis of the microarray and
      interpretation. The paucity of fundamental studies directed towards understanding
      the dissociation of mixed targets from microarrays makes the development of
      meaningful washing/dissociation protocols difficult. To fill the void, we
      examined activation energies and preexponential coefficients of 47 perfect match
      (PM) and double-mismatch (MM) duplex pairs to discover that there was no
      statistical difference between the kinetics of the PM and MM duplexes. Based on
      these findings, we evaluated the nonequilibrium thermal dissociation (NTD)
      approach, which has been used to identify specific microbial targets in mixed
      target samples. We found that the major premises for various washing protocols
      and the NTD approach might be seriously compromised because: (i) nonspecific
      duplexes do not always dissociate before specific ones, and (ii) the relationship
      between dissociation rates of the PM and MM duplexes depends on temperature and
      duplex sequence. Specifically for the NTD, we show that previously suggested use
      of reference curves, indices of curves and temperature ramps lead to erroneous
      conclusions.

PMID- 17430967
TI  - Use of a novel Forster resonance energy transfer method to identify locations of
      site-bound metal ions in the U2-U6 snRNA complex.
AB  - U2 and U6 snRNAs pair to form a phylogenetically conserved complex at the
      catalytic core of the spliceosome. Interactions with divalent metal ions,
      particularly Mg(II), at specific sites are essential for its folding and
      catalytic activity. We used a novel Forster resonance energy transfer (FRET)
      method between site-bound luminescent lanthanide ions and a covalently attached
      fluorescent dye, combined with supporting stoichiometric and mutational studies,
      to determine locations of site-bound Tb(III) within the human U2-U6 complex. At
      pH 7.2, we detected three metal-ion-binding sites in: (1) the consensus ACACAGA
      sequence, which forms the internal loop between helices I and III; (2) the four
      way junction, which contains the conserved AGC triad; and (3) the internal loop
      of the U6 intra-molecular stem loop (ISL). Binding at each of these sites is
      supported by previous phosphorothioate substitution studies and, in the case of
      the ISL site, by NMR. Binding of Tb(III) at the four-way junction and the ISL
      sites was found to be pH-dependent, with no ion binding observed below pH 6 and
      7, respectively. This pH dependence of metal ion binding suggests that the local
      environment may play a role in the binding of metal ions, which may impact on
      splicing activity.

PMID- 17430968
TI  - Thermodynamics and NMR studies on Duck, Heron and Human HBV encapsidation
      signals.
AB  - Hepatitis B virus (HBV) replication is initiated by binding of its reverse
      transcriptase (P) to the apical stem-loop (AL) and primer loop (PL) of epsilon, a
      highly conserved RNA element at the 5'-end of the RNA pregenome. Mutation studies
      on duck/heron and human in vitro systems have shown similarities but also
      differences between their P-epsilon interaction. Here, NMR and UV thermodynamic
      data on AL (and PL) from these three species are presented. The stabilities of
      the duck and heron ALs were found to be similar, and much lower than that of
      human. NMR data show that this low stability stems from an 11-nt internal bulge
      destabilizing the stem of heron AL. In duck, although structured at low
      temperature, this region also forms a weak point as its imino resonances broaden
      to disappearance between 30 and 35 degrees C well below the overall AL melting
      temperature. Surprisingly, the duck- and heron ALs were both found to be capped
      by a stable well-structured UGUU tetraloop. All avian ALs are expected to adhere
      to this because of their conserved sequence. Duck PL is stable and structured
      and, in view of sequence similarities, the same is expected for heron - and human
      PL.

PMID- 17430969
TI  - Error-pooling-based statistical methods for identifying novel temporal
      replication profiles of human chromosomes observed by DNA tiling arrays.
AB  - Statistical analysis on tiling array data is extremely challenging due to the
      astronomically large number of sequence probes, high noise levels of individual
      probes and limited number of replicates in these data. To overcome these
      difficulties, we first developed statistical error estimation and weighted ANOVA
      modeling approaches to high-density tiling array data, especially the former
      based on an advanced error-pooling method to accurately obtain heterogeneous
      technical error of small-sample tiling array data. Based on these approaches, we
      analyzed the high-density tiling array data of the temporal replication patterns
      during cell-cycle S phase of synchronized HeLa cells on human chromosomes 21 and
      22. We found many novel temporal replication patterns, identifying about 26% of
      over 1 million tiling array sequence probes with significant differential
      replication during the four 2-h time periods of S phase. Among these
      differentially replicated probes, 126 941 sequence probes were matched to 417
      known genes. The majority of these genes were found to be replicated within one
      or two consecutive time periods, while the others were replicated at two non
      consecutive time periods. Also, coding regions found to be more differentially
      replicated in particular time periods than noncoding regions in the gene-poor
      chromosome 21 (25% differentially replicated among genic probes versus 18.6%
      among intergenic probes), while such a phenomenon was less prominent in gene-rich
      chromosome 22. A rigorous statistical testing for local proximity of
      differentially replicated genic and intergenic probes was performed to identify
      significant stretches of differentially replicated sequence regions. From this
      analysis, we found that adjacent genes were frequently replicated at different
      time periods, potentially implying the existence of quite dense replication
      origins. Evaluating the conditional probability significance of identified gene
      ontology terms on chromosomes 21 and 22, we detected some over-represented
      molecular functions and biological processes among these differentially
      replicated genes, such as the ones relevant to hydrolase, transferase and
      receptor-binding activities. Some of these results were confirmed showing >70%
      consistency with cDNA microarray data that were independently generated in
      parallel with the tiling arrays. Thus, our improved analysis approaches
      specifically designed for high-density tiling array data enabled us to reliably
      and sensitively identify many novel temporal replication patterns on human
      chromosomes.

PMID- 17430970
TI  - Topoisomerase II, scaffold component, promotes chromatin compaction in vitro in a
      linker-histone H1-dependent manner.
AB  - TopoisomeraseII (Topo II) is a major component of chromosomal scaffolds and
      essential for mitotic chromosome condensation, but the mechanism of this action
      remains unknown. Here, we used an in vitro chromatin reconstitution system in
      combination with atomic force and fluorescence microscopic analyses to determine
      how Topo II affects chromosomal structure. Topo II bound to bare DNA and clamped
      the two DNA strands together, even in the absence of ATP. In addition, Topo II
      promoted chromatin compaction in a manner dependent on histone H1 but independent
      of ATP. Histone H1-induced 30-nm chromatin fibers were converted into a large
      complex by Topo II. Fluorescence microscopic analysis of the Brownian motion of
      chromatin stained with 4',6-diamidino-2-phenylindole showed that the
      reconstituted chromatin became larger following the addition of Topo II in the
      presence but not the absence of histone H1. Based on these findings, we propose
      that chromatin packing is triggered by histone H1-dependent, Topo II-mediated
      clamping of DNA strands.

PMID- 17430971
TI  - R.KpnI, an HNH superfamily REase, exhibits differential discrimination at non
      canonical sequences in the presence of Ca2+ and Mg2+.
AB  - KpnI REase recognizes palindromic sequence, GGTACC, and forms complex in the
      absence of divalent metal ions, but requires the ions for DNA cleavage. Unlike
      most other REases, R.KpnI shows promiscuous DNA cleavage in the presence of Mg2+.
      Surprisingly, Ca2+ suppresses the Mg2+-mediated promiscuous activity and induces
      high fidelity cleavage. To further analyze these unique features of the enzyme,
      we have carried out DNA binding and kinetic analysis. The metal ions which
      exhibit disparate pattern of DNA cleavage have no role in DNA recognition. The
      enzyme binds to both canonical and non-canonical DNA with comparable affinity
      irrespective of the metal ions used. Further, Ca2+-imparted exquisite specificity
      of the enzyme is at the level of DNA cleavage and not at the binding step. With
      the canonical oligonucleotides, the cleavage rate of the enzyme was comparable
      for both Mg2+- and Mn2+-mediated reactions and was about three times slower with
      Ca2+. The enzyme discriminates non-canonical sequences poorly from the canonical
      sequence in Mg2+-mediated reactions unlike any other Type II REases, accounting
      for the promiscuous behavior. R.KpnI, thus displays properties akin to that of
      typical Type II REases and also endonucleases with degenerate specificity in its
      DNA recognition and cleavage properties.

PMID- 17430972
TI  - A chimeric cysteine protease of Plasmodium berghei engineered to resemble the
      Plasmodium falciparum protease falcipain-2.
AB  - The cysteine proteases falcipain-2 and falcipain-3 are hemoglobinases and
      potential targets for chemotherapy directed against Plasmodium falciparum, the
      most important human malaria parasite. Most in vivo evaluations of candidate
      antimalarials are conducted in murine malaria models, and falcipain homologs from
      rodent malaria parasites differ importantly from falcipain-2 and falcipain-3. We
      expressed berghepain-2, the single homolog of falcipain-2 and falcipain-3 of the
      rodent parasite P. berghei, in Escherichia coli, and characterized the refolded
      active enzyme. Berghepain-2 was biochemically very similar to the previously
      characterized rodent plasmodial protease vinckepain-2, but differed from
      falcipain-2 and falcipain-3 in its fine substrate and inhibitor specificity. We
      then used homology modeling and evolutionary trace analysis to predict key amino
      acids that mediate functional differences between falcipain-2 and berghepain-2.
      Thirteen amino acids were sequentially altered to replace berghepain-2 residues
      with those in falcipain-2. Mutant enzymes varied in activity and sensitivity to
      inhibitors. A berghepain-2 mutant with eight substitutions retained good activity
      and demonstrated fine substrate and inhibitor sensitivity more similar to that of
      falcipain-2 than berghepain-2. These results suggest that, to facilitate drug
      discovery, we can produce mutant animal model malaria parasites with biochemical
      properties more like those of the key drug target, P. falciparum.

PMID- 17430973
TI  - Chimeric protein for selective cell attachment onto cellulosic substrates.
AB  - We have developed a fusion protein (CBD-LG) incorporating a cellulose-binding
      domain and an antibody binding domain, protein LG, to provide an adaptor molecule
      for cell separation with regenerated cellulose hollow fiber arrays. A single
      hollow fiber cell adhesion assay utilizing a CD34+ cell line, KG1a, was used to
      investigate whether ligand affinity interactions were strong enough for cell
      attachment and separation. CBD-LG efficiently captured CD34+ cells labeled with
      the mouse IgG2a monoclonal antibody MHCD3400. However, it was not possible to
      bind CD34+ cells labeled with an IgG1 antibody (HPCA-2). The low affinity of HPCA
      2 for LG was overcome by secondary antibodies: KG1a cells that were dual labeled
      with HPCA-2 followed by rat anti-mouse IgG1 adhered inside hollow fibers coated
      with CBD-LG. Alternatively, immobilized rabbit polyclonal anti-mouse IgG1
      captured cells labeled with HPCA-2. The development of an adaptor molecule to
      display recombinant domains at the surface of hollow fibers will be an effective
      tool to investigate cellular ligand-receptor interactions, a necessary step in
      the development of hollow fiber bioreactors for manufacture of human cellular
      products.

PMID- 17430974
TI  - A strategy for high-level expression of soluble and functional human interferon
      alpha as a GST-fusion protein in E. coli.
AB  - Escherichia coli is the most extensively used host for the production of
      recombinant proteins. However, most of the eukaryotic proteins are typically
      obtained as insoluble, misfolded inclusion bodies that need solubilization and
      refolding. To achieve high-level expression of soluble recombinant human
      interferon alpha (rhIFNalpha) in E. coli, we have first constructed a recombinant
      expression plasmid (pGEX-hIFNalpha2b), in which we merged the hIFNalpha2b cDNA
      with the glutathione S-transferase (GST) coding sequence downstream of the tac
      inducible promoter. Using this plasmid, we have achieved 70% expression of
      soluble rhIFNalpha2b as a GST fusion protein using E. coli BL21 strain, under
      optimized environmental factors such as culture growth temperature and inducer
      (IPTG) concentration. However, release of the IFN moiety from the fusion protein
      by thrombin digestion was not optimal. Therefore, we have engineered the
      expression cassette to optimize the amino acid sequence at the GST-IFN junction
      and to introduce E. coli preferred codon within the thrombin cleavage site. We
      have used the engineered plasmid (pGEX-Delta-hIFNalpha2b) and the modified E.
      coli trxB(-)/gor(-) (Origami) strain to overcome the problem of removing the GST
      moiety while expressing soluble rhIFNalpha2b. Our results show the production of
      soluble and functional rhIFNalpha2b at a yield of 100 mg/l, without optimization
      of any step of the process. The specific biological activity of the purified
      soluble rhIFNalpha2b was equal to 2.0 x 10(8) IU/mg when compared with the WHO
      IFNalpha standard. Our data are the first to show that high yield production of
      soluble and functional rhIFNalpha2b tagged with GST can be achieved in E. coli.

PMID- 17430975
TI  - Molecular modeling suggests induced fit of Family I carbohydrate-binding modules
      with a broken-chain cellulose surface.
AB  - Cellobiohydrolases are the most effective single component of fungal cellulase
      systems; however, their molecular mode of action on cellulose is not well
      understood. These enzymes act to detach and hydrolyze cellodextrin chains from
      crystalline cellulose in a processive manner, and the carbohydrate-binding module
      (CBM) is thought to play an important role in this process. Understanding the
      interactions between the CBM and cellulose at the molecular level can assist
      greatly in formulating selective mutagenesis experiments to confirm the function
      of the CBM. Computational molecular dynamics was used to investigate the
      interaction of the CBM from Trichoderma reesei cellobiohydrolase I with a model
      of the (1,0,0) cellulose surface modified to display a broken chain. Initially,
      the CBM was located in different positions relative to the reducing end of this
      break, and during the simulations it appeared to translate freely and randomly
      across the cellulose surface, which is consistent with its role in processivity.
      Another important finding is that the reducing end of a cellulose chain appears
      to induce a conformational change in the CBM. Simulations show that the tyrosine
      residues on the hydrophobic surface of the CBM, Y5, Y31 and Y32 align with the
      cellulose chain adjacent to the reducing end and, importantly, that the fourth
      tyrosine residue in the CBM (Y13) moves from its internal position to form van
      der Waals interactions with the cellulose surface. As a consequence of this
      induced change near the surface, the CBM straddles the reducing end of the broken
      chain. Interestingly, all four aromatic residues are highly conserved in Family I
      CBM, and thus this recognition mechanism may be universal to this family.

PMID- 17430976
TI  - Characterisation of IRTKS, a novel IRSp53/MIM family actin regulator with
      distinct filament bundling properties.
AB  - IRSp53 is a scaffold protein that contains an IRSp53/MIM homology domain (IMD)
      that bundles actin filaments and interacts with the small GTPase Rac. IRSp53 also
      binds to the small GTPase Cdc42 and to Scar/WAVE and Mena/VASP proteins to
      regulate the actin cytoskeleton. We have characterised a novel IMD-containing
      protein, insulin receptor tyrosine kinase substrate (IRTKS), which has widespread
      tissue distribution, is a substrate for the insulin receptor and binds Rac.
      Unlike IRSp53, IRTKS does not interact with Cdc42. Expression of IRTKS induces
      clusters of short actin bundles rather than filopodia-like protrusions. This
      difference may be attributable to a short carboxyl-terminal (Ct) extension
      present on IRTKS, which resembles a WASP-homology 2 (WH2) motif. Addition of the
      Ct extension to IRSp53 causes an apparent shortening of bundles induced by the
      IMD in vitro, and in cultured cells, suggesting that the Ct extension of IRTKS
      modulates the organising activity of the IMD. Lastly, we could not detect actin
      monomer sequestration by the Ct extension of IRTKS as would be expected with a
      conventional WH2 motif, but it did interact with actin filaments.

PMID- 17430977
TI  - Experimental evidence for the influence of molecular crowding on nuclear
      architecture.
AB  - Many compounds in the cell nucleus are structurally organized. To assess the
      influence of structural organization on nuclear function, we investigated the
      physical mechanisms of structure formation by using molecular crowding as a
      parameter for nuclear integrity. Molecular crowding promotes compaction of
      macromolecular compounds depending on their size and shape without the need for
      site-specific interactions. HeLa and MCF7 cells were incubated with hypertonic
      medium to increase crowding of their macromolecular content as a result of the
      osmotic loss of water. Supplementation of sucrose, sorbitol or NaCl to the growth
      medium shifted nuclear organization, observed by fluorescence and electron
      microscopy, towards compaction of chromatin and segregation of other nuclear
      compounds. With increasing hypertonic load and incubation time, this nuclear re
      organization proceeded gradually, irrespective of the substances used, and
      reversibly relaxed to a regular phenotype upon re-incubation of cells in isotonic
      growth medium. Gradual and reversible re-organization are major features of
      controlled de-mixing by molecular crowding. Of fundamental importance for nuclear
      function, we discuss how macromolecular crowding could account for the
      stabilization of processes that involve large, macromolecular machines.

PMID- 17430978
TI  - Bayesian methods in bioinformatics and computational systems biology.
AB  - Bayesian methods are valuable, inter alia, whenever there is a need to extract
      information from data that are uncertain or subject to any kind of error or noise
      (including measurement error and experimental error, as well as noise or random
      variation intrinsic to the process of interest). Bayesian methods offer a number
      of advantages over more conventional statistical techniques that make them
      particularly appropriate for complex data. It is therefore no surprise that
      Bayesian methods are becoming more widely used in the fields of genetics,
      genomics, bioinformatics and computational systems biology, where making sense of
      complex noisy data is the norm. This review provides an introduction to the
      growing literature in this area, with particular emphasis on recent developments
      in Bayesian bioinformatics relevant to computational systems biology.

PMID- 17430979
TI  - Sensitivity of Polygonum aviculare seeds to light as affected by soil moisture
      conditions.
AB  - BACKGROUND AND AIMS: It has been hypothesized that soil moisture conditions could
      affect the dormancy status of buried weed seeds, and, consequently, their
      sensitivity to light stimuli. In this study, an investigation is made of the
      effect of different soil moisture conditions during cold-induced dormancy loss on
      changes in the sensitivity of Polygonum aviculare seeds to light. METHODS: Seeds
      buried in pots were stored under different constant and fluctuating soil moisture
      environments at dormancy-releasing temperatures. Seeds were exhumed at regular
      intervals during storage and were exposed to different light treatments. Changes
      in the germination response of seeds to light treatments during storage under the
      different moisture environments were compared in order to determine the effect of
      soil moisture on the sensitivity to light of P. aviculare seeds. KEY RESULTS:
      Seed acquisition of low-fluence responses during dormancy release was not
      affected by either soil moisture fluctuations or different constant soil moisture
      contents. On the contrary, different soil moisture environments affected seed
      acquisition of very low fluence responses and the capacity of seeds to germinate
      in the dark. CONCLUSIONS: The results indicate that under field conditions, the
      sensitivity to light of buried weed seeds could be affected by the soil moisture
      environment experienced during the dormancy release season, and this could affect
      their emergence pattern.

PMID- 17430980
TI  - Seed dispersal by ants in the semi-arid Caatinga of North-East Brazil.
AB  - BACKGROUND AND AIMS: Myrmecochory is a conspicuous feature of several sclerophyll
      ecosystems around the world but it has received little attention in the semi-arid
      areas of South America. This study addresses the importance of seed dispersal by
      ants in a 2500-km(2) area of the Caatinga ecosystem (north-east Brazil) and
      investigates ant-derived benefits to the plant through myrmecochory. METHODS:
      Seed manipulation and dispersal by ants was investigated during a 3-year period
      in the Xingo region. Both plant and ant assemblages involved in seed dispersal
      were described and ant behaviour was characterized. True myrmecochorous seeds of
      seven Euphorbiaceae species (i.e. elaiosome-bearing seeds) were used in
      experiments designed to: (1) quantify the rates of seed cleaning/removal and the
      influence of both seed size and elaiosome presence on seed removal; (2) identify
      the fate of seeds dispersed by ants; and (3) document the benefits of seed
      dispersal by ants in terms of seed germination and seedling growth. KEY RESULTS:
      Seed dispersal by ants involved one-quarter of the woody flora inhabiting the
      Xingo region, but true myrmecochory was restricted to 12.8 % of the woody plant
      species. Myrmecochorous seeds manipulated by ants faced high levels of seed
      removal (38-84 %) and 83 % of removed seeds were discarded on ant nests.
      Moreover, seed removal positively correlated with the presence of elaiosome, and
      elaiosome removal increased germination success by at least 30 %. Finally, some
      Euphorbiaceae species presented both increased germination and seedling growth on
      ant-nest soils. CONCLUSIONS: Myrmecochory is a relevant seed dispersal mode in
      the Caatinga ecosystem, and is particularly frequent among Euphorbiaceae trees
      and shrubs. The fact that seeds reach micro-sites suitable for establishment (ant
      nests) supports the directed dispersal hypothesis as a possible force favouring
      myrmecochory in this ecosystem. Ecosystems with a high frequency of
      myrmecochorous plants appear not to be restricted to regions of nutrient
      impoverished soil or to fire-prone regions.

PMID- 17430981
TI  - Semantic and affective priming as a function of stimulation of the subthalamic
      nucleus in Parkinson's disease.
AB  - Lexical-semantic and emotional processing deficits have been associated with
      Parkinson's disease. This study investigated automatic and controlled lexical
      semantic processing, the automatic activation of emotional evaluations, and the
      processing of words conveying negative and neutral emotional connotations in a
      combined affective and semantic priming paradigm. Eighteen participants with
      Parkinson's disease who had undergone surgery for deep brain stimulation (DBS) of
      the subthalamic nucleus (STN) completed a lexical decision task at short and long
      stimulus onset asynchronies (SOAs), during on and off stimulation conditions.
      Nineteen non-neurologically impaired participants acted as controls. The results
      indicated that automatic lexical-semantic and emotional evaluative processes are
      unimpaired in Parkinson's disease as reflected in the presence of comparable
      semantic and affective priming effects at the short SOA in on and off stimulation
      conditions compared with healthy controls. In contrast, participants with
      Parkinson's disease in the off stimulation condition showed a pattern of aberrant
      controlled lexical-semantic processing as evidenced by a lack of semantic priming
      effects at the long SOA condition. Controlled semantic priming was present,
      however, when the participants with Parkinson's disease were receiving
      stimulation of the STN, suggesting that STN stimulation modulates basal ganglia
      thalamocortical circuits involved in such processes. Finally, delayed reaction
      times for negatively valenced targets compared with neutrally valenced targets
      was evident in participants with Parkinson's disease in the on stimulation
      condition and control participants, but not for participants with Parkinson's
      disease in the off stimulation condition, suggesting that the incidental
      evaluation of negatively versus neutrally valenced words in Parkinson's disease
      is modulated by basal ganglia-thalamocortical circuits.

PMID- 17430982
TI  - FastFISH: technique for ultrarapid fluorescence in situ hybridization on
      uncultured amniocytes yielding results within 2 h of amniocentesis.
AB  - Rapid aneuploidy detection methods allow prenatal diagnosis results to be
      released within 48 h, but not on the same day as the invasive test. We aimed to
      develop a rapid fluorescence in situ hybridization (FISH) method (FastFISH) that
      releases accurate results on the same day as amniocentesis. FastFISH was
      optimized to be completed within 2 h of sample collection using CEP and LSI
      probes for chromosomes 13, 18, 21, X, Y and DiGeorge syndrome (DGS). The
      technique was tested on 100 consecutive amniotic fluid samples in a blinded
      study. It was also validated as a 1-day molecular genetic test on three
      representative fetal tissue samples: chorionic villus, amniotic fluid and fetal
      blood. In the blinded study, FastFISH results were ready within 2 h of sample
      collection. Of the 100 amniotic fluid samples, 49 male and 50 female fetuses were
      identified. One fetus was 47, XXY (Klinefelter syndrome). Three fetuses had
      trisomy 21. One fetus suspected of DGS by ultrasound was identified as normal.
      Results of FastFISH analyses in all 100 cases were concordant with their
      karyotypes (100% accuracy; lower 95% CI, 97.05%). In the 1-day test validation,
      all results were released on the same day and were concordant with their
      respective karyotypes. FastFISH allows results to be released on the same day as
      amniocentesis. It represents the necessary development for a 1-day prenatal
      diagnosis service.

PMID- 17430983
TI  - Characterization of cAMP/PKA/CREB signaling cascade in the bonnet monkey corpus
      luteum: expressions of inhibin-alpha and StAR during different functional status.
AB  - Luteinizing hormone mediates its nuclear action primarily by activating
      cAMP/Protein kinase A (PKA) pathway leading to phosphorylation of cAMP response
      element binding (CREB) family of transcription factors. Earlier studies have
      documented altered cAMP responsiveness of luteal cells during maturation, and in
      the rhesus monkey, extinction of CREB expression following luteinization and
      ovulation. In the course of studies aimed at characterizing LH-cAMP signaling
      pathway, we serendipitously discovered that CREB is after all present in the
      monkey corpus luteum (CL). The present experiments were carried out to examine
      the PKA activity, CREB expression and RT-PCR expression of inhibin-alpha (Inh
      alpha) subunit and steroidogenic acute regulatory protein (StAR) in CL obtained
      from a variety of model systems. PKA activity in the CL was maintained throughout
      the luteal phase. Messenger RNA expression by RT-PCR and Northern analyses and
      protein levels employing antibodies specific to total- and phospho-forms
      demonstrated presence of CREB in the CL. Additionally, immuno-histo/cytochemical
      analyses, Electrophoretic mobility shift assays and chromatin immunoprecipitation
      assays for Inh-alpha and StAR genes further confirmed the presence of CREB in the
      CL. The present study, contrary to an earlier report, demonstrates the presence
      of CREB (both transcript and protein) in the monkey CL. Also, analysis of
      expression of Inh-alpha and StAR genes (considered to be cAMP responsive), during
      different functional status of CL suggests that LH regulates their expression
      perhaps by cAMP/PKA/CREB pathway.

PMID- 17430984
TI  - Leukaemia inhibitory factor receptor and gp130 in the human Fallopian tube and
      endometrium before and after mifepristone treatment and in the human
      preimplantation embryo.
AB  - Leukaemia inhibitory factor (LIF) is a cytokine, which is associated with
      reproductive processes such as embryo development and implantation. The
      objectives of this study were to detect the presence of LIF receptor (LIFR) and
      glycoprotein 130 (gp 130) in the human Fallopian tube, endometrium and
      preimplantation embryo and to study the effect of mifepristone on the expression
      of LIFR and gp130 in the Fallopian tube. Twenty-two healthy fertile women
      received a single dose of 200 mg mifepristone or placebo immediately after
      ovulation (LH + 2). Biopsies were obtained from the Fallopian tubes during
      laparoscopic sterilization once between days LH + 4 and LH + 6 and from
      endometrium once between days LH + 6 and LH + 8. Preimplantation embryos were
      received from couples undergoing in vitro fertilization treatment.
      Immunohistochemistry was used to detect the presence of LIFR and gp130 in the
      Fallopian tube, endometrium and preimplantation embryo. Real-time PCR was used to
      study LIFR and gp130 expression in the Fallopian tube and endometrium. LIFR and
      gp130 were localized in the Fallopian tube, preimplantation embryo and
      endometrium. LIFR was more abundant in the Fallopian tube than in the
      endometrium. In the blastocyst, the staining of gp130 was mainly localized in the
      inner cell mass, whereas LIFR was expressed in all cells. The presence of LIFR
      and gp130 in the Fallopian tube and preimplantation embryo indicates a role for
      LIF in communication between the embryo and the Fallopian tube. Mifepristone did
      not affect the expression of LIFR and gp130 in the Fallopian tube, nor in the
      endometrium suggesting that progesterone might not be directly involved in the
      regulation of LIFR or gp130.

PMID- 17430985
TI  - The application of eye-tracking technology in the study of autism.
AB  - For many decades, eye-tracking has been used to investigate gaze behaviour in the
      normal population. Recent studies have extended its use to individuals with
      disorders on the autism spectrum. Such studies typically focus on the processing
      of socially salient stimuli. In this review, we discuss the potential for this
      technique to reveal the strategies adopted by individuals with high-functioning
      autism when processing social information. Studies suggest that eye-tracking
      techniques have the potential to offer insight into the downstream difficulties
      in everyday social interaction which such individuals experience.

PMID- 17430986
TI  - Motor and sensory re-innervation of the lung and heart after re-anastomosis of
      the cervical vagus nerve in rats.
AB  - There is no study in the literature dealing with re-innervation of the
      cardiopulmonary vagus nerve after its transection followed by re-anastomosis. In
      the present study, we explored the bronchomotor, heart rate and respiratory
      responses in rats at 2, 3 and 6 months after re-anastomosis of one cervical vagus
      trunk. The conduction velocity of A, B and C waves was calculated in the compound
      vagal action potential. We searched for afferent vagal activities in phase with
      pulmonary inflation to assess the persistence of pulmonary stretch receptor (PSR)
      discharge in re-innervated lungs. In each animal, data from the stimulation or
      recording of one re-anastomosed vagus nerve were compared with those obtained in
      the contra-lateral intact one. Two and three months after surgery, the conduction
      velocities of A and B waves decreased, but recovery of conduction velocity was
      complete at 6 months. By contrast, the conduction velocity of the C wave did not
      change until 6 months, when it was doubled. The PSR activity was present in 50%
      of re-anastomosed vagus nerves at 2 and 3 months and in 75% at 6 months.
      Respiratory inhibition evoked by vagal stimulation was significantly weaker from
      the re-anastomosed than intact nerve at 2 but not 3 months. Vagal stimulation did
      not elicit cardiac slowing or bronchoconstriction 6 months after re-anastomosis.
      Our study demonstrates the capacity of pulmonary vagal sensory neurones to
      regenerate after axotomy followed by re-anastomosis, and the failure of the vagal
      efferents to re-innervate both the lungs and heart.

PMID- 17430987
TI  - Independent vasomotor control of rat tail and proximal hairy skin.
AB  - Quantitative differences are known to exist between the vasomotor control of
      hairy and hairless skin, but it is unknown whether they are regulated by common
      central mechanisms. We made simultaneous recordings from sympathetic cutaneous
      vasoconstrictor (CVC-type) fibres supplying back skin (hairy) and tail (hairless)
      in urethane-anaesthetized, artificially ventilated rats. The animal's trunk was
      shaved and encased in a water-perfused jacket. Both tail and back skin CVC-type
      fibres were activated by cooling the trunk skin, and independently by the
      resultant fall in core (rectal) temperature, but their thresholds for activation
      differed (skin temperatures 38.8 +/- 0.4 degrees C versus 36.8 +/- 0.4 degrees C,
      core temperatures 38.1 +/- 0.2 degrees C versus 36.8 +/- 0.2 degrees C,
      respectively; P < 0.01). Back skin CVC-type fibres were more responsive to skin
      than to core cooling, while the reverse applied to tail fibres. Back skin CVC
      type fibres were less responsive than tail fibres to prostaglandin E2 (PGE2)
      microinjected into the preoptic area. Spectral analysis showed no significant
      coherence between tail and back skin CVC-type fibre activities during cooling.
      After preoptic PGE2 injection, a coherent peak at 1 Hz appeared in some animals;
      this disappeared after partialization with respect to ventilatory pressure,
      indicating that it was attributable to common ventilatory modulation. Neuronal
      inhibition in the rostral medullary raphe by microinjected muscimol (2 mM, 60-120
      nl) suppressed both tail and back skin CVC-type fibre activities, and prevented
      their responses to subsequent skin cooling. These results indicate that
      thermoregulatory responses of hairless and hairy skin vessels are controlled by
      independent neural pathways, although both depend on synaptic relays in the
      medullary raphe.

PMID- 17430988
TI  - Brief hyperglycaemia in the early pregnant rat increases fetal weight at term by
      stimulating placental growth and affecting placental nutrient transport.
AB  - In pregnant women with type 1 diabetes, suboptimal glucose control in the first
      trimester is a strong predictor for giving birth to a large fetus. However, the
      mechanisms underlying this association are unknown. We hypothesized that
      transient hyperglycaemia in early pregnancy results in (1) increased placental
      growth and (2) an up-regulation of placental nutrient transport capacity, which
      leads to fetal overgrowth at term. In order to test this hypothesis, pregnant
      rats were given intraperitoneal injections of glucose (2 g kg(-1), resulting in a
      50-100% increase in blood glucose level during 90 min) or saline (control) in
      either early or late gestation using four different protocols: one single
      injection on gestational day (GD) 10 (n=5), three injections on GD 10 (n=8-9),
      six injections on GD 10 and 11 (n=9-11) or three injections on GD 19 (n=7-8).
      Multiple injections were given approximately 4 h apart. Subsequently, animals
      were studied on GD 21. Three glucose injections in early pregnancy significantly
      increased placental weight by 10%, whereas fetal weight was found to be increased
      at term in response to both three (9% increase in fetal weight, P<0.05) and six
      glucose injections (7%, P=0.05) in early gestation. A single glucose injection on
      GD 10 or three injections of glucose on GD 19 had no effect on placental or fetal
      growth. In groups where a change in feto-placental growth was observed, we
      measured placental system A and glucose transport activity in the awake animals
      on GD 21 and placental expression of the glucose and amino acid transporters
      GLUT1, GLUT3, SNAT2 (system A), LAT1 and LAT 2 (system L). Placental system A
      transport at term was down-regulated by six glucose injections in early pregnancy
      (by -33%, P<0.05), whereas placental mRNA and protein levels were unchanged. No
      long-term alterations in maternal metabolic status were detected. In conclusion,
      we demonstrate that transient hyperglycaemia in early pregnancy is sufficient to
      increase fetal weight close to term. In contrast, brief hyperglycaemia in late
      pregnancy did not stimulate fetal growth. Increased fetal growth may be explained
      by a larger placenta, which would allow for more nutrients to be transferred to
      the fetus. These data suggest that maternal metabolic control in early pregnancy
      is an important determinant for feto-placental growth and placental function
      throughout the remainder of gestation. We speculate that maternal metabolism in
      early pregnancy represents a key environmental cue to which the placenta responds
      in order to match fetal growth rate with the available resources of the mother.

PMID- 17430989
TI  - Oestrogen affects the cardiovascular and central responses to isoproterenol of
      female rats.
AB  - This study examined the influence of oestrogen on cardiovascular responses to
      hypotension produced by administration of isoproterenol (Isop) and on neural
      activation in hindbrain nuclei mediating these responses. We first measured mean
      arterial pressure (MAP) and heart rate (HR) after administration of
      isoproterenol, a beta-adrenergic agonist that increases circulating levels of
      AngII, in ovariectomized (OVX) rats treated with oestradiol benzoate (EB). We
      then evaluated EB effects on Isop-induced Fos immunoreactivity (Fos-IR) in the
      hindbrain baroreflex circuit. To control for weight loss associated with
      oestrogen replacement in OVX rats, we food restricted a separate group of OVX
      rats and evaluated Isop-induced changes in MAP, HR and Fos-IR. The depressor
      response to Isop was significantly attenuated by EB, which also produced a
      disproportionate increase in HR. These effects were not secondary to loss of body
      weight after EB treatment, because cardiovascular responses to Isop in food
      restricted rats were similar to those in OVX rats treated with the oil vehicle.
      Isop significantly increased Fos-IR in the nucleus of the solitary tract (NTS),
      area postrema (AP), rostral ventrolateral medulla (RVLM), and lateral
      parabrachial nucleus (lPBN); however, EB significantly attenuated the increase in
      the AP and in the lPBN. Again, these effects were not secondary to body weight
      loss, because food restricted rats had the same pattern of Fos-IR as did rats
      treated with the oil vehicle. These results suggest that EB modifies
      cardiovascular responses to Isop, possibly by decreasing activation of the AP and
      lPBN.

PMID- 17430990
TI  - beta-Liddle mutation of the epithelial sodium channel increases alveolar fluid
      clearance and reduces the severity of hydrostatic pulmonary oedema in mice.
AB  - Transepithelial sodium transport via alveolar epithelial Na(+) channels and
      Na(+),K(+)-ATPase constitutes the driving force for removal of alveolar oedema
      fluid. Decreased activity of the amiloride-sensitive epithelial Na(+) channel
      (ENaC) in the apical membrane of alveolar epithelial cells impairs sodium-driven
      alveolar fluid clearance (AFC) and predisposes to pulmonary oedema. We
      hypothesized that hyperactivity of ENaC in the distal lung could improve AFC and
      facilitate the resolution of pulmonary oedema. AFC and lung fluid balance were
      studied at baseline and under conditions of hydrostatic pulmonary oedema in the
      beta-Liddle (L) mouse strain harbouring a gain-of-function mutation
      (R(566)(stop)) within the Scnn1b gene. As compared with wild-type (+/+), baseline
      AFC was increased by 2- and 3-fold in heterozygous (+/L) and homozygous mutated
      (L/L) mice, respectively, mainly due to increased amiloride-sensitive AFC. The
      beta(2)-agonist terbutaline stimulated AFC in +/+ and +/L mice, but not in L/L
      mice. Acute volume overload induced by saline infusion (40% of body weight over 2
      h) significantly increased extravascular (i.e. interstitial and alveolar) lung
      water as assessed by the bloodless wet-to-dry lung weight ratio in +/+ and L/L
      mice, as compared with baseline. However, the increase was significantly larger
      in +/+ than in L/L groups (P=0.01). Volume overload also increased the volume of
      the alveolar epithelial lining fluid in +/+ mice, indicating the presence of
      alveolar oedema, but not in L/L mice. Cardiac function as evaluated by
      echocardiography was comparable in both groups. These data show that constitutive
      ENaC activation improved sodium-driven AFC in the mouse lung, and attenuated the
      severity of hydrostatic pulmonary oedema.

PMID- 17430991
TI  - Effects of a R133W beta-tropomyosin mutation on regulation of muscle contraction
      in single human muscle fibres.
AB  - A novel R133W beta-tropomyosin (beta-Tm) mutation, associated with muscle
      weakness and distal limb deformities, has recently been identified in a woman and
      her daughter. The muscle weakness was not accompanied by progressive muscle
      wasting or histopathological abnormalities in tibialis anterior muscle biopsy
      specimens. The aim of the present study was to explore the mechanisms underlying
      the impaired muscle function in patients with the beta-Tm mutation. Maximum force
      normalized to fibre cross-sectional area (specific force, SF), maximum velocity
      of unloaded shortening (V0), apparent rate constant of force redevelopment (ktr)
      and force-pCa relationship were evaluated in single chemically skinned muscle
      fibres from the two patients carrying the beta-Tm mutation and from healthy
      control subjects. Significant differences in regulation of muscle contraction
      were observed in the type I fibres: a lower SF (P<0.05) and ktr (P<0.01), and a
      faster V0 (P<0.05). The force-pCa relationship did not differ between patient and
      control fibres, indicating an unaltered Ca2+ activation of contractile proteins.
      Collectively, these results indicate a slower cross-bridge attachment rate and a
      faster detachment rate caused by the R133W beta-Tm mutation. It is suggested that
      the R133W beta-Tm mutation induces alteration in myosin-actin kinetics causing a
      reduced number of myosin molecules in the strong actin-binding state, resulting
      in overall muscle weakness in the absence of muscle wasting.

PMID- 17430993
TI  - A Nav1.7 channel mutation associated with hereditary erythromelalgia contributes
      to neuronal hyperexcitability and displays reduced lidocaine sensitivity.
AB  - Mutations in the TTX-sensitive voltage-gated sodium channel subtype Nav1.7 have
      been implicated in the painful inherited neuropathy, hereditary erythromelalgia.
      Hereditary erythromelalgia can be difficult to treat and, although sodium
      channels are targeted by local anaesthetics such as lidocaine (lignocaine), some
      patients do not respond to treatment with local anaesthetics. This study examined
      electrophysiological differences in Nav1.7 caused by a hereditary erythromelalgia
      mutation (N395K) that lies within the local anaesthetic binding site of the
      channel. The N395K mutation produced a hyperpolarized voltage dependence of
      activation, slower kinetics of deactivation, and impaired steady-state slow
      inactivation. Computer simulations indicate that the shift in activation is the
      major determinant of the hyperexcitability induced by erythromelalgia mutations
      in sensory neurons, but that changes in slow inactivation can modulate the
      overall impact on excitability. This study also investigated lidocaine inhibition
      of the Nav1.7-N395K channel. We show that the N395K mutation attenuates the
      inhibitory effects of lidocaine on both resting and inactivated Nav1.7. The IC50
      for lidocaine was estimated at 500 microM for inactivated wild-type Nav1.7 and
      2.8 mM for inactivated Nav1.7-N395K. The N395K mutation also significantly
      reduced use-dependent inhibition of lidocaine on Nav1.7 current. In contrast, a
      different hereditary erythromelalgia mutation (F216S), not located in the local
      anaesthetic binding site, had no effect on lidocaine inhibition of Nav1.7
      current. Our observation of reduced lidocaine inhibition on Nav1.7-N395K shows
      that the residue N395 is critical for lidocaine binding to Nav1.7 and suggests
      that the response of individuals with hereditary erythromelalgia to lidocaine
      treatment may be determined, at least in part, by their specific genotype.

PMID- 17430994
TI  - Receptor-mediated activation of heterotrimeric G-proteins: current structural
      insights.
AB  - G-protein-coupled receptors (GPCRs) serve as catalytic activators of
      heterotrimeric G-proteins (Galphabetagamma) by exchanging GTP for the bound GDP
      on the Galpha subunit. This guanine nucleotide exchange factor activity of GPCRs
      is the initial step in the G-protein cycle and determines the onset of various
      intracellular signaling pathways that govern critical physiological responses to
      extracellular cues. Although the structural basis for many steps in the G-protein
      nucleotide cycle have been made clear over the past decade, the precise mechanism
      for receptor-mediated G-protein activation remains incompletely defined. Given
      that these receptors have historically represented a set of rich drug targets, a
      more complete understanding of their mechanism of action should provide further
      avenues for drug discovery. Several models have been proposed to explain the
      communication between activated GPCRs and Galphabetagamma leading to the
      structural changes required for guanine nucleotide exchange. This review is
      focused on the structural biology of G-protein signal transduction with an
      emphasis on the current hypotheses regarding Galphabetagamma activation. We
      highlight several recent results shedding new light on the structural changes in
      Galpha that may underlie GDP release.

PMID- 17430992
TI  - Light triggers expression of philanthotoxin-insensitive Ca2+-permeable AMPA
      receptors in the developing rat retina.
AB  - Ca2+-permeable AMPA receptors (AMPARs) are expressed throughout the adult CNS but
      yet their role in development is poorly understood. In the developing retina,
      most investigations have focused on Ca2+ influx through NMDARs in promoting
      synapse maturation and not on AMPARs. However, NMDARs are absent from many
      retinal cells suggesting that other Ca2+-permeable glutamate receptors may be
      important to consider. Here we show that inhibitory horizontal and AII amacrine
      cells lack NMDARs but express Ca2+-permeable AMPARs. Before eye-opening, AMPARs
      were fully blocked by philanthotoxin (PhTX), a selective antagonist of Ca2+
      permeable AMPARs. After eye-opening, however, a subpopulation of Ca2+-permeable
      AMPARs were unexpectedly PhTX resistant. Furthermore, Joro spider toxin (JSTX)
      and IEM-1460 also failed to antagonize, demonstrating that this novel
      pharmacology is shared by several AMPAR channel blockers. Interestingly, PhTX
      insensitive AMPARs failed to express in retinae from dark-reared animals
      demonstrating that light entering the eye triggers their expression. Eye-opening
      coincides with the consolidation of inhibitory cell connections suggesting that
      the developmental switch to a Ca2+-permeable AMPAR with novel pharmacology may be
      critical to synapse maturation in the mammalian retina.

PMID- 17430995
TI  - Vasoactive intestinal peptide transactivates the androgen receptor through a
      protein kinase A-dependent extracellular signal-regulated kinase pathway in
      prostate cancer LNCaP cells.
AB  - Acquisition of androgen independence by prostate cancer is the key problem of
      prostate cancer progression. Vasoactive intestinal peptide (VIP), a neuropeptide,
      may act as a survival factor for prostate cancer cells under androgen
      deprivation. However, the molecular mechanisms by which VIP promotes the androgen
      independent growth of androgen-sensitive prostate cancer cells have not been
      addressed. We therefore investigated the biological effect and signal pathway of
      VIP in LNCaP cells, a prostate cancer cell line that requires androgens for
      growth. We showed that low nanomolar concentrations of VIP, acting through G(s)
      protein-coupled VIP receptors, can induce LNCaP cell growth in the absence of
      androgen. Blockade of androgen-receptor (AR) in these cells by AR antagonist
      bicalutamide or by anti-AR small interfering RNA, inhibited the proliferative
      effect of VIP. In addition, VIP stimulated androgen-independent activation of AR
      with an EC(50) of 3.0 +/- 0.8 nM. We then investigated VIP-stimulated signaling
      events that may interact with the AR pathway in prostate cancer cells. VIP
      regulation of AR activation, mediated by VIP receptors, was protein kinase A
      (PKA)-dependent, and extracellular signal-regulated kinase 1/2 (ERK1/2)
      activation contributes to VIP-mediated AR activation. Furthermore, PKA-dependent
      Rap1 activation is required for both ERK1/2 activation and androgen-independent
      AR activation in LNCaP cells upon VIP stimulation. Finally, we showed that VIP
      induced AR activation was also present in prostate cancer CWR22Rv1 and PC3 cells
      transfected with the wild-type AR. Altogether, we demonstrate that VIP acting
      through its G(s)-protein-coupled receptors can cause androgen-independent
      transactivation of AR through a PKA/Rap1/ERK1/2 pathway, thus promoting androgen
      independent proliferation of androgen-sensitive prostate cancer cells.

PMID- 17430996
TI  - Left ventricular dyssynchrony and functional mitral regurgitation: two dynamic
      conditions.

PMID- 17430997
TI  - Vascular abnormalities in primary amyloidosis.
AB  - AIMS: Primary amyloidosis (AL) is a systemic disease; however, there is limited
      information regarding the presence and character of vascular abnormalities.
      METHODS AND RESULTS: Validated ultrasound techniques were used to prospectively
      determine carotid artery intimal-medial thickness (IMT) and brachial artery flow
      mediated dilatation (FMD) in 59 consecutive AL patients and 17 age-similar,
      healthy, asymptomatic volunteers (CON). Carotid IMT was increased in AL when
      compared with CON (0.07 +/- 0.02 vs. 0.04 +/- 0.01 mm, P < 0.01). Similarly,
      brachial artery FMD was significantly lower in AL when compared with CON subjects
      (3 +/- 7 vs. 12 +/- 8%, P < 0.01). Multivariable analysis revealed that AL was
      associated with larger IMT and lower FMD after controlling for several
      confounding variables. However, within AL cases, there was not a significant
      association of cardiac vs. non-cardiac involvement with IMT or FMD (P = 0.1 and
      0.2, respectively). CONCLUSION: AL is associated with abnormal vascular
      morphology and endothelial dysfunction. Vascular abnormalities do not appear to
      be related to echocardiographic evidence of cardiac involvement.

PMID- 17430998
TI  - Stroke prevention in atrial fibrillation: antiplatelet therapy revisited.

PMID- 17430999
TI  - Hyponatraemia in heart failure: a call for redefinition.

PMID- 17431000
TI  - Impact of aspirin with or without clopidogrel on postoperative bleeding and blood
      transfusion in coronary surgical patients treated prophylactically with a low
      dose of aprotinin.
AB  - AIMS: Aspirin combined with clopidogrel is the treatment of choice for acute
      coronary syndromes. Although the maintenance of aspirin until surgery does not
      affect postoperative bleeding after coronary artery bypass graft (CABG) surgery,
      the latter may be dramatically increased when clopidogrel is continued over a
      period of 5 days preoperatively. METHODS AND RESULTS: This prospective
      observational study included 217 consecutive patients scheduled for first-time
      CABG. Postoperative bleeding and blood transfusion requirements were compared
      (equivalence) between patients pretreated during a period of 5 days prior surgery
      by either aspirin alone (n = 157) or combined with clopidogrel (n = 60).
      Aprotinin was systematically used in all these patients considered as high risk
      for bleeding. We found no significant difference between both groups concerning
      the preoperative characteristics except for unstable angina (33 vs. 19%, P =
      0.02) and left main coronary artery stenosis (27 vs. 13%, P = 0.02), which were
      more frequent in patients receiving clopidogrel. The median chest tube output was
      similar in both groups 24 h postoperatively at 350 mL (95% CI 150-850) vs. 375 mL
      (95% CI 175-875), and the difference between groups (7%, 95% CI -9 to 22) did not
      encompass the predetermined margins of equivalence (25%). No significant
      difference was found on blood transfusion use (38 vs. 38%, P = 0.99). After
      adjustment by a propensity score, we found that clopidogrel was not associated
      with an increased risk of excessive bleeding. CONCLUSION: In patients undergoing
      first-time CABG and treated prophylactically with aprotinin, aspirin and
      clopidogrel may be continued until surgery without increasing postoperative
      bleeding or transfusion requirements.

PMID- 17431001
TI  - Pulmonary artery aneurysm due to systemic vasculitis: assessment of vascular
      inflammation using F-18 FDG positron emission tomography.

PMID- 17431002
TI  - Opposite effects of leptin on bone metabolism: a dose-dependent balance related
      to energy intake and insulin-like growth factor-I pathway.
AB  - Published data describing leptin effects on bone are at variance with both
      positive and negative consequences reported. These findings are consistent with a
      bimodal threshold response to serum leptin levels. To test this theory, two
      groups of female rats (tail-suspended and unsuspended) were treated with ip
      leptin at two different doses or vehicle for 14 d. In tail-suspended rats, low
      dose leptin compensated the decrease in serum leptin levels observed with
      suspension and was able to prevent the induced bone loss at both the trabecular
      and cortical level (assessed by three-dimensional microtomography). In contrast,
      high-dose leptin inhibited femoral bone growth and reduced bone mass by
      decreasing bone formation rate and increasing bone resorption in both tail
      suspended and unsuspended groups. High- and low-dose leptin administration
      resulted in a reduced medullar adipocytic volume in all groups. High-dose leptin
      (but not low) induced a decrease in body-weight abdominal fat mass and serum IGF
      I levels. Thus, the observed bone changes at high-dose leptin are at least partly
      mediated by a leptin-induced energy imbalance. In conclusion, a balance between
      negative and positive leptin effects on bone is dependent on a bimodal threshold
      that is triggered by leptin serum concentration. Also, the negative effects of
      high leptin levels are likely induced by reduced energy intake and related
      hormonal changes. The respective part of each pathway will be unraveled by
      additional studies.

PMID- 17431003
TI  - Different induction of GRP78 and CHOP as a predictor of sensitivity to proteasome
      inhibitors in thyroid cancer cells.
AB  - Proteasome inhibitors represent a novel class of antitumor agents with
      preclinical and clinical evidence of activity against hematological malignancies
      and solid tumors. Emerging lines of evidence suggest that the unfolded protein
      response is implicated in proteasome inhibitors-induced apoptosis. Glucose
      regulated protein 78 kDa (GRP78) and CCAAT/enhancer-binding protein homologous
      protein (CHOP) as part of the unfolded protein response play critical roles in
      cell survival or death. Here we demonstrate that induction of GRP78 and CHOP are
      differently regulated upon proteasome inhibition in different thyroid cancer cell
      lines, and GRP78 levels as well as preferential induction of GRP78 or CHOP
      appears to be involved in the responsiveness. Insensitive ARO, 8305C, and 8505C
      cell lines inherently express relatively high levels of GRP78 compared with
      sensitive cell lines, and its levels are further up-regulated upon treatment with
      proteasome inhibitors. CHOP levels are dramatically induced in sensitive cell
      lines until 24 h after proteasome inhibition. On the other hand, only a slight
      increase is observed at 4 h in insensitive cell lines, and this increase is
      unable to be detected after 8 h. Insensitive cells are sensitized to proteasome
      inhibition by suppression of GRP78. Furthermore, suppression of CHOP induction or
      overexpression of GRP78 partially prevents proteasome inhibition-mediated cell
      death. Our study indicates a molecular mechanism by which the sensitivity of
      thyroid cancer cells is regulated by the level of GRP78 as well as preferential
      induction of GRP78 or CHOP upon treatment with proteasome inhibitors. Our
      experiments therefore suggest a novel approach toward sensitization of thyroid
      cancer cells to proteasome inhibitors.

PMID- 17431004
TI  - WNTs in the ovine uterus: potential regulation of periimplantation ovine
      conceptus development.
AB  - WNTs (Wingless-type MMTV integration site family member) are involved in critical
      developmental and growth processes in animals. These studies investigated WNT
      pathways in the ovine uterus and conceptus during the periimplantation period of
      pregnancy. WNT2 and WNT2B mRNAs were detected in endometrial stroma. WNT5A and
      WNT5B mRNAs were most abundant in the stroma and less so in the luminal
      epithelium, whereas WNT11 mRNA was detected primarily in the glands. WNT7A mRNA
      was present in the luminal epithelium on d 10, absent on d 12 and 14, and
      increased between d 16 and 20. Only WNT2, WNT2B, and WNT4 were detected in
      conceptus trophectoderm. FZD6/8 (frizzled receptor) and GSK3B (glycogen synthase
      kinase 3beta) mRNAs were detected primarily in endometrial epithelia and
      conceptus trophectoderm, whereas the LRP5/6 (low-density lipoprotein receptor
      related proteins 5 and 6) coreceptor was present in all endometrial cells and the
      trophectoderm. DKK1 (Dickkopf), a WNT signaling inhibitor, increased in the
      endometrium from d 16-20. CTNNB1 [catenin (cadherin associated protein) beta1]
      and CDH1 (E-cadherin) mRNAs were most abundant in the endometrial epithelia and
      trophectoderm. LEF1 (lymphoid enhancer-binding factor 1) mRNA was expressed
      primarily in uterine epithelia, whereas TCF7L2 [(transcription factor 7-like 2 (T
      cell specific, HMG-box)] was primarily in the conceptus. CTNNB1 and TCF7L2
      proteins were both abundant in the nuclei of trophoblast giant binucleate cells.
      WNT7A stimulated a TCF/LEF-luciferase reporter activity in ovine trophectoderm
      cells that was inhibited by dominant-negative TCF and Sfrp2 (secreted FZD-related
      protein 2). WNT7A increased trophectoderm cell proliferation as well as MSX2 (msh
      homeobox 2) and MYC (myelocytomatosis oncogene) mRNA levels. Wnt5a increased
      trophectoderm cell migration in a Rho kinase-dependent manner. These results
      support the hypotheses that canonical and noncanonical WNT signaling pathways are
      conserved regulators of conceptus-endometrial interactions in mammals and
      regulate periimplantation ovine conceptus development.

PMID- 17431005
TI  - The onset of labor alters corticotropin-releasing hormone type 1 receptor variant
      expression in human myometrium: putative role of interleukin-1beta.
AB  - CRH targets the human myometrium during pregnancy. The efficiency of CRH actions
      is determined by expression of functional receptors (CRH-R), which are
      dynamically regulated. Studies in myometrial tissue biopsies using quantitative
      RT-PCR demonstrated that the onset of labor, term or preterm, is associated with
      a significant 2- to 3-fold increase in CRH-R1 mRNA levels. Detailed analysis of
      myometrial CRH-R1 mRNA variants showed a decline of the pro-CRH-R1 mRNA encoding
      the CRH-R1beta variant during labor and increased mRNA levels of CRH-R1d mRNA.
      Studies in myometrial cells identified IL-1beta as an important regulator of
      myometrial CRH-R1 gene expression because prolonged treatment of myometrial cells
      with IL-1beta (1 ng/ml) for 18 h induced expression of CRH-R1 mRNA levels by 1.5-
      to 2-fold but significantly attenuated CRH-R1beta mRNA expression by 70%. In
      contrast, IL-1beta had no effect on CRH-R1d mRNA expression. Studies using
      specific inhibitors suggest that ERK1/2, p38 MAPK, and downstream nuclear
      translocation of nuclear factor-kappaB mediate IL-1beta effects on myometrial CRH
      R1 gene. However, the increased CRH-R1 mRNA expression was associated with a
      dampening of the receptor efficacy to activate the adenylyl cyclase/cAMP
      signaling cascade. Thus, our findings suggest that IL-1beta is an important
      regulator of CRH-R1 expression and functional activity, and this interaction
      might play a role in the transition of the uterus from quiescence to active
      contractions necessary for the onset of parturition.

PMID- 17431006
TI  - Circadian clock gene regulation of steroidogenic acute regulatory protein gene
      expression in preovulatory ovarian follicles.
AB  - It is now known that circadian clocks are localized not only in the central
      pacemaker but also in peripheral organs. An example of a clock-dependent
      peripheral organ is the ovary of domestic poultry in which ovulation is induced
      by the positive feedback action of ovarian progesterone on the neuroendocrine
      system to generate a preovulatory release of LH during a daily 6-10 h "open
      period" of the ovulatory cycle. It has been assumed previously that the timing of
      ovulation in poultry is controlled solely by a clock-dependent mechanism within
      the neuroendocrine system. Here, we question this assumption by demonstrating the
      expression of the clock genes, Per2 (Period 2) and Per3, Clock, and Bmal1 (brain
      and muscle Arnt-like protein 1), in preovulatory follicles in laying quail.
      Diurnal changes in Per2 and Per3 expression were seen in the largest preovulatory
      follicle (F1) but not in smaller follicles. We next sought to identify clock
      driven genes in preovulatory follicles focusing on those involved in the
      synthesis of progesterone. One such gene was identified, encoding steroidogenic
      acute regulatory protein (StAR), which showed 24-h changes in expression in the
      F1 follicle coinciding with those of Per2. Evidence that StAR gene expression is
      clock driven was obtained by showing that its 5' flanking region contains E-box
      enhancers that bind to CLOCK/BMAL1 heterodimers to activate gene transcription.
      We also showed that LH administration increased the promoter activity of chicken
      StAR. We therefore suggest that the timing of ovulation in poultry involves an LH
      responsive F1 follicular clock that is involved in the timing of the preovulatory
      release of progesterone.

PMID- 17431007
TI  - Ovarian epithelial inclusion cysts in chronically superovulated CD1 and Smad2
      dominant-negative mice.
AB  - Chronic ovulation as a contributing factor for the development of epithelial
      ovarian cancer in women has long been an outstanding hypothesis. To test the
      incessant ovulation hypothesis, mice were superovulated using weekly ip
      injections of pregnant mare serum gonadotropin (5 IU/animal), followed 48 h later
      by human chorionic gonadotropin (5 IU/animal). Wild-type CD1 mice were used along
      with CD1 mice expressing a Smad2 dominant-negative (Smad2DN) transgene under the
      control of the Mullerian inhibiting substance promoter that targets expression to
      the ovary and enhances cyst formation. After chronic injections, ovaries were
      analyzed from animals 6 months of age for the total adjusted number of cysts,
      cyst area, cyst location, and key signaling pathways. All observed cysts were
      confirmed to be of epithelial origin. The number of cysts was not significantly
      different between superovulated and control mice in either the wild-type or
      Smad2DN groups. However, the combination of the Smad2DN transgene and
      superovulation resulted in an increase in cyst formation compared with normal
      littermates that were unstimulated. Rapid proliferation of the cells lining the
      cysts was detected using bromodeoxyuridine and phospho-histone 3
      immunohistochemistry but was not different in the ovarian surface epithelium or
      in the cyst lining between groups. These data suggest that chronic superovulation
      in Smad2DN mice results in a higher incidence of cyst formation compared with
      unstimulated controls, but the epithelial lined cysts did not progress to cancer
      over the course of this study.

PMID- 17431008
TI  - The critical time window for androgen-dependent development of the Wolffian duct
      in the rat.
AB  - Androgens are thought to separately regulate stabilization and differentiation of
      the Wolffian duct (WD), but the time windows for these effects are unclear. To
      address this, fetal rats were exposed to flutamide within either an early window
      (EW) [embryonic day 15.5 (E15.5) to E17.5], when the WD degenerates in the
      female, or a later window (LW) (E19.5-E21.5), when the WD morphologically
      differentiates in the male, or during the full window of WD development (FW)
      (E15.5-21.5). WDs were examined for abnormalities during fetal (E21.5) or
      postnatal life, and anogenital distance and prostate presence/absence were
      recorded. Exposure to FW- or EW-flutamide, but not to LW-flutamide, induced
      comparable abnormalities in the fetal WD at E21.5, namely reduced WD coiling,
      reduced cell proliferation, reduced epithelial cell height, altered epithelial
      vimentin expression, and reduced expression of smooth muscle actin in the WD
      inner stroma. Exposure to EW- or FW-flutamide, but not to LW-flutamide, resulted
      in incomplete/absent WDs in more than 50% of males by adulthood, although such
      abnormalities were infrequent in fetal life. These findings suggest that androgen
      action during the EW is sufficient to promote WD morphological differentiation
      several days later. Because the androgen receptor is expressed in the WD stroma
      but not in the epithelium during this EW, WD differentiation is likely to be
      dependent on androgen-mediated signaling from the stroma to the epithelium. In
      conclusion, the critical window for androgen action in regulating WD development
      in the rat is between E15.5 and E17.5. This window is also important for prostate
      formation and anogenital distance masculinization.

PMID- 17431009
TI  - Insulin protects liver cells from saturated fatty acid-induced apoptosis via
      inhibition of c-Jun NH2 terminal kinase activity.
AB  - Hepatocyte apoptosis is increased in patients with nonalcoholic steatohepatitis
      and correlates with disease severity. Long-chain saturated fatty acids, such as
      palmitate and stearate, induce apoptosis in liver cells. The present study
      examined insulin-mediated protection against saturated fatty acid-induced
      apoptosis in the rat hepatoma cell line, H4IIE, and primary rat hepatocytes.
      Cells were provided a control media (no fatty acids) or the same media containing
      250 micromol/liter of albumin-bound oleate or palmitate for 16 h. Insulin
      concentrations were 0, 1, 10, or 100 nmol/liter (n=4-6/treatment). Palmitate, but
      not oleate, activated caspase-3 and induced DNA fragmentation in the absence of
      insulin. Insulin reduced palmitate-mediated activation of caspase-3 and DNA
      fragmentation in a dose-dependent manner. Phosphatidylinositol 3-kinase
      inhibitors abolished these effects of insulin. Insulin-mediated inhibition of
      palmitate-induced apoptosis was not due to an augmentation in the unfolded
      protein response or increased expression of genes encoding the inhibitor of
      apoptosis proteins, inhibitor of apoptosis protein-2 and X-linked mammalian
      inhibitor of apoptosis protein. Palmitate, but not oleate, increased c-Jun NH2
      terminal kinase activity in the absence of insulin. Insulin or SP600125, a
      chemical inhibitor of c-Jun NH2 terminal kinase, blocked palmitate-mediated
      activation of c-Jun NH2 terminal kinase and reduced apoptosis. These data suggest
      that insulin is an important determinant of saturated fatty acid-induced
      apoptosis in liver cells and may have implications for fatty acid-mediated liver
      cell injury in insulin-deficient and/or -resistant states.

PMID- 17431011
TI  - Invited commentary: when bad genes look good - APOE*E4, cognitive decline, and
      diagnostic thresholds.
AB  - Scientific interest frequently focuses on how factors that influence disease
      onset subsequently affect disease progression. In this commentary, the author
      discusses four sources of bias that arise in such work. The focus is on Tyas et
      al.'s analyses (Am J Epidemiol 2007;165:1231-1238) of how the apolipoprotein E
      *E4 allele, a well-documented risk factor for Alzheimer's disease, influences
      progression of cognitive impairments from mild or global cognitive impairment to
      dementia or death. The author addresses four phenomena that can lead to spurious
      (noncausal) associations between apolipoprotein E *E4 status and rate of
      progression of cognitive impairments: beginning observations in the middle of a
      developing pathologic process, survivor bias, uncertainty in the timing of
      disease diagnosis, and nonlinear disease progression trajectories. Because these
      sources of bias are potentially relevant in any study of how risk factors for
      disease onset influence disease progression, the author advocates assessing their
      likely magnitude in specific contexts when interpreting results.

PMID- 17431010
TI  - Persistent binding of ligands to the aryl hydrocarbon receptor.
AB  - The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor
      that mediates many of the biological and toxic effects of halogenated aromatic
      hydrocarbons (HAHs), polycyclic aromatic hydrocarbons (PAHs), and other
      structurally diverse ligands. While HAHs are several orders of magnitude more
      potent in producing AhR-dependent biochemical effects than PAHs or other AhR
      agonists, only the HAHs have been observed to produce AhR-dependent toxicity in
      vivo. Here we have characterized the dissociation of a prototypical HAH ligand
      ([(3)H] 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]) and PAH-like ligand ([(3)H]
      beta-naphthoflavone [betaNF]) from the guinea pig, hamster, mouse, and rat
      hepatic cytosolic AhR in order to elucidate the relationship between the apparent
      ligand-binding affinities and the divergent potency of these chemicals. Both
      compounds dissociated very slowly from the AhR with the amount of specific
      binding remaining at 96 h ranging from 53% to 70% for [(3)H]TCDD and 26% to 85%
      for [(3)H] betaNF, depending upon the species examined. The rate of ligand
      dissociation was unaffected by protein concentration or incubation temperature.
      Preincubation of cytosol with 2,3,7,8-tetrachlorodibenzofuran, carbaryl, or
      primaquine, prior to the addition of [(3)H]TCDD, shifted the apparent IC(50) of
      these compounds as competitive AhR ligands by approximately 10- to 50-fold. Our
      results support the need for reassessment of previous AhR ligand-binding affinity
      calculations and competitive binding analysis since these measurements are not
      carried out at equilibrium binding conditions. Our studies suggest that AhR
      binding affinity/occupancy has little effect on the observed differences in the
      persistence of gene expression by HAHs and PAHs.

PMID- 17431012
TI  - Transitions to mild cognitive impairments, dementia, and death: findings from the
      Nun Study.
AB  - The potential of early interventions for dementia has increased interest in
      cognitive impairments less severe than dementia. However, predictors of the
      trajectory from intact cognition to dementia have not yet been clearly
      identified. The purpose of this study was to determine whether known risk factors
      for dementia increased the risk of mild cognitive impairments or progression from
      mild cognitive impairments to dementia. A polytomous logistic regression model
      was used, with parameters governing transitions within transient states (intact
      cognition, mild cognitive impairments, global impairment) estimated separately
      from parameters governing the transition from transient to absorbing state
      (dementia or death). Analyses were based on seven annual examinations (1991-2002)
      of 470 Nun Study participants aged > or = 75 years at baseline and living in the
      United States. Odds of developing dementia increased with age primarily for those
      with low educational levels. In these women, presence of an apolipoprotein E gene
      *E4 allele increased the odds more than fourfold by age 95 years. Age, education,
      and the apolipoprotein E gene were all significantly associated with mild
      cognitive impairments. Only age, however, was associated with progression to
      dementia. Thus, risk factors for dementia may operate primarily by predisposing
      individuals to develop mild cognitive impairments; subsequent progression to
      dementia then depends on only time and competing mortality.

PMID- 17431014
TI  - Expression of apoptosis-related markers in malignant epithelial tumours of the
      lacrimal gland and their relation to clinical outcome.
AB  - OBJECTIVE: To investigate the correlation between the expression of apoptosis
      related markers and prognosis in malignant epithelial tumours of the lacrimal
      gland. MATERIALS AND METHODS: Series of cases. PARTICIPANTS: Twenty one cases
      with malignant epithelial tumours of the lacrimal gland. Histological diagnosis
      was re-examined and blocks selected were evaluated for the following parameters:
      incidence of apoptosis with TUNEL assay, expression of p53 and Bcl-2 using
      monoclonal antibody. Predictors factors for survival, local recurrence and
      cumulative probability of death were statistically evaluated. RESULTS: Re
      eximination of the 21 specimens was as follow: 11 adenoid cystic carcinomas, 4
      mucoepidermoid carcinomas, 3 squamous cell carcinomas and 3 adenocarcinomas.
      Eleven of the 21 patients (53%) died during the follow-up period (4-192 months;
      mean 71). Bcl-2 staining >6% was significantly correlated with the death of
      patients. A statistically significant positive relationship for TUNEL and p53,
      and an inverse correlation for Bcl-2 staining, was demonstrated with overall
      survival. CONCLUSION: The correlation with survival of apoptotic index, p53 and
      Bcl-2 expression suggest the more tumour cells go in apoptosis, upregulating p53
      and down-regulating Bcl-2, the better the survival of patients. This study
      establishes a role of apoptosis-regulatory proteins in the pathogenesis of
      malignant epithelial lacrimal gland tumours, and supports the hypothesis that
      evaluation of the expression of apoptosis-related markers in these tumours may
      provide a prognostic tool.

PMID- 17431015
TI  - Ranibizumab (Lucentis) versus bevacizumab (Avastin): modelling cost
      effectiveness.
AB  - Two new drugs provide startling benefits in the treatment of age-related macular
      degeneration (AMD). The clinical and cost effectiveness of ranibizumab (Lucentis)
      was compared to that of bevacizumab (Avastin), which costs up to 100 times less.
      A cost effectiveness model was developed to assess the cost per quality adjusted
      life year (QALY) over 10 years. For predominantly classic AMD, the efficacy of
      bevacizumab relative to ranibizumab would have to be around 40% for the latter to
      achieve 30 k pounds per QALY, a NICE threshold. Similar but worse results applied
      to the other main forms of AMD, minimally occult and occult with no classic
      lesions. The price of ranibizumab would have to be drastically reduced for it to
      be cost effective. Continued unlicensed use of bevacizumab raises ethical, legal
      and policy questions. Public pressure may be the most potent weapon in persuading
      Genentech to license bevacizumab for AMD.

PMID- 17431016
TI  - The lazy shadow: a monocular counterpart to the Pulfrich stereo phenomenon.
AB  - BACKGROUND: The Pulfrich phenomenon is a dynamic stereo dysmetropsia attributed
      to an asymmetry of neural conduction between the eyes. The phenomenon may arise
      spontaneously with ocular and neurological disease and may be induced in normal
      subjects by placing a light-attenuating filter before one eye. By analogy, it is
      predicted that a localised variation of retinal illumination within one and the
      same eye should affect the perception of moving targets. METHODS: A rotating,
      nesting square display was generated by computer graphics. The inner square was
      painted bright white, the outer dim grey. Luminances, rates of rotation and
      angular sizes were varied. RESULTS: On rotation, the outer, dimmer square
      appeared to lag behind the inner, brighter one, as a "lazy shadow". The lag was
      measured quantitatively in normal observers by applying a compensatory lead to
      the lagging square. The magnitude of lag was found to depend on luminance, spin
      rate and visual angle. Lags exceeding 10 degrees were observed under optimum
      conditions. CONCLUSIONS: The experimental results confirm the existence of a
      monocular counterpart to the binocular Pulfrich phenomenon. Distortions of moving
      images are likely to occur spontaneously with monocular, localised visual field
      defects.

PMID- 17431017
TI  - Fundus autofluorescence of choroidal nevus and melanoma.
AB  - BACKGROUND: To describe autofluorescence patterns of choroidal melanocytic
      lesions using the Heidelberg Retinal Angiograph 2 system (HRA2). METHODS: 20
      patients with choroidal melanocytic lesions in the ocular fundus underwent
      ophthalmologic examination, fundus photography, autofluorescence and optical
      coherence tomography (OCT). Pathologic examination was performed on one
      enucleated eye with a large choroidal melanoma. RESULTS: 15 patients had
      choroidal nevi and 5 had malignant choroidal melanoma (1 small, 1 medium and 3
      large tumours). Choroidal nevi did not show any characteristic autofluorescence
      pattern, although secondary retinal pigment epithelium (RPE) changes, such as
      drusen and pigment epithelium detachment, appeared faintly hyperautofluorescent
      in 2 patients. Only the small malignant choroidal melanomas had prominent orange
      pigmentation, although all melanomas had an intense confluent
      hyperautofluorescent signal over the lesions. Pathology of one large malignant
      melanoma revealed lipofuscin underlying RPE. CONCLUSION: Most nevi did not have
      characteristic hyperautofluorescent features, but choroidal melanomas seemed to
      have a pattern of confluent hyperautofluorescence. Therefore, autofluorescence
      may be a useful non-invasive tool to assess lipofuscin in pigmented choroidal
      lesions, which may contribute to the diagnosis of malignancy. This hypothesis,
      however, remains to be confirmed in large prospective studies.

PMID- 17431018
TI  - Evaluation of repeatability for the automatic estimation of endothelial cell
      density in donor corneas.
AB  - BACKGROUND/AIMS: The repeatability of an automatic system for estimation of
      endothelial cell density (ECD) from microscopy images in donor corneas was
      assessed. METHODS: A computer program for the automatic ECD estimation from
      frequency analysis was previously presented. An evaluation of its repeatability
      was performed on a data set containing 200 corneas by assessing the accuracy and
      precision of automatic versus manual values. For each cornea, 2-21 images (1536
      total) at 100x for automatic ECD and one image at 200x for manual ECD were
      available. RESULTS: Accuracy of automatic ECDs was -45 (SD 99) cells/mm(2) (-2%
      (4%)). Precision of repeated automatic ECDs on the same cornea was 62 (30)
      cells/mm(2) (3% (1%)). The algorithm was also capable of identifying all non
      processable images. CONCLUSION: The proposed automatic technique proved to be
      reliable for its routine use in a typical eye bank setting like the one
      considered here.

PMID- 17431019
TI  - The key informant method: a novel means of ascertaining blind children in
      Bangladesh.
AB  - BACKGROUND: Most information on the causes of blindness has come from examining
      children in special education. To obtain a more representative population-based
      sample of children, a novel method was developed for ascertaining severe visually
      impaired (SVI) or blind (BL) children by training local volunteers to act as key
      informants (KIs). OBJECTIVE: To compare the demography and cause of blindness in
      children recruited by KIs with other ascertainment methods. METHOD: Children with
      SVI/BL were recruited in all 64 districts of Bangladesh. Three sources for case
      ascertainment were utilised: schools for the blind (SpEdu), community-based
      rehabilitation (CBR) programmes and KIs. All data were recorded using the
      standard WHO/PBL Eye Examination Record. RESULTS: 1935 children were recruited.
      Approximately 800 KIs were trained. The majority of the children were recruited
      by the KIs (64.3%). Children recruited by KIs were more likely to be female (odds
      ratio (OR) 1.6, p<0.001), of pre-school age (OR 14.1, p<0.001), from rural areas
      (OR 5.9, p<0.001), be multiply impaired (OR 3.1, p = 0.005) and be suffering from
      treatable eye diseases (OR 1.3, p = 0.005) when compared with those in SpEdu.
      Overall a child with an avoidable causes of SVI/BL had 40% (adjusted CI 1.1 to
      1.7, p = 0.015) and 30% (CI 1.0 to 1.7, p = 0.033) higher odds of being
      ascertained using the KIs compared with SpEdu and CBR methods, respectively.
      CONCLUSION: Using this innovative approach has resulted in one of the largest
      studies of SVI/BL children to date. The findings indicate that KIs can recruit
      large numbers of children quickly, and that the children they recruit are more
      likely to be representative of all blind children in the community.

PMID- 17431020
TI  - Complications in resident-performed phacoemulsification cataract surgery at New
      Jersey Medical School.
AB  - AIM: To describe the complications related to cataract surgery performed by
      phacoemulsification technique by third-year ophthalmology residents at New Jersey
      Medical School, who are trained to perform phacoemulsification without any prior
      experience with extracapsular extraction. DESIGN: Retrospective, observational
      case series. METHODS: A retrospective chart review of 755 patients who underwent
      cataract surgery by third-year residents between July 2000 and June 2005 at the
      Institute of Ophthalmology and Visual Science was performed. Details of
      intraoperative complications (posterior capsular rupture, vitreous loss,
      subluxation of lens fragments into the vitreous, extracapsular cases converted to
      phacoemulsification, retinal detachment, vitreous haemorrhage and haemorrhagic
      choroidals) of the cases done by phacoemulsification technique were recorded.
      Results were analysed and compared with complication rates reported from other
      residency programmes and from experienced ophthalmologists. RESULTS: Of 755
      cataract surgeries, 719 were performed using phacoemulsification technique.
      Posterior capsule disruption occurred in 48 (6.7%), vitreous loss in 39 (5.4%)
      and dislocated lenticular fragments in 7 (1.0%) of 719 cases that underwent
      phacoemulsification technique. Subsequent pars plana lensectomy was required in 5
      (0.7%) cases; 1 case (0.1%) experienced retinal detachment and haemorrhagic
      choroidal detachment. CONCLUSION: The residents can perform phacoemulsification
      well with a very low complication rate, without prior training with extracapsular
      cataract extraction technique.

PMID- 17431021
TI  - Nuclear magnetic resonance analysis of emulsified silicone oil RMN-3 (Oxane HD).
AB  - BACKGROUND: Oxane HD is a mixture of 5700 cs silicone oil and RMN-3 (a partly
      fluorinated olefin), which has a specific gravity greater than water, thereby
      enabling endotamponade of inferior retinal breaks. Droplets of emulsified oil
      were found in the anterior chamber of two patients with complex retinal
      detachments who had been treated with Oxane HD. Samples removed from these two
      eyes were analysed in order to investigate the nature of the emulsified
      substance. METHODS: Samples were dissolved in CDCl3 and, if necessary, dried
      using magnesium sulphate. Nuclear magnetic resonance (NMR) was used to compare
      these samples with the unused commercial product. RESULTS: NMR analysis of the
      samples removed from the anterior segment of both eyes were mainly silicone oil
      with only trace amounts of RMN-3. Samples taken from different areas of an unused
      syringe of Oxane HD demonstrated varying concentrations of the RMN-3 compound
      within the silicone oil. CONCLUSION: First, the mixture of RMN-3 and silicone oil
      is not homogenous either in vitro or in vivo. Second, emulsified oil found in the
      anterior chamber is composed almost entirely of silicone oil, containing only
      trace amounts of RMN-3.

PMID- 17431022
TI  - Computer models of auxin transport: a review and commentary.
AB  - With the recent proliferation of computer models of auxin transport, it is
      important that plant biologists understand something about these techniques and
      how to evaluate them. The paper begins with a brief introduction to the parts of
      a computer model, followed by a discussion of the limitations of the most common
      auxin modelling technique. Lastly, several recent models of organ initiation in
      the shoot apical meristem (i.e. phyllotaxis) are reviewed. The cell and molecular
      biology of phyllotaxis is now understood well enough that computer models can go
      beyond a simple 'proof of principle' and start to provide insights into gene
      function.

PMID- 17431023
TI  - Reduction of ethylene emission from Scots pine elicited by insect egg secretion.
AB  - Pinus sylvestris L. is known to activate indirect defence in response to attack
      by an herbivorous sawfly. Egg deposition by the sawfly Diprion pini L. induces
      pine to release, three days after egg laying, locally and systemically terpenoid
      volatiles that attract parasitoids to kill the eggs. The elicitor of the pine's
      response is located in the sawfly's oviduct secretion enveloping the eggs after
      deposition. Application of this secretion on twigs with artificially conducted
      ovipositional woundings mimics the effects of egg deposition. Furthermore,
      jasmonic acid (JA) induces a volatile pattern similar, but not identical, to the
      one induced by egg deposition. To gain deeper insight into the transduction of
      plant signals induced by herbivore egg deposition, it was investigated whether
      ethylene emission from pine is affected by sawfly egg deposition. Systemically
      induced ethylene emission from differently treated pine twigs was monitored for a
      period of 3 d after treatment. Ethylene emissions from untreated control twigs
      were compared with those from twigs treated as follows: (i) sawfly egg secretion
      [=oviduct secretion (OVI)] was transferred on artificially wounded pine needles
      (attractive volatiles), (ii) needles were artificially wounded (non-attractive
      volatiles), and (iii) the twig was supplied with JA (attractive volatiles).
      Ethylene emission from systemically OVI-induced twigs was significantly lower
      than from untreated controls, whereas artificial wounding had no detectable
      effect. JA-treated twigs released much more ethylene and showed higher
      variability of ethylene emission than artificially wounded twigs and OVI-treated
      ones. Ethylene emissions from pine after the various treatments studied here are
      discussed with respect to known effects of insect feeding on ethylene release
      from plants.

PMID- 17431024
TI  - Arabidopsis peroxin 16 trafficks through the ER and an intermediate compartment
      to pre-existing peroxisomes via overlapping molecular targeting signals.
AB  - Previously it has been shown that the endogenous Arabidopsis peroxin, AtPEX16,
      coexisted at steady state in membranes of the endoplasmic reticulum (ER) and
      peroxisomes. Herein, an ER-to-peroxisome trafficking pathway and the requisite
      molecular targeting signals for mycAtPEX16 transiently expressed in Arabidopsis
      and tobacco BY-2 suspension cells are described. Immunofluorescent mycAtPEX16 was
      observed initially in the cytosol (<2 h) and subsequently (2-4 h) in
      perinuclear/reticular ER and non-Golgi/non-peroxisome structures termed the ER
      peroxisome intermediate compartment. After 4 h, all catalase- and ascorbate
      peroxidase-containing peroxisomes also possessed mycAtPEX16, indicative of
      mycAtPEX16 sorting to pre-existing peroxisomes. Incubations of bombarded cells at
      15 degrees C, or in brefeldin A at 25 degrees C, resulted in accumulations of
      mycAtPEX16 within the ER. Following re-equilibration of cold-treated cells at 25
      degrees C, or removal of brefeldin A, mycAtPEX16 was observed mainly in the ER
      peroxisome intermediate compartment, and later within all of the peroxisomes in
      both species. Two internal membrane helices and the intervening sequence
      including the amino acid residues -VRS- were found necessary and sufficient for
      targeting AtPEX16 first to the ER and then to peroxisomes. Individual targeting
      signals for these organelles were indistinguishable, indicative of overlapping
      signal(s). In summary, the trafficking study of AtPEX16 revealed a dynamic link
      between the ER and pre-existing peroxisomes, which provided novel data in support
      of an upgraded semi-autonomous peroxisome model portraying participation of the
      ER in the sorting of certain peroxisome membrane proteins, such as AtPEX16,
      through an intermediate compartment to pre-existing plant peroxisomes.

PMID- 17431025
TI  - High temperature stress and spikelet fertility in rice (Oryza sativa L.).
AB  - In future climates, greater heat tolerance at anthesis will be required in rice.
      The effect of high temperature at anthesis on spikelet fertility was studied on
      IR64 (lowland indica) and Azucena (upland japonica) at 29.6 degrees C (control),
      33.7 degrees C, and 36.2 degrees C tissue temperatures. The objectives of the
      study were to: (i) determine the effect of temperature on flowering pattern; (ii)
      examine the effect of time of day of spikelet anthesis relative to a high
      temperature episode on spikelet fertility; and (iii) study the interactions
      between duration of exposure and temperature on spikelet fertility. Plants were
      grown at 30/24 degrees C day/night temperature in a greenhouse and transferred to
      growth cabinets for the temperature treatments. Individual spikelets were marked
      with paint to relate fertility to the time of exposure to different temperatures
      and durations. In both genotypes the pattern of flowering was similar, and peak
      anthesis occurred between 10.30 h and 11.30 h at 29.2 degrees C, and about 45 min
      earlier at 36.2 degrees C. In IR64, high temperature increased the number of
      spikelets reaching anthesis, whereas in Azucena numbers were reduced. In both
      genotypes<or=1 h exposure to>or=33.7 degrees C at anthesis caused sterility. In
      IR64, there was no interaction between temperature and duration of exposure, and
      spikelet fertility was reduced by about 7% per degrees C>29.6 degrees C. In
      Azucena there was a significant interaction and spikelet fertility was reduced by
      2.4% degrees Cd-1 above a threshold of 33 degrees C. Marking individual spikelets
      is an effective method to phenotype genotypes and lines for heat tolerance that
      removes any apparent tolerance due to temporal escape.

PMID- 17431026
TI  - Calystegines in potatoes with genetically engineered carbohydrate metabolism.
AB  - Calystegines are hydroxylated nortropane alkaloids derived from the tropane
      alkaloid biosynthetic pathway. They are strong glycosidase inhibitors and occur
      in vegetables such as potatoes, tomatoes, and cabbage. Calystegine accumulation
      in root cultures was described to increase with carbohydrate availability.
      Whether this is indicative for the in planta situation is as yet unknown.
      Potatoes are model plants for the study of carbohydrate metabolism. Numerous
      transgenic potato lines with altered carbohydrate metabolism are available, but
      rarely were examined for alterations in secondary metabolism. In this study,
      calystegine accumulation and expression of biosynthetic enzymes were related to
      genetic modifications in carbohydrate metabolism in potato tubers. Tubers
      contained more soluble sugars due to overexpression of yeast invertase in the
      apoplast or in the cytosol, or due to antisense suppression of sucrose synthase.
      It is shown that the major part of calystegines in tubers originated from
      biosynthesis in plant roots. Yet, tuber calystegine levels responded to genetic
      alterations of carbohydrate metabolism in tubers. The strongest increase in
      calystegines was found in tubers with suppressed sucrose synthase activity.
      Transcripts and enzyme activities involved in calystegine biosynthesis largely
      concurred with product accumulation. Whole plant organs were examined similarly
      and displayed higher calystegines and corresponding enzyme activities in roots
      and stolons of plants with enhanced soluble sugars. Increases in calystegines
      appear to be linked to sucrose availability.

PMID- 17431027
TI  - A proteomic and targeted metabolomic approach to investigate change in Lolium
      perenne roots when challenged with glycine.
AB  - A combined proteomic and isotope tracer approach was used to investigate the
      impact of supplying N as glycine to roots of Lolium perenne. Initially, ammonium
      nitrate was supplied to all plants, after which half received glycine as their
      sole N source, while the remainder continued to receive ammonium nitrate. Plants
      supplied with glycine acquired less N than those receiving the mineral source,
      resulting in reduced root nitrate concentrations. The amino acid complement of
      roots was also strongly affected by the form of N supplied, and 15N labelling
      indicated that the biochemical fate of acquired N in roots was dependent on the
      form of N available for uptake. Proteomic analysis of Lolium roots indicated that
      6% of 627 root proteins resolved on 2D gels changed in abundance in response to
      the form of N applied. Multivariate analysis of protein abundance clearly
      discriminated the proteomes of L. perenne roots as a function of treatment
      applied. Seven affected proteins were identified (mostly by protein homology with
      sequenced species), including methionine adenosyltransferase, an enzyme involved
      in glycine metabolism. Although some changes in root amino acid and protein
      complements were due to responses to reduced N supply, both the distinct fate of
      15N tracers and the abundances of identified proteins could be attributed
      specifically to the form of N available to roots. The results demonstrate the
      potential of targeted proteomic approaches to identify functioning of plants
      where more traditional methods cannot resolve multiple, co-incident biological
      interactions and element fluxes.

PMID- 17431028
TI  - Sucrose supply to nematode-induced syncytia depends on the apoplasmic and
      symplasmic pathways.
AB  - The plant parasitic nematode Heterodera schachtii induces syncytial feeding
      structures in the roots of host plants. Nematode-induced syncytia become strong
      sink tissues in the plant solute circulation system as the parasites start
      withdrawing nutrients. In the present work, the expression pattern of the phloem
      specific sucrose transporter AtSUC4 (also described as AtSUT4) is analysed in
      syncytia induced by H. schachtii and it is compared with that of AtSUC2, another
      phloem-specific sucrose transporter, which is expressed in syncytia. The temporal
      expression pattern was monitored by GUS-tests and real-time RT-PCR, while the
      localization within the syncytia was performed using in situ RT-PCR. In this
      context, the concentration of sucrose in infection sites was also analysed and,
      in fact, an increase in response to syncytium development was found. Silencing of
      the AtSUC4 gene finally resulted in a significant reduction of female nematode
      development, thus demonstrating a function for this gene for the first time. It
      is therefore concluded that AtSUC4 plays a significant role in the early phase of
      syncytium differentiation when functional plasmodesmata to the phloem are not yet
      established. It is further concluded that, during syncytium establishment,
      transporters are responsible for sucrose supply and, at a later stage, when a
      connection to the phloem is established via plasmodesmata, transporters are
      required for sucrose retrieval.

PMID- 17431029
TI  - Metabolism, pharmacokinetics, and excretion of a nonpeptidic substance P receptor
      antagonist, ezlopitant, in normal healthy male volunteers: characterization of
      polar metabolites by chemical derivatization with dansyl chloride.
AB  - The excretion, biotransformation, and pharmacokinetics of ezlopitant [(2
      benzhydryl-1-aza-bicyclo[2.2.2]oct-3-yl)-(5-isopropyl-2-methoxy-benzyl)-amine], a
      substance P receptor antagonist, were investigated in healthy male volunteers
      after oral administration of a single 200-mg (approximately 93 microCi/subject)
      dose of [(14)C]ezlopitant. The total recovery of administered radioactive dose
      was 82.8 +/- 5.1, with 32.0 +/- 4.2% in the urine and 50.8 +/- 1.4% in the feces.
      Mean observed maximal serum concentrations for ezlopitant and total radioactivity
      were achieved at approximately 2 h after oral administration; thus, ezlopitant
      was rapidly absorbed. Ezlopitant was extensively metabolized in humans, since no
      unchanged drug was detected in urine and feces. The major pathway of ezlopitant
      in humans was the result of the oxidation of the isopropyl side chain to form the
      omega-hydroxy and omega-1-hydroxy (M16) metabolites. M16 and omega,omega-1
      dihydroxy (1,2-dihydroxy, M12) were identified as the major circulating
      metabolites accounting for 64.6 and 15.4% of total circulating radioactivity,
      respectively. In feces, the major metabolite M14 was characterized as the
      propionic acid metabolite and formed by further oxidation of the omega-hydroxy
      metabolite. The urinary metabolites were the result of cleaved metabolites caused
      by oxidative dealkylation of the 2-benzhydryl-1-aza-bicyclo[2.2.2]oct-3-yl
      moiety. The metabolites (M1A, M1B, and M4), approximately 34% of the total
      radioactivity in urine, were identified as benzyl amine derivatives. These were
      polar metabolites that were further characterized using the reaction with dansyl
      chloride to derivatize the primary amines and phenol moieties to less polar
      analytes. The other metabolites were the result of O-demethylation,
      dehydrogenation of the isopropyl group, and oxidation on the quinuclidine moiety.

PMID- 17431030
TI  - Absorption, metabolism, and excretion of [(14)C]MK-0524, a prostaglandin D(2)
      receptor antagonist, in humans.
AB  - [(3R)-4-(4-Chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4
      tetrahydrocyclopentaindol-3-yl]acetic acid (MK-0524) is a potent orally active
      human prostaglandin D(2) receptor 1 antagonist that is currently under
      development for the prevention of niacin-induced flushing. The metabolism and
      excretion of [(14)C]MK-0524 in humans were investigated in six healthy human
      volunteers following a single p.o. dose of 40 mg (202 microCi). [(14)C]MK-0524
      was absorbed rapidly, with plasma C(max) achieved 1 to 1.5 h postdose. The major
      route of excretion of radioactivity was via the feces, with 68% of the
      administered dose recovered in feces. Urinary excretion averaged 22% of the
      administered dose, for a total excretion recovery of approximately 90%. The
      majority of the dose was excreted within 96 h following dosing. Parent compound
      was the primary radioactive component circulating in plasma, comprising 42 to 72%
      of the total radioactivity in plasma for up to 12 h. The only other radioactive
      component detected in plasma was M2, the acyl glucuronic acid conjugate of the
      parent compound. The major radioactive component in urine was M2, representing
      64% of the total radioactivity. Minor metabolites included hydroxylated epimers
      (M1/M4) and their glucuronic acid conjugates, which occurred in the urine as urea
      adducts, formed presumably during storage of samples. Fecal radioactivity
      profiles mainly comprised the parent compound, originating from unabsorbed parent
      and/or hydrolyzed glucuronic acid conjugate of the parent compound. Therefore, in
      humans, MK-0524 was eliminated primarily via metabolism to the acyl glucuronic
      acid conjugate, followed by excretion of the conjugate into bile and eventually
      into feces.

PMID- 17431031
TI  - Cytochrome P450 eicosanoids are activators of peroxisome proliferator-activated
      receptor alpha.
AB  - Cytochrome P450 (P450) eicosanoids regulate vascular tone, renal tubular
      transport, cellular proliferation, and inflammation. Both the CYP4A omega
      hydroxylases, which catalyze 20-hydroxyeicosatetraenoic acid (20-HETE) formation,
      and soluble epoxide hydrolase (sEH), which catalyzes epoxyeicosatrienoic acid
      (EET) degradation to the dihydroxyeicosatrienoic acids (DHETs), are induced upon
      activation of peroxisome proliferator-activated receptor alpha (PPARalpha) by
      fatty acids and fibrates. In contrast, the CYP2C epoxygenases, which are
      responsible for EET formation, are repressed after fibrate treatment. We show
      here that P450 eicosanoids can bind to and activate PPARalpha and result in the
      modulation of PPARalpha target gene expression. In transactivation assays, 14,15
      DHET, 11,2-EET, and 20-HETE were potent activators of PPARalpha. Gel shift assays
      showed that EETs, DHETs, and 20-HETE induced PPARalpha-specific binding to its
      cognate response element. Expression of apolipoprotein A-I was decreased 70% by
      20-HETE, whereas apolipoprotein A-II expression was increased up to 3-fold by
      11,12-EET, 14,15-DHET, and 20-HETE. In addition, P450 eicosanoids induced CYP4A1,
      sEH, and CYP2C11 expression, suggesting that they can regulate their own levels.
      Given that P450 eicosanoids have multiple cardiovascular effects, pharmacological
      modulation of their formation and/or degradation may yield therapeutic benefits.

PMID- 17431032
TI  - Application of the dispersion model to describe disposition kinetics of markers
      in the dual perfused rat liver.
AB  - The liver receives two blood supplies, portal and hepatic, yet most in situ
      studies use only portal perfusion. A model based on dispersion principles was
      developed to provide baseline data of the dual perfused rat liver preparation by
      characterizing the temporal outflow profiles of noneliminated reference markers
      (vascular marker, red blood cells; extracellular markers, albumin, sucrose; and
      intracellular markers, urea, water). The model consists of two components: the
      common and a specific arterial space operating in parallel. The common space
      receives all the portal flow and some of the arterial flow; the remaining
      arterial flow perfuses the specific space. Each space is divided into three
      subspaces: vascular, interstitial, and intracellular. The extent of axial
      spreading of solute on passage through the common and specific spaces is
      characterized by their respective dispersion numbers, D(N). The model was fully
      characterized by analysis of the outflow data following independent bolus
      administration into the portal vein and hepatic artery. The model provided a good
      fit of the data for all reference compounds. The estimate of the fraction of the
      total space assigned to the specific arterial space varied from 4 to 11%, with a
      mean value of 9%. The estimated D(N) was always small (<0.25) and tended to be
      greater for the common space (0.08-0.23) than the specific space (0.05-0.12).
      However, for each space, there was no significant difference in the D(N) value
      among all reference markers; this is assumed to arise because all markers are
      reflecting a common feature, the heterogeneity of the microvasculature.

PMID- 17431033
TI  - Timolol metabolism in human liver microsomes is mediated principally by CYP2D6.
AB  - Timolol has mainly been used topically for the treatment of glaucoma. It has been
      suggested that the drug is metabolized by cytochrome P450 CYP2D6. The matter has
      not, however, been extensively studied. The aim here was to tentatively identify
      timolol metabolites and to determine the P450-associated metabolic and
      interaction properties of timolol in vitro. Four metabolites were identified, the
      most abundant being a hydroxy metabolite, M1. The K(m) value for the formation of
      M1 was 23.8 microM in human liver microsomes. Metabolism of timolol with
      recombinant P450s and correlation analysis have confirmed the conception that the
      drug is metabolized principally by CYP2D6, CYP2C19 being only a minor contributor
      (<10%) to the intrinsic microsomal clearance. The CYP2D6 inhibitor quinidine
      proved a potent competitive inhibitor of timolol metabolism, with an in vitro
      K(i) value of 0.08 microM. Fluvoxamine, an inhibitor of CYP2C19, inhibited
      timolol metabolism to a lesser extent, confirming its minor contribution. Timolol
      itself did not inhibit CYP2D6-catalyzed dextromethorphan O-demethylation. Judging
      from the disappearance of timolol in human liver homogenate, the in vivo half
      life was extrapolated to be about 3 h, an estimate close to the half-life of
      about 2 to 5 h observed in vivo. In conclusion, the inhibition of timolol
      metabolism by quinidine should be taken into account when patients are treated
      with timolol. However, when plasma timolol concentrations in patients remain low
      (< or = 0.2 microg/l), it is suggested that such interaction is of minor clinical
      relevance.

PMID- 17431034
TI  - CYP1A induction and human risk assessment: an evolving tale of in vitro and in
      vivo studies.
AB  - CYP1A1 and 1A2 play critical roles in the metabolic activation of carcinogenic
      polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines/amides
      (HAAs), respectively, to electrophilic reactive intermediates, leading to
      toxicity and cancer. CYP1As are highly inducible by PAHs and halogenated aromatic
      hydrocarbons via aryl hydrocarbon receptor-mediated gene transcription. The
      impact of CYP1A induction on the carcinogenic and toxic potentials of
      environmental, occupational, dietary, and therapeutic chemicals has been a
      central focus of human risk evaluation and has broadly influenced the fields of
      cancer research, toxicology, pharmacology, and risk assessment over the past half
      century. From the early discovery of CYP1A induction and its role in protection
      against chemical carcinogenesis in intact animals, to the establishment of CYP1A
      enzymes as the principal cytochromes P450 for bioactivation of PAHs and HAAs in
      in vitro assays, to the recent realization of an essential protective role of
      CYP1A in benzo[a]pyrene-induced lethality and carcinogenesis with CYP1A knockout
      mice, the understanding of the interrelation between CYP1A induction and chemical
      safety has followed a full circle. This unique path of CYP1A research underscores
      the importance of whole animal and human studies in chemical safety evaluation.

PMID- 17431035
TI  - Identification of the special pair of photosystem II in a chlorophyll d-dominated
      cyanobacterium.
AB  - The composition of photosystem II (PSII) in the chlorophyll (Chl) d-dominated
      cyanobacterium Acaryochloris marina MBIC 11017 was investigated to enhance the
      general understanding of the energetics of the PSII reaction center. We first
      purified photochemically active complexes consisting of a 47-kDa Chl protein
      (CP47), CP43' (PcbC), D1, D2, cytochrome b(559), PsbI, and a small polypeptide.
      The pigment composition per two pheophytin (Phe) a molecules was 55 +/- 7 Chl d,
      3.0 +/- 0.4 Chl a, 17 +/- 3 alpha-carotene, and 1.4 +/- 0.2 plastoquinone-9. The
      special pair was detected by a reversible absorption change at 713 nm (P713)
      together with a cation radical band at 842 nm. FTIR difference spectra of the
      specific bands of a 3-formyl group allowed assignment of the special pair. The
      combined results indicate that the special pair comprises a Chl d homodimer. The
      primary electron acceptor was shown by photoaccumulation to be Phe a, and its
      potential was shifted to a higher value than that in the Chl a/Phe a system. The
      overall energetics of PSII in the Chl d system are adjusted to changes in the
      redox potentials, with P713 as the special pair using a lower light energy at 713
      nm. Taking into account the reported downward shift in the potential of the
      special pair of photosystem I (P740) in A. marina, our findings lend support to
      the idea that changes in photosynthetic pigments combine with a modification of
      the redox potentials of electron transfer components to give rise to an energetic
      adjustment of the total reaction system.

PMID- 17431036
TI  - The role of singlet oxygen and oxygen concentration in photodynamic inactivation
      of bacteria.
AB  - New antibacterial strategies are required in view of the increasing resistance of
      bacteria to antibiotics. One promising technique involves the photodynamic
      inactivation of bacteria. Upon exposure to light, a photosensitizer in bacteria
      can generate singlet oxygen, which oxidizes proteins or lipids, leading to
      bacteria death. To elucidate the oxidative processes that occur during killing of
      bacteria, Staphylococcus aureus was incubated with a standard photosensitizer,
      and the generation and decay of singlet oxygen was detected directly by its
      luminescence at 1,270 nm. At low bacterial concentrations, the time-resolved
      luminescence of singlet oxygen showed a decay time of 6 +/- 2 micros, which is an
      intermediate time for singlet oxygen decay in phospholipids of membranes (14 +/-
      2 micros) and in the surrounding water (3.5 +/- 0.5 micros). Obviously, at low
      bacterial concentrations, singlet oxygen had sufficient access to water outside
      of S. aureus by diffusion. Thus, singlet oxygen seems to be generated in the
      outer cell wall areas or in adjacent cytoplasmic membranes of S. aureus. In
      addition, the detection of singlet oxygen luminescence can be used as a sensor of
      intracellular oxygen concentration. When singlet oxygen luminescence was measured
      at higher bacterial concentrations, the decay time increased significantly, up to
      approximately 40 micros, because of oxygen depletion at these concentrations.
      This observation is an important indicator that oxygen supply is a crucial factor
      in the efficacy of photodynamic inactivation of bacteria, and will be of
      particular significance should this approach be used against multiresistant
      bacteria.

PMID- 17431037
TI  - Human prostate epithelium lacks Wee1A-mediated DNA damage-induced checkpoint
      enforcement.
AB  - Cellular DNA damage triggers the DNA damage response pathway and leads to
      enforcement of cell cycle checkpoints, which are essential for the maintenance of
      genomic integrity and are activated in early stages of tumorigenesis. A special
      feature of prostate cancer is its high incidence and multifocality. To address
      the functionality of DNA damage checkpoints in the prostate, we analyzed the
      responses of human primary prostate epithelial cells (HPECs) and freshly isolated
      human prostate tissues to gamma-irradiation. We find that gamma-irradiation
      activates the ataxia telangiectasia mutated-associated DNA damage response
      pathway in the HPECs but that the clearance of phosphorylated histone H2AX
      (gammaH2AX) foci is delayed. Surprisingly, gamma-irradiated HPECs were unable to
      enforce cell cycle checkpoint arrest and had sustained cyclin-dependent kinase 2
      (Cdk2)-associated kinase activity because of a lack of inhibitory Cdk
      phosphorylation by Wee1A tyrosine kinase. We further show that HPECs express low
      levels of Wee1A and that ectopic Wee1A efficiently rescues the checkpoints. We
      recapitulate the absence of checkpoint responses in epithelium of ex vivo
      irradiated human prostate tissue despite robust induction of gammaH2AX. The
      findings show that prostate epithelium has a surprising inability to control
      checkpoint arrest, the lack of which may predispose to accrual of DNA lesions.

PMID- 17431039
TI  - Evaluation of the impact of errors in the measurement of backfat depth on the
      prediction of fat-free lean mass.
AB  - The development of regression equations to predict carcass composition typically
      assumes that the independent variables, such as backfat depth, are measured
      without error. However, technological and operator-specific types of measurement
      errors do exist. To evaluate the impact of measurement error for backfat depth,
      Monte Carlo simulation was used to model carcass fat-free lean mass (FFLM) in
      pigs. In the simulation, FFLM was a linear function of carcass weight and actual
      backfat depth (ABFD). Carcass weight was assumed to be measured without error,
      but measurement errors were generated such that the correlation (r(BF)) of the
      measured backfat depth (BFD) and ABFD ranged from 0.70 to 0.95. Two types of
      measurement errors were simulated: 1) constant variation that was additive to the
      variance of ABFD, and 2) variation proportional to the ABFD that was additive to
      the variance in ABFD. A total of 1,000 replications of 1,000 pigs were simulated.
      Within each type of measurement error, the absolute values of the regression
      coefficients and R2 values of the equations decreased as r(BF) decreased. The
      probability of the backfat depth squared (BFD2) being significant (P < 0.05) in
      the regression equation was increased when the measurement errors were
      proportional to ABFD. The occurrence of a significant BFD2 variable was 792 times
      out of 1,000 replications when r(BF) = 0.95 and increased to 996 times out of
      1,000 when r(BF) = 0.85 for BFD with type 2 measurement errors. The inclusion of
      a CW x BFD variable in the regression equations (P < 0.05) increased (270 to 423
      times out of 1,000) as r(BF) decreased from 0.85 to 0.70 for BFD with type 2
      errors. Equations developed from BFD with measurement errors resulted in biased
      predictions of FFLM and changes in FFLM per unit change in BFD. The level and
      type of measurement errors that exist in the independent variables should be
      evaluated.

PMID- 17431040
TI  - Urea metabolism in beef steers grazing Bermudagrass, Caucasian bluestem, or
      gamagrass pastures varying in plant morphology, protein content, and protein
      composition.
AB  - Pastures of Bermudagrass (Cynodon dactylon, BG), Caucasian bluestem (Bothriochloa
      caucasica, CBS), and gamagrass (Tripsacum dactyloides, GG) were evaluated from
      the perspectives of forage composition, selection during grazing, and N
      metabolism in beef steers. All pastures were fertilized with 78 kg/ha of N
      approximately 60 and 30 d before sample collection. In 2000 and 2001, 12 steers
      (250 kg of BW) were blocked based on BW and then assigned randomly to a
      replicated, randomized complete block design, with 2 pastures of each forage and
      2 steers per pasture. Three other steers with esophageal fistulas were used to
      collect masticate samples to represent intake preferences. Herbage mass was
      >1,900 kg/ha. After at least 14 d of adaptation, urine and blood samples were
      collected for determination of serum urea N and percentage of urinary N in the
      form of urea. One steer per pasture (6 steers per year) was infused i.v. with
      (15,15)N urea for 50 h before collecting urine for 6 h to measure urea N
      enrichment, urea entry rate, urinary urea excretion, gut urea recycling, and
      return of urea N to the ornithine cycle. The canopy leaf:stem DM ratio differed
      (P = 0.01) among BG (0.50), CBS (1.01), and GG (4.00). Caucasian bluestem had
      less CP (% of DM) than GG or BG in the canopy (9.6 vs. 12.0 or 12.3, P = 0.07)
      and in the masticate (9.8 vs. 14.7 or 13.9, P = 0.04). Bermudagrass had less true
      protein (% of CP) than CBS or GG in the canopy (72.9 vs. 83.3 or 83.0, P = 0.07)
      and in the masticate (73.7 vs. 85.8 or 88.0, P = 0.04). Compared with GG and BG,
      CBS had less serum urea N (10.1 or 12.2 vs. 2.5 mM, P = 0.01), urea entry rate
      (353 or 391 vs. 209 mmol of N/h, P = 0.07), and urinary urea excretion (105 or 95
      vs. 18 mmol of N/h, P = 0.04), and a greater return of urea N to the ornithine
      cycle as a proportion of gut urea recycling (0.109 or 0.118 vs. 0.231, P = 0.02).
      Urea production and recycling in these steers responded more to the N
      concentration in the grasses than to differences in plant protein fractions.
      There was no evidence of improved N capture by the steers due to changes in the
      leaf:stem ratio among the grasses at the herbage mass evaluated.

PMID- 17431041
TI  - Effect of previous locoweed (Astragalus and Oxytropis species) intoxication on
      conditioned taste aversions in horses and sheep.
AB  - Locoweed species (Astragalus and Oxytropis spp.) are a serious toxic plant
      problem for grazing livestock. Horses and sheep have been conditioned to avoid
      eating locoweed using the aversive agent LiCl. The objective of this study was to
      determine if previous locoweed intoxication affects food aversion learning in
      horses and sheep. Horses and sheep were divided into 3 treatment groups: control
      (not fed locoweed and not averted to a novel feed); locoweed-novel feed averted
      (fed locoweed and averted to a novel feed); and averted (not fed locoweed and
      averted to a novel feed). Animals in the locoweed-novel feed averted groups were
      fed locoweed during 2 periods of 21 and 14 d, respectively, with each feeding
      period followed by a 14-d recovery period. Animals were averted to a novel test
      feed at the end of the first locoweed-feeding period, and periodically evaluated
      for the strength and persistence of the aversion. During the first recovery
      period, locoweed-novel feed averted horses ate less (9.5% of amount offered) of
      the test feed than did control horses (99.8%) and did not generally differ from
      averted horses (0%). During recovery period 2, locoweed-novel feed averted horses
      (4.3%) differed (P = 0.001) in consumption (% of offered) of the test feed from
      controls (100%) and the averted group (0%). Locoweed-novel feed averted sheep
      differed (P = 0.001) from controls (14.4 vs. 99.5%, respectively, during recovery
      period 1), whereas locoweed-novel feed averted sheep did not differ (P > 0.50)
      from averted sheep (0.6%). During the second recovery period, control sheep
      (100%) differed (P < 0.05) from averted (0%) and locoweed-novel feed averted
      (12.2%) groups. Two intoxicated sheep (locoweed-novel feed averted) partially
      extinguished the aversion during the first recovery period, but an additional
      dose of LiCl restored the aversion. Two of 3 intoxicated horses had strong
      aversions that persisted without extinction; 1 horse in the locoweed-novel feed
      averted group had a weaker aversion. These findings suggest that horses and sheep
      previously intoxicated by locoweeds can form strong and persistent aversions to a
      novel feed, but in some animals, those aversions may not be as strong as in
      animals that were never intoxicated.

PMID- 17431038
TI  - Plastidial fatty acid levels regulate resistance gene-dependent defense signaling
      in Arabidopsis.
AB  - In Arabidopsis, resistance to Turnip Crinkle Virus (TCV) depends on the
      resistance (R) gene, HRT, and the recessive locus rrt. Resistance also depends on
      salicylic acid (SA), EDS1, and PAD4. Exogenous application of SA confers
      resistance in RRT-containing plants by increasing HRT transcript levels in a PAD4
      dependent manner. Here we report that reduction of oleic acid (18:1) can also
      induce HRT gene expression and confer resistance to TCV. However, the 18:1
      regulated pathway is independent of SA, rrt, EDS1, and PAD4. Reducing the levels
      of 18:1, via a mutation in the SSI2-encoded stearoyl-acyl carrier protein
      desaturase, or by exogenous application of glycerol, increased transcript levels
      of HRT as well as several other R genes. Second-site mutations in the ACT1
      encoded glycerol-3-phosphate acyltransferase or GLY1-encoded glycerol-3-phosphate
      dehydrogenase restored 18:1 levels in HRT ssi2 plants and reestablished a
      dependence on rrt. Resistance to TCV and HRT gene expression in HRT act1 plants
      was inducible by SA but not by glycerol, whereas that in HRT pad4 plants was
      inducible by glycerol but not by SA. The low 18:1-mediated induction of R gene
      expression was also dependent on ACT1 but independent of EDS1, PAD4, and RAR1.
      Intriguingly, TCV inoculation did not activate this 18:1-regulated pathway in HRT
      plants, but instead resulted in the induction of several genes that encode 18:1
      synthesizing isozymes. These results suggest that the 18:1-regulated pathway may
      be specifically targeted during pathogen infection and that altering 18:1 levels
      may serve as a unique strategy for promoting disease resistance.

PMID- 17431042
TI  - Diet mixing time affects nursery pig performance.
AB  - The objective of this study was to determine the effects of mixing time (mixer
      efficiency) of diets containing several low-inclusion ingredients (crystalline
      AA, ZnO, a medication, and vitamin and trace mineral premixes) on growth
      performance of nursery pigs. In a pilot study, mixing efficiency of a 1,360-kg
      capacity, horizontal ribbon mixer was evaluated with salt of different particle
      sizes (440, 730, 2,000, and 3,000 microm). Sample preparation was evaluated by
      analyzing diet samples as collected (unground) or by grinding the entire sample
      to approximately 400 microm in particle size (ground). Diets (907 kg) were mixed,
      and samples were collected after 0, 30, 60, 120, 210, 330, 480, and 630 s of
      mixing. The coefficient of variation among 10 samples for each mixing time was
      used to measure mixer efficiency as determined by Cl concentration. A salt
      particle size x sample preparation x mixing time interaction was observed (P =
      0.04). Samples with 2,000- or 3,000-microm salt particle size (unground or
      ground) never reached the desired mixing efficiency of a 10% CV. Using 440-microm
      salt (unground or ground) or 730-microm salt particle sizes (ground) was
      necessary to accurately achieve a mixing efficiency of a <10% CV within 330 and
      630 s, respectively. Next, 180 weanling pigs (PIC, 6.31 +/- 0.84 kg of BW, 21 +/-
      3 d of age) were fed diets in 2 phases (d 0 to 14 and d 14 to 28). Treatments
      consisted of mixing diets for 0, 30, 60, 120, or 330 s (440-microm salt particle
      size). Samples were collected in the mixer, and then each bag of feed (22.5 kg)
      was labeled (first to last as-manufactured) and sampled to determine the mixing
      efficiency. An individual bag of feed was fed to a single pen of pigs, and when
      finished, the next sequential bag was used. As mixing time increased, mixer CV
      were 178, 38, 26, 21, and 5% for phase 1 and 172, 79, 60, 48, and 26% for phase
      2. As mixing time increased, bag CV values were 26, 20, 16, 11, and 7% for phase
      1 and 56, 45, 40, 33, and 12% for phase 2. From d 0 to 14, increasing mixing time
      increased ADG (linear, P < 0.01) and G:F (quadratic, P = 0.03). From d 0 to 28,
      increasing mixing time increased ADG (quadratic, P < 0.01) and G:F (linear, P =
      0.04). These data demonstrate that inadequate diet mixing (CV > 12%) reduces
      nursery pig performance.

PMID- 17431043
TI  - Effects of ractopamine supplementation on growth performance and carcass
      characteristics of feedlot steers differing in biological type.
AB  - Effects of ractopamine hydrochloride (RAC) supplementation on growth performance
      and carcass characteristics of feedlot steers differing in biological type were
      investigated using British, Continental crossbred, and Brahman crossbred calf-fed
      steers (n = 420). Steers of each type were weighed at reimplantation [British,
      mean BW = 375 kg (SD = 38 kg); Continental crossbred, mean BW = 379 kg (SD = 42
      kg); Brahman crossbred, mean BW = 340 (SD = 32 kg)] and sorted into 7 BW blocks,
      each block consisting of 2 pens (10 steers per pen) per type. Pens within a block
      x type subclass were randomly assigned to RAC treatments (0 or 200 mg x steer(-1)
      x d(-1) fed during the final 28 d of the finishing period). The type x RAC
      interaction did not affect (P > 0.05) any of the traits evaluated in this study.
      Feeding RAC improved (P = 0.001) ADG (1.50 vs. 1.73 +/- 0.09 kg) and G:F (0.145
      vs. 0.170 +/- 0.005), but did not affect (P = 0.48) DMI of steers. Dressing
      percentage, adjusted fat thickness, KPH percentage, and yield grade were not
      affected by RAC supplementation. Carcasses of steers fed RAC had heavier (P =
      0.01) HCW (359 vs. 365 +/- 4.9 kg), larger (P = 0.046) LM areas (81.7 vs. 84.0 +/
      1.1 cm(2)), and tended (P = 0.07) to have lower mean marbling scores (487 vs.
      477 +/- 5.2; Slight = 400, Small = 500) than did carcasses of control steers.
      Among the 3 biological types, Brahman crossbred steers had the lowest DMI and
      produced the lightest-weight carcasses that had the lowest mean marbling score (P
      < 0.05). Compared with Continental crossbred and Brahman crossbred steers,
      British steers produced carcasses with the greatest (P = 0.001) mean marbling
      scores. Continental crossbred steers had the heaviest BW and greatest dressing
      percentages and produced the heaviest carcasses with the largest LM areas (P <
      0.05) compared with British and Brahman crossbred steers. In the present study,
      28 d of supplementation with RAC at a dosage rate of 200 mg x steer(-1) x d(-1)
      elicited consistent responses in growth performance and carcass traits among 3
      diverse biological cattle types.

PMID- 17431044
TI  - Energy and nutrient digestibility in NutriDense corn and other cereal grains fed
      to growing pigs.
AB  - Two experiments were conducted to measure the energy and nutrient digestibilities
      in NutriDense corn and other cereal grains. An additional objective was to
      evaluate the effect of balancing diets with AA on the values measured for DE and
      ME of corn varieties. In Exp. 1, 6 growing pigs were fitted with a T-cannula in
      the distal ileum and allotted to a 6 x 6 Latin square design to measure apparent
      ileal digestibility (AID) and standardized ileal digestibility (SID) values for
      CP and AA in NutriDense corn, yellow dent corn, barley, wheat, and sorghum. Diets
      based on each of the 5 cereal grains were formulated, along with a N-free diet.
      Results of this experiment showed that the AID for most indispensable AA were
      greater (P < 0.05) in NutriDense corn and wheat than in the other cereal grains.
      The SID for Lys in NutriDense corn (77.6%) was greater (P < 0.05) than in yellow
      dent corn (68.5%), and sorghum (56.9%), but not different from wheat (75.1%) and
      barley (71.7%). The SID for Arg and Met in NutriDense corn also were greater (P <
      0.05) than in yellow dent corn (88.1 and 87.2% vs. 84.5 and 82.8%, respectively).
      For the remaining indispensable AA, no differences in SID between NutriDense corn
      and yellow dent corn were observed. For all AA, the lowest values (P < 0.05) for
      AID and SID were obtained for sorghum. If calculated as grams of standardized
      ileal digestible AA per kilogram of DM, concentrations of all indispensable AA in
      NutriDense corn were greater (P < 0.05) than in yellow dent corn, but barley and
      wheat had greater concentrations of most AA than yellow dent corn and NutriDense
      corn. In Exp. 2, 12 growing barrows were placed in metabolism cages, and the DE
      and ME of NutriDense corn and yellow dent corn were measured. Both grains were
      used in diets without or with crystalline AA supplementation. Each diet was fed
      to 6 pigs in a 2-period, changeover design. The DE and the ME in NutriDense corn
      (4,004 and 3,922 kcal/kg of DM, respectively) were greater (P < 0.01) than in
      yellow dent corn (3,878 and 3,799 kcal/kg of DM, respectively). Values for DE and
      ME were not affected by the addition of crystalline AA to the diets. It is
      concluded that NutriDense corn has a greater value than yellow dent corn in diet
      formulations due to increased concentrations of digestible, indispensable AA and
      energy. However, barley and wheat have greater concentrations, whereas sorghum
      has lower concentrations, of many digestible AA than NutriDense corn.

PMID- 17431045
TI  - Intramuscular fat deposition in principal muscles from twenty-four to thirty
      months of age using identical twins of Japanese Black steers.
AB  - The changes in i.m. fat deposition in the principal muscles [M. semitendinosus,
      M. semimembranosus, M. psoas major, M. latissimus dorsi, LM (7th to 8th and 10th
      to 11th thoracic vertebrae), and M. supraspinatus] from 24 to 30 mo of age were
      investigated using identical twins of Japanese Black steers. Four sets of
      identical twins of Japanese Black steers were used in this study. Animals were
      fattened from 10 to 24 or 30 mo of age for each pair of identical twins. Body
      weights of twin steers slaughtered at 24 and at 30 mo of age were similar at 10
      mo of age and thereafter up to 24 mo of age. The changes in serum concentration
      of vitamin A, glucose, total cholesterol, albumin, and total protein were similar
      in each pair of twins during the first fattening stage (10 to 24 mo). Fat
      contents of LM (7th to 8th thoracic vertebrae) at 24 and 30 mo of age were 37.0
      and 42.4%, respectively (P < 0.05). Moreover, in the principal muscles, except M.
      semimembranosus and M. supraspinatus, fat content at 30 mo of age was greater
      than at 24 mo of age (P < 0.05). The proportional increase in fat content from 24
      to 30 mo of age was greatest in M. semitendinosus (+58.7%) and least in M.
      supraspinatus (+6.1%). These results demonstrate that i.m. fat continues to
      increase after 24 mo of age, and the rates of i.m. fat deposition and the ages
      when i.m. fat is deposited are different for every muscle.

PMID- 17431046
TI  - Endocrine profiles of periparturient mares and their foals.
AB  - The aim of this study was to characterize concentrations of leptin, IGF-I, and
      thyroid stimulating hormone (TSH) in the blood serum of mares pre-and postpartum,
      in the milk serum of mares postpartum, and in the blood serum of their foals.
      Nine pregnant Quarter Horse mares and their offspring were used in this study.
      Once weekly between 1000 and 1200 h for 2 wk before their predicted parturition
      date, mares were weighed, assigned a BCS, and blood was sampled via jugular
      venipuncture. Within 2 h of parturition and before the foals nursed (d 0), blood
      samples were obtained from the mares and foals, and a milk sample was collected
      from the mares. Blood from the foals and blood and milk from the mares were
      collected again at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 12, 19, 26, 33, and 61
      d postpartum. Mares and foals also were weighed and assigned a BCS on d 0, 5, 12,
      19, 26, 33, and 61. Additionally, on d 5, 33, and 61, ultrasound images of fat
      depth and area of the LM immediately cranial to and parallel with the last rib on
      the left side of the foals were measured to characterize changes in fat depth and
      LM area over time. There were no changes in mare blood concentrations TSH (P =
      0.15), nor were there any changes in foal blood concentrations of leptin (P =
      0.54) or TSH (P = 0.10) during the trial period. Mare blood concentrations of IGF
      I tended to change over time (P = 0.07), whereas leptin changed over time (P <
      0.001), initially decreasing and then remaining relatively stable after d 5. Foal
      blood concentrations of IGF-I increased initially, peaked at d 19, and stabilized
      thereafter (P < 0.001). Milk concentrations of leptin and TSH were greatest on d
      0 and decreased over time (P < 0.007), reaching nadir concentrations at d 61.
      Milk concentrations of IGF-I also changed over time (P = 0.02), being greatest on
      d 0 and undetectable by d 12. There was no difference in BCS (P = 0.94) in mares
      over time, but there was a difference between pre- and postpartum BW (P < 0.001)
      due to foaling. However, no differences were detected in pre- (P = 0.70) or
      postpartum BW (P = 0.76) of mares over time. Mean ultrasonic fat depth and LM
      area increased (P < 0.04) as the foals aged, as did BCS and BW (P < 0.001).
      Recognizing changes in metabolic hormones surrounding the time of parturition in
      the mare and foal provides a basis for further determination of the role, if any,
      these hormones play in the milk, as well as in the neonate.

PMID- 17431047
TI  - Correlation between reproductive status and steady-state messenger ribonucleic
      acid levels of the Myxovirus resistance gene, MX2, in peripheral blood leukocytes
      of dairy heifers.
AB  - The objectives of the current study were to evaluate the correlation between
      reproductive status and steady-state levels of Myxovirus resistance gene (MX2)
      mRNA in peripheral blood leukocytes (PBL) of dairy heifers and the reliability of
      using change in MX2 messenger RNA (mRNA) for identification of nonpregnant
      heifers 18 to 19 d after AI. Holstein heifers (n = 266), 13 +/- 1 mo of age, were
      assigned randomly to be inseminated (BRED; n = 214) or not (NONBRED; n = 52).
      Estrous cycles of all heifers were synchronized with an intravaginal insert
      containing progesterone for 7 d. At insert removal, heifers received an injection
      of PGF2alpha. Heifers in the BRED group were inseminated on detection of estrus
      or at a fixed time, 72 h after insert removal concomitant with a GnRH treatment.
      Heifers in the NONBRED group received an injection of GnRH 48 h after insert
      removal. Blood samples collected on d 0 (d of AI or estrus) and 18 were used to
      determine steady-state levels of MX2 mRNA. Samples collected on d 0, 7, 14, and
      21 were analyzed for progesterone concentration. Pregnancy was determined
      retrospectively by progesterone concentration on d 21 and was diagnosed at 30 +/-
      1 and 60 +/- 3 d after AI. The fold change in levels of MX2 mRNA from d 0 to 18
      was greater for heifers classified and diagnosed as pregnant on d 21 (P < 0.05)
      and 30 +/- 1 (P < 0.05) and 60 +/- 3 (P < 0.05) d after AI compared with
      nonpregnant (bred but not pregnant) and NONBRED heifers. Heifers that experienced
      pregnancy loss from 21 to 30 +/- 1 (P = 0.11) or 21 to 60 +/- 3 (P = 0.08) d of
      gestation tended to have smaller fold increases in MX2 mRNA expression than those
      that maintained pregnancy. The sensitivity (range 57.1 to 65.6%) and negative
      predictive values (range 47.9 to 57.1%) of determining reproductive status on d
      18 according to the change in the level of MX2 mRNA expression in PBL were low,
      and the correlation between diagnosis of pregnancy by fold change in MX2 mRNA
      expression and other methods was small (r = 0.20 to 0.36). The current study
      indicates that increased expression of MX2 mRNA in PBL is related to pregnancy
      approximately 21, 30, and 60 d after AI in dairy heifers and that losses that
      occurred later in pregnancy were associated with lower fold increases in MX2
      mRNA. However, using the change in MX2 mRNA expression was not a reliable method
      for diagnosis of pregnancy at 18 d after AI because of the low sensitivity and
      negative predictive value.

PMID- 17431048
TI  - Association of single nucleotide polymorphisms in the leptin gene with body
      weight and backfat growth curve parameters for beef cattle.
AB  - Previous research has identified differences in carcass characteristics across
      SNP in the bovine leptin gene at slaughter, but before feedlot operators
      implement selection and sorting strategies, more information is needed to
      determine how carcass characteristics change over time. The objective of this
      study was to investigate the effect of 2 leptin SNP on growth curve parameters
      for BW and backfat. Two SNP (UASMS2 and R25C) were genotyped on 1,653 cross-bred
      steers and heifers in a commercial feedlot. Up to 4 serial measures of BW and
      ultrasound estimates of backfat thickness were taken for each animal from the
      time of placement on feed to slaughter. The measures were used to estimate growth
      models that describe changes in BW and backfat thickness as a function of days on
      feed. Data analysis was carried out by estimating nonlinear mixed models to
      determine the individual and joint effect of each SNP on growth curve parameters.
      Brody growth curves were fit to the BW data. Variations in the R25C SNP did not
      significantly affect growth parameters individually or in combination with the
      UASMS2 SNP. Variations in the UASMS2 SNP were significant in Brody growth curve
      parameters for BW growth (P < 0.001). The genotype UASMS2-CC was the heaviest at
      the beginning of the feeding period and exhibited the largest asymptotic mature
      BW, but UASMS2-TT cattle exhibited the fastest rate of BW growth. A modified
      power function was fit to the serial ultrasound backfat measures. Models that
      included the combined effect of the R25C and UASMS2 SNP provided the best fit to
      the data. Genotypes differed significantly in power function parameters for
      backfat growth (P < 0.001). The R25C-CC/UASMS2-TT cattle had the smallest backfat
      thickness at placement. The genotype R25C-CC/UASMS2-TT exhibited the fastest
      backfat growth rate, whereas backfat in R25C-CC/UASMS2-CC cattle grew at the
      slowest rate. The association between leptin genotype and growth in BW and
      backfat presents opportunities to identify genetically distinct cattle and to
      differentially optimize feeding times accordingly.

PMID- 17431049
TI  - Corn oil supplementation to steers grazing endophyte-free tall fescue. II.
      Effects on longissimus muscle and subcutaneous adipose fatty acid composition and
      stearoyl-CoA desaturase activity and expression.
AB  - Eighteen steers were used to evaluate the effect of supplemental corn oil level
      to steers grazing endophyte-free tall fescue on fatty acid composition of LM,
      stearoyl CoA desaturase (SCD) activity and expression as well as cellularity in
      s.c. adipose. Corn oil was supplemented (g/kg of BW) at 0 (none), 0.75 (medium),
      and 1.5 (high). Cottonseed hulls were used as a carrier for the corn oil and were
      supplemented according to pasture availability (0.7 to 1% of BW). Steers were
      finished on a rotationally grazed, tall fescue pasture for 116 d. Fatty acid
      composition of LM, s.c. adipose, and diet was determined by GLC. Total linoleic
      acid intake increased linearly (P < 0.01) with corn oil supplementation (90.7,
      265.1, and 406.7 g in none, medium, and high, respectively). Oil supplementation
      linearly reduced (P < 0.05) myristic, palmitic, and linolenic acid percentage in
      LM and s.c. adipose. Vaccenic acid (C18:1 t11; VA) percentage was 46 and 32%
      greater (linear, P = 0.02; quadratic, P = 0.01) for medium and high,
      respectively, than none, regardless of tissue. Effect of oil supplementation on
      CLA cis-9, trans-11 was affected by type of adipose tissue (P < 0.01). In the LM,
      CLA cis-9, trans-11 isomer was 25% greater for medium than for none and
      intermediate for high, whereas CLA cis-9, trans-11 CLA isomer was 48 and 33%
      greater in s.c. adipose tissue for medium and high than for none, respectively.
      Corn oil linearly increased (P </= 0.01) trans-10 octadecenoic acid and CLA trans
      10, cis-12; however, values were low (<0.35 and <0.035% of total fatty acids,
      respectively). Oil supplementation did not change (P > 0.05) the percentage of
      total SFA, MUFA, or PUFA but linearly increased (P = 0.03) n-6:n-3 ratio from 2.4
      to 2.9 in none and high, respectively. Among tissues, total SFA and MUFA were
      greater in s.c. adipose than LM, whereas total PUFA, n-6, and n-3 fatty acids and
      the n-6:n-3 ratio were lower. Trans-10 octadecenoic acid, VA, and CLA trans-10,
      cis-12 were greater (P < 0.01) in s.c. adipose than in LM. Oil supplementation
      did not alter (P > 0.05) stearoyl CoA desaturase activity or mRNA expression.
      Corn oil supplementation to grazing steers reduced the percentages of highly
      atherogenic fatty acids (myristic and palmitic acids) and increased the
      percentages of antiatherogenic and anticarcinogenic fatty acids (VA and cis-9,
      trans-11 CLA).

PMID- 17431050
TI  - Influence of ruminal and postruminal carbohydrate infusion on visceral organ mass
      and adipose tissue accretion in growing beef steers.
AB  - Forty crossbred beef steers (243 +/- 2 kg of BW) with ruminal and abomasal
      infusion catheters were used to test 2 hypotheses: 1) visceral mass is responsive
      to energy input and site of carbohydrate (CHO) infusion and 2) rate and site of
      adipose accretion are dependent on site of CHO infusion and complexity.
      Treatments included a pelleted, forage-based, basal diet fed at 161 (LI) or 214
      (HI) kcal of ME/(kg of BW(0.75) x d), LI plus ruminal (R-SH) or abomasal (A-SH)
      infusion of a partial starch hydrolysate (SH), and LI plus abomasal infusion of
      glucose (A-G). The basal diet was fed in 12 equal portions daily at 2-h
      intervals, with starch and glucose infused over a 22-h period at rates of 12.6
      and 14.4 g/(kg of BW(0.75) x d). After 35 d of infusion, steers were slaughtered;
      and visceral organ and adipose mass, subcutaneous adipose thickness over the 5th
      and 12th rib, and LM intramuscular fat concentration were determined. Total
      intake energy (IE) increased (P = 0.0001) with ME intake. Dietary IE was similar
      between LI and CHO treatments, but total IE increased (P < 0.001) with CHO
      infusion. Greater dietary ME intake and CHO infusion increased or tended (P < or
      = 0.09) to increase final BW and HCW. As a percentage of empty BW, total stomach
      complex, rumen, omasum, liver, pancreas, and kidney weights were greater (P < or
      = 0.05) for HI vs. LI. Stomach complex, rumen, pancreas, and kidney weights as a
      percentage of empty BW were greater (P < or = 0.05) for R-SH vs. A-SH. Compared
      with ASH, A-G increased (P < or = 0.02) total and mucosal weights from the 10-cm
      sections of the ileum. Increases in rumen mass were associated with no change or
      an increase in rumen total and mucosal DNA concentrations. Greater dietary ME
      tended (P = 0.06) to increase subcutaneous fat thickness at the 5th rib but did
      not affect alimentary adipose accretion on an empty BW basis. Omental and total
      alimentary adipose weights were increased (P < or = 0.04) by A-G compared with A
      SH. Although SH infusion did not alter adiposity, there was a consistent
      numerical pattern in total alimentary and subcutaneous fat depots with CHO
      infusion (A-G > ASH > R-SH). Our findings demonstrate that increasing ruminal CHO
      supply results in a disproportionate increase in rumen mass, whereas increasing
      small intestinal CHO supply does not alter gastrointestinal organ mass. Small
      intestinal energy in the form of glucose resulted in greater adipose accretion,
      particularly the omental depot.

PMID- 17431052
TI  - Genetic parameters for measures of the efficiency of gain of boars and the
      genetic relationships with its component traits in Duroc pigs.
AB  - Genetic parameters for the efficiency of gain traits on 380 boars and the genetic
      relationships with component traits were estimated in 1,642 pigs (380 boars, 868
      gilts, and 394 barrows) in 7 generations of a Duroc population. The efficiency of
      gain traits included the feed conversion ratio (FCR) and residual feed intake
      (RFI) and their component traits, ADG, metabolic BW (MWT), and daily feed intake
      (FI). The RFI was calculated as the difference between the actual and expected
      FI. The expected FI was predicted by the nutritional requirement and by the
      residual of phenotypic (RFI(phe)) and genetic (RFI(gen)) regressions from the
      multivariate analysis for FI on MWT and ADG. The means for RFI(phe) and RFI(gen)
      were close to zero, and the mean for nutritional RFI was negative (-0.11 kg/d).
      The traits studied were moderately heritable (ranging from 0.27 to 0.53). The
      genetic and phenotypic correlations between ADG and FI were moderate to high,
      whereas the genetic correlation between MWT and FI was moderate, and the
      phenotypic correlation between them was low. The corresponding correlations
      between RFI(phe) and RFI(gen) were > 0.95, implying that they can be regarded as
      the same trait. The genetic and phenotypic correlations of FCR with measures of
      RFI were high but lower than unity. The RFI(phe) was phenotypically independent
      of its component traits, MWT (r(p) = 0.01) and ADG (r(p) = 0.03). The RFI(gen)
      was genetically independent of MWT (r(g) = -0.04), whereas there was a weak
      genetic relationship (r(g) = 0.15) between RFI(gen) and ADG. Residual FI was more
      heritable than FCR, and the genetic and phenotypic correlations of RFI(phe) and
      RFI(gen) with FI were positive and stronger than that of FCR with FI. These
      results provide evidence that RFI(phe) or RFI(gen) should be included in breeding
      programs for Duroc pigs to make genetic improvement in the efficiency of gain.

PMID- 17431051
TI  - Effects of heifer finishing implants on beef carcass traits and longissimus
      tenderness.
AB  - Effects of finishing implants on heifer carcass characteristics and LM Warner
      Bratzler shear force (WBSF) were investigated using commercially fed Continental
      x British heifers (n = 500). Heifers were blocked by initial BW (block 1, BW > or
      = 340 kg; block 2, BW < 340 kg) and assigned randomly to 12 treatments that
      utilized 0, 1, or 2 finishing implants to deliver cumulative dosages of
      trenbolone acetate (TBA) and estradiol 17-beta (E2) ranging from 0 to 400 mg of
      TBA and 0 to 40 mg of E2 during the finishing period. Heifers in blocks 1 and 2
      were slaughtered after 135 and 149 d on feed, respectively. At these endpoints,
      the treatment groups did not differ (P > 0.05) in adjusted fat thickness or
      predicted percentage of empty body fat. Compared with a nonimplanted control,
      implanting heifers once during finishing increased (P = 0.025) HCW by an average
      of 7.9 kg without affecting the mean marbling score, the percentage of carcasses
      grading Choice and Prime, or LM WBSF values. Compared with the use of 1 implant,
      the use of 2 finishing implants resulted in an additional increase (P = 0.008) in
      HCW of 6.0 kg. Reimplanting also increased (P < 0.001) LM area, reduced (P =
      0.024) the percentage of KPH, and improved (P = 0.004) mean yield grade. However,
      reimplanted heifers produced a lower (P = 0.044) percentage of carcasses grading
      Choice and Prime and LM steaks with greater (P < 0.05) WBSF values at all
      postmortem aging times compared with heifers that were implanted once. Among
      heifers receiving 2 implants, mean 14-d LM WBSF increased linearly (P < 0.05) as
      the cumulative, combined dosage of E2 plus TBA increased. Heifers implanted with
      a combination of E2 plus TBA had larger (P = 0.046) LM areas, lower (P = 0.004)
      mean marbling scores, and greater LM WBSF values after 3 d (P = 0.001), 7 d (P =
      0.001), 14 d (P = 0.003), and 21 d (P = 0.045) of postmortem aging than did
      heifers implanted with TBA alone. Heifers that received combination implants
      containing both E2 and TBA also produced fewer (P = 0.005) carcasses with
      marbling scores of modest or greater compared with heifers that received single
      ingredient implants containing TBA alone. Implant treatment effects on LM WBSF
      gradually diminished as the length of the postmortem aging period increased.
      Postmortem aging periods of 14 to 28 d were effective for mitigating the
      detrimental effects of mild or moderately aggressive heifer implant programs on
      the predicted consumer acceptability of LM steaks.

PMID- 17431053
TI  - Heart fatty acid binding protein is upregulated during porcine adipocyte
      development.
AB  - Heart fatty acid binding protein (H-FABP) has been associated with intramuscular
      fat content in pigs. In the current study, we showed that expression of H-FABP
      mRNA in adipose tissue of adult pigs was 8.5% of that in heart and 30% of that in
      skeletal muscle, and that H-FABP mRNA level was more than 10% of that of
      adipocyte fatty acid binding protein mRNA in adipose tissue. Levels of H-FABP
      mRNA reached a maximum in adipose tissue from 7-d neonates, with no further
      increase in the adult. Also, H-FABP mRNA was induced during adipogenic
      differentiation of stromal-vascular cells derived from adipose tissue and
      skeletal muscle. In conclusion, H-FABP may play a role in adipose tissue
      development and function in the pig.

PMID- 17431054
TI  - Consequence of muscle hypertrophy on characteristics of Pectoralis major muscle
      and breast meat quality of broiler chickens.
AB  - The structural and metabolic characteristics of the pectoralis major (P. major)
      muscle (i.e., breast muscle) and the quality of the resulting meat were studied
      in relation to breast muscle fiber development in broiler chickens. Six hundred
      birds originating from a commercial, grand parental, male heavy line (Hubbard
      Europe, Chateaubourg, France) were kept under conventional breeding methods until
      their usual marketing age of 6 wk. For all birds, the plasma creatine kinase
      activity and the P. major muscle fiber cross-sectional area (CSA), glycolytic
      potential, lactate content, pH at 15 min postmortem, as well as the ultimate pH,
      CIELAB color parameters [lightness (L*), redness (a*), and yellowness (b*)], and
      drip loss of breast meat, were measured. Increased breast weight and yield were
      associated with increased fiber CSA, reduced muscle glycolytic potential, and
      reduced lactate content at 15 min postmortem. Therefore, P. major muscle
      exhibiting larger fiber CSA exhibited greater pH at 15 min postmortem and
      ultimate pH, produced breast meat with lower L* and reduced drip loss, and was
      potentially better adapted to further processing than muscle exhibiting small
      fiber CSA.

PMID- 17431055
TI  - Traumatic axonal injury: atlas of major pathways.

PMID- 17431056
TI  - Neuropsychiatric complications of traumatic brain injury: a critical review of
      the literature (a report by the ANPA Committee on Research).
AB  - Psychiatric disorders frequently complicate recovery and rehabilitation from
      traumatic brain injury (TBI). This study reviews the literature from 1978 to 2006
      on psychosis, depression, posttraumatic stress disorder, mania, and aggression
      following nonpenetrating TBI. The studies were reviewed using the American
      Academy of Neurology's criteria for classification of articles on diagnostic
      methods. No studies were found to be Class I or II. Of the 66 studies reviewed,
      the majority were Class IV. There are significant gaps in the literature on post
      TBI psychiatric conditions with respect to nosology, epidemiology, and risk
      factors. Larger multicenter prospective studies using standardized diagnostic
      instruments are needed to further clarify the nosology, risk factors, and
      clinical course of these disorders. Specific directions for research are
      provided.

PMID- 17431057
TI  - Association between facial emotion recognition and odor identification in
      schizophrenia.
AB  - The authors examine facial emotion recognition and unirhinal olfactory
      performance in 19 schizophrenia patients and 14 comparison subjects. In patients,
      right nostril odor identification performance was positively related to overall
      emotion recognition accuracy, specifically, sad facial expressions. Olfactory and
      emotion recognition abilities appear significantly linked in schizophrenia.

PMID- 17431058
TI  - Verbal memory retrieval deficits associated with untreated hypothyroidism.
AB  - The effects of inadequate thyroid hormone availability to the brain on adult
      cognitive function are poorly understood. This study assessed the effects of
      hypothyroidism on cognitive function using a standard neuropsychological battery
      in 14 patients suffering from untreated hypothyroidism and complaining of
      subjective cognitive difficulties in comparison with 10 age-matched healthy
      comparison subjects. Significant differences between groups were limited to
      verbal memory retrieval as measured by the California Verbal Learning Test
      (CVLT). On short delay free recall, long delay free recall, and long delay cued
      recall, significant differences remained between groups despite the limited
      statistical power of this study. There were no significant results found between
      groups on attentional or nonverbal tasks. Results suggest that hypothyroid
      related memory deficits are not attributable to an attentional deficit but rather
      to specific retrieval deficits.

PMID- 17431059
TI  - Brain response correlates of decisional capacity in schizophrenia: a preliminary
      FMRI study.
AB  - The capacity of schizophrenia patients to make decisions regarding research
      consent relates to neurocognition, but the exact nature of the relationship is
      unclear. The authors examined the correlation of scores on the MacArthur
      Competence Assessment Tool for Clinical Research with functional magnetic
      resonance imaging brain response during a verbal learning task. Understanding of
      a consent form correlated with activation of the right hippocampus during verbal
      learning and with brain response in a large area that included the bilateral
      parahippocampus, cerebellum, and thalamus. Reasoning scores were not
      significantly related to brain activation. Understanding deficits during informed
      consent relates to particular brain abnormalities among schizophrenia patients.

PMID- 17431060
TI  - Neurological soft signs in schizophrenia patients with obsessive-compulsive
      disorder.
AB  - Obsessive-compulsive disorder is a prevalent and clinically significant
      phenomenon in schizophrenia patients. Both schizophrenia and obsessive-compulsive
      disorder (OCD) are considered to be neurodevelopmental disorders sharing
      dysfunctional frontal-subcortical circuitry. Using the Neurological Evaluation
      Scale (NES), the authors assessed neurological soft signs in 59 patients who met
      DSM-IV criteria for both schizophrenia and OCD. The two schizophrenia groups
      (with and without OCD) scored higher than the comparison group but did not
      significantly differ from one another on any of the NES subscales. The first
      episode patients in both groups scored similarly to patients with repeated
      hospitalizations on all NES subscales. Notably, the OCD patients scored similarly
      to the two schizophrenia groups on the NES motor sequencing subscale. The
      author's findings support the notion that neurological soft signs are independent
      markers of brain dysfunction detectable early in the course of schizophrenia.
      However, they are of limited value as a putative endophenotype in a search for
      specific etiological mechanisms underlying a schizo-obsessive subgroup of
      schizophrenia.

PMID- 17431061
TI  - An exploratory study of diagnostic criteria for delirium in older medical
      inpatients.
AB  - The poor prognosis of delirium in older medical inpatients has generated
      controversy about the diagnostic criteria for delirium in this population. The
      goal of the present study was to explore the presenting symptoms of delirium
      among older medical inpatients who did or did not recover from delirium. Patients
      65 years or older admitted from the emergency department to medical services were
      screened with the Confusion Assessment Method (CAM). Patients with delirium were
      assessed at enrollment, several times during the first week, then weekly for 4
      weeks using the Delirium Index (DI). Measures at baseline included demographics,
      dementia and severity of physical illness. Recovery was defined as a decline of
      three points or more on the DI and a final DI score of less than 5 or 4 points in
      patients with or without dementia, respectively. Of 290 patients who met DSM-IV
      criteria for delirium, 65 recovered and 225 did not. Three symptoms (orientation
      to person, hyperactivity, and inattention) were associated with recovery from
      delirium in older medical inpatients. These results suggest it may be necessary
      to place increased emphasis on these presenting symptoms when diagnosing delirium
      in this population.

PMID- 17431063
TI  - Influence of diazepam on clinically designed FMRI.
AB  - The authors investigated the effect of diazepam on clinically relevant measures
      from functional magnetic resonance imaging (fMRI) examinations. Twenty volunteers
      were scanned twice. Using a double-blind randomized study design, the volunteers
      received placebo on one occasion, and on the other, 5 mg of diazepam. Three
      functional tests were used: motor, word generation, and working memory. Images
      were analyzed individually for each subject and the number of activated voxels
      and the laterality index were calculated. No significant effects related to the
      drug were detected. In contrast, the motor and working memory tasks showed a
      significant decrease in the number of activated voxels between Sessions 1 and 2,
      independently of diazepam administration. These results indicate that diazepam
      may be administered for premedication prior to fMRI investigations.

PMID- 17431062
TI  - HIV proviral DNA associated with decreased neuropsychological function.
AB  - The authors previously found a strong association between elevated HIV proviral
      DNA (HIV DNA) and a diagnosis of HIV-1-associated dementia (HAD) vs. normal
      cognition. It is unclear whether HIV DNA globally affects the diagnosis of HAD or
      whether the effect is limited to individual neuropsychological deficits. This
      exploratory study examined baseline HIV DNA and its association with individual
      neuropsychological deficits. HIV DNA was significantly associated with baseline
      neuropsychological deficits independent of age, ethnicity, IQ, and plasma HIV-1
      RNA levels. However, HIV DNA did not predict future changes in neuropsychological
      deficits. The data suggest that HIV DNA and neuropsychological deficits may co
      vary over time.

PMID- 17431064
TI  - Performance on the Mini-Mental State Examination and Mattis Dementia Rating Scale
      among older American Indians.
AB  - Optimal methods for assessing cognitive impairment among older American Indians
      have not been established. This study sought to examine the cultural relevance
      and performance of two common cognitive screening measures, the Mini-Mental State
      Examination (MMSE) and Mattis Dementia Rating Scale (MDRS), in one American
      Indian population. One hundred forty American Indians ages 60 to 89 were
      assessed; nearly 11% scored more than 2 standard deviation points below
      performance expectations on the MMSE, as did 27% to 81% on the MDRS. Complex
      relationships were found between gender, health conditions (with possible effects
      on cognitive functioning), and MMSE and MDRS scores. The authors discuss
      implications and future directions.

PMID- 17431065
TI  - Antidepressant effects of high and low frequency repetitive transcranial magnetic
      stimulation to the dorsolateral prefrontal cortex: a double-blind, randomized,
      placebo-controlled trial.
AB  - Repetitive transcranial magnetic stimulation (rTMS) has antidepressant effects in
      patients with major depressive disorder. The mechanisms of action and optimal
      stimulation parameters remain unclear. To test the hypothesis that rTMS exerts
      antidepressant effects either by enhancing left dorsolateral prefrontal cortex
      (DLPFC) excitability or by decreasing right DLPFC excitability, the authors
      studied 45 patients with unipolar recurrent major depressive disorder in a double
      blind, randomized, parallel group, sham-controlled trial. Patients were
      randomized to receive 1 Hz or 10 Hz rTMS to the left DLPFC, 1 Hz to the right
      DLPFC or sham TMS. Left 10 Hz and right 1 Hz rTMS showed similar significant
      antidepressant effects. Other parameters led to no significant antidepressant
      effects.

PMID- 17431067
TI  - ECT in patients with intracranial masses.
AB  - The authors describe the electroconvulsive therapy (ECT) treatment of seven
      patients who had intracranial masses or mass effect and one patient who was
      status post mass resection. None suffered any neurological deterioration during
      ECT. They provide recommendations for clinical practice with such patients.

PMID- 17431066
TI  - Exaggerated crying and tremor with a cerebellar cyst.
AB  - The authors describe clinical, neuropsychological, and neuroimaging findings in a
      70-year-old man with a cystic lesion in the midline cerebellum. He presented with
      pathological crying in parallel to a worsening of his ataxia. This report
      suggests a role for the cerebellum in the regulation of emotional expression.

PMID- 17431068
TI  - A rare case of epilepsy in a 16-year-old girl with fallot tetralogy attributed to
      CNS heterotopia and pachygyria.

PMID- 17431069
TI  - Mania as a possible prodrome to dementia.

PMID- 17431070
TI  - A comment on "exertion" after sports-related concussion.

PMID- 17431071
TI  - Possible delayed speech acquisition with clozapine therapy during pregnancy and
      lactation.

PMID- 17431072
TI  - Is there a role for valproic acid in the treatment of catatonia?

PMID- 17431073
TI  - Stimulating research: a prospective, randomized, double-blind, sham-controlled
      study of slow transcranial magnetic stimulation in depressed bipolar patients.

PMID- 17431074
TI  - Hereditary hemorrhagic telangiectasia and psychopathology.

PMID- 17431075
TI  - Posttraumatic parieto-occipital epilepsy.

PMID- 17431076
TI  - Patau syndrome.

PMID- 17431077
TI  - Pisa syndrome resolved after switching to olanzapine.

PMID- 17431078
TI  - Prader-Willi syndrome.

PMID- 17431079
TI  - Association of familial ataxia and restless legs syndrome.

PMID- 17431080
TI  - Does aripiprazole have a role in treating cognitive impairment in Parkinson's
      disease?

PMID- 17431081
TI  - Substrate source utilization during moderate intensity exercise with glucose
      ingestion in Type 1 diabetic patients.
AB  - Substrate oxidation and the respective contributions of exogenous glucose,
      glucose released from the liver, and muscle glycogen oxidation were measured by
      indirect respiratory calorimetry combined with tracer technique in eight control
      subjects and eight diabetic patients (5 men and 3 women in both groups) of
      similar age, height, body mass, and maximal oxygen uptake, over a 60-min exercise
      period on cycle ergometer at 50.8% (SD 4.0) maximal oxygen uptake [131.0 W (SD
      38.2)]. The subjects and patients ingested a breakfast (containing approximately
      80 g of carbohydrates) 3 h before and 30 g of glucose (labeled with 13C) 15 min
      before the beginning of exercise. The diabetic patients also received their usual
      insulin dose [Humalog = 9.1 U (SD 0.9); Humulin N = 13.9 U (SD 4.4)] immediately
      before the breakfast. Over the last 30 min of exercise, the oxidation of
      carbohydrate [1.32 g/min (SD 0.48) and 1.42 g/min (SD 0.63)] and fat [0.33 g/min
      (SD 0.10) and 0.30 g/min (SD 0.10)] and their contribution to the energy yield
      were not significantly different in the control subjects and diabetic patients.
      Exogenous glucose oxidation was also not significantly different in the control
      subjects and diabetic patients [6.3 g/30 min (SD 1.3) and 5.2 g/30 min (SD 1.6),
      respectively]. In contrast, the oxidation of plasma glucose and oxidation of
      glucose released from the liver were significantly lower in the diabetic patients
      than in control subjects [14.5 g/30 min (SD 4.3) and 9.3 g/30 min (SD 2.8) vs.
      27.9 g/30 min (SD 13.3) and 21.6 g/30 min (SD 12.8), respectively], whereas that
      of muscle glycogen was significantly higher [28.1 g/30 min (SD 15.5) vs. 11.6
      g/30 min (SD 8.1)]. These data indicate that, compared with control subjects, in
      diabetic patients fed glucose before exercise, substrate oxidation and exogenous
      glucose oxidation overall are similar but plasma glucose oxidation is lower; this
      is associated with a compensatory higher utilization of muscle glycogen.

PMID- 17431082
TI  - Effects of acute hypoxia on cerebral and muscle oxygenation during incremental
      exercise.
AB  - To determine if fatigue at maximal aerobic power output was associated with a
      critical decrease in cerebral oxygenation, 13 male cyclists performed incremental
      maximal exercise tests (25 W/min ramp) under normoxic (Norm: 21% Fi(O2)) and
      acute hypoxic (Hypox: 12% Fi(O2)) conditions. Near-infrared spectroscopy (NIRS)
      was used to monitor concentration (microM) changes of oxy- and deoxyhemoglobin
      (Delta[O2Hb], Delta[HHb]) in the left vastus lateralis muscle and frontal
      cerebral cortex. Changes in total Hb were calculated (Delta[THb] = Delta[O2Hb] +
      Delta[HHb]) and used as an index of change in regional blood volume. Repeated
      measures ANOVA were performed across treatments and work rates (alpha = 0.05).
      During Norm, cerebral oxygenation rose between 25 and 75% peak power output
      {Power(peak); increased (inc) Delta[O2Hb], inc. Delta[HHb], inc. Delta[THb]}, but
      fell from 75 to 100% Power(peak) {decreased (dec) Delta[O2Hb], inc. Delta[HHb],
      no change Delta[THb]}. In contrast, during Hypox, cerebral oxygenation dropped
      progressively across all work rates (dec. Delta[O2Hb], inc. Delta[HHb]), whereas
      Delta[THb] again rose up to 75% Power(peak) and remained constant thereafter.
      Changes in cerebral oxygenation during Hypox were larger than Norm. In muscle,
      oxygenation decreased progressively throughout exercise in both Norm and Hypox
      (dec. Delta[O2Hb], inc. Delta [HHb], inc. Delta[THb]), although Delta[O2Hb] was
      unchanged between 75 and 100% Power peak. Changes in muscle oxygenation were also
      greater in Hypox compared with Norm. On the basis of these findings, it is
      unlikely that changes in cerebral oxygenation limit incremental exercise
      performance in normoxia, yet it is possible that such changes play a more pivotal
      role in hypoxia.

PMID- 17431083
TI  - Electromechanical stimulation ameliorates inactivity-induced adaptations in the
      medial gastrocnemius of adult rats.
AB  - The efficacy of high-load, short-duration isometric contractions, delivered as
      one vs. two sessions per day, on blunting inactivity-induced adaptations in the
      medial gastrocnemius (MG) were compared. Adult rats were assigned to a control
      (Con) or spinal cord-isolated (SI) group where one limb was stimulated (SI-Stim)
      while the other served as a SI control (SI-C). One bout of stimulation (BION
      microstimulator) consisted of a 100-Hz, 1-s stimulus, delivered every 30 s for 5
      min with a 5-min rest period. This bout was repeated six times consecutively (SI
      Stim1) or with a 9-h rest interval after the third bout (SI-Stim2) for 30
      consecutive days. MG weights (relative to body weight) were 63, 72, and 79% of
      Con in SI-C, SI-Stim1, and SI-Stim2, respectively. Mean fiber size was 56%
      smaller in SI-C than in Con, and it was 19 and 31% larger in SI-Stim1 and SI
      Stim2, respectively, compared with SI-C. Maximum tetanic tension was 42, 60, and
      73% of Con in SI-C, SI-Stim1, and SI-Stim2, respectively. Specific tension was
      77% of Con in SI-C, and at Con levels in both SI-Stim groups. SI increased the
      percent IIb myosin heavy chain composition (from 49 to 77%) and IIb+ fibers (from
      63 to 79%): these adaptations were prevented by both Stim paradigms. These
      results demonstrate that 1) brief periods of high-load isometric contractions are
      effective in reducing inactivity-induced atrophy, functional deficits, and
      phenotypic adaptations in a fast hindlimb extensor, and 2) the same amount of
      stimulation distributed in two compared with one session per day is more
      effective in ameliorating inactivity-related adaptations.

PMID- 17431084
TI  - Relative systolic dysfunction in female spontaneously hypertensive rat
      myocardium.
AB  - Hypertension and exercise independently induce left ventricular (LV) remodeling
      and alter LV function. The purpose of this study was to determine systolic and
      diastolic LV pressure-volume relationships (LV-PV) in spontaneously hypertensive
      rats (SHR) with and without LV hypertrophy, and to determine whether 6 mo of
      exercise training modified the LV-PV in SHR. Four-month-old female SHR (n = 20),
      were assigned to a sedentary (SHR-SED) or treadmill-trained (SHR-TRD) group
      (approximately 60% peak O2 consumption, 5 days/wk, 6 mo), while age-matched
      female Wistar-Kyoto rats (WKY; n = 13) served as normotensive controls. The LV-PV
      was determined using a Langendorff isolated heart preparation at 4 (no
      hypertrophy: WKY, n = 5; SHR, n = 5) and 10 mo of age (hypertrophy: WKY, n = 8;
      SHR-SED, n = 8; SHR-TRD, n = 7). At 4 mo, the LV-PV in SHR was similar to that
      observed in WKY controls. However, at 10 mo of age, a rightward shift in the LV
      PV occurred in SHR. Exercise training did not alter the extent of the shift in
      the LV-PV relative to SHR-SED. Relative systolic function, i.e., relative
      systolic elastance, was approximately 50% lower in SHR than WKY at 10 mo of age
      (P < 0.05). Doppler-derived LV filling parameters [early wave (E), atrial wave
      (A), and the E/A ratio] were similar between groups. LV capacitance was increased
      in SHR at 10 mo (P < 0.05), whereas LV diastolic chamber stiffness was similar
      between groups at 10 mo. Hypertrophic remodeling at 10 mo of age in female SHR is
      manifest with relative systolic decompensation and normal LV diastolic function.
      Exercise training did not alter the LV-PV in SHR.

PMID- 17431085
TI  - Caspase inhibition reduces cardiac myocyte dyshomeostasis and improves cardiac
      contractile function after major burn injury.
AB  - In the heart, thermal injury activates a group of intracellular cysteine
      proteases known as caspases, which have been suggested to contribute to myocyte
      inflammation and dyshomeostasis. In this study, Sprague-Dawley rats were given
      either a third-degree burn over 40% total body surface area plus conventional
      fluid resuscitation or sham burn injury. Experimental groups included 1) sham
      burn given vehicle, 400 microl DMSO; 2) sham burn given Q-VD-OPh (6 mg/kg), a
      highly specific and stable caspase inhibitor, 24 and 1 h prior to sham burn; 3)
      burn given vehicle, DMSO as above; 4) burn given Q-VD-OPh (6 mg/kg) 24 and 1 h
      prior to burn. Twenty-four hours postburn, hearts were harvested and studied with
      regard to myocardial intracellular sodium concentration, intracellular pH, ATP,
      and phosphocreatine (23Na/31P nuclear magnetic resonance); myocardial caspase-1, 
      3,and -8 expression; myocyte Na+ (fluorescent indicator, sodium-binding
      benzofurzan isophthalate); myocyte secretion of TNF-alpha, IL-1beta, IL-6, and IL
      10; and myocardial performance (Langendorff). Burn injury treated with vehicle
      alone produced increased myocardial expression of caspase-1, -3, and -8, myocyte
      Na+ loading, cytokine secretion, and myocardial contractile depression; cellular
      pH, ATP, and phosphocreatine were stable. Q-VD-OPh treatment in burned rats
      attenuated myocardial caspase expression, prevented burn-related myocardial Na+
      loading, attenuated myocyte cytokine responses, and improved myocardial
      contraction and relaxation. The present data suggest that signaling through
      myocardial caspases plays a pivotal role in burn-related myocyte sodium
      dyshomeostasis and myocyte inflammation, perhaps contributing to burn-related
      contractile dysfunction.

PMID- 17431086
TI  - Limiting sarcolemmal Na+ entry during resuscitation from ventricular fibrillation
      prevents excess mitochondrial Ca2+ accumulation and attenuates myocardial injury.
AB  - BACKGROUND: intracellular Na+ accumulation during ischemia and reperfusion leads
      to cytosolic Ca2+ overload through reverse-mode operation of the sarcolemmal Na+ 
      Ca2+ exchanger. Cytosolic Ca2+ accumulation promotes mitochondrial Ca2+ (Ca2+ m)
      overload, leading to mitochondrial injury. We investigated whether limiting
      sarcolemmal Na+ entry during resuscitation from ventricular fibrillation (VF)
      attenuates Ca2+ m overload and lessens myocardial dysfunction in a rat model of
      VF and closed-chest resuscitation. METHODS: hearts were harvested from 10 groups
      of 6 rats each representing baseline, 15 min of untreated VF, 15 min of VF with
      chest compression given for the last 5 min (VF/CC), and 60 min postresuscitation
      (PR). VF/CC and PR included four groups each randomized to receive before
      starting chest compression the new NHE-1 inhibitor AVE4454B (1.0 mg/kg), the Na+
      channel blocker lidocaine (5.0 mg/kg), their combination, or vehicle control. The
      left ventricle was processed for intracellular Na+ and Ca2+ m measurements.
      RESULTS: limiting sarcolemmal Na+ entry attenuated cytosolic Na+ increase during
      VF/CC and the PR phase and prevented Ca2+ m overload yielding levels that
      corresponded to 77% and 71% of control hearts at VF/CC and PR, without
      differences among specific Na+ -limiting interventions. Limiting sarcolemmal Na+
      entry attenuated reductions in left ventricular compliance during VF and prompted
      higher mean aortic pressure (110 +/- 7 vs. 95 +/- 11 mmHg, P < 0.001) and higher
      cardiac work index (159 +/- 34 vs. 126 +/- 29 g x m x min(-1) x kg(-1), P < 0.05)
      with lesser increases in circulating cardiac troponin I at 60 min PR.
      CONCLUSIONS: Na+ -limiting interventions prevented excess Ca2+ m accumulation
      induced by ischemia and reperfusion and ameliorated myocardial injury and
      dysfunction.

PMID- 17431088
TI  - A gripping reality: oxidative stress, inflammation, and the pathway to frailty.

PMID- 17431087
TI  - Bradykinin- and substance P-induced edema formation in the hamster cheek pouch is
      tyrosine kinase dependent.
AB  - The purpose of this study was to determine whether protein tyrosine kinase, a
      ubiquitous family of intracellular signaling enzymes that regulates endothelial
      cell function, modulates bradykinin- and substance P-induced increase in
      macromolecular efflux from the intact hamster cheek pouch microcirculation. Using
      intravital microscopy, I found that suffusion of bradykinin or substance P (each,
      0.5 and 1.0 microM) onto the cheek pouch elicited significant, concentration
      dependent leaky site formation and increase in clearance of fluorescein
      isothiocyanate-dextran (FITC-dextran; molecular mass, 70 kDa; P < 0.05). These
      responses were significantly attenuated by suffusion of genistein (1.0 microM) or
      tyrphostin 25 (10 microM), two structurally unrelated, nonspecific protein
      tyrosine kinase inhibitors (P < 0.05). Conceivably, the kinase(s) involved in
      this process could be agonist specific because genistein was more effective than
      tyrphostin 25 in attenuating bradykinin-induced responses while the opposite was
      observed with substance P. Both inhibitors had no significant effects on
      adenosine (0.5 M)-induced responses (P > 0.5). Collectively, these data suggest
      that the protein tyrosine kinase metabolic pathway modulates, in part, the
      edemagenic effects of bradykinin and substance P in the intact hamster cheek
      pouch microcirculation in a specific fashion.

PMID- 17431089
TI  - Point:Counterpoint: lung impedance measurements are/are not more useful than
      simpler measurements of lung function in animal models of pulmonary disease.

PMID- 17431090
TI  - Do the mitochondria of obese individuals respond to exercise training?

PMID- 17431091
TI  - Consequences of postural changes and removal of vestibular inputs on the movement
      of air in and out of the lungs of conscious felines.
AB  - A variety of experimental approaches in human subjects and animal models
      established that the vestibular system contributes to regulation of respiration.
      In cats, the surgical elimination of labyrinthine signals produced changes in the
      spontaneous activity and posturally related responses of a number of respiratory
      muscles. However, these effects were complex and sometimes varied between muscle
      compartments, such that the physiological role of vestibulo-respiratory responses
      is unclear. The present study determined the functional significance of vestibulo
      respiratory influences by examining the consequences of a bilateral
      labyrinthectomy on breathing rate and the pressure, volume, and flow rate of air
      exchanged during inspiration and expiration as body orientation with respect to
      gravity was altered. Data were collected from conscious adult cats acclimated to
      breathing through a facemask connected to a pneuomotach during 60 degrees head-up
      pitch and ear-down roll body rotations. Removal of vestibular inputs resulted in
      a 15% reduction in breathing rate, a 13% decrease in minute ventilation, a 16%
      decrease in maximal inspiratory airflow rate, and a 14% decrease in the maximal
      expiratory airflow rate measured when the animals were in the prone position.
      However, the lesions did not appreciably affect phasic changes in airflow
      parameters related to alterations in posture. These results suggest that the role
      of the vestibular system in the control of breathing is to modify baseline
      respiratory parameters in proportion to the general intensity of ongoing
      movements, and not to rapidly alter ventilation in accordance with body position.

PMID- 17431092
TI  - Class III antiarrhythmic methanesulfonanilides inhibit leukocyte recruitment in
      zebrafish.
AB  - Understanding fundamental molecular mechanisms that govern the transmigration and
      interstitial migration of leukocytes to sites of tissue damage and infection is
      of potential significance in identifying novel therapeutic targets for the
      management of chronic inflammatory disorders. CD31 is a mammalian cell adhesion
      molecule that regulates the recruitment of leukocytes from the circulation. Our
      recent unpublished work has suggested that homophilic ligation of CD31 can
      negatively regulate the ether-a-go-go-related gene (ERG) current within
      leukocytes to regulate cell-cell adhesion. To validate and probe the functional
      significance of ERG in leukocytes, we developed an infected wound model of
      inflammation in zebrafish and assessed the efficacy of two ERG-specific
      inhibitors, dofetilide and E4031, as well as an ERG-specific antisense RNA
      morpholino on neutrophil recruitment. Our data confirm a hitherto undescribed
      role for ERG in leukocytes, where inhibition or translational knockdown of ERG
      resulted in significant attenuation of the inflammatory response to an infectious
      stimulus. Inhibition of ERG was verified independently by a decrease in the
      ventricular heart rate, where ERG also functions in the repolarization of the
      cardiac action potential. Our results suggest that ERG-specific Class III
      antiarrhythmic drugs can modulate inflammatory responses to infection.

PMID- 17431093
TI  - Understanding phospholipase D (PLD) using leukocytes: PLD involvement in cell
      adhesion and chemotaxis.
AB  - Phospholipase D (PLD) is an enzyme that catalyzes the conversion of membrane
      phosphatidylcholine to choline and phosphatidic acid (PA; a second messenger).
      PLD is expressed in nearly all types of leukocytes and has been associated with
      phagocytosis, degranulation, microbial killing, and leukocyte maturation. With
      the application of recently developed molecular tools (i.e., expression vectors,
      silencing RNA, and specific antibodies), the demonstration of a key role for PLD
      in those and related cellular actions has contributed to a better awareness of
      its importance. A case in point is the recent findings that RNA interference
      mediated depletion of PLD results in impaired leukocyte adhesion and chemotaxis
      toward a gradient of chemokines, implying that PLD is necessary for leukocyte
      movement. We forecast that based on results such as those, leukocytes may prove
      to be useful tools to unravel still-unresolved mechanistic issues in the complex
      biology of PLD. Three such issues are considered here: first, whether the
      cellular actions of PLD are mediated entirely by PA (the product of its enzymatic
      reaction) or whether PLD by itself interacts with other protein signaling
      molecules; second, the current difficulty of defining a "PA consensus site" in
      the various intracellular protein targets of PA; and third, the resolution of
      specific PLD location (upstream or downstream) in a particular effector signaling
      cascade. There are reasons to expect that leukocytes and their leukemic cell line
      counterparts will continue yielding invaluable information to cell biologists to
      resolve standing molecular and functional issues concerning PLD.

PMID- 17431094
TI  - HIV-1 Nef impairs the dynamic of DC/NK crosstalk: different outcome of CD56(dim)
      and CD56(bright) NK cell subsets.
AB  - Dendritic cells (DCs) and natural killer (NK) cells are essential components of
      the innate immunity and play a critical role in the first phase of host defense
      against infection. Interactions between DCs and NK cells have been demonstrated
      in a variety of settings, with evidence emerging of complex bidirectional
      crosstalk between the two cell types. The accessory HIV-1 Nef protein is a
      crucial determinant for viral replication and pathogenesis. We previously
      demonstrated that Nef, hijacking DC functional activity, subverts the DC arm of
      immune response to escape the adaptive immune attack. Here, we monitor the effect
      of Nef on the outcome of the innate immune response, focusing on the impact of
      Nef on DC/NK crosstalk. We demonstrate that Nef up-regulates the ability of DCs
      to stimulate the immunoregulatory NK cells (CD56(bright)) as assessed by the
      activated phenotype, up-regulation of their proliferative response and INF-gamma
      release. On the other hand, Nef-pulsed DCs inhibit cytotoxic NK cells
      (CD56(dim)), as assessed by the reduced HLA-DR surface expression, reduced
      proliferation and cytotoxic activity. Moreover, in the presence of Nef-pulsed
      DCs, we found a significant up-regulation of TNF-alpha secretion and a
      significant reduction of IL-10, GM-CSF, MIP-1alpha and RANTES secretion. Our
      findings suggest that the Nef-induced dysregulation in the DC/NK cell crosstalk
      may represent a potential mechanism through which HIV escapes innate immune
      surveillance.

PMID- 17431095
TI  - Cannabinoids ameliorate cerebral dysfunction following liver failure via AMP
      activated protein kinase.
AB  - Hepatic encephalopathy (HE) is a neuropsychiatric disorder of complex
      pathogenesis caused by acute or chronic liver failure. We studied the etiology of
      cerebral dysfunction in a murine model of HE induced by either bile duct ligation
      or thioacetamide administration. We report that stimulation of cerebral AMP
      activated protein kinase (AMPK), a major intracellular energy sensor, is a
      compensatory response to liver failure. This function of AMPK is regulated by
      endocannabinoids. The cannabinoid system controls systemic energy balance via the
      cannabinoid receptors CB-1 and CB-2. Under normal circumstances, AMPK activity is
      mediated by CB-1 while CB-2 is barely detected. However, CB-2 is strongly
      stimulated in response to liver failure. Administration of delta9
      tetrahydrocannabinol (THC) augmented AMPK activity and restored brain function in
      WT mice but not in their CB-2 KO littermates. These results suggest that HE is a
      disease of energy flux. CB-2 signaling is a cerebral stress response mechanism
      and makes AMPK a promising target for its treatment by modulating the cannabinoid
      system.

PMID- 17431096
TI  - Beyond IkappaBs: alternative regulation of NF-kappaB activity.
AB  - The transcription factor nuclear factor-kappa B (NF-kappaB) is a crucial
      regulator of many physiological and patho-physiological processes, including
      control of the adaptive and innate immune responses, inflammation, proliferation,
      tumorigenesis, and apoptosis. Thus, the tight regulation of NF-kappaB activity
      within a cell is extremely important. The central mechanism of NF-kappaB
      regulation is the signal-induced proteolytic degradation of a family of
      cytoplasmic inhibitors of NF-kappaB, the IkappaBs. However, with the discovery of
      an IkappaB-independent noncanonical or "alternative" pathway of NF-kappaB
      activation, the importance of other regulatory mechanisms responsible for the
      fine-tuning of NF-kappaB became clear. Post-translational modification,
      especially phosphorylation, of the Rel proteins, of which dimeric NF-kappaB is
      composed, are such alternative regulatory mechanisms. The best analyzed example
      is RelA phosphorylation, which takes place at specific amino acids resulting in
      distinct functional changes of this gene regulatory protein. The interaction of
      NF-kappaB with other proteins such as glucocorticoid receptors is very important
      for the regulation of NF-kappaB activity. Recently, exciting new concepts of
      IkappaB-independent NF-kappaB control like dimer exchange and nucleolar
      sequestration of RelA have been described, indicating that many aspects of NF
      kappaB control are waiting to be discovered.

PMID- 17431097
TI  - Activation of the alpha7 nAChR reduces acid-induced acute lung injury in mice and
      rats.
AB  - New evidence indicates that neural mechanisms can down-regulate acute
      inflammation. In these studies, we tested the potential role of the alpha7
      nicotinic acetylcholine receptor (alpha7 nAChR) in a rodent model of acid-induced
      acute lung injury. We first determined that the alpha7 nAChR was expressed by
      alveolar macrophages and lung epithelial cells. Then, using an acid-induced acute
      lung injury mouse model, we found that nicotine, choline, and PNU-282,987 (a
      specific alpha7 nAChR agonist) decreased excess lung water and lung vascular
      permeability, and reduced protein concentration in the bronchoalveolar lavage
      (BAL). Deficiency of alpha7 nAChR resulted in a 2-fold increase in excess lung
      water and lung vascular permeability. The reduction of proinflammatory cytokines
      (macrophage inflammatory protein-2 and TNF-alpha) in the BAL with nicotine
      probably resulted from the suppression of NF-kappaB activation in alveolar
      macrophages. The beneficial effect of nicotine was also tested in rat model of
      acid-induced acute lung injury in which BAL protein and receptor for advanced
      glycation end products (RAGE), a marker of type I cell injury, were reduced by
      nicotine treatment. These results indicate that activation of alpha7 nAChR may
      provide a new therapeutic pathway for the treatment of acute lung injury.

PMID- 17431098
TI  - Modulation of human airway smooth muscle migration by lipid mediators and Th-2
      cytokines.
AB  - Cysteinyl leukotrienes and the T helper (Th)-2 cytokines IL-5 and IL-13 directly
      modulate human airway smooth muscle functions such as contraction and
      proliferation. We studied the effects of other lipid mediators involved in asthma
      pathophysiology such as prostaglandin D(2) (PGD(2)), lipoxin, and isoprostanes,
      and the cytokines, IL-5, IL-4, and IL-13 on human airway smooth muscle cell
      migration. Chemotaxis and chemokinesis of cultured airway smooth muscle cells
      from humans without asthma (second to fifth passages, n = 6) were studied using
      collagen-I-coated polycarbonate membranes in Transwell culture plates. Receptor
      expression and kinase activation were studied by flow cytometry, polymerase chain
      reaction, and Western blotting techniques. In contrast to LTE(4)- stimulated (10(
      6) M) chemokinesis and LTE(4)-primed migration toward platelet-derived growth
      factor (PDGF), isoprostane 15-F(2t)-IsoP, and IL-5 were neither chemotactic nor
      chemokinetic. PGD(2) (10(-10)-10(-6) M) was a chemoattractant and primed
      migration toward PDGF through the DP(2)/CRTh(2) receptor. Although airway smooth
      muscle cells did not express the lipoxin A(4) cognate receptor, LTE(4)-primed
      migration toward PDGF was blocked by lipoxin A(4) (10(-6) M), suggesting that
      this is mediated through CysLT(1)R antagonism. IL-13 (10 ng/ml), but not IL-4
      (0.1-100 ng/ml), augmented migration toward PDGF. This was associated with
      increased Src-kinase phosphorylation and up-regulation of PDGF-alpha and -beta
      receptors, and was attenuated by IL-13Ralpha- and IL-4Ralpha-neutralizing
      antibodies, an Src-kinase antagonist (PP1, 3 muM), a CysLT(1)R antagonist,
      montelukast (10(-6) M), and by lipoxin A(4) (10(-6) M). PGD(2) and IL-13 promote
      human airway smooth muscle migration. IL-13 can promote airway smooth muscle
      migration through Src-kinase and leukotriene-dependent pathways. This may
      contribute to the accumulation of smooth muscle cells in remodeled airway
      submucosa.

PMID- 17431099
TI  - Erratum: figure.

PMID- 17431100
TI  - Uncommon tumors and exceptional therapies: paradox or paradigm?
AB  - Why does it seem that, repeatedly, when a new treatment with a striking effect is
      discovered in the cancer field, it is effective for a very rare cancer type? For
      example, groundbreaking therapeutic discoveries have been made for extremely
      uncommon malignancies such as hairy cell leukemia, chronic myelogenous leukemia,
      seminoma, gastrointestinal stromal tumor, (del)5q myelodysplastic syndrome, and
      acute promyelocytic leukemia. In contrast, progress in the most common and most
      intensively studied tumors - lung, breast, prostate, and colon cancer - has been
      slow and incremental. We hypothesize that the reason for this phenomenon is that
      the pathophysiologic basis for a tumor being rare is one and the same as the
      reason that it may ultimately be so treatable. That is, if a cancer can be
      derived only via a single aberrant molecular genetic aberration, then it should
      be both rare and easily targeted by a molecular cancer therapeutic approach. If,
      on the other hand, many distinct pathways can lead to the development of a
      specific tumor type, it should occur much more commonly and be significantly more
      difficult to treat. The corollary to our hypothesis is the prediction that new
      therapies will continue to show their most salutary effects in rare cancers.
      Furthermore, only by stratifying the common tumors, especially when using
      targeted agents, into the molecular subsets of diseases that compose them are we
      likely to achieve a substantial effect in these disorders.

PMID- 17431101
TI  - The randomized discontinuation trial: a phase II design to assess growth
      inhibitory agents.
AB  - An increasing number of putative anticancer targets and drugs have been
      identified with many of these expected to be growth inhibitory. Clinical
      development of these agents in the phase II setting is challenging because tumor
      shrinkages, or at least tumor shrinkages that meet the standard definitions of
      objective response, are not expected. Time to progression end points are however
      problematic because expected times in the absence of therapy (the null
      hypothesis) cannot be predicted accurately, thus requiring trials to enroll a
      concurrent control group. Another problem is that the patient population that
      will benefit from a new drug remains poorly defined in early-phase development.
      The randomized discontinuation trial design addresses both of these issues. All
      patients are initially treated with the drug; patients with an objective response
      continue therapy; patients who do not progress or experience excess toxicity
      within a prespecified "run-in" period are then randomized to continuing or
      discontinuing therapy in a double-blind, placebo controlled manner. Despite
      certain limitations that need to be recognized, the ability of this design to
      "select" a cohort most likely to benefit and to rigorously evaluate the disease
      stabilizing activity of an investigational agent provides multiple advantages.

PMID- 17431102
TI  - Inhibition of the heat shock protein 90 molecular chaperone in vitro and in vivo
      by novel, synthetic, potent resorcinylic pyrazole/isoxazole amide analogues.
AB  - Although the heat shock protein 90 (HSP90) inhibitor 17-allylamino-17
      demethoxygeldanamycin (17-AAG) shows clinical promise, potential limitations
      encourage development of alternative chemotypes. We discovered the 3,4
      diarylpyrazole resorcinol CCT018159 by high-throughput screening and used
      structure-based design to generate more potent pyrazole amide analogues,
      exemplified by VER-49009. Here, we describe the detailed biological properties of
      VER-49009 and the corresponding isoxazole VER-50589. X-ray crystallography showed
      a virtually identical HSP90 binding mode. However, the dissociation constant
      (K(d)) of VER-50589 was 4.5 +/- 2.2 nmol/L compared with 78.0 +/- 10.4 nmol/L for
      VER-49009, attributable to higher enthalpy for VER-50589 binding. A competitive
      binding assay gave a lower IC(50) of 21 +/- 4 nmol/L for VER-50589 compared with
      47 +/- 9 nmol/L for VER-49009. Cellular uptake of VER-50589 was 4-fold greater
      than for VER-49009. Mean cellular antiproliferative GI(50) values for VER-50589
      and VER-49009 for a human cancer cell line panel were 78 +/- 15 and 685 +/- 119
      nmol/L, respectively, showing a 9-fold potency gain for the isoxazole. Unlike 17
      AAG, but as with CCT018159, cellular potency of these analogues was independent
      of NAD(P)H:quinone oxidoreductase 1/DT-diaphorase and P-glycoprotein expression.
      Consistent with HSP90 inhibition, VER-50589 and VER-49009 caused induction of
      HSP72 and HSP27 alongside depletion of client proteins, including C-RAF, B-RAF,
      and survivin, and the protein arginine methyltransferase PRMT5. Both caused cell
      cycle arrest and apoptosis. Extent and duration of pharmacodynamic changes in an
      orthotopic human ovarian carcinoma model confirmed the superiority of VER-50589
      over VER-49009. VER-50589 accumulated in HCT116 human colon cancer xenografts at
      levels above the cellular GI(50) for 24 h, resulting in 30% growth inhibition.
      The results indicate the therapeutic potential of the resorcinylic
      pyrazole/isoxazole amide analogues as HSP90 inhibitors.

PMID- 17431103
TI  - Use of fluorescent labeled anti-epidermal growth factor receptor antibody to
      image head and neck squamous cell carcinoma xenografts.
AB  - Physicians and surgeons rely on subtle tissue changes to detect the extent of
      tumors and the presence of residual disease in the clinical setting. The
      development of a cancer-specific fluorescent contrast agent has the potential to
      provide real-time tumor imaging in the clinic or operating room. Because
      epidermal growth factor receptor (EGFR) is highly overexpressed on the surface of
      head and neck squamous cell carcinoma (HNSCC), we sought to determine if
      fluorescently labeled anti-EGFR antibody could be used to image HNSCC xenografts
      in vivo. Cetuximab or control isotype-matched IgG1 was conjugated with the Cy5.5
      fluorochrome and systemically injected into mice bearing human split thickness
      skin grafts, tumor cell line xenografts, transplanted human tumor xenografts, or
      mouse mesothelioma tumors. Xenografts were imaged by time-domain fluorescence
      imaging or fluorescence stereomicroscopy. Both imaging modalities detected
      specific uptake of cetuximab-Cy5.5 in HNSCC xenografts with significantly higher
      fluorescence levels relative to control IgG1-Cy5.5. Tumor xenograft fluorescence
      was higher compared with background (before injection), human split thickness
      skin grafts, or mouse mesothelioma tumors at 24, 48, and 72 h. Fluorescence was
      detected in multiple HNSCC tumor cell lines with variable EGFR expression levels.
      Mock resections of flank tumors using fluorescence stereomicroscopy showed that
      small (2 mm) specimens could be detected in the surgical wound bed. These results
      show the feasibility of using fluorescently labeled anti-EGFR antibody to detect
      human tumors in the surgical setting.

PMID- 17431104
TI  - Calcium-activated endoplasmic reticulum stress as a major component of tumor cell
      death induced by 2,5-dimethyl-celecoxib, a non-coxib analogue of celecoxib.
AB  - A drawback of extensive coxib use for antitumor purposes is the risk of life
      threatening side effects that are thought to be a class effect and probably due
      to the resulting imbalance of eicosanoid levels. 2,5-Dimethyl-celecoxib (DMC) is
      a close structural analogue of the selective cyclooxygenase-2 inhibitor celecoxib
      that lacks cyclooxygenase-2-inhibitory function but that nonetheless is able to
      potently mimic the antitumor effects of celecoxib in vitro and in vivo. To
      further establish the potential usefulness of DMC as an anticancer agent, we
      compared DMC and various coxibs and nonsteroidal anti-inflammatory drugs with
      regard to their ability to stimulate the endoplasmic reticulum (ER) stress
      response (ESR) and subsequent apoptotic cell death. We show that DMC increases
      intracellular free calcium levels and potently triggers the ESR in various tumor
      cell lines, as indicated by transient inhibition of protein synthesis, activation
      of ER stress-associated proteins GRP78/BiP, CHOP/GADD153, and caspase-4, and
      subsequent tumor cell death. Small interfering RNA-mediated knockdown of the
      protective chaperone GRP78 further sensitizes tumor cells to killing by DMC,
      whereas inhibition of caspase-4 prevents drug-induced apoptosis. In comparison,
      celecoxib less potently replicates these effects of DMC, whereas none of the
      other tested coxibs (rofecoxib and valdecoxib) or traditional nonsteroidal anti
      inflammatory drugs (flurbiprofen, indomethacin, and sulindac) trigger the ESR or
      cause apoptosis at comparable concentrations. The effects of DMC are not
      restricted to in vitro conditions, as this drug also generates ER stress in
      xenografted tumor cells in vivo, concomitant with increased apoptosis and reduced
      tumor growth. We propose that it might be worthwhile to further evaluate the
      potential of DMC as a non-coxib alternative to celecoxib for anticancer purposes.

PMID- 17431105
TI  - Liposomal curcumin with and without oxaliplatin: effects on cell growth,
      apoptosis, and angiogenesis in colorectal cancer.
AB  - The role of curcumin (diferuloylmethane), a proapoptotic compound, for the
      treatment of cancer has been an area of growing interest. Curcumin in its free
      form is poorly absorbed in the gastrointestinal tract and therefore may be
      limited in its clinical efficacy. Liposome encapsulation of this compound would
      allow systemic administration. The current study evaluated the preclinical
      antitumor activity of liposomal curcumin in colorectal cancer. We also compared
      the efficacy of liposomal curcumin with oxaliplatin, a standard chemotherapy for
      this malignancy. In vitro treatment with liposomal curcumin induced a dose
      dependent growth inhibition [3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt] and apoptosis
      [poly(ADP-ribose) polymerase] in the two human colorectal cancer cell lines
      tested (LoVo and Colo205 cells). There was also synergism between liposomal
      curcumin and oxaliplatin at a ratio of 4:1 in LoVo cells in vitro. In vivo,
      significant tumor growth inhibition was observed in Colo205 and LoVo xenografts,
      and the growth inhibition by liposomal curcumin was greater than that for
      oxaliplatin (P < 0.05) in Colo205 cells. Tumors from animals treated with
      liposomal curcumin showed an antiangiogenic effect, including attenuation of CD31
      (an endothelial marker), vascular endothelial growth factor, and interleukin-8
      expression by immunohistochemistry. This study establishes the comparable or
      greater growth-inhibitory and apoptotic effects of liposomal curcumin with
      oxaliplatin both in vitro and in vivo in colorectal cancer. We are currently
      developing liposomal curcumin for introduction into the clinical setting.

PMID- 17431106
TI  - Molecular mechanisms of the chemopreventive effect on hepatocellular carcinoma
      development in Mdr2 knockout mice.
AB  - Dietary antioxidants and selenium compounds were shown to have a therapeutic
      effect against hepatocellular carcinoma in several mouse models. We tested the
      effects of tannic acid and selenomethionine on hepatocellular carcinoma
      development in Mdr2 knockout (Mdr2-KO) mice. Mdr2-KO and age-matched Mdr2
      heterozygous control mice were fed with tannic acid or selenomethionine during
      the first 3 months of life. Then, several mice from each group were sacrificed,
      and liver tissue samples were removed for analysis. The remaining mice were fed a
      regular diet until the age of 16 months, at which time the number and size of
      liver tumors were determined. Liver tissue samples of 3-month-old mice were
      subjected to gene expression profiling analysis using cDNA macroarrays containing
      probes for 240 genes that regulate responses to oxidative stress and inflammation
      or lipid metabolism. Both tannic acid and selenomethionine had partial
      chemopreventive effect on development of hepatocellular carcinoma in Mdr2-KO
      mice: they reduced the incidence of large tumor nodules (diameter >1 cm) at age
      16 months. Both agents inhibited gene expression and reversed up-regulation of
      many genes that control inflammation or response to oxidative stress in Mdr2-KO
      livers at age 3 months. This inhibitory effect on gene expression correlated with
      the ability of agents to reduce incidence of large tumors: selenomethionine was
      more active than tannic acid in both aspects. Understanding the molecular
      mechanism of chemoprevention effect could improve our therapeutic modalities
      while using these agents.

PMID- 17431107
TI  - Loss of mitochondrial membrane potential is inhibited by bombesin in etoposide
      induced apoptosis in PC-3 prostate carcinoma cells.
AB  - Neuroendocrine secretory products and their interactions with epithelial prostate
      cells are currently under investigation in order to understand their significance
      in the pathogenesis, prognosis, and therapy of prostate carcinoma. These
      neuropeptides have the potential to disrupt the balance between cell death and
      cell growth in the tumor. Our research was based on the role of bombesin in
      modulating the mitochondrial membrane potential (Delta psi(m)) in cell death
      induced by etoposide on PC-3 cells. Cells were cultured and stained with
      5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC
      1). At low membrane potentials, JC-1 produces a green fluorescence, and at high
      membrane potentials, it forms "J aggregates" with red fluorescence. Cells were
      examined in a confocal microscope. For quantitative analyses, regions of interest
      were selected. The size, number of pixels, and ratios between fluorescence
      intensity in the red and green channels in each region of interest were
      calculated. The loss of Delta psi(m) in etoposide-treated PC-3 cells was
      prevented by bombesin. The quantitative analysis of JC-1-stained cells revealed a
      significant decrease in the red (high Delta psi(m)) to green (low Delta psi(m))
      ratio in etoposide-treated cells when compared with control cells, which was
      restored in the presence of bombesin (P < 0.00001). The interaction between
      treatments and area (P = 0.0002) was highly significant, and confirms that PC-3
      cells keep their apoptosis machinery, showing an apoptotic volume decrease in
      response to etoposide. The protection by bombesin occurs by inhibition of
      apoptosis and maintenance of mitochondrial integrity. New therapeutic protocols
      and trials need to be developed to test drugs acting through the neutralization
      of antiapoptotic intracellular pathways mediated by neuroendocrine hormones.

PMID- 17431108
TI  - The RET oncogene is a critical component of transcriptional programs associated
      with retinoic acid-induced differentiation in neuroblastoma.
AB  - Differentiation is a key feature in pathologic classification and prognosis of
      neuroblastic tumors, although the underlying molecular mechanisms are not well
      defined. To identify key differentiation-related molecules and pathways, we
      evaluated gene expression during retinoic acid (RA)-induced differentiation of
      seven neuroblastic tumor cell lines. Transcriptional response to RA was highly
      variable among cell lines despite the fact that six of seven showed similar
      morphologic changes. RA consistently altered expression of a small set of genes,
      some of which are known to play a role in neurogenesis and differentiation.
      Expression of genes that were regulated by RA was associated with important
      clinical subgroups of neuroblastic tumors and were differentially expressed by
      stroma-rich and stroma-poor subtypes. RET, a receptor tyrosine kinase involved
      with differentiation, was consistently up-regulated throughout the time course of
      RA treatment in the majority of neuroblastic tumor cell lines. Interference with
      RET activation abrogated RA-induced transcriptional programs and differentiation,
      suggesting a key role of RET in this process. The core set of RA-regulated genes
      includes critical molecular components of pathways necessary for neuroblastic
      tumor differentiation and have potential as therapeutic targets and molecular
      markers of response to differentiating agents.

PMID- 17431109
TI  - Levels of p27(kip1) determine Aplidin sensitivity.
AB  - Aplidin (plitidepsin) is a novel anticancer drug isolated from the marine
      tunicate Aplidium albicans. Aplidin shows potent antitumor activity in
      preclinical models against a wide variety of human tumors. Aplidin is currently
      in phase II clinical trials in a variety of solid tumors and hematologic
      malignancies. Moreover, clinical studies of Aplidin in combination with other
      agents are ongoing because it generally lacks cross-resistance with other known
      cytotoxic drugs. The mode of action of Aplidin in tumor cells is only partially
      understood. Aplidin induces an early oxidative stress response, which results in
      a rapid and sustained activation of the epidermal growth factor receptor, the
      nonreceptor protein tyrosine kinase Src, and the serine threonine kinases c-Jun
      NH(2)-terminal kinase and p38 mitogen-activated protein kinase. Here, we show
      that sensitivity to Aplidin correlates inversely with the levels of expression of
      the cyclin-dependent kinase inhibitor p27(kip1) (p27) in a panel of low passaged
      human sarcoma cell lines. Aplidin induces p27 through an oxidation-dependent
      mechanism and the reduction of p27 levels by specific short hairpin RNA increases
      Aplidin sensitivity. We confirmed these results in p27 null mouse embryonic
      fibroblasts corroborating the specificity of the p27 role in Aplidin response
      because p21(waf1) null mouse embryonic fibroblasts do not show this increased
      sensitivity. We propose a mechanism of action of Aplidin involving p27 and
      support the analysis of p27 in the response to Aplidin in currently ongoing
      clinical trials to establish the levels of this protein as response predictor.

PMID- 17431110
TI  - Farnesyl transferase inhibitors impair chromosomal maintenance in cell lines and
      human tumors by compromising CENP-E and CENP-F function.
AB  - Farnesyl transferase inhibitors (FTI) exhibit anticancer activity as a single
      agent in preclinical studies and show promise in combination with other
      therapeutics in clinical trials. Previous studies show that FTIs arrest cancer
      cells in mitosis; however, the mechanism by which this occurs is unclear. Here,
      we observed that treatment of various cancer cell lines with the FTI lonafarnib
      caused mitotic chromosomal alignment defects, leaving cells in a pseudometaphase
      state, whereby both aligned chromosomes and chromosomes juxtaposed to the spindle
      poles (termed "lagging chromosomes") were observed in the same cell. To determine
      how this occurs, we investigated the functionality of two farnesylated mitotic
      proteins, CENP-E and CENP-F, which mediate chromosomal capture and alignment. The
      data show that lonafarnib in proliferating cancer cells depletes CENP-E and CENP
      F from metaphase but not prometaphase kinetochores. Loss of CENP-E and CENP-F
      metaphase localization triggered aberrant chromosomal maintenance, causing
      aligned chromosomes to be prematurely released from the spindle equator and
      become lagging chromosomes, resulting in a mitotic delay. Furthermore, lonafarnib
      treatment reduces sister kinetochore tension and activates the BubR1 spindle
      checkpoint, suggesting that farnesylation of CENP-E and CENP-F is critical for
      their functionality in maintaining kinetochore-microtubule interactions.
      Importantly, apparently similar chromosomal alignment defects were observed in
      head and neck tumors samples from a phase I trial with lonafarnib, providing
      support that lonafarnib disrupts chromosomal maintenance in human cancers.
      Lastly, to examine how farnesylation could regulate CENP-E in mediating
      kinetochore-microtubule attachments, we examined possible docking motifs of a
      farnesyl group on the outer surface of the microtubule. This analysis revealed
      three hydrophobic patches on the tubulin dimer for insertion of a farnesyl group,
      alluding to the possibility of an association between a farnesyl group and the
      microtubule.

PMID- 17431111
TI  - Tumor cytotoxicity and endothelial Rac inhibition induced by TNP-470 in
      anaplastic thyroid cancer.
AB  - Anaplastic thyroid carcinoma is an aggressive form of cancer with no treatment.
      Angiogenesis inhibitors, such as TNP-470, a synthetic derivative of fumagillin,
      have been shown to reduce tumor size and increase survival in heterotopic animal
      models of thyroid cancer. Our goals were to determine the effect of TNP-470 on
      anaplastic thyroid cancer using an orthotopic murine model, to identify the
      molecular pathways of TNP-470 actions on endothelial cells, and to determine the
      non-endothelial tumor effects of TNP-470. We injected human anaplastic thyroid
      carcinoma cells (DRO'90) into the thyroid glands of nude mice. Mice received TNP
      470 (30 mg/kg) s.c. for 6 weeks. TNP-470 prolonged survival and reduced liver
      metastases. TNP-470 had direct cytotoxic effects on anaplastic thyroid carcinoma
      cells in vitro and in vivo. Paradoxically, TNP-470 increased vascular endothelial
      growth factor secretion from tumor cells in vitro and in vivo. However, there was
      no associated increase in tumor microvessel density. In endothelial cells, TNP
      470 prevented vascular endothelial growth factor-induced endothelial
      permeability, intercellular gap formation, and ruffle formation by preventing
      Rac1 activation.

PMID- 17431112
TI  - Luteolin sensitizes the anticancer effect of cisplatin via c-Jun NH2-terminal
      kinase-mediated p53 phosphorylation and stabilization.
AB  - Luteolin is an important flavonoid with a potential anticancer effect. In this
      study, we examined the molecular mechanisms involved in the sensitization effect
      of luteolin on cancer cell killing induced by cisplatin, an important cancer
      chemotherapeutic agent. First, we provided evidence that the sensitization effect
      of luteolin on cisplatin-induced apoptosis is p53 dependent, as such effect is
      only found in p53 wild-type cancer cells but not in p53 mutant cancer cells.
      Moreover, knockdown of p53 by small interfering RNA made p53 wild-type cancer
      cells resistant to luteolin and cisplatin. Second, we observed a significant
      increase of p53 protein level in luteolin-treated cancer cells without increase
      of p53 mRNA level, indicating the possible effect of luteolin on p53
      posttranscriptional regulation. Third, we identified the critical role of c-Jun
      NH(2)-terminal kinase (JNK) in regulation of p53 protein stability: luteolin
      activates JNK, and JNK then stabilizes p53 via phosphorylation, leading to
      reduced ubiquitination and proteasomal degradation. Finally, by using an in vivo
      nude mice xenograft model, we confirmed that luteolin enhanced the cancer
      therapeutic activity of cisplatin via p53 stabilization and accumulation. In
      summary, data from this study reveal a novel molecular mechanism involved in the
      anticancer effect of luteolin and support its potential clinical application as a
      chemosensitizer in cancer therapy.

PMID- 17431113
TI  - Identification of a novel inhibitor of urokinase-type plasminogen activator.
AB  - Urokinase-type plasminogen activator (uPA), a highly restricted serine protease,
      plays an important role in the regulation of diverse physiologic and pathologic
      processes. Strong clinical and experimental evidence has shown that elevated uPA
      expression is associated with cancer progression, metastasis, and shortened
      survival in patients. uPA has been considered as a promising molecular target for
      development of anticancer drugs. Here, we report the identification of several
      new uPA inhibitors using a high-throughput screen from a chemical library. From
      these uPA inhibitors, molecular modeling and docking studies identified 4
      oxazolidinone as a novel lead pharmacophore. Optimization of the 4-oxazolidinone
      pharmacophore resulted in a series of structurally modified compounds with
      improved potency and selectivity. One of the 4-oxazolidinone analogues, UK122,
      showed the highest inhibition of uPA activity. The IC(50) of UK122 in a cell-free
      indirect uPA assay is 0.2 micromol/L. This compound also showed no or little
      inhibition of other serine proteases such as thrombin, trypsin, plasmin, and the
      tissue-type plasminogen activator, indicating its high specificity against uPA.
      Moreover, UK122 showed little cytotoxicity against CFPAC-1 cells (IC(50) >100
      micromol/L) but significantly inhibited the migration and invasion of this
      pancreatic cancer cell line. Our data show that UK122 could potentially be
      developed as a new anticancer agent that prevents the invasion and metastasis of
      pancreatic cancer.

PMID- 17431114
TI  - Inhibition of both focal adhesion kinase and insulin-like growth factor-I
      receptor kinase suppresses glioma proliferation in vitro and in vivo.
AB  - Multiple genetic aberrations in human gliomas contribute to their highly
      infiltrative and rapid growth characteristics. Focal adhesion kinase (FAK)
      regulates tumor migration and invasion. Insulin-like growth factor-I receptor
      (IGF-IR), whose expression correlates with tumor grade, is involved in
      proliferation and survival. We hypothesized that inhibiting the phosphorylation
      of FAK and IGF-IR by NVP-TAE226 (hereafter called TAE226), a novel dual tyrosine
      kinase inhibitor of FAK and IGF-IR, would suppress the growth and invasion of
      glioma cells. In culture, TAE226 inhibited extracellular matrix-induced
      autophosphorylation of FAK (Tyr(397)). TAE226 also inhibited IGF-I-induced
      phosphorylation of IGF-IR and activity of its downstream target genes such as
      MAPK and Akt. TAE226 retarded tumor cell growth as assessed by a cell viability
      assay and attenuated G(2)-M cell cycle progression associated with a decrease in
      cyclin B1 and phosphorylated cdc2 (Tyr(15)) protein expression. TAE226 treatment
      inhibited tumor cell invasion by at least 50% compared with the control in an in
      vitro Matrigel invasion assay. Interestingly, TAE226 treatment of tumor cells
      containing wild-type p53 mainly exhibited G(2)-M arrest, whereas tumor cells
      bearing mutant p53 underwent apoptosis. Induction of apoptosis by TAE226 was
      substantiated by detection of caspase-3/7 activation and poly(ADP-ribose)
      polymerase cleavage and by an Annexin V apoptosis assay. More importantly, TAE226
      treatment significantly increased the survival rate of animals in an intracranial
      glioma xenograft model. Collectively, these data show that blocking the signaling
      pathways of FAK and IGF-IR with TAE226 has the potential to be an efficacious
      treatment for human gliomas.

PMID- 17431115
TI  - S-phase checkpoints regulate Apo2 ligand/TRAIL and CPT-11-induced apoptosis of
      prostate cancer cells.
AB  - As S-phase checkpoints play critical roles in maintaining genomic integrity and
      replicating the human genome correctly, understanding the molecular mechanism by
      which they regulate the therapeutic response is of great interest. Previously, we
      reported that the cytotoxic effect of a zinc-bound form of Apo2 ligand/tumor
      necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL), which is
      currently evaluated in clinical trials, in combination with low-dose CPT-11,
      induces apoptosis of C4-2 human prostate cancer cells and tissues. Here, we show
      that apoptosis, induced synergistically by this combination treatment, was
      associated with accumulation of cells in early S phase, indicated by cell cycle
      analyses, increased proliferating cell nuclear antigen, and Chk2-Thr(68)
      phosphorylation in tumors xenografted in mice. The combination treatment induced
      an S-phase checkpoint response through activation of Chk2 and Chk1 by the ataxia
      telangiectasia mutated and ataxia telangiectasia mutated and Rad3 related
      kinases, leading to phosphorylation and decreased Cdc25A levels. Cdc25A-dependent
      regulation of cyclin-dependent kinase 2 (Cdk2) and changes in association of
      p21(WAF1/CIP1) and hSpy1 with Cdk2 resulted in inhibition of Cdk2-associated
      kinase activity. Knockdown of ataxia telangiectasia mutated/Chk2 and ataxia
      telangiectasia mutated and Rad3 related/Chk1 by small inhibitory RNAs abrogated
      the S-phase checkpoint and accelerated apoptosis, resulting in caspase-3
      activation and poly(ADP-ribose) polymerase 1 cleavage following combination
      treatment. Thus, Apo2L/TRAIL + CPT-11 treatment-induced apoptosis is regulated
      through an S-phase checkpoint controlled by the Chk2-Cdc25A and Chk1-Cdc25A
      pathways and inhibition of Cdk2-associated kinase activity. Low-dose CPT-11 and
      aphidicolin increased the proportion of S-phase cells and sensitized cells to
      Apo2L/TRAIL, by inducing phosphatidylserine externalization, caspase activation,
      and poly(ADP-ribose) polymerase 1 cleavage. Combinations with S-phase arrest
      inducing chemotherapeutic drugs may represent promising avenues for clinical
      development of Apo2L/TRAIL.

PMID- 17431116
TI  - Clofibric acid, a peroxisome proliferator-activated receptor alpha ligand,
      inhibits growth of human ovarian cancer.
AB  - Recent reports have shown that peroxisome proliferator-activated receptor
      (PPAR)alpha ligands reduce growth of some types of malignant tumors and prevent
      carcinogenesis. In this study, we investigated the inhibitory effect of clofibric
      acid (CA), a ligand for PPARalpha on growth of ovarian malignancy, in in vivo and
      in vitro experiments using OVCAR-3 and DISS cells derived from human ovarian
      cancer and aimed to elucidate the molecular mechanism of its antitumor effect. CA
      treatment significantly suppressed the growth of OVCAR-3 tumors xenotransplanted
      s.c. and significantly prolonged the survival of mice with malignant ascites
      derived from DISS cells as compared with control. CA also dose-dependently
      inhibited cell proliferation of cultured cell lines. CA treatment increased the
      expression of carbonyl reductase (CR), which promotes the conversion of
      prostaglandin E(2) (PGE(2)) to PGF(2alpha), in implanted OVCAR-3 tumors as well
      as cultured cells. CA treatment decreased PGE(2) level as well as vascular
      endothelial growth factor (VEGF) amount in both of OVCAR-3-tumor and DISS-derived
      ascites. Reduced microvessel density and induced apoptosis were found in solid
      OVCAR-3 tumors treated by CA. Transfection of CR expression vector into mouse
      ovarian cancer cells showed significant reduction of PGE(2) level as well as VEGF
      expression. These results indicate that CA produces potent antitumor effects
      against ovarian cancer in conjunction with a reduction of angiogenesis and
      induction of apoptosis. We conclude that CA could be an effective agent in
      ovarian cancer and should be tested alone and in combination with other
      anticancer drugs.

PMID- 17431117
TI  - Chemotherapeutic drugs sensitize cancer cells to TRAIL-mediated apoptosis: up
      regulation of DR5 and inhibition of Yin Yang 1.
AB  - Several chemotherapeutic drugs in combination with tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) result in reversal of resistance to TRAIL
      mediated apoptosis through up-regulation of DR5 expression. The promoter of DR5
      has one putative binding site for the transcription repressor Yin Yang 1 (YY1),
      and thus, we hypothesized that the sensitizing drugs may inhibit YY1. We have
      found that treatment of tumor cells with various chemotherapeutic drugs inhibited
      nuclear factor-kappaB. We examined whether drugs also inhibit YY1 activity and
      whether YY1 inhibition correlates with up-regulation of DR5 expression and
      sensitization of cells to TRAIL-induced apoptosis. The TRAIL- and drug-resistant
      prostate carcinoma PC-3 cell line was treated with CDDP, VP-16, ADR, and
      vincristine. DR5 luciferase reporter constructs and small interfering RNA against
      YY1 were used to determine the role of YY1 in DR5 transcription. Pretreatment of
      PC-3 cells and other tumor cell lines with various chemotherapeutic drugs
      sensitized the cells to TRAIL-induced apoptosis concurrently with up-regulation
      of DR5 expression and inhibition of YY1 expression and its DNA-binding activity.
      The baseline luciferase activity in PC-3 cells transfected with the wild-type DR5
      reporter was significantly augmented in cells transfected with DR5 constructs
      carrying deletions or mutation in the YY1-binding site. Treatment with drug
      enhanced DR5 wild-type luciferase activity, with no increase in cells transfected
      with the YY1-deleted or YY1-mutated constructs. Cells transfected with YY1 small
      interfering RNA showed up-regulation of DR5 expression and sensitization to TRAIL
      mediated apoptosis. The findings provide evidence that drug-induced sensitization
      of tumor cells to TRAIL is mediated, in part, by inhibition of the transcription
      repressor YY1 and up-regulation of DR5 expression. Hence, YY1 may be a potential
      therapeutic target to reverse resistance to TRAIL-induced apoptosis.

PMID- 17431118
TI  - Dasatinib (BMS-354825) inhibits Stat5 signaling associated with apoptosis in
      chronic myelogenous leukemia cells.
AB  - Dasatinib (BMS-354825) is a novel, oral, potent, multi-targeted kinase inhibitor
      of Bcr-Abl and Src family kinases (SFK) and is a promising cancer therapeutic
      agent. Preclinical data indicate that dasatinib is 325-fold more potent than
      imatinib against cells expressing wild-type Bcr-Abl, and that dasatinib is active
      against 18 of 19 Bcr-Abl mutations known to cause imatinib resistance. Phase I
      clinical data show that dasatinib is well tolerated and highly effective for the
      treatment of imatinib-resistant/imatinib-intolerant chronic myelogenous leukemia
      (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia. However,
      the molecular mechanism of action of dasatinib is not fully understood. In this
      study, we confirm that dasatinib inhibits tyrosine phosphorylation of SFKs,
      including Src, Hck, and Lyn, in K562 human CML cells. Significantly, downstream
      signal transducer and activator of transcription 5 (Stat5) signaling is also
      blocked by dasatinib as shown by decreases in levels of phosphorylated Stat5 and
      Stat5 DNA-binding activities. In addition, dasatinib down-regulates expression of
      Stat5 target genes, including Bcl-x, Mcl-1, and cyclin D1. Consistent with these
      results, blockade of Stat5 signaling by dasatinib is accompanied by inhibition of
      cell proliferation and induction of apoptosis. Surprisingly, Stat5 DNA-binding
      activities are enhanced with increasing cell density, which is associated with
      resistance to apoptosis by dasatinib. Our findings indicate that inhibition of
      Stat5 signaling downstream of Bcr-Abl/SFKs contributes to the action of
      dasatinib, and, conversely, that increasing cell density up-regulates Stat5
      activation and confers resistance to dasatinib. Moreover, the level of
      phosphorylated Stat5 in CML cells represents a mechanistically relevant biomarker
      for monitoring inhibition of Bcr-Abl signaling by dasatinib in CML patients using
      convenient immunocytochemical assays.

PMID- 17431119
TI  - Loss of ataxia telangiectasia mutated- and Rad3-related function potentiates the
      effects of chemotherapeutic drugs on cancer cell survival.
AB  - The diverse responses of human cells to various forms of DNA damage are
      controlled by a complex network of signaling proteins. There has been
      considerable interest in the components of this signaling apparatus as potential
      targets for new forms of anticancer therapy. In this report, we examine the
      contributions of an upstream signaling molecule, the ataxia telangiectasia
      mutated- and Rad3-related (ATR) protein kinase, to the resistance of cancer cells
      to DNA-damaging agents that are commonly used as anticancer therapeutics. Loss of
      ATR function in knock-in cancer cells strikingly enhanced the effects of several
      of the most commonly used therapeutic compounds, impeding the progression of the
      cell cycle and reducing long-term cancer cell survival. Loss of ATR function
      potentiated the toxicity of alkylating agents most strikingly, antimetabolites
      moderately, and double-strand break-inducing agents to a lesser extent. These
      results suggest that specific inhibition of ATR activity will be a valid strategy
      to increase the effectiveness of currently used modes of therapy.

PMID- 17431121
TI  - Combined effects of retinoic acid and histone deacetylase inhibitors on human
      neuroblastoma SH-SY5Y cells.
AB  - All-trans retinoic acid (RA) causes differentiation of neuroblastoma cells, and
      retinoids have been used in clinical trials in children with advanced
      neuroblastoma. Combination of RA with histone deacetylase inhibitors (HDACi)
      could result in improved antitumorigenic activity. We have examined the effect of
      the HDACi trichostatin A (TSA), sodium butyrate, and suberoylanilide hydroxamic
      acid (SAHA), alone and in combination with RA in human neuroblastoma SH-SY5Y
      cells. At concentrations that cause sustained increase of histone H3 acetylation,
      HDACi produced extensive apoptotic cell death as shown by flow cytometry analysis
      and induction of poly(ADP-ribose) polymerase proteolysis. HDACi inhibited SH-SY5Y
      cell growth at a much larger extent than RA. This compound did not cause
      apoptosis and did not further increase HDACi-mediated cell death. In contrast,
      both types of drugs cooperated to inhibit cell growth, although synergistic
      effects were not found. In surviving cells, HDACi repressed cyclin D1 expression
      and increased the cyclin kinase inhibitors (CKI) p21(Waf1/Cip1) and p27(Kip1).
      Cyclin D1 was not affected by RA, but this retinoid also increased CKI levels.
      Induction of p21(Waf1/Cip1) and p27(Kip1) by HDACi was further enhanced in the
      presence of RA. This effect seems to be at least partially due to transcriptional
      stimulation of CKI gene expression because both types of drugs cooperated to
      increase CKI mRNA levels and to activate the CKI promoters in transient
      transfection assays. These results show the strong antitumorigenic effects of
      HDACi in neuroblastoma cells and reinforce the idea that combination therapy
      could be useful to inhibit tumor growth.

PMID- 17431120
TI  - Antitumor mechanisms of combined gastrin-releasing peptide receptor and epidermal
      growth factor receptor targeting in head and neck cancer.
AB  - Head and neck squamous cell carcinoma (HNSCC) is characterized by epidermal
      growth factor receptor (EGFR) overexpression, where EGFR levels correlate with
      survival. To date, EGFR targeting has shown limited antitumor effects in head and
      neck cancer when administrated as monotherapy. We previously identified a gastrin
      releasing peptide/gastrin-releasing peptide receptor (GRP/GRPR) aurocrine
      regulatory pathway in HNSCC, where GRP stimulates Src-dependent cleavage of EGFR
      proligands with subsequent EGFR phosphorylation and mitogen-activated protein
      kinase (MAPK) activation. To determine whether GRPR targeting can enhance the
      antitumor efficacy of EGFR inhibition, we investigated the effects of a GRPR
      antagonist (PD176252) in conjunction with an EGFR tyrosine kinase inhibitor
      (erlotinib). Combined blockade of GRPR and EGFR pathways significantly inhibited
      HNSCC, but not immortalized mucosal epithelial cell, proliferation, invasion, and
      colony formation. In addition, the percentage of apoptotic cells increased upon
      combined inhibition. The enhanced antitumor efficacy was accompanied by increased
      expression of cleaved poly(ADP-ribose) polymerase (PARP) and decreased phospho
      EGFR, phospho-MAPK, and proliferating cell nuclear antigen (PCNA). Using reverse
      phase protein microarray (RPPA), we further detected decreased expression of
      phospho-c-Jun, phospho-p70S6K, and phospho-p38 with combined targeting.
      Cumulatively, these results suggest that GRPR targeting can enhance the antitumor
      effects of EGFR inhibitors in head and neck cancer.

PMID- 17431122
TI  - 1alpha,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor
      1/vascular endothelial growth factor pathway in human cancer cells.
AB  - In vitro and in vivo studies have shown that 1alpha,25-dihydroxyvitamin D(3)
      [1,25(OH)(2)D(3)] inhibits angiogenesis in cancer. We now examined whether the
      antiangiogenic effects of 1,25(OH)(2)D(3) are mediated by the hypoxia-inducible
      factor (HIF)-1 pathway. Our results showed that 1,25(OH)(2)D(3) reduces the
      protein expression of both the regulated HIF-1alpha subunit and the vascular
      endothelial growth factor (VEGF) in various human cancer cells. 1,25(OH)(2)D(3)
      also inhibited HIF-1 transcriptional activity (measured by reporter gene assay)
      as well as HIF-1 target genes, including VEGF, ET-1, and Glut-1. We also showed
      that 1,25(OH)(2)D(3) inhibits cell proliferation under hypoxia. Using HIF-1alpha
      knockout colon cancer cells, we show that the inhibition of the hypoxia-induced
      VEGF by 1,25(OH)(2)D(3) is mediated through a HIF-dependent pathway. Because HIF
      1 is a major positive contributor in human tumorigenesis and angiogenesis, we
      believe that its inhibition by 1,25(OH)(2)D(3) strengthens the rationale to use
      vitamin D and its low-calcemic analogues in cancer chemoprevention and therapy.

PMID- 17431123
TI  - Inhibition of nuclear factor-kappaB augments antitumor activity of adenovirus
      mediated melanoma differentiation-associated gene-7 against lung cancer cells via
      mitogen-activated protein kinase kinase kinase 1 activation.
AB  - Nuclear factor-kappaB (NF-kappaB) activation promotes cell survival and growth.
      Reports show that chemotherapeutic agents and cytokines that are used for cancer
      therapy activate NF-kappaB expression in tumor cells and its suppression enhanced
      the antitumor activity. We hypothesized that adenovirus-mediated overexpression
      of melanoma differentiation-associated gene-7/interleukin-24 (Ad-mda7/IL-24)
      induces NF-kappaB expression and that inhibition of this expression results in
      enhanced tumor cell killing. Treatment of human lung tumor (H1299 and A549) cells
      with Ad-mda7 resulted in NF-kappaB activation in a dose- and time-dependent
      manner before activation of cell death pathways. To establish that inhibition of
      Ad-mda7-mediated NF-kappaB activation results in enhanced tumor cell killing,
      H1299 cells that overexpress the dominant-negative I kappa B alpha (dnI kappa B
      alpha) were treated with Ad-mda7 in vitro. An enhanced growth arrest and
      apoptosis was observed in Ad-mda7-treated H1299-dnI kappa B alpha compared with
      H1299-Neo cells. This Ad-mda7-mediated enhanced killing of H1299-dnI kappa B
      alpha cells involved cleavage of mitogen-activated protein kinase kinase kinase 1
      (MEKK1) and caspase-3 in a feedback loop mechanism. The inhibition of MEKK1 or
      caspase-3 cleavage in H1299-dnI kappa B alpha cells resulted in reduced Ad-mda7
      mediated cell killing. In vivo, the treatment of H1299-dnI kappa B alpha s.c.
      tumors with Ad-mda7 resulted in increased drug sensitivity and delayed the tumor
      growth rate compared with Ad-mda7-treated H1299-Neo tumors. Molecular analysis of
      Ad-mda7-treated H1299-dnI kappa B alpha tumors showed increased MEKK1 cleavage
      and activation of caspase-3 compared with Ad-mda7-treated H1299-Neo tumors. Our
      findings thus showed that the NF-kappaB activation induced by Ad-mda7 treatment
      of lung cancer cells is an intrinsic survival mechanism and that the inhibition
      of this NF-kappaB expression results in enhanced tumor cell killing.

PMID- 17431124
TI  - Activation of clinically used anthracyclines by the formaldehyde-releasing
      prodrug pivaloyloxymethyl butyrate.
AB  - The anthracycline group of compounds is extensively used in current cancer
      chemotherapy regimens and is classified as topoisomerase II inhibitor. However,
      previous work has shown that doxorubicin can be activated to form DNA adducts in
      the presence of formaldehyde-releasing prodrugs and that this leads to apoptosis
      independently of topoisomerase II-mediated damage. To determine which
      anthracyclines would be useful in combination with formaldehyde-releasing
      prodrugs, a series of clinically relevant anthracyclines (doxorubicin,
      daunorubicin, idarubicin, and epirubicin) were examined for their capacity to
      form DNA adducts in MCF7 and MCF7/Dx (P-glycoprotein overexpressing) cells in the
      presence of the formaldehyde-releasing drug pivaloyloxymethyl butyrate (AN-9).
      All anthracyclines, with the exception of epirubicin, efficiently yielded adducts
      in both sensitive and resistant cell lines, and levels of adducts were similar in
      mitochondrial and nuclear genomes. Idarubicin was the most active compound in
      both sensitive and resistant cell lines, whereas adducts formed by doxorubicin
      and daunorubicin were consistently lower in the resistant compared with sensitive
      cells. The adducts formed by doxorubicin, daunorubicin, and idarubicin showed the
      same DNA sequence specificity in sensitive and resistant cells as assessed by
      lambda-exonuclease-based sequencing of alpha-satellite DNA extracted from drug
      treated cells. Growth inhibition assays were used to show that doxorubicin,
      daunorubicin, and idarubicin were all synergistic in combination with AN-9,
      whereas the combination of epirubicin with AN-9 was additive. Although apoptosis
      assays indicated a greater than additive effect for epirubicin/AN-9 combinations,
      this effect was much more pronounced for doxorubicin/AN-9 combinations.

PMID- 17431125
TI  - Novel xenograft model expressing human hepatocyte growth factor shows ligand
      dependent growth of c-Met-expressing tumors.
AB  - c-Met, a receptor tyrosine kinase responsible for cellular migration, invasion,
      and proliferation, is overexpressed in human cancers. Although ligand-independent
      c-Met activation has been described, the majority of tumors are ligand dependent
      and rely on binding of hepatocyte growth factor (HGF) for receptor activation.
      Both receptor and ligand are attractive therapeutic targets; however, preclinical
      models are limited because murine HGF does not activate human c-Met. The goal of
      this study was to develop a xenograft model in which human HGF (hHGF) is produced
      in a controllable fashion in the mouse. Severe combined immunodeficient mice were
      treated with adenovirus encoding the hHGF transgene (Ad-hHGF) via tail vein
      injection, and transgene expression was determined by the presence of hHGF mRNA
      in mouse tissue and hHGF in serum. Ad-hHGF administration to severe combined
      immunodeficient mice resulted in hHGF production that was (a) dependent on
      quantity of virus delivered; (b) biologically active, resulting in liver
      hypertrophy; and (c) sustainable over 40 days. In this model, the ligand
      dependent human tumor cell line SW1417 showed enhanced tumor growth, whereas the
      ligand-independent cell lines SW480 and GTL-16 showed no augmented tumor growth.
      This novel xenograft model is ideal for investigating c-Met/HGF-dependent human
      tumor progression and for evaluating c-Met targeted therapy.

PMID- 17431126
TI  - Phospholipid hydroperoxide glutathione peroxidase plays a role in protecting
      cancer cells from docosahexaenoic acid-induced cytotoxicity.
AB  - Docosahexaenoic acid (DHA; 22:6, n-3) is known to exert cytotoxic effects against
      various types of tumors via lipid peroxidation. Whereas several enzymes influence
      the response of cells to oxidative stress, only one enzyme, phospholipid
      hydroperoxide glutathione peroxidase (GPx-4), directly reduces lipid
      hydroperoxides in mammalian cells. The present study was designed to examine the
      involvement of GPx-4 in determining the effects of DHA addition to various human
      cancer cell lines. Although baseline levels of GPx-4 did not correlate with the
      relative sensitivity of human cancer cell lines to DHA, DHA reduced the level of
      protein expression of GPx-4 by at least 50% in all six lines. Knockdown of GPx-4
      by small interfering RNA technique in a human ovarian cancer cell line
      significantly enhanced the cytotoxic effect of DHA in a time- and concentration
      dependent manner. This cytotoxic effect of DHA was reversed by pretreatment with
      vitamin E, suggesting that the enhanced toxicity of GPx-4 knockdown is due to
      changes in the ability of the cells to handle oxidative stress. Neither baseline
      superoxide dismutase-1 nor catalase expression correlated with the relative
      sensitivity of the cells to DHA treatment. These results illustrate that
      susceptibility to the oxidative stress imposed by DHA, and possibly other
      therapeutic agents, is due to complex interactions among multiple antioxidant
      systems. The modulation of GPx-4 levels by DHA administration is of potential
      importance and may influence the cellular response to other oxidant stresses.

PMID- 17431127
TI  - Hepatic colorectal cancer metastases: imaging initial steps of formation in mice.
AB  - PURPOSE: To prospectively use optical imaging to study the cell-specific
      mechanisms of entrapment and subsequent growth of two human colon cancer cell
      lines differing in their propensity to form hepatic metastases. MATERIALS AND
      METHODS: In this Animal Care Committee-approved study, intravital optical imaging
      was performed in exteriorized livers of three groups of mice after intrasplenic
      inoculation of human colon cancer cells. Group 1 mice (control group; n=12)
      received a cell-maintaining solution only. Groups 2 and 3 (n=12 in each) were
      administered poorly (MIP-101 colon cancer cells) or highly (CX-1 colon cancer
      cells) metastatic cells. Imaging was performed on postinoculation days 0, 1, 3,
      and 6 to document sites and mechanisms of tumor cell entrapment and presence and
      sites of endothelial cell activation and of tumor cell interactions with systemic
      macrophages and Kupffer cells. Fluorescence intensity of Kupffer cells was
      compared by using the Mann-Whitney test. Immunohistochemistry served as the
      reference standard for all in vivo observations. RESULTS: Whereas both MIP-101
      and CX-1 colon cancer cells adhered to periportal Kupffer cells, the CX-1 cells
      resulted in Kupffer cell activation, evidenced in vivo by increased visible
      peroxidase activity (P<.05). Only CX-1 cells were associated with subsequent
      downstream endothelial cell activation, evidenced by in vivo expression of E
      selectin. By day 6, regression of periportal MIP-101 tumor growth correlated with
      ingrowth of systemic macrophages, while CX-1 tumor growth, originating in the
      outflow venous regions, correlated with translobular migration and ingrowth of
      activated Kupffer cells. CONCLUSION: Formation of hepatic colon cancer metastases
      is cancer cell-type specific, with cell lines differing in their mechanisms and
      intrahepatic locations of initial entrapment and Kupffer cell activation and
      subsequent growth.

PMID- 17431128
TI  - Basics of imaging informatics. Part 1.
AB  - Imaging informatics is a distinct subspecialty of radiology that endeavors to
      improve the efficiency, accuracy, and reliability of radiologic services within
      the medical enterprise. Although picture archiving and communication systems
      (PACS) are a major focus of imaging informatics, there are many other ways in
      which technology can improve the efficiency of individual radiologists and of the
      entire department. Understanding informatics principles is important because
      these principles affect major purchase decisions, not only for PACS but also for
      other supporting software and for modalities themselves. This review, which is
      the first of two parts, will focus on PACS and its parts and on supporting
      software for PACS.

PMID- 17431129
TI  - Acute cervical traumatic spinal cord injury: MR imaging findings correlated with
      neurologic outcome--prospective study with 100 consecutive patients.
AB  - PURPOSE: To prospectively evaluate whether quantitative and qualitative magnetic
      resonance (MR) imaging assessments after spinal cord injury (SCI) correlate with
      patient neurologic status and are predictive of outcome at long-term follow-up.
      MATERIALS AND METHODS: The study included 100 patients (79 male, 21 female; mean
      age, 45 years; age range, 17-96 years) with traumatic cervical SCI. Ethics
      committee approval and informed consent were obtained. The American Spinal Injury
      Association (ASIA) motor score was used as the outcome measure at admission and
      follow-up. The ASIA impairment scale was used to classify patients according to
      injury severity. Three quantitative (maximum spinal cord compression [MSCC],
      maximum canal compromise [MCC], and lesion length) and six qualitative
      (intramedullary hemorrhage, edema, cord swelling, soft-tissue injury [STI], canal
      stenosis, and disk herniation) imaging parameters were studied. Data were
      analyzed by using the Fisher exact test, the Mantel-Haenszel chi(2) test,
      analysis of variance, analysis of covariance, and stepwise multivariable linear
      regression. RESULTS: Patients with complete motor and sensory SCIs had more
      substantial MCC (P=.005), MSCC (P=.002), and lesion length (P=.005) than did
      patients with incomplete SCIs and those with no SCIs. Patients with complete SCIs
      also had higher frequencies of hemorrhage (P<.001), edema (P<.001), cord swelling
      (P=.001), stenosis (P=.01), and STI (P=.001). MCC (P=.012), MSCC (P=.014), and
      cord swelling (P<.001) correlated with baseline ASIA motor scores. MSCC (P=.028),
      hemorrhage (P<.001), and cord swelling (P=.029) were predictive of the neurologic
      outcome at follow-up. Hemorrhage (P<.001) and cord swelling (P=.002) correlated
      significantly with follow-up ASIA score after controlling for the baseline
      neurologic assessment. CONCLUSION: MSCC, spinal cord hemorrhage, and cord
      swelling are associated with a poor prognosis for neurologic recovery. Extent of
      MSCC is more reliable than presence of canal stenosis for predicting the
      neurologic outcome after SCI.

PMID- 17431130
TI  - Novel RUNX1 isoforms determine the fate of acute myeloid leukemia cells by
      controlling CD56 expression.
AB  - CD56(high) acute myeloid leukemias (AMLs) have a poor prognosis, but it has been
      unclear how CD56 expression is controlled and how it relates to clinical
      aggressiveness. We show that CD56 expression on AML cells correlates with an
      abnormal expression pattern of runt-related transcription factor 1 (RUNX1)
      isoforms. Whereas full-length p48 RUNX1 (p48) up-regulated CD56 in AML cells, 3
      previously unknown shorter RUNX1 isoforms, p38a, p30, and p24, suppressed CD56
      expression. Both p48 and CD56 induced nuclear translocation of nuclear factor
      (NF)-kappaB and increased bcl2L12 expression, and inhibition of this pathway by
      small inhibitory RNA-mediated p48 knock down or NF-kappaB blockade substantially
      increased apoptosis in CD56(+) AML cell lines. These findings indicate the
      potential for new therapy of CD56(high) AML by suppression of the "overactive"
      RUNX1/CD56/NF-kappaB signaling pathway(s).

PMID- 17431131
TI  - Disruption of palladin leads to defects in definitive erythropoiesis by
      interfering with erythroblastic island formation in mouse fetal liver.
AB  - Palladin was originally found up-regulated with NB4 cell differentiation induced
      by all-trans retinoic acid. Disruption of palladin results in neural tube closure
      defects, liver herniation, and embryonic lethality. Here we further report that
      Palld(-/-) embryos exhibit a significant defect in erythropoiesis characterized
      by a dramatic reduction in definitive erythrocytes derived from fetal liver but
      not primitive erythrocytes from yolk sac. The reduction of erythrocytes is
      accompanied by increased apoptosis of erythroblasts and partial blockage of
      erythroid differentiation. However, colony-forming assay shows no differences
      between wild-type (wt) and mutant fetal liver or yolk sac in the number and size
      of colonies tested. In addition, Palld(-/-) fetal liver cells can reconstitute
      hematopoiesis in lethally irradiated mice. These data strongly suggest that
      deficient erythropoiesis in Palld(-/-) fetal liver is mainly due to a compromised
      erythropoietic microenvironment. As expected, erythroblastic island in Palld(-/-)
      fetal liver was found disorganized. Palld(-/-) fetal liver cells fail to form
      erythroblastic island in vitro. Interestingly, wt macrophages can form such units
      with either wt or mutant erythroblasts, while mutant macrophages lose their
      ability to bind wt or mutant erythroblasts. These data demonstrate that palladin
      is crucial for definitive erythropoiesis and erythroblastic island formation and,
      especially, required for normal function of macrophages in fetal liver.

PMID- 17431132
TI  - Enhanced phosphorylation of Nbs1, a member of DNA repair/checkpoint complex Mre11
      RAD50-Nbs1, can be targeted to increase the efficacy of imatinib mesylate against
      BCR/ABL-positive leukemia cells.
AB  - Nbs1, a member of the Mre11-RAD50-Nbs1 complex, is phosphorylated by ATM, the
      product of the ataxia-telangiectasia mutated gene and a member of the
      phosphatidylinositol 3-kinase-related family of serine-threonine kinases, in
      response to DNA double-strand breaks (DSBs) to regulate DNA damage checkpoints.
      Here we show that BCR/ABL stimulated Nbs1 expression by induction of c-Myc
      dependent transactivation and protection from caspase-dependent degradation.
      BCR/ABL-related fusion tyrosine kinases (FTKs) such as TEL/JAK2, TEL/PDGFbetaR,
      TEL/ABL, TEL/TRKC, BCR/FGFR1, and NPM/ALK as well as interleukin 3 (IL-3),
      granulocyte-macrophage colony-stimulating factor (GM-CSF), and stem cell factor
      (SCF) also stimulated Nbs1 expression. Enhanced ATM kinase-dependent
      phosphorylation of Nbs1 on serine 343 (S343) in response to genotoxic treatment
      was detected in leukemia cells expressing BCR/ABL and other FTKs in comparison to
      normal counterparts stimulated with IL-3, GM-CSF, and SCF. Expression of Nbs1
      S343A mutant disrupted the intra-S-phase checkpoint, decreased homologous
      recombinational repair (HRR) activity, down-regulated XIAP expression, and
      sensitized BCR/ABL-positive cells to cytotoxic drugs. Interestingly, inhibition
      of Nbs1 phosphorylation by S343A mutant enhanced the antileukemia effect of the
      combination of imatinib and genotoxic agent.

PMID- 17431133
TI  - Reversal of lead-induced neuronal apoptosis by chelation treatment in rats: role
      of reactive oxygen species and intracellular Ca(2+).
AB  - Lead, a ubiquitous and potent neurotoxicant causes several neurophysiological and
      behavioral alterations. Toxic properties of lead have been attributed to its
      capability to mimic calcium and alter calcium homeostasis. In this study, we have
      addressed the following issues: 1) whether chelation therapy could circumvent the
      altered Ca(2+) homeostasis and prevent neuronal death in chronic lead-intoxicated
      rats, 2) whether chelation therapy could revert altered biochemical and
      behavioral changes, 3) whether combinational therapy using two different
      chelating agents was more advantageous over monotherapy in lead-treated rats, and
      4) what could be the mechanism of neuronal apoptosis. Results indicated that lead
      caused a significant increase in reactive oxygen species, neuronal nitric-oxide
      synthetase, and intracellular free calcium levels along with altered behavioral
      abnormalities in locomotor activity, exploratory behavior, learning, and memory
      that were supported by changes in neurotransmitter levels. A fall in membrane
      potential, release of cytochrome c, and altered bcl(2)/bax ratio indicated
      mitochondrial-dependent apoptosis. Most of these alterations reverted toward
      normal level following combination therapy over monotherapy with calcium disodium
      EDTA (CaNa(2)EDTA) or monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA). It
      could be concluded from our present results that combined therapy with
      CaNa(2)EDTA and MiADMSA might be a better treatment protocol than monotherapy
      with these chelators in lead-induced neurological disorders. We for the first
      time report the role of Ca(2+) in regulating neurological dystrophy caused by
      chronic lead exposure in rats and its recovery with a two-course treatment regime
      of mono or combination therapy.

PMID- 17431135
TI  - Induction by antipsychotics of "win-shift" in the drug discrimination paradigm.
AB  - In a two-lever, food-rewarded drug discrimination paradigm, behavior seems to be
      governed by a win-stay/lose-shift rule; rats continue to press the lever that
      yields food, and, when not rewarded, they shift responding to the alternative
      lever. Here, we report on the effects that antipsychotics and further
      neuropharmacological agents exert in those conditions. At higher doses,
      antipsychotics disrupt most or all behavioral parameters in this paradigm.
      However, at lower doses, rats may select the appropriate lever with normal
      latency and accuracy, obtain a first food pellet (i.e., "win"), and then,
      remarkably, shift responding to the alternative lever ("win-shift"). This
      suggests that antipsychotics can block the effects of reward selectively, i.e.,
      at doses where the initial, secondarily reinforced behavior including the
      initiation of lever pressing, remains intact. Indeed, saline-treated rats that
      are given no reward (i.e., "lose") after having selected a lever, also press the
      alternative lever ("lose-shift"). The induction of selective win-shift is
      specific to antipsychotics, but it varies greatly among them. Perhaps relating to
      its alleged "incisive" action on delirium and hallucinations, and, surprisingly,
      in view of its extrapyramidal actions, acutely administered haloperidol (0.04
      0.08 mg/kg) demonstrates win-shift to an exceptional extent, shared only with the
      newly proposed agent (3-cyclopent-1-enyl-benzyl)-[2-(2,2-dimethyl-2,3-dihydro
      benzofuran-7-yloxy)-ethyl]-amine fumarate (F 15063; 0.31-0.63 mg/kg); the more
      sedative antipsychotic chlorpromazine demonstrated little selectivity. The
      paradigm offers a novel tool to characterize antipsychotics with regard to
      presumably pathogenic motivational processes; mixed D(2)-antagonist/5
      hydroxytryptamine(1A)-agonist agents such as F 15063 may conceivably share the
      powerful antipsychotic action of haloperidol while avoiding the sensitization
      that develops to extrapyramidal effects of haloperidol and consequent negative
      symptoms.

PMID- 17431134
TI  - In vivo effect of venlafaxine on locus coeruleus neurons: role of opioid,
      alpha(2)-adrenergic, and 5-hydroxytryptamine(1A) receptors.
AB  - The locus coeruleus (LC) is involved in several neural pathways responsible for
      some somatic and emotional processes, such as pain and depression; its activity
      is regulated by several receptors, such as opioid, alpha(2)-adrenergic, and 5
      hydroxytryptamine (5-HT)(1A) receptors. The present study investigates the in
      vivo effects of venlafaxine, an antidepressant with analgesic properties, on
      locus coeruleus neurons, and its modulation by opioid, alpha(2)-adrenergic, and 5
      HT(1A) receptors. The results show that acute administration of venlafaxine
      produced a dose-dependent, complete inhibition of LC activity. This inhibitory
      effect was not reversed by the opioid receptor antagonist naloxone, but
      subsequent administration of idazoxan, an alpha(2)-adrenoceptor antagonist, did
      reverse it. The preadministration of the 5-HT(1A) receptor agonist 8-hydroxy-2
      dipropylaminotetralin (8-OH-DPAT) (1 and 40 microg/kg) significantly enhanced the
      venlafaxine inhibitory effect, decreasing the ED(50) by 56 and 44%, respectively.
      A 14-day treatment with venlafaxine (40 mg/kg/day) induced a suppression of the
      firing activity of LC neurons. In these treated animals, venlafaxine produced an
      inhibitory effect similar to that in nontreated animals. This inhibitory effect
      was not reversed by naloxone, but it was reversed by idazoxan. In addition, the
      preadministration of 8-OH-DPAT (40 microg/kg) significantly enhanced the
      venlafaxine effect, decreasing the ED(50) by 60%. These results suggest that the
      effect of venlafaxine on LC neurons is modulated by alpha(2)-adrenergic and 5
      HT(1A) receptors, and not by opioid receptors. These data could contribute to the
      further understanding of the antidepressant and analgesic mechanism of action of
      venlafaxine.

PMID- 17431137
TI  - How the brain translates money into force: a neuroimaging study of subliminal
      motivation.
AB  - Unconscious motivation in humans is often inferred but rarely demonstrated
      empirically. We imaged motivational processes, implemented in a paradigm that
      varied the amount and reportability of monetary rewards for which subjects
      exerted physical effort. We show that, even when subjects cannot report how much
      money is at stake, they nevertheless deploy more force for higher amounts. Such a
      motivational effect is underpinned by engagement of a specific basal forebrain
      region. Our findings thus reveal this region as a key node in brain circuitry
      that enables expected rewards to energize behavior, without the need for the
      subjects;awareness.

PMID- 17431136
TI  - Antibodies to nerve growth factor reverse established tactile allodynia in rodent
      models of neuropathic pain without tolerance.
AB  - A considerable body of evidence implicates endogenous nerve growth factor (NGF)
      in conditions in which pain is a prominent feature, including neuropathic pain.
      However, previous studies of NGF antagonism in animal models of neuropathic pain
      have examined only the prevention of hyperalgesia and allodynia after injury,
      whereas the more relevant issue is whether treatment can provide relief of
      established pain, particularly without tolerance. In the current work, we studied
      the effects of potent, neutralizing anti-NGF antibodies on the reversal of
      tactile allodynia and thermal hyperalgesia in established models of neuropathic
      and inflammatory pain in rats and mice. In the complete Freund's adjuvant-induced
      hind-paw inflammation, spinal nerve ligation and streptozotocin-induced
      neuropathic pain models, a single intraperitoneal injection of a polyclonal anti
      NGF antibody reversed established tactile allodynia from approximately day 3 to
      day 7 after treatment. Effects on thermal hyperalgesia were variable with a
      significant effect observed only in the spinal nerve ligation model. In the mouse
      chronic constriction injury (CCI) model, a mouse monoclonal anti-NGF antibody
      reversed tactile allodynia when administered 2 weeks after surgery. Repeated
      administration of this antibody to CCI mice for 3 weeks produced a sustained
      reversal (days 4 to 21) of tactile allodynia that returned 5 days after the end
      of dosing. In conclusion, NGF seems to play a critical role in models of
      established neuropathic and inflammatory pain in both rats and mice, with no
      development of tolerance to antagonism. Antagonists of NGF, such as fully human
      monoclonal anti-NGF antibodies, may have therapeutic utility in analogous human
      pain conditions.

PMID- 17431138
TI  - Pervasive seismic wave reflectivity and metasomatism of the Tonga mantle wedge.
AB  - Subduction zones play critical roles in the recycling of oceanic lithosphere and
      the generation of continental crust. Seismic imaging can reveal structures
      associated with key dynamic processes occurring in the upper-mantle wedge above
      the sinking oceanic slab. Three-dimensional images of reflecting interfaces
      throughout the upper-mantle wedge above the subducting Tonga slab were obtained
      by migration of teleseismic recordings of underside P- and S-wave reflections.
      Laterally continuous weak reflectors with tens of kilometers of topography were
      detected at depths near 90, 125, 200, 250, 300, 330, 390, 410, and 450
      kilometers. P- and S-wave impedances decreased at the 330-kilometer and 450
      kilometer reflectors, and S-wave impedance decreased near 200 kilometers in the
      vicinity of the slab and near 390 kilometers, just above the global 410-kilometer
      increase. The pervasive seismic reflectivity results from phase transitions and
      compositional zonation associated with extensive metasomatism involving slab
      derived fluids rising through the wedge.

PMID- 17431139
TI  - The increasing dominance of teams in production of knowledge.
AB  - We have used 19.9 million papers over 5 decades and 2.1 million patents to
      demonstrate that teams increasingly dominate solo authors in the production of
      knowledge. Research is increasingly done in teams across nearly all fields. Teams
      typically produce more frequently cited research than individuals do, and this
      advantage has been increasing over time. Teams now also produce the exceptionally
      high-impact research, even where that distinction was once the domain of solo
      authors. These results are detailed for sciences and engineering, social
      sciences, arts and humanities, and patents, suggesting that the process of
      knowledge creation has fundamentally changed.

PMID- 17431140
TI  - Moving the primate debate forward.

PMID- 17431141
TI  - Intellectual property. U.S. Patent Office casts doubt on Wisconsin stem cell
      patents.

PMID- 17431142
TI  - North Korea. A mission to educate the elite.

PMID- 17431143
TI  - U.S. immigration policy. Study finds foreign high-tech workers earn less.

PMID- 17431144
TI  - U.S. academic research. NSF to revisit cost-sharing policies.

PMID- 17431145
TI  - Genetics. Mysterious, widespread obesity gene found through diabetes study.

PMID- 17431146
TI  - Science policy. Japan picks up the 'innovation' mantra.

PMID- 17431147
TI  - Materials science. Chemists mold metal objects from plastic 'nanoputty'.

PMID- 17431148
TI  - Climate change. Global warming is changing the world.

PMID- 17431149
TI  - Immunology. The education of T cells.

PMID- 17431150
TI  - Astronomy. Surveys of exploding stars show one size does not fit all.

PMID- 17431151
TI  - Agriculture. The plant breeder and the pea.

PMID- 17431152
TI  - NIH funding: what does the future look like?

PMID- 17431153
TI  - Are there too many scientists?

PMID- 17431154
TI  - Fishing for good news.

PMID- 17431155
TI  - Comment on "Wetland sedimentation from hurricanes Katrina and Rita".
AB  - Turner et al. (Reports, 20 October 2006, p. 449) measured sedimentation from
      Hurricanes Katrina and Rita in coastal Louisiana and inferred that storm
      deposition overwhelms direct Mississippi River sediment input. However, their
      annualized hurricane deposition rate is overestimated, whereas riverine
      deposition is underestimated by at least an order of magnitude. Their numbers do
      not provide a credible basis for decisions about coastal restoration.

PMID- 17431156
TI  - Environment. Environmental monitoring network for India.

PMID- 17431157
TI  - Medicine. LIGHT hits the liver.

PMID- 17431158
TI  - Chemistry. Femtosecond lasers for molecular measurements.

PMID- 17431160
TI  - Chemistry. Putting order into polymer networks.

PMID- 17431159
TI  - Immunology. The sources of a lipid conundrum.

PMID- 17431161
TI  - Planetary science. As tiny worlds turn.

PMID- 17431162
TI  - Ecology. A positive feedback with negative consequences.

PMID- 17431163
TI  - Retrospective: Frank Albert Cotton (1930-2007).

PMID- 17431165
TI  - Boom time for monkey research.

PMID- 17431166
TI  - Genomicists tackle the primate tree.

PMID- 17431168
TI  - Human-specific changes of genome structure detected by genomic triangulation.
AB  - Knowledge of the rhesus macaque genome sequence enables reconstruction of the
      ancestral state of the human genome before the divergence of chimpanzees.
      However, the draft quality of nonhuman primate genome assemblies challenges the
      ability of current methods to detect insertions, deletions, and copy-number
      variations between humans, chimpanzees, and rhesus macaques and hinders the
      identification of evolutionary changes between these species. Because of the
      abundance of segmental duplications, genome comparisons require the integration
      of genomic assemblies and data from large-insert clones, linkage maps, and
      radiation hybrid maps. With genomic triangulation, an integrative method that
      reconstructs ancestral states and the structural evolution of genomes, we
      identified 130 human-specific breakpoints in genome structure due to
      rearrangements at an intermediate scale (10 kilobases to 4 megabases), including
      64 insertions affecting 58 genes. Comparison with a human structural polymorphism
      database indicates that many of the rearrangements are polymorphic.

PMID- 17431169
TI  - Mobile DNA in Old World monkeys: a glimpse through the rhesus macaque genome.
AB  - The completion of the draft sequence of the rhesus macaque genome allowed us to
      study the genomic composition and evolution of transposable elements in this
      representative of the Old World monkey lineage, a group of diverse primates
      closely related to humans. The L1 family of long interspersed elements appears to
      have evolved as a single lineage, and Alu elements have evolved into four
      currently active lineages. We also found evidence of elevated horizontal
      transmissions of retroviruses and the absence of DNA transposon activity in the
      Old World monkey lineage. In addition, approximately 100 precursors of composite
      SVA (short interspersed element, variable number of tandem repeat, and Alu)
      elements were identified, with the majority being shared by the common ancestor
      of humans and rhesus macaques. Mobile elements compose roughly 50% of primate
      genomes, and our findings illustrate their diversity and strong influence on
      genome evolution between closely related species.

PMID- 17431170
TI  - Demographic histories and patterns of linkage disequilibrium in Chinese and
      Indian rhesus macaques.
AB  - To understand the demographic history of rhesus macaques (Macaca mulatta) and
      document the extent of linkage disequilibrium (LD) in the genome, we partially
      resequenced five Encyclopedia of DNA Elements regions in 9 Chinese and 38 captive
      born Indian rhesus macaques. Population genetic analyses of the 1467 single
      nucleotide polymorphisms discovered suggest that the two populations separated
      about 162,000 years ago, with the Chinese population tripling in size since then
      and the Indian population eventually shrinking by a factor of four. Using
      coalescent simulations, we confirmed that these inferred demographic events
      explain a much faster decay of LD in Chinese (r(2) approximately 0.15 at 10
      kilobases) versus Indian (r(2) approximately 0.52 at 10 kilobases) macaque
      populations.

PMID- 17431171
TI  - Evolutionary formation of new centromeres in macaque.
AB  - A systematic fluorescence in situ hybridization comparison of macaque and human
      synteny organization disclosed five additional macaque evolutionary new
      centromeres (ENCs) for a total of nine ENCs. To understand the dynamics of ENC
      formation and progression, we compared the ENC of macaque chromosome 4 with the
      human orthologous region, at 6q24.3, that conserves the ancestral genomic
      organization. A 250-kilobase segment was extensively duplicated around the
      macaque centromere. These duplications were strictly intrachromosomal. Our
      results suggest that novel centromeres may trigger only local duplication
      activity and that the absence of genes in the seeding region may have been
      important in ENC maintenance and progression.

PMID- 17431172
TI  - Poster: the macaque genome.
AB  - The rhesus macaque (Macaca mulatta) facilitates an extraordinary range of
      biomedical and basic research, and the publication of the genome only makes it a
      more powerful model for studies of human disease; moreover, the macaque's
      position relative to humans and chimpanzees affords the opportunity to learn
      about the processes that have shaped the last 25 million years of primate
      evolution. To allow users to explore these themes of the macaque genome, Science
      has created a special interactive version of the poster published in the print
      edition of the 13 April 2007 issue. The interactive version includes additional
      text and exploration, as well as embedded video featuring seven scientists
      discussing the importance of the macaque and its genome sequence in studies of
      biomedicine and evolution. We have also created an accompanying teaching
      resource, including a lesson plan aimed at teachers of advanced high school life
      science students, for exploring what a comparison of the macaque and human
      genomes can tell us about human biology and evolution. These items are free to
      all site visitors.

PMID- 17431167
TI  - Evolutionary and biomedical insights from the rhesus macaque genome.
AB  - The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged
      from the ancestors of Homo sapiens about 25 million years ago. Because they are
      genetically and physiologically similar to humans, rhesus monkeys are the most
      widely used nonhuman primate in basic and applied biomedical research. We
      determined the genome sequence of an Indian-origin Macaca mulatta female and
      compared the data with chimpanzees and humans to reveal the structure of
      ancestral primate genomes and to identify evidence for positive selection and
      lineage-specific expansions and contractions of gene families. A comparison of
      sequences from individual animals was used to investigate their underlying
      genetic diversity. The complete description of the macaque genome blueprint
      enhances the utility of this animal model for biomedical research and improves
      our understanding of the basic biology of the species.

PMID- 17431173
TI  - A symmetric bipolar nebula around MWC 922.
AB  - We report regular and symmetric structure around dust-enshrouded Be star MWC 922
      obtained with infrared imaging. Biconical lobes that appear nearly square in
      aspect, forming this "Red Square" nebula, are crossed by a series of rungs that
      terminate in bright knots or "vortices," and an equatorial dark band crossing the
      core delimits twin hyperbolic arcs. The intricate yet cleanly constructed forms
      that comprise the skeleton of the object argue for minimal perturbation from
      global turbulent or chaotic effects. We also report the presence of a linear comb
      structure, which may arise from optically projected shadows of a periodic feature
      in the inner regions, such as corrugations in the rim of a circumstellar disk.
      The sequence of nested polar rings draws comparison with the triple-ring system
      seen around the only naked-eye supernova in recent history: SN1987A.

PMID- 17431174
TI  - Quantum structure of the intermolecular proton bond.
AB  - A proton shared between two closed-shell molecules, [A.H+.B], constitutes a
      ubiquitous soft binding motif in biological processes. The vibrational
      transitions associated with the shared proton, which provide a direct probe of
      this interaction, have been extensively studied in the condensed phase but have
      yielded only limited detailed information because of their diffuse character. We
      exploited recent advances in gas-phase ion spectroscopy to identify sharp
      spectral features that can be assigned to both the shared proton and the two
      tethered molecules in a survey of 18 cold, isolated [A.H+.B] ions. These data
      yield a picture of the intermolecular proton bond at a microscopic scale,
      facilitating analysis of its properties within the context of a floppy polyatomic
      molecule.

PMID- 17431175
TI  - Structure of fungal fatty acid synthase and implications for iterative substrate
      shuttling.
AB  - We report crystal structures of the 2.6-megadalton alpha6beta6 heterododecameric
      fatty acid synthase from Thermomyces lanuginosus at 3.1 angstrom resolution. The
      alpha and beta polypeptide chains form the six catalytic domains required for
      fatty acid synthesis and numerous expansion segments responsible for extensive
      intersubunit connections. Detailed views of all active sites provide insights
      into substrate specificities and catalytic mechanisms and reveal their unique
      characteristics, which are due to the integration into the multienzyme. The mode
      of acyl carrier protein attachment in the reaction chamber, together with the
      spatial distribution of active sites, suggests that iterative substrate shuttling
      is achieved by a relatively restricted circular motion of the carrier domain in
      the multifunctional enzyme.

PMID- 17431176
TI  - Plastic and moldable metals by self-assembly of sticky nanoparticle aggregates.
AB  - Deformable, spherical aggregates of metal nanoparticles connected by long-chain
      dithiol ligands self-assemble into nanostructured materials of macroscopic
      dimensions. These materials are plastic and moldable against arbitrarily shaped
      masters and can be thermally hardened into polycrystalline metal structures of
      controllable porosity. In addition, in both plastic and hardened states, the
      assemblies are electrically conductive and exhibit Ohmic characteristics down to
      approximately 20 volts per meter. The self-assembly method leading to such
      materials is applicable both to pure metals and to bimetallic structures of
      various elemental compositions.

PMID- 17431177
TI  - Optimizing the laser-pulse configuration for coherent Raman spectroscopy.
AB  - We introduce a hybrid technique that combines the robustness of frequency
      resolved coherent anti-Stokes Raman scattering (CARS) with the advantages of time
      resolved CARS spectroscopy. Instantaneous coherent broadband excitation of
      several characteristic molecular vibrations and the subsequent probing of these
      vibrations by an optimally shaped time-delayed narrowband laser pulse help to
      suppress the nonresonant background and to retrieve the species-specific signal.
      We used this technique for coherent Raman spectroscopy of sodium dipicolinate
      powder, which is similar to calcium dipicolinate (a marker molecule for bacterial
      endospores, such as Bacillus subtilis and Bacillus anthracis), and we
      demonstrated a rapid and highly specific detection scheme that works even in the
      presence of multiple scattering.

PMID- 17431178
TI  - Designed synthesis of 3D covalent organic frameworks.
AB  - Three-dimensional covalent organic frameworks (3D COFs) were synthesized by
      targeting two nets based on triangular and tetrahedral nodes: ctn and bor. The
      respective 3D COFs were synthesized as crystalline solids by condensation
      reactions of tetrahedral tetra(4-dihydroxyborylphenyl) methane or tetra(4
      dihydroxyborylphenyl)silane and by co-condensation of triangular 2,3,6,7,10,11
      hexahydroxytriphenylene. Because these materials are entirely constructed from
      strong covalent bonds (C-C, C-O, C-B, and B-O), they have high thermal
      stabilities (400 degrees to 500 degrees C), and they also have high surface areas
      (3472 and 4210 square meters per gram for COF-102 and COF-103, respectively) and
      extremely low densities (0.17 grams per cubic centimeter).

PMID- 17431179
TI  - Analyses of soft tissue from Tyrannosaurus rex suggest the presence of protein.
AB  - We performed multiple analyses of Tyrannosaurus rex (specimen MOR 1125) fibrous
      cortical and medullary tissues remaining after demineralization. The results
      indicate that collagen I, the main organic component of bone, has been preserved
      in low concentrations in these tissues. The findings were independently confirmed
      by mass spectrometry. We propose a possible chemical pathway that may contribute
      to this preservation. The presence of endogenous protein in dinosaur bone may
      validate hypotheses about evolutionary relationships, rates, and patterns of
      molecular change and degradation, as well as the chemical stability of molecules
      over time.

PMID- 17431180
TI  - Protein sequences from mastodon and Tyrannosaurus rex revealed by mass
      spectrometry.
AB  - Fossilized bones from extinct taxa harbor the potential for obtaining protein or
      DNA sequences that could reveal evolutionary links to extant species. We used
      mass spectrometry to obtain protein sequences from bones of a 160,000- to 600,000
      year-old extinct mastodon (Mammut americanum) and a 68-million-year-old dinosaur
      (Tyrannosaurus rex). The presence of T. rex sequences indicates that their
      peptide bonds were remarkably stable. Mass spectrometry can thus be used to
      determine unique sequences from ancient organisms from peptide fragmentation
      patterns, a valuable tool to study the evolution and adaptation of ancient taxa
      from which genomic sequences are unlikely to be obtained.

PMID- 17431181
TI  - Lymphotoxin beta receptor-dependent control of lipid homeostasis.
AB  - Hyperlipidemia, one of the most important risk factors for coronary heart
      disease, is often associated with inflammation. We identified lymphotoxin (LT)
      and LIGHT, tumor necrosis factor cytokine family members that are primarily
      expressed on lymphocytes, as critical regulators of key enzymes that control
      lipid metabolism. Dysregulation of LIGHT expression on T cells resulted in
      hypertriglyceridemia and hypercholesterolemia. In low-density lipoprotein
      receptor-deficient mice, which lack the ability to control lipid levels in the
      blood, inhibition of LT and LIGHT signaling with a soluble lymphotoxin beta
      receptor decoy protein attenuated the dyslipidemia. These results suggest that
      the immune system directly influences lipid metabolism and that LT modulating
      agents may represent a novel therapeutic route for the treatment of dyslipidemia.

PMID- 17431182
TI  - Structural basis for substrate delivery by acyl carrier protein in the yeast
      fatty acid synthase.
AB  - In the multifunctional fungal fatty acid synthase (FAS), the acyl carrier protein
      (ACP) domain shuttles reaction intermediates covalently attached to its
      prosthetic phosphopantetheine group between the different enzymatic centers of
      the reaction cycle. Here, we report the structure of the Saccharomyces cerevisiae
      FAS determined at 3.1 angstrom resolution with its ACP stalled at the active site
      of ketoacyl synthase. The ACP contacts the base of the reaction chamber through
      conserved, charge-complementary surfaces, which optimally position the ACP toward
      the catalytic cleft of ketoacyl synthase. The conformation of the prosthetic
      group suggests a switchblade mechanism for acyl chain delivery to the active site
      of the enzyme.

PMID- 17431183
TI  - Structural insight into pre-B cell receptor function.
AB  - The pre-B cell receptor (pre-BCR) serves as a checkpoint in B cell development.
      In the 2.7 angstrom structure of a human pre-BCR Fab-like fragment, consisting of
      an antibody heavy chain (HC) paired with the surrogate light chain, the "unique
      regions" of VpreB and lambda5 replace the complementarity-determining region 3
      (CDR3) loop of an antibody light chain and appear to "probe" the HC CDR3,
      potentially influencing the selection of the antibody repertoire. Biochemical
      analysis indicates that the pre-BCR is impaired in its ability to recognize
      antigen, which, together with electron microscopic visualization of a pre-BCR
      dimer, suggests ligand-independent oligomerization as the likely signaling
      mechanism.

PMID- 17431184
TI  - Elevated Lp-PLA2 levels add prognostic information to the metabolic syndrome on
      incidence of cardiovascular events among middle-aged nondiabetic subjects.
AB  - BACKGROUND: To explore potential interrelationships between lipoprotein
      associated phospholipase A2 (Lp-PLA2), the metabolic syndrome (MetS), and
      incident cardiovascular disease (CVD). METHODS AND RESULTS: MetS was defined by
      the National Cholesterol Education Program Adult treatment Panel III criteria in
      4480 nondiabetic Malmo Diet and Cancer Study subjects without history of CVD.
      Incidence of first CVD event (stroke [130 cases] or myocardial infarction [131])
      was monitored over 10 years of follow-up. Lp-PLA2 activity and mass were
      significantly higher in subjects with MetS. Lp-PLA2 activity compared with Lp
      PLA2 mass was more strongly correlated to individual components and increased
      more linearly with number of MetS components. Elevated Lp-PLA2 activity (top
      compared with bottom tertile), but not elevated Lp-PLA2 mass, increased risk for
      incident CVD (relative risk, RR: 1.54, 95% CI 1.07 to 2.24), as did MetS (1.42,
      1.06 to 1.90) after taking possible confounders into account. Relative to those
      without either elevated Lp-PLA2 activity or MetS, combination of MetS and
      elevated Lp-PLA2 activity increased risk for CVD (1.97, 1.34 to 2.90). Elevated
      Lp-PLA2 activity without MetS increased risk for CVD (1.40, 1.03 to 1.92) but not
      MetS without elevated Lp-PLA2 activity (1.46, 0.94 to 2.27). CONCLUSION: Lp-PLA2
      is associated to the MetS. Higher plasma levels of Lp-PLA2 increased risk for
      incident CVD regardless of MetS. The simultaneous presence of elevated Lp-PLA2
      activity and MetS may identify an especially high risk individual.

PMID- 17431185
TI  - Fenofibrate effect on triglyceride and postprandial response of apolipoprotein A5
      variants: the GOLDN study.
AB  - OBJECTIVE: Apolipoprotein A5 (APOA5) is a key determinant of plasma triglyceride
      (TG) concentrations. Genetic variation at the APOA5 locus could be responsible
      for some of the observed differences in response to fenofibrate therapy. METHODS
      AND RESULTS: We examined the association between tag SNPs (-1131T>C and 56C>G) at
      APOA5 and TG and HDL-C response to fenofibrate and a postprandial lipid challenge
      in 791 men and women participating in the GOLDN study. After 3-week drug
      treatment, APOA5 56G carriers displayed significant decrease in TG (P=0.006), and
      increase in HDL-C (P=0.002) levels relative to their basal values in the fasting
      state when compared with noncarriers (a TG reduction of -35.8+/-2.8% versus 
      27.9+/-0.9% and a HDL-C increase of 11.8+/-1.3% versus 6.9+/-0.5%, respectively).
      In the postprandial lipemia after a fat load, the 56G carriers showed a
      significant decrease in the area under curve for TG and increase for HDL-C than
      the noncarriers. These diverse beneficial responses of 56G carriers to
      fenofibrate were further characterized by a higher increase in large LDL-C
      concentrations and LDL size. On the other hand, subjects with different APOA5
      1131T>C genotypes showed no significant response to fenofibrate intervention.
      CONCLUSION: This study suggests that the APOA5 56G carriers benefited more from
      the fenofibrate treatment than noncarriers in lowering plasma TG and increasing
      HDL-C levels.

PMID- 17431186
TI  - Glutaredoxin mediates Akt and eNOS activation by flow in a glutathione reductase
      dependent manner.
AB  - OBJECTIVE: The glutathione (GSH)/glutaredoxin (Grx) system regulates activities
      of many redox sensitive enzymes. This system has been shown to protect cells from
      hydrogen peroxide-induced apoptosis by regulating the redox state of Akt. Grx can
      be regulated by redox state; the oxidized Grx is selectively recycled to the
      reduced form by GSH. Flow can maintain endothelial cells in a reduced state by
      activating glutathione reductase (GR) and increasing the GSH/GSSG ratio. Because
      steady laminar flow exerts an antioxidant effect, we hypothesized that Grx
      mediates flow induced Akt and eNOS phosphorylation in a GR dependent manner.
      METHODS AND RESULTS: Exposure of endothelial cells (ECs) to physiological steady
      laminar flow (shear stress=12 dyn/cm2) for 5 minutes significantly increased Grx
      activity (1.9+/-0.2-fold), and also increased Akt and eNOS phosphorylation.
      Overexpression of GFP-GR in ECs significantly increased Grx activity by 1.6+/-0.1
      fold. Pretreatment with the GR inhibitor 1,3-bis[2-chloroethyl]-1-nitrosourea
      (BCNU) for 30 minutes dramatically reduced Grx activity and inhibited the
      increase in Akt and eNOS phosphorylation induced by flow. Overexpression of wild
      type Grx in ECs increased both Akt and eNOS phosphorylation. In contrast, a
      mutated Grx (C22S/C25S), which lacks thioltransferase activity, had no effect.
      Therefore, flow-induced Akt and eNOS phosphorylation depend on Grx
      thioltransferase activity. Downregulation of Grx by small interfering RNA
      decreased flow induced Akt and eNOS phosphorylation. CONCLUSIONS: These data
      suggest that Grx is an important mediator for flow-induced Akt and eNOS
      activation, and Grx activity depends on GR-mediated changes in EC redox state.

PMID- 17431187
TI  - Induction of vascular permeability by the sphingosine-1-phosphate receptor-2
      (S1P2R) and its downstream effectors ROCK and PTEN.
AB  - OBJECTIVES: S1P acts via the S1PR family of G protein-coupled receptors to
      regulate a variety of physiological responses. Whereas S1P1R activates G(i)- and
      PI-3-kinase-dependent signals to inhibit vascular permeability, the related S1P2R
      inhibits the PI-3-kinase pathway by coupling to the Rho-dependent activation of
      the PTEN phosphatase. However, cellular consequences of S1P2R signaling in the
      vascular cells are not well understood. METHODS AND RESULTS: Selective signaling
      of the S1P2R was achieved by adenoviral-mediated expression in endothelial cells.
      Secondly, endogenously expressed S1P2R was blocked by the specific
      pharmacological antagonist JTE013. Activation of S1P2R in endothelial cells
      resulted in Rho-ROCK- and PTEN-dependent disruption of adherens junctions,
      stimulation of stress fibers, and increased paracellular permeability. JTE013
      treatment of naive endothelial cells potentiated the S1P1R-dependent effects such
      as formation of cortical actin, blockade of stress fibers, stimulation of
      adherens junction assembly, and improved barrier integrity. This observation was
      extended to the in vivo model of vascular permeability in the rat lung: the S1P2R
      antagonist JTE013 significantly inhibited H2O2-induced permeability in the rat
      lung perfused model. CONCLUSIONS: S1P2R activation in endothelial cells increases
      vascular permeability. The balance of S1P1 and S1P2 receptors in the endothelium
      may determine the regulation of vascular permeability by S1P.

PMID- 17431188
TI  - Dietary fat-induced alterations in atherosclerosis are abolished by ACAT2
      deficiency in ApoB100 only, LDLr-/- mice.
AB  - OBJECTIVES: The enzyme acyl-coenzymeA (CoA):cholesterol O-acyltransferase 2
      (ACAT2) in the liver synthesizes cholesteryl esters (CE) from cholesterol and
      fatty acyl-CoA, which get incorporated into apoB-containing lipoproteins that are
      secreted into the bloodstream. Dietary fatty acid composition influences the
      amount and fatty acid composition of CE within apoB-containing lipoproteins. We
      hypothesized that when ACAT2 activity is removed by gene deletion, hepatic CE
      synthesis and secretion would be minimal and, as a result, dietary fat-related
      differences in atherosclerosis would be eliminated. METHODS AND RESULTS: Groups
      of female apoB100 only, LDLr-/- mice with and without ACAT2 were fed diets
      enriched in either omega-3 or omega-6 polyunsaturated fat, saturated fat, and cis
      or trans monounsaturated fat. After 20 weeks on diet, mice fed diets enriched in
      monounsaturated or saturated fat exhibited significantly higher amounts of plasma
      cholesterol, larger LDL particles enriched in monounsaturated CE, and more
      atherosclerosis than mice fed polyunsaturated fat. The dietary fat-induced shifts
      in plasma cholesterol, LDL size, LDL CE composition, and atherosclerosis were not
      observed in ACAT2-/- mice. Regardless of the diet fed, the ACAT2-/- mice were
      protected from atherosclerosis. CONCLUSIONS: The results indicate that in apoB100
      only, LDLr-/- mice, ACAT2 plays an essential role in facilitating dietary fat
      type-specific atherosclerosis through its various effects on plasma lipoprotein
      concentration and composition.

PMID- 17431189
TI  - Carotid chemoreceptor modulation of regional blood flow distribution during
      exercise in health and chronic heart failure.
AB  - Previous work has shown sensitization of carotid chemoreceptor (CC)
      responsiveness during exercise as well as in chronic heart failure (CHF).
      Accordingly, we hypothesized that the CCs contribute to the sympathetic restraint
      of skeletal muscle blood flow during exercise and CHF. We examined the effect of
      transient CC inhibition on total (Con(T)) and hindlimb (Con(L)) conductance, and
      blood pressure at rest and during exercise (2.5 miles per hour, 5% grade) in
      chronically instrumented dogs. Via a carotid arterial catheter, CCs were
      inhibited using dopamine (5 to 10 microg/kg) or hyperoxic lactated Ringer's
      solution. Although vasodilation did not occur with CC inhibition in resting
      healthy dogs, CC inhibition during exercise caused an immediate vasodilatory
      response (increase in Con(T) and Con(L) and decrease in blood pressure). When
      comparing the peak Con(L) response from CC inhibition versus alpha-adrenergic
      blockade (phentolamine), we found that the CCs accounted for approximately one
      third of the total sympathetic restraint during exercise. CHF was then induced by
      chronic rapid cardiac pacing and characterized by impaired cardiac function,
      enhanced chemosensitivity, and greater sympathetic restraint at rest and during
      exercise. In contrast to healthy dogs, CC inhibition in resting CHF dogs produced
      vasodilation, whereas a similar vasodilatory response was observed during
      exercise in CHF as compared with healthy dogs. The vasodilation following CC
      inhibition during exercise and in CHF was abolished with alpha-adrenergic
      blockade and was absent in healthy exercising animals after carotid body
      denervation. These results establish an important role for the CCs in
      cardiovascular control in the healthy animal during exercise and in the CHF
      animal both at rest and during exercise.

PMID- 17431190
TI  - Mechanisms of TGF-beta1-induced intimal growth: plasminogen-independent
      activities of plasminogen activator inhibitor-1 and heterogeneous origin of
      intimal cells.
AB  - Transforming growth factor (TGF)-beta(1) is a potent stimulator of intimal
      growth. We showed previously that TGF-beta(1) stimulates intimal growth through
      early upregulation of plasminogen activator inhibitor-1 (PAI-1) and,
      subsequently, PAI-1-dependent increases in cell migration and matrix
      accumulation. We also showed that PAI-1 negatively regulates TGF-beta(1)
      expression in the artery wall. Here we use plasminogen-deficient mice to test
      whether TGF-beta(1)-stimulated, PAI-1-dependent intimal growth and PAI-1
      suppression of TGF-beta(1) expression are mediated through inhibition of
      plasminogen activation by PAI-1. We also use lineage tracing to investigate the
      origin of cells in TGF-beta(1)-induced intimas. Surprisingly, both TGF-beta(1)
      induced, PAI-1-dependent intimal growth and PAI-1 suppression of TGF-beta(1)
      expression are independent of plasminogen. Moreover, approximately 50% of cells
      that migrate into the intima of TGF-beta(1)-overexpressing arteries carry a
      smooth muscle lineage marker, <1% carry a bone marrow lineage marker, and the
      remaining cells carry neither marker. Therefore, PAI-1 stimulates intimal growth
      and suppresses TGF-beta(1) expression through activities other than inhibition of
      plasminogen activation. In addition, contrary to widely held models, our results
      do not support a role for plasmin (or thrombospondin) in TGF-beta(1) activation
      in the artery wall. Further identification of the molecular targets through which
      PAI-1 stimulates intimal formation and suppresses TGF-beta(1) expression in the
      artery wall may reveal new approaches for inhibiting intimal formation. Our
      studies also discount bone marrow as an important source from which TGF-beta(1)
      recruits intimal cells and suggest instead that TGF-beta(1) induces substantial
      cell migration either from the adventitia or from an extravascular, but
      nonhematopoietic source.

PMID- 17431191
TI  - Triglyceride-rich lipoproteins from normotrygliceridemic subjects and
      hyperlipidemic patients differently affect endothelial cell activation and gene
      expression patterns.

PMID- 17431192
TI  - Closing the gap at hot spots.

PMID- 17431193
TI  - The skinny on TRPV1.

PMID- 17431194
TI  - Exercise after myocardial infarction improves contractility and decreases
      myofilament Ca2+ sensitivity.

PMID- 17431195
TI  - A candidate hypertension gene: will SPON1 hold salt and water?

PMID- 17431196
TI  - Building the right ventricle.

PMID- 17431197
TI  - cAMP-Specific phosphodiesterase-4 enzymes in the cardiovascular system: a
      molecular toolbox for generating compartmentalized cAMP signaling.
AB  - Cyclic AMP regulates a vast number of distinct events in all cells. Early studies
      established that its hydrolysis by cyclic nucleotide phosphodiesterases (PDEs)
      controlled both the magnitude and the duration of its influence. Recent evidence
      shows that PDEs also act as coincident detectors linking cyclic-nucleotide- and
      non-cyclic-nucleotide-based cellular signaling processes and are tethered with
      great selectively to defined intracellular structures, thereby integrating and
      spatially restricting their cellular effects in time and space. Although 11
      distinct families of PDEs have been defined, and cells invariably express
      numerous individual PDE enzymes, a large measure of our increased appreciation of
      the roles of these enzymes in regulating cyclic nucleotide signaling has come
      from studies on the PDE4 family. Four PDE4 genes encode more than 20 isoforms.
      Alternative mRNA splicing and the use of different promoters allows cells the
      possibility of expressing numerous PDE4 enzymes, each with unique amino-terminal
      targeting and/or regulatory sequences. Dominant negative and small interfering
      RNA-mediated knockdown strategies have proven that particular isoforms can
      uniquely control specific cellular functions. Thus the protein kinase A
      phosphorylation status of the beta(2) adrenoceptor and, thereby, its ability to
      switch its signaling to extracellular signal-regulated kinase activation, is
      uniquely regulated by PDE4D5 in cardiomyocytes. We describe how cardiomyocytes
      and vascular smooth muscle cells selectively vary both the expression and the
      catalytic activities of PDE4 isoforms to regulate their various functions and how
      altered regulation of these processes can influence the development, or
      resolution, of cardiovascular pathologies, such as heart failure, as well as
      various vasculopathies.

PMID- 17431198
TI  - Vascular remodeling in transplant vasculopathy.
AB  - As therapeutic strategies to prevent acute rejection progressively improve,
      transplant vasculopathy (TV) constitutes the single most important limitation for
      long-term functioning of solid organ allografts. In TV, allograft arteries
      characteristically develop severe, diffuse intimal hyperplastic lesions that
      eventually compromise luminal flow and cause ischemic graft failure. Traditional
      immunosuppressive strategies that check acute allograft rejection do not prevent
      TV; indeed 50% of transplant recipients will have significant disease within five
      years of organ transplantation, and 90% will have significant TV a decade after
      their surgery. TV can involve the entire length of the transplanted arterial bed,
      including penetrating intraorgan arterioles. Indeed, the luminal narrowing of
      such penetrating vessels may be the most functionally significant because
      arterioles represent the major contributors to tissue vascular resistance.
      Because of the diffuseness of TV involvement in the allograft vascular bed, the
      only currently definitive therapy requires re-transplantation. Nevertheless, as
      we better understand the pathogenesis and critical mediators of these lesions,
      pharmacological advances can be anticipated. Other articles in this thematic
      review series focus on the specifics of the inciting injury, the cytokines and
      chemokines that drive TV development, and the nature of the recruited cells in TV
      lesions, as well as the pathogenic similarities between TV and other vascular
      lesions such as atherosclerosis. This review focuses on the mechanisms of
      vascular wall remodeling in TV, including the intimal accumulation of smooth
      muscle-like cells and associated extracellular matrix, medial smooth muscle cell
      degeneration, and adventitial fibrosis. A brief overview highlights the
      aneurysmal changes that can accrue when vessel wall inflammation has a cytokine
      profile distinct from the typical proinflammatory interferon-gamma-dominated
      milieu.

PMID- 17431199
TI  - In vivo thrombus formation in murine models.
AB  - Platelets play a central role in hemostasis, but also in atherothrombosis, as
      they rapidly adhere to tissue and to one another as a response to any vascular
      injury. This process involves a large number of surface receptors, signaling
      pathways, and enzymatic cascades as well as their complex interplay. Although in
      vitro experiments proved successful in both identifying new receptors and
      pathways and developing potent and selective antithrombotic drugs, in vitro
      research cannot mimic the myriad hemodynamic and spatiotemporal cellular and
      molecular interactions that occur during the generation and propagation of
      thrombi in vivo. Animal models, and, with the availability of genetically
      modified mouse strains and of modern intravital imaging techniques, mouse models
      in particular, have opened new ways to identify both individual roles and the
      interplay of platelet proteins in complex in vivo settings. In vivo models
      revealed the important role of, eg, Gas6 or blood coagulation factor XII in
      thrombus formation, and results obtained in in vivo models raised the interesting
      possibility that (physiologic) hemostasis and (pathologic) thrombosis might
      represent 2 mechanistically different processes. This review summarizes in vivo
      findings that contributed significantly to our understanding of hemostatic and
      thrombotic processes and which may help to guide future research.

PMID- 17431200
TI  - Should stroke be considered both a brain attack and a heart attack?

PMID- 17431201
TI  - Timing of neuropsychological outcome measures in patients with subarachnoid
      hemorrhage.

PMID- 17431202
TI  - Thrombolysis for acute stroke in pediatrics.

PMID- 17431203
TI  - Making the most of secondary prevention.

PMID- 17431204
TI  - Guidelines for the early management of adults with ischemic stroke: a guideline
      from the American Heart Association/American Stroke Association Stroke Council,
      Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council,
      and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes
      in Research Interdisciplinary Working Groups: the American Academy of Neurology
      affirms the value of this guideline as an educational tool for neurologists.
AB  - PURPOSE: Our goal is to provide an overview of the current evidence about
      components of the evaluation and treatment of adults with acute ischemic stroke.
      The intended audience is physicians and other emergency healthcare providers who
      treat patients within the first 48 hours after stroke. In addition, information
      for healthcare policy makers is included. METHODS: Members of the panel were
      appointed by the American Heart Association Stroke Council's Scientific Statement
      Oversight Committee and represented different areas of expertise. The panel
      reviewed the relevant literature with an emphasis on reports published since 2003
      and used the American Heart Association Stroke Council's Levels of Evidence
      grading algorithm to rate the evidence and to make recommendations. After
      approval of the statement by the panel, it underwent peer review and approval by
      the American Heart Association Science Advisory and Coordinating Committee. It is
      intended that this guideline be fully updated in 3 years. RESULTS: Management of
      patients with acute ischemic stroke remains multifaceted and includes several
      aspects of care that have not been tested in clinical trials. This statement
      includes recommendations for management from the first contact by emergency
      medical services personnel through initial admission to the hospital. Intravenous
      administration of recombinant tissue plasminogen activator remains the most
      beneficial proven intervention for emergency treatment of stroke. Several
      interventions, including intra-arterial administration of thrombolytic agents and
      mechanical interventions, show promise. Because many of the recommendations are
      based on limited data, additional research on treatment of acute ischemic stroke
      is needed.

PMID- 17431205
TI  - Metabolic syndrome and the risk of ischemic heart disease and stroke among
      Japanese men and women.
AB  - BACKGROUND AND PURPOSE: Limited evidence was available on the metabolic syndrome
      and risk of cardiovascular disease in Asia. The purpose of this study is to
      examine the association of the metabolic syndrome and risk of ischemic
      cardiovascular disease in Japanese men and women. METHODS: We conducted an 18
      year prospective study of 9087 Japanese people aged 40 to 69 years (3595 men and
      5492 women), initially free of ischemic heart disease or stroke. During follow
      up, there were 116 (74 men and 42 women) cases of ischemic heart disease and 256
      (144 men and 112 women) ischemic strokes. Metabolic syndrome was defined by the
      modified criteria of the National Cholesterol Education Program Adult Treatment
      Panel III (NCEP/ATPIII), with the presence of >/=3 of the following factors: (1)
      serum triglycerides >/=1.69 mmol/L (150 mg/dL); (2) HDL-cholesterol <1.03 mmol/L
      (40 mg/dL) for men and <1.29 mmol/L (50 mg/dL) for women; (3) glucose >/=6.11
      mmol/L (110 mg/dL) fasting or >/=7.77 mmol/L (140 mg/dL) nonfasting, or on
      treatment; (4) blood pressure > or =130/85 mm Hg or medication use, and (5) body
      mass index >/=25.0 kg/m(2). RESULTS: For both sexes, high blood pressure, high
      triglycerides and low HDL cholesterol were associated with increased risks of
      ischemic heart disease or stroke after adjustment for cardiovascular risk
      factors. A dose-response relationship was found between the number of metabolic
      risk factors and incidence of these cardiovascular end points. The multivariable
      hazard ratio (95% CI) associated with metabolic syndrome was 2.4 (1.4 to 4.0) in
      men and 2.3 (1.2 to 4.3) in women for ischemic heart disease, and 2.0 (1.3 to
      3.1) and 1.5 (1.0 to 2.3), respectively, for ischemic stroke. The contribution of
      metabolic syndrome to the risks was independent of serum total cholesterol levels
      but stronger among smokers. CONCLUSIONS: The metabolic syndrome is a major
      determinant of ischemic cardiovascular disease among middle-aged Japanese men and
      women, in particular among smokers.

PMID- 17431206
TI  - Risk of myocardial infarction or vascular death after first ischemic stroke: the
      Northern Manhattan Study.
AB  - BACKGROUND AND PURPOSE: In national guidelines, absolute long-term risk of
      myocardial infarction (MI) or coronary death determines target low-density
      lipoprotein levels, but stroke patients are not explicitly addressed. We
      determined the absolute 5-year risk of cardiovascular outcomes and their
      predictors after first ischemic stroke in a multiethnic cohort. METHODS: A
      population-based cohort of first ischemic stroke patients > or =40 years old was
      prospectively followed annually for recurrent stroke, MI and cause-specific
      mortality. Kaplan-Meier 5-year risks for MI or vascular death (primary outcome),
      and other cardiovascular events, were calculated. Univariate and multivariate Cox
      proportional hazards models were used to calculate hazard ratios and 95% CI for
      predictors of cardiovascular outcomes. RESULTS: Mean age (n=655) was 69.7+/-12.7
      years; 55.4% of participants were women, and 51.3% Hispanic. The 5-year risk of
      MI or vascular death was 17.4% (95% CI, 14.2% to 20.6%). Independent historical
      predictors of MI or vascular death were age >70 years (hazard ratio 1.62, 1.07 to
      2.44), history of coronary artery disease (hazard ratio 1.76, 1.13 to 2.74), and
      atrial fibrillation (hazard ratio 1.76, 1.05 to 2.94). In the lowest risk group,
      those < or =70 years old without coronary artery disease, 5-year risk of MI or
      vascular death was 9.7%. CONCLUSIONS: The absolute risk of MI or vascular death
      after ischemic stroke, even in those without high-risk features, approximates
      levels used by national organizations to designate groups of patients at high
      risk of vascular events. The comparability of levels of absolute risk among
      stroke and cardiac patients may have treatment implications.

PMID- 17431207
TI  - Assessment of emergency medical technicians serving the Phoenix metropolitan
      matrix of primary stroke centers.

PMID- 17431209
TI  - Combining multiple approaches for the secondary prevention of vascular events
      after stroke: a quantitative modeling study.
AB  - BACKGROUND AND PURPOSE: Numerous effective strategies for the secondary
      prevention of cardiovascular events in high-risk patients have now been
      established. We sought to calculate the cumulative benefit of combining multiple
      strategies for preventing recurrent events in patients with a history of ischemic
      stroke or transient ischemic attack. METHODS: A comprehensive literature search
      was undertaken to identify meta-analyses of randomized controlled trials
      reporting on the efficacy of secondary prevention strategies. The baseline
      incidence of vascular events was modeled from the Life Long After Cerebral
      Ischemia study. Strategies were combined on a multiplicative scale and cumulative
      risk reductions were computed over a 5-year interval. RESULTS: The combination of
      5 proven strategies applied to survivors of an initial stroke or transient
      ischemic attack--dietary modification, exercise, aspirin, a statin, and an
      antihypertensive agent--could result in a cumulative relative risk reduction of
      80%. Given a 5-year major cardiovascular event rate of 24%, this translates to a
      number needed to treat of about 5. Further gains would result from applying
      multimodality therapy over longer intervals and enriching the base strategy with
      dual antiplatelet therapy, high-dose statins, and more intensive blood pressure
      lowering. Even more benefit would be present in high-risk subgroups with the
      addition, where appropriate, of carotid endarterectomy, moderate intensity oral
      anticoagulants, glycemic control, and smoking cessation. CONCLUSIONS: At least
      four-fifths of recurrent vascular events in patients with cerebrovascular disease
      might be prevented by application of a comprehensive, multifactorial approach.

PMID- 17431210
TI  - Thrombolysis for ischemic stroke in children: data from the nationwide inpatient
      sample.
AB  - BACKGROUND AND PURPOSE: Few pediatric reports of thrombolysis exist. We sought to
      determine national rates of thrombolysis among pediatric ischemic stroke patients
      using a national database. METHODS: Patients between the ages of 1 and 17 years,
      entered in the Nationwide Inpatient Sample between 2000 and 2003, with
      International Classification of Diseases codes for ischemic stroke were included
      in the study. Differences in mean age, gender distribution, ethnicity, secondary
      diagnoses, medical complications, associated procedure rates, modes of discharge,
      and hospital costs between pediatric stroke patients receiving and not receiving
      thrombolysis were estimated. RESULTS: In the United States, between 2000 and 2003
      an estimated 2904 children were admitted with ischemic stroke, of which 46
      children (1.6%) received thrombolytic therapy. Children who received thrombolysis
      were on the average older (11 versus 9 years), more likely to be male (100%
      versus 53.8%), with significantly higher hospital costs ($81,800 versus $38,700).
      These children were also less likely to be discharged home with higher rates of
      death and dependency, although differences in clinical severity between the 2
      groups was not known. CONCLUSIONS: Thrombolysis, though not indicated for
      patients <18 years of age, is currently being administered to children, with
      unclear benefit. Larger studies are needed to evaluate the safety and efficacy of
      this treatment for children.

PMID- 17431211
TI  - Depressive disorders after 20 months in elderly stroke patients: a case-control
      study.
AB  - BACKGROUND AND PURPOSE: Depression is common after stroke. Reported frequencies
      vary widely between studies because of differences in patient selection, time
      from stroke to assessment, evaluation methods and diagnostic criteria. Poststroke
      depression is related to increased mortality and poorer rehabilitation outcome.
      Few studies have been done in the elderly, and there is a lack of studies with
      population-based controls. We aimed to examine the risk of depression in elderly
      patients one and a half years after stroke and to compare the risk with a
      population-based control sample. METHODS: We examined 149 elderly stroke
      survivors and 745 age- and sex-matched controls from the general population with
      semistructured psychiatric examinations and cognitive assessments. Diagnoses were
      made according to DSM-III-R. Independent samples t test and chi(2) test were used
      to test for significance, Mantel-Haenszel odds ratios with 95% CI for relative
      risk and Tarone statistics for risk differences between groups. RESULTS: The
      frequency of depression was 34% in stroke patients and 13% in population controls
      (odds ratio, 3.4; 95% CI, 2.3 to 5.0). The risk of depression was increased in
      both men and women and in all age groups but not related to the predominant side
      of stroke symptoms. CONCLUSIONS: Depression is common after stroke. It is
      therefore important to identify depression in stroke patients because it is a
      treatable condition that may have implications for poorer outcome in relation to
      rehabilitation and mortality.

PMID- 17431212
TI  - Cytokine modulation of muscarinic receptors in the murine intestine.
AB  - The extent to which gut motility and smooth muscle contractility are altered by
      intestinal inflammation depends on the nature of the underlying immune
      activation. The muscarinic receptor on smooth muscle plays a critical role in
      mediating acetylcholine-driven motor function. We examined the ability of
      cytokines to influence muscarinic receptor characteristics on intestinal
      longitudinal muscle and related the findings to studies on carbachol-induced
      contraction. Cells were isolated from longitudinal muscle myenteric plexus
      (LMMP). Cytokine receptor expression, muscle contractility, and muscarinic
      agonist receptor characteristics were examined by agonist displacement of [N
      methyl-(3)H]scopolamine ([(3)H]NMS) binding. The TGF-beta1 receptor (543 bp) and
      the IFN-gamma receptor 1 (660 bp) were identified on smooth muscle cells.
      Scatchard analysis revealed dissociation constant and maximum binding values for
      [(3)H]NMS of 2.6 nM and 2.4 x 10(4) sites/cell, respectively, in control cells.
      Nematode infection was accompanied by a reduction in inhibitory constant of the
      high-affinity sites (K(H)), and this was independent of signal transduction and
      activator of transcription 6. Preincubation with TGF-beta1 enhanced longitudinal
      muscle contractility and decreased the K(H) to 2.2 pM (increased muscarinic
      receptor affinity), whereas preincubation with IFN-gamma increased the K(H) to
      0.4 muM (decreased muscarinic receptor affinity) and decreased longitudinal
      muscle contractility. Preincubation of LMMP with IL-13 decreased the K(H) to 0.2
      nM. Cytokines exert differential effects on the muscarinic receptor on intestinal
      longitudinal smooth muscle. These findings explain the basis for altered muscle
      contractility observed in Th1 and Th2 models of inflammation, as well as in the
      post-nematode-infected state.

PMID- 17431208
TI  - Recovery of cognitive function after surgery for aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Abnormalities in neurocognitive function are common after
      surgery for aneurysmal subarachnoid hemorrhage, even among patients with good
      functional outcomes. The time course of neurocognitive recovery, along with the
      long-term effects of mild intraoperative hypothermia (33 degrees C) and aneurysm
      location, is unknown. We determined these in a subset of subarachnoid hemorrhage
      patients enrolled in the Intraoperative Hypothermia for Aneurysm Surgery Trial
      (IHAST). METHODS: We performed a longitudinal, multicenter, prospective, blinded
      study of adult IHAST patients with a Glasgow Outcome Score=1 or 2 (independent
      function), 3 months postsurgery and a matched control group (n=45). Subjects were
      tested with a 5-test cognitive function battery and standard neurological
      evaluations at 3, 9 and 15 months postsurgery. The primary outcome measure was a
      composite score on cognitive test performance. RESULTS: There were 303 IHAST
      patients available for inclusion: 218 eligible, 185 enrolled (89 hypothermic, 96
      normothermic). Significant cognitive improvement was noted from 3 to 9 (P<0.001)
      and 3 to 15 (P<0.001) months in both hypothermic and normothermic groups, even
      after adjusting for practice effects observed in the control group. No
      significant change was identified between 9 and 15 months. Neither mild
      hypothermia nor aneurysm location (anterior communicating artery versus others)
      had a significant effect on recovery over time or frequency of cognitive
      impairment. Compared with control group, the frequency of cognitive impairment (Z
      score <-1.96) in all patients at 3, 9 and 15 months was 36%, 26% and 23%,
      respectively. CONCLUSIONS: In this population, cognitive improvement continued
      beyond 3 months, with a plateau between 9 and 15 months. This was not affected by
      the use of intraoperative hypothermia or anatomical location of aneurysm.

PMID- 17431213
TI  - Exendin-4, but not dipeptidyl peptidase IV inhibition, increases small intestinal
      mass in GK rats.
AB  - Long-term treatment with dipeptidyl peptidase IV inhibitors (DPPIV-I) or glucagon
      like peptide (GLP)-1 analogs may potentially affect intestinal growth by down- or
      upregulating the intestinotrophic hormone GLP-2. This study compared the
      intestinotrophic effects of 12-wk administration of vehicle, exendin-4 (Ex-4; 5
      nmol/kg bid sc), or DPPIV-I (NN-7201, 10 mg/kg qd orally) in GK rats. Some
      animals were observed additionally for 9 wk after the end of treatment. Both
      treatments lowered glycated hemoglobin A1c at wk 12 vs. control (Ex-4, -0.8%;
      DPPIV-I, -0.4%). Body weight was reduced by Ex-4 compared with control (361 +/- 4
      vs. 399 +/- 5 g; P < 0.001) because of reduced food intake, whereas neither
      parameter was affected by DPPIV-I. Linear bone growth was unaffected by either
      treatment. After treatment end, food intake in Ex-4 animals increased, and, by wk
      21, body weight was identical in all groups. The small intestine of Ex-4-treated
      animals was larger at wk 12 compared with control (length, 135.6 +/- 1.6 vs.
      124.5 +/- 2.3 cm, P < 0.001; absolute weight, 8.4 +/- 0.2 vs. 6.4 +/- 0.4 g, P <
      0.001), being most pronounced proximally, where the absolute cross-sectional area
      related to body weight increased by 24% because of increased mucosal thickness.
      These effects were reversible, and 9 wk after the end of treatment, no
      differences between Ex-4 and control were apparent. Plasma GLP-2 concentrations
      were unaltered by either treatment, and Ex-4 had no agonistic or antagonistic
      effects on the transfected GLP-2 receptor. DPPIV-I had no intestinal effects. In
      conclusion, the continued presence of Ex-4 is necessary to maintain weight loss
      in GK rats. Effective antihyperglycemic treatment with Ex-4 increases intestinal
      mass reversibly, whereas DPPIV-I lacks intestinal effects.

PMID- 17431214
TI  - Agonists of protease-activated receptors 1 and 2 stimulate electrolyte secretion
      from mouse gallbladder.
AB  - Cholecystitis is one of the most common gastrointestinal diseases. Inflammation
      induces the activation of proteases that can signal to cells by cleaving protease
      activated receptors (PARs) to induce hemostasis, inflammation, pain, and repair.
      However, the distribution of PARs in the gallbladder is unknown, and their
      effects on gallbladder function have not been fully investigated. We localized
      immunoreactive PAR(1) and PAR(2) to the epithelium, muscle, and serosa of mouse
      gallbladder. mRNA transcripts corresponding to PAR(1) and PAR(2), but not PAR(4),
      were detected by RT-PCR and sequencing. Addition of thrombin and a PAR(1)
      selective activating peptide (TFLLRN-NH(2)) to the serosal surface of mouse
      gallbladder mounted in an Ussing chamber stimulated an increase in short-circuit
      current in wild-type but not PAR(1) knockout mice. Similarly, serosally applied
      trypsin and PAR(2) activating peptide (SLIGRL-NH(2)) increased short-circuit
      current in wild-type but not PAR(2) knockout mice. Proteases and activating
      peptides strongly inhibited electrogenic responses to subsequent stimulation with
      the same agonist, indicating homologous desensitization. Removal of HCO(3)(-)
      ions from the serosal buffer reduced responses to thrombin and trypsin by >80%.
      Agonists of PAR(1) and PAR(2) increase intracellular Ca(2+) concentration in
      isolated and cultured gallbladder epithelial cells. The COX-2 inhibitor meloxicam
      and an inhibitor of CFTR prevented the stimulatory effect of PAR(1) but not
      PAR(2). Thus PAR(1) and PAR(2) are expressed in the epithelium of the mouse
      gallbladder, and serosally applied proteases cause a HCO(3)(-) secretion. The
      effects of PAR(1) but not PAR(2) depend on generation of prostaglandins and
      activation of CFTR. These mechanisms may markedly influence fluid and electrolyte
      secretion of the inflamed gallbladder when multiple proteases are generated.

PMID- 17431215
TI  - Eosinophilia is induced in the colon of Th2-sensitized mice upon exposure to
      locally expressed antigen.
AB  - Eosinophilic inflammation is a feature of a variety of gastrointestinal (GI)
      disorders including eosinophil-associated GI disorder, allergy, inflammatory
      bowel disease, and parasite infection. Elucidating the mechanisms of eosinophil
      infiltration into the GI tract is important to the understanding of multiple
      disease processes. We hypothesize that eosinophilia in the large intestine
      (colon) can be induced by an antigen in a host that is associated with Th2-skewed
      antigen-specific immune responses. To investigate the importance of antigenic
      triggering, we established polarized antigen-specific Th2 type responses in
      BALB/c mice, using ovalbumin in conjunction with aluminum hydroxide. Upon
      challenge at the colonic mucosa through transient (3-4 days) expression of the
      antigen gene encoded in an adenovirus vector, sensitized animals developed
      significant subepithelial colonic inflammation, characterized by marked
      eosinophilic infiltration, and the presence of enlarged and increased numbers of
      lymphoid follicles. The alterations peaked around day 5 and resolved over the
      next 5-10 days, and no epithelial cell damage was detected through the entire
      course. Administration of a control (empty) adenovirus vector did not lead to any
      pathological changes. These data suggest that colonic eosinophilia can be induced
      by exposure to an antigen associated with preexisting Th2-skewed responses. Thus
      the model established here may provide a useful tool to study GI and, in
      particular, colonic inflammation with respect to underlying mechanisms involved
      in the recruitment and the immediate function of eosinophils.

PMID- 17431216
TI  - Caspase-8-mediated apoptosis induced by oxidative stress is independent of the
      intrinsic pathway and dependent on cathepsins.
AB  - Cell-death programs executed in the pancreas under pathological conditions remain
      largely undetermined, although the severity of experimental pancreatitis has been
      found to depend on the ratio of apoptosis to necrosis. We have defined mechanisms
      by which apoptosis is induced in pancreatic acinar cells by the oxidant stressor
      menadione. Real-time monitoring of initiator caspase activity showed that caspase
      9 (66% of cells) and caspase-8 (15% of cells) were activated within 30 min of
      menadione administration, but no activation of caspase-2, -10, or -12 was
      detected. Interestingly, when caspase-9 activation was inhibited, activation of
      caspase-8 was increased. Half-maximum activation (t(0.5)) of caspase-9 occurred
      within approximately 2 min and was identified at or in close proximity to
      mitochondria, whereas t(0.5) for caspase-8 occurred within approximately 26 min
      of menadione application and was distributed homogeneously throughout cells.
      Caspase-9 but not caspase-8 activation was blocked completely by the calcium
      chelator BAPTA or bongkrekic acid, an inhibitor of the mitochondrial permeability
      transition pore. In contrast, caspase-8 but not caspase-9 activation was blocked
      by the destruction of lysosomes (preincubation with Gly-Phe beta-naphthylamide, a
      cathepsin C substrate), loss of lysosomal acidity (bafilomycin A1), or inhibition
      of cathepsin L or D. Using pepstatin A-BODIPY FL conjugate, we confirmed
      translocation of cathepsin D out of lysosomes in response to menadione. We
      conclude that the oxidative stressor menadione induces two independent apoptotic
      pathways within pancreatic acinar cells: the classical mitochondrial calcium
      dependent pathway that is initiated rapidly in the majority of cells, and a
      slower, caspase-8-mediated pathway that depends on the lysosomal activities of
      cathepsins and is used when the caspase-9 pathway is disabled.

PMID- 17431217
TI  - Differential regulation of cyclin D1 and cell death by bile acids in primary rat
      hepatocytes.
AB  - Ursodeoxycholic (UDCA) and tauroursodeoxycholic (TUDCA) acids modulate apoptosis
      and regulate cell-cycle effectors, including cyclin D1. In contrast, deoxycholic
      acid (DCA) induces cell death and cyclin D1. In this study, we explored the role
      of cyclin D1 in DCA-induced toxicity and further elucidated the antiapoptotic
      function of UDCA and TUDCA in primary rat hepatocytes. Cells were incubated with
      DCA and with or without UDCA or TUDCA for 8-30 h. In addition, hepatocytes were
      transfected with either an adenovirus expressing cyclin D1 or with a cyclin D1
      reporter plasmid with or without bile acids. Finally, cells were cotransfected
      with short interfering RNA targeting p53. Unlike DCA, both UDCA and TUDCA reduced
      cyclin D1 expression and transcriptional activation, confirming our previous DNA
      microarray data. Furthermore, UDCA and TUDCA prevented DCA-induced cyclin D1 and
      cell death. Cyclin D1 overexpression increased DCA-induced Bax translocation,
      cytochrome c release, and apoptosis. However, UDCA and TUDCA were less efficient
      at decreasing cyclin D1 levels as well as DCA-induced changes with
      overexpression. Finally, after p53 silencing, the effects of cyclin D1
      overexpression were almost completely abrogated, whereas UDCA and TUDCA
      cytoprotective potential was reestablished. In conclusion, cyclin D1 is a
      relevant player in modulating apoptosis by bile acids, in part through a p53
      dependent mechanism.

PMID- 17431218
TI  - Secretagogues differentially activate endoplasmic reticulum stress responses in
      pancreatic acinar cells.
AB  - Endoplasmic reticulum (ER) stress leads to the accumulation of misfolded proteins
      in the ER lumen and initiates the unfolded protein response (UPR). Components of
      the UPR are important in pancreatic development, and recent studies have
      indicated that the UPR is activated in the arginine model of acute pancreatitis.
      However, the effects of secretagogues on UPR components in the pancreas are
      unknown. The present study aimed to examine the effects of different types and
      concentrations of secretagogues on acinar cell function and specific components
      of the UPR. Rat pancreatic acini were stimulated with the CCK analogs CCK8 (10 pM
      10 nM) or JMV-180 (10 nM-10 microM) or with bombesin (1-100 nM). Components of
      the UPR, including chaperone BiP expression, PKR-like ER kinase (PERK)
      phosphorylation, X box-binding protein 1 (XBP1) splicing, and CCAAT/enhancer
      binding protein homologous protein (CHOP) expression, were measured, as were
      effects on amylase secretion and intracellular trypsin activation. CCK8 generated
      a biphasic secretion dose-response curve, and high concentrations increased
      intracellular active trypsin levels. In contrast, JMV-180 and bombesin secretion
      dose-response curves were monophasic, and high concentrations did not increase
      intracellular trypsin activity. All three secretagogues increased BiP levels and
      XBP1 splicing. However, only supraphysiological levels of CCK8 associated with
      inhibited amylase secretion and trypsin activation stimulated PERK
      phosphorylation and expression of CHOP. The effects of CCK8 on UPR components
      were rapid, occurring within 5-20 min. In conclusion, ER stress response
      mechanisms appear to be involved in both pancreatic physiology and
      pathophysiology, and future efforts should be directed at understanding the roles
      of these mechanisms in the pancreas.

PMID- 17431219
TI  - Ectopic expression of caveolin-1 restores physiological contractile response of
      aged colonic smooth muscle.
AB  - Reduced colonic motility has been observed in aged rats with a parallel reduction
      in acetylcholine (ACh)-induced myosin light chain (MLC(20)) phosphorylation.
      MLC(20) phosphorylation during smooth muscle contraction is maintained by a
      coordinated signal transduction cascade requiring both PKC-alpha and RhoA.
      Caveolae are membrane microdomains that permit rapid and efficient coordination
      of different signal transduction cascades leading to sustained smooth muscle
      contraction of the colon. Here, we show that normal physiological contraction can
      be reinstated in aged colonic smooth muscle cells (CSMCs) upon transfection with
      wild-type caveolin-1 through the activation of both the RhoA/Rho kinase and PKC
      pathways. Our data demonstrate that impaired contraction in aging is an outcome
      of altered membrane translocation of PKC-alpha and RhoA with a concomitant
      reduction in the association of these molecules with the caveolae-specific
      protein caveolin-1, resulting in a parallel decrease in the myosin phosphatase
      targeting subunit (MYPT) and CPI-17 phosphorylation. Decreased MYPT and CPI-17
      phosphorylation activates MLC phosphatase activity, resulting in MLC(20)
      dephosphorylation, which may be responsible for decreased colonic motility in
      aged rats. Importantly, transfection of CSMCs from aged rats with wild-type
      yellow fluorescent protein-caveolin-1 cDNA restored translocation of RhoA and PKC
      alpha and phosphorylation of MYPT, CPI-17, and MLC(20), thereby restoring the
      contractile response to levels comparable with young adult rats. Thus, we propose
      that caveolin-1 gene transfer may represent a promising therapeutic treatment to
      correct the age-related decline in colonic smooth muscle motility.

PMID- 17431220
TI  - Electrical parameters and ion species for active transport in human esophageal
      stratified squamous epithelium and Barrett's specialized columnar epithelium.
AB  - The human esophagus is lined by stratified squamous epithelium (ESSE), and in
      some subjects with reflux disease the distal esophagus becomes lined by Barrett's
      specialized columnar epithelium (BSCE). ESSE and BSCE differ both histologically
      and functionally, the latter evident by differences in their in vivo transmural
      electrical potential difference (PD), ESSE averaging -15 mV and BSCE being
      greater than -25 mV. In this report we examine the basis for this difference in
      PD. This is done by mounting endoscopic biopsies of ESSE from 25 subjects without
      esophageal disease and BSCE from 19 with Barrett's esophagus in mini-Ussing
      chambers for electrical recordings basally and after bathing solution ion
      replacement. The results show that the PD of human ESSE reflects a low level of
      active ion transport (5.1 +/- 0.8 muA/cm(2)) combined with a high level of tissue
      (electrical) resistance (344 +/- 34 Omega.cm(2)) and that of BSCE reflects a high
      level of active transport (43.6 +/- 11.6 muA/cm(2)) combined with a low level of
      resistance (69 +/- 8 Omega.cm(2)). Furthermore, active transport in ESSE was
      principally due to sodium absorption whereas in BSCE it was equally divided
      between sodium absorption and anion (chloride/bicarbonate) secretion, the latter
      through an apical membrane, 4-acetamido4'-isothiocyano-2,2'-stilbenedisulfonic
      acid-sensitive anion channel. As an anion-secreting tissue with bicarbonate
      secretory capacity more than fivefold greater than ESSE, BSCE is better suited
      than ESSE for defense of the esophagus against reflux disease.

PMID- 17431221
TI  - Gas exchange response to short-acting beta2-agonists in chronic obstructive
      pulmonary disease severe exacerbations.
AB  - RATIONALE: Short-acting beta(2)-agonists are one of the mainstays of
      bronchodilator strategy for exacerbations of chronic obstructive pulmonary
      disease (COPD). The assessment of pulmonary gas exchange after salbutamol in COPD
      severe exacerbations remains unknown. OBJECTIVES: We investigated whether the
      effects of nebulized salbutamol during COPD severe exacerbations are associated
      with further deterioration of pulmonary gas exchange. METHODS: We examined
      patients with severe COPD when hospitalized for exacerbation (n = 9), and while
      in stable convalescence. MEASUREMENTS AND MAIN RESULTS: We assessed spirometry,
      arterial blood gases, systemic hemodynamics, and V/Q relationships 30 and 90
      minutes after administration of 5.0 mg salbutamol. At exacerbation, compared with
      baseline, 30 minutes after salbutamol administration, cardiac output (Q)
      increased (from 6.5 +/- [SEM] 0.4 to 7.3 +/- 0.5 L . min(-1)) (p < 0.03) alone,
      without inducing changes in gas exchange indices. When in convalescence, compared
      with baseline, 30 minutes after salbutamol, there was an increase in Q (from 5.7
      +/- 0.5 to 7.0 +/- 0.6 L . min(-1)) and Vo(2) (from 211 +/- 12 to 232 +/- 11 ml .
      min(-1)) (p < 0.002 each), whereas Pa(O(2)) decreased (from 71 +/- 4 to 63 +/- 3
      mm Hg) and alveolar-arterial Po(2) difference increased due to increased
      perfusion of low-V/Q-ratio regions (from 4.5 +/- 2.6 to 9.6 +/- 4.1% of Q) (p <
      0.05); Sa(O(2)) (93 +/- 2%) and Pa(CO(2)) (43 +/- 2 mm Hg) remained unchanged.
      This deleterious gas exchange response persisted at 90 minutes. CONCLUSIONS: At
      exacerbation, salbutamol does not aggravate pulmonary gas exchange abnormalities.
      When in convalescence, however, baseline lung function improvement was associated
      with a detrimental gas exchange response to salbutamol, resulting in further V/Q
      imbalance and small decreases in Pa(O(2)) compounded by small increases in Q and
      Vo(2).

PMID- 17431222
TI  - Pulmonary lymphangioleiomyomatosis in a karyotypically normal man without
      tuberous sclerosis complex.
AB  - RATIONALE: The three previously reported cases of conclusively documented
      pulmonary lymphangioleiomyomatosis (LAM) in men were associated with definite or
      probable tuberous sclerosis complex (TSC). OBJECTIVES: To describe an unequivocal
      case of pulmonary LAM occurring in a man with no clinical or genotypic evidence
      of TSC. METHODS: At high-resolution computed tomography, a 37-year-old
      phenotypically and karyotypically normal man with left pneumothorax and massive
      pulmonary collapse had widespread thin-walled cysts throughout both lungs.
      Histological diagnosis of LAM was performed on biopsy material, and
      immunohistochemically confirmed with the HMB-45 monoclonal antibody. MEASUREMENTS
      AND MAIN RESULTS: Remarkably, the HMB-45-positive cells lining the cysts also
      showed strong reactivity for estrogen and progesterone receptor proteins. TSC was
      clinically excluded, and TSC1 and TSC2 germline mutations were not detected at
      DNA analysis. CONCLUSIONS: This article indicates that occurrence of LAM may be
      possible in a chromosomally normal man unaffected by TSC. On diagnostic grounds,
      the possibility of LAM should be borne in mind when diffuse cystic lung disease
      occurs in a man, even in the absence of signs of TSC.

PMID- 17431223
TI  - Bubble continuous positive airway pressure enhances lung volume and gas exchange
      in preterm lambs.
AB  - RATIONALE: The technique used to provide continuous positive airway pressure
      (CPAP) to the newborn may influence lung function and breathing efficiency.
      OBJECTIVES: To compare differences in gas exchange physiology and lung injury
      resulting from treatment of respiratory distress with either bubble or constant
      pressure CPAP and to determine if the applied flow influences short-term
      outcomes. METHODS: Lambs (133 d gestation; term is 150 d) born via cesarean
      section were weighed, intubated, and treated with CPAP for 3 hours. Two groups
      were treated with 8 L/minute applied flow using the bubble (n = 12) or the
      constant pressure (n = 12) technique. A third group (n = 10) received the bubble
      method with 12 L/minute bias flow. Measurements at study completion included
      arterial blood gases, oxygraphy, capnography, tidal flow, multiple breath
      washout, lung mechanics, static pressure-volume curves, and bronchoalveolar
      lavage fluid protein. MEASUREMENTS AND MAIN RESULTS: Birth weight and arterial
      gas variables at 15 minutes were comparable. Flow (8 or 12 L/min) did not
      influence the 3-hour outcomes in the bubble group. Bubble technique was
      associated with a higher pH, Pa(O2), oxygen uptake, and area under the flow
      volume curve, and a decreased alveolar protein, respiratory quotient, Pa(CO2),
      and ventilation inhomogeneity compared with the constant pressure group.
      CONCLUSIONS: Compared with constant pressure technique, bubble CPAP promotes
      enhanced airway patency during treatment of acute postnatal respiratory disease
      in preterm lambs and may offer protection against lung injury.

PMID- 17431224
TI  - Important roles for macrophage colony-stimulating factor, CC chemokine ligand 2,
      and mononuclear phagocytes in the pathogenesis of pulmonary fibrosis.
AB  - RATIONALE: An increase in the number of mononuclear phagocytes in lung biopsies
      from patients with idiopathic pulmonary fibrosis (IPF) worsens prognosis.
      Chemokines that recruit mononuclear phagocytes, such as CC chemokine ligand 2
      (CCL2), are elevated in bronchoalveolar lavage (BAL) fluid (BALF) from patients
      with IPF. However, little attention is given to the role of the mononuclear
      phagocyte survival and recruitment factor, macrophage colony-stimulating factor
      (M-CSF), in pulmonary fibrosis. OBJECTIVES: To investigate the role of
      mononuclear phagocytes and M-CSF in pulmonary fibrosis. METHODS: Wild-type, M-CSF
      /-, or CCL2-/- mice received intraperitoneal bleomycin. Lung inflammation and
      fibrosis were measured by immunohistochemistry, ELISA, collagen assay, BAL
      differentials, real-time polymerase chain reaction, and Western blot analysis.
      Human and mouse macrophages were stimulated with M-CSF for CCL2 expression. BALF
      from patients with IPF was examined for M-CSF and CCL2. MEASUREMENTS AND MAIN
      RESULTS: M-CSF-/- and CCL2-/- mice had less lung fibrosis, mononuclear phagocyte
      recruitment, collagen deposition, and connective tissue growth factor (CTGF)
      expression after bleomycin administration than wild-type littermates. Human and
      mouse macrophages stimulated with M-CSF had increased CCL2 production, and
      intratracheal administration of M-CSF in mice induced CCL2 production in BALF.
      Finally, BALF from patients with IPF contained significantly more M-CSF and CCL2
      than BALF from normal volunteers. Elevated levels of M-CSF were associated with
      elevated CCL2 in BALF and the diagnosis of IPF. CONCLUSIONS: These data suggest
      that M-CSF contributes to the pathogenesis of pulmonary fibrosis in mice and in
      patients with IPF through the involvement of mononuclear phagocytes and CCL2
      production.

PMID- 17431225
TI  - Local and circulating microchimerism is associated with hypersensitivity
      pneumonitis.
AB  - RATIONALE: Hypersensitivity pneumonitis (HP) is a lymphocytic alveolitis provoked
      by exposure to a variety of antigens. However, the disease occurs in only a
      subset of exposed individuals, suggesting that additional factors may be
      involved. Microchimerism has been implicated in the pathogenesis of autoimmune
      diseases, especially in those showing increased incidence after childbearing age.
      OBJECTIVES: To evaluate the presence of circulating and local microchimeric cells
      in female patients with HP. METHODS: Male microchimerism was examined in 103
      patients with HP, 30 with idiopathic pulmonary fibrosis (IPF), and 43 healthy
      women. All of them had given birth to at least one son, with no twin siblings,
      blood transfusions, or transplants. Microchimerism was examined by dot blot
      hybridization (peripheral blood), and by fluorescence in situ hybridization in
      bronchoalveolar lavage cells and lungs. MEASUREMENTS AND MAIN RESULTS: Blood
      microchimerism was found in 33% of the patients with HP in comparison with 10% in
      those with IPF (p = 0.019) and 16% in healthy women (p = 0.045). Patients with HP
      with microchimerism showed a significant reduction of diffusing capacity of
      carbon monoxide (Dl(CO); 53.5 +/- 11.9% vs. 65.2 +/- 19.7%; p = 0.02) compared
      with patients with HP without microchimerism. In bronchoalveolar lavage cells,
      microchimerism was detected in 9 of 14 patients with HP compared with 2 of 10
      patients with IPF (p = 0.047). Cell sorting revealed that microchimeric cells
      were either macrophages or CD4+ or CD8+ T cells. Male microchimeric cells were
      also found in the five HP lungs examined by fluorescence in situ hybridization.
      CONCLUSIONS: Our findings (1) demonstrate that patients with HP exhibit increased
      frequency of fetal microchimerism, (2) confirm the multilineage capacity of
      microchimeric cells, and (3) suggest that microchimeric cells may increase the
      severity of the disease.

PMID- 17431227
TI  - Diagnostic and therapeutic approach to nonsleepy apnea.
AB  - Epidemiological and observational studies suggest that sleep-disordered breathing
      is associated with the subsequent development of hypertension and ultimately with
      cardiovascular consequences. It may therefore be assumed that continuous positive
      airway pressure (CPAP) not only avoids sleep-related symptoms but could also
      mitigate cardiovascular consequences. Short-term studies have revealed a drop in
      blood pressure, especially in more severe, symptomatic cases of obstructive sleep
      apnea. Two recent studies have reported that nonsleepy obstructive sleep apnea is
      associated with an absence of reduced blood pressure after CPAP treatment. This
      suggests that this group of patients is less susceptible to the consequences of
      apneas, even those with mild-moderate hypertension or other cardiovascular
      disorders. However, in patients with severe cardiovascular disease or a higher
      number of obstructive events, CPAP treatment should be seriously considered.

PMID- 17431228
TI  - Novel perspectives for progesterone in hormone replacement therapy, with special
      reference to the nervous system.
AB  - The utility and safety of postmenopausal hormone replacement therapy has recently
      been put into question by large clinical trials. Their outcome has been
      extensively commented upon, but discussions have mainly been limited to the
      effects of estrogens. In fact, progestagens are generally only considered with
      respect to their usefulness in preventing estrogen stimulation of uterine
      hyperplasia and malignancy. In addition, various risks have been attributed to
      progestagens and their omission from hormone replacement therapy has been
      considered, but this may underestimate their potential benefits and therapeutic
      promises. A major reason for the controversial reputation of progestagens is that
      they are generally considered as a single class. Moreover, the term progesterone
      is often used as a generic one for the different types of both natural and
      synthetic progestagens. This is not appropriate because natural progesterone has
      properties very distinct from the synthetic progestins. Within the nervous
      system, the neuroprotective and promyelinating effects of progesterone are
      promising, not only for preventing but also for reversing age-dependent changes
      and dysfunctions. There is indeed strong evidence that the aging nervous system
      remains at least to some extent sensitive to these beneficial effects of
      progesterone. The actions of progesterone in peripheral target tissues including
      breast, blood vessels, and bones are less well understood, but there is evidence
      for the beneficial effects of progesterone. The variety of signaling mechanisms
      of progesterone offers exciting possibilities for the development of more
      selective, efficient, and safe progestagens. The recognition that progesterone is
      synthesized by neurons and glial cells requires a reevaluation of hormonal aging.

PMID- 17431229
TI  - Hepatic tumor necrosis factor signaling and nuclear factor-kappaB: effects on
      liver homeostasis and beyond.
AB  - The proinflammatory cytokine TNF has a pivotal role in liver pathophysiology
      because it holds the capacity to induce both hepatocyte cell death and hepatocyte
      proliferation. This dual effect of TNF on hepatocytes reflects its ability to
      induce both nuclear factor kappaB (NF-kappaB)-dependent gene expression and cell
      death. Multiple studies have demonstrated the crucial role of the transcription
      factor NF-kappaB in the decision between life and death of a hepatocyte. Massive
      hepatocyte apoptosis preceding embryonic lethality in NF-kappaB-deficient mice
      constituted the first indication of an essential antiapoptotic function of NF
      kappaB in the liver. Although many studies confirmed this crucial cytoprotective
      role of NF-kappaB in adult liver, a number of genetic studies recently obtained
      conflicting results on the exact role of NF-kappaB in different mouse models of
      TNF hepatotoxicity, demonstrating that caution should be taken when interpreting
      studies using different NF-kappaB-deficient mice in distinct models of liver
      injury. Recent reports showing a role for hepatic NF-kappaB activation in the
      proliferation of malignant cells during hepatocarcinogenesis, and in the
      progression of fatty liver diseases to insulin resistance and type 2 diabetes
      mellitus demonstrate that NF-kappaB can also have more detrimental effects in the
      liver. Moreover, its role in the development of the metabolic syndrome emphasizes
      that hepatic NF-kappaB activation might also have adverse effects on the
      endocrine system. Therefore, understanding the regulation of hepatic TNF
      signaling and NF-kappaB activation is of critical therapeutic importance. In this
      review, we summarize how studies on the role of NF-kappaB in different mouse
      models of liver pathologies have contributed to this understanding.

PMID- 17431230
TI  - Quality of drinking water.

PMID- 17431231
TI  - Composite and surrogate outcomes in randomised controlled trials.

PMID- 17431232
TI  - Inhaled nitric oxide for acute respiratory distress syndrome.

PMID- 17431233
TI  - Cytochrome P450 genotyping and antidepressants.

PMID- 17431234
TI  - Stockpiling smallpox virus.

PMID- 17431235
TI  - NHS chief must direct that time overseas is an asset.

PMID- 17431236
TI  - Bill aims to protect people at times of high risk.

PMID- 17431237
TI  - Article too strong? I think not.

PMID- 17431238
TI  - Editorial is unduly provocative.

PMID- 17431239
TI  - Understanding the history of medicine.

PMID- 17431226
TI  - Sex differences in severe pulmonary emphysema.
AB  - RATIONALE: Limited data on sex differences in advanced COPD are available.
      OBJECTIVES: To compare male and female emphysema patients with severe disease.
      METHODS: One thousand fifty-three patients (38.8% female) evaluated for lung
      volume reduction surgery as part of the National Emphysema Treatment Trial were
      analyzed. MEASUREMENTS AND MAIN RESULTS: Detailed clinical, physiological, and
      radiological assessment, including quantitation of emphysema severity and
      distribution from helical chest computed tomography, was completed. In a subgroup
      (n = 101), airway size and thickness was determined by histological analyses of
      resected tissue. Women were younger and exhibited a lower body mass index (BMI),
      shorter smoking history, less severe airflow obstruction, lower Dl(co) and
      arterial Po(2), higher arterial Pco(2), shorter six-minute walk distance, and
      lower maximal wattage during oxygen-supplemented cycle ergometry. For a given
      FEV(1)% predicted, age, number of pack-years, and proportion of emphysema, women
      experienced greater dyspnea, higher modified BODE, more depression, lower SF-36
      mental component score, and lower quality of well-being. Overall emphysema was
      less severe in women, with the difference from men most evident in the outer peel
      of the lung. Females had thicker small airway walls relative to luminal
      perimeters. CONCLUSIONS: In patients with severe COPD, women, relative to men,
      exhibit anatomically smaller airway lumens with disproportionately thicker airway
      walls, and emphysema that is less extensive and characterized by smaller hole
      size and less peripheral involvement.

PMID- 17431240
TI  - Academy of Royal Colleges spoke out in 2002.

PMID- 17431241
TI  - GMC to introduce "plea bargaining" for less serious misconduct cases.

PMID- 17431242
TI  - More than 90% of mothers with HIV fail to get help to stop their babies being
      born HIV positive.

PMID- 17431244
TI  - MPs back scientists' plea to be able to create hybrid embryos.

PMID- 17431246
TI  - Australia lags behind in attempts to improve health of indigenous people.

PMID- 17431247
TI  - HFEA wants greater use of single embryo transfers in assisted reproduction.

PMID- 17431248
TI  - Investigators will review conflicts of interest at NIH.

PMID- 17431249
TI  - BMA public health doctor is accused of stigmatising sex workers.

PMID- 17431251
TI  - More funding for maternity services is needed if women are to get choice over
      place of birth.

PMID- 17431252
TI  - Climate change is likely to affect the health of millions, report warns.

PMID- 17431254
TI  - Swapping scrubbing brushes for stethoscopes.

PMID- 17431259
TI  - European Working Time Directive: Battles in time.

PMID- 17431260
TI  - House of cards.

PMID- 17431261
TI  - Should the US and Russia destroy their stocks of smallpox virus?

PMID- 17431262
TI  - Should the US and Russia destroy their stocks of smallpox virus?

PMID- 17431263
TI  - The cancer diagnosis that has gripped America.

PMID- 17431264
TI  - Implications of shift work for junior doctors.

PMID- 17431266
TI  - Investigating suspected cerebral venous thrombosis.

PMID- 17431265
TI  - Post-traumatic stress disorder.

PMID- 17431267
TI  - Intensive care.

PMID- 17431268
TI  - Chronic obstructive pulmonary disease.

PMID- 17431276
TI  - Beyond HDL-cholesterol increase: phospholipid enrichment and shift from HDL3 to
      HDL2 in alcohol consumers.
AB  - The reduction of cardiovascular mortality associated with moderate alcohol
      consumption is chiefly thought to be mediated by an increase of high density
      lipoprotein cholesterol (HDL-CH). This study highlights additional qualitative
      changes of HDL that might augment this antiatherogenic effect. In 279 healthy
      men, alcohol and nutrient consumption were evaluated. Groups 1 (n=62), 2 (n=172),
      and 3 (n=45) comprised subjects with alcohol consumption of 0-5.0, 5.1-30.0, and
      30.1-75 g/day, respectively. Lipid analysis was performed in nonfractionated and
      fractionated plasma, including subfractions HDL(2a), HDL(2b), and HDL(3). No
      difference in LDL-cholesterol was observed. Compared with group 1, groups 2 and 3
      exhibited significant increases of HDL-CH (group 1, 44 +/- 10 mg/dl; group 2, 51
      +/- 11 mg/dl; group 3, 55 +/- 11 mg/dl; mean +/- SD, P<0.0005), accompanied by
      enhanced lipidation of HDL (increase of the HDL(2)-CH/HDL(3)-CH ratio). Moreover,
      phospholipid enrichment of HDL occurred in alcohol consumers, whereas the ratios
      between other HDL components remained constant. Multivariate analysis revealed
      alcohol to have the foremost statistical influence on changes of the HDL
      fraction, followed by body mass index and physical activity level. The increased
      lipidation of HDL found in alcohol consumers might augment the antiatherogenic
      effect of HDL-CH increase. In addition, the phospholipid enrichment of HDL might
      reduce the inflammatory response of atherogenesis.

PMID- 17431278
TI  - Stop TB: a long way to go, but new twists & turns in the science.

PMID- 17431277
TI  - Ultrasound use in trauma: the FAST exam.

PMID- 17431279
TI  - Association of infection with coronary artery disease.

PMID- 17431280
TI  - Understanding childhood depression.
AB  - Major depressive disorder in children is a severe and a chronically disabling
      disorder. This population appears to be a special group in terms of consequences
      of poor psychosocial and academic outcome and increased risk of substance abuse,
      and suicide. Studies have revealed several major findings in genetic, familial,
      psychological, and biological aspects of such depression, some of which have
      explored into the issue of its relationship with adult depression. Considerable
      advances have been made now in the area of childhood depression providing a
      better understanding of its nature. We review literature available on historical
      aspect, epidemiology, clinical characteristics, and aetiology of childhood
      depression.

PMID- 17431281
TI  - Association of common chronic infections with coronary artery disease in patients
      without any conventional risk factors.
AB  - BACKGROUND & OBJECTIVES: Report from the west suggest an association of
      infections and inflammation with atherosclerotic coronary artery disease (CAD).
      Entire microbial burden from several simultaneous chronic infections could be
      more important than a single infection in promoting atherosclerosis. No study has
      been done in Indian population, investigating the association of various chronic
      infections with CAD. We therefore evaluated the presence of markers of chronic
      infections in CAD patients having no conventional risk factors and healthy
      individuals in a tertiary care hospital in north India. METHODS: Seropositivity
      to IgG antibodies was investigated for Chlamydia pneumoniae, Mycoplasma
      pneumoniae, and Helicobacter pylori in 30 CAD patients with no conventional risk
      factors scheduled for coronary artery bypass surgery and in healthy blood donors.
      Periodontal pathogens were isolated by aerobic and anaerobic culture. RESULTS:
      All patients except one were < 55 yr of age and six were younger than 40 yr.
      Seropositivity to C. pneumoniae was significantly higher in CAD patients than
      healthy controls (63.3 vs. 23.3%, P<0.01). Combined seropositivity to both C.
      pneumoniae and M. pneumoniae was significantly higher in CAD patients with
      myocardial infarction (MI) than those without MI (61.5 vs. 11.8%, P<0.05).
      Aerobic and anaerobic cultures for the isolation of periodontal pathogens were
      positive in seven patients and five healthy blood donors. INTERPRETATION &
      CONCLUSION: C. pneumoniae seropositivity was significantly higher (P<0.001) in
      CAD patients without any of the conventional risk factors for CAD. Combined
      seropositivity to C. pneumoniae and M. pneumoniae was significantly higher
      (P<0.05) in CAD patients with MI than in those without MI. Possibly CAD in young
      is not (or less) governed by conventional risk factors, and infectious agents can
      be potential risk factors for the development of atherosclerosis and CAD in this
      subset of patients.

PMID- 17431282
TI  - Clinical utility of serum human epidermal receptor-2/neu detection in breast
      cancer patients.
AB  - BACKGROUND & OBJECTIVE: In breast cancer, the HER-2/neu gene is amplified in 20
      30 per cent of cases. The mechanism by which the amplification/overexpression
      occurs is not known. Elevated serum HER-2/neu levels have been shown to be
      associated with a poor clinical prognosis and decreased survival in early stage
      breast cancer patients, and thus might help in management of the disease. The
      present study was therefore to estimate the serum HER-2/neu levels in breast
      cancer patients and associate with other prognostic factors. METHODS: Serum HER
      2/neu levels were studied in 207 patients with cancer breast, 15 benign breast
      diseases (BBD) and 175 age-matched healthy controls. Patients' age, menopausal
      status, node and hormone receptor status were compared with serum HER-2/neu
      levels. RESULTS: Serum HER-2/neu overexpression was associated with age, disease
      stage and positive nodal status but not with menopausal status. Serum HER-2/neu
      levels were negatively related with hormone receptor positivity. INTERPRETATION &
      CONCLUSION: HER-2/neu serum test could be done more frequently in women with
      breast cancer irrespective of the hormone receptor status, to suggest
      modifications in systemic adjuvant therapy, including possibly the use of
      Herceptin.

PMID- 17431283
TI  - Oxidative stress in sepsis in children.
AB  - BACKGROUND & OBJECTIVE: Information on oxidative damage during sepsis in children
      is not available, we undertook this study to assess the levels of certain
      antioxidants in blood of children with sepsis. METHODS: Study group had 38
      children with sepsis (<5 yr) and 39 age-and sex-matched controls admitted to a
      tertiary care hospital. Red cell glutathione (GSH), superoxide dismutase (SOD)
      and thiobarbituric acid reactive substance (TBARS) and plasma vitamin C were
      estimated by standard techniques. RESULTS: There was no significant change in
      erythrocyte GSH, SOD and TBARS levels in sepsis when compared to controls. This
      may be due to the adaptive response of the body to combat the oxidative stress.
      However, plasma vitamin C levels were significantly reduced in patients aged one
      year one month to five years which may be due to active phagocytosis and due to
      its role as a free radical scavenger. INTERPRETATION & CONCLUSION: Our findings
      show that children affected by sepsis probably adapt to the free radical toxicity
      induced by this condition. Further studies need to be done on a larger sample to
      confirm the findings.

PMID- 17431284
TI  - Promotion of cutaneous wound healing by famotidine in Wistar rats.
AB  - BACKGROUND & OBJECTIVE: Drugs like famotidine, omeprazole and sucralfate which
      have been reported to promote the healing of gastric ulcers, may have the same
      effect on cutaneous wounds. Due to paucity of information in this regard, the
      present study was planned to investigate the effect of these drugs on resutured
      incision, excision and dead space wounds in Wistar rats. METHODS: Resutured
      incision, excision and dead space wounds were inflicted under light ether
      anaesthesia aseptically. Control animals received vehicle and other groups
      received famotidine, omeprazole and sucralfate orally for a period of 10 days in
      the incision and dead space wounds, whereas in excision wounds till complete
      closure. On the 11th day after estimating breaking strength of the resutured
      incision wounds, animals were sacrificed and granulation tissue removed from dead
      space wounds to estimate the breaking strength and hydroxyproline content.
      Quantification of granulation tissue and histological studies were also carried
      out. Wound closure rate, epithelization time and scar features were studied in
      the excision wound models from the day of famotidine till complete closure of the
      wound. RESULTS: Only famotidine significantly promoted the healing process in all
      the three wound models studied. Histopathological studies revealed increased
      collagen content and granulation tissue in famotidine treated group compared to
      control. INTERPRETATION & CONCLUSION: In all the three wound models studied
      famotidine promoted wound healing whereas omeprazole and sucralfate did not do
      so. The pro healing effect of famotidine needs to be explored clinically.

PMID- 17431285
TI  - Rapid identification of mycobacteria by gene amplification restriction analysis
      technique targeting 16S-23S ribosomal RNA internal transcribed spacer & flanking
      region.
AB  - BACKGROUND & OBJECTIVE: Conventional identification of a clinical isolate of
      mycobacteria primarily based on culture characteristics and biochemical tests
      needs several weeks and may remain inconclusive. This study was undertaken to
      develop a new rapid method to identify the mycobacterial isolates at species
      level by gene amplification restriction analysis using primers encoding 16S-23S
      rRNA internal transcribed spacer (ITS) region and flanking parts of the 16S as
      well as 23S rRNA gene. METHODS: This system is based on the amplification of
      approximately 1.8 kb fragment encoding 16S-23S rRNA spacer region and flanking
      parts of the 16S as well as 23S rRNA gene. This assay was applied on 13 reference
      strains and 480 clinical isolates of mycobacteria to validate the technique.
      Restriction was carried out with three restriction endonucleases Hha I, Hinf I
      and Rsa I. RESULTS: Distinct gene amplification restriction analysis patterns
      were obtained by restriction of amplicons with three distinct restriction
      endonucleases (Hha I, Hinf I and Rsa I) which could differentiate various
      mycobacterial species. INTERPRETATION & CONCLUSION: Restriction patterns with the
      enzymes used in this study could clearly distinguish Mycobacterium tuberculosis
      complex from other non chromogenic clinically important species M. avium and M.
      intracellulare. Results indicated this assay to be a simple, rapid and
      reproducible method to identify clinically relevant mycobacteria.

PMID- 17431286
TI  - Persistently high HIV seroprevalence among adult tuberculosis patients at a
      tertiary care centre in Delhi.
AB  - BACKGROUND & OBJECTIVE: This study was designed to estimate HIV seroprevalence
      among tuberculosis patients presenting to tertiary care centre in Delhi. METHODS:
      Cross-sectional prevalence study among all patients presenting to the inpatient
      and outpatient departments of All India Institute of Medical Sciences (AIIMS),
      New Delhi, and receiving anti-tuberculosis treatment from May 2003 to April 2005.
      RESULTS: Of the 448 patients who presented to the TB clinic during the study
      period, 23 (5.1%) were previously tested HIV-positive. An additional 21 patients
      (4.6%) refused testing, and 30 (6.7%) were lost to follow up. Of the remaining
      374 patients who consented to testing, 31 (8.3%) were found to be HIV-positive.
      Risk factors for HIV seropositivity included high-risk sexual behaviours (48% in
      HIV-TB co-infected vs. 6% in TB infected patients, P<0.001) and history of blood
      transfusion (23% vs. 5%; P=0.002). INTERPRETATION & CONCLUSION: Previous studies
      from the same hospital published in 2000 and 2003 reported HIV seroprevalence
      among TB patients to be 0.4 and 9.4 per cent respectively. The current study
      documents a persistently high seropositivity among TB patients. These results
      emphasize the acute need for improved detection and treatment for HIV among TB
      patients in northern India.

PMID- 17431287
TI  - Prevalence of bacterial vaginosis among women in Delhi, India.
AB  - BACKGROUND & OBJECTIVE: Bacterial vaginosis is the most common cause of vaginal
      discharge among women in reproductive age. Surveillance studies on bacterial
      vaginosis are mostly based on specialist clinic settings. As few population-based
      prevalence surveys of bacterial vaginosis have been conducted, we studied the
      prevalence of bacterial vaginosis in the urban and rural communities in Delhi,
      and to associate the presence of bacterial vaginosis with demographic profile,
      risk factors and presence of other reproductive tract infections (RTIs)/ sexually
      transmitted infections (STIs). METHODS: Vaginal specimens for Gram-stain
      evaluation of vaginal flora for diagnosis of bacterial vaginosis and culture of
      Trichomonas vaginalis and Candida spp, blood samples for HIV and syphilis
      serology, and urine for detection of Neisseria gonorrhoeae and Chlamydia
      trachomatis were collected from women (15-49 yr) from rural and urban areas.
      Information on demographic characteristics, risk factors and clinical symptoms
      was obtained. RESULTS: Bacterial vaginosis was diagnosed in 70 (32.8%) subjects.
      A high percentage though asymptomatic (31.2%) were found to have bacterial
      vaginosis. Highest prevalence was seen in urban slum (38.6%) followed by rural
      (28.8%) and urban middle class community (25.4%). All women with vaginal
      trichomoniasis were found to have bacterial vaginosis while 50 per cent of
      subjects having syphilis also had bacterial vaginosis.. INTERPRETATION &
      CONCLUSION: The study showed high prevalence of bacterial vaginosis. The
      asymptomatic women having bacterial vaginosis are less likely to seek treatment
      for the morbidity and thus are more likely to acquire other STIs. Women attending
      various healthcare facilities should be screened and treated for bacterial
      vaginosis to reduce the risk of acquisition of other STIs.

PMID- 17431288
TI  - Occurrence of TEM & SHV gene in extended spectrum beta-lactamases (ESBLs)
      producing Klebsiella sp. isolated from a tertiary care hospital.
AB  - BACKGROUND & OBJECTIVE: Extended-spectrum beta-lactamases (ESBLs) are rapidly
      evolving group of beta-lactamase enzymes produced by the Gram negative bacteria.
      These enzymes have been derived from TEM and SHV genes by mutations and have been
      well described in Klebsiella pneumoniae. Information on molecular types of ESBL
      positive Klebsiella sp. is lacking from India. We therefore undertook this study
      to look for the TEM and SHV genes in ESBL positive Klebsiella sp. isolated from
      the patients admitted to a tertiary care hospital in north India. METHODS: A
      total of 204 multidrug-resistant isolates of Klebsiellae obtained from clinical
      samples; blood (n=108), urine (n=15), pus (n=2) and sputum (n=79) were obtained
      and screened for resistance to 3rd generation cephalosporins (3GC). The ESBL
      status was determined by double disk diffusion test (DDDT) and further by ESBL E
      test. Multiplex PCR specific for TEM and SHV genes was performed to distinguish
      four different genotypes: TEM-positive, SHV-positive, TEM- and SHV-positive and
      non-TEM non-SHV ESBL types. RESULTS: Eighty six per cent (175 of 204) of the
      isolates were found to be resistant to at least one of the 3GCs, of which 97.1
      per cent (170) of Klebsiella sp. isolates were confirmed to be positive for ESBL.
      Of these 170 isolates, 95 were randomly selected for PCR of TEM and SHV genes.
      Isolates having both TEM and SHV genes were common (67.3%) whereas only 20 per
      cent isolates possessed TEM gene and 8.4 per cent SHV gene alone. INTERPRETATION
      & CONCLUSION: Our findings showed that the majority of the ESBL positive clinical
      isolates of Klebsiella sp. carried both TEM and SHV genes followed by TEM alone.
      Such studies need to be done in various geographical regions of the country to
      know about the prevalent genotypes for better management of infection.

PMID- 17431289
TI  - A focal outbreak of dengue fever in a rural area of Tamil Nadu.

PMID- 17431290
TI  - Exercise testing in miliary tuberculosis--some facts.

PMID- 17431291
TI  - Beta cell protection & metabolic syndrome.

PMID- 17431292
TI  - Upsetting the balance.

PMID- 17431293
TI  - Dynamic texture recognition using local binary patterns with an application to
      facial expressions.
AB  - Dynamic texture (DT) is an extension of texture to the temporal domain.
      Description and recognition of DTs have attracted growing attention. In this
      paper, a novel approach for recognizing DTs is proposed and its simplifications
      and extensions to facial image analysis are also considered. First, the textures
      are modeled with volume local binary patterns (VLBP), which are an extension of
      the LBP operator widely used in ordinary texture analysis, combining motion and
      appearance. To make the approach computationally simple and easy to extend, only
      the co-occurrences of the local binary patterns on three orthogonal planes (LBP
      TOP) are then considered. A block-based method is also proposed to deal with
      specific dynamic events such as facial expressions in which local information and
      its spatial locations should also be taken into account. In experiments with two
      DT databases, DynTex and Massachusetts Institute of Technology (MIT), both the
      VLBP and LBP-TOP clearly outperformed the earlier approaches. The proposed block
      based method was evaluated with the Cohn-Kanade facial expression database with
      excellent results. The advantages of our approach include local processing,
      robustness to monotonic gray-scale changes, and simple computation.

PMID- 17431294
TI  - Toward objective evaluation of image segmentation algorithms.
AB  - Unsupervised image segmentation is an important component in many image
      understanding algorithms and practical vision systems. However, evaluation of
      segmentation algorithms thus far has been largely subjective, leaving a system
      designer to judge the effectiveness of a technique based only on intuition and
      results in the form of a few example segmented images. This is largely due to
      image segmentation being an ill-defined problem-there is no unique ground-truth
      segmentation of an image against which the output of an algorithm may be
      compared. This paper demonstrates how a recently proposed measure of similarity,
      the Normalized Probabilistic Rand (NPR) index, can be used to perform a
      quantitative comparison between image segmentation algorithms using a hand
      labeled set of ground-truth segmentations. We show that the measure allows
      principled comparisons between segmentations created by different algorithms, as
      well as segmentations on different images. We outline a procedure for algorithm
      evaluation through an example evaluation of some familiar algorithms-the mean
      shift-based algorithm, an efficient graph-based segmentation algorithm, a hybrid
      algorithm that combines the strengths of both methods, and expectation
      maximization. Results are presented on the 300 images in the publicly available
      Berkeley Segmentation Data Set.

PMID- 17431295
TI  - Curve/surface representation and evolution using vector level sets with
      application to the shape-based segmentation problem.
AB  - In this paper, we revisit the implicit front representation and evolution using
      the vector level set function (VLSF) proposed in [1]. Unlike conventional scalar
      level sets, this function is designed to have a vector form. The distance from
      any point to the nearest point on the front has components (projections) in the
      coordinate directions included in the vector function. This kind of
      representation is used to evolve closed planar curves and 3D surfaces as well.
      Maintaining the VLSF property as the distance projections through evolution will
      be considered together with a detailed derivation of the vector partial
      differential equation (PDE) for such evolution. A shape-based segmentation
      framework will be demonstrated as an application of the given implicit
      representation. The proposed level set function system will be used to represent
      shapes to give a dissimilarity measure in a variational object registration
      process. This kind of formulation permits us to better control the process of
      shape registration, which is an important part in the shape-based segmentation
      framework. The method depends on a set of training shapes used to build a
      parametric shape model. The color is taken into consideration besides the shape
      prior information. The shape model is fitted to the image volume by registration
      through an energy minimization problem. The approach overcomes the conventional
      methods problems like point correspondences and weighing coefficients tuning of
      the evolution (PDEs). It is also suitable for multidimensional data and
      computationally efficient. Results in 2D and 3D of real and synthetic data will
      demonstrate the efficiency of the framework.

PMID- 17431296
TI  - Matching by linear programming and successive convexification.
AB  - We present a novel convex programming scheme to solve matching problems, focusing
      on the challenging problem of matching in a large search range and with cluttered
      background. Matching is formulated as metric labeling with L1 regularization
      terms, for which we propose a novel linear programming relaxation method and an
      efficient successive convexification implementation. The unique feature of the
      proposed relaxation scheme is that a much smaller set of basis labels is used to
      represent the original label space. This greatly reduces the size of the
      searching space. A successive convexification scheme solves the labeling problem
      in a coarse to fine manner. Importantly, the original cost function is
      reconvexified at each stage, in the new focus region only, and the focus region
      is updated so as to refine the searching result. This makes the method well
      suited for large label set matching. Experiments demonstrate successful
      applications of the proposed matching scheme in object detection, motion
      estimation, and tracking.

PMID- 17431297
TI  - Model-based tracking by classification in a tiny discrete pose space.
AB  - A method is presented for tracking 3D objects as they transform rigidly in space
      within a sparse range image sequence. The method operates in discrete space and
      exploits the coherence across image frames that results from the relationship
      between known bounds on the object's velocity and the sensor frame rate. These
      motion bounds allow the interframe transformation space to be reduced to a
      reasonable and indeed tiny size, comprising only tens or hundreds of possible
      states. The tracking problem is in this way cast into a classification framework,
      effectively trading off localization precision for runtime efficiency and
      robustness. The method has been implemented and tested extensively on a variety
      of freeform objects within a sparse range data stream comprising only a few
      hundred points per image. It has been shown to compare favorably against
      continuous domain Iterative Closest Point (ICP) tracking methods, performing both
      more efficiently and more robustly. A hybrid method has also been implemented
      that executes a small number of ICP iterations following the initial discrete
      classification phase. This hybrid method is both more efficient than the ICP
      alone and more robust than either the discrete classification method or the ICP
      separately.

PMID- 17431298
TI  - Mask-based second-generation connectivity and attribute filters.
AB  - Connected filters are edge-preserving morphological operators, which rely on a
      notion of connectivity. This is usually the standard 4 and 8-connectivity, which
      is often too rigid since it cannot model generalized groupings such as object
      clusters or partitions. In the set-theoretical framework of connectivity, these
      groupings are modeled by the more general second-generation connectivity. In this
      paper, we present both an extension of this theory, and provide an efficient
      algorithm based on the Max-Tree to compute attribute filters based on these
      connectivities. We first look into the drawbacks of the existing framework that
      separates clustering and partitioning and is directly dependent on the properties
      of a preselected operator. We then propose a new type of second-generation
      connectivity termed mask-based connectivity which eliminates all previous
      dependencies and extends the ways the image domain can be connected. A previously
      developed Dual-Input Max-Tree algorithm for area openings is adapted for the
      wider class of attribute filters on images characterized by second-generation
      connectivity. CPU-times for the new algorithm are comparable to the original
      algorithm, typically deviating less than 10 percent either way.

PMID- 17431299
TI  - Discriminative learning and recognition of image set classes using canonical
      correlations.
AB  - We address the problem of comparing sets of images for object recognition, where
      the sets may represent variations in an object's appearance due to changing
      camera pose and lighting conditions. Canonical Correlations (also known as
      principal or canonical angles), which can be thought of as the angles between two
      d-dimensional subspaces, have recently attracted attention for image set
      matching. Canonical correlations offer many benefits in accuracy, efficiency, and
      robustness compared to the two main classical methods: parametric distribution
      based and nonparametric sample-based matching of sets. Here, this is first
      demonstrated experimentally for reasonably sized data sets using existing methods
      exploiting canonical correlations. Motivated by their proven effectiveness, a
      novel discriminative learning method over sets is proposed for set
      classification. Specifically, inspired by classical Linear Discriminant Analysis
      (LDA), we develop a linear discriminant function that maximizes the canonical
      correlations of within-class sets and minimizes the canonical correlations of
      between-class sets. Image sets transformed by the discriminant function are then
      compared by the canonical correlations. Classical orthogonal subspace method
      (OSM) is also investigated for the similar purpose and compared with the proposed
      method. The proposed method is evaluated on various object recognition problems
      using face image sets with arbitrary motion captured under different
      illuminations and image sets of 500 general objects taken at different views. The
      method is also applied to object category recognition using ETH-80 database. The
      proposed method is shown to outperform the state-of-the-art methods in terms of
      accuracy and efficiency.

PMID- 17431300
TI  - Recognition of pornographic web pages by classifying texts and images.
AB  - With the rapid development of the World Wide Web, people benefit more and more
      from the sharing of information. However, Web pages with obscene, harmful, or
      illegal content can be easily accessed. It is important to recognize such
      unsuitable, offensive, or pornographic Web pages. In this paper, a novel
      framework for recognizing pornographic Web pages is described. A C4.5 decision
      tree is used to divide Web pages, according to content representations, into
      continuous text pages, discrete text pages, and image pages. These three
      categories of Web pages are handled, respectively, by a continuous text
      classifier, a discrete text classifier, and an algorithm that fuses the results
      from the image classifier and the discrete text classifier. In the continuous
      text classifier, statistical and semantic features are used to recognize
      pornographic texts. In the discrete text classifier, the naive Bayes rule is used
      to calculate the probability that a discrete text is pornographic. In the image
      classifier, the object's contour-based features are extracted to recognize
      pornographic images. In the text and image fusion algorithm, the Bayes theory is
      used to combine the recognition results from images and texts. Experimental
      results demonstrate that the continuous text classifier outperforms the
      traditional keyword-statistics-based classifier, the contour-based image
      classifier outperforms the traditional skin-region-based image classifier, the
      results obtained by our fusion algorithm outperform those by either of the
      individual classifiers, and our framework can be adapted to different categories
      of Web pages.

PMID- 17431301
TI  - Iterative RELIEF for feature weighting: algorithms, theories, and applications.
AB  - RELIEF is considered one of the most successful algorithms for assessing the
      quality of features. In this paper, we propose a set of new feature weighting
      algorithms that perform significantly better than RELIEF, without introducing a
      large increase in computational complexity. Our work starts from a mathematical
      interpretation of the seemingly heuristic RELIEF algorithm as an online method
      solving a convex optimization problem with a margin-based objective function.
      This interpretation explains the success of RELIEF in real application and
      enables us to identify and address its following weaknesses. RELIEF makes an
      implicit assumption that the nearest neighbors found in the original feature
      space are the ones in the weighted space and RELIEF lacks a mechanism to deal
      with outlier data. We propose an iterative RELIEF (I-RELIEF) algorithm to
      alleviate the deficiencies of RELIEF by exploring the framework of the
      Expectation-Maximization algorithm. We extend I-RELIEF to multiclass settings by
      using a new multiclass margin definition. To reduce computational costs, an
      online learning algorithm is also developed. Convergence analysis of the proposed
      algorithms is presented. The results of large-scale experiments on the UCI and
      microarray data sets are reported, which demonstrate the effectiveness of the
      proposed algorithms, and verify the presented theoretical results.

PMID- 17431302
TI  - MonoSLAM: real-time single camera SLAM.
AB  - We present a real-time algorithm which can recover the 3D trajectory of a
      monocular camera, moving rapidly through a previously unknown scene. Our system,
      which we dub MonoSLAM, is the first successful application of the SLAM
      methodology from mobile robotics to the "pure vision" domain of a single
      uncontrolled camera, achieving real time but drift-free performance inaccessible
      to Structure from Motion approaches. The core of the approach is the online
      creation of a sparse but persistent map of natural landmarks within a
      probabilistic framework. Our key novel contributions include an active approach
      to mapping and measurement, the use of a general motion model for smooth camera
      movement, and solutions for monocular feature initialization and feature
      orientation estimation. Together, these add up to an extremely efficient and
      robust algorithm which runs at 30 Hz with standard PC and camera hardware. This
      work extends the range of robotic systems in which SLAM can be usefully applied,
      but also opens up new areas. We present applications of MonoSLAM to real-time 3D
      localization and mapping for a high-performance full-size humanoid robot and live
      augmented reality with a hand-held camera.

PMID- 17431303
TI  - Stereo correspondence with occlusion handling in a symmetric patch-based graph
      cuts model.
AB  - A novel patch-based correspondence model is presented in this paper. Many segment
      based correspondence approaches have been proposed in recent years. Untextured
      pixels and boundaries of discontinuities are imposed with hard constraints by the
      discontinuity assumption that large disparity variation only happens at the
      boundaries of segments in the above approaches. Significant improvements on
      performance of untextured and discontinuity area have been reported. But, the
      performance near occlusion is not satisfactory because a segmented region in one
      image may be only partially visible in the other one. To solve this problem, we
      utilize the observation that the shared edge of a visible area and an occluded
      area corresponds to the discontinuity in the other image. So, the proposed model
      conducts color segmentation on both images first and then a segment in one image
      is further cut into smaller patches corresponding to the boundaries of segments
      in the other when it is assigned with a disparity. Different visibility of
      patches in one segment is allowed. The uniqueness constraint in a segment level
      is used to compute the occlusions. An energy minimization framework using graph
      cuts is proposed to find a global optimal configuration including both
      disparities and occlusions. Besides, some measurements are taken to make our
      segment-based algorithm suffer less from violation of the discontinuity
      assumption. Experimental results have shown superior performance of the proposed
      approach, especially on occlusions, untextured areas, and near discontinuities.

PMID- 17431304
TI  - Focus area extraction by blind deconvolution for defining regions of interest.
AB  - We present an automatic focus area estimation method, working with a single image
      without a priori information about the image, the camera, or the scene. It
      produces relative focus maps by localized blind deconvolution and a new residual
      error-based classification. Evaluation and comparison is performed and
      applicability is shown through image indexing.

PMID- 17431305
TI  - The Bayes decision rule induced similarity measures.
AB  - This paper first shows that the popular whitened cosine similarity measure is
      related to the Bayes decision rule under specific assumptions and then presents
      two new similarity measures: the PRM Whitened Cosine (PWC) similarity measure and
      the Within-Class Whitened Cosine (WWC) similarity measure. Experiments on face
      recognition using the Face Recognition Grand Challenge (FRGC) version 2 database
      show the effectiveness of the new measures.

PMID- 17431306
TI  - A normalized Levenshtein distance metric.
AB  - Although a number of normalized edit distances presented so far may offer good
      performance in some applications, none of them can be regarded as a genuine
      metric between strings because they do not satisfy the triangle inequality. Given
      two strings X and Y over a finite alphabet, this paper defines a new normalized
      edit distance between X and Y as a simple function of their lengths (|X| and |Y|)
      and the Generalized Levenshtein Distance (GLD) between them. The new distance can
      be easily computed through GLD with a complexity of O(|X|.|Y|) and it is a metric
      valued in [0, 1] under the condition that the weight function is a metric over
      the set of elementary edit operations with all costs of insertions/deletions
      having the same weight. Experiments using the AESA algorithm in handwritten digit
      recognition show that the new distance can generally provide similar results to
      some other normalized edit distances and may perform slightly better if the
      triangle inequality is violated in a particular data set.

PMID- 17431307
TI  - Space-time adaptation for patch-based image sequence restoration.
AB  - We present a novel space-time patch-based method for image sequence restoration.
      We propose an adaptive statistical estimation framework based on the local
      analysis of the bias-variance trade-off. At each pixel, the space-time
      neighborhood is adapted to improve the performance of the proposed patch-based
      estimator. The proposed method is unsupervised and requires no motion estimation.
      Nevertheless, it can also be combined with motion estimation to cope with very
      large displacements due to camera motion. Experiments show that this method is
      able to drastically improve the quality of highly corrupted image sequences.
      Quantitative evaluations on standard artificially noise-corrupted image sequences
      demonstrate that our method outperforms other recent competitive methods. We also
      report convincing results on real noisy image sequences.

PMID- 17431308
TI  - Toxicity and carcinogenicity mechanisms of fibrous antigorite.
AB  - We studied the effects of fibrous antigorite on mesothelial MeT-5A and monocyte
      macrophage J774 cell lines to further understand cellular mechanisms induced by
      asbestos fibers leading to lung damage and cancer. Antigorite is a mineral with
      asbestiform properties, which tends to associate with chrysotile or tremolite,
      and frequently occurs as the predominant mineral in the veins of several
      serpentinite rocks found abundantly in the Western Alps. Particles containing
      antigorite are more abundant in the breathing air of this region than those
      typically found in urban ambient air. Exposure of MeT-5A and J774 cells to
      fibrous antigorite at concentrations of 5-100 microg/ml for 72 hr induced dose
      dependent cytotoxicity. Antigorite also stimulated the ROS production, induced
      the generation of nitrite and PGE2. MeT-5A cells were more sensitive to
      antigorite than J774 cells. The results of this study revealed that the fibrous
      antigorite stimulates cyclooxygenase and formation of hydroxyl and nitric oxide
      radicals. These changes represent early cellular responses to antigorite fibers,
      which lead to a host of pathological and neoplastic conditions because free
      radicals and PGE2 play important roles as mediators of tumor pathogenesis.
      Understanding the mechanisms of the cellular responses to antigorite and other
      asbestos particles should be helpful in designing rational prevention and
      treatment approaches.

PMID- 17431309
TI  - Induction of cell death, DNA strand breaks, and cell cycle arrest in DU145 human
      prostate carcinoma cell line by benzo[a]pyrene and benzo[a]pyrene-7,8-diol-9,10
      epoxide.
AB  - Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon, is a major
      environmental pollutant. In this study, the effects of this carcinogen/mutagen
      and one of its metabolites, benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE), on human
      prostate carcinoma cell line DU145, were examined. Cell viability, DNA damage,
      and cell cycle progression were evaluated as toxic end-points. We have shown that
      B[a]P and BPDE inhibited cell viability following 48 hr of exposure. Furthermore,
      comet assay analyses revealed that both B[a]P and BPDE induced DNA strand breaks
      in a concentration-dependent fashion. Flow cytometric analyses showed that about
      70% of DU145 cells were arrested by B[a]P at the G1 phase, while about 76% were
      arrested at G1 phase by BPDE. These data reveal that B[a]P and BPDE are cytotoxic
      and genotoxic to DU145 prostate cancer cells.

PMID- 17431310
TI  - Human arsenic poisoning issues in central-east Indian locations: biomarkers and
      biochemical monitoring.
AB  - The study reports the use of three biomarkers i.e. total arsenic in hair and
      nails, total arsenic in blood, and total arsenic in urine to identify or quantify
      arsenic exposure and concomitant health effects. The main source of arsenic was
      inorganic exposure through drinking water. The arsenic levels and the health
      effects were analyzed closely in a family having maximum symptoms of arsenic.
      Based on the result of this study it is reported that there exist a correlation
      between the clinically observable symptoms, the blood and urine arsenic level,
      and the arsenic intake through drinking water. An intensive study on the urinary
      arsenic levels was carried out in which the urine levels of arsenic and the urine
      sufficiency tests were performed. A composite picture of body burden of arsenic
      has been obtained by carrying out a complete biochemical analysis of a maximum
      affected family. This confirms pronounced chronic exposure of the arsenic to
      these people. A combined correlation study on the arsenic levels measured in
      whole blood, urine, hair, nails and age present a remarkable outcome.
      Accordingly, the arsenic levels in blood are negatively correlated with the urine
      arsenic levels, which indicate either the inadequacy of the renal system in
      cleaning the blood arsenic or a continuous recirculation of the accumulated
      arsenic. This is an important conclusion about arsenical metabolism in humans.
      The study also raises the issues of the prospects of complete elimination of the
      accumulated arsenic and the reversibility of the health effects. Based on the
      work in Kourikasa village we report that there are very remote chances of
      complete purging of arsenic and thus reversibility of the health effects owing to
      various factors. The paper also discusses the various issues concerning the
      chronic arsenic poisoning management in the affected locations.

PMID- 17431311
TI  - Alterations in the concentrations of liver mitochondrial DNA, cytoplasmic total
      hydrocarbon and calcium in Guinea pigs after treatment with Nigerian light crude
      oil.
AB  - The alteration of cellular calcium sequestration has been postulated to be a
      primary mechanism in the initiation of irreversible cell damage. Crude oil has
      been shown to cause concentration- dependent inhibition of calcium influx and
      mitochondrial swelling which may relate to its toxicity. Nigerian 'Bonny' Light
      Crude Oil (BLCO) is produced in the Niger-Delta region of Nigeria where oil
      spills are frequent and can endanger human-health, yet BLCO has not been studied
      in this regard. We have studied the effects of two doses of BLCO on mitochondrial
      DNA (mt.DNA), cytoplasmic total hydrocarbon concentrations (cyt.THC) and
      cytoplasmic Ca2+ (cyt.Ca2+) concentrations in livers of adult male guinea pigs
      exposed by intraperitoneal injection. The results showed that at 2.5 and 5.0
      (ml/kg bw), BLCO caused dose-related increases in mt.DNA concentrations (128% and
      485%) respectively over the controls, and cyt.THC (47.5% and 100%) respectively;
      while it caused near-100% decrease in cyt.Ca2+ concentrations (94% and 96.8%)
      respectively lower than the controls. These results suggest that BLCO caused the
      increased availability of crude oil hydrocarbons in the liver cells, and
      subsequent induction of unscheduled mt.DNA synthesis, and alteration of
      mitochondrial/endoplasmic reticulum Ca2+ sequestration or ca2+ - concentration
      gradient, leading to the inhibition of Ca2+ influx into the cytosol. These events
      may explain the probable hepatotoxicity of BLCO.

PMID- 17431312
TI  - Arsenic and chromium in canned and non-canned beverages in Nigeria: a potential
      public health concern.
AB  - Numerous studies have described environmental exposure of humans to heavy metals
      in African populations. Little is known about the exposure to heavy metal toxins
      from processed or unprocessed foods consumed in Africa, and no data exists on the
      food concentrations of arsenic and chromium, which are potential carcinogens and
      systemic toxicants. This study determined the concentrations of arsenic and
      chromium in beverages and fruit drinks commonly sold in Nigeria. Fifty samples of
      commonly consumed canned and non-canned beverages (imported and locally
      manufactured) purchased in Nigeria were digested in nitric acid and analyzed by
      atomic absorption spectrophotometry (AAS). 33.3% of the canned beverages had
      arsenic levels that exceeded the maximum contaminant level (MCL) of 0.01 mg/L set
      by U.S. EPA while 55.2% of non-canned beverages had their arsenic levels
      exceeding the MCL. The arsenic concentrations ranged from 0.003 to 0.161 mg/L for
      the canned and 0.002 to 0.261 mg/l for the non-canned beverages. Whereas 68.9% of
      the non-canned beverages showed chromium levels that exceeded the US EPA's MCL of
      0.10 mg/L, 76.2% of the canned beverages had chromium levels that were greater
      than the MCL. The concentration range of total chromium in the canned beverages
      was 0.04 to 0.59 mg/L and 0.01 to 0.55 mg/L for the non-canned beverages. The
      sources of arsenic and chromium in the commercially available beverages are
      unclear and merit further investigation. This preliminary study highlights the
      need to study the toxicological implications of chronic low-level exposure to
      heavy metals from African markets.

PMID- 17431313
TI  - System of indexes and indicators for the quality evaluation of HACCP plans based
      on the results of the official controls conducted by the Servizio di Igiene degli
      Alimenti della Nutrizione (Food and Nutrition Health Service) of the Local Health
      Authority of Foggia, Italy.
AB  - Within the realm of evaluating self-monitoring plans, developed based on the
      Hazard Analysis and Critical Control Points (HACCP) method and adopted by food
      companies, little research has been done concerning the quality of the plans. The
      Servizio di Igiene degli Alimenti e della Nutrizione (Food and Nutrition Health
      Service) of the Local Health Authority of Foggia, Italy, has conducted research
      with the aim to adopt a system of indexes and indicators for the qualitative
      evaluation of HACCP plans. The critical areas considered were the following:
      simplicity, specificity, feasibility and adherence. During the period from
      January 2004 to June 2005, the evaluation grid was used in examining 250 HACCP
      self-monitoring plans of food companies. For the analysis of the determining
      factor four groups were considered, with reference to HACCP self-monitoring plans
      designed: group 1 - with the aid of a qualified team; group 2 - with the aid of
      an unqualified team; group 3 - with the aid of an unqualified expert; group 4 -
      without the aid of an expert. The mean values of the measures elaborated decrease
      towards insufficiency moving from group 1 to group 4. In particular,
      collaboration by teams of unqualified experts brought about drafting unacceptable
      HACCP plans on the levels of specificity and adherence, with respect to the HACCP
      method. The method proposed of the analysis of the indexes and indicators
      beginning with an evaluation sheet can also help the individual company to better
      adjust contribution by internal or external professionals to the company.

PMID- 17431314
TI  - Air quality and acute respiratory illness in biomass fuel using homes in
      Bagamoyo, Tanzania.
AB  - Respiratory Diseases are public health concern worldwide. The diseases have been
      associated with air pollution especially indoor air pollution from biomass fuel
      burning in developing countries. However, researches on pollution levels and on
      association of respiratory diseases with biomass fuel pollution are limited. A
      study was therefore undertaken to characterize the levels of pollutants in
      biomass fuel using homes and examine the association between biomass fuel smoke
      exposure and Acute Respiratory Infection (ARI) disease in Nianjema village in
      Bagamoyo, Tanzania. Pollution was assessed by measuring PM10, NO2, and CO
      concentrations in kitchen, living room and outdoors. ARI prevalence was assessed
      by use of questionnaire which gathered health information for all family members
      under the study. Results showed that PM10, NO2, and CO concentrations were
      highest in the kitchen and lowest outdoors. Kitchen concentrations were highest
      in the kitchen located in the living room for all pollutants except CO. Family
      size didn't have effect on the levels measured in kitchens. Overall ARI
      prevalence for cooks and children under age 5 making up the exposed group was
      54.67% with odds ratio (OR) of 5.5; 95% CI 3.6 to 8.5 when compared with
      unexposed men and non-regular women cooks. Results of this study suggest an
      association between respiratory diseases and exposure to domestic biomass fuel
      smoke, but further studies with improved design are needed to confirm the
      association.

PMID- 17431315
TI  - Remote sensing and GIS techniques for evaluation of groundwater quality in
      municipal corporation of Hyderabad (Zone-V), India.
AB  - Groundwater quality in Hyderabad has special significance and needs great
      attention of all concerned since it is the major alternate source of domestic,
      industrial and drinking water supply. The present study monitors the ground water
      quality, relates it to the land use / land cover and maps such quality using
      Remote sensing and GIS techniques for a part of Hyderabad metropolis. Thematic
      maps for the study are prepared by visual interpretation of SOI toposheets and
      linearly enhanced fused data of IRS-ID PAN and LISS-III imagery on 1:50,000 scale
      using AutoCAD and ARC/INFO software. Physico-chemical analysis data of the
      groundwater samples collected at predetermined locations forms the attribute
      database for the study, based on which, spatial distribution maps of major water
      quality parameters are prepared using curve fitting method in Arc View GIS
      software. Water Quality Index (WQI) was then calculated to find the suitability
      of water for drinking purpose. The overall view of the water quality index of the
      present study area revealed that most of the study area with >50 standard rating
      of water quality index exhibited poor, very poor and unfit water quality except
      in places like Banjara Hills, Erragadda and Tolichowki. Appropriate methods for
      improving the water quality in affected areas have been suggested.

PMID- 17431316
TI  - Class B alkaline stabilization to achieve pathogen inactivation.
AB  - Liming is a cost-effective treatment currently employed in many Class B biosolids
      production plants in the United States. A bench scale model of lime stabilization
      was designed to evaluate the persistence of viral, bacterial and parasitic
      pathogens. The survival of fecal coliforms, Salmonella, adenovirus type 5,
      rotavirus Wa, bacteriophage MS-2, Cryptosporidium parvum oocysts, Giardia lamblia
      cysts, and Ascaris lumbricoides ova was evaluated under lime stabilization
      conditions in a water matrix. Fecal coliforms and Salmonella were undetectable
      following 2 hours of lime stabilization, demonstrating a 7-log reduction.
      Adenovirus, MS-2 and rotavirus were below detectable levels following 2 h of
      liming, demonstrating a 4-log reduction. G. lamblia cysts were also inactivated.
      A. lumbricoides ova remained viable following 72 hours of liming as did C. parvum
      oocysts. While this study confirmed that Ascaris ova are resistant to liming,
      their scarcity in sludge and low recovery efficiencies limit their use as
      indicator. The persistence of C. parvum oocysts after exposure to lime, suggests
      that this parasite would be a better choice as indicator for evaluating biosolids
      intended for land application. The studies done with adenovirus Type 5, rotavirus
      Wa and male specific bacteriophage provided preliminary data demonstrating
      similar inactivation rates. Monitoring anthropogenic viruses is a time consuming,
      labor intensive and expensive process. If further studies could demonstrate that
      phage could be used as an indicator of other enteric viruses, enhanced monitoring
      could result in greater acceptance of land application of biosolids while
      demonstrating no increased public health threat.

PMID- 17431317
TI  - Inactivation of adenovirus type 5, rotavirus Wa and male specific coliphage (MS2)
      in biosolids by lime stabilization.
AB  - The use of lime to reduce or eliminate pathogen content is a cost-effective
      treatment currently employed in many Class B biosolids production plants in the
      United States. A bench scale model of lime stabilization was designed to evaluate
      the survival of adenovirus type 5, rotavirus Wa, and the male specific
      bacteriophage, MS2, in various matrices. Each virus was initially evaluated
      independently in a reverse osmosis treated water matrix limed with an aqueous
      solution of calcium hydroxide for 24-hr at 22 +/- 5 degrees C. In all R/O water
      trials, adenovirus type 5, rotavirus Wa and MS2 were below detectable levels
      (<100.5 TCID50/mL and <1 PFU/mL respectively) following 0.1-hr of liming.
      Adenovirus type 5, rotavirus Wa, and MS2, were inoculated into composted, raw and
      previously limed matrices, representative of sludge and biosolids, to achieve a
      final concentration of approximately 104 PFU or TCID50/mL. Each matrix was limed
      for 24-hr at 22 +/- 5 degrees C and 4 +/- 2 degrees C. In all trials virus was
      below detectable levels following a 24-hr incubation. The time required for viral
      inactivation varied depending on the temperature and sample matrix. This research
      demonstrates reduction of adenovirus type 5, rotavirus Wa, and male-specific
      bacteriophage, in water, sludge and biosolids matrices following addition of an
      8% calcium hydroxide slurry to achieve a pH of 12 for 2-hr reduced to 11.5 for 22
      hr by addition of 0.1 N HCl. In these trials, MS2 was a conservative indicator of
      the efficacy of lime stabilization of adenovirus Type 5 and rotavirus Wa and
      therefore is proposed as a useful indicator organism.

PMID- 17431318
TI  - Pathogens assessment in reclaimed effluent used for industrial crops irrigation.
AB  - Reuse of treated effluent is a highly valued water source in Palestine, however
      with limited success due to public health concerns. This paper assesses the
      potential pathogens in raw, treated and reclaimed wastewater at Albireh urban
      wastewater treatment facility, and provides scientific knowledge to update the
      Palestinian reuse guidelines. Laboratory analyses of collected samples over a
      period of 4 months have indicated that the raw wastewater from Albireh city
      contained high numbers of fecal coliforms and worm eggs while 31% of the samples
      were Salmonella positive. Treated effluent suitable for restricted irrigation
      demonstrated that the plant was efficient in removing indicator bacteria, where
      fecal coliforms and fecal streptococci removal averaged 99.64% and 93.44%,
      respectively. Although not disinfected, treated effluent was free of Salmonella
      and parasites, hence safe for restricted agricultural purposes. All samples of
      the reclaimed effluent and three samples of irrigated grass were devoid of
      microbial pathogens indicating a safe use in unrestricted agricultural
      utilization. Adequate operation of wastewater treatment facilities, scientific
      updating of reuse guidelines and launching public awareness campaigns are core
      factors for successful and sustainable large-scale wastewater reuse schemes in
      Palestine.

PMID- 17431319
TI  - Intimate partner violence by men abusing and non-abusing alcohol in Poland.
AB  - Alcohol use is to one of the most of risk factors for intimate partner violence.
      The aim of this study was to check the difference of demographic characteristics
      and type of violence between of the perpetrators with a history of alcohol abuse
      (A) versus the perpetrators without a history of alcohol abuse (N). Data were
      obtained from the survey conducted in the office of the Association for Violence
      Prevention in the city of Lublin, Poland. 400 perpetrators and their victims (400
      subjects) were examined. To collect information from victims a specially designed
      questionnaire was used (VQ). Besides, another questionnaire (PQ) and The Alcohol
      Use Disorders Identification Test (AUDIT) was used to measure alcohol use in the
      perpetrators. About 76% of the perpetrators scored 8 and above (AUDIT). 84.8% of
      the perpetrators with a history of alcohol abuse (A) versus 9.2% of the
      perpetrators without a history of alcohol abuse (N) committed acts of violence
      after alcohol consumption. The A-perpetrators were more likely to be younger,
      have lower education and break law, and less likely to have permanent jobs than
      the N- perpetrators. The significant difference in the type of violence was
      found: the A-perpetrators were more likely to commit physical violence (78.2%)
      than the Nperpetrators (33.2%) and the N-perpetrators were more likely to commit
      sexual violence (32.2%) than A-perpetrators (9.14%). We would like to conclude
      that despite similarities among perpetrators, they are not a homogenous group so
      different therapeutic approach should be considered.

PMID- 17431320
TI  - A model for genetic complementation controlling the chromosomal abnormalities and
      loss of heterozygosity formation in cancer.
AB  - The relationship between the apparently random chromosomal changes found in
      aneuploidy and the genetic instability driving the progression of cancer is not
      clear. We report a test of the hypothesis that aneuploid chromosomal
      abnormalities might be selected to preserve cell-survival genes during loss of
      heterozygosity (LOH) formations which eliminate tumor suppressor genes. The LOHs
      and structurally abnormal chromosomes present in the aneuploid LoVo (colon), A549
      (lung), SUIT-2 (pancreas), and LN-18 (glioma) cancer cell lines were identified
      by single nucleotide polymorphisms (SNPs) and Spectral Karyotyping (SKY). The
      Mann-Whitney U and chi square tests were used to evaluate possible differences in
      chromosome numbers and abnormalities between the cell lines, with two-tailed P
      values of <0.01 being considered significant. The cell lines differed
      significantly in chromosome numbers and frequency of structurally abnormal
      chromosomes. The SNP analysis revealed that each cell line contained at least a
      haploid set of somatic chromosomes, consistent with our hypothesis that cell
      survival genes are widely scattered throughout the genome. Further, over 90% of
      the chromosomal abnormalities seemed to be selected, often after LOH formation,
      for gene-dosage compensation or to provide heterozygosity for specific
      chromosomal regions. These results suggest that the chromosomal changes of
      aneuploidy are not random, but may be selected to provide gene-dosage
      compensation and/or retain functional alleles of cell-survival genes during LOH
      formation.

PMID- 17431321
TI  - Elevated sister chromatid exchange frequencies in New Zealand Vietnam War
      veterans.
AB  - From July 1965 until November 1971, New Zealand Defence Force Personnel fought in
      the Vietnam War. During this time more than 76,500,000 litres of phenoxylic
      herbicides were sprayed over parts of Southern Vietnam and Laos, the most common
      being known as 'Agent Orange'. The current study aimed to ascertain whether or
      not New Zealand Vietnam War veterans show evidence of genetic disturbance arising
      as a consequence of their now confirmed exposure to these defoliants. A sample
      group of 24 New Zealand Vietnam War veterans and 23 control volunteers were
      compared using an SCE (sister chromatid exchange) analysis. The results from the
      SCE study show a highly significant difference (P < 0.001) between the mean of
      the experimental group (11.05) and the mean of a matched control group (8.18).
      The experimental group also has an exceptionally high proportion of HFCs (cells
      with high SCE frequencies) above the 95th percentile compared to the controls
      (11.0 and 0.07%, respectively). We conclude that the New Zealand Vietnam War
      veterans studied here were exposed to a clastogenic substance(s) which continues
      to exert an observable genetic effect today, and suggest that this is
      attributable to their service in Vietnam.

PMID- 17431322
TI  - A new heritable fragile site at 15q13 in a three-generation family.
AB  - Here, we describe a family ascertained through recurrent spontaneous abortions in
      which a new heritable fragile site located at 15q13 is segregating. The fragile
      site was present in nine members of a three-generation family and expressed
      spontaneously in a high proportion of the metaphases varying from 88 to 95% under
      standard culture conditions in all the carriers. This didn't change under folate
      deficiency.

PMID- 17431323
TI  - Molecular characterization of the equine ATP2A2 gene.
AB  - The mammalian ATP2A2 gene encodes a P-type cation pump located in the
      sarcoplasmic or endoplasmic reticula of muscle cells. We isolated one bacterial
      artificial chromosome (BAC) clone containing the equine ATP2A2 gene and
      determined the complete coding sequence of this gene. Cloning and
      characterization of the equine ATP2A2 gene revealed that the equine ATP2A2 gene
      consists of 20 exons. In total, 32 horses out of 16 breeds were analyzed for
      single nucleotide polymorphisms (SNPs). A mutation scan for SNPs included ten
      exons and their flanking introns. We detected in total 17 SNPs, 14 of which were
      located in introns, one in exon 9 and two in exon 20. In this report we provide
      the genomic organization and the equine ATP2A2 coding sequence and an association
      analysis for chronic pastern dermatitis using a sample of South German draft
      horses.

PMID- 17431324
TI  - Karyotype, centric fusion polymorphism and chromosomal aberrations in captive
      born mountain reedbuck (Redunca fulvorufula).
AB  - Chromosomes of fourteen captive-born mountain reedbucks (Redunca fulvorufula)
      have been investigated. The diploid chromosome number was 2n = 56 (FN = 60). The
      mountain reedbuck karyotype consists of 26 acrocentric and two biarmed chromosome
      pairs resulting from two centric fusions involving chromosomes 2 and 25, and 6
      and 10, respectively. In some animals, 57 chromosomes were detected. Variation in
      the diploid number was found to be due to polymorphism for the centric fusion
      6;10. Both X and Y chromosomes are large and acrocentric. The entire Y chromosome
      and the proximal part of the X chromosome consist of heterochromatin. The
      chromosomes X, 9 and 14 appeared to be of caprine type. Chromosome aberrations
      have been detected in two of the 14 animals investigated. A de novo formed
      Robertsonian translocation rob(6;13) was found in one female heterozygous for the
      fusion 6;10. CBG-banding revealed one block of centromeric heterochromatin in the
      de novo formed translocation rob(6;13) and also in the evolutionarily fixed
      centric fusions 6;10 and 2;25. One examined male homozygous for fusion 6;10, had
      a mosaic 56,XY/57,XYY karyotype, with 11% of analyzed cells containing two Y
      chromosomes. The findings were confirmed by cross-species fluorescence in situ
      hybridization (FISH) with bovine (Bos taurus L.) chromosome painting probes. The
      study demonstrates the relevance of cytogenetic screening in captive animals from
      zoological gardens.

PMID- 17431325
TI  - Systematics and phylogeny of West African gerbils of the genus Gerbilliscus
      (Muridae: Gerbillinae) inferred from comparative G- and C-banding chromosomal
      analyses.
AB  - Comparative analysis of the G- and C-banding patterns in six morphologically
      similar species of the genus Gerbilliscus(G. gambianus, G. guineae, G. kempi,
      Gerbilliscus sp., G. robustus and G. leucogaster) and one belonging to the genus
      Gerbillurus (G. tytonis) from 27 West, East and South African localities was
      carried out. Our study revealed that 17 rearrangements comprising seven fissions,
      five translocations and five inversions occurred in the evolution of this group,
      with 1-13 rearrangements differentiating the various species. In addition the
      unusually large sex chromosomes appear to be species-specific as judged by size
      and morphology reflecting structural rearrangements as well as the variable
      presence of a large amount of C-heterochromatin found in each species at a
      particular chromosomal location. These karyotypic features allow us to recognize
      five distinct species in West Africa (compared to the two recognized in recent
      taxonomic lists) and to roughly delimit their geographical distributions. The
      pattern of phylogenetic relationships inferred from a cladistic analysis of the
      chromosomal data is in good agreement with recent molecular phylogenetic studies
      that recognize a West African species group within the genus Gerbilliscus, and
      the monophyly of both Gerbilliscus and Gerbillurus.

PMID- 17431326
TI  - Using a Bayesian method to assign individuals to karyotypic taxa in shrew hybrid
      zones.
AB  - Individuals sampled in hybrid zones are usually analysed according to their
      sampling locality, morphology, behaviour or karyotype. But the increasing
      availability of genetic information more and more favours its use for individual
      sorting purposes and numerous assignment methods based on the genetic composition
      of individuals have been developed. The shrews of the Sorex araneus group offer
      good opportunities to test the genetic assignment on individuals identified by
      their karyotype. Here we explored the potential and efficiency of a Bayesian
      assignment method combined or not with a reference dataset to study admixture and
      individual assignment in the difficult context of two hybrid zones between
      karyotypic species of the Sorex araneus group. As a whole, we assigned more than
      80% of the individuals to their respective karyotypic categories (i.e. 'pure'
      species or hybrids). This assignment level is comparable to what was obtained for
      the same species away from hybrid zones. Additionally, we showed that the
      assignment result for several individuals was strongly affected by the inclusion
      or not of a reference dataset. This highlights the importance of such comparisons
      when analysing hybrid zones. Finally, differences between the admixture levels
      detected in both hybrid zones support the hypothesis of an impact of chromosomal
      rearrangements on gene flow.

PMID- 17431327
TI  - Intergenomic translocations in unisexual salamanders of the genus Ambystoma
      (Amphibia, Caudata).
AB  - Intergenomic interactions that include homoeologous recombinations and
      intergenomic translocations are commonly observed in plant allopolyploids.
      Homoeologous recombinations have recently been documented in unisexual
      salamanders in the genus Ambystoma and revealed exchanged chromosomal segments
      between A. laterale and A.jeffersonianum genomes in individual unisexuals. We
      discovered intergenomic translocations in two widespread unisexual triploids
      A.laterale--2 jeffersonianum (or LJJ) and its tetraploid derivative A.laterale--3
      jeffersonianum (or LJJJ) by genomic in situ hybridization (GISH). Two different
      types of intergenomic translocations were observed in two unisexual populations
      and one contained novel chromosomes generated by an intergenomic reciprocal
      translocation. We also observed chromosome deletions in several individuals and
      these chromosome fragmentations were all derived from the A. jeffersonianum
      genome. These observed intergenomic reciprocal translocations are believed to be
      caused by non-homologous pairing during meiosis followed by breakage-rejoining
      events. Genomes of unisexual Ambystoma undergo complicated structural changes
      that include various intergenomic exchanges that offer unisexuals genetic and
      phenotypic complexity to escape their evolutionary demise. Unisexual Ambystoma
      have persisted as natural nuclear genomic hybrids for about four million years.
      These unisexuals provide a vertebrate model system to examine the interaction of
      distinct genomes and to evaluate the corresponding genetic, developmental and
      evolutionary implications of intergenomic exchanges. Intergenomic translocations
      and homoeologous recombinations appear to be frequent chromosome reconstruction
      events among unisexual Ambystoma.

PMID- 17431328
TI  - Identification of the sex chromosome pair in chum salmon (Oncorhynchus keta) and
      pink salmon (Oncorhynchus gorbuscha).
AB  - Fluorescence in situ hybridization (FISH) using a probe to the male-specific GH-Y
      (growth hormone pseudogene) was used to identify the Y chromosome in the
      karyotypes of chum salmon (Oncorhynchus keta) and pink salmon (Oncorhynchus
      gorbuscha). The sex chromosome pair is a small acrocentric chromosome pair in
      chum salmon and the smallest metacentric chromosome pair in pink salmon. Both of
      these chromosome pairs are morphologically different from the sex chromosome
      pairs in chinook salmon (Oncorhynchus tshawytscha) and coho salmon (Oncorhynchus
      kisutch). The 5S rRNA genes are on multiple chromosome pairs including the sex
      chromosome pair in chum salmon, but at the centromeres of two autosomal
      metacentric pairs in pink salmon. The sex chromosome pairs and the chromosomal
      locations of the 5S rDNA appear to be different in all five of the North American
      Pacific salmon species and rainbow trout. The implications of these results for
      evolution of sex chromosomes in salmonids are discussed.

PMID- 17431329
TI  - X-Y-autosome translocation, chromosome compaction, NOR expression and
      heterochromatin insulation in the Scarabaeid beetle Dynastes hercules hercules.
AB  - The karyotype of the giant beetle Dynastes hercules hercules is composed of only
      16 autosomes and large sex chromosomes. Meiotic studies in the males showed that
      a large part of the sex chromosomes undergo synapsis at pachynema similarly to
      autosomes, demonstrating that both derived from an autosome-gonosome
      translocation. Therefore, karyotype formula is 18,neoXY. The heterochromatisation
      of the neoX short arm at pachynema indicates that it corresponds to the ancestral
      X. It carries the nucleolar organizer region (NOR) in its proximal part, which is
      undercondensed, especially in male mitotic and meiotic cells. In female mitotic
      cells, both NOR staining and undercondensation were more difficult to observe in
      the neoX short arms. In somatic interphase nuclei, NOR expression strongly varies
      with the sex. Two separated compact groups of silver dots were observed in female
      nuclei, while a single dispersed and large group of silver deposit exists in the
      males. Both the lower condensation and the higher NOR expression of the single
      neoX of the males, compared to each of the two neoXs of the females, is
      interpreted to be a consequence of dosage compensation, a mechanism not yet
      described in Coleoptera. In mammals as well as in Coleoptera, the carriers of
      gonosome-autosome translocations not exhibiting deleterious phenotypes show
      constitutive heterochromatin at the autosome-gonosome junction. Thus,
      heterochromatin may play an important universal role by clearly separating
      chromosome segments with different regulations of gene expression, such as
      inactivation or dosage compensation of the X chromosome on the one side and a
      conventional autosomal structure on the other side.

PMID- 17431330
TI  - Histone H2AX phosphorylation is associated with most meiotic events in
      grasshopper.
AB  - It is widely accepted that the H2AX histone in its phosphorylated form (gamma
      H2AX) is related to the repair of DNA double-strand breaks (DSBs). In several
      organisms, gamma-H2AX presence has been demonstrated in meiotic processes such as
      recombination and sex chromosome inactivation during prophase I (from leptotene
      to pachytene). To test whether gamma-H2AX is present beyond pachytene, we have
      analysed the complete sequence of changes in H2AX phosphorylation during meiosis
      in grasshopper, a model organism for meiotic studies at the cytological level. We
      show the presence of phosphorylated H2AX during most of meiosis, with the
      exception only of diplotene and the end of each meiotic division. During the
      first meiotic division, gamma-H2AX is associated with i) recombination, as
      deduced from its presence in leptotene-zygotene over all chromosome length, ii) X
      chromosome inactivation, since at pachytene gamma-H2AX is present in the X
      chromosome only, and iii) chromosome segregation, as deduced from gamma-H2AX
      presence in centromere regions at first metaphase-anaphase. During second meiotic
      division, gamma-H2AX was very abundant at most chromosome lengths from metaphase
      to telophase, suggesting its possible association with the maintenance of
      chromosome condensation and segregation.

PMID- 17431331
TI  - Mapping of the silver gene in mink and its association with the dilution gene in
      dog.
AB  - In mink, recessive and dominant genes carry standard colors from generation to
      generation but breeding and cross breeding of naturally occurring mutations
      (color changes) has resulted in farmed animals bearing colors that do not exist
      in nature. The silver blue color type is one of the most used recessive mutations
      within mink fur farming being part of some of the popular color types which
      combine more recessive mutations. We report here the mapping of the 'silver' gene
      on MVI3 by means of the first linkage genetic map in the American mink (Mustela
      vison). A Canis familiaris BAC clone containing the melanophilin gene (which
      generates 'silver-like' phenotype in dog) was in situ cross-hybridized onto the
      mink chromosomes and the result strongly supports the linkage data. Therefore the
      silver phenotype in the American mink presumably involves the melanophilin gene
      (MLPH).

PMID- 17431332
TI  - Pseudodicentric 22;Y translocation transmitted through four generations of a
      large family without phenotypic repercussion.
AB  - The most frequent Y-autosome translocations involve an acrocentric autosome and
      they are frequently familial with neither phenotypic nor reproductive
      repercussion. However, different Y-autosome translocations have been related to
      infertility, due to abnormal pairing of the X and Y chromosomes at meiosis and an
      abnormal XY-body formation or by the disruption of the AZFs (Azoospermic Factor).
      Rare forms of Y-autosome translocations are those resulting in an unbalanced 45
      chromosome karyotype that includes a dicentric Y+autosome chromosome. We describe
      a new case of a familial pseudodicentric 22;Y that is carried by 19 male members
      of a large family without phenotypic repercussion. Cytogenetic analysis,
      fluorescence in situ hybridisation (FISH) and subtelomeric Multiplex Ligation
      dependent Probe Amplification (MLPA) assay have been performed. All male members
      of the family showed the karyotype 45,X,psu dic(22;Y)(p11.2;qter).ish psu
      dic(22;Y) (SRY+,DYZ3+,D14/D22Z1+). In conclusion, the presence of the dicentric
      chromosome in the male members of the family reported does not seem to interfere
      with the correct progression of spermatogenesis.

PMID- 17431334
TI  - [Current status and problems of tailor-made medicine in anticancer therapy].
AB  - Tailor-made medicine is a key concept in achieving a successful outcome for
      individual patients with malignant disease. Identifying the appropriate patient,
      i.e., "How to select patients", is the first concept of tailor-made medicine. In
      recent years, molecular target drugs have been developed rapidly and over a broad
      spectrum. The candidate patients for drugs are selected by particular biomarkers
      based on theoretical evidence. Moreover, conventional individualized methods such
      as TNM classification, pathological findings and patient background including
      performance status, and organ functions, are also important to correctly identify
      the patients. Identifying the appropriate therapy, i.e., "How to treat", is the
      next concept. Drug sensitivity tests and prediction models using DNA micro array
      are still under development and not available at bedside. Chemotherapy drug
      dosages are adjusted according to body surface area with a lack of scientific
      data. There have been some attempts to establish calculation formulas for
      modification of drugs. The Calvert formula is the best-known, however, it may not
      be used correctly in Japan because of the difference in the methods for
      estimating creatinine as well as ethnic differences.
      pharmacogenomics/pharmacogenetics is the front-line approach of modern
      chemotherapy that analyzes genomic information and
      pharmacokinetic/pharmacodynamic findings. This approach is achieving adaptable
      results for cancer treatment practice. Finally, for tailor-made medicine, we must
      develop genomic approach in both evaluating tumor characteristics and
      establishing adequate therapy, and have to combine all possible information
      including conventional TNM classification and pathological findings.

PMID- 17431335
TI  - [Treatment of malignant pleural mesothelioma].
AB  - In Japan, it is predicted that mesothelioma will rapidly increase in the future.
      Malignant pleural mesothelioma that accounts for approximately 90% of
      mesothelioma as a whole has a median survival time of approximately nine months
      which is considered a poor prognosis. As for the treatment of this
      disease,extrapleural pneumonectomy or pleurectomy/decortication are available for
      those patients who can be surgically operated on. However, since a complete cure
      rate is low when only surgical treatment is performed, generally a multimodality
      treatment is performed wherein chemotherapy and/or radiotherapy are combined. For
      chemotherapy, a large-scale randomized phase III study demonstrated that a
      treatment using two agents: pemetrexed, which is a new multitargeted antifolate,
      and cisplatin is effective. Pemetrexed will be the drug of first choice for
      mesothelioma in the future. As other treatment methods, chemohyperthermia,
      treatments using various kinds of cytokines and angiogenesis inhibitors, genetic
      treatment and photodynamic therapy have been attempted. The current treatment
      results for this disease are very poor, and there has been a strong demand for
      establishing an effective treatment method.

PMID- 17431336
TI  - [Non-cisplatin based chemotherapy in advanced non-small cell lung cancer].
AB  - Platinum-based, especially cisplatin-based chemotherapy is still the backbone of
      combination chemotherapy for advanced non-small cell lung cancer (NSCLC). Several
      combinations of cisplatin-or carboplatin-based chemotherapy are widely used in
      the treatment of advanced NSCLC. However, cisplatin is associated with
      considerable toxicity and large amount of fluid infusion that may lead to
      reluctance on the part of both physicians and patients to accept cisplatin-based
      chemotherapy for incurable NSCLC. Carboplatin has also been a widely used agent
      in the treatment of NSCLC instead of cisplatin. However, it is controversial
      whether carboplatin has the same activity as cisplatin or not. Several reports
      showed that carboplatin was not superior but almost equal to cisplatin in terms
      of survival. Third generation agents have been developed in the past decades
      including gemcitabine, paclitaxel, docetaxel, vinorelbine and irinotecan. All of
      them have promising levels of anti-tumor activity for NSCLC and the development
      of non-platinum-based chemotherapy was expected. Several randomized trials and
      meta-analysis have compared platinum-based combination chemotherapy with non
      platinum chemotherapy based on various combinations of these third generation
      agents. The analysis of these trials indicated that non-platinum based
      chemotherapy was not superior to platinum-based chemotherapy for survival time
      but less toxicity. Third-generation-based non-platinum combinations are still
      treatment options for advanced NSCLC patients who are not eligible for platinum
      based chemotherapy.

PMID- 17431337
TI  - [Outpatient chemotherapy for lung cancer].
AB  - In order to maintain the QOL in lung cancer patients and also save on medical
      costs, chemotherapy should be performed on an outpatient basis as much as
      possible. If the performance status is good and their residence is nearby, then
      not only in the case of small cell lung cancer or unresectable non-small cell
      lung cancer, but also including postoperative adjuvant chemotherapy for non-small
      cell lung cancer, in all such suitable cases, chemotherapy can be performed on an
      outpatient basis. For example, by performing outpatient chemotherapy in moderate
      amounts for older people, the survival can be improved while maintaining the QOL.
      However,a single dose of cisplatin 60 to 80 mg/m(2) requires a high volume iv
      infusion, and the first chemotherapy treatment needs to be carried out in the
      hospital for nausea and vomiting control. For a regimen of combined anticancer
      drugs other than cisplatin and including carboplatin, such as paclitaxel,
      docetaxel, irinotecan, gemcitabine or vinorelbine, the required iv time is short,
      side effects such as nausea or vomiting are less severe,and it is easily
      performed on an outpatient basis. An oral anticancer drug, gefitinib, or S-1 can
      also be an effective choice for non-small cell lung cancer. Since lung cancer
      patients tend to be susceptible to obstructive pneumonia or pneumonia from
      opportunistic infections, these need particular attention at the time of
      neutropenia. In addition, strict caution is required in order to prevent
      prescription or medication errors, or medical accidents such as leakage of the
      intravenous drip. If severe side effects occur, then a system must be prepared in
      which the patient can make contact promptly in emergency situations and thus can
      be hospitalized as necessary. Outpatient chemotherapy for lung cancers is
      increasing in Japan, however, there are many issues including insufficient staff,
      overworked staff, or situations where home nursing care places a heavy burden on
      the family. The assignment of sufficient medical treatment fees, the
      rationalization of work responsibilities or further development of home
      assistance systems are therefore eagerly anticipated.

PMID- 17431339
TI  - [Radiation therapy for lung cancer].
AB  - Radiation therapy is one of the most important modalities for the treatment of
      lung cancer. Current progress of radiation therapy in cooperation with the
      development of physics and biology is remarkable. The techniques of three
      dimensional treatment planning and three-dimensional conformal radiotherapy (3D
      CRT) have facilitated the use of higher radiation doses. Patients with early
      stage non-small cell lung cancer (NSCLC) are candidates for curative surgical
      resection. However, the number of elderly patients has been increasing, and these
      patients often have medical contraindications that prevent curative surgery.
      Recently, several clinical trials on stereotactic body radiotherapy (SBRT) using
      the 3D-CRT technique for solitary lung tumors have been reported. The local
      control rate for stage I disease is more than 90%, and survival rates are
      promising. Now a prospective multi-institutional trial is ongoing to determine
      whether this modality can become a standard treatment for inoperable patients or
      an alternative to lobetectomy. For locally advanced NSCLC, unfortunately, recent
      studies have demonstrated that conventional therapies may have reached a
      therapeutic plateau. Now several radiation dose escalation studies utilizing
      conventional fractionation and 3D-CRT techniques are ongoing. The strategies of
      almost all of these trials are to eliminate elective nodal irradiation and
      deliver a higher dose of radiation to gross tumor volume while sparing normal
      tissues. Preliminary experience has resulted in promising survival, but should be
      developed to integrate into the combined treatment to completely control both
      local disease and other microscopically involved lesions. The combination of
      novel chemotherapeutic agents and molecular targeting therapies with radiation
      therapy is being investigated. Development of molecular imaging techniques is
      expected to facilitate more selective dose escalation in tumors.

PMID- 17431338
TI  - [Prediction of effectiveness of EGFR tyrosine kinase inhibitors for the patients
      with by EGFR mutations].
AB  - EGFR-TKI has been synthesized as a potential target for cancer therapy because
      EGFR is overexpressed and associated with poor prognosis of lung cancer. It was
      reported that EGFR mutations were more sensitive to EGFRTKI than those without
      the mutations among lung cancer patients. A subgroup of patients of Asian origin,
      female sex, adenocarcinoma, and no history of smoking were significantly
      associated with a high rate of EGFR mutations. These patients with EGFR mutations
      were not only favorable responders but also had a longer survival than without.
      In this article, we discuss the EGFR-TKI predictive factors by EGFR mutations.

PMID- 17431340
TI  - [Translational research in patients with lung cancer--clinical application of NKT
      cell immunotherapy].
AB  - Human V alpha 24 natural killer T (NKT) cells bearing an invariant V alpha 24 J
      alpha Q antigen receptor, the counterpart of murine V alpha 14 NKT cells, are
      activated by a specific ligand, alpha-galactosylceramide (alpha GalCer; KRN
      7000), in a CD 1 d-dependent manner. Previous findings showed that alpha GalCer
      pulsed dendritic cells (DCs) exerted a strong antitumor activity in the mouse
      tumor metastatic models, and intravenous administration of alpha GalCer-pulsed
      DCs led to V alpha 14 NKT cell expansion in the lung. With these results, we
      performed a phase I dose escalation study of alpha GalCer-pulsed DCs treatment in
      patients with lung cancer. Patients with advanced non-small cell lung cancer or
      recurrent lung cancer received intravenous injection of alpha GalCer pulsed
      dendritic cell immune therapy to test the safety, feasibility, and clinical
      response. Immunomonitoring was also performed in all completed cases. Eleven
      patients were enrolled in this study, None of whom experienced severe adverse
      events. Peripheral blood V alpha 24 NKT cells dramatically increased after the
      first and second injection of alpha GalCer pulsed DCs in one patient of level 3.
      The clinical trial of alpha GalCer-pulsed DCs administration is well
      tolerated,and this therapy has been carried out safely. To obtain more conclusive
      findings about immune responses and antitumor responses, a phase I-II study with
      greater numbers of patients is ongoing.

PMID- 17431341
TI  - [Pathological evaluation of neoadjuvant chemotherapy with low-dose FP therapy for
      advanced gastric cancer].
AB  - In the present study, we evaluated the pathological effects of preoperative
      chemotherapy with low-dose CDDP and 5-FU (low-dose FP therapy) in patients with
      advanced gastric cancer. 50 patients diagnosed as advanced gastric cancer were
      administered continuous infusion of 5-FU (300 mg/m(2)/day, x 14 days) and
      intermittent infusion of CDDP (3 mg/m(2)/day, day 1-5 and 8-12) before surgery.
      The pathological effects were considered comparatively regarding the response
      rate of chemotherapy for gastric cancer between primary lesions and metastasis of
      lymph nodes and the rate of downstaging cases with low-dose FP therapy. The rates
      of effective cases were 26% (primary lesions) and 28% (lymph nodes).
      Furthermore,in the same patient,the results of low-dose FP therapy with primary
      tumor were more effective than those of lymph nodes (the rates of effective cases
      were 34% and 19%, respectively). The rate of downstaging cases with low-dose FP
      therapy for gastric cancer was 6%, histologically. These results indicate low
      dose FP therapy for gastric cancer is promising for effective clinical management
      of advanced gastric cancer in preoperative treatment.

PMID- 17431342
TI  - [A phase I study of postoperative combination therapy with TS-1 and low dose
      cisplatin against stage IV gastric carcinoma].
AB  - A dose-escalation study was conducted for postoperative patients with stage IV
      gastric cancer to determine the recommended dose of daily intravenous cisplatin
      combined with a fixed dose of TS-1. TS-1 was administered orally twice daily for
      2 weeks followed by a 1-week rest. The dose of TS-1 was based on the body surface
      area (BSA) as follows: 80 mg/day for BSA less than 1.25, 100 mg/day for BSA 1.25
      to less than 1.50, and 120 mg/day for BSA 1.5 or more. Three dose levels of
      cisplatin (2, 4, 6 mg/m(2)) were studied, and two courses were performed.
      Cisplatin was infused on day 1-5 and 8-12 for 30 minutes. The National Cancer
      Institute common toxicity criteria (NCI-CTC Version 3) were used to evaluate the
      grade of toxicity. Three patients enrolled in each level. Dose escalation was
      performed when dose-limiting toxicities (DLT) were seen in 0/3, and 3 more cases
      of the same level were added when DLTs were seen 1-2/3. Maximum-tolerated dose
      (MTD) were determined when DLTs were seen in 3 cases. DLTs were not recorded
      during the administration of CDDP up to 4 mg/m(2). However, DLTs were seen 3/3 at
      level 3. From these results, cisplatin of 4 mg/m(2)was determined to be the
      recommended dose (RD) in this protocol for postoperative stage IV gastric
      carcinoma.

PMID- 17431343
TI  - [Clinical efficacy of biweekly paclitaxel and S-1 regimen for 14 gastric cancer
      patients with liver metastases].
AB  - We evaluated efficacy of biweekly paclitaxel and S-1 for advanced gastric cancer
      patients with liver metastases. A total of 14 patients had multiple liver
      metastases. None of whom received chemotherapy before the current regimen. The
      patients were given 80 mg-130 mg/m(2) of paclitaxel every two weeks and 80 mg of
      S-1 during the first two weeks. Chemotherapeutic efficacy for liver metastases
      was 50%. The 3-year-survival rate of the 14 patients was 50%, which was
      significantly higher than that of historical control patients (p<0.01). Two
      patients received gastrectomy with curative intent. Histological exploration
      revealed disappearance of liver metastases. In conclusion, biweekly paclitaxel+S
      1 regimen was one of the promising therapies for advanced gastric cancer patients
      with liver metastases.

PMID- 17431344
TI  - [Reduction of oxaliplatin-related neurotoxicity by calcium and magnesium
      infusions].
AB  - PURPOSE: Oxaliplatin in combination with infusional 5-fluorouracil/leucovorin
      (FOLFOX) have emerged as the standard of care in the therapy of advanced-stage
      colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity. We
      decided to use Ca and Mg for prevention of oxaliplatin-related neurotoxicity with
      reference to the report of Gamelin et al. METHODS: The subjects were 14 patients
      with metastatic colorectal cancer. Oxaliplatin (85 mg/m(2)) was given
      intravenously as FOLFOX regimen. All 14 patients received infusions of Ca
      gluconate and Mg sulfate before and after oxaliplatin. RESULTS: Only 1 patient
      had grade 3 toxicity (nausea and vomiting). Sensory neuropathy occurred in 8
      patients (57.1%). There was no neurotoxicity with functional impairment in this
      study. Sensory neuropathy hardly occurred before 4 cycles. CONCLUSIONS: Ca/Mg
      infusions seem to prevent acute oxaliplatin-induced neurotoxic.

PMID- 17431345
TI  - [Apoptotic mechanisms induced in breast cancer cells by vinorelbine].
AB  - Vinorelbine (VNB) is one of new semi-synthesized vinka alkaloids developed in
      France, of which anti-tumor activity is susceptible mainly to non-small cell lung
      cancer and breast cancer. Moreover, its clinical efficacy has been noted from
      single-agent therapy or combination therapy with taxanes. It is assumed that VNB
      selectively acts on tubulin which elaborates microtubules, strands the cells at G
      1 phase and interferes with the mitosis. VNB has unique anti-tumor activity as an
      antimicrotubule agent and is expected to be available for treatment of multi-drug
      resistant tumors. In this report, we demonstrate that VNB, as an antimicrotubule
      agent, induces apoptosis in breast cancer cell line, MX-1 via a mitochondrial
      pathway.

PMID- 17431346
TI  - [Cost-effectiveness analysis of maximum androgen blockade for Japanese men with
      advanced prostate cancer].
AB  - Like other countries, Japan is facing the problem of rising medical costs
      associated with aging of the population, and therefore the cost-effectiveness of
      medicines has become increasingly important. Maximum androgen blockade (MAB)
      therapy, which is being widely used for advanced prostate cancer, has proved
      useful in clinical studies but it requires the additional use of an anti-androgen
      in contrast with luteinizing hormone releasing hormone agonist (LHRHa)
      monotherapy, raising a concern about the increase medical costs. Thus, based on
      the results of a Japanese Phase III study of bicalutamide we performed a cost
      effectiveness analysis. We constructed a Markov model to express the changes in
      prognosis following MAB therapy and LHRHa monotherapy for advanced prostate
      cancer and the cost and effectiveness (survival) were simulated. As a result, the
      expected costs of MAB therapy and LHRHa monotherapy were 5,240,000 yen and
      3,660,000 yen, respectively, with expected survival durations of 7.45 and 6.44
      years. The incremental cost-effectiveness ratio for MAB therapy was 1,560,000
      yen/life-year saved, lower than the established threshold (6,000,000 yen/life
      year saved), and a sensitivity analysis confirmed the robustness of this result.
      Therefore, the incremental cost of bicalutamide was considered worth it in view
      of the therapeutic effect, suggesting that MAB therapy is a highly cost-effective
      therapy.

PMID- 17431347
TI  - [A successful case of lower gingival cancer with pulmonary metastases by adjuvant
      chemotherapy including paclitaxel, cisplatin and 5-fluorouracil following a
      surgical procedure].
AB  - We report a successful case with pulmonary metastases from lower gingival cancer
      by a surgical procedure and four cycles of adjuvant chemotherapy including
      paclitaxel (PTX), cisplatin (CDDP) and 5-fluorouracil (5-FU). A 47-year-old woman
      underwent chemotherapy with CDDP and 5-FU after an operation for lower gingival
      squamous cell carcinoma and its neck lymph node metastases. At 4 months from the
      initial treatment, pulmonary metastatic lesion was resected by video-assisted
      thoracoscopic surgery (VATS). Fourteen months later, pulmonary metastatic lesion
      was found and dissected again using VATS. Furthermore, the patient was treated by
      adjuvant chemotherapy with PTX 135 mg/m(2) over 3 hours on day 1, CDDP 75
      mg/m(2)on day 2 and 5-FU 350 mg/m(2)/day by continuous intravenous infusion on
      day 2 through 5. After that, there is no evidence of pulmonary recurrence for
      more than six years.

PMID- 17431348
TI  - [A case of scirrhous gastric cancer with peritoneal metastases successfully
      treated by combined chemotherapy of biweekly paclitaxel and TS-1 followed by
      curative resection].
AB  - The patient was a 50-year-old male with advanced gastric cancer. Laparoscopy
      showed peritoneal metastases. We thought a complete resection would be difficult,
      so he was given neoadjuvant chemotherapy combined with paclitaxel (200 mg, day 1,
      15) and TS-1 (120 mg/day, for days 1-14 with a 2-week rest). After 3 courses of
      this neoadjuvant chemotherapy, the tumor decreased in size. Laparoscopy showed no
      peritoneal metastasis, and thus a total gastrectomy with splenectomy and D 2
      lymph node dissection was performed. The pathological diagnosis was sig, LM, type
      4, pT 3 (SE), sci, INFgamma, ly 0, v 0, pN 0, pPM (-), pDM (-), and the antitumor
      efficacy of this therapy was Grade 0 histologically. Combined chemotherapy of
      biweekly paclitaxel and TS-1 was thought to be an effective neoadjuvant
      chemotherapy for advanced gastric cancer in this case.

PMID- 17431349
TI  - [A case of advanced gastric cancer with obstructive jaundice due to multiple
      liver metastasis successfully treated with the following combination therapy of
      CPT-11 and cisplatin after combination therapy of paclitaxel and TS-1].
AB  - A 60-year-old man, who had been admitted to another hospital with complaints of
      constipation, abdominal fullness and appetite loss, was referred to our hospital
      for further examination and therapy. The patient was diagnosed as advanced
      gastric cancer (type-3) with multiple liver metastasis and obstructive jaundice.
      He was treated with combination therapy of paclitaxel and TS-1 (60 mg/m(2)/day of
      paclitaxel was iv administered on day 1 and 8, and TS-1 of 80 mg/m(2)/day was
      orally administered for 2 weeks followed by one drug-free week), and showed a
      remarkable response. However, because of ascites, elevated serum CEA level and
      resistance in the liver metastasis and gastric region, we attempted two courses
      of combination therapy with high-dose CPT-11 and cisplatin (70 mg/m(2)/day of CPT
      11 was administered iv on day 1 and 15, and 80 mg/m(2)/day of cisplatin on day 1
      followed by two drug-free weeks) which showed a remarkable response. Two courses
      of combination therapy with low-dose CPT-11 and cisplatin (60 mg/m(2)/day of CPT
      11 and 30 mg/m(2)/day of cisplatin were administered iv on day 1 and 15 followed
      by two drug-free weeks) on an outpatient basis. However, the patient showed
      resistance to the latter combination therapy, increased ascites due to suspicious
      peritonitis carcinomatosa and obvious re-growth of the metastatic tumors in the
      liver. He died on May 23, 2006, about ten months after initial diagnosis. We
      reported a case of successful treatment of combination chemotherapy for advanced
      gastric cancer with obstructive jaundice due to progressive multiple metastatic
      tumors in the liver and obtained comparative long-term survival maintaining high
      quality of life.

PMID- 17431350
TI  - [A case report of gastric small cell carcinoma with long survival time by
      adjuvant chemotherapy--reports of chemotherapy regimens for gastric small cell
      carcinoma].
AB  - Gastric small cell carcinomas are rather rare. The incidence of small cell
      carcinomas of all histological types of gastric tumors is about 0.1%. Small cell
      carcinoma is a very aggressive cancer with a poor prognosis,and there is no
      effective chemotherapy to date. We experienced a case of small cell carcinoma of
      the stomach with relatively long survival from combination chemotherapy. A 75
      year-old man underwent total gastrectomy, and liver metastasis was recognized 5
      months postoperatively. We used combination chemotherapy with
      tegafur/gimeracil/oteracil potassium+cisplatin and irinotecan
      hydrochloride+cisplatin, and he has obtained a long survival time. We should
      gather more chemotherapy cases and establish some effective regimens for small
      cell carcinoma of the stomach.

PMID- 17431351
TI  - [A case of TS-1 resistant recurrent gastric cancer with lung metastasis
      responding to TS-1 and irinotecan combination therapy].
AB  - We report a case of TS-1-resistant recurrent gastric cancer with lung metastasis
      responding to TS-1 and irinotecan (CPT-11) combination therapy. A 72-year-old man
      underwent total gastrectomy with pancreaticosplenectomy for advanced gastric
      cancer on October 18, 2001, and partial hepatectomy for postoperative liver
      metastasis on August 22, 2002. In March 2004, a chest computed tomography scan
      revealed metastatic lesions in the bilateral lungs, and he received a single
      administration of TS-1, resulting in partial response. After 13 courses, this
      therapy was discontinued due to progressive disease. Then,TS-1 and CPT-11
      combination therapy was chosen as the second-line chemotherapy. After 4 courses,
      a partial response was obtained in lung metastasis, and thereafter has been
      maintained. He has been treated on an outpatient basis because of no grade 3 or
      severer adverse reactions. TS-1 and CPT-11 combination therapy could be a
      promising regimen as the second-line chemotherapy for gastric cancer resistant to
      TS-1.

PMID- 17431352
TI  - A case of suspected S-1 induced interstitial pneumonia.
AB  - A 37-year-old female with advanced gastric cancer and liver metastases was
      treated with S-1. Since the patient noticed a transient cough and low-grade fever
      in the middle of the third course of treatment, administration of S-1 was
      discontinued. Her symptoms resolved in three days, and the fourth course was
      started again. However, two weeks later she was hospitalized with non-productive
      coughing, and exertional dyspnea with severe hypoxemia. CT scan showed minimal
      ground glass shadow in bilateral lungs and that the multiple liver metastases
      were strikingly reduced in size. CT scan obtained on the third hospital day
      showed extensive ground glass and consolidative changes in bilateral lungs. She
      died on the same day despite high-dose steroid therapy. Although a definite
      causal relationship between pneumonia and S-1 is still unproven, S-1-induced
      pneumonia needs to be considered in the differential diagnosis when patients
      present with dyspnea are treated with S-1.

PMID- 17431353
TI  - [Successful low-dose TS-1 administration in an elderly colon cancer patient with
      liver metastasis].
AB  - An 85-year-old man, who had undergone right hemicolectomy and partial hepatectomy
      for caecum cancer with liver metastasis, was diagnosed with recurrent multiple
      liver metastasis 10 months after surgery. TS-1 administration at a dose of 80
      mg/day induced grade 3 anorexia, and after complete recovery from the adverse
      reaction, it was converted to a low-dose TS-1 administration at 40 mg/day. This
      treatment reduced the diameter of the liver metastasis and was continued for ten
      months without any adverse reaction. Pharmacokinetic analysis in this patient on
      low-dose TS-1 showed that Cmax and AUC of 5-chloro-2,4-dihydroxypyridine (CDHP)
      were equivalent to the values reported in cancer patients with normal renal
      function receiving standard-dose administration. TS-1 therapy may provide a safe
      and effective alternative to chemotherapy for elderly patients with advanced
      colorectal carcinoma. Pharmacokinetic analysis could be useful for determining
      the ideal dose of TS-1.

PMID- 17431354
TI  - [Second-or third-line chemotherapy with CPT-11+TS-1 for 5 cases of metastatic and
      recurrent colorectal cancer].
AB  - The 3-drug regimen of CPT-11+5-FU+l-LV is generally used for metastatic and/or
      recurrent colorectal cancer. We have applied this treatment as the first-line
      intervention in our hospital. However,when the efficacy is reduced we try
      chemotherapy using CPT-11+TS-1 for 5 outpatients as second- or third-line
      chemotherapy. Decreased CEA levels were subsequently observed in 4 of 5 cases. In
      addition, 2 cases exhibited grade 1 or 2 adverse effects, but no case developed
      neutropenia. We could expect such effects even for patients after only 5-FU, and
      this treatment may be performed safely on ambulatory patients.

PMID- 17431355
TI  - [A long survival case of sigmoid colon cancer patient with initially unresectable
      hepatic metastases].
AB  - The prognosis of a colorectal cancer patient with unresectable hepatic metastases
      is extremely poor. To improve the prognosis, when the hepatic metastases were
      initially unresectable, we performed second-look hepatectomy (s-l hepatectomy)
      after neoadjuvant hepatic arterial 5-FU infusion plus UFT (HAI-PMC). Here, we
      report the case of a sigmoid colon cancer patient with initially unresectable
      hepatic metastases showing a prolonged survival (6.5 years) by second-look
      operation after HAI-PMC. A 57-year-old woman was diagnosed with sigmoid colon
      cancer with unresectable liver metastases. Sigmoidectomy and hepatic arterial
      catheterization were performed in the initial operation, and HAI-PMC was
      performed 6 months after. Metastatic foci of the liver had shrunk (90.9%), but
      solitary metastatic lung cancer was detected during HAI. As no other metastatic
      lesion was observed, partial resection of the liver and lung was performed as a
      second-look operation, 6 months after the initial operation. The woman continued
      venous infusion chemotherapy as an outpatient, and she survived for 6.5 years
      after the initial operation. This result suggests that strategic
      multidisciplinary treatment utilizing s-l hepatectomy after neoadjuvant
      chemotherapy can lead to better prognosis for colorectal cancer patients with
      hepatic metastases.

PMID- 17431356
TI  - [A case of effective regimen of tegafur and uracil (UFT)/leucovorin (LV) plus
      irinotecan (CPT-11) for advanced rectal carcinoma with severe pelvic infiltration
      to be performed curative resection].
AB  - A 72-year-old man was admitted to our hospital, complaining of severe diarrhea.
      Computed tomography, barium enema and colonoscopy revealed a cysto-rectal fistula
      and massive invasion to middle rectum and retroperitoneal space from the main
      tumor in the upper rectum. Because of obstruction of passage of stool, sigmoid
      colostomy was performed. Oral UFT/LV+CPT-11 were undertaken after surgery for 4
      cycles to remarkably reduce the tumor both clinically and on an outpatient basis.
      During this period, no side effect was detected, and a performance status (PS) of
      0 has been maintained. As the result, radical resection was performed 5 months
      after the first operation. The histological effect was judged to be grade 2.
      Furthermore, no recurrence was recognized after 16 months postoperatively.
      Therefore, oral administration of UFT/LV+CPT-11 was considered as effective
      neoadjuvant chemotherapy for advanced rectal carcinoma, and this also could be a
      promising regimen to maintain the quality of life (QOL) for patients in
      ambulatory therapy.

PMID- 17431357
TI  - [Two cases with have a complication in cardiac function during chemotherapy with
      trastuzumab].
AB  - The most fatal complication in trastuzumab therapy for breast cancer is cardiac
      disfunction. It can be classified two patterns, early onset type and late onset
      type. This complication often becomes severe, but it is reversible if appropriate
      steps are taken. In treating patients with trastuzumab, their cardiac function
      must be checked by echocardiogram every three months.

PMID- 17431358
TI  - [A case of relapsed acute myeloid leukemia with brain white matter lesions].
AB  - Lesions of the central nervous system (CNS) in acute myeloid leukemia (AML) have
      a wide range of causes. Apart from infection, virus, fungus and bacteria have to
      be excluded. Other causes including involvement of leukemia, toxic
      encephalopathies induced by chemotherapy and radiation therapy, and vascular
      lesions must be diagnosed differentially for advanced treatment or follow-up.
      While ultimate diagnosis rests on the collection of cerebrospinal fluid, it is
      not enough for essential diagnosis. Imaging techniques such as head MRI are
      powerful tools for diagnosis of intracranial organic lesions, especially in this
      setting involving leukemia, progressive multifocal leukoencephalopathy (PML) by
      JC virus infection and treatment-related disseminated necrotizing
      leukoencephalopathy. A 50-year-old man with AML, who relapsed three
      times,progressed to an acute consciousness disturbance and was complicated with
      multiple CNS lesions. He presented with a vesicle formation on his skin, which
      was pathologically diagnosed as virus infection 1 week after CNS lesions
      appeared. He was considered to have systemic herpes infection. In this case,
      considered judgment with multiple approaches would be needed for diagnosis in
      some cases of AML with the CNS infiltration shadow.

PMID- 17431359
TI  - [Primary gastric T-cell lymphoma with predominant bone marrow infiltration
      undergoing aggressive clinical course].
AB  - A 63-year-old man complained of high fever, epigastralgia, and severe cytopenia
      in June, 2005. Upper gastroduodenal endoscopy revealed a gastric tumor in the
      greater curvature of the body. Biopsy specimens showed the infiltration of medium
      sized abnormal cells. Bone marrow biopsy also indicated infiltration of the
      medium-sized abnormal cells. Immunophenotyping with abnormal cells was positive
      for CD 3, negative for CD 20 and cytokeratin. Serum investigation showed human T
      cell lymphotropic virus-1 (HTLV-1) antibody below 16 fold. The diagnosis was HTLV
      1 unassociated primary gastric T-cell lymphoma with bone marrow infiltration.
      After undergoing oral chemotherapy with VP-16 at 25 mg/day, combination
      chemotherapy was initiated with vincristine 2 mg/day and dexamethasone 48 mg/day.
      The man died with the aggressive clinical course after combination chemotherapy.

PMID- 17431360
TI  - [An inadvertent contraindicated combined use of newly prescribed TS-1 and unused
      doxifluridine].
AB  - A 77-year-old male patient who had been receiving doxifluridine (5'-DFUR) for
      about a year after surgery for rectal cancer, was newly prescribed TS-1, because
      tumor markers were elevated and abdominal ultrasonography documented liver
      metastasis. However, the patient took TS-1 concomitantly with 5'-DFUR, which is
      contraindicated to TS-1, and experienced a severe drug interaction. This
      inadvertent drug interaction was caused by a combination of the newly prescribed
      drug and the unused drug remaining at the patient's home. This type of medication
      error has not been reported previously. Health professionals should be aware of
      such drug interactions which may be caused by newly prescribed drugs plus unused
      drugs remaining in the patient's home. Furthermore, health professionals should
      instruct patients on the nature of drug interactions as well as explaining their
      diagnosis and treatment. Although the severity of such drug interaction may vary,
      health professionals must be alerted to such incidents, which could happen
      frequently.

PMID- 17431361
TI  - [A way of thinking of a MAB therapy for local/locally advanced prostate cancer:
      the theory and recent evaluation].
AB  - The MAB (Maximal Androgen Blockade) therapy is a treatment to exert maximal
      effects of hormone therapy, inhibiting androgen activity derived from both testes
      and adrenal gland that promotes proliferation of prostate cancer, being proposed
      by Dr. Labrie et al. in 1980s. For efficacy of the MAB therapy, a meta-analysis
      of randomized control studies with metastatic prostate cancer realized primarily
      in Europe and America showed the survival benefit of MAB therapy using
      nonsteroidal antiandrogen agent, which have placed it as a standard therapy for
      metastatic prostate cancer. However, it was suggested that the better effect of
      MAB therapy was expected in patients without distant metastasis rather than
      patients with metastatic prostate cancer, and it was noted that the time to
      progression (TTP) was significantly improved in patients of stage C in a
      randomized double-blind control study on bicalutamide+LH-RH agonist vs.
      placebo+LH-RH agonist conducted in Japan. In addition, the clinical study
      conducted by Dr. Labrie et al. suggested that the patients where the cure was
      expected did exist by continuing long-term MAB therapy against local prostate
      cancer. In this discussion meeting, inviting Dr. Labrie, the importance of MAB
      therapy among the hormone therapy against prostate cancer, the possibility of MAB
      therapy as a curative treatment against local/locally advanced prostate cancer
      and the ideal way of application of hormone therapy were discussed, and the
      significance was showed to conduct a most effective hormone therapy (MAB therapy)
      in earlier stage where the androgen sensitivity was noted.

PMID- 17431362
TI  - [Clinical administration of FOLFOX regimens for patients with unresectable
      advanced or recurrent colorectal cancer].
AB  - FOLFOX regimens were administered to 14 patients with unresectable advanced or
      recurrent colorectal cancer from 1 to 9 cycles (median 5 cycles). In our patient
      characteristics, 10 patients had previous chemotherapies, 3 patients showed
      performance status 3. The response rate was 21%, and median time to progression
      was 5.0 months. Frequency of grade 3/4 adverse effect was 57% in neutropenia, 36%
      in leucopenia, 36% in thrombocytopenia, and 7% in allergic reaction. Only 64%
      patients could complete the treatment, for these adverse events brought treatment
      failure at 3-6 cycles. Median relative dose-intensity was 80-90% during 1-4
      cycles, but about 50% after 5 cycles for these adverse events. No patient had
      grade 3 neurologic toxicity,because no one was administered over 10 cycles.
      FOLFOX regimens showed good anti-tumor effects but poor tolerability after 5-6
      cycles in our patients.

PMID- 17431366
TI  - [Single dose versus 5-day course of oral prulifloxacin in antimicrobial
      prophylaxis for transrectal prostate biopsy].
AB  - AIM: Prostate biopsy and histology are necessary studies for diagnosing prostate
      cancer. The rationale for antimicrobial prophylaxis in urologic, diagnostic and
      treatment procedures is given by the possible risk of bacterial contamination.
      Since oral administration is generally preferred and the most common pathogens
      are Gram-negative bacteria, the antimicrobials of choice are fluoroquinolones and
      amoxicillin/clavulanic acid. METHODS: The study sample was 432 consecutively
      enrolled males (age range 44-82 years) who underwent transrectal ultrasound
      guided prostate biopsy. The subjects were randomly assigned to 2 groups. One
      (210, 48.6%) received a single oral dose of prulifloxacin (600 mg) before the
      operation (group 1); the other (222, 51.4%) received a 5-day course of the
      antimicrobial. RESULTS: The most frequent events were bleeding (hematuria and
      hemospermia) (about 15%), which resolved spontaneously within several days.
      Fever, the chief symptom of infection, occurred in 4/432 (0.93%) and was equally
      distributed between the 2 groups (0.95% and 0.90% in groups 1 and 2,
      respectively). Patient compliance with antimicrobial prophylaxis was good to
      excellent. Histology of the prostate sample revealed carcinoma in 46.5%, and
      other prostate conditions in 53.5%: benign prostate hypertrophy, chronic
      prostatitis, high grade prostate intraepithelial neoplasia, and suspicious but
      not diagnostic atypia. CONCLUSIONS: In patients undergoing transrectal ultrasound
      guided prostate biopsy, antimicrobial prophylaxis with prulifloxacin, both in
      single shot and 5-day administration, was found to prevent infection, with good
      tolerability and acceptability by the patients.

PMID- 17431367
TI  - Systemic strategies for prostate cancer.
AB  - Systemic therapy beyond hormonal therapy for advanced prostate cancer includes
      chemotherapy, antiangiogenic therapy, signal transduction inhibitors,
      immunomodulatory therapy, and other experimental therapeutics. This review will
      discuss the state of systemic therapy for advanced prostate cancer in 2007, with
      an emphasis on therapy in the neoadjuvant, adjuvant, and metastatic setting. As
      chemotherapy gains greater acceptance in the urologic oncology community for use
      in men with hormone-refractory disease, evaluating the role of systemic therapy
      in earlier disease states is essential given the success in other solid tumors
      for advancing cure rates. Current randomized phase III trials worldwide are
      addressing these questions in each disease state, and are anticipated to change
      the landscape of prostate cancer management for years to come. In this
      discussion, we will emphasize those agents that are currently being evaluated in
      phase II and III trials, with an emphasis on those trials that are likely to
      impact the standard of care in the near future. The collection of tumor or
      surrogate tissue is emphasized to define biomarkers that may predict for
      sensitivity to these systemic therapies.

PMID- 17431368
TI  - Treatment options in locally advanced prostate cancer.
AB  - Even though the incidence has decreased, locally advanced prostate cancer remains
      a treatment challenge. Primary androgen ablation remains an option, but must be
      used judiciously as a high number of patients ultimately progress and die of
      prostate cancer. Unfortunately, while there is not good data that more aggressive
      treatment impacts significantly on survival, it does appear that some patients
      can be rendered free of disease. The failure rate with surgery alone has been
      high and androgen ablation has been used as a frequent adjunct. The randomized
      trials completed so far suggest that holding the androgen ablation for failure is
      as effective for survival. Randomized data with adjuvant radiation shows a
      significant decrease in biochemical and clinical failure, but a survival
      advantage is also not yet apparent. Historically, the results of primary
      radiation have been poor and have been only modestly improved with the addition
      of androgen ablation. In retrospective studies, favorable results have been
      achieved with dose escalation utilizing intensity modulated external beam
      radiation therapy or brachytherapy without the need for androgen ablation.

PMID- 17431369
TI  - Radical prostatectomy.
AB  - The management of prostate cancer is one of the core tasks for urologists today.
      Radical prostatectomy represents a valid therapeutic option for the curative
      treatment of localised prostate cancer. Urologists are on a continuous search for
      development of technical modifications and refinements, to reduce morbidity and
      ameliorate clinical and quality of life outcome. This review focuses on the
      clinical aspects of preoperative patient selection, the current trends of
      different surgical techniques and the indication of an adequate lymphadenectomy.

PMID- 17431370
TI  - Lymph node disease after radical prostatectomy.
AB  - Most patients with lymph node involvement at radical prostatectomy are destined
      to experience disease progression. Since the detection rate of lymph node
      metastases depends on the extension of lymphadenectomy, comparison between series
      may be biased and there is no generally accepted treatment approach. Although one
      small randomized study demonstrated a survival benefit for patients receiving
      immediate hormonal treatment compared with treatment onset at clinical
      progression, in patients with minimal lymph node involvement the benefit of
      immediate treatment is uncertain. It is possible that treatment onset at PSA
      relapse is sufficient in such cases thus sparing side effects and costs of
      hormonal treatment. The role of adjuvant radiotherapy is unclear in patients with
      lymph node involvement at radical prostatectomy. Since spread into the lymph
      nodes in most cases indicates systemic disease, local measures only are unlikely
      to cure those patients. Possibly, in select cases, adjuvant radiotherapy may
      improve local control and maintain quality of life, even if no survival benefit
      may be expected. Overall, there is a need to enroll patients with lymph node
      involvement at radical prostatectomy onto clinical studies to improve the body of
      knowledge on optimal management in these cases.

PMID- 17431371
TI  - Mediterranean diet, monounsaturated: saturated fat ratio and low prostate cancer
      risk. A myth or a reality?
AB  - Although the specific causes of prostate cancer initiation and progression are
      not yet known, evidence of a higher clinical incidence and mortality rates in
      Western societies than in Asian countries suggests that genetical, environmental
      and behavioural factors (such as diet) play an important role in the evolution of
      this disease. The nutritional etiology of prostate cancer has been evaluated in a
      large number of epidemiological studies and since traditional Asian diet is low
      in fatty components, it is not therefore surprising that dietary fat has been
      associated with prostate cancer risk in many of them. Experimental studies on the
      relationship between dietary patterns and increased prostate cancer risk
      supported further the idea that the risk of prostate cancer is increased as
      intake of fat rises. On the other hand, recent autopsy studies in Greece and
      Spain demonstrated that the incidence of histological prostate cancer in those
      Mediterranean Caucasian male populations is significantly lower than that of the
      other Caucasian males, while, epidemiological studies have reported a significant
      degree of adherence to the Mediterranean dietary pattern for Greek and Spanish
      males. Traditional Mediterranean dietary pattern has a relatively lower
      consumption of fat which consistency is characterized by a much higher
      monounsaturated:saturated fat ratio than in other places of the world. The
      purpose of the current article is to focus on the fatty components of the
      Mediterranean diet and elucidate their association with prostate cancer risk.

PMID- 17431372
TI  - Complications of radical cystectomy.
AB  - Radical cystectomy has become a standard and arguably the best definitive form of
      therapy for high-grade, invasive bladder cancer. Lower urinary tract
      reconstruction, particularly orthotopic diversion, has been a major component in
      enhancing the quality of life of patients requiring cystectomy. As with any major
      surgery, however, complications do arise. It is important for all surgeons to be
      familiar with the presentation, prevention and treatment of the major causes of
      morbidity and mortality associated with radical cystectomy and lower urinary
      tract reconstruction. The complications discussed are among the most common of
      the complications seen with cystectomy and urinary-intestinal diversion. There
      are, in fact, many others that may be encountered, as the published literature
      testifies, and a thorough understanding as to their presentation, prevention and
      treatment is equally essential for a successful patient outcome. Adherence to
      proper surgical technique, familiarization with recent data regarding the most
      successful treatment methods, and attention to detail in the perioperative period
      are crucial for minimizing complications in any surgical undertaking. Radical
      cystectomy with orthotopic neobladder as well as total pelvic exenteration and
      its modifications need to be considered among the treatment options for patients
      with muscle invasive bladder cancer or advanced pelvic malignancies. Recent
      advances in patient selection, surgical technique, and perioperative care have
      led to decreased morbidity. Despite this, these procedure remain complex with the
      potential for both short and long-term complications. There is abundant evidence
      that radical cystectomy for bladder malignancies and pelvic exenteration for
      primary rectal cancer and cervical cancer can lead to meaningful long-term
      survival; however, the prognosis after pelvic exenteration for recurrent rectal
      cancer is not as good. The recent introduction of combined chemoradiotherapy is
      likely to improve local recurrence rates and may translate into more durable long
      term survival. Pelvic exenteration continues to have an important role in the
      multimodality approach to patients with advanced pelvic malignancies. In
      conclusion, pelvic exenteration appears to be a safe and effective option for an
      experienced multi specialty surgical team in the treatment of complex locally
      advanced pelvic malignancy. The success of pelvic exenteration is highly
      dependent on good patient selection where an en bloc resection may result in
      prolonged disease-free survival and long term cure. In recent times the morbidity
      and mortality of this operation has decreased so that palliative exenteration has
      a role to help improve quality of life for this difficult group of patients.

PMID- 17431373
TI  - Laparoscopic partial nephrectomy: a review.
AB  - Surgical treatment of renal cell carcinoma has evolved dramatically in the last
      10 years. With the improvement of radiological imaging and minimally invasive
      nephron sparing techniques, more and more lesions can be managed
      laparoscopically. Stage migration to earlier lesions has followed the wider use
      of cross sectional tridimensional imaging. Open partial nephrectomy has been the
      benchmark to which laparoscopic partial nephrectomy (LPN) has been compared. In
      this review we focus on the available recent literature data on LPN and we
      outline the key surgical points.

PMID- 17431374
TI  - Radical cystectomy for urothelial cancer of the bladder: contemporary advances.
AB  - Radical cystectomy (RC) is an effective curative treatment for high grade and
      muscle invasive bladder cancer. Other treatments such as chemoradiation and
      transurethral resection of bladder tumor as monotherapy are generally not
      considered as effective as RC. RC is a major surgical procedure associated with
      significant morbidity and mortality. However, over the last decade significant
      advances have been made in different aspects of RC, including perioperative care,
      instrumentation and surgical techniques which has dramatically improved the
      outcome following RC. Different approaches including open, laparoscopic and
      robotic approaches are used to perform a RC. Devices such as vascular staplers
      and ligasure have decreased the blood loss and the need for transfusion. In this
      article, we review relevant literature and discuss various advances made in an
      attempt to improve outcome following RC.

PMID- 17431375
TI  - Bladder exstrophy variants.
AB  - In the literature it is possible to find many case reports of bladder exstrophy
      variants, although a thorough classification with all possible associated
      malformations is not yet available. On the basis of a rare case observed at their
      Department, the authors studied the embryology of these conditions and their
      associated malformations. The purpose of this study is to review the literature
      currently available and suggest a classification for bladder exstrophy variants.
      Despite the rarity of these variants, surgeons need to know all possible
      associated malformations in order to have the most complete and correct clinical
      picture of their patients.

PMID- 17431376
TI  - Severe methicillin-resistant Staphylococcus aureus community-acquired pneumonia
      associated with influenza--Louisiana and Georgia, December 2006-January 2007.
AB  - Staphylococcus aureus infection has been reported infrequently as a cause of
      community-acquired pneumonia (CAP) and typically has been associated with
      influenza virus infection or influenza-like illness (ILI). During the 2003-04
      influenza season, methicillin-resistant S. aureus (MRSA) gained attention as a
      cause of 15 cases of influenza-associated CAP. No formal surveillance has been
      conducted, and few additional cases of MRSA CAP were reported to CDC during the
      2004-05 and 2005-06 influenza seasons. However, in January 2007, CDC received
      reports of 10 cases of severe MRSA CAP, including six deaths, among previously
      healthy children and adults in Louisiana and Georgia during December 2006-January
      2007. These were the first reported cases of severe MRSA CAP during the 2006-07
      influenza season in the two states, and 10 was a higher number than expected for
      the 2-month period. A case of severe MRSA CAP was defined as pneumonia requiring
      hospitalization or resulting in the death of a patient from whom a specimen
      (i.e., sterile site or sputum sample) yielded MRSA when collected <48 hours after
      hospitalization or arrival at an emergency department (ED). Association with
      influenza was determined by either a positive result on a laboratory test or a
      diagnosis of ILI. This report describes three of the MRSA CAP cases as examples
      and summarizes all 10 of the reported cases. These cases underscore the need for
      health-care providers to be vigilant, especially during the influenza season, for
      severe cases of CAP that might be caused by MRSA.

PMID- 17431377
TI  - Nail-gun injuries treated in emergency departments--United States, 2001-2005.
AB  - Speed, ease of use, and ready availability have made pneumatic nail guns a common
      tool used in work settings such as residential construction and wood-product
      fabrication. In addition, the tools are now readily available to consumers,
      extending to the public what had been primarily a potential work-related hazard.
      To characterize nail-gun injuries in work and nonwork settings, patients with
      nail-gun injuries treated in U.S. hospital emergency departments (EDs) were
      studied by using the U.S. Consumer Product Safety Commission's (CPSC's) National
      Electronic Injury Surveillance System (NEISS) and the NEISS occupational injury
      supplement (NEISS-Work) maintained by CDC's National Institute for Occupational
      Safety and Health (NIOSH). This report describes the results of that analysis,
      which indicated that during the 5-year period 2001-2005, an average of
      approximately 37,000 patients with injuries related to nail-gun use were treated
      annually in EDs, with 40% of injuries (14,800) occurring among consumers. In
      addition, data on ED-treated injuries indicated that, in 2005, nail-gun injuries
      among consumers were approximately three times higher than in 1991 (4,200).
      Additional measures are needed to prevent nail-gun injuries among both workers
      and consumers.

PMID- 17431378
TI  - Update to CDC's sexually transmitted diseases treatment guidelines, 2006:
      fluoroquinolones no longer recommended for treatment of gonococcal infections.
AB  - In the United States, gonorrhea is the second most commonly reported notifiable
      disease, with 339,593 cases documented in 2005. Since 1993, fluoroquinolones
      (i.e., ciprofloxacin, ofloxacin, or levofloxacin) have been used frequently in
      the treatment of gonorrhea because of their high efficacy, ready availability,
      and convenience as a single-dose, oral therapy. However, prevalence of
      fluoroquinolone resistance in Neisseria gonorrhoeae has been increasing and is
      becoming widespread in the United States, necessitating changes in treatment
      regimens. Beginning in 2000, fluoroquinolones were no longer recommended for
      gonorrhea treatment in persons who acquired their infections in Asia or the
      Pacific Islands (including Hawaii); in 2002, this recommendation was extended to
      California. In 2004, CDC recommended that fluoroquinolones not be used in the
      United States to treat gonorrhea in men who have sex with men (MSM). This report,
      based on data from the Gonococcal Isolate Surveillance Project (GISP), summarizes
      data on fluoroquinolone-resistant N. gonorrhoeae (QRNG) in heterosexual males and
      in MSM throughout the United States. This report also updates CDC's Sexually
      Transmitted Diseases Treatment Guidelines, 2006 regarding the treatment of
      infections caused by N. gonorrhoeae. On the basis of the most recent evidence,
      CDC no longer recommends the use of fluoroquinolones for the treatment of
      gonococcal infections and associated conditions such as pelvic inflammatory
      disease (PID). Consequently, only one class of drugs, the cephalosporins, is
      still recommended and available for the treatment of gonorrhea.

PMID- 17431379
TI  - Preliminary FoodNet data on the incidence of infection with pathogens transmitted
      commonly through food--10 states, 2006.
AB  - Foodborne illnesses are a substantial health burden in the United States. The
      Foodborne Diseases Active Surveillance Network (FoodNet) of CDC's Emerging
      Infections Program collects data from 10 U.S. states regarding diseases caused by
      enteric pathogens transmitted commonly through food. FoodNet quantifies and
      monitors the incidence of these infections by conducting active, population-based
      surveillance for laboratory-confirmed illnesses. This report describes
      preliminary surveillance data for 2006 and compares them with baseline data from
      the period 1996-1998. Incidence of infections caused by Campylobacter, Listeria,
      Shigella, and Yersinia has declined since the baseline period. Incidence of
      infections caused by Shiga toxin-producing Escherichia coli O157 (STEC O157) and
      Salmonella, however, did not decrease significantly, and Vibrio infections have
      increased, indicating that further measures are needed to prevent foodborne
      illness and achieve national health objectives.

PMID- 17431380
TI  - Progress toward poliomyelitis eradication--Pakistan and Afghanistan, January 2006
      February 2007.
AB  - Of the four countries where wild poliovirus (WPV) transmission has never been
      interrupted, two are in the World Health Organization's (WHO) Eastern
      Mediterranean Region: Pakistan and Afghanistan. During January 2006-February
      2007, the number of reported WPV cases in both countries increased. In addition,
      an increase was observed in the number of affected districts; however, genetic
      diversity of the virus decreased, and regions of transmission remained limited.
      This report updates a previous report and describes polio cases and eradication
      activities in Pakistan and Afghanistan during January 2006-February 2007.
      Critical to the success of polio eradication will be high vaccination coverage
      among children in areas of frequent conflict along the border between these two
      countries.

PMID- 17431381
TI  - Expression of CD40 and CD40L on tumor cells: the role of their interaction and
      new approach to immunotherapy.
AB  - In the review the modern insights on the role of expression of CD40 and CD40L and
      the role of their interaction on tumor cells growth are analyzed. Information
      about the structure and biologic properties of these molecules and their
      interaction is presented. The question on the role of CD40/CD40L interaction is
      highlighted in two aspects--the possibility of tumor growth inhibition and its
      stimulation. According to the mentioned aspects, immunologic mechanisms providing
      tumor growth inhibition (the role of dendritic cells, macrophages, monocytes,
      cytotoxic T-lymphocytes, natural killer cells etc.), and also the possibility of
      apoptotic events are discussed. Possibility of tumor growth stimulation upon the
      influence of CD40/CD40L interaction that could occur in some cases is analyzed as
      well. The data of literature about new approaches to immunotherapy of cancer
      based on CD40/CD40L interactionare summarized.

PMID- 17431382
TI  - Growth inhibition and apoptosis induced by 2-phenoxymethyl-3H-quinazolin-4-one in
      HL-60 leukemia cells.
AB  - AIM: The aim of the study was to investigate anticancer activity of newly
      synthesized 2-phenoxymethyl-3H-quinazolin-4-one (PMQ). MATERIALS AND METHODS:
      Anticancer activity of PMQ was studied towards human HL-60 leukemia cells.
      Antiproliferative activity of PMQ was determined by direct counting of cells
      using trypan blue staining technique. Apoptosis and cell cycle profile changes
      were analysed using internucleosomal DNA fragmentation assay and flow cytometry.
      Activation of caspases and changes in glutathione level were monitored using
      colorimetric or luminiscent methods. RESULTS: PMQ induced concentration-dependent
      cytotoxicity in leukemia cells, with IC(50) of 10.8 +/- 0.9 microM. DNA flow
      cytometry analysis and DNA ladder formation assay indicated that PMQ actively
      induced apoptosis of cells accompanied by a block of cells in G(2)/M phase and a
      marked loss of cells in G(0)/G(1) and S phases. Additionally, the activities of
      caspase-3 and caspase-9 were increased significantly and a markedly increased
      level of oxidized glutahione was observed. Inhibition of glutahione synthesis
      using buthionine sulfoximine sensitized leukemia cells to PMQ, confirming the
      involvement of ROS in PMQ-induced apoptosis. CONCLUSION: The results of this
      study clearly demonstrate that PMQ is a promising anticancer drug showing
      cytostatic and apoptotic effects toward HL-60 leukemia cells mainly through
      mitochondrial/caspase-9 dependent pathway.

PMID- 17431383
TI  - Spontaneous premature condensation of chromosomes in normal and transformed
      mammal cells.
AB  - AIM: To study the relation between premature chromosome condensation and the
      ability of the cells to undergo malignant transformation. METHODS: Standard
      cytogenetic analysis of bone marrow cells and cultured normal and tumor cells has
      been used. RESULTS: Comparative analysis of the frequency of occurrence of the
      cells with premature chromosome condensation (PCC) (cell "arrest" at G2/M phase)
      in relation to dividing cells in the cultures of human immortalized cells of
      hematopoietic origin, human lung carcinoma A-549 cells, and in populations of
      bone marrow cells of BALB/c and C57BL/6 mice differing in predisposition for
      myeloma development has been performed. It has been revealed that in populations
      of bone marrow cells of C57BL/6 mice the relation of cells with PCC to dividing
      ones is 2-3-fold lower than in other studied cell populations. Immortalized and
      malignantly transformed human cell lines were characterized by high frequency of
      occurrence of cells with PCC. In the cells of A-549R subline characterized by
      suppressed malignant phenotype this index was lower than in parental A-549 cells.
      CONCLUSION: The obtained data point on possible relation between disturbed
      passing of "check point" by cells upon transition from G2 phase of cell cycle to
      mitosis and increased genetic heterogeneity of new cell generation associated
      with ability of cells to immortalization and malignant transformation.

PMID- 17431384
TI  - Combination of cyclooxygenase-2 inhibitor and doxorubicin increases the growth
      inhibition and apoptosis in human hepatocellular carcinoma cells.
AB  - Inhibition of cyclooxygenase (COX)-2 elicits therapeutic effects in solid tumors
      that are coupled with the inhibition of cell proliferation and induction of
      apoptosis in tumor cells. AIM: This study was designed to investigate the role of
      COX-2 inhibitor nimesulide in cell growth and apoptosis of the cultured human
      hepatocellular carcinoma HepG2 cells. METHODS: We performed the MTT assay, flow
      cytometric analysis and cell morphology study to evaluate growth inhibition and
      cell apoptosis upon the action of nimesulide alone or along with doxorubicin, a
      common agent for the treatment of human hepatocellular carcinoma. RESULTS: Our
      results showed that the treatment of HepG2 cells with more than 50 microM of
      nimesulide suppressed COX-2 enzyme activity because of reduced PGE(2) production,
      and then induced growth inhibition and cell apoptosis despite no alterations of
      COX-2 protein expression. Importantly, the combination of 50 microM or 100 microM
      of nimesulide and low concentrations (5 microM to 20 microM) of doxorubicin
      resulted in enhanced cell growth inhibition, apoptosis induction and reduced VEGF
      production. CONCLUSION: These data suggest synergistic and/or additive effects of
      COX-2 inhibitors and chemotherapeutic agents, and may provide the rational for
      clinical studies of COX-2 inhibitors on the treatment or chemoprevention of human
      hepatocellular carcinoma.

PMID- 17431385
TI  - Expression of membrane-anchored matrix metalloproteinase inhibitor reversion
      inducing cysteine rich protein with Kazal motifs in murine cell lines.
AB  - AIM: It has been demonstrated that the endogenous matrix metalloproteinases
      (MMPs) inhibitor reversion inducing cysteine rich protein with Kazal motifs
      (RECK) is a reliable prognostic marker for detecting several types of tumors.
      However, the RECK expressions in most of the normal and neoplastic tissues were
      extremely low, and to measure its expression is quite complicated. The purpose of
      the present study is to establish an easy method to quantify murine RECK mRNA
      expression for use in future experimental studies. Subsequently, in order to
      verify the reliability of the established quantification technique, we examined
      the change in RECK expression and gelatinase secretion in tumor cells when
      stimulated by the extracellular matrix. METHODS: Several murine tumor cells were
      used in the present study. The real-time polymerase chain reaction (PCR) method
      and measurement conditions for murine RECK mRNA were studied using these tumor
      cells. Gelatinase activities were also examined by gelatin zymography. RESULTS:
      Murine RECK mRNA expression was accurately quantified using real-time PCR. Among
      the tumor cells used in the study, osteosarcoma cells showed significantly higher
      RECK mRNA expression than the others. The RECK expression in the osteosarcoma
      cells was down-regulated by contact with matrigel-coated culture flasks due to
      increased secretion of gelatinases. CONCLUSION: The real-time PCR method employed
      in our study is useful to quantify RECK expression.

PMID- 17431386
TI  - The influence of psychoemotional status on metastasis of Lewis lung carcinoma and
      hepatocarcinoma-29 in mice of C57BL/6J and CBA/Lac strains.
AB  - AIM: To study the influence of psychoemotional status on the development of
      experimental lung metastases of strain-specific murine Lewis lung carcinoma in
      C57BL/6J mice and hepatocarcinoma-29 in CBA/Lac male mice. MATERIALS AND METHODS:
      Sensory contact model was used for generating animals with repeated experience of
      social victories or defeat in daily agonistic interactions. Tumor cells were
      injected into the tail vein after 20 days of aggressive confrontations and the
      number of metastases in the lung was calculated 16 days later. RESULTS: The
      experimental metastasis is shown to develop differently in mice with opposing
      social experience: the winners of both strains had significantly less metastases
      in the lung than the losers. CONCLUSION: The results obtained indicate that
      psychoemotional status affects Lewis lung carcinoma and hepatocarcinoma-29
      metastasis in male mice.

PMID- 17431387
TI  - Effect of silymarin on N-nitrosodiethylamine induced hepatocarcinogenesis in
      rats.
AB  - AIM: To study the effect of silymarin on the levels of tumor markers and MDA
      (malondialdehyde)-DNA adduct formation during N-nitrosodiethylamine induced
      hepatocellular carcinoma in male Wistar albino rats. METHODS: The levels of AFP,
      CEA and activities of liver marker enzymes in serum, MDA-DNA immunohistochemistry
      were done according to standard procedures in the control and experimental groups
      of rats. RESULTS: Hepatocellular carcinoma was evidenced from significant (p <
      0.05) increases of alpha-fetoprotein, carcinoembryonic antigen, aspartate
      aminotransferase, alanine aminotransferase, alkaline phosphatase, acid
      phosphatase, lactate dehydrogenase, gamma-glutamyltransferase and 5'-nucleotidase
      in serum and increased MDA-DNA adducts were also observed in the tissue sections
      of hepatocellular carcinoma. Silymarin treatment significantly attenuated the
      alteration of these markers and decreased the levels of MDA-DNA adduct formation.
      CONCLUSION: Silymarin could be developed as a promising chemotherapeutic adjuvant
      for the treatment of liver cancer.

PMID- 17431388
TI  - Synergistic therapeutic effect of arsenic trioxide and radiotherapy in BALB/C
      nude mice bearing nasopharyngeal carcinoma xenografts.
AB  - It has been shown that arsenic trioxide (ATO) induced apoptosis in human
      nasopharyngeal carcinoma cells and inhibited the growth of nasopharyngeal
      carcinoma xenografts (NPCX) in nude mice. AIM: The present study was designed to
      determine whether ATO at the non-toxic dose level could potentiate the
      therapeutic effectiveness of radiation therapy in nasopharyngeal carcinoma, using
      a BALB/C nude mouse xenograft model. METHODS: The mice bearing NPCX were treated
      with radiation alone (2, 4, and 6 Gy), ATO alone (4 mg/kg/day x 6 days), and ATO
      plus radiation at the same dosage levels. Time of tumor growth delay (defined as
      the time necessary for the tumor to grow four-fold of its initial volume after,
      compared with untreated tumors) and toxic effects were determined. RESULTS: The
      low dose ATO alone has no pronounced effects on tumor growth delay compared to
      untreated control. However, compared with radiation alone, the combined regimen
      delayed the tumor growth by 2-10 days and had no significant toxic effects such
      as the liver function damage. CONCLUSIONS: Combination of ATO at non-toxic dose
      level and radiation has synergistic effects on tumor growth inhibition in vivo
      and is well tolerated.

PMID- 17431389
TI  - Expression of p53, p21WAF1/CIP1, p16INK4A and Ki-67 proteins in serous ovarian
      tumors.
AB  - AIM: The analysis of p53, p21(WAF1/CIP1), p16(INK4A) and Ki-67 expression in
      serous ovarian carcinomas of different grade. MATERIALS AND METHODS: In total, 43
      ovarian adenocarcinomas and 8 non-altered ovarian epithelial tissues were
      immunohistochemically investigated for expression of Ki-67, p53, p21(WAF1/CIP1)
      and p16(INK4A). RESULTS: It has been shown that expression of Ki-67, p53,
      p21(WAF1/CIP1) and p16(INK4A) in non-altered ovarian epithelial tissue is absent.
      Serous ovarian carcinomas are characterized by high proliferative activity (PI Ki
      67 = 30.0 +/- 0.3%), p53 and p16(INK4A) overexpression (LI is 40.3 +/- 0.3% and
      31.1 +/- 0.6% respectively) and low expression of p21(WAF1/CIP1) (LI = 6.8 +/-
      0.3%). The association between expression of these markers and ovarian tumor
      grade was defined: the maximal level of Ki-67, p53 and p16/(INK4A) and minimal of
      p21(WAF1/CIP1) expression were observed in G3 tumors. So, low p21(WAF1/CIP1)
      expression (LI < 7.0%) combined with p16(INK4A) overexpression is considered to
      be the factor for a poor prognosis in serous ovarian cancer. CONCLUSIONS: The
      present study has indicated that biomolecular markers of cell proliferation along
      with traditional clinical and morphologic characteristics can be used for
      differential diagnostics of ovarian tumors.

PMID- 17431390
TI  - E-cadherin adhesion molecule and syndecan-1 expression in various thyroid
      pathologies.
AB  - Cadherins and syndecans are transmembrane glycoproteins implicated in cell-cell
      and cell-matrix adhesion. Impairment of cadherin and syndecan mediated adhesion
      is likely to constitute one of the main factors leading to the reduced cell-cell
      and cell-matrix adhesion characteristics of tumor cells and play a pivotal role
      in the acquisition of invasive and metastatic proprieties by neoplastic
      epithelial cells. AIM: To elucidate the role and alterations of syndecan-1
      expression in comparison with those of E-cadherin in normal and pathological
      thyroid glands (TG). METHODS: A total of 55 TG carcinomas, 40 TG adenomas, 40
      cases of hyperplastic TG disorders and 20 cases of normal TG autopsy samples,
      were evaluated by immunohistochemistry. The staining intensity, and localization
      of syndecan-1 and E-cadherin in sequential sections were examined, and semi
      quantified. RESULTS: Immunostaining of syndecan-1 and E-cadherin was strong in
      normal follicular TG epithelial cells, and located mainly in basolateral
      membrane. No significant change was seen in either molecule in hyperplastic TG
      disorders compared with TG adenomas. A significant reduction in expression of
      both syndecan-1 and E-cadherin was seen in well-differentiated TG carcinomas as
      compared with normal TG epithelium (p = 0.0001 and p = 0.032, respectively).
      Similarly, there was a significant reduction of both molecules expression in
      poorly differentiated and anaplastic TG carcinomas compared to well
      differentiated tumors (syndecan-1: p = 0.0037; and E-cadherin: p = 0.075).
      CONCLUSION: Decreased E-cadherin and syndecan-1 expression along with decreasing
      cellular differentiation may be involved in the complex mechanism of progression
      of TG pathology.

PMID- 17431391
TI  - The relation of serum anti-(GalNAc beta) and -para-Forssman disaccharide IgG
      levels to the progression and histological grading of gastrointestinal cancer.
AB  - Earlier we found two unusual IgG-antibody specificities to GalNAc beta and GalNAc
      beta1-3GalNAc beta (para-Forssman disaccharide, PFdi) carbohydrate ligands in
      human serum. The aim of the study was to evaluate whether elevated antibody
      levels are related to the progression of gastrointestinal cancer and the
      histopathological grading. METHODS: Specific IgG levels were tested in 159
      patients with gastric cancer, 88 patients with colorectal cancer and 96 blood
      donors by the ELISA using synthetic polyacrylaamide (PAA) conjugates, GalNAc beta
      PAA and PFdi-PAA. Biochemical and haematological analyses were performed using
      automatic equipment. RESULTS: The anti-PFdi IgG levels were significantly higher
      in patients with gastric and colorectal cancer than in donors: in stages II-IV, P
      = 0.0002 - 0.04 (U-test). The elevated anti-PFdi IgG level was associated with
      the advanced gastric cancer: in stages II, III, IV vs stage I (P = 0.004 - 0.06)
      and in case of the tumor size T2 + T3 vs T1 (stages I, II; P = 0.03). Differences
      in anti-GalNAc beta IgG level were insignificant. No relation between antibody
      levels and the regional and distant metastases of gastric or colorectal cancer
      was found. The lower anti-GalNAc beta IgG level was associated with lower
      differentiated carcinomas (P = 0.01 - 0.04). Prolonged postoperative changes in
      the levels of both antibodies during the follow-up were established. An elevation
      of both antibody levels in patients with gastrointestinal cancer was revealed
      after a surgical removal of G3-tumors (P = 0.003 - 0.01). The anti-PFdi IgG
      levels correlated with the levels of the C-reactive protein: r = 0.50, P = 0.003.
      The anti-GalNAc beta IgG levels correlated with the percentage of peripheral
      blood monocytes: r = 0.42, P = 0.002. CONCLUSION: The association of the anti
      PFdi IgG level with cancer progression suggests the implication of antibodies in
      the pathogenesis of gastrointestinal cancer. Further studies are required to
      identify natural targets of antibodies, their relation to other diseases,
      prognostic significance in cancer.

PMID- 17431392
TI  - TGF-beta1 and TNF-alpha after red blood cell transfusion in colorectal cancer
      patients.
AB  - Operations in patients with cancer are associated with blood transfusion to
      restore normal physiology. Blood transfusion can cause the immunomodulatory
      effect. There is lack of the literature data about influence of blood transfusion
      on the blood serum levels of cytokines TGF-beta and TNF-alpha, though these
      cytokines are important in neoplasia development. The aim of our study was to
      estimate changes in the concentration of cytokines TGF-beta1 and TNF-alpha in
      colorectal cancer patients' peripheral blood after surgery and allogenic red
      blood cell transfusion. METHODS: Venous blood of 64 patients with colorectal
      adenocarcinoma in stage III was tested before and after the surgery.
      Concentration of cytokines TGF-beta1 and TNF-alpha was quantitatively measured by
      ELISA. RESULTS: TGF-beta1 and TNF-alpha concentration significantly increased in
      the group of transfused colorectal cancer patients (before operation: TGF-beta
      10.1 +/- 1.3 ng/ml, TNF-alpha 20.9 +/- 1.7 pg/ml and after operation and RBC
      transfusion: TGF-beta 15.9 +/- 1.7 ng/ml; TNF-alpha 27.0 +/- 2.1 pg/ml).
      Statistical analysis has shown that serum levels of cytokines didn't change
      significantly after surgery in non-transfused patients group. CONCLUSION: These
      results indicate that levels of multipotent cytokines TGF-beta1 and TNF-alpha
      were elevated after red blood cell (RBC) transfusion in colorectal cancer
      patients.

PMID- 17431393
TI  - SMYD3 tandem repeats polymorphism is not associated with the occurrence and
      metastasis of hepatocellular carcinoma in a Chinese population.
AB  - A variable number of tandem repeats (VNTR) polymorphism in regulatory region of
      SMYD3 coding for histone methyltransferase has been shown to be associated with
      colorectal cancer, hepatocellular carcinoma (HCC), and breast cancer in Japanese
      population. Aim of the study is to investigate the potential association between
      the functional SMYD3 tandem repeats polymorphism and HCC in Chinese population.
      MATERIAL AND METHODS: The case-control study included 200 HCC patients and 261
      healthy controls. The VNTR polymorphism in the promoter of SMDY3 was genotyped by
      PCR and direct-sequencing analysis. Odds ratio and 95% confidence interval were
      used to estimate the association between the polymorphisms and risk of HCC.
      RESULTS: The allele frequencies for SMYD3 2 and 3 repeats were 15.71% and 84.29%
      among controls; and 12.75%, and 87.25% among cases (P = 0.22). The odds ratio for
      3/3 versus 2/2 and 2/3 genotypes was 1.30 (P = 0.18). The frequencies of 3
      alleles were not increased with HCC stage increased (trend test, P = 0.45).
      CONCLUSION: SMYD3 polymorphism is not associated with the occurrence and
      metastasis of HCC in Chinese population.

PMID- 17431394
TI  - The Golgi mitotic checkpoint is controlled by BARS-dependent fission of the Golgi
      ribbon into separate stacks in G2.
AB  - The Golgi ribbon is a complex structure of many stacks interconnected by tubules
      that undergo fragmentation during mitosis through a multistage process that
      allows correct Golgi inheritance. The fissioning protein CtBP1-S/BARS (BARS) is
      essential for this, and is itself required for mitotic entry: a block in Golgi
      fragmentation results in cell-cycle arrest in G2, defining the 'Golgi mitotic
      checkpoint'. Here, we clarify the precise stage of Golgi fragmentation required
      for mitotic entry and the role of BARS in this process. Thus, during G2, the
      Golgi ribbon is converted into isolated stacks by fission of interstack
      connecting tubules. This requires BARS and is sufficient for G2/M transition.
      Cells without a Golgi ribbon are independent of BARS for Golgi fragmentation and
      mitotic entrance. Remarkably, fibroblasts from BARS-knockout embryos have their
      Golgi complex divided into isolated stacks at all cell-cycle stages, bypassing
      the need for BARS for Golgi fragmentation. This identifies the precise stage of
      Golgi fragmentation and the role of BARS in the Golgi mitotic checkpoint, setting
      the stage for molecular analysis of this process.

PMID- 17431395
TI  - Endoplasmic reticulum quality control regulates the fate of transthyretin
      variants in the cell.
AB  - The secretion of transthyretin (TTR) variants contributes to the pathogenesis of
      amyloidosis because they form aggregates in the extracellular environment.
      However, the mechanism of how TTR variants pass the quality control system in the
      endoplasmic reticulum (ER) has not yet been elucidated. We investigated here the
      mechanism of how TTR passes ER monitoring. Monomeric mutation introduced in TTRs
      (M-TTRs) resulted in the ER retention of amyloidogenic M-TTRs but not non
      amyloidogenic M-TTRs. Retention of amyloidogenic M-TTRs induced the unfolded
      protein response and upregulated the expression of ER chaperones BiP and glucose
      regulated protein (GRP) 94. Additionally, we showed that the ER-retained
      amyloidogenic M-TTRs are subject to ER-associated degradation. On the other hand,
      the amyloidogenic TTR variants and non-amyloidogenic M-TTRs were secreted
      normally. These findings suggest that unlike for wild-type TTR, the ER quality
      control system may differentially regulate the fate of the TTR variants and their
      monomeric counterparts.

PMID- 17431396
TI  - XTsh3 is an essential enhancing factor of canonical Wnt signaling in Xenopus
      axial determination.
AB  - In Xenopus, an asymmetric distribution of Wnt activity that follows cortical
      rotation in the fertilized egg leads to the dorsal-ventral (DV) axis
      establishment. However, how a clear DV polarity develops from the initial
      difference in Wnt activity still remains elusive. We report here that the
      Teashirt-class Zn-finger factor XTsh3 plays an essential role in dorsal
      determination by enhancing canonical Wnt signaling. Knockdown of the XTsh3
      function causes ventralization in the Xenopus embryo. Both in vivo and in vitro
      studies show that XTsh3 substantially enhances Wnt signaling activity in a beta
      catenin-dependent manner. XTsh3 cooperatively promotes the formation of a
      secondary axis on the ventral side when combined with weak Wnt activity, whereas
      XTsh3 alone has little axis-inducing ability. Furthermore, Wnt1 requires XTsh3
      for its dorsalizing activity in vivo. Immunostaining and protein analyses
      indicate that XTsh3 is a nuclear protein that physically associates with beta
      catenin and efficiently increases the level of beta-catenin in the nucleus. We
      discuss the role of XTsh3 as an essential amplifying factor of canonical Wnt
      signaling in embryonic dorsal determination.

PMID- 17431397
TI  - beta-Subunit appendages promote 20S proteasome assembly by overcoming an Ump1
      dependent checkpoint.
AB  - Proteasomes are responsible for most intracellular protein degradation in
      eukaryotes. The 20S proteasome comprises a dyad-symmetric stack of four
      heptameric rings made from 14 distinct subunits. How it assembles is not
      understood. Most subunits in the central pair of beta-subunit rings are
      synthesized in precursor form. Normally, the beta5 (Doa3) propeptide is essential
      for yeast proteasome biogenesis, but overproduction of beta7 (Pre4) bypasses this
      requirement. Bypass depends on a unique beta7 extension, which contacts the
      opposing beta ring. The resulting proteasomes appear normal but assemble
      inefficiently, facilitating identification of assembly intermediates. Assembly
      occurs stepwise into precursor dimers, and intermediates contain the Ump1
      assembly factor and a novel complex, Pba1-Pba2. beta7 incorporation occurs late
      and is closely linked to the association of two half-proteasomes. We propose that
      dimerization is normally driven by the beta5 propeptide, an intramolecular
      chaperone, but beta7 addition overcomes an Ump1-dependent assembly checkpoint and
      stabilizes the precursor dimer.

PMID- 17431398
TI  - The neural EGF family member CALEB/NGC mediates dendritic tree and spine
      complexity.
AB  - The development of dendritic arborizations and spines is essential for neuronal
      information processing, and abnormal dendritic structures and/or alterations in
      spine morphology are consistent features of neurons in patients with mental
      retardation. We identify the neural EGF family member CALEB/NGC as a critical
      mediator of dendritic tree complexity and spine formation. Overexpression of
      CALEB/NGC enhances dendritic branching and increases the complexity of dendritic
      spines and filopodia. Genetic and functional inactivation of CALEB/NGC impairs
      dendritic arborization and spine formation. Genetic manipulations of individual
      neurons in an otherwise unaffected microenvironment in the intact mouse cortex by
      in utero electroporation confirm these results. The EGF-like domain of CALEB/NGC
      drives both dendritic branching and spine morphogenesis. The
      phosphatidylinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR)
      signaling pathway and protein kinase C (PKC) are important for CALEB/NGC-induced
      stimulation of dendritic branching. In contrast, CALEB/NGC-induced spine
      morphogenesis is independent of PI3K but depends on PKC. Thus, our findings
      reveal a novel switch of specificity in signaling leading to neuronal process
      differentiation in consecutive developmental events.

PMID- 17431399
TI  - A novel ISWI is involved in VSG expression site downregulation in African
      trypanosomes.
AB  - African trypanosomes show monoallelic expression of one of about 20 telomeric
      variant surface glycoprotein (VSG) gene-expression sites (ESs) while multiplying
      in the mammalian bloodstream. We screened for genes involved in ES silencing
      using flow cytometry and RNA interference (RNAi). We show that a novel member of
      the ISWI family of SWI2/SNF2-related chromatin-remodelling proteins (TbISWI) is
      involved in ES downregulation in Trypanosoma brucei. TbISWI has an atypical
      protein architecture for an ISWI, as it lacks characteristic SANT domains.
      Depletion of TbISWI by RNAi leads to 30-60-fold derepression of ESs in
      bloodstream-form T. brucei, and 10-17-fold derepression in insect form T. brucei.
      We show that although blocking synthesis of TbISWI leads to derepression of
      silent VSG ES promoters, this does not lead to fully processive transcription of
      silent ESs, or an increase in ES-activation rates. VSG ES activation in African
      trypanosomes therefore appears to be a multistep process, whereby an increase in
      transcription from a silent ES promoter is necessary but not sufficient for full
      ES activation.

PMID- 17431400
TI  - Embryonic and fetal beta-globin gene repression by the orphan nuclear receptors,
      TR2 and TR4.
AB  - The TR2 and TR4 orphan nuclear receptors comprise the DNA-binding core of direct
      repeat erythroid definitive, a protein complex that binds to direct repeat
      elements in the embryonic and fetal beta-type globin gene promoters. Silencing of
      both the embryonic and fetal beta-type globin genes is delayed in definitive
      erythroid cells of Tr2 and Tr4 null mutant mice, whereas in transgenic mice that
      express dominant-negative TR4 (dnTR4), human embryonic epsilon-globin is
      activated in primitive and definitive erythroid cells. In contrast, human fetal
      gamma-globin is activated by dnTR4 only in definitive, but not in primitive,
      erythroid cells, implicating TR2/TR4 as a stage-selective repressor. Forced
      expression of wild-type TR2 and TR4 leads to precocious repression of epsilon
      globin, but in contrast to induction of gamma-globin in definitive erythroid
      cells. These temporally specific, gene-selective alterations in epsilon- and
      gamma-globin gene expression by gain and loss of TR2/TR4 function provide the
      first genetic evidence for a role for these nuclear receptors in sequential, gene
      autonomous silencing of the epsilon- and gamma-globin genes during development,
      and suggest that their differential utilization controls stage-specific
      repression of the human epsilon- and gamma-globin genes.

PMID- 17431401
TI  - Cdk6 blocks myeloid differentiation by interfering with Runx1 DNA binding and
      Runx1-C/EBPalpha interaction.
AB  - Interactions between the cell cycle machinery and transcription factors play a
      central role in coordinating terminal differentiation and proliferation arrest.
      We here show that cyclin-dependent kinase 6 (Cdk6) is specifically expressed in
      proliferating hematopoietic progenitor cells, and that Cdk6 inhibits
      transcriptional activation by Runx1, but not C/EBPalpha or PU.1. Cdk6 inhibits
      Runx1 activity by binding to the runt domain of Runx1, interfering with Runx1 DNA
      binding and Runx1-C/EBPalpha interaction. Cdk6 expression increased myeloid
      progenitor proliferation, and inhibited myeloid lineage-specific gene expression
      and terminal differentiation in vitro and in vivo. These effects of Cdk6 did not
      require Cdk6 kinase activity. Cdk6-mediated inhibition of granulocytic
      differentiation could be reversed by excess Runx1, consistent with Runx1 being
      the major target for Cdk6. We propose that Cdk6 downregulation in myeloid
      progenitors releases Runx1 from Cdk6 inhibition, thereby allowing terminal
      differentiation. Since Runx transcription factors play central roles in
      hematopoietic, neuronal and osteogenic lineages, this novel, noncanonical Cdk6
      function may control terminal differentiation in multiple tissues and cell types.

PMID- 17431402
TI  - Cytokine-secreting herpes viral mutants effectively treat tumor in a murine
      metastatic colorectal liver model by oncolytic and T-cell-dependent mechanisms.
AB  - In this model of hepatic micrometastases, the antitumor efficacy and role of the
      T-cell and natural killer (NK) cell populations were studied for oncolytic herpes
      simplex virus type-1 (HSV-1) viral mutants containing the granulocyte-monocyte
      colony stimulating factor (GM-CSF (NV1034)) or interluken-12 (IL-12 (NV1042))
      cytokine genes. These were compared to saline and control virus (NV1023) in vitro
      and in vivo. HSV-1 mutants were assessed for cytotoxicity, replication and
      cytokine expression in CT-26 cells. A syngeneic micrometastatic liver model was
      then established in naive and immune cell-depleted animals to assess the
      antitumor efficacy of these viruses. In vitro cytotoxicity and viral replication
      were similar for each virus, resulting in greater than 80 and 98% cytotoxicity at
      multiplicity of infection of 1 and 10, respectively. Peak viral titers were 25-
      to 50-fold higher than initial titer and were not significantly different between
      viruses. In vivo, all three viruses reduced metastases relative to control, but
      cytokine-secreting viruses did so with greater efficacy compared to NV1023. This
      effect was abrogated by T-cell depletion, but not NK-cell depletion. Single-agent
      therapy with oncolytic viral agents containing GM-CSF or IL-12 is effective in a
      murine model of liver metastases and likely involves direct viral oncolysis and
      actions of specific immune effector cells.

PMID- 17431403
TI  - Adenoviral-mediated PTEN expression radiosensitizes non-small cell lung cancer
      cells by suppressing DNA repair capacity.
AB  - Expression of the PTEN tumor suppressor gene is abnormal in many human cancers.
      Loss of PTEN expression leads to the activation of downstream signaling pathways
      that have been associated with resistance to radiation. In non-small cell lung
      carcinoma (NSCLC), suppressed expression of PTEN is frequently due to methylation
      of its promoter region. In this study, we tested whether gene transfer of wild
      type PTEN into an NSCLC cell line with a known methylated PTEN promoter, H1299,
      would increase its sensitivity to ionizing radiation. Pretreating H1299 cells
      with an adenoviral-mediated PTEN (Ad-PTEN)-expressing vector sensitized H1299
      cells to radiation. To determine the mechanism responsible for
      radiosensitization, we first examined radiation-induced apoptosis, which was
      enhanced but did not correlate with radiosensitizing effect of Ad-PTEN.
      Therefore, we next examined the ability of Ad-PTEN to modulate the repair of
      radiation-induced DNA double-strand breaks (DSBs) using the detection of repair
      foci positive for gamma-H2AX, a protein that becomes evident at the sites of each
      DSB and that can be visualized by immunofluorescent staining. Compared with
      controls, the repair of radiation-induced DSBs was retarded in H1299 cells
      pretreated with Ad-PTEN, consistent with the radiosensitizing effect of the
      vector. We conclude that signal transduction pathways residing primarily in the
      cytoplasm may intersect with DNA damage and repair pathways in the nucleus to
      modulate cellular responses to radiation. Elucidating the mechanisms responsible
      for this intersection may lead to novel strategies for improving therapy for
      cancers with defective PTEN.

PMID- 17431404
TI  - The cortical organization of speech processing.
AB  - Despite decades of research, the functional neuroanatomy of speech processing has
      been difficult to characterize. A major impediment to progress may have been the
      failure to consider task effects when mapping speech-related processing systems.
      We outline a dual-stream model of speech processing that remedies this situation.
      In this model, a ventral stream processes speech signals for comprehension, and a
      dorsal stream maps acoustic speech signals to frontal lobe articulatory networks.
      The model assumes that the ventral stream is largely bilaterally organized-
      although there are important computational differences between the left- and
      right-hemisphere systems--and that the dorsal stream is strongly left-hemisphere
      dominant.

PMID- 17431406
TI  - Development trends for monoclonal antibody cancer therapeutics.
AB  - Monoclonal antibodies are now established as a key therapeutic modality for a
      range of diseases. Owing to the ability of these agents to selectively target
      tumour cells, cancer has been a major focus of development programmes for
      monoclonal antibodies so far. Here, we overview trends in the clinical
      development and regulatory approval of monoclonal antibodies for cancer since
      1980, with the aim of informing future research and development for this class of
      therapeutics.

PMID- 17431407
TI  - Systems biology meets chromatin function. Workshop on Nuclear Organization.

PMID- 17431408
TI  - Hedgehogs: la dolce vita. Workshop on Hedgehog-Gli Signaling in Cancer and Stem
      Cells.

PMID- 17431409
TI  - The Drosophila mitotic inhibitor Fruhstart specifically binds to the hydrophobic
      patch of cyclins.
AB  - The hydrophobic patch of cyclins interacts with cyclin-dependent kinase (Cdk)
      substrates and p27-type Cdk inhibitors. Although this interaction is assumed to
      contribute to the specificity of different Cdk-Cyclin complexes, its role in
      specific steps of the cell cycle has not been demonstrated. Here, we show that in
      Drosophila the mitotic inhibitor Fruhstart (Frs) binds specifically and with high
      affinity to the hydrophobic patch of cyclins. In contrast to p27-type Cdk
      inhibitors, Frs does not form a stable interaction with the catalytic centre of
      Cdk and allows phosphorylation of generic model substrates, such as histone H1.
      Consistent with a 2.5 times stronger binding to CycA than to CycE in vitro,
      ectopic expression of frs induces endocycles, in a manner similar to that
      reported previously for downregulation of CycA or Cdk1. We propose that binding
      of Frs to cyclins blocks the hydrophobic patch to interfere with Cdk1 substrate
      recognition.

PMID- 17431410
TI  - Biliary intraepithelial neoplasia: an international interobserver agreement study
      and proposal for diagnostic criteria.
AB  - Cholangiocarcinoma of the intrahepatic and extrahepatic bile ducts develops
      through a multistep histopathologic sequence. Premalignant or non-invasive
      neoplastic lesions of bile ducts have been historically called biliary dysplasia
      or atypical biliary epithelium. To this date, no standard terminology or
      classification system has been offered for these lesions. In 2005, a conceptual
      framework and diagnostic criteria for biliary intraepithelial neoplasia (BilIN)
      were proposed using the livers of patients with hepatolithiasis. We report herein
      an international interobserver agreement study on the diagnosis of biliary non
      invasive neoplastic lesions with the goal to obtain a consensus on the
      terminology and grading. Seventeen pathologists from the United States, Europe
      and Asia participated in this study. They shared a digital file containing
      histological pictures of 30 foci of non-invasive neoplastic lesions selected from
      the biliary system of patients suffering from primary sclerosing cholangitis,
      choledochal cyst or hepatolithiasis. In the criteria, we proposed in 2005, BilIN
      was classified into three categories based on the degree of atypia: BilIN-1,
      BilIN-2 and BilIN-3. In this study, consensus was reached for the terminology of
      BilIN and the three-grade classification system. Interobserver agreement on the
      diagnosis was moderate (kappa-value=0.45). On the basis of the suggestions and
      opinions obtained from the 17 participants, the original criteria for BilIN were
      revised. We now propose a new consensus classification of BilIN that may assist
      in allowing a more uniform terminology for the diagnosis of biliary non-invasive
      neoplastic lesions. This classification should help to advance clinical and
      research applications.

PMID- 17431411
TI  - Significance of C4d staining in ABO-identical/compatible liver transplantation.
AB  - Complement degradation product C4d has become an important marker of humoral or
      antibody-mediated rejection in renal and heart allograft biopsies. Although there
      have been several reports on the detection of C4d in liver allografts, the
      significance of C4d in liver transplantation and its relationship with humoral
      rejection are still not clear. We investigated the frequency and pattern of C4d
      staining in liver allograft biopsies with reference to preoperative lymphocyte
      crossmatch tests, which detect donor-reactive lymphocyte antibody. Survival rates
      at 5 years were 77% for crossmatch-negative patients and 53% for crossmatch
      positive patients (P=0.009). In crossmatch-negative patients, reproducible
      positive staining was obtained in 28 of 86 (33%) biopsies taken within 90 days
      after transplantation and 33 of 96 (34%) biopsies 90 days or after
      transplantation. Most C4d staining was observed in the portal areas, and no clear
      correlation was observed between C4d positivity and histological diagnosis. In
      crossmatch-positive patients, 9 of 11 (82%) biopsies showed positivity for C4d.
      C4d stained perivenular areas as well as portal areas. Histology of crossmatch
      positive patients included acute rejection and cholangitis, but did not include
      periportal changes that were seen in humoral rejection in ABO-incompatible liver
      transplantation. In summary, focal C4d deposition was seen in various types of
      liver allograft injury and had little clinical impact on crossmatch-negative
      patients, but extensive C4d staining in crossmatch-positive patients may be
      associated with humoral rejection and poor graft survival.

PMID- 17431412
TI  - Detection of COL1A1-PDGFB fusion transcripts and PDGFB/PDGFRB mRNA expression in
      dermatofibrosarcoma protuberans.
AB  - Fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived
      growth factor beta chain (PDGFB) gene has been described in dermatofibrosarcoma
      protuberans. The abnormal fusion transcripts probably cause PDGFB and its
      receptor (platelet-derived growth factor receptor beta, PDGFRB) autocrine
      stimulation and cell proliferation, which are responsible for the development of
      dermatofibrosarcoma protuberans. A reverse transcription-polymerase chain
      reaction assay was performed to detect the COL1A1-PDGFB fusion transcripts in 57
      samples. In addition, the PDGFB gene amplification and PDGFB/PDGFRB mRNA levels
      were quantified by a real-time PCR system for the samples in which the fusion
      transcripts had been successfully detected. The fusion transcripts were detected
      in 42 of 57 samples. Various exons of the COL1A1 gene were fused in frame with
      the PDGFB gene; exons 7 and 25 were found to be slightly more frequently involved
      than the other exons. The PDGFB gene amplification levels varied from 0.6 to 8.3
      (mean 2.4) in 42 tumor samples and from 0.4 to 3.0 (mean 1.2) in 20 adjacent
      normal tissue samples. In the 20 paired samples, the PDGFB gene amplification in
      the tumor was significantly higher than that in the normal tissue. The presence
      of PDGFB and PDGFRB mRNAs was demonstrated in 26 and 21 of 26 cases,
      respectively. The PDGFB and PDGFRB mRNA expression levels showed a good
      correlation (r=0.76, P<0.0001). These results indicate that the fusion protein,
      which is processed by the COL1A1-PDGFB transcripts, can serve as a functional
      ligand for PDGFRB.

PMID- 17431413
TI  - A micropapillary pattern is predictive of a poor prognosis in lung
      adenocarcinoma, and reduced surfactant apoprotein A expression in the
      micropapillary pattern is an excellent indicator of a poor prognosis.
AB  - A micropapillary pattern is defined as papillary tufts without a fibrovascular
      core and is known to be a factor that indicates a poor prognosis in numerous
      cancers. However, their role in lung adenocarcinoma has not been investigated
      widely. In 185 cases of small-size lung adenocarcinoma (< or =3 cm), cases with a
      micropapillary pattern ratio of more than 1% (analyzed by NIH image) were defined
      as micropapillary pattern positive. Correlations between the micropapillary
      pattern and clinicopathological factors were investigated and immunohistochemical
      expression of mucin and various antigens was examined in regions with and without
      micropapillary patterns. Micropapillary pattern-positive tumors (micropapillary
      pattern ratio > or =1%) were observed in 11.4% of cases (21/185) and the
      micropapillary pattern ratio correlated with TNM stage (P=0.0002), lymphatic
      invasion (P=0.0002) and lymph node metastasis (P=0.03). Disease-free interval
      (P<0.0002) and survival (P=0.027) were significantly shorter for micropapillary
      pattern-positive patients, and micropapillary pattern-positive stage IA cases
      also had a significantly shorter disease-free interval (P<0.0001). MUC1 was
      expressed strongly across the surface of the micropapillary structure, whereas
      MUC4 tended to show lower expression in the micropapillary pattern. It was
      noteworthy that the disease-free interval in patients with high surfactant
      apoprotein A expression was significantly better than in patients with low
      surfactant apoprotein A expression (P=0.03), and no recurrence or death occurred
      in patients with high surfactant apoprotein A expression. Our results show that
      the micropapillary pattern ratio correlates with lymphatic invasion and lymph
      node metastasis, and that a high micropapillary pattern ratio leads to a poor
      prognosis. High MUC1 expression on the surface is an important characteristic of
      a micropapillary pattern, and reduced surfactant apoprotein A expression in the
      micropapillary pattern may be an excellent indicator for poor prognosis in small
      size lung adenocarcinoma.

PMID- 17431414
TI  - Rare expression of BSAP (PAX-5) in mature T-cell lymphomas.
AB  - Lineage determination in lymphomas is based on the assessment of lineage-specific
      markers, such as the B-cell-specific activator protein of the paired box family
      (BSAP, PAX-5) for the B-cell lineage. BSAP is thought to be expressed exclusively
      in B cells from the pro-B- to the mature B-cell stage and then silenced in plasma
      cells. BSAP has oncogenic potential and experimental evidence shows that the T
      cell lineage is prone to this effect. Herein, we report on a BSAP-positive
      peripheral T-cell lymphoma with monoclonal T-cell receptor gamma-gene
      rearrangement. To assess the relative frequency of BSAP expression in mature T
      cell lymphomas, we constructed and examined a tissue microarray consisting of 43
      angioimmunoblastic T-cell lymphomas and peripheral T-cell lymphomas and detected
      no additional BSAP-positive cases. To conclude, BSAP can probably contribute to T
      cell lymphomagenesis not only in vitro, but also in vivo. It is rarely expressed
      in peripheral T-cell lymphoma, thus its detection on lymphoid malignancies cannot
      be considered definitively lineage specific.

PMID- 17431415
TI  - Non-incidental coamplification of Myc and ERBB2, and Myc and EGFR, in gastric
      adenocarcinomas.
AB  - This study was conducted to assess the frequencies of protein overexpression and
      gene amplification of Myc and to identify the mechanisms of Myc gene
      amplification, especially with regards to its possible coamplification with ERBB2
      or EGFR in gastric adenocarcinomas. By immunohistochemical analysis of a total of
      300 formalin-fixed and paraffin-embedded gastric adenocarcinomas, the nuclear
      overexpression of MYC was found in 47 tumors (16%). A fluorescence in situ
      hybridization (FISH) analysis revealed that nine (19%) of the 47 tumors with
      protein overexpression had cancer cells with high levels of Myc amplification,
      whereas only seven (6%) of the 122 tumors without protein overexpression showed
      high-level Myc gene amplification. Such Myc amplification was significantly
      correlated with positive nuclear protein overexpression. The coamplification of
      ERBB2 or EGFR with Myc that was found in six and four cases, respectively, is
      believed to be non-incidental because those frequencies were significantly higher
      than the individual frequencies observed for the total examined cases (ERBB2: 7%;
      EGFR: 4%). The high levels of gene amplification of these three genes, as
      visualized by FISH, could be broadly classified into two typical types, namely,
      'multiple scattered signals' and 'large clustered signals'. Using two-color FISH,
      the coexistence of coamplified Myc and ERBB2, or Myc and EGFR, within single
      nuclei in various combinations of amplification types and copy numbers, could be
      ascertained in all nine cases, including one in which the synchronous 'multiple
      scattered type' coamplification of Myc and ERBB2 was observed. In three tumors,
      coamplification of ERBB2 and EGFR was found; however, ERBB2- and EGFR-amplified
      cell populations were separate and mutually exclusive. We propose that the non
      incidental coamplification of Myc and either ERBB2 or EGFR occurred through
      translocation and subsequent rearrangement.

PMID- 17431416
TI  - Calcium signalling and pancreatic cell death: apoptosis or necrosis?
AB  - Secretagogues, such as cholecystokinin and acetylcholine, utilise a variety of
      second messengers (inositol trisphosphate, cADPR and nicotinic acid adenine
      dinucleotide phosphate) to induce specific oscillatory patterns of calcium
      (Ca(2+)) signals in pancreatic acinar cells. These are tightly controlled in a
      spatiotemporal manner, and are coupled to mitochondrial metabolism necessary to
      fuel secretion. When Ca(2+) homeostasis is disrupted by known precipitants of
      acute pancreatitis, for example, hyperstimulation or non-oxidative ethanol
      metabolites, Ca(2+) stores (endoplasmic reticulum and acidic pool) become
      depleted and sustained cytosolic [Ca(2+)] elevations replace transient signals,
      leading to severe consequences. Sustained mitochondrial depolarisation, possibly
      via opening of the mitochondrial permeability transition pore (MPTP), elicits
      cellular ATP depletion that paralyses energy-dependent Ca(2+) pumps causing
      cytosolic Ca(2+) overload, while digestive enzymes are activated prematurely
      within the cell; Ca(2+)-dependent cellular necrosis ensues. However, when stress
      to the acinar cell is milder, for example, by application of the oxidant
      menadione, release of Ca(2+) from stores leads to oscillatory global waves,
      associated with partial mitochondrial depolarisation and transient MPTP opening;
      apoptotic cell death is promoted via the intrinsic pathway, when associated with
      generation of reactive oxygen species. Apoptosis, induced by menadione or bile
      acids, is potentiated by inhibition of an endogenous detoxifying enzyme
      NAD(P)H:quinone oxidoreductase 1 (NQO1), suggesting its importance as a defence
      mechanism that may influence cell fate.

PMID- 17431417
TI  - Atg5 and Bcl-2 provide novel insights into the interplay between apoptosis and
      autophagy.

PMID- 17431418
TI  - Cell death modalities: classification and pathophysiological implications.

PMID- 17431419
TI  - Mitochondrial Ca2+ as a key regulator of cell life and death.
AB  - Mitochondrial Ca(2+) homeostasis is today at the center of wide interest in the
      scientific community because of its role both in the modulation of numerous
      physiological responses and because of its involvement in cell death. In this
      review, we briefly summarize a few basic features of mitochondrial Ca(2+)
      handling in vitro and within living cells, and its involvement in the modulation
      of Ca(2+)-dependent signaling. We then discuss the role of mitochondrial Ca(2+)
      in the control of apoptotic death, focusing in particular on the effects of pro-
      and anti-apoptotic proteins of the Bcl-2 family. Finally, the potential
      involvement of Ca(2+) and mitochondria in the development of two diseases,
      Ullrich muscular dystrophy and familial Alzheimer's disease, is briefly
      discussed.

PMID- 17431420
TI  - Cardiac repair by stem cells.

PMID- 17431421
TI  - Glia: the fulcrum of brain diseases.
AB  - Neuroglia represented by astrocytes, oligodendrocytes and microglial cells
      provide for numerous vital functions. Glial cells shape the micro-architecture of
      the brain matter; they are involved in information transfer by virtue of numerous
      plasmalemmal receptors and channels; they receive synaptic inputs; they are able
      to release 'glio'transmitters and produce long-range information exchange;
      finally they act as pluripotent neural precursors and some of them can even act
      as stem cells, which provide for adult neurogenesis. Recent advances in gliology
      emphasised the role of glia in the progression and handling of the insults to the
      nervous system. The brain pathology, is, to a very great extent, a pathology of
      glia, which, when falling to function properly, determines the degree of neuronal
      death, the outcome and the scale of neurological deficit. Glial cells are central
      in providing for brain homeostasis. As a result glia appears as a brain warden,
      and as such it is intrinsically endowed with two opposite features: it protects
      the nervous tissue as long as it can, but it also can rapidly assume the guise of
      a natural killer, trying to eliminate and seal the damaged area, to save the
      whole at the expense of the part.

PMID- 17431422
TI  - The SPRY domain of Pyrin, mutated in familial Mediterranean fever patients,
      interacts with inflammasome components and inhibits proIL-1beta processing.
AB  - The autoinflammatory disorders Muckle-Wells syndrome, familial cold urtecaria and
      chronic infantile neurological cutaneous and articular syndrome are associated
      with mutations in the NALP3 (Cryopyrin) gene, which is the central platform of
      the proinflammatory caspase-1 activating complex, named the inflammasome. In
      patients with another autoinflammatory disorder, familial Mediterranean fever
      (FMF), mutations in the SPRY domain of the Pyrin protein are frequently found.
      Recent evidence suggests that Pyrin associates with ASC, an inflammasome
      component, via its Pyrin domain, thereby halting the inflammatory response. This
      interaction, however, does not explain the effects of mutations of the SPRY
      domain found in FMF patients. Here we show that the Pyrin SPRY domain not only
      interacts with NALP3, but also with caspase-1 and its substrate pro
      interleukin(IL)-1beta. Whereas a Pyrin knockdown results in increased caspase-1
      activation and IL-1beta secretion, overexpression of the SPRY domain alone blocks
      these processes. Thus Pyrin binds to several inflammasome components thereby
      modulating their activity.

PMID- 17431423
TI  - Matrix metalloproteinase-9 in glutamate-dependent adult brain function and
      dysfunction.

PMID- 17431424
TI  - S-Nitrosylation and uncompetitive/fast off-rate (UFO) drug therapy in
      neurodegenerative disorders of protein misfolding.
AB  - Although activation of glutamate receptors is essential for normal brain
      function, excessive activity leads to a form of neurotoxicity known as
      excitotoxicity. Key mediators of excitotoxic damage include overactivation of N
      methyl-D-aspartate (NMDA) receptors, resulting in excessive Ca(2+) influx with
      production of free radicals and other injurious pathways. Overproduction of free
      radical nitric oxide (NO) contributes to acute and chronic neurodegenerative
      disorders. NO can react with cysteine thiol groups to form S-nitrosothiols and
      thus change protein function. S-nitrosylation can result in neuroprotective or
      neurodestructive consequences depending on the protein involved. Many
      neurodegenerative diseases manifest conformational changes in proteins that
      result in misfolding and aggregation. Our recent studies have linked nitrosative
      stress to protein misfolding and neuronal cell death. Molecular chaperones - such
      as protein-disulfide isomerase, glucose-regulated protein 78, and heat-shock
      proteins - can provide neuroprotection by facilitating proper protein folding.
      Here, we review the effect of S-nitrosylation on protein function under
      excitotoxic conditions, and present evidence that NO contributes to degenerative
      conditions by S-nitrosylating-specific chaperones that would otherwise prevent
      accumulation of misfolded proteins and neuronal cell death. In contrast, we also
      review therapeutics that can abrogate excitotoxic damage by preventing excessive
      NMDA receptor activity, in part via S-nitrosylation of this receptor to curtail
      excessive activity.

PMID- 17431425
TI  - Role of cardiolipin in cytochrome c release from mitochondria.

PMID- 17431426
TI  - Cleavage and degradation of Claspin during apoptosis by caspases and the
      proteasome.
AB  - Apoptosis plays a crucial role in development and tissue homeostasis. Some key
      survival pathways, such as DNA damage checkpoints and DNA repair, have been
      described to be inactivated during apoptosis. Here, we describe the processing of
      the human checkpoint protein Claspin during apoptosis. We observed cleavage of
      Claspin into multiple fragments in vivo. In vitro cleavage with caspases 3 and 7
      of various fragments of the protein, revealed cut sites near the N- and C-termini
      of the protein. Using mass spectrometry, we identified a novel caspase cleavage
      site in Claspin at Asp25. Importantly, in addition to cleavage by caspases, we
      observed a proteasome-dependent degradation of Claspin under apoptotic
      conditions, resulting in a reduction of the levels of both full-length Claspin
      and its cleavage products. This degradation was not dependent upon the DSGxxS
      phosphodegron motif required for SCF(beta-TrCP)-mediated ubiquitination of
      Claspin. Finally, downregulation of Claspin protein levels by short interfering
      RNA resulted in an increase in apoptotic induction both in the presence and
      absence of DNA damage. We conclude that Claspin has antiapoptotic activity and is
      degraded by two different pathways during apoptosis. The resulting disappearance
      of Claspin from the cells further promotes apoptosis.

PMID- 17431427
TI  - Antagonism of p66shc by melanoma inhibitory activity.
AB  - The p66shc protein governs oxidant stress and mammalian lifespan. Here, we
      identify melanoma inhibitory activity (MIA), a protein secreted by melanoma
      cells, as a novel binding partner and antagonist of p66shc. The N-terminal
      collagen homology-2 (CH2) domain of p66shc binds to the Src Homology-3 (SH3)-like
      domain of MIA in vitro. In cells, ectopically expressed MIA and p66shc colocalize
      and co-precipitate. MIA also co-precipitates with the CH2 domain of p66shc in
      vivo. MIA expression in vivo suppresses p66shc-stimulated increase in endogenous
      hydrogen peroxide (H(2)O(2)), and inhibits basal and H(2)O(2)-induced
      phosphorylation of p66shc on serine 36 and H(2)O(2)-induced death. In human
      melanoma cells expressing MIA, endogenous MIA and p66shc co-precipitate.
      Downregulation of MIA in melanoma cells increases basal and ultraviolet radiation
      (UVR)-induced phosphorylation of p66shc on serine 36, augments endogenous
      H(2)O(2) levels, and increases their susceptibility to UVR-induced death. These
      findings show that MIA binds to p66shc, and suggest that this interaction
      antagonizes phosphorylation and function of p66shc.

PMID- 17431428
TI  - Regulation of mitochondrial mRNA stability by RNase L is translation-dependent
      and controls IFNalpha-induced apoptosis.
AB  - Interferons (IFNs) inhibit the growth of many different cell types by altering
      the expression of specific genes. IFNs activities are partly mediated by the 2'
      5' oligoadenylates-RNase L RNA decay pathway. RNase L is an endoribonuclease
      requiring activation by 2'-5' oligoadenylates to cleave single-stranded RNA.
      Here, we present evidence that degradation of mitochondrial mRNA by RNase L leads
      to cytochrome c release and caspase 3 activation during IFNalpha-induced
      apoptosis. We identify and characterize the mitochondrial translation initiation
      factor (IF2mt) as a new partner of RNase L. Moreover, we show that specific
      inhibition of mitochondrial translation with chloramphenicol inhibits the
      IFNalpha-induced degradation of mitochondrial mRNA by RNase L. Finally, we
      demonstrate that overexpression of IF2mt in human H9 cells stabilizes
      mitochondrial mRNA, inhibits apoptosis induced by IFNalpha and partially reverses
      IFNalpha-cell growth inhibition. On the basis of our results, we propose a model
      describing how RNase L regulates mitochondrial mRNA stability through its
      interaction with IF2mt.

PMID- 17431429
TI  - [Vaccination against Hepatitis B: 20 years later].
AB  - More than 20 years have elapsed since 1984, when vaccination against Hepatitis B
      began, first with a plasma-derived vaccine and later a recombinant DNA-derived
      vaccine, and during this period important changes have taken place in several
      aspects of this disease: the acute and chronic infection rates, the mortality of
      fulminant Hepatitis B in infants and the incidence of hepatocellular carcinoma
      have been effectively reduced by approximately 25%. Vaccination during childhood
      has produced adequate protection for up to 20 years later. The appearance of
      Hepatitis B surface gene mutants in DNA HBV positive children has been confirmed,
      gradually increasing from 7.8% before vaccination to 23.1% 15 years later. To
      date, there is no evidence that those viruses are disrupting the efforts to
      control Hepatitis B through immunization programmes. A good immune response
      through the vaccination of premature infants with low birth weight has been
      implemented by delaying the start of the vaccination programme to between 7 and
      30 days after birth. It has also been proposed that there is an increased risk of
      non-response to the Hepatitis B vaccine among elderly people. Finally, it has
      been proven that the Hepatitis B vaccine is one of the safest Vaccines available
      in the world.

PMID- 17431432
TI  - [The high fermentative capacity of colonic bacteria in the origin of flatulence
      and its sensibility to bismuth subsalicylate].
AB  - Using a previously described technique, "in vitro" determinations were carried
      out for faecal fermentation (FF): basal faecal fermentation (BFF), i.e, only with
      faeces, with faeces and lactulose (LFF) and with faeces, lactulose and bismuth
      subsalicylate (BiLFF) in 34 patients with flatulence. The media+d.s. of the
      difference between the LFFand BFF levels (LFF-BFF) in patients with flatulence
      was significant and markedly higher than the respective media +d.s. in 30 normal
      control patients previously studied (9.1+4.7 vs. 3.9+3.2 ml gas/24 hrs;
      p<0.000001 respectively). And, although FF was reduced by adding bismuth
      salicylate in only 24% (70.6%) of the patients with flatulence but not in the
      remaining 10 (29.4%), in total the media+d.s. of the differences between the
      levels BiLFF and BFF (BiLFFBFF) was significantly lower that the media+d.s. of
      the differences between the LFF and BFF levels (LFF-BFF) (6.0+4.2 vs 9.1+4.7 ml
      gas/24 hrs; p<0.01 respectively). These results confirm that: 1) The fermentative
      capacity of the colonic bacteriae is most likely to be abnormally intense in
      peoples with flatulence and 2) Bismuth subsalicylate can be useful in the control
      of excessive colonic fermentation and flatulence; they raise, furthermore, the
      interesting possibility that we may have found the way to predict when the use of
      bismuth subsalicylate could be effective in the treatment of a patient with
      flatulence.

PMID- 17431433
TI  - [Prognosis factors in acute hepatic insufficiency].
AB  - INTRODUCTION: Acute Hepatic Insufficiency (AHI) is a rare syndrome but has a high
      mortality rate. The purpose of this study was to determine the clinico
      epidemiological characteristics of AHI. MATERIALS AND METHODS: Open study,
      prospective, descriptive of patients diagnosed with AHI in the Liver Unit of the
      Edgardo Rebagliati Martins State Hospital (HNERM) from February 1999 until
      January 2003. RESULTS: Fifteen (15) cases were studied. The average age was 63
      (30-81), the M-F ratio was 2/1. The diagnosis was viral Hepatitis B (53.3%),
      toxic idiosyncratic reactions (20%), undetermined (20%) and Hepatitis A (6.7%).
      At the time of diagnosis 80% had Grade I encephalopathy and 20% Grade III
      encephalopathy; 13.3% did not have ascites and 86.7% had mild-moderate ascites;
      53.3% had a history of chronic illness (diabetes, chronic renal insufficiency,
      cardiopathy and others). Average laboratory values were: albumin 2.5 gr./dl,
      bilirubin 25.9 mg/dl, prothrombin time 29 and Factor V 40.7%. The most frequent
      complications were sepsis and cerebral oedema. Global mortality was 80%. The
      average survival time was 16.6 days. CONCLUSIONS: In most cases the patients were
      over 60 years of age. The main cause of AHI was viral Hepatitis B, a disease
      which can be prevented with active immunisation. Infection and cerebral oedema
      were common causes of death. AHI, although rare, is a rapidly degenerative and
      fatal condition.

PMID- 17431434
TI  - [Hyperendemic and mesoendemic zones of Fasciola infection surrounding urban Lima
      : an emerging disease?].
AB  - INTRODUCTION: The infection caused by F. hepatica is endemic in Peru with an
      increasing number of endemic areas, the reporting of them is essential to know
      the impact of the infection in the population. OBJECTIVE: To report the
      prevalence rate of fascioliasis in areas where it had not been detected human
      cases previously. MATERIAL AND METHODS: Three districts in Lima department were
      studied; La Chaqui, province of Canta; San Lorenzo of Quinti and San Miguel of
      Sangallaya, province of Huarochiri. It included children and young adults (less
      than 25 years old). One stool sample by person was collected and processed by
      means of the Rapid Sedimentation Technique described by Lumbreras. RESULTS:
      Overall, the prevalence rate in the three districts was 8.6% (n=291); 3.9%
      (n=102) in La Chaqui, 26.9% (n=27) in San Miguel of Sangallaya, and 8.6% (n=163)
      in San Lorenzo of Quinti. CONCLUSION: F. hepatica infection is a Health Public
      problem in populations surrounding Lima city. Therefore, control and prevention
      measurements, besides being addressed to authochtonus people, should also take
      into account high-risk groups such as frequent travelers to endemic areas and
      people with dietetic programs based on raw vegetables.

PMID- 17431435
TI  - [Hyponatremia as a possible mortality factor in cirrhotic patients hospitalised
      in the Guillermo Almenara Irigoyen State Hospital, 2003- 2005].
AB  - INTRODUCTION: In the decompensated hepatic cirrhosis the development of
      complications such as bleeding in the digestive tracts, encephalopathy, ascites
      and spontaneous bacterial peritonitis is well-known; another important
      complication is the development of dilutional hyponatremia resulting from severe
      circulatory and renal dysfunction and which different papers have linked to a
      higher mortality rate. The main purpose of the present study is to determine if
      hyponatremia is an independent prognosis factor in the mortality of cirrhotic
      patients. MATERIAL AND METHODS: A retrospective study of cases and controls was
      carried out. Cirrhotic patients hospitalized in the Guillermo Almenara Irigoyen
      Hospital from January 2003 to June 2005 were evaluated; the patients who died
      with MELD10 were defined as cirrhotic; the controls were living cirrhotic
      patients with MELD<or=10. They further were classified according to the presence
      or not of hyponatremia. For each group the clinical and analytical
      characteristics, the extent of the hepatic dysfunction and the seric levels of
      sodium were established. In order to compare the groups the student t test was
      used; to determine if hyponatremia was an independent prognosis factor of
      mortality the raw OR and the adjusted OR were calculated, the latter through a
      model of logistic regression. RESULTS: Forty (40) test patients and 56 controls
      were used. Hyponatremia was found in 28.13% of the total of cirrhotic patients
      and in 50% of the deceased cirrhotic patients. Upon comparing the groups of alive
      and deceased cirrhotic patients a significant difference was found in terms of
      the age (p=0.0013), Child (p=0.000), MELD (p=0.004), bilirubin (p=0.009), albumin
      (p=0.000), creatinine (p=0.019) and seric sodium (p=0.002). The independent
      mortality risk factors were the presence of hyponatremia (adjusted OR); 4.83, IC
      95% 1.42 16.49), the previous SAE (adjusted OR: 3.42, IC - 95% 1.13- 10.33) and
      the presence of associated infection (adjusted OR: 4.83, IC - 95% 1.55- 15.03).
      CONCLUSIONS: The prevalence of hyponatremia in hospitalized cirrhotic patients
      with MELD>or=10 was 28.13%. Hyponatremia, previous ascites and linked infection
      are independent prognosis factors for mortality of cirrhotic patients.

PMID- 17431436
TI  - ["Epidemiological profile of chronic hepatitis C virus patients and his early
      virological response to pegylated interferon plus ribavirin therapy.
      Gastroenterology Service, HNCASE EsSALUD Arequipa"].
AB  - The present descriptive, retrospective and longitudinal study was designed to
      determine the epidemic profile of patients infected by hepatitis C virus and
      chronic hepatitis, as well as to describe the eligibility criteria for treatment
      with pegilated interferon plus ribavirina and its early virological answer to the
      treatment. We studied 20 patients treated at Gastroenterology Service of Carlos
      Seguin Escobedo Hospital of EsSalud between 2004 and 2006. The diagnosis of HVC
      infection was confirmed by detection of viral RNA with PCR, and the viral load by
      counting number of RNA copies. The eligibility criteria for antiviral treatment
      were determined, and also the METAVIR score to determine hepatic fibrosis. After
      12 weeks of treatment the patients with eligibility criteria and received
      treatment were evaluated, and the effectivity of treatment was evaluated with a
      new determination of viral load. There were more female (15; 75%) than male
      patients (5; 25%), with ages between 50 and 59 years. The more frequent risk
      antecedent was blood transfusion (45%), surgery (35%), and traffic accident
      (10%). The hematological, hepatic, renal and hormonal parameters were in normal
      range; and the viral load at the moment of diagnosis was of 580 thousand copies
      mean (between 4100 to 2 millions copies). The most frequent viral genotypes were
      1a and 1b. Up to 40% of patients did not fulfilled eligibility criteria for
      treatment. Nine of 12 patients with eligibility criteria received treatment
      (75%), 6 of them were evaluated for early virologic response and of them 100,0%
      had an early virologic response with decrease of post-therapeutic viral load in
      all but one cases until non-detectable levels. In conclusion our study described
      the profile of patients infected by HCV with chronic hepatitis in
      gastroenterology ward of our hospital, and it has been determined that is
      suggestive that antiviral treatment is highly effective in patients with
      eligibility criteria for treatment, related to early virologic response.

PMID- 17431437
TI  - [Viral Hepatitis A over imposed on chronic hepatic damage due to tamoxifen:
      report of a case].
AB  - A case of Hepatitis A is reported in a patient prescribed tamoxifen after surgery
      for breast cancer and taking tamoxifen 20 mg/day for two and a half years.
      Documented is the indirect development of Hepatitis A and tamoxifen-induced
      hepatic damage.

PMID- 17431438
TI  - [Reappearance of severe typhoid forms following a case of massive
      gastrointestinal haemorrhaging].
AB  - A case of a patient is reported who was admitted with massive intestinal
      haemorrhaging after 10 days of medical discomfort, characterized by persistent
      fever, headache and abdominal pain. The patient did not respond to medical
      treatment: antibiotics, blood transfusions and fluid replacement and required
      emergency surgical intervention. Intestinal resection with primary anastomosis
      was performed, controlling the bleeding. Following the testing of blood cultures
      and histopathological study infection by the S. tiphy bacteria was recorded by
      testing. In Latin America this strain of typhoid fever was common until the
      beginning of the 90's, before the cholera epidemic and has rarely been seen in
      the past 15 years.

PMID- 17431439
TI  - [Choledochal cyst in pregnancy and puerperium: report on two cases and review of
      literature].
AB  - A choledochal cyst is a cystic dilation of the intrahepatic or extrahepatic
      biliary tract. According to the most accepted theory, it is caused by an
      anomalous pancreatobiliary junction. The most important complications are
      cholangiocarcinoma, lithiasis, and pancreatitis. Current therapy is surgical
      resection. Only 20% to 30% of cases are diagnosed in adult life. Two cases of
      choledochal cysts are reported in female adult patients, one of them in late
      pregnancy and the other in puerperium. Diagnosis of choledochal cyst in pregnancy
      and puerperium is an uncommon event, entailing particular considerations
      regarding symptoms and treatment.

PMID- 17431440
TI  - [Surgical treatment of giant serous cystadenoma of pancreas: report of two
      cases].
AB  - INTRODUCTION: The cystic tumor of the pancreas is a relatively uncommon entity.
      There are different types of pancreatic cystic tumors and they all exhibit
      different degrees of malignancy. These tumors represent 1% of all primary
      pancreatic tumors and only 15% of the cystic lesions. The serous cystadenomas
      (SCA) are mostly benign lesions with an average size of 4 cm; nevertheless, in
      some rare cases these are giant lesions, generally larger than 15 cm. Sometimes
      these tumors produce a symptomatology caused by the compression of neighboring
      structures, therefore they are generally operable. MATERIAL AND METHOD: During
      the period from June 2004 to June 2005, the 3A II unit of the Edgardo Rebagliati
      Martins Hospital operated on two cases of giant serous cystadenomas of the
      pancreas, one located in the tail of the pancreas and the other in the head of
      the pancreas, with an average size of 16 cm. DISCUSSION: The giant SCAs of the
      pancreas are rarely seen lesions that, according to different authors, are
      usually larger than 10 to 15 cm. in diameter. These lesions do not represent a
      diagnosis problem and are generally operable since they produce a symptomatology
      by compression. The surgical resection can be complicated due to their large size
      and to the considerable neovascularization.

PMID- 17431441
TI  - [Localization of pancreatic insulinoma with ultrasonography laparoscopy].
AB  - The case of a 51-year-old woman with a clinical history of hipoglicemia caused by
      a presumed pancreatic insulinoma is reported. Laboratory tests pointed out for a
      insulinoma, but imaginologic studies could not locate the tumor. Under this
      circumstances, the patient was laparoscopically approached. By means of the
      ultrasonography device the tumor was located at the uncinate process of the
      pancreas and, eventually treated by laparoscopic enucleation.

PMID- 17431442
TI  - Operational Characteristics of a 14-W 140-GHz Gyrotron for Dynamic Nuclear
      Polarization.
AB  - The operating characteristics of a 140-GHz 14-W long pulse gyrotron are
      presented. The device is being used in dynamic nuclear polarization enhanced
      nuclear magnetic resonance (DNP/NMR) spectroscopy experiments. The gyrotron
      yields 14 W peak power at 139.65 GHz from the TE(0,3) operating mode using a 12.3
      kV 25-mA electron beam. Additionally, up to 12 W peak has been observed in the
      TE(2,3) mode at 136.90 GHz. A series of mode converters transform the TE(0,3)
      operating mode to the TE(1,1) mode. Experimental results are compared with
      nonlinear simulations and show reasonable agreement. The millimeter-wave output
      beam was imaged in a single shot using a pyroelectric camera. The mode patterns
      matched reasonably well to theory for both the TE(0,1) mode and the TE(1,1) mode.
      Repeatable mode patterns were obtained at intervals ranging from 0.8 s apart to
      11 min apart at the output of the final mode converter.

PMID- 17431443
TI  - CoDE: Community Diabetes Education for uninsured Mexican Americans.
AB  - Low-cost diabetes education programs that target Mexican Americans are essential
      to reduce the observed health disparities in this population. A culturally
      appropriate intervention was developed as the centerpiece of the Community
      Diabetes Education (CoDE) program. This article describes the structure, patient
      acceptance, and costs of this one-to-one educational model delivered in 7 patient
      contact hours by a community health worker over 12 months in a community clinic
      serving the uninsured. A total of 162 patients-predominantly female, Spanish
      speaking Mexican American patients with type 2 diabetes of mean duration of 6.5
      years-enrolled in the program, and a dropout rate of 22% was observed during the
      12-month period. Preliminary analysis indicated that program capacity was 120
      patients per month, and the annual direct medical expenditure per CoDE
      participant was $461. The hemoglobin A(1c) was significantly reduced in patients
      who participated in the program for 12 months. Sustainable, low-cost, community
      based programs like CoDE and long-term patient participation will help reduce the
      burden of diabetes in the underserved Hispanic population.

PMID- 17431444
TI  - Achieving American Diabetes Association goals in HIV-seropositive patients with
      diabetes mellitus.
AB  - This retrospective study examined whether the goals set forth by the American
      Diabetes Association were being attained in an HIV specialty clinic run by
      internal medicine physicians. The charts of 40 HIV patients with diabetes were
      reviewed. Patients were divided into two groups: those who had seen a clinical
      pharmacist for medication adherence counseling (n = 20) and those who had not (n
      = 20). Overall, less than 50% of patients were achieving goals of therapy for
      hemoglobin A(1c), cholesterol, triglycerides, and blood pressure. Only 5% were
      documented as receiving aspirin therapy. The medication adherence counseling was
      not a significant factor in the results. Clinicians need to be aware of the
      concomitant disease states that HIV patients have and to treat those disease
      states to the standard of care set forward.

PMID- 17431445
TI  - Thoracic outlet syndrome: a 50-year experience at Baylor University Medical
      Center.
AB  - During the past 5 decades, the recognition and management of thoracic outlet
      syndrome (TOS) have evolved. This article elucidates these changes and
      improvements in the diagnosis and management of TOS at Baylor University Medical
      Center. The most remarkable change over the past 50 years is the use of nerve
      conduction velocity to diagnose and monitor patients with nerve compression.
      Recognition that procedures such as breast implantation and median sternotomy may
      produce TOS has been revealing. Prompt thrombolysis followed by surgical venous
      decompression for Paget-Schroetter syndrome has markedly improved results
      compared with the conservative anticoagulation approach; thrombolysis and prompt
      first rib resection is the optimal treatment for most patients with Paget
      Schroetter syndrome. Complete first rib extirpation at the initial procedure
      markedly reduces the incidence of recurrent neurologic symptoms or the need for a
      second procedure. Chest pain or pseudoangina can be caused by TOS. Dorsal
      sympathectomy is helpful for patients with sympathetic maintained pain syndrome
      or causalgia and patients with recurrent TOS symptoms who need a second
      procedure.

PMID- 17431446
TI  - Invited commentary.

PMID- 17431447
TI  - Advances in the treatment of superficial venous insufficiency of the lower
      extremities.
AB  - Minimally invasive techniques for ablation of incompetent saphenous veins using
      either radiofrequency or laser energy sources have gained acceptance and are
      being widely applied today. Tumescent local anesthesia provides protection to
      tissues surrounding the treated veins and allows the procedures to be done on
      conscious patients. Results thus far compare favorably with surgical stripping
      procedures. Efficacy rates and complication rates support these techniques, and
      patient satisfaction appears high. Microphlebectomy, also minimally invasive, has
      advantages over direct incisional excision of varicosities. Foam sclerosant
      injection therapy has been used extensively in Europe and is proving useful in
      treating refluxing pelvic veins and recurrent varicosities.

PMID- 17431448
TI  - Hospitalists and anesthesiologists as perioperative physicians: Are their roles
      complementary?
AB  - In recent years, there has been an increased emphasis on the role of
      anesthesiologists as perioperative physicians. However, a new group of physicians
      called hospitalists has emerged and established a role as perioperative
      physicians. Most hospitalists have specialized in internal medicine and its
      subspecialties. We reviewed American medical literature over the last 13 years on
      the roles of anesthesiologists and hospitalists as perioperative physicians.
      Results showed that the concept of the anesthesiologist as the perioperative
      physician is strongly supported by the American Board of Anesthesiology and the
      leaders of the specialty. However, most anesthesiologists limit their practice to
      intraoperative care and immediate acute postoperative care in the postanesthesia
      care unit. The hospitalists may fill a different role by caring for patients in
      the preoperative and sometimes in the postoperative period, allowing the surgeon
      to focus on surgery. These roles of the anesthesiologists and the hospitalists as
      perioperative physicians may be complementary. We conclude that if
      anesthesiologists and hospitalists work together as peri-operative physicians,
      with each specialty bringing its expertise to the care of the perioperative
      patient, care is likely to improve. It is necessary to be proactive and identify
      areas of future cooperation and collaboration.

PMID- 17431449
TI  - Notta's nodules and trigger digits.

PMID- 17431450
TI  - Combined cardiac and liver transplantation for the treatment of familial
      amyloidosis.

PMID- 17431451
TI  - Kikuchi-Fujimoto disease (histiocytic necrotizing lymphadenitis): report of a
      case with other autoimmune manifestations.
AB  - Kikuchi-Fujimoto disease (KFD), or histiocytic necrotizing lymphadenitis, is a
      benign and self-limited disease that mainly affects young women. Patients present
      with localized lymphadenopathy, fever, and leukopenia in up to half of the cases.
      KFD can occur in association with systemic lupus erythematosus. We present the
      case of a patient with KFD and systemic lupus erythematosus, as well as relapsing
      polychondritis. This patient had persistently low C4 complement levels, so she
      was evaluated for a genetic defect in complement production and was found to have
      two "null" C4 alleles. We believe that this may have contributed to the
      development of her diseases.

PMID- 17431452
TI  - Reader comments: Acute right ventricular myocardial infarction: a very specific
      entity.

PMID- 17431453
TI  - Clinical transformation and Mr. Lincoln's "t-mails".

PMID- 17431454
TI  - Hypertrophic and atrophic scars.

PMID- 17431455
TI  - Pseudoventricular flutter.

PMID- 17431456
TI  - Posaconazole (Noxafil): a new triazole antifungal agent.
AB  - Posaconazole is the newest triazole antifungal agent. It is structurally related
      to itraconazole and has activity against Candida species, Aspergillus species,
      Cryptococcus neoformans, the zygomycetes, and other filamentous fungi.
      Randomized, double-blind trials have shown posaconazole to be at least as
      efficacious as fluconazole for the prevention of invasive fungal infections in
      immunocompromised patients. It has also shown promising results in the treatment
      of various fungal infections refractory to other antifungal therapy. The dose of
      posaconazole is 200 mg orally three times daily for the prevention of invasive
      fungal infections and 800 mg daily in two to four divided doses for the treatment
      of invasive fungal infections refractory to other antifungal treatment. All
      posaconazole doses should be given with food or a nutritional supplement to
      enhance absorption. The most common adverse effects reported with posaconazole
      therapy were fever, diarrhea, nausea, vomiting, and headache. Instances of
      elevated liver enzyme levels, hyperbilirubinemia, and hepatocellular damage were
      also noted in clinical trials, and these laboratory values should be monitored
      during treatment with posaconazole.

PMID- 17431457
TI  - Facts and ideas from anywhere.

PMID- 17431460
TI  - Pfiesteria in estuarine waters: the question of health risks.

PMID- 17431461
TI  - Warfare: rallying around the environmental flag.

PMID- 17431463
TI  - Secondhand smoke: displaced enthusiasm?

PMID- 17431464
TI  - Policy: chrysotile on ice.

PMID- 17431465
TI  - Environmental justice: the Tuskegee legacy project.

PMID- 17431467
TI  - Centered on breast cancer.

PMID- 17431469
TI  - Beyond the bench: research helps clean up a water supply.

PMID- 17431470
TI  - Secondhand suspicions: breast cancer and passive smoking.

PMID- 17431471
TI  - Environment: California out in front.

PMID- 17431472
TI  - More human, more humane: a new approach for testing airborne pollutants.
AB  - People not only inhale airborne contaminants but also absorb them through the
      skin. Both routes can set off localized toxic reactions or damage internal organs
      such as the liver, kidney, and brain. Conventional tests of the toxicity of gases
      and vapors, in which laboratory animals are exposed to lethal or sub-lethal doses
      of chemicals, have been criticized as expensive, unethical, inhumane, and time
      consuming. Now researchers at the University of New South Wales (UNSW) in Sydney,
      Australia, have developed an animal-free alternative that uses human cells to
      test the effects of exposure to airborne toxicants.

PMID- 17431477
TI  - Lead in paint: three decades later and still a hazard for African children?
AB  - BACKGROUND: Surveys undertaken in South Africa have shown that a large proportion
      of children are exposed to lead from a variety of sources. OBJECTIVES: The
      overall objective of this work was to examine, through a series of small-scale
      investigations, the role of lead-based paint in the blood lead distribution of
      South African children. DISCUSSION: We suggest that the African public health
      community strengthen their efforts to prevent lead poisoning in African children
      through a holistic approach that includes the promulgation and enforcement of
      appropriate legislation as well as research to identify further sources of
      exposure to lead.

PMID- 17431478
TI  - Separation of risks and benefits of seafood intake.
AB  - BACKGROUND: Fish and seafood provide important nutrients but may also contain
      toxic contaminants, such as methylmercury. Advisories against pollutants may
      therefore conflict with dietary recommendations. In resolving this conundrum,
      most epidemiologic studies provide little guidance because they address either
      nutrient benefits or mercury toxicity, not both. OBJECTIVES: Impact on the same
      health outcomes by two exposures originating from the same food source provides a
      classical example of confounding. To explore the extent of this bias, we applied
      structural equation modeling to data from a prospective study of developmental
      methylmercury neurotoxicity in the Faroe Islands. RESULTS: Adjustment for the
      benefits conferred by maternal fish intake during pregnancy resulted in an
      increased effect of the prenatal methylmercury exposure, as compared with the
      unadjusted results. The dietary questionnaire response is likely to be an
      imprecise proxy for the transfer of seafood nutrients to the fetus, and this
      imprecision may bias the confounder-adjusted mercury effect estimate. We explored
      the magnitude of this bias in sensitivity analysis assuming a range of error
      variances. At realistic imprecision levels, mercury-associated deficits increased
      by up to 2-fold when compared with the unadjusted effects. CONCLUSIONS: These
      results suggest that uncontrolled confounding from a beneficial parameter, and
      imprecision of this confounder, may cause substantial underestimation of the
      effects of a toxic exposure. The adverse effects of methylmercury exposure from
      fish and seafood are therefore likely to be underestimated by unadjusted results
      from observational studies, and the extent of this bias will be study dependent.

PMID- 17431479
TI  - Skin exposure to isocyanates: reasons for concern.
AB  - OBJECTIVE: Isocyanates (di- and poly-), important chemicals used worldwide to
      produce polyurethane products, are a leading cause of occupational asthma.
      Respiratory exposures have been reduced through improved hygiene controls and the
      use of less-volatile isocyanates. Yet isocyanate asthma continues to occur, not
      uncommonly in settings with minimal inhalation exposure but opportunity for skin
      exposure. In this review we evaluate the potential role of skin exposure in the
      development of isocyanate asthma. DATA SOURCES: We reviewed the published animal
      and human literature on isocyanate skin-exposure methods, workplace skin
      exposure, skin absorption, and the role of skin exposure in isocyanate
      sensitization and asthma. DATA EXTRACTION: We selected relevant articles from
      computerized searches on Medline, U.S. Environmental Protection Agency,
      Occupational Safety and Health Administration, National Institute for
      Occupational Safety and Health, and Google databases using the keywords
      "isocyanate," "asthma," "skin," "sensitization," and other synonymous terms, and
      our own extensive collection of isocyanate publications. DATA SYNTHESIS:
      Isocyanate production and use continues to increase as the polyurethane industry
      expands. There is substantial opportunity for isocyanate skin exposure in many
      work settings, but such exposure is challenging to quantify and continues to be
      underappreciated. Isocyanate skin exposure can occur at work, even with the use
      of personal protective equipment, and may also occur with consumer use of certain
      isocyanate products. In animals, isocyanate skin exposure is an efficient route
      to induce sensitization, with subsequent inhalation challenge resulting in asthma
      like responses. Several lines of evidence support a similar role for human
      isocyanate skin exposure, namely, that such exposure occurs and can contribute to
      the development of isocyanate asthma in certain settings, presumably by inducing
      systemic sensitization. CONCLUSIONS: Integrated animal and human research is
      needed to better understand the role of skin exposure in human isocyanate asthma
      and to improve diagnosis and prevention. In spite of substantial research needs,
      sufficient evidence already exists to justify greater emphasis on the potential
      risks of isocyanate skin exposure and the importance of preventing such exposures
      at work and during consumer use of certain isocyanate products.

PMID- 17431480
TI  - Serum dioxin concentrations and quality of ovarian function in women of Seveso.
AB  - BACKGROUND: Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been
      associated with alterations in ovarian function and hormones in animals, it has
      not been studied in humans. On 10 July 1976, an explosion exposed residents of
      Seveso, Italy, to the highest levels of TCDD in a population. Twenty years later,
      we initiated the Seveso Women's Health Study to study reproductive health.
      OBJECTIVE: We related TCDD levels measured in sera collected near the time of
      explosion and ovarian function (ovarian cysts, ovarian follicles, ovulation rate,
      serum hormones) at follow-up. METHODS: We included 363 women who were 20-40 years
      of age and nonusers of oral contraceptives. We examined the relationship of 1976
      serum TCDD levels with ultrasound-detected ovarian follicles among 96 women in
      the menstrual follicular phase and serum hormone levels (estradiol, progesterone)
      among 129 women in the menstrual luteal phase at follow-up. Ovulation was defined
      by serum progesterone levels > 3 ng/mL. RESULTS: The median serum TCDD level was
      77.3 ppt, lipid-adjusted. Serum TCDD was not associated with number or size of
      ovarian follicles. Of women in the luteal phase, 87 (67%) ovulated. Serum
      log(10)TCDD was not associated with odds of ovulation [adjusted odds ratio =
      0.99; 95% confidence interval (CI), 0.5 to 1.9]. Among those who had ovulated,
      serum log(10)TCDD was not associated with serum progesterone [adjusted beta (adj
      beta ) = -0.70; 95% CI, -2.4 to 1.0] or estradiol (adj-beta = -1.81; 95% CI, 
      10.4 to 6.8). CONCLUSIONS: We found no clear evidence that 1976 TCDD exposure was
      associated with ovarian function 20 years later in women exposed to relatively
      high levels in Seveso, Italy.

PMID- 17431482
TI  - Impact of trivalent arsenicals on selenoprotein synthesis.
AB  - BACKGROUND: Exposure to arsenic has been associated with development of skin,
      lung, bladder, liver, and kidney cancer. Recent evidence suggests that an
      increase in oxidative stress in cells treated with arsenicals represents the
      molecular mechanism behind arsenic-induced carcinogenesis. Selenium, in the form
      of selenocysteine, is necessary for the activity of several enzymes with a role
      in defense against reactive oxygen species. A mutual sparing effect between
      arsenic and selenium has been shown in animal studies when both metalloids are
      present in high concentrations. OBJECTIVES: To determine whether changes in
      selenoprotein synthesis may be an underlying mechanism behind arsenic-induced
      carcinogenesis, we analyzed the new synthesis of selenoproteins within cells
      after exposure to inorganic or methylated arsenicals using a human keratinocyte
      cell model. RESULTS: Addition of arsenite to culture medium blocked new synthesis
      of selenoproteins when selenium was present in the form of selenite, and appeared
      to stimulate the use of serum-derived selenium. Monomethylarsonous acid
      (MMA(III)) treatment of cells, in contrast, did not block all new synthesis of
      selenoproteins but did result in an increase in cytosolic thioredoxin reductase
      (TrxR1) at both the mRNA and protein levels. MMA(III) also reduced the new
      synthesis of cellular glutatione peroxidase (cGpx) and other smaller
      selenoproteins. Dimethylarsinous acid (DMA(III)) stimulated selenoprotein
      synthesis by an as yet unknown mechanism. CONCLUSIONS: These results suggest that
      arsenite and MMA(III) are key metabolites that trigger higher levels of TrxR1,
      and both lead to a reduction in the expression of cGpx. Together these effects
      certainly could lead to carcinogenesis given the knowledge that many cancers have
      higher levels of TrxR, and reduced Gpx levels will reduce the cell's ability to
      defend against reactive oxygen species. Based on these results, the impact of the
      trivalent arsenicals arsenite and MMA(III) on selenoprotein synthesis may indeed
      represent a potential molecular mechanism for the higher rates of cancer observed
      in populations exposed to high levels of arsenic.

PMID- 17431481
TI  - Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesions.
AB  - OBJECTIVE: We investigated whether primary and secondary arsenic methylation
      ratios were associated with skin lesions and whether GSTT1, GSTP1, and GSTM1
      polymorphisms modify these relationships. METHODS: A case-control study of 600
      cases and 600 controls that were frequency matched on age and sex was conducted
      in Pabna, Bangladesh, in 2001-2002. Individual well water, urine, and blood
      samples were collected. Water arsenic concentration was determined using
      inductively coupled plasma mass spectrometry (ICP-MS). Urinary arsenic speciation
      was determined using high performance liquid chromatography hydride with
      generator atomic absorption spectrometry and ICP-MS. Genotyping was conducted
      using multiplex polymerase chain reaction and TaqMan. RESULTS: A 10-fold increase
      in primary methylation ratio [monomethylarsonic acid (MMA)/(arsenite + arsenate]
      was associated with a 1.50-fold increased risk of skin lesions (multivariate odds
      ratio = 1.50; 95% confidence interval, 1.00-2.26). We observed significant
      interaction on the multiplicative scale between GSTT1 wildtype and secondary
      methylation ratio [dimethylarsinic acid/MMA; likelihood ratio test (LRT), p =
      0.01]. No significant interactions were observed for GSTM1 or GSTP1 or for
      primary methylation ratios. CONCLUSION: Our findings suggest that increasing
      primary methylation ratios are associated with an increase in risk of arsenic
      related skin lesions. The interaction between GSTT1 wildtype and secondary
      methylation ratio modifies risk of skin lesions among arsenic-exposed
      individuals.

PMID- 17431483
TI  - Low-dose exposure and immunogenicity of transgenic maize expressing the
      Escherichia coli heat-labile toxin B subunit.
AB  - BACKGROUND: Transgenic maize, which produces the nontoxic B subunit of the
      Escherichia coli heat-labile toxin (LT-B) in seed, has proven to be an effective
      oral immunogen in mice. Currently, there is considerable concern over accidental
      consumption of transgenic maize expressing LT-B by humans and domestic animals.
      We have yet to define nonimmunogenic levels of transgenic LT-B when ingested.
      OBJECTIVES: Our goal in this study was to determine the highest dose of LT-B
      orally administered in mice that does not result in a measurable immune response.
      We defined an immune response as specific serum or mucosal IgG or IgA
      significantly greater than background after three feedings (0.0002-20 mug) or a
      priming response induced by the intermittent feeding. METHODS: We fed transgenic
      maize pellets on days 0, 7, 21, and 49 and collected serum and fecal samples
      weekly. Serum was analyzed for LT-B-specific IgG and IgA, and feces was analyzed
      for LT-B-specific IgA. RESULTS: We observed a dose-dependent anti-LT-B antibody
      response with high specific antibody concentrations in groups fed high doses
      (0.2, 2, 20 mug) of LT-B maize. Mice fed 0.02 mug LT-B demonstrated immune
      priming in 62.5% of the animals. Mice that were fed </= 0.002 mug LT-B showed no
      increase in specific antibody nor did they demonstrate immune priming, indicating
      that 0.002 mug LT-B was the highest nonimmunogenic dose tested. CONCLUSION: Our
      results demonstrate that LT-B derived from transgenic maize is immunogenic at
      nanogram levels when orally administered to mice.

PMID- 17431485
TI  - Biomonitoring of 2,4-dichlorophenoxyacetic acid exposure and dose in farm
      families.
AB  - OBJECTIVE: We estimated 2,4-dichlorophenoxyacetic acid (2,4-D) exposure and
      systemic dose in farm family members following an application of 2,4-D on their
      farm. METHODS: Farm families were recruited from licensed applicators in
      Minnesota and South Carolina. Eligible family members collected all urine during
      five 24-hr intervals, 1 day before through 3 days after an application of 2,4-D.
      Exposure profiles were characterized with 24-hr urine 2,4-D concentrations, which
      then were related to potential predictors of exposure. Systemic dose was
      estimated using the urine collections from the application day through the third
      day after application. RESULTS: Median urine 2,4-D concentrations at baseline and
      day after application were 2.1 and 73.1 microg/L for applicators, below the limit
      of detection, and 1.2 microg/L for spouses, and 1.5 and 2.9 microg/L for
      children. The younger children (4-11 years of age) had higher median post
      application concentrations than the older children (> or = 12 years of age) (6.5
      vs. 1.9 microg/L). The geometric mean systemic doses (micrograms per kilogram
      body weight) were 2.46 (applicators), 0.8 (spouses), 0.22 (all children), 0.32
      (children 4-11 years of age), and 0.12 (children > or = 12 years of age).
      Exposure to the spouses and children was primarily determined by direct contact
      with the application process and the number of acres treated. Multivariate models
      identified glove use, repairing equipment, and number of acres treated as
      predictors of exposure in the applicators. CONCLUSIONS: We observed considerable
      heterogeneity of 2,4-D exposure among farm family members, primarily attributable
      to level of contact with the application process. Awareness of this variability
      and the actual magnitude of exposures are important for developing exposure and
      risk characterizations in 2,4-D-exposed agricultural populations.

PMID- 17431484
TI  - Evaluation of the U.S. EPA/OSWER preliminary remediation goal for perchlorate in
      groundwater: focus on exposure to nursing infants.
AB  - BACKGROUND: Perchlorate is a common contaminant of drinking water and food. It
      competes with iodide for uptake into the thyroid, thus interfering with thyroid
      hormone production. The U.S. Environmental Protection Agency's Office of Solid
      Waste and Emergency Response (OSWER) set a groundwater preliminary remediation
      goal (PRG) of 24.5 microg/L to prevent exposure of pregnant women that would
      affect the fetus. This does not account for the greater exposure that is possible
      in nursing infants or for the relative source contribution (RSC), a factor
      normally used to lower the PRG due to nonwater exposures. OBJECTIVES: Our goal
      was to assess whether the OSWER PRG protects infants against exposures from
      breast-feeding, and to evaluate the perchlorate RSC. METHODS: We used Monte Carlo
      analysis to simulate nursing infant exposures associated with the OSWER PRG when
      combined with background perchlorate. RESULTS: The PRG can lead to a 7-fold
      increase in breast milk concentration, causing 90% of nursing infants to exceed
      the reference dose (RfD) (average exceedance, 2.8-fold). Drinking-water
      perchlorate must be < 6.9 microg/L to keep the median, and < 1.3 microg/L to keep
      the 90th-percentile nursing infant exposure below the RfD. This is 3.6- to 19
      fold below the PRG. Analysis of biomonitoring data suggests an RSC of 0.7 for
      pregnant women and of 0.2 for nursing infants. Recent data from the Centers for
      Disease Control and Prevention (CDC) suggest that the RfD itself needs to be
      reevaluated because of hormonal effects in the general population. CONCLUSIONS:
      The OSWER PRG for perchlorate can be improved by considering infant exposures, by
      incorporating an RSC, and by being responsive to any changes in the RfD resulting
      from the new CDC data.

PMID- 17431486
TI  - Cardiovascular effects of pulmonary exposure to single-wall carbon nanotubes.
AB  - BACKGROUND: Engineered nanosized materials, such as single-wall carbon nanotubes
      (SWCNT), are emerging as technologically important in different industries.
      OBJECTIVE: The unique physical characteristics and the pulmonary toxicity of
      SWCNTs raised concerns that respiratory exposure to these materials may be
      associated with cardiovascular adverse effects. METHODS: In these studies we
      evaluated aortic mitochondrial alterations by oxidative stress assays, including
      quantitative polymerase chain reaction of mitochondrial (mt) DNA and plaque
      formation by morphometric analysis in mice exposed to SWCNTs. RESULTS: A single
      intrapharyngeal instillation of SWCNTs induced activation of heme oxygenase-1 (HO
      1), a marker of oxidative insults, in lung, aorta, and heart tissue in HO-1
      reporter transgenic mice. Furthermore, we found that C57BL/6 mice, exposed to
      SWCNT (10 and 40 mug/mouse), developed aortic mtDNA damage at 7, 28, and 60 days
      after exposure. mtDNA damage was accompanied by changes in aortic mitochondrial
      glutathione and protein carbonyl levels. Because these modifications have been
      related to cardiovascular diseases, we evaluated whether repeated exposure to
      SWCNTs (20 mug/mouse once every other week for 8 weeks) stimulates the
      progression of atherosclerosis in ApoE(-/-) transgenic mice. Although SWCNT
      exposure did not modify the lipid profiles of these mice, it resulted in
      accelerated plaque formation in ApoE(-/-) mice fed an atherogenic diet. Plaque
      areas in the aortas, measured by the en face method, and in the brachiocephalic
      arteries, measured histopathologically, were significantly increased in the SWCNT
      treated mice. This response was accompanied by increased mtDNA damage but not
      inflammation. CONCLUSIONS: Taken together, the findings are of sufficient
      significance to warrant further studies to evaluate the systemic effects of SWCNT
      under workplace or environmental exposure paradigms.

PMID- 17431487
TI  - Within- and between-home variability in indoor-air insecticide levels during
      pregnancy among an inner-city cohort from New York City.
AB  - BACKGROUND: Residential insecticide use is widespread in the United States, but
      few data are available on the persistence and variability in levels in the indoor
      environment. OBJECTIVE: The study aim was to assess within- and between-home
      variability in indoor-air insecticides over the final 2 months of pregnancy among
      a cohort of African-American and Dominican women from New York City. METHODS:
      Women not employed outside the home were enrolled between February 2001 and May
      2004 (n = 102); 9 insecticides and an adjuvant were measured in 48-hr personal
      air samples and 2-week integrated indoor air samples collected sequentially for
      7.0 +/- 2.3 weeks (n = 337 air samples). RESULTS: Sixty-one percent of the women
      reported using pest control during the air samplings. Chlorpyrifos, diazinon, and
      propoxur were detected in 99-100% of personal and indoor samples (range, 0.4-641
      ng/m(3)). Piperonyl butoxide (a pyrethroid adjuvant) was detected in 45.5-68.5%
      (0.2-608 ng/m(3)). There was little within-home variability and no significant
      difference in air concentrations within homes over time (p > or = 0.2); between
      home variability accounted for 88% of the variance in the indoor air levels of
      propoxur, 92% in chlorpyrifos, 94% in diazinon, and 62% in piperonyl butoxide (p
      < 0.001). Indoor and maternal personal air insecticide levels were highly
      correlated (r = 0.7-0.9, p < 0.001). Diazinon and chlorpyrifos levels declined 5
      fold between 2001 and 2004 but were detected in all homes 1.5 and 2.5 years,
      respectively, after the U.S. Environmental Protection Agency ban on their
      residential use. CONCLUSION: Results showed that the insecticides were persistent
      in the home with little variability in air concentrations over the 2 months and
      contributed to chronic maternal inhalation exposures during pregnancy.

PMID- 17431488
TI  - Effects of monobutyl and di(n-butyl) phthalate in vitro on steroidogenesis and
      Leydig cell aggregation in fetal testis explants from the rat: comparison with
      effects in vivo in the fetal rat and neonatal marmoset and in vitro in the human.
AB  - BACKGROUND: Certain phthalates can impair Leydig cell distribution and
      steroidogenesis in the fetal rat in utero, but it is unknown whether similar
      effects might occur in the human. OBJECTIVES: Our aim in this study was to
      investigate the effects of di(n-butyl) phthalate (DBP), or its metabolite
      monobutyl phthalate (MBP), on testosterone production and Leydig cell aggregation
      (LCA) in fetal testis explants from the rat and human, and to compare the results
      with in vivo findings for DBP-exposed rats. We also wanted to determine if
      DBP/MBP affects testosterone production in vivo in the neonatal male marmoset.
      METHODS: Fetal testis explants obtained from the rat [gestation day (GD)19.5] and
      from the human (15-19 weeks of gestation) were cultured for 24-48 hr with or
      without human chorionic gonadotropin (hCG) or 22R-hydroxycholesterol (22R-OH),
      and with or without DBP/MBP. Pregnant rats and neonatal male marmosets were dosed
      with 500 mg/kg/day DBP or MBP. RESULTS: Exposure of rats in utero to DBP (500
      mg/kg/day) for 48 hr before GD21.5 induced major suppression of intratesticular
      testosterone levels and cytochrome P450 side chain cleavage enzyme (P450scc)
      expression; this short-term treatment induced LCA, but was less marked than
      longer term (GD13.5-20.5) DBP treatment. In vitro, MBP (10(-3) M) did not affect
      basal or 22R-OH-stimulated testosterone production by fetal rat testis explants
      but slightly attenuated hCG-stimulated steroidogenesis; MBP induced minor LCA in
      vitro. None of these parameters were affected in human fetal testis explants
      cultured with 10(-3) M MBP for up to 48 hr. Because the in vivo effects of
      DBP/MBP were not reproduced in vitro in the rat, the absence of MBP effects in
      vitro on fetal human testes is inconclusive. In newborn (Day 2-7) marmosets,
      administration of a single dose of 500 mg/kg MBP significantly (p = 0.019)
      suppressed blood testosterone levels 5 hr later. Similar treatment of newborn co
      twin male marmosets for 14 days resulted in increased Leydig cell volume per
      testis (p = 0.011), compared with co-twin controls; this is consistent with MBP
      induced inhibition of steroidogenesis followed by compensatory Leydig cell
      hyperplasia/hypertrophy. CONCLUSIONS: These findings suggest that MBP/DBP
      suppresses steroidogenesis by fetal-type Leydig cells in primates as in rodents,
      but this cannot be studied in vitro.

PMID- 17431489
TI  - Inhalation exposure study of titanium dioxide nanoparticles with a primary
      particle size of 2 to 5 nm.
AB  - BACKGROUND: Nanotechnology offers great promise in many industrial applications.
      However, little is known about the health effects of manufactured nanoparticles,
      the building blocks of nanomaterials. OBJECTIVES: Titanium dioxide (TiO(2))
      nanoparticles with a primary size of 2-5 nm have not been studied previously in
      inhalation exposure models and represent some of the smallest manufactured
      nanoparticles. The purpose of this study was to assess the toxicity of these
      nanoparticles using a murine model of lung inflammation and injury. MATERIALS AND
      METHODS: The properties of TiO(2) nanoparticles as well as the characteristics of
      aerosols of these particles were evaluated. Mice were exposed to TiO(2)
      nanoparticles in a whole-body exposure chamber acutely (4 hr) or subacutely (4
      hr/day for 10 days). Toxicity in exposed mice was assessed by enumeration of
      total and differential cells, determination of total protein, lactate
      dehydrogenase (LDH) activity and inflammatory cytokines in bronchoalveolar lavage
      (BAL) fluid. Lungs were also evaluated for histopathologic changes RESULTS: Mice
      exposed acutely to 0.77 or 7.22 mg/m(3) nanoparticles demonstrated minimal lung
      toxicity or inflammation. Mice exposed subacutely (8.88 mg/m(3)) and necropsied
      immediately and at week 1 or 2 postexposure had higher counts of total cells and
      alveolar macrophages in the BAL fluid compared with sentinels. However, mice
      recovered by week 3 postexposure. Other indicators were negative. CONCLUSIONS:
      Mice subacutely exposed to 2-5 nm TiO(2) nanoparticles showed a significant but
      moderate inflammatory response among animals at week 0, 1, or 2 after exposure
      that resolved by week 3 postexposure.

PMID- 17431490
TI  - Induction of inflammation in vascular endothelial cells by metal oxide
      nanoparticles: effect of particle composition.
AB  - BACKGROUND: The mechanisms governing the correlation between exposure to
      ultrafine particles and the increased incidence of cardiovascular disease remain
      unknown. Ultrafine particles appear to cross the pulmonary epithelial barrier
      into the bloodstream, raising the possibility of direct contact with the vascular
      endothelium. OBJECTIVES: Because endothelial inflammation is critical for the
      development of cardiovascular pathology, we hypothesized that direct exposure of
      human aortic endothelial cells (HAECs) to ultrafine particles induces an
      inflammatory response and that this response depends on particle composition.
      METHODS: To test the hypothesis, we incubated HAECs for 1-8 hr with different
      concentrations (0.001-50 mug/mL) of iron oxide (Fe(2)O(3)), yttrium oxide
      (Y(2)O(3)), and zinc oxide (ZnO) nanoparticles and subsequently measured mRNA and
      protein levels of the three inflammatory markers intra-cellular cell adhesion
      molecule-1, interleukin-8, and monocyte chemotactic protein-1. We also determined
      nanoparticle interactions with HAECs using inductively coupled plasma mass
      spectrometry and transmission electron microscopy. RESULTS: Our data indicate
      that nanoparticle delivery to the HAEC surface and uptake within the cells
      correlate directly with particle concentration in the cell culture medium. All
      three types of nanoparticles are internalized into HAECs and are often found
      within intracellular vesicles. Fe(2)O(3) nanoparticles fail to provoke an
      inflammatory response in HAECs at any of the concentrations tested; however,
      Y(2)O(3) and ZnO nanoparticles elicit a pronounced inflammatory response above a
      threshold concentration of 10 mug/mL. At the highest concentration, ZnO
      nanoparticles are cytotoxic and lead to considerable cell death. CONCLUSIONS:
      These results demonstrate that inflammation in HAECs following acute exposure to
      metal oxide nanoparticles depends on particle composition.

PMID- 17431491
TI  - Estimating risk from ambient concentrations of acrolein across the United States.
AB  - BACKGROUND: Estimated ambient concentrations of acrolein, a hazardous air
      pollutant, are greater than the U.S. Environmental Protection Agency (EPA)
      reference concentration throughout the United States, making it a concern for
      human health. However, there is no method for assessing the extent of risk under
      the U.S. EPA noncancer risk assessment framework. OBJECTIVES: We estimated excess
      risks from ambient concentrations of acrolein based on dose-response modeling of
      a study in rats with a relationship between acrolein and residual volume/total
      lung capacity ratio (RV/TLC) and specific compliance (sC(L)), markers for altered
      lung function. METHODS: Based on existing literature, we defined values above the
      90th percentile for controls as "adverse." We estimated the increase over
      baseline response that would occur in the human population from estimated ambient
      concentrations of acrolein, taken from the U.S. EPA's National-Scale Air Toxics
      Assessment for 1999, after standard animal-to-human conversions and extrapolating
      to doses below the experimental data. RESULTS: The estimated median additional
      number of adverse sC(L) outcomes across the United States was approximately 2.5
      cases per 1,000 people. The estimated range of additional outcomes from the 5th
      to the 95th percentile of acrolein concentration levels across census tracts was
      0.28-14 cases per 1,000. For RV/TLC, the median additional outcome was 0.002 per
      1,000, and the additional outcome at the 95th percentile was 0.13 per 1,000.
      CONCLUSIONS: Although there are uncertainties in estimating human risks from
      animal data, this analysis demonstrates a method for estimating health risks for
      noncancer effects and suggests that acrolein could be associated with decreased
      respiratory function in the United States.

PMID- 17431492
TI  - Workgroup report: base stations and wireless networks-radiofrequency (RF)
      exposures and health consequences.
AB  - Radiofrequency (RF) waves have long been used for different types of information
      exchange via the air waves--wireless Morse code, radio, television, and wireless
      telephone (i.e., construction and operation of telephones or telephone systems).
      Increasingly larger numbers of people rely on mobile telephone technology, and
      health concerns about the associated RF exposure have been raised, particularly
      because the mobile phone handset operates in close proximity to the human body,
      and also because large numbers of base station antennas are required to provide
      widespread availability of service to large populations. The World Health
      Organization convened an expert workshop to discuss the current state of cellular
      telephone health issues, and this article brings together several of the key
      points that were addressed. The possibility of RF health effects has been
      investigated in epidemiology studies of cellular telephone users and workers in
      RF occupations, in experiments with animals exposed to cell-phone RF, and via
      biophysical consideration of cell-phone RF electric-field intensity and the
      effect of RF modulation schemes. As summarized here, these separate avenues of
      scientific investigation provide little support for adverse health effects
      arising from RF exposure at levels below current international standards.
      Moreover, radio and television broadcast waves have exposed populations to RF for
      > 50 years with little evidence of deleterious health consequences. Despite
      unavoidable uncertainty, current scientific data are consistent with the
      conclusion that public exposures to permissible RF levels from mobile telephone
      and base stations are not likely to adversely affect human health.

PMID- 17431493
TI  - Quality of life and capsaicin sensitivity in patients with airway symptoms
      induced by chemicals and scents: a longitudinal study.
AB  - OBJECTIVE: It is common in asthma and allergy clinics to see patients presenting
      with upper and lower airway symptoms that are induced by chemicals and scents and
      not explained by allergic or asthmatic reactions. Previous studies have shown
      that these patients often have increased cough sensitivity to inhaled capsaicin;
      such sensitivity is known to reflect the airway sensory reactivity. The aim of
      this study was to evaluate the duration of symptoms induced by chemicals and
      scents and to measure health-related quality of life (HRQL) in patients with
      chemically induced airway symptoms. We also wished to determine and compare
      repeatability of the cough response to capsaicin inhalation, and to evaluate the
      patients' airway sensory reactivity in a long-term perspective. PARTICIPANTS:
      Seventeen patients with a history of at least 12 months of airway symptoms
      induced by chemicals and scents were followed over 5 years with repeated
      questionnaires, measurements of HRQL, and capsaicin inhalation tests. RESULTS:
      The symptoms persisted and did not change significantly over time, and the
      patients had a reduced HRQL that did not change during the 5-year period. The
      capsaicin sensitivity was increased at the start of the study, the cough
      sensitivity was long-lasting, and the repeatability of the capsaicin inhalation
      test was considered to be good in a long-term perspective. CONCLUSIONS: Upper and
      lower airway symptoms induced by chemicals and scents represent an entity of
      chronic diseases, different from asthma or chronic obstructive pulmonary disease,
      with persistent symptoms, a reduced HRQL, and unchanged sensory hyperreactivity.

PMID- 17431494
TI  - Metals in particulate pollutants affect peak expiratory flow of schoolchildren.
AB  - BACKGROUND: The contribution of the metal components of particulate pollutants to
      acute respiratory effects has not been adequately evaluated. Moreover, little is
      known about the effects of genetic polymorphisms of xenobiotic metabolism on
      pulmonary function. OBJECTIVES: This study was conducted to assess lung function
      decrement associated with metal components in particulate pollutants and genetic
      polymorphisms of glutathione S-transferase M1 and T1. METHODS: We studied 43
      schoolchildren who were in the 3rd to 6th grades. Each student measured peak
      expiratory flow rate three times a day for 42 days. Particulate air
      concentrations were monitored every day, and the concentrations of iron,
      manganese, lead, zinc, and aluminum in the particles were measured. Glutathione S
      transferase M1 and T1 genetic polymorphisms were determined using DNA extracted
      from participant buccal washings. We used a mixed linear regression model to
      estimate the association between peak expiratory flow rate and particulate air
      pollutants. RESULTS: We found significant reduction in the peak expiratory flow
      rate after the children's exposure to particulate pollutants. The effect was
      shown most significantly 1 day after exposure to the ambient particles. Manganese
      and lead in the particles also reduced the peak expiratory flow rate. Genetic
      polymorphisms of glutathione S-transferase M1 and T1 did not significantly affect
      peak expiratory flow rate. CONCLUSIONS: This study demonstrated that particulate
      pollutants and metals such as manganese and lead in the particles are associated
      with a decrement of peak expiratory flow rate. These effects were robust even
      with consideration of genetic polymorphisms of glutathione S-transferase.

PMID- 17431495
TI  - In utero p,p'-DDE exposure and infant neurodevelopment: a perinatal cohort in
      Mexico.
AB  - BACKGROUND: Evidence suggests that p,p'-dichlorodiphenyldichloroethene (DDE)
      affects neurodevelopment in infants, although a critical exposure window has not
      yet been identified. OBJECTIVES: Our goal was to assess the prenatal DDE exposure
      window and its effect on the psychomotor development index (PDI) and mental
      development index (MDI) during the first year of life. METHODS: We recruited 244
      children whose pregnancies and deliveries were uncomplicated, and whose mothers
      were monitored throughout the pregnancy. Participating mothers were not
      occupationally exposed to DDT (dichlorodiphenyltrichloroethane) but were
      residents of a zone in Mexico with endemic malaria. We measured serum levels of
      DDE before pregnancy and during each trimester of the pregnancy. We evaluated PDI
      and MDI of the Bayley Scales for Infant Development (BSID-II), at 1, 3, 6, and 12
      months of age. We adjusted for quality of the home environment and maternal
      intellectual coefficient (IQ). We used generalized mixed-effects models for
      statistical analysis. RESULTS: Third-trimester DDE level (7.8 +/- 2.8 ppb) was
      significantly higher than the level at baseline, first, and second trimesters,
      but the differences never exceeded 20%. Only DDE levels during the first
      trimester of pregnancy were associated with a significant reduction in PDI (every
      doubled increase of DDE level reduced the PDI 0.5 points). DDE was not associated
      with MDI. CONCLUSIONS: A critical window of exposure to DDE in utero may be the
      first trimester of the pregnancy, and psychomotor development is a target of this
      compound. Residues of DDT metabolites may present a risk of developmental delay
      for years after termination of DDT use.

PMID- 17431496
TI  - Dental amalgam restorations and children's neuropsychological function: the New
      England Children's Amalgam Trial.
AB  - BACKGROUND: A concern persists that children's exposure to mercury vapor from
      dental amalgams produces neurotoxicity. OBJECTIVE: Our goal was to compare the
      neuropsychological function of children, without prior exposure to dental
      amalgam, whose caries were repaired using either dental amalgam or mercury-free
      composite materials. METHODS: We conducted a randomized controlled trial
      involving 534 6- to 10-year-old urban and rural children who were assessed yearly
      for 5 years using a battery of tests of intelligence, achievement, language,
      memory, learning, visual-spatial skills, verbal fluency, fine motor function,
      problem solving, attention, and executive function. RESULTS: Although the mean
      urinary mercury concentration was greater among children in the amalgam group
      than the composite group (0.9 vs. 0.6 microg/g creatinine), few significant
      differences were found between the test scores of children in the two groups. The
      differences found were inconsistent in direction. Analyses using two cumulative
      exposure indices--surface years of amalgam and urinary mercury concentration-
      produced similar results. CONCLUSIONS: Exposure to elemental mercury in amalgam
      at the levels experienced by the children who participated in the trial did not
      result in significant effects on neuropsychological function within the 5-year
      follow-up period.

PMID- 17431497
TI  - Exposure to hexachlorobenzene during pregnancy and children's social behavior at
      4 years of age.
AB  - BACKGROUND: Hexachlorobenzene (HCB) is an organochlorine chemical that has been
      used in agriculture and industrial processes. Behavioral impairment after HCB
      exposure has been described in animal models, but little information is available
      in humans. OBJECTIVES: Our goal was to study the association of prenatal exposure
      to HCB with the social behavior of preschool children. METHODS: Two birth cohorts
      in Ribera d'Ebre and Menorca (Spain) were set up between 1997 and 1999 (n = 475).
      The California Preschool Social Competence Scale and the Attention-Deficit
      Hyperactivity Disorder (ADHD) were scored by each 4-year-old child's teacher.
      Organochlorine compounds were measured in cord serum. Children's diet and
      parental sociodemographic information were obtained through questionnaire.
      RESULTS: Children with concentrations of HCB > 1.5 ng/mL at birth had a
      statistically significant increased risk of having poor Social Competence
      [relative risk (RR) = 4.04; 95% confidence interval (CI), 1.76-9.58] and ADHD (RR
      = 2.71; 95% CI, 1.05-6.96) scores. No association was found between HCB and the
      cognitive and psychomotor performance of these children. CONCLUSIONS: Prenatal
      exposure to current concentrations of HCB in Spain is associated with a decrease
      in the behavioral competence at preschool ages. These results should be
      considered when evaluating the potential neurotoxicologic effects of HCB.

PMID- 17431498
TI  - Adult lead exposure: time for change.
AB  - We have assembled this mini-monograph on adult lead exposure to provide guidance
      to clinicians and public health professionals, to summarize recent thinking on
      lead biomarkers and their relevance to epidemiologic research, and to review two
      key lead-related outcomes, namely, cardiovascular and cognitive. The lead
      standards of the U.S. Occupational Safety and Health Administration are woefully
      out of date given the growing evidence of the health effects of lead at levels of
      exposure previously thought to be safe, particularly newly recognized persistent
      or progressive effects of cumulative dose. The growing body of scientific
      evidence suggests that occupational standards should limit recent dose to prevent
      the acute effects of lead and separately limit cumulative dose to prevent the
      chronic effects of lead. We hope this mini-monograph will motivate renewed
      discussion of ways to protect lead-exposed adults in the United States and around
      the world.

PMID- 17431499
TI  - The epidemiology of lead toxicity in adults: measuring dose and consideration of
      other methodologic issues.
AB  - We review several issues of broad relevance to the interpretation of
      epidemiologic evidence concerning the toxicity of lead in adults, particularly
      regarding cognitive function and the cardiovascular system, which are the
      subjects of two systematic reviews that are also part of this mini-monograph.
      Chief among the recent developments in methodologic advances has been the
      refinement of concepts and methods for measuring individual lead dose in terms of
      appreciating distinctions between recent versus cumulative doses and the use of
      biological markers to measure these parameters in epidemiologic studies of
      chronic disease. Attention is focused particularly on bone lead levels measured
      by K-shell X-ray fluorescence as a relatively new biological marker of cumulative
      dose that has been used in many recent epidemiologic studies to generate insights
      into lead's impact on cognition and risk of hypertension, as well as the
      alternative method of estimating cumulative dose using available repeated
      measures of blood lead to calculate an individual's cumulative blood lead index.
      We review the relevance and interpretation of these lead biomarkers in the
      context of the toxico-kinetics of lead. In addition, we also discuss methodologic
      challenges that arise in studies of occupationally and environmentally exposed
      subjects and those concerning race/ethnicity and socioeconomic status and other
      important covariates.

PMID- 17431500
TI  - Recommendations for medical management of adult lead exposure.
AB  - Research conducted in recent years has increased public health concern about the
      toxicity of lead at low dose and has supported a reappraisal of the levels of
      lead exposure that may be safely tolerated in the workplace. In this article,
      which appears as part of a mini-monograph on adult lead exposure, we summarize a
      body of published literature that establishes the potential for hypertension,
      effects on renal function, cognitive dysfunction, and adverse female reproductive
      outcome in adults with whole-blood lead concentrations < 40 microg/dL. Based on
      this literature, and our collective experience in evaluating lead-exposed adults,
      we recommend that individuals be removed from occupational lead exposure if a
      single blood lead concentration exceeds 30 microg/dL or if two successive blood
      lead concentrations measured over a 4-week interval are > or = 20 microg/dL.
      Removal of individuals from lead exposure should be considered to avoid long-term
      risk to health if exposure control measures over an extended period do not
      decrease blood lead concentrations to < 10 microg/dL or if selected medical
      conditions exist that would increase the risk of continued exposure. Recommended
      medical surveillance for all lead-exposed workers should include quarterly blood
      lead measurements for individuals with blood lead concentrations between 10 and
      19 microg/dL, and semiannual blood lead measurements when sustained blood lead
      concentrations are < 10 microg/dL. It is advisable for pregnant women to avoid
      occupational or avocational lead exposure that would result in blood lead
      concentrations > 5 microg/dL. Chelation may have an adjunctive role in the
      medical management of highly exposed adults with symptomatic lead intoxication
      but is not recommended for asymptomatic individuals with low blood lead
      concentrations.

PMID- 17431501
TI  - Lead exposure and cardiovascular disease--a systematic review.
AB  - OBJECTIVE: This systematic review evaluates the evidence on the association
      between lead exposure and cardiovascular end points in human populations.
      METHODS: We reviewed all observational studies from database searches and
      citations regarding lead and cardiovascular end points. RESULTS: A positive
      association of lead exposure with blood pressure has been identified in numerous
      studies in different settings, including prospective studies and in relatively
      homogeneous socioeconomic status groups. Several studies have identified a dose
      response relationship. Although the magnitude of this association is modest, it
      may be underestimated by measurement error. The hypertensive effects of lead have
      been confirmed in experimental models. Beyond hypertension, studies in general
      populations have identified a positive association of lead exposure with clinical
      cardiovascular outcomes (cardiovascular, coronary heart disease, and stroke
      mortality; and peripheral arterial disease), but the number of studies is small.
      In some studies these associations were observed at blood lead levels < 5
      microg/dL. CONCLUSIONS: We conclude that the evidence is sufficient to infer a
      causal relationship of lead exposure with hypertension. We conclude that the
      evidence is suggestive but not sufficient to infer a causal relationship of lead
      exposure with clinical cardiovascular outcomes. There is also suggestive but
      insufficient evidence to infer a causal relationship of lead exposure with heart
      rate variability. PUBLIC HEALTH IMPLICATIONS: These findings have immediate
      public health implications. Current occupational safety standards for blood lead
      must be lowered and a criterion for screening elevated lead exposure needs to be
      established in adults. Risk assessment and economic analyses of lead exposure
      impact must include the cardiovascular effects of lead. Finally, regulatory and
      public health interventions must be developed and implemented to further prevent
      and reduce lead exposure.

PMID- 17431502
TI  - Cumulative lead dose and cognitive function in adults: a review of studies that
      measured both blood lead and bone lead.
AB  - OBJECTIVE: We review empirical evidence for the relations of recent and
      cumulative lead dose with cognitive function in adults. DATA SOURCES: A
      systematic search of electronic databases resulted in 21 environmental and
      occupational studies from 1996 to 2006 that examined and compared associations of
      recent (in blood) and cumulative (in bone) lead doses with neurobehavioral
      outcomes. DATA EXTRACTION: Data were abstracted after consideration of exclusion
      criteria and quality assessment, and then compiled into summary tables.
      CONCLUSIONS: At exposure levels encountered after environmental exposure,
      associations with bio-markers of cumulative dose (mainly lead in tibia) were
      stronger and more consistent than associations with blood lead levels. Similarly,
      in studies of former workers with past occupational lead exposure, associations
      were also stronger and more consistent with cumulative dose than with recent dose
      (in blood). In contrast, studies of currently exposed workers generally found
      associations that were more apparent with blood lead levels; we speculate that
      the acute effects of high, recent dose may mask the chronic effects of cumulative
      dose. There is moderate evidence for an association between psychiatric symptoms
      and lead dose but only at high levels of current occupational lead exposure or
      with cumulative dose in environmentally exposed adults.

PMID- 17431503
TI  - Fanconi anemia pathway-deficient tumor cells are hypersensitive to inhibition of
      ataxia telangiectasia mutated.
AB  - The Fanconi anemia (FA) pathway maintains genomic stability in replicating cells.
      Some sporadic breast, ovarian, pancreatic, and hematological tumors are deficient
      in FA pathway function, resulting in sensitivity to DNA-damaging agents. FA
      pathway dysfunction in these tumors may result in hyperdependence on alternative
      DNA repair pathways that could be targeted as a treatment strategy. We used a
      high-throughput siRNA screening approach that identified ataxia telangiectasia
      mutated (ATM) as a critical kinase for FA pathway-deficient human fibroblasts.
      Human fibroblasts and murine embryonic fibroblasts deficient for the FA pathway
      were observed to have constitutive ATM activation and Fancg(-/-)Atm(-/-) mice
      were found to be nonviable. Abrogation of ATM function in FA pathway-deficient
      cells resulted in DNA breakage, cell cycle arrest, and apoptotic cell death.
      Moreover, Fanconi anemia complementation group G- (FANCG-) and FANCC-deficient
      pancreatic tumor lines were more sensitive to the ATM inhibitor KU-55933 than
      isogenic corrected lines. These data suggest that ATM and FA genes function in
      parallel and compensatory roles to maintain genomic integrity and cell viability.
      Pharmaceutical inhibition of ATM may have a role in the treatment of FA pathway
      deficient human cancers.

PMID- 17431504
TI  - CaMKII regulates retinoic acid receptor transcriptional activity and the
      differentiation of myeloid leukemia cells.
AB  - Retinoic acid receptors (RARs) are members of the nuclear hormone receptor family
      and regulate the proliferation and differentiation of multiple different cell
      types, including promyelocytic leukemia cells. Here we describe a
      biochemical/functional interaction between the Ca(2+)/calmodulin-dependent
      protein kinases (CaMKs) and RARs that modulates the differentiation of myeloid
      leukemia cells. We observe that CaMKIIgamma is the CaMK that is predominantly
      expressed in myeloid cells. CaMKII inhibits RAR transcriptional activity, and
      this enzyme directly interacts with RAR through a CaMKII LxxLL binding motif.
      CaMKIIgamma phosphorylates RARalpha both in vitro and in vivo, and this
      phosphorylation inhibits RARalpha activity by enhancing its interaction with
      transcriptional corepressors. In myeloid cell lines, CaMKIIgamma localizes to RAR
      target sites within myeloid gene promoters but dissociates from the promoter upon
      retinoic acid-induced myeloid cell differentiation. KN62, a pharmacological
      inhibitor of the CaMKs, enhances the terminal differentiation of myeloid leukemia
      cell lines, and this is associated with a reduction in activated
      (autophosphorylated) CaMKII in the terminally differentiating cells. These
      observations reveal a significant cross-talk between Ca(2+) and retinoic acid
      signaling pathways that regulates the differentiation of myeloid leukemia cells,
      and they suggest that CaMKIIgamma may provide a new therapeutic target for the
      treatment of certain human myeloid leukemias.

PMID- 17431505
TI  - Aberrant activation of AMP-activated protein kinase remodels metabolic network in
      favor of cardiac glycogen storage.
AB  - AMP-activated protein kinase (AMPK) responds to impaired cellular energy status
      by stimulating substrate metabolism for ATP generation. Mutation of the gamma2
      regulatory subunit of AMPK in humans renders the kinase insensitive to energy
      status and causes glycogen storage cardiomyopathy via unknown mechanisms. Using
      transgenic mice expressing one of the mutant gamma2 subunits (N488I) in the
      heart, we found that aberrant high activity of AMPK in the absence of energy
      deficit caused extensive remodeling of the substrate metabolism pathways to
      accommodate increases in both glucose uptake and fatty acid oxidation in the
      hearts of gamma2 mutant mice via distinct, yet synergistic mechanisms resulting
      in selective fuel storage as glycogen. Increased glucose entry in the gamma2
      mutant mouse hearts was directed through the remodeled metabolic network toward
      glycogen synthesis and, at a substantially higher glycogen level, recycled
      through the glycogen pool to enter glycolysis. Thus, the metabolic consequences
      of chronic activation of AMPK in the absence of energy deficiency is distinct
      from those previously reported during stress conditions. These findings are of
      particular importance in considering AMPK as a target for the treatment of
      metabolic diseases.

PMID- 17431506
TI  - Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak
      function of presenilin 1.
AB  - Mutations in presenilins are responsible for approximately 40% of all early-onset
      familial Alzheimer disease (FAD) cases in which a genetic cause has been
      identified. In addition, a number of mutations in presenilin-1 (PS1) have been
      suggested to be associated with the occurrence of frontal temporal dementia
      (FTD). Presenilins are highly conserved transmembrane proteins that support
      cleavage of the amyloid precursor protein by gamma-secretase. Recently, we
      discovered that presenilins also function as passive ER Ca(2+) leak channels.
      Here we used planar lipid bilayer reconstitution assays and Ca(2+) imaging
      experiments with presenilin-null mouse embryonic fibroblasts to analyze ER Ca(2+)
      leak function of 6 FAD-linked PS1 mutants and 3 known FTD-associated PS1 mutants.
      We discovered that L166P, A246E, E273A, G384A, and P436Q FAD mutations in PS1
      abolished ER Ca(2+) leak function of PS1. In contrast, A79V FAD mutation or FTD
      associated mutations (L113P, G183V, and Rins352) did not appear to affect ER
      Ca(2+) leak function of PS1 in our experiments. We validated our findings in
      Ca(2+) imaging experiments with primary fibroblasts obtained from an FAD patient
      possessing mutant PS1-A246E. Our results indicate that many FAD mutations in
      presenilins are loss-of-function mutations affecting ER Ca(2+) leak activity. In
      contrast, none of the FTD-associated mutations affected ER Ca(2+) leak function
      of PS1, indicating that the observed effects are disease specific. Our
      observations are consistent with the potential role of disturbed Ca(2+)
      homeostasis in Alzheimer disease pathogenesis.

PMID- 17431507
TI  - Early cardiac hypertrophy in mice with impaired calmodulin regulation of cardiac
      muscle Ca release channel.
AB  - Studies with isolated membrane fractions have shown that calmodulin (CaM)
      inhibits the activity of cardiac muscle cell Ca(2+) release channel ryanodine
      receptor 2 (RyR2). To determine the physiological importance of CaM regulation of
      RyR2, we generated a mouse with 3 amino acid substitutions (RyR2
      W3587A/L3591D/F3603A) in exon 75 of the Ryr2 gene, which encodes the CaM-binding
      site of RyR2. Homozygous mutant mice showed an increased ratio of heart weight to
      body weight, greatly reduced fractional shortening of the left ventricle, and
      lethality at 9-16 days of age. Biochemical analysis of hearts of 7- and 10-day
      old homozygous mutant mice indicated an impaired CaM inhibition of RyR2 at
      micromolar Ca(2+) concentrations, reduction in RyR2 protein levels and
      sarcoplasmic reticulum Ca(2+) sequestration, and upregulation of genes and/or
      proteins associated with class II histone deacetylase/myocyte enhancer factor-2
      and calcineurin signaling pathways. Sustained Ca(2+) transients, often displaying
      repeated periods of incomplete Ca(2+) removal, were observed in homozygous
      cardiomyocytes. Taken together, the data indicate that impaired CaM inhibition of
      RyR2, associated with defective sarcoplasmic reticulum Ca(2+) release and altered
      gene expression, leads to cardiac hypertrophy and early death.

PMID- 17431508
TI  - Endoscopic treatment for gastroesophageal reflux disease: should you learn the
      techniques?

PMID- 17431509
TI  - Photodynamic therapy for Barrett's esophagus with high-grade dysplasia: a cost
      effectiveness analysis.
AB  - OBJECTIVES: To assess the cost-effectiveness of photodynamic therapy (PDT) and
      esophagectomy (ESO) relative to surveillance (SURV) for patients with Barrett's
      esophagus (BE) and high-grade dysplasia (HGD). METHODS: A Markov decision tree
      was constructed to estimate costs and health outcomes of PDT, ESO and SURV in a
      hypothetical cohort of male patients, 50 years of age, with BE and HGD. Outcomes
      included unadjusted life-years (LYs) and quality-adjusted LYs (QALYs). Direct
      medical costs (2003 CDN$) were measured from the perspective of a provincial
      ministry of health. The time horizon for the model was five years (cycle length
      three months), and costs and outcomes were discounted at 3%. Model parameters
      were assigned unique distributions, and a probabilistic analysis with 10,000
      Monte Carlo simulations was performed. RESULTS: SURV was the least costly
      strategy, followed by PDT and ESO, but SURV was also the least effective. In
      terms of LYs, the incremental cost-effectiveness ratios were 814 dollars/LY for
      PDT versus SURV and 3,397 dollars/LY for ESO versus PDT. PDT dominated ESO for
      QALYs in the base-case. The incremental cost-effectiveness ratio of PDT versus
      SURV was 879 dollars/QALY. In probabilistic analysis, PDT was most likely to be
      cost-effective at willingness-to-pay (WTP) values between 100 dollars/LY and
      3,500 dollars/LY, and ESO was most likely to be cost-effective for WTP values
      over 3500 dollars/LY. For quality-adjusted survival, PDT was most likely to be
      cost-effective for all WTP thresholds above 1,000 dollars/QALY. The likelihood
      that PDT was the most cost-effective strategy reached 0.99 at a WTP ceiling of
      25,000 dollars/QALY. CONCLUSIONS: In male patients with BE and HGD, PDT and ESO
      are cost-effective alternatives to SURV.

PMID- 17431510
TI  - Aspiration in the context of upper gastrointestinal endoscopy.
AB  - BACKGROUND: Pulmonary aspiration is a life-threatening complication of upper
      gastrointestinal endoscopy, the incidence of which has not been determined.
      Endoscopy-related aspiration has not been studied in procedures in which patients
      swallow a radiolabelled potential aspirate immediately before endoscopy and
      undergo nuclear scanning postprocedure. METHODS: A pilot study was conducted in
      which 200 MBq of nonabsorbable technetium-99m phytate in 10 mL of water was
      administered orally to 50 patients who were about to undergo endoscopy. Gamma
      camera images were obtained to ensure that there had been no aspiration before
      endoscopy. After endoscopy, a repeat scan was performed. Fluid aspirated through
      the endoscope was also collected and analyzed for radioactivity using a hand-held
      radiation monitor. RESULTS: No evidence of pulmonary aspiration was found in any
      of the patients studied. The mean estimated percentage of the initially
      administered radioactivity aspirated through the endoscope was 2.66% (range 0% to
      10.3%). CONCLUSION: The present pilot study confirms earlier observations that
      clinically significant aspiration in the context of upper gastrointestinal
      endoscopy is uncommon. The incidence of aspiration may, however, be different in
      acutely bleeding patients undergoing endoscopy. For logistic reasons, this group
      could not be studied.

PMID- 17431511
TI  - Changes in renal function following administration of oral sodium phosphate or
      polyethylene glycol for colon cleansing before colonoscopy.
AB  - Changes in renal function were compared in patients receiving oral sodium
      phosphate (NaP) for colon cleansing and those receiving large-volume polyethylene
      glycol (PEG) solution to determine whether oral NaP resulted in frequent renal
      damage that had gone clinically undetected. From 1995 to 2004, a cohort of
      consecutive patients who had serum creatinine (Cr) drawn immediately before
      colonoscopy and again after subsequent procedures three months to nine years
      later (almost 80% of patients between the first and fifth year) were identified.
      Chronic renal failure (CRF) was defined as an abnormal Cr at repeat measurement
      or an abnormal Cr clearance as estimated by the Cockroft-Gault equation at the
      time of repeat Cr measurement. Medications and medical comorbid conditions were
      recorded. Seven hundred sixty-seven patients (51% female and 49% male; 81% oral
      NaP and 19% PEG) with normal baseline Cr levels were identified through the
      endoscopy unit database at the Hotel Dieu Hospital, Queen's University (Kingston,
      Ontario). Of these, 55 (7%) developed CRF. Forty-two (6.8%) patients receiving
      oral NaP developed renal failure compared with 13 patients (8.7%) receiving PEG
      (Fisher's exact test; P=0.382), but the magnitude of CRF was small in each group
      (Cr level lower than 160 mumol/L). Using logistic regression analysis with the
      choice of preparation, medications and medical comorbid conditions as independent
      variables, only age and blood pressure were predictive of the development of
      renal failure (P=0.014 and P=0.001, respectively). Baseline Cr clearance was
      similar in both the NaP and PEG groups and the absolute difference after
      colonoscopy did not differ. The present study concluded that the ingestion of
      oral NaP for colon cleansing before colonoscopy did not result in frequent renal
      damage that went clinically undetected.

PMID- 17431512
TI  - Colonic polyps in children and adolescents.
AB  - Colonic polyps most commonly present with rectal bleeding in children. The
      isolated juvenile polyp is the most frequent kind of polyp identified in
      children. 'Juvenile' refers to the histological type of polyp and not the age of
      onset of the polyp. Adolescents and adults with multiple juvenile polyps are at a
      significant risk of intestinal cancer. The challenge for adult and pediatric
      gastroenterologists is determining the precise risk of colorectal cancer in
      patients with juvenile polyposis syndrome. Attenuated familial adenamatous
      polyposis (AFAP) can occur either by a mutation at the extreme ends of the
      adenomatous polyposis coli gene or by biallelic mutations in the mutY homologue
      (MYH) gene. The identification of MYH-associated polyposis as an autosomal
      recessive condition has important implications for screening and management
      strategies. Adult and pediatric gastroenterologists need to be aware of the
      underlying inheritance patterns of polyposis syndromes so that patients and their
      families can be adequately evaluated and managed. Colonic polyps, including
      isolated juvenile polyps, juvenile polyposis syndrome, FAP, AFAP and MYH
      associated polyposis, are discussed in the present review.

PMID- 17431513
TI  - Oral manifestations of gastrointestinal diseases.
AB  - The present paper offers a detailed review of the oral manifestations of various
      gastrointestinal diseases or conditions, with suggestions on how they may be
      relevant to the practice of gastroenterology. The review includes Crohn's
      disease, ulcerative colitis, Gardner syndrome, Peutz-Jeghers syndrome,
      malabsorption conditions related to hematopoesis, gastrointestinal malignancy
      metastatic to the jaws, jaundice and gastric reflux diseases.

PMID- 17431514
TI  - Acute esophageal necrosis and low-flow state.
AB  - Acute esophageal necrosis (AEN), also called black esophagus, is quite
      exceptional. Endoscopic findings show circumferential black discolouration of the
      esophagus with or without exudates. The etiology of AEN is presently unknown and
      is assumed to be multifactorial. Distal esophageal involvement with proximal
      extension ending sharply at the gastroesophageal junction is the most common
      presentation. The present case report describes the clinical and endoscopic
      evolution of black esophagus observed in a patient with significant peripheral
      vascular disease, who was presented to the intensive care unit at the Hopital
      Saint-Francois d'Assise (Quebec City, Quebec). Through an extensive review of the
      literature, common underlying clinical conditions of patients diagnosed with AEN
      have been identified.

PMID- 17431516
TI  - Fluorescence correlation spectroscopy using quantum dots: advances, challenges
      and opportunities.
AB  - Semiconductor nanocrystals (quantum dots) have been increasingly employed in
      measuring the dynamic behavior of biomacromolecules using fluorescence
      correlation spectroscopy. This poses a challenge, because quantum dots display
      their own dynamic behavior in the form of intermittent photoluminescence, also
      known as blinking. In this review, the manifestation of blinking in correlation
      spectroscopy will be explored, preceded by an examination of quantum dot blinking
      in general.

PMID- 17431515
TI  - Endoscopic management of a relapsing hepatic hydatid cyst with intrabiliary
      rupture: a case report and review of the literature.
AB  - Hydatid disease, although endemic mostly in sheep-farming countries, remains a
      public health issue worldwide, involving mainly the liver. Intrabiliary rupture
      is the most frequent complication of the hepatic hydatid cyst. Endoscopy is
      advocated, preoperatively, to alleviate obstructive jaundice caused by
      intracystic materials after a frank rupture and is also a useful and well
      established adjunct in locating postoperative biliary fistulas. Endoscopic
      retrograde cholangiography with sphincterotomy has been successful as the sole
      and definitive means of treatment of intrabiliary ruptured hydatid cysts. A case
      of an elderly woman with frank rupture is presented, where the rupture was
      definitively managed endoscopically in conjunction with sphincterotomy to remove
      the intrabiliary obstructive daughter cysts and to achieve decontamination of the
      biliary tree. Endoscopic retrograde cholangiography provided an excellent
      diagnostic and therapeutic modality in the present case and, thus, it should be
      considered as definitive treatment in similar cases especially if surgical risk
      is anticipated to be high.

PMID- 17431517
TI  - Analysis of wave functions for open-shell molecules.
AB  - During the past decade we have looked at several ways to track the distribution
      of unpaired electrons during chemical reactions and in different spin states.
      These methods were inspired by our previous work on singlet di-radicals where the
      spin density is zero yet there are clearly singly occupied orbitals. More
      recently we have been concerned with analysis of wave functions for single
      molecule magnets. This review discusses the mathematical framework by which open
      shell systems can be described, in addition to methods that extract the
      effectively unpaired electron density, the spin state of atoms in a molecule, and
      other useful properties from a molecular wave function. Some of the difficulties
      associated with using broken spin Slater determinants to evaluate the exchange
      coupling parameters in the Heisenberg Hamiltonian are also mentioned.

PMID- 17431518
TI  - Distance measurements on spin-labelled biomacromolecules by pulsed electron
      paramagnetic resonance.
AB  - The biological function of protein, DNA, and RNA molecules often depends on
      relative movements of domains with dimensions of a few nanometers. This length
      scale can be accessed by distance measurements between spin labels if pulsed
      electron paramagnetic resonance (EPR) techniques such as electron-electron double
      resonance (ELDOR) and double-quantum EPR are used. The approach does not require
      crystalline samples and is well suited to biomacromolecules with an intrinsic
      flexibility as distributions of distances can be measured. Furthermore,
      oligomerization or complexation of biomacromolecules can also be studied, even if
      it is incomplete. The sensitivity of the technique and the reliability of the
      measured distance distribution depend on careful optimization of the experimental
      conditions and procedures for data analysis. Interpretation of spin-to-spin
      distance distributions in terms of the structure of the biomacromolecules
      furthermore requires a model for the conformational distribution of the spin
      labels.

PMID- 17431519
TI  - The spin coupling in the diiron complex [Fe2(hpdta)(H2O)3Cl].
AB  - Density functional, multireference configuration interaction, and modified
      valence configuration interaction calculations are used to investigate the
      electronic structure and spin coupling of the dinuclear
      [Fe(2)(hpdta)(H(2)O)(3)Cl] complex (H(5)hpdta = Hydroxypropane-1,3-diamine
      N,N,N',N'-tetraacetic acid). The density functional calculations give evidence of
      both, states with local high-spin iron centres and states with local low-spin
      iron centres, the relative energy of which strongly depends on the functional.
      The splitting of states due to the spin coupling between the high-spin iron
      centres varies by more than a factor of two for different functionals. In an
      attempt to study to what extent it is possible to undertake configuration
      interaction calculations on such binuclear compounds, multireference
      configuration interaction calculations are performed on a
      [Fe(2)(OH)(5)(H(2)O)(3)(NH(3))(2)Cl] model complex. The results show that, when
      correlating only the ten iron 3d orbitals and the four valence orbitals of the
      bridging OH group, the calculated splitting is still by a factor of about 3
      smaller than the value for the splitting inferred from magnetic susceptibility
      measurements. Modified valence configuration interaction calculations are
      performed to approximately take into account the influence of orbital relaxation
      effects of all occupied orbitals in the excited configurations. The exchange
      splitting is significantly increased, but still smaller than the experimental
      value.

PMID- 17431520
TI  - Quintuple-zeta quality coupled-cluster correlation energies with triple-zeta
      basis sets.
AB  - The explicitly-correlated coupled-cluster method CCSD(T)(R12) is extended to
      include F12 geminal basis functions that decay exponentially with the
      interelectronic distance and reproduce the form of the average Coulomb hole more
      accurately than linear-r(12). Equations derived using the Ansatz 2 strong
      orthogonality projector are presented. The convergence of the correlation energy
      with orbital basis set for the new CCSD(T)(F12) method is studied and found to be
      rapid, 98% of the basis set limit correlation energy is typically recovered using
      triple-zeta orbital basis sets. The performance for reaction enthalpies is
      assessed via a test set of 15 reactions involving 23 molecules. The title
      statement is found to hold equally true for total and relative correlation
      energies.

PMID- 17431521
TI  - Allylic hydrogen abstraction II. H-abstraction from 1,4 type polyalkenes as a
      model for free radical trapping by polyunsaturated fatty acids (PUFAs).
AB  - Unsaturated radicals, containing different number of delocalized electrons, are
      formed via H-atom abstractions with CH(3), iso-C(3)H(7), OOH and OH radicals from
      (Z,Z) and (E,E)-hepta-2,5-dienes. These reactions and the relative stability of
      the different allyl-type radicals formed, were studied within the BH&HLYP method,
      using a 6-311+G(3df,2p) basis set, as well as within the G3MP2 level of theory on
      BH&HLYP/6-31G(d) geometries. The biallyl type radicals (involving 5 electrons
      delocalized on 5 carbon atoms) are more stable, by about 47.6 +/- 0.4 kJ mol(-1),
      than monoallyl type radicals (which involve 3 electrons delocalized on 3 carbon
      atoms). Three types of the H-atom abstractions were distinguished: direct H
      abstraction with CH(3), indirect abstraction with a higher barrier height with
      iso-C(3)H(7), OOH and a non-direct quasi-barrierless H-abstraction with OH
      radicals. These observations were also confirmed by the activation entropy versus
      activation enthalpy as well as the Evans-Polanyi's plots. The OOH-hepta-2,5-diene
      complexes are found to be extremely stable (from -19.6 to 22.3 kJ mol(-1)). The
      room temperature rate constants were calculated with transition state theory.
      Formations of monoallyl and biallyl radicals through H-abstraction with OH are
      fast; the calculated rate constants range from 5.84 x 10(-11) to 1.92 x 10(-9)
      cm(3) molecule(-1) s(-1) at room temperature. These reactions may play a key role
      in the "very low temperature combustion" like biological oxidations.

PMID- 17431522
TI  - On the quantitative molecular analysis of electronic energy transfer within donor
      acceptor pairs.
AB  - An extended Forster theory (EFT) on electronic energy transfer is presented for
      the quantitative analysis of time-resolved fluorescence lifetime and
      depolarisation experiments. The EFT, which was derived from the stochastic
      Liouville equation, yields microscopic information concerning the reorientation
      correlation times, the order parameters, as well as inter chromophoric distances.
      Weakly interacting donor and acceptor groups, which reorient and interact in a
      pair wise fashion, are considered, under isotropic and anisotropic conditions.
      For the analysis of experiments it is shown that not only do we need to consider
      the orientational distributions of the transition dipoles, but the internal
      reorienting molecular dynamics within the pair which is of even greater
      importance. The latter determines the shape as well as the rate of the observed
      donor fluorescence and depolarisation decays, which are most often not mono
      exponential functions. It is shown that the commonly used Forster theory is a
      special case of the EFT. Strategies are presented for applying the EFT, which
      makes use of Brownian dynamics simulation.

PMID- 17431523
TI  - Using gamma distributions to predict self-diffusivities and density of states of
      fluids confined in carbon nanotubes.
AB  - The density of states of rare gas atoms confined in carbon nanotubes is analyzed
      using a recently proposed model based on gamma distributions [Krishnan and
      Ayappa, J. Chem. Phys., 124 144503 (2006)]. The inputs into the model are the 2nd
      and 4th frequency moments that are obtained from molecular dynamics simulations.
      The predicted density of states, velocity autocorrelation functions and self
      diffusivities are compared with those obtained from molecular dynamics
      simulations, for different nanotube loadings and temperatures. All results are
      reported for argon confined in a (16,16) carbon nanotube. The model predictions
      are extremely accurate at intermediate reduced densities of rhosigma(3) = 0.3,
      0.4, where the majority of the self-diffusivity predictions lie within 10% of the
      simulation results. Since the frequency moments can be also obtained from Monte
      Carlo simulations, the study suggests an alternate route to the system dynamics
      of strongly confined fluids.

PMID- 17431524
TI  - Separable cooperative and localized translational motions of water confined by a
      chemically heterogeneous environment.
AB  - We report quasi-elastic neutron scattering experiments at two resolutions that
      probe timescales of picoseconds to nanoseconds for the hydration dynamics of
      water, confined in a concentrated solution of N-acetyl-leucine-methylamide
      (NALMA) peptides in water over a temperature range of 248 K to 288 K. The two
      QENS resolutions used allow for a clean separation of two observable
      translational components, and ultimately two very different relaxation processes,
      that become evident when analyzed under a combination of the jump diffusion model
      and the relaxation cage model. The first translational motion is a localized beta
      relaxation process of the bound surface water, and exhibits an Arrhenius
      temperature dependence and a large activation energy of approximately 8 kcal mol(
      1). The second non-Arrhenius translational component is a dynamical signature of
      the alpha-relaxation of more fluid water, exhibiting a glass transition
      temperature of approximately 116 K when fit to the Volger Fulcher Tamman
      functional form. These peptide solutions provide a novel experimental system for
      examining confinement in order to understand the dynamical transition in bulk
      supercooled water by removing the unwanted interface of the confining material on
      water dynamics.

PMID- 17431525
TI  - A crossed molecular beam study on the formation of hexenediynyl radicals
      (H(2)CCCCCCH; C(6)H(3) (X(2)A')) via reactions of tricarbon molecules,
      C(3)(X(1)Sigma(g)(+)), with allene (H(2)CCCH(2); X(1)A(1)) and methylacetylene
      (CH(3)CCH; X(1)A(1)).
AB  - Crossed molecular beams experiments have been utilized to investigate the
      reaction dynamics between two closed shell species, i.e. the reactions of
      tricarbon molecules, C(3)(X(1)Sigma(g)(+)), with allene (H(2)CCCH(2); X(1)A(1)),
      and with methylacetylene (CH(3)CCH; X(1)A(1)). Our investigations indicated that
      both these reactions featured characteristic threshold energies of 40-50 kJ mol(
      1). The reaction dynamics are indirect and suggested the reactions proceeded via
      an initial addition of the tricarbon molecule to the unsaturated hydrocarbon
      molecules forming initially cyclic reaction intermediates of the generic formula
      C(6)H(4). The cyclic intermediates isomerize to yield eventually the acyclic
      isomers CH(3)CCCCCH (methylacetylene reaction) and H(2)CCCCCCH(2) (allene
      reaction). Both structures decompose via atomic hydrogen elimination to form the
      1-hexene-3,4-diynyl-2 radical (C(6)H(3); H(2)CCCCCCH). Future flame studies
      utilizing the Advanced Light Source should therefore investigate the existence of
      1-hexene-3,4-diynyl-2 radicals in high temperature methylacetylene and allene
      flames. Since the corresponding C(3)H(3), C(4)H(3), and C(5)H(3) radicals have
      been identified via their ionization potentials in combustion flames, the
      existence of the C(6)H(3) isomer 1-hexene-3,4-diynyl-2 can be predicted as well.

PMID- 17431526
TI  - A new approach to studying aqueous reactions using diffuse reflectance infrared
      Fourier transform spectrometry: application to the uptake and oxidation of SO2 on
      OH-processed model sea salt aerosol.
AB  - Diffuse reflectance infrared Fourier transform spectrometry (DRIFTS) is a
      powerful technique for analyzing solid powders and for following their reactions
      in real time. We demonstrate that it can also be applied to studying the uptake
      and reactions of gases in liquid films. Within the DRIFTS cell, a 10%(w/w)
      mixture of MgCl(2) x 6H(2)O in NaCl was equilibrated with air at 50% RH, which is
      above the deliquescence point of the magnesium salt but below that of NaCl. This
      mixture of NaCl coated with an aqueous magnesium chloride solution was then
      reacted with gas phase OH to generate hydroxide ions via a previously identified
      interface reaction. This treatment, hereafter referred to as OH-processing, was
      sufficient to convert some of the magnesium chloride to Mg(OH)(2) and
      Mg(2)(OH)(3)Cl x 4H(2)O, making the aqueous film basic and providing a reservoir
      of alkalinity. Subsequent addition of SO(2) to the basic processed mixture
      resulted in its uptake and conversion to sulfite which was measured by FTIR. The
      sulfite was simultaneously oxidized to sulfate by HOCl/OCl(-) that was formed in
      the initial OH-processing of the salt. Further uptake and oxidation of SO(2) in
      the aqueous film took place when the salt was subsequently exposed to O(3). These
      studies demonstrate that DRIFTS can be used to study the chemistry in liquid
      films in real time, and are consistent with the hypothesis that the reaction of
      gaseous OH with chloride ions generates alkalinity that enhances the uptake and
      oxidation of SO(2) under these laboratory conditions.

PMID- 17431527
TI  - Synergistic effect of dicarbollide anions in liquid-liquid extraction: a
      molecular dynamics study at the octanol-water interface.
AB  - We report a molecular dynamics study of chlorinated cobalt bis(dicarbollide)
      anions [(B(9)C(2)H(8)Cl(3))(2)Co](-)"CCD(-)" in octanol and at the octanol-water
      interface, with the main aim to understand why these hydrophobic species act as
      strong synergists in assisted liquid-liquid cation extraction. Neat octanol is
      quite heterogeneous and is found to display dual solvation properties, allowing
      to well solubilize CCD(-), Cs(+) salts in the form of diluted pairs or oligomers,
      without displaying aggregation. At the aqueous interface, octanol behaves as an
      amphiphile, forming either monolayers or bilayers, depending on the initial state
      and confinement conditions. In biphasic octanol-water systems, CCD(-) anions are
      found to mainly partition to the organic phase, thus attracting Cs(+) or even
      more hydrophilic counterions like Eu(3+) into that phase. The remaining CCD(-)
      anions adsorb at the interface, but are less surface active than at the
      chloroform interface. Finally, we compare the interfacial behavior of the
      Eu(BTP)(3)(3+) complex in the absence and in the presence of CCD(-) anions and
      extractant molecules. It is found that when the CCD(-)'s are concentrated enough,
      the complex is extracted to the octanol phase. Otherwise, it is trapped at the
      interface, attracted by water. These results are compared to those obtained with
      chloroform as organic phase and discussed in the context of synergistic effect of
      CCD(-) in liquid-liquid extraction, pointing to the importance of dual solvation
      properties of octanol and of the hydrophobic character of CCD(-) for synergistic
      extraction of cations.

PMID- 17431528
TI  - Virtual reality in mental health : a review of the literature.
AB  - BACKGROUND: Several virtual reality (VR) applications for the understanding,
      assessment and treatment of mental health problems have been developed in the
      last 10 years. The purpose of this review is to outline the current state of
      virtual reality research in the treatment of mental health problems. METHODS:
      PubMed and PsycINFO were searched for all articles containing the words "virtual
      reality". In addition a manual search of the references contained in the papers
      resulting from this search was conducted and relevant periodicals were searched.
      Studies reporting the results of treatment utilizing VR in the mental health
      field and involving at least one patient were identified. RESULTS: More than 50
      studies using VR were identified, the majority of which were case studies.
      Seventeen employed a between groups design: 4 involved patients with fear of
      flying; 3 involved patients with fear of heights; 3 involved patients with social
      phobia/public speaking anxiety; 2 involved people with spider phobia; 2 involved
      patients with agoraphobia; 2 involved patients with body image disturbance and 1
      involved obese patients. There are both advantages in terms of delivery and
      disadvantages in terms of side effects to using VR. Although virtual reality
      based therapy appears to be superior to no treatment the effectiveness of VR
      therapy over traditional therapeutic approaches is not supported by the research
      currently available. CONCLUSIONS: There is a lack of good quality research on the
      effectiveness of VR therapy. Before clinicians will be able to make effective use
      of this emerging technology greater emphasis must be placed on controlled trials
      with clinically identified populations.

PMID- 17431530
TI  - Abstracts of the 34th European Symposium on Calcified Tissues, 5-9 May 2007,
      Copenhagen, Denmark.

PMID- 17431529
TI  - Number and proliferative capacity of human mesenchymal stem cells are modulated
      positively in multiple trauma patients and negatively in atrophic nonunions.
AB  - Mesenchymal stem cells (MSCs) participate in regenerative osteogenesis by
      generating bone-forming cells. To examine the proliferative capacity of MSC
      populations from bone marrow and their relationship to trauma severity (multiple
      trauma, monofracture, atrophic nonunion), we quantified colony properties of
      human MSCs in vitro. Serum levels of mediators associated with bone formation
      were also assessed. Fifty-five individuals were enrolled in this study (13
      multiple trauma patients, 15 patients with monofracture, 20 patients with
      atrophic nonunions, 7 healthy volunteers). The colony forming unit-fibroblast
      (CFU-F) assay was used to quantify total colony number, mean cell density per
      colony, and mean colony area. MSC phenotype was established using flow cytometry
      and osteogenic differentiation. MSCs obtained from multiple-trauma patients
      yielded the highest reservoir. Significant differences in colony numbers of MSCs
      in female subjects were found between multiple-trauma patients (mean +/- SD 48 +/
      21 CFU-F/culture) and healthy volunteers (18.7 +/- 3.3 CFU-F/culture, P < 0.05),
      patients with monotrauma (15 +/- 10 CFU-F/culture, P < 0.05), and patients with
      atrophic nonunions (6.3 +/- 4.1 CFU-F/culture, P < 0.05). In male participants,
      significant differences were found between patients with nonunions (14 +/- 14 CFU
      F/culture) and healthy volunteers (54 +/- 17 CFU-F/culture, P < 0.05) as well as
      multiple-trauma patients (59 +/- 25 CFU-F/culture, P < 0.05). The highest
      proliferative capacity (cell density) was seen in multiple-trauma patients. These
      data suggest that trauma severity and gender affect the reservoir and
      proliferation capacity of bone marrow-derived MSCs.

PMID- 17431532
TI  - Relationship between vascular calcification and bone mineral density in the Old
      order Amish.
AB  - Vascular calcification and osteoporosis are common age-related processes that are
      influenced by both genetic and nongenetic factors. Whether common genes underlie
      these processes is not known. We measured coronary artery calcification (CAC),
      aortic calcification (AC), and bone mineral density (BMD) in 682 men and women
      from large Old-Order Amish families. We assessed the heritabilities of these
      traits and then evaluated, using variance decomposition procedures, whether
      variation in the traits was influenced by a common set of genes (i.e.,
      pleiotropy). Significant heritabilities were detected for BMD of the femoral neck
      and spine (0.65, 0.63) and CAC and AC (0.43, 0.42). Mean BMD did not differ
      significantly across quartiles of either CAC or AC in either sex. In neither the
      total group nor any single subgroup (men, women, postmenopausal women) did any of
      the genetic or environmental correlations between BMD and vascular calcification
      achieve statistical significance. However, subjects with a history of
      cardiovascular disease (CVD) events had significantly lower BMD at the femoral
      neck compared to subjects who reported no prior history of CVD (age-, sex-, body
      mass index-, and family structure-adjusted P = 0.003). We detected no evidence
      for shared genes affecting the joint distribution of bone and vascular
      calcification. However, our results do reveal a lower BMD in subjects with a
      prior history of CVD in the Old-Order Amish.

PMID- 17431533
TI  - Glomerular filtration rate is a major determinant of the relationship between 25
      hydroxyvitamin D and parathyroid hormone.
AB  - The reference range for 25-hydroxyvitamin D (25-OHD) remains uncertain, and it is
      not clear as to whether interpretation of circulating 25-OHD would be aided by
      simultaneous measurement of serum parathyroid hormone (PTH). We wanted to define
      the level of serum 25-OHD associated with a raised serum PTH and to examine the
      determinants of the relationship between serum 25-OHD and serum PTH
      concentration. We retrospectively examined data for patients who had a 25-OHD
      measurement and other biochemical variables over a 12-month period in our center.
      We found that 28% of patients had a serum 25-OHD level below 50 nmol/L and serum
      PTH level in the normal reference range, whereas 24% had a serum 25-OHD level
      below 50 nmol/L with a serum PTH value above the normal reference range. At a
      serum 25-OHD level of 80 nmol/L, 1.5% had an elevated serum PTH and, at 50
      nmol/L, 8% had raised serum PTH. Further examination showed that for patients
      with low serum 25-OHD, low glomerular filtration rate (GFR) was a major
      determinant of the PTH response. These data confirm an inverse correlation
      between serum 25-OHD and serum PTH. Minimal numbers of patients (1.5% of the
      study group) have a raised serum PTH at a serum 25-OHD level of 80 nmol/L. GFR is
      a major determinant of the PTH response to decreasing serum levels of 25-OHD.

PMID- 17431534
TI  - Management of persistent groin pain after transobturator slings.
AB  - Prolonged groin pain after transobturator tape is uncommon. Three women reported
      groin pain that had not improved by 3 months postoperatively. Combined steroid
      and local anesthetic was effective for pain relief in all patients. The
      differential diagnosis of persistent groin pain after transobturator tape
      includes adductor muscle strain, osteitis pubis, obturator/groin abscess,
      structural adhesions, and inflammation, edema or nerve entrapment of the anterior
      branch of the obturator nerve. No side effects of treatment were noted. Patients
      that do not respond to local injection may require mesh dissection and excision.

PMID- 17431535
TI  - Leiomyoma in the Retzius space: a rare cause for voiding difficulties.
AB  - A 54-year-old woman with voiding difficulties was referred to our department. She
      complained about a slow urine stream, hesitancy, straining when voiding and the
      feeling of incomplete emptying. The gynaecological examination revealed a 4x3 cm
      pelvic tumour. The tumour was well circumscribed in the retropubic space between
      the symphysis and the bladder neck sonographically and by magnetic resonance
      imaging and was closed off from neighbouring structures. After removal of the
      tumour, the voiding problems were reversed, and the patient has remained
      asymptomatic. The histological examination showed a leiomyoma with high
      vascularisation. This case report showed that retropubic tumours can obstruct the
      urethra and cause voiding dysfunctions. Consequently, this needs to be considered
      in the differential diagnosis.

PMID- 17431536
TI  - Six months post-operative clinical and 24 hour post-operative MRI examinations
      after nucleoplasty with radiofrequency energy.
AB  - BACKGROUND: Minimally invasive techniques are gaining popularity for the
      treatment of discogenic low-back pain. Nucleoplasty is a relatively new procedure
      that uses radiofrequency energy to disintegrate and evacuate the disc material.
      The purpose of this study is to examine the early post-operative radiological
      changes after lumbar nucleoplasty and to assess the short-term effects of this
      procedure on discogenic lower back pain and leg pain. METHODS: Twenty nine
      patients between the ages of 32 and 59 years (mean 44.14, SD 7.11 years) were
      included in the study. Visual Analogue Scale (VAS) scores of the patients were
      recorded in the pre-operative period and 24 hours, 3 months and 6 months after
      the procedure. Additionally, pre-operative and post-operative lumbar magnetic
      resonance imaging (MRI) examinations of these patients were compared. FINDINGS:
      The mean pre-operative VAS score was 6.95 (range 3.0-10.0, SD 1.87) and the mean
      post-operative VAS scores at 24 hours, 3 months and 6 months were 2.46 (range 0
      8.0, SD 2.07), 4.0 (range 0-10.0, SD 3.09) and 4.53 (range 0-10.0, SD 3.6),
      respectively. There were statistically significant reductions (p < 0.001) in VAS
      scores for all post-operative time points when compared to pre-operative values.
      Nucleoplasty did not produce obvious changes at least on the early post-operative
      MRI examination. CONCLUSIONS: Although, nucleoplasty appeared to be a safe
      minimally invasive procedure, the value of this new technique for the treatment
      of discogenic low-back pain remains as yet unproven. Further randomised placebo
      controlled studies with longer follow-up are needed to elucidate the effects of
      nucleoplasty on discogenic low back and leg pain.

PMID- 17431537
TI  - Cosmetic and radiological outcome following the use of synthetic hydroxyapatite
      porous-dense bilayer burr-hole buttons.
AB  - BACKGROUND: Cranial neurosurgical procedures utilising burr-holes lead to
      development of cosmetically unacceptable puckered scars on the scalp over burr
      hole sites. Ceramics, especially Hydroxyapatite (HA) are good bone substitutes
      owing to their biocompatibility and osteoconduction i.e. ability to lay down bone
      over the implant by fibrovascular invasion and later bone formation. The Sree
      Chitra Tirunal Institute for Medical Sciences and Technology in India has
      pioneered research in this direction and has developed a unique porous-dense
      bilayer HA burr-hole button. This study evaluates the safety, cosmetic effect, as
      well as the radiological outcome following implantation of these bilayer HA
      buttons. METHOD: Sixty-five HA buttons were implanted in 22 patients who
      underwent cranial neurosurgical procedures at the Sree Chitra Tirunal Institute
      for Medical Sciences and Technology. We assessed the cosmetic outcome (absence of
      puckered scar over burr hole sites, absence of allergic reactions or infections
      associated with the implant) as well as the radiological outcome with X-rays at
      specified intervals and looked for interference in the postoperative neurological
      imaging due to the implants. RESULTS: There were no adverse events related to the
      HA buttons in the form of allergic reactions or infections. The implants
      persisted as radio-dense opacities on skull X-rays of recipients for up to two
      years. It did not lead to artefacts on postoperative CT or MR imaging of the
      brain. In particular, the HA buttons could be subtracted on Digital Subtraction
      Angiography and did not obstruct visualisation of the cerebral vasculature.
      CONCLUSION: The bi-layer porous-dense HA buttons are useful in preventing
      cosmetic defects over burr-hole sites on the scalp after cranial neurosurgical
      procedures. It does not interfere with current radiological imaging methods in
      the postoperative phase.

PMID- 17431538
TI  - Humanitarian medicine: what is the role of neurosurgery?

PMID- 17431539
TI  - Tilt angle of lipid acyl chains in unilamellar vesicles determined by
      ellipsometric light scattering.
AB  - Ellipsometric light scattering (ELS) at room temperature is applied to
      unilamellar vesicles (approximately 50 nm radius) of 1,2-Dipalmitoyl-sn-glycero-3
      phosphocholine (DPPC) in the gel phase and of 1,2-Dioleoyl-sn-glycero-3
      phosphocholine (DOPC) in the liquid-crystaline phase. A high sensitivity of this
      technique to the local anisotropy is found. From the resulting local
      birefringence, a lower limit of (29 +/-0.5) degrees for the average tilt angle of
      the lipid chains of DPPC with respect to the membrane normal is estimated. This
      tilt angle value is slightly lower than literature values for the tilt angle in
      oriented lipid multi-bilayers on solid substrates.

PMID- 17431540
TI  - Segregation in desiccated sessile drops of biological fluids.
AB  - It is shown here that concurrence between advection and diffusion in a drying
      sessile drop of a biological fluid can produce spatial redistribution of albumen
      and salt. The result gives an explanation for the patterns observed in the dried
      drops of the biological fluids.

PMID- 17431541
TI  - Intraspecific morphological and genetic differentiation in Scrophularia grayana
      (Scrophulariaceae).
AB  - Scrophularia grayana, which is distributed throughout northern Japan and
      Sakhalin, and its locally endemic variety var. grayanoides, have been examined
      morphometrically and genetically. Principal-component analysis using a total of
      26 morphological characteristics revealed that these taxa are morphologically
      differentiated, but that the difference is not distinct. These two taxa have the
      same number of chromosomes in the somatic cells, 2n = 94, suggesting that ploidal
      level difference is not relevant to their divergence. The distributions of the
      taxa are adjoining in the north of Japanese mainland Honshu. Nevertheless,
      principal-coordinate analysis using putative 112 ISSR loci indicated they are
      genetically very distinct. Many taxon-specific alleles were found, and many of
      the alleles were fixed in each taxon. This genetic information suggests that a
      relatively long time has passed since the taxa became differentiated and that
      gene flow has rarely occurred between them, although morphological similarity has
      been maintained, probably because of natural selective forces.

PMID- 17431542
TI  - Retrospective analysis of the efficacy and tolerability of levetiracetam in
      patients with metastatic brain tumors.
AB  - Seizures are a common complication of metastatic brain tumors (MBT), affecting
      approximately 27-50% of all patients during the course of their illness.
      Treatment of tumor-induced seizures is often inadequate with traditional
      antiepileptic drugs (AED) due to a variety of factors, including activation of
      glutamatergic NMDA receptors, alterations of neuronal input pathways, and tumor
      growth. Levetiracetam (LEV) is a 2nd generation non-enzyme inducing AED with a
      novel mechanism of action, binding to neuronal synaptic vesicle protein SV2A,
      that has been previously shown to reduce seizure activity in patients with
      primary brain tumors. Due to its unique mechanism of action, it has been
      postulated that LEV may also be effective in controlling seizures from MBT. A
      retrospective chart review was performed of all Neuro-Oncology Center patients
      with MBT who had received LEV for seizure control. Thirteen patients were
      reviewed with a median age of 55.1 years (range: 34-70). Six patients had breast
      cancer, five had lung cancer, and two had melanoma. LEV was used as an add-on AED
      in seven patients (54%) and as monotherapy in six patients (46%), with a median
      dose of 1,000 mg/day (range: 500-3,000). The baseline median seizure frequency
      was one ictal event every other day. After the addition of LEV, the median
      seizure frequency was reduced to 0 per week. The seizure frequency was reduced to
      less than 50% of the pre-LEV baseline in 100% of patients (P=0.0002, Sign test),
      with 10 patients (77%; confidence interval: 46-95%) noting complete seizure
      control. The most common adverse event was somnolence and headache, noted in 3 of
      13 patients (23%). LEV was very effective and well tolerated in MBT patients with
      seizures and should be considered for add-on therapy or as a substitute AED for
      monotherapy.

PMID- 17431543
TI  - Clinical analysis of paraneoplastic encephalitis associated with ovarian
      teratoma.
AB  - BACKGROUND: Recently, paraneoplastic encephalitis associated with ovarian
      teratoma has been described and related to an autoantibody. METHODS: We describe
      four patients with ovarian teratoma-associated encephalitis (OTE) and compared
      their clinical pictures with those of 17 previously reported patients with OTE.
      RESULTS: Clinically, OTE was characterized by the development of acute prominent
      psychiatric symptoms (20 of 21 patients), seizures (15 of 21 patients), and
      central hypoventilation (13 of 21 patients). Our patients had hypersalivation
      (three patients) and cardiac conduction problems (all patients); hypothermia was
      present in one patient. The mean time from the onset of OTE to tumor diagnosis
      was 19.6+/-22.1 weeks. Ventilatory support was required for 54.9+/-25.4 days on
      average. The white blood cell count in cerebrospinal fluid was 55.1+/-61.2/mm3.
      Twelve patients showed abnormalities on cranial MRI, involving areas such as the
      temporal regions (seven patients) or brainstem (four patients). In addition to
      tumor resection, 17 patients received some type of immunotherapy: 17 patients
      received corticosteroids, 10 received intravenous immunoglobulins, two received
      cyclophosphamide, seven received plasma exchange. Eighteen patients with OTE had
      neurological improvement, including 11 with full recovery. CONCLUSIONS: OTE
      presents with cardiac conduction problems and hypersalivation in addition to
      psychiatric symptoms, seizures, and central hypoventilation.

PMID- 17431544
TI  - Prognosis in patients with anaplastic oligoastrocytoma is associated with
      histologic grade.
AB  - BACKGROUND: Anaplastic oligoastrocytomas (AOA) are relatively uncommon high-grade
      gliomas. While oligodendroglial elements are thought to be associated with better
      outcomes, the magnitude of the difference is not clear. METHODS: Between 1980 and
      1999, Mayo Clinic and the NCCTG conducted 10 trials of radiation therapy and
      chemotherapy in adults with newly-diagnosed high-grade gliomas. All pathology
      slides were reviewed by one of the authors (BWS or CG). We grouped patients by
      cell type and grade, compared survival distributions by the log-rank statistic,
      and performed multiple variable analyses. RESULTS: Of 1368 patients, 68 (5%) had
      AOA, including 21 Grade 3 (OA3) and 47 grade 4 (OA4), 153 (11%) had anaplastic
      astrocytoma (AA), and 1147 (84%) had glioblastoma multiforme (GBM). Patients with
      OA3 survived significantly longer than those with OA4 (P=0.0001) or AA
      (P=0.0044). Patients with OA4 lived significantly longer than those with GBM
      (P=0.0005). The same differences were noted for PFS. Prognostic factors for
      survival identified by multiple variable analysis were histology, age, ECOG
      performance score, and extent of surgical resection, but not treatment
      administered. CONCLUSIONS: Patients with anaplastic oligoastrocytoma have
      distinct outcomes based upon grade (OA3 vs. OA4) and in comparison with pure
      astrocytoma (AA or GBM). Future trials which include more than one histologic
      entity need to report results by cell type and grade and account for the varying
      prognoses in interpreting treatment outcomes.

PMID- 17431545
TI  - Differential effect of surgery and radiotherapy on neurocognitive functioning and
      health-related quality of life in WHO grade I meningioma patients.
AB  - BACKGROUND: Potential treatment-related neurotoxicity and the indolent course of
      the disease mainly feed the controversy concerning the optimal timing of surgery
      and radiotherapy in meningioma patients. OBJECT: To quantify the additional
      negative effects of conventional radiotherapy compared to surgery alone on
      neurocognitive functioning and health-related quality of life (HRQOL) in patients
      with WHO grade I meningiomas. METHODS: Neurocognitive functioning and HRQOL
      (SF36, EORTC-BCM20) were assessed in consecutive patients (1999-2005) with WHO
      grade I meningiomas at least 1 year after surgical treatment in two centers for
      brain tumor patients. Subsequently, we selected all patients who underwent
      surgery and conformal external beam fractioned radiotherapy (n=18) and matched
      these patients for age, sex, and educational level with the same number of
      patients who had had surgery only (n=18), as well as with the same number of
      healthy controls. RESULTS: No significant differences in neurocognitive
      functioning were found between the two meningioma patient groups; however, even
      meningioma patients who were treated with surgery only had a significantly lower
      neurocognitive functioning than healthy controls. Meningioma patients who were
      treated with surgery and radiotherapy had significantly lower HRQOL scores than
      meningioma patients who were treated with surgery only, who had HRQOL ratings
      comparable with healthy controls; these differences, however, disappeared after
      correction for the duration of disease. CONCLUSIONS: In contrast with
      conventional thinking, long-term neurocognitive functioning was significantly
      impaired in our meningioma patients. Additional radiotherapy following surgery,
      however, does not have additional deleterious effects on neurocognitive outcome
      in these patients.

PMID- 17431546
TI  - Atypical teratoid/rhabdoid tumor arising in the setting of a pleomorphic
      xanthoastrocytoma.
AB  - We present a case of a 23-year-old man with a tumor containing glial and rhabdoid
      elements where the former had features of a pleomorphic xanthoastrocytoma (PXA)
      and the latter had the immunophenotype and genetic profile of an atypical
      rhabdoid/teratoid tumor. The patient presented with a short history of raised
      intracranial pressure with rapid deterioration in sensorium. He had a poor
      outcome despite surgery and radiotherapy. We report this case because of its
      unusual presentation in adulthood and its occurrence in association with a PXA.
      We speculate that the PXA was a quiescent tumor and that the secondary genetic
      alterations, including inactivation of the INI1 gene led to clinical progression.

PMID- 17431547
TI  - French brain tumor data bank: methodology and first results on 10,000 cases.
AB  - This work aims to prospectively record all primary central nervous system tumors
      (PCNST), in France, for which histological diagnosis is available. The objectives
      are to create a national registry and a network to perform epidemiological
      studies, to implement clinical and basic research protocols, and to harmonize the
      healthcare of patients affected by PCNST. Following a feasibility study,
      including an estimate of the gross incidence of PCNST (15.8/100,000 person-years)
      in France, all French neuropathology and neurosurgery departments decided to
      participate in the program. For each patient, the neurosurgeon and the
      neuropathologist complete a data file containing socio-demographic, clinical,
      radiologic and anatomopathologic information. The Tumor Registry from Herault is
      authorized to compile the data files with personal identifiers. In 2.5 years,
      10,093 cases of newly diagnosed PCNST have been recorded. Tumor resections were
      performed in 75.3%, while biopsies accounted for 24.7%. Histological diagnoses
      included glioma (49.6%), other neuroepithelial tumors (3.8%), meningioma (30.9%),
      neurinoma (8.7%), lymphoma (2.9%) and others (4.1%). Cryopreservation was
      reported for 2,261 PCNST specimens. Clinical and radiological aspects were also
      recorded. Preliminary results are encouraging and stimulating for the long-term
      goal of creating a National Registry and a National Network for patients affected
      by PCNST. To our knowledge, this is the first European databank dedicated to
      PCNST, with collection of clinical, radiological and histological data (including
      cryopreservation of the specimen). The creation of this registry and this
      database may have major clinical and fundamental implications.

PMID- 17431548
TI  - The role of chemokines and their receptors in uveitis.
AB  - T-cell-dependent immunological events are increasingly being regarded as
      extremely important in the pathogenesis of uveitis. Several studies have also
      shown that macrophages are major effectors of tissue damage in uveitis.
      Neutrophils are also thought to play a central role in the pathogenesis of
      Behcet's disease. Chemokines are a superfamily of 8 to 10-kDa secreted proteins
      that direct the recruitment of leukocytes to sites of inflammation. The specific
      biological effects of chemokines are mediated by a family of seven transmembrane
      spanning G-protein-coupled receptors. Recent studies of animals and humans
      suggest that chemokines and their receptors play a key role in leukocyte
      recruitment into the eye in uveitis. A strategy for blocking chemokines or
      chemokine receptors could be a new approach for treatment of uveitis.

PMID- 17431549
TI  - Expression of foreign proteins in a Vibrio cholerae vaccine strain using the
      stationary phase hemagglutinin/protease promoter.
AB  - The use of the hemagglutinin(HA)/protease promoter and secretion signals to drive
      expression and secretion of a foreign antigen in a live genetically attenuated
      cholera vaccine candidate is demonstrated. A Vibrio cholerae vaccine strain,
      containing a HA/protease-tetanus toxin C fragment (TCF) fusion, produced soluble
      and cell-associated TCF. The fraction of TCF secreted to the culture medium was
      degraded unless expressed in a HA/protease-defective vaccine strain. Comparison
      of the hapA promoter with the strong Tac promoter using quantitative real time
      PCR revealed that at least five times more TCF mRNA was produced when expressed
      from the hapA promoter.

PMID- 17431550
TI  - The NMR structure of the domain II of a chloroplastic NifU-like protein OsNifU1A.
AB  - NifU-like proteins are a highly conserved protein that serves as the scaffold for
      assembly of Fe-S clusters. Chloroplastic NifU-like proteins have tandem NifU like
      domains, named domain I and domain II. Although the amino acid sequences of these
      domains are very similar to each other, the predicted functional region for the
      Fe-S cluster assembly, the CXXC motif, exists only in domain I. The structure of
      the domain II of chloroplastic NifU-like protein OsNifU1A has an alpha-beta
      sandwich structure containing two alpha helices located on one side of the beta
      sheet. The electrostatic surface potential of OsNifU1A domain II is predominantly
      positively charged. Chloroplastic NifU-like proteins are targeted to ferredoxin
      for transferring the Fe-S cluster. The ferredoxin presents an overall negatively
      charged surface, which may evoke an electrostatic association with OsNifU1A
      domain II.

PMID- 17431551
TI  - [Epidural anesthesia].
AB  - In epidural anaesthesia, the anaesthetist injects one or more drugs into the
      epidural space bordering on the spinal dura mater to achieve a "central" and/or
      "neuraxial" block. It is one of the earliest techniques in anaesthesia,
      originally performed exclusively with local anaesthetic agents. Adding other
      drugs and combining epidural with general anaesthesia or adapting the technique
      to the needs of children has extended the list of indications. Continuous
      epidural analgesia is an important tool in postoperative pain management. More
      and more often, the increasing proportion of patients who have comorbidities or
      are permanently taking medication that modulates the clotting system demands that
      the anaesthesiologist balance the individual risks and benefits before inducing
      epidural anaesthesia.

PMID- 17431552
TI  - [Infection control measures and surveillance of patients with ventricular assist
      devices].
AB  - Ventricular assist devices (VAD) are a new routine therapy option for end-stage
      heart failure. However, the incidence of VAD-related infections varies between 20
      and 188% and makes a major contribution to VAD-related morbidity. Therefore,
      optimised infection control policies should be applied to prevent VAD-related
      infections. As to date only a few studies exist investigating particular
      prevention measures for VAD recipients, we have tried to adapt evidence-based
      guidelines. In detail the following preventive measures are discussed: antibiotic
      prophylaxis, endocarditis prophylaxis, dressing technique for the driveline-exit
      site and education of patients and medical staff. A new patient-based
      surveillance system is proposed which reflects the different times since
      implantation of VADs and therefore allows a fair method for interhospital
      comparison.

PMID- 17431553
TI  - [Laparoscopic ultrasound].
AB  - Laparoscopic ultrasound exploration has significantly augmented the range of
      minimally invasive surgery. In particular it is essential for 3D exploration of
      the abdomen for staging. Beyond its diagnostic, purposes laparoscopic ultrasound
      is gaining importance for intraoperative therapeutic support, e. g. imaging of
      the biliary tree during laparoscopic surgery of the bile duct and for navigation
      during radio-frequency ablative or resective interventions on the liver and other
      parenchymatous organs. Compared to other imaging procedures, sonography has still
      the highest potential for further development. The most progress can be expected
      in navigated ultrasound.

PMID- 17431554
TI  - [Subcutaneous emphysema of unusual extent].
AB  - Streptococcus agalactiae, known as a pathogen that causes meningitis and
      septicemia in neonates, emerges as an invasive organism in nonpregnant adults.
      This case report describes the fulminant course of a necrotizing fasciitis (NF)
      with streptococcal toxic shock-like syndrome (STSS) in a 76-year-old diabetic
      patient caused by S. agalactiae, serotype V. Chronic diseases and
      immunodeficiency are considered to be risk factors for the acquisition of group B
      streptococcal disease. Since early surgical treatment in conjunction with
      antimicrobial and intensive care therapy is critical for the outcome of patients
      with NF and/or STSS, clinicians should be aware of invasive S. agalactiae
      infections in adults with subcutaneous emphysema.

PMID- 17431555
TI  - [Transcutaneous ultrasound].
AB  - Preoperative transcutaneous ultrasound allows surgeons to assess the pathology
      directly, thus supplementing clinical examination of the patient. Technical
      advances including power doppler, three-dimensional ultrasound, and the advent of
      ultrasound contrast agents have increased the quality and broadened the
      diagnostic spectrum of ultrasound. This article reviews relevant new aspects of
      transcutaneous ultrasound in the surgical setting.

PMID- 17431556
TI  - [Ultrasound in vascular surgery].
AB  - Diagnosing vascular diseases by ultrasound is of major interest to vascular
      surgeons and now regarded as the primary noninvasive technique. This paper
      presents developments in four different fields: stenoses of the carotid arteries,
      peripheral artery occlusive diseases (PAOD) including surveillance programs,
      diseases of the veins, and abdominal aortic aneurysm. Calculating the extent of a
      carotid artery stenosis is now accurate, but plaque imaging remains complex.
      Examination by ultrasound should precede any invasive techniques in PAOD. Duplex
      surveillance on a routine basis is no longer recommended after infrainguinal
      bypass. In future vascular diseases will be diagnosed primarily by ultrasound.
      Diagnosis of abdominal aneurysm is now absolutely reliable, whereas planning and
      follow-up of endoluminal techniques are quite restricted.

PMID- 17431557
TI  - [Fibrin glue and seroma formation following abdominoplasty].
AB  - BACKGROUND: Seroma formation is one of the most frequent complications following
      abdominoplasty. The effect of intraoperative fibrin sealant on the formation of
      seroma was investigated in patients who had an abdominoplasty. The relevance of
      slow vs accelerated fibrin polymerization was determined. MATERIAL AND METHODS:
      Two different thrombin concentrations (4 IE vs 500 IE thrombin/ml) of fibrin
      sealant were used in two groups of 20 patients each. The control group consisted
      of 20 patients with abdominoplasties without fibrin glue adhesion. RESULTS: The
      group with slow-reacting fibrin sealant (4 IE) had a significantly lower rate of
      seroma formation than both the high concentration fibrin group and controls
      (P<0.032 and P<0.018, respectively). In addition, the amount of postoperative
      drainage was significantly lower in the low-dose group (P<0.000). Patients with
      seroma had a significantly higher weight of resected tissue (P<0.04). The amount
      of postoperative drainage, age, and body/mass index had no significant effect on
      the prevalence of complications. CONCLUSION: The use of slow reacting, low-dose
      fibrin glue demonstrated a protective effect against the formation of seroma
      following abdominoplasty. The amount of postoperative drainage was significantly
      lower.

PMID- 17431558
TI  - [Nihilodermia in psychodermatology].
AB  - "Nihilodermia" refers to a group of difficult "problem" patients in dermatology
      without objective findings but with recurrent symptoms and stubborn demand for
      medical examination. These primary emotional disorders are somatoform disorders,
      but the patients usually strictly deny a psychosocial aspect and expect purely
      somatic treatment. Clinical patterns include pruritus, pain, paresthesias,
      feelings of disfiguration, eco-syndromes, erythrophobia and psychogenic
      pseudoeffluvium. The relevant somatoform disorders in dermatology can be
      differentiated as somatization disorders, hypochondriacal disorders, somatoform
      autonomous disorders, persistent somatoform pain disorders and "other somatoform
      disorders". A precise differential diagnostic division is necessary in order to
      initiate adequate therapy strategies.

PMID- 17431559
TI  - [Epithelial skin tumors].

PMID- 17431561
TI  - [Music therapy in tinnitus: effective supplement to habituation and hearing
      therapy].

PMID- 17431563
TI  - [Impaired wound healing following tonsillectomy].
AB  - Tonsillectomy is one of the most commonly performed surgical procedures in the
      field of otorhinolaryngology. The first tonsillectomy was done about 600 B.C.
      [3]. This operation is indicated for patients with recurrent tonsillitis,
      peritonsillar abscess, hypertrophy or asymmetry of the tonsils. Even though a
      routine procedure, it has a relatively high risk of complications such as post
      operative hemorrhage, infection or impaired wound healing. The reported case
      involves a 20 year old female patient who developed velopharyngeal insufficiency
      as a result of impaired wound healing after tonsillectomy. The patient was
      treated conservatively and is free of discomfort after 2 months.

PMID- 17431562
TI  - [Papillary thyroid carcinoma in a thyroglossal duct cyst: primary tumor or
      metastasis?].
AB  - Thyroglossal duct cysts are the most common anomaly in thyroid development. The
      occurrence of carcinoma in a cyst is reported to be about 1% of cases.
      Histopathological examinations reveal a papillary thyroid carcinoma in about 94%
      of these. We report the case of 38-year-old female having a massive, cervical
      cystic mass over a period of 18 months. An ectopic papillary thyroid carcinoma
      was diagnosed. A total thyoidectomy and bilateral neck dissection were performed.
      This revealed a small thyroid carcinoma and three positive lymphatic nodes.
      Whether the cystic carcinoma is the primary or a metastasis of the thyroid
      carcinomais discussed.

PMID- 17431564
TI  - [Functional anatomy of the larynx from clinical points of view: part II:
      Laryngeal mucous membrane, blood supply, innervation, lymphatic drainage, age
      related changes].
AB  - Diseases of the larynx are of concern not only for ear, nose, and throat
      physicians and phoniatricians but also for other clinicians who treat the larynx
      either conservatively or surgically, including speech therapists, pediatricians,
      anesthetists, oncologists, pulmonologists, radiologists, and general
      practitioners. Based on today's state of knowledge and taking into account our
      own research results of the last years as well as clinical points of view, the
      present contribution gives a short overview of the anatomy and physiology of the
      larynx. Part 2 discusses the functional anatomy of the laryngeal mucous membrane
      (glycoconjugates, mucins, trefoil factor family peptides, antimicrobial
      substances, larynx-associated lymphoid tissue), the vascular supply, innervation,
      and lymphatic drainage, as well as age-related laryngeal changes and their
      effects on swallowing, breathing, and phonation.

PMID- 17431565
TI  - [Functional anatomy of the larynx from clinical viewpoints. Part I: development,
      laryngeal skeleton, joints, insertion structures, musculature].
AB  - ENT specialist and phoniatricians are not the only professionals for whom
      diseases of the larynx occupy centre stage; this applies to those in all fields
      involving conservative or surgical treatment of the larynx, such as speech
      therapists, paediatricians, anaesthetists, oncologists, pulmonologists,
      radiologists and general practitioners. On the basis of current knowledge and
      taking account of results yielded by their own research in recent years and of
      clinical aspects, in this paper the authors give a short overview of basic
      knowledge on the anatomy and physiology of the larynx. Part 1 deals with its
      development and division, the laryngeal skeleton and joints, the insertion
      structures of the vocal folds and the laryngeal musculature and describes new
      insights into the mineralization and ossification of the laryngeal skeleton and
      their implications for phonation, arytenoid subluxation, degenerative joint
      changes and the biomechanics of vocal cord insertion.

PMID- 17431566
TI  - [The treatment of laryngeal movement disorders with botulinum toxin: part 2:
      experience and considerations].
AB  - Laryngeal dystonia (spasmodic dysphonia) is a movement disorder characterised by
      involuntary contractions of the laryngeal muscles involved in vocalisation. The
      introduction of botulinum toxin (BTX) in the treatment of laryngeal dystonia had
      a major clinical impact due to the striking improvement of symptoms. In general,
      BTX can be delivered by percutaneous injection or by the transoral route. The
      subcutaneous method is simple, but the effects of the transoral injection,
      applied through a curved device or by use of a flexible nasolaryngoscope with a
      working channel and visual control, might be more effective. However, for various
      reasons the transoral route does not work in every patient. We report our
      experiences using these different techniques for the monitoring of patients and
      their treatment with botulinum toxin in laryngeal movement disorders.

PMID- 17431567
TI  - [Treatment of laryngeal movement disorders with botulinum toxins: part 1: History
      and mode of action].
AB  - Laryngeal dystonia (spasmodic dysphonia) is a movement disorder characterised by
      involuntary contractions of the laryngeal muscles involved in vocalisation. The
      introduction of botulinum toxin (BTX) in the treatment of laryngeal dystonia had
      a major clinical impact due to the striking improvement of symptoms. Most
      patients with severe types of spasmodic dysphonia are treated with injections of
      botulinum toxin type A. For patients with a resistance against type A toxin there
      is a new hypercleaned type A toxin or type B available. Research on type F toxin
      is also underway. In this article, the history of botulinum toxin, its
      therapeutic activity and possibilities for its use are described.

PMID- 17431568
TI  - [Treatment of patients with aphasia--practical considerations].
AB  - Aphasia often leads to severe restrictions in communicative behaviour and social
      participation. Therapeutic strategies aiming at improving communicative
      competence usually have to be carried out over a long period and may be very
      costly. If prescribed, such therapies will be financed by the health insurance
      systems. Prescriptions, however, must respect the individual needs of a patient
      as well as certain restrictions outlined in insurance guidelines. This can lead
      to problems if the patient's or relatives' wish for therapy is completely or
      partially ignored. Here we discuss the rational for prescribing therapy for
      aphasia patients based on current guidelines and discuss how the patients and
      relatives can be best advised.

PMID- 17431569
TI  - [Basic research on vocal fold dynamics: three-dimensional vibration analysis of
      human and canine larynges].
AB  - BACKGROUND: The understanding of normal and pathological vocal fold dynamics is
      the basis for a pathophysiological motivated voice therapy. Crucial vocal fold
      dynamics concerning voice production occur at the medial part of the vocal fold
      which is seen as the most critical region of mucosal wave propagation. Due to the
      limited size of the larynx the possibilities of laryngeal imaging by endoscopic
      techniques are limited. MATERIAL AND METHODS: This work describes an experimental
      set-up that enables quantification of the entire medial and superior vocal fold
      surface using excised human and in vivo canine larynges. RESULTS: The data
      obtained enable analysis of vocal fold deflections, velocities, and mucosal wave
      propagation. The reciprocal dependencies can be examined and different areas of
      vocal fold dynamics located. The vertical components obscured in clinical
      endoscopy can be visualized. This is not negligible. CONCLUSIONS: In particular
      it is shown that the vertical deflection, which cannot be observed by clinical
      examination, plays an important part in the dynamics and therefore cannot be
      omitted for therapeutic procedures. The theoretically assumed entrainment and
      influence of the two main vibration modes enabling normal phonation is confirmed.

PMID- 17431570
TI  - [Coblation tonsillectomy: a review of the literature].
AB  - BACKGROUND: Controversy surrounds the question of which technique should be
      preferred for tonsillectomy in order to reduce postoperative morbidity in terms
      of pain, bleeding, activity and return to normal diet. This study reviews the
      current literature on coblation tonsillectomy (CTE). MATERIALS AND METHODS: All
      studies published in peer-reviewed journals reporting postoperative morbidity
      following CTE until July 2006 were included in our study. RESULTS: A total of 21
      studies matched our search criteria but there were excluded from further analysis
      because coblation was used only for volume reduction of the tonsils. Reduced
      morbidity was registered in eight studies, two could not identify any difference
      and five studies reported an increased postoperative morbidity. Seven different
      surgical procedures were compared in 17 studies to CTE. The patients were not
      followed-up in four studies and the follow-up exceeded 1 week in nine studies
      only. Wound inspection was performed in four studies and a better wound healing
      reported in two of these, but by the same authors. Postoperative bleeding
      requiring surgical treatment under general anaesthesia occurred with an incidence
      of 0% to 11.5%. Secondary bleeding (>24 h) prevailed in all but two studies.
      Postoperative pain was evaluated in ten studies with conflicting results.
      CONCLUSIONS: The design of the current studies varies in size, age distribution,
      indications for surgery, the surgical techniques compared and follow-up. The
      results are heterogenous and further evidence is still required to show that CTE
      is a safe alternative. Therefore, calculation of cost-effectiveness of a commonly
      performed expensive CTE as a new standard technique is currently impossible.

PMID- 17431571
TI  - [Repeated dual-probe pH monitoring as a diagnostic tool to control therapy for
      laryngopharyngeal reflux].
AB  - OBJECTIVES: The most effective current treatment option for patients suffering
      from laryngopharyngeal reflux (LPR) is the use of proton pump inhibitors (PPIs).
      Compared to other PPIs, esomeprazole seems to provide best 24-h control of
      intragastric acid. However, some patients remain resistant to medical acid
      suppression with PPIs. The aim of this investigation was to identify the number
      of non-responders among patients suffering from LPR being treated by esomeprazole
      40 mg once daily (officially approved maximum dosage). PATIENTS AND METHODS:
      Between June 2004 and January 2006, 27 patients suffering from LPR diagnosed by
      dual-probe pH monitoring were treated with esomeprazole 40 mg once daily. After
      13-54 days (mean 28 days) while still under PPI-treatment, the 24-h pH-study was
      repeated in order to control the effectiveness of therapy. Patients with at least
      a reduction of the reflux area index (RAI) compared to the result before
      treatment were categorized as responders. Furthermore, the number of patients
      with a measurable reduction of proximal reflux episodes under PPI-treatment was
      quantified. RESULTS: Repeated pH monitoring during PPI therapy revealed a
      reduction of the RAI in 22 of 27 patients. Five patients, however, showed a
      higher RAI despite medical treatment (19%). In 13 patients (48%), treatment with
      40 mg esomeprazole once daily reduced the RAI to a normal value (<6.3). In 18 of
      27 patients, the number of proximal reflux episodes has decreased (67%).
      CONCLUSION: In a number of patients suffering from LPR, treatment with
      esomeprazole 40 mg once daily did not provide any measurable proximal acid
      reduction. Repeated pH monitoring during treatment is an adequate diagnostic tool
      to control the therapeutic effect of PPIs objectively and to identify non
      responders at an early point.

PMID- 17431573
TI  - [Chronic HIV infection. Current therapeutic aspects].
AB  - Human immunodeficiency virus (HIV) infection is one of the most prominent health
      care challenges world wide. In Western industrialized countries where common
      access to antiretroviral drugs exists, HIV infection is a well treatable disease
      in the long-term for most patients. However, given the possible evolution of drug
      resistance, the right combination of antiretroviral drugs in first-line therapy
      is crucial for maintaining long-term success. For each individual patient, the
      ideal time to start antiretroviral therapy must be carefully selected. The
      individual risk of progression to acquired immunodeficiency syndrome (AIDS) on
      the one hand, and the risks of long-term toxicity and adherence problems under
      therapy on the other hand must be taken into account. Each patient should be
      counseled according to present treatment guidelines on when and how to start
      HAART, taking into account the surrogate markers CD4-cell count and HIV-RNA as
      well as clinically apparent HIV-associated disease.

PMID- 17431572
TI  - [Treatment of community acquired pneumonia].
AB  - The S3 guidelines for diagnosis and therapy use German epidemiological data to
      set the standards for a risk and degree of severity based treatment of community
      acquired pneumonia (CAP). Over the last few years, a change in pathogen
      epidemiology has been recognized with the significance of staphylococci and
      enterobacteria increasing. CAP is becoming increasingly a disease of the elderly,
      for whom a more broadly effective initial therapy appears to be needed. Resistant
      pathogens play an important role in the course of the disease. For patients with
      a low risk of mortality, a reduction in the length of therapy seems possible. On
      the other hand, the early identification of critically ill patients who require
      treatment with high dose, broad spectrum antibiotics is necessary. Antibiotic
      associated diarrhoea, caused by Clostridium difficile, is a significant
      complication in antibiotic therapy. With the introduction of vaccination against
      Streptococcus pneumoniae for children, a change in the course of the illness and
      an improvement in the resistance situation has been achieved. An update of the S3
      guidelines is intended for 2008 in order to integrate new knowledge into the
      recommendations.

PMID- 17431575
TI  - [Aneurysmal bone cysts. First description of the extensive destruction of the
      upper cervical spine].
AB  - Aneurysmal bone cysts are not counted among the classic malignant tumors,
      although they are destructive locally as blood filled reactive bone lesions.
      Typically, they are found in the metaphysis of the long bones, while
      localizations on the spine are rare. A 16-year-old female patient presented with
      unspecific, progressive neck pain which had been present for half a year. The
      initial x-ray showed no noticeable pathology whatsoever. Subsequently, the
      complete destruction of the first cervical vertebrae was found. The tumor had
      completely infiltrated and completely surrounded the spinal chord. A combined
      approach was used as therapy: resection of the dorsal tumor portion with
      occipitocervical spondylodesis (C0-C4) and postoperative radiation of the
      remaining ventral portions. Currently, the patient is free of complaints and
      recurrence. The differential diagnosis of an aneurysmal bone cyst should also be
      considered in cases of unspecific cervical vertebral complaints in adolescents
      that are not otherwise explainable.

PMID- 17431574
TI  - [Traumatic atlanto-occipital dislocation as part of a complex cervical spine
      injury. Case report in a 12-year-old girl].
AB  - Traumatic atlanto-occipital dislocation (AOD) appears to be an unusual and almost
      universally fatal injury. Although AOD is the cause of death in about 10% of
      fatal cervical spine injuries an increasing number of reports document cases of
      survival following this injury. Improved pre-hospital and in-hospital emergency
      care according to ATLS guidelines that include early cervical spine
      stabilization, effective diagnosis because of improved imaging after trauma
      including whole body multislice CT followed by expeditious reposition and
      adequate immobilization are reasons for this phenomenon. We report the case of a
      12-year-old girl surviving an AOD accompanied by a distraction injury C6/7 with
      unilateral fixed spinal luxation. After a primary attempt at closed reduction and
      external stabilization with a halo vest, the injury was treated by a navigated
      dorsal spondylodesis C0-C1 using the CerviFix rod system and open reposition of
      the remaining subluxation C6/7 with laminar hooks. The literature was reviewed
      for diagnostic possibilities, management and prognosis of AOD.

PMID- 17431576
TI  - [Traumatic rupture of the cardiac auricle after forceful blunt abdominal trauma].
AB  - Rupture of the heart after blunt trauma has been attributed to multiple
      mechanisms. We present a patient in whom massive abdominal blunt trauma leading
      to massive venous return resulted in rupture of the auricle without pericardial
      rupture.

PMID- 17431578
TI  - [Lifestyle, erectile dysfunction, hormones and metabolic syndrome. Opportunities
      for gender-specific prevention for men].
AB  - German men tend to be less health conscious and show less of an interest in
      preventative behaviours. However, urological symptoms can provide the grounds for
      a doctor's visit and conversation. Modifiable lifestyle factors such as obesity,
      lack of exercise and smoking play a role in the development, progression or
      remission not only of erectile dysfunction (ED), but also in cardiovascular
      disease and the metabolic syndrome. Moreover, age-related testosterone deficiency
      can negatively impact the overall health as well as the sexual function of men.
      Recommendations to alter behaviours in the context of ED management and, if
      necessary, testosterone replacement, provide the urologist with the opportunity
      for broad gender-specific prevention for his male patients.

PMID- 17431579
TI  - Variation in the peroxisome proliferator-activated receptor delta gene in
      relation to common metabolic traits in 7,495 middle-aged white people.
AB  - AIMS/HYPOTHESIS: Studies in animals reveal that peroxisome proliferator-activated
      receptor delta (PPARdelta) regulates glucose metabolism and insulin sensitivity
      in both the liver and skeletal muscles. Moreover, PPARdelta augments physical
      endurance and increases oxidative metabolism, thereby averting obesity. Thus, we
      hypothesised that common variation in the PPARD gene is associated with insulin
      resistance and metabolic traits. MATERIALS AND METHODS: We studied variation in
      the exonic region of PPARD. Based upon the results of variant detection and
      information derived from the HapMap data resource, we selected common variants
      and tag single-nucleotide polymorphisms for genotyping in 7,495 white subjects,
      including 1,416 patients with type 2 diabetes. RESULTS: Fourteen nucleotide
      variants were identified and a total of 12 variants capturing the common
      variation of PPARD were genotyped. In the population-based Inter99
      (ClinicalTrials.gov ID no: NCT00289237) sample we observed no robust association
      with homeostasis model assessment of insulin resistance (HOMA-IR), adiposity
      measures or fasting serum lipids. Similarly, no association with type 2 diabetes
      or the metabolic syndrome was found. CONCLUSIONS/INTERPRETATION: Based on
      thorough investigation, we conclude that common variation in PPARD does not
      significantly affect the risk of metabolic disease in the population studied.
      Given the confidence intervals that were found for effect size estimates, we can
      effectively rule out an increase in HOMA-IR of any tag SNP above 7% per allele,
      assuming an additive model. Likewise, we can exclude an odds ratio of type 2
      diabetes above 1.27 per allele.

PMID- 17431580
TI  - Modified end-stage renal disease risk score for Chinese type 2 diabetic patients-
      the Hong Kong Diabetes Registry.

PMID- 17431581
TI  - Use of recruitment maneuvers during mechanical ventilation in pediatric and
      neonatal intensive care units in the Netherlands.

PMID- 17431582
TI  - Serum lactate as a predictor of mortality in patients with infection.
AB  - OBJECTIVE: To determine the utility of an initial serum lactate measurement for
      identifying high risk of death in patients with infection. DESIGN AND SETTING:
      Post-hoc analysis of a prospectively compiled registry in an urban academic
      hospital. PARTICIPANTS: Patients with (a) a primary or secondary diagnosis of
      infection and (b) lactate measurement who were admitted over the 18 months
      following hospital-wide implementation of the Surviving Sepsis Campaign guideline
      for lactate measurement in patients with infection and possible severe sepsis.
      There were 1,177 unique patients, with an in-hospital mortality of 19%.
      MEASUREMENTS AND RESULTS: Outcome measures included acute-phase (<or=3 days)
      death and in-hospital death. We defined lactate ranges a priori (low, 0.0-2.0;
      intermediate, 2.1-3.9; high, 4.0 mmol/l or above)--and tested for linear
      associations with mortality by one-way analysis of variance. We determined
      sensitivity/specificity, odds ratios, and likelihood ratios for a lactate >or=4.0
      mmol/l and performed a Bayesian analysis to determine its impact on a full range
      (0.01-0.99) of hypothetical pretest probability estimates for death. In-hospital
      mortality was 15%, 25%, and 38% in low, intermediate, and high lactate groups,
      respectively. Acute-phase deaths and in-hospital deaths increased linearly with
      lactate. An initial lactate >or=4.0 mmol/l was associated with sixfold higher
      odds of acute-phase death; however, a lactate level less than 4 mmol/l had little
      impact on probability of death. CONCLUSIONS: When broadly implemented in routine
      practice, measurement of lactate in patients with infection and possible sepsis
      can affect assessment of mortality risk. Specifically, an initial lactate >or=4.0
      mmol/l substantially increases the probability of acute-phase death.

PMID- 17431583
TI  - Linezolid as rescue therapy for pneumococcal meningitis.

PMID- 17431584
TI  - Failure to achieve glycemic control despite intensive insulin therapy in a
      medical ICU: incidence and influence on ICU mortality.
AB  - OBJECTIVE: Intensive insulin therapy reduces mortality in subgroups of intensive
      care unit (ICU) patients, and awareness of the importance of blood glucose level
      (BGL) control has increased among ICU physicians and nurses. The impact of
      insulin treatment strategies on mortality may be influenced by their efficacy in
      achieving the target BGL range. We assessed the efficacy of an insulin treatment
      strategy in maintaining BGL within the target range, and we compared ICU
      mortality in patients who did and did not reach the BGL target. DESIGN:
      Prospective cohort study. SETTING: 12-bed medical ICU in a tertiary teaching
      hospital. PATIENTS AND PARTICIPANTS: Adults consecutively admitted over a 9-month
      period to an ICU where standard care included an insulin treatment strategy aimed
      at maintaining BGL<or=7 mmol/l. MEASUREMENTS AND MAIN RESULTS: 105 patients were
      included. Median SAPS II was 45 (31-54). Failure to control BGL (mean capillary
      BGL >7 mmol/l after initial hyperglycemia correction) occurred in 32 patients
      (31.1%) and was associated with a significant increase in ICU mortality (56.2 vs.
      23.3% in patients with successful BGL control). In the multivariate analysis,
      failure to control BGL independently predicted death in the ICU (OR 5.9, 2.1
      16.6, p<0.001). CONCLUSIONS: Failure to control BGL despite intensive insulin
      therapy was common and independently associated with ICU mortality. Failure to
      control BGL may considerably affect the overall impact of insulin treatment
      strategies on mortality.

PMID- 17431586
TI  - Treatment of patellar instability.

PMID- 17431587
TI  - Patellar tracking during total knee arthroplasty: an in vitro feasibility study.
AB  - Abnormal patellar tracking results in patello-femoral (PF) joint disorders and
      frequently in failure of total knee arthroplasty (TKA). It is fundamental to
      assess this tracking intra-operatively, i.e. since the implantation of the
      femoral and tibial components. The aim of this study was to assess the
      feasibility of three-dimensional anatomical-based patellar tracking intra
      operatively in standard TKA. A surgical navigation system was utilized to test
      the new technique in-vitro. An original tracking device and a reference frame
      were designed and an articular convention for the description of PF joint
      kinematics was adopted. Six fresh-frozen amputated legs were analyzed with the
      new technique. Landmark digitations were used to define anatomical reference
      frames for the femur, tibia, and patella. Five trials of passive flexion were
      performed with 100 N force on the quadriceps, before and after standard knee
      arthroplasty. Patellar flexion, tilt, rotation and shift were calculated in
      addition to standard tibio-femoral (TF) joint kinematics. An intra-specimen
      repeatable path of motion over repetitions and a coupled path of motion
      throughout the flexion-extension cycle were observed in all intact knees, both at
      the TF and PF joints. Replication of the original PF motion in the intact knee
      was not fully accomplished in the replaced knee. These results revealed the
      feasibility and the necessity of patellar tracking during TKA. By monitoring
      intra-operatively also the PF kinematics, the surgeon has a more complete
      prediction of the performance of the final implant and therefore a valuable
      support for the most critical surgical decisions.

PMID- 17431588
TI  - Glenohumeral motion: review of measurement techniques.
AB  - Measurement of upper limb motion is problematic, not least because of the large
      range of path dependent description of motion of the joints, and the multiple non
      cyclical unstandardised motion tasks measured. Furthermore, appreciation of
      shoulder motion specifically is obscured by overlying soft tissue. In order to
      satisfy the complexity of a clinically useful model of the movement of the joint,
      input data must be acquired from a set of pre-determined movements using a non
      invasive technique with a high level of accuracy. Descriptive and predictive
      modeling of the glenohumeral joint requires input of high-fidelity data into a 6
      degree of freedom representation, without which, the application of the tool is
      of limited clinical significance to the advancement of both operative and non
      operative management of shoulder pathology. Electromagnetic, linkage and
      radiographic techniques have previously been used, however, an optimal solution
      is yet to be described.

PMID- 17431589
TI  - Induction of CYP1A1 and CYP2E1 in rat liver by histamine: binding and kinetic
      studies.
AB  - Histamine (HA) may bind to cytochrome P450 (CYP450) in rat liver microsomes. The
      CYP450-HA complex seems to regulate some cellular processes such as
      proliferation. In the present work, it is shown that HA increases the activity
      and protein level of CYP1A1 and CYP2E1, in vivo. CYP1A1 is associated with
      polycyclic aromatic hydrocarbon-mediated carcinogenesis and CYP2E1 with liver
      damage by oxidative stress. Studies of enzyme kinetics and binding with rat liver
      microsomes and supersomes were carried out to determine whether HA is a substrate
      of CYP1A1 and/or CYP2E1. The lack of NADPH oxidation in the presence of HA showed
      that it is not a substrate for CYP1A1. Activity measurements using the O
      dealkylation of ethoxyresorufin indicated that HA is a mixed-type inhibitor of
      CYP1A1 in both microsomes and supersomes. On the other hand, HA induced a
      significant NADPH oxidation catalyzed by CYP2E1 supersomes, strongly suggesting
      that HA is a substrate for this isoform. Furthermore, HA is consumed in the
      presence of CYP2E1-induced microsomes and supersomes, as determined by o
      phtalaldehyde complexes with HA by HPLC. The present findings may contribute to
      understand better the physiological function of CYP450 in relation with
      inflammation and other physiological processes in which HA may have a relevant
      role.

PMID- 17431590
TI  - VEGF isoforms and receptors expression throughout acute acetaminophen-induced
      liver injury and regeneration.
AB  - Acetaminophen (APAP) is a widely-used analgesic and a known hepatotoxic agent.
      Vascular endothelial growth factor (VEGF) is a growth factor with multiple
      functional roles. VEGF plays an important role in angiogenesis and hepatic
      regeneration. The aim of this study was to determine the expression of VEGF
      isoforms and its receptors throughout liver regeneration after the administration
      of a toxic dose of APAP in rats. Ten groups of adult male rats received a dose of
      3.5 g/kg b.w. of APAP per os. The rats were killed post administration at 0-288
      h. Blood and liver tissue were extracted. Determination of serum transaminases
      and alkaline phosphatase activities was performed. Liver injury and regeneration
      were assessed with hematoxylin-eosin specimens, morphometric analysis, hepatic
      thymidine kinase assay and Ki-67 expression. Reverse transcription-polymerase
      chain reaction and immunohistochemical methods were used for assessment of VEGF
      isoforms and receptors differential expression. High activities of aspartate
      aminotransferase were observed at 24 and 36 h with another peak of activity at
      192 h post administration. Alanine aminotransferase was highest at 36 h. Alkaline
      phosphatase was increased post 24 h being higher at 72,192 and 240 h.
      Centrilobular necrosis was observed at 48-72 h and thorough restoration of the
      liver microarchitecture was observed at 288 h. Liver regeneration lasted from 24
      192 h according to the results from thymidine kinase activity and Ki-67
      expression. VEGF and VEGF receptor-2 m-RNA levels presented with a three-peak
      pattern of expression at 12-24, 72-96 and 192-240 h post administration.
      Significant difference was noted between periportal and centrilobular
      immunohistochemical expression. VEGF proves to play a critical role during APAP
      induced liver regeneration as it presents with three points of higher expression.
      The first two time points are associated with the initial inflammatory reaction
      to the noxious stimulus and the hepatocyte regenerative process where as the
      third one is indicative of the potential involvement of VEGF in processes of
      remodeling.

PMID- 17431592
TI  - Determination of total trans fats and oils by infrared spectroscopy for
      regulatory compliance.
AB  - The mandatory requirement in many countries to declare the amount of trans fat
      present in food products and dietary supplements has led to a need for sensitive
      and accurate methodologies for the rapid quantitation of total trans fats and
      oils. Capillary gas chromatography (GC) and infrared spectroscopy (IR) are the
      two methods most commonly used to identify and quantify trans fatty acids for
      food labeling purposes (see the article by Delmonte and Rader in this ABC issue
      for a detailed presentation of GC methodology). The present article provides a
      comprehensive review of the IR technique and the current attenuated total
      reflection (ATR) Fourier-transform (FT) IR methodologies for the rapid
      determination of total trans fats and oils. This review also addresses potential
      sources of interferences and inaccuracies in FTIR determinations, particularly
      those done at low trans levels. Recent observations have shown that the presence
      of saturated fats caused interferences in the FTIR spectra observed for trans
      triacylglycerols. The recognition and resolution of previously unresolved
      quantitative issues improved the accuracy and sensitivity of the FTIR
      methodology. Once validated, it is anticipated that the new negative second
      derivative ATR-FTIR procedure will make IR spectroscopy more suitable than ever,
      and a rapid alternative and/or complementary method to GC, for the rapid
      determination of total trans fats for regulatory compliance. Figure Infrared
      light bouncing inside an internal reflection crystal.

PMID- 17431593
TI  - Origin and fate of platinum group elements in the environment.

PMID- 17431591
TI  - Effects of the noradrenergic agonist clonidine on temporal and spatial attention.
AB  - RATIONALE: Recent theories posit an important role for the noradrenergic system
      in attentional selection in the temporal domain. In contrast, the spatially
      diffuse topographical projections of the noradrenergic system are inconsistent
      with a direct role in spatial selection. OBJECTIVES: To test the hypotheses that
      pharmacological attenuation of central noradrenergic activity should (1) impair
      performance on the attentional blink task, a task requiring the selection of
      targets in a rapid serial visual stream of stimuli; and (2) leave intact the
      efficiency of the search for a target in a two-dimensional visuospatial stimulus
      array. MATERIALS AND METHODS: Thirty-two healthy adult human subjects performed
      an attentional blink task and a visual search task in a double-blind, placebo
      controlled, between-subject study investigating the effects of the alpha2
      adrenoceptor agonist clonidine (150 microg, oral dose). RESULTS: No differential
      effects of clonidine vs placebo were found on the attentional blink performance.
      Clonidine slowed overall reaction times in the visual search task but did not
      impair the efficiency of the visual search. CONCLUSIONS: The attentional blink
      results are inconsistent with recent theories about the role of the noradrenergic
      system in temporal filtering and in mediating the attentional blink. This
      discrepancy between theory and data is discussed in detail. The visual search
      results, in combination with previous findings, suggest that the noradrenergic
      system is not directly involved in spatial attention processes but instead can
      modulate these processes in an indirect fashion.

PMID- 17431594
TI  - Recent progress in analytical instrumentation for glycemic control in diabetic
      and critically ill patients.
AB  - Implementing strict glycemic control can reduce the risk of serious complications
      in both diabetic and critically ill patients. For this reason, many different
      analytical, mainly electrochemical and optical sensor approaches for glucose
      measurements have been developed. Self-monitoring of blood glucose (SMBG) has
      been recognised as being an indispensable tool for intensive diabetes therapy.
      Recent progress in analytical instrumentation, allowing submicroliter samples of
      blood, alternative site testing, reduced test time, autocalibration, and improved
      precision, is comprehensively described in this review. Continuous blood glucose
      monitoring techniques and insulin infusion strategies, developmental steps
      towards the realization of the dream of an artificial pancreas under closed loop
      control, are presented. Progress in glucose sensing and glycemic control for both
      patient groups is discussed by assessing recent published literature (up to
      2006). The state-of-the-art and trends in analytical techniques (either episodic,
      intermittent or continuous, minimal-invasive, or noninvasive) detailed in this
      review will provide researchers, health professionals and the diabetic community
      with a comprehensive overview of the potential of next-generation instrumentation
      suited to either short- and long-term implantation or ex vivo measurement in
      combination with appropriate body interfaces such as microdialysis catheters.

PMID- 17431595
TI  - A new molecularly imprinted polymer for the on-column solid-phase extraction of
      diethylstilbestrol from aqueous samples.
AB  - The estrogenic compound diethylstilbestrol (DES) is widely studied because of its
      potential endocrine disruption effects. The prohibition of the use of
      diethylstilbestrol as a growth promoter has not been enough to ensure the total
      disappearance of this compound from environmental matrices. Due to the low levels
      of DES present in the environment, preconcentration and clean up methods are
      necessary for its analysis. This paper describes the synthesis and use of a
      molecularly imprinted polymer (MIP) as sorbent for on-column solid-phase
      extraction of DES from aqueous samples. The selectivity of the DES-MIP was
      evaluated towards several selected estrogens such as hexestrol (HEX), estrone
      (E1), estriol (E3), estradiol (E2) and ethynylestradiol (EE2). HPLC-DAD was used
      to quantify all analytes at 230-nm wavelength. The method has been successfully
      applied to the analysis of DES in spiked river and tap water samples, with
      recoveries of 72% and 83% respectively.

PMID- 17431596
TI  - Ultrasound-assisted vapor generation of mercury.
AB  - Cold vapor generation arising from reduction of both Hg(2+) and CH(3)Hg(+) occurs
      using ultrasonic (US) fields of sufficient density to achieve both localized
      heating as well as radical-based attack in solutions of formic and acetic acids
      and tetramethylammonium hydroxide (TMAH). A batch sonoreactor utilizing an
      ultrasonic probe as an energy source and a flow through system based on a US bath
      were optimized for this purpose. Reduction of CH(3)Hg(+) to Hg(0) occurs only at
      relatively high US field density (>10 W cm(-3) of sample solution) and is thus
      not observed when a conventional US bath is used for cold vapor generation.
      Speciation of mercury is thus possible by altering the power density during the
      measurement process. Thermal reduction of Hg(2+) is efficient in formic acid and
      TMAH at 70 degrees C and occurs in the absence of the US field. Room temperature
      studies with the batch sonoreactor reveal a slow reduction process, producing
      temporally broad signals having an efficiency of approximately 68% of that
      arising from use of a conventional SnCl(2) reduction system. Molecular species of
      mercury are generated at high concentrations of formic and acetic acid. Factors
      affecting the generation of Hg(0) were optimized and the batch sonoreactor used
      for the determination of total mercury in SLRS-4 river water reference material.

PMID- 17431597
TI  - Stabilometric signal analysis in tests with sound stimuli.
AB  - Posture control is mediated by the integration between the environment
      information (coming from the visual, somatosensory and vestibular systems) and
      the efferent organs (motoneurons and muscles). The influence of the first systems
      on body sway signals is already documented in the literature. Few studies are
      focused in the relationship between stabilometric signals (objective measure of
      stability) and vestibular stimulation, due to the difficulty in achieving a
      specific and independent stimulation of this system. The present study sought to
      examine this aspect, proposing high intensity sounds as a way to perturb the
      vestibular system, based on vestibular evoked myogenic potentials theory. Sixty
      six volunteers were submitted to a variety of sound stimulation conditions (pure
      tones, clicks and bursts) while they stayed in upright position on a force
      platform. The variables recorded were mean position, mean standard deviation,
      mean velocity, mean displacement, mean frequency (all of them in lateral and
      anterior-posterior directions) and sway area. Values obtained in each variable
      were treated by an analysis of variance (ANOVA). Results confirmed the influence
      of visual system in the mean velocity of center of pressure. No statistic
      difference was found when conditions with and without sound stimulation were
      compared by ANOVA at the same visual condition with any type of sound. However,
      visual analysis of the plot of mean lateral displacement and anterior-posterior
      standard deviation shows some consistent patterns of change during the recovery
      phase after stimulation, confirmed, sometimes, by Wilcoxon test. This result
      shows that balance is not always influenced by the types of sound stimulation
      used in this work. It encourages future experiments setting louder intensities,
      as well as other sources of stimulus that could affect vestibular receptors
      (direct or indirectly), to search for specific modifications in the stabilometric
      signal.

PMID- 17431598
TI  - Temporal recalibration during asynchronous audiovisual speech perception.
AB  - We investigated the consequences of monitoring an asynchronous audiovisual speech
      stream on the temporal perception of simultaneously presented vowel-consonant
      vowel (VCV) audiovisual speech video clips. Participants made temporal order
      judgments (TOJs) regarding whether the speech-sound or the visual-speech gesture
      occurred first, for video clips presented at various different stimulus onset
      asynchronies. Throughout the experiment, half of the participants also monitored
      a continuous stream of words presented audiovisually, superimposed over the VCV
      video clips. The continuous (adapting) speech stream could either be presented in
      synchrony, or else with the auditory stream lagging by 300 ms. A significant
      shift (13 ms in the direction of the adapting stimulus in the point of subjective
      simultaneity) was observed in the TOJ task when participants monitored the
      asynchronous speech stream. This result suggests that the consequences of
      adapting to asynchronous speech extends beyond the case of simple audiovisual
      stimuli (as has recently been demonstrated by Navarra et al. in Cogn Brain Res
      25:499-507, 2005) and can even affect the perception of more complex speech
      stimuli.

PMID- 17431599
TI  - Coordination between postural and movement controls: effect of changes in body
      mass distribution on postural and focal component characteristics.
AB  - Whole-body reaching movements are accomplished through a combination of
      anticipatory postural adjustments (APAs) and focal movements. Two different modes
      of central organization is usually proposed for this coordination: first, a
      single-process control, where the APAs and the focal movements would share a
      common command; second, where the APAs and the focal movements would be
      independently controlled through parallel commands (dual-process control). Here,
      we investigated which one of these modes of control could better explain the
      coordination between the trunk and the upper limb for standing subjects reaching
      for a target located beyond arm's length. This was done evaluating the effect of
      changing the APAs settings on the arm movement. The APAs modification was
      achieved by shifting the subject's centre of mass prior to the focal movement
      onset; this was done by adding an asymmetric load on either side of the head (a
      control condition with the load fixed centrally at the top of the head was also
      performed). As it changed the body mass distribution, the muscular torques and
      the orientation of the head inertia tensor, it is assumed that the addition of
      the asymmetric load led to a change in the APAs. Analyses indeed showed that both
      the initial head and trunk displacement towards the supporting side (during the
      unloading of the moving leg) were smaller when the load was fixed on the side of
      the supporting leg than when it was fixed on the side of the moving leg. However,
      changing the initial conditions, and therefore the APAs settings, had no
      significant effect on the path and kinematics of the focal hand movement.
      Therefore, subjects cancelled out the effect of the trunk motion on the hand-in
      space motion through compensatory arm movements. These results support the dual
      process control hypothesis for the postural and the focal components.

PMID- 17431600
TI  - Adaptation of a bimodal integration stage: visual input needed during neck muscle
      vibration to elicit a motion aftereffect.
AB  - Vibratory stimulation of the neck muscles can elicit illusory drift of a visual
      target; after vibration stops, motion in the opposite direction is perceived.
      This motion aftereffect (MAE) could be due to adaptation of proprioceptive
      mechanisms that encode head orientation, or at a stage where visual and
      proprioceptive information are combined. To distinguish between these two
      possibilities, we applied vibratory stimulation to dorsolateral neck muscles for
      15-s periods alternating with 15-s periods without vibration. Twenty-six
      observers used a hand-held tracker to indicate perceived motion of a stationary
      light-emitting diode (LED) in an otherwise dark room. In the critical condition,
      observers were in complete darkness during vibration, and the LED was only turned
      on in post-vibration periods. If adaptation was purely proprioceptive, a visual
      MAE should have occurred in this condition, but it did not. In a follow-up
      experiment (N = 9), the LED was presented intermittently to determine if there
      was a position aftereffect that might have been inhibited by processes signalling
      an absence of motion. No aftereffect occurred under these conditions either. In
      both experiments, a visual stimulus had to be present during the adaptation
      period in order to elicit an aftereffect. Results from our previous study ruled
      out an explanation based on suppression of eye movements. Thus, the most likely
      site responsible for the visual aftereffect lies with bimodal mechanisms
      combining proprioceptive and visual information. We conclude that the bimodal
      mechanisms adapted more quickly than the proprioceptive mechanisms from which
      they received input.

PMID- 17431601
TI  - Spectral receptive field properties of neurons in the feline superior colliculus.
AB  - The spatio-temporal frequency response profiles of 73 neurons located in the
      superficial, retino-recipient layers of the feline superior colliculus (SC) were
      investigated. The majority of the SC cells responded optimally to very low
      spatial frequencies with a mean of 0.1 cycles/degree (c/deg). The spatial
      resolution was also low with a mean of 0.31 c/deg. The spatial frequency tuning
      functions were either low-pass or band-pass with a mean spatial frequency
      bandwidth of 1.84 octaves. The cells responded optimally to a range of temporal
      frequencies between 0.74 cycles/s (c/s) and 26.41 c/s with a mean of 6.84 c/s.
      The majority (68%) of the SC cells showed band-pass temporal frequency tuning
      with a mean temporal frequency bandwidth of 2.4 octaves, while smaller
      proportions of the SC units displayed high-pass (19%), low-pass (8%) or broad
      band (5%) temporal tuning. Most of the SC units exhibited simple spectral tuning
      with a single maximum in the spatio-temporal frequency domain, while some neurons
      were tuned for spatial or temporal frequencies or speed tuned. Further, we found
      cells excited by gratings moving at high temporal and low spatial frequencies and
      cells whose activity was suppressed by high velocity movement. The spatio
      temporal filter properties of the SC neurons show close similarities to those of
      their retinal Y and W inputs as well as those of their inputs from the cortical
      visual motion detector areas, suggesting their common role in motion analysis and
      related behavioral actions.

PMID- 17431602
TI  - Predictive value of changes in electroencephalogram and excitatory postsynaptic
      field potential for CA1 damage after global ischaemia in rats.
AB  - Recordings of the electroencephalogram (EEG) are regularly used to asses the
      severity of transient global ischaemia in rats. Here, we investigated whether the
      EEG obtained from electrodes placed in the hippocampus does indeed give valuable
      information about the consequences of an ischaemic event. Furthermore, we
      evaluated how evoked synaptic responses from the same electrodes placed in the
      hippocampal CA1 area changed with time and in relation to damage. We performed
      transient two vessel-occlusion with hypobaric hypotension in rats to induce
      selective, delayed neuronal death in CA1. Beforehand, the animals had been
      chronically implanted with electrodes. Stimulating electrodes had been placed
      into the Schaffer collaterals and recording electrodes into the CA1 area. EEG was
      recorded from shortly before ischaemia until up to 40 min post-ischaemia. Field
      excitatory post-synaptic potentials (fEPSP) were recorded before ischaemia or
      sham-operation and 2 and 7 days afterwards. We found a significant negative
      correlation between the duration of the EEG amplitude decrease (flattening) and
      the number of surviving neurons in CA1, which were quantified by histology after
      7 days post-ischaemia. However, substantial neuronal damage was only seen when
      the time of flattening was more than 12 min and outlasted the time of ischaemia.
      The impairment of synaptic function, measured as the decrease of fEPSP slope 2
      days post-ischaemia correlated with the later maturated structural damage in CA1.
      The fEPSP remained decreased until day 7 post-ischaemia. Animals with no damage
      (sham condition) showed a transient decrease of the fEPSP slope. In conclusion,
      our data show that the duration of EEG-flattening predicts the extent of neuronal
      damage. However, EEG-flattening just during the period of clamping both common
      carotid arteries--albeit an essential precondition for substantial CA1 cell loss
      to occur--is not sufficient to predict damage. The degree of impairment of evoked
      synaptic function of CA1 neurons (fEPSP) 2 days after ischaemia predicts the
      final extent of damage with significant probability.

PMID- 17431603
TI  - Tadalafil population pharmacokinetics in patients with erectile dysfunction.
AB  - OBJECTIVE: The purpose of this study was to characterize pharmacokinetics of
      tadalafil (Cialis) and potential sources of variability in patients with erectile
      dysfunction (ED). METHODS: Population models were developed to describe tadalafil
      pharmacokinetics in 227 patients with mild to severe ED in a phase III trial.
      Parallel groups of patients received 2, 5, or 10 mg tadalafil or placebo orally,
      as needed, for 12 weeks. RESULTS: Tadalafil pharmacokinetics in patients with ED
      were linear with respect to dose and duration of treatment, and a one-compartment
      model adequately described the data. The absorption rate was rapid (1.86 h(-1)),
      and the typical population estimates of the apparent oral clearance (CL/F) and
      apparent volume of distribution were 1.6 l/h and 63.8 l, respectively.
      Disposition parameters showed a moderate degree of interindividual variability
      (39-45%). The value of CL/F decreased slightly with increasing serum gamma
      glutamyl transferase (GGT) concentration, the only statistically significant
      covariate detected. Systemic exposure to tadalafil was not influenced by age,
      weight, smoking status, alcohol consumption, liver enzyme status, ED severity,
      cardiovascular condition, or diabetes mellitus. CONCLUSION: Pharmacokinetics in
      the efficacy/safety trial population are essentially similar to pharmacokinetics
      in healthy subjects, and no patient-specific factor warranting clinical
      consideration of dose regimen adjustment was identified in these analyses.

PMID- 17431604
TI  - Intestinal and renal handling of oxalate loads in normal individuals and stone
      formers.
AB  - The renal handling and intestinal absorption of dietary oxalate are believed to
      be risk factors for calcium oxalate stone formation. In this study, we have
      examined the time and dose effects of soluble oxalate loads on the intestinal
      absorption and renal handling of oxalate in six stone formers (SF) and six normal
      individuals (N) who consumed diets controlled in oxalate and other nutrients.
      Urinary and plasma oxalate changes were monitored over 24 h after ingestion of 0,
      2, 4, and 8 mmole oxalate loads, containing a mixture of (12)C- and (13)C(2)
      oxalate. There were significant time and dose dependent changes in urinary
      oxalate excretion and secretion after these loads. However, there were no
      significant differences between SF and N in both the intestinal absorption and
      the renal handling of oxalate loads, as measured by the urinary excretion of
      oxalate (P = 0.96) and the ratio of oxalate to creatinine clearance (P = 0.34).
      (13)C(2)-oxalate absorption studies showed three of the subjects, two SF and one
      N, had enhanced absorption with the 8 mmole load. A clear difference in
      absorption was demonstrated in these individuals during the 8-24 h interval,
      suggesting that in these individuals there was greater oxalate absorption in the
      large intestine as compared to the other subjects. This enhanced absorption of
      oxalate warrants further characterization.

PMID- 17431605
TI  - The path less travelled--a road to success.

PMID- 17431607
TI  - Continuing problems with classifications of vascular malformations.

PMID- 17431606
TI  - Pediatric DXA: clinical applications.
AB  - Normal bone mineral accrual requires adequate dietary intake of calcium, vitamin
      D and other nutrients; hepatic and renal activation of vitamin D; normal hormone
      levels (thyroid, parathyroid, reproductive and growth hormones); and
      neuromuscular functioning with sufficient stress upon the skeleton to induce bone
      deposition. The presence of genetic or acquired diseases and the therapies that
      are used to treat them can also impact bone health. Since the introduction of
      clinical DXA in pediatrics in the early 1990s, there has been considerable
      investigation into the causes of low bone mineral density (BMD) in children.
      Pediatricians have also become aware of the role adequate bone mass accrual in
      childhood has in preventing osteoporotic fractures in late adulthood.
      Additionally, the availability of medications to improve BMD has increased with
      the development of bisphosphonates. These factors have led to the increased
      utilization of DXA in pediatrics. This review summarizes much of the previous
      research regarding BMD in children and is meant to assist radiologists and
      clinicians with DXA utilization and interpretation.

PMID- 17431608
TI  - A statistical light scattering approach to separating fast and slow dynamics:
      application to a model system.
AB  - Light scattering is a powerful technique to study the structural and dynamical
      properties of biomolecular systems or other soft materials such as polymeric
      solutions and blends or gels. An important application of this technique is the
      study of the kinetics of formation of supramolecular structures. However, in such
      cases, the system under study is rapidly changing, and consequently the
      integration time for each measurement is limited. In order to overcome this
      difficulty, a statistical approach has been developed based on the analysis of
      the scattered light intensity distribution (Manno et al. 2006, 2004). Indeed the
      intensity distribution depends upon the ratio between the integration time of
      each measurement and the coherence time of scattered radiation. This method has
      been applied to protein aggregation (Manno et al. 2006) and to sol-gel transition
      (Manno et al. 2004), to obtain information on the heterogeneity of morphological
      and dynamical features during such processes. In the present work, we accurately
      test the validity of this approach by analyzing the statistical properties of the
      light scattered by a model system: a solution of polystyrene spherical
      macromolecules of different sizes. Each molecular size is related to a given
      diffusion coefficient and to a given coherence time of the scattered intensity.
      The effect of changing the experimental integration time is systematically
      investigated. A mixture of particles of two different sizes is also analyzed to
      test the validity and robustness of the model based on the convolution of a
      gaussian with an exponential distribution.

PMID- 17431609
TI  - Atomic force microscopy images suggest aggregation mechanism in cerato-platanin.
AB  - Cerato-platanin (CP), the first member of the "cerato-platanin family", is a
      moderately hydrophobic protein produced by Ceratocystis fimbriata, the causal
      agent of a severe plant disease called "canker stain". The protein is localized
      in the cell wall of the fungus and it seems to be involved in the host-plane
      interaction and induces both cell necrosis and phytoalexin synthesis (one of the
      first plant defence-related events). Recently, it has been determined that CP,
      like other fungal surface protein, is able to self assemble in vitro. In this
      paper we characterize the aggregates of CP by Atomic Force Microscopy (AFM)
      images. We observe that CP tends to form early annular-shaped oligomers that seem
      to constitute the fundamental bricks of a hierarchical aggregation process,
      eventually resulting in large macrofibrillar assemblies. A simple model, based on
      the hypothesis that the aggregation is energetically favourable when the exposed
      surface is reduced, is compatible with the measured aggregates' shape and size.
      The proposed model can help to understand the mechanism by which CP and many
      other fungal surface proteins exert their effects.

PMID- 17431610
TI  - Comparison of volatile sulphur compound production by cheese-ripening yeasts from
      methionine and methionine-cysteine mixtures.
AB  - Production of volatile sulphur compounds (VSC) was assessed in culture media
      supplemented with L-methionine or L-methionine/L-cysteine mixtures, using five
      cheese-ripening yeasts: Debaryomyces hansenii DH47(8), Kluyveromyces lactis
      KL640, Geotrichum candidum GC77, Yarrowia lipolytica YL200 and Saccharomyces
      cerevisiae SC45(3). All five yeasts produced VSC with L-methionine or L
      methionine/L-cysteine, but different VSC profiles were found. GC77 and YL200
      produced dimethyldisulphide and trace levels of dimethyltrisulphide while
      DH47(8), KL640 and SC45(3) produced mainly methionol and low levels of methional.
      S-methylthioacetate was produced by all the yeasts but at different
      concentrations. DH47(8), KL640 and SC45(3) also produced other minor VSC
      including 3-methylthiopropyl acetate, ethyl-3-methylthiopropanoate, a
      thiophenone, and an oxathiane. However, VSC production diminished in a strain
      dependent behaviour when L-cysteine was supplemented, even at a low concentration
      (0.2 g l(-1)). This effect was due mainly to a significant decrease in L
      methionine consumption in all the yeasts except YL200. Hydrogen sulphide produced
      by L-cysteine catabolism did not seem to contribute to VSC generation at the acid
      pH of yeast cultures. The significance of such results in the cheese-ripening
      context is discussed.

PMID- 17431611
TI  - Application of DNA methyltransferases in targeted DNA methylation.
AB  - DNA methylation is an essential epigenetic modification. In bacteria, it is
      involved in gene regulation, DNA repair, and control of cell cycle. In
      eukaryotes, it acts in concert with other epigenetic modifications to regulate
      gene expression and chromatin structure. In addition to these biological roles,
      DNA methyltransferases have several interesting applications in biotechnology,
      which are the main focus of this review, namely, (1) in vivo footprinting: as
      several bacterial DNA methyltransferases cannot methylate DNA bound to histone
      proteins, the pattern of DNA methylation after expression of DNA
      methyltransferases in the cell allows determining nucleosome positioning; (2)
      mapping the binding specificity of DNA binding proteins: after fusion of a DNA
      methyltransferase to a DNA-binding protein and expression of the fusion protein
      in a cell, the DNA methylation pattern reflects the DNA-binding specificity of
      the DNA-binding protein; and (3) targeted gene silencing: after fusion of a DNA
      methyltransferase to a suitable DNA-binding domain, DNA methylation can be
      directed to promoter regions of target genes. Thereby, gene expression can be
      switched off specifically, efficiently, and stably, which has a number of
      potential medical applications.

PMID- 17431612
TI  - Positron detection for the intraoperative localisation of cancer deposits.
AB  - PURPOSE: The study investigated the feasibility of a positron-sensitive hand-held
      detector system for the intraoperative localisation of tumour deposits resulting
      from intravenous [(18)F]FDG administration. METHODS: A total of 17 patients (12
      receiving preoperative [(18)F]FDG PET imaging) with various histologically proven
      malignancies were included. Radioactivity from tumours and surrounding normal
      tissue was measured on average 3 h after administration of 36-110 MBq [(18)F]FDG
      and the tumour-to-background (T/B) ratio was calculated. In addition, phantom
      studies were performed to evaluate the spatial resolution and sensitivity of the
      probe. RESULTS: All known targeted tumour sites were identified by the positron
      probe. T/B ratios were generally high, with a mean T/B ratio of 6.6, allowing
      easy identification of most tumour sites. In one case of a hepatic metastasis,
      the T/B ratio of 1.34 was below expectations, since the preoperative [(18)F]FDG
      PET scan was positive. The probe was instrumental in the localisation of three
      additional tumour lesions (two lymph nodes, one anastomotic ring) that were not
      immediately apparent at surgery. Phantom studies revealed that [(18)F]FDG
      containing gel (simulating tumour tissue), having 10 times more [(18)F]FDG than
      surrounding "normal" background gel, was clearly detectable in quantities as low
      as 15 mg. As measured in two cases, the absorbed radiation doses ranged from 2.5
      to 8.6 microSv/h for the surgical team to 0.8 microSv/h for the aesthetician.
      CONCLUSION: [(18)F]FDG-accumulating tumour tissues can be localised with positron
      probes intraoperatively with a low radiation burden to the patient and medical
      personnel. The methodology holds promise for further clinical testing.

PMID- 17431613
TI  - Activity of nuclear cardiology in the Czech Republic between 2000 and 2005.

PMID- 17431614
TI  - Radioguided localisation (ROLL) of non-palpable breast lesions and simultaneous
      sentinel lymph node biopsy (SNOLL): the experience of the European Institute of
      Oncology.

PMID- 17431615
TI  - Predictive value of brain perfusion SPECT for ketamine response in hyperalgesic
      fibromyalgia.
AB  - PURPOSE: Ketamine has been used successfully in various proportions of
      fibromyalgia (FM) patients. However, the response to this specific treatment
      remains largely unpredictable. We evaluated brain SPECT perfusion before
      treatment with ketamine, using voxel-based analysis. The objective was to
      determine the predictive value of brain SPECT for ketamine response. METHODS:
      Seventeen women with FM (48 +/- 11 years; ACR criteria) were enrolled in the
      study. Brain SPECT was performed before any change was made in therapy in the
      pain care unit. We considered that a patient was a good responder to ketamine if
      the VAS score for pain decreased by at least 50% after treatment. A voxel-by
      voxel group analysis was performed using SPM2, in comparison to a group of ten
      healthy women matched for age. RESULTS: The VAS score for pain was 81.8 +/- 4.2
      before ketamine and 31.8 +/- 27.1 after ketamine. Eleven patients were considered
      "good responders" to ketamine. Responder and non-responder subgroups were similar
      in terms of pain intensity before ketamine. In comparison to responding patients
      and healthy subjects, non-responding patients exhibited a significant reduction
      in bilateral perfusion of the medial frontal gyrus. This cluster of hypoperfusion
      was highly predictive of non-response to ketamine (positive predictive value
      100%, negative predictive value 91%). CONCLUSION: Brain perfusion SPECT may
      predict response to ketamine in hyperalgesic FM patients.

PMID- 17431616
TI  - A gradient-based method for segmenting FDG-PET images: methodology and
      validation.
AB  - PURPOSE: A new gradient-based method for segmenting FDG-PET images is described
      and validated. METHODS: The proposed method relies on the watershed transform and
      hierarchical cluster analysis. To allow a better estimation of the gradient
      intensity, iteratively reconstructed images were first denoised and deblurred
      with an edge-preserving filter and a constrained iterative deconvolution
      algorithm. Validation was first performed on computer-generated 3D phantoms
      containing spheres, then on a real cylindrical Lucite phantom containing spheres
      of different volumes ranging from 2.1 to 92.9 ml. Moreover, laryngeal tumours
      from seven patients were segmented on PET images acquired before laryngectomy by
      the gradient-based method and the thresholding method based on the source-to
      background ratio developed by Daisne (Radiother Oncol 2003;69:247-50). For the
      spheres, the calculated volumes and radii were compared with the known values;
      for laryngeal tumours, the volumes were compared with the macroscopic specimens.
      Volume mismatches were also analysed. RESULTS: On computer-generated phantoms,
      the deconvolution algorithm decreased the mis-estimate of volumes and radii. For
      the Lucite phantom, the gradient-based method led to a slight underestimation of
      sphere volumes (by 10-20%), corresponding to negligible radius differences (0.5
      1.1 mm); for laryngeal tumours, the segmented volumes by the gradient-based
      method agreed with those delineated on the macroscopic specimens, whereas the
      threshold-based method overestimated the true volume by 68% (p=0.014). Lastly,
      macroscopic laryngeal specimens were totally encompassed by neither the threshold
      based nor the gradient-based volumes. CONCLUSION: The gradient-based segmentation
      method applied on denoised and deblurred images proved to be more accurate than
      the source-to-background ratio method.

PMID- 17431617
TI  - Treatment of hepatocellular carcinoma in a mouse xenograft model with an
      immunotoxin which is engineered to eliminate vascular leak syndrome.
AB  - Vascular leak syndrome (VLS) is the major dose-limiting toxicity of immunotoxin
      and interleukin-2 therapy. It has been evidenced that VLS-inducing molecules
      share a three-amino acid consensus motif, (x)D(y), which may be responsible for
      initiating VLS. Here we have constructed a recombinant immunotoxin (SMFv
      PE38KDEL) by genetically fusing PE38KDEL to a single-chain antibody derived from
      SM5-1 monoclonal antibody, which has a high specificity for melanoma,
      hepatocellular carcinoma and breast cancer. In order to eliminate VLS induced by
      this PE38KDEL-based immunotoxin, a panel of mutants were generated by changing
      amino acid residues adjacent to its three (x)D(y) motifs in the three-dimensional
      structure. One of the SMFv-PE38KDEL mutants, denoted as mut1, displayed a similar
      protein synthesis inhibitory in a reticulocyte lysate translation assay compared
      to the wild-type SMFv-PE38KDEL (wt). The in vitro cytotoxicity assay indicated
      that mut1 specifically killed SM5-1 binding protein-positive tumor cells,
      although its cytotoxicity was slightly less than wt. In contrast, mut1 was shown
      to be much weaker in inducing VLS in mice than wt. The LD(50) values of wt and
      mut1 in mice were investigated with the result that the LD(50) of mut1 was about
      tenfold higher than that of wt. The in vivo antitumor activity of wt and mut1
      were also compared in tumor-bearing nude mice. Both wt and mut1 were effective in
      inhibiting the tumor growth but mut1 showed improved therapeutic efficacy. These
      studies suggest mut1 may be a novel PE-based immunotoxin with much less toxicity
      for clinical use.

PMID- 17431618
TI  - Interleukin-4 impairs granzyme-mediated cytotoxicity of Simian virus 40 large
      tumor antigen-specific CTL in BALB/c mice.
AB  - In this report we analyzed the impact of interleukin-4 (IL-4) on tumor-associated
      simian virus 40 (SV40) large T-antigen (TAg)-specific CD8+ cytotoxic T cells
      during rejection of syngeneic SV40 transformed mKSA tumor cells in BALB/c mice.
      Strikingly, challenge of naive mice with low doses of mKSA tumor cells revealed a
      CD8+ T cell-dependent prolonged survival time of naive IL-4-/- mice. In mice
      immunized with SV40 TAg we observed in IL-4-/- mice, or in wild type mice treated
      with neutralizing anti-IL-4 monoclonal antibody, a strongly enhanced TAg-specific
      cytotoxicity of tumor associated CD8+ T cells. The enhanced cytotoxicity in IL-4
      /- mice was accompanied by a significant increase in the fraction of CD8+ tumor
      associated T-cells expressing the cytotoxic effector molecules granzyme A and B
      and in granzyme B-specific enzymatic activity. The data suggest that endogenous
      IL-4 can suppress the generation of CD8+ CTL expressing cytotoxic effector
      molecules especially when the antigen induces only a very weak CTL response.

PMID- 17431619
TI  - The effect of graft choice on functional outcome in anterior cruciate ligament
      reconstruction.
AB  - A prospective, randomised, 5-year follow-up study was designed to compare the
      functional results between patellar tendon and hamstring tendon autografts after
      anterior cruciate ligament reconstruction. Primary reconstruction was performed
      in 32 patients using the central third of the patellar ligament and in 32
      patients using double-looped semitendinosus and gracilis tendons. All
      reconstructions were performed by a single surgeon, with identical surgical
      technique and rehabilitation protocol. Of the total 64 patients in the study, 54
      (85%) were available for the 5-year follow-up. No statistically significant
      differences were seen with respect to Lysholm score, International Knee
      Documentation Committee (IKDC) classification, clinical and KT-2000 arthrometer
      laxity testing, single-legged hop test and anterior knee pain. Graft rupture
      occurred in two patients (8%) in the patellar tendon group and in two patients
      (7%) in the hamstring tendon group; 23 patients (88%) in the patellar tendon
      group and 23 patients (82%) in the hamstring tendon group returned to their pre
      injury activity level. Good subjective outcome and stability can be obtained by
      using either graft; no statistically significant differences were found in
      functional outcome between the grafts.

PMID- 17431620
TI  - Continuous infusion of insulin-like growth factor-I into the epiphysis of the
      tibia.
AB  - We have developed a method to promote longitudinal bone growth at the level of a
      specific growth-plate (GP) in young rabbits. Insulin-like growth factor-I (IGF-I)
      was continuously infused by means of an osmotic pump into the bone marrow cavity
      of the proximal epiphysis of the tibia. Radiological measurement showed a 2-mm
      overgrowth of the tibia after 4 weeks of treatment, while histological analysis
      demonstrated a 15% increase in the thickness of the selected GP. The local
      infusion of IGF-I increased the numbers of both proliferative and hypertrophic
      chondrocytes and promoted hyperplasia of bony trabeculae within the epiphysis.
      The distribution of material infused locally into the epiphysis was simulated by
      the infusion of Indian ink using the same methodology (osmotic pump) as that for
      IGF-I. Most of the dye remained within the bone marrow cavity of the epiphysis,
      but a portion infiltrated into the GP, reaching the deep layer of the physeal
      chondrocytes and primary spongiosa of the metaphysis. These results suggest that
      the method reported here is a valid one for delivering cytokines or growth
      factors to the selected GP and for controlling the growth and differentiation of
      physeal chondrocytes.

PMID- 17431621
TI  - The four-year functional result after a displaced subcapital hip fracture treated
      with three different surgical options.
AB  - According to the literature, hip function after hip fracture is affected by the
      type of surgery. Our aim was to determine the correlation between surgical
      treatment of hip fracture and postoperative function in the elderly. Inclusion
      criteria were displaced hip fracture and age over 70 years. One hundred and
      twenty-nine participants were randomly divided into three groups according to the
      type of the surgical operation they underwent (hemi-arthroplasty [Merete, Berlin,
      Germany], total arthroplasty [Plus; De Puy, Warsaw, IN, USA] and internal
      fixation [Richards plate screw; Smith & Nephew, Memphis, TN, USA]). The function
      of the patients was estimated using the following parameters: the Barthel Index
      and Harris Hip Score, the range of passive hip motion, the gait speed of
      individuals, after 1 and 4 years of follow-up. The Barthel Index scores after 4
      years of follow-up were 85.3, 82.6, 80.1 after total arthroplasty, hemi
      arthroplasty and internal fixation respectively. Similarly, the Harris Hip Scores
      after 4 years of follow-up were 83.7, 79.5 and 73.6. The range of passive hip
      motion in the three groups of patients did not differ significantly (p>0.05).
      Also, patients of the total arthroplasty and hemi-arthroplasty groups walked
      faster than the patients of the internal fixation group 4 years after discharge
      (p<0.05). In conclusion, we believe that total hip arthroplasty is the treatment
      of choice for displaced subcapital hip fractures in patients over 70 years old.

PMID- 17431622
TI  - Proximal cement fixation in total hip arthroplasty--first results with a new stem
      design.
AB  - Stem loosening and stress-shielding are problems encountered in cemented hip
      arthroplasty. Could proximal stem fixation by partial cementing solve the
      problem? More physiological transmission of forces with only proximal cement
      fixation seems to be possible with this recent development (Z-stem, Option 3000,
      Mathys Orthopaedics, Bettlach, Switzerland). In a prospective clinical trial,
      this new implant was used for total hip arthroplasty in human patients. One
      hundred and thirty-three (133) total hip replacements in 123 patients were
      performed between April 1996 and January 2003. All of them were followed up
      regularly; 53 were analysed with the EBRA-FCA method (Einzel Bild Rontgen Analyse
      -femoral component analysis), whereas the rest were analysed using conventional
      follow-up X-rays. Eighty-six (86) patients with 95 hips could be examined in
      August 2004 to obtain mid-term results. At this stage, the mean follow-up time
      was 61 months (5.08 years), with a maximum of 100 months (8.33 years). Up to
      October 2004, nine cases needed a revision. The clinical data collected reported
      an average Harris Hip Score of 89.3 (good). The EBRA-FCA analysis reported a mean
      subsidence of less than 1.5 mm after the first two years, under the EBRA
      threshold of predicted loosening. At the latest follow-up (at an average of 61
      months), there was an average stable subsidence of 2.4 mm in general. Eight (8)
      patients presented with subsidence of more than 5 mm. The results of the new
      implant seem to be encouraging. Finally, comparing our results to other fixation
      concepts will require longer follow-up periods.

PMID- 17431623
TI  - Repair of spondylolytic defect with a cable screw reconstruction.
AB  - We present the clinical and radiological results of surgical repair for
      refractory spondylolysis in 20 patients at a minimum follow-up of 2 years.
      Seventeen of them were reassessed after 5 years. The Oswestry scores revealed
      good to excellent results in 90% (18/20 patients), indicating a good outcome with
      surgical repair using two techniques: the Scott procedure or pedicle screw and
      wire technique. Radiological pseudarthosis was 10%, which was quite consistent
      with reported series. CT scanning of the 14 patients after a mean of 13 months
      revealed complete healing of the fracture in 7 patients, partial in 2 and frank
      non-union in 5. Overall, CT examination with reversed gantry showed only 7/14
      (50%) healing, indicating that radiological healing on plain X-ray is not always
      suggestive of complete bony healing. However, CT healing is not a sine qua non of
      good to excellent clinical outcome.

PMID- 17431624
TI  - Awareness and use of intertrochanteric osteotomies in current clinical practice.
      An international survey.
AB  - Current literature shows that intertrochanteric osteotomies can produce excellent
      results in selected hip disorders in specific groups of patients. However, it
      appears that this surgical option is considered an historical one that has no
      role to play in modern practice. In order to examine current awareness of and
      views on intertrochanteric osteotomies among international hip surgeons, an
      online survey was carried out. The survey consisted of a set of questions
      regarding current clinical practice and awareness of osteotomies. The second part
      of the survey consisted of five clinical cases and sought to elicit views on
      preoperative radiological investigations and preferred (surgical) treatments. The
      results of our survey showed that most of these experts believe that
      intertrochanteric osteotomies should still be performed in selected cases. Only
      56% perform intertrochanteric osteotomies themselves and of those, only 11%
      perform more than five per year. The responses to the cases show that about 30
      40% recommend intertrochanteric osteotomies in young symptomatic patients. This
      survey shows that the role of intertrochanteric osteotomies is declining in
      clinical practice.

PMID- 17431625
TI  - Successful treatment with voriconazole of Aspergillus meningitis in a patient
      with acute myeloid leukemia.

PMID- 17431626
TI  - Pharmacokinetics of the adrenocorticolytic compounds 3-methylsulphonyl-DDE and
      o,p'-DDD (mitotane) in Minipigs.
AB  - The pharmacokinetics of the adrenocorticolytic drug candidate 3-Methylsulphonyl
      DDE (3-MeSO2-DDE) and the anticancer drug o,p'-DDD (mitotane) were studied in
      Gottingen minipigs. The animals were given 3-MeSO2-DDE or o,p'-DDD as single oral
      doses (30 mg/kg). Concentrations in plasma and subcutaneous fat were measured by
      gas chromatography at different time points during 180 days. Maximal plasma
      concentrations appeared within 24 h for both compounds, but were about 2 times
      higher for 3-MeSO2DDE. o,p'-DDD plasma concentrations declined rapidly to low
      levels during 4 days. 3-MeSO2-DDE also decreased rapidly, but remained at high
      concentrations throughout the study. In fat, 3-MeSO2-DDE reached about 25-fold
      higher levels than o,p'-DDD at 30 days, and both substances were eliminated
      slowly from this tissue. 3-MeSO2-DDE liver concentrations were about 18-fold
      higher than those in plasma at 180 days. In contrast, o,p'-DDD liver and plasma
      levels were about equal at 180 days. o,p'-DDD had roughly 45 times larger CL/F
      than 3-MeSO2-DDE, confirming that the elimination of this compound was more
      rapid. Both compounds were characterised by their localisation and retention in
      fat tissue, and the individual size of the fat stores clearly determined the
      plasma concentrations. It is concluded that although 3-MeSO2-DDE is an
      interesting candidate for therapeutic use due to its potential characteristics to
      specifically target adrenocortical tumour cells the slow elimination of the
      compound might make it challenging to design appropriate dosage regimes.

PMID- 17431627
TI  - [Metastatic placental site trophoblastic tumor. Diagnosis after pneumothorax].
AB  - Placental site trophoblastic tumor (PSTT) is a rare, mostly benign tumor, which
      in 10-15% of cases shows a malignant behavior. The case of a 35 year old woman
      with pulmonary metastasis of a PSTT is reported. This finding was incidental in
      an atypical lung-resection due to pneumothorax. The literature on this rare tumor
      entity is reviewed especially in terms of differential diagnosis, biological
      behavior and association with a pneumothorax.

PMID- 17431628
TI  - [Molecular pathology of epithelial ovarian neoplasias: from the phenotype
      genotype correlation to new targets in diagnostics and therapy].
AB  - Despite the fact that ovarian carcinomas are phenotypically heterogeneous, they
      can be divided into two main groups with common pathogenetic mechanisms. Based on
      clinical, pathological and molecular parameters, a relatively large group of
      tumors can be distinguished with stepwise development from benign precursors and
      borderline tumors to invasive carcinomas (type I). Depending on the morphological
      phenotype, characteristic genetic changes can be observed, such as mutations in
      KRAS and BRAF in serous borderline tumors and low-grade serous carcinomas.
      Mutations in KRAS are also frequently detected in mucinous borderline tumors and
      mucinous carcinomas. The group of endometrioid tumors is characterized by
      mutations in components of the Wnt-signal transduction pathway and PTEN or
      microsatellite instability. The second large group of tumors (type II) includes
      tumors with "de novo" development of highly malignant carcinomas such as the
      conventional (moderately to poorly differentiated) high-grade serous carcinomas,
      undifferentiated carcinomas and malignant mixed mesodermal tumors. These tumors
      are associated with frequent mutations in p53 and complex chromosomal
      alterations. In the future, the combined analysis of morphological parameters,
      genetic changes, gene-expression profiling and protein data will reveal possible
      diagnostic and therapeutic targets for ovarian carcinomas.

PMID- 17431630
TI  - P wave dispersion in patients with rheumatoid arthritis: its relation with
      clinical and echocardiographic parameters.
AB  - P wave dispersion (PWD) is a sign for the prediction of atrial fibrillation (AF).
      The aim of this study was to assess P wave dispersion and its relation with
      clinical and echocardiographic parameters in patients with rheumatoid arthritis
      (RA). Thirty RA patients (mean age 49 +/- 10 years) and 27 healthy controls (mean
      age 47 +/- 8 years) were included in the study. We performed electrocardiography
      and Doppler echocardiography on patients and controls. Maximum and minimum P wave
      duration were obtained from electrocardiographic measurements. PWD defined as the
      difference between maximum and minimum P wave duration was also calculated.
      Maximum P wave duration and PWD was higher in RA patients than controls (P =
      0.031 and P = 0.001, respectively). However, there was no significant difference
      in minimum P wave duration between the two groups (P = 0.152). There was
      significant correlation between PWD and disease duration (r = 0.375, P = 0.009)
      and isovolumetric relaxation time (r = 0.390, P = 0.006). P wave duration and PWD
      was found to be higher in RA patients than healthy control subjects. PWD is
      closely associated with disease duration and left ventricular (LV) diastolic
      dysfunction.

PMID- 17431632
TI  - Micropropagation and germplasm conservation of Central Park Splendor Chinese elm
      (Ulmus parvifolia Jacq. 'A/Ross Central Park') trees.
AB  - Micropropagation offers opportunities to propagate, preserve and ship tree
      germplasm. It also reduces the risk of moving pathogens and insects with the
      germplasm due to built-in pathogen detection capabilities of aseptic cultures.
      For the past few decades, our laboratory has been involved in a project to
      preserve and restore a large, cold hardy, and historically important Chinese elm
      (Ulmus parvifolia Jacq. 'A/Ross Central Park') tree. Here we present three simple
      and efficient systems for its micropropagation, germplasm conservation and
      distribution: (1) in vitro plant formation from meristematic nodules (MNs), (2)
      plantlet generation from axillary buds, and (3) in vitro rooting of micro
      cuttings from 20-years-old hedged stock plants. Newly flushed nodal segments were
      used as explants. WPM with 0.5 mg/l BA was found to be the best medium for
      meristematic shoot development and WPM supplemented with 2.0 mg/l 4-CPPU and 0.5
      mg/l TDZ was best for meristematic nodule formation. Rhizogenesis of regenerants
      and micro-cuttings was best achieved on WPM with 1.0 mg/l NAA and 2% sucrose.
      Rooted plants were readily acclimatized to the greenhouse ambient environment and
      continued to grow well under greenhouse conditions. The survival rate of
      acclimatized plantlets under ex vitro conditions was 100% after 4 weeks. Plants
      looked healthy with no visually detectable phenotypic variation based on
      observation of about 1,000 plants. Cycling of shoot explants and MNs through
      repetitive cultures was effective in scaling-up propagules.

PMID- 17431633
TI  - The seasonal activity and the effect of mechanical bending and wounding on the
      PtCOMT promoter in Betula pendula Roth.
AB  - In this study, 900-bp (signed as p including nucleotides -1 to -886) and partly
      deleted (signed as dp including nucleotides -1 to -414) COMT (caffeate/5
      hydroxyferulate O-methyltransferase) promoters from Populus tremuloides Michx.
      were fused to the GUS reporter gene, and the tissue-specific expression patterns
      of the promoters were determined in Betula pendula Roth along the growing season,
      and as a response to mechanical bending and wounding. The main activity of the
      PtCOMTp- and PtCOMTdp-promoters, determined by the histochemical GUS assay, was
      found in the developing xylem of stems during the 8th-13th week and in the
      developing xylem of roots in the 13th week of the growing season. The GUS
      expression patterns did not differ among the xylem cell types. The PtCOMT
      promoter-induced GUS expression observed in phloem fibres suggests a need for
      PtCOMT expression and thus syringyl (S) lignin synthesis in fibre lignification.
      However, the PtCOMTdp-promoter induced GUS expression in stem trichomes, which
      may contribute to the biosynthesis of phenylpropanoid pathway-derived compounds
      other than lignin. Finally, a strong GUS expression was induced by the PtCOMT
      promoters in response to mechanical stem bending but not to wounding. The lack of
      major differences between the PtCOMTp- and PtCOMTdp-promoters suggests that the
      deleted promoter sequence (including nucleotides -415 to -886) did not contain a
      significant regulatory element contributing to the GUS expression in young B.
      pendula trees.

PMID- 17431631
TI  - Molecular genetic improvement of cereals: transgenic wheat (Triticum aestivum
      L.).
AB  - Only modest progress has been made in the molecular genetic improvement of wheat
      following the production of the first transgenic plants in 1992, made possible by
      the development of efficient, long-term regenerable embryogenic cultures derived
      from immature embryos and use of the biolistics method for the direct delivery of
      DNA into regenerable cells. Transgenic lines expressing genes that confer
      resistance to environmentally friendly non-selective herbicides, and pests and
      pathogens have been produced, in addition to lines with improved bread-making and
      nutritional qualities; some of these are ready for commercial production.
      Reduction of losses caused by weeds, pests and pathogens in such plants not only
      indirectly increases available arable land and fresh water supplies, but also
      conserves energy and natural resources. Nevertheless, the work carried out thus
      far can be considered only the beginning, as many difficult tasks lie ahead and
      much remains to be done. The challenge now is to produce higher-yielding
      varieties that are more nutritious, and are resistant or tolerant to a wide
      variety of biotic as well as abiotic stresses (especially drought, salinity,
      heavy metal toxicity) that currently cause substantial losses in productivity.
      How well we will meet this challenge for wheat, and indeed for other cereal and
      non-cereal crops, will depend largely on establishing collaborative partnerships
      between breeders, molecular biologists, biotechnologists and industry, and on how
      effectively they make use of the knowledge and insights gained from basic studies
      in plant biology and genetics, the sequencing of plant/cereal genomes, the
      discovery of synteny in cereals, and the availability of DNA-based markers and
      increasingly detailed chromosomal maps.

PMID- 17431634
TI  - [Failure to thrive in an 8-month-old child with unilateral ocular reddening and
      iris alterations].

PMID- 17431629
TI  - Thioredoxins in chloroplasts.
AB  - Thioredoxins (TRXs) are small disulfide oxidoreductases of ca. 12 kDa found in
      all free living organisms. In plants, two chloroplastic TRXs, named TRX f and TRX
      m, were originally identified as light dependent regulators of several carbon
      metabolism enzymes including Calvin cycle enzymes. The availability of genome
      sequences revealed an unsuspected multiplicity of TRXs in photosynthetic
      eukaryotes, including new chloroplastic TRX types. Moreover, proteomic approaches
      and focused studies allowed identification of 90 potential chloroplastic TRX
      targets. Lately, recent studies suggest the existence of a complex interplay
      between TRXs and other redox regulators such as glutaredoxins (GRXs) or
      glutathione. The latter is involved in a post-translational modification, named
      glutathionylation that could be controlled by GRXs. Glutathionylation appears to
      specifically affect the activity of TRX f and other chloroplastic enzymes and
      could thereby constitute a previously undescribed regulatory mechanism of
      photosynthetic metabolism under oxidative stress. After summarizing the initial
      studies on TRX f and TRX m, this review will focus on the most recent
      developments with special emphasis on the contributions of genomics and
      proteomics to the field of TRXs. Finally, new emerging interactions with other
      redox signaling pathways and perspectives for future studies will also be
      discussed.

PMID- 17431635
TI  - [Bilateral papilledema].

PMID- 17431636
TI  - [Slowly growing lid tumor].

PMID- 17431637
TI  - [Unexpected foreign bodies in eyelid surgery. Three cases of unexplained lid
      tumors].
AB  - Foreign bodies are quite commonly found incorporated in the lid area after
      injuries. Normally the patient's description of the injury and the usually fresh
      clinical findings leave little room for doubt about their composition. In
      isolated cases, however, patients are admitted with "lid tumors" following an
      accident in the rather distant past, so that sometimes no connection can be seen
      with the symptoms present on admission and it is not even clear whether there is
      still foreign material in the wound. Subcutaneous swellings can then easily be
      mistaken for cicatricial tissue, granulomas or old hematomas. In all these cases
      there can be a big difference between what the surgeon expects and the actual
      intraoperative findings. We present three cases in which unexpected foreign
      bodies have been extracted from the eyelid region.

PMID- 17431638
TI  - Physiology and antennal lobe projections of olfactory receptor neurons from
      sexually isomorphic sensilla on male Heliothis virescens.
AB  - The neurophysiology and antennal lobe projections of olfactory receptor neurons
      (ORNs) within sexually isomorphic short trichoid sensilla of male Heliothis
      virescens (Noctuidae: Lepidoptera) were investigated using cut-sensillum
      recording and cobalt-lysine staining. A total of 202 sensilla were sorted into 14
      possible sensillar categories based on odor responses and physiology of ORNs
      within. Seventy-two percent of the sensilla identified contained ORNs stimulated
      by conspecific odors. In addition, a large number of ORNs were specifically
      sensitive to ss-caryophyllene, a plant-derived volatile (N = 41). Axons
      originating from ORNs associated with individual sensilla were stained with
      cobalt lysine (N = 67) and traced to individual glomeruli in the antennal lobe.
      ORNs with responses to female sex pheromone components exhibited similar axonal
      projections as those previously described from ORNs in long sensilla trichodea in
      male H. virescens. Antennal lobe axonal arborizations of ORNs sensitive to
      hairpencil components were also located in glomeruli near the base of the
      antennal nerve, whilst those sensitive to plant odorants projected to more medial
      glomeruli. Comparisons with ORNs described from female H. virescens supports the
      notion that glomeruli at the base of the antennal nerve are associated with
      conspecific and interspecific odorants, whereas those located medially are
      associated with plant volatiles.

PMID- 17431639
TI  - Neuroethology of ultrasonic hearing in nocturnal butterflies (Hedyloidea).
AB  - Nocturnal Hedyloidea butterflies possess ultrasound-sensitive ears that mediate
      evasive flight maneuvers. Tympanal ear morphology, auditory physiology and
      behavioural responses to ultrasound are described for Macrosoma heliconiaria, and
      evidence for hearing is described for eight other hedylid species. The ear is
      formed by modifications of the cubital and subcostal veins at the forewing base,
      where the thin (1-3 microm), ovoid (520 x 220 microm) tympanal membrane occurs in
      a cavity. The ear is innervated by nerve IIN1c, with three chordotonal organs
      attaching to separate regions of the tympanal membrane. Extracellular recordings
      from IIN1c reveal sensory responses to ultrasonic (>20 kHz), but not low
      frequency (<10 kHz) sounds. Hearing is broadly tuned to frequencies between 40
      and 80 kHz, with best thresholds around 60 dB SPL. Free flying butterflies
      exposed to ultrasound exhibit a variety of evasive maneuvers, characterized by
      sudden and unpredictable changes in direction, increased velocity, and durations
      of approximately 500 ms. Hedylid hearing is compared to that of several other
      insects that have independently evolved ears for the same purpose-bat detection.
      Hedylid hearing may also represent an interesting example of evolutionary
      divergence, since we demonstrate that the ears are homologous to low frequency
      ears in some diurnal Nymphalidae butterflies.

PMID- 17431640
TI  - Metabolic and respiratory status of cold-stunned Kemp's ridley sea turtles
      (Lepidochelys kempii).
AB  - "Cold-stunning" of sea turtles has been reported as a naturally occurring
      stressor for many years; however, the physiologic status of cold-stunned turtles
      has only been partially described. This study investigated initial and
      convalescent venous blood gas, acid-base, and critical plasma biochemical data
      for 26 naturally cold-stunned Kemp's ridley sea turtles (Lepidochelys kempii)
      from Cape Cod, MA, USA. Samples were analyzed for pH, pCO(2), pO(2), bicarbonate,
      plasma osmolality, sodium, potassium, chloride, ionized calcium, ionized
      magnesium, glucose, lactate, and blood urea nitrogen using a clinical point-of
      care analyzer. Data were corrected for the patient's body temperature using both
      species-specific and more general correction methods. In general, venous blood
      gas, acid-base, and plasma biochemical data obtained for surviving cold-stunned
      Kemp's ridley sea turtles were consistent with previously documented data for sea
      turtles exposed to a wide range of temperatures and physiologic stressors. Data
      indicated that turtles were initially affected by metabolic and respiratory
      acidosis. Initial pH-corrected ionized calcium concentrations were lower than
      convalescent concentrations, and initial pH-corrected ionized magnesium
      concentrations were higher than convalescent concentrations.

PMID- 17431641
TI  - Effects of ouabain on proliferation, intracellular free calcium and c-myc mRNA
      expression in vascular smooth muscle cells.
AB  - Ouabain, a newly discovered mammalian steroid hormone, has been shown to
      correlate directly with mean blood pressure. In the present study, the mechanism
      by which ouabain may act on blood pressure was investigated using primary
      cultures of bovine vascular smooth muscle cells. 3-[4,5-Dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide (MTT) assay showed a biphasic effect on cell
      proliferation: at low concentrations ouabain stimulated cell growth while at
      higher concentrations it inhibited cell growth, which is similar to angiotensin
      II, an octapeptide hormone. Confocal laser scanning microscopy assay also
      indicated a biphasic nature on intracellular free calcium, which was decreased by
      low concentration of ouabain and increased by higher concentration of ouabain.
      Simultaneously, an increase of c-myc mRNA expression by low concentration of
      ouabain was obtained with reverse transcription-polymerase chain reaction (RT
      PCR) assay. It is important to note that the low concentrations (10(-15)-10(-12)
      M) are under the normal circulating levels (2.5-8.0 x 10(-11) M) of endogenous
      ouabain. These results suggest that ouabain-induced proliferation might be
      attributed, at least in part, to the decrease of intracellular free calcium and
      the increase of c-myc mRNA expression, and that may be directly or indirectly
      involved in the regulation of blood pressure.

PMID- 17431643
TI  - Amyloid precursor protein cytoplasmic domain with phospho-Thr668 accumulates in
      Alzheimer's disease and its transgenic models: a role to mediate interaction of
      Abeta and tau.
AB  - Abnormal accumulation of Abeta and tau in senile plaques (SP) and neurofibrillary
      tangles (NFTs) is a key event in Alzheimer's disease (AD). Here, we show that
      T668-phosphorylated cytoplasmic domain of APP (pT668-ACD) accumulates Abeta and
      tau in AD and its transgenic models. Anti-pT668 immunostaining of AD brain
      sections with hydrated autoclave enhancement identified SP neurites and NFTs in
      which pT668-ACD colocalizes with tau. We produced and examined transgenic (Tg)
      mice that overexpress human APP695, harboring the double Swedish/London mutation,
      and develop age-dependently Abeta plaques in the brain. All Abeta plaques contain
      co-accumulations of pT668-ACD, but co-accumulation of tau appears in only a
      fraction of Abeta plaques in older animals. We also examined the established tau
      Tg mice that overexpress the smallest human brain tau isoform and develop
      neuronal accumulations of tau in older animals. Examination of the old tau Tg
      mice showed that neuronal cells affected by tau accumulation induce co
      accumulation of pT668-ACD. We speculate that in AD brains, extracellular Abeta
      deposition is accompanied by intracellular accumulation of pT668-ACD, followed by
      tau accumulation in the SP with dystrophic neurites and that neuronal cells
      affected by tau accumulation induce co-accumulation of pT668-ACD in NFTs. Thus,
      pT668-ACD is likely to mediate pathological interaction between Abeta and tau.

PMID- 17431642
TI  - Orchidopexy and its impact on fertility.
AB  - We critically analysed the factors known to influence the fertility potential
      after orchidopexy in children. A comprehensive literature review of all
      publications in the English language listed in Medline using the words
      cryptorchidism, undescended testis, orchidopexy, fertility, semen analysis and
      surgery from 1970 to 2005. In unilateral ectopic, canalicular and emergent
      testes, as long as the surgery is carried out in early childhood, fertility
      outcome is good (>90%). The majority of the bilateral abdominal testes are
      infertile. While unilateral abdominal testes and unilateral absent or vanishing
      testes have favourable fertility potential, quantification has proven difficult.
      Despite multiple studies, fertility in crypt orchid tests is still an uncertain
      issue. Hormonal treatment in conjunction with early surgical correction has not
      been fully explored. We recommend orchidopexy soon after 6-7 months of age,
      corrected for term, to maximise the future fertility potential.

PMID- 17431644
TI  - Molecular array analyses of 51 pediatric tumors shows overlap between malignant
      intracranial ectomesenchymoma and MPNST but not medulloblastoma or atypical
      teratoid rhabdoid tumor.
AB  - Gene microarray has been used to identify prognostic markers and genes of
      interest for therapeutic targets; a less common use is to show possible
      histogenetic relationships between rare tumor types and more common neoplasms.
      Intracranial malignant ectomesenchymoma (MEM) is a pediatric tumor postulated to
      arise from neural crest cells that contain divergent neuroectodermal and
      mesenchymal tissues, principally mature ganglion cells and rhabdomyosarcoma
      (RMS). We investigated a case of MEM by molecular, cytogenetic, and gene array
      analyses and compared results with our previously unpublished series of 51
      pediatric tumors including conventional RMS, Ewing sarcoma (EWS), medulloblastoma
      (MED), atypical teratoid rhabdoid tumor (ATRT), and malignant peripheral nerve
      sheath tumor (MPNST); the latter is a sarcoma also with potential for divergent
      differentiation. Standard cytogenetic analyses and RT-PCR testing for the classic
      gene rearrangements seen in RMS [t(2;13)-PAX3/FKHR] and EWS ([t(11;22) & t(21;22)
      EWS/FLI-1 & EWS/ERG), were used for characterization of the MEM, with gene
      expression microarray analyses on all tumor types. Gene rearrangement studies
      were negative in MEM. Gene expression microarray analyses showed tight clustering
      of the MEM with the MPNST (n = 2), but divergence from other pediatric tumors.
      MEM and MPNST both showed complex karyotypes, but without diagnostic
      translocations. Despite the presence of malignant skeletal muscle differentiation
      in the MEM, gene array testing showed no overlap with RMS, MED, or ATRT, but
      rather with MPNST. This suggests a common stem cell origin or embryonic gene
      recapitulation for these tumors and provides novel insights into their underlying
      biology.

PMID- 17431645
TI  - Cellular localization of pituitary adenylate cyclase-activating peptide (PACAP)
      following traumatic brain injury in humans.
AB  - The pituitary adenylate cyclase-activating peptide (PACAP) is involved in many
      processes of the developing and mature central nervous system, such as
      proliferation, differentiation, apoptosis, neurotransmission, inflammation and
      neuroprotection. Alternative posttranslational processing of PACAP results in two
      biologically active, amidated 27- and 38-amino acid peptides termed PACAP27 and
      PACAP38. In the present study, we examined whether traumatic brain injury (TBI)
      affects cellular immunopositivity for PACAP27 and PACAP38. Patients (n = 55) were
      classified into three groups dependent on their survival time (under 24 h,
      between 24 h and 7 days and between 7 days and 99 days postinjury). PACAP27 and
      PACAP38 were expressed by neurons and glial cells in normal human neocortex (n =
      10). Following TBI, the total number of PACAP27- and PACAP38-positive cells was
      significantly decreased for a prolonged survival period within the traumatized
      neocortex. In the pericontusional cortex, the number of cells expressing PACAP27
      and PACAP38 was significantly increased at all survival times examined. Triple
      immunofluorescence examinations revealed a significant increase in the absolute
      numbers of GFAP-positive reactive astrocytes as well as a decrease in the CNP
      positive oligodendrocytes, each coexpressing PACAP27 or PACAP38 in the
      contusional and pericontusional cortex. We hypothesize that the increase of glial
      PACAP immunoreactivity may be interpreted as part of a complex endogenous
      neuroprotective response in the pericontusional regions, but the precise role of
      PACAP following TBI is yet to be determined.

PMID- 17431646
TI  - Chronic ethanol exposure causes mitochondrial dysfunction and oxidative stress in
      immature central nervous system neurons.
AB  - Cerebellar hypoplasia in experimental fetal alcohol syndrome (FAS) is associated
      with impaired insulin-stimulated survival signaling. In vitro studies
      demonstrated that ethanol inhibition of neuronal survival is mediated by
      apoptosis and mitochondrial dysfunction. Since insulin and insulin-like growth
      factors (IGFs) regulate energy metabolism, and ethanol can exert its toxic
      effects by causing oxidative damage to DNA and proteins, we further characterized
      the effects of chronic gestational exposure to ethanol on mitochondrial gene
      expression, and the degree to which ethanol inhibition of mitochondrial function
      is mediated by impaired insulin/IGF responsiveness. Pregnant Long-Evans rats were
      fed isocaloric liquid diets containing 0, 2, 4.5, 6.5, or 9.25% v/v ethanol from
      gestation day 6 through delivery. Cerebella harvested on postnatal day 1 were
      examined for indices of oxidative stress, and mRNA levels of mitochondrial, pro
      oxidant, and pro-apoptosis gene expression. Rat primary cerebellar neuron
      cultures were used to characterize the effects of ethanol (50 mM for 96 h) on
      insulin and IGF stimulated mitochondrial function and ATP production. Ethanol
      exposed cerebella had significantly reduced mRNA levels of mitochondrial genes
      encoding Complexes II-A, IV, and V, increased expression of p53 and NADPH oxidase
      (NOX) 1 and 3, and increased immunoreactivity for 4-hydroxy-2,3-nonenal (HNE) and
      8-OHdG in cerebellar granule cells. The activations of p53 and NOX genes were
      highest in cerebella from pups exposed to the 6.5 or 9.25% ethanol containing
      diet, whereas the impairments in mitochondrial Complex IV and V expression were
      similar at low and high levels of ethanol exposure. In vitro experiments
      confirmed that ethanol treatment reduces neuronal expression of mitochondrial
      genes encoding Complexes IV and V, impairs mitochondrial function and ATP
      production, and increases HNE and 8-OHdG immunoreactivity, but they also showed
      that these effects were not insulin- or IGF-dependent. Together, the results
      suggest that mitochondrial dysfunction, oxidative stress, and DNA damage in FAS
      may be largely due to the toxic effects of ethanol rather than specific
      impairments in insulin or IGF signaling.

PMID- 17431647
TI  - Intraperitoneal injection of pemphigus vulgaris-IgG into mouse depletes epidermal
      keratinocytes of desmoglein 3 associated with generation of acantholysis.
AB  - Pemphigus vulgaris is an autoimmune blistering disease caused by antibodies
      against desmoglein (Dsg) 3. We previously reported that pemphigus vulgaris (PV)
      IgG caused the formation of Dsg3-depleted desmosomes in normal human cultured
      keratinocytes and DJM-1, a human squamous cell carcinoma cell line. In the
      present study, we injected PV-IgG and normal human IgG into neonatal mice and
      examined the quantities of Dsg3 in the mouse skin. We showed that injection of PV
      IgG into neonatal mice caused suprabasal blister formation and approximately 30%
      reduction of Dsg3 in mouse epidermal keratinocytes, compared to mice injected
      with normal human IgG. In addition, we showed that the quantity of Dsg3 in the
      skin of patients with PV did decrease, as compared to that in healthy volunteers.
      Our data suggests the reduction of Dsg3 might be relevant to blister formation.
      These results also suggest that even a partial depletion of Dsg3 may contribute
      to blistering in PV patients.

PMID- 17431648
TI  - Three-dimensional ultrasound fetal urinary bladder volume measurement:
      reliability of rotational (VOCAL) technique using different steps of rotation.
AB  - OBJECTIVE: The aim of the study was to investigate the inter- and intraobserver
      reliability in measuring the fetal bladder volume by 3d ultrasound imaging by
      VOCAL. In addition a comparison of 15 degrees and 30 degrees rotation steps
      calculation had been performed. METHODS: Measurements (n = 240) of FB volume were
      performed in 30 low-risk patients with gestation times ranging from 22 to 39
      weeks by two independent observers blind to each other. All fetuses were examined
      and no ultrasound detectable malformation was found. The volume for each FB was
      measured twice by the observers who used the Virtual Organ Computed-aided
      Analysis (VOCAL) technique. Distinct sets of 12 and 6 planes were obtained after
      sequential rotations of 15 degrees and 30 degrees, respectively. The internal
      contour of fetal bladder was determined manually and carefully as to exclude
      adjacent structures from volume calculation. Wilcoxon signed-rank test was used
      for the comparison of paired samples in the cases of replication within and
      between observers. Spearman's rank correlation was used to study the relationship
      among angles. Bland and Altman's graphical approach was used to investigate the
      agreement between observers. RESULTS: Both techniques were shown to be highly
      reliable. No significant difference was found between the measurements of FB
      volume with the VOCAL technique by varying either the steps of rotation or the
      observers. CONCLUSION: Excellent correlations were found for both observers in
      the use of rotation angles of 15 degrees and 30 degrees . Since a significantly
      faster evaluation was obtained by using a 30 degrees rotation step it must be
      preferred to assess the FB volume. Our results show that the VOCAL technique,
      with a plane rotation of 30 degrees , can be used in a simple way to estimate
      fetal urine production.

PMID- 17431649
TI  - Elevated level of cell-free plasma DNA is associated with breast cancer.
AB  - BACKGROUND: We analysed cell-free DNA (cfDNA) in the plasma of patients with both
      malignant and benign breast lesions by real-time quantitative PCR to determine
      whether the finding may have diagnostic and prognostic implications. METHODS:
      Plasma samples were obtained from 33 patients with breast cancer, 32 patients
      with benign breast lesions and 50 healthy women as normal controls. Circulatory
      cfDNA was extracted from the plasma samples and quantified by real-time
      quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene.
      RESULTS: The mean concentrations of cfDNA in the plasma samples from patients
      with breast cancer, patients with benign breast lesions and normal controls were
      2,285, 1,368 and 1,489 genome equivalents (GE) per millilitre, respectively. The
      level of cfDNA in the breast cancer group was significantly higher than those in
      the benign lesion group and control group (P = 0.007 and 0.013, respectively).
      These findings were associated with malignant tumour size. The levels of the
      cfDNA were high in patients with lymph node involvement and distant metastasis.
      CONCLUSIONS: Our results suggest that levels of cfDNA in the plasma are elevated
      in malignant breast cancer and correlated with tumour size. These findings could
      have diagnostic and prognostic value for malignant breast tumours.

PMID- 17431650
TI  - Laparoscopic procedures during pregnancy and the risks of anesthesia: what does
      an obstetrician need to know?
AB  - BACKGROUND: Nonobstetric surgery may be necessary during any stage of gestation.
      METHODS: The purpose of this article is to review the current recommendations
      (using Medline search for the relevant publications) for the perioperative
      anesthetic management of pregnant women undergoing laparoscopy for indications
      unrelated to pregnancy. RESULTS: The current estimates of the incidence of
      nonobstetric surgery in pregnancy range from 1% to 2%. Laparoscopy is the most
      common surgical procedure performed in the first trimester of pregnancy, whereas
      appendectomy is the most common procedure performed during the remainder of
      pregnancy. CONCLUSIONS: In the past pregnancy was considered as an absolute
      contraindication to laparoscopy. However, recent years have brought an extensive
      experience with this technique during gestation.

PMID- 17431651
TI  - Unique case of successful twin pregnancy after spontaneous conception in a
      patient with uterus bicornis unicollis.
AB  - INTRODUCTION: Abnormal fusion of the mullerian ducts or failure of absorption of
      the septum causes varying degrees of congenital uterine malformation. Twin
      gestation in a case of bicornuate uterus is extremely rare. We are reporting this
      case because of its extremely rare presentation, where twins have managed to
      reach term after spontaneous conception. CASE REPORT: A 28-year-old second
      gravida, para one was initially diagnosed to have diamniotic dichorionic twins on
      ultrasound. At term, she was referred to us with severe preeclamptic toxaemia. On
      examination, she was found to have a bicornuate uterus with one fetus in each
      horn. Both siblings were successfully delivered by caesarean section. So far,
      only one similar case has been reported following in vitro fertilisation.
      CONCLUSION: Although poor reproductive performance has been documented in
      previous reports of bicornuate uterus with twin gestation, our patient managed to
      reach term with delivery of healthy siblings by caesarean section.

PMID- 17431652
TI  - Management of extra-tubal and rare ectopic pregnancies: case series and review of
      current literature.
AB  - OBJECTIVE: Management of extra-tubal ectopic gestations remains an inadequately
      explored clinical field due to the rarity of the presentations. We present a
      synopsis of the management highlighted by our personal case series. METHOD: A
      literature search was conducted through Pubmed and Medline databases. We reviewed
      all cases presenting with extra-tubal nidations in our institute, including seven
      interstitial, two cervical, three ovarian and two abdominal pregnancies. RESULT:
      The advances in minimal access techniques and imaging modalities have resulted in
      novel fertility preserving endoscopic procedures. All except one of the patients
      were treated by endoscopic procedures, including a novel procedure for evacuation
      of cornual ectopics. CONCLUSION: A high index of suspicion is essential, combined
      with meticulous review of clinical findings and imaging modalities to make an
      accurate diagnosis. Treatment with the least invasive method, either by minimal
      access techniques, non-invasive radiological procedures or medical treatment
      should be encouraged.

PMID- 17431653
TI  - One-year follow-up results of combined use of CO2 laser and cold instrumentation
      for Reinke's edema surgery in professional voice users.
AB  - The purpose of this study was to present our experience with combined use of CO2
      laser and cold instrumentation for Reinke's edema surgery and to evaluate 1-year
      follow-up results of the technique in a series of professional voice users.
      Fifteen patients with Reinke's edema who underwent microlaryngoscopic surgery
      were included. Videolaryngostroboscopy, perceptual and acoustic voice analyses
      were performed before and after surgery. During the 1-year follow-up, no
      recurrence of Reinke's edema was encountered. Significant postoperative
      improvement was obtained in the quality of voice, in terms of GRBAS scores, Fo,
      jitter, shimmer and NHR. No evidence of laryngeal cancer was found on the
      histological examinations. Combined use of CO2 laser and cold instrumentation
      provides a reliable and safe method for Reinke's edema surgery, and cessation of
      smoking, voice rest and control of the laryngopharyngeal reflux contribute to the
      success of surgery. We consider that the removal of redundant mucosa of the vocal
      fold reduces the risk of the recurrence of Reinke's edema and provides better
      quality of voice. However, it does not imply that our method is superior to
      others', but this procedure constitutes an effective treatment of choice for
      Reinke's edema patients, including professional voice users.

PMID- 17431654
TI  - Cervical sympathetic schwannoma with postoperative first bite syndrome.
AB  - Extracranial schwannomas occurring in the head and neck region may arise from
      cranial, peripheral or autonomic nerves. Determination of the nerve of origin is
      not often made until the time of surgery. Schwannomas arising from the cervical
      sympathetic chain are extremely rare. These interesting tumors along with
      schwannomas in general and the remaining class of neurogenic tumors are known for
      their ability to mimic the physical and radiological findings of carotid body
      tumors. Surgery is the treatment of choice and major complications are
      infrequent. However, we report a case of cervical sympathetic chain schwannoma
      with postoperative first bite syndrome.

PMID- 17431655
TI  - Endolaryngeal cordectomy using cold instruments for treatment of T1 glottic
      cancers.
AB  - In the treatment of early-stage glottic cancers, radiotherapy and surgery have
      similar success rates. In our department, we have been using cold instruments
      coupled with surgical microscope and/or telescopes for several years in treatment
      of early stage glottic cancers. Our aims were, to present our experience with
      endolaryngeal resection of T1 glottic cancers with cold instruments coupled with
      surgical microscope and telescopes, to present our oncological results, to
      discuss the advantages of endolaryngeal cordectomy over open cordectomy or RT and
      to discuss whether laser is obligatory for this approach or not. Our study
      includes retrospective analysis of 38 patients with T1 glottic cancer, who have
      been treated with endolaryngeal surgery as the primary treatment. The median
      follow-up was 24 months. The most commonly performed procedure was type-II
      cordectomy (38.5%). Overall survival rate was 94.7%, while the disease-specific
      survival rate was 100%. Local recurrences occurred in two patients at 8th and
      11th months, postoperatively. In the first patient, type-Vc cordectomy and in the
      second type-Va cordectomy had been performed. Both patients with recurrences
      could be salvaged by fronto-lateral laryngectomy, and are still alive in their
      38th and 6th months following salvage surgery. Therefore, the local control rate
      and larynx preservation rate with endolaryngeal cordectomy were 94.7 and 100%,
      respectively, in this study group. All patients had a voice quality sufficient
      for communicating easily over telephone. We believe that lasers are not
      obligatory to perform endolaryngeal cordectomy for treatment of T1 glottic
      cancers, as the same oncological and similar functional outcomes may be achieved
      with the traditional cold instruments.

PMID- 17431656
TI  - The effect of topical insulin application on the healing of acute tympanic
      membrane perforations: a histopathologic study.
AB  - The aim of the present study was to investigate the effects of insulin on the
      healing of acute traumatic tympanic membrane (TM) perforations by observing the
      duration of perforation closure clinically and by examining the TM thickness,
      fibroblastic reaction, neovascularization and collagenization histologically. In
      all, 24 adult healthy guinea pigs were used. TM perforations, about 2 mm in
      diameter were made in the pars tensa of each ear. The perforations in the right
      ears of the guinea pigs (study group) were treated with 1 IU of regular insulin
      (Humulin-R 100 IU/ml, Lilly) daily topically. The left ears of the guinea pigs
      (control group) were treated with saline solution daily. The treatments were
      continued until the each perforation closed. The animals were examined with
      otomicroscopy at first, third, fifth and seventh days. TM specimens were obtained
      after the animals were decapitated under deep anesthesia by an intraperitoneal
      injection of sodium pentobarbital (0.5 ml/100 g) 3 and 7 days after wounding.
      Histologically, the epithelial and mucosal layers were examined. Finger-like
      projections, the edema of the LP, neovascularization of LP, fibroblastic activity
      of LP, inflammatory cell presence of LP, collagenization ratios of LP were
      evaluated. In the study group; LP fibroblastic reaction positivity and LP
      collagenization positivity was significantly higher than the control group (P <
      0.001 and P < 0.05). Topical insulin treatment may be more beneficial in the
      treatment of atrophic membrane, which is a sequel of perforation, when tried in
      various dosages and time intervals.

PMID- 17431657
TI  - Role of fine needle aspiration and frozen section in determining the extent of
      thyroidectomy.
AB  - The routine use of fine needle aspiration (FNA) and frozen section (FS) in the
      management of a thyroid nodule is controversial and needs to be evaluated on an
      institution to institution basis. Our aim was to determine the role of FNA and FS
      in determining the extent of thyroidectomy. We performed a comparative study of
      FNA and FS examination of all patients presenting with nodular thyroid disease
      between September 2002 and December 2005. Data were collected on a proforma by
      reviewing FNA, FS and histopathological reports. Data were analyzed on SPSS 11.
      Sensitivity, specificity, accuracy, positive predictive value and negative
      predictive values were calculated. We included 44 patients with preoperative FNA,
      intraoperative FS examination and final histopathology reports available. We
      excluded patients with local invasion and distant metastases. Final
      histopathological report was taken as gold standard. FNA reported 8 benign, 7
      papillary carcinoma, 22 follicular neoplasm, 1 medullary and 6 suspicious
      lesions. On final pathology there were 16 benign and 28 malignant cases. Thus a
      total of 20 carcinomas were missed by FNA. When routine FS was done, a total of
      ten patients who had malignancy were missed. Both FNA and FS have high
      specificity for diagnosis of thyroid cancer but lacked sensitivity at our
      institution. This is mainly because of high false negative results.

PMID- 17431658
TI  - Comparative outcomes of endoscopic sinus surgery in patients with chronic
      sinusitis and nasal polyps.
AB  - This study was carried out to compare the outcomes of endoscopic sinus surgery in
      patients with chronic sinusitis without nasal polyps (CRS) and those with nasal
      polyps (NP). We also sought to determine the correlation between preoperative
      computed tomography (CT) findings and postoperative endoscopy and symptom score
      improvement. Data were collected from two groups of patients diagnosed as CRS
      with and without nasal polyps that underwent functional endoscopic sinus surgery
      with a 1-year postoperative follow up. Preoperative symptoms, CT scores, and
      endoscopic scores were recorded. Postoperative symptom and endoscopic scores were
      recorded at 1, 6, and 12 months. Assessment of symptoms was performed
      subjectively using visual analogue scoring (VAS). CT scan findings were scored
      using the Lund-Mackay system. Endoscopic examination findings were scored
      according to the staging system proposed by Lanza and Kennedy. The correlations
      between the CT score, endoscopic scores and VAS scores were calculated. There was
      a statistically significant correlation between the preoperative CT, symptom, and
      endoscopic scores. Postoperative symptom and endoscopic scores also showed a
      significant correlation. Total CT scores of the CRS group were significantly
      lower than the scores of the NP group. Also preoperative endoscopy and symptom
      scores were statistically lower in CRS group compared to NP group. Endoscopy
      total scores and symptom total scores of both groups were significantly decreased
      at postoperative 12th month. Statistically significant difference was observed
      between the preoperative and postoperative symptom and endoscopy scores. The
      patients with polyps had higher symptom scores and worse objective findings
      compared to the patients with CRS. In all patients groups, objective and
      subjective scores seemed to correlate well preoperatively and postoperatively.
      These data suggest that endoscopic sinus surgery provides significant symptomatic
      relief and endoscopic healing in patients with CRS and NP.

PMID- 17431659
TI  - The role of interleukin-16 in eosinophilic chronic rhinosinusitis.
AB  - Eosinophilic granulocytes (Eos) are found in great numbers both in the tissue and
      in the mucus of patients suffering from chronic rhinosinusitis with polyposis
      (ECRS). Interleukin-16 (IL-16) is known as a highly potent chemotactic and
      chemoattractant molecule (ED 10-11) for Eos. In an open, explorative, controlled
      study we examined the presence of IL-16 in mucosa tissue, mucus and serum in
      patients suffering from ECRS and its association to Eos activation. Tissue and
      nasal mucus specimen from 10 previously untreated, non allergic ECRS-patients
      undergoing paranasal sinus surgery and from 10 healthy non sinusitis subjects,
      undergoing nasal surgery because of anatomic nasal obstruction were investigated
      by real-time (RT-) PCR targeting human IL-16 mRNA. Haematoxylin-eosin (HE)
      staining and immunohistochemistry of formalin embedded tissue and mucus were
      applied for detection and determination of the proportion of activated Eos (aEos)
      and IL-16. Serum IL-16 was analyzed by enzyme-linked-immunosorbent assay (ELISA).
      IL-16 mRNA and IL-16 protein levels were elevated in nasal mucus, polyp tissue
      and in the serum of ECRS patients compared to healthy controls. There was a high
      proportion of aEos in ECRS patients compared to healthy subjects. Serum IL-16, IL
      16 mRNA expression and IL-16 protein in mucus and tissue specimens were
      significantly associated with the presence of aEos in polyps of ECRS patients.
      Immunohistochemically IL-16 protein was mainly expressed in aEos, mast cells,
      lymphocytes and epithelial cells. In conclusion our data indicate that IL-16 may
      stimulate the migration and persistence of activated Eos in ECRS. IL-16
      production in ECRS patients is not mediated by Immunglobuline-E (IgE).

PMID- 17431660
TI  - The accuracy of the modified Evans blue dye test in detecting aspiration in head
      and neck cancer patients.
AB  - The purpose of this study was to determine sensitivity and specificity of the
      modified Evans blue dye test (MEBDT) in tracheostomised patients after treatment
      of head and neck squamous cell carcinoma (HNSCC). This was a prospective study
      with 30 consecutive patients. All individuals underwent a MEBDT and a subsequent
      fiberoptic endoscopic evaluation of swallowing (FEES) immediately after the MEBDT
      for reconsidering the validity of the MEBDT. Aspiration was present in 20
      patients documented by MEBDT and FEES. One patient was judged to aspirate by FEES
      but not by MEBDT (1 false-negative result). Nine patients showed no aspiration
      either by MEBDT or by FEES. The sensitivity of the MEBDT protocol in predicting
      aspiration among individuals in our cohort was 95.24%, the specificity 100%,
      respectively. The results of the current investigation suggest that the MEBDT is
      much more sensitive in tracheostomised HNSCC patients than in tracheostomised
      neurological patients. The MEBDT for tracheostomised HNSCC patients offers a
      quick and reliable method to identify aspiration risk in cases of severe
      dysphagia.

PMID- 17431661
TI  - Papillary thyroid microcarcinoma: incidence and prognostic factors.
AB  - The objective of this study was to define the prognostic factors of papillary
      microcarcinoma of the thyroid (PMCT), and to analyse their epidemiologic and
      histopathologic characteristics. Our series included 57 patients diagnosed with
      PMCT between 1994 and 2003 among 944 patients who underwent thyroid surgery. All
      the surgical specimens were examined in the same department of pathology using
      the same technique. The prognostic factors were elaborated from the results of
      the histological examination. The epidemiological and histopathological
      characteristics were also evaluated. Two sub-groups were distinguished: patients
      with node disease and/or with metastasis (17 patients) and patients without node
      disease and metastasis (40 patients). The architecture of PMCT was papillary in
      14% of cases, follicular in 35% of cases and mixed in 49% of cases, with no
      significant difference between any two groups. Histopathologic characteristics
      such as the vascular extension, infiltration into the adjacent parenchyma or in
      the thyroid capsule are all indicative of a poor prognosis. Two categories of
      PMCT, with and without the risk of metastatic spread, can be identified from
      these prognostic factors.

PMID- 17431662
TI  - Laryngeal plasmacytoma presenting as amyloid tumour: a case report.
AB  - Laryngeal amyloidosis can be secondary to an underlying lymphoid neoplastic
      process and in view of this concept; the cases of localized laryngeal amyloidosis
      should be carefully examined and investigated for the presence of a lymphomatous
      process. The study design is case report. We report the case of a 64-year-old man
      with progressive hoarseness. A biopsy showed histological findings consistent
      with an extramedullary plasmacytoma associated with localized amyloidosis
      involving the right hemilarynx (ventricular band, arytenoids and true cord).
      Immunohistochemical studies showed that the tumour cells of the plasmacytoma were
      monoclonal (lambda-restricted). PCR analysis of the IgH gene demonstrated a
      clonal band confirming B-cell clonality. The amyloid deposits were also shown to
      be reactive with lambda immunoglobulin light chain, suggesting the pathogenetic
      relationship between the plasmacytoma and amyloid deposition in the larynx. There
      was no other evidence of malignancy or amyloidosis elsewhere. The majority of the
      cases reported of amyloid deposition with plasmacytoma, the lesions were found in
      the nasopharynx, in contrast to our case in which the lesions were sited in the
      larynx and with the peculiarity of being multiples. Moreover, amyloid and
      plasmacytoma were clearly delimitated and the amyloid tissue was more extensive
      than the tumour tissue. This case supports the concept that localized laryngeal
      amyloidosis may be a manifestation of low-grade B-cell neoplasms.

PMID- 17431663
TI  - Intraocular surgery under systemic interferon-alpha therapy in ocular
      Adamantiades-Behcet's disease.
AB  - BACKGROUND: Adamantiades-Behcet's disease (ABD) is a multi-system disorder with
      recurrent oral and/or genital ulcerations, skin lesions and ocular involvement.
      Eye involvement is a common manifestation that affects the patients' quality of
      life more than any other. Left untreated, it leads to blindness and often to loss
      of the eye through secondary complications like phthisis or painful glaucoma. In
      some cases, such as tractional retinal detachment, secondary glaucoma or
      secondary cataract formation, intraocular surgery is required. METHODS: A
      prospective study of patients with ocular ABD who underwent intraocular surgery
      under systemic treatment with interferon-alpha was conducted. From 1999 to 2005,
      we treated eight eyes from five patients with pars plana vitrectomy (n = 1),
      phacoemulsification (n = 6) and trabeculectomy (n = 1). The mean follow-up was 49
      months (range 5-94 months). RESULTS: Seven out of eight eyes had better visual
      acuity following surgery. One eye did not benefit from cataract surgery because
      of optic nerve atrophy. Only one eye showed prolonged inflammation following
      phacoemulsification. None of the patients showed a recurrence during follow-up.
      The failure of conservative glaucoma treatment necessitated trabeculectomy in one
      eye; the patient has had no further recurrence for 6 years under monotherapy with
      interferon-alpha. CONCLUSION: Interferon-alpha is a potent therapy for
      Adamantiades-Behcet's disease with ocular involvement. It also provides a basis
      for safe and reliable surgical interventions. In seven of eight eyes, there was
      no intra- or peri-operative recurrence of inflammation, which is a common
      complication after these procedures. Only one eye showed acute and prolonged
      inflammation following cataract surgery.

PMID- 17431664
TI  - Effects of spinal recurrent inhibition on motoneuron short-term synchronization.
AB  - Spinal recurrent inhibition linking skeleto- motoneurons (alpha-MNs) via Renshaw
      cells (RCs) has been variously proposed to increase or decrease tendencies toward
      synchronous discharges between alpha-MNs. This controversy is not easy to settle
      experimentally in animal or human paradigms because RCs receive, in addition to
      excitatory input from alpha-MNs, many other modulating influences which may
      change their mode of operation. Computer simulations help to artificially isolate
      the recurrent inhibitory circuit and thus to study its effects on alpha-MN
      synchronization under conditions not achievable in natural experiments. We
      present here such a study which was designed to specifically test the following
      hypothesis. Since many alpha-MNs excite any particular Renshaw cell, which in
      turn inhibits many alpha-MNs, this convergence-divergence pattern establishes a
      random network whose random discharge patterns inject uncorrelated noise into
      alpha-MNs, and this noise counteracts any synchronization potentially arising
      from other sources, e.g., common inputs (Adam et al. in Biol Cybern 29:229-235,
      1978). We investigated the short-term synchronization of alpha-MNs with two types
      of excitatory input signals to alpha-MNs (random and sinusoidally modulated
      random patterns). The main results showed that, while recurrent inhibitory inputs
      to different alpha-MNs were indeed different, recurrent inhibition (1) exerted
      rather small effects on the modulation of alpha-MN discharge, (2) tended to
      increase the short-term synchronization of alpha-MN discharge, and (3) did not
      generate secondary peaks in alpha-MN-alpha-MN cross-correlograms associated with
      alpha-MN rhythmicity.

PMID- 17431665
TI  - Developing velocity sensitivity in a model neuron by local synaptic plasticity.
AB  - Sensor neurons, like those in the visual cortex, display specific functional
      properties, e.g., tuning for the orientation, direction and velocity of a moving
      stimulus. It is still unclear how these properties arise from the processing of
      the inputs which converge at a given cell. Specifically, little is known how such
      properties can develop by ways of synaptic plasticity. In this study we
      investigate the hypothesis that velocity sensitivity can develop at a neuron from
      different types of synaptic plasticity at different dendritic sub-structures.
      Specifically we are implementing spike-timing dependent plasticity at one
      dendritic branch and conventional long-term potentiation at another branch, both
      driven by dendritic spikes triggered by moving inputs. In the first part of the
      study, we show how velocity sensitivity can arise from such a spatially localized
      difference in the plasticity. In the second part we show how this scenario is
      augmented by the interaction between dendritic spikes and back-propagating spikes
      also at different dendritic branches. Recent theoretical (Saudargiene et al. in
      Neural Comput 16:595-626, 2004) and experimental (Froemke et al. in Nature
      434:221-225, 2005) results on spatially localized plasticity suggest that such
      processes may play a major role in determining how synapses will change depending
      on their site. The current study suggests that such mechanisms could be used to
      develop the functional specificities of a neuron.

PMID- 17431666
TI  - A small cysteine-rich extracellular protein, VCRP, is inducible by the sex
      inducer of Volvox carteri and by wounding.
AB  - The green alga Volvox carteri represents one of the simplest multicellular
      organisms: it is composed of only two cell types, somatic and reproductive.
      Volvox is capable of both vegetative and sexual reproduction. Sexual development
      of males and females is triggered by a sex-inducer at concentrations as low as
      10(-16) M. By differential screenings of cDNA libraries, a novel gene was
      identified that is under the control of this sex-inducer and that encodes a small
      cysteine-rich extracellular protein, named VCRP. Analysis of the VCRP polypeptide
      sequence suggests ten disulfide bonds and a dimetal-binding capacity. VCRP mRNA
      is detectable in males and females approximately 1 h after the spheroids' first
      contact with the sex-inducer, but transcription is restricted to the somatic cell
      type. mRNA and protein synthesis is triggered not only by the sex-inducer, but
      also by wounding. VCRP does not share significant sequence similarity with any
      known protein sequence, but a potential EGF-like calcium-binding motif and a
      potential plant metallothionein family-15 motif have been identified. The
      characteristics of VCRP suggest a function as a signal transducer molecule, an
      extracellular second messenger from somatic cells to reproductive cells, or a
      role within the stress response.

PMID- 17431667
TI  - Reactive oxygen species, ABA and nitric oxide interactions on the germination of
      warm-season C4-grasses.
AB  - Hydrogen peroxide (H(2)O(2)) as a source of reactive oxygen species (ROS)
      significantly stimulated germination of switchgrass (Panicum virgatum L.) seeds
      with an optimal concentration of 20 mM at both 25 and 35 degrees C. For non
      dormant switchgrass seeds exhibiting different levels of germination, treatment
      with H(2)O(2) resulted in rapid germination (<3 days) of all germinable seeds as
      compared to seeds placed on water. Exposure to 20 mM H(2)O(2) elicited
      simultaneous growth of the root and shoot system, resulting in more uniform
      seedling development. Seeds of big bluestem (Andropogon gerardii Vitman) and
      indiangrass [Sorghastrum nutans (L.) Nash] also responded positively to H(2)O(2)
      treatment, indicating the universality of the effect of H(2)O(2) on seed
      germination in warm-season prairie grasses. For switchgrass seeds, abscisic acid
      (ABA) and the NADPH-oxidase inhibitor, diphenyleneiodonium (DPI) at 20 microM
      retarded germination (radicle emergence), stunted root growth and partially
      inhibited NADPH-oxidase activity in seeds. H(2)O(2) reversed the inhibitory
      effects of DPI and ABA on germination and coleoptile elongation, but did not
      overcome DPI inhibition of root elongation. Treatment with H(2)O(2) appeared to
      enhance endogenous production of nitric oxide, and a scavenger of nitric oxide
      abolished the peroxide-responsive stimulation of switchgrass seed germination.
      The activities and levels of several proteins changed earlier in seeds imbibed on
      H(2)O(2) as compared to seeds maintained on water or on ABA. These data
      demonstrate that seed germination of warm-season grasses is significantly
      responsive to oxidative conditions and highlights the complex interplay between
      seed redox status, ABA, ROS and NO in this system.

PMID- 17431668
TI  - Chlamydomonas reinhardtii, a model system for functional validation of abiotic
      stress responsive genes.
AB  - Stress tolerance is a multigenic character and there are many stress responsive
      genes, which are stress specific. Although many of these have been cloned, their
      functional significance remains fragmentary. Hence it is important to identify
      the relevant stress genes involved in altering the metabolism for adaptation.
      Overexpression is one of the several approaches and Chlamydomonas is a suitable
      system to study the functional relevance of stress genes. Stress responses can
      only be assessed on prior exposure to sublethal induction stress. In this study
      the acclimation response of Chlamydomonas was assessed for different abiotic
      stresses using physiological screens like chlorophyll stability, membrane damage,
      cell viability, accumulation of free radicals, survival and recovery growth. We
      demonstrate that Chlamydomonas responds to diverse stresses and is a potential
      system to study the relevance of stress genes. The relevance of choline oxidase A
      (codA), a key enzyme in glycinebetaine biosynthesis, was examined by developing
      transformants expressing codA gene from Arthrobacter globiformis. Southern
      positive transformants showed enhanced accumulation of glycinebetaine. The
      transformants also showed enhanced growth under salinity, high light coupled with
      methylviologen-induced oxidative stress, high temperature and cold stress.
      However the transgenics were not tolerant to PEG-mediated simulated osmotic
      stress, LiCl, menadione and UV stress. Increased cell survival and decreased
      chlorophyll degradation in transformants under acclimated conditions further
      confirmed the relevance of codA in imparting stress tolerance. Our results
      indicated that the relevance of stress responsive genes can be efficiently
      validated for diverse abiotic stresses using Chlamydomonas system.

PMID- 17431669
TI  - HeOtx expression in an indirectly developing polychaete correlates with
      gastrulation by invagination.
AB  - The expression of an Otx homolog in the indirectly developing polychaete
      Hydroides elegans was characterized during embryo, trochophore, and feeding-larva
      stages. In the animal hemisphere, HeOtx is first expressed in 1q(12) blastomeres
      and their immediate descendants. Such discrete embryonic animal hemisphere Otx
      expression perhaps relates to cell-type specification functions of the larva.
      During feeding stages, transcripts are detected in adult cerebral ganglia
      precursors and putative adult eye precursors, where it may have adult brain
      regionalization functions. HeOtx is not expressed in primary trochoblast
      precursors, but it is expressed in cells adjacent to the ciliary band. HeOtx is
      also expressed in a group of cells in the dorsal midline of the early trochophore
      larva in putative posterior sensory organ precursors. The vegetal hemisphere
      expression starts in oral and lateral sides of the blastopore and later expands
      to central blastomeres that lead the gastrulation movements. During late
      gastrulation stages, the expression declines in foregut precursors, but it is
      maintained in midgut precursors, suggesting its involvement in tripartite gut
      subdivision functions. HeOtx broader and earlier endoderm expression correlates
      with gastrulation by invagination associated with the formation of the feeding
      trochophore, in contrast with a later and orally restricted Otx expression found
      in a polychaete that gastrulates by epiboly and forms a non-feeding trochophore.
      The endoderm expression and functional roles in other bilaterians suggest an
      ancestral role of Otx related to gastrulation by invagination.

PMID- 17431670
TI  - Expression and prognostic significance of Tetranectin in invasive and non
      invasive bladder cancer.
AB  - Tetranectin (TN) is a plasminogen kringle-4 binding protein that can be detected
      in the plasma and the extracellular matrix. In malignancies, TN is thought to
      enhance proteolytic processes enabling tumor cells to invade and metastasize. So
      far, TN expression has not been described in transitional cell bladder cancer
      (TCC), and there is no information on the prognostic significance of its in situ
      expression. TN expression was studied in 99 TCC patients diagnosed between 1994
      and 1997. Immunohistochemistry was performed on a tissue microarray using a
      monoclonal antibody against TN (clone 11F1). Within the mean follow-up period of
      60 months, pTa and pT2-4 TCC patients with stainable TN in the tumor stroma had a
      significant shorter recurrence-free survival and higher risk of recurrence
      compared to those without stainable TN (p = 0.0002 for both). TN expression in
      the tumor cells did not influence recurrence-free survival. In conclusion, TN is
      expressed in a subgroup of bladder cancer patients with a higher risk of
      recurrence who may take benefit from a closer follow-up.

PMID- 17431671
TI  - Predominant expression of OLIG2 over ID2 in oligodendroglial tumors.
AB  - OLIG2 is a basic helix-loop-helix transcription factor regulating the generation
      of oligodendrocytes from neural progenitor cells, and the function of OLIG2 is
      inhibited posttranslationally through the interaction with ID2. This study aims
      to examine if the analysis of OLIG2 and ID2 expression in glioma tissues helps
      the differential diagnosis of chemosensitive oligodendroglial tumors from
      astrocytic tumors. Expression levels of OLIG2 and ID2 in 11 oligodendroglial and
      27 astrocytic tumors were analyzed by reverse transcription-polymerase chain
      reaction (RT-PCR), real-time quantitative PCR, and immunohistochemistry. The mean
      expression level of OLIG2 was higher in oligodendroglial tumors than astrocytic
      tumors, but some astrocytic tumors showed high OLIG2 expression, indicating that
      OLIG2 cannot be an independent marker of oligodendroglial tumors. No significant
      difference was observed between ID2 expression in oligodendroglial tumors and
      astrocytic tumors. It was notable that OLIG2 expression was predominant over ID2
      expression in oligodendroglial tumors, while ID2 expression was predominant over
      OLIG2 expression in astrocytic tumors. Comparative genomic hybridization revealed
      that gliomas with loss on chromosome 1p, which is closely associated with
      chemosensitivity, also showed the predominant expression of OLIG2 over ID2. These
      results indicate that the immunohistochemical study on the relative expression
      level of OLIG2 to ID2 can be a useful screening for oligodendroglial tumors.

PMID- 17431672
TI  - Non-sebaceous lymphadenoma of the salivary gland: case report with
      immunohistochemical investigation.
AB  - Non-sebaceous lymphadenoma (NSL) is a rare, recently described, benign salivary
      gland tumor characterized by a dense lymphoid infiltrate and absence of sebaceous
      differentiation. To our knowledge, only seven previous cases have been reported.
      In this paper, we describe an additional example of NSL along with an extensive
      analysis of its keratin (CK) profile. The patient was a 50-year-old woman
      presenting with a slowly growing painless mass in the right parotid gland. The
      tumor was encapsulated and measured 3 x 2 x 2 cm. Microscopically, the tumor
      comprised islands of epithelial cells with centrally located duct-like structures
      within a dense lymphoid stroma. Immunohistochemically, the tumor regularly
      expressed CKs 7, 8/18, and 19, which are typical for columnar differentiation and
      CKs 17 and 5/6, which are most typically expressed in basal cells of complex
      epithelia. CK14 was only expressed in rare scattered cells and eventually in
      groups of cells. The expression of CK10/13, which correlates with squamous
      differentiation, was negative. Additionally, immunostaining for smooth muscle
      actin, vimentin, and S-100 was also performed. The immunohistochemical findings
      in the neoplastic epithelial component of our case suggest a differentiation of
      "intercalated duct phenotype" without myoepithelial cell participation.

PMID- 17431673
TI  - "Benign" metastatic meningioma: clinico-pathological analysis of one case
      metastasising to the lung and overview on the concepts of either primitive or
      metastatic meningiomas of the lung.
AB  - Lung "metastases" of benign meningiomas are rarely described events of biological
      and clinical interest. We, here, report of a 70-year-old healthy woman found by
      CT scan to have multiple lesions, the two largest in the right lung on routine
      examination. Anamnesis revealed that the patient underwent a surgical resection
      of cerebral meningioma 12 years before. The larger lung lesion was a 3-cm node
      located in the right lung and was removed by wedge resection. Macroscopically, it
      showed well-defined borders, whitish colour and firm consistency; histologically,
      it was uniformly composed by spindle meningothelial cells arranged in fascicules
      including psammoma bodies. The morphological and immunohistochemical features of
      this lesion, together with the similarity with the original cerebral tumour and
      its indolent evolution, led to a final diagnosis of "benign" meningioma
      metastatic to the lung. Lung metastatic meningiomas may be a diagnostic challenge
      because of their unusual site of presentation and the possible confusion with
      primitive lung meningiomas or primary mesenchymal lung lesions. They represent a
      typical example of "benign" tumours that may implant to the lung similar to other
      tumours, definitely considered benign but reported to rarely present unusual
      secondary localization.

PMID- 17431674
TI  - Skp2 expression is associated with down-regulation of p27 protein and cell
      proliferation in salivary adenoid cystic carcinoma.
AB  - Adenoid cystic carcinoma (ACC) is a malignant salivary gland tumor, which shows
      frequent recurrence and metastasis, ultimately with a poor outcome. We previously
      demonstrated that p27 down-regulation is frequently found and is due to an
      enhancement of its degradation in ACC. In this study, we transfected
      nondegradable p27 mutant (T187A) and wild-type gene into ACC cell line.
      Transfection of T187A mutant gene was more effective on inhibition of cell growth
      of ACC cells, suggesting that aberration of p27 degradation may be present in
      ACC. As F-box protein S-phase kinase-associated protein 2 (Skp2), which is
      necessary for ubiquitin-mediated degradation of p27, is involved in p27 down
      regulation in various cancers, we examined the Skp2 expression and its
      association with p27 expression in 50 ACC cases. We found Skp2 expression in 36%
      of ACC cases and inverse association between the expression of Skp2 and p27.
      Moreover, Skp2 small interfering ribonucleic acid (siRNA) transfection decreased
      Skp2 protein and accumulation of p27 protein and inhibited the cell growth of ACC
      cells in vitro. These findings, overall, suggest that Skp2 may play an important
      role in ACC development through the down-regulation of p27 and that Skp2 siRNA
      can be a novel modality of cancer gene therapy for suppression of p27 down
      regulation in ACC.

PMID- 17431675
TI  - Specific activation of the different fibrogenic cells in rat cultured liver
      slices mimicking in vivo situations.
AB  - Due to the loss of cell-cell and cell-matrix interactions, cell culture models
      poorly mimic the in vivo situation. Therefore, we tested the applicability of
      precision-cut liver slices (PCLS) to study the early activation of the two main
      liver fibrogenic cell subpopulations: hepatic stellate cells (HSC) and portal
      fibroblasts (PF). PCLS were treated with thioacetamide or acetaminophen to induce
      HSC activation. In PCLS culture, both were able to trigger centrolobular lesion
      and HSC activation as observed in vivo. However, thioacetamide also presented a
      toxic effect on portal tract cells. In this PCLS model of centrolobular lesion,
      the antioxidant N-acetylcysteine was able to prevent acetaminophen-induced
      injury. To induce a specific activation of PF, PCLS were treated with epidermal
      growth factor or beta-oestradiol. As in vivo, epidermal growth factor and beta
      oestradiol induced bile duct epithelial cell proliferation accompanied by PF
      activation; however, beta-oestradiol also triggers sinusoidal cell proliferation.
      We demonstrated that treatments usually used in vivo to induce liver fibrosis
      allow, in cultured PCLS, the specific activation of the two main liver fibrogenic
      cell subpopulations, making this model very useful to study the mechanisms
      involved in early fibrogenic cell activation.

PMID- 17431676
TI  - Frequency and diagnostic patterns of lymphomas in liver biopsies with respect to
      the WHO classification.
AB  - The recent World Health Organization (WHO) classification of hematopoietic and
      lymphoid tissue tumors represents the first worldwide consensus classification of
      these malignancies. However, the applicability of this classification to a
      representative number of hepatic lymphomas in liver biopsy specimens has not yet
      been investigated. The frequency and infiltration pattern of a series of 205
      liver biopsies with lymphoma manifestations was analyzed with the aid of
      immunohistochemical and molecular pathological analyses. Diffuse large B-cell
      lymphoma (DLBCL) was by far the most frequent entity, comprising 45% of the cases
      analyzed. Using a previously published immunohistochemical algorithm, 35% of 80
      DLBCL were assigned to a germinal center B-cell-like (GCB) and 65% to a non-GCB
      group. Most B-cell lymphoma entities involving the liver revealed a
      characteristic infiltration pattern. Diagnostically challenging entities were T
      cell-rich B-cell lymphomas, anaplastic large cell lymphomas and peripheral T-cell
      lymphomas, which frequently required additional molecular clonality assessment.
      Overall, the percentage of T-cell lymphomas in the liver (12%) was higher as
      compared to other extranodal sites except for the skin and the small intestine.
      This study provides relevant data on the distribution of hepatic lymphomas and
      demonstrates the applicability of the WHO classification proposing a diagnostic
      algorithm for liver biopsies.

PMID- 17431678
TI  - Arginine-vasopressin as a rescue therapy in children and neonates for
      catecholamine-resistant shock.

PMID- 17431677
TI  - The threat of avian influenza A (H5N1). Part III: Antiviral therapy.
AB  - Among emerging and re-emerging infectious diseases, influenza constitutes one of
      the major threats to mankind. In this review series epidemiologic, virologic and
      pathologic concerns raised by infections of humans with avian influenza virus
      A/H5N1 as well as treatment options are discussed. The third part discusses
      therapeutic options. Neuraminidase (NA) inhibitors are the most promising agents
      despite uncertainty about efficacy. Dosage increase, prolonged treatment or
      combination therapies may increase treatment efficacy and/or inhibit resistance
      formation. Immune system dysregulation contributes to H5N1 disease. Although
      current evidence does not support the use of anti-inflammatory drugs beneficial
      effects cannot be excluded at later disease stages.

PMID- 17431679
TI  - Torticollis is a usual symptom in posterior fossa tumors.

PMID- 17431680
TI  - Eimeria bovis infection enhances adhesion of peripheral blood mononuclear cells
      to and their transmigration through an infected bovine endothelial cell monolayer
      in vitro.
AB  - The first schizogony of Eimeria bovis takes place in lymphatic endothelial cells
      of the ileum, resulting in the formation of macroschizonts within 2-3 weeks. In
      this study, we analyse early cellular immune responses to infected host cells on
      the basis of peripheral blood mononuclear cell (PBMC) adhesion on and
      transmigration through infected bovine umbilical vein endothelial cell (BUVEC)
      monolayers. Adhesion of PBMC was upregulated by an E. bovis infection. Most
      marked effects were observed 1 day p.i.; thereafter, PBMC adhesion declined
      reaching control levels from day 8 p.i. onward. CD8(+) T cells adhered more
      frequently to infected BUVEC (42%) than CD4(+) T cells (25%). About one third of
      attached PBMC were represented by gammadelta-TCR(+) T cells. Adhesion of T cells
      was not restricted to parasitised host cells, but occurred almost equally on non
      infected BUVEC within the same monolayer. Furthermore, we found moderately
      enhanced levels of PBMC transmigration through infected BUVEC monolayers, in
      particular on day 2 p.i. The data presented here suggest that E. bovis infection
      of BUVEC induces endothelial cell-derived proinflammatory reactions, which appear
      suitable for the initiation of both adaptive and innate immune responses.

PMID- 17431681
TI  - A novel genetic locus for juvenile myoclonic epilepsy at chromosome 5q12-q14.
AB  - Juvenile myoclonic epilepsy is a clinically well-defined, age-related common
      idiopathic generalized epilepsy syndrome with substantial genetic basis to its
      etiology. We report identification of a novel epilepsy locus at chromosome 5q12
      q14 in a family exhibiting autosomal dominant form of juvenile myoclonic epilepsy
      from south India. The highest two-point LOD score of 3.3344 was obtained for the
      microsatellite markers D5S641 and D5S459 at 5q14. Centromeric and telomeric
      chromosomal boundaries of the locus were defined by D5S624 and D5S428,
      respectively. The 5q12-q14 locus encompasses about 25 megabases of the genomic
      region and harbours several candidate genes. Further work involving a detailed
      mutational analysis of the locus, to isolate the gene responsible for the
      epilepsy disorder in the family, shall help enhance our understanding of
      molecular basis of epilepsy disorders.

PMID- 17431684
TI  - Effects of resource level and habitat type on behavioral and morphological
      plasticity in Eurasian perch.
AB  - Spatial and temporal heterogeneity in the environment is a common feature
      affecting many natural populations. For example, both the resource levels and
      optimal habitat choices of individuals likely change over time. One way for
      organisms to cope with environmental variation is to display adaptive plasticity
      in traits such as behavior and morphology. Since trait plasticity is hypothesized
      to be a prerequisite for character divergence, studies of mechanisms behind such
      plasticity are warranted. In this study, we looked at the interaction of two
      potentially important environmental variables on behavioral and morphological
      plasticity in Eurasian perch (Perca fluviatilis L.). More specifically, the
      plastic responses in activity and morphology of perch exposed to different
      resource levels and simulated habitat types were studied in an aquarium
      experiment. The resource level experienced had a large influence on plasticity in
      both activity and morphology. Behavioral adaptations have been thought to mediate
      morphological transitions, and we suggest that the morphological response to the
      resource level was mediated by differences in activity and growth rates. The
      habitat type also affected morphological plasticity but to a lesser extent, and
      there was no effect on activity from habitat type. Based on these results, we
      suggest that it is essential to include several environmental factors acting in
      concert when studying mechanisms behind trait plasticity. We also propose that
      variation in resource levels might play a key role in fostering trait plasticity
      in at least fish populations, while other environmental variables such as
      divergent habitat complexities and prey types might be less influential. Dynamics
      in resource levels and optimal habitat choices might thus be important factors
      influencing character divergence in natural populations.

PMID- 17431685
TI  - [Classification of headache disorders].
AB  - In 2003 the International Headache Society (IHS) published the second edition of
      the International Classification of Headache Disorders. Diagnostic criteria for
      no less than 206 separate headache diagnoses are presented in the parts (I)
      primary headaches, (II) secondary headaches and (III) cranial neuralgia, central
      and primary facial pain. The headaches are classified according to the etiology
      in case of the secondary headaches and according to the phenomenology in case of
      the primary headaches. It is the task of the headache specialist to identify the
      correct headache diagnose with the smallest effort possible. Both, the
      differentiation between secondary and primary headaches and the differentiation
      between the various primary headaches are of equal importance.

PMID- 17431682
TI  - Linkage and association analysis of candidate genes for TB and TNFalpha cytokine
      expression: evidence for association with IFNGR1, IL-10, and TNF receptor 1
      genes.
AB  - Tuberculosis (TB) is a growing public health threat globally and several studies
      suggest a role of host genetic susceptibility in increased TB risk. As part of a
      household contact study in Kampala, Uganda, we have taken a unique approach to
      the study of genetic susceptibility to TB by developing an intermediate phenotype
      model for TB susceptibility, analyzing levels of tumor necrosis factor-alpha
      (TNFalpha) in response to culture filtrate as the phenotype. In the present
      study, we analyzed candidate genes related to TNFalpha regulation and found that
      interleukin (IL)-10, interferon-gamma receptor 1 (IFNGR1), and TNFalpha receptor
      1 (TNFR1) genes were linked and associated to both TB and TNFalpha. We also show
      that these associations are with progression to active disease and not
      susceptibility to latent infection. This is the first report of an association
      between TB and TNFR1 in a human population and our findings for IL-10 and IFNGR1
      replicate previous findings. By observing pleiotropic effects on both phenotypes,
      we show construct validity of our intermediate phenotype model, which enables the
      characterization of the role of these genetic polymorphisms on TB pathogenesis.
      This study further illustrates the utility of such a model for disentangling
      complex traits.

PMID- 17431686
TI  - [Psychological treatment of chronic headache and facial pain].
AB  - Chronic headache and facial pain cannot be categorized as purely organic or
      purely psychological; therefore, treatment should be both medical and
      psychotherapeutic. An interdisciplinary approach optimises treatment results and
      significantly reduces the intensity and frequency of the pain. This article
      illustrates a cognitive behavioural treatment strategy that has shown a clear
      reduction in patient impairment. With extensive education and training in pain
      management techniques, patients are enabled to exert influence over their pain,
      preventing and easing it and dealing with it strategically. The results are
      improved self-control, improved quality of life, and a possible reduction in the
      consumption of pain-killing drugs.

PMID- 17431687
TI  - Sources of strength perceived by females caring for relatives diagnosed with
      cancer: an exploratory study from India.
AB  - GOALS OF WORK: The aim of the study was to explore sources of strength in the
      process of caregiving from the perspectives of Indian women caring for relatives
      suffering from cancer. In addition, it aimed at exploring self-reported
      occurrence of positive moments and personal changes experienced during the care
      giving process. MATERIALS AND METHODS: Twenty female caregivers participated in
      two to four interview sessions. The average caregiver was about 40 years old.
      Spouses and children as caregivers had the highest representation in the sample.
      The care recipients had heterogeneous cancer diagnoses and were undergoing active
      treatment. MAIN RESULTS: Religious beliefs and practices and positive appraisal
      of the caregiver role in terms of "value" emerged as the most frequently cited
      intrapersonal sources of strengths. Religious beliefs and practices were linked
      with positive appraisals of care-giving demands and experience of hope. The
      participants also described several interpersonal sources of strengths, e.g.,
      family, medical fraternity, and care recipients themselves. The narratives of the
      participants indicated the occurrence of positive moments as well as perceptions
      of positive personal changes during the care-giving process. CONCLUSIONS: The
      findings have implications for further research on positive aspects of caregiving
      as well as for development of intervention components that may help caregivers
      maintain and enhance their well-being.

PMID- 17431688
TI  - What symptom and functional dimensions can be predictors for global ratings of
      overall quality of life in lung cancer patients?
AB  - PURPOSE: This study explores what dimensions of a health-related quality of life
      (HRQOL) questionnaire predict global ratings of overall quality of life (QOL) in
      lung cancer patients in assessments by patients and significant others,
      respectively. MATERIAL AND METHODS: The analyses were based on dyadic assessments
      from lung cancer patients and their significant others. A subset of scales and
      items from the Swedish version of the European Organization for Research and
      Treatment of Cancer (EORTC) QLQ C30 and the lung-cancer-specific module, LC-13,
      was selected. Using multiple regression procedures, the relative importance of
      different symptoms and of functional impairments in predicting overall QOL was
      examined. RESULTS: The multiple regressions revealed that emotional functioning
      and fatigue were the only significant predictors of overall QOL for both the
      patients and the significant others' assessments. In addition, physical
      functioning was found to be another predictor in the significant others'
      assessments. CONCLUSION: The results emphasize that it is essential to consider
      both emotional functioning and fatigue as important areas for overall QOL in lung
      cancer patients.

PMID- 17431689
TI  - Correlation between variation in quality of life and change in hemoglobin level
      after treatment with epoetin alfa 40,000 IU administered once-weekly.
AB  - INTRODUCTION: Anemia is frequently associated with cancer due to the disease
      itself and antineoplastic treatments. This open-label, uncontrolled, multi-center
      study evaluated the effects of once-weekly (qw) epoetin alfa 40,000 IU on
      hemoglobin (Hb) levels and quality of life (QoL) in anemic patients receiving
      chemotherapy for solid tumors. MATERIALS AND METHODS: A total of 522 patients
      with Hb level < or =12 g/dL received epoetin alfa 40,000 IU qw subcutaneously for
      9-20 weeks to reach and maintain Hb range of 12-14 g/dL. QoL was assessed with
      the Functional Assessment of Cancer Therapy-Anemia (FACT-An [anemia sub-scale])
      and Cancer Linear Analogue Scale (CLAS) at study entry, after two chemotherapy
      cycles, and at study end. RESULTS: Mean baseline Hb was 10.43 g/dL. Hb increases
      (g/dL) from baseline after 4, 8, 12 weeks and at study end were 1.07, 1.77, 1.92
      and 1.71 g/dL, respectively. Response rates (Hb increase > or =1 and > or =2 g/dL
      during trial) were 81% and 61%, respectively. Mean increases in the FACT-An score
      from baseline (mean 55.4) were 3.1 after two chemotherapy cycles and 3.3 at study
      end; mean increases in the CLAS score from baseline (58.4 mm) were 5.9 mm after
      two chemotherapy cycles and 6.5 mm at study end. DISCUSSION: The greatest QoL
      increase was recorded when patients approached Hb level of 12 g/dL, independent
      of the baseline Hb level. Hb changes from baseline to trial end were related to
      corresponding changes in the FACT-An score. A positive correlation was also
      observed in patients with progressive disease. Adverse events were essentially
      those associated with chemotherapy. Incidence of thrombovascular events (6.7%)
      did not differ from the expected standard treatment in cancer patients. Epoetin
      alfa 40,000 IU qw increased Hb levels and improved or preserved QoL.

PMID- 17431690
TI  - Ways to obtain a breast cancer diagnosis, consistency of information, patient
      satisfaction, and the presence of relatives.
AB  - GOALS OF WORK: What physicians told breast cancer patients about their diagnosis,
      who informed them, and how this information was conveyed were examined in this
      study. Finally, the relatives' role in this communication process was considered.
      MATERIALS AND METHODS: Women with primary breast cancer (N = 222) below the age
      of 70 were interviewed after surgery and after they were informed about their
      diagnosis. MAIN RESULTS: One hundred twenty-one women consulted their primary
      gynecologist first, then they were referred to a radiologist, and finally to the
      secondary care gynecologist. Forty-seven women omitted the radiologist and only
      five went directly to the hospital for treatment. In most cases (N = 199), the
      general practitioner was not involved. Receiving inconsistent information was
      associated with patient dissatisfaction. This also applies to women who received
      their diagnosis on the phone. Women awaiting a worse diagnosis were more likely
      to be accompanied by another person. CONCLUSIONS: Future studies should focus on
      the possible involvement of family doctors and relatives during the diagnostic
      process. Giving inconsistent information should be avoided.

PMID- 17431691
TI  - The diverse and pervasive chemistries of the alpha-keto acid dependent enzymes.
AB  - The number of identified and confirmed alpha-keto acid dependent oxygenases is
      increasing rapidly. All of these enzymes have a relatively simple liganding
      arrangement for a single ferrous ion but collectively conduct a highly diverse
      set of chemistries. While hydroxylations and a variety of oxidation reactions
      have been most commonly observed, new reactions involving dealkylations,
      epimerizations and halogenations have recently been discovered. In this
      minireview we present what is known of the alpha-keto acid dependent enzymes and
      offer an argument that the chemistry that is unique to each enzyme occurs only
      after the production of a pivotal ferryl-oxo intermediate.

PMID- 17431692
TI  - An international multicenter study on the effectiveness of a denture adhesive in
      maxillary dentures using disposable gnathometers.
AB  - No consensus has been achieved on whether denture adhesives are beneficial
      adjuncts in denture-wearers management. The purpose of this international
      multicenter study was to determine objectively the effect of a denture adhesive
      (Kukident) on the retention of complete maxillary dentures using disposable
      gnathometers. The disposable gnathometers have a decimal scale for measuring the
      incisal force before dislodgement (= maximum incisal force) of maxillary
      dentures. The intra-observer reliability, the inter-observer reliability, and the
      linearity of the gnathometer units of the disposable gnathometers were examined
      in three pilot studies. Participants of the international multicentre main study
      were 88 patients who had been selected for complete maxillary denture treatment.
      The maximum incisal force of their previous and new denture without and with
      adhesive was measured using disposable gnathometers. The intra- and inter
      observer reliability of the disposable gnathometers was very good, and there was
      a linear relation between the gnathometer units. The effect of the denture
      adhesive on the maximum incisal force of complete maxillary dentures was
      statistically significant in previous as well as new dentures, being more
      pronounced in previous than in new dentures.

PMID- 17431693
TI  - Necessity of surgical dental foci treatment prior to organ transplantation and
      heart valve replacement.
AB  - Diagnosis and surgical treatment of septic foci (e.g., apical or marginal and
      profound periodontitis, cysts, unrestorable teeth, or abscesses) in patients
      awaiting organ transplants and heart valve replacement (HVR) have become a
      recommended, yet controversial standard procedure. This study aims to evaluate
      the numerical extent of the required oral surgical procedures removing septic
      foci in these patients. Data of 204 patients (115 males/89 females) of the
      Department of Oral- and Maxillofacial Surgery with an average age of 58 years
      were evaluated in terms of necessary oral surgical procedures before HVR or
      kidney (K), heart (H), or liver (L) transplant (T) and were compared with data
      from patients not undergoing transplantation or HVR, who were referred for other
      reasons such as oral surgery. The number of tooth extractions or apicoectomies
      per patient averaged two to five for each of the four patient groups (KT, 0-7
      affected teeth; HT, 0-5; LT, 1-5; and HVR, 1-10). Treatment of periodontitis was
      necessary in 64% of patients. A total of 70% of patients required oral surgical
      procedures before HT, LT, and HVR, while 84% needed before KT. Removal of oral
      septic foci is necessary to avoid jeopardizing the success of transplantations.
      With regard to the surprisingly high need for surgical treatment in this patient
      population, assessment of these patients by the appropriate specialist and
      continuation with a follow-up program is still highly recommended.

PMID- 17431694
TI  - Prevalence and predictive features of bacteremic urinary tract infection in
      emergency department patients.
AB  - The aim of this study was to determine the prevalence and predictive features of
      bacteremia among patients evaluated in the emergency department for urinary tract
      infection. Of the 350 patients with symptomatic urinary tract infection included
      in this retrospective study, 53 (15%; 95%CI 11.6-19.4%) were bacteremic. Five
      variables were independently associated with bacteremia: residence at home rather
      than in an institution (OR 4; 95%CI 1.5-10.7), presence of an indwelling urinary
      catheter (OR 3.3; 95%CI 1.3-8.8), presence of band forms in the blood count (OR
      3.3; 95%CI 1.5-7.2), shaking chills (OR 2.3; 95%CI 1.1-4.8), and neutrophilia (OR
      1.1; 95%CI 1.04-1.15). These easily assessable parameters may assist in the
      diagnosis of bacteremic urinary tract infection and the selection of empiric
      antibiotic treatment, thus potentially improving a patient's prognosis.

PMID- 17431695
TI  - Gas in the kidney: CT findings.
AB  - Gas in the renal parenchyma is a rare finding seen best with computed tomography
      (CT). It can be encountered in a wide range of clinical conditions, some of them
      life-threatening like emphysematous pyelonephritis, whereas in others, it may
      represent a postoperative or procedure outcome. The latter are not usually a
      clinical emergency (for example, after nephrostomy insertion or in a urinary
      intestinal connection). Due to the increasing use of abdominal CT examinations,
      radiologists, especially in emergency setting, should be aware of this rare
      finding and be familiar with its differential diagnosis.

PMID- 17431696
TI  - Multilevel finite element modeling for the prediction of local cellular
      deformation in bone.
AB  - The underlying mechanisms by which bone cells respond to mechanical stimuli or
      how mechanical loads act on osteocytes housed in lacunae in bone are not well
      understood. In this study, a multilevel finite element (FE) approach is applied
      to predict local cell deformations in bone tissue. The local structure of the
      matrix dictates the local mechanical environment of an osteocyte. Cell
      deformations are predicted from detailed linear FE analysis of the
      microstructure, consisting of an arrangement of cells embedded in bone matrix
      material. This work has related the loads applied to a whole femur during the
      stance phase of the gait cycle to the strain of a single lacuna and of
      canaliculi. The predicted bone matrix strains around osteocyte lacunae and
      canaliculi were nonuniform and differed significantly from the macroscopically
      measured strains. Peak stresses and strains in the walls of the lacuna were up to
      six times those in the bulk extracellular matrix. Significant strain
      concentrations were observed at sites where the process meets the cell body.

PMID- 17431697
TI  - Patient literacy and question-asking behavior during the medical encounter: a
      mixed-methods analysis.
AB  - BACKGROUND: Although patient participation in the medical encounter confers
      significant benefits, many patients are reluctant to ask questions of their
      physicians. Patients' literacy level may affect their level of participation and
      question-asking behaviors. OBJECTIVE: To examine the effect of literacy on the
      number and types of questions asked by patients during primary care office
      visits. DESIGN: Convenience sample recruited between April and November 2004.
      Physician-patient visits were audiotaped, and patient questions from complete
      encounters (N = 57) were coded using an adaptation of the Roter Interaction
      Analysis System. PATIENTS: Participants were predominantly middle-aged (mean age
      = 56.7 years), female (75.4%), and African American (94.7%). Low literacy skills
      (< or = 6th grade reading level) were present in 38.6%. MEASUREMENTS: We
      hypothesized prospectively that low-literacy patients would ask fewer total
      questions and fewer questions about key aspects of their medical care. RESULTS:
      Low-literacy adults asked significantly fewer questions about medical care issues
      (median = 4 vs 6 among patients with higher literacy levels, p = .014). They also
      tended to ask fewer questions overall (median = 7 vs 10, p = .070). Low-literacy
      patients were more likely to ask the physician to repeat something (p = .013),
      indicating an initial lack of understanding. They were less likely to use medical
      terminology, refer to medications by name, request additional services, or seek
      new information. Question-asking behavior was not significantly related to
      patient gender, age, years of education, or physician-patient gender concordance.
      CONCLUSIONS: Literacy level appears to be an important determinant of patients'
      participation in the medical encounter. Low-literacy patients ask fewer questions
      about their medical care, and this may affect their ability to learn about their
      medical conditions and treatments.

PMID- 17431698
TI  - The effects of primary care physician visit continuity on patients' experiences
      with care.
AB  - BACKGROUND: Visit continuity is important to patients and valued by physicians.
      However, it is virtually impossible for primary care physicians (PCPs) to provide
      care during every paneled patient visit. It remains unclear whether PCP visit
      discontinuity can be planned in a way that is least disruptive to patients'
      experiences with care. OBJECTIVE: This study aims to clarify whether visit
      continuity affects patients' experiences with primary care equally for all
      patients. DESIGN: From January 2004 through March 2005, a large multispecialty
      practice in Massachusetts administered the Ambulatory Care Experience Survey
      (ACES) monthly to a random sample of patients visiting each of 145 PCPs. The
      analytic sample includes 14,835 patients with 2 or more primary care visits over
      the 6 months before being surveyed. Usual Provider Continuity (UPC), an
      administratively based measure of PCP visit continuity, was calculated for all
      respondents. Multilevel regression models that accounted for the clustering of
      patients within physicians modeled the relationship between UPC and each ACES
      measure. Interaction effects between UPC and gender, education, self-rated
      health, and PCP-patient relationship duration were tested. RESULTS: Physician
      patient interaction quality, including physician communication, knowledge of the
      patient, health promotion support, and organizational access were more strongly
      influenced by visit continuity among respondents in early stages of a PCP-patient
      relationship (P < 0.01) and with worse self-rated health (P < 0.01). CONCLUSIONS:
      Improvements in physician-patient relationship quality can be achieved by
      targeting visit continuity improvement efforts to patients who benefit most,
      particularly those in early stages of a PCP-patient relationship and/or perceive
      their health as poor.

PMID- 17431699
TI  - Global gene expression analysis in fetal mouse ovaries with and without meiosis
      and comparison of selected genes with meiosis in the testis.
AB  - In order to identify novel genes involved in early meiosis and early ovarian
      development in the mouse, we used microarray technology to compare
      transcriptional activity in ovaries without meiotic germ cells at embryonic age
      11.5 (E11.5) and E13.5 ovaries with meiosis. Overall, 182 genes were
      differentially expressed; 134 were known genes and 48 were functionally
      uncharacterized. A comparison of our data with the literature associated, for the
      first time, at least eight of the known genes with female meiosis/germ cell
      differentiation (Aldh1a1, C2pa, Tex12, Stk31, Lig3, Id4, Recql, Piwil2). These
      genes had previously only been described in spermatogenesis. The microarray also
      detected an abundance of vesicle-related genes of which four were upregulated
      (Syngr2, Stxbp1, Ric-8, SytIX) and one (Myo1c) was downregulated in E13.5
      ovaries. Detailed analysis showed that the temporal expression of SytIX also
      coincided with the first meiotic wave in the pubertal testis. This is the first
      time that SytIX has been reported in non-neuronal tissue. Finally, we examined
      the expression of one of the uncharacterized genes and found it to be gonad
      specific in adulthood. We named this novel transcript "Gonad-expressed transcript
      1" (Get-1). In situ hybridization showed that Get-1 was expressed in meiotic germ
      cells in both fetal ovaries and mature testis. Get-1 is therefore a novel gene in
      both male and female meiosis.

PMID- 17431700
TI  - Brain metabolites in definite amyotrophic lateral sclerosis. A longitudinal
      proton magnetic resonance spectroscopy study.
AB  - Biomarkers beyond clinical assessment are needed in patients who suffer from
      amyotrophic lateral sclerosis (ALS). Here, single-voxel proton magnetic resonance
      spectroscopy ((1)H MRS) of the gray matter of the motor cortex and the white
      matter including the pyramidal tracts was used to investigate concentrations of N
      acetylaspartate (NAA), creatine (Cr), choline (Cho), myoinositol, glutamate, and
      glutamine in patients with definite ALS in a longitudinal design (three
      measurements at study inclusion, after 3 and 6 months). A volume-corrected
      analysis of gray and white matter fractions within the volumes of interest (VOI)
      was performed for the identification of the absolute metabolite concentrations.
      The patient group showed a significant decline of the compound NAA over time in
      the motor cortex areas both of the clinically more and less affected hemisphere
      between first measurement and month 6 and for the less affected side additionally
      between first measurement and month 3. For the NAA/(Cr + Cho) ratio, significant
      decline in the less affected hemisphere was observed from the first measurement
      to month 3 and to month 6 as well as from month 3 to month 6. In contrast,
      neither NAA nor the NAA/(Cr + Cho) ratios in the white matter areas showed any
      significant alterations. All other compounds showed no significant changes over
      time. In summary, the longitudinal changes of cortical metabolite concentrations
      in the course of ALS could be assessed by optimized (1)H MRS techniques at group
      level, so that (1)H MRS parameters, in particular volume-corrected values of NAA
      in the clinically less affected hemisphere, seem to have the potential to serve
      as a surrogate marker for monitoring ALS disease progression.

PMID- 17431702
TI  - Albumin therapy in acute stroke patients.
AB  - Preclinical studies have recently shown that albumin has neuroprotective effects
      for stroke in animal models. Thus, we sought to evaluate the effects of albumin
      therapy in patients with acute cerebral infarcts. We prospectively studied 49
      patients with moderate-to-severe cerebral infarcts within the middle cerebral
      arterial territory into one of two groups: the control group (N = 18) received
      saline, whereas the albumin group (N = 31) received either 40 g or 80 g of
      albumin within 24 h from symptom onset. The modified National Institutes of
      Health Stroke Scale (mNIHSS) and diffusion-weighted imaging (DWI) were serially
      checked. There was no adverse effect related to albumin therapy. Although there
      was no significant difference in both baseline mNIHSS score and DWI lesion volume
      on admission, the mNIHSS scores at the 14(th) day after treatment and the
      increase in DWI lesion volume 72-96 h after treatment were significantly reduced
      in patients of the albumin group (p = 0.001 and 0.012, respectively); these
      effects were dose- and time- related. The outcome on the 90(th) day after stroke
      onset was more favorable in the albumin group than in the control group. Within
      the albumin group, patients who had patent or recanalized vessels showed more
      significant improvement than patient without recanalization (p = 0.046). Our
      results indicate that albumin therapy is a safe and effective modality in
      patients with acute cerebral infarction. This study also suggests that the
      effects of albumin therapy may vary depending on vessel status of the patient.

PMID- 17431701
TI  - The amplitude of lower leg motor evoked potentials is a reliable measure when
      controlled for torque and motor task.
AB  - OBJECTIVES: Motor evoked potential (MEP) amplitudes have the disadvantage of a
      high variability when repeatedly assessed. This affects the reliability of MEP
      amplitude measurements taken during the course of motor incomplete spinal cord
      injury (iSCI). The study investigated the reliability of anterior tibial (TA) MEP
      measures controlled for dorsal flexion torque and motor task. METHODS: TA MEPs
      were recorded at 10, 20, 40 and 60% of maximal voluntary contraction (MVC) during
      a static and dynamic (isometric increase of dorsal flexion torque) motor task. To
      determine reliability, 20 healthy and five chronic iSCI subjects were tested
      twice (> or =7 days) by the same investigator. Intraclass correlation
      coefficients (ICCs) were calculated. MEP amplitudes and latencies were compared
      between 20 healthy and 29 iSCI subjects. RESULTS: The reliability of MEP
      amplitude was in general good (ICC > or = 0.52) and was highest during the static
      task at 40% MVC (ICC = 0.77). The increased facilitation by the dynamic motor
      task showed the best reliability at 20% MVC (ICC = 0.48). The reliability was
      good to excellent for MEP latency (0.46 < or = ICC < or = 0.81), MVC (ICC > or =
      0.90) and for the TMS threshold required to evoke a MEP response (ICC > or =
      0.77). The torque generated by the MEP response ()0.02 < or = ICC < or = 0.55)
      and the duration of the silent period (0.07 < or = ICC < or = 0.50) were not
      reliable. Both MEP amplitudes and latencies differed significantly between
      healthy and iSCI subjects. CONCLUSIONS: Controlling for torque generation and
      motor task establishes a reliability of TA MEP amplitudes that is sufficient for
      longitudinal assessments in motor incomplete SCI.

PMID- 17431703
TI  - Post-deep brain stimulation--gradual non-stimulation dependent decrease in
      strength with attenuation of multiple sclerosis tremor.
AB  - Tremor in multiple sclerosis is considered to be a persistent and progressive
      sign. We describe five patients with multiple sclerosis in whom upper limb tremor
      severity gradually decreased over a period of several years after deep brain
      stimulation. In every case this attenuation of tremor was accompanied by
      increasing pyramidal weakness in the relevant upper limb. In two patients this
      attenuation of tremor remained after stimulation was permanently switched off. In
      one other patient, where upper limb strength remained normal, tremor severity
      gradually worsened in spite of continuing stimulation. There was a highly
      significant difference (p = 0.0007) between the changes in intention tremor
      severities when the arms with increasing pyramidal weakness (n = 9) were compared
      to those in which normal strength was retained throughout follow-up period (n =
      3); intention tremor decreased in the former and increased in the latter by means
      of -3.66 and +4.0 points of a 0-10 tremor scale respectively. There was also a
      significant correlation (0.699; p = 0.0359) between decreasing upper limb
      strength and decreasing intention tremor severity for the upper limbs of patients
      that had undergone contralateral DBS.

PMID- 17431704
TI  - Investigation of TGFB2 as a candidate gene in multiple sclerosis and Parkinson's
      disease.
AB  - Given the known roles of TGFbeta2 in both regulating the immune system and
      promoting the survival of dopaminergic neurons, it is feasible that genetic
      variations in TGFB2 might play an aetiological role in neurological diseases such
      as Multiple Sclerosis (MS) and Parkinson's disease (PD). Hence we performed an
      indirect association analysis of TGFB2 using 8 haplotype-tagging SNPs in a
      population of 937 MS patients, 538 PD cases and 2022 controls. We found no
      evidence for association with susceptibility or progression of MS, but have
      demonstrated a trend towards association of the 5' region of the gene with
      susceptibility to PD. Further analysis of TGFB2 is warranted in other PD cohorts.

PMID- 17431705
TI  - ALS multidisciplinary clinic and survival. Results from a population-based study
      in Southern Italy.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease
      affecting motorneurons, for which there is no effective cure. Because of the
      multifactorial nature of impairment and disablity in ALS, multidisciplinary
      clinics (MDC) have been recently introduced in the management of ALS patients;
      their effects on survival remain, however, largely debated. OBJECTIVE: To compare
      survival of ALS patients who received their care at MDC with that of patients
      followed by general neurology clinics. METHODS: Source of the study was a
      prospective population-based registry of ALS established in Puglia, Southern
      Italy, in 1997. We examined survival of 126 out of 130 incident ALS cases that
      were diagnosed during the period 1998-99. RESULTS: 84 patients (67%) were
      enrolled and followed by MDC and the remaining 42 (33%) by general neurological
      clinics. No difference in median survival time from the diagnosis was observed
      between patients followed by ALS multidisciplinary (17.6 months) and general
      clinics (18 months). No beneficial effect was present among bulbar onset ALS
      (11.7 versus 23 months). In multivariate analysis management by ALS MDC was
      associated with only a 10% increase in survival probability at 12 months (HR:
      0.91; 95%CI: 0.44-1.89; p = 0.9). CONCLUSIONS: In this population-based series,
      we found that in Southern Italy management of ALS by multidisciplinary clinics
      does not improve survival, regardless of site of symptoms onset.

PMID- 17431706
TI  - Drought tolerance and antioxidant activities in lavender plants colonized by
      native drought-tolerant or drought-sensitive Glomus Species.
AB  - This study compared the effectiveness of four arbuscular mycorrhizal (AM) fungal
      isolates (two autochthonous presumably drought-tolerant Glomus sp and two
      allochthonous presumably drought-sensitive strains) on a drought-adapted plant
      (Lavandula spica) growing under drought conditions. The autochthonous AM fungal
      strains produced a higher lavender biomass, specially root biomass, and a more
      efficient N and K absorption than with the inoculation of similar allochthonous
      strains under drought conditions. The autochthonous strains of Glomus
      intraradices and Glomus mosseae increased root growth by 35% and 100%,
      respectively, when compared to similar allochthonous strains. These effects were
      concomitant with an increase in water content and a decline in antioxidant
      compounds: 25% glutathione, 7% ascorbate and 15% H(2)O(2) by G. intraradices, and
      108% glutathione, 26% ascorbate and 43% H(2)O(2) by G. mosseae. Glutathione and
      ascorbate have an important role in plant protection and metabolic function under
      water deficit; the low cell accumulation of these compounds in plants colonized
      by autochthonous AM fungal strains is an indication of high drought tolerance.
      Non-significant differences between antioxidant activities such as glutathione
      reductase (GR), catalase (CAT) and superoxide dismutase (SOD) in colonized plants
      were found. Thus, these results do not allow the generalization that GR, CAT and
      SOD were correlated with the symbiotic efficiency of these AM fungi on lavender
      drought tolerance. Plants colonized by allochthonous G. mosseae (the less
      efficient strain under drought conditions) had less N and K content than those
      colonized by similar autochthonous strain. These ions play a key role in
      osmoregulation. The AM symbiosis by autochthonous adapted strains also produced
      the highest intraradical and arbuscular development and extraradical mycelial
      having the greatest fungal SDH and ALP-ase activities in the root systems.
      Inoculation of autochthonous drought tolerant fungal strains is an important
      strategy that assured the greatest tolerance water stress contributing to the
      best lavender growth under drought.

PMID- 17431707
TI  - Metaproteomics: a new approach for studying functional microbial ecology.
AB  - In the postgenomic era, there is a clear recognition of the limitations of
      nucleic acid-based methods for getting information on functions expressed by
      microbial communities in situ. In this context, the large-scale study of proteins
      expressed by indigenous microbial communities (metaproteome) should provide
      information to gain insights into the functioning of the microbial component in
      ecosystems. Characterization of the metaproteome is expected to provide data
      linking genetic and functional diversity of microbial communities. Studies on the
      metaproteome together with those on the metagenome and the metatranscriptome will
      contribute to progress in our knowledge of microbial communities and their
      contribution in ecosystem functioning. Effectiveness of the metaproteomic
      approach will be improved as increasing metagenomic information is made available
      thanks to the environmental sequencing projects currently running. More
      specifically, analysis of metaproteome in contrasted environmental situations
      should allow (1) tracking new functional genes and metabolic pathways and (2)
      identifying proteins preferentially associated with specific stresses. These
      proteins considered as functional bioindicators should contribute, in the future,
      to help policy makers in defining strategies for sustainable management of our
      environment.

PMID- 17431708
TI  - The environmental plasmid pQBR103 alters the single-cell Raman spectral profile
      of Pseudomonas fluorescens SBW25.
AB  - Although plasmids are ubiquitous amongst phytosphere pseudomonads, the advantage
      and costs of plasmids for the bacterial host remain unclear. The application of
      single-cell Raman spectral analysis to plasmid-bacterial systems under different
      environmental conditions offers a new means of determining the impact of plasmids
      on host cell physiology, metabolic status, and response to stress.

PMID- 17431709
TI  - Effects of dissolved organic matter photoproducts and mineral nutrient supply on
      bacterial growth in Mediterranean inland waters.
AB  - Sunlight reacts with dissolved organic matter (DOM) modifying its availability as
      bacterial substrate. We assessed the impact of DOM photoproducts and mineral
      nutrient supply on bacterial growth in seven inland waters from the South of
      Spain, where DOM is characterized by low chromophoric content and long residence
      time. Factorial experiments were performed with presence vs absence of DOM
      photoproducts and mineral nutrient supply. In six of the seven experiments, we
      found a significant and negative effect of DOM photoproducts on bacterial growth
      and a significant and positive effect of mineral nutrient supply. The interaction
      of these two factors leaded to a compensation of negative effects of
      photoproducts by availability of mineral nutrients. Dissolved organic matter
      diagenetic status and the ionic environment where organic carbon is dissolved can
      be influencing bacterial DOM processing.

PMID- 17431710
TI  - Analysis of methanogen diversity in the rumen using temporal temperature gradient
      gel electrophoresis: identification of uncultured methanogens.
AB  - A temporal temperature gradient gel electrophoresis (TTGE) method was developed
      to determine the diversity of methanogen populations in the rumen. Tests with
      amplicons from genomic DNA from 12 cultured methanogens showed single bands for
      all strains, with only two showing apparently comigrating bands. Fingerprints of
      methanogen populations were analyzed from DNA extracted from rumen contents from
      two cattle and four sheep grazing pasture. For one sheep, dilution cultures
      selective for methanogens were grown and the culturable methanogens in each
      successive dilution examined by TTGE. A total of 66 methanogen sequences were
      retrieved from bands in fingerprints and analyzed to reveal the presence of
      methanogens belonging to the Methanobacteriales, the Methanosarcinales, and to an
      uncultured archaeal lineage. Twenty-four sequences were most similar to
      Methanobrevibacter ruminantium, five to Methanobrevibacter smithii, four to
      Methanosphaera stadtmanae, and for three, the nearest match was
      Methanimicrococcus blatticola. The remaining 30 sequences did not cluster with
      sequences from cultured archaea, but when combined with published novel sequences
      from clone libraries formed a monophyletic lineage within the Euryarchaeota,
      which contained two previously unrecognized clusters. The TTGE bands from this
      lineage showed that the uncultured methanogens had significant population
      densities in each of the six rumen samples examined. In cultures of dilutions
      from one rumen sample, TTGE examination revealed these methanogens at a level of
      at least 10(5)g(-1). Band intensities from low-dilution cultures indicated that
      these methanogens were present at similar densities to Methanobrevibacter
      ruminantium-like methanogens, the sole culturable methanogens in high dilutions
      (10(6)-10(-10) g(-1)). It is suggested that the uncultured methanogens together
      with Methanobrevibacter spp. may be the predominant methanogens in the rumen. The
      TTGE method presented in this article provides a new opportunity for
      characterizing methanogen populations in the rumen microbial ecosystem.

PMID- 17431712
TI  - Epinephrine-infused CTHA for HCCs.
AB  - BACKGROUND: Changes in the relative arterial flow to hepatocellular carcinomas
      and adjacent normal liver with hepatic arterial epinephrine infusion were studied
      with CT hepatic arteriography (CTHA). METHODS: Data from 31 pathologically
      confirmed hepatocellular carcinomas were retrospectively analyzed in 16 patients
      who simultaneously underwent CT during arterial portography (CTAP) and CTHA for
      examination of liver tumors and then CTHA with hepatic arterial epinephrine
      infusion. RESULTS: Regarding visual analysis, tumor enhancement of hepatocellular
      carcinomas on CTHA after hepatic arterial epinephrine injection changed as
      follows: more clear in 83.9% (26/31), equal in 16.1% (5/31), and less clear in 0%
      (0/31). As for the quantitative analysis, CT attenuation value of hepatocellular
      carcinomas significantly increased after injection of epinephrine (mean increase
      from 225.8 to 333.9 HU; P < 0.0001, paired t test). The CT attenuation value of
      normal liver parenchyma around a tumor significantly decreased after injection of
      epinephrine (mean decrease from 101.1 to 84.6 HU; P < 0.0001, paired t test). The
      tumor-to-liver conspicuity significantly increased after injection of epinephrine
      (mean increase from 124.6 to 249.2 HU; P < 0.0001, paired t test). CONCLUSIONS:
      Hepatic arterial epinephrine infusion changes the relative arterial flow of
      hepatocellular carcinomas.

PMID- 17431713
TI  - Diffusion-weighed MR imaging of pancreatic carcinoma.
AB  - PURPOSE: The aim of this study was to demonstrate the feasibility of body
      diffusion-weighted (DW) MR imaging in the evaluation of a pancreatic carcinoma.
      MATERIAL AND METHODS: In nine normal volunteers and in eight patients with
      pancreatic carcinoma, DW images were obtained on the axial plane scanning with a
      multisection spin-echo-type single-shot echo planar sequence with a body coil.
      Moreover, we measured the apparent diffusion coefficient (ADC) value in a
      circular region of interest (ROI) within the normal pancreas, pancreatic
      carcinoma, and tumor-associated chronic pancreatitis. RESULTS: On the DW images,
      all eight carcinomas were clearly shown as high signal intensity relative to the
      surrounding tissue. The ADC value (x10(-3) mm(2)/s) in the carcinoma was 1.44 +/-
      0.20, which was significantly lower compared to that of normal pancreas (1.90 +/-
      0.06) and tumor-associated chronic pancreatitis (2.31 +/- 0.18). CONCLUSION:
      Diffusion-weighted (DW) images can be helpful in detecting the pancreatic
      carcinoma and accessing the extent of the tumor.

PMID- 17431711
TI  - Use of 16S rRNA gene based clone libraries to assess microbial communities
      potentially involved in anaerobic methane oxidation in a Mediterranean cold seep.
AB  - This study provides data on the diversities of bacterial and archaeal communities
      in an active methane seep at the Kazan mud volcano in the deep Eastern
      Mediterranean sea. Layers of varying depths in the Kazan sediments were
      investigated in terms of (1) chemical parameters and (2) DNA-based microbial
      population structures. The latter was accomplished by analyzing the sequences of
      directly amplified 16S rRNA genes, resulting in the phylogenetic analysis of the
      prokaryotic communities. Sequences of organisms potentially associated with
      processes such as anaerobic methane oxidation and sulfate reduction were thus
      identified. Overall, the sediment layers revealed the presence of sequences of
      quite diverse bacterial and archaeal communities, which varied considerably with
      depth. Dominant types revealed in these communities are known as key organisms
      involved in the following processes: (1) anaerobic methane oxidation and sulfate
      reduction, (2) sulfide oxidation, and (3) a range of (aerobic) heterotrophic
      processes. In the communities in the lowest sediment layer sampled (22-34 cm),
      sulfate-reducing bacteria and archaea of the ANME-2 cluster (likely involved in
      anaerobic methane oxidation) were prevalent, whereas heterotrophic organisms
      abounded in the top sediment layer (0-6 cm). Communities in the middle layer (6
      22 cm) contained organisms that could be linked to either of the aforementioned
      processes. We discuss how these phylogeny (sequence)-based findings can support
      the ongoing molecular work aimed at unraveling both the functioning and the
      functional diversities of the communities under study.

PMID- 17431714
TI  - Extranodal tumor extension to adjacent organs predicts a worse cause-specific
      survival in patients with papillary thyroid carcinoma.
AB  - BACKGROUND: We previously reported that massive extrathyroid extension has an
      independent prognostic value in patients with thyroid papillary carcinoma.
      However, tumor extension to adjacent organs can be observed not only in primary
      tumor but also in metastatic nodes. In this study we investigated the clinical
      significance of extranodal tumor extension to adjacent organs (nodal ex) in
      papillary thyroid carcinoma. METHODS: We classified all cases into three
      categories based on the degree of nodal ex: nodal ex0, no apparent extranodal
      tumor extension; nodal ex1, hard metastatic nodes with perinodal growth extending
      to adjacent organs, which require separation of the nodes from the organs; and
      nodal ex2, metastatic nodes with perinodal growth completely invading the
      adjacent organs and requiring excision of nodes together with these organs. We
      investigated the clinical significance of each grade in 1,692 patients who
      underwent initial surgery for papillary carcinoma between 1987 and 1995. RESULTS:
      The presence of nodal ex was significantly linked to various clinicopathological
      features such as male gender, N1b, large number of metastatic nodes, pT4a, and
      distant metastasis. On univariate analysis, patients with either nodal ex1 or ex2
      showed significantly worse disease-free and cause-specific survival rates,
      although these rates did not differ between patients with nodal ex1 and those
      with nodal ex2. Furthermore, multivariate analysis demonstrated that nodal ex
      independently predicts worse cause-specific survival of these patients.
      CONCLUSIONS: Presence of nodal ex significantly reflects the biologically
      aggressive behaviors of papillary carcinoma and has a prognostic value,
      especially for cause-specific survival of patients.

PMID- 17431715
TI  - Role of centchroman in regression of mastalgia and fibroadenoma.
AB  - OBJECTIVES: Centchroman (Ormeloxifene) is a novel non-steroidal, selective
      antiestrogen. Because of its selective antiestrogen action, centchroman has been
      used for treatment of mastalgia and fibroadenoma. MATERIALS AND METHODS: Benign
      breast disease patients up to 35 years of age attending our surgery outpatient
      department from August 2003 to September 2004 and fulfilling the inclusion
      criterion were included in this study. They were started on centchroman 30 mg on
      alternate days for a period of 3 months and were followed up for 6 months.
      Results were recorded as per clinical examination, visual analog scale (VAS) for
      pain, and ultrasonography for breast lump size. RESULTS: A total of 60 patients
      were included in this pilot study, 42 (70%) of whom had mastalgia with or without
      nodularity, and 18 (30%) had fibroadenoma. Noncyclical pain was recorded in 38
      patients (90%), and cyclical pain was recorded in only 4 (10%) patients. A VAS
      score of 10 was recorded by 33 (80%) patients (severe pain), and the remaining 9
      patients (20%) had VAS scores from 7 to 10. Fibroadenoma size ranged from 1.5 to
      5 cm., single or multiple in one or both breasts. There was a good response in
      the mastalgia group, with a decrease in the VAS scoring from 10 to 3 in 90 % of
      the patients in the first week. Almost all of the patients were painless at the
      end of one month, with complete disappearance of the nodularity. In the
      fibroadenoma group there was a mixed response, with complete disappearance in
      40%, partial regression in 20%, and no response at all in the remaining 40%.
      There were very few side effects. CONCLUSIONS: Centchroman is a safe nonsteroidal
      drug for the treatment of mastalgia and fibroadenoma. It has shown good results
      in mastalgia and is a safe drug as compared to the drugs of choice used at
      present (danazole and bromocriptine). Further randomized studies are in progress
      and are needed to determine its definitive role in this patient group.

PMID- 17431718
TI  - The use of the Santulli enterostomy.

PMID- 17431717
TI  - An evidence-based review of poorly differentiated thyroid cancer.
AB  - BACKGROUND: Poorly differentiated thyroid cancer (PDTC) presents the
      endocrinologist and surgeon with challenges of recognition and treatment given
      the lack of consensus on histopathologic definition and limited literature on
      surgical and nonsurgical treatment. METHODS: We offer an operational pathologic
      definition for PDTC, which should help guide future work in this area. Poorly
      differentiated thyroid cancer should include insular and trabecular variants but
      should not include solid type lesions (included by other workers) or more
      differentiated tumors that may have poor prognosis such as tall cell, columnar,
      diffuse sclerosing, and oncocytic lesions. Systematic evidence-based literature
      reviews focusing on two questions were carried out: (1) is PDTC associated with
      an intermediate prognosis relative to anaplastic and WDTC? and (2) What are the
      postoperative treatment options for poorly differentiated thyroid cancer?
      CONCLUSIONS: We have found level IV evidence that PDTC is intermediate between
      WDTC and anaplastic cancers in terms of prognosis. It represents a disease where
      appropriate administration of aggressive treatment not typically necessary for
      routine WDTC and not effective for anaplastic disease may uniquely result in
      substantial benefit. Limited level IV data show conflicting results regarding
      131I treatment benefit. Given lack of morbidity and potential for benefit, we
      recommend that 131I therapy be considered in all patients postoperatively.
      Recommendation regarding external beam radiotherapy (XRT) is based primarily on
      extrapolation from studies in forms of poor-prognosis WDTC where substantial data
      exist regarding treatment benefit. We recommend that external beam treatment be
      considered in all patients with PDTC with T3 tumors without distant metastasis,
      all patients with T4 tumors, and all patients with regional lymph node
      involvement.

PMID- 17431720
TI  - Comparison of algorithms to enhance spicules of spiculated masses on mammography.
AB  - We have developed an algorithm for enhancement of spicules of spiculated masses,
      which uses the discrete radon transform. Previously, we employed a commonly used
      method to compute the discrete radon transform, which we refer to as the DRT.
      Recently, a new, more exact method to compute the discrete radon transform was
      developed by Averbuch et al, which is called the fast slant stack (FSS) method.
      Our hypothesis was that this new formulation would help to improve our
      enhancement algorithm. To test this idea, we conducted multiple two-alternative
      forced-choice observer studies and found that most observers preferred the
      enhanced images generated with the FSS method.

PMID- 17431719
TI  - Impact of IVC housing on emotionality and fear learning in male C3HeB/FeJ and
      C57BL/6J mice.
AB  - Housing conditions are known to influence laboratory animal behavior. However, it
      is not known whether housing mice in individually ventilated cages (IVCs) to
      maintain optimal hygienic conditions alters behavioral baselines established in
      conventional housing. This issue is important with regard to comparability and
      reproducibility of data. Therefore, we investigated the impact of IVC housing on
      emotionality and fear learning in male C3HeB/FeJ (C3H) and C57BL/6J (B6J) mice
      housed singly either in conventional type II cages with wire bar lids
      (Conventional), or in IVCs of the same size, but with smooth, untextured lids
      (IVC classic), thus acoustically attenuated from external stimuli and with
      limited climbing facilities compared to Conventional. To evaluate the role of
      climbing, additional mice were kept in IVCs with lids having wire bars ("grid")
      added to the inner surface (IVC grid). Spontaneous behavior, sensorimotor
      behavior, and fear learning were measured. IVC housing reduced activity and
      enhanced anxiety-related behavior in both strains, whereas grooming latency was
      reduced in B6J only. IVC housing increased Acoustic Startle Response in C3H but
      not in B6J mice. The "grid" did not compensate for these IVC housing effects. In
      contrast, B6J mice in IVC grid performed best in fear potentiated startle while
      B6J mice in IVC classic performed the worst, suggesting that climbing facilities
      combined with IVC housing facilitate FPS performance in singly-housed B6J males.
      Our data show that IVC housing can affect behavioral performance and can modulate
      behavioral parameters in a general and a strain-specific manner, thus having an
      impact on mouse functional genomics.

PMID- 17431721
TI  - Prospective, five-year follow-up study of patients with symptomatic uncomplicated
      diverticular disease.
AB  - PURPOSE: The natural history of diverticular disease is largely unknown. Most
      studies are retrospective and treatment recommendations are derived from outdated
      literature. This study was a prospective, long-term assessment of the development
      of complications in patients with symptomatic diverticular disease. METHODS: All
      patients with a confirmed diagnosis of symptomatic diverticular disease between
      August 1999 and April 2001 were followed up prospectively for an average of five
      years. Hospital computerized discharges were assessed for any subsequent elective
      or emergency admission for diverticular disease-related complications, including
      surgical intervention. A telephone questionnaire was conducted on all patients
      and/or their family physician looking specifically for symptoms, complications,
      and surgical intervention. RESULTS: A total of 163 patients (106 females) were
      identified (median age, 74 (interquartile range, 64-80) years). The diagnosis was
      confirmed through colonoscopy (n = 106), flexible sigmoidoscopy (n = 57), and
      barium enema (n = 31). Nineteen were lost to follow-up and a further 19 died from
      unrelated causes. Twenty-five were excluded. After the initial diagnosis, two
      patients (1.7 percent) subsequently presented with an episode of diverticulitis,
      which was treated conservatively. A single patient (0.8 percent) required surgery
      for chronic symptoms. One hundred sixteen patients (97 percent) had no or mild
      symptoms after a median follow-up of 66 months. CONCLUSIONS: In this prospective
      long-term study, symptomatic uncomplicated diverticular disease seems to run a
      long-term benign course with a very low incidence of subsequent complications.
      Symptomatic disease, acute diverticulitis, and complicated diverticular disease
      seem to constitute distinct clinical entities with little crossover between
      groups.

PMID- 17431722
TI  - A nonsurgical means of fecal diversion: the Zassi Bowel Management System.
AB  - PURPOSE: Patients with perineal burns and immobile hospitalized patients with
      severe excoriation from incontinence caused by excessive diarrhea pose difficult
      management problems, frequently requiring stoma formation. The Zassi Bowel
      Management System (Zassi Medical Evolutions, Fernandina Beach, Florida)
      multichannel intrarectal catheter was evaluated for its safety and its ability to
      divert feces away from perineal skin to allow wound and skin healing. METHODS: A
      prospective cohort study was conducted on inpatients from the Burns and Geriatric
      Units. Patients with previous rectal disease were excluded. Perineal skin and
      wound healing was measured before and after tube insertion by using the perianal
      disease activity index score. Data regarding patient comfort, wound
      contamination, dressing changes, bed linen changes, and adverse events were
      collected. Proctoscopy was performed before and after tube insertion. RESULTS:
      Twenty-two tubes were inserted in 20 patients (7 perineal burns, 13 severe
      perineal excoriations). Mean perianal disease activity index scores reduced from
      14 to 6.4 (P<0.0001) after tube insertion. Mean dressing changes reduced from 3.3
      to 1.5 times per day (P<0.01), and mean bed linen changes in the incontinent
      patients reduced from 9.3 to 1.2 times per day (P<0.0001). Mean duration of
      rectal intubation was 14 days. Proctoscopy after tube removal was normal in all
      cases. One patient developed a superficial ulcer on the buttock from retention
      strapping. CONCLUSIONS: The Zassi Bowel Management System tube allows diversion
      of feces away from the perineum for wound healing. It is safe, effective, and may
      help avoid stoma formation.

PMID- 17431723
TI  - A meta-analysis of quality of life for abdominoperineal excision of rectum versus
      anterior resection for rectal cancer.
AB  - BACKGROUND: Avoiding a permanent stoma following rectal cancer excision is
      believed to improve quality of life (QoL), but evidence from comparative studies
      is contradictory. The aim of this study was to compare QoL following
      abdominoperineal excision of rectum (APER) with that after anterior resection
      (AR) in patients with rectal cancer. METHODS: A literature search was performed
      to identify studies published between 1966 and 2006 comparing values of QoL
      following APER and AR. Random-effect meta-analysis was used to combine the data.
      Sensitivity analyses were performed for larger studies, those of higher quality
      and those using self-administered QoL questionnaires. RESULTS: The outcomes for
      1,443 patients from 11 studies, of whom 486 (33%) underwent APER, were included.
      QoL assessments were made at periods of up to 2 years following surgery. There
      was no significant difference in global health scores between APER and AR.
      Vitality (WMD -9.82; 95% CI -27.01, -2.04, P = 0.01) and sexual function (WMD 
      2.73; 95% CI -4.93, -0.64, P = 0.01) were improved in the AR patients. Patients
      with low AR had improved physical function scores in comparison with APER
      patients (WMD -4.67; 95% CI -9.10, -0.23; P = 0.004). Cognitive (WMD 3.57; 95% CI
      1.41, 5.73; P < 0.001) and emotional function scores (WMD 3.51; 95% CI 1.40,
      5.62; P < 0.001) were higher for APER patients. CONCLUSION: Overall, when
      comparing APER with AR, we identified no differences in general QoL following the
      procedures. Individualisation of care for rectal cancer patients is essential,
      but a policy of avoidance of APER cannot currently be justified on the grounds of
      QoL alone.

PMID- 17431724
TI  - The role of intra-arterial calcium stimulation test with hepatic venous sampling
      (IACS) in the management of occult insulinomas.
AB  - BACKGROUND: Occult insulinomas remain a clinical challenge. Specifically designed
      protocols are necessary to aid detection and facilitate a focused pancreatic
      exploration. METHODS: Seventeen non-multiple endocrine neoplasia (non-MEN)
      patients referred to this medical center in the past 10 years because of
      equivocal diagnosis, failure of previous operation or difficulty in localization
      for insulinomas were studied. A routine intra-arterial calcium stimulation test
      with venous sampling (IACS test) was done for lesion localization. An exploratory
      laparotomy with intraoperative ultrasound (IOUS) examinations was performed.
      RESULTS: Preoperative imaging (sonography, high-resolution computed tomography
      scan, and magnetic resonance imaging) found six insulinomas, and IOUS found an
      additional six in the pancreatic regions; all were compatibly indicated by the
      IACS test. The remaining five patients with occult lesions by IOUS were treated
      by 40% (1) or 60-70% (4) distal pancreatectomies when insulin gradients were
      demonstrated on calcium stimulation to the splenic or to the superior mesenteric
      artery, respectively, and nesidioblastosis was found in each pathology
      examination. There were no complications related to the arterial stimulation and
      venous sampling (ASVS) test. No patient had recurrent hyperinsulinism, permanent
      morbidity, or mortality from surgery. CONCLUSIONS: IACS test helps in the
      diagnosis of equivocal pancreatogenous hypoglycemia, indicating the pancreatic
      region of priority exploration and guiding a pancreatic resection.

PMID- 17431725
TI  - Comparison of functional and surgical outcomes of laparoscopic-assisted colonic J
      pouch versus straight reconstruction after total mesorectal excision for lower
      rectal cancer.
AB  - BACKGROUND: To compare the functional and surgical outcomes of colonic J-pouch
      and straight anastomosis in the context that both reconstruction procedures were
      performed laparoscopically. METHODS: The present study was a randomized
      prospective clinical trial. Patients with lower rectal cancer requiring
      laparoscopic total mesorectal excision were equally randomized to either
      laparoscopic-assisted colonic J-pouch reconstruction or laparoscopic straight end
      to-end anastomosis. The techniques of the laparoscopic-assisted colonic J-pouch
      reconstruction are shown in the attached video. The primary end point was the
      comparison of functional results in both reconstruction methods. The secondary
      end points included the safety (surgical morbidity and mortality), surgical
      efficiency, and postoperative recovery. RESULTS: A total of 48 patients were
      recruited within 2-year periods, in consideration of statistical power of 90% for
      comparison. There was no marked difference between patient groups undergoing
      colonic J-pouch surgery (n = 24) and straight anastomosis (n = 24) in various
      demographic and clinicopathogic parameters. The anorectal function of patients by
      colonic J-pouch were better than those by straight anastomosis in 3 months after
      operation, as evaluated by stool frequency (mean +/- standard deviation: 4.0 +/-
      2.0 vs. 7.0 +/- 2.4 times/day, P < .001); use of antidiarrheal agents (29.2% [n =
      7] vs. 75.0% [n = 18], P = .004); and perineal irritation (45.8% [n = 11] vs.
      79.2% [n = 19], P = .037). Because of the relatively better bowel function in
      immediate postoperative period, patients by colonic J-pouch reconstruction were
      less disabled after surgery and had quicker return to partial activity (P =
      .039), full activity (P < .001), and work (P < .001). Both reconstruction methods
      were performed with similar amounts of blood loss, complication rates, and
      postoperative recovery. However, the operation time was significantly longer in
      the colonic J-pouch group (274.4 +/- 34.0 vs. 202.0 +/- 28.0 minutes, P < .001).
      CONCLUSIONS: Because laparoscopic-assisted creation of a colonic J-pouch achieved
      better short-term functional results of the anorectum and did not increase
      surgical morbidity, as compared with laparoscopic straight anastomosis, this
      reconstruction procedure could be recommended to patients with lower rectal
      cancer requiring laparoscopic total mesorectal excision.

PMID- 17431726
TI  - Resection of isolated pelvic recurrences after colorectal surgery: long-term
      results and predictors of improved clinical outcome.
AB  - BACKGROUND: Recurrence in the pelvis after resection of a rectal or rectosigmoid
      cancer presents a dilemma. Resection offers the only reasonable probability for
      cure, but at the cost of perioperative morbidity and potential mortality.
      Clinical decision making remains difficult. METHODS: Patients resected with
      curative intent for isolated pelvic recurrences after curative colorectal surgery
      from 1988 through 2003 were reviewed retrospectively. Clinical and pathologic
      factors, salvage operations, and complications were recorded. The primary
      measured outcome was overall survival. Univariate and multivariate analyses were
      conducted to identify prognostic factors of improved outcome. RESULTS: Ninety
      patients underwent an attempt at curative resection of a pelvic recurrence with
      median follow-up of 31 months. Complications occurred in 53% of patients.
      Operative mortality was 4.4% (4 of 90). Median overall survival was 38 months,
      and estimated 5-year survival was 40%. A total of 51 of 86 patients had known
      recurrences (15 local, 16 distant, 20 both). Multivariate analysis revealed that
      preoperative carcinoembryonic antigen level and final margin status were
      statistically significant predictors of outcome. CONCLUSIONS: The resection of
      pelvic recurrences after colorectal surgery for cancer can be performed with low
      mortality and good long-term outcome; however, morbidity from such procedures is
      high. Low preoperative carcinoembryonic antigen and negative margin of resection
      predict improved survival.

PMID- 17431727
TI  - Comparison of molecular markers of hypoxia and imaging with (60)Cu-ATSM in cancer
      of the uterine cervix.
AB  - PURPOSE: To determine if hypoxia-related molecular markers are associated with
      (60)Cu labeled diacetyl-bis (N4 -methylthiosemicarbazone); ((60)Cu-ATSM) imaging
      of tumor hypoxia in cervical cancer. PROCEDURES: Fifteen patients were enrolled
      in a prospective study and underwent evaluation of tumor hypoxia with positron
      emission tomography (PET) using (60)Cu-ATSM. (60)Cu-ATSM-PET imaging was compared
      with the expression of tissue molecular markers, which included vascular
      endothelial growth factor (VEGF), cyclo-oxygenase-2 (COX-2), epidermal growth
      factor receptor (EGFR), carbonic anyhdrase IX (CA-9), and apoptotic index.
      RESULTS: Six patients had hypoxic tumors determined by (60)Cu-ATSM, and nine had
      non-hypoxic tumors. The 4-year overall survival estimates were 75% for patients
      with non-hypoxic tumors and 33% for those with hypoxic tumors (p = 0.04).
      Overexpression of VEGF (p = 0.13), EGFR (p = 0.05), CA-9 (p = 0.02), COX-2 (p =
      0.08), and the presence of apoptosis (p = 0.005) occurred in patients with
      hypoxic tumors. Cox proportional hazards modeling demonstrated hypoxia as
      determined by (60)Cu-ATSM to be a significant independent predictor of tumor
      recurrence (p = 0.0287). CONCLUSIONS: (60)Cu-ATSM hypoxia was correlated with
      overexpression of VEGF, EGFR, COX-2, CA-9, an increase in apoptosis, and a poor
      outcome.

PMID- 17431728
TI  - A 10-day course of SPA therapy is beneficial for people with severe knee
      osteoarthritis. A 24-week randomised, controlled pilot study.
AB  - The objective of this study was to test if spa therapy can play a role in the
      management of severe knee osteoarthritis (OA). Twenty patients with
      radiologically and clinically severe knee OA were randomly assigned into spa and
      drug therapy groups. Spa group (n = 10) traveled to a spa town and stayed at a
      hotel for a 10-day spa therapy course. They followed a balneotherapy regimen
      including thermal pool baths at 37 degrees C for 20 min two times daily. Drug
      therapy group (n = 10) stayed at home and followed their individually prescribed
      drug therapy (NSAIDs and paracetamol). Patients were assessed at baseline (week
      0), after spa therapy at 2 weeks (week 2) and during follow-up period at 12 (week
      12) and 24 (week 24) weeks by a blinded investigator. Patients assessed with
      Lequesne algofunctional index (LAFI), pain (visual analogue scale, VAS),
      patient's and investigator's global evaluation (VAS), ten-stairs stepping up and
      down time, 15 m walking time and three times squatting up and down time.
      Significant improvement in pain and LAFI scores were found at week 2, week 12 and
      week 24 in the spa therapy group compared to baseline. Comparing the two group
      differences, spa therapy was superior to drug therapy in pain reduction and in
      physician's global assessment at all time points. This superiority was also found
      in LAFI scores and patients' global assessments at week 12 and week 24. A 10-day
      course of spa therapy may be beneficial in short- and medium-term up to 24 weeks
      by reducing pain and improving functional status and overall well-being in
      patients with severe knee OA and may be considered as an effective therapeutic
      tool for such patients in countries like Turkey where it is widely available and
      (at least partly) reimbursed.

PMID- 17431730
TI  - Adverse effects reported in epilatory ruby laser treatment.
AB  - A retrospective study was conducted to investigate the incidence of reported
      adverse responses after epilatory laser treatment to control the growth of facial
      hair in patients with polycystic ovary syndrome. Forty-eight patients received a
      median of 6 (range 2-11) treatments with an Aesculap ruby laser during a 704 day
      monitoring period at Salisbury District Hospital. Nine adverse skin responses
      such as blistering, scabbing, sustained localised erythematous reactions or
      hyperpigmentation were reported. The energy output of the laser was also recorded
      at the start of every clinical session during this period using an external
      energy meter. The measured energy output of the laser was plotted alongside
      incidents of adverse responses, although no statistically significant correlation
      was found. The question of whether or not some adverse effects in ruby laser
      treatment can be attributed to laser performance remains open.

PMID- 17431729
TI  - Association of tri-nucleotide (CAG and GGC) repeat polymorphism of androgen
      receptor gene in Taiwanese women with refractory or remission rheumatoid
      arthritis.
AB  - We investigated the relationship between CAG and GGC repeat polymorphism of the
      androgen receptor (AR) gene and rheumatoid arthritis (RA) in female patients with
      different disease subtypes. This case-control study enrolled 215 women in three
      groups: RA patients refractory to standardized therapy (n = 51); RA patients at
      complete remission phase (n = 60); and healthy controls (n = 104). CAG and GGC
      repeat lengths were determined by automated fluorescence-based DNA fragment
      sizing method. Demographic data, allele lengths, allele distribution, and
      zygosity status of CAG/GGC repeats were assessed for the three groups. Refractory
      RA patients tend to have a significantly younger onset age of RA and more
      elevated erythrocyte sedimentation rates than do remission RA patients. Mean and
      median values of CAG and GGC repeat lengths are similar in both RA and control
      patients. However, RA patients harboring any long CAG alleles with more than 23
      repeats had an increased risk of a refractory course, whereas differences in risk
      were not observed between these patients and RA subtypes harboring any long GGC
      alleles with more than 16 repeats. In addition, the homozygous frequency of CAG
      but not GGC alleles was lower in refractory RA than in remission RA patients or
      in controls (p = 0.042). Neither CAG nor GGC repeat lengths had a significant
      relationship with rheumatoid factor reactivity. Our observations indicate that
      short CAG repeats of the AR gene with higher transactivation activity may have
      protective effects against refractory course of RA development and that
      homozygous frequency of CAG alleles may be involved in the disease remission
      subtype. In contrast, lack of association of GGC polymorphism and RA was also
      observed. Together, these data imply that CAG but not GGC alleles in the AR
      polymorphism may play an important role in modulating the disease pattern of RA
      among Taiwanese women.

PMID- 17431731
TI  - Long chain fatty acid oxidation defects in children: importance of detection and
      treatment options.
AB  - BACKGROUND: Mitochondrial beta oxidation plays a major role in energy production.
      Long chain fatty acid oxidation defects include deficiency of the trifunctional
      protein (rare) or more commonly defects of the long chain 3-hydroxy acyl-CoA
      dehydrogenase enzyme (LCHAD). These long chain defects have variable
      presentations, they may present in the neonate or infant with sudden death,
      hepatopathy (Reyes disease), hypoketotic hypoglycaemia, rhabdomyolysis, myopathy,
      cardiomyopathy and with late complications such as peripheral neuropathy,
      pigmentary retinopathy, retinal degeneration and progressive visual loss. The
      correct diagnosis at presentation is not only life saving but also allows for the
      appropriate dietary and other intervention, which may have major effects on
      outcome. AIM: Three case reports of patients with long chain fatty acid oxidation
      defects who have shown significant benefits from treatment are reported.
      CONCLUSIONS: These paediatric presentations illustrate the clinical heterogeneity
      of long chain fatty acid oxidation defects and opportunities for effective
      management if correctly diagnosed.

PMID- 17431732
TI  - Leg bone pain syndrome in a patient with ulcerative colitis treated with
      cyclosporin.
AB  - BACKGROUND: Leg bone pain syndrome is an unusual condition associated with the
      use of calcineurin antagonists, initially described in patients receiving
      allograft transplantation. AIM: To describe the first known reported case of leg
      bone pain syndrome in a patient with ulcerative colitis receiving cyclosporin.
      RESULTS: Investigations revealed no diagnostic features. Calcium channel blocker
      was used successfully in the treatment of this condition. CONCLUSION: In the
      absence of diagnostic investigations, a high index of clinical suspicion is
      needed to diagnose and successfully manage leg bone pain syndrome. This may
      prevent further complications such as osteonecrosis that may arise.

PMID- 17431733
TI  - Topological and chronological features of the impairment of glucose metabolism
      induced by 1-methyl-4-phenylpyridinium ion (MPP+) in rat brain slices.
AB  - 1-Methyl-4-phenylpyridinium (MPP(+)) was added directly to fresh rat brain slices
      and the dynamic changes in the cerebral glucose metabolic rate (CMRglc) were
      serially and two-dimensionally measured with [(18)F]2-fluoro-2-deoxy-D-glucose as
      a tracer. MPP(+) dose-dependently increased CMRglc, reflecting enhanced
      glycolysis compensating for the decrease in aerobic metabolism. While the CMRglc
      enhancement induced by MPP(+) (<10 microM) was restricted to the striatum, MPP(+)
      (>or=10 microM) induced a significant CMRglc enhancement in all brain regions.
      MPP(+) at high concentration (1 mM) eventually initiated rapid metabolic
      collapse, with failure to sustain anaerobic glycolysis.

PMID- 17431734
TI  - Continuous delivery of rotigotine decreases extracellular dopamine suggesting
      continuous receptor stimulation.
AB  - Rotigotine, a non-ergolinic dopamine receptor agonist for treatment of
      Parkinson's disease was continuously administered over 48 h (0.5 mg/kg s.c., slow
      release formulation) to conscious rats striatally implanted with a microdialysis
      probe. Subsequently, the levels of rotigotine increased to a maximum of 3.42 +
      2.1 nmol/l and remained at a level of 2.81 +/- 0.82 nmol/l for 48 h.
      Concomitantly, the dopamine levels consistently decreased to 20% of the control
      level. This suggests that the sustained administration of rotigotine provides
      stable extracellular drug levels in the striatum resulting in continuous
      stimulation of dopamine receptors.

PMID- 17431735
TI  - Studies on the insulinomimetic effects of benzylamine, exogenous substrate of
      semicarbazide-sensitive amine oxidase enzyme in streptozotocin induced diabetic
      rats.
AB  - Semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO) is
      believed to be a bifunctional membrane protein. It is localized extracellularly
      and preferentially oxidizes short chain primary amines to aldehydes, hydrogen
      peroxide and ammonia, but also functions as an adhesion molecule, which is
      involved in leukocyte migration. Serum SSAO activity is increased in diabetic
      patients and animals and the aldehydes formed in the enzyme reaction may
      contribute to vascular damage. However, administration of exogenous substrates
      has been shown to improve glucose tolerance and reduce hyperglycaemia in diabetic
      animals. Hydrogen peroxide and/or its vanadate complexes have been suggested
      responsible for these effects. Streptozotocin induced diabetic rats were treated
      with benzylamine (BZA) +/- vanadate (V) or insulin. In contrast to insulin, BZA +
      V treatment did not reduce HbA(1C) levels. However, it reduced the elevated serum
      SSAO activity, decreased the accumulation of advanced-glycation end products and
      increased the bioavailability of nitric oxide in diabetic animals, similarly to
      insulin. BZA alone did not affect any of these parameters.

PMID- 17431736
TI  - Alteration of serum semicarbazide-sensitive amine oxidase activity in chronic
      renal failure.
AB  - Despite recent intensive investigations, physiological and pathological role of
      semicarbazide-sensitive amine oxidase (SSAO) is far from clear. In this study,
      serum SSAO activity was determined, radiochemically, in various groups of uremic
      patients: haemodialysed (HD), peritoneally dialysed (PD) and those receiving
      conservative treatment but still not dialysed (ND), as well as in controls.
      Reduced enzyme activity was found in HD uremic patients before and after dialysis
      treatment, compared to controls (5260 +/- 862 and 6011 +/- 958 pmol/h/ml vs. 8601
      +/- 283 pmol/h/ml, p < 0.01 and p < 0.05, respectively). The activity was
      slightly lower in PD, and normal in ND patients. In HD patients SSAO activity was
      also determined by an assay based on the formation of hydrogen peroxide, and was
      found to be elevated compared to controls (2384 +/- 323 pmol/h/ml vs. 1437 +/- 72
      pmol/h/ml, p < 0.05). The elevated serum SSAO activity measured through the
      detection of the enzyme-generated hydrogen peroxide in HD patients might indicate
      its contribution to the accelerated atherosclerotic disease observed in uremia.

PMID- 17431737
TI  - Prevalence of antibody to hepatitis E virus among wild sika deer, Cervus nippon,
      in Japan.
AB  - We examined 976 sika deer serum samples, 159 liver tissue samples and 88 stool
      samples collected from 16 prefectures in Japan, and performed ELISA and RT-PCR
      assays to detect antibodies to HEV and HEV RNA, respectively. Although 25 (2.6%)
      of 976 samples were positive for anti-HEV IgG, the antibody titers were very low.
      The OD values ranged between 0.018 and 0.486, forming a single distribution
      rather than a bimodal distribution, suggesting that the antibody detected in this
      study was not induced by HEV infection, or that deer have low sensitivity to HEV.
      HEV RNA was not detected in these samples, also suggesting that deer may not play
      a role as an HEV reservoir.

PMID- 17431738
TI  - Molecular characterization of banana streak acuminata Vietnam virus isolated from
      Musa acuminata siamea (banana cultivar).
AB  - An isolate of banana streak virus (BSV) that does not also occur as an integrant
      in the Musa balbisiana genome was sought in order to investigate the biological
      role of BSV in the evolution of either the Musa genome or of the virus itself. We
      isolated BSV virions from a Musa acuminata siamea accession from Vietnam and
      sequenced the entire viral genome. The molecular organization is similar to that
      described for other BSV but slightly larger (7801 bp vs. 1611-7568 bp), and ORF I
      has a non-conventional start codon. This genome was sufficiently different to
      propose it as a member of a distinct species named Banana streak virus strain
      acuminata Vietnam (BSAcVNV).

PMID- 17431739
TI  - Symptom-onset dosing with citalopram in the treatment of premenstrual dysphoric
      disorder (PMDD): a case series.
AB  - The efficacy and tolerability of symptom-onset dosing with citalopram in the
      treatment of premenstrual dysphoric disorder (PMDD) was evaluated in an open
      trial. Eight outpatients, aged 18-45 years and diagnosed with PMDD, were treated
      with 10-20 mg of citalopram from the start of premenstrual symptoms until the
      onset of menses. Primary efficacy variables were the premenstrual tension scale
      (PMTS-O) and the clinical global impression of improvement (CGI). Treatment was
      associated with significant improvement in PMDD symptoms (p < 0.001).

PMID- 17431740
TI  - Missed antenatal depression among high risk women: a secondary analysis.
AB  - Psychiatrically high-risk women were recruited for a postpartum depression
      prevention trial. Participants were screened at entry (20-26 weeks gestation) by
      a psychiatrist prior to receiving randomized treatment. Of the 31 patients who
      did not complete the study, 10 (33%) were dropped because of diagnosed
      depression. Only two women developed major depression in the postpartum period.
      Our data suggests, among high-risk women, obstetric care providers may be
      overlooking up to one fifth of women with current major depression.

PMID- 17431741
TI  - The relevance of sleep abnormalities to chronic inflammatory conditions.
AB  - Sleep is vital to health and quality of life while sleep abnormalities are
      associated with adverse health consequences. Nevertheless, sleep problems are not
      generally considered by clinicians in the management of chronic inflammatory
      conditions (CIC) such as asthma, RA, SLE and IBD. To determine whether this
      practice is justified, we reviewed the literature on sleep and chronic
      inflammatory diseases, including effects of sleep on immune system and
      inflammation. We found that a change in the sleep-wake cycle is often one of the
      first responses to acute inflammation and infection and that the reciprocal
      effect of sleep on the immune system in acute states is often protective and
      restorative. For example, slow wave sleep can attenuate proinflammatory immune
      responses while sleep deprivation can aggravate those responses. The role of
      sleep in CIC is not well explored. We found a substantial body of published
      evidence that sleep disturbances can worsen the course of CIC, aggravate disease
      symptoms such as pain and fatigue, and increase disease activity and lower
      quality of life. The mechanism underlying these effects probably involves
      dysregulation of the immune system. All this suggests that managing sleep
      disturbances should be considered as an important factor in the overall
      management of CIC.

PMID- 17431742
TI  - Nitric oxide in upper airways inflammatory diseases.
AB  - In the human respiratory tract, the main production sites of exhaled nitric oxide
      (NO) are the nose and paranasal sinuses. In the upper airways, NO has been
      suggested to be involved at different levels with regulatory, protective,
      defensive or deleterious effects. Therefore, we review some aspects of the
      origin, metabolism, and functions of NO in the upper airways, together with the
      role of NO in some upper airways inflammatory diseases. Furthermore, we discuss
      the recent improvements in nasal NO measurements, which may be useful to better
      characterize the involvement of the NO produced by nose and paranasal sinuses in
      upper airways inflammatory diseases such as allergic rhinitis, nasal polyposis,
      sinusitis, primary ciliary dyskinesia, and cystic fibrosis.

PMID- 17431743
TI  - Bacterial components regulate the expression of Toll-like receptor 4 on human
      mast cells.
AB  - OBJECTIVES AND DESIGN: The aim of this study was to investigate whether the
      exposure of mast cells (MCs) to bacterial components affects the expression of
      Toll-like receptor (TLR) 4, and to elucidate the behavior of MCs during the early
      response to infection. MATERIALS: Two human MC lines, HMC-1 and LAD2, were
      employed. Messenger RNA expression was observed by RT and real-time PCR. TLR4
      expression was determined by Western blotting. TNF-alpha secretion was analyzed
      with ELISA. The degranulation ratio was measured with betahexosaminidase assay.
      RESULTS: Although bacterial components increased TLR4 mRNA, only
      lipopolysaccharide (LPS) augmented the TLR4 protein expression. LAD2 pre-treated
      with LPS for 8 h resulted in 2-fold increased TNF-alpha secretion on LPS
      restimulation. CONCLUSION: These results suggest that the exposure of MCs to LPS
      may reinforce the innate immune system due to up-regulation of MC TLR4, followed
      by increased TNF-alpha release.

PMID- 17431744
TI  - Effect of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. leaf on
      inflammatory cytokine and mediator induction from alveolar macrophages of chronic
      bronchitic rats.
AB  - OBJECTIVE: The study was to evaluate the effect of triterpene acids of Eriobotrya
      japonica (thunb.) lindl. leaf (TAL) on inflammatory cytokine and mediator
      expression in alveolar macrophages (AM) of chronic bronchitic (CB) rats. METHODS:
      CB was induced by endotracheal instillation of lipopolysaccharide (LPS) followed
      by Bacillus Calmette Guerin (BCG) injection via the caudal vein one week later.
      Treatment groups received TAL at there different doses (50, 150, or 450 mg/kg
      daily i. g.), Ketotifen fumarate (5 mg/kg daily i. g.) or dexamethasone (1.2
      mg/kg daily i. g.) for two weeks, 7 days after LPS injection. AM were then
      isolated and incubated for 24 h. IL-1, TNF-alpha and PGE2 levels in cultured
      supernatants were measured by thymocyte co-stimulating assay and
      radioimmunoassay. Immunocytochemistry staining and western-blot were used for
      intracellular location and activation of p65 subunit of NF-kB. LTB(4) level was
      analyzed by reverse-phase high performance liquid chromatography (RP-HPLC).
      RESULTS: The levels of TNF-alpha, IL-1, NF-kB, PGE2 and LTB(4) expression in AM
      of TAL groups were significantly decreased compared to the CB group (P < 0.05 or
      P < 0.01), in a dose dependent manner. CONCLUSION: TAL inhibited NF-kB activation
      in AM from CB rats and led to down regulation of TNF-alpha, IL-1, PGE(2) and
      LTB(4) expression, which might be a mechanism for its anti-inflammatory effects
      in CB rats.

PMID- 17431746
TI  - Serotonin content is elevated in the immune cells of histidine decarboxylase gene
      knock-out (HDCKO) mice. Focus on mast cells.
AB  - OBJECTIVE: Biogenic amines, histamine and serotonin are present in the granules
      and nucleus of mast cells. We wanted to study the presence, amount and
      localization of serotonin in mast cells and other cells of the immune system,
      under conditions of histamine deficiency caused by knock out of histamine
      decarboxylase gene (HDCKO). METHODS: Wild type and histamine deficient HDCKO mice
      were studied for serotonin content of the immune cells (lymphocytes as well as
      the monocyte-granulocyte-mast cell group) using flow cytometry and confocal
      microscopy. Groups of mice were kept either on complete rodent chow or on a
      histamine-free diet for a month before the experiments. RESULTS: The amount of
      serotonin was significantly higher in the KO animals, irrespective of the diet.
      Confocal microscopy demonstrated the presence of serotonin in the nucleus of mast
      cells in the wild type animals, while it was not present in the KO mice.
      Furthermore, in the cytoplasm (granules) of KO mast cells a bright fluorescence
      was observed in contrast to the pale fluorescence of wild animals. CONCLUSION: It
      seems likely that serotonin replaces the deficient histamine in the heparin
      biogenic amine complex in the mast cell granules.

PMID- 17431745
TI  - Role of NO/cGMP/KATP pathway in antinociceptive effect of sildenafil in zymosan
      writhing response in mice.
AB  - OBJECTIVE: Previous studies have found that sildenafil produces antinociception
      in experimental models. This work was undertaken to determine the participation
      of the NO/cGMP/K(ATP) pathway in the antinociception induced by sildenafil.
      METHODS AND RESULTS: The antinociceptive effect of sildenafil was determined in
      the zymosan-induced writhing response in mice. Sildenafil (1-30 mg/kg; i. p.),
      given 30 min before zymosan (1 mg/animal; i. p.), inhibited the writhing response
      (5.0 +/- 1.3 versus 26.6 +/- 2.7; p < 0.001) in a dose-dependent manner. L-NAME
      (30 mg/kg; s. c.) significantly (p < 0.05) reversed this effect (16.6 +/- 3.1
      versus 6.4 +/- 1.6) and L-arginine (200 mg/kg; i. p.) prevented the L-NAME effect
      (6.8 +/- 0.8 versus 16.6 +/- 3.1; p < 0.05). ODQ (0,3-1 mg/kg; i. p.) and
      glybenclamide (0.3-1 mg/kg; p. o.) pre-treatment significantly (p < 0.01)
      inhibited the antinociceptive effect of sildenafil (18.0 +/- 1.7 versus 2.1 +/-
      1.0 and 5.5 +/- 0.7 versus 1.6+0.7, respectively). Diazoxide (10 mg/kg; s. c)
      significantly (p < 0.001) abolished the glybenclamide effect (1.6 +/- 0.8 versus
      14 +/- 1.2). CONCLUSIONS: The data indicate that the antinociceptive effect of
      sildenafil is dependent on the activation of the NO/cGMP/ K(ATP) pathway.

PMID- 17431747
TI  - Expression and characterization of the Na+/H+ exchanger in the mammalian
      myocardium.
AB  - We examined two expression systems for studying the Na(+)/H(+) exchanger in the
      mammalian myocardium. Mammalian NHE1 with a hemagglutinin (HA) tag and was cloned
      behind the alpha myosin heavy chain promoter. Transgenic mice were made with wild
      type NHE1 protein or with a hyperactive NHE1 protein mutated at the calmodulin
      binding domain. Three lines of transgenic mice were made of each cDNA with
      expression levels of each type varying from high to low. Higher levels and
      activity of the Na(+)/H(+) exchanger were associated with decreased long-term
      survival of mice, and with dilated or hypertrophic cardiomyopathy. The exogenous
      NHE1 protein was present in freshly made cardiomyocytes from transgenic mice,
      however, expression from the alpha myosin heavy chain promoter declined rapidly
      and little exogenous NHE1 was apparent on the fourth day after cardiomyocyte
      isolation. To express NHE1 protein in isolated cardiomyocytes, we transferred a
      mutated form of the protein into an adenoviral expression system. Infection of
      neonatal rat cardiomyocytes resulted in robust expression of the exogenous NHE1
      protein. The mutant form of the NHE1 protein could be distinguished from the
      endogenous Na(+)/H(+) exchanger by its resistance to inhibition by amiloride
      analogs. Our results suggest that for in vivo studies on intact hearts and
      animals, expression in transgenic mice is an appropriate system, however for long
      term studies on cardiomyocytes, this model is inappropriate due to waning
      expression from the alpha myosin heavy chain promoter. Therefore, infection by
      adenovirus is a superior system for long-term studies on cardiomyocytes in
      culture.

PMID- 17431748
TI  - Formation of bone-like apatite layer on chitosan fiber mesh scaffolds by a
      biomimetic spraying process.
AB  - Bone-like apatite coating of polymeric substrates by means of biomimetic process
      is a possible way to enhance the bone bonding ability of the materials. The
      created apatite layer is believed to have an ability to provide a favorable
      environment for osteoblasts or osteoprogenitor cells. The purpose of this study
      is to obtain bone-like apatite layer onto chitosan fiber mesh tissue engineering
      scaffolds, by means of using a simple biomimetic coating process and to determine
      the influence of this coating on osteoblastic cell responses. Chitosan fiber mesh
      scaffolds produced by a previously described wet spinning methodology were
      initially wet with a Bioglass((R))-water suspension by means of a spraying
      methodology and then immersed in a simulated body fluid (SBF) mimicking
      physiological conditions for one week. The formation of apatite layer was
      observed morphologically by scanning electron microscopy (SEM). As a result of
      the use of the novel spraying methodology, a fine coating could also be observed
      penetrating into the pores, that is clearly within the bulk of the scaffolds.
      Fourier Transform Infrared spectroscopy (FTIR-ATR), Electron Dispersive
      Spectroscopy (EDS) and X-ray diffraction (XRD) analysis also confirmed the
      presence of apatite-like layer. A human osteoblast-like cell line (SaOs-2) was
      used for the direct cell contact assays. After 2 weeks of culture, samples were
      observed under the SEM. When compared to the control samples (unmodified chitosan
      fiber mesh scaffolds) the cell population was found to be higher in the Ca-P
      biomimetic coated scaffolds, which indicates that the levels of cell
      proliferation on this kind of scaffolds could be enhanced. Furthermore, it was
      also observed that the cells seeded in the Ca-P coated scaffolds have a more
      spread and flat morphology, which reveals an improvement on the cell adhesion
      patterns, phenomena that are always important in processes such as
      osteoconduction.

PMID- 17431749
TI  - Isolation, identification, and quantification of potential defensive compounds in
      the viceroy butterfly and its larval host-plant, Carolina willow.
AB  - The viceroy-monarch and viceroy-queen butterfly associations are classic examples
      of mimicry. These relationships were originally classified as Batesian, or
      parasitic, but were later reclassified as Mullerian, or mutalistic, based on
      predator bioassays. The Mullerian reclassification implies that viceroy is
      unpalatable because it too is chemically defended like the queen and the monarch.
      However, unlike the queen and the monarch, the viceroy defensive chemistry has
      remained uncharacterized. We demonstrate that the viceroy butterfly (Limenitis
      archippus, Nymphalidae) not only sequesters nonvolatile defensive compounds from
      its larval host-plant, the Carolina willow (Salix caroliniana, Salicaceae), but
      also secretes volatile defensive compounds when disturbed. We developed liquid
      chromatography-mass spectrometry-mass spectrometry methods to identify a set of
      phenolic glycosides shared between the adult viceroy butterfly and the Carolina
      willow, and solid phase microextraction and gas chromatography-mass spectrometry
      methods to identify volatile phenolic compounds released from stressed viceroy
      butterflies. In both approaches, all structures were characterized based on their
      mass spectral fragmentation patterns and confirmed with authentic standards. The
      phenolics we found are known to deter predator attack in other prey systems,
      including other willow-feeding insect species. Because these compounds have a
      generalized defensive function at the concentrations we described, our results
      are consistent with the Mullerian reclassification put forth by other researchers
      based on bioassay results. It seems that the viceroy butterfly possesses chemical
      defenses different from its monarch and queen butterfly counterparts (phenolic
      glycosides vs. cardiac glycosides, respectively), an unusual phenomenon in
      mimicry warranting future study.

PMID- 17431750
TI  - Prevalence rates of gambling problems in Montreal, Canada: a look at old adults
      and the role of passion.
AB  - The purpose of the present research was to determine the prevalence rate of
      gambling problems in senior citizens (55 years and older). A community-dwelling
      sample composed of 810 old adults living in the greater Montreal area in the
      Province of Quebec completed the Revised South Oaks Gambling Screen (SOGS-R).
      Results revealed that the 12-month prevalence rate was 1.2% for pathological
      gambling and 1.6% for at-risk gambling. Although, these rates are comparable to
      those reported elsewhere in Canada and in the US for senior citizens, the at-risk
      gambling rate was significantly higher than the current one for the general
      population of the overall Province of Quebec. Finally, a smaller portion of
      participants also completed two key items from the Gambling Passion Scale (GPS).
      Results revealed that obsessive passion was higher for pathological gamblers than
      for at-risk and non-problematic gamblers, while harmonious passion was lower for
      pathological gamblers than for at-risk and non-problematic gamblers.

PMID- 17431751
TI  - Development of a physiology-based whole-body population model for assessing the
      influence of individual variability on the pharmacokinetics of drugs.
AB  - In clinical development stages, an a priori assessment of the sensitivity of the
      pharmacokinetic behavior with respect to physiological and anthropometric
      properties of human (sub-) populations is desirable. A physiology-based
      pharmacokinetic (PBPK) population model was developed that makes use of known
      distributions of physiological and anthropometric properties obtained from the
      literature for realistic populations. As input parameters, the simulation model
      requires race, gender, age, and two parameters out of body weight, height and
      body mass index. From this data, the parameters relevant for PBPK modeling such
      as organ volumes and blood flows are determined for each virtual individual. The
      resulting parameters were compared to those derived using a previously published
      model (P(3)M). Mean organ weights and blood flows were highly correlated between
      the two models, despite the different methods used to generate these parameters.
      The inter-individual variability differed greatly especially for organs with a
      log-normal weight distribution (such as fat and spleen). Two exemplary population
      pharmacokinetic simulations using ciprofloxacin and paclitaxel as model drugs
      showed good correlation to observed variability. A sensitivity analysis
      demonstrated that the physiological differences in the virtual individuals and
      intrinsic clearance variability were equally influential to the pharmacokinetic
      variability but were not additive. In conclusion, the new population model is
      well suited to assess the influence of individual physiological variability on
      the pharmacokinetics of drugs. It is expected that this new tool can be
      beneficially applied in the planning of clinical studies.

PMID- 17431753
TI  - Physiologically based pharmacokinetic (PBPK) modeling of everolimus (RAD001) in
      rats involving non-linear tissue uptake.
AB  - Everolimus is a novel macrolide immunosuppressant developed for the prophylaxis
      of allogeneic renal or cardiac transplant rejection. Treatments with
      immunosuppressants are often associated with organ toxicity that is linked to
      high organ exposure. Therefore, gaining insight into the pharmacokinetics of
      everolimus in various organs is highly desirable especially those organs of
      therapeutic interest or those that pose safety concerns. The aim of this work was
      to characterize the disposition kinetics of everolimus in rats by physiologically
      based pharmacokinetic (PBPK) modeling. Blood and tissue samples were collected
      from male Wistar rats over 24 hr following intravenous (iv) bolus and iv infusion
      of 1 mg/kg and 10 mg/kg/2 hr of everolimus. Further blood samples were collected
      between 1 and 170 hr from a third group of rats, which received iv infusion of 1
      mg/kg/2 hr of everolimus. Drug concentrations in blood and tissues were
      determined by a liquid chromatography reverse dilution method. Distribution of
      everolimus between blood fractions was determined in vitro at 37 degrees C. The
      results of the study demonstrated that everolimus exhibited moderate non-linear
      binding to red blood cells. Also, the tissue-to-blood concentration ratio
      decreased in all tissues as blood concentration increased. A PBPK model involving
      non-linear tissue binding was able to successfully describe the observed data in
      blood and all the organs investigated. The highest binding potential was observed
      in thymus, lungs, and spleen with the greatest tissue affinity observed in
      thymus, skin, and muscle as compared to other tissues. Everolimus exhibited a
      high clearance rate that was limited to the hepatic blood flow (47.2 ml/min/kg).
      The PBPK model was also able to predict the venous blood concentration reasonably
      well following oral administration. The oral bioavailability value, as estimated
      with the PBPK, was 12% and was similar to the value obtained by non-compartmental
      analysis. In conclusion, A PBPK model has been developed that successfully
      predicts the time course of everolimus in blood and a variety of organs. This
      model takes into account the non- linear binding of everolimus to red blood cells
      and tissues. This model may be used to predict everolimus concentration-time
      course in organs from other species including humans.

PMID- 17431755
TI  - Different genotypes of nephropathogenic infectious bronchitis viruses co
      circulating in chicken population in China.
AB  - Chicken nephropathogenic infectious bronchitis (IB) was prevalent in the most
      chicken farms during recent years, although the IB vaccination program has been
      widely performed in China. To characterize the S1 protein of infectious
      bronchitis virus (IBV) from China, five representative nephropathogenic IB
      viruses isolated from chickens in different provinces were genetically and
      phylogenetically analyzed. The results showed that the length of the S1 genes of
      the isolates were quite different (1,617, 1,620, 1,623, 1,629, and 1,632
      nucleotides, respectively). The homology of the nucleotides and amino acids among
      the five isolates were 76.7%-92.1% and 73.9%-89.5%, respectively, indicating a
      great variation in S1 genes of the isolates. The variation in S1 genes might
      affect the antigenicity and pathogenicity of the viruses. Genetically, point
      mutations, insertions, and deletions in the S1 protein can be observed at many
      positions, especially at the first 150 amino acids in the N-terminal of the S1
      protein. Two motif cleavage sites (R-R-X-R-R/S, H-R-R-R-R/S) were observed in the
      five sequenced strains. Phylogenetic analysis suggested that they belonged to
      different lineages. These findings indicated that different genotypes of
      nephropathogenic IB viruses were co-circulating in the chicken population in
      China.

PMID- 17431754
TI  - High Bcl-2/Bax ratio in Walker tumor cells protects mitochondria but does not
      prevent H2O2-induced apoptosis via calcineurin pathways.
AB  - It has been previously shown that Walker 256 tumor cells express a high content
      of the anti-apoptotic protein Bcl-2 which protects mitochondria against the
      damaging effects of Ca(2+). In the present study, we analyze H(2)O(2)-induced
      apoptotic death in two different types of tumor cells: Walker 256 and SCC-25.
      Treatment with H(2)O(2) (4mM) increased reactive oxygen species generation and
      the concentration of cytosolic free Ca(2+). These alterations preceded apoptosis
      in both cell lines. In Walker cells, which show a high Bcl-2/Bax ratio, apoptosis
      was dependent on calcineurin activation and independent of changes in
      mitochondrial membrane potential (DeltaPsi(m)), as well as cytochrome c release.
      In contrast, in SCC-25 cells, which show a lower Bcl-2/Bax ratio, apoptosis was
      preceded by a decrease in DeltaPsi(m), mitochondrial permeability transition, and
      cytochrome c release. Caspase-3 activation occurred in both cell lines. The data
      suggest that although the high Bcl-2/Bax ratio protected the mitochondria of
      Walker cells from oxidative stress, it was not sufficient to prevent apoptosis
      through calcineurin pathways.

PMID- 17431756
TI  - Barebacking, the Internet, and harm reduction: an intercept survey with gay and
      bisexual men in Los Angeles and New York City.
AB  - Researchers have suggested that intentional unprotected anal intercourse (UAI)
      among gay and bisexual men (colloquially called barebacking), is on the rise.
      Further, they have linked this increase in barebacking to the growth of the
      Internet as a medium for men to meet sex partners. Data were used from large
      scale gay, lesbian, and bisexual (GLB) community events in New York and Los
      Angeles collected between 2003 and 2004. In total 1178 men who have sex with men
      (MSM) responded to questions about the use of the Internet, willingness to have
      unplanned UAI, intentions toward planned UAI, and "barebacker identity." Compared
      to nonbarebackers, barebackers spent significantly more time on the Internet
      looking for sex and looking for dates. Further, HIV-positive barebackers
      specifically spent the most time online looking for dates. Further analyses of
      willingness and intentions to have UAI, and the specific sexual behaviors of self
      identified barebackers, found evidence of strategic positioning and serosorting,
      both harm reduction strategies. These data suggest both HIV-positive and HIV
      negative barebackers may be engaged in efforts to reduce the risk of HIV
      transmission when engaged in unprotected sex.

PMID- 17431757
TI  - Air bubble migration is a random event post embryo transfer.
AB  - INTRODUCTION: Air bubble location following embryo transfer (ET) is the
      presumable placement spot of embryos. The purpose of this study was to document
      endometrial air bubble position and migration following embryo transfer. DESIGN:
      Multicenter prospective case study. MATERIALS AND METHODS: Eighty-eight embryo
      transfers were performed under abdominal ultrasound guidance in two countries by
      two authors. A single or double air bubble was loaded with the embryos using a
      soft, coaxial, end opened catheters. The embryos were slowly injected 10-20 mm
      from the fundus. Air bubble position was recorded immediately, 30 minutes later
      and when the patient stood up. RESULTS: Bubble marker location analysis revealed
      a random distribution without visible gravity effect when the patients stood up.
      The bubble markers demonstrated splitting, moving in all directions and
      dispersion. CONCLUSION: Air bubbles move and split frequently post ET with the
      patient in the horizontal position, suggestive of active uterine contractions.
      Bubble migration analysis supports a rather random movement of the bubbles and
      possibly the embryos. Standing up changed somewhat bubble configuration and
      distribution in the uterine cavity. Gravity related bubble motion was uncommon,
      suggesting that horizontal rest post ET may not be necessary. This report
      challenges the common belief that a very accurate ultrasound guided embryo
      placement is mandatory. The very random bubble movement observed in this two
      center study suggests that a large "window" of embryo placement maybe present.

PMID- 17431758
TI  - Developing operating principles for systems change.
AB  - Based on an analysis of the articles in this special issue, the authors propose
      five operating principles for systems change work. These principles are:
      clarifying the purpose of the systems change; identifying whether the change is
      one to an existing system or the change is to create a new system; conceptualize
      the work as systems change from the beginning; use an eclectic approach; and be
      open to opportunities that emerge while also undertaking forma analysis to
      identify leverage points. The authors argue that the time is now ripe to develop
      such principles and encourage community change agents to engage in a dialogue to
      explore, revise, eliminate or expand on these principles.

PMID- 17431759
TI  - Advanced stages and poorly differentiated grade are associated with an increased
      risk of HER2/neu positive breast carcinoma only in White women: findings from a
      prospective cohort study of African-American and White-American women.
AB  - OBJECTIVE: The primary objective of this study was to evaluate the race-specific
      risk associated with HER2/neu positive breast carcinoma in a prospective cohort
      design. Our secondary objectives were to assess prevalence of different breast
      cancer phenotypes between African-American and White women and to determine if
      race was associated with the risk of basal-like breast carcinoma phenotype in
      this cohort. METHODS: Demographic, clinical and pathologic data were collected
      from existing databases. The status of HER2/neu and hormone receptors was
      dichotomized as either positive or negative. Immunohistochemistry taxonomy was
      used to assess prevalence of different breast carcinoma phenotypes. Risk
      estimates were calculated using the multivariable logistic regression statistics.
      CONCLUSIONS: The risk of HER2/neu positive breast carcinoma differs between
      African-American and White women. For White women only, this risk was
      statistically significant and increased almost linearly within each TNM stage
      with grade dedifferentiation. The statistically significantly higher prevalence
      of "ER(-)/PR(-), HER2(- )" phenotype in African American women potentially is the
      attributing factor to observed lack of an association between the risk of
      HER2/neu positive breast carcinoma with advanced stages and poorly differentiated
      grade. Among women diagnosed with "ER(-)/PR(-), HER2(-)" phenotype the odds
      ratios of being African-American and pre-menopausal was 1.72 (95% CI 1.17-2.54, P
      = 0.006) and 1.94 (95% CI 1.27-2.96, P = 0.002), respectively. The histologic
      features of basal-like and ER(-)/HER2(+ )carcinomas overlaps. Differences in the
      biology of breast carcinoma between African American and White women are
      partially attributed to the disparity in more adverse pathologic prognostic
      indicators at the initial clinical presentation of this disease.

PMID- 17431760
TI  - Hormone replacement therapy, mammography screening and changing age-specific
      incidence rates of breast cancer: an ecological study comparing two European
      populations.
AB  - BACKGROUND: In 2003, for the first time, US breast cancer incidence rates have
      fallen. Experts argue whether this is due to the reduced uptake of screening
      mammography or to lower use of Hormone Replacement Therapy (HRT). This study aims
      to disentangle the respective impact of screening and HRT on age-incidence rates
      and histology of breast cancer, by comparing two populations with comparably high
      levels of screening mammography, but with different prevalence of HRT. METHODS:
      We included all invasive breast cancers recorded at the Geneva cancer registry (n
      = 4,909) and the Netherlands Cancer Registry (n = 152,428) between 1989-2003. We
      compared age-specific incidence rates and trends in histological subtyping
      between the two populations. RESULTS: Between 1989-1991, incidence rates
      increased with age in both populations. In 2001-2003, women aged 60-64 years
      showed highest incidence rates in Geneva, while in the Netherlands incidence
      rates continued to increase with age. The annual increase in ductal cancer
      incidence was similar in the Netherlands (2.3%) and Geneva (2.5%), but the annual
      increase in lobular cancer was sharper in Geneva (10%) than in the Netherlands
      (5%). CONCLUSION: The sharp differences in age distribution and histological
      subtyping of breast cancer between two European populations are not attributable
      to screening, since both populations have a high uptake of mammography screening.
      Since the prevalence of HRT use is very high in Geneva and rather low in the
      Netherlands, HRT may explain these discrepancies. However, other etiological
      factors and differences in histological assessment may also have played a role.

PMID- 17431761
TI  - Diminished feedback regulation of proteasome expression and resistance to
      proteasome inhibitors in breast cancer cells.
AB  - Clinical trials with proteasome inhibitor Bortezomib (also named Velcade or PS
      341) has shown promising results for some cancers. However, other types of
      cancers including breast cancer do not respond well to Bortezomib. To understand
      the cause of the drug resistance, we compared the regulation of proteasome
      expression and the sensitivity to proteasome inhibitors between human breast
      cancer cells and nontumorigenic mammary epithelial cells. We found that, while
      the endogenous expression level is much higher, the potential of feedback
      expression in response to proteasome inhibitors is much lower in the breast
      cancer cells. Furthermore, the breast cancer cells are much more resistant to
      proteasome inhibitors compared to the nontumorigenic mammary epithelial cells.
      Biochemical analysis showed that the pathway of Bortezomib-induced apoptosis is
      apparently defective in the breast cancer cells. Together, these results provide
      an explanation for the inefficacy of Bortezomib in the clinical trials for breast
      cancer patients. The likelihood of combination therapy with Bortezomib and other
      anti-cancer agents for breast cancer is also discussed.

PMID- 17431762
TI  - Stromal mast cells in invasive breast cancer are a marker of favourable
      prognosis: a study of 4,444 cases.
AB  - PURPOSE: We have previously demonstrated in a pilot study of 348 invasive breast
      cancers that mast cell (MC) infiltrates within primary breast cancers are
      associated with a good prognosis. Our aim was to verify this finding in a larger
      cohort of invasive breast cancer patients and examine the relationship between
      the presence of MCs and other clinical and pathological features. EXPERIMENTAL
      DESIGN: Clinically annotated tissue microarrays (TMAs) containing 4,444 cases
      were constructed and stained with c-Kit (CD-117) using standard immunoperoxidase
      techniques to identify and quantify MCs. For statistical analysis, we applied a
      split-sample validation technique. Breast cancer specific survival was analyzed
      by Kaplan-Meier [KM] method and log rank test was used to compare survival
      curves. RESULTS: Survival analysis by KM method showed that the presence of
      stromal MCs was a favourable prognostic factor in the training set (P = 0.001),
      and the validation set group (P = 0.006). X-tile plot generated to define the
      optimal number of MCs showed that the presence of any number of stromal MCs
      predicted good prognosis. Multivariate analysis showed that the MC effect in the
      training set (Hazard ratio [HR] = 0.804, 95% Confidence interval [CI], 0.653
      0.991, P = 0.041) and validation set analysis (HR = 0.846, 95% CI, 0.683-1.049, P
      = 0.128) was independent of age, tumor grade, tumor size, lymph node, ER and Her2
      status. CONCLUSIONS: This study concludes that stromal MC infiltration in
      invasive breast cancer is an independent good prognostic marker and reiterates
      the critical role of local inflammatory responses in breast cancer progression.

PMID- 17431763
TI  - Prophylactic IL-12 treatment reduces postoperative metastasis: mediation by
      increased numbers but not cytotoxicity of NK cells.
AB  - Despite a promising potential, interleukin-12 immunotherapy has yielded limited
      clinical success while causing perilous toxicities. Here we study a context in
      which IL-12 may prove clinically beneficial--the removal of the primary tumor,
      when cell-mediated immunity (CMI) may eradicate minimal residual disease (MRD),
      but is inhibited by postoperative immunosuppression, potentially leading to
      enhanced malignant progression. F344 rats were preoperatively treated with IL-12
      and inoculated postoperatively with syngeneic MADB106 tumor cells. An optimal
      regimen of eight-day sustained exposure to IL-12 was developed (1
      microg/rat/day), which caused mild side effects, increased baseline resistance to
      experimental MADB106 metastasis, and abolished the promotion of metastasis by
      laparotomy and other immunosuppressive paradigms. Depletion of NK cells indicated
      their major role in controlling MADB106 metastasis in naive and IL-12 treated
      rats. Studying NK cytotoxicity, we found that IL-12 did not potentiate activity
      per NK cell, nor protected it from suppression by surgery. However, IL-12
      increased the numbers of NK cells in the circulation and marginating pulmonary
      pool of naive and operated rats, and correspondingly increased total NK activity
      in these compartments. Therefore, this study indicates anti-tumor effects of IL
      12 based on increased numbers of strategically located NK cells, and advocates a
      prophylactic approach against the potential metastasis-promoting effects of
      surgery.

PMID- 17431764
TI  - Dietary animal-derived iron and fat intake and breast cancer risk in the Shanghai
      Breast Cancer Study.
AB  - BACKGROUND: Dietary fats and other constituents have been studied extensively in
      relation to breast cancer risk. Iron, an essential micronutrient with pro-oxidant
      properties, has received little attention, and specific fats may augment its
      toxicity. We investigated the effects of iron and fats from various food sources
      on the risk of breast cancer. METHODS: Participants in a population-based case
      control study, 3,452 breast cancer cases, and 3,474 age-frequency-matched
      controls, completed in-person interviews, including a detailed food-frequency
      questionnaire. Plant- and animal-derived iron and fat intakes were derived from
      dietary intake data and food composition tables. Unconditional logistic
      regression models were used to study the independent and interactive effects of
      different forms of iron and fats on breast cancer risk. RESULTS: Animal-derived
      (largely heme) iron intake was positively associated with breast cancer risk (P
      (trend) < 0.01; OR = 1.49 in the highest vs. lowest quartile, 95% confidence
      interval [CI] 1.25-1.78) after adjustment for known risk factors, antioxidant
      vitamin and isoflavone intake, and vitamin supplement use. The effect of animal
      derived iron was similar in pre- and postmenopausal women. Intake of animal
      derived fats was also associated with increased risk (adjusted OR = 1.34, 95% CI
      1.14-1.58), particularly after menopause. A significant interaction between iron
      and fat from animal sources was observed (P < 0.01). CONCLUSIONS: A high intake
      of animal-derived (heme) iron may be associated with an increased risk of primary
      breast cancer in Chinese women, and saturated and mono-unsaturated fats that are
      also derived from animal sources may augment this effect. Combined reductions in
      animal-derived iron and fat consumption have the potential to reduce breast
      cancer risk.

PMID- 17431765
TI  - Prophylactic mastectomy in familial breast carcinoma. What do the pathologic
      findings learn us?
AB  - OBJECTIVE: To evaluate the indications, techniques and pathologic findings of
      prophylactic mastectomy (pME). METHODS: Retrospective study of patients with a
      strong family history of breast cancer (and ovarian cancer) or with proven BRCA
      mutation. RESULTS: Between January 1995 and December 2005, sixty seven patients
      underwent pME: 15% had a BRCA1 mutation, 31% had a BRCA2 mutation and 33% had a
      strong family history but without proven BRCA mutation and in 21% mutation
      analysis was not performed. Fifty eight percent had a personal history of breast
      cancer of which 84% previously underwent a unilateral mastectomy as part of their
      treatment. The median time to decision from previous treatment for breast
      carcinoma to pME was 46 months. Mean age at pME was 43 years. Pathologic
      examination of the pME specimens revealed invasive and/or in situ carcinoma in
      19% (13/67). Atypical ductal/lobular hyperplasia (ADH/ALH) or flat epithelial
      atypia (FEA) were present in another 3%. CONCLUSION: Twenty two percent of women
      at high risk for breast cancer presented at the time of pME with invasive
      carcinoma or intra-epithelial neoplasia undetected by imaging and clinical
      examination.

PMID- 17431766
TI  - Two-stage case-control study of common ATM gene variants in relation to breast
      cancer risk.
AB  - The ataxia telangiectasia mutated (ATM) gene is a tumor suppressor gene that
      plays a critical role in cell cycle arrest, apoptosis, and DNA repair. We
      evaluated two reported nonsynonymous SNPs (rs1800054 and rs1800058) and three
      additional common gene variants (rs664143, rs228589, rs1003623) in the ATM gene
      in relation to breast cancer risk. A two-stage case-control study, using data
      from the Shanghai Breast Cancer Study, was conducted in which all SNPs were
      screened in the stage I study, including 1,123 cases and 1,232 controls. Any
      promising associations were re-evaluated in the stage II study, including 2,003
      cases and 1,918 controls. In the stage I study, with the exception of rs1003623,
      no apparent association was found for any other SNPs with breast cancer risk. For
      the rs1003623, the T allele was associated with an increased breast cancer risk
      among postmenopausal women with odds ratios (ORs) of 1.4 (95% Confidence
      Intervals (CIs) = 1.0-1.9) for the CT and 1.6 (95% CIs = 1.0-2.4) for the TT, (P
      for trend = 0.03). This association, however, was not replicated in the stage II
      study, suggesting that the positive association identified in stage I for
      rs1003623 may be due to chance. Our study reveals no apparent association of
      common ATM variants with breast cancer risk and underscores the importance of
      replication using independent samples to reduce type I errors in association
      studies of low-penetrance genetic factors.

PMID- 17431767
TI  - Does risk equalization reduce the viability of voluntary deductibles?
AB  - Theoretically, a risk avers consumer takes a deductible if the premium rebate
      (far) exceeds his/her expected out-of-pocket expenditures. In the absence of risk
      equalization, insurers are able to offer high rebates because those who select
      into a deductible plan have below-average expenses. This paper shows that, for
      high deductibles, such rebates cannot be offered if risk equalization would
      "perfectly" adjust for the effect of self selection. Since the main goal of user
      charges is to reduce moral hazard, some effect of self selection on the premium
      rebate can be justified to increase the viability of voluntary deductibles.

PMID- 17431769
TI  - Quercetin prevents oxidative stress in cirrhotic rats.
AB  - Our aim was to study the protective effect of quercitin on liver cirrhosis
      induced by carbon tetrachloride (CCl(4)) in rats and its relationship with liver
      morphology. Thirty male Wistar rats weighing 200-250 g were randomly divided into
      three groups: control, CCl(4), and CCl(4)+ quercetin. Rats in the experimental
      groups were given CCl(4) (0.5 ml/kg i.p.), diluted 1:6 in vegetable oil (5
      mmol/kg body wt), at 10:00 p.m. every 4 days for 17 weeks. Quercetin (500
      microl/kg i.p.; 150 micromol/kg body wt) or vehicle was administered at 6:00 p.m.
      for the last 3 weeks of the study. Control group rats were given only olive oil
      for the same period. At the end of the 17 weeks, all rats were sacrificed. Blood
      samples were taken for determination of serum indicators (ALT, AST, total
      bilirubin, conjugated bilirubin, factor V) and the livers were dissected out and
      divided into two parts: one was homogenized and the supernatant was used for
      measurement of superoxide dismutase (SOD), catalase, and glutathione peroxidase
      (GPx) activities, as well as lipid peroxidation. The other part was used for the
      histopathological study. CCl(4) caused a marked rise in serum levels of ALT, AST,
      total bilirubin, and conjugated bilirubin, as well as a decrease in factor V
      (P<0.05). Lipid peroxidation levels were significantly increased, whereas GSH,
      SOD, catalase, GPx, and GST levels were decreased in the liver of CCl(4)-treated
      rats. Quercetin (50 mg/kg/day) successfully attenuated these effects of CCl(4).
      We conclude that quercetin has beneficial effects on liver fibrosis in rats by
      enhancing antioxidant enzyme activity and decreasing the pro-oxidant effect.

PMID- 17431768
TI  - Erdosteine prevents colonic inflammation through its antioxidant and free radical
      scavenging activities.
AB  - After intracolonic administration of trinitrobenzene sulphonic acid (TNBS),
      Sprague-Dawley rats were treated orally either with saline or erdosteine (100
      mg/kg per day), a sulfhydryl-containing antioxidant, for 3 days. On the 4th day,
      rats were decapitated and distal colon was removed for the macroscopic and
      microscopic damage scoring, for the measurement of malondialdehyde (MDA),
      glutathione (GSH) and collagen levels, myeloperoxidase (MPO) activity, luminol
      and lucigenin chemiluminescence (CL) and DNA fragmentation. Lactate dehydrogenase
      (LDH) activity, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and
      antioxidant capacity were assayed in blood samples. Colitis caused significant
      increases in the colonic CL values, macroscopic and microscopic damage scores,
      MDA and collagen levels, MPO activity and DNA fragmentation, along with a
      significant decrease in tissue GSH level. Similarly, serum cytokines and LDH were
      elevated in the saline-treated colitis group as compared with the control group.
      On the other hand, erdosteine treatment reversed all these biochemical indices,
      and histopathologic alterations induced by TNBS, suggesting that erdosteine
      protects the colonic tissue via its radical scavenging and antioxidant
      activities.

PMID- 17431770
TI  - Abdominal pain after colonoscopy: can it be acute cholecystitis?

PMID- 17431771
TI  - Colonic manometry catheter placement with primary fluoroscopic guidance.
AB  - The purpose of this paper is to describe our experience with a new technique of
      colonic manometry catheter placement using fluoroscopic guidance. Between 2000
      and 2004, 44 colonic manometry catheters were placed with primary fluoroscopic
      guidance in 38 patients (25 males; median age, 7 years; range, 0.4-31 years) with
      severe defecation disorders. Fourteen colonoscopic placements were reviewed to
      compare the different procedures. Manometry catheters were inserted through the
      rectum (16 patients), cecostomy (9), ileostomy (2), and colostomy (17).
      Placements through diverted colons were successful in 24 of 28 (86%). Insertion
      through the rectum was successful in 10 of 16 (63%) fluoroscopic-guided
      placements vs. 12 of 14 (86%) colonoscopic placements (P=0.23). Significantly
      longer fluoroscopic exposure was required for fluoroscopic compared to
      colonoscopic placement (P=0.004). In conclusion, placement of colonic manometry
      catheters with primary fluoroscopic guidance is feasible in children. An
      important disadvantage of the fluoroscopic methodology is the prolonged
      fluoroscopic exposure time.

PMID- 17431772
TI  - Pharmacokinetics of cyclosporine A after massive hepatectomy: a hint for small
      for-size graft in living donor liver transplantation.
AB  - In living donor liver transplantation, graft size is very important, and various
      studies have been conducted regarding these problems in small-for-size (SFS)
      grafts. The administration of immunosuppressants for SFS graft, in which the
      functional liver mass is small and necessary for excessive liver regeneration,
      has not been reported so far. The aims of this study were to investigate the
      optimal administration of cyclosporine (CyA) and characteristics of metabolism of
      CyA, according to liver volume. Seven-week-old male Wister rats were randomly
      divided into four groups: two CyA-administered groups (CyA groups), 70% and 90%
      hepatectomy (Hx); and two control groups, 70% and 90% Hx. The 70% Hx and 90% Hx
      were used as the surrogate model of SFS for 30% and 10% graft models. In CyA
      groups, CyA (5 mg/kg/day) was given for 3 days before Hx and after surgery until
      sacrifice. Animals were sacrificed at 0, 12, 24, 48, and 72 hr after Hx. The
      blood concentration of CyA and the expression of the CYP3A2 gene were measured at
      each point in CyA groups, and liver regeneration was evaluated by measuring the
      ratio of remnant liver weight to body weight in each group. Regarding the blood
      concentration of CyA, no difference was recognized between 30% and 10% graft
      models except for 72 hr after Hx. As for liver regeneration, no significant
      difference was recognized. Regarding the expression of CYP3A2, no change was
      noted in the 30% graft model; on the other hand, CYP3A2 expression was reduced.
      Significant differences between the 30% and the 10% graft model were observed 48
      and 72 hr after Hx. The blood concentration of CyA was not dependent on the
      volume of the liver graft.

PMID- 17431773
TI  - Rotavirus causes hepatic transaminase elevation.
AB  - Rotavirus is one of the leading causes of acute gastroenteritis among children.
      While clinical complaints are generally intestinal including vomiting and
      diarrhea, there is evidence to suggest that disease outside the gastrointestinal
      tract occurs. This study examines the frequency of hepatic transaminase elevation
      in children with rotavirus gastroenteritis. Patients identified with rotavirus
      gastroenteritis by stool antigen testing between November 2005 and March 2006 had
      available serum analyzed for alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), alkaline phosphatase, total bilirubin, direct bilirubin,
      and creatinine phoshosphokinase (CPK). Chart review was conducted to identify
      patients with possible liver injury unrelated to rotavirus. Among the 92 patients
      identified with rotavirus during the study period, 75 had serum specimens
      available for testing. Fifteen patients (20%) had elevated ALT and AST, including
      one patient with an increase in AST, ALT, alkaline phosphatase, and total and
      direct bilirubin. The mean ALT elevation was 56 IU/L (range, 44 to 114 IU/L), and
      the mean AST elevation was 80 IU/L (range, 57 to 126 IU/L). Fifty-three patients
      (71%) had an increase in AST alone, and three patients (4%) had an increase in
      AST and alkaline phosphatase. The mean AST values in these groups were 61 IU/L
      (range, 42 to 110 IU/L) and 79 IU/L (range, 59 to 96 IU/L), respectively. In
      conclusion, rotavirus commonly causes elevation of liver transaminases.

PMID- 17431774
TI  - Apolipoprotein E gene polymorphism in nonalcoholic fatty liver disease.
AB  - The aim of this study was to evaluate the relationship between apolipoprotein E
      gene polymorphism and nonalcoholic fatty liver disease. The study group consisted
      of 237 nonalcoholic fatty liver disease patients who were detected by
      ultrasonography and 201 controls with ultrasonographically normal livers. DNA
      amplifications were performed by polymerase chain reaction technique and
      apolipoprotein E genotypes were evaluated after digestion with CfoI restriction
      enzyme. Serum levels of glucose, lipids, lipoproteins, and apolipoproteins were
      measured in all subjects. Additionally, viral hepatitis markers, liver enzymes,
      and body mass index were assessed. Patients were found to have significantly
      higher triglyceride, glucose, aspartate aminotransferase, alanine
      aminotransferase, and gamma-glutamyltransferase levels and lower high-density
      lipoprotein cholesterol and apolipoprotein (a) levels than controls (P<0.05).
      There were no statistically significant differences in genotypes and allele
      frequencies between all patients and controls. Comparing nonobese patients with
      controls, the frequencies of allele epsilon2 and genotype epsilon2epsilon3 were
      statistically significantly different in the controls (P=0.04 and P=0.01,
      respectively). In conclusion, occurrence of the epsilon2 allele and
      epsilon2epsilon3 genotype may be protective against development of nonalcoholic
      fatty liver disease.

PMID- 17431775
TI  - Gastrointestinal manifestations in patients with common variable
      immunodeficiency.
AB  - This study focuses on endoscopic and pathologic alterations of gastrointestinal
      (GI) disorders of Iranian patients with common variable immunodeficiency (CVID).
      Nineteen of 39 CVID patients (48%) had GI complaints. The most common symptom was
      chronic diarrhea (28%). In endoscopic examination of small intestines, 15
      patients had no abnormal finding. Duodenal biopsy revealed villous atrophy in
      eight and nodular lymphoid hyperplasia in three patients. There was no
      statistically significant difference between patients with and patients without
      duodenal villous atrophy regarding the presence of chronic diarrhea, anemia, and
      absolute CD4+T cells. In three patients, biopsies of the colon showed chronic
      noncrypt-destructive colitis. GI problems pose a high morbidity to CVID patients
      and are second only to respiratory complications. CVID patients are at increased
      risk of infectious and inflammatory conditions in the GI tract. Early diagnosis
      of these complications improves the quality of life and well-being of patients.

PMID- 17431776
TI  - Vitiligo improvement in a hepatitis C patient after treatment with PEG-interferon
      alpha-2a and ribavirin: a case report.

PMID- 17431777
TI  - Adefovir dipivoxil alone or in combination with lamivudine for three months in
      patients with lamivudine resistant compensated chronic hepatitis B.
AB  - We studied clinical and laboratory effects of 3 months of lamivudine with
      adefovir combination and adefovir dipivoxil (AD) alone in the treatment of
      patients with lamivudine-resistant hepatitis B virus (HBV) infection. Eligible
      patients were hepatitis B surface antigen-positive men and women with compensated
      liver disease who were given lamivudine at least more than 6 months and had HBV
      polymerase gene mutation. Patients were assigned to receive adefovir 10 mg/day
      (Group 1) or adefovir 10 mg once daily and lamivudine 100 mg once daily
      combination during first 3 months, and then stopped lamivudine and continued
      adefovir (Group 2). Median age was 48 years (34 males and 20 females, and 35 were
      HBeAg-negative). Baseline median ALT, AST, and HBV DNA levels were 66 IU/l, 49
      IU/l, and 6.7 log(10) copy/ml, respectively. Median adefovir therapy time and ALT
      normalization time were 9 and 3.5 months, respectively. There was no significant
      difference between groups according to the baseline HBV DNA, ALT, HBe Ag status,
      age, gender, and lamivudine resistance time. Virological and biochemical
      responses were similar in both groups during therapy. Two patients (8%) had ALT
      flare more than five times upper limit of normal without any clinical
      decompensation in Group 1. Mild ALT elevation according to baseline levels were
      found in 8 (27.6%) and 4 (17.4%) patients, respectively, in Group 2 and Group 1,
      and no statistically significance between two groups. In conclusion, this study
      showed that it is not necessary to continue lamivudine therapy while switching to
      AD therapy. Adefovir alone is effective in the treatment of patients with
      lamivudine resistant HBV infection and compensated liver disease, without
      significant clinical and laboratory flares. However, it is not easy to say that
      switching to AD with cessation of lamivudine is safe, because the study
      population is not enough for precise conclusion and resistance may be a
      considerable problem against AD in patients using long-term treatment.

PMID- 17431778
TI  - Reactivation versus primary CMV infection after splenectomy in immunocompetent
      patients.
AB  - Acute CMV infection in the immunocompetent host is usually asymptomatic or
      produces only mild symptoms. CMV infection in immunocompromized patients,
      especially transplant recipients and those infected with HIV, is a result of
      profound lymphopenia or dysfunction of CD4+/CD8+ cells and can cause substantial
      rates of complication and death. We present a case of CMV infection in a
      previously healthy man who just had splenectomy for blunt trauma: a short
      incubation of the CMV disease, a strongly positive CMV antigenemia, severity of
      the disease including prominent lymphocytosis, massive hepatic sinusoidal
      infiltration, and retinitis. Splenectomy changed the immunological defense
      against the virus and brought the infection to nearly fulminant scale.

PMID- 17431779
TI  - Helicobacter pylori stool antigen assay in hyperemesis gravidarum: a risk factor
      for hyperemesis gravidarum or not?
AB  - OBJECTIVE: To test the hypothesis that Helicobacter pylori (H. pylori) infection
      may cause hyperemesis gravidarum (HG). MATERIALS AND METHODS: A prospective
      comparative study was performed on 107 pregnant patients from October 2002 to
      December 2003 in a university-based prenatal care clinic. Blood and stool samples
      were obtained from 52 patients diagnosed as HG and 55 matched asymptomatic
      pregnant women. H. pylori stool antigen (HpSA) status of the participants was
      evaluated using a commercially available enzyme immunoassay-based kit. RESULTS:
      The overall prevalence of HpSA positivity appeared as 41.1%. Twenty-two of 52
      (42.3%) HG patients and 22 of 55 (40.0%) control subjects were positive for HpSA.
      The difference was not significant (p>.05). CONCLUSION: HG seemed to be not
      associated with H. pylori infection, as indicated by specific stool antigen
      assay.

PMID- 17431780
TI  - New type of artificial liver support system (ALSS) using the photocatalytic
      effect of titanium oxide.
AB  - Although various types of artificial liver support systems (ALSSs) including a
      hybrid type have been made, few are practical ALSSs for treatment of acute and/or
      chronic hepatic failure. Titanium oxide (TiO(2)), a stable material, dismantles
      various materials using a photocatalytic action under ultraviolet irradiation.
      The aim of this study was to assess the effect of a new ALSS using TiO(2).
      Hepatic failure plasma obtained from patients undergoing plasma exchange therapy
      due to acute liver failure was used in these experiments. The plasma was perfused
      using a closed circuit model with a column filled with TiO(2). The plasma
      concentrations of total bilirubin, albumin, fibrinogen, interleukin (IL)-6, IL-8,
      and IL-10 were serially measured. We evaluated the photocatalytic effect of
      TiO(2) irradiated with ultraviolet light. The effect of initial perfusion with
      fresh-frozen plasma (FFP) was also investigated, focusing on the decrease in
      fibrinogen during perfusion. Levels of total bilirubin decreased after perfusion
      using the column filled with TiO(2), compared with no UV irradiation. The levels
      of IL-6, IL-8, and IL-10 decreased after perfusion using the TiO(2) device. The
      albumin level was maintained at the initial level, however, the fibrinogen level
      decreased within 4 hr. Initial perfusion of the circuit with FFP improved the
      decrease in fibrinogen for up to 8 hr. Our new perfusion device using the
      photocatalytic action of TiO(2) may be a promising ALSS.

PMID- 17431782
TI  - Effects of motilin and mitemcinal (GM-611) on gastrointestinal contractile
      activity in rhesus monkeys in vivo and in vitro.
AB  - Neither the presence of motilin receptors nor their action has been investigated
      in monkeys. The object of this study was to determine the effects of motilin and
      mitemcinal (GM-611), an erythromycin derivative, on the gastrointestinal tract in
      rhesus monkeys in vivo and in vitro. In in vivo investigations in conscious
      monkeys, both motilin and mitemcinal induced migrating motor complex-like
      contractions in the interdigestive state and also accelerated gastric emptying.
      In in vitro investigations, the presence of motilin receptors in the
      gastrointestinal tract was demonstrated by receptor binding assays. Motilin and
      mitemcinal contracted isolated duodenum strips in a concentration-dependent
      manner. In conclusion, rhesus monkeys may be useful for studying the
      physiological and pharmacological roles of the motilin agonistic mechanism
      because they show reactivity to motilin both in vivo and in vitro.

PMID- 17431781
TI  - Incidence, diagnosis, and therapy of cholangiocarcinoma in patients with primary
      sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PSC) can lead to the development of
      cholangiocarcinoma (CCA). The tumor may present as an intrahepatic focal
      cholangiocellular carcinoma but more often as a ductal infiltrating desmoplastic
      lesion. CCA is found synchronously with the diagnosis of PSC in 20-30% and within
      1 year in 50%. During later follow-up, the yearly developmental rate of CCA is
      0.5-1.5%. Most patients with PSC and CCA do not yet have cirrhosis but present
      with a severe stenosis at the hilum of the liver. This type of tumor is difficult
      to diagnose by imaging techniques.(18)F-FDG-PET scanning and CEA or CA 19-9 are
      not early diagnostic tools. Regular MRI, multislice CT, and repeated
      endoscopically obtained brush cytology of stenotic lesions are recommended. The
      recent use of more extensive surgical resection techniques in patients with CCA
      results in 5-year survival rates of > or =50%. If tumors are small or incidental
      findings, liver transplantation leads to a 3- to 5-year survival rate of 35%.
      Pretransplant radiotherapy with 5-FU chemosensitization followed by endoscopic
      brachytherapy with iridium-192 seems to greatly improve the outcome of
      transplantation. Treatment with ursodeoxycholic acid may prevent development of
      CCA.

PMID- 17431783
TI  - Betel nut use among first and second generation Bangladeshi women in London, UK.
AB  - This study evaluated the effects of socio-economic variables and migration
      history on the prevalence of betel nut and smokeless tobacco use in both UK- and
      Bangladeshi born migrant women resident in London. No significant difference in
      betel nut use prevalence was found among women of different generations. However,
      in all groups betel nut users were significantly older and less educated than non
      users. Among first generation women there was no effect of either length of time
      living in the UK or age at migration on use of betel nut, even after controlling
      for current age. No significant differences in prevalence use due to language
      spoken, occupation, marital status or borough of residence in London were found.
      We conclude that, although there are some indications of a change in behavior
      among younger individuals, betel nut chewing is a practice very much present
      among Bangladeshi women born and brought up in a bicultural context.

PMID- 17431784
TI  - Medical pluralism of Chinese women living in the United States.
AB  - This study provides national prevalence estimates for complementary and
      alternative (CAM) use, visits to doctors for health problems, and the effects of
      acculturation on health practices in Chinese women living in the United States. A
      national telephone survey of 3,172 women on their use of complementary and
      alternative medicine was conducted in 2001. This study focuses on a subsample of
      804 Chinese-American women who were asked about health practices and service
      utilization. Interviews were conducted in Mandarin, Cantonese and English. Forty
      one percent of Chinese-American women used some form of CAM in 2001. Socio
      economic status, a common predictor of CAM use in other studies of the general
      population in the United States, did not predict use in this sample. Traditional
      Chinese medicine (TCM) is used across acculturation levels. As Chinese women
      adapt to American culture they tend to use a greater variety of healthcare
      practices and to adopt mainstream CAM practices, but they also continue to use
      TCM.

PMID- 17431786
TI  - Complimentary endothelial cell/smooth muscle cell co-culture systems with
      alternate smooth muscle cell phenotypes.
AB  - Development of in vitro models of native and injured vasculature is crucial for
      better understanding altered wound healing in disease, device implantation, or
      tissue engineering. Conditions were optimized using polyethyleneteraphalate
      transwell filters for human aortic endothelial cell (HAEC)/smooth muscle cell
      (HASMC) co-cultures with divergent HASMC phenotypes ('more or less secretory')
      while maintaining quiescent HAECs. Resulting HASMC phenotype was studied at 48
      and 72 h following co-culture initiation, and compared to serum and growth factor
      starved monocultured 'forced contractile' HASMCs. Forced contractile HASMCs
      demonstrated organized alpha-smooth muscle actin filaments, minimal interleukin-8
      (IL-8) and monocyte chemotactic protein-1 (MCP-1) secretion, and low
      intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule
      1 (VCAM-1), and tissue factor expression. Organization of alpha-smooth muscle
      actin was lost in 'more secretory' HASMCs in co-culture with HAECs, and IL-8 and
      MCP-1 secretion, as well as ICAM-1, VCAM-1, and tissue factor expression were
      significantly upregulated at both time points. Alternately, 'less secretory'
      HASMCs in co-culture with HAECs showed similar characteristics to forced
      contractile HASMCs at the 48 h time point, while by the 72 h time point they
      behaved similarly to 'more secretory' HASMCs. These co-culture systems could be
      useful in better understanding vascular healing, however there remain time
      constraint considerations for maintaining culture integrity/cell phenotype.

PMID- 17431785
TI  - Breast cancer among immigrants: a systematic review and new research directions.
AB  - This paper highlights the relationship between migration and female breast
      cancer. A comprehensive review aimed at identifying risk and protective factors
      that cut across races and ethnicities was performed. A total of 79 studies (1971
      2005) from 16 countries were reviewed. The findings are consistent with existing
      knowledge about the importance of potentially modifiable environmental and
      behavioral determinants of risk, acting both pre- and post-migration. While the
      acculturation-based risk transition model is strong, it is not always supported.
      As a new direction for migrant studies, we extrapolate the review findings to the
      experience of Eastern European (EE) immigrants. Health data on this population,
      typically characterized by low health motivation and passive receipt of
      preventive efforts, are largely unavailable. Based on relevant theory, empirical
      and qualitative studies, two breast cancer prevention models for the EE immigrant
      population are proposed and the need for future research using ethnically
      disaggregated data is discussed.

PMID- 17431787
TI  - Methods for three-dimensional geometric characterization of the arterial
      vasculature.
AB  - Complex vascular anatomy often affects endovascular procedural outcome. Accurate
      quantitative assessment of three-dimensional (3D) in-vivo arterial morphology is
      therefore vital for endovascular device design, and preoperative planning of
      percutaneous interventions. The aim of this work was to establish geometric
      parameters describing arterial branch origin, trajectory, and vessel curvature in
      3D space that eliminate the errors implicit in planar measurements. 3D branching
      parameters at visceral and aortic bifurcation sites, as well as arterial
      tortuosity were determined from vessel centerlines derived from magnetic
      resonance angiography data for three subjects. Errors in coronal measurements of
      3D branching angles for the right and left renal arteries were 3.1 +/- 3.4
      degrees and 7.5 +/- 3.7 degrees , respectively. Distortion of the anterior
      visceral branching angles from sagittal measurements was less pronounced.
      Asymmetry in branching and planarity of the common iliac arteries was observed at
      aortic bifurcations. The renal arteries possessed considerably greater 3D
      curvature than the abdominal aorta and common iliac vessels with mean average
      values of 0.114 +/- 0.015 and 0.070 +/- 0.019 mm(-1) for the left and right,
      respectively. In conclusion, planar projections misrepresented branch trajectory,
      vessel length, and tortuosity proving the importance of 3D geometric
      characterization for possible applications in planning of endovascular
      interventional procedures and providing parameters for endovascular device
      design.

PMID- 17431788
TI  - Modeling of microbial population responses to time-periodic concentrations of
      antimicrobial agents.
AB  - We present the development and first experimental validation of a mathematical
      modeling framework for predicting the eventual response of heterogeneous
      (distributed-resistance) microbial populations to antimicrobial agents at time
      periodic (hence pharmacokinetically realistic) concentrations. Our mathematical
      model predictions are validated in a hollow-fiber in vitro experimental infection
      model. They are in agreement with the threshold levofloxacin exposure necessary
      to suppress resistance development of Pseudomonas aeruginosa in a murine thigh
      infection model. Predictions made by the proposed mathematical modeling framework
      can offer guidance for targeted testing of promising regimens. This can aid the
      development and clinical use of antimicrobial agents that combat microbial
      resistance.

PMID- 17431789
TI  - Spatio-temporal flow analysis in bileaflet heart valve hinge regions: potential
      analysis for blood element damage.
AB  - Point-wise velocity measurements have been traditionally acquired to estimate
      blood damage potential induced by prosthetic heart valves with emphasis on peak
      values of velocity magnitude and Reynolds stresses. However, the inherently
      Lagrangian nature of platelet activation and hemolysis makes such measurements of
      limited predictive value. This study provides a refined fluid mechanical
      analysis, including blood element paths and stress exposure times, of the hinge
      flows of a CarboMedics bileaflet mechanical heart valve placed under both mitral
      and aortic conditions and a St Jude Medical bileaflet valve placed under aortic
      conditions. The hinge area was partitioned into characteristic regions based on
      dominant flow structures and spatio-temporal averaging was performed on the
      measured velocities and Reynolds shear stresses to estimate the average bulk
      stresses acting on blood elements transiting through the hinge. A first-order
      estimate of viscous stress levels and exposure times were computed. Both forward
      and leakage flow phases were characterized in each partition by dynamic flows
      dependent on subtle leaflet movements and transvalvular pressure fluctuations.
      Blood elements trapped in recirculation regions may experience exposure times as
      long as the entire forward flow phase duration. Most calculated stresses were
      below the accepted blood damage threshold. Estimates of the stress levels
      indicate that the flow conditions within the boundary layers near the hinge and
      leaflet walls may be more detrimental to blood cells than bulk flow conditions,
      while recirculation regions may promote thrombus buildup.

PMID- 17431791
TI  - Regulation of cyclin-dependent kinase inhibitor p21WAF1/CIP1 by protein kinase
      Cdelta-mediated phosphorylation.
AB  - Cyclin-dependent kinase (CDK) inhibitor p21(WAF1/CIP1(-/-))-null mice have an
      increased incidence of tumor formation. Here, we demonstrate that p21(WAF1/CIP1)
      is unstable in HeLa cells treated with siRNA duplexes that target PKCdelta.
      PKCdelta phosphorylates p21(WAF1/CIP1 )at a serine residue ((146)Ser) located in
      its C-terminal domain. In cells treated with 12-O-tetradecanoylphorbol 13
      acetate, the levels of both p21(WAF1/CIP1) and its (146)Ser-phosphorylated form
      increased significantly. We also show that a substitution, resulting from a
      single nucleotide polymorphism (SNP) at (149)Asp found in certain cancer
      patients, strongly compromises PKCdelta-mediated phosphorylation at (146)Ser and
      results in cells that are relatively resistant to TNFalpha-induced apoptosis.
      Thus, post-translational phosphorylation of p21(WAF1/CIP1) is important from an
      apoptotic cell death, and may also have patho-physiological relevance for the
      development of human cancer.

PMID- 17431790
TI  - Acute acidification or amiloride treatment suppresses the ability of Hsp70 to
      inhibit heat-induced apoptosis.
AB  - Inhibition of stress-induced apoptosis by the molecular chaperone protein Hsp70
      is a contributing factor in tumorigenesis and suppression of this ability could
      increase the effectiveness of anti-tumor therapy. Tumor cells exist in an acidic
      environment and acute acidification can sensitize tumor cells to heat-induced
      cell death. However, the ability of Hsp70 to prevent apoptosis under these
      conditions has not been examined. The effect of acute acidification on heat
      induced apoptosis was examined in a human T-cell line with tetracycline-regulated
      Hsp70 expression. Apoptosis was inhibited in cells exposed to hyperthermia in
      acidic media when examined 6 h after the heat stress, but resumed if cells were
      returned to physiological pH during this recovery period. Long-term proliferation
      assays showed that acute acidification sensitized cells to heat-induced
      apoptosis. Hsp70 expressing cells were also sensitized and this was correlated
      with a reduced ability to suppress the activation of JNK (c-jun N-terminal
      kinase), Bax and caspase-3. Further sensitization could be achieved with the NHE1
      (Na(+)/H(+) exchanger) inhibitor HMA (5-(N, N-hexamethylene) amiloride), which
      potentiated JNK activation in heat-shocked cells. These results demonstrate that
      the ability of Hsp70 to suppress apoptosis is compromised when cells are exposed
      to hyperthermia in an acidic environment, which is correlated with an impaired
      ability to inhibit JNK activation.

PMID- 17431792
TI  - Bid is cleaved upstream of caspase-8 activation during TRAIL-mediated apoptosis
      in human osteosarcoma cells.
AB  - TRAIL induces apoptosis in many malignant cell types. In this study, we used the
      human papilloma virus (HPV) 16 E6 protein as a molecular tool to probe the TRAIL
      pathway in HCT116 colon carcinoma cells and U2OS osteosarcoma cells.
      Intriguingly, we found that while E6 protected HCT116 cells from TRAIL, U2OS
      cells expressing E6 remained sensitive to TRAIL. Furthermore, silencing FADD and
      procaspase-8 expression with siRNA did not prevent TRAIL-induced apoptosis in
      U2OS cells. However, siBid provided significant protection from TRAIL, and the
      cleavage kinetics of Bid and caspase-8 revealed that Bid was cleaved prior to the
      activation of caspase-8. Cathepsin B activity in U2OS cells was significantly
      activated shortly after exposure to TRAIL, and the cathepsin B inhibitor,
      CA074Me, inhibited both TRAIL- and anti-DR5-mediated apoptosis and delayed the
      cleavage of Bid. These findings suggest that TRAIL activates a pathway dependent
      on Bid, but largely independent of FADD and caspase-8, in U2OS cells.

PMID- 17431793
TI  - Conformational change in the active center region of GST P1-1, due to binding of
      a synthetic conjugate of DXR with GSH, enhanced JNK-mediated apoptosis.
AB  - Treatment of cells with a synthetic conjugate of DXR with GSH via glutaraldehyde
      (GSH-DXR) caused cytochrome c to be released from the mitochondria to the cytosol
      following potent activation of caspase-3 and -9 by typical DNA fragmentation.
      This apoptosis was regulated by the JNK-signaling pathway. In the present
      experiment, binding of GSH-DXR to GST P1-1 allosterically led to the
      disappearance of its enzyme activity and activated the kinase activity of JNK
      without dissociation of the JNK-GST P1-1 complex. The recombinant GST P1-1
      molecule with a mutation in the active center region (W38H and C47S) lost its GST
      activity when bound to JNK to the same degree as the wild-type, with the mutated
      GST P1-1 molecule failing to inhibit the activity of JNK. It has been reported
      that JNK-signaling is regulated by GST P1-1 via interaction with the C-terminus.
      We confirmed that GST P1-1 deletion mutant (Delta194-209) and a site-directed
      mutant (R201A) in the C-terminal region failed to bind and inhibit JNK. These
      results indicated that not only binding of the C-terminal region of GST P1-1 to
      the JNK molecule, but also the active center region of GST P1-1 play important
      roles in the regulation of JNK enzyme activity. The findings suggested that
      allosteric inhibition of GST P1-1 activity by the binding of GSH-DXR following
      conformational change may activate JNK and induce apoptosis via the mitochondrial
      pathway in the cells.

PMID- 17431794
TI  - Serum IGF-I levels in the diagnosis and monitoring of acromegaly.
AB  - Insulin-Like Growth Factor-I (IGF-I) is a reliable marker of disease activity and
      growth hormone (GH) status in acromegaly, but its clinical utility has been
      hampered over the years by various issues including a lack of robust reference
      range data and variability in assay sensitivity and specificity. In acromegaly
      IGF-I correlates well with GH activity and nadir GH on oral glucose tolerance
      test (OGTT) and is the most sensitive and specific test in diagnosis, where serum
      IGF-I is persistently seen to be elevated to a range that is distinct from that
      in healthy individuals. However it should not be relied on exclusively for
      diagnosis or used as the sole indication of disease severity and GH burden.
      Successful medical or surgical treatment of acromegaly is usually associated with
      normalisation of serum IGF-I but there is discordance between GH and IGF-I in
      some patients. Patients with a normal IGF-I but an abnormal GH suppression to
      OGTT are at risk of relapse and therefore it should not be used alone to
      establish disease remission. In contrast to the diagnosis of acromegaly, there is
      also considerable overlap in serum IGF-I with normality after primary treatment
      of disease, even in the presence of persisting GH excess. Gender, age and prior
      radiotherapy alters the relationship between GH and IGF-I and reliance on one
      marker of disease activity such as IGF-I is particularly precarious in certain
      disease states. However an elevated serum IGF-I has been shown to be associated
      with excess mortality and normalising IGF-I normalises mortality making it a
      useful marker. The tightening up of the assays means that establishing absolute
      concentrations as well as standard deviation scores are essential to allow cross
      study comparisons. This becomes especially important in the use of Pegvisomant,
      where IGF-I becomes the sole biochemical marker of disease activity.

PMID- 17431795
TI  - Buying and selling "loosies" in Baltimore: the informal exchange of cigarettes in
      the community context.
AB  - Since the release of the first Surgeon General's report, the proportion of adult
      smokers in the U.S. has been reduced by half (U.S. Department of Health and Human
      Services, 2004). This success has not, however, been equally felt across all
      social strata. Recent survey data from Baltimore show considerably elevated
      smoking rates within urban, African-American communities. Of particular concern
      was that in some communities, over half of the young adults (18-24 years old)
      smoke cigarettes. As yet, there has been little focus on understanding or
      preventing cigarette smoking among young adults, particularly for those seeking
      entry into the workforce rather than being engaged in higher education. In this
      paper, we explore community factors contributing to high young adult smoking
      prevalence. Our analysis is based on data from four focus groups conducted in
      2004 as part of a community-based participatory research project with two urban
      education and job training organizations. The focus group data reflect the
      experiences and opinions of 28 young adult program participants (23 smokers and 5
      nonsmokers). The data highlight a normalized practice of buying and selling
      single cigarettes ("loosies") within the community, with participants describing
      buying loose cigarettes as a preferred acquisition practice. We apply theories of
      informal economy and suggest that this alternative purchasing option may
      influence the smoking behavior of these young adults. We argue that public health
      efforts need to more closely consider the impact of community structures on
      program implementation. Overlooking key community characteristics such as the
      availability of single cigarettes may serve to intensify health disparities.

PMID- 17431796
TI  - The prevention and control of HIV/AIDS, TB and Vector-borne diseases in informal
      settlements: challenges, opportunities and insights.
AB  - Today's urban settings are redefining the field of public health. The complex
      dynamics of cities, with their concentration of the poorest and most vulnerable
      (even within the developed world) pose an urgent challenge to the health
      community. While retaining fidelity to the core principles of disease prevention
      and control, major adjustments are needed in the systems and approaches to
      effectively reach those with the greatest health risks (and the least resilience)
      within today's urban environment. This is particularly relevant to infectious
      disease prevention and control. Controlling and preventing HIV/AIDS, tuberculosis
      and vector-borne diseases like malaria are among the key global health
      priorities, particularly in poor urban settings. The challenge in slums and
      informal settlements is not in identifying which interventions work, but rather
      in ensuring that informal settlers: (1) are captured in health statistics that
      define disease epidemiology and (2) are provided opportunities equal to the rest
      of the population to access proven interventions. Growing international attention
      to the plight of slum dwellers and informal settlers, embodied by Goal 7 Target
      11 of the Millennium Development Goals, and the considerable resources being
      mobilized by the Global Fund to fight AIDS, TB and malaria, among others, provide
      an unprecedented potential opportunity for countries to seriously address the
      structural and intermediate determinants of poor health in these settings. Viewed
      within the framework of the "social determinants of disease" model, preventing
      and controlling HIV/AIDS, TB and vector-borne diseases requires broad and
      integrated interventions that address the underlying causes of inequity that
      result in poorer health and worse health outcomes for the urban poor. We examine
      insights into effective approaches to disease control and prevention within poor
      urban settings under a comprehensive social development agenda.

PMID- 17431797
TI  - Mammary gland involution as a multi-step process.
AB  - Mammary gland involution is a highly complex multi-step process in which the
      lactating gland returns to a morphologically near pre-pregnant state. This
      developmental stage is characterized by a high degree of epithelial cell death,
      redevelopment of the mammary adipose tissue and tissue remodelling. Many factors
      involved have been described and these have been reviewed intensively in this
      journal (Furth, P. A., J. Mammary Gland Biol. Neoplasia, 4:123-127, 1999) and
      elsewhere. Microarray analysis technology has now not only allowed us to identify
      genes not previously associated with involution (Stein, T., Morris, J.S., Davis,
      C.R.,Weber-Hall, S.J., Duffy, M.A., Heath, V.J., et al., Breast Cancer Res., 6:
      R75-R91, 2004; Clarkson, R.W., Wayland, M.T., Lee, J., Freeman, T., Watson, C.J.,
      Breast Cancer Res., 6: R92-R109, 2004; Clarkson, R.W., Watson, C.J., J. Mammary
      Gland Biol. Neoplasia, 8: 309-319, 2003), it has also enabled us to define
      multiple phases of the controlled regulatory response to forced weaning on the
      basis of their transcriptional profiles. This review provides a synthesis of
      published data, integrating the time course of transcriptional activity in the
      mouse mammary gland with a gene ontology approach to identify the pathways
      involved.

PMID- 17431798
TI  - The fur seal-a model lactation phenotype to explore molecular factors involved in
      the initiation of apoptosis at involution.
AB  - Mammary gland involution requires co-ordination of milk production, immune
      responses, apoptosis and remodeling. Initiation and progression of each of these
      components involves integral control by the mammary gland. Although cell-based
      culture models and genetically manipulated animals have shed light on these
      processes, the factors controlling each step in the involution cascade are still
      poorly understood. The fur seal displays a unique lactation phenotype. During the
      lactation cycle the mammary gland downregulates milk production and initiates an
      immune response but fails to initiate the apoptotic phase of involution, allowing
      the female fur seal to undertake long foraging trips of up to 28 days between
      suckling bouts. Upon return to shore the female continues feeding her pup
      following resumption of lactation and milk production. Expression profiling of
      genes involved in this lactation cycle provides valuable tools for investigation
      of the factors responsible for the initiation of apoptosis at involution.

PMID- 17431799
TI  - Three species of Skrjabinelazia Sypliaxov, 1930 (Nematoda: Seuratidae) parasitic
      in Gekkonidae and Lacertidae from South Africa, Europe and Australia.
AB  - Skrjabinelazia Sypliaxov, 1930 comprises 10 species distinguished by several
      characters typical of the genus including, among the most important, the
      presence/absence of spicules, cuticle ornamentation and vesicles, head-shape, the
      presence/absence of a leaflet crown in the buccal cavity, female tail-shape and
      male cone-shape. The three samples studied are new species: S. boomkeri n. sp., a
      parasite of Pachydactylus turneri, Gekkonidae, from South Africa (Klaserie
      Reserve); S. vozae n. sp., a parasite of Lacerta vivipara, Lacertidae, from
      France (Cevennes), which is close to two lacertid parasites, S. taurica
      Sypliaxov, 1930 and L. hoffmanni Li, 1934, respectively from the Crimea and North
      China (Peking); and S. mawsangelae n. sp. (male unknown), a parasite of
      Christinus marmoratus, Gekkonidae, from Australia (Pearson Island), which is,
      surprisingly, distinct from Skrjabinelazia sp. of Angel & Mawson (1968) from the
      same host in another region (North of Adelaide) of South Australia. Two main
      groups are distinguished in Skrjabinelazia: the species with spicules which are
      parasitic in the Lacertidae, and the species with a gubernaculum only which are
      parasitic in the Gekkonidae. The unique species described from the Iguanidae, S.
      intermedia (Freitas, 1940) from Brazil (Para), also without spicules, seems to be
      derived from gekkonid parasites, as it also has an evolved oesophagus with a
      glandular region, unlike the simple oesophagus seen in the larval stages of
      Skrjabinelazia.

PMID- 17431800
TI  - Mercury contamination and health risk to crops around the zinc smelting plant in
      Huludao City, northeastern China.
AB  - The Huludao zinc plant in Liaoning province, northeast China was the largest in
      Asia, and its smelting activities had seriously contaminated soil, water and
      atmosphere in the surrounding area. For the first time, we investigated the total
      mercury (THg) content in maize, soybean, broomcorn, 22 vegetables, and the soil
      around their roots from eight sampling plots near the Huludao zinc plant. THg
      contents of the seeds of maize, soybean, and broomcorn are 0.008, 0.006, and
      0.057 mg kg(-1), respectively, with the broomcorn being the highest, exceeding
      the maximum level of contaminant in food (GB2762-2005) by 4.7 times. The edible
      parts of vegetables are also contaminated with a range of mercury contents of
      0.001-0.147 mg kg(-1) (dry weight). THg contents in plant tissue decrease in the
      order of leaves > root > stalk > grain. Using correlation analysis, we show that
      mercury in the roots of these plants is mainly derived from soil, and the uptake
      of gaseous mercury is the predominant path by which the mercury accumulated in
      the foliage. The average and maximum mercury daily intake (DI) of adult around
      the Huludao zinc plant via consuming vegetables are 0.015 and 0.051 microg/kg/d,
      respectively, and those of children are 0.02 and 0.07 microg/kg/d, respectively.
      The average and maximum weekly intakes of total mercury for adult are 2.1 and
      7.1%, respectively, of the provisional tolerable weekly intake (PTWI), and 2.8
      and 9.7%, respectively, of the PTWI for children.

PMID- 17431802
TI  - Biodegradation of cypermethrin by Micrococcus sp. strain CPN 1.
AB  - A bacterium capable of utilizing pyrethroid pesticide cypermethrin as sole source
      of carbon was isolated from soil and identified as a Micrococcus sp. The organism
      also utilized fenvalerate, deltamethrin, perimethrin, 3-phenoxybenzoate, phenol,
      protocatechuate and catechol as growth substrates. The organism degraded
      cypermethrin by hydrolysis of ester linkage to yield 3-phenoxybenzoate, leading
      to loss of its insecticidal activity. 3-Phenoxybenzoate was further metabolized
      by diphenyl ether cleavage to yield protocatechuate and phenol as evidenced by
      isolation and identification of metabolites and enzyme activities in the cell
      free extracts. Protocatechuate and phenol were oxidized by ortho-cleavage
      pathway. Thus, the organism was versatile in detoxification and complete
      mineralization of pyrethroid cypermethrin.

PMID- 17431801
TI  - Mobilization of heavy metals from contaminated paddy soil by EDDS, EDTA, and
      elemental sulfur.
AB  - For enhanced phytoextraction, mobilization of heavy metals (HMs) from the soil
      solid phase to soil pore water is an important process. A pot incubation
      experiment mimicking field conditions was conducted to investigate the
      performance of three soil additives in mobilizing HMs from contaminated paddy
      soil (Gleyi-Stagnic Anthrosol): the [S, S]-isomer of ethylenediamine disuccinate
      (EDDS) with application rates of 2.3, 4.3, and 11.8 mmol kg(-1) of soil,
      ethylenediamine tetraacetate (EDTA; 1.4, 3.8, and 7.5 mmol kg(-1)), and elemental
      sulfur (100, 200, and 400 mmol kg(-1)). Temporal changes in soil pore water HM
      and dissolved organic carbon concentrations and pH were monitored for a period of
      119 days. EDDS was the most effective additive in mobilizing soil Cu. However,
      EDDS was only effective during the first 24 to 52 days, and was readily
      biodegraded with a half-life of 4.1 to 8.7 days. The effectiveness of EDDS
      decreased at the highest application rate, most probably as a result of depletion
      of the readily desorbable Cu pool in soil. EDTA increased the concentrations of
      Cu, Pb, Zn, and Cd in the soil pore water, and remained effective during the
      whole incubation period due to its persistence. The highest rate of sulfur
      application led to a decrease in pH to around 4. This increased the pore water HM
      concentrations, especially those of Zn and Cd. Concentrations of HMs in the soil
      pore water can be regulated to a large extent by choosing the proper application
      rate of EDDS, EDTA, or sulfur. Hence, a preliminary work such as our pot
      experiment in combination with further plant experiments (not included in this
      study) will provide a good tool to evaluate the applicability of different soil
      additives for enhanced phytoextraction of a specific soil.

PMID- 17431803
TI  - Structure and denaturation of 4-chlorobenzoyl coenzyme A dehalogenase from
      Arthrobacter sp. strain TM-1.
AB  - The secondary structure of the trimeric protein 4-chlorobenzoyl coenzyme A
      dehalogenase from Arthrobacter sp. strain TM-1, the second of three enzymes
      involved in the dechlorination of 4-chlorobenzoate to form 4-hydroxybenzoate, has
      been examined. E(mM) for the enzyme was 12.59. Analysis by circular dichroism
      spectrometry in the far uv indicated that 4-chlorobenzoyl coenzyme A dehalogenase
      was composed mostly of alpha-helix (56%) with lesser amounts of random coil
      (21%), beta-turn (13%) and beta-sheet (9%). These data are in close agreement
      with a computational prediction of secondary structure from the primary amino
      acid sequence, which indicated 55.8% alpha-helix, 33.7% random coil and 10.5%
      beta-sheet; the enzyme is, therefore, similar to the 4-chlorobenzoyl coenzyme A
      dehalogenase from Pseudomonas sp. CBS-3. The three-dimensional structure,
      including that of the presumed active site, predicted by computational analysis,
      is also closely similar to that of the Pseudomonas dehalogenase. Study of the
      stability and physicochemical properties revealed that at room temperature, the
      enzyme was stable for 24 h but was completely inactivated by heating to 60
      degrees C for 5 min; thereafter by cooling at 1 degrees C min(-1) to 45 degrees
      C, 20.6% of the activity could be recovered. Mildly acidic (pH 5.2) or alkaline
      (pH 10.1) conditions caused complete inactivation, but activity was fully
      recovered on returning the enzyme to pH 7.4. Circular dichroism studies also
      indicated that secondary structure was little altered by heating to 60 degrees C,
      or by changing the pH from 7.4 to 6.0 or 9.2. Complete, irreversible destruction
      of, and maximal decrease in the fluorescence yield of the protein at 330-350 nm
      were brought about by 4.5 M urea or 1.1 M guanidinium chloride. Evidence was
      obtained to support the hypothetical three-dimensional model, that residues W140
      and W167 are buried in a non-polar environment, whereas W182 appears at or close
      to the surface of the protein. At least one of the enzymes of the dehalogenase
      system (the combined 4-chlorobenzoate:CoA ligase, the dehalogenase and 4
      hydroxybenzoyl coenzyme A thioesterase) appears to be capable of association with
      the cell membrane.

PMID- 17431804
TI  - Ventilation during air breathing and in response to hypercapnia in 5 and 16 month
      old mdx and C57 mice.
AB  - Previous studies have shown a blunted ventilatory response to hypercapnia in mdx
      mice older than 7 months. We test the hypothesis that in the mdx mice ventilatory
      response changes with age, concomitantly with the increased functional impairment
      of the respiratory muscles. We thus studied the ventilatory response to CO(2) in
      5 and 16 month-old mdx and C57BL10 mice (n = 8 for each group). Respiratory rate
      (RR), tidal volume (VT), and minute ventilation (VE) were measured, using whole
      body plethysmography, during air breathing and in response to hypercapnia (3, 5
      and 8% CO(2)). The ventilatory protocol was completed by histological analysis of
      the diaphragm and intercostals muscles. During air breathing, the 16 month-old
      mdx mice showed higher RR and, during hypercapnia (at 8% CO(2) breathing),
      significantly lower RR (226 +/- 26 vs. 270 +/- 21 breaths/min) and VE (1.81 +/-
      0.35 vs. 3.96 +/- 0.59 ml min(-1) g(-1)) (P < 0.001) in comparison to C57BL10
      controls. On the other hand, 5 month-old C57BL10 and mdx mice did not present any
      difference in their ventilatory response to air breathing and to hypercapnia. In
      conclusion, this study shows similar ventilation during air breathing and in
      response to hypercapnia in the 5 month-old mdx and control mice, in spite of
      significant pathological structural changes in the respiratory muscles of the mdx
      mice. However in the 16 month-old mdx mice we observed altered ventilation under
      air and blunted ventilation response to hypercapnia compared to age-matched
      control mice. Ventilatory response to hypercapnia thus changes with age in mdx
      mice, in line with the increased histological damage of their respiratory
      muscles.

PMID- 17431805
TI  - Insulin-like growth factor I (IGF-I) in a growth-enhanced transgenic (GH
      overexpressing) bony fish, the tilapia (Oreochromis niloticus): indication for a
      higher impact of autocrine/paracrine than of endocrine IGF-I.
AB  - Several lines of growth hormone (GH)-overexpressing fish have been produced and
      analysed for growth and fertility parameters. However, only few data are
      available on the growth-promoting hormone insulin-like growth factor I (IGF-I)
      that mediates most effects of GH, and these are contradictory. Using quantitative
      real-time RT-PCR, radioimmunoassay, in situ hybridization, immunohistochemistry,
      and radiochromatography we investigated IGF-I and IGF binding proteins (IGFBPs)
      in an adult (17 months old) transgenic (GH-overexpressing) tilapia (Oreochromis
      niloticus). The transgenics showed an around 1.5-fold increase in length and an
      approximately 2.3-fold higher weight than the non-transgenics. Using
      radioimmunoassay, the serum IGF-I levels were lower (6.22 +/- 0.75 ng/ml) in
      transgenic than in wild-type (15.01 +/- 1.49 ng/ml) individuals (P = 0.0012).
      Radioimmunoassayable IGF-I in transgenic liver was 4.2-times higher than in wild
      type (16.0 +/- 2.21 vs. 3.83 +/- 0.71 ng/g, P = 0.0017). No hepatocytes in wild
      type but numerous hepatocytes in transgenic liver contained IGF-I
      immunoreactivity. RT-PCR revealed a 1.4-times higher IGF-I mRNA expression in the
      liver of the transgenics (10.51 +/- 0.82 vs. 7.3 +/- 0.49 pg/microg total RNA, P
      = 0.0032). In correspondence, in situ hybridization showed more IGF-I mRNA
      containing hepatocytes in the transgenics. A twofold elevated IGF-I mRNA
      expression was determined in the skeletal muscle of transgenics (0.33 +/- 0.02
      vs. 0.16 +/- 0.01 pg/microg total RNA, P < 0.0001). Both liver and serum of
      transgenics showed increased IGF-I binding. The increased IGFBP content in the
      liver may lead to retention of IGF-I, and/or the release of IGF-I into the
      circulation may be slower resulting in accumulation of IGF-I in the hepatocytes.
      Our results indicate that the enhanced growth of the transgenics likely is due to
      enhanced autocrine/paracrine action of IGF-I in extrahepatic sites, as shown here
      for skeletal muscle.

PMID- 17431806
TI  - Efficient dsRNA-mediated transgenic resistance to Beet necrotic yellow vein virus
      in sugar beets is not affected by other soilborne and aphid-transmitted viruses.
AB  - Rhizomania caused by Beet necrotic yellow vein virus (BNYVV) is one of the most
      devastating sugar beet diseases. Sugar beet plants engineered to express a 0.4 kb
      inverted repeat construct based on the BNYVV replicase gene accumulated the
      transgene mRNA to similar levels in leaves and roots, whereas accumulation of the
      transgene-homologous siRNA was more pronounced in roots. The roots expressed high
      levels of resistance to BNYVV transmitted by the vector, Polymyxa betae.
      Resistance to BNYVV was not decreased following co-infection of the plants with
      Beet soil borne virus and Beet virus Q that share the same vector with BNYVV.
      Similarly, co-infection with the aphid-transmitted Beet mild yellowing virus,
      Beet yellows virus (BYV), or with all of the aforementioned viruses did not
      affect the resistance to BNYVV, while they accumulated in roots. These viruses
      are common in most of the sugar beet growing areas in Europe and world wide.
      However, there was a competitive interaction between BYV and BMYV in sugar beet
      leaves, as infection with BYV decreased the titres of BMYV. Other interactions
      between the viruses studied were not observed. The results suggest that the
      engineered resistance to BNYVV expressed in the sugar beets of this study is
      efficient in roots and not readily compromised following infection of the plants
      with heterologous viruses.

PMID- 17431807
TI  - Down-regulation of pyrophosphate: fructose 6-phosphate 1-phosphotransferase (PFP)
      activity in sugarcane enhances sucrose accumulation in immature internodes.
AB  - Pyrophosphate: fructose 6-phosphate 1-phosphotransferase (PFP) activity was
      successfully down-regulated in sugarcane using constitutively expressed antisense
      and untranslatable forms of the sugarcane PFP-beta gene. In young internodal
      tissue activity was reduced by up to 70% while no residual activity could be
      detected in mature tissues. The transgenic plants showed no visible phenotype or
      significant differences in growth and development under greenhouse and field
      conditions. Sucrose concentrations were significantly increased in the immature
      internodes of the transgenic plants but not in the mature internodes. This
      contributed to an increase in the purity of the immature tissues, resembling an
      early ripening phenotype. Both the immature and mature internodes of the
      transgenic plants had significantly higher fibre contents. These findings suggest
      that PFP influences the ability of young, biosynthetically active sugarcane culm
      tissue to accumulate sucrose but that the equilibrium of the glycolytic
      intermediates, including the stored sucrose, is restored when ATP-dependent
      phosphofructokinase and the residual PFP activity is sufficient to sustain the
      required glycolytic flux as the tissue matures. Moreover, it suggests a role for
      PFP in glycolytic carbon flow, which could be rate limiting under conditions of
      high metabolic activity.

PMID- 17431808
TI  - Evaluation and reconstruction of an extremely rare genitourinary abnormality.

PMID- 17431809
TI  - Seminal vesicle invasion in radical prostatectomies: which is the most common
      route of invasion?
AB  - INTRODUCTION: Very few studies have been published on seminal vesicle invasion
      (SVI), and these have obtained conflicting results. The aim of the present
      investigation was to determine the most frequent of three possible routes of
      seminal vesicle invasion: (1) extraprostatic extension (EPE) into soft tissue
      adjacent to the seminal vesicle and then into the wall of the seminal vesicle,
      (2) invasion via the sheath of the ejaculatory duct, penetrating the muscular
      wall of the ejaculatory duct or extending up the ejaculatory duct into the
      seminal vesicle muscle wall, or (3) discontinuous metastases. MATERIALS AND
      METHODS: The surgical specimens of 230 consecutive patients submitted to radical
      prostatectomy were histologically evaluated by complete embedding and whole-mount
      processing. RESULTS: Of the surgical specimens obtained from 230 patients, 28
      (12.17%) showed the presence of either unilateral or bilateral SVI. The routes of
      SVI in these 28 specimens were: (1) only via the sheath of the ejaculatory duct
      (0/28; 0%); (2) discontinuous metastases (3/28; 11%), (3) both EPE and via the
      sheath of the ejaculatory duct (6/28; 21%), and (4) only EPE (19/28; 68%). One
      half (14/28; 50%) of the 28 seminal vesicles involved had unilateral invasion
      and, in most of these cases (42.85%), EPE was unilateral and ipsilateral.
      CONCLUSION: Our results suggest that the most important and most frequent route
      of SVI is extraprostatic extension of prostate carcinoma into the soft tissue
      adjacent to the ipsilateral seminal vesicle and then into the wall of the seminal
      vesicle.

PMID- 17431810
TI  - Case report: differential diagnosis of isolated iliac lymphadenopathy following
      Bacillus Calmette-Guerin treatment for high-risk superficial bladder cancer.
AB  - We report the unusual case of a patient with G3 pT1 transitional cell carcinoma
      (TCC) of the bladder, which was treated with repeated transurethral resection and
      maintenance intravesical Bacillus Calmette-Guerin (BCG) therapy. At 30 months
      follow-up, a symptomatic, solitary iliac lymph node mass was identified and
      biopsied. Histology demonstrated granulomatous tissue only, in the absence of any
      intravesical bladder tumour recurrence. Following 6 months of anti-tuberculous
      medication, the mass had progressed, and repeat biopsy revealed undifferentiated
      carcinoma (of a bladder primary). This is a rare case of metastatic superficial
      bladder cancer progression without local recurrence after BCG therapy. As such,
      it can be viewed as a diagnostic challenge.

PMID- 17431811
TI  - Prevalence of self-reported interstitial cystitis (IC) and interstitial-cystitis
      like symptoms among adult women in the community.
AB  - PURPOSE: Reported estimates of IC prevalence vary widely. The objective of this
      study is to determine the prevalence of IC among community-dwelling adult women.
      METHODS: We analyzed survey responses from 215 established IC cases and 823 age
      matched community-dwelling controls. Using a history of diagnosis of urinary
      conditions and presence of pelvic pain within the last six months, we identified
      those with possible IC among the controls using various operative definitions.
      RESULTS: The prevalence rates of self-reported IC (SRIC) and IC-like symptoms
      (ICLS) among controls in the community were 3.7% and 4.4%, respectively.
      Expanding ICLS by including women who reported pelvic pain only raised the
      prevalence to 17.3%. CONCLUSIONS: According to our prevalence rates and
      population estimates in the United States census 2000, the number of adult women
      who possibly have interstitial cystitis is estimated to be between 422,803 and
      21,454,813. Although estimates based on the question of having ever been
      diagnosed with IC lead to an estimate close to that derived from symptoms,
      underestimation of IC prevalence might occur in the absence of additional
      questions and testing to validate and qualify the responses further. There is
      also a need for clinical studies to verify and validate the diagnoses to enable
      accurate assessment of the sensitivity and specificity of such history survey
      questions.

PMID- 17431812
TI  - Comparison of transurethral prostate resection and plasmakinetic prostate
      resection according to cautery artefacts in tissue specimens.
AB  - OBJECTIVES: The objectives were to evaluate cautery artifacts histopathologically
      in tissue specimens after plasmakinetic prostate resection (PKRP) and
      transurethral prostatectomy (TURP), and compare the results of the two
      procedures. MATERIALS AND METHODS: The histopathological specimens of 65 patients
      who underwent PKRP and TURP were examined retrospectively. Tissue chips for
      examination were selected randomly. Artifactual pathological patterns that were
      identified in the specimens included: abnormal cellular orientation and
      spindling, artifactual cellular detachment from the underlying basement membrane,
      atypical cytological changes and stromal coagulative necrosis. Each pattern
      identified was awarded 1 point. The severity of the cautery artefact was graded
      as absent, mild, moderate or severe according to the sum of points in each
      specimen. RESULTS: In TURP, the artefacts were graded absent (9%), mild (6%),
      moderate (18.7%), and severe (65.6%) changes. In PKRP, the artefacts were graded
      absent (6%), mild (18.1%), moderate (36.3%), and severe (39.4%) changes. While
      the number of mild and moderate artefacts observed was higher in PKRP (P =
      0.023), severe artefacts were observed in higher numbers with TURP (P = 0.034).
      No prostate cancer was detected during the follow-up period. CONCLUSIONS: It has
      been observed that the application of TURP causes fewer mild to moderate
      artefacts and PKRP causes fewer severe artefacts in the histopathological
      evaluation of specimens in comparison to each other.

PMID- 17431813
TI  - Primary melanoma of the urethra: a rare neoplasm of the urinary tract.
AB  - Primary melanomas of the genitourinary tract are rare and constitute less than 1%
      of all melanomas. Since the clinical presentation of urethral melanoma is similar
      to commoner urothelial carcinomas, there is frequent delay in diagnosis. A 65
      year-old female presented with bleeding per urethra for 1 month. Cysto
      urethroscopy showed a gray-white polypoidal tumor in the distal urethra. A biopsy
      from the tumor showed sheets of cells with moderate cytoplasm, and central
      vesicular nucleus with prominent nucleolus. Immunohistochemistry for HMB-45 and S
      100 protein was positive in the tumor cells. A diagnosis of urethral melanoma was
      made and radical cysto-urethrectomy with total hysterectomy was done. There was
      no residual tumor in the urethra; however, sections from bladder neck showed
      pagetoid spread of melanoma cells in urothelium. No melanocytic lesion was found
      elsewhere, and a diagnosis of primary melanoma of urethra was rendered. Urethral
      melanomas are rare tumors, having clinical presentation similar to much commoner
      urothelial neoplasms. Due to the poor prognosis, the clinician and the
      pathologists should keep this diagnosis in mind when dealing with urethral tumors
      with unusual morphology.

PMID- 17431814
TI  - Do Finnish women using hormone replacement therapy need more information about
      risks.
AB  - OBJECTIVE: In 1998, the Women's Health Initiative (WHI) in 2002 and the Million
      Women Study (MWS) in 2003 have shown a need for re-evaluation of the benefits and
      adverse reactions of hormone replacement therapy (HRT). Consequently the
      authorities in Europe and USA have issued new recommendations against the use of
      HRT. The aim of this study was to examine women's perceptions of HRT since the
      publication of the Women's Health Initiative study and the Million Women Study,
      and the kind of sources women use to obtain information about HRT. METHOD: The
      data was collected with questionnaire survey in the autumn 2003 among 315 women
      using HRT. RESULTS: One third of the respondents (35%) had experienced fears
      concerning HRT use, and more than half (52%) reported that the debate in the
      media had markedly influenced them; they have experienced fears or worries,
      considered discontinuation or discussed with the physician. Whereas the most
      common source of information concerning the benefits of HRT was the physician
      (74%), the most common source of information concerning the risks of HRT was the
      media (78%). CONCLUSION: This study shows that women using HRT should get more
      information about the risks from health care professionals. Physicians and
      pharmacists have an opportunity to alleviate fears and to help women to
      critically evaluate the information they get from the media. Such discussions are
      also important to women who have been using HRT for years.

PMID- 17431817
TI  - Dietary long-chain polyunsaturated fatty acid supplementation in infants with
      phenylketonuria: a randomized controlled trial.
AB  - BACKGROUND: Pre- and postnatal tissue accretion of long-chain polyunsaturated
      fatty acids (LCPUFA) has been related to visual and cognitive development in
      healthy children in several studies. Children with phenylketonuria (PKU) consume
      diets with very low contents of preformed LCPUFA. We studied prospectively the
      LCPUFA status in infants with PKU without or with LCPUFA supplementation during
      the first year of life. SUBJECTS AND METHODS: Infants with PKU were enrolled at
      diagnosis (<4 weeks of age) and randomized double blind to phenylalanine-free
      amino acid supplements without LCPUFA (n = 11) or with both arachidonic (AA, 0.46
      wt%) and docosahexaenoic acids (DHA, 0.27 wt%) (n = 10). At enrolment and again
      at 1, 2, 3, 4, 6, 9 and 12 months, plasma phospholipid fatty acids were measured
      and dietary intakes were calculated from dietary protocols. RESULTS:
      Unsupplemented patients showed a marked LCPUFA depletion to levels clearly below
      those observed in healthy breast-fed infants. In contrast, supplemented infants
      had stable and higher LCPUFA levels than unsupplemented infants, reaching
      significant differences for AA values at 3, 4 and 6 months, and for DHA values at
      1, 3, 4, 6, 9 and 12 months. Plasma phospholipid levels correlated closely with
      estimated dietary intakes of preformed LCPUFA. CONCLUSION: Low LCPUFA intakes
      with PKU diets induce marked depletion of AA and particularly of DHA in the first
      year of life. Thus endogenous synthesis of LCPUFA from precursors supplied by
      diet seems unable to compensate for low LCPUFA intakes. LCPUFA supplementation of
      PKU diets during the first year of life effectively enhances LCPUFA status to
      levels comparable to those of healthy breast-fed infants.

PMID- 17431819
TI  - Detection of moderate regional ischemia in pig hearts in vivo by near-infrared
      and thermal imaging: effects of dipyridamole.
AB  - Effects of coronary vasodilator, dipyridamole, on epicardial oxygenation and flow
      were investigated under conditions of moderate coronary occlusion using near
      infrared spectroscopic (NIRS) and thermal imaging. In anesthetized open chest
      pigs an inflatable occluder and flow probe were placed around the left anterior
      descending artery (LAD). In the ischemic group (n = 11) LAD occlusion (50% flow,
      80 min) was followed by complete occlusion (10 min, n = 4), and reflow.
      Dipyridamole was infused (0.14 mg/min/kg/4 min) intravenously during 50%
      occlusion. In the control group (n = 6) LAD flow was temporarily increased
      (hyperemic response) by two 2-min periods of complete LAD occlusion applied 120
      min apart, with a 4-min period of dipyridamole infusion between the two
      occlusions. NIRS and thermal images were acquired throughout the protocol. Maps
      of subepicardial oxygen saturation parameter (OSP), and epicardial temperature
      (T) were obtained. Partial occlusion reduced OSP and the temperature by 0.23 +/-
      0.08 and 0.88 +/- 0.39 degrees C versus remote region, respectively. Dipyridamole
      decreased systolic blood pressure by 36%, which caused further decline in the LAD
      flow to 18% and OSP and T by 0.37 +/- 0.01 and 2.46 +/- 0.32 degrees C,
      respectively. Reflow restored OSP and T to their baseline levels. In control
      group dipyridamole and hyperemia increased LAD flow 2-4-fold associated with
      moderate increase in OSP and T. OSP and T showed linear dependence on the flow
      below 100%, which is leveled-off at flows above normal. Dipyridamole increases
      differences in the epicardial oxygenation and T between normal and moderately
      ischemic areas due to enhancement of disparity in perfusion of these areas.

PMID- 17431820
TI  - Study of Kir6.2/KCNJ11 gene in a sudden cardiac death pedigree.
AB  - In clinic, the patients with acute myocardial infarction (AMI) are at high risk
      to develop ischemia-induced ventricular arrhythmias leading to sudden cardiac
      death (SCD). Some studies suggest that individual susceptibility to ischemia
      induced arrhythmia may be related to the genes encoding ion channels. One of them
      is the cardiac ATP-sensitive potassium channel (K(ATP)), which is an octamer
      composed of four pore-forming inwardly rectifying potassium-channel subunits
      (Kir6.2) and four regulatory sulfonylurea-receptor subunits (SUR2A). They play
      important roles in the physiology and pathophysiology of cardiovascular system by
      coupling the metabolic state of the cells to cellular electrical activity. So
      far, some mutations and polymorphisms of Kir6.2/KCNJ11 gene showed significant
      correlation with type 2 diabetes. But it was not sure whether it was associated
      with acute myocardial diseases. Hence a complete mutational analysis of
      Kir6.2/KCNJ11 gene was performed in a pedigree of sudden cardiac death. The
      complete coding region and the intron-exon boundaries of KCNJ11 were amplified
      from genomic DNA using polymerase chain reaction (PCR). Direct sequencing was
      done to identify any mutations and then further confirmed by restriction site
      polymorphism (RSP) approach. No mutation was detected in the samples analyzed, a
      common polymorphism K23E (A>G) was noticed in this pedigree and the proband
      showed a homozygote genotype (G/G). The result suggests that the Kir6.2/KCNJ11
      gene is not related to sudden cardiac death in this family.

PMID- 17431818
TI  - A primer on motion visual evoked potentials.
AB  - Motion visual evoked potentials (motion VEPs) have been used since the late 1960s
      to investigate the properties of human visual motion processing, and continue to
      be a popular tool with a possible future in clinical diagnosis. This review first
      provides a synopsis of the characteristics of motion VEPs and then summarizes
      important methodological aspects. A subsequent overview illustrates how motion
      VEPs have been applied to study basic functions of human motion processing and
      shows perspectives for their use as a diagnostic tool.

PMID- 17431821
TI  - Coprinus comatus and Ganoderma lucidum interfere with androgen receptor function
      in LNCaP prostate cancer cells.
AB  - In this study, we screened a total of 201 diethyl ether, ethanol, and ethyl
      acetate fungal Basidiomycetes extracts for anti-androgenic activity. Based on our
      screened results in combination with the selective inhibition of prostate cancer
      LNCaP cells, we selected Coprinus comatus and Ganoderma lucidum for further
      evaluation. We demonstrated that ethanol and ethyl acetate extracts from C.
      comatus and G. lucidum, respectively, selectively inhibit dihydrotestosterone
      induced LNCaP cell viability, suppress levels of secreted prostate-specific
      antigen in a dose-dependent manner, and cause a G1 phase arrest in LNCaP, but not
      in DU 145 and PC-3 cells. For the first time, to the best of our knowledge, we
      demonstrated that C. comatus and G. lucidum decreased androgen and
      glucocorticoide receptors transcriptional activity in breast cancer MDA-kb2 cells
      in a dose-dependent manner, and suppressed androgen receptor (AR) protein level
      in LNCaP and MDA-kb2 cells. Our findings suggest that AR and non-AR mediated
      mechanisms underlie the effects of C. comatus and G. lucidum.

PMID- 17431822
TI  - Organ transplantation in Bulgaria.
AB  - The transplantation program in Bulgaria started in 1968 with renal
      transplantations to a child and adult woman. In 1986 the first heart
      transplantation was performed. To date a total of 10 heart transplants have been
      performed, including one combined heart/lung. A liver transplantation program was
      launched in 2005 with a total number of 16 transplantations-7 from living donors
      and 9 from deceased donors. The highest transplantation activity is registered in
      the field of renal transplantation. During the period 1980-2006, 462 Bulgarian
      recipients of kidney were transplanted in Bulgaria. The ratio between
      transplantations from deceased and living related donors is approximately 1:0.9.
      Annual transplantation activity varies among the years from 1 to 12 renal
      transplantations p.m.p./per year. The 1- (80.7% vs. 63.1%), 5- (57.86% vs. 39.0%)
      and 10-year (42.65% vs. 23.62%) graft survival rates are higher for recipients of
      living donor kidneys compared to those of deceased donor. In 1983 a National
      kidney waiting list was established. Currently the number of the registered
      patients eligible for renal transplantation is 885. The proportion of sensitized
      patients in the waiting list is 20.45% and 4.34% of them are hyperimmunized.
      Recently HLAMatchmaker program has been implemented not only for sensitized
      patients but also for those with rare alleles and haplotypes. Post-transplant
      immunological monitoring showed a strong association between alloantibody
      presence and delayed graft function (Chi-square=10.73, P<0.001), acute rejection
      (Chi-square=14.504, P<0.001), chronic rejection (Chi-square=12.84, P<0.001) and
      graft loss (Chi-square=20.283, P<0.001). Based on the experience in our
      transplant center a strategy for improvement of long-term renal graft survival
      was developed and implemented.

PMID- 17431823
TI  - Changes in arterial oxygen tension correlate with changes in end-expiratory
      carbon monoxide level.
AB  - OBJECTIVE: Carbon monoxide (CO) and oxygen compete for haemoglobin binding sites.
      While the effects of increased inspiratory oxygen fractions on exhaled carbon
      monoxide concentrations have been studied previously, the relationships between
      intravascular oxygen tension, blood carboxyhaemoglobin levels and expiratory CO
      concentrations remain unclear. We therefore studied the effects of increases in
      arterial oxygen tension as crucial determinant for the displacement of carbon
      monoxide from its haemoglobin bond during lung passage. METHODS: Measurements of
      end-expiratory CO concentrations (eCO), arterial oxygen tensions and
      carboxyhaemoglobin concentrations were performed in 19 patients while breathing
      air and oxygen. RESULTS: With increasing PaO(2) (from 11.5 +/- 1.9 to 35.2 +/-
      10.3 kPa) end-expiratory CO concentrations increased from 8.6 +/- 4.9 to 16.7 +/-
      9.4 ppm, p < 0.001, with a mean increase of 0.36 ppm CO per kPa increase in
      PaO(2) (DeltaeCO [ppm] = 0.36 * DeltaPaO(2 )[kPa]). Increases of arterial oxygen
      tension correlated with increases of end-expiratory CO concentration (r(2) =
      0.33). Arterial carboxyhaemoglobin concentrations decreased from 1.06 +/- 0.37
      during air breathing to 0.92 +/- 0.35 % after 5 minutes of oxygen inhalation (p <
      0.001). CONCLUSIONS: Oxygen-induced increases in exhaled CO correlate with
      increases in arterial oxygen tensions. Furthermore, oxygen inhalation reduces
      carboxyhaemoglobin levels, supporting the concept of accelerated CO elimination
      by oxygen via the lungs.

PMID- 17431824
TI  - Effect of Desmodium gangeticum extract on blood glucose in rats and on insulin
      secretion in vitro.
AB  - Desmodium gangeticum is widely used in the indigenous system of medicine in India
      and is reported to contain flavone and isoflavonoid glycosides. It forms the
      ingredient of many Ayurvedic formulations used for diabetes. The present study
      was thus aimed at evaluating the insulin secretion and antidiabetic activity of
      Desmodium gangeticum. Treatment of diabetic rats with aerial parts of D.
      gangeticum extract (DG, 100 and 250 mg/kg body weight) for 3 weeks showed a
      significant reduction in blood glucose. D. gangeticum extract caused a
      significant increase in insulin secretion from MIN6 cells grown as monolayers and
      as pseudoislets, indicating that the antidiabetic activity may be as a result of
      increased insulin secretion. It also had a role on the lipid profile of the rats
      by causing reductions in cholesterol and triglycerides and increasing the HDL
      significantly (p < 0.05). This works supports the traditional use of D.
      gangeticum in the treatment of diabetes and this is likely to be due, at least in
      part, to its stimulation of insulin secretion by pancreatic islet cells.

PMID- 17431825
TI  - In vivo antimalarial activity of isosungucine, an indolomonoterpenic alkaloid
      from Strychnos icaja.
AB  - Isosungucine (1) is a quasi-symmetric bisindolomonoterpenoid alkaloid isolated
      from the roots of Strychnos icaja. The in vivo antimalarial activity against the
      P. vinckei petteri murine strain was determined. In the Peters 4-day suppressive
      test, 1 suppressed the parasitemia by almost 50 percent on day 4 at the dose of
      30 mg/kg by intraperitoneal route.

PMID- 17431826
TI  - [Surgery of the nasal septum and turbinates].

PMID- 17431827
TI  - [Indications for and techniques of rhinoplasty].

PMID- 17431828
TI  - [Risks and complications of rhinoplasty].

PMID- 17431829
TI  - [Disorders of the nasa ali].

PMID- 17431830
TI  - [Implants for reconstructive surgery of the nose and ear].

PMID- 17431831
TI  - [Classification and diagnosis of ear abnormalities].

PMID- 17431832
TI  - [Techniques for antihelix plasty ].

PMID- 17431833
TI  - [Complications of antihelix plasty].

PMID- 17431834
TI  - [Reconstruction of the external ear].

PMID- 17431835
TI  - [Reconstruction of the middle ear in abnormalities].

PMID- 17431836
TI  - [Abortion counseling: strategies for interdisciplinary service].
AB  - Abortion has long been an issue of concern for professional groups in many
      fields, such as medicine, nursing, religion, feminist rights, psychology, and
      social work. Although these groups hold differing views on abortion as well as
      eugenics health care law revision, they share a consensus that counseling
      services should be provided for abortion in order that women are sufficiently
      informed to make a sound decision on whether or not to have an abortion. Thus,
      this paper discusses in detail counseling service in terms of background,
      workflow and approaches, and interdisciplinary integration, as well as offers
      suggestions for future development. Hopefully, this can serve as a reference for
      concerned about women's reproductive health and obstetrics service quality.

PMID- 17431837
TI  - [The dispute over Taiwan's genetic health law].
AB  - Population growth in Taiwan reached four hundred thousand births per year in the
      1980s. Responding to the challenges presented by this significant increase in the
      population, the government implemented the Genetic Health Law in 1985 to improve
      quality of life and provide relief to those with large families. The Law promoted
      health awareness, birth control and the legalization of abortion. Although this
      policy has significantly and successfully lowered the birthrate over the past 20
      years, abortion-related disputes have been on the rise in recent years. On side,
      womanfs rights activists argue that current Department of Health regulations that
      require the consent of a spouse or of parents, mandatory counseling and a
      deliberation period prior to obtaining an abortion violates a woman's autonomy.
      On the other side, religious groups appeal for a tightening of legal strictures
      in order to reduce the number of abortions as well as enforced counseling and a
      six-day deliberation period before an abortion could be permitted. As the
      Executive Yuan's deliberated over a proposed amendment to relevant laws,
      legislators were aggressively lobbied by both sides to support their respective
      positions. The polar positions stalemated a decision on the amendment by one vote
      during a Legislative Yuan vote on a draft amendment in January 2007. The author
      urges all parties to reconsider the proposed amendment rationally and hopes that
      the amendment can be passed in the near future.

PMID- 17431838
TI  - [The role, power and health of women].
AB  - Women's health issues, often addressed together with reproduction and children's
      health under the broad based "women and children's health" category, receive
      inadequate attention from the medical system. In retrospect, the social construct
      of the female role has been grounded in the physiological nature of sex. Thus,
      women are often treated based on their stereotypical roles (e.g., mother,
      daughter-in-law, wife, daughter) rather than on their needs as distinct
      individuals. Although modern society was built by women and men together,
      patriarchal values continue to relegate the social status and value of women to
      that of assistant. Social opportunity remains significantly different for men and
      women, with discrimination persisting. The status and value of women are often
      ignored in both the public and private sectors. While status and power influences
      the health of women, such mechanisms are rarely discussed in the medical field.
      This paper discusses how women's social status has been formed by social and
      economic development, how it has been ignored, and the influence of such
      developments on women's health.

PMID- 17431839
TI  - [Osteoporosis screening policy for menopausal women: risk and discipline].
AB  - The community-based osteoporosis screening program for menopausal women is an
      important service provided by community health nurses. This paper discusses how
      normalization technologies such as bone density screening help to discipline
      menopausal women conformed to normative behavior as to reduce bone loss risk. An
      analysis of osteoporosis screening policies found that mass surveillance
      technology perpetuates the knowledge of diseased menopausal body with
      osteoporosis. In addition, voluntary practices of self-surveillance represent the
      governmental strategy of disciplinary power by which menopausal women are
      monitored in the framework of neoliberalism emphasizing individual choice and
      freedom. Although unreliable, the Quantitative Ultrasound promoted by
      pharmaceutical companies has been participated eagerly by women in community
      osteoporosis screening activities. Self-surveillance measures further involve
      modifications in lifestyle (e.g., diet, exercise, daily activity, garments) to
      prevent bone loss and to lessen the risks of facing costly medical care bills.
      This paper suggests that health care professionals pay greater attention to
      menopausal women's opinions about their screening experiences and to the results
      of discussions on screening results. Better assessing screening policies should
      help facilitate a transformation in policy focus from self regulation to
      environmental modification.

PMID- 17431840
TI  - [Retrospective review and analysis of the results of taiwan nurses association
      nursing projects from 2004 to 2005].
AB  - Although a nursing project is one of the important N4 professional competence
      training courses in the clinical ladder system, little research on its
      effectiveness can be found. This study therefore aimed to analyze the
      demographics, hospital characteristics, scores, and pass rates for the Taiwan
      Nurses Association's 2004 to 2005 nursing projects and to compare the differences
      between them. The design was retrospective content analysis and the data sources
      were nursing project reviewer sheets from the years 2004 and 2005. Data were
      analyzed using descriptive statistics, such as number, percentage, mean, standard
      deviation, and Chi-square test, or Fisher exact test. We analyzed 1,062 nursing
      projects. Of these, 423 projects had third reviewers. After that, 2,547 reviewer
      sheets were used as final samples. The average project score was 59.7 points (SD
      = 9.3 points) and the majority of the projects were categorized as administrative
      and from medical centers, or private hospitals in northern areas of Taiwan. The
      pass rate was found to be higher in public hospitals, however, than in private
      hospitals. Almost all the projects (n = 2,515; 98.7%) included
      reviewers'comments. There was no significant difference between project pass rate
      and clinical specialty, scope, hospital location, and level of hospital
      accreditation (p > .05). A significant difference was found, however, between
      project scores and hospital characteristics (p = .01). These findings may serve
      as references in the development of future requirements for nursing projects in
      the clinical ladder system, to improve the quality and quantity of such projects.

PMID- 17431841
TI  - [Using focus groups to explore the group music therapy experience of long term
      care elderly].
AB  - The purpose of this study was to explore the elderly's experience and perceptions
      of group music therapy. The residents of a long term care institution received
      group music therapy for one year. Afterwards, three interviews were conducted in
      focus groups of between six and eight of the elderly. Their ages ranged from 64
      to 90. Ninety-five percent of these elderly subjects participated in the therapy
      for over ten months. The tape-recorded interviews were transcribed and analyzed
      using content analysis. Six themes emerged regarding the elderly subjects'
      experiences and perceptions of group music therapy, as follows: (1) becoming more
      willing to participate; (2) feeling pain relief and more controlled moods; (3)
      getting physically better; (4) being more motivated to live; (5) learning
      positive personal interaction and obedience to the rules of the group; and (6)
      learning skills to improve personal health. This information might be used as a
      helpful and valuable reference in nursing education and by administrative
      organizations involved in the planning of therapeutic programs for the elderly.

PMID- 17431842
TI  - ["Doing the month" experiences of Vietnamese primipara in Taiwan].
AB  - The number of transnational marriage families in Taiwan has been increasing in
      recent years, with Vietnam the country of origin for the largest number of women
      married to Taiwanese men. The typical Vietnamese wife married her Taiwanese
      husband at a very young age and had little prior familiarity with the Taiwan
      custom of "doing the month"--the period of enforced rest and recovery for
      postpartum mothers during the month after childbirth. The purpose of this
      qualitative study was to explore the experiences and feelings of Vietnamese
      primipara on "doing the month". Participants, recruited from two teaching
      hospitals in Kaohsiung City, were interviewed about their experiences and
      feelings about "doing the month" during home visits. Participant descriptions
      were then sorted and analyzed. Three key aspects related to "doing the month"
      identified by the research include (1) dieting, (2) bathing, and (3) homebound
      rest. By helping healthcare professionals better understand the "doing the month"
      experiences of Vietnamese primipara, study results can help facilitate the design
      and implementation of healthcare for this group to ensure access to comprehensive
      healthcare that considers their physical, psychological, and social-cultural
      needs.

PMID- 17431843
TI  - [A project to revise the patient needs rank assessment scale for discharge
      planning].
AB  - A comprehensive discharge planning assessment tool facilitates the provision of
      services that meet individual needs thus also facilitating the implementation of
      high-quality discharge planning. This project used a medical center in northern
      Taiwan as an example, applied interviews and the questionnaire method, and found
      that the sensitivity and specificity of existing rank assessment scales were all
      lower than the standard of 70%, too low to provide accurate screening for
      classification of needs. In revising the assessment items of, "The Patient Needs
      Rank Assessment Scale for Discharge Planning, a quantified score was set for the
      degree of need for each rank, to compute the cut point of each rank with the
      appropriate sensitivity and specificity. The results show that sensitivity and
      specificity after revision of the assessment scale all exceeded 70%. As far as
      satisfaction in clinical usage was concerned, personnel sought to match
      assessment standards with clinical patients'needs and accurately screened three
      grades of patient need. Initially, the increase in satisfaction was of clear
      statistical significance (p < .05). This showed that revision of, "The Patient
      Needs Rank Assessment Scale for Discharge Planning" can be applied to achieve
      accurate screening of patient need grades.

PMID- 17431844
TI  - [The principles of chronic wound assessment and measurement].
AB  - The management of chronic diseases in the elderly population is a major challenge
      for professional nurses. Chronic wounds, such as pressure ulcers, diabetic foot
      ulcers, venous ulcers, and arterial ulcers are common problems among patients
      with chronic diseases. This article aims to improve the knowledge base of nurses
      who assess and identify the etiology of chronic wounds, in the hope that an
      improved pool of knowledge can be drawn upon and applied in clinical practice.
      The article discusses patient assessment, chronic wound assessment, assessment of
      healing, and wound classification systems that can provide a structured approach
      to the management of chronic wounds. It provides a rational and systematic
      approach to both assessment and management that is particularly useful in the
      management of non-healing wounds. It can be used as a source of reference for
      nurses in the organization of wound management plans and the provision of better
      care for patients.

PMID- 17431845
TI  - [Appraisal: a concept analysis].
AB  - Appraisal is a cognitive response by an individual facing an event within a given
      environment. When the individual has passed through a thought process that gives
      the event meaning, the coping process is finally completed. Coping heightens an
      individual's well-being. Negative appraisal will induce an emotional coping
      response and affect one's quality of life, mental state and health. Several
      researchers applied the concept of appraisal to their disciplines. The concept of
      appraisal, however, is poorly defined. This article applies the methodology
      outlined by Walker and Avant (1995) to analyze the concept of appraisal. The
      definition of appraisal, examples, and empirical references provided in this
      paper will be useful in nursing practice in relation to the role of appraisal in
      coping.

PMID- 17431846
TI  - [Self-care for patients with frozen shoulder].
AB  - "Frozen shoulder" syndrome (adhesive capsulitis or pericapsulitis) refers to any
      kind of shoulder pain or to limited active or passive glenohumeral joint motions.
      Treatment options include both Chinese and western medical therapies. However,
      the key to recovery lies in self-care. This article addresses both Chinese and
      western treatments for frozen shoulder and suggests optimal treatments and self
      care approaches for this debilitating condition. Health professionals can help
      patients ease their pain and increase joint activity in order to prevent frozen
      shoulder from turning into chronic adhesive capsulitis.

PMID- 17431847
TI  - [Strategies for discussing death with child cancer sufferers].
AB  - Since a curriculum concerning life and death was established and palliative care
      began to be promoted, people have gradually awakened to the needs of dying
      patients. Because of the nature of oriental culture, however, ultimate decisions
      concerning someone with a terminal disease have traditionally been made by
      family, so dying patients, especially children with cancer, have usually not been
      told of their true condition. The purpose of this article was to gain an
      understanding of the necessity of talking about death with child cancer patients
      and how to communicate with these children. The results show that helping the
      family to talk about death and decision making concerning treatment can help them
      to adapt to the grieving period when the children pass away. The tactics that
      nurses can use for communication with dying children include: to acknowledge the
      decision maker in the family, adopt the concept of death appropriate to a person
      of the child's age, discuss the prognosis for the development of the disease, and
      opt to use the medium of communication. The findings of this article may serve as
      a source of reference for nurses caring for dying children, and cause greater
      attention to be paid to these issues.

PMID- 17431848
TI  - [Nurse practitioner development: from the perspective of the author].
AB  - The role of nurse practitioner (NP) has had 20 years of development in Taiwan,
      with most NPs today being trained in hospitals. The Department of Health,
      together with leaders from medical and nursing disciplines, has in recent years
      implemented laws to help ensure that NP system development remains on track.
      Numerous research studies conducted overseas verify the effectiveness of NP in
      clinical care and demonstrate that expectations of NP differ from country to
      country. As a pioneer in advanced NP training in Taiwan's higher education
      system, I believe the efficacy of NP training programs as currently organized in
      Taiwan to be equivocal. This is especially so in NP's core competency. This paper
      introduces the development of NP in Taiwan to provide better insight into the
      role and contribution of the NP training system to medical care in Taiwan.

PMID- 17431849
TI  - [Applying cognitive-behavioral therapy to a patient with schizophrenia].
AB  - The purpose of this article was to describe a nursing experience with a patient
      who suffered from delusions and hallucinations due to schizophrenia. Through
      conversation and observation, the authors gathered both subjective and objective
      data and identified two major nursing problems, as follows: altered thought
      processes and sensor/ perceptual alteration (auditory). During the nursing
      process, the authors established a rapport with the patient and provided
      cognitive-behavioral therapy to help him to reduce his irrational beliefs and
      improve his coping methods. The behavioral therapy enabled the patient to face
      his negative beliefs, and he developed cognitive-behavioral skills to improve his
      self-management of delusions and hallucinations. From this perspective, cognitive
      behavioral therapy was an effective intervention in the nursing process of caring
      for this patient with positive symptoms.

PMID- 17431850
TI  - [An experience providing terminal care based on Watson's theory to a cancer
      patient who lived alone].
AB  - This article presents the case of a terminal stage cancer patient who lived alone
      and had a detached relationship with his family, and negative behaviors such as:
      depression, passivity, silence, refusal of treatment, and inability to trust
      others because of lack of family care during hospitalization. We cared for the
      patient with direct personal nursing care, using skillful physical evaluation,
      conversation and close observation from June 11, 2004, to July 11, 2004. Using
      Watson's theory, we successfully instilled trust in the patient and developed a
      positive relationship with him. We took care of his needs in a timely manner,
      used physical care to make him feel comfortable, showed concern about what he was
      really feeling, provided him with medical information, and helped him to manage
      his physiological, psychological, social, and spiritual problems. We enabled the
      patient to face his disease, in the hope that he would experience the end of his
      life peacefully under our warm and professional nursing care.

PMID- 17431851
TI  - Analysis of a binary composite endpoint with missing data in components.
AB  - Composite endpoints are often used in clinical trials in order to increase the
      overall event rates, reduce the sizes of the trials and achieve desired power.
      For example, in a trial to study the effect of a treatment on the prevention of
      venous thromboembolic events after a major orthopaedic surgery of the lower
      limbs, the primary endpoint is usually a composite endpoint consisting of any
      deep vein thrombosis identified by systematic venography of lower limbs,
      symptomatic and well-documented non-fatal pulmonary embolism, and death from all
      causes. Just as any endpoints, missing data can occur in the components of the
      composite endpoint. If a patient has missing data on some of the components but
      not all the components, this patient may not have complete data but partial data
      for the composite endpoint. To be consistent with the intention-to-treat
      principle, the patient should not be discarded from the analysis. In this
      research, we propose an approach for the analysis of a composite endpoint with
      missing data in components. The main idea is to first derive the probabilities of
      all possible study outcomes based on the appropriate model and then to construct
      the overall rate for the composite endpoint. Simulations are conducted to compare
      the approach with several naive methods. A data example is used to illustrate the
      application of the approach.

PMID- 17431852
TI  - An extended age period cohort model for analysing (age, period)-tabulated data.
AB  - A model of an extended version of the age period cohort (APC) model is proposed
      for analysing (age, period)-tabulated data on mortality of some chronic diseases.
      Estimable functions of the parameters in the proposed model for ML estimation are
      elucidated, and the result of fitting the proposed model to the data on breast
      cancer mortality for females in the U.S. is shown, where it is seen that the
      proposed model provides a better fit to the data than APC model in terms of AIC.

PMID- 17431853
TI  - Corynebacterium diphtheriae spoligotyping based on combined use of two CRISPR
      loci.
AB  - A large diphtheria epidemic in the 1990s in Russia and neighboring countries
      underlined the importance of permanent surveillance of the circulating and
      emerging clones of Corynebacterium diphtheriae, and hence there is a need for
      highly discriminatory, simple and portable typing methods. In the complete genome
      sequence of C. diphtheriae strain NCTC13129, we previously identified in silico
      two clustered, regularly interspaced short palindromic repeat (CRISPR) loci, and
      developed a macroarray-based method to study polymorphism in the larger DRB
      locus. We named this method spoligotyping (spacer oligonucleotide typing),
      analogously to a similar method of Mycobacterium tuberculosis genotyping. Here,
      we included in the analysis novel spacers of the other CRISPR locus in C.
      diphtheriae (DRA); both loci were simultaneously co-amplified and co-hybridized
      against the membrane with 27 different immobilized spacer-probes. The use of
      additional DRA spacers improved strain differentiation and discriminated within
      large DRB clusters. The 156 Russian strains of the epidemic clone were subdivided
      into 45 combined spoligotypes compared to 35 DRB-spoligotypes and only two
      ribotypes ('Sankt-Peterburg' and 'Rossija'). The spoligotyping method allows
      digital presentation of profiles and therefore it is perfectly suitable for
      interlaboratory comparison and database management; it may become a powerful tool
      for epidemiological monitoring and phylogenetic analysis of C. diphtheriae.

PMID- 17431854
TI  - Isolation and characterization of antimicrobial proteins and peptide from chicken
      liver.
AB  - Endogenous antimicrobial peptides and proteins are crucial components of the
      innate immune system and play an essential role in the defense against infection.
      Antimicrobial activity was detected in the acid extract of livers harvested from
      healthy adult White Leghorn hens, Gallus gallus. Two antimicrobial proteins and
      one antimicrobial polypeptide were isolated from the liver extract by cation
      exchange and gel filtration chromatography, followed by two-step reverse-phase
      high-performance liquid chromatography (RP-HPLC). These antimicrobial components
      were identified as histones H2A and H2B.V, and histone H2B C-terminal fragment
      using peptide mass fingerprinting and partial sequencing by tandem
      nanoelectrospray mass spectrometry. The proteins and the peptide identified in
      the present study, which exhibited antimicrobial activity against both Gram
      positive and Gram-negative bacteria, were thermostable and showed salt-resistant
      activity. The antimicrobial properties of histones and histone fragment in
      chicken provide further evidence that histones, in addition to their role in
      nucleosome formation, may play an important role in innate host defense against
      intracellular or extracellular microbe invasion in a wide range of animal
      species.

PMID- 17431855
TI  - A new eremophilanolide from Senecio sinuatus Gilib.
AB  - From the hexane extracts of Senecio sinuatus roots, the new 3beta-angeloyloxy
      6beta-hydroxyeremophil-1(10)-en-8beta,12-olide (3), along with the known
      compounds 3beta-angeloyloxy-6beta-hydroxyeremophil-1(10)-ene (1), 3beta
      senecioyloxy-6beta-hydroxyeremophil-1(10)-ene (2), and 3beta-angeloyloxy
      6beta,8alpha-dihydroxyeremophil-1(10)-en-8beta,12-olide (4), were isolated.
      Complete 1H and 13C NMR chemical shift assignments of 1-4 were achieved using one
      and two-dimensional NMR techniques, including gHMQC and gHMBC experiments. A
      Monte Carlo search, followed by B3LYP/6-31G*DFT calculation, provided the
      theoretical conformations of the eremophilane rings, which were in agreement with
      results derived from 1H-1H NMR coupling constant analysis, and confirmed by NOESY
      experiments.

PMID- 17431856
TI  - Observation of O-H...N scalar coupling across a hydrogen bond in nocathiacin I.
AB  - We report here the observation of O-H...N hydrogen-bond (1h)J(N,OH) scalar
      coupling in a biologically active natural product. The intramolecular hydrogen
      bond between the threonine hydroxyl (Thr-OH) group and the thiazolyl nitrogen at
      the second thiazole ring (Thz-2) in nocathiacin I was directly detected by a 1H
      15N HMBC NMR experiment. The magnitude of the scalar coupling constant
      (1h)J(N,OH) was accurately measured to be 1.8 +/- 0.1 Hz by a J-resolved 1H-15N
      HMBC experiment. By adding the O-H...N distance restraint, the 3D solution
      structure of nocathiacin I was refined. The structure refinement indicated that
      the distance between the Thr-3 hydroxyl hydrogen and the Thz-2 nitrogen is
      <or=2.50 A in all the refined structures, and there are no NOE restraint
      violations >or= 0.23 A. The presence of an intramolecular hydrogen bond in
      nocathiacin I is further supported by a number of NMR parameters and additional
      NMR experiments. This observation provides valuable information for
      characterizing molecular conformations, and for studying structure-activity
      relationships.

PMID- 17431857
TI  - Studies of interactions between silane coupling agents and cellulose fibers with
      liquid and solid-state NMR.
AB  - The hydrolysis of three alkoxy-silane coupling agents, gamma-methacryloxypropyl
      trimethoxy silane (MPS), gamma-aminopropyl triethoxy silane (APS), and gamma
      diethylenetriaminopropyl trimethoxy silane (TAS), was carried out in
      ethanol/water solutions (80/20 w/w) at different pH values and followed by 1H,
      13C and 29Si NMR spectroscopy. Acidic media were found to stabilize the
      hydrolyzed forms. As expected, the formation of silanol groups was followed by
      their self-condensation to generate oligomeric structures, yielding, ultimately,
      solid homopolycondensated structures, as analyzed by 29Si and 13C high-resolution
      solid-state NMR. Hydrolyzed MPS in acidic media was then successfully adsorbed
      onto a cellulose surface and the ensuing substrates submitted to thermal
      treatment at 110-120 degrees C under reduced pressure, in order to create
      covalent bonds between cellulose and the coupling agent.

PMID- 17431858
TI  - Characterization of the malate-aluminum(III) complex using 1H and 27Al NMR
      spectroscopy.
AB  - Structural elucidation of a malate-aluminum(III) complex has been carried out
      using 1H and 27Al NMR spectroscopy. The 1H chemical shift perturbation clearly
      indicated the interaction between malate and Al(III) ion. The measurements of
      27Al NMR and 1H-13C HSQC spectra demonstrated that the major form of a complex
      comprised two equivalent malate ions and two unequivalent Al(III) ions. With this
      constraint, an equilibrium geometry of the complex was proposed by a semi
      empirical molecular orbital calculation.

PMID- 17431859
TI  - Dynamics and conformations of PEO chains chemically bonded on silica: comparison
      between 1H and 2H NMR.
AB  - 1H NMR was used to study the motion of monomer units in a layer of poly(ethylene
      oxide) chains grafted on silica. First, the dependence of the relaxation times on
      the grafting ratios is discussed qualitatively from a phenomenological point of
      view. Next, the NMR line narrowing effect by high-speed rotation is observed in
      the same samples with different grafting ratios. The magic angle spinning
      technique permits determination of two correlation times for each grafting ratio:
      tau(c) characteristic of an environment with a fast motion and tau(l)
      characteristic of an environment with a slow motion. In addition, the dynamics of
      these grafted chains are investigated by deuterium NMR (2H NMR), which is
      sensitive to the anisotropy of molecular motion. The evolution has been studied
      for two extreme grafting ratios and each time as a function of temperature. The
      anisotropy is more marked at low temperatures and for a low grafting ratio. The
      results are consistent with the 1H NMR relaxation times measured as a function of
      temperature.

PMID- 17431860
TI  - Vanadocene(IV) dicyanide complexes: the evidence super-hyperfine coupling for
      compounds with 13CN ligands.
AB  - An EPR study of the vanadocene complexes (C(5)H(5))2V(CN)2 and
      (CH(3)C(5)H(4))2V(CN)2 was carried out. Such compounds show strong super
      hyperfine coupling (|a(iso)(13C)| approximately 1.27 mT) when 13C labeled cyanide
      is used for their preparation. Super-hyperfine splitting was observed in the
      isotropic spectra of solution samples as well as in the anisotropic spectra of
      frozen solutions. Such studies were supplemented with structural characterization
      of the parent compounds. Molecular structure of the complex
      (CH(3)C(5)H(4))2V(CN)2 was determined by single-crystal X-ray diffraction
      analysis. Both compounds were characterized by infrared and Raman spectroscopy.

PMID- 17431861
TI  - Molecular mass estimation of derivatized compounds: a PFG NMR study.
AB  - Pulsed-field gradient (PFG) 1H and 31P NMR methods were developed to
      quantitatively estimate the molecular mass of compounds, derivatized with either
      trichloroacetyl isocyanate (TAI) or 2-chloro-4,4,5,5-tetramethyl-1,3,2
      dioxaphospholane (chlorophospholane). These agents provide selective analysis
      with high sensitivity for molecules containing alcohol, amine, carboxylic acid,
      or thiol functional groups. Tetramethylsilane (TMS) or bisphenol A was used as
      internal diffusion reference. The empirical relationship between relative
      diffusivity and molecular mass was established for a set of mono- and
      difunctional compounds with molecular masses in the range 32-330 g/mol. The
      utility of the method was demonstrated by analyzing alcohol, phenol, and
      carboxylic acid components in lubricating oil.

PMID- 17431862
TI  - Cucurbitane triterpenoids from Momordica charantia.
AB  - Three new cucurbitane-type triterpenoid saponins, 23-O-beta-D-allopyranosyl
      5beta,19-epoxycucurbita-6,24-diene-3beta,22(S),23(S)-triol-3-O-beta-D
      glucopyranoside (1), 23-O-beta-D-allopyranosyl-5beta,19-epoxycucurbita-6,24-diene
      3beta,22(S),23(S)-triol-3-O-beta-D-allopyranoside (2), and 23-O-beta-D
      allopyranosyl-5beta,19-epoxycucurbita-6,24-diene-3beta,19(R), 22(S),23(S)-tetraol
      3-O-beta-D-allopyranoside (3), named momordicoside M, N, and O, respectively,
      along with one known saponin momordicoside L (4), were isolated from the fresh
      fruits of Momordica charantia. The structures of these saponins were elucidated
      on the basis of chemical properties and spectral data.

PMID- 17431863
TI  - Synthesis of highly functionalized chiral cyclopentanes by catalytic enantio- and
      diastereoselective double Michael addition reactions.

PMID- 17431864
TI  - Synthesis and structure of a cationic platinum borylene complex.

PMID- 17431865
TI  - Asymmetric bioreduction of activated alkenes using cloned 12-oxophytodienoate
      reductase isoenzymes OPR-1 and OPR-3 from Lycopersicon esculentum (tomato): a
      striking change of stereoselectivity.

PMID- 17431866
TI  - Effects of chain length and N-methylation on a cation-pi interaction in a beta
      hairpin peptide.
AB  - The effects of N-methylation and chain length on a cation-pi interaction have
      been investigated within the context of a beta-hairpin peptide. Significant
      enhancement of the interaction and structural stabilization of the hairpin have
      been observed upon Lys methylation. Thermodynamic analysis indicates an increased
      entropic driving force for folding upon methylation of Lys residues. Comparison
      of lysine to analogues ornithine (Orn) and diaminobutyric acid (Dab) indicates
      that lysine provides the strongest cation-pi interaction and also provides the
      most stable beta-hairpin due to a combination of side chain-side chain
      interactions and beta-sheet propensities. These studies have significance for the
      recognition of methylated lysine in histone proteins.

PMID- 17431867
TI  - Enzyme-catalysed synthesis and absolute configuration assignments of cis
      dihydrodiol metabolites from 1,4-disubstituted benzenes.
AB  - A series of ten cis-dihydrodiol metabolites has been obtained by bacterial
      biotransformation of the corresponding 1,4-disubstituted benzene substrates using
      Pseudomonas putida UV4, a source of toluene dioxygenase (TDO). Their enantiomeric
      excess (ee) values have been established using chiral stationary phase HPLC and
      1H NMR spectroscopy. Absolute configurations of the majority of cis-dihydrodiols
      have been established using stereochemical correlation and X-ray crystallography
      and the remainder have been tentatively assigned using NMR spectroscopic methods
      but finally confirmed by circular dichroism (CD) spectroscopy. These
      configurational assignments support and extend the validity of an empirical
      model, previously used to predict the preferred stereochemistry of TDO-catalysed
      cis-dihydroxylation of ten 1,4-disubstituted benzene substrates, to more than
      twenty-five examples.

PMID- 17431868
TI  - Double aromaticity in monocyclic carbon, boron, and borocarbon rings based on
      magnetic criteria.
AB  - The double-aromatic character of selected monocyclic carbon, boron, and
      borocarbon rings is demonstrated by refined nucleus-independent chemical shift
      (NICS) analyses involving the contributions of individual canonical MOs and their
      out-of-plane NICS tensor component (CMO-NICS(zz)). The double aromaticity
      considered results from two mutually orthogonal Huckel p AO frameworks in a
      single molecule. The familiar pi orbitals are augmented by the in-plane
      delocalization of electrons occupying sets of radial (rad) p orbitals. Such
      double aromaticity is present in B(3) (-), C(6)H(3) (+), C(6) (4+), C(4)B(4)
      (4+), C(6), C(5)B(2), C(4)B(4), C(2)B(8), B(10) (2-), B(12), C(10), C(9)B(2),
      C(8)B(4), C(7)B(6), C(6)B(8), and C(14). Monocyclic C(8) and C(12) are doubly
      antiaromatic, as both the orthogonal pi and radial Huckel sets are paratropic.
      Planar C(7) and C(9) monocycles have mixed aromatic (pi) and antiaromatic
      (radial) systems.

PMID- 17431869
TI  - Ligand reprogramming in dinuclear helicate complexes: a consequence of allosteric
      or electrostatic effects?
AB  - The ditopic ligand 6,6'-bis(4-methylthiazol-2-yl)-3,3'-([18]crown-6)-2,2'
      bipyridine (L(1)) contains both a potentially tetradentate pyridyl-thiazole (py
      tz) N-donor chain and an additional "external" crown ether binding site which
      spans the central 2,2'-bipyridine unit. In polar solvents (MeCN, MeNO(2)) this
      ligand forms complexes with Zn(II), Cd(II), Hg(II) and Cu(I) ions via
      coordination of the N donors to the metal ion. Reaction with both Hg(II) and
      Cu(I) ions results in the self-assembly of dinuclear double-stranded helicate
      complexes. The ligands are partitioned by rotation about the central py--py bond,
      such that each can coordinate to both metals as a bis-bidentate donor ligand.
      With Zn(II) ions a single-stranded mononuclear species is formed in which one
      ligand coordinates the metal ion in a planar tetradentate fashion. Reaction with
      Cd(II) ions gives rise to an equilibrium between both the dinuclear double
      stranded helicate and the mononuclear species. These complexes can further
      coordinate s-block metal cations via the remote crown ether O-donor domains; a
      consequence of which are some remarkable changes in the binding modes of the N
      donor domains. Reaction of the Hg(II)- or Cd(II)-containing helicate with either
      Ba(2+) or Sr(2+) ions effectively reprogrammes the ligand to form only the single
      stranded heterobinuclear complexes [MM'(L(1))](4+) (M=Hg(II), Cd(II); M'=Ba(2+),
      Sr(2+)), where the transition and s-block cations reside in the N- and O-donor
      sites, respectively. In contrast, the same ions have only a minor structural
      impact on the Zn(II) species, which already exists as a single-stranded
      mononuclear complex. Similar reactions with the Cd(II) system result in a shift
      in equilibrium towards the single-stranded species, the extent of which depends
      on the size and charge of the s-block cation in question. Reaction of the
      dicopper(I) double-stranded helicate with Ba(2+) shows that the dinuclear
      structure still remains intact but the pitch length is significantly increased.

PMID- 17431870
TI  - A "green route" to propene through selective hydrogen oxidation.
AB  - The pros and cons of oxidative dehydrogenation of propane are outlined and a new
      catalytic system based on metal-doped cerianite catalysts is introduced. These
      novel materials catalyze the selective combustion of hydrogen from a mixture of
      hydrogen, propane, and propene at 550 degrees C. This gives three key advantages:
      energy is supplied directly where needed, product separation is made easier, and
      the dehydrogenation equilibrium is shifted to the desired products. A set of
      eighteen doped cerianites was synthesized in parallel, characterized, and
      screened for activity, selectivity, and stability in a cyclic redox system. The
      best results were obtained with Ce(0.89)Cr(0.02)Fe(0.09)O(2),
      Ce(0.98)Sn(0.02)O(2), and Ce(0.96)Cu(0.02)Zn(0.02)O(2), which gave 98 %, 91 %,
      and 98 % selectivity, respectively. Ce(0.89)Cr(0.02)Fe(0.09)O(2) also shows
      excellent stability in over 120 cycles (66 h on stream at 550 degrees C).
      Importantly, these doped cerias are monophasic crystalline materials. The dopants
      are incorporated as solid solutions throughout the fluorite lattice. This means
      that these catalysts are very stable (they do not sinter during reduction) as
      opposed to traditional supported metal oxides. The results show that both
      activity and selectivity towards hydrogen combustion can be tuned (increased or
      decreased) by selecting the appropriate dopant. Furthermore, the trends in
      selectivity differ from those measured on supported oxides of the same elements,
      which indicates that these novel materials indeed contain unique active sites.
      The factors governing selectivity towards hydrogen oxidation and the nature of
      the active site are discussed.

PMID- 17431871
TI  - Construction of an aryliridium-salen complex for highly cis- and enantioselective
      cyclopropanations.

PMID- 17431875
TI  - Systematic comparison of perfusion-CT and CT-angiography in acute stroke
      patients.
AB  - OBJECTIVE: To systematically evaluate the accuracy of noncontrast computed
      tomography (NCT), perfusion computed tomography (PCT), and computed tomographic
      angiography (CTA) in determining site of occlusion, infarct core, salvageable
      brain tissue, and collateral flow in a large series of patients suspected of
      acute stroke. METHODS: We retrospectively identified all consecutive patients
      with signs and symptoms suggesting hemispheric stroke of < 48 hours in duration
      who were evaluated on admission by NCT, PCT, and CTA, and underwent a follow-up
      CT/CTA or magnetic resonance imaging (MRI) and magnetic resonance angiography
      (MRA) within 6 months of initial imaging. Two neuroradiologists evaluated NCT for
      hypodensity, PCT for infarct core and salvageable brain tissue, and CTA source
      images and maximal intensity projections for site of occlusion, infarct core, and
      collateral flow. Follow-up CTA and MRA were assessed for persistent arterial
      occlusion or recanalization. Follow-up CT and MRI were reviewed for final infarct
      location and volume, and used as a gold standard to calculate sensitivity (SE)
      and specificity (SP) of initial imaging. RESULTS: A total of 113 patients were
      considered for analysis, including 55 patients with a final diagnosis of stroke.
      CTA source images were the most accurate technique in the detection of the site
      of occlusion (SE = 95%; SP = 100%). Decreased cerebral blood volume on PCT was
      the most accurate predictor of final infarct volume (SE = 80%; SP = 97%),
      Increased mean transit time on PCT was predictive of the tissue at risk for
      infarction in patients with persistent arterial occlusion. CTA maximal intensity
      projections was the best technique to quantify the degree of collateral
      circulation. INTERPRETATION: The most accurate assessment of the site of
      occlusion, infarct core, salvageable brain tissue, and collateral circulation in
      patients suspected of acute stroke is afforded by a combination of PCT and CTA.

PMID- 17431876
TI  - Retinal vessel diameters and the role of inflammation in cerebrovascular disease.
AB  - Retinal vessels may provide a way to study the cerebral microcirculation. In
      particular, larger retinal venular diameters have been associated with
      cerebrovascular disease. An inflammatory response may underlie this association.
      In a population-based cohort study among 5,279 participants aged 55 years or
      older with graded retinal vessel diameters, we observed that greater serum levels
      of C-reactive protein and fibrinogen and greater lipoprotein-associated
      phospholipase A(2) activity were strongly associated with larger venular
      diameters. Weaker associations were found with arteriolar diameters. Our findings
      support the hypothesis that larger retinal venular diameters reflect systemic
      inflammation and suggest that inflammation is involved in cerebrovascular
      disease.

PMID- 17431877
TI  - Rapid high-resolution karyotyping with precise identification of chromosome
      breakpoints.
AB  - Many techniques have been developed in recent years for genome-wide analysis of
      genetic alterations, but no current approach is capable of rapidly identifying
      all chromosome rearrangements with precise definition of breakpoints. Combining
      multiple color fluorescent in situ hybridization and high-density single
      nucleotide polymorphism array analyses, we present here an approach for high
      resolution karyotyping and fast identification of chromosome breakpoints. We
      characterized all of the chromosome amplifications and deletions, and most of the
      chromosome translocation breakpoints of three prostate cancer cell lines at a
      resolution which can be further analyzed by sequence-based techniques. Genes at
      the breakpoints were readily determined and potentially fused genes identified.
      Using high-density exon arrays we simultaneously confirmed altered exon
      expression patterns in many of these breakpoint genes.

PMID- 17431879
TI  - Professor Nina Berova--winner of 2007 Chirality Medal.

PMID- 17431878
TI  - Specific extra chromosomes occur in a modal number dependent pattern in pediatric
      acute lymphoblastic leukemia.
AB  - Children with acute lymphoblastic leukemia (ALL) and high hyperdiploidy (>50
      chromosomes) are considered to have a relatively good prognosis. The specific
      extra chromosomes are not random; extra copies of some chromosomes occur more
      frequently than those of others. We examined the extra chromosomes present in
      high hyperdiploid ALL to determine if there were a relation of the specific extra
      chromosomes and modal number (MN) and if the extra chromosomes present could
      differentiate high hyperdiploid from near-triploid and near-tetraploid cases.
      Karyotypes of 2,339 children with ALL and high hyperdiploidy at diagnosis showed
      a distinct nonrandom sequential pattern of gain for each chromosome as MN
      increased, with four groups of gain: chromosomes 21, X, 14, 6, 18, 4, 17, and 10
      at MN 51-54; chromosomes 8, 5, 11, and 12 at MN 57-60; chromosomes 2, 3, 9,16,
      and 22 at MN 63-67; chromosomes 1, 7 13, 15, 19, and 20 at MN 68-79, and Y only
      at MN >or=80. Chromosomes gained at lower MN were retained as the MN increased.
      High hyperdiploid pediatric ALL results from a single abnormal mitotic division.
      Our results suggest that the abnormal mitosis involves specific chromosomes
      dependent on the number of chromosomes aberrantly distributed, raising
      provocative questions regarding the mitotic mechanism. The patterns of
      frequencies of tetrasomy of specific chromosomes differs from that of trisomies
      with the exception of chromosome 21, which is tetrasomic in a high frequency of
      cases at all MN. These results are consistent with different origins of high
      hyperdiploidy, near-trisomy, and near-tetrasomy.

PMID- 17431880
TI  - Functional profiling of uncommon VCAM1 promoter polymorphisms prevalent in
      African American populations.
AB  - Multiple variants of the vascular adhesion molecule-1 (VCAM1) promoter show
      increased nucleotide heterozygosity in the African American population. Using a
      novel transfection-based transcriptional pathway profiling method, we show that
      select uncommon variants are functionally hyperactive. Eight candidate VCAM1
      promoter haplotypes comprising 13 previously identified SNPs were assessed for
      response to known mitogens. Activity was correlated with bioinformatic analysis
      of hyper- and hyporesponsive variants to identify the gain or loss of haplotype
      specific transcription factor binding site (TFBS). Using this approach, a low
      frequency regulatory allele (c.-540A>G; dbSNP rs3783605:A>G), found in a
      hyperactive VCAM1 promoter haplotype, was shown to create a candidate binding
      site for ETS2 that was confirmed in vivo by chromatin immunoprecipitation. This
      report provides the first functional evaluation of VCAM1 promoter polymorphisms
      and establishes a hypothetical foundation for investigation of their role in the
      pathogenesis of VCAM1-associated diseases that disproportionately afflict African
      Americans, including thromboembolic diseases, asthma, and multiple myeloma.

PMID- 17431881
TI  - Frequency of new or worsening symptoms in the posthospitalization period.
AB  - BACKGROUND: When patients are discharged from the hospital, they are assumed to
      be stable until follow-up as outpatients. OBJECTIVE: To study the frequency of
      new or worsening symptoms within 2-5 days of hospital discharge. DESIGN:
      Retrospective analysis of data from telephone calls to patients by centralized
      call center. SETTING: Patients discharged by hospitalists employed by IPC-The
      Hospitalist Company. PATIENTS: 15,767 patients surveyed between May 1, 2003, and
      October 31, 2003. INTERVENTION: Patients discharged home were contacted by a
      central call center in the first several days after discharge. MEASUREMENTS:
      Patient demographics, self-rated health status, prevalence of new or worsening
      symptoms, medication issues, home health services issues, and status of scheduled
      follow-up appointments. RESULTS: Of the patients surveyed, 11.9% reported new or
      worsening symptoms since leaving the hospital. There were no differences by age.
      Women were more likely than men to be symptomatic. Patients with worse health
      status were more likely to have new or worse symptoms (P < .0001). Symptomatic
      patients were minimally more likely to have made a follow-up appointment (61.0%
      vs. 58.4%, P < .05) and were more likely to have medication issues (22.2% vs.
      6.8%, P < .0001) and problems with receiving home health care services (5.8% vs.
      3.6%, P < .05). CONCLUSIONS: A significant percentage of patients had new or
      worsening symptoms in the first several days after discharge. These patients were
      only minimally more likely to have made follow-up appointments. A system to
      manage the postdischarge transition period is essential to improving
      posthospitalization outcomes.

PMID- 17431882
TI  - Clinical and mutational profile in spinal muscular atrophy with respiratory
      distress (SMARD): defining novel phenotypes through hierarchical cluster
      analysis.
AB  - Autosomal recessive spinal muscular atrophy with respiratory distress (SMARD) is
      a heterogeneous disorder. Mutations in the immunoglobulin micro-binding protein
      gene (IGHMBP2) lead to SMARD1, but clinical criteria that delineate SMARD1 from
      other SMARD syndromes are not well established. Here we present a retrospective
      clinical and genetic study to determine the criteria that would predict the
      presence or absence of IGHMBP2 mutations. From 141 patients with respiratory
      distress and a spinal muscular atrophy phenotype we recorded the clinical
      features through a questionnaire and sequenced the entire coding region of
      IGHMBP2. In 47 (33%) patients we identified IGHMBP2 mutations, 14 of which were
      not described before. Clinical features and combinations thereof associated with
      the presence of IGHMBP2 mutations were discovered through hierarchical cluster
      analysis. This method detects common traits not evident at first sight by
      grouping items according to their similarity. The combination of "manifestation
      of respiratory failure between 6 weeks and 6 months" AND ("presence of
      diaphragmatic eventration" OR "preterm birth") predicted the presence of IGHMBP2
      mutations with 98% sensitivity and 92% specificity. Non-SMARD1 patients fell into
      two different symptom clusters, mainly separated by the age at respiratory
      failure and the presence of multiple congenital contractures. The 14 novel
      IGHMBP2 mutations comprised missense, frameshift, splice-site, and nonsense
      mutations. All missense mutations altered conserved residues within or adjacent
      to the putative DNA helicase domain. The c.1235+3A>G splice-site mutation did not
      entirely suppress correct splicing and we found a residual wild-type IGHMBP2 mRNA
      steady-state level of 24.4+/-6.9%, which was, however, not sufficient to avert
      SMARD1 in this patient.

PMID- 17431883
TI  - Comparison of RNA yield from small cell populations sorted by flow cytometry
      applying different isolation procedures.
AB  - BACKGROUND: RNA from sorted cell populations is crucial in many instances. We
      therefore compared four current protocols for RNA isolation, with regard to mRNA
      yield and purity. Moreover, we examined the effects on RNA recovery caused by
      different storage reagents. METHODS: Small populations of K562 cells or PMBC were
      sorted into the lysing reagent and subjected to RNA extraction, employing either
      phase separation extraction using an acidic guanidinium-isothiocyanate reagent
      (TriFast reagent), the silica-gel membrane-based spin-column technology (RNeasy
      Mini-/Micro-Kit), or the isolation via paramagnetic oligo(d)T-beads (microMACS).
      Cells designated for delayed RNA isolation were kept either in RNAlater, Qiagen
      Buffer RLT, TriFast or PrepProtect, or simply frozen after pelleting from PBS.
      The mRNA yield was determined by quantitative RT-PCR. RESULTS: Performing
      unpaired two-tailed t-tests revealed that RNA was extracted in significantly
      higher amounts using magnetic bead isolation. This method also allowed best
      discrimination of induced IL2 gene expression. In contrast, phase separation
      extraction showed the highest rate of failures. Intermediate storage reduced RNA
      yield. Contamination by genomic DNA was detected in several samples subjected to
      phase separation or silica-gel membrane-based spin-column extraction.
      CONCLUSIONS: Our results reveal advantages and disadvantages of RNA isolation
      procedures for small numbers of sorted cells and, therefore, facilitate the
      decision for the most appropriate protocol in a particular experimental context.

PMID- 17431884
TI  - Detection of molecular particles in live cells via machine learning.
AB  - Clathrin-coated pits play an important role in removing proteins and lipids from
      the plasma membrane and transporting them to the endosomal compartment. It is,
      however, still unclear whether there exist "hot spots" for the formation of
      Clathrin-coated pits or the pits and arrays formed randomly on the plasma
      membrane. To answer this question, first of all, many hundreds of individual pits
      need to be detected accurately and separated in live-cell microscope movies to
      capture and monitor how pits and vesicles were formed. Because of the noisy
      background and the low contrast of the live-cell movies, the existing image
      analysis methods, such as single threshold, edge detection, and morphological
      operation, cannot be used. Thus, this paper proposes a machine learning method,
      which is based on Haar features, to detect the particle's position. Results show
      that this method can successfully detect most of particles in the image. In order
      to get the accurate boundaries of these particles, several post-processing
      methods are applied and signal-to-noise ratio analysis is also performed to rule
      out the weak spots.

PMID- 17431885
TI  - Depression and breastfeeding: which postpartum patients take antidepressant
      medications?
AB  - Depressed breastfeeding women may have concerns about taking antidepressant
      medications due to fears regarding infant exposure. We examined the clinical
      records of 73 breastfeeding women who sought depression treatment, to identify
      characteristics of those who took antidepressants. Compared to women who were not
      treated with pharmacotherapy, breastfeeding patients who took antidepressants had
      more severe symptoms, greater functional impairment, more extensive psychiatric
      histories, and were less likely to be involved in a committed relationship. No
      differences were found in age, race, or education.

PMID- 17431886
TI  - Modulating testosterone stimulated prostate growth by phenethyl isothiocyanate
      via Sp1 and androgen receptor down-regulation.
AB  - BACKGROUND: The effects of phenethyl isothiocyanate (PEITC), present naturally in
      cruciferous vegetables, on androgen-influenced growth of the prostate such as
      benign hyperplasia, was investigated. METHODS: Rats dosed with cyproterone
      acetate and testosterone, were fed at the same time with either PEITC or vehicle
      control. The growth of the prostates was compared to untreated rats. RESULTS:
      While testosterone increased the prostate mass (30%) and hyperplastic
      seminiferous tubules as compared to the untreated rats, PEITC feeding decreased
      the prostate mass and hyperplasia to roughly the levels of untreated rats (P <
      0.05). PEITC negated the testosterone-mediated enhancement of the androgen
      receptor (AR), via down-regulating transcription factor Sp1 expression and Sp1
      binding complex formation. Cell cycle progression was attenuated with decreases
      of cyclins, Rb, and up-regulates p27. CONCLUSIONS: PEITC modulates the
      testosterone-influenced growth by repressing Sp1, thus down-regulating AR and
      proliferation. PEITC from cruciferous vegetables may represent a regulator for
      hormone-dependent growth of the prostate.

PMID- 17431887
TI  - Current and emerging treatment options in chronic myeloid leukemia.
AB  - Treatments for chronic myeloid leukemia (CML) represent a success story in
      molecular medicine. The development of imatinib, a tyrosine kinase inhibitor
      (TKI) targeted against the causative Bcr-Abl oncoprotein in CML, has resulted in
      hematologic and cytogenetic remissions in all phases of CML. A significant
      proportion of patients are resistant to imatinib or develop resistance during
      treatment. This is often a result of mutated forms of the Bcr-Abl oncoprotein to
      which imatinib is unable to bind. Several strategies have been developed to
      overcome the problem of imatinib resistance, including high-dose imatinib, novel
      targeted agents, and combination treatments. Novel agents include dasatinib, a
      potent TKI that inhibits several critical oncogenic proteins and which has
      recently been approved for patients with CML who are resistant or intolerant to
      imatinib; and nilotinib, a potent selective Bcr-Abl kinase inhibitor currently in
      clinical development. Other agents in development include SKI-606 and INNO-406.
      Stem cell transplantation remains a useful option, although it is not generally
      used as first-line treatment. Overall, there are an increasing number of
      treatment options available for patients with CML.

PMID- 17431888
TI  - Re: Timing of adjuvant chemotherapy initiation after surgery for stage III colon
      cancer.

PMID- 17431891
TI  - Temperature induced denaturation of collagen in acidic solution.
AB  - The denaturation of collagen solution in acetic acid has been investigated by
      using ultra-sensitive differential scanning calorimetry (US-DSC), circular
      dichroism (CD), and laser light scattering (LLS). US-DSC measurements reveal that
      the collagen exhibits a bimodal transition, i.e., there exists a shoulder
      transition before the major transition. Such a shoulder transition can recover
      from a cooling when the collagen is heated to a temperature below 35 degrees C.
      However, when the heating temperature is above 37 degrees C, both the shoulder
      and major transitions are irreversible. CD measurements demonstrate the content
      of triple helix slowly decreases with temperature at a temperature below 35
      degrees C, but it drastically decreases at a higher temperature. Our experiments
      suggest that the shoulder transition and major transition arise from the
      defibrillation and denaturation of collagen, respectively. LLS measurements show
      the average hydrodynamic radius R(h), radius of gyration R(g)of the collagen
      gradually decrease before a sharp decrease at a higher temperature. Meanwhile,
      the ratio R(g)/R(h) gradually increases at a temperature below approximately 34
      degrees C and drastically increases in the range 34-40 degrees C, further
      indicating the defibrillation of collagen before the denaturation.

PMID- 17431892
TI  - Skewed X-chromosome inactivation is associated with primary but not secondary
      ovarian failure.
AB  - Premature ovarian failure (POF) is the occurrence of menopause before the age of
      40, and may present with either primary or secondary amenorrhea. Numerous cases
      of POF in women with X-chromosome deletions or translocations have been reported;
      thus, it is possible that smaller rearrangements undetectable by conventional
      cytogenetics may contribute to POF in some patients. In females with an abnormal
      X chromosome, cells with inactivation of the normal X may be selected against,
      causing skewed X-chromosome inactivation (XCI). We therefore assessed XCI by
      methylation sensitive restriction digestion and PCR amplification at the androgen
      receptor (AR) locus, in 4 primary and 55 secondary POF patients and 109 control
      women. In samples heterozygous at AR and therefore informative for the skewing
      assay, the frequency of skewed XCI among the women with secondary amenorrhea was
      identical to that in control women, with 4 out of 48 (8.3%) secondary ovarian
      failure patients and 8 out of 97 (8.2%) control women having > or =90% skewing.
      Notably, all three primary amenorrhea patients that were informative at AR had
      skewed XCI > or =90% (P = 0.001 vs. control women; Fisher's exact test). To
      investigate whether X-chromosome copy number alterations were responsible, DNA
      from selected patients with skewed XCI was examined by high resolution DNA
      microarray, however no potential regions of DNA addition or deletion were
      confirmed by FISH or PCR. X-chromosome abnormalities undetectable by array, or
      reduced follicular pool due to an early trisomic rescue event, may explain the
      skewed XCI observed in POF patients presenting with primary amenorrhea.

PMID- 17431893
TI  - The first 4p euchromatic variant in a healthy carrier having an unusual
      reproductive history.
AB  - We report on the molecular cytogenetics studies in a healthy couple who had had
      three pregnancies which ended in a termination of pregnancy (TOP). In two of
      them, prenatal sonogram showed fetal dwarfism and in the third one, a chromosome
      alteration was found in the amniocentesis. A previous pregnancy ended in a
      healthy girl. A high-resolution G-band karyotype (550-850 bands), together with
      Fluorescence in situ Hybridization (FISH) techniques, detected in the father a 4p
      interstitial euchromatic duplication. This chromosome duplication appears to be a
      previously undescribed euchromatic variant (EV). We discuss the possibility that
      the 4p paternal EV could be involved in the clinical and genetic findings of the
      three TOPs.

PMID- 17431894
TI  - Hyperhomocysteinemia and MTHFR polymorphisms in association with orofacial clefts
      and congenital heart defects: a meta-analysis.
AB  - Several studies have reported an association between hyperhomocysteinemia, 5,10
      methylenetetrahydrofolate reductase (MTHFR) polymorphisms and cleft lip with or
      without cleft palate (CLP), and congenital heart defects (CHDs). However,
      findings have been inconsistent. A meta-analysis was performed of published
      studies until September 2006 investigating these associations in both mothers and
      children. Homocysteine data were provided in two CLP and three CHD studies, and
      MTHFR polymorphisms were reported in ten CLP and eight CHD studies. Data were
      analyzed using the random effects model in the Cochrane Review Manager. The
      pooled odds ratio (OR) of maternal hyperhomocysteinemia was 2.3 (95% CI 0.4-11.9)
      for CLP, and 4.4 (2.6-7.3) for CHDs. The MTHFR C677T polymorphism and CLP showed
      pooled ORs of 1.2 (0.9-1.5) in mothers and 1.0 (0.9-1.2) in children, whereas
      these estimates for the A1298C polymorphism were 1.0 (0.7-1.2) in mothers and 0.9
      (0.6-1.2) in children. The MTHFR C677T polymorphism in CHD studies demonstrated a
      pooled OR of 1.0 (0.8-1.3) for mothers and 1.1 (0.9-1.5) for children. Two
      studies investigating the maternal A1298C polymorphism in CHDs demonstrated a
      pooled OR of 1.2 (0.8-1.8). Only one CHD study reported an OR of 1.3 (0.8-2.1)
      for this polymorphism in children. In conclusion, this meta-analysis demonstrates
      that maternal hyperhomocysteinemia is a risk factor for CHDs. The MTHFR
      polymorphisms C677T and A1298C in both mothers and children are not independently
      associated with CLP or CHDs. Future studies should be performed to investigate
      the interactions between maternal hyperhomocysteinemia, B-vitamin intake, related
      polymorphisms and the risk of CLP and CHDs.

PMID- 17431895
TI  - Smith-Magenis syndrome and Moyamoya disease in a patient with
      del(17)(p11.2p13.1).
AB  - Chromosomal rearrangements causing microdeletions and microduplications are a
      major cause of congenital malformation and mental retardation. Because they are
      not visible by routine chromosome analysis, high resolution whole-genome
      technologies are required for the detection and diagnosis of small chromosomal
      abnormalities. Recently, array-comparative genomic hybridization (aCGH) and
      multiplex ligation-dependent probe amplification (MLPA) have been useful tools
      for the identification and mapping of deletions and duplications at higher
      resolution and throughput. Smith-Magenis syndrome (SMS) is a multiple congenital
      anomalies/mental retardation syndrome caused by deletion or mutation of the
      retinoic acid induced 1 (RAI1) gene and is often associated with a chromosome
      17p11.2 deletion. We report here on the clinical and molecular analysis of a 10
      year-old girl with SMS and moyamoya disease (occlusion of the circle of Willis).
      We have employed a combination of aCGH, FISH, and MLPA to characterize an
      approximately 6.3 Mb deletion spanning chromosome region 17p11.2-p13.1 in this
      patient, with the proximal breakpoint within the RAI1 gene. Further,
      investigation of the genomic architecture at the breakpoint intervals of this
      large deletion documented the presence of palindromic repeat elements that could
      potentially form recombination substrates leading to unequal crossover.

PMID- 17431896
TI  - On the spectrum of limb-body wall complex, exstrophy of the cloaca, and urorectal
      septum malformation sequence.
AB  - The limb-body wall complex (LBWC) is characterized by abdominal wall and limb
      defects, exstrophy of the cloaca (EC) by lack of closure of the lower abdominal
      wall and lack of cloacal septation, and the urorectal septum malformation
      sequence (URSMS) by absent perineal and anal openings, ambiguous genitalia,
      colonic, and renal anomalies. We report here on three fetuses whom have
      overlapping features of these disorders. Also we have reviewed the literature for
      cases with overlapping features of two or three of the above conditions. From the
      description of the cases reported on here and those in the literature, we propose
      that the overlap of features found among LBWC, EC, and URSMS represent a
      continuous spectrum of abnormalities, rather than three separate conditions. As
      such, we suggest that all three conditions may share a common etiology or
      pathogenetic mechanism.

PMID- 17431897
TI  - Pituitary abnormalities in Prader-Willi syndrome and early onset morbid obesity.
AB  - Prader-Willi syndrome (PWS) is a well-defined syndrome of childhood-obesity which
      can serve as a model for investigating early onset childhood obesity. Many of the
      clinical features of PWS (e.g., hyperphagia, hypogonadotropic hypogonadism,
      growth hormone deficiency) are hypothesized to be due to abnormalities of the
      hypothalamus and/or pituitary gland. Children who become severely obese very
      early in life (i.e., before age 4 years) may also have a genetic etiology of
      their obesity, perhaps with associated neuroendocrine and hypothalamo-pituitary
      defects, as infants and very young children have limited access to environmental
      factors that contribute to obesity. We hypothesized that morphologic
      abnormalities of the pituitary gland would be seen in both individuals with PWS
      and other subjects with early onset morbid obesity (EMO). This case-control study
      included individuals with PWS (n = 27, age 3 months to 39 years), patients with
      EMO of unknown etiology (n = 16, age 4-22 years; defined as body mass index
      greater than the 97th centile for age before age 4 years), and normal weight
      siblings (n = 25, age 7 months to 43 years) from both groups. Participants had 3
      dimensional magnetic resonance imaging to evaluate the pituitary gland, a
      complete history and physical examination, and measurement of basal pituitary
      hormones. Subjects with PWS and EMO had a higher prevalence of pituitary
      morphological abnormalities than did control subjects (74% PWS, 69% EMO, 8%
      controls; P < 0.001). Anterior pituitary hormone deficiencies were universal in
      individuals with PWS (low IGF-1 in 100%, P < 0.001 PWS vs. controls; central
      hypothyroidism in 19%, P = 0.052, and hypoplastic genitalia or hypogonadotropic
      hypogonadism in 100%, P < 0.001), and was often seen in individuals with EMO (6%,
      P = 0.89 vs. control, 31%, P = 0.002, and 25%, P = 0.018, respectively). The
      presence of a hypoplastic pituitary gland appeared to correlate with the presence
      of anterior pituitary hormone deficiencies in individuals with EMO, but no
      correlation was apparent in individuals with PWS. In conclusion, the high
      frequency of both morphological and hormonal abnormalities of the pituitary gland
      in both individuals with PWS and EMO suggests that abnormalities in the
      hypothalamo-pituitary axis are features not only of PWS, but also frequently of
      EMO of unknown etiology.

PMID- 17431899
TI  - Re: folate gene polymorphisms and the risk of Down syndrome pregnancies in young
      Italian women.

PMID- 17431898
TI  - Ovotestes and XY sex reversal in a female with an interstitial 9q33.3-q34.1
      deletion encompassing NR5A1 and LMX1B causing features of Genitopatellar
      syndrome.
AB  - We describe our findings in a 46,XY female with a clinical features of
      Genitopatellar syndrome (GPS) and confirmed hermaphroditism with ovotestes, and
      five additional patients with GPS. GPS is a genetic disorder characterized by
      renal and genital anomalies, joint dislocation, aplastic or hypoplastic and often
      displaced patellae, minor facial anomalies, and mental retardation. The genital
      anomalies clearly distinguish GPS from nail-patella syndrome (NPS) that has
      similar features, but additionally shows hypoplastic finger- and toenails as
      found in the 46,XY female. In our patients no mutation was found in the coding
      regions of WNT4, WNT7A, TBX4, and LMX1B. Fluorescent in situ hybridization (FISH)
      and array-based comparative genome hybridization (aCGH) analysis showed a 3 Mb
      deletion of LMX1B, NR6A1, and NR5A1 (SF1) in the 46,XY female. This is the first
      report of a microdeletion causing haploinsuffiency of LMX1B and NR5A1. The
      deletion of LMX1B is responsible for the knee anomalies and the deletion of NR5A1
      likely causes the sex reversal. Cytogenetic analysis of the five additional
      patients with diagnosed GPS failed to identify a similar microdeletion, or
      inversion of a potentially regulatory element between the two genes. This
      suggests that the locus 9q33-9q34 can be excluded for GPS and that the presented
      case is unique in its combination of GPS and NPS features caused by a
      microdeletion associated with loss of function of LMX1B and NR5A1.

PMID- 17431900
TI  - Identification of a novel recessive RELN mutation using a homozygous balanced
      reciprocal translocation.
AB  - Two siblings from a consanguineous Egyptian marriage showed an identical
      phenotype of cortical lissencephaly with cerebellar hypoplasia, severe epilepsy,
      and mental retardation. Examination of karyotype revealed 46, t(7;12)(q22;p13)mat
      (7;12)(q22;p13)pat in both affected children, suggesting a homozygous reciprocal
      balanced translocation. Each healthy parent was a carrier of the balanced
      translocation in the heterozygous state, suggesting homozygous disruption of a
      gene involved in brain development. There were early spontaneous abortions in
      this family, as would be expected from transmission of an unbalanced chromosome.
      A disruption of RELN at 7q22.1 with absence of encoded protein was identified.
      This is the first demonstration that such rare homozygous translocations can be
      used to identify recessive disease gene mutations.

PMID- 17431901
TI  - Dandy-Walker complex in a boy with a 5 Mb deletion of region 1q44 due to a
      paternal t(1;20)(q44;q13.33).
AB  - A 10-year-old boy with vermis hypoplasia, dilatation of the fourth ventricle,
      enlarged cisterna magna and aplasia of the corpus callosum, consistent with the
      Dandy-Walker complex (DWC), and slight facial dysmorphisms, severe motor and
      mental retardation is presented. By combining data obtained by karyotyping, array
      CGH, FISH, and multiplex ligation-mediated probe amplification (MLPA) we
      identified a 5 Mb deletion of the 1q44 --> qter region resulting from a paternal
      t(1;20)(q44;q13.33). This smallest 1q44 deletion reported so far, enabled us to
      significantly narrow down the number of candidate genes for the DWC in this
      region. Since the ZNF124 transcription factor is strongly expressed in the fetal
      brain it may represent a candidate gene for the DWC at 1q44.

PMID- 17431902
TI  - Identification of three novel TECTA mutations in Iranian families with autosomal
      recessive nonsyndromic hearing impairment at the DFNB21 locus.
AB  - Forty-five consanguineous Iranian families segregating autosomal recessive
      nonsyndromic hearing loss (ARNSHL) and negative for mutations at the DFNB1 locus
      were screened for allele segregation consistent with homozygosity by descent
      (HBD) at the DFNB21 locus. In three families demonstrating HBD at this locus,
      mutation screening of TECTA led to the identification of three novel homozygous
      mutations: one frameshift mutation (266delT), a transversion of a cytosine to an
      adenine (5,211C > A) leading to a stop codon, and a 9.6 kb deletion removing exon
      10. In total, six mutations in TECTA have now been described in families
      segregating ARNSHL. All of these mutations are inactivating and produce a similar
      phenotype that is characterized by moderate-to-severe hearing loss across
      frequencies with a mid frequency dip. The truncating nature of these mutations is
      consistent with loss-of-function, and therefore the existing TECTA knockout mouse
      mutant represents a good model in which to study DFNB21-related deafness.

PMID- 17431904
TI  - An 11q terminal deletion and tetralogy of Fallot.

PMID- 17431903
TI  - Differential effects of trisomy on brain shape and volume in related aneuploid
      mouse models.
AB  - Down syndrome (DS) results from inheritance of three copies of human chromosome
      21 (Hsa21). Individuals with DS have a significantly smaller brain size overall
      and a disproportionately small cerebellum. The small cerebellum is seen in Ts65Dn
      mice, which have segmental trisomy for orthologs of about half the genes on Hsa21
      and provide a genetic model for DS. While small cerebellar size is well
      established in mouse and humans, much less is known about the shape of the brain
      in trisomy. Here we conduct a morphometric analysis of the whole brain and
      cerebellum in Ts65Dn mice and show that the differences with euploid littermates
      are largely a function of volume and not of shape. This is not the case in two
      aneuploid mouse models that have fewer genes orthologous to Hsa21 than Ts65Dn.
      Ts1Rhr is trisomic for genes corresponding to the so-called Down syndrome
      critical region (DSCR), which was purported to contain a dosage sensitive gene or
      genes responsible for many phenotypes of DS. Ms1Rhr is monosomic for the same
      segment. These models show effects on cerebellum and overall brain that are
      different from each other and from Ts65Dn. These models can help to identify the
      contributions of genes from different regions of the chromosome on this and other
      aspects of brain development in trisomy.

PMID- 17431905
TI  - Mandibulofacial dysostosis in a patient with a de novo 2;17 translocation that
      disrupts the HOXD gene cluster.
AB  - Treacher Collins syndrome (TCS) is the prototypical mandibulofacial dysostosis
      syndrome, but other mandibulofacial dysostosis syndromes have been described. We
      report an infant with mandibulofacial dysostosis and an apparently balanced de
      novo 2;17 translocation. She presented with severe lower eyelid colobomas
      requiring skin grafting, malar and mandibular hypoplasia, bilateral microtia with
      external auditory canal atreasia, dysplastic ossicles, hearing loss, bilateral
      choanal stenosis, cleft palate without cleft lip, several oral frenula of the
      upper lip/gum, and micrognathia requiring tracheostomy. Her limbs were normal.
      Chromosome analysis at the 600-band level showed a 46,XX,t(2;17)(q24.3;q23)
      karyotype. Sequencing of the entire TCOF1 coding region did not show evidence of
      a sequence variation. High-resolution genomic microarray analysis did not
      identify a cryptic imbalance. FISH mapping refined the breakpoints to 2q31.1 and
      17q24.3-25.1 and showed the 2q31.1 breakpoint likely affects the HOXD gene
      cluster. Several atypical findings and lack of an identifiable TCOF1 mutation
      suggest that this child has a provisionally unique mandibulofacial dysostosis
      syndrome. The apparently balanced de novo translocation provides candidate loci
      for atypical and TCOF1 mutation negative cases of TCS. Based on the agreement of
      our findings with one previous case of mandibulofacial dysostosis with a 2q31.1
      transocation, we hypothesize that misexpression of genes in the HOXD gene cluster
      produced the described phenotype in this patient.

PMID- 17431906
TI  - Novel syndrome of cataracts, retinitis pigmentosa, late onset deafness and sperm
      abnormalities: a new Usher syndrome subtype with X-linked inheritance?
AB  - Tissues of the auditory, ocular and reproductive systems have some similarities
      in their protein families and structures. Consequently, syndromes comprising
      these systems are described. Hearing loss alone is a component of more than 400
      known syndromes and is a common nonsyndromic congenital disorder. Here we
      describe a syndrome in five brothers with the distinctive presentation of late
      onset progressive hearing loss, cataracts, retinitis pigmentosa, sperm motility
      and shape problems in a family from the Kurdish population in Iran. The clinical
      findings of these patients are presented in detail and compared to the classical
      Usher syndromes.

PMID- 17431907
TI  - Prenatal diagnosis of partial trisomy 1q and monosomy X in a fetus with a
      congenital lung lesion and hydrops fetalis.
AB  - We report on the prenatal diagnosis of partial trisomy 1q and monosomy X in a
      fetus with a congenital lung lesion and hydrops. The finding of hydrops in a
      fetus with a small lung lesion, congenital cystic adenomatoid malformation (CCAM)
      volume to head circumference ratio (CVR) 0.78, prompted cytogenetic analysis of
      amniotic fluid, revealing an unbalanced translocation between chromosomes X and 1
      [46,X,der(X)t(X;1)(p11.2;q25 or q31)]. The incidence of chromosomal abnormalities
      with CCAM lesions is estimated at 1.6%. This is the first reported case of
      prenatally diagnosed partial trisomy 1q and monosomy X presenting as a fetal lung
      lesion and hydrops.

PMID- 17431908
TI  - Otopalatodigital syndrome type 2 in two siblings with a novel filamin A 629G>T
      mutation: clinical, pathological, and molecular findings.
AB  - Otopalatodigital syndrome type 2 (OPD2) is an uncommon X-linked condition
      characterized by dysmorphic facies, a skeletal dysplasia affecting the axial and
      appendicular skeleton and extraskeletal anomalies including malformations of the
      brain, heart, genitourinary system, and intestines. Missense mutations of the
      FLNA gene, which encodes for the protein filamin A, have recently been shown to
      cause OPD2 and the allelic syndromes otopalatodigital type 1, Melnick-Needles,
      and frontometaphyseal dysplasia. Collectively these conditions constitute the
      otopalatodigital spectrum disorders. We report on two sibs affected by OPD2. The
      diagnosis was achieved at autopsy of a macerated male stillborn with typical
      external and skeletal findings of OPD2. A subsequent pregnancy was terminated due
      to ultrasonographic findings resembling those observed in the previous sibling.
      Histopathological studies revealed osseus sclerosis and do not support the
      previously reported membranous ossification defect observed in this condition.
      Mutation analysis demonstrated a novel mutation, 629G>T, in FLNA that had arisen
      de novo in the mother. This missense mutation predicts the substitution C210F
      within the second calponin homology domain of the actin-binding domain of filamin
      A. The identical substitution has been recently identified in an analogous amino
      acid position within the actin binding domain of beta-spectrin leading to
      hereditary spherocytosis. The observation that phenylalanine is normally present
      in the same position in other proteins (utrophin, dystrophin) but leads to
      disease when present in filamin A implies that the function and/or structure of
      these actin binding domains are not entirely equivalent.

PMID- 17431909
TI  - Laminectomies and achondroplasia: does body mass index influence surgical
      outcomes?
AB  - Obesity is a widespread and potentially serious health problem in individuals
      with achondroplasia. In addition to obesity, such individuals commonly experience
      lumbar spinal stenosis. Although laminectomies have long been the method of
      choice for thorough lumbar decompression, to the best of our knowledge, the
      relationship between body mass index (BMI) and surgical outcomes after
      laminectomy in patients with achondroplasia has not been investigated in a large
      patient population. Through a retrospective medical record review of the initial
      laminectomies of all individuals with achondroplasia at our institution for whom
      adequate records were available, we evaluated the influence of BMI on surgical
      outcomes after laminectomy via four criteria: (1) change in Rankin score; (2)
      change in walking distance; (3) intra-operative and post-operative complications;
      and (4) need for subsequent revision laminectomies. The 49 individuals (mean BMI:
      31.5 kg/m(2) at the time of laminectomy) were stratified into the standard BMI
      categories: normal (<25 kg/m(2)), overweight (25-29.9 kg/m(2)), obese Class I (30
      34.9 kg/m(2)), and a combined obese Class II (35-39.9 kg/m(2)) and obese Class
      III (>40 kg/m(2)). Our analysis indicated that there was no statistical
      difference between these groups in terms of the four criteria. When the study
      group was categorized into non-obese (normal weight and overweight) and obese
      (obese Classes I and II/III) groups, there was also no statistically significant
      improvement difference in terms the same four criteria. Our data suggest that
      obesity does not pose additional risks to laminectomy in individuals with
      achondroplasia.

PMID- 17431910
TI  - Familial multiple pterygium syndrome (MPS) is not associated with CHRNG gene
      mutation.

PMID- 17431911
TI  - Contiguous deletion of the NDP, MAOA, MAOB, and EFHC2 genes in a patient with
      Norrie disease, severe psychomotor retardation and myoclonic epilepsy.
AB  - Norrie disease (ND) is an X-linked disorder, inherited as a recessive trait that,
      therefore, mostly affects males. The gene responsible for ND, called NDP, maps to
      the short arm of chromosome X (Xp11.4-p11.3). We report here an atypical case of
      ND, consisting of a patient harboring a large submicroscopic deletion affecting
      not only the NDP gene but also the MAOA, MAOB, and EFHC2 genes. Microarray
      comparative genomic hybridization (CGH) analysis showed that 11 consecutive
      bacterial artificial chromosome (BAC) clones, mapping around the NDP gene, were
      deleted. These clones span a region of about 1 Mb on Xp11.3. The deletion was
      ascertained by fluorescent in situ hybridization (FISH) analysis with different
      BAC clones located within the region. Clinical features of the proband include
      bilateral retinal detachment, microcephaly, severe psychomotor retardation
      without verbal language skills acquired, and epilepsy. The identification and
      molecular characterization of this case reinforces the idea of a new contiguous
      gene syndrome that would explain the complex phenotype shared by atypical ND
      patients.

PMID- 17431912
TI  - De novo trisomy 20p of paternal origin.
AB  - We report on a case of a de novo trisomy 20p in a 5-year-old boy. The patient
      presented with dysmorphic features, mental retardation, poor coordination,
      cardiac malformation, kyphosis, hypospadias, cryptorchidism, and preaxial
      hexadactyly. No growth delay was noticed. Standard karyotype and FISH techniques
      allowed the characterization of the chromosome rearrangement showing a
      duplication spanning almost the whole short arm of chromosome 20. Therefore the
      karyotype was interpreted as 46,XY,der(20)(pter --> q13.3::p11.2 --> pter).
      Molecular studies identified the duplication of paternal origin. This is one of
      the rare reports with almost pure trisomy 20p characterized at the molecular
      level. Its phenotype is compared to other similar cases described in the
      literature.

PMID- 17431913
TI  - Late-onset cobalamin-C disorder: a challenging diagnosis.
AB  - Cobalamin-C (cblC) disease is a rare autosomal recessive disorder due to
      defective intracellular cobalamin metabolism. There are few (13) reported
      patients of the late-onset presentation of cblC disease with paucity of detailed
      clinical descriptions. This results in this condition being easily missed. In
      this report, we describe clinical and biochemical findings of two unrelated
      patients with late-onset cblC disease who presented with neuropsychiatric
      symptoms. Serial MRI images are provided for one of these patients. Presumptive
      diagnosis was made with urine and plasma biochemical markers and confirmed with
      fibroblast analysis. These patients illustrate the challenging diagnosis of this
      disease and also report on the rare associated findings of vasculopathy and
      mitochondrial respiratory chain dysfunction. Mutation analysis of the MMACHC gene
      showed that both patients were homozygous for 394C --> T which suggests a founder
      effect.

PMID- 17431914
TI  - Mosaicism del(22)(q11.2q11.2)/dup(22)(q11.2q11.2) in a patient with features of
      22q11.2 deletion syndrome.
AB  - The chromosome 22q11 region is prone to rearrangements, including deletions and
      duplications, due to the presence of multiple low copy repeats (LCRs).
      DiGeorge/velo-cardio-facial syndrome is the most common microdeletion syndrome
      with more than 90% of patients having a common 3-Mb deletion of 22q11.2 secondary
      to non-homologous recombination of flanking LCRs. Meiotic reciprocal events
      caused by LCR-mediated rearrangement should theoretically lead to an equal number
      of deletions and duplications. Duplications of this region, however, have been
      infrequently reported and vary in size from 3 to 6 Mb. This discrepancy may be
      explained by the difficulty in detecting the duplication and the variable,
      sometimes quite mild phenotype. This newly described 22q duplication syndrome is
      characterized by palatal defects, cognitive deficits, minor ear anomalies, and
      characteristic facial features. We report on a male with truncus arteriosus and
      an interrupted aortic arch, immunodeficiency, and hypocalcemia. The patient is
      mosaic for two abnormal cell lines: a deletion [del(22)(q11.2q11.2)] found in 11
      cells and a duplication [dup(22)(q11.2q11.2)] found in 9 cells. Molecular
      cytogenetic analysis in our patient revealed a 1.5 Mb deletion/duplication, the
      first duplication reported of this size. Deletion/duplication mosaicism, which is
      rare, has been reported in a number of cases involving many different chromosome
      segments. We present the clinical phenotype of our patient in comparison to the
      phenotypes seen in patients with the 22q11.2 deletion or duplication alone. We
      propose that this rearrangement arose by a mitotic event involving unequal
      crossover in an early mitotic division facilitated by LCRs.

PMID- 17431915
TI  - Wide phenotypic variations within a family with SALL1 mutations: Isolated
      external ear abnormalities to Goldenhar syndrome.
AB  - We report on wide phenotypic variations within a family with SALL1 mutations; the
      elder sister presented with a Townes-Brocks syndrome phenotype including external
      ear anomalies, preaxial polydactyly, and anteriorly placed anus, whereas the
      younger sister presented with a phenotype resembling Goldenhar syndrome,
      including atretic ear canals, mandibular hypoplasia, and right preaxial
      polydactyly as well as an epibulbar dermoid. The mother had abnormal external
      ears but was otherwise structurally normal, and the father was asymptomatic.
      Analysis of the SALL1 gene revealed that both daughters were heterozygous for
      nonsense mutation 1256T>A (L419X), that is present 5' to the region encoding the
      first double zinc finger. The mother was heterozygous for the L419X mutation. The
      younger daughter is the first patient with a SALL1 mutation to exhibit a classic
      Goldenhar syndrome-like phenotype with an epibulbar dermoid. The observation
      lends further support to the concept that Goldenhar syndrome is an etiologically
      heterogeneous disorder that may have a genetic basis in some cases.

PMID- 17431916
TI  - Small supernumerary marker chromosome causing partial trisomy 6p in a child with
      craniosynostosis.
AB  - We report on a child with a small supernumerary marker chromosome (sSMC) causing
      partial trisomy 6p. The child showed a phenotype consisting of neonatal
      craniosynostosis, microcephaly, and borderline developmental delay. By molecular
      techniques the sSMC has been shown to contain approximately 16 Mb of genomic DNA
      from 6p21.1 to 6cen, being de novo and of maternal origin.

PMID- 17431917
TI  - How exhaustive are reviews in research review articles?

PMID- 17431918
TI  - Al-Awadi/Raas-Rothschild syndrome: two new cases and review.
AB  - Al-Awadi/Raas-Rothschild syndrome, an autosomal recessive disorder, is
      characterized by severe malformations of the upper and lower limbs, and a
      hypoplastic pelvis. We describe two new cases with the typical manifestations,
      report some new findings, review the relevant literature, and present minimal
      criteria for the diagnosis. A single homozygous WNT7A mutation was identified by
      Woods et al. [2006]: 1179C --> T, resulting in Arg292Cys with complete loss of
      WNT7A function.

PMID- 17431919
TI  - Compound heterozygosity for dominant and recessive GJB2 mutations: effect on
      phenotype and review of the literature.
AB  - Mutations in GJB2 (which encodes the gap-junction protein connexin 26) are the
      most common cause of genetic deafness in many populations. To date, more than 100
      deafness-causing mutations have been described in this gene. The majority of
      these mutations are inherited in an autosomal recessive manner, but approximately
      19 GJB2 mutations have been associated with dominantly inherited hearing loss.
      One, W44C, was first identified in two families from France. We subsequently
      described a family in the United States with the same mutation. In these
      families, W44C segregates with a dominantly inherited, early-onset, progressive,
      sensorineural deafness that is worse in the high frequencies. Since that report,
      we have tested additional family members and identified two siblings who are
      compound heterozygous for the W44C and K15T mutations. Their father, the original
      proband, is heterozygous for the dominant W44C mutation, and their mother is
      compound heterozygous for two recessively inherited mutations, K15T and 35delG.
      Both children have a profound, sensorineural deafness and use manual
      communication, in contrast to their parents and other relatives whose hearing
      losses are less severe and who can communicate orally. The difference in
      phenotype may be a result of the disruption of different functions of the gap
      junction protein by the two mutations, which have an additive effect.

PMID- 17431920
TI  - Partial trisomy of distal 19q detected by quantitative real-time PCR and FISH in
      a girl with mild facial dysmorphism, hypotonia and developmental delay.
AB  - We report on a 2 7/12-year-old girl who was referred to us because of psychomotor
      developmental delay. She is the second child of healthy, non-consanguineous
      parents. Pregnancy and birth were uneventful. Milestones of motor development
      were delayed: grasping at 6 months, sitting without support at 16 months,
      crawling at 16 months and walking at 2 4/12 years of age. She spoke about five
      words and followed simple instructions. Banding cytogenetics revealed a
      numerically and structurally normal female karyotype of 46,XX. By quantitative
      real-time PCR analysis of all subtelomeric regions, a partial trisomy of the
      subtelomeric region of 19q could be detected. This result was confirmed by FISH
      analysis with a subtelomeric probe for 19q. The additional material of chromosome
      19q was localized on chromosome 6q. However, a deletion of the subtelomeric
      region of 6q could not be detected with a subtelomeric FISH probe for 6q.
      Conventional cytogenetic analysis as well as FISH with subtelomeric probes for
      19q and 6q showed normal results in the parents. The detected chromosomal
      aberration probably occurred de novo. The clinical features are very likely to be
      caused solely by the partial trisomy 19q.

PMID- 17431921
TI  - Genetic counseling utilization by families with offspring affected by birth
      defects, Hawaii, 1986-2003.
AB  - Information on the genetic counseling facility utilization by families with
      offspring affected by birth defects in the United States is limited. The intent
      of this study was to report on genetic counseling utilization in Hawaii. Cases
      were all infants and fetuses of any pregnancy outcome with major birth defects
      included in a Hawaii birth defects registry and delivered during 1986-2003. The
      genetic counseling facility utilization rates were determined for various factors
      and evaluated for significance by calculating the rate ratio (RR) and 95%
      confidence interval (CI). Of 15,104 total cases, genetic counseling facilities
      were utilized in 1,596 (10.6%). Utilization rates were higher with the presence
      of multiple major birth defects (RR 3.06, 95% CI 2.75-3.42), chromosomal
      abnormalities (RR 4.25, 95% CI 3.82-4.73), and malformation syndromes (RR 6.83,
      95% CI 5.85-7.93). Among 54 specific birth defects, the utilization rate varied
      from 1.5% for pyloric stenosis to 55.3% for holoprosencephaly and was
      significantly higher for 31 (57.4%) of the defects. Greater utilization rates
      were found with live births that had expired within 1 year after delivery (RR
      2.86, 95% CI 2.42-3.36), fetal deaths (RR 1.59, 95% CI 1.23-2.03), elective
      terminations (RR 5.76, 95% CI 5.06-6.55), and maternal age > or =35 years (RR
      1.59, 95% CI 1.41-1.78). Genetic counseling facility utilization rates were much
      higher with the presence of multiple major birth defects, chromosomal
      abnormalities, and malformation syndromes, certain specific birth defects, death
      of the fetus or infant, and older maternal age.

PMID- 17431922
TI  - EEC syndrome, Arg227Gln TP63 mutation and micturition difficulties: Is there a
      genotype-phenotype correlation?
AB  - We report on two unrelated families with EEC syndrome (ectrodactyly, ectodermal
      dysplasia, cleft lip/palate), each with an Arg227Gln TP63 gene mutation, where
      the phenotype overlapped extensively with the allelic disorder, limb-mammary
      syndrome (LMS). Features common to both families were an ectodermal dysplasia
      principally affecting tooth, breast and nipple development, dacryostenosis and
      severe micturition difficulties. Additional findings included post-axial digital
      hypoplasia, cleft uvula, anal stenosis, hypoplasia of the perineal body and
      biopsy-proven interstitial cystitis. No individual had cleft lip. Split hand
      split foot malformation (SHFM) occurred in one child-born after the molecular
      diagnosis was established. Unlike previous reports, the urinary symptoms were
      refractory to treatment with oral Fibrase and persisted into adulthood. Of the
      six cases/families now reported with EEC syndrome and Arg227Gln TP63 mutation,
      four have manifested this distinct urological abnormality, indicative of a
      genotype-phenotype correlation.

PMID- 17431923
TI  - MTHFR and RFC-1 gene polymorphisms and the risk of Down syndrome in Italy.

PMID- 17431924
TI  - Baculovirus-mediated gene transfer is attenuated by sodium bicarbonate.
AB  - BACKGROUND: Baculovirus transduction of cultured mammalian cells is typically
      performed by incubating the cells with virus using culture medium (e.g.
      Dulbecco's modified Eagle's medium (DMEM)) as the surrounding solution. However,
      we previously uncovered that DMEM hinders the baculovirus-mediated gene transfer.
      METHODS: In this study, we systematically explored the influences of promoter and
      medium constituents on the transduction efficiency by using different recombinant
      viruses and surrounding solutions for transduction, followed by flow cytometric
      analyses. Whether the key medium component impeded baculovirus binding to the
      cells and subsequent virus entry was investigated by immunofluorescence/confocal
      microscopy and quantitative real-time polymerase chain reaction (Q-PCR). RESULTS:
      We demonstrated that the poorer transduction by using DMEM as the surrounding
      solution is independent of the promoter. Examination of the medium constituents
      group by group revealed that the balanced salt solution suppresses the
      baculovirus transduction. By omitting individual salt species in the balanced
      salt solution, we surprisingly uncovered that NaHCO(3), a common buffering agent,
      exerts the inhibitory effects in a concentration-dependent manner. Intriguingly,
      NaHCO(3) did not debilitate the baculovirus, nor did it inhibit virus binding to
      the cells. Instead, NaHCO(3) inhibited baculovirus transduction by reducing the
      intracellular virus number. CONCLUSIONS: To our best knowledge, this is the first
      report unraveling the significance of NaHCO(3) in gene transfer. Our finding
      suggests that baculovirus-mediated gene transfer can be readily enhanced by
      omitting NaHCO(3) from the medium during the transduction period.

PMID- 17431925
TI  - Functional analysis of Candida albicans genes whose Saccharomyces cerevisiae
      homologues are involved in endocytosis.
AB  - PCR-based techniques for directed gene alterations have become standard tools in
      Candida albicans. To help to increase the speed of functional analysis of Candida
      albicans genes, we previously constructed and updated a modular set of pFA
      plasmid vectors for PCR-based gene targeting in C. albicans. Here we report the
      functional analyses of C. albicans ORFs whose homologues in S. cerevisiae are
      involved in endocytosis, to explore their potential involvement in polarized cell
      growth. Three C. albicans genes, ABP1, BZZ1 and EDE1, were found to be non
      essential. Yeast and hyphal morphogenesis were not affected by the individual
      deletions and the mutant strains appeared wild-type-like under the different
      growth conditions tested. On the other hand, deletion of both alleles of the C.
      albicans PAN1 homologue was not feasible. Promoter shut-down experiments using a
      MET3p-PAN1/pan1 strain indicated severe growth defects and abolished endocytosis,
      indicating that PAN1 is an essential gene. Subcellular distribution of CaAbp1 and
      CaPan1 was analysed via GFP-tagged proteins. Both proteins were found to localize
      at the cortex and at hyphal tips in a patch-like manner, supporting their role in
      endocytosis. Localization patterns of Abp1 and Pan1, however, were distinct from
      that of the FM4-64 stained Spitzenkorper.

PMID- 17431926
TI  - Tools and methods for genetic analysis of Saccharomyces castellii.
AB  - The budding yeast species Saccharomyces castellii has provided important new
      insights into molecular evolution when incorporated in comparative genomics
      studies and studies of mitochondrial inheritage. Although it shows some diversity
      in the specific molecular details, several analyses have shown that it contains
      many genetic pathways similar to those of S. cerevisiae. Here we have
      investigated the possibility of performing genetic analyses in S. castellii. We
      optimized the LiAc transformation protocol to achieve 200-300
      transformants/microg plasmid DNA. We found that the commonly used plasmids for S.
      cerevisiae are stably maintained in S. castellii under selective conditions.
      Surprisingly, both 2micro and CEN/ARS plasmids are kept at a high copy number.
      Moreover, the kanMX cassette can be used as a resistance marker against the
      selective drug geneticin (G418). Finally, we determined that the S. cerevisiae
      GAL1 promoter can be used for the activation of transcription in S. castellii,
      thus enabling the controlled overexpression of genes when galactose is present in
      the medium. The availability of these tools provides the possibility of
      performing genetic analyses in S. castellii, and makes it a promising new model
      system in which hypotheses derived from bioinformatics studies can be
      experimentally tested.

PMID- 17431927
TI  - Metabolic differences between Asian and Caucasian patients on clozapine
      treatment.
AB  - OBJECTIVE: To establish if there are ethnic differences in the various metabolic
      disturbances that are common with clozapine treatment. METHOD: Forty subjects (20
      Asians and 20 Caucasians) with a diagnosis of schizophrenia were recruited for
      the study. Clozapine blood levels as well as fasting blood glucose, lipid levels,
      and liver function tests were established. Other clinical parameters such as
      blood pressure and Body Mass Index (BMI) were recorded for each patient. RESULTS:
      The mean clozapine dose was significantly higher in the Caucasian subjects
      (432.5+/-194.7 mg) as compared to the Asian subjects (175.6+/-106.9 mg) (p<0.001)
      while the mean weight-corrected dose for Asian patients was lower (3.0+/-1.9 and
      5.0+/-2.1 mg/kg, respectively, p=0.005). There were, however, no ethnic
      differences in the mean plasma clozapine concentration (415.3+/-185.8 ng/ml in
      Caucasians and 417.1+/-290.8 ng/ml in Asians). BMI were significantly higher in
      Caucasians, as were the number of subjects with hypertension; levels of hepatic
      enzymes were higher in the Asian group. CONCLUSIONS: Not only are there
      pharmacokinetic differences between Asian and Caucasian patients receiving
      clozapine, but there may also be differential emergence of certain metabolic
      abnormalities like hypertension and weight gain in these two ethnic groups.
      However, the effects of life style including diet and exercise cannot be
      excluded.

PMID- 17431928
TI  - Neurocognition of centenarians: neuropsychological study of elite centenarians.
AB  - OBJECTIVE: The aim of this study was to evaluate the cognitive state of highly
      selected Polish centenarians and analyze the mechanisms of their functioning.
      METHODS: The selected centenarian group (10 persons) and a reference group (20
      persons) who started aging (65 years) were examined with a sensitive set of
      neuropsychological tests and tasks in clinical-experimental assessment. RESULTS:
      As expected, the centenarians' cognitive functions were different from those of
      the subjects who started aging, however, not in all aspects. For instance, the
      former scored significantly lower in the area of linguistic functions but the
      ability to plan and controlled perform complex visuospatial task with use of
      simultaneous and sequential strategies was preserved despite unfavorable symptoms
      of natural aging such as permanence attention as well as prolonged action time.
      CONCLUSIONS: The results suggest that the studied centenarians show a dominant
      right-hemispheric pattern functioning not only in relation to perception, but
      also to planning and executing complex activities. The study and description of
      preserved neurocognition of centenarians was possible due to introducing a
      special procedure sensitive to the preserved functions.

PMID- 17431929
TI  - Validation of the Telephone Interview for Cognitive Status (TICS) in Japanese.
AB  - BACKGROUND: In recent years, the population of elderly people in Japan with
      dementia has increased. Detection of cognitive impairment in the early stages is
      important for adequate treatment, care, and prevention. AIM: To investigate
      whether the reliability and validity of the instrument would carry over to a
      different population and language before using it for population-based
      epidemiological studies. METHODS: We studied 135 subjects, 49 patients with
      Alzheimer's disease (AD) and 86 healthy controls (CTL) using the Telephone
      Interview for Cognitive Status (TICS) and developed the Japanese version of the
      TICS (TICS-J). We also evaluated combination of another telephone battery, the
      Category Fluency Test (CF). RESULTS: The sensitivity and specificity of the TICS
      J to differentiate AD patients from CTL was 98.0% and 90.7%, respectively.
      Pearson's correlation coefficient for the TICS-J and Mini-Mental State
      Examination (MMSE) was 0.858 (p < 0.001). On the Receiver Operating
      Characteristic (ROC), the area under the curve for the TICS-J was 98.7%. The
      combination of the TICS-J with the CF did not change the validity of the
      discrimination. CONCLUSION: These results indicated that TICS-J was a sensitive
      and specific instrument for differentiating AD patients from healthy controls.

PMID- 17431930
TI  - Reference charts and equations of Korean fetal biometry.
AB  - OBJECTIVE: To construct new reference charts and equations for fetal biparietal
      diameter (BPD), head circumference (HC), abdominal circumference (AC) and femur
      diaphysis length (FDL) from Korean fetuses at 12-40 weeks. METHOD: Prospective
      cross-sectional data obtained in one center for 5 years from a population of
      pregnant women undergoing ultrasound examination between the 12th and 40th week
      of gestation. Exclusion criteria comprised all maternal and fetal conditions
      possibly affecting fetal biometry. No fetuses were excluded on the basis of
      abnormal biometry. For each measurement, regression models were fitted to
      estimate both the mean and the standard deviation at each menstrual age. RESULTS:
      Biometric measurements were obtained for 10 455 fetuses. New charts and reference
      equations are reported for BPD, HC, AC and FDL. Reference equations are cubic
      models. CONCLUSION: We present new Korean reference charts and equations for
      fetal biometry. They can be easily used in obstetric ultrasound studies for the
      Korean population.

PMID- 17431931
TI  - Side-on versus end-on bonding of O2 to the FSO3 radical: matrix isolation and ab
      initio study of FSO5.

PMID- 17431932
TI  - A versatile method for direct and covalent immobilization of DNA and proteins on
      biochips.

PMID- 17431933
TI  - Human exhaled air analytics: biomarkers of diseases.
AB  - Over the last few years, breath analysis for the routine monitoring of metabolic
      disorders has attracted a considerable amount of scientific interest, especially
      since breath sampling is a non-invasive technique, totally painless and agreeable
      to patients. The investigation of human breath samples with various analytical
      methods has shown a correlation between the concentration patterns of volatile
      organic compounds (VOCs) and the occurrence of certain diseases. It has been
      demonstrated that modern analytical instruments allow the determination of many
      compounds found in human breath both in normal and anomalous concentrations. The
      composition of exhaled breath in patients with, for example, lung cancer,
      inflammatory lung disease, hepatic or renal dysfunction and diabetes contains
      valuable information. Furthermore, the detection and quantification of oxidative
      stress, and its monitoring during surgery based on composition of exhaled breath,
      have made considerable progress. This paper gives an overview of the analytical
      techniques used for sample collection, preconcentration and analysis of human
      breath composition. The diagnostic potential of different disease-marking
      substances in human breath for a selection of diseases and the clinical
      applications of breath analysis are discussed.

PMID- 17431934
TI  - Simultaneous determination and pharmacokinetic study of oxymatrine and matrine in
      beagle dog plasma after oral administration of Kushen formula granule, oxymatrine
      and matrine by LC-MS/MS.
AB  - A rapid, specific and sensitive LC-MS/MS method was developed for the
      determination of oxymatrine (OMT) and matrine (MT) in beagle dog plasma. The
      method was applied to study the pharmacokinetics of OMT and MT after oral
      administration of OMT, MT and Kushen formula granule (KFG) containing equivalent
      amounts of OMT and MT in a three-period crossover design. The analysis was
      carried out on an Acquity UPLC BEH C(18) column by linear gradient elution with
      0.01% acetic acid-water-methanol as mobile phase. Detection was by positive ion
      electrospray ionization (ESI) mass spectrometry with multiple-reaction monitoring
      (MRM). Linear calibration curves were both obtained over the concentration range
      15-2000 ng/mL, with a limit of quantification of 15 ng/mL. The matrix effect was
      minimized. The intra- and inter-day precisions (RSDs) were less than 12.4 and
      14.7%, respectively, and the accuracy (RE) was from -2.1 to 2.7%. The validated
      method was used to determine the concentration-time profiles of OMT and MT. The
      results indicated that the absorption of OMT and MT after oral administration of
      KFG was significantly greater than that after oral administration of pure
      components.

PMID- 17431935
TI  - Fingerprint analysis of Rhizoma chuanxiong by pressurized capillary
      electrochromatography and high-performance liquid chromatography.
AB  - Pressurized capillary electrochromatography (pCEC) and high-performance liquid
      chromatography (HPLC) were used simultaneously to establish fingerprints of
      Rhizoma chuanxiong. Ten batches of Rhizoma chuanxiong collected from different
      regions in China were used to obtain the characteristic pCEC and HPLC
      fingerprints using a standardized procedure of sample preparation and analysis. A
      total of 22 common peaks were isolated within 60 min by pCEC and 16 common peaks
      by HPLC within 65 min. The fingerprints of Rhizoma chuanxiong were then used to
      identify the raw herbs from different sources in China. The two proposed methods
      demonstrated good stability and reproducibility with RSD less than 5% for
      retention time in pCEC and in HPLC, respectively. Finally, the data from the
      analyses of 10 batches of Rhizoma chuanxiong by pCEC and HPLC were all processed
      with similarity analysis with two mathematical methods, correlation coefficient
      and the included angle cosine. The fingerprints of Rhizoma chuanxiong established
      with pCEC and HPLC are suitable to identify samples from different sources and
      can be used to control the quality of raw herbs.

PMID- 17431936
TI  - Correlated ab initio quantum chemical calculations of di- and trisaccharide
      conformations.
AB  - High level correlated quantum chemical calculations, using MP2 and local MP2
      theory, have been performed for conformations of the disaccharide, beta-maltose,
      and the trisaccharide, 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranose.
      For beta-maltose, MP2 and local MP2 calculations using the 6-311++G** basis set
      are in good agreement, predicting a global minimum gas-phase conformation with a
      counterclockwise hydrogen bond network and the experimentally-observed
      intersaccharide hydrogen bonding arrangement. For conformations of 3,6-di-O
      (alpha-D-mannopyranosyl)-alpha-D-mannopyranose, MP2/6-311++G**, and local MP2/6
      311++G** calculations do not provide a consensus prediction of relative
      energetics, with the MP2 method finding large differences in stability between
      extended and folded trisaccharide conformations. Local MP2 calculations, less
      susceptible to intramolecular basis set superposition errors, predict a narrower
      range of trisaccharide energetics, in line with estimates from Hartree-Fock
      theory and B3LYP and BP86 density functionals. All levels of theory predict
      compact, highly hydrogen-bonded conformations as lowest in energy on the in vacuo
      potential energy surface of the trisaccharide. These high level, correlated local
      MP2/6-311++G** calculations of di- and trisaccharide energetics constitute
      potential reference data in the development and testing of improved empirical and
      semiempirical potentials for modeling of carbohydrates in the condensed phase.

PMID- 17431937
TI  - Performance of the general amber force field in modeling aqueous POPC membrane
      bilayers.
AB  - The aim of this work was to answer the question of whether the general amber
      force field (GAFF) is good enough to simulate fully hydrated POPC membrane
      bilayers. The test system contained 128 POPC and 2985 TIP3P water molecules. The
      equilibration was carried out in a nonarbitrary manner to reach the stable liquid
      crystalline phase. The simulations were performed by using particle mesh Ewald
      electrostatics implemented in molecular dynamics packages Amber8 (NPT ensembles)
      and NAMD2 (NPgammaT ensembles). The computational results were assessed against
      the following experimental membrane properties: (i) area per lipid, (ii) area
      compressibility modulus, (iii) order parameter, (iv) gauche conformations per
      acyl chain, (v) lateral diffusion coefficients, (vi) electron density profile,
      and (vii) bound water at the lipid/water interface. The analyses revealed that
      the tested force field combination approximates the experimental values at an
      unexpectedly good level when the NPgammaT ensemble is applied with a surface
      tension of 60 mN m(-1) per bilayer. It is concluded that the GAFF/TIP3P
      combination can be utilized for aqueous membrane bilayer simulations, as it
      provides acceptable accuracy for biomolecular modeling.

PMID- 17431938
TI  - Description of Cameronieta torrei dusbabeki (Acari: Mesostigmata:
      Spinturnicidae), new subspecies with nymphs, parasitizing Pteronotus quadridens
      fuliginosus (Chiroptera: Mormoopidae) from Puerto Rico.
AB  - We describe a new subspecies, Cameronieta torrei dusbabeki, a parasite of
      Pteronotus quadridens fuliginosus (Gray 1843) from Puerto Rico.

PMID- 17431939
TI  - Publication outcome for research presented at the  Vascular Society of Great
      Britain and Ireland  annual meetings.
AB  - BACKGROUND The Vascular Society of Great Britain and Ireland (VSGBI) annual
      meeting is a major international vascular surgery conference. Studies suggest
      that the percentage of presentations that result in full-text publications are a
      measure of the quality of the meeting. We investigated the publication outcome of
      abstracts presented to the VSGBI in 2001 and 2002. MATERIALS AND METHODS We
      retrospectively identified abstracts from the conference programmes and conducted
      a detailed electronic Medline and PubMed search to determine publication. We
      collected data regarding the study design, subject matter,publishing journal,
      time to publication, institution of origin, impact factors and RAE levels.
      RESULTS There were 63 publications from 106 abstracts (59.4%), with a median
      impact factor of 3.507. Prospective observational studies accounted for 20.6% of
      publications, with abdominal aortic aneurysms being the commonest subject
      matter(34.9%). The median time to publication was 12 months, with the European
      Journal of Vascular and Endovascular Surgery publishing 33.3% of the articles.
      Leicester achieved the highest number of publications and the majority of work
      came from centres with Research Assessment Exercise (RAE) level scores of 4,
      university centres accounted for 74.6% of publications. CONCLUSIONS We conclude
      that when compared to equivalent meetings in other specialties and geographical
      regions, the annual meeting of the VSGBI is of the very highest quality.

PMID- 17431940
TI  - Congenital hyperinsulinism and related disorders, June 15-16, 2006, Philadelphia,
      PA, USA.

PMID- 17431941
TI  - A new curriculum for surgical training within the United Kingdom: context and
      model.

PMID- 17431942
TI  - A new curriculum for surgical training within the United kingdom: the first
      stages of implementation.

PMID- 17431943
TI  - [First experiences with the CoreValve heart valve prosthesis. Percutaneous
      retrograde implantation os a self-expanding aortic valve prosthesis for the
      treatment of patients at risk with symptomatic aortic valve stenosis].

PMID- 17431944
TI  - [The Nordic Bifurcation Study. Randomized study on the question of optimal
      stenting technique for bifurcating stenosis].

PMID- 17431945
TI  - [CAPTURE 2500. Carotid RX ACCULINK/RX ACCUNET post-admission study (registry) of
      carotid stent implantation].

PMID- 17431946
TI  - [The BASKET-LATE-Study. Basel stent cost-effectiveness trial--late thrombotic
      events trial].

PMID- 17431947
TI  - [Heart insufficiency--what is it?].

PMID- 17431948
TI  - California awards US$45 million for stem-cell research.

PMID- 17431949
TI  - Is it all over for erythropoietin?

PMID- 17431950
TI  - Dasatinib is effective in imatinib-resistant CML.

PMID- 17431951
TI  - Pertuzumab brake for prostate cancer?

PMID- 17431952
TI  - New predictors of survival for early-stage NSCLC.

PMID- 17431953
TI  - Rectal-cancer radiation and prostate-cancer risk.

PMID- 17431954
TI  - Satraplatin for hormone-refractory prostate cancer.

PMID- 17431955
TI  - Carcinogenicity of alcoholic beverages.

PMID- 17431956
TI  - Afferent loop syndrome secondary to Billroth II gastrojejunostomy obstruction:
      Multidetector computed tomography findings.

PMID- 17431958
TI  - Lower extremity injuries among high school cross-country runners.

PMID- 17431959
TI  - A home-based exercise program for women with HIV.

PMID- 17431957
TI  - International integrated database for the evaluation of severe sepsis and
      drotrecogin alfa (activated) therapy: analysis of efficacy and safety data in a
      large surgical cohort.
AB  - BACKGROUND: The International Integrated Database for the Evaluation of Severe
      Sepsis and Drotrecogin alfa (activated) Therapy includes an extensive cohort of
      surgical patients (1659/4459; 37%). This database broadens the experience
      reported on a comparatively small set of surgical patients from the pivotal
      Protein C Worldwide Evaluation in Severe Sepsis trial to examine issues of safety
      and efficacy in a much larger cohort. METHODS: We conducted a retrospective
      analysis of prospectively defined outcomes from 5 integrated clinical studies of
      severe sepsis. Multivariable analyses incorporated propensity scores, treatment,
      and significant baseline risk factors as independent variables in logistic
      regression models for 2 outcomes: serious adverse events that were observed
      during infusion and 28-day, all-cause mortality rates. Adjusted odds ratios were
      calculated for clinically important strata. Multiple subcategories of serious
      bleeding-event rates are presented. RESULTS: Although surgical patients who were
      treated with drotrecogin alfa [activated] (DrotAA) experienced a greater
      proportion of serious bleeding events during the infusion period, most of the
      patients were treated without fatal consequence. A 10.7% absolute all cause
      mortality risk reduction (adjusted odds ratio, 0.66; 95% CI, 0.45-0.97) was
      observed for DrotAA-treated, high-risk (Acute Physiology and Chronic Health
      Evaluation II, >/= 25) surgical patients. We could not demonstrate a survival
      benefit in DrotAA-treated, low-risk (Acute Physiology and Chronic Health
      Evaluation II, <25) surgical patients. When surgical patients were stratified by
      number of organ dysfunctions, absolute risk reductions were observed in both
      categories: multiorgan (4.3%) and single (4.5%). CONCLUSION: International
      Integrated Database for the Evaluation of Severe Sepsis and Drotrecogin alfa
      (activated) Therapy analyses affirmed the favorable benefit/risk profile of
      DrotAA for surgical patients. The serious adverse event rate that was experienced
      by surgical patients during the study drug infusion period was 7.5% in the DrotAA
      treated group versus 6.3% in the placebo-treated group (odds ratio, 1.41; 95% CI,
      0.89-2.25). The clinical benefit of DrotAA therapy paralleled baseline risk of
      death and substantiated findings from the Protein C Worldwide Evaluation in
      Severe Sepsis study. Future analyses are needed to evaluate the special
      relationships among sepsis severity, bleeding management, and the postoperative
      timing of DrotAA administration.

PMID- 17431960
TI  - Investment returns and size of damage caps impact rising cost of malpractice
      premiums.

PMID- 17431961
TI  - HIV/AIDS in Africa: a day in the life of a nurse in Malawi.

PMID- 17431962
TI  - [Prevention of cardiovascular diseases--real way to improvement of demographic
      situation in Russia].

PMID- 17431963
TI  - Engaging nursing preceptor-student dyads in an evidence-based approach to
      professional practice.

PMID- 17431964
TI  - [The use of tenecteplase in acute myocardial infarction].

PMID- 17431966
TI  - [Three lives of captopril in the era of evidence based medicine].

PMID- 17431965
TI  - [Pulmonary hypertension and right ventricular failure. Part VI. Classification
      and pathomorphology of primary pulmonary arterial hypertension].
AB  - In a series of articles the authors discuss literature data concerning
      epidemiology of pulmonary hypertension (PH), its modern classification;
      peculiarities of its pathogenesis and treatment in various diseases and
      conditions. In the sixth communication they present classification of PH accepted
      at the Third World PH Symposium (venice, Italy, 2003). This classification
      abandons terms "primary" and "secondary" PH. Primary PH which is now recommended
      to be called "idiopathic pulmonary arterial hypertension" is grouped in one
      category with familial cases of PH, PH associated with administration of
      anorexigens, collagen vascular disease, congenital systemic to pulmonary shunts,
      portal hypertension and hyperthyroidism, as well as with pulmonary veno-occlusive
      disease and and pulmonary capillary hemangiomatosis, taking into consideration
      similarity of histopathological changes of vascular tree, pathophysiology and
      therapeutic approaches in these forms of PH.

PMID- 17431967
TI  - [Effect of bisoprolol and sotalol on clinical status of patients with proximal
      form of atrial fibrillation and chronic heart failure].

PMID- 17431968
TI  - Avoiding jail pays off: diverting people with mental illnesses out of prison
      takes commitment from the community along with adequate funding.

PMID- 17431969
TI  - Delinquency detour: treating mental illness in young people can keep them from a
      future of crime and delinquency.

PMID- 17431971
TI  - [On the 70th anniversary of the death of the founder of brain physiology and
      recipient of the Nobel Prize, I.P. Pavlov (1849-1936)--his thoughts and
      discoveries].

PMID- 17431970
TI  - Helping mentally ill criminals: jailing offenders with mental illnesses serves no
      one, but new policies and funding are bringing about needed changes.

PMID- 17431972
TI  - [Moschowitz or Moschowitzova?].

PMID- 17431973
TI  - [Ivan Petrovic Pavlov (1849-1936)].

PMID- 17431974
TI  - [70 years since the death of a man who belongs among the founders of digestive
      tract physiology].

PMID- 17431975
TI  - When morals and medicine conflict: morning-after pill reignites issues.
AB  - Staff members should have the option of refusing treatment they deem morally or
      ethically objectionable. Plan ahead for such situations, to ensure someone else
      will be available to fill in. Become active in committees that address these
      issues from a hospital-wide perspective.

PMID- 17431976
TI  - Should quality data be collected by race, ethnicity?
AB  - Most quality improvement leaders do not link disparities and QI initiatives and
      do not measure for disparities, according to study. Equity of care is one of the
      six domains of quality identified by the Institute of Medicine. At least one
      state now mandates collection of quality data according to race and ethnicity.

PMID- 17431977
TI  - Two-minute briefing may reduce wrong-site surgeries.
AB  - An effective briefing needn't last longer than about two minutes. The entire care
      team should be involved in the briefing. While certain key elements should always
      be used, hospitals and departments should customize the briefings as much as
      possible and try not to include too many details.

PMID- 17431978
TI  - Demonstration project continues gains in year two.
AB  - Adherence to several measures sees significant improvement from first quarter of
      project to most recent quarter. Payment for performance is only one of the keys
      to success; transparency, knowledge transfer also given much of the credit.
      Quality manager uses reliability science to help meet the challenge of improving
      year after year.

PMID- 17431980
TI  - Subspecialization: commercialism or professionalism?

PMID- 17431979
TI  - 'Full disclosure' approach to errors may be costly.
AB  - Full disclosure may make patients aware of errors they did know had occurred.
      While initial reaction of patients is likely to be gratitude for honesty,
      additional reflection could lead to negative feelings. Study indicates a 95%
      chance that the number of lawsuits would increase under a full disclosure policy.

PMID- 17431981
TI  - Loss of alleles in vestibular schwannomas: use of microsatellite markers on
      chromosome 22.
AB  - OBJECTIVE: Using highly informative microsatellite markers flanking the
      neurofibromatosis type 2 gene, we determined the frequency of chromosome 22
      allele loss in vestibular schwannomas. DESIGN: Peripheral lymphocyte/vestibular
      schwannoma DNA pairs were analyzed with five different microsatellite markers on
      chromosome 22. PATIENTS: Samples were taken from 32 patients (17 females and 15
      males). Twenty-seven tumors occurred sporadically, and five were from patients
      with neurofibromatosis type 2. RESULTS: Using the microsatellite markers D22S351,
      CRYB2, D22S268, D22S304, and interleukin type 2RP3, we found loss of
      heterozygosity for at least two markers in 12 tumors. Ten tumors showed loss of
      heterozygosity for markers flanking the neurofibromatosis type 2 gene. Although
      microsatellite markers require little DNA for analysis and are highly
      informative, allele patterns may be difficult to interpret in some cases.
      CONCLUSIONS: Loss of heterozygosity of chromosome 22 alleles was a frequent event
      in vestibular schwannomas. In 10 tumors, heterozygosity was lost for centromeric
      and telomeric markers indicating likely monosomy 22. However, 63% of tumors did
      not reveal a detectable chromosomal loss. Unless a second vestibular schwannoma
      locus exists, these tumors likely harbor point mutations in the neurofibromatosis
      type 2 gene or deletions below the level of resolution of the markers used in
      this study.

PMID- 17431982
TI  - Immunobiologic effects of cytokine gene transfer of the B16-BL6 melanoma.
AB  - OBJECTIVE: The genetic modification of tumors offers an approach to modulate the
      host immune response to relatively weak native tumor antigens. We examined the
      immunobiologic effects of various cytokine genes transferred into the poorly
      immunogenic B16-BL6 murine melanoma. DESIGN: Retroviral expression vectors
      containing cDNAs for interleukin 2, interleukin 4, interferon gamma, or a
      neomycin-resistant control were electroporated into a B16-BL6 tumor clone.
      Selected transfected clones were examined for in vitro cytokine secretion and in
      vivo tumorigenicity. RESULTS: When cells from individual clones were injected
      intradermally into syngeneic mice, the interleukin 4-secreting clone grew
      significantly slower than did the neomycin-resistant transfected control, while
      the growth of the interleukin 2- and interferon gamma-expressing clones was not
      affected. Despite minimal cytokine secretion by interferon gamma-transfected
      cells, these cells expressed upregulated major histocompatibility class I antigen
      and were more susceptible to lysis by allosensitized cytotoxic T lymphocytes
      compared with parental or neomycin-resistant transfected tumor targets.
      CONCLUSIONS: We observed diverse immunobiologic effects associated with cytokine
      gene transfer into the B16-BL6 melanoma. Interleukin 4 transfection of tumor
      resulted in decreased in vivo tumorigenicity that may be related to a host immune
      response. Further studies to evaluate the host T-cell response to these gene
      modified tumors are being investigated.

PMID- 17431983
TI  - Detection and typing of human papillomavirus in verrucous carcinoma of the oral
      cavity using the polymerase chain reaction.
AB  - OBJECTIVE: This study examined the prevalence and types of human papillomavirus
      (HPV) DNA in oral cavity verrucous carcinoma. DESIGN: This was of a retrospective
      screening study. Formalin-fixed, paraffin-embedded tissue samples were examined
      by the polymerase chain reaction using DNA primers specific for HPV types 6b/11,
      16, and 18. SETTING: The majority of patients were seen at referral centers in
      Ontario, Canada. PATIENTS: This study examined 29 oral cavity verrucous
      carcinomas occurring in a sample of 25 patients from four institutions between
      1966 and 1992. All tumors met standardized histologic diagnostic criteria of
      verrucous carcinoma. MAIN OUTCOME MEASURE: The prevalence of HPV 6b/11, 16, and
      18 DNA was determined by the PCR technique. RESULTS: The HPV DNA was detected in
      12 (48%) of 25 patients. The HPV 6b/11 DNA, HPV 16 DNA, HPV 18 DNA, and HPV 16
      DNA plus HPV 18 DNA, were detected in one (4%), one (4%), nine (36%), and one
      (4%) cases, respectively. CONCLUSIONS: The detection of HPV 18 DNA in 40% of oral
      cavity verrucous carcinomas suggests an association between the presence of HPV
      18 DNA and some oral cavity verrucous carcinomas. The etiologic and prognostic
      significance of HPV 18 for oral cavity verrucous carcinoma remains unanswered and
      will require further study.

PMID- 17431985
TI  - Free tissue transfer for skull base reconstruction analysis of complications and
      a classification scheme for defining skull base defects.
AB  - OBJECTIVE: The role of free flaps in skull base reconstruction is discussed in
      detail. Twenty-six microvascular free tissue transfers performed in 22 patients
      are reviewed in detail. A classification scheme for skull base defects is
      presented. SETTING: Tertiary referral center. PATIENTS: Twenty-two patients with
      neoplasms that involve the skull base underwent a combined craniotomy and facial
      approach for resection. The resultant defects were reconstructed with a variety
      of microvascular free flaps. RESULTS: All 22 patients were ultimately
      successfully reconstructed with a free flap. One patient required a second free
      flap following ablative surgery for a recurrent tumor. The initial free flaps in
      three patients were unsuccessful and a second flap was required. The
      classification scheme was applied to all defects. CONCLUSIONS: The creation of a
      functional separation of the intracranial and extracranial cavities can be
      extremely difficult to accomplish, especially when multiple cavities (nasal,
      oral, pharyngeal) are violated. Free flaps provide a solution to this problem in
      select cases. Skull base defects can and should be classified for the purpose of
      communication, treatment planning, prognosis of reconstruction, and judging
      therapeutic outcome.

PMID- 17431984
TI  - COL1A2 and COL2A1 expression in temporal bone of lethal osteogenesis imperfecta.
AB  - OBJECTIVE: COL1A2 and COL2A1 genes are expressed at high levels in many cochlear
      cells of 16- to 23-week-old human fetuses. Given these prior observations and the
      rare opportunity to obtain temporal bones from a deceased neonate with
      osteogenesis imperfecta (OI) type II, we determined the cellular distribution and
      level of expression of COL1A2 mRNA in OI type II inner ear compared with the
      expression in second-trimester human fetal cochlea. Expression of COL2A1 mRNA was
      assessed for its normal role in OI type II neonatal cochlea and to address
      potential spatial and temporal changes along with our observations in fetal
      cochlea. We describe our tissue in situ hybridization protocol and document its
      usefulness in assessing gene expression in human temporal bone obtained at
      autopsy. DESIGN: RNA-RNA in situ hybridization was performed in formaldehyde
      fixed, decalcified, paraffin-embedded temporal bone sections from a neonate with
      OI type II. Semi-quantitative assessment of gene expression was performed by
      visual inspection of grain densities. RESULTS AND CONCLUSIONS: COL1A2 and COL2A1
      were expressed at moderate-to-high levels in many membranous cochlear cells, and
      no dramatic alterations in pattern or level of expression of these genes was
      noted compared with human fetal cochlea. Consistent with in vitro studies,
      expression of COL1A2 in osteoblasts lining enchondral and endosteal layers is
      less than that in identical cells of the fetal otic capsule undergoing osteoid
      deposition and mineralization. Expression of COL1A2 mRNA in osteoblasts lining
      the outer periosteum of otic capsule is markedly higher than osteoblasts lining
      enchondral and endosteal layers, suggesting that differential expression may
      exist between osteoblasts lining endosteal, enchondral, and periosteal surfaces
      of bone in OI type II.

PMID- 17431986
TI  - Intravenous fluorescein vascularity studies of a new technique: the subcutaneous
      pedicled extension flap.
AB  - OBJECTIVE: To prove the vascularity of the subcutaneous pedicled extension flap
      through the subcutaneous pedicle. Second, the study was designed to reveal
      increasing vascularity as a function of time during the intraoperative period.
      DESIGN: Twenty-six cases of flap utility are presented. The last 11 of these
      cases were tested for intraoperative vascularity using intravenous fluorescein
      sodium. Following a 1-mL (100-mg) fluorescein sodium test dose, an additional 900
      mg was administered intraoperatively. The fluorescence was observed and
      photographed at 15-, 30-, and 60-minute intervals. The fluorescence (or lack
      thereof) was easily visible to the naked eye relative to the surrounding skin,
      requiring no specialized measurements. Photographic equipment consisted of a 35
      mm camera with a UV filter, using 400 ASA-rated film at a 1-second timed setting.
      A tripod was necessary. SETTING: All cases were performed in either an ambulatory
      surgical facility or an in-hospital facility. PATIENTS: All patients suffered
      from skin cancer requiring large resections, necessitating reconstruction via
      either grafts or flaps. INTERVENTION: Intravenous 10% fluorescein (Fluorescite)
      was used as a vascularity testing mode. The method was as described in the
      "Subjects and Methods" section. MAIN OUTCOME MEASURES: The results revealed
      conclusively the vascularity of the flap through the subcutaneous pedicle. In
      addition, the secondary goal, ie, of showing increasing vascularity with time,
      was also proved. RESULTS: The subcutaneous flaps have survived in all cases, with
      minimal complications. The intravenous fluorescein test, with timed applications
      intraoperatively, has been reaffirmed as an excellent prognosticator of
      survivability, as well as a confirmation of the innate vascularity of the
      subcutaneous pedicle. CONCLUSIONS: The subcutaneous pedicled extension is thought
      to be a new development in random flaps. Its vascularity via the subcutaneous
      pedicle has been conclusively confirmed using the safe and simple intravenous
      fluorescein intraoperative study. Second, increasing fluorescence on a timed
      basis has been reaffirmed and this degree of vascularity related to the ease of
      survival of the flap.

PMID- 17431987
TI  - Assessment and treatment of the paralyzed lower eyelid.

PMID- 17431988
TI  - Ischemic brain lesions in aged patients with dizziness.
AB  - OBJECTIVE: To compare neuro-otological test results in aged patients complaining
      of dizziness with their magnetic resonance imaging findings. DESIGN: The presence
      of lacunar infarcts of the hind-brain was used as a gold standard. SETTING: A
      department of otolaryngology in a regional general hospital. PATIENTS: All
      patients over 60 years old with dizziness during a period of 1 year 2 months,
      excluding those with central lesions of other than vascular origin (n=48).
      RESULT: Lacunar infarcts were found in 22 patients: the cerebellum for two
      patients, the brain stem for 17, and both regions for three. Patients with
      lesions of the cerebellum or the lower brain stem showed central vestibular
      abnormalities, whereas eight patients with only the upper brain-stem lacunae did
      not. A canal paresis was found in 12 of 20 patients with the brain-stem lacunae.
      Patients without lesions in the posterior fossa did not show significant
      abnormalities, indicating central disorders. CONCLUSION: This study documents a
      high prevalence of lacunar infarcts of the hindbrain in patients over 60 years
      old with dizziness, and it also demonstrates the difficulty in detecting small
      lesions of only the upper brain stem by neuro-otological tests. This calls
      attention to a differential diagnosis in aged patients with dizziness.

PMID- 17431989
TI  - Maxillary sinus hypoplasia, embryology, and radiology.
AB  - Maxillary sinus hypoplasia has been observed in up to 10% of radiological studies
      of the face or head. Although this may be a coincidental finding, it has been
      associated with chronic sinusitis and facial pain. Associated abnormalities of
      the lateral nasal wall, orbit, and ostiomeatal complex are common. The importance
      of this condition is, first, in the differential diagnosis of an "opaque"
      maxillary sinus and, second, as a potential hazard to the orbit of such patients,
      should they undergo functional endoscopic sinus surgery.

PMID- 17431990
TI  - Unusual presentations of lymphangioma.
AB  - L ymphangioma is a rare but potentially life-threatening disease, particularly in
      children. Three unusual cases of lymphangioma located in the infratemporal fossa,
      submaxillary gland, and cervicomediastinal regions are presented. These unusual
      sites illustrate that lymphangiomas may be found at sites distant from the
      locations of the embryological lymph sacs. The importance of radiological
      examination is emphasized. Although there are many modes of therapy for this
      disease, complete surgical excision when possible is advocated. The literature
      regarding the embryology, presentation, clinical workup, and current modes of
      therapy for lymphangioma is reviewed.

PMID- 17431991
TI  - Vestibular and audiometric consequences of blast injury to the ear.

PMID- 17431992
TI  - Cavernous sinus thrombosis: successful treatment using functional endonasal sinus
      surgery.
AB  - OBJECTIVE: Infections of the paranasal sinuses can be complicated by septic
      thrombosis of the cavernous venous sinuses. After standard antibiotic treatment,
      fewer than 50% of the patients recover completely, and the mortality rate is
      approximately 30%. We chose to treat this potentially catastrophic complication
      with functional endonasal sinus surgery in addition to standard antibiotic
      therapy. DESIGN: Case study. PATIENT: A 15-year-old boy presented to the
      emergency room of LeBonheur Children's Medical Center, Memphis, Tenn, with right
      proptosis, chemosis, ptosis, ophthalmoplegia, cranial nerve palsies, and
      paresthesia. The physical examination and computed tomographic scans of the
      sinuses and orbits revealed edema of the right orbit and pansinusitis, with
      secondary right cavernous sinus thrombosis and right superior ophthalmic vein
      thrombosis. INTERVENTION: The patient was started on a regimen of cefuroxime and
      nafcillin sodium and was scheduled for emergency functional endonasal sinus
      surgery to drain the primary sites of infection. After surgery, the patient was
      placed on a 3-week regimen of cefotaxime sodium, metronidazole hydrochloride,
      vancomycin hydrochloride, and heparin sodium. RESULTS: During surgery, the
      frontal recess and ethmoid, sphenoid, and maxillary sinuses were found to be
      filled with polypoid tissue and purulent material. Functional endonasal sinus
      surgery restored the sinuses to their normal physiologic state. The sinuses
      demonstrated the progress observed clinically. CONCLUSIONS: The improvement in
      outcome effected by standard antibiotic therapy can be significantly augmented by
      using functional endonasal sinus surgery in the treatment of cavernous sinus
      thrombosis.

PMID- 17431993
TI  - Pathologic quiz case 1. Sinus histiocytosis with massive lymphadenopathy (Rosai
      Dorfman disease).

PMID- 17431994
TI  - Hiccups and digital rectal massage.

PMID- 17431995
TI  - A new anesthetic for myringotomy.

PMID- 17431996
TI  - [Managing bradycardia in adults].
AB  - Bradycardia represents a common cause of requirement for specialist advice and it
      looks sometimes difficult to evaluate its pathological criteria and its medical
      management. The authors remind the physiological mechanisms and their
      aetiologies, cardiac or not. Many complementary exams can be employed but a
      rigorous strategy is necessary, based on the use of electrocardiogram, Holter
      ECG, implantable loop recorder, stress test, cardiac echography, tilt testing,
      electrophysiological study. Once the diagnostic established, the next fundamental
      step consists on a rigorous evaluation of severity in order to recognize the real
      urgency which require an hospitalization and to initiate rapidly the most
      appropriate treatment, sometimes before having the complete diagnosis, or to take
      in charge ambulatory the less severe cases all the more a reversible causes is
      identified. The situation often needs to take our time to avoid conceding too
      easily the definitive cardiac pacing. North American guidelines concerning
      cardiac pacing represent at least the references which we have to follow as often
      as possible particularly concerning atypical cases.

PMID- 17431997
TI  - [Lipid pneumonia].

PMID- 17431998
TI  - [Obsessive-compulsive disorder: frequent, invalidating and often accessible to
      treatment].

PMID- 17431999
TI  - [Clinical aspects of obsessive-compulsive disorder].
AB  - Obsessive-compulsive disorder is a frequent and chronic disorder accompanied by a
      marked distress and dysfunction. It is characterised by intrusive thoughts or
      images (obsessions) which increase anxiety, and by repetitive and ritualistic
      actions (compulsions) which decrease anxiety. Obsessive-compulsive disorder is
      frequently complicated by major depressive disorder or other psychiatrics
      disorders. Unfortunately, it is frequently underdiagnosed and undertreated
      despite the efficacity of treatments by selective serotonine reuptake inhibitors
      associated with behavioural and cognitive therapy. Diagnosis of this disorder is
      easy but needs a good knowledge of symptoms because of the clinical
      heterogeneity.

PMID- 17432000
TI  - [Comorbidity in obsessive-compulsive disorder].
AB  - It has been identified for a long time that obsessive-compulsive disorder (OCD)
      coexists with other psychiatric disorders: in over 50 percent of the OCD,
      patients meet the criteria for at least one axis I disorder (depression, anxiety
      disorders, eating disorders, impulse control disorders). Depressive disorders are
      the most commonly co-occurring difficulties and associated with significantly
      higher level of impairment and distress. Eating disorders and impulse control
      disorders are common comorbidity in OCD. These disorders as eating disorders,
      body dysmorphic disorder, trichotillomania, pathological gambling, share
      similarities in etiology, comorbidity, clinical features and treatment. Actually
      the notion of a spectrum of obsessive-compulsive related disorders is suggested
      by numerous studies.

PMID- 17432001
TI  - [Obsessive-compulsive disorder in children and adolescents].
AB  - Obsessive compulsive disorder (OCD) involves obsessions and compulsions that
      cause impairment and distress, and which interfere with children's developmental
      adaptation, daily functioning. Further more, OCD often disrupts peer and family
      relationships and school performance. One considered rare, recent epidemiological
      studies report prevalence rates ranging from 1% in prepubertal children to 3% in
      adolescents. Recently, significant advances have been made in understanding of
      the aetiology, pathophysiology, phenomenology, and treatment in children. The
      ongoing refinement of cognitive-behaviour and pharmacological treatment
      approaches has increased the likelihood that many youngsters with OCD will lead
      satisfying and relatively normal lives.

PMID- 17432002
TI  - [Treatment of obsessive-compulsive disorder].
AB  - Treatment of obsessive compulsive disorder has not changed a lot since 2000.
      Following a cautious assessment of the patient, using adequate scales, OCD
      patients require a step by step hierarchical treatment. A syndrome of low
      intensity (Yale-Brown Obsessive Compulsive Score [Y-BOCS] around 15) will be
      mainly treated by behavioural and cognitive therapy (BCT) especially exposition
      with prevention of response technique; for a more severe disorder, a drug
      treatment is required. Selective serotonin reuptake inhibitors (SSRI) are firstly
      recommended. They should be used in monotherapy with daily doses higher than
      those used for depression. Response is slow and usually delayed comparing to the
      alleviation of the depressive syndrome. A full response with disappearance of the
      symptoms is an exception. A good response to an antiobsessive treatment affords a
      50% reduction of the intensity of OCD. Clomipramine may be slightly more
      effective than SSRI. Once, an improvement has been obtained, the drug titration
      should be kept for at least 18 to 24 months before attempting to discontinue
      medication. In case of non response, switching SSRI drug, combination with BCT
      may contribute to resolve the problem. In treatment refractory OCD, combination
      with either risperidone or olanzapine has shown some effective results in
      controlled trials. Finally, for several infrequent patients with a "malignant
      syndrome", functional neuro-surgery using deep brain stimulation might be a safe
      and hopeful therapeutic technique.

PMID- 17432003
TI  - [Pathophysiological bases of obsessive-compulsive disorder and therapeutic
      implications].
AB  - Obsessive-compulsive disorder (OCD), relatively common anxiety disorder (2-3% of
      the general population), is characterized by persistent, intrusive and unpleasant
      thoughts, impulses or images and recurrent, time-consuming behaviours that are
      performed in a ritualistic fashion according to rigid rules and aimed at reducing
      anxiety and distress caused by obsessions. Significant progress in neuroscience
      over the last two decades has contributed to improve our knowledge about
      structure-function relations. Experimental neurophysiology in laboratory animals
      in parallel with advances in functional neuroimagery in humans, have provided
      precious information on the pathophysiological bases of OCD. From
      phenomenological considerations, several processes have been thought as disrupted
      in OCD, including monitoring of error detection, and emotional and motivational
      functions. Therefore, it has been postulated that the frontal-subcortical
      circuits originating in the orbito-frontal and the anterior cingulate cortices
      respectively, play a major role in the production of obsessive-compulsive
      symptoms because of their participation in the mediation of all these processes
      cited above. Such a pathophysiological approach of OCD is of special importance
      in the development of new strategies for treating OCD such as deep brain
      stimulation for instance, an innovative non-lesion neurosurgical procedure, which
      has recently been introduced in the management of severe, chronic forms of OCD
      resistant to conventional treatments.

PMID- 17432004
TI  - [Validity, effectiveness and other topics].

PMID- 17432005
TI  - [Type 1 diabetes of the child and adult].

PMID- 17432006
TI  - [Gait and balance disorders].

PMID- 17432007
TI  - [Acute respiratory distress in the newborn and the child (without foreign bodies
      of the upper respiratory tract].

PMID- 17432009
TI  - [Nutritional needs and food supplements in the adult. Evaluation of the
      nutritional state. Malnutrition].

PMID- 17432008
TI  - [Gastroesophageal reflux in infants, children and adults. Hiatal hernia].

PMID- 17432010
TI  - [Ibn an-Nafis contributions to the discovery of pulmonary circulation].

PMID- 17432011
TI  - Karo-Kari: disturbed psyche or wild ego?

PMID- 17432012
TI  - Helicobacter pylori infection in asymptomatic subjects in Makkah, Saudi Arabia.
AB  - OBJECTIVE: To determine the seroprevalence of Helicobacter.pylori antibodies in
      asymptomatic healthy population. METHODS: Convenient sampling was done in
      asymptomatic healthy individuals accompanying the patients who had no previous
      history of epigastric pain. Venous blood was collected from individuals and sera
      separated. Enzyme-linked immunosorbent assay (ELISA) was used to determine H.
      pylori IgG antibodies in all sera. RESULTS: A total of 396 samples were
      collected. H. pylori antibodies were found in 201 (51%) individuals. A 46%
      seroprevalence was found in subjects 15-20 years of age, which gradually
      increased with age and reached to .61% in subjects up to 50 years of age.
      Subjects > 40 years had higher antibody response than those < 40 years. There was
      no significant association between presence of H. pylori antibodies and dietary
      habits and sources of drinking water. H. pylori antibodies in female smokers were
      found in 9% and in non smoking females were 91% but no such difference was found
      in male smokers or non-smokers. CONCLUSION: Infection with H. pylori is prevalent
      in the healthy individuals of Makkah, Saudi Arabia. Infection is acquired in the
      early age and reaches up to 61% as the age advances. A nation wide
      epidemiological study is warranted to determine the seroprevalence of H. pylori
      in Saudi Arabia.

PMID- 17432013
TI  - Endoscopic management of biliary leaks after open and laparoscopic
      cholecystectomy.
AB  - OBJECTIVE: To evaluate the diagnostic and therapeutic efficacy of ERCP in the
      management of biliary leaks. METHODS: The study recruited 35 out of total 436
      ERCP patients with post surgical biliary leaks, who presented to our department
      between January 1, 2001 and September 30, 2004. Unsuccessful ERCP and/or
      completely transected CBD injuries were handed over to surgery. RESULTS: ERCP was
      successful in 33 (94%) patients. Of these 25 (75%) had cystic stump leaks, 3 (9%)
      had transected CBD, 2 (6%) had leakage from gall bladder (GB) bed, 2 (6%) had
      persistently draining T-tube with retained CBD stones and one (3%) patient had a
      leak from the right hepatic duct. CBD stenting was done successfully in 23 (92%)
      patients with a cystic stump leak. The other 3 patients with leakage from GB bed
      and right hepatic duct injury were successfully dealt with CBD stenting. The
      retained CBD stones were endoscopically removed. The overall therapeutic success
      was 93% and stents were removed after 6-8 weeks without further complications.
      Three patients with transected CBD were treated surgically. CONCLUSION:
      latrogenic Biliary system Injuries can be diagnosed and managed efficiently
      through Endoscopic Retrograde Cholangiopancreatography (ERCP).

PMID- 17432014
TI  - Preliminary experience with learner-centered evidence based format morning
      report.
AB  - OBJECTIVE: To observe the advantages of implementing learner - centered evidence
      based format morning report at King Abdulaziz National Guard Hospital, Alhasa,
      Saudi Arabia. METHODS: We modified conventional morning report by changing to a
      semicircular seating pattern to promote small group interactive discussions
      during case presentations. A facilitator was appointed to guide the sessions and
      asking problem based questions emanating from patient centered discussions. The
      question was formulated based on Evidence based medicine principles on a modified
      educational prescription and assigned to a volunteer to be answered in subsequent
      morning report sessions. Volunteers were asked to mention the search strategy,
      results and the evaluation of the process. The perceptions of the participants
      regarding the new format were assessed by a 17-statement questionnaire rated on
      Likert scale. RESULTS: A total of 46 different types of questions were asked
      during the initial 3-month period. All of them were answered. Participants
      utilized Medline and UpToDate the most to retrieve evidence. The commonest
      evidence retrieved were abstracts/journal articles followed by UpToDate articles.
      The new format was well perceived by the participants. CONCLUSION: Evidence based
      medicine can be applied successfully in the setting of morning report.
      Semicircular seating pattern and presence of facilitator promotes interactive
      discussions.

PMID- 17432015
TI  - Diagnostic importance of bone marrow examination in non-hematological disorders.
AB  - OBJECTIVE: To evaluate the frequency of involvement of bone marrow with non
      haematologic disorders and to observe the significance of bone marrow examination
      in establishing primary diagnosis of the same. METHODS: It was a descriptive
      study that extended from January 2003 to September 2005. A total of 4569 bone
      marrow aspirate and trephines were reported during this period. Only the non
      haematological disorders were analyzed for their clinical and laboratory
      parameter. RESULTS: During the study period, 63 patients (1.4%) were diagnosed to
      have non-haematological diseases detected primarily through bone marrow
      examination. The mean age of patients at time of procedure was 33 years (range 6
      months to 89 years), with male to female ratio of 3.2:1. Anaemia was the most
      frequent clinical finding followed by splenomegaly and weight loss. In adults
      metastatic tumors were the commonest disorder, followed by chronic granulomatous
      disease/reaction. However in children, storage disorders were more prevalent
      followed by haemophagocytosis as the second commonest non-haaematological
      disease. CONCLUSION: Metastatic solid tumors were the frequent non-hematologic
      disorder involving bone marrow in adult patients while storage diseases were most
      common among children. Hence, bone marrow examination is a useful laboratory tool
      in asserting the diagnosis of various non-haematological malignancies and other
      miscellaneous disorders.

PMID- 17432016
TI  - Chronic ITP: analysis of various factors at presentation which predict failure to
      first line treatment and their response to second line therapy.
AB  - OBJECTIVE: To observe the significance of various factors in chronic idiopathic
      thrombocytopenic purpura (ITP) which predict the response of first line
      (corticosteroids) and second line therapy (splenectomy) and to evaluate their
      response to second line therapy. METHODS: This was a descriptive, prospective
      study conducted from August 2004 till January 2006. Patients of all age groups
      and both genders with diagnosis of chronic ITP were included. Treatment protocol
      and criteria for response assessment was explained. RESULTS: During 17 months
      period, 86 patients with chronic ITP were analyzed. Non-responders to first line
      therapy were 74 patients who ultimately required splenectomy. Complete response
      (CR) was had in 37 (50.7%) patients, 10 (13.7%) and 27 (36.5%) had partial
      response (PR) and no response (NR) respectively. Analysis of variables like
      younger age, sex and low platelet count at presentation failed to show any
      significant influence on response to first line treatment. However response to
      splenectomy was found to be higher in patients who had initial complete or
      partial response with steroids and later relapsed and the platelet count was more
      than 300x10(9)/L on day 14 of surgery. CONCLUSION: Splenectomy remains the most
      effective treatment of chronic ITP. No significant factor was identified which
      predicted initial response to first line treatment. However patients who
      initially responded to steroids and had platelet counts above 300 X109/L about a
      fortnight after splenectomy showed promising results post-operatively (p=0.003
      and p=0.001).

PMID- 17432017
TI  - Role of misoprostol for therapeutic termination of pregnancy from 10 -28 weeks of
      gestation.
AB  - OBJECTIVE: To assess efficacy, safety and cost effectiveness of misoprostol
      (prostaglandin E1 analogue) for termination of pregnancy. METHODS: A descriptive
      study was conducted from March 2003 to December 2004, at Fauji Foundation
      Hospital Rawalpindi. A total of 200 patients, at 10-28 weeks of gestation,
      requiring termination of pregnancy were included. Each woman received first dose
      of 400 microg of misoprostol vaginally. Second dose of 400 microg of misoprostol
      was administered after 4 hours, according to the cervical dilatation, softening
      and uterine contractions. Oxytocin infusion was started after six hours of
      administration of first dose of Misoprostol, depending upon the uterine
      contractility. The process of abortion was monitored to assess the outcome
      measures. RESULTS: Successful abortion was seen in 137 (68%) patients, with
      induction to delivery interval of 12.2 hours. In 40 (20%) patients surgical
      evacuation was performed. Out of 40 patients, 27 (13.5%) underwent surgical
      evacuation due to incomplete abortion and 13 (6.5%) for excessive per-vaginal
      bleeding. A total of 23 (12%) patients had failure of method for induction of
      abortion and needed either repeat dose of misoprostol after 24 hours or other
      methods of induction (besides misoprostol). Side effects included nausea,
      vomiting, diarrhoea and fever. Mean hospital stay for induction of abortion was
      31 hours. CONCLUSION: Misoprostol is safe, efficacious and a cost effective drug
      for induction of the first and the second trimester abortions.

PMID- 17432018
TI  - Impact of intrauterine insemination as first line treatment of subfertility.
AB  - OBJECTIVE: To determine the success rate of intrauterine insemination (IUI) in
      couples presenting with subfertility following controlled ovarian
      hyperstimulation (COH) by the use of cost effective intrauterine catheter
      (insertion tube). METHODS: An experimental study was conducted at the Obstetric
      and Gynaecology Departments of Combined Military Hospital Kharian and PNS SHIFA
      Karachi in collaboration with the Department of Pathology from June 2002 to March
      2005. A total of 89 couples were studied, out of which 28 couples presented with
      abnormal finding in the seminal fluid of husband whereas in 61 couples no
      identifiable cause could be detected. The mean age of women was 29 years and the
      duration of infertility was variable. All women had tubal patency confirmed
      before undergoing COH. IUI was performed at follicular maturity of 18-22 mm. Main
      outcome measures analyzed were pregnancy rate per cycle of IUI, miscarriage rate
      and ongoing pregnancy rate. Prognostic factors associated with successful outcome
      in IUI, such as maternal age and motile sperm count was also observed. For cost
      effective measures, we used the sterilized disposable insertion tube of the
      'Copper-T 380 A' device for insemination of reated sperms into the uterine
      cavity. Chi-square test was applied to assess the effectiveness of IUI in
      relation with these variables. RESULTS: A total of 205 insemination cycles were
      performed resulting in achievement of pregnancy in 31 patients. Miscarriage
      occurred in 3 patients. Out of these 31 women who conceived, 21 (67.7%, p=0.003)
      were aged < 35 years with higher pregnancy rate per cycle (21 / 90 = 23.3%).
      CONCLUSION: Intrauterine insemination may be regarded as valuable procedure for
      couples presenting at younger age with lesser duration of infertility and
      unexplained subfertility.

PMID- 17432019
TI  - Third world issues in breast cancer detection.
AB  - OBJECTIVE: To determine the statistics for age, distributions of the type of
      mammography, ultrasonic evaluation, laterality, assessment category, risk
      factors, and financial status, amongst females undergoing mammography. METHODS: A
      descriptive review of consecutive records of women undergoing mammography during
      Janurary and February 2005 at a tertiary care cancer facility, the Shaukat Khanum
      Memorial Cancer Hospital and Research Center in Lahore, Pakistan. RESULTS: Of a
      total of 87 patients, only 12 had attended the hospital for mammographic
      screening. These 12 females could financially afford the cost of their images.
      The median age of all the females at the time of mammography was 47 years and the
      mode was 40 years. Of the total, 40 and 32 patients were found in assessment
      categories 1 and 2 respectively. Only 19 females underwent bilateral mammography
      whereas forty were evaluated further by ultrasound imaging. Sixteen women had
      family history of breast cancer among their first degree relatives, twenty eight
      gave history of Hormone Replacement Therapy and fifty could afford their entire
      imaging expenses. CONCLUSION: Most patients received their first mammograms when
      they already had clearly palpable disease. This was partly be due to economic
      reasons and mainly because of low level of awareness.

PMID- 17432020
TI  - Perioperative management of pheochromocytoma: anaesthetic implications.
AB  - Pheochromocytoma is a catecholamine producing tumour that can cause severe
      hypertension and other systemic disturbances. The perioperative management of
      pheochromocytoma remains a complicated anaesthesia challenge requiring intensive
      preoperative preparation and vigilant intraoperative and postoperative care. In
      this article the perioperative management of pheochromocytoma is reviewed by
      first summarizing its pathophysiology, clinical aspects and diagnosis, then
      highlighting the preoperative optimization of the patient and finally describing
      the intraoperative and postoperative anaesthetic management in the light of the
      current information.

PMID- 17432021
TI  - Epidemiology of erythema ab igne at a moderately cold weather station.
AB  - Erythema ab igne is a localized red brown reticular pigmentation, resulting from
      chronic, repetitive exposure to sub maximal heat, insufficient to cause burn. A
      study was carried out at the dermatology outpatient department of Combined
      Military Hospital, Abbottabad during January-April 2005 with the purpose to see
      frequency of erythema ab igne. Fourteen patients were identified, interviewed and
      examined in detail. Nine were females, eight of them housewives, and five were
      males. Age of the patients ranged from 9 to 60 years with a mean of 36.5 +/- 14.8
      years. Body Mass Index (BMI) of the patients ranged from 13.5 to 33.5, six of
      them were in the BMI range of between 25.1 and 30. Nine patients belonged to
      rural areas. Erythema ab igne was not associated with thyroid disease or any
      other systemic or psychiatric illness.

PMID- 17432022
TI  - Students' feedback of objectively structured clinical examination: a private
      medical college experience.
AB  - The aim of the study was to evaluate undergraduate students' perceptions
      regarding Objectively Structured Clinical Examination (OSCE) to be used as a
      feedback to improve the assessment technique. At the end of OSCE, students were
      provided with a feedback questionnaire related to OSCE to obtain their views and
      comments. The feedback was obtained from two consecutive batches of third year
      medical students and was utilized to incorporate the improvements in the process,
      wherever possible. A great majority of students (93% from group 'A' and 95% from
      group 'B') regarded OSCE as a practical and useful assessment tool in early years
      of medical education. In this study, students appreciated OSCE and offered
      constructive feedback on structure and organization of the process. However, at
      some stations they felt that instructions were ambiguous and time allocation was
      inadequate for the assigned tasks. The overall feedback was very useful and
      facilitated a critical review of the process.

PMID- 17432023
TI  - Klippel Trenauny Syndrome.
AB  - Klippel Trenauny Syndrome is a rare congenital syndrome characterized by port
      wine stain (capillary malformation), limb or hemihypertrophy and other vascular
      malformations. We present a case of this rare disorder in a young boy at an early
      stage of this disease.

PMID- 17432024
TI  - Emergency airway management of a patient with mediastinal mass.
AB  - Appropriate airway management is an essential part of anaesthesiologist's role.
      Extrinsic airway compression by rapidly growing mediastinal masses represents a
      therapeutic challenge to anaesthesiologists. We report a case of successful
      airway management in a patient with obstructed airway. The patient was a middle
      aged female who presented with severe respiratory distress secondary to a huge
      mediastinal mass. CT scan showed widened superior mediastinum with
      circumferential narrowing of trachea and left main bronchus. Her condition
      continued to deteriorate during her hospital admission, so emergency intubation
      and tracheostomy was planned. She was intubated with the help of a bougie using
      size 6 microlaryngoscopic tube after inhalational induction and mediastinal
      tracheostomy was done. Intraoperatively, there were few episodes of hypotension
      and desaturation, otherwise rest of intraoperative course remained uneventful.

PMID- 17432026
TI  - Death wish or suicidal ideation: implications for management.

PMID- 17432025
TI  - Collecting duct carcinoma: an incidental finding in a non functional kidney
      secondary to nephrolithiasis.
AB  - A nephrectomy specimen was sent to the laboratory for end stage renal disease
      secondary to nephrolithiasis. Initial sections incidentally revealed a tumor
      infiltrating the normal renal tissue. Further workup including cytochemical and
      immuno-histochemical stains confirmed it to be collecting duct carcinoma.

PMID- 17432027
TI  - Images in spine surgery: diffuse idiopathic skeletal hyperostosis (DISH).

PMID- 17432028
TI  - Liaison psychiatry and depression in medical inpatients.
AB  - OBJECTIVE: To assess the frequency of depression among hospitalized patients, the
      socio-demographic variables associated with depression and the number of cases
      referred by physicians to Psychiatry. METHODS: A cross-sectional study was
      carried out at the Aga Khan University Hospital Karachi. An anonymous Urdu
      version of the WHO-developed self-reporting questionnaire (SRQ) was administered
      to inpatients meeting the inclusion criteria. Data was analyzed by SPSS version
      13.0. RESULT: Of the 225 patients approached, 178 completed the questionnaire
      (men= 45.2%, women = 54.8%). The mean age of the sample was 45.2 years. Out of
      the total 30.5% of patients were identified as having probable depression, among
      which housewives were more likely to be depressed compared to others (p=0.031).
      Among variable comparison, there with secondary school education or below and
      those with psychiatric co-morbidities, showed significantly greater prevalence of
      depression (p=0.003) and (p=0.005) respectively. Attending physicians correctly
      diagnosed 7 (13%) patients and referred only 3 patients to Psychiatry over the
      previous month. CONCLUSION: The prevalence of depression among inpatients is
      comparable to that in the general population. Being a housewife, level at or
      below secondary school education and having a past psychiatric history are
      significant factors associated with depression in medical inpatients. A very
      small number of depressed cases were referred to a psychiatrist.

PMID- 17432029
TI  - Neonatal convulsions secondary to paroxetine withdrawal.

PMID- 17432030
TI  - Prevalence of cardiovascular events in diabetic patients taking sulphonylureas:
      need for assessment.

PMID- 17432031
TI  - Restless legs syndrome: common but frequently unrecognized disorder in pregnancy.

PMID- 17432032
TI  - The second century-- frustrations or challenges?

PMID- 17432033
TI  - Part VII. Macrolides, azalides, ketolides, lincosamides, and streptogramins.
AB  - In this article we describe antimicrobials that are grouped by their similar
      mechanism of action, namely inhibition of protein synthesis at the bacterial 50S
      ribosomal subunit. Macrolides, azalides, and ketolides are primarily used to
      treat community acquired respiratory tract infections. A lincosamide antibiotic,
      clindamycin, is primarily used to treat anaerobic infections. A combination of
      streptogramins, quinupristin/dalfopristin, is used to treat infections due to
      multiple drug resistant Gram positive cocci.

PMID- 17432034
TI  - Utilization of Unused Prescriptions Medication Act.
AB  - The ability to re-use prescription medications under appropriate safeguards for
      the care of the indigent is an idea that is catching hold in many states.
      Oklahoma has had a pilot program in Tulsa County under the authority of the
      Utilization of Unused Prescription Medications Act. Due to its success, it now
      seems appropriate to expand it to other counties and perhaps state wide.

PMID- 17432035
TI  - Disruption of the inferior popliteomeniscal ligamentous fascicle.
AB  - The superior popliteomeniscal ligamentous fascicular injury association with
      lateral meniscal injury has been previously documented in the literature. Both
      superior and inferior popliteomeniscal ligamentous injuries have demonstrated
      associations with lateral meniscal motion, and these ligaments can be disrupted
      in posterolateral corner knee injuries as well. The current case demonstrates an
      unusual case of isolated inferior popliteomeniscal ligamentous fascicular injury.
      We examine and discuss its association with the superior popliteomeniscal
      ligament, posterolateral corner injuries and the fascicular relationship to
      lateral meniscal tears.

PMID- 17432036
TI  - Pregnancy: a glimpse into a woman's future health.

PMID- 17432037
TI  - Pathogenesis of a Thai strain of white spot syndrome virus (WSSV) in juvenile,
      specific pathogen-free Litopenaeus vannamei.
AB  - White spot syndrome virus (WSSV) causes disease and mortality in cultured and
      wild shrimp. A standardized WSSV oral inoculation procedure was used in specific
      pathogen-free (SPF) Litopenaeus vannamei (also called Penaeus vannamei) to
      determine the primary sites of replication (portal of entry), to analyze the
      viral spread and to propose the cause of death. Shrimp were inoculated orally
      with a low (10(1.5) shrimp infectious dose 50% endpoint [SID50]) or a high (10(4)
      SID50) dose. Per dose, 6 shrimp were collected at 0, 6, 12, 18, 24, 36, 48 and 60
      h post inoculation (hpi). WSSV-infected cells were located in tissues by
      immunohistochemistry and in hemolymph by indirect immunofluorescence. Cell-free
      hemolymph was examined for WSSV DNA using 1-step PCR. Tissues and cell-free
      hemolymph were first positive at 18 hpi (low dose) or at 12 hpi (high dose). With
      the 2 doses, primary replication was found in cells of the foregut and gills. The
      antennal gland was an additional primary replication site at the high dose. WSSV
      infected cells were found in the hemolymph starting from 36 hpi. At 60 hpi, the
      percentage of WSSV-infected cells was 36 for the epithelial cells of the foregut
      and 27 for the epithelial cells of the integument; the number of WSSV-infected
      cells per mm2 was 98 for the gills, 26 for the antennal gland, 78 for the
      hematopoietic tissue and 49 for the lymphoid organ. Areas of necrosis were
      observed in infected tissues starting from 48 hpi (low dose) or 36 hpi (high
      dose). Since the foregut, gills, antennal gland and integument are essential for
      the maintenance of shrimp homeostasis, it is likely that WSSV infection leads to
      death due to their dysfunction.

PMID- 17432038
TI  - Isolation and characterization of Scophthalmus maximus rhabdovirus.
AB  - A rhabdovirus associated with a lethal hemorrhagic disease in cultured turbot
      Scophthalmus maximus Linnaeus was isolated. The virus induced typical
      cytopathogenic effects (CPE) in 9 of 15 fish cell lines examined and was then
      propagated and isolated from infected carp leucocyte cells (CLC). Electron
      microscopy observations revealed that the negatively stained virions had a
      typical bullet-shaped morphology with one rounded end and one flat base end. The
      bullet-shaped morphology was more obvious and clear in ultrathin sections of
      infected cells. Experimental infections also indicated that the S. maximus
      rhabdovirus (SMRV) was not only a viral pathogen for cultured turbot, but also
      had the ability to infect other fish species, such as freshwater grass carp. A
      partial nucleotide sequence of the SMRV polymerase gene was determined by RT-PCR
      using 2 pairs of degenerate primers designed according to the conserved sequences
      of rhabdovirus polymerase genes. Homology analysis, amino acid sequence
      alignment, and phylogenetic relationship analysis of the partial SMRV polymerase
      sequence indicated that SMRV was genetically distinct from other rhabdoviruses.
      Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) analysis of
      the purified SMRV revealed 5 major structural proteins, and their molecular
      masses were estimated to be about 250, 58, 47, 42, and 28 kDa. Significant
      serological reactivity differences were also observed between SMRV and its
      nearest neighbor, spring viremia of carp virus (SVCV). The data suggest that SMRV
      is likely a novel fish rhabdovirus, although it is closely related to
      rhabdoviruses in the genus Vesiculovirus.

PMID- 17432039
TI  - Antibody response of brown trout Salmo trutta injected with pathogenic
      Saprolegnia parasitica antigenic extracts.
AB  - Brown trout Salmo trutta injected with antigenic extracts from a pathogenic
      isolate of Saprolegnia parasitica developed specific antibodies that were
      detected by enzyme-linked immunosorbent assay (ELISA), immunofluorescence (IF)
      and Western blotting (WB), but not by immunodiffusion (ID). Three groups of five
      2 yr old brown trout were injected intraperitoneally with 3 different antigenic
      extracts: small hyphal fragments (HF) and soluble extracts from sonicated mycelia
      grown in medium with or without beta-sytosterol (SEB and SE, respectively). In
      the 2 groups injected with SE and SEB, antibodies were found in 66.7 % of the
      serum samples by ELISA, 54.5% by IF and 48.5% by WB. In the group injected with
      HF, only 1 trout survived the experiment, and in this fish only 1 sample was
      positive by ELISA. The results obtained by ELISA and IF were similar and show
      that there is cross-reaction between the antigens used. By WB, the proteins most
      frequently recognised were 2 proteins of 25 and 29 kDa. No significant
      differences were found in the groups injected with SE or SEB.

PMID- 17432040
TI  - Evaluation of a range of doses of ultraviolet irradiation to inactivate
      waterborne actinospore stages of Myxobolus cerebralis.
AB  - The ability of a range of doses of ultraviolet irradiation (UV) to inactivate the
      waterborne actinospore or triactinomyxon stages (TAMs) of Myxobolus cerebralis
      was evaluated by infectivity for juvenile rainbow trout Oncorhynchus mykiss. TAMs
      were UV-irradiated using a low pressure mercury vapour lamp collimated beam
      apparatus. All doses 40, 80, 120 and 160 mJ cm(-2) were found to completely
      inactivate the TAMs as demonstrated by the absence of microscopic lesions,
      myxospores and parasite DNA detected by quantitative PCR (qPCR) among rainbow
      trout 5 mo post-exposure. In contrast, rainbow trout receiving the same
      concentrations of untreated TAMs (1000 fish(-1)) developed clinical signs of
      whirling disease at 2 mo post-exposure and had severe microscopic lesions, high
      myxospore counts and high qPCR values when examined at 5 mo following exposure to
      the parasite.

PMID- 17432041
TI  - Infectivity of two nematode parasites, Camallanus lacustris and Anguillicola
      crassus, in a paratenic host, the three-spined stickleback Gasterosteus
      aculeatus.
AB  - Three-spined sticklebacks Gasterosteus aculeatus are frequent paratenic hosts of
      the nematode parasites Anguillicola crassus and Camallanus lacustris. As
      paratenic hosts, sticklebacks could spread infection by carrying high numbers of
      infective stages. In contrast, low infective ability of either parasite for the
      paratenic host could hinder the spread of infection. In the present study, G.
      aculeatus was, for the first time, infected under controlled laboratory
      conditions with defined doses of the parasites. Sticklebacks were exposed to 6,
      12, 18 and 24 parasite larvae to determine the infective ability of the 2
      nematode species. There were significantly higher infection rates for C.
      lacustris (18 to 49%) than for A. crassus (4 to 14%) at each exposure dose. In C.
      lacustris-infected sticklebacks, infection rates tended to be highest after
      exposure to 12 C. lacustris larvae and lowest after exposure to 24 parasites. In
      A. crassus-infected sticklebacks, no effect of parasite exposure dose on
      infection rates was observed. Immunity parameters such as respiratory burst
      activity and lymphocyte proliferation of head kidney leukocytes recorded 18 wk
      post exposure were not significantly affected by either parasite or exposure
      dose. Granulocyte:lymphocyte ratios were elevated only within the stickleback
      group showing the highest infection intensity of C. lacustris, i.e. to those
      exposed 18 parasites.

PMID- 17432042
TI  - First description of myxozoans from Syria: novel records of hexactinomyxon,
      triactinomyxon and endocapsa actinospore types.
AB  - Oligochaete worms collected in late March and early April 2005 from 3 freshwater
      biotopes in Syria were surveyed over an 11 wk period for myxosporean parasites
      (Myxozoa). Three types of novel actinospore stages were identified from 1 host
      species, Psammoryctides albicola. A hexactinomyxon was found in 6 P. albicola
      (7.5%) collected from a branch of the River Orontes, north of the city of Hama. A
      triactinomyxon and an endocapsa were found in single P. albicola specimens from
      the Al-Thaurah region of the Euphrates River (Lake Assad). No oligochaetes
      collected from Al-Ghab fish farm (Orontes region) released actinospores during
      the observation period. The present study is the first description of
      myxosporeans, including actinospore stages, from Syria. The 3 types described
      herein differ morphologically and molecularly (18S rDNA) from published records.

PMID- 17432043
TI  - Geographic risk factors for inter-river dispersal of Gyrodactylus salaris in
      fjord systems in Norway.
AB  - Gyrodactylus salaris has been recorded in 46 Norwegian rivers since 1975 and is
      considered a threat to Atlantic salmon stocks. The primary introductions of G.
      salaris (primary infected rivers) have been accounted for by specific events, as
      reported in the literature. The parasite has subsequently dispersed to adjacent
      localities (secondary infected rivers). The objective of this paper is to address
      the occurrence of secondary infections by examining the hypothesis of inter-river
      dispersal of G. salaris. A dispersal model for the secondary river infections via
      migrating infected fish is proposed. Due to the limited tolerance of G. salaris
      to salinity, both freshwater inflow to dispersal pathways and dispersal distance
      were expected to influence the probability of inter-river dispersal. Eighteen
      rivers were categorised as primary infected rivers, 28 as secondary infected
      rivers, and 54 as rivers at risk. Four risk factors: the log10 freshwater inflow;
      the dispersal distance; the time at risk; and the salmon harvest were combined in
      a multi-variable logistic regression model of the probability of secondary
      infection. The final multi-variable model included log10 freshwater inflow (Wald
      chi-square = 9.93) and dispersal distance (Wald chi-square = 6.48). Receiver
      operating characteristic analyses of the final model supported freshwater inflow
      as a strong predictor of G. salaris infection status. The strong influence of the
      freshwater inflow on the probability of secondary infection adds further support
      to the hypothesis of inter-river dispersal of G. salaris through fjords.

PMID- 17432044
TI  - Detection of rainbow trout antibodies against viral haemorrhagic septicaemia
      virus (VHSV) by neutralisation test is highly dependent on the virus isolate
      used.
AB  - Three serological tests, enzyme linked immunosorbent assay (ELISA), 50% plaque
      neutralisation test (50%PNT) and Western blotting (WB), were used to detect
      antibodies against viral haemorrhagic septicaemia virus (VHSV) in 50 rainbow
      trout broodstock from a rainbow trout farm endemically infected with VHS but with
      no clinical signs of infection. When the sera were examined by 50%PNT using the
      VHSV reference isolate DK-F1 or the heat attenuated DK-F25 mutant strain, no
      neutralizing antibodies were found. In contrast, when one of the virus isolates
      from the farm (homologous virus) was used in the 50%PNT, 90% of the fish were
      found to be positive. By examining a panel of different VHSV isolates in 50%PNT,
      it was demonstrated that the virus isolate used as test antigen could
      significantly affect the sensitivity and titre determination in 50%PNT for
      detection of rainbow trout antibodies against VHSV. When the sera were examined
      for the presence of VHSV antibodies by ELISA or WB, 61% were found to be
      positive. When conducting WB analysis, the viral glycoprotein was the protein
      most frequently recognized, followed by the viral nucleoprotein.

PMID- 17432045
TI  - Relationships among size, development, and Batrachochytrium dendrobatidis
      infection in African tadpoles.
AB  - The fungal pathogen Batrachochytrium dendrobatidis contributes to the global
      decline of amphibians. Although mortality from B. dendrobatidis infections occurs
      primarily in postmetamorphic individuals, infected tadpoles may suffer reduced
      growth and developmental rates as a result of oral chytridiomycosis, possibly
      affecting adult fitness. We conducted a field study in which we examined South
      African tadpoles for oral chytridiomycosis and compared the body sizes of
      infected and uninfected individuals of 2 species, Heleophryne natalensis and
      Strongylopus hymenopus. Presence of B. dendrobatidis was determined by
      microscopic inspection of mouthparts. Infection prevalence was high in both
      species, 62.5 and 38.6%, respectively, and infected individuals were
      significantly larger in both species. The inclusion of developmental stage in the
      analysis of S. hymenopus body size eliminated the relationship between body size
      and infection status, suggesting that differences in body size were not due to
      differences in growth, but to differences in developmental stage of infected
      larvae. These results suggest that larvae at more advanced developmental stages
      are more likely to be infected with B. dendrobatidis and that infection in larval
      amphibians may be dependent on time or developmental status of larvae. Contrary
      to the results of past studies, there was no evidence that oral chytridiomycosis
      resulted in decreased growth of tadpoles, despite the occurrence of oral
      abnormalities in infected individuals of 1 species. Because tadpole performance
      can subsequently affect the health of anuran populations and because tadpoles can
      act as reservoirs of infection, the study of B. dendrobatidis in larval
      amphibians is important to understanding the effects of this emerging disease.

PMID- 17432046
TI  - PCR assay for discriminating between infectious hypodermal and hematopoietic
      necrosis virus (IHHNV) and virus-related sequences in the genome of Penaeus
      monodon.
AB  - We developed a PCR assay that can detect infectious hypodermal and hematopoietic
      necrosis virus (IHHNV) but that does not react with IHHNV-related sequences in
      the genome of Penaeus monodon from Africa and Australia. IHHNV is a single
      stranded DNA virus that has caused severe mortality and stunted growth in penaeid
      shrimp. Recently, IHHNV-related sequences were found in the genome of some stocks
      of P. monodon from Africa and Australia. These virus-related sequences have a
      high degree of similarity (86 and 92% identities in nucleotide sequence) to the
      viral genome, which has often generated false-positive reactions during PCR
      screening of these stocks. For this assay, a pair of IHHNV primers (IHHNV309F/R)
      was selected. The sequences of these primers match (100% of nucleotides) the
      target sequence in IHHNV, but mismatch 9 or 12 nucleotides of the genomic IHHNV
      related sequences. This PCR assay was tested with various IHHNV isolates and with
      a number of samples of shrimp DNA that contained IHHNV-related sequences. This
      assay can reliably distinguish IHHNV DNA from shrimp DNA: it only detects IHHNV.
      Also, this pair of primers was included in a duplex PCR to detect IHHNV and
      simultaneously determine the presence of an IHHNV-related sequence. Using these
      primers, the PCR assay has a sensitivity equivalent to a PCR assay commonly used
      for detecting IHHNV in Litopenaeus vannamei, and can be used for routine
      detection.

PMID- 17432047
TI  - [Abnormal features of the sub renal portion of the inferior vena cava].
AB  - AIM: to determine the frequency of the abnormal anatomical features affecting the
      inferior vena cava (IVC). MATERIAL AND METHODS: we performed 161 dissections of
      the ICV on fresh (145) or formaldehyde-injected (16) cadavers. There were 86 men
      and 75 women. RESULTS: we found two abnormalities of the IVC: one left IVC in a
      woman and one double IVC in a man. These malformations can be explained by the
      embryology of the IVC. DISCUSSION: the frequency of abnormalities of the IVC is
      highly variable according to the studies: Richardson (1983) found 3% for the
      duplication of the IVC. Other malformations have been reported: double IVC, left
      IVC or right IVC with azygos prolongation. We never observed such associations in
      our study. Left IVC could be explained by the development of the left supra
      cardinal vein and by that of the left sub-cardinal and intercardinal anastomoses.
      Double IVC corresponds either to the development of the left supra-cardinal vein
      or to the persistence of the left cardinal vein or the left sub-cardinal vein.
      CONCLUSION: abnormalities of the ICV dysplay different anatomical features due to
      the complexity of the embryogenesis of this vessel; their frequency is far from
      being rare. Unknowing these abnormalities could lead to severe haemorrhages
      during surgical interventions on the retroperitoneal, cardiac or oesophageal
      regions.

PMID- 17432048
TI  - [Contribution to subscapularis nerve supply. 18 dissections].
AB  - INTRODUCTION: Dividing the subscapularis muscle along its fibers axis allows
      approaching the glenohumeral joint. The more medial its division, the more
      possible injury of its nerve supply. AIM: The aim of our study was to assess the
      subscapularis nerve supply through cartography of the entry points of
      subscapularis nerves from simple landmarks, reproducible by triangulation.
      MATERIAL AND METHODS: On 18 formalin-preserved shoulders, after dissection of the
      subscapularis nerves, distances were measured between entry points of
      subscapularis nerves and the following landmarks: center of the minor tubercle
      (tm), upper and lower poles of the glenoid cavity (cgs and cgi), apex of the
      coracoid process (pc). RESULTS: There were in average 3.33 subscapularis nerves
      (2-4). These different nerves split most often before entering subscapularis
      muscle; there were in average 5.05 entry points (3-6). Distances between entry
      points and clinical landmarks were as follows: cgs, 3.9-6.45 cm; cgi, 3.7-5.54
      cm; tm, 5.9-7.15 cm; pc, 4.9-7.66 cm. Reporting these measurements onto a frame
      allowed to show that all these points were located in average medially to the
      scapular notch and at more than 3 cm from the anterior border of the glenoid
      cavity. CONCLUSION: If the transverse division does not extend farther than 3 cm
      from the anterior border of the glenoid cavity and from the medial border of the
      root of the coracoid process, there should not be any injury of the subscapularis
      nerves.

PMID- 17432049
TI  - [3D reconstruction of anterior internal vertebral venous plexus of a human fetus:
      a feasibility study].
AB  - Anterior internal vertebral venous plexus have been studied extensively due to
      their clinical importance in diseases of the spine and obstruction of the
      inferior vena cava. The aim of this feasibility study was to reconstruct in 3D
      the lower thoracic area of the anterior epidural space of a 69 mm (crown-rump)
      human fetus from the Rouviere Collection, circa 1927. Forty slices (spaced by 40
      microm) at the level of the tenth and eleventh thoracic vertebrae, and their
      lower adjacent intervertebral discs, were reconstructed in 3D using the
      commercial software SURFdriver. In a preliminary study, we had found that the
      structures of the epidural space are already formed at this stage of development,
      and that they are comparable to the adult stage (2002). Reconstruction of the
      microscopic slices in 3D allowed to better visualize spatially the structures of
      the venous plexus and their anatomical relationships. This technique could be
      used as a complement to the classically used histological studies.

PMID- 17432050
TI  - Morphological and constitutional comparison of age-matched in-vivo and post
      mortem populations.
AB  - Cadaver studies are often used as a reference in clinical studies and in-vivo
      Body Composition (BC). However, there is a paucity of comparative information
      between in-vivo and post-mortem populations. Forty living volunteers for the
      study (18 males and 22 females, age range 55-92 years) were age-matched with a
      sample of 26 well-preserved cadavers (13 males and 13 females). Twenty eight
      anthropometric variables were chosen, i.e. nine circumferences, eight breadths,
      four lengths, five skinfolds, weight and height. These were measured both in vivo
      and post-mortem. All measures were taken according to Martin and Saller (1957),
      Clauser et al. (1969) and Clarys et al. (1984). Normality verification, Variant
      Analysis (one way Anova) and Mollison transformations were used for the
      comparative treatment. Data from this study confirm that the in-vivo and post
      mortem macro morphology are in agreement. The best similarities were found
      between the female groups. This study confirms that cadaver research is reliable
      for the validation of in-vivo techniques and as a reference standard in the
      absence of other direct validation measures.

PMID- 17432052
TI  - A rare case of bilateral sternocleidomastoid muscle variation.
AB  - An abnormal sternocleidomastoid (SCM) muscle was encountered bilaterally during
      routine dissection of the head and neck region of a 60 year old male cadaver. The
      SCM muscle of both the sides had an additional sternal head arising from the
      capsule of the sternoclavicular joint and the supero-lateral border of the
      manubrium sterni. The clinical significance of the present variation is immense,
      as it might cause difficulty in assessing the vital neurovascular structures of
      the neck during surgical procedure.

PMID- 17432051
TI  - [Cecal volvulus: anatomical bases and physiopathology].
AB  - The aim of this study was to report on 7 cases of cecal volvulus and to evaluate
      anatomical variations allowing this pathology. METHODS: 7 consecutive patients (4
      women) treated for cecal volvulus were included. The clinical and paraclinical
      parameters, the management of patients, were studied through an analysis of
      medical histories. Contributing factors for cecal volvulus were analysed by an
      anatomical study and literature analysis. RESULTS: all patients complained about
      abdominal pain associating or not to acute intestinal obstruction. The diagnosis
      was radiographically carried out for 3 patients. All patients were treated by
      surgical procedures (right colectomy: n = 6, cecopexy: n = 1). The mortality and
      morbidity rates were 0 percent and 28 percent. Fifteen anatomical subjects had
      complete dorsal fixation (75 percent). Seven out of them had retrocecal recessus.
      Five subjects (25%) had a non fixed cecum, according to the literature relating a
      non-fixation of ascending colon to parietal peritoneum in 11 to 25 percent of the
      cases. The main factor of risk is the female gender. CONCLUSION: cecal volvulus
      can be advocated for patients having abdominal pain. The diagnosis is rarely
      based on an only clinical examination or abdominal radiographs alone.
      Tomodensitometry is most performing examination for diagnosis. An early and
      appropriate management of patients is necessary to avoid significant morbidity
      and mortality rates.

PMID- 17432053
TI  - Trends and challenges in the effective and sustainable control of Haemonchus
      contortus infection in sheep. Review.
AB  - Haemonchosis, with its very wide distribution, has become a very important
      production constraint in sheep farms in tropical, subtropical and temperate
      regions worldwide. Various intrinsic and extrinsic factors determine the survival
      of Haemonchus contortus and hence the development of the disease in the animal.
      In general, control of gastrointestinal nematode infestation in sheep relies
      heavily on anthelmintic treatments. However, the indiscriminate use of these
      drugs has led to the widespread emergence of drug resistant strains of parasites,
      that has necessitated the development and use of various parasite control methods
      such as grazing management, biological agents and vaccines and the selection of
      resistant breeds of animals, with or without moderate use of anthelmintics. The
      ultimate goal of such control programs is to enhance productivity, while
      minimising risks regarding drug resistance and consumer and environmental
      concerns. This review attempts to highlight the different methods employed in the
      control of haemonchosis in sheep and the practical limitations associated with
      both control programs and the internal and external factors associated with the
      parasite and its microenvironment.

PMID- 17432054
TI  - [Worldwide human zoonotic cryptosporidiosis caused by Cryptosporidium felis].
AB  - Cryptosporidium is an important enteric pathogen worldwide distributed causing
      diarrhoeal illness in humans and animals. Identifying Cryptosporidium species
      using conventional criteria, such as oocyst morphology, is inadequate. The advent
      of molecular techniques has conducted to characterize different species and
      genotypes of Cryptosporidium infecting humans. The vast majority of human cases
      of cryptosporidiosis in the world are caused by both species, Cryptosporidium
      hominis and Cryptosporidium parvum. However other species including
      Cryptosporidium felis can infect humans too. In this review, we analyse 58
      reported cases of human C. felis infection in different parts of the world. To
      date this emerging protozoan disease is present in humans around the world,
      except in Australia and Oceania. Adults and children are infected, more often
      when immunocompromised by HIV infection (83 % of reported cases). Apparently
      immunocompetent individuals are also infected by C. felis. In developing
      countries, inhabitants are more likely infected by C. felis probably through the
      oocyst contamination of drinking or recreational water. The public health
      importance of C. felis infection in tropical countries remains to be evaluated.

PMID- 17432055
TI  - [Probable speciations by "host-vector 'fidelity'": 14 species of Plasmodium from
      magpies].
AB  - 33 Magpies resident in two parks close to Paris were investigated for the
      presence of Plasmodium parasites. The majority of the birds were found to be
      infected with multiple parasite species. A total of 14 species were observed, and
      of these 10 were novel and consequently described, and two could not be assigned
      with confidence. It is hypothesized that the unexpected abundance of species is
      due to a phenomenon which we term "host-vector 'fidelisation'". Indeed, the
      combination of the eco-biological characteristics of the host (mating pairs in
      contiguous, but strictly defined territories) with those of the vector (numerous
      Aedes species with distinct behavior), would generate fragmentation of the
      niches. This type of isolation overlays others known for parasitic populations
      (geographical, circadian, microlocalisations), leading to the formation of
      independent host-parasite niches which in turn lead to speciation.

PMID- 17432056
TI  - Larval trematodes (Digenea) of the great pond snail, Lymnaea stagnalis (L.),
      (Gastropoda, Pulmonata) in Central Europe: a survey of species and key to their
      identification.
AB  - A survey of cercariae and metacercariae (Trematoda, Digenea) from the great pond
      snail (Lymnaea stagnalis) in Central Europe (Austria, Czech Republic, South-East
      Germany, Poland and Slovak Republic) is presented, based on a study of 3,628
      snails examined from 1998 to 2005. A total of 953 (26.3%) L. stagnalis were
      infected with 24 trematode species comprising 19 species of cercariae and 11
      species of metacercariae (six species occurred both as cercarie and metacercarie)
      of eight families. The dominant cercariae were those of Opisthioglyphe ranae (159
      hosts infected), Plagiorchis elegans (141) (both family Plagiorchiidae) and
      Echinoparyphium aconiatum (153) (Echinostomatidae); 14 double infections were
      found. The most frequent metacercariae were those of Neoglyphe locellus (71)
      (Omphalometridae), E. aconiatum (66), Echinostoma sp. (59) and Moliniella anceps
      (48) (Echinostomatidae). In the previous studies carried out in Central Europe, a
      very similar spectrum of nine trematode families of 22 cercariae determined to
      species level and 43 types of cercariae reported under generic or provisional
      names, which can be in many cases conspecific with the previous taxa, were found.
      A simple key to identification of cercariae and metacercariae, together with
      their illustrations, is provided.

PMID- 17432057
TI  - Trichostrongylina (Nematoda) from Malagasy Muridae. III--description of a new
      species of Heligmonoides Baylis, 1928 (Heligmonellidae) parasitic in Mus
      musculus.
AB  - Heligmonoides variabilis n. sp. (Heligmosomoidea, Nippostrongylinae) a parasite
      of Mus musculus from Madagascar is related to H. afghanus (Tenora, 1969), H.
      ikeharai Hasegawa, 1990 and H. josephi (Wertheim & Durette-Desset, 1976), all
      having the dorsal ray divided anterior to the arising of rays 8. H. ikeharai a
      parasite of Tokudaia muenninki (Muridae) from Japan is the most closely related
      species with rays 8 arising at mid-length along the dorsal ray. It is
      differentiated from the new species by very long spicules (almost half of body
      length) and by the length of the vestibule (almost one millimeter). A new
      definition of the genus Heligmonoides Baylis, 1928 is proposed with a dichotomic
      key of the species. The biogeographic distribution and the host spectrum of the
      genus are described.

PMID- 17432058
TI  - Prevalence and intensity of Angiostrongylus cantonensis in freshwater snails in
      relation to some ecological and biological factors.
AB  - The purpose of the study was to record different intermediate hosts of A.
      cantonensis and to determine the infection prevalence and intensity of this
      parasite in freshwater snails in relation to some ecological and biological
      factors. The study was conducted at Al-Salam irrigation Canal and Al-Abtal
      village (north Sinai) for one year, from March 2004 to February 2005. Thirteen
      species of freshwater snails of nine families were examined for A. cantonensis
      infection. Six species were found infected with A. cantonensis larvae. These
      species were L. carinatus, C. bulimoides, C. cyclostomoides, B. alexandrina, L.
      natalensis and M. tuberculta. The infection prevalence of A. cantonensis in the
      examined snails ranged from 0.63 to 2.24%. L. carinatus snail had the highest
      prevalence, mean abundance and mean intensity of A. cantonensis infection.
      Positive correlations were found between both prevalence and mean abundance of A.
      cantonensis and host size in L. carinatus and M. tuberculata. Negative
      correlations were detected between salinity and prevalence, mean abundance and
      mean intensity of larvae of A. cantonensis. The results demonstrated seasonal and
      spatial variation in the prevalence, mean abundance and mean intensity of
      infection among examined snails. In this study, A. cantonensis larvae were found
      in a wide range of freshwater snails and M. tuberculata snail was recorded as a
      new intermediate host for the first time. In conclusion, further investigations
      in other areas and controlled laboratory experiments of infection approaches are
      required to evaluate the possible threat of this parasite on humans.

PMID- 17432059
TI  - Proliferative peritoneal and pleural cestodiasis in a cat caused by metacestodes
      of Mesocestoides sp. Anatomohistopathological findings and genetic
      identification.
AB  - A 10-year-old female cat was brought to Istituto Zooprofilattico Sperimentale
      delle Regioni Lazio e Toscana for post-mortem examination. The animal used to
      live, together with 26 other cats, in the big terrace of an apartment at the 8th
      floor in Rome; and was always fed with industrial pet food. Anamnesis referred
      balance troubles, vomit and convulsions, during a couple of days, followed by
      sudden death. At necropsy, the cat presented mucoid rhinitis, purulent
      tracheitis, small areas of pneumonia, dark spots in the liver, catarrhal
      hemorrhagic gastritis, fibrinous enteritis and meningeal hyperemia. Thoracic and
      abdominal cavities were completely invaded by hundreds of larval stages of
      cestodes. The same parasites were also included in nodules in pancreatic, lung
      and kidney parenchyma. Microscopic examination of parasites allowed their
      identification as larval stages (metacestodes) of cestodes of the genus
      Mesocestoides. The molecular genotyping of the metacestodes indicates a close
      relationship with members of the genus Mesocestoides, although a significant
      variation was found with respect to the available sequences of other species of
      the genus.

PMID- 17432060
TI  - [Experimental infection of goats with Schistosoma bovis and S. curassoni:
      comparative pathogenic effects].
AB  - Specific mortality and morbidity have been quantified in goats experimentally
      infected with Schistosoma bovis or S. curassoni strains from Niger. The study
      involved nine animals followed during 380 days after infection with,
      respectively, 1,800 or 2,400 cercariae. S. bovis was significatively more
      pathogenic than S. curossoni in terms of mortality, weight loss and packed cell
      volume decrease. In addition, the intensity of clinical symptoms was
      significatively and positively correlated to the levels of fecal egg excretion.
      Compared to non-infected controls, a growth differential of, respectively, 1,600
      and 880 grams per month should incite to consider S. bovis and S. curassoni as
      parasites of serious economical impact in sahelian countries.

PMID- 17432061
TI  - Sinus headaches.

PMID- 17432062
TI  - Biofilms and chronic rhinosinusitis: systematic review of evidence, current
      concepts and directions for research.
AB  - INTRODUCTION: Chronic rhinosinusitis (CRS) possesses the hallmarks of biofilm
      mediated disease. This paper represents a systematic review of the published
      evidence for biofilms as the mediator of the inflammation in CRS. Current
      concepts on biofilm formation and properties, treatment strategies and directions
      for research are discussed. METHODS: A systematic review of the published
      literature for biofilms and their role in chronic rhinosinusitis was undertaken.
      Both Medline (1966-2006) and Embase (1988-2006) were searched until November 2006
      which yielded 652 articles, 13 of which provided original research of biofilms in
      CRS. RESULTS: There were 7 studies demonstrating biofilm morphology in mucosal
      samples from human CRS patients. One study showed similar evidence for biofilms
      in an animal model of CRS. FISH techniques with CLSM were employed in one study
      to demonstrate biofilm formation in situ by S. pneumoniae, S. aureus, H.
      influenza and P. aeruginosa. In vitro biofilm forming capacity of microbiological
      samples, after culture, was assessed in two studies. Correlation with a clinical
      outcome was also made in these papers. One study demonstrated biofilm growth in
      removed frontal sinus stents. CONCLUSIONS: Biofilms are associated with CRS,
      however, little research is available to define their role in the pathogenic
      process. There is tremendous potential for future research. Biofilms may be a
      significant factor in the inflammatory process.

PMID- 17432063
TI  - Endoscopic sinus surgery for 'sinus headache'.
AB  - The relationship between sinus disease and headache is complicated. We undertook
      a prospective study to examine the success of endoscopic sinus surgery for the
      alleviation of headache in a defined group of individuals. In particular we
      wished to discover whether the presence of asthma, nasal polyposis and purulent
      rhinosinusitis indicated that surgical intervention achieved any greater relief
      of symptoms compared to those without these conditions. Overall we found a
      significant improvement in headache symptoms after endoscopic sinus surgery, but
      subgroup analysis of patients with or without asthma, nasal polyposis and
      purulent rhinosinusitis showed no differences between the groups.

PMID- 17432064
TI  - Evaluation of an anatomic model of the paranasal sinuses for endonasal surgical
      training.
AB  - OBJECTIVES: To assess the suitability of a new anatomic model of the paranasal
      sinuses for endonasal surgical training. STUDY DESIGN: Prospective observational
      pilot study. METHODS: A new anatomic model of the paranasal sinuses was developed
      by the Department of Anatomy at the University of Zurich. The practicability of
      the model was evaluated by three experienced endoscopic sinus surgeons with a
      special focus on its possible use in training. Standardized surgical procedures
      were performed under simulated real-life conditions in the operating theatre.
      RESULTS: The endoscopic appearance of the nasal airway closely resembled real
      human tissue and the detailed anatomy of the model allowed the same structured
      surgical steps to be performed as in real life in the absence of bleeding.
      CONCLUSION: This anatomic model is a readily available teaching tool for
      endoscopic sinus surgeons.

PMID- 17432065
TI  - Endonasal endoscopic resection of juvenile nasopharyngeal angiofibroma.
AB  - Juvenile angiofibroma (JNA) is a rare benign but locally aggressive tumour of the
      nasopharynx that primarily occurs in adolescent males. We report a series of 6
      consecutive cases operated by exclusive endoscopic approach between from March
      1996 and June 2003. All were male. The mean age was 17.2 years old (range: 11-23
      years). The tumour involved the nasopharynx in all the cases (6/6), the sphenoid
      sinus (3/6) and the medial part of the pterygopalatine fossa (4/6). According to
      Radkowski's classification (Table 1), one patient was stage Ia, one was stage Ib
      and four patients were stage IIb. The mean duration of the surgery was 2 hours.
      The mean intraoperative blood loss was 575 ml despite a preoperative
      hyperselective embolization. The mean follow-up after the first operation was 67
      months. All patients but one were free of disease. One patient had a recurrence
      in the nasopharynx and sphenoid sinuses requiring a successful revision procedure
      3 years after the primary surgery. Another patient presented with a 5 mm non
      symptomatic nodule in the pterygopalatine fossa, regressing on MRI during the 4
      years following the surgery. In conclusion, endoscopic resection of JNA is a
      difficult but effective operation in experienced hands. Based upon the recent
      international literature, endonasal surgery combined with a preoperative
      embolization of the arterial supply is indicated for small and middle size JNAs
      but also for large tumours extended to the pterygopalatine fossa and medial
      aspect of the infratemporal fossa. Minimal intracranial extension is not an
      absolute contraindication if there is no clinical or radiological involvement of
      the cavernous sinus. A tridimentional guiding system can be of some help in large
      tumours.

PMID- 17432066
TI  - Surgical approaches for nasal dermal sinus cysts.
AB  - Nasal midline masses of ectodermal origin include nasal dermoids (ND) and nasal
      dermal sinus cysts (NDSC). NDSC are characterized by an intracranial-extradural
      extension, while ND are limited to the nasal dorsum, medial canthus, or glabella
      without intracranial extension. We report our experience in 11 NDSC patients. The
      goal of this study is to present the management including surgical technique for
      NDSC and compare it with the literature. Because a transfacial approach for NDSC
      with vertical incision caused visible scarring in two out of three patients, we
      applied a new surgical approach in four patients. This approach consisted of a
      simple excision and mobilisation of the pit while the proximal part is resected
      using a coronal transfrontal approach. The relation of the nasal fistula to the
      nasal bone is essential considering osteotomy. Disruption of the bony
      cartilaginous junction of the nasal dorsum must be prevented to avoid later
      growth impairment of the nose. There was no recurrence of NDSC in all 7 operated
      patients after a mean follow-up of 3.9 years (range 0.5-7.2 years).

PMID- 17432067
TI  - Reference values for acoustic rhinometry in decongested school children and
      adults: the most sensitive measurement for change in nasal patency.
AB  - INTRODUCTION: Only a limited reference material for acoustic rhinometry (AR)
      exists for school children most often calculated as the minimum cross-sectional
      area (MCA) in the non-decongested nose. We want to establish a set of reference
      values for MCA and nasal volumes for both adults and children and include values
      also for the decongested nose and determine the most sensitive measurement for
      change in nasal patency. METHOD: Data from two studies were used; one comprising
      of 53 (20M, 33F) school children, age 9-11 years, and one comprising 146 (127M,
      19F) healthy workers in the wood industry. Measurements by acoustic rhinometry
      were done before and after decongestion with two puffs of oxymethazoline nasal
      spray (1 mg/ml). RESULTS: We found the decongested nasal volume (2-5 cm) to be
      3.71 cm3 (3.58-3.84) in school children and 5.44 cm3 (5.21-5.67) in adults. We
      found the volume from 2-5 cm into the nasal cavity to be the most sensitive
      measure of change in nasal patency by decongestion, and MCA to be the least
      sensitive in both adults and children. DISCUSSION: A larger study population of
      children, covering a broader range of age, is needed to stratify for gender and
      height. Our data in adults are in accordance with previous findings. CONCLUSION:
      We have provided a reference material for acoustic rhinometry in school children
      and adults. Future evaluation of change in nasal patency should contain
      information about nasal volume from 2-5 cm into the nasal cavity and not just MCA
      in adults and school children.

PMID- 17432068
TI  - Use of nasal provocation test in the diagnostics of occupational rhinitis.
AB  - OBJECTIVES: The purpose of the study was to evaluate the usefulness and clinical
      value of the nasal provocation test (NPT) with various allergens and non-IgE
      mediated irritants in the diagnostics assessing occupational rhinitis. METHODS: A
      large number nasal provocation data from patients with suspected occupational
      rhinitis was evaluated retrospectively. The results of nasal provocation tests
      with different agents, as well as the correlation of nasal scoring to weighed
      mucus secretion, were analyzed. RESULTS: Altogether 507 NPTs were done in three
      years in 165 persons. In total, 39% of the allergen provocations (125/318) were
      positive. The most common positive reactions were against flours, animal
      epithelia, storage mites and various plants. Wood dusts, mainly through non-IgE
      mediated reactions, gave 50% positive results. Positive NPTs to moulds were
      observed mainly in sensitized patients. Altogether, 10% of the control
      provocations were positive. The weighting of mucus secretion added sensitivity of
      NPT. CONCLUSIONS: The NPT is an essential standard tool in the diagnostics of
      allergic occupational rhinitis; however it needs to be evaluated in the context
      of the medical and work history and knowledge of sensitization. Although
      expensive and laborious, NPT is safe and easy for the patient. We still need
      reliable diagnostic tools for non-allergic work-related rhinitis.

PMID- 17432069
TI  - Paediatric periorbital cellulitis and its management.
AB  - TOPIC: Periorbital cellulitis is often difficult to distinguish from orbital
      cellulitis, which is a rare but potentially fatal disease. There are only a few
      small studies in the literature and we aim to look at an ideal way of managing
      periorbital cellulitis in a paediatric population using our department's
      experience. MATERIALS AND METHODS: Retrospective analysis of case notes and
      computer records of children attending our hospital with periorbital cellulitis
      over 26 month period. RESULTS: Thirty-four patients met the criteria. Sixteen
      patients had reduced visual acuity, proptosis or ophthalmoplegia. Twenty-three
      had white cell count checked, 14 were raised and 7 of these had an operation.
      Eleven had blood cultures checked and all were negative. Seven had other cultures
      taken, Streptococcus milleri was the predominant organism isolated. Sixteen were
      CT scanned, 14 showed significant sinus disease. All patients were treated with
      intravenous antibiotics and ten required operative intervention. Two patients
      developed lateral orbital collections requiring further surgery. CONCLUSIONS:
      Although relatively rare, periorbital cellulitis can be dangerous and it is
      essential for it to be treated seriously. A multidisciplinary approach is needed
      in managing children with this condition, with a good history and full blood
      count assisting in assessing severity, but a CT scan of the patient's sinuses is
      essential to differentiate from orbital cellulitis.

PMID- 17432070
TI  - Prevalence of parosmia: the Skovde population-based studies.
AB  - AIM: Parosmia can be defined as a qualitative odor distortion. Despite the
      consequences of this condition for quality of life, the scientific literature
      lacks information about the prevalence of parosmia in the general population,
      which was the objective of the present study. METHODS: Random samples of 1,900
      adult and 401 teenage inhabitants, stratified for age and gender, were drawn from
      the municipal population register of Skovde, Sweden. In total, 1,713 individuals
      (74% of the samples) agreed to participate, of which 1,387 (73%) were adults and
      326 (81%) were teenagers. They responded to a question about parosmia by means of
      either a structured interview (adults) or a questionnaire (teenagers). RESULTS:
      The overall prevalence of parosmia was 3.9% (4.0% in adults and 3.4% in
      teenagers), which was stable across gender, but differed somewhat between age
      groups, with highest prevalence in the age group 20-29 years. CONCLUSIONS: The
      rather high overall prevalence, 3.9%, does indeed suggest that parosmia deserves
      attention when attempting to better understand olfactory dysfunction in clinical
      settings and in the general population of both adults and teenagers.

PMID- 17432071
TI  - The validity of CCCRC test in patients with nasal polyposis.
AB  - Both the Connecticut Chemosensory Clinical Research Center (CCCRC) test and Cross
      Cultural Smell Identification Test (CC-SIT) are used to assess the sense of smell
      in patients all over the world. Our aim is to know whether the CCCRC test is a
      valid olfactory test in comparison with CC-SIT. Therefore, we have done a
      prospective study in 60 adult patients with nasal polyposis to compare the
      validity of CCCRC with UPSIT. We used the CCCRC olfactory test made up of a
      threshold and suprathreshold test while CC-SIT relies solely upon suprathreshold
      measurement. We determined the specificity, sensitivity, positive predictive
      value and negative predictive value for patients suffering nasal polyposis with
      the CCCRC test. The validity index was 95% and accuracy rate was 8%. We
      determined unit cost and the reliability of the CCCRC test. For patients with
      nasal polyposis: the sensitivity was 86%; the specificity was 94%; the positive
      predictive value was 93% and the negative predictive value was 88%. The
      reliability was 92%. The unit cost of the CCCRC was 5.60 euro. The CCCRC test is
      a valid test in comparison with CC-SIT. CCCRC is cheap and can be used in routine
      clinical settings.

PMID- 17432072
TI  - Evaluation of efficacy of topical corticosteroid for the clinical treatment of
      nasal polyposis: searching for clinical events that may predict response to
      treatment.
AB  - The objective of the present study was to evaluate the clinical response to
      topical budesonide in patients with nasal polyposis (NP) and to evaluate if there
      is any clinical event that may predict the response to treatment. Twenty patients
      with NP were assessed by a clinical questionnaire, nasal endoscopy and sinusal
      computed tomography. The patients were then medicated with budesonide, 256
      microg/nostril/day, for a 2-month period and afterwards they were submitted to a
      new clinical questionnaire and a new endoscopy. Post-treatment endoscopy revealed
      a significant reduction of polyp size's score (4.25 vs. 2.90, p < 0.01), which
      was associated to improvement of nasal symptoms: posterior rhinorrhea, headache,
      hyposmia, anterior rhinorrhea, and sneezing (p < 0.05). There was also a
      significant improvement of the sum of scores (20.10 vs. 10.30, p < 0.0001).
      Cacosmia and nasal itching did not respond to medical treatment. Patients with a
      higher tomographic extension of the polyp presented a significantly worse
      clinical response (p < 0.05). We conclude that there was partial, but
      significant, improvement of nasal symptoms and polyp size after treatment with
      nasal budesonide and that this clinical improvement was inversely correlated to
      the tomographic extension of NP at diagnosis.

PMID- 17432073
TI  - Lessons learnt in the management of Wegener's Granulomatosis: long-term follow-up
      of 60 patients.
AB  - OBJECTIVE: To assess all patients with Wegener's Granulomatosis treated in
      Nottingham, with particular focus on relapse rate and the useful predictors of
      relapse. We evaluated how well the findings of nasal examination correlated with
      disease relapse compared to other parameters such as c-ANCA, ESR and CRP.
      Presenting features, diagnosis, adverse effects of treatment and mortality rate,
      were also studied. DESIGN: Retrospective examination of 60 patient notes,
      diagnosed and treated for Wegener's granulomatosis at Queen's Medical Centre,
      Nottingham. The mean follow up period was 8.7 years. Relapse was defined as per
      the European Vasculitis Study criteria. RESULTS: cANCA is a useful test at
      presentation for diagnosis but a negative result does not rule out the disease.
      Those presenting with ENT symptoms alone may have less raised inflammatory
      markers but similar cANCA titres as patients with multi-system disease. However,
      at relapse, patients with ENT disease alone have similar levels of inflammatory
      markers as those with multi-system relapse. Nasal examination was useful at
      monitoring the presence of disease activity where the nasal lining is affected.
      CONCLUSIONS: Signs of intranasal disease in the form of granular tissue, erythema
      and bleeding to light touch and crusting over granulation tissue are good
      predictors of disease activity. A raised cANCA, ESR or CRP provide supporting
      information about disease activity but if they are negative this does not exclude
      active disease. cANCA levels were as elevated at relapse in patients who had
      isolated nasal symptoms and signs as in those with evidence of systemic disease.
      Low relapse rates were found possibly due to prompt and rigorous initial
      immunosuppression even in limited disease. This seemed to lead to less
      progression of patients to multi-system disease and hence a low mortality rate of
      5%.

PMID- 17432074
TI  - Optimal time for nasal packing removal after septoplasty. A comparative study.
AB  - OBJECTIVE: The objective of this study was to evaluate the efficacy and
      subjective discomfort of one-day internal dressing compared to that of two-day in
      patients undergoing nasal septal surgery. STUDY DESIGN/METHODS: Prospective,
      randomized, clinical trial conducted on 75 patients undergoing septoplasty in a
      tertiary ENT clinic. Discomfort caused by nasal dressings was evaluated by means
      of a visual analog scale. Postoperative complications were also compared.
      RESULTS: Mean discomfort score for group A (nasal packing for 48 hours) was 3.5
      (SD 1.15) vs. 2.7 (SD 1.52) for group B (nasal packing for 24 hours). Significant
      lower discomfort is reported when the nasal packing is removed the first day
      instead of after two or more days. No increase in complication rate was noticed.
      CONCLUSION: Our results point out that one-day internal nasal dressing is
      preferable to that of two or more days, because of less patient discomfort and
      increased cost-effectiveness without increasing immediate complications.

PMID- 17432075
TI  - Effect of a balanced anaesthetic technique using desflurane and remifentanil on
      surgical conditions during microscopic and endoscopic sinus surgery.
AB  - OBJECTIVES: Controlled hypotension is used to improve surgical conditions during
      microscopic and endoscopic sinus surgery. Several drug combinations are suitable
      to provide deep and predictable level of anaesthesia combined with an exact
      control of intraoperative blood pressure. However, only little is known about the
      relative importance of the level of hypnosis on the one hand and analgesia on the
      other hand. STUDY DESIGN: Prospective, randomized, patient and observer-blinded
      study. METHODS: All 100 consecutive patients received a balanced anaesthesia
      technique using desflurane and remifentanil. Anaesthesia was desflurane
      accentuated with remifentanil-supplementation (DARS-group: 1 MAC desflurane;
      remifentanil: 0.2 microg x kg(-1) x min(-1)) or remifentanil-accentuated with
      desflurane-supplementation (RADS-group: desflurane: 0.5 MAC; remifentanil: 0.4
      microg x kg(-1) x min(-1)). Administration of anaesthetics performed to maintain
      a sufficient level of anaesthesia and to keep mean arterial pressure between 60
      and 70 mmHg (8-9.3 hPa). The attending ENT-surgeons were unaware of the type of
      anaesthesia and rated general surgical conditions and the dryness of the
      operating site on a visual analogue scale (0-10 cm) and on a verbal rating scale
      immediately after surgery. RESULTS: Blood pressure and heart rate was not
      different between the two groups. Dryness of the operating site was rated
      significantly better (p < 0.0001) in the DARS-group (median; 25th/75th
      percentile: 2.0; 1.5-3.5 vs. RADS-group: 2.6; 2.0-4.0) but the overall rating of
      the surgical conditions did not differ between the groups (DARS-group: 2.0; 1.0
      2.4 vs. RADS-group: 2.2; 1.5-3.2). Immediate postoperative recovery times were
      increased in the RADS-group, but there was no difference with respect to fit-for
      discharge criteria one hour after surgery. CONCLUSION: Balanced anaesthesia using
      high dose of desflurane offers small but statistically significant advantages
      with respect to dryness of the operating site compared to an opioid-accentuated
      anaesthesia technique. However, since the opioid-accentuated anaesthetic group
      had a faster immediate recovery both techniques are equally effective for
      microscopic and endoscopic sinus surgery.

PMID- 17432076
TI  - Measuring nasal tip and lobule width; effect of transdomal and lateral crura
      suturing.
AB  - STATEMENT OF PROBLEM: There is no golden standard in measuring the width of the
      nasal tip and lobule. In this study we tried to validate the parameters Tip Index
      (TI) and Lobular Index (LI) as parameters for Nasal Tip Width (NTW) and Nasal
      Lobule Width (NLW) respectively. Trandomal suturing and lateral crura suturing
      were used to alter NTW and NLW respectively. METHODS: Standardized digital
      photographs (basal view) of open approach rhinoplasty patients were analysed.
      Transdomal sutures and lateral crura sutures were used in 29 and 28 patients,
      respectively. TI and LI were determined with digital imaging software (Adobe
      Photoshop) pre- and postoperatively. RESULTS: Average (SD) preoperative LI
      changed from 0.74 (0.07) to 0.71 (0.06) postoperatively with the lateral crura
      suturing technique (p = 0.045). We were not able to measure an effect in TI with
      the transdomal suturing technique. CONCLUSIONS: Detailed postoperative analysis
      with digital imaging software contributes to greater understanding of nasal tip
      mechanics. LI proved to be a valuable technique to describe NLW refinement.

PMID- 17432077
TI  - Nasal fracture reduction: local versus general anaesthesia.
AB  - OBJECTIVE: To investigate the outcomes from nasal fracture reduction performed
      under local anaesthesia (LA) and general anaesthesia (GA). METHOD: A randomised
      multi-centred prospective trial and cohort analysis. Patients were randomised
      into two groups, 74 (53%) underwent closed reduction under LA, 65 (47%) patients
      underwent closed reduction under GA. MAIN OUTCOME MEASURES: Pain scores and
      patient toleration of local or general nasal manipulation was noted. RESULTS: The
      pain score ranged from 0 (no pain) to 10 (unbearable pain). The mean pain score
      in the LA group was 3, compared to 2 in the GA group. LA manipulation was
      tolerated equally well as GA manipulation by 85% of the patients in each group.
      The number of patients requiring a septorhinoplasty was compared between LA 19/74
      (26%), and GA 21/65 (32%). This failed to demonstrate a significant difference
      with a p value of 0.50. The absolute risk difference was 5% with a 95% confidence
      interval of (20% to -10%). CONCLUSION: This trial clearly shows LA to be as
      effective as GA in the first line management of nasal fractures. The degree of
      septal displacement and presence of nasal tip deviation were associated with
      persistent nasal deformity following nasal fracture reduction.

PMID- 17432079
TI  - Rapidly expanding maxillary pneumosinus dilatans.
AB  - Maxillary pneumosinus dilatans is a rare and difficult to diagnose condition at
      its outset. The natural history of a case where a computer tomography (CT) scan
      was performed 6 months prior diagnosis raises the possibity that pneumosisnus
      dilatans and sinus pneumocoele may be a continuum of the same diease process. The
      classification and aetiology are discussed.

PMID- 17432078
TI  - Oncocytic schneiderian papilloma confined to the sphenoid sinus detected by FDG
      PET.
AB  - We report a 55-year-old man with oncocytic schneiderian papilloma confined to the
      sphenoid sinus, which was initially detected by positron emission tomography with
      18F-fluorodeoxyglucose (FDG-PET) at a very early stage. Based on CT and MRI
      findings, we suspected that the tumor was most likely benign; however, positive
      uptake in FDG-PET suggested malignancy. The patient underwent endoscopic
      resection of the tumor, and the histopathological diagnosis turned out to be
      oncocytic schneiderian papilloma. FDG-PET is thought to be a powerful tool to
      search for malignant lesions, but the present case demonstrates the fallibility
      of this technique. This should be taken into consideration when interpreting FDG
      PET images.

PMID- 17432080
TI  - [Hernia surgery in Hungary today--effect of the Lichtenstein-study].
AB  - Based on extensive randomized, multicenter studies, the recent trend in inguinal
      hernia surgery has been towards using a mesh-based tension-free repair, and
      Lichtenstein method is considered to be the procedure of choice. Based on above
      mentioned concern a prospective, multicenter study was conducted. In 15 centers,
      between March of 1999 and 2000, 1434 patients were included in this trial.
      Lichtenstein hernia repair was associated with less postoperative pain, lower
      complications rate,faster recovery, and lower recurrence rate compared with
      suture repair made under tension. Both the attitude and practice has been changed
      thoroughly in Hungary and the Bassini repair seems to be replaced by the
      Lichtenstein procedure. Mesh implantation increased from 1% (1998) to 34% (2005).
      The study has largely contributed to the national spread of this operation and
      has doubtlessly verified the advantage of data processing through the internet.

PMID- 17432081
TI  - [Fenotypical diversity of hereditary non-polyposis colorectal carcinoma. Pedigree
      and genetical analysis of two mutation carrier patients].
AB  - INTRODUCTION: The phenotype of HNPCC shows great diversity. Investigation of the
      disease needs the application of both the Amsterdam and Bethesda Guidelines. The
      clinical diagnosis of HNPCC can be established by means of thorough family
      history containing more generations. The immunohistochemistry and MSI
      investigation of the tumorous tissue as well as the detection of mutations based
      on DNA sequencing could reinforce the existence of the possible hereditary
      tendency. PATIENTS AND METHODS: Two pedigrees were selected based on the above
      mentioned protocol at the Surgical Institute of the University of Debrecen,
      Medical and Health Science Center. Amongst first-degree relatives of the 31-year
      old male patient suffering from colorectal carcinoma (1st patient), three other
      colorectal, one gastric, one breast and one lung tumors have been found. Two
      genetic alterations of hMSH2 gene were detected in this family, which were also
      detectable in other family members. The mutation of exon 7 was not at that time
      available in international databases, so it was detected by us for the first
      time. We were able to find alterations of both hMLH1 and hMSH2 genes in the case
      of the 25-year old patient with synchronous colorectal carcinomas (2nd patient).
      These alterations could be detected in other family members as well. The whole
      pedigree contains only one other case of colorectal carcinoma besides the index
      person. CONCLUSION: Several HNPCC families would be missed in case of considering
      the Amsterdam Criteria alone. The application of the Bethesda Guidelines is
      absolutely necessary for the detection of families with poor history at the first
      screening. The association of a polymorphism and a pathogen mutation in one
      person could lead to early onset of colorectal carcinoma.

PMID- 17432082
TI  - [Role of autologous antebrachial arteriovenous fistula for vascular access in
      hemodialysis].
AB  - Numbers of arteriovenous (AV) fistula creation increase worldwide. Hemodialysis
      is more effective, patients live longer, they need more access operation. The
      optimal strategy for the order and sequence of the different type and
      localization of AV fistulas remains obscure. Based on internationally acclaimed
      guidelines, autogenous access should be performed whenever possible and the first
      operation of choice is the radio-cephalic fistula at the wrist, the second type
      is the elbow fistula. The area between the standard exposures means also good
      access area and its usage is not emphasized properly. At our department the
      performance of autogenous fistulas have always been favoured. Beside the wrist
      radio-cephalic and elbow fistulas a significant number of autologous forearm AV
      fistulas has been operated. Our aim was to study the short and long term results
      of the autogenous forearm fistulas at atypical anatomic positions. We also
      examined whether the patency rate is affected by different variables as diabetes
      mellitus, acute or chronic operative situation, the indication of surgery, the
      quality of thrill at the end of shunt creation, the diameter and quality of the
      vein. Between 1997 and 2005 we performed 1018 AV shunts in an academic tertiary
      care center. 97 autologous antebrachial AV shunts were performed. The average
      follow up time was 31.3 months. The primary patency rate was 97%, 92% and 63% at
      the end of the first, second and sixth years, respectively. The patency rate was
      not significantly affected by any of the examined variables mentioned above. The
      patency rate of the autologous antebrachial AV shunt is comparable to the wrist
      and elbow fistulas, so our results support the practice of performing fistula at
      this atypical localization. More proximal autologous fistulas and prosthetic
      graft implantation could be postponed, this way valuable time could be saved for
      the uremic patients.

PMID- 17432083
TI  - [Effects of phosphatidylcholine therapy after hindlimb ischemia and reperfusion].
AB  - BACKGROUND: Microcirculatory dysfunctions and mast cell reactions play important
      roles in hypoxic tissue injuries. The aims of this study were to characterize the
      effects of hindlimb ischemia-reperfusion on the periosteal microcirculation and
      to define the consequences of systemic phosphatidylcholine therapy during this
      condition. MATERIALS AND METHODS: Microcirculatory changes were visualized by
      means of fluorescence intravital videomicroscopy in anesthetized Wistar rats. 60
      min of complete hindlimb ischemia was followed by a 180-min reperfusion in the
      presence of phosphatidylcholine treatment (50 mg/kg iv; in the second 10 min of
      reperfusion) or vehicle. Further two groups served as vehicle- or PC-treated sham
      operated controls. The proportion of degranulated mast cells and the leukocyte
      accumulation (myeloperoxidase, MPO assay) were determined in muscle biopsies.
      RESULTS: Ischemia-reperfusion significantly increased the muscle MPO activity
      (from 14.94 to 63.45 mU/mg) and the proportion of degranulated mast cells (to
      82.5%). The periosteal capillary red blood cell velocity (RBCV) and the
      functional capillary density (FCD) had decreased, while the primary and secondary
      leukocyte-endothelial cell interactions had increased by the end of reperfusion
      (rolling from 20.8 to 40.0%, and firm adherence from 254 to 872 mm-2).
      Phosphatidylcholine treatment decreased the leukocyte rolling and sticking,
      preserved the FCD and improved the RBCV The mast cell degranulation and MPO
      activity diminished significantly in the muscle layer. CONCLUSIONS: Mast cell
      degranulation accompanies ischemia-reperfusion-induced periosteal
      microcirculatory derangement. Systemic phosphatidylcholine treatment affords
      protection through ameliorating secondary inflammatory reactions.

PMID- 17432084
TI  - [Esophagus replacement with anisoperistaltic left colon after removal of skin
      tube cancer].
AB  - Authors replaced the esophagus with anisoperistaltic left colon because they had
      no other possibilities. In this case twenty-one years ago after an esophageal
      injury the patient underwent gastric resection, removal of the esophagus and
      replacement with a skin tube created from a myocutaneous flap. Unfortunately the
      right colon earlier had been removed after an unsuccessful replacement. Twenty
      one years later carcinoma developed in the skin tube therefore the tumour was
      removed and anisoperistaltic left colon was used as a "new esophagus". The pulled
      up left colon was supplied by the left colic artery and supercharged by a
      vascular anastomosis on the neck. Authors would like to present that esophageal
      replacement with anisoperistaltic left colon is a feasible method if no other
      therapeutic option remains.

PMID- 17432085
TI  - [Leiomyosarcoma of the oesophagus: a case report].
AB  - Authors treated a oesophageal sarcoma in a 46 year old female patient in July
      1999. The tumor caused retrosternal pain and weight loss but did not disturb
      swallowing. After resecting the tumor, an intrathoracic oesophago-gastrostomy was
      performed. On the 18th postoperative day the patient went home without any
      complaints. Histologically the tumor proved to be a leiomyosarcoma. The patient
      has had no complaints in the past 6 years. On account of this case report the
      authors review the literature on this rare disease.

PMID- 17432086
TI  - [Complete regression after neoadjuvant chemotherapy in locally advanced gastric
      cancer causing peritonitis carcinomatosa--a case report].
AB  - Gastric cancer is one of the most frequent cause of mortality, survival data are
      insufficient. Several chemotherapeutic combinations were applied successfully in
      advanced gastric cancer, following total tumor regression and radical resection,
      but there are very few cases with total regression after a disease forming
      carcinosis and causing ascites. In our report, a middle age patient suffering
      from locally advanced gastric cancer with peritonitis carcinomatosa and ascites
      was treated with neoadjuvant chemotherapy (DCF: docetaxel, cisplatin,
      fluorouracil protocol) successfully, as at the restaging examination total tumor
      regression was found. Ascites and carcinosis disappeared, so we performed radical
      distal surgical resection. The histological preparation resulted in 100% tumor
      regression of the specimen. Postoperatively the patient was given adjuvant DCF
      chemotherapy. The therapeutic modality of cases with advanced gastric cancer,
      especially with carcinosis must be reassessed, because according to our and some
      international reports, these patients are also candidates for effective
      neoadjuvant therapy and curative resection. In our own and in the experience of
      some others the combinations with taxanes and its derivatives are one of the most
      effective.

PMID- 17432087
TI  - [Laparoscopic choledocho-duodenostomy].
AB  - It is widely accepted today, that laparoscopic exploration of the common bile
      duct is an effective method for the treatment of obstructive jaundice, when it is
      caused by ductal calculi. In case of periampullary lesions, endoscopic stenting
      or surgical biliodigestive diversion might be the treatment of choice when
      radical solution is impossible or not necessary. The latter is still performed by
      laparotomy in a large number of cases due to technical challenges of the
      biliodigestive anastomosis in the laparoscopic approach. The authors present the
      case of a 76 year old patient with poor general condition, obstructive jaundice
      and signs of biliary calculosis by ultrasound. Attempt to its endoscopic
      verification and treatment has failed, due to lack of cooperation. Laparoscopic
      common bile duct exploration was performed which has revealed small ductal
      calculi and stricture of the papilla. After extraction of ductal calculi, hand
      sutured, side to side choledocho-duodenostomy was performed laparoscopically to
      achieve permanent biliary diversion. The anastomosis was prepared with
      absorbable, monolayer, interrupted sutures. The postoperative course was
      uneventful During regular follow up no complications have been observed. The
      authors conclude, that in selected cases, choledocho-duodenostomy might be
      constructed safely laparoscopically, too. This procedure is especially
      advantageous for elderly patients and for patients in poor condition.

PMID- 17432088
TI  - [The role of the antiepileptic drugs at the development of the sexual
      dysfunctions in male epileptic patients].
AB  - It is well known that alterations in sexual functions occur more frequently in
      men with epilepsy than in general population. The results of the epidemiological
      studies are considerably diverge from one another (3-61%), so the exact value of
      the incidence is not known. The most common form of sexual dysfunctions is the
      hyposexuality, determined as a overall reduction in sexual interest, awareness,
      and activity. Sexual dysfunction, as a disorder is often multifactorial, but the
      role of medical factors can be the most important in the development. The
      endocrinological disturbances occurring in epilepsy are mainly caused by the
      pharmacokinetic interactions among the antiepileptic medication. The enzyme
      inductor drugs decrease the level of free testosterone, dihydrotestosterone,
      follicle stimulating hormone, and luteinizing hormone, and increase the sex
      hormone-binding globulin and estradiol levels. In valproate treated men
      significantly lower follicle stimulating hormone and luteinizing hormone
      concentrations, and free/total carnitine ratio, and higher dehydroepiandrosterone
      concentration can be detected. The enzyme inductor antiepileptic drugs can
      decrease the biologically active testosterone level by stimulating the aromatase
      and the hepatic cytochrome P450 enzymes, which can result in the development of
      sexual dysfunctions. Hormonal changes resulting in the alteration of the androgen
      synthesis and gonadotropin levels may contribute to the sexual dysfunction
      observed in valproate treated epileptic patients. If the role of the
      antiepileptic medication can be proven in the development of the sexual
      dysfunctions, changing in the antiepileptic drug therapy is recommended.
      According to evidences, the usage of oxcarbazepine and lamotrigine is not
      associated with changes in hormonal levels, and does not lead to alterations in
      sexual functions. In case of sexual dysfunctions switching from carbamazepine to
      oxcarbazepine, levetiracetam, or gabapentin is recommended in patients with
      partial epilepsy, and from valproate to lamotrigine or levetiracetam in patients
      with idiopathic generalized epilepsy. Enforcement of the primary prevention in
      the treatment of men with epilepsy is an important task of the future.

PMID- 17432089
TI  - [Pramipexole therapy of restless legs syndrome].
AB  - The restless legs syndrome is a disorder belonging to the family of movement
      disorders during sleep, often remains unrecognized, although it is the second
      most common cause of chronic sleep deficiency and daytime sleepiness. In
      accordance with international guidelines, pharmacotherapy of this disorder should
      begin with a dopamine agonist. Owing to their efficacy and favorable safety
      profile, newly introduced, selective dopamine agonists have become extensively
      used for this purpose. This study evaluated the efficacy of one of the products
      in this group, pramipexole. Fifty-one patients suffering from idiopathic restless
      legs syndrome underwent monotherapy with pramipexole in daily doses of 0.25 to
      1.0 mg. Therapeutic efficacy was evaluated using three tools, i.e. follow-up
      questionnaires, actigraphy, and Forced Immobilisation Test. An excellent
      therapeutic effect was seen in more than 80 per cent of the study population. As
      shown by findings of the follow-up questionnaires, pramipexole resulted in
      substantial improvements of both daytime and nighttime symptoms of RLS.
      Actigraphy monitoring demonstrated a statistically significant increase in the
      ratio of time spent without limb movement to the time spent in bed; furthermore,
      the result of the Forced Immobilisation Test also improved. It seems fair to
      conclude from the findings of this study that pramipexole monotherapy is an
      effective treatment in restless legs syndrome.

PMID- 17432090
TI  - [The familial incidence of epilepsy in the group of epileptic patients examined
      after their first seizure--pilot study].
AB  - INTRODUCTION: It is essential to identify the genetic factors of epilepsy in the
      every day clinical practice for several reasons. The proof of the genetically
      defined sub-clusters existing inside the epileptic disease group is significant
      in diagnoses and therapy. The risk of inheriting epilepsy could influence the
      patient's family planning which has a great impact on their quality of life. THE
      AIM OF THE STUDY: To analyse clinical data obtained from patients examined after
      their first provoked or unprovoked seizure and the observation of the recurrence
      of seizures. To compare the data obtained with the familial occurrence of
      epilepsy. POPULATION AND METHODS: Data was obtained from a questionnaire
      developed by the authors. The epileptic patients with positive familial data
      underwent to an analysis of their family tree. RESULTS: Of 120 persons who were
      examined the prevalence of epilepsy in their family was 20.4%. This corresponds
      to the familial prevalence of generalised epilepsy according to the published
      clinical data. The recurrence of seizures was experienced by 32% of the patients
      with a family background affected by epilepsy. The risk of recurring seizures was
      the highest if the familial epilepsy manifested itself in the same generation
      (among brothers or sisters) and if we were able to register epileptiform activity
      on the interictal EEG. According to our clinical data the genetic set up can play
      a role also in the provoked first epileptic seizure. The incidence of familial
      epilepsy was found high (12.72%) in the presence of incidental epileptic seizures
      when the EEG was free of epileptiform alterations. CONCLUSION: 1. The genetic
      basis for the first epileptic seizure in the population of young adults
      approaches the data known in idiopathic generalised epilepsy irrespective of the
      fact whether it was related to the seizure provoking factors or not. 2. The risk
      of seizure reactivation was higher in non-provoked seizures then at .the
      incidental epileptic symptoms. Seizure reactivation had to be taken into
      consideration when epileptiform patterns appeared on the patient's EEG and/or
      epileptic symptoms were experienced by the patient's brother or sister. The
      probability of recurring seizures was lower if the epileptic seizures manifested
      in parents or earlier generations.

PMID- 17432091
TI  - [Clinical experience with levetiracetam for adults with epilepsy].
AB  - OBJECTIVE: A retrospective study to evaluate the efficacy of levetiracetam in the
      treatment of adult pharmacoresistant epilepsy. METHOD: Retrospective work up of
      our treatment-experiences with 55 pharmacoresistant patients treated with
      levetiracetam (11 of them on monotherapy) for 6-39 months. Three treatment groups
      were analysed: idiopathic generalised epilepsy (9 patients); partial epilepsy (30
      patients); malignant or malignated epileptic syndromes (16 patients). RESULT:
      Seven idiopathic generalised patients (77%) and 5 partial epilepsy patients (16%)
      became seizure free. One idiopathic generalised epileptic patient, 10 partial
      epilepsy patients (33%) significantly improved. Six patients (37%) from the group
      of malignant or malignated epileptic syndromes also significantly improved. Five
      of the improved idiopathic generalised epilepsy patients and 6 of the improved
      partial epilepsy patients received levetiracetam monotherapy. Altogether seven
      patients (12% of the whole population) relapsed after a 4-15 months improved
      period. Fifteen patients (27%) suffered side effects (mainly somnolence,
      headache, dizziness and irritability) improving after dose reduction of
      levetiracetam (generally below 2000 mg pro day). CONCLUSION: Levetiracetam is an
      effective, well tolerable, broad-spectrum drug as adjunctive treatment or
      monotherapy in adult patients unsuccessfully treated with other antiepileptic
      drugs.

PMID- 17432092
TI  - [Application of functional MR-images acquired at low field in planning of
      neurosurgical operation close to an eloquent brain area].
AB  - AIM OF THE STUDY: Presentation of functional MRI performed at low magnetic field
      (1 Tesla) for planning microsurgical operation in a patient suffering from tumor
      close to an eloquent brain area. METHODS: Microsurgical removal navigated by
      frameless stereotaxy of an intrinsic tumor located in eloquent area is indicated
      if speech function is not damaged, i.e. exact localisation and relationship of
      the tumor and speech area can be defined. Before operation an optimized EPI based
      2D sequence was applied to yield functional MR images. At the planning of the
      operation the paradigm used for the localization of the sensory language cortex
      contained passive listening to a text. Control investigations were performed one
      month postoperatively. A specific psychological test, as an additional
      investigation to estimate the accurate level of the sensory language function,
      was also conducted. RESULTS: Low resolution (matrix of 64x 64) functional MR
      images visualized sensory speech center and auditory cortex satisfactorily. The
      scans showed clearly that the Wernicke's region was situated just above the tumor
      (WHO grade II glioma), and this finding increased the safety of intraoperative
      localization and reduced the risk of morbidity. Control examinations revealed
      minimal decrease in sensory language function, however, it was not noticeable for
      either the patient or her surroundings. CONCLUSION: Optimized functional MR
      imaging performed at low magnetic field can support planning of neurosurgical
      operations and reduce the morbidity of microsurgical interventions.

PMID- 17432093
TI  - [Nonsense mutation 193C>T of neurofibromatosis type 2--a neurosurgical
      challenge].
AB  - A 15 years old male was operated because of incidentally found intercostal
      schwannoma. Two years later severe cerebellar ataxia and left sided anacusis
      developed. MRI revealed bilateral vestibularis tumors and multiple cervical
      intradural extramedullary myelin compressing lesions. After partial resection of
      the huge left sided cerebello-pontine tumor, histologically schwannoma, and the
      extirpation of the multiple cervical meningiomas the patient died three months
      later due to septic complications. The 24 years old mother had been operated on
      similar lesions 12 years earlier, after two weeks postoperative period she died.
      Her 14 years old twins are living, a boy also with bilateral acoustic tumours and
      a girl who is intact. Genetic investigation revealed C>T nonsense mutation at
      position 193 in the exon 2 of the NF2 gene. This mutation cause premature
      truncation of the gene protein and is probably in connection with the clinically
      severe phenotype. Early diagnosis of this type of neurofibromatosis is mandatory
      concerning the therapy.

PMID- 17432094
TI  - [Uncommon manifestation of central nervous system sarcoidosis].
AB  - Two cases of uncommon manifestation of central nervous system sarcoidosis are
      reported. A 42 year-old man had a spinal cord sarcoidosis. MRI of the spinal cord
      showed myelopathy in the cervico-thoracic region, and the T2-weighted image
      showed increasing signal intensity. Neurological symptoms did not correlate with
      radiological abnormalities. Neurological manifestation was paucisymptomatic. Half
      a year later steroid and azathioprine therapy led to almost complete radiological
      and clinical regression. In the second case we present a 49 year-old woman who
      had left side internuclear ophthalmoplegia and the brainstem lesion. The patient
      was proven to have sarcoidosis. In this case no abnormalities were found in brain
      MRI. Neurological symptoms could not be detected by MRI, probably caused by
      brainstem parenchymal lesions consisting of microgranulomatosis that is sarcoid
      "brainstem encephalitis". Neurological symptoms improved after steroid treatment
      in this case too. In both of the cases pulmonary lymphadenopathy helped to
      diagnose sarcoidosis. In our cases there were interesting correlations between
      neurological symptoms and MRI abnormalities. At the spinal cord sarcoidosis the
      radiological abnormalities were more striking than the clinical manifestation. In
      the other case we found distinct brainstem symptoms but could not detect MRI
      abnormalities.

PMID- 17432095
TI  - [Hereditary motor and sensory Lom-neuropathy--first Hungarian case report].
AB  - Hereditary motor and sensory neuropathy-Lom is an autosomal recessive disorder of
      the peripheral nervous system, which occurs only in the european Roma population.
      The symptoms start in the first decade with slowly progressive gait disturbance,
      weakness and wasting of distal upper extremity muscles, joint deformities and
      hearing loss develop later in the second and third decades. This disorder is
      caused by a homozygous missense mutation of the NDRG1 gene, located in the 8q24
      region. The Schwann cell dysfunction is most probably caused by altered lipid
      metabolism as a consequence of the NDRG1 mutation. Molecular genetic testing can
      be a first diagnostic step among roma individuals showing a Lom neuropathy
      phenotype, making evaluation of such patients and also genetic counselling faster
      and easier. Screening for hereditary neuromuscular disorders in this genetically
      isolated community may become an important public health issue in the near
      future.

PMID- 17432096
TI  - A case of schizencephaly with polymicrogyria.
AB  - A case of extensive bilateral frontotemporal schizencephaly is alleged - more
      extensively in the left hemisphere - which associated with polymicrogyria. The
      cortical anomaly was discovered only incidentally by MR examination in a 22 year
      old man who suffered from headache due to a mild head trauma. Neurological
      examination proved to be negative. He had no complaints or symptoms a few weeks
      later. The developmental anomalies in corticalisation are shortly overviewed in
      this group together with the possible causing factors. It has been emphasized the
      importance of the precise intrauterine and/or postpartum differential diagnosis
      between schizencephaly, porencephaly and other failure in corticalisation.

PMID- 17432097
TI  - [Updates in practical neurology--I. The principles of modern levodopa therapy in
      Parkinson's disease].
AB  - Despite the levodopa is used for the treatment of Parkinson's disease for a long
      time, recently many questions raised about its clinical use. New issues emerged
      based on the clinical trials, on latest neuroimaging data and on better
      understanding the pathomechanism of motor complications. These observations have
      changed the routine clinical use of levodopa. In this review we summarize the
      evidences and practical implications of levodopa therapy.

PMID- 17432098
TI  - [Some additional thoughts on sudden/unexpected death (SUDEP) in epilepsy].

PMID- 17432099
TI  - The role of non-corticosteroid related factors in osteonecrosis (ON) in systemic
      lupus erythematosus: a nested case-control study of inception patients.
AB  - Several factors have been associated with the development of osteonecrosis (ON)
      in SLE but corticosteroid (CS) therapy has been the most consistent association.
      We sought to determine factors that predisposed to, or protected from, the
      development of ON in lupus patients when cumulative oral corticosteroid doses
      were matched between cases and controls, thereby removing presence of
      corticosteroid therapy and cumulative dose as risk factors. A nested case-control
      study of an inception cohort of SLE patients was used to determine the clinical,
      laboratory and therapeutic differences between patients who developed their first
      ON event and patients who did not develop ON, having matched these groups for
      their cumulative oral corticosteroid doses. Of the 570 patients seen within the
      first year after diagnosis 65 (11.4%) developed ON. None of the variables
      examined were found to confer additional ON risk in multivariate analysis. It
      appears that the major factor associated with the development of ON is
      corticosteroid therapy. Factors which may protect a majority of patients on
      corticosteroids from developing ON remain to be elucidated.

PMID- 17432100
TI  - Cutaneous lesions of the digits in systemic lupus erythematosus: 50 cases.
AB  - The objective of this study was to observe the clinical and pathologic features
      of digital lesions in a cohort of 50 patients with systemic lupus erythematosus
      (SLE). Biopsy and pictures of digital lesions were performed in 50 consecutive
      patients with SLE and digital lesions. A clinical diagnosis of vasculitis was
      previously suggested in 36% of cases. Pictures were reviewed by three
      dermatologists and all the tissue sections were analysed by the same pathologist.
      Files of patients were reviewed retrospectively. Activity of SLE was established
      according to the lupus activity index (LAI). Digital lesions in SLE were
      frequently painful (60%) with a finger-pulp inflammation (70%). According to
      clinical and pathological correlation, five patients had acute cutaneous lupus,
      five subacute cutaneous lupus, 21 discoid lupus and 15 chilblain lupus. Two
      patients presented vasculitis: one had an urticarial vasculitis concomitantly to
      a lupus flare, the other had an erythema elevatum diutinum, independent of SLE
      evolution. Thrombosis of dermal vessels was present in two patients with SLE
      associated antiphospholipid syndrome and in two patients with chilblain lupus.
      LAI was >1.5 in only seven patients. These results highlight the tendency to
      clinically overestimate the prevalence of cutaneous vasculitis of the fingers in
      patients without active SLE. Clinical features of cutaneous lupus of the digits
      are polymorphous. So, a pathological examination of the lesions is often
      necessary for diagnosis and proper management.

PMID- 17432101
TI  - Association of Epstein-Barr virus infection with systemic lupus erythematosus in
      Taiwan.
AB  - An association between Epstein-Barr virus (EBV) infection and systemic lupus
      erythematosus (SLE) has been suggested from previous serologic evidence. Since
      most adults in Taiwan are EBV-infected, seroepidemiologic studies based on
      standard assays for EBV are unlikely to dissociate SLE patients and control
      groups. We reexamine this question by using novel methodologies in which IgA anti
      EBV-coded nuclear antigens-1 (EBNA-1) and IgG anti-EBV DNase antibodies were
      analysed by ELISA, and EBV viral loads were detected by real-time quantitative
      PCR for 93 adult SLE patients and 370 age-, sex- and living place-matched healthy
      controls in Taiwan. The specificities of antibodies for extractible nuclear
      antigens were determined by Western blot. Our results show that IgA anti-EBV
      EBNA1 antibodies were detectable in 31.2% SLE patients but only in 4.1% of
      controls (odds ratio [OR] = 10.72, 95% confidence interval [CI] = 5.19-22.35; P <
      10(-7)), IgG anti-EBV DNase antibodies were detected in 53.8% SLE patients but
      only in 12.2% controls (OR = 8.40, 95% CI = 4.87-14.51; P < 10(-7)). EBV DNA was
      amplifiable from the sera of 41.9% SLE patients but from only 3.24% controls (P <
      0.05). A significant association of IgG anti-EBV DNase antibodies with anti
      Sm/RNP antibodies was observed (P < 0.005). The higher seroreactivity and higher
      copy numbers of EBV genome indicated association of EBV infection with SLE in
      Taiwan.

PMID- 17432102
TI  - Clusters of disease manifestations in patients with antiphospholipid syndrome
      demonstrated by factor analysis.
AB  - The antiphospholipid syndrome (APS) is now recognized as a multi-system disease,
      the clinical expression of which may include various target-organs involvements.
      Despite the reported heterogeneity in clinical presentation of APS, the
      interrelations between various manifestations of the disease has not yet been
      studied. We evaluated the principle associations between a variety of clinical
      manifestations in APS patients, applying factor analysis. Two-hundred and forty
      six APS patients were studied. The following disease manifestations were used for
      the factor analysis: recurrent fetal loss, intrauterine growth restriction
      (IUGR), venous and arterial thrombosis, cardiac valves thickening/dysfunction,
      valvular vegetations, stroke, epilepsy, migraine, arthritis, livedo reticularis,
      thrombocytopenia, leukopenia and autoimmune hemolytic anemia (AIHA). The results
      were further analysed in relation to sex and to primary APS versus APS associated
      with SLE. Five factors were derived, which accounted for 59.7% of the variance of
      the matrix. Factor 1 (which explained 18.5% of variance of the original matrix)
      represented the association between cardiac valves abnormalities, livedo
      reticularis and AIHA. Factor 2 (13.8% of variance) represented association
      between arthritis, thrombocytopenia and leukopenia. Factor 3 (10.3% of variance)
      represented an association between recurrent fetal loss and IUGR. Factor 4 (9.3%
      of variance) represented inverse correlation between arterial and venous
      thrombosis. Factor 5 (7.8% of variance) represented an association between
      epilepsy and migraine. Application of factor analysis revealed specific clusters
      of cardiac, cutaneous, hematological and neurological manifestations. Our result
      also point to a possible divergence of arterial and venous thrombotic tendency.
      Awareness of these patterns might give us a better understanding of the disease.

PMID- 17432103
TI  - Cardiovascular autonomic dysfunction in systemic lupus, rheumatoid arthritis,
      primary Sjogren syndrome and other autoimmune diseases.
AB  - Neurological manifestations are known to occur in patients with autoimmune
      diseases, often subclinically, but autonomic nervous system (ANS) involvement has
      rarely been studied, and studies have shown conflicting results. We performed
      cardiovascular ANS assessment in 125 patients with autoimmune diseases in this
      case-control study, including 54 patients with systemic lupus erythematosus
      (SLE), 39 with rheumatoid arthritis (RA), 20 with primary Sjbgren syndrome (pSS),
      eight patients with polymyalgia rheumatica (PR), four patients with scleroderma
      (Ssc) and 35 healthy control subjects. The control group was formed to
      approximately match the mean age of SLE, RA and pSS patients; controls did not
      differ significantly by gender from the autoimmune pations. All patients with
      were in stable condition. Autonomic nervous system dysfunction was diagnosed by
      applying cardiovascular reflex tests according to Ewing, and was considered to
      exist if at least two tests were positive. Vagal dysfunction was established by
      applying three tests: Valsalva manoeuvre, deep breathing test, and heart rate
      response to standing. Sympathetic dysfunction was examined by applying two tests:
      blood pressure response to standing and handgrip test. In all cardiovascular
      reflex tests, frequencies of abnormal results were significantly higher among the
      patients than among the controls (P < 0.05). The difference between the
      autoimmune patients and the controls was particularly significant in sympathetic
      and parasympathetic tests, with P < 0.0001. No correlation was found between
      disease duration, clinical manifestations, cardiovascular risk factors and
      diseases activity on the one hand, and ANS dysfunction on the other hand.
      Cardiovascular autonomic dysfunction was revealed in the majority of autoimmune
      patients.

PMID- 17432104
TI  - Sm antibodies increase risk of death in systemic lupus erythematosus.
AB  - The importance of ethnicity, socioeconomic status (SES), and autoantibodies as
      prognostic indicators in lupus were evaluated in a Canadian cohort. A
      retrospective review of 330 lupus patients identified demographic features
      including age and self reported ethnicity, SES, lupus features, antibodies to
      extractable nuclear antigens (ENAs), organ damage (SDI score), and mortality. ENA
      (Sm, RNP, Ro, La) associations with lupus features, predictors of final visit SDI
      score and the contributions of ethnicity, autoantibodies and SES on overall
      mortality were determined. Three ethnic groups [Caucasians (C), Asian-Orientals
      (AO), Native American First Nations (FN)] differed in disease severity and SES.
      FN and AO patients had similarly severe lupus, developing lupus at an earlier
      age, with more renal and neurological involvement, greater SDI scores at last
      visit, and more frequently had Sm or RNP antibodies than C. FN had the highest
      mortality and lowest SES. Sm and RNP antibodies were associated with renal and
      neurologic involvement. RNP, education and duration of follow-up predicted SDI
      score. Sm increased risk of death. In conclusion, RNP and lower SES are
      associated with lupus related organ damage and the presence of Sm is a predictor
      of mortality in lupus, independent of ethnicity, renal involvement or
      socioeconomic status.

PMID- 17432105
TI  - Oxidative stress in systemic lupus erythematosus: relationship to disease
      activity and symptoms.
AB  - Oxidative stress may play a role in the pathogenesis of systemic lupus
      erythematosus (SLE). We examined the hypothesis that oxidative stress was
      associated with indices of lupus disease activity and severity of symptoms.
      Urinary F2 isoprostane excretion, a validated marker of oxidative stress, was
      measured in 95 patients with SLE and 103 healthy controls. Outcome measures
      included SLEDAI and SLICC scores, the modified health assessment questionnaire,
      the fatigue severity scale (FSS), and visual analogue scales (VAS) for fatigue,
      pain and overall disease activity. F2 isoprostane excretion was compared in
      patients and controls, and its relationship with clinical variables in SLE
      examined. F2 isoprostane excretion did not differ significantly among patients
      with lupus (2.7 +/- 2.3 ng/mg Cr) and control subjects (2.2 +/- 1.4 ng/mg Cr) (P
      = 0.70). In patients with lupus, F2 isoprostane concentrations were independently
      associated with higher patient reported disease activity (VAS) (OR = 1.52, P =
      0.01), fatigue (FSS, OR = 1.52, P = 0.03) and lower quality of life (OR = 0.73, P
      = 0.05), but not with objective markers or inflammation or disease activity. In
      conclusion, F2 isoprostane excretion is associated with patient-reported symptoms
      in SLE but not with measures of inflammation, SLEDAI or SLICC. Oxidative stress
      may contribute to debilitating symptoms such as fatigue in SLE.

PMID- 17432106
TI  - Acute granulomatous lupus pneumonitis: the first case report.
AB  - Acute lupus pneumonitis is a rare form of pulmonary involvement in systemic lupus
      erythematosus (SLE). We present herein a patient with acute lupus pneumonitis who
      presented with acute onset of fever, cough, dyspnea and a miliary pattern on
      chest radiographs and computer tomography. Lung histopathology revealed
      bronchocentric granulomatosis. To our knowledge, this is the first documented
      case of granulomas in lung parenchyma believed to be caused by SLE. The
      differential diagnoses of acute lupus pneumonitis and the pertinent literature
      are discussed.

PMID- 17432107
TI  - Unique hepatic imaging features in a patient with nodular regenerative
      hyperplasia of the liver associating with systemic lupus erythematosus.
AB  - Nodular regenerative hyperplasia (NRH) of the liver, characterized by
      regenerative nodules distributed throughout the liver in the absence of fibrosis,
      is a rare but important complication of systemic lupus erythematosus (SLE). The
      main consequence of NRH is non-cirrhotic portal hypertension. We describe a
      female patient who had immune thrombocytopenia in association with elevated liver
      enzymes and evidence of portal hypertension as initial manifestations of SLE.
      Computed tomographic scan and magnetic resonance imaging of the liver in this
      patient showed enhancing periportal tubular structures distributed throughout the
      liver. The diagnosis of NRH was eventually disclosed by transcutaneous needle
      liver biopsy. The pattern of radiological abnormality in this patient has not
      been described previously in NRH. In addition, we believe this is a first
      reported case of SLE presenting with immune thrombocytopenia in association with
      NRH.

PMID- 17432108
TI  - Lupus nephritis: assessing the evidence, considering the future.

PMID- 17432109
TI  - Thirty years of cyclophosphamide: assessing the evidence.
AB  - The ideal therapy for lupus nephritis should reduce mortality and end-stage renal
      disease in the long term, induce early response and remission, prevent flares,
      have minimal side-effects and not compromise fertility. It should also be active
      in all ethnic groups, widely available and cost effective. Despite 30 years'
      clinical experience, the ability of cyclophosphamide to meet these needs is not
      supported by robust evidence. The first National Institutes for Health (NIH)
      trial in 1986 led to a shift from oral to intravenous cyclophosphamide. The three
      NIH trials together then led to the dogma that high-dose intravenous
      cyclophosphamide is the only cytotoxic agent superior to steroids alone in lupus
      nephritis and to its general acceptance as the 'standard of care'. Since then,
      high-dose intravenous cyclophosphamide has been shown to have no impact on
      survival, to be less effective in black patients and to have many side-effects,
      particularly an unacceptable risk of premature menopause. The Euro-Lupus
      Nephritis Trial found that low-dose intravenous cyclophosphamide could be used as
      an alternative to a high-dose regimen and was associated with half as many severe
      infections. Other advantages include no hospitalisation and virtually no risk of
      premature gonadal failure. Other studies have looked at regimens in which
      cyclophosphamide is entirely replaced--for example, with mycophenolate mofetil-
      and have found fewer side-effects and better induction of remission. Intravenous
      cyclophosphamide is the only therapy with long-term data for reduction of end
      stage renal disease. As data on other therapies accumulate, however, intravenous
      cyclophosphamide might no longer be considered the standard treatment for lupus
      nephritis.

PMID- 17432110
TI  - Current management of lupus nephritis: popular misconceptions.
AB  - The management of lupus nephritis is typified by popular misconceptions: that
      there is a 'standard of care', that treatment has well-defined aims and that the
      optimum length of treatment is established. In reality, however, uncertainties
      still exist and the evidence base remains weak. Until recently, initial therapy
      for class IV lupus nephritis typically involved intravenous cyclophosphamide, yet
      although cyclophosphamide is superior to azathioprine in improving renal
      function, it is not superior in terms of mortality. In fact, recent studies show
      mycophenolate mofetil to be superior to cyclophosphamide in terms of response
      rate and safety profile and at least as effective as other immunosuppressants.
      The role of steroids is unclear. Clearly, no standard of care exists in lupus
      nephritis. The Euro-Lupus Nephritis Trial found that treatment response at six
      months, in terms of reduced serum creatinine and proteinuria, was the best
      predictor of long-term renal outcome. Proteinuria, however, can take a long time
      to reach baseline levels, and normalization of urine is not the same as loss of
      histological disease activity. Response to treatment thus is not the same as
      disease remission. Although treatment should aim to reduce the risk of end-stage
      renal disease and death, control of proteinuria and prevention of flares are also
      important. Patients who have nephritic flares are almost seven times as likely to
      progress to end-stage renal disease compared with those who do not. Regimens
      involving maintenance phases have been developed, but uncertainty remains about
      the risk of flares and how they can be predicted. The optimum duration of
      treatment has yet to be determined.

PMID- 17432111
TI  - Exploring new territory: considering the future.
AB  - The European League Against Rheumatism (EULAR)'s guidelines for lupus state that
      mycophenolate mofetil has at least equivalent efficacy to and less toxicity than
      cyclophosphamide for the short-and medium-term treatment of lupus nephritis but
      that long-term data are available only for cyclophosphamide. New therapies are
      needed to reduce toxicity and the need for steroids and to offer the possibility
      of cure. Therapies under investigation include other immunosuppressive agents,
      anti-cellular therapies, drugs that modify cell-cell interactions, (anti
      )cytokine therapy, hormone therapy and lupus-specific immunomodulation. Rituximab
      has shown promise in patients refractory to conventional immunosuppression, which
      suggests that targeting B cells may be successful. Other anti-cell therapies
      include epratuzumab, belimumab and alemtuzumab. Anti-cytokine approaches include
      tumour necrosis factor alpha blockade with infliximab, anti-interleukin 6
      receptor therapy with tocilizumab and interferon-alpha blockade. As antidouble
      stranded DNA antibodies correlate with flares of lupus nephritis, they may
      represent another therapeutic target--as do monocyte chemoattractant protein-1
      and protein kinase CK2. Therapeutic options to prevent damage in lupus nephritis
      include non-immunosuppressive treatments aimed at reducing cardiovascular risk
      (such as statins, angiotensin-converting enzyme inhibitors and aspirin). As was
      the case with rheumatoid arthritis, a change in therapeutic aims--from survival
      through prevention of renal failure to induction of remission--may modify
      outcomes. EULAR's guidelines state that renal biopsy is the best monitor of
      clinical outcome in lupus nephritis, as immunological tests have limited
      predictive value. Measurement of urinary mRNA for cytokine and growth factor
      genes may provide a more sensitive, non-invasive method of monitoring therapeutic
      response.

PMID- 17432112
TI  - Exploring new territory: the move towards individualised treatment.
AB  - The main goal of therapy for lupus nephritis is to achieve remission, as this has
      a major impact on patient and renal survival. Furthermore, early treatment
      success has been shown to improve long-term prognosis. This has traditionally
      been achieved with intravenous cyclophosphamide, but recent data show that
      mycophenolate mofetil is equally effective and causes fewer adverse effects.
      Research is ongoing to find new treatment targets. Possible future therapies
      include monoclonal antibodies against CD20 (rituximab), CD22 (epratuzumab) and
      CD40, and therapies targeted at cytokine secretion, immunoglobulin secretion, B
      cell maturation and T-cell proliferation and differentiation. Rituximab has shown
      promise in patients with active proliferative lupus nephritis, which suggests
      that B-cell depletion may be successful. Anti-double-stranded DNA antibodies
      correlate with flares of lupus nephritis and may represent another therapeutic
      target. Therapy with LIP 394, which crosslinks anti-double-stranded DNA
      antibodies in solution or on the B-cell surface, has been shown to reduce flares.
      Cardiovascular disease is a major cause of mortality in systemic lupus
      erythematosus, and this must also be addressed if long-term outcomes are to be
      improved. Many patients with systemic lupus erythematosus have subclinical
      atherosclerosis quite early in the disease course, and the risk of coronary
      artery disease at any level of traditional cardiovascular risk factors is higher
      than in the general population. Specific lupus-associated risk factors include
      the inflammatory process itself and anticardiolipin antibodies. Possible
      strategies to reduce the risk include reduction of disease activity to improve
      endothelial function and reduction of steroid dose whenever possible. Therapy
      with aspirin or statins may be another possibility. Thus treatment of lupus
      nephritis is evolving from standardised therapy to individualised therapy based
      on analysis of organ involvement, risk factors and cytokine, antibody or cell
      profiles.

PMID- 17432113
TI  - Early development of the human pelvic diaphragm.

PMID- 17432114
TI  - The neuregulin-I/ErbB signaling system in development and disease.
AB  - Neuregulins (NRGs) comprise a large family of EGF-like signaling molecules
      involved in cell-cell communication during development and disease. The
      neuregulin family of ligands has four members: NRG1, NRG2, NRG3, and NRG4.
      Relatively little is known about the biological functions of the NRG2, 3, and 4
      proteins. In contrast, the NRG1 proteins have been demonstrated to play important
      roles during the development of the nervous system, heart, and mammary glands.
      For example, NRG1 has essential functions in the development of neural crest
      cells and some of their major derivatives, like Schwann cells and sympathetic
      neurons. NRG1 controls the trabeculation of the myocardial musculature and the
      ductal differentiation of the mammary epithelium. Moreover, there is emerging
      evidence for the involvement of NRG signals in the development and function of
      several other organ systems, and in human disease, including breast cancer and
      schizophrenia. Many different isoforms of the Neuregulin-1 gene are synthesized.
      Such isoforms differ in their tissue-specific expression patterns and their
      biological activities, thereby contributing to the great diversity of the in vivo
      functions of NRG1. Neuregulins transmit their signals to target cells by
      interacting with transmembrane tyrosine kinase receptors of the ErbB family. This
      family includes four members, the epidermal growth factor receptor (EGF-R, ErbB1,
      ErbB2, ErbB3, and ErbB4). Receptor-ligand interaction induces the
      heterodimerization of receptor monomers, which in turn results in the activation
      of intracellular signaling cascades and the induction of cellular responses
      including proliferation, migration, differentiation, and survival or apoptosis.
      In vivo, functional NRG1 receptors are heterodimers composed of ErbB2 with either
      an ErbB3, or ErbB4 molecule. The tissue-specific distribution of the different
      receptor types further contributes to the diversity and specificity of the
      biological functions of this signaling pathway. It is a typical feature of the
      Neuregulin-1/ErbB signaling pathway to control sequential steps during the
      development of a particular organ system. For example, this pathway functions in
      early precursor proliferation, maturation, as well as in the myelination of
      Schwann cells. The systematic analysis of genetic models that have been
      established by the help of conventional as well as conditional gene targeting
      strategies in mice was instrumental for the uncovering of the multitude of
      biological functions of this signaling system. In this review the basic biology
      of the Neuregulin-1/ErbB system and how it relates to the in vivo functions were
      discussed with special emphasis to transgenic techniques in mice.

PMID- 17432115
TI  - [Current research status of image-guided neurosurgery].
AB  - Image-guided neurosurgery is playing a more and more important role in modern
      neurosurgical therapy. The current trend is to construct an open platform for
      image-guided neurosurgery, to make applied researches of various new therapeutic
      techniques, and finally to integrate them into the clinical image-guided
      neurosurgery system.

PMID- 17432116
TI  - [Preliminary study on force feedback of acupuncture in virtual reality based on
      the visible human].
AB  - This paper discusses the application of virtual reality technology in the 3-D
      visible human body and acupuncture research. Based on the 3-D visible human fused
      with the localization information and hierarchy of acupoints, the paper analyzes
      the force against the needle and haptic rendering during the needle manipulation
      according to the physical properties of different tissues. A haptic model is
      constructed to demonstrate the force behaviors during acupuncture, and the force
      will be produced and passed to the manipulator by a force feedback device. It
      enriches the contents of 3-D visible human project, provides a dynamic simulation
      instrument for acupuncture teaching, and supplies a platform for acupuncture
      research.

PMID- 17432117
TI  - [A PC-based 3D stereoscopic medical visualization system].
AB  - In this paper, a low-cost PC-based, high-quality and interactive 3D stereoscopic
      medical visualization system is presented, which can be clinically used for
      diagnosis and surgical planning. The algorithms of direct volume rendering have
      been improved for realization with the programmable graphics hardware under PC
      environment. Local illumination, classification and non-polygonal iso-surface
      rendering are also incorporated into the system in appropriate consideration of
      both high-quality rendering and real-time interaction. The medical visualization
      system has been applied to the neurosurgical and orthopedic planning and the
      effectiveness has been clinically proved.

PMID- 17432118
TI  - [VTK-based free multi-planar reformation].
AB  - This paper introduces the development of the Free-MPR module, based on VC++6.0
      environment and VTK5.0, and on Windows XP platform. The Free-MPR module can
      adjust freely the display plane according to the change of the visual angle, and
      implement the free multi-planar reformation.

PMID- 17432119
TI  - [3D reconstruction of the heart model based on the region growing segmentation].
AB  - The technique introduced in this paper is applied in the endocardial catheter
      operation, which describes the 3D heart model reconstruction before the operation
      for the endocardial navigation. After a series of CT images of the thorax are
      processed, an accurate 3D endocardial model can be reconstructed. At first, the
      series of 2D CT images are preprocessed for denoising and the enhancement,then
      they are constructed as the volume data. After the region growing segmentation in
      the 3D volume data according to the grey value of the voxel in the heart cavity,
      the heart surface rendering is got and the 3D model of endocardial cavity is
      reconstructed.

PMID- 17432120
TI  - [Finite element method-based optimal design of MRI permanent magnet].
AB  - This paper presents a simulation method to study and improve the technology of
      designing magnets. With the finite element method, it analyzes the magnetic field
      distribution of the magnet model constructed by CAD software. Based on the
      distribution characteristics of magnetic field, the redundancy parts of the
      magnet configuration are removed accurately. The experiment results show that
      this method can significantly lighten the magnet.

PMID- 17432121
TI  - [Study on an epilepsy EEG processing system based on independent component
      analysis (ICA)].
AB  - An epilepsy EEG processing system designed based on Independent Component
      Analysis (ICA) is introduced in the paper, in order to meet the requirements of
      epileptic screening in clinical medicine. The system adopts module structure and
      virtual instrument technology, its hardware is mainly configured in the signal
      detecting box, data are exchanged between the box and the notebook computer or
      personal digital assistant (PDA) through certain digital interface, and ICA is
      executed in the notebook computer or PDA. The virtual EEG processing system based
      on ICA is able not only to perform ICA algorithms easily, but also to improve the
      developing efficiency greatly, and it is suitable for disease screening on a
      large scale.

PMID- 17432122
TI  - [Design of a wireless fetal electrocardiogram monitoring system based on
      S3C2410].
AB  - This paper introduces a new fetal electrocardiogram monitoring system based on
      S3C2410 and telecommunication, and its framework and flow chart. Based on the
      genetic algorithm, the improved IIR adaptive filter achieves the non-invasive,
      real-time extraction of FECG. The system provides the reliable gist for the
      diagnosis of fetal congenital diseases. FECG extraction, S3C2410,
      telecommunication, genetic algorithm, IIR adaptive filter.

PMID- 17432123
TI  - [Design and development of a massaging machine for the lumbar vertebrae
      diseases].
AB  - This paper introduces the designing process of a massaging machine on the basis
      of Pro/Engineer. The machine has realized the virtual design and movement
      simulation for the product. It's computer-controlled system has greatly improved
      the automatic level of the massaging machine which has broad prospects for
      popularization and application.

PMID- 17432124
TI  - [A study on the bio-safety for nano-silver as anti-bacterial materials].
AB  - This article introduces antibacterial principle and antibacterial properties of
      silver nanoparticles, and makes a synthetical study of the bio-safety on nano
      silver dressing, nano-silver gel, nano-silver anti-bacterial powder and silver
      nanoparticles.

PMID- 17432125
TI  - [Application of FRET in fluorescence detection of FQ-PCR].
AB  - The theory of fluorescence resonance energy transfer (FRET) and methods of
      fluorescence detection in fluorescent-quantitative polymerase chain reaction (FQ
      PCR) are introduced in this article. Applications of FRET in fluorescence
      detection of PCR are emphatically discussed, and FRET research progress and
      future trends are pointed out too.

PMID- 17432126
TI  - [Advances of cryotherapy technology].
AB  - This article introduces cryosurgery devices, cryopreservation devices, some
      cryogenic freezing methods in medicine and the recent progress about cryotherapy
      technology.

PMID- 17432127
TI  - [The subchronic toxicity study on the biological amnion].
AB  - As the new type cornea ulcer renovation material, the biological amnion is to be
      implanted into the human body for a long time, a subchronic toxicity study in
      rats is made to evaluate its possibility of subchronic toxicity. The study is
      based on the requirements of "Biological Evaluation of Medical Devices, Part 11:
      Tests for systemic toxicity and Part 6: Tests for local effects after
      implantation". After the implantation of examples to be tested, animals were
      observed daily for mortality and 92 days later the possible subchronic toxicity
      was evaluated. And a necropsy was conducted and the selected organs were excised,
      weighed, and processed histologically. Body weights, organ weights, organ/body
      weight ratios, hematology values and clinical chemistry values were analyzed
      statistically. Results show that daily clinical observation, body weights,
      necropsy findings, organ weights and organ/body weight ratios were within
      acceptable limits in test and control treatment groups. There were no obvious
      changes in histopathology, hematology values or clinical chemistry values in
      either male or female rats and no notable differences between the biological
      amnion and the control amnion. This study proves that, the cornea ulcer
      renovation material, the biological amnion does not induce subchronic toxicity.

PMID- 17432128
TI  - [A discussion on the concentration assay for sodium chloride in bicarbonate
      dialysate].
AB  - This essay is to present an improvement on the concentration assay for sodium
      chloride in bicarbonate dialysate.

PMID- 17432129
TI  - [How to construct a safe storage environment for hospital informations].
AB  - This article outlines the methods of building a safe environment for the hospital
      information system, and protecting data in three levels. Firstly it is
      recommended to build a highly efficient and redundant hot spare system for
      program applications and the database, secondly to make a copy of log file from
      the current database to the emergent server used for the whole hospital is
      suggested,finally another emergent server should be provided for the outpatient
      department. And thus, once there are some problems with the whole network, it
      would undertake the urgent services of the hospital as an outpatient network.

PMID- 17432130
TI  - [Design and implementation of a system for transforming the NEMA 2.0 images into
      DICOM 3.0 images].
AB  - This paper introduces the design and implementation of a system which can get the
      NEMA2.0 image data from the hard disks of the imaging equipments directly,then
      analyzes and transforms these image data into the DICOM3.0 image data and sends
      them to the image server. The design has the advantages of reliable image
      quality, low cost and information.

PMID- 17432131
TI  - [Computation of the cross-sectional area of the cable in the power circuit of the
      X-ray machine].
AB  - The source impedance of the power circuit in the x-ray machine is analyzed in the
      paper and based on the voltage drop generated by the impedance, the cross
      sectional area of the cable is calculated. In the end, the cross-sectional areas
      of the cables, corresponding to their respective distances between the
      transformers and the switchboards are given.

PMID- 17432132
TI  - [Error and quality control in clinical electrolyte analysis measurements].
AB  - The source of measure error and how to control the quality, reduce error,
      increase examination quality are described in the paper in clinical electrolyte
      analysis and measurements. The related factors include patient readiness, sample
      collection and preparation, condition of the instrument and reagents, data
      management, result report and so on.

PMID- 17432133
TI  - [Advances in studies on Platycodon grandiflorum].
AB  - Platycodon grandiflorum, as the traditional Chinese medicine, has been employed
      for dispersing the lung and resolving phlegm soothing the throat, and promoting
      pus discharge in ancient days. Triterpenoids are its main effective constituents
      which have dominant activities on antitussive, expectorant, antitumor,
      antioxidant and immune enhancement. This paper has mainly reviewed the progress
      of P. grandiflorum on the processing in planting area, chemical constituents,
      quality standard, pharmacological effects and clinical application in recent ten
      years, which has provided the important references for its further study,
      exploitation and application.

PMID- 17432134
TI  - [Advances on study of treatment of lumbar disk herniation by Chinese medicinal
      herbs].
AB  - Lumbar disk herniation (LDH) is a common orthopaedic disorder. Many clinical and
      basic science researches have been conducted recently on using Chinese medicinal
      herbs to treat LDH. Literature review reveals that the common basic formulas
      include Duhuo Jisheng decoction (DHJST), Buyang Huanwu decoction (HYBWT),
      Shentong Zhuyu decoction (STZYT), Taohong Siwu decoction (THSWT), Yanghe
      decoction (YHT) and Tongdu Huoxue decoction (TDHXT). A basic formula can be
      modified by adding more herbs or removing some herbs from the formula according
      to clinical symptoms and traditional Chinese medicine (TCM) syndrome
      differentiation. Literatures show that herbal treatment have better clinical
      effects, the medicinal herbs make low-back pain, sciatica and low limb numbness
      disappeared or alleviated; and restore normal low limb sensation, muscle strength
      and daily activity. These formulas have also been used to treat LDH postoperative
      remaining pain, postoperative discitis, postoperative recurrent LDH, and to
      prevent epidural scar formation and dura mata adhesion. Herbs in these formulas
      include 5 categories of drugs classified by TCM. They are blood circulation
      promoting herbs for relieving pain; liver and kidney nourishing and tendons and
      bones strengthening herbs; blood circulation promoting herbs for unblocking
      collaterals; pathogenic wind and dampness expelling herbs; and qi invigorating
      herbs. These herbs have actions of analgesia, anti-inflammation,
      immunomodulation, phagocytosis of macrophages enhancement, blood circulation
      improvement, nerve protection, collagen synthesis enhancement. Future research
      needs to focus on the effects of herbs on four aspects: to enhance collagen
      synthesis in the disks and inhibit disk degeneration; to promote the resorption
      of herniated nucleus pulposus and epidural hemorrhage; to prevent nerve cell
      apoptosis and promote nerve cell regeneration, and to inhibit nociception in the
      nerve system.

PMID- 17432135
TI  - [Studies on biotransformation of arbutin by 4-hydroxy phenol in hairy root of
      Polygonum multiflorum].
AB  - OBJECTIVE: To study the biotransformation of arbutin by 4-hydroxy phenol in hairy
      root of Polygonum multiflorum. METHOD: 4-hydroxy phenol was used as substrate,
      the standard curve was made by HPLC, and the influences of the co-culture time,
      the concentration of substrate added and the volume of culture flasks on
      biotransformation of arbutin were measured by the index of the production yield
      and transform rate of arbutin. RESULT: Arbutin could be detected from both of the
      cultures and medium. The correlation curve of arbutin: Y = 440740X - 1.473 (r =
      0.9997). The production yield (2.22 g x L(-1)) and conversion ratio (81.45%) of
      arbutin reached the maximum amount as co-culture time at 72 h, substrate added in
      medium for 1100 mg x L(-1). Furthermore a large-scale culture of 3 L was also
      successful in our experiment. CONCLUSION: It was firstly to biosynthesis arbutin
      in hairy root of P. multiflorum. The production yield and trasfer rate of arbutin
      were increased largely. And large-scale production (3 L culture flask) of arbutin
      was achieved in the experiment and it would be valuable for the industrial
      production of arbutin by biotechnological method in the future.

PMID- 17432136
TI  - [Primary study on shapes of fruits and germination characters of seeds of Radix
      et Rhizoma Rhei].
AB  - OBJECTIVE: To explore the difference of the shapes of fruits and germination
      characters of seeds of Rheum palmatum, R. tanguticum and R. officinale. METHOD:
      The seeds of three Rheum species including wild and cultivation one were
      collected from different regions. Character of the fruits appearance were
      observed. The purification, weights per thousand seeds, content of moisture, seed
      vigor and different germination rates of Radix et Rhizoma Rhei were measured. The
      germination rates of the seeds of R. palmatum were determined under different
      temperature and hormone treatment . RESULT: It was markedly variant in shapes of
      the fruits, rates of germination and all quality characters of the three category
      of Radix et Rhizoma Rhei. As reported, the size of the fruit and seed and weights
      per thousand seeds of R. officinale was the biggest. The seed vigor and
      germination rate of R. palmatum caltivated in Ming county of Gangsu were 95.7%
      and 94% respectively. The rate of seed vigor was closely correlated with the rate
      of germination for other species. Results indicated that temperature had some
      effects on the germination, and there were obvious difference in the active
      effect of gibberellin, kinetin and 6-benzyl aminopurine on the germination of the
      seed. Our experimental results showed that the kinetin concentration of 50 x 10(
      6) g x L(-1) had the most active effect, and its rates of germination increase 18
      percent than the control one. CONCLUSION: Significant differences exist in the
      shapes of fruits, rates of germination of the seeds of Rheum, which are affected
      by the factors of temperatures and hormones. The result of this study provides
      scientific evidences for identify, growth and cultivation of Rheum.

PMID- 17432138
TI  - [Comparative study on transdermal osmosis in vitro of Aconitum brachypodium
      liniment, gel and patcher].
AB  - OBJECTIVE: To study the transdermal osmosis process of Aconitum brachypodum's
      liniment, gel and patcher to provide basis for selecting dosage form and
      controlling the quality. METHOD: Taking the cumulate rate of transdermal as
      index, a imitated Fick's diffusion device was used for the investigating the
      transdermal osmosis course of the three preparations. The best transdermal
      mathematics models are obtained and the relations between the transdermal course
      and the release course are analysed. RESULT: The three preparations have
      different characteristics of transdermal osmosis course. The liniment meets
      dynamics 0 order process, the gel and the patcher meet dynamic 0 order process of
      non-corroded drug system. And the relation is good cubic equation between their
      transdermal course and release course. CONCLUSION: The transdermal osmosis
      experiment in vitro for three preparations can provide basis for selecting dosage
      form and the quality control in future studies.

PMID- 17432137
TI  - [Study on dynamic accumulation of secondary metabolites content and isoenzyme
      activity during blossoming stages in Chrysanthemum morifolium originating from
      Wenxian county].
AB  - OBJECTIVE: To study the anabolic rule of secondary metabolites and dynamic
      activity of isoenzyme in Chrysanthemum morifolium originating from Wenxian county
      during blossoming stages. METHOD: The flavonoid, chlorogenic acid and anthocyanin
      content as well as the PAL, PPO and POD activity were determined in C. morifolium
      originating from Wenxian county during blossoming stages. RESULT AND CONCLUSION:
      The content of flavonoid and chlorogenic acid was the highest at 70% of full
      blossom, the anthocyanin at 50% and PPO activity at 30% with the same trend of
      two cultivars. Between the two cultivars, the trend of PAL and POD was different.
      The highest of "huaidabaiju" appeared at 70% and 30%, but that of "huaixiaobaiju"
      appeared at 50% and 50%.

PMID- 17432139
TI  - [Application of UV similarity in quality control of Chinese medical injection].
AB  - OBJECTIVE: To propose an algorithm of the similarity between UV-spectra for
      controlling the quality of Chinese medical injection. METHOD: The similarity is
      calculated base on the data of two UV-spectrum curves, thus the sample quality is
      evaluated according to the average value of the similarity of the UV-spectra
      between sample with each of standard samples; the proposed algorithm of the
      similarity is compared with cosine of vectorial angle and relative coefficient;
      the proposed method for quality evaluation of traditional Chinese injection is
      discussed with the method according to the chromatographic fingerprint
      similarity. RESULT: The calculated similarity with the proposed method can be
      sensitive to show the difference between UV-spectra. This proposed method for
      quality evaluation was applied for assessing quality of 14 batches of Xiangdan
      injection and the results well coincident with sample quality. CONCLUSION: The
      proposed method can be used to evaluate the quality of the Chinese medical
      injection according to the similarity of two UV-spectrum curves.

PMID- 17432140
TI  - [Fingerprints of different samples of processed Rhizoma Coptidi by HPLC].
AB  - OBJECTIVE: To set up the HPLC fingerprints of different samples of processed
      Rhizoma Coptidi (RC) in order to offer evidence for identifying different
      processed RC and preliminary discussion on processing mechanism. METHOD: Seven
      different samples of processed RC were determined by HPLC and the results were
      analyzed by Hierarchical clustering and similarity evaluation system for
      chromatographic fingerprint of TCM. RESULT: The characteristic of common peaks
      for fingerprints of different samples of processed RC is distinct, but there are
      differences among various processed RC. The different samples of processed RC
      were classified into two and the result of hierarchical clustering is correlated
      with the property of traditional Chinese drug. CONCLUSION: It is proved that the
      method which is convenient, rapid and repeat well can be used to identify
      different samples of processed RC. The change of property of different processed
      RC is related with processing adjuvant, the possible mechanism is that new
      components are produced or the contents of known components have changed due to
      the adjuvant during processing.

PMID- 17432141
TI  - [Orthogonal experiment using SFE-CO2 in extraction of essential oil from fresh
      Houttuynia cordata and analysis of essential oil by GC-MS].
AB  - OBJECTIVE: To optimize the extraction procedure of essential oil from H. cordata
      using the SFE-CO2 and analyze the chemical composition of the essential oil.
      METHOD: The extraction procedure of essential oil from fresh H. cordata was
      optimized with the orthogonal experiment. Essential oil of fresh H. cordata was
      analysed by GC-MS. RESULT: The optimize preparative procedure was as follow:
      essential oil of H. cordata was extracted at a temperature of 35 degrees C,
      pressure of 15,000 kPa for 20 min. 38 chemical components were identified and the
      relative contents were quantified. CONCLUSION: The optimum preparative procedure
      is reliable and can guarantee the quality of essential oil.

PMID- 17432142
TI  - [Preparation of inclusion complex of paeonol and beta-cyclodextrin by sealed
      control temperature method].
AB  - OBJECTIVE: In the present study, using paeonol as model drug, a new sealed
      control temperature method of preparing inclusion complex was developed, the
      effects of heating temperature, heating time, and crystallinity of beta
      cyclodextrin (beta-CD) on formation of inclusion complex and release of the drug
      were investigated. METHOD: A physical mixture of paeonol and beta-CD was sealed
      in a container, and heated at the desired temperature for the specified time. The
      inclusion complex of paeonol and beta-CD was confirmed by IR spectrum and powder
      X-ray diffraction. RESULT: The results indicated that the inclusion complex
      formation of paeonol beta-CD by sealed-control temperature method was affected by
      heating temperature, heating time, and crystallinity of beta-CD. The inclusion
      complex was able to inhibit sublimation of paeonol, and dissolution rate of
      paeonol was increased when the paeonol was included by beta-CD. CONCLUSION:
      Preparation of inclusion complex was simple and quick by sealed-control
      temperature method.

PMID- 17432143
TI  - [Determination of matrine, sophoridine and oxymatrine in Compound Kushen
      Injection by HPLC].
AB  - OBJECTIVE: To establish a high performance liquid chromatography (HPLC) method
      for determination of matrine, sophoridine and oxymatrine in Compound Kushen
      Injection. METHOD: Alltima amino column was used with acetonitrile-3% phosphoric
      acid-ethyl alcohol (80:10:10) as the mobile phase and the detection wavelength
      was at 220 nm. RESULT: The mean recovery of matrine, sophoridine and oxymatrine
      in Compound Kushen Injection was 99.51% (RSD 1. 58%), 99.24% (RSD 1.44%) and
      100.22% (RSD 1.85%), respectively. CONCLUSION: The method was simple, rapid,
      accurate and specific and suitable for quality control of the product.

PMID- 17432144
TI  - [Determination of bufothionine in skin of Bufo bufo gargarizans and Huachansu
      injection].
AB  - OBJECTIVE: To establish a HPLC method for bufothionine in the skin of Bufo bufo
      gargarizans and Huachansu injection. METHOD: The samples were separated using a
      Lichrosob C18 column with CH3CN-H2O (10:90) as mobile phase. Flow rate was at 1.0
      mL x min (-1) and the detection wavelength was at 225 nm. RESULT: The calibration
      curve of bufothionine was linear over the range of 0.0772-0.4632 microg and the
      average recovery was 99. 2%. The contents of bufothionine were fluctuated from
      36.4-641.8 microg x g(-1) in the skin of Bufo bufo gargarizans and 22.47-33.16
      microg x mL(-1) in Huachansu injection, respectively. CONCLUSION: The contents of
      bufothionine were greatly different between cultured and wild species. The method
      was suitable for the quality control of the skin of Bufo bufo gargarizans and its
      preparation.

PMID- 17432145
TI  - [GC-MS analysis of essential oil from anthodiums of Chrysanthemum morifolium
      processed by microwave-airflow and steam calefaction].
AB  - OBJECTIVE: Analysis of the constituents of the essential oil extracted from the
      flowers of the Chrysanthemum morifolium processed by the microwave-airflow and
      the calefaction after steam process from the State Chrysanthemum GAP bases in
      Zhejiang Province and to provide scientific basis for quality control. METHOD:
      The essential oil was 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 the microwave
      airflow dried sample and the calefactively dried sample after steam process, 119
      and 175 components were detected, among them fifty and fifty-five components were
      identified, which were composed of 67.89% and 63.64% of the total essential oil,
      respectively. CONCLUSION: The yield of the essential oil extracted from the
      microwave-airflow dried sample was 0.40%, and that from the calefactively dried
      sample after steam process was 0. 19%. The former is 2.1 times higher than the
      latter. The components of the essential oil are similar and there are differences
      between the content of corresponding compounds in the two samples. The results
      showed that application of microwave-airflow combined drying technology remained
      original and essential constituents. The production benefit was improved greatly.
      The grade and quality of C. morifolium enhanced, and it's market selling price
      was increased compared to the traditional drying calefaction after steam process.

PMID- 17432146
TI  - [Investigation on dissolution of cinnabar in vitro].
AB  - OBJECTIVE: To study effects of different chemical factors in gastrointestinal
      tract, i.e. pH, protein, amino acid, ionic strength, Na2S, on the dissolution of
      cinnabar. METHOD: The content of total mercury in various dissolution of cinnabar
      were analyzed by UV/VIS Spectrophotometer. The particle distributions in
      dissolution of cinnabar were measured by Laser Particle Size Analyzer. The
      constituents of dissoluble substance of cinnabar in presence of Na2S were
      determined using ESI-MS. RESULT: The solubility of cinnabar could be increased
      significantly in the presence of Na2S/So, and strong acidic pH, respectively.
      While the influence of thiol amino acid on promoting dissolution remains
      relatively low. Cinnabar didnt dissolve mainly in the form of nanoparticle.
      CONCLUSION: We postulated that cinnabar could be dissolved in various forms of
      mercury complexes containing sulphur.

PMID- 17432147
TI  - [Studies on chemical constituents from the fruiting bodies of Ganoderma sinense
      Zhao, Xu et Zhang].
AB  - OBJECTIVE: To study the chemical constituents from the fruiting bodies of
      Ganoderma sinense Zhao, Xu et Zhang. METHOD: To isolated the compounds by silica
      gel and sephadex LH -20 column chromatography and their structures were elucidate
      by means of spectral analysis. RESULT: Six sterols, one fatty acid and one of
      diketopiperazines were obtained from CHCl3 fraction of EtOH extract and
      identified as ergosta-7, 22-dien-3beta-ol (1), ergosterol (2), 6, 9
      epidioxyergosta-7, 22-dien-3beta-ol (3), 5, 8-epidioxiergosta-6, 22-dien-3beta-ol
      (4), ergosta-7, 22-dien-3-one (5), beta-sitosterol (6), alpha
      Hydroxytetracosanoic acid (7), cyclo (D-Pro-D-Val) (8). CONCLUSION: Componds 1-8
      are isolated from G. sinense Zhao, Xu et Zhang for the first time.

PMID- 17432148
TI  - [Study on anti-tumor effect of dry and fresh Gekko swinhonis freeze-dried powders
      on mice sarcoma S180 and acute toxicity testing of two powders].
AB  - OBJECTIVE: To investigate the anti-tumor activity of dry Gekko swinhonis freeze
      dried powder (DGFP) and fresh G. swinhonis freeze-dried powder (FGFP) on mice
      sarcoma S180 and acute toxicity testing of the two powders. METHOD: Mice
      xenotransplant model of sarcoma S180 was established. Eighty mice were randomly
      divided into 8 groups. Control group were orally administrated by saline, another
      intraperitoneally injected with 5-Fu, the other six groups were orally
      administrated by DGFP and FGFP, each at three different doses (low, moderate and
      high). Rate of restraining tumor, index of thymus and spleen were calculated
      after 10 days' treatment. Acute toxicity testing tried to figure out LDs and LD,
      of DGFP and FGFP. RESULT: The restraining tumor rates of DGFP and FGFP each at
      three doses were 31.4%, 50.8%, 37.7% and 14.8%, 19.1%, 54.7%. DGFP and FGFP
      elevated the thymic weight and thymic index of the mice to different extent.
      There were no significant differences among the eight groups in their spleen
      weight and spleen index. Acute toxicity testing did not figure out LD50 of DGFP
      and FGFP. In LD0 test, the administrating dosages of DGFP and FGFP given to the
      mice were both more than 2000 times than those given to patients on clinic. The
      result showed nothing abnormal in DGFP group. Compared with the DGFP and control
      group there was only a significant body weight decrease (P < 0.01) in the FGFP
      group in the first three days. However, on the fifth day and the seventh day
      there was no significant difference. CONCLUSION: DGFP and FGFP have conspicuous
      anti-tumor effects in vivo. The mechanism may be related to the elevated cellular
      immune function. Acute toxicity testing reveals that DGFP and FGFP are quite safe
      for conventional oral use on clinic.

PMID- 17432149
TI  - [Astragalus membranaceus promote expression of insulin-like growth factor 1 in
      rat model of olivo-cerebellar degeneration].
AB  - OBJECTIVE: To observe the effect of Astragalus membranaceus (AM) on insulin-like
      growth factor 1 (IGF-1) expression in a rat model of olivo-cerebellar
      degeneration and assess the neuroprotective actions of AM meanwhile. METHOD: Rats
      model of olivo-cerebellar degeneration was established by using 3-acetylpyridine.
      The effect of AM on the expression of Calbindin D-28K in inferior olive (IO)
      neurons by immunohistochemistry, the serum IGF-1 level by Elisa, the IGF-1 mRNA
      level in the cerebellum by RT-PCR were detected respectively. RESULT: AM
      effectively improve the serum IGF-1 level, Cerebellar IGF-1 mRNA level and the
      survival of the 10 neurons in a rat model of olivo-cerebellar degeneration, even
      at a lower dose (9 g x kg(-1)), and the effect was in a dose-dependent manner.
      CONCLUSION: AM could effectively upregulate the IGF-1 expression in the rat model
      of olivo-cerebellar degeneration, and have neuroprotective effect on IO neurons.

PMID- 17432150
TI  - [Effects of among compositions of Herba Ephedrae decoction on genic xpression of
      5-lipoxygenase activating protein, IL-4 and leukotriene C4 in asthmatic mice].
AB  - OBJECTIVE: To explore the regularity of recipe composition by observing
      inhibitory effects on the genic expression of 5-lipoxygenase activating protein,
      IL-4 and the leukotriene C4 in asthmatic mice. METHOD: The mice were challenged
      with OVA and administered ig with the Herba Ephedrae decoction (HED), separated
      compositions (2500 mg x kg(-1), calculated by Herba Ephedrae) and dexamethasone
      (2 mg x kg(-1)) respectively once daily for seven days. The real-time
      fluorescence quantitative PCR method was employed to measure the contents of FLAP
      mRNA and IL-4 mRNA expressions in lung and the ELISA method was used to determine
      the content of LTC4 in the washing solution of pulmonary alveolus and bronchi.
      RESULT: In the lung of asthma mice, the expressions of FLAP and IL-4 and the
      content of LTC4 were significantly augmented compared with the control group. The
      HED and the separated compositions could suppress the expressions of FLAP and IL
      4 and LTC4 release to a great extent in mice. CONCLUSION: The HED had the
      remarkable effects of antianaphylaxis asthma and the original formula HED worked
      best. These results confirmed the rationality and scientific level of HED.

PMID- 17432151
TI  - [Protective action of effective components of Huanglian Jiedu decoction on
      hypoxia and reoxygenation injury in cultured rat cerebral microvascular
      endothelial cells].
AB  - OBJECTIVE: To investigate the protective effect of geniposide, baicalin and
      berberine for the rat cerebral microvascular endothelial cell. METHOD: The model
      of hypoxia and reoxygenation injury in rat cerebral microvascular endothelial
      cells in vitro was established. Both normal and model cells were treated with
      geniposide (1.024, 0.512, 0.256, 0.128, 0.064, 0.032, 0.016, 0.008 micromol x mL(
      1)), baicalin (0.224, 0.112, 0.056, 0.028, 0.014, 0.007, 0.003 micromol x mL(-1))
      and berberine (0.192, 0.096, 0.048, 0.024, 0.012, 0.006, 0.003 micromol x mL(
      1)). Cell activity was measured by methyl thiazolyl tetrazolium (MTT) test.
      RESULT: After hypoxia/hypoglycemia cultures for 4 hour and reoxygenation for 12
      hour, geniposide (0.128, 0.064, 0.032 micromol x mL(-1)), baicalin (0.028, 0.014,
      0.007 micromol x mL(-1)) and berberine (0.024, 0.012, 0.006 micromol x microL(-1)
      could protect the injuried cerebral microvascular endothelial cells. CONCLUSION:
      Appropriate concentration of geniposide, baicalin and berberine, which are
      effective components of Huanglian Jiedu decoction, could protect the injuried
      cerebral microvascular endothelial cells.

PMID- 17432152
TI  - [Effect of Xuesaitong drop pills on experimerntal thrombosis and thrombolysis in
      rats].
AB  - OBJECTIVE: To study the effect and the mechanism of Xuesaitong drop pills (total
      saponins in Radix Notoginseng; XDP) on experimental thrombosis, thrombolysis and
      blood theology. METHOD: First, the rats were randomly divided into five groups:
      control, XDP (90, 30, 10 mg x kg(-1)), Xuesaitong tablet (XP) 30 mg x kg(-1).
      Then the effect of the drugs on thrombus and thrombosis was studied after the
      ratsthrombosis was induced by the arteriovenous shunt. Second, the rats were
      randomly divided into seven groups: model, XDP (90, 30, 10 mg x kg(-1)), XT (90,
      30 mg x kg(-1)), lumbrukinase capsule. Then the effect of the drugs on thrombus
      and thrombosis was studied after the rats'thrombosis was induced by the
      electrical stimulation of common carotid artery. Third, the rats were randomly
      divided into six groups: control, model, XDP (80, 40 mg x kg(-1)), XT (40, 20 mg
      x kg(-1)). Then the effect of the drugs on blood circulation promoting was
      observed after the rats'acute blood stasis induced by adrenalin and icy water.
      RESULT: XDP 90, 30 mg x kg(-1) could notably lighten the wet-weight and dry
      weight of thrombus in the arteriovenous shunt model in rats in a dose-dependent
      manner (P < 0.01). XDP 90 mg x kg(-1) with intragastric administration for 3 days
      had the satisfactory effect on thrombolysis after the rat's thrombosis was
      induced by the electrical stimulation of common carotid artery (P < 0.01). XDP
      80, 40 , 20 mg x kg(-1) reduced significantly erythrocyte aggregation (P < 0.01)
      and decreased the whole blood viscosity at low shear rate (P < 0.05). XDP 80, 40
      mg x kg(-1) reduced the whole blood viscosity at high shear rate and plasma
      viscosity (P < 0.05). XDP 80 mg x kg(-1) decreased the whole blood viscosity at
      high shear rate (P < 0.05). CONCLUSION: XDP can significantly inhibit the
      thrombosis and has the satisfactory effect on thrombolysis. One kind of the
      mechanism is related to the effect on blood rheology.

PMID- 17432153
TI  - What your leader expects of you.
AB  - The success of an executive team depends heavily on the relationships the boss
      has with his or her direct reports. Yet the leadership literature has had little
      to say about what is expected in those relationships-on either side. Larry
      Bossidy, formerly the chairman and CEO of Honeywell, and before that of
      AlliedSignal, shares what he calls "the CEO compact," detailing the behaviors a
      leader should look for in subordinates and what they should be able to expect in
      return. A CEO's best people, he says, know when a situation calls for them to get
      involved. They generate ideas-remembering that some of the best ones may sound
      crazy at first. They are willing to collaborate, putting the long-term good of
      the company above short-term goals of their divisions. They step up to lead
      initiatives, even if the outcome is uncertain. They develop leaders among their
      people, especially through direct involvement in performance appraisals. They
      stay current on world events and anticipate how those events may affect the
      company and its competition. They drive their own growth by exposing themselves
      to new people and ideas and by accepting demanding assignments. And they sustain
      these behaviors in bad times as well as good. On the other side of the compact,
      the boss should provide clarity of direction; set goals and objectives; give
      frequent, specific, and immediate feedback; be decisive and timely; demonstrate
      honesty and candor; and offer an equitable compensation plan. Executives who
      aren't lucky enough to have such a boss can create a compact with their own
      subordinates, Bossidy says, and demonstrate by example. The result will be to
      improve team and company performance and accelerate individual growth.

PMID- 17432154
TI  - Finding your next core business.
AB  - How do you know when your core needs to change? And how do you determine what
      should replace it? From an in-depth study of 25 companies, the author, a strategy
      consultant, has discovered that it's possible to measure the vitality of a
      business's core. If it needs reinvention, he says, the best course is to mine
      hidden assets. Some of the 25 companies were in deep crisis when they began the
      process of redefining themselves. But, says Zook, management teams can learn to
      recognize early signs of erosion. He offers five diagnostic questions with which
      to evaluate the customers, key sources of differentiation, profit pools,
      capabilities, and organizational culture of your core business. The next step is
      strategic regeneration. In four-fifths of the companies Zook examined, a hidden
      asset was the centerpiece of the new strategy. He provides a map for identifying
      the hidden assets in your midst, which tend to fall into three categories:
      undervalued business platforms, untapped insights into customers, and
      underexploited capabilities. The Swedish company Dometic, for example, was
      manufacturing small absorption refrigerators for boats and RVs when it discovered
      a hidden asset: its understanding of, and access to, customers in the RV market.
      The company took advantage of a boom in that market to refocus on complete
      systems for live-in vehicles. The Danish company Novozymes, which produced
      relatively low-tech commodity enzymes such as those used in detergents, realized
      that its underutilized biochemical capability in genetic and protein engineering
      was a hidden asset and successfully refocused on creating bioengineered specialty
      enzymes. Your next core business is not likely to announce itself with fanfare.
      Use the author's tools to conduct an internal audit of possibilities and pinpoint
      your new focus.

PMID- 17432155
TI  - Promise-based management: the essence of execution.
AB  - Critical initiatives stall for a variety of reasons--employee disengagement, a
      lack of coordination between functions, complex organizational structures that
      obscure accountability, and so on. To overcome such obstacles, managers must
      fundamentally rethink how work gets done. Most of the challenges stem from broken
      or poorly crafted commitments. That's because every company is, at its heart, a
      dynamic network of promises made between employees and colleagues, customers,
      outsourcing partners, or other stakeholders. Executives can overcome many
      problems in the short-term and foster productive, reliable workforces for the
      long-term by practicing what the authors call "promise-based management," which
      involves cultivating and coordinating commitments in a systematic way. Good
      promises share five qualities: They are public, active, voluntary, explicit, and
      mission based. To develop and execute an effective promise, the "provider" and
      the "customer" in the deal should go through three phases of conversation. The
      first, achieving a meeting of minds, entails exploring the fundamental questions
      of coordinated effort: What do you mean? Do you understand what I mean? What
      should I do? What will you do? Who else should we talk to? In the next phase,
      making it happen, the provider executes on the promise. In the final phase,
      closing the loop, the customer publicly declares that the provider has either
      delivered the goods or failed to do so. Leaders must weave and manage their webs
      of promises with great care-encouraging iterative conversation and making sure
      commitments are fulfilled reliably. If they do, they can enhance coordination and
      cooperation among colleagues, build the organizational agility required to seize
      new business opportunities, and tap employees' entrepreneurial energies.

PMID- 17432156
TI  - The leadership team: complementary strengths or conflicting agendas?
AB  - Senior leadership teams whose members play complementary roles have been
      chronicled as far back as Homer's account of the Trojan War: Although King
      Agamemnon commanded the Greek army, Achilles, Odysseus, and Nestor each played a
      distinct role in defeating Troy. Today, complementary-leadership structures are
      common and, in some cases, even institutionalized. Think of a CEO concerned
      mainly with external issues and a COO who focuses internally. The authors
      describe four kinds of complementarity: task, expertise, cognitive, and role. The
      two top executives at the software company Adobe Systems, for example, represent
      the second kind. As CEO, Bruce Chizen draws on his sales and marketing knowledge,
      while COO Shantanu Narayen adds his engineering and product development
      expertise. Roberto Goizueta, formerly the CEO of Coca-Cola, and Douglas Ivester,
      his COO (who later became CEO), were famous examples of the fourth type:
      Goizueta, the diplomat, maintained good relations with external stakeholders;
      Ivester, the warrior, drove the company to defeat the competition. Bringing
      together two or more people with complementary strengths can compensate for the
      natural limitations of each. But with the benefits comes the risk of confusion,
      disagreement about priorities, and turf battles. Leadership succession also
      presents substantial challenges, especially when a COO or president who has
      worked in a complementary fashion with the CEO moves into the top role. An
      organization's board of directors and CEO can manage the risks by fostering a
      shared vision, common incentives, communication, and trust. They can also ensure
      smooth succession processes in various ways, such as brokering a gradual transfer
      of responsibilities or allowing the CEO and the COO to share duties as long as
      they maintain the logic of complementarity.

PMID- 17432157
TI  - Avoiding integrity land mines.
AB  - How does a large multinational keep thousands of employees, operating in hundreds
      of countries, honest in a high-pressure business environment? As the chief legal
      officer at General Electric for nearly 20 years, Ben Heineman was part of the
      senior management group that sought to do just that--to make sure its executives
      and employees are moved to do the right thing as strongly as they are motivated
      to make their numbers. Heineman describes a set of systems that combine the
      communication of clear expectations with oversight, deterrence, and incentives.
      Nowhere are the expectations higher--and the sanctions more powerful--than for
      top executives. Heineman recounts example after example of senior leaders
      terminated for ethical lapses even when the business consequences of doing so
      were painful--and even when they had no direct knowledge of the violations
      occurring on their watch. To make expectations clear throughout the company, GE
      has systematically sought to set uniform standards that stay well ahead of
      current legal developments and stakeholders' changing attitudes about corporate
      accountability. Responsibility for implementing those standards, which are
      embedded in GE's operating practices, rests with the business leaders in the
      field. Oversight is both methodical and multifaceted. A host of auditing and
      assessment systems enables GE to compare the performance of its various business
      units against one another and against industry benchmarks. Perhaps the most
      powerful is the company's ombudsman system, which doesn't just allow but requires
      employees to lodge concerns. Failures to report into the system or up the line,
      or retaliation in any form, are firing offenses. The current intense focus on
      board-level governance has missed the point, Heineman argues. It is time to shift
      the debate from board oversight of the CEO to how top company leaders can most
      effectively infuse integrity at all levels of the corporation.

PMID- 17432158
TI  - The process audit.
AB  - Few executives question the idea that by redesigning business processes--work
      that runs from end to end across an enterprise--they can achieve extraordinary
      improvements in cost, quality, speed, profitability, and other key areas Yet in
      spite of their intentions and investments, many executives flounder, unsure about
      what exactly needs to be changed, by how much, and when. As a result, many
      organizations make little progress--if any at all--in their attempts to transform
      business processes. Michael Hammer has spent the past five years working with a
      group of leading companies to develop the Process and Enterprise Maturity Model
      (PEMM), a new framework that helps executives comprehend, formulate, and assess
      process-based transformation efforts. He has identified two distinct groups of
      characteristics that are needed for business processes to perform exceptionally
      well over a long period of time. Process enablers, which affect individual
      processes, determine how well a process is able to function. They are mutually
      interdependent--if any are missing, the others will be ineffective. However,
      enablers are not enough to develop high-performance processes; they only provide
      the potential to deliver high performance. A company must also possess or
      establish organizational capabilities that allow the business to offer a
      supportive environment. Together, the enablers and the capabilities provide an
      effective way for companies to plan and evaluate process-based transformations.
      PEMM is different from other frameworks, such as Capability Maturity Model
      Integration (CMMI), because it applies to all industries and all processes. The
      author describes how several companies--including Michelin, CSAA, Tetra Pak,
      Shell, Clorox, and Schneider National--have successfully used PEMM in various
      ways and at different stages to evaluate the progress of their process-based
      transformation efforts.

PMID- 17432159
TI  - Human due diligence.
AB  - Most companies do a thorough job of financial due diligence when they acquire
      other companies. But all too often, deal makers simply ignore or underestimate
      the significance of people issues in mergers and acquisitions. The consequences
      are severe. Most obviously, there's a high degree of talent loss after a deal's
      announcement. To make matters worse, differences in decision-making styles lead
      to infighting; integration stalls; and productivity declines. The good news is
      that human due diligence can help companies avoid these problems. Done early
      enough, it helps acquirers decide whether to embrace or kill a deal and determine
      the price they are willing to pay. It also lays the groundwork for smooth
      integration. When acquirers have done their homework, they can uncover capability
      gaps, points of friction, and differences in decision making. Even more
      important, they can make the critical "people" decisions-who stays, who goes, who
      runs the combined business, what to do with the rank and file-at the time the
      deal is announced or shortly thereafter. Making such decisions within the first
      30 days is critical to the success of a deal. Hostile situations clearly make
      things more difficult, but companies can and must still do a certain amount of
      human due diligence to reduce the inevitable fallout from the acquisition process
      and smooth the integration. This article details the steps involved in conducting
      human due diligence. The approach is structured around answering five basic
      questions: Who is the cultural acquirer? What kind of organization do you want?
      Will the two cultures mesh? Who are the people you most want to retain? And how
      will rank-and-file employees react to the deal? Unless an acquiring company has
      answered these questions to its satisfaction, the acquisition it is making will
      be very likely to end badly.

PMID- 17432160
TI  - Democratic agenda places medicare advantage at risk.

PMID- 17432161
TI  - Unable to carry cost burden, payers seek other remedies.

PMID- 17432162
TI  - Plans, PBMS, employers prod docs to e-prescribe.

PMID- 17432163
TI  - Achieving quality measures yields high bonuses for U.K. physicians.

PMID- 17432164
TI  - Managing cancer treatment begins before diagnosis.

PMID- 17432165
TI  - Plans put greater emphasis on cancer management.

PMID- 17432166
TI  - Give patients the tools to make good decisions.

PMID- 17432167
TI  - NCQA shifts focus on physician performance.

PMID- 17432168
TI  - Applying the planned care model to intimate partner violence.
AB  - PURPOSE: This article presents the steps for organizing a health organization's
      response to intimate partner violence (IPV) according to the Planned Care Model
      (PCM). IPV is common and costly and results in poor physical and mental health
      outcomes for victims and their families. Because most care is not acute, a
      planned approach that crosses systems may result in more comprehensive and higher
      quality care. Community collaboration with IPV agencies is especially critical.
      The health care organization must make IPV a priority and set policies and
      systems to identify and manage patients, train staff, and measure, monitor, and
      provide feedback on outcomes. Other key PCM components include: practice design-
      design systems to identify and track victims, stratify risk, and coordinate care;
      evidence-based decision support--choose validated IPV screening questions and
      guidelines for identification, management, and referral and make them available
      in a systematic way with ongoing assessment and feedback to providers and other
      members of the health care team; patient self-management--self-man-agement
      materials should be selected and disseminated to those working with IPV victims;
      and data information systems--these should support a confidential patient
      registry and efforts to audit and provide feedback about identification and
      referral efforts. Process and outcome measures based on the management guidelines
      and protocols should be developed and monitored, and the results disseminated.
      CONCLUSION: Adapting PCM for the management of IPV stretches the traditional
      acute approach to IPV of screen-identify-refer. It expands the PCM into new
      realms, including embracing new partners, trying innovative ways to measure
      return on investment, grappling with ethical dilemmas, and designing a
      multifactorial evaluation across systems.

PMID- 17432169
TI  - Care management data hard to come by.

PMID- 17432170
TI  - Revolutionary heart valves, sutures from miracle substance--polyester.

PMID- 17432171
TI  - Plans, PBMS step up infotech initiatives.

PMID- 17432172
TI  - [Observation and description--neurology as a field work science].
AB  - Scientific researches in medicine could be classified into two categories; an
      experimental medicine or a science for solving various problems and a field work
      medicine for discovering new problems. Although both fields of medical researches
      are requisite for the real progress of medicine, the importance of the latter
      field is now a little neglected. As the President of the 47th annual meeting of
      Japanese Society of Neurology, I chose "Quo vadis, Neurologia" quoting
      Sienkiewicz as a grand theme of the meeting and tried to find out answers to
      secure the future of clinical neurology. This presidential lecture is to stress
      the importance of a field work type of clinical researches in neurological
      sciences to which we, clinical neurologists, have the privileges of daily access.

PMID- 17432173
TI  - [Historical review of development of neuro-historogical techniques and three
      dimensional reconstruction of individual neurons].
AB  - The image of neuron proposed by Barker in 1899 is until now useful. However this
      image could be said to be only a schema based on the data obtained by various
      histological techniques developed in the latter half of the nineteenth century.
      Although thereafter many careful observations on neuronal architecture have been
      made, much still remains to be done for revealing their true geometry. In our
      histological analysis with Golgi-stained materials in the cat, it was found that
      the reflecting illumination showed the somal surface and its relationship with
      the dendrites in clear relief. With this method it was possible to develop a new
      approach for photogrammetric representation of the neuronal soma as well as for
      following the total course of dendrites in successive serial sections that had
      been cut off by the microtome knife. This has provided a means for estimating
      precisely the dimensions of the neuron. In addition, by means of the intra
      axonally injection of HRP in cats, the intramedullary course of physiologically
      identified afferent fibers originating from various muscles in lumbosacral region
      was also reconstructed three-dimensionally from serial sections. The results thus
      obtained revealed that the collaterals belonging to groups Ia, Ib and II fibers
      of the muscles examined showed some typical differences in their courses and in
      their terminations in the gray matter. The results of extra-cellular injection of
      BDA (Sato F. et al., 2000) into the Nucl. subthalamicus in monkeys also cited as
      this sort of work. It should be emphasized that, whether classic manual method or
      more effective modern techniques are used, three-dimensional reconstruction is
      the most important factor for studying the comlete axonal geometry of individual
      neurons, of which effects may be said, at least at present, to be still
      methodologically incomplete.

PMID- 17432174
TI  - [Molecular genetics of inherited neuropathies].
AB  - To clarify the specific features and molecular mechanisms of five diseases that
      we previously reported, we reviewed recent progress in HMSN-P linked to
      chromosome 3, CMT4F caused by PRX, CMT4A caused by GDAP1, CMT4B2 caused by
      SBF2/MTMR13F, and SCAN1 caused by TDP1. HMSN-P is characterized by late onset,
      proximal dominant severe muscle weakness, fasciculations, muscle cramp and
      sensory involvement. HMSN-P is a primary neuronopathy. Mutations in periaxin are
      associated with a broad spectrum of demyelinating neuropathies including DSS, a
      sensory dominant form and early onset slowly progressive CMT. Pathologically,
      loss of myelinated fibers, demyelination, small onion bulb formations, tomacula
      formation and myelin foldings were seen in sural nerves. Absence of septate like
      junction in the paranodal loop suggests that periaxin could be required for the
      adhesion complex. GDAP1 is a relatively common cause of CMT4. Half of reported
      patients showed the demyelinating form, while the rest showed the axonal form.
      The typical feature of CMT4A is paresis of the vocal cords and diaphragm. CMT4B2
      is characterized by autosomal recessive, juvenile onset glaucoma and focally
      folded myelin in sural nerves. SBF2/MTMR13 mutations cause CMT4B2. Early onset
      glaucoma was seen in patients with nonsense mutations. SBF2/MTMR13 and MTMR2,
      which is the cause of CMT4B1, could be acting on the same 3-phosphoinositide
      signaling pathway. Clinical phenotypes of patients with SCAN1 showed cerebellar
      ataxia and axonal neuropathy. TDP1 acts on the single strand break repair
      pathway, and works specifically on topoisomerase I related SSBR. Disruption of
      TDP1 could induce a delay in the transcription process. The low rate of protein
      supply could lead to deaths of large neuronal cell.

PMID- 17432175
TI  - [Clinical and neurological features of organoarsenic compound (diphenylarsinic
      acid) intoxication in Kamisu, Japan].

PMID- 17432176
TI  - [Dopa-responsive dystonia].
AB  - Dopa-responsive dystonia (DRD) is a clinical syndrome characterized by childhood
      onset dystonia and a dramatic and sustained response to relatively low doses of
      levodopa. There are at least three causative genes for DRD: 1) the GCH1 gene on
      chromosome 14q22.1-q22.2, coding for the enzyme GTP cyclohydrolase I (GTPCH) that
      catalyzes the rate-limiting step in the tetrahydrobiopterin (BH4; the cofactor
      for tyrosine hydroxylase [TH]) biosynthesis, 2) the TH gene on 11p15.5, and 3) an
      as yet undefined gene on 14q13 (DYT14). In our series, 86% of families with DRD
      or dystonia with motor delay (an intermediate phenotype between GTPCH-deficient
      DRD [mild] and GTPCH-deficient hyperphenylalaninemia [severe]) had identifiable
      GCH1 or (rarely) TH mutations. Neurochemical data suggest that striatal dopamine
      reduction in GTPCH-deficient DRD (the major form of DRD) is caused not only by
      decreased TH activity resulting from a low cofactor level but also by actual loss
      of TH protein without nerve terminal loss. This TH protein reduction in the
      striatum (especially in the putamen) may be due to a diminished regulatory effect
      of BH4 on stability of TH molecules or to a dysfunction of TH protein transport
      from the substantia nigra to the striatum.

PMID- 17432177
TI  - [Personal recollection of episodes devoted to my study of neuropathology].
AB  - I graduated from Kyoto University Faculty of Medicine in 1952. Following
      neurological residency training, I received neuropathological training at
      Montefiore Hospital under Dr. Zimmerman since 1956. During 1959-65, on the
      recommendation from Dr. Zimmerman and Dr. LT Kurlands, I was engaged in Guam
      project of NIH, as a visiting scientist, investigating ALS and parkinsonism
      dementia complex, endemic fatal neurological disorders among the native Chamorro
      population. In 1965 I was appointed as head of the Division of Neuropathology at
      Montefiore Medical Center. I have been Professor of Pathology at Albert Einstein
      College of Medicine since 1971, Professor in the Dominick Purpura Department of
      Neuroscience at Albert Einstein College of Medicine since 1974, and The Harry M.
      Zimmerman Professor of Neuropathology, Montefiore Medical Center 1995. For over
      four decades, with the late Dr. Zimmerman, I have been host to 40 Japanese
      neurologists who have come to Montefiore for training in Neuropathology. Over 700
      papers, 20 books have been published in our laboratory. Personal recollections of
      selected episodes devoted to study of neuropathology are described in this
      communication. These include fine structural investigation of brain edema
      demonstrating electron dense hematogenous edema fluid spreading expanding
      extracellular space in white matter, application of model of unrolled myelin
      sheath for elucidate structural alteration of myelin, the independent development
      of the pre- and postsynaptic terminals, study of SOD1 positive Lewy body-like
      inclusion in familial ALS and Hirano body.

PMID- 17432178
TI  - [Management of stroke in Korea, now].
AB  - Korea is a rapidly growing aging society and stroke is still the second cause of
      death, comprised of about 15% of the total death in Korea. But the mortality of
      stroke is slightly decreasing despite increase of stroke incidence, probably due
      to improvement of management of stroke and related risk factors. The advent of
      DWI/ MRA enables us to make more accurate patho-etiological diagnoses of ischemic
      strokes. With the findings in DWI/ MRA and the new classification policy that
      entrusts the final judgment to stroke specialists of each hospital, we could
      further classify the large artery disease of the TOAST classification into in
      situ thrombosis, artery to artery embolism, and low-flow infarction and make the
      most plausible diagnosis of undetermined etiology in the TOAST classification. In
      this article we reviewed medical and surgical treatment of stroke, especially
      focusing the clinical practice in Korea. We also provided our results of in vivo
      experiments with promising drugs and stem cells, too. In conclusion, there are
      too many uncertain areas of stroke managements yet to be settled. We need larger
      clinical data pools that are collected based on accurate etiological diagnoses of
      stroke subtypes on the one hand, and brilliant basic research on the other.

PMID- 17432179
TI  - [The neuropathology of sleep in human neurodegenerative diseases].

PMID- 17432180
TI  - [Guideline for the practice of headache].

PMID- 17432181
TI  - [Neuroimaging in mild cognitive impairment].
AB  - I summarized the present status of Neuroimaging studies in mild cognitive
      impairment (MCI). Nation wide multi-center study with regard to single photon
      emission study had been started 3 year before and it is now going on in a good
      cooperation of many institute, covering 319 cases. This study was name as J
      COSMIC (Japan Cooperative SPECT Study on Assessment of Mild Impairment of
      Cognitive Function). After one-year follow-up, 30 out of 120 cases were converted
      to Alzheimer's disease from MCI. Since last year, ADNI (Alzheimer' disease
      Neuroimaging Initiative) had started in US, very similar to J-COSMIC, but they
      adopted PET and MRI as the examination tool. The findings based on J-COSMIC is
      still unclear, but, we can say that the general cognitive evaluation methods such
      as MMSE is better than WMS-R, which measures the memory function itself with wide
      variation in each case. Similar to small size previous works, converter from MCI
      to Alzheimer's disease tended to show hypoperfusion in the parietal and frontal
      regions. Recent advance in the molecular imaging enabled us to visualize the
      deposition of amyloid protein in the brain parenchyma. It is still controversial
      as to application of the early diagnosis of Alzheimer's disease or MCI. S.
      Minoshima reported the hypometabolism in the early stage of Alzheimer's disease
      in the posterior cingulate gyrus or precuneus, but it has been still unknown why
      these areas showed hypoperfusion or hypometabolism in early phase of Alzheimer's
      disease. We examined the fiber connection of posterior cingulate region with
      other brain structures using diffusion weighted images. It was very surprising
      that such kind of small structures had a lot of connections, not only
      contralateral side, but also, parietal and temporal lobes, as well as anterior
      cigulate cortex. The function has been still been unclear, but we will be able to
      disclose their functions in the human brain in the future, which will be helpful
      for understanding the pathophysiological changes in MCI.

PMID- 17432182
TI  - [Cell sheet engineering].
AB  - Cell sheets can be prepared by culturing cells at 37 degrees C on temperature
      responsive surfaces, modified with poly (N-isopropylacrylamide) at a thickness of
      20-30 nm. Cultured cell sheets are successfully harvested and manipulated by
      simple temperature changes from 37 degrees C to 20 degrees C due to
      hydrophobic/hydrophilic changes of the dish surfaces. This technology has led to
      "cell sheet engineering" which has initiated new therapies for tissue engineering
      and regenerative medicine. Various cell sheets such as corneal epithelium,
      corneal endothelium, skin, periodontal ligaments, oral mucosal epithelium,
      urothelium, and cardiomyocyte tissues have already been fabricating using these
      temperature-responsive cell culture surfaces. Additionally, we have already
      initiated clinical treatments using both corneal and oral mucosal epithelial cell
      sheets for the treatment of patients with corneal surface diseases. By creating
      layered cell sheets, structural and functional connections can be achieved.
      Therefore, we have successfully prepared synchronously beating heart tissues in
      vitro. Finally, we are also examining the use of heterogeneously layered cell
      sheets to create laminar structures that resemble the functional and structural
      units of complex organs such as the liver and kidney.

PMID- 17432183
TI  - [Echocardiography in stroke patients (with emphasis on cryptogenic stroke)].
AB  - As discussed throughout this review, multiple potential cardioembolic sources for
      stroke can be identified with the use of echocardiography. We believe that
      echocardiography plays an important role in the evaluation and risk
      stratification of patients with suspected cardioembolic stroke and, when used
      appropriately, can help in the management and treatment of these patients.
      Although TTE is superior for evaluation for the presence of a mural thrombus, TEE
      offers a higher sensitivity and specificity in identifying nearly all other
      potential cardiac sources of stroke. In the patient in whom the clinical scenario
      appears to implicate the heart as a potential culprit in an embolic event, the
      threshold for evaluation with echocardiography should be low.

PMID- 17432184
TI  - [Cellular mechanisms of protein quality control].

PMID- 17432185
TI  - [Postgraduate training program of neurology in Tokyo Medical and Dental
      University].
AB  - The trainee physicians who joined our group start their training of Neurology 3rd
      or 4th years after the graduation. The 1st goal is to pass the board exam of
      internal medicine and then the board exam of neurology. The neurology training
      course is operated in the University and affiliated hospitals in a combined
      manner for 3 to 4 years because the training period require at least 3 years for
      the internal medicine and 6 years for the neurology exams. During the training in
      the University, there are 3 full-time training periods for neurophysiology,
      neuroradiology and neuropathology. Each training period is 2 to 3 months.
      Clinical neurology is trained mainly in ward as a member of a team composed of an
      assistant professor, a trainee physician (resident), a junior resident and a
      student. Around the neurology board exam, those interested in research enter the
      Graduate School and study for Ph.D. In these 10 years, many members of our
      department have become professors in neurology, rehabilitation and basic
      medicine, directors in research institutes, owners or practitioners of clinics,
      and so on. We will continue to provide a top-level training of neurology
      following our mission that we contribute peoples' happiness through neurology.

PMID- 17432186
TI  - [Intelligent operating theater].
AB  - The intelligent operating theater (IOT) is an operating room where it provided
      with "Advanced hands, vision and brain for Surgeon". Improvement of the surgical
      outcome of malignant brain tumor surgery requires a better anticipation of the
      surgical procedure and patient's anatomical and functional environment of the
      region of interest (ROI). Localization of functional areas in the brain also
      differs among patients, and excess removal of tumor near eloquent areas may
      increase the risk of damage to function, such as motor paresis and speech
      disturbance. Recent progress in magnetic resonance (MR) imaging technology which
      enabled to acquire intraoperative images totally changed the neurosurgery of
      malignant brain tumor. Since intraoperative MR images (iMRI) visualize the size
      of residual tumor and the positional relationship between the tumor and eloquent
      areas, surgeons can achieve safe and reliable surgery. The IOT with iMRI has a
      role to assist the surgeon's decision for next surgical procedures by showing the
      present status real-timely. In order to compensate the deformation and shift of
      the organ due to surgical procedures preoperative images are not sufficient and
      it is necessary to up-date the navigation information using intraoperatively
      acquired images. These surgical support using intraoperative images are a must to
      accomplish the safe and accurate surgery.

PMID- 17432187
TI  - [Historical review on the researches on muscular dystrophies].

PMID- 17432188
TI  - [Brain and sleep mechanism].
AB  - It is now accepted that sleep is induced by biological clock located in the
      suprachiasmatic nucleus and/or sleep promoting substances, which influence
      ventrolateral preoptic (VLPO) neurons. The VLPO neurons affects more caudally
      situated posterior hypothalamic ones containing orexine and/or histamine,
      reciprocally. When these neurons inhibit lower brainstem aminergic ones, sleep is
      induced. REM (Rapid Eye Movement) sleep can be induced mainly by brainstem
      cholinergic neurons, when aminergic ones are completely inhibited. During this
      stage, tonic activities and phasic Ponto-Geniculate-Occipital (PGO) ones
      originated within brainstem cholinergic neurons activate irregularly many parts
      of the brain such as the cerebral cortex and limbic system to produce dream-like
      activity. Muscle atonia is also observed during REM sleep. This atonia is caused
      by neurons in the pontine reticular inhibitory area (PIA), which is normally
      inhibited by aminergic inputs. The PIA affects medullary neurons of the
      paramedian and/or magnocelullar nuclei to regulate motoneurons in the ventral
      horn. Therefore. muscle atonia is produced when these PPT cells are active during
      REM sleep. In addition, based upon many recent data, sleep is not a passive state
      but rather an active state, during which recuperation of neuronal system is
      promoted and information processing is executed.

PMID- 17432189
TI  - [Electrodiagnosis of ALS].
AB  - Electrodiagnostic methods are crucial for the diagnosis of ALS. In nerve
      conduction studies, normal sensory conduction and absence of the sign of
      demyelination is required. Here, false-positive signs for demyelination should be
      paid special attention. Loss of motor units in ALS alone can cause significant
      slowing and absence of F-waves. Needle electromyography shows active neurogenic
      changes with denervation potentials (fibrillation potentials and positive sharp
      waves) and polyphasic and unstable motor unit potentials (MUPs). High-amplitude
      or giant MUPs may not be evident in rapidly progressing cases. Complex repetitive
      discharges are frequently seen. World Federation of Neurology established
      criteria for the diagnosis of ALS at El Escorial workshop in 1994, which was
      later revised (Airlie House criteria; AHC, 1998). The problem of AHC is its low
      sensitivity, especially in early cases. Specificity should also be cautioned
      because widespread fibrillations and frequent high-amplitude MUPs in chronic
      myopathies, such as inclusion body myositis, may easily fulfil the
      electrodiagnostic criteria in AHC. The diagnostic value of fasciculation
      potentials (FPs) is devaluated in AHC because of its "low specificity". However,
      our investigation using EMG database actually revealed high specificity of FPs
      for ALS, which may be a key point in considering the pathophysiology of ALS.

PMID- 17432190
TI  - [Amyotrophic lateral sclerosis with dementia (ALSD)].
AB  - Patients with ALSD show characteristic mental and behavioral changes, represented
      by lack of insight into their tragic condition. Psychiatric symptoms usually
      precede life-threatening motor neuron symptoms. Cerebral SPECT, especially 3D
      SSP, exercises its power in the diagnosis of ALSD by demonstrating constant and
      sharp blood flow reduction in the prefrontal region. The neuropathology of the
      cerebral cortex is characterized by most prominent and probably earliest
      degeneration in the medial side cortex of the temporal pole, border zone between
      the CA1 and subiculum, ambient gyrus, and amygdala as well as cytoplasmic
      ubiquitinated inclusion bodies in the dentate gyrus granular neurons and other
      cortical small neurons. Motoneuron pathology is almost the same as that in
      classic ALS except for more prominent Bunina bodies and less affected pyramidal
      tract. The substantia nigra is usually degenerated without Lewy bodies. A
      condition recently proposed as motor neuron disease-inclusion dementia seems to
      be a forme froste of ALSD. Several cases of ALSD exhibited upper motor neuron
      dominant involvement, showing the possibility that the category of ALSD may be
      widened than considered so far.

PMID- 17432191
TI  - [Phenotypic variation in ALS].
AB  - Making a diagnosis of typical amyotrophic lateral sclerosis (ALS) is not a tough
      job, but when it comes to atypical forms of motor neuron disease (MND) which are
      not uncommon in clinical setting, we may have some difficulty to diagnose
      ALS/MND. There is striking phenotypic variation in sporadic ALS/MND, such as
      frail arm syndrome (brachial amyotrophic diplegia), pseudopolyneuritic form,
      hemiplegic type, ALS/MND with markedly extended involvement beyond the motor
      system, and MND with basophilic inclusion bodies. These variations must be
      recognized if physicians are to tailor advice on disease progression, prognosis,
      drug therapy, and care to the needs of the individual. Clinical trials of new
      therapeutic agents have been performed, on the assumption that patients with
      ALS/MND have the same underlying etiology, addressing the heterogeneous
      population of the patients under a single diagnostic category. This can be
      detrimental to the well-being of the individual, because clinical heterogeneity
      may mask drug effects in clinical trials. The attempt to categorize subgroups
      based on the clinical and pathological backgrounds within the spectrum of ALS/MND
      may be a critical step in facilitating clinical research in ALS/MND. Definition
      of clinicopathologic syndromes in patients with ALS/MND is an important
      challenging task that cannot be ignored.

PMID- 17432192
TI  - [Management and care for patients with ALS].
AB  - For the past decade or so, the research in ALS has dramatically changed,
      coinciding with the discovery of SOD1 mutations, the generation of SOD1
      transgenic rodents, and the introduction of riluzole. The ALS practice guidelines
      have been published in a number of countries, whereas the National Database has
      shown the actual reality of patient practice in ALS. Multidisciplinary ALS
      Clinics, consisting of a team of health care professionals, provide highly
      specialized quality care for patients and families, and have become the standard
      of care in many countries. A number of mostly retrospective studies report that
      non-invasive positive pressure ventilation prolongs survival and improves the
      quality of life and other functions. Enteral feeding certainly improves quality
      of life, but it is still uncertain if it prolongs survival. Although end of life
      issues in ALS care have been difficult more and more ALS clinicians are paying
      serious attention to it. Clinical trials are imperative to find effective
      medications for ALS, and many different pharmacological agents, based on a number
      of different hypotheses in ALS, are being actively tested or are about to be
      tested in the near future. Undoubtedly, we are in the midst of incredible
      progress in ALS.

PMID- 17432193
TI  - [Role of neurologists on the management of stroke care unit and/or stroke unit].
AB  - Intravenous thrombolytic therapy for acute ischemic stroke with recombinant
      tissue plasminogen activator was approved to be under the application of Japanese
      health insurance on October 2005. To practice the high-quality therapy in stroke
      care unit and/or stroke unit, neurologist should play the role of a team leader
      and coordinator, working together with various medical staffs. The next
      neurologist in generation should have the mission and the passion for realizing
      the assured stroke center in all parts of country and seriously manage hyper
      acute stroke patients in strained situation.

PMID- 17432194
TI  - [Early detection of ischemic lesions in the super-acute phase of ischemic
      cerebrovascular diseases by imaging].
AB  - A thrombolytic agent, recombinant tissue plasminogen activator (rt-PA), was
      recently approved in Japan for use on patients within 3 hrs of the onset of
      cerebral infarction. In order to salvage cerebral tissue after an ischemic
      insult, it is crucial to detect the ischemic lesion before it becomes
      irreversible and to detect the core and penumbra areas of the lesion for guidance
      in selecting the suitable therapy. In this symposium we discuss the detection of
      ischemic lesions using plain CT, perfusion CT, and MRI. In the section on plain
      CT, we present a typical case with early CT signs. In the section on perfusion
      CT, we report on the feasibility and limitation of the technique for the
      diagnosis of acute cerebral infarction. In the section on MRI, we study the
      usefulness of DWI for the early and highly reliable detection of ischemic stroke.

PMID- 17432195
TI  - [Thrombolytic therapy].
AB  - Favorable outcome by hyperacute rt-PA (recombinant tissue-type plasminogen
      activator) therapy was suggested firstly by randomized controlled trials (RCT) in
      Japan, and confirmed by the NINDS trial (1995) using alteplase within the initial
      3 hours. A phase III clinical trial using open-labeled, single-dose alteplase was
      carried out in Japan (Japan Alteplase Clinical Trial, J-ACT). The study protocol
      was almost compatible to that of the NINDS study, except for several
      modifications including lower dose administration of alteplase (0.6 mg/kg) in the
      J-ACT than that in the NINDS study (0.9 mg/kg). The clinical backgrounds were
      almost similar, and frequencies of very favorable outcome at 3-months and
      symptomatic intracranial hemorrhage were comparable between the studies. The
      Japanese Government approved the use of intravenous alteplase therapy in October
      11, 2005. The Japan Stroke Society published a guideline and gave more than 130
      courses for appropriate alteplase therapy immediately after the approval.
      Clinical results of this therapy were excellent in the initial 21 cases of our
      hospital. New approaches will open the door to an exciting new era for stroke
      management. They include MR-based delayed thrombolysis up to 9 hours after stroke
      onset and ultrasound-enhanced systemic thrombolysis.

PMID- 17432196
TI  - [Antithrombotic therapy in acute ischemic stroke].
AB  - The purpose of antithrombotic therapy is not to recanalyze obstruction but to
      prevent propagation of thrombus and reocclusion by rethrombosis in the brain
      arteries. There is no evidence of heparin or heparinoid to improve long-term
      outcome, although anticoagulant therapy might be indicated for stroke associated
      with coagulation activation such as progressing stroke, basilar artery
      thrombosis, cardioembolic stroke at high risk, coagulopathy, and arterial
      dissection. In patients with nonvalvular atrial fibrillation, there is no
      evidence of immediate anticoagulation with heparin to improve long-term outcome,
      which is rather contraindicated for large hemispheric stroke, and it is
      recommended to start warfarin directly in the safety issue. Aspirin is
      recommended in the guidelines of many countries, although the efficacy is modest.
      A clinical trial of the GP IIb/IIIa inhibitor abciximab, which is a more potent
      antiplatelet agent than aspirin, had recently been conducted, although it was
      stopped because of the concern on the safety. Clinical trials of dual
      antiplatelet therapy with aspirin and another antiplatelet agent are ongoing to
      compare efficacy and safety with aspirin monotherapy in Japan and overseas.

PMID- 17432197
TI  - [Language gene].
AB  - The human capacity for acquiring speech and language must derive, at least in
      part, from the genome. Recent advance in the field of molecular genetics finally
      discovered 'Language Gene'. Disruption of FOXP2 gene, the firstly identified
      'language gene' causes severe speech and language disorder. To elucidate the
      anatomical basis of language processing in the brain, we examined the expression
      pattern of FOXP2/Foxp2 genes in the monkey and rat brains through development. We
      found the preferential expression of FOXP2/Foxp2 in the striosomal compartment of
      the developing striatum. Thus, we suggest the striatum, particularly striosomal
      system may participate in neural information processing for language and speech.
      Our suggestion is consistent with the declarative/ procedural model of language
      proposed by Ullman (1997, 2001), which the procedural memory-dependent mental
      grammar is rooted in the basal ganglia and the frontal cortex, and the
      declarative memory-dependent mental lexicon is rooted in the temporal lobe.

PMID- 17432199
TI  - [The uniqueness of human language].

PMID- 17432198
TI  - [Biological significance of Broca's region].
AB  - Since P. Broca (France) reported in 1960's the case with disturbance of speech
      caused by the left infero-posterior frontal lesion, this region was considered to
      be a kineticism speech center (Broca's area: BA). Linguistic functions have been
      clarified afterwards by many studies and case reports. Doubt whether the former
      BA where Homo Sapiens got a linguistic functions would take any kind of function
      is left as expected. We have faced an original function of BA based on results
      provided accidentally in our studies related to sensori-motor linkage mechanisms.
      Then, we have clarified brain function about non-linguistic processing. BA and
      the primary motor area (M1) were activated approximately at the same level, when
      a subject observed and performed the same actions by herself as ones of another
      person. In case that she imitated actions of another person, activities of BA and
      M1 increased significantly (Human Mirror Neuron System: HMNS). Subjects with
      Asperger's syndrome are impaired in social interaction and imitation of action
      showed abnormal processing of HMNS in BA and M1 which could account for a part of
      imitation and social impairments. These results converge on a central role of
      Broca's area as an orchestrator of time sensitive perceptual and motor functions
      underlying and non-verbally social communication.

PMID- 17432200
TI  - [Neural mechanisms of syntax].
AB  - Agrammatism is defined as a disorder of language expression, characterized by the
      omission of the relational words: articles, prepositions, conjunctions, and minor
      modifiers. The resulting output is generally referred to as nonfluent aphasia.
      Disorder of syntactic comprehension is also observed and we have implemented a
      binary decision task for a clinical investigation. However, this task could not
      make clear how and why a patient made errors. Hence we used here the object
      manipulation task, which patients manipulated some animal toys to depict the
      sentence they heard, for patients with infarcts in BA44, 45/46. Stimulus
      sentences contained several sentence patterns, including scrambled sentences
      grammatically possible in Japanese but ungrammatical in English. Results were as
      follows: i) All patients could not understand scrambled active sentences.
      Additionally, complex sentences for BA44, and three-place verb sentences for
      BA45/46, were difficult to understand. ii) Unlike English/French patients,
      Japanese patients could depict passive sentences easily rather than three-place
      verb sentences (BA45/46). iii) All patients made common errors: selecting another
      item; default strategy; simplifying sentence construction. Considering these
      results and recent studies, we speculate that syntax reflects rules to
      segmentalize (or categorize) the external world to process sensorimotor
      information effectively for thinking and communication.

PMID- 17432201
TI  - [Epidemiology of multiple sclerosis in Japanese: with special reference to
      opticopsinal multiple sclerosis].
AB  - The fourth nationwide survey of multiple sclerosis (MS) disclosed that the
      estimated number of MS patients in Japan was 9,900, and the estimated prevalence
      rate of MS is 7.7 per 100,000, indicating that the number of MS patients has been
      rapidly increasing for the past 30 years. The demographic features of the present
      series were compared with those of the three past nationwide surveys. The ratio
      of female to male patients has increased from 1.3 to 2.9. As to distribution of
      age at onset, in 2004, the peak of the age at onset curve shifted from the 30s to
      20s and the second peak at 50s seen in the 1989 survey disappeared this time.
      About 60% were conventional MS (CMS) while 20% were opticospinal MS (OSMS) plus
      optic-brainstem-spinal MS (OBSMS). The female to male ratio was significantly
      greater in OSMS than in CMS, and age at onset was also significantly higher in
      OSMS than in CMS in both male and female. By distribution of age at onset, CMS
      showed a single peak in the early 20s while OSMS showed the highest peak in the
      early 20s and a second peak in the 30s. Both visual impairment at onset and
      severe visual impairment during the course have decreased to about half of those
      found in the first survey, while frequencies of both quadriparesis and transverse
      myelitis considerably decreased in 2004 compared to 1989 in addition to a
      decrease of visual impairment. Disease progression was significantly faster with
      advancing age at onset. In respect to the McDonald criteria, dissemination in
      space was fulfilled in 45.5% in CMS while only in 8.2% in OSMS patients. Spinal
      cord lesions were found in more than 90% of OSMS and 70% of CMS patients.
      Longitudinally extensive spinal cord lesions extending over 3 vertebral segments
      were detected in 41.2% of OSMS and 16.7% of CMS patients. In conclusion, the
      fourth nationwide survey disclosed significant changes in the prevalence and
      demographic features of MS in the Japanese population.

PMID- 17432202
TI  - [What are the unique characteristics of optico-spinal MS in Japanese and
      neuromyelitis optica in western populations].
AB  - Although the diagnosis of optico-spinal MS (OSMS) is solely based on the unique
      lesion distribution, the OSMS is clinically characterized by distinctive features
      which are mostly shared by the clinical characteristics of relapsing
      neuromyelitis optica (NMO). Conversely, Western investigators appear to consider
      relapsing NMO as a distinct entity from MS, and distinct characteristics and
      independent diagnostic criteria for NMO were proposed. However, the key
      characteristics of OSMS and NMO seem to be quite similar, and therefore the
      prototype of these disorders are identical which we would like to call OSMS/NMO.
      Most of the described characteristics of the OSMS/NMO appear to reflect the
      fulminant nature of each attack and the expansion of each lesion, which we called
      "attack-related severity". Recently, we found that clinical characteristics seem
      to be distinctively different between OSMS patients with and without
      longitudinally extending spinal cord lesions while clinical features of OSMS
      patients without extending spinal cord lesions are similar to those of CMS
      patients. To understand the pathomechanisms of OSMS and NMO, the "attack-related
      severity" must be an important key factor as well as the unique lesion
      distribution.

PMID- 17432203
TI  - [Laboratory findings in optic-spinal multiple sclerosis].
AB  - Optic-spinal multiple sclerosis (OSMS) is characterized by the selective and
      severe involvement of the optic nerves and spinal cord. Typical OSMS is similar
      to neuromyelitis optica (NMO) in many respects. NMO has distinct laboratory
      findings from those in classical MS, which are important to understand the unique
      pathogenesis of NMO. In the cerebrospinal fluid (CSF) examination, oligoclonal
      IgG bands are negative, and IgG1% is not elevated in NMO. Both Th1- and Th2
      associated chemokines are altered in the CSF of NMO as well as classical MS.
      Neurofilament heavy chain levels in the CSF are elevated in NMO, but not in
      classical MS, suggesting severer axonal damage in NMO. Unique neuropathological
      findings in NMO include tissue necrosis, gray matter involvement, and
      perivascular deposition of immunoglobulins and complements. NMO-IgG is a disease
      specific autoantibody for NMO. Complete blindness and longitudinally extensive (>
      3 vertebral segments) myelitis are commonly seen in NMO-IgG-positive cases. Some
      NMO-IgG-positive patients develop such brain lesions as hypothalamic, periaque
      ductal, and bilateral extensive ones, and they appear to be different from
      typical lesions of classical MS. A recent multi-center study in Japanese OSMS has
      revealed that OSMS is classified into two subtypes, 1) NMO and 2) MS with optic
      spinal presentation.

PMID- 17432204
TI  - [Treatment].

PMID- 17432205
TI  - [Autonomic neuropathy in type-2 diabetes, lessons from Okamoto Diabetes Study].
AB  - Clinically important diabetic autonomic neuropathy includes constipation,
      diarrhea, neurogenic bladder, impotence, dry skin, arterio-venous shunt in the
      lower extremities, reduced heart rate variability with tachycardia, orthostatic
      hypotension, and dysautoregulation of the cerebral blood flow. To investigate the
      prevalence, clinical characteristics and risk factor for diabetic complications,
      prospective epidemiological study (Okamoto Diabetes Study) has been started since
      1991. Autonomic neuropathy was judged from the results of RR interval variation
      (CV < or = 1.5) and/or orthostatic change of systolic blood pressure (deltaSBP >
      or = 30 mmHg). The prevalence of autonomic neuropathy was 28% in type-2 diabetes
      enrolled in the Okamoto Diabetes Study. Aging, duration of diabetes, higher
      systolic blood pressure and HbA1c levels were independent risk factors for
      autonomic neuropathy. Frequent association with macrovascular complications in
      the subjects with autonomic neuropathy resulted in poor prognosis, especially due
      to cardiovascular events. The 55 subjects (19% of the 286 subjects already died)
      had died suddenly. Cause of sudden death in these subjects is still unclear, but
      silent myocardial infarction due to autonomic neuropathy may be, at least in
      part, one of the major causes of unexpected sudden death in type-2 diabetes.

PMID- 17432206
TI  - [Autonomic dysfunction in FAP: its therapeutic effect by liver transplantation].
AB  - FAP is characterized by progressive polyneuropathy and autonomic dysfunction and
      the latter consists of marked orthostatic hypotension, disturbed bowel movement,
      impotence and urinary incontinence. All these autonomic symptoms severely affect
      patient's daily activity. The precursor protein of amyloid fibrils in this
      disease is a variant form of transthyretin (TTR) in serum. Since TTR is produced
      mainly in the liver, liver transplantation has been employed for FAP patients as
      only one curative treatment. During the past 12 years more than 50 FAP patients
      underwent liver transplantation in Japan and the five-year survival rate of them
      was 77%. Early intervention (less than 5 years after onset) can provide a better
      chance of improving patients' condition after transplantation and
      gastrointestinal autonomic symptoms that include severe episodic nausea,
      vomiting, and alternating constipation and diarrhea significantly relieve shortly
      after operation. Preoperative clinical severity and the nutritional status of
      patients are correlated with their outcome after liver transplantation. Among
      them the presence of an autonomic failure in FAP patients seems to be
      contraindication for this challenging operation.

PMID- 17432207
TI  - [Autonomic involvement in Guillain-Barre syndrome].
AB  - Guillain-Barre syndrome (GBS) is an acute self-limited motor-dominant neuropathy,
      in which autonomic nervous system is frequently involved. Cardiovascular
      complications, such as hypertension, hypotension, bradyarrhythmias, and
      tachyarrythmias, are particularly important because they are sometimes life
      threatening. Antiganglioside antibodies are frequently present in the acute-phase
      sera of GBS. They are considered to be useful for diagnosis and to be involved in
      the pathogenetic mechanisms. No association between autonomic dysfunction and
      antiganglioside antibody however has been reported. Recently, we performed the
      quantitative sudomotor axon reflex test (QSART) in GBS patients and found that
      patients with high scores in QSART had anti-GQ1b IgG antibodies. It indicates the
      association between postganglionic sudomotor dysfunction and anti-GQ1b
      antibodies. Further investigation on larger number of patients is needed to
      clarify the role of antiganglioside antibodies in the development of autonomic
      dysfunction.

PMID- 17432208
TI  - [Autonomic function tests for analysis of pathophysiology and prognosis of
      autonomic neuropathy].
AB  - It is recommended to assess each autonomic system with system-specific function
      tests. Pupillary and cardiocirculatory systems have a benefit to perform the
      tests quantitatively, but most of the other systems are measured qualitatively.
      The aim of the tests exist in detecting the focus and the severity of a disease.
      Some tests are favored to be used repeatedly for judging the recovery. Head-up
      tilt and Valsalva tests are not adequate to observe the short-term improvement,
      but serum noradrenalin level has a good correlation to the rapid recovery.
      Autonomic symptoms may occur due to the dysfunction not by the efferent
      sympathetic pathway but by the afferent in rare cases. Sympathetic overactive
      conditions can be observed in those situations.

PMID- 17432209
TI  - [The role of autophagy in quality control inside neural cells].
AB  - Autophagy is an intracellular, bulk degradation process, through which a portion
      of cytoplasm is delivered to lysosomes to be degraded. In many organisms, the
      primary role of autophagy is adaptation to starvation. However, we have found
      that autophagy is also important for intracellular quality control, particularly
      in quiescent cells such as neurons. Atg5 -/- mice die shortly after birth due, at
      least in part, to nutrient deficiency. These mice also exhibit an intracellular
      accumulation of protein aggregates in neurons and hepatocytes. Neural cell
      specific Atg5-deficient mice, Atg5(flox/flox); Nestin-Cre mice, show progressive
      deficits in motor function and degeneration of some neural cells. In autophagy
      deficient cells, diffuse accumulation of abnormal proteins occurs, followed by
      generation of aggregates and inclusions. This study emphasizes that basal
      autophagy is important even in individuals who do not express neurodegenerative
      disease-associated mutant proteins. Further, the primary targets of autophagy are
      diffused cytosolic proteins, not protein aggregates themselves. These data
      suggest that basal autophagy has a critical role in intracellular protein quality
      control under normal conditions, which is independent of the role of induced
      autophagy as an adaptation to starvation.

PMID- 17432210
TI  - [Neurodegenerative disease and autophagy].
AB  - In neurodegenerative diseases, accumulation of aggregated proteins leads to
      inclusion body formation which is the hallmark of the pathological findings.
      Formation of inclusion bodies is now thought to be a cellular protective
      mechanism to collect aggregated proteins to a small compartment in the cell since
      more oligomeric form of aggregated proteins seem to have more toxicity than
      highly polymeric aggregates which are present in the inclusion bodies. The
      experimental inclusion body called aggresome is formed at microtubule organizing
      center by the help of microtubules and motor protein complex upon proteasome
      inhibition. Recently, the author reported that the collection of aggregated
      proteins to aggresome is closely related to their degradation by autophagy
      lysosomal degradation system which strongly suggested that autophagy is a back-up
      system for ubiquitin proteasomal protein degradation system. Thus to find ways to
      upregulate protein degradation system including ubiquitin proteasome system and
      autophagy for therapeutic point of view is a quite promising strategy.

PMID- 17432211
TI  - [Neurodegenerative diseases regulated by ubiquitin-proteasome system].
AB  - Various inherited neurodegenerative diseases result from an increase in the
      number of glutamine codon repeats within the open reading frame of the
      responsible gene. Insoluble aggregates of polyglutamine-containing proteins in
      neurons, which are usually conjugated with ubiquitin, are a hallmark of the
      polyglutamine diseases. However, the molecular mechanism underlying the
      ubiquitylation and aggregate formation of polyglutamine-containing proteins has
      been largely unclear. Here we report the identification of critical factors
      involved in the ubiquitylation process as well as turnover of MJD1/Ataxin-3
      protein, in which the abnormal expansion of a polyglutamine tract is responsible
      for spinocerebellar ataxia type 3 (SCA3, also known as Machado-Joseph disease).
      E4 B/UFD2a (a ubiquitin chain assembly factor) and VCP (a AAA-family ATPase) were
      co-purified with the activity polyubiquitylating Ataxin-3. E4B mediated
      polyubiquitylation of MJD1/Ataxin-3, and VCP interacted with both E 4B and MJD1
      Ataxin-3. In a Drosophila model of SCA3, expression of E4B suppressed the
      neurodegeneration induced by an Ataxin-3 mutant. These observations suggest that
      E4 is a rate-limiting factor in the degradation of proteins with expanded
      polyglutamine tracts.

PMID- 17432212
TI  - [Lewy bodies: neuroprotective?].

PMID- 17432213
TI  - [Intravascular malignant lymphomatosis (IML) as a cause of cryptogenic stroke].
AB  - IML as one of the causes of cryptogenic stroke was nevieued in terms of the
      clinical features, diagnosis and treatment of IML. IML is a rare type of lymphoma
      which primarily proliferates inside blood vessels, caused mostly by B-cell type
      lymphocytes and rarely by T-cell type lymphocytes. IML has been difficult to be
      diagnosed antemortem because of nonspecific clinical and laboratory
      abnormalities, and has carried a poor prognosis. However, recent observations
      show that systemic chemotherapy may improve the outcome of IML in some patients,
      so that it is important to diagnose IML early and to initiate its treatment. We
      should consider the possibility of IML, if patients showed one or any combination
      of the following progressive four neurological features of undetermined etiology:
      1) subacute multifocal cerebral infarcts, 2) paraparesis, 3) subacute
      encephalopathy, and 4) mononeuropathy to multiple mononeuropathy, particularly if
      patients showed an elevation of serum LDH and soluble interleukin-2R values,
      albuminocytologic dissociation in the cerebrospinal fluid, or any of the 3
      abnormalities. If the possibility of IML is present, we should perform biopsies
      in involved areas such as skin, skeletal muscle and brain. Recent reports also
      show that polymerase chain reaction test of B-type lymphocytes in the peripheral
      blood is also helpful, involving the immunoglobulin heavy chain gene variable
      region. Early diagnosis and early treatment by vigorous chemotherapy such as
      biweekly CHOP therapy may improve the outcome of IML.

PMID- 17432214
TI  - [Migraine and stroke].
AB  - Both migraine and stroke are common illness. However, each disorder usually
      occurs in different generation, migraine in younger, while stroke in elder, and
      seems to have little in common. Migraine has been supposed to be benign, not life
      threatening illness occurring throughout the life-time. Whereas, stroke is an
      acute illness with certain degree of disabilities consequently, even fatal in
      case. In spite of such differences, some of recent studies suggested migraine as
      a risk factor of stroke or subclinical brain damage. There seems to be several
      types of stroke associated with migraine. One is "migrainous infarction", which
      is defined as one or more migrainous aura symptoms associated with an ischemic
      brain lesion in appropriate territory demonstrated neuroimaging, in the
      International Classification of Headache Disorders (ICHD-II). The other is stroke
      occurring in those who had been suffering from migraine in their younger time.
      The former is seldom to observe, and the latter is in dispute. Recent elaborate
      epidemiological studies disclosed the risk of stroke is increase in people with
      migraine, particularly marked in those with migraine with aura, further increased
      in those taking oral contraceptives. However, several issues such as strict
      diagnostic criteria for stroke and migraine, history of medication for migraine
      treatment, etc. for those studies should be settled. The well organized
      prospective studies for the issue "migraine as a risk factor of stroke" should be
      considered necessary.

PMID- 17432215
TI  - [Thrombotic microangiopathy].
AB  - Thrombotic microangiopathies (TMAs) are characterized by thrombocytopenia,
      microangiopathic hemolytic anemia, and organ failure (mostly renal dysfunction).
      TMA includes thrombotic thrombocytopenic purpura (TTP) with predominant
      neurological signs and hemolytic uremic syndrome (HUS) with predominant renal
      dysfunction, but they are often indistinguishable each other with the clinical
      signs alone. Recent availability of von Willebrand factor-cleaving protease or
      ADAMTS13 activity has defined that TTP is a syndrome frequently associated with a
      deficient ADAMTS13 activity with or without its inhibitors (autoantibodies),
      whereas HUS has almost the normal activity. Here, we present two cases of TMA,
      who were initially diagnosed as "multiple sclerosis" because of the fluctuated
      neurological signs. Case 1 was a 54-year-old male and case 2 was a 30-year-old
      female. During their clinical course, they accompanied thrombocytopenia, to which
      the etiology left undetermined in case 1, but case 2 was suspected DIC because
      she had such past history. Prophylactic infusion of platelet concentrates to both
      cases dramatically aggravated their clinical signs. Case 1 was diagnosed to be
      intravascular lymphoma complicated with acquired TTP, after showing a deficient
      ADAMTS13 activity. Case 2 was unable to assay ADAMTS13 activity, but later the
      autopsy revealed the presence of multiple hyaline membrane thrombosis in many
      organs, together with a lack of demyelinating lesions, solely confirming a
      diagnosis of TMA.

PMID- 17432216
TI  - [Drug abuse and stroke].
AB  - Today, drug abuse pervade all over the world. Drug abusers are increasing year
      after year also in recent Japan especially among young people. Ischemic and
      hemorrhagic stroke frequently occur after use of illegal drugs. We reported two
      cases of young stroke associated with drug misuse. Case 1 used amphetamine,
      cocaine, marijuana and LSD for few yaers, and developed occlusion of a middle
      cerebral artery. Case 2 presented aphasia shortly after marijuana smoking. His
      protein S activity was low. He did not have other risk factor of cerebrovascular
      disease. Marijuana may have accelerated stroke onset, but essential cause of
      stroke in this case must be protein S mutation. Medical examination for young
      stroke should include screening of drug abuse and searching for coagulation
      disorder.

PMID- 17432217
TI  - [Reading and writing Japanese: Kanji versus Kana].
AB  - In my talk, I reviewed studies on the neural substrates of Kanji vs. Kana, two
      types of Japanese characters, written since the 1980s. More Specifically, I
      reviewed the development of the studies on (1) Kanji and Kana in pure
      alexia/agraphia, (2) alexia with agraphia of Kanji and (3) 'musical letters' vs.
      'literary letters', and reported new findings from those studies. In the 1980s,
      we frequently studied patients with partial callosal lesions and those with pure
      alexia, and many of the studies were on the neural substrates of Kanji vs. Kana.
      Later, we discovered cases of alexia with agraphia of Kanji caused by lesions in
      the posterior part of the left inferior temporal gyrus, leading us to understand
      the neural substrates of Kanji and Kana in more detail. In addition to the
      reading and writing of 'literary letters', we studied the neural mechanisms of
      the reading and writing of 'musical letters', i.e. musical scores. Our study
      showed that the neural mechanisms of reading and writing musical scores were
      similar to those of reading and writing 'literary letters' in professional
      musicians, although those neural mechanisms varied slightly.

PMID- 17432218
TI  - [Neuroscience of cursive handwriting: a computational appraoch].
AB  - Based on the minimum torque change model (MTCM), Wada and Kawato (1995) proposed
      a computational model of cursive handwriting which includes the following
      assumptions. The brain represents via-points that the hand passes through in a
      trajectory. Cursive handwriting consists of consecutive reaching movements. The
      via-points for handwriting are retrieved from memory during actual handwriting.
      Mathematically extracted via-points based on MTCM proved to be practically
      identical to motor primitives measured by EMG suggesting that drastic directional
      changes in muscle movement may be determining the location of via-points. Based
      on computational model, we examined the via-points in the cursive handwriting of
      a patient with parietal lobe involvement accompaning agraphia. While the control
      subject showed basically the same numbers and locations in via-points regardless
      of the velocity of hand movement, the patient's number and locations of via
      points differed depending on the velocity of hand movement. The results suggest
      that the control subject retrieved necessary via-points based on the velocity of
      handwriting. The results also may reflect the neuropsychological nature of
      agraphic hand writing in a patient with parietal lobe damage.

PMID- 17432219
TI  - [Neural mechanism of reading].
AB  - We conducted positron emission tomography studies on reading and found that two
      distinct areas were activated, i.e. the left fusiform/inferior temporal gyri
      (posterior inferior temporal cortex, Area 37) by kanji words and the
      fusiform/inferior occipital gyri (posterior occipital gyri, Area 18/19) by kana
      words. Clinically, alexia and agraphia for kanji is caused by a posterior
      inferior temporal cortex lesion. Moreover, pure alexia more impaired for kanji
      results from a fusiform gyrus lesion, whereas pure alexia for kana occurs because
      of damage to the posterior occipital gyri. These experimental and clinical
      findings suggest that impaired letter identification in Area 18/ 19 causes pure
      alexia for kana, disrupted visual images of words in Area 37 results in alexia
      with agraphia for kanji, and impaired access to the visual image storage (Area
      37) yields pure alexia dominantly disturbed for kanji.

PMID- 17432220
TI  - [Mechanisms of writing].
AB  - Writing impairments are caused by various different mechanisms and lesions. The
      left posterior inferior temporal lobe plays the important role in retrieving the
      morphograms of the characters. Therefore the lesions involving this region have
      more effect on Kanji (Japanese morphogram) than on Kana (Japanese phonogram). The
      angular gyrus is considered to maintain the retrieved letter/character
      information and convert the naive information into writing performance. Sometimes
      Kana dominant impairment is detected due to this lesion because in some persons
      may have the direct route from phonemic presentation into writing execution
      process without definite retrieval of its form or morphology. The left superior
      parietal lobule is associated to the writing execution, thus, the lesion in this
      region induces the impairment of writing stroke and ill-shaped characters. The
      posterior part of the left middle frontal gyrus is related to select and arrange
      the letters to make a word, so the lesion in this area will develop paragraphia,
      in particular replacement of the letters within a word. Recently, the typing of
      the keyboard is becoming more popular in our everyday life. Reflecting this
      phenomenon, specific typing impairment called dystypia is reported. It is
      supposed that there is the impairment between linguistic process and typing
      execution.

PMID- 17432221
TI  - [Beta- and gamma-secretases].
AB  - Deposition of amyloid beta peptides (Abeta) as amyloid deposits characterizes the
      brains of patients with Alzheimer's disease (AD). Mutations in presenilin genes
      linked to familial AD (FAD) have been shown to increase production of Abeta42, an
      initially and predominantly depositing Abeta species in all types of AD. PS has
      been shown to serve as the catalytic center for the gamma-secretase cleavage of a
      subset of single-pass membrane proteins including beta-amyloid precursor protein
      and Notch. gamma-Secretase inhibitors, including gamma42-selective inhibitors
      like NSAIDs, are emerging therapeutic agents for AD. Also, an establishment of a
      method to monitor the progression of AD using imaging and biochemical surrogate
      markers would be vital to the evaluation of the effects of disease-modifying
      drugs for AD. In this regard, a large-scale observation study, like the AD
      neuroimaging initiative (ADNI), should be conducted in Japan.

PMID- 17432222
TI  - [Vaccination--update].

PMID- 17432223
TI  - [Animal models of tauopathies].
AB  - Accumulation of intraneuronal amyloid comprised of tau proteins occurs in a group
      of neurodegenerative disorders, collectively termed tauopathies, and pathological
      alterations of tau proteins alone are sufficient to cause degeneration of
      neurons, as compellingly evidenced by discovery of tau gene mutations in kindreds
      of familial tauopathy known as frontotemporal dementia with parkinsonism linked
      to chromosome 17 (FTDP-17). Mice modeling tauopathies have been generated by
      overexpression of human tau with FTDP-17 mutations, in order to gain more
      profound insights into molecular links between tau abnormalities and
      neurodegeneration. A subset of these mice were reported to exhibit abundant tau
      amyloid lesions resembling neurofibrillary changes in human tauopathies, and
      pronounced neuronal loss notable as progressive brain atrophy. Significantly,
      formation of mature amyloid fibrils is not tightly associated with neuron death,
      while deposition of microtubule-unbound phosphorylated tau, which conceivably
      emerges early in tau fibrillogenesis, appears to critically contribute to
      disruption of neuronal integrity. In addition to such mechanistic elucidation,
      mouse models of tauopathies are currently being applied to exploitation of
      imaging agents for visualization of tau pathologies in living brains. This
      technology would greatly facilitate diagnostic workup of patients with suspected
      tauopathies when combined with appropriate imaging modalities.

PMID- 17432224
TI  - [From neuropathology to biomarker development in Alzheimer research].
AB  - Recent advances in our understanding of neurobiology of Alzheimer's disease (AD)
      demonstrate that AD starts with accumulation of amyloid beta-protein (Abeta)
      followed by abnormal phosphorylation of tau protein and a massive neuron death in
      vulnerable brain areas. We have shown that cerebrospinal fluid tau and
      phosphorylated tau are elevated in subjects with mild cognitive impairment, the
      earliest detectable clinical stage of dementia and AD, suggesting that the
      pathogenic cascade of AD may arrive at the stage that finally leads to an
      accumulation of abnormally phosphorylated tau in the MCI stage. These results may
      highlight the need to develop another diagnostic tool that reliably monitors and
      visualize brain beta-amyloid burden in living subjects who are at increased risk
      of developing AD. We assume that the detection of asymptomatic stage of AD
      followed by an early intervention may lead to maximum therapeutic benefits. In an
      attempt to accomplish this goal, we have generated several novel chemicals that
      specifically bind to Abeta peptide upon entry into mouse brain. The "amyloid
      imaging" seems closest to ideal biomarker if safely and successfully applied in
      humans because this non-invasive technique can also monitor treatment outcome
      following anti-Abeta therapy.

PMID- 17432225
TI  - [Treatment of Duchenne muscular dystrophy by induction of skipping of dystrophi
      exon].

PMID- 17432226
TI  - [Specific inhibition of nonsense-mediated mRNA decay has the potential to rescue
      the phenotype of muscular dystrophy].
AB  - Nonsense-mediated mRNA decay (NMD) is an mRNA quality-control mechanism that
      degrades aberrant mRNAs containing premature translation termination codons
      (PTCs). The essential proteins for NMD include SMG-1, a protein kinase, and Upf,
      a substrate of SMG-1 with RNA helicase activity. In this study, we evaluated the
      effect of NMD inhibition on the phenotype of Ullrich disease, an autosomal
      recessive congenital muscular dystrophy, by pharmacological inhibition of SMG-1
      or siRNA-mediated knockdown of SMG-1 or Upf1. The patient studied, showed a
      homozygous frame-shift mutation with a PTC in the collagen VI alpha2 gene, which
      encodes a truncated but partially functional protein. The patient's fibroblasts
      showed a nearly complete loss of the triple-helical collagen VI protein and
      functional defects in the extracellular matrix (ECM) due to the crucial
      deficiency of the collagen VI alpha2 protein. We have shown that NMD inhibition
      causes the up-regulation of the mutant collagen VI a2 subunit, resulting in the
      assembly of mutant triple-helical collagen VI and the formation of partially
      functional ECM. The results suggest that specific inhibition of NMD may be useful
      as a therapeutic approach to treat some human genetic diseases exacerbated by
      NMD.

PMID- 17432227
TI  - [Therapeutic strategies for muscular dystrophy by myostatin inhibition].
AB  - Myostatin is a member of the TGF-beta superfamily that is expressed predominantly
      in skeletal muscle and functions as a negative regulator of skeletal muscle mass.
      Myostatin inhibition, therefore, has tremendous potential for increasing muscle
      mass clinically to treat patients with muscle wasting diseases. Systemic
      administration of a myostatin neutralizing antibody in mdx mice (a model of
      Duchenne muscular dystrophy) resulted in an increase in skeletal muscle mass and
      strength. A human anti-myostatin monoclonal antibody, MYO-029 is under clinical
      trials in patients with muscular dystrophy in the USA and Europe. Additional
      approaches to myostatin inhibition have been shown to have beneficial effects in
      vivo. Blockade of myostatin activity with the myostatin prodomain resulted in
      increases in muscle mass, enhanced muscle function, and histological improvement
      of the dystrophic muscle in mdx mice and mutant caveolin-3 transgenic mice (a
      model of LGMD1C). Treatment with an extracellular ligand-binding domain of the
      myostatin receptor, ActRIIB, resulted in prominent muscle mass increases in
      LGMD1C model mice. These findings indicate that myostatin inhibition could lead
      to effective therapeutics to treat muscular dystrophy. However, therapeutic
      indication against various types of muscular dystrophy as well as safety of the
      treatment should be established for the future clinical application.

PMID- 17432228
TI  - [Stem cell based cell therapy for muscular dystrophy].
AB  - Stem cell-based cell therapy is one of attractive therapeutic approaches to
      muscular dystrophy. In transplantation into dystrophic skeletal muscle, muscle
      satellite cells and musclE side population (SP) cells are good candidates as
      sources of stem cells. We purified mouse satellite cells from adult C57B16 mice
      by FACS using a monoclonal antibody, SM/C-2.6, which can specifically recognize
      quiescent satellite cells. DNA micro-array analysis on both quiescent and
      activated satellite cells allowed us to distinguish novel quiescent satellite
      cell-specific genes. These genes may encode molecules that keep satellite cells
      in a dormant and undifferentiated state. We transplanted purified muscle
      satellite cells transduced with lentivirus vector, and found these cells were
      effectively incorporated into dystrophin-deficient skeletal muscle and expressed
      transduced dystrophin. We also identified a novel side population (SP) cells in
      uninjured and regenerating skeletal muscle. The majority of muscle-SP cells in
      uninjured stage showed endothelial cell-like properties. CD31 negative/CD45
      negative SP cells were a minor population in normal conditions, but actively
      proliferate during muscle regeneration. Co-transplantation experiments showed
      that the SP cells synergistically promoted muscle regeneration with satellite
      cells. It is indispensable to study molecular basis of muscle stem cells and
      muscle regeneration to achieve effective stem cell-based cell therapy on muscular
      dystrophy.

PMID- 17432229
TI  - [Trends in the management of herpes simplex encephalitis].
AB  - Recent aspects of the diagnostic and therapeutic management of herpes simplex
      virus encephalitis (HSVE) are reviewed based on a clinical analysis of our adult
      patients. Detection of the HSV genome sequence in the cerebrospinal fluid (CSF)
      by the polymerase chain reaction (PCR) has been established as a gold standard
      diagnostic method at the acute stage of HSVE. However, several problems for the
      PCR in HSVE remain, as follows: the discrepancy in results based on differences
      of minimum detection sensitivities between the single PCR and nested PCR, and
      clinical pseudo-negative results which depend on the day of CSF sample collection
      after onset. Antiviral therapy is highly effective in reducing the mortality
      rate. However, only less than one-half of HSVE patients are able to return to
      normal. This finding indicates a need to develop a further improved therapeutic
      regimen. We recently reported an assessment of the efficacy of corticosteroid
      with aciclovir therapy for outcome in HSVE using multiple logistic regression
      analysis. A poor outcome was evident with older age, lower Glasgow Coma Scale
      scores at initiation of aciclovir, and no administration of corticosteroid.
      Combination therapy employing both aciclovir and corticosteroid is thus suggested
      to be useful for achieving a better outcome.

PMID- 17432230
TI  - [HHV-6 encephalitis following allogeneic hematopoietic cell transplantation].

PMID- 17432231
TI  - [Japanese guidelines for the management of herpes simplex encephalitis;
      comparison with those from the International Management Herpes Forum].
AB  - Herpes simplex encephalitis (HSE) is still recognized as a severe sporadic
      encephalitis, although the mortality and morbidity rates have been decreased to
      10% and 30%, respectively. This disease is diagnosed using clinical symptoms,
      CSF, EEG, CT, MRI, and virologic tests such as polymerase chain reaction (PCR) or
      enzyme immunosorbent assay (EIA). Early diagnosis and treatment are essential for
      HSE. However, the early symptoms of this disease are various, and the laboratory
      diagnostic criteria are unclear to the non-specialist. In 2005, Japanese
      guidelines for the management of HSE have been issued via two sets of Workshops
      at the Japanese Neuroinfectious Disease Congress. The diagnostic and therapeutic
      criteria were discussed in comparison with those from the International
      Management Herpes Forum (IMHF) in 2004. For a definitive diagnosis, CSF PCR for
      herpes simplex virus (HSV) is recommended, and the detection rate has been
      reported to be 60 to 80% within the 7th day of the illness. In the IMHF, the PCR
      method has also been the primary method for early diagnosis and for monitoring
      the therapy. Further, quantitative real-time PCR has become available for
      measuring the effectiveness of aciclovir therapy. To measure HSV antibody levels,
      complement antibody (CF), neutralizing antibody (NT), or enzyme-linked
      immunosorbent assay (ELISA or EIA) are available. Significant elevation of EIA
      IgG or intrathecal HSV antibody production should be shown, although these
      antibody responses often appear two weeks after the onset of HSE. Regarding anti
      herpesvirus drugs, in both Japanese and IMHF guidelines aciclovir is consistent
      with the first choice, and it is recommended that its administration would be
      started as soon as HSE is suspected on the basis of clinical pictures, CT * MRI,
      EEG, or CSF findings. However, antiviral therapy may be discontinued if a
      negative CSF HSV PCR is obtained at > 72 hours after onset. A recent Japanese
      study shows the efficacy of a combination therapy of aciclovir and corticosteroid
      for this disease. Further prospective investigation is expected.

PMID- 17432232
TI  - [Herpes simplex encephalitis in childhood].
AB  - Central nervous system (CNS) infection by herpes simplex virus (HSV) in childhood
      consists of herpes simplex encephalitis and CNS infections in neonates. Herpes
      simplex encephalitis in children resembles that in adults, but CNS infections in
      neonates differs from adult herpes simplex encephalitis in pathogenesis and
      clinical features. Trans-neuronal transmission by HSV type 1 causes herpes
      simplex encephalitis both in children and adults, while hematogeneous spread by
      HSV type 1 or type 2 causes CNS infections in neonates. Mortality of CNS
      infections by HSV in childhood has been improved since early diagnosis by
      polymerase chain reaction and anti-viral therapies have been established.
      However, neurological morbidity has not yet been improved and sometimes HSV
      infections relapse after the acyclovir therapy. Recently, longer acyclovir
      therapy with larger doses is recommended for the treatment of CNS infections in
      childhood.

PMID- 17432233
TI  - [Dystonia update].

PMID- 17432234
TI  - [A pathomechanism for the genesis of dystonia: striatal compartments and
      hypothesized model of basal ganglia circuits].
AB  - X-linked recessive dystonia-parkinsonism (XDP; DYT3; Lubag) is an adult-onset
      disorder that manifests severe and progressive dystonia with a high frequency of
      generalization. In search for the anatomical basis for dystonia, we performed
      postmortem analyses of the functional anatomy of the basal ganglia based on the
      striatal compartments (i.e., the striosomes and matrix compartment) in XDP. Our
      study showed that in the XDP neostriatum, the matrix compartment is relatively
      spared in a mosaic pattern, whereas the striosomes are severely depleted. In view
      of the three-pathway basal ganglia model, we postulate that the disproportionate
      involvement of neostriatal compartments and their efferent projections may
      underlie the manifestation of dystonia in patients with XDP. This study is the
      first to show specific basal ganglia pathology that could explain the genesis of
      dystonia in human heredodegenerative movement disorders, suggesting that dystonia
      may result from an imbalance in the activity between the striosomal and matrix
      pathways.

PMID- 17432235
TI  - [Current status and prospects of medical therapy for dystonia].
AB  - The goal of medical therapy for primary dystonia is conservative. While botulinum
      toxin (BTX) therapy is a first choice for blepharospasm and cervical dystonia,
      medical therapy is selected as such for other types of dystonia. As oral
      medications, trihexyphenidyl and benzodiazepines are most frequently used. Muscle
      relaxants are also commonly used, but dopamine antagonists are not recommended
      because of the risk of inducing tardive dyskinesia. For childhood-onset
      generalized dystonia, levodopa should be considered to rule out levodopa
      responsive dystonia. Mexiletine is reported to be effective not only for
      bleharospasm and cervical dystonia but for focal limb dystonia. To improve the
      therapeutic performance of BTX therapy for blepharospasm, it is recommended that
      corrugator supercilii and procerus muscles, as well as orbicularis oculi muscle,
      be added as target muscles. To improve the therapeutic performance of BTX therapy
      for cervical dystonia, it is recommended that this therapy be started as early as
      possible, especially within one year of illness, and that levator scapulae muscle
      be added as target if necessary. To improve usefulness of medical therapy for
      dystonia, its strategy must be standardized, and more useful therapies must be
      positively adopted. Algorithm for treatment of dystonia must also be established
      and generalized.

PMID- 17432236
TI  - [Neurosurgical management of dystonias].
AB  - Dystonia is not a rare condition and there are more than 10 patients per 100,000
      general population. In recent years various neurosurgical interventions have been
      proven to be effective for various types of dystonias. For example, generalized
      dystonia involving whole the body and resulting in bed-ridden state can be
      dramatically improved with stereotactic chronic deep brain stimulation of the
      globus pallidum interna. Cervical dystonia is the most common among dystonias and
      exhibits symptoms of spasmodic torticollis. The first treatment of choice is
      local injection of botulinum toxin. But if the symptoms are refractory to the
      conservative treatment, selective peripheral denervation of the involved muscles
      is a well-established safe and effective surgical method. Task-specific focal
      hand dystonia, often called as writer's cramp, is no longer a psychogenic
      condition. Ventrooralis thalamotomy interrupting the oscillatory hyperactive
      cortico-pallido-thalamic circuit results in excellent relief of the symptom. of
      writer's cramp. Thus, in the modern era of functional neurosurgery, we
      neurosurgeons should regard most dystonias as a definite neurosurgical condition.
      In this review, we describe the current state of neurosurgical treatment for
      dystonias.

PMID- 17432237
TI  - New challenges in trichinellosis control.

PMID- 17432238
TI  - [Biology, species biodiversity and distribution of Trichinella nematodes].
AB  - From the time of the discovery of Trichinella larvae in 1835 until the middle of
      the next century it was commonly assumed that all trichinellosis was caused by a
      single species Trichinella spiralis. This species is an intracellular parasite in
      both a larva and an adult stage. The L1 larvae live in a modified skeletal
      muscles. The adult worms occupy a membrane-bound portion of columnar epitelium,
      living as intramulticellular parasite. More than century later T. spiralis have
      been reported from more than 150 different naturally or experimentally infected
      hosts and demonstrated worldwide distribution in domestic and/or sylvatic
      animals. Up to date, Trichinella genus comprised eight species (T. spiralis, T.
      nativa, T. britovi, T. murrelli, T. nelsoni, T. pseudospiralis, T. papuae and T.
      zimbabwensisi) and three additional genotypic variants that have not yet to be
      taxonomically defined (T6, T8, T9). Molecular markers revealed that Trichinella
      T6 is related to T. nativa, Trichinella T8 related to T. britovi. Two main clades
      are recognized in the genus Trichinella: the first encapsulated in host muscle
      tissue and the second--non-encapsulated. In this paper the history of Trichinella
      spp. discovery, their life cycle, taxonomy and phylogeny have been reviewed.

PMID- 17432239
TI  - [Methods and tools for parasite differentiation within the genus Trichinella].
AB  - This review summarizes the major biological, biochemical and molecular methods
      which have been developed during last 20 years to distinguish parasites of the
      genus Trichinella. From the time of the discovery of Trichinella in 1835 until
      the 1970, it was assumed that trichinellosis was caused by a single species of
      parasite, Trichinella spiralis. Many biological parameters have been compared to
      differentiate the parasite, such as host specificity, geographical distribution,
      reproductive abilities, nurse cell development and resistance to freezing. Now,
      investigators realize that the genus Trichinella is a much more complex group of
      parasites and simple biological methods are non sufficient. In order to identify
      and better characterize the species and genotypes of Trichinella it was necessary
      to develop more sensitive techniques. First, for detecting Trichinella infection
      immunological methods have been used, such as detection of antibodies in host
      blood and antigens of parasites using monoclonal antibodies against
      immunodominant proteins. Later, biochemical techniques have been used such as
      isoenzyme analysis. The main goal of these methods is to provide a simple, rapid
      and reproducible techniques to differentiate Trichinella parasites. For this
      purpose DNA-based methods appeared the best ones. Beginning with the use
      restriction enzymes, repetitive DNA probes for detection of parasite DNA, and
      later techniques based on the polymerase chain reaction (PCR), give results at
      the high level of sensitivity. All of this information has been used to construct
      a new taxonomy of the genus Thrichinella. To date, 11 taxa have been recognized
      in the genus: 8 species (Trichinella spiralis T1, Trichinella nativa T2,
      Trichinella britovi T3, Trichinella pseudospiralis T4, Trichinella murrelli T5,
      Trichinella nelsoni T7, Trichinella papuae T10, Trichinella zimbabwensis T 11)
      and additionally three genotypes whose taxonomic status is yet uncertain (T6, T8,
      T9). Based upon morphology, epidemiology of trichinellosis, geographical
      distribution and host range of the parasite, two main groups are recognized in
      the genus Trichinella. The first group comprises species that encapsulate in host
      muscle tissue, while the species of the second group do not encapsulate. The
      species and genotypes of the first group infect only mammals (T. spiralis, T.
      nativa, T. britovi, T. murrelli, T. nelsoni, T6, T8 and T9), whereas of the three
      species from the second group, one parasitizes mammals and birds (T.
      pseudospiralis) and the other two infect mammals and reptiles (T. papuae and T.
      zimbabwensis). Due to the big genetic differences between Trichinella isolates,
      investigators predict that the number of species and genotypes found within
      Trichinella will be increased.

PMID- 17432240
TI  - [Wild and domestic animals as permanent Trichinella reservoir in Poland].
AB  - BACKGROUND: [corrected] Since Owen first described Trichinella as a human patogen
      in 1835, the number of organisms comprising this genus has grown dramatically.
      This etiological agent of human trichinellosis shows worldwide distribution in
      domestic and/or sylvatic animals. MATERIAL AND METHOD: The aim of the presented
      paper was to determine the distribution of Trichinella species in wild animals
      such as red foxes, wolves, wild boars, and domestic pigs in Poland. Muscle
      samples from diaphragm and forelegs were collected from animals killed by
      hunters. Muscle larvae were recovered from the muscle after artificial digestion
      and identified at the species level by RAPD, PCR-RPLF and multiplex PCR. RESULTS:
      Of 75 nematode isolates from red foxes: (Vulpes vulpes), 50 resulted as T.
      britovi, 6 T. spiralis, 6 were mixed infections of these two species. Fifteen
      Trichinella isolates remained unidentified. Of 97 nematode isolates from wild
      boars (Sus scrofa), 21 resulted as T. britovi, 69 T. spiralis, 2 were mixed
      infections of these two species. Five Trichinella isolates remained unidentified.
      Of 6 examined wolves (Canis lupus) killed in the Bieszczady region, 3 animals
      were positive against T. britovi. Of 6 examined raccon dogs (Nyctereutes
      procyonoides) from Pomorskie region, 2 animals were positive against T. spiralis.
      Of 21 nematode isolates from domestic pigs, 1 resulted as T. britovi and 21 as T.
      spiralis. Up to date, two Trichinella species are detected as the etiological
      agents of epidemiology among domestic and wildlife animal in Poland: T. britovi
      is the dominant species in red foxes and T. spiralis is the dominant species in
      wild boars and domestic pigs.

PMID- 17432241
TI  - [Epidemiology of human trichinellosis in Poland--currently and in the past].
AB  - Since the XIX century human trichinellosis has remained an unsolved problem of
      public healthcare in Poland. This paper describes the past situation and analyses
      current changes in the epidemiological pattern of trichinellosis in Poland.
      Epidemiological data from the last 60 years, point out that the number of human
      cases as well as the number of deaths caused by trichinellosis has decreased
      significantly. Up to 90s the main source of Trichinella infection for people was
      pork. Among other implemented control measures, the introduction of the
      artificial digestion method in the early 80s to detect trichinellosis in pigs
      resulted in a shift in the sources of Trichinella infection in humans - pork was
      replaced with wild boar meat. In the years 1990-1995 the number of outbreaks due
      to pork consumption was 3.5-times higher than in the years 2000-2005. In the
      early nineties pork was the source of infection causing about 71% of all
      outbreaks; in 2000-2005 that number has fallen to only 12%. On the other hand
      wild boar meat was responsible for 23% of the outbreaks in 1990-1995 and as many
      as 88% of all outbreaks in the years 2000-2005. Moreover the number of persons
      infected in the outbreaks significantly decreased. The study of wild animals
      demonstrated that wild boars in Poland are infected not only with T. spiralis but
      also with Trichinella britovi. These results and EU recommendations indicate a
      requirement of determining the Trichinella species which cause infections in
      outbreaks. In the 3 trichinellosis outbreaks in 2005 the infected meat products
      were examined with molecular tools. T. spiralis species larvae were the
      etiological agents of infection in all these outbreaks. The current
      epidemiological situation of trichinellosis in Poland indicates a need of
      increasing the awareness of risks related to wild boar meat consumption among the
      general public. Introducing the artificial digestion method as an obligatory
      method for wild boar meat examination is also necessary.

PMID- 17432242
TI  - [A selected aspects of clinical pathology of human trichinellosis].
AB  - In this review the pathomechanisms of human trichinellosis with particular
      relation to intestinal and muscular invasion are presented. The numerous factors
      initiated by antigen released by Trichinella, which play a role in the
      development of pathological process (including immunological, pathomorphological,
      metabolic and bioelectric disturbances) and short clinical characteristics of the
      disease are also presented. Pathology of late period of trichninellosis sequelae
      are discussed.

PMID- 17432243
TI  - [Evaluation of the meat carcases assigned for consumption towards the presence of
      Trichinella larvae by two methods: trichinoscopy and digestion].
AB  - The main purpose of this article was to analyse the effectiveness of two methods:
      trichinoscopy and digestion method for control of animal trichinellosis. It was
      established that the using of magnetic stirrer improved the digestion of meat and
      shortened the digestion to 90-100 minutes. It is worthy of notice that the
      digestion method is three to four times more sensitive than the traditional
      trichinoscopy. In the years 1999-2004 Trichinella larvae were found in pork meat
      6 times rarely comparing with the years 1990-1994. The introduction of digestion
      method resulted directly in the reduction (4 times) of the Trichinella infection
      in humans in the years 2000-2004 comparing with the years 1990-1994. The ELISA
      test appeared to be also very useful for epidemiological studies on Trichinella
      infection in animals and humans.

PMID- 17432244
TI  - [The usefulness of ELISA for diagnosis of trichinellosis in pigs and wild boars].
AB  - ELISA can be used to measure produced antibodies or Trichinella spp. antigens in
      the samples. They are detected with antibodies linked to an enzyme that reacts
      with a substrate and generate a colour reaction. The optical density (OD) of the
      reaction is measured spectrophotometrically. ELISA assays can be done in several
      different procedures called "direct", "indirect", "sa ndwich", and "competition"
      ELISA. Since the 1970s, the studies have been done on improving or replacing
      direct methods of Trichinella diagnosis with serological methods based on the
      ELISA. When somatic antigens of L1 T. spiralis were used, the specificity of the
      ELISA was poor due to a high probability of cross-reactions with other pathogens.
      During the 1980s the specificity of the ELISA was improved by excretory-secretory
      (E/S) antigens obtained during Trichinella muscle larvae incubation in vitro.
      Recently a synthetic glycan antigen has been developed and the increasing of
      ELISA specificity and sensitivity was noticed. The sensitivity of the ELISA using
      an E/S antigen ranging from 93.1 to 99.2% but the specificity from 90.6 to 99.4%.
      The ELISA method is relatively simple to apply, reliable, readily standardized
      and provides an acceptable balance of sensitivity and specificity. But all
      modified procedures should be validated. In Poland, the studies on the usefulness
      of ELISA for antibodies detection against T. spiralis in pigs and wild animals
      are limited. Own ELISA procedure was prepared in Pathophysiology Lab. in W.
      Stefanski Institute of Parasitology of PAS. ELISA was used to examine IgG level
      against L1 T. spiralis in pigs and wild boars serum samples. Of 1474 pig samples,
      only 12 were positive. Of 1880 wild boar samples only 14 were positive. The
      results of this study are comparable with performance obtained using commercial
      sets. The results showed the usefulness of ELISA for T. spiralis diagnosis in
      pigs and wild boars and confirmed the possibility of use the ELISA test for
      application in the slaughterhouse.

PMID- 17432246
TI  - [The influence of the procedure of excretory-secretory L1 trichinella spiralis
      antigen preparation on the efficiency of an ELISA test in pigs].
AB  - BACKGROUND: Trichinellosis is a parasitic zoonosis transmitted to humans by
      consumption of raw or undercooked meat from animals infected by worms of the
      Trichinella genus. Every year seropositive cases are found among the human
      population and thus trichinellosis still remains an epidemiologically important
      disease in Poland. The usefulness of ELISA for anti-T. spiralis IgG detection in
      pigs is still limited by the nature of antigen. The objective in the present
      study was to compare the usefulness of excretory-secretory antigens of L1 T.
      spiralis for the serological detection of IgG antibodies in pigs. MATERIAL AND
      METHODS: The antigens were prepared in different laboratories: Ag ES L1 T.
      spiralis (N) in Germany, Ag ES L1 T. spiralis (W) in Italy and Ag ES L1 T.
      spiralis in Poland. Conventional, Iberian pigs were infected with 200, 1000 and
      20 000 muscle larvae of T. spiralis. Serum samples were obtained at 5 and 1 dbi
      (day before infection), and 5, 10, 15, 20, 25, 30, 40, 50, 60 dpi (day post
      infection) and screened for specific IgG antibodies to excretory-secretory L1 T.
      spiralis antigens. Serum samples were obtained from the EU project TRICHIPORSE.
      The cut-off value of ELISA was determined on serum samples from 248 Trichinella
      free pigs from Poznaii and Boza Wola, that were examined by artificial digestion.
      RESULTS: In pigs infected with 200 L1 T. spiralis larvae, specific IgG were
      detectable from 50 dpi, when the Ag ES L1 T. spiralis (N) was used, whereas when
      Ag ES L1 T. spiralis (W) and Ag ES L1 T. spiralis were used, the specific IgG
      were detectable from 40 dpi. In pigs infected with 1000 LI T. spiralis larvae,
      specific IgG was observed from 30 dpi when Ag ES L1 T. spiralis (W) and Ag ES L1
      T. spiralis were used, but when Ag ES L1 T. spiralis (N) was used specific IgG
      were detectable from 40 dpi. In the group infected with the highest dose of T.
      spiralis larvae, specific IgG were detectable from 30 dpi when Ag ES L1 T.
      spiralis (N) and Ag ES L1 T. spiralis (W) were used, whereas when Ag ES L1 T.
      spiralis was used specific IgG were detectable from 20 dpi. The results strongly
      indicated that in the examined pigs, the specific IgG response against T.
      spiralis infection is dose dependent. Furthermore, it was shown that the high
      infectious dose induced earlier increasing of specific IgG response. Statistical
      analysis revealed a significant positive correlation between OD values obtained
      in procedures based on the three antigens. The results were statistically
      repeatable for procedures and for single pigs (P<0.01).

PMID- 17432245
TI  - Analysis of the epidemiological factors influencing vulpine trichinellosis in
      ecologically different regions of Slovakia.
AB  - INTRODUCTION: In the Slovak Republic, trichinellosis circulates almost
      exclusively in the sylvatic cycle, with main reservoir host red fox and wild boar
      and sporadic occurrence of human outbreaks. A detailed study was performed in
      five ecologically different regions of eastern Slovakia with more profound regard
      to eco-geographical and anthropogenic influences to natural fox habitat. MATERIAL
      AND METHODS: In total of 689 red foxes (Vulpes vulpes) hunted in selected regions
      in 2005/2006 was examined using artificial digestion method. Larvae obtained from
      infected samples were on the species level characterised using multiplex PCR
      analysis. RESULTS: The study revealed a total prevalence of 15.6%, with most
      frequent occurrence of infected foxes in the mountain of the Volovske Vrchy
      (25.2%) where both human habitation and fox population are very dense. High
      prevalence rates were found in the Kosicka Kotlina Basin (19.6%) with urbanised
      landscape, concentrated human activities and low fox population and in national
      park of the High Tatras (15.8%) where the inhabitants and fox population are
      relatively low. In the remote localities of the Nizke Beskydy Highlands that
      represent ideal fox habitat free of any human impact, 14.2% of foxes harboured
      Trichinella larvae. The lowest occurrence of infected foxes (6.9%) was found in
      agrarian areas of the Vychodoslovenska Nizina Lowland, with relatively low
      inhabitants and fox population density. In all localities Trichinella britovi was
      the most important etiological agent of sylvatic trichinellosis.

PMID- 17432247
TI  - The estimation of different ELISA procedures for serodiagnosis of human
      trichinellosis.
AB  - INTRODUCTION: The most important confirmative diagnostic test for trichinellosis
      is the presence of the muscle larvae in a tissue biopsy but this direct method
      has a low sensitivity of light and moderate infections. The aim of presented
      study was to compare the usefulness of the results obtained by three ELISA
      procedures for Trichinella spp. diagnosis in human outbreaks. MATERIALS AND
      METHODS: All sera (cases and controls) were tested for anti-Trichinella
      antibodies (immunoglobulin G) using commercially available Novatec KIT and two
      other ELISA procedures based on excretory-secretory (ES) antigens on Trichinella
      spiralis muscle larvae. The main differences in ELISA procedures were: the
      protein concentration in antigen, dilution of human serum samples, conjugate and
      the time of conjugate incubation. Additional differences were noticed in ES
      antigen preparation procedures as well as in T. spiralis isolates used in these
      procedures. Serum samples were obtained from 22 symptomatical patients from
      Poznafi region (West Poland), geographic area where human outbreak had occurred.
      Control serum samples were obtained from 20 patients from an open population from
      a non endemic trichinellosis area. RESULTS: The results were analyzed in terms of
      both: statistical and epidemiological point of view. Linear regression analysis
      and correlations coefficient r between OD values of total 22 patients obtained in
      three ELISA procedures were positive and high statistically significant. Three
      ELISA procedures revealed different cut-off values and positivity rates for
      outbreak. However, the majority of positive samples were found as positive in
      three procedures, but some of them were positive in two or one procedure only.
      These individual variability in sera reactivity observed in three ELISA
      procedures could be very important from epidemiological point of view.

PMID- 17432248
TI  - [Influence of free radicals on Trichinella spiralis infection in mice].
AB  - The aim of the study was to examine the influence of free radicals: nitric oxide
      (NO), hydrogen peroxide (H202) and superoxide anion (O2-) on Trichinella spiralis
      infection in mice. The studies were performed on two strains of mice: C57BL/6 and
      BALB/c, which differ in immunological response to T. spiralis infection. Also the
      influence of AG--inhibitor of inducible nitric oxide synthase (iNOS) administered
      in the first days after T. spiralis infection (1-5 dpi) on the cytotoxic immune
      response and on the number of adult parasites as well as the influence of AG
      administered at the beginning of muscle phase of the T. spiralis infection (16-29
      dpi) on the cytotoxic immune response and the number of muscle larvae was
      studied. Activation of macrophages can cause pathology. Contact of macrophages
      with antigens stimulates these cells to produce, among others, highly reactive
      inorganic compounds. There are free radicals: NO, H2O2 and O2-. NO, O2-, and
      their metabolites are highly toxic for most pathogens, including parasites.
      However, little is known about their role in the defense against T. spiralis
      infection. The performed studies have proved, that free radicals play role in the
      host immune response during both intestinal and muscle phase of T. spiralis
      infection in mice. In the intestinal phase of the T. spiralis infection cytotoxic
      immune response is activated in mice peritoneal cavity and in the muscle phase,
      the local immune response activated in the neighborhood of larvae in muscles
      appeared as the higher level of free radicals in blood and urine. Administration
      of AG between 1-5 dpi causes opposite reactions in two different strains of mice.
      In BALB/c mice AG causes fast expulsion of adult T. spiralis from the intestine
      but in C57BL/6 mice the expulsion of parasites is slower after AG. However, there
      are no differences between two strains of mice after treatment with AG between 16
      and 29 dpi. AG causes diminution of larvae in muscles of both BALB/c and C57BL/6
      mice. Inflammatory response in peritoneal cavity is observed later during the
      infection in "low responders" (C57BL/6) mice in comparison with "high responders"
      (BALB/c) mice. Thl like mice (C57BL/6) react stronger to AG treatment than Th2
      like mice (BALB/c). It occurs as changes and fluctuations in free radicals levels
      and the number of peritoneal cells after AG treatment in C57BL/6 mice. Weak or no
      reaction on AG injections in BALB/c mice is responsible for more stabile and more
      sufficient defense response of the host to T. spiralis infection.

PMID- 17432249
TI  - Budget backlash. Disparate forces in healthcare unite to decry Bush's healthcare
      budget for 2008; 'a remarkable leap backward to the stone age'.
AB  - Healthcare lobbyists representing different and, sometimes, conflicting interest
      groups all have an issue to rail against: President Bush's proposed $2.9 trillion
      budget, which would take huge chunks out of some federal healthcare programs.
      Officials like Leslie Norwalk, right, the CMS' acting administrator, support the
      $700 billion of that proposed budget that would fund Medicare and Medicaid.

PMID- 17432250
TI  - Buyouts? That may be all, folks. Proposed Triad deal likely last LBO--for time
      being.

PMID- 17432251
TI  - IRS affirms board accountability. Not-for-profits are warned not to take rules
      lightly.

PMID- 17432252
TI  - Not enough information. Critics say SEIU/Wal-Mart plan lacks specifics.

PMID- 17432253
TI  - Ascension emits tension. In-works Boston system deal has mayor concerned.

PMID- 17432254
TI  - Not another one. New commission meets criticism.

PMID- 17432255
TI  - Putting off the tough choices. As a long-term fiscal crisis worsens, Washington
      dithers.

PMID- 17432256
TI  - Reform beyond access. A plan to extend Medicare model that would also limit
      costs, improve quality.

PMID- 17432257
TI  - Trustees of the Year 2007. Becoming transparent. Schubart brings spirit of
      openness on board at system.

PMID- 17432258
TI  - Trustees of the Year 2007. Keeping it afloat. Tate works tirelessly after Katrina
      hits home, hospital.

PMID- 17432259
TI  - Trustees of the Year 2007. 'The right thing to do'. Moffitt helps lead fight over
      integrity of disclosures.

PMID- 17432260
TI  - The missing link? Using EHRs to extract data on adverse drug events.

PMID- 17432261
TI  - Introduction to systems biology.
AB  - The developments in the molecular biosciences have made possible a shift to
      combined molecular and system-level approaches to biological research under the
      name of Systems Biology. It integrates many types of molecular knowledge, which
      can best be achieved by the synergistic use of models and experimental data. Many
      different types of modeling approaches are useful depending on the amount and
      quality of the molecular data available and the purpose of the model. Analysis of
      such models and the structure of molecular networks have led to the discovery of
      principles of cell functioning overarching single species. Two main approaches of
      systems biology can be distinguished. Top-down systems biology is a method to
      characterize cells using system-wide data originating from the Omics in
      combination with modeling. Those models are often phenomenological but serve to
      discover new insights into the molecular network under study. Bottom-up systems
      biology does not start with data but with a detailed model of a molecular network
      on the basis of its molecular properties. In this approach, molecular networks
      can be quantitatively studied leading to predictive models that can be applied in
      drug design and optimization of product formation in bioengineering. In this
      chapter we introduce analysis of molecular network by use of models, the two
      approaches to systems biology, and we shall discuss a number of examples of
      recent successes in systems biology.

PMID- 17432262
TI  - Natural and artificially induced genetic variability in crop and model plant
      species for plant systems biology.
AB  - The sequencing of plant genomes which was completed a few years ago for
      Arabidopsis thaliana and Oryza sativa is currently underway for numerous crop
      plants of commercial value such as maize, poplar, tomato grape or tobacco. In
      addition, hundreds of thousands of expressed sequence tags (ESTs) are publicly
      available that may well represent 40-60% of the genes present in plant genomes.
      Despite its importance for life sciences, genome information is only an initial
      step towards understanding gene function (functional genomics) and deciphering
      the complex relationships between individual genes in the framework of gene
      networks. In this chapter we introduce and discuss means of generating and
      identifying genetic diversity, i.e., means to genetically perturb a biological
      system and to subsequently analyse the systems response, e.g., the changes in
      plant morphology and chemical composition. Generating and identifying genetic
      diversity is in its own right a highly powerful resource of information and is
      established as an invaluable tool for systems biology.

PMID- 17432263
TI  - Transcriptional profiling approaches to understanding how plants regulate growth
      and defence: a case study illustrated by analysis of the role of vitamin C.
AB  - In this chapter, basic technical aspects concerning the design of DNA microarray
      experiments are discussed including sample preparation, hybridisation conditions
      and statistical significance of the acquired data are detailed. Given that
      microarrays are perhaps the most used tool in plant systems biology there is much
      experience in the pitfalls in using them. Herein important considerations are
      presented for both the experimental biologists and data analyst in order to
      maximise the utility of these resources. Finally a case study using the analysis
      of vitamin C deficient plants is presented to illustrate the power of this
      approach in enhancing comprehension of important and complex biological
      functions.

PMID- 17432264
TI  - Case studies for transcriptional profiling.
AB  - DNA microarrays are frequently used to study transcriptome regulation in a wide
      variety of organisms. Although they are an invaluable tool for the acquisition of
      large scale dataset in plant systems biology, a number of surprising results and
      unanticipated complications are often encountered that illustrate the limitations
      and potential pitfalls of this technology. In this chapter we will present
      examples of real world studies from two classes of microarray experiments that
      were designed to (i) identify target genes for transcriptional regulators and
      (ii) to characterize complex expression patterns to reveal unexpected
      dependencies within transcriptional networks.

PMID- 17432265
TI  - Regulatory small RNAs in plants.
AB  - The discovery of microRNAs in the last decade altered the paradigm that protein
      coding genes are the only significant components for the regulation of gene
      networks. Within a short period of time small RNA systems within regulatory
      networks of eukaryotic cells have been uncovered that will ultimately change the
      way we infer gene regulation networks from transcriptional profiling data. Small
      RNAs are involved in the regulation of global activities of genic regions via
      chromatin states, as inhibitors of 'selfish' sequences (transposons,
      retroviruses), in establishment or maintenance of tissue/organ identity, and as
      modulators of the activity of transcription factor as well as 'house keeping'
      genes. With this chapter we provide an overview of the central aspects of small
      RNA function in plants and the features that distinguish the different small
      RNAs. We furthermore highlight the use of computational prediction methods for
      identification of plant miRNAs/precursors and their targets and provide examples
      for the experimental validation of small RNA candidates that could represent
      trans-regulators of downstream genes. Lastly, the emerging concepts of small RNAs
      as modulators of gene expression constituting systems networks within different
      cells in a multicellular organism are discussed.

PMID- 17432266
TI  - Differential display and protein quantification.
AB  - High-throughput quantitation of proteins is of essential importance for all
      systems biology approaches and provides complementary information on steady-state
      gene expression and perturbation-induced systems responses. This information is
      necessary because it is, e.g., difficult to predict protein concentrations from
      the level of mRNAs, since regulatory processes at the posttranscriptional level
      adjust protein concentrations to prevailing conditions. Despite its importance,
      quantitative proteomics is still a challenging task because of the high dynamic
      range of protein concentrations in the cell and the variation in the physical
      properties of proteins. In this chapter we review the current status of, and
      options for, protein quantification in high-throughput experiments and discuss
      the suitability and limitations of different existing methods.

PMID- 17432267
TI  - Protein identification using mass spectrometry: a method overview.
AB  - With the introduction of soft ionization techniques such as Matrix Assisted Laser
      Desorption Ionization (MALDI), and Electrospray Ionization (ESI), proteins have
      become accessible to mass spectrometric analyses. Since then, mass spectrometry
      has become the method of choice for sensitive, reliable and inexpensive protein
      and peptide identification. With the increasing number of full genome sequences
      for a variety of organisms and the numerous protein databases constructed
      thereof, all the tools necessary for the high-throughput protein identification
      with mass spectrometry are in place. This chapter highlights the different mass
      spectrometric techniques currently applied in proteome research by giving a brief
      overview of methods for identification of posttranslational modifications and
      discussing their suitability of strategies for automated data analysis.

PMID- 17432268
TI  - Methods, applications and concepts of metabolite profiling: primary metabolism.
AB  - In the 1990s the concept of a comprehensive analysis of the metabolic complement
      in biological systems, termed metabolomics or alternately metabonomics, was
      established as the last of four cornerstones for phenotypic studies in the post
      genomic era. With genomic, transcriptomic, and proteomic technologies in place
      and metabolomic phenotyping under rapid development all necessary tools appear to
      be available today for a fully functional assessment of biological phenomena at
      all major system levels of life. This chapter attempts to describe and discuss
      crucial steps of establishing and maintaining a gas chromatography/electron
      impact ionization/ mass spectrometry (GC-EI-MS)-based metabolite profiling
      platform. GC-EI-MS can be perceived as the first and exemplary profiling
      technology aimed at simultaneous and non-biased analysis of primary metabolites
      from biological samples. The potential and constraints of this profiling
      technology are among the best understood. Most problems are solved as well as
      pitfalls identified. Thus GC-EI-MS serves as an ideal example for students and
      scientists who intend to enter the field of metabolomics. This chapter will be
      biased towards GC-EI-MS analyses but aims at discussing general topics, such as
      experimental design, metabolite identification, quantification and data mining.

PMID- 17432269
TI  - Methods, applications and concepts of metabolite profiling: secondary metabolism.
AB  - Plants manufacture a vast array of secondary metabolites/natural products for
      protection against biotic or abiotic environmental challenges. These compounds
      provide increased fitness due to their antimicrobial, anti-herbivory, and/or
      alleopathic activities. Secondary metabolites also serve fundamental roles as key
      signaling compounds in mutualistic interactions and plant development. Metabolic
      profiling and integrated functional genomics are advancing the understanding of
      these intriguing biosynthetic pathways and the response of these pathways to
      environmental challenges. This chapter provides an overview of the basic methods,
      select applications, and future directions of metabolic profiling of secondary
      metabolism. The emphasis of the application section includes the combination of
      primary and secondary metabolic profiling. The future directions section
      describes the need for increased chromatographic and mass resolution, as well as
      the inevitable need and benefit of spatially and temporally resolved metabolic
      profiling.

PMID- 17432270
TI  - Metabolic flux analysis: recent advances in carbon metabolism in plants.
AB  - Isotopic tracers are used to both trace metabolic pathways and quantify fluxes
      through these pathways. The use of different labeling methods recently led to
      profound changes in our views of plant metabolism. Examples are taken from
      primary metabolism, with sugar interconversions, carbon partitioning between
      glycolysis and the pentose phosphate pathway, or metabolite inputs into the
      tricarboxylic acid (TCA) cycle, as well as from secondary metabolism with the
      relative contribution of the plastidial and cytosolic pathways to the
      biosynthesis of terpenoids. While labeling methods are often distinguished
      according to the instruments used for label detection, emphasis is put here on
      labeling duration. Short time labeling is adequate to study limited areas of the
      metabolic network. Long-term labeling, when designed to obtain metabolic and
      isotopic steady-state, allows to calculate various fluxes in large areas
      ofcentral metabolism. After longer labeling periods, large amounts of label
      accumulate in structural or storage compounds: their detailed study through the
      retrobiosynthetic method gives access to the biosynthetic pathways of otherwise
      undetectable precursors. This chapter presents the power and limits of the
      different methods, and illustrates how they can be associated with each other and
      with other methods of cell biology, to provide the information needed for a
      rational approach of metabolic engineering.

PMID- 17432271
TI  - Network visualization and network analysis.
AB  - Network analysis of living systems is an essential component of contemporary
      systems biology. It is targeted at assemblance of mutual dependences between
      interacting systems elements into an integrated view of whole-system functioning.
      In the following chapter we describe the existing classification of what is
      referred to as biological networks and show how complex interdependencies in
      biological systems can be represented in a simpler form of network graphs.
      Further structural analysis of the assembled biological network allows getting
      knowledge on the functioning of the entire biological system. Such aspects of
      network structure as connectivity of network elements and connectivity degree
      distribution, degree of node centralities, clustering coefficient, network
      diameter and average path length are touched. Networks are analyzed as static
      entities, or the dynamical behavior of underlying biological systems may be
      considered. The description of mathematical and computational approaches for
      determining the dynamics of regulatory networks is provided. Causality as another
      characteristic feature of a dynamically functioning biosystem can be also
      accessed in the reconstruction of biological networks; we give the examples of
      how this integration is accomplished. Further questions about network dynamics
      and evolution can be approached by means of network comparison. Network analysis
      gives rise to new global hypotheses on systems functionality and reductionist
      findings of novel molecular interactions, based on the reliability of network
      reconstructions, which has to be tested in the subsequent experiments. We provide
      a collection of useful links to be used for the analysis of biological networks.

PMID- 17432272
TI  - Current challenges and approaches for the synergistic use of systems biology data
      in the scientific community.
AB  - Today's rapid development and broad application of high-throughput analytical
      technologies are transforming biological research and provide an amount of data
      and analytical opportunities to understand the fundamentals of biological
      processes undreamt of in past years. To fully exploit the potential of the large
      amount of data, scientists must be able to understand and interpret the
      information in an integrative manner. While the sheer data volume and
      heterogeneity of technical platforms within each discipline already poses a
      significant challenge, the heterogeneity of platforms and data formats across
      disciplines makes the integrative management, analysis, and interpretation of
      data a significantly more difficult task. This challenge thus lies at the heart
      of systems biology, which aims at a quantitative understanding of biological
      systems to the extent that systemic features can be predicted. In this chapter,
      we discuss several key issues that need to be addressed in order to put an
      integrated systems biology data analysis and mining within reach.

PMID- 17432273
TI  - Integrated data analysis for genome-wide research.
AB  - Integrated data analysis is introduced as the intermediate level of a systems
      biology approach to analyse different 'omics' datasets, i.e., genome-wide
      measurements of transcripts, protein levels or protein-protein interactions, and
      metabolite levels aiming at generating a coherent understanding of biological
      function. In this chapter we focus on different methods of correlation analyses
      ranging from simple pairwise correlation to kernel canonical correlation which
      were recently applied in molecular biology. Several examples are presented to
      illustrate their application. The input data for this analysis frequently
      originate from different experimental platforms. Therefore, preprocessing steps
      such as data normalisation and missing value estimation are inherent to this
      approach. The corresponding procedures, potential pitfalls and biases, and
      available software solutions are reviewed. The multiplicity of observations
      obtained in omics-profiling experiments necessitates the application of multiple
      testing correction techniques.

PMID- 17432274
TI  - Network analysis of systems elements.
AB  - A central goal of postgenomic research is to assign a function to every predicted
      gene. Because genes often cooperate in order to establish and regulate cellular
      events the examination of a gene has also included the search for at least a few
      interacting genes. This requires a strong hypothesis about possible interaction
      partners, which has often been derived from what was known about the gene or
      protein beforehand. Many times, though, this prior knowledge has either been
      completely lacking, biased towards favored concepts, or only partial due to the
      theoretically vast interaction space. With the advent of high-throughput
      technology and robotics in biological research, it has become possible to study
      gene function on a global scale, monitoring entire genomes and proteomes at once.
      These systematic approaches aim at considering all possible dependencies between
      genes or their products, thereby exploring the interaction space at a systems
      scale. This chapter provides an introduction to network analysis and illustrates
      the corresponding concepts on the basis of gene expression data. First, an
      overview of existing methods for the identification of co-regulated genes is
      given. Second, the issue of topology inference is discussed and as an example a
      specific inference method is presented. And lastly, the application of these
      techniques is demonstrated for the Arabidopsis thaliana isoprenoid pathway.

PMID- 17432275
TI  - Deep vein thromboembolism in malignant diseases.
AB  - Tumourous diseases are associated with haemorrhagic as well as thrombotic
      complications. Trousseau described in 1865 a mutual association between tumourous
      diseases and venous thromboembolism. As many as 15-20% patients with venous
      thromboembolism have an undetected malignity, which equals a prevalence of 2-3%
      in the population. From this ensues the relative risk of a newly diagnosed
      malignity which is higher during the first year after venous thromboembolism.
      Migrating thrombophlebitis is a relatively specific sign in tumours, in
      particular in pancreatic tumours. In the pathogenesis of venous thromboembolisms
      in tumourous diseases, the following factors play a significant part: elevated
      coagulation parameters, reduced fibrinolysis, frequent immobilization, surgical
      operations in the case history, chemotherapy, hormonal therapy and central venous
      catheters. Conventional long term management of VTE involves the use of vitamin K
      antagonists, such as warfarin, to reduce the risk of recurrence. Recent evidence
      based approach in long term management of VTE in patients with tumorous disease
      shows that the use of LMWH offers an effective alternative to VKAs with higher
      efficacy, without a significantly increased risk of bleeding, and without the
      need for regular laboratory monitoring.

PMID- 17432276
TI  - [Extrusion/spheronization: an important method for the production of the pellet
      dosage form].
AB  - Extrusion/spheronization is the method used to manufacture pellets with a high
      content of the active ingredient. It produces particles of very good physical
      properties (strength, friability, porosity, density, uniform diameter), which are
      well processed in further steps, i.e., when they are coated, compressed or filled
      into hard gelatine capsules. The process of extrusion/spheroniztion consists of
      several consequential steps, which are influenced by numerous formulation and
      process factors. Though there are general rules for optimization of the process,
      due to its complexity the same rules need not necessarily be valid for similar
      systems and very often it is necessary to find again the optimal production
      condition for a new formulation and equipment. The paper informs about the
      technology, equipment, and the result achieved in the field.

PMID- 17432277
TI  - The influence of the extrusion die on pellet characteristics.
AB  - Characteristics of pellets (pellet size distribution, their mean diameter,
      density, hardness, friability, repose angle, Hausner ratio, and drug dissolution
      profiles) prepared by axial and radial extrusion/spheronization were examined in
      this experimental study. The formulation consisted of binary mixtures of
      theophylline, a drug slightly soluble in water, and Avicel CL 611 as an
      excipient. Different characteristics were found in the samples prepared using the
      different extrusion dies: the axially situated extrusion die produces the pellets
      of higher hardness and density, and slower dissolution profiles. Differences in
      drug dissolution profiles should be considered, nevertheless they are not
      significant. All pellet samples showed low friability and excellent flow
      properties.

PMID- 17432278
TI  - [Genista tinctoria in vitro].
AB  - The paper deals with the effects of different growth regulators on the growth of
      the culture and production of isoflavonoids in the cultivation of the callus
      culture Genista tinctoria on MS medium under varying light regimens. Of the
      regulators tested, the highest growth of the culture was found when using BAP 10
      mg/l under continuous lighting. With the use of BAP 0.1 mg/l and under normal
      light regimen, the production of genistine and daidzenin was even higher than in
      the intact plant. Of the five isoflavonoids determined, four were demonstrated in
      the callus culture: genistine, genistein, daidzein, and formononetin. In the
      intact plant the authors managed to determine daidzein, genistein, and biochanin
      A.

PMID- 17432279
TI  - [Constituents of Lilium candidum L. and their antioxidative activity].
AB  - The paper deals with the separation and identification of a flavonoid glycoside
      from the petals of Lilium candidum L. and the antioxidative properties of the
      ethanolic extract of the flowers and selected compounds isolated from this
      species. The isolated flavonoid glycoside was identified as isorhamnetin-3-O
      rutinoside by acid hydrolysis, TLC comparison with authentic samples, and UV and
      mass spectra. Isorhamnetin rutinoside was isolated from Lilium candidum L. for
      the first time. The antioxidative activity of the ethanolic extract of the
      flowers and some isolated compounds were determined using DPPH assays.

PMID- 17432280
TI  - [Prescription of hypolipidemic agents in 2001-2004].
AB  - The paper analyzes the development of the prescription and consumption of
      hypolipidemic agents from 2000 to 2004. The principal database consisted of
      dispensed medical prescriptions and the consumption of hypolipidemic agents was
      expressed in DDD, DID, financially, and in the form of proportional
      representation. In the year 2004 hypolipidemic agents represented 11.8% of the
      total costs for medicaments (statins, 8.9%, and 75.6%, respectively, fibrates,
      2.9% and 24.4%, respectively), in DDD statins, 69.0%, fibrates, 31.0%. The most
      frequently prescribed preparation was simvastatin, 57.8% DDD and 60.3% in
      financial units.

PMID- 17432281
TI  - [Consumption of old and new antiepileptic drugs in the Czech Republic in 1999
      2004].
AB  - Trends in antiepileptic drug (AEDs) consumption in the period from 1999 to 2004
      in the Czech Republic were assessed in this study. The data from extramurally
      prescribed, reimbursed AEDs were obtained from the Czech Health Insurance Company
      Skoda Mlada Boleslav. The AEDs utilization was assessed according to ATC/DDD
      methodology on the fourth and fifth level of the ATC classification and expressed
      as the number of defined daily doses per 1000 insured per day (DDD/TID). During
      the study period, the AEDs consumption increased by 130%; 76% of which consisted
      of new AEDs. The most frequently prescribed drugs were carbamazepine and
      valproate. It correlates well with recent guidelines, where carbamazepine and
      valproate are licensed as the first line therapy in the treatment of epilepsy.
      The utilization of barbiturates and hydantoines is decreasing. Gabapentin,
      lamotrigine and topiramate were the most frequently prescribed new AEDs. The
      total cost of AEDs increased three times, 84.5% of this increase accounted for
      new AEDs. The outcomes are in agreement with current recommendations. The AEDs
      consumption follows trends similar to those in other countries with a fast shift
      to new antiepileptic drugs.

PMID- 17432282
TI  - [Analysis of supplying situation in pharmacies. I. Supply with medicaments and
      health appliances from the viewpoint of pharmacies and distributors].
AB  - The paper describes the contemporary methods of ordering, their demands for time,
      and positive and negative aspects. The results of the analysis of the data from
      pharmacies were compared with the data found by analyzing the data provided by
      the distributor. The methodology of the paper includes: a questionnaire survey,
      the method of the autopicture, and an analysis of archival data from pharmacies
      and distributors. The most frequent response to the question concerning the
      number of supplying wholesale distributors is two (38.1% of pharmacies) and three
      (33.3 % of pharmacies); pharmacies receive supplies from them most frequently
      three times a day (28.1% of pharmacies). 61.9 % of pharmacies compile the orders
      intuitively, 38.1% of them use the possibilities of the automatic proposal of the
      order using a PC system. 66.6% of pharmacies utilize modem ordering whose
      advantages are rapidity (493%), time availability (41.2%), a list of confirmed
      preparations (28.5 %), and financial advantageousness (23.8 %). The average time
      of ordering amounts to 21 min a day for telephone orders and 4 min a day for
      modem orders, the average proportion in the use of the individual methods of
      ordering is 59.1% to 40.9% of items to the benefit of modem orders. A concrete
      pharmacy was selected to demonstrate the effect of changes resulting from the
      transition from exclusively telephonic ordering to prevalently modem ordering;
      saved time period amounted to 62.5 % (from 14.4 s to 5.4 s per 1 ordered item).
      The analysis of distributors' data reveals an increase in the share of the items
      and packages ordered via modem (from 22.2%, and 20.6%, respectively, in the year
      2000, to 54.5% and 49.8%, respectively, in the year 2004).

PMID- 17432283
TI  - [Short-term prognosis of transient ischemic attacks. Mexican multicenter stroke
      registry].
AB  - BACKGROUND: There are no data on Mexican population referring to frequency and
      prognosis of transient ischemic attacks (TIA). The purpose of the present study
      was to: (1) estimate the prevalence, vascular risk factors and short-term outcome
      in patients with TIA included in the first Mexican registry of cerebrovascular
      disease, and (2) analyze the acute care provided in these patients. PATIENTS AND
      METHODS: This national registry of cerebrovascular diseases is a multicenter,
      observational, and hospital-based registry that was conducted from November 2002
      to October 2004. The registry was developed to improve our knowledge in Mexico
      regarding risk factors profile, outcome, current diagnostic and treatment
      strategies, and short-term follow-up in patients with acute cerebral ischemia.
      Standardized data assessment was used by all centers which included information
      on demographics, pre-hospital events (including stroke onset and arrival to
      hospital), emergency department triage and workup. Short-term outcome was
      evaluated at day 30. Of this registry, TIA cases were selected and associated
      risk factors, clinical characteristics, diagnosis and treatment were analyzed.
      RESULTS: During the study time period, 2,000 patients were enrolled; 97 (5%) with
      diagnosis of TIA; 51 women and 46 men, mean age 69.3 +/- 11.4 years. Among these
      97 patients; 51 (52.6%) were admitted to the hospital for evaluation. The main
      risk factors were; age > or = 65 years in 74%, hypertension in 64%, diabetes in
      45%, and dislipidemia in 36% and obesity in 31%. The affected arterial territory
      was carotid TIA in 74% and vertebrobasilar in 26%. TIA was attributed to
      atherosclerosis in 63% of the patients, cardioembolism in 17%, and small vessels
      disease in 5%. At 30 days follow-up; three patients died during the initial
      evaluation (two secondary to cardiac arrhythmia, and one secondary to pneumonia).
      Among 14 of the 94 survivors (14.9%) we documented an early stroke recurrence,
      including cerebral infarction in nine patients (9.6%) and new TIA in five cases
      (5.3%). Considering death and cerebral infarction, the frequency of unfavorable
      major events was 12.4%. There were only three cases treated with carotid
      endarterectomy. CONCLUSIONS: The short-term risk of ischemic stroke, death or
      recurrent in TIA patients is high. These findings emphasize that all patients
      with TIA should undergo rapid investigation and management to prevent a major
      stroke and other vascular events.

PMID- 17432284
TI  - [Effectiveness of a cognitive-behavioural program to reduce anxiety in medically
      ill patients].
AB  - The aim of this work is to evaluate four programs to reduce anxiety in medically
      ill patients: psicoeducative, cognitive, behavioural or control. One hundred and
      seventy seven patients from the Instituto Nacional de Ciencias Medicas y
      Nutricion Salvador Zubiran were assigned randomly to one of this programs and
      were evaluated before and after them with the Anxiety Hamilton Scale and the
      State-Trait Anxiety Inventory (STAI). Program effectiveness was evaluated with
      descriptive and a Pre-post difference mean analysis. Results show that the
      program that obtained the best results in reducing anxiety levels was the
      Psicoeducative Program, reducing significantly the anxiety levels evaluated with
      both measures. This indicates that in patients that assist to a general hospital,
      the combination of different psychological techniques such as providing
      information to the patient, relaxation training and other cognitive strategies
      are effective in reducing tension, worries, nervousness and levels of anxiety
      related with their illness.

PMID- 17432285
TI  - [Fluoroquinolone prophylaxis utility during chemotherapy-induced severe
      neutropenia in patients with acute leukemia, with fluoroquinolone resistance high
      prevalence, in a reference hospital in Mexico City].
AB  - BACKGROUND: The use of fluoroquinolone prophylaxis in patients with cancer and
      neutropenia has failed to show a significant impact on mortality, despite its
      usefulness in reducing the incidence of gramnegative bacteremia. However, an
      increase in grampositive bacteremia and the emergence of resistant colonizing
      bacteria have consistently been noticed. OBJECTIVE: To determine the impact of
      prophylaxis with fluoroquinolones on the incidence of bacteremia and mortality in
      a hospital with high fluorquinolone resistance in Mexico City. PATIENTS: We
      conducted a retrospective and comparative study of patients with acute mieloid
      (AML) and hybrid (HL) leukemia who received or not prophylaxis with
      fluoroquinolones and who were attended from January 2000 to December 2003. We
      reviewed all pertinent clinical and laboratory data of the hematologic
      malignancies and the febrile episodes. RESULTS: A total of 108 febrile episodes
      of severe neutropenia occurred in 69 patients, with an incidence of 6.5
      events/1000 day-patient with neutropenia. The median age was 35 +/- 18.3 years
      and 58% were men; 51 patients had AML (71.8%) and 20 (28.1%) HL. Prophylaxis had
      been given since the beginning of granulocytopenia in 46 (42.6%) febrile episodes
      (group 1), where as in 62 no prophylaxis was given (group 2). Of the 46 episodes
      with prophylaxis, 27 received ciprofloxacin 500 mg qd p.o. and 19, ciprofloxacin
      500 mg qd po plus fluconazol 100 mg qd po. The median duration of prophylaxis was
      8.5 days (range 1-90 days). Twenty-nine bacteremias (26.8%) were documented, with
      an incidence of 16.4 bacteremias/1000 day-patient with neutropenia, 12 (26%) in
      group 1 and 17 (27.5%) in group 2. Bacteremia was most frequently caused by gram
      negative organisms (18/29), being Escherichia coli (14) the most commonly
      isolated pathogen, with 7 episodes in each group. Eight (29.6%) of the 21
      isolates in which fluoroquinolone susceptibility was tested were ciprofloxacin
      resistant, 3 in group 1 and 5 in group 2 (p = 0.58). Median survival of patients
      was 38 days in group 1 and 40 days in group 2. (p = 0.2); mortality was similar
      in both groups, 34% and 27%, respectively. CONCLUSIONS: In a hospital with a high
      prevalence of fluoroquinolone-resistance, prophylaxis in patients with acute
      leukemia and severe neutropenia did not prevent febrile episodes and did not have
      any impact on mortality. However, there was no increase in infections caused by
      resistant bacteria.

PMID- 17432286
TI  - [Morbi-mortality related to ileostomy and colostomy closure].
AB  - INTRODUCTION: The main goal of gastrointestinal stomas is to divert the faecal
      stream from technically difficult anastomoses or intestinal obstruction. Current
      tendency is to avoid definitive stomas, temporary loop stomas are commonly used
      to protect high risk anastomosis or sections of the distal bowel. The aim of this
      study was to determine and compare the morbi-mortality after loop stomas closure.
      METHODS: Retrolective, observational and comparative study was conducted. The
      files of patients submitted to loop ileostomy or colostomy closure from 1981 to
      2001 were reviewed. Statistical analysis was performed by the Fisher's exact test
      and the Mann-Whitney U test. RESULTS: From a total of 107 procedures included,
      73% were ileostomy closures and 27% colostomy closures. The mean age was 46 years
      (14-88). Protection of anastomoses was the most common indication in both stoma
      groups. The colostomy group had a larger interval days between stoma creation and
      closure than the ileostomy group (172.3 days vs. 125.6 days p = 0.008). Stoma
      closure was performed by hand sewn sutures in 81.3% patients and by stapled
      technique in 19.7% patients. The mean operative time for stoma closure was higher
      for colostomy group than for ileostomy (108.1 min vs. 88.3 min, p = 0.04).
      Colostomy group patients required a midline abdominal incisions more often than
      ileostomy group (21.4 vs. 2.5% p = 0.04). Morbidity rates were 7.6% for the
      ileostomy group and 10.3% for the colostomy group. Colostomy closure required a
      longer length of stay. There was no mortality. CONCLUSION: The results of this
      study showed that stoma closure was a well tolerated procedure with low morbidity
      and no mortality rates. The result suggest that ileostomy closure is a simpler
      procedure.

PMID- 17432287
TI  - [International family medicine certification exam in Venezuela: the physician's
      experience].
AB  - OBJECTIVE: To present opinions of physicians participating in a pilot
      certification exam in the specialty of Family Medicine implemented in Venezuela,
      in December 2004, by the Mexican Board of Certification of Family Medicine A.C.
      DESIGN: Descriptive, transversal. METHODS: Participant physicians (n:37)
      completed semi-structured questionnaries: one or two weeks before the exam, and
      immediately after it. RESULTS: 60% of participants were 41-50 years old and 80%
      women. All of them were practicing physicians; 49% had 5-10 year experience in
      family medicine. Main motivation to participate in the exam: the need for
      continuing learning (83%). Results showed their participation motivated
      continuing education (46%). Books were the most frequently utilized resource when
      preparing for the exam (54%). 94% were willing to take the exam again in the
      future, and all would recommend it to their colleagues. 49% said that examination
      should be taken every 3-4 years and should be voluntary (54%). 86% considered the
      content of the exam pertinent to their practice while 54% mentioned it was well
      adapted to their country's reality. Time for the exam was enough according to
      71%, and number of questions was considered excessive by 89%. After the exam, 43%
      estimated to have personal prognosis for excellent or good outcomes. CONCLUSIONS.
      The international examination was satisfactory, stimulated desires of update, and
      the participants would repeat and recommend it in the future. The Mexican
      experience offers an example to put into practice, and the international
      collaboration would be a valid option to extend the certification processes in
      Latin America.

PMID- 17432288
TI  - [Seropositivity of HIV, HBV, HCV and Treponema pallidum in blood donors in
      southeast Mexico].
AB  - OBJECTIVE: To determine the prevalence of serological markers for the human
      immunodeficiency virus (HIV), hepatitis B (HVB) and C (HCV) viruses, and
      Treponema pallidum in blood donors. MATERIAL AND METHODS: The results of the
      screening tests from blood donors studied at the Central Blood Bank of the
      Ignacio Garcia Tellez National Medical Center, in Merida, Yucatan, Mexico between
      January 2002 and December 2004, have been retrospectively evaluated. RESULTS: Of
      39,933 blood donors, 424 (1.06%) were positive to one or more serological
      markers. The seropositivity rates for anti-HIV, HBsAg, anti-HCV and anti
      Treponema pallidum were found as 0.13%, 0.20%, 0.44% and 0.29%, respectively.
      Western Blot positive was found in 41 (77.36%) of the 53 blood donors positive
      for anti-HIV. CONCLUSIONS: In this study, the prevalence of serological markers
      was similar or lower than that reported in previous studies in Mexico.

PMID- 17432289
TI  - Detection of Mycobacterium tuberculosis from respiratory samples with the liquid
      culture system MB/BacT and verified by PCR.
AB  - OBJECTIVE: To assess the performance in the clinical setting of the MB/BacT
      system for isolation of Mycobacterium tuberculosis and to verify by PCR. MATERIAL
      AND METHODS: The study included 272 sputum samples from 208 patients with the
      presumptive diagnosis of pulmonary tuberculosis. ZN was made, culture in
      Lowenstein-Jensen medium, MB/BacT and PCR. RESULTS: Thirty-nine samples were
      positive by culture in Lowenstein-Jensen, and 42 using the MB/BacT system.
      Positive cultures in the MB/BacT system were verified by acid-fast bacilli
      staining and PCR. Mycobacterial identification in the MB/BacT took 8 to 46 days
      (mean 16 days), while the Lowenstein-Jensen culture ranged between 21 and 63 days
      (mean 35 days). These results show that the MB/BacT semiautomated system is
      reliable and faster than the manual culture method and can be used as an
      alternative for the primary identification of Mycobacterium tuberculosis. The PCR
      assay allows the fast and exact identification of Mycobacterium tuberculosis
      directly from positive liquid medium.

PMID- 17432290
TI  - [Molecular study of methicillin-resistant Staphylococcus haemolyticus in a
      Mexican hospital].
AB  - OBJECTIVE: To perform the molecular characterization of methicillin-resistant
      Staphylococcus haemolyticus (MRSH) clinical isolates from patients in a Mexican
      hospital. METHODS: Sixty three Staphylococcus ssp. isolates collected from
      September 2000 to October 2002 were analyzed. Antimicrobial susceptibility was
      determined by disk diffusion method and the presence of the mecA gene was
      detected by PCR technique. Isolates characterization was carried out by pulsed
      field gel electrophoresis (PFGE). RESULTS: The frequency of S. haemolyticus was
      25.5% (18 of 63 clinical isolates), all S. haemolyticus isolates were methicillin
      resistant and they were positive for the mecA gene. A major pattern (A) with 8
      subtypes was identified. This clone was distributed during the 20 months period.
      Most of them were isolated from the surgery (55%) and pediatric services (27.5%).
      CONCLUSION: The methicillin-resistant S. haemolyticus permanence as pathogen in
      this hospital, suggest the implementation of control programs in order to
      decrease the prevalence of this multiresistant pathogen.

PMID- 17432292
TI  - [Sepsis caused by methicillin-resistant Staphylococcus aureus: the shadow of a
      persistent threat].
AB  - Clinical case. This 27 year-old male was referred admitted with severe acute
      pancreatitis (SAP) after heavy consumption of alcohol and sepsis (bacteremia and
      multilobar pneumonia) due to methicillin-resistant Staphylococcus aureus (MRSA);
      he required mechanical ventilation and haemodyalisis, and developed fungemia by
      fluconazol-resistant Candida albicans. He was treated with caspofungin for 20
      days and vancomycin for six weeks, and he was discharged after 51 days of
      hospitalization. This case shows the painful evolution of a patient admitted to
      the intensive care unit (ICU) with MRSA sepsis. According to the National
      Nosocomial Infections Study (USA), S. aureus is the cause of up to 35% of
      hospital-acquired pneumonia and bacteremia. Using molecular tools (e.g. pulse gel
      electrophoresis), different families of MRSA have been well described. Use of
      i.v. catheters, long-term hospitalization, surgery and previous use of
      antimicrobials are considered major risk factors for MRSA. In Mexico, Alpuche
      Aranda, et al (1986) reported a prevalence of 5% in a pediatric hospital.
      However, a recent report from the National Resistance Network showed a MRSA
      prevalence of 36% in 2004. In this institution, we observed a rate of MRSA of
      100% in the ICU during 2005. This case shows an episode of SAP after heavy
      alcohol consumption, complicated with severe infections such as candidemia and
      MRSA sepsis; fortunately he had a favorable outcome after a multidisciplinary and
      aggressive approach. This case fulfilled all the risk factors for an MRSA
      infection, in a setting with a very high rate of methicillin-resistance, which
      compels the medical community to implement adequate and efficacious
      epidemiological control measures.

PMID- 17432291
TI  - [Toward cervical cancer prevention: strategies employed in the development of HPV
      vaccines].
AB  - An HPV persistent infection is doubtless the main factor involved in cervical
      cancer development. It is clear that the majority of HPV infections are self
      limited and not all high-risk HPV infections are destined to progress to a higher
      grade lesion. Due to viral mechanisms that evade the immune system, in some cases
      the immune response against HPV is not as effective, allowing the establishment
      of persistent infections. The promise of a vaccine that can avoid HPV infections
      and therefore decrease cervical cancer incidence, has been motive of great
      interest and enthusiasm on the search of different strategies for obtaining an
      effective vaccine. At present, several prophylactic vaccines have been developed
      based in virus like particles (VLPs) produced with L1 viral proteins. Results of
      these vaccines applied to women between 16 and 23 years old show high
      tolerability and immunogenicity with higher antibody titers than those seen in an
      HPV natural infection. Even these vaccines can not wholly prevent infections
      caused by HPV types included in the vaccine design; its efficacy has been
      demonstrated for their ability to eliminate HPV persistent infections and to
      prevent the development of cervical intraepithelial neoplasia. These vaccines are
      currently in phase III of clinical trials, whose results will determine its
      impact in the general population. Therapeutic vaccines are focused in the
      elimination of established cervical lesions; nevertheless their efficacy has not
      been proved for clinical use.

PMID- 17432293
TI  - [Subclinical thyroid dysfunction. Diagnostic and therapeutic considerations].
AB  - Mild thyroid dysfunction is a biochemical diagnosis classified either as
      subclinical hypo or hyperthyroidism. It can occur in young patients with a
      frequency that increases with age, presenting higher morbidity and mortality
      then. To suspect the diagnosis, it is important to keep in mind some of the
      nonspecific signs and symptoms of the disease, and the possible laboratory
      abnormalities. Furthermore, it is advisable to establish an appropriate range of
      values for thyrotropin (TSH), determine the presence of high risk factors in
      individuals under evaluation, and the possible consequences on their well-being.
      Taking into consideration that a non-excessive, adequate hormonal substitution
      prevents, improves or resolves the harmful effect on different systems of the
      organism; as well as an early and opportune detection and treatment of mild or
      subclinical thyroid dysfunction could be beneficial for the general population.

PMID- 17432294
TI  - [Comments by Cicero MD to Santillan MD].

PMID- 17432295
TI  - [CME-ECG 16. Narrow and wide complex tachycardia].

PMID- 17432296
TI  - [Non infectious postoperative fever].
AB  - We present the case of a 74-years old man with subtotal gastrectomy for
      adenocarcinoma, whose postoperative course is complicated by a prolonged fever.
      Despite extensive diagnostics, the origin of the postoperative fever remains
      unexplained for 47 days, when the patient is transferred to the ICU because of
      lethargy, hemodynamic instability, lung edema and abdominal symptoms. The
      diagnosis of Addison crisis is established and under substitution with
      hydrocortisone all the symptoms rapidly resolve. Postoperative fever is
      relatively frequent and infectious causes account for about half of the cases
      only. An infectious origin has imperatively to be excluded when the fever arises
      later than 48 hrs after surgery. In case of prolonged fever we suggest to extend
      the differential diagnosis to other than infectious causes by means of special
      lists (e.g fever of unknown origin).

PMID- 17432297
TI  - [Posttraumatic right sided diaphragmal hernia].
AB  - This case report demonstrates a post-traumatic right sided diaphragmal hernia
      presenting 17 years after trauma with acute abdominal pain. An incarcerated
      duodenal bowel loop was radiologically suspected and confirmed by subsequent
      surgery.

PMID- 17432298
TI  - [Hypoglycemia in infancy -- not always of no importance!].
AB  - A six month old boy is admitted to the children's hospital for sudden loss of
      consciousness. Hypoglycemia is diagnosed and corrected. Further investigations
      reveal the diagnosis of hyperinsulinism as underlying cause for hypoglycaemic
      episodes. Differential diagnosis and therapy of hypoglycemia in infancy are
      discussed.

PMID- 17432299
TI  - [Inflammation-induced upper abdominal pain. A 39-year-old economist].

PMID- 17432300
TI  - [Delayed upper abdominal pain and tarry stool after transjugular liver biopsy. A
      24-old man with hemophilia].
AB  - A 24-year old patient with severe haemophilia A and chronic hepatitis C developed
      two weeks after transjugular liver biopsy (TJLB) haemobilia with colicky upper
      abdominal pain, coffee ground emesis, melaena and anaemia. Abdominal ultrasound
      and endoscopic retrograde cholangiogram confirmed the diagnosis. After adequate
      factor VIII substitution and revision with a balloon catheter the patient became
      asymptomatic. Haemobilia is a uncommon complication after liver biopsy. This
      complication should be kept in mind even if the occurrence is delayed after
      intervention. TJLB is an established and safe method to obtain liver specimen in
      patients with coagulation disorders.

PMID- 17432301
TI  - Births: preliminary data for 2005.
AB  - OBJECTIVES: This report presents preliminary data for 2005 on births in the
      United States. U.S. data on births are shown by age, live-birth order, race, and
      Hispanic origin of mother. Data on marital status, cesarean delivery, preterm
      births, and low birthweight (LBW) are also presented. METHODS: Data in this
      report are based on 99.2 percent of births for 2005. The records are weighted to
      independent control counts of all births received in state vital statistics
      offices in 2005. Comparisons are made with 2004 data. RESULTS: The crude birth
      rate in 2005 was 14.0 births per 1,000 total population, unchanged from 2004. The
      general fertility rate, however, rose to 66.7 births per 1,000 women aged 15-44
      years in 2005, the highest level since 1993. The birth rate for teenagers
      declined by 2 percent in 2005, falling to 40.4 births per 1,000 women aged 15-19
      years, the lowest ever recorded in the 65 years for which a consistent series of
      rates are available. The rate declined for teenagers 15-17 years to 21.4 births
      per 1,000, but was essentially stable for older teenagers 18-19 years. The birth
      rate for women aged 20-24 years rose in 2005, whereas the rate for women aged 25
      29 years was essentially unchanged. The birth rates for women aged 30 years and
      over rose to levels not seen in almost 40 years. Childbearing by unmarried women
      increased to record levels for the Nation in 2005. The birth rate rose 3 percent
      to 47.6 births per 1,000 unmarried women aged 15-44 years; the proportion of all
      births to unmarried women increased to 36.8 percent. The cesarean delivery rate
      rose by 4 percent in 2005 to 30.2 percent of all births, another record high for
      the Nation. The preterm birth rate continued to rise (to 12.7 percent in 2005) as
      did the rate for LBW births (8.2 percent).

PMID- 17432302
TI  - More core measure data for 2008: don't neglect your internally defined
      priorities.

PMID- 17432303
TI  - Hospital hit by tornado shares lessons learned.

PMID- 17432304
TI  - Patients may define medical errors differently than you.

PMID- 17432305
TI  - Discharge planning Advisor. Administrators fall short of full recognition of CM
      duties.

PMID- 17432306
TI  - Discharge planning Advisor. It takes all CM functions to provide necessary care.

PMID- 17432307
TI  - Best practices found in survey at KY hospital.

PMID- 17432308
TI  - Fault trees uncover complex causes.

PMID- 17432309
TI  - Patient Safety Alert. Integrated community effort wins Codman for FL hospital.

PMID- 17432310
TI  - Methadone as an analgesic: a review of the risks and benefits.
AB  - While methadone has been available for over 50 years, its use in opiate
      dependence has overshadowed its use as an analgesic. Within the last 10-15 years,
      though, methadone has been increasingly used to manage neuoropathic pain and
      cancer pain, but its use is causing an alarming number of deaths in the U.S. Last
      June, The Charleston Gazette ran a series titled "The Killer Cure" by Scott Finn
      and Tara Tuckwiller that found that the number of Americans whose deaths were
      caused by methadone rose from 790 in 1999 to 2,992 in 2003. The series also
      reported other statistics from the National Center for Health Statistics that
      revealed that West Virginia ranked first per capita in methadone overdose deaths,
      and that methadone was more likely involved in overdose deaths than any other
      prescription drug. Methadone has several unique properties that can be beneficial
      in the treatment of neuropathic pain and cancer pain unresponsive to other
      opioids, but some of these properties make it very dangerous and difficult to
      prescribe properly. As a result of these factors, methadone should not be the
      first-choice drug for pain and it should not be used in opioid-naive patients.
      The goal of this article is to provide a review of the properties and protocols
      for safe prescribing of methadone to help physicians recognize situations where
      this drug offers the greatest advantage as an analgesic.

PMID- 17432311
TI  - Re-measurement data for the heart failure "GAP in the Mountains" project shows
      major improvements.

PMID- 17432312
TI  - The quantitative immunoturbidimetric D-dimer method to rule out venous
      thromboembolism (VTE).
AB  - D-dimer measurement is a technique that may improve the diagnostic strategy for
      venous thrombo-embolism (VTE). To evaluate D-dimer accuracy in the diagnosis of
      VTE, we identified 116 patients at Charleston Area Medical Center in Charleston,
      W.Va., for whom D-dimer assay had been performed to screen for VTE. Forty-one had
      VTE diagnosis confirmed (VTE-Positive); and 75 were ruled out (VTE-Negative); all
      by radiologic studies. D-dimer values for 41 healthy individuals were also
      prospectively collected. D-dimer value ranges of VTE-Positive, VTE-Negative and
      Healthy Sample groups were 0.5-55, 0.5-15.9, and 0.4-3.24 mg/L. Cutoff values of
      2.5, 2.1, 1.6, and 1 mg/L had sensitivities of 74%, 81%, 86% and 95%, with
      specificities of 60%, 48%, 32% and 12%, respectively. Negative predictive values
      were 80%, 81%, 79% and 82%, while positive predictive values were 52%, 48%, 43%
      and 39%, respectively. Our results show that quantitative D-dimer assays lack the
      accuracy to serve as a method for ruling out VTE.

PMID- 17432313
TI  - Osteoporosis by forearm bone densitometry in postmenopausal women in West
      Virginia.
AB  - Forearm bone densitometry examination predicts the relative risk of osteoporotic
      fracture, but not as reliably as central densitometry of the hip and spine. The
      ease of performance, inexpensiveness, and mobility of this technique makes it
      especially appealing in rural states like West Virginia. After evaluating 1,321
      Caucasian women in West Virginia by peripheral bone densitometry at the proximal
      1/3 radius region, we found a 26.6% prevalence of osteoporosis. This is higher
      when compared to estimates using central densitometry and could potentially lead
      to overprescribing of expensive medications. Although central densitometry is the
      preferred method for the diagnosis of osteoporosis, women ages 65 or older with
      osteoporosis identified by peripheral densitometry should likewise be treated.
      Clinical risk factors should be present before initiating treatment in younger
      postmenopausal women ages 50-64. In those women without risk factors,
      confirmation by central densitometry should be performed if possible.

PMID- 17432314
TI  - [Conditioned reflex: detector and command neuron].
AB  - Conditioned reflex is characterized by plasticity resulting in a bilateral
      selective input-output linking. In simple nervous systems, input stimuli are
      represented by selective detectors connected with command neurons through plastic
      synapses strengthened during associative learning and weakened during extinction.
      The process of associative learning is due to temporal coincidence of excitation
      in both detector and command neurons. Short-term memory within a plastic synapses
      is mediated by phosphorilation of postsynaptic receptor molecules not requiring
      protein synthesis. Long-term synaptic memory parallels expression of immediate
      early genes that mediates structural gene expression and protein synthesis. A
      simple detector-command neuron association becomes more complex in the course of
      evolution. Input mechanism is supplemented with predetector interneurons
      preceding detectors. Detector selectively tuned to specific input stimulus is
      converging on a command neuron constitute selectivity mechanism for conditioned
      reflexes to complex stimuli. The complication also concerns the output
      mechanisms. Command neurons become more specialized, and an additional link of
      premotor interneurons is incorporated between command neurons and motor neurons.
      Via synapses, the command neurons can produce excitation in a particular set of
      premotor neurons controlling a specific set of motor neurons responsible for
      behavioral act configuration. Specialization of command neurons in combination
      with premotor neuron structures increases the variability of outputs. Conditioned
      reflexes with more complex inputs and more flexible outputs determine the
      diversity of acquired behaviors.

PMID- 17432315
TI  - [Human fast negative EEG potentials before express saccades].
AB  - Fast negative EEG potentials preceding fast regular saccades and express saccades
      were studied by the method of backward averaging under conditions of monocular
      stimulation of the right and left eye. "Step" and "gap" experimental paradigms
      were used for visual stimulation. Analysis of parameters of potentials and their
      spatiotemporal dynamics suggests that, under conditions of the increased
      attention and optimal readiness of the neural structures, express saccades appear
      when the previously chosen program of the future eye movement coincides with the
      actual target coordinates. We assumed that the saccade latency decreases at the
      expense of the involvement of the main oculomotor areas of motor and saccadic
      planning in its initiation; an express saccade can be initiated also by means of
      direct transmission of the signal from the cortex to the brainstem saccadic
      generator passing by the superior colliculus. Moreover, anticipating release from
      the central fixation and attention distraction are necessary for the successful
      initiation of an express saccade.

PMID- 17432316
TI  - [Changes in the spatial organization of the cortical electrical activity during
      formation and actualization of a cognitive set to facial expression].
AB  - Coherence function of the EEG in the bands of 8-13 (alpha rhythm) and 14-25 Hz
      (beta rhythm) was analyzed in 35 healthy adult subjects during formation and
      testing of a visual cognitive set to pictures of faces with different emotional
      expressions. The intra- and interhemispheric coherences of the potentials in the
      frontal area and coherence between the right frontal and temporal derivation were
      shown to increase at the stage of set actualization. The results of the analysis
      confirm the suggestion that the frontal cortical areas are predominantly involved
      in formation and actualization of the set to facial emotional expression. The
      conclusion is based on the idea that the spatial synchronization of the brain
      electrical potentials is an index of the functional relations between the
      corresponding cortical areas and their cooperative involvement in a certain kind
      of activity (their simultaneous activation).

PMID- 17432317
TI  - [Effect of "animal hypnosis" on the rhythmic defensive dominanta].
AB  - A defensive dominanta (stationary excitation focus) in the sensorimotor cortex of
      rabbits was formed by rhythmical electrodermal paw stimulation with the frequency
      of 0.5 Hz. After cessation of the stimulation, the state of hidden excitation was
      tested with acoustic stimuli, in response to which nonrhythmic activity of leg
      muscles increased or the leg rhythmically startled with the frequency close to
      that of the electrodermal stimulation. After conducting a routine hypnotizing
      procedure, the incidence of the rhythmic responses to testing stimulation
      increased, while the incidence of nonrhythmic responses decreased.

PMID- 17432318
TI  - [Medial septal region as a target for modulation of seizure discharges in the
      hippocampus in a model of acute temporal lobe epilepsy].
AB  - Investigation of changes in the hippocampal EEG produced by GABAergic and
      cholinergic substances delivered into the medial septum region was performed in
      awake rabbits. Changes in the threshold of seizure discharges in the hippocampus
      evoked by perforant path stimulation (model of acute epilepsy) were also
      examined. Injections of GABAA receptor antagonist picrotoxin or agonist of
      cholinergic receptors carbacholine in low doses induced an increase in the power
      of delta- and theta modulation and appearance of 7-12-Hz oscillations. The
      threshold of hippocampal seizure afterdischarges decreased. In higher doses,
      these substances evoked 7-15-Hz oscillations followed by seizures. GABAA receptor
      agonist muscimol and muscarinic receptor antagonist scopolamine decreased the
      power of the theta rhythm and increased the seizure threshold. Picrotoxin or
      carbacholine injected after muscimol or scopolamine, respectively, did not evoke
      seizures. Thus, we have shown the possibility to control hippocampal activity by
      local changes in the GABAergic and cholinergic systems of the medial septum
      region.

PMID- 17432319
TI  - [Differentiation of the bimodal stimuli in a frog's retina].
AB  - In work electric activity of frog's retina was investigated by silent
      substitution technique. Electroretinogram was recorded as a response to abrupt
      exchange of the referent stimulus-line with fixed values of luminance and
      orientation to test lines with varied luminance and orientations. As a result of
      the analysis it has been allocated two types of responses of a retina. The
      response to onset-offset of a stimulus-line was similar to the response at
      homogeneous illumination of a retina (ERG), and was characterized by both the
      high amplitude of b-wave (hundreds mkV) and significant asymmetry of b- and d
      waves. Whereas the same waves in response to substitution of the same stimuli
      were more symmetric and had on ten times smaller amplitudes. Such activity of
      frog's retina was referred as pattern electroretinogram (PERG) recorded in a high
      vertebrate's retina as response to stimuli whose contrast was temporally
      modulated. The analysis of interaction of luminance and line orientation channels
      in retina was carried out on the base of construction V-shaped functions of
      stimuli differentiation. It has shown, that activities of both channels are
      linearly summarized in PERG. It means independent and parallel functioning of
      these mechanisms. However, it takes the short subdivision of luminance, namely,
      when luminance of test line not far from luminance of referent line. At the same
      time, from the moment of the double prevalence of test line in relation to
      referent line, growth of PERG amplitude has nonlinearly form. Such two-stage
      changing of PERG amplitude speaks presence in a retina of a frog of two
      mechanisms of coding of luminance. One mechanism coding light intensity by power
      of the discharge, it forms the information on an absolute level of light in the
      environment. Its activity is caused basically, by receptors and cells of external
      plexiform layer and is submitted by b-wave of electroretinogram. Other mechanism
      submitted in PERG, is based on the vector code of stimulus, it forms the
      information on spatial and time differentiation of a light in the visual field
      and is connected, basically, with cells of internal plexiform layer of frog's
      retina.

PMID- 17432320
TI  - [Mechanisms of achromatic vision in snail Helix lucorum L.: intracellular study
      of light-sensitive cells in retina].
AB  - Intracellular study of the eye of land snail Helix lucorum L. demonstrated two
      types of visual cells responding to flashes of white light by slow sustained
      depolarization (D - type) and by slow sustained hyperpolarization (H - type).
      Peaks of spectral sensitivity of both types at 465-500 nm coincide with the peak
      of spectral sensitivity of photopigment 'rhodopsin'. The revealed D- and H -
      cells in the snail retina are considered as analogous of B- and D - cells,
      respectively, in the vertebrate visual system.

PMID- 17432321
TI  - [Functional significance of monoamine- and aminoacidergic mechanisms of dorsal
      pallidum in anxiety of different aversive genesis].
AB  - Microinjections of serotonin and glutamine acid into the globus pallidus reveal
      antiaversive properties of these subsrances in the test with avoiding
      "threatening situation" but not "illuminated site" test under conditions of rats'
      free choice between light and dark sites. Dopamine and GABA injected locally into
      this formation of basal ganglia do not affect the mechanisms of voluntary
      movement, but counteract the conditions of anxiety in both models of behavior.
      The results testify to unequal involvement of neurotransmitter systems of the
      dorsal pallidum into operative regulation of behavior with changes of aversive
      stimulus modality.

PMID- 17432322
TI  - [Dopamine-dependent character of depressive-like behavior in WAG/Rij rats with
      genetic absence epilepsy].
AB  - Placebo-treated WAG/Rij rats (as compared to normal Wistar rats without seizure
      pathology) exhibited depressive-like behavior similar to that of intact rats of
      the same strain: decreased exploratory activity in the open field test, increased
      immobility in the forced swimming test, decreased sucrose consumption and
      preference (anhedonia). Chronic injection of tricyclic antidepressant imipramine
      (15 mg/kg. i.p., for 15 days) exerted a therapeutic (antidepressant) effect on
      depressive-like behavior in WAG/Rij rats. After cessation of antidepressant
      therapy, the behavior of WAG/Rij rats didn't significantly differ from that of
      Wistar rats. Acute (single) injection of selective D2/D3 dopamine receptor
      antagonist raclopride (100 microg/kg, i.p., 15 min prior to behavioral testing)
      aggravated the symptoms of depressive-like behavior and suppressed antidepressant
      effect of chronic injection of imipramine in WAG/Rij rats, whereas it didn't
      exert a substantial effect on behavior of Wistar rats. Injection of D2/D3
      dopamine receptor agonist Parlodel (bromocriptine) counteracted the depressive
      like behavior in WAG/Rij rats and didn't exert substantial influence on behavior
      of Wistar rats with the exception of a decrease in immobility time in the forced
      swimming test. Injections of imipramine and raclopride didn't exert significant
      influences on the level of general locomotor activity and anxiety both in WAG/Rij
      and Wistar rats. The results demonstrate the dopamine-dependent character of
      depressive-like behavior in WAG/Rij rats, and indicate possible involvement of
      dopamine D2-like receptors in mediation of the antidepressant effect of
      imipramine on genetically determined depressive-like behavior in WAG/Rij rats.

PMID- 17432324
TI  - Hepatitis B and the healthcare worker.

PMID- 17432323
TI  - [Groups of passive and active control state in longitudinal experiments: an
      electrophysiological study].
AB  - Long-term electrophysiological experiments were carried out with rats with
      chronically implanted electrodes into dopaminergic brain structures. Within 4
      weeks after surgery, the relative spectral power of electrical activity in the
      delta1 and delta2 frequency bands decreased, while the relative spectral power in
      the alpha, beta1 and beta2 bands increased. A delayed (to the 4-5th week after
      surgery) increase in the total amount of sleep and REM sleep percent was observed
      in the sleep architecture of these animals. Multiple (during 2 weeks daily)
      intraperitoneal saline injections altered the dynamic of electrophysiological
      indices on the 2nd-3rd postsurgery weeks. The total sleep amount being not
      increased, the total and mean REM sleep durations increased, and the dynamic of
      the relative spectral power of electrical activity in the dopaminergic brain
      structures in the delta1, alpha and beta2 bands was found to be changed.

PMID- 17432325
TI  - How to accomplish what you want without killing yourself.

PMID- 17432326
TI  - Meeting demands of our older nurses by changing workforce environments.

PMID- 17432327
TI  - Living with macular degeneration.

PMID- 17432328
TI  - Bringing order to chemical chaos.

PMID- 17432329
TI  - Knowing when and how to take the keys away.

PMID- 17432330
TI  - Dioxin formation from waste incineration.
AB  - There has been great concern about dioxins-polychlorinated dibenzo dioxins
      (PCDDs), polychlorinated dibenzo furans (PCDFs), and polychlorinated biphenyls
      (PCBs)-causing contamination in the environment because the adverse effects of
      these chemicals on human health have been known for many years. Possible dioxin
      contamination has received much attention recently not only by environmental
      scientists but also by the public, because dioxins are known to be formed during
      the combustion of industrial and domestic wastes and to escape into the
      environment via exhaust gases from incinerators. Consequently, there is a
      pressing need to investigate the formation mechanisms or reaction pathways of
      these chlorinated chemicals to be able to devise ways to reduce their
      environmental contamination. A well-controlled small-scale incinerator was used
      for the experiments in the core references of this review. These articles report
      the investigation of dioxin formation from the combustion of various waste
      simulated samples, including different kinds of paper, various kinds of wood,
      fallen leaves, food samples, polyethylene (PE), polystyrene (PS), polyvinyl
      chloride (PVC), polyvinylidene chloride, polyethylene tetraphthalate (PET), and
      various kinds of plastic products. These samples were also incinerated with
      inorganic chlorides (NaCl, KCl, CuCI2, MgCl2, MnCl2, FeCl2, CoCl2, fly ash, and
      seawater) or organic chlorides (PVC, chlordane, and pentachlorophenol) to
      investigate the role of chlorine content and/or the presence of different metals
      in dioxin formation. Some samples, such as newspapers, were burned after they
      were impregnated with NaCl or PVC, as well as being cocombusted with chlorides.
      The roles of incineration conditions, including chamber temperatures, O2
      concentrations, and CO concentrations, in dioxin formation were also
      investigated. Dioxins (PCDDs, PCDFs, and coplanar-PCBs) formed in the exhaust
      gases from a controlled small-scale incinerator, where experimental waste samples
      were burned, were analyzed by gas chromatography/mass spectrometry. Formation of
      total PCDFs was much higher than that of PCDDs in all samples. The total PCDFs
      comprised 70%-90% of the total dioxin formed. The amount of total PCDFs formed
      ranged from 0.78 ng/g (newspaper) to 8,490ng/g (PVC burned in high CO
      concentration). The amount of total PCDDs formed ranged from 0.02ng/g (newspaper)
      to 430ng/g (PVC). Coplanar PCBs were found at the lowest level of the dioxins
      formed. Their formation levels ranged from 0ng/g (newspaper) to 77.6ng/g (PVC).
      It is obvious that the samples with either inorganic or organic chlorides
      produced much more dioxins than the sample without chlorides when incinerated
      under similar conditions. It is not clear how inorganic and organic chloride
      contribute differently to dioxin formation. Among the metals examined, copper
      seems to have higher activity toward dioxin formation than other metals. It acted
      not only as a catalyst but also as a transmitter of heterogeneous chlorine. The
      toxicity equivalence quantity (TEQ) values generally correlated with the amount
      of chlorine content in the samples and the amount of dioxin formed in exhaust
      gases from an incinerator. When the same sample was incinerated at different
      temperatures, however, the sample burned at low temperature yielded a higher TEQ
      value than did the sample burned at high temperature. The samples that did not
      contain chlorine or were not combusted with chlorides exhibited low TEQ values.
      In contrast, samples with high chlorine content, such as PVC (51.3%), gave high
      TEQ values. Combustion temperatures may play an important role in dioxin
      formation in exhaust gases from the incineration of waste materials. However, no
      significant relationship between dioxin formation and chamber temperatures was
      reported in the core articles. However, It is obvious that dioxin formation
      occurred at temperatures above 450'C and was reduced significantly at
      temperatures above 850 degrees C. The reaction occurring in an incinerator is
      extremely complex, and there are many factors in addition to combustion
      temperature influencing dioxin formation. Even though it is possible to
      hypothesize reasonable formation mechanisms of dioxins produced in exhaust gases
      according to the results obtained from experiments in classical chemistry, the
      reactions involved in an incinerator are extremely complex and heterogeneous.
      More detailed investigation of the many individual factors influencing dioxin
      formation is needed to find ways to reduce their formation in individual and
      municipal incinerators.

PMID- 17432331
TI  - Coca and poppy eradication in Colombia: environmental and human health assessment
      of aerially applied glyphosate.
AB  - The production of coca and poppy as well as the processing and production of
      cocaine and heroin involve significant environmental impacts. Both coca and poppy
      are grown intensively in a process that involves the clearing of land in remote
      areas, the planting of the crop, and protection against pests such as weeds,
      insects, and pathogens. The aerial spray program to control coca and poppy
      production in Colombia with the herbicide glyphosate is conducted with modern
      state-of-the-art aircraft and spray equipment. As a result of the use of best
      available spray and navigation technology, the likelihood of accidental off
      target spraying is small and is estimated to be less than 1% of the total area
      sprayed. Estimated exposures in humans resulting from direct overspray, contact
      with treated foliage after reentry to fields, inhalation, diet, and drinking
      water were small and infrequent. Analyses of surface waters in five watersheds
      showed that, on most occasions, glyphosate was not present at measurable
      concentrations; only two samples had residues just above the method detection
      limit of 25 microg/L. Concentrations of glyphosate in air were predicted to be
      very small because of negligible volatility. Glyphosate in soils that are
      directly sprayed will be tightly bound and biologically unavailable and have no
      residual activity. Concentrations of glyphosate plus Cosmo-Flux will be
      relatively large in shallow surface waters that are directly oversprayed (maximum
      instantaneous concentration of 1,229microgAE/L in water 30cm deep); however, no
      information was available on the number of fields in close proximity to surface
      waters, and thus it was not possible to estimate the likelihood of such
      contamination. The formulation used in Colombia, a mixture of glyphosate and
      Cosmo-Flux, has low toxicity to mammals by all routes of exposure, although some
      temporary eye irritation may occur. Published epidemiological studies have not
      suggested a strong or consistent linkage between glyphosate use and specific
      human health outcomes. An epidemiology study conducted in Colombia did not show
      any association between time to pregnancy in humans and the use of glyphosate in
      eradication spraying. The mixture of glyphosate and Cosmo-Flux was not toxic to
      honeybees. The mixture was, however, more toxic to the alga Selenastrum, the
      cladoceran Daphnia magna, fathead minnow, and rainbow trout than formulated
      glyphosate (Roundup) alone. Studies on the use of glyphosate in agriculture and
      forestry have shown that direct effects on nontarget organisms other than plants
      are unlikely. Indirect effects on terrestrial arthropods and other wildlife may
      be the result of habitat alteration and environmental change brought about by the
      removal of plants by glyphosate. Because of the lack of residual activity,
      recovery of glyphosate-treated areas in Colombia is expected to be rapid because
      of good plant growth conditions. However, return to the conditions of tropical
      old-growth forest that existed before clear-cutting and burning may take hundreds
      of years, not from the use of glyphosate but because of the clear-cutting and
      burning, which are the primary cause of effects in the environment. The risk
      assessment concluded that glyphosate and Cosmo-Flux did not present a significant
      risk to human health. In the entire cycle of coca and poppy production and
      eradication, human health risks associated with physical injury during clear
      cutting and burning and the use of pesticides for protection of the illicit crops
      were judged to be considerably more important than those from exposure to
      glyphosate. For the environment, direct risks from the use of glyphosate and
      Cosmo-Flux to terrestrial mammals and birds were judged to be negligible.
      Moderate risks could occur in aquatic organisms in shallow surface waters that
      are oversprayed during the eradication program. However, the frequency of
      occurrence and extent to which this happens are unknown as data on the proximity
      of surface waters to coca fields were not available. Considering the effects of
      the entire cycle of coca and poppy production and eradication, clear-cutting and
      burning and displacement of the natural flora and fauna were identified as the
      greatest environmental risks and are considerably more important than those from
      the use of glyphosate for the control of coca and poppy.

PMID- 17432332
TI  - A tough question about mental illness.

PMID- 17432333
TI  - Impossible patient? It may be borderline personality disorder.

PMID- 17432334
TI  - Religion and mental illness: safe spirituality or risky religious intervention?

PMID- 17432335
TI  - Good spiritual care: befriending the mentally ill.

PMID- 17432336
TI  - Even Christian women get depressed: how can we help?

PMID- 17432337
TI  - Compassion or pity?

PMID- 17432338
TI  - Something more: presence in nursing practice.

PMID- 17432340
TI  - The last resort?

PMID- 17432339
TI  - Are we speaking the same language?

PMID- 17432341
TI  - Cultural sensitivity: beyond first impressions.

PMID- 17432342
TI  - Dew drops and gentle rain.

PMID- 17432343
TI  - A pain scale from scripture.

PMID- 17432344
TI  - An unexpected Easter blessing.

PMID- 17432345
TI  - Is forgiveness important in spiritual care?

PMID- 17432346
TI  - [Scientific evidence-based approach and development--a review of the task of
      rhinology].

PMID- 17432347
TI  - [Preservation or reconstruction of uncinate process in endoscopic sinus surgery].
AB  - OBJECTIVE: To explore a new approach for paranasal sinus by using transnasal
      endoscope, which would be more coincided with the physiological characteristics
      of nasal cavity and nasal sinuses, and meet the requirement of structure
      reconstruction in functional nasal endoscopic surgery. METHODS: Thirty patients
      with chronic rhinosinusitis (CRS) were selected as clinical subjects. For each
      patient, the left side was selected to preserve or reconstruct the shape of
      uncinate process by nasal sinus opening surgery, the right was received
      traditional functional endoscopic sinus surgery (FESS) as control. The curative
      effect after surgery was evaluated according to the restoration of symptoms and
      local state under endoscope. The most important was to observe whether the above
      structure could restore to normal after preserving or reconstructing the shape of
      uncinate process and affect the drainage of related sinuses, and whether diseased
      sinuses could gain the similar near prognosis to that after FESS. RESULTS: The
      patients were followed up after 6 months since the performance of surgery. (1)
      Uncinate process maintained original or normal anatomical shape and did not
      affect the drainage of sinuses. (2) Opened nasal sinuses and rises were covered
      by uncinate process. (3) All sinuses drained well, and the restoration time and
      state of both sides of sinus mucosa were the same, and no local morphology was
      affected by preserving uncinate process. CONCLUSIONS: (1) Sinus opening surgery
      by preserving or reconstructing uncinate process could maintain or reconstruct
      the original nasal cavity structure, and could protect the opened sinuses and
      avoid the attack of direct airflow. (2) 6-12 months after surgery, no difference
      was found as to the self sensation about the improvement of symptoms, and the
      shape of operational cavity in experimental group was similar to that in control
      group. (3) This surgical approach was under exploration, and it was only suitable
      for CRS patients with basic normal shape of uncinate process, and the surgical
      indications would be gained depending on the advancement of technology and
      accumulation of experience and the data obtained in future curative effect.

PMID- 17432348
TI  - [Endoscopic endonasal surgery for clival tumor].
AB  - OBJECTIVE: To review our experience with endoscopic endonasal approach for
      surgical management of clival tumors. METHODS: Twenty-four patients with clival
      tumors treated by endoscopic endonasal surgery between August 2002 and November
      2005 were studied prospectively. The operative technique was described in detail.
      There were 5 chordoma, 2 ossifying fibroma, 1 meningioma, 1 craniopharyngioma, 1
      hemangioblastoma, 6 squamous cancer, 2 chondrosarcoma, 2 chondrosarcoma, 1
      lymphoma, 1 malignant giant cell tumor and 2 metastatic carcinoma. RESULTS: Total
      tumor removal was obtained in 22 cases, subtotal removal in 2 case. Follow-up
      ranged 12 to 51 months. Three patients dead. Five patients with total removal
      recurred, one of them dead. Two patients with subtotal removal dead, one with
      chondrosarcoma and one with chordoma. The complications included subarachnoid
      hemorrhage in 1 patient, and transient cerebrospinal leakage in 2 cases.
      CONCLUSIONS: The use of nasoendoscopy to perform clival tumor surgery is not only
      limited to the minimally invasive aspect, it also provides better visualization
      of deeper structures in the skull base, provides the ability to 'look around
      corners' and wide exposed field. This approach permits us to manage clival
      lesions properly.

PMID- 17432349
TI  - [Diagnosis and endoscopic treatment of sphenoid mycetoma].
AB  - OBJECTIVE: To investigate the presenting symptoms and signs, endoscopic findings,
      imaging changes and the clinical outcomes of endoscopic surgery in 23 patients
      with sphenoid mycetoma. METHODS: The clinical data and the follow-up results of
      endoscopic surgery in 23 patients with sphenoid mycetoma, between April 2001 and
      January 2006, were retrospectively analysed. RESULTS: The study population
      included 15 women and 8 men with a median age of 52.7 years. Presenting symptoms
      included headache (13 cases, 57%) and bloody discharge (9 cases, 48%). The
      computed tomography scans showed high density shadow in all 23 cases, with 17
      cases (74%) had plaque or cord shaped calcification. All patients were treated by
      endoscopic transnasal approach. No surgical complications were found. Follow-up
      ranged 3-18 months, all symptoms disappeared, except strabismus in one case after
      7 months of operation. The mucosa in surgical cavity is good. CONCLUSIONS: The
      most common clinical symptoms of sphenoid mycetoma are headache and bloody
      discharge. Computed tomography scan has great value for the diagnosis of sphenoid
      mycetoma. The minimal invasion and the good outcome are the main advantages of
      the endoscopic surgery.

PMID- 17432350
TI  - [Correlation between mucosa inflammation and abnormal drainaging state of
      maxillary sinus after endoscopic sinus surgery].
AB  - OBJECTIVE: This study is aimed to observe the natural draining state of maxillary
      sinus, to search for the key draining location (KDL) in the natural ostium, to
      investigate the relation between maxillary sinus draining and sinus inflammation,
      and to guide the treatment of maxillary sinus opening in endoscopic sinus surgery
      (ESS). METHODS: Methylene blue was used as tracer agent in this study. Fifteen
      cases with or without light maxillary sinus inflammation (without any treatment)
      were selected to observe the natural draining state and the key draining location
      in maxillary sinus fontanel. Eighty-nine cases with chronic rhinosinusitis, but
      without nasal polyp, were selected, of which the maxillary sinus mucosa restored
      well 6 months after ESS, to observe the draining state and modes in maxillary
      sinus. All patients were followed up for 12 months to evaluate the inflammation
      state of mucosa, and to analyze the relations between the draining mode and
      mucosa inflammation. RESULTS: The KDL for maxillary sinus was located in the
      posterior-inferior portion of the natural ostium, close to the attachment of
      caudal end of the uncinate process. The draining flowed along it from maxillary
      sinus to nasopharynx. After conventional transnasal endoscopic operation, 15
      cases showed relatively normal drainage, others displayed abnormal state and
      mode,including reverse draining (maxillary sinus-ethmoid sinus) , multiphase
      draining (outflow from front, back and lower wall of natural ostium), draining
      failure (with cilia transporting function of maxillary epithelium mucosae),
      cistern like change (maxillary sinus and ethmoid sinus formed one operation
      cavity, secretion accumulated in maxillary sinus) and mucosa disfunction (loss of
      cilia transporting function of maxillary epithelium mucosae). Inflammation was
      observed in 33.7% of the patients 12 months after ESS, especially in those with
      mucosa disfunction, draining failure and reverse draining. CONCLUSIONS: The KDL
      for maxillary sinus may be located in the posterior-inferior portion of the
      natural ostium, close to the attachment of caudal end of the uncinate process,
      and the drainage mode is not affected by gravity and posture. The KDL lesion
      after ESS results in abnormal draining of maxillary sinus, and excessively large
      maxillary sinus opening may aggravate mucosa inflammation of maxillary sinus. The
      abnormal draining state and mode may be related with the incidence of mucosa
      inflammation after operation. Preserving caudal end of uncinate process and
      avoiding injury of KDL would be beneficial to the restoration of mucosa and
      lessen the incidence of inflammation recurrence.

PMID- 17432351
TI  - [Severe complications in the treatment of chronic rhinosinusitis and nasal polyps
      with endoscopic sinus surgery].
AB  - OBJECTIVE: To investigate the classification, incidence and influential factors
      of severe complications occurred in endoscopic sinus surgery (ESS) and how to
      deal with them. METHODS: One thousand and one hundred two patients with chronic
      sinusitis and nasal polyps treated by ESS were analyzed. RESULTS: Twenty-one
      patients had severe complications. The types of complication included
      intraorbital hematoma (n=3), medial rectus injury (n=2), blindness (n=1),
      intracranial, hematoma (n=1), cerebrospinal rhinorrhea (n=3), nasolacrimal duct
      injury (n=3), nasal septum perforation (n=2), hemorrhage (n=2), thrombosis in
      legs (n=2) and asthma (n=2). The total incidence of severe complications was
      1.91% (21/1102), most of which were complications in orbit (0.54%) and cranium
      (0.36%). The extent of the lesion, the surgical history of the patients, the
      technique and experience of the surgeons were the most important influential
      factors to severe complications. CONCLUSIONS: Although there are many influential
      factors to severe complications in ESS, subjective factors are the more
      important, especial, the technique and the experience of the surgeon.

PMID- 17432352
TI  - [Intra-nasal scanning of tumors in nasal cavity and paranasal sinus with
      endoscopic ultrasonography].
AB  - OBJECTIVE: To evaluate endoscopic ultrasonography for masses in nasal cavity and
      paranasal sinus. METHODS: Under the guidance of nasal endoscope, sonographic scan
      of 18 masses within nasal cavity and paranasal sinus was performed by using 10
      MHz catheter transducer with diameter of 3.3 mm under local anesthesia. Twelve of
      them were benign tumors and 6 of them were malignant ones, which were confirmed
      by pathological examination of resected specimens. RESULTS: Under the guidance of
      nasal endoscope, masses could be observed accurately with catheter transducer. On
      gray scale ultrasound, most masses were heterogeneous hypoechoic, tumors with
      rich blood vessels were lower hypoechoic, and some showed irregular anechoic area
      due to dilated vascular net. Neurofibroma was with well-defined and regular
      border and entire capsule; chordoma was without distinct edge and capsule. A
      giant pituitary tumor eroding bone of sphenoid sinus and intruding into nasal
      cavity. The relationship between mass and internal carotid artery could be
      demonstrated using color Doppler flow imaging (CDFI). Blood flowing signals in
      masses could be detected by CDFI, and spectral Doppler could discriminate
      arterial or venous blood flowing signals and measure its velocity. The rich blood
      supply was observed in fibroangioma, the rich flow signals and high velocity
      could be detected in malignant tumors. CONCLUSIONS: Nasal endoscope-guided
      sonography for soft tissue masses in nasal cavity is of exact location, clear
      image and high resolution, which can reveal blood flow signals sensitively,
      differentiate arterial and venous blood signals and measure the velocity of them.
      It provides a new imaging modality for masses within nasal cavity, sinuses and
      skull base.

PMID- 17432353
TI  - [Analysis of prognostic factors in microsurgery of intratemporal facial nerve
      schwannoma].
AB  - OBJECTIVE: To discuss prognostic factors in microsurgery of intratemporal facial
      nerve schwannoma. METHODS: Clinical and follow-up materials from 13 cases of
      facial nerve schwannoma were analyzed retrospectively. Spearman rank-order
      correlation and nonparametric Mann-Whitney U test from SPSS 10.0 for Windows was
      used for the analysis. RESULTS: Each of 13 cases was operated on using modern
      microsurgery. Eleven cases among them received facial nerve reconstruction. One
      of the 13 cases lost follow-up. Others had no residue or recurrence. The House
      Brackmann grades of the cases received facial nerve reconstruction were II
      through V. Spearman rank-order correlation showed the postoperative facial nerve
      function was correlated with the preoperative duration of facial nerve paralysis
      (r = 0.925, P = 0.000) and the preoperative facial nerve function(r = 0.712, P =
      0.021). Mann-Whitney U test showed that the tumor position had no effect on the
      postoperative facial nerve function (P = 0.889). CONCLUSIONS: Among most of the
      patients who received microsurgery of facial nerve schwannoma, facial nerve
      functions could be restored to great extent. The longer the preoperative duration
      of facial nerve paralysis or the worse the preoperative facial nerve function,
      the worse the postoperative facial nerve function in cases who received facial
      nerve resection and reconstruction. Facial nerve reconstruction was helpful for
      the patient with facial nerve schwannoma whose facial muscles were denervated but
      have fibrillation potentials, as well as for the patient whose facial nerve
      schwannoma intruded internal acoustic canal.

PMID- 17432354
TI  - [Hearing evaluation of infants failed in hearing screening].
AB  - OBJECTIVE: To analyze the confusing factors and clinical and audiological
      characteristics in infants failed in hearing screening. METHODS: Between August
      2004 and January 2006, 166 infants (315 ears) with detailed birth record and
      hearing screening record were reviewed in the study. The age of this series
      ranged from 2 to 6 months. They were born in maternal and child health hospitals
      (MCH) in Guangzhou city and surrounding areas, and had hearing screened by
      otoacoustic emissions (OAE). However, they failed in the first and second hearing
      screening. The birth history, high-risk factors of hearing-impaired during
      newborn period and pregnancy history of subjects were fully detailed. Subjects
      were classified according to the age: 2 to 3 months old infants were considered
      as group 1, while 4 to 6 months old infants were considered as group 2. Auditory
      brainstem response (ABR), distortion product otoacoustic emissions (DPOAE) and
      acoustic immittance measurement were examined. Subjects with abnormal hearing
      evaluation were retested during the following one to three months (before 6-month
      old). The ABR results, DPOAE results and tympanic cavity pressure and static
      compliance value were compared between the two tests and then diagnosis was made.
      RESULTS: (1) Among the 166 cases, 34 (20.5%) cases were once suffered from
      hypercholesterolemia of newborn, and 10 cases (6.0%) had asphyxia and hypoxia
      history. (2) The proportion of presenting type B tympanogram in group 2 was
      higher than that of group 1 (chi2 = 26.22, P < 0.01). (3) The proportion of
      normal ABR in group 2 (37.2%) was significantly higher than that of in group 1
      (23.4%, chi2 = 0.527, P < 0.05). Fifty-six percent of infants accepted twice ABR
      test had improving ABR results during the second test. (4) The proportion of
      normal DOPAE in group 2 (39.7%) was slightly lower than that of in group 1
      (42.2%, chi2 = 0.14, P > 0.05). Among the infants who accepted twice DPOAE test,
      32.0% had improving results in the second test. (5) Four cases (4 ears ) were
      diagnosed as auditory neuropathy. CONCLUSIONS: Middle ear function and
      development of auditory system in infants may be confusing factors in hearing
      screening. The results of hearing screening should be interpreted appropriately.

PMID- 17432355
TI  - [Cranial schwannomas of jugular foramen].
AB  - OBJECTIVE: To investigate the diagnosis and surgical treatment of lower cranial
      schwannomas of jugular foramen. METHODS: Retrospective review of 11 cranial
      schwannomas of jugular foramen which received surgical removal from November 2001
      to June 2005. According to classification, 5 cases were as intracranial type, 3
      as jugular foramen type, 1 as neck extension type and the other 2 as combination
      type. Surgical procedures composed of 3 translabyrinthine, 2 retrosigmoid and 6
      subtemporal fossa approach. RESULTS: One-stage total tumor removal was
      accomplished in all the cases without any severe complications. Residue hearing
      was preserved in two cases received retrosigmoid approach. Anatomic completion of
      facial nerve was maintained in all the cases. Lower cranial neuropathy was found
      in 9 cases before surgery and occurred in all the cases after surgery. During in
      hospital period complete compensation of swallowing ability was gained in 7
      cases, near total, partial compensation and total decompensation was found in 1,
      2 and 1 cases, respectively. Followed-up for 6 months, 10 cases caught normal
      swallowing function while the other one with partial compensation. Hoarseness was
      occurred in all the cases immediately after surgery and improved during follow
      up. CSF leakage was occurred in 2 cases, no intracranial infection was found in
      all the cases. CONCLUSIONS: Surgical treatment was the optimal management to
      cranial schwannoma of jugular foramen. Surgical approach selections depends on
      tumor classification on magnetic resonance imaging features. Nerve protection in
      surgery and postoperative rehabilitation were the key to better prognosis.

PMID- 17432356
TI  - [Cultivation, identification and ultrastructural observation of the proliferative
      cells from the newborn rat cochlea].
AB  - OBJECTIVE: To explore whether there could be proliferative cells in the cochlea
      of the newborn rat or not and what kinds of cells should be differentiated from
      the proliferative cells while to study the effect of the growth factors on the
      proliferative cells and the ultrastructure of the proliferative cells. METHODS:
      The Corti's organ were dissected from the cochlea of newborn SD rats and
      cultured. The proliferative condition of cells was tested by infusing the 5-bromo
      2-deoxyuridine (BrdU) into the culture medium. And the variety of the spheres and
      differentiated cells were identified by immunohistochemistry. Corti's organ from
      forty-eight surface preparations was randomly divided into 4 groups: control
      group; epidermal growth factor (EGF) group; basic fibroblast growth factor (bFGF)
      group and EGF + bFGF group, with each group including 12 Corti's organ, and then
      the number of cell spheres of each Corti's organ was counted. The data was
      statistically analysed with ANOVE. Finally, the proliferative cells were observed
      under scanning electron microscope and transmission electron microscope. RESULTS:
      (1) The cell spheres can be observed in the cell culture of the Corti's organ. In
      present experiment, 90.1% of cells in spheres were labeled by BrdU, while nestin
      of spheres, the marker of hair cells--myosin 7A, espin, and phalloidin of the
      differentiated cells were positive. The marker of neuron-microfilament-M was also
      positive, and some differentiated cells were labeled by myosin 7A and BrdU, espin
      and BrdU, NF-M and BrdU at the same time. (2) The average number (x +/- s) of
      spheres from single Corti's organ was: 45.3 +/- 23.00 in control group, 86.2 +/-
      34.1 in EGF group, 96.5 +/- 33.6 in bFGF group and 131.2 +/- 47.00 in EGF + bFGF
      group. There were significant differences between other groups respectively (P <
      0.05) but there was no significant differences between EGF group and bFGF group
      (P > 0.05). (3) Scanning electron microscopy and transmission electron microscopy
      showed that cells of the spheres were round and had the same size and many short
      and thin microvilli on the surface of these cells. The cytoplasm were rich of
      organellae such as endoplasmic reticulum, mitochondrion, and cytoskeleton such as
      microfilament, microtube, et al. Tight junction, desmosomes and gap junctions
      between two adjacent cells were seen. CONCLUSIONS: The proliferative cells are
      observed in the cochlea of the newborn rats and proliferative cells could
      differentiated into hair cells with bundles-like structure and neuron. Both EGF
      and bFGF possess the promoting effects for proliferation on the proliferative
      cells while the proliferative cells have characters of earlier immature cells.

PMID- 17432357
TI  - [Electrophysiological characteristics of muscarinic cholinergic receptor in rat
      medial vestibular nucleus neurons by visual patch clamp technique].
AB  - OBJECTIVE: To establish the visual patch clamp whole-cell recording technique and
      study the properties and functional significance of muscarinic receptor-mediated
      currents in rat medial vestibular nucleus neurons (MVNn). METHODS: Brain slices
      containing the MVN were prepared from fifteen Wistar rats. By combining infrared
      differential interference contrast (IR-DIC) technique and CCD-Camera system with
      visual patch clamp whole-cell recording technique, twenty healthy neurons were
      located and muscarinic receptor-mediated currents in rat MVNn were observed and
      analyzed. RESULTS: Visual patch clamp technique can be used to make direct
      localization and to make sure of active neuron. In MVNn, a comparison of the
      current-voltage relationships before and during the application of muscarine,
      which revealed an increase in the slope of the I-V curve and the reversal
      potential for this response lay at (-88.4 +/- 4.9) mV (x +/- s), indicates that
      the activation of muscarinic cholinergic receptors leads to a decrease in
      potassium current. The test in the voltage sensitivity of the muscarine-induced
      response, which showed that the effect had a linear current-voltage relationship
      and reversed at (-86.7 +/- 3.5) mV, indicates that the potassium current blocked
      by muscarine corresponds to the voltage-insensitive leak potassium current.
      CONCLUSIONS: Visual patch clamp technique, which was considered better than blind
      patch clamp technique, can improve the success of sealing process. By the
      analysis of muscarinic receptor-mediated currents, the data provide support that
      muscarinic cholinergic mechanisms play a prominent role in the modulation of the
      excitability of MVNn and also offer a new idea for the efficacy of
      anticholinergic drugs.

PMID- 17432358
TI  - [Pathologic changes of palatopharyngeal muscle in patients with obstructive sleep
      apnea hypopnea syndrome].
AB  - OBJECTIVE: To study the pathologic changes of the palatopharyngeal muscles in
      patients with obstructive sleep apnea hypopnea syndrome (OSAHS), the role of the
      above muscles in OSAHS pathogenesis was discussed. METHODS: Thirty OSAHS patients
      receiving uvulopalatopharyngoplasty selected, and ten normal subjects without
      snoring as the control group. The successive longitudinal sections of
      palatopharyngeal muscle were stained for observing Troponin-I's content. All
      specimens were examined with transmission electronmicroscopy (TEM) and light
      microscopy. RESULTS: Twenty nine of 30 specimens obtained from OSAHS patients
      evaluated with TEM showed pathologic changes of different degrees. While 2 among
      10 specimens in control group showed mild myofibril edema or hypertrophy, no
      pathologic changes shown in other specimens. Immunohistochemistrial results of
      all specimens sections stained for observing Troponin-I antibody have shown that
      negative grey degree value is 146.30 +/- 10.72 in study group and 107.50 +/- 4.81
      in control group respectively. There is significant difference between these two
      groups (P < 0.05). The negative grey degree value of study groupl and study
      group2 are 143.12 and 148.80 respectively , no statistical difference (P > 0.05).
      CONCLUSIONS: Palatopharyngeal myelofibrosis may affect pharyngeal dilator muscles
      function, this could be one mechanism of upper airway collapsibility.

PMID- 17432359
TI  - [Effects of sodium butyrate on growth, apoptosis and telomerase activity in Hep-2
      cells].
AB  - OBJECTIVE: To study the effects of sodium butyrate (SB) on growth, apoptosis and
      telomerase activity in Hep-2 cells. METHODS: Growth inhibition effect of SB on
      Hep-2 cells was assessed by methyl thiazolyl tetrazolium (MTT) assay.
      Morphological alterations were observed by electronic microscope. Cell apoptosis
      was confirmed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling (TUNEL) method, DNA fragmentation and flow cytometry (FCM). Cell cycle
      was analyzed by FCM. Telomerase activity was examined by telomeric repeat
      amplification protocol (TRAP)-silver staining. The expression status of
      telomerase subunits was analyzed by reverse transcription-polymerase chain
      reaction (RT-PCR). RESULTS: A time-and dose-dependent inhibition was detected in
      cells treated with SB. Typical morphological changes of apoptotic cells were
      observed under electronic microscopy. The characteristic DNA fragmentation of
      apoptotic cells was detected by agarose gel electrophoresis. Apoptosis and the
      changes of cell cycle were confirmed by TUNEL method and FCM. The apoptosis
      indexes of the cells before treatment and at 72 h after SB (2.5 mmol/L) treatment
      were 2.27 +/- 1.18 and 33.50 +/- 2.75 respectively, the apoptosis rates were 2.
      86% and 31. 28% respectively, the proportion of the cells at G0/G1 stage were
      50.38% and 70.88% respectively, the proportion of the cells at S stage were
      27.40% and 8.20% respectively, and the proliferation indexes of the cells were
      49.62% and 29.12% respectively. Telomerase activity and expression level of human
      telomerase reverse transcriptase (hTERT), the key subunit of telomerase,
      decreased after SB treatment. No significant changes were observed in the
      expression of human telomerase RNA (hTR) and human telomerase associated protein
      (hTP1), the other two subunit of telomerase. CONCLUSION: SB could inhibit growth
      of Hep-2 cells and induce apoptosis in the cells, and inhibit telomerase activity
      by decrease expression level of hTERT.

PMID- 17432360
TI  - [The design and clinical application of styloidectomy].

PMID- 17432361
TI  - [Clinical value of 18FDG-PET in diagnosing and detecting residue or recurrence of
      nasopharyngeal carcinoma].

PMID- 17432362
TI  - [Bilateral laryngeal granulomas after endotracheal intubation].

PMID- 17432363
TI  - [Non-Hodgkin's lymphoma in the subglottic region and the trachea].

PMID- 17432364
TI  - [The commonly used scales for measuring quality of life in patients with rhinitis
      and sinusitis].

PMID- 17432365
TI  - [Advances in the medical and surgical treatment of chronic rhinosinusitis].

PMID- 17432366
TI  - Diana children's nurses deserve recognition for their vital work.

PMID- 17432367
TI  - A lesson in quitting.
AB  - A Cornish health visitor and a school nurse adviser are helping schoolchildren
      stop smoking using innovative approaches.

PMID- 17432368
TI  - Clinical confidence.
AB  - Clinical knowledge summaries on how to manage almost 500 clinical scenarios give
      up-to-date information on the 'what, why and how' of best treatments.

PMID- 17432369
TI  - Alcohol is the true 'rape drug'.

PMID- 17432370
TI  - Delirium part one: clinical features, risk factors and assessment.
AB  - Delirium is a common and under-reported problem in older adults. A lack of
      consensus over the terminology used to describe delirium may contribute to its
      underdiagnosis, and a number of predisposing factors are linked to it. This
      article, the first of two, aims to define delirium, describe the different types
      and identify risk factors associated with its development. Delirium is an
      important condition as it has a deleterious effect on patient outcomes and
      quality of life if it is not detected early and managed effectively. The
      detection of delirium and a variety of assessment tools are also considered. Part
      two, to be published in next week's Nursing Standard, examines the nursing
      management of delirium.

PMID- 17432371
TI  - Acute urinary retention: causes, clinical features and patient care.
AB  - This article provides an overview of acute urinary retention (AUR), which can
      cause patients severe pain and distress. It examines potential causes and risk
      factors. The main strategies for the treatment and clinical management of
      patients are discussed. Nurses have a key role in identifying patients at risk of
      AUR. Therefore, the nursing role in assessment and management is explored.

PMID- 17432372
TI  - Intermittent self-catheterisation: teaching the skill to patients.
AB  - Intermittent self-catheterisation (ISC) is not a new concept. However, it is a
      method that could be more widely used by patients to drain the bladder rather
      than having an indwelling catheter with a drainage bag and its associated
      problems. The author describes the procedure, patient assessment, and the
      training required by patients so that they can undertake ISC. Self
      catheterisation promotes patient independence, improves quality of life and helps
      to avoid complications associated with indwelling urinary catheters.

PMID- 17432373
TI  - Chronic kidney disease.

PMID- 17432374
TI  - Emergency medicine.

PMID- 17432375
TI  - The good portfolio.

PMID- 17432376
TI  - Pressure is no excuse.

PMID- 17432377
TI  - Floc size distributions in dissolved air flotation of Winnipeg tap water.
AB  - A bench-scale continuous flow dissolved air flotation (DAF) system was operated
      using Winnipeg tap water. Three different dosages of alum were applied: 41.7 mg
      l(-1), 25.5 mg l(-1) and 15.5 mg l(-1). Floc size distributions formed at
      different coagulant dosages were analyzed to identify characteristics of floc
      size distribution optimal for flotation. Alum dose of 25.5 mg l(-1) was found to
      be optimal for the bench scale DAF unit in this study. At this dosage, the DAF
      effluent achieved a turbidity of 0.25 NTU and color of 3.8 TCU, significantly
      lower than that for the tap water. The optimum floc size distribution at the dose
      of 25 mg l(-1) had the logarithmic mean size of 27 microm which was close to the
      size of air bubbles produced by the saturator in this study (30 microm). The
      results of this study suggest that the DAF treatment process is optimized when
      the logarithmic mean floc size and bubble size are equal.

PMID- 17432378
TI  - A model for the simulation of the SHARON process: pH as a key factor.
AB  - The SHARON process allows partial nitrification of wastewaters with high ammonium
      content and, when coupled with the Anammox process, represents a more sustainable
      alternative for N-removal than a conventional nitrification-denitrification. In
      this work, a mathematical model describing a continuously aerated SHARON reactor
      is presented. Special attention was given to the pH, because it affects
      substrates availability and inhibition phenomena, implementing an algorithm for
      its calculation. Since ammonium-oxidizing and nitrite-oxidizing organisms are
      inhibited by their own substrates, ammonia and nitrous acid respectively, Haldane
      kinetics was used in both nitrification steps. A preliminary evaluation of the
      model using historical experimental data generated in a lab-scale SHARON reactor,
      fed with synthetic substrate, is also presented, corroborating that the quality
      of the obtained effluent is highly dependent on pH.

PMID- 17432379
TI  - Removal of chlorothalonil, methyl parathion and methamidophos from water by the
      Fenton reaction.
AB  - The efficiency of a dark Fenton system (H2O2/Fe2+) to remove chlorothalonil from
      water, alone and in the presence of the organophosphorous pesticides methyl
      parathion and methamidophos, was evaluated. Here we show that the process is
      rapid and efficient. Nearly complete degradation of chlorothalonil and methyl
      parathion (98%) was observed in less than 10 min whereas methamidophos showed
      similar levels of efficiency only after 40 to 90 min. Formulating agents did not
      appear to impair the degradation of active ingredients. Interactions during the
      degradation of mixtures of the three pesticides only appeared to affect
      methamidophos degradation.

PMID- 17432380
TI  - Pre-treatment of wastewater sludge--biodegradability and rheology study.
AB  - This study investigates the changes in biodegradability, rheology and metal
      concentration of wastewater sludge--non-hydrolyzed (raw), sterilized, and
      hydrolyzed (thermal alkaline pre-treatment) at total solids concentration from 10
      50 g l(-1) to ascertain the bioavailability of nutrients for subsequent
      fermentation. The dissolved solids concentration increased linearly with total
      solids. Irrespective of the wastewater sludge (raw or, pre-treated), percentage
      biodegradability in terms of total solids (26.5-44.5%), total COD (25.8-56.5%)
      and dissolved solids (41.9-66.9%) was maximum around 20 g l(-1) solids
      concentration. The pseudoplasticity of sludge decreased (consistency index
      decreased from 895.1 to 5.2 and flow behaviour index increased from 0.28 to 0.88,
      for all sludge types) with pre-treatment and increased with total solids
      concentration. The pre-treated sludge, namely, sterilized and hydrolyzed sludge
      showed higher microbial growth (1-2 log cycles increase in comparison to raw
      sludge) suggesting their susceptibility to microbial degradation. The C:N ratio
      decreased with pre-treatment (raw sludge > sterilized > hydrolyzed) during
      biodegradation. Although the metal concentration increased in incubated
      hydrolyzed sludge, the final concentration was within the regulatory norms for
      agriculture application. Thus, pretreatment of sludge resulted in increase in
      biodegradability making it an excellent proponent for fermented value-added
      products.

PMID- 17432381
TI  - Effects of hydraulic retention time (HRT) and sludge retention time (SRT) on the
      treatment of nitrobenzene in AMBR/CSTR reactor systems.
AB  - The effect of hydraulic retention time (HRT) and solid retention time (SRT) on
      the biodegradation of a synthetic wastewater containing nitrobenzene was
      investigated in a sequential anaerobic migrating blanket reactor (AMBR) and
      aerobic completely stirred tank reactor (CSTR) system. Reactor performance was
      evaluated at six different HRTs (1,1.5,2,2.5,3.5,5.19 and 10.38 days) and at six
      different SRTs (32,53,76,217,415 and 932 days). The influent COD and nitrobenzene
      concentration were kept constant at 3000 mg l(-1) and 60 mg l(-1), respectively,
      during continuous operation. The maximum COD removal efficiency was found to be
      92% at a HRT of 10.38 days and a SRT of 932 days in AMBR reactor. However,
      nitrobenzene removal efficiencies were found to be 99.9% through all HRTs and
      SRTs in AMBR reactor. Most of the influent COD and nitrobenzene concentrations
      were removed in first compartment of AMBR. The total and methane gas production
      rates increased from 2760 ml day(-1) to 11760 ml day(-1) and from 1300 ml day(-1)
      to 3331 ml day(-1), respectively, as the HRT was decreased from 10.38 to 1 day in
      AMBR. However, methane percentage decreased from 47% to 28% with decreased HRTs
      and SRTs. The methanogens inhibition was observed at lower HRTs. pH values in the
      compartments and the effluent of AMBR was between optimum values. TVFA
      concentrations in effluent of AMBR were measured as zero until a HRT of 3.5 days.
      In the aerobic CSTR reactor, the COD removal efficiency decreased from 79% to 68%
      with decreased HRT from 6.79 to 0.67 days. It was found that the nitrobenzene
      transformed to aniline under anaerobic phase, and then the aniline mineralized in
      the oxidative stage, with efficiencies varying between 79% to 99.9%, in
      anaerobic/aerobic reactor system.

PMID- 17432382
TI  - Halophilic and halotolerant bacteria from river waters and shallow groundwater
      along the Rouge River of southeastern Michigan.
AB  - The use of sodium chloride to melt highway and road snow is believed to have a
      significant effect on the groundwater ecosystem of the rivers where the salt from
      the roads drain. As the river composition changes, the bacterial population also
      changes to favour those bacteria that are more suited to the higher salt
      concentrations. In this experiment, we surveyed the cultivable salt-loving
      organisms (halophiles) on three sites that encompass the Rouge River (Lotz; site
      1, Lilly, site; 8, and Ford Field, site 9). A total of 125 isolates were
      surveyed. Representative isolates of distinct morphologies were subjected to
      physiological test, using API strips and identified by 16 rDNA sequence analysis.
      The 16S rDNA sequences were analyzed and compared with sequences from Genbank.
      Results indicated that the SSU rRNA sequences of the bacterial isolates were
      similar to six major genera, Bacillus, Staphylococcus, Halobacillus,
      Paenabacillus, Halomonas, and Clostridium. Half of the isolates sequenced were
      similar to Bacillus spp. The API assay showed that the majority of the isolates
      were positive for the enzymes tryptophane deaminase, gelatinase and beta
      galactosidase. Indole production, acetoin production and citrate utilization were
      not observed for any isolates. Fermentation of carbohydrates was observed for
      very few isolates. The primary enzyme found in all isolates was arginine
      dihydrolase, which might be an indicator of the presence of such enzyme in
      halophilic and halotolerant bacteria present in the Rouge River.

PMID- 17432384
TI  - Photochemical treatment of industrial textile effluent containing reactive dyes.
AB  - Textile effluents are a result of the use of reactive dyes which present a strong
      environmental impact. These are substances of concern when conventional treatment
      processes are to be considered. This work refers to the study of post-treatment
      (purification) of the textile effluent originating from the use of reactive dyes
      (after biological treatment for activated sludge) through photocatalysis using
      TiO2 as semiconductor. The photocatalytic process was optimised according to the
      mass of the semiconductor (1.4 g l(-1)), flow of air (150 ml s(-1)), temperature
      (55 degrees C) and time of treatment (240 min). In the optimised conditions it
      was possible to verify high efficiency in the colour reduction (92%), COD (65%),
      BOD (40%) and TOC (29.3%). The study reached the conclusion that the
      photocatalytic process presents great potential as a method of post-treatment of
      effluents derived from the textile industry.

PMID- 17432383
TI  - Screening of natural product biocides for control of non-indigenous species.
AB  - Several benzo-, naphtho- and anthraquinones were tested for their efficacy as
      biocides in controlling aquatic nuisance species in ships' ballast water. A
      requirement of this application was broad spectrum aquatic toxicity, coupled with
      a relatively rapid rate of degradation, in order to comply with coastal discharge
      requirements. Compounds were screened using a suite of toxicity bioassays
      designed to establish their relative toxicity to an array of planktonic organisms
      including larval bivalves Dreissena and Crassostrea, various developmental stages
      of the estuarine copepod Eurytemora affinis, brine shrimp larvae (Artemia
      salina), the freshwater invasive water flea Bythotrephes, larval sheepshead
      minnows CCyprinodon variegates) and two unicellular algal genera Isochrysis and
      Neochloris.. The majority of the data were recorded as the lowest concentration
      of the test compound resulting in complete mortality or inactivation of test
      organisms (LC ,m). The naphthoquinones juglone, plumbagin, menadione and
      naphthazarin showed the highest toxicity to the broadest range of organisms,
      often at levels much less than 1 mg l(-1), and most of the attention was focused
      on this group. While plumbagin and juglone appeared overall to be the most toxic
      compounds, it was concluded that menadione was probably the most cost-effective
      candidate compound for shipboard use for controlling invasive species in ballast
      water, particularly in view of the large volumes of water that would require
      treatment.

PMID- 17432385
TI  - Piggery wastewater treatment in a tropical climate: biological and chemical
      treatment options.
AB  - A novel biological treatment system was developed for the treatment of piggery
      wastewater under tropical conditions. It consisted of three consecutive sponge
      based floating biofilters. The Upflow Anaerobic/Anoxic/Aerobic Floating Filter
      (UA3FF) system was shown to be effective with carbonaceous and, particularly,
      nitrogenous matter. The rationale for the processes occurring in anoxic-aerobic
      reactors was based on the concept of nitritation-denitritation rather than
      nitrification-denitrification. The N-related microbial communities manipulated by
      changing DO concentration and hydraulic retention time were able to effect a
      considerable increase in the total and specific N-removal (70% and 0.6 kg N m(-3)
      filter media per day, respectively) as compared to data reported elsewhere.
      Fluorescence In Situ Hybridization and Polymerase Chain Reaction amplification of
      ammonia monooxygenase (amoA) gene were used to study interrelationships between N
      related microbial groups in the system. Microbiological data was interpreted in
      terms of operational behavior and performance of the reactors. The N-removal
      efficiency of the biological UA3FF system was compared with a combined
      biological/physicochemical system based on (a) biological anaerobic pretreatment
      followed by (b) a chemical precipitation (CP) and (c) an air stripping. Both
      systems were scrutinized as to operational advantages and costs. The treatment
      options could produce effluent of a high quality (202 mg COD l(-1), 126 total-N
      l(-1) and 89 mg COD l(-1) 48 total-N l(-1) in the biological and combined
      biological/physico-chemical treatment options, respectively) amenable for the
      subsequent treatment at the municipal facilities. However, the UA3FF biological
      treatment system was superior to the combined system by a factor of 20 as far as
      costs are concerned.

PMID- 17432386
TI  - Modeling of particle removal in the first coarse media of direct horizontal-flow
      roughing filtration.
AB  - Horizontal-Flow Roughing Filtration (HRF) is an alternative pretreatment method
      e.g. prior to Slow Sand Filtration (SSF). However, some of its limitations are
      that the effluent quality drops drastically at higher turbidity (>200NTU) and at
      higher filtration rate (>1 m h(-1)). To overcome these drawbacks, we suggested
      Direct Horizontal-Flow Roughing Filtration (DHRF), which is a modified system of
      Horizontal-Flow Roughing Filtration (HRF) by addition of a low dose of coagulant
      prior to filtration. To optimize the DHRF configuration, a conceptual and
      mathematical model for the coarse compartment has been developed in analogy with
      multi-plate settler. Data from simple column settling test can be used in the
      model to predict the filter performance. Furthermore, the model developed herein
      has been validated by successive experiments. The conventional column settling
      test has been found to be handy and useful to predict the performance of DHRF for
      different raw water characteristics (e.g. coagulated or uncoagulated water,
      different amounts of organic matter, etc.) and different initial process
      conditions (e.g. coagulant dose, mixing time and intensity, etc.). An optimum
      filter design for the coarse compartment (grain size 20 mm) has been found to be
      of 3m h(-1) filtration rate with filter length of 4-4.5 m.

PMID- 17432387
TI  - Batch nitrifying cultures in presence of mixtures of benzene, toluene, and m
      xylene.
AB  - Benzene, toluene, and m-xylene compounds in individual (5.0 +/- 0.5 mg C l(-1))
      and mixed solutions (2.5 +/- 0.2 mg C l(-1) for each one) in nitrifying batch
      cultures induced a decrease in the specific rates of NH4+ consumption (81 +/- 6%)
      and NO3- production (39-79%). However, after 24 h, ammonium consumption
      efficiency and conversion of consumed NH4+ -N into NO3- -N were close to 100% and
      there was no significant accumulation of nitrite in the medium. After 24 h, no
      aromatic intermediate was detected in the cultures and 50% of the mixed compounds
      was converted to acetate. The following order of biotransformation was found: m
      xylene > toluene > benzene. Transformation rate of m-xylene was 0.051 +/- 0.005 g
      C (g protein-N h)(-1) in individual and mixed solutions. When m-xylene was added,
      benzene was oxidized at a faster rate (0.051 +/- 0.005 g C (g protein-N h)(-1))
      whereas toluene at a slower rate (0.012 +/- 0.002 g C (g protein-N h)(-1)).

PMID- 17432388
TI  - Are physiotherapy and occupational therapy in stroke rehabilitation one and the
      same?

PMID- 17432389
TI  - Does three months of nightly splinting reduce the extensibility of the flexor
      pollicis longus muscle in people with tetraplegia?
AB  - BACKGROUND AND PURPOSE: The extensibility of the paralysed flexor pollicis longus
      (FPL) muscle is an important determinant of an effective tenodesis grip in people
      with C6 and C7 tetraplegia. Therapists believe that splinting can reduce the
      extensibility of the FPL muscle and thus improve hand function. However, there
      remains much controversy around the optimal position of splinting and its
      effectiveness is yet to be verified. The aim of the present study was to
      determine whether a three-month thumb splinting protocol reduces extensibility of
      the FPL muscle in people with tetraplegia. METHOD: An assessor-blinded, within
      subject, randomized controlled trial was undertaken. Twenty people with
      tetraplegia and bilateral paralysis of all thumb muscles were recruited from a
      sample of convenience. One randomly selected hand of each subject was splinted
      each night for three months. The splint immobilized the FPL muscle in a
      relatively shortened position by positioning the carpometacarpal and
      metacarpophalangeal joint of the thumb in flexion. The other hand remained
      unsplinted for the duration of the study. Carpometacarpal angle was measured with
      the application of a standardized torque by a blinded assessor at the beginning
      and end of the three-month study period. A device specifically designed for this
      purpose that stabilized the wrist and other joints of the thumb in full extension
      was used. RESULTS: No subject withdrew from the study. The three-month splinting
      protocol had a mean treatment effect on carpometacarpal joint angle of 0* (95%
      CI, -6 degrees to 6 degrees). CONCLUSION: Splinting the FPL muscle in a
      relatively shortened position each night for three months does not reduce its
      extensibility.

PMID- 17432390
TI  - Low levels of physical activity in back pain patients are associated with high
      levels of fear-avoidance beliefs and pain catastrophizing.
AB  - BACKGROUND AND PURPOSE: Fear-avoidance beliefs are important determinants for
      disability in patients with non-specific low-back pain (LBP). The association
      with self-reported level of physical activity is less known. The aim of the
      present study was to describe the level of physical activity in patients with
      chronic non-specific LBP and its relation to fear-avoidance beliefs and pain
      catastrophizing. METHOD: A cross-sectional study on 64 patients with chronic non
      specific LBP in primary healthcare. The variables measured and the questionnaires
      used were: level of physical activity (six-graded scale); activity limitations
      (Roland Morris Disability Questionnare (RDQ)); fear-avoidance beliefs (Tampa
      Scale of Kinesiophobia (TSK) 13-item and sub-scales 'activity avoidance' and
      'somatic focus'); and pain catastrophizing (Pain Catastrophizing Scale (PCS)).
      The level of physical activity was dichotomised into low and high physical
      activity. Individual median scores on the TSKandPCSscales were used to group the
      patients into different levels offear-avoidance beliefs and pain catastrophizing.
      Univariate logistic regressions were used to calculate odds ratios for having low
      physical activity. RESULTS: Patients with low physical activity had significantly
      higher scores in fear-avoidance beliefs and pain catastrophizing (p < 0.05). Odds
      ratios for low level of physical activity were between 4 and 8 (p < 0.05) for
      patients with high fear-avoidance beliefs or medium/high pain catastrophizing.
      CONCLUSIONS: This study indicates that it seems important for physiotherapists in
      primary care to measure levels of fear-avoidance beliefs or pain catastrophizing.
      In particular, the two subscales of the TSK could be of real value for clinicians
      when making treatment decisions concerning physical exercise therapy for patients
      with chronic LBP.

PMID- 17432391
TI  - Investigation of anterior knee pain after total hip replacement: a pilot study.
AB  - BACKGROUND AND PURPOSE: There is no previous research to determine if total hip
      replacement can lead to anterior knee pain. The idea for the present study came
      from clinical observation of anterior knee pain (AKP) after total hip
      replacement, and the objective was to investigate anterior knee pain after total
      hip replacement. METHOD: The study used a prospective single-system design with a
      convenience sample. Six men and seven women were assessed before and at six weeks
      after total hip replacement for the presence and degree of AKP, using a step-down
      test combined with a visual analogue scale (VAS). Measurements were also taken of
      leg length, hip and knee motion, thigh circumference and hamstring length using
      previously validated tests. RESULTS: Eight of thirteen subjects had AKP at six
      weeks post-operation. Active knee flexion was reduced post-operation (p <
      0.0007), and proximal, mid- and distal thigh circumferences were increased (p <
      0.0001). Eleven of 13 subjects demonstrated leg lengthening (p < 0.0001), and
      10/11 subjects demonstrated a reduction in passive knee flexion (p < 0.002). All
      biomechanical data were correlated against the VAS. Although none were
      statistically significant, both decreased active and passive knee flexion, and
      increased thigh circumference exhibited the greatest trend with the VAS.
      CONCLUSIONS: The results of the present study cannot be compared to other
      studies, as there are no previous studies on AKP after total hip replacement.
      Current outcome measures for total hip replacement do not measure for AKP,
      although it may potentially hinder full functional recovery. Orthopaedic surgeons
      and physiotherapists need to be aware if this is a possible complication of total
      hip replacement, and hence further research is required to test external
      validity.

PMID- 17432392
TI  - Are differences in leg length predictive of lateral patello-femoral pain?
AB  - BACKGROUND AND PURPOSE: Lateral patello-femoral pain can shorten an athletic
      career and generally decrease an individual's physical activity and functional
      level, such as preventing stair climbing and reducing the ability to rise from a
      chair. Leg length inequality is associated with patello-femoral pain. A leg
      length test that best distinguishes the difference between people who have
      lateral patello-femoral pain and those who do not would have clinical utility.
      The purpose of the present study was, first, to determine if unilateral, lateral
      patello-femoral pain was associated with the longer leg when inequality of leg
      lengths existed and, second, to determine if leg length direct measurement,
      indirect measurement or quadriceps angle (Q angle) could correctly classify
      participants according to the presence or absence of patello-femoral pain.
      METHOD: The study used an ex post facto, two-group quasi-experimental design. A
      volunteer sample of 52 participants (14 males, 38 females), ranged in age from 18
      to 52 years. Three methods were used to measure leg lengths: palpation meter
      (PALM) on anterior superior iliac spines (ASIS) while participants maintained
      centred weight-bearing position on a high resolution pressure mat; tape
      measurement from ASIS to medial malleolus (supine); tape measurement from ASIS to
      lateral malleolus (supine). Additionally, Q angle was measured in supine
      position. Patellar grind test, medial retinacular and lateral patellar palpation
      screened for patello-femoral pain. RESULTS: Logistic regression analysis
      determined correctness of membership in painful and non-painful patello-femoral
      groups. The PALM method of indirect measurement of leg length differences overall
      correctly classified approximately 83 % of the participants. Tape measure to
      medial and lateral malleoli as well as Q angle did not yield significant results.
      CONCLUSION: The results suggested that the PALM method of measuring leg length
      differences may have clinical utility in differentiating between patients who are
      likely to sustain patello-femoral pain syndrome and those who will not.

PMID- 17432393
TI  - Perceived disability, fatigue, pain and measured isometric muscle strength in
      patients with post-polio symptoms.
AB  - BACKGROUND AND PURPOSE: Several years after the acute polio illness, patients may
      develop new post-polio symptoms. The purpose of the present study was to evaluate
      patients with post-polio symptoms with regard to perceived fatigue, functional
      ability, muscle strength, pain and with regard to measured physical fitness and
      isometric muscle strength. In addition, the relationship between the results of
      these subjective and objective measurements was investigated. METHOD: This was a
      prospective cross-sectional study in which 32 patients with post-polio symptoms
      were included. Main outcome measures were the Fatigue Severity Scale (FSS), the
      Disability Rating Index (DRI), pain intensity, pain distribution, self-reported
      and measured muscle strength and oxygen uptake. RESULTS: A marked reduction in
      isometric muscle strength compared to normal data, high scores in fatigue,
      widespread pain, low oxygen uptake and difficulties in performing some daily
      activities were found. Self-reported general muscle strength, pain intensity and
      pain distribution correlated significantly with patients' perceived fatigue and
      function at the activity level. There was no significant correlation between self
      reported and measured results except for that found between isometric muscle
      strength in the legs and patients' perceived general muscle strength and oxygen
      uptake. CONCLUSIONS: Evaluation of pain intensity, pain distribution, perceived
      muscle strength, fatigue and ability to perform daily tasks reveals important
      aspects of health status in patients with post-polio symptoms. Reduction in
      isometric muscle strength was not reflected in those tests or in reported
      symptoms, and should be monitored independently using a sensitive assessment
      tool. Accurate screening of isometric muscle strength in isolated muscle groups
      contributes to therapeutic management in making a functional diagnosis at the
      level of body function and structure when designing specific training programmes
      and in motivating patients. An evaluation combining self-reports with sensitive
      muscle strength measures provide supplementary information and is appropriate for
      evaluating these patients in physiotherapy practice.

PMID- 17432394
TI  - Defining the Bobath concept using the Delphi technique. Raine: a response.

PMID- 17432395
TI  - Five-year clinical effectiveness of a two-step self-etching adhesive.
AB  - PURPOSE: The purpose of this prospective randomized controlled clinical study was
      to evaluate the clinical performance of a "mild" two-step self-etching adhesive,
      Clearfil SE, in Class V restorations after 5 years of clinical functioning.
      MATERIALS AND METHODS: Twenty-nine patients received two or four restorations
      following two randomly assigned experimental protocols: (1) a mild self-etching
      adhesive (Clearfil SE, Kuraray) was applied following manufacturer's instructions
      on both enamel and dentin (C-SE non-etch); (2) similar application of Clearfil
      SE, but including prior selective acid-etching of the enamel cavity margins with
      40% phosphoric acid (C-SE etch). Clearfil AP-X (Kuraray) was used as the
      restorative composite for all 100 restorations. The clinical effectiveness was
      recorded in terms of retention, marginal integrity, marginal discoloration,
      caries recurrence, postoperative sensitivity, and preservation of tooth vitality
      after 5 years of clinical service. The hypothesis tested was that selective acid
      etching of enamel with phosphoric acid improved retention, marginal integrity,
      and clinical microleakage of Class V restorations. RESULTS: Only one restoration
      of the C-SE non-etch group was lost at the 5-year recall. All other restorations
      were clinically acceptable. Marginal integrity deteriorated with time in both
      groups. The number of restorations with defect-free margins was significantly
      lower in the C-SE non-etch group (p = 0.0043). This latter group presented
      significantly more small incisal marginal defects on the enamel side (p =
      0.0169). Superficial marginal discoloration increased in both groups, but was
      more pronounced in the C-SE non-etch group and was related to the higher
      frequency of small incisal marginal defects. CONCLUSION: The clinical
      effectiveness of the two-step self-etching adhesive Clearfil SE remained
      excellent after 5 years of clinical service. Additional etching of the enamel
      cavity margins resulted in an improved marginal adaptation on the enamel side;
      however, this was not critical for the overall clinical performance of the
      restorations.

PMID- 17432396
TI  - Cuspal flexure of teeth with composite restorations subjected to occlusal
      loading.
AB  - PURPOSE: To measure in vitro the cuspal deflection produced by polymerization
      shrinkage and occlusal loading in mesio-occlusal (MO) and mesio-occlusal-distal
      (MOD) bonded composite restorations. MATERIALS AND METHODS: Twenty first
      premolars were studied, attaching a small crystal ball to each cusp vertex as a
      reference point for intercuspal distance measurements. MO cavities were made in
      ten premolars and MOD cavities in the other ten. Cavities were then restored with
      Syntac Single adhesive and Tetric Ceram composite in two increments. A precision
      micrometer was used to measure intercuspal distances in unaltered teeth (baseline
      distance), unaltered teeth under 150 N load, restored teeth at 5 min after
      restoration completion, and restored teeth under 150 N load. RESULTS: In the two
      study groups, both polymerization shrinkage and application of 150 N load
      produced a statistically significant change in intercuspal distance compared with
      baseline measurement. The cuspal deflection produced by 150 N load was
      statistically similar between unaltered and restored teeth, although
      polymerization shrinkage acted as a preload in the latter case (starting point
      was not baseline condition). The cuspal deflection produced by polymerization
      shrinkage and occlusal load was significantly greater in MOD than in MO
      restorations. CONCLUSION: The cuspal deflection produced by composite
      polymerization shrinkage and occlusal loading is significantly greater in MOD vs
      MO composite restorations.

PMID- 17432397
TI  - Ceramic-dentin bonding: effect of adhesive systems and light-curing units.
AB  - PURPOSE: To investigate the effect of different light-curing units and adhesive
      systems on the bonding of leucite ceramic to dentin. MATERIALS AND METHODS: Flat
      dentin surfaces were ground occlusally on human molars (n = 60). Hot-pressed
      ceramic blocks of IPS Empress (Ivoclar-Vivadent) were fabricated, air-particle
      abraded, and cleaned in distilled water. Following acid etching and silane
      treatment of ceramic, bonding procedures were performed. The teeth were divided
      into two groups according to the type of the adhesive system: (1) total-etch:
      etchant (Etch 37) and adhesive (One Step Plus); (2) self-etching: self-priming
      etchant (Tyrian SPE) and adhesiveOne Step Plus) (n = 30). Ceramic blocks were
      bonded to the dentin surfaces with dual-polymerizing resin luting cement
      (Duolink). For polymerization, the QTH (Blue Swan Digital, Dentanet) was used in
      soft-up and high-power mode, the LED (Elipar Freelight 2, 3M Espe) in exponential
      and standard mode, and the PAC (PlasmaStar, SP-2000, Monitex) in normal and ramp
      curing mode (n = 5). Following storage in distilled water for 24 h, the samples
      were thermocycled for 6000 cycles. The bonded specimens were serially sectioned
      and trimmed to hourglass shapes with approximately 1.6 +/- 0.16 mm2 cross
      sectional areas, then tested with the microtensile tester at a rate of 1 mm/min.
      Fracture surfaces (were analyzed with SEM. The data were analyzed with three-way
      analysis of variance (ANOVA). RESULTS: ANOVA revealed that adhesive systems (p <
      0.001) and light-curing units (p = 0.015) had a significant effect on bond
      strength values. Bond strength means (+/- SD) in MPa were as follows: total-etch
      system: QTH/soft-up mode = 16.2 (5.4); QTH/high power mode = 15 (5.4);
      LED/standard mode = 12.1 (3.3); LED/exponential mode = 15 (5); PAC/normal mode =
      19.3 (7); PAC/ramp-curing mode = 19.6 (7.4). Self-etching system: QTH/soft-up
      mode = 9.9 (2.1); QTH/high-power mode = 12.5 (4.3); LED/standard mode = 8.6 (2);
      LED/exponential mode = 13 (3.8); PAC/normal mode = 13.1 (3.9); PAC/ramp-curing
      mode = 8.9 (2.2). CONCLUSION: Results indicated that the conventional total-etch
      system provided more reliable bonding compared to the self-etching system. The
      PAC light-curing unit together with the total-etch adhesive system showed the
      highest mean micro-TBS values with either normal mode or ramp-curing mode.

PMID- 17432398
TI  - Composite-to-composite microtensile bond strength in the repair of a microfilled
      hybrid resin: effect of surface treatment and oxygen inhibition.
AB  - PURPOSE: To compare the 24-h microtensile bond strength of a microfilled hybrid
      composite to the same material after mechanical and/or chemical treatment and
      assess the effect of oxygen inhibition on the composite-composite bond. MATERIALS
      AND METHODS: Forty composite cylinders of Gradia Direct Anterior (GC) were
      prepared and stored 24 h prior to the following surface treatments: 50-microm
      aluminum oxide air abrasion and 37% phosphoric acid etching (group 1);
      hydrochloric acid and 6.9% hydrofluoric acid etching (group 2); diamond bur
      roughening and 37% phosphoric acid etching (group 3); diamond bur roughening
      (group 4). In all groups, Prime & Bond NT (Dentsply De Trey) was applied and
      light cured in air or under a nitrogen atmosphere, prior to layering a buildup of
      the repairing resin composite. Microtensile bond strength measurements were
      performed. Data were statistically analyzed with two-way ANOVA and Tukey's test
      (alpha = 0.05). RESULTS: The curing atmosphere did not significantly influence
      the interfacial strength (p < 0.05). Surface treatment significantly affected the
      composite-composite bond (p > 0.05). Air abrasion, regardless of curing
      atmosphere, resulted in the strongest bond (p < 0.05). The other treatments were
      comparable. CONCLUSION: Air abrasion and the application of a bonding agent offer
      satisfactory bond strengths for composite repair. The oxygen inhibition layer on
      a light-cured adhesive is not crucial to the success of the 24-h composite
      composite bond.

PMID- 17432399
TI  - Effect of oxygen inhibition of self-etching adhesives on enamel-dentin polymer
      bond.
AB  - PURPOSE: To determine effects of light curing of self-etching adhesives under
      ambient air or nitrogen on inhibition depths, enamel and dentin bond strengths,
      and marginal adaptation in dentin cavities. MATERIALS AND METHODS: The adhesives
      investigated were: AQ Bond (AQB, Sun Medical; Kyoto, Japan), iBond (IBO, Heraeus
      Kulzer; Hanau, Germany), One-Up Bond F II (OUB, Tokuyama; Tokyo, Japan), and
      Prompt L-Pop (PLP, 3M/ESPE; Seefeld, Germany). Inhibition layer thickness (ILT)
      was microscopically measured on 3 disk-shaped specimens each. Shear bond
      strengths (SBS) on enamel and dentin (n = 8) were determined after 10 min and 24
      h water storage of bonded composite specimens (Venus, Heraeus Kulzer). The
      marginal adaptation of bonded Venus restorations in cylindrical dentin cavities
      was microscopically evaluated after 10 min of specimen storage (n = 8) in water.
      The data were statistically analyzed using parametric and nonparametric ANOVA and
      post-hoc tests at p < 0.05. RESULTS: Adhesive curing under air revealed
      significant ILT (microm) differences: IBO (4) < AQB (8) < PLP (12) < OUB (23).
      Upon curing in nitrogen atmosphere, no inhibition occurred with AQB, IBO, and
      PLP, and < 3 microm for OUB. SBSs on enamel after 10 min or 24 h did not differ
      according to curing atmospheres (p > 0.05). On dentin, SBSs were higher after
      curing under N2 (p < 0.05). Irrespective of the curing atmosphere, marginal
      adaptation was good for AQB and IBO and poor for PLP; OUB revealed significantly
      smaller gaps under N2 than under air curing. CONCLUSION: Oxygen inhibition of the
      four self-etching adhesives investigated had no or only moderate effects on
      bonding efficacy to enamel and dentin.

PMID- 17432400
TI  - Influence of luting agent on the microleakage of all-ceramic crowns.
AB  - PURPOSE: In this in-vitro study, microleakage of all-ceramic crowns was evaluated
      at enamel and dentin margins. MATERIALS AND METHODS: Forty maxillary central
      incisors were randomly divided into 4 groups (n = 10). While buccal and palatal
      margins were placed on enamel, mesial and distal margins were placed below the
      cementoenamel junction. In groups 1 to 3, IPS Empress 2 crowns were luted with
      Variolink 2/Syntac Classic (group 1), Bifix DC/Solobond Plus (group 2) and
      Calibra/Prime & Bond NT combinations (group 3), respectively. In the control
      group (group 4), porcelain-fused-to-metal crowns were luted with a zinc-phosphate
      cement. All specimens were subjected to 5000 thermocycles (at 5 degrees C to 55
      degrees C; 30-s dwell time). After immersion in India ink for 48 h at 37 degrees
      C, the specimens were sectioned both buccolingually and mesiodistally. Each
      section was evaluated for microleakage under a stereomicroscope at 24X
      magnification. RESULTS: According to the Krukal-Wallis test, in all groups, there
      were significant differences in microleakage at the enamel margins (p = 0.001).
      Nevertheless, the margins finished in dentin showed no significant differences (p
      = 0.163). According to the Mann-Whitney U-test, statistically significant
      differences were observed in microleakage between groups 1 and 3 (p = 0.049),
      groups 1 and 4 (p = 0.001), groups 2 and 4 (p = 0.002), and between groups 3 and
      4 (p = 0.045) at the enamel margin. In group 1, significantly greater
      microleakage was observed at the dentin margin compared to the enamel margin (p =
      0.007). CONCLUSION: The adhesive luting technique demonstrated an excellent
      ability to minimize microleakage of all-ceramic crowns at the enamel margins.
      Water-based dentin bonding systems showed less microleakage than the water-free
      acetone-based dentin bonding system at the enamel margin.

PMID- 17432402
TI  - A 12-month clinical evaluation of composite resins in class III restorations.
AB  - PURPOSE: This paired-tooth randomized controlled prospective clinical study
      compared the clinical performance of three composite resins in Class III cavities
      after 12 months. MATERIALS AND METHODS: Three materials were evaluated: a
      microfilled composite resin (Durafill VS), a hybrid composite resin (Filtek
      Z250), and a nanofilled composite resin (Filtek Supreme). Thirty-eight patients
      having at least three Class III restorations were enrolled in this study. A total
      of 114 restorations were placed by two calibrated operators according to the
      manufacturers' instructions. The adhesive system (Clearfil SE Bond) was either
      applied according to manufacturer's instructions (CSE non-etch) or enamel margins
      were first etched with phosphoric acid (CSE etch). One week later, the
      restorations were finished and polished. Two other independent examiners
      evaluated the restorations at baseline according to the USPHS criteria and USPHS
      modified criteria for the items color match and surface appearance. The
      restoration location was taken into consideration during the analysis of each
      item. A nonparametric analysis of variance (Friedman test) and the Wilcoxon test
      were used for statistical analysis (alpha = 0.05). RESULTS: The restoration
      location did not influence the evaluated items. Filtek Z250 showed the best color
      match at baseline, and after 6 and 12 months. No significant difference in the
      item surface appearance was detected at baseline; however, after 6 and 12 months,
      Filtek Z250 showed the worst performance on this item. No significant difference
      was found between CSE non-etch and CSE etch groups. CONCLUSION: The hybrid
      composite resin showed an excellent immediate and 12-month color match, which was
      superior to the nanofilled and microfilled composites tested. On the other hand,
      the nanofilled and microfilled composites showed the best surface appearance
      after 12 months. Additional etching of the enamel cavity margins did not
      influence the clinical performance of the adhesive Clearfil SE Bond.

PMID- 17432401
TI  - Effect of post-retained composite restoration of MOD preparations on the fracture
      resistance of endodontically treated teeth.
AB  - PURPOSE: The present study aimed to compare the fracture resistance and failure
      patterns of endodontically treated premolars with MOD preparations restored using
      different material combinations. The null hypothesis postulated that there was no
      association between the fracture resistance of endodontically treated premolars
      and the resin composite materials or the post-and-core system used to build up
      the restorations. MATERIALS AND METHODS: Eighty single-rooted maxillary premolars
      were used. After endodontic treatment and preparation of MOD preparations, 8
      groups of 10 samples each were created, using the following material
      combinations: group 1 (control), flowable and microhybrid resin composites; group
      2, flowable A; group 3, flowable B; group 4, microhybrid resin A; group 5,
      microhybrid resin B; group 6, flowable B + microhybrid resin B; group 7, flowable
      A + microhybrid resin A + post A; group 8, flowable B + microhybrid resin B +
      post B. Mechanical static fracture tests were performed loading the specimens
      till fracture. RESULTS: The mean failure loads (N) were 502 (control), 470 (group
      7), 445 (group 8), 441 (group 6), 405 (group 5), 364 (group 4), 317 (group 2),
      and 302 (group 3). Statistically significant differences were found between
      groups 1 vs 2, 1 vs 3, and 3 vs 7 (p < 0.05). CONCLUSION: The fracture resistance
      of endodontically treated premolars with MOD preparations was enhanced by the use
      of the sandwich technique. The samples restored with posts predominantly showed
      restorable fractures, while teeth restored without posts mostly displayed
      unrestorable failures.

PMID- 17432403
TI  - Are we ready? A large-scale disaster like a pandemic flu or terrorist attack
      could overwhelm the nation's healthcare providers.

PMID- 17432404
TI  - The young people's plague.

PMID- 17432406
TI  - Reason to be happy. Chronic depression may rob you of more than joy: the evidence
      is piling up that it can also steal your health.

PMID- 17432405
TI  - On life support.

PMID- 17432407
TI  - A dose of reality. An eagerly awaited bird flu vaccine comes up short.

PMID- 17432409
TI  - Schools of medicine.

PMID- 17432408
TI  - Blogging their way through academe.

PMID- 17432410
TI  - The green invasion.

PMID- 17432411
TI  - Pricing out Medicare.

PMID- 17432412
TI  - Violence interrupted.

PMID- 17432414
TI  - What dreams are made of.

PMID- 17432413
TI  - Birthing by appointment.

PMID- 17432415
TI  - Decision time.

PMID- 17432416
TI  - Going out on a limb.

PMID- 17432417
TI  - Calcium and common sense.

PMID- 17432418
TI  - Largest Grad Programs.

PMID- 17432419
TI  - Mix, match, and switch.

PMID- 17432420
TI  - Divining death's cause.

PMID- 17432421
TI  - Who says what's best?

PMID- 17432422
TI  - Some hope on stem cells.

PMID- 17432423
TI  - 17 and all burned out.

PMID- 17432424
TI  - Contraceptive confusion. There's a slew of new birth control methods to choose
      from. The best for you? It's the one you'll use correctly.

PMID- 17432425
TI  - An alarming link.

PMID- 17432426
TI  - Hearing the roar of cancer.

PMID- 17432427
TI  - No more excuses! There's no magic elixir for a long and healthy life, but
      exercise comes darned close. So get moving.

PMID- 17432428
TI  - Neither rain nor snow nor breast cancer.

PMID- 17432429
TI  - When your boss says jump. You may see a payoff in working out at work.

PMID- 17432430
TI  - We're born to walk.

PMID- 17432431
TI  - Breaking the silence: an HIV-related educational intervention for medical
      students in Zimbabwe.
AB  - PROBLEM: A culture of silence surrounding HIV is a major contributor to continued
      HIV transmission and poor care for people living with HIV/AIDS. AIM: To encourage
      medical leadership in addressing stigma and fear related to HIV at individual and
      community levels OBJECTIVE: To pilot a mini-course for final year medical
      students in Zimbabwe that demonstrates stigma-reduction knowledge and skills
      needed to communicate information about HIV to patients, to address ethical
      implications of testing versus not testing for HIV, to increase awareness of the
      medical and preventive benefits of knowing one's HIV status and showing people
      how to cope with the emotional burden of dealing with HIV everyday. DESIGN:
      Methods of proven effectiveness for training medical students in ethics and
      communication skills were used such as presentations by well respected role
      models and opinion leaders, role-playing, small group discussions, accompanied by
      materials indicating local resources, in three afternoon teaching sessions.
      SETTING: University of Zimbabwe College of Medicine. PARTICIPANTS: 60 medical
      students, six lecturers, two facilitators and a group of actors. MAIN OUTCOME
      MEASURES: Evaluation of the course by students showed appreciation of the course
      as measured on a scale of one to five for content and usefulness with requests
      for further inputs into the curriculum; model of mini-course that can be used by
      other medical schools in the southern Africa region and other areas of emerging
      HIV epidemics. CONCLUSIONS: A brief educational intervention can help medical
      students to cope with the extraordinary challenge of providing care in high HIV
      prevalence countries and may contribute towards better leadership in addressing
      HIV epidemics.

PMID- 17432433
TI  - A KAP study of the attitude and practice of traditional medicine in a
      contemporary Nigerian community.
AB  - OBJECTIVE: To study the knowledge, attitude and practice of traditional medicine
      among Nigerians in a contemporary selected community. DESIGN: Structured, fixed
      alternative, self-administered questionnaires constituted the research
      instrument, which was randomly distributed among the sampled population of 320
      respondents. SETTING: Agege Local Government Area located in Lagos State, Nigeria
      and consisting of diverse tribes, different social classes, religious beliefs and
      levels of literacy. Subjects above the age of 12 years were selected for the
      study. RESULTS: Out of the 320 copies of the questionnaire distributed, 300 were
      returned. It was observed that 134 (44.7%) had a knowledge of traditional
      medicine and what it entails. A total of 101 (33.7%) believed that every ailment
      has spiritual implications and that drugs alone are not adequate for therapy.
      Furthermore, the majority of the subjects considered traditional medicine
      unreliable when used alone. They would, therefore, combine it with orthodox drugs
      for better efficacy. However, only 8.3% advocated the replacement of western
      medicine by traditional medicine. There was an association between age,
      educational background and knowledge of traditional medicine (p < 0.01).
      CONCLUSION: The secrecy of practitioners has hampered access to the therapeutic
      benefit of the system of medicine to the general population. However, traditional
      medicine is still employed since it is a part of African cultures, and because of
      the unavailability of western medicine. Such employment of traditional medicine
      has resulted in misuse and consequently, adverse drug reactions.

PMID- 17432432
TI  - Preterm delivery risk in relation to maternal HIV infection, history of malaria
      and other infections among urban Zimbabwean women.
AB  - OBJECTIVE: To examine preterm delivery risk in relation to maternal HIV
      infection, malaria history, and other infections among Zimbabwean women. DESIGN:
      Hospital based, cross sectional study. SETTING: Harare Maternity Hospital,
      Harare, Zimbabwe. SUBJECTS: A convenient sample of 500 pregnant women. MAIN
      OUTCOME MEASURE: Preterm delivery. THE STUDY FACTORS: Maternal socio-demographic
      information, and infectious disease history (during the year before pregnancy).
      METHOD: Between July 1998 and March 1999 data were collected for a cross
      sectional study of pregnant women who delivered at the Harare Maternal Hospital.
      The association of maternal HIV infection, history of malaria, and other
      infections with preterm delivery were determined using multivariate analysis.
      RESULTS: Overall, 497 women were studied, 444 (89.3%) delivered at term and 53
      women (10.7%) delivered preterm. Women who delivered preterm were less likely to
      be HIV seropositive compared with others (odds ratio [OR] = 0.75. 95% confidence
      interval (CI): 0.38 to 21.48). Preterm delivery was associated with having
      tuberculosis infections in the year prior to the pregnancy (OR = 10.15, 95% CI:
      1.15 to 89.87). Other infections associated with preterm delivery were malaria
      (OR = 2.39, 95% CI: 1.07 to 5.31), chest infections (OR = 2.63, 95% CI: 0.76 to
      9.17), and Herpes (shingles) infection (OR = 2.58, 95% CI: 0.56 to 11.85).
      Overall, a positive history of any of the non-sexually transmitted infections (in
      aggregate) was associated with a 3.20 fold increase risk for preterm delivery (OR
      = 3.20. 95% CI: 1.59 to 6.43). Women with a history of infection and who did not
      use iron supplements during pregnancy, compared with women without such an
      history and who used iron supplements, experienced the highest risk for preterm
      delivery (OR = 8.34, 95% CI: 3.30 to 21.07). CONCLUSION: Maternal non-STD
      infections, (i.e., tuberculosis, malaria, and chest infections) occurring in the
      year prior to pregnancy were associated with an increased risk of preterm
      delivery. The association of non-sexually transmitted infections and preterm
      delivery was particularly strong among women who did not use iron supplements
      during pregnancy.

PMID- 17432434
TI  - Geographical distribution of pulmonary tuberculosis cases notified during one
      year in Gweru, Zimbabwe.

PMID- 17432435
TI  - Is there room for the soul?

PMID- 17432436
TI  - Conquering cravings.

PMID- 17432437
TI  - Closing in on a cure.

PMID- 17432438
TI  - Progress towards poliomyelitis eradication in Afghanistan and Pakistan, January
      2006 to February 2007.

PMID- 17432439
TI  - New technologies for tuberculosis control: the Stop TB Partnership's Task Force
      on Retooling.

PMID- 17432440
TI  - Bibliography. Current world literature. Seizure disorders.

PMID- 17432442
TI  - [Procedures in Lucerne in the cases of magic and witchcraft until the middle of
      the 16th century].

PMID- 17432443
TI  - Aliskerin, an oral renin inhibitor, in combination with a thiazide diuretic, ace
      inhibitor, or angiotensin receptor antagonist reduces 24-hour blood pressure and
      suppresses plasma renin activity.

PMID- 17432444
TI  - [The repression of witchcraft in the region around Geneva before the
      Reformation].

PMID- 17432445
TI  - ["Sexual misdemeanors," "anticipation," and forced marriages in Geneva in the
      18th century: the point of view of the Consistory, fathers, and judges].

PMID- 17432446
TI  - Blood pressure control rates in Spain are further improved using daytime
      ambulatory measurements than when using conventional office based measurement.

PMID- 17432447
TI  - [Witch-hunts in the Pays de Vaud (1430-1530): a summary of research].

PMID- 17432448
TI  - [Unhappy marriage: failed marriages in confessions of the late 18th century].

PMID- 17432449
TI  - [Gender groupings in the social gatherings of the Enlightenment].

PMID- 17432450
TI  - [Times of purity, places of luxury].

PMID- 17432451
TI  - [Fatherly discourses: sons and daughters in the correspondence of Albrecht von
      Haller].

PMID- 17432452
TI  - Management of open fractures and subsequent complications.

PMID- 17432453
TI  - [Witchcraft trials in Neuchatel in the 15th century: some remarks].

PMID- 17432454
TI  - Approved: process for missing CLIA certificates for waived testing.

PMID- 17432455
TI  - Top standards compliance issues for 2006.

PMID- 17432457
TI  - Revision: Standard LD.7 for health care staffing services.

PMID- 17432456
TI  - Approved: 2007 fixed components for random unannounced surveys.

PMID- 17432458
TI  - [Diagnosis and treatment of eosinophilic otitis media and paranasal sinusitis].

PMID- 17432459
TI  - [6th Congress of Physiatrists in Serbia and Monte Negro with international
      participation held at the Zvezda Congressional Center in Vrnjacka Banja. 1-4
      November 2006].

PMID- 17432460
TI  - Spring quiz. Resorbed mandible.

PMID- 17432461
TI  - Is your facility's emergency response strategy updated?

PMID- 17432462
TI  - How does your salary measure up?

PMID- 17432463
TI  - What can civilian biomeds learn from the military?

PMID- 17432464
TI  - Are clinical alarms still an issue?

PMID- 17432465
TI  - Understanding the pneumatic flow of oxygen.

PMID- 17432466
TI  - Using daily rounds to drive quality assurance.

PMID- 17432467
TI  - Smart pump technology.

PMID- 17432468
TI  - Imaging customer surveys point the way to new call center.

PMID- 17432469
TI  - In search of higher education.

PMID- 17432470
TI  - IT security basics: what you need to know.
AB  - We've touched on many aspects of IT security in this overview. The most important
      thing to remember is that security starts with the user. Keeping your password
      safe and difficult to decipher is a good start. Awareness of social engineering
      techniques is another easy way to apply security measure. This means not only
      being very skeptical of anyone asking for your logon credentials but also for
      things such as if you know the password to the patient monitoring system or any
      other place where patient data is stored. There are many references available at
      your local bookstore or on the web about social engineering and all the security
      topics discussed in this installment of IT World. Our recommended resources are
      listed in the bibliography sidebar.

PMID- 17432471
TI  - An engineer's role in preparing for FDA inspections.

PMID- 17432472
TI  - The impact of usability on patient safety.

PMID- 17432473
TI  - Interpreting and understanding microbial data in validation of ethylene oxide
      sterilization processes.
AB  - Ethylene oxide (EtO) sterilization validation programs are based on historical
      data, industry experience, and theoretical knowledge. When designing a specific
      program, the knowledge and experience of the individuals responsible often
      determines how accurately these data, experiences, and theories are applied. The
      assumptions and premises that form the foundation for the validation program are
      critical to the ultimate safety ofproducts distributed to the marketplace.
      Demonstrating appropriate microbial lethality is the ultimate purpose of
      sterilization validation. When using EtO processes, this is usually dependent on
      the proper use of biological indicators (Bls) in conjunction with the specific
      product, load, and cycle to be validated. The authors discuss the use of Bls,
      determination of microbial lethality, process controls, and variables related to
      these subjects in order to assist validation teams in designing successful
      validation programs, and/or problem solving when unexpected results are obtained.

PMID- 17432474
TI  - Demystifying standards: the six-step life cycle.

PMID- 17432475
TI  - State discretion and medicaid program variation in long-term care: when is
      enough, enough?
AB  - Although federal statutes and regulations establish the broad parameters within
      which state Medicaid programs operate, the federal government grants states
      substantial discretion over Medicaid and Medicaid-funded long-term care. An
      appreciation of resulting cross-state variation in Medicaid program
      characteristics, however, has been lacking in the ongoing debate over whether the
      federal government should further devolve responsibility for caring for the poor
      and disabled elderly to the states. To better inform this discussion, therefore,
      this article documents considerable variation, not only in terms of Medicaid
      program spending and recipients, but also in terms of strategies chosen to reform
      long-term care services and financing. Since there is little doubt that states
      take full advantage of current levels of discretion, advocates of devolution may
      want to reassess their views to consider whether existing variation has resulted
      in inequities addressable only through more, not less, federal involvement.

PMID- 17432476
TI  - Devolution of employment and training policy: the case of older workers.
AB  - The case for the devolution of employment and training programs has traditionally
      been based on the supply side argument that state and local governments are in
      the best position to assess the training needs of their disadvantaged workers. We
      provide a different perspective by focusing on the demand side of the labor
      market and the link between aiding older workers and fostering economic growth.
      We illustrate the importance of this focus by examining the labor market in
      Massachusetts, where the full employment economy of the late 1990s resulted in
      serious labor supply bottlenecks. Older workers, whose ranks are growing rapidly,
      provide the largest known labor reserve for meeting these labor supply deficits
      in the next decade. Tapping this reserve, however, means improving skills,
      deferring retirement, bringing older persons back into the labor market, and
      increasing full-time employment. Massachusetts already has the policy tools
      needed to train older workers to fill emerging job needs, but these policies will
      need to be substantially upgraded and reoriented. Too little funding, an emphasis
      on short-term programs, lack of coordination among programs, weak linkages to the
      private sector, and the limited flexibility of human resources practices in both
      the private and public sectors have left both government programs and employers
      ill-prepared to utilize fully the older worker labor reserve.

PMID- 17432477
TI  - Volunteerism and social capital in policy implementation: evidence from the Long
      Term Care Ombudsman Program.
AB  - We assess the link between a program's volunteer support and state social capital
      in the case of the joint implementation of the federal Long-Term Care (LTC)
      Ombudsman Program by state and federal authorities. This program, which is
      designed to prevent elder abuse and ensure quality care in long-term facilities,
      is implemented at the state and local levels and relies heavily on volunteer
      staff. First, we find that volunteerism is vital to the efficacy of the program's
      monitoring and investigative functions. Second, we find that volunteerism in this
      program is tied to broader level conditions of a state's social capital. Last, we
      discuss the implications of our findings for volunteer-based programs devolved to
      the states.

PMID- 17432478
TI  - Partnership insurance: an innovation to meet long-term care financing needs in an
      era of federal minimalism.
AB  - In the case of long-term care financing, federal minimalism is not new news. Long
      term care has long played a weak "third fiddle" to national health reform
      concerns about the uninsured and catastrophic expenditures on prescription drugs.
      The states have been left to struggle with the issue of long-term financing as
      part of their responsibilities in funding and administering the means-tested
      Medicaid program. Recently, the environment has become even more challenging.
      Much of what is on the national agenda for health and welfare reform has been
      delegated to the states. This "devolution" of responsibilities has created many
      competing priorities for both the attention and resources of states. This context
      of evolving federal minimalism calls for creative solutions that balance
      competing points of view. In this article, we provide some background and
      insights from one such effort: a collaboration between state governments and
      private insurers to put into operation an insurance-based approach to long-term
      care financing that uses Medicaid as an incentive to encourage potential
      purchasers.

PMID- 17432479
TI  - Implementation issues for consumer-directed programs: comparing views of policy
      experts, consumers, and representatives.
AB  - An increasing number of aging community providers and consumers support consumer
      direction (CD) in long-term care services. In regard to devolution, consumer
      direction goes beyond the usual approach of shifting responsibilities from the
      federal government to state governments to bring programs "closer to the people."
      Consumer-direction goes even further by placing resources directly in the hands
      of consumers. Yet, many questions remain unanswered regarding how to implement CD
      personal assistance services in general, and especially for older persons. This
      article describes the importance of examining views from multiple key
      stakeholders involved in implementing CD programs. We report on three background
      studies that have informed the Cash and Counseling Demonstration and Evaluation
      (CCDE) design and implementation-policy expert interviews as well as surveys and
      focus groups with consumers and representatives. As a fourth data source, we drew
      upon experiences in designing the CCDE and initial results from the first year of
      implementation. Each of the three studies on its own provided essential
      information for planning the CCDE. However, when we examined the studies
      together, and added CCDE design and implementation experiences, views expressed
      by the different stakeholders formed a type of multi-perspective "dialogue" that
      expanded our knowledge about implementing CD services. We hope this increased
      knowledge will help expand the availability of such services for consumers of any
      age who want to direct their own care.

PMID- 17432480
TI  - Weighing the success of a national Alzheimer's disease service demonstration.
AB  - As the need for long-term care services within the United States has grown
      dramatically, Congress has consistently deflected the primary responsibility for
      such care to state governments, local organizations, and, ultimately, the family.
      This paper examines the impact of the Alzheimer's Disease Demonstration Grants to
      States (ADDGS) program, a small federally funded initiative within the context of
      this trend. Although the demonstration can be deemed a huge success relative to
      the goals of creating new services for an underserved target population,
      questions are raised about the merits of the program relative to the exploding
      need for an effective network of long-term care services.

PMID- 17432481
TI  - Strengthening senior tax credit programs in Massachusetts.
AB  - In the last decade, property taxes have increased, creating a financial burden on
      senior homeowners. In Massachusetts, senior property tax credit programs have
      arisen to address this problem, as well as to provide cost-effective volunteer
      assistance for municipal departments, offer seniors meaningful work that
      otherwise would not have been attempted, and foster involvement in municipal
      government among seniors. The success of the programs in retaining senior
      homeowners in the community remains to be evaluated. Program specifics are
      detailed, policy options are considered, and recommendations are made to
      strengthen existing programs and assist replication.

PMID- 17432482
TI  - Assessing state efforts to meet baby boomers' long-term care needs: a case study
      in compensatory federalism.
AB  - The role of the state government and the character of federal-state relations in
      social policy have evolved considerably. Frank Thompson uses the phrase
      compensatory federalism to describe increased activity by state governments to
      make up for a diminished federal role. For compensatory federalism to work, it is
      essential for states to take leadership roles in key policy areas. Few studies
      examine whether states have risen to the challenge of compensatory federalism in
      social policy. This paper examines an emerging issue of great significance in
      social policy-challenges involved in meeting future long-term care needs for the
      baby boomer generation. The paper provides an in-depth case study of attempts by
      Maryland to meet the challenges of financing long-term care needs for the baby
      boomer generation. The detailed description of the agenda-setting and problem
      structuring process in Maryland is followed by an analysis that uses three
      different frameworks to assess the policy development processes. These models are
      rooted in a bureaucratic politics perspective, an agenda-setting perspective and
      an interest group politics perspective. The paper concludes with a discussion of
      the limitations and possibilities of state leadership in the social policy
      sphere.

PMID- 17432483
TI  - Naturally Occurring Retirement Community-Supportive Service Program: an example
      of devolution.
AB  - Devolution is defined as the transfer of power or authority from a central
      government to a local government. This article addresses federal policies on
      housing for the elderly and the devolution of funding for federal senior housing
      and describes two aspects of devolution of federal housing policy for the
      elderly. One, it points out the decreasing interest in senior housing by federal
      authorities as indicated by the decreased amount of funds allocated for this
      purpose. Two, it emphasizes the need for supportive, assistive services for
      residents of senior housing and how federal funds have not addressed this need
      adequately or sufficiently. As a consequence, there have emerged Naturally
      Occurring Retirement Communities (NORCs) in New York State, a housing arrangement
      that provides supportive and health services to all eligible residents. The
      article concludes with a discussion of policy implications and the need for
      additional research before replicating this model.

PMID- 17432484
TI  - Information technology issues in an era of greater state responsibilities: policy
      concerns for seniors.
AB  - Five areas of state information technology policy are of special concern to
      seniors and senior service providers: obtaining access; closing the digital
      divide; developing information management systems; creating portals; and
      maintaining privacy. Increasing their activities in each of these areas, states
      continue to vary considerably in their responsiveness to meeting the challenge of
      including older adults, especially those living in rural areas, with the benefits
      of information technology.

PMID- 17432485
TI  - A consumer cooperative association specializing in services for the elderly.
AB  - Over the past 10 years, a Japanese cooperative association named Fukushi Club
      Seikyo (FCS) has developed a unique, non-profit business specializing in services
      for the elderly. It aims to promote a reciprocal support system among
      neighborhood community members. FCS has successively organized its active
      members, mainly homemakers, into workers' collectives and successfully provided
      various life support services at a very small charge. Their human-touch service
      appears in sharp contrast to bureaucratic public services and profit-making
      private services. The civil initiative presented by FCS suggests a potential for
      a community-based social service system that may guarantee quality services
      without raising taxes and premiums for social insurance.

PMID- 17432486
TI  - Kaiser Permanente's manifesto 2005 demonstration: the promises and limits of
      devolution.
AB  - In 1996, the eight-million member Kaiser Permanente HMO adopted a vision
      statement that said by 2005 it would expand its services to include home- and
      community-based services for its members with disabilities. It funded a 3-year,
      32-site demonstration that showed that it was feasible to link HMO services with
      existing home-and community-based (HCB) services and that members appreciated the
      improved coordination and access. This private-sector project showed that
      devolution can produce innovative and feasible models of care, but it also showed
      that without federal financial and regulatory support, such models are unlikely
      to take hold if they are focused on "unprofitable" populations, for example,
      those who are chronically ill, poor, and/or disabled.

PMID- 17432487
TI  - Age concerns: innovation through care management.
AB  - Age Concerns is a proprietary care management firm serving the elderly.
      Established in 1982, the firm has prospered by employing an integrated model of
      care whereby the caregivers are employees of Age Concerns. In addition, the
      firm's ability to keep the elderly at home, out of institutional care, has
      resonated with consumers. Various features of Age Concerns--organizational
      format, characteristics of consumers, and economic considerations-are described.
      In 2001, Age Concerns was acquired by the Senior Care Action Network, a social
      health maintenance organization. In an increasingly commercial environment in
      which the elderly are a burgeoning market, Age Concerns may be a prototype of
      future elder-care service delivery.

PMID- 17432488
TI  - Characteristics of adults with serious psychological distress as measured by the
      K6 scale: United States, 2001-04.
AB  - OBJECTIVE: This report estimates the prevalence of serious psychological distress
      (SPD) in the noninstitutionalized adult population of the United States, as
      measured by the K6 scale of nonspecific psychological distress, and describes the
      characteristics of adults with and without SPD. These findings are compared with
      results from previous studies of the characteristics of adults with serious
      mental illnesses that cause significant disability, such as severe major
      depression, bipolar disorder, and schizophrenia. METHODS: The estimates in this
      report were derived from the Family Core and Sample Adult components of the 2001
      04 National Health Interview Survey, conducted by the Centers for Disease Control
      and Prevention's National Center for Health Statistics (NCHS). Estimates were
      calculated using the SUDAAN statistical package to account for the complex survey
      design. RESULTS: The prevalence of SPD was higher among adults 45-64 years old
      than younger adults 18-44 years or older adults 65 years and over. Adults with
      SPD were more likely to be female, have less than a high school diploma, and live
      in poverty, and less likely to be married than adults without SPD. Moreover,
      those with SPD were more likely to be obese and to be current smokers. They have
      a higher prevalence of ever being diagnosed with heart disease, diabetes,
      arthritis, and stroke than persons without SPD. Adults with SPD were more likely
      to report needing help with activities of daily living (ADLs) and instrumental
      activities of daily living (IADLs). They also used more medical care services
      such as doctor visits and visits to mental health professionals than adults
      without SPD. CONCLUSIONS: The associations between SPD and sociodemographic
      characteristics, health status, and health care utilization are similar to the
      relationships found between serious mental illnesses (for example, major
      depression or schizophrenia) and these same variables. Persons with SPD
      demonstrate disadvantage in both socioeconomic status and health outcomes.

PMID- 17432489
TI  - Poetic closure, psychoanalytic termination, and death.
AB  - Our pull to grasp narrative structures--including beginnings and especially
      endings--applies not only to the intentional craft of fictions, but to life as
      lived, as it is in psychoanalytic termination. Remarkable parallels, for
      instance, exist between thematic closure in poems and the conscious and
      unconscious signals of closure that develop in pretermination and accelerate in
      termination proper. A case illustrates this point: the slow crescendo of cues
      begins months before the first "pretermination dream." It is the patient's
      emerging awareness of greater health and freer functioning that likely gives rise
      to these phenomena, yet this awareness is often warded off because of the grave
      task of ending that it implies. Literature and psychoanalysis share concerns with
      how an ending is borne. Fictive closure and apocalyptic narratives allude to or
      imply finality (i.e., death), and lesser "endings" in daily life may not escape
      the specter of that linkage. But Kermode asserts that "ending" confers
      significance on an entire narrative and may thereby console us. Coltart links the
      realities of mortality and psychoanalytic termination, yet falls short of
      consolation. Clues to the role of beginnings (in final matters) and how they may
      help emerge from considering Basho's last days and poems. Nonetheless, the power
      of narrative has its limits in helping us bear the burden of a real ending, as of
      an analysis. Joining present to future, as through normal hope, or joining
      present to past through normal nostalgia, works toward a "bearing of the burden"-
      but only within the context of health achieved through the analysis.

PMID- 17432490
TI  - Ephemera--unfinished thoughts on psychoanalysis, poetry, endings, and death:
      commentary on Caston.

PMID- 17432491
TI  - A working poet comments on Caston's "poetic closure, psychoanalytic termination,
      and death".

PMID- 17432492
TI  - To coerce and be coerced.
AB  - Coercion is a way of forcibly influencing others. While one's core conflicts may
      contribute to an experience of being coerced in any interaction, specific
      situations or circumstances commonly encountered in clinical practice set the
      stage for analyst or patient to feel forced or manipulated. The interaction that
      develops in these instances is conceptualized as a coercive enactment. Conditions
      that increase the susceptibility to coercing and being coerced may develop at any
      stage in the psychoanalytic process. Supervision and conversion from
      psychotherapy to psychoanalysis are examined as situations that predispose to
      coercion. Silences and other difficulties in maintaining the analytic frame, as
      well as crises in the life of the analyst, may also lead to coercive enactments.
      Pertinent literature is reviewed and illustrative clinical cases are presented.

PMID- 17432493
TI  - Nothing but the truth: self-disclosure, self-revelation, and the persona of the
      analyst.
AB  - The question of the analyst's self-disclosure and self-revelation inhabits every
      moment of every psychoanalytic treatment. All self-disclosures and revelations,
      however, are not equivalent, and differentiating among them allows us to define a
      construct that can be called the analytic persona. Analysts already rely on an
      unarticulated concept of an analytic persona that guides them, for instance, as
      they decide what constitutes appropriate boundaries. Clinical examples illustrate
      how self-disclosures and revelations from within and without the analytic persona
      feel different, for both patient and analyst. The analyst plays a specific role
      for each patient and is both purposefully and unconsciously different in this
      context than in other settings. To a great degree, the self is a relational
      phenomenon. Our ethics call for us to tell nothing but the truth and
      simultaneously for us not to tell the whole truth. The unarticulated working
      concept of an analytic persona that many analysts have refers to the self we step
      out of at the close of each session and the self we step into as the patient
      enters the room. Attitudes toward self-disclosure and self-revelation can be
      considered reflections of how we conceptualize this persona.

PMID- 17432494
TI  - The patient's experience of validation in psychoanalytic treatment.
AB  - The importance of the patient's experience of validation is not a new one in
      psychoanalytic thinking, and can be traced throughout the literature. However,
      its role as an essential aspect of the psychoanalytic process, particularly in
      working with intrapsychic conflict, has traditionally been underappreciated. It
      is argued that validating interventions have an important role in psychoanalytic
      treatment, and that they often serve to open up, rather than foreclose, the
      analysis of transference. Marsha Linehan's conceptualization of the role of
      validation in Dialectical Behavioral Therapy provides a unifying framework for a
      more extensive psychoanalytic consideration of validation. After a review of the
      psychoanalytic literature, a number of conceptual issues are discussed that have
      complicated thinking about validation from a psychoanalytic perspective. Two
      clinical examples are presented, one from the author's psychoanalytic practice
      and one from his own analysis. Both illustrate how active validation by the
      analyst can play an essential facilitating role in the psychoanalytic process.

PMID- 17432495
TI  - Intentional attunement: mirror neurons and the neural underpinnings of
      interpersonal relations.
AB  - The neural circuits activated in a person carrying out actions, expressing
      emotions, and experiencing sensations are activated also, automatically via a
      mirror neuron system, in the observer of those actions, emotions, and sensations.
      It is proposed that this finding of shared activation suggests a functional
      mechanism of "embodied simulation" that consists of the automatic, unconscious,
      and noninferential simulation in the observer of actions, emotions, and
      sensations carried out and experienced by the observed. It is proposed also that
      the shared neural activation pattern and the accompanying embodied simulation
      constitute a fundamental biological basis for understanding another's mind. The
      implications of this perspective for psychoanalysis are discussed, particularly
      regarding unconscious communication, projective identification, attunement,
      empathy, autism, therapeutic action, and transference-countertransference
      interactions.

PMID- 17432496
TI  - A contemporary integration of modern and postmodern trends in psychoanalysis.
AB  - Postmodernism has appeared on the psychoanalytic horizon and with it brought
      change and some confusion. Although many link or even conflate it with relational
      and intersubjectivity theory, those views are as subject to a postmodernist
      critique as other analytic orientations. Postmodernism can also be seen as
      usefully informing the concepts of psychoanalytic narrative and psychoanalytic
      space. It should not be viewed as an organized theory or movement that would
      entirely replace modernist ideas in psychoanalysis. Indeed, valid critiques of
      both modern and postmodern psychoanalytic positions have been advanced. In this
      climate the need for a viable integration remains urgent. Bruno Latour's
      development of the concept of hybrid structure as a way of dealing with the same
      kind of impasse in the field of science studies is presented, along with its
      applicability to the dilemma faced by psychoanalysis.

PMID- 17432497
TI  - Unconscious fantasy: a once and future concept.
AB  - The concept of unconscious fantasy should be retained as fundamental to any
      psychoanalytic approach. The concept is reexamined in the face of two challenges:
      today's theoretical pluralism and the recent integration of findings from
      academic research. The first section reviews post-Freudian theoretical
      contributions to Freud's original concept, concluding that in its evolved form it
      is flexible enough to serve multiple perspectives. The second section examines
      four features identified with primary process thinking, demonstrating that a
      model of early mentation based on adult dream work cannot be supported by
      research on early development. However, the contemporary concept of unconscious
      fantasy is compatible with research findings from child development studies and
      cognitive neuroscience, permitting psychoanalysts to enter dialogue with those
      fields. Our contribution is not the posit of a new form of thinking (primary
      process) but an understanding of how general cognitive processes are enlisted for
      motivated purposes.

PMID- 17432498
TI  - Psychotherapy and psychoanalysis: fifty years later.

PMID- 17432499
TI  - Psychoanalytic research using longitudinal studies: an inquiry on the
      developmental impact of early maternal projections.

PMID- 17432500
TI  - Maternal and fetal representations, dimensions of personality, and prenatal
      attachment in women hospitalized with high-risk pregnancy.

PMID- 17432501
TI  - Changes in adolescent attachment relationships as a response to wilderness
      treatment.

PMID- 17432502
TI  - It's hard to say: the challenge of connecting emotions and language for first
      time mothers.

PMID- 17432503
TI  - Do mothers of secure infants speak differently than mothers of avoidant infants
      in natural conversations? An interpersonal exploration of language differences.

PMID- 17432504
TI  - Exploration of women's body experiences surrounding first childbirth.

PMID- 17432505
TI  - Facilitating effective coping in children following disasters: a
      psychoanalytically informed guided narrative intervention.

PMID- 17432506
TI  - Parental influences on social anxiety: the sources of perfectionism.

PMID- 17432507
TI  - The creation of a coding scheme assessing curiosity expression in adolescent
      interviews: preliminary findings.

PMID- 17432508
TI  - Differential selectivity of patients assigned to long-term psychoanalytic
      treatment.

PMID- 17432509
TI  - Psychometric properties of a Chinese version of the Psychological Mindedness
      Scale.

PMID- 17432510
TI  - Psychoanalytic analysis of texts by Adam Smith (1723-1790).

PMID- 17432511
TI  - Reliability of a multidimensional measure for scoring reflective function.

PMID- 17432512
TI  - Helplessness in depression: the unbearable riddle of the other.

PMID- 17432513
TI  - Development of the Dyadic Reflective Functioning Questionnaire (DRFQ).

PMID- 17432514
TI  - [Familial short QT syndrome].
AB  - Short QT syndrome is a newly described cardiologic entity which associates a
      short OT interval (QT and QTc < or = 300 ms) on the surface ECG to a high risk of
      syncope or sudden death due to malignant ventricular arrhythmia. This extremely
      rare syndrome affects mainly young adults or infants and has a wide clinical
      expression. It is frequently associated with atrial fibrillation. Mutations in 3
      different genes KCNQ1, KCNH2, and KCNJ2, all encoding cardiac ionic potassium
      channels have been identified in affected patients. The clinical spectrum is very
      wide ranging from asymptomatic carriers to syncope or sudden death. It is an
      autosomal dominant transmission. Expression studies have shown a gain of function
      and a shortening of the action potential duration thus explaining the short OT
      interval. At electrophysiologic study, atrial and ventricular refractory periods
      are short, and ventricular fibrillation inducible in the majority of patients. As
      of today, automatic implantable defibrillator is the only effective treatment for
      the prevention of sudden death in the short QT syndrome.

PMID- 17432515
TI  - [Dermatomyositis and colon cancer].

PMID- 17432516
TI  - [Parasitic diseases. Persistent and cosmopolitan].

PMID- 17432517
TI  - [World epidemiology of parasitic diseases].
AB  - Parasitic diseases are cosmopolitan and may affect all the world population. They
      kill several million people every year. The migrations and tourism make that even
      tropical diseases can be frequently met outside their geographical distribution
      area. Except the arthropod-borne infections, the great majority of these diseases
      are in relation with the faecal contamination of soil, the general level of
      hygiene and the food practices. Malaria remains the first world parasitic disease
      in term of mortality. The strong fall of the amoebic endemicity is due only to
      the improvement of the methods of molecular diagnosis. The socio-political and
      climatic upheavals may result in a creeping extension of the geographical limits
      of many parasites.

PMID- 17432518
TI  - [Parasitic diseases and pregnancy].
AB  - In tropical areas, parasitic diseases are very frequent during pregnancy. Malaria
      is the most frequent, with different complications in pregnant women (anaemia,
      cerebral malaria, abortion) and in the fetus (low birthweight, congenital
      malaria), mostly after first pregnancies. Diagnosis must be confirmed rapidly and
      the treatment is effective with most of antimalarial drugs. Prophylaxis is
      possible by intermittent sulfadoxine-pyrimethamine treatment. Hookworms
      infestation increases the anemia. Schistosomiasis can be liable to sterility or
      dystocia. Congenital transmission of visceral leishmaniasis is exceptional.
      Digestive parasitosis give few repercussion on pregnancy and their treatment is
      useful only if clinical troubles are important.

PMID- 17432519
TI  - [Bilharziasis or schistosomiasis].
AB  - Schistosomiasis has been known and described since Antiquity. However, the
      pathogens were not clearly identified until the 19th century for Schistosoma
      haematobium, the 20th century for S. mansoni, S. japonicum, then S. intercalatum
      and S. mekongi. The lastest identified species is a hybrid between S. haematobium
      and S. intercalatum (Gabon, Cameroon). Given the frequent population exchanges
      with Southeastern Asia, schistosomiases caused by S. japonicum and S. mekongi are
      given more and more importance. Major migrations, dam and irrigation schemes and
      the various control programs modify the prevalence of the different types of
      schistosoma. In the foci where different species coexist, phenomena of
      competition and hybridization have been reported. For certain species, the
      definitive animal hosts have not all been identified, which constitutes an
      additional obstacle in disease control. The evocative clinical signs are not
      observed until the acme. Before this stage, the clinical diagnosis is difficult
      to establish and the signs are misleading. In the invasive phase, the laboratory
      diagnosis is made based on serology, showing hypereosinophilia, while at acme,
      the diagnosis is confirmed by the finding of eggs with a spine. Currently, only
      praziquantel is used in clinical practice, both for individual treatments and
      mass treatment campaigns, despite the development of a resistance to this
      molecule in well-defined foci. Other therapeutic protocols based on artemether
      are being used. Control programs aiming at decreasing the incidence of
      schistosomiasis are hampered by the implementation of irrigation schemes
      favorable to the development of mollusks and to disease transmission.

PMID- 17432520
TI  - [Filariasis].
AB  - Filariasis are vector-transmitted parasitoses, exclusively tropical, except for
      dirofilariosis. Their impact differs according to the type of filaria and the
      induced immune response. The diagnosis is made based on the presence of
      dermatological or lymphatic manifestations, acute or chronic, associated with
      usually extended stays in an endemic country. It can also be established
      following a laboratory examination revealing hypereosinophilia or correspond to
      the incidental finding of microfilariae (blood or skin). The visualization of the
      embryonic and/or adult parasite confirms the infection. For pathogenic filariasis
      with microfilaremiae, paradoxically, clinically positive subjects are often
      amicrofilaremic. In this case, the presence of antibodies and/or specific serum
      antigens confirms the diagnosis. On the contrary, asymptomatic
      microfilariaecarriers are common but there is no guarantee that they will remain
      asymptomatic. The etiological treatment of choice is based on a combination of
      ivermectin and albendazole. However, diethylcarbamazine, which was formerly used,
      is still indicated. Dracunculiasis has been almost eradicated and the elimination
      of lymphatic filariasis and onchocerciasis as public health problems can be
      contemplated in the medium term.

PMID- 17432521
TI  - [Parasitic infection in immunocompromised patients].
AB  - Several parasites are responsible for life threatening infections in
      immunocompromised patients. They occur in patients with a profound
      immunodeficiency affecting the T-cell mediated immunity. In AIDS patients,
      opportunistic infections are highly prevalent in those with CD4 lymphocyte counts
      < 200/mm3. Most of these parasites are intracellular protozoa. Severe parasitic
      infections in immunocompromised hosts either results from the reactivation of a
      previously acquired infection, such as toxoplasmosis, or from a primary acquired
      infection which manifests more severely because of the immune defect: this is the
      case for intestinal protozoa, such as Cryptosporidium, microsporidia, Cyclospora
      and Isospora belli which can be the cause of severe chronic diarrhea and for
      visceral leishmaniasis. Strongyloides stercoralis is the only helminth
      responsible for disseminated infection in immunocompromised patients. For each
      parasite, recommendations for preventing infection or specific chemoprophylaxis
      are efficient for prevention of opportunistic infections. Immune reconstitution
      also proved very efficient to reduce their incidence during VIH infection.

PMID- 17432522
TI  - [New drugs against parasitic diseases].
AB  - The gap in the antiparasitic armamentarium is still not filled in 2006 and few
      original and useful drugs were marketed in the last decade. Against malaria,
      artemether combined with lumefantrine is adopted as first line therapy in a
      majority of endemic countries but still not available in France and several
      european countries. As its tolerance and efficacy are satisfactory, atovaquone
      proguanil, is taking a major place for prevention and treatment in travellers.
      Liposomal amphothericin B and miltefosine extended the treatment of visceral
      leishmaniasis. Nitazoxanide and triclabendazole may be usefull in
      cryptosoridiosis or giardiasis and fasciolasis, respectively.

PMID- 17432524
TI  - [Patient sheet: various hygiene and prevention steps for travelers].

PMID- 17432523
TI  - [Antiparasitic vaccines: where are we now?].
AB  - In more than one way, the development of antiparasitic vaccines is challenging,
      but major efforts have been made. A large number of clinical trials have been
      carried out and a few antigens have been tested in the endemic zone, especially
      against malaria. So far, no vaccine candidate has shown a sufficient and long
      lasting effectiveness that would be useful for public health. However, the trials
      have shown without ambiguity that a certain level of clinical immunity against
      paludism, schistosomiasis or leishmaniasis could be induced by vaccination, in
      the experimental setting or in the field.

PMID- 17432525
TI  - [Questions about funding: medical education].

PMID- 17432526
TI  - [Renal tumours].

PMID- 17432527
TI  - [Fracture of the lower end of the radius in adults].

PMID- 17432528
TI  - [Acute agitation and delirium].

PMID- 17432529
TI  - [Prevention of tetanus].

PMID- 17432530
TI  - [Follow-up of patients with artificial cardiac valves and protheses].

PMID- 17432531
TI  - [The water cure in France at the XIXth century: between scientific orthodoxy and
      naturist alternative].

PMID- 17432532
TI  - [Posterior ceramic bonded partial restorations].
AB  - Posterior ceramic bonded partial restorations are conservative and esthetic
      approaches for compromised teeth. Overlays constitute a less invasive alternative
      for tooth tissues than crown preparations. With inlays and onlays they are also
      indicated in case of full arch or quadrant rehabilitations including several
      teeth. This article screens indications and realization of this type of
      restorations.

PMID- 17432534
TI  - [Bonding-cementation of all-ceramic restorations].
AB  - The objective of this article is to synthesize the current scientific data
      relating to the bonding of ceramic restorations in order to present a reliable
      and reproductive clinical method for the general practitioner. The different
      ceramic treatments are explained with a distinction between those which can be
      etched and the others. A precise check list is suggested for the conditioning of
      dental tissues and ceramic surfaces.

PMID- 17432533
TI  - [Ceramic posts].
AB  - As a result of ceramics and all-ceram technologies development esthetic inlay
      core and abutments flooded the market. Their tooth-colored appearance enhances
      restoration biomimetism principally on the marginal gingiva area. This article
      reviews indications and types of cores designed for natural teeth and implants.

PMID- 17432535
TI  - [Dental ceramics: its history and development].
AB  - This article presents an historical background of dental ceramics. It synthesises
      the evolution of such material and its technical improvements from the stone-age
      to our time. Focusing on the importance of dental aesthetics, it shows the
      investigations realised to upgrade the prosthetic results.

PMID- 17432536
TI  - [The classification of ceramics according to its chemical nature and its method
      of production].
AB  - Nowadays, we find on the market a huge amount of design and manufactured system
      that allows the realisation of all-ceramics restorations, using different
      ceramics. The purpose of this article is suggesting a classification of mostly
      used ceramics and a few laboratory process used in our university.

PMID- 17432537
TI  - [All-ceramic peripheral restorations: crowns and bridges].
AB  - Over the last years, current technologies in dental ceramics are strongly
      improved, constantly producing new materials for the restoration of the single or
      plural teeth. Feldspathic porcelains fused to a cast metal substructure, the so
      called "metal-ceramic crown," has been long time the gold standard; this is
      primarily due to their predictable long-term strength characteristics. All
      ceramic systems are a focus of interest, because they offer aesthetic results
      that may be difficult to achieve with metal-ceramic systems. Nowadays, the new
      ceramics associate aesthetic and good mechanical qualities, biocompatibility,
      accurate marginal fit and low invasive preparations. Thanks to the
      diversification of all-ceram processes, materials properties and clinical
      situations are now the prime criteria which determine the practitioner's choice.
      In this article, we try to summarize different clinical concepts for peripheric
      all-ceram restoration, such as crowns and bridges used in a daily dental
      practice.

PMID- 17432538
TI  - [Bonded porcelain veneers].
AB  - Nowadays the porcelain laminate veneer is a frequently prescribed aesthetic
      restoration for anterior teeth. A substantially reduced tooth preparation is
      required compared to conventional aesthetic complete crown preparations, in
      accord with the practice philosophy of minimally invasive dentistry. The long
      term clinical success of porcelain veneers depends on a careful case selection
      and diagnostic approach, as well as accurate and appropriate tooth preparation
      and adhesive bonding procedures. The goal of this paper is to give a reproducible
      clinical method to the practitioner for the realization of reliable porcelain
      laminate veneers.

PMID- 17432539
TI  - [Cryptosporidium: phylogeny and taxonomy].
AB  - Members of the genus Cryptosporidium in the phylum Apicomplexa were long thought
      to be closely related to the coccidia. However, despite strong morphological
      similarities to these organisms, Cryptosporidium has notable differences with
      them and similarities with the gregarine protozoa. On the basis of phylogenetic
      analysis of molecular data, some authors place Cryptosporidium at the basis of
      the phylum Apicomplexa, others consider species of this genus to be
      phylogenetically too distant from the coccidia and do not include them in this
      group of protozoa, and others think that Cryptosporidium is closely related to
      gregarines. The taxonomy of this genus and the naming of species are undergoing
      rapid change due to the new and increasing molecular information. Molecular
      characterization of oocysts using polymerase chain reaction based procedures has
      not only a major impact on resolving the taxonomy of Cryptosporidium at the
      species level but also on the molecular epidemiology of cryptosporidiosis. Today,
      it is recognized that this genus is a phenotypically and genotypically
      heterogeneous assemblage of largely morphologically identical species and
      genotypes. Fourteen Cryptosporidium species and 21 C. parvum genotypes are
      currently recognized. Phylogenetic analyses have shown that genetically related
      hosts often have related forms of Cryptosporidium. Application of molecular
      techniques to taxonomy and epidemiology is helping to characterize new and
      existing species and determine the sources of the parasites that will facilitate
      the identification of sources of water-borne cryptosporidiosis.

PMID- 17432540
TI  - [Dental caries and fluorosis in children consuming water with different fluoride
      concentrations in Maiquetia, Vargas State, Venezuela].
AB  - The objective of this study was to determine the experience of fluorosis and
      dental caries in 8- 12 year old children that drink water with different fluoride
      concentrations, from Maiquetia, Vargas State. Four hundred and twenty-one
      children were evaluated and divided in groups of 84 children each, according with
      their age (8-9-10-11) but 85 for the age 12. This evaluation was developed by a
      calibrated dentist using Dean's Index for dental fluorosis examining only the six
      upper anterior teeth and DMFT/dmft index to determine dental caries, following
      the criteria established by the WHO. In addition, a social status questionnaire
      was given to the subjects and samples of water and salt from the communities were
      collected. Thirty-three per cent of the children in this study were males and 67%
      were females. Results indicated that the mean DMFT and dmft were 0.91 and 1.88,
      respectively, showing a total of 2.17 teeth with dental caries being the decayed
      component, the highest component observed in both dentitions. The mean prevalence
      of dental fluorosis for the studied population was 16.6%, where the very mild
      category (8.5%) predominated. Maria May was the most affected school with dental
      fluorosis (41.5%) and the fluoride concentration in drinking water after analyses
      was 1.58%. The results of this study indicate the presence of an inverse
      relationship between fluoride concentrations in the water collected at the
      schools and the prevalence of dental fluorosis in the permanent dentition of
      school children, but not in the primary dentition.

PMID- 17432541
TI  - [Evaluation of an antioxidant and mitochondria-stimulating cream formula on the
      skin of patients with stable common vitiligo].
AB  - Vitiligo is a chronic illness of a yet unknown etiology, characterized by an
      acquired and progressive depigmentation of the skin. There are diverse treatments
      for this condition around the world, but up to now, none has been completely
      effective. The objective of this work was to evaluate the application of an
      antioxidant and mitochondrial stimulating formula, of topic use in leukodermic
      areas of patients with stable vulgar vitiligo. A clinical, experimental,
      randomized, double blind study was carried out in 50 male and 50 female patients
      with stable vulgar vitiligo. The patients were distributed in five groups as
      follows: Group 1 (labelled as VitilVenz AF): application of antioxidant and
      mitochondrial stimulating cream and oral administration of antioxidants and
      phenylalanine. Group 2 (labelled as Placebo AF): application of a placebo cream
      and oral administration of antioxidants and phenylalanine. Group 3 (labelled as
      without cream AF): oral administration of antioxidants and phenylalanine. Group 4
      (labelled as Placebo cream): application of a placebo cream. Group 5 (labelled as
      VitilVenz): application of the antioxidant and mitochondrial stimulating cream.
      The following were measured in all patients: the clinical area of newly formed
      pigment every 30 days, during five months; and the presence of melanocytes in the
      histological study, at the beginning and at the end of treatment. The test of
      multiple comparison of Turkey-Kramer was used for the analysis of the results.
      The scheme of treatment that produced the best results was that of the Group 1,
      which consisted of the joint application of the antioxidant and mitochondrial
      stimulating cream and oral administration of antioxidants and phenylalanine (p <
      0.001); followed by Group 5 that only received the topical treatment with the
      antioxidant and mitochondrial stimulating cream. The clinical and histological
      responses of these two groups (1 and 5) were significantly different to the rest
      of the groups. We concluded that the melanocytes in these patients could be in a
      dysfunctional state, product of the formation of free radicals that cause
      cellular and mitochondrial toxicity; and that these free radicals are removed by
      the antioxidant and mitochondrial stimulating elements present in the cream,
      turning the melanocytes functional and producing melanin in the achromic area of
      the vitiligo. This effect would be potentiated by the use of oral antioxidants
      and phenylalanine.

PMID- 17432542
TI  - Differential expression of HSP70 and ultrastructure of heart and liver tissues of
      rats treated with adriamycin: protective role of L-carnitine.
AB  - The anticancer drug adriamycin has been associated to tissular oxidative stress.
      In this regard, the promotion of anti-stress protein synthesis by L-carnitine has
      been suggested in rat adriamycin-induced cardiomyopathy in the long-term.
      However, the citoprotective role of L-carnitine in cardiac and hepatic tissues
      after short-term adriamycin treatment is unknown. HSP70 in the supernatant of the
      homogenized cardiac and hepatic tissues after short-term adriamycin treatment was
      determined by Western blot analysis with and without L-carnitine protection and
      compared to the subcellular characteristics of both tissues by transmission
      electron microscopic analysis. Female Sprague-Dawley rats (n=6), body weight 40
      60 g, were randomized into four groups: control, adriamycin, L-carnitine and L
      carnitine-adriamycin. Saline, adriamycin (15 mg/kg body weight) and L-carnitine
      (20 mg before adriamycin) were given intravenously (0.1 mL). HSP70 accumulation
      was different between the control and the adriamycin samples of both tissues.
      HSP70 was higher in the liver than in the heart both with and without L-carnitine
      protection. The nuclei of heart cells, in the adriamycin group showed alterations
      including, form and irregular perinuclear cysternae with invaginations of
      different sizes that were not observed in the L-carnitine-adriamycin samples.
      Considering the differential expression of HSP70 between liver and heart, our
      results may be important for understanding the role of these proteins in the
      adriamycin-induced distinct levels of organ damage and dysfunction. We suggest
      that L-carnitine exogenous administration might enhance the relationship between
      the cellular energy state and the activation of heat shock response by an unknown
      mechanism. L-carnitine may enhance HSP70 in a cellular-type manner.

PMID- 17432543
TI  - Black Hispanics have a worse cardiovascular risk profile than mixed Hispanics in
      Venezuela.
AB  - In order to characterize components of the metabolic syndrome (MS) in Venezuelan
      black Hispanics and compare these metabolic abnormalities with those found in the
      predominant mixed Hispanic population, 2336 mixed Hispanics (69% women) and 281
      black Hispanics (60% women), aged 20-78 years, without prior history of diabetes
      and/or cardiovascular disease were evaluated in a population-based study in Zulia
      State, Venezuela. Blood pressure (BP), waist circumference, as well as fasting
      insulin, fasting blood glucose (FBG), triglycerides (TG) and high-density
      lipoprotein cholesterol (HDL-C) levels were measured. The criteria proposed by
      the National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP
      III) to identify those with metabolic abnormalities were used. We found that
      black Hispanics showed higher frequency of age-adjusted elevated BP than mixed
      Hispanics in both men (66.9% vs. 52.3%, p < 0.01) and women (39.3% vs. 30.4%, p <
      0.05). In men, elevated FBG was also more frequent in black Hispanics (32.7%)
      than in mixed Hispanics (22.3%), despite the lack of significant differences in
      fasting insulin, HOMA-insulin resistance and HOMA-beta cell function values. In
      women low HDL-C and higher abdominal obesity were more common in black Hispanics
      (71.8% and 54.1%, respectively) than in mixed Hispanics (56.2% and 44.5%,
      respectively), despite the greater frequency of high TG in mixed Hispanics
      (22.6%) when compared to black Hispanics (13.3%). Furthermore, in logistic
      regression analysis black Hispanic race was independently associated with higher
      risk for hypertension, fasting hyperglycemia, and low HDL-C. These results
      suggest that black Hispanics have worse cardiovascular risk profile than mixed
      Hispanics in Zulia State, with higher BP, higher FBG, more abdominal obesity, and
      lower HDL-C. Identification and intervention of these high-risk subjects are
      important strategies for diabetes and cardiovascular disease prevention in
      Venezuela.

PMID- 17432544
TI  - [Obtention of a heterohybridoma for production of type IgM monoclonal antibodies
      against the D antigen of the Rh system].
AB  - The objective was to obtain a heterohybridoma capable of producing a monoclonal
      antibody with IgM type anti-D specificity (Rh system), that could be used as a
      reactive for hemoclasification. Mononuclear cells (MNC) were extracted from a
      blood sample of a highly sensitized woman, five days after giving birth to an Rh
      positive child. These were then transformed with the culture supernatant (CSN) of
      B05.8 cells, rich in Epstein Barr virus (EBV). Once transformed and in
      exponential growth, they were fused with K6H6/B5 line cells using PEG 4.000 as a
      fusing agent in a 1:1 proportion. After fusion, they were seeded in culture
      plates in order to evaluate the formation of hybrids and the secretion of
      specific antibodies in the CSN of each well. The efficiency of the fusion was 1.8
      x 10(-6), making it possible to obtain an anti-D IgM producing clone, which we
      named BMS-9. This clone could be maintained in constant culture for three months,
      producing antibodies in a concentration of 4 microg/mL in de CSN. It was also
      possible to obtain antibodies with an Artificial Capilar System (ACS) reaching a
      concentration of 24 microg/mL. Potency was determined using Ror cells. In CSN at
      immediate centrifugation (IC): 1 x 32, score 52; 15' from incubation at room
      temperature (RT): 1 x 1,024 score 105. With that ACS product at IC: 1 x 32 score
      54; 15' from incubation at RT: 1 x 8.192 score 136; and a 37 degrees C: 1 x 8,192
      score 136. Reactivity was detected with red cells D(IIIa), D(IV), D(Va), D(VI)
      type IV, D(VII), DFR, DNU, STEM+, DAR and DAU. There was no reactivity with red
      cells D(IIIc), DI(Va), D(V) type II, D(VI) types I, II y III, Ro(HAR), DOL and
      weak D type II. During field study, no false negative or false positive reactions
      were detected. A stable heterohybridoma was obtained, producer of IgM type anti
      D, with enough qualities to be used in blood typing. Given the excellent
      qualities of the antibody, we are evaluating dilution media and the addition of
      type IgG antibodies in order to manufacture a reactive for use in
      hemoclassification.

PMID- 17432545
TI  - [Frequency and clinical implications of lupus anticoagulant in patients with
      terminal chronic renal failure in hemodialysis].
AB  - The objective of the present study was to determine the frequency of lupus
      anticoagulant (LA), in patients with terminal chronic renal failure (TCRF), and
      its association with thrombotic events. Sixty three patients were separated into
      two groups: Group A, consisted of 32 patients under treatment with hemodialysis,
      and Group B was formed of 31 patients who were treated in a conservative manner.
      Presence of LA was found in 4 patients from Group A and none from Group B. Seven
      thrombotic events were registered, all in patients from Group A, and three of the
      episodes happened in 2 patients with LA, showing a statistically significant
      difference with LA negative patients from the same Group A (p < 0.001). Three of
      the LA positive patients suffered from type 2 diabetes and all of them had been
      under dialysis for less obtained by than 6 months. Vascular access was
      catheterization which means that 57.1% of patients with this type of procedure
      were positive for LA. The present results show a strong relationship between the
      presence of LA and thrombotic episodes in patients with TCRF, under hemodialysis
      with the use of catheter, instead of a permanent vascular access. Due to the fact
      that prolonged use of catheters for hemodialysis has been related to positive LA,
      it is advisable to screen patients under dialysis for the presence of this
      antibody, and to promote the prompt availability of a permanent vascular access,
      in order to prevent complications, such as thrombosis.

PMID- 17432547
TI  - Analysis of CFTR gene mutations and cystic fibrosis incidence in the Ecuadorian
      population.
AB  - Ecuador is one of the Latin American countries where cystic fibrosis has not been
      thoroughly studied. The goal of this study was to establish the incidence of this
      specific pathology and the incidence of the 29 most common European CF mutations
      in Ecuador's population. We performed a prospective-descriptive study with the
      intention of including patients registered at the Ecuadorian Cystic Fibrosis
      Foundation as well as the main pediatric hospitals in Ecuador. The inclusion
      criteria were clinical manifestations of cystic fibrosis plus two positive
      pilocarpine iontophoresis sweat tests (CI >60 mEq/L). We tested F508del mutation
      by heteroduplex method and then, we confirmed these results and searched for
      other 28 frequent European-mutations aside from F508del by a reverse dot blot
      technique (INNO-LiPA CFTR 29 + Tn). Sixty two unrelated patients were included.
      Both heteroduplex and reverse dot blot methods identified 53.22% of all
      mutations. The estimated Ecuadorian cystic fibrosis incidence was 1:11,252. The
      mutations found and their incidence were F508del (37.1%), G85E (8.9%), G542X
      (2.4%), N1303K (2.4%), G551D (1.6%) and R334W (0.8%). The incidence of cystic
      fibrosis in Ecuador is closely similar to other Latin American countries where
      there is a large "mestizo" population. We are reporting one of the highest
      incidences of G85E in the world.

PMID- 17432546
TI  - [Protective effect of melatonin and sodium thiosulphate on histopathology and
      ultrastructure of the kidney in rats with acute paraquat poisoning].
AB  - Paraquat (PQ) toxicity produces severe injures in many major organs systems,
      including kidney, developing renal failure with fatal evolution in most of the
      cases. Several antidotes have been used in the treatment of paraquat intoxication
      without satisfactory results. The antioxidative effect of melatonin (MLT) and
      sodium thiosulphate (STS) on kidney in rats with acute intoxication by PQ was
      studied. Forty male Wistar rats were used, divided in 4 groups of 10 rats each.
      Group I, control, was injected intraperitoneally (ip) with 1 ml of saline
      solution; group II, received DL50 of PQ, ip; groups III and IV, DL50 of PQ, and
      simultaneously the first dose of MLT (15 mg/kg, ip) or STS (1,5 g/kg, i.p.)
      respectively. Thirty minutes later, groups III and IV received a second similar
      dose of MLT and TSS. After 24 hours, rats were sacrificed with pentobarbital, and
      kidneys were extracted for morphological study. Light and electronic microscopy
      observations showed in group II morphological changes of acute tubular necrosis
      in proximal tubule in group II, similar findings, with lesser magnitude, were
      observed in the animals treated with the antidotes, suggesting a partial
      protection. In conclusion, individual use of MLT and STS at the doses and time
      used partially prevent damage caused by paraquat to the cell. In consequence,
      more experiments with these drugs are necessary to considere them as specific
      treatments in cases of poisoning by paraquat.

PMID- 17432548
TI  - [Diagnosis and treatment of methylmalonic aciduria: a case report].
AB  - The methylmalonic aciduria is an organic acidemia, inherited as autosomic
      recessive trait, caused by a deficiency of the methylmalonyl-CoA mutase, or by
      defects in the biosynthesis of the cofactor adenosylcobalamin. Regarding the
      enzymatic defect, there are two forms: mut(o) with no detectable enzymatic
      activity and mut(-) with reduced activity. Its clinical presentation may vary
      from a severe neonatal form with acidosis and death, up to a progressive chronic
      form. Here we describe the case of a four year-old boy, with diagnosis of
      methylmalonyl-CoA mutase deficiency type mut(-) with an acute presentation.
      Molecular analysis of MUT gene identified two mutations c.607G>A (G203R) and
      c.2080C>T (R694W), later confirmed in the parents. The aim of this report is to
      highlight the importance of including the organic acid analysis in urine among
      the first line exams in acutely and severely ill children with undefined
      etiology. The definitive diagnosis is important because it may allow a specific
      treatment and a favorable evolution to prevent the secuelae.

PMID- 17432549
TI  - [Immune-testicular regulation and cytokines].
AB  - The pathogenesis of male infertility can be reflected in alterations of
      spermatogenesis caused by testicular cancer, aplasia of the germinal cells,
      varicocele, environmental factors or defect in the transport of the sperms, among
      others. In general, 48% of men suffer unexplained infertility. During a long
      time, the masculine reproductive tract and the immune system have been studied as
      different and independent systems. However, in the last two decades a particular
      interest has arisen in the interaction of both systems on masculine infertility,
      in particular in the evaluation of antisperm antibodies as a common cause of
      infertility. Also, the inflammation due to genital or systemic infections can
      cause alterations in the testicular function. The recognition of intratesticular
      antigens provokes the production of antibodies by B lymphocytes. Then, the immune
      system induces a cellular response, by cytokines secretion, activation of
      complement and T lymphocytes activation. In this review the components and the
      immune system response mechanism, the organization of the testicle as a
      reproductive organ and the mediators of the immunologic response will be
      examined: interleukin-1 (IL-1), IL-6, leukaemia Inhibitory factor, tumor necrosis
      factor-alpha, the molecule FasL (CD95L) and Fas (CD95), macrophage migration
      inhibitory factor, mononuclear phagocyte colony stimulating factor,
      Granulocyte/macrophage colony stimulating factor, as well as stem cell factor,
      interferon, transforming growth factor B and activins.

PMID- 17432550
TI  - Epidemiology of prostate cancer.
AB  - Prostate cancer is one of the most important cancers in men. With a worldwide
      incidence of 25.3 per 100,000 it is the second most common cancer in men, with
      large differences between countries. Important clues on risk factors remain to be
      found. Age, genetic factors and environmental influences have been studied.
      Incidence has been increasing over the last few decades, largely due to early
      detection procedures. The mortality rate of 8.1 per 100,000 mainly affects men at
      older ages; increases in this rate over time and differences between countries
      are markedly smaller than for incidence. For the future, prostate cancer will
      remain an important and--through evolutions in incidence and demography--growing
      health problem.

PMID- 17432551
TI  - Natural history of prostatic carcinoma: the pathologist's perspective.
AB  - The stem (basal) cells of prostate acini are considered the origin of prostate
      cancer. Between these cells and the final secretory cells, different intermediate
      or transit cells can be observed, and every one of them can evolve into malignant
      cells, explaining the biological variability of prostatic cancer. The exact
      changes between normal gland and prostatic intraepithelial neoplasia (PIN) are
      not yet known, but a post-inflammatory atrophy lesion is being studied in this
      respect. The PIN lesion is considered the pre-invasive change of prostatic cancer
      and its presence in needle biopsy is clinically used for follow-up of the
      patient. The progressive knowledge of the stromal invasion in prostate cancer
      (loss of some cell-cell adhesion molecules and expression of others) can be
      correlated with the Gleason grading system, and the molecular changes in the
      progression to androgen-independent carcinoma can be used as a prognostic marker
      in conjunction with the classical pathological markers.

PMID- 17432552
TI  - Prognostic factors in prostate cancer.
AB  - In the nineteenth century the main goal of medicine was predictive: diagnose the
      disease and achieve a satisfying prognosis of the patient's chances. Today the
      effort has shifted to cure the disease. Since the twentieth century, the word
      prognosis has also been used in nonmedical contexts, for example in corporate
      finance or elections. The most accurate form of prognosis is achieved
      statistically. Based on different prognostic factors it should be possible to
      tell patients how they are expected to do after prostate cancer has been
      diagnosed and how different treatments may change this outcome. A prognosis is a
      prediction. The word prognosis comes from the Greek word (see text) and means
      foreknowing. In the nineteenth century this was the main goal of medicine:
      diagnose the disease and achieve a satisfying prognosis of the patient's chances.
      Today the effort has shifted towards seeking a cure. Prognostic factors in
      (prostate) cancer are defined as "variables that can account for some of the
      heterogeneity associated with the expected course and outcome of a disease".
      Bailey defined prognosis as "a reasoned forecast concerning the course, pattern,
      progression, duration, and end of the disease. Prognostic factors are not only
      essential to understand the natural history and the course of the disease, but
      also to predict possible different outcomes of different treatments or perhaps no
      treatment at all. This is extremely important in a disease like prostate cancer
      where there is clear evidence that a substantial number of cases discovered by
      prostate-specific antigen (PSA) testing are unlikely ever to become clinically
      significant, not to mention mortal. Furthermore, prognostic factors are of
      paramount importance for correct interpretation of clinical trials and for the
      construction of future trials. Finally, according to WHO national screening
      committee criteria for implementing a national screening programme, widely
      accepted prognostic factors must be defined before assessing screening.

PMID- 17432553
TI  - The prevention of prostate cancer.
AB  - From our better understanding of the natural history of prostate cancer, it is
      not unreasonable to believe that the disease is preventable. Prostate cancer has
      become a major healthcare problem worldwide, as life expectancy increases.
      Moreover, the cancer is slow growing, with a period of about 20-25 years from
      initiation to the stage when the clinically detectable phenotype can be
      identified. This review provides a simple overview of the endocrinology of
      prostate cancer and discusses some of the pharmaceutical agents that have been or
      are being tested to restrain, possibly arrest, the progression of this slowly
      growing cancer. Also discussed are many of the dietary factors that may influence
      the molecular or endocrine events implicated in its development. Dietary factors
      are considered responsible for the geographical differences in prostate cancer
      incidence and mortality. Since about 50% of all men worldwide, from both East and
      West, show evidence of microscopic cancer by 50 years of age, growth restraint
      would appear to be the pragmatic option to the possibility of preventing
      initiation.

PMID- 17432554
TI  - Prostate cancer screening.
AB  - Prostate cancer incurs a substantial incidence and mortality burden, similarly to
      breast cancer, and it ranks among the top ten specific causes of death in the
      United States. It is inherent as we maximize the detection of early prostate
      cancer that we increase the detection of both nonaggressive (slow growing) and
      aggressive (faster growing) prostate cancers. The evidence clearly supports the
      use of PSA screening in conjunction with DRE as a means of early detection of
      prostate cancer. Widespread implementation of prostate cancer screening in the
      United States has led to the phenomenon of stage migration with more cancers
      being detected at a lower stage. Such a trend has decreased the incidence of
      metastatic disease at diagnosis and paralleled the decrease of the mortality rate
      from prostate cancer. Our understanding of the natural history of prostate cancer
      is progressing over time, but the question of its length is unanswerable. The
      relatively long doubling time (on average) of early prostate cancer of 3 to 4
      years or more indicates a relatively good prognosis for many men with this
      disease, even without early detection and treatment. Unfortunately, the poor
      specificity of the PSA test in men with benign prostatic hyperplasia (BPH) leads
      to high rates of prostate biopsy and attendant illnesses and costs. Early
      detection is more apt to detect a slow-growing prostate cancer than a faster
      growing cancer that is associated with a more rapid course of progression to
      metastatic disease. Hence, the launching of mass screening programs for the early
      detection of prostate cancer is premature. However, in the absence of solid
      evidence of benefit, one reasonable approach to screening at the individual level
      is to involve the patient in decisions about whether or not to perform a PSA
      test. Thus, "offering" PSA testing must be accompanied by informed discussion
      within the context of an ongoing patient-physician relationship. This is to be
      distinguished from the use of PSA testing for the purpose of "mass screening."
      Concepts that must be explored with the patient include: 1. The long-term
      ramifications of screening 2. The relatively high probability of further
      evaluation and biopsy with positive results 3. Potentially difficult decisions
      that may arise about using treatments that are associated with considerable
      morbidity and uncertain benefits (at the time) if cancer is discovered We should
      identify a future path that is evidence-based, focused on the issues that make a
      difference to patients, and results in better and longer lives of those with the
      disease and those who are at risk of getting it. If that path leads to treating
      fewer patients in the future, even if sometimes more aggressively, we should
      pursue it definitely and consequently.

PMID- 17432555
TI  - Diagnosis of prostate cancer.
AB  - The contemporary challenge of prostate cancer diagnosis has been changed in the
      past decade from the endeavor to increase detection to that of detecting only
      those tumors that are clinically significant. Better interpretation of the role
      of prostate-specific antigen (PSA) and its kinetics as a diagnostic tool, the
      adoption of extended prostate biopsy schemes, and perhaps implementation of new
      transrectal ultrasound (TRUS) technologies promote the achievement of this
      clinical mission. This chapter reviews these issues as well as the change in
      practice of patient preparation for TRUS-biopsy and analgesia during it, the role
      of repeat and saturation prostate biopsies, and the interpretation of an
      incidental prostate cancer finding. Currently, the lifetime risk of a diagnosis
      of prostate cancer for North American men is 16%, compared to the lifetime risk
      of death from prostate cancer, which is 3% (Carter 2004). The advent of prostate
      specific antigen (PSA) screening and transrectal ultrasonography (TRUS) has
      significantly impacted the detection of prostate cancer over the last 20 years.
      The mean age at diagnosis has decreased (Hankey et al. 1999; Stamey et al. 2004)
      and the most common stage at diagnosis is now localized disease (Newcomer et al.
      1997; Stamey et al. 2004). The goal of prostate cancer screening is to detect
      only those men at risk for death from the disease at an early curable phase. The
      ambiguous natural history of this most common malignancy in men, being latent
      with questionable life-threatening potential in a large number of cases on the
      one hand, with only a relatively small number (though not negligible) of highly
      malignant cases on the other, propels many doubts about whether this is possible.
      This was famously phrased more than 20 years ago by Whitmore who asked: "Is cure
      possible for those in whom it is necessary; and is it necessary for those in whom
      it is possible?" This is probably even more relevant nowadays. During the past
      decade two factors influenced significantly the increased detection rate of
      prostate cancer in general and that of clinically insignificant prostate cancers
      in particular: the widespread use of serum PSA as a screening tool to a large
      extent and to a lesser though significant extent the application of extended
      multiple core biopsy schemes (Master et al. 2005). In fact, 75% of men in the
      United States aged 50 years and older have been screened with the PSA test
      (Sirovich et al. 2003). Outside of the screening context, which is dealt with in
      depth in Chap. 5, clinical suspicion of prostate cancer is raised usually by
      abnormal digital rectal examination (DRE) and/or by abnormal levels of serum PSA.
      Final diagnosis is achieved only based on positive prostate biopsies.

PMID- 17432556
TI  - Does localized prostate cancer exist?
AB  - Does localized prostate cancer exist, and how do we diagnose it? Early diagnosis
      and screening programs for prostate cancer (PC) have led to a greater proportion
      of patients with a low-stage disease at diagnosis. More men are treated with
      curative intent by radical prostatectomy (RP), external beam radiotherapy, or
      brachytherapy. However, a substantial percentage of patients still experience a
      prostate-specific antigen (PSA) relapse within 5 years. Biochemical recurrence is
      observed in approximately 40% of patients who undergo RP, with 95% of those
      relapses in the first 5 years. To avoid the risk of recurrence, the recent
      tendency has been to detect PC at a lower PSA level than the level widely
      accepted (> or = 4.0 ng/ml). But the risk of overdiagnosis and overtreatment is a
      real problem in the PSA era. Discussion around the wide discrepancy between the
      high prevalence of histological changes recognizable as cancer and the much lower
      prevalence of clinical disease is prominent. The recent experience from studies
      on watchful waiting and the results of randomized trials between surgery and
      active surveillance have clearly demonstrated that many localized PC are
      overtreated. New screening and management strategies are required to target
      aggressive disease at an early stage while avoiding overdiagnosis and
      overtreatment.

PMID- 17432557
TI  - Staging of prostate cancer.

PMID- 17432558
TI  - Guidelines and counselling for treatment options in the management of prostate
      cancer.
AB  - Prostate cancer is often a complex disease and one in which many aspects of the
      disease and the affected patient must be taken into consideration before
      decisions about diagnostic work-up, treatments, follow-up, etc. can be made. The
      current chapter reflects the current recommendations of the European Prostate
      Cancer Guideline Group made on the basis of criteria of evidence-based medicine
      after extensive review of the literature available up to December 2005.

PMID- 17432559
TI  - Choices for surgery.
AB  - Surgical treatment of prostate cancer has seen many improvements in the past two
      decades, including laparoscopy, robotic surgery, and better assessment of quality
      of life and functional results. The limits of surgery for locally advanced
      disease and after failure of radiotherapy have been better defined, together with
      the roles of neoadjuvant and adjuvant treatment. Patients with clinically organ
      confined prostate cancer, reasonable life expectancy, and little or no co
      morbidity are the best candidates for radical prostatectomy. This chapter reviews
      the different technical options for the treatment of prostate cancer, with their
      respective indications and functional and oncological results.

PMID- 17432560
TI  - Radiation therapy in prostate cancer.
AB  - Adenocarcinoma of the prostate is one of the most frequently diagnosed cancers of
      men in the Western hemisphere and is second only to lung cancer for male cancer
      mortality. Most patients are diagnosed in the early/clinically localized stage,
      which can be treated curatively with radiation therapy alone. Innovative methods
      such as brachytherapy, three-dimensional conformal radiotherapy (3D-CRT), and
      IMRT (intensity modulated radiotherapy) are able to deliver very high tumoricidal
      doses to the diseased prostate, with minimal side effects to the surrounding
      tissue. Radiation therapy combined with hormonal treatment can be curative in
      locally advanced disease. Radiation therapy is also very effective in alleviating
      symptoms of metastatic prostate cancer (bone metastases, spinal cord compression,
      and bladder outlet obstruction).

PMID- 17432561
TI  - Cryoablation and high-intensity focused ultrasound.
AB  - The fight against prostate cancer goes beyond radical prostatectomy, radiation
      therapy, and hormonal therapy. Temperature can also kill cells and proves to be
      highly successful in this war on prostate cancer. There is no known insensitivity
      to extremely low or extremely high temperatures.

PMID- 17432562
TI  - The role of hormonal treatment in prostate cancer.
AB  - In 1941 Huggins and Hodges published for the first time the favorable effects of
      surgical castration and estrogen treatment on the progression of metastatic
      prostate cancer. However, this hormonal therapy is not without side effects.
      Since this pioneering milestone in history of prostate cancer, a further
      tremendous innovation did not take place. Today, due to intensive clinical,
      biochemical, nuclear-biological and molecular-biological research, many hormone
      active treatment variations are available. Besides traditional hormonal therapy,
      surgical or chemical castration, maximal androgen blockade, nontraditional forms
      of hormonal therapy, intermittent hormonal therapy, antiandrogens, 5-alpha
      reductase inhibitors, and their combinations, we discuss options toward creating
      an increased number of side effect-oriented offers of hormonal treatment options,
      guaranteeing a longer and more comfortable exhaustion of the individual hormonal
      period of response and probably a longer survival. The prerequisite is a closer
      than-ever monitoring by tumor marker and an early observation of symptomatic
      changes.

PMID- 17432563
TI  - Androgen-independent prostate cancer.
AB  - Androgen-independent or hormone-refractory prostate cancer (AIPC) is prostate
      cancer that progresses after primary androgen-ablation therapy--either
      orchiectomy or a gonadotropin-releasing hormone (LHRH) agonist, followed by
      addition and subsequent withdrawal of an antiandrogen. In the majority of
      patients, AIPC appears after a median time of 18 months of hormone deprivation.
      Patients with AIPC have a median survival between 10 and 20 months and the
      prognosis can be defined by using nomograms. Standard treatment is continued
      castration by LHRH agonists in combination with docetaxel-containing
      chemotherapy. Other treatment options to palliate symptoms are hormones, other
      chemotherapeutic agents, radioisotopes or radiotherapy and bisphosphonates. New
      targeted drugs and vaccination strategies are evaluated in the treatment of AIPC.

PMID- 17432564
TI  - Prostate cancer treatment and quality of life.
AB  - Prostate cancer is detected today at earlier stages and in younger men than ever
      before. A lot of men are asymptomatic and also physically and sexually active at
      diagnosis, and most of them are being treated by curative procedures. These
      trends have led to increasing numbers of patients undergoing disease management
      for longer periods of time. For many patients quality of life (QoL) may be just
      as important as survival. Thus, QoL considerations may well be the critical
      factor in medical decision-making for most of them. Widespread interest in
      studying patient-centred outcomes has led to the development of methods for
      health-related QoL measurements. In fact, many questionnaires have been
      introduced in clinical practice to assess the impact of QoL in patients (SF-36,
      CARES, FACT, EORTC QLQ-C30, GRISS, UCLA PCI, PCOS). Herein we evaluate the impact
      of QoL on patients affected by prostate cancer and treated with watchful waiting,
      radical prostatectomy, radiotherapy and hormonal therapy; we have also considered
      the role of supportive care, including the administration of analgesics,
      antidepressants, corticosteroids, bisphosphonates, antiemetics and stool
      softeners, together with psychological support. The ultimate goal of QoL research
      should strongly improve medical care and concretely assist patients and
      physicians in treatment decision-making.

PMID- 17432565
TI  - Europa Uomo: the European Prostate Cancer Coalition.
AB  - Europa Uomo is a patient-led, non-governmental association (NGO), launched
      formally in Milan in 2004 with a legal base in Antwerp. As a coalition of
      prostate cancer patient groups with representation in 18 European countries, the
      NGO focusses on awareness, early detection, optimal treatment, multi-professional
      care and, above all, quality of life and patient advocacy. In the majority of
      European countries prostate cancer is the most commonly diagnosed cancer
      affecting men beyond middle age. The incidence and substantial mortality rises
      with age, peaking in the seventh decade. Standards of diagnosis and treatment
      vary across Europe and attitudes differ. Information about the early detection
      and awareness of prostate cancer available to the public leaves much to be
      desired. Since 2002, involved individuals, patient support groups, patients,
      family members, physicians, urologists, oncologists and nurses joined in the
      formation of an independent, international, non-profit association of patient-led
      prostate cancer support groups from European countries known as Europa Uomo, the
      European Prostate Cancer Coalition. This Coalition was legally established as an
      NGO in June 2004 in Milan with the headquarters and secretariat in Antwerp,
      Belgium. Its membership represents 18 countries by the national or regional
      groups listed in Table 16.1 with their respective contact persons. The coalition
      is led by a steering committee under the control of the annual general assembly.
      The steering committee members and their co-ordinates are listed in Table 16.2.
      Scientific advice is given by a scientific committee chaired by Prof. H. Van
      Poppel as the liaison officer with the European Association of Urology (EAU). The
      support for EAU guidelines appears on the Web site and will be linked to all
      members in their own language (www.cancerworld.org/europauomo). The goals and
      activities of Europa Uomo have been condensed in a series of slides at the
      request of the Eurocan+Plus collaboration to facilitate international
      collaboration. These slides have been listed in Tables 16.3, 16.4 16.5, 16.6,
      16.7, 16.8, 16.9, 16.10, 16.11, 16.12, 16.13 and 16.14. It should be noted that
      membership includes supporting activities for patients and adherence to our 10
      objectives listed in the manifest (Tables 16.4-16.6). The bottom line is that the
      coalition focuses on peer-to-peer support, information and education, as well as
      partnership with professional associations. We in Europa Uomo hope to see the
      decrease in over-treatment and mortality of prostate cancer by the clinical
      activities, trials and research of the professional organizations. We have the
      great opportunity to be supported and sponsored by the European School of
      Oncology (ESO) and its director Dr. A. Costa. The European Society of Medical
      oncology (ESMO), the International Consultation of Urological Diseases (ICUD) and
      the International Prostate Health Council (IPHC) support our advice on scientific
      data. It is quite natural that all of our members have joined the European Cancer
      Patients Coalition (ECPC) to speak for all European patients with one voice. We
      are a young association but ambitious enough to launch several projects in
      addition to the Web site, such as the Prostate Passport, a global coalition of
      patient support organizations, and a series of patient symposia. In this way we
      are able to show our support and collaboration with all health workers, including
      nurses, social workers, nutritionists and psychologists. We like to conclude this
      contribution with a list of questions to the experts from our participation in
      the 6th International Consultation of Urological Diseases (ICUD) symposium in
      Paris (Hudson et al. 2006).

PMID- 17432566
TI  - [Studies on single-cell analysis].
AB  - The single-cell analysis is a frontier field of sciences that has been developed
      from the interdisciplinary collaborations of analytical chemistry, biology and
      medicine. At the present time, the great achievements in the application of
      capillary electrophoresis and microfluidic chip to single-cell analysis,
      particularly, in the application of microfluidic chip to culture, manipulation,
      location, separation and detection of components of single cells, real-time
      detection of secretion from single-cells and high-throughput array detection have
      been made. The unit procedures can be made up in any device in accordance with
      the requirements. In this paper, the work of the author's group is presented
      mainly. In addition, the developments of the capillary electrophoresis and chip
      electrophoresis applied to single-cell analysis in recent years are reviewed. The
      prospects for single-cell analysis including capillary electrophoresis and
      microfluidic chip, measurement and control at the cell-chip interface, and
      quantum dots for probing live cells are also proposed.

PMID- 17432567
TI  - [Characterization of surface properties of 1,3,5-triamino-2,4,6-trinitrobenzene
      by inverse gas chromatography].
AB  - The surface properties of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) with
      various particle sizes were characterized by inverse gas chromatography (IGC).
      The disperse component gamma s(d) of surface free energy of TATB samples
      increased as temperature increased. The larger the particle size is, the quicker
      the increasing rate of the disperse component will be as the temperature
      increases. The gamma s(d) of the coarse TATB is the highest (193.2 mJ/m2) and
      that of the submicron TATB is the smallest (64.0 mJ/m2) at 353 K. Due to the
      different preparation processes and particle sizes, the samples show obviously
      different Lewis acid-base properties. Fine TATB can provide positive Lewis acid
      base active sites and has higher acidity. The specific components of the
      adsorption of polar probes on the surface of the other three types of TATB were
      found to be endothermic owing to the strong hydrogen bond of inter- and intra
      TATB molecules. Their surface acidity and basicity constants, K(a) and K(b) are
      negative.

PMID- 17432568
TI  - [Determination of amphetamines in human hair using dynamic liquid-phase
      microextraction and gas chromatography/selected ion monitoring-mass spectrometry
      after microwave derivatization].
AB  - Human hair is an important specimen for drug abuse analysis owing to its easy
      collection, long surveillance time window and good correlation between the
      "degree of addiction" and actual drug concentration. A simple method for
      determination of 4 amphetamines in human hair was developed. The hair was
      digested under basic condition, and the drugs in it were extracted using
      microvolume of chloroform. The organic layer was then transferred into another
      tube to be derivatized with N-methyl-bis (trifluoroacetamide) (MBTFA) by
      microwave heating. Finally the reacted solution was detected by gas
      chromatography/selected ion monitoring-mass spectrometry (GC/SIM-MS) directly. 2
      Methyl-phenyl ethylamine was used as an internal standard. Good linearities were
      obtained for 4 amphetamines with correlation coefficients better than 0.996. The
      limits of detection, based on a signal-to-noise ratio (S/N) of 3:1, were all
      about 50 pg/mg for amphetamine (AM) , methamphetamine (MAM), methylenedioxy
      amphetamine (MDA), and methylenedioxy-methamphetamine (MDMA) in hair. The
      reproducibility of the method was satisfactory, with the relative standard
      deviations of 6.0% for AM, 13.9% for MAM, 10.2% for MDA and 9.2% for MDMA. Some
      real hair from the drug abusers was analyzed with this method. The minimal hair
      is less than 5 mg (about 20 cm). The method is highly sensitive, easy to operate,
      time-saving and economic, which can be used for trace analysis of amphetamines in
      human hair.

PMID- 17432569
TI  - [Determination of dioxins by gas chromatography-mass spectrometry coupled with
      large volume injection].
AB  - The common analytical instrument for dioxin analysis/determination is gas
      chromatograph (GC) coupled with an electron capture detector (ECD), a flame
      ionization detector (FID), and a mass spectrometer (MS) , etc. Generally, since
      the concentration levels in environmental samples are pg/g or pg/L, it requires a
      very high resolution and sensitivity for the analytical system. To solve the
      problem one way is to increase the amount of a sample, however, which can
      significantly increase the pretreatment work load. The other way is to increase
      the injection volume. In this paper, a method for dioxin determination was
      developed using GC-MS coupled with the large volume injection (LVI). Under the
      condition of maintaining the same amount of solute, the comparison was studied
      for the changes of peak areas and peak widths by the injection of different
      volumes from 1 to 100 microL. The results showed that the peak area and peak
      width did not have obvious changes, and the separation performance was not
      affected compared with the traditional split/splitless injection. The detection
      limits obtained are improved by 1 - 2 orders of magnitude over those using
      split/splitless injections. Once the operation conditions are optimized, LVI is
      more flexible in handling samples of wide concentration ranges than the
      traditional split/splitless inlet approach.

PMID- 17432570
TI  - [Determination of pyrethroid pesticide residues in tobacco leaves and tea using
      stir bar sorptive extraction-thermal desorption and gas chromatography-mass
      spectrometry].
AB  - A novel method for the determination of 5 pyrethroid pesticide residues in
      tobacco leaf and tea samples was established. The pesticide residues in the
      samples were extracted and concentrated with stir bar, desorbed by thermal
      desorption system, and then determined by gas chromatography-mass spectrometry
      (GC-MS). The pesticide residues in the samples were extracted with a stir bar at
      1 100 r/min for 1 h. The desorption was carried out at 300 degrees C for 4 min
      under a helium flow of 50 mL/min while maintaining a cryofocusing temperature of
      0 degrees C in the CIS-4 injector of the GC-MS system. Finally, the CIS-4
      injector was raised to a temperature of 300 degrees C and then the analytes were
      separated by GC and detected by MS. The limits of detection of this method for
      the tobacco leaves ranged from 3.3 ng to 11.4 ng. The recoveries of pesticides
      from the tobacco leaves ranged from 94.8% to 103.4% and the relative standard
      deviations (RSDs) of peak areas ranged from 5.3% to 8.6% (n = 6). The limits of
      detection of this method for tea ranged from 4.2 ng to 10.5 ng. The recoveries of
      pesticides from tea ranged from 98.2% to 110.1% and the RSDs of peak areas were
      less than 9.6% (n = 6). Therefore, this method can satisfy the requirements for
      the rapid analysis of pesticide residues in the tobacco leaf and tea samples.

PMID- 17432571
TI  - [Determination of neutral chemical constituents in flue-cured tobacco by
      comprehensive two-dimensional gas chromatography and time-of-flight mass
      spectrometry].
AB  - A method was established to analyze neutral chemical constituents in tobacco
      accurately by comprehensive two-dimensional gas chromatography and time-of-flight
      mass spectrometry (GC x GC-TOFMS). A DB-Petro column (50 m x 200 microm x 0.5
      microm) was chosen as the column for the first dimension, and a DB-1701 column
      (2.3 m x 100 microm x 0.1 microm) was chosen as the column for the second
      dimension. The modulation period was set at 8 s, and the column pressure was 550
      kPa. The initial temperatures of the two columns were set at 80 degrees C and 85
      degrees C respectively and then increased with temperature programming. The
      contents of the neutral chemical constituents in different positions of tobacco
      leaves, product regions and varieties of tobacco were compared. The results
      showed that the total contents of the 24 neutral fractions in the middle leaves
      was the most, then in the upper leaves and the least in the lower leaves. These
      contents in the flue-cured tobacco produced by Brazil was the highest, followed
      by Zimbabwe, Yunyan85, Zhongyan101, NC89 and K326. In four kinds of tobacco, the
      total contents of the 24 neutral fractions in Oriental tobacco was the highest,
      followed by Burly tobacco, Flue-cured tobacco and Maryland tobacco.

PMID- 17432572
TI  - [Application of single drop microextraction in the determination of phthalate
      esters in food by gas chromatography-mass spectrometry].
AB  - A novel, simple, fast and environment-friendly method based on single drop
      microextraction (SDME) was developed for the determination of phthalate esters in
      food by gas chromatography-mass spectrometry (GC-MS). The effects of the nature
      of organic solvents, microdrop volume, the depth of microdrop in sample solution,
      extration time and stirring rate on the extraction efficiency were investigated
      separately. The optimal SDME conditions, 2.0 microL of toluene, 0.75 cm of the
      depth of microdrop, 1 000 r/min of stirring rate and 20 min of extraction time,
      were obtained and used for the analysis of dimethyl phthalate (DMP), diethyl
      phthalate (DEP), di-n-butyl phthalate (DBP), dioctyl phthalate (DOP) and
      diethylhexyl phthalate (DEHP) in food. At first, a sample was dissolved with de
      ionized water and then extracted with ultrasonication for 15 min. Then, it was
      filtrated and the solution was extracted and concentrated by a single drop of a
      solvent. Finally, it was analyzed by GC-MS. The reproducibility, linearity,
      recovery, and limit of detection of the method were studied. The results showed
      that the limits of detection (LOD) were between 25 ng/L and 0.8 mg/L. The overall
      recoveries were 87.1% - 114.4% with the relative standard deviations of 4.9% -
      11.6%. This method has been successfully applied to the analysis of food samples.

PMID- 17432573
TI  - [Determination of isopropylthioxanthone residue in milk migrated from packaging
      materials by gas chromatography-mass spectrometry].
AB  - Isopropylthioxanthone (ITX) has been widely used as the photoinitiator in
      printing ink of packaging materials in modern food packaging industry. A method
      regarding the identification and qualification of ITX residue in milk migrated
      from food contact packaging materials was developed. The procedure was based on
      the gas chromatography-mass spectrometry (GC-MS) for screening and gas
      chromatography-tandem mass spectrometry (GC-MS/MS) for confirmation after a solid
      phase extraction (SPE) step using Florisil column with anthracene D10 (AD10) as
      the internal standard. Data was acquired in selective ion monitoring (SIM) mode
      with the following ions: m/z 184, m/z 224, m/z 239, m/z 254 for ITX and m/z 80,
      m/z 94, m/z 188, m/z 160 for AD10 in screening method of GC-MS. The m/z 254 was
      selected as the parent ion and m/z 239 as the daughter ion in the conformation
      method of GC-MS/MS. Data acquired employed the transition of m/z 254, m/z 239 for
      ITX and m/z 188, m/z 160 for AD10. The method gave limits of quantification (LOQ)
      of 7.0 microg/L (GC-MS) and 5.0 microg/L (GC-MS/MS) respectively as well as
      recoveries ranged from 74.9% to 89.6%. The analysis of real samples found two
      positives out of 11 different milk stuffs available using this method.

PMID- 17432574
TI  - [Headspace solid-phase microextraction-gas chromatography-mass spectrometry for
      analysis of volatile components from Atractlodes macrocephala Koidz].
AB  - Headspace solid-phase microextraction (HS-SPME) technique was employed to extract
      the volatile components from Chinese traditional medicine, Atractlodes
      macrocephala Koidz. The volatile components were isolated and identified
      successfully by gas chromatography-mass spectrometry (GC-MS). The results from HS
      SPME-GC-MS were compared with those obtained from steam distillation-GC-MS (SD-GC
      MS) with a good agreement. The volatiles were collected using a
      polydimethylsiloxane-divinylbenzene (PDMS-DVB) fiber by HS-SPME. The best
      response was obtained when the extraction temperature was 70 degrees C, the
      equilibrium time and extraction time were all 30 min and the desorption time was
      4 min. Analysis was performed by GC-MS with a polysiloxane capillary column (30 m
      x 0.25 mm, film thickness 0.25 microm) using He as the carrier gas and a
      programmed temperature run. Forty-one components accounting for 90.81% were
      identified. The main components (relative amount more than 1%) of the samples by
      HS-SPME were atractylone (40.12%), gamma-elemene (14.73%), aromadendrene
      (13.05%), eudesma-4 (14), 11-diene (5.46%), caryophyllene (2.56%), patchoulene
      (2.55%), 6,10,11,11-tetramethyl-tricyclo [6.3.0.1(2,3)] undec-7-ene (2.11%),
      cedrene (1.48%), alpha-caryophyllene (1.48%) and selina-4 (14) -7 (11) diene-8
      one (1.01%). By SD-GC-MS, 31 components accounting for 88.19% were identified and
      all these components could be extracted by SPME except trans-beta-ocimene which
      accounts only 0.10%. The results showed that the HS-SPME technique can be used to
      extract the the volatile components from Atractlodes macrocephala Koidz. in place
      of the traditional time-consuming SD.

PMID- 17432575
TI  - [Determination of trace phenol compounds using gas chromatography-mass
      spectrometry coupled with Tenax adsorption tube for enrichment of air samples].
AB  - A novel determination method for trace of seven phenol compounds in air samples
      has been established. They were collected with Tenax adsorption tube (180 mm x 60
      mm glass tube packed with 150 mg Tenax (40 - 60 mesh)) and desorbed with
      methanol. Five microlitres of naphthalene-D8 (internal standard) solution was
      added to the eluate. One microlitre of the mixture solution was injected into an
      HP-5MS capillary column (30 m x 0.25 mm x 0.25 microm) and determined by gas
      chromatography-mass spectrometry with selected ion monitoring (GC-MS/SIM). The
      selected ions were m/z 94, 95, 66, 108, 107, 77, 90, 122, 121, 107 and 136. The
      quantitative ions, m/z 94 for phenol, m/z 108 for cresol, m/z 122 for xylenol and
      m/z 136 for internal standard, were selected. The average recoveries of phenol
      compounds (spiked at the levels of 0.25, 1.00, 5.00 microg) ranged from 92.4% to
      102% and the relative standard deviations were less than 4.8%. When the air
      sample volume was 10 L, the detection limits were less than 0.001 mg/m3. Good
      linearities were observed in the range from 0.05 to 20.0 mg/L. The method is
      simple, fast, sensitive and accurate for the determination of phenol compounds in
      air samples.

PMID- 17432576
TI  - [Extraction and determination of essential oils in Indocalamus latifolius leaves
      and Indocalamus tessellatus leaves].
AB  - Indocalamus leaves are the generic name of the leaves of Indocalamus (Graminales)
      plants. The essential oils in Indocalamus latifolius leaves and Indocalamus
      tessellatus leaves were extracted by steam distillation method. Ether was used as
      the solvent to extract volatile compounds many times. Both the volatile compounds
      in Indocalamus latifolius leaves and Indocalamus tessellatus leaves were analyzed
      by gas chromatography-mass spectrometry (GC-MS). The results showed that thirty
      seven compounds were identified for the essential oils extracted from Indocalamus
      latifolius leaves, and its main components were found to be 3-hexen-1-ol, (Z)-; 1
      hexanol; benzyl alcohol; hexanal; furan, 2-ethyl-; 3-buten-2-one, 4-(2,6, 6
      trimethyl-1-cyclohexen-1-yl), (E)-; etc. Forty-nine components were identified
      for the essential oils extracted from Indocalamus tessellatus leaves, and its
      main components were found to be 3-hexen-1-ol, (Z)-; benzyl alcohol; 3-buten-2
      one, 4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (E)-; 2-hexenal; phenylethyl
      alcohol, 2-methoxy-4-vinylphenol; furan, 2-ethyl-; etc. 3-Hexen-1-ol, (Z)- was
      the most abundant compound in the essential oils from both Indocalamus leaves.
      There were ketone, aldehyde, alcohol, phenol and ester in them. The contents of
      ketones, aldehydes, and alcohols were found higher than those of other compounds
      in the two essential oils.

PMID- 17432577
TI  - [Purification and identification of a novel ACE inhibitory peptide derived from
      the mud snail Bellamya purificata by RP-HPLC/MALDI-TOF MS].
AB  - Bellamya purificata is one of mud snails in fresh water found in China. The
      purification and identification of an angiotensin I-converting enzyme (ACE)
      inhibitory peptide extracted from Bellamya purificata hydrolysate are described.
      The peptide was purified twice with semi-preparative reversed-phase high
      performance liquid chromatography (RP-HPLC) to obtain an active fraction with an
      inhibitory concentration 50% (IC50) of 43.5 micromol/L. The primary structure of
      the purified peptide was identified by the high performance liquid
      chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) and the
      martix-assisted laser desorption/ionization time of flight mass spectrometry
      (MALDI-TOF MS) combining with the amino acid composition analysis. Finally, it
      was identified as a tetrapeptide and sequenced as Lys-Glu-Ile-Trp (KEIW), which
      has the common characters of ACE inhibitory peptide extracted from selfish
      muscle. The structure identification results from the two methods were also
      compared in this study. The results from ESI-MS included a lot of information,
      such as the total ion current chromatogram and ultraviolet scan spectrum.
      However, the exact structure could only be from the MALDI-TOF MS analysis, in
      which the exact MS/MS spectrum could be obtained. Furthermore, the m/z
      measurement precision of MALDI-TOF MS was 0.0001 and much better than that of 0.1
      of ESI-MS.

PMID- 17432578
TI  - [Simultaneous determination of residues of malachite green, crystal violet and
      their leuco metabolites in aquatic products by liquid chromatography-tandem mass
      spectrometry].
AB  - A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed
      for the simultaneous determination of the residues of malachite green (MG),
      eucomalachite green (LMG), crystal violet (CV) and leucocrystal violet (LCV) in
      aquatic products. The target analytes were extracted from homogenized samples
      with a mixture of acetonitrile and ammonium acetate buffer, partitioned against
      methylene chloride, and purified on tandem neutral alumina and PRS solid-phase
      extraction (SPE) cartridges. Chromatographic separation was achieved by using a
      ZORBAX SB-C18 column with an isocratic mobile phase consisting of ammonium
      acetate (0.5 mmol/L) and acetonitrile (10: 90, v/v) without on-line post-column
      oxidation with PbO2 which had been widely used in the previous methods.
      Identification and quantification were performed using multiple reaction
      monitoring (MRM) with one precursor ion, and two product ions for each analyte
      and electrospray ionization in positive mode. The limits of detection were 0.5
      ng/g. The recoveries were in the range of 77.6% - 98.1%, and the relative
      standard deviations were less than 8.2%. The results showed that the method is
      suitable for the determination of residues of MG, LMG, CV and LCV in aquatic
      products.

PMID- 17432579
TI  - [High speed separation and quantitation of Ralstonia solanacearum of different
      virulence using high performance ion exchange chromatography].
AB  - High performance ion exchange chromatography coupled with laser light scattering
      instrument was employed for the rapid separation and quantitation of Ralstonia
      solanacearum of different virulence. The pure culture of Ralstonia solanacearum
      was successfully separated into three characteristic fractions. Each fraction was
      collected and inoculated onto 2,3,5-triphenyltetrazolium chloride (TTC) plates to
      identify its virulence. The shapes and colors of the colonies were imaged, and
      the average attenuation index (attenuation index = red spot diameter of
      colony/total colony diameter) of ten colonies of each fraction was carefully
      determined. Furthermore, each fraction was inoculated into SPA liquid media at 30
      degrees C with shaking (200 r/min) for 48 h, the cells were harvested, suspended
      at a density of 1.2 x 10(9) cfu/mL, and applied to infect tomato tissue culture
      plantlets using leaf-cutting method. The infection mortality of the tomato tissue
      culture plantlets was recorded from 1 to 9 days after inoculation. The results
      showed that the virulences of each fraction were different on the basis of
      attenuation index and infection mortality. The virulence of peak 3 fraction was
      the strongest. On the contrary, the virulence of peak 1 fraction was the weakest.
      In addition, the linear relationships between different injection volumes (1 -
      180 microL) and their peak areas were investigated. The linearity was good within
      the range of the bacterial number of 9 x 10(6) - 9 x 10(8) (r = 0.99). This
      method can be potentially used as a novel tool for the rapid separation and
      quantitation of Ralstonia solanacearum of different virulences.

PMID- 17432580
TI  - [Analysis of monosaccharides and uronic acids in polysaccharides by pre-column
      derivatization with p-aminobenzoic acid and high performance liquid
      chromatography].
AB  - An ion-pair reversed-phase high performance liquid chromatographic (RP-HPLC)
      method for the simultaneous determination of carbohydrate and uronic acids was
      developed. p-Aminobenzoic acid (p-AMBA) was used for pre-column derivatization of
      the analytes, enabling fluorescence (lambda(ex) = 313 nm, lambda(em) = 358 nm) or
      ultraviolet (UV at 303 nm) detection. Reaction conditions such as reaction
      temperature and reaction time were optimized. Atlantis dC18 column with
      hydrophilic end capping was selected for the separation of derivatives. Effects
      of mobile phase compositions such as ion pairs and their concentrations and pH on
      the retention behaviors and separation results of 9 monosaccharides and 2 uronic
      acids were investigated. Derivatives of fructose, galactose, glucose, mannose,
      xylose, arabinose, ribose, galacturonic acid, fucose, glucuronic acid and
      rhamnose were separated within 42 min, applying tetrabutyl ammonium hydrogen
      bisulfate (TBAHSO4) as the ion pair reagent. The detection limits were between
      3.38 x 10(-8) mol/L and 176 x 10(-8) mol/L for fluorescence detection and between
      2.55 x 10(-7) mol/L and 13.4 x 10(-7) mol/L for UV detection. Good linearities
      were obtained with correlation coefficients (r2) above 0.99. The relative
      standard deviations (RSDs) of the peak area of the derivatives in 12 - 51 h after
      derivatization were from 2.5% to 3.9%. This method has been applied for the
      determination of mono-/disaccharides and uronic acids in spirulina polysaccharide
      after dissolved in trifluoroacetic acid solution (2 mol/L). The results showed
      this method is suitable for the analysis of monosaccharide compositions in
      polysaccharides.

PMID- 17432581
TI  - [Simultaneous analysis of six effective components in the anti-Alzheimer's
      disease effective component group of Xiao-Xu-Ming Decoction].
AB  - A method based on high performance liquid chromatography (HPLC) was developed for
      the quantitative determination of six components in an anti-Alzheimer medicine,
      Xiao-Xu-Ming Decoction, which is an effective prescription in treating stroke and
      the sequela of stroke by herbalist doctors for thousands years. The effective
      component group (ECG) was made according to the results of high-throughput
      screening, and the curative effect of ECG was validated on aging rats. In this
      method an ODS column was used. The mobile phase consisted of water-formic acid
      ethylenediamine (A; 100: 0.1: 0.1, v/v) and methanol-formic acid (B; 100 : 0.05,
      v/v), eluted with gradient (0 - 5 min, 20% B; 5 - 100 min, 20% B - 40% B; 100 -
      140 min, 40% B - 70% B). The flow rate was 1 mL/min. The detection wavelength was
      set at 240 nm. Under the above separation conditions, six components belonged to
      two different categories, indicans and alkaloids, were determined simultaneously.
      The relationships between the concentrations and the peak areas of these six
      components were all linear. The recoveries of the six components were 99.1% for
      paeoniflorin, 99.6% for prim-O-glucosylcimifugin, 98.4% for baicalin, 99.9% for
      4'-O-beta-D-glucosyl-5-O-methylvisamminol, 99.6% for fangchinoline, and 102.0%
      for tetrandrine. The relative standard deviations (RSD) were 1.3%, 1.4%, 0.4%,
      0.8%, 0.2%, and 1.4%, respectively. This method is simple and reproducible and it
      can be used for the quality control of the effective component group of Xiao-Xu
      Ming Decoction.

PMID- 17432582
TI  - [Simultaneous determination of polyacetylene components in Cangzhu by reversed
      phase high performance liquid chromatography].
AB  - In traditional Chinese medicines, atractylodes rhizome ("Cangzhu" in Chinese) is
      used for the treatment of rheumatic diseases, digestive disorders, mild diarrhea,
      night-blindness. According to the Pharmacopoeia of China (2005 Edition), Rhizoma
      Atractylodis is the dried root of Atractylodes lancea (Thunb.) DC. or
      Atractylodes chinensis (DC.) Koidz. Polyacetylenes is one group of the most
      important active components in Cangzhu. A reversed-phase high performance liquid
      chromatographic method was developed for the simultaneous determination of two
      main polyacetylene components including atractylodin and atractylodinol in
      Cangzhu. The chromatographic analysis was carried out using a Polaris-C18 column
      and the mobile phase of acetonitrile-water with the flow rate of 1.0 mL/min. The
      detection wavelength was set at 340 nm, and column temperature was set at 25
      degrees C. The detection limits (S/N = 3) were 0.069 and 0.016 microg for
      atractylodin and atractylodinol, respectively. The recoveries of the two
      polyacetylene components were found in the range of 97.4% - 104.6%. Thirteen
      samples collected were determined which includes three species of atractylodes
      rhizome, A. lancea, A. chinensis, and A. japonica. This rapid and accurate method
      has been successfully applied to the simultaneous determination of the two
      polyacetylene components in Cangzhu.

PMID- 17432583
TI  - [Isolation and preparation of flavonoids from the leaves of Nelumbo nucifera
      Gaertn by preparative reversed-phase high performance liquid chromatography].
AB  - It has been confirmed that flavonoids in the leaves of Nelumbo nucifera Gaertn
      (lotus leaves) have many pharmacological activities. Currently, total flavones in
      the leaves of Nelumbo nucifera Gaertn have been studied extensively, however,
      only a few researches were able to investigate the individual components in it.
      At first, crude extract was obtained from lotus leaves by reflux extraction using
      60% ethanol for three times. Then, the concentrated crude extract was separated
      on a D-101 column (eluted with 70% ethanol) and a polyamide column (step gradient
      15% to 90% ethanol). The Fr-1 fraction was obtained from the eluate of 45%
      ethanol and was subjected to a preparative reversed-phase high performance liquid
      chromatograph (RP-HPLC) for the isolation of target components. The preparation
      of the individual flavonoids was carried out on an RP-HPLC with a Symmetry Prep
      C18 column, and the mobile phase was water-acetonitrile at a flow rate of 5.0
      mL/min. Three compounds were identified with ultra violet absorbance (UV),
      infrared (IR), nuclear magnetic resonance (NMR) and mass spectrometry (MS). They
      were hyperin, isoquercetin and astragalin. To our knowledge that astragalin was
      the first time successfully isolated from this plant. The purity of the three
      compounds was all over 97%.

PMID- 17432584
TI  - [Application of fingerprint chromatogram in quality assessment of apple cider].
AB  - Fingerprints of 14 apple cider samples from different manufacturers were studied
      using high performance liquid chromatography (HPLC) with an electrochemical
      detector (ECD). The analysis was carried out on a Zorbax SB-C18 column at 30
      degrees C with 2% (v/v) methanol aqueous solution-4% (v/v) acetic acid aqueous
      solution as mobile phase at a flow rate of 0.8 mL/min. The electrochemical
      detector was set at 0.7 V. By calculating the relative retention times of certain
      peaks with chlorogenic acid as the reference standard, 8 common peaks in the
      samples were analyzed. Relative retention times for the common peaks of various
      samples were calculated, and the similarities of all the samples were figured out
      through each peak area with the vectorial angle cosine method and correlative
      coefficient method. The results indicated that apple cider products of the same
      manufacturer have good similarity, with the similarities greater than 92.7%.
      According to this experiment, effectual microcosmic information for apple cider
      analysis was gained through HPLC and ECD. Moreover, this test method will help
      the analysis and the control of product quality, the development of new products
      and the establishment of trade standard.

PMID- 17432585
TI  - [Study on capillary electrophoresis fingerprints of Flos Lonicerae Japonicae].
AB  - The capillary electrophoresis fingerprints (CEFP) of Flos Lonicerae Japonicae was
      established to control its quality. In the capillary zone electrophoresis (CZE)
      pattern 50 mmol/L sodium borate contained 20 mmol/L beta-cyclodextrin (beta-CD)
      adjusted to pH 8.0 with phosphoric acid was applied as the background
      electrolyte. The running voltage was 12 kV and the detection wavelength was 254
      nm. The Flos Lonicerae Japonicae was extracted by water and the sample solution
      was injected into the capillary by hydraulic pressure in 15 s. The 18 common
      peaks were marked according to the emerging rate of 100% and by comparing each
      fingerprint with the other one among the 13 samples cultivated in different
      places, in which chlorogenic acid was selected as the reference peak. The CEFP
      had good precision and reproducibility with the relative standard deviations
      (RSDs) of the relative migration times less than 3% and the RSDs of the relative
      peak areas within 6.1%. The novel concepts of the apparent quantitative
      similarity (R), the quantitative similarity calculated by vector projection (C)
      and the quantitative similarity (P) were introduced firstly. The good crude drugs
      should posses two merits as follows: the qualitative similarity (S) which
      displays the distribution of the chemical constituents in sample should be more
      than 0.90; the quantitative similarities (R, C, P, Q) that disclose the overall
      contents of the chemical constituents in sample should be within 80% - 120%. This
      method was applied in the quality control practice, and the results showed that
      the method could be used for the overall quality control of Flos Lonicerae
      Japonicae and is especially suitable for qualitative and quantitative evaluation
      of chromatographic fingerprints both in chemical constituent distribution and in
      contents.

PMID- 17432586
TI  - [Separation of phosphodiester oligodeoxynucleotides and phosphorothioate
      antisense oligodeoxynucleotides by capillary zone electrophoresis at low pH].
AB  - Oligodeoxynucleotides (ODNs) may possess biological activity in vivo, and are
      used for the cancer therapeusis. Synthesized ODNs contains many by-products, and
      so their purity check and resolution of single-base, i. e., the separation of
      ODNs differing by one nucleotide in length, become necessary. In this study,
      capillary zone electrophoresis (CZE) method was developed for the separation of
      two sets of model compounds of single-stranded oligodeoxynucleotide mixtures (18 
      20 mers), phosphodiester oligodeoxynucleotides (PO-ODNs) and their
      phosphorothioate modifications (PS-ODNs), with equal sequences differing in a
      single base. The effects of the CZE operating parameters on the separation were
      investigated and optimized to further improve the resolution, such as the pH
      values and the concentrations of running buffer, the varieties and concentrations
      of additives, the separation voltage as well as the temperature. It was confirmed
      that the pH value of the buffer played the most important role in the separation,
      and the urea used as the additive in the system improved significantly the
      resolution of PS-ODNs. Consequently, the PO-ODNs and PS-ODNs mixtures could be
      single-based separated on a fused-silica capillary of 50 microm x 49.0 cm (40.7
      cm of effective length) under the optimum conditions: the running buffer system
      of 50 mmol/L NaH2PO4-H3PO4 (pH 2.24)-7 mol/L urea, the pressure injection of 2
      kPa x 10 s, the separation voltage of -20 kV, the column temperature of 25
      degrees C, and the ultraviolet (UV) detection at 260 nm. The average resolutions
      for the separation of 18 - 19 mers and 19 - 20 mers of PO-ODNs were 4.68 and
      3.20, respectively; and the average resolutions for the separation of 18 - 19
      mers and 19 - 20 mers of PS-ODNs were 1.23 and 0.81, respectively. The relative
      standard deviations of the migration time and the resolution were all less than
      5%. This method will be useful for the qualification of PO-ODNs and PS-ODNs
      samples as they are used in antisense drug development due to the relatively easy
      operation and good reproducibility of the method in comparing with the capillary
      gel electrophoresis.

PMID- 17432587
TI  - [Simultaneous determination of twenty-one organic acids in food by ion
      chromatography with eluent autogeneration].
AB  - A novel ion chromatographic method was developed for the simultaneous
      determination of organic acids in food samples including quinic acid, acetic
      acid, pyruvic acid, ketosuccinic acid, mannitic acid, lactic acid, succinic acid,
      malic acid, tartaric acid, oxalic acid, fumaric acid, ascorbic acid, alpha
      ketoglutaric acid, cinnamic acid, salicylic acid, citric acid, isocitric acid,
      ferulic acid, cis-aconitic acid, trans-aconitic acid, beta-coumaric acid. 5 - 34
      mmol/L KOH produced by an EG40 eluent autogenerator could achieve a flat baseline
      and lower background conductance when performing gradient elution. The flow rate
      was 0.6 - 2.5 mL/min and the injection volume was 25 microL. The separation was
      performed on an IonPac AS11 column and detected by suppressed conductivity with
      self-regenerating suppressor mode. The samples were prepared through extraction,
      decoloration and filtration before analysis. Twenty-one organic acids showed good
      linear relationship between the mass concentration and the peak area in the
      measurement ranges. The correlation coefficients were above 0.999 and the
      detection limits were 0.011 - 0.188 mg/L, and the average recoveries were 91.5% -
      101.8%. The method is simple and rapid with good accuracy and reproducibility,
      and has been applied to determine twenty-one organic acids in diversiform samples
      with satisfactory results.

PMID- 17432588
TI  - [Simultaneous determination of polychlorinated biphenyls and DDT in biological
      tissues using GC-MS/MS].

PMID- 17432590
TI  - [Determination of perfluorooctanoic acid and its salts in packaging materials
      using LC-MS/MS method].

PMID- 17432589
TI  - [Determination of verapamil in human plasma by LC-MS/MS].

PMID- 17432591
TI  - [Determination of alpha-lactalbumin and beta-lactoglobulin in whey protein by RP
      HPLC].

PMID- 17432592
TI  - [Research on the aging rule of the writings with copying paper by high
      performance liquid chromatography].

PMID- 17432593
TI  - [Determination of trace nitrites and nitrates in seawater by ion chromatography
      coupled with silver oxide precipitation].

PMID- 17432594
TI  - [Structural-functional organization of the adenylyl cyclases in unicellular
      eukaryotes and molecular mechanisms of its regulation].
AB  - At the present time, adenylyl cyclases (ACs)--the enzymes, catalyzing the
      formation of second messenger cAMP, were found in yeasts and related fungi,
      amoeba Dictyostelium discoideum, flagellates, malaria plasmodium, ciliates.
      However, structural-functional organization of the ACs and molecular mechanisms
      of its regulation are different to great extent. The scores of structurally
      related ACs, one time penetrating the membrane and possessing the receptor
      function, were identified in flagellates. Three types of ACs, strongly differed
      in the topology, the domain organization and the sensitivity to regulatory
      molecules and physical factors, were found in amoeba D. discoideum. One of them
      (AC-A) is close to membrane-bound ACs of the mammals and can be regulated by
      extracellular cAMP. It was shown that the enzymes of the yeasts, lacking the
      transmembrane domains, formed the intermolecular complexes, which were stabilized
      by the interactions between leucine-rich repeat regions. The data presented in
      the review give evidence that the main molecular mechanisms of the functioning of
      vertebrate ACs were formed in unicellular organisms and fungi. At the same time
      the structure and functions of the ACs of the lower eukaryotes are strongly
      varied. It can be connected with the special features of life cycle of the lower
      eukaryotes and with the realization of different models of functioning and
      regulation of cAMP-dependent cascades at the earlier steps of evolution.

PMID- 17432595
TI  - [Confocal-microscopic study of skeletal muscle fibre membrane organelles during
      Zenker's (spreading) necrosis].
AB  - The changes of T-system and cellular acidic organelles during spreading
      (Zenker's) necrosis of frog skeletal muscle fibres have been investigated using
      laser confocal microscopy and several vital fluorescent dyes acridine orange, RH
      414, DiOC6(3), rhodamine 123, fluorescein dextran. The formation of numerous
      vacuoles as a result of local T-system swelling is most characteristic for
      initial steps of Zenker's necrosis. Vacuoles can attain tens microns in length.
      They are located both near nuclear poles and between myofibres. Vacuoles maintain
      connections with the extracellular space up to the moment of contraction knot
      rejection, and under definite conditions (glycerol influx to fibre) vacuoles are
      reversible. They deform nuclei and sarcoplasmic reticulum cisternae. Cellular
      acidic organelles, accumulating acridine orange (lysosomes, late endosomes, Golgi
      apparatus cisternae) are situated in direct vicinity with normal and vacuolated T
      system. The increase in acidic organelles number and size occur during the
      pathological process development, and tendency to vacuoles clusterization may be
      seen. Vacuolation of T-system during necrosis is not followed by vacuole content
      acidification. The role of cellular acidic organelles and of T-system vacuolation
      in the development of different muscle pathological changes is discussed.

PMID- 17432596
TI  - [Role of p38alpha kinase in activation of premature senescence program in
      transformed mouse fibroblasts].
AB  - We investigated the role of p38alpha stress-kinase in regulation of premature
      senescence program, stimulated by histone deacetylase inhibitor--sodium butyrate
      (NaB)--after application to rodent transformed cell lines. Investigation was
      performed on the E1A + cHa-ras transformants selected from mice embryonic
      fibroblasts null at the p38alpha kinase gene or null fibroblasts at the PPM1D
      gene, which encoded phosphatase Wip1. Absence of Wip1 led to constitutive
      activation of p38alpha kinase. It was revealed that after NaB treatment both cell
      lines completely stopped proliferation due to irreversible cell cycle arrest in
      G1/S phase. In both cell lines sodium butyrate induced sustained block of
      prolifaration due to irreversible cell cycle arrest in G1/S phase. Following
      sodium butyrate treatment cells expressed marker of senescence--beta
      galactosidase activity (SA-beta-Gal). Long-term (during several days) NaB
      treatment of cells led to partial restoration of actin cytoskeleton, focal
      adhesion contacts and heterochromatin focus formation (SAHF) in the nucleus of
      senescent cells. Obtained data allow us to suppose that irreversible process of
      cellular senescence activated by sodium butyrate can occur in the absence of
      functionally active p38 kinase by means of other ways of cell cycle suppression.

PMID- 17432597
TI  - [Hepatocyte mitochondrion respiratory chain in rats with experimental toxic
      hepatitis].
AB  - The purpose of this study was to examine hepatocyte mitochondrion respiratory
      chain in rats subjected to ethanol and CCl4 administration within 4 weeks to
      induce an experimental hepatitis. Oxygen consumption was determined as a measure
      of mitochondrion respiration chain function. The development of liver pathology
      was accompanied by fat accumulation, fibrosis, triglycerides and lipid
      peroxidation increase. Respiratory chain characteristics damage was found.
      Endogenous oxygen consumption by hepatocytes isolated from pathological liver was
      found 34% higher compared to control. Exogenous malate and pyruvate substrates
      delivery didn't stimulate cell respiration. Rotenone (the inhibitor of the I
      complex) decreased 27% oxygen consumption by pathological hepatocytes while
      dinitrophenol produced 37% cell respiration increase. States 3 (V3) and 4 (V4)
      mitochondrial respiration with malate + glutamate as substrates were found to be
      70 and 56% higher accordingly compared to control level. V3 and Vd (dinitrophenol
      respiration) for mitochondria from pathological liver didn't differ from control
      when being tested with malate + glutamate or succinate as substrates. Cytochrome
      c oxidase activity increased (+ 80%) as compared to control. Administration of
      hypolipidemic agent simvastatin simultaneously with ethanol and CC14 resulted in
      decrease liver fat accumulation, fibrosis and peroxidation products. Simvastatin
      administration caused hepatocyte endogenous respiration decrease while malate +
      pyruvate, dinitrophenol or rotenone delivery produced oxygen consumption
      alterations similar to control. However, when isolated mitochondria from liver of
      simvastatin treated animals being tested the decrease of oxidative
      phosphorylation coupling for substrates malate + glutamate was found. While
      simvastatin did not cause changes in cytochrome c oxidase activity. We propose
      the hypothesis that the NCCR complex in rat mitochondria with experimental toxic
      hepatitis works extensively on superoxydanion production. Alterations of SCCR,
      Coenzyme Q-cytochrome c-reductase, cytochrome c oxidase and ATP-synthase
      activities have an adaptive nature to compensate for impaired NCCR function.

PMID- 17432598
TI  - [Cell sources of liver development].
AB  - The work is devoted to consequent expression of different cell types' protein
      markers such as vimentin, desmin, cytokeratins 7, 18, 19, stem cell markers CD34
      and Bcl-2 at early stages of human prenatal development. Desmin was revealed in
      sinusoidal liver cells on 3.5-12 weeks of gestation, in mesenchymal cells of
      ventral mesentery and hepatoblasts on the 4-7 accordingly. During hepatic period
      of blood formation such desmin positive sinusoidal cells were found to be located
      close to blood cells. So called "cholangio-" cytokeratins 7 and 19 showed
      different expression, the first one was found only in cholangiocytes, while
      cytokeratin 19 existed in hepatoblasts as well until week 15-16 of prenatal
      development. Mesenchymal cells of ventral mesentery are positive for cytokeratins
      18 and 19 even brighter than hepatoblasts in the 4-7 weeks of gestation. Bcl-2
      expression was seen in the same periods in most sinusoidal and mesenchymal cells
      of ventral mesentery. CD34 positive cells are strongly depicted in liver
      sinusoids from 4th until 9th weeks of gestation, but probably they are not a
      source of hepatocytes' development in embryonic ontogenesis. Ventral mesentery
      mesenchyme was negative for this very marker. These results let us suppose that
      hepatocytes and cholangiocytes may develop from quite different embryonic
      sources: cholangyocytes grow exceptionally from duodenum epithelial cells, while
      there is a strong possibility that hepatoblasts formation occurs with
      participation of mesenchymal cells.

PMID- 17432600
TI  - [Decompactization of chromosome 1 in the artificially decondensed human sperm
      nuclei: overall topology and non-random location of chromosome bends].
AB  - We have used FISH with microdissected chromosome arm-specific DNA probes that
      allow direct visualization of chromosome 1 folding in human sperm nuclei. We
      described the overall topology and the mode of packaging of sperm chromosome 1
      and thus established new elements of ordered genome architecture in these
      specialized cells.

PMID- 17432599
TI  - [Regulation of the 26S proteasomes' endoribonuclease activity specificity in k562
      cells under effect of differentiation and apoptosis inductors].
AB  - The specificity of 26S proteasomes' endoribonuclease activity has been shown to
      be changed under effect of erythroid differentiation (hemin) and programmed cell
      death (diethylmaleate) inductors in proerythroleukemic K562 cells. Treatment of
      K562 cells with apoptosis and differentiation inductors leads to the specific
      stimulation of RNase activity towards certain mRNA and to reduction of proteasome
      RNase activity towards other mRNA. The enzymatic activity under study has been
      demonstrated to be specifically and selectively dependent on phosphorylation of
      26S proteasome subunits as well as on Mg and Ca ions. The conclusion is drawn
      that the specificity of the proteasomes' RNAse activity is regulated during
      differentiation and apoptosis, and selective regulation of the activity of
      different nuclease centers is suggested, the mechanism involving changes in
      phosphorylation of proteasome subunits and cation homeostasis.

PMID- 17432601
TI  - [The influence of the EGF on proliferative signal transduction in ciliate
      Tetrahymena pyriformis].
AB  - It has been shown that the transduction of the proliferative signal induced by
      EGF in ciliata Tetrahymena pyriformis cells is not connected with
      autophosphorylation of the receptor tyrosine kinases. The results obtained
      indicate that EGF in ciliata cells initiates the mitogenic pathway including the
      membrane proteins of the tyrosine kinases-like type (without tyrosine
      phosphorylation sites), adenylate cyclase, tyrosine- and Ca2+ -dependent ERK-like
      kinases.

PMID- 17432602
TI  - [Cajal bodies in insect oocytes. II. New data on the molecular composition of
      cajal bodies in oocytes of the house cricket Acheta domesticus with special
      reference to interactions between cajal bodies and interchromatin granule
      clusters].
AB  - Cajal bodies (CBs) in oocytes of the house cricket Acheta domesticus are large,
      perfectly spherical nuclear organelles with a complex internal structure. These
      consist of a fibrillar coilin-containing matrix and a central cavity with a
      prominent fibrogranular body inside; the latter has been referred to as an
      "internal" interchromatin granule cluster (IGC). Within the matrix of CBs we
      detected transcriptional co-activators CBP/p300 and TATA-box binding protein
      (TBP). No RNA polymerase II was revealed in CBs of both normal and actynomycin D
      treated oocytes. In the nucleoplasm of A. domesticus oocytes, besides CBs, free
      IGCs were observed. In oocytes treated with actynomycin D, the amount of "free"
      IGCs in the nucleoplasm increase significantly, granular and fibrillar components
      of IGCs were seen segregated, and RNA polymerase II and CBP/p300 were found to be
      accumulated in fibrillar zones of IGCs.

PMID- 17432603
TI  - [Quantity of functionally changed cells as an identificator of the moment of the
      organizmus transfer to the next period of development].
AB  - As "the threshold gears are peculiar to all processes which are flowing past in
      the world", the problem of looking up of quantitative criterion determining
      transition of a biological system from one condition to another, is one of the
      main problems of natural sciences. For analysis of the given problem we
      investigated some stages of forwardness of marine aster Asterias rubens (mean and
      late blastula, early and late gastrula, early larva), dis- tinguishing among
      themselves by morphological characters. Change of structure of cell populations
      at each stage of development A. rubens analyzed with the help of method of
      quantitative assessment of functional condition of cells genome. The method is
      based on cytophotometryc analysis of cell populations coloured by Feulgen
      (quantifying of DNA in cell) and Naftol yellow S (quantifying of histones in a
      cell). As the criterion of estimation of functional condition of the cell was
      used the parameter CFAGEN, coefficient of functional activity of cell genome
      deduced from histone/DNA ratio after estimation of the absorbency of the nucleus
      coloured by two chromophores. The data obtained showed that at the moment of
      organism transition from one stage of development (late blastula) to another
      (early gastrula) the difference in CFAGEN values between these stages was
      statistically authentic. Thus comparison of cell distribution histograms has show
      that cell population conforming to the early gastrula contains 33 % cells with
      the level of genome functional activity that differs from this one in the cell
      population conforming to the late blastula. Just in the same moment, the
      transition of an organism from the stage of late gastrula to the stage of larva
      is accompanied by statistically authentic distinction in CFAGEN between these
      stages and availability of more than 1/3 cells (34 %) of the population at the
      larva stage showing genome functional activity different from that at the late
      gastrula stage. Thus, it is established, that the biological system passes to
      qualitatively new condition, if quantity of members of this system changes
      (increaser or decreases comparatively to a standard point of reference: the norm,
      previous system status and etc.) not less than on 1/3.

PMID- 17432604
TI  - [Modulation of programmed death of the peripheral blood lymphocytes under chronic
      virus infection].
AB  - We investigated programmed death of lymphocytes in patients with chronic
      infections--tick-borne encephalitis, hepatitis B and C. It has been shown that
      the character of disorders in realization of lymphocyte apoptosis depends on
      molecular features of the infectious agent. Apoptotic death of lymphocytes was
      elevated after incubation in vitro with dexamethazone, etopozide and in medium
      without serum. Receptor-dependent and mitochondrial paths of apoptotic signal
      conduction are preferentially modulated under chronic virus persistence.

PMID- 17432605
TI  - [Cultured skin cells interaction with polylactide surface coated by different
      collagen structures].
AB  - The purpose of this work was an optimization of polylactide film surfaces
      designed for human keratinocytes cultivation. The polylactide films were coated
      by collagen 1. The experiments showed that uniform covering of polymer surface by
      collagen, and formation of different collagen structures depend on the mode of
      the protein application. The differences in collagen distribution on the polymer
      surface influened the keratinocytes growth in culture. Analysis of keratinocytes
      alignment, as well as cytoskeleton organization demonstrated that fibrillar
      collagen promoted more even keratinocytes distribution in comparison with the
      distribution on molecular collagen.

PMID- 17432606
TI  - [Heterogeneity of stromal precursor cells isolated from rat bone marrow].
AB  - Bone marrow stroma contains mesenchymal stem cells (MSC) which are precursor for
      at least mesenchyma-derived cells. Recent investigations revealed a lot of
      questions concerning MSC biology that should be further refined. The aim of this
      study was the comparative analysis of rat bone marrow stroma cells cultures.
      Mesenchymal precursor cells isolated from rat bone marrow were passed up to 50
      times. Comparative morphological and immunophenotypical analysis of these
      cultures was carried out as well as their ability to osteogenic differentiation
      was studied. The isolated cultures contained morphologically different types of
      cells and thus showed a high heterogenity level. Morphology of these cell types
      was described. The heterogeneity level was reported to decrease over time. It was
      found out that subcultures isolated from different rats shared the same
      immunophenotype characteristics (CD90+, CD44+, CD54+, CD 106+, CD45-, CD11b-),
      but differed in their morphology as well as in ability to osteogenic
      differentiation. Thus MSC identification requires more specific marker and
      functional tests to be used.

PMID- 17432607
TI  - [Localization of NADPH-diaphorase and choline acetyltransferase in the central
      nervous system of the bivalve mollusk Mactra sulcatoria].
AB  - The presence of NADPH-diaphorase and choline acetyltransferase (ChAT) in all
      ganglia of the Mactra sulcatoria was demonstrated by histochemical and electron
      histochemical methods. Pecularities of cholinergic and nitrergic neurons
      localization were revealed in nervous ganglia, and their relative content there
      was estimated. It was established that in reaction to ChAT only large neurons
      were marked. Ultrastructural localization of NADPH-diaphorase and ChAT was
      determined in neurons and neuropile. The data obtained testify that NADPH
      diaphorase and ChAT are located in different types of nervous cells. The
      opportunity of functional cooperation in activity of cholinergic and nitrergic
      systems in mollusks is discussed.

PMID- 17432608
TI  - [Discrimination of heterozygote currency of ataxia-telangiectasia by indirect
      immunofluorescent analysis].
AB  - The qualitative differences in P53 protein stabilization after ionizing
      irradiation in different doses were found in cells of members of ataxia
      telangiectasia (AT) family--proband AT6SP, her sister AT(S)6SP and father
      AT(F)6SP. The method of indirect immunofluorescence with confocal microscopy was
      used.

PMID- 17432609
TI  - [DNA of some regions of constitutive heterochromatin is demethylated and
      decondensed in MRC5 and A431 cells].
AB  - It is believed that satellite DNA is compact and transcriptionally inert during
      interphase. We determined localization, range of compactization and methylation
      state of the centromeric and pericentromeric satellite DNA using the method of
      fluorescence hybridization in situ (FISH) combined with the antibody
      immunostaining against the methylated DNA. We investigated the tissue cells (the
      cells of placenta and lymphocytes), primary (MRC5 fibroblasts) and malignant
      (A431) cell cultures. Centromeric satellite DNA was condensed and stained with
      antibodies against 5-methylcytosine in all the cases. Pericentromeric satellite 3
      of the chromosome 1 was condensed in lymphocytes, placenta cells and young
      culture of fibroblasts. The unwrapping of satellite 3 of the chromosome 1 has
      been observed in the senescent MRC5 fibroblasts and in the malignant cell line
      A431. The compact areas of pericentromeric satellites were stained with
      antibodies against the methylated DNA, white the decondensed areas were'nt
      stained. Thus, we observed pericentromeric satellite 3 decondensation in
      senescent fibroblasts culture MRC5 and in cell line A431. The decondensation was
      accompanied by the partial demethylation of the satellite DNA, which is believed
      to belong to constitutive heterochromatin.

PMID- 17432611
TI  - [Ca-dependent modulation of human glycine receptors expressed in cultured cell
      lines].
AB  - Glycine receptors (GlyRs) provide the main inhibitory neurotransmission in spinal
      cord and brainstem synapses of vertebrates. Fucile et al. (2000) discovered that
      elevation of intracellular Ca2+ caused rapid potentiation of GlyRs. This
      modulation develops in less than 100 ms. It is characterized by an increase in
      GlyR apparent affinity for glycine. It has been suggested that the phenomenon of
      Ca-induced potentiation involves an unknown Ca2+-binding protein (CaBP). Using
      the yeast two-hybrid system, screening of human brain cDNA library against the
      cytoplasmic loop of human alpha 1 subunit (GlyRhl) allowed us to identify five
      new interactors. One of them belongs to a family of Ca-binding proteins. We
      analyzed effect of "short" forms of this protein (CaBP-S) on functional
      properties of GlyRhl expressed in HEK-293 and CHO cells. Using whole-cell
      recordings and rapid agonist application we constructed concentration
      dependencies of glycine-induced currents. This analysis revealed statistical
      differences in EC50s between control cells (expressing only GlyRhl) and those
      expressing CaBP-S. In HEK-293 cells recorded under conditions of low
      intracellular Ca concentration (BAPTA 20 mM in the recording pipette), EC50 for
      glycine in control cells and expressing GlyRhl + CaBP-S were, correspondently,
      68+/-49 microM (n = 29) and 409 +/-421 microM (n = 60). In CHO cells EC50 were
      54+/-43 microM (n = 25) and 123 +/-104 microM (n = 28). These differences were
      statistically not significant at recording with intracellular solution containing
      high Ca concentration (50 microM). In this case EC50 were correspondently 35+/-28
      microM (n = 7) and 64 +/-38 microM (n = 7). These results suggest that CaBP-S
      causes decrease of GlyR sensitivity to agonist through interaction with
      cytoplasmic domain of GlyR.

PMID- 17432610
TI  - [Prooxidant and cytotoxic action of N-acetylcysteine and glutathione combined
      with vitamin Bl2b].
AB  - We studied the prooxidant and cytotoxic action of thiols N-acetylcystein (NAC)
      and glutathione (GSH) combined with vitamin Bl2b. The synergism of action of the
      thiols and Bl2b resulted in human carcinoma cell damage was found. It was shown
      that GSH and NAC in physiological doses combined with Bl2b caused the initiation
      of apoptosis. It was established that prooxidant action of the thiols combined
      with vitamin Bl2b, i. e. generation and accumulation of hydrogen peroxide in
      culture medium, led to intracellular oxidative stress and injury of cell redox
      system. These effects were completely abolished by nonthiol antioxidants catalase
      and pyruvate. The chelators of iron phenanthroline and deferoxamine did not
      suppress the H2O2 accumulation in culture medium but significantly inhibited the
      cell death induced by the thiols combined with Bl2b. Therefore, the thiols GSH
      and NAC widely used as antioxidants, in combination with vitamin Bl2b show
      prooxidant characteristics and induce, with the participation of intracellular
      iron, apoptotic HEp-2 cell death.

PMID- 17432612
TI  - [Prognosis of yeast cells recovery after simultaneous exposure to UV-radiation
      and hyperthermia].
AB  - The results of experimental investigations of survival of diploid yeast cells
      Saccharomyces cerevisiae (strain XS800) after simultaneous exposure to UV
      radiation (254 nm) and hyperthermia (53-57 degrees C) have been described. It was
      shown that the portion of cells capable of recovery in innutrient medium after
      the action of these agents decreased with the increasing of temperature under
      which the irradiation was occurred. Mathematical model taking into account the
      synergistic interaction was suggested for quantitative prediction of irreversible
      component after combined actions of these agents. A good correspondence between
      experimental data and model predictions has been demonstrated. The importance of
      the results obtained for the interpretation of the synergistic interaction
      mechanisms are discussed.

PMID- 17432613
TI  - [History of the Chair of Parasitology, Faculty of Veterinary Medicine, Warsaw
      Agricultural University up to 1991].

PMID- 17432614
TI  - [History of the Department and Division of Parasitology Faculty of Veterinary
      Medicine Warsaw Agricultural University in 1992-2006].

PMID- 17432615
TI  - [Prof. dr Witold Jakub Stefanski, eminent scientist and preceptor, long-standing
      chief of Chair of Parasitology--Faculty of Veterinary Medicine, creator of the
      Polish Veterinarian Parasitology School].

PMID- 17432616
TI  - [Molecular diagnostic of parasites using rRNA gene sequence].
AB  - Ribosomal RNA (rRNA) is a component of the ribosomes. Eukaryotic ribosomes
      contain four different rRNA molecules: 18S, 5,8S, 28S and 5S rRNA. rRNA is the
      most conserved (least variable) gene in all cells. For this reason, genes that
      encode the rRNA (rDNA) are sequenced to identify an organism's taxonomic group,
      calculate related groups, and estimate rates of species divergence. Especially
      the internal transcribed spacers (ITS) are very useful for molecular diagnostic
      of parasite. They are noncoding regions of DNA sequence that separate genes
      coding for the 28S, 5.8S, and 18S ribosomal RNAs. These ribosomal RNA (rRNA)
      genes are highly conserved across taxa while the spacers between them may be
      species-specific. In this paper authors describe practical using of rRNA gene to
      parasite diagnostic.

PMID- 17432617
TI  - [Search for protective antigens of hookworms].
AB  - Hookworms are very important blood sucking nematode parasites of humans and
      domestic animals. The host with a heavy infection can lose almost a cup of blood
      per day. This may contribute to anemia which is associated with many physical and
      mental developmental insults. The works on obtaining an effective hookworm
      vaccine have been lasting for about eighty years. Recent identifications of a
      number of bioactive molecules produced by larval and adult stages of
      Ancylostomatidae are very helpful for selecting of nematode proteins crucial for
      host-parasite interactions and promising vaccine antigens. Many of these
      molecules are involved in host skin penetration by infective larvae, intestinal
      tissue invasion and digestion of haemoglobin and/or other macromolecular
      substrates. However, the results of many vaccination trials using recombinant
      forms of these proteins showed no sufficient protection against experimental
      hookworm infections.

PMID- 17432618
TI  - Computational analysis of Ancylostoma ceylanicum cysteine proteinase.
AB  - The potential tertiary structure of Ancylostoma ceylanicum cysteine proteinase
      was obtained by Automatic Program 3D-JIGSAW and used for finding homologues of
      known structure by VAST program. The results of computational analysis showed the
      presence of domains recognizing host immunoglobulins. Based on this analysis we
      suggest that this protein is involved in cleaving of host antibodies and
      therefore it may be promising vaccine candidate. In this paper we present the
      computational analysis of parasitic antigen which is very helpful in evaluation
      of the potential role of this protein.

PMID- 17432619
TI  - Activity of superoxide dismutase in Galleria mellonella larvae infected with
      entomopathogenic nematodes Steinernema affinis and S. feltiae.
AB  - BACKGROUND: The influence of infection with two species of entomopathogenic
      nematodes of Steinernematidae family on the activity of superoxide dismutase
      (SOD) of the host was studied. MATERIAL AND METHODS: Last instar larvae of
      Galleria mellonella were experimentally infected with Steinernema affinis and S.
      feltiae at 20 invasive juveniles per insect. At 6, 12, 18, 24 and 36 h after
      infection activity of SOD was determined in extracts from infected and control
      insects. RESULTS: The activity of SOD decreased gradually in the controls during
      the experiment. The activity of enzyme was 2-4-times higher in insects from both
      infected groups than in the control. During the first 12 h of infection the
      activity of SOD in insects infected with S. feltiae was higher than in those
      infected with S. affinis, then the activity of enzyme in the insects of both
      infected groups stayed at a similar level. A significant decrease of SOD activity
      in infected was recorded in second day of the infection.

PMID- 17432620
TI  - Infection with Echinococcus granulosus (Batsch, 1786) and expression of
      superoxide dismutase gene at mRNA level in hepatocytes.
AB  - Superoxide dismutase (SOD) plays an important role in detoxication of the
      organism. Its function is to protect the organism against the cytotoxic action of
      free radicals. The highest expression of superoxide dismutase was observed in the
      hepatocytes adjacent to the hydatid cyst. The expression of this gene in the
      hepatocytes of infected livers 5 cm apart from the infection site was slightly
      lower.

PMID- 17432621
TI  - Cleavage in Ixodes ricinus (L.) (Acari: Ixodidae).
AB  - The author analyzed the first 5 days of embryonic development of Ixodes ricinus.
      The cleavage takes 4 days, being terminated on the 5th day of embryogenesis, when
      the cells start to invaginate and differentiate. The karyomeres play a role in
      the initial mitotic divisions. Cellularization occurs on the 2nd and 3rd day of
      embryogenesis. The blastoderm cells maintain their potential for division, and as
      from the 5th day cellular differentiation starts.

PMID- 17432622
TI  - [RAPD differentiation of yeast like fungi Malassezia pachydermatis].
AB  - The aim of the work was analyzing of genomic DNA of Malassezia pachydermatis
      isolates from clinical cases otitis externa from dogs using RAPD method with
      arbitrary primers Eric 1R, Eric2, BG2 and FM1. MATERIALS AND METHODS: 47 strains
      of M. pachydermatis isolates from clinical cases otitis externa from dogs were
      tested. Isolation of genomic DNA was provided according with MasterPureTM Yeast
      DNA Purification Kit EPICENTRE procedure. The quality of isolated genomic DNA was
      determined electrophoreticaly. For differentiation the following primers were
      used: Eric1R, Eric2, BG2 and FM1. Primers Eric 1R and Eric 2 were used together
      in one reaction or amplificated separately. Obtained products were analyzed
      electrophoreticaly in 1.5% agarose gel. For determination of phylogenic tree
      Quantity one VersaDoc (BioRad) and Statgraphics plus 4.1 programs were used.
      RESULTS: High degree of heterogeneity of DNA among investigated isolates of M.
      pachydermatis was shown using FM1 primer. Dendrograms were prepared by
      calculation euclid's distance of different parameters (size and count of RAPD
      products) by nearest neighbor method. Basing on phylogenic tree four main types
      (phylogenic groups) of M. pachydermatis isolates were shown. The other five
      groups non-count was shown also.

PMID- 17432623
TI  - [Influence of vaccination of calves with recombinant cysteine proteinase of
      Fasciola hepatica on development and infectivity of miracidia].
AB  - The aim of the study was to evaluate an influence of vaccination of the final
      host on F. hepatica development in intermediate hosts. Fluke eggs were isolated
      from the biliary tracts of calves vaccinated orally with recombinant cysteine
      proteinase of F. hepatica after the challenge infection and from control calves
      which received the infection only. To asses the effect of the vaccine on egg
      "hatch rate" the eggs were transferred to the Petri dishes with distilled water
      and incubated at 25 degrees C for 16-19 days. They were subsequently exposed to
      light for about 2 h, at a temperature of 27 +/- 1 degrees C, to stimulate
      sprouting of the miracidia and asses the egg hatchability. In order to evaluate
      infectivity and pathogenicity of the miracidia, single miracidium infections of
      Lymnea truncatula by F. hepatica were carried out under laboratory conditions
      using 4-mm-high snails. The prevalence of snail infections with F. hepatica was
      calculated using the ratio between the number of cercariae-shedding snails in
      each group and that of surviving snails. It appeared that the eggs isolated from
      immunized calves demonstrated significantly lower hatchability than the eggs
      isolated from non-vaccinated control hosts. Also, the proportion of infected
      snails as well as their mortality were lower after exposition to miracidia
      originating from vaccinated calves. It is suggested that effectors of the immune
      response in vaccinated calves inhibited in part biological activity of cysteine
      proteinases of the fluke which are known to be involved in egg shell formation,
      penetration of host's tissues and worm feeding.

PMID- 17432624
TI  - [Prevalence of Giardia intestinalis in domestic dogs in Warsaw].
AB  - INTRODUCTION: Giardia intestinalis is the most common intestinal protozoan
      parasite, which infects humans, dogs and other mammals throughout the world. So
      far eight genotypes of the parasite have been described of which four were found
      in dogs. Assemblages A-I and B infect either dogs or humans. Assemblages C and D
      occur only in dogs. The aim of the study was to determine the prevalence and
      genotypes of G. intestinalis in domestic dogs of Warsaw area. MATERIAL AND
      METHODS: From October 2005 to March 2006 fecal samples were collected from 350
      dogs and examined using light microscopy and PCR techniques. RESULTS: 5.14% of
      dogs was found to be positive for G. intestinalis by microscopy and prevalence of
      9.14% was found by PCR. The PCR amplicons were sequenced and the DNA sequences
      were compared with Giardia sequences in GeneBank database. The analysis revealed
      assemblage A-I in 1.71% of dogs, assemblage C in 1.14% and assemblage D in 6.28%
      of dogs in Warsaw. According to literature, the genotype A can infect humans
      however a role of dogs as a reservoir of human giardiosis in Poland is not known.

PMID- 17432626
TI  - The first record of Aelurostrongylus abstrusus (Angistrongylidae: Nematoda) in
      Eurasian lynx (Lynx lynx L.) from Poland based on fecal analysis.
AB  - MATERIAL: Thirty eight fecal samples of Eurasian Lynx (Lynx lynx L.) collected in
      Bialowieza Primeval Forest (E Poland) in years 2001-2004 were analysed. RESULTS:
      The presence of Aelurostrongylus abstrusus (L1) larvae was evidenced by use of
      decantation and flotation methods. The general prevalence of the infection
      recorded during the study was 21.1%, whereas mean intensity was 11,5 (1-33 larvae
      per sample). To our knowledge, this is the first case of Aelurostrongylus
      abstrusus recorded in Euroasian lynx from Poland.

PMID- 17432625
TI  - [Molecular and morphological comparison of hookworms from genus Uncinaria
      invading red fox (Vulpes vulpes) and dog (Canis familiaris)].
AB  - Two species of hookworms from genus Uncinaria have been found so far in Poland.
      Uncinaria stenocephala infects mainly dog, wolf and red fox, whereas Uncinaria
      criniformis is a parasite of mustelids (but it was also reported from red fox).
      19 male and 29 female hookworms from red foxes have been compared with 10 male
      and 12 female worms from dogs. Hookworms from dogs were generally smaller than
      these from foxes, but no other morphological differences could be found. These
      hookworms were qualified to species Uncinaria stenocephala on the ground of
      morphology of male. Genomic DNA samples have been isolated from these hookworms
      and segments of rDNA including part of small subunit of ribosomal RNA gene;
      internal transcribed spacer 1 (ITS1); 5.8 S ribosomal RNA; internal transcribed
      spacer 2 (ITS2) and part of large subunit of ribosomal RNA have been amplified
      and sequenced. Sequences from Uncinaria obtained both from foxes and dogs have
      shown very high similarity to the sequence of Uncinaria stenocephala, so all
      examined hookworms have been classified as belonging to this species.

PMID- 17432627
TI  - Occurrence of roundworm (Parascaris equorum) in horses from small farms based on
      necropsy.
AB  - BACKGROUND: The objective of this study was to evaluate the level of roundworm
      infection in working horses slaughtered for meat. In these horses anthelmintics
      had not been used. MATERIAL AND METHODS: Roundworms were collected post-mortem
      from small intestines of 83 horses. RESULTS: The mean prevalence of roundworm
      infection was 12% and intensity--46.7 specimens per horse. Infection was found
      only in foals; 10 animals were infected (45.4%) among the 22 examined. Due to
      common occurrence of roundworms (Parascaris equorum) in foals this nematode
      control should focus particularly on regular anthelmintic treatment of young
      horses, providing proper hygienic conditions for them and checking the infection
      level by coproscopical methods.

PMID- 17432628
TI  - [Gastrointestinal parasites of rabbits in coproscopic investigations].
AB  - BACKGROUND: Parasitological screening was carried out in a breeding herd of the
      New Zealand White rabbit breed in 2004. MATERIAL AND METHODS: Mothers, together
      with their offsprings, were kept in boxes on deep litter, whereas young rabbits
      were transferred to cages with slatted floor. All the animals were fed a complete
      balanced pelleted feed with two coccidiostats added alternately (Lerbec,
      Robenidine), and droplet watering system was applied. No anthelmintic was used in
      the rabbitry. A total of 170 individual samples of fresh feces from females of
      breeding stock, and 55 pooled samples in the case of young animals 2-4 months of
      age, collected on a month intervals, were analyzed according to a modified
      concentration McMaster's method, using saturated salty water with sugar as a
      flotation fluid. RESULTS: The presence of several species of coccidia was
      evaluated, with Eimeria stiedae, E. perforans, E. media and E. magna being found
      in great numbers. The dynamics of infection showed that both adults and young
      animals were affected by coccidia mostly in May (mean intensity reached at that
      time 24000 opg in young rabbits), and then until August the infection lasted on a
      high level. As regards coccidiosis, parasitism could be considerably cut back in
      the herd by frequent changing of the straw litter, which should also always be
      dry. Only Passalurus ambiguus was found from nematodes, and only in the feces of
      adults, probably due to the modern forage and watering system applied, which
      broke the other worms' life cycles.

PMID- 17432629
TI  - Enterobiosis--analysis of infections in human populations of villages and towns
      and infections in families.
AB  - The study presents the results of a research on the frequency of infection with
      Enterobius vermicularis in different urban and rural human populations, conducted
      by Zoology Department of Podlaska Academy in Siedlce between 1998 and 2006. Since
      2001, samples from one examinee were collected seven times. On the basis of the
      seven tests, a table of the frequency of infection and the efficiency of its
      detection was presented. The study indicates the populations in which all the
      infected were detected earlier than after the seventh test. It also presents the
      results of family infection examination (there were two groups of the examined: A
      -only children, B--children as well as parents): out of 125 families 47 (37.6%)
      were infected. The author concluded that the method of taking pinworm samples
      should be standardized to the Graham method with the samples collected on seven
      consecutive days, and that whole families should be examined wherever one person
      is detected to be infected.

PMID- 17432631
TI  - Advancing evidence-based practice.

PMID- 17432632
TI  - Therapeutic use of assistive technology: a clinical perspective.
AB  - Healthcare providers involved in patient handling activities are at risk for
      injury. One solution to minimize this risk is the use of assistive equipment.
      However concern exists that use of assistive equipment may minimize the
      rehabilitation potential of patients compared to using manual handling skills and
      other traditional techniques. Practical examples are provided of how typical
      assistive equipment can actually enhance patient rehabilitation while also
      preventing caregiver injury.

PMID- 17432633
TI  - Social isolation: a practical guide for nurses assisting clients with chronic
      illness.
AB  - Social isolation is a serious problem in our society, and the chronically ill are
      especially vulnerable. The lack of needed and wanted social contacts is a serious
      source of discomfort that can lead to further health problems. Many factors are
      involved, including limited mobility, lack of transportation, apparent and hidden
      disabilities that are socially undesirable, lack of employment, drained
      relationships with caregivers, changes of social roles, and emotional and
      psychological stress and dysfunction. Nurses are in a unique position to
      intervene on behalf of those social isolates. Practical interventions include
      contacting peer counselors, referring the patient to a support group, helping to
      rebuild the family network, enhancing the patient's spirituality, helping the
      patient use Internet-based supports, and practicing the therapeutic use of self
      Social isolation is a threatening condition for many people, but it has many
      solutions. In order to provide holistic care, nurses can address this problem on
      an individual and societal level.

PMID- 17432634
TI  - The experience of adolescent women living with spina bifida part I: self-concept
      and family relationships.
AB  - Adolescent women with spina bifida (SB) face unique and diverse challenges. The
      purpose of this qualitative component of a larger mixed-method study on
      adaptation was to heighten rehabilitation nurses' understanding of self-concept
      and family relationships during adolescence. Interviews were conducted with 31
      adolescent women and analyzed for themes. The women described a range of
      experiences, including challenges of typical adolescence, specific concerns about
      living with SB, school-based stressors, and incidences of teasing and bullying.
      The overall self-concept was primarily positive, despite the diverse stressors
      encountered. A significant source of strength was the close relationships with
      parents, although an undercurrent of tension related to independence was also
      expressed. Results from this study support the need for rehabilitation nurses to
      address not only the functional status but also the well-being and psychosocial
      challenges of adolescent women with SB.

PMID- 17432635
TI  - Problem-solving early intervention: a pilot study of stroke caregivers.
AB  - Caregivers (CGs) of stroke survivors assume their role suddenly and with little
      preparation. Negative emotions are common, persist over time, and are related to
      other negative outcomes. This pilot study, guided by a coping model, examined the
      efficacy and durability of a caregiver problem-solving intervention (CPSI) on CG
      and stroke survivor outcomes. Additional aims included assessment of feasibility
      issues and reliability and sensitivity of the study measures. The nonrandom
      sample of 15 stroke CGs was matched on depression and demographics with a
      comparison group. The CPSI started during acute rehabilitation and continued
      through 2 months after discharge. Parametric and nonparametric tests were used to
      assess achievement of the aims. CG depression, anxiety, preparedness, and
      survivor motor function improved significantly in the intervention group over
      time. Burden, life changes, and taking care of CG's own needs did not change
      significantly. CPSI group CG depression significantly improved compared with the
      matched group. The improvement in outcomes for the CPSI group supports further
      testing of the intervention with a large sample.

PMID- 17432636
TI  - Interpreting laboratory values in the rehabilitation setting.
AB  - Treating patients in rehabilitation settings is becoming increasingly complex for
      a variety of reasons, such as the presence of several comorbid conditions,
      increased age, and earlier discharge from acute care facilities. As a result,
      careful monitoring and assessment by nurses is essential. Laboratory testing can
      improve the assessment when nurses are able to recognize when and what should be
      reported and what types of treatments may be needed. Understanding what
      laboratory findings should be monitored and what added assessment criteria are
      necessary can be daunting. Therefore, this article reviews critical laboratory
      and other assessment findings in light of common health problems faced by
      patients in rehabilitation settings. A case study is used to highlight the
      importance of laboratory testing.

PMID- 17432637
TI  - [Transient analgesic effect of electroacupuncture at Taiyang (EX-HN 5) for
      treatment of migraine with hyperactivity of the liver-yang].
AB  - OBJECTIVE: To explore the difference of therapeutic effects between
      electroacupuncture (EA) and medication for treatment of migraine with
      hyperactivity of the liver-yang. METHODS: With 3-center randomized controlled
      study method, 300 cases were assigned to a treatment group and a control group,
      150 cases in each group. They were treated respectively with EA at Taiyang (EX-HN
      5) and oral administration of western medicine. Changes of the score for headache
      intensity, remission degree of headache and remission rate of headache after
      treatment were investigated. RESULTS: After once treatment, VAS score of the
      headache intensity showed dynamical decrease in the two groups; in the treatment
      group the score reached the lowest 3-4 h after treatment, with the decreasing
      degree better than the control group (P < 0.01). The lasting time of headache
      remission was (388.6 +/- 430.1) min and (163.3 +/- 182.3) min, respectively, the
      treatment group being significantly longer than that of the control group (P <
      0.01). CONCLUSION: EA at Taiyang (EX-HN 5) has transient analgesic effect for
      treatment of migraine with hyperactivity of the liver-yang, which is better than
      that of routine western medication.

PMID- 17432638
TI  - [Observation on therapeutic effect of eye-needling combined with medication for
      treatment of ophthalmoplegia].
AB  - OBJECTIVE: To observe the therapeutic effect of eye-needling combined with
      medication for treatment of ophthalmoplegia and explore the possible mechanism.
      METHODS: One hundred and twenty cases were randomly divided into a treatment
      group and a control group. According to etiological factors, the control group
      were treated with medication and the treatment group with the medication plus eye
      acupuncture at main point ocular muscles. Changes of the rima oculi, the range of
      ocular movement and the dialopia angle after treatment were recorded and
      statistically analyzed in the two groups. RESULTS: The total effective rate was
      93.4% and the cured rate was 54.1% in the treatment group, and 74.6% and 18.6% in
      the control group, with significant difference between the two groups (P < 0.
      01). CONCLUSION: Eye-needling combined with medication has an obvious therapeutic
      effect which is better than simple medication for ophthalmoplegia.

PMID- 17432639
TI  - [Clinical observation on effects of acupuncture at Dazhui (GV 14) for abating
      fever of common cold].
AB  - OBJECTIVE: To explore the therapeutic effect of acupuncture at Dazhui (GV 14) for
      abating fever of common cold. METHODS: Two hundred and sixty-one cases were
      randomly assigned to a treatment group of 133 cases and a control group of 128
      cases. The treatment group were treated with electroacupuncture at Dazhui (GV 14)
      and the control group with antondine injection. The transient effect of abating
      fever within 24 h was observed. RESULTS: After treatment, the body temperature at
      all observation time points in the treatment group were lower than those in the
      control group (P < 0.01). The effect-appearing time (1.42 +/- 1.79) h in the
      treatment group was shorter than that in the control group (3.44 +/- 5.10) h (P <
      0.01). The cured rate and the abating fever rate were 27.8% and 75.9% in the
      treatment group, and 10.9% and 55.5% in the control group, with significant
      differences between the two groups, the treatment group being better than the
      control group (P < 0.01). The abating fever rate for the wind-heat type common
      cold was 75.3% in the treatment group and 50.0% in the control group, with
      significant difference between the two groups, the treatment group being better
      than the control group (P < 0.01). CONCLUSION: The method of acupuncture at
      Dazhui (GV 14) has a definite therapeutic effect on high fever of common cold,
      and for wind-heat type common cold, Dazhui (GV 14) first may be chosen to abate
      high-fever and the treatment should be taken as early as possible.

PMID- 17432640
TI  - [Clinical observation on different acupuncture and moxibustion therapies for
      treatment of postsurgical gastroparesis syndrome].
AB  - OBJECTIVE: To optimize therapy of acupuncture and moxibustion for postsurgical
      gastroparesis syndrome (PGS). METHODS: Forty-one cases of PGS were randomly
      divided into 3 groups in order of visiting. Group A (n = 17) were treated by
      warming needle moxibustion, group B (n = 12) by acupuncture plus auricular point
      sticking, and group C (n = 12) by routine acupuncture. Changes of gastric
      drainage volume, therapeutic times and cured rate were investigated in the 3
      groups. RESULTS: All the 3 therapeutic methods could significantly decrease
      gastric drainage volume. The cured rate was 100.0% and the therapeutic times was
      (7.24 +/- 3.87) in the group A, 66.7%, (9.83 +/- 4.60) times in the group B and
      75.0%, (15.25 +/- 3.81) times in the group C, with significant differences in the
      cured rate and the therapeutic times among the 3 groups (P < 0.05, P < 0.01).
      CONCLUSION: The warming needle moxibustion is the best method for PGS, with less
      therapeutic times, high cured rate and rapid effect.

PMID- 17432641
TI  - [Observation on clinical therapeutic effect of Yang's cotton moxibustion on
      neurodermatitis].
AB  - OBJECTIVE: To compare the difference of the therapeutic effects between Yang's
      cotton moxibustion and hormonotherapy on neurodermatitis. METHODS: Sixty cases of
      neurodermatitis were divided into a treatment group and a control group according
      to random number table. The treatment group were treated with Yang's cotton
      moxibustion and the control group with triamcinolone and urea cream. After
      treatment for one week, the therapeutic effect was start to be observed. After
      the treatment was given for 4 weeks, the therapeutic effect was evaluated.
      RESULTS: The total effective rate was 93.3% in the treatment group and 80.0% in
      the control group, with a significant difference between the two groups (P <
      0.05). CONCLUSION: Yang's cotton moxibustion has an obvious therapeutic effect on
      neurodermatitis with a good safety.

PMID- 17432642
TI  - [Effects of the improved acupoints and rehabilitation exercise on locomotor
      ability of the upper limbs and ability of daily life in the patient of cerebral
      infarction].
AB  - OBJECTIVE: To search for an effective method for improving locomotor ability of
      upper limbs and ability of daily life in the patient of cerebral infarction.
      METHODS: Five hundred and seventy-eight cases of stroke were randomly divided
      into 4 groups: an improved acupoints and rehabilitation exercise group (group A,
      n = 148), a rehabilitation exercise group (group B, n = 142), a routine acupoints
      and rehabilitation exercise group (group C, n = 144), and a medication group
      (group D, n = 144). The locomotor ability of the upper limbs and ability of daily
      life were evaluated respectively by Fugl-Meyer (FMA) and Barthel (BMI). RESULTS:
      There were significant differences in FMA and BMI scores in all the groups after
      treatment as compared with those before treatment (P < 0.05); after treatment,
      the effect in the group A was significantly superior to those in group B and C (P
      < 0.05), with no significant difference between the group C and the group B.
      CONCLUSION: The improved acupoints combined with rehabilitation exercise can
      improve locomotor ability of the upper limbs and ability of daily life in the
      patient of cerebral infarction.

PMID- 17432643
TI  - [Clinical observation on deeply needling Ciliao (BL 32) for treatment of prolapse
      of lumbar intervertebral disc].
AB  - OBJECTIVE: To explore specificity of acupoints for treatment of prolapse of
      lumbar intervertebral disc. METHODS: One hundred and eighty cases were randomly
      divided into a treatment group (n = 120) and a control group (n = 60). The two
      groups were treated with acupuncture, traction and massage therapy. For the
      treatment group, routine acupoints were selected and deeply needling Ciliao (BL
      32) were added. For the control group, only routine acupoints were needled. And
      other treatments were same in both the two groups. RESULTS: The total effective
      rate was 97.5% in the treatment group and 88.3% in the control group, with a
      significant difference between the two groups (P < 0.05); after following survey
      of a half year, the recurrence rate was 8.6% in the treatment group and 20.8% in
      the control group, with a significant difference between the two groups (P <
      0.05). CONCLUSION: The clinical effect of deeply needling Ciliao (BL 32) as main
      therapy is significantly better than that of the routine selection of acupoints,
      with a lower recurrence rate.

PMID- 17432644
TI  - [Clinical observation on auricular-plaster therapy combined with chiropractics
      for treatment of emaciation in children].
AB  - OBJECTIVE: To search for a non-medicine therapy for infant emaciation. METHODS:
      The observation group of 55 cases were treated with auricular point sticking
      combined with chiropractics. For the auricular point sticking therapy, vaccaria
      seeds were stuck at 9 points such as small intestine, Shenmen, spleen, endocrine,
      and others, and replaced once every 5 days, 10 days constituting one course.
      Chiropractics: knead or massage the muscles from lumbosacral area upward to
      Dazhui (GV 14). The control group were treated with oral administration of pepsin
      mixture, 10 mL after meals, thrice each day. They were treated for 5 courses.
      RESULTS: Of the 55 cases in the observation group, 7 were cured, 20 markedly
      effective, 24 effective and 4 ineffective, with a total effective rate of 92.7%,
      and among the 23 cases in the control group, 2 cases were cured, 7 markedly
      effective, 8 effective and 6 ineffective, with a total effective rate of 73.9%.
      CONCLUSION: Auricular point sticking combined with chiropractics is a better non
      medicine therapy for emaciation in children.

PMID- 17432646
TI  - [Observation on the therapeutic effect of warming needle moxibustion on knee
      osteoarthritis].
AB  - OBJECTIVE: To compare clinical therapeutic effects of warming needle moxibustion
      and acupuncture plus TDP radiation on knee osteoarthritis. METHODS: Eighty cases
      conforming with the diagnostic criteria for knee osteoarthritis were randomly
      divided into a warming needle moxibustion group and an acupuncture plus TDP
      radiation group. In the two groups, Dubi (ST 35), Xiyan (EX-LE), Yanglingquan (GB
      34),etc. were selected and the treatment was given once every other day, 10
      sessions constituting one course. After treatment of 2 courses, their therapeutic
      effects were compared. RESULTS: The clinically basic recovery rate was 30.0% in
      the warming needle moxibustion group and 10.0% in the acupuncture plus TDP
      radiation group, with a very significant difference between the two groups (P <
      0.01). CONCLUSION: Warming needle moxibustion is an effective therapy for knee
      osteoarthritis.

PMID- 17432645
TI  - [Observation on the therapeutic effect of acupoint application on constipation].
AB  - OBJECTIVE: To test the therapeutic effect, safety of acupoint application for
      treatment of constipation. METHODS: Forty-two cases were randomly divided into a
      treatment group of 22 cases and a control group of 20 cases. The treatment group
      were treated with acupoint application, with the cake made by Sanleng (Rhizoma
      Spargani), Ezhu (Rhizoma Zedoariae), Dahuang (Radix et Rhizoma Rhei) and Bingpian
      (Borneolum), which was applied at Tianshu (ST 25), Qihai (CV 6), Guanyuan (CV 4);
      the control group were treated with oral administration of Congrong Tongbian Oral
      Liquid. RESULTS: The total effective rate was 81.8% in the treatment group and
      50.0% in the control group, the treatment group being better than the control
      group (P < 0.05); the first defecation time was (5.1 +/- 2.8) h in the treatment
      group and (10.1 +/- 7.3) h in the control group, with a significant difference
      between the two groups (P < 0.05). CONCLUSION: TCM acupoint application therapy
      has a definite therapeutic effect on constipation.

PMID- 17432647
TI  - [The role of connexin 43 gene in acupuncture analgesia].
AB  - OBJECTIVE: To investigate the possible relationship between the analgesic effect
      of acupuncture and connexin 43. METHODS: Connexin 43 gene knock-out mice were
      divided into 4 groups: a wide type (WT) control group, a WT acupuncture group, a
      heterozygous (HT) control group and HT acupuncture group. Hot-plate test and
      writhing response induced by acetic acid were used for investigating the
      analgesic effect of acupuncture. RESULTS: There was no significant difference in
      the basic pain threshold value between HT and WT mice (P > 0.05). Acupuncture
      could significantly increase the pain threshold value, prolong the latency period
      of writhing body and decrease the number of writhing body as compared with pre
      acupuncture in WT and HT mice (P < 0.01 or P < 0.05). The pain threshold, latency
      period of writhing and number of writhing body in HT mice were less than WT mice
      post-acupuncture (P < 0.05). CONCLUSION: Connexin 43 gene knock-out might
      partially inhibit the analgesic effect of acupuncture, suggesting that connexin
      43 is possibly related with meridians and the effect of acupuncture.

PMID- 17432648
TI  - [Clinical application of acupoint heat-sensitization].
AB  - OBJECTIVE: To expound rules of acupoint heat-sensitization and its clinical
      application. METHODS: Analyze and probe rules of acupoint heat-sensitization and
      its clinical application from the acupoint heat-sensitization phenomenon.
      RESULTS: (1) In the human being there are two functional states, sensitization
      state and rest state. When the human body has disease, acupoints on the body
      surface may be sensitized with various types of sensitization, and acupoint heat
      sensitization is a type of acupoint sensitization. The sensitized acupoints show
      acupoint-specific "small stimulation inducing large response" for external
      relative stimulation. (2) Optimum stimulation for the heat-sensitized acupoint is
      moxibustion-heat, also it is the optimum point for moxibustion therapy, with a
      therapeutic effect far better than acupuncture and moxibustion at acupoints of
      routine rest state. (3) Heat-sensitized acupoints under moxibustion-heat
      stimulation very easily invigorates moxibustion sensation propagation along
      channels, greatly increasing clinical therapeutic effect. CONCLUSION: Advancing
      the concept of acupoint heat-sensitization perfects and develops the theory of
      acupuncture and moxibustion, "Only reaches the needling sensation to the affected
      area, can the needling produce effects".

PMID- 17432649
TI  - [Effects of acupuncture at the points of the Pericardium Meridian on the activity
      of myocardial Ca2+-ATPase and gene expression in the rat of myocardial ischemia
      and reperfusion injury].
AB  - OBJECTIVE: To investigate the mechanism of acupuncture at "Neiguan" (PC 6) and
      "Ximen" (PC 4) of the Pericardium Meridian in treatment of myocardial ischemia.
      METHODS: Rats were randomly divided into 5 groups, sham-operation group, ischemia
      reperfusion model group, Neiguan acupuncture group, Ximen acupuncture group and
      Zhigou acupuncture group. Electroacupuncture (EA) was given at corresponding
      acupoints for 20 min in the later 3 groups, followed by ligation of the left
      anterior descending branch of the coronary artery and 40 min later, acupuncture
      was given at the points for another 20 min, reperfusion for 60 min, with ECG
      monitoring. Then the myocardial tissue sample (below the ligation site) of the
      left cardiac ventricle was taken for preparation of sarcoplasmic reticulum, and
      determination of Ca2+-ATPase activity according to quantitative analysis of
      phosphorum. The relative mRNA levels were determined by Northerm Bolt analysis.
      RESULTS: In the acupuncture groups, both the activities of Ca2+-ATPase and the
      gene expressions increased significantly as compared with the model group (all P
      < 0.01). CONCLUSION: The points of the Pericardium Meridian can obviously improve
      the Ca2+-ATPase activity and the gene expressions, reduce the degree of
      myocardial ischemia and reperfusion injury, and strength myocardial functions.

PMID- 17432650
TI  - [Observation on acupuncture at "Neitinggong" for antagonisting ototoxicity caused
      by gentamicin].
AB  - OBJECTIVE: To explore the effect of acupuncture at "Neitinggong" drug-induced
      deafness. METHODS: Guinea pig deafness model was prepared by injection of
      gentamicin (GM). Acupuncture was respectively given at the points "Neitinggong"
      "Tinggong" (SI 19) and non-acupoints on the auricle in the experimental animals
      in different groups and the effects of different points on the auditory brainstem
      response and cochlear hair cells were observed. RESULTS: There was a significant
      difference between GM group and Neitinggong group, and between GM group and
      Tinggong group. There was no significant difference between GM group and the
      auricle group, and between Neitinggong group and Tinggong group. CONCLUSION:
      Acupuncture at "Neitinggong" can strength the function of the internal ear, and
      relieve the injury of cochlear hair cells caused by gentamicin, which is an
      effective acupoint for treatment of drug-induced deafness.

PMID- 17432651
TI  - [On academic ideas of professor KONG Zhao-xia about acupuncture and moxibustion].
AB  - Ideas of professor KONG Zhao-xia about acupuncture points were explained through
      the discussion of four aspects of meridian points and extra-ordinary points,
      confirmed points and non-confirmed points (Ashi points), located points and the
      area of points, the area of points and area of non-points. Acupoints are the
      special responsive spots of qi and blood on the body surface. All meridian
      points, confirmed points, extra-ordinary points, non-confirmed points possess
      peculiar functions, thus, more attention should be paid to selection and
      combination of points. The size of acupoint area, the therapeutic effects as well
      as acupuncture manipulation depend upon the location of acupoints. Acupuncture
      and moxibustion are two kinds of therapies, and both of them have own
      indications, so, you should attach same importance to the two therapies.
      Acupuncture and moxibustion are important therapeutic techniques and belong to
      external therapies. They could be applied alone, or be used in combination with
      Chinese herbal medicine according to conditions of the patient.

PMID- 17432652
TI  - [The main mechanism of the reinforcing-reducing method in Huangdi's Internal
      Classic is to promote qi with thought].
AB  - Based on Huangdi' s Internal Classic and a great deal of clinical verification,
      in combination with new discoveries of the nerve, the meridian electromagnetic
      field and the quantum physics for role of thought outside body, it is proved that
      the main mechanism of the reinforcing-reducing method in Huangdi's Internal
      Classic is to promote flow of qi with the doctor's thought, with the needle very
      few twisted and rotated; discover new mechanisms of the reinforcing-reducing
      method, newly explain and clinically verify many basic standpoints about the
      reinforcing-reducing, and name as "acupuncture therapy of promoting qi with
      thought". The method has a strong reinforcing-reducing function and do not need
      the needle feeling, and is directly related with doctor's idea. It is emphasized
      specially that it can be carefully adopted only when full syndrome
      differentiation is made and strictly obey the contraindications in Huangdi's
      Internal Classic, otherwise it has very serious danger. This kind of model that
      doctor's mental effect is translated into the patient's biological effect put
      forward new problem, new thinking for brain sciences and modern acupuncture
      studies.

PMID- 17432653
TI  - [Science of Acupuncture Prescription: an innovation teaching material].
AB  - The author introduces the background of writing the innovation teaching material
      Science of Acupuncture Prescription in TCM university and colleges. The
      characteristics of this book were: (1) It establishes the train of thought on
      acupuncture prescriptions mainly based on the location of the acupoints. (2) It
      ascertains the relationship between prescriptions and science of prescription.
      (3) It highlights the scientific property of Science of Acupuncture Prescription
      by organic combination of inheritance and creativity. The publication of Science
      of Acupuncture Prescription serves as a bridge between Science of Meridians and
      Collaterals and Acupoints and Science of Acupuncture Therapy, perfects the course
      system of acupuncture and moxibustion and complements knowledge structure of
      acupuncture and tuinaology, and it also symbolizes the development of acupuncture
      and moxibustion.

PMID- 17432654
TI  - [Analysis on literatures about clinical treatment of low back pain with
      acupuncture and moxibustion published in the periodicals included by SCI in
      recent 5 years].
AB  - OBJECTIVE: To explore the development state of acupuncture and moxibustion
      therapy in the world. METHODS: Retrieve and analyze the literatures about
      clinically treating low back pain with acupuncture and moxibustion published at
      periodicals included by SCI in recent 5 years in Pubmed. RESULTS: Nineteen
      concerned literatures were retrieved. Authors of the literatures come from USA,
      Germany, Hong Kong of China, UK (including Northern Ireland) , Austria, Sweden
      and Italy. The literatures were published at Altern Ther Health Med, Am J Phys
      Med Rehabil, Anesth Analg, Arch Intern Med, Forsch Komplementarmed Klass
      Naturheilkd, Health Technol Assess, Rheumatology (Oxford), South Med J, Spine,
      Complment Ther Med, Pain. Three researches show that efficacy of acupuncture is
      uncertain. Other researches support the efficacy of acupuncture. The researches
      on treating low back pain with acupuncture and moxibustion are still mainly about
      efficacy of the acupuncture and moxibustion therapy. CONCLUSION: The acupuncture
      and moxibustion therapy is still in the process of gradually admitted by
      international medicine.

PMID- 17432655
TI  - [Bibliometrics study on dominant diseases in modern acupuncture clinic].
AB  - OBJECTIVE: To find out the dominant diseases in the clinic of modern acupuncture.
      METHODS: By means of bibliometrics, clinical acupuncture study literatures from
      1978 to 2004, searched from CBM database, were sorted and counted to show the
      different clinical utilizing quantities and developing trends of different
      disease groups in the acupuncture clinic. RESULTS: Obviously dominant type:
      nervous system diseases; mature type: motor system diseases; developing type: 3
      kind of diseases including psychosis; premature type: diseases related with
      surgery; steady type: 3 kind of diseases including digestive system diseases
      (diseases of liver and gallbladder are not included); pre-developing diseases: 5
      kind of diseases including otorhinolaryngologic diseases. CONCLUSION: Among all
      these types, obvious advantage type and mature type are the most distinguishing.
      Developing type has the most significant ascending trend. Premature type has
      relatively strong developing potentiality.

PMID- 17432656
TI  - [Study on the train of thought about study of standardization of the nomenclature
      of acupuncture and moxibustion].
AB  - Acupuncture and moxibustion sciences have a long history, and their unique
      discipline language and theoretical system determine the obvious differences
      between acup-moxibustion sciences and modern natural sciences in the
      nomenclature. Their inheritance and development of several thousand years make
      the complicated nomenclature of acupuncture and moxibustion more confusing,
      unclear classification, unclear definition. Therefore, establishment of a unified
      and standard acupuncture and moxibustion nomenclature system is not only an
      important premise and basis for standardization, modernization,
      internationalization and information construction of acupuncture and moxibustion
      sciences, and also is an important composition of whole TCM standardization. The
      present paper preliminarily probe the necessity, basic principle, train of
      thought and relative problems, etc. in the studies of standardization of the
      nomenclature of acupuncture and moxibustion sciences.

PMID- 17432657
TI  - Infusion pumps: reader challenges JC guidance.

PMID- 17432658
TI  - Can one call do it all? Call center options for healthcare facilities.

PMID- 17432659
TI  - Selecting the right vendor: calibration services in a critical environment.

PMID- 17432660
TI  - Reverse education: a step back to move forward.

PMID- 17432661
TI  - A vendor's perspective...equipment acquisition: how clinical engineering can
      help.

PMID- 17432662
TI  - Fluidics 101 for biomeds.

PMID- 17432663
TI  - Medical-grade workstation security.
AB  - I am delighted to introduce to IT World readers this issue's guest columnist.
      Scott Bradley, BSEE, MEM, is a product manager for networking at Drager Medical.
      He has a great background and experience that I'm happy we're able to take
      advantage of. We can learn from his network management, medical device
      experience, and background in managing security accreditations for PCs and
      networks for the U.S. Army. In this case, we're talking about security with
      medical-grade workstations--something we all need to pay attention to. As Scott
      says, "With the introduction of medical-grade workstations into the information
      infrastructure, maintaining virus-free systems and networks is a fundamental
      responsibility for both the vendor and the healthcare facility. Each has
      mandatory tasks to carry out, essential technology to deploy, and strict policies
      to enforce. Together, they can maintain virus-free environments that promote the
      highest levels of patient care." Thanks, Scott, for a timely, informative, and
      useful IT World!

PMID- 17432664
TI  - "I need this yesterday"...tips on setting priorities.

PMID- 17432665
TI  - Roving BMETs: improving patient safety and satisfaction.

PMID- 17432666
TI  - The nuts and bolts of...screws and washers.

PMID- 17432667
TI  - Computed radiography.

PMID- 17432668
TI  - ANSI/AAMI/ISO 13485 comes of age.

PMID- 17432669
TI  - Lower currents: a new choice for routine testing.
AB  - U.S. NFPA and AAMI standards both recommend a 10A ground bond test and, as has
      been described above, both 25A and 200mA are also recommended internationally as
      valid test currents for the in-service testing and inspection of medical
      electrical equipment. The reality is that both high and low test currents are of
      value to biomedical engineers and technicians in different circumstances. For
      benchtop testing in a workshop environment, where required test currents can be
      applied safely, then it seems likely that high current testing will remain the
      preferred option. However, for in-service test applications, where the
      portability and versatility of the tester is a key requirement, modern electronic
      technology now means that low current testing can now be applied effectively and
      safely. In summary, by using a low-energy, high current pulse prior to 200 mA
      test current, the lower test current is preferred for routine field maintenance
      as this can mean: Increased safety of the operator. Reduced risk of damage to the
      in-service medical equipment. Smaller test instruments to include valid ground
      bond measurements. Battery operated test equipment. Increased flexibility of the
      test engineer due to lightweight test equipment. Cost reduction due to reduced
      down time of medical equipment. More economical availability of test equipment.

PMID- 17432670
TI  - Beyond the Joint Commission: an overview of other inspection systems.

PMID- 17432671
TI  - Examining the new AAMI standard...containment devices for reusable medical device
      sterilization.

PMID- 17432672
TI  - Using voice-recognition technology to eliminate cardiac cycle segmentation in
      automated heart sound diagnosis.
AB  - Advanced digital signal processing has the potential to revolutionize the
      stethoscope through the use of mathematical algorithms to interpret heart sound
      acoustic information. In this study, a novel classification algorithm that does
      not require cardiac cycle segmentation was used for identifying differences
      between normal and diseased heart sounds. The heart sound signals were not
      separated into systole and diastole. A recordable electronic stethoscope was used
      to record the heart sounds of 163 echocardiogram patients. Mel-cepstrum and
      Principal Components Analysis were applied to the 60 recorded heart sounds and
      decision spaces were developed. The algorithm was tested using 100 novel
      patients. The specificity of the algorithm is 72.4% and the sensitivity is 63.4%.

PMID- 17432673
TI  - What makes a successful BMET?

PMID- 17432674
TI  - [Effect of Danzhi Xiaoyao Powder on neuro-immuno-endocrine system in patients
      with depression].
AB  - OBJECTIVE: To observe the effect of Danzhi Xiaoyao Powder (DXP) on neuro-immuno
      endocrine system in patients with depression. METHODS: A randomized double
      blinded and controlled study was conducted in 63 cases of depression. They were
      assigned to the DXP group (32 cases, treated with DXP) and the control group (31
      cases, treated with maprotiline). The curative effect was evaluated with
      Hamilton's depressive scale (HAMD) before and at the end of the 2nd, 4th and 6th
      week of the treatment. Serum levels of serotonin (5-HT), norepinephrine (NE),
      brain derived neurotrophic factor (BDNF), cortisol (CORT), interleukin-6 (IL-6),
      and interleukin-1beta (IL-1beta) were detected before and at the 6th week of the
      treatment. RESULTS: After 2 weeks of treatment, the total score of HAMD decreased
      remarkably in both groups (P < 0.01), and the total score, as well as the scores
      of the three factors, i. e. anxiety/somatization, cognitive impairment and
      feeling of despair, were lower in the DXP group than that in the control group
      respectively (P < 0.05 or P < 0.01). After 4 and 6 weeks of treatment the total
      score and score of the three factors all reduced significantly in both groups (P
      < 0.01), with insignificant difference between the groups. After 6 weeks of
      treatment, the serum levels of 5-HT and BDNF increased (P < 0.01), and the serum
      IL-6 level decreased in both groups (P < 0.05 or P < 0.01), the serum CORT level
      reduced in the DXP group (P < 0.01), while the serum NE level elevated in the
      control group (P < 0.01). CONCLUSION: DXP is effective in improving symptoms of
      depression by regulating the levels of 5-HT, BDNF, CORT and IL-6.

PMID- 17432675
TI  - [Clinical study on "Jin's three-needling" in treatment of generalized anxiety
      disorder].
AB  - OBJECTIVE: To study the clinical effect of "Jin's three-needling" in the
      treatment of generalized anxiety disorder. METHODS: Fifty-eight patients with
      generalized anxiety were randomly assigned to two groups equally, the medication
      group treated with anti-anxiety drugs and the acupuncture group with "Jin's three
      needling". The treatment course was 6 weeks. The clinical effects were evaluated
      with Hamilton anxiety scale (HAMA), clinical global impression (CGI), and
      treatment emergent symptom scale (TESS) before treatment and at the end of 2nd,
      4th, 6th week of the treatment course. The concentration of 5-hydroxytryptamine
      (5-HT) in platelet, and plasma levels of corticosterone (CS) and
      adrenocorticotropic hormone (ACTH) were measured with high performance liquid
      chromatography-electrochemical detection (HPLC-ED) method before and after
      treatment. RESULTS: The clinical effects in the two groups were equivalent, while
      the adverse reaction found in the acupuncture group was less than that in the
      medication group (P < 0.05). The platelet concentration of 5-HT and plasma ACTH
      level decreased significantly in both groups after treatment with insignificant
      difference between the group (P < 0.05). The plasma CS level had no obvious
      change in the two groups after treatment as compared with that before treatment
      respectively. CONCLUSION: "Jin's three-needling" shows similar curative effect on
      generalized anxiety to routine Western medicine but with less adverse reaction,
      which may be realized through regulating the platelet 5-HT concentration and
      plasma ACTH level.

PMID- 17432676
TI  - [Study on integrated Chinese and Western therapy and criterion for efficacy
      evaluation of gastroesophageal reflux disease--a clinical observation on 116
      cases].
AB  - OBJECTIVE: To explore the criterion for efficacy evaluation of gastroesophageal
      reflux diseases (GERD) and the effect of treatment with integrated Chinese and
      Western medicine. METHODS: One hundred and sixteen patients of GERD were randomly
      assigned to two groups, group A treated with Western medicine and group B with
      integrated Chinese and Western medicine. Changes of symptoms, TCM syndromes, and
      endoscopic picture were observed before and after treatment. And the condition of
      recurrence was also inspected. RESULTS: The total effective rate was 84.5% and
      67.2% in group A and B respectively. The long-term efficacy was better in group B
      than that in group A (P < 0.05), while there was no significant difference in
      short-term efficacy between the two groups. But the recurrence happened in both
      groups after withdrawal of treatment. The recurrence rate was significantly
      higher in patients of deficiency syndrome type and coexistence of deficiency and
      excess syndrome type than that in those of excess syndrome type (P < 0.05), and
      it was also higher in those whose pathogenesis was associated with mental factor
      (P < 0.05). In the other 20 patients the treatment was sustained for 10.4 +/-
      11.4 months on average. There were 69.0% of the patients with normal esophagus
      mucosa shown by endoscope examination, and the pathological changes were not
      coincident with the symptoms and prognosis. CONCLUSIONS: Basically, no case of
      GERD could be cured, so, it is supposed that the item of "cure" in the criteria
      of therapeutic efficacy evaluation is advisably made over to "clinical control"
      or "obvious efficacy", and add an item of "no change" in the criterion. The
      importance of endoscopic picture for efficacy evaluation is doubtful and needs to
      be further discussed.

PMID- 17432677
TI  - [Clinical observation on effect of modified Daotan Decoction combined with small
      dose risperidone in treating chronic schizophrenia].
AB  - OBJECTIVE: To evaluate the clinical efficacy of modified Daotan Decoction (DD)
      combining low dosage of risperidone in treating chronic schizophrenia patients of
      phlegm-dampness blockage type, and compare with patients treated with risperidone
      alone. METHODS: Sixty-five inpatients were randomly assigned to two groups, the
      treatment group (34 cases) treated with DD (with conventional dosage) one dose
      per day and risperidone 3.16 +/- 0.73 mg/d, and the control group (31 cases)
      treated with risperidone 5.11 +/- 1.27 mg/d alone, the course for both groups was
      8 weeks. The effect was evaluated with positive and negative syndrome scale
      (PANSS), and the adverse reaction was assessed with treatment emergent symptom
      scale (TESS). RESULTS: There was no significant difference in the overall
      efficacy between the two groups, but the improvement of the negative symptoms,
      illness provocation and general psychopathologic condition was significantly
      better in the treatment group than that in the control group respectively (P <
      0.05). Moreover, the adverse reaction was milder and less in the former than that
      in the latter. CONCLUSION: The treatment of DD combined with low dosage of
      risperidone is effective on chronic schizophrenia and shows less adverse
      reaction.

PMID- 17432678
TI  - [Effects of Shenfu Injection on inflammatory cytokines during
      cardiopulmonarbypass in infants].
AB  - OBJECTIVE: To evaluate the effects of Shenfu Injection (SF) on cytokines during
      cardiopulmonary bypass (CPB) in infants. METHODS: Twenty-four infants with
      congenital heart disease, aged below three years, were randomly assigned to the
      control group and the SF group equally. In the SF group, 1 mL/kg of SF was given
      through center vein pump after center vein puncture being performed, while only
      normal saline was given instead in the control group. Blood sample was obtained
      for measurement of serum necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL
      6) concentration by ELISA, at various time points in the process, i.e. right
      after anesthesia induction (T1), beginning of CPB (T2), aortic off-clamping (T3),
      20 min after CPB (T4), the end of CPB (T5), and 6 h (T6) and 24 h (T7) after CPB.
      RESULTS: The time for reverting to sinus heart rhythm and analepsia after CPB was
      shorter in the SF group than in the control group (P < 0.05). Serum concentration
      of TNF-a and IL-6 was equal in the two groups at T1; they increased significantly
      after CPB (P < 0.05), reached the peak value at T4 and reduced to the normal
      level at T7 in the control group. TNF-alpha concentration was significantly lower
      at T3, T4 and T5, and IL-6 concentration was lower at T4 in the SF group than
      that in the control group at corresponding time point (P < 0.05). CONCLUSION: SF
      could shorten the time for reverting to sinus heart rhythm and analepsia after
      CPB in infants, and suppress the inflammatory response caused by CPB.

PMID- 17432679
TI  - [Effects of acupuncture on quality of life in children with spastic cerebral
      palsy].
AB  - OBJECTIVE: To investigate the effect of acupuncture in children with spastic
      cerebral palsy (SCP). METHODS: One hundred SCP children, 2 to 7 years old, were
      randomly assigned to two groups equally. The control group was treated with
      rehabilitation training using Bobath and Vojta physical training methods and the
      acupuncture group treated also with the same training but with acupuncture
      conducted additionally. The therapeutic course was 3-12 months arranged according
      to the state of illness. RESULTS: The total effective rate, development quotient
      (DQ), improvement rate of brain hypogenesis and atrophy showed by skull CT, and
      recovery rate of cerebral emission computed tomography (ECT) were all higher in
      the acupuncture group than those in the control group (all P < 0.01). CONCLUSION:
      Acupuncture obviously promotes the compensation of cerebral function and shows a
      favorable effect in improving quality of life of the children with SCP.

PMID- 17432680
TI  - [Clinical observation on total glucosides of paeony combined with sulfasalazine
      in treatment of ankylosing spondylitis].
AB  - OBJECTIVE: To evaluate the efficacy and adverse reaction of total glucosides of
      paeony (TGP) combined with sulfasalazine (SSZ) in the treatment of ankylosing
      spondylitis (AS). METHODS: Sixty-seven AS patients were randomly assigned to 2
      groups: the treatment group (34 cases) treated with TGP and SSZ, the control
      group (33 cases) with methotrexate (MTX) and SSZ. Changes of clinical efficacy
      related indexes including lumber pain index, morning stiffness time, peripheral
      joint pain index, thoracic expansion, Schober test, Bath AS disease active index
      (BASDAI), Bath AS functional index (BASFI), the levels of erythrocyte
      sedimentation (ESR) and C-reactive protein (CRP), and X-ray of sacroiliac joint
      were observed. RESULTS: The clinical efficacy indexes were significantly improved
      after treatment in the two groups (P < 0.05). Except that the improvement of
      lumber pain index and peripheral joint pain index was better in the treatment
      group than that in the control group (P < 0.05), no significant difference was
      found in the other indexes between the two groups. The occurrence of adverse
      reation was less in the treatment group than in the control group (P < 0.05).
      CONCLUSION: TGP treatment combined with SSZ shows favorable effect on AS with
      less and milder adverse reaction.

PMID- 17432681
TI  - [Effect of Xuezhikang on cardiac function, serum C-reactive protein and blood
      lipid in patients with chronic heart failure].
AB  - OBJECTIVE: To evaluate the effect of Xuezhikang (XZK) on cardiac function and
      serum C-reactive protein (CRP) in patients with chronic heart failure (CHF).
      METHODS: Sixty-eight CHF patients were randomly assigned to two groups, the
      control group (30 cases) treated with angiotensin converting enzyme inhibitor,
      beta-receptor inhibitor, digoxin and diuretic, and the treated group (38 cases)
      with the above treatment plus XZK for six months. The changes of cardiac function
      and serum CRP level were measured by echocardiography and enzyme-linked
      immunosorbent assay (ELISA) respectively before and after treatment. RESULTS:
      Compared with those before treatment, the NYHA cardiac function grade, the left
      ventricular dimension end diastole (LVDd), and the left ventricular dimension end
      systole (LVDs) decreased significantly (P < 0.05), and the ejection fraction (EF)
      and E/A ratio increased significantly in both groups after treatment (P < 0.05) ,
      however, the decrement or increment was more significant in the treated group
      than that in the control group respectively (P < 0.05); the serum CRP level
      decreased significantly in the treated group after treatment and showed a level
      obviously lower than that in the control group (P < 0.05), which changed
      insignificantly after treatment. CONCLUSION: Xuezhikang could improve cardiac
      function and decrease serum CRP level at the same time.

PMID- 17432682
TI  - [Experimental study of Qishen Yiqi Dropping Pills on liver fibrosis in rats].
AB  - OBJECTIVE: To investigate the anti-fibrotic effects of Qishen Yiqi Dropping Pills
      (QYDP) in rats with liver fibrosis (LF). METHODS: The LF model was induced by
      intraperitoneal injection with dimethylnitrosamine (DMN). Sixty Wistar rats were
      randomly divided into the normal group, the model group A, the QYDP intervened
      group , the model group B , and the QYDP treated group B. The degree of LF was
      evaluated according to 6-phase grading method. The expressions of collagen type I
      and III and tissue inhibitor of metalloproteinase-1 (TIMP-1) in liver tissues
      were determined by immunohistochemistry and the levels of collagen type I and III
      and TIMP-1 mRNA determined by semi-quantitive RT-PCR. RESULTS: Compared with the
      model group A and B, the degree of LF, the positive expressions of TIMP-1 mRNA
      and the content of collagen type I and III in liver tissue in the QYDP intervened
      and treated groups were significantly lower. CONCLUSION: QYDP could reduce the
      pathological changes and degree of LF in rats, which may be partially through
      inhibiting the expressions of collagen type I and III and TIMP-1.

PMID- 17432683
TI  - [Characteristics of TCM syndrome and appraisal with echocardiography in heart
      failure rats after myocardial infarction].
AB  - OBJECTIVE: To study the characteristics of the TCM syndrome and the changes of
      ventricular structure and function in heart failure (HF) rats after- myocardial
      infarction (MI). METHODS: Rats were randomly divided in to the model group and
      the sham-operative group. The HF rat with MI model was induced by ligation of the
      left coronary artery. Eight weeks after operation, appraisal on TCM syndrome
      revealed in the model was made from the aspects of general status, breathing
      frequency, heart rate, exhausting swimming time and electrocardiogram, and left
      ventricular structure and function were observed with echocardiography. RESULTS:
      Eight weeks after operation, as compared with those in the sham group, in the
      model group, the heart rate and breathing frequency were accelerated, the
      exhausting swimming time shortened, the echocardiogram parameters such as
      interventricular septum end-diastole thickness (IVSTd), posterior wall end
      diastole thickness (PWTd), posterior wall end-systolic thickness (PWTs), ejection
      fraction (EF) and fractional shortening (FS) of the left ventricular reduced (P <
      0.01), while left ventricular end-diastolic dimension (LVDd) and end-systolic
      dimension (LVDs) obviously increased (P < 0.01). In 12 leads electrocardiogram,
      the leads of ST segment elevated and abnormal Q wave increased. Additionally, the
      ratio of whole heart weight/body weight increased (P < 0.05). CONCLUSION: The HF
      rats after MI manifests Xin-qi deficiency and blood stasis syndrome, and shows
      the pathological changes of left ventricular remodeling and function impairment.

PMID- 17432684
TI  - [Comparative study on effects of three traditional Chinese medicinal compounds on
      energy metabolism related enzymes in cerebral tissue of rats after focal cerebral
      ischemia and reperfusion].
AB  - OBJECTIVE: To compare the effects of three traditional Chinese medicinal
      compounds on energy metabolism related enzymes in cerebral tissue of rats after
      focal cerebral ischemia and reperfusion (I/R). METHODS: The local cerebral I/R
      model was established by ligation of the middle cerebral arteries (MCA). The
      animals were divided into the sham-operative group, the model group, the Yiqi
      Huoxue Recipe (YHR) group, the Zhengan Xifeng Decoction (ZXD) group and the
      Xinglou Chengqi Decoction (XCD) group. The mitochondria in brain tissue was
      obtained by density-centrifugation and differential centrifugation, then the
      activities of succinate dehydrogenase (SDH), Na+ -K+ -ATPase, creatine kinase-BB
      (CK-BB) in homogenate of brain tissue were measured by chemical chromometry.
      RESULTS: Activities of SDH and Na+-K+ -ATPase were lower and that of CK-BB was
      higher in the model group than those in the sham -operative group at all time
      points after I/R (P< 0.01). Compared with those in the model group, activity of
      Na+ -K+ -ATPase was higher only in the ZXD group at 24 h after I/R, while at 48 h
      and 72 h after I/R, activities of both SDH and Na+ -K+ -ATPase were higher in all
      the treatment groups. As for the activity of CK-BB, it was lower in all the
      treatment groups (P < 0.05). The optimal effect was shown in the ZXD group at 24
      h, in the XCD group at 48 h, and in the YHR group at 72 h after I/R. CONCLUSION:
      The three traditional Chinese medicinal compounds could reduce pathologic injury
      after focal cerebral I/R in rats by promoting activity of SDH and Na+ -K+ -ATPase
      and inhibiting that of CK-BB, the optimal effect of ZXD was shown at 24 h after
      I/R, that of XCD at 48 h after I/R and of YHR at 72 h after I/R.

PMID- 17432685
TI  - [Establishment of oxygen and glucose deprive model of in vitro cultured
      hippocampal neuron and effect of ligustrazine on intracellular Ca+ level in model
      neurons].
AB  - OBJECTIVE: To establish the oxygen and glucose deprive (OGD) model in cultured
      hippocampal neuron and study the effect of ligustrazine on intracellular Ca2+
      level in the model neurons. METHODS: The OGD model was established in cultured
      hippocampal neuron, and the intracellular Ca2+ level in it was detected by laser
      scanning confocal microscope (LSCM). RESULTS: The OGD model was successfully
      established in cultured hippocampal neurons; the intracellular Ca2+ level in the
      OGD model group was significantly higher than that in the blank control group (P
      < 0.05), and that in the nemodipine and high and medium dosage of ligustrazine
      treated groups was lower than that in the OGD model group (P < 0.05). CONCLUSION:
      Intracellular Ca2+ overload occurs in OGD model neuron, which could be
      antagonized by ligustrazine, indicating that ligustrazine has a protective effect
      on hippocampal neuron from hypoxic-ischemic injury.

PMID- 17432686
TI  - [Study on effect of Xianzhong Injection on morphology of knee and insulin-like
      growth factor-1 in rabbits with early stage osteoarthritis].
AB  - OBJECTIVE: To investigate the effect of Xianzhong Injection (XI) on morphology of
      knee and insulin-like growth factor-1 (IGF-1) in rabbits with early stage
      osteoarthritis (OA). METHODS: One hundred and twenty rabbits were randomly
      divided into 5 groups, the blank group, the model group treated with 0.5 mL
      normal saline once a week, the positive control group treated with 0.5 mL
      hyaluronate once a week, and the XI 1 group and XI 2 group with 0.5 mL XI once
      and twice a week, respectively, all the medicines were medicated via intra
      articular injection. Knee joint function was examined 8 weeks after modeling, IGF
      1 content in serum and synovia was detected, and the histologic examination of
      articular cartilage was observed by Mallory staining as well. RESULTS: The
      improvement of knee joint function was better in the XI 1 and 2 groups than that
      in the model group (P < 0.01), and that in the XI 1 group was equivalent to that
      in the positive control group (P > 0.05). Histologic examination showed there was
      no calcification in all the layers of cartilage in the positive control group and
      the XI 1 group with complete cartilaginous bluish-green collagen preserved. The
      content of IGF-1 increased in synovia and serum in the positive control group and
      the two XI groups as compared with that in the model group (P < 0.05).
      CONCLUSION: XI can improve knee joint function to certain extent in early OA, and
      repair the degenerative cartilage.

PMID- 17432687
TI  - [Effect of clearing heat and removing dampness method on formation of pigment
      gallstones in rabbits].
AB  - OBJECTIVE: To observe dynamically the effect of drugs for clearing heat and
      removing dampness (CHRD) on biliary components in rabbits with pigment gallstones
      (PGS). METHODS: Forty rabbits were established into PGS model and randomly
      divided into 3 groups, the bacterial infection group, the CHRD low-dose group and
      the CHRD high-dose group. Besides, a normal group was set up with healthy rabbits
      for control. Changes of total bilirubin (TB), unconjugated bilirubin (UCB), total
      bile acid (TBA), Ca2+, bacterial and endogenous beta-glucuronidase (beta-Gase) in
      bile were observed. RESULTS: CHRD drugs significantly decreased the contents of
      UCB, Ca2+, bacterial and endogenous beta-Gase (P < 0.05), and increased TBA in
      bile (P < 0.05). CONCLUSION: CHRD drugs have good effect in reducing the
      lithogenesis of the pigment gallstones.

PMID- 17432688
TI  - [Experimental study on effect of Shenling Yigan Granule in antagonizing duck
      hepatitis B virus].
AB  - OBJECTIVE: To study the viral inhibitory effect of Shenling Yigan Granule (SYG)
      on duck hepatitis B virus (DHBV) in vivo. METHODS: Chongqing ducks infected with
      DHBV were used. They were randomly divided into five groups, the small-, medium-
      and high-dose (1.6 g/kg, 3.2 g/kg, 6.4 g g/kg) SYG groups, the lamivudine
      positive control group, and the model group. The changes of serum DHBV-DNA, DHB
      sAg contents and hepatic pathology were observed. RESULTS: The serum content of
      DHBV-DNA in the three SYG groups and the positive control group was significantly
      decreased (P < 0.05), while it was rebounded in the latter at day 7 after stopped
      lamivudine administration. The change of DHBsAg level was insignificantly in all
      groups. And the hepatic pathological change in the SYG groups and positive
      control group was slighter than that in the model control group, but showed
      insignificant difference in comparison between the SYG groups and the model group
      (P > 0.05). CONCLUSION: SYG has certain in vivo inhibitory effects on DHBV-DNA.

PMID- 17432689
TI  - [Clinical observation on effects of therapeutic method of expelling wind,
      eliminating phlegm and promoting blood circulation in treating acute cerebral
      infarction in stroke unit].
AB  - OBJECTIVE: To observe the effects of therapeutic method of expelling wind,
      eliminating phlegm and promoting blood circulation (EWEPPB) in treating acute
      cerebral infarction (ACI) depending on the clinical and data platform of stroke
      clinical unit. METHODS: ACI patients were randomly assigned to the control group
      (36 cases) treated by routine Western therapy alone and the treatment group (32
      cases) with routine therapy plus Chinese medicinal compound for EWEPPB. The
      treatment course was 14 days. The scores of TCM symptom, the NIH stroke scale
      (NIHSS), and Barthel index (BI) were used for evaluating the effect of treatment.
      RESULTS: The scores of TCM symptom and NIHSS decreased, and that of BI increased
      after treatment in both groups, and the treatment in the treatment group showed a
      effect significantly better than that in the control group (P < 0.05).
      CONCLUSION: EWEPPB is effective method in treating ACI, traditional Chinese
      compounds for EWEPPB could play a positive role in the stroke unit.

PMID- 17432690
TI  - [Clinical observation on effect of compound Shiwei Tablet in treating urinary
      tract infection].
AB  - OBJECTIVE: To evaluate the safety and efficacy of Compound Shiwei Tablet (CST) in
      treating upper and lower urinary tract infection (UTI, pyretic stranguria of
      dampness-heat of the Lower-jiao type in 'TCM). METHODS: A multi-center,
      randomized, and opened clinical trial was conducted in the UTI patients with
      Sanjin Tablet (ST) as the parallel positive control medicine. The comprehensive
      efficacy, effect on TCM syndrome score, and change of urinary leukocyte count
      were observed, and the adverse reaction was recorded. RESULTS: In the 147 upper
      UTI cases and the 312 lower UTI cases after treatment, the comprehensive effect
      was higher and urinary leukocyte was less in the CST treated patients than in the
      ST treated patients (P < 0.05); but significant difference in the improvement of
      TCM symptoms was found between them only in the lower UTI cases ( P < 0.05); and
      no adverse reaction was observed during the treatment course. CONCLUSION: CST has
      definite therapeutic efficacy on UTI and is safe in clinical application.

PMID- 17432691
TI  - [Clinical observation on treatment of chronic prostatitis syndrome type III B by
      Tiaoshen Tonglin Decoction].
AB  - OBJECTIVE: To observe the clinical effect of Tiaoshen Tonglin Decoction (TTD)) on
      chronic prostatitis syndrome (CPS) and its effects on urinary flow rate (UFR),
      uric acid (UA) content and pH value in expressed prostate secretions (EPS).
      METHODS: One hundred and eight patients with CPS were randomly assigned to two
      groups, the treatment group (56 cases) treated with TTI) and the control group
      (52 cases) with terazosin tablet, both for 60 days. The changes of chronic
      prostatitis symptom index (NIH-CPSL), established by the National Institutes of
      Health, U.S.A., UA and pH in EPS, as well as UFR were observed before and after
      treatment. RESULTS: The cure rate and the total effective rate in the treatment
      group were higher than those in the control group respectively (P < 0.05); after
      treatment, the UA level, pH value in EPS and NIH-CPSI decreased significantly in
      the treatment group (P < 0.01), lower than those in the control group, which had
      significant change (P < 0.05); the maximum UFR and average UFR of both groups
      were improved markedly after treatment (P < 0.05) with insignificant difference
      between the groups. CONCLUSION: TTD can improve the UFR, decrease the NIH-CPSI
      score, pH value and UA level in the EPS, is an effective recipe for treatment of
      CPS.

PMID- 17432692
TI  - [Clinical observation on treatment of radiation pneumonia by Qingjin Runfei
      Decoction combined with hormone and antibiotic].
AB  - OBJECTIVE: To observe the curative effect of Qingjin Runfei Decoction (QRD)
      combined with hormone and antibiotic in treating radiation pneumonia (RP).
      METHODS: Patients were randomly assigned to two groups, the control group (51
      cases) treated with hormone and antibiotic and the treated group (53 cases) with
      the above therapy plus QRD. The curative effects on RP, quality of life (QOL),
      chest radiography and TCM symptoms were observed. RESULTS: The curative effects
      on the above items in the treated group were all significantly better than those
      in the control group (P < 0.05). CONCLUSION: QRD could enhance the effects of
      hormone and antibiotic in treating RP, as well as improve QOL of the patients.

PMID- 17432693
TI  - [Effects of Ginkgo biloba extract (ginaton) on mRNA expression of bcl-2 and bcl
      xL in myocardium of patients underwent hypothermic cardiopulmonary bypass].
AB  - OBJECTIVE: To investigate the effects of Ginkgo biloba extract (Ginaton) on bcl-2
      and bcl-xL mRNA expression in the myocardium of patients underwent hypothermic
      cardiopulmonary bypass (CPB). METHODS: Thirty congenital heart disease patients
      were randomly assigned to 2 groups, the control group and the treated group.
      Patients in both groups received St. Thomas' cardioplegic solution via radix
      aortae, while Ginaton (0.5 mg/kg) was added in the treated group. Cardiac surgery
      was started after complete heart arrest. Myocardium was taken before the aorta
      ascendens was unblocked and mRNA expression of bcl-2 and bcl-xL in the
      ventricular tissue was detected by RT-PCR. RESULTS: The gene expressions of bcl-2
      and bcl-xL were significantly higher in the treated group than those in the
      control group (P < 0.05). CONCLUSION: Ginaton could promote the mRNA expressions
      of the antiapoptotic gene bcl-2 and bcl-xL in myocardium of patients underwent
      CI'PB.

PMID- 17432694
TI  - [Rethinking on application of "syndrome differentiation through formula effect
      assessment"].
AB  - By summarizing the state of application of "syndrome differentiation through
      formula effect assessment", it was pointed out that several problems exist in
      this kind of study, mainly the irrational setting of experimental control group,
      over simplified pharmacodynamic indexes, and negligence of study on
      "correspondence between drug and disease", etc. The authors proposed accordingly
      the thinking methods and strategy in the study on "syndrome differentiation
      through formula effect assessment" should be setting control properly, taken
      "correspondence between disease and syndrome" as the key point, and to define
      clearly the criteria for evaluating the efficacy of formula as the premise.

PMID- 17432695
TI  - [Application of computerized virtual screening technique in traditional Chinese
      medicine].
AB  - The rapid development of computer technology, molecular pharmacology and
      molecular biology extremely promoted the extensive and successful application of
      virtual screening technique (VST) in pharmaceutical exploitation. Based on
      plentiful literature and their own previous work, the authors elaborated the
      principles, methodology and strategy of VST systematically, gave a retrospection
      on the application of VST in the field of TCM in the last several years, and
      supposed that along with deepening of understanding, VST would play a greater
      role in TCM.

PMID- 17432696
TI  - [On establishment of vascular endothelial cell injury model of blood stasis
      syndrome based on integration of disease identification and syndrome
      differentiation].
AB  - To establish the vascular endothelial cell (VEC) injury model of blood stasis
      syndrome (BSS) based on integration of disease identification and syndrome
      differentiation is one of the aspects of the research on BSS model. This paper
      discussed the necessity and feasibility of the establishment of that model, and
      suggested that the model is of important academic value, far-reaching scientific
      research value and active clinic value.

PMID- 17432697
TI  - [Lexical gap and translation of traditional Chinese medical terms].
AB  - The phenomenon of lexical gap, a commonly encountered problem in cross-cultural
      communication, often causes trouble to translation in cross-cultural
      communication. The author analyzes the phenomenon of lexical gap in the English
      translation of traditional Chinese medical terms from the viewpoint of TCM
      culture, and puts forward the principles for their translation, that is,
      equivalence translation, equivalence in meaning translation and transliteration.

PMID- 17432698
TI  - [Progress of study on prevention and treatment of osteoporosis by compound
      Gushukang].
AB  - Gushukang is a compound Chinese herbal preparation. Pharmacological studies
      indicated that Gushukang can increase bone density, inhibit bone resorption,
      promote bone formation, and restore bone microstructure, as well as improve bone
      biomechanical parameters and promote healing of bone fracture. Clinical
      observations demonstrated that it has favorable efficacy in preventing and
      treating osteoporosis.

PMID- 17432699
TI  - Is there a role for hyperoxia in the management of severe traumatic brain injury?

PMID- 17432700
TI  - Effect of hyperoxia on cerebral metabolic rate for oxygen measured using positron
      emission tomography in patients with acute severe head injury.
AB  - OBJECT: Recent observations indicate that traumatic brain injury (TBI) may be
      associated with mitochondrial dysfunction. This, along with growing use of brain
      tissue PO2 monitors, has led to considerable interest in the potential use of
      ventilation with 100% oxygen to treat patients who have suffered a TBI. To date,
      the impact of normobaric hyperoxia has only been evaluated using indirect
      measures of its impact on brain metabolism. To determine if normobaric hyperoxia
      improves brain oxygen metabolism following acute TBI, the authors directly
      measured the cerebral metabolic rate for oxygen (CMRO2) with positron emission
      tomography before and after ventilation with 100% oxygen. METHODS: Baseline
      measurements of arterial and jugular venous blood gases, mean arterial blood
      pressure, intracranial pressure, cerebral blood flow (CBF), cerebral blood
      volume, oxygen extraction fraction, and CMRO2 were made at baseline while the
      patients underwent ventilation with a fraction of inspired oxygen (FiO2) of 0.3
      to 0.5. The FiO2 was then increased to 1.0, and 1 hour later all measurements
      were repeated. Five patients were studied a mean of 17.9 +/- 5.8 hours (range 12
      23 hours) after trauma. The median admission Glasgow Coma Scale score was 7
      (range 3-9). During ventilation with 100% oxygen, there was a marked rise in PaO2
      (from 117 +/- 31 to 371 +/- 99 mm Hg, p < 0.0001) and a small rise in arterial
      oxygen content (12.7 +/- 4.0 to 13.3 +/- 4.6 vol %, p = 0.03). There were no
      significant changes in systemic hemodynamic or other blood gas measurements. At
      the baseline evaluation, bihemispheric CBF was 39 +/- 12 ml/100 g/min and
      bihemispheric CMRO2 was 1.9 +/- 0.6 ml/ 100 g/min. During hyperoxia there was no
      significant change in either of these measurements. (Values are given as the mean
      +/- standard deviation throughout.) CONCLUSIONS: Normobaric hyperoxia did not
      improve brain oxygen metabolism. In the absence of outcome data from clinical
      trials, these preliminary data do not support the use of 100% oxygen in patients
      with acute TBI, although larger confirmatory studies are needed.

PMID- 17432701
TI  - Lack of utility of arteriojugular venous differences of lactate as a reliable
      indicator of increased brain anaerobic metabolism in traumatic brain injury.
AB  - OBJECT: Ischemic lesions are highly prevalent in patients with traumatic brain
      injuries (TBIs) and are the single most important cause of secondary brain
      damage. The prevention and early treatment of these lesions is the primary aim in
      the modem treatment of these patients. One of the most widely used monitoring
      techniques at the bedside is quantification of brain extracellular level of
      lactate by using arteriojugular venous differences of lactate (AVDL). The purpose
      of this study was to determine the sensitivity, specificity, and predictive value
      of AVDL as an indicator of increases in brain lactate production in patients with
      TBIs. METHODS: Arteriojugular venous differences of lactate were calculated every
      6 hours using samples obtained though a catheter placed in the jugular bulb in 45
      patients with diffuse head injuries (57.8%) or evacuated brain lesions (42.2%).
      Cerebral lactate concentration obtained with a 20-kD microdialysis catheter
      implanted in undamaged tissue was used as the de facto gold standard. Six hundred
      seventy-three AVDL determinations and cerebral microdialysis samples were
      obtained simultaneously; 543 microdialysis samples (81%) showed lactate values
      greater than 2 mmol/L, but only 21 AVDL determinations (3.1%) showed an increase
      in brain lactate. No correlation was found between AVDL and cerebral lactate
      concentration (p = 0.014, p = 0.719). Arteriojugular venous differences of
      lactate had a sensitivity and specificity of 3.3 and 97.7%, respectively, with a
      false-negative rate of 96.7% and a false-positive rate of 2.3%. CONCLUSIONS:
      Arteriojugular venous differences of lactate do not reliably reflect increased
      cerebral lactate production and consequently are not reliable in ruling out brain
      ischemia in patients with TBIs. The clinical use of this monitoring method in
      neurocritical care should be reconsidered.

PMID- 17432702
TI  - Sex and genetic associations with cerebrospinal fluid dopamine and metabolite
      production after severe traumatic brain injury.
AB  - OBJECT: Dopamine (DA) pathways have been implicated in cognitive deficits after
      traumatic brain injury (TBI). Both sex and the dopamine transporter (DAT) 3'
      variable number of tandem repeat polymorphism have been associated with
      differences in DAT protein density, and DAT protein affects both presynaptic DA
      release, through reverse transport, and DA reuptake. Catecholamines and
      associated metabolites are subject to autooxidation, resulting in the formation
      of reactive oxygen species that may contribute to subsequent oxidative injury.
      The purpose of this study was to determine associations between factors that
      affect DAT expression and cerebrospinal fluid (CSF) DA and metabolite levels
      after severe TBI. METHODS: Sixty-three patients with severe TBI (Glasgow Coma
      Scale score < or = 8) were evaluated. The patients' genotypes were obtained using
      previously banked samples of CSF, and serial CSF samples (416 samples) were used
      to evaluate DA and metabolite levels. High-performance liquid chromatography was
      used to determine CSF levels of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and
      homovanillic acid (HVA) during the first 5 days after injury. Mixed-effects
      multivariate regression modeling revealed that patients with the DAT 10/10
      genotype had higher CSF DA levels than patients with either the DAT 9/9 or DAT
      9/10 genotypes (p = 0.009). Females with the DAT 10/10 genotype had higher CSF DA
      levels than females with the DAT 9/9 or DAT 9/10 genotypes, and sex was
      associated with higher DOPAC levels (p = 0.004). Inotrope administration also
      contributed to higher DA levels (p = 0.002). CONCLUSIONS: In addition to systemic
      administration of DA, inherent factors such as sex and DAT genotype affect post
      TBI CSF DA and DA metabolite levels, a phenomenon that may modulate
      susceptibility to DA-mediated oxidative injury.

PMID- 17432703
TI  - Is intracranial pressure monitoring in the epidural space reliable? Fact and
      fiction.
AB  - OBJECT: Epidural pressures have been reported as being systematically higher than
      ventricular fluid pressures. These discrepancies have been attributed both to the
      characteristics of the sensor and to the particular anatomy of the epidural
      space. To determine which of these two possible causes better explains higher
      epidural readings, the authors compared pressure values obtained during
      simultaneous epidural and lumbar pressure monitoring in 53 patients and during
      simultaneous subdural and lumbar pressure monitoring in 22 patients. The same
      nonfluid coupled sensor device was used in all compartments. METHODS: All 75
      patients had normal craniospinal communication. Simultaneous intracranial and
      lumbar readings were performed every 30 seconds. The epidural-lumbar and subdural
      lumbar pressure values were compared using correlation analysis and the Bland
      Altman method. The median differences in initial epidural-lumbar and subdural
      lumbar pressure values were 11 mm Hg (interquartile range 2-24 mm Hg) and 0 mm Hg
      (interquartile range -2 to 1 mm Hg), respectively. The correlation coefficients
      of the mean epidural-lumbar and subdural-lumbar intracranial pressure (ICP)
      values were p = 0.48 (p < 0.001) and p = 0.88 (p < 0.001), respectively. Using
      the Bland-Altman analysis, epidural-lumbar methods showed a mean difference of 
      20.93 mm Hg; epidural pressure values were systematically higher than lumbar
      values, and these discrepancies were greater with higher ICP values. Subdural
      lumbar methods showed a mean difference of 0.35 mm Hg and both were equally valid
      with all mean ICP values. CONCLUSIONS: Epidural ICP monitoring produces
      artifactually high values. These values are not related to the type of sensor
      used but to the specific characteristics of the epidural intracranial space.

PMID- 17432704
TI  - Evaluation of intraaxial enhancing brain tumors on magnetic resonance imaging:
      intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate
      dimeglumine for visualization and assessment, and implications for surgical
      intervention.
AB  - OBJECT: The goal in this article was to compare 0.1 mmol/kg doses of gadobenate
      dimeglumine (Gd-BOPTA) and gadopentetate dimeglumine, also known as gadolinium
      diethylenetriamine pentaacetic acid (Gd-DTPA), for enhanced magnetic resonance
      (MR) imaging of intraaxial brain tumors. METHODS: Eighty-four patients with
      either intraaxial glioma (47 patients) or metastasis (37 patients) underwent two
      MR imaging examinations at 1.5 tesla, one with Gd-BOPTA as the contrast agent and
      the other with Gd-DTPA. The interval between fully randomized contrast medium
      administrations was 2 to 7 days. The T1-weighted spin echo and T2-weighted fast
      spin echo images were acquired before administration of contrast agents and T1
      weighted spin echo images were obtained after the agents were administered.
      Acquisition parameters and postinjection acquisition times were identical for the
      two examinations in each patient. Three experienced readers working in a fully
      blinded fashion independently evaluated all images for degree and quality of
      available information (lesion contrast enhancement, lesion border delineation,
      definition of disease extent, visualization of the lesion's internal structures,
      global diagnostic preference) and quantitative enhancement (that is, the extent
      of lesion enhancement after contrast agent administration compared with that seen
      before its administration [hereafter referred to as percent enhancement],
      lesion/brain ratio, and contrast/noise ratio). Differences were tested with the
      Wilcoxon signed-rank test. Reader agreement was assessed using kappa statistics.
      Significantly better diagnostic information/imaging performance (p < 0.0001, all
      readers) was obtained with Gd-BOPTA for all visualization end points. Global
      preference for images obtained with Gd-BOPTA was expressed for 42 (50%), 52
      (61.9%), and 56 (66.7%) of 84 patients (readers 1, 2, and 3, respectively)
      compared with images obtained with Gd-DTPA contrast in four (4.8%), six (7.1%),
      and three (3.6%) of 84 patients. Similar differences were noted for all other
      visualization end points. Significantly greater quantitative contrast enhancement
      (p < 0.04) was noted after administration of Gd-BOPTA. Reader agreement was good
      (kappa > 0.4). CONCLUSIONS: Lesion visualization, delineation, definition, and
      contrast enhancement are significantly better after administration of 0.1 mmol/kg
      Gd-BOPTA, potentially allowing better surgical planning and follow up and
      improved disease management.

PMID- 17432705
TI  - Treatment for posterior fossa dissemination of primary supratentorial glioma.
AB  - OBJECT: This study was designed to assess the presentation, management, and
      outcome of cases involving patients who had a supratentorial glioma that
      subsequently progressed in the posterior fossa (PF). METHODS: The authors
      performed a retrospective chart review of adult patients treated between 1997 and
      2005 for supratentorial gliomas that progressed in the PF. The 29 patients with
      PF progression in this study were relatively young (median age of 34 years at
      original presentation). Twenty of these patients presented with symptoms. The
      symptoms were typically nonspecific to this population, at times leading to
      delays in diagnosis. Overall, these symptoms resolved in eight patients (40%) and
      progressed or remained unchanged in 12 (60%). Patients treated with more than
      5000 cGy of radiation administered to the PF were more likely to have symptom
      resolution than those who received any other form of treatment, including reduced
      doses of radiation (p = 0.004). The patients treated with higher doses also
      survived significantly longer after PF progression (univariate analysis, p =
      0.01, and after adjusting for tumor grade, p = 0.04). CONCLUSIONS: Patients with
      PF progression of supratentorial infiltrative gliomas may benefit from treatment,
      and the authors recommend more than 5000 cGy of radiation to the PF if prior
      radiotherapy ports and doses allow.

PMID- 17432706
TI  - Prognostic significance of surgery and radiation therapy in cases of anaplastic
      astrocytoma: retrospective analysis of 170 cases.
AB  - OBJECT: The purpose of this retrospective study was to estimate the prognostic
      impact of treatment parameters for 170 patients with anaplastic astrocytoma (AA).
      METHODS: Survival outcome and prognostic factors were analyzed for 170 patients
      with AA. In the multivariate analysis, site of lesion (frontal or parietal lobe,
      p = 0.002), extent of surgery (total or subtotal resection, p = 0.001), Karnofsky
      Performance Scale status (0-2, p = 0.021), age (< or = 50 years, p = 0.024), and
      total dose of radiation therapy (> 60 Gy, p = 0.029) were significant favorable
      prognostic factors. In the analysis of groups according to extent of surgery,
      patients who underwent total or subtotal resection had a significantly more
      favorable prognosis than did patients who underwent partial resection or biopsy
      (5-year survival rate 54.0% for total or subtotal resection compared with 17.5%
      for partial resection or biopsy; median survival time [MST] 62.6 months compared
      with 22.9 months [p < 0.0001, log-rank test]; hazard ratio [HR] 0.67; and 95%
      confidence interval [CI] 0.52-0.85 [p = 0.001]). In the analysis of groups
      according to total radiation dose, the group of patients who received doses
      greater than 60 Gy had a significantly more favorable prognosis than did the
      group who received 60 Gy or less (5-year survival rate 45.0% for patients who
      received doses greater than 60 Gy compared with 21.1% for those receiving 60 Gy
      or less; MST 48.9 months compared with 21.6 months [p = 0.0006, log-rank test];
      HR 0.96; 95% CI 0.93-0.99 [p = 0.029]). CONCLUSIONS: The most important parameter
      in the treatment of AA was extent of surgery, and total radiation dose was the
      second most important factor. Resection of as much of the tumor as possible and
      delivery of a total radiation dose of greater than 60 Gy seem to be required for
      local control of AA.

PMID- 17432707
TI  - Motor tract monitoring during insular glioma surgery.
AB  - OBJECT: Surgery for insular gliomas incurs a considerable risk of motor
      morbidity. In this study the authors explore the validity and utility of
      continuous motor tract monitoring to detect and reverse impending motor
      impairment during insular glioma resection. METHODS: Motor evoked potentials
      (MEPs) were successfully monitored during 73 operations to remove insular
      gliomas. Seventy-two cases were assessable, and one patient died during the early
      postoperative course. In this prospective observational approach, MEP monitoring
      results were correlated with intraoperative events and perioperative clinical
      data. Intraoperative recordings of MEPs remained stable in 40 cases (56%),
      indicating unimpaired motor outcome and allowing safe completion of the hazardous
      steps of the procedure. Deterioration of MEPs occurred in 32 cases (44%). This
      deterioration was reversible after intervention in 21 cases (29%), and there was
      no new motor deficit except for transient paresis in nine of these cases (13%).
      Surgical measures could not prevent irreversible MEP deterioration in 11 cases
      (15%). Transient mild or moderate paresis occurred if complete MEP loss was
      avoided. Irreversible MEP loss in seven cases (10%) occurred after completion of
      resection in four of these seven cases, and was consistently an indicator of both
      a stroke within the deep motor pathways and permanent paresis, which remained
      severely disabling in three patients (4%). In contrast, permanently severe
      paresis occurred in two (18%) of 11 cases without useful MEP monitoring.
      CONCLUSIONS: Continuous MEP monitoring is a valid indicator of motor pathway
      function during insular glioma surgery. This method indicates that remote
      ischemia, in this study the leading cause of impending motor deterioration, helps
      to avert definitive stroke of the motor pathways and permanent new paresis in the
      majority of cases. The rate of permanently severe new deficit appears to be
      greater in unmonitored cases.

PMID- 17432708
TI  - Clinical impact of integrated functional neuronavigation and subcortical
      electrical stimulation to preserve motor function during resection of brain
      tumors.
AB  - OBJECT: The authors evaluated the clinical impact of combining functional
      neuronavigation with subcortical electrical stimulation to preserve motor
      function following the removal of brain tumors. METHODS: Forty patients underwent
      surgery for treatment of brain tumors located near pyramidal tracts that had been
      identified by fiber tracking. The distances between the electrically stimulated
      white matter and the pyramidal tracts were measured intraoperatively with
      tractography-integrated functional neuronavigation, and correlated with
      subcortical motor evoked potentials (MEPs) and clinical symptoms during and after
      resection of the tumors. Motor function was preserved after appropriate tumor
      resection in all cases. In 18 of 20 patients, MEPs were elicited from the
      subcortex within 1 cm of the pyramidal tracts as measured using intraoperative
      neuronavigation. During resection, improvement of motor weakness was observed in
      two patients, whereas transient mild motor weakness occurred in two other
      patients. In 20 patients, the distances between the stimulated subcortex and the
      estimated pyramidal tracts were more than I cm, and MEPs were detected in only
      three of these patients following stimulation. CONCLUSIONS: Intraoperative
      functional neuronavigation and subcortical electrical stimulation are
      complementary techniques that may facilitate the preservation of pyramidal tracts
      around 1 cm of resected tumors.

PMID- 17432709
TI  - Gliomas and venous thromboembolism: how common?

PMID- 17432710
TI  - Epidemiology of venous thromboembolism in 9489 patients with malignant glioma.
AB  - OBJECT: The authors sought to define the incidence of symptomatic venous
      thromboembolism (VTE) in patients harboring malignant gliomas. METHODS: The
      authors conducted a retrospective analysis of data obtained in all cases of
      malignant glioma diagnosed in California during a 6-year period; the occurrence
      of a VTE was identified using linked hospital discharge data. The Cox
      proportional hazard model was used to analyze the association of specific risk
      factors with the development of a VTE or death within 2 years of the cancer
      diagnosis. Among 9489 cases, the 2-year cumulative incidence of VTE was 7.5% (715
      cases), with a rate of 16.1 events per 100 person-years during the first 6
      months. Three hundred ninety-one (55%) of these 715 cases were diagnosed within
      61 days of major neurosurgery. Risk factors for VTE included older age (hazard
      ratio [HR] 2.6, confidence interval [CI] 2.0-3.4 for age range 65-74 years
      compared with < or = 45 years), glioblastoma multiforme histology (HR 1.7, CI 1.4
      2.1), three or more chronic comorbidities (HR 3.5, CI 2.8-4.3 [compared with no
      comorbidity]), and neurosurgery within 61 days (HR 1.7, CI 1.3-2.3). Patients in
      whom a VTE was present were at higher risk of dying within 2 years (HR 1.3, CI
      1.2-1.4). In a nested case-control analysis of all VTE cases, there was no
      association between insertion of a vena cava filter and the risk of a recurrent
      VTE. CONCLUSIONS: In patients harboring a glioma there was a very high incidence
      of symptomatic VTEs, particularly within 2 months of neurosurgery. The
      development of a VTE was associated with a 30% increase in the risk of death
      within 2 years. Further studies are needed to determine if risk stratification
      and the use of medical prophylaxis after neurosurgery improves outcomes.

PMID- 17432711
TI  - Increase in glutamate as a sensitive indicator of extracellular matrix integrity
      in peritumoral edema: a 3.0-tesla proton magnetic resonance spectroscopy study.
AB  - OBJECT: The authors of previous studies based on diffusion tensor imaging have
      indicated that there are two types of peritumoral edema-namely, edema with
      preserved structural integrity of the glial matrix and edema with compromised
      glial matrix. The authors of this study hypothesized that functionality of the
      glutamate (Glu)-glutamine shuttle, a vital neuron-glia interaction, may be
      differentially affected by peritumoral edema. They tested this hypothesis using
      proton magnetic resonance (MR) spectroscopy on a 3.0-tesla system that is capable
      of quantifying Glu without need of editing. METHODS: Twenty-three patients, each
      with a single brain tumor mass and peritumoral edema (nine high-grade gliomas,
      eight metastatic brain tumors, and six meningiomas), and nine healthy individuals
      participated in this study. Single-voxel proton MR imaging targeting the region
      of peritumoral edema was performed using a 3.0-tesla system. Glutamate levels in
      the peritumoral edema of nonglial tumors was significantly elevated (p < 0.01)
      compared with edema associated with glial tumors or normal white matter. The
      finding confirmed that peritumoral edema in nonglial tumors is distinct from that
      of glial tumors, as previously indicated in diffusion tensor imaging studies. The
      authors hypothesized that the former condition represents a compensatory increase
      in activities of the Glu-glutamine shuttle brought about by simple expansion of
      the extracellular space due to edema. CONCLUSIONS: The assessment of Glu
      concentrations in peritumoral edema using 3.0-tesla proton MR spectroscopy may be
      developed into an objective index of the structural integrity of the glial
      matrix.

PMID- 17432712
TI  - Unilateral intraputamenal glial cell line-derived neurotrophic factor in patients
      with Parkinson disease: response to 1 year of treatment and 1 year of withdrawal.
AB  - OBJECT: Glial cell line-derived neurotrophic factor (GDNF) infused unilaterally
      into the putamen for 6 months has been previously shown to improve significantly
      motor functions and quality of life measures in 10 patients with Parkinson
      disease (PD) in a Phase I trial. In the present study the authors report the
      safety and efficacy of continuous treatment for a minimum of 1 year. After the
      trial was halted by the drug sponsor, the patients were monitored for an
      additional 1 year during which the effects of drug withdrawal were evaluated.
      METHODS: During the extended study period, patients received a 30-microg/day
      unilateral intraputamenal infusion of GDNF at a basal infusion rate supplemented
      with pulsed boluses every 6 hours at a convection-enhanced delivery rate to
      increase tissue penetration of the protein. When the study was stopped, the
      delivery system was reprogrammed to deliver sterile saline at the basal infusion
      rate of 2 microl/hour. The Unified Parkinson's Disease Rating Scale (UPDRS) total
      scores after 1 year of therapy were improved by 42 and 38% in the off- and on
      medication states; the motor UPDRS scores were also improved 45 and 39%,
      respectively. Benefits from treatment were lost by 9 to 12 months after the
      cessation of GDNF infusion. The UPDRS scores returned to their baseline and the
      patients required higher levels of conventional antiparkinsonian drugs to treat
      symptoms. After 11 months of treatment, the delivery system had to be removed in
      one patient because of risk of infection. Seven patients developed antibodies to
      GDNF but without evident clinical sequelae. There was no evidence for GDNF
      induced cerebellar toxicity, as evaluated by magnetic resonance imaging and
      clinical testing. CONCLUSIONS: The unilateral administration of GDNF results in
      significant, sustained bilateral benefits in patients with PD. These improvements
      are lost within 9 months of drug withdrawal. Safety concerns with GDNF therapy
      can be closely monitored and managed.

PMID- 17432713
TI  - Short-term and long-term safety of deep brain stimulation in the treatment of
      movement disorders.
AB  - OBJECT: The object of this study was to assess the long-term safety of deep brain
      stimulation (DBS) in a large population of patients with a variety of movement
      disorders. METHODS: All patients treated with DBS at the authors' center between
      1995 and 2005 were assessed for intraoperative, perioperative, and long-term
      adverse events (AEs). A total of 319 patients underwent DBS device implantation.
      Of these 319, 182 suffered from medically refractory Parkinson disease; the other
      patients had essential tremor (112 patients), dystonia (19 patients), and other
      hyperkinetic movement disorders (six patients). Intraoperative AEs were rare and
      included vasovagal response in eight patients (2.5%), syncope in four (1.2%),
      severe cough in three (0.9%), transient ischemic attack in one (0.3%), arrhythmia
      in one (0.3%), and confusion in one (0.3%). Perioperative AEs included headache
      in 48 patients (15.0%), confusion in 16 (5.0%), and hallucinations in nine
      (2.8%). Serious intraoperative/perioperative AEs included isolated seizure in
      four patients (1.2%), intracerebral hemorrhage in two patients (0.6%),
      intraventricular hemorrhage in two patients (0.6%), and a large subdural hematoma
      in one patient (0.3%). Persistent long-term complications of DBS surgery included
      dysarthria (4.0%), worsening gait (3.8%), cognitive dysfunction (4.0%), and
      infection (4.4%). Revisions were completed in 25 patients (7.8%) for the
      following reasons: loss of effect, lack of efficacy, infection, lead fracture,
      and lead migration. Hardware-related complications included 12 lead fractures and
      10 lead migrations. CONCLUSIONS: The authors conclude that in their 10-year
      experience, DBS has proven to be safe for the treatment of medically refractory
      movement disorders.

PMID- 17432714
TI  - Unilateral deep brain stimulation of the subthalamic nucleus for Parkinson
      disease.
AB  - OBJECT: The object of this study was to assess the results of unilateral deep
      brain stimulation (DBS) of the subthalamic nucleus (STN) for management of
      advanced Parkinson disease (PD). METHODS: A clinical series of 24 patients (mean
      age 71 years, range 56-80 years) with medically intractable PD, who were
      undergoing unilateral magnetic resonance imaging-targeted, electrophysiologically
      guided STN DBS, completed a battery of qualitative and quantitative outcome
      measures preoperatively (baseline) and postoperatively, using a modified Core
      Assessment Program for Intracerebral Transplantations protocol. The mean follow
      up period was 9 months. Statistically significant improvement was observed in the
      Unified Parkinson's Disease Rating Scale (UPDRS) Part II score (18%), the total
      UPDRS PART III score (31%), the contralateral UPDRS Part III score (63%), and
      scores for axial motor features (19%), contralateral tremor (88%), rigidity
      (60%), bradykinesia (54%), and dyskinesia (69%), as well as the Parkinson's
      Disease Quality of Life questionnaire score (15%) in the on-stimulation state
      compared with baseline. Ipsilateral symptoms improved by approximately 15% or
      less. Performance on the Purdue pegboard test improved in the contralateral hand
      in the on-stimulation state compared with the off-stimulation state (38%, p <
      0.05). The daily levodopa-equivalent dose was reduced by 21% (p = 0.018).
      Neuropsychological tests revealed an improvement in mental flexibility and a
      trend toward reduced letter fluency. There were no permanent surgical
      complications. Of the 16 participants with symmetrical disease, five required
      implantation of the DBS unit on the second side. CONCLUSIONS: Unilateral STN DBS
      is an effective and safe treatment for selected patients with advanced PD.
      Unilateral STN DBS provides improvement of contralateral motor symptoms of PD as
      well as quality of life, reduces requirements for medication, and possibly
      enhances mental flexibility. This method of surgical treatment may be associated
      with a reduced risk and may provide an alternative to bilateral STN DBS for PD,
      especially in older patients or patients with asymmetry of parkinsonism.

PMID- 17432715
TI  - Association between fluorine-18-labeled fluorodeoxyglucose uptake and 1p and 19q
      loss of heterozygosity in World Health Organization Grade II gliomas.
AB  - OBJECT: Oligodendroglial tumors harboring combined 1p and 19q loss (1p/19q LOH)
      are characterized by a favorable prognosis and response to chemotherapy and
      radiotherapy, but detection of 1p/19q LOH relies on postoperative procedures. The
      authors investigated the potential of fluorine-18-labeled fluorodeoxyglucose
      (FDG) uptake in positron emission tomography (PET) to predict 1p/19q LOH
      preoperatively in tumors whose appearance on initial magnetic resonance images
      was consistent with that of low-grade glioma. METHODS: The study population
      comprised 25 patients who had undergone preoperative FDG-PET followed by tumor
      resection. Neuronavigation ensured a precise match of FDG uptake with the site of
      biopsy. All tumor specimens were graded according to the World Health
      Organization (WHO) classification system. Microsatellite analysis was used to
      identify 1p/19q LOH. In this series, 16 of 25 gliomas corresponded to WHO Grade
      II. In eight of these 16, 1p/19q LOH was detected. Raised glucose utilization
      within the tumor was seen in the six of eight WHO Grade II gliomas with 1p/19q
      LOH and in none of the WHO Grade II gliomas without this genetic alteration (p =
      0.003). CONCLUSIONS: These findings demonstrate the potential of FDG-PET to
      predict 1p/19q LOH in WHO Grade II gliomas.

PMID- 17432716
TI  - Antitumor effects of vaccination with dendritic cells transfected with modified
      receptor for hyaluronan-mediated motility mRNA in a mouse glioma model.
AB  - OBJECT: The receptor for hyaluronan-mediated motility (RHAMM) is frequently
      overexpressed in brain tumors and was recently identified as an immunogenic
      antigen by using serological screening of cDNA expression libraries. In this
      study, which was conducted using a mouse glioma model, the authors tested the
      hypothesis that vaccination with dendritic cells transfected with RHAMM mRNA
      induces strong immunological antitumor effects. METHODS: The authors constructed
      a plasmid for transduction of the mRNAs transcribed in vitro into dendritic
      cells, which were then used to transport the intracellular protein RHAMM
      efficiently into major histocompatibility complex class II compartments by adding
      a late endosomal-lysosomal sorting signal to the RHAMM gene. The dendritic cells
      transfected with this RHAMM mRNA were injected intraperitoneally into the mouse
      glioma model 3 and 10 days after tumor cell implantation. The antitumor effects
      of the vaccine were estimated by the survival rate, histological analysis, and
      immunohistochemical findings for immune cells. Mice in the group treated by
      vaccination therapy with dendritic cells transfected with RHAMM mRNA survived
      significantly longer than those in the control groups. Immunohistochemical
      analysis revealed that greater numbers of T lymphocytes containing T cells
      activated by CD4+, CD8+, and CD25+ were found in the group vaccinated with
      dendritic cells transfected with RHAMM mRNA. CONCLUSIONS: These results
      demonstrate the therapeutic potential of vaccination with dendritic cells
      transfected with RHAMM mRNA for the treatment of malignant glioma.

PMID- 17432717
TI  - Enhanced proapoptotic effects of tumor necrosis factor-related apoptosis-inducing
      ligand on temozolomide-resistant glioma cells.
AB  - OBJECT: Death receptor targeting is an attractive approach in experimental
      treatment for tumors such as malignant gliomas, which are resistant to radiation
      and chemotherapy. Among the family of cytokines referred to as death li gands,
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has attracted
      clinical interest. The aim of this study was to assess whether TRAIL can be used
      as an adjuvant to temozolomide (TMZ) for apoptosis induction in malignant glioma
      cell lines. METHODS: Six human malignant glioma cell lines (A172, U87, U251, T98,
      U343, and U373) were exposed to human (h)TRAIL, TMZ, or an hTRAIL/TMZ combined
      treatment. Cell viability was assayed using 3-(4,5-dimethylthiazole-2-yl)-2,5
      diphenyltetrazolium bromide and phase-contrast microscopy. Cell apoptosis was
      detected using the terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick-end labeling technique and quantified using flow cytometric
      analysis. The apoptosis signaling cascade was studied with Western blotting. The
      additive effects of hTRAIL and TMZ resulted in a significant decrease in cell
      viability and an increased apoptotic rate. Expression of the death receptors DR5
      and DR4 in two cell lines (A172 and U251) upregulated significantly when they
      were used in combination hTRAIL/TMZ treatment (p < 0.05 compared with baseline
      control), leading to activation of caspase-8 and caspase-3 (p < 0.05 compared
      with baseline control) and confirming an extrinsic apoptotic pathway. A cell
      intrinsic pathway through mitochondrial cytochrome c was not activated.
      CONCLUSIONS: Based on this work, one may infer that hTRAIL should be considered
      as an adjuvant treatment for TMZ-resistant human malignant gliomas.

PMID- 17432718
TI  - Orthotopic transplantation of v-src-expressing glioma cell lines into
      immunocompetent mice: establishment of a new transplantable in vivo model for
      malignant glioma.
AB  - OBJECT: The aim of this study was to develop and characterize a new orthotopic,
      syngeneic, transplantable mouse brain tumor model by using the cell lines Tu-9648
      and Tu-2449, which were previously isolated from tumors that arose spontaneously
      in glial fibrillary acidic protein (GFAP)-v-src transgenic mice. METHODS:
      Striatal implantation of a 1-microl suspension of 5000 to 10,000 cells from
      either clone into syngeneic B6C3F1 mice resulted in tumors that were
      histologically identified as malignant gliomas. Prior subcutaneous inoculations
      with irradiated autologous cells inhibited the otherwise robust development of a
      microscopically infiltrating malignant glioma. Untreated mice with implanted
      tumor cells were killed 12 days later, when the resultant gliomas were several
      millimeters in diameter. Immunohistochemically, the gliomas displayed both the
      astroglial marker GFAP and the oncogenic form of signal transducer and activator
      of transcription-3 (Stat3). This form is called tyrosine-705 phosphorylated
      Stat3, and is found in many malignant entities, including human gliomas.
      Phosphorylated Stat3 was particularly prominent, not only in the nucleus but also
      in the plasma membrane of peripherally infiltrating glioma cells, reflecting
      persistent overactivation of the Janus kinase/Stat3 signal transduction pathway.
      The Tu-2449 cells exhibited three non-random structural chromosomal aberrations,
      including a deletion of the long arm of chromosome 2 and an apparently balanced
      translocation between chromosomes 1 and 3. The GFAP-v-src transgene was mapped to
      the pericentromeric region of chromosome 18. CONCLUSIONS: The high rate of
      engraftment, the similarity to the high-grade malignant glioma of origin, and the
      rapid, locally invasive growth of these tumors should make this murine model
      useful in testing novel therapies for human malignant gliomas.

PMID- 17432719
TI  - Correlation of magnetic resonance spectroscopic and growth characteristics within
      Grades II and III gliomas.
AB  - OBJECT: The accurate diagnosis of World Health Organization Grades II and III
      gliomas is crucial for the effective treatment of patients with such lesions.
      Increased cell density and mitotic activity are histological features that
      distinguish Grade III from Grade II gliomas. Because increased cellular
      proliferation and density both contribute to the in vivo magnetic resonance (MR)
      spectroscopic peak corresponding to choline-containing compounds (Cho), the
      authors hypothesized that multivoxel MR spectroscopy might help identify the
      tumor regions with the most aggressive growth characteristics, which would be
      optimal locations for biopsy. They investigated the ability to use one or more MR
      spectroscopic parameters to predict the MIB-1 cell proliferation index (PI), the
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end
      labeling cell death index (DI), the cell density, and the ratio of proliferation
      to cell death (PI/DI) within different regions of the same tumor. METHODS:
      Patients with presumed Grades II or III glioma underwent 3D MR spectroscopic
      imaging prior to surgery, and two or three regions within the tumor were targeted
      for biopsy retrieval based on their spectroscopic features. Biopsy specimens were
      extracted from the tumor during image-guided resection, and the PI, DI, and cell
      density were assessed in the specimens using immunohistochemical methods.
      CONCLUSIONS: The authors found that the relative levels of Cho and N
      acetylaspartate (NAA) correlated with the cell density, PI, and PI/DI ratio
      within different regions of the same tumor and that the association held for the
      subpopulation of nonenhancing tumors. The association was stronger in tumors with
      large ranges of Cho/NAA values, irrespective of the presence of contrast
      enhancement. The findings demonstrate the validity of using MR spectroscopy to
      identify regions of aggressive growth in presumed Grade II or III gliomas that
      would be suitable targets for retrieving diagnostic biopsy specimens.

PMID- 17432720
TI  - Pressure-dependent effect of shock waves on rat brain: induction of neuronal
      apoptosis mediated by a caspase-dependent pathway.
AB  - OBJECT: Shock waves have been experimentally applied to various neurosurgical
      treatments including fragmentation of cerebral emboli, perforation of cyst walls
      or tissue, and delivery of drugs into cells. Nevertheless, the application of
      shock waves to clinical neurosurgery remains challenging because the threshold
      for shock wave-induced brain injury has not been determined. The authors
      investigated the pressure-dependent effect of shock waves on histological changes
      of rat brain, focusing especially on apoptosis. METHODS: Adult male rats were
      exposed to a single shot of shock waves (produced by silver azide explosion) at
      overpressures of 1 or 10 MPa after craniotomy. Histological changes were
      evaluated sequentially by H & E staining and terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL). The
      expression of active caspase-3 and the effect of the nonselective caspase
      inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) were
      examined to evaluate the contribution of a caspase-dependent pathway to shock
      wave-induced brain injury. High-overpressure (> 10 MPa) shock wave exposure
      resulted in contusional hemorrhage associated with a significant increase in
      TUNEL-positive neurons exhibiting chromatin condensation, nuclear segmentation,
      and apoptotic bodies. The maximum increase was seen at 24 hours after shock wave
      application. Low-overpressure (1 MPa) shock wave exposure resulted in spindle
      shaped changes in neurons and elongation of nuclei without marked neuronal
      injury. The administration of Z-VAD-FMK significantly reduced the number of TUNEL
      positive cells observed 24 hours after high-overpressure shock wave exposure (p <
      0.01). A significant increase in the cytosolic expression of active caspase-3 was
      evident 24 hours after high-overpressure shock wave application; this increase
      was prevented by Z-VAD-FMK administration. Double immunofluorescence staining
      showed that TUNEL-positive cells were exclusively neurons. CONCLUSIONS: The
      threshold for shock wave-induced brain injury is speculated to be under 1 MPa, a
      level that is lower than the threshold for other organs. High-overpressure shock
      wave exposure results in brain injury, including neuronal apoptosis mediated by a
      caspase-dependent pathway. This is the first report in which the pressure
      dependent effect of shock wave on the histological characteristics of brain
      tissue is demonstrated.

PMID- 17432721
TI  - The nerve to the mylohyoid as a donor for facial nerve reanimation procedures: a
      cadaveric feasibility study.
AB  - OBJECT: Facial nerve injury with resultant facial muscle paralysis is disfiguring
      and disabling. Reanimation of the facial nerve has been performed using different
      regional nerves. The nerve to the mylohyoid has not been previously explored as a
      donor nerve for facial nerve reanimation procedures. METHODS: Five fresh adult
      human cadavers (10 sides) were dissected to identify an additional nerve donor
      candidate for facial nerve neurotization. Using a curvilinear cervicofacial skin
      incision, the nerve to the mylohyoid and facial nerve were identified. The nerve
      to the mylohyoid was transected at its point of entrance into the anterior belly
      of the digastric muscle. Measurements were made of the length and diameter of the
      nerve to the mylohyoid, and this nerve was repositioned superiorly to the various
      temporofacial and cervicofacial parts of the extracranial branches of the facial
      nerve. All specimens had a nerve to the mylohyoid. The mean length of this nerve
      available inferior to the mandible was 5.5 cm and the mean diameter was 1 mm. In
      all specimens, the nerve to the mylohyoid reached the facial nerve stem and the
      temporofacial and cervicofacial trunks without tension. No gross evidence of
      injury to surrounding neurovascular structures was identified. CONCLUSIONS: To
      the authors' knowledge, the use of the nerve to the mylohyoid for facial nerve
      reanimation has not been explored previously. Based on the results of this
      cadaveric study, the use of the nerve to the mylohyoid may be considered for
      facial nerve reanimation procedures.

PMID- 17432722
TI  - Inhibition of Src tyrosine kinase and effect on outcomes in a new in vivo model
      of surgically induced brain injury.
AB  - OBJECT: Brain tissue at the periphery of a neurosurgical resection site is
      vulnerable to injury by a variety of mechanisms including direct trauma, edema,
      hemorrhage, retractor stretch, and electrocautery. The goal in the present study
      was to develop an in vivo model of surgically induced brain injury and to test an
      Src tyrosine kinase inhibitor for neuroprotective properties in this model.
      METHODS: The authors developed a new surgically induced brain injury model in
      rats. This model involves resection of part of the frontal lobe. Sprague-Dawley
      male rats weighing between 300 and 350 g were divided randomly into four groups:
      Group 1, surgical injury with vehicle treatment; Group 2, surgical injury after
      treatment with PP1 (an Src tyrosine kinase inhibitor with known neuroprotective
      properties); Group 3, sham surgery; and Group 4, control. Postoperative
      assessment included blood-brain barrier (BBB) permeability studies, and
      histological, immunohistochemical, and Western blot analyses. The authors found
      that surgical injury caused localized edema and disruption of the BBB compared
      with findings in the sham surgery group. Treatment with PP1 was associated with
      decreased edema, decreased breakdown of the BBB, decreased expression of both
      vascular endothelial growth factor and phosphorylated extracellular signal
      regulated kinase 1 and 2, and preservation of ZO-1 expression. CONCLUSIONS: In
      this study the authors describe a simple and reproducible in vivo animal model of
      surgically induced brain injury. Pretreatment with PP1 results in improved
      outcomes in this model, which suggests a possible role for Src tyrosine kinase
      inhibitors as preoperative therapy for planned neurosurgical procedures.

PMID- 17432723
TI  - Protection of mitochondrial function and improvement in cognitive recovery in
      rats treated with hyperbaric oxygen following lateral fluid-percussion injury.
AB  - OBJECT: Hyperbaric oxygen (HBO2) has been shown to improve outcome after severe
      traumatic brain injury, but its underlying mechanisms are unknown. Following
      lateral fluid-percussion injury (FPI), the authors tested the effects of HBO2
      treatment as well as enhanced normobaric oxygenation on mitochondrial function,
      as measured by both cognitive recovery and cellular adenosine triphosphate (ATP)
      levels. METHODS: Adult male Sprague-Dawley rats were subjected to moderate
      lateral FPI or sham injury and were allocated to one of four treatment groups: 1)
      FPI treated with 4 hours of normobaric 30% O2; 2) FPI treated with 4 hours of
      normobaric 100% O2; 3) FPI treated with 1 hour of HBO2 plus 3 hours of normobaric
      100% O2; and 4) sham-injured treated with normobaric 30% O2. Cognitive outcome
      was assessed using the Morris water maze (MWM) on Days 11 to 15 after injury.
      Animals were then killed 21 days postinjury to assess hippocampal neuronal loss.
      Adenosine triphosphate was extracted from the neocortex and measured using high
      performance liquid chromatography. The results showed that injured animals
      treated with HBO2 or normobaric 100% O2 alone had significantly higher levels of
      cerebral ATP as compared with animals treated using normobaric 30% O2 (p < or =
      0.05). The injured animals treated with HBO2 had significant improvements in
      cognitive recovery, as characterized by a shorter latency in MWM performance (p <
      or = 0.05), and decreased neuronal loss in the CA2/3 and hilar regions as
      compared with those treated with 30% or 100% O2, (p < or = 0.05). CONCLUSIONS:
      Both hyperbaric and normobaric hyperoxia increased cerebral ATP levels after
      lateral FPI. In addition, HBO2 treatment improved cognitive recovery and reduced
      hippocampal neuronal cell loss after brain injury in the rat.

PMID- 17432725
TI  - Ventriculoperitoneal shunt dysfunction in a patient presenting with neurogenic
      pulmonary edema. Case report.
AB  - The authors report on a patient with dysfunction of a ventriculoperitoneal shunt
      who presented with two episodes of neurogenic pulmonary edema within the space of
      a few months. The edema resolved on correction of the shunt dysfunction. Because
      neurogenic pulmonary edema may be a rare consequence of shunt dysfunction, it is
      important to recognize this unusual association and provide appropriate
      diagnostic measures and treatment.

PMID- 17432724
TI  - Motor cortex stimulation: mild transient benefit in a primate model of Parkinson
      disease.
AB  - OBJECT: The authors sought to examine the therapeutic efficacy of motor cortex
      stimulation (MCS) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated
      macaques and to characterize therapeutic differences with varying modes,
      frequencies, and durations of stimulation. METHODS: Motor cortex stimulation was
      delivered at currents below motor threshold and at frequencies between 5 and 150
      Hz through epidural electrodes over the primary motor cortex. The animals were
      studied during and without MCS using video analysis, activity logging, and food
      retrieval tasks. Animals were examined using two different stimulation protocols.
      The first protocol consisted of 1 hour of MCS therapy daily. The second protocol
      exposed the animal to continuous MCS for more than 24 hours with at least 2 weeks
      between MCS treatments. CONCLUSIONS: Daily MCS yielded no consistent change in
      symptoms, but MCS at 2-week intervals resulted in significant increases in
      activity. Effects of biweekly MCS disappeared, however, within 24 hours of the
      onset of continuous MCS. In this study, MCS only temporarily reduced the severity
      of MPTP-induced parkinsonism.

PMID- 17432726
TI  - Comparison of laser surface scanning and fiducial marker-based registration in
      frameless stereotaxy. Technical note.
AB  - The authors compared the accuracy of laser surface scanning patient registration
      using the commercially available Fazer (Medtronic, Inc.) with the conventional
      registration procedure based on fiducial markers (FMs) in computer-assisted
      surgery. Four anatomical head specimens were prepared with 10 titanium
      microscrews placed at defined locations and scanned with a 16-slice spiral
      computed tomography unit. To compare the two registration methods, each method
      was applied five times for each cadaveric specimen; thus data were obtained from
      40 registrations. Five microscrews (selected following a randomization protocol)
      were used for each FM-based registration; the other five FMs were selected for
      coordinate measurements by touching with a point measurement stylus. Coordinates
      of these points were also measured manually on the screen of the navigation
      computer. Coordinates were measured in the same manner after laser surface
      registration. The root mean square error as calculated by the navigation system
      ranged from 1.3 to 3.2 mm (mean 1.8 mm) with the Fazer and from 0.3 to 1.8 mm
      (mean 1.0 mm) with FM-based registration. The overall mean deviations (the
      arithmetic mean of the mean deviations of measurements on the four specimens)
      were 3.0 mm (standard deviation [SD] range 1.4-2.6 mm) with the Fazer and 1.4 mm
      (SD range 0.4-0.9 mm) with the FMs. The Fazer registration scans 300 surface
      points. Statistical tests showed the difference in the accuracy of these methods
      to be highly significant. In accordance with the findings of other groups, the
      authors concluded that the inclusion of a larger number of registration points
      might improve the accuracy of Fazer registration.

PMID- 17432727
TI  - Historical evolution of stereotactic amygdalotomy for the management of severe
      aggression.
AB  - Friedrich Goltz first reported in the 1890s that temporal lobe removal had a
      taming effect in animals. The results of studies by Kluver and Bucy, and later
      Terzian and Ore, demonstrated that an amygdalectomy combined with a temporal
      lobectomy had a significant taming effect in both animals and humans. Based on
      these observations, Narabayashi and colleagues reported the first clinical series
      of patients with temporal lobe epilepsy and/or severe behavioral disturbances in
      which stereotactic amygdalotomy was performed to address aggressive disorders,
      using a frame-based stereotactic device designed by Narabayashi. Use of
      pneumoencephalography, combined with physiological localization by means of
      olfactory stimulation and field potential recordings, enabled these investigators
      to define the lateral part of the amygdala, while simultaneously using wax
      injections to create lesions. Chitanondh used a similar localization technique to
      produce medial amygdala lesions by injecting a mixture of olive oil, wax, and
      iodized oil. In 1966, Heimburger and coworkers reported results from a series of
      25 patients with epilepsy and aggressive behavior who underwent stereotactic
      amygdalotomy. Their technique was slightly different and their target
      localization was solely anatomical, based on pneumoencephalography or contrast
      ventriculography, and they utilized a cryoprobe to make lesions. In 1970,
      Balasubramaniam and Ramamurthi reported the largest clinical series to date on
      this technique; pneumoencephalography or contrast ventriculography was used for
      anatomical localization, and depth electrode recordings were used to obtain
      physiological confirmation of their targets, whereas either diathermy or a
      Bertrand loop was used for making lesions. The development of magnetic resonance
      imaging technology in late 1980 allowed for a more accurate anatomical
      localization of the amygdala, and the improvement of radiofrequency generators
      also made lesioning more precise. Despite these and subsequent technological
      advances, the number of amygdalotomies performed has geometrically decreased
      during the last 20 years.

PMID- 17432728
TI  - History in the making: the AANS celebrates its Diamond Jubilee.

PMID- 17432729
TI  - From manuscript submission to publication: a tour of the Journal of Neurosurgery
      Publishing Group.
AB  - The author offers a "soup-to-nuts" description of day-to-day operations at the
      Journal of Neurosurgery Publishing Group. The route a manuscript follows from
      submission to publication is outlined and placed within the context of a brief
      history of the Journal of Neurosurgery and its related journals.

PMID- 17432730
TI  - Language representation.

PMID- 17432731
TI  - Brain vasospasm after head injury.

PMID- 17432732
TI  - Endoscope or microscope?

PMID- 17432733
TI  - Arteriovenous malformation.

PMID- 17432734
TI  - Balloon-assisted coil embolization.

PMID- 17432735
TI  - Balloon-assisted coil embolization. "Surgical clip application should be
      considered as a first treatment option in large and wide-necked aneurysms".

PMID- 17432736
TI  - Meningiomas of the superior sagittal sinus.

PMID- 17432737
TI  - Substance abuse treatment outcomes for coerced and noncoerced clients.
AB  - This study provides new evidence regarding the relation of coerced care to
      posttreatment substance use and addiction severity while controlling for two
      important factors: readiness to change and addiction severity at admission to
      treatment. The initial study sample consisted of 289 people who agreed to
      participate in a prospective study of substance abuse treatment outcomes in five
      large outpatient programs in Ohio. The findings reported here are based on
      analyses for the 141 (48.8 percent of the original sample) individuals who
      completed a six-month follow-up interview using the short form of the Addiction
      Severity Index. These data indicate that legally coerced participants were more
      likely than noncoerced participants to report abstaining from alcohol and other
      drugs in the 30 days before their follow-up interview. They were also more likely
      to demonstrate reduced addiction severity at follow-up. Readiness to change at
      admission showed no relation to treatment outcomes.

PMID- 17432738
TI  - Experiences and implications of social workers practicing in a pediatric hospital
      environment affected by SARS.
AB  - This phenomenological study's purpose was threefold: to detail the experiences of
      social workers practicing in a hospital environment affected by severe acute
      respiratory syndrome (SARS), to describe essential themes and structures of
      social work practices within this crisis environment, and to explore
      recommendations for better preparedness to meet similar crises in the future. The
      sudden onset of SARS in hospital settings created an immediate necessity to study
      this phenomenon as hospitals and health care professionals struggle to adapt to
      this new epidemic environment. This study is the first using qualitative research
      to investigate the unique perspective of social workers in an epidemic
      environment. The results reflect the social workers' subjective experience of
      their interventions with patients and families and indicate that a number of
      professional tenets, such as advocacy, family-centered approach, knowledge of
      systems, open communication, and ethics effectively supported social work
      practice in a crisis environment.

PMID- 17432739
TI  - Spiritually based resources in adaptation to long-term prostate cancer survival:
      perspectives of elderly wives.
AB  - Spiritually based resources (SBR) generally have a salutary effect on coping with
      cancer diagnosis and treatment. Few studies address this relationship in long
      term cancer survivorship, however. As part of a study on long-term prostate
      cancer survivorship, wives' ways of coping with cancer-related issues were
      explored through longitudinal interviews.This article describes findings from a
      subset of women who reported SBR use (N = 28). Wives completing a quality-of-life
      survey were purposively sampled by age and race and ethnicity and invited to
      participate in semistructured interviews. Interview transcripts were analyzed
      using content analysis and grounded theory. Validity was ensured through
      researchers' consensus, participants' verification, and key informant interviews.
      Although wives' spiritual beliefs were rooted in diverse traditions, common
      themes in SBR use were detected. An embracing spirit was the overarching theme,
      as characterized by acceptance of change, adversity as opportunity for growth,
      and proactive coping. SBR facilitated adaptation in four core areas: marriage
      preservation and couple intimacy, personal growth and continuous learning, health
      related attitudes and behaviors, and community connections. A conceptual model of
      SBR use is proposed, and considerations for research and practice are offered.

PMID- 17432740
TI  - Impact of work requirements on the psychological well-being of TANF recipients.
AB  - Psychological distress was investigated in a group of parents who were current
      and former recipients ofTemporary Assistance for Needy Families (TANF), and a
      group of parents never enrolled in TANF The study focused on two reported
      symptoms of distress: depressive and anxiety symptoms. Analysis incorporated
      cross-sectional data from the Survey of Income and Program Participation, 1996
      panel. Results demonstrate that receiving or having received TANF benefits
      worsened parents' psychological distress. On the other hand, becoming employed
      reduced parents' psychological distress. Furthermore, participants' physical
      health state was significantly and negatively related to their psychological
      distress. Reliance on general assistance (before or after leaving TANF) was
      associated with psychological distress, although other social support variables
      (such as availability of child care, Medicaid, food stamps, and so forth) had no
      significant effect on psychological distress among current or former TANF
      recipients. Implications of the findings for policy and intervention are
      discussed.

PMID- 17432741
TI  - Parental influence, gay youths, and safer sex.
AB  - To begin to understand the role that family relationships and interactions play
      in young gay men's decisions to avoid unsafe sexual practices, parents and sons
      (ages 16 to 25) in 30 families were qualitatively interviewed about issues and
      concerns related to HIV risk. Most of the youths reported feeling obliged to
      their parents to stay healthy, and these feelings of obligation were important
      factors in their decisions to avoid unsafe sex. Youths who reported no parental
      influence came from families in which parents had historically been preoccupied
      with personal or marital problems or in which there was a history of parental
      rejection. On the basis of these exploratory findings, AIDS prevention
      specialists are advised to recruit parents, assess family relationships, and
      facilitate parent-child communication in their efforts to encourage gay youths to
      consistently engage in safer sex practices.

PMID- 17432742
TI  - Predictors of health service barriers for older Chinese immigrants in Canada.
AB  - Elderly people from ethnic minority groups often experience different barriers in
      accessing health services. Earlier studies on access usually focused on types and
      frequency but failed to address the predictors of service barriers. This study
      examined access barriers to health services faced by older Chinese immigrants in
      Canada. Factor analysis results indicated that service barriers were related to
      administrative problems in delivery, cultural incompatibility, personal
      attitudes, and circumstantial challenges. Stepwise multiple regression showed
      that predictors of barriers include female gender, being single, being an
      immigrant from Hong Kong, shorter length of residency in Canada, less adequate
      financial status, not having someone to trust and confide in, stronger
      identification with Chinese health beliefs, and not self-identified as Canadian.
      Social work interventions should strengthen support and resources for the
      vulnerable groups identified in the findings. Service providers should adjust
      service delivery to better serve elderly immigrants who still maintain strong
      Chinese cultural values and beliefs.

PMID- 17432743
TI  - Reducing depression among adolescents dealing with grief and loss: a program
      evaluation report.

PMID- 17432744
TI  - Strengths-oriented referrals for teens (SORT): giving balanced feedback to teens
      and families.

PMID- 17432745
TI  - Intervention approaches to driving and dementia.

PMID- 17432746
TI  - Article's methodology is questionable.

PMID- 17432747
TI  - Passage to India.

PMID- 17432748
TI  - Field medicine.

PMID- 17432749
TI  - Transplant travel guide.

PMID- 17432750
TI  - Hidden hurt.

PMID- 17432751
TI  - Reform group puts forward bill.

PMID- 17432752
TI  - Open to interpretation.

PMID- 17432753
TI  - Global health hot zone.

PMID- 17432754
TI  - Lessons from Rwanda.

PMID- 17432755
TI  - Songs for Wakinesh.

PMID- 17432756
TI  - When the market fails, the poor pay.

PMID- 17432757
TI  - Hearing hoofbeats, thinking zebras: five diseases common among refugees that
      Minnesota physicians need to know about.
AB  - Minnesota accepts more refugees per capita than any other state. For that reason,
      primary care physicians throughout the state are likely to encounter refugees in
      their practices. This article describes 5 infectious diseases that are common
      among refugees and what physicians need to know about them in order to
      effectively screen and treat patients who are newcomers to this country. The
      diseases discussed are strongyloides, schistosomiasis, malaria, hepatitis B, and
      tuberculosis.

PMID- 17432758
TI  - Global climate change and human health.
AB  - Global climate change is a vexing economic, environmental, and public health
      problem. Climatologists have documented a rise in global average temperature that
      is unprecedented since the Industrial Revolution. This temperature change
      correlates with increasing concentrations of atmospheric carbon dioxide (CO2) and
      other greenhouse gases, which largely are of human origin. Global climate change
      is likely to profoundly affect global health. This article summarizes the science
      of climatology and global climate change caused by human actions and reviews
      potential health effects.

PMID- 17432759
TI  - The "healthy migrant" effect.
AB  - In many ways, first-generation immigrants to the United States are healthier than
      people of similar ethnic backgrounds who were born in this country. However,
      overtime, the newcomers' health advantages diminish dramatically. This article
      discusses factors that contribute to the deterioration of immigrants' health:
      poverty, living in substandard housing, not having access to medical care,
      adoption of an American diet, smoking, and substance abuse.

PMID- 17432760
TI  - The radiologist is no longer the outsider.

PMID- 17432761
TI  - The provision of emergency radiology services and potential radiologist workforce
      crisis: is there a role for the emergency-dedicated radiologist?
AB  - One of the greatest challenges facing the specialty of radiology over the next
      several years will involve the provision of emergency radiology services. The
      demand for medical imaging--especially computed tomography and magnetic resonance
      imaging--continues to explode in the emergency setting and threatens to overwhelm
      the resources of many radiology practices. How our specialty decides ultimately
      to respond is critical, as it will have far-reaching implications, which will
      define the role and perceived value of the radiologist in all settings for years
      to come.

PMID- 17432762
TI  - On-call radiology: community standards and current trends.
AB  - The issues regarding on-call radiology are complex and contentious. Both academic
      and private practice radiology centers have encountered increasing workloads in
      recent years. Some academic centers are utilizing night float systems or other
      models of call to address the increasing complexity and volume of after-hours
      cases. Many private practice groups are outsourcing after-hours work to
      commercial nighthawk radiology services. Emergency medicine department and ACR
      guidelines place additional expectations on the on-call radiologist.

PMID- 17432763
TI  - Controversies in "clearing" trauma to the cervical spine.
AB  - Clearance of the traumatic cervical spine is a subject affecting most healthcare
      professionals dealing with trauma patients. There is a host of often
      contradictory literature making it hard for an interested reader to come to their
      own informed opinion based on the current evidence. This review aims to outline
      the relevant literature for the clearance of the traumatic cervical spine with
      the particular aim of highlighting the contradictions, controversies and
      unanswered questions still besetting this important subject. A brief, subjective
      opinion for a combined clinical and imaging protocol for clearance of the
      traumatic cervical spine is given.

PMID- 17432764
TI  - Screening for blunt cerebrovascular injuries: the essential role of computed
      tomography angiography.
AB  - The implementation of aggressive diagnostics refuted the thesis that blunt
      cerebrovascular injuries (BCVI) are rare events. Given the estimates from recent
      studies, the prevalence may be as high as 1 per 100 among blunt multiple trauma
      patients. The morbidity and mortality of unrecognized and untreated BCVI is
      exceptionally high and warrants distinct efforts to detect these injuries during
      the primary trauma survey. The primary goal is to detect BCVI before neurological
      symptoms occur, and to introduce anticoagulation or antiplatelet therapy as
      appropriate. Index injuries such as cervical spine fractures increase the prior
      probability of disease, but are not helpful in ruling BCVI out. Computed
      tomography angiography (CTA) may represent the screening tool of choice, although
      there is still limited evidence about its accuracy. Pooled data from six studies
      (1368 patients) published between 2002 and 2006 suggest a sensitivity of 79% and
      a specificity of 97% in the trauma setting. In the two largest investigations, no
      false negative results were observed. Further research is needed to determine the
      efficacy of CTA for disclosing BCVI, and to evaluate the potential benefits to
      patients.

PMID- 17432765
TI  - Evaluation of acute chest pain in the emergency department: utility of
      multidetector computed tomography.
AB  - Distinguishing insignificant from life-threatening causes of acute chest pain in
      patients who present to the emergency department remains a major challenge.
      Initial evaluation with history, electrocardiography, and biochemical markers is
      often unrevealing leading to additional workup. Radionuclide perfusion and
      echocardiography may be diagnostic but provide only indirect assessment of
      coronary status. The development of multidetector computed tomography (MDCT) and
      its increasingly frequent placement near the emergency suite has facilitated its
      use for the evaluation of serious noncardiac diagnoses such as pulmonary embolism
      and aortic dissection. Recent innovations in MDCT technology have facilitated the
      depiction of coronary arteries. These advances have led to the possibility of
      using CT to evaluate cardiac etiologies of chest pain, using either a
      comprehensive or triple rule out protocol to assess both cardiac and noncardiac
      causes or a dedicated coronary protocol. This article will review both options
      and describes our preliminary experience with the first of these protocols. The
      article also reviews the potential value of an acute chest pain CT protocol and
      the considerable challenges that remain prior to its implementation for routine
      clinical use.

PMID- 17432766
TI  - Blunt abdominal trauma: current imaging techniques and CT findings in patients
      with solid organ, bowel, and mesenteric injury.
AB  - Imaging plays a critical role in the evaluation of patients with blunt abdominal
      trauma. In most institutions, computed tomography (CT) is the modality of choice
      when evaluating such patients. The purpose of this review is to highlight current
      techniques in trauma imaging and to review CT findings associated with solid
      organ, bowel, mesenteric, and diaphragmatic injury. In particular, emphasis is
      placed on the use of multidetector CT technology (MDCT), especially 64-row
      detector CT. The role of various techniques, including the use of oral and
      intravenous contrast, as well as the potential benefit of delayed imaging, is
      discussed.

PMID- 17432767
TI  - Contrast-enhanced ultrasound for blunt abdominal trauma.
AB  - Sonography is widely used in the initial diagnostic assessment of blunt abdominal
      trauma in adults and children. It has been formally incorporated worldwide into
      the routine armamentarium available for emergency diagnosis and treatment as a
      means of rapid detection of free abdominal fluid, normally referred to as FAST
      (Focused Assessment with Sonography in Trauma). However, there is some
      controversy regarding its value because free abdominal fluid may be lacking in
      patients with abdominal organ injuries from blunt trauma. More recently, a new
      ultrasound technique has been developed using contrast agents. Contrast-enhanced
      ultrasound performs better than the non-contrast-enhanced technique for the
      detection of abdominal solid organ injuries and can play an important role in the
      prompt evaluation of patients with blunt trauma. Furthermore, contrast-enhanced
      ultrasound can be used in the follow-up of patients who have solid organ lesions
      and are managed with nonoperative treatment, avoiding radiation and iodinated
      contrast medium exposure.

PMID- 17432768
TI  - MRI for traumatic knee injury: a review.
AB  - Magnetic resonance imaging (MRI) is a well-established technique for detecting
      internal derangements of the knee joint with high diagnostic accuracy. It is an
      effective tool to select patients for targeted therapeutic arthroscopy. In this
      article, indications for knee MRI and most commonly used MRI techniques are
      outlined, followed by an overview of the most frequently encountered traumatic
      knee derangements in daily practice and their appearance and grading system on
      MRI. Lesions discussed include fractures, osteochondral lesions, bone bruise,
      cruciate and collateral ligament lesions, and meniscal tears. Finally, common
      pitfalls and recent developments in knee MRI are addressed.

PMID- 17432769
TI  - Emergency pediatric imaging: current status and update.
AB  - Imaging has undergone a major revolution. Many procedures performed 20 years ago
      are no longer performed and new ones have expanded our ability to diagnose
      previously hidden conditions and also our knowledge of these conditions. This
      communication deals both with modern imaging and how it is affecting our
      evaluation of certain diseases but yet underscores that plain film findings still
      are important and should not be cast by the wayside in favor of more modern cross
      sectional imaging.

PMID- 17432770
TI  - The effects of antihypertensive medication on dental treatment.
AB  - Hypertension is a medical problem that impacts on health worldwide. A number of
      different medications are used to treat hypertension. These drugs can affect the
      mouth and perioral structures and impact upon dental management. It is therefore
      important that dentists are aware of the side-effects and relevant drug
      interactions that occur in patients on antihypertensive medication. CLINICAL
      RELEVANCE: Dentists will encounter patients receiving antihypertensive therapy
      and should be aware of how these drugs impact upon dental treatment.

PMID- 17432771
TI  - Modern restorative management of patients with congenitally missing teeth: 4. The
      role of implants.
AB  - In this fourth and final paper on the management of patients with congenitally
      missing teeth, the use of dental implants is considered. This group of patients
      often provides unique challenges when implant reconstruction is considered. Often
      a multidisciplinary approach is required involving orthodontists, oral surgeons
      and restorative dentists. The use of dental implant systems is a rapidly
      developing area of dentistry and its implications on hypodontia are discussed.
      This paper identifies the problems associated with a congenital absence of teeth
      and addresses their management in relation to the use of implants. CLINICAL
      RELEVANCE: The use of dental implants in hypodontia patients should always be
      considered as a treatment option. These groups of patients, however, require
      careful planning, often of a multidisciplinary nature, so that the timing of the
      various treatment modalities is seamless.

PMID- 17432772
TI  - Patient-centred measures in dental practice: 3. Patient satisfaction.
AB  - This, the final paper in this three-part series, looks at how patients evaluate
      the dental care they receive and how this translates into either satisfaction,
      dissatisfaction or something in between. It explains how it might be possible to
      manage patient expectations so that patients are more likely to be satisfied with
      all aspects of the care provided and describes a framework for dentists and staff
      to use when trying to enhance patient experience in everyday dental practice.
      CLINICAL RELEVANCE: By better understanding the concept of 'patient satisfaction'
      dentists can develop strategies that take into account the way patients evaluate
      the quality of their own dental care.

PMID- 17432773
TI  - Cosmetic rehabilitation following successful treatment of aggressive
      periodontitis.
AB  - With advances in periodontal therapy, many sufferers from aggressive
      periodontitis are retaining their teeth after successful treatment. This presents
      the practitioner with aesthetic and restorative challenges in these relatively
      young patients. Lifelong motivation is essential to the supportive therapy for
      these patients, and the maintenance of good aesthetics, combined with
      biologically acceptable corrective therapy, may help maintain a high level of
      motivation. Any treatment provided must naturally be conducive to maintaining
      long-term dental and periodontal health. This paper aims to demonstrate options
      for dealing with the aesthetic challenges posed by a number of patients who have
      undergone initial cause-related therapy for aggressive periodontitis. CLINICAL
      RELEVANCE: Loss of gingival tissue, tooth positional changes and tooth loss
      present practitioners with challenges in relation to patient satisfaction with
      aesthetics following advanced periodontal breakdown. A range of techniques will
      be required, tailored to the consequences of periodontal attachment loss, in
      order to satisfy patient demands.

PMID- 17432774
TI  - Conservative aesthetic techniques for discoloured teeth: 1. The use of bleaching.
AB  - There is an increasing move towards more minimally invasive techniques in
      restorative dentistry. This series of two articles discusses conservative
      techniques for the treatment of discoloured teeth. A step-wise approach to
      treatment is promoted to encourage the most conservative solution to achieve
      satisfactory aesthetics. The first of these two articles will describe the use of
      bleaching, whilst part two will go on to describe microabrasion and the use of
      direct composite resin. CLINICAL RELEVANCE: Discoloured teeth are a common dental
      problem. Bleaching provides a simple conservative solution in many cases.

PMID- 17432775
TI  - Management of the anxious patient: what treatments are available?
AB  - Fear of the dentist is a common phenomenon. There are many ways of dealing with
      anxious patients and this review aims to present the most common methods
      available to general dental practitioners. CLINICAL RELEVANCE: An ability to deal
      with anxious patients successfully is undoubtedly a practice builder. Anxious
      patients can be stressful to manage but they often become the most vocal
      advocates of dentists that they trust.

PMID- 17432776
TI  - Dental management of a child patient with Noonan's syndrome.
AB  - This case report describes a 9-year-old Caucasian girl who required comprehensive
      dental treatment under general anaesthesia but gave a history of Noonan's
      syndrome. The patient was extremely needle phobic. Because of the association
      between Noonan's syndrome and underlying coagulopathies, for which no previous
      investigations were evident, dental treatment had to be postponed pending further
      investigation. The patient was referred to a haematologist and underwent
      coagulation screening, which revealed the presence of von Willebrand's disease.
      The patient was prescribed Desmopressin to raise plasma levels of factor VIII: C
      and von Willebrand's factor (VWF) in order that dental treatment, including
      extractions, could be carried out under an in-patient general anaesthetic.
      CLINICAL RELEVANCE: Congenital heart defects and bleeding diatheses are regarded
      as a common association of Noonan's syndrome. Witt et al estimated that around
      one-third of the patients have an associated bleeding disorder, although a later
      report suggested that as many as 74% of the coagulation profiles could be
      abnormal. Most of the bleeding problems are reported to be mild, and resolve with
      age in some patients, but, clearly, they may cause problems during dental
      treatment, necessitating haematological investigations and a multidisciplinary
      approach.

PMID- 17432777
TI  - Ectopic geographic tongue--a case report.
AB  - This report describes a case of 'ectopic' geographic tongue where lesions,
      clinically and histologically similar to those normally confined to the tongue,
      presented on the floor of the mouth and cheek mucosa. The patient, a type II
      diabetic, had a history of thrombocytopaenia and, more recently, autoimmune
      haemolytic anaemia. CLINICAL RELEVANCE: Geographic tongue is a common oral
      medicine condition and the purpose of this paper is to highlight the fact that it
      can present ectopically on the oral mucosa.

PMID- 17432778
TI  - Physical signs for the general dental practitioner. Acanthosis nigricans.

PMID- 17432779
TI  - Aspects of human disease. 9. Chronic obstructive pulmonary disease (COPD).

PMID- 17432780
TI  - The patient's role in understanding treatment prognosis.

PMID- 17432781
TI  - An examination of immediately loaded dental implant stability in the diabetic
      patient using resonance frequency analysis (RFA).
AB  - OBJECTIVES: To evaluate the stability of 18 immediately loaded Branemark System
      dental implants in an insulin-controlled, diabetic, 71-year-old patient over the
      first 30 months after surgery, and to correlate this data with implant stability
      in healthy patients. METHOD AND MATERIALS: Stability measurements were taken
      using resonance frequency analysis on all implants at surgery placement and at 5
      postsurgical examinations (1, 2, 3, 6, and 30 months). RESULTS: All 18 implants
      remained in function after 2.5 years of follow-up. The mean stability of the
      implants decreased 12.7% during the first 30 days, a value twice as much as seen
      in the general population. After the first 30 days, the stability of the implants
      increased slightly over the next 60 days. After 30 months of follow-up, the mean
      implant stability continued to increase, however, not to a value equal to that of
      the initial measurement taken at the time of implant placement. CONCLUSION:
      Despite the metabolic differences seen in diabetic patients, an immediate loading
      protocol can be successful and result in osseointegration.

PMID- 17432782
TI  - Retrospective study of 200 immediately loaded implants retaining 50 mandibular
      overdentures.
AB  - OBJECTIVE: To perform a retrospective study on immediately loaded implants
      supporting mandibular overdentures. METHOD AND MATERIALS: From the period between
      July 1996 and October 2004, 50 patients were selected in whom 200 implants had
      been inserted (4 implants per patient) in the interforaminal area, rigidly
      connected with a U-shaped bar, and then loaded with a mandibular overdenture.
      Implant diameter and length ranged from 3.4 to 5.5 mm and from 10.0 to 18.0 mm,
      respectively. Sixty implants were placed after extraction, and bone quality was
      D1 in 22 cases and D2 in 178 cases. Because no implants were lost (ie, survival
      rate, 100%) and no statistical differences were detected among the studied
      variables, no or reduced crestal bone resorption was considered as an indicator
      of success rate to evaluate the effect of several host-, surgery-, and implant
      related factors. A general linear model was then performed to detect those
      variables statistically associated with crestal bone resorption. RESULTS: No
      implants were lost (ie, survival rate, 100%) after a mean postloading follow-up
      of 43 months, and thus no differences were detected among the studied variables.
      On the contrary, the general linear model showed that longer (ie, length > 13.0
      mm) and wider (ie, diameter > 3.75 mm) implants and implant type (Frialoc and
      XiVE TG) are correlated with a lower crestal bone resorption and thus a better
      outcome. CONCLUSION: Immediate loading of implants retaining a mandibular
      overdenture is a reproducible, predictable, and reliable method to deliver
      efficient return of function for totally edentulous patients.

PMID- 17432783
TI  - Recurring acinic cell carcinoma of the buccal mucosa: a case report.
AB  - A case of acinic cell adenocarcinoma of the left facial area of 10-years'
      duration in a 29-year-old man is presented. The patient reported surgical
      resection of a nodular lesion in the left buccal mucosa 8 years earlier in
      another hospital. Since then, the lesion recurred 3 times within 2 years. The
      first lesion and 2 recurrent ones were surgically removed. With the third
      recurrent lesion, the patient did not return promptly for treatment and was
      directed to our clinic after 6 years. The clinical, tomographic,
      immunohistochemical, and therapeutic aspects are analyzed.

PMID- 17432784
TI  - Prevention of alveolar osteitis with azithromycin in women according to use of
      tobacco and oral contraceptives.
AB  - OBJECTIVE: To evaluate the efficacy and tolerance of azithromycin in the
      prevention of post-extraction alveolar osteitis (dry socket) in women according
      to their use of tobacco and oral contraceptives. METHOD AND MATERIALS: A clinical
      trial was conducted in 400 women who underwent tooth extraction, stratified into
      4 risk groups according to their use of tobacco (yes/no) and oral contraceptives
      (yes/no). Each stratum (n = 100) was randomly divided into 2 groups: a study
      group that received azithromycin 500 mg once daily for 3 days after extraction
      and a control group that received physiologic saline 3 times daily from 24 hours
      after extraction for 7 days. RESULTS: Azithromycin was significantly superior to
      conventional postextraction treatment with physiologic saline. There were no
      significant interactions with the use of either tobacco or oral contraceptives,
      and these variables had no confounding effects. CONCLUSION: Azithromycin is a
      safe and efficacious treatment for the prevention of dry socket in women.

PMID- 17432785
TI  - Comparison of electrolyte concentrations in whole saliva of individuals with and
      without cerebral palsy.
AB  - OBJECTIVE: To analyze sodium, potassium, calcium, phosphorus, and magnesium
      concentrations in whole saliva of adolescents with cerebral palsy (CP) and
      compare them with those of normal individuals. METHOD AND MATERIALS: Thirty-six
      adolescents with CP aged 12.0 +/- 1.8 years were compared with 36 healthy age
      matched individuals. Saliva was collected under slight suction. Electrolyte
      concentrations were determined by inductively coupled argon plasma with atomic
      emission spectrometry. RESULTS: Significant differences were observed with
      matched and unmatched flow rates. Sodium concentrations were significantly
      decreased, whereas potassium levels were significantly increased in the CP group.
      No statistically significant differences were observed regarding phosphorus,
      magnesium, and calcium concentrations between adolescents with CP and controls.
      CONCLUSION: Our results suggest that there is an alteration in the sodium and
      potassium concentration in whole saliva of individuals with CP.

PMID- 17432786
TI  - Laser treatment of an oral papilloma in the pediatric dental office: a case
      report.
AB  - Squamous cell papilloma is a benign proliferation of the stratified squamous
      epithelium. It is typically an exophytic lesion smaller than 1 cm. Its appearance
      varies from cauliflower-like to fingerlike, while the base may be pedunculated or
      sessile. This article describes the case of an 11-year-old girl who presented
      with an asymptomatic whitish lesion of papillomatous appearance in the oral
      mucosa distal to the maxillary left permanent first molar. The lesion was removed
      using an Er,Cr:YSGG laser. For anesthesia, 10 mg of 2% lidocaine with epinephrine
      1:100,000 was infiltrated around the lesion. No pain medication was required
      after surgery, and wound healing was excellent and rapidly achieved. The oral
      pathology report confirmed the presurgical clinical diagnosis. Laser dentistry is
      a modern technology that can be used by dental clinicians to treat these kinds of
      oral lesions and should be considered as an alternative to conventional surgery.

PMID- 17432787
TI  - Role of remineralizing fluid in in vitro enamel caries formation and progression.
AB  - OBJECTIVE: To evaluate a remineralizing fluid for its influence on in vitro
      caries formation and progression. METHOD AND MATERIALS: Caries-free teeth (n =
      12) were sectioned into 3 segments. Each segment was assigned to a treatment
      group: (1) remineralizing fluid for 2 minutes; (2) 1.23% acidulated phosphate
      fluoride (APF) gel for 1 minute; (3) no-treatment control. Following treatment,
      the tooth segments were rinsed in distilled/deionized water and exposed to
      synthetic saliva for 24 hours. In vitro caries were formed and longitudinal
      sections obtained. The tooth segments were treated again and rinsed as above,
      before undergoing in vitro caries progression. Longitudinal sections were
      evaluated for lesion depth (ANOVA, Duncan multiple range analysis). RESULTS:
      Following lesion formation, mean lesion depths were 173 +/- 19 microm for no
      treatment control; 97 +/- 11 microm for APF gel; and 52 +/- 12 microm for
      remineralizing fluid. After lesion progression, mean lesion depths were 236 +/-
      23 microm for no-treatment control; 184 +/- 26 microm for APF gel; and 112 +/- 17
      microm for remineralizing fluid. Mean lesion depths for the remineralizing fluid
      and APF gel groups for the lesion formation and progression periods were
      significantly less than those for the control group (P < .05). After lesion
      formation and progression, the APF group had significantly greater mean lesion
      depths than did the remineralizing fluid group (P < .05). CONCLUSIONS: A
      remineralizing fluid containing calcium, phosphate, and fluoride in a carbopol
      base enhanced resistance against in vitro caries formation and progression when
      compared with APF treatment.

PMID- 17432789
TI  - Risk stratification and dental management of patients with adrenal dysfunction.
AB  - Intrinsic and extrinsic physiological stressors (physical, metabolic, or
      psychological) are constantly challenging the body's homeostatic mechanisms.
      Regardless of their nature, the body will initiate a series of autonomic
      responses in an effort to maintain homeostasis. For example, to cope with a
      perceived threat, cardiac output and respiration are increased, the availability
      of glucose is increased, and blood flow to the heart, brain, and muscles is
      increased. Conversely, once the threat subsides, conter-regulatory mechanisms act
      to down-regulate these responses. The adaptive stress response is essential for a
      patient's well-being. An altered adaptive stress response may lead to illness,
      and, at times, even to death. Oral healthcare providers must develop preventive
      and therapeutic strategies compatible with the functional capacity of a patient's
      adaptive stress response.

PMID- 17432788
TI  - Foods and dietary factors that prevent dental caries.

PMID- 17432790
TI  - Effect of bleaching agents on calcium loss from the enamel surface.
AB  - OBJECTIVES: To compare the Ca2+ loss of enamel treated with 38% hydrogen peroxide
      (HP), 35% HP with light, and 10% carbamide peroxide (CP). METHOD AND MATERIALS:
      Ten extracted premolars were sectioned buccolingually and longitudinally so that
      4 specimens were obtained from each tooth. The specimens were randomly assigned
      to 1 of 4 groups to receive the following bleaching agents: 38% HP, 35% HP with
      light, 10% CP, and no agent (control). The specimens were treated with an
      artificial caries solution (pH 4) for 16 days; the solution was replaced on days
      4, 8, 12, and 16. Calcium concentration was determined by an atomic absorption
      spectrophotometer. Repeated measures ANOVA was performed on concentrations on
      days 4, 8, 12, and 16. RESULTS: At the end of day 16, calcium ions released per
      square millimeter were calculated cumulatively as follows: 38% HP group: 27.52 +/
      5.22 microg/mL; 35% HP with light group: 25.15 +/- 4.99 microg/mL; 10% CP group:
      19.53 +/- 4.03 microg/mL; control group: 18.35 +/- 4.00 microg/mL. The
      differences between the control group and the 35% HP with light group and between
      the control group and 38% HP group were statistically significant. Although
      demineralization differences were observed between the control group and the 10%
      CP group, this difference was not significant. CONCLUSIONS: It can be concluded
      that 35% HP with light and 38% HP may cause significantly more loss of Ca2+ from
      the enamel surfaces than 10% CP. Also, 10% CP does not vary significantly from
      the control.

PMID- 17432791
TI  - Mesenchymal chondrosarcoma of the left coronoid process: report of a unique case
      with clinical, histopathologic, and immunohistochemical findings, and a review of
      the literature.
AB  - Mesenchymal chondrosarcoma (MCS) is a rare malignant neoplasm of bone or soft
      tissue origin, locally aggressive, rare in the oral cavity, of which fewer than
      100 cases have been reported in the English literature. This is the first case
      described of this type of tumor affecting the coronoid process. The report
      describes a unique case of MCS in a 64-year-old woman who presented with swelling
      and pain at the left preauricular area just anterior to the left tragus. An
      orthopantomograph showed a large mass in the temporomandibular joint involving
      the left coronoid process and extending to the left ramus of the mandible. Biopsy
      and histopathologic examination revealed a biphasic pattern, composed of an
      undifferentiated small round-cell component surrounding a myxoid of malignant
      cartilage; a focally pericytic vascular pattern resembling hemangiopericytoma was
      observed. Immunohistochemical studies were positive for CD99, S-100, and CD45 and
      negative for desmin, actin, chromogranin, epithelial membrane antigen (EMA), and
      cytokeratin. The tumor was treated by extensive hemimandibulectomy followed by
      reconstruction of the area. There was no evidence of disease at the 8-year follow
      up. Previously reported cases are reviewed as well.

PMID- 17432792
TI  - [Health food preparations are not harmless. Ask about over-the-counter drugs and
      dietary supplements during every medication anamnesis].

PMID- 17432793
TI  - [Closure of secundum atrial septal defects in children and adolescents. Both
      catheterization and open surgery are needed in the therapeutic arsenal].

PMID- 17432794
TI  - [Can child homicides be prevented? New law concerning child fatality review
      proposed to be instituted in July].

PMID- 17432795
TI  - [Traumatic memories can be effectively treated with EMDR].

PMID- 17432796
TI  - [Prostasomes and exosomes--cell messengers with therapeutic potentials].

PMID- 17432797
TI  - [Health food preparations have caused several cases of severe lead poisoning. At
      least four cases in Sweden after intake of an ayurvedic preparation].

PMID- 17432798
TI  - [Young physicians are needed as leaders and executives in modern health care!].

PMID- 17432799
TI  - [What do we require of leaders in health care?].

PMID- 17432800
TI  - [Don't underestimate the value of transgenic animal models of Alzheimer disease].

PMID- 17432801
TI  - [Evidence and eminence--what applies to modern health care?].

PMID- 17432802
TI  - [Watch the time!].

PMID- 17432803
TI  - [Interesting Canadian study on waiting times].

PMID- 17432804
TI  - ["Sick music"--experienced illness that set traces in music].

PMID- 17432805
TI  - [Women pioneers laid the way for the increasing number of women physicians of
      today].

PMID- 17432806
TI  - Assessment in medical education.

PMID- 17432807
TI  - Chronic asthma in adults.

PMID- 17432808
TI  - Sinus headache: a clinical dilemma.

PMID- 17432809
TI  - The use of intrapartum electronic fetal heart rate monitoring: a national survey.
AB  - This study describes the use of intrapartum electronic fetal monitoring in
      Ireland. Electronic fetal monitoring (EFM) has become routine in the assessment
      of fetal wellbeing during labour. Current evidence indicates that the routine use
      of EFM leads to an increased caesarean section and operative vaginal delivery
      rate and a reduction in the rate of neonatal seizures. Practices and service
      provision related to the use and interpretation of and educational provision for
      electronic fetal monitoring have not been investigated in Ireland. A national
      survey of all (n = 22) maternity units in Ireland was undertaken using a self
      reported questionnaire amended, with permission, from that used in the 8th CESDI
      report. The questionnaire sought information on unit birth rate in 2002, number
      of cardiotocograph (CTG) monitors available in delivery units, use of the
      admission CTG, use of continuous EFM for women with various risk factors for
      pregnancy and/or labour, availability of fetal blood sampling facilities, use of
      umbilical cord blood sampling and availability of guidelines on the use of EFM.
      All units responded to the survey giving a national picture of the use of EFM
      during labour. All units had cardiotocograph (CTG) monitors available in the
      delivery area (median 6, range 3-14). An admission CTG was performed on all women
      by 96% (n=21) of units. Thirty six per cent of units (n=8) used continuous EFM
      routinely during labour in women who did not have risk factors for labour. Fetal
      blood sampling (FBS) was used in 36% (n=8) of units in cases of suspicious CTG
      tracings. Umbilical cord blood gases were sampled routinely following emergency
      caesarean section in 46% (n= 10) of units while 64% (n= 14) did so if the baby's
      condition was poor at birth. A departmental guideline on the use of EFM was
      available in 73% (n= 16) units. The findings of this survey indicate wide
      variations in the use of intrapartum EFM in Ireland. The use of continuous EFM
      for specific high-risk indications was variable and EFM was used by a third of
      units for women who did not have risk factors for labour. The admission CTG was
      used by 21 of the 22 units despite evidence of no benefit. The absence of FBS in
      the majority of units surveyed and the low rate of umbilical cord blood sampling
      is of concern.

PMID- 17432810
TI  - Access of asylum seeker children to acute paediatric services.
AB  - To investigate the interface between primary care and paediatric services in the
      referral of asylum seekers. Over a 3 month period a questionnaire was
      administered, and clinical data gathered on every child attending the A&E
      department of UCHG whose parents were seeking asylum in this country. Control
      data was obtained for the next Irish child seen on-call. At the time of
      presentation to the paediatric service, an Irish child was 4 times more likely
      (32%) to have initially been seen and referred by a GP than an asylum seeker
      child (8%); 80% of asylum seeker families had registered with a GP, compared to
      96% of controls. 24% of asylum seeker families had called and used an emergency
      response ambulance to get to hospital, compared to just 4% of Irish children. The
      rate of subsequent admission to the paediatric ward from A&E was nearly that in
      asylum seeker children (24%) compared to Irish controls (40%), get to hospital,
      compared to just 4% of Irish children. Asylum seeker children are less likely to
      have seen a GP prior to A&E presentation, more likely to go to hospital by
      ambulance and less likely to be subsequently admitted, suggesting an over
      dependence on paediatric hospital services in this population.

PMID- 17432811
TI  - Asthma knowledge amongst paediatric trainees and parents.
AB  - To achieve asthma control adequate knowledge of the disease is required.
      Knowledge levels of thirty five specialist registrars and one hundred and sixty
      parents of children attending an asthmatic clinic, prior to entry into a
      formalised asthma educational program, were assessed utilising a twenty stem
      questionnaire with eighty five statements. Three out of thirty five specialist
      registrars had adequate knowledge levels whilst the other thirty two had
      potentially adequate knowledge levels. Sixty two out of one hundred and sixty
      parents had potentially adequate knowledge levels and the other ninety eight had
      inadequate knowledge levels. Parental knowledge can be improved by formal
      educational programs. Deficiencies in doctors' knowledge should be addressed
      through a similar program rather than rely on experiential learning.

PMID- 17432812
TI  - Epidemiology of hepetitis C infection, ERHA/HSE Eastern region.
AB  - Hepatitis C became statutorily notifiable in Ireland on 1 January 2004. Prior to
      2004, only hepatitis A and hepatitis B were notifiable as distinct types of
      hepatitis. A third category notifiable under the Infectious Diseases Regulations
      1981 was "viral hepatitis unspecified". The majority of cases notified under this
      heading were thought to be due to infection with hepatitis C Virus (HCV). Between
      January 1 2004 and December 31 2005, the Department of Public Health HSE Eastern
      Region, received notification of 2,014 cases of HCV infection (2004, 941 cases,
      2005 1,073 cases). This report outlines basic demographic details on cases
      notified and comments on missing data. Peak age band at notification for males
      and females is in the 25-29 year old age group where 538 (26.7%) were notified.
      Thirty cases notified (1.5%) were under 15 years of age. Drug misuse has been
      confirmed as a risk factor for 1247 (61.9%) of cases notified, and may be a risk
      factor in a large percentage of the reminder where risk factor data are unknown.
      Problems with completeness of notification have been identified. Enhanced
      surveillance of all hepatitis C infections is a prerequisite for future service
      planning.

PMID- 17432813
TI  - Lung cancer and urban air-pollution in Dublin: a temporal association?
AB  - In 1990, the sale, marketing and distribution of bituminous coal, primarily used
      for domestic heating, were banned across Dublin. This study exploits the
      potential of a 'natural experiment' to assess a temporal association between
      adjusted annual lung cancer death rates and the changing annual mean urban air
      pollution concentrations in Dublin from 1981 to 2000. Annual mean 'black smoke'
      (BS) concentration was used as an indicator variable for the urban air-pollution
      mixture. Log-linear Poisson regression model (with an offset) was used to
      estimate adjusted rate ratios of lung cancer death rates between two periods
      (1981-1990 and 1991-2000) relative to the year 1990. A significant (p<0.0001) two
      third decline in BS concentration (28.2 microg/m(3)) was seen between the two
      periods [pre-ban (46.4 microg/m(3)) vs. post-ban (18.2 microg/m(3))]. Relative to
      1990 (rate ratio= 1 ), a slightly greater decline (2%) in death rates was
      achieved in the pre-ban period (1981-1990) when mean annual BS concentrations
      were very high, but a lower decline (1%) was seen in the post-ban period (1991
      2000) corresponding to very low mean annual BS concentrations. In other words, a
      further fall in adjusted rates in lung cancer was achievable both in the pre-ban
      and the post-ban periods when simultaneously controlling for BS and smoking. A
      temporal association thus observed between lung cancer death rates and the
      changing BS concentrations suggests that control of particulate air-pollution
      could further reduce lung cancer rates, irrespective of smoking patterns.

PMID- 17432814
TI  - Expanding the clinical spectrum of central pontine myelinolysis.
AB  - Central Pontine Myelinolysis (CPM) is a clinical entity first described by Adams
      et all in 1958 in the context of malnourishment and alcoholism. Classically, this
      demyelinating disease arises from the rapid correction of hyponatraemia,
      resulting in profound neurological deficits such as spastic quadraplegia and
      pseudobulbar palsy. Diagnosis is usually made on the presence of a symmetrical,
      centralized and well-circumscribed lesion in the pens, seen on MRI. Extrapontine
      lesions have also been described, frequently affecting the midbrain, thalamus,
      cerebellum and rarely extends to the medulla. We present a case of a 41 year old
      lady who presented with acute neurological deterioration, with physical signs to
      suggest a disease process involving the whole brainstem. However, MRI brain
      showed a lesion similar to that found in CPM, at the junction of the pons and
      medulla.

PMID- 17432815
TI  - Autoimmune haemolytic anaemia due to Omeprazole.
AB  - A 72-year-old lady who was prescribed Omeprazole for gastroesophageal reflux
      developed an allergic reaction within two days, which manifested initially as a
      generalised rash and marked eosinophilia. This was followed by a fall in
      haemoglobin without any obvious bleeding. Investigations pointed to drug related
      intravascular haemolysis as the cause. She made an uneventful recovery after
      omitting Omeprazole and treatment with steroids. Omeprazole should be considered
      amongst other recognised causes of drug-induced haemolysis

PMID- 17432816
TI  - Gianotti-Crosti syndrome following meningococcal septicaemia.

PMID- 17432817
TI  - Thoracic outlet syndrome secondary to first rib anomaly: the value of multi-slice
      CT in diagnosis and surgical planning.

PMID- 17432818
TI  - What is common sense?

PMID- 17432819
TI  - Bacteriology of discharging ears.

PMID- 17432820
TI  - Inhibition of angiogenesis by the antifungal drug itraconazole.
AB  - Angiogenesis, the formation of new blood vessels, is implicated in a number of
      important human diseases, including cancer, diabetic retinopathy, and rheumatoid
      arthritis. To identify clinically useful angiogenesis inhibitors, we assembled
      and screened a library of mostly Food and Drug Administration-approved drugs for
      inhibitors of human endothelial cell proliferation. One of the most promising and
      unexpected hits was itraconazole, a known antifungal drug. Itraconazole inhibits
      endothelial cell cycle progression at the G1 phase in vitro and blocks vascular
      endothelial growth factor/basic fibroblast growth factor-dependent angiogenesis
      in vivo. In attempts to delineate the mechanism of action of itraconazole, we
      found that human lanosterol 14alpha-demethylase (14DM) is essential for
      endothelial cell proliferation and may partially mediate the inhibition of
      endothelial cells by itraconazole. Together, these findings suggest that
      itraconazole has the potential to serve as an antiangiogenic drug and that
      lanosterol 14DM is a promising new target for discovering new angiogenesis
      inhibitors.

PMID- 17432821
TI  - Activating B cell signaling with defined multivalent ligands.
AB  - Depending on the stimuli they encounter, B lymphocytes engage in signaling events
      that lead to immunity or tolerance. Both responses are mediated through antigen
      interactions with the B cell antigen receptor (BCR). Antigen valency is thought
      to be an important parameter in B cell signaling, but systematic studies are
      lacking. To explore this issue, we synthesized multivalent ligands of defined
      valencies using the ring-opening metathesis polymerization (ROMP). When mice are
      injected with multivalent antigens generated by ROMP, only those of high
      valencies elicit antibody production. These results indicate that ligands
      synthesized by ROMP can activate immune responses in vivo. All of the multivalent
      antigens tested activate signaling through the BCR. The ability of antigens to
      cluster the BCR, promote its localization to membrane microdomains, and augment
      intracellular Ca2+ concentration increases as a function of antigen valency. In
      contrast, no differences in BCR internalization were detected. Our results
      indicate that differences in the antigenicity of BCR ligands are related to their
      ability to elicit increases in intracellular Ca2+ concentration. Finally, we
      observed that unligated BCRs cluster with BCRs engaged by multivalent ligands, a
      result that suggests that signals mediated by the BCR are amplified through
      receptor arrays. Our data suggest a link between the mechanisms underlying signal
      initiation by receptors that must respond with high sensitivity.

PMID- 17432822
TI  - Novel inositol phospholipid headgroup surrogate crystallized in the pleckstrin
      homology domain of protein kinase Balpha.
AB  - Protein kinase B (PKB/Akt) plays a key role in cell signaling. The PH domain of
      PKB binds phosphatidylinositol 3,4,5-trisphosphate translocating PKB to the
      plasma membrane for activation by 3-phosphoinositide-dependent protein kinase 1.
      The crystal structure of the headgroup inositol 1,3,4,5-tetrakisphosphate
      Ins(1,3,4,5)P4-PKB complex facilitates in silico ligand design. The novel achiral
      analogue benzene 1,2,3,4-tetrakisphosphate (Bz(1,2,3,4)P4) possesses phosphate
      regiochemistry different from that of Ins(1,3,4,5)P4 and surprisingly binds with
      similar affinity as the natural headgroup. Bz(1,2,3,4)P4 co-crystallizes with the
      PKBalpha PH domain in a fashion also predictable in silico. The 2-phosphate of
      Bz(1,2,3,4)P4 does not interact with any residue, and the D5-phosphate of
      Ins(1,3,4,5)P4 is not mimicked by Bz(1,2,3,4)P4. Bz(1,2,3,4)P4 is an example of a
      simple inositol phosphate surrogate crystallized in a protein, and this approach
      could be applied to design modulators of inositol polyphosphate binding proteins.

PMID- 17432823
TI  - Design and creation of new nanomaterials for therapeutic RNAi.
AB  - RNA interference is an evolutionarily conserved gene-silencing phenomenon that
      shows great promise for developing new therapies. However, the development of
      small interfering RNA (siRNA)-based therapies needs to overcome two barriers and
      be able to (i) identify chemically stable and effective siRNA sequences and (ii)
      efficiently silence target genes with siRNA doses that will be clinically
      feasible in humans. Here, we report the design and creation of interfering
      nanoparticles (iNOPs) as new systemic gene-silencing agents. iNOPs have two
      subunits: (i) a well-defined functionalized lipid nanoparticle as a delivery
      agent and (ii) a chemically modified siRNA for sustained silencing in vivo. When
      we injected iNOPs containing only 1-5 mg kg(-1) siRNA into mice, an endogenous
      gene for apolipoprotein B (apoB) was silenced in liver, plasma levels of apoB
      decreased, and total plasma cholesterol was lowered. iNOP treatment was nontoxic
      and did not induce an immune response. Our results show that these iNOPs can
      silence disease-related endogenous genes in clinically acceptable and
      therapeutically affordable doses.

PMID- 17432824
TI  - Immobilization of aprotinin to fibrinogen as a novel method for controlling
      degradation of fibrin gels.
AB  - The goal of this work was to demonstrate that aprotinin conjugated to fibrinogen
      could (1) maintain its function and (2) control fibrin degradation. Using the
      chick chorioallantoic membrane (CAM) assay, we found that blood vessels did not
      directly invade fibrin constructs containing immobilized fibroblast growth factor
      2. Because the fibrin quickly degraded within approximately 5 days, we
      hypothesized that controlling fibrinolysis may improve direct blood vessel
      invasion. Aprotinin, a protease inhibitor typically added to slow fibrinolysis,
      is a small protein and can diffuse out of the gel resulting in the loss of
      fibrinolysis protection. Therefore, using a novel synthesis strategy, aprotinin
      and a fluorescent reporter, Cy3, were chemically conjugated to fibrinogen. In
      vitro microplate absorbance assays showed that the conjugated aprotinin was able
      to inhibit plasmin-mediated fibrin degradation and that its activity was
      comparable to equimolar levels of soluble, nonconjugated aprotinin. Additionally,
      we found that fibrinolysis rates could be tuned by varying the level of
      conjugated aprotinin within the gel. The conjugated aprotinin also demonstrated
      functionality in vivo. In the chick CAM assay, fibrin gels containing conjugated
      aprotinin were approximately 5 times larger than gels containing soluble
      aprotinin after 4 days. Also, in support of our hypothesis, we found that
      immobilized aprotinin within fibrin gels demonstrated substantial blood vessel
      invasion.

PMID- 17432825
TI  - Biotinylated photocleavable polyethylenimine: capture and triggered release of
      nucleic acids from solid supports.
AB  - A biotinylated photocleavable polyethylenimine (B-PC-PEI) was designed and
      synthesized for the capture and controlled release of nucleic acids from solid
      supports. B-PC-PEI was synthesized via a three-step reaction process and verified
      by 1H NMR and mass spectrometry. In aqueous solution, the o-nitrobenzyl group
      within B-PC-PEI was efficiently cleaved by 5 min of 365 nm light exposure from a
      distance of 20 cm (9 mW/cm2). When coupled to streptavidin-coated beads, the PEI
      domain of Cy5-labeled B-PC-PEI was released by 365 nm light exposure. In
      contrast, a Cy5-labeled biotinylated PEI (B-PEI) was used as a control and
      negligible fluorescence loss was observed. Cy5-labeled siRNA was
      electrostatically captured to streptavidin-coated beads preabsorbed with B-PC-PEI
      or B-PEI, and flow cytometry demonstrated significant loss of fluorescence from
      the bead surface after 5 min of light exposure only for B-PC-PEI, demonstrating
      controlled release of siRNA from the bead surface. Finally, the release of the
      Cy5-labeled siRNA into the supernatant was quantified. The release of Cy5-siRNA
      into the supernatant was significantly greater after 5 min of light exposure for
      B-PC-PEI/streptavidin beads compared to 0 min exposure and remained unchanged for
      B-PEI/streptavidin beads. B-PC-PEI facilitates capture and triggered release of
      surface-tethered nucleic acids with light exposure and is fully compatible with
      streptavidin-based applications.

PMID- 17432826
TI  - N,N-dimethylsphingosine-coumarin: synthesis, chemical characterization, and
      biological evaluation.
AB  - Coumarin derivatives of N,N-dimethylsphingosine (DMSP) were prepared and
      chemically characterized. They were apparently biologically equivalent to DMSP in
      terms of tumor cell cytotoxicity and were used to establish the rapid
      mitochondrial localization of this sphingolipid in tumor cells, followed closely
      by its marked reduction of mitochondrial membrane potential.

PMID- 17432827
TI  - Flow photolysis for spatiotemporal stimulation of single cells.
AB  - Quantitative studies of cellular systems require experimental techniques that can
      expose single cells to well-controlled chemical stimuli with high spatiotemporal
      resolution. Here, we combine microfluidic techniques with the photochemical
      release of caged signaling molecules to generate tailored stimuli on the length
      scale of individual cells with subsecond switching times. We exemplify this
      flexible approach by initiating membrane translocation of fluorescent fusion
      proteins in chemotactic Dictyostelium discoideum cells.

PMID- 17432828
TI  - Compact ambient pressure pyroelectric ion source for mass spectrometry.
AB  - We present the construction and implementation of a compact, low-power ambient
      pressure pyroelectric ionization source. The source comprises a z-cut lithium
      niobate or lithium tantalate crystal with an attached resistive heater mounted in
      front of the atmospheric pressure inlet of an ion trap mass spectrometer.
      Positive and negative ion formation alternately results from thermally cycling
      the crystal over a narrow temperature range. Ionization of 1,1,1,3,3,3-hexafluoro
      2-propanol or benzoic acid results in the observation of the singly deprotonated
      species and their clusters in the negative ion mass spectrum. Ionization of
      triethylamine or triphenylamine with the source results in observation of the
      corresponding singly protonated species of each in the positive ion mass
      spectrum. Although processes in which ion formation occurs directly on the highly
      charged crystal surface may contribute to the observed signal, ion formation
      appears to result mainly from electrical discharges occurring on the surface of
      the crystal, from one z face to another. This dielectric breakdown originates
      from the high electric fields generated at the surface of pyroelectric crystals
      when they are thermally cycled by as little as 30 K from ambient temperature. Ion
      formation is largely unaffected by contamination of the crystal faces. This
      robust source might prove particularly useful in applications where unattended
      operation in harsh environments, long service lifetimes, and durability are
      desirable characteristics.

PMID- 17432830
TI  - Dynamics of light-induced conformational changes of the phoborhodopsin/transducer
      complex formed in the n-dodecyl beta-D-maltoside micelle.
AB  - A complex of photoreceptor phoborhodopsin (ppR; also called sensory rhodopsin II)
      and its cognate halobacterial transducer II (pHtrII) existing in the plasma
      membrane mediates the light signal to the cytoplasm in the earliest step of
      negative phototaxis in Natronomonas pharaonis. We have investigated the dynamics
      of the light-induced conformational changes of the ppR/pHtrII(1-159) complex
      formed in the presence of 0.1% n-dodecyl beta-d-maltoside (DDM) by a fluorescence
      resonance energy transfer (FRET) based method. Fluorescence donor and acceptor
      dyes were linked to cysteine residues genetically introduced at given positions
      in pHtrII and ppR. The light-induced FRET efficiency changes for various pairs of
      dye-labeled cysteine residues were determined to examine dynamics of movements of
      given residues in the transmembrane and the linker region including the HAMP
      domain in pHtrII induced by photoexcitation of ppR. Upon flash excitation of ppR,
      FRET efficiency changed depending on pairs of the labeled cysteine residues. The
      distances between V185 in ppR and the five given residues (102 through 141) in
      the pHtrII linker region estimated from the FRET efficiency increased by 0.3-0.8
      A; on the other hand, the distances between S31 in ppR and the five residues in
      pHtrII decreased. The changes arose within 70 ms (the dead time of instrument)
      and decayed at a rate of 1.1 +/- 0.2 s. Azide significantly increased the decay
      rate of light-induced FRET efficiency changes by accelerating the decay of the M
      state of ppR. The decay rate of FRET efficiency changes coincided with the rate
      of recovery of the ppR to the initial state but not the decay of the M state. We
      conclude that the light-induced conformational change of pHtrII occurs before, at
      the formation or during the M state, and its relaxation is coupled tightly with
      the decay of the O state of ppR in the 1:1 complex formed in the DDM micelle.

PMID- 17432831
TI  - Regulation of energy dissipation in photosystem I by the redox state of the
      plastoquinone pool.
AB  - The effect of exogenous plastoquinone (PQ) on the different deexcitation pathways
      of photosystem I (PSI) was investigated. Addition of oxidized decyl-plastoquinone
      (dPQ) and PQ-2 strongly quenched the chlorophyll (Chl) emission spectra of PSI
      submembrane fractions over all wavelengths. This quenching increased with the
      concentration of exogenous PQ added and followed the modified Stern-Volmer law.
      The Stern-Volmer constants found for dPQ and PQ-2 were 1.25 x 10(6) M-1 and 0.55
      x 10(6) M-1, respectively, and the fraction of fluorescence accessible to the
      quencher was 0.7 for both exogenous PQ. dPQ and PQ-2 also retarded the P700
      photooxidation measured under limiting actinic light irradiances. Photoacoustic
      measurements showed that addition of dPQ increased the heat dissipation and
      decreased the photochemical capacity of PSI. From these results, exogenous
      oxidized PQ were shown to efficiently quench the Chl excited state in the PSI
      antenna and change the balance between Chl deexcitation pathways. Moreover,
      reduction of the endogenous PQ pool in whole thylakoid membranes by NADPH
      increased PSI fluorescence by 65%, indicating the importance of the redox state
      of the PQ pool on PSI energy dissipation.

PMID- 17432829
TI  - Lesion specificity in the base excision repair enzyme hNeil1: modeling and
      dynamics studies.
AB  - Base excision repair (BER) is the major pathway employed to excise oxidized DNA
      lesions. Human Neil1, a versatile glycosylase in the BER pathway, repairs a
      diverse array of oxidative lesions; however, the most prevalent, 8-oxo-7,8
      dihydroguanine (8-oxoG), is only weakly excised. The structural origin of
      hNeil1's ability to repair a variety of lesions but not 8-oxoG is a model system
      for connecting enzyme structure and lesion-recognition specificity. To elucidate
      structural properties determining hNeil1's substrate specificities, we have
      investigated it in complex with two pairs of representative well-repaired
      substrates: the R- and S-spiroiminodihydantoin (Sp) stereoisomers, nonplanar
      further oxidation products of guanine, and the 5R,6S- and 5S,6R-thymine glycol
      (Tg) stereoisomers, the most prevalent oxidative lesions of thymine. We also
      investigate the poorly repaired 8-oxoG. We employed molecular modeling and 10 ns
      molecular dynamics (MD) simulations. The results of our investigations provide
      structural explanations for the ability of hNeil1 to excise a variety of
      oxidative lesions: they possess common chemical features, namely, a pyrimidine
      like ring and shared hydrogen bond donor-acceptor properties, which allow the
      lesions to fit well in the binding pocket, which is somewhat flexible. However,
      the planar 8-oxoG is not as well accommodated in the shallow and comparatively
      cramped recognition pocket; it has fewer hydrogen bonding interactions with the
      enzyme and a solvent exposed six-membered ring, consistent with its poor repair
      susceptibility by this enzyme.

PMID- 17432832
TI  - Kinetic mechanism of ligand binding in human ileal bile acid binding protein as
      determined by stopped-flow fluorescence analysis.
AB  - Cooperative ligand binding to human ileal bile acid binding protein (I-BABP) was
      studied using the stopped-flow fluorescence technique. The kinetic data obtained
      for wild-type protein are in agreement with a four-step mechanism where after a
      fast conformational change on the millisecond time scale, the ligands bind in a
      sequential manner, followed by another, slow conformational change on the time
      scale of seconds. This last step is more pronounced in the case of glycocholate
      (GCA), the bile salt that binds with high positive cooperativity and is absent in
      mutant I-BABP proteins that lack positive cooperativity in their bile salt
      binding. These results suggest that positive cooperativity in human I-BABP is
      related to a slow conformational change of the protein, which occurs after the
      second binding step. Analogous to that in the intestinal fatty acid binding
      protein (I-FABP), we hypothesize that ligand binding in I-BABP is linked to a
      disorder-order transition between an open and a closed form of the protein.

PMID- 17432833
TI  - Functional characterization of monomeric photosystem II core preparations from
      Thermosynechococcus elongatus with or without the Psb27 protein.
AB  - Two monomeric fractions of photosystem II (PS II) core pacticles from the
      thermophilic cyanobacterium Thermosynechococcus elongatus have been investigated
      using flash-induced variable fluorescence kinetics and EPR spectroscopy. One
      fraction was highly active in oxygen evolution and contained the extrinsic
      protein subunits PsbO, PsbU, and PsbV. The other monomeric fraction lacked oxygen
      evolving activity as well as the three extrinsic subunits, but the luminally
      located, extrinsic Psb27 lipoprotein was present. In the monomeric fraction with
      bound Psb27, flash-induced variable fluorescence showed an absence of oxidizable
      Mn on the donor side of PS II and impaired forward electron transfer from the
      primary quinone acceptor, QA. These results were confirmed with EPR spectroscopy
      by the absence of the "split S1" interaction signal from YZ* and the CaMn4
      cluster and by the absence of the S2-state multiline signal. A different protein
      composition on the donor side of PS II monomers with Psb27 was also supported by
      the lack of an EPR signal from cytochrome c550 (in the PsbV subunit). In
      addition, we did not observe any oxidation of cytochrome b559 at low temperature
      in this fraction. The presence of Psb27 and the absence of the CaMn4 cluster did
      not affect the protein matrix around YD or the acceptor side quinones as can be
      judged from the appearance of the corresponding EPR signals. The diminished
      electron transport capabilities on both the donor and the acceptor side of PS II
      when Psb27 is present give further indications that this PS II complex is
      involved in the earlier steps of the PS II repair cycle.

PMID- 17432834
TI  - Effects of chain length on the rates of C-C bond dissociation in linear alkanes
      and polyethylene.
AB  - Molecular dynamics modeling of C-C bond dissociation is performed for a series of
      linear alkanes and polyethylene macromolecules with the chain lengths ranging
      from one to a thousand constituent ethylene monomers (PE-1-PE-1000). The rate
      constants obtained in molecular dynamics calculations are compared with those
      determined using variational transition state theory with the same potential
      energy surface. The results of simulations demonstrate a significant accelerating
      effect of chain length on the rates of C-C bond scission. Per-bond rate constant
      values increase with the increasing chain length, up to an order of magnitude, in
      the sequence of linear alkanes from PE-1 (ethane) to PE-5 (decane); this
      dependence becomes saturated for longer chain lengths. Stiffening the potentials
      of bending and especially the torsional degrees of freedom diminishes the
      accelerating effect of chain length, while constraining the bond distances for
      all C-C bonds except the one undergoing dissociation has no effect. The results
      of the calculations are compared with existing experimental data on the
      dependences of the rates of thermal decomposition of linear alkanes on the alkane
      chain length.

PMID- 17432835
TI  - Reaction of acetaldehyde with Ni+: an extended theoretical study of the
      decarbonylation mechanism of acetaldehyde by first-row transition metal ions.
AB  - We report herein a theoretical study of the reaction of acetaldehyde with Ni+ as
      an extension of our two recent papers on the decarbonylation of acetaldehyde by
      late first-row transition metal ions [Zhao, Zhang, Guo, Wu, Lu Chem. Phys. Lett.
      2005, 414, 28; Zhao, Guo, Zhang, Wu, Lu ChemPhysChem 2006, 7, 1345]. Geometries
      of all the stationary points involved in the reaction have been fully optimized
      at the B3LYP/6-311+G(2df,2pd) level and the decarbonylation mechanism is analyzed
      in terms of the topology of potential energy surface. Combining with the previous
      studies, it is found that for the Cr+, Co+, and 4Fe+ mediated systems
      decarbonylation of CH3CHO only takes place via C-C activation, and aldehyde C-H
      activation is unlikely to be important, whereas both C-C and aldehyde C-H
      activations by Ni+ and 6Fe+ could result in the decarbonylation of CH3CHO, where
      hydride-containing species M+(H)(CO)(CH3) is found to be a common minimum along
      the reaction pathways.

PMID- 17432836
TI  - Clusters of hydrated methane sulfonic acid CH3SO3H.(H2O)n (n = 1-5): a
      theoretical study.
AB  - Ab initio and density functional methods have been used to examine the structures
      and energetics of the hydrated clusters of methane sulfonic acid (MSA),
      CH3SO3H.(H2O)n (n = 1-5). For small clusters with one or two water molecules, the
      most stable clusters have strong cyclic hydrogen bonds between the proton of OH
      group in MSA and the water molecules. With three or more water molecules, the
      proton transfer from MSA to water becomes possible, forming ion-pair structures
      between CH3SO3- and H3O+ moieties. For MSA.(H2O)3, the energy difference between
      the most stable ion pair and neutral structures are less than 1 kJ/mol, thus
      coexistence of neutral and ion-pair isomers are expected. For larger clusters
      with four and five water molecules, the ion-pair isomers are more stable (>10
      kJ/mol) than the neutral ones; thus, proton transfer takes place. The ion-pair
      clusters can have direct hydrogen bond between CH3SO3- and H3O+ or indirect one
      through water molecule. For MSA.(H2O)5, the energy difference between ion pairs
      with direct and indirect hydrogen bonds are less than 1 kJ/mol; namely, the
      charge separation and acid ionization is energetically possible. The calculated
      IR spectra of stable isomers of MSA.(H2O)n clusters clearly demonstrate the
      significant red shift of OH stretching of MSA and hydrogen-bonded OH stretching
      of water molecules as the size of cluster increases.

PMID- 17432837
TI  - Influence of metal cations on the intramolecular hydrogen-bonding network and pKa
      in phosphorylated compounds.
AB  - The binding of the most common metal cations of cytoplasm (Li+, Na+, K+, Mg2+ and
      Ca2+) to a model molecule having an intramolecular hydrogen-bonding network, myo
      inositol-2-monophosphate, was studied using first principles. A strong
      correlation between the conformation of metal inositol phosphate complexes with
      the type of metal cation, degree of deprotonation state, and the surrounding
      environment has been observed. On the basis of the hydrogen-bonding network
      analysis of the cation-phosphate complexes (Mn+-Ins(2)P1), the alkali cations
      show little effect on the conformational preference while the conformational
      preference for the binding of the alkaline earth cations is pH-dependent and
      solvent-dependent. For example, these calculations predict that Mg2+-Ins(2)P1(0)
      and Mg2+-Ins(2)P1(2-) favor the 1a/5e form while Mg2+-Ins(2)P1(1-) favors the
      5a/1e conformation. The Ca2+-Ins(2)P1(2-) complex prefers the 1a/5e conformation
      in the gas phase and in a nonpolar protein environment, but inverts to the 5a/1e
      conformation upon entering the polar aqueous phase. The binding affinities of the
      cations and the pK(a) values for the cation-phosphate complexes are derived from
      thermodynamical analysis.

PMID- 17432838
TI  - Spin chemical control of photoinduced electron-transfer processes in
      ruthenium(II)-trisbipyridine-based supramolecular triads: 2. The effect of
      oxygen, sulfur, and selenium as heteroatom in the azine donor.
AB  - Nanosecond time-resolved absorption studies in a magnetic field ranging from 0 to
      2.0 T have been performed on a series of covalently linked donor(PXZ)
      Ru(bipyridine)3-acceptor(diquat) complexes (D-C2+-A2+). In the PXZ moiety, the
      heteroatom (X = O (oxygen), T (sulfur), and S (selenium)) is systematically
      varied to study spin-orbit coupling effects. On the nanosecond time scale, the
      first detectable photoinduced electron-transfer product after exciting the
      chromophore C2+ is the charge-separated (CS) state, D+-C2+-A+, where an electron
      of the PXZ moiety, D, has been transferred to the diquat moiety, A2+. The
      magnetic-field-dependent kinetic behavior of charge recombination
      (monoexponential at 0 T progressing to biexponential for all three complexes with
      increasing field) can be quantitatively modeled by the radical pair relaxation
      mechanism assuming creation of the CS state with pure triplet spin correlation
      (3CS). Magnetic-field-independent contributions to the rate constant kr of T+/- -
      > (T0,S) relaxation are about 4.5 x 10(5) s-1 for DCA-POZ and -PTZ (due to a
      vibrational mechanism) and 3.5 x 10(6) s-1 for DCA-PSZ (due to spin rotational
      mechanism). Recombination to the singlet ground state is allowed only from the
      1CS spin level; spin-forbidden recombination from 3CS seems negligible even for
      DCA-PSZ. The field dependence of kr (field-dependent recombination) can be
      decomposed into the contributions of various relaxation mechanisms. For all
      compounds, the electron spin dipolar coupling relaxation mechanism dominates the
      field dependence of tau(slow) at fields up to about 100 mT. Spin relaxation due
      to the g-tensor anisotropy relaxation mechanism accounts for the field dependence
      of tau(slow) for DCA-PSZ at high fields. For the underlying stochastic process, a
      very short correlation time of 2 ps has to be assumed, which is tentatively
      assigned to a flapping motion of the central, nonplanar ring in PSZ. Finally, it
      has been confirmed by paramagnetic quenching (here Heisenberg exchange)
      experiments of the magnetic-field effects with TEMPO that all magnetic-field
      dependencies observed with the present DCA-PSZ systems are indeed due to the
      magnetic-field dependence of spin relaxation.

PMID- 17432839
TI  - Experimental and computational studies of the phenyl radical reaction with
      allene.
AB  - The kinetics for the gas-phase reaction of phenyl radicals with allene has been
      measured by cavity ring-down spectrometry (CRDS), and the mechanism and initial
      product branching have been elucidated with the help of quantum-chemical
      calculations. The absolute rate constant measured by the CRDS technique can be
      expressed by the following Arrhenius equation: kallene (T=301-421 K)=(4.07+/
      0.38)x10(11) exp[-(1865+/-85)/T] cm3 mol(-1) s(-1). Theoretical calculations,
      employing high level G2M energetic and IRCMax(RCCSD(T)//B3LYP-DFT) molecular
      parameters, indicate that under our experimental conditions the most preferable
      reaction channel is the addition of phenyl radicals to the terminal carbon atoms
      in allene. Predicted total rate constants agree with the experimental values
      within 40%. Calculated total and branching rate constants are provided for high-T
      kinetic modeling.

PMID- 17432840
TI  - Quasi-classical trajectory study of the F + CD4 reaction dynamics.
AB  - To analyze the F + CD4 gas-phase abstraction reaction, an exhaustive state-to
      state dynamics study was performed. Quasi-classical trajectory (QCT)
      calculations, including corrections to avoid zero-point energy leakage along the
      trajectories, were used on an analytical potential energy surface (PES-2006)
      recently developed by our group for collision energies in the range 0.3-6.0 kcal
      mol-1. While the CD3 coproduct appears vibrationally and rotationally cold, in
      agreement with experiment, most of the available energy appears as FD(nu')
      product vibrational energy, peaking at nu' = 3, one unit colder than experiment.
      The excitation function reproduces experiment, with the maximum contribution from
      the most populated FD(nu' = 3) level. The state-specific scattering distributions
      at different collision energies also reproduce the experimental behavior, with a
      clear propensity toward forward scattering, this tendency increasing with the
      energy. These dynamics results show the capacity of the PES-2006 surface to
      correctly describe the title reaction.

PMID- 17432841
TI  - Smallest peptoids with antiproliferative activity on human neoplastic cells.
AB  - Libraries of new, small peptoid monomers and dipeptoids were synthesized and
      assayed for antiproliferative activity against representative human neoplastic
      cell lines. The C-terminal N-alkyl amide peptoids are cytotoxic and are the
      smallest peptoids reported to have such activity. These compounds were
      conveniently synthesized on a BAL resin. Owing to their structure, the peptoids
      did not suffer from DKP formation, a problematic side reaction typically observed
      in peptide and peptoid synthesis.

PMID- 17432842
TI  - Target-based approach to inhibitors of histone arginine methyltransferases.
AB  - Lysine and arginine methyltransferases participate in the post-translational
      modification of histones and regulate key cellular functions. So far only one
      arginine methyltransferase inhibitor discovered by random screening was
      available. We present the first target-based approach to protein arginine
      methyltransferase (PRMT) inhibitors. Homology models of human and Aspergillus
      nidulans PRMT1 were generated from available X-ray structures of rat PRMTs. The
      NCI diversity set was filtered by a target-based virtual screening to identify
      PRMT inhibitors. Employing a fungal PRMT for screening and a human enzyme for
      validation, we have identified seven inhibitors of PRMTs in vitro. Hit validation
      was achieved for two new inhibitors by antibody mediated detection of histone
      hypomethylation as well as Western blotting in cancer cells. Functional activity
      was proven by an observed block of estrogen receptor activation. Thus, valuable
      chemical tools and potential drug candidates could be identified.

PMID- 17432844
TI  - Density functional study of lithium hexamethyldisilazide (LiHMDS) complexes:
      effects of solvation and aggregation.
AB  - The title compound, lithium hexamethyldisilazide (LiHMDS), has been studied using
      modern quantum-chemical methods in the form of the B3LYP approach. Monomers,
      dimers, trimers, and tetramers, microsolvated with up to four THF molecules have
      been considered. The choice of model complex is seen to be important-for
      instance, the simpler water molecule is shown to be an inappropriate substitute
      for the THF solvent. Calculated lithium NMR shieldings are reported, but by
      themselves, they seem to be insufficient for unequivocal assignments of the
      different species. The energetics of aggregation and solvation have been studied.
      Temperature effects are seen to be important, and the degrees of solvation and
      aggregation are higher at 0 K than at 298 K. The highest degree of THF solvation
      for the monomer and dimer is found to be three (0 K) and two (298 K),
      respectively. The highest possible degree of aggregation for unsolvated LiHMDS is
      four. However, in nonpolar solvents, formation of the LiHDMS dimer from the
      trimer is thermodynamically preferred. The pathway is likely to involve an
      intermediate tetramer. In THF solution, di-solvated monomers and dimers are the
      most likely species.

PMID- 17432843
TI  - Design, synthesis, and X-ray structure of potent memapsin 2 (beta-secretase)
      inhibitors with isophthalamide derivatives as the P2-P3-ligands.
AB  - Structure-based design and synthesis of a number of potent and selective memapsin
      2 inhibitors are described. These inhibitors were designed based upon the X-ray
      structure of memapsin 2-bound inhibitor 3 that incorporates methylsulfonyl
      alanine as the P2-ligand and a substituted pyrazole as the P3-ligand. Of
      particular importance, we examined the ability of the substituted isophthalic
      acid amide derivative to mimic the key interactions in the S2-S3 regions of the
      enzyme active sites of 3-bound memapsin 2. We investigated various substituted
      phenylethyl, alpha-methylbenzyl, and oxazolylmethyl groups as the P3-ligands. A
      number of inhibitors exhibited very potent inhibitory activity against mempasin 2
      and good selectivity against memapsin 1. Inhibitor 5d has shown low nanomolar
      enzyme inhibitory potency (Ki=1.1 nM) and very good cellular inhibitory activity
      (IC50=39 nM). Furthermore, in a preliminary study, inhibitor 5d has shown 30%
      reduction of Abeta40 production in transgenic mice after a single intraperitoneal
      administration (8 mg/kg). A protein-ligand X-ray crystal structure of 5d-bound
      memapsin 2 provided vital molecular insight that can serve as an important guide
      to further design of novel inhibitors.

PMID- 17432845
TI  - Systematics and anomalies in rare earth/aluminum bromide vapor complexes:
      thermodynamic properties of the vapor complexes LnAl3Br12 from Ln = Sc to Ln =
      Lu.
AB  - Systematics and anomalies in the rare earth/aluminum bromide vapor complexes have
      been investigated by the phase equilibrium-quenching experiments. The
      measurements suggest that the LnAl3Br12 complexes are the predominant vapor
      complexes for the 16 rare earth elements Ln = Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd,
      Tb, Dy, Ho, Er, Tm, Yb, and Lu in the temperature range 601-833 K and pressure
      range 0.01-0.22 MPa, which is different from the rare earth/aluminum chloride
      systems, where the predominant vapor complexes are LnAl3Cl12 from Ln = La to Ln =
      Lu, but LnAl2Cl9 for Ln = Sc and Y are roughly in the same ranges, which
      indicates the importance of the halogen anion radius on the rare earth vapor
      complex formation. In the temperature and pressure ranges, gaseous Al2Br6 and
      AlBr3 are dominant species and the molar fraction of LnAl3Br12 is normally less
      than 0.01. Thermodynamic functions of the reactions LnBr3(s) + (3/2)Al2Br6(g) =
      LnAl3Br12(g) were calculated from the measurements for the 16 rare earth elements
      and then smoothly interpolated for the radioelement Ln = Pm. The standard molar
      enthalpies and standard molar entropies show significant Gd divergences from
      LaAl3Br12 to LuAl3Br12 when plotted as functions of the rare earth atomic number.
      They also suggest nearly linear manner for ScAl3Br12, LuAl3Br12, YAl3Br12, and
      LaAl3Br12 when plotted as functions of the rare earth ionic radius.

PMID- 17432846
TI  - Molecular tectonics of mixed-ligand metal-organic frameworks: positional isomeric
      effect, metal-directed assembly, and structural diversification.
AB  - A series of nine mixed-ligand metal-organic frameworks (MOFs) have been prepared
      by the combination of a bent dipyridyl linker 4-amino-3,5-bis(4-pyridyl)-1,2,4
      triazole (bpt) and three benzenedicarboxylate isomers (pa = phthalate, ip =
      isophthalate, and tp = terephthalate), respectively, with different metal ions
      such as CoII, NiII, CuII, ZnII, and CdII. The framework structures of these
      neutral polymeric complexes have been determined by the X-ray single-crystal
      diffraction technique. Structural analysis reveals that the benzenedicarboxylate
      isomers display versatile coordination modes to manage the metal ions to form 1-D
      chain or ribbon arrays, which are further extended via the exo-bidentate bpt
      connectors to give rise to a variety of coordination networks, such as a simple
      (4,4) layer, 2-D double layer with decorated (4,4) topology, 2-D layer with
      decorated (3,6) topology, 2-D bilayer with 82.10 topology (2-fold
      interpenetration), 3-D polythreaded architecture (1-D + 2-D), and 2-fold
      interpenetrating porous lattice of (4,4) layers. The accessorial secondary
      interactions such as hydrogen bonding and/or aromatic stacking are also helpful
      for the extension and stabilization of the final supramolecular aggregates. This
      work evidently indicates that the isomeric effect of the anionic
      benzenedicarboxylate is significant in the construction of these network
      structures, which are also well regulated by the metal centers. The ZnII and CdII
      MOFs exhibit strong solid-state luminescence emissions at room temperature, which
      originate differently from intraligand transition or ligand-to-metal charge
      transfer. Thermal stability of these crystalline materials has been explored by
      thermogravimetric analysis of mass loss. The 3-D host frameworks of MOFs 8 and 9
      show similar porous cavities, and their desorption/adsorption behaviors of guest
      solvents have also been investigated.

PMID- 17432847
TI  - Two-dimensional heisenberg antiferromagnets: syntheses, X-ray structures, and
      magnetic behavior of [Cu(pz)2](ClO4)2, [Cu(pz)2](BF4)2, and [Cu(pz)2(NO3)](PF6).
AB  - We report on the syntheses, crystal structures, and magnetic susceptibilities of
      a family of copper pyrazine (pz)-based antiferromagnets with moderate in-plane
      magnetic exchange. These materials fall into two classes: monoclinic complexes
      [Cu(pz)2]A2 for A = ClO4 (1) or BF4 (2) and the tetragonal complex
      [Cu(pz)2(NO3)]PF6 (3). Compound 1 and its deuterated version [Cu(pz-d4)2](ClO4)2
      (1a) crystallize in the space group C2/m at room temperature with disordered
      perchlorate anions. For both 1 and 2, the C centering of the Cu(II), S = 1/2,
      site yields four equivalent nearest neighbors, producing layers of Cu(II) ions
      bridged by the pz molecules, which map onto a square magnetic lattice. The layers
      are offset such that Cu(II) ions lie above and below the holes of adjacent
      layers. Compound 3 crystallizes in the space group I4/mcm with a layer structure
      similar to those of 1 and 2 but with Cu(II) ions of adjacent layers stacked above
      each other and bridged by semicoordinate NO3- ions. The variable-temperature
      susceptibilities in these compounds approximate a two-dimensional Heisenberg
      antiferromagnet with J values within the layers of 17.5(3) K (1), 15.3(3) K (2),
      and 10.8(3) K (3). Ordering transitions are observed in the magnetic data at
      4.2(3) and 4.3(5) K for 1 and 2, respectively.

PMID- 17432848
TI  - Manganese(III,IV) and manganese(III) oxide clusters trapped by copper(II)
      complexes.
AB  - Reactions of quinquedentate Schiff base ligands with Mn and Cu ions afforded
      icosa- and hexadecanuclear mixed-metal clusters in which dinuclear CuII complexes
      trapped oxo-bridged [MnIII8MnIV4O12] and [MnIII6O6] cores, respectively. Maximum
      entropy method analysis for synchrotron X-ray diffraction data was used to
      determine the oxidation states of the Mn ions.

PMID- 17432850
TI  - Crystal structures and in-situ formation study of mayenite electrides.
AB  - Mayenite inorganic electrides are antizeolite nanoporous materials with variable
      electron concentration [Ca12Al14O32]2+ square5-deltaO1-delta2-e2delta- (0 < delta
      < or = 1), where square stands for empty sites. The oxymayenite crystal structure
      contains positively charged cages where loosely bounded oxide anions are located.
      These oxygens can be removed to yield electron-loaded materials in which the
      electrons behave like anions (electrides). Here, a new preparation method, which
      allows synthesizing powder mayenite electrides easily, is reported. Accurate
      structural data for the white (delta = 0) and green electride (delta
      approximately 0.5) are reported from joint Rietveld refinements of neutron and
      synchrotron X-ray powder diffraction data and also from single-crystal
      diffraction. The electride formation at high temperature under vacuum has been
      followed in-situ by neutron powder diffraction. The evolution of mayenite crystal
      structure, including the changes in the key occupation factor of the intracage
      oxide anions, is reported. Furthermore, the stability of mayenite framework in
      very low oxygen partial pressure conditions is also studied. It has been found
      that C12A7 decomposes, at 1373 K in reducing conditions, to give Ca5Al6O14 (C5A3)
      and Ca3Al2O6 (C3A). The kinetics of this transformation has also been studied.
      The fit of the transformed fraction to the classic Avrami-Erofe'ev equation gave
      an "Avrami exponent", n = 2, which indicates that nucleation is fast and the two
      dimensional linear growth of the new phases is likely to be the limiting factor.

PMID- 17432849
TI  - Synthesis and structures of bis(dithiolene)tungsten(IV,VI) thiolate and
      selenolate complexes: approaches to the active sites of molybdenum and tungsten
      formate dehydrogenases.
AB  - Formate dehydrogenases are molybdenum- or tungsten-containing enzymes that
      catalyze the oxidation of formate to carbon dioxide. Among the significant
      characteristics of the mononuclear active sites are coordination of two
      pyranopterindithiolene ligands and selenocysteinate to the metal in oxidation
      states IV-VI. The first detailed investigation of the synthesis and structures of
      bis(dithiolene)tungsten selenolate and analogous thiolate complexes of relevance
      to formate dehydrogenases has been undertaken. Some 17 complexes of the types
      [WIV(QR)(S2C2Me2)2]-, [WVIO(QR)(S2C2Me2)2]-, and [WVIS(QR)(S2C2Me2)2]- (Q = S,
      Se; R = tert-butyl, 1-adamantyl) and the desoxo species
      [WVI(SR)(OSiR'3)(S2C2Me2)2] (R' = Me, Ph) were prepared. Ten structures of
      representative members of these types were determined; WIV complexes are square
      pyramidal and WVI complexes are six-coordinate, with geometries intermediate
      between octahedral and trigonal-prismatic. Selenolate complexes are less stable
      than similar thiolate species; decomposition products were identified as [WV2(mu2
      Q)2(S2C2Me2)2]2- and [WIV,V2(mu2-Se)(S2C2Me2)4]-. The several
      [MoIV(QR)(S2C2Me2)2]- complexes prepared earlier and the tungsten compounds
      synthesized in this work form a family of molecules whose overall stereochemistry
      and metric features are those expected in the absence of protein structural
      constraints.

PMID- 17432851
TI  - Chemistry and stereochemistry of the interaction of the water-soluble phosphine
      [HO(CH2)3]3P with cinnamaldehyde in aqueous media.
AB  - To learn more about the bleaching action of pulps by (hydroxymethyl)phosphines,
      cinnamaldehyde was reacted with tris(3-hydroxypropyl)phosphine, [HO(CH2)3]3P
      (THPP), in aqueous solution at room temperature under argon. Self-condensation of
      the aldehyde into two isomeric products, 2-benzyl-5-phenyl-pent-2,4-dienal and 5
      phenyl-2-(phenylmethylene)-4-pentenal, is observed; this implies initial
      nucleophilic attack of the phosphine at the beta-carbon of the alpha,beta
      unsaturated aldehyde. Reaction in D2O gives the same products in which all but
      the phenyl and CHO protons are replaced by deuterons. NMR studies are consistent
      with carbanion formation and subsequent condensation of two phosphonium
      containing aldehyde moieties to generate the products with concomitant
      elimination of phosphine oxide. In D2O in the presence of HCl, THPP reversibly
      attacks the aldehyde-C atom to form the (alpha-hydroxy)phosphonium derivative
      [PhCH=C(H)CH(OD)PR3]Cl (where R=(CH2)3OD), which slowly converts into the
      deuterated bisphosphonium salt [R3PCH(Ph)CD(H)CH(OD)PR3]Cl2 via the deuterated
      monophosphonium salt [R3PCH(Ph)CD(H)CHO]Cl. The phosphonium intermediates and
      phosphonium products in this chemistry, although having up to three chiral carbon
      centers, are formed with high stereoselectivity just in enantiomeric forms. In
      acetone-H2O (1:1 v/v), a cross-condensation of cinnamaldehyde with acetone to
      give 6-phenyl-3,5-hexadien-2-one is promoted by THPP via generation of OH-.

PMID- 17432852
TI  - Magnesium borohydride complexed by tetramethylethylenediamine.
AB  - A complex of magnesium borohydride, Mg(BH4)2.Me2NC2H4NMe2, has been synthesized
      and structurally characterized. This monomer complex has a pseudotetrahedral
      geometry around the Mg atom with tridentate BH4 groups and short Mg...B
      distances.

PMID- 17432853
TI  - Reaction of cytochrome P450BM3 and peroxynitrite yields nitrosyl complex.
AB  - Peroxynitrite has come into the spotlight in recent years. Its effects on
      proteins have been implicated in several diseases such as acute lung injury,
      rheumatoid arthritis, implant rejection, artherosclerosis, Parkinson's disease,
      and Alzheimer's disease. Peroxynitrite is thought to inactivate a variety of
      proteins including thiolate-ligated heme proteins such as cytochrome P450 2B1 and
      PGI2 synthase, through the nitration of tyrosine residues. In previous studies it
      was reported that thiolate-ligated heme enzymes react with peroxynitrite to form
      a ferryl intermediate. In an effort to spectroscopically characterize this
      species in P450BM3, we discovered that the peroxynitrite-generated intermediate
      is not an FeIVoxo, but rather an iron-nitrosyl [FeNO]6 complex. We present
      density functional calculations as well as Mossbauer and stopped-flow
      spectroscopic characterizations of the peroxynitrite-generated intermediate in
      P450BM3.

PMID- 17432854
TI  - Total synthesis of lysobactin.
AB  - Antibiotic resistance has become a significant public health concern. Antibiotics
      that belong to new structural classes and manifest their biological activity via
      novel mechanisms are urgently needed. Lysobactin, a depsipeptide antibiotic has
      displayed very strong antibacterial activity against methicillin-resistant
      Staphylococcus aureus (MRSA) as well as vancomycin-resistant enterococci (VRE)
      with minimum inhibitory concentrations (MICs) ranging from 0.39 to 0.78
      microg/mL. The MIC values against VRE were more than 50-fold lower than those
      reported for vancomycin itself. Lysobactin was found to inhibit nascent
      peptidoglycan formation; however, this activity was not antagonized in the
      presence of N-acyl-L-Lys-D-Ala-D-Ala, the binding domain on the cell wall
      precursors that is utilized by vancomycin. Thus, lysobactin represents a
      promising agent for the treatment bacterial infections due to resistant
      pathogens. We describe a convergent synthesis of lysobactin that relies upon a
      highly efficient macrocyclization reaction to assemble the 28-membered cyclic
      depsipeptide. This synthesis provides the foundation for further study of the
      mode of action utilized by lysobactin and its analogues.

PMID- 17432855
TI  - Neutral fragment mass spectra via ambient thermal dissociation of peptide and
      protein ions.
AB  - A novel method for the fragmentation of peptide and protein ions at atmospheric
      pressure outside the mass spectrometer is described. Peptide/protein ions
      generated by electrosonic spray ionization (ESSI) are carried through a heated
      coiled metal tube where they fragment. Fragment ions of types a, b, and y are
      observed for peptides such as angiotensin II and bradykinin. In the case of
      phosphopeptides, informative b and y ions which preserve the labile phosphate
      groups are observed in the negative ion mode, which is potentially useful in the
      location of phosphorylation sites in proteins through chemical analysis of
      phosphopeptides. The thermal dissociation method extends to proteins such as
      ubiquitin and myoglobin, giving rise to y-type and other fragment ions. The most
      important feature of this method is that it also allows characterization of the
      neutral fragments arising from thermal dissociation by use of on-line corona
      discharge ionization. This neutral re-ionization experiment is much easier to
      perform outside the mass spectrometer than as conventionally done, in vacuum. It
      yields increased structural information from the resulting mass spectra in both
      the positive and the negative ion modes.

PMID- 17432856
TI  - Deciphering the structural transformations during nickel oxyhydroxide electrode
      operation.

PMID- 17432857
TI  - Chemical surface modification via radical C-C bond-forming reactions.

PMID- 17432858
TI  - Photochromism of diarylethene single molecules in polymer matrices.
AB  - Robust fluorescent photoswitching molecules, having perylene bisimide as the
      fluorescent unit and diarylethene as the switching unit, were prepared, and their
      photochromic reactions were measured at the single-molecule level in various
      polymer matrices. The histograms of the fluorescent on and off times were found
      to deviate from normal exponential distribution and showed a peak when the
      molecules are embedded in rigid polymer matrices, such as Zeonex or poly(methyl
      methacrylate) (PMMA). In soft polymer matrices, such as poly(n-buthyl
      methacrylate) (PnBMA), exponential distribution was observed for the on and off
      times. The abnormal distribution suggests that the quantum yields of the
      photoreactions are not constant and the molecules undergo the reactions after
      absorbing a certain number of photons. A multilocal minima model was proposed to
      explain the environmental effect.

PMID- 17432859
TI  - Amplified analysis of low-molecular-weight substrates or proteins by the self
      assembly of DNAzyme-aptamer conjugates.

PMID- 17432861
TI  - Synthesis of cyclopropanes via Pd(II/IV)-catalyzed reactions of enynes.

PMID- 17432860
TI  - Cisplatin damage overrides the predefined rotational setting of positioned
      nucleosomes.
AB  - Cisplatin and carboplatin are used successfully to treat various types of cancer.
      The drugs target the nucleosomes of cancer cells and form intrastrand DNA cross
      links that are located in the major groove. We constructed two site-specifically
      modified nucleosomes containing defined intrastrand cis-{Pt(NH3)2}(2+) 1,3
      d(GpTpG) cross-links. Histones from HeLa-S3 cancer cells were transferred onto
      synthetic DNA duplexes having nucleosome positioning sequences. The structures of
      these complexes were investigated by hydroxyl radical footprinting. Employing
      nucleosome positioning sequences allowed us to quantify the structural deviation
      induced by the cisplatin adduct. Our experiments demonstrate that a platinum
      cross-link locally overrides the rotational setting predefined in the nucleosome
      positioning sequence such that the lesion faces toward the histone core.
      Identical results were obtained for two DNA duplexes in which the sites of
      platination differed by approximately half a helical turn. Additionally, we
      determined that cisplatin unwinds nucleosomal DNA globally by approximately 24
      degree. The intrastrand cis-{Pt(NH3)2}(2+) 1,3-d(GpTpG) cross-links are located
      in an area of the nucleosome that contains locally overwound DNA in undamaged
      reference nucleosomes. Because most nucleosome positions in vivo are defined by
      the intrinsic DNA sequence, the ability of cisplatin to influence the structure
      of these positioned nucleosomes may be of physiological relevance.

PMID- 17432862
TI  - Gold(I)-catalyzed oxidative rearrangements.

PMID- 17432863
TI  - Control of the electrode-molecule interface for molecular devices.

PMID- 17432865
TI  - Dependence of DNA sequence selectivity and cell cytotoxicity on azinomycin A and
      B epoxyamide stereochemistry.
AB  - Evaluation of the importance of C18/C19 stereochemistry of azinomycin A/B
      epoxyamide partial structures with respect to DNA alkylation sequence selectivity
      is reported using a unique assay with a DNA oligomer containing imbedded normal
      (5'-GGC-3'/3'-CCG-5') and inverted (5'-CGG-3'/3'-GCC-5') azinomycin consensus
      cross-linking sequences. Both species were found to have unique selectivity
      profiles and alkylate DNA in a manner distinct from azinomycin B. Computational
      docking experiments support altered binding modes for the enantiomers.

PMID- 17432866
TI  - Synthesis of perfluoroalkylated benzenes and pyridines through cationic
      Rh(I)/modified BINAP-catalyzed chemo- and regioselective [2 + 2 + 2]
      cycloaddition.
AB  - A convenient synthesis of perfluoroalkylated benzenes and pyridines has been
      achieved by a cationic Rh(I)/modified BINAP-complex-catalyzed chemo- and
      regioselective [2 + 2 + 2] cycloaddition of alkynes with a
      perfluoroalkylacetylene and a perfluoroalkylnitrile.

PMID- 17432867
TI  - Stereoselective glycosylations of 2-azido-2-deoxy-glucosides using intermediate
      sulfonium ions.
AB  - TMSOTf-promoted glycosylations of 2-azido-2-deoxy-glucosyl trichloroacetimidates
      provide excellent alpha-anomeric selectivities when performed at a relatively
      high reaction temperature in the presence of PhSEt or thiophene. NMR and
      computation studies have shown that these glycosylations proceed through an
      equatorial anomeric sulfonium ion, which upon displacement by a sugar alcohol
      provides an axial glycoside. Computational studies have indicated that steric
      factors determine the selective formation of the beta-anomeric sulfonium ion.

PMID- 17432868
TI  - Highly efficient and mild cascade reactions triggered by
      bis(triphenyl)oxodiphosphonium trifluoromethanesulfonate and a concise total
      synthesis of camptothecin.
AB  - A mild and efficient cascade methodology is reported to construct variously
      substituted indolizino[1,2-b]quinolin-9(11H)-ones. Efficiently triggered by
      bis(triphenyl)oxodiphosphonium trifluoromethanesulfonate under mild conditions,
      this cascade achieved significant enhancements in chemical yields. Utilizing this
      highly efficient domino reaction followed by a Sharpless dihydroxylation, an
      eight-step total synthesis of camptothecin was accomplished from a known pyridine
      derivative in direct fashion with an overall yield of 47% and 95% ee.

PMID- 17432869
TI  - Preparation of whey protein hydrolysates using a single- and two-stage enzymatic
      membrane reactor and their immunological and antioxidant properties:
      characterization by multivariate data analysis.
AB  - An initial 5% (w/v), followed thereafter with replacement aliquots of 3% (w/v),
      whey protein isolate (WPI) (ca. 86.98% Kjeldahl N x 6.38), was hydrolyzed using
      Protease N Amano G (IUB 3.4.24.28, Bacillus subtilis) in an enzymatic membrane
      reactor (EMR) fitted with either a 10 or 3 kDa nominal molecular weight cutoff
      (NMWCO) tangential flow filter (TFF) membrane. The hydrolysates were desalted by
      adsorption onto a styrene-based macroporous adsorption resin (MAR) and washed
      with deionized water to remove the alkali, and the peptides were desorbed with
      25, 50, and 95% (v/v) ethyl alcohol. The desalted hydrolysates were analyzed for
      antibody binding, free radical scavenging, and molecular mass analysis as well as
      total and free amino acids (FAA). For the first time a quantity called IC50, the
      concentration of peptides causing 50% inhibition of the available antibody, is
      introduced to quantify inhibition enzyme-linked immunosorbent assay (ELISA)
      properties. Principal component analysis (PCA) was used for data reduction. The
      hydrolysate molecular mass provided the most prominent influence (PC1 = 57.35%),
      followed by inhibition ELISA (PC2 = 18.90%) and the antioxidant properties (PC3 =
      10.43%). Ash was significantly reduced in the desalted fractions; the protein
      adsorption recoveries were high, whereas desorption with alcohol was prominently
      influenced by the hydrophobic/ hydrophilic amino acid balance. After hydrolysis,
      some hydrolysates showed increased ELISA reactivity compared with the native WPI.

PMID- 17432870
TI  - Heat expanded starch-based compositions.
AB  - A heat expansion process similar to that used for expanded bead polystyrene was
      used to expand starch-based compositions. Foam beads made by solvent extraction
      had the appearance of polystyrene beads but did not expand when heated due to an
      open-cell structure. Nonporous beads, pellets, or particles were made by
      extrusion or by drying and milling cooked starch slurries. The samples expanded
      into a low-density foam by heating 190-210 degrees C for more than 20 s at
      ambient pressures. Formulations containing starch (50-85%), sorbitol (5-15%),
      glycerol (4-12%), ethylene vinyl alcohol (EVAL, 5-15%), and water (10-20%) were
      studied. The bulk density was negatively correlated to sorbitol, glycerol, and
      water content. Increasing the EVAL content increased the bulk density, especially
      at concentrations higher than 15%. Poly(vinyl alcohol) (PVAL) increased the bulk
      density more than EVAL. The bulk density was lowest in samples made of wheat and
      potato starch as compared to corn starch. The expansion temperature for the
      starch pellets decreased more than 20 degrees C as the moisture content was
      increased from 10 to 25%. The addition of EVAL in the formulations decreased the
      equilibrium moisture content of the foam and reduced the water absorption during
      a 1 h soaking period.

PMID- 17432871
TI  - Improved HPLC-MS/MS method for determination of isoxaflutole (balance) and its
      metabolites in soils and forage plants.
AB  - A robust multi-residue procedure is needed for the analysis of the pro-herbicide
      isoxaflutole and its degradates in soil and plant materials at environmentally
      relevant (<1 microg kg-1) levels. An analytical method using turbo-spray and heat
      nebulizer high-performance liquid chromatography-tandem mass spectrometry (HPLC
      MS/MS) was developed for the analysis of isoxaflutole (IXF) and its two
      metabolites, diketonitrile (DKN) and the benzoic acid metabolite (BA), at sub
      microgram per kilogram levels in soil and plant samples. The average recoveries
      of the three compounds in spiked soil and plant samples ranged from 84 to 110%
      and 94 to 105%, respectively. The limits of quantification were validated at 0.06
      microg kg-1 for soil and 0.3 microg kg-1 for plant samples. The limits of
      detection (LOD) for soil analysis were 0.01, 0.002, and 0.01 microg kg-1 for IXF,
      DKN, and BA, respectively. Corresponding LOD for the plant analysis method were
      0.05, 0.01, and 0.05 microg kg-1. The developed method was validated using forage
      grass and soil samples collected from a field lysimeter study in which IXF was
      applied to each of four forage treatments. Forage plants and soils were sampled
      for analyses 25 days after IXF application to the soil. In soils, IXF was not
      detected in any treatment, and DKN was the predominant metabolite found. In
      forage plants, the concentrations of DKN and BA were 10-100-fold higher than that
      in soil samples, but IXF was not detected in any forage plants. The much higher
      proportion of BA to DKN in plant tissues (23-53%), as compared to soils (0-5%),
      suggested that these forages were capable of detoxifying DKN. The developed
      methods provided LODs at sub-microgram per kilogram levels to determine the fate
      of IXF and its metabolites in soils and forage plants, and they also represent
      considerable improvements in extraction recovery rates and detection sensitivity
      as compared to previous analytical methods for these compounds.

PMID- 17432872
TI  - Cloning and expression of the XPR2 gene from Yarrowia lipolytica in Pichia
      pastoris.
AB  - Yarrowia lipolytica is a dimorphic yeast able to secrete different types of
      proteases depending on the pH of the environment. At neutral pH, the production
      of an extracellular alkaline protease (AEP) is induced. This protease could be
      useful in the leather, detergent, or food industries. The XPR2 gene, coding for
      AEP, was extracted from the pINA154 vector and cloned into the pHIL-D2 vector to
      obtain a new protease-producing recombinant Pichia pastoris strain. The gene was
      efficiently integrated in the P. pastoris genome and expressed from the AOX1
      promoter actively induced by methanol. Finally, the protease was successfully
      secreted by P. pastoris GS115.

PMID- 17432873
TI  - Production of xylooligosaccharides from xylans by extracellular xylanases from
      Thermobifida fusca.
AB  - Xylooligosaccharides are produced for use as a valuable food sweetener or
      additive. They have many beneficial biomedical and health effects. In this study,
      a process for producing xylooligosaccharides from lignocellulolytic agricultural
      waste was developed. Bagasse, corncob, wheat bran, and peanut shell were used as
      carbon sources for production of xylanolytic enzymes from Thermobifida fusca
      NTU22. When using bagasse as the carbon source, the xylanolytic enzymes that
      simultaneously accumulated in the broth in a 500 mL Hinton flask after 72 h of
      cultivation at 50 degrees C were measured as xylanase (14.0 U/mL), beta
      xylosidase (74.1 mU/mL), and acetyl esterase (29.1 mU/mL). The optimum pH and
      temperature for xylanases were 6.0-8.0 and 70 degrees C, respectively. Six
      proteins with xylanase activity were identified by zymogram analysis of
      isoelectric focusing gel. This was followed by heat treatment at 70 degrees C for
      30 min that eliminated 90% of the beta-xylosidase activity. The xylanase and
      acetyl esterase activities were still 100%. Two percent of xylan extracted from
      the bagasse was then hydrolyzed by heat-treated crude xylanase preparation at 60
      degrees C, pH 7.0, for 10 h. The xylooligosaccharides that accumulated in the
      broth were about 23.7%. After the purification process by activated charcoal
      chromatography, the purity of xylooligosaccharides was 71.4%.

PMID- 17432874
TI  - Fractionation of zein by size exclusion chromatography.
AB  - Zein is a group of alcohol-soluble corn proteins, which consists of several
      individual proteins. A single-step gel filtration chromatography method was
      developed to fractionate individual zeins from ethanol extracts of whole corn. A
      Superdex prep 75 column was used with different mobile phases to fractionate the
      zeins, which were analyzed by SDS-PAGE and UV spectrophotometry. With 70% aqueous
      ethanol as the mobile phase, fractions containing a mixture of alpha-zein/beta
      zein and alpha-zein/delta-zein were obtained. With ammonium bicarbonate added to
      the 70% ethanol mobile phase, it was possible to obtain beta-zein and delta-zein
      fractions devoid of other proteins. However, all fractions containing alpha-zein
      also contained minor amounts of delta-zein and/or beta-zein. Almost all fractions
      also contained non-protein impurities.

PMID- 17432875
TI  - Pressurized water extraction of polysaccharides as secondary metabolites from
      Lentinula edodes.
AB  - The suitability of pressurized water extraction (PWE) of crude polysaccharides as
      secondary metabolites from Lentinula edodes was investigated. A series of
      experiments were carried out to examine the effects of extraction times and
      pressures. The results indicated that the maximum recovery of polysaccharides was
      about 90% of the crude polysaccharides from mycelia pellets when the pressure was
      at 10.1 MPa for 70 min (28 degrees C). This was a drastic improvement over that
      of boiling water extraction (BWE) at 0.1 MPa for 40 min, which gave only 27.9%
      recovery. A nitroblue tetrazolium (NBT) reduction assay was used to examine the
      macrophage stimulating activities (MSA), and it was found that the PWE
      polysaccharides retained the MSA. The morphology of the macrophage cells treated
      by PWE polysaccharides was also examined and found to be similar to that of the
      positive control lipopolysaccharides treated. Finally, gel chromatographic and
      NMR experiments revealed that both PWE and BWE polysaccharides showed the
      presence of four similar molecular mass components and the alpha-(1-->4)-D-Glcp
      and beta-(1-->6)-D-Glcp linkage residues. The improved PWE efficiency is probably
      due to the possibility that under high pressure, the solid polysaccharide's
      hydrogen bonding is partially destroyed to increase structure elasticity and
      water solubility.

PMID- 17432876
TI  - Inhibition of photophosphorylation and electron transport chain in thylakoids by
      lasiodiplodin, a natural product from Botryosphaeria rhodina.
AB  - Four natural products were isolated from the fungus Botryosphaeria rhodina, and
      their effects on photosynthesis were tested. Only lasiodiplodin (1) inhibited ATP
      synthesis and electron flow from water to methylviologen; therefore, it acts as a
      Hill reaction inhibitor in freshly lysed spinach thylakoids. Photosystem I and II
      and partial reactions as well as ATPase were measured in the presence of 1. Three
      new different sites of 1 interaction and inhibition were found: one at CF1, the
      second in the water-splitting enzyme, and the third at the electron-transfer path
      between P680 and QA; these targets are different from that of the synthetic
      herbicides present. Electron transport chain inhibition by 1 was corroborated by
      fluorescence induction kinetics studies.

PMID- 17432877
TI  - Delipidation of a whey protein concentrate by electroacidification with bipolar
      membranes.
AB  - The separation of residual fats from whey protein concentrates (WPC) results in a
      better nutritional and functional utilization of this product. Bipolar membrane
      electroacidification (BMEA) technology allows acidification and demineralization
      of solutions without any salt addition. The principle of BMEA is based on proton
      formation from water molecule dissociation at the bipolar membrane interface. The
      objective of this work was to determine the effect of an electroacidification
      treatment at pH 4.5 on the precipitation of lipids. WPC electroacidification was
      carried out with or without preliminary demineralization by conventional
      electrodialysis. The effect of ionic strength on lipid precipitation rates was
      also evaluated by dilution of the WPC samples. Lipid precipitation levels of 35
      39% were obtained using the electroacidification process without a dilution step,
      while the combination of BMEA and dilution of the WPC resulted in a decrease in
      lipid content by six-fold from 0.76 to 0.21%.

PMID- 17432878
TI  - Role of alpha-Asp181, beta-Asp192, and gamma-Asp190 in the distinctive subunits
      of human NAD-specific isocitrate dehydrogenase.
AB  - Human NAD-dependent isocitrate dehydrogenase (IDH) is allosterically activated by
      ADP by lowering the Km for isocitrate. The enzyme has three subunit types with
      distinguishable sequences present in the approximate ratio 2alpha:1beta:1gamma
      and, per tetramer, binds 2 mol of each ligand. To evaluate whether the subunits
      also have distinct functions, we replaced equivalent aspartates, one subunit at a
      time, by asparagines; each expressed, purified enzyme was composed of one mutant
      and two wild-type subunits. The aspartates were chosen because beta-Asp192 and
      gamma-Asp190 had previously been affinity labeled by a reactive ADP analogue and
      alpha-Asp181 is equivalent based on sequence alignments. The alpha-D181N IDH
      mutant exhibits a 2000-fold decrease in Vmax, with increases of 15-fold in the
      Kms for Mn(II) and NAD and a much smaller change in the Km for isocitrate. In
      contrast, the Vmax values of the beta-D192N and gamma-D190N IDHs are only reduced
      4-5-fold as compared to wild-type enzyme. The Km for NAD of the beta-D192N enzyme
      is 9 times that of the normal enzyme with little or no effect on the affinity for
      Mn(II) or isocitrate, while the Kms for coenzyme and for Mn(II) of the gamma
      D190N enzyme are 19 and 72 times, respectively, that of the normal enzyme with a
      much smaller effect on the Km for isocitrate. Finally, all three mutant enzymes
      fail to respond to ADP by lowering the Km for isocitrate, although they do bind
      ADP. Thus, these aspartates are close to but not in the ADP site and are required
      for communication between the ADP and isocitrate sites. These results demonstrate
      that alpha-Asp181 is the only one of these aspartates essential for catalysis.
      Beta-Asp192 is a determinant of the enzyme's affinity for NAD, as is gamma
      Asp190, while gamma-Asp190 also influences the enzyme's affinity for metal ion.
      We conclude that the NAD and ADP sites are shared between alpha- and beta- and
      alpha- and gamma-subunits, and the Mn(II) site is shared between alpha- and gamma
      subunits, while the alpha-subunit is essential for catalysis. Although alpha
      Asp181, beta-Asp192, and gamma-Asp190 may have derived from a common progenitor,
      these aspartates of the three subunits have evolved distinct functions.

PMID- 17432879
TI  - Uranyl acetate as a direct inhibitor of DNA-binding proteins.
AB  - Zinc finger proteins, one of the largest families of DNA-binding proteins in
      higher eukaryotes, are so named because they require zinc ions for appropriate
      structure and function. Dysregulation of zinc finger-containing DNA transcription
      and repair proteins has been proposed as a potential mechanism for the toxic
      effects of some metal ions. Uranium metal has been reported to be both a
      cytotoxic and a genotoxic agent. We hypothesized that these toxic effects of
      uranium might be due to its ability to directly disrupt zinc finger activity. To
      test this hypothesis, two purified zinc finger proteins, Aart and Sp1, were
      analyzed by electrophoretic mobility shift in the presence of uranyl acetate.
      Inhibition of binding was apparent at 10 microM uranyl acetate, while no
      inhibition was observed with up to 2000 microM the cytotoxic metalloid sodium
      arsenite. Preincubation of the DNA with uranyl acetate did not inhibit zinc
      finger protein binding, suggesting that the inhibition was due to direct uranyl
      interaction with the protein. Surprisingly, uranyl acetate inhibited two nonzinc
      finger DNA-binding proteins, AP1 and NF-kappaB, to a similar extent, and zinc
      finger inhibition was reduced in the presence of bovine serum albumin. These
      results suggest that uranium can directly inhibit the function of DNA-binding
      proteins, most likely via a nonspecific protein interaction.

PMID- 17432880
TI  - Particulate depleted uranium is cytotoxic and clastogenic to human lung cells.
AB  - Depleted uranium (DU) is commonly used in military armor and munitions, and thus,
      exposure of soldiers and non-combatants is potentially frequent and widespread.
      DU is considered a suspected human carcinogen, affecting the bronchial cells of
      the lung. However, few investigations have studied DU in human bronchial cells.
      Accordingly, we determined the cytotoxicity and clastogenicity of both
      particulate (water-insoluble) and soluble DU in human bronchial fibroblasts
      (WTHBF-6 cells). We used uranium trioxide (UO3) and uranyl acetate (UA) as
      prototypical particulate and soluble DU salts, respectively. After a 24 h
      exposure, both UO3 and UA induced concentration-dependent cytotoxicity in WTHBF-6
      cells. Specifically, 0.1, 0.5, 1, and 5 microg/cm2 UO3 induced 99, 57, 32, and 1%
      relative survival, respectively. Similarly, 100, 200, 400, and 800 microM UA
      induced 98, 92, 70, and 56% relative survival, respectively. When treated with
      chronic exposure, up to 72 h, of either UO3 or UA, there was an increased degree
      of cytotoxicity. We assessed the clastogenicity of these compounds and found that
      at concentrations of 0, 0.5, 1, and 5 microg/cm2 UO3, 5, 6, 10, and 15% of
      metaphase cells exhibit some form of chromosome damage. UA did not induce
      chromosome damage above background levels. There were slight increases in
      chromosome damage induced when we extended the UO3 treatment time to 48 or 72 h,
      but no meaningful increase in chromosome damage was observed with chronic
      exposure to UA.

PMID- 17432881
TI  - Oxidation kinetics of hydrogenated amorphous carbon (a-CH(x)) overcoats for
      magnetic data storage media.
AB  - The oxidation kinetics of a-CHx overcoats during exposure to oxygen and water
      vapor have been measured using X-ray photoemission spectroscopy (XPS) in an
      apparatus that allows oxidation and analysis of freshly deposited a-CHx overcoats
      without prior exposure of the overcoats to air. The uptake of oxygen on the
      surfaces of the a-CHx overcoats has been measured at O2 and H2O pressures in the
      range 10(-7)-10(-3) Torr at room temperature. The uptake of oxygen during O2
      exposures on the order of 10(7) Langmuirs leads to saturation of the a-CHx
      overcoat surfaces at oxidation levels on the order of 20%. This indicates that
      the surfaces of a-CHx overcoats are relatively inert to oxidation in the sense
      that the dissociative sticking coefficient of O2 is approximately 10(-6). Oxygen
      uptake during exposure to H2O vapor is similar to the uptake during exposure to
      O2 gas. Although the surfaces of the a-CHx overcoats are quite inhomogeneous, it
      has been possible to model the uptake of oxygen on their surfaces using a fairly
      simple Langmuir-Hinshelwood mechanism. Interestingly, the saturation coverage of
      oxygen during exposure to air at atmospheric pressure is approximately 6%,
      significantly lower than that obtained during low-pressure exposure to O2 gas or
      H2O vapor.

PMID- 17432882
TI  - Protein-resistant self-assembled monolayers on gold with latent aldehyde
      functions.
AB  - In the present study, oligo(ethylene glycol) (OEG)-linked alkanethiols were
      synthesized which carry a vicinal diol on one end of the OEG chain. After self
      assembled monolayer (SAM) formation on gold, the vicinal diols were converted
      into aldehyde functions by exposure to aqueous NaIO4, as previously used for SAMs
      with OEG chains buried in the center of the SAM [Jang et al. Nano Lett. 2003, 3,
      691-694]. Mixed SAMs with latent aldehydes on 5% of the OEG termini showed high
      protein resistance, which greatly slowed the kinetics of protein coupling on the
      time scale of minutes. Small bioligands (such as biocytin hydrazide) or small
      heterobifunctional crosslinkers (maleimidopropionyl hydrazide,
      pyridyldithiopropionyl hydrazide) with hydrazide functions were efficiently bound
      to the aldehyde functions on the SAM, providing for specific capture of
      streptavidin or for fast covalent binding of proteins with free thiols or
      maleimide functions, respectively. In conclusion, OEG-terminated SAMs with latent
      aldehydes serve as protein-resistant sensor surfaces which are easily
      functionalized with small ligands or with heterobifunctional crosslinkers to
      which the bait molecule is attached in a subsequent step.

PMID- 17432883
TI  - Modulation of electroosmotic flow by neutral polymers.
AB  - Polymer coating is widely used to modulate the fluid flow in micro- and nanometer
      pores and flows that are sensitive to surface properties such as electroosmotic
      flow. Here we report on the dissipative particle dynamics simulations of the
      modulation of electroosmotic flow by neutral polymers. In these coarse-grained
      simulations, fluid and polymers are resolved at a scale comparable to polymer
      size and the two-way coupling between polymer conformation and fluid flow are
      explicitly accounted for. The simulations indicate that, in the parameter space
      explored, the screening of electroosmotic flow by polymers decreases nonlinearly
      as the external electric field increases. Such an observation is understood by
      analyzing the surface coverage by polymers, height and orientation of the grafted
      polymers, and the two different modes of flow screening by polymer segments as a
      function of the external electric field. Understanding the effects and interplay
      of these physical processes is crucial for the rational design of polymer coating
      for flow control in microfluidic and nanofluidic systems.

PMID- 17432884
TI  - Growth of Cu nanobelt and Ag belt-like materials by surfactant-assisted galvanic
      reductions.
AB  - We demonstrate the syntheses of single crystalline Cu nanobelt and Ag belt-like
      materials via CTAC-assisted (CTAC, cetyltrimethylammonium chloride) galvanic
      reductions. The single crystalline face-centered cubic phase Cu nanobelt was
      prepared by reacting CuCl2(aq) with Al(s) in an aqueous solution of CTAC and
      HNO3. The Cu nanobelt exhibited a high-quality ribbon-like nanostructure with a
      thickness less than 15 nm, a width of 30-150 nm, and a length up to 10 microm.
      The belt-like Ag, with a thickness less than 10 nm, a width of 30-100 nm, a
      length up to 5 microm, and a novel single crystalline 4H structure, was prepared
      by reacting AgNO3(aq) and Cu(s) in an aqueous solution of CTAC.

PMID- 17432885
TI  - Deformations of lipid vesicles induced by attached spherical particles.
AB  - Wrapping of a spherical colloidal particle, located inside and outside a lipid
      vesicle, by the membrane which forms the wall of the vesicle is investigated. The
      process is studied for vesicles of different geometries: prolate, oblate,
      stomatocytes. We focus on the bending energy change and shape transformations
      induced by binding the membrane to the spherical particles. The ground-state
      shapes of vesicles are calculated within the framework of a Helfrich curvature
      energy functional.

PMID- 17432886
TI  - Stereospecific morphogenesis of aspartic acid helical crystals through molecular
      recognition.
AB  - Helical morphologies were generated from aspartic acid (Asp) crystals in agar gel
      matrix. The morphogenesis stereospecifically proceeded in the helical crystal
      growth: D- and L-Asp provided left- and right-handed structures, respectively.
      The backbone of the helical morphology was twisted twins of tilted unit crystals,
      as was the case with inorganic helical crystals. The molecular recognition
      between the Asp crystals and agar matrix molecules resulted in the stereospecific
      morphogenesis. The chirality in Asp and agar molecules, the enantiomorph of unit
      crystals, and the resultant macroscopic helix were exquisitely associated with
      each other.

PMID- 17432887
TI  - Highly efficient non-biofouling coating of zwitterionic polymers: poly((3
      (methacryloylamino)propyl)-dimethyl(3-sulfopropyl)ammonium hydroxide).
AB  - This work describes the formation of highly efficient non-biofouling polymeric
      thin films of poly((3-(methacryloylamino)propyl)-dimethyl(3-sulfopropyl)ammonium
      hydroxide), (poly(MPDSAH)). The poly(MPDSAH) films were generated from the self
      assembled monolayers terminating in an initiator of atom transfer radical
      polymerization (ATRP) by the surface-initiated ATRP of MPDSAH. The poly(MPDSAH)
      films on a gold surface were characterized by ellipsometry, FT-IR spectroscopy,
      contact angle goniometery, and X-ray photoelectron spectroscopy. The copper
      complexes and unpolymerized monomers trapped inside the polymer brushes were
      completely washed out by soaking the poly(MPDSAH)-coated substrate in water at 40
      degrees C for 4 days. The amount of proteins nonspecifically adsorbed onto the
      poly(MPDSAH) films was evaluated by surface plasmon resonance spectroscopy: the
      adsorption of proteins was <0.6 ng/cm(2) on the surfaces for all the model
      proteins. The ability of the poly(MPDSAH) films to resist the nonspecific
      adsorption of proteins was comparable to that of the best known systems.

PMID- 17432888
TI  - Chain polymerization of diacetylene compound multilayer films on the topmost
      surface initiated by a scanning tunneling microscope tip.
AB  - Chain polymerizations of diacetylene compound multilayer films on graphite
      substrates were examined with a scanning tunneling microscope (STM) at the
      liquid/solid interface of the phenyloctane solution. The first layer grew very
      quickly into many small domains. This was followed by the slow formation of the
      piled up layers into much larger domains. Chain polymerization on the topmost
      surface layer could be initiated by applying a pulsed voltage between the STM tip
      and the substrate, usually producing a long polymer of submicrometer length. In
      contrast, polymerizations on the underlying layer were never observed. This can
      be explained by a conformation model in which the polymer backbone is lifted up.

PMID- 17432889
TI  - Direct immobilization of cholesteryl-TEG-modified oligonucleotides onto
      hydrophobic SU-8 surfaces.
AB  - We introduce a rapid, simple one-step procedure for the high-yield immobilization
      of cholesteryl-tetraethyleneglycol-modified oligonucleotides (chol-DNA) at
      hydrophobic sites made of SU-8 photoresist. Topographic structures of SU-8 were
      microfabricated on microscope glass coverslips sputtered with a Ti/Au layer. Upon
      application, chol-DNA adsorbed to the SU-8 structures from solution, leaving the
      surrounding gold surface free of chol-DNA. chol-DNA immobilization is complete
      within 15 min and yields a surface coverage in the range of 20-95 pmol/cm(2),
      which corresponds to a film density of 10(12)-10(13) molecules/cm(2). chol-DNA
      immobilization is stable and can be sustained despite rinsing, drying, dry
      storage for several hours, and rehydration of chips. Furthermore, complementary
      DNA in solution hybridizes efficiently to immobilized chol-DNA.

PMID- 17432890
TI  - Membrane proteomic analysis of Arabidopsis thaliana using alternative
      solubilization techniques.
AB  - This study presents a comparative proteomic analysis of the membrane subproteome
      of whole Arabidopsis seedlings using 2% Brij-58 or 60% methanol to enrich and
      solubilize membrane proteins for strong cation exchange fractionation and
      reversed-phase liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total
      of 441 proteins were identified by our Brij-58 method, and 300 proteins were
      detected by our methanol-based solubilization approach. Although the total number
      of proteins obtained using the nonionic detergent was higher than the total
      obtained by organic solvent, the ratio of predicted membrane proteins to total
      proteins identified indicates up to an 18.6% greater enrichment efficiency using
      methanol. Using two different bioinformatics approaches, between 31.0 and 40.0%
      of the total proteins identified by the methanol-based method were classified as
      containing at least one putative transmembrane domain as compared to 22.0-23.4%
      for Brij-58. In terms of protein hydrophobicity as determined by the GRAVY index,
      it was revealed that methanol was more effective than Brij-58 for solubilizing
      membrane proteins ranging from -0.4 (hydrophilic) to +0.4 (hydrophobic). Methanol
      was also approximately 3-fold more effective than Brij-58 in identifying leucine
      rich repeat receptor-like kinases. The ability of methanol to effectively
      solubilize and denature both hydrophobic and hydrophilic proteins was
      demonstrated using bacteriorhodopsin and cytochrome c, respectively, where both
      proteins were identified with at least 82% sequence coverage from a single
      reversed-phase LC-MS/MS analysis. Overall, our data show that methanol is a
      better alternative for identifying a wider range of membrane proteins than the
      nonionic detergent Brij-58.

PMID- 17432891
TI  - Diversity of cAMP-dependent protein kinase isoforms and their anchoring proteins
      in mouse ventricular tissue.
AB  - Using a chemical proteomics approach, we efficiently enriched for the generally
      low abundant cAMP signaling proteins, and their interactors, directly from mouse
      ventricular tissue. The presence of undesired contaminating (noncyclic)
      nucleotide-binding proteins was diminished using a tailored sequential elution
      protocol. Through further optimization of this affinity purification and elution
      protocol, we were able to detect all known protein kinase A regulatory isoforms
      (PKA-R). Furthermore, 11 different A-kinase anchoring proteins (AKAPs) were
      detected. A proposed fusion protein of paralemmin 2 and AKAP2 could be decisively
      established as a novel AKAP at the protein level in ventricular tissue. When
      comparing this dataset of cAMP-affinity purified proteins with earlier data
      obtained with immobilized cGMP from rat ventricular tissue, we observe a large
      overlap in the retained proteins but also some clear differences. Furthermore,
      implementation of an in-depth analysis of in vivo phosphorylation sites on PKA-R
      revealed the presence of several differentially phosphorylated PKA-R isoforms.
      This illustrates yet another layer of functional regulation in cyclic nucleotide
      signaling. In general, our improved chemical proteomics screen offers a broad,
      but detailed, view on nature's complex diversity in cyclic nucleotide signaling
      mechanisms. Possibly different AKAP-isoforms may direct differentially
      phosphorylated PKA-R isoforms to different cellular compartments, providing a
      multifaceted platform for just this kinase.

PMID- 17432892
TI  - Proteomic analysis reveals a metabolism shift in a laboratory fluconazole
      resistant Candida albicans strain.
AB  - Multifactorial and multistep alterations are involved in acquired fluconazole
      (FLC) resistance in Candida albicans. In this study, a FLC-resistant C. albicans
      strain was obtained by serial cultures of a FLC-susceptible C. albicans strain in
      incrementally increasing concentrations of FLC. The comparative proteomic study,
      confirmed by real-time RT-PCR, was performed with the susceptible parental strain
      and the resistant daughter strain to identify proteins altered during the
      development of FLC resistance. Our analysis of the differentially expressed
      proteins identified 22 different proteins, most of which were related to energy
      metabolisms (e.g., Pgk1, Fba1, and Adh1), and some of which have been previously
      identified as being involved in FLC resistance in C. albicans (e.g., Ald5, Cdc19,
      and Gap1). Functional analysis revealed lower intracellular ATP level and
      mitochondrial membrane potential, less endogenous reactive oxygen species
      generation in response to antifungal agents, and identical susceptibility to
      exogenous hydrogen peroxide, heat, and hyperosmotic shock in the resistant strain
      compared with the susceptible strain. Our results suggest that a metabolism shift
      might contribute to FLC resistance in C. albicans.

PMID- 17432894
TI  - Thermoresponsive triblock copolymer aggregates investigated by laser light
      scattering.
AB  - Narrowly distributed polystyrene-b-poly(N-isopropylacrylamide)-b-polystyrene (PS
      b-PNIPAM-b-PS) triblock copolymer with trithiocarbonate group in the middle of
      PNIPAM block was synthesized by using reversible addition fragmentation chain
      transfer (RAFT) polymerization. Such copolymer chains form a micelle-like
      aggregate with PNIPAM interlocking rings and associating PS blocks as the core
      and PNIPAM rings as the corona. The hydrolysis of the trithiocarbonate group
      leads the rings in the corona to be cut into open linear coils. Using laser light
      scattering, we have investigated the temperature-induced collapse of the
      aggregates with the rings and coils in the corona. Our results reveal that the
      former shrink much less than the latter due to the topological effect of PNIPAM
      blocks in the corona. On the other hand, the aggregates with long coils exhibit a
      sharper collapse transition than those with shorter coils.

PMID- 17432893
TI  - Alterations in the serum glycome due to metastatic prostate cancer.
AB  - Glycomic profiles derived from human blood sera of 10 healthy males were compared
      to those from 24 prostate cancer patients. The profiles were acquired using MALDI
      MS of permethylated N-glycans released from 10-microL sample aliquots.
      Quantitative permethylation was attained using solid-phase permethylation.
      Principal component analysis of the glycomic profiles revealed significant
      differences among the two sets, allowing their distinct clustering. The first
      principal component distinguished the 24 prostate cancer patients from the
      healthy individuals. It was determined that fucosylation of glycan structures is
      generally higher in cancer samples (ANOVA test p-value of 0.0006). Although more
      than 50 N-glycan structures were determined, 12 glycan structures, of which six
      were fucosylated, were significantly different between the two sample sets.
      Significant differences were confirmed through two independent statistical tests
      (ANOVA and ROC analyses). Ten of these structures had significantly higher
      relative intensities in the case of the cancer samples, while the other two were
      less abundant in the cancer samples. All 12 structures were statistically
      significant, as suggested by their very low ANOVA scores (<0.001) and ROC
      analysis, with area under the curve values close to 1 or 0. Accordingly, these
      structures can be considered as cancer-specific glycans and potential prostate
      cancer biomarkers. Therefore, serum glycomic profiling appears worthy of further
      investigation to define its role in cancer early detection and prognostication.

PMID- 17432895
TI  - Symmetry selection in artificial DNA base pairs.
AB  - We report the results of density functional theory (DFT) studies on the formation
      of the complex H1--Cu2+-H1- consisting of two deprotonated hydroxypyridone
      ligands (H1-) and a Cu2+ ion. We compare the total energies of three possible
      structures with different symmetries and show that the structure with plane
      reflection symmetry has the lowest energy. The electronic structure of the
      periodic extended DNA-like double helix consisting of stacked H1--Cu2+-H1- units
      is then calculated within the density functional method, and the double helix is
      found to be an insulating ferromagnet.

PMID- 17432896
TI  - Influence of the substituted side group on the molecular structure and electronic
      properties of TPP and related implications on organic zeolites use.
AB  - Tris(o-phenylenedioxy)cyclotriphosphazene (TPP) became a compound of choice to
      investigate the structural features of organic zeolite and their potential
      applications. Different TPP-like materials are studied in this Letter from the
      electron-donor (E-D) capacity viewpoint, since this was reported as a stabilizing
      parameter of the TPP-Lewis acid inclusion compound up to high temperatures. On
      the basis of DFT-PBE0/6-31G(d,p) calculations, the results reported herein show a
      tight dependence of the E-D of the entire molecule on that of the side group. It
      was shown that both the O/NH substitution and the extension of the
      phenylenedioxyl group with an aromatic ring significantly enhance the E-D. As a
      result, the corresponding clathrates, including some reported ones, may also be
      exploited for the same issue, with an even wider range of operating temperatures
      when trapping compounds of Lewis acidity character comparable to that of I2.
      Furthermore, it was concluded that these two strategies may significantly enhance
      the E-D capacity without altering the tolerance of TPP-like host materials to the
      guest molecules.

PMID- 17432897
TI  - Hofmeister salt effects on surface tension arise from partitioning of anions and
      cations between bulk water and the air-water interface.
AB  - We apply a recently developed surface-bulk partitioning model to interpret the
      effects of individual Hofmeister cations and anions on the surface tension of
      water. The most surface-excluded salt (Na2SO4) provides a minimum estimate for
      the number of water molecules per unit area of the surface region of 0.2 H2O A-2.
      This corresponds to a lower bound thickness of the surface region of
      approximately 6 A, which we assume is a property of this region and not of the
      salt investigated. At salt concentrations < or = 1 m, single-ion partition
      coefficients Kp,i, defined relative to Kp,Na+ = Kp,SO42- = 0, are found to be
      independent of bulk salt concentration and additive for different salt ions.
      Semiquantitative agreement with surface-sensitive spectroscopy data and molecular
      dynamics simulations is attained. In most cases, the rank orders of Kp,i for both
      anions and cations follow the conventional Hofmeister series, qualitative
      rankings of ions based on their effects on protein processes (folding,
      precipitation, assembly). Most anions that favor processes that expose protein
      surface to water (e.g., SCN-), and hence must interact favorably with (i.e.,
      accumulate at) protein surface, are also accumulated at the air-water interface
      (Kp >1, e.g., Kp,SCN- =1.6). Most anions that favor processes that remove protein
      surface from water (e.g., F-), and hence are excluded from protein surface, are
      also excluded from the air-water interface (Kp,F- = 0.5). The guanidinium cation,
      a strong protein denaturant and therefore accumulated at the protein surface
      exposed in unfolding, is somewhat excluded from the air-water surface (Kp,GuH+ =
      0.7), but is much less excluded than alkali metal cations (e.g., Kp,Na+ identical
      with 0, Kp,K+ = 0.1). Hence, cation Kp values for the air-water surface appear
      shifted (toward exclusion) as compared with values inferred for interactions of
      these cations with protein surface.

PMID- 17432898
TI  - Visualization of different pathways of DNA release from interpolyelectrolyte
      complex.
AB  - The release of double-stranded DNA from its interpolyelectrolyte complex with
      positively charged poly(allylamine hydrochloride) via exchange reaction with
      added polyanion, poly(sodium styrenesulfonate), is directly observed by
      fluorescence microscopy. It is shown that the pathways of DNA release depend
      essentially on the amount of added low-molecular-weight salt. At low salt
      content, the DNA release proceeds via the formation of an intermediate "beads-on
      string" structure, whereas at high salt content the release goes directly from
      globule to coil states without any intermediate structures. The reasons for
      different character of DNA release are discussed.

PMID- 17432899
TI  - Interaction of guanine, its anions, and radicals with lysine in different charge
      states.
AB  - Modification in DNA or protein structure can severely affect DNA-protein
      interactions and the functioning of biological systems. Some new insights into
      radiation-induced effects of guanine-lysine interactions have been obtained here
      by theoretical investigations. Geometries of zwitterionic and non-zwitterionic
      lysine in different charge states (neutral, radical cation, and protonated
      cation) were optimized employing the B3LYP/6-31G** and B3LYP/AUG-cc-pVDZ levels
      of hybrid density functional theory (DFT) and using the second-order Moller
      Plesset perturbation theory along with the 6-31G** basis set. In the case of
      neutral lysine in the gas phase, no zwitterionic structure was obtained. The non
      zwitterionic structures of lysine in radical and protonated cationic forms are
      appreciably more stable than the corresponding zwitterionic structures in the gas
      phase as obtained at all levels of theory employed here. Binding of guanine and
      different dehydrogenated guanine radicals with lysine in different charge states
      was studied at the B3LYP/6-31G** level of DFT. When guanine makes a complex with
      the lysine radical cation, large amounts of spin and positive charge densities
      are transferred from the lysine radical cation to guanine and the guanine is thus
      converted from its normal form to the radical cationic form. Complexation of the
      lysine radical cation with the H1-hydrogen-abstracted guanine radical leads to
      CO2 liberation and proton transfer from lysine. These results are compared with
      the available experimental ones.

PMID- 17432900
TI  - Structural and pathway complexity of beta-strand reorganization within aggregates
      of human transthyretin(105-115) peptide.
AB  - Interstrand conformational rearrangements of human transthyretin peptide (TTR(105
      115)) within dimeric aggregates were simulated by means of molecular dynamics
      (MD) with implicit solvation model for a total length of 48 micros. The
      conformations sampled in the MD simulations were clustered to identify free
      energy minima without any projections of free energy surface. A connected graph
      was constructed with nodes (=clusters) and edges corresponding to free energy
      minima and transitions between nodes, respectively. This connected graph which
      reflects the complexity of the free energy surface was used to extract the
      transition disconnectivity graph, which reflects the overall free energy barriers
      between pairs of free energy minima but does not contain information on
      transition paths. The routes of transitions between important free energy minima
      were obtained by further processing the original graph and the MD data. We have
      found that both parallel and antiparallel aggregates are populated. The parallel
      aggregates with different alignment patterns are separated by nonnegligible free
      energy barriers. Multiroutes exist in the interstrand conformational
      reorganization. Most visited routes do not dominant the kinetics, while less
      visited routes contribute a little each but they are numerous and their total
      contributions are actually dominant. There are various kinds of reptation
      motions, including those through a beta-bulge, side-chain aided reptation, and
      flipping or rotation of a hairpin formed by one strand.

PMID- 17432901
TI  - Novel preparation method for poly(L-lactide)-based block copolymers: extended
      chain crystallites as a solid-state macro-coinitiator.
AB  - A novel synthetic method for poly(L-lactide) (PLLA)-based diblock copolymers was
      developed by the use of PLLA extended chain crystallites (or crystalline
      residues) as a solid-state macro-coinitiator. In this study, we showed one
      example, i.e., a synthesis of diblock copolymer composed of a crystalline PLLA
      chain and an amorphous poly(DL-lactide) chain by ring-opening polymerization of
      DL-lactide initiated with stannous octoate (i.e., tin(II) 2-ethylhexanoate) in
      the presence of PLLA extended chain crystallites. The PLLA extended chain
      crystallites were prepared by hydrolytic degradation of crystallized PLLA films
      at 97 degrees C for 70 h. The chains inside the extended chain crystallites are
      expected to be protected from transesterfication reaction. Gel permeation
      chromatography, polarimetry, 1H NMR spectroscopy, wide-angle X-ray scattering,
      and differential scanning calorimetry revealed that the diblock copolymer poly(L
      lactide-block-DL-lactide) was successfully prepared without significant
      transesterification.

PMID- 17432902
TI  - Structures of pahayokolides A and B, cyclic peptides from a Lyngbya sp.
AB  - The isolation and structure elucidation of two cyclic peptides, pahayokolides A
      (1) and B (2), is described. Structural features determined for these compounds
      include a pendent N-acetyl-N-methyl leucine, both E- and Z-dehydrobutyrines, a
      homophenylalanine, and an unusual polyhydroxy amino acid that is most likely of
      mixed polyketide synthase/nonribosomal peptide synthase origin. These peptides
      were purified from a new species of cyanobacteria of the genus Lyngbya, which was
      isolated from a periphyton mat from the Florida Everglades.

PMID- 17432903
TI  - C19-diterpenoid alkaloids from Aconitum hemsleyanum var. circinatum.
AB  - Seven new C19-diterpenoid alkaloids, circinasines A-G (1-7), together with six
      known compounds, talatisamine, yunaconitine, senbusine A, sachaconitine,
      hemsleyanisine, and isohemsleyanisine, were isolated from the roots of Aconitum
      hemsleyanum var. circinatum. The structures of 1-7 were determined by the
      interpretation of spectroscopic data and by the single-crystal X-ray
      crystallographic analysis of 6 and the acetonide derivative of 1. In addition,
      the structures of hemsleyanisine and isohemsleyanisine were revised from 8 and 9
      to 10 and 11, respectively.

PMID- 17432904
TI  - Cytotoxic germacranolides and acyclic diterpenoides from the seeds of Carpesium
      triste.
AB  - Four new highly oxygenated germacranolides (1, 4, 6, and 7) and four new acyclic
      diterpenes (8-11), along with three known germacranolides (2, 3, and 5), were
      isolated from the seeds of Carpesium triste. The structures of the new compounds
      were elucidated by spectroscopic methods including IR, HRESIMS, and 1D and 2D NMR
      experiments, and the absolute configurations of compounds 1 and 8-10 were
      established by CD and Mosher's methods, respectively. Compounds 1, 2, and 4-10
      were evaluated for their in vitro cytotoxic activity against cultured SMMC-7721
      (human hepatoma), HL-60 (human promyelocytic leukemia), and L02 (human
      hepatocyte) cell lines. Compounds 1, 2, and 4-7 exhibited significant
      cytotoxicity against HL-60 cells, and compound 10 exhibited cytotoxicity against
      SMMC-7721 cells.

PMID- 17432905
TI  - Synthesis of biologically active peptide nucleic acid-peptide conjugates by
      sortase-mediated ligation.
AB  - Sortase A is a transpeptidase that cleaves at a pentapeptide-motif and
      subsequently transfers the acyl component to a nucleophile containing N-terminal
      oligoglycines. We investigate the reaction conditions of the sortase-mediated
      ligation and demonstrate a useful application by the synthesis of a peptide
      nucleic acid-cell-penetrating peptide chimera, the reaction equilibrium of which
      can be shifted in favor of the product by dialyzing out the low molecular weight
      byproduct. The synthesized conjugate exhibits dose-dependent antisense activity.

PMID- 17432906
TI  - Direct and facile syntheses of heterocyclic vinyl-C-nucleosides for recognition
      of inverted base pairs by DNA triple helix formation: first report by direct
      Wittig route.
AB  - The ability to recognize specific gene sequences canonically would allow precise
      means for genetic intervention. However, specific recognition of two of the four
      possible base pairs by triplex-forming oligonucleotides (TFO) as X.T-A and Y.C-G
      within a triplex currently remains elusive. A series of C1-vinyl nucleosides have
      been proposed, and their stability and specificity have been evaluated
      extensively by molecular dynamics simulation. Because most C-nucleoside syntheses
      extend through direct substitution at the C1-position, a more convenient strategy
      for their syntheses via a direct Wittig coupling is presented here.

PMID- 17432907
TI  - Synthesis of Z-5-carboxymethylene-1,3-dioxolan-4-ones: a better way.
AB  - The title compounds were prepared by a straightforward two-step procedure.
      Tartaric acid was first protected as either a bis(ketal) or a bis(acetal). This
      intermediate was then treated with potassium tert-butoxide at reduced temperature
      to effect a stereoselective elimination leading to the Z diastereomer of the
      alpha,beta-unsaturated acid. This protocol is useful for the laboratory-scale
      synthesis of these compounds but can also be scaled up to produce kilogram
      quantities of the material.

PMID- 17432908
TI  - Studies on the thermal ring-opening reactions of cis-3,4
      bis(organosilyl)cyclobutenes.
AB  - Three cis-3,4-bis(organosilyl)cyclobutenes were synthesized, and their thermal
      ring-opening reactions were studied. The ring-opening reaction of cis-3,4
      bis(trimethylsilyl)cyclobutene proceeded remarkably faster than that of cis-3,4
      dimethylcyclobutene. The significant rate acceleration was explained by assuming
      (i) stabilization of the transition state by electron delocalization from the
      cyclobutene HOMO to the Si-CH3 sigma* orbital, (ii) destabilization of the ground
      state by intramolecular interaction between the C-Si sigma orbitals and the pi
      orbital of cyclobutene, and (iii) through-space steric repulsion of the two bulky
      trimethylsilyl groups in a cis arrangement. The ring-opening reaction of
      unsymmetrical cis-3,4-bis(arylsilyl)cyclobutenes having electronically different
      arylsilyl groups was also examined. The inward preference increased in the order,
      p-CH3OC6H4-Si, C6H5-Si, p-CF3C6H4-Si, supporting the interpretation of the origin
      of the inward preference of silyl substituents on the basis of a stabilizing
      interaction between the cyclobutene HOMO and the Si-C sigma* orbital at the
      transition state.

PMID- 17432909
TI  - Intramolecular general acid catalysis of the hydrolysis of 2-(2'
      imidazolium)phenyl phosphate, and bond length-reactivity correlations for
      reactions of phosphate monoester monoanions.
AB  - Rate constants for the hydrolysis of 2-(2'-imidazolium)phenyl hydrogen phosphate
      (IMPP) in water at pH<6 indicate that activation by the imidazolium moiety
      disappears with the deprotonation of the phosphate group, and the reaction
      involves the hydrogen-bonding of the imidazolium NH with the aryl oxygen leaving
      group. The reaction should involve a near-planar conformation of the imidazolium
      and the phenyl groups in the activated complex, which favors proton-transfer. The
      crystal structure of IMPP was solved, and a bond length-reactivity correlation
      for reactions of phosphate monoester monoanions is described.

PMID- 17432910
TI  - Regiocontrol of the palladium-catalyzed tin hydride addition to Z-enynols:
      remarkable Z-directing effects.
AB  - Palladium-catalyzed hydrostannation of substituted Z- and E-enynols is discussed
      and compared. The regioselectivity of the H-Sn bond addition was found to be
      controlled by the geometry of the double bond (Z- or syn-directing effect) rather
      than the nature of its substituents. Exclusively alpha-vinyl stannanes were
      obtained from Z-enynols having various substituents on the double bond regardless
      of their electronic, steric, or chelating natures.

PMID- 17432911
TI  - New dimeric compounds of avenanthramide phytoalexin in oats.
AB  - Avenanthramide B is an oat phytoalexin produced in response to pathogen attack
      and elicitation. We found the formation of new dimers (1-5) of avenanthramide B
      in elicited oat leaves. The dimers were synthesized by a reaction of peroxidase
      and avenanthramide B in the presence of hydrogen peroxide. The structures of 1-5
      were determined by spectroscopic analyses, chemical derivatization, and 15N
      labeling. Compound 1 was a dehydrodimer of avenanthramide B with a bisbutane
      lactam skeleton, while 2-4 were monohydrated dehydrodimers with butane lactam
      structures. Compound 5 was also a monohydrated dehydrodimer but with a
      tetrahydrofuran structure. All the compounds were classified into lignanamides
      that were formed by an 8'-8' coupling reaction between two avenanthramide B
      units.

PMID- 17432912
TI  - Triptycene-based expanded oxacalixarenes: synthesis, structure, and tubular
      assemblies in the solid state.
AB  - Owing to the unique 3D rigid structure of triptycene, two novel expanded
      oxacalixarenes 5a and 5b as a pair of diastereomers were efficiently synthesized
      in a single step by the SNAr reaction of 2,7-dihydroxytriptycene with 2,3,5,6
      tetrachloropyridine in the presence of cesium carbonate. Similarly, two pairs of
      other triptycene-based expanded oxaxalixaenes 7a,7b and 9a,9b could also be
      obtained by the SNAr reactions of 2,7-dihydroxytriptycene with 1,5-difluoro-2,4
      dinitrobenzene and cyanuric chloride, respectively. The structures of the
      expanded oxacalixarenes were studied by NMR, MS spectra, and X-ray crystal
      structure analyses. It was found that the expanded oxacalixarene 9b showed a
      dynamic interconversion between boat and chair conformations. Moreover, we also
      found that the expanded oxacalixarenes 5a, 5b, and 9a could all assemble into
      organic tubular structures and further porous architectures in the solid state,
      in which chlorine bonding, such as C-Cl...Cl, C-Cl...O, and C-Cl...pi
      interactions, played an important role.

PMID- 17432913
TI  - Selective sensing of citrate by a supramolecular 1,8-naphthalimide/calix[4]arene
      assembly via complexation-modulated pKa shifts in a ternary complex.
AB  - A water-soluble supramolecular sensing assembly, composed of an imidazolium
      substituted calix[4]arene and a fluorescent aminodiacetate derivative of 1,8
      naphthalimide, was studied. Addition of citrate led to a large fluorescence
      enhancement, while tartrate, acetate, as well as selected inorganic anions gave
      smaller effects. The sensing principle and selectivity for citrate rely on the
      formation of a ternary fluorophore-host-anion complex and complexation-induced
      pKa shifts of an amino group attached to the fluorophore. The complexation of
      citrate induces a protonation of the amino group, which switches off
      intramolecular photoinduced electron transfer as the fluorescence quenching
      pathway, leading to an enhancement of the optical output signal. The intricate
      sensor principle was corroborated by pH titrations, binding constants, and
      structural information as obtained by 1H NMR spectroscopy.

PMID- 17432914
TI  - Asymmetric route to pyridines bearing a highly functionalized 2-alkyl substituent
      by aziridine ring-opening reactions.
AB  - The aziridine prepared from the 2-pyridineimine derived from (S)-valinol
      underwent ring-opening by attack of nitrogen, sulfur, and oxygen nucleophiles.
      Complete or prevalent regioselectivity was obtained using cerium trichloride
      heptahydrate as a catalyst. In some cases, the N-substituent could be removed by
      an oxidative protocol.

PMID- 17432915
TI  - Microwave-assisted Piloty-Robinson synthesis of 3,4-disubstituted pyrroles.
AB  - The synthesis of N-acyl 3,4-disubstituted pyrroles can be accomplished directly
      from hydrazine and an aldehyde via a Piloty-Robinson pyrrole synthesis. The use
      of microwave radiation for the cyclization and pyrrole formation greatly reduces
      the time necessary for this process and facilitates moderate to good yields from
      hydrazine for the corresponding 3,4-disubstituted products (5-12). By simple
      hydrolysis, the free N-H pyrroles can be accessed after the Piloty-Robinson
      reaction and then used directly in the synthesis of octaethylporphyrin (H2OEP,
      14) and octaethyltetraphenylporphyrin (H2OETPP, 15).

PMID- 17432916
TI  - A beta-keto ester as a novel, efficient, and versatile ligand for copper(I)
      catalyzed C-N, C-O, and C-S coupling reactions.
AB  - Employing ethyl 2-oxocyclohexanecarboxylate as a novel, efficient, and versatile
      ligand, the copper-catalyzed coupling reactions of various N/O/S nucleophilic
      reagents with aryl halides could be successfully carried out under mild
      conditions. A variety of products including N-arylamides, N-arylimidazoles, aryl
      ethers, and aryl thioethers were synthesized in good to excellent yields.

PMID- 17432918
TI  - Combinatorial study of the optimization of Y2O3:Bi,Eu red phosphors.
AB  - The present investigation aims at the synthesis of (Y2-xEuxBiy)O3 red phosphor
      materials using the combinatorial chemistry method. We developed square-type
      arrays consisting of 90 compositions to obtain the optimum composition of co
      dopants in a Y2O3 host. The optimized composition was found to be (Y2-xEuxBiy)O3
      (x = 0.16-0.18, y = 0.08-0.10). The screening of the compositions was
      investigated by analysis of the emission spectrum under 365 nm UV excitation
      arising from the energy transfer between Bi3+ and Eu3+ ions. The results of the
      photoluminescence excited by ultraviolet agree well with the conventional-scale
      synthesis results, indicating that the combinatorial screening method is fast,
      reliable, reproducible, and applicable to the study of powder materials with
      relatively quick calcinations at high synthesis temperatures.

PMID- 17432919
TI  - Cerium(IV) ammonium nitrate--a versatile single-electron oxidant.

PMID- 17432920
TI  - Highly tunable infrared extinction properties of gold nanocrescents.
AB  - The infrared extinction properties of gold nanocrescents fabricated using
      nanosphere template lithography were studied. The nanocrescents exhibit multiple,
      structurally tunable localized surface plasmon resonances (LSPRs) across a broad
      spectral range (560-3600 nm). Plasmon resonances in the infrared have large
      extinction efficiencies of approximately 20 and peaks as narrow as 0.07 eV. The
      nanocrescents also have high refractive index sensitivities (370-880 nm/RIU) that
      are proportional to the LSPR wavelengths. The sensing figure of merit measured
      for ensembles of nanocrescents is as high as 2.4 for near-infrared plasmon
      resonances.

PMID- 17432921
TI  - Inner-tube chirality determination for double-walled carbon nanotubes by scanning
      tunneling microscopy.
AB  - Evidence for modified electronic structure in double-walled carbon nanotubes with
      respect to their individual inner and outer constituent single-walled nanotubes
      is provided by scanning tunneling microscopy and spectroscopy experiments. The
      contribution originating from the inner tube to the local density of states of
      the double-walled system was identified in agreement with previous theoretical
      calculations. Consequently, the chiral index for the inner tube was extracted
      based on the additional van Hove singularities present in the experimental
      tunneling spectra.

PMID- 17432922
TI  - When should levodopa therapy be initiated in patients with Parkinson's disease?
AB  - Levodopa is available in three forms: immediate-release, orally disintegrating
      and sustained-release tablets. Levodopa is metabolised in the gastrointestinal
      tract, kidney and liver by aromatic acid dopa decarboxylase using pyridoxine as a
      cofactor. Approximately 70-80% of the dose is eliminated in the urine. Central
      conversion of levodopa to dopamine likely occurs at surviving dopaminergic
      terminals and at serotonergic and adrenergic nerve terminals that contain
      decarboxylase. Dopamine is metabolised by catechol-O-methyltransferase and
      monoamine oxidase. The major metabolites of dopamine are homovanillic acid and
      dihydroxyphenylacetic acid. Levodopa remains the most efficacious pharmacological
      treatment for the symptoms of Parkinson's disease (PD). Results of current
      levodopa trials suggest that treatment with levodopa at the onset of disease
      provides superior motor and functional control compared with dopamine receptor
      agonists. Moreover, levodopa is generally better tolerated with a lower incidence
      of gastrointestinal and neuropsychiatric adverse effects. The debate over the
      role of levodopa in the treatment of PD is fuelled by the results of in vitro
      studies that show generation of free radicals by levodopa and its toxic effects
      on cell cultures. Levodopa has also consistently been shown to produce motor
      fluctuations (in particular dyskinesias) sooner than has been observed in PD
      patients, especially younger patients, given dopamine agonists initially.
      However, the cumulative body of knowledge thus far does not show definitive
      evidence that levodopa is neurotoxic to parkinsonian patients. In older PD
      patients with lesser risk of motor fluctuations, levodopa may be used initially,
      and perhaps solely, in demented PD patients and those at higher risk of
      developing neuropsychiatric adverse effects. In young parkinsonian patients with
      mild motor dysfunction, use of levodopa may be delayed or the dosage minimised.
      However, because of levodopa's superior efficacy, when a rapid and sustained
      symptomatic improvement is required because of significant motor disability,
      levodopa may be used as the first-line agent regardless of age.

PMID- 17432923
TI  - Use of pharmacodynamic principles to optimise dosage regimens for antibacterial
      agents in the elderly.
AB  - Throughout most of the world we are witnessing an ever increasing number of aged
      people as a percentage of the general population. In the coming years, the unique
      spectrum of infections presented by an elderly population, particularly those in
      long-term care facilities, will challenge our ability to maintain an effective
      battery of antibacterials. The pharmacokinetic parameters of most antibacterial
      agents are altered when assessed in the elderly due in part to non-pathological
      physiological changes. The inability to clear a drug from the body due to
      declining lung, kidney/bladder, gastrointestinal and circulatory efficiency can
      cause accumulation in the body of drugs given in standard dosages. While this may
      have the potential benefit of achieving therapeutic concentrations at a lower
      dose, there is also a heightened risk of attaining toxic drug concentrations and
      an increased chance of unfavourable interactions with other medications.
      Pharmacodynamic issues in the elderly are related to problems that arise from
      treating elderly patients who may have a history of previous antibacterial
      treatment and exposure to resistant organisms from multiple hospitalisations.
      Furthermore, the elderly often acquire infections in tandem with other common
      disease states such as diabetes mellitus and heart disease. Thus, it is essential
      that optimised dosage strategies be designed specifically for this population
      using pharmacodynamic principles that take into account the unique circumstances
      of the elderly. Rational and effective dosage and administration strategies based
      on pharmacodynamic breakpoints and detailed understanding of the pharmacokinetics
      of antibacterials in the elderly increase the chances of achieving complete
      eradication of an infection in a timely manner. In addition, this strategy helps
      prevent selection of drug-resistant bacteria and minimises the toxic effects of
      antibacterial therapy in the elderly patient.

PMID- 17432924
TI  - Onychomycosis in the elderly : drug treatment options.
AB  - The prevalence of onychomycosis is nearly 20% in patients aged >60 years. In
      North America, 90% of toenail onychomycosis is caused by dermatophytes
      (Trichophyton species). Distal-lateral subungual onychomycosis is the most common
      clinical presentation. The potassium hydroxide test is the most cost-effective
      diagnostic method. Although nail clipping for histology using periodic acid
      Schiff stain is more sensitive, it is much more expensive. Elderly patients have
      specific risk factors for poor response to therapy for onychomycosis, including
      frequent nail dystrophy, slow growth of nails and increased prevalence of
      peripheral vascular disease and diabetes mellitus. Elderly people with diabetes
      should be treated for onychomycosis to prevent secondary bacterial infections and
      subsequent complications. Terbinafine is the drug of choice for dermatophyte
      onychomycosis, with greater mycological cure rates, less serious and fewer drug
      interactions, and a lower cost than continuous itraconazole therapy. Adjunct
      debridement may improve the clinical and complete cure rates compared with
      terbinafine alone. Common adverse effects of terbinafine in the elderly include
      nausea, sinusitis, arthralgia and hypercholesterolaemia. For onychomycosis caused
      by Candida or nondermatophyte moulds, there is no superior systemic therapy. In
      general, topical nail lacquers, amorolfine and ciclopirox are not practical for
      elderly patients because of the recommended frequency of application, periodic
      routine debridement of affected nails and long duration of therapy. However, nail
      lacquers may be a good option as monotherapy for patients with superficial white
      onychomycosis or in combination with systemic antifungal therapy for patients
      with predisposing factors for poor response or recurrence.

PMID- 17432926
TI  - Pharmacotherapy for nocturia in the elderly patient.
AB  - Nocturia may be attributable to nocturnal polyuria (nocturnal urine
      overproduction), a diminished nocturnal bladder capacity or a combination of the
      two conditions.A disorder of the vasopressin (antidiuretic hormone) system with
      very low or undetectable levels of vasopressin at night, affecting some elderly
      people, may cause an increase in the nocturnal urine output, which in the most
      extreme cases accounts for 85% of the 24-hour diuresis. The increased urine
      output can be treated with desmopressin orally at bedtime, generally using low
      doses. Self-imposed fluid restrictions before bedtime are not effective in
      reducing the nocturnal urine output in this condition. Nocturia is also more
      prevalent in association with a reduced bladder capacity. Antimuscarinic drugs
      are used in attempts to depress involuntary bladder contractions. Decreased
      nocturnal voided volumes in men and consequent increased nocturia may suggest
      difficulty in emptying the bladder or detrusor overactivity. alpha(1)
      Adrenoceptor antagonists and 5alpha-reductase inhibitors are often used in men
      with symptoms indicative of benign prostatic hyperplasia, and one of their
      effects is reduction of nocturia. In women, estrogen deficiency, a common
      consequence of the menopausal transition, causes atrophic changes within the
      urogenital tract. Consequently, such women are more disposed to having urogenital
      symptoms, among them nocturia. This review emphasises the importance of correctly
      diagnosing and treating nocturia in elderly patients. This will improve patients'
      sleep and, in turn, reduce their risk of fall injuries and the associated
      detrimental consequences, thereby improving patients' health and quality of life.

PMID- 17432927
TI  - Does glycoprotein IIIa gene (Pl(A)) polymorphism influence clopidogrel
      resistance? : a study in older patients.
AB  - BACKGROUND: Clopidogrel is a potent antiplatelet drug used for secondary
      prevention after ischaemic cardiovascular or cerebrovascular events. In patients
      with aspirin (acetylsalicylic acid) intolerance or resistance, it is used as
      monotherapy. Recent data report that Pl(A) polymorphism of the glycoprotein IIIa
      gene may account for differences in aspirin-induced antiplatelet effects. An
      increased degree of platelet reactivity was also reported in Pl(A2) carriers
      compared with Pl(A1/A1) patients after administration of a clopidogrel 300mg
      loading dose. OBJECTIVES: The aim of this study was to assess the modulatory
      effect of the Pl(A2) allele on platelet aggregation in patients taking long-term
      clopidogrel. M ETHODS: The prevalence of the Pl(A2) allele was assessed in 38 (21
      males, 17 females; mean age 63 +/- 13 years) clopidogrel-resistant and 59 (26
      males, 33 females; mean age 63 +/- 11 years) clopidogrel-responsive patients. The
      polymerase chain reaction-restriction fragment length polymorphism method was
      utilised to evaluate Pl(A) polymorphism. A Carat TX4 optical platelet
      aggregometer (Carat Diagnostics Ltd, Budapest, Hungary) was used to measure 5 and
      10 micromol/L adenosine diphosphate-induced platelet aggregation. RESULTS:
      Significantly more patients were taking combination antiplatelet therapy in the
      clopidogrel-resistant group than in the clopidogrel-responsive group (50% vs 30%,
      respectively). The prevalence of the Pl(A2) allele did not differ significantly
      between the two groups (0.09 vs 0.13), even after adjustment for combination
      therapy and various risk factors. CONCLUSIONS: Our results show that carriers of
      the Pl(A2) allele do not have an increased risk of clopidogrel resistance. These
      findings and data from our previous studies suggest that patients with a Pl(A2)
      allele homozygosity may benefit from antiplatelet therapy based on clopidogrel
      rather than aspirin.

PMID- 17432925
TI  - Management of acute exacerbations of chronic obstructive pulmonary disease in the
      elderly : an appraisal of published evidence.
AB  - Chronic obstructive pulmonary disease (COPD) is a debilitating disease with
      rising worldwide prevalence. Exacerbations of COPD cause significant morbidity
      and become more common with advancing age. Healthcare providers caring for
      elderly patients should therefore be familiar with effective treatments for
      exacerbations of COPD. An extensive body of literature has identified several
      effective drug therapies for exacerbations. These drugs include inhaled
      bronchodilators, systemic corticosteroids and antibacterials. The two main
      classes of inhaled bronchodilators are beta-adrenoceptor agonists and
      anticholinergics. These drugs optimise lung function during exacerbations, with
      neither class demonstrating clear superiority over the other. Systemic
      corticosteroids are effective when used either for inpatient or outpatient
      treatment of exacerbations. They hasten recovery from exacerbations and reduce
      relapse rates. Antibacterials decrease morbidity from exacerbations and may
      decrease mortality in the more severe exacerbations. Other effective therapies
      for the treatment of acute exacerbations of COPD include oxygen and non-invasive
      ventilation. Oxygen can be safely administered in acute exacerbations associated
      with hypoxaemia, with titration of oxygen delivery to a goal oxygen saturation of
      90%. Non-invasive ventilation reduces the morbidity and mortality associated with
      acute exacerbations complicated by hypercapnic respiratory failure. Strategies to
      prevent COPD exacerbations include smoking cessation, long-acting inhaled beta
      adrenoceptor agonists, inhaled long-acting anticholinergics, inhaled
      corticosteroids and vaccination. Mucolytic agents, pulmonary rehabilitation, and
      case management programmes may also reduce exacerbation risk, but the current
      evidence supporting these interventions is weaker.

PMID- 17432928
TI  - Cell size at S phase initiation: an emergent property of the G1/S network.
AB  - The eukaryotic cell cycle is the repeated sequence of events that enable the
      division of a cell into two daughter cells. It is divided into four phases: G1,
      S, G2, and M. Passage through the cell cycle is strictly regulated by a molecular
      interaction network, which involves the periodic synthesis and destruction of
      cyclins that bind and activate cyclin-dependent kinases that are present in
      nonlimiting amounts. Cyclin-dependent kinase inhibitors contribute to cell cycle
      control. Budding yeast is an established model organism for cell cycle studies,
      and several mathematical models have been proposed for its cell cycle. An area of
      major relevance in cell cycle control is the G1 to S transition. In any given
      growth condition, it is characterized by the requirement of a specific, critical
      cell size, PS, to enter S phase. The molecular basis of this control is still
      under discussion. The authors report a mathematical model of the G1 to S network
      that newly takes into account nucleo/cytoplasmic localization, the role of the
      cyclin-dependent kinase Sic1 in facilitating nuclear import of its cognate Cdk1
      Clb5, Whi5 control, and carbon source regulation of Sic1 and Sic1-containing
      complexes. The model was implemented by a set of ordinary differential equations
      that describe the temporal change of the concentration of the involved proteins
      and protein complexes. The model was tested by simulation in several genetic and
      nutritional setups and was found to be neatly consistent with experimental data.
      To estimate PS, the authors developed a hybrid model including a probabilistic
      component for firing of DNA replication origins. Sensitivity analysis of PS
      provides a novel relevant conclusion: PS is an emergent property of the G1 to S
      network that strongly depends on growth rate.

PMID- 17432929
TI  - Inferring noncoding RNA families and classes by means of genome-scale structure
      based clustering.
AB  - The RFAM database defines families of ncRNAs by means of sequence similarities
      that are sufficient to establish homology. In some cases, such as microRNAs and
      box H/ACA snoRNAs, functional commonalities define classes of RNAs that are
      characterized by structural similarities, and typically consist of multiple RNA
      families. Recent advances in high-throughput transcriptomics and comparative
      genomics have produced very large sets of putative noncoding RNAs and regulatory
      RNA signals. For many of them, evidence for stabilizing selection acting on their
      secondary structures has been derived, and at least approximate models of their
      structures have been computed. The overwhelming majority of these hypothetical
      RNAs cannot be assigned to established families or classes. We present here a
      structure-based clustering approach that is capable of extracting putative RNA
      classes from genome-wide surveys for structured RNAs. The LocARNA (local
      alignment of RNA) tool implements a novel variant of the Sankoff algorithm that
      is sufficiently fast to deal with several thousand candidate sequences. The
      method is also robust against false positive predictions, i.e., a contamination
      of the input data with unstructured or nonconserved sequences. We have
      successfully tested the LocARNA-based clustering approach on the sequences of the
      RFAM-seed alignments. Furthermore, we have applied it to a previously published
      set of 3,332 predicted structured elements in the Ciona intestinalis genome
      (Missal K, Rose D, Stadler PF (2005) Noncoding RNAs in Ciona intestinalis.
      Bioinformatics 21 (Supplement 2): i77-i78). In addition to recovering, e.g.,
      tRNAs as a structure-based class, the method identifies several RNA families,
      including microRNA and snoRNA candidates, and suggests several novel classes of
      ncRNAs for which to date no representative has been experimentally characterized.

PMID- 17432930
TI  - Synchronization-induced rhythmicity of circadian oscillators in the
      suprachiasmatic nucleus.
AB  - The suprachiasmatic nuclei (SCN) host a robust, self-sustained circadian
      pacemaker that coordinates physiological rhythms with the daily changes in the
      environment. Neuronal clocks within the SCN form a heterogeneous network that
      must synchronize to maintain timekeeping activity. Coherent circadian output of
      the SCN tissue is established by intercellular signaling factors, such as
      vasointestinal polypeptide. It was recently shown that besides coordinating
      cells, the synchronization factors play a crucial role in the sustenance of
      intrinsic cellular rhythmicity. Disruption of intercellular signaling abolishes
      sustained rhythmicity in a majority of neurons and desynchronizes the remaining
      rhythmic neurons. Based on these observations, the authors propose a model for
      the synchronization of circadian oscillators that combines intracellular and
      intercellular dynamics at the single-cell level. The model is a heterogeneous
      network of circadian neuronal oscillators where individual oscillators are damped
      rather than self-sustained. The authors simulated different experimental
      conditions and found that: (1) in normal, constant conditions, coupled circadian
      oscillators quickly synchronize and produce a coherent output; (2) in large
      populations, such oscillators either synchronize or gradually lose rhythmicity,
      but do not run out of phase, demonstrating that rhythmicity and synchrony are
      codependent; (3) the number of oscillators and connectivity are important for
      these synchronization properties; (4) slow oscillators have a higher impact on
      the period in mixed populations; and (5) coupled circadian oscillators can be
      efficiently entrained by light-dark cycles. Based on these results, it is
      predicted that: (1) a majority of SCN neurons needs periodic synchronization
      signal to be rhythmic; (2) a small number of neurons or a low connectivity
      results in desynchrony; and (3) amplitudes and phases of neurons are negatively
      correlated. The authors conclude that to understand the orchestration of
      timekeeping in the SCN, intracellular circadian clocks cannot be isolated from
      their intercellular communication components.

PMID- 17432931
TI  - Increasing the power to detect causal associations by combining genotypic and
      expression data in segregating populations.
AB  - To dissect common human diseases such as obesity and diabetes, a systematic
      approach is needed to study how genes interact with one another, and with genetic
      and environmental factors, to determine clinical end points or disease
      phenotypes. Bayesian networks provide a convenient framework for extracting
      relationships from noisy data and are frequently applied to large-scale data to
      derive causal relationships among variables of interest. Given the complexity of
      molecular networks underlying common human disease traits, and the fact that
      biological networks can change depending on environmental conditions and genetic
      factors, large datasets, generally involving multiple perturbations
      (experiments), are required to reconstruct and reliably extract information from
      these networks. With limited resources, the balance of coverage of multiple
      perturbations and multiple subjects in a single perturbation needs to be
      considered in the experimental design. Increasing the number of experiments, or
      the number of subjects in an experiment, is an expensive and time-consuming way
      to improve network reconstruction. Integrating multiple types of data from
      existing subjects might be more efficient. For example, it has recently been
      demonstrated that combining genotypic and gene expression data in a segregating
      population leads to improved network reconstruction, which in turn may lead to
      better predictions of the effects of experimental perturbations on any given
      gene. Here we simulate data based on networks reconstructed from biological data
      collected in a segregating mouse population and quantify the improvement in
      network reconstruction achieved using genotypic and gene expression data,
      compared with reconstruction using gene expression data alone. We demonstrate
      that networks reconstructed using the combined genotypic and gene expression data
      achieve a level of reconstruction accuracy that exceeds networks reconstructed
      from expression data alone, and that fewer subjects may be required to achieve
      this superior reconstruction accuracy. We conclude that this integrative genomics
      approach to reconstructing networks not only leads to more predictive network
      models, but also may save time and money by decreasing the amount of data that
      must be generated under any given condition of interest to construct predictive
      network models.

PMID- 17432933
TI  - Molecular basis for a lack of correlation between viral fitness and cell killing
      capacity.
AB  - The relationship between parasite fitness and virulence has been the object of
      experimental and theoretical studies often with conflicting conclusions. Here, we
      provide direct experimental evidence that viral fitness and virulence, both
      measured in the same biological environment provided by host cells in culture,
      can be two unrelated traits. A biological clone of foot-and-mouth disease virus
      acquired high fitness and virulence (cell killing capacity) upon large population
      passages in cell culture. However, subsequent plaque-to-plaque transfers resulted
      in profound fitness loss, but only a minimal decrease of virulence. While fitness
      decreasing mutations have been mapped throughout the genome, virulence
      determinants-studied here with mutant and chimeric viruses-were multigenic, but
      concentrated on some genomic regions. Therefore, we propose a model in which
      viral virulence is more robust to mutation than viral fitness. As a consequence,
      depending on the passage regime, viral fitness and virulence can follow different
      evolutionary trajectories. This lack of correlation is relevant to current models
      of attenuation and virulence in that virus de-adaptation need not entail a
      decrease of virulence.

PMID- 17432932
TI  - Transcriptional regulation of chemical diversity in Aspergillus fumigatus by
      LaeA.
AB  - Secondary metabolites, including toxins and melanins, have been implicated as
      virulence attributes in invasive aspergillosis. Although not definitively proved,
      this supposition is supported by the decreased virulence of an Aspergillus
      fumigatus strain, DeltalaeA, that is crippled in the production of numerous
      secondary metabolites. However, loss of a single LaeA-regulated toxin, gliotoxin,
      did not recapitulate the hypovirulent DeltalaeA pathotype, thus implicating other
      toxins whose production is governed by LaeA. Toward this end, a whole-genome
      comparison of the transcriptional profile of wild-type, DeltalaeA, and
      complemented control strains showed that genes in 13 of 22 secondary metabolite
      gene clusters, including several A. fumigatus-specific mycotoxin clusters, were
      expressed at significantly lower levels in the DeltalaeA mutant. LaeA influences
      the expression of at least 9.5% of the genome (943 of 9,626 genes in A.
      fumigatus) but positively controls expression of 20% to 40% of major classes of
      secondary metabolite biosynthesis genes such as nonribosomal peptide synthetases
      (NRPSs), polyketide synthases, and P450 monooxygenases. Tight regulation of NRPS
      encoding genes was highlighted by quantitative real-time reverse-transcription
      PCR analysis. In addition, expression of a putative siderophore biosynthesis NRPS
      (NRPS2/sidE) was greatly reduced in the DeltalaeA mutant in comparison to
      controls under inducing iron-deficient conditions. Comparative genomic analysis
      showed that A. fumigatus secondary metabolite gene clusters constitute
      evolutionarily diverse regions that may be important for niche adaptation and
      virulence attributes. Our findings suggest that LaeA is a novel target for
      comprehensive modification of chemical diversity and pathogenicity.

PMID- 17432934
TI  - Rev proteins of human and simian immunodeficiency virus enhance RNA
      encapsidation.
AB  - The main function attributed to the Rev proteins of immunodeficiency viruses is
      the shuttling of viral RNAs containing the Rev responsive element (RRE) via the
      CRM-1 export pathway from the nucleus to the cytoplasm. This restricts expression
      of structural proteins to the late phase of the lentiviral replication cycle.
      Using Rev-independent gag-pol expression plasmids of HIV-1 and simian
      immunodeficiency virus and lentiviral vector constructs, we have observed that
      HIV-1 and simian immunodeficiency virus Rev enhanced RNA encapsidation 20- to 70
      fold, correlating well with the effect of Rev on vector titers. In contrast,
      cytoplasmic vector RNA levels were only marginally affected by Rev. Binding of
      Rev to the RRE or to a heterologous RNA element was required for Rev-mediated
      enhancement of RNA encapsidation. In addition to specific interactions of
      nucleocapsid with the packaging signal at the 5' end of the genome, the Rev/RRE
      system provides a second mechanism contributing to preferential encapsidation of
      genomic lentiviral RNA.

PMID- 17432935
TI  - Multiple-pathway analysis of double-strand break repair mutations in Drosophila.
AB  - The analysis of double-strand break (DSB) repair is complicated by the existence
      of several pathways utilizing a large number of genes. Moreover, many of these
      genes have been shown to have multiple roles in DSB repair. To address this
      complexity we used a repair reporter construct designed to measure multiple
      repair outcomes simultaneously. This approach provides estimates of the relative
      usage of several DSB repair pathways in the premeiotic male germline of
      Drosophila. We applied this system to mutations at each of 11 repair loci plus
      various double mutants and altered dosage genotypes. Most of the mutants were
      found to suppress one of the pathways with a compensating increase in one or more
      of the others. Perhaps surprisingly, none of the single mutants suppressed more
      than one pathway, but they varied widely in how the suppression was compensated.
      We found several cases in which two or more loci were similar in which pathway
      was suppressed while differing in how this suppression was compensated. Taken as
      a whole, the data suggest that the choice of which repair pathway is used for a
      given DSB occurs by a two-stage "decision circuit" in which the DSB is first
      placed into one of two pools from which a specific pathway is then selected.

PMID- 17432937
TI  - Retrotransposon silencing by DNA methylation can drive mammalian genomic
      imprinting.
AB  - Among mammals, only eutherians and marsupials are viviparous and have genomic
      imprinting that leads to parent-of-origin-specific differential gene expression.
      We used comparative analysis to investigate the origin of genomic imprinting in
      mammals. PEG10 (paternally expressed 10) is a retrotransposon-derived imprinted
      gene that has an essential role for the formation of the placenta of the mouse.
      Here, we show that an orthologue of PEG10 exists in another therian mammal, the
      marsupial tammar wallaby (Macropus eugenii), but not in a prototherian mammal,
      the egg-laying platypus (Ornithorhynchus anatinus), suggesting its close
      relationship to the origin of placentation in therian mammals. We have discovered
      a hitherto missing link of the imprinting mechanism between eutherians and
      marsupials because tammar PEG10 is the first example of a differentially
      methylated region (DMR) associated with genomic imprinting in marsupials.
      Surprisingly, the marsupial DMR was strictly limited to the 5' region of PEG10,
      unlike the eutherian DMR, which covers the promoter regions of both PEG10 and the
      adjacent imprinted gene SGCE. These results not only demonstrate a common origin
      of the DMR-associated imprinting mechanism in therian mammals but provide the
      first demonstration that DMR-associated genomic imprinting in eutherians can
      originate from the repression of exogenous DNA sequences and/or retrotransposons
      by DNA methylation.

PMID- 17432938
TI  - Isolation and molecular characterization of a porcine teschovirus 1 isolate from
      China.
AB  - Porcine teschovirus 1 (PTV-1) (Swine/CH/IMH/03) was isolated from piglets in a
      farm in Inner Mongolia Province, P.R. China. It was confirmed by electron
      microscopy, RT-PCR, and sequencing. Comparison of the sequences of the amino acid
      and nucleotides and phylogenetic analysis of the polyprotein showed that PTV
      Swine/CH/IMH/03 strain is PTV-1. The isolated virus has closest relationship with
      Talfan strain, they shared 98.9% and 99.5% homology of amino acids and
      nucleotides, respectively, in the ORF of polyprotein. To our knowledge, this is
      the first report about isolation and identification of a PTV in China.

PMID- 17432939
TI  - Reactivation of latent human immunodeficiency virus 1 by human herpesvirus 6
      infection.
AB  - Infection of the ACH-2 line of human leukemic T cells carrying latent Human
      immunodeficiency virus 1 (HIV-1) with Human herpesvirus 6 (HHV-6) resulted in an
      increase in reverse transcriptase (RT) activity, a marker of HIV-1 activation, in
      the culture supernatant. A similar effect was obtained with 12-O-tetradecanoyl
      phorbol-13-acetate (TPA). The RT activity reached a peak at 24 hrs post infection
      (p.i.) and then declined, suggesting that the cells underwent lysis. The HIV-1
      antigen was co-expressed with an early-late HHV-6 product, but not always with an
      immediate-early (IE) HHV-6 product, suggesting that one or more IE gene products
      were involved in the activation of latent HIV-1 in ACH-2 cells.

PMID- 17432936
TI  - A tale of two oxidation states: bacterial colonization of arsenic-rich
      environments.
AB  - Microbial biotransformations have a major impact on contamination by toxic
      elements, which threatens public health in developing and industrial countries.
      Finding a means of preserving natural environments-including ground and surface
      waters-from arsenic constitutes a major challenge facing modern society. Although
      this metalloid is ubiquitous on Earth, thus far no bacterium thriving in arsenic
      contaminated environments has been fully characterized. In-depth exploration of
      the genome of the beta-proteobacterium Herminiimonas arsenicoxydans with regard
      to physiology, genetics, and proteomics, revealed that it possesses heretofore
      unsuspected mechanisms for coping with arsenic. Aside from multiple biochemical
      processes such as arsenic oxidation, reduction, and efflux, H. arsenicoxydans
      also exhibits positive chemotaxis and motility towards arsenic and metalloid
      scavenging by exopolysaccharides. These observations demonstrate the existence of
      a novel strategy to efficiently colonize arsenic-rich environments, which extends
      beyond oxidoreduction reactions. Such a microbial mechanism of detoxification,
      which is possibly exploitable for bioremediation applications of contaminated
      sites, may have played a crucial role in the occupation of ancient ecological
      niches on earth.

PMID- 17432940
TI  - An intrastrain variation of a 189-bp repeat region in the human cytomegalovirus
      replication origin.
AB  - A 189-bp repeat has been reported previously to be present in the replication
      origin (ORI) of Human cytomegalovirus (HCMV) Towne strain and to contain
      essential and supporting sequences (Chen et al., Arch. Virol. 141, 13301 (1996)).
      In this study, clones of HCMV strain Towne were isolated and analyzed for the
      copy number of the 189-bp repeat within its ORI (oriLyt). Southern blot analysis
      revealed that out of 14 clones, two contained a dimer, two contained a tetramer,
      and the remaining contained a trimer of the 189-bp repeat. Nucleotide sequence
      analysis disclosed that, within the dimer and the tetramer, the 189-bp repeat was
      present in a directly repeated manner. In this way we demonstrated an HCMV
      intrastrain variation in the copy number of the 189-bp repeat. Dot blot
      hybridization and growth curve analysis showed that the clones containing the
      dimer or the tetramer replicated in infected cells with similar efficiencies. We
      conclude that the HCMV oriLyt with spatial separation of the essential flanking
      regions by various copy number of the 189-bp repeat acts as ORI in the viral
      genome.

PMID- 17432941
TI  - Pathogenesis and antibody response to a cytomegalovirus infection in newborn
      rats.
AB  - The present study described the kinetics of Rat cytomegalovirus (RCMV) infection
      in newborn rats by monitoring infectious virus and viral antigens in various
      organs, viral DNA in the blood (DNAemia) and antibody response. These parameters
      were evaluated quantitatively using double-antibody sandwich ELISA (DAS-ELISA),
      real-time PCR, indirect ELISA and virus infectivity assay. For the first time DAS
      ELISA was used for detection of RCMV antigen directly from organ samples. The
      relationships between the presence of viral antigens in the infected organs and
      antibody levels were established by the Spearman's rank test. It was found that
      the virus was present in the blood, spleen, liver, lungs, and kidneys earlier
      than in the salivary glands. Furthermore, the early immunity of the newborn rats
      led to a delayed seroconversion. We suggested that the prolonged presence of the
      virus in salivary glands could augment the antibody response that conversely
      might be responsible for a reduction of viremia. This study expanded our
      understanding of RCMV pathogenesis leading to improved therapeutic and preventive
      treatment regimens particularly for the neonatal Human cytomegalovirus (HCMV)
      infections. Additionally, the detection procedures developed in this study such
      as DAS-ELISA and real-time PCR could serve as alternative techniques for rapid
      screening of large number of samples.

PMID- 17432943
TI  - B5r gene based sequence analysis of Indian buffalopox virus isolates in relation
      to other orthopoxviruses.
AB  - We determined complete nucleotide sequence of B5R gene homologue of Vaccinia
      virus (VACV) in five Buffalopox virus (BPXV) isolates of Indian origin. The
      obtained sequences were compared with themselves and with corresponding sequences
      of the other orthopoxviruses. Sequence analysis revealed 99.799.8% and 99.499.7%
      identities among the BPXV isolates for B5R gene at the nucleotide and amino acid
      levels, respectively. Sequence identities of B5R gene between BPXV and VACV
      isolates (98.199.7%) or other orthopoxviruses (95.699.2%) showed highly conserved
      nature of this protein and a closer relationship of BPXV isolates to VACV than to
      other orthopoxviruses.

PMID- 17432942
TI  - Immune and protective abilities of ubiquitinated and non-ubiquitinated
      pseudorabies virus glycoproteins.
AB  - Plasmids encoding ubiquitinated (ubi-) or non-ubiquitinated (non-ubi-)
      glycoproteins of Pseudorabies virus (PRV) were used for vaccination of pigs. We
      found that the fusion of ubiquitin to viral glycoproteins increased their
      degradation in proteasomes in vitro, in which ubiquitin plays a key role. In the
      animals immunized with the plasmids encoding PRV ubi-glycoproteins and then
      challenged with PRV, we detected a slightly decreased cellular immune response on
      days 13 and 19 after immunization and a reduced nasal excretion of infectious
      virus on day 2 after the challenge. Afterwards, no effect of the ubiquitination
      of the glycoproteins on humoral or cellular immunity and on excretion of
      infectious virus was observed. Similarly, no effect of the ubiquitination on
      protective abilities of PRV glycoproteins was found.

PMID- 17432944
TI  - A novel double-stable T-REx/gb cell line expressing glycoprotein B of herpes
      simplex virus 1.
AB  - We established and characterized a new stable T-REx/gB cell line expressing gB of
      HSV-1 under tetracycline (Tet) control. The expression of complete gB (120 K) in
      T-REx/gB cells was detected by Western blot analysis with anti-HSV-1/ANG/gB
      monoclonal antibody as early as 2 days after Tet induction. Inducibility and
      tightness of Tet-regulated gB expression in T-REx/gB cell line was shown to be
      preserved after long-term culture (2 months) and after numerous freezing/thawing
      cycles as well. In this study, we described the conditions required for the
      generation of the T-REx/gB cell line, which can be useful as a host for the
      isolation and propagation of HSV-1 recombinant viruses defective in gB gene.

PMID- 17432945
TI  - Detection of specific spectral markers of Coxiella burnetii isolates by MALDI-TOF
      mass spectrometry.
AB  - Specific markers for Coxiella burnetii (C.b.) isolates RSA 493, Priscilla, and
      BUD were detected using matrix-assisted laser desorption/ionization time-of
      flight (MALDI-TOF) mass spectrometry (MS). The method revealed noticeable
      differences in the ion signal profiles of the isolates in the mass range of 318
      kDa. The number of characteristic ions for RSA 493, BUD, and Priscilla was 24,
      15, and 7, respectively. The specific markers were compared against C.b. database
      using the Tag-Ident proteomics tool. For the isolates RSA 493, Priscilla and BUD
      there were identified 11, 5 and 3 potential biomarkers, respectively. This method
      represents a powerful tool for the rapid, sensitive, and differential
      characterization of C.b. isolates and is a good candidate for phyloproteomic
      approaches.

PMID- 17432946
TI  - HIV-1-specific CD8(+) T cells do not correlate with viral load in HIV-1-positive
      patients.

PMID- 17432947
TI  - Detection of influenza a virus in wild birds in West Slovakia by nested PCR.

PMID- 17432948
TI  - Sequence analysis of the M genome segment of two Seoul virus isolates from
      Shandong Province, China.

PMID- 17432949
TI  - Detection of Ehrlichia muris in a yellow-necked mouse (Apodemus flavicollis) in
      Central Slovakia.

PMID- 17432950
TI  - The in vitro expression and secretion of vascular endothelial growth factor from
      free and alginate-polyornithine encapsulated choroid plexus epithelium.
AB  - The choroid plexus (CP) is a transplantable cell source secreting tropic and
      trophic factors for the treatment of brain and peripheral trauma characterized by
      cellular loss or dysfunction. Here we characterize the expression and secretion
      of vascular endothelial growth factor (VEGF) from neonatal porcine CP. Light and
      electron microscopy revealed that enzymatic digestion of the CP produced a
      preparation consisting primarily of epithelial cells without notable
      contaminating cells. Microarray analysis, quantitative polymerase chain reaction,
      and enzyme-linked immunosorbent assay were used to quantify the nuclear,
      cytoplasmic, and secretory compartmentalization of VEGF. In vitro, the kinetics
      of VEGF release were orderly, with stepwise increases in secretion over time. The
      secretory profile of VEGF from CP grown in configurations ranging from a simple
      monolayer to free-floating 3-dimensional clusters to clusters encapsulated within
      alginate-polyornithine microcapsules was similar. VEGF output was not affected
      notably when the cells were maintained in 90% stress medium or in other
      maintenance media devoid of serum proteins. Secreted VEGF was bioactive, as
      confirmed by demonstrating its continued ability to proliferate co-cultured human
      umbilical vascular endothelial cells. The robust ability of these cells to
      continue to secrete VEGF (and presumably other bioactive proteins) across a
      variety of dimensional configurations and medium types has implications for their
      use in clinical indications requiring novel and imaginative use of engineered
      ectopic transplant sites.

PMID- 17432952
TI  - BioStar 2006 2nd International Congress on Regenerative Biology and ICBN 2006 2nd
      International Congress on Bio-Nano-Interface, October 9-11, 2006, Stuttgart,
      Germany. Abstracts.

PMID- 17432951
TI  - Isolation and characterization of postnatal stem cells from human dental tissues.
AB  - It was reported that postnatal stem cells are present in adult tissues such as
      bone marrow, liver, muscle, dental pulp, and periodontal ligament. We isolated
      postnatal stem cells from human dental tissues such as dental pulp (DPSC),
      periodontal ligament (PDLSC), periapical follicle (PAFSC), and the surrounding
      mandibular bone marrow (MBMSC) to ascertain their properties. Immunocytochemistry
      proved the existence of stem cells in these cell populations using STRO-1 as a
      stem cell marker. These cells also expressed the mesenchymal stem cell (MSC)
      markers CD29 and CD44. The isolated cells showed self-renewal capabilities and
      colony-forming efficiency. Almost all of the dental stem cells showed optimal
      growth when they were cultured in alpha modification of Eagle's medium (alpha
      MEM) supplemented with 10% fetal calf serum (FCS) and 100 microM ascorbic acid.
      Only the PAFSC showed increased proliferation in 20% FCS and 50 microM ascorbic
      acid. All of the dental stem cells were capable of differentiating into
      adipocytes and mineral nodule forming cells. MBMSC, in particular, showed much
      better mineralization compared to the others. These results indicate that MSCs
      exist in various tissues of the teeth and can differentiate into osteoblasts,
      adipocytes, and other kinds of cells with varying efficiency.

PMID- 17432953
TI  - Recombinant production of antimicrobial peptides in heterologous microbial
      systems.
AB  - The emergence and rapid horizontal spread of antibiotic-resistant traits in
      bacteria of human and veterinary clinical significance has been a driving force
      in the search for new classes of antibiotics. Recent studies have shown that AMPs
      (antimicrobial peptides) potentially have a role in addressing this problem.
      These AMPs are produced naturally by a diverse array of organisms, including
      bacteria, plants, insects, fish and mammals. Given this diversity, researchers
      trying to perform comparative studies on AMPs are likely to encounter
      difficulties in obtaining workable quantities of peptide. Such studies are
      required for optimization of antimicrobial activity, product stability, mode of
      delivery and industrial-scale production, and are vital if these peptides are
      ever to be brought to the market. Recombinant expression of AMPs is one hope for
      producing suitable amounts of diverse peptides. Here we review the literature
      regarding microbial heterologous expression systems for the production of
      recombinant AMPs.

PMID- 17432954
TI  - Phospholipase C-gamma1 is required for the activation of store-operated Ca2+
      channels in liver cells.
AB  - Repetitive hormone-induced changes in concentration of free cytoplasmic Ca2+ in
      hepatocytes require Ca2+ entry through receptor-activated Ca2+ channels and SOCs
      (store-operated Ca2+ channels). SOCs are activated by a decrease in Ca2+
      concentration in the intracellular Ca2+ stores, but the molecular components and
      mechanisms are not well understood. Some studies with other cell types suggest
      that PLC-gamma (phospholipase C-gamma) is involved in the activation of receptor
      activated Ca2+ channels and/or SOCs, independently of PLC-gamma-mediated
      generation of IP3 (inositol 1,4,5-trisphosphate). The nature of the Ca2+ channels
      regulated by PLC-gamma has not been defined clearly. The aim of the present study
      was to determine if PLC-gamma is required for the activation of SOCs in liver
      cells. Transfection of H4IIE cells derived from rat hepatocytes with siRNA (short
      interfering RNA) targeted to PLC-gamma1 caused a reduction (by approx. 70%) in
      the PLC-gamma1 protein expression, with maximal effect at 72-96 h. This was
      associated with a decrease (by approx. 60%) in the amplitude of the I(SOC) (store
      operated Ca2+ current) developed in response to intracellular perfusion with
      either IP(3) or thapsigargin. Knockdown of STIM1 (stromal interaction molecule
      type 1) by siRNA also resulted in a significant reduction (approx. 80% at 72 h
      post-transfection) of the I(SOC) amplitude. Immunoprecipitation of PLC-gamma1 and
      STIM1, however, suggested that under the experimental conditions these proteins
      do not interact with each other. It is concluded that the PLC-gamma1 protein,
      independently of IP3 generation and STIM1, is required to couple endoplasmic
      reticulum Ca2+ release to the activation of SOCs in the plasma membrane of H4IIE
      liver cells.

PMID- 17432955
TI  - Activity regulates the expression of AMPA receptor subunit GluR4 in developing
      visual cortex.
AB  - In the developing visual cortex, the expression of alpha-amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid receptor (AMPAR) subunit GluR4 precedes that of the
      other AMPAR subunits GluR1-3, and then declines to become almost absent in
      adults. The current study shows that the neuronal activity regulates the
      expression of GluR4 by a culture system in vitro and a dark-rearing (DR) system
      in vivo. Membrane depolarization by treatment of cultured neurons of the visual
      cortex with a high concentration of KCl (35 mm; HK) promoted a decline in the
      expression of GluR4. This effect of HK on the expression of GluR4 was
      significantly blocked by the addition of an N-methyl-d-aspartate receptor (NMDAR)
      antagonist, (D)-2-amino-5-phosphonovaleric acid (APV), but not by the voltage
      sensitive calcium channel antagonist nifedipine. Moreover, the Ca(2+)-calmodulin
      dependent kinase (CaMKII) inhibitor KN62 and the cAMP-dependent protein kinase A
      (PKA) inhibitor H-89 blocked this effect, which suggests the involvement of
      Ca(2+) influx via NMDAR and the subsequent activation of CaMKII and PKA.
      Conversely, the MAP kinase inhibitor PD98059 promoted the effect of HK on the
      expression of GluR4. Significantly, APV, KN62, H-89 and PD98059 either promoted
      or inhibited the expression of GluR4 even in normal KCl (5 mm) conditions. The
      developmental change in the expression of GluR4 was significantly attenuated in
      DR in vivo, and the results suggest that neuronal activity such as visual
      experience may be involved in the mechanism of the expression of GluR4, which is
      mediated by NMDAR and tuned by certain protein kinases at an early developmental
      stage in the visual cortex.

PMID- 17432956
TI  - Brain-derived neurotrophic factor modulates cell excitability in the mouse medial
      nucleus of the trapezoid body.
AB  - Neurotrophins are a large class of trophic factors located throughout the central
      nervous system. While the role of neurotrophins in neuronal survival and axon
      guidance is well known, their secondary role in modulating synaptic transmission
      and cell firing properties is largely unexplored. In this study we examined the
      expression of neurotrophins in the mouse medial nucleus of the trapezoid body
      (MNTB) and investigated the effect of exogenous brain-derived neurotrophic factor
      (BDNF) application on the firing properties of MNTB principal cells. The
      expression levels of nerve growth factor, BDNF, neurotrophin-3, neurotrophin-4/5
      and major receptor tyrosine kinase B was found to be moderate to high at
      postnatal day 12, indicating that the neurotrophins may have a role following
      synaptogenesis. A 2-h exposure to exogenous BDNF (100 ng/mL) had a significant
      effect on principal cell firing properties and voltage-gated potassium currents.
      Importantly, preincubation in BDNF increased the incidence of multifiring and
      rebounding cells, and significantly increased the number of action potentials
      fired in response to a single depolarizing step. BDNF exposure also significantly
      decreased underlying voltage-gated potassium currents, including both the low-
      and high-voltage-activated components. Our data show that the neurotrophins,
      specifically BDNF, may have a novel role in modulating cell excitability in the
      auditory brainstem.

PMID- 17432957
TI  - Differential expression of nuclear lamin, the major component of nuclear lamina,
      during neurogenesis in two germinal regions of adult rat brain.
AB  - Lamins are major structural proteins of the nuclear envelope. Three lamin
      subtypes, A/C, B1 and B2, predominate in mammalian somatic cells. While the
      expression levels of lamins in several tissues are known to change during cell
      differentiation, lamin expression is poorly understood in the nervous system. To
      investigate the expression of lamins during neuronal differentiation in the
      mammalian adult brain, we performed immunohistochemical studies on lamins A/C, B1
      and B2 in two neurogenic regions of rat brain: the subgranular zone of the
      dentate gyrus and the subventricular zone of the lateral ventricle. In
      particular, three types of cells were analysed using confocal microscopy: GFAP
      positive cells as primary progenitor (stem) cells, PSA-NCAM-positive cells as
      subsequent neuronal progenitor cells, and NeuN-positive mature neurons. GFAP
      positive cells possesed lamin A/C (++), B1 (++) and B2 (++), PSA-NCAM-positive
      cells possessed lamin A/C (-), B1 (+++) and B2 (+), and mature neurons possessed
      lamin A/C (++), B1 (+) and B2 (+++), in both neurogenic regions. These
      observations showed that the compositions of expressing lamin subtypes are
      distinct in particular differentiation stages during neurogenesis in the adult
      rat brain. Our results suggest that the alteration of nuclear lamina structure is
      coupled with the progression of neuronal differentiation.

PMID- 17432958
TI  - Metabolic progression markers of neurodegeneration in the transgenic G93A-SOD1
      mouse model of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by a progressive loss of motor neurons. Visualizing corresponding
      metabolic changes in the brain of patients with ALS with proton magnetic
      resonance spectroscopy ((1)H-MRS) may provide surrogate markers for an early
      disease detection, for monitoring the progression and for evaluating a treatment
      response. The primary objective of our study was to evaluate whether
      modifications in MR metabolite levels occur before clinical disease onset, and
      whether these changes are directly linked to a distinct spatial progression
      pattern in the CNS. Therefore, age-dependent alterations in the cerebral and
      spinal metabolic profile in the mouse model of ALS overexpressing the mutated
      human G93A-superoxide dismutase 1 (G93A-SOD1) were determined by high-resolution
      MRS of tissue extracts at 14.1 Tesla. Both non-transgenic mice (control mice) and
      transgenic mice overexpressing the non-mutated human SOD1 (tg-SOD1) served as
      controls. In the spinal cord of G93A-SOD1 mice significantly decreased levels of
      N-acetyl aspartate were already detected 34 days postpartum, i.e. about 60 days
      before the average disease onset caused by motor neuron decline. In addition,
      glutamine and gamma-aminobutyric acid concentrations were significantly
      diminished at Day 75, which is still in the presymptomatic phase of the disease.
      These metabolic changes were further progressive in the course of the disease and
      started to involve the brainstem at Day 75. Overall, high-resolution (1)H-MRS
      allows a sensitive spatial and temporal metabolite profiling in the
      presymptomatic phase of ALS even before significant neuronal cell loss occurs.

PMID- 17432959
TI  - CD40 promotion of amyloid beta production occurs via the NF-kappaB pathway.
AB  - The CD40 receptor is a member of the tumor necrosis factor (TNF) super-family of
      trans-membrane receptors. Interaction of CD40 with its ligand CD40L mediates a
      broad range of immune and inflammatory responses in the periphery and in the
      central nervous system. Recently it has been suggested that CD40/CD40L
      interaction is involved in amyloid precursor protein (APP) processing and
      Alzheimer's disease (AD)-like pathology in transgenic mouse models of AD. We have
      previously shown that pharmacologically inhibiting CD40/CD40L interaction
      improves memory deficits in the PSAPP AD mouse model. We have also recently shown
      that CD40 deficiency mitigates amyloid deposition in APPsw and PSAPP mouse
      models. In the present report, using human embryonic kidney cells (HEK293) over
      expressing both the APPsw mutation and CD40, we demonstrate that CD40/CD40L
      interaction directly increases the production of APP metabolites (Abeta 1-40,
      Abeta 1-42, CTFs, sAPPbeta and sAPPalpha). The results also show that CD40/CD40L
      interaction affects APP processing via the NF-kappaB pathway. Using NFkappaB
      inhibitors and SiRNAs to silence diverse elements of the NFkappaB pathway, we
      observe a reduction in levels of both Abeta 1-40 and Abeta 1-42. Taken together,
      our results further suggest that CD40L stimulation may be a key component in AD
      pathology and that elements of the NF-kappaB pathway may be suitable targets for
      therapeutic approaches against AD.

PMID- 17432960
TI  - Glial cell loss, proliferation and replacement in the contused murine spinal
      cord.
AB  - Studies in the rat have shown that contusive spinal cord injury (SCI) results in
      devastating pathology, including significant loss of mature oligodendrocytes and
      astrocytes even in spared white matter. Subsequently, there is increased
      proliferation of endogenous NG2(+) cells, postulated to contribute to replacement
      of mature glia chronically, which is important for functional recovery. Studies
      of mechanisms that stimulate endogenous progenitor cells would be facilitated by
      using mouse models with naturally occurring and genetically engineered mutations.
      To determine whether the murine response is similar to that in the rat, we
      performed contusive SCI on adult female C57Bl/6 mice at the T8-9 level. Animals
      received bromodeoxyuridine injections in the first week following injury and were
      killed at 1, 3, 4, 7 or 28 days postinjury (DPI). The overall loss of macroglia
      and the temporal-spatial response of NG2(+) cells after SCI in the (C57Bl/6)
      mouse was very similar to that in the (Sprague-Dawley) rat. By 24 h after SCI
      nearly half of the macroglia in spared ventral white matter had been lost. Cell
      proliferation was increased at 1-7 DPI, peaking at 3-4 DPI. Dividing cells
      included NG2(+) cells and Cd11b(+) macrophages and microglia. Furthermore, cells
      dividing in the first week expressed markers of mature glia at 28 DPI. The
      similarities in endogenous progenitor cell response to SCI in the mouse and rat
      suggest that this is a fundamental injury response, and that transgenic mouse
      models may be used to further probe how this cellular response to SCI might be
      enhanced to improve recovery after SCI.

PMID- 17432961
TI  - Age-related differences in the local cellular and molecular responses to injury
      in developing spinal cord of the opossum, Monodelphis domestica.
AB  - Immature spinal cord, unlike adult, has an ability to repair itself following
      injury. Evidence for regeneration, structural repair and development of
      substantially normal locomotor behaviour comes from studies of marsupials due to
      their immaturity at birth. We have compared morphological, cellular and molecular
      changes in spinal cords transected at postnatal day (P)7 or P14, from 3 h to 2
      weeks post-injury, in South American opossums (Monodelphis domestica). A bridge
      between severed ends of cords was apparent 5 days post-injury in P7 cords,
      compared to 2 weeks in P14. The volume of neurofilament (axonal) material in the
      bridge 2 weeks after injury was 30% of control in P7- but < 10% in P14-injured
      cords. Granulocytes accumulated at the site of injury earlier (3 h) in P7 than in
      P14 (24 h)-injured animals. Monocytes accumulated 24 h post-injury and
      accumulation was greater in P14 cords. Accumulation of GFAP-positive astrocytes
      at the lesion occurred earlier in P14-injured cords. Neurites and growth cones
      were identified ultrastructurally in contact with astrocytes forming the bridge.
      Results using mouse inflammatory gene arrays showed differences in levels of
      expression of many TGF, TNF, cytokine, chemokine and interleukin gene families.
      Most of the genes identified were up-regulated to a greater extent following
      injury at P7. Some changes were validated and quantified by RT-PCR. Overall, the
      results suggest that at least some of the greater ability to recover from spinal
      cord transection at P7 compared to P14 in opossums is due to differences in
      inflammatory cellular and molecular responses.

PMID- 17432962
TI  - Spinal cord injury-induced immune depression syndrome (SCI-IDS).
AB  - Infections are among the leading causes of death in spinal cord-injured patients,
      and are associated with hampered wound healing, prolonged hospitalization and
      impaired neurological recovery. We have analysed fluctuations of immune cell
      populations in an experimental rat model of spinal cord injury (SCI) by FACS
      analysis compared with sham-operated controls to detect the responses
      specifically induced by SCI. Further, to illustrate the impact of SCI only
      animals did not receive methylprednisolone in order to exclude confounding
      iatrogenic factors. Experimental SCI of rats induced a depletion of ED9(+)
      monocytes (< 45%, P < 0.01), CD3(+) T-lymphocytes (< 35%, P < 0.01), CD45 RA(+) B
      lymphocytes (< 25%, P < 0.01), MHC class II(+) (< 40%, P < 0.01) and OX-62(+)
      dendritic cells (< 50%, P = 0.032) within the first week after SCI. HIS 48(+)
      granulocytes remained on levels similar to sham-operated controls. Our data
      suggest that experimental SCI induces early onset of an immune suppression that
      we refer to as SCI-immune depression syndrome. Iatrogenic application of
      methylprednisolone in patients suffering may worsen the immune suppression. A
      deeper understanding of the underlying mechanisms of this novel syndrome might be
      essential to decrease mortality, costs (time of hospitalization) and to protect
      the intrinsic neurological recovery potential following SCI.

PMID- 17432963
TI  - Evidence from gene knockout studies implicates Asc-1 as the primary transporter
      mediating d-serine reuptake in the mouse CNS.
AB  - In the mammalian central nervous system, transporter-mediated reuptake may be
      critical for terminating the neurotransmitter action of D-serine at the
      strychnine insensitive glycine site of the NMDA receptor. The Na(+) independent
      amino acid transporter alanine-serine-cysteine transporter 1 (Asc-1) has been
      proposed to account for synaptosomal d-serine uptake by virtue of its high
      affinity for D-serine and widespread neuronal expression throughout the brain.
      Here, we sought to validate the contribution of Asc-1 to D-serine uptake in mouse
      brain synaptosomes using Asc-1 gene knockout (KO) mice. Total [(3)H]D-serine
      uptake in forebrain and cerebellar synaptosomes from Asc-1 knockout mice was
      reduced to 34 +/- 5% and 22 +/- 3% of that observed in wildtype (WT) mice,
      respectively. When the Na(+) dependent transport components were removed by
      omission of Na(+) ions in the assay buffer, D-serine uptake in knockout mice was
      reduced to 8 +/- 1% and 3 +/- 1% of that measured in wildtype mice in forebrain
      and cerebellum, respectively, suggesting Asc-1 plays a major role in the Na(+)
      independent transport of D-serine. Potency determination of D-serine uptake
      showed that Asc-1 mediated rapid high affinity Na(+) independent uptake with an
      IC(50) of 19 +/- 1 microm. The remaining uptake was mediated predominantly via a
      low affinity Na(+) dependent transporter with an IC(50) of 670 +/- 300 microm
      that we propose is the glial alanine-serine-cysteine transporter 2 (ASCT2)
      transporter. The results presented reveal that Asc-1 is the only high affinity D
      serine transporter in the mouse CNS and is the predominant mechanism for D-serine
      reuptake.

PMID- 17432964
TI  - Development of non-phosphorylated neurofilament protein expression in neurones of
      the New World monkey dorsolateral frontal cortex.
AB  - We studied developmental changes in the expression of non-phosphorylated
      neurofilament protein (NNF) (a marker of the structural maturation of pyramidal
      neurones) in the dorsolateral frontal cortex of marmoset monkeys, between
      embryonic day 130 and adulthood. Our focus was on cortical fields that send
      strong projections to extrastriate cortex, including the dorsal and ventral
      subdivisions of area 8A, area 46 and area 6d. For comparison, we also
      investigated the maturation of prefrontal area 9, which has few or no connections
      with visual areas. The timing of expression of NNF immunostaining in early life
      can be described as the result of the interaction of two developmental gradients.
      First, there is an anteroposterior gradient of maturation in the frontal lobe,
      whereby neurones in caudal areas express NNF earlier than those in rostral areas.
      Second, there is a laminar gradient, whereby the first NNF-immunoreactive
      neurones emerge in layer V, followed by those in progressively more superficial
      parts of layer III. Following a peak in density of NNF-immunopositive cell
      numbers in layer V at 2-3 months of age, there is a gradual decline towards
      adulthood. In contrast, the density of immunopositive cells in layer III
      continues to increase throughout the first postnatal year in area 6d and until
      late adolescence (> 1.5 years of age) in prefrontal areas. The present results
      support the view that the maturation of visual cognitive functions involves
      relatively late processes linked to structural changes in frontal cortical areas.

PMID- 17432965
TI  - Spatial and temporal frequency selectivity of neurons in the middle temporal
      visual area of new world monkeys (Callithrix jacchus).
AB  - Information about the responses of neurons to the spatial and temporal
      frequencies of visual stimuli is important for understanding the types of
      computations being performed in different visual areas. We characterized the
      spatiotemporal selectivity of neurons in the middle temporal area (MT), which is
      deemed central for the processing of direction and speed of motion. Recordings
      obtained in marmoset monkeys using high-contrast sine-wave gratings as stimuli
      revealed that the majority of neurons had bandpass spatial and temporal frequency
      tuning, and that the selectivity for these parameters was largely separable. Only
      in about one-third of the cells was inseparable spatiotemporal tuning detected,
      this typically being in the form of an increase in the optimal temporal frequency
      as a function of increasing grating spatial frequency. However, most of these
      interactions were weak, and only 10% of neurons showed spatial frequency
      invariant representation of speed. Cells with inseparable spatiotemporal tuning
      were most commonly found in the infragranular layers, raising the possibility
      that they form part of the feedback from MT to caudal visual areas. While spatial
      frequency tuning curves were approximately scale-invariant on a logarithmic
      scale, temporal frequency tuning curves covering different portions of the
      spectrum showed marked and systematic changes. Thus, MT neurons can be reasonably
      described as similarly built spatial frequency filters, each covering a different
      dynamic range. The small proportion of speed-tuned neurons, together with the
      laminar position of these units, are compatible with the idea that an explicit
      neural representation of speed emerges from computations performed in MT.

PMID- 17432966
TI  - Cholinergic modulation incorporated with a tone presentation induces frequency
      specific threshold decreases in the auditory cortex of the mouse.
AB  - Learning-induced or experience-dependent auditory cortical plasticity has often
      been characterized by frequency-specificity. Studies have revealed the critical
      role of the cholinergic basal forebrain and acoustic guidance. Cholinergic
      facilitation of specific thalamocortical inputs potentially determines such
      frequency-specificity but this issue requires further clarification. To examine
      the cholinergic effects on thalamocortical circuitry of specific frequency
      channels, we recorded the responses of cortical neurons while pairing basal
      forebrain activation or acetylcholine (ACh) microiontophoresis with tone
      presentations at 10 dB below the neuronal response threshold. We found that both
      basal forebrain activation and acetylcholine microiontophoresis paired with a
      tone induced a significant decrease in response threshold of the recorded
      cortical neurons to the frequency of the paired tone, and that this threshold
      decrease could be eliminated by atropine microiontophoresis. Our data suggest
      that cortical acetylcholine specifically facilitates thalamocortical circuitry
      tuned to the frequency of a presented tone; it is the first, fundamental step
      towards frequency-specific cortical plasticity evoked by auditory learning and
      experience.

PMID- 17432967
TI  - Chronic intracerebral prolactin attenuates neuronal stress circuitries in virgin
      rats.
AB  - Prolactin (PRL) has been shown to promote maternal behaviour, and to regulate
      neuroendocrine and emotional stress responses. These effects appear more
      important in the peripartum period, when the brain PRL system is highly
      activated. Here, we studied the mechanisms that underlie the anti-stress effects
      of PRL. Ovariectomized, estradiol-substituted Wistar rats were implanted with an
      intracerebroventricular cannula and treated with ovine PRL (0.01, 0.1 or 1
      microg/h; 5 days via osmotic minipumps) or vehicle, and their responses to acute
      restraint stress was assessed. Chronic PRL treatment exerted an anxiolytic effect
      on the elevated plus-maze, and attenuated the acute restraint-induced rise in
      plasma adrenocorticotropin, corticosterone and noradrenaline. At the neuronal
      level, in situ hybridization revealed PRL effects on the expression patterns of
      the immediate-early gene c-fos and corticotropin-releasing factor (CRF). Under
      basal conditions, PRL significantly reduced c-fos mRNA expression within the
      central amygdala. In response to restraint, the expression of both c-fos mRNA and
      protein and of CRF mRNA was decreased in the parvocellular part of the
      paraventricular nucleus (PVN) of PRL-treated compared with vehicle-treated
      animals. In conclusion, our data demonstrate that chronic elevation of PRL levels
      within the brain results in reduced neuronal activation within the hypothalamus,
      specifically within the PVN, in response to an acute stressor. Thus, PRL acting
      at various relevant brain regions exerts profound anxiolytic and anti-stress
      effects, and is likely to contribute to the attenuated stress responsiveness
      found in the peripartum period, when brain PRL levels are physiologically
      upregulated.

PMID- 17432968
TI  - Maintenance of superior learning and memory function in NR2B transgenic mice
      during ageing.
AB  - Brain ageing represents a general and evolutionarily conserved phenomenon and is
      marked by gradual declines in cognitive functions such as learning and memory. As
      a synaptic coincidence detector, the N-methyl-d-aspartate (NMDA) receptor is
      known to be essential for the induction of synaptic plasticity and memory
      formation. Here, we test the hypothesis that up-regulation of NR2B expression is
      beneficial for learning and memory in the aged animals. Our in vitro recordings
      show that the aged transgenic mice with the forebrain-specific overexpression of
      the NR2B subunit indeed exhibit more robust hippocampal long-term potentiation
      (LTP) induced by either high-frequency stimulation or theta-stimulation protocol.
      Furthermore, those aged NR2B transgenic mice consistently outperform their wild
      type littermates in five different learning and memory tests, namely, novel
      object recognition, contextual and cued fear conditioning, spatial reference
      memory, and spatial working memory T-maze task. Thus, we conclude that increased
      expression of NR2B in the forebrain improves learning and memory function in the
      aged brain.

PMID- 17432969
TI  - Forebrain mineralocorticoid receptor overexpression enhances memory, reduces
      anxiety and attenuates neuronal loss in cerebral ischaemia.
AB  - The nuclear mineralocorticoid receptor (MR), a high-affinity receptor for
      glucocorticoids, is highly expressed in the hippocampus where it underpins
      cognitive, behavioural and neuroendocrine regulation. Increased neuronal MR
      expression occurs early in the response to cellular injury in vivo and in vitro
      and is associated with enhanced neuronal survival. To determine whether increased
      neuronal MR might be causal in protecting against ischaemic damage in vivo we
      generated a forebrain-specific MR-overexpressing transgenic mouse (MR-Tg) under
      the control of the CamKII alpha promoter, and subjected mice to transient
      cerebral global ischaemia induced by bilateral common carotid artery occlusion
      for 20 min. We also separately assessed the effects of MR overexpression on
      hypothalamic-pituitary-adrenal (HPA) axis activity and cognitive and affective
      functions in noninjured animals. Our results showed that MR-Tg mice had
      significantly reduced neuronal death following transient cerebral global
      ischaemia compared to wild-type littermates. This effect was not associated with
      alterations in basal or poststress HPA axis function or in arterial blood
      pressure. MR-Tg mice also demonstrated improved spatial memory retention, reduced
      anxiety and altered behavioural response to novelty. The induction of neuronal MR
      appears to offer a protective response which has potential therapeutic
      implications in cerebral ischaemia and cognitive and affective disorders.

PMID- 17432970
TI  - Molecular markers distinguishing supragranular and infragranular layers in the
      human prefrontal cortex.
AB  - The human neocortex is organized into six layers that are differentiated by the
      size and packing density of their constituent neurons. The gene products that
      guide the establishment of this lamination have been studied extensively, but the
      gene expression gradients present across the layers of the adult human neocortex
      are mostly unknown. As the supragranular (SG) and infragranular (IG) layers of
      the human prefrontal cortex (PFC) differ in their connectivity and developmental
      time course, we hypothesized that the SG and IG layers will show distinct
      differences in their transcriptomes. To test this prediction, we used laser
      capture microdissection coupled with DNA microarray transcriptome profiling.
      Sixty-nine genes exhibited robust and highly consistent expression differences
      between the SG and IG layers. For six selected markers, in addition to validating
      the microarray findings, in situ hybridization revealed a complex, subpopulation
      specific neuronal distribution. The markers we identified are likely to be
      related to the functional differences between the SG and IG layers of the human
      PFC and can be used for assessing alterations in structure and function of this
      cortical region in human brain disorders.

PMID- 17432971
TI  - Umami: a delicious flavor formed by convergence of taste and olfactory pathways
      in the human brain.
AB  - Umami taste is produced by glutamate acting on a fifth taste system. However,
      glutamate presented alone as a taste stimulus is not highly pleasant, and does
      not act synergistically with other tastes (sweet, salt, bitter and sour). We show
      here that when glutamate is given in combination with a consonant, savory, odour
      (vegetable), the resulting flavor can be much more pleasant. Moreover, we showed
      using functional brain imaging with fMRI that the glutamate taste and savory
      odour combination produced much greater activation of the medial orbitofrontal
      cortex and pregenual cingulate cortex than the sum of the activations by the
      taste and olfactory components presented separately. Supralinear effects were
      much less (and significantly less) evident for sodium chloride and vegetable
      odour. Further, activations in these brain regions were correlated with the
      pleasantness and fullness of the flavor, and with the consonance of the taste and
      olfactory components. Supralinear effects of glutamate taste and savory odour
      were not found in the insular primary taste cortex. We thus propose that
      glutamate acts by the nonlinear effects it can produce when combined with a
      consonant odour in multimodal cortical taste-olfactory convergence regions. We
      propose the concept that umami can be thought of as a rich and delicious flavor
      that is produced by a combination of glutamate taste and a consonant savory
      odour. Glutamate is thus a flavor enhancer because of the way that it can combine
      supralinearly with consonant odours in cortical areas where the taste and
      olfactory pathways converge far beyond the receptors.

PMID- 17432972
TI  - The relationship between brain activity and peak grip force is modulated by
      corticospinal system integrity after subcortical stroke.
AB  - In healthy human subjects, the relative contribution of cortical regions to motor
      performance varies with the task parameters. Additionally, after stroke,
      recruitment of cortical areas during a simple motor task varies with
      corticospinal system integrity. We investigated whether the pattern of motor
      system recruitment in a task involving increasingly forceful hand grips is
      influenced by the degree of corticospinal system damage. Nine chronic subcortical
      stroke patients and nine age-matched controls underwent functional magnetic brain
      imaging whilst performing repetitive isometric hand grips. Target grip forces
      were varied between 15% and 45% of individual maximum grip force. Corticospinal
      system functional integrity was assessed with transcranial magnetic stimulation.
      Averaged across all forces, there was more task-related activation compared with
      rest in the secondary motor areas of patients with greater corticospinal system
      damage, confirming previous reports. However, here we were primarily interested
      in regional brain activation, which covaried with the amount of force generated,
      implying a prominent executive role in force production. We found that in control
      subjects and patients with lesser corticospinal system damage, signal change
      increased linearly with increasing force output in contralateral primary motor
      cortex, supplementary motor area and ipsilateral cerebellum. In contrast, in
      patients with greater corticospinal system damage, force-related signal changes
      were seen mainly in contralesional dorsolateral premotor cortex, bilateral
      ventrolateral premotor cortices and contralesional cerebellum, but not
      ipsilesional primary motor cortex. These findings suggest that the premotor
      cortices might play a new and functionally relevant role in controlling force
      production in patients with more severe corticospinal system disruption.

PMID- 17432973
TI  - Search for fMRI BOLD signals in networks of spiking neurons.
AB  - In a recent experiment, functional magnetic resonance imaging blood oxygen level
      dependent (fMRI BOLD) signals were compared in different cortical areas (primary
      visual and associative), when subjects were required covertly to name images in
      two protocols: sequences of images, with and without intervening delays. The
      amplitude of the BOLD signal in protocols with delay was found to be closer to
      that without delays in associative areas than in primary areas. The present study
      provides an exploratory proposal for the identification of the neural activity
      substrate of the BOLD signal in quasi-realistic networks of spiking neurons, in
      networks sustaining selective delay activity (associative) and in networks
      responsive to stimuli, but whose unique stationary state is one of spontaneous
      activity (primary). A variety of observables are 'recorded' in the network
      simulations, applying the experimental stimulation protocol. The ratios of the
      candidate BOLD signals, in the two protocols, are compared in networks with and
      without delay activity. There are several options for recovering the experimental
      result in the model networks. One common conclusion is that the distinguishing
      factor is the presence of delay activity. The effect of NMDAr is marginal. The
      ultimate quantitative agreement with the experiment results depends on a
      distinction of the baseline signal level from its value in delay-period
      spontaneous activity. This may be attributable to the subjects' attention.
      Modifying the baseline results in a quantitative agreement for the ratios, and
      provided a definite choice of the candidate signals. The proposed framework
      produces predictions for the BOLD signal in fMRI experiments, upon modification
      of the protocol presentation rate and the form of the response function.

PMID- 17432974
TI  - Inhibitory effect of voluntary movement preparation on cutaneous heat pain and
      laser-evoked potentials.
AB  - In our study, preparation of voluntary movement was used to physiologically
      activate the motor cortex areas and the effect of this activation on CO(2) laser
      evoked potentials (LEPs) was explored. LEPs were recorded from 31 scalp
      electrodes in 10 healthy subjects after painful stimulation of the right C6-C7
      skin dermatomes. LEP stimuli were delivered in the time interval between a visual
      warning stimulus followed after 1 s. by an imperative stimulus. The imperative
      stimulus triggered: (i) no task in the baseline condition (Pain); (ii) flexion
      extension movements of the second finger of the right hand in the movement
      condition (Pain + Movement); (iii) cognitive task (mathematic computation) in the
      distraction condition (Pain + Cognition). The experimental conditions were also
      repeated during application of laser stimuli on the left C6-C7 skin dermatomes.
      Compared with the baseline condition (no task required), during preparation of
      right-hand voluntary movement there was a significant reduction in LEP amplitude
      and subjective pain rating after right- but not after left-hand stimulation,
      which suggests that the observed effect cannot be attributed to a nonspecific
      reduction in attention toward painful stimulus. During preparation of a cognitive
      task, LEP amplitude was reduced compared to baseline. Our results represent the
      first neurophysiological suggestion that physiological activation of the motor
      cortex, occurring during movement preparation, inhibits cortical pain processing
      by a centrifugal mechanism.

PMID- 17432975
TI  - Mobile phone emission modulates interhemispheric functional coupling of EEG alpha
      rhythms.
AB  - We tested the working hypothesis that electromagnetic fields from mobile phones
      (EMFs) affect interhemispheric synchronization of cerebral rhythms, an important
      physiological feature of information transfer into the brain. Ten subjects
      underwent two electroencephalographic (EEG) recordings, separated by 1 week,
      following a crossover double-blind paradigm in which they were exposed to a
      mobile phone signal (global system for mobile communications; GSM). The mobile
      phone was held on the left side of the subject head by a modified helmet, and
      orientated in the normal position for use over the ear. The microphone was
      orientated towards the corner of the mouth, and the antenna was near the head in
      the parietotemporal area. In addition, we positioned another similar phone (but
      without battery) on the right side of the helmet, to balance the weight and to
      prevent the subject localizing the side of GSM stimulation (and consequently
      lateralizing attention). In one session the exposure was real (GSM) while in the
      other it was Sham; both sessions lasted 45 min. Functional interhemispheric
      connectivity was modelled using the analysis of EEG spectral coherence between
      frontal, central and parietal electrode pairs. Individual EEG rhythms of interest
      were delta (about 2-4 Hz), theta (about 4-6 Hz), alpha 1 (about 6-8 Hz), alpha 2
      (about 8-10 Hz) and alpha 3 (about 10-12 Hz). Results showed that, compared to
      Sham stimulation, GSM stimulation modulated the interhemispheric frontal and
      temporal coherence at alpha 2 and alpha 3 bands. The present results suggest that
      prolonged mobile phone emission affects not only the cortical activity but also
      the spread of neural synchronization conveyed by interhemispherical functional
      coupling of EEG rhythms.

PMID- 17432976
TI  - Treatment with IFNalpha in vivo up-regulates serum-soluble TNF-related apoptosis
      inducing ligand (sTRAIL) levels and TRAIL mRNA expressions in neutrophils in
      chronic myelogenous leukemia patients.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an interferon
      alpha (IFNalpha)-induced, apoptosis-inducing molecule. TRAIL could be one of the
      reagents for therapeutic use in combination with imatinib in chronic myeloid
      leukemia (CML). Here we examined serum-soluble TRAIL (sTRAIL) levels in CML
      patients either before or during therapies with IFNalpha or imatinib. In
      untreated CML patients, serum sTRAIL was detectable and the levels were
      substantially comparable with those in healthy donors. sTRAIL levels
      significantly increased in patients during IFNalpha therapy, but not at all in
      patients during imatinib therapy. TRAIL mRNA expressions in neutrophils in CML
      patients undergoing IFNalpha therapy was significantly elevated when compared
      with those in patients prior to therapy. TRAIL mRNA expressions were also
      detectable in CD34-positive cells in bone marrow, and the levels increased in
      patients during IFNalpha therapy. In vitro IFNalpha stimulation of CML
      neutrophils increased intracellular TRAIL rather than cell-surface TRAIL, and the
      secretion of sTRAIL in the culture supernatant was observed. This sTRAIL
      secretion was augmented with lipopolysaccharide (LPS) stimulation only in
      IFNalpha-primed neutrophils, whereas LPS alone had no effect. Taken together, in
      vivo IFNalpha treatment provokes the release of sTRAIL when administered
      systematically in CML patients. The main source of the IFNalpha-induced serum
      sTRAIL may be neutrophils in CML, and sTRAIL may be one of the mechanisms of the
      anti-proliferative action of IFNalpha on CML. These findings give another
      rationale for the use of IFNalpha or recombinant sTRAIL in CML, and also
      implicate the potential importance of neutrophils in tumor immunosurveillance.

PMID- 17432977
TI  - Establishment and characterization of a novel imatinib-sensitive chronic myeloid
      leukemia cell line MYL, and an imatinib-resistant subline MYL-R showing
      overexpression of Lyn.
AB  - In chronic myeloid leukemia (CML), resistance to imatinib is diverse. In addition
      to BCR-ABL-dependent mechanisms, BCR-ABL-independent mechanisms have been
      proposed. Here we established and characterized novel CML cell lines, an imatinib
      sensitive cell line, MYL, and an imatinib-resistant subline, MYL-R. Treatment
      with imatinib inhibited phosphorylation of BCR-ABL and CrkL in both MYL and MYL
      R, even though imatinib-induced apoptosis was preferentially observed in MYL than
      MYL-R, indicating that the resistance is based on a BCR-ABL-independent
      mechanism. MYL-R showed elevated expressions of Lyn mRNA, Lyn protein,
      phosphorylated Lyn, and phosphorylated STAT5. Silencing of Lyn by short
      interfering RNA (siRNA) in MYL-R, but not in MYL, induced significant growth
      inhibition, increased caspase-3 activity, and induced partial recovery from
      imatinib-resistance. Expression of Bcl-2, previously reported to be associated
      with Lyn-mediated resistance, was not elevated in MYL-R. Expression of Bim, which
      plays an important role in imatinib-induced cell-killing, was not suppressed in
      MYL-R. These results imply that diverse mechanisms of resistance exist among cell
      types. Treatment of MYL-R cells with various reagents known to have anti-leukemic
      activity revealed that zoledronic acid and the farnesyl transferase inhibitor
      (SCH 66336) showed strong synergism with imatinib; interferon alpha, PP2,
      CGP76030, and FK228 (depsipeptide) showed synergism; whereas soluble TRAIL and
      As2O3 showed additivity or antagonism, and 17-AAG and radicicol showed
      antagonism. Treatment with either PP2 or zoledronic acid induced greater growth
      reduction in MYL-R than MYL. Taken together, Lyn may play an important role in
      imatinib-resistance in MYL-R. Some novel reagents, including siRNA targeting Lyn,
      may have good potential to overcome this resistance.

PMID- 17432978
TI  - From science to daily practice.

PMID- 17432979
TI  - Accurate staging, selective preoperative therapy and optimal surgery improves
      outcome in rectal cancer: a review of the recent evidence.
AB  - OBJECTIVE: The current optimal management of locally advanced rectal cancer has
      evolved from surgical excision followed by postoperative therapy in patients with
      involved margins, to an increasing use of a preoperative strategy to 'down-stage
      and/or down-size' the tumour. This treatment strategy is based on the
      relationship of the tumour to the mesorectal fascia, the optimal surgical
      circumferential resection margin that can be achieved by total mesorectal
      excision. We have reviewed the recent evidence for this strategy. METHOD: An
      electronic literature search using PubMed identified articles on the subject of
      rectal cancer between January 2000 and December 2005. The search was limited to
      English language publications with secondary references obtained from key
      articles. Articles published in high impact factor journals formed the basis of
      the review, together with articles related to national programmes on the
      management of rectal cancer. This does lead to a selection bias, particularly as
      the articles identified had a European bias. CONCLUSION: The UK NHS Cancer Plan
      has outlined the basis for the multidisciplinary team (MDT) management of rectal
      cancer. Advances in preoperative assessment through accurate staging and the
      recognition of the importance of the relationship of the tumour to the mesorectal
      fascia has allowed the selection of patients for a preoperative strategy to down
      size/down-stage the tumour if this fascial layer is involved or threatened.
      Improvements in the quality of surgical resection through the acceptance of the
      principle of total mesorectal excision have ensured that optimal surgery remains
      the cornerstone to successful treatment. Further refinements of the MDT process
      strive to improve outcome. Accurate radiological staging, optimal surgery and
      detailed histopathological assessment together with consideration of a
      preoperative neoadjuvant strategy should now form the basis for current treatment
      and future research in rectal cancer.

PMID- 17432980
TI  - Saving the sphincter in rectal cancer: are we prepared to change practice?
AB  - Total mesorectal excision and preoperative radiation with or without chemotherapy
      has led to a reduction in local recurrence rates in patients with rectal cancer.
      This article examines the effect such treatment has on the rate of sphincter
      preservation in patients with rectal cancers close to the anal sphincter
      mechanism and looks at the evidence for changing clinical practice.

PMID- 17432982
TI  - Meta-analysis of short-term and long-term outcomes of J, W and S ileal reservoirs
      for restorative proctocolectomy.
AB  - OBJECTIVE: The choice of ileal pouch reservoir has been a contentious subject
      with no consensus as to which technique provides better function. This study
      aimed to compare short- and long-term outcomes of three ileal reservoir designs.
      METHOD: Comparative studies published between 1985 and 2000 of J, W and S ileal
      pouch reservoirs were included. Meta-analytical techniques were employed to
      compare postoperative complications, pouch failure, and functional and
      physiological outcomes. Quality of life following surgery was also assessed.
      RESULTS: Eighteen studies, comprising 1519 patients (689 J pouch, 306 W pouch and
      524 S pouch) were included. There was no significant difference in the incidence
      of early postoperative complications between the three groups. The frequency of
      defecation over 24 h favoured the use of either a W or S pouch [J vs S: weighted
      mean difference (WMD) 1.48, P < 0.001; J vs W: WMD 0.97, P = 0.01]. The S pouch
      was associated with an increased need for pouch intubation (S vs J: OR 6.19, P =
      0.04). The use of a J pouch was associated with a significantly higher prevalence
      of use of anti-diarrhoeal medication (J vs S: OR 2.80, P = 0.01; J vs W: OR 3.55,
      P < 0.001). CONCLUSION: All three reservoirs had similar perioperative
      complication rates. The S pouch was associated with the need for anal intubation.
      There was less frequency and less need for antidiarrhoeal agents with the W
      rather than the J pouch.

PMID- 17432983
TI  - Long-term cancer risk of the anorectal cuff following restorative proctocolectomy
      assessed by p53 expression and cuff dysplasia.
AB  - OBJECTIVE: Restorative proctocolectomy (RP) for ulcerative colitis (UC) retains a
      'cuff' of columnar rectal epithelium that has unknown risk of malignant change.
      Markers of malignant potential in UC include aberrant p53 expression and
      dysplasia. We undertook a prospective study comprising serial surveillance biopsy
      and assessed the occurrence of aberrant p53 expression, epithelial dysplasia and
      carcinoma in the retained anorectal cuff following stapled RP. METHOD: A total of
      110 patients who underwent stapled RP for UC between 1988 and 1998 were followed
      up by cuff surveillance biopsies under general anaesthesia. Histological samples
      were analysed by a specialist colorectal pathologist for the presence of rectal
      mucosa, dysplasia and carcinoma. Immunohistochemistry for p53 expression was
      performed for each most recent cuff biopsy. Median follow-up was 56 months (12
      145) and median time since diagnosis of UC was 8.8 years (2-32). RESULTS: Rectal
      mucosa was obtained from the cuff in 65% of biopsies. No overt carcinomas
      developed during the follow-up period and there was no dysplasia or carcinoma in
      any cuff biopsy. The p53 overexpression was identified in 38 specimens (50.6%),
      but was also identified in controls (3/3 colitis, 3/3 ileal pouch and 6/6 stapled
      haemorrhoidectomy donuts). CONCLUSION: The lack of carcinoma and dysplasia in the
      columnar cuff epithelium specimens is reassuring. The lack of stabilized p53 and
      absence of a relationship between p53 stabilization and dysplasia up to 12 years
      after pouch formation suggests neoplastic transformation is a rare event.
      Furthermore, p53 expression was not useful in surveillance of cuff biopsies from
      patients who have undergone RP for UC and the search should continue for
      alternative predysplastic markers. These data suggest that in patients who do not
      have high-grade dysplasia or colorectal cancer at the time of RP, cuff
      surveillance in the first decade after pouch formation is unnecessary. However,
      we consider regular cuff surveillance biopsies should continue for patients with
      high-grade dysplasia, whether or not there was a carcinoma in the original
      colectomy specimen.

PMID- 17432984
TI  - Recto-urethral fistula following brachytherapy for localized prostate cancer.
AB  - OBJECTIVE: The use of prostate brachytherapy (BT) in the management of prostate
      cancer is increasing. BT is often chosen because of its perceived lower toxicity
      when compared with other radical therapy options. Rarely however serious
      complications can occur. One such complication is recto-urethral fistula (RUF).
      We report the incidence of RUF following BT at our centre and review the
      potential factors in fistula development. METHOD: A prospectively collected
      database was used to identify cases of RUF among 1455 patients treated with
      prostate BT at a single UK centre with at least 2 years of follow up. This
      included patients treated with BT monotherapy, as well as those treated with BT
      combined with external beam radiotherapy and BT used as salvage as all these
      groups have a higher incidence of RUF. Implant dose and volume characteristics
      for those patients, their co-morbidities and history of endoscopic procedures
      were recorded. RESULTS: Recto-urethral fistula was identified in three (0.2%)
      patients, occurring at 19-27 months following BT. All these patients had BT
      monotherapy. All three patients had rectal symptoms after their BT and had been
      investigated with endoscopy and low rectal biopsy. Subsequent surgical management
      with faecal and/or urinary diversion was required. On review of patients' BT
      details, radiation dose and volume parameters were higher on the postprocedure CT
      calculations than had been suggested by the preimplant plan. No other
      predisposing risk factors for RUF were identified. CONCLUSION: The incidence of
      RUF in our population is low. RUF following BT has been associated with rectal
      biopsy in previous series and this is confirmed in our report. Gastrointestinal
      specialists should not perform biopsy of the anterior rectum in patients who have
      had BT unless there is a very high clinical suspicion of malignancy.

PMID- 17432985
TI  - Early results of immediate repair of obstetric third-degree tears: 65% are
      completely asymptomatic despite persistent sphincter defects in 61%.
AB  - OBJECTIVE: The outcome of immediate repair of obstetric third-degree tears is
      poorly documented. Immediate repair may give better functional results than
      delayed repair because scarring is reduced. This aim of this prospective study
      was to examine the early outcome of immediate repair of third-degree tears.
      METHOD: A total of 121 women who had immediate repair of obstetric third-degree
      tears underwent interview, anal ultrasonography and anorectal physiology.
      RESULTS: At review, 79 (65%) were completely asymptomatic (score = 0), 23 (19%),
      had minor flatus incontinence or mild urgency causing no compromise to their
      quality of life (score 1-4), and 19 (16%) had clinically embarrassing faecal
      incontinence (score 5-24). Thirty-nine (32%) had an intact internal anal
      sphincter (IAS) and external anal sphincter (EAS) (i.e. a successful repair),
      eight (7%) had a defect in the IAS alone but the EAS was intact (i.e. a
      successful repair but a residual IAS defect), 43 (35%) had a residual defect in
      the EAS alone (IAS intact) and 31 (26%) had a persistent defect in the IAS and
      EAS. Residual defects in either or both of the sphincters were associated with a
      significantly higher incidence of abnormal resting and squeeze anal pressures.
      Anal manometry had no correlation with symptoms. The highest proportion of severe
      incontinence was in those with an IAS defect alone (37%) and when there was a
      residual IAS and EAS defect (24%). Only 2 of 39 (5%) with an intact IAS and EAS
      had severe incontinence and only 8 of 43 (18%) with a residual EAS defect alone
      had severe faecal incontinence. CONCLUSION: These results indicate a good outcome
      following immediate repair of third-degree obstetric tears and emphasize the role
      of the IAS in providing continence.

PMID- 17432986
TI  - Evaluating the accuracy of data entry in a regional colorectal cancer database:
      implications for national audit.
AB  - OBJECTIVE: To determine the accuracy and completeness of data entry in a regional
      colorectal cancer database. METHOD: Records were obtained for 50 patients
      selected at random from the database. A sample of 18 key data points
      (preoperative and operative) were selected from the Association of Coloproctology
      of Great Britain and Ireland colorectal cancer minimum dataset. Data were
      extracted from the case notes by a clinician and compared with database entries.
      RESULTS: Overall 83% of data elements were present in the patient records. There
      was agreement between patient records and the database for 61% of data points
      overall, and for 70% of preoperative data and 47% of operative data. CONCLUSION:
      The regional colorectal cancer database is inaccurate, particularly regarding
      operative data. Insufficient information in patient records accounts for a
      proportion of missing data, and lack of agreement between records and the
      database may be due to misinterpretation of records by nonclinical staff. The
      accuracy of regional data may be improved by weekly review of database entries
      and/or entry of clinical data by a clinician.

PMID- 17432987
TI  - Outcomes in 2748 patients referred to a colorectal two-week rule clinic.
AB  - OBJECTIVE: To assess the 3-year outcomes of a nurse-led, one-stop, 2-week rule
      (TWR) clinic for suspected colorectal cancer (CRC) in a large teaching hospital.
      METHOD: Data were collected prospectively from January 2002 to December 2004. In
      total, 2748 patients were seen over the 3-year period. The ratio of male:female
      subjects was 1190:1558 (43%:57%). Median age at presentation was 66 years (range
      17-96). RESULTS: A total of 1363 (49.6%) nonconforming referrals were made; 1300
      patients (47.3%) underwent flexible sigmoidoscopy during their initial assessment
      in clinic; 1439 patients (52.4%) underwent a barium enema during the course of
      their investigation; 2503 patients (91.1%) were seen within 14 working days. The
      median overall wait for the initial clinic appointment was 10 days. The annual
      number of patients seen was similar over the 3-year period. A total of 174
      cancers (6.3%) were identified which accounted for 36.4% of all CRCs diagnosed
      during the study period. Nineteen cancers presented in the nonconforming group
      (1.6% of all non-conforming patients). Rectal tumours accounted for 59.8% (n =
      104) of all cancers diagnosed while right-sided tumours accounted for only 10.9%
      (n = 19). Advanced tumours accounted for 73.0% (n = 127) of the total; 133
      (76.4%) cancer patients underwent some form of surgical intervention. CONCLUSION:
      A specialist nurse-led, one-stop TWR clinic for suspected colorectal cancer is
      sustainable and can be run successfully with over 90% of referrals seen within
      the targeted time period. The proportion of non-conforming referrals was high and
      a large number of advanced and unstaged tumours was observed. Low numbers of
      proximal tumours were detected.

PMID- 17432988
TI  - Segmental colonic transit studies: comparison of a radiological and a
      scintigraphic method.
AB  - OBJECTIVE: Colonic transit studies are used to diagnose slow transit constipation
      (STC) and to evaluate segmental colonic transit before segmental or subtotal
      colectomy. The aim of the study was to compare a single X-ray radio-opaque marker
      method with a scintigraphic technique to assess total and segmental colonic
      transit in patients with STC. METHOD: Thirty-one female patients (median age 46
      years) with severe constipation and a prolonged or borderline prolonged colonic
      transit time on radio-opaque marker study were included in the study. They were
      subsequently investigated with (111)Indium-DTPA colonic transit scintigraphy,
      with a median time between the investigations of 4(range 1-27) months. Normal
      values of healthy female controls were used for comparison. RESULTS: There was no
      difference between the two methods in terms of prolonged or normal total colonic
      transit time. Twenty-nine of 31 female patients had a prolonged transit time only
      in one or two segments on the marker study. On scintigraphy, the transit time was
      prolonged for patients in the left (P < 0.05 to P < 0.001), but not in the right
      colon. With respect to prolonged or normal segmental transit time, there was a
      significant difference between the two methods only in the descending colon (P =
      0.02). However, the results varied considerably for individual patients.
      CONCLUSION: Segmental colonic delay was a common finding. The two methods gave
      similar results for groups of patients, except in the descending colon. The
      variation of the results for individuals suggests that a repeated transit test
      may improve the assessment of total and segmental transit.

PMID- 17432989
TI  - A prospective evaluation of stapled haemorrhoidopexy/rectal mucosectomy in the
      management of 3rd and 4th degree haemorrhoids.
AB  - OBJECTIVE: We have audited our 5 years experience of circumferential-stapled
      haemorrhoidopexy (PPH). METHOD: A prospectively collected electronic data base of
      our 5-year experience to September 2005 has been examined. RESULTS: A total of
      357 consecutive patients (220 - 62% women, median age 46 years; range 28-92) with
      symptomatic third- and fourth-degree haemorrhoids (ratio 222:135) have undergone
      a stapled haemorrhoidopexy/rectal mucosectomy. One hundred and thirty-two (37%)
      had failed previous banding; 42 (12%) had undergone a Milligan-Morgan
      haemorrhoidectomy in the past. All but one was performed under general
      anaesthetic. Mean duration of surgery was 15 min (range 11-40); 299 (84%) were
      planned day cases (three patients were admitted overnight for pain relief (2) and
      retention of urine) and 57 were planned successful overnight stays. Reactive
      postoperative bleeding requiring a blood transfusion occurred in three patients
      (0.8%): one returned to theatre (0.2%). Three patients (0.8%) had a secondary
      haemorrhage requiring a hospital visit, one was admitted overnight. Four patients
      complaining of severe pain were managed in the community. Transient urgency was
      reported in 92 patients (26%); 58 (63%) were men, faecal impaction 4 (1.1%),
      minor staple line stenosis requiring dilatation 5 (1.4%), peri-anal sepsis from
      an associated untreated chronic anal fissure 1 (0.2%). Normal work was resumed
      between 3 and 31 days (median 7). Five patients re-presented with recurrent
      symptoms between 14 & 18 months: further treatment comprised a repeat PPH in
      three (one was very painful), banding 1 and reassurance alone. A further patient
      re-presented with minor soiling which responded to physiotherapy. CONCLUSION:
      Stapled haemorrhoidopexy/rectal mucosectomy is a safe, effective and predictable
      treatment of third- and fourth- degree haemorrhoids and in the majority of
      patients can be carried out on a day case basis.

PMID- 17432990
TI  - Long-term results of perianal silicone injection for faecal incontinence.
AB  - OBJECTIVE: Perianal injection of bulking agents is a simple method for treating
      passive faecal incontinence. To date only short-term results of treatment are
      available. This study is the first to determine the efficacy of silicone
      biomaterial (PTQ; Uroplasty BV, Geleen, The Netherlands) injection in the long
      term. METHOD: Six patients, median age 53 years at the time of injection with
      PTQ, were followed up at 61 months. A validated faecal incontinence score,
      treatment-specific questionnaire and SF-36 health survey questionnaire were
      completed. RESULTS: At 61-month follow up one patient had undergone a colostomy
      for faecal incontinence. In the remaining five patients the incontinence score
      was little changed: 11 (8-20) vs 13 (9-19) [pre v at 61 months, median (range)].
      However, there was a substantial improvement in physical and social function on
      the SF-36 scores. Satisfaction scores were high at a median 7 of 10 (range: 0-8).
      Subjectively, three patients were improved; one of these had undergone a further
      set of injections and one improved after a course of biofeedback. After the
      follow-up period one of the five patients had a colostomy for recto-vaginal
      fistula. CONCLUSION: The results of perianal injection of PTQ for passive faecal
      incontinence are variable in the long term. More extensive evaluation in the
      short term, and possibly repeated treatment, may be required.

PMID- 17432991
TI  - Risk factors for impaired healing of the perineal wound after abdominoperineal
      resection of rectum for carcinoma.
AB  - OBJECTIVE: Nonhealing perineal wound is an unpleasant complication of surgical
      excision of the rectum and anus. The aim of the study was to evaluate the risk
      factors for impaired perineal wound healing after abdominoperineal resection
      (APR) of rectum for adenocarcinoma, particularly with the increasing use of neo
      adjuvant chemoradiation. METHOD: The study included 38 consecutive patients (29
      men, nine women; median age 66 years, range: 43-86), who underwent surgical
      excision of rectum and anus for adenocarcinoma from 1999 to 2004. Thirty-seven
      patients underwent APR of rectum and one patient, who developed carcinoma in the
      background of chronic ulcerative colitis, had panproctocolectomy. Associations
      between the failure of the perineal wound to heal and a number of patient, tumour
      and treatment-related variables were evaluated by Pearson chi-square test or
      Fisher's exact test, as appropriate. A P-value of <0.05 was considered
      significant. Multivariate statistical technique of principal component analysis
      was also used to identify risk factors and their relative contribution to
      impaired healing. RESULTS: Impaired healing of the perineal wound was observed in
      10 (26%) of 38 patients. In four of them (11%) the wound remained nonhealed in 1
      year after surgery. Preoperative radiotherapy, delayed primary closure of the
      wound and alcohol consumption in excess of 28 units/week was statistically
      significantly associated with impaired wound healing. Principal component
      analysis identified the following seven factors that cumulatively contributed to
      96% of impaired healing: (i) distant metastases, (ii) preoperative radiotherapy,
      (iii) T-stage of the tumour, (iv) smoking, (v) perioperative blood transfusion,
      (vi) preoperative chemotherapy and (vii) development of side effects of
      preoperative chemoradiation. CONCLUSION: Patients who undergo APR of rectum are
      prone to impaired healing of the perineal wound if radiotherapy is used to treat
      malignancy prior to surgery and wound closure is delayed. In addition, the wound
      may not heal in patients with distant metastases, excessive alcohol consumption,
      present and past smokers and those who suffer adverse effects of preoperative
      chemoradiation and require blood transfusion.

PMID- 17432992
TI  - Laparoscopic colonic resection in fast-track patients does not enhance short-term
      recovery after elective surgery.
AB  - BACKGROUND: Laparoscopic colorectal surgery has been claimed to enhance recovery
      when compared with open surgery. The aim of our study was to investigate whether
      laparoscopic colorectal resection improved recovery with the use of a multimodal
      rehabilitation programme. METHOD: We carried out a prospective audit of 80
      patients undergoing elective colorectal resection between November 2003 and March
      2005. All patients underwent a fast-track protocol with early feeding,
      mobilization and a fluid and sodium restriction regime. Recovery was measured in
      terms of return of gastrointestinal function, hospital stay, complications and
      quality of life measures. RESULTS: Of the 80 patients in the study 22 underwent
      laparoscopic resection and 58 had open surgery. Patients were well matched for
      all baseline characteristics. The groups were not significantly different in
      terms of opioid or antiemetic use. They were also similar in median time to first
      flatus (69 h vs 69 h, P = 0.36) and median time to first bowel motion (127 h vs
      101 h, P = 0.07). There was no difference in median hospital stay (5.8 days vs
      5.9 days, P = 0.87) or complications (P = 0.46) between the laparoscopic and open
      group. There were no significant differences in Short Form 36 scores between the
      two groups for any of the components measured. CONCLUSION: Laparoscopic
      colorectal resection does not appear to reduce the duration of ileus or hospital
      stay with the use of a multimodal rehabilitation regime. Further large randomized
      trials are required to confirm these findings.

PMID- 17432993
TI  - Endoscopically placed caecostomy buttons: a trial ACE procedure.
AB  - The use of the antegrade continence enema (ACE) is becoming more widespread.
      Preliminary studies have been promising, but the procedure is not universally
      successful. A colonoscopic insertion of a caecostomy button is a relatively minor
      procedure. This allows the ACE to be used for a trial period to assess whether a
      permanent procedure would be beneficial. If successful, enemas can be continued
      by the caecostomy, or a formal ACE can be performed. We report a series of five
      patients who underwent staged endoscopic insertion of a MIC-KEY caecostomy
      button, and we discuss the technical aspects of the procedure.

PMID- 17432997
TI  - Time trend of asthma prevalence among school children in Taiwan. [corrected].
AB  - The standardized International Study of Asthma and Allergies in Childhood (ISAAC)
      is a valid tool in assessing prevalence of asthma indices. In order to determine
      the time trends of childhood asthma in Taiwan, we compared data from nationwide
      ISAAC surveys from a very large sample of Taiwanese 12- to 15-year-old school
      children, using ISAAC core written and video questionnaires. The number of
      participants was 44,104 in 1995-96 (phase I) and 11,048 in 2001 (phase III). We
      found a general tendency towards an increase in lifetime prevalence of physician
      diagnosed asthma and asthma symptoms between two surveys, more marked for girls
      than for boys. Most of the 12-month prevalence of asthma symptoms decreased among
      boys but stabilized among girls. When comparing different severity levels, we
      also noted that the decreasing trends of current symptoms were more marked with
      regard to severe symptoms than mild symptoms in both sexes. A combination of both
      improved awareness and management of asthma might in part explain this
      circumstance. Over the past decade in Taiwan, the lifetime prevalence of
      childhood asthma was increasing, more marked among girls; however, the 12-month
      prevalence of asthma symptoms was decreasing, mostly among boys. The exact
      reasons for such trends remain to be explored.

PMID- 17432998
TI  - Gender-specific differences in the prevention of asthma-like symptoms in high
      risk infants.
AB  - The prevalence of asthma in children has increased in the last decades, and
      gender-specific differences in asthma development have recently been suggested.
      The present study investigates whether gender differences are present in a
      population of young children (0-2 yr) with a high risk for the development of
      asthma on the basis of the presence of asthma in first-degree relative(s). The
      study was performed on 222 children (118 boys, 104 girls) with a familial
      predisposition of asthma, which received standardized recommendations to reduce
      exposure to allergens (dust mite, pets and food allergens) and to passive
      smoking. Health outcome (wheezing episodes and shortness of breath) and
      compliance with allergen-reducing measures were studied by means of multiple
      regression analyses. Boys suffered more from asthma-like complaints than girls,
      as diagnosed by the general practitioner (32% vs. 18%, respectively, p = 0.023).
      Compliance with intervention measures was similar for boys and girls for most
      allergens, but food allergen reduction was better applied for girls: duration of
      exclusive breastfeeding was longer in girls (median 9 wk vs. 4 wk, p = 0.009).
      Further analysis showed that 4 wk of longer breastfeeding reduced the number of
      wheezing episodes and shortness of breath in boys by 19% and 15%, respectively,
      but not in girls, suggesting sex as an effect modifier in the relationship
      between breastfeeding and asthma-like symptoms. The present findings indicate
      that application and effects of prevention strategies for children with a high
      risk for developing asthma might be gender-specific and suggest a special
      importance of breastfeeding boys.

PMID- 17432999
TI  - Increased sensitization in urban vs. rural environment--rural protection or an
      urban living effect?
AB  - In a population-based longitudinal cohort study, we tested the hypothesis that
      children growing up in a high-traffic polluted urban area (UA) in the Athens'
      basin have higher prevalence of allergies and sensitization when compared with
      those growing up in a Greek provincial rural area (RA). We recruited 478 and 342
      children aged 8-10 living in the UA and the RA, respectively. Respiratory health
      was assessed by a parent-completed questionnaire in three phases: 1995-96 (phase
      1), 1999-2000 (phase 2), 2003-04 (phase 3) and skin-prick testing to common
      indoor and outdoor aeroallergens was performed at phases 1 and 2. Reported asthma
      and eczema did not differ between the two areas, whereas reported hay fever was
      persistently more prevalent in the UA than in the RA (16.5%, 17.0%, 18.2% vs.
      7.0%, 8.3%, 9.6%, respectively). Sensitization was more prevalent in the UA at
      both phases (19.0% vs. 12.1% in phase 1, 20.0% vs. 14.1% in phase 2). Residential
      area contributed independently to sensitization to >or=1 aeroallergens (OR: 0.29;
      95% CI: 0.13-0.66; p = 0.003) and to polysensitization (OR: 0.28; 95% CI: 0.10
      0.82; p = 0.020) in phase 1. These associations were independent of farming
      practices. No significant contributions were found in phase 2. Our results
      suggest that long-term exposure to urban environment is associated with a higher
      prevalence of hay fever but not of asthma or eczema. The negative association
      between rural living and the risk of atopy during childhood, which is independent
      of farming practices, implies that it is mainly driven by an urban living effect.

PMID- 17433000
TI  - Skin prick testing predicts peanut challenge outcome in previously allergic or
      sensitized children with low serum peanut-specific IgE antibody concentration.
AB  - Peanut allergy is transient in some children but it is not clear whether
      quantitating peanut-specific IgE by Skin Prick Test (SPT) adds additional
      information to fluorescent-enzyme immunoassay (FEIA) in discriminating between
      allergic and tolerant children. To investigate whether SPT with a commercial
      extract or fresh foods adds additional predictive information for peanut
      challenge in children with a low FEIA (<10 k UA/L) who were previously
      sensitized, or allergic to peanuts. Children from a hospital-based allergy
      service who were previously sensitized or allergic to peanuts were invited to
      undergo a peanut challenge unless they had a serum peanut-specific IgE>10 k UA/L,
      a previous severe reaction, or a recent reaction to peanuts (within two years).
      SPT with a commercial extract, raw and roasted saline soaked peanuts was
      performed immediately prior to open challenge in hospital with increasing
      quantity of peanuts until total of 26.7 g of peanut was consumed. A positive
      challenge consisted of an objective IgE mediated reaction occurring during the
      observation period. 54 children (median age of 6.3 years) were admitted for a
      challenge. Nineteen challenges were positive, 27 negative, five were
      indeterminate and three did not proceed after SPT. Commercial and fresh food
      extracts provided similar diagnostic information. A wheal diameter of >or=7 mm of
      the commercial extract predicted an allergic outcome with specificity 97%,
      positive predictive value 93% and sensitivity 83%. There was a tendency for an
      increase in SPT wheal since initial diagnosis in children who remained allergic
      to peanuts while it decreased in those with a negative challenge. The outcome of
      a peanut challenge in peanut sensitized or previously allergic children with a
      low FEIA can be predicted by SPT. In this cohort, not challenging children with a
      SPT wheal of >or=7 mm would have avoided 15 of 18 positive challenges and denied
      a challenge to one out of 27 tolerant children.

PMID- 17433001
TI  - Combining skin prick, immediate skin application and specific-IgE testing in the
      diagnosis of peanut allergy in children.
AB  - Previous studies have suggested various diagnostic cut-offs of allergy tests for
      the diagnosis of clinical peanut allergy in children. There are few data relating
      to the use of combinations of these tests in children. We aimed to determine the
      validity of previously reported diagnostic cut-off levels of peanut allergen skin
      tests and peanut specific-immunoglobulin (Ig) E, as well as the usefulness of
      combinations of these, for predicting clinical peanut allergy in our Allergy
      Clinic. Children attending the Allergy Clinic with a positive peanut skin prick
      test (SPT; n = 84) were included in the study. Immediate skin application food
      tests (I-SAFT) using 1 g of peanut butter (positive if any wheals were detected
      at 15 min), peanut specific-IgE levels and open-label peanut food challenges were
      performed. Fifty-two of 85 peanut challenges were positive. Skin prick test
      specificity was 67% at >or=8 mm and 100% at >or=15 mm. The I-SAFT was 82%
      specific. A peanut specific-IgE level of 0.37 kU/l was 98% sensitive but 33%
      specific. A level of 10 kU/l was 100% specific. Combinations of a SPT of >or=8 mm
      with a positive I-SAFT and a peanut specific-IgE >or=0.37 kU/l were 88% specific
      with a sensitivity of 38%. Using challenge outcomes as the standard, available in
      vitro and in vivo diagnostic tests for peanut allergy have poor sensitivity and
      specificity and combining them does not significantly improve their clinical
      usefulness. Previously described diagnostic cut-off levels do not have general
      applicability. Allergy practitioners may need to interpret results of allergy
      tests in the context of their own practices.

PMID- 17433002
TI  - Atopic dermatitis: quality of life of young Italian children and their families
      and correlation with severity score.
AB  - The aim of this study was to determine the ways in which atopic dermatitis (AD)
      affects the lives of young Italian children and their families, in terms of
      quality of life, and correlate it with AD severity and the perception of severity
      as estimated by the family. The parents of 45 children aged 3-84 months affected
      by AD were asked to complete two validated questionnaires after clinical
      examination. The first questionnaire was about the child's quality of life
      (Infants' Dermatitis Quality of Life Index); the second regarded the family's
      quality of life (Dermatitis Family Impact questionnaire). In a further question
      parents were asked to estimate the severity of the disease of the child.
      Children's quality of life appeared slightly-moderately altered (mean score 10.2)
      compared with the value of a control group (3.3), and itching, sleep problems and
      the influence of the disease on the child's mood were the cause of greatest
      discomfort for the child. Family quality of life appeared moderately altered
      (mean score 11) compared with the value of the control group (7.4). The greatest
      problem was the disturbed sleep of the family members. Other important problems
      were the economic cost for the management of the disease and the tiredness and
      irritability caused by the disease in parents. Analysis of the responses confirms
      the incorrect estimation of the severity of the disease perceived by the family.
      In our opinion, the two questionnaires may be useful in clinical practice to
      understand better the difficulties suffered by a family with a child affected by
      AD. They also provide data that may help to improve the clinical approach for the
      child and the family, and to assess the degree of under-/overestimation of the
      disease by the family.

PMID- 17433003
TI  - Efficacy of donkey's milk in treating highly problematic cow's milk allergic
      children: an in vivo and in vitro study.
AB  - Successful therapy in cow's milk protein allergy rests on completely eliminating
      cow's milk proteins from the child's diet: it is thus necessary to provide a
      replacement food. This prospective study investigated tolerance of donkey's milk
      in a population of 46 selected children with cow's milk protein allergy, for whom
      it was not possible to use any cow's milk substitute. Thirty-eight children
      (82.6%) liked and tolerated donkey's milk at the challenge and for the entire
      duration of follow-up. Catch-up growth was observed in all subjects with growth
      deficit during cow's milk proteins challenge. The degree of cross-reactivity of
      immunoglobulin E (IgE) with donkey's milk proteins was very weak and aspecific.
      Donkey's milk was found to be a valid alternative to both IgE-mediated and non
      IgE-mediated cow's milk proteins allergy, including in terms of palatability and
      weight-height gain.

PMID- 17433004
TI  - The spectrum of cow's milk allergy.
AB  - Childhood cow's milk allergy is a diagnosis encompassing various syndromes.
      Antigen-immunoglobulin E (IgE) antibody interaction is classically involved in
      mast cell degranulation in IgE-mediated food allergy, while non-IgE mediated
      cow's milk allergy is mostly mediated by cellular mechanisms. The diagnosis of
      cow's milk allergy largely relies on a good knowledge of the clinical expression
      of the disease. In this educational review series, we describe three cases of
      cow's milk allergy, first a 7-yr-old girl with persisting IgE-mediated cow's milk
      allergy, second a 8-month-old boy with cow's milk induced flares of atopic
      dermatitis, and third a 6-yr-old boy with sheep and goat milk allergy, in the
      absence of cow's milk allergy. The cases are discussed and summarized with more
      general recommendations for the clinical management of cow's milk allergy.

PMID- 17433007
TI  - Alcohol selectively reduces brain activity during the affective processing of
      negative information.
AB  - BACKGROUND: Although it has frequently been suggested that alcohol influences
      emotions such as anxiety and fear through the modulation of affective information
      processing, few studies addressed this topic using objective measures.
      OBJECTIVES: The acute effects of alcohol on affective processing of pictorial
      stimuli were investigated using electrophysiological measures. METHODS: Event
      related brain potentials (ERP) resulting from watching pleasant, unpleasant, and
      neutral pictures were investigated in a group of participants receiving a
      beverage containing a moderate dose of alcohol (n=26) and a group of participants
      receiving a nonalcoholic placebo beverage (n=24). Both early [early posterior
      negativity (EPN)] and late [late positive potential (LPP)] ERP components were
      employed as index of emotional processing. RESULTS: The results show that alcohol
      reduced brain activity during watching unpleasant information in a late stage
      (700-1000 ms). This suggests that alcohol selectively influences the processing
      of unpleasant information. CONCLUSIONS: The findings are in concordance with
      theories linking alcohol administration to decreased processing of affective
      information. The results are discussed in the context of the role of the effect
      of alcohol on affective information processing, and its relevance to alcoholism.

PMID- 17433008
TI  - Role of appetite-regulating peptides in alcohol craving: an analysis in respect
      to subtypes and different consumption patterns in alcoholism.
AB  - BACKGROUND: A role of appetite-regulating peptides like leptin and ghrelin in the
      neurobiology of alcohol craving has been proposed by several studies. Aim of this
      analysis was to search for differences regarding an association between these
      peptides and alcohol craving with respect to different subtypes and beverage
      consumption patterns in patients with alcohol dependence. METHODS: We analyzed a
      sample of 188 patients at admission for alcohol detoxification regarding leptin
      and ghrelin (n=117) serum levels. Craving was measured using the Obsessive
      Compulsive Drinking Scale (OCDS). Patients were classified according to Lesch's
      typology of alcohol dependence and according to their preferred type of alcoholic
      beverage (beer, wine, spirits). RESULTS: Using general linear models to analyze a
      possible interaction between subtypes and leptin/ghrelin levels with respect to
      craving, we found a significant positive association for leptin in patients of
      Lesch's types 1 and 2, and in patients consuming beer or wine. Ghrelin levels
      showed a significant trend regarding an association with craving in patients of
      Lesch's type 1. In the other subgroups we found no significant results.
      CONCLUSIONS: Our findings show that appetite-regulating peptides may be of
      special importance regarding alcohol craving in subtypes of patients. This may
      explicate at least in part previous contradictory findings.

PMID- 17433009
TI  - Lactational state modifies alcohol pharmacokinetics in women.
AB  - BACKGROUND: Given the physiological adaptations of the digestive system during
      lactation, the present study tested the hypothesis that lactation alters alcohol
      pharmacokinetics. METHODS: Lactating women who were exclusively breastfeeding a 2
      to 5-month-old infant and 2 control groups of nonlactating women were studied.
      The first control group consisted of women who were exclusively formula-feeding
      similarly aged infants, whereas the other consisted of women who had never given
      birth. A within-subjects design study was conducted such that women drank a 0.4
      g/kg dose of alcohol following a 12-hour overnight fast during one test session
      (fasted condition) or 60 minutes after consuming a standard breakfast during the
      other (fed condition). Blood alcohol concentration (BAC) levels and mood states
      were obtained at fixed intervals before and after alcohol consumption. RESULTS:
      Under both conditions, the resultant BAC levels at each time point were
      significantly lower and the area under the blood alcohol time curve were
      significantly smaller in lactating women when compared with the 2 groups of
      nonlactating women. That such changes were due to lactation per se and not due to
      recent parturient events was suggested by the finding that alcohol
      pharmacokinetics of nonlactating mothers, who were tested at a similar time
      postpartum, were no different from women who had never given birth. Despite lower
      BAC levels in lactating mothers, there were no significant differences among the
      3 groups of women in the stimulant effects of alcohol. However, lactating women
      did differ in the sedative effects of alcohol when compared with nulliparous but
      not formula-feeding mothers. That is, both groups of parous women felt sedated
      for shorter periods of time when compared with nulliparous women. CONCLUSIONS:
      The systemic availability of alcohol was diminished during lactation. However,
      the reduced availability of alcohol in lactating women did not result in
      corresponding changes in the subjective effects of alcohol.

PMID- 17433010
TI  - An advanced sheep (Ovis aries, 2n = 54) cytogenetic map and assignment of 88 new
      autosomal loci by fluorescence in situ hybridization and R-banding.
AB  - Presented herein is an updated sheep cytogenetic map that contains 452 loci (291
      type I and 161 type II) assigned to specific chromosome bands or regions on
      standard R-banded ideograms. This map, which significantly extends our knowledge
      of the physical organization of the ovine genome, includes new assignments for 88
      autosomal loci, including 74 type I loci (known genes) and 14 type II loci
      (SSRs/microsatellite marker/STSs), by FISH-mapping and R-banding. Comparison of
      the ovine map to the cattle and goat cytogenetic maps showed that common loci
      were located within homologous chromosomes and chromosome bands, confirming the
      high level of conservation of autosomes among ruminant species. Eleven loci that
      were FISH-mapped in sheep (B3GAT2, ASCC3, RARSL, BRD2, POLR1C, PPP2R5D, TNRC5,
      BAT2, BAT4, CDC5L and OLA-DRA) are unassigned in cattle and goat. Eleven other
      loci (D3S32, D1S86, BMS2621, SFXN5, D5S3, D5S68, CSKB1, D7S49, D9S15, D9S55 and
      D29S35) were assigned to specific ovine chromosome (OAR) bands but have only been
      assigned to chromosomes in cattle and goat.

PMID- 17433011
TI  - A QTL study of growth and body shape in the inter-species hybrid of Pere David's
      deer (Elaphurus davidianus) and red deer (Cervus elaphus).
AB  - An interspecies deer hybrid resource population developed from a cross of Pere
      David's and red deer was used to detect QTL that account for species differences.
      A genome scan, coupled with composite interval mapping, was conducted to search
      for QTL controlling body measurements at pre-pubescent age (6 months of age) and
      puberty (15 months of age) in this interspecies hybrid. Five linkage groups that
      harbour QTL affecting morphology were identified. A joint-traits analysis was
      used to search for putative pleiotropic QTL on four of these linkage groups, and
      three were significantly associated with pleiotropic QTL for nose width and foot
      length (metacarpal and phalanges), which collectively accounted for 29-58% of the
      phenotypic difference between the two deer species. This study suggests that a
      few loci with large pleiotropic effects may be responsible for species-specific
      differences in growth and structure-related traits.

PMID- 17433012
TI  - The locus for bovine dilated cardiomyopathy maps to chromosome 18.
AB  - Bovine dilated cardiomyopathy (BDCMP) is a severe and terminal disease of the
      heart muscle observed in Holstein-Friesian cattle over the last 30 years. There
      is strong evidence for an autosomal recessive mode of inheritance for BDCMP. The
      objective of this study was to genetically map BDCMP, with the ultimate goal of
      identifying the causative mutation. A whole-genome scan using 199 microsatellite
      markers and one SNP revealed an assignment of BDCMP to BTA18. Fine-mapping on
      BTA18 refined the candidate region to the MSBDCMP06-BMS2785 interval. The
      interval containing the BDCMP locus was confirmed by multipoint linkage analysis
      using the software loki. The interval is about 6.7 Mb on the bovine genome
      sequence (Btau 3.1). The corresponding region of HSA19 is very gene-rich and
      contains roughly 200 genes. Although telomeric of the marker interval, TNNI3 is a
      possible positional and a functional candidate for BDCMP given its involvement in
      a human form of dilated cardiomyopathy. Sequence analysis of TNNI3 in cattle
      revealed no mutation in the coding sequence, but there was a G-to-A transition in
      intron 6 (AJ842179:c.378+315G>A). The analysis of this SNP using the study's
      BDCMP pedigree did not conclusively exclude TNNI3 as a candidate gene for BDCMP.
      Considering the high density of genes on the homologous region of HSA19, further
      refinement of the interval on BTA18 containing the BDCMP locus is needed.

PMID- 17433013
TI  - A polymorphism within the equine CRISP3 gene is associated with stallion
      fertility in Hanoverian warmblood horses.
AB  - Fertility of stallions is of high economic importance, especially for large
      breeding organisations and studs. Breeding schemes with respect to fertility
      traits and selection of stallions at an early stage may be improved by including
      molecular genetic markers associated with traits. The genes coding for equine
      cysteine-rich secretory proteins (CRISPs) are promising candidate genes because
      previous studies have shown that CRISPs play a role in the fertilising ability of
      male animals. We have previously characterised the three equine CRISP genes and
      identified a non-synonymous polymorphism in the CRISP1 gene. In this study, we
      report one non-synonymous polymorphism in the CRISP2 gene and four non-synonymous
      polymorphisms in the CRISP3 gene. All six CRISP polymorphisms were genotyped in
      107 Hanoverian breeding stallions. Insemination records of stallions were used to
      analyse the association between CRISP polymorphisms and fertility traits. Three
      statistical models were used to evaluate the influence of single mutations,
      genotypes and haplotypes of the polymorphisms. The CRISP3 AJ459965:c.+622G>A SNP
      leading to the amino acid substitution E208K was significantly associated with
      the fertility of stallions. Stallions heterozygous for the CRISP3 c.+622G>A SNP
      had lower fertility than homozygous stallions (P = 0.0234). The pregnancy rate
      per cycle in these stallions was estimated to be approximately 7% lower than in
      stallions homozygous at this position.

PMID- 17433014
TI  - Single nucleotide polymorphisms for pig identification and parentage exclusion.
AB  - Single nucleotide polymorphisms (SNPs) have become an important type of marker
      for commercial diagnostic and parentage genotyping applications as automated
      genotyping systems have been developed that yield accurate genotypes.
      Unfortunately, allele frequencies for public SNP markers in commercial pig
      populations have not been available. To fulfil this need, SNP markers previously
      mapped in the USMARC swine reference population were tested in a panel of 155
      boars that were representative of US purebred Duroc, Hampshire, Landrace and
      Yorkshire populations. Multiplex assay groups of 5-7 SNP assays/group were
      designed and genotypes were determined using Sequenom's massarray system. Of 80
      SNPs that were evaluated, 60 SNPs with minor allele frequencies >0.15 were
      selected for the final panel of markers. Overall identity power across breeds was
      4.6 x 10(-23), but within-breed values ranged from 4.3 x 10(-14) (Hampshire) to
      2.6 x 10(-22) (Yorkshire). Parentage exclusion probability with only one sampled
      parent was 0.9974 (all data) and ranged from 0.9594 (Hampshire) to 0.9963
      (Yorkshire) within breeds. Sire exclusion probability when the dam's genotype was
      known was 0.99998 (all data) and ranged from 0.99868 (Hampshire) to 0.99997
      (Yorkshire) within breeds. Power of exclusion was compared between the 60 SNP and
      10 microsatellite markers. The parental exclusion probabilities for SNP and
      microsatellite marker panels were similar, but the SNP panel was much more
      sensitive for individual identification. This panel of SNP markers is
      theoretically sufficient for individual identification of any pig in the world
      and is publicly available.

PMID- 17433015
TI  - Mutations within the FGF5 gene are associated with hair length in cats.
AB  - Hereditary hair length variability in mice and dogs is caused by mutations within
      the fibroblast growth factor 5 (FGF5) gene. The aim of this study was to evaluate
      the feline FGF5 orthologue as a functional candidate gene for the long hair
      phenotype in cats, which is recessive to short hair. We amplified the feline FGF5
      cDNA and characterised two alternatively spliced transcripts by RT-PCR.
      Comparative cDNA and genomic DNA sequencing of long- and short-haired cats
      revealed four non-synonymous polymorphisms in the FGF5 coding sequence. A
      missense mutation (AM412646:c.194C>A) was found in the homozygous state in 25
      long-haired Somali, Persian, Maine Coon, Ragdoll and crossbred cats. Fifty-five
      short-haired cats had zero or one copy of this allele. Additionally, we found
      perfect co-segregation of the c.194C>A mutation within two independent pedigrees
      segregating for hair length. A second FGF5 exon 1 missense mutation
      (AM412646:c.182T>A) was found exclusively in long-haired Norwegian Forest cats.
      The c.182T>A mutation probably represents a second FGF5 mutation responsible for
      long hair in cats. In addition to the c.194C>A mutation, a frameshift mutation
      (AM412646:c.474delT) was found with a high frequency in the long-haired Maine
      Coon breed. Finally, a missense mutation (AM412646:c.475A>C) was also associated
      with the long-haired phenotype in some breeds. However, as one short-haired cat
      was homozygous for this polymorphism, it is unlikely that it has a functional
      role in the determination of hair length.

PMID- 17433016
TI  - Genomic analysis of genetic markers associated with inherited cardiomyopathy
      (round heart disease) in the turkey (Meleagris gallopavo).
AB  - In turkeys, spontaneous cardiomyopathy or round heart (RH) disease is
      characterised by dilated ventricles and cardiac muscle hypertrophy. Although the
      aetiology of RH is still unknown, the disease can have a significant economic
      impact on turkey producers. In an initial attempt to identify genomic regions
      associated with RH, we utilised the chicken genome sequence to target short DNA
      sequences (sequence-characterised amplified regions, SCARs) identified in
      previous studies that had significant differences in frequency distribution
      between RH+ and RH- turkeys. SCARs were comparatively aligned with the chicken
      whole-genome sequence to identify flanking regions for primer design. Primers
      from 32 alignments were tested and target sequences were successfully amplified
      for 30 loci (94%). Comparative re-sequencing identified putative SNPs in 20 of
      the 30 loci (67%). Genetically informative SNPs at 16 loci were genotyped in the
      UMN/NTBF turkey mapping population. As a result of this study, 34 markers were
      placed on the turkey/chicken comparative map and 15 markers were added to the
      turkey genetic linkage map. The position of these markers relative to cardiac
      related genes is presented. In addition, analysis of genotypes at 109
      microsatellite loci presumed to flank the SCAR sequences in the turkey genome
      identified four significant associations with RH.

PMID- 17433017
TI  - Identification of single nucleotide polymorphisms in the bovine CCL2, IL8, CCR2
      and IL8RA genes and their association with health and production in Canadian
      Holsteins.
AB  - The aim of this study was to identify the presence of SNPs in the chemokine genes
      CCL2 and IL8 and the chemokine receptor genes IL8RA and CCR2, and assess their
      potential contribution to variation in estimated breeding values (EBVs) for
      somatic cell score (SCS) and four other traits in Canadian Holstein bulls. Pools
      of DNA for bulls with high (H) and low (L) EBVs for SCS were used for
      identification of 11 SNPs. Two unreported SNPs were found in the CCL2 gene and
      one SNP was found in the CCR2 gene. Previously reported SNPs (three in the IL8
      gene and five in the IL8RA chemokine receptor) were also identified. Two SNPs in
      CCL2, three in IL8, one in IL8RA and one in CCR2 were genotyped in Canadian
      Holstein bulls (n = 338) using tetra primer ARMS-PCR. We investigated
      associations of these seven polymorphisms with three production traits (milk
      yield, fat yield and protein yield) and one conformation trait related to
      mastitis (udder depth). The allele substitution effect for the CCL2
      rs41255713:T>C SNP was significant at an experimental-wise level for milk yield
      (247.5 +/- 79.9 kg) and protein yield (7.4 +/- 2.3 kg) EBVs (P <or= 0.05). The
      associations of the SNPs with SCS EBVs were not significant at an experimental
      wise level. However, the allele substitution effect of the CCR2 rs41257559:C>T
      SNP on SCS was significant at the comparison-wise level (-0.04 +/- 0.02, P =
      0.05), which might indicate a possible association in support of other published
      studies. Lastly, we assigned CCR2 to BTA22q24, where a previously QTL for SCS was
      identified.

PMID- 17433018
TI  - Case-control study supports extension of surveillance interval after colonoscopic
      polypectomy to at least 5 yr.
AB  - OBJECTIVE: Colonoscopy with removal of polyps may strongly reduce colorectal
      cancer (CRC) incidence and mortality. Recommended time intervals to surveillance
      colonoscopy differ between countries and have recently been extended to 5 yr or
      longer for the majority of cases in the United States. Whereas previous evidence
      is mainly based on observations of adenoma recurrence, we aimed to assess risk of
      CRC occurrence according to time since polypectomy. METHODS: In a population
      based case-control study conducted in Germany, detailed history and results of
      previous large bowel endoscopies were obtained by interview and from medical
      records. Risk of CRC among subjects with history of endoscopic polypectomy
      compared to subjects without previous large bowel endoscopy was assessed
      according to time since polypectomy among 454 cases with CRC and 391 matched
      controls. RESULTS: Odds ratios (95% confidence intervals) of CRC up to 2 yr, 3-5
      yr, and 6-10 yr after polypectomy (using subjects without previous endoscopy as
      reference group) were 0.16 (0.09-0.69), 0.27 (0.08-0.87), and 1.90 (0.67-5.43),
      respectively. Risk was significantly reduced (odds ratio 0.27, 95% confidence
      interval 0.10-0.77) within 5 yr even after detection and removal of high-risk
      polyps (3+ polyps, at least 1 polyp > or =1 cm, at least 1 polyp with villous
      components). Odds ratios (95% confidence intervals) for the entire 10-yr time
      interval following polypectomy were 0.50 (0.23-1.12) and 0.36 (0.18-0.76) for
      patients with recorded high-risk adenomas and other patients, respectively.
      CONCLUSIONS: Our study provides empirical support for extension of the
      surveillance interval after colonoscopic polypectomy to at least 5 yr.

PMID- 17433019
TI  - Detection of intestinal metaplasia in Barrett's esophagus: an observational
      comparator study suggests the need for a minimum of eight biopsies.
AB  - OBJECTIVES: Intestinal metaplasia (IM) and dysplasia in Barrett's esophagus are
      recognized surrogates for esophageal adenocarcinoma risk. While few would argue
      with the "hunt for dysplasia," there is a divide regarding the usefulness of the
      histological confirmation of intestinal metaplasia in endoscopically apparent
      long segment Barrett's esophagus. We aimed to assess the frequency of intestinal
      metaplasia in 125 consecutive patients with columnar-lined esophagus and to
      determine the optimal biopsy protocol to detect intestinal metaplasia. METHODS:
      Two-hundred ninety-six endoscopies were performed over a 4-yr period in Barrett's
      esophagus segments of mean length 4 cm (range 1-11 cm) at a single center and the
      resulting biopsies were analyzed retrospectively. Biopsies were all processed
      with routine hematoxylin and eosin (H&E) staining, and a subset (N=92) was
      subject to alcian blue/periodic-acid Schiff staining. RESULTS: Using H&E
      staining, we found that the optimum number of biopsies to diagnose intestinal
      metaplasia was 8 per endoscopy, mean 67.9% endoscopies having intestinal
      metaplasia. In contrast, if only four were taken the yield was 34.7% with
      intestinal metaplasia. Unless more than 16 biopsies were taken (100% yield of
      intestinal metaplasia), no additional significant detection was achieved. Using
      additional alcian blue/periodic-acid Schiff staining only had a marginal benefit,
      with 5.4% of new cases of intestinal metaplasia being identified. There is a
      proximal cephalo-caudal gradient of intestinal metaplasia, especially with
      increased chronological age, but doing repeat endoscopies on patients did not
      increase the detection of intestinal metaplasia. CONCLUSIONS: The data suggest
      that at least 8 random biopsies is the minimum to be taken and analyzed with
      conventional H&E staining to diagnose benign intestinal metaplasia. Taking more
      biopsies did not statistically increase the diagnosis of intestinal metaplasia
      except when greater than 16 were taken when 100% yield was obtained.

PMID- 17433020
TI  - Left atrial volume: a novel predictor of hepatopulmonary syndrome.
AB  - OBJECTIVES: We studied patients with hepato-pulmonary syndrome (HPS). We found
      that HPS is frequently present in patients with left atrial enlargement. The aim
      of this prospective study was to evaluate the possible correlation between left
      atrial volume and HPS. METHODS: Adult patients (>18 yr old) with biopsy proven
      liver cirrhosis who were referred for liver transplantation were enrolled in the
      study. Diagnosis of HPS was established when the following points were fulfilled:
      (a) the presence of chronic liver disease, (b) increased alveolar-arterial
      difference (AaDO(2)), (c) intrapulmonary vascular dilatation, and (d) absence of
      primary cardiac or pulmonary disease. RESULTS: We enrolled 41 patients (mean age
      47.1 +/- 10.6 yr) diagnosed with HPS. Also 108 Child-Pugh score matched cirrhotic
      patients (mean age 49.2 +/- 9.3 yr) who have negative contrast echocardiography
      and normal age-related AaDO(2) were selected as a control group for the purpose
      of comparison of left atrial volume (LAV). LAV was significantly greater in
      patients with HPS compared to the control group (55.1 +/- 7.5 mL vs 37.1 +/- 9.3
      mL, P < 0.05). The area under the receiver-operating characteristic (ROC) curve
      for LAV was 0.903 (Cut point >/= 50 mL, sensitivity 86.3%, specificity 81.2%).
      CONCLUSION: In the context of liver cirrhosis, LAV >/= 50 mL is a simple and
      feasible parameter to detect HPS.

PMID- 17433021
TI  - Are chronic hepatitis C viral infections more benign in patients with hemophilia?
AB  - BACKGROUND AND AIMS: Cirrhosis is associated with thromboses of the intrahepatic
      vasculature. This raises the possibility that HCV infections in hemophiliacs may
      differ from those in non-hemophiliacs METHODS: Liver biopsy findings from 12
      hemophiliacs and 20 age- and gender-matched, non-hemophiliac controls with
      chronic hepatitis C viral (HCV) infections were compared for inflammatory
      activity and fibrosis. RESULTS: The mean ages of hemophiliacs and controls were
      35.0 +/- 3.0 yr and 39.6 +/- 5.6 yr, respectively (P= 0.2). Serum aspartate
      aminotransferase (AST) levels were lower (44 +/- 13 vs 70 +/- 43 U/L) and the
      duration of the partial thromboplastin (PTT) time longer (49.2 +/- 16.9 vs 31.2
      +/- 1.2 s.) in hemophiliacs than in controls (P < 0.02 and <0.001, respectively).
      Six of the seven hemophiliac patients (86%) and 8/17 controls (46%) were infected
      with genotypes 1a or 1b with the remainder being infected with 2b, 3a, or 3b.
      Histological activity and fibrosis scores were significantly lower in
      hemophiliacs than in controls (1.9 +/- 0.6 vs 3.6 +/- 2.7 and 0.3 +/- 0.2 vs 1.5
      +/- 1.5, P < 0.05 and P < 0.01, respectively). None of the hemophiliacs had
      histological evidence of advanced disease (bridging fibrosis and/or cirrhosis) as
      compared to 7/20 (30%) controls (P < 0.05). CONCLUSION: HCV infections in
      hemophiliacs may be less severe than in HCV infected patients without hemophilia.

PMID- 17433022
TI  - Cholangiocarcinoma in young individuals with and without primary sclerosing
      cholangitis.
AB  - OBJECTIVES: We aimed at characterizing the clinical presentation and prognosis of
      cholangiocarcinoma in youth with and without primary sclerosing cholangitis
      (PSC). METHODS: Thirteen patients < or =25 yr of age with cholangiocarcinoma with
      or without PSC seen at the Mayo Clinic in Rochester, MN from 1980 to 2005 were
      identified. RESULTS: Of the 13 patients with cholangiocarcinoma, 8 had
      concomitant PSC and 5 did not. PSC was the associated risk factor in 8/13 (61.5%)
      whereas PSC was present in only 321/2,014 (15.9%) cases with cholangiocarcinoma
      in patients older than 25 (P < 0.0001) seen in the same period of time. Seven of
      the eight (88%) patients with cholangiocarcinoma and PSC had IBD and 5 of the 7
      (71%) had Crohn's disease. A mean 11 months transplant free survival was observed
      (range 3-20 months) in cholangiocarcinoma with PSC versus 8 months in
      cholangiocarcinoma patients without PSC (NS). CONCLUSIONS: Cholangiocarcinoma is
      a rare disorder in young adults and it seems not to exist in children. The youth
      group of cholangiocarcinoma plus PSC seems to have a higher prevalence of Crohn's
      disease whereas the prognosis of cholangiocarcinoma in youth seems to be
      similarly poor as described in older patients with cholangiocarcinoma.

PMID- 17433023
TI  - Choroidal neovascularization secondary to Sorsby fundus dystrophy treated with
      systemic bevacizumab (Avastin).
AB  - PURPOSE: A case of choroidal neovascularization (CNV) secondary to Sorsby fundus
      dystrophy (SFD) treated with systemic bevacizumab (Avastin). METHODS: A 41-year
      old woman presented with CNV secondary to SFD in her better eye. The patient
      received three initial infusions of bevacizumab at a dose of 5 mg/kg at 2 week
      intervals and one additional infusion because of CNV recurrence at the 7 month
      follow-up. RESULTS: At 16 month follow-up, visual acuity had improved from 20/50
      at baseline to 20/25; optical coherence tomography and fluorescein angiography
      showed no evidence of CNV activity. CONCLUSION: Systemic bevacizumab seems to be
      a promising treatment option for CNV secondary to SFD.

PMID- 17433024
TI  - Proliferation and apoptosis in mammary epithelium during the rat oestrous cycle.
AB  - AIM: During each oestrous cycle, the mammary gland is subject to changes in
      ovarian hormone levels. It responds with limited proliferation, differentiation
      and regression. To understand the processes resulting in these changes,
      particularly the regulation of cell death, we examined protein levels in mammary
      epithelium during the oestrous cycle of the Sprague-Dawley rat. METHODS: Studies
      of serum hormone levels, vaginal smears, uterine weight and morphology, mammary
      gland morphology, proliferation and apoptotic indices, and protein levels during
      the stages of the Sprague-Dawley rat oestrous cycle were used to examine the
      response of mammary epithelium to the oestrous cycle. RESULTS: Proliferation of
      mammary epithelium was greater in diestrus and proestrus, while apoptosis was
      increased in metestrus and diestrus. Growth factor-, hormone- and anchorage
      mediated cell survival signalling, indicated by activation of Stat5A, FAK and Akt
      1 and expression of anti-apoptotic Bcl-2 family members, was greater in proestrus
      and reduced in metestrus. In contrast, the levels of pro-apoptotic Bcl-2 family
      members and proteins associated with apoptosis in mammary epithelium (TGFbeta3,
      pStat3) were increased during metestrus and diestrus. CONCLUSION: Decreases in
      growth factor, hormone and cell attachment survival signals corresponded with
      increased apoptosis during the second half of the oestrous cycle. The protein
      levels detected during oestrus suggest parallels to apoptosis in mammary
      involution.

PMID- 17433025
TI  - Absolute lymphocyte count predicts therapeutic efficacy of rituximab therapy in
      follicular lymphomas.
AB  - The immunologic mechanisms of action of rituximab include complement mediated
      lysis and antibody-dependent cellular cytotoxicity. We hypothesised that a
      stronger host immune system prior to rituximab therapy for follicular (grades
      1and 2) lymphomas (FL) would result in better response rates and longer time to
      progression (TTP). Thus, we studied the role of absolute lymphocyte count (ALC)
      prior to rituximab therapy on treatment efficacy and TTP in FL patients. Between
      1996 and 2002, 79 FL patients were treated with single agent rituximab during
      their lymphoma treatment at the Mayo Clinic. The median age of the cohort was
      56.6 years (range: 25-98 years). The median TTP was 12.5 months (range: 1-76
      months). Superior TTP was observed with an ALC > or =0.89 x 10(9)/l (n = 40)
      compared with an ALC <0.89 x 10(9)/l (n = 39) at the time of rituximab therapy
      (median: 36.5 vs. 8.1 months, respectively, P < 0.0009). Higher complete response
      rates were observed in the ALC > or =0.89 x 10(9)/l (23/40, 58%) compared with
      the ALC <0.89 x 10(9)/l (5/39, 13%) (P < 0.0001). Multivariate analysis showed
      ALC to be an independent predictor for TTP. This study supports our hypothesis
      that a higher ALC predicts longer TTP following rituximab therapy.

PMID- 17433026
TI  - Successful treatment of thrombotic microangiopathy after haematopoietic stem cell
      transplantation with rituximab.
AB  - Thrombotic microangiopathy (TMA) is a grave complication after haematopoietic
      stem cell transplantation (HSCT) and effective treatment is undefined. Five
      patients with postHSCT TMA, which was refractory to at least 1 week of plasma
      exchange and prednisolone, were treated with rituximab (375 mg/m(2)/week x 4).
      Remission was achieved in four patients, of whom three remained in remission and
      one had died of sepsis at a median follow-up of 10 months. ADAMTS13 levels were
      low in all evaluable patients, and only one patient showed significant anti
      ADAMTS13 antibody. The levels of ADAMTS13 and anti-ADAMTS13 antibody did not
      change significantly with rituximab-induced remission.

PMID- 17433027
TI  - Low-dose lenograstim is as effective as standard dose in shortening neutrophil
      engraftment time following myeloablative chemotherapy and peripheral blood
      progenitor cell rescue.
AB  - Granulocyte colony-stimulating factor (G-CSF) is widely used following
      myeloablative chemotherapy (high-dose therapy; HDT) and peripheral blood
      progenitor cell rescue (PBPCR) to reduce neutrophil engraftment time. The dose
      and duration required to gain maximum clinical and economic benefit has not been
      fully investigated. This double blind placebo-controlled randomised trial was
      performed to determine whether short course low-dose or standard-dose Lenograstim
      (L) would influence recovery of haematopoiesis following HDT and PBPCR. Sixty-one
      patients were randomised between May 1999 and November 2004, to receive standard
      dose lenograstim (263 microg/d), low-dose lenograstim (105 microg/d) or placebo
      injections. These commenced on day +5 following PBPCR and continued until
      neutrophil engraftment [absolute neutrophil count (ANC)] > or = 0.5 x 10(9)/l.
      Patients received standard supportive care until haemopoietic recovery. Both
      standard- and low-dose lenograstim resulted in a significantly shorter median
      time to neutrophil recovery (ANC > or = 0.1 x 10(9)/l:10.0 vs. 11.0 d, P = 0.025;
      ANC > or = 0.5 x 10(9)/l:11.0 vs. 14.0 d, P = 0.0002) compared with placebo.
      There was no significant difference in blood product support, antibiotic usage,
      documented infection, overall survival or relapse-free survival between the
      groups. Short course low-dose lenograstim is as effective as standard-dose in
      reducing neutrophil engraftment time following HDT and PBPCR.

PMID- 17433028
TI  - Pelvic floor muscle training to improve urinary incontinence after radical
      prostatectomy: a systematic review of effectiveness.
AB  - OBJECTIVE: To evaluate the effectiveness of pelvic floor muscle training (PFMT)
      for treating urinary incontinence (UI) after radical prostatectomy (RP) by
      reviewing evidence from randomized trials. METHODS: Randomized trials published
      in English were included if they involved men with UI after RP and compared PFMT
      with a control group. Data were abstracted onto a standardized form using a
      prospectively developed protocol. RESULTS: Eleven trials randomizing 1028 men
      (mean age 64 years) met the inclusion criteria; the duration of the trials was 3
      12 months. One trial of 300 men found that those assigned to PFMT achieved
      continence more quickly (after 1, 3 and 6 months) than men not assigned to PFMT.
      Men receiving biofeedback-enhanced PFMT were more likely to achieve continence or
      have no continual leakage than those with no training within 1-2 months after RP
      (relative benefit increase 1.54; 95% confidence interval 1.01-2.34; four trials
      reporting). The relative benefit increase (1.19, 0.82-1.72; five studies) was no
      longer significant after 3-4 months. Biofeedback-enhanced PFMT was comparable to
      written/verbal PFMT instruction. Extracorporeal magnetic innervation (ExMI) and
      electrical stimulation (ES) were found to be initially (within 1-2 months) more
      effective than PFMT in one trial, but there were no significant differences
      between groups at > or = 3 months. CONCLUSION: Based on available evidence, PFMT
      with or without biofeedback enhancement hastens the return to continence more
      than no PFMT in men with UI after RP. Additional trials are needed to confirm
      whether ExMI and ES are effective conservative treatment options.

PMID- 17433029
TI  - Organ-sparing surgery does not lead to greater antisperm antibody levels than
      orchidectomy.
AB  - OBJECTIVE: To assess a possible development of antisperm antibodies (ASA),
      present in a high percentage of infertile patients, after organ-sparing surgery
      for small testicular tumours, to identify any additional immunogenic effect of
      this procedure compared with standard orchidectomy. PATIENTS AND METHODS: Samples
      of sera were assessed from 54 men who had had surgery between 2000 and 2005 for
      testicular tumour; the men were divided into two groups, i.e. group A (23) had
      had organ-sparing tumour resection and group B (31) had had inguinal
      orchidectomy. Other possible causes of ASA besides testicular tumour were
      excluded in all patients. The blood samples were obtained during follow-up visits
      and the circulating ASA in serum determined using an enzyme-linked immunosorbent
      assay. RESULTS: The mean (range) tumour diameter was statistically significantly
      greater (P < 0.03) in group B, at 33.6 (2-130) mm, than in group A, at 12 (2-30)
      mm. There were significantly more stromal tumours in group A than group B (P <
      0.02). Most importantly, the mean (range) ASA levels were not statistically
      significantly (P > 0.3) higher in group A, at 29 (15-59) U/mL, than in group B,
      at 24.8 (12-39) U/mL. There was also no statistically significant correlation
      between ASA levels and clinical stage, length of follow-up after therapy, patient
      age, tumour size and type of histology. CONCLUSION: From these data, organ
      sparing surgery does not lead to greater ASA levels than orchidectomy and
      patients are therefore at no greater risk of developing an autoimmune
      infertility.

PMID- 17433030
TI  - Is extracorporeal shock wave lithotripsy the preferred treatment option for
      elderly patients with urinary stone? A multivariate analysis of the effect of
      patient age on treatment outcome.
AB  - OBJECTIVES: To investigate the effect of patient age on the stone-free rate (SFR)
      in patients with urinary calculi treated by extracorporeal shockwave lithotripsy
      (ESWL). PATIENTS AND METHODS: In all, 2192 solitary radio-opaque urinary stones
      of 5-15 mm were identified in adult patients receiving primary ESWL. Patients
      were divided into three age groups, i.e. < or = 40, 41-60 and >60 years (579,
      1026 and 587 patients, respectively). Multiple logistic regression was used to
      assess the effect of age and other possible predicting factors (gender, stone
      characteristics, e.g. side, site and size, and the type of lithotripter used) on
      the SFR at 3 months after treatment. RESULTS: The overall adjusted odds ratios
      (95% confidence interval) for the SFR for those aged 41-60 and >60 years (taking
      those aged < or= 40 years as the reference) were 0.708 (0.573-0.875; P = 0.001)
      and 0.643 (0.506-0.818; P < 0.001). However, if the patients were divided into
      those with renal or ureteric stones, only the SFR of the former was affected by
      age, and the adjusted odds ratios were 0.665 (0.512-0.864; P = 0.002) and 0.629
      (0.470-0.841; P = 0.002), respectively. Ageing had no effect on the SFR for
      ureteric stones. CONCLUSION: The SFR after ESWL for renal stones, but not
      ureteric stones, was significantly lower in older patients. Further studies on
      the effects of ageing on renal stone clearance after ESWL are needed to improve
      stone management in the elderly population.

PMID- 17433031
TI  - The prognostic significance of p53, Ki-67, epithelial cadherin and matrix
      metalloproteinase-9 in penile squamous cell carcinoma treated with surgery.
AB  - OBJECTIVE: To evaluate the prognostic significance of p53, Ki-67, epithelial
      cadherin (E-cadherin) and matrix metalloproteinase-9 in primary penile cancer, as
      the presence of lymph node metastasis and long-term survival are hard to define
      in penile squamous cell carcinoma. PATIENTS AND METHODS: Paraffin-embedded
      primary tumour samples were obtained from 73 Chinese patients who had penile
      amputation and regional lymphadenectomy. The expression of molecular markers was
      determined by immunohistochemistry. Logistic regression was used to identify
      factors associated with lymph node metastasis, and a Cox proportional-hazards
      model was used to measure cancer-specific survival (CSS). RESULTS: Thirty (41%)
      patients presented with nodal disease and the 3-year CSS rate for all patients
      was 72%. Lymph node metastasis was significantly correlated with tumour stage,
      histological grade, lymphatic and vascular embolization, and the expression of
      p53, Ki-67 and E-cadherin. By multivariate analysis, tumour embolization and the
      expression of p53 were independent predictors of metastasis. Survival analysis
      showed that the expression of p53 was an independent prognostic factor for CSS.
      In stage T1 tumours, high expression of p53 was significantly associated with
      metastasis and poor survival. CONCLUSION: Lymphatic and vascular embolization,
      and p53 immunoreactivity, are helpful in establishing the probability of lymph
      node metastasis. The expression of p53 is an independent predictor of CSS in
      Chinese patients with penile cancer. In stage T1 tumours, p53 staining is an
      important variable determining the prognosis and treatment outcome.

PMID- 17433032
TI  - Management of small indeterminate renal tumours: is there a case for needle
      biopsy?

PMID- 17433033
TI  - The value of three-dimensional transrectal ultrasonography in staging prostate
      cancer.
AB  - OBJECTIVE: To use three-dimensional transrectal ultrasonography (3D-TRUS) to
      reconstruct the prostate, and thus determine its value in staging clinically
      localized prostate cancer. PATIENTS AND METHODS: In all, 180 patients with newly
      diagnosed clinically localized prostate cancer were assessed using 3D-TRUS for
      staging. TRUS findings were compared with histopathological staging after radical
      prostatectomy. RESULTS: Pathological staging of specimens showed extracapsular
      extension in 69 patients, of whom 53 had pathological capsular perforation and 16
      had seminal vesicle invasion. 3D-TRUS identified 58 patients with sites of
      extracapsular extension with 84% sensitivity, 96% specificity, 94% positive
      predictive value, 91% negative predictive value and an overall accuracy of 92%.
      Of the 16 patients with seminal vesicle invasion 14 were identified correctly on
      3D-TRUS. Overall the 3D-TRUS staging sensitivity was 84%, specificity 96%,
      positive predictive value 93%, negative predictive value 91% and accuracy 91%.
      CONCLUSIONS: 3D-TRUS seems to be an accurate technique for staging localized
      prostate cancer. If 3D-TRUS indicates locally advanced disease, the probability
      of capsular perforation or seminal vesicle invasion is very high.

PMID- 17433034
TI  - Clinicopathological features and prognosis of synchronous bilateral renal cell
      carcinoma: an international multicentre experience.
AB  - OBJECTIVE: To present a multicentre experience and the largest cohort to date of
      nonmetastatic (N0M0) synchronous bilateral renal cell carcinoma (RCC), as because
      it is rare the single-institutional experience is limited. PATIENTS AND METHODS:
      We retrospectively studied 10 337 patients from 12 urological centres to identify
      patients with N0M0 synchronous bilateral RCC; the clinicopathological features
      and cancer-specific survival were compared to a cohort treated for N0M0
      unilateral RCC. RESULTS: In all, 153 patients had synchronous bilateral solid
      renal tumours, of whom 135 (88%) had synchronous bilateral RCC, 118 with
      nonmetastatic disease; 91% had nonfamilial bilateral RCC. Bilateral clear cell
      RCC was the major histological subtype (76%), and papillary RCC was the next most
      frequent (19%). Multifocality was found in 54% of bilateral RCCs. Compared with
      unilateral RCC, patients did not differ in Eastern Cooperative Oncology Group
      performance status (ECOG PS) and T classification, but bilateral RCCs were more
      frequently multifocal (54% vs 16%, P < 0.001) and of the papillary subtype (19%
      vs 12%), and less frequently clear cell RCC (76% vs 83%, P = 0.005). For the
      outcome, patients with nonmetastatic synchronous bilateral RCC and unilateral RCC
      had a similar prognosis (P = 0.63); multifocality did not affect survival (P =
      0.60). Multivariate analysis identified ECOG PS, T classification, and Fuhrman
      grade, but not laterality, as independent prognostic factors for cancer-specific
      survival. CONCLUSIONS: Patients with N0M0 synchronous bilateral RCC and N0M0
      unilateral RCC have a similar prognosis. The frequency of a familial history for
      RCC (von Hippel-Lindau disease or familial RCC) was significantly greater in
      bilateral synchronous than in unilateral RCC. The significant pathological
      findings in synchronous bilateral RCC are papillary subtype and multifocality.

PMID- 17433035
TI  - Antitumor effect of TNP-470, an angiogenesis inhibitor, combined with ultrasound
      irradiation for human uterine sarcoma xenografts evaluated using contrast color
      Doppler ultrasound.
AB  - Microvascular endothelial cells, which are recruited by tumors, have become an
      important target in cancer therapy. This study firstly examined the antitumor
      effect of angiogenesis inhibitor combined with ultrasound (US) irradiation for
      human cancer in vivo and evaluated its vascularity using color Doppler US in real
      time with a microbubble US contrast agent. A human uterine sarcoma cell line, FU
      MMT-1, was used in vivo because this tumor is one of the most malignant neoplasms
      of the human solid tumors and it also has a poor response to any of the
      chemotherapeutic agents currently used, as well as to radiotherapy. In angiogenic
      inhibitors, TNP-470 was selected to use in an in vivo study, because this agent
      showed a higher inhibitory effect in tube formation assay in vitro, than that of
      FR118487, or thalidomide. The FU-MMT-1 xenografts in nude mice were treated using
      US at a low-intensity (2.0 w/cm(2), 1MHZ) for 4 min three times per week each
      after the subcutaneous injection of TNP-470 (30 mg/kg), an angiogenesis
      inhibitor, and this treatment was continued for 8 weeks. Either treatment of US
      alone or TNP-470 alone showed a suppression of tumor growth, in comparison to the
      non-treatment group (control), and a significantly enhanced effect was obtained
      using the combined treatment. A reduction in the intratumoral vascularity, which
      was evaluated using both color Doppler and immunohistochemistry, was
      significantly demonstrated using the combined treatment, in comparison to each
      treatment alone, and the control. No side-effect was observed in any mice in the
      combined treatment group. These results suggest that the antitumor effect of TNP
      470 for uterine sarcoma was accelerated by US irradiation in vivo and this
      combination might be a potentially effective for new cancer therapy.

PMID- 17433036
TI  - Novel anticancer agent, benzyldihydroxyoctenone, isolated from Streptomyces sp.
      causes G1 cell cycle arrest and induces apoptosis of HeLa cells.
AB  - In the course of screening for anticancer agents, a novel active compound, F3-2
      5, was isolated from culture broth of Streptomyces sp., KACC91015. Its structure
      was identified using nuclear magnetic resonance, mass spectrometry, and molecular
      modeling experiments, and confirmed by total synthesis. The growth of various
      human cancer cell lines was inhibited in a dose-dependent manner by 0.06-0.48 mM
      F3-2-5 over 24 h. Its IC(50) values were estimated at 37 microM on HeLa, 72
      microM on A549, and 190 microM on HT-29 cells. However, F3-2-5 had no
      antiproliferative effect on normal lymphocytes and normal fibroblasts used as
      controls. Moreover, it affected cell cycle regulation and caused apoptosis of the
      HeLa cells; chromatin condensation and DNA fragmentation were observed in cells
      exposed to 80 microM F3-2-5. Western blot analysis revealed that F3-2-5 inhibited
      phosphorylation of retinoblastoma protein (pRb) and reduced expression of cyclin
      dependent kinase-4 and -6, and cyclin D1 and E, while levels of p53 and
      p21(WAF1/CIP1) increased. Taken together, these findings show that F3-2-5
      inhibits proliferation of HeLa cells by inducing G(1) phase arrest as a
      consequence of inhibition of pRb phosphorylation following up-regulation of
      p21(WAF1/CIP1) and p53. Furthermore, apoptosis in HeLa cells treated with F3-2-5
      was associated with an increase in Bax and p53, leading to release of cytochrome
      c, activation of caspase-3, and -8, and cleavage of poly (ADP-ribose) polymerase.

PMID- 17433037
TI  - Expression of indoleamine 2, 3-dioxygenase and the recruitment of Foxp3
      expressing regulatory T cells in the development and progression of uterine
      cervical cancer.
AB  - Foxp3(+) CD4(+)CD25(+) regulatory T (Treg) cells and immunoregulatory enzyme
      indoleamine 2,3-dioxygenase (IDO) play an important role in immunoregulation.
      Accumulating evidence shows that IDO and Treg cells have potent regulatory
      properties for immune escape in cancer. To evaluate the expression of IDO and the
      localization of Foxp3(+) Treg cells in the development and progression of uterine
      cervical cancer, IDO expression and Foxp3(+) Treg cells in the primary and
      metastatic lesions were studied using immunohistochemistry. IDO expression in
      tumor cells appeared in cervical intraepithelial neoplasia (CIN)-3 of the uterine
      cervix and marked expression in microinvasive cancer cells was observed.
      Interestingly, IDO expression in invasive cancer was confined to the cancer cells
      at the invasive front. Moreover, antigen-presenting cells (APC) at the invasive
      front in primary and metastatic lesions were also expressing IDO. Stromal
      Foxp3(+) Treg cells appeared in CIN-3 and increased in microinvasive and invasive
      cancer. Intraepithelial Foxp3(+) Treg cells were restricted within microinvasive
      and invasive cancer. No significant differences in the proportion of
      Foxp3(+)/CD4(+) in the stroma or epithelium, or between non-metastatic and
      metastatic invasive cancers, were observed in primary lesions of cervical cancer,
      while there was a significant increase (P < 0.005) in the proportion of
      Foxp3(+)/CD4(+) in metastatic lymph nodes compared with non-metastatic lymph
      nodes. Some of the Foxp3(+) Treg cells in metastatic lymph nodes contacted the
      IDO(+) APC. IDO expression at the invasive front of cancer cells and APC, and the
      localization of Foxp3(+) Treg cells in front of cancer tissues, may create a
      network between IDO and Treg for the induction of immune escape.

PMID- 17433038
TI  - Myeloid suppressor cell-associated immune dysfunction in CSA1M fibrosarcoma tumor
      bearing mice.
AB  - CSA1M tumor-bearing mice exhibited a severe immune dysfunction but the underlying
      mechanism remained unclear. In this study, we demonstrated that the myeloid
      suppressor cell (Mac-1(+)Gr-1(+) cells)-(MSC) related T cell immunosuppression in
      this tumor-bearing model. In mice at the late stage of CSA1M tumor-bearing (Late
      TB [8-10 weeks after cell inoculation in male BALB/c mice]), the percentages for
      CD4(+) and CD8(+) T cells decreased but Mac-1(+) cells increased in spleens with
      severe splenomegaly. There was no deficit for concanavalin A-induced CD4(+) and
      CD8(+) T cell proliferation, interferon-gamma (IFN-gamma) and interleukin (IL)-4
      production, but delayed-type hypersensitivity reaction were attenuated. Analysis
      of cytokine production in unfractionated spleen cells showed a significant
      reduction of IFN-gamma and a marked increase of IL-10 and IL-4. In Late-TB mice,
      splenic MSC number intensively accumulated; the mRNA expressions of the signal
      transducer and activator of transcription 1, interferon regulatory factor 1 (IRF
      1), and inducible nitric-oxide synthase (iNOS) were enhanced in MSC; the nitric
      oxide production and arginase enzyme activity increased in MSC as well.
      Furthermore, the concanavalin A-induced T cell proliferation was inhibited in the
      presence of lipopolysaccharide- or IFN-gamma-activated MSC from Late-TB mice,
      which could be reversed by the iNOS specific inhibitor L-NMMA. iNOS seemed to be
      required more than arginase for the suppressive activity of MSC. Taken together,
      our results suggest that the immune dysfunction in tumor-bearing mice might be
      causally associated with the accumulation of MSC and its tumor-favoring property.

PMID- 17433039
TI  - Variant genotypes and haplotypes of the epidermal growth factor gene promoter are
      associated with a decreased risk of gastric cancer in a high-risk Chinese
      population.
AB  - Epidermal growth factor (EGF), a ligand of the EGF receptor, plays a critical
      role in the development of gastric cancer. Genetic variants in its promoter
      region may influence transcription activity and contribute to gastric cancer
      predisposition. To test this hypothesis, we genotyped three EGF promoter
      polymorphisms (G61A, G-1380A, and A-1744G) in a case-control study of 675 gastric
      cancer cases and 704 cancer-free controls. We found that the variant genotypes of
      EGF 61GA/AA were associated with a significantly decreased risk of gastric cancer
      (OR = 0.77, 95% CI = 0.61-0.95), when compared with wild-type homozygote 61GG. In
      the combined analysis with all three loci of EGF, subjects carrying one or more
      variant loci had a significantly decreased risk of gastric cancer in a dose
      response manner (adjusted OR = 0.58, 95% CI = 0.42-0.80 for subjects carrying one
      variant locus and OR = 0.46, 95% CI = 0.32-0.66 for those carrying two to three
      variant loci, respectively; trend test: chi(2) = 16.14, P < 0.001). Compared with
      the most common haplotype GGA, haplotypes AGA, GGG and GAA (each containing one
      variant allele) were associated with 33%, 29% and 34% significantly decreased
      risk of gastric cancer (adjusted OR = 0.67, 95% CI = 0.55-0.82 for AGA; OR =
      0.71, 95% CI = 0.57-0.88 for GGG and OR = 0.66, 95% CI = 0.52-0.84 for GAA,
      respectively). Our findings indicate that variant genotypes and haplotypes of EGF
      promoter might play a role in gastric carcinogenesis.

PMID- 17433040
TI  - Cross-species difference in telomeric function of tankyrase 1.
AB  - Telomeres protect chromosome ends from being recognized as DNA double-strand
      breaks. Telomere shortening, which occurs due to incomplete replication of DNA
      termini, limits the proliferative capacity of human somatic cells and contributes
      as a barrier to carcinogenesis. In most human cancer cells, telomerase maintains
      telomere length whereas TRF1, a telomeric protein, represses telomere access to
      telomerase. Tankyrase 1 is a PARP that dissociates TRF1 from telomeres by
      poly(ADP-ribosyl)ating TRF1. Thus, by reducing TRF1 loading on chromosome ends,
      tankyrase 1 enhances telomere access to telomerase and causes telomere
      elongation. Recent studies of knockout mice suggest that tankyrases may not
      regulate telomere length in mice (Mus musculus). Consistent with this idea is
      that mouse TRF1 has no canonical tankyrase-binding motif. However, the presence
      of such a motif is not a prerequisite to bind tankyrase 1 in certain species.
      Here, we found that, in mice, tankyrase 1 does not bind or poly(ADP-ribosyl)ate
      TRF1. Accordingly, mouse TRF1 was resistant to tankyrase 1-mediated release from
      telomeres. These observations indicate that telomeric function of tankyrase 1 is
      not conserved in mice. We also found that the canonical tankyrase 1-binding motif
      in TRF1 is conserved in several mammals but not in rats. Since mice and rats have
      much higher telomerase activity in their somatic tissues and much longer
      telomeres than those in other mammals, these rodent species might have evolved to
      resign the tankyrase 1-mediated telomere maintenance system. Meanwhile, PARP
      inhibitors induced non-telomeric tankyrase 1 foci in the nuclei, suggesting
      another function of tankyrase 1 at non-telomeric loci.

PMID- 17433041
TI  - Possible role of gadolinium in nephrogenic systemic fibrosis: report of two cases
      and review of the literature.
AB  - Nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy (NSF/NFD) is a
      rare fibrosing disorder that occurs in patients with renal failure. It is
      associated with significant mortality and morbidity. Patients typically present
      with painful or pruritic indurated plaques involving the limbs and trunk, with
      sparing of the face. Severity and rapidity of cutaneous progression correlate
      with poorer prognosis. To date, the management of NSF/NFD remains anecdotal. The
      aetiological link in NSF/NFD is also yet to be confirmed, but renal dysfunction
      seems a common feature. Following recent reports of a possible causative role of
      gadolinium, we present two patients with histologically confirmed NSF/NFD, who
      had exposure to gadolinium-containing contrast agents 1-2 months before onset of
      disease. Severity of renal impairment, lack of immediate dialysis after exposure
      and cumulative dose of gadolinium are possible factors influencing the
      development of NSF/NFD. The process of transmetallation of gadolinium chelates
      may occur in patients with renal impairment, leading to precipitation of free
      gadolinium in the dermis or other organs, causing tissue injury that ultimately
      leads to the clinical manifestations of NSF/NFD. Although the causative role is
      not proven, gadolinium-containing contrast agents should be used only if clearly
      necessary in patients with renal failure.

PMID- 17433042
TI  - The effect of an educational programme to improve the skills of general
      practitioners in diagnosing melanocytic/pigmented lesions.
AB  - BACKGROUND: Skin cancer is a major public health issue in fair-skinned
      populations, and general practitioners (GPs) play an important role in the
      diagnosis and management of this disease. AIMS: To evaluate a self-instructional
      education module with audit and feedback, designed to increase the skills of GPs
      in diagnosing melanocytic lesions and skin cancer. METHODS: This study, conducted
      in Queensland, Australia, included 16 GPs who participated in an 18-month
      programme, comprising a 6-month baseline audit of skin excisions, a 6-month
      educational programme and a 6-month posteducation audit. RESULTS: The overall
      diagnostic accuracy of malignant lesions was 63.2% (95% CI 60.0-66.3) during
      baseline and 64.5% (95% CI 61.1-67.7) posteducation. Significant improvements
      were seen posteducation in the proportion of melanocytic lesions confirmed as
      malignant (6.1% baseline and 13.5% posteducation, chi(2) = 6.6, P = 0.01). GPs
      with < 15 years of practice recorded significantly lower levels of diagnostic
      accuracy at baseline compared with those with >/= 25 years of practice (P =
      0.001). There were no differences in diagnostic skill posteducation according to
      years of practice. CONCLUSIONS: The education programme improved the malignant :
      benign ratio of melanocytic lesions, resulting in a doubling in the number of
      melanomas diagnosed. We found that GPs with less experience benefited most from
      the programme, indicating that tailoring of programmes to individual skills and
      years of practice might be beneficial.

PMID- 17433043
TI  - Aggregatibacter actinomycetemcomitans as indicator for aggressive periodontitis
      by two analysing strategies.
AB  - OBJECTIVE: To compare the subgingival microbiota of aggressive and chronic
      periodontitis (ChP) using single-site and pooled plaque samples. METHODS: In 60
      patients with aggressive or ChP, subgingival plaque was sampled from the four
      deepest pockets using two sterile paper points simultaneously. One paper point
      from each pocket was put in a separate transport vial, the second was pooled with
      the three other paper points of a respective patient. The content of each vial
      was analysed for Aggregatibacter actinomycetemcomitans, Tannerella forsythensis,
      Porphyromonas gingivalis, and Treponema denticola. RESULTS: Pooled plaque samples
      detected higher numbers for all tested pathogens than single-site samples.
      Detection frequencies were similar for both strategies. Using single-site
      samples, A. actinomycetemcomitans detection rate was statistically significantly
      a higher in aggressive than in ChP (p=0.01). A. actinomycetemcomitans was found
      in higher numbers, the other pathogens in lower numbers in aggressive than in
      ChP. Neither presence nor absence of one of the tested bacteria had sufficient
      positive or negative predictive value for aggressive periodontitis. CONCLUSION:
      A. actinomycetemcomitans was detected in higher numbers and frequency in
      aggressive than in ChP. Its detection may confirm the clinical diagnosis and
      influence therapy. As a diagnostic test, its sensitivity and predictive value was
      low.

PMID- 17433044
TI  - Impact of local and systemic factors on the incidence of oral implant failures,
      up to abutment connection.
AB  - AIM: The aim of this retrospective study was to assess the influence of systemic
      and local bone and intra-oral factors on the occurrence of early implant
      failures, i.e. up to the abutment connection. MATERIAL AND METHODS: The surgical
      records of 2004 consecutive patients from the total patient population who had
      been treated in the period 1982-2003 (with a total of 6946 Branemark system
      implants) at the Department of Periodontology of the Catholic University Leuven
      were evaluated. For each patient the medical history was carefully checked. Data
      collection and analysis mainly focused on endogenous factors such as
      hypertension, coagulation problems, osteoporosis, hypo-hyperthyroidy,
      chemotherapy, diabetes type I or II, Crohn's disease, some local factors [e.g.
      bone quality and quantity, implant (length, diameter, location), type of
      edentulism, Periotest value at implant insertion, radiotherapy], smoking habits
      and breach of sterility during surgery. RESULTS: A global failure rate of 3.6%
      was recorded. Osteoporosis, Crohn's disease, smoking habits, implant (length,
      diameter and location) and vicinity with the natural dentition were all
      significantly associated with early implant failures (p<0.05). CONCLUSION: The
      indication for the use of oral implants should sometimes be reconsidered when
      alternative prosthetic treatments are available in the presence of possibly
      interfering systemic or local factors.

PMID- 17433045
TI  - Gene profile in periodontal ligament cells and clones with enamel matrix proteins
      derivative.
AB  - AIM: Evaluate enamel matrix proteins derivative effect on gene expression
      profiles in cultured human periodontal ligament cell population and its clones.
      MATERIAL AND METHODS: Human periodontal ligament (PDL) cells were explanted. Cell
      cloning was performed and clones classified into fibroblastic (FB) and
      mineralized tissue forming (MTF) according to their capacity to express alkaline
      phosphatase and form mineralized tissue. All cell cultures were grown for 7 days,
      with and without enamel proteins added to the medium. Following RNA extraction,
      expression profiling was performed by hybridization with a DNA micro-array.
      Selected genes differed from the control at a significant level smaller than
      p<0.01. RESULTS: Enamel proteins induced major qualitative changes in mRNA
      expression in all PDL cell populations, differently affecting the entire PDL cell
      population and its clones. In the entire PDL cell population, enamel proteins
      significantly enhanced PDL cell function, with a general effect on enhanced cell
      functional metabolism. CONCLUSIONS: Enamel proteins enhanced gene expression
      responsible for protein and mineralized tissue synthesis in the entire PDL
      population. In the MTF clones, nucleic acid metabolism, protein metabolism and
      signal transduction related genes were up-regulated, while in the FB clones, up
      regulated genes were related to cell adhesion, nucleic acid metabolism and signal
      transduction.

PMID- 17433046
TI  - Incidence of tacrolimus-induced gingival overgrowth in the absence of calcium
      channel blockers: a short-term study.
AB  - AIM: The aim of this study was to determine the incidence and severity of
      gingival overgrowth (GO) induced by tacrolimus (Tcr) compared with ciclosporin A
      (CiA) in the absence of calcium channel blockers (CCB) in renal transplant
      recipients. METHODS: Forty patients (20 Tcr and 20 CiA) were evaluated before and
      30 and 90 days after kidney transplantation. Demographic (age, gender) and
      periodontal parameters were recorded for all patients. Patients taking CCB at any
      time during the study were excluded from the investigation. RESULTS: The mean GO
      score was significantly lower (p=0.014) in the Tcr group (6.4%) compared with the
      CiA group (17.9%) after 90 days of immunosuppressive therapy. At 90 days post
      transplant, clinically significant GO was observed in four patients of the CiA
      group and in two of the Tcr group. This difference was not statistically
      significant (0.66). CONCLUSION: No significant difference in the incidence of
      clinically significant GO was observed between the CiA and Tcr groups up to 90
      days of immunosuppressive therapy.

PMID- 17433047
TI  - An important lysine residue in copper/quinone-containing amine oxidases.
AB  - The interaction of xenon with copper/6-hydroxydopa (2,4,5
      trihydroxyphenethylamine) quinone (TPQ) amine oxidases from the plant pulses
      lentil (Lens esculenta) and pea (Pisum sativum) (seedlings), the perennial
      Mediterranean shrub Euphorbia characias (latex), and the mammals cattle (serum)
      and pigs (kidney), were investigated by NMR and optical spectroscopy of the
      aqueous solutions of the enzymes. (129)Xe chemical shift provided evidence of
      xenon binding to one or more cavities of all these enzymes, and optical
      spectroscopy showed that under 10 atm of xenon gas, and in the absence of a
      substrate, the plant enzyme cofactor (TPQ), is converted into its reduced
      semiquinolamine radical. The kinetic parameters of the analyzed plant amine
      oxidases showed that the k(c) value of the xenon-treated enzymes was reduced by
      40%. Moreover, whereas the measured K(m) value for oxygen and for the aromatic
      monoamine benzylamine was shown to be unchanged, the K(m) value for the diamine
      putrescine increased remarkably after the addition of xenon. Under the same
      experimental conditions, the TPQ of bovine serum amine oxidase maintained its
      oxidized form, whereas in pig kidney, the reduced aminoquinol species was formed
      without the radical species. Moreover the k(c) value of the xenon-treated pig
      enzyme in the presence of both benzylamine and cadaverine was shown to be
      dramatically reduced. It is proposed that the lysine residue at the active site
      of amine oxidase could be involved both in the formation of the reduced TPQ and
      in controlling catalytic activity.

PMID- 17433048
TI  - Characterization and expression analysis of the aspartic protease gene family of
      Cynara cardunculus L.
AB  - Cardosin A and cardosin B are two aspartic proteases mainly found in the pistils
      of cardoon Cynara cardunculus L., whose flowers are traditionally used in several
      Mediterranean countries in the manufacture of ewe's cheese. We have been
      characterizing cardosins at the biochemical, structural and molecular levels. In
      this study, we show that the cardoon aspartic proteases are encoded by a
      multigene family. The genes for cardosin A and cardosin B, as well as those for
      two new cardoon aspartic proteases, designated cardosin C and cardosin D, were
      characterized, and their expression in C. cardunculus L. was analyzed by RT-PCR.
      Together with cardosins, a partial clone of the cyprosin B gene was isolated,
      revealing that cardosin and cyprosin genes coexist in the genome of the same
      plant. As a first approach to understanding what dictates the flower-specific
      pattern of cardosin genes, the respective gene 5' regulatory sequences were fused
      with the reporter beta-glucuronidase and introduced into Arabidopsis thaliana. A
      subsequent deletion analysis of the promoter region of the cardosin A gene
      allowed the identification of a region of approximately 500 bp essential for gene
      expression in transgenic flowers. Additionally, the relevance of the leader
      intron of the cardosin A and B genes for gene expression was evaluated. Our data
      showed that the leader intron is essential for cardosin B gene expression in A.
      thaliana. In silico analysis revealed the presence of potential regulatory motifs
      that lay within the aforementioned regions and therefore might be important in
      the regulation of cardosin expression.

PMID- 17433049
TI  - An unspecified clinical syndrome in mentally retarded patients with bilateral
      mesial temporal sclerosis.
AB  - PURPOSE: The association of febrile convulsions and mesial temporal sclerosis
      (MTS) is a well-known phenomenon. However, the effects of mental retardation on
      febrile convulsions and MTS have not been investigated previously. The aim of
      this study is to investigate the relation of mental retardation to febrile
      convulsions especially as febrile status epilepticus and MTS. METHODS: We
      describe three patients who have bilateral mesial temporal sclerosis with mental
      retardation and a history of febrile status epilepticus (FSE), and have
      clinically typical mesial temporal lobe epilepsy (MTLE). RESULTS: The FRSB and
      neuropsychology test revealed executive dysfunction in patients whose bilateral
      MTS had a benign course, which was unexpected. CONCLUSIONS: Febrile status
      epilepticus might have a role in the development of their mental retardation.
      This study also pointed out that MTS might have subtypes as a result of our
      attempts at distinguishing patients with MTS.

PMID- 17433050
TI  - Nonconvulsive status epilepticus in a neurological intensive care unit: profile
      in a developing country.
AB  - PURPOSE: Nonconvulsive status epilepticus (NCSE) is an under-recognized cause of
      altered mental status. There are hardly any reported data on NCSE in developing
      countries. MATERIAL AND METHODS: Prospectively 210 consecutive patients with
      altered mental status admitted to neurological intensive care unit (NICU) of a
      tertiary care center in south India were studied for the frequency of NCSE. All
      patients were evaluated initially with 60-min emergent EEG (EmEEG) and
      subsequently by continuous EEG (cEEG) monitoring. RESULTS: Of the 210 with
      altered mental status admitted to NICU, the diagnosis of NCSE was established in
      22 (10.5%) patients, in 12 (55%) patients with 60-min EmEEG and in 10 (45%) after
      cEEG monitoring for 12 to 48 hours. Of the 22 patients with NCSE, 32% had subtle
      motor phenomena, these were not an initial presenting features, but were apparent
      during cEEG recording. Acute medical or neurologic etiology was the risk factor
      in 68% of patients. Central nervous system (CNS) infections and cortical sino
      venous thrombosis (CSVT), respectively, accounted for 23% and 14% of the
      etiologies. Intravenous midazolam terminated NCSE in 19 patients and valproate in
      2. Of the 15 patients with acute symptomatic NCSE, 4 (18%) had poor prognosis (3
      deaths and one persistent vegetative state). The etiological risk factors in the
      9 (41%) patients with excellent outcome included epilepsy (3), remote symptomatic
      (2), cryptogenic (1), and metabolic and drugs (3). CONCLUSIONS: The frequency of
      NCSE in the current study was comparable with those in prior reports from
      developed countries. CNS infections accounted for about a fifth of the etiology.
      Outcome was excellent in patients with nonacute symptomatic NCSE. Initial 60-min
      EmEEG may be performed in establishing the diagnosis of NCSE, but almost half of
      patients with NCSE will be missed with this approach.

PMID- 17433051
TI  - Risk factors in sudden death in epilepsy (SUDEP): the quest for mechanisms.
AB  - People with epilepsy may die suddenly and unexpectedly without a structural
      pathological cause. Most SUDEP cases are likely to be related to seizures. SUDEP
      incidence varies and is <1:1,000 person-years among prevalent cases in the
      community and approximately 1:250 person years in specialist centres. Case
      control studies identified certain risk factors, some potentially amenable to
      manipulation, including uncontrolled convulsive seizures and factors relating to
      treatment and supervision. Both respiratory and cardiac mechanisms are important.
      The apparent protective effect of lay supervision supports an important role for
      respiratory factors, in part amenable to intervention by simple measures. Whereas
      malignant tachyarrhythmias are rare during seizures, sinus bradycardia/arrest,
      although infrequent, is well documented. Both types of arrhythmias can have a
      genetic basis. This article reviews SUDEP and explores the potential of
      coexisting liability to cardiac arrhythmias as a contributory factor, while
      acknowledging that at present, bridging evidence between cardiac inherited gene
      determinants and SUDEP is lacking.

PMID- 17433052
TI  - The effects of ascorbic acid on penicillin-induced epileptiform activity in rats.
AB  - PURPOSE: Epileptic seizure results from excessive discharge in a population of
      hyperexcitable neurons. A number of studies help to document the effects of
      active oxygen free radical scavengers such as alpha-tocopherol or ascorbic acid
      (vitamin C). In the present study, we examined the effects of ascorbic acid, at
      the six different doses, on penicillin-induced epileptiform activity. METHODS: A
      single microinjection of penicillin (2.5 microl, 500 units, intracortically) into
      the left sensorimotor cortex induced epileptiform activity within 2-5 min,
      progressing to full seizure activity lasting approximately 3-5 h. In the first
      set of experiments, 30 min after penicillin injection, six different doses of
      ascorbic acid (25, 50, 100, 200, 400, or 800 mg/kg) were administered
      intraperitoneally (IP). The other group of animals received the effective dose of
      ascorbic acid (100 mg/kg, IP) for 7 days. Ascorbic acid administration was
      stopped 24 h before penicillin treatment. Another group of rats received the
      effective dose of ascorbic acid (100 mg/kg, IP) 30 min before penicillin
      treatment. In the second set of experiments, the lipid peroxidation (MDA) and
      reduced glutathione (GSH) levels of brain were measured in the control, control +
      ascorbic acid, penicillin, and penicillin + ascorbic acid groups. RESULTS:
      Ascorbic acid, at the low dose (50, 100 mg/kg, 30 min after penicillin
      injection), decreased both the frequency and amplitude of penicillin-induced
      epileptiform activity in rats. Ascorbic acid, at intermediate doses (200, 400
      mg/kg, 30 min after penicillin injection), decreased the frequency of
      epileptiform activity without changing the amplitude. Ascorbic acid, at the
      lowest dose (25 mg/kg) and highest dose (800 mg/kg) (30 min after penicillin
      injection), did not change either the frequency or amplitude of epileptiform
      activity. Ascorbic acid, at the low dose (100 mg/kg) was the most effective dose
      in changing the frequency and amplitude of penicillin-induced epileptiform
      activity. Pretreatment with ascorbic acid (100 mg/kg) 30 min before penicillin
      treatment caused a significant delay in the onset of penicillin-induced
      epileptiform activity. Pretreatment with ascorbic acid (100 mg/kg) for 7 days did
      not change the latency of epileptiform activity. The most effective dose of
      ascorbic acid (100 mg/kg) prevented both the decrease in GSH level and the
      increase in lipid peroxidation level (MDA) occurring after penicillin-induced
      epileptiform activity. CONCLUSIONS: These data indicate that ascorbic acid has
      neuroprotective activity against penicillin-induced epileptiform
      electrocorticogram activity.

PMID- 17433053
TI  - A hypothesis for how non-REM sleep might promote seizures in partial epilepsies:
      a transcranial magnetic stimulation study.
AB  - PURPOSE: To investigate alterations of inhibitory and excitatory cortical
      circuits during non-rapid eye movement (NREM) sleep in drug-naive patients with
      partial epilepsies and sleep-bound seizures only. METHODS: A paired-pulse TMS
      paradigm was used to test intracortical inhibition (ICI) and facilitation (ICF)
      in the hemisphere of the epileptic focus in three untreated patients with
      nonlesional, nongenetic frontal lobe epilepsy in NREM2 (three patients), NREM3/4
      (one patient), and wakefulness (three patients). RESULTS: All three patients
      exhibited a major decrease of ICI in NREM sleep as opposed to the physiological
      enhancement of ICI with the progression of NREM sleep. CONCLUSIONS: Decreased ICI
      might reflect a substrate for the association of epileptic processes with
      thalamocortical networks that propagate sleep. Thus our findings contribute to a
      hypothesis of how NREM sleep could promote seizures.

PMID- 17433054
TI  - Assessment of hairline EEG as a screening tool for nonconvulsive status
      epilepticus.
AB  - PURPOSE: Because of the high incidence of nonconvulsive status epilepticus
      (NCSE), the attraction of a "quick and easy" screening electroencephalogram (EEG)
      is obvious. Previous studies have shown utility of hairline EEG in diagnosing
      epilepsy. However, this technique has not been evaluated as a screening tool for
      NCSE. We wanted to provide proof of principle that a screening hairline EEG has
      sufficient sensitivity to use as a screening tool for diagnosing NCSE. METHODS: A
      total of 120, 2- to 3-min EEG samples of normal and various abnormal digital EEG
      studies were reformatted in three six-channel montages (A, longitudinal bipolar;
      B, referential to ipsilateral ear; C, referential to contralateral ear) that
      mimicked a hairline recording and were interpreted by five neurophysiologists.
      The test data interpretation was compared with the original EEG interpretation.
      RESULTS: Performance was best with montages A and B; 71% and 70.5% of the samples
      were interpreted correctly by using these montages. Only 65% of the samples were
      correctly interpreted by using montage C. With the best montage (A), the
      sensitivities ranged from 91% for normal EEG to 54% for periodic lateralized
      epileptiform discharges (PLEDs). The sensitivity for seizures was only 72%.
      Seizures were frequently misinterpreted as more benign patterns such as normal
      and diffuse slowing. CONCLUSIONS: EEG data reformatted to resemble a hairline EEG
      had low sensitivity for detecting seizures. As a result, we do not recommend
      further pursuit of hairline EEG as a "quick and easy" screening tool for NCSE.

PMID- 17433055
TI  - Effect of focal low-frequency stimulation on amygdala-kindled afterdischarge
      thresholds and seizure profiles in fast- and slow-kindling rat strains.
AB  - PURPOSE: To determine whether low-frequency, 1-Hz sine-wave stimulation (LFS)
      applied to a fully kindled amygdala focus would show antiepileptic properties in
      rats that were either naturally seizure prone (Fast) or seizure resistant (Slow).
      METHODS: Normal twisted and/or "spanning" bipolar electrode configurations were
      implanted in the amygdalae of adult male Fast and Slow rats. In experiment one,
      rats were kindled daily to stage-5 levels through one electrode type until stable
      afterdischarge thresholds (ADTs) were obtained. Next, LFS was applied through the
      kindled electrode, and ADTs were redetermined 1 min later, and daily for a week,
      without reapplying the LFS. In experiment two, a single, normal bipolar kindling
      electrode was implanted in the amygdala and centered between two poles of a
      spanning electrode. After stable kindled ADTs were obtained, LFS was applied to
      the amygdala "area" through the spanning electrode. ADTs were redetermined at the
      kindled electrode as earlier. RESULTS: LFS through the kindling electrode had no
      effect on ADTs 1 min later, but the ADTs increased dramatically 24 h later and
      then slowly returned to baseline over days. In experiment two, LFS applied
      through the nonkindled spanning electrode also showed a small but significant
      threshold elevation at the interposing kindled electrode. Importantly, no obvious
      neuropathology was associated with these LFS treatments. CONCLUSIONS: LFS applied
      directly to the kindled network has significant threshold-elevating properties
      that are less evident when applied to the "general area"; here LFS must be
      delivered through a larger surface area and/or at higher intensity.

PMID- 17433056
TI  - Facial paresis in patients with mesial temporal sclerosis: clinical and
      quantitative MRI-based evidence of widespread disease.
AB  - PURPOSE: To assess the frequency and significance of facial paresis (FP) in a
      well-defined cohort of mesial temporal lobe epilepsy (MTLE) patients. METHODS:
      One hundred consecutive patients with MRI findings consistent with mesial
      temporal sclerosis (MTS) and concordant electroclinical data underwent facial
      motor examination at rest, with voluntary expression, and with spontaneous
      smiling. Hippocampal, amygdaloid, and temporopolar (TP) volumetric measures were
      acquired. Thirty healthy subjects, matched according to age and sex, were taken
      as controls. RESULTS: Central-type FP was found in 46 patients. In 41 (89%) of
      46, it was visualized at rest, with voluntary and emotional expression
      characterizing true facial motor paresis. In 33 (72%) of 46 patients, FP was
      contralateral to the side of MTS. By using a 2-SD cutoff from the mean of normal
      controls, we found reduction in TP volume ipsilateral to MTS in 61% of patients
      with FP and in 33% of those without (p = 0.01). Febrile seizures as initial
      precipitating injury (IPI) were observed in 34% of the patients and were
      classified as complex in 12 (26%) of 46 of those with FP and in five (9%) of 54
      of those without (p = 0.02). The presence of FP was significantly associated with
      a shorter latent period and younger age at onset of habitual seizures, in
      particular, with secondarily generalized tonic-clonic seizures. CONCLUSIONS:
      Facial paresis is a reliable lateralizing sign in MTLE and was associated with
      history of complex febrile seizures as IPI, younger age at onset of disease, and
      atrophy of temporal pole ipsilateral to MTS, indicating more widespread disease.

PMID- 17433057
TI  - Neurologic improvement in a type 3 Gaucher disease patient treated with
      imiglucerase/miglustat combination.
AB  - PURPOSE: Gaucher disease (GD) is an autosomal recessive lysosomal disorder caused
      by a deficiency of glucocerebrosidase. The neurologic manifestations of GD
      patients have to date been refractory to any treatment approach. We present a
      report of a neuronopathic GD patient whose myoclonic epilepsy improved after
      combination therapy with imiglucerase and miglustat. METHODS: In an adult type 3
      GD patient who, despite good visceral and analytic response to ERT, developed
      progressive neurologic deterioration with marked myoclonic epilepsy and dystonia,
      we added miglustat to the enzyme-replacement therapy. RESULTS: After 2 years of
      combined miglustat (200 mg, 3 t.i.d.) and imiglucerase (60 IU/kg every 2 weeks),
      generalized tonic-clonic seizures decreased, speech improved, and the general
      neurologic clinical picture improved markedly. The EEG showed a reduction in
      focal and generalized paroxysmal discharges. No significant adverse effects were
      observed. CONCLUSIONS: Combined imiglucerase and miglustat therapy may be
      beneficial for some neuronopathic forms of GD.

PMID- 17433058
TI  - Ototoxicity after intraperitoneal chemotherapy: a case report.
AB  - Recently, the National Cancer Institute endorsed intraperitoneal (IP) therapy as
      the treatment of choice for optimally debulked epithelial ovarian cancer.
      However, there are no drug regimens that are clearly indicated, and the exact
      method of administration has not been established. Furthermore and most
      importantly, physicians are unaware of what toxicities should be expected with
      their use of IP therapy. We report a recent unanticipated toxicity from IP
      cisplatin therapy and review the literature. A 63-year-old female with optimally
      debulked stage IIIC papillary serous carcinoma of ovary was admitted on
      postoperative day 14 for her first cycle of IP cisplatin. She received a
      cisplatin infusion of 100 mg/m(2). Four days after the cycle, she suffered acute
      onset of bilateral tinnitus and hearing loss (ototoxicity grade 3). Thus, we
      conclude that high-frequency hearing loss remains a potentially serious and
      permanent adverse effect of cisplatin.

PMID- 17433059
TI  - Atypical mucinous metaplasia and intraepithelial neoplasia of the female genital
      tract--a case report and review of the literature.
AB  - Mullerian metaplasia of the female genital tract is usually of limited extent and
      subtype. We describe the replacement of the lining of the entire genital tract
      and much of the overlying pelvic serosa by metaplastic mullerian epithelium, in a
      nulliparous 65-year-old woman with cervical agenesis. She did not have Peutz
      Jeghers syndrome and had not had any form of prior hormonal treatment. The
      metaplastic epithelium extended from the vagina to the serosal surface of the
      pelvic organs. Mucinous epithelium predominated. In addition, there was
      multifocal dysplasia of the metaplastic epithelium; this was most prominent in
      the fallopian tubes where there was marked papillation with cytoarchitectural
      features reminiscent of a borderline mucinous ovarian tumor. Although mullerian
      metaplasia is well recognized at different sites within the female genital tract,
      this highly unusual finding of multiple metaplastic epithelial subtypes and
      dysplasia involving the mucinous metaplastic epithelium along the entire genital
      tract and pelvic serosal surface has not, to the best of our knowledge, been
      reported previously in the absence of Peutz-Jeghers syndrome.

PMID- 17433060
TI  - Association of human leukocyte antigen and T cell message with human
      papillomavirus 16-positive cervical neoplasia in Japanese women.
AB  - To investigate whether an association exists between human leukocyte antigen
      (HLA) haplotype and cervical neoplasia within the Japanese population, we
      analyzed the human papillomavirus (HPV) genotypes, the HLA class I specificities
      and class II alleles, and the T-cell responses in the lesions of patients with
      cervical neoplasia. Eighty-one patients, consisting of 62 cervical
      intraepithelial neoplasia (CIN) lesions and 19 invasive cervical cancers (ICC),
      were examined. The frequencies of HPV infection in the CIN I/II and CIN III/ICC
      groups were 68.0% (17/25) and 80.4% (45/56), respectively. All patients and 138
      local Japanese controls were analyzed for HLA-A, HLA-B, HLA-DRB1, and HLA-DQB1.
      For major histocompatibility complex (MHC) class II HLA-DRB1 alleles, the
      frequency of DRB1*0901 was significantly elevated in HPV 16-positive CIN III/ICC
      patients compared with controls (59.3% versus 29.7%, P = 0.0031, OR = 3.44).
      Similarly for the HLA-DQB1 alleles, a significant increase in the DQB1*03032
      frequency was observed in HPV 16-positive CIN III/ICC patients compared with
      controls (59.3% versus 28.3%, P = 0.0018, OR = 3.69). In the analysis of the T
      cell responses in the lesions, Fas ligand was detected at a decreased frequency
      in HPV 16-positive CIN III/ICC patients with the HLA-DRB1*0901-DQB1*03032
      haplotype. The presence of helper T cell-specific messenger RNAs in the cervical
      lesions supports an association among MHC class II, helper T cells, the immune
      response to HPV, and the development of cervical carcinoma. Accordingly, a
      specific MHC class II haplotype, DRB1*0901-DQB1*03032, may be a risk factor for
      cervical carcinoma in the Japanese population.

PMID- 17433061
TI  - Design of a bio-mathematical prediction model using serum tumor markers and
      immunohistochemistry in peritoneal carcinomatosis with ovarian involvement: a
      pilot study.
AB  - The diagnosis of disseminated intra-abdominal malignancy in women with ovarian
      involvement can be problematic. Whilst both blood tumor markers and use of
      immunohistochemical staining on tissue can help decide the origin of the tumor,
      this is done separately. This study looked at the blood and tissue marker
      profiles of 198 cases of disseminated malignancy to construct a model, which may
      help to determine tumor origin. The original histology material from 198 cases of
      disseminated intra-abdominal epithelial malignancy were reviewed, blind, and
      reassessed as to the likely site of origin. These cases had immunohistochemical
      (IHC) staining for cytokeratins (CK) 7 and 20, carcinoembryonic antigen (CEA) and
      CA125. Blood values for CEA and CA125 were also known at diagnosis. The
      histologic types of the tumors in this pilot study were of ovarian type
      morphologically in 130 cases (65.7%), nonovarian in 32 (16.1%), and not assigned
      in 36 cases (18.2%). The majority of the nonovarian cases were of mucinous type
      or too poorly differentiated to classify. Analysis showed an overall sensitivity
      and specificity of 93% and 69%, and positive predictive and negative predictive
      value of 92% and 71%, respectively, for a diagnosis of ovarian vs nonovarian
      origin using histology alone vs histology and IHC. Use of an ordinal regression
      developed a model which uses tissue staining for CK 7 and CEA along with blood
      levels of CEA to help determine the site of tumor origin.

PMID- 17433062
TI  - Radical hysterectomy for cervical cancer amongst women infected with the human
      immunodeficiency virus.
AB  - Invasive cervical cancer and human immunodeficiency virus (HIV) infection are an
      epidemic in South Africa. Most HIV-infected patients with cervical cancer present
      with late-stage disease. Whilst the literature describes the outcome of such
      women with preneoplastic cervical lesions, the management of early-stage invasive
      cervical cancer and HIV is lacking. We present our experience with such patients.

PMID- 17433063
TI  - Accuracy of magnetic imaging of inguinofemoral lymph nodes in vulval cancer.

PMID- 17433064
TI  - Pattern and clinical predictors of lymph node metastases in epithelial ovarian
      cancer.
AB  - Para-aortic lymphadenectomy is part of staging in early epithelial ovarian cancer
      (EOC) and could be part of therapy in advanced EOC. However, only a minority of
      patients receive therapy according to guidelines or have attendance to a
      specialized unit. We analyzed pattern of lymphatic spread of EOC and evaluated if
      clinical factors and intraoperative findings reliably could predict lymph node
      involvement, in order to evaluate if patients could be identified in whom
      lymphadenectomy could be omitted and who should not be referred to a center with
      capacity of performing extensive gynecological operations. Retrospective analysis
      was carried out of all patients with EOC who had systematic pelvic and para
      aortic lymphadenectomy during primary cytoreductive surgery. One hundred ninety
      five patients underwent systematic pelvic and para-aortic lymphadenectomy.
      Histologic lymph node metastases were found in 53%. The highest frequency was
      found in the upper left para-aortic region (32% of all patients) and between vena
      cava inferior and abdominal aorta (36%). Neither intraoperative clinical
      diagnosis nor frozen section of pelvic nodes could reliably predict para-aortic
      lymph node metastasis. The pathologic diagnosis of the pelvic nodes, if used as
      diagnostic tool for para-aortic lymph nodes, showed a sensitivity of only 50% in
      ovarian cancer confined to the pelvis and 73% in more advanced disease. We could
      not detect any intraoperative tool that could reliably predict pathologic status
      of para-aortic lymph nodes. Systematic pelvic and para-aortic lymphadenectomy
      remains part of staging in EOC. Patients with EOC should be offered the
      opportunity to receive state-of-the-art treatment including surgery.

PMID- 17433065
TI  - Prognostic impact of KI67, p53, human epithelial growth factor receptor 2,
      topoisomerase IIalpha, epidermal growth factor receptor, and nm23 expression of
      ovarian carcinomas and disseminated tumor cells in the bone marrow.
AB  - Examination of tumor biological factors for prognostic and predictive indicators
      is not part of routine testing in ovarian cancer. As in other tumors, the
      detection of hematogenous tumor spread could help to estimate the risk of
      metastatic disease. We examined the expression of p53, KI67, topoisomerase
      IIalpha (Top IIa), epidermal growth factor receptor (EGFR), human epithelial
      growth factor receptor 2 (HER2) and nm23 in tumor tissues from 90 patients with
      ovarian cancer. All underwent bone marrow (BM) aspiration and screening for
      disseminated tumor cells in the bone marrow (DTC-BM) at primary diagnosis. BM
      aspiration, cytospin preparation, and immunocytochemical staining with the
      anticytokeratin antibody (A45-B/B3) were done following a standardized protocol.
      The expression of p53, KI67, Top IIa, EGFR, HER2, and nm23 was evaluated by
      immunohistochemistry on paraffin-embedded tissue samples and classified by
      percentage of stained cells or immunoreactive score (IRS). The prognostic impact
      of the individual factors together with standard histologic parameters was
      calculated by univariate and multivariate analyses. Expression rates for HER2
      (2+/3+: 34.5%), KI67 (median 30%), p53 (median IRS 5), and Top IIa (median IRS 4)
      were relatively high, whereas nm23 (median IRS 2) and EGFR (IRS 0: 61%) showed
      weak staining. In 21/90 patients (23.3%), DTC-BM (>/=1/2 x 10(6) cells) could be
      detected. The presence of DTC-BM was inversely related to nodal status (P = .015)
      but not to the other factors examined. Tumor stage (P = .02), lymph node
      involvement (P = .003), grade (P = .046), postoperative tumor residue (P < .001),
      peritoneal seeding (P = .02), and KI67 (P = .046) significantly correlated with
      overall survival (OS) after a median observation time of 28 months (2-105). The
      finding of ascites was borderline significant (P = .050). The presence of DTC-BM
      (P = .04) and KI67 positivity (P = .02) predicted reduced distant disease-free
      survival. By multivariate analysis, postoperative tumor residue remained an
      independent factor for OS (P = .02, relative risk = 4.6). As a primarily
      locoregional disease, tumor stage and postoperative tumor residue are the main
      determinants of prognosis in patients with ovarian cancer. However, even in
      advanced stages, examination of tumor biological factors could help to stratify
      subgroups of patients and establish targeted therapies.

PMID- 17433066
TI  - Preservation of pregnancy in a patient with advanced ovarian cancer at 20 weeks
      of gestation: case report and literature review.
AB  - To report a case of FIGO stage III papillary serous carcinoma of ovary, diagnosed
      during pregnancy at 20 weeks of gestation and treated with unilateral salpingo
      oophorectomy and surgical staging, then initial combination chemotherapy while
      preserving the pregnancy. The patient underwent cesarean section at 35 weeks
      after four courses of taxol plus carboplatin. She delivered a healthy baby. After
      that total hysterectomy, omentectomy, pelvic and para-aortic lymphadenectomies
      were carried out. The surgical resection was complete and no macroscopic residual
      diseases were seen. During histologic examination, traces of resistant disease
      were found. The patient underwent three postoperative courses of chemotherapy
      (carboplatin plus paclitaxel regimen). After 6 months follow-up, the patient
      remained in complete remission and the child's development was normal.
      Combination chemotherapy during pregnancy with preservation of the fetus could be
      considered, and should be discussed with caution in case of epithelial ovarian
      cancer diagnosed during the second trimester of the pregnancy.

PMID- 17433067
TI  - Galectin-3 may contribute to Cisplatin resistance in clear cell carcinoma of the
      ovary.
AB  - Our previous findings suggested that lower cell proliferation of clear cell
      carcinoma (CCC) of the ovary may contribute to its resistance to chemotherapy. We
      conducted the present study to find the gene that regulates cell proliferation of
      CCC and to elucidate whether it contributes to cisplatin (CDDP) resistance.
      Complementary DNA microarray analysis revealed that the gene expression level of
      galectin-3 of CCC cell lines (KK, RMG-I, HAC-2) was over threefold higher than
      that of ovarian serous adenocarcinoma (SAC) cell lines (HRA, KF). S-phase
      fraction increased after knocking down galectin-3 using small interfering RNA in
      RMG-I, KK, and HAC-2 cells. The protein expression of p27 decreased after
      knocking down galectin-3. CDDP-induced apoptosis was increased after knocking
      down galectin-3, and this cytotoxic effect was canceled by roscovitine.
      Immunohistochemical staining showed that galectin-3 expression in tumors of 20
      CCC was significantly more frequent than that of 20 SAC (70.0% vs 15.0%, P =
      0.0004). The present study showed that the expression of galectin-3 in CCC might
      contribute to its lower cell proliferation and lead to CDDP resistance.

PMID- 17433068
TI  - A comparative study of voltage-gated sodium channels in the Insecta: implications
      for pyrethroid resistance in Anopheline and other Neopteran species.
AB  - We report the complete cDNA sequence of the Anopheles gambiae voltage-gated
      sodium channel (VGSC) alpha-subunit isolated from mature adult mosquitoes. The
      genomic DNA contains 35 deduced exons with a predicted translation of <or= 2139
      amino acid cDNAs. The transcription of the gene is, however, complex, alternate
      splicing being evident for at least five optional exons (or exon segments) and
      two sets of mutually exclusive exons. Overall gene organization was also compared
      with that of other VGSCs within the Insecta. Several insecticides used in
      mosquito control (including DDT and synthetic pyrethroids) target the VGSC.
      Isolation of the sodium channel cDNA for An. gambiae: (1) allows prediction of
      likely single nucleotide polymorphisms that may arise at residue L1014 to cause
      resistance to insecticides; (2) defines An. gambiae exon usage in key areas of
      the VGSC protein that are known (from previous studies in a range of different
      pest species) to have roles in altering insecticide susceptibility and in
      generating resistance; and (3) is a critical first step towards development of
      refined malarial control strategies and of new diagnostics for resistance
      monitoring.

PMID- 17433069
TI  - Isolation and extreme sex-specific expression of cytochrome P450 genes in the
      bark beetle, Ips paraconfusus, following feeding on the phloem of host ponderosa
      pine, Pinus ponderosa.
AB  - We have identified cDNAs and characterized the expression of 13 novel cytochrome
      P450 genes of potential importance in host colonization and reproduction by the
      California fivespined ips, Ips paraconfusus. Twelve are of the Cyp4 family and
      one is of the Cyp9 family. Following feeding on host Pinus ponderosa phloem, bark
      beetle transcript levels of several of the Cyp4 genes increased or decreased in
      males only or in both sexes. In one instance (IparaCyp4A5) transcript accumulated
      significantly in females, but declined significantly in males. The Cyp9 gene
      (Cyp9T1) transcript levels in males were > 85 000 x higher at 8 h and > 25 000 x
      higher at 24 h after feeding compared with nonfed controls. Transcript levels in
      females were approximately 150 x higher at 24 h compared with nonfed controls.
      Cyp4G27 transcript was present constitutively regardless of sex or feeding and
      served as a better housekeeping gene than beta-actin or 18S rRNA for the real
      time TaqMan polymerase chain reaction analysis. The expression patterns of
      Cyp4AY1, Cyp4BG1, and, especially, Cyp9T1 in males suggest roles for these genes
      in male-specific aggregation pheromone production. The differential transcript
      accumulation patterns of these bark beetle P450s provide insight into ecological
      interactions of I. paraconfusus with its host pines.

PMID- 17433070
TI  - Identification of two sterol carrier protein-2 like genes in the yellow fever
      mosquito, Aedes aegypti.
AB  - Two genes encoding sterol carrier protein-2 like proteins are identified from
      fourth instar cDNAs of the yellow fever mosquito, Aedes aegypti. The predicted
      AeSCP-2like1 (AeSCP-2L1) and AeSCP-2like2 (AeSCP-2L2) proteins are small, acidic
      and lacking the peroxisomal targeting sequence at the C-termini. Purified
      recombinant AeSCP-2L1 and -2L2 bind to cholesterol with a Kd of 5.4 x 10(-6) M
      and 2.6 x 10(-6) M, respectively. The Kd values of AeSCP-2L1 and -2L2 to palmitic
      acid are 3.7 x 10(-7) M and 2.6 x 10(-7) M, respectively. Both genes are
      expressed predominantly in gut tissues. The transcripts of the AeSCP-2L1 gene are
      only detected in larval stages, whereas AeSCP-2L2 is expressed in larval and
      adult stages. AeSCP-2L2 transcription increases within 5 h after a bloodmeal and
      stays at high levels during vitellogenesis. In in vitro larval gut tissue
      cultures, AeSCP-2L1 transcripts were increased in the presence of juvenile
      hormone III, whereas AeSCP-2L2 mRNA levels increased in the presence 20
      hydroxylecdysone. The results suggest that transcription of AeSCP-2L1 and -2L2
      genes are regulated differently through the mosquito life cycle.

PMID- 17433071
TI  - Transcriptional analysis of insecticide resistance in Anopheles stephensi using
      cross-species microarray hybridization.
AB  - A large scale microarray (20k MMC1) from the African malaria vector Anopheles
      gambiae was used to monitor gene expression in insecticide resistant and
      susceptible strains of the Asian mosquito Anopheles stephensi. Heterologous
      hybridization at slightly reduced stringency yielded approximately 7000
      significant signals. Thirty-six putative genes were differentially transcribed
      between the pyrethroid-resistant (DUB-R) and the susceptible (BEECH) strains. The
      expression profiles of selected transcripts were verified by real-time PCR. A
      gene putatively involved in the thickening of the adult cuticle showed the most
      striking up-regulation in DUB-R. A more specialized microarray containing 231 An.
      gambiae genes putatively involved in insecticide detoxification was used to
      further analyse classical insecticide resistance genes. Three glutathione S
      transferase (GST) transcripts, one esterase and a cytochrome P450 were up
      regulated in the resistant strain, while two peroxidases were down-regulated.

PMID- 17433072
TI  - Cowpea bruchid Callosobruchus maculatus counteracts dietary protease inhibitors
      by modulating propeptides of major digestive enzymes.
AB  - Cowpea bruchids, when challenged by consumption of the soybean cysteine protease
      inhibitor scN, reconfigure expression of their major CmCP digestive proteases and
      resume normal feeding and development. Previous evidence indicated that insects
      selectively induced CmCPs from subfamily B, that were more efficient in
      autoprocessing and possessed not only higher proteolytic, but also scN-degrading
      activities. In contrast, dietary scN only marginally up-regulated genes from the
      more predominant CmCP subfamily A that were inferior to subfamily B. To gain
      further molecular insight into this adaptive adjustment, we performed domain
      swapping between the two respective subfamily members B1 and A16, the latter
      unable to autoprocess or degrade scN even after intermolecular processing.
      Swapping the propeptides did not qualitatively alter autoprocessing in either
      protease isoform. Incorporation of either the N- (pAmBA) or C-terminal (pAmAB)
      mature B1 segment into A16, however, was sufficient to prime autoprocessing of
      A16 to its mature form. Further, the swap at the N-terminal mature A16 protein
      region (pAmBA) resulted in four amino acid changes. Replacement of these amino
      acid residues by the corresponding B1 residues, singly and pair-wise, revealed
      that autoprocessing activation in pAmBA resulted from cumulative and/or
      coordinated individual effects. Bacterially expressed isolated propeptides (pA16
      and pB1) differed in their ability to inhibit mature B1 enzyme. Lower inhibitory
      activity in pB1 is likely attributable to its lack of protein stability. This
      instability in the cleaved propeptide is necessary, although insufficient by
      itself, for scN-degradation by the mature B1 enzyme. Taken together, cowpea
      bruchids modulate proteolysis of their digestive enzymes by controlling proCmCP
      cleavage and propeptide stability, which explains at least in part the plasticity
      cowpea bruchids demonstrate in response to protease inhibitors.

PMID- 17433073
TI  - Characterization of phosphatase and tensin homolog expression in the mosquito
      Aedes aegypti: six splice variants with developmental and tissue specificity.
AB  - Phosphatase and tensin homologue (PTEN), an inhibitor of insulin signalling, was
      characterized in Aedes aegypti. Surprisingly, six splice variants were
      identified: three with alternative terminal exons (AaegPTEN2 : 3 : 6) and three
      formed by intron retention (AaegPTEN1 : 4 : 5). All variants encoded active
      phosphatase domains. Variants with alternative terminal exons also encoded C2 and
      COOH-domains, and AaegPTEN6 encoded a PDZ binding motif. These three variants
      also had unique expression patterns. AaegPTEN2 was expressed primarily in the
      ovary. AaegPTEN3 was predominant in heads and midguts, and throughout
      development, except early embryogenesis. AaegPTEN6 was expressed in fat body,
      ovaries, and throughout development. Intron retention variants were weakly
      expressed in most samples. These expression patterns suggest that AaegPTEN
      variants play unique roles in regulating insulin's pleiotropic effects.

PMID- 17433074
TI  - CD59 or C3 are not requred for angiotensin II-dependent hypertension or
      hypertrophy in mice.
AB  - Complement is a major pro-inflammatory innate immune system whose serum activity
      correlates with systolic blood pressure in humans. To date, no studies using in
      vivo models have directly examined the role of individual complement components
      in regulating vessel function, hypertension and cardiac hypertrophy. Herein, in
      vivo responses to angiotensin (ang) II were characterized in mice deficient in
      CD59a or C3. CD59a(-/-) mice had slightly but significantly elevated systolic
      blood pressure (107.2 +/- 1.7 mmHg versus 113.8 +/- 1.31 mmHg, P < 0.01, for wild
      type and CD59a(-/-), respectively). Aortic rings from CD59a(-/-) mice showed
      significantly less platelet endothelial cell adhesion molecule-1 (PECAM-1)
      expression, with elevated deposition of membrane attack complex. However,
      acetylcholine- and sodium nitroprusside-dependent dilatation, plasma
      nitrate/nitrite and aortic cyclic guanosine monophosphate levels were unchanged
      from wild-type. Also, in vivo infusion with either ang II or noradrenaline caused
      similar hypertension and vascular hypertrophy to wild-type. Mice deficient in C3
      had similar basal blood pressure to wild type and showed no differences in
      hypertension or hypertrophy responses to in vivo infusion with ang II. These data
      indicate that CD59a deficiency is associated with some vascular alterations that
      may represent early damage occurring as a result of increased complement attack.
      However, a direct role for CD59a or C3 in modulating development of ang II
      dependent hypertension or hypertrophy in vivo is excluded and we suggest caution
      in development of complement intervention strategies for hypertension and heart
      failure.

PMID- 17433075
TI  - Increased levels of interferon-gamma primed by culture filtrate proteins antigen
      and CpG-ODN immunization do not confer significant protection against
      Mycobacterium tuberculosis infection.
AB  - The results of various animal model studies of tuberculosis (TB) suggest that
      culture filtrate proteins (CFPs), which are antigens secreted by Mycobacterium
      tuberculosis, are largely responsible for improvements in TB vaccines. The great
      obstacle to developing protein subunit vaccines is that adjuvants are required in
      order to stimulate relevant protective immune responses. Acting as immune
      adjuvants, CpG-oligodeoxynucleotides (CpG-ODNs) promote the activation of Th1
      cells and of pro-inflammatory cytokines. To evaluate the adjuvant role of CpG
      ODNs in conferring enhanced immunogenic capacity and protection against M.
      tuberculosis, we immunized mice with CFP antigen combined with synthetic CpG-ODNs
      (CFP/CpG) or with incomplete Freund's adjuvant (IFA) (CFP/IFA). Immunization with
      CFP/CpG induced a T helper 1 (Th1)-biased response accompanied by a higher
      immunoglobulin G2a (IgG2a) antibody/IgG1 antibody ratio, elevated production of
      interferon-gamma (IFN-gamma) by spleen cells and in lungs. However, CFP/IFA
      immunized mice presented higher levels of IgG1 antibodies, as well as increased
      production of IFN-gamma, interleukin (IL)-5, and IL-10 by spleen cells, together
      with lower levels of IFN-gamma in the lungs. Despite the stronger Th1 response
      seen in both groups, believed to be necessary for protection against TB, only
      mice immunized with CFP/IFA were protected after M. tuberculosis infection. Lung
      histology revealed that lung parenchyma were better preserved in CFP/IFA
      immunized mice, which also presented intense lymphocyte recruitment to the
      lesion, whereas CFP/CpG-immunized mice presented severe pulmonary injury
      accompanied by necrosis. Based on the data presented, we discuss the widely
      accepted paradigm that high levels of IFN-gamma are directly correlated with
      protection against experimental TB.

PMID- 17433076
TI  - Granulocyte-macrophage colony-stimulating factor drives monocytes to CD14low
      CD83+ DCSIGN- interleukin-10-producing myeloid cells with differential effects on
      T-cell subsets.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) has long been found to
      have growth-promoting effects on multipotent haematopoietic lineages,
      specifically granulocytes and macrophages. GM-CSF combined with interleukin-4 (IL
      4) drives monocytes to become myeloid dendritic cells (mDCs) in vitro. We report
      that culturing human monocytes with GM-CSF alone generates myeloid cells (GM
      Mono) that have lower expression of CD14 than monocytes and that fail to express
      DC-SIGN. GM-Monos, however, express CD83 and the transcription factor PU.1,
      although at a lower level than the conventional mDCs generated in the presence of
      GM-CSF and IL-4. On stimulation with tumour necrosis factor-alpha, interferon
      gamma and anti-CD40 monoclonal antibody, the GM-Monos predominantly produced IL
      10 but were less efficient in IL-12 production. In a primary allogeneic mixed
      lymphocyte reaction, GM-Monos induced hyporesponsiveness and IL-10-biased
      cytokine production in CD4(+) T cells. In fresh mixed lymphocyte reaction, GM
      Monos inhibited conventional mDC-induced allogeneic CD4(+) T-cell proliferation.
      GM-Mono-induced inhibition of allogeneic CD4(+) T-cell proliferation was
      partially attributed to IL-10. Interestingly, GM-Monos neither induced
      hyporesponsiveness in allogeneic CD8(+) T cells nor inhibited conventional mDC
      induced allogeneic CD8(+) T-cell proliferation. Taken together, we characterize
      monocyte-derived CD14(low) CD83(+) cells generated by GM-CSF that can induce
      tolerance or stimulation of T cells depending on T-cell subsets.

PMID- 17433077
TI  - Disruption of Rxra gene in thymocytes and T lymphocytes modestly alters
      lymphocyte frequencies, proliferation, survival and T helper type 1/type 2
      balance.
AB  - Retinoid X receptor (RXR) agonists, including the vitamin A metabolite 9-cis
      retinoic acid, decrease T-lymphocyte apoptosis and promote T helper type 2 (Th2)
      development ex vivo. To examine the in vivo role of RXR-alpha in T-lymphocyte
      development and function, we disrupted the Rxra gene in thymocytes and T
      lymphocytes using cyclization recombinase (Cre)-loxP-mediated excision of Rxra
      exon 4. Expression of Cre was targeted to these cells using the Lck promoter.
      Successful disruption of exon 4 was seen in thymus and T lymphocytes. Mice were
      healthy and the thymus, spleen and lymph nodes appeared normal. However, knockout
      mice had a lower percentage of double-positive (CD4(+) CD8(+)) and a higher
      percentage of double-negative thymocytes than wild-type mice. The percentage of
      splenic B lymphocytes was lower in unimmunized and ovalbumin-immunized knockout
      mice and the percentage of T lymphocytes was lower in immunized knockout mice. Ex
      vivo proliferation was decreased and apoptosis was increased in T lymphocytes
      from knockout mice. Memory CD4(+) T lymphocytes from knockout mice produced more
      interferon-gamma and interleukin-2 (IL-2) and less IL-5 and IL-10 than memory
      cells from wild-type mice, indicating a Th1 bias in vivo. However, Rxra
      disruption did not similarly bias ex vivo differentiation of naive CD4(+) T
      lymphocytes, nor did Rxra disruption alter the serum immunoglobulin
      G1/immunoglobulin G2a response to immunization. In summary, disruption of Rxra
      altered the percentages of T and B lymphocytes, produced a Th1 bias in vivo, and
      altered T-lymphocyte proliferation and apoptosis ex vivo. These differences were
      modest in magnitude and their impact on disease resistance is yet to be examined.

PMID- 17433078
TI  - Triacylated lipoproteins derived from Mycoplasma pneumoniae activate nuclear
      factor-kappaB through toll-like receptors 1 and 2.
AB  - Pathogenesis of Mycoplasma pneumoniae infection is considered to be in part
      attributed to excessive immune responses. Recently, a mycoplasma lipoprotein has
      been shown to induce nuclear factor kappaB (NF-kappaB) activation through toll
      like receptor 1 (TLR1), TLR2 and TLR6. In this study, we examined the ability of
      lipoproteins from M. pneumoniae to activate NF-kappaB through TLR1- and TLR2
      dependent, but TLR6-independent, pathways, and the active components responsible
      for the NF-kappaB activation through the TLR6-independent pathway were
      identified. The active lipoproteins were found to be MPN611 and MPN162 of M.
      pneumoniae (designated N-ALP1 and N-ALP2, respectively). Purified N-ALP1 and N
      ALP2 from M. pneumoniae and triacylated partial synthetic lipopeptides of N-ALP1
      and N-ALP2 augmented the levels of NF-kappaB induction through TLR1- and TLR2
      dependent pathways, whereas diacylated partial synthetic lipopeptides of N-ALP1
      and N-ALP2 activated NF-kappaB through TLR1-, TLR2- and TLR6-dependent pathways.
      These data suggest that N-ALP1 and N-ALP2 would be triacylated lipoproteins. The
      activity of N-ALP1 and N-ALP2 was decreased with a pretreatment of lipoprotein
      lipase, and partially decreased by protease treatment, indicating that the lipid
      moiety of N-ALP1 and N-ALP2 is critical for the NF-kappaB activation. Thus,
      triacylated lipoproteins derived from M. pneumoniae might activate NF-kappaB
      through TLR1 and TLR2, but not TLR6.

PMID- 17433080
TI  - Pulsus alternans in English cocker spaniels with dilated cardiomyopathy.
AB  - OBJECTIVES: To report the clinical findings associated with pulsus alternans in
      English cocker spaniels with dilated cardiomyopathy and to review the phenomenon
      of mechanical alternans, usually found in patients with severe left ventricular
      systolic dysfunction. METHODS: The case records of 10 English cocker spaniels
      with dilated cardiomyopathy and pulsus alternans were reviewed. All dogs had been
      referred in moderate to severe congestive heart failure. Pulsus alternans was
      clinically recognised by palpation of a regular alternation of femoral pulse
      amplitude and confirmed by echocardiography in all cases. Pulsus alternans was an
      intermittent finding in all 10 dogs. RESULTS: Phonocardiographic recordings were
      obtained in three dogs to document variation in the intensity of the heart
      sounds, with one case exhibiting absence of the second heart sound in alternate
      beats. M-mode echocardiography performed in all dogs showed alternation of the
      pattern of mitral valve diastolic motion. Doppler echocardiography showed marked
      alternation in stroke volume in the aortic outflow in all cases. It also showed
      alternation in mitral regurgitation and in the velocity of early ventricular
      filling. CLINICAL SIGNIFICANCE: Pulsus alternans may be more prevalent in English
      cocker spaniels than in other breeds, and because of its intermittent nature, its
      incidence may be higher than that previously reported. It has diagnostic
      relevance as it usually indicates severe myocardial depression. Echocardiography
      allows non-invasive detection of mechanical alternans and provides further
      insights into its pathophysiology and clinical significance.

PMID- 17433079
TI  - Ureteral sarcoma in a dog.
AB  - A ureteral sarcoma was diagnosed in a nine-year-old Weimaraner dog with gross
      haematuria, severe unilateral hydronephrosis, and hydroureter. Treatment
      consisted of unilateral nephrectomy and ureterectomy. This case was compared with
      14 other ureteral tumours reported in the veterinary literature. Only three
      previous reports concerned a malignant ureteral tumour. Urinary tract neoplasms
      mainly involve the bladder and the kidney, and more rarely the urethra. The
      purpose of this paper is to report a rare case of malignant ureteral tumour in a
      dog.

PMID- 17433081
TI  - Journey into the realm of requests for help presented to sexual medicine
      specialists: introducing male sexual distress.
AB  - INTRODUCTION: The recent availability of noninvasive pharmacological remedies for
      male sexual function triggered an exponential increase in the number of men
      requesting help in the sexuality area. AIM: The Italian Society of Andrology
      explored requests for help, not included in formerly established clinical
      categories of sexual medicine. METHODS: A central board of 67 andrologists
      identified new areas of requests for help, instrumental for a web-based
      questionnaire, forwarded to 912 members of the Italian Society of Andrology.
      Results were submitted to an independent consensus development panel. MAIN
      OUTCOME MEASURES: A questionnaire response rate of 30.8% was considered
      acceptable according to standard response rates of medical specialist samples.
      RESULTS: The Central Board interaction identified two new domains of requests for
      help: sexual distress and unconventional requests for pro-erectile medications.
      Web-based questionnaire results suggested that such domains account for 29% and
      9% respectively of all requests for help already presented by male patients at
      sexual medicine clinics. The Independent Consensus Development Panel issued a
      final consensus document; herewith, the statement defining male sexual distress:
      A non-transitory condition and/or feeling of inadequacy such as to impair "sexual
      health" (WHO working definition). Inadequacy can originate both from
      physiological modifications of male sexual functions, and from diseases,
      dysfunctions, dysfunctional symptoms and dysmorphisms, both of andrological and
      non-andrological origin, which do not relate to "erectile dysfunction" (NIH
      Consensus Development Panel definition), but that might also induce erectile
      dysfunction. Sexual Distress can lead to a request for help which needs to be
      acknowledged. CONCLUSION: The Italian Society of Andrology identified two new
      areas of requests for help concerning male sexual issues: sexual distress and
      unconventional requests for pro-erectile medications. These domains, which do not
      represent new diseases, nonetheless induce the sufferers to seek help and,
      accordingly, need to be acknowledged.

PMID- 17433082
TI  - Antisense and short hairpin RNA (shRNA) constructs targeting PIN (Protein
      Inhibitor of NOS) ameliorate aging-related erectile dysfunction in the rat.
AB  - INTRODUCTION: Over-expression of penile neuronal nitric oxide synthase (PnNOS)
      from a plasmid ameliorates aging-related erectile dysfunction (ED), whereas over
      expression of the protein inhibitor of NOS (PIN), that binds to nNOS, increases
      ED. AIM: To improve this form of gene therapy for ED by comparing the electrical
      field response of short hairpin RNA (shRNA) for PIN with that of antisense PIN
      RNA. MAIN OUTCOME MEASURE: Both shRNA and antisense RNA gene therapy vectors
      increased intracavernosal pressure in aged rats. METHODS: PIN small interfering
      RNA (siRNA), and plasmid constructs for cytomegalovirus promoter plasmid vector
      (pCMV-PIN), pCMV-PIN antisense RNA, pSilencer2.1-U6-PIN-shRNA; and pSilencer2.1
      U6-randomer-shRNA were prepared and validated by transfection into HEK293 cells,
      determining the effects on PIN expression by Western blot. Plasmid constructs
      were then injected, followed by electroporation, into the penile corpora
      cavernosa of aged (20-month-old) Fisher 344 rats and, 1 month later, the erectile
      response was measured by intracavernosal pressure increase following electrical
      field stimulation (EFS) of the cavernosal nerve. PIN was estimated in penile
      tissue by Western blot and real-time reverse transcriptase-polymerase chain
      reaction. Cyclic guanosine monophosphate (cGMP) measurements were conducted by
      competitive enzyme immunoassay (EIA). Immunohistofluorescence detected PIN in
      corporal tissue sections. RESULTS: In cell culture, PIN siRNA and plasmid
      expressed pU6-PIN-shRNA effectively reduced PIN expression from pCMV-PIN.
      pSilencer2.1-U6-PIN-shRNA corrected the impaired erectile response to EFS in aged
      rats and raised it above the value for young rats, more efficiently than pCMV-PIN
      antisense RNA. PIN mRNA expression in the penis was decreased by >70% by the
      shRNA but remained unaffected by the antisense RNA, whereas PIN protein
      expression was reduced in both cases, particularly in the dorsal nerve. PIN
      antisense increased cGMP concentration in treated tissue by twofold. CONCLUSION:
      pSilencer2.1-U6-PIN-shRNA gene therapy was more effective than the antisense PIN
      mRNA in ameliorating ED in the aged rat, thereby suggesting that PIN is indeed a
      physiological inhibitor of nNOS and nitrergic neurotransmission in the penis.

PMID- 17433083
TI  - Enhanced external counterpulsation in patients with coronary artery disease
      associated erectile dysfunction. Part I: effects of risk factors.
AB  - INTRODUCTION: Recently it has been demonstrated that enhanced external
      counterpulsation (EECP) could improve erectile dysfunction (ED) in patients with
      refractory ischemic heart disease (IHD). AIM: To assess the effect of risk
      factors on the efficacy and the satisfaction rate of EECP in patients with
      coronary artery disease (CAD)-associated ED. MAIN OUTCOME MEASURES: To assess the
      effect of risk factors on EECP efficacy and satisfaction rate, we compared the
      pre- and post-EECP responses to erectile function domain, Q3, and Q4 in patients
      with and without risk factors. Overall satisfaction and global efficacy question
      (GEQ) were also assessed. METHODS: A total of 44 male consecutive patients with
      intractable angina caused by coronary insufficiency which cannot be controlled by
      conventional therapy were enrolled in this study. Patients were screened and
      followed up for ED using erectile function domain of the International Index for
      Erectile Function. A thorough sexual, medical, and psychosocial history was taken
      from all patients. RESULTS: All patients had severe diffuse triple vessels
      disease. They all had class III or IV angina. They were receiving the maximal
      antianginal pharmacotherapy. The mean age +/- SD was 57.1 +/- 5.6 years. Of the
      patients, 63.9% were below 60 years, and 86.4% were current or ex-smokers. There
      were significant differences between pre- and post-EECP regarding erectile
      function domain, Q3, and Q4. The sociodemographic variables were not
      significantly different among the studies groups and had not affected the GEQ or
      overall satisfaction. Overall satisfaction and GEQ were negatively influenced by
      smoking and presence of more than two risk factors. However, diabetes,
      hypertension, dyslipidemia, myocardial infraction, and obesity have not had such
      effects. CONCLUSIONS: The efficacy and satisfaction rate of EECP in patients with
      CAD-associated ED were negatively influenced by presence of risk factors;
      however, the global efficacy and the overall patients' satisfaction were
      encouraging.

PMID- 17433084
TI  - Simultaneous measurement of pelvic floor muscle activity and vaginal blood flow:
      a pilot study.
AB  - INTRODUCTION: Dyspareunia, defined as persistent or recurrent genital pain
      associated with sexual intercourse, is hypothesized to be related to pelvic floor
      hyperactivity and to diminished sexual arousal. Empirical research to support
      these hypotheses is scarce and concentrates mostly on the role of either pelvic
      floor activity or genital arousal in female dyspareunia. Currently, however,
      there is no measurement device to assess pelvic floor activity and genital
      response simultaneously. AIM: The aim of this study was to investigate the
      validity of a new device that enables simultaneous measurement of pelvic floor
      activity and genital response in women. MAIN OUTCOME MEASURES: Genital arousal
      measured as vaginal pulse amplitude, and vaginal surface electromyogram (EMG).
      METHOD: Thirty sexually functional women participated. To investigate the
      accuracy of genital response measurement with the adapted photoplethysmograph,
      and the sensitivity of the device for involuntary changes in pelvic floor
      activity, vaginal pulse amplitude and vaginal surface EMG were monitored during
      exposure to emotional, including erotic, films. In addition, vaginal surface EMG
      was monitored during instructed pelvic floor contractions. RESULTS: The genital
      data obtained during emotional films proved accurate measurement of genital
      response. EMG values during the emotional films indicated limited sensitivity of
      the device for small, involuntary changes in pelvic floor activity due to
      emotional state. The EMG measurements during the instructed pelvic floor
      contractions proved sensitivity of the new probe to voluntary pelvic floor
      activity. CONCLUSION: It is concluded that following improvement of the
      sensitivity of the EMG measurement for small, involuntary changes in pelvic floor
      activity, the device will be a valuable tool in research on superficial
      dyspareunia.

PMID- 17433085
TI  - Medical treatment of retrograde ejaculation in diabetic patients: a hope for
      spontaneous pregnancy.
AB  - INTRODUCTION: Retrograde ejaculation (RE) is one of the complications of diabetes
      mellitus. Different therapeutic approaches are present, whether medical or
      surgical, with limited success rates. AIM: The aim of the present study is to
      evaluate different drug regimens for the medical treatment of RE in diabetic
      patients. PATIENTS AND METHODS: Thirty-three diabetic patients with RE (23
      complete and 10 partial) were included in the study. Patients were given three
      sequential courses of medical treatment: imipramine 25 mg twice/day,
      pseudoephidrine 120 mg twice/day, or combination of the two drugs. MAIN OUTCOME
      MEASURES: Establishment of antegrade ejaculate in cases with complete RE and
      improvement of semen quality in case of partial RE. RESULTS: In cases with
      complete RE, imipramine was successful in producing antegrade ejaculate in 10
      patients (38.5%), while pseudoephedrine was successful in 11 patients (47.8%),
      and both drugs given together was successful in 16 patients (61.5%). In cases
      with partial RE, there was significant increase in the antegrade semen sample as
      regards semen volume, sperm count, total, and progressive motility with
      imipramine alone, pseudoephidrine alone, and both drugs. CONCLUSION: From the
      present study we can conclude that medical treatment for RE in diabetic patients
      is a promising method and should be the first line of treatment in these cases.

PMID- 17433086
TI  - Proposal for changes in diagnostic criteria for sexual dysfunctions.
AB  - INTRODUCTION: Officially sanctioned diagnostic criteria have a major influence on
      treatment decisions and on how populations are defined for clinical research. The
      Diagnostic and Statistical Manual of Mental Disorders (DSM) of the American
      Psychiatric Association has had a major influence on research concerning the
      treatment of sexual disorders and has been criticized on numerous grounds. AIM:
      The purpose of this article is to describe the evolution of criteria sets in the
      DSM and to critically evaluate suggestions for modification of this system.
      METHOD: All living members of the DSM work groups on sexual dysfunction were
      contacted regarding their recollections of the evolution of criteria sets.
      Literature concerning diagnostic criteria for the sexual dysfunctions in the DSM,
      as well as literature suggesting modification of this system, was reviewed. MAIN
      OUTCOME MEASURE: Recommendations for changes in the DSM-V system were based upon
      a review of the evidence concerning optimal criteria for each diagnostic entity.
      RESULTS: The original diagnostic system from sexual disorders in the DSM was
      developed by expert opinion, literature searches, and solicitation of feedback
      for other experts in the field. There have been minimal changes in the DSM
      criteria for sexual dysfunctions because of the requirement that there be
      substantial empirical data before modification of the system would be considered.
      An international consensus group has suggested major modification in criteria
      concerning female sexual dysfunctions. There is a growing database that documents
      the need to change criteria for premature ejaculation. CONCLUSIONS: It is
      recommended that some of the suggested modifications to the criteria sets for
      sexual dysfunctions be adopted by the DSM-V committee. It is also recommended
      that specific criteria related to duration and severity be adopted, in order to
      clearly distinguish sexual disorders from transient alterations in sexual
      function related to life stress and relationship discord.

PMID- 17433087
TI  - Sexual function after radical hysterectomy for early-stage cervical cancer.
AB  - INTRODUCTION: For early-stage cervical cancer, treatment with radical surgery
      appears effective with excellent survival. However, the treatment is associated
      with significant morbidities. Sexual dysfunction is the leading cause of symptom
      induced distress after the treatments for early-stage cervical cancer. There has
      been no study that evaluates the effect of surgical treatments for cervical
      cancer on sexual function in the Eastern/Asian patients. AIM: To examine the
      effect of radical hysterectomy on postoperative sexual function in women with
      early-stage cervical cancer. MAIN OUTCOME MEASURES. The visual analog score on
      seven aspects of sexual function: overall satisfaction with sexual intercourse,
      sexual desire, vaginal lubrication, vaginal elasticity, orgasmic satisfaction,
      patient-perceived partner satisfaction, and associated anxiety. METHODS: Thirty
      patients with International Federation of Gynecology and Obstetrics (FIGO) stage
      IB cervical cancer undergoing radical hysterectomy and pelvic lymphadenectomy at
      the Chiang Mai University Hospital were recruited. All of the patients were
      interviewed by questionnaire on sexual function at preoperative hospital
      admission and then at 3 and 6 months after surgery. Relevant clinical and
      pathologic data were also prospectively collected. RESULTS: The mean age of the
      patients was 45.3 +/- 6 years (range 28-59). Seven (23%) of the patients were
      postmenopausal. Almost all (97%) had FIGO stage IB1 disease. Fourteen (46.7%)
      patients had bilateral salpingo-oophorectomy, and one (3.3%) patient had
      unilateral salpingo-oophorectomy. Squamous-cell carcinoma and adenocarcinoma were
      diagnosed in 83% and 17%, respectively. At 3 and 6 months after operation, 63%
      and 93% of the patients had sexual intercourse, respectively. Considering the
      overall sexual satisfaction, the patient-rated visual analog score appeared
      comparable at preoperative and 6-month postoperative assessment (4.2 +/- 2.5 vs.
      3.6 +/- 2.2, P > 0.05). CONCLUSION: Radical hysterectomy using the current
      technique has a minimal short-term impact on sexual function. A comparative study
      with long-term follow-up would provide clearer information on permanent effect of
      radical hysterectomy on sexual function.

PMID- 17433088
TI  - Surgical outcomes and patient satisfaction after dermal, pericardial, and small
      intestinal submucosal grafting for Peyronie's disease.
AB  - INTRODUCTION: Peyronie's disease, a localized fibrosis of the tunica albuginea
      surrounding the penile corpora, results in penile curvature and sexual
      dysfunction. Surgical management involving grafting to straighten the penis is
      the treatment of choice in conditions unresponsive to conservative therapy where
      penile length preservation is important. AIM: To determine surgical outcomes and
      patient satisfaction after dermal, pericardial, and small intestinal submucosal
      grafting for Peyronie's disease. MAIN OUTCOME MEASURES: The International Index
      of Erectile Function (IIEF), postoperative self-reports, patient satisfaction,
      and clinical characteristics were used to measure outcomes. METHODS: We
      retrospectively reviewed charts of 36 patients who underwent surgery for
      Peyronie's disease requiring grafting from 1999 to 2005. Follow-up to
      subjectively assess outcomes was conducted. RESULTS: Average patient age at
      surgery was 55 +/- 1 years. Body mass indexes were similar among all groups.
      Erectile dysfunction risk factors were comparable with 36% reporting hypertension
      and 22% hypercholesterolemia. Overall patient follow-up time was 673 +/- 98 days.
      Self-reported resolution of penile curvature was noted in 60% of dermal, 100% of
      Tutoplast, and 76.9% of Stratasis graft recipients. Stratasis patients maintained
      presurgery length (54%) and rigidity (77%) more so than dermal (30%, 60%) and
      Tutoplast (23%, 39%) patients. Assessment of erectile dysfunction using the IIEF
      5 captured significant improvements in patients receiving Stratasis grafts
      (preoperative: 10.1 +/- 1.1 vs. postoperative: 17 +/- 1.6). Overall, 89% of
      patients reported satisfaction following surgical intervention. CONCLUSIONS:
      Surgical management of Peyronie's disease results in correction of penile
      curvatures and high rates of patient satisfaction. Loss of penile length and
      decreased rigidity occurred to a lesser degree with Stratasis grafts. While
      detailed informed consent is essential in this patient population, novel
      materials such as Tutoplast and Stratasis grafts improve outcomes following
      surgical correction of Peyronie's disease.

PMID- 17433089
TI  - Surrogate versus couple therapy in vaginismus.
AB  - INTRODUCTION: Women who do not have a cooperative partner cannot complete the
      usual therapeutic process in the treatment of vaginismus, because they cannot
      progress to the stage of practicing the insertion of the man partner's fingers
      and the insertion of a penis. AIM: To compare traditional couple therapy with
      therapy utilizing a surrogate partner. METHODS: The study was controlled and
      retrospective. Data were obtained from the treatment charts of patients who had
      come to the clinic for treatment of vaginismus. Sixteen vaginismus patients who
      were treated with a man surrogate partner were compared with 16 vaginismus
      patients who were treated with their own partners. MAIN OUTCOME MEASURES:
      Successful pain-free intercourse upon completion of therapy. RESULTS: One hundred
      percent of the surrogate patients succeeded in penile-vaginal intercourse
      compared with 75% in the couples group (P = 0.1). All surrogate patients ended
      the therapy because it was fully successful, compared with 69% in the couples
      group. Twelve percent of the couples group ended the therapy because it failed,
      and 19% because the couples decided to separate. CONCLUSIONS: Treating vaginismus
      with a man surrogate partner was at least as effective as couple therapy.
      Surrogate therapy may be considered for vaginismus patients who have no
      cooperative partner.

PMID- 17433090
TI  - Efficacy of an escalating dose regimen of pegylated interferon alpha-2a plus
      ribavirin in the early phase of HCV reinfection after liver transplantation.
AB  - We evaluated the safety and efficacy of an escalating dose regimen of pegylated
      interferon alpha-2a (PEG-IFN(alpha-2a)) and ribavirin in the early phase of
      recurrent hepatitis C after orthotopic liver transplantation (OLT). In this
      prospective study, 26 patients transplanted for hepatitis C virus cirrhosis with
      recurrent hepatitis C were treated 3.4 +/- 3.6 months after OLT and compared with
      an untreated historical control. PEG-IFN(alpha-2a) was initiated as monotherapy,
      following stepwise dose escalation up to 180 mug/week and the addition of
      ribavirin up to 1200 mg/day or maximally tolerated doses for 48 weeks. In the
      intent-to-treat analysis, 38% showed an early virological response (EVR), 35% an
      end of treatment response (ETR) and 19% a sustained virological response (SVR).
      SVR was associated with EVR (P = 0.0001) and cumulative PEG-IFN(alpha-2a) dose (P
      = 0.04). There was no significant histological improvement compared with
      untreated patients. There were no treatment-related serious adverse events.
      Adverse events included leucopenia (77%) and thrombocytopenia (46%). Three
      patients discontinued therapy due to side effects, fourteen were nonresponders
      and four relapsers. Treatment with PEG-IFN(alpha-2a) and ribavirin in the acute
      phase of post-transplant recurrent hepatitis C yielded an EVR of 38% and an SVR
      of 19%. The combination was safe and well tolerated.

PMID- 17433091
TI  - Abrogation of nephrotic proteinuria by rituximab treatment in a renal transplant
      patient with relapsed focal segmental glomerulosclerosis.
AB  - Relapse of focal segmental glomerulosclerosis (FSGS) after renal transplantation
      is 20-40%. Recurrence after a first relapse is 80%. The only current treatment is
      plasmapheresis and/or cyclophosphamide. We report successful treatment of a
      second relapse in a 48-year-old patient. At age 33, FSGS was diagnosed. The
      patient began hemodialysis 1 year later. In her first renal transplant, she
      developed recurrent FSGS and reached terminal transplant failure 3 years later.
      Eight years later, a second transplant was performed. Immunosuppressive regimen:
      steroids, mycophenolate mofetil (MMF), tacrolimus (TAC), and rabbit anti
      thymocyte globulin. Proteinuria of 2-6 g/day was detected and a biopsy showed
      recurrent FSGS. Plasmapheresis was started without success. Another biopsy still
      showed FSGS. The patient received two doses of rituximab (375 mg/m2 each) i.v.
      Three weeks later, proteinuria was 350 mg/day (serum-creatinine 1.6 mg/dl).
      Twelve months later, proteinuria was at 90 mg/day. Rituximab might be an option
      for recurrent FSGS after renal transplantation.

PMID- 17433092
TI  - Morphological and physiological changes of interstitial cells of Cajal after
      small bowel transplantation in rats.
AB  - Intestinal dysmotility has been reported to be associated with a decreased number
      of interstitial cells of Cajal (ICCs). However, the chronological changes in ICCs
      after small bowel transplantation (SBT) have not yet been elucidated. In this
      study, we aimed to evaluate the chronological change of ICCs after SBT.
      Orthotopic syngeneic SBT was performed in rats. Graft specimens were obtained at
      postreperfusion, and on 1, 3, 7, 14, and 30 postoperative day (POD). Thereafter,
      immunohistochemical staining was performed and the spontaneous contractions
      measured. During the initial period after SBT, the temporal impairment of ICCs
      was found. In an immunohistochemical study, c-Kit-positive cells appeared to
      decrease on POD 0, 1, and 3. Thereafter, the number of cells increased gradually
      up to POD 7. In contrast, the recovery of the spontaneous contractile amplitude
      took more time. The frequency of the electrical signal was preserved at almost
      exactly the same levels throughout this experimental period. Although the network
      of ICCs was found to be temporarily impaired after SBT in an immunohistochemical
      examination, this change was reversible. Moreover, the recovery of the function
      of the intestinal motility associated with ICCs was delayed after the early
      postoperative period.

PMID- 17433093
TI  - Differential engagement of anterior cingulate cortex subdivisions for cognitive
      and emotional function.
AB  - Functional differentiation of dorsal (dACC) and rostral (rACC) anterior cingulate
      cortex for cognitive and emotional function has received considerable indirect
      support. Using fMRI, parallel tasks, and within-subject analysis, the present
      study directly tested the proposed specialization of ACC subdivisions. A Task x
      Region interaction confirmed more dACC activation during color-word distractors
      and more rACC activation during emotion-word distractors. Activity in ACC
      subdivisions differentially predicted behavioral performance. Connectivity with
      prefrontal and limbic regions also supported distinct dACC and rACC roles.
      Findings provide direct evidence for differential engagement of ACC subdivisions
      in cognitive and emotional processing and for differential functional
      connectivity in the implementation of cognitive control and emotion regulation.
      Results point to an anatomical and functional continuum rather than segregated
      operations.

PMID- 17433094
TI  - Specificity of regional brain activity in anxiety types during emotion
      processing.
AB  - The present study tested the hypothesis that anxious apprehension involves more
      left- than right-hemisphere activity and that anxious arousal is associated with
      the opposite pattern. Behavioral and fMRI responses to threat stimuli in an
      emotional Stroop task were examined in nonpatient groups reporting anxious
      apprehension, anxious arousal, or neither. Reaction times were longer for
      negative than for neutral words. As predicted, brain activation distinguished
      anxious groups in a left inferior frontal region associated with speech
      production and in a right-hemisphere inferior temporal area. Addressing a second
      hypothesis about left-frontal involvement in emotion, distinct left frontal
      regions were associated with anxious apprehension versus processing of positive
      information. Results support the proposed distinction between the two types of
      anxiety and resolve an inconsistency about the role of left-frontal activation in
      emotion and psychopathology.

PMID- 17433095
TI  - Brain potentials in perception: picture complexity and emotional arousal.
AB  - Event-related potentials (ERPs) were measured while participants viewed
      affectively arousing and neutral pictures depicting either simple figure-ground
      compositions or more complex scenes to assess the timing and topography of
      perceptual and emotional modulation. Emotional pictures elicited a larger late
      positive potential than neutral pictures in a 400-700-ms window over centro
      parietal sensors both for pictures with simple figure-ground composition and for
      more complex scenes. Picture composition affected ERPs beginning earlier (around
      150 ms), with simple figure-ground compositions eliciting less positivity over
      posterior sensors and less negativity over frontal sensors. Emotionality had
      little effect on modulation of these early ERPs. These data suggest that the late
      centro-parietal positive potential primarily reflects motivational relevance, and
      that earlier posterior (and anterior) components reflect, at least in part,
      differences in a picture's perceptual organization.

PMID- 17433096
TI  - Difficulty of discrimination modulates attentional capture for deviant
      information.
AB  - It has been reported that an increased difficulty of discrimination between
      standard and target enhances P3a for typical nontarget. To elucidate the
      mechanism of this effect on deviant processing, the P300 event-related brain
      potential (ERP) was elicited using a visual three-stimulus oddball paradigm
      (standard circle, .70, target circle, .15, and nontarget/target square, .15).
      Four task conditions were defined by a combination of two category types of rare
      square (nontarget or target) and two levels of discrimination difficulty between
      standard and target circles (easy or difficult). In the difficult conditions, P3a
      was elicited by both nontarget and target square. Our findings suggest that the
      difficulty of discrimination between standard and target enhances attentional
      capture, rather than inhibition, for deviant information. This study has
      implications for understanding the attentional mechanisms of deviant processing.

PMID- 17433097
TI  - Sensitivity to masked conditioned stimuli predicts conditioned response magnitude
      under masked conditions.
AB  - Expression of conditioned fear has been reported to be independent of perceptual
      awareness of conditioned stimuli (CSs). Previous studies have been criticized,
      however, for not adequately assessing perceptual awareness. We fear-conditioned
      participants to one of two symbols and measured skin conductance responses to
      dichoptically masked and unmasked CSs. Participants also performed a target
      detection task and sensitivity (d') to the masked conditioned stimuli (CS+, CS-)
      was measured. Results showed that sensitivity under masking conditions was
      related to conditioned responses to masked CSs but not unmasked CSs. Thus, a
      strong relationship between expression of conditioned fear and awareness of the
      CS+ emerges when the latter is assessed by signal detection methods. Without
      consensus on how awareness should be defined, these findings bring balance to
      previous studies that have typically used less sensitive assessments of
      awareness.

PMID- 17433098
TI  - Psychomotor speed in hypertension: effects of reaction time components, stimulus
      modality, and phase of the cardiac cycle.
AB  - Hypertension is characterized by cognitive deficits. As evidence for impaired
      psychomotor speed, including slower reaction times, is mixed, we aimed to provide
      a detailed investigation of simple reaction time in hypertension. Pre-motor and
      motor reaction times were measured across the cardiac cycle in 30 hypertensives
      and 29 normotensives to determine the effects of phasic and tonic blood pressure
      on performance. Auditory, visual, and tactile simple reaction time tasks were
      completed with stimuli presented 0, 300, and 600 ms after the R-wave of the
      electrocardiogram. Reaction times did not differ between hypertensives and
      normotensives. Although pre-motor reaction times were faster during the late
      phase than the early phase of the cardiac cycle whereas motor reaction times were
      unchanged, this effect was similar for hypertensives and normotensives. No
      sensory-motor deficits were evident in these hypertensives regardless of
      baroreceptor activity.

PMID- 17433099
TI  - Untangling syntactic and sensory processing: an ERP study of music perception.
AB  - The present study investigated music-syntactic processing with chord sequences
      that ended on either regular or irregular chord functions. Sequences were
      composed such that perceived differences in the cognitive processing between
      syntactically regular and irregular chords could not be due to the sensory
      processing of acoustic factors like pitch repetition, pitch commonality (the
      major component of "sensory dissonance"), or roughness. Three experiments with
      independent groups of subjects were conducted: a behavioral experiment and two
      experiments using electroencephalography. Irregular chords elicited an early
      right anterior negativity (ERAN) in the event-related brain potentials (ERPs)
      under both task-relevant and task-irrelevant conditions. Behaviorally,
      participants detected around 75% of the irregular chords, indicating that these
      chords were only moderately salient. Nevertheless, the irregular chords reliably
      elicited clear ERP effects. Amateur musicians were slightly more sensitive to
      musical irregularities than nonmusicians, supporting previous studies
      demonstrating effects of musical training on music-syntactic processing. The
      findings indicate that the ERAN is an index of music-syntactic processing and
      that the ERAN can be elicited even when irregular chords are not detectable based
      on acoustical factors such as pitch repetition, sensory dissonance, or roughness.

PMID- 17433100
TI  - The College of Medicine in the Republic of Malawi: towards sustainable staff
      development.
AB  - BACKGROUND: Malawi has a critical human resources problem particularly in the
      health sector. There is a severe shortage of doctors; there are only few medical
      specialists. The College of Medicine (COM) is the only medical school and was
      founded in 1991. For senior staff it heavily depends on expatriates. In 2004 the
      COM started its own postgraduate training programme (Master of Medicine) in the
      clinical specialties. METHODS: We explore to what extent a brain drain took place
      among the COM graduates by investigating their professional development and
      geographical distribution. Using current experience with the postgraduate
      programme, we estimate at what point all senior academic positions in the
      clinical departments could be filled by Malawians. We demonstrate the need for
      expatriate staff for its most senior academic positions in the interim period and
      how this can be phased out. Lastly we reflect on measures that may influence the
      retention of Malawian doctors. RESULTS: Since the start of the COM 254 students
      have graduated with an average of 17 students per year. Most (60%) are working in
      Malawi. Of those working abroad, 60% are in various postgraduate training
      programmes. In 2015, adequate numbers of Malawi senior academics should be
      available to fill most senior positions in the clinical departments, taking into
      account a 65% increase in staff to cope with increasing numbers of students.
      CONCLUSION: There seems to be no significant brain drain among graduates of the
      COM. The postgraduate programme is in place to train graduates to become senior
      academic staff. In the interim, the COM depends heavily upon expatriate input for
      its most senior academic positions. This will be necessary at least until 2015
      when sufficient numbers of well trained and experienced Malawian specialists may
      be expected to be available. Improved pay structure and career development
      perspectives will be essential to consolidate the trend that most doctors will
      remain in the country.

PMID- 17433101
TI  - Time-trend and variations in the proportion of second-eye cataract surgery.
AB  - BACKGROUND: Despite recommendations for greater use of second-eye cataract
      surgery and the bilateral progression of the disease, there is a substantial
      proportion of unmet need for this treatment. Few studies have explored the
      factors associated with second-eye cataract surgery utilisation. The objective of
      our study was to estimate the proportion of second-eye cataract surgery, evaluate
      its time-trend, and explore differences in utilisation by patients' gender, age,
      and region of residence. METHODS: All senile cataract surgeries performed between
      1999 and 2002 in the public health system of Catalonia (Spain) were obtained from
      the Minimum Data Set. The proportion of second-eye surgery from November 2000 to
      December 2002 was calculated. The time-trend of this proportion was characterised
      through linear regression models with the logarithmic transformation of time.
      RESULTS: The proportion of second-eye surgery was 30.0% and showed an increasing
      trend from 24.8% (95% Confidence Interval [CI] 21.6; 26.1) in November 2000 to
      31.8% (95% CI 31.4; 33.6) in December 2002. This proportion was 1.9% (95% CI 0.9;
      2.9) higher in women (p < 0.001) and held constant across time. Male patients
      aged less than 60 had the lowest proportion (22.6%; 95% CI 22.4; 22.9) and
      females between 70 and 79 had the highest proportion (27.4%; 95% CI 26.9; 27.9).
      The time-trend for the proportion of second-eye surgery in those aged over 80
      years was greater than for younger ages, showing an increase of 9% at the end of
      the period for both males and females. Variations between regions decreased over
      time because regions with the lowest initial proportions of second-eye surgery
      (approximately 17%) showed a greater increase over the study period. CONCLUSION:
      We predict greater utilization of second-eye surgery in patients aged 70 to 79
      years and in women. A greater increase in the utilisation rates of second-eye
      surgery is expected in the regions with lower proportions and in older patients.
      The observed trend suggests that there will be a substantial proportion of unmet
      need for bilateral surgery.

PMID- 17433103
TI  - Interactions between estrogen- and Ah-receptor signalling pathways in primary
      culture of salmon hepatocytes exposed to nonylphenol and 3,3',4,4'
      tetrachlorobiphenyl (congener 77).
AB  - BACKGROUND: The estrogenic and xenobiotic biotransformation gene expressions are
      receptor-mediated processes that are ligand structure-dependent interactions with
      estrogen-receptor (ER) and aryl hydrocarbon receptor (AhR), probably involving
      all subtypes and other co-factors. The anti-estrogenic activities of AhR agonists
      have been reported. In teleost fish, exposure to AhR agonists has been associated
      with reduced Vtg synthesis or impaired gonadal development in both in vivo- and
      in vitro studies. Inhibitory AhR and ER cross-talk have also been demonstrated in
      breast cancer cells, rodent uterus and mammary tumors. Previous studies have
      shown that AhR-agonists potentiate xenoestrogen-induced responses in fish in vivo
      system. Recently, several studies have shown that AhR-agonists directly activate
      ER alpha and induce estrogenic responses in mammalian in vitro systems. In this
      study, two separate experiments were performed to study the molecular
      interactions between ER and AhR signalling pathways using different concentration
      of PCB-77 (an AhR-agonist) and time factor, respectively. Firstly, primary
      Atlantic salmon hepatocytes were exposed to nonylphenol (NP: 5 microM--an ER
      agonist) singly or in combination with 0.001, 0.01 and 1 microM PCB-77 and
      sampled at 48 h post-exposure. Secondly, hepatocytes were exposed to NP (5
      microM) or PCB-77 (1 microM) singly or in combination for 12, 24, 48 and 72 h.
      Samples were analyzed using a validated real-time PCR for genes in the ER pathway
      or known to be NP-responsive and AhR pathway or known to be PCB-77 responsive.
      RESULTS: Our data showed a reciprocal inhibitory interaction between NP and PCB
      77. PCB-77 produced anti-NP-mediated effect by decreasing the mRNA expression of
      ER-responsive genes. NP produced anti-AhR mediated effect or as inhibitor of AhR
      alpha, AhRR, ARNT, CYP1A1 and UDPGT expression. A novel aspect of the present
      study is that low (0.001 microM) and medium (0.01 microM) PCB-77 concentrations
      increased ER alpha mRNA expression above control and NP exposed levels, and at 12
      h post-exposure, PCB-77 exposure alone produced significant elevation of ER
      alpha, ER beta and Zr-protein expressions above control levels. CONCLUSION: The
      findings in the present study demonstrate a complex mode of ER-AhR interactions
      that were dependent on time of exposure and concentration of individual chemicals
      (NP and PCB-77). This complex mode of interaction is further supported by the
      effect of PCB-77 on ER alpha and ER beta (shown as increase in transcription)
      with no concurrent activation of Vtg (but Zr-protein) response. These complex
      interactions between two different classes of ligand-activated receptors provide
      novel mechanistic insights on signalling pathways. Therefore, the degree of
      simultaneous interactions between the ER and AhR gene transcripts demonstrated in
      this study supports the concept of cross-talk between these signalling pathways.

PMID- 17433104
TI  - Two inbred rat strains contrasting for anxiety-related behaviors show similar
      levels of defensive responses to cat odor.
AB  - Rodents are known to display fear-related responses when exposed to the odor of
      natural predators, such as cats, even when they are totally naive to these
      stimuli. Based on that, a behavioral test in which rats are exposed to cat odor
      has been developed and proposed to model some forms of anxiety. The objective of
      the present study was thus to compare the LEW (Lewis) and SHR (spontaneously
      hypertensive rats) inbred rat strains, which display genetic differences in other
      classical models of anxiety, in the cat odor test. As expected, cat odor produced
      an increase in fear-related behaviors. However, no clear differences were found
      between the two strains tested. These results suggest that the type of stress
      experienced by LEW and SHR strains exposed to cat odor is different from that
      elicited by exposure to classical models of anxiety such as the elevated plus
      maze, black/white box and open-field tests.

PMID- 17433105
TI  - Analyzing factors that influence the folk use and phytonomy of 18 medicinal
      plants in Navarra.
AB  - BACKGROUND: This article analyzes whether the distribution or area of use of 18
      medicinal plants is influenced by ecological and cultural factors which might
      account for their traditional use and/or phytonymy in Navarra. This discussion
      may be helpful for comparative studies, touching as it does on other
      ethnopharmacological issues: a) which cultural and ecological factors affect the
      selection of medicinal plants; b) substitutions of medicinal plants in popular
      medicine; c) the relation between local nomenclature and uses. To analyze these
      questions, this paper presents an example of a species used for digestive
      disorders (tea and camomile: Jasonia glutinosa, J. tuberosa, Sideritis
      hyssopifolia, Bidens aurea, Chamaemelum nobile, Santolina chamaecyparissus...),
      high blood pressure (Rhamnus alaternus, Olea europaea...) or skin diseases
      (Hylotelephium maximum, H. telephium, Anagallis arvensis, A. foemina). METHODS:
      Fieldwork began on January 2004 and continued until December 2006. During that
      time we interviewed 505 informants in 218 locations in Navarra. Information was
      collected using semi-structured ethnobotanical interviews, and we subsequently
      made maps using Arc-View 8.0 program to determine the area of use of each taxon.
      Each map was then compared with the bioclimatic and linguistic map of Navarra,
      using the soil and ethnographic data for the region, and with other
      ethnobotanical and ethnopharmacological studies carried out in Europe. RESULTS:
      The results clearly show that ecological and cultural factors influence the
      selection of medicinal plants in this region. Climate and substrate are the most
      important ecological factors that influence the distribution and abundance of
      plants, which are the biological factors that affect medicinal plant selection.
      CONCLUSION: The study of edaphological and climatological factors, on the one
      hand, and culture, on the other, can help us to understand why a plant is
      replaced by another one for the same purposes, either in the same or in a
      different area. In many cases, the cultural factor means that the use of a
      species is more widespread than its ecological distribution. This may also
      explain the presence of synonyms and polysemies which are useful for discussing
      ethnopharmacological data.

PMID- 17433106
TI  - Analysis of epistatic interactions and fitness landscapes using a new geometric
      approach.
AB  - BACKGROUND: Understanding interactions between mutations and how they affect
      fitness is a central problem in evolutionary biology that bears on such
      fundamental issues as the structure of fitness landscapes and the evolution of
      sex. To date, analyses of fitness landscapes have focused either on the overall
      directional curvature of the fitness landscape or on the distribution of pairwise
      interactions. In this paper, we propose and employ a new mathematical approach
      that allows a more complete description of multi-way interactions and provides
      new insights into the structure of fitness landscapes. RESULTS: We apply the
      mathematical theory of gene interactions developed by Beerenwinkel et al. to a
      fitness landscape for Escherichia coli obtained by Elena and Lenski. The
      genotypes were constructed by introducing nine mutations into a wild-type strain
      and constructing a restricted set of 27 double mutants. Despite the absence of
      mutants higher than second order, our analysis of this genotypic space points to
      previously unappreciated gene interactions, in addition to the standard pairwise
      epistasis. Our analysis confirms Elena and Lenski's inference that the fitness
      landscape is complex, so that an overall measure of curvature obscures a
      diversity of interaction types. We also demonstrate that some mutations
      contribute disproportionately to this complexity. In particular, some mutations
      are systematically better than others at mixing with other mutations. We also
      find a strong correlation between epistasis and the average fitness loss caused
      by deleterious mutations. In particular, the epistatic deviations from
      multiplicative expectations tend toward more positive values in the context of
      more deleterious mutations, emphasizing that pairwise epistasis is a local
      property of the fitness landscape. Finally, we determine the geometry of the
      fitness landscape, which reflects many of these biologically interesting
      features. CONCLUSION: A full description of complex fitness landscapes requires
      more information than the average curvature or the distribution of independent
      pairwise interactions. We have proposed a mathematical approach that, in
      principle, allows a complete description and, in practice, can suggest new
      insights into the structure of real fitness landscapes. Our analysis emphasizes
      the value of non-independent genotypes for these inferences.

PMID- 17433107
TI  - HHV-8 encoded LANA-1 alters the higher organization of the cell nucleus.
AB  - The latency-associated nuclear antigen (LANA-1) of Human Herpes Virus 8 (HHV-8),
      alternatively called Kaposi Sarcoma Herpes Virus (KSHV) is constitutively
      expressed in all HHV-8 infected cells. LANA-1 accumulates in well-defined foci
      that co-localize with the viral episomes. We have previously shown that these
      foci are tightly associated with the borders of heterochromatin 1. We have also
      shown that exogenously expressed LANA-1 causes an extensive re-organization of
      Hoechst 33248 DNA staining patterns of the nuclei in non-HHV-8 infected cells 2.
      Here we show that this effect includes the release of the bulk of DNA from
      heterochromatic areas, in both human and mouse cells, without affecting the
      overall levels of heterochromatin associated histone H3 lysine 9 tri-methylation
      (3MK9H3). The release of DNA from the heterochromatic chromocenters in LANA-1
      transfected mouse cells co-incides with the dispersion of the chromocenter
      associated methylcytosin binding protein 2 (MECP2). The localization of 3MK9H3 to
      the remnants of the chromocenters remains unaltered. Moreover, exogeneously
      expressed LANA-1 leads to the relocation of the chromocenters to the nuclear
      periphery, indicating extensive changes in the positioning of the chromosomal
      domains in the LANA-1 harboring interphase nucleus. Using a series of deletion
      mutants we have shown that the chromatin rearranging effects of LANA-1 require
      the presence of a short (57 amino acid) region that is located immediately
      upstream of the internal acidic repeats. This sequence lies within the previously
      mapped binding site to histone methyltransferase SUV39H1. We suggest that the
      highly concentrated LANA-1, anchored to the host genome in the nuclear foci of
      latently infected cells and replicated through each cell generation, may function
      as "epigenetic modifier". The induction of histone modification in adjacent host
      genes may lead to altered gene expression, thereby contributing to the viral
      oncogenesis.

PMID- 17433108
TI  - Centrosome and retroviruses: the dangerous liaisons.
AB  - Centrosomes are the major microtubule organizing structures in vertebrate cells.
      They localize in close proximity to the nucleus for the duration of interphase
      and play major roles in numerous cell functions. Consequently, any deficiency in
      centrosome function or number may lead to genetic instability. Several viruses
      including retroviruses such as, Foamy Virus, HIV-1, JSRV, M-PMV and HTLV-1 have
      been shown to hamper centrosome functions for their own profit, but the outcomes
      are very different. Foamy viruses, HIV-1, JSRV, M-PMV and HTLV-1 use the cellular
      machinery to traffic towards the centrosome during early and/or late stages of
      the infection. In addition HIV-1 Vpr protein alters the cell-cycle regulation by
      hijacking centrosome functions. Enthrallingly, HTLV-1 Tax expression also targets
      the functions of the centrosome, and this event is correlated with centrosome
      amplification, aneuploidy and transformation.

PMID- 17433110
TI  - Meeting report on the first Iranian congress of electrodiagnosis in peripheral
      nerve lesions.
AB  - The Department of Physical Medicine, Rehabilitation and Electrodiagnosis of
      Shaheed Beheshti Medical University in collaboration with the Iranian Society of
      Physical Medicine and Rehabilitation (ISPMR) held the 1st Congress of
      Electrodiagnostic Medicine in Peripheral Nerve Lesions on December 21-22, 2006.
      Electrodiagnostic medicine is a specific branch of medicine used by specialist
      physicians in the field of physical medicine and rehabilitation and/or neurology
      to diagnose, prognosticate and plan treatment options of peripheral nerve
      lesions. This meeting was hold to discuss multidisciplinary approaches to this
      common and important topic in the medical field.

PMID- 17433109
TI  - NOGO-A induction and localization during chick brain development indicate a role
      disparate from neurite outgrowth inhibition.
AB  - BACKGROUND: Nogo-A, a myelin-associated protein, inhibits neurite outgrowth and
      abates regeneration in the adult vertebrate central nervous system (CNS) and may
      play a role in maintaining neural pathways once established. However, the
      presence of Nogo-A during early CNS development is counterintuitive and hints at
      an additional role for Nogo-A beyond neurite inhibition. RESULTS: We isolated
      chicken NOGO-A and determined its sequence. A multiple alignment of the amino
      acid sequence across divergent species, identified five previously undescribed,
      Nogo-A specific conserved regions that may be relevant for development. NOGO gene
      transcripts (NOGO-A, NOGO-B and NOGO-C) were differentially expressed in the CNS
      during development and a second NOGO-A splice variant was identified. We further
      localized NOGO-A expression during key phases of CNS development by in situ
      hybridization. CNS-associated NOGO-A was induced coincident with neural plate
      formation and up-regulated by FGF in the transformation of non-neural ectoderm
      into neural precursors. NOGO-A expression was diffuse in the neuroectoderm during
      the early proliferative phase of development, and migration, but localized to
      large projection neurons of the optic tectum and tectal-associated nuclei during
      architectural differentiation, lamination and network establishment. CONCLUSION:
      These data suggest Nogo-A plays a functional role in the determination of neural
      identity and/or differentiation and also appears to play a later role in the
      networking of large projection neurons during neurite formation and
      synaptogenesis. These data indicate that Nogo-A is a multifunctional protein with
      additional roles during CNS development that are disparate from its later role of
      neurite outgrowth inhibition in the adult CNS.

PMID- 17433111
TI  - Pyoderma gangrenosum--a review.
AB  - Pyoderma gangrenosum (PG) is a rare noninfectious neutrophilic dermatosis.
      Clinically it starts with sterile pustules that rapidly progress and turn into
      painful ulcers of variable depth and size with undermined violaceous borders. The
      legs are most commonly affected but other parts of the skin and mucous membranes
      may also be involved. Course can be mild or malignant, chronic or relapsing with
      remarkable morbidity. In many cases PG is associated with an underlying disease,
      most commonly inflammatory bowel disease, rheumatic or haematological disease and
      malignancy. Diagnosis of PG is based on history of an underlying disease, typical
      clinical presentation, histopathology, and exclusion of other diseases that would
      lead to a similar appearance. The peak of incidence occurs between the ages of 20
      to 50 years with women being more often affected than men. Aetiology has not been
      clearly determined yet. The treatment of PG is a challenge. Randomized, double
      blinded prospective multicenter trials for PG are not available. The best
      documented treatments are systemic corticosteroids and cyclosporin A.
      Combinations of steroids with cytotoxic drugs are used in resistant cases. The
      combination of steroids with sulfa drugs or immunosuppressants has been used as
      steroid-sparing modalities. Anti-tumor necrosis alpha therapy in Crohn's disease
      showed a rapid response of PG. Skin transplants and the application of
      bioengineered skin is useful in selected cases as a complement to the
      immunosuppressive treatment. Topical therapy with modern wound dressings is
      useful to minimize pain and the risk of secondary infections. Despite recent
      advances in therapy, the prognosis of PG remains unpredictable.

PMID- 17433112
TI  - Minimally invasive cardiopulmonary bypass: does it really change the outcome?
AB  - INTRODUCTION: Many innovative cardiopulmonary bypass (CPB) systems have recently
      been proposed by the industry. With few differences, they all share a philosophy
      based on priming volume reduction, closed circuit with separation of the surgical
      field suction, centrifugal pump, and biocompatible circuit and oxygenator. These
      minimally invasive CPB (MICPB) systems are intended to limit the deleterious
      effects of a conventional CPB. However, no evidence exists with respect to their
      effectiveness in improving the postoperative outcome in a large population of
      patients. This study aimed to verify the clinical impact of an MICPB in a large
      population of patients undergoing coronary artery revascularization. METHODS: We
      conducted a retrospective analysis of 1,663 patients treated with an MICPB. The
      control group (conventional CPB) was extracted from a series of 2,877 patients
      according to a propensity score analysis. RESULTS: Patients receiving an MICPB
      had a shorter intensive care unit (ICU) stay, had lower peak postoperative serum
      creatinine and bilirubin levels, and suffered less postoperative blood loss.
      Within a multivariable model, MICPB is independently associated with lower rates
      of atrial fibrillation (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.69
      to 0.99) and ventricular arrhythmias (OR 0.45, 95% CI 0.28 to 0.73) and with
      higher rates of early discharge from the ICU (OR 1.31, 95% CI 1.06 to 1.6) and
      from the hospital (OR 1.46, 95% CI 1.18 to 1.8). Hospital mortality did not
      differ between groups. CONCLUSION: MICPBs are associated with reduced morbidity.
      However, these results will need to be confirmed in a large, prospective,
      randomized, controlled trial.

PMID- 17433113
TI  - Cyclophosphamide "metronomic" chemotherapy for palliative treatment of a young
      patient with advanced epithelial ovarian cancer.
AB  - BACKGROUND: Evaluation of the clinical efficacy and tolerance of metronomic
      chemotherapy as salvage therapy in a young patient with advanced, platinum
      resistant, ovarian carcinoma and bad performance status. CASE PRESENTATION: We
      tried palliative chemotherapy with daily low dose oral cyclophosphamide with a
      patient suffering from stage IIIC ovarian cancer that responded to daily
      cyclophosphamide (CTX) after no response to chemotherapy with paclitaxel and
      carboplatin as first line and progression after second line with topotecan. The
      progression-free survival time on daily low dose oral cyclophosphamide treatment
      was 65 months without side effects. She was well during the chemotherapy and
      lived a normal working and social life. CONCLUSION: We think that use of low dose
      of oral CTX should be investigated further as a strategy against tumour
      progression after standard chemotherapy in patients who are platinum resistant
      with poor performance status.

PMID- 17433114
TI  - Wild vascular plants gathered for consumption in the Polish countryside: a
      review.
AB  - BACKGROUND: This paper is an ethnobotanical review of wild edible plants gathered
      for consumption from the end of the 18th century to the present day, within the
      present borders of Poland. METHODS: 42 ethnographic and botanical sources
      documenting the culinary use of wild plants were analyzed. RESULTS: The use of
      112 species (3.7% of the flora) has been recorded. Only half of them have been
      used since the 1960s. Three species: Cirsium rivulare, Euphorbia peplus and
      Scirpus sylvaticus have never before been reported as edible by ethnobotanical
      literature. The list of wild edible plants which are still commonly gathered
      includes only two green vegetables (Rumex acetosa leaves for soups and Oxalis
      acetosella as children's snack), 15 folk species of fruits and seeds (Crataegus
      spp., Corylus avellana, Fagus sylvatica, Fragaria vesca, Malus domestica, Prunus
      spinosa, Pyrus spp., Rosa canina, Rubus idaeus, Rubus sect. Rubus, Sambucus
      nigra, Vaccinium myrtillus, V. oxycoccos, V. uliginosum, V. vitis-idaea) and four
      taxa used for seasoning or as preservatives (Armoracia rusticana root and leaves,
      Carum carvi seeds, Juniperus communis pseudo-fruits and Quercus spp. leaves). The
      use of other species is either forgotten or very rare. In the past, several
      species were used for food in times of scarcity, most commonly Chenopodium album,
      Urtica dioica, U. urens, Elymus repens, Oxalis acetosella and Cirsium spp., but
      now the use of wild plants is mainly restricted to raw consumption or making
      juices, jams, wines and other preserves. The history of the gradual disappearance
      of the original barszcz, Heracleum sphondylium soup, from Polish cuisine has been
      researched in detail and two, previously unpublished, instances of its use in the
      20th century have been found in the Carpathians. An increase in the culinary use
      of some wild plants due to media publications can be observed. CONCLUSION: Poland
      can be characterized as a country where the traditions of culinary use of wild
      plants became impoverished very early, compared to some parts of southern Europe.
      The present use of wild plants, even among the oldest generation, has been almost
      entirely restricted to fruits.

PMID- 17433115
TI  - Proteinase-activated receptor 4 stimulation-induced epithelial-mesenchymal
      transition in alveolar epithelial cells.
AB  - BACKGROUND: Proteinase-activated receptors (PARs; PAR1-4) that can be activated
      by serine proteinases such as thrombin and neutrophil catepsin G are known to
      contribute to the pathogenesis of various pulmonary diseases including fibrosis.
      Among these PARs, especially PAR4, a newly identified subtype, is highly
      expressed in the lung. Here, we examined whether PAR4 stimulation plays a role in
      the formation of fibrotic response in the lung, through alveolar epithelial
      mesenchymal transition (EMT) which contributes to the increase in myofibroblast
      population. METHODS: EMT was assessed by measuring the changes in each specific
      cell markers, E-cadherin for epithelial cell, alpha-smooth muscle actin (alpha
      SMA) for myofibroblast, using primary cultured mouse alveolar epithelial cells
      and human lung carcinoma-derived alveolar epithelial cell line (A549 cells).
      RESULTS: Stimulation of PAR with thrombin (1 U/ml) or a synthetic PAR4 agonist
      peptide (AYPGKF-NH2, 100 muM) for 72 h induced morphological changes from
      cobblestone-like structure to elongated shape in primary cultured alveolar
      epithelial cells and A549 cells. In immunocytochemical analyses of these cells,
      such PAR4 stimulation decreased E-cadherin-like immunoreactivity and increased
      alpha-SMA-like immunoreactivity, as observed with a typical EMT-inducer, tumor
      growth factor-beta (TGF-beta). Western blot analyses of PAR4-stimulated A549
      cells also showed similar changes in expression of these EMT-related marker
      proteins. Such PAR4-mediated changes were attenuated by inhibitors of epidermal
      growth factor receptor (EGFR) kinase and Src. PAR4-mediated morphological changes
      in primary cultured alveolar epithelial cells were reduced in the presence of
      these inhibitors. PAR4 stimulation increased tyrosine phosphorylated EGFR or
      tyrosine phosphorylated Src level in A549 cells, and the former response being
      inhibited by Src inhibitor. CONCLUSION: PAR4 stimulation of alveolar epithelial
      cells induced epithelial-mesenchymal transition (EMT) as monitored by cell
      shapes, and epithelial or myofibroblast marker at least partly through EGFR
      transactivation via receptor-linked Src activation.

PMID- 17433116
TI  - The ethics of CYP2D6 testing for patients considering tamoxifen.
AB  - The CYP2D6 gene is responsible for the majority of tamoxifen metabolism. Recent
      compelling, yet limited data have determined that postmenopausal women who carry
      a functional polymorphism in the CYP2D6 gene have a worse clinical outcome than
      women who have a wild-type genotype. In this commentary we discuss the level of
      evidence needed to change clinical practice and whether CYP2D6 genotyping is
      appropriate for all women considering tamoxifen as part of their adjuvant
      therapy.

PMID- 17433117
TI  - Annual Meeting of the Study Group Neurochemistry. International Conference of the
      Gesellschaft fur Biochemie und Molekularbiologie 2006 (GBM 2006): molecular
      pathways in health and disease of the nervous system. Witten, Germany. September
      28-30, 2006. Abstracts.

PMID- 17433118
TI  - The relationship between suicide rates and age: an analysis of multinational data
      from the World Health Organization.
AB  - BACKGROUND: Suicide rates generally increase with age. With the emergence of
      studies from several countries without an increase in suicides rates with aging,
      a cross-national study examining the relationship between suicide rates and age
      was undertaken. METHODS: The relationship between suicide rates and age was
      examined by ascertaining suicide rates in both sexes in seven age-bands 16-24
      years, 25-34 years, 35-44 years, 45-54 years, 55-64 years, 65-74 years and 75+
      years, from the World Health Organization website for all the listed countries (N
      = 62). RESULTS: The main findings were: (i) there was a significant increase in
      suicide rates with increasing age in males and females in 25 and 27 countries
      respectively; (ii) there was no significant increase in suicide rates with
      increasing age in males and females in 31 and 29 countries respectively; (iii)
      suicide rates were the highest in the younger age-bands in countries without a
      significant increase in male suicides rates with increasing age; (iv) countries
      without a significant increase in the suicide rate with increasing age in both
      sexes, females only and males only demonstrated regional clustering; and, (v) in
      a small number of countries suicide rates declined with increasing age.
      CONCLUSIONS: Potential explanations for regional and cross-national variations in
      the relationship between suicide rates and age require further study.

PMID- 17433119
TI  - The diagnosis of dementia in the community.
AB  - BACKGROUND: Different interview schedules and diagnostic criteria for dementia
      have contributed to differing incidence and prevalence rates. AIM: This study
      aimed to examine the effect of different diagnostic criteria on the prevalence of
      dementia in the community. METHODS: Some 1000 subjects (>65 years) were recruited
      in Kaniyambadi Block, Vellore, India, using a one-stage assessment procedure.
      RESULTS: The prevalence of dementia by Diagnostic and Statistical Manual IV
      standard, the Community Screening instrument for Dementia DF Score, the education
      adjusted 10/66 Dementia Research Group criteria, and the Geriatric Mental State
      was 0.8%, 6.2%, 10.6%, 63.2% respectively. CONCLUSION: Differences in
      information, interview schedules, diagnostic criteria and settings contribute to
      variation in identification of people with dementia. Minor variations in criteria
      have a significant impact on diagnosis. The assessment of the clinical state is
      influenced by education, level of baseline function, impairment in current
      functioning, life style and demands on the person, tolerance of impairment and
      expectation by relatives and by differences between patients attending hospitals
      and those living in the community. The variation in rates demands a debate on the
      criteria for dementia in the community in general and for less literate
      populations in particular.

PMID- 17433120
TI  - Five-year trajectories of social networks and social support in older adults with
      major depression.
AB  - BACKGROUND: Research with nondepressed adults suggests that social networks and
      social support are stable over the life course until very late age. This may not
      hold true for older adults with depression. We examined baseline status and
      trajectories of social networks and social support at the group and individual
      levels over five years. METHODS: The sample consisted of 339 initially depressed
      adults aged 59 or older (M = 69 years) enrolled in a naturalistic study of
      depression. Measures of social ties, including social network size, frequency of
      interaction, instrumental support, and subjective support, were administered at
      baseline and yearly for five years. RESULTS: Latent growth curve models were
      estimated for each aspect of social ties. On average, social network size and
      frequency of interaction were low at baseline and remained stable over time,
      whereas subjective and instrumental support were high at baseline yet increased
      over time. There was significant variation in the direction and rate of change
      over time, which was not predicted by demographic or clinical factors.
      CONCLUSIONS: Because increasing social networks may be ineffective and may not be
      possible for a portion of people who already receive maximal support,
      interventions to increase social support may only work for a portion of older
      depressed adults.

PMID- 17433121
TI  - Outcome measures in clinical trials on medicinal products for the treatment of
      dementia: a European regulatory perspective.
AB  - Based on efficacy and safety data, several drugs have been approved for
      symptomatic improvement of dementia of the Alzheimer type and one for the
      symptomatic improvement of dementia associated with Parkinson's disease. However,
      established treatment effects must be considered as modest. Randomized clinical
      trials in other subtypes of dementia (e.g. vascular dementia) have not been able
      to demonstrate clinically relevant symptomatic improvement, nor has it yet been
      possible to establish disease-modifying effects in any dementia syndrome or its
      subtypes. Recent progress in basic science and molecular biology of the dementias
      has now fostered new interest for more efficacious symptomatic treatments as well
      as for disease-modifying approaches in the degenerative dementias. For regulatory
      purposes this requires better standardization and refinement of diagnostic
      criteria, which allow the study of homogeneous disease populations in specialized
      academic centers as well as in the general community setting. Depending on the
      disease stages (early versus late, mild to moderate to severe impairment) and
      disease entities, distinct assessment tools for cognitive, functional and global
      endpoints should be used or newly developed. The typical design to show
      symptomatic improvement is a randomized, double-blind, placebo-controlled,
      parallel group study comparing change in two primary endpoints, one of them
      reflecting the cognitive domain and the second preferably reflecting the
      functional domain of impairment. The changes must be robust and clinically
      meaningful in favor of active treatment versus placebo. If a treatment claim for
      prevention of the emergence, slowing or stabilizing deterioration is strived for,
      it has to be shown that the treatment has an impact on the underlying
      neurobiology and pathophysiology of the process of dementia. Establishing such an
      effect in a highly variable progressing syndrome is complex and difficult;
      however, a variety of trial designs has been provided, including baseline
      designs, survival designs, randomized start or randomized withdrawal designs,
      with or without incorporation of biomarkers as surrogate endpoints (e.g. magnetic
      resonance tomography, emission tomography, cerebrospinal fluid markers). To be
      accepted as a surrogate endpoint such a biomarker ideally should respond to
      treatment, predict clinical response and be compellingly related to the
      pathophysiological process of the dementia. However, careful and sufficient
      validation of proposed biomarkers as a potential surrogate endpoint is a
      prerequisite for acceptance by regulatory bodies. This review outlines the
      regulatory requirements for approval of a new medicinal product for symptomatic
      improvement or disease-modifying effects in patients with dementia, with special
      emphasis on the importance of validation of the assessment tools and potential
      surrogate endpoints based on recent experience and discussion regarding anti
      dementia drugs in the European framework.

PMID- 17433122
TI  - Elder abuse and neglect in two different socioeconomic districts in Izmir,
      Turkey.
AB  - OBJECTIVE: To determine and compare the prevalence and risk factors of elder
      abuse in elderly population in two different districts in Izmir, Turkey. METHODS:
      This cross-sectional study involved 497 subjects selected by cluster sampling.
      RESULTS: The prevalence of physical and financial abuse among the elderly in the
      district of low socioeconomic status was 1.5% and 2.5%, respectively, while among
      the elderly in the district of high socioeconomic status, it was 2% and 0.3%,
      respectively. However, the prevalence of elder neglect in the two districts was
      27.4% and 11.2%, respectively. Prevalence of neglect was associated with
      infrequent contact with relatives, little or no income, and fewer years of
      education among the elderly in the low socioeconomic district. In the high
      socioeconomic district, neglect was associated with fewer years in education,
      poor health status and having chronic status. CONCLUSION: The prevalence of abuse
      among the elderly living in the two different districts was low. However, nearly
      one-fifth of elderly people were exposed to neglect.

PMID- 17433123
TI  - Estimating under-reporting of energy intake in dietary surveys using an
      individualised method.
AB  - Under-reporting (UR) of energy intake (EI) by self-reported dietary methods is
      well-documented but the methods used to estimate UR in population-based studies
      commonly assume a sedentary lifestyle. We compared estimated UR using
      individualised estimates of energy requirements with a population cut-off based
      on minimum energy needs. UR was estimated for 1551 adults aged 19-64 years
      enrolled in the National Diet and Nutrition Survey. Physical activity diaries and
      7 d weighed dietary records were completed concurrently. Mean daily EI (kJ/d) was
      calculated from the dietary records. Reported physical activity was used to
      assign each subject's activity level, and then to calculate estimated energy
      requirements (EER) from published equations. UR was calculated both as EER - EI
      with an adjustment for daily EER and EI variation, and also by a population
      method. By the individual method UR was approximately 27 % of energy needs in men
      and 29 % in women, with 75 % of men and 77 % of women classified as under
      reporters; by the population method 80 and 88 % were classified as under
      reporters respectively. When subjects who reported their eating being affected by
      dieting or illness during dietary recording were excluded, UR was 25 % of energy
      needs in both sexes. UR was higher in overweight and obese men and women compared
      with their lean counterparts (P < 0.001). UR of EI must be considered in dietary
      surveys. The EER method allows UR to be quantified and takes into account an
      individual's activity level. Measures of physical activity and questions to
      identify under-eating during dietary recording may help to evaluate secular
      trends in UR.

PMID- 17433124
TI  - Folate deficiency during pregnancy impacts on methyl metabolism without affecting
      global DNA methylation in the rat fetus.
AB  - The methionine cycle and methyl group metabolism are implicated in the long-term
      programming of metabolism. Diets deficient in folic acid, methionine and choline
      have been fed to pregnant rats to examine the effects on amino acid metabolism,
      choline reserves and DNA methylation in dam and fetuses. Animals were fed folate
      deficient, folate-deficient with low methionine, folate-deficient with low
      choline and folate-deficient, low-methionine, low-choline diets starting 2 weeks
      before mating. The dams and their fetuses were subsequently killed on day 21 of
      gestation for analysis. Diets low in methionine reduced fetal and maternal
      weight. Folate deficiency increased the concentrations of homocysteine, glycine,
      serine and threonine in the maternal plasma, and this was exacerbated by the low
      methionine diets. The changes in the amino acid profile in the fetal serum were
      similar but less pronounced. This result suggests that fetal metabolism was less
      perturbed. Folate deficiency increased free choline in the maternal liver at the
      expense of phosphocholine stores. It has been suggested that a deficiency in
      methyl donors in the diet during pregnancy may impact on key methylation
      reactions, including the methylation of DNA. Despite widespread changes in the
      metabolism of choline and amino acids, there was no change in the global
      methylation of cytosine in DNA from either maternal or fetal livers. This
      suggests a more indirect mechanism in which gene-nutrient interactions modify the
      process of differential methylation during development.

PMID- 17433125
TI  - Administration of Lactobacillus evokes coordinated changes in the intestinal
      expression profile of genes regulating energy homeostasis and immune phenotype in
      mice.
AB  - Lactic acid bacteria are probiotics widely used in functional food products, with
      a variety of beneficial effects reported. Recently, intense research has been
      carried out to provide insight into the mechanism of the action of probiotic
      bacteria. We have used gene array technology to map the pattern of changes in the
      global gene expression profile of the host caused by Lactobacillus
      administration. Affymetrix microarrays were applied to comparatively characterize
      differences in gene transcription in the distal ileum of normal microflora (NMF)
      and germ-free (GF) mice evoked by oral administration of two Lactobacillus
      strains used in fermented dairy products today - Lactobacillus paracasei ssp.
      paracasei F19 (L. F19) or Lactobacillus acidophilus NCFB 1748. We show that
      feeding either of the two strains caused very similar effects on the
      transcriptional profile of the host. Both L. F19 and L. acidophilus NCFB 1748
      evoked a complex response in the gut, reflected by differential regulation of a
      number of genes involved in essential physiological functions such as immune
      response, regulation of energy homeostasis and host defence. Notably, the changes
      in intestinal gene expression caused by Lactobacillus were different in the mice
      raised under GF v. NMF conditions, underlying the complex and dynamic nature of
      the host-commensal relationship. Differential expression of an array of genes
      described in this report evokes novel hypothesis of possible interactions between
      the probiotic bacteria and the host organism and warrants further studies to
      evaluate the functional significance of these transcriptional changes on the
      metabolic profile of the host.

PMID- 17433126
TI  - Tracking of fruit and vegetable consumption from adolescence into adulthood and
      its longitudinal association with overweight.
AB  - The objective of the present study was to assess to what extent fruit and
      vegetable intakes track over a 24-year time period and to assess longitudinal
      associations between fruit and vegetable intakes and (change in) BMI and sum of
      skinfolds. Dietary intake and anthropometrics were repeatedly assessed for 168
      men and women between the ages of 12 and 36 years. Linear general estimating
      equations analyses were applied (1) to estimate tracking coefficients, (2) to
      estimate predictability for meeting the national recommendation for fruit and
      vegetable intake and for being in the highest quartile for fruit and vegetable
      intake, and (3) to estimate the association between fruit and vegetable intake
      and BMI and sum of skinfolds. We found that tracking coefficients were 0.33 (P <
      0.001) for fruit intake and 0.27 (P < 0.001) for vegetable intake. Mean fruit
      intake decreased over a 24-year period. For fruit intake, predictability was
      higher in men than in women (OR 6.02 (P < 0.001) and 2.33 (P = 0.001) for meeting
      the recommendation for men and women respectively). After adjustment, fruit
      intake was not associated with BMI, but being in the lowest quartile of fruit
      intake was significantly associated with a lower sum of skinfolds. Women in the
      lowest quartiles of vegetable intake had significantly higher BMI and sum of
      skinfolds and also greater positive changes in these parameters. In conclusion,
      tracking and predictability for fruit and vegetable intake appear to be low to
      moderate, which might indicate that fruit and vegetable promotion should be
      started at an early age and continued into adulthood. Despite the fact that we
      only observed beneficial weight-maintaining effects of vegetable intake in women,
      promoting vegetables is important for both sexes because of other positive
      properties of vegetables. No evidence was found for promoting fruit intake as a
      means of weight maintenance.

PMID- 17433127
TI  - Empirically derived major dietary patterns and their associations with overweight
      in Korean preschool children.
AB  - Prevailing dietary patterns and their association with nutritional outcomes are
      poorly understood, particularly for children in Korea. Our purposes were to
      identify major dietary patterns and to examine their associations with overweight
      among young children in Korea. For 1441 preschool children, usual diet was
      assessed by a FFQ, from which thirty-three food groups were created and entered
      into a factor analysis. We identified three dietary patterns by relative intake
      frequency of (1) vegetables, seaweeds, beans, fruits, milk and dairy products
      (Korean healthy pattern); (2) beef, pork, poultry, fish and fast foods (animal
      foods pattern); and (3) ice cream, soda, chocolate, cookies and candies (sweets
      pattern). The Korean healthy pattern was associated with better health status. As
      compared with the lowest quintile, the multivariate-adjusted OR of the highest
      quintile for health status inferior or similar to their peers was 0.59 (95 % CI
      0.42, 0.84). Likelihood of being overweight was higher among those in the highest
      quintile (OR 1.77 (95 % CI 1.06, 2.94)) v. the lowest quintile regarding the
      animal foods pattern. These findings suggest that major dietary patterns are
      predictors of overweight and health status in Korean preschool children.

PMID- 17433128
TI  - A high oxidised frying oil content diet is less adipogenic, but induces glucose
      intolerance in rodents.
AB  - Oxidised frying oil (OFO) and fish oil have been shown to be peroxisome
      proliferator-activated receptor (PPAR)alpha activators and their ingestion
      results in pleotropic peroxisome proliferator responses in rats. To examine the
      effect of dietary OFO on adiposity, four groups of weanling Sprague-Dawley rats
      were fed isoenergetically with, respectively, a low fat basal diet containing 5
      g/100 g of fresh soybean oil (LSB) or a high fat diet containing 20 g/100 g of
      fresh soybean oil (HSB), OFO (HO) or fish oil (HF). The tissue mass, cell size
      and lipid/DNA ratio in the retroperitoneal fat pad and serum leptin levels were
      lowest in the HO group (P < 0.05), indicating that dietary OFO has a greater anti
      adipogenic action than dietary fish oil. However, a tendency to hyperglycaemia
      was observed in the HO group (P = 0.0528). To examine the effect of dietary OFO
      on glucose tolerance, three groups of rats and three groups of mice were fed,
      respectively, the LSB, HSB or HO diet, and an oral glucose tolerance test was
      performed. After oral glucose load, the area under the curve for blood glucose
      (AUCglu) over 2 h was significantly higher, and that for serum insulin (AUCins)
      over 90 min was significantly lower, in the HO group than in the other two groups
      (P < 0.05). These results demonstrate that, in rats and mice, a high OFO diet is
      less adipogenic, but induces glucose intolerance.

PMID- 17433129
TI  - Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor
      in the offspring of rats fed a protein-restricted diet during pregnancy suggests
      that reduced DNA methyltransferase-1 expression is involved in impaired DNA
      methylation and changes in histone modifications.
AB  - Prenatal nutritional constraint induces an altered metabolic phenotype in the
      offspring which in humans confers an increased risk of non-communicable disease.
      Feeding a protein-restricted (PR) diet to pregnant rats causes hypomethylation of
      specific gene promoters in the offspring and alters the phenotype. We
      investigated how altered epigenetic regulation of the hepatic glucocorticoid
      receptor (GR) 1(10) promoter is induced in the offspring. Rats were fed a control
      (180 g casein/kg) or a PR (90 g casein/kg) diet throughout pregnancy, and chow
      during lactation. Offspring were killed at postnatal day 34 (n 5 per maternal
      dietary group). Methylation-sensitive PCR showed that GR1(10) promoter
      methylation was 33 % lower (P < 0.001) and GR expression 84 % higher (P < 0.05)
      in the PR offspring. Reverse transcription-PCR showed that DNA methyltransferase
      1 (Dnmt1) expression was 17 % lower (P < 0.05) in PR offspring, while Dnmt3a/b
      and methyl binding domain protein-2 expression was not altered. Thus
      hypomethylation of the GR110 promoter may result from lower capacity to methylate
      hemimethylated DNA during mitosis. Histone modifications which facilitate
      transcription were increased at the GR1(10) promoter (147-921 %, P < 0.001),
      while those that suppress methylation were decreased (54 %, P < 0.01) or similar
      to controls. In human umbilical cord (n 15), there was a 2-fold difference
      between the highest and lowest level of GR1-CTotal promoter methylation. Dnmt1,
      but not Dnmt3a, expression predicted 49 % (P = 0.003) of the variation in GR1
      CTotal promoter methylation. These findings suggest that induction in the
      offspring of altered epigenetic regulation of the hepatic GR1(10) promoter, and
      hence metabolic phenotype, may be due to reduced Dnmt1 expression.

PMID- 17433130
TI  - Retrospective survey of Chikungunya disease in Reunion Island hospital staff.
AB  - Reunion Island (Indian Ocean) has been suffering from its first known Chikungunya
      virus (CHIKV) epidemic since February 2005. To achieve a better understanding of
      the disease, a questionnaire was drawn up for hospital staff members and their
      household. CHIKV infected about one-third of the studied population, the
      proportion increasing with age and being higher in women. Presence of a garden
      was associated with CHIKV infection. The geographical distribution of cases was
      concordant with insect vector Aedes albopictus distribution. The main clinical
      signs were arthralgia and fever. The disease evolved towards full recovery in
      34.4% of cases, a relapse in 55.6%, or a chronic form in 10%. Paracetamol was
      used as a painkiller in 95% of cases, sometimes associated with non-steroidal
      anti-inflammatory drugs, corticoids, or traditional herbal medicine. The survey
      provided valuable information on the factors that favour transmission, the
      clinical signs, the importance of relapses and the therapies used.

PMID- 17433131
TI  - Measles outbreaks affecting children in Jewish ultra-orthodox communities in
      Jerusalem.
AB  - In 2003 and 2004 two measles outbreaks occurred in Jewish ultra-orthodox
      communities in Jerusalem. The index case of the first outbreak (March 2003) was a
      2-year-old unvaccinated child from Switzerland. Within 5 months, 107 cases (mean
      age 8.3+/-7.5 years) emerged in three crowded neighbourhoods. The first cases of
      the second outbreak (June 2004) were in three girls aged 4-5 years in one
      kindergarten in another community. By November 2004, 117 cases (mean age 7.3+/
      6.5 years) occurred. The virus genotypes were D8 and D4 respectively. Altogether,
      96 households accounted for the two outbreaks, with two or more patients per
      family in 79% of cases. Most cases (91.5%) were unvaccinated. Immunization
      coverage was lower in outbreak than in non-outbreak neighbourhoods (88.3% vs.
      90.3%, P=0.001). Controlling the outbreaks necessitated a culture-sensitive
      approach, and targeted efforts increased MMR vaccine coverage (first dose) to
      95.2%. Despite high national immunization coverage (94-95%), special attention to
      specific sub-populations is essential.

PMID- 17433133
TI  - Accuracy of WHO case definition for SARS screening.

PMID- 17433132
TI  - Under-reporting of infectious gastrointestinal illness in British Columbia,
      Canada: who is counted in provincial communicable disease statistics?
AB  - Under-reporting of infectious gastrointestinal illness (IGI) in British Columbia,
      Canada was calculated using simulation modelling, accounting for the uncertainty
      and variability of input parameters. Factors affecting under-reporting were
      assessed during a cross-sectional randomized telephone survey. For every case of
      IGI reported to the province, a mean of 347 community cases occurred (5th and
      95th percentile estimates ranged from 181 to 611 community cases, respectively).
      Vomiting [odds ratio (OR) 2.15, 95% confidence interval (CI) 1.03-4.49] and
      antibiotic use in the previous 28 days (OR 3.59, 95% CI 1.17-10.97) significantly
      predicted health-care visits in a logistic regression model. In bivariate
      analyses, physicians were significantly less likely to request stool samples from
      patients with vomiting (RR 0.09, 95% CI 0.01-0.65) and patients of North American
      as opposed to non-North American cultural groups (RR 0.38, 95% CI 0.15-0.96).
      Physicians were more likely to request stool samples from older patients
      (P=0.003), patients with fewer household members (P=0.002) and those who reported
      anti-diarrhoeal use following illness (RR 3.33, 95% CI 1.32-8.45). People with
      symptoms of vomiting were under-represented in provincial communicable disease
      statistics. Differential degrees of under-reporting must be understood before
      biased surveillance data can be adjusted.

PMID- 17433135
TI  - Accuracy of WHO case definition for SARS screening.

PMID- 17433136
TI  - Case definition versus screening tool for SARS.

PMID- 17433138
TI  - Correct way to wear respirator head harnesses.

PMID- 17433137
TI  - Medical myth: the usefulness of pelvic exam.

PMID- 17433139
TI  - Pneumatosis intestinalis.

PMID- 17433140
TI  - Early clinical predictors of severe acute respiratory syndrome in the emergency
      department.
AB  - OBJECTIVES: To assess the association of diagnostic predictors available in the
      emergency department (ED) with the outcome diagnosis of severe acute respiratory
      syndrome (SARS). METHODS: This retrospective cohort study describes all patients
      from the Amoy Garden complex who presented to an ED SARS screening clinic during
      a 2-month outbreak. Clinical and diagnostic predictors were recorded, along with
      ED diagnoses. Final diagnoses were established independently based on diagnostic
      tests performed after the ED visit. Associations of key predictors with the final
      diagnosis of SARS were described. RESULTS: Of 821 patients, 205 had confirmed
      SARS, 35 undetermined SARS and 581 non-SARS. Multivariable logistic regression
      showed that the strongest predictors of SARS were abnormal chest x-ray (odds
      ratio [OR] = 17.4), subjective fever (OR = 9.7), temperature degrees >38 degrees
      C (OR = 6.4), myalgias (OR = 5.5), chills and rigors (OR = 4.0) and contact
      exposure (OR = 2.6). In a subset of 176 patients who had a complete blood cell
      count performed, the strongest predictors were temperature >or=38 degrees C (OR =
      15.5), lymphocyte count <1000 (OR = 9.3) and abnormal chest x-ray (OR = 5.7).
      Diarrhea was a powerful negative predictor (OR = 0.03) of SARS. CONCLUSIONS: Two
      components of the World Health Organization case definition - fever and contact
      exposure - are helpful for ED decision-making, but respiratory symptoms do not
      discriminate well between SARS and non-SARS. Emergency physicians should consider
      the presence of diarrhea, chest x-ray findings, the absolute lymphocyte count and
      the platelet count as significant modifiers of disease likelihood. Prospective
      validation of these findings in other clinical settings is desirable.

PMID- 17433141
TI  - Can troponin I measurement predict short-term serious cardiac outcomes in
      patients presenting to the emergency department with possible acute coronary
      syndrome?
AB  - OBJECTIVE: To determine the ability of troponin I (TnI) measurement to predict
      the likelihood of a serious cardiac outcome over the subsequent 72 hours in
      patients presenting to the emergency department (ED) with symptoms suggestive of
      an acute coronary syndrome. METHODS: This prospective observational study
      enrolled consecutive patients presenting to 2 urban tertiary care hospital EDs
      over a 5-week period. Eligible patients included those for whom a TnI test was
      ordered within 24 hours of arrival and in whom no serious cardiac outcome
      occurred before the test result was available. Patients were followed for 72
      hours and serious cardiac outcomes documented; these included cardiovascular
      death, myocardial infarction, congestive heart failure, serious arrhythmia and
      refractory pain. We calculated likelihood ratios (LRs) to describe the
      association of the TnI result with serious cardiac outcomes. RESULTS: Of the 352
      enrolled patients, 20 had a serious cardiac outcome within 72 hours of ED
      presentation. The derived LRs (and 95% confidence interval [CI]) were 0.5 (0.3
      0.9) for TnI values <0.5 microg/L, 1.6 (0.4-6.5) for TnI values from 0.5 to 2.0
      microg/L, 5.8 (1.7-19.5) for TnI values from >2.0 to 10.0 microg/L and 14.4 (4.8
      42.9) for TnI values >10.0 microg/L. CONCLUSIONS: TnI values >2.0 microg/L are
      associated with an increased probability of serious cardiac outcomes within 72
      hours. TnI values between 0.5 and 2.0 microg/L are weakly positive predictors.
      TnI values <0.5 microg/L have LRs in the range of 0.5 and thus are weakly
      negative predictors, not substantially decreasing the likelihood of serious
      cardiac outcomes, particularly in patients with a moderate or high pretest
      probability.

PMID- 17433142
TI  - War on SARS: a Singapore experience.
AB  - On Mar. 12, 2003, the World Health Organization issued a global alert regarding
      cases of a severe atypical pneumonia termed "severe acute respiratory syndrome"
      (or SARS). In Singapore alone, there have been 238 SARS cases and 33 deaths,
      including 5 health care workers. With modern global inter-connectivity, SARS
      rapidly spread to become a worldwide phenomenon. This article describes the
      Singapore "war on SARS" from an emergency physician's perspective, focusing on
      the "prevent, detect and isolate" strategy. Notable innovations include the use
      of home quarantine orders, mass temperature screening using thermal imaging,
      modular systems of hospital staffing, "virtual" hospital visits, and innovations
      in emergency department design. Most emergency departments, hospitals and health
      care systems appear to be psychologically and logistically unprepared for a
      massive infectious disease outbreak. In light of recent natural and terrorism
      related threats, emergency care providers around the world must adopt a new
      paradigm. The current SARS outbreak may be merely a taste of things to come.

PMID- 17433143
TI  - Intimate partner violence against women: to screen or not to screen in the
      emergency department?

PMID- 17433144
TI  - Paradoxical embolism: a rare life- and limb-threatening emergency.
AB  - This article presents a case of a 43-year-old man with paradoxical embolism. The
      patient had simultaneous deep venous thrombosis, pulmonary embolism and bilateral
      limb-threatening arterial occlusions. The unifying diagnosis was paradoxical
      embolism through a previously undetected atrial septal defect. Suggestions for
      the evaluation and emergency management of paradoxical embolism are outlined, and
      the literature is briefly reviewed.

PMID- 17433145
TI  - Potential error in the use of an automated external defibrillator during an in
      flight medical emergency.
AB  - In-flight medical emergencies are uncommon, generally non-lethal events. In fatal
      cases, the most common cause of death is a sudden cardiac event. This fact, and
      the awareness that early defibrillation is the most important determinant of
      successful cardiac resuscitation, have led to the increasing availability of
      automated external defibrillators (AEDs) aboard commercial airplanes. AEDs are
      sophisticated and extremely reliable devices that are designed to be used by
      trained laypersons in the hope of minimizing the crucial time to defibrillation.
      Although designed to be foolproof, both machine- and operator-dependent usage
      errors have been recognized. In this case study we report a unique operator
      dependent error involving the misreading of an AED instruction window, briefly
      review the history of AED use in the airline industry, and underscore the need
      for a sound knowledge of basic life support skills when working with these
      devices. We conclude by making recommendations to prevent similar errors from
      occurring in the future.

PMID- 17433146
TI  - Myth: the Trendelenburg position improves circulation in cases of shock.

PMID- 17433148
TI  - Playing the game: a four-year quest to become an emergency resident.

PMID- 17433147
TI  - A pain in the neck.

PMID- 17433149
TI  - Becoming an emergency resident: a program director's perspective.

PMID- 17433150
TI  - A Christmas hymn.

PMID- 17433152
TI  - Considering air embolism.

PMID- 17433153
TI  - Potential error in the use of AEDs during an in-flight emergency.

PMID- 17433154
TI  - Role of SARS screening clinic in the ED.

PMID- 17433155
TI  - Waiting Room medicine.

PMID- 17433156
TI  - Proportion of injured alcohol-impaired drivers subsequently convicted of an
      impaired driving criminal code offence in British Columbia.
AB  - BACKGROUND: Alcohol is a frequent contributing factor to motor vehicle collision
      injuries. Our objective was to determine the proportion of intoxicated drivers
      hospitalized following motor vehicle crashes who were subsequently convicted of
      an impaired driving criminal code offence. METHODS: We reviewed British Columbia
      Trauma Registry records from Jan. 1, 1992, to Mar. 31, 2000, and identified
      drivers of motor vehicles who were hospitalized for treatment of crash-related
      injuries. Patient identifiers were then used to link with the Insurance
      Corporation of British Columbia's (ICBC) contraventions database and the ICBC
      Traffic Accident System collisions database. RESULTS: Of 6067 patients identified
      in the Trauma Registry, 4042 had not been administered a blood ethanol test, 209
      had no driver's licence match in the relevant databases and 119 died, leaving
      1697 eligible patients. Mean age was 34 years, and 79.6% were male. The average
      Injury Severity Score was 20, the average hospital stay was 14 days and, among
      ethanol-positive patients, the mean ethanol level was 34.0 mmol/L (156.4 mg/dL).
      In patients with levels >17.3 mmol/L, the police had listed ethanol as a
      contributing factor in 70.6% of cases. Despite this, only 11.0% were convicted of
      impaired driving and 8.4% of another criminal offence; 10.7% received a 24-hour
      roadside prohibition, 3.9% received a 90-day administrative driving prohibition
      and 25.0% were convicted of a contravention of the Motor Vehicle Act. Forty-one
      percent were not convicted of any offence at all. CONCLUSIONS: Intoxicated
      drivers in British Columbia requiring hospitalization as a result of alcohol
      related motor vehicle crashes are seldom convicted of impaired driving or other
      criminal code offences.

PMID- 17433157
TI  - Sentinel surveillance of HIV and hepatitis C virus in two urban emergency
      departments.
AB  - OBJECTIVES: This study was designed to determine the prevalence of HIV and
      hepatitis C virus (HCV) in a specific population, and to distinguish between
      known and previously unrecognized infections in the emergency department (ED)
      setting. METHODS: Consecutive patients aged 15 to 54 years who had presented to
      the EDs of 2 urban hospitals during a 6-week period were enrolled in a
      prospective cross-sectional study if a complete blood count had been obtained as
      part of their care. The study patients were initially cross-referenced against
      local databases of known HIV and HCV seropositive patients. After removal of all
      personal identifiers, the study patients' leftover blood was serotested for HIV
      and HCV, and seroprevalences were calculated. Univariate and multivariate
      analyses were performed to identify factors associated with HIV and HCV
      infection. RESULTS: Of 3057 individuals whose files were analyzed, 1457 (48%)
      were male and 7% (213) were Aboriginal. Overall, 302 patients (10%; 95%
      confidence interval [CI], 9%-11%) were seropositive for HCV and, of these, only
      132 (44%) were previously known to be. HCV seropositivity was associated with
      Aboriginal status, age, male gender, hospital site and HIV infection (all p <
      0.001). In contrast, 39 patients (1%; 95% CI, 1%-2%) were HIV seropositive. Of
      these, 32 (82%) were previously known to be HIV positive, and 27 (69%) were HCV
      seropositive. HIV seropositivity was only associated with HCV infection (p <
      0.001). CONCLUSIONS: The rate of previously undetected infections was relatively
      low for HIV but high for HCV. Emergency physicians in urban settings will
      frequently encounter patients not known to be HCV positive and not identified as
      such. These results emphasize the need for more effective preventive measures in
      the community and the importance of observing standard (universal) precautions in
      ED practice.

PMID- 17433158
TI  - Utility of follow-up recommendations for patients discharged with community
      acquired pneumonia.
AB  - INTRODUCTION: The joint Canadian Infectious Diseases Society and Canadian
      Thoracic Society guidelines for community-acquired pneumonia (CAP) recommend 48
      72 hour telephone follow-up of patients discharged from the emergency department
      (ED). The guidelines provide no evidence supporting this practice, and neither
      the clinical utility nor the effectiveness of such recommendations has been
      assessed. Our objective was to assess the utility of a 48-72 hour telephone
      follow-up protocol for patients discharged from the ED with CAP. METHODS: This
      was a retrospective chart audit covering a 2-year period (Jan. 3, 1999 to Jan. 3,
      2001) after the introduction of a clinical practice guideline (CPG) that included
      routine 48-72 hour telephone follow-up of patients discharged from the ED with
      CAP. Eligible patients were identified in the ED database, rates of referral for
      telephone follow-up were recorded, and 30-day outcomes (death and readmission)
      for patients referred versus not referred were compared. RESULTS: During the
      study period, 867 patients were identified as being eligible for the study. The
      mean age was 55.7 years (range 16-98 yr), and mean pneumonia severity index (PSI)
      was 68.9 (range 6-187). Despite the CPG, only 148 patients (17.1%) were referred
      for telephone follow-up. Age, demographics, comorbidity, clinical status and
      pneumonia severity were similar for referred and non-referred patients. Thirty
      day death (2.5%) and readmission rates (3%) were strongly related to PSI score,
      but did not differ significantly in the 2 comparison groups. CONCLUSION: In this
      setting, physicians were poorly compliant with a routine telephone follow-up
      protocol. The likelihood of referral for follow-up did not correlate with
      pneumonia severity, and follow-up referral did not appear to affect patient
      outcome. These findings do not support recommendations for routine early follow
      up mechanisms beyond those already existing in the community.

PMID- 17433159
TI  - Screening urine for drugs of abuse in the emergency department: do test results
      affect physicians' patient care decisions?
AB  - BACKGROUND: Drug abuse is a frequent factor in emergency department (ED) visits.
      Although commonly performed, qualitative testing of urine for drugs of abuse (u
      DOA) is inherently limited in its ability to establish the identity, timing or
      dose of substances used. Previous studies have demonstrated these limitations,
      but their designs cannot be used to determine whether the results of u-DOA tests
      affect physicians' patient care decisions. Our objective was to determine the
      impact of u-DOA testing on the care of patients who present to the ED. METHODS:
      All adults 18 years of age or older who had u-DOA testing in 2 urban teaching EDs
      were eligible. Victims of vehicular trauma or sexual assault were excluded. Just
      prior to communicating the results of u-DOA testing for a patient, an
      investigator interviewed the ordering physician or consultant physician about the
      patient care plans for that patient. Test results were then revealed, and the
      questions immediately repeated. This design isolated the impact of knowledge of u
      DOA test results on physicians' patient care decisions. Any intended changes in
      patient care plans reported by the interviewed physician were compared to a
      priori criteria for substantive change and then subsequently reviewed by an
      independent expert to determine whether that change was justified. RESULTS: Of
      the 110 u-DOA test results studied and the resultant 133 opportunities to
      influence physician management plans, there were 4 reported changes in
      management. One management change was judged to be substantive, but none of the 4
      reported changes were considered by the independent expert reviewer to be
      justified. Urine-DOA testing thus led to a justified change in management in
      0/133 instances (95% confidence interval 0%-2.3%). CONCLUSIONS: Urine-DOA is
      rarely helpful in guiding patient care decisions in the ED. The results of this
      study call into question the need for this test in the ED setting.

PMID- 17433160
TI  - Need for bedside emergency department ultrasonography: case report of a ruptured
      ectopic pregnancy.
AB  - Ultrasonography is a useful tool for the immediate evaluation of patients with
      suspected ruptured ectopic pregnancy, abdominal aortic aneurysm, traumatic intra
      abdominal hemorrhage or cardiac tamponade. The 1999 Canadian Association of
      Emergency Physicians position statement states that bedside emergency department
      ultrasonography should be available 24 hours per day. This case study illustrates
      how emergency physicians properly trained in emergency bedside ultrasonography
      can use this tool effectively to dramatically impact patient care.

PMID- 17433161
TI  - Root cause analysis of laboratory turnaround times for patients in the emergency
      department.
AB  - INTRODUCTION: Laboratory investigations are essential to patient care and are
      conducted routinely in emergency departments (EDs). This study reports the
      turnaround times at an academic, tertiary care ED, using root cause analysis to
      identify potential areas of improvement. Our objectives were to compare the
      laboratory turnaround times with established benchmarks and identify root causes
      for delays. METHODS: Turnaround and process event times for a consecutive sample
      of hemoglobin and potassium measurements were recorded during an 8-day study
      period using synchronized time stamps. A log transformation (ln [minutes + 1])
      was performed to normalize the time data, which were then compared with
      established benchmarks using one-sample t tests. RESULTS: The turnaround time for
      hemoglobin was significantly less than the established benchmark (n = 140, t = 
      5.69, p < 0.001) and that of potassium was significantly greater (n = 121, t =
      12.65, p < 0.001). The hemolysis rate was 5.8%, with 0.017% of samples needing
      recollection. Causes of delays included order-processing time, a high proportion
      (43%) of tests performed on patients who had been admitted but were still in the
      ED waiting for a bed, and excessive laboratory process times for potassium.
      CONCLUSIONS: The turnaround time for hemoglobin (18 min) met the established
      benchmark, but that for potassium (49 min) did not. Root causes for delay were
      order-processing time, excessive queue and instrument times for potassium and
      volume of tests for admitted patients. Further study of these identified causes
      of delays is required to see whether laboratory TATs can be reduced.

PMID- 17433162
TI  - When the MAGIC stops: magnesium in acute coronary syndromes--a lesson in medical
      humility.
AB  - There has been much debate as to whether magnesium, a well-tolerated, readily
      available and cheap therapy, should be used to treat patients with suspected
      myocardial infarction. Despite promising results from animal studies and small
      clinical trials conducted in the 1980s, two large recent trials have concluded
      that the once phenomenal treatment is ineffective. The story of magnesium for
      acute myocardial infarction is a lesson in medical humility.

PMID- 17433163
TI  - Blunt traumatic rupture of the pericardium with cardiac herniation.
AB  - Traumatic rupture of the pericardium with cardiac herniation is rare. Clinicians
      are often unfamiliar with the clinical and radiological manifestations of the
      injury, and the diagnosis is frequently missed preoperatively. This case report
      describes a patient with multiple trauma following a fall from a height, who
      developed this injury. The diagnosis was not made preoperatively despite
      suggestive clinical, electrocardiographic and radiological findings. Clinicians
      need to be aware of the presentation of this potentially fatal injury so that the
      diagnosis can be made and treatment instituted at an earlier stage. Pericardial
      rupture with cardiac herniation presents as cardiogenic shock, mimicking cardiac
      tamponade.

PMID- 17433164
TI  - Sick lady.

PMID- 17433166
TI  - Acute compartment syndrome: how long before muscle necrosis occurs?
AB  - OBJECTIVES: Acute compartment syndrome (ACS) is a limb-threatening condition
      often first diagnosed by emergency physicians. Little is known about the rapidity
      with which permanent damage may occur. Our objective was to estimate the time to
      muscle necrosis in patients with ACS. METHODS: This historical cohort analysis of
      all patients who had a fasciotomy for ACS was conducted in 4 large teaching
      hospitals. Diagnosis was confirmed clinically or by needle measurement of
      compartment pressure. Muscle necrosis was determined using pathology reports and
      surgeons' operative protocols. We used descriptive statistics and estimated
      tissue survival probability using the Vertex exchange method for interval
      censored data. RESULTS: Between 1989 and 1997 there were 76 cases of ACS. Most
      cases occurred in young men (median age 32) as a result of a traumatic incident
      (82%). Forty-nine percent (37/76) of all patients suffered some level of muscle
      necrosis, and 30% (11/37) of those with necrosis lost more than 25% of the muscle
      belly. Necrosis occurred in 2 of 4 cases in which the patient had been operated
      on within 3 hours of the injury, and our exploratory survival analysis estimates
      that 37% (95% confidence interval, 13%-51%) of all cases of ACS may develop
      muscle necrosis within 3 hours of the injury. CONCLUSIONS: This is the largest
      cohort of ACS and the first clinical estimation of time to muscle necrosis ever
      published. Ischemia from ACS can cause muscle necrosis before the 3-hour period
      post-trauma that is traditionally considered safe. Further research to identify
      risk factors associated with the development of early necrosis is necessary.

PMID- 17433167
TI  - Cardioversion of uncomplicated paroxysmal atrial fibrillation: a survey of
      practice by Canadian emergency physicians.
AB  - OBJECTIVE: Paroxysmal atrial fibrillation (PAF) is the rhythm disturbance most
      commonly encountered by emergency physicians, yet the role played by emergency
      physicians in the management of this condition has not been well described. The
      purpose of this study was to describe the management of uncomplicated PAF by
      Canadian emergency physicians. METHODS: All members of the Canadian Association
      of Emergency Physicians with a Canadian address (n = 1255) were mailed a 15-point
      questionnaire regarding training/certification, hospital demographics and
      practice patterns regarding the management of uncomplicated PAF. Chi-squared
      analysis and Fisher's Exact test were performed to identify significant
      differences in reported practice patterns in relation to demographic variables.
      Significant associations were tested for interaction using the Mantel-Haenszel
      test. RESULTS: We received 663 responses, representing a 52.8% response rate. Six
      hundred and twenty-two (95%), 514 (78%) and 242 (38%) respondents reported
      routine performance of rate control, chemical cardioversion and electrical
      cardioversion respectively. Physicians working in high-volume emergency
      departments (>50,000 visits/yr) were significantly more likely to self-manage
      rate control and chemical/electrical cardioversion than those working in lower
      volume emergency departments. Residency training was associated with higher
      performance of electrical (44% v. 31%, p < 0.01) but not chemical cardioversion
      or rate control, although, amongst residency trained physicians, those with FRCP
      level training were significantly more likely to perform both chemical (86% v.
      76%, p < 0.05) and electrical (57% v. 37%, p < 0.01) cardioversion. CONCLUSION:
      Canadian emergency physicians surveyed in this study actively manage
      uncomplicated PAF. We found significant variations in practice, especially
      related to the use of electrical cardioversion. This may reflect different
      practice environments, levels of training, and lack of evidence to guide best
      practice. Further research is required to determine the optimal care of PAF in
      the emergency department setting.

PMID- 17433168
TI  - Can nurses apply the Canadian C-Spine Rule? A pilot study.
AB  - OBJECTIVE: The aim of this study was to determine the inter-rater agreement
      between physicians and nurses regarding eligibility for application of the
      Canadian C-Spine Rule (CCR) and assessment of the criteria of the CCR. METHODS:
      In this observational study, nurses and physicians independently assessed the CCR
      criteria in a convenience sample of patients with potential C-spine injury. Data
      were entered onto separate data sheets. The outcomes of interest were the inter
      rater agreement between nurse and physician regarding eligibility for application
      of the rule, for assessment of each component of the rule and for interpretation
      of the rule overall, assessed by kappa analysis. RESULTS: In total, 88 cases were
      eligible for analysis. Physicians and nurses agreed on which patients were
      eligible for CCR application in 96.6% of cases. Inter-rater agreement for most
      CCR criteria was good (* > 0.61), with the exception of midline tenderness (* =
      0.58) and range of motion, which most nurses did not test. CONCLUSION: This study
      shows that nurses have the potential to reliably apply the Canadian C-Spine Rule
      but require further training in the assessment of midline tenderness and range of
      motion.

PMID- 17433169
TI  - Heterogeneity, evidence and salt.

PMID- 17433170
TI  - Delayed diagnosis of splenic rupture following minor trauma: beware of comorbid
      conditions.
AB  - Although rare, spontaneous splenic rupture has been reported in cases of chronic
      lymphocytic leukemia (CLL). In contrast, there are no published reports of
      splenic injury resulting from minor trauma in CLL patients. We report the case of
      an 81-year-old woman with a history of CLL, who presented with minor trauma to
      her coccygeal region, and was found to have a splenic rupture. We briefly
      describe the incidence, pathogenesis, presentation, diagnosis, management and
      prognosis of splenic injury, especially in cases with a history of splenomegaly.

PMID- 17433172
TI  - Professor Ante Vukas (1910-1991) - always ahead of his time.
AB  - The biography of Professor Ante Vukas, MD, PhD, is accompanied by due account of
      his professional and organizing competences, at first as head of the Department
      of Dermatology and Venereology, Susak Hospital, later head of the University
      Department at the same hospital, introducing the latest methods in the diagnosis
      and therapy of skin and venereal diseases (epidermotectoscopy, corrective
      dermatology, immunotherapy, electron microscopy, immunohistology, PUVA therapy,
      etc.). Although all these methods were introduced at the institution headed by
      Professor Vukas first in the former state, and some of them even first in Europe,
      he had never received any formal recognition of his professional and scientific
      work from either his University Hospital, or School of Medicine where he was also
      employed, or the city where he worked for more than 40 years. Professor Vukas was
      a proud man, standing these insults with dignity, steadily keeping his feelings
      about them as well as his own achievements to himself.

PMID- 17433173
TI  - Treatment of vitiligo with narrow-band UVB and topical gel containing catalase
      and superoxide dismutase.
AB  - Narrow-band UVB has been reported to be efficacious in patients with vitiligo.
      The epidermis of patients with vitiligo showed reduction in the levels of
      catalase, in association with high levels of hydrogen peroxidase (H2O2) that is
      toxic for melanocytes. Based on these findings, we studied the efficacy and
      safety of a topical gel containing catalase and superoxide dismutase (Vitix) in
      combination with narrow-band UVB. The study included 22 patients of which 19
      completed the 6-month study period. Patients applied the gel containing catalase
      and superoxide dismutase twice a day and received narrow-band UVB 3 times per
      week. Two different dermatologists evaluated the grade of repigmentation by
      photograph comparison. At the end of therapy, more than 50% of overall
      repigmentation was noticed in 11 of 19 (57.9%) patients. More than 75%
      repigmentation was recorded in three (15.79%), 26%-50% repigmentation in six
      (31.58%) patients and 1%-25% repigmentation in one (5.26%) patient, whereas one
      (5.26%) of 19 patients showed no repigmentation at all. The best response was
      achieved on the face and neck, with more than 50% repigmentation observed in 11
      of 14 (78.6%) patients. Development of new lesions was not observed. Adverse
      events were mild and transient. The study showed that the combination therapy of
      narrow-band UVB and gel containing catalase and dismutase is a therapeutic option
      that could be considered in the management of vitiligo. Further evaluation of
      this combination in multicenter, double-blind, placebo-controlled studies should
      be undertaken.

PMID- 17433175
TI  - Epidermolytic hyperkeratosis type NPS-3: a case report.
AB  - Epidermolytic hyperkeratosis (EHK) or bullous congenital ichthyosiform
      erythroderma is a rare autosomal dominant disorder characterized by an early
      onset, with erythroderma and bullous lesions, leading to severe generalized
      hyperkeratosis in adulthood. Mutations have been found in keratin 1 and keratin
      10 genes. The clinical manifestations of EHK present striking heterogeneity and
      at least six clinical phenotypes have been identified. We report on a case of EHK
      in a 12-year-old girl with erythroderma, erosions and blisters on the entire body
      surface at birth and generalized hyperkeratosis but without severe palm and sole
      involvement in the later stage. On the basis of clinical and histopathologic
      findings, the diagnosis of EHK type NPS-3 was made.

PMID- 17433174
TI  - Naphthalene in the treatment of patients with atopic dermatitis.
AB  - Atopic dermatitis is a chronic relapsing inflammatory skin disease the incidence
      of which has been constantly growing in all age groups. Research into the use of
      naphthalene in the treatment of patients with psoriasis proved its anti
      inflammatory and antiproliferative effects as well as a satisfactory remission
      for months in more than 70% of treated patients with psoriasis. The present study
      was undertaken to investigate the efficacy of naphthalene in the treatment of
      patients with atopic dermatitis. According to study results, naphthalene therapy
      proved efficacious and free from side effects in 20 atopic dermatitis patients.

PMID- 17433176
TI  - Regressing seborrheic keratosis - clinically and dermoscopically mimicking a
      regressing melanoma.
AB  - The diagnosis of seborrheic keratosis is a clinical diagnosis. In a certain
      percentage of cases, differential diagnosis between seborrheic keratosis and
      malignant melanoma is difficult. We describe a case of regressing seborrheic
      keratosis simulating malignant melanoma. Clinical, dermoscopic and
      histopathologic examinations were performed for the occurrence of an asymmetric,
      irregularly demarcated, irregularly pigmented lesion measuring 1.3 x 1.5 cm on
      the right part of the abdomen in a 76-year-old male Caucasian. In order not to
      miss melanoma, the excision and histopathologic examination of the lesion with
      peppering is essential.

PMID- 17433177
TI  - Normalization in the appearance of severly damaged psoriatic nails using soft x
      rays. A case report.
AB  - The prevalence of nail psoriasis varies considerably among different studies,
      ranging from 10% to 55%. In psoriatic arthritis, its prevalence is as high as
      85%. In spite of the high prevalence of the disease, considerable functional,
      psychical and cosmetic discomforts for the affected patients, and recent advances
      in the management of skin psoriasis, an efficacious and longlasting treatment for
      psoriatic nails remains elusive. A 51-year-old male patient with skin psoriasis
      and severe psoriatic lesions of all his finger nails and toe nails is presented.
      Some nail plates were up to 30 times thicker than normal. The patient received
      radiotherapy with soft x-rays in a total dose of 13.5 Gy administered in nine
      fractionated doses of 1.5 Gy (43 kV, 25 mA, 0.6 mm aluminum filter) at one-week
      and two-week intervals. Upon therapy completion, the appearance of nail plates
      gradually improved to normalize completely at 12 months of therapy. Almost three
      years of therapy completion, the patient is free from both disease relapse and
      radiotherapy sequels. Considering the high therapeutic efficacy and longlasting
      remission achieved, this type of radiotherapy should be used in the treatment of
      severe psoriatic nail lesions with massive nail plate thickening, to alleviate
      psychical and functional difficulties associated with the disease.

PMID- 17433178
TI  - Pediculosis corporis: an ancient itch.
AB  - Lice are obligatory parasites surviving on blood meals obtained from the host,
      with their mouthparts modified to enable piercing and sucking. The infestation
      with body lice, also known as pediculosis corporis, is a common worldwide problem
      that affects people of all races. Body lice are preferentially seen in cold
      climates, under conditions of poor sanitation and crowding. Pediculosis corporis
      is not only a disease in itself, but it can also be a source of bacterial
      infections. The hallmark of pediculosis corporis is pruritus and pyoderma of
      clothing covered areas. A more general reaction of fever, headaches, a diffuse
      rash, fatigue, and myalgias may appear a few weeks or months after the beginning
      of the parasitism. Treatment is comprised of improved hygiene and laundering of
      all the infested clothing, bedding and linens in hot water. Medical treatment
      involving pediculicides is required in large-scale infestations.

PMID- 17433179
TI  - Thalidomide and its dermatologic uses.
AB  - Thalidomide is a beneficial agent for treating a variety of refractory
      dermatologic disorders including erythema nodosom leprosum, lupus erythematosus,
      prurigo nodularis, actinic prurigo, pyoderma gangrenosum and aphthous stomatitis.
      Two thalidomide analogues, lenalidomide and CC-4047, are considerably more potent
      with decreased side effects when compared to thalidomide. They are currently
      undergoing trials and show promise, as they have increased immunomodulatory and
      anti-angiogenic activity. This category of medication and its use will be
      reviewed.

PMID- 17433180
TI  - What should be used as tools in women at risk of autoimmune disease?

PMID- 17433181
TI  - Bacitracin contact allergy in Zagreb.

PMID- 17433182
TI  - [Satisfaction survey administered to the relatives of critical patients].
AB  - OBJECTIVE: To know the family needs of patients admitted to our Intensive Care
      Unit (ICU). DESIGN: Prospective, descriptive study performed over a 6-month
      period. SETTING: ICU of the Insular University Hospital in Gran Canary Islands.
      PARTICIPANTS: Adult patients admitted to the ICU for more than 48 hours who were
      discharged to the hospitalization ward. INTERVENTION: A modified Society of
      Critical Care Medicine Family Needs Assessment instrument was administered to the
      first-degree relatives of patients after discharge by face-to-face interviews by
      not-informing personnel. MAIN VARIABLES: Data were gathered on demographic
      information on the patients and their interviewed relatives, reason for
      admission, and evaluation on information, care, empathy with the personnel and
      comfort. RESULTS: Family members of 99 patients were interviewed. A total of 80%
      of those interviewed considered the information had been in terms that they could
      understand, that they understood what was happening to the patient and why things
      were being done. However, 74% answered that the personnel had never explained the
      equipment being used. About 90% thought that they had received sincere
      information and that adequate care was being given. Considering empathy with the
      personnel, almost all considered they were nice but that 73% of them had never
      been asked if they needed anything. A total of 85% of them were sure that someone
      would phone them if there was any significant change in their relative's
      condition, and they felt comfortable during the time of visit; 74% did not feel
      alone or isolation. CONCLUSIONS: Most family members were highly satisfied with
      the care provided to them and their relatives in the intensive care unit, but the
      need to improve some aspects of the communication with families was identified.

PMID- 17433183
TI  - [Allocation of resources in patients with bad prognosis: the need for debate].
AB  - OBJECTIVE: Assess the opinion of health care professions on the awarding of
      resources when the patient has a bad prognosis. DESIGN: Survey type test where a
      scenario of a patient with a 6 month life prognosis is posed, differentiating
      between good and bad quality of life. It is evaluated if the following resources
      would be indicated if necessary: admission to ICU, hemodialysis, hip prosthesis,
      transplant, Hospital admission, antibiotics for bacterial infection, permanent
      pacemaker and surgery. To analyze the possible association between the variables,
      the Pearson's Chi Square Test or that of linear tendency was used. To determine
      if each person interviewed was appropriate in a different way based on the
      patient's quality of life status, the McNemar test was used. SETTING: University
      Hospital of 480 beds. PARTICIPANTS: Sample of 256 volunteers (physicians and
      nurses) from the Emergency Service, Intensive Care Unit and Operating Room.
      INTERVENTIONS: A responsible physician was in charge of personally distributing
      the survey during a 2-week period and to explain the possible doubts that could
      arise on it. RESULTS: A total of 23.8% of those surveyed considered that
      transplant would be indicated and 79.8% that permanent pacemaker would be
      indicated if the patient had a good quality of life. If there was bad quality of
      life, 9.1% would have always indicated hemodialysis (60.5% never), 2.8% hip
      prosthesis (81.1% never) and 4% complex surgery (78.8% never). There were also
      significant differences in all the variables studied, depending on whether the
      patient had good or bad quality of life. CONCLUSION: There is great variability
      on the allotment of resources for patients with limited possibilities of
      survival.

PMID- 17433184
TI  - [Limitation of therapeutic effort after ICU admission. Analysis of related
      factors].
AB  - OBJECTIVE: To analyze the limitation of therapeutic effort (LTE) in our Intensive
      Care Unit (ICU) and the variables associated with that decision. DESIGN:
      Prospective cohort study with a follow up of one year after discharge. SETTING:
      ICU of a second level hospital. PATIENTS: Four hundred and nine patients admitted
      during a two-year period. MAIN VARIABLES: APACHE II, NEMS, SOFA, quality of life
      (PAEEC) and mortality. RESULTS: LTE was performed in 49 (12%) patients. This
      decision was made by general agreement among the care team in 88% of cases and
      with the family in 73.5%. It was made on day 8 (4-20) with a SOFA score of 9 (4
      13). Mortality in the LTE group was 69.4% in ICU, 92% in hospital, and 96% at 6
      and 12 months. A logistic regression model showed that the variables associated
      with LTE were the following: NEMS score >or=30.7 (OR 12; 95% CI 3.7-39, p <
      0.001), NEMS 26.6-30.6 (OR 8; 95% CI 2.5-25.6, p = 0.001), APACHE II > 30 (OR
      7.6; 95% CI 2-29, p = 0.003), quality of life >or= 7 (OR 4.2; 95% CI 1.1-15, p =
      0.03), age >or= 80 (OR 3.7, 95% CI 1.4-9.5, p = 0.007) and medical patient
      condition (OR 3.5; 95% CI 1.5-8, p = 0.003). CONCLUSIONS: LTE is a common
      practice and is usually performed among the care team and the patient's
      surrogates. The main variables associated with LSC are those related to the
      severity of illness, previous quality of life, medical disease and patient's age.

PMID- 17433185
TI  - [Molecular and biophysical mechanisms and modulation of ventilator-induced lung
      injury].
AB  - Ventilator-induced lung injury (VILI) is associated to a high rate of mortality
      with an important social impact. Mechanical ventilation induces structural and
      ultrastructural alterations in all cell types of the lung and can derive in the
      transduction of intracellular signals, as well as in changes in the expression of
      genes, a process known as mechanotransduction. Some of the conditions involved,
      such as inflammation and/or coagulation, apoptosis/necrosis can lead to the
      propagation of the injury outside the lung, resulting in multiorganic failure.
      VILI can be modulated by means of diverse interventions as the use of protective
      ventilatory modes, therapeutic approaches based on vasoactive and antioxidative
      drugs, and more recently treatments based on the use of repairing substances of
      the surfactant like poloxamers among others. Knowledge of the mechanisms involved
      in VILI is definitive for a better approach to this condition.

PMID- 17433186
TI  - [Pseudomonas aeruginosa: combined treatment vs. monotherapy].
AB  - Pseudomonas aeruginosa is a pathogen commonly encountered in clinical practice in
      critically ill patients. It is a serious cause of infection, associated with a
      high rate of morbidity and mortality. Inappropriate antimicrobial therapy and
      delay in starting effective antimicrobial therapy is associated with worse
      prognostic. This microorganism is clinically indistinguishable from others forms
      of gram-negative bacterial infection. The rate of multidrug-resistant P.
      aeruginosa has increased in the last years. For these reasons, patients with
      Pseudomonas infection might receive empirical antibiotics that are inactive
      against Pseudomonas, especially before antibiotic susceptibility results become
      available. It remains controversial whether combination therapy, given
      empirically or as definitive treatment, for suspected Pseudomonas aeruginosa
      infections is justifiable. In the present article, we aimed to review recent
      studies that have evaluated the impact of combination therapy on Pseudomonas
      infections outcome and we exhibit our point of view in this subject. It seems
      justifiable to start combination therapy with two antipseudomonal agents in
      patients with risk for Pseudomonas infection during the first 3-5 days, until
      having microbiological results. This combination therapy must be changed to
      monotherapy on the basis on the specific susceptibility pattern of the initial
      isolate. In cases without microbiological diagnosis and poor outcome, combination
      therapy will be maintained and other causes of infection will be studied.
      Multicentre prospective randomized trials in critically ill patients are needed
      to determine which antimicrobials combinations improve outcome in Pseudomonas
      infections.

PMID- 17433187
TI  - Current insights in intra-abdominal hypertension and abdominal compartment
      syndrome.
AB  - A compartment syndrome exists when increased pressure in a closed anatomic space
      threatens the viability of the tissue within the compartment. When this occurs in
      the abdominal cavity it threatens not only the function of the intra-abdominal
      organs, but it can have a devastating effect on distant organs as well. Recent
      animal and human data suggest that the adverse effects of elevated intra
      abdominal pressure (IAP) can occur at lower levels than previously thought and
      even before the development of clinically overt abdominal compartment syndrome
      (ACS). The ACS is not a disease but truly a syndrome, a spectrum of symptoms and
      signs that can and mostly does have multiple causes. It is only recently that
      this condition received a heightened awareness. This article reflects the current
      state of knowledge on intra-abdominal pressure regarding etiology, epidemiology,
      diagnosis, IAP measurement, organ dysfunction, prevention and treatment.

PMID- 17433188
TI  - [Lethal streptococcal toxic shock syndrome in pediatrics. Presentation of 3
      cases].
AB  - Three cases of children admitted to the Pediatric Intensive Medicine Unit in the
      months of February to March 2004 with the diagnosis of streptococcal toxic shock
      syndrome are presented. Two were under 2 years of age and the initial symptoms
      suggested viriasis. They evolved towards septic shock with early multiorganic
      failure and then death due to massive hemoptysis, ventricular fibrillation due to
      hyperkaliemia. Streptococcus pyogenes with serotypes M1T1 was isolated in all the
      cases and the patients had the clinical criteria of streptococcal toxic shock
      syndrome. Their course was unfavorable in spite of the resuscitation steps, early
      antibiotic treatment and artificial support of the different organic failures. We
      stress the rareness of the cases, early age, its appearance in a short period of
      time, its sudden onset and the null response to treatment initiated.

PMID- 17433189
TI  - [Boutonneuse fever with severe neurological involvement].

PMID- 17433190
TI  - [Cost of intensive medicine services].

PMID- 17433191
TI  - [Torsades-de-pointes-type ventricular tachycardia in a patient with digitalis
      intoxication under chronic treatment with quinine sulfate].

PMID- 17433193
TI  - [Images in intensive medicine].

PMID- 17433195
TI  - [Measurement of drinking water contaminants and water use activities during
      pregnancy in a cohort study in Spain].
AB  - OBJECTIVES: Exposure to chlorination by-products during pregnancy has been
      associated with reproductive outcomes but the evidence remains inconclusive.
      Levels of trihalomethanes, the most prevalent chlorination by-products, are high
      in some areas of Spain. Within the framework of a follow-up study in pregnant
      women, we describe: 1) the personal habits of water use and consumption, and 2)
      trihalomethane levels in the drinking water of the study areas. METHODS: We
      performed a follow-up cohort study in pregnant women in Valencia (n = 800),
      Sabadell (n = 800), the Basque Country (n = 600), Asturias (n = 500), and Granada
      (n = 700). Interviews were conducted in the third trimester of pregnancy to
      obtain individual information on the sources and amounts of drinking water, and
      on the frequency of showering, bathing, and swimming pool attendance. Water
      samples were collected to analyze trihalomethane levels. RESULTS: The main source
      of drinking water was bottled water, both inside and outside the home (82% and
      94% of the women, respectively). Drinking water for cooking was mainly municipal
      (91%). Women preferred to take showers (98.2%) and did so, on average, 6.8
      times/week for 11.7 minutes. A total of 58.5% of the women went to swimming pools
      during pregnancy, on average 9.4 times/month to outdoor swimming pools in the
      summer and 3.1 times/month the rest of the year for 32.6 and 21.7 minutes,
      respectively. Average trihalomethane levels ranged from 4 microg/l in the
      province of Granada to 117 microg/l in Sabadell. CONCLUSION: These preliminary
      results suggest that the main routes of trihalomethane exposure during pregnancy
      are dermal absorption and inhalation. Ingestion is a minor exposure route.

PMID- 17433196
TI  - [Practical considerations on detection of publication bias].
AB  - The present review aims to answer 3 questions: does publication bias need to be
      assessed in meta-analyses?; what procedures, not requiring complex statistical
      approaches, can be applied to detect it?; and should other factors be taken into
      account when interpreting the procedures? The first question is easy to answer.
      Publication bias is a potential threat to the validity of the conclusions of meta
      analyses. Therefore, both the MOOSE and QUOROM statements include publication
      bias in their guidelines; nevertheless, many meta-analyses do not use these
      statements (e.g., meta-analyses conducted by the Cochrane Collaboration), perhaps
      because they use a comprehensive search strategy. There are many methods to
      assess publication bias. The most frequently used are funnel plots or <<Christmas
      trees>>, <<trim and fill>> (which allow the effects of bias to be estimated), and
      methods based upon regression on plots, such as Egger's method and funnel plot
      regression. An advantage of these methods is that they can only be applied using
      published data. However, agreement between these methods in detecting bias is
      often poor. Therefore, application of more than one method to detect publication
      bias is recommended. To correctly interpret the results, the number of pooled
      studies should be more than 10 and the existence of heterogeneity in the pooled
      estimate must be taken into account.

PMID- 17433197
TI  - [Measurement of chronic conditions in a single person as a mortality predictor].
AB  - The presence of multiple chronic diseases in a single individual has become an
      increasing public health problem for two reasons: population aging and the
      growing prevalence of chronic conditions in the elderly. This article aims to
      review the various measures of chronic conditions used in different morbidity
      studies and to provide an example of their application. We present definitions
      and characteristics of distinct morbidity measures, as well as their advantages
      and disadvantages, and provide an example of their calculation using real data.
      The presence of multiple chronic diseases in a single individual can be measured
      in multiple ways. Thus, morbidity can be expressed as multi-morbidity, co
      morbidity, or as a co-morbidity index. Researchers have to select the best option
      according to the research objectives, study design, information resources, and
      the main outcome variable selected.

PMID- 17433198
TI  - [Recommendations on ethical considerations in population screening programs for
      rare diseases].

PMID- 17433199
TI  - [Use of a retail sales tax on tobacco to fund drug therapy for smoking
      cessation].
AB  - OBJECTIVES: To analyze the revenue-generating potential of a new retail sales tax
      on tobacco and its effects on public health if the tax revenues were allocated to
      finance smoking cessation programs. METHODS: We provide an extensive review of
      the legislation on the authority of autonomous communities to order the levy and
      collection of special taxes and describe the new tobacco retail sales tax. We
      calculated collected tax revenues with a simulation model of indirect taxation 
      the SINDIEF (Simulador de Imposicion Indirecta del Instituto de Estudios
      Fiscales) model- and determined the potential number of smokers who would quit
      smoking. Epidemiological and clinical variables from existing pharmacological
      therapies were used to obtain the results. RESULTS: For the highest tax rate (20
      eurocents per pack), we found that 1,078,000 smokers yearly would give up
      smoking, suggesting that the new tax could be considered as a way to promote
      pharmacotherapy in smoking behavior. CONCLUSIONS: Fiscal corresponsability to
      finance smoking cessation programs could be based on a tobacco retailing sales
      tax, similar to that levied on hydrocarbons. Simulations for different tax rates
      show the huge potential of the tax to yield revenues, as the tax is levied yearly
      on 4.6 billion cigarette packs each year.

PMID- 17433200
TI  - Accuracy of cancer death certificates in Spain: a summary of available
      information.
AB  - OBJECTIVES: Differences in mortality rates within Europe might be partly due to
      the quality of mortality statistics. The present article summarizes the available
      data on the quality of cancer death certification in Spain. A short description
      of the temporal distribution of the proportion of deaths due to ill-defined
      tumors in Spain -an indirect indicator of the quality of cancer death
      certification- is also provided. METHODS: Relevant studies were identified from
      electronic databases (MEDLINE, EMBASE, IME and IBECS) and from manual searches of
      the references contained in the articles retrieved. Quality data on death
      certificates for all tumors and for each specific cancer location were
      summarized, and all main cancer sites were classified according to their pooled
      accuracy indicators. Trends for the percentage of deaths due to ill-defined
      tumors and conditions were studied for the period from 1980 to 2002. RESULTS: In
      Spain, deaths from cancer as a whole and leading cancer sites (lung, colon
      rectum, prostate, stomach, pancreas, female breast, uterus, brain, leukemia,
      lymphomas and myeloma) were well-certified. However, other frequent locations,
      such as the larynx, esophagus and liver were overcertified, while deaths from
      bladder, kidney and ovarian cancer were undercertified. The percentage of deaths
      due to ill-defined tumors and causes was regularly higher in females and
      decreased in both sexes during the study period. However, the recent introduction
      of the International Classification of Diseases (ICD)-10 has reversed this trend.
      CONCLUSIONS: Spanish death certificates can be considered as accurate and useful
      to estimate the burden of cancer, though certification of some frequent sites
      should be improved. The possible effect of the introduction of the ICD-10
      requires careful surveillance.

PMID- 17433202
TI  - [The challenge to public health of the Millenium Development Goals: an approach
      from political epidemiology].
AB  - The Millennium Development Goals, and within these the Millennium Targets,
      constitute a working plan that strives to achieve basic goals within the field of
      health, eradicate poverty, and ensure compliance with basic human rights. Its
      scope of action represents a historic breakthrough as a step toward a possible
      global social policy, in which cooperation between the different sectors is
      essential for its efficiency. Due to its multidisciplinary nature, public health,
      as well as political epidemiology, can be used to help increase scientific
      knowledge in the field of health with respect to the Millennium Development
      Goals. Despite the opportunity that this international agreement provides,
      insufficient in-depth study has been carried out on the potential -mainly
      political- difficulties that could arise during its implementation. Therefore, a
      conceptual and methodological change is required so that concern does not simply
      center on social determinants of health but instead takes into consideration the
      political reasons behind them. To reduce inequality, not only must injustice be
      classified but effective ways must also be found to encourage institutions with
      political power to take part in this initiative.

PMID- 17433201
TI  - [Guide to the principles and methods of health sentinel networks in Spain].
AB  - Health sentinel networks are being increasingly used in the study of health
      related problems. The present article aims to provide a methodological guide -
      designed by regional sentinel network managers and based on the results of a
      Delphi study - that can be used to set up and develop a health sentinel network.
      The main topics in the guide are the following: definition of a health sentinel
      network; network description: aims and structure; methods for the selection of
      sentinel participants; description of health processes suitable for study through
      this methodology: incidence, case definition, exclusion and inclusion criteria;
      description of the target population: the denominator for incidence rates
      estimates; quality indicators; periodicity of data collection; dissemination of
      the information: periodicity and methods, and incorporation of the participants
      in the decision-making process through multidisciplinary commissions. This guide
      aims to contribute to the development of sentinel networks in the autonomous
      communities by providing a common methodology, which could be highly useful when
      introducing new networks in Spain. Finally, we conclude that it is important to
      raise awareness of the concept of health sentinel networks, disseminate the
      information generated, and promote its use by public health administration.

PMID- 17433203
TI  - [Limits to the power of medicine to define disease and risk factor, and
      quarternary prevention].
AB  - Patient safety means to avoid unnecessary harm produces by health care
      activities. Quaternary prevention is a medical activity that try to avoid or
      decrease the health consequences of unnecessary or excesive health care.
      Physicians' definition of health, risk factor and disease justify many
      unnecessary medical interventions. It is critical to control an excesive medical
      technological actitude that allows excesive medical interventions. The medical
      power of definition of health and disease transform risk factor in a border which
      usually overlap with the disease field. We need research on quaternary
      prevention, and to develop activities of quaternary prevention which help in
      stopping the dissemination of health care (preventive, curative, diagnostic or
      therapeutic) of little value.

PMID- 17433204
TI  - [The organization of public health in the USA: a federal model].
AB  - The present article analyzes the structure of public health services in the USA.
      It aims to describe the perspective of 200 years of a federal organization of
      public health services, which could be useful in the current context in Spain.
      Information was obtained by interviews with key informants from the three levels
      of government (federal, state, and local) and with academics (many of whom had
      previous experience as public health officers). Special attention is paid to the
      organization, financing and activities of local and state health departments, as
      well as to the relationships between these departments. The implications for a
      country like Spain, which has evolved in a short period from a highly centralized
      system to a decentralized system based on 17 Autonomous Communities, is
      discussed.

PMID- 17433205
TI  - Lipid and lipoprotein concentrations at age 4. Association with neonatal and
      parental levels.
AB  - BACKGROUND AND OBJECTIVE: To study the influence of diet, anthropometrical
      measurements and neonatal and parental lipoprotein variables on lipoprotein
      concentrations at age 4. SUBJECTS AND METHOD: 18 neonates with normal serum
      lipoprotein values (group 1), 19 neonates with high total cholesterol (TC) levels
      (group 2) and 21 neonates with normal TC but altered levels in other lipids,
      apolipoproteins, lipoproteins or ratios (group 3) were selected for a follow-up
      study. Body weight, body mass index (BMI) and the suitability of diet at age 4
      for coronary heart disease prevention were evaluated. Multivariable stepwise
      linear regression analyses were performed for each lipid or lipoprotein parameter
      at age 4 considering group at birth, diet, neonatal and parental BMI, lipid or
      lipoprotein parameters. RESULTS: A large percentage of 4 year-olds had high low
      density lipoproteins-cholesterol (LDLc) and low high density lipoproteins
      cholesterol (HDLc) and followed an unsuitable diet. Prevalence of altered
      lipoprotein variables, except for TC/HDLc, was similar in the 3 groups.
      Correlations of birth versus 4 year levels were significant (p = 0.021-0.0001)
      for all parameters except triglycerides, TC and LDLc. However, all tracking
      correlations were not significant in group 3. In the multiple regression study,
      parental and neonatal parameters were retained as explicative variables in many
      of the models but diet was not retained in any of them. Maternal concentrations
      were always more explicative than paternal or neonatal ones. Models for TC/HDLc
      and LDLc/HDLc were the most explicative (both, R2 > 0.578; p < 0.0001).
      CONCLUSIONS: Lipoprotein variables at age 4 were more closely associated with
      progenitors' and neonatal lipoprotein values than BMI or diet.

PMID- 17433206
TI  - [Incidence of cardiovascular disease and validity of equations of coronary risk
      in diabetic patients with metabolic syndrome].
AB  - BACKGROUND AND OBJECTIVE: We aimed to analyze the contribution of the metabolic
      syndrome (MetS) and the glycemic control on the incidence of cardiovascular
      disease in type 2 diabetic patients. Our goal was also to validate to 10 years
      the coronary risk functions charts that use the original Framingham equation
      (Framingham-Wilson) and the calibrated one for the Spanish population (Framingham
      REGICOR) in diabetic patients with MetS. PATIENTS AND METHOD: We included a total
      of 206 diabetic patients from a primary care center (63.6% with MetS), with no
      history of cardiovascular disease, in whom the coronary risk could be calculated
      prior to 1 January 1995. All were followed up during 10 years. RESULTS: The
      incidence of stroke, coronary and global events was similar in diabetic patients
      with and without MetS (15.3% vs 14.7%, 9.2% vs 9.3% and 20.6% vs 21.3%,
      respectively). The presence of glycosylated hemoglobin > or = 7% increased the
      risk of global cardiovascular events (relative risk [RR], 2.13; 95% confidence
      interval [CI], 1.10-4.09) and stroke (RR, 3.4; 95% CI, 1.17-9.84). The considered
      coronary risk in Framingham-Wilson and REGICOR equations was higher in the
      patients with MetS (29.6% and 12.4% vs 23.4% and 9.4%, respectively; p < 0,01),
      but the validity criteria of these equations in the diabetic population are very
      discreet. CONCLUSIONS: A value of glycosylated hemoglobin > or = 7% increases the
      risk of cardiovascular events in diabetic patients whereas the incidence of this
      events was similar in patients with and without MetS. The utility of the
      Framingham-Wilson and REGICOR equations is reduced in the diabetic population.

PMID- 17433207
TI  - [Estimating utility values for health status using the Spanish version of the SF
      36. Validity of the SF-6D index vs EQ-5D].
AB  - BACKGROUND AND OBJECTIVE: A new utility index derived of the SF-36, the SF-6D,
      was recently developed and has been compared with other utility measures. The
      objective was to validate this index in the Spanish version of SF-36 with respect
      to the EQ-5D. METHOD: 1,843 complete measures of the SF-36 and the EQ-5D from
      1,283 patients who received a solid organ transplant were collected. SF-6D values
      were calculated using the model proposed by its creator and without tariff values
      (not weighted). EQ-5D values were calculated using Spanish visual analog scale
      tariff (VAS-t), the time-trade off tariff (TTO-t) and also without tariff values
      (not weighted). Spearman correlation coefficients were calculated between SF-6D
      and EQ-5D values. RESULTS: Mean value (standard deviation) of SF-6D was 0.67
      (0.15), of VAS-t, 0.69 (0.24) and of TTO-t, 0.70 (0.32). SF-6D values had
      moderate correlation with VAS-t (r = 0.734) and TTO-t (r = 0.731) (both p <
      0.001). The not weighted SF-6D had a high correlation with the weighted version
      (r = 0.969, p < 0.001), and moderate with the VAS-t (r = 0.754), TTO-t (r =
      0.750) and no weighted EQ-5D (r = 0.784) (p < 0.001). CONCLUSIONS: The SF-6D
      index derived from the Spanish version of SF-36 seem to be a valid utility index
      to be used with the SF-36 databases from studies made in Spain.

PMID- 17433208
TI  - [From children's cholesterol to cholesterol's children].

PMID- 17433209
TI  - [Response in primary healthcare and good professional reputation: something more
      than good clinical practice].

PMID- 17433210
TI  - [Randon [corrected] and lung cancer. Implications for health workers, citizens
      and public administrators].

PMID- 17433211
TI  - [Influence of lifestyle in patients with gastroesophageal reflux disease].
AB  - The prevalence of the symptoms of reflux (hearthburn and acid regurgitation) and
      of gastro-esophageal reflux disease is high. Numerous lifestyle modifications
      have been advocated in the prognosis of reflux. Obesity, the decubitus, eating
      rapidly, tobacco, alcohol and exercise provoke symptoms of the reflux (hearthburn
      and acid regurgitation). The proportion of fat in the food and stress aren't
      factors associated with reflux. Some works point at the chocolate, at the acid
      juices, at the carbonated beverages and at the onions as factors that unleash
      symptoms of reflux. Nevertheless larger prospective controlled trials are
      warranted. Gum-chewing after eating, keep standing up and to go to bed 4 h after
      dinner improves the symptoms of the reflux and the gastro-esophageal reflux
      disease.

PMID- 17433212
TI  - [Stichreaktion, centenial punctirreaction].

PMID- 17433213
TI  - [Validation of cardiovascular risk tables: are we more or less confused?].

PMID- 17433214
TI  - [Treament with statins after a stroke or a transient ischemic attack. Coffee for
      all?].

PMID- 17433215
TI  - [Lung collapse therapy with lucite balls].

PMID- 17433217
TI  - [Plea pro domo vaccino].

PMID- 17433218
TI  - [Lymphocyte migration in stromal cell networks].

PMID- 17433219
TI  - [Angiogenesis under Delta-Notch couple control].

PMID- 17433220
TI  - [The central circadian clock and peripheral clocks: decentralization and
      hierarchical control].

PMID- 17433221
TI  - [Suppression of non-specific transcription by the proteasome in embryonic stem
      cells].

PMID- 17433222
TI  - [New Bcl10 regulation mechanisms: a step in the comprehension of what has
      occurred in MALT lymphomas?].

PMID- 17433223
TI  - [TP53 and RB tumor suppressor pathways collaborate in retinoblastoma genesis].

PMID- 17433224
TI  - [What's new on ES cells?].

PMID- 17433226
TI  - [Mucosal immunity and vaccine development].
AB  - Mucosae constitute the major entry for most microbial pathogens but also
      innocuous antigens derived from ingested food, airborne matter or commensal
      bacteria. A large and highly specialized innate and adaptative mucosal immune
      system protects the mucosal surfaces and the body interior from potential
      injuries from the environment. The mucosal immune system has developed a variety
      of immune mechanisms to discriminate between non-pathogenic and pathogenic
      invaders. It is able to maintain tolerance against the plethora of environmental
      antigens and to induce potent protective immunity to avoid mucosal colonisation
      and organism invasion by dangerous microbial pathogens. Mucosal immunisation with
      appropriate antigens and immunostimulatory molecules may induce potent protective
      immunity against harmful pathogens. Alternatively, mucosally-induced tolerance
      against auto-antigens or allergens may be generated by mucosal administration of
      these antigens alone or with immunomodulators potentiating regulatory responses.
      Here, we review the properties of the mucosal immune system and briefly discuss
      the advances in the development of mucosal vaccines for protection against
      infections and for the treatment of inflammatory disorders such as autoimmune
      diseases or type I allergies.

PMID- 17433227
TI  - [New routes of administration: epidermal, transcutaneous mucosal ways of
      vaccination].
AB  - A successful vaccine triggers the interaction of various cells of the immune
      system as does a regular immune response. It is thus necessary to introduce the
      vaccine antigens into an anatomic site where they will contact immune cells. The
      route of administration is thus critical for the outcome of vaccination.
      Intramuscular or subcutaneous injections are the most popular. Antigens injected
      intramuscularly can form persistent precipitates that are dissolved and re
      absorbed relatively slowly. If injecting antigens is a quick, easy and
      reproducible way to vaccination, it requires trained personnel. Alternatives
      exist, through non-invasive formulations which allow administration by the
      patient or a third party with no particular expertise. The skin, especially its
      epidermal layer, is an accessible and competent immune environment and an
      attractive target for vaccine delivery, through transcutaneous delivery or
      immunostimulant patches. Mucosal immunization is another strategy: its major
      rationale is that organisms invade the body via mucosal surfaces. Therefore,
      local protection at mucosal surface as well as systemic defense is beneficial.
      Various formulations of mucosal vaccines have been developed, such as the Sabin
      oral polio vaccine (OPV), rotavirus vaccines, cold-adapted influenza vaccines or
      vaccine against typhoid fever. Thus we are entering in an era where mucosal and
      transcutaneous immunisation will play an important role in disease management.
      However, it has not been so easy to obtain regulatory approval for mucosal or
      transcutaneous formulations and needle-based vaccines continue to dominate the
      market.

PMID- 17433228
TI  - [New technologies for vaccine development].
AB  - Despite important success of preventive vaccination in eradication of smallpox
      and in reduction in incidence of poliomyelitis and measles, infectious diseases
      remain the principal cause of mortality in the world. Technologies used in the
      development of vaccines used so far, mostly based on empirical approaches, are
      limited and insufficient to fight diseases like malaria, acquired
      immunodeficiency syndrome (AIDS) or adult tuberculosis. Until recently,
      technologies for making vaccines were based on live attenuated microorganisms,
      whole killed microorganisms and subunit vaccines such as purified toxoids.
      Fortunately, the recent advances in the understanding of host-pathogen
      interaction as well as our increasing knowledge of how immune responses are
      triggered and regulated have opened almost unlimited possibilities of developing
      new immunization strategies based on recombinant microorganisms or recombinant
      polypeptides or bacterial or viral vectors, synthetic peptides, natural or
      synthetic polysaccharides or plasmid DNA. Thus, considering the expending number
      of technologies available for making vaccines, it becomes possible for the first
      time in the history of vaccinology to design vaccines based on a rational
      approach and leading to increased efficacy and safety.

PMID- 17433229
TI  - [Benefit-risk assessment of vaccination strategies].
AB  - This article summarises the various stages of the risk/benefit assessment of
      vaccination strategies. Establishing the awaited effectiveness of a vaccination
      strategy supposes to have an epidemiologic description of the disease to be
      prevented. The effectiveness of the vaccine strategy will be thus expressed in
      numbers of cases, hospitalizations or deaths avoided. The effectiveness can be
      direct, expressed as the reduction of the incidence of the infectious disease in
      the vaccinated subjects compared to unvaccinated subjects. It can also be
      indirect, the unvaccinated persons being protected by the suspension in
      circulation of the pathogenic agent, consecutive to the implementation of the
      vaccination campaign. The risks of vaccination related to the adverse effects
      detected during the clinical trials preceding marketing are well quantified, but
      other risks can occur after marketing: e.g., serious and unexpected adverse
      effects detected by vaccinovigilance systems, or risk of increase in the age of
      cases if the vaccination coverage is insufficient. The medico-economic evaluation
      forms a part of the risks/benefit assessment, by positioning the vaccine strategy
      comparatively with other interventions for health. Epidemiologic and
      vaccinovigilance informations must be updated very regularly, which underlines
      the need for having an operational and reliable real time monitoring system to
      accompany the vaccination strategies. Lastly, in the context of uncertainty which
      often accompanies the risks/benefit assessments, it is important that an adapted
      communication towards the public and the doctors is planned.

PMID- 17433230
TI  - [Impact of vaccination on the infectious diseases epidemiology: example of
      pertussis].
AB  - Several vaccines are now routinely used since fifty years in different developed
      countries. Their principal impact has been to decrease morbidity and mortality of
      the infectious diseases they are targeting. One disease, smallpox, is eradicated,
      poliomyelitis will be soon, diphteria is controlled in several countries but
      pertussis is still endemic although an efficacious vaccine was used. Why?
      Pertussis is an example of an infection for which the immunity of the population
      has changed after the introduction of generalized vaccination with killed whole
      cell pertussis vaccines, from a natural immunity due to infection to different
      types of vaccine-induced immunity. These different types of immunity have changed
      the protection against infection, disease and transmission. The impact of the
      generalized vaccination in a human population has been an important change in the
      epidemiology of the disease. In fact, a child-to-child transmission observed
      before the introduction of vaccination is now replaced by an adolescent-adult to
      infant transmission. The major consequence is an increase in the mortality and
      morbidity in non vaccinated infants mostly contaminated by their parents.
      Researches undertaken on the agent of the disease, the bacterium, Bordetella
      pertussis, conducted to the development of subunits vaccines, efficacious and
      better tolerated by infants than whole-cell vaccines. Many developed countries
      decided to change vaccines but also to add vaccine boosters for adolescents and
      adults in order to stop the transmission of the disease to infants. However, even
      after 15 years of studies in many countries, pertussis is still underestimated in
      adults and generalized adult vaccination remains difficult. The new goal now is
      to give information to medical students and health care workers in general in
      order to increase adolescent and adult's vaccination coverage.

PMID- 17433231
TI  - [Basis for vaccine recommendations].
AB  - Once a new vaccine has been granted its licensing, a public health expertise is
      needed in order to support the decision regarding its possible inclusion within
      the national immunisation schedule. This analysis, based on an assessment of the
      benefits/risks balance and costs/effectiveness ratio, is a multidisciplinary
      exercise. Largely based on epidemiological and immunological expertises, it also
      requires bio-mathematical and economical inputs, if the long term consequences of
      the vaccination are to be taken into account. Indeed, the main drivers of the
      decision are the burden of the disease, the characteristics of the vaccine in
      term of effectiveness and safety, the cost of the vaccination, the feasibility of
      the adjunction of the vaccine in the schedule, the social demand for this
      vaccination and the positive or negative indirect effects of a large vaccination
      on the epidemiology of the disease, in addition to the direct protective effect
      for vaccinated individuals. New vaccines are generally characterised by a more
      limited epidemiological impact than older vaccines, in a context of growing
      requirements from our society regarding drugs, and especially vaccines, safety.
      Both the real and perceived benefits/risks balances for the more recent vaccines
      appear questionable. The possibility of detrimental epidemiological consequences
      of either insufficient vaccination coverage or serotype (or serogroup)
      replacement is another factor that makes the decision regarding vaccination
      strategies increasingly complex.

PMID- 17433232
TI  - [Global immunization policies and recommendations: objectives and process].
AB  - The World Health Organization (WHO) has a dual mandate of providing global
      policies, standards and norms as well as support for member countries in applying
      such policies and standards to national programmes with the aim to improve
      health. The vaccine world is changing and with it the demands and expectations of
      the global and national policy makers, donors, and other interested parties.
      Changes pertain to : new vaccines and technologies developments, vaccine safety
      issues, regulation and approval of vaccines, and increased funding flowing
      through new financing mechanisms. This places a special responsibility on WHO to
      respond effectively. WHO has recently reviewed and optimized its policy making
      structure for vaccines and immunization and adjusted it to the new Global
      Immunization Vision and Strategy, which broadens the scope of immunization
      efforts to all age groups and vaccines with emphasis on integration of
      immunization delivery with other health interventions. This includes an extended
      consultation process to promptly generate evidence base recommendations, ensuring
      transparency of the decision making process and added communication efforts. This
      article presents the objectives and impact of the process set to develop global
      immunization policies, norms, standards and recommendations. The key advisory
      committees landscape contributing to this process is described. This includes the
      Strategic Advisory Group of Experts, the Global Advisory Committee on Vaccine
      Safety and the Expert Committee on Biological Standardization. The elaboration of
      WHO vaccine position papers is also described.

PMID- 17433233
TI  - [Vaccines and exposed occupations].
AB  - The use of safe and efficacious vaccines in occupational settings to protect
      workers from diseases to which they may be exposed is obvious and has been
      included in the employment law. Healthcare workers are particular exposed.
      Immunization has two purposes : protect the worker from contracting a disease,
      but also prevent him from disseminating the disease to weakened patients. It is
      important not only to take into account existing recommendations for
      immunization, but also to envisage their extension to teachers and staff of
      nurseries and primary schools. Routine vaccination against whooping cough,
      varicella, measles and hepatitis A is particularly warranted in these categories.
      Recommendations should also extend to medical students who are too often poorly
      protected and insufficiently warned against potential occupational exposure to
      pathogens and dissemination to their patients.

PMID- 17433234
TI  - [Preventing papillomavirus infectious and herpes zoster: new vaccines].
AB  - Two new vaccines have been recently licensed : a quadrivalent vaccine against
      Human papillomavirus infections (HPV) 6, 11, 16 and 18, recommended to children
      from 9 years old and to young adults under the age of 26 years, and a vaccine
      against herpes zoster for adults from 60 years old onwards. A bivalent vaccine
      against HPV 16 and 18 will be shortly available. HPV vaccines are composed of the
      L1 structural proteins of 2 or 4 HPV genotypes, produced by genetic engineering
      and self-assembled. These inert vaccines are devoid of genetic materials and
      mimic the viral particle (virus-like particle, VLP). They allow, as suggested by
      the 4.5 to 5 years follow-up, to prevent HPV infections and the onset of pre
      cancerous lesions associated with genotypes contained within the vaccine. They
      represent a major overhang in the vaccinology field, and, as anti-hepatitis B
      vaccine, will probably be effective in cancer prevention. Their use must be
      associated with the continued detection of cervix cancer by smears and also with
      the prevention of other sexually transmitted diseases. The herpes zoster vaccine
      is a living attenuated vaccine produced from the OKA/Merck strain already used in
      the vaccine against varicella. Its safety is good among persons 50 years old and
      over and its efficiency on lowering herpes zoster incidence, on the burden of
      illness and on post-herpetic neuralgia has been demonstrated in persons over 60
      years old.

PMID- 17433235
TI  - [Vaccines, the modern state and societies].
AB  - The vaccines are regarded as a major contribution to the retreat of the
      infectious diseases at the XX th century: they allowed a demographic rise without
      precedent in the world, even if there is still an important shift between the
      countries. A watershed is in the years 1950, with the beginning of the production
      of vaccines on cellular cultures and the first clinical trials concerning
      millions of people. It marks the beginning of the diversification of the vaccines
      and their production with an industrial scale, which makes it possible to
      consider new strategies and give precise contents to the dreams of eradication
      which had been expressed as of the Pasteurian time.

PMID- 17433236
TI  - [Medicen Paris Region: A world-class ''competitiveness cluster'' in the Paris
      region incorporating a neuroscience ''subcluster''].
AB  - The French public-private partnerships known as "competitive clusters" [poles de
      competitivite (PdC)] are intended to be novel and ambitious engines of regional
      growth, employment and biomedical innovation. Partly funded by government and
      local councils, they aim to capitalize on regional expertise by bringing together
      basic scientists, clinicians, innovative entrepreneurs and local decision-makers
      around specific themes that have become too costly and complex for any of these
      actors to tackle alone. Clusters provide the critical mass required both to
      underpin innovation potential and to authenticate regional claims to
      international competitiveness. Medicen is a biomedicine and therapeutics cluster
      comprising 120 partners from four broad "colleges" in the greater Paris region:
      major industry, small and medium-sized businesses, teaching hospitals/State
      research bodies, and local councils. Chief among its cooperative R&D projects is
      the neuroscience subcluster, in which "TransAl" the neurodegenerative disease
      project, counts Sanofi-Aventis, Servier and the French Atomic Energy Commission
      [Commissariat a l'Energie Atomique (CEA)] as key partners. One main aim is to
      develop an experimental model in rhesus monkeys in which a putative cause of
      Alzheimer's disease, intracerebral accumulation of b-amyloid peptide, is
      generated by impairing the peptide's clearance. The other aim, in which the
      nuclear medicine expertise of the CEA will be crucial, is to identify,
      characterize and validate markers for magnetic resonance and positron emission
      tomography imaging, and to source biomarkers from cerebrospinal fluid proteomics.
      A human biological resource centre (DNA and tissue banks) project dedicated to
      neurological and psychiatric disease should be up and running in 2007. Only
      through fundamental restructuring of resources on such a large cooperative scale
      are solutions likely to be found to the major problems of modern medicine,
      bringing healthcare and regional socioeconomic benefits in its wake.

PMID- 17433237
TI  - A same gene for altruism and selfishness in primates.
AB  - The goal of the International Alt/Self Project (IASP) is to determine the
      molecular basis of societal altruistic and selfish behaviour in primate
      societies. In order to solve this difficult problem, an International Consortium
      comprising genomists and psycho-biologists from the G-8 countries has been
      created. In a first step it was decided to concentrate on extreme opposite
      phenotypes manifesting in Homo sapiens sapiens: the hyper-altruism syndrome (HAS)
      and the hyper-selfishness syndrome (HSS). Conventional association methods, using
      the most powerful tools provided by the SNR, and the HumMap projects, resulted in
      the preliminary mapping of the ''altruist'' locus, and the ''selfish'' locus,
      both in the pseudo-autosomal region of the short arm of chromosome X.
      Transcriptional studies using 1000K chips showed that an unannotated sequence was
      overexpressed in HAS and underexpressed in HSS individuals. This mirror pattern
      of expression suggested that the two deviant states might be allelic. This
      hypothesis was substantiated by genome studies using GGH-array. Ultimately
      different mutations in expressed genomic sequences showed a striking genotype
      phenotype correlation: gain-of-function (GOF) mutations were invariably found in
      the HAS group, whereas loss-of-function (LOF) mutations were invariably found in
      the HSS group. These results demonstrate that a same and unique novel gene,
      coined DARWIN, is involved in the two opposite deviant phenotypes, suggesting
      that the morbid locus is a GTL (quantitative trait locus). Preliminary
      comparative data obtained in non-human primates showed that the DARWIN gene is
      highly conserved. Like humans, chimpanzees (Pan troglodytes) have a single
      expressed gene copy located in a stable genomic domain, whereas the highly
      benevolent bonobo primate (Pan paniscus) has several expressed gene copies,
      located in a copy number variable region (CNVR), a situation that buffers
      phenotypic manifestation of LOF mutations.

PMID- 17433238
TI  - [Empathy vs self-interest: two opposite phenotypes produced by a same QTL].

PMID- 17433239
TI  - Managing the risk of comparing estimated breeding values across flocks or herds
      through connectedness: a review and application.
AB  - Comparing predicted breeding values (BV) among animals in different management
      units (e.g. flocks, herds) is challenging if units have different genetic means.
      Unbiased estimates of differences in BV may be obtained by assigning base animals
      to genetic groups according to their unit of origin, but units must be connected
      to estimate group effects. If many small groups exist, error of BV prediction may
      be increased. Alternatively, genetic groups can be excluded from the statistical
      model, which may bias BV predictions. If adequate genetic connections exist among
      units, bias is reduced. Several measures of connectedness have been proposed, but
      their relationships to potential bias in BV predictions are not well defined.
      This study compares alternative strategies to connect small units and assesses
      the ability of different connectedness statistics to quantify potential bias in
      BV prediction. Connections established using common sires across units were most
      effective in reducing bias. The coefficient of determination of the mean
      difference in predicted BV was a perfect indicator of potential bias remaining
      when comparing individuals in separate units. However, this measure is difficult
      to calculate; correlated measures such as prediction errors of differences in
      unit means and correlations among prediction errors are suggested as practical
      alternatives.

PMID- 17433240
TI  - A periodic analysis of longitudinal binary responses: a case study of clinical
      mastitis in Norwegian Red cows.
AB  - A Bayesian procedure for analyzing longitudinal binary responses using a periodic
      cosine function was developed. It was assumed that, after adjustment for
      "seasonal" effects, the oscillation of the underlying latent variables for
      longitudinal binary responses was a stationary series. Based on this assumption,
      a single dimension sinusoidal analysis of longitudinal binary responses using the
      Gibbs sampling and Metropolis algorithms was implemented in a study of clinical
      mastitis records of Norwegian Red cows taken over five lactations.

PMID- 17433241
TI  - Empirical evaluation of selective DNA pooling to map QTL in dairy cattle using a
      half-sib design by comparison to individual genotyping and interval mapping.
AB  - This study represents the first attempt at an empirical evaluation of the DNA
      pooling methodology by comparing it to individual genotyping and interval mapping
      to detect QTL in a dairy half-sib design. The findings indicated that the use of
      peak heights from the pool electropherograms without correction for stutter
      (shadow) product and preferential amplification performed as well as corrected
      estimates of frequencies. However, errors were found to decrease the power of the
      experiment at every stage of the pooling and analysis. The main sources of errors
      include technical errors from DNA quantification, pool construction, inconsistent
      differential amplification, and from the prevalence of sire alleles in the dams.
      Additionally, interval mapping using individual genotyping gains information from
      phenotypic differences between individuals in the same pool and from neighbouring
      markers, which is lost in a DNA pooling design. These errors cause some
      differences between the markers detected as significant by pooling and those
      found significant by interval mapping based on individual selective genotyping.
      Therefore, it is recommended that pooled genotyping only be used as part of an
      initial screen with significant results to be confirmed by individual genotyping.
      Strategies for improving the efficiency of the DNA pooling design are also
      presented.

PMID- 17433242
TI  - Fine mapping of multiple QTL using combined linkage and linkage disequilibrium
      mapping--a comparison of single QTL and multi QTL methods.
AB  - Two previously described QTL mapping methods, which combine linkage analysis (LA)
      and linkage disequilibrium analysis (LD), were compared for their ability to
      detect and map multiple QTL. The methods were tested on five different simulated
      data sets in which the exact QTL positions were known. Every simulated data set
      contained two QTL, but the distances between these QTL were varied from 15 to 150
      cM. The results show that the single QTL mapping method (LDLA) gave good results
      as long as the distance between the QTL was large (>90 cM). When the distance
      between the QTL was reduced, the single QTL method had problems positioning the
      two QTL and tended to position only one QTL, i.e. a "ghost" QTL, in between the
      two real QTL positions. The multi QTL mapping method (MP-LDLA) gave good results
      for all evaluated distances between the QTL. For the large distances between the
      QTL (>90 cM) the single QTL method more often positioned the QTL in the correct
      marker bracket, but considering the broader likelihood peaks of the single point
      method it could be argued that the multi QTL method was more precise. Since the
      distances were reduced the multi QTL method was clearly more accurate than the
      single QTL method. The two methods combine well, and together provide a good tool
      to position single or multiple QTL in practical situations, where the number of
      QTL and their positions are unknown.

PMID- 17433243
TI  - Within-family marker-assisted selection for aquaculture species.
AB  - A within-family marker-assisted selection scheme was designed for typical
      aquaculture breeding schemes, where most traits are recorded on sibs of the
      candidates. Here, sibs of candidates were tested for the trait and genotyped to
      establish genetic marker effects on the trait. BLUP breeding values were
      calculated, including information of the markers (MAS) or not (NONMAS). These
      breeding values were identical for all family members in the NONMAS schemes, but
      differed between family members in the MAS schemes, making within-family
      selection possible. MAS had up to twice the total genetic gain of the
      corresponding NONMAS scheme. MAS was somewhat less effective when heritability
      increased from 0.06 to 0.12 or when the frequency of the positive allele was
      <0.5. The relative efficiency of MAS was higher for schemes with more candidates,
      because of larger fullsib family sizes. MAS was also more efficient when
      male:female mating ratio changed from 1:1 to 1:5 or when the QTL explained more
      of the total genetic variation. Four instead of two markers linked to the QTL
      increased genetic gain somewhat. There was no significant difference in polygenic
      genetic gain between MAS and NONMAS for most schemes. The rates of inbreeding
      were lower for MAS than NON-MAS schemes, because fewer full-sibs were selected by
      MAS.

PMID- 17433244
TI  - Genetic diversity and population structure inferred from the partially duplicated
      genome of domesticated carp, Cyprinus carpio L.
AB  - Genetic relationships among eight populations of domesticated carp (Cyprinus
      carpio L.), a species with a partially duplicated genome, were studied using 12
      microsatellites and 505 AFLP bands. The populations included three aquacultured
      carp strains and five ornamental carp (koi) variants. Grass carp
      (Ctenopharyngodon idella) was used as an outgroup. AFLP-based gene diversity
      varied from 5% (grass carp) to 32% (koi) and reflected the reasonably well
      understood histories and breeding practices of the populations. A large fraction
      of the molecular variance was due to differences between aquacultured and
      ornamental carps. Further analyses based on microsatellite data, including
      cluster analysis and neighbor-joining trees, supported the genetic
      distinctiveness of aquacultured and ornamental carps, despite the recent
      divergence of the two groups. In contrast to what was observed for AFLP-based
      diversity, the frequency of heterozygotes based on microsatellites was comparable
      among all populations. This discrepancy can potentially be explained by
      duplication of some loci in Cyprinus carpio L., and a model that shows how
      duplication can increase heterozygosity estimates for microsatellites but not for
      AFLP loci is discussed. Our analyses in carp can help in understanding the
      consequences of genotyping duplicated loci and in interpreting discrepancies
      between dominant and co-dominant markers in species with recent genome
      duplication.

PMID- 17433245
TI  - Extensive intragenic recombination and patterns of linkage disequilibrium at the
      CSN3 locus in European rabbit.
AB  - Kappa-casein (CSN3) plays an important role in stabilising the Ca-sensitive
      caseins in the micelle. The European rabbit (Oryctolagus cuniculus) CSN3 has
      previously been shown to possess two alleles (A and B), which differ deeply in
      their intronic regions (indels of 100 and 1550 nucleotides in introns 1 and 4,
      respectively). Furthermore, a correlation between several reproductive
      performance traits and the different alleles was described. However, all these
      data were exclusively collected in rabbit domestic breeds, preventing a deeper
      understanding of the extensive polymorphism observed in the CSN3 gene.
      Additionally, the techniques available for the typing of both indel polymorphisms
      were until now not suitable for large-scale studies. In this report, we describe
      a simple, PCR-based typing method to distinguish rabbit CSN3 alleles. We analyse
      both ancient wild rabbit populations from the Iberian Peninsula and France, and
      the more recently derived English wild rabbits and domestic stocks. A new allele
      (C) showing another major indel (250 bp) in intron 1 was found, but exclusively
      detected in Iberian wild rabbits. In addition, our survey revealed the occurrence
      of new haplotypes in wild populations, suggesting that intragenic recombination
      is important in creating genetic diversity at this locus. This easy and low cost
      single-step PCR-based method results in an improvement over previous described
      techniques, can be easily set up in a routine molecular laboratory and would
      probably be a valuable tool in the management of rabbit domestic breeds.

PMID- 17433246
TI  - A simple and sensitive assay for ascorbate using a plate reader.
AB  - We have developed a rapid, inexpensive, and reliable assay for the determination
      of ascorbate using a plate reader. In this assay, ascorbic acid is oxidized to
      dehydroascorbic acid using Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy)
      and then reacted with o-phenylenediamine to form the condensation product, 3
      (dihydroxyethyl)furo[3,4-b]quinoxaline-1-one. The rate of appearance of this
      product is monitored over time using fluorescence. With this method, it is
      possible to analyze 96 wells in less than 10min. This permits the analysis of 20
      samples with a full set of standards and blanks, all in triplicate. The assay is
      robust for a variety of samples, including orange juice, swine plasma, dog
      plasma, and cultured cells. To demonstrate the usefulness of the assay for the
      rapid determination of experimental parameters, we investigated the uptake of
      ascorbate and two different ascorbate derivatives in U937 cells. We found similar
      plateau levels of intracellular ascorbate at 24h for ascorbate and ascorbate
      phosphate. However, the intracellular accumulation of ascorbate via the phosphate
      ester had an initial rate that was three to five times slower than that via the
      palmitate ester. Only lower concentrations of the palmitate ester could be
      examined because the ethanol needed as solvent decreased cell viability; it
      behaved similarly to the other two compounds at lower concentrations. To come to
      these conclusions, only nine plates needed to be analyzed to provide us with the
      end result after only 7h of analysis. This clearly demonstrates the strength of
      the plate reader assay, which allows the analysis of large-sample sets in a
      fraction of the time required for the methods that are most commonly used today.
      The assay is quick, is very economical, and provides results with uncertainties
      on the order of only 5%.

PMID- 17433247
TI  - Site-directed biotinylation of antibodies for controlled immobilization on solid
      surfaces.
AB  - Site-directed biotinylation of antibodies at the hinge region was developed to
      immobilize antibodies in an oriented manner via biotin-streptavidin linkage. When
      intact antibody was biotinylated with maleimide-activated biotin after reduction,
      the reaction preferentially occurred at the sulfhydryl groups between the C(H1)
      and the C(L) domains and, provided that the reagent concentration exceeded a
      certain level, at those between the C(H2) and the C(H2) domains at the hinge.
      Based on this result, we devised an approach in which free maleimide was added to
      compete with the activated biotin for the preferential sites between the C(H1)
      and the C(L) domains. Since the smaller molecular size of free maleimide made it
      more accessible for the reaction than biotin, maleimide bound to the groups
      between the C(H1) and the C(L) domains first and thus conceded the groups between
      the C(H2) and the C(H2) domains to biotin under optimal conditions. In an
      alternative approach, selective biotinylation at the hinge was also achieved by
      reacting activated biotin with F(ab')(2) fragment prepared by enzymatic cleavage.
      This result indicated that, when free of Fc, the hinge structure, which contains
      the functional groups, of the fragment was open, allowing easy access to the
      biotin derivative from the aqueous medium. Both site-directed biotinylation
      preparations were tested as capture antibodies in sandwich-type immunoassays and
      compared to whole antibody randomly biotinylated at amino groups on the molecule.
      Preparations of both the intact antibody and the F(ab')(2) showed consistently
      enhanced detection capabilities that were 2.6 and 20 times that of the control,
      respectively.

PMID- 17433248
TI  - Occlusal tooth wear in female F344/N rats with aging.
AB  - OBJECTIVES: This study was conducted to ascertain whether laboratory rats are an
      adequate animal model for aging oral cavity research, especially on occlusal
      tooth wear (OTW), which progresses with aging and causes abnormal occlusions.
      Mastication has been reported to relate to cognition in the elderly. Thus, it is
      important to care for the oral cavity, especially in the frail elderly, for the
      maintenance of all-round quality of life. Adequate and appropriate animal models
      are essential for basic and clinical research on the oral cavity. METHODS: Dried
      maxilla and mandible specimens from 98 young, aging or aged female F344/N rats
      were used. RESULTS: The levels of OTW of all molars were monitored with aging.
      The molar tooth began to wear at 1-month old (M) and progressed rapidly till 12M.
      Subsequently, OTW progressed slowly till 30M, and then rapidly again after 35M.
      CONCLUSIONS: This study showed that progress of OTW is well correlated with the
      entire life span of the rat, and suggested that the rat aged over 12M would be an
      adequate animal model for research on OTW in middle-aged and elderly people.

PMID- 17433249
TI  - Density and diameter of dentinal tubules in etched and non-etched bovine dentine
      examined by scanning electron microscopy.
AB  - Bovine teeth have been widely used in studies focusing adhesion to dentine over
      the last years. However, little is known about main structural aspects of bovine
      dentine, especially regarding density and diameter of its tubules. Thirty bovine
      incisors were randomly divided into two groups. In group I, teeth were cross
      sectioned at three depths: outer, middle and inner. The dentinal surfaces were
      etched with 35% phosphoric acid for 90s. In group II, the teeth were fractured at
      the same three depths. All the specimens were processed and examined in a Jeol
      6100 SEM. Fifteen micrographs from each depth were obtained for the two groups at
      a magnification of 2500x. To determine the diameter of the dentinal tubules, the
      LEICA Q500 MC software was used. All the results were statistically processed in
      the EXCEL software. The dentinal tubules were wider at the outer regions (GI:
      5.21+/-0.64microm; GII: 2.30+/-0.09microm) than that at the inner regions (GI:
      2.71+/-0.72microm; GII: 1.77+/-0.06microm). Tubular density was higher at the
      inner regions (50310+/-11178tubules/mm(2)) than that at the outer regions
      (18772+/-2951tubules/mm(2)). In addition, the peritubular dentine was wider at
      the outer depth than at the inner one. Our results showed that bovine dentine
      possesses some structural aspects different from those previously reported for
      human dentine, mainly related to the diameter of dentinal tubules and to the
      thickness of peritubular dentine at the several depths.

PMID- 17433250
TI  - The redox chemistry of the Alzheimer's disease amyloid beta peptide.
AB  - There is a growing body of evidence to support a role for oxidative stress in
      Alzheimer's disease (AD), with increased levels of lipid peroxidation, DNA and
      protein oxidation products (HNE, 8-HO-guanidine and protein carbonyls
      respectively) in AD brains. The brain is a highly oxidative organ consuming 20%
      of the body's oxygen despite accounting for only 2% of the total body weight.
      With normal ageing the brain accumulates metals ions such iron (Fe), zinc (Zn)
      and copper (Cu). Consequently the brain is abundant in antioxidants to control
      and prevent the detrimental formation of reactive oxygen species (ROS) generated
      via Fenton chemistry involving redox active metal ion reduction and activation of
      molecular oxygen. In AD there is an over accumulation of the Amyloid beta peptide
      (Abeta), this is the result of either an elevated generation from amyloid
      precursor protein (APP) or inefficient clearance of Abeta from the brain. Abeta
      can efficiently generate reactive oxygen species in the presence of the
      transition metals copper and iron in vitro. Under oxidative conditions Abeta will
      form stable dityrosine cross-linked dimers which are generated from free radical
      attack on the tyrosine residue at position 10. There are elevated levels of urea
      and SDS resistant stable linked Abeta oligomers as well as dityrosine cross
      linked peptides and proteins in AD brain. Since soluble Abeta levels correlate
      best with the degree of degeneration [C.A. McLean, R.A. Cherny, F.W. Fraser, S.J.
      Fuller, M.J. Smith, K. Beyreuther, A.I. Bush, C.L. Masters, Soluble pool of Abeta
      amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease,
      Ann. Neurol. 46 (1999) 860-866] we suggest that the toxic Abeta species
      corresponds to a soluble dityrosine cross-linked oligomer. Current therapeutic
      strategies using metal chelators such as clioquinol and desferrioxamine have had
      some success in altering the progression of AD symptoms. Similarly, natural
      antioxidants curcumin and ginkgo extract have modest but positive effects in
      slowing AD development. Therefore, drugs that target the oxidative pathways in AD
      could have genuine therapeutic efficacy.

PMID- 17433251
TI  - Disgust sensitivity and psychopathological symptoms in non-clinical children.
AB  - There is clear evidence in the adult literature that disgust sensitivity is
      implicated in various psychopathological syndromes. The current study examined
      the link between disgust sensitivity and psychopathological symptoms in youths.
      In a sample of non-clinical children aged 9-13 years, disgust sensitivity was
      assessed by two self-report questionnaires (i.e., the Disgust Scale and the
      Disgust Sensitivity Questionnaire) and a behavioural test. Furthermore, children
      completed scales for measuring the personality trait of neuroticism and various
      types of psychopathological symptoms. Results showed that disgust measures had
      sufficient to good convergent validity. Further, significant positive
      correlations were found between disgust sensitivity and symptoms of specific
      phobias (i.e., spider phobia, blood-injection phobia, small-animal phobia),
      social phobia, agoraphobia, obsessive-compulsive disorder (OCD), and eating
      problems, and these links were not attenuated when controlling for neuroticism.
      The possible role of disgust sensitivity in the aetiology of child
      psychopathology is discussed.

PMID- 17433252
TI  - Why social anxiety persists: an experimental investigation of the role of safety
      behaviours as a maintaining factor.
AB  - Study one used a semi-structured interview to assess the use of safety behaviours
      in high and low socially anxious participants. As predicted from cognitive
      models, the high social anxiety group reported using a greater number of safety
      behaviours, more frequently, in a greater number of situations. Both the high and
      low social anxiety groups perceived their safety behaviours to be helpful. Study
      two involved experimentally manipulating the use of safety behaviours and self
      focus and demonstrated the use of safety behaviours and self-focused attention to
      be unhelpful in a number of ways. Results support the role of safety behaviours
      and self-focused attention in the cognitive model of social phobia, and the value
      of dropping safety behaviours and reducing self-focus as therapeutic strategies
      in social phobia.

PMID- 17433253
TI  - Nobiletin enhances differentiation and lipolysis of 3T3-L1 adipocytes.
AB  - Nobiletin is a polymethoxylated flavone found in certain citrus fruits. Here we
      demonstrate that nobiletin enhance differentiation of 3T3-L1 preadipocytes.
      Nobiletin dose-dependently increased accumulation of lipid droplets in
      adipocytes. Quantitative RT-PCR analyses indicated that nobiletin increased the
      expression of genes critical for acquisition of the adipocyte phenotype. Some of
      them were known peroxisome proliferator activated receptor gamma (PPARgamma)
      targets and PPARgamma itself, however, nobiletin did not exhibit PPARgamma ligand
      activity. We observed the expression of CCAAT/enhancer binding protein beta
      (C/EBPbeta), a transcription factor for PPARgamma, was increased by nobiletin.
      The activation of cAMP-responsive element binding protein (CREB) and
      extracellular signal-regulated kinase (ERK), which play important roles in
      C/EBPbeta expression were also potentiated by nobiletin. Furthermore, nobiletin
      stimulated lipolysis in differentiated adipocytes, which is known to be
      stimulated by cAMP pathway. These results suggested that nobiletin enhanced both
      differentiation and lipolysis of adipocyte through activation of signaling
      cascades mediated by cAMP/CREB.

PMID- 17433254
TI  - Placenta-derived multipotent stem cells induced to differentiate into insulin
      positive cells.
AB  - In the present study, we successfully isolated PDMSCs from human placental
      tissues. The RT-PCR results show that PDMSCs preserved the genetic
      characteristics of the primitive embryonic stage--Oct-4 and Nanog. By using serum
      free medium supplemented essential growth factors and induction medium culture
      for 4 weeks, a monolayer of spindle-like PDMSCs gradually formed 3D spheroid
      bodies (SB-PDMSCs). By using real-time RT-PCR, early mRNA expressions of Pdx1, as
      well as the Sox17 and Foxa2 genes, were observed to be significantly activated in
      SB-PDMSCs, followed by the expression of mature pancreas-related genes (insulin,
      glucagon, and somatostatin). The high insulin content of SB-PDMSCs was further
      confirmed by ELISA assay, and the glucose dependency was demonstrated by the
      corresponding insulin secretion level. In a transplantation study of
      streptozotocin-pretreated nude mice, the restoration of normoglycemia in the SB
      PDMSC treated group was further observed. In conclusion, these results indicate
      that PDMSCs are an excellent source for the induced differentiation of well
      functioning insulin-positive cells. The potential of these insulin producing
      cells derived from PDMSCs was also demonstrated functionally by the demonstration
      of secreted insulin in vitro and effective control of blood glucose levels in
      vivo.

PMID- 17433255
TI  - Identification of the auto-inhibitory domains of Aurora-A kinase.
AB  - Aurora-A is a centrosome-localized serine/threonine kinase that is overexpressed
      in multiple human cancers. Here, we report an intramolecular inhibitory
      regulation in Aurora-A between its N-terminal regulatory domain (aa 1-128, Nt)
      and the C-terminal catalytic domain (aa 129-403, Cd). Removal of Nt results in a
      significant increase in kinase activity. Nt inhibited the activity of the single
      C-terminal kinase domain, but had little effect on the activity of the full
      length of Aurora-A. PP1 is not involved in this regulation, instead, Nt interacts
      Cd directly in vitro and in vivo. The non-Aurora box (aa 64-128) in the N
      terminal negatively regulated the kinase activity of the C-terminal kinase domain
      by intramolecular interaction with aa 240-300 within the C-terminal.

PMID- 17433256
TI  - Prolactin upregulates its receptors and inhibits lipolysis and leptin release in
      male rat adipose tissue.
AB  - Prolactin (PRL) is recognized as a metabolic regulator during lactation, but
      little information exists on its actions in male adipose tissue. We examined
      whether PRL affects the expression of its receptors (PRLR), lipolysis, and
      adipokine secretion in male rats. Both long and short PRLR isoforms were induced
      40-50-fold during differentiation of epididymal preadipocytes, with a 10-fold
      higher expression of the long isoform. PRL upregulated both isoforms before and
      after differentiation. PRL suppressed lipolysis in epididymal explants and mature
      adipocytes in a dose- and time-dependent manner, which was reversed by a Jak2
      inhibitor. PRL also inhibited leptin, but not adiponectin, release. We conclude
      that PRL inhibits lipolysis and leptin release by acting directly on adipocytes
      via interaction with either of its receptors and activation of a Jak2-dependent
      signaling pathway(s). This is the first demonstration of substantial effects of
      PRL on male adipocytes.

PMID- 17433257
TI  - Identification and characterization of the human SOX6 promoter.
AB  - The present study attempted to identify and characterize the embryonic promoter
      of Sox6, a determinant regulator of chondrogenic differentiation. A common
      transcription start region for human and mouse Sox6 was initially identified,
      which contained a highly conserved sequence, A-box. Tandem repeats of A-box had a
      strong transcriptional activity both at the basal level and in response to Sox9.
      Cells carrying the 4xA-box-DsRed2 reporter fluoresced only upon chondrogenic
      differentiation. The 46-bp core enhancer region (CES6) was then identified in the
      3' half of A-box, within which a C/EBP-binding motif was identified.
      Overexpressed C/EBPbeta activated the Sox6 promoter, and mutant 4xCES6 constructs
      lacking the C/EBP motif lost their basal activity. CES6 and nuclear extracts
      formed a specific complex, which was supershifted by anti-C/EBPbeta antibody, and
      in vitro translated C/EBPbeta specifically bound to CES6. Thus, we successfully
      identified the Sox6 promoter and its core enhancer and characterized the
      interactions with regulatory transcription factors.

PMID- 17433258
TI  - Combined cupric- and cuprous-binding peptides are effective in preventing IL-8
      release from endothelial cells and redox reactions.
AB  - Copper mobilization and subsequent redox reactions have been implicated in the
      pathogenesis of numerous inflammation-based diseases. Reduction of the cupric ion
      (Cu(2+)) to the cuprous ion (Cu(+)) is necessary for the production of copper
      induced reactive oxygen species (ROS). Peptides, designed to bind both Cu(2+) and
      Cu(+) and have the ability to prevent copper redox reactions, were studied. The
      peptides DAHGMTCANC and DAHKGMTCANC were effective at preventing the formation of
      thiobarbituric acid-reactive species (TBARS) in a copper/ascorbate solution at a
      1:1 peptide/Cu ratio. This was observed in the reducing potential of the
      copper/ascorbate solutions containing these peptides at a 1:1 ratio based on
      oxidation-reduction potential (ORP) measurements. The peptide DAHGMTCARC was
      effective at a 2:1 ratio, but not at a 1:1 ratio in which an increase in the
      oxidation potential was observed. This suggests that a positively charged amino
      acid such as arginine (R) in the Cu(+)-binding motif interferes with metal
      chelation. All peptides tested were effective at preventing IL-8 release from
      phorbol 12-myristate 13-acetate (PMA)/copper-stimulated human umbilical vein
      endothelial cells (HUVEC). The use of Cu(+)/Cu(2+)-binding peptides might be
      beneficial in the treatment of ROS-related diseases associated with copper.

PMID- 17433259
TI  - Role of hypoxia-inducible factor-alpha in hepatitis-B-virus X protein-mediated
      MDR1 activation.
AB  - The transition from chemotherapy-responsive cancer cells to chemotherapy
      resistant cancer cells is mainly accompanied by the increased expression of multi
      drug resistance 1 (MDR1). We found that hepatitis-B-virus X protein (HBx)
      increases the transcriptional activity and protein level of MDR1 in a hepatoma
      cell line, H4IIE. In addition, HBx overexpression made H4IIE cells more resistant
      to verapamil-uptake. HBx stabilized hypoxia-inducible factor-1alpha (HIF-1alpha)
      and induced the nuclear translocation of C/EBPbeta. Reporter gene analyses showed
      that HBx increased the reporter activity in the cells transfected with the
      reporter containing MDR1 gene promoter. Moreover, the luciferase reporter gene
      activity was significantly inhibited by HIF-1alpha siRNA but not by
      overexpression of C/EBP dominant negative mutant. These results imply that HBx
      increases the MDR1 transporter activity through the transcriptional activation of
      the MDR1 gene with HIF-1alpha activation, and suggest HIF-1alpha for the
      therapeutic target of HBV-mediated chemoresistance.

PMID- 17433260
TI  - Prediction of protein structural class for the twilight zone sequences.
AB  - Structural class characterizes the overall folding type of a protein or its
      domain. This paper develops an accurate method for in silico prediction of
      structural classes from low homology (twilight zone) protein sequences. The
      proposed LLSC-PRED method applies linear logistic regression classifier and a
      custom-designed, feature-based sequence representation to provide predictions.
      The main advantages of the LLSC-PRED are the comprehensive representation that
      includes 58 features describing composition and physicochemical properties of the
      sequences and transparency of the prediction model. The representation also
      includes predicted secondary structure content, thus for the first time exploring
      synergy between these two related predictions. Based on tests performed with a
      large set of 1673 twilight zone domains, the LLSC-PRED's prediction accuracy,
      which equals over 62%, is shown to be better than accuracy of over a dozen
      recently published competing in silico methods and similar to accuracy of other,
      non-transparent classifiers that use the proposed representation.

PMID- 17433261
TI  - Bone morphogenetic protein-7 and interferon-alpha synergistically suppress
      hepatitis C virus replicon.
AB  - Various cytokines contribute to control hepatitis C virus (HCV) viral
      replication. HCV subgenomic replicon systems have been developed, and cell-cycle
      dependent replication has been reported. But the molecules involved in this
      processes is not totally elucidated. The aim of this study is to investigate the
      involvement of the bone morphogenetic protein (BMP)-7, a member of TGF-beta
      superfamily, to the in vitro HCV replication. BMP-7 dose-dependently suppressed
      the replication and protein expression from the HCV replicon in Huh7/Rep-Feo
      cells and was associated with cell-cycle arrest at the G1 phase. These results
      were consistent with the effect of TGF-beta in a previous study. Combination of
      BMP-7 and interferon-alpha showed a synergic decrease of HCV replication, and was
      more effective compared to the treatment with interferon-alpha alone. This
      synergistic effect was also present in HCV-JFH1 virus cell culture. While BMP-7
      alone did not stimulate expression of the interferon-stimulated genes (ISGs), it
      augmented interferon-induced expression of the ISGs independently of the
      interferon-induced Jak/STAT pathway. Taken together, BMP-7 may constitute a novel
      molecule to suppress HCV replication.

PMID- 17433262
TI  - Roles of CYP3A4 and CYP2C19 in methyl hydroxylated and N-oxidized metabolite
      formation from voriconazole, a new anti-fungal agent, in human liver microsomes.
AB  - Involvement of cytochrome P450 (P450 or CYP) 2C19, 2C9, and 3A4 in N-oxidation of
      voriconazole, a new triazole antifungal agent, has been demonstrated using human
      liver microsomes. To confirm the precise roles of P450 isoforms in voriconazole
      clearance in individuals, we investigated the oxidative metabolism of
      voriconazole catalyzed by recombinant P450s as well as human liver microsomes
      genotyped for the CYP2C19 gene. Among recombinant P450 isoforms using Escherichia
      coli expression systems, CYP2C19 and CYP3A4 had voriconazole N-oxidation
      activities, but not CYP2C9. Apparent K(m) and V(max) values of CYP2C19 and CYP3A4
      for voriconazole N-oxidation were 14+/-6 microM and 0.22+/-0.02 nmol/min/nmol
      CYP2C19 and 16+/-10 microM and 0.05+/-0.01 nmol/min/nmol CYP3A4, respectively
      (mean+/-S.E.). CYP3A4 produced a new methyl hydroxylated metabolite from
      voriconazole, detected by LC/UV and LC/MS/MS and confirmed by 1H and 13C NMR
      analyses, with K(m) and V(max) values of 11+/-3 microM and 0.10+/-0.01
      nmol/min/nmol CYP3A4. The voriconazole 4-hydroxylation to N-oxidation metabolic
      ratios in liver microsomes from the wild-type CYP2C19*1/*1 individuals (0.07)
      were lower than those observed in other genotypes (0.20-0.27) at a substrate
      concentration of 25 microM based on the reported clinical plasma level. These
      results suggest that the CYP2C19 genotype, but not CYP2C9 genotype, would be
      evaluated as a key factor in the pharmacokinetics of voriconazole and that 4
      hydroxyvoriconazole formation may become an important pathway for voriconazole
      metabolism in individuals with poor CYP2C19 catalytic function.

PMID- 17433263
TI  - Human glutathione transferases catalyzing the bioactivation of anticancer
      thiopurine prodrugs.
AB  - cis-6-(2-Acetylvinylthio)purine (cAVTP) and trans-6-(2-acetylvinylthio)guanine
      (tAVTG) are thiopurine prodrugs provisionally inactivated by an alpha,beta
      unsaturated substituent on the sulfur of the parental thiopurines 6
      mercaptopurine (6-MP) and 6-thioguanine (6-TG). The active thiopurines are
      liberated intracellularly by glutathione (GSH) in reactions catalyzed by
      glutathione transferases (GSTs) (EC 2.5.1.18). Catalytic activities of 13 human
      GSTs representing seven distinct classes of soluble GSTs have been determined.
      The bioactivation of cAVTP and tAVTG occurs via a transient addition of GSH to
      the activated double bond of the S-substituent of the prodrug, followed by
      elimination of the thiopurine. The first of these consecutive reactions is rate
      limiting for thiopurine release, but GST-activation of this first addition is
      shifting the rate limitation to the subsequent elimination. Highly active GSTs
      reveal the transient intermediate, which is detectable by UV spectroscopy and
      HPLC analysis. LC/MS analysis of the reaction products demonstrates that the
      primary GSH conjugate, 4-glutathionylbuten-2-one, can react with a second GSH
      molecule to form the 4-(bis-glutathionyl)butan-2-one. GST M1-1 and GST A4-4 were
      the most efficient enzymes with tAVTG, and GST M1-1 and GST M2-2 had highest
      activity with cAVTP. The highly efficient GST M1-1 is polymorphic and is absent
      in approximately half of the human population. GST P1-1, which is overexpressed
      in many cancer cells, had no detectable activity with cAVTP and only minor
      activity with tAVTG. Other GST-activated prodrugs have targeted GST P1-1
      expressing cancer cells. Tumors expressing high levels of GST M1-1 or GST A4-4
      can be predicted to be particularly vulnerable to chemotherapy with cAVTP or
      tAVTG.

PMID- 17433264
TI  - Regulatory mechanisms underlying GKR2 levels in U937 cells: evidence for GRK3
      involvement.
AB  - G protein-coupled receptors represent the most diverse group of proteins involved
      in transmembrane signalling, that participate in the regulation of a wide range
      of physicochemical messengers through the interaction with heterotrimeric G
      proteins. In addition, GPCRs stimulation also triggers a negative feedback
      mechanism, known as desensitization that prevents the potentially harmful effects
      caused by persistent receptor stimulation. In this adaptative response, G protein
      coupled receptor kinases (GRKs) play a key role and alterations in their function
      are related to diverse pathophysiological situations. Based on the scarce
      knowledge about the regulation of GRK2 by other kinases of the same family, the
      aim of the present work was to investigate the regulation of GRK2 levels in
      systems where other GRKs are diminished by antisense technique. Present findings
      show that in U937 cells GRK2 levels are regulated by GRK3 and not by GRK6 through
      a mechanism involving InsP upregulation. This work reports a novel GRK3-mediated
      GRK2 regulatory mechanism and further suggests that GRK2 may also act as a
      compensatory kinase tending to counterbalance the reduction in GRK3 levels. This
      study provides the first evidence for the existence of GRKs cross-regulation.

PMID- 17433265
TI  - Poly(ADP-ribose) polymerase inhibition by cilostazol is implicated in the
      neuroprotective effect against focal cerebral ischemic infarct in rat.
AB  - This study shows that cilostazol displayed a potent inhibition of PARP with
      IC(50) of 883+/-41 nM in the enzyme assay, and also significantly reversed
      H(2)O(2)-evoked elevated PARP activity and reduced NAD(+) levels in the PC12
      cells with improvement of cell viability. In in vivo study, inhibition of PARP
      activity by cilostazol prevented cerebral ischemic injury induced by 2-h middle
      cerebral artery occlusion (MCAO) and 24-h reperfusion. The ischemic infarct was
      significantly reduced in the rats that received cilostazol (30 mg/kg, twice
      orally) with improvement of neurological function. Moreover, cilostazol treatment
      significantly decreased the number of terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick end labeling (TUNEL)- and poly(ADP-ribose)-positive
      cells associated with apoptosis-inducing factor (AIF) translocation to the
      nucleus in the penumbral region. Further, cilostazol significantly reduced
      myeloperoxidase activity, a marker of neutrophil infiltration. In line with these
      findings, the OX-42- (a marker of microglia) and TNF-alpha-positive cells (a
      marker of proapoptotic protein) were markedly increased in the vehicle samples,
      both of which were significantly attenuated by treatment with cilostazol. Taken
      together, these results suggest that neuroprotective potentials of cilostazol
      against focal cerebral ischemic injury are, at least in part, ascribed to its
      anti-inflammatory effects and PARP inhibitory activity.

PMID- 17433266
TI  - Characterization of brainstem preproglucagon projections to the paraventricular
      and dorsomedial hypothalamic nuclei.
AB  - In the brain preproglucagon expression is limited to a cluster of neurons in the
      caudal part of the nucleus of the solitary tract (NTS) as well as a smaller
      number of neurons that extend laterally from the NTS through the dorsal reticular
      area into the A1 area. These neurons process preproglucagon to glucagon-like
      peptide-1 (GLP-1), GLP-2, oxyntomodulin and glicentin. The neurons project mainly
      to the hypothalamus, where especially two nuclei involved in appetite regulation-
      the paraventricular (PVN) and dorsomedial (DMH) hypothalamic nuclei--are heavily
      endowed with GLP-immunoreactive nerve fibres. To gain further insight into this
      neurocircuitry, we injected the retrograde tracers cholera toxin, subunit B (ChB)
      and Fluorogold (FG) into the PVN and the DMH, respectively. Of thirty-five
      injected rats, six had successful injections that predominantly restricted within
      the boundaries of the PVN and DMH. Hindbrain sections from these rats were triple
      labelled for ChB, FG and GLP-2. A total of 24+/-1% of the PVN-projecting NTS
      neurons contained GLP-2-ir whereas 67+/-4% of the DMH-projecting neurons were
      also stained for GLP-2, suggesting that the NTS-projections to the DMH arise
      mainly from preproglucagon neurons. Approximately 20% of backfilled cells in the
      NTS contained both retrograde tracers, therefore presumably representing neurons
      projecting to both the PVN and the DMH. The results of the present study
      demonstrate that the majority of the preproglucagon-expressing neurons in the NTS
      project in a target-specific manner to the hypothalamus. It is therefore possible
      that individual subgroups of GLP-containing neurons can mediate different
      physiological responses.

PMID- 17433267
TI  - Improgan-induced hypothermia: a role for cannabinoid receptors in improgan
      induced changes in nociceptive threshold and body temperature.
AB  - Improgan, a congener of the H(2) antagonist cimetidine, produces non-opioid
      antinociception which is blocked by the CB(1) antagonist rimonabant, implying a
      cannabinoid mechanism of action. Since cannabinoids produce hypothermia as well
      as antinociception in rodents, the present study investigated the pharmacological
      activity of improgan on core body temperature and nociceptive (tail flick)
      responses. Improgan (60, 100 and 140 microg, intraventricular [ivt]) elicited
      significant decreases in core temperature 3-30 min following injection with a
      maximal hypothermic effect of -1.3 degrees C. Pretreatment with rimonabant (50
      microg, ivt) produced a statistically significant but incomplete (29-42%)
      antagonism of improgan hypothermia. In control experiments, the CB(1) agonist CP
      55,940 (37.9 microg, ivt) induced significant decreases in core temperature (-1.8
      degrees C) 3-30 min following injection. However, unlike the case with improgan,
      pretreatment with rimonabant completely blocked CP-55,940 hypothermia.
      Furthermore, CP-55,940 and improgan elicited maximal antinociception over the
      same time course and dose ranges, and both effects were attenuated by rimonabant.
      These results show that, like cannabinoid agonists in the rat, improgan produces
      antinociception and hypothermia which is blocked by a CB(1) antagonist. Unlike
      cannabinoid agonists, however, improgan does not produce locomotor inhibition at
      antinociceptive doses. Additional experiments were performed to determine the
      effect of CC12, a recently discovered improgan antagonist which lacks affinity at
      CB(1) receptors. Pretreatment with CC12 (183 microg, ivt) produced complete
      inhibition of both the antinociception and the hypothermia produced by improgan,
      suggesting the possible role of an unknown improgan receptor in both of these
      effects.

PMID- 17433268
TI  - The functional difference between transient and sustained K+ currents on the
      action potentials in tetrodotoxin-resistant adult rat trigeminal ganglion
      neurons.
AB  - To determine whether there is a difference between a transient K(+) current
      (I(A)) and a sustained K(+) current (I(K)) regarding the neuronal function in
      small-diameter adult rat trigeminal ganglion (TG) neurons, which were insensitive
      to tetrodotoxin (TTX, 1 microM), we performed two different types of experiments.
      Primary cultures of dissociated TG neurons were prepared, and
      electrophysiological recordings were performed with the whole-cell configuration
      using the patch-clamp technique. In the voltage-clamp mode, two distinct K(+)
      current components, (I(A)) and (I(K)), were identified, and two different
      components (59.5% and 96.3%) of I(K) to the total K(+) current were observed at a
      +50 mV step-pulse. The IC(50) value for 4-aminoprydine (4-AP, 0.05-50 mM), which
      inhibited the I(A) by 50%, was 0.7 mM. That for tetraethylammonium (TEA, 0.02-20
      mM) to inhibit 50% of I(K) was 1.5 mM. In the current-clamp mode, we used 0.5 mM
      4-AP and 2 mM TEA at each concentration nearly equal to the IC(50) value.
      Irrespective of the absence or presence of TEA (2 mM), 0.5 mM 4-AP application
      increased the number of action potentials due to the decreased duration of the
      depolarization phase (DDP). TEA in the presence and absence of 4-AP prolonged the
      duration of action potentials as well as the duration of repolarization phase
      (DRP). These results suggested that I(A) and I(K) had independent effects
      regulating the intrinsic firing properties of the action potential number and
      timing, respectively, in adult rat TTX-R TG neurons.

PMID- 17433269
TI  - Oncosis, the possible cell death pathway in astrocytes after focal cerebral
      ischemia.
AB  - Swelling of astrocytes at early stage of cerebral ischemia has been reported,
      however, the fate and the cell death pathway of astrocytes are still unclear.
      Focal cerebral ischemia was induced in Sprague-Dawley rats by permanent occlusion
      of middle cerebral artery for 3 to 48 h. Haematoxylin and eosin (HE) staining,
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL),
      glial fibrillary acidic protein (GFAP), caspase-3 immunostaining, and double
      staining with TUNEL and GFAP were carried out on consecutive sections. The
      ultrastructure was revealed by electron microscopy. Using electron microscope,
      apoptotic neurons were confirmed with condensed chromatin and apoptotic bodies.
      In the core of the infarct, clumps of heterochromatin around the edge of nucleus,
      vacuolar degeneration of the nucleus and leakage of chromatin were demonstrated
      at 3, 6, and 12 h respectively in the swelling astrocytes, which accorded with
      the process of oncosis; in the peripheral zone of the infarct, reactive
      astrocytes with nuclear membranes preserved demonstrated increased cell size and
      number and coexisted with oncotic astrocytes. Scattered GFAP-positive cells and
      ubiquitous caspase-3-positive cells were found in the core after 12 h following
      cerebral ischemia, and no cells positive for double-staining with TUNEL and GFAP
      were found in the ischemic regions, indicating that most GFAP-positive astrocytes
      did not die by apoptosis. Findings from present study demonstrate that after
      cerebral ischemia, oncosis may be the possible cell death pathway of astrocytes
      in the ischemic region, and oncotic astrocytes coexist with reactive astrocytes
      in the peripheral zone.

PMID- 17433270
TI  - beta-Estradiol induces synaptogenesis in the hippocampus by enhancing brain
      derived neurotrophic factor release from dentate gyrus granule cells.
AB  - We investigated the effect of beta-estradiol (E2) on synaptogenesis in the
      hippocampus using organotypic hippocampal slice cultures and subregional
      hippocampal neuron cultures. E2 increased the expression of PSD95, a postsynaptic
      marker, specifically in stratum lucidum of Cornu Ammonis 3 (CA3SL) in cultured
      hippocampal slices. E2 also increased the spine density at the proximal site of
      CA3 apical dendrites in CA3SL and PSD95 was clustered on these spine heads. The
      effects of E2 on the expression of PSD95 and the spine density disappeared when
      the dentate gyrus (DG) had been excised at 1 day in vitro (DIV). FM1-43 analysis
      of subregional hippocampal neuron cultures which were comprised of Ammon's horn
      neurons, DG neurons, or a mixture of these neurons, revealed that E2 increased
      the number of presynaptic sites in the cultures that contained DG neurons. K252a,
      a potent inhibitor of the high affinity receptor of brain-derived neurotrophic
      factor (BDNF), and function-blocking antibody to BDNF (BDNFAB) completely
      inhibited the effects of E2 in hippocampal slice cultures and subregional neuron
      cultures, whereas ICI182,780 (ICI), a strong antagonist of nuclear estrogen
      receptors (nERs), did not. Expression of BDNF in DG neurons was markedly higher
      than that in Ammon's horn neurons and E2 did not affect these expression levels.
      E2 significantly increased the BDNF release from DG neurons. KT5720, a specific
      inhibitor of 3'-5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase
      A (PKA), and Rp-adenosine 3', 5'-cyclic monophosphorothioate triethylammonium
      salt (Rp-cAMP), a non-hydrolyzable diastereoisomer and a potent inhibitor of PKA,
      completely suppressed the E2-induced increase in BDNF release, whereas ICI and
      U0126, a potent inhibitor of MAP kinase kinase (MEK), did not. These results
      suggest that E2 induces synaptogenesis between mossy fibers and CA3 neurons by
      enhancing BDNF release from DG granule cells in a nER-independent and PKA
      dependent manner.

PMID- 17433271
TI  - Saccadic adaptation depends on object selection: evidence from between- and
      within-object saccadic eye movements.
AB  - The accuracy of saccadic eye movements is maintained by saccadic adaptation. Post
      saccadic visual feedback about the error between the target position and the
      saccade endpoint is crucial to the adaptive process. The present experiments
      examine the adaptation of saccades that select a new target object (between
      object saccades) and that of saccades that would not aim for a selected target
      but execute a fixed motor vector (within-object saccades). We show that the post
      saccadic visual error, induced by the intra-saccadic back step, leads to the
      adaptation of between-object saccades but not of within-object saccades.
      Furthermore, between-object saccade adaptation does not transfer to within-object
      saccades. These results suggest that saccadic adaptation depends on the selection
      of a precise target object.

PMID- 17433272
TI  - Increased vulnerability of hippocampal neurons with age in culture: temporal
      association with increases in NMDA receptor current, NR2A subunit expression and
      recruitment of L-type calcium channels.
AB  - Excessive glutamate (Glu) stimulation of the NMDA-R is a widely recognized
      trigger for Ca(2+)-mediated excitotoxicity. Primary neurons typically show a
      large increase in vulnerability to excitotoxicity with increasing days in vitro
      (DIV). This enhanced vulnerability has been associated with increased expression
      of the NR2B subunit or increased NMDA-R current, but the detailed age-courses of
      these variables in primary hippocampal neurons have not been compared in the same
      study. Further, it is not clear whether the NMDA-R is the only source of excess
      Ca(2+). Here, we used primary hippocampal neurons to examine the age dependence
      of the increase in excitotoxic vulnerability with changes in NMDA-R current, and
      subunit expression. We also tested whether L-type voltage-gated Ca(2+) channels
      (L-VGCCs) contribute to the enhanced vulnerability. The EC(50) for Glu toxicity
      decreased by approximately 10-fold between 8-9 and 14-15 DIV, changing little
      thereafter. Parallel experiments found that during the same period both amplitude
      and duration of NMDA-R current increased dramatically; this was associated with
      an increase in protein expression of the NR1 and NR2A subunits, but not of the
      NR2B subunit. Compared to MK-801, ifenprodil, a selective NR2B antagonist, was
      less effective in protecting older than younger neurons from Glu insult.
      Conversely, nimodipine, an L-VGCC antagonist, protected older but not younger
      neurons. Our results indicate that enhanced excitotoxic vulnerability with age in
      culture was associated with a substantial increase in NMDA-R current, concomitant
      increases in NR2A and NR1 but not NR2B subunit expression, and with apparent
      recruitment of L-VGCCs into the excitotoxic process.

PMID- 17433273
TI  - Dissecting the cytokine network.
AB  - Understanding the cytokine network is a very complex task. One way is the
      dissection of the network by the generation and analysis of mutant mice. As the
      technology advances more sophisticated approaches toward this goal become
      available and proof to disclose an even more complex picture of the cytokine
      network as we initially anticipated. This increase in complexity leads to
      fascinating challenges in the future.

PMID- 17433274
TI  - Systems biology of innate immunity.
AB  - Systems Biology has emerged as an exciting research approach in molecular biology
      and functional genomics that involves a systematic use of genomic, proteomic, and
      metabolomic technologies for the construction of network-based models of
      biological processes. These endeavors, collectively referred to as systems
      biology establish a paradigm by which to systematically interrogate, model, and
      iteratively refine our knowledge of the regulatory events within a cell. Here, we
      present a new systems approach, integrating DNA and transcript expression
      information, specifically designed to identify transcriptional networks governing
      the macrophage immune response to lipopolysaccharide (LPS). Using this approach,
      we are not only able to infer a global macrophage transcriptional network, but
      also time-specific sub-networks that are dynamically active across the LPS
      response. We believe that our system biological approach could be useful for
      identifying other complex networks mediating immunological responses.

PMID- 17433275
TI  - P2X(7) purinergic receptors and extracellular ATP mediate apoptosis of human
      monocytes/macrophages infected with Mycobacterium tuberculosis reducing the
      intracellular bacterial viability.
AB  - Mycobacterium tuberculosis (MTB) is a monocyte/macrophage (M/M) parasite, which
      has developed several mechanisms to survive and multiply intracellularly. On the
      other hand, infected cells are engaged in the effort to reduce mycobacterial
      viability. On this ground, we report that MTB infection predisposes M/M to a pro
      apoptotic ATP-based signalling, which is aimed at decreasing MTB replication. In
      fact, we show that mycobacterial infection leads to an increased expression of
      P2X(7) purinergic receptors, which is paralleled by intracellular accumulation
      and subsequent extracellular release of ATP by infected macrophages. Activation
      of this signal is conceived to induce apoptosis in MTB-infected cells, since
      blocking P2X(7) receptor by means of oxidized ATP (oATP) prevents MTB induced
      cell death. Finally, we show that an ATP stimulation of MTB-infected M/M, besides
      increasing cellular apoptosis, strongly enhances intracellular MTB killing, as
      evaluated through Colony Forming Unit assay, and such effect is subverted through
      oATP pulsing of infected cells. Taken together, our data indicate a role of
      P2X(7) purinergic receptors in MTB-induced M/M apoptosis, suggesting the
      existence of an autocrine/paracrine loop leading to apoptosis of infected M/M and
      the feasible protective role of ATP-triggered cell death in tuberculosis.

PMID- 17433276
TI  - Melanoma genomics reveals signatures of sensitivity to bio- and targeted
      therapies.
AB  - Most of the melanoma markers used today are melanocytic markers or pigmentation
      pathway-associated genes driven by the microphthalmia transcription factor, MITF,
      and include among others, tyrosinase, dopachrome tautomerase, DCT, melan-A and
      S100B. Genomic studies repeatedly revealed several novel melanoma marker genes
      including those of the transcription factor NOTCH2, WNT5A, proliferation
      associated genes TOPO2A and CDC2, membrane receptors FGFR and EphA3, adhesion
      molecules N-cadherin, beta3 integrin and syndecan-4, and the cell surface
      antigens CD59/protectin and MIA. Other genomic analyses tried to define the gene
      signature of the metastatic disease but failed to find a consistent one except
      the gold standard genes of beta3 integrin, syndecan-4 and WNT5a. Studies on the
      gene signatures of chemoresistance and cytokine sensitivity of melanoma clearly
      defined apoptosis-resistance as one of the key elements of the above biological
      properties, but the data are controversial, mostly because of the use of
      inappropriate model systems and the lack of confirmation on clinical samples.
      Accordingly, application of genomic technologies must be more "translational" to
      provide breakthrough in melanoma diagnosis and therapy.

PMID- 17433277
TI  - Evolution of robust and efficient system topologies.
AB  - Mutation/selection algorithms were applied to increase the efficiency and the
      robustness of sparse random networks. Selection for better efficiency leads to
      the well-known star topology, while selection for robustness only results in a
      relatively dense core and a small periphery. Concomitant selection for both
      efficiency and robustness leads to networks with intermittent center/periphery
      values. Networks evolving under multiple attack regimes develop distinct
      topologies with larger cores, and are characterized by parameter distributions
      different from those developing under single-attack regimes.

PMID- 17433278
TI  - Analysis of protein adduction kinetics by quantitative mass spectrometry:
      competing adduction reactions of glutathione-S-transferase P1-1 with
      electrophiles.
AB  - Defining the mechanisms and consequences of protein adduction is crucial to
      understanding the toxicity of reactive electrophiles. Application of tandem mass
      spectrometry and data analysis algorithms enables detection and mapping of
      chemical adducts at the level of amino acid sequence. Nevertheless, detection of
      adducts does not indicate relative reactivity of different sites. Here, we
      describe a method to measure the kinetics of competing adduction reactions at
      different sites on the same protein. Adducts are formed by electrophiles at Cys14
      and Cys47 on the metabolic enzyme glutathione-S-transferase P1-1 and modification
      is accompanied by a loss of enzymatic activity. Relative quantitation of protein
      adducts was done by tagging N-termini of peptide digests with isotopically
      labeled phenyl isocyanate and tracking the ratio of light-tagged peptide adducts
      to heavy-tagged reference samples in liquid chromatography-tandem mass
      spectrometry analyses using a multiple reaction monitoring method. This approach
      was used to measure rate constants for adduction at both positions with two
      different model electrophiles, N-iodoacetyl-N-biotinylhexylenediamine and 1
      biotinamido-4-(4'-[maleimidoethyl-cyclohexane]-carboxamido)butane. The results
      indicate that Cys47 was approximately two- to three-fold more reactive toward
      both electrophiles than was Cys14. This result was consistent with the relative
      reactivity of these electrophiles in a complex proteome system and with
      previously reported trends in reactivity of these sites. Kinetic analyses of
      protein modification reactions provide a means of evaluating the selectivity of
      reactive mediators of chemical toxicity.

PMID- 17433280
TI  - Striving for optimal relevance when answering questions.
AB  - When people are asked "Do you have the time?" they can answer in a variety of
      ways, such as "It is almost 3", "Yeah, it is quarter past two", or more precisely
      as in "It is now 1:43". We present the results of four experiments that examined
      people's real-life answers to questions about the time. Our hypothesis, following
      previous research findings, was that people strive to make their answers
      optimally relevant for the addressee, which in many cases allows people to give
      rounded, and not exact, time responses. Moreover, analyses of the non-numeral
      words, hesitations, and latencies of people's verbal responses to time questions
      reveal important insights into the dynamics of speaking to achieve optimal
      relevance. People include discourse markers, hesitation marks, like "uh" and
      "um", and pauses when answering time questions to maximize the cognitive effects
      (e.g., a rounded answer is adequate) listeners can infer while minimizing the
      cognitive effort required to infer these effects. This research provides new
      empirical evidence on how relevance considerations shape collaborative language
      use.

PMID- 17433279
TI  - Circulating small dense LDL, endothelial injuring factors and fibronectin in
      healthy postmenopausal women.
AB  - BACKGROUND: In postmenopausal women (PMW), an adverse lipoprotein pattern and
      high risk of coronary artery disease has been described. Studies of the
      mechanisms promoting the higher atherogenic risk observed in healthy PMW are
      relevant. We evaluated the interactions among several circulating factors
      involved in the endothelial injury and inflammation in relation to LDL
      characteristics, beyond LDL cholesterol. METHODS: Lipoprotein profile, including
      apolipoproteins A-I and B, small dense LDL, hepatic lipase, cholesterol transfer
      protein (CETP), LDL composition and oxidability were assessed in PMW (n=30) in
      comparison to premenopausal (PreMW, n=28). The following emerging factors were
      measured: homocysteine, phospholipase A2, ferritin, hs-CRP and fibronectin from
      extracellular vascular matrix. Insulin-resistance was evaluated by waist
      circumference, HOMA and TG/HDL cholesterol ratios. RESULTS: The risk index apo
      B/apo A-I was significantly increased in PMW (p<0.0001), PMW showed higher
      proportion of small dense LDL which correlated with the increase in hepatic
      lipase activity (p<0.005) and with insulin-resistance markers (p<0.05), but not
      with CETP. Phospholipase A2 (p<0.05), homocysteine (p<0.005), hs-CRP (p<0.005),
      fibronectin (p<0.05) and ferritin (p<0.0001) were increased in PMW. LDL
      oxidability positively correlated with waist (p<0.02), homocysteine (p<0.05),
      fibronectin (p<0.05), hs-CRP (p<0.04), phospholipase A2 (p<0.05), and small dense
      LDL (p<0.01). After adjusting by menopausal condition, age and waist, LDL
      oxidability remained associated with waist (beta: 0.35, p=0.047), homocysteine
      (beta: 0,36 p<0,038), fibronectin (beta: 0,41 p=0.05), and small dense LDL (beta:
      0.36, p=0.027). CONCLUSIONS: Evaluation of classic and non-traditional
      circulating risk factors in hypoestrogenism reflected endothelial and
      subendothelial inflammation and subclinical atherogenic processes.

PMID- 17433281
TI  - On prototypes as defaults (Comment on Connolly, Fodor, Gleitman and Gleitman,
      2007).

PMID- 17433282
TI  - The attentional cost of inattentional blindness.
AB  - When our attention is engaged in a visual task, we can be blind to events which
      would otherwise not be missed. In three experiments, 97 out of the 165 observers
      performing a visual attention task failed to notice an unexpected, irrelevant
      object moving across the display. Surprisingly, this object significantly lowered
      accuracy in the primary task when, and only when, it failed to reach awareness.
      We suggest that an unexpected stimulus causes a state of alert that would
      normally generate an attentional shift; if this response is prevented by an
      attention-consuming task, a portion of the attentional resources remains
      allocated to the object. Such a portion is large enough to disturb performance,
      but not so large that the object can be recognized as task-irrelevant and
      accordingly ignored. Our findings have one counterintuitive implication:
      irrelevant stimuli might hamper some types of performance only when perceived
      subliminally.

PMID- 17433283
TI  - Learning and modeling biosignatures from tissue images.
AB  - Ideally biosignatures can be detected at the early infection phase and used both
      for developing diagnostic patterns and for prognostic triage. Such biosignatures
      are important for vaccine validation and to provide risk stratification to a
      population such as for the identification of individuals who are exposed to
      biological or chemical agents and who are at high risk for developing an
      infection. The research goal is to detect broad based biosignature models and is
      initially focused on developing effective computer-augmented pathology tied to
      animal models developed at the University of New Mexico (UNM). Using lung tissue
      from infected and nai ve mice, feature extraction from images of the tissue under
      a specialized microscope, and Bayesian networks to analyze the data sets of
      features, we were able to differentiate normal from diseased samples and viral
      from bacterial samples in mid to late stages of infection. This effort has shown
      the potential effectiveness of computer-augmented pathology in this application.
      The extended research intends to couple analysis of serum, microarray analysis of
      organs, proteomic data and the pathology. The rational for the current invasive
      procedure on animal models is to facilitate the development of data analysis and
      machine learning techniques that can eventually be generalized to the task of
      discovering non-invasive and early stage biosignatures for human models.

PMID- 17433284
TI  - Issues concerning the large scale cryopreservation of peripheral blood
      mononuclear cells (PBMC) for immunotherapy trials.
AB  - Immunotherapy of cancer is being developed as an alternative or adjuvant to
      conventional therapies such as: surgery, chemotherapy and/or radiation treatment.
      Immunotherapy laboratories routinely process and prepare for injection large
      numbers of anti-tumor effector cells. The process of cryopreservation is critical
      to the success of immunotherapy. Standardized safe procedures are required. In
      the current report, we show the ability to cryopreserve peripheral blood
      mononuclear cells (PBMC) in Plasmalyte-A, a fluid replacement medium approved by
      the FDA. These studies show that this medium can be used in place of human serum
      in terms of cell recovery, cell surface phenotype and response to PHA. However, T
      cell cytokine release stimulated through the CD3 receptor was altered following
      the cryopreservation process. These results are important toward the improvement
      of cryopreservation techniques for their use in immunotherapy.

PMID- 17433285
TI  - Analysis of dishevelled localization and function in the early sea urchin embryo.
AB  - Dishevelled (Dsh) is a key signaling molecule in the canonical Wnt pathway.
      Although the mechanism by which Dsh transduces a Wnt signal remains elusive, the
      subcellular localization of Dsh may be critical for its function. In the early
      sea urchin embryo, Dsh is concentrated in punctate structures within the
      cytoplasm of vegetal blastomeres. In these cells, Dsh stabilizes beta-catenin and
      causes it to accumulate in nuclei, resulting in the activation of transcriptional
      gene regulatory networks that drive mesoderm and endoderm formation. Here, we
      present a systematic mutational analysis of Lytechinus variegatus Dsh (LvDsh)
      that identifies motifs required for its vegetal cortical localization (VCL). In
      addition to a previously identified lipid-binding motif near the N-terminus of
      Dsh (Weitzel, H.E., Illies, M.R., Byrum, C.A., Xu, R., Wikramanayake, A.H.,
      Ettensohn, C.A., 2004. Differential stability of beta-catenin along the animal
      vegetal axis of the sea urchin embryo mediated by dishevelled. Development 131,
      2947-56), we identify a short (21 amino acid) motif between the PDZ and DEP
      domains that is required for VCL. Phosphorylation of threonine residues in this
      region regulates both the targeting and stability of LvDsh. We also identify
      functional nuclear import and export signals within LvDsh. We provide additional
      evidence that LvDsh is active locally in the vegetal region of the embryo but is
      inactive in animal blastomeres and show that the inability of LvDsh to function
      in animal cells is not a consequence of impaired nuclear import. The DIX domain
      of LvDsh functions as a potent dominant negative when overexpressed (Weitzel,
      H.E., Illies, M.R., Byrum, C.A., Xu, R., Wikramanayake, A.H., Ettensohn, C.A.,
      2004. Differential stability of beta-catenin along the animal-vegetal axis of the
      sea urchin embryo mediated by dishevelled. Development 131, 2947-56). Here, we
      show that the dominant negative effect of DIX is dependent on a highly conserved,
      lipid-binding motif that includes residues K57 and E58. The dominant negative
      effect of DIX is not a consequence of blocking VCL or the nuclear import of
      LvDsh. We provide evidence that isolated DIX domains interact with full-length
      LvDsh in vivo. In addition, we show that the K57/E58 lipid-binding motif of DIX
      is essential for this interaction. We propose that binding of the isolated DIX
      domain to full-length Dsh may be facilitated by interactions with lipids, and
      that this interaction may inhibit signaling by a) preventing endogenous Dsh from
      interacting with Axin, or b) blocking the ability of Dsh to recruit other
      proteins, such as GBP/Frat1, to the beta-catenin degradation complex.

PMID- 17433288
TI  - Hau-Pax3/7A is an early marker of leech mesoderm involved in segmental
      morphogenesis, nephridial development, and body cavity formation.
AB  - Two genes of the Pax III subfamily, Hau-Pax3/7A and -Pax3/7B, were identified
      from the leech Helobdella, and the expression and function of Hau-Pax3/7A in
      development are described. Leech embryos undergo spiral cleavage, then produce a
      set of teloblastic stem cells that generate segmented mesoderm and ectoderm. Hau
      Pax3/7A is present as a maternal transcript in both ectodermal and mesodermal
      progenitors, but this pool of early RNA disappears and is replaced by a pattern
      of zygotic transcription restricted to the blast cell progeny of the mesodermal M
      teloblasts. Each mesodermal blast cell clone goes through multiple phases of Hau
      Pax3/7A expression, the last of which is associated with the organogenesis of the
      nephridia and other segment-specific structures. Morpholino-mediated knockdown of
      Hau-Pax3/7A expression causes the mesodermal blast cell clones to undergo
      irregular patterns of morphogenesis that disrupt the segmental organization of
      the germinal plate, and interferes with both the specification and morphological
      differentiation of the mesodermal nephridia. Knockdown of Hau-Pax3/7A in the
      mesoderm can also lead to abnormalities in the formation of the dorsal cavities,
      possibly through indirect effects of this germ layer on neighboring tissues. This
      is the first report of broad mesodermal Pax III expression outside of chordates,
      and raises the possibility that such expression may be a primitive trait
      inherited from the last common ancestor of the bilaterian superphyla.

PMID- 17433286
TI  - Wnt5a functions in planar cell polarity regulation in mice.
AB  - Planar cell polarity (PCP) refers to the polarization of cells within the plane
      of a cell sheet. A distinctive epithelial PCP in vertebrates is the uniform
      orientation of stereociliary bundles of the sensory hair cells in the mammalian
      cochlea. In addition to establishing epithelial PCP, planar polarization is also
      required for convergent extension (CE); a polarized cellular movement that occurs
      during neural tube closure and cochlear extension. Studies in Drosophila and
      vertebrates have revealed a conserved PCP pathway, including Frizzled (Fz)
      receptors. Here we use the cochlea as a model system to explore the involvement
      of known ligands of Fz, Wnt morphogens, in PCP regulation. We show that Wnt5a
      forms a reciprocal expression pattern with a Wnt antagonist, the secreted
      frizzled-related protein 3 (Sfrp3 or Frzb), along the axis of planar polarization
      in the cochlear epithelium. We further demonstrate that Wnt5a antagonizes Frzb in
      regulating cochlear extension and stereociliary bundle orientation in vitro, and
      that Wnt5a(-/-) animals have a shortened and widened cochlea. Finally, we show
      that Wnt5a is required for proper subcellular distribution of a PCP protein,
      Ltap/Vangl2, and that Wnt5a interacts genetically with Ltap/Vangl2 for uniform
      orientation of stereocilia, cochlear extension, and neural tube closure.
      Together, these findings demonstrate that Wnt5a functions in PCP regulation in
      mice.

PMID- 17433289
TI  - The secreted EGF-Discoidin factor xDel1 is essential for dorsal development of
      the Xenopus embryo.
AB  - We show here that a secreted EGF-Discoidin-domain protein, Xenopus Del1 (xDel1),
      is an essential factor for dorsal development in the early Xenopus embryo.
      Knockdown of the xDel1 function causes obvious ventralization of the embryo.
      Conversely, overexpression of xDel1 expands dorsal-marker expression and
      suppresses ventral-marker expression in the gastrula embryo. Forced expression of
      xDel1 dorsalizes ventral marginal zone explants, whereas it weakly induces neural
      differentiation but not mesodermal differentiation in animal caps. The
      dorsalizing activity of xDel1 is dependent on the Discoidin domains and not on
      the RGD motif (which is implicated in its angiogenic activity) or EGF repeats.
      Luciferase assays show that xDel1 attenuates BMP-signaling reporter activity by
      interfering with the pathway downstream of the BMP receptor. Thus, xDel1
      functions as a unique extracellular regulatory factor of DV patterning in early
      vertebrate embryogenesis.

PMID- 17433287
TI  - Wingless/Wnt signal transduction requires distinct initiation and amplification
      steps that both depend on Arrow/LRP.
AB  - Members of the Wg/Wnt family provide key intercellular signals during embryonic
      development and in the maintenance of homeostatic processes, but critical aspects
      of their signal transduction pathways remain controversial. We have found that
      canonical Wg signaling in Drosophila involves distinct initiation and
      amplification steps, both of which require Arrow/LRP. Expressing a chimeric
      Frizzled2-Arrow protein in flies that lack endogenous Wg or Arrow showed that
      this construct functions as an activated Wg receptor but is deficient in signal
      amplification. In contrast, a chimeric Arrow protein containing the dimerization
      domain of Torso acted as a potent amplifier of Wg signaling but could not
      initiate Wg signaling on its own. The two chimeric proteins synergized, so that
      their co-expression largely reconstituted the signaling levels achieved by
      expressing Wg itself. The amplification function of Arrow/LRP appears to be
      particularly important for long-range signaling, and may reflect a general
      mechanism for potentiating signals in the shallow part of a morphogen gradient.

PMID- 17433290
TI  - MF magnitude does not affect body condition, pro-oxidants and anti-oxidants in
      Eurasian kestrel (Falco tinnunculus) nestlings.
AB  - Pylons of utility lines are commonly used by breeding birds as structures for
      supporting their nests. Nesting near power lines, however, exposes adult birds
      and their offspring to the electric and magnetic fields (EMFs) produced by the
      current. Therefore, we searched for possible relationships between the magnetic
      field (MF) magnitude experienced by wild kestrel (Falco tinnunculus) nestlings
      grown on pylons and different health-related variables: body condition, serum
      concentration of carotenoids, reactive oxygen metabolites (ROMs; marker of early
      oxidative damage), serum anti-oxidant capacity (OXY), and the ratio between ROMs
      and OXY (index of oxidative stress). No significant relationships were found
      between the MF magnitude or squared MFs and any of the variables considered.
      Comparisons with values recorded in nestlings from non-exposed nests seem to
      confirm the absence of any effect of exposure to MFs produced by power lines on
      the variables considered.

PMID- 17433291
TI  - Antidepressant-like effect of lamotrigine in the mouse forced swimming test:
      evidence for the involvement of the noradrenergic system.
AB  - Lamotrigine is an anticonvulsant drug that is also effective in the treatment of
      mood disorders, especially bipolar disorder. However, few studies have been
      conducted in animal models of depression to evaluate its mechanism of action. The
      present study investigated the effect of lamotrigine in the forced swimming test
      in mice and the involvement of the noradrenergic system in this effect.
      Lamotrigine (20-30 mg/kg, i.p.) decreased the immobility time in the forced
      swimming test and the number of crossings in the open-field test. In addition,
      the pretreatment of mice with the inhibitor of the enzyme tyrosine hydroxylase,
      alpha-methyl-p-tyrosine (100 or 250 mg/kg), prevented the antidepressant-like
      effect of lamotrigine (30 mg/kg, i.p.) in the forced swimming test. Besides that,
      the pretreatment of mice with prazosin (1 mg/kg, i.p., an alpha1-adrenoceptor
      antagonist) or yohimbine (1 mg/kg, i.p., an alpha2-adrenoceptor antagonist) also
      prevented the anti-immobility effect of lamotrigine (30 mg/kg, i.p.). Moreover,
      the administration of subeffective doses of phenylephrine (5 mg/kg, i.p., an
      alpha1-adrenoceptor agonist) or clonidine (0.06 mg/kg, i.p., an alpha2
      adrenoceptor agonist) was able to potentiate the action of a subeffective dose of
      lamotrigine (10 mg/kg, i.p.) in the forced swimming test. Thus, the present study
      suggests that the antidepressant-like effect of lamotrigine in the forced
      swimming test is related to the noradrenergic system, likely due to an activation
      of alpha1- and alpha2-postsynaptic adrenoceptors.

PMID- 17433292
TI  - Regulator of G protein signaling proteins differentially modulate signaling of mu
      and delta opioid receptors.
AB  - Effects of regulator of G protein signaling (RGS) proteins on mu and delta opioid
      receptors were investigated in HEK293 cells. Co-expression of RGS1, RGS2, RGS4,
      RGS9, RGS10 or RGS19 (Galpha-interacting protein (GAIP)) significantly reduced
      [Tyr-D-Ala-Gly-N-methyl-Phe-Gly-ol]-Enkephalin (DAMGO)-induced inhibition of
      adenylyl cyclase (AC) mediated by mu opioid receptor, but only RGS9 decreased the
      effects of [Tyr-D-Pen-Gly-p-Chloro-Phe-D-Pen]-Enkephalin (DPDPE) mediated by
      delta opioid receptor. When C-tails of the receptors were exchanged (mu/deltaC
      and delta/muC chimeras), RGS proteins decreased delta/muC-mediated AC inhibition,
      but none had significant effects on that via mu/deltaC receptor. Thus, the C
      terminal domains of the receptors are critical for the differential effects of
      RGS proteins, which may be due to differences in receptor-G protein-RGS protein
      interactions in signaling complexes.

PMID- 17433293
TI  - Identification and analysis of in vitro cultured CD45-positive cells capable of
      multi-lineage differentiation.
AB  - We report on a subset of cells that co-purify with CD45-positive/Lineage minus
      (CD45(pos)/Lin(minus)) hematopoietic cells that are capable of in vitro
      differentiation into multi-potential cells including cells with neuroectoderm
      properties. Although these cells are CD45 positive and have properties similar to
      CD45-negative mesenchymal progenitor cells (MPC) derived from bone marrow (BM),
      they are neither hematopoietic cells nor mesenchymal cells. These
      CD45(pos)/Lin(minus) cells can be expanded in vitro, express the stem cell genes
      Oct-4 and Nanog and can be induced to differentiate into endothelial cells,
      osteoblasts, muscle cells and neural cells at frequencies similar to those
      reported for bone marrow mesenchymal cells. Long-term culture of these cells
      followed by transplantation into NOD/SCID mice resulted in positive bone marrow
      stromal cell engraftment but not hematopoietic engraftment, suggesting that
      despite their CD45-positive status these cells do not have the same properties as
      hematopoietic stem cells. Clonal cell analysis determined that the culture period
      caused a broadening in the differentiation potential of the starting population.

PMID- 17433294
TI  - Endothelin-1, endothelin A and B receptor expression and their pharmacological
      properties in GFAP negative human lamina cribrosa cells.
AB  - Primary open angle glaucoma (POAG) is a progressive optic neuropathy,
      characterized, in part by extensive extra cellular matrix remodeling and collapse
      of the lamina cribrosa (LC). Endothelin-1 (ET-1), a potent vasoactive peptide and
      its receptors, endothelin receptor A (ET(A)) and endothelin receptor B (ET(B)),
      have been implicated in glaucomatous optic neuropathy. In this study we examined
      the expression of ET-1 and its receptors in GFAP negative LC cells. RT-PCR
      analysis revealed that LC cells express both ET(A), ET(B) receptors and prepro-
      ET-1, the primary gene transcript of ET-1. A dose-dependent increase in intra
      cellular calcium concentrations was observed in the presence of 1, 10 and 100nM
      ET-1. Increased intracellular calcium concentrations were blocked by the ET(A)
      selective antagonist BQ610 but not by the ET(B) specific antagonist BQ788.
      Desensitization to ET(A)-mediated increase in intracellular calcium was observed
      in LC cells following pre-treatment with ET-1 for 24h. Western blot analysis of
      LC cells treated with ET-1 for 24h revealed a decreased expression of ET(A)
      receptor protein at 1, 10 and 100nM concentrations, while a dose dependent
      increase in the ET(B) receptor was observed with a significant increase at 100nM.
      Quantitative PCR showed a dose-dependent decrease in ET(A) receptor mRNA levels
      and an increase in the mRNA levels of ET(B) receptors. A Griess colorimetric
      assay was used to measure the NO released from LC cells and ET-1 induced a dose
      dependent increase in NO release which was significant at 100nM concentration. ET
      1 induced NO release was significantly blocked by BQ788, an ET(B) selective
      antagonist, and as well as BQ610, an ET(A) selective antagonist. These results
      suggested that human lamina cribrosa cells expressed functional ET(A) and ET(B)
      receptors and their expression and function was altered in response to prolong
      exposure to ET-1. This may have an implication in the normal physiology of LC
      cells and in POAG subjects where elevated levels of ET-1 could impact LC
      function.

PMID- 17433296
TI  - Non-steroidal anti-inflammatory drugs in Parkinson's disease.
AB  - Parkinson's disease (PD) is known to be a chronic and progressive
      neurodegenerative disease caused by a selective degeneration of dopaminergic
      (DAergic) neurons in the substantia nigra pars compacta (SNc). A large body of
      experimental evidence indicates that the factors involved in the pathogenesis of
      this disease are several, occurring inside and outside the DAergic neuron.
      Recently, the role of the neuron-glia interaction and the inflammatory process,
      in particular, has been the object of intense study by the research community. It
      seems to represent a new therapeutic approach opportunity for this neurological
      disorder. Indeed, it has been demonstrated that the cyclooxygenase type 2 (COX-2)
      is up-regulated in SNc DAergic neurons in both PD patients and animal models of
      PD and, furthermore, non-steroidal anti-inflammatory drugs (NSAIDs) pre-treatment
      protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6
      hydroxydopamine (6-OHDA)-induced nigro-striatal dopamine degeneration. Moreover,
      recent epidemiological studies have revealed that the risk of developing PD is
      reduced in humans who make therapeutical use of NSAIDs. Consequently, it is
      hypothesized that they might delay or prevent the onset of PD. However, whether
      or not these common drugs may also be of benefit to those individuals who already
      have Parkinson's disease has not as yet been shown. In this paper, evidence
      relating to the protective effects of aspirin or other NSAIDs on DAergic neurons
      in animal models of Parkinson's disease will be discussed. In addition, the
      pharmacological mechanisms by which these molecules can exert their
      neuroprotective effects will be reviewed. Finally, epidemiological data exploring
      the effectiveness of NSAIDs in the prevention of PD and their possible use as
      adjuvants in the therapy of this neurodegenerative disease will also be examined.

PMID- 17433295
TI  - The PPAR gamma agonist Pioglitazone improves anatomical and locomotor recovery
      after rodent spinal cord injury.
AB  - Traumatic spinal cord injury (SCI) is accompanied by a dramatic inflammatory
      response, which escalates over the first week post-injury and is thought to
      contribute to secondary pathology after SCI. Peroxisome proliferator-activated
      receptors (PPAR) are widely expressed nuclear receptors whose activation has led
      to diminished pro-inflammatory cascades in several CNS disorders. Therefore, we
      examined the efficacy of the PPARgamma agonist Pioglitazone in a rodent SCI
      model. Rats received a moderate mid-thoracic contusion and were randomly placed
      into groups receiving vehicle, low dose or high dose Pioglitazone. Drug or
      vehicle was injected i.p. at 15 min post-injury and then every 12 h for the first
      7 days post-injury. Locomotor function was followed for 5 weeks using the BBB
      scale. BBB scores were greater in treated animals at 7 days post-injury and
      significant improvements in BBB subscores were noted, including better toe
      clearance, earlier stepping and more parallel paw position. Stereological
      measurements throughout the lesion revealed a significant increase in rostral
      spared white matter in both Pioglitazone treatment groups. Spinal cords from the
      high dose group also had significantly more gray matter sparing and motor neurons
      rostral and caudal to epicenter. Thus, our results reveal that clinical treatment
      with Pioglitazone, an FDA-approved drug used currently for diabetes, may be a
      feasible and promising strategy for promoting anatomical and functional repair
      after SCI.

PMID- 17433297
TI  - Zinc-mediated neuronal death is dependent on Trk activation.
AB  - Zinc release is a primary mediator of neuronal death. Here we show that zinc
      mediated death of neurons in vitro is dependent on nerve growth factor (NGF)
      stimulation and does not occur in response to exposure to leukemia inhibitory
      factor. NGF priming is regulated, not by the traditional neurotrophin death
      receptor, p75NTR, but by TrkA, in a protein- and mRNA synthesis-dependent manner.
      Furthermore, Trk signaling promotes raised free intracellular zinc, mediating
      neuronal death after extracellular application of zinc. Thus, regulators of Trk
      signaling provide attractive targets for future treatment of zinc-associated
      neurological diseases, including stroke, epilepsy and brain trauma.

PMID- 17433298
TI  - Inhibition of glycogen synthase kinase-3 suppresses the onset of symptoms and
      disease progression of G93A-SOD1 mouse model of ALS.
AB  - Glycogen synthase kinase (GSK)-3 has recently been implicated in the pathogenesis
      of neurodegenerative diseases. Although the neuroprotective effects of GSK-3
      inhibitors in Alzheimer's disease have been established, their effects on
      amyotrophic lateral sclerosis (ALS) have not been well defined. This study was
      undertaken to evaluate the effects of GSK-3 inhibition in the G93A-SOD1 mouse
      model of ALS. Groups of G93A-SOD1 mice were treated with varying concentrations
      of GSK-3 inhibitor VIII, a specific GSK-3 inhibitor that crosses the BBB,
      intraperitoneally 5 days a week after 60 days of age. The GSK-3 inhibitor VIII
      treatment significantly delayed the onset of symptoms and prolonged the life span
      of the animals, and inhibited the activity of GSK-3 in a concentration-dependent
      manner. Furthermore, this treatment preserved survival signals and attenuated
      death and inflammatory signals. These data suggest that GSK-3 plays an important
      role in the pathogenic mechanisms of ALS and that inhibition of GSK-3 could be a
      potential therapeutic candidate for ALS.

PMID- 17433299
TI  - Reduced dendrite growth and altered glutamic acid decarboxylase (GAD) 65- and 67
      kDa isoform protein expression from mouse cortical GABAergic neurons following
      excitotoxic injury in vitro.
AB  - The vulnerability of brain cells to neurologic insults varies greatly, depending
      on their neuronal subpopulation. However, cells surviving pathological insults
      such as ischemia or brain trauma may undergo structural changes, e.g., altered
      process growth, that could compromise brain function. In this study, we examined
      the effect of glutamate excitotoxicity on dendrite growth from surviving cortical
      GABAergic neurons in vitro. Glutamate exposure did not affect GABAergic neuron
      viability, however, it significantly reduced dendrite growth from GABAergic
      neurons. This effect was blocked by the AMPA receptor antagonists NBQX and CFM-2,
      and mimicked by AMPA, but not NMDA. Glutamate excitotoxicity also caused an NMDA
      receptor-mediated decrease in the GABA synthesizing enzyme glutamic acid
      decarboxylase (GAD65/67) immunoreactivity from GABAergic neurons, measured using
      immunocytochemical and Western blot techniques. GAD is necessary for GABA
      synthesis; however, reduction of GABA by 3-mercaptopropionic acid (3-MPA), which
      inhibits GABA synthesis, did not alter dendrite growth. These results suggest
      that GABAergic cortical neurons are relatively resistant to excitotoxic-induced
      cell death, but they can display morphological and biochemical alterations which
      may impair their function.

PMID- 17433300
TI  - Schistosoma japonicum eggs modulate the activity of CD4+ CD25+ Tregs and prevent
      development of colitis in mice.
AB  - Crohn's disease (CD) is considered to be caused by a disorder of the immune
      system and helminth infections may interact with development of the disease. We
      induced colitis in mice by trinitrobenzenesulfonic acid (TNBS) and observed the
      effects of intraperitoneally injected eggs of Schistosoma japonicum on the course
      of the disease. The inflammation in the colon was reduced in egg-treated mice and
      secretion of IFN-gamma (a Th1 cytokine) by cultured spleen cells in vitro was
      greatly suppressed, and of IL-4, IL-5 and IL-10 (Th2 cytokines) significantly
      elevated after egg injection. Also, the percentage of regulatory T-cells (Tregs)
      was increased in the spleens of egg-exposed mice with TNBS-induced colitis
      compared to non-egg exposed animals. The data suggest that Tregs may be activated
      by S. japonicum eggs and play a role in restoring immune disorders in TNBS
      induced colitis of mice.

PMID- 17433301
TI  - Real-time PCR versus conventional PCR for malaria parasite detection in low-grade
      parasitemia.
AB  - We have optimized a faster and cheaper real-time PCR and developed a conventional
      genus specific PCR based on 18S rRNA gene to detect malaria parasites in low
      grade parasitemias. Additionally, we compared these PCRs to the OptiMAL-IT test.
      Since there is no consensus on choice of standard quantitative curve in real-time
      assays, we decided to investigate the performance of parasite DNA from three
      different sources: "genome", amplicon and plasmid. The amplicon curve showed the
      best efficiency in quantifying parasites. Both PCR assays detected 100% of the
      clinical samples tested; the sensitivity threshold was 0.5 parasite/mul and no
      PCR positive reaction occurred when malaria parasites were not present.
      Conversely, if OptiMAL-IT were employed for malaria diagnosis, 30% of false
      negative results could be expected. We conclude that PCR assays have potential
      for detecting malaria parasites in asymptomatic infections, in evaluation of
      malaria vaccine molecule candidates, for screening blood donors, especially in
      endemic areas, or even in monitoring malaria therapy.

PMID- 17433302
TI  - Amblyomma triste (Koch, 1844) (Acari: Ixodidae) ovaries: an ultrastructural
      analysis.
AB  - This study presents an ultrastructural analysis of the ovary of the tick,
      Amblyomma triste. The ovary of this species is of the panoistic type that is,
      without nursing and follicular cells. It is composed of a layer of epithelial
      cells forming a wall and of germinative cells that generate the oocytes which
      remain attached to the external margin of this wall by a multicellular pedicel.
      The different developmental stages in the oocytes had been described by Oliveira
      et al. [Oliveira, P.R., Bechara, G.H., Camargo-Mathias, M.I., 2006. Amblyomma
      triste (Koch, 1844) (Acari: Ixodidae): Morphological description of the ovary and
      of vitellogenesis. Experimental Parasitology 113, 179-185]. The results of the
      investigation suggest that besides exogenous production of vitellogenic elements,
      endogenous production can take place simultaneously, contributing to the
      development and growth of the oocytes.

PMID- 17433303
TI  - Mechanism of vitamin D3-induced transcription of phospholipase D1 in HaCat human
      keratinocytes.
AB  - 1alpha,25-Dihydroxyvitamin D(3) (VitD(3)) increases protein and gene expression
      of phospholipase D1 (PLD1), but not PLD2, in HaCaT human keratinocytes. We show
      that VitD(3) increases PLD1 gene expression through a vitamin D responsive
      element (VDRE) on the 5' PLD1 promoter (-260 bp to -246 bp from exon 1). Similar
      results were obtained by transfecting VitD(3) receptor (VDR) into HEK293 cells,
      which are originally VitD(3)-unresponsive. Electrophoresis mobility shift assays
      (EMSA) and chromatin immunoprecipitation (CHIP) assays showed that the complex of
      VitD(3), VDR and retinoid X receptor alpha (RXRalpha) binds to the VDRE and
      increases PLD1 gene expression in HaCaT cells.

PMID- 17433304
TI  - Pancreatic islet beta-cell and oxidative stress: the importance of glutathione
      peroxidase.
AB  - Pancreatic beta-cell function continuously deteriorates in type 2 diabetes
      despite optimal treatment regimens, which has been attributed to hyperglycemia
      itself via formation of excess levels of reactive oxygen species (ROS).
      Glutathione peroxidase GPx), by virtue of its ability to catabolize both H(2)O(2)
      and lipid peroxides, is uniquely positioned to protect tissues from ROS. The
      level of this antioxidant in beta cells is extremely low and overexpression of
      GPx in islets provides enhanced protection against oxidative stress. This
      suggests that GPx mimetics may represent a valuable ancillary treatment that
      could add a novel layer of protection for the beta-cell.

PMID- 17433305
TI  - Arginine 357 of SecY is needed for SecA-dependent initiation of preprotein
      translocation.
AB  - The Escherichia coli SecYEG complex forms a transmembrane channel for both
      protein export and membrane protein insertion. Secretory proteins and large
      periplasmic domains of membrane proteins require for translocation in addition
      the SecA ATPase. The conserved arginine 357 of SecY is essential for a yet
      unidentified step in the SecA catalytic cycle. To further dissect its role, we
      have analysed the requirement for R357 in membrane protein insertion. Although
      R357 substitutions abolish post-translational translocation, they allow the
      translocation of periplasmic domains targeted co-translationally by an N-terminal
      transmembrane segment. We propose that R357 is essential for the initiation of
      SecA-dependent translocation only.

PMID- 17433306
TI  - Stress-induced rearrangements of cellular networks: Consequences for protection
      and drug design.
AB  - The complexity of the cells can be described and understood by a number of
      networks such as protein-protein interaction, cytoskeletal, organelle,
      signalling, gene transcription and metabolic networks. All these networks are
      highly dynamic producing continuous rearrangements in their links, hubs, network
      skeleton and modules. Here we describe the adaptation of cellular networks after
      various forms of stress causing perturbations, congestions and network damage.
      Chronic stress decreases link-density, decouples or even quarantines modules, and
      induces an increased competition between network hubs and bridges. Extremely long
      or strong stress may induce a topological phase transition in the respective
      cellular networks, which switches the cell to a completely different mode of
      cellular function. We summarize our initial knowledge on network restoration
      after stress including the role of molecular chaperones in this process. Finally,
      we discuss the implications of stress-induced network rearrangements in diseases
      and ageing, and propose therapeutic approaches both to increase the robustness
      and help the repair of cellular networks.

PMID- 17433307
TI  - Tunneling nanotubes: a new route for the exchange of components between animal
      cells.
AB  - Recently, highly sensitive nanotubular structures mediating membrane continuity
      between mammalian cells have been discovered. With respect to their peculiar
      architecture, these membrane channels were termed tunneling nanotubes (TNTs).
      TNTs could form de novo between animal cells leading to the generation of complex
      cellular networks. They have been shown to facilitate the intercellular transfer
      of organelles as well as, on a limited scale, of membrane components and
      cytoplasmic molecules. It has been proposed that TNTs represent a novel and
      general biological principle of cell-to-cell communication and it becomes
      increasingly apparent that they fulfill important functions in the physiological
      processes of multicellular organisms.

PMID- 17433308
TI  - Shedding of the p75NTR neurotrophin receptor is modulated by lipid rafts.
AB  - Protein ectodomain shedding is the proteolytic release of the extracellular
      domain of membrane-bound proteins. Neurotrophin receptor p75(NTR) is known to be
      affected by shedding. The present work provides evidence, in rat brain
      synaptosomes, that p75(NTR) is present in detergent-resistant membranes (DRM),
      also known as lipid rafts, only in its full-length form. Disrupting the integrity
      of lipid rafts causes solubilization of p75(NTR) after detergent treatment and
      enhancement of the shedding. Analyses of the enzymes described as being
      responsible for p75(NTR) shedding, i.e. tumor necrosis factor alpha convertase
      (TACE) and presenilin-1 (PS1), revealed that TACE is absent in DRM, while
      variable proportions of the C-terminal and N-terminal fragments of PS1 are found.
      In summary, our results point to a role of lipid rafts in the modulation of the
      shedding of the p75(NTR) receptor.

PMID- 17433309
TI  - Transfection and expression of plasmid DNA in plant cells by an arginine-rich
      intracellular delivery peptide without protoplast preparation.
AB  - The delivery and expression of exogenous genes in plant cells have been of
      particular interest for plant research and biotechnology. Here, we present
      results demonstrating a simple DNA transfection system in plants. Short arginine
      rich intracellular delivery peptide, a protein transduction domain, was capable
      of delivering plasmid DNA into living plant cells non-covalently. This peptide
      mediated DNA delivery conferred several advantages, such as nuclear targeting,
      non-toxic effect, and ease of preparation without protoplast formulation. Thus,
      this novel technology shall provide a powerful tool to investigate gene function
      in vivo, and lay the foundation for the production of transgenic plants in
      future.

PMID- 17433310
TI  - Diverse stress signals activate the C1 subgroup MAP kinases of Arabidopsis.
AB  - Mitogen-activated protein kinase (MAPK) cascades play an important role in
      mediating stress responses in plants. In Arabidopsis, 20 MAPKs have been
      identified and classified into four major groups (A-D). Little is known about the
      role of group C MAPKs. We have studied the activation of Arabidopsis subgroup C1
      MAPKs (AtMPK1/AtMPK2) in response to mechanical injury. An increase in their
      kinase activity was detected in response to wounding that was blocked by
      cycloheximide. Jasmonic acid (JA) activated AtMPK1/AtMPK2 in the absence of
      wounding. Wound and JA-induction of AtMPK1/2 kinase activity was not prevented in
      the JA-insensitive coi1 mutant. Other stress signals, such as abscisic acid (ABA)
      and hydrogen peroxide, activated AtMPK1/2. This report shows for the first time
      that regulation of AtMPK1/2 kinase activity in Arabidopsis might be under the
      control of signals involved in different kinds of stress.

PMID- 17433311
TI  - Involvement of FpTRP26, a thioredoxin-related protein, in oxalic acid-resistance
      of the brown-rot fungus Fomitopsis palustris.
AB  - Brown-rot fungus Fomitopsis palustris grows vigorously at high concentrations of
      oxalic acid (OA), which is fungal metabolite during wood decay. We isolated a
      cDNA FpTRP26 from F. palustris by functional screening of yeast transformants
      with cDNAs grown on plates containing OA. FpTRP26 conferred a specific resistance
      to OA on the transformant. OA-content in transformants grown with 2mM OA
      decreased by 65% compared to that of the control. The amount of FpTRP26
      transcript in F. palustris amplified with increasing OA-accumulation, and was
      maintained at high levels even in the stationary phase. Its transcription in F.
      palustris was inducible in response to exogenously added OA. These results
      suggest that FpTRP26 is involved in the OA-resistance in F. palustris.

PMID- 17433313
TI  - Comparison of urinary and recombinant human chorionic gonadotropin during
      ovulation induction in intrauterine insemination cycles: a prospective randomized
      clinical trial.
AB  - OBJECTIVES: To compare the in vivo effectiveness of recombinant (r) hCG with
      urinary (u) hCG during controlled ovarian hyperstimulation and intrauterine
      insemination (COH-IUI) cycles. DESIGN: Prospective controlled clinical study.
      SETTING: Private IVF center. PATIENT(S): Two hundred eighty-four subjects
      undergoing COH-IUI cycles. INTERVENTIONS(S): Women were randomized into receiving
      r-hCG or u-hCG for final maturation and induction of ovulation. MAIN OUTCOME
      MEASURE(S): Clinical pregnancy rate and outcome of pregnancy. RESULT(S):
      Background characteristics were similar in the two groups studied except for a
      slight difference in the mean duration of infertility (3.0 vs. 2.3). There was no
      significant difference in the number of follicles > or =16 mm, mean peak E(2), or
      mean 1-week P levels between the two groups. The clinical pregnancy rate was
      27.1% in the recombinant group compared with 28.5% in the urinary group. The
      outcome of pregnancy was similar in both groups. CONCLUSION(S): Recombinant hCG
      was found to be as effective as u-hCG in achieving pregnancy during COH-IUI
      cycles. This is in agreement with earlier studies on the effectiveness of r-hCG
      in IVF cycles.

PMID- 17433314
TI  - The use and misuse of matching in case-control studies: the example of polycystic
      ovary syndrome.
AB  - Matching control selection strategies are often used in polycystic ovary syndrome
      case-control studies; however, they are infrequently used in an appropriate
      fashion. When properly applied, matching may offer improved study precision, but
      this is highly contingent on the causal pathway under consideration, strength of
      the associations between the matching variable and both the risk factor of
      interest and polycystic ovary syndrome, and the use of an appropriate stratified
      data analysis.

PMID- 17433312
TI  - Prevalence of sexually transmissible pathogens in semen from asymptomatic male
      infertility patients with and without leukocytospermia.
AB  - OBJECTIVE: To determine the prevalence of pathogens that cause sexually
      transmitted infections (STIs) in semen from asymptomatic male infertility
      patients with and without leukocytospermia (LCS), and associations between STIs,
      inflammatory markers, and other semen variables. DESIGN: Retrospective,
      controlled study. SETTING: Academic Medical Center. PATIENT(S): Two hundred and
      forty-one male infertility patients undergoing routine semen analysis: 132 with
      LCS, and 109 without LCS. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The DNA
      from STI pathogens (human papillomavirus [HPV], cytomegalovirus [CMV], herpes
      simplex virus [HSV], human herpesvirus type 6 [HHV-6], Epstein-Barr virus [EBV],
      hepatitis B virus [HBV], and Chlamydia trachomatis [CT]), routine semen
      parameters, and markers of accessory gland and epididymal function and
      inflammation. RESULT(S): The DNA from STI pathogens was detected in 45/241
      (18.7%) of the samples (CMV, 8.7%; HPV, 4.5%; HHV-6, 3.7%; HSV, 3.7%; CT, 2.5%;
      EBV, 0.4%; and HBV, 0%), with no difference in prevalence between the LCS and non
      LCS groups. The DNA of STI pathogens in semen was associated with a decrease in
      sperm concentration, motile sperm concentration, total sperm count, and neutral
      alpha-glucosidase concentration, whereas LCS was associated with a decrease in
      total sperm count, percent normal forms, and fructose concentration.
      CONCLUSION(S): The DNA of STI pathogens was detected in semen from a high
      percentage of asymptomatic male infertility patients, and was associated with
      poor semen quality. Efforts to diagnose and treat subclinical genital-tract
      infections should be intensified.

PMID- 17433316
TI  - The position of transferred air bubbles after embryo transfer is related to
      pregnancy rate.
AB  - OBJECTIVE: The possibility to visualize the transfer air bubbles is one of the
      main benefits of ultrasonographic-guided embryo transfer. The objective of this
      study was to analyze the relation between the position of the air bubbles and
      pregnancy rates. DESIGN: Prospective data-analysis. SETTING: University fertility
      clinic. PATIENT(S): IVF and intracytoplasmic sperm injection patients.
      INTERVENTION(S): Transabdominal ultrasonographic guidance at embryo transfer.
      MAIN OUTCOME MEASURE(S): Pregnancy rate, length endometrial plate, distance
      catheter to fundus, distance air bubbles to fundus. RESULT(S): Analysis of 367
      consecutive ultrasonographic-guided embryo transfers following IVF or
      intracytoplasmic sperm injection treatment. Both absolute and relative position
      of the air bubbles were significantly closer to the fundus in patients who became
      pregnant compared with patients who did not become pregnant. When the relative
      position of the air bubbles was in the fundal half of the endometrial plate
      pregnancy rates were significantly higher compared with the lower half of the
      endometrial plate, 43.0% and 24.4%, respectively, P=.002. Multiple regression
      analysis revealed the relative position as an independently associated
      determinant for pregnancy. CONCLUSION(S): The position of the air bubbles after
      embryo transfer is related to pregnancy rate; the highest pregnancy rates are
      found when the air bubbles end up closer to the fundus.

PMID- 17433315
TI  - Comparison of two doses of metformin (2.5 and 1.5 g/day) for the treatment of
      polycystic ovary syndrome and their effect on body mass index and waist
      circumference.
AB  - Fifty-six women with body mass index (BMI) greater than 27 were randomly divided
      into two groups receiving different doses of metformin (2.5 g and 1.5 g/day) for
      the treatment of polycystic ovary syndrome to assess its effects on BMI and waist
      circumference. Although after 6 months of treatment both groups had a significant
      reduction in those indices, the intergroup variation proved the higher dose to be
      more efficient.

PMID- 17433317
TI  - Anxiety and sexual stress in men and women undergoing infertility treatment.
AB  - OBJECTIVE: To better understand the specific nature of the relationship between
      anxiety and sexual infertility-related stress in men and women. DESIGN:
      Prospective study. SETTING: University-affiliated teaching hospital. PATIENT(S):
      Consecutively referred patients referred for in vitro fertilization and
      intrauterine insemination (306 women, 295 men). INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Fertility Problem Inventory (FPI), Beck Anxiety Inventory
      (BAI). RESULT(S): Women reported greater anxiety and sexual infertility stress
      than men. However, men and women showed a similar pattern in the way anxiety
      symptoms were related to sexual infertility stress, with subjective anxiety and
      autonomic anxiety having the strongest relationship. Anxiety symptoms accounted
      for a significant proportion of the variance in sexual infertility stress for
      both sexes and predicted sexual stress to a considerable degree in men.
      CONCLUSION(S): Although this study found that there is more similarity than
      difference in how men and women experience anxiety and sexual infertility stress,
      the strong linkage between anxiety and sexual stress in men was surprising,
      because men tend to report less sexual stress and also less anxiety. Sexual
      stress among infertile men may be more closely tied to performance anxiety rather
      than to a more general deterioration in sexual satisfaction associated with
      infertility.

PMID- 17433318
TI  - What is happening to the price of eggs?
AB  - OBJECTIVE: To survey reproductive medical programs that are members of the
      Society for Assisted Reproductive Technology (SART) to ascertain their ovum donor
      compensation rates. DESIGN: Survey. SETTING: Society of Assisted Reproductive
      Technology member programs. PATIENT(S): None applicable. INTERVENTION(S): One
      page anonymous e-mail survey returned by FAX within 1 week. MAIN OUTCOME
      MEASURE(S): Clinics were asked if they have a donor oocyte program, and, if yes,
      their standard compensation rate. In addition, clinics were asked if there are
      other variables that increase compensation rates, and, if yes, the maximum
      compensation. Data were analyzed according to U.S. geographic regions. RESULT(S):
      Over half SART clinics (53%, 207 out of 394) responded to the survey, with 191
      (92%, 191 out of 207) having a donor oocyte program. The national average for
      standard donor compensation was $4,217, with a maximum payment average of $4,576.
      Geographic location affected compensation rates, with highest reported standard
      mean compensation in the East/Northeast ($5,018) and West regions ($4,890), and
      lowest in the Northwest ($2,900). CONCLUSION(S): The national average for
      compensating oocyte donors in reporting SART programs is approximately $4,200.

PMID- 17433319
TI  - A comparison of follicular response of ovaries to ovulation induction after
      laparoscopic ovarian cystectomy or fenestration and coagulation versus normal
      ovaries in patients with endometrioma.
AB  - In a comparison of follicular responses to controlled ovarian hyperstimulation
      (COH) between normal ovaries and ovaries previously treated by different
      laparoscopic techniques for ovarian endometrioma in 65 patients with unilateral
      endometrioma, laparoscopic ovarian fenestration and coagulation was performed in
      24 cases (group 1) and laparoscopic ovarian cystectomy in the other 41 (group 2).
      In 16 patients with bilateral endometrioma (group 3), cystectomy was done in one
      ovary and fenestration and coagulation in the contralateral side. The results
      indicate that the response of ovaries to COH after laparoscopic ovarian
      cystectomy or fenestration and coagulation was the same and that there was no
      difference in response to COH between normal ovaries and those operated on by the
      laparoscopic techniques mentioned above.

PMID- 17433320
TI  - Spontaneous ovarian hyperstimulation in a pregnant woman with hypothyroidism.
AB  - OBJECTIVE: This report describes an unusual case in which a naturally conceived
      pregnancy is associated with spontaneous ovarian hyperstimulation and
      hypothyroidism. DESIGN: Case report. SETTING: University medical center.
      PATIENT(S): A 30-year-old pregnant woman with abdominal pain and distension
      caused by ovarian hyperstimulation. INTERVENTION(S): Medical management and
      laparotomy. MAIN OUTCOME MEASURE(S): Incomplete regression after 3 months.
      RESULT(S): Thyroid-stimulating hormone level was elevated. Hormonal studies
      confirmed hypothyroidism with spontaneous ovarian hyperstimulation. She was given
      levothyroxine 200 mug/d. Results of the hormonal tests for thyroid function were
      normal 3 months after treatment, but in this case the ovarian cysts did not
      regress completely until delivery. Laparotomy and cesarean section were done for
      both diagnosis and treatment. Ten weeks after delivery ovarian cysts regressed
      completely. CONCLUSION(S): Thyroid hormone replacement seems to be the best
      therapeutic approach in some patients, but, in some, complete resolution of the
      ovarian cysts does not occur after 3 months.

PMID- 17433321
TI  - Frequency of human sperm carrying structural aberrations of chromosome 1
      increases with advancing age.
AB  - OBJECTIVE: To investigate the association between male age and the frequency of
      sperm with de novo structural chromosomal abnormalities. DESIGN: Semen specimens
      collected from two groups of 10 healthy, nonsmoking men, aged 22-28 and 65-80
      years, were analyzed with the use of a multicolor fluorescence in situ
      hybridization assay for detecting breaks, segmental duplications and deletions,
      and aneuploidy and diploidy involving chromosome 1. SETTING: Healthy volunteer
      workers and retirees from a government research environment. MAIN OUTCOME
      MEASURE: Sperm carrying numerical and structural chromosomal abnormalities.
      RESULT(S): We detected significant increases in the frequency of sperm carrying
      breaks and segmental duplications and deletions of chromosome 1 among older men
      compared with younger men. Older men carried twice the frequency of sperm with
      segmental duplications and deletions of chromosome 1. The frequency of sperm
      carrying breaks within the 1q12 fragile-site region nearly doubled in older men.
      In contrast to female gametes, there was no effect of age on the frequency of
      sperm with numerical chromosomal abnormalities. CONCLUSION: Our findings suggest
      that advancing male age is associated with a gradual and significant increase in
      the risk of fathering children with various chromosomal defects such as segmental
      aneusomy syndromes.

PMID- 17433322
TI  - Two decades of universal hepatitis B vaccination in taiwan: impact and
      implication for future strategies.
AB  - BACKGROUND & AIMS: Following the world's first successful implementation of a
      universal hepatitis B virus (HBV) vaccination program for infants in Taiwan 20
      years ago, we performed this study to evaluate the long-term protection afforded
      by HBV vaccination and to rationalize further prevention strategies. METHODS: HBV
      seromarkers, including hepatitis B surface antigen (HBsAg) and antibodies to
      HBsAg (anti-HBs) and core antigen (anti-HBc), were studied in 18,779 subjects
      from neonates to adults below 30 years of age in 2004. The birth cohort effect
      was evaluated by comparing the results of the same birth cohorts at different
      ages among this survey and the previous 1984, 1989, 1994, and 1999 surveys.
      RESULTS: The seropositive rates for HBsAg, anti-HBs, and anti-HBc were 1.2%,
      50.5%, and 3.7%, respectively, in those born after the vaccination program (<20
      years of age) in 2004. A positive maternal HBsAg status was found in 89% of the
      HBsAg seropositive subjects born after the vaccination program. The absence of an
      increase in HBsAg seropositive subjects at different ages in the same birth
      cohorts born after the vaccination program implied no increased risk of
      persistent HBV infection with aging. CONCLUSIONS: Universal HBV vaccination
      provides long-term protection up to 20 years, and a universal booster is not
      indicated for the primary HBV vaccinees before adulthood. Maternal transmission
      is the primary reason for vaccine failure and is the challenge that needs to be
      addressed in future vaccination programs. This may include an appropriate
      hepatitis B immunoglobulin administration strategy for high-risk infants and
      involve efforts to minimize noncompliance.

PMID- 17433323
TI  - Late-onset Wilson's disease.
AB  - BACKGROUND & AIMS: The clinical symptoms and age at onset of Wilson's disease
      (WD) are highly variable. This study investigated patients who became symptomatic
      at >40 years of age. METHODS: Clinical features, laboratory data, and mutation
      analysis were evaluated in 46 (3.8%) of 1223 patients who were investigated in a
      multinational study on genotype-phenotype correlations (1053 index patients, 170
      siblings) who were >40 years of age at onset of symptoms and, in 2 asymptomatic
      siblings, diagnosed at >40 years of age. RESULTS: Thirty-one patients presented
      with neurologic symptoms (mean age, 44.5 years; range, 40-52; male/female,
      14/17), 15 presented with liver disease (mean age, 47.1 years; range, 40-58;
      male/female, 6/9), and 2 were asymptomatic siblings. Hepatic copper content was
      measured in 17 patients and was above 250 microg/g dry weight in 13. One patient
      with hepatic presentation had "fulminant" WD, the remaining 14 abnormal liver
      function tests and/or hepatomegaly. Liver biopsy specimens were available in 13
      patients presenting with liver disease (cirrhosis, 10; chronic hepatitis, 2;
      steatosis, 1; no abnormalities, 1) and in 14 neurologic patients (cirrhosis, 9;
      advanced fibrosis, 1; chronic hepatitis, 2; no abnormalities, 2). Twenty-seven of
      the 46 index cases had mutations on both chromosomes (including 13
      H1069Q/H1069Q), 13 on just 1 chromosome. CONCLUSIONS: Late-onset WD is a
      frequently overlooked condition. The diagnostic features and the frequency of
      late-onset WD gene mutations were not different than in patients with an earlier
      onset of disease. Factors other than ATP7B mutations may modify the phenotypic
      presentation of WD.

PMID- 17433324
TI  - Telomerase deletion limits progression of p53-mutant hepatocellular carcinoma
      with short telomeres in chronic liver disease.
AB  - BACKGROUND & AIMS: During early stages of carcinogenesis most human epithelial
      cancers including hepatocellular carcinoma (HCC) have been observed to transit
      through a "crisis" stage characterized by telomere shortening, loss of p53
      checkpoint function, and a sharp increase in aneuploidy. The function of
      telomerase during in vivo hepatocarcinogenesis has not been studied in this
      genetic context. METHODS: Here we generated a mouse model in which HCC was
      induced by chronic organ damage (HBs-AG transgene) in the presence of telomere
      shortening and p53 deletion. Tumor development was analyzed in late-generation
      telomerase knockout mice (mTERC(-/-)) and littermates, genetically rescued for
      telomerase gene expression (mTERC(+/-)). RESULTS: The formation of HCCs was
      strongly suppressed in mTERC(-/-) mice compared to mTERC(+/-) siblings
      correlating with reduced rates of tumor cell proliferation and elevated rates of
      tumor cell apoptosis. Although the prevalence of short telomeres was similar in
      chronically damaged liver of both cohorts, mTERC(-/-) HCC developed increased
      levels of DNA damage and aneuploidy compared to mTERC(+/-) HCC. CONCLUSIONS: This
      study provides direct evidence that telomerase is a critical component for in
      vivo progression of p53 mutant HCC with short telomeres in the chronically
      damaged liver. In this molecular context, telomerase limits the accumulation of
      telomere dysfunction, the evolution of excessive aneuploidy, and the activation
      of p53-independent checkpoints suppressing hepatocarcinogenesis.

PMID- 17433325
TI  - Endoscopic therapy for barrett's high-grade dysplasia: entering the therapeutic
      arena.

PMID- 17433326
TI  - A health assessment of high status Christian burials recovered from the Roman
      Byzantine archeological site of Elaiussa Sebaste, Turkey.
AB  - The purpose of this study is to assess the state of health of 116 individuals
      whose remains were excavated from Byzantine period burials underneath the floor
      of an important Christian basilica from the site of Elaiussa Sebaste, Turkey.
      Elaiussa Sebaste was a Mediterranean coastal community, which began as a Roman
      town and continued as an early Christian Byzantine community until the end of the
      7th century AD. The burials date from the middle of the 6th through the middle of
      the 7th centuries AD. We attempt to determine how high social status has
      influenced the type and frequency of skeletal lesions exhibited in this sample.
      All strata of this population show a number of chronic and acute health problems
      as indicated by skeletal lesions. Yet, only the frequency of degenerative joint
      disease (DJD) differs by sex, with males exhibiting a higher rate of DJD than
      females, p=0.09. There is no difference in the frequency of trauma among adult
      males and females. Non-specific skeletal lesions (cribra orbitalia, porotic
      hyperostosis, and periostitis) often associated with dietary and general
      stressors, but also with specific systemic diseases, are common in both sexes.
      The sub-adults primarily exhibit periostitis of the long bones and do not show
      skeletal lesions specific to malaria. It seems that high social ranking did not
      prevent serious ailments from affecting the health of individuals living in the
      Elaiussa Sebaste community.

PMID- 17433327
TI  - Modern human origins in Australasia: testing the predictions of competing models.
AB  - The evolutionary background to the emergence of modern humans remains
      controversial. Four models have been proposed to explain this process and each
      has clearly definable and testable predictions about the geographical origins of
      early Australians and their possible biological interaction with other
      Pleistocene populations. The present study considers the phenetic affinities of
      early Australians from Kow Swamp (KS 1 and KS 5) and Keilor to Pleistocene
      Africans and Asians from calvarial dimensions. The study includes analyses
      employing log-transformed and size-corrected (Mosimann variables) data. The
      strongest signals to emerge are as follows: (1) a phenetic pattern in which
      Australians are most like each other, (2) all three crania possess a mosaic of
      archaic and modern features, (3) Kow Swamp crania also show strong affinities to
      archaic remains, (4) Keilor is more modern than KS 1 and KS 5 and (5) Keilor
      shows affinities to Pleistocene East Asian modern crania (Liujiang and Upper Cave
      101) providing evidence for a broad regional morphology. The results refute the
      predictions of multi-species replacement models for early Australians but are
      consistent with single-species models. Combined with published evidence from DNA,
      the present study indicates that the Assimilation model presently offers the best
      explanation for the origins of Pleistocene Australians.

PMID- 17433328
TI  - Testosterone levels and cognitive functioning in women with polycystic ovary
      syndrome and in healthy young women.
AB  - We investigated the possible influence of testosterone (T) on cognitive
      functioning in women with polycystic ovary syndrome (PCOS), an endocrine disorder
      associated with elevated levels of free testosterone (free T). Performance on a
      battery of neuropsychological tests in 29 women with elevated free T levels due
      to PCOS was compared to the performance of 22 age- and education-matched, healthy
      control women with free T levels in the normal female range. Women with PCOS had
      significantly higher levels of free T (estimated by the free androgen index) and
      demonstrated significantly worse performance on tests of verbal fluency, verbal
      memory, manual dexterity, and visuospatial working memory than the healthy
      control women. No differences between the groups were found on tests of mental
      rotation, spatial visualization, spatial perception, or perceptual speed. These
      results suggest that, in women, elevations in free T may be associated with
      poorer performance on cognitive tasks that tend to show a female advantage.

PMID- 17433329
TI  - Embedded Model Control: outline of the theory.
AB  - Embedded Model Control allows one to proceed systematically from fine plant
      dynamics and control requirements to the Embedded Model (EM), which is the core
      of control design and algorithms. The model defines three interconnected parts:
      the controllable dynamics, the disturbance class to be rejected and the neglected
      dynamics. Controllable and disturbance dynamics must be observable from the plant
      measurements. Control algorithms are designed around the first two parts, while
      stability and performance are constrained by the third one. The key design issue
      is discriminating between driving noise and neglected dynamics, to guarantee
      updating disturbance in view of its rejection. To this end, concept and equations
      of the 'error loop' are outlined: it maps error sources to performance and shows
      how to discriminate destabilizing sources, while meeting performance
      requirements. An introductory example with analytical and simulated results
      illustrates the design steps.

PMID- 17433330
TI  - Relation of sleep-disordered breathing to carotid plaque and intima-media
      thickness.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) is associated with clinical
      cardiovascular disease (CVD), but its relation to subclinical atherosclerosis
      remains to be determined. METHODS: We analyzed the cross-sectional associations
      of SDB, measured by the respiratory disturbance index (RDI), a hypoxemia index,
      and an arousal index, with carotid plaque and carotid intima-media thickness
      (IMT), measured by ultrasound. The sample included 985 participants in the Sleep
      Heart Health Study (mean age-62, median RDI-8.7) with no history of coronary
      heart disease and stroke, of whom 396 had evidence of a carotid plaque. RESULTS:
      As compared with the first quartile of the RDI (0-1.2), the crude odds ratio for
      carotid plaque was 1.14, 1.27, and 1.48 for the second (1.3-4.1), third (4.2
      10.7), and fourth (>10.7) quartile, respectively. After adjustment for CVD risk
      factors, the corresponding odds ratios were reduced (1.00, 1.04, 1.07, and 1.25).
      Similarly, the unadjusted mean carotid IMT increased with RDI, but adjusted means
      (mm) were similar (0.84, 0.85, 0.84, 0.85). Spline regression models did not show
      monotonicity of the dose-response functions at the right end of the RDI
      distribution. Neither the hypoxemia index nor the arousal index was associated
      with carotid plaque or carotid IMT. CONCLUSION: The results of this study suggest
      that crude, positive associations between SDB and subclinical atherosclerosis can
      be attributed to confounding by CVD risk factors.

PMID- 17433331
TI  - Dynamic response of the brain with vasculature: a three-dimensional computational
      study.
AB  - To date, the influence of the vasculature on the dynamic response of the brain
      has not been studied with a complete three-dimensional (3D) finite element head
      model. In this study, short duration rotational (10,000 rad/s(2) with a duration
      of 5 ms) and translational (100G with a duration of 5 ms) acceleration impulses
      were applied to the 3D finite element models to study the dynamic response of the
      brain. The hypothesis of this study was that due to the convoluted organization
      and non-linear material properties of cerebral vasculature, the difference in
      maximum principle strain between models with and without vasculature should be
      minimal. The effects of non-linear material properties and the convoluted
      structure of the vasculature were examined by comparing the results from the 3D
      finite element models. The peak average strain reduction in a model with non
      linear elastic vasculature and a model with linear elastic vasculature compared
      to a model without vasculature was 2% and 5%, respectively, indicating that the
      influence of the vasculature on the dynamic response of the brain is minimal.

PMID- 17433332
TI  - The effects of sloped surfaces on locomotion: backward walking as a perturbation.
AB  - The purpose of this study was to examine lower extremity kinetics and muscle
      activity during backward slope walking to clarify the relationship between joint
      moments and powers and muscle activity patterns observed in forward slope
      walking. Nine healthy volunteers walked backward on an instrumented ramp at three
      grades (-39% (-21 degrees ), 0% (level), +39% (+21 degrees )). EMG activity was
      recorded from major lower extremity muscles. Joint kinetics were obtained from
      kinematic and force platform data. The knee joint moment and power generation
      increased significantly during upslope walking; hip joint moment and power
      absorption increased significantly during downslope walking. When compared to
      data from forward slope walking, these backward walking data suggest that power
      requirements of a task dictate the muscle activity pattern needed to accomplish
      that movement. During downslope walking tasks, power absorption increased and
      changes in muscle activity patterns were directly related to the changes in the
      joint moment patterns. In contrast, during upslope walking tasks, power
      generation increased and changes in the muscle activity were related to the
      changes in the joint moments only at the 'primary' joint; at adjacent joints the
      changes in muscle activity were unrelated to the joint moment pattern. The
      'paradoxical' changes in the muscle activity at the adjacent joints are possibly
      related to the activation of biarticular muscles required by the increased power
      generation at the primary joint. In total, these data suggest that changing power
      requirements at a joint impact the control of muscle activity at that and
      adjacent joints.

PMID- 17433333
TI  - Physical validation of a patient-specific contact finite element model of the
      ankle.
AB  - A validation study was conducted to determine the extent to which computational
      ankle contact finite element (FE) results agreed with experimentally measured
      tibio-talar contact stress. Two cadaver ankles were loaded in separate test
      sessions, during which ankle contact stresses were measured with a high
      resolution (Tekscan) pressure sensor. Corresponding contact FE analyses were
      subsequently performed for comparison. The agreement was good between FE-computed
      and experimentally measured mean (3.2% discrepancy for one ankle, 19.3% for the
      other) and maximum (1.5% and 6.2%) contact stress, as well as for contact area
      (1.7% and 14.9%). There was also excellent agreement between histograms of
      fractional areas of cartilage experiencing specific ranges of contact stress.
      Finally, point-by-point comparisons between the computed and measured contact
      stress distributions over the articular surface showed substantial agreement,
      with correlation coefficients of 90% for one ankle and 86% for the other. In the
      past, general qualitative, but little direct quantitative agreement has been
      demonstrated with articular joint contact FE models. The methods used for this
      validation enable formal comparison of computational and experimental results,
      and open the way for objective statistical measures of regional correlation
      between FE-computed contact stress distributions from comparison articular joint
      surfaces (e.g., those from an intact versus those with residual intra-articular
      fracture incongruity).

PMID- 17433334
TI  - The effect of muscle loading on the kinematics of in vitro glenohumeral
      abduction.
AB  - This in vitro study evaluated the effects of four different muscle-loading ratios
      on active glenohumeral joint abduction. Eight cadaveric shoulders were tested
      using a shoulder simulator designed to reproduce unconstrained abduction of the
      humerus via computer-controlled pneumatic actuation. Forces were applied to
      cables that were sutured to tendons or fixed to bone, to simulate loading of the
      supraspinatus, subscapularis, infraspinatus/teres minor, and anterior, middle,
      and posterior deltoid muscles. Four sets of muscle-loading ratios were employed,
      based on: (1) equal loads, (2) average physiological cross-sectional areas
      (pCSAs), (3) constant values of the product of electromyographic (EMG) data and
      pCSAs, and (4) variable ratios of the EMG and pCSA data which changed as a
      function of abduction angle. The investigator generated passive motions with no
      muscle loads simulated. Repeatability was quantified by five successive trials of
      the passive and simulated active motions. There was improved repeatability in the
      simulated active motions versus passive motions, significant for abduction angles
      less than 40 degrees (p=0.02). No difference was found in the repeatability of
      the four different muscle-loading ratios for simulated active motions (p0.067 for
      all angles). The improved repeatability of active over passive motion suggests
      simulated active motion should be employed for in vitro simulations of shoulder
      motion.

PMID- 17433335
TI  - The compressive material properties of the plantar soft tissue.
AB  - The plantar soft tissue is the primary means of physical interaction between a
      person and the ground during locomotion. Dynamic loads greater than body weight
      are borne across the entire plantar surface during each step. However, most
      testing of these tissues has concentrated on the structural properties of the
      heel pad. The purpose of this study was to determine the material properties of
      the plantar soft tissue from six locations beneath: the great toe (subhallucal),
      the 1st, 3rd and 5th metatarsal heads (submetatarsal), the lateral midfoot
      (lateral submidfoot) and the heel (subcalcaneal). We obtained specimens from
      these locations from 11 young, non-diabetic donors; the tissue was cut into 2 cm
      x 2 cm blocks and the skin was removed. Stress relaxation experiments were
      conducted and the data were fit using the quasi-linear viscoelastic (QLV) theory.
      To determine tissue modulus, energy loss and the effect of test frequency, we
      also conducted displacement controlled triangle waves at five frequencies ranging
      from 0.005 to 10 Hz. The subcalcaneal tissue was found to have an increased
      relaxation time compared to the other areas. The subcalcaneal tissue was also
      found to have an increased modulus and decreased energy loss compared to the
      other areas. Across all areas, the modulus and energy loss increased for the 1
      and 10 Hz tests compared to the other testing frequencies. This study is the
      first to generate material properties for all areas of the plantar soft tissue,
      demonstrating that the subcalcaneal tissue is different than the other plantar
      soft tissue areas. These data will have implications for foot computational
      modeling efforts and potentially for orthotic pressure reduction devices.

PMID- 17433336
TI  - How effective are added constraints in improving TKR kinematics?
AB  - Newer designs of total knee arthroplasty (TKA), through the use of added degrees
      of constraint, attempt to provide a "guided motion" to restore more normal and
      predictable kinematics. Two such design philosophies are the posterior stabilised
      (PS) using a cam-post and the medial pivot (MP) concepts. Knee kinematics of 12
      patients with a PS TKA, 13 subjects with a MP TKA and 10 normal subjects were
      compared. For kinematic assessment, patients underwent fluoroscopic assessment of
      the knee during a step-up exercise and deep knee bend. Fluoroscopic images were
      corrected for distortion and assessed using 3D model fitting to determine
      relative 3D motion, and a 2D method to measure the patellar tendon angle (PTA) as
      function of knee flexion. For the PS design the cam-post mechanism engaged
      between 70 degrees and 100 degrees flexion. Between extension and 50 degrees
      there was forward motion of the contact points. Beyond 60 degrees both condyles
      rolled moved posteriorly. The majority of the external rotation of the femur
      occurred between 50 degrees and 80 degrees . The PTA was lower than normal in
      extension and higher than normal in flexion. The MP exhibited no anterior
      movement throughout the rage of motion. The medial condyle moved minimally. The
      lateral contact point moved posteriorly from extension to flexion. The femur
      rotated externally throughout the range of flexion analysed. The PTA was similar
      to normal from extension to mid flexion and then higher than normal beyond to
      high flexion. The PS design fails to fully restrain paradoxical anterior movement
      and although the cam engages, it does not contribute significantly to overall
      rollback. The MP knee does not show significant anterior movement, the medial
      pivot concept appears to achieve near normal kinematics from extension to 50
      degrees of knee flexion. However, the results show that at high flexion this
      design does not achieve normal knee kinematics.

PMID- 17433337
TI  - Limited rotation of the mobile-bearing in a rotating platform total knee
      prosthesis.
AB  - The hypothesis of this study was that the polyethylene bearing in a rotating
      platform total knee prosthesis shows axial rotation during a step-up motion,
      thereby facilitating the theoretical advantages of mobile-bearing knee
      prostheses. We examined 10 patients with rheumatoid arthritis who had a rotating
      platform total knee arthroplasty (NexGen LPS mobile, Zimmer Inc. Warsaw, USA).
      Fluoroscopic data was collected during a step-up motion six months
      postoperatively. A 3D-2D model fitting technique was used to reconstruct the in
      vivo 3D kinematics. The femoral component showed more axial rotation than the
      polyethylene mobile-bearing insert compared to the tibia during extension. In
      eight knees, the femoral component rotated internally with respect to the tibia
      during extension. In the other two knees the femoral component rotated externally
      with respect to the tibia. In all 10 patients, the femur showed more axial
      rotation than the mobile-bearing insert indicating the femoral component was
      sliding on the polyethylene of the rotating platform during the step-up motion.
      Possible explanations are a too limited conformity between femoral component and
      insert, the anterior located pivot location of the investigated rotating platform
      design, polyethylene on metal impingement and fibrous tissue formation between
      the mobile-bearing insert and the tibial plateau.

PMID- 17433338
TI  - The significance of bone microstructure in mechanotransduction.
AB  - Recent developments in modeling the relationship between bone microstructure and
      mechanotransduction are reviewed. The focus is on the relationship between the
      bone microstructure and the mechanosensation mechanism by which osteocytes sense
      the bone fluid motion propelled by the mechanical loading of the whole bone.

PMID- 17433339
TI  - Preparative separation of isomeric and stereoisomeric dicarboxylic acids by pH
      zone-refining counter-current chromatography.
AB  - This work involves the preparative separation of some isomeric dicarboxylic acids
      using pH-zone-refining counter-current chromatography (CCC), a relatively new
      preparative technique for the separation of ionizable compounds. The paper
      concentrates especially on the separation of a synthetic mixture of closely
      related cis and trans pairs of 1-methyl- and 1,3-dimethyl-1,3
      cyclohexanedicarboxylic acids. The elution sequence of the isomers is discussed
      in terms of their relative acidities (pK(a) values) in solution and gas phase,
      hydrophobicities, and steric configuration. Two possible explanations are
      suggested for the mechanism of separation. They both involve the amount of
      retainer acid used, as it affects the separation and plays a role in the
      chemohydrodynamic equilibrium of the dicarboxylic acids in the column.

PMID- 17433340
TI  - Rapid determination of cyclamate in foods by solid-phase extraction and capillary
      electrophoresis.
AB  - A method for the determination of cyclamate in food was developed using solid
      phase extraction (SPE) and capillary electrophoresis (CE) with indirect
      ultraviolet (UV) detection. A 5-10 g sample in 0.1 mol/L hydrochloric acid was
      homogenized and made up to a volume of 50 mL with 0.1 mol/L hydrochloric acid.
      After the sample was centrifuged, 25 mL of supernatant was loaded into an Oasis
      HLB SPE cartridge. The cartridge was washed with 2 mL of demineralized water
      followed by 2 mL of 50% aqueous methanol, and cyclamate was eluted with 4.5 mL of
      50% aqueous methanol. The eluate was added to a solution of sodium propionate
      (internal standard) for CE analysis. The cyclamate in the eluate was
      electrophoresed on a fused-silica capillary using 1 mmol/L
      hexadecyltrimethylammonium bromide and 10 mmol/L potassium sorbate as a running
      buffer. Detection and reference wavelengths of cyclamate determined with a UV
      detector were 300 and 254 nm, respectively. The calibration curves for cyclamate
      showed good linearity in the range of 2-1000 microg/mL and the limits of
      detection in beverage, fruit in syrup, jam, pickles and confectionary are sample
      dependent and ranged from 5-10 microg/g. The recovery of cyclamate added at a
      level of 200 microg/g to various kinds of foods was 93.3-108.3% and the relative
      standard deviation was less than 4.9% (n=3). A number of commercial samples were
      analyzed using the proposed method. Cyclamate was detected in one waume, two
      pickles, and two sunflower seeds. The quantitative values determined with CE
      correlated to those from high-performance liquid chromatography (HPLC) (the
      detected values of cyclamate in a sunflower seed measured by CE and HPLC were
      3.40 g/kg and 3.51 g/kg, respectively). This analytical method for cyclamate
      using CE is especially suitable for use in the field.

PMID- 17433341
TI  - The docking of chiral epoxides on the Whelk-O1 stationary phase: a molecular
      dynamics study.
AB  - The docking of analytes on the Whelk-O1 chiral stationary phase is explored for
      two chiral epoxides in a hexane solvent. Density functional theory calculations
      are employed to develop flexible models for R/S-styrene oxide (phenyl oxirane)
      and (R,R/S,S)-stilbene oxide (2,3-diphenyl oxirane). Molecular dynamics
      simulations of the racemates in the presence of the Whelk-O1 chiral stationary
      phase reveal the distribution of the enantiomers at the interface. The importance
      of hydrogen bonding and ring-ring interactions is explored along with an
      examination of the major docking arrangements. The interactions between the Whelk
      O1 molecules and the chiral epoxide enantiomers are quite distinct and consistent
      with the experimental elution orders [S.E. Schaus, B.D. Brandes, J.F. Larrow, M.
      Tokunage, K.B. Hansen, A.E. Gould, M.E. Furrow, E.N. Jacobsen, J. Am. Chem. Soc.
      124 (2001) 1307] and separation factors [W.H. Pirkle, C.J. Welch, Tetrahedron:
      Asymm. 5 (1994) 777]. The impact of a polar solvent modifier is examined for R/S
      styrene oxide where selectivity in 80:20 n-hexane:2-propanol is assessed.

PMID- 17433342
TI  - Plasmid purification using non-porous anion-exchange silica fibres.
AB  - A new type of fibre-based anion-exchange material for plasmid purification was
      developed. The basic material consisted of non-porous silica fibres with a mean
      diameter of 1.5 microm and a surface area of 2.4m(2)g(-1). The fibre surface was
      provided with several types of ligands, either by adsorption of polymers
      (chitosan or poly(ethyleneimine)) or by polymerization of amine-containing
      acrylic monomers onto a propyl methacrylate-silanized surface. The resulting
      polymer layers contained primary, tertiary or quaternary amines as ion-exchange
      groups. The packing density could be varied considerably, 9-34% (v/v). The loose
      packing structure provided excellent flow properties suitable for high-speed
      operations. The best overall performance was shown by silica fibres provided with
      tertiary amine polymers, having a plasmid-binding capacity of 0.9 mg ml(-1) (pre
      purified plasmid) and a plasmid recovery of 62% (performance data remained stable
      though several adsorption cycles). The high flow rates possible with the fibre
      material made it especially useful when large volumes of cleared lysate were
      processed. The columns could be operated with retention of their adsorption
      properties at speeds of up to 1800 cm h(-1), equivalent to 0.5 column volumes per
      minute. The binding capacity was found to be lower than anticipated from the
      design of the fibres. Fluorescence imaging showing individual plasmid molecules
      indicated the fibre population to be heterogeneous with respect to plasmid
      adsorption, some fibres displaying poor binding properties. Possible reasons for
      this heterogeneity are discussed.

PMID- 17433343
TI  - Comparison of flavonoid profiles of Agauria salicifolia (Ericaceae) by liquid
      chromatography-UV diode array detection-electrospray ionisation mass
      spectrometry.
AB  - Liquid chromatography (LC) coupled to negative electrospray ionisation (ESI)
      tandem mass spectrometry (MS/MS) was used for the rapid and sensitive
      identification of flavonoid compounds in Agauria salicifolia. The leaf flavonoid
      content in individual of A. salicifolia originating from population with
      contrasted ecogeographical situation and morphological characteristics was found
      to be variable qualitatively and highly variable quantitatively. Identification
      of the compounds was carried out by interpretation of UV, MS and MS/MS spectra.
      Fourteen flavonoids were identified, all of which had not previously been
      reported in Agauria spp. Two flavonol-O-glucuronides were found to differentiate
      the two populations.

PMID- 17433344
TI  - Combined supercritical fluid chromatographic methods for the characterization of
      octadecylsiloxane-bonded stationary phases.
AB  - In this paper, we present a combination of a key-solute test based on retention
      and separation factors of large probe solutes (carotenoid pigments) and a
      quantitative structure-retention relationship analysis based on the retention
      factors of small probe solutes (aromatic compounds) to investigate the different
      chromatographic behavior of octadecylsiloxane-bonded stationary phases of all
      sorts: classical, protected against silanophilic interactions or not, containing
      polar groups (endcapping groups or embedded groups). Varied chemometric methods
      are used to enlighten the differences between the 27 phases tested. The results
      indicate that the two approaches chosen (carotenoid test and solvation parameter
      model) are complementary and provide precise information on the chromatographic
      behavior of ODS phases.

PMID- 17433345
TI  - Pressurized liquid extraction combined with capillary electrophoresis-mass
      spectrometry as an improved methodology for the determination of sulfonamide
      residues in meat.
AB  - A new analytical method, based on capillary electrophoresis and tandem mass
      spectrometry (CE-MS2), is proposed and validated for the identification and
      simultaneous quantification of 12 sulfonamides (SAs) in pork meat. The studied
      SAs include sulfathiazole, sulfadiazine, sulfamethoxypyridazine, sulfaguanidine,
      sulfanilamide, sulfadimethoxyne, sulfapyridine, sulfachloropyridazine,
      sulfisoxazole, sulfasalazine, sulfabenzamide and sulfadimidine. Different
      parameters (i.e. separation buffer, sheath liquid, electrospray conditions) were
      optimized to obtain an adequate CE separation and high MS sensitivity. MS2
      experiments using an ion trap as analyzer, operating in the selected reaction
      monitoring (SRM) mode, were carried out to achieve the required number of
      identification points according to the 2002/657/EC European Decision. For the
      quantification in pork tissue samples, a pressurized liquid extraction (PLE)
      procedure, using hot water as extractant followed by an Oasis HLB cleanup, was
      developed. Linearity (r between 0.996 and 0.997), precision (RSD<14 %) and
      recoveries (from 76 to 98%) were satisfactory. The limits of detection and
      quantification (below 12.5 and 46.5 microg kg(-1), respectively) were in all
      cases lower than the maximum residue limits (MRLs), indicating the potential of
      CE-MS2 for the analysis of SAs, in the food quality and safety control areas.

PMID- 17433346
TI  - Selective method for the analysis of perchlorate in drinking waters at nanogram
      per liter levels, using two-dimensional ion chromatography with suppressed
      conductivity detection.
AB  - The United States Environmental Protection Agency (EPA) collected drinking water
      occurrence data for perchlorate in the Unregulated Contaminant Monitoring
      Regulation (UCMR 1; 2001-2005) using EPA Method 314.0. To address the interest in
      increasing sensitivity and selectivity for the analysis of perchlorate, three new
      methods, EPA Methods 314.1, 331.0 and 332.0, were subsequently published by EPA
      for the analysis of perchlorate in drinking water. In 2006, an automated two
      dimensional ion chromatography (2D-IC) method for measuring perchlorate with
      suppressed conductivity detection was developed. Two-dimensional IC is
      essentially an automated "heart-cutting", column concentration and matrix
      elimination technique. In the first dimension, a large sample volume is injected
      onto a first separation column and the separated matrix ions are diverted to
      waste while the analyte(s) of interest are selectively cut, trapped and
      concentrated in a concentrator column. In the second dimension, the contents from
      the concentrator column are eluted onto a second analytical column for separation
      and quantitation of the analyte(s) of interest. Incorporation of two columns with
      different affinities for the analyte(s) in a single analysis can provide
      comparable selectivity and superior sensitivity to a method using second column
      confirmation in a second separate analysis step. Use of this approach led to the
      development of a new, highly sensitive and selective 2D-IC, suppressed
      conductivity method with a Lowest Concentration Minimum Reporting Level (LCMRL)
      of 55 ng/L for perchlorate in drinking water samples. This new method has
      comparable sensitivity and selectivity and is simpler and more economical than IC
      mass spectrometric (MS) or IC-MS-MS techniques. The method is now being prepared
      for publication as EPA Method 314.2.

PMID- 17433347
TI  - Multi-grams scale purification of xanthanolides from Xanthium macrocarpum.
      Centrifugal partition chromatography versus silica gel chromatography.
AB  - Plants of the Asteraceae family are known as a source of sesquiterpene lactones
      with interesting biological activities. The purification of several xanthanolides
      (xanthathin, 4-epi-xanthanol and 4-epi-isoxanthanol) was realized in one step,
      directly from the crude chloroformic extract of the leaves of X. macrocarpum by
      silica gel chromatography and for the first time by liquid/liquid chromatography
      (counter-current chromatography/centrifugal partition chromatography), using a
      FCPC 5L (Fast centrifugal partition chromatograph, Kromaton Technologies, Angers,
      France). Recovery, purity of xanthathin and solvent consumption were improved
      with the liquid/liquid chromatography compared to solid/liquid chromatography.

PMID- 17433348
TI  - DC conductivity, cationic exchange capacity, and specific surface area related to
      chemical composition of pore lining chlorites.
AB  - Low resistivity in argillaceous sandstone reservoirs may be attributed either to
      the effect of microporosity, or to specific effects due to intrinsic clays'
      conducting properties or to other conducting minerals. In order to distinguish
      these effects, cation exchange capacity, specific surface areas, and dc
      conductivity of various pore lining chlorite-bearing sandstones from different
      hydrocarbon reservoir measurements are investigated. Cation exchange capacity and
      specific surface area are measured on whole rocks as well as on size-separated
      fractions. Both sets of values are low, in agreement with the structural and
      textural observations. The conductivity of these chlorites, measured in air
      conditions and after dehydration, is investigated by means of complex impedance
      spectroscopy on size-separated fractions as a function of temperature and
      compared to that of reference clays. The results show a large influence of
      moisture, applied electric field frequency, and temperature on the electrical
      properties. The magnitude of the dehydrated clays' conductivity is such that its
      influence on the conductivity of argillaceous sandstone is lower than that
      related to the presence of water or brine by several orders of magnitude. The dc
      conductivity and the related activation energy of the dehydrated samples appear
      to be related to the chemical composition of the clays. More specifically, a
      clear correlation occurs with the electrical charges of the clay network, that is
      to say with the location, i.e., tetrahedral or octahedral sites, of the
      substituting trivalent elements.

PMID- 17433349
TI  - Nickel nanoparticles obtained by a modified polyol process: synthesis,
      characterization, and magnetic properties.
AB  - The synthesis of nickel nanoparticles using poly(N-vinilpyrrolidone) (PVP) as
      protective agent was studied. The nanoparticles were prepared in air according to
      a modified polyol route, using nickel chloride as precursor and sodium
      borohydride as reducing agent. Samples with different nickel/PVP ratio were
      obtained. The X-ray diffraction and transmission electron microscopy (TEM)
      measurements indicate the occurrence of face-centered cubic metallic nickel
      nanoparticles with a medium diameter of 3.8 nm and good size dispersion. Fourier
      transformed infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy
      (XPS) data show an effective interaction between the nickel nanoparticles surface
      and the carboxyl oxygen atoms of PVP. Magnetic measurements show single-domain
      nonideal superparamagnetism behavior due to dipolar magnetic coupling between
      particles.

PMID- 17433350
TI  - Deposition efficiency of fractal-like aggregates in fibrous filters calculated
      using Brownian dynamics method.
AB  - Nonspherical particles, such as fractal-like aggregates emitted by diesel
      engines, are commonly met in the ambient air. Some of them are believed to be
      carcinogenic to humans, thus their efficient removal is of crucial practical
      importance. A fibrous filter is the device commonly used for aerosol purification
      but the literature lacks experimental data concerning aggregates filtration.
      Effect of aggregates' parameters (fractal dimension, primary particle radius) as
      well as fiber diameter and air velocity on the filtration efficiency is
      investigated theoretically using the modified Brownian dynamics method. Three
      different expressions for the friction coefficient evaluation for the aggregates
      were examined. The results obtained indicate that structure of an aggregate,
      filter structure and process conditions strongly influence the aggregates
      deposition efficiency, which significantly differs from the values determined for
      mass-equivalent spherical particles. The results determined using the Brownian
      dynamics approach were compared with the values calculated using classical single
      fiber theory and noticeable discrepancy was observed for the most penetrating
      particles, while both approaches agree for the limiting cases of small or large
      particles. Peclet number based on the mobility radius and the interception
      parameter based on the outer radius are the proper criteria to describe
      diffusional and deterministic deposition of aggregates.

PMID- 17433351
TI  - Assessment on the removal of dimethyl phthalate from aqueous phase using a
      hydrophilic hyper-cross-linked polymer resin NDA-702.
AB  - A hydrophilic hyper-cross-linked polymer resin (NDA-702) was synthesized, and the
      adsorption performance of dimethyl phthalate (DMP) on NDA-702 was compared with
      that on the commercial hydrophobic macroporous resin (Amberlite XAD-4) and
      granular activated carbon (AC-750). The kinetic adsorption of DMP onto NDA-702
      and AC-750 is limited mainly by intraparticle diffusion and obeys the pseudo
      second-order rate model, while the uptake on XAD-4 is limited mainly by film
      diffusion and follows the pseudo-first-order rate model. All the associated
      adsorption isotherms are well described by the Freundlich equation, and the
      larger uptake and stronger affinity of NDA-702 than AC-750 and XAD-4 probably
      result from the microporous structure, phenyl rings, and polar groups on NDA-702
      polymer matrix. An interesting observation is that in the aqueous phase all the
      adsorbents spontaneously adsorb DMP driven mainly by enthalpy change, but the
      hydrophilic nature of NDA-702 and AC-750 surfaces results in less entropy change
      compared to hydrophobic XAD-4. Dynamic adsorption studies show that the high
      breakthrough and the total adsorption capacities of NDA-702 are 388 and 559 mg
      per gram dry resin at 313 K. Nearly 100% regeneration efficiency for the resin
      was achieved by methanol at 313 K.

PMID- 17433352
TI  - Preparation of magnetite nanocrystals with surface reactive moieties by one-pot
      reaction.
AB  - By one-pot reaction, biocompatible magnetite nanocrystals with surface reactive
      moieties were prepared through the thermal decomposition of Fe(acac)(3) in 2
      pyrrolidone using alpha,omega-dicarboxyl-terminated poly(ethylene glycol) as
      surface capping molecule. The successful conjugation between the magnetite
      nanocrystals and 9-amino acridine on the one hand demonstrates the existence of
      free carboxylic groups from PEG binding on the particle surface, on the other
      hand may also lead to a new type of magneto-optical materials as well as magneto
      drugs.

PMID- 17433353
TI  - Conductivity stopped-flow study of the kinetics of solutes uptake by colloidal
      particles of synthetic resins.
AB  - The uptake rates of acids (hydrochloric acid, sulfuric acid, perchloric acid and
      acetic acid) by colloidal solid particles (mean diameter 0.35 microm) of DEAE
      (diethylaminoethyl Sephadex) resin was studied by the means of the stopped flow
      technique equipped with a conductivity detection. This original experimental
      approach allows to avoid hydrodynamics perturbations during data acquisition. For
      the sake of comparison NaOH uptake or K(+)/H(+) exchange by sulfonic Dowex resin
      particles experiments have also been performed. As stated in the literature we
      observed that the uptake rate limiting step is the solute diffusion in the
      solution layer surrounding the particles. To fit the experimental conductivity
      versus time curves on the basis of solutes diffusion concepts a simple
      mathematical equation fitting perfectly well the experimental data is proposed.
      The mathematical modeling of kinetic data obtained in non-stationary diffusion
      proposed here can substitute to the empiric pseudo-first- and -second-order
      models often used in environmental research.

PMID- 17433354
TI  - Spectroscopic studies on the interaction between human hemoglobin and CdS quantum
      dots.
AB  - The interaction between human adult hemoglobin (Hb) and bare CdS quantum dots
      (QDs) was investigated by fluorescence, synchronous fluorescence, circular
      dichroism (CD), and Raman spectroscopic techniques under physiological pH 7.43.
      The intrinsic fluorescence of Hb is statically quenched by CdS QDs. The quenching
      obeys the Stern-Volmer equation, with an order of magnitude of binding constant
      (K) of 10(7). The electrostatic adsorption of Hb on the cationic CdS QDs surface
      is energetically favorable (DeltaS(0)=70.22 Jmol(-1)K(-1), DeltaH(0)=-23.11
      kJmol(-1)). The red shift of synchronous fluorescence spectra revealed that the
      microenvironments of tryptophan and tyrosine residues at the alpha(1)beta(2)
      interface of Hb are disturbed by CdS QDs, which are induced from hydrophobic
      cavities to a more exposed or hydrophilic surrounding. The secondary structure of
      the adsorbed Hb has a loose or extended conformation for which the content of
      alpha-helix has decreased from 72.5 to 60.8%. Moreover, Raman spectra results
      indicated that the sulfur atoms of the cysteine residues form direct chemical
      bonds on the surface of the CdS QDs. The binding does not significantly affect
      the spin state of the heme iron, and deoxidation is not expected to take place on
      the coated oxyhemoglobin. The change of orientation of heme vinyl groups was also
      detected.

PMID- 17433355
TI  - Issues of development and plasticity of the auditory system.

PMID- 17433356
TI  - Effects of age and age-related hearing loss on the brain.
AB  - It is well documented that aging adversely affects the ability to perceive time
      varying acoustic cues. Here we review how physiological measures are being used
      to explore the effects of aging (and concomitant hearing loss) on the neural
      representation of temporal cues. Also addressed are the implications of current
      research findings on the rehabilitation of older hearing-impaired adults. LEARNER
      OUTCOMES: (1) Identify one evoked potential that reflects age-related
      physiological changes in the brain. (2) List three contributing factors for why
      older adults have difficult understanding speech in noise. (3) Give an example of
      a top-down approach to auditory rehabilitation.

PMID- 17433358
TI  - A rapid and efficient method for the generation and screening of monoclonal
      antibodies specific for cell surface antigens.
AB  - The generation of monoclonal antibodies (mAb) of desired specificity to cell
      surface antigens can serve as a valuable tool to study protein expression and
      function. However, traditional approaches to mAb generation usually involve large
      scale protein purification and intensive screening, and may not result in mAb
      specificities to the native protein of interest. We describe a simple,
      inexpensive, high-throughput method for the generation and screening of
      hybridomas secreting mAb specific for cell surface receptors. Intact reporter
      cells expressing a CD3zeta-fusion receptor of the protein of interest are plated
      in 96-well arrays of captured, plate-bound hybridoma supernatants. A mAb to the
      protein of interest generates a signal leading to reporter-cell expression of
      beta-galactosidase, and enzyme activity can be screened in a single day using a
      non-radioactive substrate. Importantly, a single cell line can be used for
      immunization, screening, semi-quantitative affinity comparisons, and subsequent
      screening for physiological ligand expression, if the protein of interest is a
      receptor. We describe an application of this approach to generate mAb specific
      for a protein of previously unknown expression and undocumented function.

PMID- 17433357
TI  - Central auditory development: evidence from CAEP measurements in children fit
      with cochlear implants.
AB  - In normal-hearing children the latency of the P1 component of the cortical evoked
      response to sound varies as a function of age and, thus, can be used as a
      biomarker for maturation of central auditory pathways. We assessed P1 latency in
      245 congenitally deaf children fit with cochlear implants following various
      periods of auditory deprivation. If children experience less than 3.5 years of
      auditory deprivation before implantation, P1 latencies fall into the range of
      normal following 3-6 months of electrical stimulation. Children who experience
      greater than 7 years of deprivation, however, generally do not develop normal P1
      latencies even after years of stimulation. Moreover, the waveforms for these
      patients can be markedly abnormal. Cortical reorganization stimulated by
      deprivation is likely to be a significant factor in both variation in the latency
      and morphology of the cortical evoked response to sound for children fit with a
      cochlear implant and variation in the development of oral speech and language
      function. LEARNING OUTCOMES: The reader will be introduced to research using
      cortical evoked responses (CAEPs), positron emission tomography (PET) scans and
      in-depth recording from the auditory cortex of congenitally deaf cats that
      converges on the existence of a sensitive period for the development of central
      auditory pathways in children. The reader will also be provided with two case
      studies that illustrate the use of the P1 response as biomarker for development
      of central auditory pathways. Finally, suggestions for future research will be
      provided.

PMID- 17433359
TI  - In vivo monitoring the fate of Cy5.5-Tat labeled T lymphocytes by quantitative
      near-infrared fluorescence imaging during acute brain inflammation in a rat model
      of experimental autoimmune encephalomyelitis.
AB  - T cells and macrophages directed against myelin proteins orchestrate the
      inflammation process in multiple sclerosis (MS) and experimental autoimmune
      encephalomyelitis (EAE). So far, assessment of macrophages infiltration or
      structural alterations has been achieved by in vivo imaging. In this work, we
      show the infiltration of Cy5.5-labeled T lymphocytes into the brains of EAE rats
      by reflectance near-infrared fluorescence imaging. T lymphocytes were labeled
      with Cy5.5-Tat and administered intravenously to naive or EAE animals. The
      highest fluorescence signal was observed for EAE animals, which received myelin
      activated T cells during the acute phase of the disease. The temporal profile of
      fluorescence in this group paralleled the pattern of neurological impairment
      during the acute phase, the remittance and first relapses of EAE. No disease
      specific fluorescence pattern was observed for EAE animals, which received naive
      T cells. However, uptake of Cy5.5-Tat by scavenger cells (e.g. macrophages)
      following death of labeled T cells in vivo prevents prolonged longitudinal
      studies. Our work demonstrates that Cy5.5-Tat labeling of T cells is suitable for
      in vivo fluorescence imaging of inflammation initiation in the EAE model. This
      approach may particularly be useful for evaluation of novel anti-inflammatory
      therapies.

PMID- 17433360
TI  - Hygroreceptors in the larva of Libellula depressa (Odonata: Libellulidae).
AB  - Ultrastructural and electrophysiological (single-cell recordings) investigations
      were carried out on the coeloconic sensilla borne by the apical antenna of the
      larvae of Libellula depressa (Odonata: Libellulidae). These sensilla appear as
      pegs located in pits. One of them is a compound sensillum constituted of two
      fused pegs in a common pit and the other two are single pegs located in separated
      pits close to each other. Coeloconic sensilla show position and ultrastructural
      details very similar to those described in insect hygroreceptors. The
      electrophysiological recordings on the apical antennae of the last larval instar
      of L. depressa clearly show the presence of moist and dry cells responding
      antagonistically to humidity changes. This study gives the first evidence of
      hygroreceptors in dragonfly larvae and represents the first electrophysiological
      approach to larval sensilla of aquatic insects. The presence of hygroreceptors in
      L. depressa larvae is in agreement with the hygropositive response shown by these
      insects in laboratory and field behavioural experiments.

PMID- 17433361
TI  - Effects of juvenile hormone and 20-hydroxyecdysone on alkaline phosphatase
      activity in Drosophila under normal and heat stress conditions.
AB  - The effect of 20-hydroxyecdysone (20E) and the juvenile hormone (JH) on the
      activity of the alkaline phosphatase (ALP) has been studied in young females of
      wild-type Drosophila virilis and Drosophila melanogaster under normal conditions
      and under heat stress (38 degrees C). Both 20E feeding of the flies and JH
      application led to a substantial rise in ALP activity. ALP activity was also
      measured in young females of a JH-deficient strain of D. melanogaster,
      apterous(56f). A decrease in the enzyme activity was observed in the mutant
      females as compared to wild type. A rise in JH and 20E levels was found not to
      prevent the response of ALP to heat stress, but to change its stress-reactivity.
      Mechanisms of regulation of dopamine (DA) level by gonadotropins in Drosophila
      are discussed.

PMID- 17433362
TI  - Crystal structure of vestitone reductase from alfalfa (Medicago sativa L.).
AB  - Isoflavonoids are commonly found in leguminous plants, where they play important
      roles in plant defense and have significant health benefits for animals and
      humans. Vestitone reductase catalyzes a stereospecific NADPH-dependent reduction
      of (3R)-vestitone in the biosynthesis of the antimicrobial isoflavonoid
      phytoalexin medicarpin. The crystal structure of alfalfa (Medicago sativa L.)
      vestitone reductase has been determined at 1.4 A resolution. The structure
      contains a classic Rossmann fold domain in the N terminus and a small C-terminal
      domain. Sequence and structural analysis showed that vestitone reductase is a
      member of the short-chain dehydrogenase/reductase (SDR) superfamily despite the
      low levels of sequence identity, and the prominent structural differences from
      other SDR enzymes with known structures. The putative binding sites for the co
      factor NADPH and the substrate (3R)-vestitone were defined and located in a large
      cleft formed between the N and C-terminal domains of enzyme. Potential key
      residues for enzyme activity were also identified, including the catalytic triad
      Ser129-Tyr164-Lys168. A molecular docking study showed that (3R)-vestitone, but
      not the (3S) isomer, forms favored interactions with the co-factor and catalytic
      triad, thus providing an explanation for the enzyme's strict substrate stereo
      specificity.

PMID- 17433363
TI  - Sequence determinants of E2-E6AP binding affinity and specificity.
AB  - The conjugation of ubiquitin to substrates requires a series of enzymatic
      reactions consisting of an activating enzyme (E1), conjugating enzymes (E2) and
      ligases (E3). Tagging the appropriate substrate with ubiquitin is achieved by
      specific E2-E3 and E3-substrate interactions. E6AP, a member of the HECT family
      of E3s, has been previously shown to bind and function with the E2s UbcH7 and
      UbcH8. To decipher the sequence determinants of this specificity we have
      developed a quantitative E2-E3 binding assay based on fluorescence polarization
      and used this assay to measure the affinity of wild-type and mutant E2-E6AP
      interactions. Alanine scanning of the E6AP-UbcH7 binding interface identified
      four side-chains on UbcH7 and six side-chains on E6AP that contribute more than 1
      kcal/mol to the binding free energy. Two of the hot spot residues from UbcH7 (K96
      and K100) are conserved in UbcH8 but vary across other E2s. To determine if these
      are key specificity determining residues, we attempted to induce a tighter
      association between the E2 UbcH5b and E6AP by mutating the corresponding
      positions in UbcH5b to lysine residues. Surprisingly, the mutations had little
      effect, but rather a mutation at UbcH7 position 4, which is not at a hot spot on
      the UbcH7-E6AP interface, significantly strengthened UbcH5bs affinity for E6AP.
      This result indicates that E2-E3 binding specificities are a function of both
      favorable interactions that promote binding, and unfavorable interactions that
      prevent binding with unwanted partners.

PMID- 17433364
TI  - Molecular implications of evolutionary differences in CHD double chromodomains.
AB  - Double chromodomains occur in CHD proteins, which are ATP-dependent chromatin
      remodeling factors implicated in RNA polymerase II transcription regulation.
      Biochemical studies suggest important differences in the histone H3 tail binding
      of different CHD chromodomains. In human and Drosophila, CHD1 double
      chromodomains bind lysine 4-methylated histone H3 tail, which is a hallmark of
      transcriptionally active chromatin in all eukaryotes. Here, we present the
      crystal structure of the yeast CHD1 double chromodomains, and pinpoint their
      differences with that of the human CHD1 double chromodomains. The most conserved
      residues in these double chromodomains are the two chromoboxes that orient
      adjacently. Only a subset of CHD chromoboxes can form an aromatic cage for
      methyllysine binding, and methyllysine binding requires correctly oriented
      inserts. These factors preclude yeast CHD1 double chromodomains from interacting
      with the histone H3 tail. Despite great sequence similarity between the human
      CHD1 and CHD2 chromodomains, variation within an insert likely prevents CHD2
      double chromodomains from binding lysine 4-methylated histone H3 tail as
      efficiently as in CHD1. By using the available structural and biochemical data we
      highlight the evolutionary specialization of CHD double chromodomains, and
      provide insights about their targeting capacities.

PMID- 17433365
TI  - Diversity of structural behavior in vertebrate conventional myosins complexed
      with actin.
AB  - Low-resolution three-dimensional structures of acto-myosin subfragment-1 (S1)
      complexes were retrieved from X-ray fiber diffraction patterns, recorded either
      in the presence or absence of ADP. The S1 was obtained from various myosin-II
      isoforms from vertebrates, including rabbit fast-skeletal and cardiac, chicken
      smooth and human non-muscle IIA and IIB species, and was diffused into an array
      of overstretched, skinned skeletal muscle fibers. The S1 attached to the exposed
      actin filaments according to their helical symmetry. Upon addition of ADP, the
      diffraction patterns from acto-S1 showed an increasing magnitude of response in
      the order as listed above, with features of a lateral compression of the whole
      diffraction pattern (indicative of increased radius of the acto-S1 complex) and
      an enhancement of the fifth layer-line reflection. The structure retrieval
      indicates that these changes are mainly due to the swing of the light chain (LC)
      domain in the direction consistent with the cryo-electron microscopic results. In
      the non-muscle isoforms, the swing is large enough to affect the manner of quasi
      crystal packing of the S1-decorated actin filaments and their lattice dimension,
      with a small change in the twist of actin filaments. Variations also exist in the
      behavior of the 50K-cleft, which apparently opens upon addition of ADP to the non
      muscle isoforms but not to other isoforms. The fast-skeletal S1 remains as the
      only isoform that does not clearly exhibit either of the structural changes. The
      results indicate that the "conventional" myosin-II isoforms exhibit a wide
      variety of structural behavior, possibly depending on their functions and/or the
      history of molecular evolution.

PMID- 17433367
TI  - Relationship between memory, attention, and depression in chronic cerebro
      vascular patients.
AB  - Vascular dementia patients show a component of their impairment as emotional. In
      the two studies that we present it was possible to illustrate the characteristics
      of such emotional component. a. The discrepancy between immediate recall and
      delayed recall appears to be very sensitive to anxiety interference when
      immediate recall is lower than delayed. b. The presence of emotional problems
      contributing to memory complaints in VaD patients is not equally distributed
      along the severity of deterioration dimension but can be identified as a specific
      component different from the cognitive one especially in that subgroup of
      patients who present an intermediate level of deterioration.

PMID- 17433366
TI  - Alanine scanning and Fe-BABE probing of the bacteriophage o29 prohead RNA
      connector interaction.
AB  - The DNA packaging motor of the Bacillus subtilis bacteriophage o29 prohead is
      comprised in part of an oligomeric ring of 174 base RNA molecules (pRNA)
      positioned near the N termini of subunits of the dodecameric head-tail connector.
      Deletion and alanine substitution mutants in the connector protein (gp10) N
      terminus were assembled into proheads in Escherichia coli and the particles
      tested for pRNA binding and DNA-gp3 packaging in vitro. The basic amino acid
      residues RKR at positions 3-5 of the gp10 N terminus were central to pRNA binding
      during assembly of an active DNA packaging motor. Conjugation of iron(S)-1-(p
      bromoacetamidobenzyl) ethylenediaminetetraacetate (Fe-BABE) to residue S170C in
      the narrow end of the connector, near the N terminus, permitted hydroxyl radical
      probing of bound [(32)P]pRNA and identified two discrete sites proximal to this
      residue: the C-helix at the junction of the A, C and D helices, and the E helix
      and the CE loop/D loop of the intermolecular base pairing site.

PMID- 17433368
TI  - The pattern of epileptic seizures in rural Tanzania.
AB  - PURPOSE: The study was conducted with the aim of assessing the hospital
      prevalence and aetiology of epileptic seizures with special emphasis on epilepsy
      and febrile convulsions in a rural African hospital. Symptomatic as well as
      unprovoked epileptic seizures have also been accounted for. METHODS: All patients
      admitted over a period of nine months to the Haydom Lutheran Hospital in Northern
      Tanzania were screened for neurological disorders. The present study focuses on
      epileptic seizures only. All patients with convulsions were seen prospectively in
      consecutive order by one of the authors (ASW). RESULTS: Of 8676 admissions 740
      patients (8.5%) were given a neurological diagnosis. The most important
      neurological disorder was epileptic seizures. 272 patients (3.1%) had at least
      one seizure. Febrile convulsions were responsible for 30% (82 patients) of all
      epileptic seizures, followed by epilepsy with 24% (65 patients). Symptomatic
      (provoked) epileptic seizures made up for 27% (72 patients) and were caused by
      cerebral infections, eclampsia, strokes and head injuries. Seizures due to space
      occupying lesions and alcohol withdrawal were also seen. In some cases, the
      reason remained obscure. The inpatient mortality of all seizures was 19%, being
      mainly due to the outcome of symptomatic seizures. The socioeconomic burden of
      hospital treatment of seizures was high corresponding to an average of US $ 20.2,
      paying for an average of 16.9+/-29.0 days in hospital. CONCLUSIONS: Contrary to
      developed countries, the most frequent neurological disorder amongst hospital
      inpatients was seizures. Febrile convulsions and epilepsy were major causes.

PMID- 17433369
TI  - Prediction of membrane protein types from sequences and position-specific scoring
      matrices.
AB  - Membrane protein plays an important role in some biochemical process such as
      signal transduction, transmembrane transport, etc. Membrane proteins are usually
      classified into five types [Chou, K.C., Elrod, D.W., 1999. Prediction of membrane
      protein types and subcellular locations. Proteins: Struct. Funct. Genet. 34, 137
      153] or six types [Chou, K.C., Cai, Y.D., 2005. J. Chem. Inf. Modelling 45, 407
      413]. Designing in silico methods to identify and classify membrane protein can
      help us understand the structure and function of unknown proteins. This paper
      introduces an integrative approach, IAMPC, to classify membrane proteins based on
      protein sequences and protein profiles. These modules extract the amino acid
      composition of the whole profiles, the amino acid composition of N-terminal and C
      terminal profiles, the amino acid composition of profile segments and the
      dipeptide composition of the whole profiles. In the computational experiment, the
      overall accuracy of the proposed approach is comparable with the functional
      domain-based method. In addition, the performance of the proposed approach is
      complementary to the functional-domain-based method for different membrane
      protein types.

PMID- 17433370
TI  - Propagation of local interactions create global gap structure and dynamics in a
      tropical rainforest.
AB  - Gap dynamics in tropical forests are of interest because an understanding of them
      can help to predict canopy structure and biodiversity. We present a simple
      cellular automaton model that is capable of capturing many of the trends seen in
      the canopy gap pattern of a complex tropical rainforest on the Barro Colorado
      Island (BCI) using a single set of model parameters. We fit the global and local
      densities, the cluster size distributions, and two correlation functions, for
      gaps, gap formations, and gap closures determined from a spatial map of the
      forest (1983-1984). To the best of our knowledge, this is the first report that
      the cluster size distributions of gap formations and closures in the BCI are both
      power laws. An important element in the model is that when a transition from gap
      to non-gap (closure), or vice versa (formation), occurs, this transition is
      allowed to expand into adjacent cells in order to make different cluster sizes of
      transitions. Model results are in excellent agreement with reported field data.
      The propagation of local interactions is necessary in order to obtain the complex
      dynamics of the gap pattern. We also establish a connection between the global
      and local densities via the neighborhood-dependent transition rates and the
      effective global transition rates.

PMID- 17433371
TI  - The proteinase inhibitor camostat mesilate suppresses pancreatic pain in rodents.
AB  - Camostat mesilate, an orally available proteinase inhibitor, is clinically used
      for treatment of pancreatitis. Given recent evidence that pancreatic proteinases
      including trypsin and/or proteinase-activated receptor-2 (PAR2) might be involved
      in pancreatic pain, we examined if camostat mesilate could suppress spinal Fos
      expression, a marker for neuronal activation, following specific application of
      trypsin to the pancreas, and pancreatitis-related referred allodynia. Trypsin,
      administered into the pancreatic duct, caused delayed expression of Fos proteins
      in the superficial layer of the bilateral T8 and T9 spinal dorsal horns in rats.
      The trypsin-induced spinal Fos expression was completely abolished by oral pre
      administration of camostat mesilate at 300 mg/kg. After hourly repeated (6 times
      in total) administration of caerulein, mice showed typical symptoms of
      pancreatitis, accompanied by mechanical allodynia in the upper abdomen (i.e.,
      referred hyperalgesia/allodynia), as assessed by use of von Frey filaments.
      Camostat mesilate at 100-300 mg/kg, given orally twice before the 1st and 4th
      doses of caerulein, abolished the pancreatitis-related abdominal allodynia, while
      it partially prevented the inflammatory signs. The same doses of camostat
      mesilate, when administered once after the final dose of caerulein, also revealed
      significant anti-allodynic effect. These data suggest that camostat mesilate
      prevents and/or depresses pancreatitis-induced pain and/or referred
      hyperalgesia/allodynia, in which proteinases including trypsin would play a
      critical role.

PMID- 17433372
TI  - Effects of chemical dispersants and mineral fines on crude oil dispersion in a
      wave tank under breaking waves.
AB  - The interaction of chemical dispersants and suspended sediments with crude oil
      influences the fate and transport of oil spills in coastal waters. A wave tank
      study was conducted to investigate the effects of chemical dispersants and
      mineral fines on the dispersion of oil and the formation of oil-mineral
      aggregates (OMAs) in natural seawater. Results of ultraviolet spectrofluorometry
      and gas chromatography flame ionized detection analysis indicated that
      dispersants and mineral fines, alone and in combination, enhanced the dispersion
      of oil into the water column. Measurements taken with a laser in situ scattering
      and transmissometer (LISST-100X) showed that the presence of mineral fines
      increased the total concentration of the suspended particles from 4 to 10microl
      l(-1), whereas the presence of dispersants decreased the particle size (mass mean
      diameter) of OMAs from 50 to 10microm. Observation with an epifluorescence
      microscope indicated that the presence of dispersants, mineral fines, or both in
      combination significantly increased the number of particles dispersed into the
      water.

PMID- 17433373
TI  - Heavy metal contamination in western Xiamen Bay sediments and its vicinity,
      China.
AB  - Concentrations of selected heavy metals (Cu, Pb, Zn, Cd, Cr, Ni and Fe) in
      surface sediments from nine sites in western Xiamen Bay and its vicinity were
      studied in order to understand current metal contamination due to urbanization
      and economic development in Xiamen, China. The sediment samples were collected in
      December 2004 and July 2005 respectively in order to examine temporal variations.
      In this study, we found that heavy metal concentrations in surface sediments
      sampled in the western Xiamen Bay and adjacent Maluan Bay and Yuandang Lagoon
      varied from 19 to 97mg kg(-1) for Cu, 45 to 60mg kg(-1) for Pb, 65 to 223mg kg(
      1) for Zn, 0.11 to 1.01mg kg(-1) for Cd, 37 to 134mg kg(-1) for Cr, 25 to 65mg
      kg(-1) for Ni and 3.08 to 4.81% for Fe. Although all metal concentrations in
      sediments meets Chinese National Standard Criteria for Marine Sediment Quality,
      both metal enrichment factors (EF) and geoaccumulation index (I(geo)) show that
      Pb contamination exists in the entire study area and contamination of other
      metals are also present in some locations depending on the sources, of which
      sewage outlets and commercial ports are the main sources of contaminants to the
      area. This study shows that using the sediment quality standard criteria only to
      assess sediments cannot properly reflect sediment contamination. A multiple
      approaches should be applied for the sediment quality assessment.

PMID- 17433374
TI  - The role of health care workers and antiviral drugs in the control of pandemic
      influenza.
AB  - Until a vaccine against the new strain becomes available, the response to newly
      emerged pandemic influenza will consist of the use of antiviral drugs and
      measures that limit exposure to infectious individuals. These first-line defence
      measures include isolating cases upon diagnosis, reducing close contacts, the use
      of personal protective equipment and hygiene, and using antiviral drugs for
      treatment and prophylaxis. There are significant 'costs' associated with control
      measures, so to justify such interventions it is important to assess their
      potential to reduce transmission. In this paper, we determine the effect that a
      number of different antiviral interventions have on the reproduction number of
      infectives and the probability that an imported infection fades out, and
      determine parameter scenarios for which these interventions are able to eliminate
      an emerging pandemic of influenza. We also assess the role that health care
      workers play in transmission and the extent to which providing them with
      antiviral prophylaxis and personal protective equipment modifies this role. Our
      results indicate that this class requires protection to avoid a greatly
      disproportionate contribution to early infective numbers, and for the maintenance
      of a stable health care system. Further, we show that the role children play in
      increasing transmission is moderate, in spite of closer mixing with other
      children.

PMID- 17433375
TI  - Genetic and molecular mechanisms of chemical atherogenesis.
AB  - Injury to the cellular components of the vascular wall and blood by endogenous
      and exogenous chemicals has been associated with atherosclerosis in humans and
      experimental systems. The genetic and molecular mechanisms responsible for
      initiation and promotion of atherosclerotic changes include modulation of
      extracellular matrix-integrin axis, genes involved in the regulation of growth
      and differentiation and possibly, genomic stability. This review summarizes
      seminal studies over the past 20 years that shed light on critical gene-gene and
      gene-environment interactions mediating the atherogenic response to chemical
      injury.

PMID- 17433376
TI  - Functional alterations of nicotinic neurotransmission in dopamine transporter
      knock-out mice.
AB  - Mice lacking the dopamine (DA) transporter (DAT) gene exhibit a phenotype
      reminiscent of schizophrenia and attention deficit hyperactivity disorder (ADHD),
      including hyperDAergia, hyperactivity and deficits in cognitive performance,
      which are alleviated by antipsychotic agents. Numerous studies suggest a
      dysfunction of nicotinic neurotransmission in schizophrenia and show increased
      tobacco intake in schizophrenic and ADHD patients, possibly as a self-medication.
      Thus, we examined the potential alteration of nicotinic neurotransmission in DAT
      knock-out (KO) mice. We showed that constitutively hyperDAergic DAT KO mice
      exhibited modifications in nicotinic receptor density in an area- and subtype
      dependent manner. In some DAergic areas, the small decrease in the beta2*
      nicotinic subunit (nAChR) density contrasted with the higher decrease and
      increase in the alpha6* and alpha7 nAChR densities, respectively. Mutant mice
      were hypersensitive to the stimulant locomotor effects of nicotine at low doses,
      probably due to enhanced nicotine-induced extracellular DA level. They also
      showed hypersensitivity to the hypolocomotion induced by nicotine. In contrast,
      no hypersensitivity was observed for other nicotine-induced behavioral effects,
      such as anxiety or motor activity in the elevated plus maze. Co-administration of
      nicotinic agonists at sub-active doses elicited opposite locomotor effects in
      wild-type and DAT KO mice, as reported previously for methylphenidate.
      Interestingly, such a co-administration of nicotinic agonists induced synergistic
      hypolocomotion in DAT KO mice. These findings show that a targeted increase of DA
      tone can be responsible for significant adaptations of the cholinergic/nicotinic
      neurotransmission. This study may provide potential leads for the use of nicotine
      or combined nicotinic agonists for the therapy of psychiatric disorders.

PMID- 17433377
TI  - Synergistic requirements for the induction of dopaminergic D1/D5-receptor
      mediated LTP in hippocampal slices of rat CA1 in vitro.
AB  - Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of
      memory and its cellular model, i.e. hippocampal long-term potentiation (LTP) in
      CA1. D1/D5-receptor function is required for the induction of the protein
      synthesis-dependent maintenance of CA1-LTP (late-LTP) by activating the cAMP/PKA
      pathway. In earlier studies we had reported a synergistic interaction of D1/D5
      receptor function and N-methyl-D-aspartate (NMDA)-receptors (Frey, 2001, Long
      lasting hippocampal plasticity: cellular model for memory consolidation? In:
      Richter, D. (Ed.), Cell Polarity and Subcellular RNA Localization. Springer
      Verlag, Berlin-Heidelberg, pp. 27-40). Interestingly, the short-term application
      of D1/D5-receptor agonists (SKF38393 or 6-bromo-APB, 50 microM) can induce a slow
      onset potentiation. This D1/D5-agonist-induced delayed-onset potentiation (D1/D5
      LTP) resembles late-LTP, i.e. it is dependent on protein synthesis in the CA1 of
      rat hippocampal slices in vitro. The question arises as to whether D1/D5-LTP also
      requires glutamatergic stimulation, i.e. NMDA-receptor activation. We provide
      first evidence that a synergistic role of D1/D5- as well as NMDA-receptor
      function is required in mediating processes relevant for the maintenance of this
      protein synthesis-dependent potentiation.

PMID- 17433379
TI  - Top-down and bottom-up effects in pure alexia: evidence from eye movements.
AB  - The eye movements of a patient with pure alexia, GJ, were recorded as he read
      sentences in order to explore the roles of top-down and bottom-up information
      during letter-by-letter reading. Specifically, the effects of word frequency and
      word predictability were examined. Additional analyses examined the interaction
      of these effects with the lower level influences of word length and letter
      confusability. The results indicate that GJ is sensitive to all four of these
      variables in sentence reading. These findings support an interactive account of
      reading where letter-by-letter readers use both bottom-up and top-down
      information to decode words. Due to the disrupted bottom-up processes caused by
      damage to the Visual Word Form Area or the input connections to it, pure alexic
      patients rely more heavily on intact top-down information in reading.

PMID- 17433380
TI  - Neural correlates of naming newly learned objects in MCI.
AB  - Our objective was to study the neural correlates of naming of newly learned
      unfamiliar objects in subjects with mild cognitive impairment (MCI) and in age
      matched controls, by using positron emission tomography (PET). Prior to the PET
      scanning, each subject underwent a 4-day long training period in which 40 names
      of rare unfamiliar objects were taught. The stimuli consisted of five categories:
      unfamiliar objects for which both the name and the definition (=semantic support)
      were given during training, unfamiliar objects with only the name given,
      unfamiliar objects with no information given, familiar objects and visual noise
      patterns. The unfamiliar objects mainly represented ancient domestic tools
      unknown to modern-day people. When naming newly learned objects trained without
      semantic support, the MCI group showed increased activation in the anterior
      cingulate when compared with the controls. Our results suggest that the naming of
      newly learned objects posed additional executive and attentional demands on the
      patients.

PMID- 17433378
TI  - Dissociation in performance of children with ADHD and high-functioning autism on
      a task of sustained attention.
AB  - Attention deficit hyperactivity disorder (ADHD) and autism are two
      neurodevelopmental disorders associated with prominent executive dysfunction,
      which may be underpinned by disruption within fronto-striatal and fronto-parietal
      circuits. We probed executive function in these disorders using a sustained
      attention task with a validated brain-behaviour basis. Twenty-three children with
      ADHD, 21 children with high-functioning autism (HFA) and 18 control children were
      tested on the Sustained Attention to Response Task (SART). In a fixed sequence
      version of the task, children were required to withhold their response to a
      predictably occurring no-go target (3) in a 1-9 digit sequence; in the random
      version the sequence was unpredictable. The ADHD group showed clear deficits in
      response inhibition and sustained attention, through higher errors of commission
      and omission on both SART versions. The HFA group showed no sustained attention
      deficits, through a normal number of omission errors on both SART versions. The
      HFA group showed dissociation in response inhibition performance, as indexed by
      commission errors. On the Fixed SART, a normal number of errors was made, however
      when the stimuli were randomised, the HFA group made as many commission errors as
      the ADHD group. Greater slow-frequency variability in response time and a slowing
      in mean response time by the ADHD group suggested impaired arousal processes. The
      ADHD group showed greater fast-frequency variability in response time, indicative
      of impaired top-down control, relative to the HFA and control groups. These data
      imply involvement of fronto-parietal attentional networks and sub-cortical
      arousal systems in the pathology of ADHD and prefrontal cortex dysfunction in
      children with HFA.

PMID- 17433381
TI  - Spontaneous eyeblink rate predicts the strength of visuomotor binding.
AB  - The primate cortex represents the external world in a distributed way, which
      requires for a mechanism that integrates the features of a processed event.
      Animal and patients studies suggest that feature binding in the visual cortex is
      under muscarinic-cholinergic control, whereas visuomotor integration is driven by
      the dopaminergic system. Consistent with this picture, we present evidence that
      the binding of visual and action features is modulated by spontaneous eyeblink
      rate (EBR), which is a functional marker of central dopaminergic function.
      Remarkably, the impact of EBR was restricted to the task-relevant visuomotor
      binding, suggesting that dopamine increased the maintenance of task-relevant
      information.

PMID- 17433382
TI  - Role of the medial temporal lobes in relational memory: neuropsychological
      evidence from a cued recognition paradigm.
AB  - In this study, we examined the role of the hippocampus in relational memory by
      comparing item recognition performance in amnesic patients with medial temporal
      lobe (MTL) damage and their matched controls. Specifically, we investigated the
      contribution of associative memory to item recognition using a cued recognition
      paradigm. Control subjects studied cue-target pairs once, whereas amnesic
      patients studied cue-target pairs six times. Following study, subjects made
      recognition judgments about targets that were presented either alone (no cue),
      with the originally presented cue (same cue), or with a cue that had been
      presented with a different target (recombined cue). Controls had higher
      recognition scores in the same cue than in the recombined cue condition,
      indicating that they benefited from the associative information provided by the
      same cue. By contrast, amnesic patients did not. This was true even for a
      subgroup of patients whose recognition performance in the no cue condition was
      matched to that of the controls. These data provide further support for the idea
      that the hippocampus plays a critical role in relational memory, even when
      associative information need not be retrieved intentionally.

PMID- 17433383
TI  - Visual hallucinations during spontaneous and training-induced visual field
      recovery.
AB  - Visual hallucinations after post-geniculate visual system lesions were shown to
      be associated with spontaneous recovery of visual functions. We investigated the
      occurrence of hallucinations during spontaneous recovery and additionally tested
      whether hallucinations were re-instated in a phase of vision restoration therapy
      (VRT). Nineteen patients with post-geniculate lesions and homonymous visual loss
      participated in a prospective study, and 121 patients with various lesions were
      included in a retrospective study using a questionnaire including verbal
      descriptions as well as drawings of hallucinations experienced by the patients.
      In both samples, visual-field size was determined before and after 6 months of
      VRT. Many patients in both groups experienced post-lesion hallucinations (mostly
      colors, objects, motion) which subsided after spontaneous recovery of visual
      functions (increase of visual field size, recovery of more complex visual
      function) was ended. Hallucinations re-emerged during training. However, the
      majority of patients reported simple, unformed visual hallucinations (uncolored
      phosphenes, spots, flashes), especially when visual field recovery was most
      intense. Hallucinations were mainly found in patients with large shifts of the
      visual field border. They occurred in blind areas, particularly in areas of
      residual vision where recovery was predominantly observed. Hallucinations may
      reflect functional recovery in partially lesioned brain areas. While the
      colored/formed hallucinations during spontaneous recovery may represent non
      specific activation of higher visual areas, the simple, unformed training-related
      hallucinations may indicate recovery in the primary visual cortex during
      treatment. Hallucinations should not generally be discarded as pathological or
      unimportant symptoms, but they may be functional indicators of visual system
      plasticity.

PMID- 17433384
TI  - Bilingual language lateralization: a meta-analytic tale of two hemispheres.
AB  - Two meta-analyses of 66 behavioral studies examined variables influencing
      functional cerebral lateralization of each language of brain-intact bilingual
      adults. Functional lateralization was found to be primarily influenced by age of
      onset of bilingualism: bilinguals who acquired both languages by 6 years of age
      showed bilateral hemispheric involvement for both languages, whereas those who
      acquired their second language after age 6 showed left hemisphere dominance for
      both languages. Moreover, among late bilinguals, left hemisphere involvement was
      found to be greater for those less proficient in their second language, those
      whose second language was English, and for studies involving dichotic listening
      paradigms; early bilinguals instead showed bilateral involvement in every
      condition. Implications of the observed differences in lateralization between
      early and late bilinguals are explored for existing theories of bilingualism and
      for neurocognitive models of brain functional organization of language.

PMID- 17433385
TI  - Accelerated binocular rivalry with anxious personality.
AB  - When dissimilar figures are presented to the two eyes individually, perception
      alternates spontaneously between each monocular view. This phenomenon, designated
      binocular rivalry, has been used by many scientists as a tool for investigating
      visual awareness. Some recent studies have suggested involvement of serotonergic
      neural systems in this phenomenon. We explored the relationship between binocular
      rivalry and anxiety, a state thought to be associated with serotonergic neural
      activity. Perceptual alternation rate in dominance of binocular rivalry were
      compared between normal volunteers with high and low general anxiety as measured
      using the harm avoidance (HA) scale of the Tridimensional Personality
      Questionnaire. Perceptual alternation rate and rhythmicity in the high-HA group
      was significantly greater than that in the low-HA group. The perceptual
      alternation rate in binocular rivalry was accelerated in anxious subjects,
      suggesting that binocular rivalry and anxiety may share some common serotonergic
      neural substrates.

PMID- 17433386
TI  - Plasma dopamine and noradrenaline variations in response to stress.
AB  - Dopamine (DA) the precursor of noradrenaline (NA) has been shown to have many
      functions such as its influence on endorphins activity and its association with
      hedonic impact, anxiety and depression. However with regard to the sympathetic
      nervous system activity, the role of DA has merely been considered as being the
      precursor of NA. We have shown in a previous study a positive correlation between
      the resting plasma level of NA and those found during exposure to a physical
      stress. No explanation was proposed to explain this finding. Enhanced sympathetic
      nervous system activity has been shown to increase the secretion of NA as well as
      DA. It is not known however if the secretion of DA during exposure to stress
      parallels that of NA. What are the interactions between the two amines and also
      between values at rest and during exposure to stress? For that reason a test was
      used which consisted of blowing cold wind (4 degrees C at 60 km/h) on the face of
      a group of subjects and measuring plasma concentration of the two amines before,
      during and after the test. For a given individual, the increase of either plasma
      NA or DA in response to the cold wind stress parallels the resting plasma
      concentrations of these two amines respectively. Low level of one amine at rest
      coincides with low increase during the stress. Furthermore the results have shown
      that when the plasma level of either one of these two amines is high in response
      to stress, the values of the other amine are small; both amines are not high or
      low at the same time. The literature suggests that dopamine beta hydroxylase
      (DBH), the enzyme which catalyzes the synthesis of NA from DA, may provide an
      explanation to our findings. Lower DBH activity of this enzyme would result in a
      lower NA and a greater DA storage and secretion. Further investigation is needed
      to verify this possibility.

PMID- 17433388
TI  - Origin and development of the UK Voluntary Register for Public Health
      Specialists.
AB  - This paper describes the milestones, challenges and achievements in establishing
      the UK Voluntary Register for Public Health Specialists (UKVRPHS), which was
      launched in 2003. Developments in the UKVRPHS since 2003 are described in the
      context of the continuing development of the UK multidisciplinary public health
      workforce as a whole.

PMID- 17433387
TI  - Acute paternal alcohol use affects offspring development and adult behavior.
AB  - Swiss Webster pups were fathered by sires given either an acute dose of alcohol
      (alcohol-sired) or saline (saline-sired) 12-24 h before mating. The same sires
      were used to father both groups of pups. Alcohol-sired pups were significantly
      lighter at birth and for the following three weeks than were saline-sired pups.
      Significantly more pups were fathered by saline-exposed sires, and dams carrying
      those pups had significantly longer gestations than those carrying pups of
      alcohol-using sires. More runts were born to the alcohol-sired group, and more
      pups in that group died over the next three weeks than in the saline-sired group.
      Significantly more pups in the saline-sired group achieved such developmental
      milestones as surface righting, clinging, the tail-pull reflex, rotation, linear
      movement and climbing an inclined surface earlier than did alcohol-sired pups. As
      adults, animals from the alcohol-sired group showed significantly less risk
      assessment behavior and longer latencies to such behaviors as stretched
      attention, flatback, freezing and defensive burying than did the saline-sired
      animals. Alcohol-sired animals contacted the stimulus object in the risk
      assessment test significantly sooner and more often than did the saline-sired
      group. In tests of aggression, alcohol-sired male offspring showed more frequent
      aggressive behaviors such as on-top, lateral attacks and jump-attacks, and
      significantly fewer defensive/fearful behaviors such as piloerection, tail
      rattling and jump-escape. This pattern of results suggests that exposure of the
      sire to one acute dose of alcohol before insemination caused some early
      developmental delays and that alcohol-sired animals are less fearful and more
      aggressive as adults than saline-sired animals.

PMID- 17433389
TI  - Acute respiratory distress syndrome in Plasmodium vivax malaria: case report and
      review of the literature.
AB  - Plasmodium vivax infection can cause acute respiratory distress syndrome (ARDS).
      This complication of P. vivax infection is being increasingly recognised and was
      life threatening in a traveller returning from Gujarat, India. Nineteen other
      published cases of P. vivax with respiratory symptoms are also reviewed and
      confirm that ARDS was the underlying complication in most cases. Plasmodium vivax
      associated ARDS is a clinically recognisable condition whose underlying
      pathophysiology is likely to reflect processes that are independent of parasite
      sequestration in the pulmonary microvasculature.

PMID- 17433390
TI  - Serological and blood culture investigations of Nepalese fever patients.
AB  - Serological testing of paired (i.e. admission and convalescent) sera from 103
      fever patients in Kathmandu, Nepal, was performed to estimate the prevalence
      rates of scrub typhus, murine typhus, Leptospira and dengue virus antibodies and
      to determine their role in the cause of active infections. Blood cultures from 15
      patients grew Salmonella enterica serovar Typhi, 8 grew S. Paratyphi A and 6 grew
      other bacteria. Diagnostic antibody levels were detected against murine typhus
      (27/103; 26%), scrub typhus (23/103; 22%), Leptospira (10/103; 10%) and dengue
      virus (8/103; 8%). Nineteen patients (18%) had diagnostically raised antibodies
      to more than one infectious agent. Seven S. Typhi (7/15; 47%) and two S.
      Paratyphi A (2/8; 25%) patients had significant scrub typhus, murine typhus,
      Leptospira or dengue virus IgM antibody titres. This study confirms the presence
      of leptospiral, rickettsial and dengue infections in Kathmandu as well as
      evidence for mixed infections with S. Typhi and Orientia tsutsugamushi or
      Rickettsia typhi. These infections should be kept in mind when considering the
      differential diagnoses of fever and empirical treatment options in Nepal. Many
      patients demonstrated static IgM antibody results between paired serum
      collections, suggesting recent rather than acutely active infections.

PMID- 17433391
TI  - African Programme for Onchocerciasis Control (APOC): sociological study in three
      foci of central Africa before the implementation of treatments with ivermectin
      (Mectizan).
AB  - The African Programme for Onchocerciasis Control (APOC) has put in place a study
      to assess the long-term impact of the community-directed treatments with
      ivermectin on various clinical and entomological indicators of onchocerciasis. As
      the results obtained would depend on community participation in the treatments,
      surveys were also conducted at the study sites to assess the people's knowledge,
      attitudes and practices regarding onchocerciasis and its treatment. This article
      presents the anthropological observations made before the implementation of the
      treatments in three sites: one in the Central African Republic, and two in the
      Democratic Republic of Congo. The information collected shows that the
      populations have a relatively poor knowledge of the manifestations and mode of
      transmission of onchocerciasis. The communities' attitudes towards those
      individuals afflicted with the disease vary from one site to another. Regarding
      treatment, the populations use both traditional and 'modern' treatments, but the
      beneficial effects of ivermectin are not well known. The differences recorded
      between the sites surveyed demonstrate that the messages to be delivered to the
      populations before the distributions should take into account the local
      epidemiological and socio-anthropological context.

PMID- 17433392
TI  - Dispersal delays, predator-prey stability, and the paradox of enrichment.
AB  - It takes time for individuals to move from place to place. This travel time can
      be incorporated into metapopulation models via a delay in the interpatch
      migration term. Such a term has been shown to stabilize the positive equilibrium
      of the classical Lotka-Volterra predator-prey system with one species (either the
      predator or the prey) dispersing. We study a more realistic, Rosenzweig
      MacArthur, model that includes a carrying capacity for the prey, and saturating
      functional response for the predator. We show that dispersal delays can stabilize
      the predator-prey equilibrium point despite the presence of a Type II functional
      response that is known to be destabilizing. We also show that dispersal delays
      reduce the amplitude of oscillations when the equilibrium is unstable, and
      therefore may help resolve the paradox of enrichment.

PMID- 17433393
TI  - A review of the epidemiologic literature on the role of environmental arsenic
      exposure and cardiovascular diseases.
AB  - Cardiovascular disease is the leading cause of mortality worldwide. Arsenic is a
      ubiquitous metalloid in the crust of the earth. Chronic arsenic poisoning is
      becoming an emerging epidemic in Asia. Epidemiological studies have shown that
      chronic arsenic poisoning through ingestion of arsenic-contaminated water is
      associated with various cardiovascular diseases in dose-response relationships.
      These cardiovascular disorders include carotid atherosclerosis detected by
      ultrasonography, impaired microcirculation, prolonged QT interval and increased
      QT dispersion in electrocardiography, and clinical outcomes such as hypertension,
      blackfoot disease (a unique peripheral vascular disease endemic in southwestern
      Taiwan), coronary artery disease and cerebral infarction. Chronic arsenic
      poisoning is an independent risk factor for cardiovascular disease. The adverse
      cardiovascular effects of long-term arsenic exposure may be persistent and/or
      irreversible. Arsenic-induced cardiovascular diseases in human population may
      result from the interaction among genetic, environment and nutritional factors.
      The major adverse cardiovascular effect of chronic arsenic poisoning has been
      established qualitatively and quantitatively in the high arsenic exposure areas,
      but the low-dose effect of arsenic on cardiovascular diseases remains to be
      explored. Cardiovascular death is the major cause of mortality worldwide, and a
      small increased risk may imply a large quantity of excess mortality.

PMID- 17433395
TI  - Further studies on pumiliotoxin 251D and hydroquinone content of the skin
      secretion of Melanophryniscus species (Anura, Bufonidae) from Uruguay.
AB  - In whole animal ethanolic extracts from adult specimens of Melanophryniscus
      atroluteus (27 specimens) and M. devincenzii (16 specimens) as well as of two egg
      clutches and four tadpole samples from the latter species, the major alkaloid
      pumiliotoxin (PTX) 251D and hydroquinone were assayed quantitatively by gas
      chromatography/mass spectrometry. All toad extracts contained high concentrations
      of PTX 251D and hydroquinone and exhibited considerable variation in the content
      of these compounds among individual specimens. The extracts of the eggs and
      tadpoles were entirely free of alkaloids as well as hydroquinone, pointing to a
      dietary origin of these compounds.

PMID- 17433396
TI  - Curcumin-induced genotoxicity and antigenotoxicity in HepG2 cells.
AB  - Curcumin, a polyphenolic yellow pigment found in turmeric, is commonly used as a
      coloring agent in foods, drugs, and cosmetics. In our previous study, we found
      that low levels of curcumin did not increase the reactive oxygen species (ROS)
      formation and caused no damage to DNA in human hepatoma G2 (HepG2) cells, but at
      high doses, curcumin imposed oxidative stress and damaged DNA. In the present
      study, we are determined to investigate the genotoxic and antigenotoxic effects
      of curcumin using HepG2 cell line, a relevant in vitro model to detect the
      cytoprotective, antigenotoxic, and cogenotoxic agents. The results of
      micronucleus (MN) assays showed that, on one hand, curcumin at the high tested
      concentrations (8 and 16 microg/ml) displayed a small but significant increase in
      the frequency of MN, and on the other hand, it was observed that the low tested
      concentration (2 microg/ml) significantly reduced the MN formation induced by the
      chemotherapeutic agent cyclophosphamide. The present results indicate that
      curcumin shows both genotoxicity and antigenotoxicity depending on its
      concentration.

PMID- 17433394
TI  - Cigarette smoke toxicants as substrates and inhibitors for human cytosolic SULTs.
AB  - The current study was designed to examine the role of sulfation in the metabolism
      of cigarette smoke toxicants and clarify whether these toxicants, by serving as
      substrates for the cytosolic sulfotransferases (SULTs), may interfere with the
      sulfation of key endogenous compounds. By metabolic labeling, [(35)S]sulfated
      species were found to be generated and released into the media of HepG2 human
      hepatoma cells and primary human lung endothelial cells labeled with
      [(35)S]sulfate in the presence of cigarette smoke extract (CSE). Concomitantly,
      several [(35)S]sulfated metabolites observed in the medium in the absence of CSE
      either decreased or disappeared. Eleven previously prepared human cytosolic SULTs
      were tested for sulfating activity with CSE and known cigarette smoke toxicants
      as substrates. Activity data revealed SULT1A1, SULT1A2, SULT1A3, and SULT1C#2 as
      major enzymes responsible for their sulfation. To examine their inhibitory
      effects on the sulfation of 17beta-estradiol by SULT1A1, enzymatic assays were
      performed in the presence of three representative toxicant compounds, namely N
      hydroxy-4-aminobiphenyl (N-OH-4-ABP), 4-aminobiphenyl (4-ABP) and 2-amino-1
      methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). IC(50) values determined for the
      sulfation of 17beta-estradiol by SULT1A1 were 11.8 microM, 28.2 microM, and 500
      microM, respectively, for N-OH-4-ABP, 4-ABP and PhIP. Kinetic analyses indicated
      that the mechanism underlying the inhibition of 17beta-estradiol sulfation by
      these cigarette smoke toxicants is of a mixed competitive-noncompetitive type.
      Metabolic labeling experiments clearly showed inhibition of the production of
      [(35)S]sulfated 17beta-estradiol by N-OH-4-ABP in a concentration-dependent
      manner in HepG2 cells. Taken together, these results suggest that sulfation plays
      a significant role in the metabolism of cigarette smoke compounds. By serving as
      substrates for SULTs, cigarette smoke toxicants may interfere with the metabolism
      of 17beta-estradiol and other endogenous compounds.

PMID- 17433397
TI  - BJ-48, a novel thrombin-like enzyme from the Bothrops jararacussu venom with high
      selectivity for Arg over Lys in P1: Role of N-glycosylation in thermostability
      and active site accessibility.
AB  - BJ-48, a serine protease from the venom of Bothrops jararacussu, was purified to
      homogeneity using affinity chromatography on p-aminobenzamidine-agarose followed
      by HPLC gel filtration. BJ-48 presented 52kDa by SDS-PAGE analysis and 48,036Da
      by electron spray mass spectrometry. The enzyme was shown to be highly
      glycosylated with 42% of N-linked carbohydrates composed of
      Fuc(1):GalN(4):GlcN(5):Gal(1):Man(2) and a high content of sialic acid residues
      (8-12%). BJ-48 had optimal esterase activity at pH 7.5 and displayed maximum
      catalytic rate at 50 degrees C. Its hydrolytic activity was strongly inhibited by
      aprotinin and dithiothreitol while N-tosyl-l-phenylalanine chloromethyl ketone, 6
      aminocaproic acid, E-64 and soybean trypsin inhibitor (SBTI) were ineffective.
      The kinetics of BJ-48 with chromogenic substrates revealed an unprecedented
      selectivity (10(4)-fold) for Arg over Lys in P1. BJ-48 proved to be a thrombin
      like enzyme (TLE) with a specific fibrinogen-clotting activity of 73.4NIH
      units/mg. The TLE rapidly digested human fibrinogen Bbeta chain, but the Aalpha
      chain was cleaved specifically to release fibrinopeptide A with k(cat)/K(m)=2.1
      microM(-1)s(-1). The TLE showed no activity toward other thrombin substrates like
      protein C, protease-activated receptor-1 or inhibitors such as hirudin and
      antithrombin. A non-denaturing procedure using PNGase F and neuraminidase
      followed by hydrophobic interaction chromatography was employed to obtain active
      BJ-48 forms with variable carbohydrate content. Compared to the native enzyme,
      total or partially deglycosylated BJ-48 forms presented up to 2-fold reduction in
      their specific activities upon heating at 55/65 degrees C or treatment with SBTI.
      These results point out a role for BJ-48 glycosylation in thermostability and
      controlling the access of some canonical protein inhibitors to the active site.

PMID- 17433399
TI  - No previews are good news: using preview search to probe categorical grouping for
      orientation.
AB  - We used the preview search procedure (Watson, D. G., & Humphreys G. W. (1997).
      Prioritising selection for new objects by top-down attentional inhibition of old
      objects. Psychological Review, 104, 90-122.) to examine distractor grouping in
      visual search for categorically-defined targets in the orientation dimension
      (Wolfe, J. M., Friedman-Hill, S. R., Stewart, M. I., & O'Connell, K. M. (1992).
      The role of categorization in visual search for orientation. Journal of
      Experimental Psychology: Human Perception and Performance, 18, 34-49).
      Participants searched for a relatively steep target presented amongst distractors
      of two shallow orientations. In a preview condition, the different distractors
      were presented in different time steps and search was found to be worse than a
      full-set baseline (Experiment 1). Further experiments determined this was not due
      to attentional capture by new distractors that were steeper than old items, nor
      to participants using different search strategies in the preview and full-set
      baselines. However, there were costs to performance when the old distractor group
      differed in orientation from the new distractors. We attribute the results to the
      preview condition disrupting grouping between distractors, with the different
      distractor groups then competing for selection with the target. An examination of
      the time-course of the preview effect suggested that grouping and segmentation
      was fast-acting, and separate from a process such as visual marking, involving
      the slow suppression of distractors over time. Under asynchronous presentation
      conditions, preview and new distractors that differ from the target orientation
      category, can compete rather than cooperate in grouping.

PMID- 17433398
TI  - Functional characterization of chimpanzee cytomegalovirus chemokine, vCXCL
      1(CCMV).
AB  - Human cytomegaloviruses (HCMVs) are important pathogens in immunocompromised
      patients and newborns. The viral chemokine, vCXCL-1, of the Toledo (Tol) strain
      of HCMV has been implicated in HCMV virulence. Chimpanzee CMV (CCMV) has several
      genes with similarity to the vCXCL-1(Tol) gene, UL146. In order to test whether
      the CCMV viral chemokine, vCXCL-1(CCMV), is similar to vCXCL-1(Tol), we
      characterized its function in vitro. Receptor binding, activation, chemotaxis,
      signaling, and apoptosis in neutrophils were compared between vCXCL-1(Tol) and
      vCXCL-1(CCMV) and host chemokines. Although the homologues had similar activation
      potentials, chemotactic properties, and signaling, vCXCL-1(CCMV) had a
      approximately 70-fold lower affinity for CXCR2 and displayed differences in
      integrin upregulation and neutrophil apoptosis. These data demonstrate that in
      spite of extensive amino acid variability in vCXCL-1, CCMV may provide a model
      for assessing the role of vCXCL-1 in CMV pathogenesis in vivo.

PMID- 17433400
TI  - Effects of pH and temperature on products and bacterial community in L-lactate
      batch fermentation of garbage under unsterile condition.
AB  - Acidogenesis fermentation of artificial garbage without sterile condition was
      conducted in batch mode to investigate effects of cultivation pH (5.5, 6.0, 6.5)
      and temperature (45, 50, 55 degrees C). Bacteria exiting natively in the garbage
      were utilized in this study; in turn, no specific seed was inoculated. The
      results indicated that only one set of operational conditions (pH 5.5 and 55
      degrees C) led to L-lactate fermentation. Obtained yield of lactate based on
      initial carbohydrate was around 0.5 and optical purity of L-lactate was around
      99%. In this study, three typical cases, which were L-lactate, racemic lactate
      and butyrate fermentation, were observed depended on sets of cultivation pH and
      temperature. Microbial structures of typical cases were also identified with
      using 16S rDNA libraries. The analysis indicated that Bacillus coagulans produced
      L-lactate. Lactobacillus amylolyticus, which produces racemic lactate, and
      Clostridium thermopalmarium, which produces butyrate, were also detected on each
      typical sample. L. amylolyticus and C. thermopalmarium would be eliminated by
      setting cultivation temperature of 55 degrees C and above, and pH 5.5 and below,
      respectively. From a series of this study, operational conditions of pH 5.5 and
      temperature of 55 degrees C would be potentially suitable for L-lactate
      fermentation of garbage with view of efficiency and stability of its production.

PMID- 17433401
TI  - Denitrification with methane as external carbon source.
AB  - Methane is a potentially inexpensive, widely available electron donor for
      biological denitrification of wastewater, landfill leachate or drinking water.
      Although no known methanotroph is able to denitrify, various consortia of
      microorganisms using methane as the sole carbon source carry out denitrification
      both aerobically and anaerobically. Aerobic methane-oxidation coupled to
      denitrification (AME-D) is accomplished by aerobic methanotrophs oxidizing
      methane and releasing soluble organics that are used by coexisting denitrifiers
      as electron donors for denitrification. This process has been observed in several
      laboratory studies. Anaerobic methane oxidation coupled to denitrification (ANME
      D) was recently discovered and was found to be mediated by an association of an
      archaeon and bacteria. Methane oxidizing consortia of microorganisms have also
      been studied for simultaneous nitrification and denitrification (SND) of
      wastewater. This review focuses on the AME-D process, but also encompasses
      methane oxidation coupled to SND as well as ANME-D.

PMID- 17433402
TI  - Selective heavy metals removal from waters by amorphous zirconium phosphate:
      behavior and mechanism.
AB  - Selective removal of heavy metals from water has been of considerable concern for
      several decades. In the present study, the amorphous zirconium phosphate (ZrP)
      was synthesized and characterized by X-ray photoelectron spectroscopy (XPS), X
      ray diffraction (XRD), scanning electron micrography (SEM), thermogravimetric
      analysis (TGA) as well as pH-titration experiments. Uptake of heavy metals
      including lead, cadmium, and zinc onto ZrP was studied by using a polystyrene
      sulfonic-acid exchanger D-001 as a reference sorbent and Ca(2+) as a competing
      cation due to its ubiquity in natural or industrial waters. The results indicated
      that the uptake of heavy metals onto ZrP is essentially an ion-exchange process
      and dependent upon solution pH. In comparison with D-001, ZrP exhibited more
      favorable sorption of heavy metals particularly in terms of high selectivity, as
      indicated by the distribution coefficients of ZrP even several orders higher than
      D-001 towards heavy metals when calcium ion coexisted at a high level in
      solution. The Fourier transform-infrared (FT-IR) spectroscopic investigation
      indicated that the uptake of calcium, cadmium, and zinc ions onto ZrP is only
      driven by the electrostatic interaction, while that of lead ion is possibly
      dependent upon the inner-sphere complex formation with ZrP. XPS results further
      elucidated that ZrP displays different sorption affinity towards heavy metals in
      the same order as selectivity sequence of Pb(2+)>Zn(2+) approximately
      Cd(2+)>Ca(2+), which can be explained by hard and soft acids and bases (HASB)
      theory. Moreover, uptake of heavy metals onto ZrP approached to equilibrium
      quickly and the used ZrP could be readily regenerated for reuse by the dilute HCl
      solution. Thus, all the results suggest that amorphous ZrP has excellent
      potential as a sorption material for water treatment.

PMID- 17433403
TI  - Oxidation of sulfamethoxazole and related antimicrobial agents by TiO2
      photocatalysis.
AB  - The widespread detection of pharmaceutically active compounds, including many
      synthetic antimicrobial agents, in aquatic environments is raising public health
      concerns. As a result, there is growing interest in the development of innovative
      technologies to efficiently transform these compounds to non-toxic and
      pharmaceutically inactive byproducts. This work examines the photocatalytic
      degradation of sulfamethoxazole (SMX) and related sulfonamide antimicrobial
      agents in aqueous suspensions of nanophase titanium dioxide (TiO(2)).
      Experimental results demonstrate that SMX is mineralized by TiO(2) irradiated
      with ultraviolet-A light (UVA: 324<<lambda<<400 nm). Rates of UVA-TiO(2)
      photocatalyzed SMX degradation are dependent upon several variables, including
      the initial SMX concentration, catalyst phase identity and concentration,
      electron acceptor identity and concentration, and the presence of non-target
      water constituents. In contrast, reaction rates are not sensitive to changes in
      sulfonamide structure. Although pH has little direct effect on reaction rates,
      the presence of natural organic matter (NOM) inhibits photocatalytic degradation
      of SMX to a much greater extent at pH 5 than pH 9. In addition, the presence of
      bicarbonate leads to enhanced SMX photocatalysis at pH 9. Kinetic trends are
      consistent with a mechanism involving sulfonamide oxidation by hydroxyl radicals
      ((*)OH) generated via TiO(2) band gap excitation by UVA radiation. Identified
      transformation intermediates and products are consistent with SMX mineralization
      initiated by (*)OH attack on either the aromatic or heterocyclic rings or the
      sulfonamide bond. Results demonstrate that UVA-TiO(2) photocatalysis can be a
      very effective approach for degrading sulfonamide micropollutants, particularly
      in natural waters exhibiting either alkaline pH or low concentrations of NOM, or
      both conditions.

PMID- 17433404
TI  - Uncertainty in prediction of disinfection performance.
AB  - Predicting the disinfection performance of a full-scale reactor in drinking water
      treatment is associated with considerable uncertainty. In view of quantitative
      risk analysis, this study assesses the uncertainty involved in predicting
      inactivation of Cryptosporidium parvum oocysts for an ozone reactor treating lake
      water. A micromodel is suggested which quantifies inactivation by stochastic
      sampling from density distributions of ozone exposure and lethal ozone dose. The
      ozone exposure distribution is computed with a tank in series model that is
      derived from tracer data and measurements of flow, ozone concentration and ozone
      decay. The distribution of lethal ozone doses is computed with a delayed Chick
      Watson model which was calibrated by Sivaganesan and Marinas [2005. Development
      of a Ct equation taking into consideration the effect of Lot variability on the
      inactivation of Cryptosporidium parvum oocysts with ozone. Water Res. 39(11),
      2429-2437] utilizing a large number of inactivation studies. Parameter
      uncertainty is propagated with Monte Carlo simulation and the probability of
      attaining given inactivation levels is assessed. Regional sensitivity analysis
      based on variance decomposition ranks the influence of parameters in determining
      the variance of the model result. The lethal dose model turns out to be
      responsible for over 90% of the output variance. The entire analysis is re-run
      for three exemplary scenarios to assess the robustness of the results in view of
      changing inputs, differing operational parameters or revised assumptions about
      the appropriate model. We argue that the suggested micromodel is a versatile
      approach for characterization of disinfection reactors. The scheme developed for
      uncertainty assessment is optimal for model diagnostics and effectively supports
      the management of uncertainty.

PMID- 17433405
TI  - Effectiveness of an alternating aerobic, anoxic/anaerobic strategy for
      maintaining biomass activity of BNR sludge during long-term starvation.
AB  - The effectiveness of an aerobic, anoxic/anaerobic strategy for maintaining the
      activity of activated sludge performing biological nitrogen and phosphorus
      removal during long-term starvation is investigated. A lab-scale sequencing batch
      reactor (SBR) treating abattoir wastewater and achieving high-levels (>95%) of
      nitrogen, phosphorus and COD removal was used. The reactor was put twice into a
      so-called "sleeping mode" for a period of 5-6 weeks when the abattoir, where the
      wastewater was sourced, was closed down for annual maintenance. The "sleeping
      mode" operation consisted of 15 min aeration in a 6 h SBR cycle. The sludge was
      allowed to settle in the remaining time of the cycle. The decay rates for ammonia
      oxidising bacteria (AOB) and nitrite oxidising bacteria (NOB) were determined to
      be 0.017 and 0.004 d(-1), respectively. These decay rates correlated well with
      AOB and NOB population quantified using molecular techniques (FISH). There was
      negligible phosphate accumulation in the reactor during the first 1-2 weeks of
      starvation, which was followed by a linear net release of phosphate in the
      remaining 4-5 weeks at a very slow rate of 1-2 mgP gVSS(-1)d(-1). A sudden
      decrease in the aerobic activities of polyphosphate accumulating organisms
      (PAOs), observed via anaerobic/aerobic batch tests, occurred after 2 weeks of
      starvation. This correlated with a dramatic increase of several metal ions in the
      liquid phase. The underlying reasons are not clear. A resuscitation period with a
      gradual increase of the wastewater load was applied during the re-startup of the
      reactor after both "sleeping mode" periods. Each time, the performance of the
      reactor in terms of nitrogen and phosphorus removal fully recovered in 4 days.

PMID- 17433406
TI  - Removal of particle-associated bacteriophages by dual-media filtration at
      different filter cycle stages and impacts on subsequent UV disinfection.
AB  - This bench-scale study investigated the passage of particle-associated
      bacteriophage through a dual-media (anthracite-sand) filter over a complete
      filter cycle and the effect on subsequent ultraviolet (UV) disinfection. Two
      model viruses, bacteriophages MS2 and T4, were considered. The water matrix was
      de-chlorinated tap water with either kaolin or Aldrich humic acid (AHA) added and
      coagulated with alum to form floc before filtration. The turbidity of the
      influent flocculated water was 6.4+/-1.5 NTU. Influent and filter effluent
      turbidity and particle counts were measured as well as headloss across the filter
      media. Filter effluent samples were collected for phage enumeration during three
      filter cycle stages: (i) filter ripening; (ii) stable operation; and (iii) end of
      filter cycle. Stable filter operation was defined according to a filter effluent
      turbidity goal of <0.3 NTU. Influent and filter effluent samples were
      subsequently exposed to UV light (254 nm) at 40 mJ/cm(2) using a low pressure UV
      collimated beam. The study found statistically significant differences
      (alpha=0.05) in the quantity of particle-associated phage present in the filter
      effluent during the three stages of filtration. There was reduced UV disinfection
      efficiency due to the presence of particle-associated phage in the filter
      effluent in trials with bacteriophage MS2 and humic acid floc. Unfiltered
      influent water samples also resulted in reduced UV inactivation of phage relative
      to particle-free control conditions for both phages. Trends in filter effluent
      turbidity corresponded with breakthrough of particle-associated phage in the
      filter effluent. The results therefore suggest that maintenance of optimum
      filtration conditions upstream of UV disinfection is a critical barrier to
      particle-associated viruses.

PMID- 17433407
TI  - Bacterial source tracking from diverse land use catchments by sterol ratios.
AB  - Water samples from sites potentially impacted by septic tanks, cattle, sewage
      treatment plant (STP) and natural forests were collected at regular monthly
      intervals and within 48 h of rainfall events between October 2004 and June 2006.
      All samples (n=296) were analysed for faecal coliforms and faecal sterols
      including coprostanol, epicoprostanol, cholestanol, cholesterol and 24
      ethylcoprostanol. Faecal sterol ratios were used to assign human and/or herbivore
      contamination sources and to estimate their percentage relative contributions in
      water samples. The catchments had significantly different profiles of designated
      contamination origins (p<0.05), which were consistent with land use patterns. The
      STP impacted site had the highest incidence of human contamination assignations
      and the highest mean levels of coprostanol, whilst the forested site had the
      highest incidence of uncontaminated samples and the lowest mean concentration of
      coprostanol. Coprostanol concentrations were not always correlated with faecal
      coliform counts.

PMID- 17433408
TI  - Study of biological stabilization processes of cattle and poultry manure by
      thermogravimetric analysis and (13)C NMR.
AB  - The biological stabilization process of cattle and poultry manure was studied
      using thermogravimetric analysis and (13)C nuclear magnetic resonance. The
      stabilization processes carried out were composting, anaerobic digestion and a
      mixed process (partly aerobic, partly anaerobic). It was observed from the
      analyzed samples that the biological stabilization processes reduce the volatile
      content of the bio-wastes and increase the degree of aromaticity. The
      stabilization of cattle manure by means of aerobic processes was able to further
      oxidize and enriched in aromatic compounds the bio-waste when compared with the
      digestion process. On the other hand, the stabilization of poultry manure
      resulted in a greater aromatization under the digestion process. Stabilized
      samples with a high degree of aromaticity presented a lower volatile content
      accompanied by a reduction in the intensity of the differential thermogravimetry
      peak registered under an inert atmosphere, indicative of the thermal
      decomposition of the organic matter. The thermal decomposition of all the
      analyzed materials (fresh and stabilized samples) commenced at around 200 degrees
      C but for the digested poultry manure, which decomposition initiated close to 250
      degrees C. All stabilized samples yielded a lower degree of volatilization to
      that one observed in fresh samples.

PMID- 17433409
TI  - Effects of long-term alachlor exposure on hepatic antioxidant defense and
      detoxifying enzyme activities in crucian carp (Carassius auratus).
AB  - Alachlor has been widely used in agriculture all over the world. It is suggested
      that it may be a carcinogen and also an environmental estrogen. In this paper,
      the physiological and biochemical perturbations of crucian carp (Carassius
      auratus) exposed to alachlor at different concentrations over 60 days were
      investigated. The gonadosomatic index (GSI) and hepatosomatic index (HSI) were
      measured. The activity of hepatic antioxidant defense and detoxifying enzymes,
      superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST)
      and the content of glutathione (GSH) were determined and compared with the
      control group. The result showed that GSI and HSI decreased significantly
      (P<0.05) in almost all treatments. The activities of SOD, CAT and GST were
      induced continuously (P<0.05), while the content of reduced glutathione (GSH) was
      inhibited on the whole. These changes reflect that the antioxidant systems of the
      tested fishes were affected. The possible defense mechanistic implications about
      the changes were thus discussed. Furthermore, hepatic SOD and GST were sensitive
      to alachlor at low concentration, indicating that they might be potential
      biomarkers in early detection of alachlor contamination in aquatic ecosystems.

PMID- 17433410
TI  - Polybrominated diphenyl ethers (PBDEs) in human milk from Australia.
AB  - Polybrominated diphenyl ethers (PBDEs) are flame retardants added to a multitude
      of products to reduce flammability. PBDEs have been widely detected and
      quantified in biota and humans in many industrialised countries from the Northern
      Hemisphere. However data concerning the levels of these compounds in the
      Australian population and environment remain limited. The objectives of this
      study were to determine PBDE concentrations and congener profiles in Australian
      human milk and compare this to concentrations found in other countries. Pooled
      human milk samples obtained from mothers residing in 12 regions of Australia were
      analysed by HRGC/HRMS for 18 PBDE congeners. In total, 157 human milk samples
      collected in 2002 and 2003 were divided into 17 regional pools. PBDEs were
      detected in all pools of human milk from Australia. The mean+/-standard deviation
      and median summation operatorPBDE concentrations were 11.1+/-3.2 and 11.0 ng g(
      1) lipid, respectively with a range of 6.1-18.7 ng g(-1) lipid. The congener
      profile was dominated by BDE-47 followed by BDE-99, -100, -153, -154 and -183.
      Regional differences were evaluated, but no trends were observed. The data
      suggest regional differences are likely to be small if they exist at all. The
      concentrations of PBDEs found in Australian human milk were lower than those
      reported from North America but higher than those reported from Europe and Asia.
      Our results suggest that the exposure pathways which contribute to the PBDE body
      burden in the Australian population require a better understanding in order to
      determine future policy regarding their use and disposal.

PMID- 17433411
TI  - Characteristics of leachate from pyrolysis residue of sewage sludge.
AB  - The pyrolysis residue (SP) of sewage sludge (SS) produced at 500 degrees C was
      subjected to batch and column leaching tests to investigate the release of its
      organic and inorganic constituents and metals. For comparison, incineration ash
      (SI) obtained from a SS incinerator was also tested. Pyrolysis and incineration
      reduced organic matter of SS from 0.78 kg kg(-1)-dry SS to 0.16 and 0.01 kg kg(
      1)-dry SS, respectively. Heavy metals remained in SP without being volatilized,
      although Cd and Pb were transferred into the off-gas during incineration. In the
      batch leaching test with the leaching liquid-to-solid mass ratio (L/S)=10, the pH
      of the SS, SP, and SI filtrates was 6.3, 7.9, and 11.0, respectively. The total
      organic carbon concentrations were in the order SS (877 l mg l(-1))>>SP (99 mg l(
      1))>SI (26 mg l(-1)). The SP and SI filtrates met the landfill standard for the
      Cd and Pb concentrations (<0.3 mg l(-1)). In the column tests, although the SP
      contained more organic matter than that of SI, its carbon discharge into the
      leachate under aerobic conditions was similar to that of SI under anaerobic
      conditions. The leaching of heavy metals, such as Cd, Cr, Pb, and Zn, was also
      suppressed in SP during the active decomposition of organic matter. We
      demonstrated that pyrolysis reduces the potential release of pollutants from
      sewage sludge in landfill, making it a promising method of treating sewage sludge
      before landfilling.

PMID- 17433412
TI  - Removal of phenols from water accompanied with synthesis of organobentonite in
      one-step process.
AB  - A novel technology of wastewater treatment was proposed based on simultaneously
      synthesis of organobentonite and removal of organic pollutants such as phenols
      from water in one-step, which resulted that both surfactants and organic
      pollutants were removed from water by bentonite. The effects of contact time, pH
      and inorganic salt on the removal of phenols were investigated. Kinetic results
      showed that phenols and cetyltrimethylammonium bromide (CTMAB) could be removed
      by bentonite in 25 min. The removal efficiencies were achieved at 69%, 92% and
      99%, respectively, for phenol, p-nitrophenol and beta-naphthol at the initial
      amount of CTMAB at about 120% cation exchange capacity of bentonite. Better
      dispersion property and more rapid bentonite sedimentation were observed in the
      process. The results indicated that the one-step process is an efficient, simple
      and low cost technology for removal of organic pollutants and cationic
      surfactants from water. The proposed technology made it possible that bentonite
      was applied as sorbent for wastewater treatment in industrial scale.

PMID- 17433413
TI  - The effect of physico-chemical parameters and chemical compounds on the activity
      of beta-d-galactosidase (B-GAL), a marker enzyme for indicator microorganisms in
      water.
AB  - The presence of coliforms in polluted water was determined enzymatically (in
      situ) by directly monitoring the activity of beta-d-galactosidase (B-GAL) through
      the hydrolysis of the yellow chromogenic subtrate, chlorophenol red beta-d
      galactopyranoside (CPRG), which produced a red chlorophenol red (CPR) product.
      The objectives of this study were to monitor the effect of compounds commonly
      found in the environment and used in water treatment on a B-GAL CPRG assay and to
      investigate the differences between the environmental B-GAL enzyme and the pure
      commercial enzyme. Environmental B-GAL was optimally active at pH 7.8. Two
      temperature optima were observed at 35 and 55 degrees C, respectively. B-GAL
      activity was strongly inhibited by silver and copper ions. While calcium and
      ferrous ions at lower concentrations (50-100mgl(-1)) increased the enzyme
      activity, a reduction was observed at higher concentrations (200mgl(-1)). Sodium
      hypochlorite, normally used in rural areas to disinfect water gradually decreased
      B-GAL activity at concentrations between 0 and 5600ppm for both the commercial
      and environmental enzymes. B-GAL from the environment behaved differently from
      its commercially available counterpart.

PMID- 17433414
TI  - Adaptation and functional integration in primate phylogenetics.
AB  - In two areas of phylogenetics, contrary predictions have been developed and
      maintained for character analysis and weighting. With regard to adaptation, many
      have argued that adaptive characters are poorly suited to phylogenetic analysis
      because of a propensity for homoplasy, while others have argued that complex
      adaptive characters should be given high weight because homoplasy in complex
      characters is unlikely. Similarly, with regard to correlated sets of characters,
      one point of view is that such sets should be collapsed into a single character-a
      single piece of phylogenetic evidence. Another point of view is that a suite of
      correlated characters should be emphasized in phylogenetics, again because
      recurrence of detailed similarity in the same suite of features is unlikely. In
      this paper, I discuss the theoretical background of adaptation and functional
      integration with respect to phylogenetic systematics of primates. Several
      character examples are reviewed with regard to their functional morphology and
      phylogenetic signal: postorbital structures, tympanic morphology, fusion of the
      mandibular symphysis, the tooth comb, strepsirrhine talar morphology, and the
      prehensile tail. It is clear when considering characters such as these that some
      characters are synapomorphic of major clades and at the same time functionally
      important. This appears particularly to be the case when characters are
      integrated into a complex and maintained as stable configurations. Rather than
      being simply a problem in character analysis, processes of integration may help
      to explain the utility of phylogenetically informative characters. On the other
      hand, the character examples also highlight the difficulty in forming a priori
      predictions about a character's phylogenetic signal. Explanations of patterns of
      character evolution are often clade-specific, which does not allow for a simple
      framework of character selection and/or weighting.

PMID- 17433415
TI  - Mercury contamination in the vicinity of a derelict chlor-alkali plant Part II:
      contamination of the aquatic and terrestrial food chain and potential risks to
      the local population.
AB  - This study investigated the environmental impact and level of risk associated
      with mercury (Hg) contamination near a derelict chlor-alkali plant in Pavlodar,
      Northern Kazakhstan. Several species of fish were sampled from the highly
      polluted Lake Balkyldak and the nearby river Irtysh, to assess the extent of Hg
      bioaccumulation in the aquatic food chain and potential human health risks. A
      small number of bovine tissue samples, water samples, soil and plant samples from
      a nearby village were also investigated in order to make a preliminary assessment
      of potential impacts on the terrestrial food chain. Mercury levels in fish caught
      from Lake Balkyldak ranged from 0.16 to 2.2 mg kg(-1) and the majority of fish
      exceeded current human health criteria for Hg. Interspecies comparisons indicated
      that Hg is accumulated in the order dace>carp>tench. Site-specific
      bioaccumulation factors (BAF) were calculated for THg, and were estimated for
      MeHg. Fish from the river Irtysh and floodplain oxbow lakes contained between
      0.075 and 0.159 mg kg(-1) of Hg and can be regarded as uncontaminated. Soils were
      found to be impacted by past atmospheric emissions of Hg. Cattle grazing in the
      surroundings of the factory are exposed to Hg from contaminated soils, plants and
      surface water, but the consumption of contaminated fish from the lake appears to
      be the main route of exposure for humans.

PMID- 17433416
TI  - Impact of different feeding strategies and plant presence on the performance of
      shallow horizontal subsurface-flow constructed wetlands.
AB  - The aim of this investigation was to evaluate the effect of continuous and
      intermittent feeding strategies on contaminant removal efficiency of shallow
      horizontal subsurface-flow constructed wetlands (SSF CWs). Also it was tested the
      effect of the presence of plant aboveground biomass on removal efficiency. Two
      experimental wetlands planted with common reed were subjected to a three-phase,
      10-month experiment involving a common source of settled urban wastewater with a
      hydraulic loading rate of 26 mm/d during the first and second phases and 39 mm/d
      during the third. In the first and second phases one of the wetlands was fed
      continuously while the other was fed intermittently. In the third phase both
      systems were operated intermittently, but in one the macrophyte aboveground
      biomass was cut in order to study the effect of plant aboveground biomass on the
      removal efficiency. The intermittently fed system presented systematically more
      oxidised environmental conditions and higher ammonium removal efficiencies (on
      average 80 and 99% for the first and the second phases respectively) compared
      with the continuously fed system (71 and 85%). The mass amount of ammonium
      removed ranged from 0.58 to 0.67 g N/m2 d for the intermittently fed system and
      from 0.52 to 0.58 g N/m2 d for the continuously fed system. Sulphate removal was
      higher in the continuously fed system (on average 76 and 79% for the first and
      second phases respectively) compared with the intermittently fed system (51 and
      58%). In the third phase the wetland that operated with aboveground biomass
      exhibited more oxidised environmental conditions and better removal efficiencies
      (on average 81% for COD and 98% for ammonium) than the wetland operated without
      aboveground biomass (73% for COD and 72% for ammonium). The results of this study
      indicate that the intermittent feeding strategy improved the removal of ammonium
      and the presence of aboveground biomass enhanced the removal of COD and ammonium.

PMID- 17433417
TI  - Comments on paper "Spectroscopic evidence of the marine origin of mucilages in
      the Northern Adriatic Sea".

PMID- 17433418
TI  - The association of alpha-fibrinogen Thr312Ala polymorphism and venous
      thromboembolism in the LITE study.
AB  - INTRODUCTION: The alpha-fibrinogen Thr312Ala variant has been shown to influence
      clot structure through increased factor XIII cross-linking and formation of
      thicker fibrin fibers. However, the effect of this common variant on risk of
      venous thromboembolism (VTE) is unclear. This paper reports the association
      between the Thr312Ala variant and VTE in the LITE study. MATERIALS AND METHODS:
      506 cases and 1014 controls frequency matched on age, sex, race, and study were
      drawn from two prospective studies and included in the analysis. Logistic
      regression was used to examine the association between Thr312Ala and VTE.
      RESULTS: In a logistic regression model minimally adjusted for the matching
      variables, the Thr312Ala TA and AA genotypes were associated with a significantly
      higher risk of VTE than the TT genotype (TA OR and 95% confidence interval 1.27
      [1.01-1.60], AA OR 1.49 [1.00-2.22]). Associations were similar in analyses of PE
      and DVT considered separately and across racial and study subgroups. The
      association between alpha-fibrinogen Thr312Ala and VTE was modified by both BMI
      and the FXIII Val34Leu variant; the combination of elevated BMI or FXIII Val34Leu
      with alpha-fibrinogen Thr312Ala conveyed lower odds of VTE than would be expected
      by an additive or multiplicative model of individual risk factors. CONCLUSIONS:
      These results suggest that alpha-fibrinogen Thr312Ala is involved in the
      pathogenesis of VTE and that its action may be modified by other VTE risk
      factors.

PMID- 17433419
TI  - The effect of Misoprostol, a prostaglandin E1 analog, on apoptosis in ischemia
      reperfusion-induced intestinal injury.
AB  - The aim of this study was to investigate whether Misoprostol, a synthetic
      prostaglandin (PG) E1 analog, has any effect on the prevention of apoptosis in
      ischemia-reperfusion (I/R)-induced intestinal injury. Thirty adult male Wistar
      albino rats were divided into three groups: group I=sham operated+saline; group
      II=I/R+saline; and group III=I/R+Misoprostol. Misoprostol (50microg/kg/d) was
      administered as an intragastric meal for 3 days. The terminal ileum was collected
      for histological and biochemical investigations. Apoptotic cells were detected by
      terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelled (TUNEL)
      reaction. Immunohistochemical analysis was performed to determine the
      distribution of inducible nitric oxide synthase (iNOS) and endothelial NOS
      (eNOS). Samples were also analyzed for malondialdehyde (MDA), superoxide
      dismutase (SOD), and glutathione peroxidase (GSH-Px). The number of TUNEL
      positive cells was higher in group II when compared to the other two groups
      (p<0.05). In group III this value was higher when compared to group I, but lower
      than group II (p<0.05). iNOS immunoreactivity was not detected in ileum sections
      of group I animals, but moderate immunoreactivity was seen in group II and mild
      immunoreactivity in group III. The immunoreactivity of eNOS was moderate in ileum
      sections of all three groups. In ileum tissue, MDA was found to be higher in
      group II compared to group I (p<0.05), but there was no difference in group III.
      SOD was not different between groups I and III, but was significantly higher in
      group II (p<0.05). In our experimental model of I/R-induced intestinal injury,
      apoptosis is induced in enterocytes, whereas Misoprostol decreases enterocyte
      apoptosis in this experimental model. Our results indicate that Misoprostol may
      play a key role in the pathophysiologic events leading to failure of the
      intrinsic gut barrier defense mechanisms of intestinal epithelium.

PMID- 17433420
TI  - Abandon the intrauterine catheter and delay the cerclage in a radical
      trachelectomy.

PMID- 17433421
TI  - Demons syndrome revisited: a review of the literature.
AB  - OBJECTIVES: To report various descriptions of the combination of a benign genital
      tumour with pleural and/or abdominal effusion throughout the years and to
      determine the paternity of this syndrome, commonly known as Meigs' syndrome.
      METHODS: A systematic review of the literature from 1728 to 2004. RESULTS: Before
      1880, publications were rare and limited to clinical and anatomical descriptions
      drawing no conclusions between the cause and effect of this condition and even
      less about its management. Demons described the syndrome between 1887 and 1902.
      He was the first to specify that removal of the tumour (benign ovarian cyst,
      solid ovarian tumour, fibroma of the broad ligament) was essential for the
      patient to be cured of the effusions and that it was wrong to postpone surgery.
      In 1937, Meigs arrived at the same findings concerning ovarian fibromas and
      granulosa cell tumours, hence the name of Demons-Meigs which was given to this
      syndrome with the agreement of Meigs. Current literature reports on
      pseudosyndromes of Demons-Meigs including genital malignancies with negative
      cytology. These entities should not be called Demons or Meigs pseudosyndromes.
      Inversely, all benign tumours of the genital tract should be included in Demons
      syndrome, even if Demons did not actually encounter any during his years of
      practice, but it was in the spirit of his observations. CONCLUSION: Demons'
      syndrome includes all benign genital tumours, the Demons-Meigs eponym is reserved
      for the description of ovarian fibromas and granulosa cell tumours, and the
      Demons' pseudosyndrome includes all other entities.

PMID- 17433422
TI  - The outcomes of ovarian cancer treatment are better when provided by gynecologic
      oncologists and in specialized hospitals: a systematic review.
AB  - OBJECTIVE: There is much debate on the effect of specialized care for ovarian
      cancer patients. In this review we present an overview and summary of the recent
      literature on this subject. METHODS: The Pubmed database was searched for studies
      on the relationship between care setting (type of gynecologist or hospital) and
      care outcomes which were published between January 1991 and November 2006.
      Studies were included if they were of sufficient quality and included patients
      treated from 1990 onwards. RESULTS: Nineteen articles were retrieved. There were
      no randomized controlled trials on this subject. Staging and debulking were
      consistently found to be performed more adequately by gynecologic oncologists
      (pooled relative risk of optimal debulking by a gynecologic oncologist to <2 cm
      residual disease 1.4 (95%CI 1.2-1.5) and to no macroscopic disease 2.3 (95%CI 1.5
      3.5)) and in specialized hospitals (odds ratios for optimal debulking varied
      between 1.9 and 6.0). There were no differences in postoperative complication
      rates between different providers. Chemotherapy was given 1-15% more often in
      specialized settings. Differences in chemotherapy did not lead to differences in
      survival of patients treated by gynecologic oncologists, but did influence the
      effect of hospital on survival. Long-term survival was better after treatment in
      a specialized hospital. Surgery by a gynecologic oncologist resulted in longer
      survival in subgroups of patients, leading to a 5- to 8-month median survival
      benefit for patients with advanced stage disease. CONCLUSIONS: The outcome of
      ovarian cancer is better when treatment is provided by a gynecologic oncologist
      or in a specialized hospital.

PMID- 17433423
TI  - A study to evaluate the utility of presurgical CA125 to predict optimal tumor
      cytoreduction of epithelial ovarian cancer.
AB  - OBJECTIVE: To determine the ability of a preoperative serum CA125 to predict
      optimal primary tumor cytoreduction in patients with stage III and IV epithelial
      ovarian cancer (EOC). MATERIALS AND METHODS: The records of patients with
      advanced stage who underwent primary surgery for EOC at Tehran University, Vali
      Asr Hospital between 2000 and 2002 were reviewed. Inclusion criteria included
      FIGO stage III/IV disease, surgery by gynecologic oncology faculty, preoperative
      CA125, and an operative note clearly defining volume of residual disease. Without
      optimal cytoreduction was determined using the receiver operator curve (ROC).
      RESULTS: One hundred and twenty cases of advanced stage EOC were identified, of
      which 90 cases of stage III/IV met our inclusion criteria. Serum CA125 < or = 400
      was identified with OD > or = 75% of the time. Conversely, optimal cytoreduction
      was performed in < or = 40% of patients with CA125 > or =4000. The area under the
      ROC curve for CA125 was 0.680. The optimal cytoreduction rate for those with and
      without ascites was 38% and 77%, respectively (P<0.001). In a multivariate
      analysis using CA125, age, and ascites, the area under the curve was 0.696.
      CONCLUSION: We conclude that CA125 level did not reliably predict optimal
      cytoreduction in patients with stage III-IV EOC.

PMID- 17433424
TI  - Prognostic factors in pathologic parametrium-positive patients with stage IB-IIB
      cervical cancer treated by radical surgery and adjuvant therapy.
AB  - OBJECTIVE: The purpose of the present study was to identify prognostic factors
      and recurrent patterns in pathologic parametrium-positive patients with stage IB
      IIB cervical cancers treated by radical surgery and adjuvant therapy. METHODS:
      The patient population consisted of 84 individuals presenting with stage IB-IIB
      cervical cancers and histologically proven parametrial invasion. All these
      patients were treated postoperatively with adjuvant external whole pelvic
      irradiation, combination chemotherapy, or chemoradiotherapy. RESULTS: The 5-year
      disease-free survival rate was found to be 67.2% and 5-year overall survival
      rate, 75.4%. Multivariate analysis revealed that vaginal invasion (p=0.0008),
      lymph node metastasis (p=0.002), and non-squamous histology (p=0.010) were
      independent indicators of the disease-free survival rates and that the vaginal
      invasion (p=0.009) and lymph node metastasis (p=0.011) were independent
      prognostic factors for the overall survival rates. The 5-year overall survival
      rate was approximately 90% for patients without these risk factors. Disease
      recurrence was observed in 26 patients (31.0%) with a median time of 16.5 months
      (range, 5-59 months) from the surgery. Hematogenous recurrences, including those
      in the lung, liver, and bone, were significantly higher in patients with non
      squamous cell carcinomas (p=0.008). Distant lymph node recurrences were
      significantly higher in patients with positive pelvic lymph node and vaginal
      invasion (p=0.004 and p=0.023, respectively). Pelvic recurrences were
      significantly higher in patients with vaginal invasion (p=0.026). CONCLUSIONS:
      Vaginal invasion and lymph node metastasis are independent indicators for disease
      free and overall survival rates in pathologic parametrium-positive patients with
      stage IB-IIB cervical cancer treated by radical surgery and adjuvant therapy. The
      survival rate is excellent in the patients without these risk factors.
      Hematogenous recurrence may be evident in patients with non-squamous cell
      carcinomas.

PMID- 17433425
TI  - Significant differences of lymphocytes isolated from ascites of patients with
      ovarian cancer compared to blood and tumor lymphocytes. Association of CD3+CD56+
      cells with platinum resistance.
AB  - OBJECTIVES: Tumor infiltrating lymphocytes (TILs) and T regulatory cells (Tregs)
      have been associated with prognosis in ovarian cancer, but their prognostic
      significance in ascites has not been studied. We performed a prospective study of
      T lymphocytes isolated from ascites from patients with ovarian carcinoma and we
      compared them with the respective populations in blood and tumors. METHODS:
      Mononuclear cells from ascites (n=71) and blood were isolated by Ficoll, while
      tumor lymphocytes (n=20) were obtained upon mechanical dissociation. Phenotypic
      analysis was performed with flow cytometry. Ascites from 10 patients with
      cirrhosis was used as control. RESULTS: Tregs containing CD4(+)CD25(+) cells, NK
      T containing CD3(+)CD56(+) cells and CD69 and HLADR expression of CD4 and CD8
      lymphocytes were significantly increased in tumor ascites compared to blood and
      control ascites. A selective accumulation of these populations in the ascites of
      cancer patients, was suggested by the significantly higher ascites/blood (A/B)
      ratios in cancer patients but not controls. Cancer cell content in ascites was
      correlated with CD4(+)CD25(+), CD4(+)CD69(+), CD4(+)HLADR(+) and CD8(+)CD69(+)
      cells. There was no correlation of lymphocyte populations between ascites and
      samples from peritoneal metastases. Higher tumor grade was associated with
      increased A/B CD4(+)CD25(+) ratio and reduced CD3(+)CD56(+) cells, while platinum
      resistance was associated with reduced A/B CD3(+)CD56(+) ratio. CONCLUSIONS:
      There are significant differences of CD3(+)CD56(+) and CD25(+)CD4(+) lymphocytes
      and increase in lymphocyte activation between blood, ascites and peritoneal
      metastases from patients with ovarian cancer. The selective accumulation of
      CD3(+)CD56(+) population in ascites may be a predictive factor for platinum
      resistance.

PMID- 17433427
TI  - Modifiable family and school environmental factors associated with smoking status
      among adolescents in Guangzhou, China.
AB  - OBJECTIVE: To identify modifiable family and school environmental factors
      associated with Chinese adolescent smoking behaviors including never-smoking,
      experimental smoking, regular smoking, and attempting to quit. METHODS: A cross
      sectional survey using self-reported questionnaires was conducted in Huangpu,
      Guangzhou in December of 2004. A total of 3957 pupils agreed to complete the
      questionnaires. The prevalence odds ratio (risk) of experimental smoking was
      compared to never-smoking, adjusting for gender and age in unconditional logistic
      regression analysis. The risk of regular smoking was compared to experimental
      smoking, and the risk of attempting quitting was analyzed in regular smokers.
      RESULTS: The cigarette smoking of peers, mothers, fathers, brothers, and
      supervising teachers, passive smoking, and seeing someone smoking on campus
      increased the risk of experimental smoking vs. nonsmoking, while no-smoking
      signs, perceived anti-tobacco atmosphere in school, and being taught smoking
      related health knowledge decreased the risk. The factors associated with regular
      smoking compared to experimental smoking included the smoking of peers, brothers,
      fathers and supervising teachers, teacher's tolerance, and passive smoking. Being
      taught smoking-related knowledge, perceived anti-tobacco atmosphere and no
      smoking signs in school were positively associated with regular smoker's attempt
      to quit, while supervising teacher's smoking, parents' and teachers' tolerance
      could delay it. CONCLUSIONS: These modifiable family and school environmental
      factors as well as their interaction with gender and age should be highly
      considered in adolescent smoking prevention in China.

PMID- 17433428
TI  - Seasonal variations in antioxidant enzyme activity in ram seminal plasma.
AB  - Seminal oxidative stress status is emerging as a significant prognostic tool in
      assisted reproductive technology. A dynamic interplay between pro- and anti
      antioxidant substances in the ejaculate is essential. In this study, we
      determined seasonal changes in the activity of the antioxidant enzyme defense
      system comprising superoxide dismutase (SOD), glutathione reductase (GR),
      glutathione peroxidase (GPx) and catalase (CAT) in seminal plasma (SP) of mature
      Rasa Aragonesa rams. This breed corresponds to a local Spanish genotype with a
      short seasonal anoestrus between May and July. In addition, the activity of these
      enzymes was measured in protein fractions isolated from ram SP by exclusion
      chromatography. Total protein content in ram SP was higher during the breeding
      season (October-February) with a significantly higher value in first ejaculates.
      Antioxidant enzyme activities were higher during the non-breeding season (March
      September). Comparing first and second ejaculates, SOD and CAT activities were
      higher in the first of all months. However, GR and GPx activities changed
      throughout the year. Thus, GR activity was higher in July and August in first
      ejaculates, this difference being significant in July (4.53 versus 2.37 nmol
      substrate/minmg protein, P<0.05). Conversely, GPx activity was significantly
      higher in September and November in second ejaculates (21.1 versus 6.81 and 10.91
      versus 5.33, respectively, P<0.05). After SP fractionation by exclusion
      chromatography, GR activity was located in fractions 1 and 2 being irrelevant in
      the following peaks, and CAT activity was not detected all along the
      chromatographic profile. GPx and SOD activities were spread out along all
      fractions with a main peak in fractions 6 and 7. Given that these two fractions
      showed the greatest capacity to recover and prevent cold-shock membrane injury
      [Barrios B, Perez-Pe R, Gallego M, Tato A, Osada J, Muino-Blanco T, Cebrian-Perez
      JA. Seminal plasma proteins revert the cold-shock damage on ram sperm membrane.
      Biol Reprod 2000;63:1531-7, Barrios B, Fernandez-Juan M, Muino-Blanco T, Cebrian
      Perez J. Immunocytochemical localization and biochemical characterization of two
      seminal plasma proteins that protect ram spermatozoa against cold shock. J Androl
      2005;26:539-49], we could suggest that the protective effect might be, at least
      partially, due to the antioxidant enzyme activity.

PMID- 17433426
TI  - Passive smoke exposure trends and workplace policy in the Coronary Artery Risk
      Development in Young Adults (CARDIA) study (1985-2001).
AB  - OBJECTIVE: There has been reduced active smoking, decreased societal acceptance
      for smoking indoors, and changing smoking policy since the mid-1980s. We
      quantified passive smoke exposure trends and their relationship with workplace
      policy. METHOD: We studied 2504 CARDIA participants (Blacks and Whites, 18-30
      years old when recruited in 1985-86 from four US cities, reexamination 2, 5, 7,
      10, and 15 years later) who never reported current smoking and attended
      examinations at 10 or 15 years. RESULTS.: In non-smokers with a college degree
      (n=1581), total passive smoke exposure declined from 16.3 h/week in 1985/86 to
      2.3 h/week in 2000/01. Less education tended to be associated with more exposure
      at all timepoints, for example, in high school or less (n=292) 22.2 h/week in
      1985/86 to 8.5 h/week in 2000/01. Those who experienced an increase in the
      restrictiveness of self-reported workplace smoking policy from 1995/96 to 2000/01
      were exposed to almost 3 h per week less passive smoke than those whose workplace
      policies became less restrictive in this time period. CONCLUSIONS: The increasing
      presence of restrictive workplace policies seemed to be a component of the
      substantial decline in self-reported passive smoke exposure since 1985.

PMID- 17433429
TI  - Gesture, brain, and language.

PMID- 17433430
TI  - Inflection and computational load in agrammatic speech.
AB  - In this study we investigate the production of verb inflection in agrammatic
      aphasia. In a number of recent studies it has been argued that tense inflection
      is harder to produce for agrammatic individuals than agreement inflection.
      However, results are still inconclusive, at least for Dutch and German. Here, we
      report three experiments in which this matter is further investigated. Our first
      goal was to determine whether tense was indeed more difficult to produce than
      agreement. Also, we investigated whether error rates were influenced by
      computational load. The results for nine Dutch-speaking agrammatic participants
      generally indicated that tense was indeed harder to produce than agreement, but
      that for both types of inflection, the number of errors increased with
      computational load. Taking care of word order and inflection induced more errors
      than taking care of just inflection. These findings are discussed in relation to
      current processing and representational models of agrammatic production.

PMID- 17433431
TI  - The role of the immune system in preeclampsia.
AB  - Recent data demonstrate that an altered immune response may play a key role in
      the development of preeclampsia. Some epidemiological findings and animal models
      support this idea. In this article, we review the innate immune system and
      adaptive immune system in preeclampsia and discuss the pathophysiology of
      preeclampsia from an immunological viewpoint. The most characteristic
      immunological finding in preeclampsia is the activation of both the innate and
      adaptive immune system. Activated neutrophils, monocytes, and NK cells initiate
      inflammation which induce endothelial dysfunction, and activated T cells may
      support inadequate tolerance during pregnancy. The cytokine profile in
      preeclampsia shows that the production of type 1 cytokines, which induce
      inflammation, is dominant while the production of type 2 cytokines, which
      regulates inflammation, is suppressed. Furthermore, the immunoregulatory system
      is down-regulated in preeclampsia and persistent inflammation reduces regulatory
      T cell function. Therefore, systematical immunoactivation may be one cause of
      preeclampsia.

PMID- 17433432
TI  - Anti-proliferative activity of oversulfated fucoidan from commercially cultured
      Cladosiphon okamuranus TOKIDA in U937 cells.
AB  - Fucoidan from Cladosiphon okamuranus and its sulfate derivatives were prepared.
      Sulfate contents of native and oversulfated fucoidan were estimated to be 13.5%
      and 32.8%, respectively. The results of (1)H NMR suggest that 2,4-di-O-sulfo-, 2
      mono-O-sulfo- and 4-mono-O-sulfo-l-fucopyranose were involved in oversulfated
      fucoidan and 4-mono-O-sulfo-l-fucopyranose was involved in native fucoidan. The
      oversulfated fucoidan reduced the proliferation of U937 cells in a dose-dependent
      manner, but the activity of native fucoidan was weak. The sulfate content and
      substituting position of sulfate group might be important factors of anti
      proliferative activity in U937 cells. To examine whether the anti-proliferative
      activity of oversulfated fucoidan was caused by induction of apoptosis, apoptosis
      assay, caspase-3 activity assay and Western blotting analysis were performed.
      These results indicated that the oversulfated fucoidan induced apoptosis via
      caspase-3 and -7 activation-dependent pathway.

PMID- 17433433
TI  - Towards improved artificial lungs through biocatalysis.
AB  - Inefficient CO(2) removal due to limited diffusion represents a significant
      barrier in the development of artificial lungs and respiratory assist devices,
      which use hollow fiber membranes (HFMs) as the blood-gas interface and can
      require large blood-contacting membrane area. To offset the underlying
      diffusional challenge, "bioactive" HFMs that facilitate CO(2) diffusion were
      prepared via covalent immobilization of carbonic anhydrase (CA), an enzyme which
      catalyzes the conversion of bicarbonate in blood to CO(2), onto the surface of
      plasma-modified conventional HFMs. This study examines the impact of enzyme
      attachment on the diffusional properties and the rate of CO(2) removal of the
      bioactive membranes. Plasma deposition of surface reactive hydroxyls, to which CA
      could be attached, did not change gas permeance of the HFMs or generate membrane
      defects, as determined by scanning electron microscopy, when low plasma discharge
      power and short exposure times were employed. Cyanogen bromide activation of the
      surface hydroxyls and subsequent modification with CA resulted in near monolayer
      enzyme coverage (88%) on the membrane. The effect of increased plasma discharge
      power and exposure time on enzyme loading was negligible while gas permeance
      studies showed enzyme attachment did not impede CO(2) or O(2) diffusion.
      Furthermore, when employed in a model respiratory assist device, the bioactive
      membranes improved CO(2) removal rates by as much as 75% from physiological
      bicarbonate solutions with no enzyme leaching. These results demonstrate the
      potential of bioactive HFMs with immobilized CA to enhance CO(2) exchange in
      respiratory devices.

PMID- 17433434
TI  - Ex vivo expansion of rat bone marrow mesenchymal stromal cells on microcarrier
      beads in spin culture.
AB  - Bone marrow mesenchymal stromal cells (BM-MSC) are attractive candidates for
      connective tissue regeneration. Currently, their use is limited by poor overall
      cell survival and high apoptosis rates upon transplantation in vivo. We
      hypothesized that disruption of cell-extracellular matrix contact either during
      cell expansion or immediately prior to cell transplantation may impair cell
      viability and facilitate apoptosis. We therefore investigated whether BM-MSC can
      be expanded on microcarrier beads in spin culture and directly transplanted. This
      novel approach removes the need for the repeated trypsinizations that are usually
      required for expansion and transplantation. CultiSpher-S gelatin microcarrier
      beads supported Fisher and transgenic green fluorescent protein (GFP)(+) Sprague
      Dawley rat BM-MSC expansion. Bead-expanded BM-MSC could still be differentiated
      along the chondrogenic, osteogenic and adipogenic lineages. In the short term,
      direct subcutaneous transplantation of cells expanded on microcarriers was
      associated with significantly less apoptosis than trypsinized control cells. In
      the long term, BM-MSC expanded on microcarrier beads induced de novo trabecular
      bone formation in vivo. This novel approach present several advantages over
      current expansion-transplantation protocols for mesenchymal tissue regeneration.

PMID- 17433435
TI  - In vivo TRPC functions in the cardiopulmonary vasculature.
AB  - Cardiovascular diseases are the leading cause of death in the industrialized
      countries. The cardiovascular system includes the systemic blood circulation, the
      heart and the pulmonary circulation providing sufficient blood flow and oxygen to
      peripheral tissues and organs according to their metabolic demand. This review
      focuses on three major cell types of the cardiovascular system: myocytes of the
      heart as well as smooth muscle cells and endothelial cells from the systemic and
      pulmonary circulation. Ion channels initiate and regulate contraction in all
      three cell types, and the identification of their genes has significantly
      improved our knowledge of signal transduction pathways in these cells. Among the
      ion channels expressed in smooth muscle cells, cation channels of the TRPC family
      allow for the entry of Na(+) and Ca(2+). Physiological functions of TRPC1, TRPC3,
      TRPC4, TRPC5, TRPC6 and TRPC7 in the cardiovascular system, dissected by down
      regulating channel activity in isolated tissues or by the analysis of gene
      deficient mouse models, are reviewed. Possible functional roles and physiological
      regulation of TRPCs as homomeric or heteromeric channels in these cell types are
      discussed. Moreover, TRP channels may also be responsible for pathophysiological
      processes of the cardiovascular system like hypertension as well as cardiac
      hypertrophy and increased endothelial permeability.

PMID- 17433437
TI  - Incidence of hyperthyroidism after unrelated donor allogeneic stem cell
      transplantation.
AB  - We report on three patients who developed overt thyrotoxicosis after volunteer
      unrelated donor bone marrow transplantation for Philadelphia chromosome positive
      chronic myeloid leukemia shortly after the onset of chronic graft versus host
      disease. In all three cases, the etiology of hyperthyroidism is likely to be a
      combination of toxic factors and an immune process. Systematic evaluation of
      thyroid function tests in 97 unrelated allograft recipients from our center who
      survived at least 100 days from stem cell or bone marrow transplantation for
      hematological diseases gave a rate of overt thyrotoxicosis at 3.1% in this
      cohort.

PMID- 17433436
TI  - Isoform-specific up-regulation of plasma membrane Ca2+ATPase expression during
      colon and gastric cancer cell differentiation.
AB  - In this work we demonstrate a differentiation-induced up-regulation of the
      expression of plasma membrane Ca2+ATPase (PMCA) isoforms being present in various
      gastric/colon cancer cell types. We found PMCA1b as the major isoform in non
      differentiated cancer cell lines, whereas the expression level of PMCA4b was
      significantly lower. Cell differentiation initiated with short chain fatty acids
      (SCFAs) and trichostatin A, or spontaneous differentiation of post-confluent cell
      cultures resulted in a marked induction of PMCA4b expression, while only
      moderately increased PMCA1b levels. Up-regulation of PMCA4b expression was
      demonstrated both at the protein and mRNA levels, and closely correlated with the
      induction of established differentiation markers. In contrast, the expression
      level of the Na+/K+-ATPase or that of the sarco/endoplasmic reticulum Ca2+ATPase
      2 protein did not change significantly under these conditions. In membrane
      vesicles obtained from SCFA-treated gastric/colon cancer cells a marked increase
      in the PMCA-dependent Ca2+ transport activity was observed, indicating a general
      increase of PMCA function during the differentiation of these cancer cells.
      Because various PMCA isoforms display distinct functional characteristics, we
      suggest that up-regulated PMCA expression, together with a major switch in PMCA
      isoform pattern may significantly contribute to the differentiation of
      gastric/colon cancer cells. The analysis of PMCA expression may provide a new
      diagnostic tool for monitoring the tumor phenotype.

PMID- 17433438
TI  - Caregiver commitment to foster children: the role of child behavior.
AB  - OBJECTIVE: This study aimed to examine the association between child behavior
      problems and caregiver commitment to their child in a group of young foster
      children. METHOD: The sample consisted of 102 caregiver-child dyads from the
      greater Baltimore area. Child behavior was assessed using the Child Behavior
      Checklist [CBCL; Achenbach, T. M. (1991). Manual for the Child Behavior
      Checklist/4-8 and 1991 profile. Burlington, VT: University of Vermont, Department
      of Psychiatry; Achenbach, T. M. (1992). Manual for the Child Behavior Checklist/2
      3 and 1992 profile. Burlington, VT: University of Vermont, Department of
      Psychiatry], and caregiver commitment was assessed using a semi-structured
      interview known as the "This is My Baby" Interview [Bates, B., & Dozier, M.
      (1998). "This Is My Baby"coding manual. Unpublished manuscript, University of
      Delaware, Newark]. For a sub-sample of the dyads (N=76), we examined caregiver
      commitment and parent-reported child behavior at two time points in order to
      examine the stability of a caregiver's commitment over time and to examine the
      direction of the association between the two variables. RESULTS: Overall,
      caregiver reported child behavior was significantly associated with caregiver
      commitment. Both caregiver reported child behavior and caregiver commitment were
      highly stable over an 11-month period. When we examined the data over time, the
      effect of caregiver reported child behavior at time 1 on caregiver commitment at
      time 2 was not significantly larger than the effect of caregiver commitment at
      time 1 on caregiver reported child behavior at time 2. As a result, we were not
      able to determine the direction of the association between caregiver reported
      child behavior and caregiver commitment. CONCLUSIONS: Our results indicate that
      caregiver reported child behavior is significantly associated with caregiver
      commitment to their foster children, even after controlling for factors including
      age of entry into foster care and time in placement.

PMID- 17433439
TI  - Phenanthrene release from natural organic matter surrogates under simulated human
      gastrointestinal conditions.
AB  - The aliphatic region of natural organic matter (NOM) can retain polycyclic
      aromatic hydrocarbons (PAH) due to the presence of non-polar binding sites. Thus
      NOM may act as a vehicle for entry of PAH into the gastrointestinal system in man
      and animals. In this study, the release of phenanthrene from the aliphatic NOM
      surrogates cutin and cutan was measured under simulated human gastrointestinal
      formulations using three treatments designed to simulate the biological and
      chemical conditions of the gastrointestinal environment. The three experimental
      treatments were composed of fecal microorganisms, chyme, and chyme+fecal
      microorganisms. Water was used as a control treatment. Phenanthrene laden
      biopolymer and a C18 membrane were immersed in each treatment. Phenanthrene was
      extracted from each membrane and measured with HPLC. Membrane-associated
      phenanthrene was taken to represent the fraction that had desorbed from the
      biopolymer. Cutin was found to yield an average phenanthrene release 55% higher
      than cutan (94% vs. 39%). A significant decrease (p<0.05) in phenanthrene release
      was observed in both the chyme and chyme+fecal microorganism treatments as
      compared to the water treatment (control). The presence of enteric microorganisms
      did not significantly influence phenanthrene release and did not reduce
      phenanthrene bioaccessibility in gastrointestinal chyme. Over 80% of the
      phenanthrene in cutin was recovered in the C18 matrix and its relative amount was
      uninfluenced by the treatments. For cutan, only 25-50% of the phenanthrene was
      recovered, suggesting that cutin-associated phenanthrene was more loosely bound.
      These data demonstrate that the fractions of NOM retained phenanthrene to a
      varying extent and thus the predictions of phenanthrene bioavailability should
      also be assessed on the basis of the constituents of the NOM matrix.

PMID- 17433440
TI  - Short-term effects of benzalkonium chloride and atrazine on Elodea canadensis
      using a miniaturised microbioreactor system for an online monitoring of
      physiologic parameters.
AB  - The study evaluated the effects of benzalkonium chloride (BAC) and atrazine on
      the macrophyte Elodea canadensis (Michaux) using a miniaturised monitoring test
      system consisting of a microbioreactor of reduced volume and integrated sensors
      for the online measurement of physiologic parameters, like oxygen production and
      different parameters of fluorescence. Different concentrations of both chemicals
      were applied to leaves of E. canadensis and the physiologic endpoints evaluated
      after 1h. A concentration-dependent reduction of the oxygen production and of the
      effective quantum yield of energy conversion was recorded. The mini-PAM technique
      implemented in the presented system allowed for a clear monitoring of the kinetic
      of BAC and atrazine, showing their distinct mode of action. No observable adverse
      effects were recorded up to concentrations of 2.5 mg/L and 10 microg/L, for BAC
      and atrazine, respectively. These values are in accordance with available results
      in the literature, hence indicating that the microbioreactor test system might be
      suitable, on the one hand, for the laboratory screening of potential short-term
      toxicity of contaminants on aquatic plants, and on the other hand, serve as an in
      situ field biomonitoring system for the rapid detection of pollutants in water.

PMID- 17433441
TI  - Clinical and epidemiological investigation of chronic upper respiratory diseases
      caused by beta-haemolytic Streptococci in horses.
AB  - An outbreak of strangle-like disease involving 26 horses farmed in central Italy
      was investigated by clinic examination, endoscopy, cytology, bacteriology and
      polymerase chain reaction (PCR). At weekly interval, a total of three nasal swabs
      and one guttural pouches lavage fluid (GPLF) were collected, and no Streptococcus
      equi subsp. equi carrier was found. Some horses showed upper airways disease and
      endoscopic signs of pharyngeal lymphoid hyperplasia of different grade and/or
      abnormal endoscopic appearance of guttural pouches. Streptococcus dysgalactiae
      subsp. equisimilis was isolated from 14 horses while S. equi subsp. zooepidemicus
      was isolated from six horses. PCR confirmed the biochemical and serological
      identification of all isolates and was positive in 10 bacteriological negative
      samples. The absence of S. equi and the frequent detection of S. equisimilis and
      S. zooepidemicus suggest that beta-haemolytic streptococci other than S. equi
      could be the causative agent of strangle-like disease.

PMID- 17433442
TI  - The impact of diet on anti-social, violent and criminal behaviour.
AB  - The role of diet in anti-social behaviour was considered, paying particular
      attention to double-blind placebo-controlled trials. Meta-analysis of five well
      designed studies found that elimination diets reduced hyperactivity-related
      symptoms, producing a summary standardized mean difference (SSMD) of 0.80 (95% CI
      0.41-1.19). The picture was of children potentially responding to a wide range of
      food items although the pattern was individual to the child. Supplementation with
      poly-unsaturated fatty acids decreased violence (SSMD -0.61, 95% CI -0.83 to 
      0.39) although there was no evidence of an influence on hyperactivity. Three well
      designed studies have reported that vitamin/mineral supplementation reduced anti
      social behaviour. There are also findings of an association between a tendency to
      develop low blood glucose and aggression. Many responses to diet were
      idiosyncratic and involved a wide range of foods interacting with individual
      differences in physiology. Reactions were not observed in all members of groups
      chosen because they share a common behavioural designation or diagnosis.

PMID- 17433443
TI  - Ras/Erk pathway positively regulates Jak1/STAT6 activity and IL-4 gene expression
      in Jurkat T cells.
AB  - T helper cells can be largely divided into two functional subsets, Th1 and Th2,
      which are characterized by the cytokines they produce. The mechanism of Th1
      versus Th2 cytokine production is thought to involve interaction of TCR-induced
      signal and cytokine-induced signal, mainly activating the Ras/MAPK and the
      Jak/STAT pathway, respectively. In order to gain insight into the signal
      transduction network for Th1 and Th2 differentiation, we have analyzed the
      functional cross-talk between the Jak/STAT and the Ras/MAPK pathway. In cytokine
      producing Jurkat T cells, we have found that IL-4 induces activation of Erk and
      Akt, and the IL-4-induced STAT6 activity is suppressed by inhibitors of Erk and
      PI3K. The transfection of daRas into these cells resulted in the up-regulation of
      specific activity of Jak1/STAT6 with a concomitant increase in Erk and Akt
      activity, while siRNA-mediated knock-out of Ras resulted in the inhibition of
      Jak1/STAT6. Furthermore, the IL-4 mRNA expression and IL-4 promoter activity were
      enhanced by daRas but not by dnRas. The Ras-induced increase of both STAT6
      activity and IL-4 mRNA level was effectively blocked by a Mek/Erk inhibitor,
      suggesting that Ras/Erk pathway positively regulates STAT6 activity and IL-4
      transcription. Together, the results indicate that there is a functional cross
      talk between Ras/Erk and IL-4/Jak1/STAT6, which contributes to the regulation of
      IL-4 transcription in T cells.

PMID- 17433444
TI  - Model studies for evaluating the neurobehavioral effects of complex hydrocarbon
      solvents II. Neurobehavioral effects of white spirit in rat and human.
AB  - To evaluate the neurobehavioral effects of hydrocarbon solvents and to establish
      a working model for extrapolating animal test data to humans, studies were
      conducted which involved inhalation exposure of rats and humans to white spirit
      (WS). The specific objectives of these studies were to evaluate the behavioral
      effects of exposure to WS in rats and humans and to determine relationships
      between internal levels of exposure and behavioral effects. In both animals and
      volunteers, methods for assessment of similar functional effects were used to
      enable interspecies comparisons. A battery of tests including standardized
      observational measures, spontaneous motor activity assessments and learned visual
      discrimination performance was utilized in rat studies to evaluate acute central
      nervous system (CNS) depression. Groups of rats were exposed to WS at target
      concentrations of 0, 600, 2400 or 4800mg/m(3), 8h/day for 3 consecutive days.
      Blood and brain concentrations of two WS constituents; 1,2,4-trimethylbenzene
      (TMB) and n-decane (NDEC), were used as biomarkers of internal exposure. In a
      volunteer study, 12 healthy male subjects were exposed for 4h to either 57 or
      570mg/m(3) WS in two test sessions spaced 7 days apart, and neurobehavioral
      effects were measured using a computerized neurobehavioral test battery. Blood
      samples were taken at the end of the exposure period to measure internal
      concentrations of TMB and NDEC. Results of the behavioral tests in rats indicated
      WS-induced changes particularly in performance and learned behavior. In humans,
      some subtle performance deficits were observed, particularly in attention. The
      behavioral effects were related to concentrations of the WS components in the
      central nervous system. These studies demonstrated a qualitative similarity in
      response between rats and humans, adding support to the view that the rodent
      tests can be used to predict levels of response in humans and to assist in
      setting occupational exposure levels for hydrocarbon solvents.

PMID- 17433445
TI  - HPV and circumcision: a biased, inaccurate and misleading meta-analysis.

PMID- 17433446
TI  - Allergic rhinitis and its pharmacology.
AB  - The pathophysiology of allergic rhinitis and its drug treatment is reviewed.
      Special emphasis is placed upon potential new treatments. Allergic rhinitis is
      characterized by allergen(s), symptoms (sneezing, itching, rhinorrhea, nasal
      congestion and nasal hypersensitivity), and signs such as invasion of nasal
      mucosa by inflammatory cells. Such pathological changes are due to inflammatory
      responses mediated by way of allergen-immunoglobulin E (IgE)-cell complex
      formation. The complexity of the disease and the multiple pathways involved offer
      many targets for drug treatment, but to date no single drug is totally effective.
      This review summarizes the current knowledge of allergic rhinitis, its
      prevalence, pathophysiology and experimental and clinical treatments. In the
      search for new drugs, different experimental animal models of allergic rhinitis
      are required. As a result the models have also been reviewed. Furthermore,
      particular aspects of the pathophysiology of allergic rhinitis are discussed in
      greater detail including the immune cells involved in the mediation of the
      disease, chemical mediators, their actions, and the receptors on which they act.
      Therapy, particularly that with current drugs, targets many of the known
      mediators and some of the cellular processes with varying success. Other drugs,
      for example, vasoconstrictors given to reduce rhinorrhea, provide symptomatic
      relief by counteracting symptoms. Since the incidence of allergic rhinitis is
      prevalent and growing in many parts of the world and current treatments are not
      ideal, it is important to continue to study the pharmacology of this disease as
      part of a search for better drugs.

PMID- 17433447
TI  - A reassessment of the role of activity in the formation of eye-specific
      retinogeniculate projections.
AB  - In all mammalian species the projections from the two eyes to the dorsal lateral
      geniculate nucleus of the thalamus terminate in separate layers or territories.
      This mature projection pattern is refined early in development from an initial
      state where the inputs of the two eyes are overlapping. Here I discuss the
      results of studies showing that the formation of segregated eye-specific
      retinogeniculate projections involves activity-mediated binocular competition. I
      conclude that while retinal activity undoubtedly is involved in this process, the
      results of recent studies cast doubt on the prevalent notion that retinal waves
      of activity play an instructional role in the formation of segregated retinal
      projections.

PMID- 17433448
TI  - MALDI-TOF MS of phosphatidylethanolamines: different adducts cause different post
      source decay (PSD) fragment ion spectra.
AB  - Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) is increasingly applied to lipids. However, positional acyl chain
      analysis of lipids by MALDI was so far scarcely described. In this paper, the
      fragmentation behavior of phosphatidylethanolamine (PE) is investigated by using
      post-source decay (PSD) MS. In dependence on the investigated adduct, significant
      differences could be obtained. It will be shown that in particular the negative
      ion spectra enable the determination of the individual acyl chains as well as
      their positions (sn-1 or sn-2). Therefore, MALDI-TOF PSD spectra are a real
      alternative to more sophisticated MS/MS methods.

PMID- 17433449
TI  - A DIGE-based approach to study interacting proteins.
AB  - A full spectrum of high-throughput protein identification and characterization
      approaches has been developed for protein profiling. However, the most demanding
      field to better understanding protein interactions known as the "interactome" is
      still of a perpetual need for modern proteomics. Recently developed DIGE
      (difference in-gel electrophoresis) system may be of potential use when studying
      interacting proteins. In this work we applied DIGE technique on native gel
      electrophoresis to study protein-protein interactions. As a proof of principle,
      we utilized an in vitro interaction model between p53 and HDM2 proteins. In
      parallel, we also showed interaction of these proteins using fluorescently
      labelled p53- or HDM2-immunoprecipitation pellets. Thus, we believe this study
      shows a good potential for investigating various interacting partners and
      benefits towards creation of interactome.

PMID- 17433450
TI  - The potential utility of a staging model as a course specifier: a bipolar
      disorder perspective.
AB  - Staging models are widely used in clinical medicine, and offer an insight into
      the progressive nature of many disorders. In general, the earlier stages of
      illness may be associated with a better prognosis and a higher treatment
      response. Once chronicity is reached, more complex and invasive treatments may be
      required, and the utility of treatments may decline. There is evidence that
      treatment response is greatest in the early phases of the disorder. There is also
      a progressive social and psychological burden of ongoing illness. This is
      paralleled by the twin notions of neuroprotection, which is supported by
      increasing evidence that structural changes in the disorder may be progressive
      and reversible with algorithm appropriate treatment, and that of early
      intervention, which posits that the optimal window for intervention is early in
      the illness course. A staging model compliments existing and proposed
      classifications of bipolar disorder, adding a temporal dimension to a cross
      sectional view. It may inform treatment choice and prognosis, and could have
      utility as a course specifier.

PMID- 17433451
TI  - Myelin staining of deep white matter in the dorsolateral prefrontal cortex in
      schizophrenia, bipolar disorder, and unipolar major depression.
AB  - Neuroimaging and postmortem studies suggest the involvement of white matter
      disease in schizophrenia, bipolar disorder, and unipolar major depression. To
      date there is no published, collective study of myelin staining in these three
      psychiatric disorders. Deep white matter lesions, potentially affecting
      corticolimbic circuits, have been particularly implicated in late life depression
      and poor outcome bipolar disorder. We hypothesized that individuals with these
      disorders would manifest reduced deep white matter myelin staining compared to
      normal controls. Sixty transverse sections of fixed dorsolateral prefrontal
      cortex - 15 from individuals with each psychiatric disorder and 15 from normal
      controls - were stained according to the method of Kluver and Barrera. Myelin
      staining intensity was quantified by digital image analysis and expressed as a
      percent of grey matter staining for a given section. Mean deep (but not gyral)
      white matter myelin staining was less intense in all three psychiatric groups
      compared to control. This difference was statistically significant for the
      bipolar and unipolar groups, with a strong trend toward attenuated staining in
      the schizophrenic group. Our findings are consistent with postmortem and
      neuroimaging studies of affective disorders that indicate an increased prevalence
      of deep white matter lesions in unipolar and bipolar affective disorders.

PMID- 17433452
TI  - Metabotropic glutamate receptors: new targets for the control of tumor growth?
AB  - Cancer stem cells are currently a target for the treatment of malignant tumors.
      Transformed neural stem-progenitor cells of the brain subventricular zone and the
      external granular layer of the cerebellum are the putative cells of origin of
      malignant gliomas and medulloblastomas, which are the most frequent malignant
      brain tumors in adults and children, respectively. The proliferation of neural
      stem-progenitor cells is regulated by metabotropic glutamate (mGlu) receptors,
      which are G-protein-coupled receptors that are activated by glutamate, the major
      excitatory neurotransmitter of the CNS. At least two receptor subtypes - mGlu(3)
      and mGlu(4) receptors - control the proliferation of brain tumor cells, whereas
      mGlu(1) receptors have been implicated in the development of melanomas. We
      believe that individual mGlu receptor subtypes represent new potential targets
      for the treatment of several malignant tumors, including brain tumors.

PMID- 17433453
TI  - Rapid cDNA synthesis and sequencing techniques for the genetic study of
      bluetongue and other dsRNA viruses.
AB  - The genetic study of double-stranded (ds) RNA viruses by sequence analyses of
      full-length genome segments, or entire viral genomes, has been restricted by the
      technical difficulties involved in analyses of dsRNA templates. This paper
      describes improved methods for sequence-independent synthesis of full-length cDNA
      copies of dsRNA genes and associated sequencing strategies. These methods include
      an improved version of the 'Single Primer Amplification Technique' (SPAT -
      [Attoui, H., Billoir, F., Cantaloube, J.F., Biagini, P., de Micco, P. and de
      Lamballerie, X., 2000. Strategies for the sequence determination of viral dsRNA
      genomes. J. Virol. Methods 89, 147-158]), which is described here as 'Full-Length
      Amplification of cDNAs' (FLAC). They also include the development of direct
      sequencing methods (without cloning) for the resulting full-length cDNAs. These
      techniques, which are applicable to any viruses with segmented dsRNA genomes and
      conserved RNA termini, make it possible to generate sequence data rapidly from
      multiple isolates for molecular epidemiology studies.

PMID- 17433454
TI  - Optimization of the virus concentration method using polyethyleneimine-conjugated
      magnetic beads and its application to the detection of human hepatitis A, B and C
      viruses.
AB  - To enhance the sensitivity of virus detection by polymerase chain reaction (PCR)
      and reverse transcription PCR (RT-PCR), a novel virus concentration method using
      polyethyleneimine (PEI)-conjugated magnetic beads was developed in our previous
      study. However, several viruses could not be concentrated by this method. In this
      paper, the conditions of virus concentration were optimized to concentrate a wide
      range of viruses more efficiently. The PEI beads adsorbed viruses more
      efficiently than other cationic polymers, and the optimum virus concentration was
      obtained under weak acidic conditions. Mass spectrometric analysis revealed that
      several serum proteins, such as complement type 3, complement type 4 and
      immunoglobulin M (IgM), were co-adsorbed by the PEI beads, suggesting that the
      beads may adsorb viruses not only by direct adsorption, but also via immune
      complex formation. This hypothesis was confirmed by the result that poliovirus,
      which PEI beads could not adsorb directly, could be concentrated by the beads via
      immune complex formation. On the other hand, hepatitis A (HAV) and hepatitis C
      (HCV) viruses were adsorbed directly by PEI beads almost completely. Like
      poliovirus, hepatitis B virus (HBV) was concentrated efficiently by the addition
      of anti-HBV IgM. In conclusion, virus concentration using PEI beads is a useful
      method to concentrate a wide range of viruses and can be used to enhance the
      sensitivity of detection of HAV, HBV and HCV.

PMID- 17433455
TI  - Comparison of the "ProDect BCS RV CHIP" assay with the combination of shell vial
      cell culture and immunofluorescence antibody test for the detection of
      respiratory viruses.
AB  - In the present study, a multiplex reverse transcriptase polymerase chain reaction
      combined with a chip hybridization assay (ProDect BCS RV CHIP) was evaluated as
      an alternative to the combination of immunofluorescent antibody test and shell
      vial cell culture considered as gold standard for the detection of respiratory
      viruses. Among 100 specimens, 40 were positive using the combination of
      immunofluorescent antibody test and shell vial cell culture assay in which 9 of
      them were infected by two different viruses (27 parainfluenza virus type 3, 10
      adenovirus, 9 respiratory syncytial virus, 2 influenza type B, and 1 influenza
      type A). ProDect BCS RV CHIP detected only 10 positive specimens in which one of
      them was infected by two different viruses (5 respiratory syncytial virus, 3
      parainfluenza virus type 3, 2 adenovirus, and 1 influenza virus type B). The
      sensitivity, specificity, PPV, NPV, and diagnostic accuracy of ProDect BCS RV
      CHIP were 25.0%, 100%, 100%, 66.6%, and 70.0%, respectively, compared to the
      combination of shell vial cell culture and immunofluorescent antibody test. As a
      result, the specificity of ProDect BCS RV CHIP is high, however, the sensitivity
      (25%) of the assay is not sufficient for routine laboratory use.

PMID- 17433456
TI  - The rate of behavioral tolerance development to repeated lipopolysaccharide
      treatments depends upon the time of injection during the light-dark cycle: a
      multivariable examination of locomotor activity.
AB  - Recent evidence suggests that sickness behaviors following lipopolysaccharide
      (LPS)-treatment may be modulated by environmental factors such as the light-dark
      (LD) cycle. The present study characterized LPS-induced hypoactivity and
      behavioral tolerance development across individual phases of the light-dark cycle
      and the transitions between phases. On days 1, 4 and 7, male rats were treated
      with LPS (200microg/kg i.p.) or saline 30min prior to the onset of either the
      dark period (dark-tested group) or the light period (light-tested group).
      Following treatment, rats were placed in non-novel automated open-fields where
      various aspects of locomotor activity were monitored for 16h. On day 1, LPS
      treated rats in both the dark and light tested groups showed significant
      hypoactivity. However, temporal differences in the onset of hypoactivity were
      observed between the groups. In dark tested animals significant hypoactivity
      started 60min after LPS treatment and continued until the light period when
      hypoactivity was diminished. In contrast, the light tested LPS-treated animals
      did not exhibit a prolonged period of hypoactivity until the transition between
      the light and dark periods, 750min following LPS injection. On days 4 and 7,
      light tested animals showed complete tolerance to LPS as evidenced by the absence
      of significant activity reductions, whereas dark tested animals continued to show
      significant periods of hypoactivity. These results indicate that there are day
      night differences in both the initial LPS-induced hypoactivity response as well
      as behavioral tolerance development. The rate of tolerance development to LPS may
      be a critical factor to survival and the prevention of sepsis, as organisms are
      repeatedly exposed to pathogens across the life cycle.

PMID- 17433457
TI  - Effect of the water-soluble fraction of petroleum on microsomal lipid metabolism
      of Macrobrachium borellii (Arthropoda: Crustacea).
AB  - The effect of the water-soluble fraction of crude oil (WSF) on lipid metabolism
      was studied at critical metabolic points, namely fatty acid activation, enzymes
      of triacylglycerol and phospholipid synthesis, and membrane (lipid packing)
      properties in the freshwater prawn Macrobrachium borellii. To determine the
      effect of the contaminant, adults and embryos at different stages of development
      were exposed to a sublethal concentration of WSF for 7 days. After exposure,
      microsomal palmitoyl-CoA synthetase (ACS) showed a two-fold increase in adult
      midgut gland. Embryo's ACS activity was also affected, the increment being
      correlated with the developing stage. Endoplasmic reticulum acylglycerol
      synthesis was also increased by WSF exposure in adults and stage 5 embryos, but
      not at earlier stages of development. Triacylglycerol synthesis was particularly
      increased (18.5%) in adult midgut gland. The microsomal membrane properties were
      studied by fluorescent steady-state anisotropy, using the rotational behavior of
      the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH). Microsomes from midgut
      gland of WSF-exposed prawn showed no differences in fluidity. Nevertheless,
      microsomes incubated with WSF in vitro increased their fluidity in a temperature-
      and WSF concentration-dependent fashion. Both, aliphatic and aromatic
      hydrocarbons individually tested elicited an increase in membrane fluidity at 10
      mg/l, but at 4 mg/l only nC10-C16 aliphatics did. In vivo results indicate that
      WSF increased the activity of microsomal enzymes that are critical in lipid
      metabolism, though this change was not due to direct alterations in membrane
      fluidity, suggesting a synthesis induction, or an enzyme-regulatory mechanism.
      Nevertheless, hydrocarbons elicited membrane fluidity alterations in in vitro
      experiments at concentrations that could be found in the environment after an oil
      spill.

PMID- 17433458
TI  - The effects of copper and benzo[a]pyrene on retinoids and reproduction in
      zebrafish.
AB  - This study examines whether a link exists between toxicant exposure, retinoids
      and reproduction in fish. Zebrafish were fed a control diet (8.1 microg Cu/g
      diet, 0 microg benzo[a]pyrene/g diet) or diets containing elevated copper (100
      microg, 500 microg and 1000 microg Cu/g diet) or benzo[a]pyrene (B[a]P; 30 and
      150 microg B[a]P/g diet) for 260 days. Toxicant-supplemented diets did not affect
      growth or mortality rates. While whole body retinoid levels in control zebrafish
      decreased during the experiment, females exposed to Cu or B[a]P for 200 days or
      more experienced additional losses of retinyl esters (45-100% depleted) and
      retinal (45% depleted in B[a]P-fed fish). Despite the reduced retinoids, Cu and
      B[a]P did not effect reproduction with respect to the number of eggs spawned,
      fertilization rates or egg retinal content (retinal was instead increased 55-65%
      in eggs from B[a]P-fed fish). There were no apparent deformities observed in 36 h
      post fertilization embryos from any treatment. It appears that although internal
      retinoid stores were depleted in adults, dietary retinoids were sufficient to
      meet the daily requirement for retinal deposition in the eggs and retinoic acid
      synthesis. This study has shown that retinoid levels in female zebrafish are
      sensitive to Cu and B[a]P, and are a good indicator of long-term exposure. It
      also brings to light the resiliency of the retinoid system in fish and the
      importance of the diet on the toxicological response. Specifically that dietary
      retinoids appear to support normal reproduction in the absence of internal
      retinoid stores.

PMID- 17433459
TI  - The effect of maternal exposure to contaminated sediment on the growth and
      condition of larval Fundulus heteroclitus.
AB  - We employed a factorial laboratory experiment to determine the single and
      combined effect of maternal and larval exposure to contaminated sediment from
      Elizabeth River, Virginia, a site contaminated with high concentrations of
      multiple pollutants. Females were exposed to either reference or contaminated
      sediment and the larvae from both groups of mothers were in turn transferred to
      either reference or contaminated sediment. We found a strong maternal influence
      on yolk area, length and RNA:DNA ratio at hatch. Further, the maternal exposure
      significantly influenced growth rate and RNA:DNA ratios of larvae 14 days after
      hatch and was a more important factor in determining these endpoints than larval
      exposure. We found that after 14 days larvae were larger and had higher
      survivorship when the maternal and larval exposures were the same. There also was
      no statistical difference with respect to growth and condition between larvae
      that had hatched from exposed mothers and remained in contaminated water and
      larvae that had hatched from reference mothers and were placed in either
      reference or contaminated sediment. However, larvae that hatched from exposed
      mothers and then were switched to reference sediment had significantly lower
      growth, lower RNA:DNA ratios, and were smaller despite being large at hatch size,
      indicating that there are fitness trade-offs in exchange for apparent resistance
      to contaminants which are provided by the mother. Maternal effects add complexity
      to ecotoxicological research and should be incorporated into studies to predict
      population level responses more realistically.

PMID- 17433460
TI  - Regions in the 3' untranslated region confer stage-specific expression to the
      Leishmania mexicana a600-4 gene.
AB  - Protozoan parasites of the genus Leishmania have a digenetic lifecycle,
      alternating between the promastigote and amastigote stages. The extracellular
      promastigote resides within a sandfly vector, while the obligate intracellular
      amastigote stage replicates in the phagolysosome of mammalian host macrophages.
      Adaptation to and survival within these vastly differently environments is
      accompanied by differential expression of a subset of genes, which is regulated
      post-transcriptionally via cis-acting elements in 3' untranslated region (3'UTR)
      or intercistronic sequences. It was reported previously that Leishmania mexicana
      A600-4 mRNA transcript abundance was eight-fold higher in the amastigotes. In
      this study, chimeric luciferase:A600-4 3'UTR reporter constructs were integrated
      at the A600 chromosome locus to identify regulatory regions of the A600-4 3'UTR
      sequence. Evidence is provided for distinct 3'UTR elements that function to
      stabilize the A600-4 mRNA transcript in the amastigote stage and to regulate
      translation efficiency, respectively.

PMID- 17433461
TI  - Role of extracellular charged amino acids in the yeast alpha-factor receptor.
AB  - The yeast pheromone receptor, Ste2p, is a G protein coupled receptor that
      initiates cellular responses to alpha-mating pheromone, a 13 residue peptide that
      carries a net positive charge at physiological pH. We have examined the role of
      extracellular charged groups on the receptor in response to the pheromone.
      Substitutions of Asn or Ala for one extracellular residue, Asp275, affected both
      pheromone binding and signaling, suggesting that this position interacts directly
      with ligand. The other seven extracellular acidic residues could be individually
      replaced by polar residues with no detectable effects on receptor function.
      However, substitution of Ala for each of these seven residues resulted in
      impairment of signaling without affecting pheromone binding, implying that the
      polar nature of these residues promotes receptor activation. In contrast,
      substitution of Ala for each of the six positively charged residues at the
      extracellular surface of Ste2p did not affect signaling.

PMID- 17433462
TI  - Assessing selected quality of life factors of nursing home residents in Turkey.
AB  - As a result of improved public health and medical advances, not only has life
      expectancy among older people increased, but the importance of quality of life in
      terms of health in later life has also increased. The aim of this study was to
      investigate the relationship between socio-demographic factors, health-related
      behaviors, residents' satisfaction, and functional disability levels among
      elderly people living in nursing homes in Turkey using the World Health
      Organization's Quality of Life-BREF (WHOQOL-BREF). Data regarding socio
      demographic characteristics, chronic health problems, health-related behaviors
      (smoking, alcohol consumption, physical activity, etc.) were collected from the
      study group (N=107) by a structured questionnaire during face-to-face interviews.
      Dependencies in activities of daily living (ADL) of the study group were also
      assessed using Katz's ADL index. The mean WHOQOL-BREF scores were significantly
      higher in participants who had independence in performing ADL (bathing, dressing,
      toileting, transfer, continence, feeding) (p<0.0001, p<0.0001, p<0.0001, p<0.001,
      p<0.0001, and p<0.001, respectively). It was found that WHOQOL-BREF scores were
      positively associated with having physical exercise habits and residents'
      satisfaction with nursing homes; being dependent in dressing were significant
      predictors of in the study (R(2): 0.38, p<0.003, p<0.0001, and p<0.0001,
      respectively). Residents' satisfaction from living nursing homes and
      participation in physical exercise were significant predictors of WHOQOL-BREF
      scores for those that participated in this study.

PMID- 17433463
TI  - Emergency coronary artery bypass grafting in patients with acute myocardial
      infarction treated with glycoprotein IIb/IIIa receptor inhibitors.
AB  - Glycoprotein (GP) IIb/IIIa receptor inhibitors before primary angioplasty in
      patients with ST-elevation acute myocardial infarction (STEMI) are recommended by
      current guidelines. Thus, an increasing number of patients receive these drugs
      before coronary angiography, particularly if a between-hospital transfer is
      needed. However, when coronary anatomy is unsuitable for angioplasty, emergency
      coronary artery bypass grafting (CABG) under GP IIb/IIIa inhibitor treatment may
      be needed, with a potential increase in bleeding risk. Abciximab has a long
      duration of action, because of its high-affinity binding to GP IIb/IIIa
      receptors. Initial retrospective studies reported a higher incidence of major
      bleeding during emergency CABG after abciximab administration, leading to the
      recommendation of delaying surgery >12 h. However, data from the prospective
      trials on abciximab do not confirm the increase in bleeding risk, and current
      evidence shows that emergency surgery can be performed safely soon after
      abciximab cessation. Monitoring of activated clotting time during surgery and
      platelet transfusion in case of postoperative relevant bleeding are the only
      measures needed. No data are available on emergency surgery in patients with
      STEMI treated with eptifibatide or tirofiban. However, their short-lasting
      effects and the results of trials on non-ST-elevation acute coronary syndromes
      suggest that they could even reduce postoperative bleeding by preventing platelet
      consumption during cardiopulmonary bypass. In conclusion, the early
      administration of GP IIb/IIIa inhibitors, in particular of abciximab, in patients
      with STEMI in whom primary angioplasty is planned should not be discouraged
      because of the potential bleeding risk in case of emergency CABG.

PMID- 17433465
TI  - The beneficial effect of biventricular pacing on ventricular tachycardia in a
      patient with non-ischemic cardiomyopathy.
AB  - The effect of cardiac resynchronisation therapy on ventricular tachycardias (VT)
      has not been well established. This case-report demonstrates the favourable
      impact of biventricular pacing on ventricular arrhythmias. In 2004, a patient
      with dilated cardiomyopathy and ICD since 1999 was admitted to our Division for
      multiple VT. While left ventricular function was markedly reduced and mitral
      regurgitation was severe, he was asymptomatic for heart failure. Amiodarone was
      not administered on account of a documented proarrhythmic effect. The patient's
      ICD was upgraded to an ICD-biventricular system. After upgrading, a significant
      reduction in the number of VT was noted.

PMID- 17433464
TI  - Pulmonary valve replacement in tetralogy of Fallot improves the repolarization.
AB  - OBJECTIVE: To assess the effect of pulmonary valve replacement (PVR) on the
      repolarization of patients with tetralogy of Fallot. BACKGROUND: Pulmonary valve
      regurgitation may cause right ventricular failure in adult patients with Fallot's
      tetralogy. In these patients, prolonged depolarization and disturbed
      repolarization are associated with ventricular arrhythmias and sudden cardiac
      death. METHODS: Thirty Fallot patients (age 32+/-9 years, 19 male) eligible for
      PVR were studied with cardiac magnetic resonance imaging (CMR) before and 6
      months after PVR. Electrocardiograms obtained during initial and follow-up CMR
      were analyzed and occurrence of ventricular arrhythmias was studied. RESULTS:
      Right ventricular end-diastolic volume (RV EDV) decreased from 322+/-87 to 215+/
      57 ml after PVR (P<0.0001). The spatial QRS-T angle normalized from 117+/-34 to
      100+/-35 degrees , P=0.0004 (normal angle <105 degrees). QT dispersion and T-wave
      complexity did not change significantly. T-wave amplitude decreased from 376+/
      121 to 329+/-100 microV (P=0.01). T-wave area decreased from 43+/-15 to 38+/-13
      microV s (P=0.02). Decreases in T-wave amplitude and area were most prominent in
      the right precordial leads overlying the RV. Three patients had sustained
      ventricular arrhythmias and one patient died suddenly. These patients had a QRS
      duration >160 ms. No severe ventricular arrhythmias were found in patients with a
      RV EDV <220 ml, QRS-T angle <100 degrees , QT dispersion <60 ms or T-wave
      complexity <0.30. CONCLUSION: Normal repolarization indices may be associated
      with the absence of severe ventricular arrhythmias. PVR in Fallot patients with
      dilated right ventricles has a beneficial effect on electrocardiographic indices
      of repolarization heterogeneity.

PMID- 17433466
TI  - Improvement of left ventricular mechanical dyssynchrony associated with
      restoration of left ventricular function in a patient with fulminant myocarditis
      and complete left bundle branch block.
AB  - A 52-year-old woman with fulminant myocarditis had completed left bundle branch
      block (LBBB) and severely impaired left ventricular (LV) function. Marked
      mechanical dyssynchrony with septal-to-posterior delay of 389 ms was observed by
      echocardiographic speckle tracking radial strain imaging on admission, which was
      dramatically improved to 106 ms after total recovery from acute myocarditis with
      restoration of LV ejection fraction whereas her electrocardiogram still showed
      complete LBBB.

PMID- 17433467
TI  - The His family and their contributions to cardiology.
AB  - Few families in medicine can claim that more than one of their members
      contributed significantly to modern-day clinical and research practices. The
      Swiss family of His can assert that two of their number, Wilhelm His Sr. (1831
      1904) and Wilhelm His Jr. (1863-1934) made advancements in medicine that still
      have an impact on many areas of research and clinical practice today. In 1865,
      His focused on embryology research and he introduced the term "endothelium" from
      his observations in embryology. His invented the microtome in 1866, and named the
      axonal appendages as dendrites. On the other hand His Jr., in 1893, published a
      35-page article that described the activity of the embryonic heart and how this
      understanding is important in comprehending actions in the adult heart. This
      article contains the description of his best-known discovery, the now eponymous
      Bundle of His. Modern researchers and clinicians should consider the importance
      of the work of both Wilhelm His Sr. and Wilhelm His Jr. Advancements in
      embryological, histological and cardiovascular electrophysiology research can all
      trace some input back to this father and son.

PMID- 17433468
TI  - Patency of infarct related artery after pharmacological reperfusion during
      transfer to primary percutaneous coronary intervention influences left
      ventricular function and one-year clinical outcome.
AB  - BACKGROUND: Time-to-treatment is an important determinant of mortality in primary
      angioplasty for ST-segment elevation myocardial infarction (STEMI). Thus, the
      benefits in outcome observed with transferring for primary angioplasty in
      comparison with on-site thrombolysis may be reduced or even lost when long
      distance transportation is required. Even though pharmacological reperfusion
      might overcome this limitation, no data have been reported so far on the
      prognostic role of early pharmacological recanalization in STEMI patients
      undergoing long-distance transportation for primary angioplasty. METHODS: We
      enrolled 225 consecutive STEMI patients without shock, eligible for thrombolysis,
      with at least 90-minute transport time to our primary PCI center. During
      transport, patients received i.v. heparin 40 U/kg, alteplase 15 mg+35 mg infusion
      and abciximab 0.25 mg/kg+0.125 microg/kg/min infusion for 12 h. RESULTS: Patients
      were divided into two groups according baseline angiography, which showed early
      pharmacological reperfusion (preprocedural TIMI flow 2+3) in 193 patients (85.8%)
      and no reperfusion (preprocedural TIMI flow 0+1) in 32 patients (14.2%). Despite
      no difference in postprocedural TIMI flow, early reperfusion was associated with
      better postprocedural myocardial perfusion (TMPG 3: 54.9% vs. 18.7%, p<0.0001),
      better improvement in left ventricular ejection fraction (LVEF) (from 55.6+/-8.6%
      to 58.8+/-10.4% p<0.001 with early reperfusion vs. 52.9+/-13.4% to 50.4+/-15.8%
      with no early reperfusion, p=NS) and 1-year outcome (p=0.002 log rank). In
      multivariate analysis, preprocedural TIMI flow 0+1 independently predicted death
      and reinfarction at 1 year, and lack of LVEF improvement at 6 months.
      CONCLUSIONS: Early pharmacological reperfusion in STEMI patients undergoing long
      distance transportation for primary angioplasty is associated with better
      postprocedural myocardial perfusion, better LVEF recovery at 6 months and
      improved 1-year clinical outcome.

PMID- 17433469
TI  - Further inflammatory information on metabolic syndrome by adiponectin evaluation.
AB  - BACKGROUND: Despite a close association of adiponectin with metabolic syndrome
      (MetS), its usefulness as an additional MetS factor has not been well
      investigated. METHODS: We studied 2327 apparently healthy Japanese male office
      workers aged 35 to 66 years old and investigated cross-sectionally whether
      categorization by serum adiponectin distinguished participants' levels of high
      sensitivity C-reactive protein (CRP) beyond the conventional MetS. RESULTS: In a
      linear regression analysis, adiponectin was associated with CRP independently of
      all MetS factors (beta=-0.192, P<0.001). Furthermore, a graded decrease in CRP
      level was observed with elevation of adiponectin in every stratum characterized
      by the presence or absence of each MetS component (trend P<0.05 in all strata
      except those of decreased high-density lipoprotein cholesterol or hyperglycemia).
      Similarly, geometric means of CRP levels (mg/l) decreased as adiponectin
      increased from the lowest to the highest tertile in all strata classified by the
      number of MetS components, though a P value did not reach statistical
      significance in those with 3 MetS components (the stratum of 0 MetS component:
      0.41 [95% confidence interval, 0.34-0.49], 0.32 [0.28-0.37] and 0.26 [0.23-0.30],
      trend P<0.001; 1 component: 0.45 [0.39-0.52], 0.38 [0.34-0.43], and 0.32 [0.28
      0.36], trend P<0.001; 2 components: 0.58 [0.50-0.67], 0.51 [0.44-0.60], and 0.46
      [0.38-0.55], trend P=0.043; 3 components: 0.80 [0.66-0.96], 0.69 [0.55-0.87], and
      0.58 [0.39-0.85], trend P=0.139). CONCLUSIONS: Adiponectin evaluation provides
      additional inflammatory information on conventional MetS, supporting the
      potential of hypoadiponectinemia as an additional MetS component for identifying
      high-risk individuals for cardiovascular disease.

PMID- 17433470
TI  - Changes during exercise of ECG intervals related to increased risk for
      ventricular arrhythmia in repaired tetralogy of Fallot and their relationship to
      right ventricular size and function.
AB  - PURPOSE: Our study aimed to assess pro-arrhythmogenic electrocardiographic
      changes during maximal physical exercise in patients operated for Tetralogy of
      Fallot (TOF). METHODS: TOF patients prospectively underwent: 1) bicycle
      ergometry, 2) cardiac MRI, and 3) 24-hour Holter. ECG data was analyzed at rest,
      at 60% of peak exercise and at peak exercise. R-R duration, QRS-, QT- and JT
      duration and dispersions were assessed. Changes of ECG parameters during exercise
      were calculated and correlated to RV volume, RVEF, RV wall-mass, PR-percentage
      and VO(2max). Exercise ECG data from healthy controls were used as reference.
      RESULTS: Thirty-one patients (mean age at repair (SD) 0.8 (0.5) years, age at
      study 16 (5) years) and 25 controls (age 12 (2) years) were included. With
      exercise mean QTc and JTc dispersions increased in patients (p<0.001), but not in
      controls. At peak exercise JTc dispersion was larger in patients (p<0.01). QTc
      did not change with exercise in patients (p=0.14) and decreased in controls
      (p<0.05). At all levels of exercise mean QTc, QRS and QRS dispersion were larger
      in patients (all p<0.001). Significant associations were found for; 1) a larger
      increase of JTc dispersion with a higher PR-percentage, a larger RV volume, a
      larger RV wall-mass, 2) a larger QTc increase with a larger RV volume and worse
      RVEF. CONCLUSION: During physical exercise inhomogeneity of repolarisation, known
      to predispose for re-entry ventricular arrhythmia, increases in repaired TOF.
      Larger inhomogeneity is found with more severe PR.

PMID- 17433471
TI  - Are we misunderstanding beta-blockers.
AB  - In myocardial ischaemia and heart failure, beta-blockers with intrinsic
      sympathomimetic activity (ISA) e.g. pindolol, xamoterol, bucindolol, nebivolol,
      have performed poorly in reducing morbidity and mortality. In both indications
      beta-1 blockade is the vital active ingredient. Beta-1 blockade (bisoprolol) is
      now an alternative first-line choice to Ace-inhibition in the treatment of heart
      failure. The therapeutic role of beta-blockers in hypertension is less well
      understood, particularly since the new recommendations in the UK from the NICE
      committee stating that: 1. beta-blockers are no longer preferred as a routine
      initial therapy, 2. the combination with diuretics is discouraged due to the risk
      of induced diabetes, and 3. in younger patients first-choice initial therapy
      should be an ACE-inhibitor. Recent data from the Framingham Heart Study and other
      epidemiological studies have indicated that the development of diastolic
      hypertension in younger subjects is closely linked to weight-increase and an
      increase in peripheral resistance; such subjects have a high adrenergic drive and
      cardiac output. In contrast, elderly systolic hypertension mostly arises de novo
      via poor vascular compliance. Thus in younger, probably overweight, hypertensives
      (including diabetics) first-line beta-blockade has performed well in preventing
      myocardial infarction (a fact hidden by meta-analyses that do not take age into
      account). Conversely, in elderly hypertensives first-line beta-blockade
      (atenolol) has performed poorly in reducing cardiovascular risk (due to partial
      beta-2 blockade atenolol evokes metabolic disturbance and does not improve
      vascular compliance, or effectively lower central aortic pressure or reverse left
      ventricular hypertrophy). Thus beta-blockers like atenolol are ill-equipped for
      first-line therapy in elderly hypertension. Some beta-blockers, e.g. bisoprolol
      (up to 10 mg/day is highly beta-1 selective) and nebivolol (beta-2/3 intrinsic
      sympathomimetic activity), do improve vascular compliance and cause no metabolic
      disturbance. Beta-blockers as second-line to low-dose diuretics (which, by
      improving vascular compliance and increasing sympathetic nerve activity, create
      an optimal environment for beta-blockade) in elderly hypertension (including
      diabetics) have performed well in reducing cardiovascular events (this
      combination has the added bonus of reducing the risk of bone fracture by about
      30%). Meta-analyses which include studies where it is unclear whether a diuretic
      or beta-blocker was a first-line therapy will dilute the benefit stemming from
      first-line diuretic/second-line beta-blockade. Hypertensives (of all ages) with
      ischaemia are well suited to beta-blockade.

PMID- 17433472
TI  - Long-term behavioural and emotional problems in four cardiac diagnostic groups of
      children and adolescents after invasive treatment for congenital heart disease.
AB  - AIMS: To assess the occurrence of a wide range of behavioural and emotional
      problems long-term after invasive treatment for congenital heart disease (ConHD)
      in infancy and childhood. METHODS: Parents of 125 ConHD children, aged 7-17,
      completed the Child Behavior Checklist and 85, 11-17-year-old, ConHD children
      completed the Youth Self-Report. RESULTS: According to parents' reports of
      problem behaviours a significant proportion of ConHD children scored in the
      deviant range (16.9%) compared to the reference group (10.2%). The proportion of
      ConHD boys scoring in the deviant range according to parents (21.4%) was
      significantly greater than that in the reference sample (10%). Parents reported
      significantly higher problems scores for the scales Somatic Complaints, Social
      Problems, Attention Problems, Internalising and Total Problems compared to the
      reference group. In contrast, reports of patients were comparable to those of
      reference peers. No differences were found on the self-reports between problem
      scores for different cardiac diagnostic groups. Discrepancies between self- and
      parent-reports were found, indicating that more problems were reported by ConHD
      patients themselves than by their parents. CONCLUSION: Overall, parents of ConHD
      patients reported higher levels of behavioural and emotional problems compared to
      the reference group whereas patients themselves reported no long-term behavioural
      impairment compared to same-sex reference peers. Assessing behavioural and
      emotional problems in ConHD patients can be helpful to detect children at risk
      for developing psychopathology. Especially younger male ConHD patients deserve
      special attention.

PMID- 17433473
TI  - BNP cannot replace gated equilibrium radionuclide ventriculography in monitoring
      of anthracycline-induced cardiotoxity.
AB  - BACKGROUND: Cardiotoxity is a side-effect of cancer treatment with anthracycline
      that is currently monitored by measuring the left ventricular ejection fraction
      (LVEF) by gated equilibrium radionuclide ventriculography (RNV). We hypothesized
      that BNP measurements could replace, at least in part, the RNV examinations.
      Therefore, we studied whether BNP could be used, alone or in combination with
      RNV, in the monitoring of anthracycline-induced cardiotoxity. METHODS: A total of
      333 patients undergoing anthracycline treatment had LVEF and BNP concentration
      measured. Of these, 73 had more than one determination. In the 333 patients we
      compared the BNP concentration to LVEF, and further, for the 73 patient with more
      than one examination, we compared the changes in LVEF and BNP. We evaluated
      different BNP cut-off values for detection of LVEF below 0.50, 0.45 and 0.40,
      respectively. RESULTS: Using LVEF below 0.50 and a BNP cut-off value of 100 pg
      ml(-1) it was possible to save 90% of the RNV determinations with the cost of
      overlooking 68% of the patients with reduced LVEF. Using LVEF below 0.45 and a
      BNP cut-off value of 30 pg ml(-1) it was possible to save 59% of the RNV
      determination, with the cost of overlooking 15% of the patients with reduced
      LVEF. CONCLUSION: BNP cannot safely be used as an alternative to RNV
      determination of LVEF in patient undergoing anthracycline treatment if the
      standard limit of an LVEF of 0.50 was used. However, if only lower LVEF were to
      be detected BNP could be used to save RNV determinations.

PMID- 17433474
TI  - Prognostic impact of pulmonary arterial hypertension: a population-based
      analysis.
AB  - BACKGROUND: Although pulmonary arterial hypertension (PAH) is widely accepted as
      deadly, if not a rare disease, its prognostic impact beyond reports from
      specialist centres is unknown. METHODS: Using the unique Scottish Morbidity
      Record Scheme and linked survival data, we tracked the survival of all Scottish
      adults aged < or =65 years admitted for the first time during the period of 1986
      to 2001 with a probable diagnosis of Idiopathic PAH and a PAH related to
      connective tissue disorders (Connective PAH) and congenital abnormalities
      (Congenital PAH) - the three most common forms of PAH. RESULTS: Overall, 374
      Scottish men and women were discharged from the hospital with incident PAH during
      the period 1986 to 2001. On an unadjusted basis, Congenital PAH (40-45%) was
      associated with the lowest case fatality at 5 years in both men and women. In
      both sexes, Idiopathic PAH and Connective PAH were associated with high initial
      one-year case fatality (20-30%) with a steady accumulation of fatal events in the
      four years thereafter (60-75% case fatality at 5 years). Overall, the adjusted
      risk of dying within one year in the period 1986 to 1989 was 2.22-fold greater
      (OR 95% CI, 1.27 to 3.85) than in 1998 to 2001 (P<0.001). The greatest falls in
      one year case fatality were seen in those with Connective PAH (18-fold increased
      risk of dying in 1986 to 1989 versus 1998 to 2001: P=0.013). Similarly, women
      (adjusted OR 1.38, 95% CI 1.16 to 1.63: P<0.001) and the most deprived
      individuals (OR 2.38, 95% CI 1.17 to 4.82: P<0.05) were at greater risk of dying
      within 5 years. Alternatively, those patients discharged in 1997 were less likely
      to die during this period compared to their 1986 counterparts, although this
      difference did not quite reach statistical significance (OR 0.45, 95% CI 0.22 to
      1.06: P=0.056). CONCLUSION: This population-based study has confirmed the deadly
      impact of the three most common forms of PAH. Overall, there are encouraging
      trends in relation to one and five year adjusted survival rates; particularly in
      relation to PAH related to connective tissue disorders.

PMID- 17433476
TI  - Epidemic of overweight and obesity in Latin America and the Caribbean.

PMID- 17433475
TI  - Apolipoprotein E gene epsilon2/epsilon3/epsilon4 polymorphism and myocardial
      infarction: case-control study in a large population sample.
AB  - It has not been clearly established yet whether the epsilon2/epsilon3/epsilon4
      polymorphism of the gene encoding apolipoprotein E is associated with myocardial
      infarction. We addressed this issue in a large case-control sample and found no
      statistically significant relationship between the epsilon2/epsilon3/epsilon4
      polymorphism and myocardial infarction. The epsilon2 allele and epsilon2epsilon3
      genotype showed trends towards lower risks of myocardial infarction than the
      epsilon3epsilon3 genotype.

PMID- 17433477
TI  - The impact of circulating total homocysteine levels on long-term cardiovascular
      mortality in patients with acute coronary syndromes.
AB  - BACKGROUND: To evaluate the possible independent impact of circulating total
      homocysteine (tHcy) levels on long-term cardiovascular mortality, in patients
      with either ST-segment elevation myocardial infarction (STEMI), or non-ST-segment
      elevation acute coronary syndromes (NSTE-ACS). METHODS: A total of 458 STEMI and
      476 NSTE-ACS patients who presented consecutively, within the first 12 and 24 h
      of index pain respectively were studied. Each cohort was divided according to
      tertiles of circulating tHcy levels upon presentation. Early (30 days) and late
      (31 days through 5 years) cardiovascular mortality was the predefined study
      endpoint. RESULTS: There was no difference in the risk of 30-day cardiovascular
      death among the tertiles of tHcy in patients with STEMI (7.2%, 8.5% and 12.4% for
      the first, second and third tertiles respectively; p(trend)=0.3) or NSTE-ACS
      (3.1%, 3.8% and 5.7% for the first, second and third tertiles respectively;
      p(trend)=0.5). Patients in the upper tHcy tertile were at significantly higher
      unadjusted risk of late (from 31 days trough 5 years) cardiovascular death than
      those in the other two tertiles in STEMI (23.4%, 27.9% and 41.8% for the first,
      second and third tertiles respectively; p(trend) <0.001), and NSTE-ACS (24.7%,
      28.1% and 45.6% for the first, second and third tertiles respectively; p(trend)
      <0.001) cohorts. However, after adjustment for baseline differences, there was no
      significant difference in the risk of late cardiovascular death among tHcy
      tertiles in either cohort. When circulating tHcy levels were treated as a
      continuous variable, they were significantly associated with late cardiovascular
      death (p<0.001 for both cohorts) by univariate Cox regression analysis, but not
      by multivariate Cox regression analysis (p=0.8, and p=1 for STEMI and NSTE-ACS
      cohorts, respectively). CONCLUSIONS: Based on the present data circulating tHcy
      levels determined upon admission do not serve as an independent predictor of long
      term cardiovascular mortality in patients with either STEMI or NSTE-ACS.

PMID- 17433478
TI  - Combined complex open heart surgery and infra-renal aortic aneurysm repair.
AB  - The optimal management of patients with combined ischemic and/or valvular heart
      disease and abdominal aortic aneurysm is still a matter of debate. A 60-year-old
      woman presented with a large infra-renal aortic aneurysm. Preoperative workup
      revealed ischemic cardiomyopathy and aortic regurgitation. She was submitted to
      one-stage aneurysm repair and complex heart surgery. Postoperatively, she
      developed mediastinal bleeding, transient renal dysfunction, pulmonary edema and
      superficial wound infection. She was discharged home about a month later without
      residual problems.

PMID- 17433479
TI  - Serological evidence of early remodeling in high-risk non-ST elevation acute
      coronary syndromes.
AB  - INTRODUCTION: Non-ST elevation acute coronary syndrome (ACS) represents a
      spectrum of risk, with electrocardiographic (ECG) changes and a positive troponin
      being associated with higher morbidity and mortality. Ischaemia produces
      alterations in the collagenous component of the heart, even in the absence of
      myocyte necrosis. Collagen turnover can be assessed biochemically with C
      propeptide for type I collagen (PICP) and C-telopeptide for type I collagen
      (CITP) being markers of collagen synthesis and degradation respectively. Tissue
      inhibitor of matrix metalloproteinase-1 (TIMP-1) is a marker of inhibition of
      degradation. METHODS: Fifty-two patients with non-ST elevation acute ACS were
      recruited and dichotomised into high- and low-risk groups based on ECG and
      troponin level. Sequential measurements of plasma PICP, CITP and TIMP-1 were
      performed over a 48 hour period. RESULTS: Twenty were classified as low-risk
      (negative troponin and normal ECG) and 32 as high-risk. PICP was within the
      normal range at all time points in both groups. However, admission CITP was
      higher in the high-risk group (3.7 vs. 2.6 ng/ml, p<0.001) and, unlike the low
      risk group, demonstrated a further rise over 48 h. Similarly, mean TIMP-1
      displayed a sequential change over time in the high-risk group only, and
      admission level was higher compared to the low-risk group (302 vs. 221 ng/ml,
      p<0.01). DISCUSSION: There is serological evidence of time-dependent altered
      collagen metabolism in high-risk ACS, which is not present in the low-risk group.
      This may reflect a degree of remodeling and may aid risk stratification of
      patients presenting with non-ST elevation ACS.

PMID- 17433480
TI  - Development of a rapid quantitative PCR assay for direct detection and
      quantification of culturable and non-culturable Escherichia coli from agriculture
      watersheds.
AB  - A real-time quantitative polymerase chain reaction (Q-PCR) assay was developed
      for detecting and quantifying Escherichia coli in water samples from agricultural
      watersheds. The assay included optimization of DNA extraction and purification
      from water samples, and Q-PCR amplification conditions using newly designed
      species-specific oligonucleotide primers derived from conserved flanking regions
      of the 16S rRNA gene, the internal transcribed spacer region (ITS) and the 23S
      rRNA gene. The assay was optimized using a pure culture of E. coli with known
      quantities spiked into autoclaved agricultural water samples. The optimized assay
      was capable of a minimum quantification limit of 10 cells/ml of E. coli in the
      spiked agricultural water samples. A total of 121 surface water samples from
      three agricultural watersheds across Canada were analyzed, and results were
      compared with conventional culture-based enumerations of E. coli. The Q-PCR assay
      revealed significantly higher numbers of E. coli in water samples than the
      culture-based assay in each agricultural watershed. The new Q-PCR assay can
      facilitate the quantification of E. coli in a single water sample in < 3 h,
      including melt curve analysis, across a range of agricultural water quality
      conditions.

PMID- 17433481
TI  - The resistance to detachment of dairy strains of Listeria monocytogenes from
      stainless steel by shear stress is related to the fluid dynamic characteristics
      of the location of isolation.
AB  - Strains of Listeria monocytogenes isolated from artisanal Portuguese cheese
      making dairies were divided into two categories on the basis of the locations
      from which they were isolated: strains from dynamic locations were those that
      were habitually exposed to flowing liquids during the process of cheese-making,
      whereas those from static locations were rarely, if ever, exposed to the shear
      stresses generated by liquid flows. The strength of attachment to stainless steel
      discs of all of these strains was obtained using a radial flow chamber. Initial
      attachment strengths to stainless steel (after a 0.5 h contact time) of L.
      monocytogenes strains were greater for the 5 isolates from surfaces exposed to
      flow (dynamic isolates) than for most (3 out of 4) of those that were not (static
      isolates). After a 24 h contact time, attachment strength of all isolates reached
      similar levels. These results suggest that strains having high initial attachment
      strength are more likely to persist on surfaces exposed to flow than strains
      having low initial attachment strength. The numerical values of shear forces
      obtained could prove useful in the rational design of cleaning and
      decontamination procedures in food processing facilities.

PMID- 17433482
TI  - Metabolic engineering of ketocarotenoids biosynthesis in the unicelullar
      microalga Chlamydomonas reinhardtii.
AB  - Most higher plants and microalgae are not able to synthesize ketocarotenoids. In
      this study the unicellular chlorophyte Chlamydomonas reinhardtii has been
      genetically engineered with the beta-carotene ketolase cDNA from Haematococcus
      pluvialis, bkt1 (GeneBank accession no. X86782), involved in the synthesis of
      astaxanthin, to obtain a transgenic microalga able to synthesize ketocarotenoids.
      The expression of bkt1 was driven by the Chlamydomonas constitutive promoter of
      the rubisco small subunit (RbcS2) and the resulting protein was directed to the
      chloroplast by the Chlamydomonas transit peptide sequences of Rubisco small
      subunit (RbcS2) or Ferredoxin (Fd). In all transformants containing the bkt1 gene
      fused to the RbcS2 or the Fd transit peptides a new pigment with the typical
      ketocarotenoid spectrum was detected. Surprisingly this ketocarotenoid was not
      astaxanthin nor canthaxanthin. The ketocarotenoid was identified on the basis of
      its mass spectrum as 3,3'-dihydroxy-beta,epsilon-carotene-4-one (4-keto-lutein)
      or its isomer ketozeaxanthin.

PMID- 17433483
TI  - Construction of thermotolerant yeast expressing thermostable cellulase genes.
AB  - Kluyveromyces marxianus NBRC1777 was identified as a thermotolerant yeast and was
      developed as a host for the expression of thermostable cellulase genes. The
      previously isolated genes for thermostable endo-beta-1,4-glucanase,
      cellobiohydrolase, and beta-glucosidase were introduced into the chromosome of K.
      marxianus and successfully expressed under the control of high-expression
      promoters. The recombinant K. marxianus expressing cellulase genes became able to
      grow in synthetic medium containing cellobiose or carboxymethyl-cellulose as the
      single carbon source. Moreover, the recombinant strain produced 43.4 g/L ethanol
      from 10% cellobiose. These results suggest that K. marxianus may afford a useful
      host system, which may be applicable to the simultaneous saccharification and
      fermentation and the foundation of cellulose consolidated bioprocessing.

PMID- 17433484
TI  - The design, construction and function of a new chimeric anti-CD20 antibody.
AB  - A novel murine IgM-type anti-human CD20 monoclonal antibody (mAb) 1-28 was
      prepared in our Lab, which can induce apoptosis and inhibit proliferation of
      Daudi and Raji cells. However, the efficacy of 1-28mAb in human cancer therapy is
      likely to be limited by human anti-mouse antibody responses. A chimeric antibody,
      C1-28, containing 1-28mAb variable region genes fused to human constant region
      genes (gamma 1, kappa) was constructed. However, C1-28 lost the antigen-binding
      activity. Here, using sequence similarity and known 3D structure of antibody
      variable regions as template, the spatial conformations of 1-28 variable regions
      (i.e. V(H) and V(L)) were analyzed with computer-guided homology modeling
      methods. According to the surface electrostatic distribution and interaction free
      energy analysis, the relationship between structure and stability of 1-28
      variable regions was studied theoretically and a new chimeric anti-CD20 antibody
      scFv-Ig named 5S was designed. Expression level of 5S in the culture supernatant
      was determined to be around 50mug/mL using sandwich ELISA method with chimeric
      antibody Rituxan as reference. 5S retained its murine counterpart's binding
      activity by fluorescence-activated cell-sorting analysis. Furthermore, it could
      kill CD20 positive Daudi and Raji cells by complement-dependent cytotoxicity. For
      binding affinity often decreased even lost when IgM antibody was constructed into
      chimeric IgG1 form, our success give a hint about how to construct a IgG1-type
      chimeric antibody from IgM-type murine antibody to preserve its binding activity.

PMID- 17433485
TI  - A novel cyclic isomaltooligosaccharide (cycloisomaltodecaose, CI-10) produced by
      Bacillus circulans T-3040 displays remarkable inclusion ability compared with
      cyclodextrins.
AB  - Cyclodextrans (CIs) are cyclic isomaltooligosaccharides and only CI-7, CI-8, and
      CI-9 were known. CI-7, CI-8, and CI-9, consisting of seven, eight, and nine
      glucoses, respectively, bound by alpha-(1-->6) linkages, are known to be produced
      by T-3040 strain of Bacillus circulans. However, we have found, using 13C NMR and
      mass spectrometry, that this strain also produces CI-10, CI-11 and CI-12. These
      large CIs are very soluble in water and inhibit the glucan synthesis of
      glucansucrases to the same degree as do the smaller CIs. The CIs were thought to
      be poor at forming inclusion complexes with chemical compounds, due to their
      flexible alpha-(1-->6)-glucosidic structure. Among these six CIs, CI-10 was much
      better at forming an inclusion complex, and it ability to do so was as good as
      cyclodextrins, as determined by its ability to stabilize the color of Victoria
      blue B. Therefore, CI-10 may be the most commercially useful CI.

PMID- 17433486
TI  - Sequence analysis of Jembrana disease virus strains reveals a genetically stable
      lentivirus.
AB  - Jembrana disease virus (JDV) is a lentivirus associated with an acute disease
      syndrome with a 20% case fatality rate in Bos javanicus (Bali cattle) in
      Indonesia, occurring after a short incubation period and with no recurrence of
      the disease after recovery. Partial regions of gag and pol and the entire env
      were examined for sequence variation in DNA samples from cases of Jembrana
      disease obtained from Bali, Sumatra and South Kalimantan in Indonesian Borneo. A
      high level of nucleotide conservation (97-100%) was observed in gag sequences
      from samples taken in Bali and Sumatra, indicating that the source of JDV in
      Sumatra was most likely to have originated from Bali. The pol sequences and,
      unexpectedly, the env sequences from Bali samples were also well conserved with
      low nucleotide (96-99%) and amino acid substitutions (95-99%). However, the
      sample from South Kalimantan (JDV(KAL/01)) contained more divergent sequences,
      particularly in env (88% identity). Phylogenetic analysis revealed that the
      JDV(KAL/01)env sequences clustered with the sequence from the Pulukan sample
      (Bali) from 2001. JDV appears to be remarkably stable genetically and has
      undergone minor genetic changes over a period of nearly 20 years in Bali despite
      becoming endemic in the cattle population of the island.

PMID- 17433487
TI  - The additional prognostic power of diabetes mellitus on coronary flow reserve in
      patients with suspected coronary artery disease.
AB  - AIMS: The aim of the present study was to assess the relative prognostic value of
      coronary flow reserve (CFR) and diabetes mellitus (DM) in patients with suspected
      coronary artery disease (CAD). METHODS: We prospectively studied 347 inhospital
      patients with chest pain. Coronary angiography was performed in 281 patients
      (81%). All patients underwent a transthoracic echocardiographic study to evaluate
      left ventricular function and a stress vasodilator transoesophageal
      echocardiographic study to evaluate simultaneously CFR and the degree of aortic
      atherosclerosis (AA). The primary outcome of the study was cardiovascular
      mortality. RESULTS: During a mean follow-up of 41+/-12 months, 22 patients
      suffered cardiovascular death. Diabetic patients had a significantly higher AA
      grade and tended to have a lower CFR and more often significant CAD. Patients
      with normal CFR had less often significant CAD and tended to have less often DM.
      Significant univariable predictors of cardiovascular survival were DM, LV end
      diastolic diameter, CFR and AA grade. Multivariable regression analysis showed
      that only CFR (hazard ratio (HR) 2.9, P=0.01) and diabetes (HR 3.1, P=0.01) were
      independent predictors of cardiovascular survival. CONCLUSIONS: CFR and DM
      evaluations offer complementary information during vasodilator stress TEE
      testing. Patients with reduced CFR (impaired microcirculatory function) and DM
      have the worst prognosis.

PMID- 17433488
TI  - Quercetin protects human hepatocytes from ethanol-derived oxidative stress by
      inducing heme oxygenase-1 via the MAPK/Nrf2 pathways.
AB  - BACKGROUND/AIMS: Flavonoids, including quercetin, have been reported to have
      potent hepatoprotective effects, which may be associated with HO-1 induction.
      However, since the effect and signaling pathway of quercetin involved in HO-1
      induction against alcoholic liver damage are still not fully understood, this is
      the target of the present study. METHODS: Human hepatocytes were incubated with
      ethanol (100 mM) and quercetin (10-200 microM), and cellular damage and HO-1
      activity were measured. Nrf2 expression in cytosolic and nuclear fractions was
      studied following the incubation with MAPK inhibitor(s). RESULTS: Ethanol
      exposure resulted in a sustained glutathione depletion, malondialdehyde
      elevation, and evident release of cellular LDH and AST. Quercetin exerted a dose
      dependent protective effect against alcoholic oxidative stress, and increased the
      EC50 of ethanol by approx. 40%, which is parallel to HO-1 induction with
      quercetin. Zinc protoporphyrin-9 abrogated the protective effect and dramatically
      enhanced ethanol cytotoxicity. SB203580 (p38 inhibitor) and especially PD98059
      (ERK inhibitor) blocked quercetin-derived HO-1 induction and Nrf2 translocation,
      and subsequently inhibited the quercetin-related protection. CONCLUSIONS: HO-1 up
      regulation by quercetin protected human hepatocytes from ethanol-induced
      oxidative stress. Among MAPK signaling pathways, p38 and ERK mediated quercetin
      derived Nrf2 translocation into nuclei and subsequent induction of HO-1 activity,
      and the latter showed a stronger mediating effect.

PMID- 17433489
TI  - Institutional ethics policies on medical end-of-life decisions: a literature
      review.
AB  - OBJECTIVES: The responsibility of healthcare administrators for handling
      ethically sensitive medical practices, such as medical end-of-life decisions
      (MELDs), within an institutional setting has been receiving more attention. The
      overall aim of this paper is to thoroughly examine the prevalence, content,
      communication, and implementation of written institutional ethics policies on
      MELDs by means of a literature review. METHODS: Major databases (Pubmed, Cinahl,
      PsycINFO, Cochrane Library, FRANCIS, and Philosopher's Index) and reference lists
      were systematically searched for all relevant papers. Inclusion criteria for
      relevance were that the study was empirically based and that it focused on the
      prevalence, content, communication, or implementation of written institutional
      ethics policies concerning MELDs. RESULTS: Our search yielded 19 studies of
      American, Canadian, Dutch and Belgian origin. The majority of studies dealt with
      do-not-resuscitate (DNR) policies (prevalence: 10-89%). Only Dutch and Belgian
      studies dealt with policies on pain and symptom control (prevalence: 15-19%) and
      policies on euthanasia (prevalence: 30-79%). Procedural and technical aspects
      were a prime focus, while the defining of the specific roles of involved parties
      was unclear. Little attention was given to exploring ethical principles that
      question the ethical function of policies. In ethics policies on euthanasia,
      significant consideration was given to procedures that dealt with conscientious
      objections of physicians and nurses. Empirical studies about the implementation
      of ethics policies are scarce. CONCLUSIONS: With regard to providing support for
      physicians and nurses, DNR and euthanasia policies expressed support by primarily
      providing technical and procedural guidelines. Further research is needed whether
      and in which way written institutional ethics policies on MELDs could contribute
      to better end-of-life care.

PMID- 17433490
TI  - Heart disease in psoriasis.
AB  - Psoriasis has been traditionally viewed as an inflammatory skin disorder of
      unknown origin. Recent advances in the immunopathogenesis and genetics of
      psoriasis have broadened our understanding of psoriasis. Psoriasis is now
      considered a systemic inflammatory condition analogous to other inflammatory
      immune disorders. Patients with other immune disorders, such as systemic lupus
      erythematosus or rheumatoid arthritis, are known to be at increased risk of heart
      disease. Similarly, patients with psoriasis may carry an excess risk of heart
      disease, which would represent an important previously unrecognized cause of
      morbidity and mortality. This review summarizes the current evidence for an
      increased cardiovascular risk in patients with psoriasis and outlines deficits in
      our knowledge in this area.

PMID- 17433491
TI  - Measuring handwashing performance in health service audits and research studies.
AB  - Handwashing is regarded as the most effective way of controlling healthcare
      associated infection. A search of the literature identified 42 intervention
      studies seeking to increase compliance in which the data were collected by
      directly observing practice. The methods used to undertake observation were so
      poorly described in most studies that it is difficult to accept the findings as
      reliable or as valid indicators of health worker behaviour. Most studies were
      limited in scope, assessing the frequency of handwashing in critical care units.
      The ethical implications of watching health workers during close patient contact
      were not considered, especially when observation was covert or health workers
      were misinformed about the purpose of the study. Future studies should take place
      in a range of clinical settings to increase the generalizability of findings.
      Observation should be timed to capture a complete picture of 24h activity and
      should include all health workers in contact with patients because all have the
      potential to contribute to cross-infection. Reported details of observation
      should include: vantage of data collectors; inter-rater reliability when more
      than one individual is involved; and attempts to overcome the impact of
      observation on usual health worker behaviour. Ideally an additional data
      collection method should be used to corroborate or refute the findings of
      observation, but no well-validated method is presently available.

PMID- 17433492
TI  - Costs of an outbreak of meticillin-resistant Staphylococcus aureus.
AB  - An outbreak of meticillin-resistant Staphylococcus aureus (MRSA) occurred in
      surgical and internal medicine units of a 1752-bed Finnish tertiary care hospital
      during 2003-2004. In order to analyse the costs of this 14-month outbreak,
      patients were categorized as follows: patients with MRSA infections; patients
      with MRSA colonization; patients exposed to MRSA but whose MRSA status remained
      inconclusive; and exposed patients who were negative for MRSA. We reviewed a
      sample of patients' charts to determine the types of clinical infections and
      interviewed staff about the practical implementation of control measures. The
      number of patients and patient-days involved in the outbreak were identified from
      the hospital's databases, with the administrative database supplying unit costs
      of work and materials. Loss of income due to closed beds was analysed. A total of
      266 MRSA-positive patients (114 with infections and 152 colonized) and 797
      patients exposed to MRSA were identified (11,744 contact isolation days). There
      were 1240 patients negative after screening (9880 contact isolation days). Total
      additional costs of MRSA were 386,062 euro (70% for screening and 25% for contact
      isolation). Costs due to meticillin resistance in treatment of MRSA infections
      were 16,000 euro. The income loss for this hospital due to closed beds was
      1,183,808 euro. The high cost of MRSA screening underlines the importance of
      appropriate screening methods. Our model of analysing costs might be useful for
      other hospitals after adapting variables such as local control measures.

PMID- 17433493
TI  - Nosocomial bacterial meningitis in adults: a prospective series of 50 cases.
AB  - In order to evaluate characteristics of nosocomial meningitis in adults, we
      performed a prospective cohort study of 50 episodes of nosocomial bacterial
      meningitis. These cases were confirmed by culture of cerebrospinal fluid (CSF) in
      patients aged >16 years. Classic symptoms of bacterial meningitis (headache, neck
      stiffness and fever) were present in >70% of the episodes, although only a
      minority (41%) presented with impairment of consciousness. Underlying conditions,
      such as a history of neurosurgery, recent head injury, CSF leakage or a distant
      focus of infection, were present in 94% of the episodes. Staphylococcus aureus
      was the most common pathogen in patients with a history of neurosurgery, causing
      10 of 32 episodes (31%). Patients with a distant focus of infection, such as
      otitis, sinusitis or pneumonia were more likely to have meningitis due to
      Streptococcus pneumoniae than patients without [six of nine episodes (67%) vs
      seven of 41 (17%); P=0.01]. Complications occurred in 50% of the episodes and 16%
      of the patients died. Our study confirms that adults with nosocomial meningitis
      are a distinct patient group with specific bacterial pathogens, as compared to
      those with community-acquired bacterial meningitis. Underlying conditions,
      especially a history of neurosurgery or a distant focus of infection, were
      present in the large majority of patients, and mortality and morbidity rates were
      high.

PMID- 17433494
TI  - Infection control practices in public dental care services: findings from one
      South African Province.
AB  - Infection control practices which increase the risk of blood-borne virus
      transmission with associated dental practice in one South African province were
      studied. All 24 state dental clinics were observed for adequate provision to
      carry out good infection prevention and control (IPC) practice, 75 staff
      including dentists, nurses and dental assistants were interviewed to assess IPC
      knowledge and 23 dental procedures were observed. Significant findings were the
      difference between knowledge and practice, despite adequate provisions for safe
      infection control practice. The lack of protective eye wear during a dental
      procedure, not washing hands between patients, not disassembling an item prior to
      disinfection or sterilization, and not using a sterile drill for each patient
      were identified. A rapid method for detection of occult blood was used as a
      marker for inadequate IPC practice. Contaminated dental items of equipment just
      prior to patient use in 25% of equipment tested and 37% of surfaces and
      surrounding areas in the dental clinics and units were recorded. This study
      concludes that, despite provision for safe dental practice available in state
      dental clinics, there was a lack of knowledge application in clinical practice.
      The risk of blood-borne virus transmission in a population with high human
      immunodeficiency virus (HIV) prevalence cannot be ignored.

PMID- 17433495
TI  - Electro-elution, a novel method to remove transmissible spongiform encephalopathy
      associated PrPSc from stainless steel surgical instruments.
AB  - Iatrogenic transmission of transmissible spongiform encephalopathies (TSEs) has
      been demonstrated via surgical instruments and there is concern over the efficacy
      of conventional decontamination techniques used to reprocess reusable
      instruments. This paper describes the development of a novel cleaning method,
      'electro-elution', to remove TSE disease-specific abnormal protein PrP(Sc) from
      the surface of stainless steel surgical instruments. The electro-elution process
      subjects the stainless steel instrument to an electrical current in the presence
      of an electrolytic buffer to remove protein deposits. Stainless steel discs were
      contaminated with infectious brain homogenate and subjected to a range of
      conditions to determine the ability of electro-elution to remove the deposits. To
      determine whether there was any residual PrP(Sc) remaining on the disc after
      electro-elution, a novel detection method, 'direct blotting', was also developed.
      Direct blotting utilizes a process of passive transfer of proteins directly from
      the surface of the instrument to a proteophilic membrane for detection. Our study
      shows that electro-elution has the ability to effectively remove, and possibly
      degrade, disease-associated PrP(Sc) from the surface of stainless steel surgical
      instruments.

PMID- 17433496
TI  - Medication errors among acutely ill and injured children treated in rural
      emergency departments.
AB  - STUDY OBJECTIVE: We identify the incidence, nature, and consequences of
      medication errors among acutely ill and injured children receiving care in a
      sample of rural emergency departments (EDs). METHODS: Two pediatric pharmacists
      applied a medication error data collection instrument to the medical records of
      all critically ill children (highest triage category) treated in 4 northern
      California rural EDs between January 2000 and June 2003. Physician-related
      medication errors were defined as those involving wrong dose, wrong or
      inappropriate medication for condition, wrong route, or wrong dosage form. Wrong
      dose was determined by preset criteria, with doses above or below 10% to 25% of
      correct dose considered errors, depending on class of medication. Medication
      errors were classified into categories A through I under 3 broader categories,
      including errors having the potential to cause harm (A), errors that cause no
      harm (B to D), and errors that cause harm to the patient (E to I). RESULTS:
      Complete data were available from 177 (97.3%) of the 182 patients identified as
      having been triaged in the highest category during the study period. A total of
      84 medication errors were identified among 69 patients, resulting in a medication
      error incidence of 39.0%. Twenty-four physician-related medication errors were
      identified among 21 patients, resulting in a physician-related medication error
      incidence of 11.9%. Among the 69 patients with medication errors, 11 had errors
      categorized as having the potential to cause harm (15.9%), and 58 had errors
      categorized as causing no harm (85.5%). CONCLUSION: We found a high incidence of
      medication errors and physician-related medication errors among the acutely ill
      and injured children presenting to rural EDs in northern California. None of the
      medication errors identified caused harm to the patients included in this study.

PMID- 17433497
TI  - Humming is as effective as Valsalva's maneuver and Trendelenburg's position for
      ultrasonographic visualization of the jugular venous system and common femoral
      veins.
AB  - STUDY OBJECTIVE: The purpose of this study is to compare ultrasonographic
      visualization of the jugular and common femoral veins by using a novel technique
      (humming) and 2 conventional techniques (Valsalva's maneuver and Trendelenburg's
      position). The Valsalva's maneuver and Trendelenburg's position are common
      methods for producing venous distention, aiding ultrasonographically guided
      identification and cannulation of the jugular and common femoral veins. We
      hypothesize that humming is as effective as either Valsalva's maneuver or
      Trendelenburg's position for distention and ultrasonographic visualization of
      these procedurally important blood vessels. Herein, we investigate a new method
      of venous distension that may aid in the placement of central venous catheters by
      ultrasonographic guidance. METHODS: Healthy, normal volunteers aged 28 to 67
      years were enrolled. Each subject's internal jugular, external jugular, and
      common femoral veins were measured in cross-section by ultrasonograph during rest
      (baseline), humming, Valsalva's maneuver, and Trendelenburg's position. Three
      measurements were recorded per observation in each position. Subjects were used
      as their own controls, and measurements were normalized to percentage increase in
      diameter during each maneuver or position for later comparison. RESULTS: The
      study population consisted of 7 subjects, with a mean age of 47 years. Cross
      sectional area was calculated for each vessel in 3 groups: baseline/control,
      Valsalva, Trendelenburg, and humming. The mean percentage change (+/-SD) relative
      to baseline cross-sectional area of the jugular vessels for each subject were
      external jugular vein: humming 134%+/-25% (95% confidence interval [CI] 124.9% to
      146.9%), Valsalva 136%+/-23% (95% CI 121.3% to 147.5%), Trendelenburg 137%+/-32%
      (95% CI 120.7% to 156.9%); internal jugular vein: humming 137%+/-27% (95% CI
      119.4% to 148.2%), Valsalva 139%+/-24% (95% CI 122.4% to 148.7%), Trendelenburg
      141%+/-35% (95% CI 116.5% to 156.5%); common femoral vein: humming 131%+/-15%
      (95% CI 120.4% to 139.1%), Valsalva 139%+/-18% (95% CI 127.9% to 150.4%),
      Trendelenburg 132%+/-24% (95% CI 113.3% to 142.9%). CONCLUSION: All 3 maneuvers
      distended the external jugular, internal jugular, and common femoral veins
      compared to baseline. There was no important difference in magnitude of cross
      sectional area between any of the 3 maneuvers when compared with one another.
      Humming shares many physiologic similarities to Valsalva's maneuver and may be
      more familiar and easier to perform during procedures such as
      ultrasonographically guided central venous catheter placement and insertion of
      external jugular intravenous catheters.

PMID- 17433498
TI  - Ultrasonographically guided insertion of a 15-cm catheter into the deep brachial
      or basilic vein in patients with difficult intravenous access.
AB  - STUDY OBJECTIVE: Standard length (3 to 5 cm) intravenous catheters in the deep
      brachial or basilic vein tend to dislodge prematurely. We assess the safety and
      longevity of a 15-cm catheter inserted in these veins by a novel
      ultrasonographically guided technique. METHODS: This is a prospective cohort
      study conducted in an urban teaching emergency department (ED). Adult subjects
      were enrolled if 2 peripheral intravenous insertion attempts had failed. A 3.2
      cm, 18-gauge catheter was first inserted into the deep brachial or basilic vein
      under ultrasonographic guidance. In a separate step, a wire was inserted through
      this catheter, and a 15-cm, 16-gauge catheter was placed over the wire and left
      in place for up to 3 days. Primary outcomes were time to securing access and rate
      of loss of access. Secondary outcomes included complication rates and subject
      satisfaction. RESULTS: Twenty-five subjects were enrolled; 23 catheters were
      successfully placed. Median time required for initial vein cannulation was 3
      minutes (interquartile range [IQR] 2 to 7 minutes) and for securing the 15-cm
      catheter was an additional 4 minutes (IQR 3 to 5 minutes). Median duration of
      access was 26 hours (IQR 10 to 47 hours). The only complication was early
      infiltration in 1 subject. All subjects rated satisfaction as 4 or 5 on a 5-point
      Likert scale. CONCLUSION: We present a promising alternative to central venous
      catheterization in patients with difficult intravenous access. This technique
      appears to be fast, safe, and well tolerated by adult patients.

PMID- 17433499
TI  - Adrenomedullin is a novel adipokine: adrenomedullin in adipocytes and adipose
      tissues.
AB  - Adrenomedullin (AM) is a multifunctional regulatory peptide that is produced and
      secreted by various types of cells. The production and the secretion of AM have
      been demonstrated in cultured adipocytes and adipose tissues. Inflammatory
      cytokines such as tumor necrosis factor-alpha (TNF-alpha) and lipopolysaccharide
      are strong stimulators for AM expression in adipocytes. Furthermore, AM
      expression in the adipose tissue is increased in obesity, and plasma
      concentrations of AM are increased in obese subjects. One possible
      (patho)physiological role of AM secreted by adipose tissue may be actions against
      complications of the metabolic syndrome characterized by obesity, type 2 diabetic
      mellitus and hypertension, via its antioxidant and potent vasodilator effects.
      These findings indicate that AM is a new member of the adipokine family.

PMID- 17433500
TI  - Increased oxidative stress during hyperglycemic cerebral ischemia.
AB  - In this review, we summarize the role of hyperglycemia during cerebral ischemia.
      Hyperglycemia occurring during experimental and clinical stroke has been
      associated with increased cerebral damage. Increased oxidative stress resulting
      from hyperglycemia is believed to contribute to the exacerbated damage. More
      specifically, superoxide, nitric oxide and peroxynitrite are believed to play an
      important role in cerebral damage. This also involves increased recruitment of
      various blood cells to the ischemic zone that contribute to inflammation. We
      present data from our group and others that demonstrate that free radical
      production is increased during hyperglycemic stroke in rodents. Recent data
      suggest that inflammation is an important component of ischemic damage under both
      normo- and hyperglycemic conditions. We summarize numerous studies that indicate
      that a variety of antioxidant (inhibition of free radical production, scavenging
      of free radicals and increasing free radical degradation) and anti-inflammatory
      strategies decrease cerebral infarction. Finally, we compare the success of some
      of these strategies in clinical trials compared to the animal models.

PMID- 17433501
TI  - Plasma carotenoids and tocopherols and cognitive function: a prospective study.
AB  - As a site of high metabolic activity, the brain is particularly susceptible to
      oxidative damage. We explored the association between plasma antioxidants and
      cognition. In 858 female participants of the Nurses' Health Study, aged 70+
      years, we measured plasma carotenoids and tocopherols in 1989-1990, and assessed
      cognitive function by telephone beginning in 1995-2001; assessments were repeated
      twice at 2-year intervals. We used linear regression to estimate multivariable
      adjusted mean cognitive performance at the initial assessment by quartile of
      antioxidants, and longitudinal models for analyzing cognitive decline over 4
      years. Higher antioxidant levels were not associated with initial performance or
      decline. Mean difference in initial global composite score (averaging all six
      cognitive tests) for the top versus bottom quartile of total carotenoids was 
      0.05 standard units (95% confidence interval [CI] -0.19, 0.09), and 0.04 units
      for total tocopherols (95% CI -0.10, 0.18). Individual antioxidants were not
      associated with cognition. Overall, total plasma carotenoids or tocopherols were
      not related to cognition in women.

PMID- 17433504
TI  - Activation of glycogen synthase kinase-3 inhibits protein phosphatase-2A and the
      underlying mechanisms.
AB  - The activity of protein phosphatase-2A (PP-2A) is significantly suppressed in the
      brain of Alzheimer's disease (AD) patients, but the mechanism is not understood.
      Here, we found an in vivo association of glycogen synthase kinase 3beta (GSK
      3beta) with inhibitor-2 of PP-2A (I(2)(PP-2A)). The activation of GSK-3 resulted
      in accumulation of I(2)(PP-2A) with concomitant suppression of PP-2A activity and
      increases of tau phosphorylation in HEK293, N2a and PC12 cells, while inhibition
      of GSK-3 caused decreases of I(2)(PP-2A) with increased PP-2A activity and
      decreased tau phosphorylation. A positive correlation between GSK-3beta and
      I(2)(PP-2A) (R=0.9158) and a negative correlation between GSK-3beta and PP-2A (R=
      0.9166) were detected. GSK-3 activation did not affect I(2)(PP-2A) mRNA level,
      while it increased the mRNA level of a heterogeneous ribonucleoprotein A18 (hnRNP
      A18). The activation of GSK-3 increased the expression and the activity of
      proteasome system. It suggests that activation of GSK-3 inhibits PP-2A through up
      regulation of I(2)(PP-2A) with hnRNP A18-involved mechanism.

PMID- 17433502
TI  - Effects of aging and caloric restriction on dentate gyrus synapses and glutamate
      receptor subunits.
AB  - Caloric restriction (CR) attenuates aging-related degenerative processes
      throughout the body. It is less clear, however, whether CR has a similar effect
      in the brain, particularly in the hippocampus, an area important for learning and
      memory processes that often are compromised in aging. In order to evaluate the
      effect of CR on synapses across lifespan, we quantified synapses stereologically
      in the middle molecular layer of the dentate gyrus (DG) of young, middle aged and
      old Fischer 344 x Brown Norway rats fed ad libitum (AL) or a CR diet from 4
      months of age. The results indicate that synapses are maintained across lifespan
      in both AL and CR rats. In light of this stability, we addressed whether aging
      and CR influence neurotransmitter receptor levels by measuring subunits of NMDA
      (NR1, NR2A and NR2B) and AMPA (GluR1, GluR2) receptors in the DG of a second
      cohort of AL and CR rats across lifespan. The results reveal that the NR1 and
      GluR1 subunits decline with age in AL, but not CR rats. The absence of an aging
      related decline in these subunits in CR rats, however, does not arise from
      increased levels in old CR rats. Instead, it is due to subunit decreases in young
      CR rats to levels that are sustained in CR rats throughout lifespan, but that are
      reached in AL rats only in old age.

PMID- 17433503
TI  - Alterations in NMDA receptor subunit densities and ligand binding to glycine
      recognition sites are associated with chronic anxiety in Alzheimer's disease.
AB  - Glutamatergic deficits are established neuropathological features of Alzheimer's
      disease (AD) and are known to correlate with cognitive impairments. In contrast,
      the role of glutamatergic alterations in behavioral and psychological symptoms of
      dementia (BPSD) is unclear. There is considerable preclinical evidence for the
      importance of glycine recognition sites (GlyRS) of N-methyl-D-aspartate (NMDA)
      receptors in the regulation of anxiety behaviors. This study aimed to correlate
      several glutamatergic measures with chronic anxiety in AD. Twenty-one AD patients
      assessed by the Neuropsychiatric Inventory (NPI) were divided into low anxiety
      (LA) and high anxiety (HA) subgroups. GlyRS and NMDA channel were measured by
      brain homogenate binding with [(3)H]MDL105,519 and [(3)H]MK-801, respectively.
      Densities of NMDA receptor NR2A, NR2B and alternate spliced NR1 subunits were
      quantified by immunoblotting. We found that the binding affinity to GlyRS was
      significantly higher in HA compared to LA, and this higher GlyRS affinity
      correlated with selective reduction of NR2A density as well as with elevated
      anxiety scores. Our observations suggest a novel mechanism whereby subunit
      specific changes in the NMDA receptor complex may be linked to chronic anxiety in
      AD via effects on GlyRS function. We propose that NR2A and GlyRS should be
      further assessed as novel targets of behavioral pharmacotherapy in AD.

PMID- 17433505
TI  - Synthesis and biological activity of imidazopyridine anticoccidial agents: part
      I.
AB  - Coccidiosis is the major cause of morbidity and mortality in the poultry
      industry. Protozoan parasites of the genus Eimeria invade the intestinal lining
      of the avian host causing tissue pathology, poor weight gain, and in some cases
      mortality. Resistance to current anticoccidials has prompted the search for new
      therapeutic agents with potent in vitro and in vivo activity against Eimeria.
      Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent
      protein kinase (PKG). In this study, we present the synthesis and biological
      activity of imidazo[1,2-a]pyridine anticoccidial agents. From this series,
      several compounds showed subnanomolar in vitro activity and commercial levels of
      in vivo activity. However, the potential genotoxicity of these compounds
      precludes them from further development.

PMID- 17433506
TI  - Diminished intestinal colonization by Clostridium difficile and immune response
      in mice after mucosal immunization with surface proteins of Clostridium
      difficile.
AB  - Clostridium difficile pathogenesis is mainly due to toxins A and B. However, the
      first step of pathogenesis is the colonization process. We evaluated C. difficile
      surface proteins as vaccine antigens to diminish intestinal colonization in a
      human flora-associated mouse model. First, we used the flagellar cap protein FliD
      of C. difficile, in order to test several immunization routes: intranasal,
      rectal, and intragastric. The rectal route, which is the most efficient, was used
      to vaccine groups of mice with different antigen combinations. After
      immunizations, the mice were challenged with the toxigenic C. difficile and a
      significant statistical difference between the control group and the immunized
      groups was observed in the colonization levels of C. difficile.

PMID- 17433507
TI  - Recombinant murine gammaherpesvirus 68 (MHV-68) as challenge virus to test
      efficacy of vaccination against chronic virus infections in the mouse model.
AB  - Efficient vaccines against AIDS, Hepatitis C and other persistent virus
      infections are urgently needed. Vaccine development has been especially hampered
      by the lack of suitable small animal models to reliably test the protective
      capacity of candidate vaccines against such chronic viral infections. A natural
      mouse pathogen such as MHV-68 that persists lifelong after infection, appears to
      be a particularly promising candidate for a more relevant model system. Here, we
      investigated infections with recombinant MHV-68 as novel mouse challenge model to
      test the efficacy of heterologous vaccines based on recombinant modified vaccinia
      virus Ankara (MVA). To apply ovalbumin (OVA) as a model antigen, we constructed
      the recombinant virus MHV-68-OVA by BAC technology and characterized genetic
      stability and replicative capacity of the virus in vitro and in vivo. We
      demonstrated the ability of MHV-68-OVA to produce ovalbumin upon tissue culture
      infection. Moreover, the use of MHV-68-OVA-infected target cells allowed for
      efficient ex vivo amplification of OVA-specific, MHC class I-restricted CD8 T
      cells derived from MVA-OVA-vaccinated C57BL/6 mice. Finally, we immunized C57BL/6
      mice with MVA-OVA and challenged the animals with MHV-68-OVA testing different
      time points and routes of infection. Vaccinated mice were infected with MHV-68
      OVA but showed reduced viral loads in the acute and latent phase of challenge
      infection. These data strongly suggest the usefulness of the MHV-68 challenge
      model for further evaluation of recombinant vaccines against persisting virus
      infections.

PMID- 17433508
TI  - Dynamics of trace metals in organisms and ecosystems: prediction of metal
      bioconcentration in different organisms and estimation of exposure risks.
AB  - Metal ions interact with biological materials and their decomposition products by
      ligation (coordination complex-formation with certain moieties containing O, N,
      S, etc.). The extent of this interaction depends on the identities of both ligand
      and metal ion and can be described by some equation derived from perturbation
      theory. Uptake of metal ions - including highly toxic ones - from soils is
      controlled by a competition between root exudate components and soil organic
      matter (SOM) for the ions. SOM consists of a variety of potential ligands which
      evolve during humification towards more efficient binding (retention) of metals
      such as Cu, Ni, Cr but also of toxicants like U, Cd. The actual way of
      interaction can be inferred from stoichiometry of the involved compounds and the
      C/N ratio in the soil, providing predictions as to which metals will be most
      efficiently shuttled into green plants or fungi, respectively. The latter,
      selective process is crucial for closing nutrient cycles and sensitively depends
      on C/N ratio and the extent of "forcing" by onfalling leaf or needle litter.
      Therefore, analytical data on the soil can be used to predict possible risks of
      exposition to toxic metals also for human consumption of plant parts.

PMID- 17433509
TI  - How do objective and subjective assessments of neighbourhood influence social and
      physical functioning in older age? Findings from a British survey of ageing.
AB  - The objective was to investigate associations between type of area, individuals'
      perceptions of their neighbourhoods, and indicators of social and physical
      functioning. Social functioning was measured using numbers of social activities
      and frequency of social contacts in the past month. Physical functioning was
      measured with Townsend's Activities of Daily Living scale. The study was a
      British cross-sectional population survey of people aged 65 plus living at home.
      Multilevel analyses indicated that respondents who lived in affluent areas were
      less likely to have low levels of social activity independently of individual
      demographic and socio-economic characteristics. Individuals' perceptions of the
      area as neighbourly and having good facilities were also independently associated
      with lower likelihood of low social activities. Affluence of the area and
      perceived neighbourhood were associated with physical functioning, although these
      associations disappeared once adjustment was made for individuals'
      characteristics. Both objective and more subjective measures of the neighbourhood
      independently contributed to our understanding of the determinants of social and
      physical functioning in older age. The unique value of this paper is its
      inclusion of the influence of perceived neighbourhood on the social and physical
      functioning of an older population, which are key components of active ageing.

PMID- 17433510
TI  - Sociocultural barriers to cervical screening in South Auckland, New Zealand.
AB  - Cervical screening has been subject to intense media scrutiny in New Zealand in
      recent years prompted by a series of health system failings through which a
      number of women developed cervical cancer despite undergoing regular smears. This
      paper considers why underscreening persists in a country where cervical screening
      has a high profile. It explores how the promotion of cervical screening has
      impacted on the decisions of women to undergo a smear test. Ideas of risk and the
      new public health are deployed to develop a context for thinking about screening
      as a form of governing the body. Qualitative interviews with 17 women who were
      overdue for a cervical smear were undertaken in 2001-2002, yielding
      understandings of their knowledge of screening and their reasons for
      postponement. Nine providers of screening services were also interviewed.
      Concurrent with socioeconomic limitations, concerns over exposing one's body
      loomed large in women's reasons for delaying being screened. In particular,
      feelings of shyness and embarrassment were encountered among Maori and Pacific
      women for whom exposing bodies in the process of smear taking compromises
      cultural beliefs about sacredness. We conclude that medicalization of the body
      has, paradoxically, assisted many women in dealing with the intrusion of
      screening. For others, compliance with the exhortations to be screened brings a
      high emotional and cultural cost which should at least be considered in health
      policy debates.

PMID- 17433511
TI  - Correlates of family, school, and peer variables with adolescent substance use in
      Taiwan.
AB  - This study examines adolescent substance use in relation to family, peer and
      school factors in the context of Taiwan. Information on family characteristics,
      satisfaction with performance at school, and peer influence was collected using a
      case-control study in which a two-stage method was applied to ascertain substance
      use. A set of hypotheses on interrelationships of substance use (tobacco,
      alcohol, betel, illicit drugs) and influences were tested with a structural
      equation model. There was a strong negative relation between family factors and
      peer relationships (p=0.005). Family variables played an important role in
      motivation and effort to study (p=0.004). High motivation and effort to study
      (p=0.0012) and good school adjustment (p=0.078) led to higher satisfaction with
      performance at school. A significant positive association between peer
      relationships and deviant peer behaviour was observed (p<0.001). Satisfaction
      with performance at school was negatively related to deviant peer behaviour
      (p=0.052). The direct effect of deviant peer behaviour was marginally
      statistically significant (p=0.011) and an indirect effect of family factors on
      substance use was statistically significant (p=0.041). In conclusion, the study
      found that a strong family-peer relationship and family influence has a
      significant effect on substance use.

PMID- 17433512
TI  - Does "community social capital" contribute to population health?
AB  - Robert Putnam showed that a social capital index, created as a weighted sum of 14
      variables chosen to describe the civic degree of sociability and community
      mindedness, is correlated with many community outcomes, such as education, child
      well-being, crime, and the total mortality rate. Although correlation does not
      establish causation, we can find that in a large number of studies this index, a
      selection of its elements, or similar measures register as significantly
      correlated with health variables, virtually always in a direction consistent with
      the hypothesis that social capital improves health. The potential benefit of this
      relationship is substantial, especially if it proves to be robust to differences
      in time and place, statistical contexts, and ultimately if the relation can be
      supported to be causal. This paper subjects the social capital and health
      hypothesis to an expanded set of rigorous tests, which, by surviving, it becomes
      stronger or, by failing, its weaknesses are better revealed. The paper seeks to
      extend this body of research by a combination of study characteristics that are
      each relatively unusual in social capital and health research. Though causality
      cannot be established by these tests, the work shows that the association of
      social capital with health is quite robust when challenged in the following ways:
      (1) seven different health measures are studied, including five mortality rates;
      (2) the 48 contiguous states are observed at six points in time covering the
      years from 1978 to 1998 over four year intervals, thus forming a panel; (3) the
      multivariate tests feature economic variables from the production of health
      literature; and (4) a statistical method (instrumental variables) is applied to
      account for the possibility that omitted variables are confounding the social
      capital estimates. The results and the discussion find cases for which the social
      capital and health hypothesis performs only weakly, but, on the whole, the
      hypothesis is remarkably robust to these variations.

PMID- 17433513
TI  - Perceived job stress and sleep-related breathing disturbance in Japanese male
      workers.
AB  - To examine the association of job stress with sleep-related breathing disturbance
      (SBD), a cross-sectional sample of 1940 males aged 17-83 (mean 45) years in 292
      small and medium-sized enterprises in Japan were surveyed by means of a self
      administered questionnaire. Perceived job stress was evaluated by the Japanese
      version of the Generic Job Stress Questionnaire developed by the US National
      Institute for Occupational Safety and Health, which included 13 job stress
      variables. Participants were divided into thirds according to their job stress
      scores. SBD was assessed by the question "Have you ever felt difficulty breathing
      during sleep or has anyone in your family told you that you have such
      difficulty?" SBD was defined as presence of symptoms more than once a month. Risk
      of SBD through job stress was estimated using logistic regression with odds
      ratios (ORs) and 95% confidence intervals (CIs) as measures of association.
      Prevalence of study-defined SBD was 6.7%. Participants who perceived the lowest
      level of social support from supervisors, and highest levels of job future
      ambiguity, interpersonal conflict at the workplace, job dissatisfaction, variance
      in workload, and quantitative workload had significantly increased risk of SBD
      after adjusting for potential confounders. High depressive symptoms, as measured
      by Center for Epidemiologic Studies Depression scale scores of 16 or higher, were
      also significantly associated with increased SDB. Although the results should be
      considered preliminary because of the self-reporting and cross-sectional design,
      data suggest that exposure to high job stress could be a possible risk factor for
      developing or aggravating SBD. Results also indicate that job stress should be
      considered when evaluating SBD in occupational and clinical settings.

PMID- 17433514
TI  - Suitable stimuli to obtain (no) gender differences in the speed of cognitive
      processes involved in mental rotation.
AB  - Gender differences in speed of perceptual comparison, of picture-plane mental
      rotation, and in switching costs between trials that do and do not require mental
      rotation, were investigated as a function of stimulus material with a total
      sample size of N=360. Alphanumeric characters, PMA symbols, animal drawings,
      polygons and 3D cube figures were used with an otherwise completely equivalent
      experimental design in which age and speed-based IQ were comparable across male
      and female groups. Small gender-related differences in speed of perceptual
      comparison were found with the magnitude as well as the direction depending upon
      the stimulus material. Polygons were the only material that produced substantial
      and reliable gender differences in mental rotation speed, and additionally
      revealed gender differences in switching costs. Thus, whereas gender differences
      in paper-pencil mental rotation tests constitute an empirical reality, the
      generalization that men outperform women in the speed of mental rotation was not
      supported in the present experiment.

PMID- 17433515
TI  - Corticotropin-releasing factor test in melancholic patients in depressed state
      versus recovery: a comparative study.
AB  - PURPOSE: Basal adrenocorticotropin hormone (ACTH) and cortisol levels and their
      response to corticotropin-releasing factor (CRF) test were studied in melancholic
      depressive patients in depressed state and recovery, and compared with healthy
      controls. METHODS: Fifty-four outpatients diagnosed with unipolar depressive
      disorder with melancholic features according to DSM-IV and 23 healthy controls
      were included in the study. The Structured Clinical Interview for DSM-IV (SCID
      IV) was used for diagnosis. Twenty-nine patients were in recovery, while 25 were
      in depressed state at the moment of the administration of the CRF test. FINDINGS:
      No differences were found between the recovered and depressed groups with respect
      to CRF test. Lower ACTH and higher cortisol levels with significant differences
      were shown in the neuroendocrine variables at 15, 30, and 60 min, and in peak
      response and increase, in the ACTH and cortisol response curves to CRF challenge
      between the groups of melancholic patients, both recovered and depressed,
      compared with the healthy control subjects. Moreover, recovered and depressed
      melancholic patients had a higher whole cortisol area under the curve with
      significant differences than the healthy control subjects. CONCLUSIONS: The
      crossover clinical status at the moment of the CRF test doesn't differentiate
      changes in the HPA axis in melancholic patients, while we did find significant
      differences in the group of healthy controls in comparison with the groups of
      melancholic patients both in depressive state and recovery. This supports the
      hypothesis that hypothalamic pituitary adrenal (HPA) axis shows alterations that
      remain in depressive patients even after recovery.

PMID- 17433516
TI  - Cytokine imbalance in the pathophysiology of major depressive disorder.
AB  - OBJECTIVE: A substantial body of evidence indicates that dysregulation of the
      immune system is associated with Major Depressive Disorder (MDD). Because most
      cytokines have pleiotropic effects, we measured various subsets of cytokines to
      examine the association between immune response and MDD. METHODS: Forty-eight
      hospitalized MDD patients and 63 normal controls were recruited. We measured in
      vitro monocytic (IL-6 and tumor necrosis factor (TNF)-alpha), Th1 (interferon
      (IFN)-gamma and interleukin (IL)-2), Th2 (IL-4), and Treg (transforming growth
      factor (TGF)-beta1) cytokine production as well as IL-2/IL-4 and IFN-gamma/IL-4
      ratios for both groups. Depressive symptoms were assessed by Hamilton Depression
      Rating Scale. Patients were evaluated before and after 6 weeks of antidepressant
      treatment. RESULTS: At admission, IL-6, TNF-alpha, TGF-beta1 production, and IFN
      gamma/IL-4 ratio were significantly higher, whereas IFN-gamma, IL-2, and IL-4
      were significantly lower in MDD patients. After treatment, IL-6 and TGF-beta1
      production were significantly lower than before treatment. CONCLUSION: We suggest
      that activation of monocytic proinflammatory cytokines, and inhibition of both
      Th1 and Th2 cytokines may be associated with immunological dysregulation in MDD.
      TGF-beta1 may be associated with the regulation of monocytic cytokines as well as
      Th1 and Th2 cytokines in MDD.

PMID- 17433517
TI  - Serum brain-derived neurotrophic factor level in dysthymia: a comparative study
      with major depressive disorder.
AB  - In this present work, it is aimed to demonstrate BDNF serum concentrations in
      patients with dysthymia and to compare them with BDNF serum concentrations in
      patients with major depressive disorder and healthy subjects. The study was
      carried out in Celal Bayar University Hospital, Manisa, Turkey. Seventeen
      patients with dysthymia, 24 patients with major depressive disorder and 26
      subjects without any psychiatric diagnosis and any psychiatric treatment were
      included in the study. The severity of depression was assessed with 17-item HAM
      D. All subjects were asked to give their written consent. Blood samples were
      collected at baseline. Serum BDNF was kept at -70 degrees C before testing, and
      assayed with an ELISA Kit (Promega; Madison, WI, USA), after dilution with the
      Block and Sample solution provided with the kit. The data were subjected to the
      analysis of variance. The BDNF serum concentrations of the dysthymia group
      (mean=28.9+/-9.2 ng/ml) were significantly higher than that of the major
      depressive disorder group (21.2+/-11.3 ng/ml) (p=0.002), and it was not different
      from the level of the control group (31.4+/-8.8 ng/ml). BDNF serum concentrations
      and HAM-D score did not have any significant correlation in the dysthymia and
      major depression groups (r=-0.276, p=0.086). The low level of BDNF in patients
      with dysthymic disorder seems to point out that BDNF changes in mood disorders
      are state-dependent and vary according to the severity of depressive episodes.

PMID- 17433518
TI  - Inhibition by dietary hydroquinone of acetylaminofluorene induction of initiation
      of rat liver carcinogenesis.
AB  - Monocyclic phenolics (MPs) occur widely in foods, both naturally and as synthetic
      antioxidant additives. Several have been shown to inhibit the carcinogenicity of
      a variety of genotoxic carcinogens in various tissues. Hydroquinone (HQ), one of
      the simplest of the MPs, which occurs naturally as the glucose conjugate arbutin,
      was studied for its ability, at low dietary levels, to inhibit the initiating
      effects in the rat liver of the DNA-reactive carcinogen 2-acetylaminofluorene
      (AAF). Male Fischer 344 rats (F344), 8 weeks old at the start of the study, were
      allocated to six groups. HQ was fed daily ad libitum in PMI certified diet at
      either 0.05% (approximately 25 mg/kg bw/d) or 0.2% (approximately 100 mg/kg bw/d)
      for 13 weeks, starting one week before AAF administration was initiated, and at
      the same doses to two groups not receiving AAF. AAF was given intragastrically
      three times a week for 12 weeks at doses of 3mg/kg bw in 0.5% carboxymethyl
      cellulose (CMC) to a basal diet group and two of the groups receiving HQ in the
      diet. Vehicle controls were fed basal diet and administered 0.5% CMC
      intragastrically three times a week. The rats were observed daily and body
      weights were taken before initial dosing and at weekly intervals thereafter. Body
      weight gain over time, terminal body weights and absolute (mg) and relative liver
      weights (relative to body weight) were measured. At the end of the study (13
      weeks), DNA adducts ((32)P-postlabeling), cell proliferation (PCNA
      immunohistochemistry) and preneoplastic hepatocellular altered foci (HAF)
      (glutathione S-transferase-placental type immuno-histochemistry) were measured.
      No significant differences were observed in body weight gains or liver weights.
      AAF produced liver DNA adducts and at the low dose of HQ adduct levels were 90%
      of that for AAF alone, whereas at the high dose adducts were reduced by 33%
      (p<0.05). AAF exposure yielded about a 50% increase in hepatocellular
      proliferation and both HQ doses reduced the AAF-induced increases in
      proliferation by about 25%. Likewise, the AAF-induced GST-P-positive HAF per
      cm(2) of liver tissue were decreased by both doses of HQ by about 50%. Thus,
      under the conditions of this experiment, HQ at both 0.05% and 0.2% in the diet
      diminished AAF-induced cancer initiating effects in rat liver.

PMID- 17433519
TI  - Reproductive safety studies with genistein in rats.
AB  - Genistein is a phytoestrogen that occurs naturally in the diet and is found in a
      wide variety of plant-derived foods especially in soybeans and soy-based foods.
      There is wide spread interest in genistein and related phytoestrogens as
      chemopreventive agents for a variety of human diseases and cancers based on
      epidemiologic evidence of reduced cancer rates in populations with a high intake
      of soy. Soy, and hence its constituents, such as genistein, have been consumed at
      high levels in several Asian populations for many centuries without any apparent
      adverse effects and to the contrary, many health benefits have been associated
      with the ingestion of soy based foods. Concern has been raised, however, of
      potential adverse effects due to the estrogenic and other activities of the
      isoflavones and thus a comprehensive series of safety studies was performed with
      genistein. To assess the teratogenic and fetal toxic potential of genistein,
      several studies were conducted. Genistein was tested in an in vitro rat whole
      embryo culture assay (WEC), which is a preliminary screen, for fetotoxic and
      teratogenic potential, over a concentration range of from 1 to 100 microg/mL.
      Treatment related anomalies were observed at concentrations of >or= 10 microg and
      at 100 microg/mL, all embryos were malformed. Two in vivo embryo fetal
      developmental safety studies were conducted with genistein by oral administration
      (gavage and dietary admix) in which there was no evidence for a teratogenic
      effect. In an oral (gavage) embryonic and fetal development pilot study,
      genistein was administered to rats at dose levels of 0, 20, 150 and 1000
      mg/kg/day from days 6-20 of gestation to females that were allowed to litter and
      rear their offspring up to day 7 of lactation. A slight maternal toxicity at 1000
      mg/kg/day was observed as indicated by decreased body weight and food consumption
      and at this dose, adverse effects in the pups were observed including increased
      pup mortality, poor general condition, reduced pup body weights, and reduced pup
      milk uptake. At the high dose of 1000 mg/kg, no external malformations were
      noted, however some minor visceral and skeletal variations were observed. At the
      low dose of 20 mg/kg/day, an increased mortality, reduced milk uptake, a
      decreased % male sex ratio, and decreased body weights during lactation were
      observed. Due to lack of effects at the mid dose and the small number of animals,
      a relationship to treatment was considered unlikely. In an oral (dietary admix)
      Prenatal developmental safety study, genistein was administered to rats at dose
      levels of 0, 5, 50, 100 and 500 mg/kg/day from day 5-21 of gestation. At 500
      mg/kg, maternal body weight and food consumption were markedly reduced. The
      incidence of resorptions was markedly increased with a corresponding decrease in
      the number of live fetuses per dam. Fetal body weights were also reduced. No
      treatment-related teratogenic effects were noted during external, visceral and
      skeletal examination of fetuses or in body weight normalized anogenital distance.
      On the basis of these studies, it is concluded that genistein has no teratogenic
      potential in vivo at very high doses of up to 1000 mg/kg/day by oral gavage in
      the embryo-fetal toxicity pilot study or up to 500 mg/kg/day by dietary admix in
      the Prenatal developmental study even though these doses were maternally toxic
      and fetal-toxic. In vitro, genistein had teratogenic potential at high
      concentrations in the WEC screening assay, however this was not predictive of the
      in vivo findings. On the basis of the definitive Prenatal development study, the
      NOAEL for maternal toxicity and adverse effects on embryonic development was
      considered to be 100 mg/kg/day when administered orally by dietary admix.

PMID- 17433520
TI  - Study of the protective effect of ascorbic acid against the toxicity of stannous
      chloride on oxidative damage, antioxidant enzymes and biochemical parameters in
      rabbits.
AB  - Stannous chloride (SnCl2) is a reducing chemical agent used in several man-made
      products. SnCl2 can generate reactive oxygen species (ROS). Therefore, the
      present study has been carried out to investigate the antioxidant action of l
      ascorbic acid (AA) in minimizing SnCl2 toxicity on lipid peroxidation,
      antioxidant enzyme, and biochemical parameters in male New Zealand white rabbits.
      Animals were assigned to one of four treatment groups: 0mg AA and 0mg SnCl2/kg BW
      (control); 40 mg AA/kg BW; 20mg SnCl2/kg BW; 20mg SnCl2 plus 40 mg AA/kg BW.
      Rabbits were orally administered the respective doses every other day for 12
      weeks. Results obtained showed that SnCl2 significantly (P<0.05) induced
      thiobarbituric acid-reactive substances (TBARS; the marker of lipid peroxidation)
      in plasma, while the activities of glutathione S-transferase (GST), superoxide
      dismutase (SOD) and catalase (CAT), and the level of sulfhydryl groups (SH-group)
      were decreased (P<0.05) in blood plasma. Aspartate transaminase (AST), alanine
      transaminase (ALT), alkaline phosphatase (AlP), acid phosphatase (AcP) and
      lactate dehydrogenase (LDH) activities were decreased (P<0.05). Stannous chloride
      significantly (P<0.05) increased the levels of plasma total lipid (TL),
      cholesterol, triglyceride (TG), low-density lipoprotein (LDL) and very low
      density lipoprotein (VLDL), glucose, urea and total bilirubin. On the other hand,
      the level of plasma high-density lipoprotein (HDL), total protein (TP), albumin
      (A) and globulin (G) were significantly (P<0.05) decreased. Ascorbic acid alone
      significantly decreased the levels of TBARS, lipids and urea, and increased the
      activities of GST, SOD and CAT, and the levels of SH-group and proteins. While
      the rest of the tested parameters were not affected. Also, the presence of AA
      with SnCl2 alleviated its harmful effects on most of the tested parameters.
      Therefore, the present results revealed that treatment with AA could minimize the
      toxic effects of stannous chloride.

PMID- 17433521
TI  - Inhibition of human recombinant cytochrome P450s by curcumin and curcumin
      decomposition products.
AB  - Curcumin (diferuloylmethane) is a major yellow pigment and dietary component
      derived from Curcuma longa. It has potent anti-inflammatory, anticarcinogenic,
      antioxidant and chemoprotective activities among others. We studied the
      interactions of curcumin, a mixture of its decomposition products, and four of
      its individually identified decomposition products (vanillin, vanillic acid,
      ferulic aldehyde and ferulic acid) on five major human drug-metabolizing
      cytochrome P450s (CYPs). Curcumin inhibited CYP1A2 (IC(50), 40.0 microM), CYP3A4
      (IC(50), 16.3 microM), CYP2D6 (IC(50), 50.3 microM), CYP2C9 (IC(50), 4.3 microM)
      and CYP2B6 (IC(50), 24.5 microM). Curcumin showed a competitive type of
      inhibition towards CYP1A2, CYP3A4 and CYP2B6, whereas a non-competitive type of
      inhibition was observed with respect to CYP2D6 and CYP2C9. The inhibitory
      activity towards CYP3A4, shown by curcumin may have implications for drug-drug
      interactions in the intestines, in case of high exposure of the intestines to
      curcumin upon oral administration. In spite of the significant inhibitory
      activities shown towards the major CYPs in vitro, it remains to be established,
      whether curcumin will cause significant drug-drug interactions in the liver,
      given the reported low systemic exposure of the liver to curcumin. The
      decomposition products of curcumin showed no significant inhibitory activities
      towards the CYPs investigated, and therefore, are not likely to cause drug-drug
      interactions at the level of CYPs.

PMID- 17433522
TI  - Modulation of hepatic and renal metabolism and toxicity of trichloroethylene and
      perchloroethylene by alterations in status of cytochrome P450 and glutathione.
AB  - The relative importance of metabolism of trichloroethylene (Tri) and
      perchloroethylene (Perc) by the cytochrome P450 (P450) and glutathione (GSH)
      conjugation pathways in their acute renal and hepatic toxicity was studied in
      isolated cells and microsomes from rat kidney and liver after various treatments
      to modulate P450 activity/expression or GSH status. Inhibitors of P450 stimulated
      GSH conjugation of Tri and, to a lesser extent, Perc, in both kidney cells and
      hepatocytes. Perc was a more potent, acute cytotoxic agent in isolated kidney
      cells than Tri but Perc-induced toxicity was less responsive than Tri-induced
      toxicity to modulation of P450 status. These observations are consistent with
      P450-dependent bioactivation being more important for Tri than for Perc.
      Incubation of isolated rat hepatocytes with Tri produced no acute cytotoxicity in
      isolated hepatocytes while Perc produced comparable cytotoxicity as in kidney
      cells. Modulation of P450 status in hepatocytes produced larger changes in Tri-
      and Perc-induced cytotoxicity than in kidney cells, with non-selective P450
      inhibitors increasing toxicity. Induction of CYP2E1 with pyridine also markedly
      increased sensitivity of hepatocytes to Tri but had little effect on Perc-induced
      cytotoxicity. Increases in cellular GSH concentrations increased Tri- and Perc
      induced cytotoxicity in kidney cells but not in hepatocytes, consistent with the
      role of GSH conjugation in Tri- and Perc-induced nephrotoxicity. In contrast,
      depletion of cellular GSH concentrations moderately decreased Tri- and Perc
      induced cytotoxicity in kidney cells but increased cytotoxicity in hepatocytes,
      again pointing to the importance of different bioactivation pathways and modes of
      action in kidney and liver.

PMID- 17433523
TI  - Abundance of aryl hydrocarbon receptor potentiates benzo[a]pyrene-induced
      apoptosis in Hepa1c1c7 cells via CYP1A1 activation.
AB  - Although B[a]P-induced apoptosis has been demonstrated in Hepa1c1c7 cells, the
      cellular signaling pathway(s) by which benzo[a]pyrene (B[a]P) elicits a
      cytotoxicity-mediated apoptogenic role remains to be elucidated. In this study,
      we showed that B[a]P induces apoptosis in a p53-mediated and caspase-3-dependent
      manner, which relates to the accumulation of the S phase of the cell cycle.
      Importantly, we have shown for the first time that Hepa1c1c7 cells retain a
      considerably high content of aryl hydrocarbon receptor (AhR) protein before B[a]P
      exposure, assuming that this status enables the cells to respond to B[a]P more
      readily as well as more efficiently. B[a]P treatment resulted in the
      downregulation of AhR and induced cytochrome P450 1A1 (CYP1A1) (but not
      cytochrome P450 1B1 (CYP1B1)) expression and activity. While alpha-naphtoflavone
      (alpha-NF) and ellipticine suppressed B[a]P-induced CYP1A1 activation as well as
      apoptosis, the 2,3',4,5'-tetramethoxystilbene (TMS) and pyrene, known CYP1B1
      inhibitors, failed to inhibit apoptosis. However, alpha-NF alone significantly
      increased CYP1A1 protein expression but not its activity, suggesting that alpha
      NF more likely works as an AhR agonist in Hepa1c1c7 cells after B[a]P, rather
      than a direct inhibitor of CYP1A1 activity. In conclusion, it is suggested that
      the abundance of endogenous AhR level is an indispensable condition for an
      efficient cellular signaling of B[a]P and that control of AhR activity in
      Hepa1c1c7 cells might be important to cell fate resulting from CYP1A1 activation
      after B[a]P.

PMID- 17433524
TI  - Beyond the intensive care unit: a review of interventions aimed at anticipating
      and preventing in-hospital cardiopulmonary arrest.

PMID- 17433526
TI  - The incidence and significance of emesis associated with out-of-hospital cardiac
      arrest.
AB  - STUDY OBJECTIVE: Studies have suggested that emesis may occur in up to a third of
      cardiac arrest patients. The goal of this investigation was to characterize the
      frequency, timing, and outcome association of emesis in persons suffering out-of
      hospital cardiac arrest in order to understand the role and care-implications of
      emesis better. METHODS: We conducted a cohort study of persons 18 years and over
      suffering non-traumatic out-of-hospital cardiac arrests who received attempted
      resuscitation by paramedics in the study community from January 1, 2004 through
      December 31, 2005 (n=1009). The presence and timing of emesis were determined by
      paramedics and recorded on the Emergency Medical Services report form. We used
      logistic regression analyses to assess whether emesis was independently
      associated with survival to hospital discharge. RESULTS: The presence or absence
      of emesis was documented in 76% (1009/1333) of cases. Emesis was present in 32%
      (318/1009). Two-thirds (208/312) of emesis occurred prior to EMS arrival; 28%
      (88/312) of episodes occurred between EMT arrival and intubation; and 4% (13/312)
      occurred after intubation. After adjustment for potential confounders, the
      presence of emesis was associated with a decreased odds of survival to hospital
      discharge among all-rhythm arrest (Odds ratio (OR)=0.50 [0.28-0.89]) and
      ventricular fibrillation arrest (OR=0.52 [0.27-0.98]). CONCLUSION: Given the
      frequency of emesis, the potential that some portion of emesis may be related to
      care, and the adverse association between emesis and survival, approaches that
      treat or prevent emesis better may improve the chances of survival following out
      of-hospital cardiac arrest.

PMID- 17433527
TI  - The functional organization of the fish olfactory system.
AB  - Recent developments in the functional anatomy and physiology of the fish
      olfactory system reveal three parallel pathways from the sensory epithelium, via
      the olfactory bulb to the telencephalon. There are three morphological types of
      sensory neurones spread in a seemingly overlapping arrangement in the olfactory
      epithelium. The axons of each type of sensory neurones converge to a specific
      region of the olfactory bulb and connect to separate sets of relay neurones. The
      axons of these relay neurones leave in three bundles to the telencephalon. Each
      bundle conveys specific information that elicits sets of characteristic behaviour
      in response to odours involved in essential life processes in the fish. One
      pathway is tuned to social cues, another to sex pheromones, and the third to food
      odours.

PMID- 17433528
TI  - The contribution of apolipoprotein E alleles on cognitive performance and dynamic
      neural activity over six decades.
AB  - Neuroimaging shows brain-functional differences due to apolipoprotein E (APOE)
      polymorphisms may exist decades before the increased risk period for Alzheimer's
      disease, but little is known about their effect on cognition and brain function
      in children and young adults. This study assessed 415 healthy epsilon2 and
      epsilon4 carriers and matched epsilon3/epsilon3 controls, spanning ages 6-65, on
      a range of cognitive tests. Subjects were also compared on a new dynamical
      measure of EEG activity during a visual working memory task using alphabetical
      stimuli. epsilon4 subjects had better verbal fluency compared to epsilon3, an
      effect that was strongest in 51-65 year-olds. No epsilon4 deficits in cognition
      were found. In 6-15 year-olds, there were differences in total spatio-temporal
      wave activity between epsilon3 and epsilon4 subjects in the theta band,
      approximately 200ms post-stimulus. Differences in brain function in younger
      epsilon4 subjects and superior verbal fluency across the entire age range suggest
      that the APOE epsilon4 allele is an example of antagonistic pleiotropy.

PMID- 17433529
TI  - Microwave-assisted stripping of oil contaminated drill cuttings.
AB  - The application of microwave heating technology to conventional gas stripping
      processes has been investigated in the remediation of contaminated drill
      cuttings. The technical feasibility and limitations of nitrogen and steam
      stripping processes are demonstrated, and it is shown that the combination of
      microwave heating with the stripping process offers a step change in performance.
      Order of magnitude improvements in processing time are shown for the microwave
      assisted processes, as well as greatly improved levels of remediation. The
      mechanisms of contaminant removal are discussed, along with the phenomena which
      occur with microwave heating processes. The energy requirements of each of pure
      gas and microwave-assisted processes are also discussed, and the potential
      applications of each technology are highlighted relative to the overall
      remediation requirements.

PMID- 17433530
TI  - Flowrate targeting for threshold problems and plant-wide integration for water
      network synthesis.
AB  - Water reuse/recycle has gained much attention in recent years for environmental
      sustainability reasons, as well as the rising costs of fresh water and effluent
      treatment. Process integration techniques for the synthesis of water network have
      been widely accepted as a promising tool to reduce fresh water and wastewater
      flowrates via in-plant water reuse/recycle. To date, the focus in this area has
      been on water network synthesis problems, with little attention dedicated to the
      rare but realistic cases of so-called threshold problems. In this work, targeting
      for threshold problems in a water network is addressed using the recently
      developed numerical tool of water cascade analysis (WCA). Targeting for plant
      wide integration is then addressed. By sending water sources across different
      geographical zones in plant-wide integration, the overall fresh water and
      wastewater flowrates are reduced simultaneously.

PMID- 17433531
TI  - Testosterone deficiency and prostate cancer: emerging recognition of an important
      and troubling relationship.

PMID- 17433532
TI  - Reducing warm ischaemia time during laparoscopic partial nephrectomy: a
      prospective comparison of two renal closure techniques.
AB  - OBJECTIVE: To test the hypothesis that a modified technique for renal parenchymal
      closure during laparoscopic partial nephrectomy (LPN) enables a significant
      reduction in warm ischaemia (WIT). METHODS: Perioperative factors including WIT
      were prospectively recorded during 40 consecutive LPNs performed by a single
      experienced laparoscopist. In the first 20 (controls), renal parenchyma was
      closed by conventional technique (haemostasis and closure of the collecting
      system with interrupted sutures, then closure of the renal parenchyma over a
      Surgicel bolster before unclamping the renal artery). In the second consecutive
      20 patients (group 1), a modified closure technique was used, which involved
      earlier arterial unclamping after two (group 1a) or one (group 1b) running suture
      on the tumour bed. Vascularised renal parenchyma was then closed over a surgical
      bolster. RESULTS: All LPNs were performed successfully without conversion. WIT
      was significantly less in group 1 compared with the control group (27.2+/-5 min
      vs. 13.7+/-4 min, respectively; p<0.01). WIT was 16.8+/-3.6 vs. 10.3+/-1.2 min in
      groups 1a and 1b (p<0.01); no other significant differences were observed in
      perioperative factors. All specimens had negative tumour margins histologically.
      Major complications and haemoglobin reduction were lower in group 1 compared with
      the control group. CONCLUSIONS: The described technique is effective and allows a
      significant reduction of WIT, even in challenging cases, without increasing
      perioperative bleeding or morbidity. Its use therefore reduces the need for
      hypothermic techniques, and allows more time for careful tumour resection and
      renal reconstruction.

PMID- 17433533
TI  - Quantifying noise-induced stability of a cortical fast-spiking cell model with
      Kv3-channel-like current.
AB  - Population oscillations in neural activity in the gamma (>30 Hz) and higher
      frequency ranges are found over wide areas of the mammalian cortex. Recently, in
      the somatosensory cortex, the details of neural connections formed by several
      types of GABAergic interneurons have become apparent, and they are believed to
      play a significant role in generating these oscillations through synaptic and gap
      junctional interactions. However, little is known about the mechanism of how such
      oscillations are maintained stably by particular interneurons and by their local
      networks, in a noisy environment with abundant synaptic inputs. To obtain more
      insight into this, we studied a fast-spiking (FS)-cell model including Kv3
      channel-like current, which is a distinctive feature of these cells, from the
      viewpoint of nonlinear dynamical systems. To examine the specific role of the Kv3
      channel in determining oscillation properties, we analyzed basic properties of
      the FS-cell model, such as the bifurcation structure and phase resetting curves
      (PRCs). Furthermore, to quantitatively characterize the oscillation stability
      under noisy fluctuations mimicking small fast synaptic inputs, we applied a
      recently developed method from random dynamical system theory to estimate
      Lyapunov exponents, both for the original four-dimensional dynamics and for a
      reduced one-dimensional phase-equation on the circle. The results indicated that
      the presence of the Kv3-channel-like current helps to regulate the stability of
      noisy neural oscillations and a transient-period length to stochastic attractors.

PMID- 17433534
TI  - Duality between decomposition and gluing: a theoretical biology via adjoint
      functors.
AB  - Two ideas in theoretical biology, 'decomposition into functions' and 'gluing
      functions', are formalized as endofunctors on the category of directed graphs. We
      prove that they constitute an adjunction. The invariant structures of the
      adjunction are obtained. They imply two biologically significant conditions: the
      existence of cycles in finite graphs and anticipatory diagrams.

PMID- 17433536
TI  - Reversible toluene adsorption on monolithic carbon aerogels.
AB  - Thirteen monolithic carbon aerogels with different pore textures were used as
      toluene adsorbents. Adsorption was carried out under both static and dynamic
      conditions. Under static conditions at 25 degrees C and at saturation, an
      adsorption capacity as high as 1.36 cm(3) g(-1) or 1180 mg g(-1) was obtained.
      Toluene adsorption was a reversible process in all carbon aerogels, and the
      adsorbed toluene was completely recovered by heating them at 400 degrees C.
      Regenerated adsorbents showed larger surface area and micropore width than the
      original samples, indicating that no pore blockage was produced. Adsorption under
      dynamic conditions at 100 degrees C was also completely reversible after at least
      three consecutive adsorption-desorption cycles. The ability of these carbon
      aerogels to reversibly adsorb toluene could be useful for their application in
      thermal swing adsorption or pressure swing adsorption equipment.

PMID- 17433535
TI  - 14-3-3 sigma increases the transcriptional activity of the androgen receptor in
      the absence of androgens.
AB  - The androgen receptor (AR) is a ligand-activated transcription factor that
      regulates numerous target genes, including prostate-specific antigen (PSA). We
      examined the ability of each member of the 14-3-3 family to modulate
      transcription of PSA through the AR. Despite significant homology within the 14-3
      3 family we observed differences in the ability of each isoform to alter the
      transcriptional activity of the AR. Significantly, 14-3-3 sigma activated PSA
      luciferase reporters not only at castrate levels of androgens, but also in the
      complete absence of androgens. 14-3-3 sigma also increased expression of the
      endogenous PSA gene in the absence of androgens. Knockdown of the AR by siRNA
      oligonucleotides abolished activation of these reporters by 14-3-3 sigma. These
      findings may have greatest significance in hormone refractory prostate cancer
      where the AR may be activated in a ligand-independent manner.

PMID- 17433538
TI  - EMChIE 2006. Proceedings of the 5th European Meeting on Chemical Industry and
      Environment, 3-5 May 2006, Vienna, Austria.

PMID- 17433537
TI  - Simulation of methylene blue adsorption by salts-treated beech sawdust in batch
      and fixed-bed systems.
AB  - Batch and column kinetics of methylene blue adsorption on calcium chloride, zinc
      chloride, magnesium chloride and sodium chloride treated beech sawdust were
      simulated, using untreated beech sawdust as control, in order to explore its
      potential use as a low-cost adsorbent for wastewater dye removal. The adsorption
      capacity, estimated according to Freundlich's model, the Langmuir constant K(L)
      and the adsorption capacity coefficient values, determined using the Bohart and
      Adams' bed depth service model indicate that salts treatment enhanced the
      adsorption properties of the original material. Since sawdust is an industrial
      waste/byproduct and the salts used can be recovered as spent liquids from various
      chemical operations, this process of adsorbent upgrading/modification might be
      considered to take place within an 'Industrial Ecology' framework.

PMID- 17433539
TI  - Flammability limits of isobutane and its mixtures with various gases.
AB  - Flammability limits of isobutane and five kinds of binary mixtures of isobutane
      were measured by the ASHRAE method. Propane, nitrogen, carbon dioxide,
      chloroform, and HFC-125 (1,1,1,2,2-pentafluoroethane) were used as the counter
      part gases in the mixtures. The observed data were analyzed using the equations
      based on Le Chatelier's formula. The flammability limits of mixtures with propane
      were well explained by the original Le Chatelier's formula. The flammability
      limits of mixtures with nitrogen and the ones with carbon dioxide were adequately
      analyzed by the extended Le Chatelier's formula. It was found that the extended
      Le Chatelier's formula is also applicable to the flammability limits of mixtures
      with chloroform and HFC-125.

PMID- 17433540
TI  - Cytoplasmic localization of mPER1 clock protein isoforms in the mouse retina.
AB  - The mammalian Period1 gene is rhythmically expressed and its proteins are found
      within the nucleus of the cells of the suprachiasmatic nuclei (SCN), the central
      circadian pacemaker in mammals; however, whether the target of the PER1 proteins
      is also the nucleus in the retinal peripheral clock cells is yet to be
      determined. Using an anti-PER1 protein antibody in Western blot analyses, we
      found three isoforms (75, 110 and 140kDa) in extracts of the SCN, as well as in
      other different parts of the brain, whereas just two isoforms (75 and 110kDa)
      were detected in the retinal extracts. We have observed that PER1 immunolabelling
      has a cytoplasmic location in many cells of the ganglion cell layer and in a few
      cells in the inner nuclear layer of the mouse retina. This cellular location was
      seen in any of the tissue samples taken at 4h intervals, either in the day/night
      cycle or in constant darkness, of both wild type and rd mice. Unlike this
      situation, PER1 isoforms were nuclear proteins in the SCN cells as well as in
      other parts of the brain of the same animals. No circadian changes were found for
      these clock proteins in the neural retina. These findings suggest that PER1
      proteins play roles in the retina different from those established in the SCN.

PMID- 17433541
TI  - Dysbindin gene variants are associated with bipolar I disorder in a Korean
      population.
AB  - The dysbindin gene (DTNBP1) has been associated with schizophrenia in several
      populations. Because the clinical characteristics of schizophrenia and bipolar
      disorder overlap in many respects and findings from genetic studies have
      suggested common genes between them, we conducted a case control association
      study of bipolar disorder in Korea to investigate the genetic association between
      DTNBP1 and bipolar disorder. In total, 163 patients with bipolar disorder and 350
      controls were evaluated. We genotyped three single nucleotide polymorphisms of
      DTNBP1 (SNP A, P1763, and P1320) and analyzed the allele, genotype, and haplotype
      associations with bipolar disorder. We found significant genotypic associations
      with P1763 and P1320, but no association with SNP A in the bipolar I group. When
      we included bipolar II and schizoaffective disorder in the affected phenotype,
      the significance decreased. A positive association was observed between the SNP A
      P1763 haplotype and the bipolar I phenotype. This haplotype association was lost
      when we either broadened our phenotype or included P1320 in a haplotype. The
      positive results of the present study lost significance after a Bonferroni
      correction for multiple testing. These findings are consistent with previous
      findings that showed a positive association of DTNBP1 with bipolar disorders.
      Moreover, our results suggest that DTNBP1 may contribute more to bipolar I
      disorder than bipolar II disorder or schizoaffective disorder. Further
      comprehensive studies will be required to clarify these association, however, it
      seems likely that DTNBP1 is a susceptibility gene for bipolar disorder.

PMID- 17433542
TI  - Rosuvastatin reduces gliosis and the accelerated weight gain observed in WT and
      ApoE-/- mice exposed to a high cholesterol diet.
AB  - The influence of a high cholesterol (HC) diet on brain pathology is being
      recognized increasingly and is of immense interest. Previous findings from our
      laboratory demonstrated that a high cholesterol diet increases gliosis,
      astrocytic reactivity and neuroinflammation in both wild type (WT) and
      apolipoprotein knockout (ApoE-/-) mice. In the present study, we analyzed whether
      this increase in astrocytic reactivity, monitored by the number of cells in the
      hippocampus labelled with glial fibrillary acidic protein (GFAP), could be
      reduced by the use of rosuvastatin, a potent competitive inhibitor of 3-hydroxy-3
      methylglutaryl-Coenzyme A (HMG-CoA) reductase. Furthermore, we studied the effect
      of rosuvastatin on changes in lipoprotein levels and weight gain, and their
      correlation to gliosis, in mice fed a high cholesterol diet. A significant
      increase in weight, total-cholesterol (TC) and low-density lipoprotein (LDL)
      levels were observed in WT and ApoE-/- mice on a HC diet. The number of GFAP
      labelled cells was found to be significantly increased in mice on a HC diet and
      reduced in rosuvastatin-treated WT and ApoE-/- mice on a HC diet. A significant
      reduction of weight, total-cholesterol and LDL levels was observed in
      rosuvastatin-treated WTHC mice. Significant correlations were found between
      changes in body weight, GFAP labelled cells and plasma total-cholesterol levels
      in WT and ApoE-/- mice. However, the correlations were found to be weaker for the
      GFAP labelled cells in the ApoE-/- mice. The results indicate that the observed
      reduction of gliosis by rosuvastatin treatment may be due to mechanisms that are
      independent of its lipid-lowering effect.

PMID- 17433544
TI  - Haptic selective attention by foot and by hand.
AB  - Nonvisual perceptions of a wielded object's spatial properties are based on the
      quantities expressing the object's mass distribution, quantities that are
      invariant during the wielding. The mechanoreceptors underlying the kind of haptic
      perception involved in wielding - referred to as effortful, kinesthetic, or
      dynamic touch - are those embedded in the muscles, tendons, and ligaments. The
      present experiment's focus was the selectivity of this muscle-based form of
      haptic perception. For an occluded rod grasped by the hand at some intermediate
      position along its length, participants can attend to and report selectively the
      rod's full length, its partial lengths (fore or aft of the hand), and the
      position of the grip. The present experiment evaluated whether participants could
      similarly attend selectively when wielding by foot. For a given rod attached to
      and wielded by foot or attached to (i.e. grasped) and wielded by hand,
      participants reported (by magnitude production) the rod's whole length or
      fractional length leftward of the point of attachment. On measures of mean
      perceived length, accuracy, and reliability, the degree of differentiation of
      partial from full extent achieved by means of the foot matched that achieved by
      means of the hand. Despite their neural, anatomical, and experiential
      differences, the lower and upper limbs seem to abide by the same principles of
      selective muscle-based perception and seem to express this perceptual function
      with equal facility.

PMID- 17433543
TI  - Mangiferin protects against 1-methyl-4-phenylpyridinium toxicity mediated by
      oxidative stress in N2A cells.
AB  - 1-Methyl-4-phenyl-pyridine ion (MPP+), the active metabolite of 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP) induces a Parkinsonian syndrome in humans and
      animals, a neurotoxic effect postulated to derive from oxidative stress. We
      report here the first investigation of MPP+-induced oxidative stress in the
      murine neuroblastoma cell line N2A. Significant cell death was observed following
      exposure to 0.25 mM MPP+. Markers of oxidative stress included decreased
      intracellular levels of GSH after 48 h of exposure (85% depletion) as well as an
      increase in GSSG. Expression of both superoxide dismutase 1 (sod1) and catalase
      (cat) mRNA was increased, as well the activity of catalase. These cellular
      effects were, at least partially, reversed by treatment with the natural
      polyphenol mangiferin. Administration of mangiferin protected N2A cells against
      MPP+-induced cytotoxicity, restored the GSH content (to 60% of control levels),
      and down-regulated both sod1 and cat mRNA expression. Together, these results
      suggest that the protective effect of mangiferin in N2A cells is mediated by the
      quenching of reactive oxygen intermediates. Therefore, mangiferin could be a
      useful compound in therapies for degenerative diseases, including Parkinson's
      disease, in which oxidative stress plays a crucial role.

PMID- 17433545
TI  - Expression of c-Fos protein in the brain after intravenous injection of ghrelin
      in rats.
AB  - In this study, we surveyed central neurons that might be activated after
      peripheral administration of a gut-brain peptide ghrelin, by examining neurons
      expressing c-Fos protein. First, we examined the relationship between the dose of
      ghrelin and the amount of gastric acid secreted. Ghrelin induced a significant
      increase in the amount of gastric acid secretion in a dose-dependent manner.
      Secondly, we examined central neurons that expressed c-Fos protein after
      intravenous injection of ghrelin. We found that intravenously injected ghrelin
      induced the neural expression of c-Fos protein in several nuclei and
      circumventricular organs in the brain. These results suggest that ghrelin
      released into the circulation may stimulate central neurons that have some role
      in the control mechanism for gastric acid secretion.

PMID- 17433547
TI  - Exploring the next neighbourhood relationship in amorphous alloys utilizing atom
      probe tomography.
AB  - A new algorithm is developed to explore the next neighbourhood atomic vicinity
      from the analysed data obtained using the tomographic atom probe (TAP) technique.
      The presented algorithm allows to calculate the atomic distances among different
      next neighbours of different elements as applied to bulk amorphous alloys. The
      results obtained for Pd55 Cu23 P22 bulk amorphous alloys show reasonable
      consistency to already available data from different diffraction techniques. The
      Pd-Pd atoms have highest probability to be a next neighbour than others. The
      established view that P is not a direct next neighbour to each other is also
      manifested from these results. Normalizing the distances of the next neighbours
      to the first neighbour distance in this particular amorphous system possesses a
      definite order for all elemental correlations. Furthermore, the algorithm was
      processed for different critical reconstruction parameters to explore the
      corresponding effect on the distance distribution of next neighbouring atoms. The
      minor changes in the product of the geometric factor and the evaporation field of
      the sample does not make any egregious difference on the next neighbourhood
      evaluation (NNE).

PMID- 17433548
TI  - Control of gastrointestinal nematodes with copper oxide wire particles in a flock
      of lactating Polypay ewes and offspring in Iowa, USA.
AB  - Copper oxide wire particles (COWP) have been used to reduce infection of
      Haemonchus contortus in hair breed lambs in southeastern USA without signs of
      copper toxicity. However, copper sensitivity among breeds and regions varies. The
      objective was to determine the effectiveness and safety of COWP in lactating
      Polypay ewes and their offspring grazing alfalfa/bluegrass pasture in a
      rotational grazing system. Mature Polypay ewes were administered 0, 0.5, 1, or 2
      g (n=8 or 9/dose) COWP approximately 60 days after lambing in mid-July 2005.
      Their offspring were administered 0 (n=6), 0.5 or 0.75 g (n=9), 1 or 2 g (n=6)
      COWP 2 weeks later in late July. The primary gastrointestinal nematode was H.
      contortus (70%). Between Days 7 and 35, FEC were greater in 0 and 0.5 g COWP
      groups compared with ewes administered 2 g COWP (COWP x day, P<0.004). PCV
      decreased in all groups of ewes between Days 0 and 21 (day, P<0.001). Aspartate
      aminotransferase (AST) activity, a measure of liver copper levels, and body
      weight was similar among groups of ewes. FEC decreased within 7 days in COWP
      treated compared with untreated lambs and remained low throughout experiment
      (COWP x day, P<0.05). PCV increased in COWP-treated lambs between Days 7 and 35
      and decreased in untreated lambs between Days 0 and 21 (COWP x day, P<0.009). AST
      activity was similar among groups of lambs. Administration of 2 g COWP to ewes
      prevented a rise in FEC, but a dose of 0.5 g was ineffective as an anthelmintic.
      Administration of all doses of COWP to lambs decreased FEC and increased PCV
      compared to untreated lambs. There were no signs of copper toxicity in ewes or
      lambs. Alternative suppression of H. contortus infections may be necessary in
      ewes, but COWP was effective in H. contortus management for lambs.

PMID- 17433546
TI  - Pharmacological, behavioural and mechanistic analysis of HIV-1 gp120 induced
      painful neuropathy.
AB  - A painful neuropathy is frequently observed in people living with human
      immunodeficiency virus type 1 (HIV-1). The HIV coat protein, glycoprotein 120
      (gp120), implicated in the pathogenesis of neurological disorders associated with
      HIV, is capable of initiating neurotoxic cascades via an interaction with the
      CXCR4 and/or CCR5 chemokine receptors, which may underlie the pathogenesis of HIV
      associated peripheral neuropathic pain. In order to elucidate the mechanisms
      underlying HIV-induced painful peripheral neuropathy, we have characterised
      pathological events in the peripheral and central nervous system following
      application of HIV-1 gp120 to the rat sciatic nerve. Perineural HIV-1 gp120
      treatment induced a persistent mechanical hypersensitivity (44% decrease from
      baseline), but no alterations in sensitivity to thermal or cold stimuli, and
      thigmotactic (anxiety-like) behaviour in the open field. The mechanical
      hypersensitivity was sensitive to systemic treatment with gabapentin, morphine
      and the cannabinoid WIN 55,212-2, but not with amitriptyline. Immunohistochemical
      studies reveal: decreased intraepidermal nerve fibre density, macrophage
      infiltration into the peripheral nerve at the site of perineural HIV-1 gp120;
      changes in sensory neuron phenotype including expression of activating
      transcription factor 3 (ATF3) in 27% of cells, caspase-3 in 25% of cells,
      neuropeptide Y (NPY) in 12% of cells and galanin in 13% of cells and a spinal
      gliosis. These novel findings suggest that this model is not only useful for the
      elucidation of mechanisms underlying HIV-1-related peripheral neuropathy but may
      prove useful for preclinical assessment of drugs for the treatment of HIV-1
      related peripheral neuropathic pain.

PMID- 17433549
TI  - Critical evaluation of the modified-adult immersion test with discriminating dose
      bioassay for Boophilus microplus using American and Australian isolates.
AB  - Similar adult immersion tests (AITs) for acaricide susceptibility of Boophilus
      microplus were done in Texas, USA (Munoz strain) and in Queensland, Australia (N
      strain and Ultimo isolates). Engorged adult female ticks were immersed in one of
      a series of dilutions of commercial acaricide in water and then incubated at room
      temperature for 7 days. Data on oviposition were collected 7 days after exposure
      to acaricide and subjected to probit analysis. For most data, we observed poor
      fit to the probit model. Substantial differences in both LC50 and LC99 for the
      susceptible strains occurred between the respective laboratories and confidence
      intervals for all acaricides and all strains were unacceptably wide. For amitraz,
      the discriminating concentration (double the LC99.9 or LC99) recommended by FAO
      was 0.25%, but our estimates ranged from 0.46% to 9000%. For cypermethrin, the
      recommended DD was 0.0050%, with our estimates ranging from 0.00022% to 0.74%.
      For coumaphos the recommended DD was 0.50% but our estimates ranged from 0.66% to
      130%. Finally, for moxidectin, the recommended DD was 0.10%, while our estimates
      ranged from <0.0001% to 5.9%. The method does not provide a means to discriminate
      between amitraz-susceptible and -resistant, nor between cypermethrin-susceptible
      and -resistant B. microplus.

PMID- 17433550
TI  - Foot burns: epidemiology and management.
AB  - This is a retrospective study of the epidemiology and management of isolated foot
      burns presenting to the Welsh Centre for Burns from January 1998 to December
      2002. A total of 289 were treated of which 233 were included in this study.
      Approximately 40% were in the paediatric age group and the gender distribution
      varied dramatically for adults and children. In the adult group the male:female
      ratio was 3.5:1, however in the paediatric group the male:female ratio was more
      equal (1.6:1). Scald burns (65%) formed the largest group in children and scald
      (35%) and chemical burns (32%) in adults. Foot burns have a complication rate of
      18% and prolonged hospital stay. Complications include hypertrophic scarring,
      graft loss/delayed healing and wound infection. Although isolated foot burns
      represent a small body surface area, over half require treatment as in patients
      to allow for initial aggressive conservative management of elevation and regular
      wound cleansing to avoid complications. This study suggests a protocol for the
      initial acute management of foot burns. This protocol states immediate referral
      of all foot burns to a burn centre, admission of these burns for 24-48 h for
      elevation, regular wound cleansing with change of dressings and prophylactic
      antibiotics.

PMID- 17433551
TI  - Biochemical markers in oncology. Part I: molecular basis. Part II: clinical uses.
AB  - The investigation of the molecular mechanisms involved in carcinogenesis and
      tumor progression has led to the development of numerous biochemical markers.
      Biochemical markers may serve for early prediction of tumor recurrence,
      progression and development of metastases including bone metastases and for
      prediction of response to therapy. Tumor antigens have been used for more than a
      decade and although they have shown promising clinical results, their sensitivity
      and specificity remain limited. A lot of knowledge on the key molecules which
      control cell cycle, apoptosis and angiogenesis has been acquired during recent
      years, but their clinical value remains uncertain. Molecular markers which are
      linked to malignant transformation may provide a non-surgical therapeutic
      approach by targeting these molecules through gene therapy or antisense
      molecules. Because of the complexity of the physiopathogical processes involved
      in tumorogenesis and metastases, we first provide a review on the molecular basis
      of the various tumor markers and then discuss their potential clinical utility
      for the major cancers. The review of the current literature indicates that at the
      exception of a few examples, such as the use of Her-2 to predict response of the
      targeted Herceptin therapy, no single marker is sensitive and specific enough to
      perform an accurate diagnosis, predict disease progression or response to
      treatment. A combination of different biochemical and imaging markers appears to
      be the most promising strategy to monitor patients with cancer.

PMID- 17433552
TI  - Oncology for medical students: a European School of Oncology contribution to
      undergraduate cancer education.
AB  - Worldwide undergraduate cancer medicine is taught in a non-unanimous manner.
      There are frequent overlaps, omissions and discrepancies in the curricula of
      different medical schools concerning oncology teaching. Various attempts for
      possible changes and improvements have been made. Several extra-curriculum
      teaching programmes have been developed in academic European settings in
      collaboration with other scientific bodies. In this paper, we are analyzing the
      educational results from 115 medical students--mostly Europeans--who participated
      in three Oncology Summer Courses (2004, 2005, 2006) organized by European School
      of Oncology in collaboration with the University of Ioannina.

PMID- 17433553
TI  - Distinct expression and subcellular localization patterns of Na+/HCO3-
      cotransporter (SLC 4A4) variants NBCe1-A and NBCe1-B in mouse brain.
AB  - The electrogenic Na+/HCO3- cotransporter (NBCe1) has been identified as a key
      player for regulation of intracellular pH in several cell types. The present
      study was undertaken to determine expression and subcellular localization of the
      NH2-terminal solute carrier (SLC) 4A4 variants NBCe1-A and NBCe1-B in mouse brain
      using variant-specific antibodies by immunohistochemistry and immunoelectron
      microscopy. In addition, distribution of NBCe1 variants and activity-dependent
      regulation was investigated in mouse embryonic day 17.5 (E17.5) hippocampal
      primary cultures in vitro. The results showed NBCe1-A and NBCe1-B transcript
      expression in the mouse olfactory bulb, cerebral cortex, hippocampus and
      cerebellum. NBCe1-A was predominantly expressed in Purkinje cells, granule cells
      of the dentate gyrus, non-pyramidal cell bodies in cerebral cortex, and in
      periglomerular and mitral cells in the olfactory bulb. Pyramidal neurons in
      cerebral cortex and apical cell dendrites in the hippocampus were stained for
      both NBCe1-A and NBCe1-B. Moreover, NBCe1-B was present in Bergmann glia. At the
      ultrastructural level, NBCe1-B was preferentially expressed in perivascular
      astroglial lamellae, whereas both NBCe1 NH2-terminal variants were localized in
      pre- and postsynaptic compartments. Except for the olfactory bulb, NBCe1-A was
      always colocalized with calbindin. Treatment of E17.5 primary hippocampal
      cultures with KCl, showed dramatic downregulation of NBCe1-B mRNA and protein
      after 60 min, whereas NBCe1-A expression remained unchanged. These data
      demonstrate for the first time distinct cellular distribution of NBCe1 NH2
      terminal variants in mouse brain. NBCe1 may be involved in neuronal modulation,
      and pH regulation during neuronal activity.

PMID- 17433554
TI  - Estrogen limits ischemic cell death by modulating caspase-12-mediated apoptotic
      pathways following middle cerebral artery occlusion.
AB  - Estrogen has received considerable attention as a potential therapeutic agent
      against various forms of neurodegenerative diseases including stroke.
      Experimental data in animal models of stroke have provided exhaustive evidence of
      the neuroprotective properties of this steroid hormone. Our laboratory in
      particular has demonstrated that acute estrogen treatment in male rats
      significantly reduced (approximately 50%) ischemic cell death within 4 h
      following permanent occlusion of the middle cerebral artery occlusion (MCAO).
      However, the cellular and molecular mechanisms implicated in the protective
      actions of estrogen in this experimental model have yet to be elucidated.
      Accumulating evidence suggests that in various in vivo and in vitro models,
      estrogen can be pro-apoptotic and that this effect may be mediated by an estrogen
      induced up-regulation of the Fas/FasL system and the subsequent activation of
      caspase-12. We therefore hypothesized that under ischemic conditions following
      MCAO, estrogen would up-regulate protective endoplasmic reticulum (ER) stress
      pathways leading to caspase-12 activation, thus limiting infarct volume. Our
      results showed that estrogen significantly increased activated caspase-12 at 2, 3
      and 4 h post-MCAO. Immunostaining of brain sections showed a significantly higher
      number of terminal deoxynucleotidyl transferase-mediated deoxyuridine
      triphosphate nick end-labeling positive cells in estrogen-treated animals at 4 h,
      but not at 2 h, post-MCAO. These findings correlate with previous observations
      that differences in infarct volume between saline and estrogen-treated animals
      are not seen until 3 and 4 h post-MCAO. A decrease in m-calpain expression was
      observed in the infarct region only at 4 h post-MCAO following estrogen pre
      treatment, suggesting m-calpain may not be involved in regulating estrogen
      induced caspase-12 activation. Based on these cellular changes correlated to
      estrogen pretreatment, we conclude that estrogen may up-regulate ER-specific
      apoptotic pathways, thus limiting the extent of necrotic cell death which is
      responsible for the spreading depression and growth of the infarct volume
      following MCAO.

PMID- 17433555
TI  - Stress induced morphological microglial activation in the rodent brain:
      involvement of interleukin-18.
AB  - The present study investigated the possibility that acute stress might activate
      microglial cells. Wistar rats were exposed to 2 h period of restraint combined
      with water immersion stress prior to brain analysis by immunohistochemistry with
      OX-42, a marker of complement receptor CR3. A single session of stress provoked
      robust morphological microglial activation in the thalamus, hypothalamus,
      hippocampus, substantia nigra and central gray. These effects appeared as early
      as at 1 h of exposure and were further intensified at 2 h. Morphological
      activation was not accompanied with changes in markers of functional activation
      or of inflammation including interleukin-1beta (IL-1beta), interleukin-6 (IL-6)
      and inducible nitric oxide synthase (iNOS). Similar results were obtained with
      mice where the effects of stress were compared in animals null for interleukin-18
      (IL-18 KO), a cytokine previously demonstrated to be modulated by stress and to
      contribute to microglia activation. The results demonstrated significant
      reduction of stress-induced microglial activation in IL-18 KO mice. The present
      study reports evidence that physical/emotional stress may induce morphological
      microglial activation in the brain and this activation is in part mediated by
      interleukin-18.

PMID- 17433558
TI  - Opposite effects of maternal separation on intermale and maternal aggression in
      C57BL/6 mice: link to hypothalamic vasopressin and oxytocin immunoreactivity.
AB  - Early life stress, in particular child abuse and neglect, is an acknowledged risk
      factor for the development of pathological anxiety and aggression. In rodents, 3
      h daily maternal separation (MS) during the first 2 weeks of life is an
      established animal model of early life stress and has repeatedly been shown to
      increase anxiety and stress responsiveness in adulthood. However, preclinical
      studies on the effects of postnatal stress on adult aggression are limited. The
      present study investigated whether MS affects intermale aggression and/or
      maternal aggression in C57BL/6 mice. In both adult male and virgin female mice,
      MS elevated anxiety-related behavior as tested on the elevated plus-maze, in the
      open field and during novel object exploration. The latency to attack an unknown
      male intruder, as assessed with the resident-intruder test, was significantly
      longer in MS male mice compared with control male mice. In contrast, the latency
      to attack a novel male intruder was significantly shorter in MS females compared
      with control females on days 3 and 5 of lactation. These opposite effects of MS
      can be explained by the fact that intermale and maternal aggression are two
      different forms of aggression, and hence, might be modulated by different
      neurobiological pathways. Indeed, in the paraventricular nucleus of the
      hypothalamus, MS was found to selectively increase vasopressin immunoreactivity
      in males, whereas MS selectively decreased oxytocin immunoreactivity in lactating
      females. In conclusion, MS has long-lasting and differential effects on adult
      intermale and maternal aggression in C57BL/6 mice. Alterations in hypothalamic
      vasopressin and oxytocin immunoreactivity may, in part, underlie the opposite
      effects of MS on intermale and maternal aggression. The MS paradigm represents a
      promising animal model to reveal underlying mechanisms of aggressive behavioral
      dysfunctions associated with early life stress.

PMID- 17433557
TI  - Evidence for altered hypothalamus-pituitary-adrenal axis functioning in systemic
      hypertension: blunted cortisol response to awakening and lower negative feedback
      sensitivity.
AB  - BACKGROUND: Hypothalamus-pituitary-adrenal (HPA) axis functioning in systemic
      hypertension is not fully understood. We explored HPA axis activity and feedback
      sensitivity to oral administration of dexamethasone in systemic hypertension via
      assessment of the cortisol awakening response (CAR) and the circadian cortisol
      profile. METHODS: The CAR and circadian cortisol profile were assessed in 20
      unmedicated and otherwise healthy middle-aged hypertensive men and in 22
      normotensive male controls. Salivary free cortisol measures for the CAR were
      obtained immediately after awakening and 15, 30, 45, and 60 min thereafter.
      Circadian cortisol secretion was sampled at 08:00, 11:00, 15:00, and 20:00 h.
      Assessment of the CAR was repeated on the next day after administration of 0.5mg
      dexamethasone at 23:00 h on the previous night. RESULTS: Hypertensives had a
      significantly lower CAR (p<0.02) and significantly reduced suppression of the CAR
      after dexamethasone administration (p<0.01) than normotensive controls. There
      were no significant differences in cortisol levels at awakening and in circadian
      cortisol profiles between hypertensives and normotensives. CONCLUSION: We found
      evidence for altered HPA axis activity in men with systemic hypertension evident
      with the CAR. Hypertensives showed relative attenuation in the CAR and in the HPA
      axis feedback sensitivity following dexamethasone suppression. Such alterations
      in HPA axis regulation might contribute to the atherosclerotic risk in
      hypertensive individuals.

PMID- 17433559
TI  - Gut osmolarity: a key environmental cue initiating the gastrointestinal phase of
      Listeria monocytogenes infection?
AB  - In addition to the severe invasive systemic disease of listeriosis, recent
      evidence suggests that the Gram-positive intracellular bacterial pathogen
      Listeria monocytogenes is also a causative agent of febrile gastroenteritis. We
      examined the listerial response to stresses normally encountered in the upper
      small intestine and demonstrate that osmotic stress appears to be at the top of
      the hierarchy of stress responses during gastrointestinal residence. Furthermore,
      we suggest that the increased osmolarity of the gastrointestinal lumen may be
      interpreted as an environmental cue signalling gut entry and that the underlying
      genetic element governing this response is the alternative stress sigma factor
      sigma(B).

PMID- 17433556
TI  - Status epilepticus causes a long-lasting redistribution of hippocampal
      cannabinoid type 1 receptor expression and function in the rat pilocarpine model
      of acquired epilepsy.
AB  - Activation of the cannabinoid type 1 (CB1) receptor, a major G-protein-coupled
      receptor in brain, acts to regulate neuronal excitability and has been shown to
      mediate the anticonvulsant effects of cannabinoids in several animal models of
      seizure, including the rat pilocarpine model of acquired epilepsy. However, the
      long-term effects of status epilepticus on the expression and function of the CB1
      receptor have not been described. Therefore, this study was initiated to evaluate
      the effect of status epilepticus on CB1 receptor expression, binding, and G
      protein activation in the rat pilocarpine model of acquired epilepsy. Using
      immunohistochemistry, we demonstrated that status epilepticus causes a unique
      "redistribution" of hippocampal CB1 receptors, consisting of specific decreases
      in CB1 immunoreactivity in the dense pyramidal cell layer neuropil and dentate
      gyrus inner molecular layer, and increases in staining in the CA1-3 strata oriens
      and radiatum. In addition, this study demonstrates that the redistribution of CB1
      receptor expression results in corresponding functional changes in CB1 receptor
      binding and G-protein activation using [3H] R+-[2,3-dihydro-5-methyl-3
      [(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl](1-napthalen
      yl)methanone mesylate (WIN55,212-2) and agonist-stimulated [35S]GTPgammaS
      autoradiography, respectively. The redistribution of CB1 receptor-mediated
      [35S]GTPgammaS binding was 1) attributed to an altered maximal effect (Emax) of
      WIN55,212-2 to stimulate [35S]GTPgammaS binding, 2) reversed by the CB1 receptor
      antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl
      1H-pyrazole-3-carboxamide hydrochloride (SR141716A), 3) confirmed by the use of
      other CB1 receptor agonists, and 4) not reproduced in other G-protein-coupled
      receptor systems examined. These results demonstrate that status epilepticus
      causes a unique and selective reorganization of the CB1 receptor system that
      persists as a permanent hippocampal neuronal plasticity change associated with
      the development of acquired epilepsy.

PMID- 17433560
TI  - Amelioration of osteoarthritis by intra-articular hyaluronan synthase 2 gene
      therapy.
AB  - Osteoarthritis (OA) is a chronic, degenerative disorder of multifactorial
      aetiology, characterized by loss of articular cartilage and periarticular bone
      remodelling. Goals of managing OA include controlling pain, maintaining and
      improving function and health-related quality of life, and limiting functional
      impairment. Although several managements had been proved to ameliorate the
      symptoms of osteoarthritis, no methods could cure it thoroughly. High-molecular
      weight hyaluronan (HMW-HA) is a major component of synovial joint fluids which
      physically acts as a viscous lubricant for slow joint movements and as an elastic
      shock absorber during rapid movements. It also has a variety of biologic effects
      in vivo, such as inhibiting the release of inflammatory factors and suppressing
      the degradation of cartilage matrix. Intra-articular injection of synthetic HMW
      HA has been used as viscosupplement for knee OA and its therapeutic efficacy has
      been verified. However, repeated injections of HMW-HA which is needed to control
      symptoms increase the probability of infection and sometimes there will have
      acute joint pain with effusion, which requires aspiration to exclude sepsis. In
      order to overcome the disadvantages of repeated injections of HMW-HA, novel
      strategies should be developed. As HMW-HA is synthesized by hyaluronan synthase-2
      (HAS2), we postulate that HAS2 gene could be delivered into intra-articular cells
      by methods of gene therapy to achieve long-lasting synthesis of HMW-HA. In our
      opinion, this strategy seems to hold interesting future prospects for the
      treatment of OA.

PMID- 17433561
TI  - Flavonoids as potential therapeutic agents for type 1 diabetes.

PMID- 17433562
TI  - The coming problem of HIV-associated Alzheimer's disease.
AB  - BACKGROUND: Dementia associated with human immunodeficiency virus (HIV) is a
      subcortical neuropathology that does not resemble Alzheimer's disease. However,
      several lines of evidence suggest that in the future there may be significant
      numbers of long-term HIV survivors with true Alzheimer's disease. Age is itself a
      risk factor Alzheimer's disease, and an aging population and widespread use of
      highly active antiretroviral therapy (HAART) means more elderly HIV patients.
      Immune reconstitution inflammatory syndrome, lypodystrophic effects of HAART
      medications, HIV-induced amyloid deposition and excitotoxic effects of gp120 and
      TAT protein all could be risk factors for subsequent Alzheimer's disease.
      Finally, HIV patients will have greater vulnerability to common non-HIV pathogens
      that may contribute to development of Alzheimer's disease. PRESENTATION OF THE
      HYPOTHESIS: It is predicted that in the future there will be seen measurable
      numbers of long-term HIV survivors on HAART who have Alzheimer's disease, with a
      cortical deficit profile on neuropsychological tests, pronounced cerebral atrophy
      seen on brain MRI, and neurofibrillary tangles, senile plaques and neuronal loss
      in post-mortem brain tissue. VALIDATING THE HYPOTHESIS: The hypothesis could be
      validated through case reports, longitudinal clinical studies, brain bank
      programs and animal models. IMPLICATIONS OF THE HYPOTHESIS: Management of HIV may
      become more difficult, requiring greater provisions for long-term care of HIV
      patients with chronic dementia. However, it may be possible to reduce or prevent
      HIV-associated Alzheimer's disease through early use of cholinesterase
      inhibitors, glutamate-blocking drugs, insulin sensitizing agents, statins and
      anti-oxidants.

PMID- 17433563
TI  - Activation of adventitial fibroblasts contributes to the early development of
      atherosclerosis: a novel hypothesis that complements the "Response-to-Injury
      Hypothesis" and the "Inflammation Hypothesis".
AB  - The role of the adventitia in vascular function and vascular lesion formation has
      been largely ignored. This article introduces the hypothesis that the activation
      of the adventitia, specifically the fibroblasts, contributes to the formation of
      intimal atherosclerotic lesions. The evidence for this hypothesis includes: (a)
      the early proliferative changes seen in fibroblasts found in the adventitia; (b)
      the increase and the alteration of extracellular matrix deposition in the
      adventitia; (c) fibroblast differentiation into myofibroblasts and migration into
      the intima; and (d) fibroblast synthesis and release of cytokines that have
      potent effects on neighboring smooth muscle and endothelial cells prior to
      intimal lesion formation. In conclusion, the activation of adventitial
      fibroblasts is a key regulator of vascular function and structure from the
      "outside-in" and contributes to the development of atherosclerotic lesions. The
      outer location of the adventitia makes it a suitable location for drug delivery
      and gene therapy aimed at preventing and treating atherosclerosis.

PMID- 17433564
TI  - Will Descemet's stripping with automated endothelial keratoplasty (DSAEK) lower
      the rates of allograft rejection in corneal transplants for endothelial failure?
AB  - BACKGROUND: Allograft corneal rejection occurs in a substantial number of full
      thickness transplants in spite of the relative immune privilege enjoyed by the
      cornea. Compared to other layers of the cornea, endothelial rejection has most
      disastrous consequences on graft survival. In the last few years, a new
      technique, Descemet's stripping with automated endothelial keratoplasty (DSAEK)
      is being used of selective transplantation of the endothelium. It involves
      stripping diseased endothelium (and Descemet's) and replacing it by a small
      lamella fashioned from a cadaveric donor cornea, which consists of endothelium,
      Descemet's membrane and a part of posterior stoma. HYPOTHESIS: We hypothesize
      that DSAEK might substantially reduce the incidence of allograft immune rejection
      in corneal transplant done for cases with endothelial failure. EVALUATION OF THE
      HYPOTHESIS: In published reports of consisting of more than 300 surgeries and
      three years experience with DSAEK, no case of graft rejection has been reported.
      In our opinion, this advantage of DSAEK compared to conventional full thickness
      keratoplasty could be due to four factors: (a) The transplanted tissue is placed
      in the anterior chamber and has no exposure to the surface, where the antigen
      presenting cells (APC) and antibodies are present. (b) Significant reduction in
      the number of sutures connecting the host and donor tissue may lead to lesser
      suture related rejection episodes. (c) Absence of direct contact between the host
      stroma vessels and the transplanted tissue disrupts the immune affecter and
      effecter arcs. (d) Reduced immunogenicity of the donated tissue due to absence of
      epithelium. CONSEQUENCES OF THE HYPOTHESIS: If this hypothesis stands true in
      subsequent studies, it could lead to substantial reduction in the socioeconomic
      resources involved in management of graft rejection. Even if this hypotheses
      fails the test of well controlled studies, this would broaden the current
      understanding of the ocular immunology and the immune privilege with which the
      anterior chamber of the eye is normally associated with.

PMID- 17433565
TI  - Conversion of red bone marrow into yellow - Cause and mechanisms.
AB  - Marrow cavities in all the bones of newborn mammals contain active hematopoietic
      tissue, known as red bone marrow. From the early postnatal period onwards, the
      hematopoietic tissue, mainly in the bones of the extremities, is gradually
      replaced by non-hematopoietic mesenchymal cells that accumulate lipid drops,
      known as yellow or fatty bone marrow. For its maintenance, hematopoietic tissue
      depends on the support of special mesenchymal cells in the bone marrow cavity,
      known as hematopoietic microenvironment. Both bone-forming cells and
      hematopoietic microenvironment cells have common progenitors - mesenchymal stem
      cells (MSCs). We hypothesize that: (1) Hematopoietic microenvironment cells
      advance along a three stage differentiation/maturation pathway. In the first
      stage, they support hematopoiesis and contain no fat. In the second stage, cells
      accumulate fat and no longer support steady state hematopoiesis; however, under
      conditions of increased hematopoietic requirement, they lose fat and regain their
      ability to support hematopoiesis. In the last stage, hematopoietic
      microenvironment cells retain the appearance of yellow bone marrow and do not
      support hematopoiesis regardless of the state of hematopoietic requirement.(2)
      Since MSCs are bound to endosteal and trabecular surfaces, in tubular bones their
      number is relatively small, compared to cancellous bones that have much larger
      areas of internal bone surface. MSCs are exposed to proliferative and
      differentiative pressures, leading to gradual reduction of their number.
      Consequently, the MSC population in tubular bones becomes exhausted rather early,
      and the post-maturation compartment of mesenchymal cells finally consists of
      unipotential bone precursors maintaining bone tissue and hematopoietic
      microenvironment advancing towards the last (fatty) stage of differentiation. In
      contrast, in cancellous bones the relatively large number of MSCs does not suffer
      exhaustion and continues to provide newly differentiated hematopoietic
      microenvironment, thus maintaining red bone marrow throughout the organism's
      life.(3) Osteogenic and hematopoietic microenvironment differentiation pathways
      compete with each other for their common precursor. During the organism's growth
      period osteogenic stimuli prevail, while in the post-maturation period, MSC
      differentiation into hematopoietic microenvironment increases at the expense of
      differentiation into bone. This results in the reduction of bone volume and
      expansion of marrow cavities in hematopoietically active cancellous bones, but
      not in tubular bones already depleted of MSCs and not participating in
      hematopoiesis. Experimental and clinical data supporting these hypotheses are
      discussed.

PMID- 17433566
TI  - The interaction of age and hormone replacement therapy on colon adenoma risk.
AB  - BACKGROUND: Several studies have identified a possible interaction between age
      and hormone replacement therapy on colon neoplasm risk. We re-evaluated this
      interaction and determined if this interaction may be explained by the longer
      duration of estrogen use in older, rather than younger, women. METHODS: Included
      in the case-control study were 755 women (169 cases and 586 controls.) who were
      recruited from patients with no prior history of colorectal neoplasm and
      undergoing an elective colonoscopy examination. RESULTS: There was a significant
      interaction between age and hormone replacement therapy use (P=0.03) with current
      estrogen users who were over 56 years of age having a reduced odds of colon
      adenoma (OR, 0.40; 95% CI, 0.16-0.98) when compared to never users. Both older
      women who had used hormone replacement therapy for 3 or less years (OR, 0.07; 95%
      CI, 0.006-0.81) and those reporting greater than 10 years of use (OR, 0.27; 95%
      CI, 0.09-0.80) had a reduced adjusted odds for adenomas when compared to non
      users. No apparent association with estrogen replacement therapy was found among
      younger women (<56 years). CONCLUSIONS: Duration of use is not likely to explain
      the stronger association of hormone replacement therapy use with colon neoplasm
      in older women. Additional work is needed to better characterize the underlying
      mechanisms associated with this interaction.

PMID- 17433567
TI  - [A Longitudinal study of body composition and basal metabolic rate during
      pregnancy in a black population of Kinshasa, Democratic Republic of Congo (RDC)].
AB  - OBJECTIVE: A longitudinal study of body composition and basal metabolic rate
      during pregnancy in a black population of Kinshasa. MATERIALS AND METHODS: Body
      composition and basal metabolic rate were determined by bioimpedance, and energy
      intake was evaluated using the 24 h recall method at 20, 34 and > 37 weeks of
      gestation in 76 black, Congolese women. The subjects had to be healthy, and to
      deliver term, singleton infants after a normal pregnancy. RESULTS: At 20 weeks of
      pregnancy, the 76 women, aged 28.5+/-6.4 years, had a body weight of 61.1+/-7.7
      kg, a body mass index of 23.0+/-3.8 kg/m(2), a fat mass of 36.6+/-6.8% and a
      basal metabolic rate of 1399+/-84 kcal/24 h. Subsequently, increases in body
      weight (+6.5 kg), fat-free mass (+ 5.1 kg), body water (+4.4 l) and basal
      metabolic rate (+297 kcal/24 h) (P < 0.0001) were observed. The increase in fat
      mass (+1.4 kg) was less pronounced. Energy intake was stable. CONCLUSION: Changes
      in body composition during pregnancy in Congolese black women are comparable to
      those reported in other populations. Pre- and per-gravidic fat mass is higher in
      congolese women than in Caucasian women.

PMID- 17433568
TI  - Making equine learning research applicable to training procedures.

PMID- 17433569
TI  - Imprinting training and conditioned taste aversion.

PMID- 17433570
TI  - Training and long-term memory of a novel food acquisition task in a turtle
      (Pseudemys nelsoni).
AB  - We developed a shaping procedure for training Florida red-bellied cooters,
      Pseudemys nelsoni, to dislodge clear plastic bottles to obtain food pellets. The
      animals were then trained in a 2-choice problem to choose only the bottle
      containing pellets. All nine turtles learned the task of knocking over bottles
      for food. For the discrimination task, turtles chose the correct bottle 71% on
      average. After 2 months (82-84 days), and again after another 7.5 months (228
      days) of no interaction with the bottles, turtles were retested and many retained
      both the response and the discrimination (mean success rates 77-81%), with
      significant savings in retraining all turtles. The turtles showed two basic
      response strategies, which changed across time for some individuals. This study
      demonstrates that turtles can learn and retain a novel skill in a laboratory
      context.

PMID- 17433572
TI  - Inhalant use and suicidality among incarcerated youth.
AB  - Studies consistently indicate that inhalant use is associated with increased
      mental health problems in adolescents, but few investigations have focused on the
      potential relationship of inhalant use to suicidality (ideation or attempt). This
      study examined how different levels of volatile solvent use relate to suicidal
      ideation and attempted suicide among 723 incarcerated youth (mean age=15.5,
      S.D.=1.2; 87% male) in Missouri, and whether any associations between solvent use
      and suicidality differ by gender. In bivariate analyses, severity of inhalant use
      was positively associated with histories of suicidal ideation and suicide attempt
      for both boys and girls. In multivariate analyses, inhalant use disorders
      remained significantly associated with suicidal ideation and suicide attempt
      histories even after adjusting for general level of psychiatric symptoms, prior
      trauma, other substance use, gender, and additional potential confounders.
      Inhalant use without abuse or dependence also significantly related to suicidal
      ideation in multivariate analyses, but an interaction between gender and inhalant
      use signified this relationship was stronger for girls. Inhalant use disorders in
      incarcerated youth, as well as inhalant use without abuse or dependence
      (particularly in girls), may signal elevated suicide risk. Suicide risk
      assessments should, therefore, include questions about inhalation of volatile
      solvents such as paint, gasoline, and household cleaners.

PMID- 17433571
TI  - Antisocial behavioral syndromes and DSM-IV drug use disorders in the United
      States: results from the National Epidemiologic Survey on Alcohol and Related
      Conditions.
AB  - BACKGROUND: Antisocial behavioral syndromes, including antisocial personality
      disorder (ASPD), syndromal adult antisocial behavior (AABS) without conduct
      disorder (CD) before age 15, and CD without progression to ASPD ("CD only") are
      highly comorbid with drug use disorders (DUDs). Among patients in DUD treatment,
      antisocial syndromes are associated with greater severity and poorer outcomes.
      Comparative data concerning associations of antisocial syndromes with clinical
      characteristics of DUDs among general population adults have not previously been
      available. This study describes associations of antisocial syndromes with
      clinical characteristics of lifetime Diagnostic and Statistical Manual-Version IV
      DUDs in the general U.S. adult population. METHODS: This report is based on the
      2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions
      (n=43,093, response rate=81%). Respondents (n=4068) with lifetime DUDs were
      classified according to whether they met criteria for ASPD, AABS, "CD only," or
      no antisocial syndrome. Associations of antisocial syndromes with clinical
      characteristics of DUDs were examined using logistic regression. RESULTS:
      Antisocial syndromes were significantly associated with the phenomenology of
      DUDs, particularly ASPD with the most severe clinical presentations. Associations
      with AABS were similar to those with ASPD; those with "CD only" were weak,
      inconsistent, and not statistically significant. Patterns of associations
      differed little between men and women. CONCLUSIONS: Both ASPD and AABS, but not
      "CD only," appear to identify greater clinical severity of DUDs among adults in
      the general U.S. population.

PMID- 17433573
TI  - Tightly regulated, high-level expression from controlled copy number vectors
      based on the replicon of temperate phage N15.
AB  - A new Escherichia coli host/vector system has been developed to allow a dual
      regulation of both the plasmid copy number and gene expression. The new pN15E
      vectors are low copy number plasmids based on the replicon of temperate phage
      N15, comprising the repA replicase gene and cB repressor gene, controlling the
      plasmid copy number. Regulation of pN15E copy number is achieved through
      arabinose-inducible expression of phage N15 antirepressor protein, AntA, whose
      gene was integrated into the chromosome of the host strain under control of the
      PBAD promoter. The host strain also carried phage N15 partition operon, sop,
      allowing stable inheritance of pN15E vectors in the absence of selection
      pressure. In the first vector, pN15E4, the same PBAD promoter controls expression
      of a cloned gene. The second vector, pN15E6, carries the phage T5 promoter with a
      double lac operator repression module thus allowing independent regulation of
      promoter activity and copy number. Using the lacZ gene to monitor expression in
      these vectors, we show that the ratio of induction/repression can be about 7600
      fold for pN15E4 and more than 15,000-fold for pN15E6. The low copy number of
      these vectors ensures very low basal level of expression allowing cloning genes
      encoding toxic products that was demonstrated by the stable maintenance of a gene
      encoding a restriction endonuclease in pN15E4. The tight control of transcription
      and the potential to regulate gene activities quantitatively over wide ranges
      will open up new approaches in the study of gene function in vivo and controlled
      expression of heterologous genes.

PMID- 17433574
TI  - Sequence and structural aspects of the functional diversification of plant
      alcohol dehydrogenases.
AB  - The glycolytic proteins in plants are coded by small multigene families, which
      provide an interesting contrast to the high copy number of gene families studied
      to date. The alcohol dehydrogenase (Adh) genes encode glycolytic enzymes that
      have been characterized in some plant families. Although the amino acid sequences
      of zinc-containing long-chain ADHs are highly conserved, the metabolic function
      of this enzyme is variable. They also have different patterns of expression and
      are submitted to differences in nonsynonymous substitution rates between gene
      copies. It is possible that the Adh copies have been retained as a consequence of
      adaptative amino acid replacements which have conferred subtle changes in
      function. Phylogenetic analysis indicates that there have been a number of
      separate duplication events within angiosperms, and that genes labeled Adh1, Adh2
      and Adh3 in different groups may not be homologous. Nonsynonymous/synonymous
      ratios yielded no signs of positive selection. However, the coefficients of
      functional divergence (theta) estimated between the Adh1 and Adh2 gene groups
      indicate statistically significant site-specific shift of evolutionary rates
      between them, as well as between those of different botanical families,
      suggesting that altered functional constraints may have taken place at some amino
      acid residues after their diversification. The theoretical three-dimensional
      structure of the alcohol dehydrogenase from Arabis blepharophylla was constructed
      and verified to be stereochemically valid.

PMID- 17433575
TI  - Identification of new subgroup of HSP70 in Bythograeidae (hydrothermal crabs) and
      Xanthidae.
AB  - Crabs of the Bythograeidae family (Crustacea: Brachyura: Bythogreoidea) are the
      only endemic crab family living in hydrothermal fields. The hydrothermal
      environment is characterized by unique ecological parameters, such as the high
      temperature gradient around the hydrothermal chimney (2-350 degrees C), a fluid
      environment containing high levels of metals and numerous gases. The 70-kDa Heat
      Shock Protein (HSP70) group is the most-studied HSP, because it is ubiquitous,
      and a strong positive correlation has been found between the amounts of HSP70
      produced in response to stress, and the ability of the organism to withstand
      stressful conditions. The 70-kDa heat shock protein genes from Bythograeids
      (species analyzed: Bythograea thermydron, Cyanagraea praedator and Segonzacia
      mesatlantica) were characterized. Our results revealed that Bythograeidae possess
      genes which are similar with those present in Xanthids (coastal crabs). The
      deduced protein sequences displayed motifs distinct from those in the other
      crustacean HSC70/HSP70s available in the databases. Phylogenetic analysis showed
      that these members of HSP70 family identified in Bythograeidae and Xanthidae
      constitute a new subgroup within this family.

PMID- 17433576
TI  - The complete nucleotide sequence of the mitochondrial genome of the oriental
      fruit fly, Bactrocera dorsalis (Diptera: Tephritidae).
AB  - The complete mitochondrial genome of the oriental fruit fly Bactrocera dorsalis
      s.s. has been sequenced, and is here described and compared with the homologous
      sequences of Bactrocera oleae and Ceratitis capitata. The genome is a circular
      molecule of 15,915 bp, and encodes the set of 37 genes generally found in animal
      mitochondrial genomes. The structure and organization of the molecule is typical
      and similar to the two closely related species B. oleae and C. capitata, although
      it presents an interesting case of putative intra-molecular recombination. The
      relevance of the growing comparative dataset of tephritid complete mitochondrial
      genomes is discussed in relation to the possibility to develop robust assays for
      species discrimination in quarantine and agricultural monitoring practices, as
      well as basic phylogeography/population genetic studies.

PMID- 17433577
TI  - The effect of a prebiotic supplemented formula on growth and stool microbiology
      of term infants.
AB  - BACKGROUND: The intestinal flora of breast-fed infants is generally dominated by
      bifidobacteria which have beneficial properties. Their presence is due to various
      compounds of breast milk including prebiotic substances. AIM: This prospective,
      double blind, study compared the growth, acceptability and the proportion of
      bifidobacteria and clostridia in the stool flora of bottle-fed infants randomized
      to receive a formula with a specific mixture of 0.4 g/100 ml prebiotic galacto-
      and long-chain fructooligosaccharides or the same formula without added
      prebiotics. METHODS: Within 0-14 days after birth at term, healthy bottle-fed
      infants were enrolled to receive either a prebiotic formula or a standard
      formula. At recruitment anthropometric measurements were done. These were
      repeated at the age of 6 and 12 weeks. Stool samples were taken at inclusion and
      at the age of 6 weeks. The number of bifidobacteria and clostridia was determined
      by fluorescent in situ hybridization. RESULTS: There was good tolerance of the
      prebiotic formula. Somatic growth was similar in the two groups. Stool frequency
      was significantly higher in the prebiotic group (P=0.031). Infants in the
      prebiotic group had also softer stools as compared to the control group
      (P=0.026). Baseline values of microorganisms at study entry were similar. The
      percentage of faecal clostridia at the completion of the study was significantly
      lower in the prebiotic group (P=0.042), while the proportion of faecal
      bifidobacteria was higher in the prebiotic group as compared to the control
      group. However this difference did not reach statistical significance (P=0.262).
      The percentage of E. coli was lower in the prebiotic group but again this did not
      reach statistical significance (P=0.312). CONCLUSION: An infant formula
      containing prebiotic oligosaccharides is well tolerated, leads to normal somatic
      growth and suppresses the numbers of clostridia in the faeces with a trend for
      higher percentage of stool bifidobacteria and lower percentage of E. coli.

PMID- 17433578
TI  - How can we evaluate developmental care practices prior to their implementation in
      a neonatal intensive care unit?
AB  - Developmental care is designed to allow optimal neurobehavioral development of
      the preterm infant. The Neonatal Individualized Developmental Care and Assessment
      Program (NIDCAP) associates various strategies and focuses on individualized,
      family-oriented care. Scientific evaluation of developmental care is needed.
      Randomized controlled trials are the basis for medical evaluation, but present
      some limitations for developmental care studies. Qualitative research and
      benchmarking could be of interest in this field of neonatal medicine.

PMID- 17433580
TI  - SDS-polyacrylamide gel electrophoresis of buffalo bulls seminal plasma proteins
      and their relation with semen freezability.
AB  - The objective of this study was to evaluate the protein profiles of seminal
      plasma in buffalo bulls and to examine their correlation with semen
      characteristics. Semen of 10 buffalo bulls were collected by a bovine artificial
      vagina. Semen characteristics (motility, morphology, viability and concentration)
      were recorded. A part of the semen sample (1 ml) was diluted by tris-egg yolk
      glycerol extender, packed in French straws and was frozen in liquid nitrogen. The
      straws were later thawed and semen characteristics were compared with those of
      the fresh semen. Seminal plasma was harvested by centrifugation; treated with
      cold ethanol and then, underwent SDS-polyacrylamide gel electrophoresis (PAGE).
      Twenty five protein bands were identified on the gel, of which those of <35.5 kDa
      were prominent (72% of the bands). Of these protein fractions, 24.5 kDa was
      significantly correlated with sperm progressive motility in fresh and viability
      in frozen-thawed semen while 45 kDa bands were correlated with abnormal
      morphology in frozen-thawed semen; 55 kDa protein fractions were correlated with
      sperm viability of fresh semen. Progressive motility, viability and abnormal
      sperm morphology of frozen-thawed semen were highly correlated with these
      parameters in the fresh semen. In conclusion, seminal plasma protein fractions in
      buffalo bulls are similar to those reported in other animal species and have some
      correlations with semen characteristics before and after freezing.

PMID- 17433579
TI  - Xanthine oxidoreductase and neurological sequelae of carbon monoxide poisoning.
AB  - Neurological sequelae (NS) is a common complication of carbon monoxide (CO)
      poisoning and structural alterations of myelin basic protein have been proven to
      initiate immunological reactions leading to NS. To determine whether xanthine
      oxidoreductase (XOR) participates in the pathophysiology of CO-mediated NS, we
      examined myelin basic protein in CO poisoned XOR-depleted rats and performed
      radial maze studies to evaluate the alteration of cognitive function. Carbon
      monoxide poisoned XOR-depleted rats did not exhibit myelin basic protein
      alterations or impaired cognitive function, both found in CO poisoned control
      rats. These results indicate that XOR is essential to the pathological cascade of
      CO-mediated NS.

PMID- 17433581
TI  - Pregnancy rates in lactating dairy cattle following supplementation of
      progesterone after artificial insemination.
AB  - Poor conception rates in highly productive lactating cattle is especially
      prevalent in large, intensively-managed commercial herds. One of the causative
      factors is sub-optimal pre-implantation embryonic development which appears to
      result from inadequate circulating concentrations of progesterone. In the present
      study, the efficacy of very modest progesterone supplementation, between Days 3.5
      and 10 post-AI, on pregnancy rates was determined in a commercial herd where
      bovine somatotropin (bST) was used as a management tool. All lactating cattle
      that were deemed to be in estrus and inseminated over a 4-week period were
      randomly assigned to either a control group (no treatment) or CIDR-1.9g
      (previously used for estrous synchronization) treatment from Day 3.5 to Day 10
      post-AI. Milk samples were collected four times: on the day of AI, at Day 2 or 3,
      at Day 4 and at Day 22 post-AI and were analyzed for progesterone content. Data
      from a total of 130 breedings were used in the final analysis. The CIDR treatment
      increased circulating concentrations of progesterone in treated animals over
      those of control animals on Day 4 by 0.7ng/ml (P<0.05) and increased pregnancy
      rate from 35% (22/63) to 48% (32/67) (P=0.068). The effect of treatment was
      greater in first and second lactation cows, where pregnancy rates were 33%
      (18/55) in controls and 51% (31/61) in treated animals (P=0.03). The results of
      this study indicate that the timing of onset of the progesterone influence is
      important for successful pregnancy outcome, particularly in first and second
      lactation cows.

PMID- 17433582
TI  - Seminal plasma non-heparin binding proteins (NHBP) reduce the cryoinjury to
      buffalo cauda epididymal spermatozoa induced by heparin binding proteins (HBP).
AB  - Previous cryopreservation studies with buffalo cauda epididymal spermatozoa have
      reported a deleterious effect of seminal plasma heparin binding protein (HBP).
      The amount of HBP used in these studies was meager compared to the normal level
      of HBP in the buffalo ejaculate, still the damage induced upon the spermatozoa
      was substantial when compared to that incurred to the spermatozoa during routine
      freezing of ejaculated semen. Thus there might be some factor(s) in the seminal
      plasma, which reduce the deleterious effect of HBP on spermatozoa during
      cryopreservation of ejaculated semen. This study was conducted to investigate for
      the presence of any such factor in buffalo seminal plasma. Seminal plasma
      proteins were separated on their heparin binding properties as heparin binding
      (HBP) and non-heparin binding (NHBP). The separated proteins were added to the
      extender of buffalo cauda epididymal semen for cryopreservation either alone or
      in combination. The spermatozoa were assessed for progressive motility,
      viability, acrosomal integrity and response to hypo-osmotic solution test (HOST)
      at prefreeze and post-thaw stages of cryopreservation. NHBP was found to provide
      some degree of protection to buffalo spermatozoa against cryopreservation stress
      as well as the deleterious effect of HBP during cryopreservation.

PMID- 17433583
TI  - Differential expression of lipopolysaccharide-induced TNF-alpha factor (LITAF) in
      reproductive tissues during induced molting of white leghorn hens.
AB  - The reproductive remodeling during molting appears to be a complex physiological
      mechanism regulated by multiple host factors. Lipopolysaccharide (LPS) induced
      TNF-alpha factor (LITAF) is one of the transcription factors controlling the
      expression of TNF-alpha and other cytokines. In the present investigation, we
      studied the involvement of LITAF in the regression of reproductive tissues of
      molting birds. Semi-quantitative RT-PCR analysis revealed that LITAF mRNA was
      generally expressed in both ovary and oviduct. In the molting birds, i.e. those
      subjected to feed withdrawal (FW) or fed high levels of zinc (ZnF) birds, the
      LITAF expression was upregulated significantly in the ovary after 4 days of
      molting (DOM). However, LITAF mRNA levels were three-fold higher in ZnF birds,
      which might be responsible for a greater degree of follicular atresia. In the
      oviduct of FW birds, peak LITAF expression was noticed on 4DOM and the levels
      remained significantly higher until the end of the experiment. In ZnF birds,
      LITAF expression reached its peak on 1DOM and subsequently downregulated to basal
      levels on 2DOM. This indicated that constantly higher LITAF expression might be
      required for complete regression of the oviduct during molting. In conclusion,
      LITAF might be one of the major transcription factors controlling reproductive
      regression in chicken, as the expression levels were associated with the
      regression pattern.

PMID- 17433585
TI  - Statistical cluster analysis of pharmaceutical solvents.
AB  - High efficiency in polymorph screening and crystallization optimization can be
      gained by judicious selection of solvents for the study design. Examination of
      all 57 (classes 2 and 3) pharmaceutical solvents may enable a complete study
      design but is costly in terms of time and resources. Based on a 17 descriptor
      dataset specifically constructed for all the classes 2 and 3 pharmaceutical
      solvents recognized by the International Conference of Harmonization (ICH), an
      optimal two-stage cluster analysis was carried out together with principal
      component analysis as a dimensionality and colinearity reduction pre-processor.
      Both hierarchical average linkage cluster analysis and non-hierarchical K-means
      cluster analysis converged on a 20-cluster solution with strong statistical
      criteria support and excellent agreement in cluster memberships, which can be
      reasonably interpreted from a chemical perspective. This 20-cluster solution is
      offered as an option for design of more efficient solid state screening studies.
      Rather than designing a polymorph screen to include all 57 solvents, the
      inclusion of a single member from each of the 20 clusters would be expected to
      adequately represent the full range of solvent properties exhibited by the entire
      57 member solvent set.

PMID- 17433584
TI  - Bioerodible devices for intermittent release of simvastatin acid.
AB  - The association polymer system of cellulose acetate phthalate (CAP) and Pluronic
      F-127 (PF-127) was used to create intermittent release devices for mimicking the
      daily injection of simvastatin that has been reported to stimulate bone
      formation. To enhance solubility in water, prodrug simvastatin was modified by
      lactone ring opening, which converts the molecule to its hydroxyacid form. CAP/PF
      127 microspheres incorporating simvastatin acid were prepared by a water-acetone
      oil-water (W/A/O/W) triple emulsion process. Devices were then fabricated by
      pressure-sintering UV-treated blank and drug-loaded microspheres. Using a
      multilayered fabrication approach, pulsatile release profiles were obtained.
      Delivery was varied by changing loading, number of layers, blend ratio, and
      incubation conditions. To determine the cellular effects of intermittent exposure
      to simvastatin acid, MC3T3-E1 cells were cultured with either alternating or
      sustained concentrations of simvastatin acid in the medium, and DNA content,
      alkaline phosphatase activity, and osteocalcin secretion were measured. For all
      three cell responses, cultures exposed to simvastatin acid showed higher activity
      than did control cultures. Furthermore, cell activity was greater for cells
      cultured with intermittent concentrations of simvastatin acid compared to cells
      that were constantly treated. These results imply that devices intermittently
      releasing simvastatin acid warrant further study for locally promoting
      osteogenesis.

PMID- 17433586
TI  - Changes in P2Y4 receptor expression in rat cochlear outer sulcus cells during
      development.
AB  - Extracellular adenosine triphosphate (ATP) released from cellular sources plays
      an important role in variety of the cochlear physiologic processes. The primary
      purinergic receptor subtype in the cochlea is the P2X2 receptor, which is a
      subtype of P2X receptor. This receptor appears to mediate a protective decrease
      in the electrical driving force in response to acoustic overstimulation. Outer
      sulcus cells (OSCs) in the cochlear lateral wall appear to maintain an adequate
      K+ concentration in the cochlear endolymph in response to varying intensities of
      auditory stimulation. However, little is known about developing OSCs. The purpose
      of this study was to investigate subtypes of purinergic receptors in developing
      rat OSCs using a voltage-sensitive vibrating probe. Results showed that only two
      P2 receptors (P2Y4 and P2X2) contributed to the regulation of short circuit
      currents in neonatal OSCs. ATP increased cation absorption via apical
      nonselective cation channels after activating P2Y4 receptors in early neonatal
      OSCs. P2Y4 expression rapidly declined postnatally and reached near adult levels
      on postnatal day 14. P2X2 was co-expressed with P2Y4 in early neonatal OSCs.
      Temporal changes in P2Y4 during OSC development might be involved in the
      establishment of the endolymphatic ion composition needed for normal auditory
      transduction and/or specific cellular differentiation.

PMID- 17433587
TI  - The MeOH extract of Pleurospermum kamtschaticum and its active component
      buddlejasaponin (IV) inhibits intrinsic and extrinsic hyperlipidemia and
      hypercholesterolemia in the rat.
AB  - The inhibitory effect of the MeOH extract of Pleurospermum kamtschaticum
      (Umbelliferase) and its fractions were tested in hyperlipidemic and
      hypercholesterolemic rats using four animal models induced using poloxamer-407 or
      using Triton WR-1339 as intrinsic inducers and by 30% corn oil or high
      cholesterol diet as extrinsic inducers. We measured serum triglyceride, total
      cholesterol, HDL-cholesterol and LDL-cholesterol levels as measures of its
      hypocholesterolemic or hypolipidemic effects. Since the MeOH extract and the BuOH
      fraction of Pleurospermum kamtschaticum were found to be active using these four
      hypolipidemic assays, its major saponin buddlejasaponin IV {BS(IV)} isolated from
      the BuOH fraction were also tested to demonstrate the active components. BS(IV)
      was found to significantly inhibit hypercholesterolemia and hyperlipidemia by
      extrinsic and intrinsic inducers. In particular, BS(IV) reduced the blood
      thiobarbituric acid reactive substance (TBARS) and hydroxy radical levels, and
      increased superoxide dismutase activity in high cholesterol diet-induced rats,
      thus suggesting that BS(IV) reduces oxidative stress caused by a high cholesterol
      diet. Moreover, these effects of BS(IV) were comparable to probucol, which was
      used as a positive control. These results suggested that Pleurospermum
      kamtschaticum which is traditionally used to treat atherosclerosis and its active
      major saponin BS(IV) could be used to treat hypercholesterolemia or
      hyperlipidemia.

PMID- 17433588
TI  - Influence of Sutherlandia frutescens extracts on cell numbers, morphology and
      gene expression in MCF-7 cells.
AB  - Sutherlandia frutescens is a well-known South African herbal remedy traditionally
      used for stomach problems, internal cancers, diabetes, various inflammatory
      conditions and recently to improve the overall health in cancer and HIV/AIDS
      patients. The influence of crude Sutherlandia frutescens extracts (prepared with
      70% ethanol) was investigated on cell numbers, morphology, and gene expression
      profiles in a MCF-7 human breast adenocarcinoma cell line. Time-dependent (24,
      34, 48 and 72 h) and dose-dependent (0.5-2.5 mg/ml) studies were conducted
      utilizing spectrophotometrical analysis with crystal violet as DNA stain. A
      statistically significant decrease to 50% of malignant cell numbers was observed
      after 24 h of exposure to 1.5 mg/ml Sutherlandia frutescens extract when compared
      to vehicle-treated controls. Morphological characteristics of apoptosis including
      cytoplasmic shrinking, membrane blebbing and apoptotic bodies were observed after
      24h of exposure. A preliminary global gene expression profile was obtained by
      means of microarray analysis and revealed valuable information about the
      molecular mechanisms and signal transduction associated with 70% ethanolic
      Sutherlandia frutescens extracts.

PMID- 17433589
TI  - Antidiarrhoeal and antimicrobial activities of Emilia coccinea (Sims) G. Don
      extracts.
AB  - Emilia coccinea (Sims) G. Don is reported to possess a number of medicinal
      properties including antidiarrhoeal and antimicrobial activities. The
      antidiarrhoeal effects of both methanol and aqueous extracts of the leaves of
      Emilia coccinea were studied in rats against castor oil-induced diarrhoea at the
      doses of 200, 400 and 600 mg/kg body weight. The methanol extract, and to a
      lesser extent the aqueous extract, significantly prolonged the time for
      diarrhoeal induction; it reduced the frequency of diarrhoea episodes and
      decreased the propulsion of charcoal meal through the gastrointestinal tract in a
      dose dependent manner. The aqueous extract did not have any antimicrobial
      activity at the tested concentration (5 mg/ml), but the methanol extract was most
      active on Escherichia coli. These results may support the fact that this plant is
      used traditionally to cure diarrhoea.

PMID- 17433590
TI  - Genetic population data of 12 STR loci of the PowerPlex Y system in the state of
      Sao Paulo population (Southeast of Brazil).
AB  - Allele frequency distributions and population data for 12 Y-chromosomal short
      tandem repeats (STRs) included in the PowerPlex Y Systems (Promega) were obtained
      for a sample of 200 healthy unrelated males living in Sao Paulo State (Southeast
      of Brazil). A total of 192 haplotypes were identified, of which 184 were unique
      and 8 were found in 2 individuals. The average gene diversity of the 12 Y-STR was
      0.6746 and the haplotype diversity was 0.9996. Pairwise analysis confirmed that
      our population is more similar with the Italy, North Portugal and Spain, being
      more distant of the Japan.

PMID- 17433592
TI  - Acute stridor caused by a previously asymptomatic large oropharyngeal spindle
      cell lipoma.
AB  - Lipomas of the larynx, oropharynx and hypopharynx are rare, accounting for
      approximately 1% of benign laryngeal neoplasms. Spindle cell lipoma is a rarer
      histological variant characterised by mature adipocytes mixed with collagen
      forming spindle cells. We present an unusual case of a 62-year-old lady who
      acutely presented to the emergency department with a large spindle cell lipoma
      arising from the vallecula. This lipoma was causing intermittent stridor unless
      traction was applied to it. Despite the size of the lesion, she had been
      completely asymptomatic prior to this single episode. To our knowledge, only one
      previous case of a spindle cell lipoma has been reported as specifically arising
      from the vallecula. This case also appears to be the largest reported from the
      oropharynx (17 cm length, 4 cm width). The tumour was completely removed
      endoscopically and the patient made an excellent recovery, returning home 3 days
      post-operatively. The histology, management and follow up of these lipomas are
      discussed.

PMID- 17433591
TI  - Submucous turbinectomy combined with posterior nasal neurectomy in the management
      of severe allergic rhinitis: clinical outcomes and local cytokine changes.
AB  - OBJECTIVES: Submucous resection of the inferior turbinate is one of the
      recommended methods to alleviate nasal symptoms in patients with severe allergic
      rhinitis patients in terms of postoperative results and preservation of nasal
      function. Posterior nasal neurectomy, recently developed by Kikawada, is a novel
      method to selectively cut the neural bundles out from the sphenopalatine foramen
      and to diminish the complaints of hypersecretion. This study was carried to
      examine the clinical effectiveness and changes in local cytokine levels of this
      combined surgical procedure. METHODS: Twenty-three patients with severe perennial
      allergic rhinitis underwent submucous turbinectomy combined with posterior nasal
      neurectomy under general anesthesia. The patients' subjective nasal symptoms were
      examined at each visit. The levels of interleukin-5 (IL-5), eotaxin and regulated
      on activation, normal T cell expressed and secreted (RANTES) in nasal lavages
      were measured before and 6 month after surgery. Nasal mucosa of the inferior
      turbinate was also obtained for histopathological examination in some cases.
      RESULTS: The mean symptom scores for sneeze, rhinorrhea, nasal obstruction, and
      total severity were all statistically decreased after surgery. Therapeutic
      effects continued to be apparent as long as 3 years after surgery. The mean
      levels of both IL-5 and eotaxin significantly decreased after surgery, but that
      of RANTES remained unchanged. Histopathological examination revealed that the
      number of inflammatory cells and nasal glands markedly reduced in lamina propria
      and the epithelial layer became covered with stratified columnar cells.
      CONCLUSION: Submucosal turbinectomy with posterior nasal neurectomy has
      remarkably improved subjective nasal symptoms in patients with severe allergic
      rhinitis on a long-term follow-up basis. The present study also demonstrates that
      the clinical effectiveness of the procedure is accompanied by decreases in local
      inflammatory cell infiltration and the related cytokine production.

PMID- 17433593
TI  - [EPH, 2007, and all "online"].

PMID- 17433594
TI  - Endocrine tumor abdomen.

PMID- 17433595
TI  - Interobserver-variability of lung nodule volumetry considering different
      segmentation algorithms and observer training levels.
AB  - OBJECTIVE: The aim of this study was to investigate the interobserver variability
      of CT based diameter and volumetric measurements of artificial pulmonary nodules.
      A special interest was the consideration of different measurement methods,
      observer experience and training levels. MATERIALS AND METHODS: For this purpose
      46 artificial small solid nodules were examined in a dedicated ex-vivo chest
      phantom with multislice-spiral CT (20 mAs, 120 kV, collimation 16 mm x 0.75 mm,
      table feed 15 mm, reconstructed slice thickness 1mm, reconstruction increment 0.7
      mm, intermediate reconstruction kernel). Two observer groups of different
      radiologic experience (0 and more than 5 years of training, 3 observers each)
      analysed all lesions with digital callipers and 2 volumetry software packages
      (click-point depending and robust volumetry) in a semi-automatic and manually
      corrected mode. For data analysis the variation coefficient (VC) was calculated
      in per cent for each group and a Wilcoxon test was used for analytic statistics.
      RESULTS: Click-point robust volumetry showed with a VC of <0.01% in both groups
      the smallest interobserver variability. Between experienced and un-experienced
      observers interobserver variability was significantly different for diameter
      measurements (p=0.023) but not for semi-automatic and manual corrected volumetry.
      A significant training effect was revealed for diameter measurements (p=0.003)
      and semi-automatic measurements of click-point depending volumetry (p=0.007) in
      the un-experienced observer group. CONCLUSIONS: Compared to diameter measurements
      volumetry achieves a significantly smaller interobserver variance and advanced
      volumetry algorithms are independent of observer experience.

PMID- 17433596
TI  - Centrifugal (inside-out) enhancement of liver hemangiomas: a possible atypical
      appearance on contrast-enhanced US.
AB  - OBJECTIVE: To report the prevalence and to describe the atypical centrifugal
      (inside-out) appearance of contrast-enhancement of liver hemangiomas on contrast
      enhanced sonography. MATERIALS AND METHODS: Baseline and SonoVue-enhanced
      ultrasonography of 92 patients with 158 liver hemangiomas - considered atypical
      at grey-scale examination and confirmed by computed tomography, magnetic
      resonance imaging and ultrasound follow-up - were reviewed in consensus by two
      experienced radiologists, who evaluated baseline echogenicity and the dynamic
      enhancement pattern of each lesion looking for the presence of central enhancing
      foci in the arterial phase followed by a centrifugal (inside-out) enhancement in
      the portal-venous and late phases. RESULTS: After administration of SonoVue,
      12/158 hemangiomas (7.6%) (size range: 1-7cm; mean: 3.2cm) in seven patients (5
      women, 2 men; age range: 34-71 years, mean: 50.8 years) showed a central
      enhancing focus in the arterial phase followed by a centrifugal enhancement in
      the portal-venous and late phases. In all cases centrifugal enhancement was
      incomplete at contrast-enhanced sonography, whereas computed tomography and/or
      magnetic resonance imaging were able to depict a complete and homogeneous fill
      in. CONCLUSION: Radiologist should be aware that centrifugal (inside-out)
      appearance on contrast-enhanced sonography is a rare but possible feature of
      liver hemangioma.

PMID- 17433597
TI  - Ultrasonography, computed tomography and magnetic resonance imaging for diagnosis
      of ovarian carcinoma.
AB  - Our objective was to compare US, CT, and MR imaging in differentiation of
      malignant from benign ovarian tumors. Through an electronic literature search and
      manual review of bibliographies (January 1990 to June 2006), relevant studies on
      the diagnostic performance of US, CT, and MR imaging in the differentiation
      between benign and malignant ovarian tumours were identified. Sixty-nine articles
      were included, yielding 143 studies. Data on the accuracy of the different
      imaging modalities were analyzed and compared by constructing summary receiver
      operating characteristic (ROC) curves. Our results suggest that US techniques
      seems to be similar with CT and MRI in differentiation of malignant from benign
      ovarian tumors. The results also revealed that color Doppler flow imaging alone
      is significantly inferior to combined US techniques, morphologic assessment alone
      and contrast enhanced US in diagnosis of ovarian cancer. In conclusion, US
      morphologic assessment still is the most important and common modality in detect
      ovarian cancer.

PMID- 17433598
TI  - CT and MR imaging findings of endocrine tumor of the pancreas according to WHO
      classification.
AB  - The pancreatic endocrine tumors are rare neuroendocrine tumors of the pancreas
      originating from totipotential stem cells or differentiated mature endocrine
      cells within the exocrine gland. Endocrine tumors are usually classified into
      functioning and non-functioning tumors and presents with a range of benignity or
      malignancy. In this article, we present the various CT and MR imaging findings of
      endocrine tumors of pancreas according to recent WHO classification.

PMID- 17433599
TI  - Chromatography-mass spectrometry methods for the quantitation of statins in
      biological samples.
AB  - The 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase inhibitors, more
      commonly known as 'statins', are a novel class of drugs widely used for the
      treatment of hypercholesterolaemia in patients with established cardiovascular
      disease as well as those at high risk of developing atherosclerosis. Published
      chromatographic-mass spectrometric methods for the quantification of presently
      available seven statins, atorvastatin, simvastatin, lovastatin, pravastatin,
      fluvastatin, rosuvastatin and pitavastatin are reviewed. High performance liquid
      chromatography (HPLC) in combination with tandem mass spectrometry (MS/MS) is the
      analytical technique of choice for the quantification of statins in biological
      samples. This review envisages that most of the methods used for quantification
      of statins are in plasma and they are suitable for therapeutic drug monitoring of
      these drugs.

PMID- 17433600
TI  - Structural elucidation of in vivo and in vitro metabolites of anisodine by liquid
      chromatography-tandem mass spectrometry.
AB  - Liquid chromatography-electrospray ionization tandem mass spectrometry (LC
      ESIMSn) was employed to investigate the in vivo and in vitro metabolism of
      anisodine. Feces, urine and plasma samples were collected after ingestion of 20
      mg anisodine to healthy rats. Feces and urine samples were cleaned up by liquid
      liquid extraction and solid-phase extraction procedures (C18 cartridges),
      respectively. Methanol was added to plasma samples to precipitate plasma
      proteins. Anisodine was incubated with homogenized liver and intestinal flora of
      rats in vitro, respectively, followed by extraction with ethyl acetate. LC-MSn
      was used for the separation and identification of the metabolites using C18
      column with mobile phase of methanol/0.01% triethylamine solution (2 mM, adjusted
      to pH 3.5 with formic acid) (60:40, v/v). The results revealed that five
      metabolites (norscopine, scopine, alpha-hydroxytropic acid, noranisodine and
      hydroxyanisodine) and the parent drug existed in feces. Three new metabolites
      (dimethoxyanisodine, tetrahydroxyanisodine and trihydroxy-methoxyanisodine) were
      identified in urine. Four metabolites (norscopine, scopine, hydroxyanisodine and
      anisodine N-oxide) and the parent drug were detected in plasma. Two hydrolyzed
      metabolites (scopine and alpha-hydroxytropic acid) were found in rat intestinal
      flora incubation mixture, and two metabolites (aponoranisodine and anisodine N
      oxide) were identified in homogenized liver incubation mixture.

PMID- 17433601
TI  - System suitability in bioanalytical LC/MS/MS.
AB  - System suitability is widely recognized as a critical component of bioanalysis.
      This paper discusses a generic system suitability test that monitors instrument
      performance throughout a run when used for liquid chromatography tandem mass
      spectrometry (LC/MS/MS) in bioanalysis. This system suitability process is
      designed to ensure that the LC/MS/MS system is performing in a manner that leads
      to the production of accurate and reproducible data that can be submitted with
      confidence to regulatory agencies. This process contains tests for signal
      stability, carryover, and instrument response. This approach is integrated
      throughout an analytical run and has been used in the analysis of over 25,000
      batches of clinical samples. Two case studies are presented in which quality
      control samples and standards meet all acceptance criteria (based on Standard
      Operating Procedures and the Food and Drug Administration's recommendations for
      bioanalytical method validation) but failed the proposed system suitability test,
      and thus were rejected. In these case studies, the concentrations of a
      significant number of clinical samples (over 35%) were affected, resulting in
      changes of more than 15% when the samples were reanalyzed. These data indicate
      that the poor performance of an LC/MS/MS system could adversely affect the
      calculated concentrations of unknown samples even though the results for quality
      control samples appear to be acceptable.

PMID- 17433602
TI  - Patient expectations on lipid-lowering drugs.
AB  - OBJECTIVE: The objective of this study was to assess expectations of effect when
      using statins in a treatment population. Further the aim was to examine factors,
      including history and concurrent risk of coronary heart disease, associated with
      a higher and lower treatment belief. METHODS: Eight hundred and twenty-nine (829)
      Swedish patients using statins completed postal questionnaires about their
      health, life style, cardiovascular risk factors and expectation of the treatment.
      Expected treatment benefit was used as outcome measurement. RESULTS: A medical
      history of coronary heart disease did not affect treatment expectations. Patients
      with a high risk of cardiovascular disease reported a slightly lower expectation
      of the treatment effect at a 10-year perspective (p<0.01) but not at shorter time
      perspectives. Low satisfaction with the explanation of the purpose of the
      treatment and a poor perceived control of own health was associated with a more
      negative view on treatment benefit. CONCLUSION: The rationale applied by
      physicians prescribing statins does not seem to relate to the patients'
      expectations, whereas factors relating to the patient-physician relationship, the
      social situation and the perceived control of health seem to affect patient
      belief. PRACTICE IMPLICATIONS: The association between patients' poor
      satisfaction of treatment explanation and a low belief in treatment benefits
      emphasizes the importance of the patient-physician communication. It is suggested
      that clinical tools are developed in order to identify patients with poor belief
      in treatment benefit since tailored education for this group might reduce the
      risk of non-compliance and subsequently reduce the risk of coronary heart
      disease.

PMID- 17433603
TI  - Shared decision making: the reliability of the OPTION scale in Italy.
AB  - OBJECTIVE: To provide psychometric characteristics of the Italian language
      version of the OPTION scale and descriptive statistics on patients' involvement.
      The OPTION scale assesses the extent to which clinicians involve patients in
      therapeutic decisions. The English language version has a Cohen's kappa score for
      individual items ranging from 0.45 to 0.98 and an intraclass correlation
      coefficient (ICC) for the total score of 0.77. METHODS: Six male GPs provided 235
      audiotaped consultations with consecutive patients who had attended for a new
      illness episode over a 2-month period. Thirty interviews were rated by two raters
      to assess inter- and intra rater as well as test-retest reliability of the
      Italian language version of the OPTION scale. Based on the whole sample,
      Cronbach's alpha and an exploratory factor analysis were performed to assess
      internal validity and to determine factor loadings. RESULTS: Cohen's kappa values
      were comprised between 0.29 and 0.73, the ICC at test and retest was 0.85 and
      0.81 and Cronbach's alpha 0.82. The ratings for each OPTION item showed a skewed
      distribution: the majority of scores (>70%) were between 0 (behaviour absent) and
      2 (minimum skill level). CONCLUSION: The reliability indices were satisfactory
      and similar to those reported for the original OPTION. PRACTICE IMPLICATIONS:
      OPTION can be used for both teaching purposes and research, as well as for future
      cross-national comparisons.

PMID- 17433604
TI  - Technical limitations of lymph node mapping in pancreatic cancer.
AB  - AIM: The high incidence of lymphatic and peri-neural invasion in pancreatic
      cancer results in poor loco-regional control. Radical pancreatico-duodenectomy
      may achieve better loco-regional control, but is accompanied by increasing
      morbidity. Our hypothesis was that if intra-operative mapping of pathological
      lymph nodes (LN) is technically feasible in pancreatic cancer, it would allow for
      selective radical resection. METHODS: In an ethically approved and statistically
      powered feasibility study of 72 (stopped after 20% enrollment) patients with
      suspected pancreatic cancer undergoing resection, we injected methylene blue dye
      peri- and intra-tumorally and studied its progress to identify putative 'sentinel
      lymph node(s)'. The Kausch-Whipple procedure (or total pancreatectomy, if
      required) was carried out in addition to radical LN dissection, which was
      evaluated histopathologically according to the Japanese criteria. RESULTS: Over
      18 months, 14/16 patients prospectively recruited underwent lymph node mapping
      and a mean of 20 (range 11-37) LNs per patient were harvested. Methylene blue dye
      injection identified blue LN(s) in 4/14 patients, none of which were positive for
      malignant deposits, whilst 10/14 patients had LN metastases. The commonest
      stations for LN metastasis were 17A or B (9/10), 8A (2/10) and 6 (3/10). The
      median survival for the 13 patients with cancer was 22.3 months (IQR: 10.4-30
      months). CONCLUSION: Sentinel lymph node mapping is not technically feasible in
      pancreatic cancer.

PMID- 17433605
TI  - Single nucleotide polymorphism in the promoter region of human alpha-fetoprotein
      (AFP) gene and its significance in hepatocellular carcinoma (HCC).
AB  - BACKGROUND: Variations of serum AFP levels in HCC patients and cell lines are
      likely due to the differential activity of enhancer/silencer elements that
      control AFP. To understand the potential mechanism underlying the differential
      expression of AFP, we have examined the sequence of the AFP promoter in HCC.
      METHODS: Direct DNA sequencing was carried out to sequence 980 bp of AFP promoter
      of DNA samples isolated from 83 HCC patients. RESULTS: Three novel SNPs in the
      promoter region of the AFP gene, which have not been previously reported, were
      found at positions -330, -401 and -692. The level of serum AFP was significantly
      higher in HCC patients with the CT genotype of 330 SNP or the AG genotype of the
      401 SNP. The genotype of CG in 692 SNP was also associated with a significant
      elevated level of serum AFP, and further this genotype appeared to be associated
      with the high risk of HCC development. 401 SNP and 692 SNP were located at the
      positions of known binding sites for transcription factors that have a role in
      the production of AFP and the growth of tumors. CONCLUSIONS: The novel
      polymorphisms identified in the promoter region of the AFP gene may be
      pathologically significant in HCC.

PMID- 17433606
TI  - Evaluation of the surgical completeness after total thyroidectomy for
      differentiated thyroid carcinoma.
AB  - BACKGROUND: To quantify the rate of patients without thyroid remnants, to
      identify predictive factors for the absence of residual thyroid tissue and to
      evaluate number, site, size and function of thyroid remnants after total
      thyroidectomy for differentiated thyroid carcinoma (DTC). METHODS: Thousand one
      hundred and seventy-eight patients who underwent total thyroidectomy for DTC were
      evaluated; 343 patients with lymph node or distant metastases and 115 patients
      with detectable thyroglobulin autoantibodies (TgAb) were excluded. (131)I
      ablative treatment (RAI) without preliminary diagnostic (131)I whole body scans
      (DxWBS), and 24-h (131)I quantitative neck uptake (RAIU test) and thyroglobulin
      (Tg) off L-T4 evaluation were performed in the remaining 720 pts. In 252 patients
      a 99mTc-pertechnetate pre-operative thyroid scan (99mTc-scan) was used for
      comparison with (131)I neck scans after RAI to evaluate site of thyroid remnants.
      Only patients with thyroid remnants were evaluated for successful ablation 6-10
      months after RAI. RESULTS: Post-treatment whole body scan (TxWBS) demonstrated
      lack of thyroid remnants in 50/720 patients and the best predictive factors for
      the absence of residual thyroid tissue were RAIU <1% and undetectable Tg off L
      T4. Thyroid remnants were present in 670/720 patients. In 252 patients with
      (99m)Tc-scan, 617 sites of functioning thyroid tissue were found: 381 within and
      236 outside the thyroid bed. Complete successful ablation was achieved in 610/670
      patients with thyroid remnants. CONCLUSIONS: This study confirms that most
      patients (93.1%) have thyroid remnant after total thyroidectomy for DTC. Most
      thyroid remnants were contralateral to tumour site and were even observed outside
      thyroid bed. However, a real total thyroidectomy, demonstrated by negative TxWBS,
      RAIU <1% and undetectable Tg off L-T4, was achieved in 6.9% of patients.

PMID- 17433607
TI  - Macroscopic classification of superficial neoplastic lesions of the oral mucosa:
      a preliminary study.
AB  - BACKGROUND: Careful endoscopic classification of macroscopic appearance of
      superficial neoplasias of the gastrointestinal tract is essential in the early
      detection and appropriate treatment of cancer. It has contributed to introduce
      minimally invasive endoscopic surgery and has significantly improved survival of
      patients with colon and gastric cancers. Squamous cell carcinoma of the oral
      cavity has been characterized, in past and present times, by poor prognosis and
      lack of progress in treatment outcome. Failure in diagnosing oral malignancy at
      an early stage is a major culprit, and the lack of a worldwide adopted
      classification of its macroscopic appearance, similar to that of gastrointestinal
      neoplasias, may have contributed to it. AIM: To test the hypothesis that is
      possible to extend the diagnostic benefit of a classification based upon the
      macroscopic appearance of superficial tumours of the digestive tract to
      superficial carcinoma of the oral mucosa. METHODS: We retrospectively examined a
      group of patients who developed multiple intraepithelial and early invasive
      malignant oral neoplasias, applying a modified version of the Paris
      classification of superficial GI neoplastic lesions. RESULTS: One hundred and ten
      out of 116 (94.9%) of the study lesions had morphological features that accorded
      with the prepared classification. CONCLUSIONS: These preliminary data suggest
      that most superficial early neoplastic lesions of the oral cavity can be easily
      detected using a well-defined classification system similar to that employed in
      the diagnosis of early gastrointestinal malignancy.

PMID- 17433608
TI  - Clinical and imaging experience with yttrium-90 microspheres in the management of
      unresectable liver tumours.
AB  - INTRODUCTION: Selective internal radiation therapy (SIRT) is emerging as a new
      therapeutic modality in recent years for management of non-resectable hepatic
      malignancies. Our experience in clinical application of this treatment is
      reported here. MATERIAL AND METHODS: From June 2004, patients whose liver tumours
      were no longer amenable for any conventional treatment with either chemotherapy
      or surgery were considered for yttrium-90 microspheres treatment after discussion
      at our multidisciplinary meeting. A pre-treatment planning was carried out with
      visceral angiography and technetium-99m macroaggregated albumin (MAA) for
      assessment of both tumour volume and extrahepatic shunting in addition to a
      baseline PET and CT scans, respectively. Two weeks later, a second visceral
      angiogram was performed to deliver the calculated dosage of microspheres into the
      arterial system supplying the tumour. Patients were then followed up with tumour
      markers, repeat PET and CT scans of abdomen at 6 weeks and 3 monthly thereafter.
      RESULT: Twenty-one patients (F=11, M=10; age range 40-75 years, mean=58 years)
      received yttrium-90 microspheres consisting of liver metastases from colorectal
      primary (n=10) and non-colorectal primaries (n=8), and primary liver tumours
      (n=3). One patient received 2 treatments. The mean administered activity of
      microspheres delivered was 1.9 GBq (range 1.2-2.5 GBq). Injection of microspheres
      had no immediate effect on either clinical haematology or liver function tests.
      At follow-up, 86% of patients showed decreased activity on PET scan at 6 weeks
      (p=0.01). The mean pre-treatment SUV was 12.2+/-3.7 and the mean post-treatment
      SUV was 9.3+/-3.7, indicating a significant improvement measured with PET
      activity. Only 13% showed a reduction in the size of tumour on CT scan. For
      patients with colorectal liver metastases, there was no significant reduction in
      CEA level (127+/-115 vs 75+/-72 micro/l, p=0.39). Complications were seen in 4
      patients (19%) including radiation hepatitis (n=2), cholecystitis (n=1) and
      duodenal ulceration (n=1). All resolved without surgical intervention. Seven
      patients died at follow-up from progressive extrahepatic disease (33%).
      CONCLUSION: SIRT should be considered for patients with advanced liver cancer. It
      has a significant effect on liver disease in the absence of extrahepatic disease.
      PET imaging has an integral role in the assessment of patients treated with
      yttrium-90 SIR-Spheres.

PMID- 17433609
TI  - [Cotrimoxazole Pneumocystis jiroveci pneumonia treatment failure: co-infection
      cytomegalovirus role?].
AB  - Pneumocystis jiroveci pneumonia is a classic opportunist infection affecting AIDS
      patients. However it is less frequent since systematic prophylaxis and
      antiretroviral therapies. Treatment resistance is rare in France. We report the
      case of a severe Pneumocystis jiroveci pneumonia with treatment resistance to
      standard treatment and fatal outcome. The different causes of treatment
      resistance, notably the role of CMV co-infection, were reviewed and discussed.

PMID- 17433610
TI  - Inhibition of phosphatidylinositol 3-kinase causes cell death in rat osteoblasts
      through inactivation of Akt.
AB  - Previous evidences indicated that phosphatidylinositol 3-kinase (PI3-kinase) is
      an important regulatory molecule that is involved in the cell growth and
      survival, and inhibition of the PI3-kinase activity enhances apoptotic cell
      death. However, the relationship between PI3-kinase activity and osteoblasts,
      capable of new bone formation, remained unknown. In the present study,
      pharmacological inhibitor of PI3-kinase LY294002 was used to observe the role of
      the PI3-kinase in the growth of rat osteoblasts. To identify its molecular
      mechanism, Western blots analysis and immunocytochemistry were applied to examine
      changes of Akt phosphorylation and its distribution. Our data showed that
      inhibition of PI3-kinase activity significantly triggered the decrease of cell
      growth, cell apoptosis and loss of mitochondrial membrane potential
      (Deltapsi(m)). Osteoblastic dysfunction stimulated by LY294002 was accompanied by
      inactivation of Akt and its redistribution. In all these results demonstrated
      that inhibition of PI3-kinase induced apoptotic cell death, which was mediated by
      inactivation of Akt pathway in rat osteoblasts.

PMID- 17433611
TI  - [Current pathophysiologic approaches to heart failure].
AB  - Heart failure is the consequence of cardiac remodeling that affects all the
      structural and functional aspects of the heart, from its ventricular geometry to
      the molecular components of myocytes and other myocardial cells. This remodeling
      is activated by biomechanical stress from the onset of the causal disease (sudden
      in cases of myocardial infarction and more progressively in cases of
      hypertension, for example). This biomechanical stress combines, depending on the
      cause, diverse degrees of diastolic stretching and systolic overload of the
      ventricles with systemic and tissular neurohormonal modifications. These
      mechanical and neurohormonal factors activate numerous intracellular signaling
      pathways, interconnected in a complex web, and lead to reprogramming the genome
      of the myocytes and other myocardial cells. Activation of some of these pathways
      leads to a beneficial adaptive remodeling (growth, cardiac hypertrophy of
      pregnancy and of athletes) or on the contrary to harmful remodeling (heart
      disease). The predominance of the stimulation of the harmful pathways over that
      of the beneficial pathways in heart disease is responsible for progression
      towards heart failure. Current research aims at identifying new pathways and
      participants in the beneficial and harmful remodeling of the myocardium in order
      to develop new drugs that will block ever more specifically the harmful pathways
      but also stimulate the beneficial ones, to prevent progression towards heart
      failure.

PMID- 17433612
TI  - [Unhealthy homes: possible interventions and their efficacy].
AB  - Numerous health risks have been identified in dwellings and are a public health
      priority. Homes most often accumulate several different risks. Intervention
      programs must take this reality into account. Identification of a source of
      chemical pollution in the home makes it possible to correct indoor air quality
      quickly and inexpensively and provides immediate health benefits. Extermination
      of mites requires implementation of a group of complementary techniques in all
      contaminated areas, with help, when possible, from an indoor environment
      counselor. A team of multidisciplinary indoor habitat and health advisors must
      assess the health risks of the home. This inexpensive strategy reduces risks,
      although its effectiveness still requires confirmation. When the building has
      structural defects or abnormalities, more complex methods of renovation, or even
      moving, are necessary. There again, a complete assessment of their benefits to
      occupants' health is necessary.

PMID- 17433613
TI  - The cognitive disorders examination (Codex) is a reliable 3-minute test for
      detection of dementia in the elderly (validation study on 323 subjects).
AB  - BACKGROUND: Dementia often remains undiagnosed until it has reached moderate or
      severe stages, thereby preventing patients and their families from obtaining
      optimal care. Tools that are easy to use in primary care might facilitate earlier
      detection of dementia. AIM: Develop and validate a very brief test for the
      detection of dementia. METHODS: In the derivation study, we recorded educational
      level, Mini Mental State Examination (MMSE) scores and subscores and results of a
      simplified clock-drawing test (sCDT) for consecutive patients attending a single
      memory clinic over a two-year period,. Dementia was diagnosed according to DSM-IV
      criteria. The independent variables related to dementia were determined by a
      multivariable logistic model (MLM) and used to develop a decision tree to predict
      this diagnosis. In the validation study, the decision tree was applied to
      consecutive patients of six memory clinics for whom status about dementia was
      previously determined with DSM-IV criteria. The decision tree, MLM, and MMSE were
      applied to detect dementia in these patients. The sensitivity and specificity of
      each diagnostic tool were estimated and compared. RESULT: Of 242 patients in the
      derivation study, the following independent variables were correlated with
      dementia: sex, sCDT, and two MMSE subscores - the 3-word recall test and spatial
      orientation. We used Bayesian statistics to develop a brief 2-step decision
      analysis tree (2-3 min.), which we named Codex (cognitive disorders examination).
      The validation study applied Codex to 323 patients. Sensitivity was 93% and
      specificity 85%. The corresponding values were 88% and 87% for the MLM, 94% and
      67% or 91% and 70% for the MMSE, depending on the MMSE cutoff score. The
      sensitivity of Codex was significantly higher than that of MLM, and its
      specificity was significantly greater than that of MMSE. CONCLUSION: Codex is a
      simple, brief, and reliable test for detecting dementia and requires three
      minutes or less to administer. Its simplicity and brevity make it appropriate for
      and easy to use in primary care.

PMID- 17433614
TI  - [Education and multidisciplinary management in chronic heart failure].
AB  - Heart failure is a common, serious and expensive disease. It causes repeated
      hospitalizations, decreases patients' quality of life, and reduces the
      independence of elderly patients. It constitutes a major public health problem
      for which a new organization of care appears necessary. The components of this
      management, which requires a multidisciplinary organization, are a major
      involvement by paramedical personnel, coordination of care, and patient
      education. Patient education is a continuous patient-centered process directed at
      helping them become competent in reconciling the difficulties associated with the
      disease, treatment requirements and quality of life. Their own security requires
      that they learn to identify and cope with signs of disease aggravation. The other
      educational objectives are negotiated with the patient and are therefore
      individualized. The general practitioner plays an essential role in patients'
      medical management but also in their education, starting the program and
      providing additional information; consistency with the educational team is
      essential.

PMID- 17433615
TI  - [Improving perioperative management of oral anticoagulants in 2007].
AB  - Preoperative interruption of oral anticoagulants is not essential for every
      procedure performed during surgery or outside of the operating room. The
      thrombotic risk associated with preoperative treatment interruption is too often
      overestimated. In practice, only patients at elevated risk should receive bridge
      therapy with standard or low-molecular-weight heparin. Patients with an INR less
      than 2 can undergo numerous surgical procedures. In the case of an immediate
      emergency in a patient treated with oral anticoagulants, perfusion with
      prothrombin complex is recommended. It is very effective and entails few risks.
      Vitamin K must be used as a complement, or alone in less urgent case, at a low
      dose (< 5 mg) and preferably orally. The phase of treatment resumption with a
      postoperative double treatment of heparin and oral anticoagulants must last long
      enough to avoid any thrombosis.

PMID- 17433616
TI  - [Perspectives in cardiac cell therapy].
AB  - The objective of cardiac cell therapy is to restore cardiac function in infarct
      zones. This therapy has been tested for two primary diagnoses: chronic heart
      failure and acute myocardial infarction. Clinical trials have showed that cardiac
      cell therapy is safe and that its results in terms of efficacy appear
      encouraging. Three challenges remain to obtain optimal therapeutic benefits:
      prevent the migration of these cells, increase their survival, and improve their
      integration into the recipient myocardium.

PMID- 17433617
TI  - [Mortality-morbidity conferences: evaluation of an intervention to expand their
      practice in a university hospital].
AB  - BACKGROUND: Mortality-morbidity conferences (M&MC) are a recognized technique for
      evaluating and improving medical practices as well as improving patient safety.
      OBJECTIVES: To describe the current practices for identification and management
      of care-related adverse events and to evaluate the effectiveness of an
      intervention to promote M&MC in a university hospital. METHODS: The study was
      designed as a before-and-after survey. In the first part of the survey (September
      December 2004), we interviewed the heads of the clinical departments and units in
      a Parisian university hospital (n=37), using a semi-structured questionnaire.
      Questions concerned the management of adverse events or errors in their
      departments or units. The intervention took place during these interviews and
      consisted of providing information on methods currently available to improve
      inpatient safety, including broad-based M&MC. The second part involved a
      structured questionnaire sent by e-mail in December 2005. RESULTS: In 2004, 24 of
      the 37 departments discussed adverse events, 11 kept a register of them, and 9
      used M&MC, mostly covering a specific limited segment of their specialty field.
      Only 2 used structured M&MC that covered the entire specialty field. In 2005, 3
      departments had expanded the field covered by their M&MC, and 9 had established
      M&MC for their entire field (n=12). Six departments had not changed the field of
      their M&MC and 14 had not introduced it. CONCLUSION: Our survey of department
      heads allowed us both to collect information about the methods they used for
      managing and evaluating adverse events and to provide information to them. This
      intervention may have contributed to increasing and improving the use of M&MC.

PMID- 17433618
TI  - Specificity of disgust sensitivity in the prediction of fear and disgust
      responding to a brief spider exposure.
AB  - This study examined the specificity of disgust sensitivity in predicting fear and
      disgust responses to exposure to a spider. Participants high (n=22) and low
      (n=28) in spider fear completed self-report measures of disgust sensitivity,
      contamination fear, anxiety, and negative affect. They then participated in a
      behavioral avoidance task (BAT) in which they were briefly exposed to a realistic
      looking, but fake, tarantula. Results revealed that disgust sensitivity was
      associated with fear and disgust responding to the BAT. The association between
      disgust sensitivity and disgust responding to the BAT remained significant after
      controlling for gender, spider fear group membership, contamination fear,
      anxiety, and negative affect. However, the association between disgust
      sensitivity and fear responding to the BAT was only marginally significant after
      controlling for the same variables. Contamination fear was also strongly related
      to fear and disgust responding to the BAT. However, this relationship was fully
      mediated by disgust sensitivity. These findings indicate that disgust sensitivity
      has a unique association with aversive responding to spiders. The implications of
      these findings for better understanding the complex role of fear and disgust as
      they related to disgust sensitivity in spider phobia are discussed.

PMID- 17433620
TI  - Enhancement of developmental toxicity effects of chemicals by gestational stress.
      A review.
AB  - Risk assessment of developmental toxicants is almost exclusively based on single
      chemicals studied in animals under controlled experimental conditions, as to
      reduce stress. Although humans may be exposed simultaneously to numerous hazards,
      little is known about the interaction of prenatal chemical exposures with other
      factors, such as maternal stress, itself a modifier of fetal development.
      Gestational stress has been hypothesized to enhance the developmental toxicity of
      chemicals. This review identified 36 animal studies investigating if maternal
      stress may enhance the effects of prenatal chemical exposure, and evaluated the
      presented hypothesis. Studies of a broad range of chemicals and developmental
      endpoints support the notion, that maternal stress is able to enhance the effects
      of developmental toxicants, although stress mitigated chemically induced effects
      in a few cases. Maternal stress most often enhanced chemical developmental
      toxicity at dose levels associated with severe maternal toxicity or where test
      agents were already above threshold for effect. Thus, LOAEL(chemical) was
      generally similar to LOAEL(chemical+stress), although not necessarily for the
      same endpoint. It should be noted that the database contained a limited number of
      studies, and only a single high dose level was applied in most studies, rendering
      establishment of NOAELs for combined exposures impossible. Furthermore, for some
      compounds, the margin between human exposure levels and the
      LOAEL(chemical+stress) seems small. Future studies are recommended to investigate
      compounds, for which maternal stress was already proven as an enhancer, at lower
      dose levels. Interactive response seems to depend on stressor severity and timing
      of chemical exposure relative to maternal stress which should be further
      scrutinized.

PMID- 17433619
TI  - Adolescent vs. adult-onset nicotine self-administration in male rats: duration of
      effect and differential nicotinic receptor correlates.
AB  - Adolescence is the life stage when tobacco addiction typically begins. Adolescent
      neurobehavioral development may be altered by nicotine self-administration in a
      way that persistently potentiates addiction. Previously, we showed that female
      adolescent rats self-administer more nicotine than do adults and that the
      increased nicotine intake then persists through the transition to adulthood [E.D.
      Levin, A. Rezvani, D. Montoya, J. Rose, H. Swartzwelder, Adolescent-onset
      nicotine self-administration modeled in female rats, Psychopharmacology 169
      (2003) 141-149.]. In the current study, male Sprague-Dawley rats were given
      access to nicotine via the standard operant IV self-administration procedure
      (nicotine bitartrate dose of 0.03 mg/kg/infusion). One group of male rats started
      during adolescence the other group started in young adulthood. After the end of
      the four-week period of self-administration brain regions of the rats were
      assessed for alpha4beta2 nicotinic receptor binding. We found that male rats,
      like females, show higher nicotine self-administration when starting during
      adolescence as compared to starting in adulthood (p<0.001). Indeed, the effect in
      adolescent males was even greater than that in females, with more than triple the
      rate of nicotine self-administration vs. the adult-onset group during the first 2
      weeks. The adolescent onset nicotine-self-administering rats also had
      significantly greater high affinity nicotinic receptor binding in the midbrain
      and the striatum, whereas hippocampal binding did not differ between the age
      groups. Striatal values significantly correlated with nicotine self
      administration during the first 2 weeks in the adult-onset group but not the
      adolescent-onset rats, suggesting that the differences in self-administration may
      depend in part on underlying disparities in synaptic responses to nicotine. After
      the initial 2 weeks, nicotine self-administration in male rats declined toward
      adult-like levels, as the adolescent rats approached adulthood. This study showed
      that adolescent male rats self-administer significantly more nicotine than do
      male adult rats, but that adolescent-onset nicotine self-administration in male
      rats declines over weeks of continued use to approach adult-onset levels. In a
      previous study, we found that female rats also show greater nicotine self
      administration with adolescent onset vs. adult onset, but that the females
      continued higher rates of self-administration into adulthood. Our results thus
      reinforce the concept that the adolescent brain is unusually receptive to the
      effects of nicotine in a manner that reinforces the potential for addiction.

PMID- 17433621
TI  - Association of serum concentrations of retinol and carotenoids with overweight in
      children and adolescents.
AB  - OBJECTIVE: A study was conducted to verify the association between serum
      concentrations of retinol and carotenoids with overweight in children and
      adolescents. METHODS: In total 471 children (7-9.9 y of age) and adolescents (10
      17 y of age), living in a poor region of the city of Rio de Janeiro, Brazil, were
      assessed. Serum concentrations of retinol and carotenoids were assessed by high
      performance liquid chromatography, and cutoffs for inadequacy of retinol and
      carotenoids were <30 and <40 microg/dL, respectively. Overweight was defined by
      the sex- and age-specific body mass index cutoffs recommended by World Health
      Organization. The logistic regression model was used to test the association of
      overweight, gender, and age range with low serum concentrations of retinol and
      carotenoids. RESULTS: Prevalences were 10% for low serum concentration of
      retinol, 55.8% for carotenoids, and 15.3% for overweight. Retinol inadequacy was
      significantly higher in adolescents (12.6%) than in children (6.8%). The average
      of carotenoids was significantly lower in overweight subjects (30.40 +/- 16.74
      versus 43.06 +/- 25.26 microg/dL, P = 0.001). Overweight children and adolescents
      presented a greater chance of a decrease in serum concentrations of carotenoids
      (odds ratio 2.51, 95% confidence interval 1.43-4.39) when compared with non
      overweight subjects. CONCLUSION: An important prevalence of vitamin A deficiency
      was found. Overweight children, as much as adolescents, may have a greater chance
      of presenting low concentrations of carotenoids and, hence, a lower antioxidant
      defense.

PMID- 17433622
TI  - Treatment of severe hypodontia-oligodontia--an interdisciplinary concept.
AB  - The authors' experience with oral rehabilitation of patients suffering from
      oligodontia (i.e. six or more congenitally missing permanent teeth, third molars
      excluded) is reported. The concept is based on an interdisciplinary team approach
      involving pedodontists, orthodontists, maxillofacial surgeons and
      prosthodontists. A series of 112 consecutive patients suffering from oligodontia
      were referred from 1997 to 2001. Ten of the patients (8.9%) suffered from
      ectodermal dysplasia. The total number of missing teeth was 1126, with an average
      of 10 per patient. Ninety-two patients had either finished treatment or were on
      an active treatment schedule. Of these, 97% underwent some kind of orthodontic
      treatment. Of the 112 patients, 51 had finished treatment at the end of the
      follow-up period (mean 28 months, range 1-68). Of these, fixed implant-supported
      prosthetic restoration was used in 90% to replace missing teeth, often combined
      with alveolar ridge augmentations (73%), sinus floor augmentation (43%), inferior
      alveolar nerve transposition (18%) and orthognathic surgery (27%). Early
      diagnosis, and comprehensive treatment planning with good coordination and timing
      of the individual treatment phases are decisive for a successful treatment
      outcome. The therapeutic concept is presented with special emphasis on surgical
      aspects.

PMID- 17433623
TI  - Monophasic epithelial synovial sarcoma arising in the temporomandibular joint.
AB  - Synovial sarcoma is a mesenchymal spindle-cell tumour that occurs infrequently in
      the head and neck. It originates from unknown stem cells differentiating into
      mesenchymal and/or epithelial structures. Most synovial sarcomas are biphasic in
      character, consisting of epithelial and spindle-cell elements. Here is reported a
      case of monophasic epithelial synovial sarcoma arising in the temporomandibular
      joint. The tumour was of a predominantly epithelial pattern, although a minute
      area of sarcomatous cells was found. The primary mode of treatment was wide en
      bloc excision. Two years after surgery, the patient died of hepatocellular
      carcinoma, but there was no evidence of synovial sarcoma recurrence.

PMID- 17433624
TI  - Lacosamide, a novel anti-convulsant drug, shows efficacy with a wide safety
      margin in rodent models for epilepsy.
AB  - This paper comprises a series of experiments in rodent models of partial and
      generalized epilepsy which were designed to describe the anti-convulsant profile
      of the functionalized amino acid lacosamide. Lacosamide was effective against
      sound-induced seizures in the genetically susceptible Frings mouse, against
      maximal electroshock test (MES)-induced seizures in rats and mice, in the rat
      hippocampal kindling model of partial seizures, and in the 6Hz model of
      psychomotor seizures in mice. The activity in the MES test in both mice (4.5mg/kg
      i.p.) and rats (3.9 mg/kg p.o.) fell within the ranges previously reported for
      most clinically available anti-epileptic drugs. At both the median effective dose
      for MES protection, as well as the median toxic dose for rotorod impairment,
      lacosamide elevated the seizure threshold in the i.v. pentylenetetrazol seizure
      test, suggesting that it is unlikely to be pro-convulsant at high doses.
      Lacosamide was inactive against clonic seizures induced by subcutaneous
      administration of the chemoconvulsants pentylenetetrazol, bicuculline, and
      picrotoxin, but it did inhibit NMDA-induced seizures in mice and showed full
      efficacy in the homocysteine model of epilepsy. In summary, the overall anti
      convulsant profile of lacosamide appeared to be unique, and the drug displayed a
      good margin of safety in those tests in which it was effective. These results
      suggest that lacosamide may have the potential to be clinically useful for at
      least the treatment of generalized tonic-clonic and partial-onset epilepsies, and
      support ongoing clinical trials in these indications.

PMID- 17433625
TI  - Association studies and functional validation or functional validation alone?

PMID- 17433627
TI  - Transcranial Magnetic Stimulation at M1 disrupts cognitive networks in
      schizophrenia.
AB  - Transcranial Magnetic Stimulation (TMS) is rapidly gaining acceptance as a non
      invasive probe into brain functionality. We utilize TMS to study the connectivity
      of a simple motor network in patients of schizophrenia (N=19), and in healthy
      control subjects (N=9). TMS was used in an externally paced finger tapping task,
      perturbing the internal network oscillations invoked by the finger motion as it
      keeps pace with a metronome. TMS perturbations were synchronized to the metronome
      and applied to the network at the level of the primary motor cortex (M1).
      Contrary to initial expectations, TMS did not affect the sensorimotor
      synchronization of subjects with schizophrenia or their tapping accuracy. TMS did
      cause extreme deviations in the finger's trajectory, and altered the timing
      perceptions of subjects with schizophrenia. Additionally, it invoked high-level
      deficiencies related to attention and volition in the form of lapses, implying
      that the connectivity between modules in the brain that underlie motor control,
      sensorimotor synchronization, timing perception and awareness of action, can be
      disrupted by TMS in subjects with schizophrenia, but not in healthy subjects. The
      ability to disrupt high level network functions with perturbations to the lower
      level of M1 supports models describing deficits in connectivity of distributed
      networks in the brains of schizophrenia patients. It also demonstrates the use of
      TMS to probe connectivity between components of such networks.

PMID- 17433626
TI  - Abnormalities of cingulate gyrus neuroanatomy in schizophrenia.
AB  - OBJECTIVE AND METHODS: Abnormalities of the neuroanatomy of the gray matter of
      the cingulate gyrus, especially its anterior segment, have been suggested to be
      an important characteristic of schizophrenia. In this study, T1-weighted magnetic
      resonance scans were collected in 53 individuals with schizophrenia and 68
      comparison subjects matched for age, gender, race and parental socioeconomic
      status. We applied Labeled Cortical Mantle Distance Mapping to assess the volume,
      surface area and thickness of the cortical mantle within the anterior (AC) and
      posterior (PC) segments of the cingulate gyrus, excluding the paracingulate
      gyrus, and related these anatomical measures to measures of psychopathology and
      illness duration. RESULTS: After covarying for total cerebral volume, individuals
      with schizophrenia showed smaller AC gray matter volume (p=0.024), thickness
      (trend, p=0.081), but not surface area (p=0.16), than comparison subjects.
      Similar group differences were found for PC gray matter volume (p=0.0005) and
      thickness (trend, p=0.055), but not surface area (p=0.15). Across both groups,
      there was a significant L>R asymmetry in thickness of the AC, and a significant
      L>R asymmetry in the surface area of the PC. However, there were no significant
      group-by-hemisphere interactions. In the individuals with schizophrenia, thinning
      of the AC, but not the PC, was correlated with a longer duration of illness and a
      greater severity of psychotic symptoms. CONCLUSIONS: Individuals with
      schizophrenia showed smaller gray matter volumes across the entire cingulate
      gyrus, mostly due to a reduction in cortical mantle thickness. However,
      structural measures of the AC were more closely related to clinical features of
      the illness.

PMID- 17433628
TI  - Reduced posterior nasal cavity volume: a gender-specific neurodevelopmental
      abnormality in schizophrenia.
AB  - OBJECTIVE: We previously reported that men with schizophrenia had reduced volumes
      of the posterior nasal cavity bilaterally. Since the nasal cavities develop in
      conjunction with both the palate and ventral forebrain, this could represent a
      simple marker of embryological dysmorphogenesis contributing to schizophrenia.
      The current study expands on this finding by examining a larger sample of both
      male and female patients and unaffected 1st-degree relatives, to determine the
      gender distribution of this abnormality and the extent to which it may be
      genetically mediated. METHOD: A measurement of nasal volume and geometry was
      acquired by acoustic rhinometry for 85 schizophrenia patients, 25 unaffected 1st
      degree relatives of schizophrenia probands and 66 healthy comparison subjects.
      RESULTS: Male patients had smaller posterior nasal volumes than both male control
      subjects and male relatives. However, female patients did not differ from either
      female controls or female family members. Unaffected 1st-degree relatives did not
      differ from same-sex control subjects. These findings persisted after covarying
      for height and smoking history, and were unrelated to clinical symptomatology or
      antipsychotic medication usage. CONCLUSION: Posterior nasal cavity volume
      decrement appears to be a specific developmental craniofacial abnormality that
      may reflect an early disruption in embryological development in males with
      schizophrenia. Although further study is needed, this may be a marker of a
      "second hit" that distinguishes genetically vulnerable men who go on to develop
      the illness from those who do not.

PMID- 17433630
TI  - Characterization of AT1 and AT2 receptor expression profiles in human skin during
      fetal life.

PMID- 17433629
TI  - Validity of a 'proxy' for the deficit syndrome derived from the Positive And
      Negative Syndrome Scale (PANSS).
AB  - Schizophrenia patients with the deficit syndrome (DS) may represent a homogeneous
      subgroup. To increase the practicability of diagnosing the DS, Kirkpatrick et al.
      [Kirkpatrick, B., Buchanan, RW., Breier, A. Carpenter, WT., 1993. Case
      identification and stability of the deficit syndrome of schizophrenia. Psychiatry
      Res. 47, 47-56.] proposed the use of a 'proxy' case identification tool using
      standardized symptom ratings instead of the Schedule for the Deficit Syndrome
      (SDS) which requires an independent clinical assessment. The Proxy for the
      Deficit Syndrome (PDS) is based on the extraction of symptoms that are
      essentially equivalent or overlap substantially with the restricted affect and
      diminished emotional range on the SDS. Kirkpatrick et al. [Kirkpatrick, B.,
      Buchanan, RW., Breier, A. Carpenter, WT., 1993. Case identification and stability
      of the deficit syndrome of schizophrenia. Psychiatry Res. 47, 47-56.] reported
      good sensitivity and specificity in a comparison of SDS and PDS assessments among
      100 chronic schizophrenia outpatients. The present investigation involves the
      comparison of the deficit syndrome as assessed by the "gold standard" Schedule
      for the Deficit Syndrome with the ratings of the same symptoms embodied in the
      "proxy instrument" the PANSS, within the same group of 156 inpatients. Forty-four
      patients were assessed by the SDS to have the deficit syndrome. Patients with and
      without the DS, as defined by the SDS, did not differ for age, education, age at
      illness onset and duration of illness. The two main 'proxy' measures PDS1 and
      PDS2 discriminated across the SDS groups. The direct dichotomous comparison of
      the actual SDS and the 'proxy' derived PDS groups demonstrated good specificity
      (78.6% and 79.5%) and moderate to very good sensitivity (61.4% and 86.4%) and
      there was a moderately low rate of false positive cases (21.4% and 20.5%). For
      the two main 'proxy' measures (PDS1 and PDS2) kappas were .38 and .59,
      representing poor to good agreement. In our sample of rigorously diagnosed
      schizophrenia inpatients, the use of a 'proxy' case identification tool for the
      deficit syndrome would appear to be a viable alternative in identifying a
      subgroup of schizophrenia patients with the deficit syndrome when the use of the
      actual SDS is not feasible. Further study is indicated before the PDS as
      extracted from the PANSS can be used in lieu of the SDS for identifying patients
      with this syndrome.

PMID- 17433631
TI  - Evaluation of gatifloxacin pharmacokinetics and pharmacodynamics in severely ill
      adults in a medical Intensive Care Unit.
AB  - A prospective, open-label study investigated the steady-state pharmacokinetics of
      gatifloxacin in 20 adult patients in a medical Intensive Care Unit (ICU). Twelve
      patients had normal or moderately impaired renal function (creatinine clearance
      (CrCL) >or=40 mL/min) and received gatifloxacin 400 mg intravenously once daily.
      Eight patients had CrCL<40 mL/min and received 200 mg doses. Gatifloxacin plasma
      and urine concentrations were determined by validated high-performance liquid
      chromatography. Mean+/-standard deviation gatifloxacin elimination half-life
      (t(1/2)), systemic clearance and volume of distribution in patients with
      CrCL>or=40 mL/min were 10.8+/-1.5h, 156+/-29 mL/min and 1.8+/-0.2 L/kg,
      respectively. Maximum and minimum serum concentrations (C(max) and C(min)) and
      area under the serum concentration-time curve from 0-24 h (AUC(0-24)) in these
      patients were 4.77+/-0.76 mg/L, 1.08+/-0.28 mg/L and 44.4+/-9.2 mgh/L,
      respectively. Observed t(1/2), C(max) and AUC(0-24) following 200 mg doses in
      patients with poor renal function (CrCL<40 mL/min) were 18.2+/-3.3 h, 2.85+/-0.76
      mg/L and 36.6+/-3.4 mgh/L, respectively. Statistically significant (P<0.05)
      increase in AUC(0-24) and decreases in t(1/2) and clearance (total and renal)
      were observed in ICU patients administered intravenous gatifloxacin compared with
      previous data in healthy volunteers. Pharmacodynamic evaluation by Monte Carlo
      simulation indicated that approved gatifloxacin dosage regimens appear to be
      adequate for most pathogens (minimum inhibitory concentration (MIC) <or=0.5
      microg/mL) associated with community-acquired infections in severely ill ICU
      patients; less susceptible pathogens (MIC>or=1 microg/mL) do not appear to be
      optimally treated with currently approved doses.

PMID- 17433633
TI  - Effects of copper on dielectric properties of E. coli cells.
AB  - Dielectric properties of E. coli cells before and after Cu(2+) incubation were
      investigated by using the dielectric spectroscopic technique. The dielectric
      spectra are analyzed theoretically by means of the extended three-shell
      ellipsoidal model, which can reflect the complicated morphological structure of
      E. coli cell including the outer membrane, the periplasmic space, the inner
      membrane and the cytoplasm. The results showed that dielectric properties of
      these cellular components were changed with Cu(2+) treatment in a time- and
      concentration-dependent way. The permttivity of the outer membrane increased with
      the incubation time and concentration of Cu(2+), possibly because polarizability
      of the outer leaflet of lipopolysaccharides was affected by Cu(2+). The
      conductivity of the periplasmic space decreased with the incubation time and
      concentration of Cu(2+), possibly due to the damage of peptidoglycan. The
      decreased permittivity of the inner membrane may be caused by disturbance of the
      lipid bilayer structure produced by Cu(2+) incubation. The decreased cytoplasmic
      conductivity may be the consequence of the leakage of K(+) from it. The
      cytoplasmic permittivity decreased with Cu(2+) treatment probably because of the
      leakage of its some components.

PMID- 17433632
TI  - Cardiac expression of the Drosophila Sulphonylurea receptor gene is regulated by
      an intron enhancer dependent upon the NK homeodomain factor Tinman.
AB  - Cardiac development proceeds via the activation of a complex network of
      regulatory factors which both directly and indirectly impact downstream cardiac
      structural genes. In Drosophila, the NK homeodomain transcription factor Tinman
      is critical to cardiac specification and development via the activation of a
      number of key regulatory genes which mediate heart development. In this
      manuscript, we demonstrate that Tinman also functions in Drosophila to directly
      activate transcription of the ATP binding cassette gene Sulphonylurea receptor
      (Sur). Cardiac expression of Sur is regulated by Tinman via an intron enhancer
      which first becomes active at stage 12 of embryogenesis, and whose function is
      restricted to the Tin cardial cells by the end of embryogenesis. Cardiac Sur
      enhancer activity subsequently persists through larval and adult development, but
      interestingly becomes modulated in several unique subsets of Tin-expressing
      cardial cells. The cardiac enhancer contains four binding sites for Tinman
      protein; mutation of two of these sites significantly reduces enhancer activity
      at all stages of development, and activation of the wild-type enhancer by ectopic
      Tinman protein confirms Sur is a direct target of Tinman transcriptional
      activation. These findings delineate at the molecular level specific sub-types of
      Tin cardial cells, and define an important regulatory pathway between two
      Drosophila genes for which mutations in human homologs have been shown to result
      in cardiac disease.

PMID- 17433634
TI  - Effects of block length on the enzymatic degradation and erosion of oxazoline
      linked poly-epsilon-caprolactone.
AB  - The aim of the study was to develop enzyme sensitive polymers for pharmaceutical
      applications. Thus, 2,2'-bis(2-oxazoline)-linked poly-epsilon-caprolactone (PCL
      O) polymers were synthesized by using epsilon-caprolactone precursors with
      different molecular weights (M(n): 1500, 3900, 7500 and 12,000g/mol), and the
      effects of PCL block length on enzymatic degradation and erosion (weight loss) of
      PCL-O films were studied. Solvent cast PCL and PCL-O films were incubated (22
      days) in the presence of pancreatin (1%, pH 7.5), with and without enzyme
      inhibitors. In the absence of enzyme inhibitors, surface erosion of the PCL-O
      films occurred during incubation, and the erosion of the PCL-O films increased in
      parallel with a decrease in the PCL block length. The presence of the lipase
      inhibitors, paraoxon-ethyl and tetrahydrolipstatin delayed the weight loss of the
      PCL-O films. These results indicate that lipase was mainly responsible for the
      enzymatic erosion of the PCL-O films. In comparison, practically no weight loss
      of the PCL or the PCL-O films was observed in phosphate buffer (pH 7.4) (28 days
      incubation). The results demonstrate that the studied epsilon-caprolactone based
      poly(ester-amide)s are enzyme sensitive polymers whose erosion rate can be
      controlled by the PCL block length.

PMID- 17433635
TI  - [Why asthma remains undertreated? Evidence to support one's argument].

PMID- 17433636
TI  - [Why is asthma still an undertreated disease: the fault of the doctor?].

PMID- 17433637
TI  - The hypoxic tumour microenvironment, patient selection and hypoxia-modifying
      treatments.
AB  - Tumour hypoxia has been found to be a characteristic feature in many solid
      tumours. It has been shown to decrease the therapeutic efficacy of radiation
      treatment, surgery and some forms of chemotherapy. Successful approaches have
      been developed to counteract this resistance mechanism, although usually at the
      cost of increased short- and long-term side-effects. New methods for qualitative
      and quantitative assessment of tumour oxygenation have made it possible to
      establish the prognostic significance of tumour hypoxia. The ability to determine
      the degree and extent of hypoxia in solid tumours is not only important
      prognostically, but also in the selection of patients for hypoxia-modifying
      treatments. To provide the best attainable quality of life for individual
      patients it is of increasing importance that tools be developed that allow a
      better selection of patients for these intensified treatment strategies. Several
      genes and proteins involved in the response to hypoxia have been identified as
      potential candidates for future use in predictive assays. Although some markers
      and combinations have shown potential benefit and are associated with treatment
      outcome, their clinical usefulness needs to be validated in prospective trials. A
      review of published studies was carried out, focusing on the assessment of tumour
      hypoxia, patient selection and the possibilities to overcome hypoxia during
      treatment.

PMID- 17433639
TI  - C-reactive protein is directly related to plasminogen activator inhibitor type 1
      (PAI-1) levels in diabetic subjects with the 4G allele at position -675 of the
      PAI-1 gene.
AB  - BACKGROUND AND AIMS: C-reactive protein (CRP) has been identified as a possible
      factor able to promote atherosclerosis. "In vitro" studies have demonstrated that
      CRP induces plasminogen activator inhibitor type 1 (PAI-1) expression, suggesting
      a hypofibrinolytic role for CRP. As CRP and PAI-1 levels increase in type 2
      diabetic subjects, we decided to study the relationship between CRP and PAI-1,
      and the role of the 4G/5G polymorphism of the PAI-1 gene on this relationship in
      a diabetic population without complications. METHODS AND RESULTS: Two hundred and
      ninety-five type 2 diabetic patients (age 60.9+/-10.5 years) and 290 healthy
      controls (age 59.2+/-11.5 years) were enrolled. A significant correlation between
      PAI-1 and CRP in diabetic subjects was found (r=0.45, p<0.001), whereas no
      relationship was evident in the control subjects between these inflammatory
      markers. Multiple regression analysis highlighted that CRP is the only one
      significant variable of PAI-1 antigen in diabetic subjects (partial r=0.31,
      p<0.01). Stratifying by genotype, a positive correlation between PAI-1 and CRP in
      4G/4G (partial r=0.64 p<0.001) and 4G/5G (partial r=0.47, p<0.001) subjects was
      found, whereas no correlation in 5G/5G was present. Multiple regression analysis
      confirmed the presence of this correlation in 4G/4G (partial r=0.45, p<0.001) and
      in 4G/5G (partial r=0.34, p=0.007) diabetic patients. CONCLUSIONS: These findings
      demonstrate that CRP plays an important role in the complex mechanism regulating
      PAI-1 antigen in 4G diabetic carriers.

PMID- 17433638
TI  - A multicenter Italian study on pregnancy outcome in women with diabetes.
AB  - BACKGROUND AND AIM: To determine pregnancy outcome in women with type 1 and type
      2 diabetes. METHODS AND RESULTS: A prospective study was conducted in 33 centers
      in Italy between 1999 and 2003, mainly recording preterm delivery, stillbirths,
      neonatal mortality, congenital malformations and birthweight. Of the 668 women
      examined, 504 had type 1 diabetes and 164 had type 2. Pre-pregnancy counseling
      had been provided to 43.9% of the women who had type 1 diabetes and 29.1% of the
      women who had type 2 diabetes and correlated with a better HbA1c value throughout
      pregnancy. The preterm delivery rate was significantly higher in type 1 and 2
      diabetics than in normal pregnant women and was related to HbA1c values higher
      than 8%, gestational hypertension, pre-eclampsia and the presence of retinopathy
      before pregnancy. The stillbirth and neonatal mortality rates were also higher in
      diabetic pregnant women (1.26% and 0.63%, respectively) than in Italian
      pregnancies in general (0.30% and 0.32%), and the same was true for major
      congenital malformations (4.9% for diabetic pregnancies, 0.86% for normal Italian
      pregnancies). CONCLUSIONS: In our population, pregnancy in diabetic women was
      still associated with a high rate of stillbirths, neonatal mortality and
      congenital malformations. Unplanned pregnancies and non-optimal glycemia control
      may help explain the high rates of maternal and neonatal complications.

PMID- 17433640
TI  - The impact of the menopause on coronary artery calcification examined by
      multislice computed tomography scanning.
AB  - BACKGROUND AND AIMS: To examine whether there is a difference in coronary artery
      calcification (CAC) scores between males and females aged above 50 years. METHODS
      AND RESULTS: A total of 479 subjects aged between 40 and 70 years with no
      clinical or family history of cardiovascular disease (CVD) were enrolled for this
      study. All subjects were assessed by multislice CT scanning (MCTS), and the CAC
      scores obtained were assigned to one of four quartiles for further assessment and
      comparison. The main outcome evaluated was the percentage of high CAC scores and
      mean CAC scores, comparing males and females of different age groups. This study
      found that the percentage of high CAC scores increased markedly from 5% (40-49
      age group) to 21.2% (50-59 age group) among females. The increase was
      significantly less when comparing males from different age groups (from 25% in
      the 40-49 age group to 31.2% in the 50-59 age group). Females had higher odds
      ratios (ORs) postmenopausally (4.3 in the 50-59 age group) than males in the same
      age group (1.6). CONCLUSIONS: These initial findings seem to indicate that above
      50 years of age, CAC is more dependent on age in females than in males, which
      might be due to the effect of the menopause.

PMID- 17433641
TI  - Comparative study of doxorubicin-loaded poly(lactide-co-glycolide) nanoparticles
      prepared by single and double emulsion methods.
AB  - This study describes how the control of doxorubicin (DOX) polarity allows to
      encapsulate it inside poly(lactide-co-glycolide) (PLGA) nanoparticles formulated
      either by a single oil-in-water (O/W) or a double water-in-oil-in-water (W/O/W)
      emulsification method (SE and DE, respectively). DOX is commercially available as
      a water soluble hydrochloride salt, which is useful for DE. The main difficulty
      related to DE approach is that the low affinity of hydrophilic drugs to the
      polymer limits entrapment efficiency. Compared to DE method, SE protocol is
      easier and should provide an additional gain in entrapment efficiency. To be
      encapsulated by SE technique, DOX should be used in a more lipophilic molecular
      form. We evaluated the lipophilicity of DOX in terms of apparent partition
      coefficient (P) and modulated it by adjusting the pH of the aqueous phase. The
      highest P values were obtained at pH ranging from 8.6 to 9, i. e. between two DOX
      pK(a) values (8.2 and 9.6). The conditions favorable for the drug lipophilicity
      were then used to formulate DOX-loaded PLGA nanoparticles by SE method. DOX
      encapsulation efficiency as well as release profiles were evaluated for these
      nanoparticles and compared to those with nanoparticles formulated by DE. Our
      results indicate that the encapsulation of DOX in nanoparticles formulated by SE
      provides an increased drug entrapment efficiency and decreases the burst effect.

PMID- 17433642
TI  - Skin permeation of ketotifen applied from stick-type formulation.
AB  - A stick-typed long lasting device for both transdermal and topical drug delivery
      has been developed. Ketotifen fumarate (KT) was used as a model drug. The effect
      of a variety of permeation enhancers was investigated using hairless mouse skin
      in vitro. Polyoxyethylene oleyl ether (POE), among the enhancers used, most
      enhanced the skin permeation of KT. The permeation enhancement was mainly due to
      the increase in the drug solubility in the stratum corneum and the resulting
      increase in the partition coefficient. The rate of skin permeation of KT was
      approximately proportional to the loading dose of the drug.

PMID- 17433643
TI  - A protein linkage map of the ESAT-6 secretion system 1 (ESX-1) of Mycobacterium
      tuberculosis.
AB  - Tuberculosis is a chronic infectious disease caused by bacteria of the
      Mycobacterium tuberculosis complex. One of the major contributors to virulence
      and intercellular spread of M. tuberculosis is the ESAT-6 secretion system 1 (ESX
      1) that has been lost by the live vaccines Mycobacterium bovis BCG (Bacille
      Calmette Guerin) and Mycobacterium microti as a result of independent deletions.
      ESX-1 consists of at least 10 genes (Rv3868-Rv3877) encoding the T-cell antigens
      ESAT-6 and CFP-10 as well as AAA-ATPases, chaperones, and membrane proteins which
      probably form a novel export system. To better understand the mode of action of
      the ESX-1 proteins, as a prelude to drug development, we examined systematically
      the interactions between the various proteins using the two-hybrid system in
      Saccharomyces cerevisiae. Interestingly, ESAT-6 and CFP-10 formed both hetero-
      and homodimers. Moreover, Rv3866, Rv3868, and CFP-10 interacted with Rv3873 which
      also homodimerized. The data were summarized in a protein linkage map that is
      consistent with the model for the secretion apparatus and can be used as a basis
      to identify inhibitors of specific interactions.

PMID- 17433644
TI  - Study on the diversity of endophytic communities from rice (Oryza sativa L.) and
      their antagonistic activities in vitro.
AB  - Endophytic populations were isolated from 2400 segments of Oryza sativa collected
      from Bhadra River Project Area, Southern India during December 2005 (Winter) and
      April 2006 (Summer). Overall colonization rates from surface sterilized tissues
      were 40.3% in roots and 25.83% in leaves during winter season, 20.15% in roots
      and 8.66% in leaves during summer season. Nineteen different fungal taxa, a
      Streptomyces sp. and bacterial species were isolated. Streptomyces sp.,
      Chaetomium globosum, Penicillium chrysogenum, Fusarium oxysporum and Cladosporium
      cladosporioides were dominant endophytes in this study. Frequency of colonization
      between the sites, seasons and rice varieties were found to differ significantly.
      Dual culture studies revealed that C. globosum, P. chrysogenum and Streptomyces
      sp. are suitable candidates for extraction of biologically active compounds. Rice
      harbors many endophytic organisms and some of them have antagonistic properties
      against fungal pathogens.

PMID- 17433645
TI  - The effect of prostaglandin E2 on transcriptional responses of Candida albicans.
AB  - Prostaglandins are hormone-like chemicals involved in the inflammatory response
      and in defense against pathogens. We investigated the effect of extracellular
      prostaglandin E2 (PGE2) on the human fungal pathogen Candida albicans.
      Transcriptional analysis of C. albicans treated with PGE2 indicated differential
      expression of genes involved in alternative carbon source catabolism, and showed
      repression of genes encoding components of both the translational machinery and
      the homolog of Saccharomyces cerevisiae Mac1 regulon needed for iron uptake.
      Prostaglandin-mediated repression of the Mac1 regulon required the Tup1p
      transcriptional regulator, and did not occur in hyphal cells. Analysis of the
      promoter of the Mac1 regulon component FRE7 revealed a well-conserved palindromic
      Mac1p binding site that was critical for expression of a downstream reporter. To
      identify elements other than Tup1 that are involved in regulation of the Mac1
      regulon, we screened a C. albicans transcription factor mutant library with this
      FRE7 promoter fused to a lacZ reporter. Oaf1p, Stp4p, Azf1p, and Cas1p mutants
      showed moderate enhancement of reporter expression. Azf1p and Cas1p were shown to
      be transducers of the PGE2 dependent signaling pathway.

PMID- 17433646
TI  - Modulation of radiation-induced biochemical alterations in mice by rosemary
      (Rosemarinus officinalis) extract.
AB  - Radioprotective effect of leaves extract of Rosemarinus officinalis (ROE) has
      been studied against 6 Gy gamma-radiations in the liver of Swiss albino mice at
      various post-irradiation intervals between 12 h and 30 days. In control animals
      (without ROE treated irradiated), an elevation in glycogen, protein, acid and
      alkaline contents was found till day 5th, but thereafter decreased at successive
      intervals without returning to normal. Cholesterol level was found to be lower
      than normal till 10th day, then increased up to 20th day but later declined
      without restoring normal level. A similar trend of variation in these biochemical
      parameters was observed in experimental group (ROE pretreated irradiated) also
      but to a lower extent. ROE significantly delayed and inhibited the rise in these
      biochemical parameters. Almost normal values of such constituents were regained
      by day 30th in experimental animals; whereas in control animals, normal values
      were not ever attained. In control animals, there was an elevation in lipid
      peroxidation (LPx) and a decrease in glutathione (GSH) in blood and liver;
      whereas in experimental group, decline in LPx accompanied by an increase in GSH
      concentration was observed.

PMID- 17433647
TI  - ACE activity during the hypotension produced by standardized aqueous extract of
      Cecropia glaziovii Sneth: a comparative study to captopril effects in rats.
AB  - To evaluate the effect of the standardized aqueous extract (AE) of Cecropia
      glaziovii Sneth on the plasma angiotensin I converting enzyme (ACE-EC 3.4.15.1)
      activity, rats were treated with a single dose of AE (1 g/kg, p.o.) or repeatedly
      (0.5 g/kg/bid, p.o.) for 60 days. Captopril (50 mg/kg, p.o.) was used as positive
      control on the same animals. The effects on the blood pressure were recorded
      directly from the femoral artery (single dose), or indirectly by the tail cuff
      method (repeated doses) in conscious rats. The plasma ACE activity was determined
      spectrofluorimetrically using Hypuril-Hystidine-Leucine as substrate. The
      arterial blood pressure, heart rate and plasma ACE activity were not
      significantly modified within 24 h after a single dose administration of AE.
      Comparatively, blood pressure in captopril treated rats was reduced by 7-16% and
      heart rate was increased by 10-20% from 30 min to 24 h after drug administration.
      ACE activity after captopril presented a dual response: an immediate inhibition
      peaking at 30 min and a slow reversal to 32% up-regulation after 24 h. To
      correlate the drug effects upon repeated administration of either compound,
      normotensive rats were separated in three groups: animals with high ACE (48.8+/
      2.6 nmol/min/ml), intermediate ACE (39.4+/-1.4 nmol/min/ml) and low ACE (23.5+/
      0.6 nmol/min/ml) activity, significantly different among them. Repeated treatment
      with AE reduced the mean systolic blood pressure (121.7+/-0.5 mm Hg) by 20 mm Hg
      after 14 days. The hypotension was reversed upon washout 60 days afterwards.
      Likely, repeated captopril administration decreased blood pressure by 20 mm Hg
      throughout treatment in all groups. After 30 days treatment with AE (0.5
      g/kg/bid, p.o.) the plasma ACE activity was unchanged in any experimental group.
      After captopril (50 mg/kg/bid, p.o.) administration the plasma ACE activity was
      inhibited by 50% within 1 h treatment but it was up-regulated by 120% after 12 h
      in all groups. It is concluded that the hypotension produced by prolonged
      treatment with AE of C. glaziovii is unrelated to ACE inhibition.

PMID- 17433648
TI  - WITHDRAWN: New Community herbal monographs.

PMID- 17433649
TI  - Antioxidant activities of Ptychopetalum olacoides ("muirapuama") in mice brain.
AB  - Ptychopetalum olacoides (PO) roots are used by Amazonian peoples to prepare
      traditional remedies for treating various central nervous system conditions in
      which free radicals are likely to be implicated. Following the identification of
      PO ethanol extract (POEE) free-radical scavenging properties in vitro, the aim of
      this study was to verify the in vivo antioxidant effect of POEE. Aging mice (14
      months) were treated (i.p.) with saline, DMSO (20%) or POEE (100mg/kg body wt.),
      and the hippocampi, cerebral cortex, striata, hypothalamus and cerebellum
      dissected out 60 min later to measure antioxidant enzyme activities, free-radical
      production and damage to macromolecules. POEE administration reduced free-radical
      production in the hypothalamus, lead to significant decrease in lipid
      peroxidation in the cerebral cortex, striatum and hypothalamus, as well as in the
      carbonyl content in cerebellum and striatum. In terms of antioxidant enzymes,
      catalase activity was increased in the cortex, striatum, cerebellum and
      hippocampus, while glutathione peroxidase activity was increased in the
      hippocampus. This study suggests that POEE contains compounds able to improve the
      cellular antioxidant network efficacy in the brain, ultimately reducing the
      damage caused by oxidative stress.

PMID- 17433650
TI  - Differentiation and function of Th17 T cells.
AB  - IL-17-producing T cells have recently been classified as a new effector T-cell
      subset, termed Th17, which is distinct from Th1, Th2 and Treg subsets. There has
      been much progress in the past year, leading to identification of the molecular
      mechanisms that drive differentiation of Th17 T cells. This has helped to clarify
      many aspects of their role in host defense as well as in autoimmunity.
      Nevertheless, many intriguing questions remain to be answered regarding the
      regulation of Th17-mediated responses as well as their interactions with the
      other T-cell subsets. Furthermore, the role of pathogens and pathogen-derived
      molecules in influencing effector T-cell polarization needs to be re-evaluated in
      the light of the differentiation conditions that favor Th17 T-cell responses.

PMID- 17433651
TI  - Affinity of antigen encounter and other early B-cell signals determine B-cell
      fate.
AB  - Three possible effector fates await the naive follicular B cell following antigen
      stimulation in thymus-dependent reactions. Short-lived plasma cells produce an
      initial burst of germline-encoded protective antibodies, and long-lived plasma
      cells and memory B cells arise from the germinal center and function to enhance
      and sustain the humoral immune response. The inherent B-cell receptor affinity of
      naive follicular B cells and the contribution of other early B-cell signals pre
      determines the pattern of transcription factor expression and the differentiation
      path taken by these cells. High initial B-cell receptor affinity shunts naive
      follicular B-cell clones towards the short-lived plasma cell fate, whereas modest
      affinity clones are skewed towards a plasma cell fate and low-affinity clones are
      recruited into the germinal center and are selected for both long-lived plasma
      cells and memory B cell pathways. In the germinal center reaction, increased
      levels of the transcription factor interferon regulatory factor-4 drive the
      molecular program that dictates differentiation into the long-lived plasma cell
      phenotype but has no impact on the memory B cell compartment. We hypothesize that
      graded interferon regulatory factor-4 levels driven by signals to B cells,
      including B-cell receptor signal strength, are responsible for this branch point
      in the B-cell terminal differentiation pathway.

PMID- 17433652
TI  - Genetic defects affecting lymphocyte cytotoxicity.
AB  - Cytolytic lymphocytes kill virus-infected cells as well as tumor cells by the
      exocytosis of the content of specialized secretory lysosomes at the immunological
      synapse (IS). Perforin and granzymes are the molecular effectors that induce
      rapid target cell death. Cytolytic T cells are activated by specific antigen
      recognition whereas the cytolytic activity of natural killer cells is initiated
      by specific activating receptors or combinations thereof and is inhibited by self
      MHC class I recognition. The cytolytic process has received considerable
      attention and can now be described as a multi-step process including cell
      activation, polarization of specialized lysosomes -- lytic granules -- toward the
      IS, tethering of the lytic granules to the plasma membrane, priming for fusion
      with the plasma membrane, effective fusion and release of granule content in the
      IS cleft, and death of the target. This is a highly flexible system that could
      enable a cytolytic cell to subsequently kill target cells bound at different
      sites around the effector cell. Cytolytic cells exert a second effector function
      consisting of the secretion of cytokines, notably interferon gamma. The latter
      secretory process functions independently from the exocytic pathway of the lytic
      granules.

PMID- 17433653
TI  - Effect of inhaled corticosteroids on forearm bone mineral density: the HUNT
      study, Norway.
AB  - PURPOSE: To study the effect of inhaled corticosteroid (ICS) on bone mineral
      density (BMD) in an observational longitudinal study. METHODS: In 1995-97, as
      part of the Nord-Trondelag Health Study, Norway, 10,941 subjects aged 20 yr or
      more, either reporting asthma diagnosis/asthma-related symptoms or randomly
      selected, were interviewed, underwent spirometry and had their forearm BMD
      assessed. Among these, 4705 persons were invited to follow-up interview and bone
      densitometry in 2001; a total of 2848 subjects were eligible for analyses.
      RESULTS: Use of corticosteroids for respiratory diseases was reported by 1262
      subjects, and 528 subjects had used ICS at both baseline and follow-up. The
      yearly loss of adjusted forearm distal BMD was higher in those reporting use of
      ICS at both baseline and follow-up compared to subjects without respiratory
      symptoms. In women the figures were 3.14 versus 2.26 mg/cm2, whilst in men they
      were 3.76 versus 1.92 mg/cm2 (both p<0.01). No significant association was found
      between loss of BMD and neither daily dose nor duration of ICS use. Reduced lung
      function (forced expiratory flow in 1s) was an independent risk factor for
      increased bone loss in both sexes. CONCLUSIONS: ICS users had greater bone loss
      at the forearm compared to ICS naive persons, but no significant dose-response
      effect between ICS and BMD was found. Residual confounding by disease severity
      cannot be ruled out, but even in case of an ICS causal effect, this should have
      minor clinical significance in most patients using low to moderate doses of ICS.

PMID- 17433654
TI  - CC ligand 2 levels are increased in LPS-stimulated peripheral monocytes of
      patients with non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) shows a particular aggressive behaviour.
      Tumour associated macrophages (TAMs) play an important role in tumour growth and
      progression and CC ligand 2 (CCL2)/CCR2 axis is markedly involved in their
      recruitment in the tumour mass from the circulation. The aim of this study was to
      determine the plasma levels of CCL2 and the expression of CCR2 in the peripheral
      blood mononuclear cells (PBMCs) of 18 smokers with NSCLC, eight healthy smokers
      and nine non-smokers. Then, we investigated CCL2 levels in the supernatants of
      unstimulated and LPS-stimulated PBMC cultures of the same groups of patients.
      CCL2 levels in plasma and supernatants of PBMC cultures were determined by ELISA.
      CCR2 expression in PBMC cytospins was assessed by immunocytochemistry. CCL2
      plasma levels and CCR2 expression by PBMCs were similar in patients with NSCLC,
      healthy smokers and non-smokers. In the supernatants of unstimulated PBMC
      cultures, CCL2 content was not different between the three groups of subjects.
      Supernatants of LPS-stimulated PBMCs of NSCLC patients showed a higher content of
      CCL2 as compared to supernatants of non-smokers (p<0.005). CCL2 content increased
      28.5-fold vs baseline production in the group of NSCLC patients, 15-fold in
      healthy smokers and 13-fold in the group of non-smokers. In conclusion, after LPS
      stimulation, PBMCs of patients with NSCLC release higher levels of CCL2 as
      compared to those of non-smokers, supporting the hypothesis of a CCL2 involvement
      in NSCLC biology.

PMID- 17433655
TI  - Higher pH and faster decomposition in biowaste composting by increased aeration.
AB  - Composting of source separated municipal biowaste has at several plants in
      Scandinavia been hampered by low pH. In this study the hypothesis that increased
      aeration would improve the process was tested in full-scale experiments at two
      large composting plants. The O2 concentrations were high (>15%) even at the low
      aeration rates, so the prevailing low pH was not due to an anaerobic process
      environment. In spite of this, increased aeration rates at the start of the
      process resulted in higher microbial activity, increased pH and a more stable
      compost product. At one plant the decomposition rate varied in proportion to the
      aeration rate, to the extent that the temperatures and O2 concentrations were
      similar during the early processes even though aeration rates varied between 10
      and 50 m3/(h, m3 compost). However, increased aeration caused severe drying of
      the compost, but at one plant the addition of water was adequate to prevent
      drying. In conclusion, by increasing the aeration rates and adding water to
      compensate for drying, it was possible to shorten the time needed to produce a
      stable compost product and thus to increase the efficiency of the composting
      plants.

PMID- 17433656
TI  - Production and characterization of glazed tiles containing incinerated sewage
      sludge.
AB  - In this article, glaze with different colorants was applied to tile specimens
      manufactured by incinerated sewage sludge ash (ISSA) and clay. Improvements using
      different amounts of colorants, and glaze components and concentrations on tile
      bodies were investigated. Four different proportions of clay (by weight ratio)
      were replaced by ISSA. Tiles of size 12 cm x 6 cm x 1 cm were made and left in an
      electric furnace to make biscuit tiles at 800 degrees C. Afterwards, four
      colorants, Fe2O3 (red), V2O5 (yellow), CoCO3 (blue), and MnO2 (purple), and four
      different glaze concentrations were applied on biscuit tile specimens. These
      specimens were later sintered into glazed tiles at 1050 degrees C. The study
      shows that replacement of clay by sludge ash had adverse effects on properties of
      tiles. Water absorption increased and bending strength reduced with increased
      amounts of ash. However, both water absorption and bending strength improved for
      glazed ash tiles. Abrasion of grazed tiles reduced noticeably from 0.001 to 0.002
      g. This implies glaze can enhance abrasion resistance of tiles. Effects like
      lightfastness and acid-alkali resistance improved as different glazes were
      applied on tiles. In general, red glazed tiles showed the most stable
      performance, followed by blue, yellow, and purple.

PMID- 17433657
TI  - Paper waste - recycling, incineration or landfilling? A review of existing life
      cycle assessments.
AB  - A review of existing life cycle assessments (LCAs) on paper and cardboard waste
      has been undertaken. The objectives of the review were threefold. Firstly, to see
      whether a consistent message comes out of published LCA literature on optimum
      disposal or recycling solutions for this waste type. Such message has
      implications for current policy formulation on material recycling and disposal in
      the EU. Secondly, to identify key methodological issues of paper waste management
      LCAs, and enlighten the influence of such issues on the conclusions of the LCA
      studies. Thirdly, in light of the analysis made, to discuss whether it is at all
      valid to use the LCA methodology in its current development state to guide policy
      decisions on paper waste. A total of nine LCA studies containing altogether 73
      scenarios were selected from a thorough, international literature search. The
      selected studies are LCAs including comparisons of different management options
      for waste paper. Despite claims of inconsistency, the LCAs reviewed illustrate
      the environmental benefits in recycling over incineration or landfill options,
      for paper and cardboard waste. This broad consensus was found despite differences
      in geographic location and definitions of the paper recycling/disposal systems
      studied. A systematic exploration of the LCA studies showed, however, important
      methodological pitfalls and sources of error, mainly concerning differences in
      the definition of the system boundaries. Fifteen key assumptions were identified
      that cover the three paper cycle system areas: raw materials and forestry, paper
      production, and disposal/recovery. It was found that the outcome of the
      individual LCA studies largely depended on the choices made in some of these
      assumptions, most specifically the ones concerning energy use and generation, and
      forestry.

PMID- 17433658
TI  - Time series analysis of the effects of refuse collection on recycling: Taiwan's
      "Keep Trash Off the Ground" measure.
AB  - The state of recycling in Taiwan has seen significant achievements due to various
      recycling policies implemented by environmental agencies in recent years. These
      policies include the "Keep Trash Off the Ground" (KTOG) measure, the "Four-in-One
      Recycling Plan", the per-bag trash collection fee and mandatory garbage sorting.
      An important question worthy of study is which of these policies has had a more
      pervasive and critical impact on the outcome of recycling. For example, there is
      evidence that the KTOG measure made it more convenient for people to begin
      recycling. This study therefore first analyzed the monthly data over the past
      decade on the amounts of recyclables in Taiwan's three major cities. By examining
      time series plots and employing an analysis of the time series intervention
      model, we can better understand the extent of the effects of the KTOG measure on
      these cities' amounts of recyclables. The same effects were also analyzed for the
      mandatory garbage sorting policy and the per-bag trash collection fee. Results
      show that the KTOG measure, essentially a change in refuse collection practice,
      presented consistent and significant effects on these cities' amounts of
      recyclables. It is suggested that the key to improving participation in a
      recycling program in waste management is for techniques to be tailored to actual
      settings in a way that facilitates citizen cooperation.

PMID- 17433659
TI  - Agrochemical characterisation of the solid by-products and residues from the
      winery and distillery industry.
AB  - The winery and distillery industry produces a great quantity of residues, whose
      management and disposal are environmental problems due to their seasonal
      character and some polluting characteristics. The main solid by-products and
      residues generated are grape stalk, grape pomace or marc, wine lee, exhausted
      grape marc and winery sludge. In this study, 87 samples of winery and distillery
      residues were collected from different Spanish wineries and distilleries.
      Electrical conductivity, pH, total organic matter, organic carbon, polyphenols
      and contents of plant nutrients and heavy metals were determined. The purpose of
      this research was to study the composition of these wastes and to find
      relationships in order to use easily analysable parameters to estimate their
      composition. In general, the winery and distillery residues showed low pH (mean
      values ranged from 3.8 to 6.8) and electrical conductivity values (1.62-6.15 dS
      m(-1)) and high organic matter (669-920 g kg(-1)) and macronutrient contents,
      especially in K (11.9-72.8 g kg(-1)). However, a notable polyphenol concentration
      (1.2-19.0 g kg(-1)) and low micronutrient and heavy metal contents were also
      observed, some of these properties being incompatible with agricultural
      requirements. Therefore, conditioning treatments are necessary prior to possible
      use of these wastes. In all wastes, significant correlations were found between
      easily determined parameters, such as pH, electrical conductivity and total
      organic matter, and most of the parameters studied. The regression models
      obtained are also discussed.

PMID- 17433660
TI  - Landfill modelling in LCA - a contribution based on empirical data.
AB  - Landfills at various stages of development, depending on their age and location,
      can be found throughout Europe. The type of facilities goes from uncontrolled
      dumpsites to highly engineered facilities with leachate and gas management. In
      addition, some landfills are designed to receive untreated waste, while others
      can receive incineration residues (MSWI) or residues after mechanical biological
      treatment (MBT). Dimension, type and duration of the emissions from landfills
      depend on the quality of the disposed waste, the technical design, and the
      location of the landfill. Environmental impacts are produced by the leachate
      (heavy metals, organic loading), emissions into the air (CH(4), hydrocarbons,
      halogenated hydrocarbons) and from the energy or fuel requirements for the
      operation of the landfill (SO(2) and NO(x) from the production of electricity
      from fossil fuels). To include landfilling in an life-cycle assessment (LCA)
      approach entails several methodological questions (multi-input process, site
      specific influence, time dependency). Additionally, no experiences are available
      with regard to mid-term behaviour (decades) for the relatively new types of
      landfill (MBT landfill, landfill for residues from MSWI). The present paper
      focuses on two main issues concerning modelling of landfills in LCA: Firstly, it
      is an acknowledged fact that emissions from landfills may prevail for a very long
      time, often thousands of years or longer. The choice of time frame in the LCA of
      landfilling may therefore clearly affect the results. Secondly, the reliability
      of results obtained through a life-cycle assessment depends on the availability
      and quality of Life Cycle Inventory (LCI) data. Therefore the choice of the
      general approach, using multi-input inventory tool versus empirical results, may
      also influence the results. In this paper the different approaches concerning
      time horizon and LCI will be introduced and discussed. In the application of
      empirical results, the presence of data gaps may limit the inclusion of several
      impact categories and therefore affect the results obtained by the study. For
      this reason, every effort has been made to provide high-quality empirical LCI
      data for landfills in Central Europe.

PMID- 17433661
TI  - Life cycle thinking in waste management: summary of European Commission's Malta
      2005 workshop and pilot studies.
AB  - Life cycle thinking is essential to consider the implications of different waste
      management systems beyond their traditional regional boundaries. Building on data
      provided by representatives of Bulgaria, Cyprus, Czech Republic, Hungary,
      Lithuania, Malta, Poland, Romania, and Slovakia, the European Commission's DG JRC
      conducted a series of life cycle pilot studies in the context of municipal waste
      management. The results were presented in a JRC workshop in Malta, where the
      government representatives also outlined their national strategies focusing on
      the main related achievements. Proposed follow-up activities include a close
      interaction with the Commission's project, the European Platform on Life Cycle
      Assessment, to develop straightforward European life cycle guidelines for the
      management of various wastes.

PMID- 17433662
TI  - Non-parametric analysis of infrared spectra for recognition of glass and glass
      ceramic fragments in recycling plants.
AB  - Glass ceramic detection in glass recycling plants represents a still unsolved
      problem, as glass ceramic material looks like normal glass and is usually
      detected only by specialized personnel. The presence of glass-like contaminants
      inside waste glass products, resulting from both industrial and differentiated
      urban waste collection, increases process production costs and reduces final
      product quality. In this paper an innovative approach for glass ceramic
      recognition, based on the non-parametric analysis of infrared spectra, is
      proposed and investigated. The work was specifically addressed to the spectral
      classification of glass and glass ceramic fragments collected in an actual
      recycling plant from three different production lines: flat glass, colored
      container-glass and white container-glass. The analyses, carried out in the near
      and mid-infrared (NIR-MIR) spectral field (1280-4480 nm), show that glass ceramic
      and glass fragments can be recognized by applying a wavelet transform, with a
      small classification error. Moreover, a method for selecting only a small subset
      of relevant wavelength ratios is suggested, allowing the conduct of a fast
      recognition of the two classes of materials. The results show how the proposed
      approach can be utilized to develop a classification engine to be integrated
      inside a hardware and software sorting architecture for fast "on-line" ceramic
      glass recognition and separation.

PMID- 17433663
TI  - Application of the US decision support tool for materials and waste management.
AB  - The US Environmental Protection Agency (US EPA) launched the Resource
      Conservation Challenge (RCC) in 2002 to help reduce waste and move towards more
      sustainable resource consumption. The objective of the RCC is to help
      communities, industries, and the public think in terms of materials management
      rather than waste disposal. Reducing cost, finding more efficient and effective
      strategies to manage municipal waste, and thinking in terms of materials
      management requires a holistic approach that considers life-cycle environmental
      tradeoffs. The US EPA's National Risk Management Research Laboratory has led the
      development of a municipal solid waste decision support tool (MSW-DST). The
      computer software can be used to calculate life-cycle environmental tradeoffs and
      full costs of different waste management or materials recovery programs. The
      environmental methodology is based on the use of life-cycle assessment and the
      cost methodology is based on the use of full-cost accounting. Life-cycle
      inventory (LCI) environmental impacts and costs are calculated from the point of
      collection, handling, transport, treatment, and disposal. For any materials that
      are recovered for recycling, offsets are calculated to reflect potential
      emissions savings from use of virgin materials. The use of the MSW-DST provides a
      standardized format and consistent basis to compare alternatives. This paper
      provides an illustration of how the MSW-DST can be used by evaluating ten
      management strategies for a hypothetical medium-sized community to compare the
      life-cycle environmental and cost tradeoffs. The LCI results from the MSW-DST are
      then used as inputs into another US EPA tool, the Tool for the reduction and
      assessment of chemical and other environmental impacts, to convert the LCI
      results into impact indicators. The goal of this paper is to demonstrate how the
      MSW-DST can be used to identify and balance multiple criteria (costs and
      environmental impacts) when evaluating options for materials and waste
      management. This type of approach is needed in identifying strategies that lead
      to reduced waste and more sustainable resource consumption. This helps to meet
      the goals established in the US EPA's Resource Conservation Challenge.

PMID- 17433664
TI  - Municipal solid waste management in Indian cities - A review.
AB  - Municipal solid waste management (MSWM) is one of the major environmental
      problems of Indian cities. Improper management of municipal solid waste (MSW)
      causes hazards to inhabitants. Various studies reveal that about 90% of MSW is
      disposed of unscientifically in open dumps and landfills, creating problems to
      public health and the environment. In the present study, an attempt has been made
      to provide a comprehensive review of the characteristics, generation, collection
      and transportation, disposal and treatment technologies of MSW practiced in
      India. The study pertaining to MSWM for Indian cities has been carried out to
      evaluate the current status and identify the major problems. Various adopted
      treatment technologies for MSW are critically reviewed, along with their
      advantages and limitations. The study is concluded with a few fruitful
      suggestions, which may be beneficial to encourage the competent
      authorities/researchers to work towards further improvement of the present
      system.

PMID- 17433665
TI  - Piezoelectric urea biosensor based on immobilization of urease onto nanoporous
      alumina membranes.
AB  - The urease was immobilized onto nanoporous alumina membranes prepared by the two
      step anodization method, and a novel piezoelectric urea sensing system with
      separated porous alumina/urease electrode has been developed through measuring
      the conductivity change of immobilized urease/urea reaction. The process of
      urease immobilization was optimized and the performance of the developed urea
      biosensor was evaluated. The obtained urea biosensor presented high-selectivity
      monitoring of urea, better reproducibility (S.D.=0.02, n=6), shorter response
      time (30s), wider linear range (0.5 microM to 3mM), lower detection limit (0.2
      microM) and good long-term storage stability (with about 76% of the enzymatic
      activity retained after 30 days). The clinical analysis of the urea biosensor
      confirmed the feasibility of urea detection in urine samples.

PMID- 17433666
TI  - Primary central nervous system lymphoma: biological aspects and controversies in
      management.
AB  - INTRODUCTION: This review was produced from the workshop on primary central
      nervous system lymphoma (PCNSL) at the European Cancer Conference (ECCO 13) in
      Paris in 2005. It covers the presentation and biological features of the disease
      (Professor Khe Hoang-Xuan). The role of chemotherapy, including the management of
      intraocular lymphoma and the use of high dose chemotherapy followed by autologous
      stem cell transplantation for PCNSL, is discussed (Dr. Andres Ferreri) as well as
      controversies in the use of whole brain radiotherapy (WBRT) after chemotherapy
      (Dr. Michele Reni). The topics covered with discussants at the workshop are also
      summarised. CONCLUSION: The imaging of the brain and the histopathology including
      detailed immunohistochemistry is of vital importance in making an accurate
      diagnosis of the disease and understanding the extent of spread of the disease in
      the CNS. The importance of high dose methotrexate (HDMTX; dose > or = 1g/m(2)),
      as the most active drug in the treatment of PCNSL, is stressed. The authors
      recommend that HDMTX alone or in combination with other active chemotherapy
      agents should be used to treat PCNSL followed by whole brain radiotherapy (WBRT)
      unless contraindicated because of the advanced age of the patient and existing
      cognitive impairment. Only published protocols should be used unless the patient
      is to be offered a trial that has either national or international support.
      Baseline neuropsychological tests should be carried out before treatment and
      repeated during and after treatment. The risks of cognitive impairment associated
      with the disease, with methotrexate - containing chemotherapy and with whole
      brain radiotherapy should be explained to patients and relatives when obtaining
      informed consent. Long-term survival, with current treatment regimes, is possible
      with PCNSL but this appears limited to patients less than 60 years of age at
      presentation (mostly patients less than 50 years of age).

PMID- 17433667
TI  - Larvicidal activity of saponins from Balanites aegyptiaca callus against Aedes
      aegypti mosquito.
AB  - Seeking an alternative approach for producing a larvicidal product from Balanites
      aegyptiaca plants, callus was produced from in vitro cultures of root explants
      and its larvicidal activity against Aedes aegypti mosquito larvae was evaluated.
      Concentrations of 0, 50, 100, 500, 1000, and 1500 ppm of saponins from the root
      derived callus of B. aegyptiaca were used to determine larvicidal effects and
      consequent effect on adult emergence. A dose-dependent effect was observed. In a
      chronic mortality assessment (after 7 days of exposure), concentrations of 500
      ppm or greater killed 100% of the test larvae population. Fifty parts per million
      showed no difference in larval mortality compared to the control (0 ppm);
      however, this concentration allowed one-fourth of the adult emergence of the
      control treatment. These results suggest that saponins from in vitro cultures of
      the root explant of B. aegyptiaca can be used as a larvicidal agent against A.
      aegypti larvae.

PMID- 17433668
TI  - Co-composting of oil exhausted olive-cake, poultry manure and industrial residues
      of agro-food activity for soil amendment.
AB  - The co-composting of exhausted olive-cake with poultry manure and sesame shells
      was investigated. These organic solid wastes were watered by the confectionary
      wastewater which is characterized by its high content of residual sugars raising
      its COD. Four aerated windrows were performed to establish the effects of
      confectionary by-products on the compost process. Different mixtures of the agro
      industrial wastes were used. During the composting process, physico-chemical
      parameters (temperature, moisture, pH, electrical conductivity, total carbon and
      total nitrogen) were studied. The stability of the biological system was noticed
      after 70 days. The final products were characterized by their relatively high
      organic matter content, and low C/N ratio of 14-17. The humidification of the
      windrows with the wastewater seemed to have accelerated the composting process in
      comparison to a windrow humidified with water. In addition, the organic matter
      degradation was enhanced to reach 55-70%. The application of the obtained
      composts to soil appeared to significantly improve the soil fertility. Indeed,
      field experiments showed an increase in potato yield; the production was 30.5
      37.5 tons ha(-1), compared to 30.5 tons ha(-1) with farm manure.

PMID- 17433669
TI  - Studies on cottonseed oil biodiesel prepared in non-catalytic SCF conditions.
AB  - The vegetable oils are all extremely viscous with viscosities ranging from 10 to
      20 times greater than petroleum diesel fuel. The purpose of the
      transesterification process is to lower the viscosity of the oil. Methyl and
      ethyl esters as biodiesel were prepared from cottonseed oil through
      transesterification using non-catalytic supercritical fluids. The
      transesterfication of linseed oil in SCF such as methanol and ethanol has proved
      to be the most promising process. The biodiesels were characterized for their
      physical and main fuel properties including viscosity, density, flash point and
      higher heating value (HHV). The viscosities of biodiesels (3.6-4.0 mm(2)/s at 311
      K) were much less than those of pure oils (33-36 mm(2)/s at 311 K), and their
      HHVs of approximately 40.5 MJ/kg were 10% less than those of petrodiesel fuels
      (approximately 45 MJ/kg). The flash point values (435-445 K) of methyl and ethyl
      esters are highly lower than that of cottonseed oil (507-512 K). The most
      important variables affecting the ester yield during the transesterification
      reaction are molar ratio of alcohol to vegetable oil and reaction temperature.

PMID- 17433670
TI  - Discovery of novel indazole-linked triazoles as antifungal agents.
AB  - The in vitro and in vivo activities of a series of (2R,3R)-2-(2,4-difluorophenyl)
      3-(substituted indazol-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol as potential
      antifungal agents are described. In particular, the analog 12j having 5-bromo
      substitution on the indazole ring exhibited significant antifungal activity
      against a variety of fungal cultures (Candida spp. and Aspergillus spp.). In
      addition, oral administration of 12j showed its excellent efficacy against
      Candida albicans in a murine infection model and the significantly improved
      survival rates of the infected mice.

PMID- 17433671
TI  - Annonaceous acetogenin mimics bearing a terminal lactam and their cytotoxicity
      against cancer cells.
AB  - Annonaceous acetogenins are a large class of naturally occurring polyketides
      exhibiting potent anticancer activities. Based on our previous discovery of
      AA005, a multi-ether mimic of natural acetogenins having potent antitumor
      activities and significant selectivity between normal cells and cancer cells, a
      new series of mimics containing a terminal lactam were designed, synthesized and
      evaluated. Bioactivity study against cancer cells shows that the N-methylated
      lactam-containing compounds 3, 4, and 5 exhibit comparable potencies to that of
      AA005, as well as the similar selectivity to cancer cells. Hydrocarbon-length
      effects of N-alkyl were further explored through synthesizing derivatives 24-26,
      and application of this derivation protocol to the fluorescent labeling was also
      investigated.

PMID- 17433672
TI  - Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4
      inhibitor by application of molecular modeling and X-ray crystallography of
      sitagliptin.
AB  - Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray
      crystal structure of sitagliptin bound to DPP-4 suggested that the central beta
      amino butyl amide moiety could be replaced with a cyclohexylamine group. This was
      confirmed by structural analysis and the resulting analog 2a was synthesized and
      found to be a potent DPP-4 inhibitor (IC(50)=21 nM) with excellent in vivo
      activity and pharmacokinetic profile.

PMID- 17433673
TI  - Novel 3-galloylamido-N'-substituted-2,6-piperidinedione-N-acetamide
      peptidomimetics as metalloproteinase inhibitors.
AB  - Both of aminopeptidase N (APN) and matrix metalloproteinase (MMP) are essential
      metallopeptidases in the development of tumor invasion and angiogenesis. Novel
      potent peptidomimetic inhibitors, containing 3-galloylamido-N'-substituted-2,6
      piperidinedione-N-acetamide, have been designed and synthesized according to the
      conformational constraint strategy. The preliminary biological test showed that
      most of the compounds displayed high inhibitory activity against MMP-2 and low
      activity against APN except compounds 6 (IC(50)=3.1microM) and 4l
      (IC(50)=5.2microM) which exhibit similar potency to Bestatin (IC(50)=2.4microM).

PMID- 17433674
TI  - Syntheses and antibacterial activity of phendioxy substituted cyclic enediynes.
AB  - Syntheses and antibacterial activity of 13-membered 1,3-phendioxy substituted
      cyclic enediynes are reported. The compounds were screened against gram-positive
      and gram-negative strains and some of the compounds exhibit potent antibacterial
      activity.

PMID- 17433676
TI  - 145th ENMC International Workshop: planning for an International Trial of Steroid
      Dosage Regimes in DMD (FOR DMD), 22-24th October 2006, Naarden, The Netherlands.

PMID- 17433675
TI  - ACTIVLIM: a Rasch-built measure of activity limitations in children and adults
      with neuromuscular disorders.
AB  - A common measure of activity limitations for both children and adults with
      neuromuscular disorders was developed using the Rasch model. A self-reported
      questionnaire containing daily activities was submitted to 245 adult patients and
      to the parents of 124 affected children from the two major Belgian communities.
      They were asked to provide their perceived difficulty in performing daily
      activities on a three-level scale. The 22 items of the final scale define a
      unidimensional and linear measure of activity limitations and show a continuous
      progression in their difficulty. The item difficulty hierarchy is invariant with
      regard to the diagnosis, community, gender and age. The scale exhibits a good
      precision, since the 22 items are well targeted on our sample (r=0.96);
      furthermore, it is reproducible over time (ICC=0.93). The patients' measures are
      related to the Functional Independence Measure motor score (rho=0.85), to the
      Brooke (rho=-0.63) grade and to the Vignos (rho=-0.83) grade.

PMID- 17433677
TI  - The Hammersmith functional score correlates with the SMN2 copy number: a
      multicentric study.
AB  - Previous studies showed that SMN2 copy number correlates inversely with the
      disease severity. Our aim was to evaluate SMN2 copy numbers and the Hammersmith
      functional motor scale in 87 patients with SMA II in order to establish whether,
      within SMAII, the number of copies correlates with the severity of functional
      impairment. Our results showed a relative variability of functional scores, but a
      significant correlation between the number of SMN2 genes and the level of
      function.

PMID- 17433678
TI  - GDAP1 mutations in Czech families with early-onset CMT.
AB  - Mutations in the ganglioside-induced differentiation associated protein-1 gene
      (GDAP1) cause autosomal recessive (AR) demyelinating or axonal Charcot-Marie
      Tooth neuropathy (CMT). In order to establish the spectrum and frequency of GDAP1
      mutations in Czech population, we sequenced GDAP1 in 74 Czech patients from 69
      unrelated families with early-onset demyelinating or axonal CMT compatible with
      AR inheritance. We identified three isolated patients with GDAP1 mutations in
      both alleles. In one additional sporadic and one familial case, the second
      pathogenic mutation remained unknown. Overall, we detected two different
      mutations, a novel R191X nonsense and a L239F missense mutation. L239F previously
      described in a German-Italian family is a prevalent mutation in Czech population
      and we give evidence for its common ancestral origin. All Czech GDAP1 patients
      developed involvement of all four limbs evident by the end of second decade,
      except for one isolated patient showing very slow disease progression. All
      patients displayed axonal type of neuropathy.

PMID- 17433679
TI  - 3rd UK Spinal Muscular Atrophy (SMA) Researchers Network Meeting.

PMID- 17433680
TI  - Cognitive profile in childhood myotonic dystrophy type 1: is there a global
      impairment?
AB  - The objective of this study was to assess the cognitive profile in the childhood
      onset form of myotonic dystrophy (DM1). We carried out a general cognitive
      abilities study on 36 patients (6-18 years). Results of Full Scale IQ , VIQ
      (Verbal IQ) and PIQ (Performance IQ) measures are discussed in terms of global
      cognitive impairment depending on the (CTG)n repeat size and the transmitting
      parent's sex. The results highlighted a negative correlation between the CTG
      repeat size and cognitive function: (1) 55% of the subjects (20/34) presented
      large CTG expansion (mean=761) correlated with significant extensive cognitive
      deficits (mean Full Scale IQ=56) in both intelligence scales (verbal and non
      verbal); most of them exhibited DM1 maternal transmission. (2) In the case of
      smaller expansion (mean=527), 38% of the subjects exhibited a subnormal
      intelligence (mean Full Scale IQ=86) but performed poorly on subtests evaluating
      attention/memory function and presented a severe deficit in visuospatial and/or
      visuo-constructive skills. Most of these children had paternal transmission but a
      few had an affected mother.

PMID- 17433681
TI  - Role of pre-surgical breast MRI in the management of invasive breast carcinoma.
AB  - The purpose of the study was to assess the role of preoperative breast magnetic
      resonance imaging (MRI) as a complementary tool to routine imaging methods in the
      management of women affected by invasive breast carcinoma. Mammograms, sonograms
      and biopsy results of 121 breasts in 118 women affected by invasive breast
      carcinoma, who underwent pre-surgical breast MR, were re-examined to identify
      patients theoretically eligible for conservative surgery instead of radical
      mastectomy. Surgery effectively performed was evaluated to identify cases for
      which MRI determined a change in management. The gold standard was the final
      pathology. Breast MRI determined an overall change in management in 22 out of 121
      breasts (18.2%), and in two out of 87 breasts (25.3%) in patients eligible for
      conservative surgery. In the evaluation of single breasts, MRI resulted in true
      positive in 22 out of 29 breasts (75.9%), false-positive in 7 out of 29 breasts
      (24.1%), leading to over-treatment in women whose treatment was changed from
      conservative surgery to radical mastectomy. MRI sensitivity in the detection of
      additional foci not seen on conventional imaging was 57.4%, overall sensitivity
      87.4%, sensitivity for invasive cancers 93.1%, while for ductal carcinoma in situ
      it was 58.8%. In conclusion, breast MRI determines a significant change in the
      management of patients affected by invasive breast carcinoma, particularly in
      patients eligible for conservative surgery after standard breast examination.

PMID- 17433682
TI  - A novel microtubule-depolymerizing kinesin involved in length control of a
      eukaryotic flagellum.
AB  - Cilia and flagella are complex, microtubule (MT)-filled cell organelles of which
      the structure is evolutionarily conserved from protistan cells to mammalian sperm
      and the size is regulated. The best-established model for flagellar length (FL)
      control is set by the balance of continuous MT assembly and disassembly occurring
      at the flagellar tip. Because steady-state assembly of tubulin onto the distal
      end of the flagellum requires intraflagellar transport (IFT)--a bidirectional
      movement of large protein complexes that occurs within the flagellum--FL control
      must rely upon the regulation of IFT. This does not preclude that other pathways
      might "directly" affect MT assembly and disassembly. Now, among the superfamily
      of kinesins, family-13 (MCAK/KIF2) members exhibit a MT-depolymerizing activity
      responsible for their essential functions in mitosis. Here we present a novel
      family-13 kinesin from the flagellated protozoan parasite Leishmania major, that
      localizes essentially to the flagellum, and whose overexpression produces
      flagellar shortening and knockdown yields long flagella. Using negative mutants,
      we demonstrate that this phenotype is linked with the MT-binding and 
      depolymerizing activity of this kinesin. This is the first report of an effector
      protein involved in FL control through a direct action in MT dynamics, thus this
      finding complements the assembly-disassembly model.

PMID- 17433683
TI  - Birdsong memory: a neural dissociation between song recognition and production.
AB  - Songbirds learn their song from an adult conspecific tutor when they are young,
      much like the acquisition of speech in human infants. When an adult zebra finch
      is re-exposed to its tutor's song, there is increased neuronal activation in the
      caudomedial nidopallium (NCM), the songbird equivalent of the auditory
      association cortex. This neuronal activation is related to the fidelity of song
      imitation, suggesting that the NCM may contain the neural representation of song
      memory. We found that bilateral neurotoxic lesions to the NCM of adult male zebra
      finches impaired tutor-song recognition but did not affect the males' song
      production or their ability to discriminate calls. These findings demonstrate
      that the NCM performs an essential role in the representation of tutor-song
      memory. In addition, our results show that tutor-song memory and a motor program
      for the bird's own song have separate neural representations in the songbird
      brain. Thus, in both humans and songbirds, the cognitive systems of vocal
      production and auditory recognition memory are subserved by distinct brain
      regions.

PMID- 17433685
TI  - A body-fixed-sensor based analysis of compensatory trunk movements during
      unconstrained walking.
AB  - This paper presents a body-fixed-sensor (BFS) based approach for quantifying
      compensatory trunk movements during unconstrained walking. Orientation of trunk
      segments was calculated by fusing low-pass filtered accelerometer data and high
      pass filtered data from gyroscopes. To evaluate accuracy, frontal plane angular
      movements of the pelvis during different treadmill walking conditions were
      compared to results based on a high-accuracy camera system. Mean differences
      between the two methods remained within 0.31 degrees , standard deviations of
      differences within 1.4 degrees and error percentages within 17.7%. Correlations
      ranged from 0.87 to 0.99. To test whether the method could discriminate between
      hip arthroplasty patients with and without compensatory trunk movements, the BFS
      based method was applied to patients and healthy controls during overground
      walking. Within a walking speed range of 0.40-1.10 m/s, the peak-to-peak
      amplitudes of trunk movements ranged from 5.7 degrees to 7.9 degrees in healthy
      subjects and from 13.5 degrees to 26.3 degrees versus 7.4 degrees to 13.8 degrees
      in patients with and without compensatory trunk movements, respectively. The
      presented BFS based approach can be used to assess spatio-temporal gait
      parameters and trunk movements and thus to objectively monitor gait function in
      hip arthroplasty patients in a clinical setting.

PMID- 17433686
TI  - New aspects of natural products in drug discovery.
AB  - During the past 15 years, most large pharmaceutical companies have decreased the
      screening of natural products for drug discovery in favor of synthetic compound
      libraries. Main reasons for this include the incompatibility of natural product
      libraries with high-throughput screening and the marginal improvement in core
      technologies for natural product screening in the late 1980s and early 1990 s.
      Recently, the development of new technologies has revolutionized the screening of
      natural products. Applying these technologies compensates for the inherent
      limitations of natural products and offers a unique opportunity to re-establish
      natural products as a major source for drug discovery. Examples of these new
      advances and technologies are described in this review.

PMID- 17433688
TI  - 'Talk and die' patients presenting to a major trauma centre over a 10 year
      period: a critical review.
AB  - 'Talk and die patients' describes a small number of patients who present with a
      mild head injury (Glasgow Coma Scale [GCS] 13-15) and then subsequently
      deteriorate and die from intracranial causes. We analysed the medical records of
      all those adult patients whose primary diagnosis as the cause of death was head
      injury, as determined by the coroner, who were admitted to a major Australian
      trauma centre between January 1994 and December 2003 (a 10-year period). The
      clinical profile of those patients who fulfilled the criteria of 'talk and die'
      were documented, including age, mode of injury, initial GCS, lucid interval, CT
      scan reports, operation performed, post mortem findings and intracranial cause of
      death. Factors considered potentially contributory to the patients'
      deterioration, such as delays in CT scanning or patient transfer, coagulopathy or
      hypoxic episodes were also noted. The incidence of 'talk and die' patients was
      2.6% (15 out of 569) overall and the annual incidence did not significantly alter
      over the 10-year period of the study. The small number of patients precludes
      inferences regarding causal relationships, although potentially preventable
      factors, which could have been contributory to patient deterioration, were
      identified.

PMID- 17433689
TI  - Intraventricular rhabdoid meningioma.
AB  - Rhabdoid meningioma is a rare variant of meningioma, often found in tumour
      recurrences. We report a 55-year-old woman with a history of intraventricular
      fibroblastic meningioma, who developed headache and tinnitus 5 years after
      complete resection of the initial tumour. Imaging confirmed a recurrent tumour in
      the intraventricular location. Histological analysis revealed rhabdoid
      meningioma. We reviewed the literature and were unable to find any previously
      reported cases of intraventricular rhabdoid meningioma.

PMID- 17433690
TI  - Spinal subdural abscess: a rare cause of low back pain.
AB  - Spinal subdural abscess (SSA) is a rare but well-described entity. It may occur
      secondary to a systemic infectious focus or following a surgical procedure. There
      are only two SSA cases in the literature that are unrelated to such conditions
      and without any well-documented etiology. SSA is a neurosurgical emergency and
      diagnosis may be difficult. Progressive neurological deficits and severe pain
      with fever suggest the diagnosis. Surgical drainage and subsequent prompt
      antimicrobial therapy should be performed without delay. We report a patient with
      SSA unrelated to any predisposing condition and discuss underlying mechanisms of
      this disease.

PMID- 17433691
TI  - The prothrombin gene G20210A variant and puerperal cerebral venous and sinus
      thrombosis in South Indian women.
AB  - Pregnancy and puerperium raise the risk of thrombotic events, and these risks are
      likely to be increased in women who are carriers of thrombophilic gene
      polymorphisms. Prothrombin G20210A variant is reported to be the second most
      frequent prothrombotic polymorphism in Caucasians. Our aim was to determine the
      prevalence of this variant in south Indian women and examine its association with
      cerebral venous and sinus thrombosis occurring during puerperium. We investigated
      96 women with puerperal cerebral veno-sinus thrombosis (CVT) and 103 age-matched
      women with no post-partum complications. We used restriction fragment length
      polymorphism analysis to identify their genotypes. The prothrombin G20210A
      variant was not detected in either the CVT patients or the healthy control
      subjects. Our study on a large series of patients with puerperal CVT shows that
      the prothrombin G20210A variant is not present in south Indian women and is not
      associated with puerperal CVT. This study also highlights the fact that there are
      racial differences in the risk factors for thrombosis, which should be considered
      when investigating these patients.

PMID- 17433694
TI  - Modified pre-curved patellar basket plate, reconstruction of the proper length
      and position of the patellar ligament--a biomechanical analysis.
AB  - Biomechanical properties of basket plate fixation for fracture dislocation in the
      distal part of the patella were studied on 22 fresh-frozen lower extremities
      (human cadaveric knees). The patella and the patellar ligament with the proximal
      tibia were removed. A comminuted fracture of the distal part of the patella was
      created with a chisel. The fractured patella, patellar ligament and tibial
      tuberosity of each specimen were fixed with a basket plate and mounted into the
      jaws of the testing machine. The measured load to failure was 421.66+/-45.90 N,
      which is approximately 70% higher than the results in other studies. The results
      of the measurements verified the results of finite element analysis. The modified
      precurved patellar basket plate developed in this study showed improved
      performance compared to the pre-existing fixation methods.

PMID- 17433695
TI  - In-vitro investigation of oxazol and urea analogues of morphinan at opioid
      receptors.
AB  - A series of 2-amino-oxazole (7 and 8) analogs and 2-one-oxazole analogs (9 and
      10) were synthesized from cyclorphan (1) or butorphan (2) and evaluated in-vitro
      by their binding affinity at mu, delta, and kappa opioid receptors and compared
      with their 2-aminothiozole analogs 5 and 6. Ligands 7-10 showed decreased
      affinities at kappa and mu receptors. Urea analogs (11-14) were also prepared
      from 2-aminocyclorphan (3) or 2-aminobutorphan (4) and evaluated in-vitro by
      their binding affinity at mu, delta, and kappa opioid receptors. The urea derived
      opioids retained their affinities at mu receptors while showing increased
      affinities at delta receptors and decreased affinities at kappa receptors.
      Functional activities of these compounds were measured in the [35S]GTPgammaS
      binding assay, illustrating that all of these ligands were kappa agonists. At the
      mu receptor, compounds 11 and 12 were mu agonist/antagonists.

PMID- 17433693
TI  - Bacterial response regulators: versatile regulatory strategies from common
      domains.
AB  - Response regulators (RRs) comprise a major family of signaling proteins in
      prokaryotes. A modular architecture that consists of a conserved receiver domain
      and a variable effector domain enables RRs to function as phosphorylation
      regulated switches that couple a wide variety of cellular behaviors to
      environmental cues. Recently, advances have been made in understanding RR
      functions both at genome-wide and molecular levels. Global techniques have been
      developed to analyze RR input and output, expanding the scope of characterization
      of these versatile components. Meanwhile, structural studies have revealed that,
      despite common structures and mechanisms of function within individual domains, a
      range of interactions between receiver and effector domains confer great
      diversity in regulatory strategies, optimizing individual RRs for the specific
      regulatory needs of different signaling systems.

PMID- 17433696
TI  - Scaffold hopping, synthesis and structure-activity relationships of 5,6-diaryl
      pyrazine-2-amide derivatives: a novel series of CB1 receptor antagonists.
AB  - A scaffold hopping approach has been exploited to design a novel class of
      cannabinoid (CB1) receptor antagonists for the treatment of obesity. On the basis
      of shape-complementarity and synthetic feasibility the central fragment, a
      methylpyrazole, in Rimonabant was replaced by a pyrazine. The synthesis and CB1
      antagonistic activities of a new series of 5,6-diaryl-pyrazine-2-amide
      derivatives are described. Several compounds showed antagonist potency below 10nM
      for the CB1 receptor.

PMID- 17433697
TI  - Binding of lectins to DNA micro-assemblies: modification of nucleo-cages with
      lactose-conjugated psoralen.
AB  - Spherical DNA micro-assemblies appended with lactose units (Lactose-nucleo-cages,
      Lac-NC) are newly developed. DNA spherical assemblies self-assembled from
      suitably designed three oligodeoxyribonucleotides (ODNs) 1-3 were cross-linked by
      lactose-conjugated psoralen derivative 4. Confocal laser scanning fluorescence
      microscopy (CLSM) observation of Lac-NC shows that rhodamine labeled peanut
      lectin (Rho-PNA: a galactose-specific lectin) binds to lactose-modified nucleo
      cages with higher affinity compared to that of unmodified nucleo-cages. Binding
      isotherm experiments indicated that the apparent affinity constant of Rho-PNA to
      Lac-NC was in the order of 10(5) M(-1).

PMID- 17433698
TI  - Synthesis and biological evaluation of phosphino dipeptide isostere inhibitor of
      human beta-secretase (BACE1).
AB  - Phosphino dipeptide (PDP) isosteres are known to be useful analogues of the
      transition state of metalloprotease substrates. Here we describe the use of this
      unit for the design of aspartic protease inhibitors. A PDP analogue of OM00-3, a
      potent BACE1 inhibitor, was synthesized and exhibited high biological activity
      (IC50 approximately 12 nM).

PMID- 17433699
TI  - Differential distribution of some extracellular matrix fibers in an
      experimentally denervated rat megaileum.
AB  - Absence of enteric neurons is associated with thickening of the intestinal
      muscularis externa in Chagas' disease. The thickening is due to hyperplasia and
      hypertrophy of the smooth muscle cells and increased extracellular matrix
      components. The influence of the nervous system on the structure of the smooth
      muscle cells and its associated matrix has been poorly investigated. An
      experimental model of denervation of the ileum in rats was performed by
      application of the surfactant agent benzalkonium chloride that selectively
      destroys the myenteric plexus. Three months later, ileal tissue samples were
      obtained and studied by histochemistry and transmission electron microsocopy.
      Sham operated rats were used as controls. The diameter of collagen fibrils was
      evaluated in electron micrographs. The histopathological analysis showed
      thickening of the muscular layer. The thin and weakly arranged collagen and
      reticulin fibers surrounding the smooth muscle cells, observed in control cases
      by Picrosirius polarization (PSP) stain method, corresponded to a population of
      loosely packed thin collagen fibrils of uniform diameters (mean=29.16 nm) at the
      ultrastructural level. In contrast, the thick and strongly birefringent fibers
      around the muscle cells, observed in the treated group, stained by PSP,
      corresponded to densely packed thicker fibrils with large variation in diameter
      (mean=39.41 nm). Comparison of the data demonstrated statistically significant
      difference between the groups suggesting that the replacement of loosely arranged
      reticulin fibers by fibrous tissue (with typical collagen fiber), may alter the
      biomechanical function resulting in impairment of muscular contraction.

PMID- 17433700
TI  - Testicular degeneration in Huntington disease.
AB  - Huntington disease (HD) is an adult onset, neurodegenerative disorder that
      results from CAG expansion in the HD gene. Recent work has demonstrated
      testicular degeneration in mouse models of HD and alterations in the hypothalamic
      pituitary-gonadal (HPG) axis in HD patients. Here, we show that HD patients have
      specific testicular pathology with reduced numbers of germ cells and abnormal
      seminiferous tubule morphology. In the YAC128 mouse model, testicular
      degeneration develops prior to 12 months of age, but at 12 months, there is no
      evidence for decreased testosterone levels or loss of GnRH neurons in the
      hypothalamus. This suggests that testicular pathology results from a direct toxic
      effect of mutant huntingtin in the testis and is supported by the fact that
      huntingtin is highly expressed in the affected cell populations in the testis.
      Understanding the pathogenesis of HD in the testis may reveal common critical
      pathways which lead to degeneration in both the brain and testis.

PMID- 17433701
TI  - Water deficit induces variation in expression of stress-responsive genes in two
      peanut (Arachis hypogaea L.) cultivars with different tolerance to drought.
AB  - Peanut (Arachis hypogaea L.) is an important subsistence and cash crop in the
      semi-arid tropics where it often suffers from drought stress. Although its
      ecophysiological responses are studied, little is known about the molecular
      events involved in its adaptive responses to drought. The aim of this study was
      to investigate the involvement of membrane phospholipid and protein degrading
      enzymes as well as protective proteins such as "late embryogenesis-abundant"
      (LEA) protein in peanut adaptive responses to drought. Partial cDNAs encoding
      putative phospholipase D alpha, cysteine protease, serine protease and a full
      length cDNA encoding a LEA protein were cloned. Their expression in response to
      progressive water deficit and rehydration was compared between cultivars
      differing in their tolerance to drought. Differential gene expression pattern
      according to either water deficit intensity and cultivar's tolerance to drought
      were observed. A good correspondence between the molecular responses of the
      studied cultivars and their physiological responses previously defined in
      greenhouse and field experiments was found. Molecular characters, as they were
      detectable at an early stage, could therefore be efficiently integrated in
      groundnut breeding programmes for drought adaptation. Thus, the relevance of the
      target genes as drought tolerance indicators is discussed.

PMID- 17433702
TI  - Biochemical characterization of a family of proteins that stabilizes a plant Ran
      protein in its GTP-bound conformation.
AB  - Ran-binding proteins (RanBP) are a group of proteins that bind to Ran (Ras
      related nuclear small G-protein) and thus control the GTP/GDP-bound states of the
      Ran and couple the Ran GTPase cycle to cellular processes. In an effort to
      identify potential downstream effectors for PsRan1-dependent cellular processes,
      we detected a group of pea Ran (PsRan1)-binding proteins and characterized their
      biochemical activities. A Ran overlay assay using [(32)P-GTP]-labeled PsRan1
      revealed three PsRan1-binding proteins (33, 45, and 85kDa in size) from total
      protein extracts of dark-grown pea plumules. These proteins bound preferentially
      to the Ran-GTP over Ran-GDP conformation and subsequently stabilized its GTP
      bound status. We propose that they are a family of proteins that maintain the Ran
      protein in the active conformation and are potential downstream mediators for
      PsRan1-dependent cellular processes. Our report provides the basis for
      characterizing and dissecting Ran downstream targets and Ran-mediated events, and
      it thus facilitates our understanding about the roles played by Ran/RanBP
      signaling pathways during plant growth and development.

PMID- 17433703
TI  - Giant vein graft aneurysm.

PMID- 17433704
TI  - New ultrasonic radiation reduces cerebral emboli during extracorporeal
      circulation.
AB  - OBJECTIVE: Cardiac surgery is associated with intraoperative cerebral emboli,
      which can result in postoperative neurological complications. A new ultrasonic
      transducer (EmBlocker) can be positioned on the ascending aorta and activation of
      the EmBlocker is expected to divert emboli to the descending aorta, thereby
      decreasing emboli in the cerebral arteries. In this preliminary animal study,
      safety and efficiency of this technology were examined. METHODS: In 14 pigs (+/
      70 kg), a median sternotomy was performed and the EmBlocker was positioned on the
      aorta ascendens at the level of the bifurcation of the aorta and the innominate
      artery. In one animal temperature measurements were performed. During these
      measurements, the EmBlocker was activated for four periods of 120 s of high power
      (1.5 W/cm(2)) and for four periods of 600 s of low power (0.5 W/cm(2)). In the
      safety study (n=6), the EmBlocker was activated twice the expected clinical
      duration (eight periods of 120 s of high power and, subsequently, one period of
      20 min of low power). Tissue samples (control and sonicated) were collected after
      1 week for histopathological evaluation (aorta, trachea, esophagus, vagus
      nerves). In the efficiency study (n=7), extracorporeal circulation was installed.
      Emboli (air and solid (1200, size 500 microm-750 microm)) were introduced in the
      proximal ascending aorta and the EmBlocker was alternately activated with high
      power for solid emboli injections and low power for air emboli injections.
      Transcranial Doppler (TCD) was used to analyse middle cerebral artery blood flow
      for occurrence of embolic signals, which were manually counted offline. RESULTS:
      Histopathology revealed no difference between control and sonicated tissue. There
      is a rise in temperature during EmBlocker activation, but in all measured tissues
      it was within limits; less then 42 degrees C for 2 min in the aorta wall directly
      under the EmBlocker. Use of the EmBlocker significantly reduced emboli in the
      cerebral arteries in an animal model; air emboli with 65% (left) and 69% (right)
      and solid emboli with 49% (left) and 50% (right). CONCLUSIONS: The new ultrasound
      technology can safely be applied and is capable of reducing emboli in the
      cerebral arteries during extracorporeal circulation. Use of the EmBlocker in
      cardiac surgery bears the potential to lower the risk of postoperative
      neurological complications. Clinical feasibility studies are in progress.

PMID- 17433705
TI  - Real-time detection of dental calculus by blue-LED-induced fluorescence
      spectroscopy.
AB  - Successful periodontal therapy requires sensitive techniques to discriminate
      dental calculus from healthy teeth. The aim of the present study was to develop a
      fluorescence-based procedure to enable real-time detection and quantification of
      dental calculus. Thirty human teeth--15 teeth with sub- and supragingival
      calculus and 15 healthy teeth--covered with a layer of physiological saline
      solution or blood were illuminated by a focused blue LED light source of 405 nm.
      Autofluorescence spectra recorded along a randomly selected line stretching over
      the crown-neck-root area of each tooth were utilized to evaluate a so called
      calculus parameter R, which was selected to define a relationship between the
      integrated intensities specific for healthy teeth and for calculus in the 477-497
      nm (S(A)) and 628-685 nm (S(B)) wavelength regions, respectively. Statistical
      analysis was performed and a cut-off threshold of R=0.2 was found to distinguish
      dental calculus from healthy teeth with 100% sensitivity and specificity under
      various experimental conditions. The results of the spectral evaluation were
      confirmed by clinical and histological findings. Automated real-time detection
      and diagnostics for clinical use were implemented by a corresponding software
      program written in Visual Basic language. The method enables cost-effective and
      reliable calculus detection, and can be further developed for imaging
      applications.

PMID- 17433706
TI  - Energy transfer to analyse membrane-integrated mitoxantrone in BCRP-overexpressed
      cells.
AB  - The binding and the diffusion of mitoxantrone (MTX) through the plasma membrane
      was performed by Forster resonance energy transfer (FRET) from the membrane
      fluorescent donor (4Di-10ASP) to the co-localized acceptor MTX. The MTX addition
      to living 4Di-10ASP-tagged cells resulted in the rapid quenching of the probe
      emission (1s), revealing the MTX binding to the outer leaflet. Then, a slower
      quenching (about 90s) occurred which corresponded to the MTX flip-flop into the
      inner leaflet. Changes of MTX integration into the plasma membrane were described
      in BCRP-overexpressed cells (HCT-116R) treated with (i) the BCRP inhibitor
      fumitremorgin C (FTC), (ii) cyclosporin A (CSA) and (iii) benzyl alcohol (BA).
      Treatments with FTC or CSA showed 80% and 40% higher flip-flop of MTX from the
      outer to the inner leaflet of HCT-116R cells. The addition of BA clearly
      increased the MTX integration into both outer and inner leaflets. Confocal
      fluorescence microscopy displayed that FTC, CSA and BA enhanced MTX accumulation
      in HCT-116R. In conclusion, Fumitremorgin C and agents modulating MTX
      accumulation resulted in higher MTX integration in the resistant cell membrane
      and could disrupt the membrane cohesion. This energy transfer method appears well
      adapted to describe the drug diffusion through the plasma membrane of living
      cells.

PMID- 17433707
TI  - Role of caveolins in body weight and insulin resistance regulation.
AB  - In spite of the growing understanding of the fundamental biology of energy
      homeostasis, it is evident that crucial pathways have yet to be identified.
      Caveolins, integral plasma membrane proteins present in caveolae with proven
      scaffolding, transport and signalling capabilities, have emerged as key players
      in shifting the focus of obesity and insulin resistance development to lipid
      dynamics and membrane microdomain disorders. Caveolin-1-knockout mice exhibit a
      lean phenotype with overt resistance to diet-induced obesity. Conversely,
      caveolin-3-knockout mice show marked insulin resistance together with increased
      body weight and adiposity despite normal food intake. Here, we discuss the
      participation of caveolins as novel modulators of adipocyte biology, highlight
      their role in insulin signalling and outline their potential relevance to human
      obesity development and treatment.

PMID- 17433708
TI  - C/EBPbeta serine 64, a phosphoacceptor site, has a critical role in LPS-induced
      IL-6 and MCP-1 transcription.
AB  - C/EBPbeta is a member of the CCAAT/enhancer binding protein family of
      transcription factors and has been shown to be a critical transcriptional
      regulator of various proinflammatory genes, including IL-6 and MCP-1. Serine 64
      in the transactivation domain of C/EBPbeta has recently been identified as a Ras
      induced phosphoacceptor site. The integrity of serine 64 along with threonine 189
      is important for the Ha-ras(V12)-induced transformation of NIH3T3 cells, however
      no target genes dependent upon serine 64 for their expression have been reported.
      In order to evaluate a potential role of serine 64 in C/EBPbeta-regulated
      cytokine expression, we expressed a form of C/EBPbeta with an alanine
      substitution at serine 64 (C/EBPbeta(S64A)) in P388 murine B lymphoblasts, which
      lack endogenous C/EBPbeta expression and are normally unresponsive to LPS for
      expression of IL-6 and MCP-1. In comparison to wild type C/EBPbeta, which
      robustly supports the LPS-induced expression of IL-6 and MCP-1, C/EBPbeta(S64A)
      was severely impaired in its ability to support the LPS-induced transcription of
      IL-6 and MCP-1. Furthermore, LPS stimulation increased the level of
      phosphorylation detected at serine 64. Thus, serine 64, probably through its
      phosphorylation, is a critical determinant of C/EBPbeta activity in the
      transcription of IL-6 and MCP-1.

PMID- 17433709
TI  - The effect of compound nutrients on stress-induced changes in serum IL-2, IL-6
      and TNF-alpha levels in rats.
AB  - The effect of compound nutrients on serum concentrations of the cytokines, such
      as interleukin (IL)-2, tumor necrosis factor-alpha (TNF-alpha) and interleukin
      (IL)-6 in immobilization and cold water-immersion stressed rat were investigated.
      Oral (gavage) administration of compound nutrients was found to attenuate the
      acute and chronic immobilization and cold water-immersion stress-induced increase
      in serum IL-6 level and decrease in IL-2 level. Compound nutrients exerted
      different effects on TNF-alpha level in two different models studied, with
      reduced serum TNF-alpha level in acute stress, while no significant effect in
      chronic stress. These results suggested that compound nutrients might be proposed
      as a possible candidate in the research or therapeutic modulation of stress
      related disorders.

PMID- 17433711
TI  - The E3 ubiquitin ligase Itch in T cell activation, differentiation, and
      tolerance.
AB  - Tagging a small molecule ubiquitin to a protein substrate, or protein
      ubiquitination, plays an important role in the immune responses. This process is
      catalyzed by a cascade of enzymatic reactions, with the E3 ubiquitin ligases
      being the critical enzymes that determine the specificity of substrate
      recognition. The E3 ligase Itch was identified from a mutant mouse which displays
      skin scratching and abnormal immune disorders. In the past few years, much
      progress has been made in our understanding of Itch-promoted protein
      ubiquitination, modulation of its ligase activity by upstream kinases, and the
      kinase-ligase interaction in T cell differentiation and tolerance induction.

PMID- 17433713
TI  - Postnatal alterations of the inhibitory synaptic responses recorded from cortical
      pyramidal neurons in the Lis1/sLis1 mutant mouse.
AB  - Mutations in the mouse Lis1 gene produce severe alterations in the developing
      cortex. We have examined some electrophysiological responses of cortical
      pyramidal neurons during the early postnatal development of Lis/sLis1 mutant
      mice. In P7 and P30 Lis1/sLis1 neurons we detected a lower frequency and slower
      decay phase of mIPSCs, and at P30 the mIPSCs amplitude and the action potential
      duration were reduced. Zolpidem (an agonist of GABAA receptors containing the
      alpha1 subunit) neither modified the amplitude nor the decay time of mIPSCs at P7
      in Lis1/sLis1 neurons, whereas it increased the decay time at P30. The levels of
      GABAA receptor alpha1 subunit mRNA were reduced in the Lis1/sLis1 brain at P7 and
      P30, whereas reduced levels of the corresponding protein were only found at P7.
      These results demonstrate the presence of functional alterations in the postnatal
      Lis1/sLis1 cortex and point to abnormalities in GABAA receptor subunit switching
      processes during postnatal development.

PMID- 17433712
TI  - The sodium channel Nav1.5a is the predominant isoform expressed in adult mouse
      dorsal root ganglia and exhibits distinct inactivation properties from the full
      length Nav1.5 channel.
AB  - Nav1.5 is the principal voltage-gated sodium channel expressed in heart, and is
      also expressed at lower abundance in embryonic dorsal root ganglia (DRG) with
      little or no expression reported postnatally. We report here the expression of
      Nav1.5 mRNA isoforms in adult mouse and rat DRG. The major isoform of mouse DRG
      is Nav1.5a, which encodes a protein with an IDII/III cytoplasmic loop reduced by
      53 amino acids. Western blot analysis of adult mouse DRG membrane proteins
      confirmed the expression of Nav1.5 protein. The Na+ current produced by the
      Nav1.5a isoform has a voltage-dependent inactivation significantly shifted to
      more negative potentials (by approximately 5 mV) compared to the full-length
      Nav1.5 when expressed in the DRG neuroblastoma cell line ND7/23. These results
      imply that the alternatively spliced exon 18 of Nav1.5 plays a role in channel
      inactivation and that Nav1.5a is likely to make a significant contribution to
      adult DRG neuronal function.

PMID- 17433714
TI  - Reliability of standard health assessment instruments in a large, population
      based cohort study.
AB  - PURPOSE: The Millennium Cohort Study began in 2001 using mail and Internet
      questionnaires to gather occupational and environmental exposure, behavioral risk
      factor, and health outcome data from a large, population-based US military
      cohort. Standardized instruments, including the Patient Health Questionnaire, the
      Medical Outcomes Study Short Form-36 for Veterans, and the Posttraumatic Stress
      Disorder (PTSD) Checklist-Civilian Version, have been validated in various
      populations. The purpose of this study was to investigate internal consistency of
      standardized instruments and concordance of responses in a test-retest setting.
      METHODS: Cronbach alpha coefficients were used to investigate the internal
      consistency of standardized instruments among 76,742 participants. Kappa
      statistics were calculated to measure stability of aggregated responses in a
      subgroup of 470 participants who voluntarily submitted an additional survey
      within 6 months of their original submission. RESULTS: High internal consistency
      was found for 14 of 16 health components, with lower internal consistency found
      among two alcohol components. Substantial test-retest stability was observed for
      stationary variables, while moderate stability was found for more dynamic
      variables that measured conditions with low prevalence. CONCLUSIONS: These
      results substantiate internal consistency and stability of several standard
      health instruments applied to this large cohort. Such reliability analyses are
      vital to the integrity of long-term outcome studies.

PMID- 17433715
TI  - Physical continuity of the perimysium from myofibers to tendons: involvement in
      lateral force transmission in skeletal muscle.
AB  - Advances in muscle physiology suggest that the perimysium plays a role in the
      transmission of lateral contractile forces. This hypothesis is strongly supported
      by our recent demonstration of the existence of "Perimysial Junctional Plates" in
      bovine Flexor carpi radialis muscle [Passerieux, E., Rossignol, R., Chopard, A.,
      Carnino, A., Marini, J.F., Letellier, T., Delage, J.P. 2006. Structural
      organization of the perimysium in bovine skeletal muscle: junctional plates and
      associated intracellular subdomains. J. Struct. Biol. 154 (2), 206-216] However,
      the overall organization of the perimysium collagen network, as well as its
      continuity and heterogeneity, have still not been described in detail throughout
      the entire muscle. We used an extension of the standard NaOH digestion technique
      and scanning electron microscopy to analyze perimysium architecture in bovine
      Flexor carpi radialis muscle. First, we observed that the perimysium is made of a
      highly ordered network of collagen fibers, binding the myofibers from tendon to
      tendon. We identified basic collagen cable structures, characterized by a
      straight portion (3 cm long) in the direction of the myofibers and a curved
      terminal portion at 60 degrees. These cables reach the myofiber surface at the
      level of the previously described "Perimysial Junctional Plates". At a higher
      level of organization, these cables stick together to form the walls of numerous
      tubes arranged in a overlapping honeycomb pattern around the myofibers. At the
      ends of these tubes, the straight portions of the collagen cables ramify in large
      bundles that merge with the tendons. Taken together, these observations identify
      four levels of organization in the perimysium: (i) Perimysial Junctional Plates
      that constitute the focal attachment between the perimysium and the myofibers,
      (ii) collagen plexi attaching adjacent myofibers, (iii) a loose lattice of large
      interwoven fibers, and (iv) honeycomb tubes connecting two tendons. This spatial
      arrangement of the perimysium supports the view of a complex pattern of lateral
      force transmission from myofibers to tendons and adjacent muscles.

PMID- 17433716
TI  - Molecular cloning and expression analysis of sea bass (Dicentrarchus labrax L.)
      tumor necrosis factor-alpha (TNF-alpha).
AB  - In the search for pro-inflammatory genes in sea bass a TNF-alpha gene was cloned
      and sequenced. The sea bass TNF-alpha (sbTNF-alpha) putative protein conserves
      the TNF-alpha family signature, as well as the two cysteines usually involved in
      the formation of a disulfide bond. The mouse TNF-alpha Thr-Leu cleavage sequence
      and a potential transmembrane domain were also found, suggesting that sbTNF-alpha
      exists as two forms: a approximately 28 kDa membrane-bound form and a
      approximately 18.4 kDa soluble protein. The single copy sbTNF-alpha gene contains
      a four exon-three intron structure similar to other known TNF-alpha genes.
      Homology modeling of sbTNF-alpha is compatible with the trimeric quaternary
      architecture of its mammalian counterparts. SbTNF-alpha is constitutively
      expressed in several unstimulated tissues, and was not up-regulated in the spleen
      and head-kidney, in response to UV-killed Photobacterium damselae subsp.
      piscicida. However, an increase of sbTNF-alpha expression was detected in the
      head-kidney during an experimental infection using the same pathogen.

PMID- 17433717
TI  - Gradations of awareness in a modified sequence learning task.
AB  - We argue performance in the serial reaction time (SRT) task is associated with
      gradations of awareness that provide examples of fringe consciousness [Mangan, B.
      (1993b). Taking phenomenology seriously: the "fringe" and its implications for
      cognitive research. Consciousness and Cognition, 2, 89-108, Mangan, B. (2003).
      The conscious "fringe": Bringing William James up to date. In B. J. Baars, W. P.
      Banks & J. B. Newman (Eds.), Essential sources in the scientific study of
      consciousness (pp. 741-759). Cambridge, MA: The MIT Press.], and address
      limitations of the traditional SRT procedure, including criticism of exclusion
      generation tasks. Two experiments are conducted with a modified SRT procedure
      where irrelevant stimulus attributes obscure the sequence rule. Our modified
      paradigm, which includes a novel exclusion task, makes it easier to demonstrate a
      previously controversial influence of response stimulus interval (RSI) on
      awareness. It also allows identification of participants showing fringe
      consciousness rather than explicit sequence knowledge, as reflected by
      dissociations between different awareness measures. The NEO-PI-R variable
      Openness to Feelings influenced the diversity of subjective feelings reported
      during two awareness measures, but not the degree of learning and awareness as
      previously found with traditional SRT tasks [Norman, E., Price, M. C., & Duff, S.
      C. (2006). Fringe consciousness in sequence learning: the influence of individual
      differences. Consciousness and Cognition, 15(4), 723-760.]. This suggests
      possible distinctions between two components of fringe consciousness.

PMID- 17433718
TI  - Temporal judgements of internal and external events in persons with and without
      autism.
AB  - When participants make judgments about the onset of self-initiated movements they
      typically report the movement occurred earlier than it had [Obhi, S. S., &
      Haggard, P. (2004). Free will and free won't. American Scientific, 92, 358-365.].
      One interpretation is that feed-forward processes lead to awareness of the
      movement prior to execution. Because individuals with autism experience reduced
      preparatory activity prior to a voluntary movement, the present study sought to
      determine whether these anticipatory biases are exhibited by persons with autism.
      Participants watched a dot move in a circle and pressed the spacebar any time
      after one revolution. A tone either followed the participants' voluntary movement
      or was computer generated. Participants in both groups made anticipatory
      judgements regarding movement initiation ( approximately 100 ms). When the
      movement and tone occurred together this anticipatory bias was also present,
      regardless of which event participants focused on. Individuals with autism appear
      to have access to a similar representation of voluntary movements, however this
      representation may be more variable.

PMID- 17433719
TI  - A phylogeny of Anisophylleaceae based on six nuclear and plastid loci: ancient
      disjunctions and recent dispersal between South America, Africa, and Asia.
AB  - The Anisophylleaceae comprise 29-34 species of shrubs and trees occurring in
      lowland forests and swamps in tropical Africa, Asia, and South America. These
      species are placed in four genera with disjunct geographic distributions;
      Anisophyllea has 25-30 species in South America, Africa, and Malesia;
      Combretocarpus has one species in Sumatra and Borneo; Poga one species in
      equatorial Africa; and Polygonanthus two in the Amazon Basin. Here we use a
      phylogeny based on six nuclear and plastid loci sequenced for 15 species
      representing the four genera to infer their relationships and the relative and
      absolute ages of the range disjunctions. Combretocarpus is sister to the other
      three genera, and Polygonanthus then sister to Poga and Anisophyllea.
      Ansiophyllea, represented by 12 species from all three continents, is
      monophyletic. A relaxed Bayesian clock calibrated with the oldest fossils from a
      relevant outgroup, Tetramelaceae, suggests that the disjunctions between
      Combretocarpus, Poga, and Polygonanthus date back to the Cretaceous, Mid-, and
      Upper Eocene, whereas the intercontinental disjunctions within Anisophyllea
      appear to date back only some 22-23 million years and thus probably result from
      long-distance dispersal.

PMID- 17433720
TI  - A rapid diversification of rainforest trees (Guatteria; Annonaceae) following
      dispersal from Central into South America.
AB  - Several recent studies have suggested that a substantial portion of today's plant
      diversity in the Neotropics has resulted from the dispersal of taxa into that
      region rather than vicariance, but more data are needed to substantiate this
      claim. Guatteria (Annonaceae) is, with 265 species, the third largest genus of
      Neotropical trees after Inga (Fabaceae) and Ocotea (Lauraceae), and its
      widespread distribution and frequent occurrence makes the genus an excellent
      model taxon to study diversification patterns. This study reconstructed the
      phylogeny of Guatteria and inferred three major biogeographical events in the
      history of the genus: (1) a trans-oceanic Miocene migration from Central into
      South America before the closing of the Isthmus of Panama; (2) a major
      diversification of the lineage within South America; and (3) several migrations
      of South American lineages back into Central America via the closed Panamanian
      land bridge. Therefore, Guatteria is not an Amazonian centred-genus sensu Gentry
      but a major Miocene diversification that followed its dispersal into South
      America. This study provides further evidence that migration into the Neotropics
      was an important factor in the historical assembly of its biodiversity.
      Furthermore, it is shown that phylogenetic patterns are comparable to those found
      in Ocotea and Inga and that a closer comparison of these genera is desirable.

PMID- 17433721
TI  - Evidence for placing the false gharial (Tomistoma schlegelii) into the family
      Gavialidae: inferences from nuclear gene sequences.
AB  - The extant crocodylians comprise 23 species divided among three families,
      Alligatoridae, Crocodylidae, and Gavialidae. Currently, based on morphological
      data sets, Tomistoma schlegelii (false gharial) is placed within the family
      Crocodylidae. Molecular data sets consistently support a sister-taxon
      relationship of T. schlegelii with Gavialis gangeticus (Indian Gharial), which is
      the sole species in Gavialidae. To elucidate the placement of T. schlegelii
      within the extant crocodylians, we have sequenced 352bp of the dentin matrix
      protein 1 (DMP1) nuclear gene in 30 individuals and 424bp of the nuclear gene C
      mos in 74 individuals. Molecular analysis of the DMP1 data set indicates that it
      is highly conserved within the Crocodylia. Of special note is a seven base-pair
      indel (GTGCTTT) shared by T. schlegelii and G. gangeticus, that is absent in the
      genus Crocodylus, Osteolaemus, and Mecistops. To date, C-mos is the largest
      molecular data set analyzed for any crocodylian study including multiple samples
      from all representatives of the eight extant genera. Analysis of these molecular
      data sets, both as individual gene sequences and concatenated sequences, support
      the hypothesis that T. schlegelii should be placed within the family Gavialidae.

PMID- 17433722
TI  - Phylogenetic relationships among Bursaphelenchus species (Nematoda:
      Parasitaphelenchidae) inferred from nuclear ribosomal and mitochondrial DNA
      sequence data.

PMID- 17433723
TI  - Conflicting phylogenetic signal of nuclear vs mitochondrial DNA markers in
      midwife toads (Anura, Discoglossidae, Alytes): deep coalescence or ancestral
      hybridization?

PMID- 17433724
TI  - Families of Cobitoidea (Teleostei; Cypriniformes) as revealed from nuclear
      genetic data and the position of the mysterious genera Barbucca, Psilorhynchus,
      Serpenticobitis and Vaillantella.

PMID- 17433725
TI  - Origins of social parasitism: the importance of divergence ages in phylogenetic
      studies.
AB  - Phylogenetic studies on insect social parasites have found very close host
      parasite relationships, and these have often been interpreted as providing
      evidence for sympatric speciation. However, such phylogenetic inferences are
      problematic because events occurring after the origin of parasitism, such as
      extinction, host switching and subsequent speciation, or an incomplete sampling
      of taxa, could all confound the interpretation of phylogenetic relationships.
      Using a tribe of bees where social parasitism has repeatedly evolved over a wide
      time-scale, we show the problems associated with phylogenetic inference of
      sympatric speciation. Host-parasite relationships of more ancient species appear
      to support sympatric speciation, whereas in a case where parasitism has evolved
      very recently, sympatric speciation can be ruled out. However, in this latter
      case, a single extinction event would have lead to relationships that support
      sympatric speciation, indicating the importance of considering divergence ages
      when analysing the modes of social parasite evolution.

PMID- 17433726
TI  - Perioperative fluctuations of lamotrigine serum levels in patients undergoing
      epilepsy surgery.
AB  - Some patients undergoing epilepsy surgery suffer from early postoperative
      seizures which may have a negative impact on later outcome. Factors contributing
      to these seizures have not to date been examined systematically. We hypothesized
      that reduction of postoperative serum levels of antiepileptic drugs (AED) may be
      one risk factor for early postoperative seizures. METHODS: We retrospectively
      reviewed medical records from 20 patients treated with lamotrigine (LTG) who
      underwent epilepsy surgery between January 1997 and February 2004. Demographic
      data, anaesthesiological and surgical procedures, co-medication, and pre- as well
      as one or more postoperative LTG serum levels were evaluated. RESULTS: We found a
      significant decrease in LTG serum levels, amounting to more than 20% (mean 46%,
      range 21.9-69.1%), in 16 of 20 patients (80%). Six patients (30%) suffered from
      seizures in the first 2 weeks after surgery. In three patients, postoperative
      seizures occurred isochronically with the LTG serum level nadir. The magnitude of
      the reduction in serum levels was not influenced by age, sex, duration of the
      operation, the type of anaesthetic drugs or the postoperative co-medication.
      DISCUSSION: Reductions in LTG serum levels are a relevant contributing factor for
      early postoperative seizures. Postoperative alteration of the gastrointestinal
      motility and transient time leading to delayed absorption and reduced
      bioavailability of AED may be a major risk factor. Therefore, close monitoring of
      postoperative LTG serum levels is necessary and should lead to a temporary dose
      augmentation and/or anticonvulsant co-medication with benzodiazepines in case of
      a pronounced reduction of serum levels.

PMID- 17433727
TI  - Human SIRT1: a potential biomarker for tumorigenesis?
AB  - Accumulating body of evidence reveals that hSIRT1, an NAD(+)-dependent protein
      deacetylase, is involved in regulating numerous biological processes. Therefore
      cellular functions of hSIRT1 are highly pleiotropic. The integrated hypothetical
      mechanisms of hSIRT1 action contributing to regulating cellular senescence and
      longevity have been proposed. Based on recent evidence, I propose that hSIRT1 is
      a potential biomarker for tumorigenesis.

PMID- 17433728
TI  - Pannexin-1-mediated recognition of bacterial molecules activates the cryopyrin
      inflammasome independent of Toll-like receptor signaling.
AB  - Cryopyrin is essential for caspase-1 activation triggered by Toll-like receptor
      (TLR) ligands in the presence of adenosine triphosphate (ATP). However, the
      events linking bacterial products and ATP to cryopyrin remain unclear. Here we
      demonstrate that cryopyrin-mediated caspase-1 activation proceeds independently
      of TLR signaling, thus dissociating caspase-1 activation and IL-1beta secretion.
      Instead, caspase-1 activation required pannexin-1, a hemichannel protein that
      interacts with the P2X(7) receptor. Direct cytosolic delivery of multiple
      bacterial products including lipopolysaccharide, but not flagellin, induced
      caspase-1 activation via cryopyrin in the absence of pannexin-1 activity or ATP
      stimulation. However, unlike Ipaf-dependent caspase-1 activation, stimulation of
      the pannexin-1-cryopyrin pathway by several intracellular bacteria was
      independent of a functional bacterial type III secretion system. These results
      provide evidence for cytosolic delivery and sensing of bacterial molecules as a
      unifying model for caspase-1 activation and position pannexin-1 as a mechanistic
      link between bacterial stimuli and the cryopyrin inflammasome.

PMID- 17433729
TI  - Molecular evidence for hierarchical transcriptional lineage priming in fetal and
      adult stem cells and multipotent progenitors.
AB  - Recent studies implicated the existence of adult lymphoid-primed multipotent
      progenitors (LMPPs) with little or no megakaryocyte-erythroid potential,
      questioning common myeloid and lymphoid progenitors as obligate intermediates in
      hematopoietic stem cell (HSC) lineage commitment. However, the existence of LMPPs
      remains contentious. Herein, global and single-cell analyses revealed a
      hierarchical organization of transcriptional lineage programs, with
      downregulation of megakaryocyte-erythroid genes from HSCs to LMPPs, sustained
      granulocyte-monocyte priming, and upregulation of common lymphoid (but not B and
      T cell-specific) genes. These biological and molecular relationships, implicating
      almost mutual exclusion of megakaryocyte-erythroid and lymphoid pathways, are
      established already in fetal hematopoiesis, as evidenced by existence of LMPPs in
      fetal liver. The identification of LMPPs and hierarchically ordered
      transcriptional activation and downregulation of distinct lineage programs is
      compatible with a model for HSC lineage commitment in which the probability for
      undergoing different lineage commitment fates changes gradually when progressing
      from HSCs to LMPPs.

PMID- 17433731
TI  - Letter to the editor, re: Nylaende M, Abdelnoor M, Stranden E, Morken B, Sandbaek
      G, Risum O, et al. The Oslo balloon angioplasty versus conservative treatment
      study (OBACT)--the 2-years results of a single centre, prospective, randomised
      study in patients with intermittent claudication. Eur J Vasc Endovasc Surg.
      2007;33:3-12.

PMID- 17433730
TI  - Nod1-mediated innate immune recognition of peptidoglycan contributes to the onset
      of adaptive immunity.
AB  - Recent evidence has suggested that signals other than those from Toll-like
      receptors (TLRs) could contribute to the elicitation of antigen-specific
      immunity. Therefore, we examined the role of the Nod-like receptor (NLR) family
      member, Nod1, in the generation of adaptive immune responses. Our findings show
      that innate immune sensing of peptidoglycan by Nod1 is key for priming antigen
      specific T cell immunity and subsequent antibody responses in vivo. Nod1
      stimulation alone was sufficient to drive antigen-specific immunity with a
      predominant Th2 polarization profile. In conjunction with TLR stimulation,
      however, Nod1 triggering was required to instruct the onset of Th1 and Th2 as
      well as Th17 immune pathways. Cells outside of the hematopoietic lineage provided
      the early signals necessary to orchestrate the development of Nod1-dependent
      immune responses. These findings highlight Nod1 as a key innate immune trigger in
      the local tissue microenvironment that drives the development of adaptive
      immunity.

PMID- 17433732
TI  - Acute limb ischemia in elderly patients: can iloprost be useful as an adjuvant to
      surgery? Results from the ILAILL study.
AB  - OBJECTIVES: To evaluate the effects of iloprost, in addition to surgery, on the
      outcome of acute lower limb ischemia (ALLI). DESIGN: Post-hoc analysis of a
      randomized, double-blind, placebo-controlled study. METHODS: In the context of
      the ILAILL (ILoprost in Acute Ischemia of Lower Limbs) study, 192 elderly
      patients (>70 years old) undergoing surgery for ALLI were assigned to receive
      perioperative iloprost (intra-arterial, intra-operative bolus of 3000 ng, plus
      intravenous infusion of 0.5-2.0 ng/kg/min for six hours/day for 4-7 days
      following surgery), or placebo (iloprost: n=100; placebo: n=92). Patients were
      followed-up for three-months following surgical revascularization. RESULTS: The
      combined incidence of death and amputation (primary study end-point) was
      significantly reduced in patients treated with iloprost (16.0% vs 27.2% in the
      placebo group; hazard ratio 1.99, 95% confidence interval 1.05-3.75, p=0.03). A
      statistically significant lower mortality (6.0%) was reported in patients
      receiving iloprost, compared to controls (15.2%) (hazard ratio 2.93, 1.11-7.71,
      p=0.03). The overall incidence of death and major cardiovascular events was lower
      in patients receiving iloprost compared to those assigned placebo (24.0% and
      35.9%, respectively), at the limits of statistical significance (relative risk
      1.64, 0.97-2.79, p=0.06). CONCLUSIONS: These results confirm the poor outcome in
      elderly patients with ALLI. Based on a subgroup analysis iloprost, as an adjuvant
      to surgery, appears to reduce the combined end-point of death and amputation.

PMID- 17433734
TI  - Molecular epidemiology of Streptococcus zooepidemicus infection in naturally
      occurring equine respiratory disease.
AB  - The objective of the study was to characterise the molecular epidemiology of
      Streptococcus zooepidemicus infection among isolates collected sequentially from
      recently weaned, pasture maintained Welsh mountain ponies with naturally
      occurring respiratory disease. Weekly nasopharyngeal and tracheal lavage
      samplings over a 10-week period were conducted in 29 ponies. Two PCR typing
      methods based on characterisation of the M-protein hypervariable (HV) region and
      the 16S-23S rRNA gene intergenic spacer were then applied to isolates of S.
      zooepidemicus recovered from nasopharyngeal swab and tracheal wash samples. S.
      zooepidemicus infection was highly prevalent during the study, being isolated
      from 94% of tracheal washes and 88% of nasopharyngeal swabs. Among 39 different
      S. zooepidemicus types isolated, more were isolated from the trachea (n=33) than
      the nasopharynx (n=27). There was evidence from temporal patterns of infection
      for clonal succession over time by the more prevalent S. zooepidemicus types.
      Novel S. zooepidemicus types were identified, including previously untyped HV
      regions and intra-strain multiples of both the HV region and intergenic spacer
      types.

PMID- 17433733
TI  - Deletion of the human beta-globin LCR 5'HS4 or 5'HS1 differentially affects beta
      like globin gene expression in beta-YAC transgenic mice.
AB  - A 213 kb human beta-globin locus yeast artificial chromosome (beta-YAC) was
      modified by homologous recombination to delete 2.9 kb of cross-species conserved
      sequence similarity encompassing the LCR 5' hypersensitive site (HS) 4
      (Delta5'HS4 beta-YAC). In three transgenic mouse lines, completion of the gamma-
      to beta-globin switch during definitive erythropoiesis was delayed relative to
      wild-type beta-YAC mice. In addition, quantitative per-copy human beta-like
      globin mRNA levels were similar to wild-type beta-YAC transgenic lines, although
      beta-globin gene expression was slightly decreased in the day 12 fetal liver of
      Delta5'HS4 beta-YAC mice. A 0.8 kb 5'HS1 fragment was similarly deleted in the
      YAC. Three Delta5'HS1 beta-YAC transgenic lines were established. epsilon-globin
      gene expression was markedly reduced, approximately 16 fold, during primitive
      erythropoiesis compared to wild-type beta-YAC mice, but gamma-globin expression
      levels were unaffected. However, during the fetal stage of definitive
      erythropoiesis, gamma-globin gene expression was decreased approximately 4 fold
      at day 12 and approximately 5 fold at day 14. Temporal developmental expression
      profiles of the beta-like globin genes were unaffected by deletion of 5'HS1.
      Decreased expression of the epsilon- and gamma-globin genes is the first
      phenotype ascribed to a 5'HS1 mutation in the human beta-globin locus, suggesting
      that this HS does indeed have a role in LCR function beyond simply a combined
      synergism with the other LCR HSs.

PMID- 17433735
TI  - Effects of bovine necrotic vulvovaginitis on productivity in a dairy herd in
      Israel.
AB  - Bovine necrotic vulvovaginitis (BNVV) is characterized by the development of a
      necrotic vulvovaginal lesion, almost exclusively in post-parturient first
      lactation cows, associated with Porphyromonas levii. The scope of this survey was
      to evaluate the impact of BNVV on herd productivity as a means to rationally
      evaluate the resources that should be allocated in dealing with the syndrome.
      During an outbreak of BNVV in a dairy herd, following the introduction of a large
      number of cows from another farm, the impact of the animals' origin (local or
      transferred) and BNVV (positive or negative) upon involuntary culling rate, milk
      yield and days between pregnancies were assessed. The results indicated that the
      number of days between pregnancies was significantly higher in first-lactation
      cows with BNVV but was not influenced by the other independent variables. None of
      the other variables included in this survey had any effect on the involuntary
      culling rate and milk yield.

PMID- 17433736
TI  - The paradox of modern animal husbandry and lameness.

PMID- 17433738
TI  - Position paper of the European Federation of IASP Chapters (EFIC) on the subject
      of pain management.
AB  - Among the complaints that bring patients to see their physician, pain in its
      various manifestations is the most frequent. In spite of this, pain is often not
      adequately addressed or managed. The aim of this position paper is to present the
      viewpoint and recommendations of EFIC on the subject of pain management. Our
      overall objective is to encourage adoption by architects of healthcare systems in
      Europe and worldwide of a set of specific recommendations. Every patient is
      entitled to the implementation of these recommendations in a professional,
      accessible and timely manner.

PMID- 17433737
TI  - Seizures in Rett syndrome: an overview from a one-year calendar study.
AB  - BACKGROUND: Rett syndrome is a neurodevelopmental disorder mainly affecting
      females. It is principally caused by mutations in the MECP2 gene. Seizures occur
      in about 80% of subjects but there has been little research into the factors
      contributing to their frequency. AIMS: To investigate seizure frequency in Rett
      syndrome and its relationship with other factors, including genetic
      characteristics and the use of anti-epileptic drugs. METHODS: Information on
      daily seizure occurrence and health service utilization and monthly anti
      epileptic drug use was provided on 162 Rett syndrome cases for a calendar year.
      Age at onset of seizures, developmental history and other clinical and genetic
      characteristics were obtained from a contemporaneously completed questionnaire
      and from the Australian Rett Syndrome Database. Negative binomial regression was
      used to investigate factors associated with seizure rates. RESULTS: Seizure rates
      were highest in the 7-12 year age group. They were lower in those with p.R294X,
      p.R255X mutations and C terminal mutations. Those who had early developmental
      problems and poorer mobility had higher seizure rates as did those with greater
      clinical severity and poorer functional ability. Many different combinations of
      medications were being used with carbamazepine, sodium valproate and lamotrigine
      either singly or in combination with another being the most common. CONCLUSIONS:
      Seizure frequency in Rett syndrome is age-dependent, more common in those with
      more severe early developmental problems and influenced by mutation type.

PMID- 17433739
TI  - Is distraction less effective when pain is threatening? An experimental
      investigation with the cold pressor task.
AB  - Distraction is a commonly used strategy to control pain. However there is doubt
      about its effectiveness as a clinical tool, and results from both experimental
      and clinical studies remain inconclusive. Recent theoretical advancements suggest
      that distraction of attention may be less effective when pain is threatening. The
      aim of the present study was to experimentally investigate this hypothesis. Pain
      free volunteers (N=101) participated in a cold pressor test. Half of the
      participants simultaneously performed a cognitive distraction task, the other
      half did not. The threat value of the pain was manipulated by means of verbal
      information. The results showed that distraction resulted in less attention to
      the pain and lower pain ratings once the cold pressor procedure was halted. The
      hypothesis that the effectiveness of distraction is modulated by the threat value
      of pain could not be confirmed. However, threatening information increased
      catastrophic thoughts and anxiety, and interfered with performance on the
      distraction task. These findings suggest that caution is required in using
      distraction as a pain control strategy when the threat value is high, because
      fearful appraisal of pain is associated with less engagement in distraction
      tasks.

PMID- 17433740
TI  - Unilateral NMR study of a XVI century wall painted.
AB  - Wall paintings in the XVI century Serra Chapel in the "Chiesa di Nostra Signora
      del Sacro Cuore" Rome, have been studied using unilateral NMR. In order to map
      the distribution of moisture content in the wall painted, a large number of Hahn
      echo measurements, covering large areas of the wall painting were performed.
      Because the intensity of the Hahn echo is proportional to the amount of moisture
      in the area under study, the experimental data were transformed into 2D gradient
      colour maps which allowed an easy visualization of the moisture content of the
      wall. The state of conservation of the wall painting was monitored using T2
      measurements specially with regards to outcropping salt.

PMID- 17433741
TI  - Frequency-selective quantitation of short-echo time 1H magnetic resonance
      spectra.
AB  - Accurate and efficient filtering techniques are required to suppress large
      nuisance components present in short-echo time magnetic resonance (MR) spectra.
      This paper discusses two powerful filtering techniques used in long-echo time MR
      spectral quantitation, the maximum-phase FIR filter (MP-FIR) and the Hankel
      Lanczos Singular Value Decomposition with Partial ReOrthogonalization (HLSVD
      PRO), and shows that they can be applied to their more complex short-echo time
      spectral counterparts. Both filters are validated and compared through extensive
      simulations. Their properties are discussed. In particular, the capability of MP
      FIR for dealing with macromolecular components is emphasized. Although this
      property does not make a large difference for long-echo time MR spectra, it can
      be important when quantifying short-echo time spectra.

PMID- 17433742
TI  - Simultaneous acquisition of magnetic resonance spectroscopy (MRS) data and
      positron emission tomography (PET) images with a prototype MR-compatible, small
      animal PET imager.
AB  - Multi-modality imaging (such as PET-CT) is rapidly becoming a valuable tool in
      the diagnosis of disease and in the development of new drugs. Functional images
      produced with PET, fused with anatomical images created by MRI, allow the
      correlation of form with function. Perhaps more exciting than the combination of
      anatomical MRI with PET, is the melding of PET with MR spectroscopy (MRS). Thus,
      two aspects of physiology could be combined in novel ways to produce new insights
      into the physiology of normal and pathological processes. Our team is developing
      a system to acquire MRI images and MRS spectra, and PET images contemporaneously.
      The prototype MR-compatible PET system consists of two opposed detector heads
      (appropriate in size for small animal imaging), operating in coincidence mode
      with an active field-of-view of approximately 14 cm in diameter. Each detector
      consists of an array of LSO detector elements coupled through a 2-m long fiber
      optic light guide to a single position-sensitive photomultiplier tube. The use of
      light guides allows these magnetic field-sensitive elements of the PET imager to
      be positioned outside the strong magnetic field of our 3T MRI scanner. The PET
      scanner imager was integrated with a 12-cm diameter, 12-leg custom, birdcage
      coil. Simultaneous MRS spectra and PET images were successfully acquired from a
      multi-modality phantom consisting of a sphere filled with 17 brain relevant
      substances and a positron-emitting radionuclide. There were no significant
      changes in MRI or PET scanner performance when both were present in the MRI
      magnet bore. This successful initial test demonstrates the potential for using
      such a multi-modality to obtain complementary MRS and PET data.

PMID- 17433743
TI  - Comparisons of EPR imaging and T1-weighted MRI for efficient imaging of nitroxyl
      contrast agents.
AB  - The resolution and signal to noise ratio of EPR imaging and T(1)-weighted MRI
      were compared using an identical phantom. Several solutions of nitroxyl contrast
      agents with different EPR spectral shapes were tested. The feasibility of T(1)
      weighted MRI to detect nitroxyl contrast agents was described. T(1)-weighted MRI
      can detect nitroxyl contrast agents with a complicated EPR spectrum easier and
      quicker; however, T(1)-weighted MRI has less quantitative ability especially for
      lipophilic nitroxyl contrast agents, because T(1)-relaxivity, i.e. accessibility
      to water, is affected by the hydrophilic/hydrophobic micro-environment of a
      nitroxyl contrast agent. The less quantitative ability of T(1)-weighted MRI may
      not be a disadvantage of redox imaging, which obtains reduction rate of a
      nitroxyl contrast. Therefore, T(1)-weighted MRI has a great advantage to check
      the pharmacokinetics of newly modified and/or designed nitroxyl contrast agents.

PMID- 17433744
TI  - A realization of digital wireless transmission for MRI signals based on 802.11b.
AB  - In this paper, a digital wireless transmission system based on 802.11b standard
      for magnetic resonance imaging (MRI) application is designed and built for the
      first time to eliminate the interference aroused by coil array cables. The
      analysis shows that the wireless receiver has a very high sensitivity to detect
      MRI signals. The modulation technique of differential quadrature phase shift
      keyed (DQPSK) can be applied to MRI data transmission with rate of 2 Mbps and
      bandwidth of 2 MHz. The bench test verifies that this wireless link has a dynamic
      range over 86 dB supporting up to 3 T MRI system data transmission. The 2D spin
      echo imaging of phantom is performed and the SNR of the image obtained by the
      wireless transmission can be comparable with that got by the coaxial cables.

PMID- 17433745
TI  - Volume learning algorithm significantly improved PLS model for predicting the
      estrogenic activity of xenoestrogens.
AB  - Volume learning algorithm (VLA) artificial neural network and partial least
      squares (PLS) methods were compared using the leave-one-out cross-validation
      procedure for prediction of relative potency of xenoestrogenic compounds to the
      estrogen receptor. Using Wilcoxon signed rank test we showed that VLA
      outperformed PLS by producing models with statistically superior results for a
      structurally diverse set of compounds comprising eight chemical families. Thus,
      CoMFA/VLA models are successful in prediction of the endocrine disrupting
      potential of environmental pollutants and can be effectively applied for testing
      of prospective chemicals prior their exposure to the environment.

PMID- 17433746
TI  - Seasonal variations in the biochemical composition and lipoperoxidation of
      Hyalella curvispina (Crustacea, Amphipoda).
AB  - We assessed the effect of seasonal variations on the biochemical composition and
      lipoperoxidation of an amphipod crustacean, Hyalella curvispina, which inhabits
      the coastal plain of the state of Rio Grande do Sul, and correlated this with
      information on the biology of the species. The animals were collected monthly
      from September 2003 to August 2005, in Gentil Lagoon, Tramandai, Rio Grande do
      Sul, Brazil. Glycogen levels, total proteins, total lipids, triglycerides, and
      lipoperoxidation were measured for each sex separately. The results suggest that
      these animals have seasonal storage and degradation of the energy substrates
      investigated. During summer, glycogen, total lipids, and triglycerides were
      stored, and were utilized especially during autumn and winter. Proteins were
      utilized differently in males and females. Females stored proteins especially in
      spring and used them in summer; whereas males stored proteins especially in
      spring and used them in winter. The levels of lipoperoxidation during the year
      differed between females and males. These variations may be related to biotic
      factors (e.g., reproduction period and others) and to abiotic factors (e.g.,
      water temperature, salinity and others).

PMID- 17433747
TI  - Adenosine does not save the heart of anoxia-tolerant vertebrates during prolonged
      oxygen deprivation.
AB  - Despite adenosine being regarded as an important signaling molecule capable of
      coordinating ATP supply and demand during periods of oxygen deprivation in anoxia
      intolerant mammals, the importance of adenosinergic cardiovascular control in
      anoxia-tolerant vertebrates is poorly understood. Here, we report on
      adenosinergic cardiovascular control during normoxia and prolonged (hours to
      days) oxygen deprivation for three vertebrate species tolerant of severe
      hypoxia/anoxia, the closely related common (Cyprinus carpio) and crucian
      (Carassius carassius) carp, and the freshwater turtle (Trachemys scripta). Using
      an intra-arterial injection of the non-specific adenosine receptor antagonist
      aminophylline while measuring cardiac output (Q), heart rate (f(H)) and arterial
      blood pressure, we establish that adenosinergic cardiovascular control is
      unimportant during prolonged anoxia in the freshwater turtle (6 h at 21 degrees C
      and 14 d at 5 degrees C) and the crucian carp (5 d at 8 degrees C). In contrast,
      adenosinergic control contributes to the down-regulation of cardiac activity
      exhibited by 5 degrees C-acclimated common carp during a 12.5 h severe hypoxia
      (<0.3 mg O2 l(-1)) exposure. Specifically, aminophylline injection resulted in
      significant increases in f(H) and Q, and a decrease in total peripheral
      resistance. These species-specific differences in adenosinergic cardiovascular
      control during prolonged periods of oxygen deprivation may be related to
      differences displayed by these three species in their anoxia tolerance and
      survival strategies.

PMID- 17433748
TI  - Allelic and non-allelic heterogeneities in pyridoxine dependent seizures revealed
      by ALDH7A1 mutational analysis.
AB  - Pyridoxine dependent seizure (PDS) is a disorder of neonates or infants with
      autosomal recessive inheritance characterized by seizures, which responds to
      pharmacological dose of pyridoxine. Recently, mutations have been identified in
      the ALDH7A1 gene in Caucasian families with PDS. To elucidate further the genetic
      background of PDS, we screened for ALDH7A1 mutations in five PDS families
      (patients 1-5) that included four Orientals. Diagnosis as having PDS was
      confirmed by pyridoxine-withdrawal test. Exon sequencing analysis of patients 1-4
      revealed eight ALDH7A1 mutations in compound heterozygous forms: five missense
      mutations, one nonsense mutation, one point mutation at the splicing donor site
      in intron 1, and a 1937-bp genomic deletion. The deletion included the entire
      exon 17, which was flanked by two Alu elements in introns 16 and 17. None of the
      mutations was found in 100 control chromosomes. In patient 5, no mutation was
      found by the exon sequencing analysis. Furthermore, expression level or
      nucleotide sequences of ALDH7A1 mRNA in lymphoblasts were normal. Plasma
      pipecolic acid concentration was not elevated in patient 5. These observations
      suggest that ALDH7A1 mutation is unlikely to be responsible for patient 5.
      Abnormal metabolism of GABA/glutamate in brain has long been suggested as the
      underlying pathophysiology of PDS. CSF glutamate concentration was elevated
      during the off-pyridoxine period in patient 3, but not in patient 2 or 5. These
      results suggest allelic and non-allelic heterogeneities of PDS, and that the CSF
      glutamate elevation does not directly correlate with the presence of ALDH7A1
      mutations.

PMID- 17433749
TI  - Evidence for function of UDP galactose pyrophosphorylase in mice with absent
      galactose-1-phosphate uridyltransferase.
AB  - Mice with deletion of the galactose-1-phosphate uridyltransferase (GALT) gene
      were examined for their ability to form (13)C labeled hepatic UDP glucose from
      administered 1-(13)C galactose. NMR analysis of urinary acetaminophen
      glucuronide, which is derived from hepatic UDP glucose showed (13)C enrichment
      after concomitant administration of (13)C galactose and acetaminophen. The
      finding is consistent with the function of UDP galactose pyrophosphorylase as an
      alternate pathway of galactose metabolism.

PMID- 17433750
TI  - Cryptic disease in a cat with painful and swollen hocks: an exercise in
      diagnostic reasoning and clinical decision-making.

PMID- 17433751
TI  - Dedicated MRI systems for rheumatology.

PMID- 17433752
TI  - Septic arthritis due to extended spectrum beta lactamase producing Klebsiella
      pneumoniae.
AB  - CASE REPORT: Septic arthritis due to Klebsiella species is a rare but serious
      infection that may destroy a joint and cause serious immobility. This is a report
      of two immunocompromised adult patients presenting with acute septic arthritis
      due to extended spectrum beta lactamase producing Klebsiella pneumoniae. The
      infection was treated successfully with a course of meropenem and amikacin in
      combination with early arthroscopic washout of the joint. Little information has
      been published on the management of this infection. We are therefore presenting a
      systematic literature review summarizing risk factors, clinical presentation,
      laboratory diagnosis, treatment regimens and outcome of this condition.
      DISCUSSION: On the basis of our study, we recommend an early diagnostic
      arthrocentesis of the joint for Gram stain microscopy, culture and antibiotic
      sensitivity testing to guide the appropriate use of antibiotics. In cases of
      hospital acquired infections where drug resistant Gram negative bacteria are
      suspected or prevalent, broad-spectrum antibiotics such as meropenem plus or
      minus amikacin may be given as the empirical treatment until the sensitivities
      are confirmed. In addition, adequate surgical joint lavage should be considered
      as the mainstay of treatment.

PMID- 17433753
TI  - A founding LRRK2 haplotype shared by Tunisian, US, European and Middle Eastern
      families with Parkinson's disease.
AB  - The Leucine-rich repeat kinase 2 (LRRK2) gene has been identified as a disease
      susceptibility gene for Parkinson's disease (PD), with G2019 (6055G>A) being the
      most frequent mutation. This mutation was present in 42% (38/91) of Tunisian
      families and 2% (1/39) of US families we have studied. A founding haplotype was
      identified in our data and it is shared by families from Tunisia, US, European
      and Middle Eastern countries. The most recent common founder of the mutation was
      dated to 2600 (95% CI: 1950-3850) years ago although additional studies are
      warranted to ensure an accurate age estimate for this mutation.

PMID- 17433754
TI  - Dopa-responsive camptocormia in a patient with multiple system atrophy.
AB  - Camptocormia in parkinsonism is defined by marked anteroflexion of the trunk,
      which is relieved by lying down together with minimal or no response to levodopa.
      We describe here a 47-year-old patient with multiple system atrophy with
      predominant parkinsonism associated with camptocormia; the camptocormia and
      parkinsonian motor symptoms were markedly improved with levodopa treatment.

PMID- 17433755
TI  - Is the rural idyll bad for your health? Stigma and exclusion in the English
      countryside.
AB  - The aim of this paper is to challenge assumptions that life in the English
      countryside is a healthy existence. This paper proposes that public health
      practitioners should consider the problems of stigma and social exclusion
      sometimes faced by individuals in rural areas. Using ethnographic research from a
      village in South East England the experiences of several individuals are examined
      to illustrate how stigma impacts on the health and well-being of those supposedly
      living in the rural idyll. It also argues for more ethnographic research to be
      conducted in health studies, particularly in rural areas, to gain deeper insight
      into health experiences.

PMID- 17433756
TI  - Postural taping decreases thoracic kyphosis but does not influence trunk muscle
      electromyographic activity or balance in women with osteoporosis.
AB  - BACKGROUND: Greater thoracic kyphosis is associated with increased biomechanical
      loading of the spine which is potentially problematic in individuals with
      osteoporotic vertebral fractures. Conservative interventions that reduce thoracic
      kyphosis warrant further investigation. This study aimed to investigate the
      effects of therapeutic postural taping on thoracic posture. Secondary aims
      explored the effects of taping on trunk muscle activity and balance. METHODS:
      Fifteen women with osteoporotic vertebral fractures participated in this within
      participant design study. Three taping conditions were randomly applied:
      therapeutic taping, control taping and no taping. Angle of thoracic kyphosis was
      measured after each condition. Force plate-derived balance parameters and trunk
      muscle electromyographic activity (EMG) were recorded during three static
      standing tasks of 40s duration. RESULTS: There was a significant main effect of
      postural taping on thoracic kyphosis (p=0.026), with a greater reduction in
      thoracic kyphosis after taping compared with both control tape and no tape. There
      were no effects of taping on EMG or balance parameters. CONCLUSIONS: The results
      of this study demonstrate that the application of postural therapeutic tape in a
      population with osteoporotic vertebral fractures induced an immediate reduction
      in thoracic kyphosis. Further research is needed to investigate the underlying
      mechanisms associated with this decrease in kyphosis.

PMID- 17433757
TI  - Structure, function and modulation of retinoic acid receptor beta, a tumor
      suppressor.
AB  - Only one of the three-retinoic acid receptors, RARbeta, is frequently deleted or
      epigenetically silenced at early stages in tumor progression and there is
      compelling evidence that RARbeta corresponds to a tumor suppressor. Recent
      discoveries may help to reveal the molecular basis of the tumor suppressive
      action of this retinoic acid receptor subtype and provide new tools for its
      analysis and, possibly, therapeutic exploitation. The first concerns the recent
      elucidation of the crystal structure of the ligand-binding domain of the agonist
      bound receptor. The second is the discovery of selective agonists, including
      isoform selective ligands, which are important tools to facilitate the
      pharmacological analysis of the tumor suppressor function of this protein in
      vivo. Lastly, its involvement in a retinoic acid-induced tumor-specific apoptosis
      program mediated by tumor necrosis factor-related apoptosis-inducing ligand
      (TRAIL). Herein we describe the structure, function and ligand-dependent
      transcription mechanism of retinoic acid receptor beta, and use rational drug
      design to understand the selectivity of these modulators.

PMID- 17433758
TI  - Involvement of the ERK/MAP kinase signalling pathway in milli-calpain activation
      and myogenic cell migration.
AB  - Recent research carried out in our laboratory has shown that IGF-1, TGF-beta1,
      and insulin were able to strongly stimulate myoblast migration by increasing
      milli-calpain expression and activity. However, the signalling pathways involved
      in these phenomena remain unknown. The aim of this study was to identify the
      signalling pathway(s) responsible for the effects of IGF-1, TGF-beta1, and
      insulin on myoblast migration and on milli-calpain expression and activity. For
      this purpose, wound healing assays were carried out in the presence of growth
      factors with or without specific inhibitors of ERK/MAP kinase and PI3K/Akt
      pathways. The results clearly showed that the inhibition of the ERK/MAP kinase
      pathway prevents the effects of growth factors on myoblast migration. Secondly,
      the expression and the activity of milli-calpain were studied in cells treated
      with growth factor, alone or with ERK/MAP kinase inhibitor. The results
      demonstrated that the up-regulation of milli-calpain expression and activity was
      mediated by the ERK/MAP kinase pathway. Finally, the possible implication of MyoD
      and myogenin, myogenic regulatory factors able to regulate milli-calpain
      expression, was studied. Taken together our results clearly showed that the
      ERK/MAP kinase signalling pathway is responsible for the effects of the three
      growth factors on myoblast migration and on milli-calpain expression and
      activity. On the opposite, the PI3K/Akt signalling pathway, MyoD and myogenin
      seem to be not implicated in these phenomena.

PMID- 17433759
TI  - DNA methylation profiling of transcription factor genes in normal lymphocyte
      development and lymphomas.
AB  - Transcription factors play a crucial role during hematopoiesis by orchestrating
      lineage commitment and determining cellular fate. Although tight regulation of
      transcription factor expression appears to be essential, little is known about
      the epigenetic mechanisms involved in transcription factor gene regulation. We
      have analyzed DNA methylation profiles of 13 key transcription factor genes in
      primary cells of the hematopoietic cascade, lymphoma cell lines and lymph node
      biopsies of diffuse large B-cell- and T-cell-non-Hodgkin lymphoma patients.
      Several of the transcription factor genes (SPI1, GATA3, TCF-7, Etv5, c-maf and
      TBX21) are differentially methylated in specific cell lineages and stages of the
      hematopoietic cascade. For some genes, such as SPI1, Etv5 and Eomes, we found an
      inverse correlation between the methylation of the 5' untranslated region and
      expression of the associated gene suggesting that these genes are regulated by
      DNA methylation. Differential methylation is not limited to cells of the healthy
      hematopoietic cascade, as we observed aberrant methylation of c-maf, TCF7, Eomes
      and SPI1 in diffuse large B-cell lymphomas. Our results suggest that epigenetic
      remodelling of transcription factor genes is a frequent mechanism during
      hematopoietic development. Aberrant methylation of transcription factor genes is
      frequently observed in diffuse large B-cell lymphomas and might have a functional
      role during tumorigenesis.

PMID- 17433760
TI  - Classification of hemodynamics from dynamic-susceptibility-contrast magnetic
      resonance (DSC-MR) brain images using noiseless independent factor analysis.
AB  - Dynamic-susceptibility-contrast (DSC) magnetic resonance imaging records signal
      changes on images when the injected contrast-agent particles pass through a human
      brain. The temporal signal changes on different brain tissues manifest distinct
      blood-supply patterns which are vital for the profound analysis of cerebral
      hemodynamics. Under the assumption of the spatial independence among these
      patterns, noiseless independent factor analysis (IFA) was first applied to
      decompose the DSC-MR data into different independent-factor images with
      corresponding signal-time curves. A major tissue type, such as artery, gray
      matter, white matter, vein, sinus, and choroid plexus, etc., on each independent
      factor image was further segmented out by an optimal threshold. Based on the
      averaged signal-time curve on the arterial area, the cerebral hemodynamic
      parameters, such as relative cerebral blood volume (rCBV), relative cerebral
      blood flow (rCBF), and mean transit time (MTT), were computed and their averaged
      ratios between gray matter and white matter for normal subjects were in good
      agreement with those in the literature. Data of a stenosis patient before and
      after treatment were analyzed and the result illustrates that this method is
      effective in extracting spatiotemporal blood-supply patterns which improves
      differentiation of pathological and non-pathological hemodynamics.

PMID- 17433761
TI  - The pathogen reduction treatment of platelets with S-59 HCl (Amotosalen) plus
      ultraviolet A light: genotoxicity profile and hazard assessment.
AB  - Despite restrictive donor criteria and screening procedures, infections resulting
      from the transfusion of bacterially contaminated platelet products continue to
      occur. Pathogen reduction technologies targeting nucleic acids have been
      developed. However, concerns about the safety of these procedures exist; the main
      concern being the possible mutagenic and carcinogenic effects of the pathogen
      inactivated preparation in the recipient. This report reviews the genotoxicity
      profile of the S-59 (Amotosalen) plus long wavelength ultraviolet light (UVA)
      pathogen reduction technology, and assesses the mutagenic and carcinogenic
      hazards in recipients of treated platelets. S-59, a synthetic heterocyclic
      psoralen, non-covalently intercalates into the nucleic acids of pathogens and
      forms crosslinks when UVA photoactivated. Before clinical use, the levels of
      residual S-59 and free photoproducts are greatly reduced using a 'compound
      adsorption device' (CAD). In vitro, S-59 is mutagenic in Salmonella typhimurium
      and mouse lymphoma L5178Y TK(+/-) cells, and is clastogenic in CHO cells. There
      is reduced activity (Salmonella, CHO cells) or no activity (mouse lymphoma cells)
      with metabolic activation (S9 mix). When tested up to toxic dose levels, S-59 was
      negative in the mouse bone marrow micronucleus assay and the rat hepatocyte
      unscheduled DNA synthesis (UDS) test. Based on comparative studies conducted with
      S-59 plus UVA-treated platelets (up to 25 times without CAD), any genotoxic
      effects can be attributed to residual S-59. Considering (1) the known genotoxic
      mechanism of action for S-59, (2) the negative in vivo studies for S-59 at
      multiples >40,000x over clinical peak plasma levels, and (3) the fact that the
      positive in vitro genotoxicity effects for the end product seem due to residual S
      59, any mutagenic hazard to a recipient of S-59 plus UVA-treated platelets is
      negligible and there is no concern about a carcinogenic potential as a
      consequence of a mutagenic activity. This conclusion is supported by a negative
      p53(+/-) mouse carcinogenicity study.

PMID- 17433762
TI  - Preparation, properties and infrared spectral studies of N-(p
      ethylphenyl)thiobenzohydroxamic acid.
AB  - The preparation of N-(p-ethylphenyl)thiobenzohydroxamic acid and its spectral
      properties are described in this paper. The preferred conformation of the acid is
      investigated by both infrared techniques and theoretical calculations at the DFT
      level. It is found that the acid exists in the cis thione (Z) form, rather than
      the trans form (E) in the gas phase. Both infrared spectroscopy and theoretical
      calculations show that this structure is stabilized by intramolecular hydrogen
      bonding.

PMID- 17433763
TI  - Laser-diode-excited intense luminescence and green-upconversion in erbium-doped
      bismuth-germanate-lead glasses.
AB  - We investigate the spectroscopic properties of the 1.5-microm emission from the
      (4)I(13/2)-->(4)I(15/2) transition of Er(3+) ions in bismuth-germanate-lead
      glasses for applications in broadband fiber amplifiers. The emission peak locates
      at 1532nm with a full width at half-maximum (FWHM) of approximately 65nm. The
      measured lifetime and the calculated emission cross-section of this transition
      are 3.3ms and 8.66x10(-21)cm(2), respectively. IR-to-green-upconversion occurs
      simultaneously upon excitation of the 1.5-microm emission with a commercially
      available 980nm laser diode. Effects of PbF(2) content on the thermal stability,
      structure and spectroscopic properties of Er(3+)-doped bismuth-germanate-lead
      glasses have been examined. We find that the substitution with PbF(2) provides a
      couple of potentials: shortening the UV cutoff band and decreasing the phonon
      energy of host glasses. Codoping of Yb(3+) significantly enhances both the green
      upconversion and 1.5-microm emission intensity by means of a nonradiative Yb(3+)-
      >Er(3+) energy transfer. Energy transfer processes and nonradiative phonon
      assisted decays could account for the population of the (2)H(11/2) level, which
      is an emitting level of the green-upconversion of Er(3+). The results indicate
      the possibility towards the development of bismuth-germanate-lead based glasses
      as photonics devices.

PMID- 17433764
TI  - Complexation study of brilliant cresyl blue with beta-cyclodextrin and its
      derivatives by UV-vis and fluorospectrometry.
AB  - The complexation reactions of brilliant cresyl blue (BCB) with beta-cyclodextrin
      (beta-CD), mono[2-O-(2-hydroxypropyl)]-beta-CD (2-HP-beta-CD), mono[2-O-(2
      hydroxyethyl)]-beta-CD (2-HE-beta-CD), and heptakis(2,6-di-methyl) -beta-CD (DM
      beta-CD) were investigated using UV-vis and fluorospectrometry. The complexation
      between BCB and CDs could inhibit the aggregation of BCB molecules and could
      cause its absorbance at 634nm gradually increasing. The fluorescence of BCB was
      also enhanced with the addition of CDs. The fluorescence enhancement was more
      notable in neutral and acidic media than in basic media. Hildebrand-Benesi
      equation was used to calculate the formation constants of beta-CDs with BCB based
      on the fluorescence differences in the CDs solution. The stoichiometry ratio was
      found to be 1:1. The complexing capacities of beta-CD and its three derivatives
      were compared and the results followed the order: 2-HP-beta-CD>2-HE-beta-CD>DM
      beta-CD>beta-CD. The effect of temperature on the formation of BCB-beta-CD
      inclusion complexes has also been examined. The results revealed that the
      formation constants decreased with the increase of temperature from 1038.9 to
      491.6l/mol. Enthalpy and entropy values were calculated and the values were 
      25.77kJ/mol and 35.04J/kmol, respectively. The thermodynamic measurements suggest
      that the inclusive process was enthalpic favor. The release of high-energy water
      molecules and Van der Waals force played an important role in the inclusive
      process.

PMID- 17433765
TI  - Ammonium dithionate- a new material for highly sensitive EPR dosimetry.
AB  - Polycrystalline ammonium dithionate has been examined for its radiation response
      in the low dose range (<5Gy) using EPR technique. The SO(3)(-) radical ion was
      detected as a single EPR line with a peak-to-peak derivative width of ca. 0.44mT
      in irradiated samples and its intensity was found to vary linearly with dose. At
      equal and moderate settings of microwave power and modulation amplitude ammonium
      dithionate was at least seven times more sensitive than l-alanine which is the
      most common EPR dosimeter standard. Pulse experiments were performed on the
      powder samples to obtain the longitudinal relaxation time. These and microwave
      saturation experiments served to indicate the optimal microwave power to be
      applied during measurements as an EPR dosimeter for best sensitivity of this
      material. It is thus claimed that ammonium dithionate has excellent potential to
      become an EPR dosimeter with a low limit of the measurable dose for cases where
      tissue equivalence is not required or can be corrected for.

PMID- 17433766
TI  - Density functional theory studies on tautomeric stability and infrared and Raman
      spectra of some purine derivatives.
AB  - The molecular vibrations of 6-hydroxy-purine (6HP) and 6-amino-purine (6AP) were
      investigated in polycrystalline sample, at room temperature by Fourier transform
      infrared (FTIR) and FT-Raman spectroscopy. The spectra of the above compounds
      have been recorded in the region 4000-50, 3500-100 cm(-1), respectively. They
      were interpreted with the aid of normal coordinate analysis following full
      structure optimization and force field calculations based on density functional
      theory (DFT) using HF/6-31G* and B3LYP/6-311+G** methods and basis set
      combinations. The results of the calculations were applied to simulated infrared
      and Raman spectra of the title compounds, which showed excellent agreement with
      the observed spectra. The dipole moment and the tautometric stability of purine
      derivatives were also studied.

PMID- 17433767
TI  - Conformational stability, structural parameters and vibrational assignment from
      variable temperature infrared spectra of krypton solutions and ab initio
      calculations of ethylisothiocyanate.
AB  - Variable temperature (-105 to -150 degrees C) studies of the infrared spectra
      (3500-400 cm(-1)) of ethylisothiocyanate, CH(3)CH(2)NCS, dissolved in liquid
      krypton have been recorded. Additionally the infrared spectra of the gas and
      solid have been re-investigated. These spectroscopic data indicate a single
      conformer in all physical states with a large number of molecules in the gas
      phase at ambient temperature in excited states of the CN torsional mode which has
      a very low barrier to conformational interchange. To aid in the analyses of the
      vibrational and rotational spectra, ab initio calculations have been carried out
      by the perturbation method to the second order (MP2) with valence and core
      electron correlation using a variety of basis sets up to 6-311+G(2df,2pd). With
      the smaller basis sets up to 6-311+G(d,p) and cc-PVDZ, the cis conformer is
      indicated as a transition state with all larger basis sets the cis conformer is
      the only stable form. The predicted energy difference from these calculations
      between the cis form and the higher energy trans conformer is about 125 cm(-1)
      which represents essentially the barrier to internal rotation of the NCS group
      (rotation around NC axis). Density functional theory calculation by the B3LYP
      method with the same basis sets predicts this barrier to be about 25 cm(-1). By
      utilizing the previously reported microwave rotational constants with the
      structural parameters predicted by the ab initio MP2(full)/6-311+G(d,p)
      calculations, adjusted r(0) structural parameters have been obtained for the cis
      form. The determined heavy atom parameters are: r(NC)=1.196(5), r(CS)=1.579(5),
      r(CN)=1.439(5), r(CC)=1.519(5)A for the distances and angles of
      angleCCN=112.1(5), angleCNC=146.2(5), angleNCS=174.0(5) degrees . The centrifugal
      distortion constants, dipole moments, conformational stability, vibrational
      frequencies, infrared intensities and Raman activities have been predicted from
      ab initio calculations and compared to experimental quantities when available.
      These results are compared to the corresponding quantities of some similar
      molecules.

PMID- 17433768
TI  - Dual fluorescence of N-phenylanthranilic acid: Effect of solvents, pH and beta
      cyclodextrin.
AB  - Spectral characteristics of N-phenylanthranilic acid (NPAA) have been studied in
      different solvents, pH and beta-cyclodextrin (beta-CD) and compared with
      anthranilic acid (2-aminobenzoic acid, 2ABA). In all solvents a dual fluorescence
      is observed in NPAA, whereas 2ABA gives single emission. Combining the results
      observed in the absorption, fluorescence emission and fluorescence excitation
      spectra, it is found that strong intramolecular hydrogen bonding (IHB)
      interactions present in NPAA molecule. The inclusion complex of NPAA with beta-CD
      is analysed by UV-vis, fluorimetry, FT-IR, (1)H NMR, scanning electron microscope
      and AM 1 method. The above spectral studies show that NPAA forms a 1:1 inclusion
      complex with beta-CD and COOH group present in the beta-CD cavity. A mechanism is
      proposed to explain the inclusion process.

PMID- 17433769
TI  - Vibrational spectra and fundamental structural assignments from HF and DFT
      calculations of methyl benzoate.
AB  - The Fourier transform Raman and Fourier transform infrared spectra of methyl
      benzoate (MB) were recorded in the liquid phase. The equilibrium geometry,
      harmonic vibrational frequencies, infrared intensities and Raman scattering
      activities, depolarization ratios, reduced masses were calculated by Hartree-Fock
      (HF) and density functional B3LYP method with the 6-311+G(d,p) basis set. The
      scaled theoretical wavenumbers showed very good agreement with the experimental
      values. The thermodynamic functions of the title compound were also performed at
      HF/6-311+G(d,p) and B3LYP/6-311+G(d,p) levels of theory. A detailed
      interpretations of the infrared and Raman spectra of methyl benzoate is reported.
      The theoretical spectrograms for FT-IR spectra of the title molecule have been
      constructed.

PMID- 17433770
TI  - Temperature sensing behaviour of the stark sublevels.
AB  - The temperature dependence of the fluorescence intensity ratio of the two stark
      components of (4)S(3/2)-->(4)I(15/2) transition using 800 nm radiation from a Ti
      sapphire laser pumped by the second harmonic of Nd:YVO(4) laser has been
      augmented in Er(3+) doped tellurite glass. It is emphasized that even the two
      stark components of (4)S(3/2)-->(4)I(15/2) transition may be utilized to monitor
      the temperature within 300-550 K with its appreciable sensitivity.

PMID- 17433771
TI  - IR, Raman and SERS spectra of disodium terephthalate.
AB  - The IR and Raman spectra of disodium terephthalate were recorded and analysed.
      Surface enhanced Raman scattering (SERS) spectrum was recorded in silver colloid.
      The vibrational wavenumber of the compound have been computed using the Hartree
      Fock/6-31G* basis and compared with the experimental values. SERS studies suggest
      a flat orientation of the molecule at the metal surface.

PMID- 17433772
TI  - Steroidogenic acute regulatory protein (StAR), a novel mitochondrial cholesterol
      transporter.
AB  - Cholesterol is a vital component of cellular membranes, and is the substrate for
      biosynthesis of steroids, oxysterols and bile acids. The mechanisms directing the
      intracellular trafficking of this nearly insoluble molecule have received
      increased attention through the discovery of the steroidogenic acute regulatory
      protein (StAR) and similar proteins containing StAR-related lipid transfer
      (START) domains. StAR can transfer cholesterol between synthetic liposomes in
      vitro, an activity which appears to correspond to the trans-cytoplasmic transport
      of cholesterol to mitochondria. However, trans-cytoplasmic cholesterol transport
      in vivo appears to involve the recently-described protein StarD4, which is
      expressed in most cells. Steroidogenic cells must also move large amounts of
      cholesterol from the outer mitochondrial membrane to the first steroidogenic
      enzyme, which lies on the matrix side of the inner membrane; this action requires
      StAR. Congenital lipoid adrenal hyperplasia, a rare and severe disorder of human
      steroidogenesis, results from mutations in StAR, providing a StAR knockout of
      nature that has provided key insights into its activity. Cell biology experiments
      show that StAR moves large amounts of cholesterol from the outer to inner
      mitochondrial membrane, but acts exclusively on the outer membrane. Biophysical
      data show that only the carboxyl-terminal alpha-helix of StAR interacts with the
      outer membrane. Spectroscopic data and molecular dynamics simulations show that
      StAR's interactions with protonated phospholipid head groups on the outer
      mitochondrial membrane induce a conformational change (molten globule transition)
      needed for StAR's activity. StAR appears to act in concert with the peripheral
      benzodiazepine receptor, but the precise itinerary of a cholesterol molecule
      entering the mitochondrion remains unclear.

PMID- 17433774
TI  - Validation of metabolic pathway databases based on chemical substructure search.
AB  - Metabolic pathway databases such as KEGG contain information on thousands of
      biochemical reactions drawn from the biomedical literature. Ensuring consistency
      of such large metabolic pathways is essential to their proper use. In this paper,
      we present a new method to determine consistency of an important class of
      biochemical reactions. Our method exploits the knowledge of the atomic
      rearrangement pattern in biochemical reactions, to reduce the automatic atom
      mapping problem to a series of chemical substructure searches between the
      substrate and the product of a biochemical reaction. As an illustrative
      application, we describe the exhaustive validation of a substantial portion from
      the latest release of the KEGG LIGAND database.

PMID- 17433775
TI  - Electromyography of the trunk and abdominal muscles in golfers with and without
      low back pain.
AB  - Twelve male golfers who experienced low back pain (LBP) whilst playing or
      practicing golf and 18 asymptomatic golfers were recruited and divided into
      handicap-specific groups; low-handicap golfers, with a handicap between 0 and 12
      strokes; and high-handicap golfers, with a handicap of between 13 and 29 strokes.
      The myoelectric activity of the lumbar erector spinae (ES) and the external
      obliques (EO) was recorded via surface electromyography (EMG), whilst the golfers
      performed 20 drives. The root mean square (RMS) was calculated for each subject
      and the data for the ES and EO were normalised to the EMGs recorded whilst
      holding a mass equal to 5% of the subjects' body mass at arms length and whilst
      performing a double-leg raise, respectively. The results showed that the low
      handicap LBP golfers tended to demonstrate reduced ES activity at the top of the
      backswing and at impact and greater EO activity throughout the swing. The high
      handicap LBP golfers demonstrated considerably more ES activity compared with
      their asymptomatic counterparts, whilst EO activity tended to be similar between
      the high-handicap groups. The reduced ES activity demonstrated by the low
      handicap LBP group may be associated with a reduced capacity to protect the spine
      and its surrounding structures at the top of the backswing and at impact, where
      the torsional loads are high. When considering this with the increased EO
      activity demonstrated by these golfers, it is reasonable to suggest that these
      golfers may be demonstrating characteristics/mechanisms that are responsible for
      or are a cause of LBP.

PMID- 17433776
TI  - Controlling fasciolosis in the Bolivian Altiplano.

PMID- 17433773
TI  - PPARs and molecular mechanisms of transrepression.
AB  - In the last few years, PPARs have emerged as key regulators of inflammatory and
      immune responses. However, the mechanistic basis of the anti-inflammatory effects
      of peroxisome proliferator-activated receptors (PPARs) remains poorly understood.
      Accumulating evidence suggests that these effects result from inhibition of
      signal-dependent transcription factors that mediate inflammatory programs of gene
      activation. Several mechanisms underlying negative regulation of gene expression
      by PPARs have been described. Recent studies, using siRNA, microarray analysis
      and macrophage-specific knockout mice, have highlighted PPARs molecular
      transrepression mechanism in macrophages. Identification of their mechanism of
      action should help promote the understanding of the physiologic roles that PPARs
      play in immunity and contribute to the development of new therapeutic agents.

PMID- 17433777
TI  - Introducing histone modification in trypanosomes.
AB  - Nuclear DNA is wrapped around histones. Vigorous research over the past decade
      has established a central role for histone post-translational modification in
      controlling the DNA-protein interactions that are required for successful growth
      and propagation. Recent work now provides a description of acetylated and
      methylated residues in the divergent trypanosome core histones. Future studies
      should provide insights into the genomic distribution of each modification and
      their roles in growth and pathogenesis.

PMID- 17433778
TI  - Differential gene expression between Mycobacterium bovis and Mycobacterium
      tuberculosis.
AB  - The high sequence identity among the Mycobacterium bovis and Mycobacterium
      tuberculosis genomes contrasts with the physiological differences reported
      between these pathogens, suggesting that variations in gene expression may be
      involved. In this study, microarray hybridization was used to compare the total
      transcriptome of M. bovis and M. tuberculosis, during the exponential phase of
      growth. Differential expression was detected in 258 genes, representing a 6% of
      the total genome. Variable genes were grouped according to functional categories.
      The main variations were found in genes encoding proteins involved in
      intermediary metabolism and respiration, cell wall processes, and hypothetical
      proteins. It is noteworthy that, compared to M. tuberculosis, the expression of a
      higher number of transcriptional regulators were detected in M. bovis. Likewise,
      in M. tuberculosis we found a higher expression of the PE/PPE genes, some of
      which code for cell wall related proteins. Also, in both pathogens we detected
      the expression of a number of genes not annotated in the M. tuberculosis H37Rv or
      M. bovis 2122 genomes, but annotated in the M. tuberculosis CDC1551 genome. Our
      results provide new evidence concerning differences in gene expression between
      both pathogens, and confirm previous hypotheses inferred from genome comparisons
      and proteome analysis. This study may shed some new light on our understanding of
      the mechanisms relating to differences in gene expression and pathogenicity in
      mycobacteria.

PMID- 17433779
TI  - Incidence, etiology, classification, and management of neuralgia after posterior
      lumbar interbody fusion surgery in 226 patients.
AB  - BACKGROUND CONTEXT: Neurological symptoms are a well-recognized complication
      after posterior lumbar interbody fusion (PLIF) surgery. Concerns about this
      potential problem may deter surgeons from performing the procedure. PURPOSE: To
      determine the incidence, etiology, prevention, and management of neuralgia after
      PLIF surgery. STUDY DESIGN/SETTING: This study is a retrospective review of
      patients who underwent PLIF surgery at a university hospital in the north east of
      England. PATIENT SAMPLE: Two hundred sixty patients who met the inclusion
      criteria of degenerative disc disease, spondylolisthesis, disc herniation, and
      postlaminectomy/postdiscectomy syndrome underwent PLIF surgery. OUTCOME MEASURES:
      The outcome measure of neuralgia was assessed postoperatively by a subjective
      description of leg pain. Patients were considered to have post PLIF neuralgia if
      they complained of severe radiculopathy, which was not present before surgery.
      METHODS: During the study period April 1996 to April 2002, all patients who met
      the inclusion criteria underwent the PLIF procedure. Outcome was assessed
      postoperatively. In all but the first 20 cases, interbody cages were used. A
      subtotal superior facetectomy was performed on the first 103 patients. The
      subsequent 123 patients had a total removal of the superior facet. Autogenous
      bone and pedicle screws and plates were used in all cases. RESULTS: The study
      group comprised 226 patients (121 women, 105 men; mean age at surgery, 44.1
      years; age range, 12-81 years). Duration of symptoms ranged from 5 to 480 months
      (mean, 90.6 months; median, 60.0). Overall, there were 16 cases of neuralgia in
      226 patients (7.1%). In the subtotal facetectomy group, 10 of the 103 patients
      (9.7%) had neuralgic symptoms. In the total facetectomy group, 6 of the 123
      patients (4.9%) had neuralgic symptoms. The difference in incidence was not
      statistically significant (p=.158). CONCLUSIONS: This study describes our
      experiences of post-PLIF neuralgia. It outlines strategies for prevention and
      management of the problem.

PMID- 17433780
TI  - Magnetic resonance imaging showed no signs of overuse or permanent injury to the
      lumbar sacral spine during a Special Forces training course.
AB  - BACKGROUND CONTEXT: Special Forces training is even more demanding than that of
      elite athletes. The training includes grueling physical activity and periods of
      sleep deprivation. The soldiers routinely carry heavy loads up to 40% of their
      body weight on their backs while running and marching for distances up to 90 km.
      PURPOSE: Our purpose was to find out if Special Forces recruits are able to
      complete the preparatory Navy Seals training program without sustaining magnetic
      resonance imaging (MRI) signs of overuse or irreversible injury to their backs.
      STUDY DESIGN/SETTING: Prospective cohort study. We performed MRI scans before and
      after 14 weeks of Navy Seals preparatory training course. PATIENT SAMPLE: Ten
      soldiers underwent MRI of their lumbar sacral spines and right knees before and
      after the completion of Navy Seals preparatory training. OUTCOME MEASURES:
      Physiologic measures. Lumbar sacral spine and knee MRI tests were performed
      before and after the training to identify changes in the spinal discs, facet
      joints, pars interarticularis, vertebral bodies, knee articular cartilage,
      ligaments, knee menisci, and the presence or absence of soft tissue and/or bone
      edema. METHODS: We investigated the difference in spine and knee pathology before
      and after a 14-week Navy Seals preparatory training course by using MRI criteria.
      The recruits participating in the study were monitored for acute and overuse
      injuries every 3 to 4 weeks. RESULTS: Before the training, seven out of ten spine
      MRI scans were normal. Two showed small L5-S1 disc bulges, one of them with
      concomitant Scheuermann's disease. Another soldier's MRI showed L1-L4 mild
      Scheuermann's disease. Follow-up MRI showed no spinal changes. Before the
      training, one knee had a small lateral femoral condyle cartilage lesion. Nine of
      ten knees had prepatellar swelling, five had increased joint fluid, and two bone
      edema. Follow-up magnetic resonance imaging showed improvement in the prepatellar
      swelling in eight soldiers, no change in one soldier, and increased knee effusion
      and a new medial femoral condyle bone edema in another. The lateral femoral
      condyle lesion remained unchanged. CONCLUSIONS: According to MRI criteria, the
      soldiers in this study completed the 14-week training, which involved loading of
      their spines far beyond the levels recommended by the US National Institute for
      Occupational Safety and Health without sustaining irreversible damage to their
      spines or knees. Although the subjects' knees showed signs of overuse injury,
      their backs did not.

PMID- 17433781
TI  - Prospective analysis of clinical evaluation and self-assessment by patients after
      decompression surgery for degenerative lumbar canal stenosis.
AB  - BACKGROUND CONTEXT: Objective measures including neurological findings,
      radiographic evaluation, and the Japanese Orthopaedic Association (JOA) score are
      commonly used for the evaluation of surgical outcomes. Because many surgeries are
      performed primarily to improve quality of life, a patient's subjective
      evaluations are also important for accurately assessing surgical outcomes.
      Currently available instruments for assessing quality of life include the Short
      Form 36 (F-36), the Oswestry disability index (ODI), and the visual analog scale
      (VAS) clinical pain scale. PURPOSE: The aims of this study were to measure
      surgical outcomes by using both objective measures and subjective measures
      including patient self-assessments and psychological changes; to assess the
      adequacy of the JOA alone for measuring outcome; and to determine which measures,
      the SF-36v2, ODI, VAS, or JOA correlate with the VAS pain scale score in lumbar
      canal stenosis. STUDY DESIGN: We performed a prospective study to measure
      surgical outcomes for lumbar canal stenosis using traditional objective measures
      such as neurological findings and subjective measures such as performance of
      ADLs, patient self-assessments, and psychological changes. PATIENT SAMPLE: Forty
      two surgical patients with a mean age of 66.8+/-10.9 years at the time of surgery
      were included in the study. All cases were followed for more than 2 years.
      Surgical indications included no response to conservative treatment and
      neurological deterioration. Neurological symptoms were classified as nerve root
      type, cauda equine type, or combined type. We performed surgical decompression at
      the location of the dural or root indentation by myelography. The concomitant
      diagnosis causing the spinal stenosis was degenerative spondylolisthesis in 20
      cases undergoing posterolateral fusion with pedicle screws. OUTCOME MEASURES:
      Surgical outcomes were assessed by comparing preoperative and 24-month
      postoperative JOA scores for low back pain, SF-36v2, ODI-v2, and VAS scores.
      Statistical analysis was performed by using the analysis of variance. A p
      value<0.05 was considered statistically significant. METHODS: Objective clinical
      measures, patient self-assessments, and psychological changes were measured
      before and at 24 months postoperatively. We also examined which measurements
      correlated with the VAS scale for pain evaluation, thereby relating patient
      satisfaction to surgery outcome. RESULTS: All JOA, SF-36v2, ODI-v2, and VAS
      scores significantly improved postoperatively. The physical component summary
      (PCS) of the SF-36 v2 showed significant improvement, although all scores
      remained less than the Japanese norm-based scores (NBSs). The mental component
      summary (MCS) exhibited such a significant improvement that all postoperative
      subscales were higher than the Japanese NBS. JOA scores significantly correlated
      only with postoperative lower-extremity VAS score. All PCS and two MCS scores
      significantly correlated with the VAS score for low back pain. Parts of the PCS
      and MCS significantly correlated with the lower-extremity VAS. The ODI
      significantly correlated with both the preoperative and postoperative VAS scores
      for low back pain as well as with the postoperative lower-extremity VAS score.
      CONCLUSIONS: The JOA, SF-36, ODI, and VAS questionnaires are all useful
      instruments for measuring surgical outcomes. The VAS score is a better assessment
      of physical rather than mental health. The ODI is more reflective of patients'
      subjective symptoms. Finally, the SF-36 is particularly informative because it
      includes questions addressing both psychological and physical status. Therefore,
      when combined, the SF-36v2, VAS, and ODI scores are a valuable complement to the
      JOA scores in evaluating outcomes of surgery for lumbar canal stenosis.

PMID- 17433782
TI  - Leptin expression by annulus cells in the human intervertebral disc.
AB  - BACKGROUND CONTEXT: It is now known that leptin acts not only as a metabolic
      signal related to energy homeostasis but also as an endocrine hormone regulating
      traditional endocrine systems and neuroendocrine function in various cells. It
      participates in bone remodeling and acts as a growth factor stimulating
      proliferation. Expression of leptin and the presence of leptin receptors have not
      been explored in disc tissue. PURPOSE: To determine (1) whether leptin is
      produced by cells in the human annulus in vivo, (2) whether annulus cells have
      leptin receptors in vivo and in vitro, and (3) whether measurable amounts of
      leptin are produced during three-dimensional culture of human annulus cells.
      STUDY DESIGN/SETTING: Studies were approved by the human subjects Institutional
      Review Board. Surgical and donor disc tissue was obtained and assessed by using
      immunocytochemistry of paraffin-embedded disc tissue. Annulus cells were also
      cultured from disc specimens and conditioned media assessed for the production of
      leptin during three-dimensional culture. PATIENT SAMPLE: Disc tissue was examined
      from 7 young subjects and 29 adult subjects. OUTCOME MEASURES: Immunodetection of
      leptin and leptin receptors in cells of the human annulus; conditioned media was
      analyzed for production of leptin in vitro by human disc cells. METHODS: Human
      annulus tissue and cultured cells were examined by using immunohistochemical
      methods to identify the presence of leptin and leptin receptors. Human disc cells
      were assayed for leptin production in three-dimensional culture. RESULTS:
      Immunocytochemistry showed the presence of intracellular leptin and the presence
      of leptin receptors in some (but not all) annulus cells in the human disc.
      Production of leptin by annulus cells was further confirmed by assays of
      conditioned media from three-dimensional annulus cell culture. CONCLUSIONS: These
      novel studies identify the presence of a heretofore unrecognized cytokine/hormone
      and its receptor in human annulus cells. Because of the mitogenic role of leptin
      in other tissues, the present work points to the importance of future studies to
      explore whether leptin has a mitogenic function in maintaining disc cell numbers.

PMID- 17433783
TI  - Effects of copper and cadmium on cholinesterase and glutathione S-transferase
      activities of two marine gastropods (Monodonta lineata and Nucella lapillus).
AB  - With the view of using Nucella lapillus and Monodonta lineata as bioindicators in
      biomonitoring programs in the NW coast of Portugal, the sensitivity to copper and
      cadmium of these two common species in Atlantic coasts of Europe was
      investigated. Assays based on mortality and on the activity of the enzymes
      cholinesterases (ChE) and glutathione S-transferases (GST) were used, as these
      biomarkers have been used in biomonitoring studies in the area. ChEs present in
      foot muscle of both species were characterised and found to show properties of
      both typical acetylcholinesterase and pseudocholinesterase. Cadmium LC50s for N.
      lapillus and M. lineata were 2.64 and 2.44 mg/L, respectively, while the lowest
      observed effect concentration (LOEC) was 1.53 mg/L for both species. LOEC value
      for cooper was 0.075 mg/L for both. Cadmium in vivo exposure increased ChE
      activity of N. lapillus, but had no effects on M. lineata ChE. No in vitro
      effects of cadmium on ChE activity of any of the tested species was observed.
      Copper had no significant in vivo effects on ChE activity, although it inhibited
      the ChE of both species in vitro, the IC50s being 5.87 and 12.17 mg/L for N.
      lapillus and M. lineata, respectively. Cadmium had no significant effects on GST
      activity of either species, while copper caused a significant reduction of N.
      lapillus GST (LOEC=0.044 mg/L) but had no effect on M. lineata GST. Results
      indicate that (i) N. lapillus and M. lineata have a similar acute sensitivity to
      cadmium and copper; (ii) ChE and GST of these species are sensitive to cadmium
      (iii) ChEs of both species are inhibited by copper at concentrations in the mg/L
      range and therefore, its use is limited to heavily polluted sites; (iv) N.
      lapillus GST does not seem to be a suitable biomarker for copper, at least in the
      range of concentrations tested, since it was inhibited by copper, but no clear
      concentration-response relationship was observed.

PMID- 17433784
TI  - Cd/Zn exposure interactions on metallothionein response in Eisenia fetida
      (Annelida, Oligochaeta).
AB  - We studied metallothionein (MT) response in the manure worm Eisenia fetida after
      exposures to cadmium (Cd), zinc (Zn) or cadmium and zinc spiked media. MT was
      studied both at the protein level by Dot Immunobinding Assay, (DIA) and at the
      expression level by Northern blotting. Cd was highly accumulated by worms whereas
      Zn body concentration was regulated. In addition, Zn would limit Cd accumulation
      in worms exposed to low Cd concentrations (1 and 8 mg Cd kg(-1) of dry soil).
      Exposure to a mixture of Cd and Zn at high concentrations increased cytosolic MT
      levels. This increase would allow worms to regulate body Zn concentrations and
      also to limit Cd toxicity. Cd exposures increased gene expression of Cd-binding
      MT isoform (MT 2A) whereas Zn did not. However, when both metals were at high
      concentrations in the exposure medium, this expression was further increased.
      Several hypotheses are proposed to explain the results and the best approach to
      estimate metal exposure of this earthworm species is given. Further experiments
      have now to be performed to evaluate the usefulness of these MT responses for
      field contaminated soils toxicity assessment using this earthworm species.

PMID- 17433785
TI  - Short telomeres limit tumor progression in vivo by inducing senescence.
AB  - Telomere maintenance is critical for cancer progression. To examine mechanisms of
      tumor suppression induced by short telomeres, we crossed mice deficient for the
      RNA component of telomerase, mTR(-/-), with Emu-myc transgenic mice, an
      established model of Burkitt's lymphoma. Short telomeres suppressed tumor
      formation in Emu-myc transgenic animals. Expression of Bcl2 blocked apoptosis in
      tumor cells, but surprisingly, mice with short telomeres were still resistant to
      tumor formation. Staining for markers of cellular senescence showed that pretumor
      cells induced senescence in response to short telomeres. Loss of p53 abrogated
      the short telomere response. This study provides in vivo evidence for the
      existence of a p53-mediated senescence mechanism in response to short telomeres
      that suppresses tumorigenesis.

PMID- 17433786
TI  - Oxidized low density lipoprotein receptor-1 mediates oxidized low density
      lipoprotein-induced apoptosis in human umbilical vein endothelial cells: role of
      reactive oxygen species.
AB  - Studies have shown that oxidized low density lipoprotein (ox-LDL) elicits both
      necrotic and apoptotic cell death and several mechanisms have been proposed. Ox
      LDL induces reactive oxygen species (ROS), a second messenger that might be
      involved in apoptosis, formation in different types of cells including
      endothelial cells (ECs) and smooth muscle cells (SMCs). As lectin-like ox-LDL
      receptor-1 (LOX-1) was the main receptor for ox-LDL, this study was designed to
      determine whether the apoptosis induced by ox-LDL was mediated by LOX-1 in
      cultured human umbilical vein endothelial cells (HUVECs) and whether there is an
      association between LOX-1 mediated apoptosis and the production of ROS. After
      exposure to ox-LDL (50,100, and 150 microg/ml for 18 h), HUVECs exhibit typical
      apoptotic characteristics as determined by transmission electron microscopy and
      flow cytometry analysis in a dose-dependent pattern. Ox-LDL increases
      intracellular ROS formation including superoxide anion (O2-) and hydrogen
      peroxide (H2O2) in a dose-dependent and time-dependent manner. Pretreatment with
      anti-LOX-1 mAb, Vitamin C, apocynin or catalase significantly reduced ROS
      production and prevented ox-LDL-induced apoptosis, while indomethacin or
      allopurinol had no effect. These results suggest that LOX-1 mediates ox-LDL
      induced apoptosis in endothelial cells and that ROS production and NADPH oxidase
      might play an important role in ox-LDL-induced apoptosis.

PMID- 17433787
TI  - A critical evaluation of serologic markers for inflammatory bowel disease.

PMID- 17433788
TI  - Aberrant crypt foci: what we know and what we need to know.
AB  - Aberrant crypt foci (ACF) have emerged as a putative precursor to colorectal
      adenomas and are a potential biomarker for colorectal carcinoma. In this review,
      we describe the histologic and endoscopic characteristics of human ACF, summarize
      the identified genetic abnormalities, and examine the evidence for using ACF as a
      biomarker for colorectal carcinoma. The published literature on aberrant crypt
      foci was identified using a MEDLINE/PubMed search with a secondary review of
      cited publications. Epidemiologic studies support a role for ACF in the adenoma
      carcinoma sequence. Genetic abnormalities that occur in and are characteristic of
      colorectal carcinoma have been described in ACF. Although chromoendoscopy with
      magnification colonoscopy can identify human ACF in vivo, standardization of the
      definition and of the technique for endoscopic identification and classification
      is needed. Studies of reproducibility, interobserver variability, and continuity
      over time to validate ACF as a clinical end point are required. ACF hold promise
      as a biomarker for colorectal carcinoma, but additional study is needed.

PMID- 17433789
TI  - Colonic amyloidosis.

PMID- 17433790
TI  - Percutaneous endoscopic jejunostomy feeding tube "knot" working: a rare
      complication.

PMID- 17433791
TI  - Patient recruitment into a randomised controlled trial of supervised exercise
      therapy in sedentary women treated for breast cancer.
AB  - BACKGROUND: The purpose of this study was to determine the effectiveness of
      different recruitment strategies used to recruit patients into the Sheffield
      Exercise and Breast Cancer Trial (SHERBERT), which involved exercise as a
      therapy, in sedentary women treated for breast cancer. We also evaluated whether
      the routes of recruitment distinguished patients participating in the trial in
      terms of socio-economic characteristics, lifestyle behaviours, cancer
      treatment(s), treatment side effects, length of treatment and time since
      treatment was completed. METHODS: SHERBERT aimed to recruit at least 114
      sedentary women, aged 18-65 years, who had been treated for breast cancer between
      1 and 3 years previously, to receive exercise therapy, an equal contact exercise
      placebo intervention or usual care. Potentially eligible patients were recruited
      by postal invitation letters from their treating clinician (i.e.
      oncologist/surgeon) or by a range of community strategies. RESULTS: We identified
      572 potentially eligible patients via our various recruitment strategies. The
      response rate to clinician invitation letters was 39.3% (N=148/377), of patients
      who responded and remained available and interested (N=112) 46.4% (N=52) were
      eligible to be randomised. The community strategies derived a total of 195
      interested responses, of these 66 patients (33.8%) were eligible to be
      randomised. On the basis of recruitment via clinician invitation letter we
      estimated the trial recruitment rate amongst eligible patients to be 28.6%. A
      total of 108 patients were eventually randomised. Responders to clinician
      invitation letters were more affluent compared to non-responders. Randomised
      patients recruited via different strategies did not vary significantly in terms
      of their socio-economic characteristics, lifestyle behaviours or variables
      related to cancer treatment. CONCLUSIONS: The number of patients randomised was
      marginally lower than anticipated. We were able to identify and highlight
      valuable information for planning the recruitment of future trials involving
      similar populations.

PMID- 17433792
TI  - A tolloid homologue from the Pacific oyster Crassostrea gigas.
AB  - The genes governing mesoderm specification have been extensively studied in
      vertebrates, arthropods and nematodes. The latter two phyla belong to the
      Ecdysozoan clade but little is understood of the role that these genes might play
      in the development of the other major protostomal clade, the Lophotrochozoa. As
      part of a wider project to analyze the functions associated with transforming
      growth factor beta superfamily members in Lophotrochozoa, we have cloned a gene
      encoding a tolloid homologue from the bivalve mollusc Crassostrea gigas. Tolloid
      is a key developmental protein that regulates the activity of bone morphogenetic
      proteins (BMPs). We have determined the intron-exon structure of the gene
      encoding C. gigas tolloid and have compared it with those of homologous genes
      from both protostomes and deuterostomes. In order to analyze the functionality of
      oyster tolloid the zebrafish embryo has been employed as a reporter organism and
      we show that over-expression of this protein results in the ventralization of
      zebrafish embryos at 24h post fertilization. The expression of the C. gigas
      tolloid gene during embryonic and larval development as well as in adult tissues
      is also explored.

PMID- 17433793
TI  - Ion and liquid transport across the bronchiolar epithelium.
AB  - The proper homeostasis of the airway surface liquid (ASL) depends on
      transepithelial ion and fluid transport and is critically important for lung
      defence, and more specifically for mucociliary transport. In cystic fibrosis
      (CF), abnormal ion and fluid transport lead to depleted ASL volume resulting in
      mucus plugs and recurrent lung infections. Like bronchi, human bronchioles
      exhibit amiloride-sensitive Na(+) absorption and cyclic-AMP and Ca(2+)-activated
      Cl(-) secretion. However, cyclic-AMP-stimulated Cl(-) and fluid secretion appears
      to be quantitatively more important in bronchioles than in bronchi. In CF
      bronchioles, like in CF bronchi, the ASL height is reduced because of an
      abnormally persistent Na(+) absorption, combined with a lacking CFTR-dependent
      Cl(-) secretion. The precocity and severity of the bronchiolar disease in CF
      could be attributed in part to the more important role of CFTR-dependent Cl(-)
      secretion and fluid secretion, and the lack of compensatory ATP-driven Cl(-)
      secretion and fluid secretion, in bronchioles compared to bronchi.

PMID- 17433794
TI  - Use of alternative and complementary therapies by inflammatory bowel disease
      patients in an Italian tertiary referral centre.
AB  - BACKGROUND: Alternative and complementary therapies are increasingly used by
      patients with inflammatory bowel disease, but no data are available on their use
      in Italy. AIM: To ascertain the prevalence and pattern of the use of alternative
      and complementary therapies, and demographic and clinical factors associated with
      their use in a large sample of Italian inflammatory bowel disease patients.
      METHODS: A structured questionnaire was administered to a cohort of outpatients
      at a tertiary referral centre. RESULTS: Five hundred and fifty-two patients
      completed the questionnaire; 156 (28%) reported using alternative and
      complementary therapies, which mainly involved homeopathy (43.6%), followed by
      controlled diets or dietary supplements (35.5%), herbs (28.2%), exercise (25.6%)
      and prayer (14.7%). Alternative and complementary therapies were used to
      ameliorate intestinal symptoms (52.5%), in the hope of being cured (41%) and to
      reduce the intake of drugs (39.7%). An improvement in well-being (45.5%) and
      inflammatory bowel disease symptoms (40.3%) were the most commonly reported
      benefits. A higher education (p=0.027), a more frequently relapsing disease
      (p=0.001) and dissatisfaction with the doctor's communication (p=0.001)
      correlated with alternative and complementary therapy use. Non-compliance with
      conventional drugs, disease severity and curiosity regarding novel therapies were
      predictors of alternative and complementary therapy use. CONCLUSIONS: Alternative
      and complementary therapies are frequently used by Italian inflammatory bowel
      disease patients. Doctors should improve their empathy and their understanding
      about possible benefits of alternative and complementary therapies.

PMID- 17433795
TI  - Long-term endoscopic and clinical follow-up of untreated type 1 gastric
      neuroendocrine tumours.
AB  - BACKGROUND AND AIMS: Type 1 gastric neuroendocrine tumour surveillance and
      treatment are a matter of debate. Endoscopic, or surgical, resection and chronic
      somatostatin analog therapy have been proposed. Based on the favourable behaviour
      of this neoplasm, we performed an endoscopic and clinical follow-up in 11
      patients affected by type 1 gastric neuroendocrine tumours, avoiding any specific
      treatment. METHODS: Between 1994 and 2006, we prospectively recorded the data of
      11 untreated patients with type 1 gastric neuroendocrine tumours who underwent an
      endoscopic and clinical follow-up. All the patients were also evaluated by means
      of an abdominal computed tomography scan, somatostatin receptor scintigraphy and
      blood tests. RESULTS: During the follow-up (median 54 months, range 9-136), the
      endoscopic picture of 4 (36%) out of 11 patients changed in terms of increased
      number of lesions. In none of the cases were detected any lesions that exceeded
      10mm in diameter, and none of the patients demonstrated any evidence of local or
      distant metastases. CONCLUSIONS: Our data confirm the literature data of the
      indolent behaviour of type 1 gastric neuroendocrine tumours and suggest that a
      careful endoscopic follow-up, without any treatment, might represent a reasonable
      and safe option in selected patients.

PMID- 17433796
TI  - Impaired contractility of colonic muscle cells in a patient with chronic
      intestinal pseudo-obstruction.
AB  - Chronic intestinal pseudo-obstruction represents a cause of persistent functional
      intestinal failure either "secondary" to specific conditions or "chronic
      intestinal idiopathic pseudo-obstruction" in origin. The diagnosis is mainly
      clinical, supported by radiological and/or endoscopic findings excluding any
      mechanical cause of intestinal obstruction. We reported a case of a 39-year-old
      woman with chronic intestinal idiopathic pseudo-obstruction, who underwent
      colectomy with ileorectal anastomosis; histological examination of the surgical
      specimen did not reveal myogenic or neurogenic defects or other pathological
      abnormalities indicative of an underlying neuromuscular impairment. Because of
      the apparent integrity of the gut neuromuscular layer, we tested whether a
      functional impairment affected colonic single smooth muscle cells. Muscle cells
      were isolated from the right colon and their contractile response to a receptor
      dependent agonist evaluated in comparison to that obtained from controls. The
      cell contraction induced by acetylcholine in a dose response manner was markedly
      decreased in the patient affected by chronic intestinal idiopathic pseudo
      obstruction compared with cells from controls (percentage of cell shortening with
      maximal dose of acetylcholine [10(-6)M]: 10.7+/-3% versus 34.2+/-4%,
      respectively). The present findings indicate a specific defect of colonic smooth
      muscle cells likely related to an ineffective response to acetylcholine.

PMID- 17433797
TI  - Video-capsule endoscopy gastric and small bowel transit time and completeness of
      the examination in patients with diabetes mellitus.
AB  - BACKGROUND: Small intestine video-capsule endoscopy examination in patients with
      diabetes mellitus may be incomplete due to delayed gastric emptying. AIM: To
      measure video-capsule endoscopy gastric and small bowel transit time and to
      assess the completeness of the examination in diabetes mellitus patients.
      METHODS: In this retrospective, case-control study, we examined capsule endoscopy
      videos from 29 consecutive diabetes mellitus patients. Fifty-eight matched for
      sex, type of preparation, age and reason for referral non-diabetic controls were
      selected from our video-capsule endoscopy database. Two independent experienced
      investigators measured transit times and assessed examinations' completeness.
      RESULTS: Video-capsule endoscopy gastric transit time was significantly longer in
      diabetes mellitus (87, 1-478 min) compared to non-diabetic patients (24, 4-108
      min, p<0.001). The caecum was visualized in 20/29 (69%) diabetes mellitus and
      52/58 (89.6%) non-diabetic controls (p=0.02). In 16 diabetes mellitus patients
      that video-capsule endoscopy reached the caecum, small bowel transit time was
      significantly shorter (261.2+/-55.5 min) compared to their 32 non-diabetic
      matched controls (302+/-62.7 min, p=0.03). CONCLUSIONS: Patients with type 2
      diabetes mellitus have prolonged video-capsule endoscopy gastric transit time
      compared to non-diabetic patients. Prospective studies are required to complete
      our understanding of video-capsule endoscopy transit times in the setting of
      diabetes mellitus.

PMID- 17433798
TI  - An 18-year-old woman, with Crohn's disease presenting with right coxalgia.

PMID- 17433799
TI  - Probiotic intervention decreases serum gastrin-17 in Helicobacter pylori
      infection.
AB  - BACKGROUND: Previously we showed that a probiotic combination with L. rhamnosus
      GG was beneficial as an adjuvant therapy during H. pylori eradication. AIM: To
      evaluate whether probiotic combination with LGG adheres to the upper
      gastrointestinal mucosa and modifies H. pylori colonisation and H. pylori induced
      inflammation. METHODS: Thirteen patients referred for gastroduodenoscopy received
      a drink consisting of equal doses (2.5x10(9)CFU) of LGG, L. rhamnosus LC705,
      Propionibacterium freudenreichii JS and Bifidobacterium lactis Bb12 daily.
      Recovery of probiotics in biopsies (antrum, corpus, duodenum) and faecal samples
      was evaluated by strain-specific quantitative polymerase chain reaction. H.
      pylori colonization and gastric inflammation was investigated by urease activity
      ((13)C-urea breath test), histology and serum pepsinogen I, II and gastrin-17
      measurements. RESULTS: Twelve patients were fully investigated; of these three of
      the patients had LGG adhering to the biopsies at end of the intervention. Other
      probiotic strains were not detected, even though the recovery of all individual
      probiotic strains from the faeces was significantly increased (p<0.01). After the
      treatment, the level of (13)C-urea breath test (p=0.063) and gastrin-17 (p=0.046)
      decreased. CONCLUSIONS: The decreases in (13)C-urea breath test and gastrin-17
      indicate that the probiotic combination exerts a beneficial effect on gastric
      mucosa in H. pylori infected patients. LGG showed marginal ability to adhere to
      the upper gastrointestinal tract mucosa.

PMID- 17433800
TI  - Severe skeletal dysplasia caused by undiagnosed hypothyroidism.
AB  - Due to increased awareness of early clinical signs and introduction of neonatal
      screening for congenital hypothyroidism, long-term untreated hypothyroidism has
      become rare. Nevertheless, neonatal screening for congenital hypothyroidism is
      not performed in all countries, and not every affected patient might be picked up
      by neonatal screening alone. Here we describe a case of congenital hypothyroidism
      due to an ectopic thyroid that was not diagnosed for 13 years and resulted in
      severe skeletal changes beside mental disablement. The patient showed coarse
      facial features (hypertelorism, broad flat nasal bridge, broad face) and a severe
      truncal shortening due to kyphoscoliosis of the spine. X-rays detected highly
      retarded bone age, a widely opened anterior fontanelle, immature, flat bodies of
      the vertebra with ventral beaked deformities mainly in the lumbar region and no
      ossification centres in the head of the femurs. In this patient we found no
      evidence for a mutation of the PAX8 gene known to cause an ectopic and/or
      hypoplastic thyroid.

PMID- 17433801
TI  - Evaluation of densitometric bone-muscle relationships in Crohn's disease.
AB  - BACKGROUND: Patients with Crohn's disease (CD) are 1.4 to 2.5 times more likely
      than the normal population to sustain a fracture but the factors involved in the
      pathogenesis are not clearly understood. Bone mass is affected both by nutrition
      and by muscular activity. Trauma excepted, the largest voluntary loads on bones
      come from muscle contraction, not body weight. AIM: To assess the relationship
      between bone mass (bone mineral content) and muscle mass (lean mass) in CD
      patients. METHODS: Adult CD patients who had had a whole body, lumbar and hip
      densitometric evaluation were selected. Information regarding age, gender,
      weight, duration of CD, age at diagnosis, use of glucocorticoids and disease
      activity during the year before densitometric evaluation and laboratory
      parameters were collected. RESULTS: Data from 65 patients (28.8+/-10.6 years,
      F=44, M=21) were analyzed. Lumbar bone mineral content (BMC), BMC in both hips,
      total and regional BMC significantly correlated with body weight and total and
      regional lean mass (LM). In multiple regression analysis, only total LM was shown
      to be independently associated with lumbar BMC, BMC in both hips and total BMC.
      LM in upper and lower limbs was shown to be independently associated with BMC in
      upper and lower limbs, respectively. CONCLUSIONS: These results suggest that
      muscular mass and activity, rather than overall body weight, are important
      determinants of bone mass and, hence of bone strength in Crohn's disease. Thus,
      the management of bone loss in inflammatory bowel disease should address the
      effects of both nutrition and exercise on muscle mass.

PMID- 17433802
TI  - Prenatal programming of skeletal development in the offspring: effects of
      maternal treatment with beta-hydroxy-beta-methylbutyrate (HMB) on femur
      properties in pigs at slaughter age.
AB  - Alteration in fetal growth and development in response to prenatal environmental
      conditions such as nutrition has long-term or permanent effects during postnatal
      life. The aim of this study was to investigate effects of beta-hydroxy-beta
      methylbutyrate (HMB) treatment of sows during the last 2 weeks of pregnancy on
      programming of skeletal development in the offspring. The study was performed on
      141 pigs born by 12 sows of Polish Landrace breed. Two weeks before delivery,
      pregnant sows were divided into two groups. The first group consisted of control
      sows (N=6) that were treated with placebo. Sows that were orally treated with
      beta-hydroxy-beta-methylbutyrate (N=6) at the dosage of 0.05 g/kg of body weight
      per day belonged to the second group. Newborn piglets were weighed and subjected
      to blood collection for determination of serum levels of growth hormone (GH),
      insulin-like growth factor-1 (IGF-1), insulin, leptin, glucose and bone alkaline
      phosphatase (BAP) activity and lipid profile. At the age of 6 months, the piglets
      were slaughtered, their femur was isolated for analysis and assessment of lean
      meat content of carcasses was performed. The effects of maternal administration
      with HMB on skeletal properties in the offspring were evaluated in relation to
      bone mineral density and geometrical and mechanical properties. Maternal
      treatment with HMB increased serum levels of GH, IGF-1 and BAP activity in the
      newborns by 38.0%, 20.0% and 26.0%, respectively (P<0.01). HMB administration
      significantly increased volumetric bone mineral density of the trabecular and
      cortical bone of femur in the offspring at the age of 6 months (P<0.001). The
      weight of femur and geometrical parameters such as cross-sectional area, second
      moment of inertia, mean relative wall thickness and cortical index were
      significantly increased after HMB treatment (P<0.05). HMB induced higher values
      of maximum elastic strength and ultimate strength of femur (P<0.01). Furthermore,
      lean meat content of carcass was significantly increased in the females born by
      HMB-treated sows (P<0.05). The obtained results showed that maternal
      administration with HMB has positive long-term effects on bone tissue and
      improves volumetric bone mineral density, geometrical and mechanical properties
      of femur in the offspring. These effects were connected with increased level of
      GH and IGF-1 in the newborns indicating involvement of improved somatotrophic
      axis function in prenatal programming of skeletal development in pigs.

PMID- 17433803
TI  - A novel mutation of TGF beta1 in a Chinese family with Camurati-Engelmann
      disease.
AB  - Camurati-Engelmann disease (CED) [OMIM 131300] is a rare autosomal dominant
      disorder characterized by bone pain and osteosclerosis affecting the diaphysis of
      long bones. It has been previously reported that CED is caused by mutations of
      the transforming growth factor beta 1 (TGF beta1) gene on chromosome 19q13.1
      q13.3. Until now, seven mutations (LLL12-13ins, Y81H, R156C, R218C, R218H, H222D,
      C225R) in Australian, French, Belgian, Japanese, and European families have been
      reported and these data showed that there was no correlation between the nature
      of the mutations and the variability of the clinical manifestations. In this
      study, we found a Chinese family with CED and observed some intra-familial
      clinical variability and symptoms that became more severe with the age. A new TGF
      beta1 mutation (E169K) in exon 2 was identified in the Chinese family using
      polymerase chain reaction, direct sequencing analysis of PCR products and single
      strand conformation polymorphism analysis. This mutation has not been previously
      reported in other countries in the world.

PMID- 17433804
TI  - The societal burden of osteoporosis in Sweden.
AB  - In osteoporosis, the bone mass is decreased, thereby increasing the risk of
      fractures. Common osteoporotic fractures include those at the hip, the spine and
      the forearm. Fractures are a burden to society; in terms of costs, morbidity and
      mortality. The main objective of this study was to estimate the burden of
      osteoporosis in Sweden. The study used a prevalence-based bottom-up approach to
      estimate the total annual burden of osteoporosis in Sweden. The burden was
      assessed from a societal perspective including medical care costs, non-medical
      care costs, informal care and indirect costs. Moreover, the value of quality
      adjusted life-years (QALYs) lost because of fractures was included in the total
      burden estimations. The total annual fracture cost was estimated at MSEK 5639,
      which is about 3.2% of the total health care costs in Sweden. Community care was
      the most important cost category accounting for 66% of the total annual cost
      followed by medical care costs (31%), informal care (2%) and indirect costs (1%).
      By combining the annual value of QALYs lost (MSEK 10354) and the annual fracture
      costs, the total annual societal burden of osteoporosis in Sweden was estimated
      at MSEK 15183. Assuming no changes in the age-differentiated fracture risk, the
      annual burden of osteoporosis was projected to increase to MSEK 26301 in the year
      2050. The present study shows the societal burden of osteoporosis in Sweden to be
      higher than previously perceived. This burden is substantial and must be
      acknowledged as an important health problem. Osteoporosis-related fractures do
      not only lead to high medical care costs but also to high community care costs.

PMID- 17433805
TI  - The fracture and osteoporosis clinic: 1-year results and 3-month compliance.
AB  - INTRODUCTION: A Fracture and Osteoporosis (F&O) clinic started in two major
      general hospitals in the South of the Netherlands on April 1st 2004. Its
      objectives were to perform easy and complete assessment of female and male
      patients aged 50 years and over, initially treated for a low-energy trauma
      fracture, and to evaluate its effectiveness for early diagnosis and treatment of
      osteoporosis. METHODS: All eligible patients were selected from the digital X-ray
      system of the Emergency Department. DXA-scans and, if indicated, spinal
      radiographs were made. If osteoporosis was diagnosed, the F&O nurse explained the
      treatment strategy. Treatment advice was sent to the general practitioner (GP),
      who prescribed medication and provided further support. After 3 months, all
      osteoporosis patients received a compliance and side effects follow-up
      questionnaire. RESULTS: Up to June 1st 2005, 1058 patients followed the
      diagnostic procedure; 584 patients did not. Three times more women (804) than men
      (254) suffered a fracture. Osteoporosis occurred 10% more often in women.
      Overall, 37.1% had osteoporosis, based on DXA-scan only, and 39.6% when spinal
      radiographs were added. Spinal radiographs of the thoracic and or lumbar spine
      were made in 166 patients, radiographs of the thorax in 114 patients. Overall,
      fractures of the wrist were most common, with fractures of the hand occurring
      most frequently in men (20.0%). All fracture sites, except foot and clavicula,
      were associated with a higher frequency of osteoporosis than in the Dutch
      population. The response rate to the 3-month compliance questionnaire was 73%
      increasing to 96% after telephone contact. 86% visited their GP; 11% did not
      because they already received anti-osteoporotic medication prior to the fracture.
      Bisphosphonates were prescribed to 84% and discontinued by 7%. 13% reported side
      effects of bisphosphonates. Only half of the patients received the recommended
      calcium supplementation. CONCLUSIONS: The F&O clinic with its digital X-ray
      system facilitated easy, complete identification of fracture patients and early
      treatment of osteoporosis, which was frequently diagnosed. Self-reported
      compliance was high.

PMID- 17433806
TI  - Involvement of cellular prion protein in the nociceptive response in mice.
AB  - The role of the cellular prion protein (PrP(c)) in neuronal functioning includes
      neuronal excitability, cellular adhesion, neurite outgrowth and maintenance. Here
      we investigated the putative involvement of the PrP(c) function on the
      nociceptive response using PrP(c) null (Prnp(0/0)) and wild-type (Prnp(+/+)) mice
      submitted to thermal and chemical models of nociception. PrP(c) null mice were
      more resistant than wild-type mice to thermal nociception of the tail-flick test.
      However, no significant difference was found on the hot plate test. In the acetic
      acid-induced visceral nociception, PrP(c) null mice showed an enhanced response
      when compared to wild-type mice. However, there was no difference between
      Prnp(0/0) and wild-type mice on glutamate- and formalin-induced licking behaviour
      and Freund's Complete Adjuvant (FCA)-induced mechanical allodynia. PrP(c) null
      mice developed significantly lower paw edema than wild-type mice. In addition,
      the visceral conditioning stimuli produced by a previous injection of acetic acid
      (20 days before testing) significantly reduced early and late phases of formalin
      induced nociception in wild-type mice. In contrast, the same pre-treatment did
      not alter the formalin response in PrP(c) null mice. These results indicate a
      role of PrP(c) in the nociceptive transmission, including the thermal tail-flick
      test and visceral inflammatory nociception (acetic acid-induced abdominal
      constriction). Our findings show that PrP(c) is involved with a response mediated
      by inflammation (paw edema) and by visceral conditioning stimuli.

PMID- 17433807
TI  - Differential gene expression in the striatum of mice with very low expression of
      the vesicular monoamine transporter type 2 gene.
AB  - The vesicular monoamine transporter type 2 (VMAT2) packages pre-synaptic
      monoamines into vesicles. Previously, we generated mice hypomorphic for the VMAT2
      gene (Slc18a2), which results in a approximately 95% reduction in VMAT2 protein,
      disrupted vesicular storage, severe depletion of striatal dopamine and mice with
      moderate motor behaviour deficits. Dopamine released from mid-brain dopamine
      neurons acts on post-synaptic type 1 (D1) and 2 (D2) receptors located on
      striatal medium spiny neurons to initiate a signalling cascade that leads to
      altered transcription factor activity, gene expression and neuronal activity. We
      investigated striatal gene expression changes in VMAT2hypo mice by quantitative
      real-time PCR and in situ hybridisation. Despite unaltered expression of D1 and
      D2 dopamine receptors, there were dramatic alterations in striatal mRNAs encoding
      the neuropeptides substance P, dynorphin, enkephalin and cholecystokinin. The
      promoters of these genes are regulated by a combination of transcription factors
      that includes cAMP responsive element binding protein-1 (CREB) and c-Fos. Indeed,
      the changes in peptide mRNAs were associated with elevated expression of Creb1
      and c-Fos. These data indicate that striatal dopamine depletion, as a consequence
      of deficient vesicular storage in this mouse, triggers a complex program of gene
      expression, consistent with this mouse being an excellent model of Parkinson's
      disease.

PMID- 17433809
TI  - Reference intervals and decision limits for B-type natriuretic peptide (BNP) and
      its precursor (Nt-proBNP) in the elderly.
AB  - BACKGROUND: Elderly patients have the highest prevalence of heart failure (HF).
      The aims of the study were to establish a reference interval for B-type
      natriuretic peptide (BNP) and (Nt-proBNP) in elderly people, and to identify
      clinically relevant decision limits based on long-term outcome. METHODS: Plasma
      concentrations of BNP and Nt-proBNP were measured from two elderly populations:
      218 healthy subjects (mean age 73 years, population I), and 474 patients (mean
      age 73 years, population II) with symptoms associated with HF. Study population
      II was followed for 6 years with registration of all cardiovascular mortality.
      RESULTS: An association between both BNP and Nt-proBNP concentrations and age was
      found. The upper limit for the reference intervals in the healthy elderly
      (population I) was: BNP< or =28 pmol/L (< or =97 ng/L), and Nt-proBNP< or =64
      pmol/L (< or =540 ng/L). Based on cardiovascular mortality, decision limits for
      BNP (approximately 50 pmol/L, approximately 170 ng/L) and Nt-proBNP (
      approximately 200 pmol/L, approximately 1700 ng/L) (population II) were
      determined. CONCLUSIONS: Besides establishing reference intervals for BNP and Nt
      proBNP in an elderly population, a higher clinically relevant decision limit for
      BNP and Nt-proBNP was identified, indicating additive prognostic information of
      the peptides on top of measurements by echocardiography. Therefore, both
      reference intervals and decision limits should be included in clinical practice.

PMID- 17433808
TI  - Characterization of T9-T10 spinal neurons with duodenal input and modulation by
      gastric electrical stimulation in rats.
AB  - Gastric electrical stimulation (GES) has been suggested as a therapy for patients
      with gastric motility disorders or morbid obesity. However, it is unclear whether
      GES also affects intestinal sensory and motor functions. Furthermore, little is
      known about intraspinal visceroreceptive transmission and processing for duodenal
      afferent information. The aims of this study were to characterize responses of
      thoracic spinal neurons to duodenal distension, to determine the afferent pathway
      and to examine the effects of GES on activity of these neurons. Extracellular
      potentials of single T9-T10 spinal neurons were recorded in pentobarbital
      anesthetized, paralyzed, ventilated male rats (n=19). Graded duodenal distension
      (DD, 0.2-0.6 ml, 20 s) was produced by water inflation of a latex balloon
      surgically placed into the duodenum. One pair of platinum electrodes (1.0-1.5 cm
      apart) was sutured onto the serosal surface of the lesser curvature of the
      stomach. GES with four sets of parameters was applied for one minute: GES-A (6
      mA, 0.3 ms, 40 Hz, 2 s on, 3 s off), GES-B (6 mA, 0.3 ms, 14 Hz, 0.1 s on, 5 s
      off), GES-C (6 mA, 3 ms, 40 Hz, 2 s on, 3 s off) and GES-D (6 mA, 200 ms, 12
      pulses/min). Results showed that 33/117 (28%) spinal neurons responded to noxious
      DD (0.4 ml, 20 s). Of these, 7 (6%) neurons had low-threshold responses to DD
      (<or=0.2 ml) and 26 (22%) had high-threshold responses to DD (>or=0.4 ml). DD
      responsive spinal neurons were encountered more frequently in deeper (depth: 0.3
      1.2 mm) than in superficial laminae (depth: <0.3 mm) of the dorsal horn (24/67
      vs. 9/50, P<0.05). DD excited all 9 superficial neurons. In contrast, 20 deeper
      neurons were excited and 4 neurons were inhibited by DD. Activity of DD
      responsive neurons was affected more frequently with GES-C (13/15, 87%) than GES
      A (6/16, 38%), -B (3/15, 20%) and -D (5/14, 36%) (P<0.01). Bilateral cervical
      vagotomy did not significantly alter the effects of DD and GES on 5/5 neurons.
      Resiniferatoxin (2.0 microg/kg, i.v.), an ultrapotent agonist of transient
      receptor potential vanilloid receptor-1 (TRPV1), abolished DD responses and GES
      effects on all neurons examined in vagotomized rats. Additionally, 29/33 (88%) DD
      responsive neurons received inputs from somatic receptive fields on the back,
      flank and medial/lateral abdominal areas. It was concluded that GES mainly
      exerted an excitatory effect on T9-T10 spinal neurons with duodenal input
      transmitted by sympathetic afferent fibers expressing TRPV1; spinal neuronal
      responses to GES were strengthened with an increased pulse width and/or frequency
      of stimulation; T9-T10 spinal neurons processed input from the duodenum and might
      mediate effects of GES on duodenal sensation and motility.

PMID- 17433810
TI  - The significance of evaluating conventional inflammatory markers in Von
      Willebrand factor measurement.
AB  - BACKGROUND: The appropriate clinical interpretation of Von Willebrand factor
      (VWF) measurements is crucial since inherited or acquired deficiencies are
      responsible for a potentially life threatening bleeding disorder, whereas
      increased plasma concentrations may be associated with an increased thrombotic
      risk. Besides age and blood group, the variability introduced by the presence of
      an acute phase response might contribute to decrease the clinical usefulness of
      this measurement. METHODS: To investigate the relationship between conventional
      inflammatory markers and VWF, 387 consecutive unselected patients undergoing
      surgical procedures at our University Hospital were systematically investigated
      for routine laboratory testing, including also VWF Antigen (VWF:Ag), C-reactive
      protein (CRP) and the erythrocyte sedimentation rate (ESR) as parts of a routine
      preoperative screening program. RESULTS: After stratifying the study population
      according to the upper limit of the reference range of the two inflammatory
      markers, a significantly increased median VWF:Ag plasma concentration was
      observed for subjects with increased value of both CRP (CRP>5 mg/L=VWF:Ag>120
      UI/dL; CRP<5 mg/L=VWF:Ag 98 UI/dL, p=0.003) and ESR (ESR>30 mm/hg=VWF:Ag>120
      UI/dL; ESR<30 mm/hg=VWF:Ag 96 UI/dL, p<0.001). A significantly different
      frequency distribution of VWF:Ag concentrations was also observed in subjects
      with values of inflammatory markers above the upper limits of the reference
      ranges when compared to those with normal values. In particular, the prevalence
      of subjects with VWF:Ag levels>120 UI/dL was six- and nearly three-times higher
      in subjects with abnormal values of CRP (55.8% versus 9.3%, p<0.001) and ESR
      (54.5% versus 18.7%, p<0.001), respectively. CONCLUSIONS: Results of this
      investigation demonstrate that the evaluation of conventional inflammatory
      markers would represent a valuable tool to enhance the clinical usefulness of VWF
      measurements, especially in patients with transitory and subclinical
      inflammation. Since VWF and factor VIII are likely to increase in parallel, we
      suggest that their measurements should be repeated at least after 6 months to one
      year in the presence of concomitantly increased values of inflammatory markers,
      such as ESR and/or CRP.

PMID- 17433811
TI  - Paraoxonase, total antioxidant activity and peroxide levels in marasmic children:
      relationships with leptin.
AB  - OBJECTIVES: The aim of this study was to investigate the oxidant/antioxidant
      status, paraoxonase (PON) activity and leptin levels in children with marasmic
      malnutrition. DESIGN AND METHODS: Thirty marasmic children (age 14.4+/-10.3
      months) and 28 control subjects were included. Plasma PON activity, total
      antioxidant activity (TAO), total peroxide (TPX) and leptin levels were measured.
      RESULTS: Malnourished children had significantly lower leptin (3.6+/-1.1 vs.
      11.8+/-4.5 ng/mL, P<0.001), PON activity (66.4+/-28.6 vs. 221.3+/-31.6 IU/L,
      P<0.001) and TAO (1.44+/-0.12 vs. 2.45+/-0.61 mmol Trolox equiv/L, P<0.001); and
      higher TPX (15.6+/-6.4 vs. 5.9+/-1.9 micromol/L, P<0.001) values than in
      controls. Significant negative correlation was found between PON and TPX
      (P=0.040) and positive correlation between TAO and BMI (P=0.034) in patients. No
      significant correlation was found between leptin and oxidant/antioxidant
      parameters (P>0.05). CONCLUSIONS: Children with marasmic malnutrition had
      increased pro-oxidant and decreased antioxidant status. Extent of oxidative
      stress increases with malnutrition severity. Antioxidants could be given during
      nutritional rehabilitation.

PMID- 17433812
TI  - Clathrin-coated vesicles form a unique net-like structure in liver sinusoidal
      endothelial cells by assembling along undisrupted microtubules.
AB  - Liver sinusoidal endothelial cells (LSECs) are highly active professional
      scavenger cells using clathrin-mediated endocytosis to clear the blood from
      macromolecular waste products. Using confocal microscopy, we observed a
      remarkable net-like distribution of clathrin heavy chain (CHC) in LSECs while all
      other cell types examined including various primary endothelial cells and cell
      lines showed the well-known punctuate staining pattern representing clathrin
      coated vesicles (CCV). The net-like distribution of CHC in LSECs co-localized
      fully with microtubules, but not with actin. Upon 3D imaging, the net-like
      distribution of CHC resolved into numerous CCVs organized along the microtubules.
      The CCVs only partially co-localized with early endosome antigen 1 (EEA1) and
      adaptor protein 2 (AP-2). Endocytic vesicles containing ligand destined for
      degradation (FITC-AHGG) were organized along the clathrin/tubulin net-like
      structures, whereas transferrin-containing recycling vesicles co-localized to a
      much lower extent. Disruption of the microtubules by nocodazole treatment caused
      a collapse of the net-like organization of CCVs as well as a profound
      redistribution of EEA1, AP-2 and FITC-AHGG-containing vesicles, while transferrin
      internalization and recycling remained unaffected.

PMID- 17433813
TI  - Lack of association between polycystic ovary syndrome and embryonic aneuploidy.
AB  - OBJECTIVE: To determine whether women with polycystic ovary syndrome (PCOS) are
      at increased risk for embryonic aneuploidy. DESIGN: Retrospective cohort study.
      SETTING: Academic teaching department, privately owned preimplantation genetics
      laboratory, and academically affiliated, private infertility center. PATIENT(S):
      The study included 174 women, ages 27-45 years, who underwent a single cycle of
      controlled ovarian hyperstimulation with gonadotropins for in vitro
      fertilization. Amongst those, 74 were proven patients with PCOS, and 100 were
      control women with proven absence of PCOS. INTERVENTION(S): Preimplantation
      genetic diagnosis for chromosomes X, Y, 13, 15, 16, 17, 18, 21, and 22. MAIN
      OUTCOME MEASURE(S): Embryonic morphology, in vitro fertilization cycle outcome
      parameters, and euploidy and aneuploidy rates. RESULT(S): Women with PCOS
      demonstrated similar overall percentages of euploid embryos (49.1% +/- 28.1) when
      compared with control women (51.8% +/- 30.1). However, a statistically
      significantly higher oocyte yield in patients with PCOS (22.8 +/- 9.8 vs. 16.5 +/
      7.6) resulted in statistically significantly higher absolute numbers of euploid
      embryos (3.3 +/- 2.1 vs. 2.4 +/- 2.0). When stratified for age (<38 y and >or=38
      y) and egg numbers (10-20 and >20), euploidy rates still did not vary between
      study and control patients. High-responder patients with PCOS showed, however,
      statistically significantly reduced clinical- (42.9% vs. 69.0%) and ongoing
      pregnancy rates (40.5% vs. 65.5%) compared with high-responder control women.
      CONCLUSION(S): Women with PCOS are not at increased risk for embryonic aneuploidy
      in the course of in vitro fertilization treatment. Indeed, because of their
      larger oocyte numbers, they produce more euploid embryos but have lower pregnancy
      rates after high oocyte yields. This lower pregnancy rate is, thus, not
      genetically caused and requires further investigation.

PMID- 17433814
TI  - Obstetric outcome following laparoscopic adjustable gastric banding.
AB  - OBJECTIVE: To evaluate obstetric outcomes following laparoscopic adjustable
      gastric banding (LAGB) in obese women. METHODS: Obstetric outcomes were compared
      in a retrospective case-control study with 427 obese women, 13 who underwent LABG
      and 414 who did not. RESULTS: The mean weight gain during pregnancy was
      significantly lower in the LABG group than among controls (5.5 kg vs. 7.1 kg;
      P<0.05). The incidence of pre-eclampsia, gestational diabetes mellitus, low birth
      weight, and fetal macrosomia was less in the LABG group (P<0.05), and the
      incidence of cesarean deliveries during labor was half in the LAGB group (15.3%
      vs. 34.4%; P<0.01). Neonatal outcomes were not significantly different in the 2
      groups. CONCLUSIONS: Among obese women, the incidence of adverse obstetric
      outcomes was less in those who underwent LABG than in those who did not. These
      results suggest that obese women who wish to become pregnant would decrease their
      risk of obstetric complications if they first underwent LAGB.

PMID- 17433815
TI  - Design, calibration and pre-clinical testing of an instrumented tibial tray.
AB  - An instrumented tibial tray was developed that enables the measurement of six
      load components in a total knee arthroplasty (TKA). The design is fully
      compatible with a commonly available knee arthroplasty product since it uses the
      original tibial insert and femoral component. Two plates with hollow stems made
      from titanium alloy are separated by a small gap. Six semiconductor strain gages
      are used for measuring the load-dependent deformation of the inner hollow stem. A
      9-channel telemetry unit with a radio-frequency transmitter is encapsulated
      hermetically in the cavity of the prosthesis. The telemetry is powered
      inductively and strain gage signals are transmitted via a small antenna at the
      tip of the implant. The mean sampling rate is 125Hz. The calibration of the
      prosthesis resulted in an accuracy better than 2% mean measuring error. Fatigue
      testing of the implant was performed up to 10 million loading cycles and showed
      no failure. The pending in vivo application will give further insight into the
      kinetics of TKA. The measured values will enhance the quality of future pre
      clinical testing, numerical modeling in knee biomechanics and the patients'
      physiotherapy and rehabilitation.

PMID- 17433816
TI  - Numerical simulation of cardiovascular dynamics with different types of VAD
      assistance.
AB  - A variety of methods by which mechanical circulatory support (MCS) can be
      provided have been described. However, the haemodynamic benefits of the different
      methods have not been adequately quantified. The aim of this paper is to compare
      the haemodynamic effects of six forms of MCS by numerical simulation. Three types
      of ventricular assist device (VAD) are studied: positive displacement; impeller
      and a novel reciprocating-valve design. Similarly, three pumping modes are
      modelled: constant flow; counterpulsation and copulsation. The cardiovascular
      system is modelled using an approach developed previously, using the concentrated
      parameter method by considering flow resistance, vessel elasticity and inertial
      effects of blood in individual conduit segments. The dynamic modelling of
      displacement and impeller pumps is represented by VAD inlet/outlet flow-rate
      changes. The dynamics of the reciprocating-valve pump is modelled with a
      specified displacement profile. Results show that in each simulation, the
      physiological variables of mean arterial pressure and systemic flow are
      adequately maintained. Modulation of the impeller pump flow profile produces a
      small (5 mmHg) oscillatory component to arterial pressure, whereas the
      displacement and reciprocating-valve pumps generate substantial arterial pressure
      and flow pulsatility. The impeller pump requires the least power input, the
      reciprocating valve pump slightly more, and the displacement pump the most. The
      in parallel configuration of the impeller and displacement pump designs with
      respect to the left ventricle provides near complete unloading and can cause the
      aortic valve to remain closed throughout the entire cardiac cycle with the
      attendant risk of aortic valve leaflet fusion following prolonged support. The in
      series configuration of the reciprocating-valve pump avoids this shortcoming but
      activation must be carefully synchronized to the cardiac cycle to allow adequate
      coronary perfusion. The reciprocating-valve pump is associated with haemodynamic
      advantages and a favourable power consumption.

PMID- 17433817
TI  - Use of antigen mimics to produce specific antibodies to anti-coccidial drugs.
AB  - A range of polyclonal antibodies was successfully produced to the coccidiostatic
      drugs diclazuril and robenidine. Initial attempts to make immunogenic complexes
      of both drugs were ineffective due to difficulties encountered while trying to
      couple the compounds to large carrier proteins. Structural mimics, which could
      act as haptens for each drug, were sought and identified. The compounds
      identified were more open to chemical manipulation and were conjugated to carrier
      proteins to produce effective immunogens. The most sensitive antisera produced
      displayed IC50s of 1.5 ng/ml and 13 ng/ml for diclazuril and robenidine
      respectively. The antibody for diclazuril was shown to be specific, cross
      reacting only with clazuril by 15%. The robenidine antibody displayed a low cross
      reactivity of 1.2% to the compound used to produce the antibody.

PMID- 17433818
TI  - How can organellar protein N-terminal sequences be dual targeting signals? In
      silico analysis and mutagenesis approach.
AB  - Organellar nuclear-encoded proteins can be mitochondrial, chloroplastic or
      localized in both mitochondria and chloroplasts. Most of the determinants for
      organellar targeting are localized in the N-terminal part of the proteins, which
      were therefore analyzed in Arabidopsis thaliana. The mitochondrial, chloroplastic
      and dual N-terminal sequences have an overall similar composition. However, Arg
      is rare in the first 20 residues of chloroplastic and dual sequences, and Ala is
      more frequent at position 2 of these two types of sequence as compared to
      mitochondrial sequences. According to these observations, mutations were
      performed in three dual targeted proteins and analyzed by in vitro import into
      isolated mitochondria and chloroplasts. First, experiments performed with wild
      type proteins suggest that the binding of precursor proteins to mitochondria is
      highly efficient, whereas the import and processing steps are more efficient in
      chloroplasts. Moreover, different processing sites are recognized by the
      mitochondrial and chloroplastic processing peptidases. Second, the mutagenesis
      approach shows the positive role of Arg residues for enhancing mitochondrial
      import or processing, as expected by the in silico analysis. By contrast,
      mutations at position 2 have dramatic and unpredicted effects, either enhancing
      or completely abolishing import. This suggests that the nature of the second
      amino acid residue of the N-terminal sequence is essential for the import of dual
      targeted sequences.

PMID- 17433819
TI  - Novel families of toxin-like peptides in insects and mammals: a computational
      approach.
AB  - Most animal toxins are short proteins that appear in venom and vary in sequence,
      structure and function. A common characteristic of many such toxins is their
      apparent structural stability. Sporadic instances of endogenous toxin-like
      proteins that function in non-venom context have been reported. We have utilized
      machine learning methodology, based on sequence-derived features and guided by
      the notion of structural stability, in order to conduct a large-scale search for
      toxin and toxin-like proteins. Application of the method to insect and mammalian
      sequences revealed novel families of toxin-like proteins. One of these proteins
      shows significant similarity to ion channel inhibitors that are expressed in cone
      snail and assassin bug venom, and is surprisingly expressed in the bee brain. A
      toxicity assay in which the protein was injected to fish induced a strong yet
      reversible paralytic effect. We suggest that the protein may function as an
      endogenous modulator of voltage-gated Ca(2+) channels. Additionally, we have
      identified a novel mammalian cluster of toxin-like proteins that are expressed in
      the testis. We suggest that these proteins might be involved in regulation of
      nicotinic acetylcholine receptors that affect the acrosome reaction and sperm
      motility. Finally, we highlight a possible evolutionary link between venom toxins
      and antibacterial proteins. We expect our methodology to enhance the discovery of
      additional novel protein families.

PMID- 17433820
TI  - Therapeutic use of dextromethorphan: key learnings from treatment of pseudobulbar
      affect.
AB  - A variety of neurological conditions and disease states are accompanied by
      pseudobulbar affect (PBA), an emotional disorder characterized by uncontrollable
      outbursts of laughing and crying. The causes of PBA are unclear but may involve
      lesions in neural circuits regulating the motor output of emotional expression.
      Several agents used in treating other psychiatric disorders have been applied in
      the treatment of PBA with some success but data are limited and these agents are
      associated with unpleasant side effects due to nonspecific activity in diffuse
      neural networks. Dextromethorphan (DM), a widely used cough suppressant, acts at
      receptors in the brainstem and cerebellum, brain regions implicated in the
      regulation of emotional output. The combination of DM and quinidine (Q), an
      enzyme inhibitor that blocks DM metabolism, has recently been tested in phase III
      clinical trials in patients with multiple sclerosis and amyotrophic lateral
      sclerosis and was both safe and effective in palliating PBA symptoms. In
      addition, clinical studies pertaining to the safety and efficacy of DM/Q in a
      variety of neurological disease states are ongoing.

PMID- 17433822
TI  - Dairy goat production and the importance of gastrointestinal strongyle
      parasitism.
AB  - In recent years, demand for goat products has increased in both developing and
      developed countries. Goat production (particularly dairy), however, is negatively
      affected by several factors, including infectious and parasitic diseases. Among
      the latter, gastrointestinal strongyle infection remains one of the main
      constraints to dairy goat production. In this mini-review, we emphasize the
      negative influence of these parasites, associated with subclinical production
      losses and depressive impacts upon long-term animal productivity, as well as the
      scarcity of studies on this topic. Finally, the necessity of reducing the use of
      anthelminthics and thus minimizing residues in food and the environment is
      stressed.

PMID- 17433823
TI  - Effect of estrogen and inhibition of phosphatidylinositol-3 kinase on Akt and
      FOXO1 in rat uterus.
AB  - The importance of FOXO transcription factors in regulating different aspects of
      cellular homeostasis and apoptosis has become apparent. Akt/protein kinase B has
      been shown to phosphorylate and inactivate members of FOXO family of
      transcription factors. Akt and its upstream regulator, phosphatidylinositol-3
      kinase (PI3K) are involved in rapid action of estrogen (E2) in different cells
      and tissues. The aim of the present study was to analyze the E2/PI3K/Akt/FOXO
      pathway in rat uterus. In response to E2, phosphorylation of Akt/PKB on Ser473
      and FOXO1 on Ser256 and Thr24 residues increased but with distinct kinetics,
      regulating the activation and inactivation of Akt and FOXO1 proteins,
      respectively. The antiestrogen ICI 182,780 prevented E2 induced Akt activation
      suggesting that estrogen receptors mediate this effect of E2. Intrauterine
      injection of Wortmannin caused a decrease in the phosphorylation of Ser473 of
      Akt, and attenuated phosphorylation of its downstream target FOXO1 at Ser256 and
      at Thr24. However, the effect of E2 on phosphorylation of Thr24 showed a kinetic
      pattern distinct from that of Ser256. Our results suggest that the
      E2/PI3K/Akt/FOXO1 pathway in rat uterus is functioning even at the lack of
      ovarian hormones and responses to E2 treatment. Estradiol increases Akt
      phosphorylation through a Wortmannin sensitive way, presumably involving PI3K.
      The present work shows that PI3K plays a crucial role in the phosphorylation and
      inactivation of FOXO1 in vivo, indicating that the regulation of this
      transcription factor is a more complex event in uterine cells requiring further
      investigations.

PMID- 17433821
TI  - Steroid modulation of GABAA receptor-mediated transmission in the hypothalamus:
      effects on reproductive function.
AB  - The hypothalamus, the seat of neuroendocrine control, is exquisitely sensitive to
      gonadal steroids. For decades it has been known that androgens, estrogens and
      progestins, acting through nuclear hormone receptors, elicit both organizational
      and activational effects in the hypothalamus and basal forebrain that are
      essential for reproductive function. While changes in gene expression mediated by
      these classical hormone pathways are paramount in governing both sexual
      differentiation and the neural control of reproduction, it is also clear that
      steroids impart critical control of neuroendocrine functions through non-genomic
      mechanisms. Specifically, endogenous neurosteroid derivatives of
      deoxycorticosterone, progesterone and testosterone, as well and synthetic
      anabolic androgenic steroids that are self-administered as drugs of abuse, elicit
      acute effects via allosteric modulation of gamma-aminobutyric acid type A
      receptors. GABAergic transmission within the hypothalamus and basal forebrain is
      a key regulator of pubertal onset, the expression of sexual behaviors, pregnancy
      and parturition. Summarized here are the known actions of steroid modulators on
      GABAergic transmission within the hypothalamus/basal forebrain, with a focus on
      the medial preoptic area and the supraoptic/paraventricular nuclei that are known
      to be central players in the control of reproduction.

PMID- 17433824
TI  - Synthesis of some steroidal oximes, lactams, thiolactams and their antitumor
      activities.
AB  - The antiproliferative activity of previously synthesized (Z)-cholest-4-en-6-one
      oxime (1), (E)-cholest-4-en-6-one oxime (2), 7-aza-B-homocholest-4-en-6-one (3)
      and 6-aza-B-homocholest-4-en-7-one (4) and newly synthesized 6-thioxo-7-aza-B
      homocholest-4-ene (5) and 6-aza-7-thioxo-B-homocholest-4-ene (6) was tested for
      their possible effects against two human tumor cell lines, cervical carcinoma
      (HeLa) and chronic myelogenous leukemia (K-562). Compounds 1-6, exerted a dose
      dependent antiproliferative effect toward cell lines used in experimental design,
      showing high selectivity in their action for tumor cells in comparison to normal
      immunocompetent cells (non-stimulated PBMC and PHA-stimulated PBMC). Compounds 2,
      3 and 4 exhibited a very high but selective antitumor activity, by inducing
      apoptosis in sensitive, for that purpose targeted tumor cell line (HeLa cells).
      Low toxic effect upon both non-stimulated, and PHA stimulated PBMCs from control,
      healthy volunteers, has been detected for compounds 1, 2, 3 and 4. The possible
      reasons for profound differences in the effects of this spectrum of steroidal
      compounds between tumor cell lines and normal stimulated and non-stimulated PBMCs
      are discussed. The molecular mechanisms for apoptotic events in HeLa cell line
      are suggested. The guidelines for further research are underlined.

PMID- 17433825
TI  - New age constraints on the Middle Stone Age occupations of Kharga Oasis, Western
      Desert, Egypt.
AB  - Spring-deposited carbonate rocks, or tufas, exposed along the flanks of the
      Libyan Plateau near Kharga Oasis, Western Desert, Egypt, can provide a directly
      datable stratigraphic context for Middle Stone Age/Middle Paleolithic (MSA/MP)
      archaeological material, if such material can be found in situ within tufa
      strata. Two such localities (Mata'na Site G and Bulaq Wadi 3 Locus 1) described
      by Caton-Thompson were revisited and sampled for uranium-series analysis. At
      Mata'na Site G (KH/MT-02), Middle Stone Age ("Upper Levalloisian") material is
      underlain by tufa with a uranium-series age of 127.9+/-1.3 ka, and overlain by
      tufa with an age of 103+/-14 ka. At Bulaq Wadi 3 Locus 1, a uranium-series age of
      114.4+/-4.2 ka on tufa capping a small collection of Middle Stone Age artifacts
      also provides a minimum age constraint on that material. Tufa underlying an MSA
      workshop (KH/MD-10) indicates that this assemblage, characterized by use of
      several Levallois reduction methods, was deposited after approximately 124 ka.
      Furthermore, uranium-series ages averaging approximately 133 ka on a Wadi
      Midauwara tufa (WME-10) without associated archaeological material suggest that
      one period of spring flow in the region began during the Marine Isotope Stage
      6/5e transition, prior to the warmest portion of the last interglacial period.
      The dated archaeological material suggests that the distinction that has been
      identified between Nubian and non-Nubian complexes in the Nile Valley may hold
      for the Western Desert, although local complexity has yet to be fully described.

PMID- 17433826
TI  - Circulating CD40 ligand in peripheral arterial disease.

PMID- 17433827
TI  - The relationship between c-FLIP expression and human papillomavirus E2 gene
      disruption in cervical carcinogenesis.
AB  - OBJECTIVE: Human papillomavirus (HPV) is the essential causative factor in
      cervical carcinogenesis, and apoptosis inhibition is one of the key features of
      HPV-induced malignant transformation. This study is to investigate the possible
      cause-effect association between high-risk HPV and cellular FLICE-like inhibitory
      protein (c-FLIP), an important apoptosis regulator, during cervical
      carcinogenesis. METHODS: A series of 80 archival samples, including 20 squamous
      cervical carcinomas (SCC) 54 cervical intraepithelial neoplasia (CIN) lesions and
      6 normal cervical tissues, were subjected for c-FLIP immunohistochemical staining
      and HPV HC-II analysis. Typing HPV-16 infection was analyzed by the polymerase
      chain reaction (PCR), and its status was assessed with the integrity and
      disruption of the HPV-16 E2 gene, which was amplified in three overlapping
      fragments. RESULTS: The types of HR-HPV infection and E2 disruption were
      associated closely with cervical lesion severity. There was a significant
      relationship between lesion grade and c-FLIP expression level. c-FLIP
      overexpression was also closely associated with HR-HPV infection and its
      integration status. Multivariate regression analysis revealed c-FLIP as a strong
      independent predictor for CIN, with 100% PPV, and showed 90.9% PPV in detecting
      HR-HPV, and remained a significance factor to rule out which case has no HR-HPV
      integration, with a 94.7% sensitivity and a 90.0% NPV. CONCLUSIONS: The present
      data approved that c-FLIP overexpression is related significantly to the presence
      of HR-HPV infection and its integration status during progression of cervical
      squamous cell cancer and confirmed the role of c-FLIP as an early marker of
      cervical carcinogenesis.

PMID- 17433828
TI  - Association between CD4(+)CD25(high) T cells and atopy in children.
AB  - BACKGROUND: There is evidence that CD4(+)CD25(high) T-regulatory cells are
      important for establishing tolerance to allergens, but information in children is
      limited. OBJECTIVE: To test the hypothesis that greater numbers and function of
      CD4(+)CD25(high) T cells are associated with a reduced risk of childhood
      allergies and wheezing. METHODS: A cohort of 151 six-year-old children from
      atopic families was analyzed for peripheral blood CD4(+)CD25(high) and
      CD4(+)CD25(int) T cells by flow cytometry and for clinical and immunologic
      correlates of atopy. The associations between these variables were assessed by
      regression analysis. RESULTS: Factors positively associated with %
      CD4(+)CD25(high)/CD4 T cells were male sex, number of positive allergen-specific
      IgE tests, total IgE, season, and 1-month average total pollen count preceding
      blood draw. The percentage of CD4(+)CD25(high)/total CD4 T cells did not
      correlate with induced cytokine production, and correlated negatively with
      suppressive capacity of CD4(+)CD25(+) T cells (r = -0.45; P = .034). The
      percentage of CD4(+)CD25(int)/CD4 T cells was 54% higher in pollen-sensitized
      children compared with nonsensitized children in spring (P = .023 for
      interaction), and correlated positively with IL-5, IL-10, and IL-13 (P < or =
      .001 for all). CONCLUSION: Our findings suggest that blood CD4(+)CD25(high) cells
      are a mixture of activated and regulatory T cells, and that these cells could be
      seasonally regulated by environmental factors such as pollen exposure. CLINICAL
      IMPLICATIONS: Seasonal increases in CD4CD25(high) expression in children with
      allergy may represent systemic immune activation caused by pollen exposures.

PMID- 17433829
TI  - American Academy of Allergy, Asthma & Immunology Work Group report: exercise
      induced asthma.

PMID- 17433830
TI  - A novel mutation of intron 22 in Janus kinase 3-deficient severe combined
      immunodeficiency.

PMID- 17433831
TI  - Improved asthma outcomes with a simple inhaler technique intervention by
      community pharmacists.

PMID- 17433832
TI  - Mitogen-activated protein kinase proteins regulate LPS-stimulated release of pro
      inflammatory cytokines and prostaglandins from human gestational tissues.
AB  - The role of pro-inflammatory cytokines and prostaglandins in human labour is well
      established. Many of the mRNAs stabilised by the MAPK pathway encode inflammatory
      mediators, suggesting that this kinase pathway plays a major role in the
      regulation of inflammation. The aim of this study was to determine if the MAPK
      pathway regulates the inflammatory response in human gestational tissues.
      Placenta and fetal membranes (n=5) obtained from pregnant women undergoing
      Caesarean section before the onset of labour were exposed to LPS, and co
      incubated in the absence or presence of 12.5, 25 and 50 microM U0126 (ERK 1/2
      inhibitor), SB202190 (p38 MAPK inhibitor) and SP600125 (JNK inhibitor). After 18
      h incubation, tissues were collected and ERK 1/2, p38 MAPK, and JNK total and
      phosphorylated protein expression was assessed by ELISA and/or Western blotting.
      The incubation medium was collected and TNF-alpha, IL-1beta, IL-6, IL-8, PGE(2)
      and PGF(2alpha) release was quantified by ELISA. Treatment of placenta and fetal
      membranes with LPS activated all three MAPK proteins. Co-incubation with U0126,
      SP600125 and SB202190 significantly suppressed LPS-stimulated activation of ERK
      1/2, JNK, and p38 MAPK, respectively. All cytokine and prostaglandin release was
      significantly suppressed by all concentrations of U0126. LPS-stimulated IL-6, TNF
      alpha, PGE(2) and PGF(2alpha) release was significantly suppressed by treatment
      with all concentrations of SB202190, whereas ILS-stimulated IL-1beta release was
      only significantly inhibited in the presence of 50 microM SB202190 and there was
      no effect of SB202190 on LPS-stimulated IL-8 release. SP600125 significantly
      repressed LPS-stimulated release of IL-1beta and TNF-alpha at all concentrations,
      whereas LPS-stimulated IL-6, PGE(2) and PGF(2alpha) release were inhibited at 25
      and 50 microM. In conclusion, the MAPK inhibitors used in this study demonstrated
      differential activity against a range of sequelae commonly associated with
      inflammation, supporting the therapeutic potential of MAPK inhibitors in
      pregnancy complications associated with an aberrant inflammatory response.

PMID- 17433833
TI  - Cell-derived microparticles and complement activation in preeclampsia versus
      normal pregnancy.
AB  - BACKGROUND: Inflammation plays a major role in the vascular dysfunction seen in
      preeclampsia, and several studies suggest involvement of the complement system.
      OBJECTIVES: To investigate whether complement activation on the surface of
      microparticles is increased in plasma of preeclamptic patients versus healthy
      pregnant controls. METHODS: Microparticles from plasma of preeclamptic (n=10),
      healthy pregnant (n=10) and healthy nonpregnant (n=10) women were analyzed by
      flow cytometry for bound complement components (C1q, C4, C3) and complement
      activator molecules (C-reactive protein [CRP], serum amyloid P component [SAP],
      immunoglobulin [Ig]M, IgG). Fluid phase complement activation products and
      activator molecules were also determined. RESULTS: Levels of microparticles with
      bound complement components showed no increase in complement activation on the
      microparticle surface in preeclamptic women, in line with levels of fluid phase
      complement activation products. In healthy nonpregnant and pregnant women, bound
      CRP was associated with classical pathway activation on the microparticle
      surface, and in healthy pregnant women IgM and IgG molecules also contributed. In
      preeclamptic women, microparticles with bound SAP and those with IgG seemed to
      contribute to C1q binding without a clear association to further classical
      pathway activation. Furthermore, significantly increased levels of microparticles
      with bound CRP were present in preeclamptic compared with healthy pregnant women
      (median 178x10(6)/L versus 47x10(6)/L, P<0.01), but without concomitant increases
      in complement activation. CONCLUSIONS: We found no evidence of increased
      complement activation on the microparticle surface in preeclamptic women.
      Microparticles with bound CRP were significantly increased, but in contrast to
      healthy pregnant and nonpregnant women, this was not associated with increased
      classical pathway activation on the surface of the microparticles.

PMID- 17433834
TI  - Diclofenac residues in carcasses of domestic ungulates available to vultures in
      India.
AB  - Gyps vulture populations across the Indian subcontinent are declining rapidly and
      evidence indicates that veterinary use of the non-steroidal anti-inflammatory
      drug (NSAID) diclofenac is the major cause. Exposure of vultures to diclofenac is
      likely to arise from the consumption of livestock carcasses that have been
      treated shortly before death, however, detailed information regarding the
      prevalence and residual levels of diclofenac in carcasses available to vultures
      in India remains unreported. Here, we present data on diclofenac residues in 1848
      liver samples taken from carcasses of dead livestock sampled at 67 sites in 12
      states within India, between May 2004 and July 2005. Diclofenac residues were
      detected in carcasses in all states except Orisa, where only one site was
      sampled. The overall prevalence of detectable diclofenac (>10 microg kg(-1))
      across all states was 10.1% and varied significantly among states, with up to
      22.3% prevalence determined in Bihar. The geometric mean concentration of
      diclofenac found in samples in which the drug was detected was 352 microg kg(-1).
      The prevalence of carcasses containing diclofenac is similar to that previously
      proposed to be required to have caused the observed Gyps vulture declines in
      India. On the 11th of May 2006, the Drug Controller General (India) ordered the
      withdrawal of all licenses granted for the manufacture of diclofenac for
      veterinary use within India. However, if Gyps vultures are to be protected,
      potentially substantial existing stocks now need to be quickly and effectively
      removed from the Indian veterinary market.

PMID- 17433835
TI  - New triple procedure: Descemet's stripping and automated endothelial keratoplasty
      combined with phacoemulsification and intraocular lens implantation.
AB  - PURPOSE: To evaluate visual acuity (VA), graft clarity, and refractive outcome of
      Descemet's stripping and automated endothelial keratoplasty (DSAEK) combined with
      phacoemulsification and intraocular lens (IOL) implantation in patients with
      coexisting Fuchs' endothelial dystrophy and immature senile cataracts. DESIGN:
      Pilot, prospective, noncomparative, surgical case series. PARTICIPANTS: Twenty
      one eyes of 21 consecutive patients with coexisting visually significant immature
      senile cataracts and Fuchs' corneal dystrophy with guttata of Descemet's membrane
      and either microcystic epithelial edema or stromal edema presenting to a single
      academic eye institute. METHODS: All patients underwent phacoemulsification and
      posterior chamber IOL implantation through temporal clear corneal incision,
      followed by DSAEK. The intent was to render all eyes as close to emmetropia as
      possible. MAIN OUTCOME MEASURES: Six-month postoperative best spectacle-corrected
      VA (BSCVA), refractive spherical equivalent (SE), refractive astigmatism, and
      keratometry. RESULTS: Average BSCVAs were 20/68 preoperatively and 20/34
      postoperatively (P<0.0001). The postoperative SE refractive error was +0.45
      diopters (D), on average +1.13 D more hyperopic than predicted by preoperative
      lens power calculations. Overall, 13 patients (62%) were within 1.00 D and 21
      (100%) were within 2.00 D of emmetropia postoperatively. Preoperative and
      postoperative average refractive astigmatisms were 1.46 D and 1.56 D,
      respectively (P = 0.69). Complications included graft dislocations requiring
      repositioning (3), 2 of which experienced recurrent dislocation requiring
      reoperation with a new graft; acute graft rejection (3); and pupillary block
      glaucoma (2). CONCLUSIONS: This pilot case series of 6-month results of DSAEK
      combined with phacoemulsification and IOL implantation suggests that it provides
      rapid visual rehabilitation with predictable refractive outcomes.

PMID- 17433836
TI  - From the Golgi-Cajal mapping to the transmitter-based characterization of the
      neuronal networks leading to two modes of brain communication: wiring and volume
      transmission.
AB  - After Golgi-Cajal mapped neural circuits, the discovery and mapping of the
      central monoamine neurons opened up for a new understanding of interneuronal
      communication by indicating that another form of communication exists. For
      instance, it was found that dopamine may be released as a prolactin inhibitory
      factor from the median eminence, indicating an alternative mode of dopamine
      communication in the brain. Subsequently, the analysis of the locus coeruleus
      noradrenaline neurons demonstrated a novel type of lower brainstem neuron that
      monosynaptically and globally innervated the entire CNS. Furthermore, the
      ascending raphe serotonin neuron systems were found to globally innervate the
      forebrain with few synapses, and where deficits in serotonergic function appeared
      to play a major role in depression. We propose that serotonin reuptake inhibitors
      may produce antidepressant effects through increasing serotonergic neurotrophism
      in serotonin nerve cells and their targets by transactivation of receptor
      tyrosine kinases (RTK), involving direct or indirect receptor/RTK interactions.
      Early chemical neuroanatomical work on the monoamine neurons, involving primitive
      nervous systems and analysis of peptide neurons, indicated the existence of
      alternative modes of communication apart from synaptic transmission. In 1986,
      Agnati and Fuxe introduced the theory of two main types of intercellular
      communication in the brain: wiring and volume transmission (WT and VT).
      Synchronization of phasic activity in the monoamine cell clusters through
      electrotonic coupling and synaptic transmission (WT) enables optimal VT of
      monoamines in the target regions. Experimental work suggests an integration of WT
      and VT signals via receptor-receptor interactions, and a new theory of receptor
      connexin interactions in electrical and mixed synapses is introduced.
      Consequently, a new model of brain function must be built, in which communication
      includes both WT and VT and receptor-receptor interactions in the integration of
      signals. This will lead to the unified execution of information handling and
      trophism for optimal brain function and survival.

PMID- 17433838
TI  - An operant serial implicit learning task (SILT) in rats: task acquisition,
      performance and the effects of striatal lesions.
AB  - We describe the serial implicit learning task (SILT), a novel test for assessing
      implicit and procedural learning in rodents, and have used the task to test
      whether striatal lesions disrupt the speed and accuracy of responding to stimulus
      response (S-R) sequences that may be either predictable or unpredictable. In this
      task, the rats must learn to respond to two consecutive stimulus lights, S1 and
      S2, which may occur on each trial in any of five alternative response locations,
      for food reward. For two of the S1 locations, the location of the subsequent S2
      is predictable, whereas for the other three S1 locations, the location of S2 is
      unpredictable and can appear with equal probability in any of the other four
      locations (i.e. any open hole other than S1 itself). All rats learned to make the
      serial responses rapidly and accurately. Effective implicit learning was
      demonstrated by there being a significant advantage in both speed and accuracy in
      responding to predictable than to unpredictable S2 stimuli. Following quinolinic
      acid lesions of the medial or lateral striatum, the lesioned rats showed
      significantly reduced accuracy and increased latencies in responding to both S1
      and S2, although (contrary to initial hypothesis) the benefits of predictability
      of S2 were retained. These data establish a novel and efficient operant test for
      implicit learning in the rat.

PMID- 17433837
TI  - Pulvinar contributions to the dorsal and ventral streams of visual processing in
      primates.
AB  - The visual pulvinar is part of the dorsal thalamus, and in primates it is
      especially well developed. Recently, our understanding of how the visual pulvinar
      is subdivided into nuclei has greatly improved as a number of histological
      procedures have revealed marked architectonic differences within the pulvinar
      complex. At the same time, there have been unparalleled advances in understanding
      of how visual cortex of primates is subdivided into areas and how these areas
      interconnect. In addition, considerable evidence supports the view that the
      hierarchy of interconnected visual areas is divided into two major processing
      streams, a ventral stream for object vision and a dorsal stream for visually
      guided actions. In this review, we present evidence that a subset of medial
      nuclei in the inferior pulvinar function predominantly as a subcortical component
      of the dorsal stream while the most lateral nucleus of the inferior pulvinar and
      the adjoining ventrolateral nucleus of the lateral pulvinar are more devoted to
      the ventral stream of cortical processing. These nuclei provide cortico-pulvinar
      cortical interactions that spread information across areas within streams, as
      well as information relayed from the superior colliculus via inferior pulvinar
      nuclei to largely dorsal stream areas.

PMID- 17433839
TI  - Right ventricular restrictive physiology in repaired tetralogy of Fallot is
      associated with smaller respiratory variability.
AB  - BACKGROUND: Long-term outcomes of patients with repaired tetralogy of Fallot
      (TOF) are known to be related with right ventricular (RV) volume overload,
      severity of pulmonary insufficiency (PI) and the type of outflow repair. Right
      ventricular restrictive physiology (RVRP) has also been reported to interfere
      with several factors influencing the late result in repaired TOF patients.
      However, the mechanism and physiology of this unique myocardial property in the
      chronically overloaded right ventricle are not yet clearly understood. METHODS:
      We investigated 43 patients after repair of TOF to assess the relationships among
      biventricular diastolic function, volume characteristics, and influence of
      respiratory effort. The patients were classified into 3 groups; 15 patients with
      RVRP and significant PI (RP group, 35%), 19 without RVRP in the presence of
      significant PI (NR+PI group, 44%), and 9 without RP or significant PI (NR-PI
      group, 21%). Doppler spectrals obtained by echocardiography from systemic and
      pulmonary veins, main pulmonary artery (MPA), and both ventricular inlets, and
      biventricular diastolic function were compared according to the respiratory
      cycle. RESULTS: The RP group revealed higher pulmonary venous systolic/diastolic
      flow ratio (S/D ratio) and the NR+PI group showed larger velocity-time integral
      (VTI) ratio of total regurgitant/antegrade flow at the MPA and more respiratory
      variability in the systemic vein. CONCLUSION: RP is associated with less volume
      overload of the RV and smaller respiratory variability is also associated with
      the restrictive RV. The diastolic function and volume status of the RV may
      influence the diastolic properties of the left heart.

PMID- 17433840
TI  - Comparison of angiotensin-converting enzyme inhibitor alone and in combination
      with irbesartan for the treatment of heart failure.
AB  - OBJECTIVE: Angiotensin-converting enzyme inhibitor (ACEI) is beneficial in
      patients with congestive heart failure (CHF). Some, but not all, angiotensin
      receptor blocker (ARB) was demonstrated to be effective as "add-on" therapy. We
      investigated whether irbesartan is useful as an add-on therapy in CHF. DESIGN:
      Randomized control trial. SETTING: Single center. PATIENTS: 50 CHF patients on
      stable doses of ACEI. INTERVENTIONS: Add-on therapy with irbesartan (300 mg/day)
      or continuation of conventional therapy (control group) for 1 year. MAIN OUTCOME
      MEASURES: Serial clinical and echocardiographic assessment were performed as
      baseline, 3 months and 1 year after therapy. RESULTS: There was no difference in
      clinical characteristics between 2 groups. Patients in the add-on therapy group
      had significant increase in 6-Minute Hall-Walk distance (351+/-89 to 392+/-84 m,
      P<0.01), achieved higher METs exercise time on treadmill test (3.9+/-1.1 to 4.6+/
      1.3 METs, P=0.01), reduction of NYHA Class (2.4+/-0.5 to 2.0+/-0.8, P<0.005) and
      improvement of QOL score (28+/-19 to 17+/-18, P<0.05). These parameters were not
      improved in the control group and a worsening of exercise capacity was observed
      (P<0.05). A reduction of left ventricular end-systolic diameter (4.94+/-0.85 vs
      4.30+/-1.17 cm, P<0.05) was observed in the add-on group. At the end of 1 year,
      more patients have normal or abnormal relaxation pattern in the add-on group than
      the control group (82% vs 53% chi(2)=7.1, P=0.02). Blood pressure and renal
      function were unchanged in both groups. CONCLUSION: The addition of irbesartan to
      conventional ACEI therapy in CHF further improves symptoms, exercise capacity and
      quality of life without adverse effects on hemodynamics and renal function.

PMID- 17433841
TI  - Gamma-delta T-cell-mediated dilated cardiomyopathy.
AB  - Gamma-delta T-cells are usually minor component of peripheral blood and lymphoid
      tissues, but may play an important role in autoimmune diseases. We here describe
      the first case of dilated cardiomyopathy (DCM) with heart infiltration by mostly
      gamma-delta T-cells, who improved significantly by steroid therapy. In general,
      steroid therapy has only a little effect on DCM, however these findings might
      have implications with respect to the selection of patients who might respond to
      immunosuppressive therapy.

PMID- 17433842
TI  - Is coronary revascularization necessary for patients with well-developed coronary
      collaterals and coronary artery disease?

PMID- 17433844
TI  - Membrane engineering in biotechnology: quo vamus?
AB  - Membranes are essential to a range of applications, including the production of
      potable water, energy generation, tissue repair, pharmaceutical production, food
      packaging, and the separations needed for the manufacture of chemicals,
      electronics and a range of other products. Therefore, they are considered to be
      "dominant technologies" by governments and industry in several prominent
      countries--for example, USA, Japan and China. When combined with catalysts,
      membranes are at the basis of life, and membrane-based biomimetism is a key tool
      to obtain better quality products and environmentally friendly developments for
      our societies. Biology has a main part in this global landscape because it
      simultaneously provides the "model" (with natural biological membranes) and
      represents a considerable field of applications for new artificial membranes
      (biotreatments, bioconversions and artificial organs). In this article, our
      objective is to open up this enthralling area and to give our views about the
      future of membranes in biotechnology.

PMID- 17433843
TI  - Protein aggregation in silico.
AB  - Protein aggregation is a challenge to the successful manufacture of protein
      therapeutics; it can impose severe limitations on purification yields and
      compromise formulation stability. Advances in computer power, and the wealth of
      computational studies pertaining to protein folding, have facilitated the
      development of molecular simulation as a tool to investigate protein misfolding
      and aggregation. Here, we highlight the successes of protein aggregation studies
      carried out in silico, with a particular emphasis on studies related to
      biotechnology. To conclude, we discuss future prospects for the field, and
      identify several biotechnology-related problems that would benefit from molecular
      simulation.

PMID- 17433845
TI  - Reduced terpene levels in cottonseed add food to fiber.
AB  - Using RNA interference (RNAi) technology, the levels of a toxic phytoprotectant
      have recently been reduced specifically in the seeds of cotton to generate a
      novel dual-purpose crop. By engineering an endogenous terpene pathway, there is
      now the exciting potential for an added-value, genetically modified crop with the
      cash value of the fiber supported by the improved nutritional value and expanded
      food and feed use for the cottonseed, which is normally a low-value by-product.

PMID- 17433846
TI  - Brave new (strept)avidins in biotechnology.
AB  - Avidin and streptavidin are widely used in (strept)avidin-biotin technology,
      which is based on their tight biotin-binding capability. These techniques are
      exceptionally diverse, ranging from simple purification and labeling methods to
      sophisticated drug pre-targeting and nanostructure-building approaches.
      Improvements in protein engineering have provided new possibilities to develop
      tailored protein tools. The (strept)avidin scaffold has been engineered to extend
      the existing range of applications and to develop new ones. Modifications to
      (strept)avidins--such as simple amino acid substitutions to reduce biotin binding
      and alter physico-chemical characters--have recently developed into more
      sophisticated changes, including chimeric (strept)avidins, topology
      rearrangements and stitching of non-natural amino acids into the active sites. In
      this review, we highlight the current status in genetically engineered
      (strept)avidins and illustrate their versatility as advanced tools in the
      multiple fields of modern bioscience, medicine and nanotechnology.

PMID- 17433847
TI  - Catalytic efficiency and kcat/KM: a useful comparator?
AB  - The ratio k(cat)/K(M)--often referred to as the "specificity constant"--is a
      useful index for comparing the relative rates of an enzyme acting on alternative,
      competing substrates. However, an alternative description, "catalytic
      efficiency", is frequently used, and on occasions misused, to compare the
      reactivity of two enzymes acting on the same substrate. Here, we highlight the
      pitfalls in using k(cat)/K(M) to compare the catalytic effectiveness of enzymes.

PMID- 17433848
TI  - Info-disruption: pollution and the transfer of chemical information between
      organisms.
AB  - Many organisms use subtle chemical cues not only to find partners and food, but
      also to sense the presence of natural enemies and to avoid predation. As we
      discuss here, an increasing number of studies now show that low, non-toxic
      concentrations of chemicals, ranging from heavy metals and pesticides to
      seemingly harmless substances such as surfactants, can disrupt the transfer of
      chemical information, inducing maladaptive responses in both the signaller and
      the receiver. Similar to endocrine disruptors, these 'info disruptors' form a new
      class of chemical threats, which could have far-reaching implications for
      ecosystem functioning and conservation management.

PMID- 17433849
TI  - In vivo reflectance confocal microscopy of mycosis fungoides: A preliminary
      study.
AB  - BACKGROUND: Mycosis fungoides (MF) is a diagnostic challenge, frequently needing
      multiple and sequential biopsies to establish the diagnosis. OBJECTIVE: Our aim
      was to evaluate lesions suggestive of MF using in vivo reflectance confocal
      microscopy (RCM) and to correlate confocal features with histopathologic
      findings. METHODS: A total of 8 lesions from 7 patients either with a history of
      biopsy-proven MF or with lesions clinically suggestive of MF were imaged with RCM
      followed by a skin punch biopsy. These 8 lesions were confirmed to be MF by
      histopathology: patch type (n = 3), plaque type (n = 4), and tumor type (n = 1).
      RESULTS: Under RCM, epidermal findings in patch lesions were subtle, as on
      histopathology, while the most prominent changes were observed in plaque type MF.
      At the level of the epidermis, weakly refractile oval to round structures within
      the spinous layer were observed in all MF lesions, but were difficult to
      distinguish from surrounding keratinocytes; these structures corresponded to
      epidermotropic lymphocytes on histopathology. In plaque-type lesions, vesicle
      like dark spaces filled with collections of monomorphous weakly refractile oval
      to round cells were clearly elucidated by RCM; these structures corresponded to
      Pautrier's microabscesses on histopathology. RCM was also able to demonstrate
      spongiosis in the MF lesions, with findings of epidermal architectural disarray,
      areas with thickened and blurred intercellular demarcations, and epidermal cells
      with elongated nuclei. At the dermoepidermal junction, the basal cells
      surrounding the dermal papillae appeared as only faintly refractile rings on RCM.
      This feature corresponded with histopathologic findings of basal layer
      infiltration by tumor cells with permeation of rete ridges, thus, obscuring the
      dermoepidermal interface. Examination of the dermis under RCM for all the MF
      lesions showed weakly refractile structures, but was limited by loss of detail
      and contrast below the dermoepidermal junction. LIMITATIONS: Because of limited
      imaging depth, RCM did not visualize dermal infiltration by tumor cells in tumor
      type MF. Epidermotropic lymphocytes appeared weakly refractile under RCM and were
      difficult to distinguish from surrounding keratinocytes as a result of minimal
      difference in contrast. Other limitations on RCM include some similarity in
      findings with spongiotic and lichenoid dermatitides, and an inability to
      distinguish specific cell types. Moreover, this study did not address the
      inherent heterogeneity of MF lesions, but was primarily focused on correlating
      RCM and hematoxylin-eosin histopathology of the included cases. CONCLUSION:
      Features correlating well to histopathology are observed on RCM of MF lesions;
      however, the specificity of these findings needs to be assessed.

PMID- 17433850
TI  - Thymoma-associated multiorgan autoimmunity: a graft-versus-host-like disease.
AB  - Graft-versus-host disease (GVHD) is a T cell-mediated disease seen most commonly
      after hematopoietic stem cell transplantation. Rarely, a GVHD-like disease can be
      seen in patients with malignant thymoma. We describe a 50-year-old man with
      malignant thymoma who developed skin, liver, and intestinal manifestations
      similar to that seen in GVHD. We also review other reported cases of GVHD-like
      manifestations in the setting of thymoma and propose "thymoma-associated
      multiorgan autoimmunity" as a name for this novel disease. Specifically, thymoma
      associated multiorgan autoimmunity is defined as a disease of the liver,
      intestine, or skin, which on histopathology resembles GVHD but is seen in the
      setting of malignant thymoma and not after hematopoietic stem cell
      transplantation.

PMID- 17433851
TI  - Design, synthesis and biological evaluation of new oligopyrrole carboxamides
      linked with tricyclic DNA-intercalators as potential DNA ligands or topoisomerase
      inhibitors.
AB  - In the context of the design and synthesis of minor groove binding and
      intercalating DNA ligands some new oligopyrrole carboxamides were synthesized.
      These hybrid molecules (combilexins) possess a variable and conformatively
      flexible spacer at the N-terminal end. As intercalating tricyclic systems
      acridone, acridine, anthraquinones and in a special case iminostilbene terminate
      the N-terminal end of the pyrrole chain. The cytotoxicity was examined by the NCI
      antitumor screening, furthermore, biophysical as well as biochemical studies were
      performed in order to get some information about the DNA binding properties and
      topoisomerase inhibition effect of this new series of molecules.

PMID- 17433852
TI  - Radioactivity in the environment around past radium and uranium mining sites of
      Portugal.
AB  - Measurements of ambient radiation doses and determination of radionuclide
      concentrations in mining waste and soils were performed in 60 areas of former
      radium and uranium mining. In several places, mining waste and low-grade uranium
      ore left on the surface contain radioactivity above regional background. Most of
      the former mining sites present no enhanced radionuclide concentrations. However,
      in the mining facilities where the radioactive ore was chemically extracted, mill
      tailings contain materials with elevated levels of radioactivity, up to 200 times
      the levels in unaffected soils of the region. Mud from neutralization ponds used
      to treat acid mine waters contains also elevated radionuclide concentrations.
      Furthermore, depending on the type of waste, the radioelement composition varies.
      Environmental rehabilitation measures shall take these differences into account
      in order to prevent in the long term the radioactive contamination of agriculture
      soils and water resources, and to ensure adequate radiological protection to the
      public and to the environment.

PMID- 17433853
TI  - Psychological treatment dropout among pathological gamblers.
AB  - Premature dropout from treatments for pathological gambling is potentially of
      significant importance, if it occurs before substantial progress has been made in
      addressing the problem. A systematic review of current research on dropout from
      psychological treatments for pathological gambling identified 12 studies from
      five countries. Dropout ranged from 14% to 50%, with a median of dropout 26%.
      Overall, 31% of the participants dropped out of treatment. Few studies
      distinguish between dropouts at different stages of participation. The evidence
      on specific variables that predict dropout is limited or inconsistent, and is
      characterised by a lack of a coherent, gambling-specific model and by
      methodological problems. Two studies that attempted to apply motivational and
      compliance-enhancing techniques were found. Both showed promising effects on
      reduction of dropout and improvement of short-term impact of treatment, but
      inconsistent results on longer-term outcomes were obtained. The review
      highlighted a need for more rigorous investigation of the extent of dropout and
      of variables associated with dropout from pathological gambling treatment
      programs. Further research on interventions to enhance retention and reduce
      dropout from psychological treatment is also required.

PMID- 17433854
TI  - Ultrasonic speed of sound dispersion imaging.
AB  - The feasibility for speed of sound dispersion (SOSD) imaging was investigated
      here. A through transmission new method for measuring the SOSD was utilized. With
      this method a long pulse comprising of two frequencies one being the double of
      the other is transmitted through the object and detected on its other side. SOSD
      projection images were obtained by scanning objects immersed in water using a
      raster mode utilizing a computerized scanning system. Using this approach SOSD
      projection images were obtained for solids and fluids as well as for a tissue
      mimicking breast phantom and an in vitro soft tissues phantom. The results
      obtained here, have clearly demonstrated the feasibility of SOSD projection
      imaging. SOSD may serve as a new contrast source and potentially may aid in
      breast diagnosis.

PMID- 17433855
TI  - Weekly paclitaxel and carboplatin against advanced transitional cell cancer after
      failure of a platinum-based regimen.
AB  - OBJECTIVE: Weekly administration of paclitaxel plus carboplatin is hypothesized
      to be an effective second-line treatment for advanced transitional cell cancer
      after failure of platinum-based regimen. In this phase 2 trial, we tested this
      hypothesis. PATIENTS AND METHODS: Patients with advanced transitional cell cancer
      who showed evidence of progressive or recurrent disease after methotrexate,
      vinblastine, doxorubicin, and cisplatin (MVAC) therapy were eligible for this
      study. Weekly paclitaxel (80mg/m(2)) and carboplatin (AUC 2) were administered on
      days 1, 8, 15, 22, 29, and 36; the cycle was repeated every 7 wk until disease
      progression or intolerable toxicity (maximum 18 doses). RESULTS: Thirty-five
      patients entered this study. Among the 31 patients who were assessable, 10 had an
      objective response (overall response rate: 32.3%, 95% confidence interval, 15.8
      48.7%). The median progression-free survival (PFS) and median survival times were
      3.7 and 7.9 mo, respectively. Among the 22 patients who received prior MVAC
      therapy for metastatic disease, 36% had an objective response; their median PFS
      and median survival times were 4.3 and 7.9 mo, respectively; neither survival
      time significantly differed from the survival time of those who received prior
      MVAC as adjuvant setting. Toxicities were mild except one toxic death due to
      neutropenic sepsis. CONCLUSIONS: Weekly paclitaxel plus carboplatin was a
      manageable, active second-line treatment for advanced transitional cell cancer
      after failure of platinum-based therapy.

PMID- 17433856
TI  - Editorial comment on: Weekly paclitaxel and carboplatin against advanced
      transitional cell cancer after failure of a platinum-based regimen.

PMID- 17433857
TI  - Photocatalytic degradation of phenol in aqueous solutions by Pr-doped TiO2
      nanoparticles.
AB  - Photocatalytic degradation of phenol in water was examined using Pr-doped TiO(2)
      nanoparticles. These photocatalysts were synthesized by an acid-peptized sol-gel
      method from titanium tetra-isopropoxide with different concentrations of Pr(III)
      dopant and calcination temperatures. Several tools such as XRD, BET surface area,
      SEM, and EDX, were used to evaluate particle structure, size distribution, and
      composition. The optical absorption properties of the prepared particles were
      also measured. Photocatalytic activity of the particles was studied in a batch
      reactor containing phenol solution with 400W UV irradiation. Parameters affecting
      photocatalytic process such as the catalyst crystallinity, light absorption
      efficiency, the dosage of catalyst, dopant and phenol concentrations were
      investigated. The Pr-doped TiO(2) showed high activity for photocatalytic
      degradation of phenol. The presence of Pr ions in the TiO(2) particles would
      cause a significant absorption shift towards the visible region. The degradation
      process was optimized using 1g/L Pr-doped TiO(2) with a Pr(III) concentration of
      0.072 mol% after 2h irradiation. It was shown that photodegradation followed a
      pseudo-first-order kinetics and the rate constant changed with phenol
      concentration.

PMID- 17433858
TI  - Characterization of a novel mouse brain gene (mbu-1) identified by digital
      differential display.
AB  - Using in silico approaches, we cloned a novel mouse gene (mbu-1) that was
      strictly expressed in the central nervous system. mbu-1 was first identified as
      an EST after carrying out digital differential display for unigene libraries from
      various mouse tissues. The full-length cDNA sequence was obtained by extending
      the ends of EST by RACE. The cDNA sequence was 2611 bp long and contained an ORF
      of 597 AA. A positive cis-acting region was found in the neuroblastomaxglioma
      hybrid, NG108-15, and in human embryonic kidney HEK293 cell lines. RT-PCR and in
      situ hybridization analysis showed that the mbu-1 gene was only expressed in the
      brain and spinal cord during the embryonic stages, and throughout all regions of
      the adult brain, showing higher levels in the hippocampus and hypothalamus.

PMID- 17433859
TI  - Isoprenoid biosynthesis authenticates the classification of the green alga
      Mesostigma viride as an ancient streptophyte.
AB  - Land plants harbor two essential and completely different metabolic pathways for
      isoprenoid synthesis. The cytosolic mevalonate pathway (MVA) is shared with
      heterotrophic eukaryotes, whereas the plastidial 2-C-methyl-d-erythritol 4
      phosphate (MEP) pathway has a cyanobacterial origin and was recruited after
      primary endosymbiosis. Terrestrial plants and green algae have a common
      evolutionary ancestry, but biochemical as well as genome analyses indicate that
      the cytosolic MVA pathway is generally absent from Chlorophyta. We investigated
      the distribution of genes for both pathways in the green alga Mesostigma viride,
      a key species at the basis of streptophycean (charophycean green algae, land
      plant) evolution. Ten of altogether twelve generally weakly expressed genes for
      isoprenoid biosynthesis, including three for the cytosolic MVA pathway, were
      amplified using a reverse transcription PCR approach with individually designed
      degenerate primers. Two full length cDNA clones for the first enzyme of the MVA
      pathway (HMGS) were additionally established from the charophycean green alga
      Chara vulgaris by library screening. The presence of the MVA pathway in these
      advanced green algae indicates a universal distribution among Streptophyta, and
      our phylogenetic HMGS analyses substantiate the recent classification of
      Mesostigma basal to charophytes and land plants. We identified each of the five
      cytosolic MVA genes/cDNAs in the genome of the rhodophyte Galdieria sulphuraria
      and, furthermore, amplified four of them from the glaucophyte Cyanophora
      paradoxa. Our data indicate that the MVA pathway is a characteristic trait of
      Plantae in general and propose that it was specifically lost in a common ancestor
      of Chlorophyta.

PMID- 17433860
TI  - Analysis of tRNA abstract shapes of precursor/derivative amino acids in Archaea.
AB  - Wong's theory of the genetic code's origin states that because of historical
      constraints, codon assignment depends on the relation between precursor and
      derivative amino acids, a result of the coevolutionary process between amino
      acids' biosynthetic pathways and tRNAs. Based on arguments supporting the
      assumption that natural selection favors more stable and thus functionally
      constrained structures, we tested whether precursor and derivative tRNAs are
      equally evolved by measuring their structural parameters, thermostability and
      molecular plasticity. We also estimated the extent to which precursor and
      derivative tRNAs differ within Archaea. We used Archaea sequences of both
      precursor and derivative tRNAs in order to examine the plastic repertoires or
      sets of suboptimal structures at a defined free energy interval. We grouped
      secondary structures according to their helix nesting and adjacency using
      abstract shapes analysis. This clustering enabled us to infer a consensus
      sequence for all shapes that fit the clover leaf secondary structure [Giegerich,
      R., et al., Nucleic Acids Res 2004; 32 (16): 4843-51.]. This consensus sequence
      was then folded in order to retrieve a set of suboptimal structures. For each
      pair of precursor and derivative tRNAs, we compared these plastic repertoires
      based on the number of secondary structures, the thermostability of the minimum
      free energy structure and two structural parameters (base pair propensity (P) and
      mean length of helical stem structures (S)), which were measured for every
      representative secondary structure [Schultes, E.A., et al., J Mol Evol 1999; 49
      (1): 76-83.]. We found that derivative tRNAs have fewer numbers of shapes, higher
      thermostability and more stable parameters than precursor tRNAs, a fact in full
      agreement with Wong's coevolution theory of the genetic code.

PMID- 17433861
TI  - Using organizational assessment as a tool for program change.
AB  - Organizational functioning within substance abuse treatment organizations is
      important to the transfer of research innovations into practice. Programs should
      be performing well for new interventions to be implemented successfully. This
      study examined the characteristics of treatment programs that participated in an
      assessment and training workshop designed to improve organizational functioning.
      The workshop was attended by directors and clinical supervisors from 53 community
      based treatment units in a single state in the Southwest. Logistic regression
      analysis was used to examine attributes related to program-level decisions to
      engage in a structured process for making organizational changes. Findings showed
      that programs with higher needs and pressures, more limited institutional
      resources, and poorer ratings on staff attributes and organizational climate were
      the most likely to engage in a change strategy. Furthermore, organizations with
      greater staff consensus (i.e., smaller standard deviations) on ratings of
      organizational climate were also more likely to engage in change.

PMID- 17433862
TI  - Linking the elements of change: Program and client responses to innovation.
AB  - The process of innovation adoption was investigated using longitudinal records
      collected from a statewide network of almost 60 treatment programs over a 2-year
      period. Program-level measures of innovation adoption were defined by averaged
      counselor ratings of program training needs and readiness, organizational
      functioning, quality of a workshop training conference, and adoption indicators
      at follow-up. Findings showed that staff attitudes about training needs and past
      experiences are predictive of their subsequent ratings of training quality and
      progress in adopting innovations a year later. Organizational climate (clarity of
      mission, cohesion, openness to change) is also related to innovation adoption. In
      programs that lack an open atmosphere for adopting new ideas, it was found that
      counselor trial usage is likely to be attenuated. Most important was evidence
      that innovation adoption based on training for improving treatment engagement was
      significantly related to client self-reports of improved treatment participation
      and rapport recorded several months later.

PMID- 17433863
TI  - Influence of organizational functioning on client engagement in treatment.
AB  - This study focused on the relationship between organizational functioning factors
      measured in a staff survey using the Texas Christian University (TCU)
      Organizational Readiness for Change assessment and client-level engagement
      measured by the TCU Client Evaluation of Self and Treatment in drug treatment
      programs. The sample consisted of 531 clinical and counseling staff and 3,475
      clients from 163 substance abuse treatment programs located in nine states from
      three regional Addiction Technology Transfer Centers. Measures of client
      engagement in treatment (rapport, satisfaction, and participation) were shown to
      be higher in programs with more positive staff ratings of organizational
      functioning. In particular, these programs had fewer agency needs and more
      favorable ratings for their resources, staff attributes, and climate. These
      findings help establish the importance of addressing organizational factors as
      part of an overall strategy for improving treatment effectiveness.

PMID- 17433864
TI  - B1 SINEs in different rodent families.
AB  - B1 SINEs were studied in 22 families covering all major rodent lineages. The
      number of B1 copies considerably varies, from 1 x 10(4) in Geomyidae to 1 x 10(6)
      in Myodonta. B1 sequences can be divided into three main structural variants: B1
      with a 20-bp tandem duplication (found in Gliridae, Sciuridae, and Aplodontidae),
      B1 with a 29-bp duplication (found in other families), and proto-B1 without
      duplication (pB1). These variants can be further subdivided according to their
      characters, including specific 7-, 9-, or 10-bp deletions. Different B1
      subfamilies predominate in different rodent families. The analysis of B1 variants
      allowed us to propose possible pathways for the evolution of this SINE in the
      context of rodent evolution.

PMID- 17433865
TI  - The pathogenesis of atherosclerosis in autoimmune rheumatic diseases: roles of
      inflammation and dyslipidemia.
AB  - As patients with autoimmune rheumatic diseases live longer due to improved
      therapies and preventive measures, death and disability from atherosclerosis,
      particularly myocardial infarcts, are increasing. The relative risks for
      atherosclerosis vary from approximately 1.6 in ankylosing spondylitis and
      psoriatic arthritis to 3.0 in rheumatoid arthritis (RA), and 6.0 in systemic
      lupus erythematosus (SLE). Increased risks are found when analyzed by
      atherosclerotic events, causes of death, or surrogate measures of
      atherosclerosis, such as carotid artery plaque, intimal-media thickness, or
      coronary artery calcification. At all ages among adults, atherosclerosis is
      increased in patients with SLE or RA compared to healthy controls. For example,
      in women with SLE under the age of 40 years, approximately 13% have carotid
      plaque compared to 2% of controls; over age 59 the percentages are 71 and 45,
      respectively. For patients with RA, prevalence is 7% under the age of 40 in
      patients compared to zero in controls; over 59 years the prevalences are 80% and
      44%, respectively. In this review we will discuss the mechanisms involved as well
      as an overview of the natural history in pathobiology.

PMID- 17433866
TI  - Quantifying incoherence in speech: an automated methodology and novel application
      to schizophrenia.
AB  - Incoherent discourse, with a disjointed flow of ideas, is a cardinal symptom in
      several psychiatric and neurological conditions. However, measuring incoherence
      has often been complex and subjective. We sought to validate an objective,
      intrinsically reliable, computational approach to quantifying speech incoherence.
      Patients with schizophrenia and healthy control volunteers were administered a
      variety of language tasks. The speech generated was transcribed and the coherence
      computed using Latent Semantic Analysis (LSA). The discourse was also analyzed
      with a standard clinical measure of thought disorder. In word association and
      generation tasks LSA derived coherence scores were sensitive to differences
      between patients and controls, and correlated with clinical measures of thought
      disorder. In speech samples LSA could be used to localize where in sentence
      production incoherence occurs, predict levels of incoherence as well as whether
      discourse "belonged" to a patient or control. In conclusion, LSA can be used to
      assay disordered language production so as to both complement human clinical
      ratings as well as experimentally parse this incoherence in a theory-driven
      manner.

PMID- 17433867
TI  - Auditory toxicity after parotid irradiation.

PMID- 17433868
TI  - B cells and the BAFF/APRIL axis: fast-forward on autoimmunity and signaling.
AB  - B-cell activation factor from the tumor necrosis factor family (BAFF) is a key
      survival factor during B-cell maturation -- a delicate immune checkpoint for B
      cells. Excessive BAFF production at this stage corrupts B-cell tolerance and
      leads to autoimmunity. Elevated serum BAFF levels have been detected in some
      patients suffering from various autoimmune conditions. The positive outcomes of
      currently ongoing clinical trials using BAFF-neutralising agents confirm that
      this factor plays a major pathological role in rheumatoid arthritis and in
      systemic lupus erythematosus. Almost a decade after its discovery, BAFF continues
      to occupy the main stage in Immunology, with more than one hundred BAFF-related
      articles published per year. In recent years, our understanding of cell signaling
      and autoimmune mechanisms in this system have seen major advances, refining new
      possibilities for therapeutic intervention.

PMID- 17433869
TI  - Cytokines and T-cell homeostasis.
AB  - Homeostasis of T cells can be defined as the ability of the immune system to
      maintain normal T-cell counts and to restore T-cell numbers following T-cell
      depletion or expansion. These processes are governed by extrinsic signals, most
      notably cytokines. Two members of the common gamma chain family of cytokines,
      interleukin (IL)-7 and IL-15, are central to homeostatic proliferation and
      survival of mature CD4(+) and CD8(+) T cells. Recent evidence suggests that other
      cytokines, including IL-2, IL-10, IL-12, interferons and TGF-beta, as well as the
      transcription factors T-bet and eomesodermin all play important but different
      roles at distinct stages of T-cell homeostasis.

PMID- 17433870
TI  - New twists of T cell fate: control of T cell activation and tolerance by TGF-beta
      and NFAT.
AB  - Protective and pathogenic immune responses were initially thought to be
      determined by the differentiation of naive T cells into Th1 and Th2 effector
      subsets and the immunosuppressive activity of thymic-derived regulatory T cells.
      It is now clear that naive T cells can also differentiate into 'induced'
      regulatory T cells or inflammatory T cells that secrete IL-17. These divergent T
      cell subsets have opposing functions in imparting inflammation or tolerance, yet
      both developmental programs are controlled by the pluripotent cytokine
      transforming growth factor beta and the transcription factor NFAT. Recent
      findings have begun to shed light on the mechanisms by which TGF-beta and NFAT
      integrate multiple signaling inputs to determine the direction of naive T-cell
      differentiation.

PMID- 17433871
TI  - Delivering the kiss of death: progress on understanding how perforin works.
AB  - Killer lymphocytes release perforin and granzymes from cytotoxic granules into
      the immunological synapse to destroy target cells as a critical mechanism in the
      defense against viruses and cancer. Perforin, a Ca(2+)-dependent pore-forming
      protein that multimerizes in membranes, delivers granzymes into the target cell
      cytosol. The original model for perforin (acting by forming a cell membrane
      channel through which granzymes pass) does not fit the experimental data.
      Recently, an alternative model has been proposed that involves active target cell
      collaboration with perforin to deliver granzymes and direct the target cell to an
      apoptotic, rather than necrotic, death.

PMID- 17433872
TI  - PD-1 and its ligands in T-cell immunity.
AB  - The past year has seen significant advances in our understanding of the critical
      roles of negative immunoregulatory signals delivered by the programmed death 1
      (PD-1)-PD-1 ligand (PD-L) pathway in regulating T-cell activation and tolerance.
      Emerging evidence indicates that PD-Ls play an essential role on dendritic cells
      (DCs), both directly during DC-T cell interactions and indirectly through
      signaling into the DC. Recent studies point to a novel role for PD-L1 in
      maintaining tissue tolerance. Finally, PD-1 has recently been shown to be highly
      expressed on exhausted T cells during chronic viral infection, and blockade of PD
      1 or PD-L1 can revive exhausted T cells, enabling them to proliferate and produce
      effector cytokines.

PMID- 17433873
TI  - Requirements for CD8 T-cell priming, memory generation and maintenance.
AB  - Immunological memory is characterized by the ability to provide protection from
      secondary exposure to pathogens. CD8(+) memory T cells provide protection from
      cell-associated antigens owing to their elevated frequency, rapid response and
      localization to sites of infection. Events occurring during primary exposure to
      antigen can impact not only the magnitude and quality of the initial cytotoxic T
      lymphocyte response but also the efficacy and longevity of the ensuing CD8(+)
      memory pool. Recent advances shed light on the relative roles of TCR signals and
      environmental cues in guiding the development of CD8(+) effector T cells into
      CD8(+) memory T cells and supporting CD8(+) memory T-cell maintenance.

PMID- 17433874
TI  - The T cell repertoire in infection and vaccination: implications for control of
      persistent viruses.
AB  - Most currently available vaccines target acute infectious agents such as polio,
      smallpox and influenza virus. The development of vaccines to persistent
      infectious agents has proven much more difficult. Although it is possible to
      generate T cell responses to such viruses, these responses are currently unable
      to prevent the establishment of infection, and immune control may be lost during
      the chronic phase. Recent advances have increased our understanding of the
      interactions between persistent viruses and the available T cell repertoire, and
      will guide approaches to the generation and maintenance of an 'ideal' T cell
      response.

PMID- 17433875
TI  - Toll-like receptors and innate immunity in B-cell activation and antibody
      responses.
AB  - It has been known for almost 30 years that mouse B cells proliferate and
      differentiate to antibody-secreting cells when stimulated by microbial products
      such as lipopolysaccharide or CpG-containing DNA, but the relevance of these
      polyclonal responses remained elusive until recently. A breakthrough in the field
      has been the discovery of endosomal Toll-like receptors in B cells and their role
      in the production of autoantibodies. Since then, several reports have extended
      the role of Toll-like receptors in B-cell responses to thymus-independent and
      thymus-dependent antigens, and in antibody class switch in lymphoid and
      extralymphoid tissues. Considering the complexity of the system it is perhaps not
      surprising that the literature contains some contradictory findings. However, the
      scientific fecundity in this rapidly evolving field will probably give rise to
      discoveries that could be translated into more effective vaccines and
      immunotherapies.

PMID- 17433876
TI  - Single-cell dynamics of T-cell priming.
AB  - The recent application of in vivo imaging to characterize the dynamics of T-cell
      activation by dendritic cells (DCs) has reshaped long-held beliefs of how
      adaptive immune responses are initiated. However, to improve our fundamental
      understanding, these new observations must be synthesized with the diverse
      theories and paradigms in the field, many of which were established before the
      advent of the cutting-edge techniques in a modern immunologist's toolbox. A
      number of factors have been investigated that combine to determine the ability of
      the DC to activate a naive T cell: the rules that govern the ability of a T cell
      to find antigen-bearing DCs; the parameters that define the dose and quality of
      the antigenic signal; and the mechanisms used by the T cell to interpret a given
      antigenic signal. Considering T-cell activation to be determined by the sum of
      interdependent factors might allow us to integrate seemingly disparate
      observations and hypotheses and to formulate testable predictions for further
      experimentation.

PMID- 17433877
TI  - GABA(B) receptors: synaptic functions and mechanisms of diversity.
AB  - GABA(B) receptors are the G-protein-coupled receptors for GABA, the main
      inhibitory neurotransmitter in the mammalian central nervous system. They are
      implicated in a variety of neurological and psychiatric disorders. With the
      cloning of GABA(B) receptors ten years ago, substantial progress was made in our
      understanding of this receptor system. Here, we review current concepts of
      synaptic GABA(B) functions and present the evidence that points to specific roles
      for receptor subtypes. We discuss ultrastructural studies revealing that most
      GABA(B) receptors are located remote from GABAergic terminals, which raises
      questions as to when such receptors become activated. Finally, we provide
      possible explanations for the perplexing situation that GABA(B) receptor subtypes
      that have indistinguishable properties in vitro generate distinct GABA(B)
      responses in vivo.

PMID- 17433878
TI  - Preconditioning injury-induced neurite outgrowth of adult rat sensory neurons on
      fibronectin is mediated by mobilisation of axonal alpha5 integrin.
AB  - A preconditioning sciatic nerve crush promotes the capacity of adult sensory
      neurons to regenerate following a subsequent injury to their axons. The increase
      in regeneration is detected in cultures of dissociated neurons, as an earlier and
      enhanced rate of neurite elongation. We compare neurotrophin-stimulated neurite
      outgrowth from sensory neurons on laminin and fibronectin. There is a poor
      response of sensory neurons to fibronectin in comparison to laminin, but this is
      enhanced by a preconditioning lesion to the sciatic nerve 7 days prior to
      culture. By using specific integrin-binding fibronectin fragments and function
      blocking antibodies, we demonstrate that the enhanced preconditioned neurite
      outgrowth on fibronectin is largely mediated by alpha5beta1 integrin.
      Preconditioning injury alter the subcellular localisation of alpha5 integrin in
      preconditioned neurites. We show that alpha5 integrin localises to adhesion
      complexes in the growth cone and neurites of preconditioned neurons, but not
      control neurons.

PMID- 17433879
TI  - The effects of brain tissue decomposition on diffusion tensor imaging and
      tractography.
AB  - There have been numerous high resolution diffusion tensor imaging studies in
      fixed animal brains, but relatively few studies in human brains. While animal
      tissues are generally fixed pre-mortem or directly postmortem, this is not
      possible for human tissue, therefore there is always some delay between death and
      tissue fixation. The elapsed time between death and tissue fixation, the
      postmortem interval (PMI), will most likely adversely affect the tissue's
      diffusion properties. We studied the effects of PMI on the diffusion properties
      of rodent brain. Eight mice were euthanized and the brains (kept in the skull)
      were placed in formalin at PMIs of 0, 1, 4 and 14 days. Post fixation they were
      placed in a solution of GdDTPA and phosphate buffered saline. Brains were scanned
      with a 3D EPI DTI sequence at 4.7T. DTI data were processed to generate apparent
      diffusion coefficient (ADC) and fractional anisotropy (FA) maps. DTI tractography
      was also performed. The temporal changes in regional ADC and FA values were
      analyzed statistically using a one-way ANOVA, followed by individual Student's T
      tests. Regional FA and ADC of gray and white matter decreased significantly with
      time (p<0.05). DTI tractography showed a decrease in the number and coherence of
      reconstructed fiber pathways between PMIs 0 and 14. Elapsed time between death
      and tissue fixation has a major effect upon the brain's diffusion properties and
      should be born in mind when interpreting fixed brain DTI.

PMID- 17433880
TI  - Human cortical circuits for central executive function emerge by theta phase
      synchronization.
AB  - Dynamic networking of brain regions is suggested to be one of the key factors
      involved in various brain computations. Central executive function typically
      requires instantaneous coordination among the medial prefrontal regions and other
      distant regions, depending on the on-going task situation. In human scalp
      recorded electroencephalography (EEG), the medial prefrontal area is estimated to
      be the current source of the theta rhythm, while there is no direct evidence that
      the theta rhythm is involved in the dynamic networking of central executive
      circuits. Here we hypothesize that the central executive circuit over the
      prefrontal and task-related cortices is dynamically linked by theta
      synchronization. By using simultaneous functional magnetic resonance imaging
      (fMRI) and EEG, we elucidated cortical circuits emerging with theta phase
      synchronization during free pacing repeated subtraction. Theta phase
      synchronization in the scalp EEG was found to emerge at two major clusters of
      electrode pairs, between the right frontal and left parietal sites and between
      the frontal and right parietal sites. The phase synchronization of two clusters
      is accompanied by fMRI responses in the cortical regions responsible for central
      executive function, working memory, visual imagery and cognitive action sequence.
      Here we report the first evidence that theta phase synchronization dynamically
      coordinates the central executive circuits, including the medial prefrontal
      cortex and relevant cortical regions.

PMID- 17433882
TI  - Static knee alignment and its association with radiographic knee osteoarthritis.

PMID- 17433881
TI  - Impulsivity and chronic stress are associated with amphetamine-induced striatal
      dopamine release.
AB  - A challenging question that continues to plague the field of addiction is why
      some individuals are more vulnerable for substance use disorders than others.
      Several important risk factors for substance abuse have been identified in
      clinical studies, including trait impulsivity and environmental stress. However,
      the neurobiological mechanisms that underlie the relationships remain poorly
      understood. The purpose of this study was to examine associations among
      impulsivity, stress, and striatal dopamine (DA) responses to amphetamine (AMPH)
      in humans. Forty healthy M, F adults, ages 18-29 years, completed self-report
      measures of trait impulsivity, life events stress, and perceived stress. Subjects
      subsequently underwent two consecutive 90-min positron emission tomography (PET)
      studies with high specific activity [11C]raclopride. The first scan was preceded
      by an intravenous injection of saline; the second was preceded by 0.3 mg/kg AMPH.
      Findings showed that high impulsivity was associated with blunted right ventral
      striatal DA release. However, effects were modified by a significant interaction
      with life events stress. Dopamine release was greater in low vs. high impulsivity
      subjects under conditions of low or moderate stress. Under conditions of high
      stress, both groups had low DA release. Subjects with high impulsivity reported
      more pleasant effects with AMPH than subjects with low impulsivity. In contrast,
      stress was negatively associated with pleasant drug effects. No associations were
      observed between impulsivity or stress and cortisol responses to AMPH. The
      findings are consistent with notions that blunted DA responses represent an
      endophenotype for substance use disorders.

PMID- 17433884
TI  - The Australian Vascular Quality of Life Index (AUSVIQUOL): an improved clinical
      quality of life tool for peripheral vascular disease.
AB  - OBJECTIVES: To validate the Australian Vascular Quality of Life Index (AUSVIQUOL)
      as a quality of life (QOL) tool appropriate for peripheral vascular disease
      patients in the clinical setting. DESIGN: Cross-sectional study. MATERIALS: The
      study group consisted of 71 patients with vascular claudication of varying
      severity attending a tertiary hospital outpatient department. METHODS: The
      results of the AUSVIQUOL and Medical Outcomes Short Form Health Survey (SF-36)
      were compared through factor and regression analyses. A group of 12 patients was
      then reassessed to compare the reliability and internal consistency of the two
      indices. RESULTS: The AUSVIQUOL took less time to complete than the SF-36 (3.27 v
      10.79 min; p<0.0001) and fewer patients found the questions confusing (2% v 26%).
      The AUSVIQUOL was easier to administer and had a higher level of patient
      acceptance than the SF-36. The regression analysis showed that for each of the
      domains in the AUSVIQUOL there was a significant correlation with measures in the
      SF-36 (adjusted R-squared 0.420, 0.480 and 0.331). The AUSVIQUOL demonstrated a
      good level of internal consistency when compared to the SF-36 (Cronbach's alpha
      0.8702 vs 0.6307). CONCLUSION: In comparison with the SF-36, the AUSVIQUOL is an
      improved tool for the QOL assessment of patients with peripheral vascular disease
      in the clinical setting.

PMID- 17433885
TI  - Aromatic amino acid catabolism in trypanosomatids.
AB  - Trypanosomatids cause important human diseases, like sleeping sickness, Chagas
      disease, and the leishmaniases. Unlike in the mammalian host, the metabolism of
      aromatic amino acids is a very simple pathway in these parasites. Trypanosoma
      brucei and Trypanosoma cruzi transaminate the three aromatic amino acids, the
      resulting 2-oxo acids being reduced to the corresponding lactate derivatives and
      excreted. In T. cruzi, two enzymes are involved in this process: a tyrosine
      aminotransferase (TAT), which despite a high sequence similarity with the
      mammalian enzyme, has a different substrate specificity; and an aromatic L-2
      hydroxyacid dehydrogenase (AHADH), which belongs to the subfamily of the
      cytosolic malate dehydrogenases (MDHs), yet has no MDH activity. In T. cruzi
      AHADH the substitution of Ala102 for Arg enables AHADH to reduce oxaloacetate. In
      the members of the 2-hydroxyacid dehydrogenases family, the residue at this
      position is known to be responsible for substrate specificity. T. cruzi does not
      possess a cytosolic MDH but contains a mitochondrial and a glycosomal MDH; by
      contrast T. brucei and Leishmania spp. possess a cytosolic MDH in addition to
      glycosomal and mitochondrial isozymes. Although Leishmania mexicana also
      transaminates aromatic amino acids through a broad specificity aminotransferase,
      the latter presents low sequence similarity with TATs, and this parasite does not
      seem to have an enzyme equivalent to T. cruzi AHADH. Therefore, these closely
      related primitive eukaryotes have developed aromatic amino acid catabolism
      systems using different enzymes and probably for different metabolic purposes.

PMID- 17433886
TI  - New haemoglobin genotypes in Atlantic cod, Gadus morhua: possible relation with
      growth.
AB  - In a preliminary study, 121 individually tagged juvenile Atlantic cod (Gadus
      morhua) were classified according to their haemoglobin genotypes into four
      groups, i.e., two main haemoglobin genotypes [Hb-I(1/2), Hb-I(2/2)] and two sub
      types [Hb-I(1/2b), Hb-I(2/2b)], and reared for 3 months at 10 degrees C, 13
      degrees C and T-step (fish reared at 16 degrees C and then subsequently moved to
      13 and later to 10 degrees C). Overall growth rates across temperatures were 10%
      and 19% higher in the Hb-I(2/2b), Hb-I(1/2b) sub-types compared to corresponding
      Hb-I(2/2) and Hb-I(1/2) main types, respectively. Individual growth rate
      trajectories varied between the genotypes at all temperatures studied. Our study
      indicates that under certain environmental conditions higher growth in the two
      sub-types compared to the main genotypes could be expected. This may indicate
      difference in other physiological characters not studied here, but seen in
      previous studies, i.e., oxygen affinity and competitive performance.

PMID- 17433887
TI  - Nutritional responses to different diet quality in the subterranean rodent
      Ctenomys talarum (tuco-tucos).
AB  - Nutritional response to different diet quality was examined in the subterranean
      rodent Ctenomys talarum (tuco-tuco). Animals maintained in captive conditions
      were fed with three plant species that differed in their fibre content. Tuco
      tucos showed the ability to perform adjusts in short time lapse in response to
      diet quality; food ingestion, egestion and feces ingestion changed in animals
      under different plant species diets. Time budget, mainly time devoted to feeding
      and activity accompanied such changes. Coprophagy was practiced along the day and
      night following the arrhythmic activity pattern found for this species. Feces
      reingestion was not associated to resting. Furthermore, it was observed during
      fresh food ingestion, being pellets chewed. Soft and hard feces differed in
      morphological and nutritional characteristics.

PMID- 17433888
TI  - Uric acid as a prognostic marker in acute heart failure--new expectations from an
      old molecule.

PMID- 17433889
TI  - Antibiotics for the treatment of asthma.
AB  - Infection with Chlamydophila pneumoniae or Mycoplasma pneumoniae has been linked
      to asthma. There is evidence to suggest that persistent infection with these
      organisms might lead to an increase in the severity of asthma. beta-Lactam
      antibiotics have not been shown to be beneficial in the treatment of asthma but
      several studies have indicated that macrolides and related antibiotics might be
      useful both for the treatment of chronic asthma and for acute exacerbations.
      However, these observations need to be confirmed in further studies. It is not
      clear whether any effect that these antibiotics has is a result of antimicrobial
      actions against organisms such as C. pneumoniae or whether it is due to their
      anti-inflammatory action.

PMID- 17433891
TI  - Lexical ambiguity in sentence comprehension.
AB  - An event-related fMRI paradigm was used to investigate brain activity during the
      reading of sentences containing either a lexically ambiguous word or an
      unambiguous control word. Higher levels of activation occurred during the reading
      of sentences containing a lexical ambiguity. Furthermore, the activated cortical
      network differed, depending on: (1) whether the sentence contained a balanced
      (i.e., both meanings equally likely) or a biased (i.e., one meaning more likely
      than other meanings) ambiguous word; and, (2) the working memory capacity of the
      individual as assessed by reading span. The findings suggest that encountering a
      lexical ambiguity is dealt with by activating multiple meanings utilizing
      processes involving both hemispheres. When an early interpretation of a biased
      ambiguous word is later disambiguated to the subordinate meaning, the superior
      frontal cortex activates in response to the coherence break and the right
      inferior frontal gyrus and the insula activate, possibly to suppress the
      incorrect interpretation. Negative correlations between reading span scores and
      activation in the right hemisphere for both types of ambiguous words suggest that
      readers with lower spans are more likely to involve show right hemisphere
      involvement in the processing of the ambiguity. A positive correlation between
      reading span scores and insula activation appearing only for biased sentences
      disambiguated to the subordinate meaning indicates that individuals with higher
      spans were more likely to initially maintain both meanings and as a result had to
      suppress the unintended dominant meaning.

PMID- 17433892
TI  - A special role for the right hemisphere in metaphor comprehension? ERP evidence
      from hemifield presentation.
AB  - It has been suggested that the right hemisphere (RH) has a privileged role in the
      processing of figurative language, including metaphors, idioms, and verbal humor.
      Previous experiments using hemifield visual presentation combined with human
      electrophysiology support the idea that the RH plays a special role in joke
      comprehension. The current study examines metaphoric language. Event-related
      potentials (ERPs) were recorded as healthy adults read English sentences that
      ended predictably (High-cloze Literals), or with a plausible but unexpected word
      (Low-cloze Literals and Low-cloze Metaphoricals). Sentence final words were
      presented in either the left or the right visual hemifield. Relative to High
      cloze Literals, Low-cloze Literals elicited a larger N400 component after
      presentation to both the left and the right hemifield. Low-cloze Literals also
      elicited a larger frontal positivity following the N400, but only with
      presentation to the right hemifield (left hemisphere). These data suggest both
      cerebral hemispheres can benefit from supportive sentence context, but may
      suggest an important role for anterior regions of the left hemisphere in the
      selection of semantic information in the face of competing alternatives. Relative
      to Low-cloze Literals, Low-cloze Metaphoricals elicited more negative ERPs during
      the timeframe of the N400 and afterwards. However, ERP metaphoricity effects were
      very similar across hemifields, suggesting that the integration of metaphoric
      meanings was similarly taxing for the two hemispheres, contrary to the
      predictions of the right hemisphere theory of metaphor.

PMID- 17433893
TI  - The interaction of discourse context and world knowledge in online sentence
      comprehension. Evidence from the N400.
AB  - In an ERP experiment we investigated how the recruitment and integration of world
      knowledge information relate to the integration of information within a current
      discourse context. Participants were presented with short discourse contexts
      which were followed by a sentence that contained a critical word that was correct
      or incorrect based on general world knowledge and the supporting discourse
      context, or was more or less acceptable based on the combination of general world
      knowledge and the specific local discourse context. Relative to the critical word
      in the correct world knowledge sentences following a neutral discourse, all other
      critical words elicited an N400 effect that began at about 300 ms after word
      onset. However, the magnitude of the N400 effect varied in a way that suggests an
      interaction between world knowledge and discourse context. The results indicate
      that both world knowledge and discourse context have an effect on sentence
      interpretation, but neither overrides the other.

PMID- 17433895
TI  - The effects of masseter muscle paralysis on facial bone growth.
AB  - BACKGROUND: Understanding the effects of muscle function on facial bone growth
      may help us treat children with facial anomalies. Facial bone growth is known to
      be a result of both genetic and epigenetic influences. One of the main epigenetic
      factors controlling growth is thought to be muscle action. The purpose of this
      study was to establish a model of single facial muscle paralysis and to identify
      the effects masseter muscle paralysis has on mandible and zygoma growth. METHODS:
      Twenty New Zealand white rabbits were divided into control, paralysis, and sham
      groups. Masseter muscle paralysis was achieved with botulinum toxin A (BTX).
      Computed tomographic and single-photon emission computed tomography (SPECT) scans
      and cephalometric measurements were performed. Masseter weights and mandible and
      zygoma volumes, shapes, and metabolism were measured. RESULTS: Eighteen animals
      completed the study. Significant decreases in zygoma and mandible volumes with
      minimal changes in shape were seen on the paralyzed sides. SPECT showed a
      decrease in bone production in both zygomas and mandibles on the paralyzed sides.
      CONCLUSIONS: An animal model has been created in which the effects of single
      muscle paralysis on bone growth can be studied. Masseter muscle function may be
      responsible in maintaining mandible and zygoma volume by controlling bone
      production. Masseter function alone has less influence on mandible and zygoma
      shape.

PMID- 17433898
TI  - Hyperhomocysteinemia and venous thrombosis.
AB  - It has been recognized, since the first description of the disease, that arterial
      and venous thrombosis are common in patients with homocysteinuria. Interest in
      the condition increased with reports from a large number of mainly retrospective
      studies showing that mildly elevated homocysteine levels are also associated with
      venous thromboembolism (VTE), thrombotic stroke, and peripheral vascular disease.
      This association is less strong when populations are studied prospectively.
      Vitamin supplementation, primarily with folic acid, and to a lesser degree with
      pyridoxine and vitamin B(12), is effective in reducing elevated levels of plasma
      homocysteine. Surprisingly, however, recent prospective intervention studies
      showed that despite lowering of the homocysteine level with such treatment, there
      was no impact on the risk of recurrence of venous or arterial disease.

PMID- 17433897
TI  - Epidemiology and risk factors for venous thrombosis.
AB  - Venous thrombosis, including deep vein thrombosis (DVT) and pulmonary embolism
      (PE), occurs at an annual incidence of about 1 per 1,000 adults. Rates increase
      sharply after about age 45 years, and are slightly higher in men than women in
      older age. Major risk factors for thrombosis, other than age, include exogenous
      factors such as surgery, hospitalization, immobility, trauma, pregnancy, and the
      puerperium and hormone use, and endogenous factors such as cancer, obesity, and
      inherited and acquired disorders of hypercoagulation. This review focuses on
      epidemiology of venous thrombosis and the general implications of this in patient
      management.

PMID- 17433899
TI  - Plasma coagulation factor levels in venous thrombosis.
AB  - High plasma levels of several coagulation factors have been described to be
      associated with an increased risk of venous thrombosis. However, the mechanisms
      underlying these associations, as well as those involved in the regulation of
      plasma levels of coagulation factors, are mostly unknown. Whether these factors
      should be included in the workup of patients with venous thrombosis remains to be
      determined. In this review, we discuss the present knowledge on the effects of
      plasma levels of coagulation factors on the development of venous thrombosis.
      Furthermore, we review recent findings and ideas on the mechanisms through which
      elevated plasma coagulation factor levels may influence thrombosis. Finally, we
      enter into the matter of the possible determinants of elevated plasma levels of
      coagulation factors.

PMID- 17433900
TI  - Predictive genetic variants for venous thrombosis: what's new?
AB  - Various pathways lead to the development of venous thrombosis. Risk factors are
      common and can be genetic or acquired. Since the identification of factor V
      Leiden and prothrombin 20210 G-->A, the field of genetic epidemiology has
      developed rapidly and many new genetic variants have been described in the past
      decade. However, the association with venous thrombosis is often unclear and
      conflicting results have been reported in various studies. The aim of this review
      is to describe these candidate predictors of venous thrombosis and to put these
      in perspective.

PMID- 17433901
TI  - Pregnancy failure and heritable thrombophilia.
AB  - Heritable thrombophilia is associated with an increased risk for pregnancy
      failure, defined as sporadic and recurrent miscarriage, late fetal loss, and
      other vascular pregnancy complications such as preeclampsia and intrauterine
      growth retardation. The pathogenesis is likely to include effects on trophoblast
      differentiation and not solely hypercoagulability. This is in line with the
      observation that most recurrent miscarriages occur early. Therapeutic options
      include aspirin as well as low-molecular-weight heparin. However, in women with
      heritable thrombophilia and unexplained recurrent pregnancy loss, evidence is not
      available as published trials have not used an adequate comparator (no treatment
      or placebo). Currently, randomized controlled trials with no treatment or placebo
      are being carried out and results should be awaited before implementing a
      potentially harmful intervention in pregnant women with heritable thrombophilia
      and a history of pregnancy failure. Both infertility and pregnancy failure are
      extremely distressing for couples with the desire to have children. Pregnancy
      failure comprises (recurrent) early miscarriage, as well as late pregnancy loss.
      The role of heritable thrombophilia in pregnancy failure is reviewed, with a
      focus on recurrent miscarriage, in terms of epidemiology, etiology, and potential
      therapeutic implications.

PMID- 17433902
TI  - Sex hormones and thrombosis.
AB  - There is compelling evidence that use of oral formulations of female hormone
      replacement and of the combined oral contraceptive induces a prothrombotic state.
      This translates to an increased thrombotic risk. Within the individual, the
      absolute risk is determined by the interaction between that induced by hormone
      use and heritable and acquired risk factors for thrombosis. Knowledge of the
      accumulating epidemiologic and clinical trial-derived data on this topic is
      essential for the delivery of evidence-based counseling in the clinical
      environment and is the subject of this review.

PMID- 17433903
TI  - Inherited thrombophilia in arterial disease: a selective review.
AB  - Thrombophilia may be defined as an acquired or congenital abnormality of
      hemostasis predisposing to thrombosis. Because arterial thrombosis is usually
      linked with classical risk factors such as smoking, hypertension, dyslipidemia,
      or diabetes, a thrombophilia workup is usually not considered in case of arterial
      thrombosis. The most accepted inherited hemostatic abnormalities associated with
      venous thromboembolism are factor V Leiden (FVL) and factor II (FII) G20210A
      mutations, as well as deficiencies in antithrombin (AT), protein C (PC), and
      protein S (PS). This review focuses on the link between these abnormalities and
      arterial thrombosis. Overall, the association between these genetic disorders and
      the three main arterial complications (myocardial infarction [MI], ischemic
      stroke [IS], and peripheral arterial disease [PAD]) is modest. Routine screening
      for these disorders is therefore not warranted in most cases of arterial
      complications. However, when such an arterial event occurs in a young person,
      inherited abnormalities of hemostasis seem to play a role, particularly when
      associated with smoking or oral contraceptive use. These abnormalities also seem
      to play a role in the risk of premature occlusion after revascularization
      procedures. Therefore thrombophilia tests may be informative in a very restricted
      population with arterial events. Anticoagulants rather than antiplatelet therapy
      may be preferable for these patients, although this remains to be proven.

PMID- 17433904
TI  - Quality assurance issues and interpretation of assays.
AB  - The consequences of an erroneous thrombophilia diagnosis may be serious if it is
      used to determine clinical management. Therefore careful selection, assessment,
      and control of laboratory tests for thrombophilia are essential. As for other
      coagulation tests, the pre-analytical phase must be carefully controlled with
      attention to the specific problems associated with each type of assay. The
      investigator must then recognize that for most laboratory tests of thrombophilia,
      there are a number of assay types available, often based on different principles
      of analysis. This creates the potential for different users to obtain varying
      results depending on the technique employed. Such problems can occur in assays of
      antithrombin activity, depending on whether the assay employs factor Xa, human
      thrombin, or bovine thrombin. In clot-based assays of protein C and protein S,
      there can be specificity problems related to interference by factor V Leiden
      (FVL), antiphospholipid antibodies, and other substances. Even genetic tests can
      give erroneous results and should not automatically be seen as absolute without
      supporting evidence and careful quality-control measures. Whatever technique is
      selected, it is mandatory to incorporate sufficient concurrent quality-control
      samples to validate the results of thrombophilia tests. These should include
      assessment of the parameter at normal and abnormal levels to give confidence in
      results across the measurement range that would normally be encountered in
      routine practice. This should be used in conjunction with regular participation
      in external quality assessment (EQA) (which has been linked to improved
      laboratory performance in thrombophilia testing). Larger EQA programs can provide
      information concerning the relative performance of analytical procedures,
      including the method principle, reagents, and instruments. Herein, we describe
      many of the methodologic effects in detail. We use specific examples to
      illustrate the general principle that, in performing laboratory testing for
      thrombophilia, one must always consider the performance characteristics and
      limitations of the assay in use.

PMID- 17433905
TI  - The essential role of genetic counseling in inherited thrombophilia.
AB  - The discovery of common genetic polymorphisms that predispose to venous
      thrombosis has led to the widespread availability of molecular testing for
      genetic thrombophilia traits. In terms of consent, genetic tests differ
      significantly from other types of laboratory test. We demonstrate the need for
      genetic counseling before and after genetic thrombophilia testing, but emphasize
      that such counseling need not be delivered by a specialist. We describe the
      potential advantages, limitations, and disadvantages of genetic testing for the
      common thrombophilic mutations that should be borne in mind when explaining
      testing to symptomatic individuals and asymptomatic relatives. In the vast
      majority of cases, genetic testing for thrombophilia is of limited value to the
      symptomatic patient, and provides minimal benefit over and above the family
      history when it comes to counseling at-risk family members.

PMID- 17433906
TI  - Why do we not all die of cancer at an early age?
AB  - Traditionally, surveillance against cancer was thought of as mainly
      immunological. With the exception of tumors with a clear viral involvement, such
      as immunoblastomas (Epstein-Barr virus, EBV), cervical, anogenital, and skin
      carcinomas (HPV), and Kaposi's sarcoma (HHV-8) where the immune system is
      confronted with virally encoded, nonself targets, tumors with no viral
      involvement provide poor targets. Attempts to influence them by immunological
      means are akin to the breaking of tolerance. Robust nonimmunological surveillance
      mechanisms include DNA repair-based checkpoint functions, and the triggering of
      growth arrest and/or apoptosis pathways by DNA damage or by illegitimate oncogene
      activation (intracellular surveillance). There is emerging evidence for
      epigenetic surveillance, reflected in the stringency of imprinting. A fourth
      mechanism, intercellular surveillance, or microenvironmental control, is rapidly
      gaining momentum. It can be mediated by contactual controls or by differentiation
      inducing signals. Somatic hybridization experiments have shown that
      tumorigenicity is usually suppressed in somatic hybrids between normal and
      malignant cells, as long as a fairly complete chromosome complement is
      maintained. Individual normal cell-derived chromosomes may have a similar
      suppressive effect. For example, genetic and molecular dissection of human 3p
      that shows frequent deletions in many human tumors has identified multiple tumor
      suppressor genes, which can inhibit both in vitro growth and in vivo
      tumorigenicity. In addition, five genes were found with an "asymmetric activity,"
      capable of suppressing tumorigenicity, without affecting in vitro growth. These
      genes, LTF, L1MD1, HYAL1, HYAL2, and VHL, are of particular interest because they
      may be involved in microenvironmental control.

PMID- 17433907
TI  - The early history of plasma cell tumors in mice, 1954-1976.
AB  - Plasma cell tumors (PCTs) in mice became available at an exciting period in
      immunology when many scientists and laboratories were occupied with how to
      explain the genetic basis of antibody diversity as well as antibody structure
      itself. An unlimited source of PCTs in an inbred strain of mice became a useful
      adjunct in these efforts. A PCT was a greatly expanded monoclone and a source of
      a single molecular species of immunoglobulin (Ig) molecule. The PCTs provided not
      only the components of the Ig-producing cell but also potentially functional
      secreted products. Many of the monoclonal Igs produced by PCTs in the mouse and
      others found in humans were found to have specific antigen-binding activities.
      These became the prototypes of monoclonal antibodies. This chapter describes the
      origins of PCTs in mice and attempts to recapture some of the ambience of the day
      albeit from personal recollection. The great discovery of the hybridoma
      technology by Cesar Milstein and Georges Kohler in 1975 began a new direction in
      immunology.

PMID- 17433908
TI  - Mouse mammary tumor biology: a short history.
AB  - For over a century, mouse mammary tumor biology and the associated Mouse mammary
      tumor virus (MMTV) have served as the foundation for experimental cancer
      research, in general, and, in particular, experimental breast cancer research.
      Spontaneous mouse mammary tumors were the basis for studies of the natural
      history of neoplasia, oncogenic viruses, host responses, endocrinology, and
      neoplastic progression. However, lacking formal proof of a human mammary tumor
      virus, the preeminence of the mouse model faded in the 1980s. Since the late
      1980s, genetically engineered mice (GEM) have proven extremely useful for
      studying breast cancer and have become the animal model for human breast cancer.
      Hundreds of mouse models of human breast cancer have been developed since the
      first demonstration, in 1984, that the mouse mammary gland could be molecularly
      targeted and used to test the oncogenicity of candidate human genes. Now, very
      few scientists can avoid using a mouse model to test the biology of their
      favorite gene. The GEM have attracted a new generation of molecular and cellular
      biologists eager to apply their skills to these surrogates of the human disease.
      Newcomers often enter the field without an appreciation of the origins of mouse
      mammary tumor biology and the basis for many of the prevailing concepts. Our
      purpose in writing this short history of mouse mammary tumor biology is to
      provide a historical perspective for the benefit of the newcomers. If Einstein
      was correct in that "we stand on the shoulders of giants," the neophytes should
      meet their giants.

PMID- 17433909
TI  - Ordered heterogeneity and its decline in cancer and aging.
AB  - Ordered heterogeneity was introduced as a basic feature of the living state in
      the mid-1950s. It was later expanded to "order in the large over heterogeneity in
      the small" as the first principle of a theory of organisms. Several examples of
      ordered heterogeneity were given at the time to illustrate the principle, but
      many more have become apparent since then to confirm its generality. They include
      minimum size requirements for progressive embryological development, the errant
      behavior of cells liberated from tissue architecture, their sorting out to
      reconstitute tissues on reaggregation, and contact regulation of cell
      proliferation. There is increasing heterogeneity of cell growth with age, and
      marked heterogeneity of many characters among cells of solid epithelial tumors.
      Normal growth behavior is reintroduced in solitary, carcinogen-initiated
      epidermal cells by contact with an excess of normal epidermal cells. Contact
      normalization also occurs when solitary hepatocarcinoma cells are transplanted
      into the parenchyma of normal liver of young, but not of old, animals. The role
      of the plasma membrane and adhesion molecules in ordering heterogeneity is
      evaluated. Organizing the results in a conceptual structure helps to understand
      classical observations of tumor biology such as the lifetime quiescence of
      carcinogen-initiated epidermal cells and the marked increase of cancer incidence
      with age. The principle of order above heterogeneity thus provides a unifying
      framework for a variety of seemingly unrelated processes in normal and neoplastic
      development. Whereas contact between cells is required for these processes to
      occur, gap junctional communication is not required.

PMID- 17433910
TI  - Reversal of tumor resistance to apoptotic stimuli by alteration of membrane
      fluidity: therapeutic implications.
AB  - In recent years, significant development and improvement have been observed in
      the treatment of cancer; however, relapses and recurrences occur frequently and
      there have not been any current therapies to treat such cancers. Cancers
      resistant to conventional therapies develop several mechanisms to escape death
      inducing stimuli. A poorly understood mechanism is the involvement of the cancer
      cell plasma membrane composition and architecture and their involvement in
      regulating drug-inducing stimuli leading to cell death. Although the basic
      structure of the biological membrane was established 80 years ago, study of the
      physical properties of lipid bilayers still provides significant information
      regarding membrane organization and dynamics. Membrane fluidity is probably the
      most important physicochemical property of cell membranes. Alterations of
      membrane fluidity can seriously affect functional properties of the cell and
      induction of apoptotic pathways resulting in cell death. The role of membrane
      fluidity in the apoptotic process is clearly exemplified as it is seriously
      disrupted as a result of cell injury. The molecular signaling pathways leading to
      apoptosis are currently promising areas of research investigation and lead to
      unravel the underlying molecular mechanisms of tumor cells resistance to
      apoptotic stimuli and hence the development of new effective therapeutic agents.
      Recent findings indicate that most anticancer agents induce apoptosis, directly
      or indirectly, through alterations of tumor cell membrane fluidity. The present
      chapter summarizes the relationship between alterations of tumor cell membrane
      fluidity and tumor cell response to apoptotic-inducing stimuli. Several potential
      therapeutic applications directed at tumor cell membrane fluidity are proposed.

PMID- 17433911
TI  - Mutant transcription factors and tyrosine kinases as therapeutic targets for
      leukemias: from acute promyelocytic leukemia to chronic myeloid leukemia and
      beyond.
AB  - Mutations in transcription factors (TFs) and protein tyrosine kinases (PTKs),
      which result in inhibition of differentiation/apoptosis or enhanced
      proliferative/survival advantage of hematopoietic stem/progenitor cells, are two
      classes of the most frequently detected genetic abnormalities in leukemias. The
      critical roles for mutant TFs and/or PTKs to play in leukemogenesis, and the
      absence of mutant TFs/PTKs in normal hematopoietic cells, suggest that the two
      types of aberrant molecules may serve as ideal therapeutic targets. The great
      success of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) in treating
      acute promyelocytic leukemia through modulation of the causative PML-RARalpha
      oncoprotein represents the first two paradigms of mutant TFs-targeting
      therapeutic strategies for leukemia. More recently, tyrosine kinase inhibitor STI
      571/Imatinib mesylate/Gleevec in the treatment of Breakpoint Cluster Region
      Abelson (BCR-ABL) positive leukemia elicits paradigm of mutant PTKs as ideal
      antileukemia targets. Thus to further improve clinical outcome of leukemia
      patients, elucidation of pathogenesis of leukemia, screening for oncoprotein
      targeting small molecules, as well as rationally designed combination of drugs
      with potential synergy are of importance.

PMID- 17433912
TI  - The effect of cell-matrix interactions and aging on the malignant process.
AB  - The malignant process, transformation of normal cells, proliferation, and
      metastasis formation, was considered as if originating from one single cell.
      Although the intrinsic mechanisms of transformation from the normal to the
      malignant state were both confirmed, an increasing body of evidence points to the
      surrounding matrix and cell-matrix interactions as major players in this process.
      Some of the most important arguments in favor of this contention are cited and
      commented in this chapter. Another important question concerns the relationship
      between the aging process and malignant transformation. A few decades ago, the
      frequency of clinically manifest tumors of several organs and tissues appeared to
      increase with age. As, however, average life expectancy increased rapidly over
      the last decades, clinical frequency of malignant tumors did not follow this
      tendency. It was argued that late in life the malignant process appears to
      decline. This justly inspired several teams to study the relationship between
      cellular senescence and malignant transformation. This is now an actively growing
      field which deserves special attention. Some of the pertinent experimental and
      theoretical arguments in favor of an antioncogene-mediated switch between these
      two processes are also reviewed with the caveat that this important and new
      subject of basic and clinical research on the malignant process is just at its
      beginning. It will certainly take an increasing importance during the coming
      years and decades with the hope to contribute to answer one of the most burning
      questions concerning the aging process: will life expectancy continue to increase
      linearly as predicted by some gerontologists, or will life expectancy level off
      or even decline as predicted by other epidemiologists. The relationship between
      cellular senescence and malignant transformation will play in this respect an
      important role.

PMID- 17433914
TI  - Epilepsy in the elderly: scope of the problem.
AB  - The knowledge base for treating elderly persons with epilepsy is limited. There
      are few known knowns, many known unknowns, and probably many unknown knowns, that
      is, the things we know that "ain't so." We know that the incidence and prevalence
      of epilepsy is higher in the elderly than any other age group, that the elderly
      are not a homogeneous group, that epilepsy is much more common in the nursing
      home population than in the community-dwelling elderly, and that antiepileptic
      drug (AED) use varies greatly among countries, but that in all, the older AEDs
      (phenytoin, phenobarbital, and carbamazepine) are the most commonly used. We also
      know that drugs that require hepatic metabolism for elimination are subject to
      pharmacokinetic changes with age and may be problematic because of drug-drug
      interactions. There are many known unknowns in both the basic science of brain
      aging and the susceptibility to epilepsy, and many clinical issues remain
      unresolved. Some unknown knowns (i.e., misconceptions) are that the elderly need
      levels of AEDs similar to those for younger adults and that AED levels do not
      fluctuate widely. This book is designed to help the reader understand the issues
      and, hopefully, to stimulate research to provide answers for the known unknowns.

PMID- 17433915
TI  - Animal models in gerontology research.
AB  - Animal models have paved the way for the vast majority of advances in biomedical
      research. Studies on aged animals are essential for understanding the processes
      inherent in normal aging and the progression of age-related diseases. Animal
      models are used to identify physiological changes with age, to identify the
      genetic basis of normal aging and age-associated disease and degeneration, and to
      test potential therapeutic interventions. This chapter will focus on rodent
      models and will summarize important considerations for the use of animals in
      aging research in general and in modeling geriatric epilepsy.

PMID- 17433916
TI  - Animal models of geriatric epilepsy.
AB  - Geriatric epilepsy is a significant clinical problem that has not been studied
      adequately in animal models. This chapter will review the available literature
      with particular attention to models that have demonstrated how acute seizures and
      epilepsy in aged animals differ from those of younger animals. Studies include
      several strains of mice [e.g., El, DBA, senescence-accelerated mouse (SAM),
      Cacnb4 knockout] as well as acute seizure models in common strains of aged mice.
      Aged rats (including Fischer 344, Wistar, and Sprague-Dawley) have been used in
      acute seizure, lesion, and epilepsy models. This area of research remains largely
      unexplored and therefore provides numerous opportunities for new investigations.

PMID- 17433917
TI  - Life and death of neurons in the aging cerebral cortex.
AB  - The transition from age-associated memory impairment (AAMI) to the dramatic loss
      of cognitive abilities accompanying Alzheimer's disease (AD) requires progressive
      development of neocortical pathology that results in neuron death. The selective
      vulnerability of this neuron death is reflected in the characteristics of
      cortical pyramidal neurons that are prone to form neurofibrillary tangles. Loss
      of the neurons that form long corticocortical projections in the association
      neocortex emerges as the pathological outcome most directly related to the
      dementia observed in AD. AAMI likely involves alterations of neuronal spines and
      synapses without neuron death. Interestingly, the same circuits that are
      vulnerable to degeneration in AD are vulnerable to synaptic alterations short of
      neuron death. These synaptic alterations likely impact cognitive function in
      normal aging in a manner consistent with the more modest cognitive decline
      typically seen in aging. Estrogen levels affect spine density on pyramidal
      neurons in the prefrontal cortex; these neurons may provide many of the same
      circuits implicated in AAMI. This association demonstrates an important interface
      between reproductive and neural senescence and suggests that the synaptic
      alterations prevalent in normal aging may be responsive to therapy.

PMID- 17433918
TI  - An in vitro model of stroke-induced epilepsy: elucidation of the roles of
      glutamate and calcium in the induction and maintenance of stroke-induced
      epileptogenesis.
AB  - Stroke is a major risk factor for developing acquired epilepsy (AE). Although the
      underlying mechanisms of ischemia-induced epileptogenesis are not well
      understood, glutamate has been found to be associated with both epileptogenesis
      and ischemia-induced injury in several research models. This chapter discusses
      the development of an in vitro model of epileptogenesis induced by glutamate
      injury in hippocampal neurons, as found in a clinical stroke, and the
      implementation of this model of stroke-induced AE to evaluate calcium's role in
      the induction and maintenance of epileptogenesis. To monitor the acute effects of
      glutamate on neurons and chronic alterations in neuronal excitability up to 8
      days after glutamate exposure, whole-cell current-clamp electrophysiology was
      employed. Various durations and concentrations of glutamate were applied to
      primary hippocampal cultures. A single 30-min, 5-microM glutamate exposure
      produced a subset of neurons that died or had a stroke-like injury, and a larger
      population of injured neurons that survived. Neurons that survived the injury
      manifested spontaneous, recurrent, epileptiform discharges (SREDs) in neural
      networks characterized by paroxysmal depolarizing shifts (PDSs) and high
      frequency spike firing that persisted for the life of the culture. The neuronal
      injury produced in this model was evaluated by determining the magnitude of the
      prolonged, reversible membrane depolarization, loss of synaptic activity, and
      neuronal swelling. The permanent epileptiform phenotype expressed as SREDs that
      resulted from glutamate injury was found to be dependent on the presence of
      extracellular calcium. The "epileptic" neurons manifested elevated intracellular
      calcium levels when compared to control neurons, independent of neuronal activity
      and seizure discharge, demonstrating that alterations in calcium homeostatic
      mechanisms occur in association with stroke-induced epilepsy. Findings from this
      investigation present the first in vitro model of glutamate injury-induced
      epileptogenesis that may help elucidate some of the mechanisms that underlie
      stroke-induced epilepsy.

PMID- 17433919
TI  - Mechanisms of action of antiepileptic drugs.
AB  - The management of seizures in the patient with epilepsy relies heavily on
      antiepileptic drug (AED) therapy. Fortunately, for a large percentage of
      patients, AEDs provide excellent seizure control at doses that do not adversely
      affect normal function. At the molecular level, the majority of AEDs are thought
      to modify excitatory and inhibitory neurotransmission through effects on voltage
      gated ion channels (e.g., sodium and calcium) and gamma-aminobutyric acid
      (GABA)(A) receptors, respectively. In addition to these effects, two of the
      "second-generation" AEDs have been found to limit glutamate-mediated excitatory
      neurotransmission (i.e., felbamate and topiramate). Not surprisingly, those AEDs
      with broad spectrum clinical activity are often found to exert an action at more
      than one molecular target. Emerging evidence suggests that receptor and voltage
      gated subunits are modified by chronic seizures. Thus, attempts to understand the
      relationship between target and effect continue to provide important information
      about the neuropathology of the epileptic network and to facilitate the
      development of novel therapies for the treatment of refractory epilepsy.

PMID- 17433920
TI  - Epidemiology and outcomes of status epilepticus in the elderly.
AB  - Status epilepticus (SE) is a serious condition of prolonged or repetitive
      seizures. The annual incidence (86/100,000) of SE in the elderly who are aged 60
      and greater is almost twice that of the general population and is even higher in
      those who are 70 years and older. Either acute or remote symptomatic stroke
      causes approximately 60% of SE seen in the elderly. SE is associated with a high
      mortality in the elderly (38%), with a rate approaching 50% in patients older
      than 80 years of age. Etiology is a strong determinant of mortality in the
      elderly: mortality approaches 100% in patients with anoxia and 30% in patients
      with either metabolic disorders, hemorrhages, tumors, or systemic infections.
      Mortality is almost three times higher in SE associated with acute ischemic
      stroke than in stroke alone, indicating synergistic effects. Duration of SE is
      also a factor in mortality. Treatment should be initiated for any convulsive
      seizure that lasts at least 10 min or is repetitive. An electroencephalogram
      (EEG) should be promptly obtained so that a diagnosis can be made without delay.
      Because older patients have a greater likelihood of nondiagnostic findings on
      routine EEGs, prolonged EEG recordings and inpatient video-EEG monitoring
      significantly increase the rate of establishing a definitive diagnosis.
      Nonconvulsive status epilepticus in the elderly is especially difficult to
      diagnose and should be evaluated with an EEG. Treatment of SE is complicated by
      altered pharmacokinetics in the elderly. Initial treatments, usually the
      administration of an intravenous benzodiazepine, have overall success rates of
      55% for overt convulsive SE and 14.9% for subtle SE. For refractory SE, little is
      gained by using additional standard drugs, and general anesthesia with continuous
      EEG monitoring is recommended.

PMID- 17433921
TI  - Diagnosing epilepsy in the elderly.
AB  - Elderly individuals represent the fastest-growing segment of the US population.
      Seizures are common among elderly persons, and the etiology, clinical
      presentation, and prognosis of seizure disorders can often differ between elderly
      patients and younger individuals. However, published information regarding the
      diagnosis and management of epilepsy in elderly patients is scarce. Because a
      number of conditions that are common in elderly patients may resemble epilepsy,
      diagnosis can be challenging. Cardiovascular conditions, migraines, drug effects,
      infections, metabolic disturbances, sleep disorders, and psychiatric disorders
      are all associated with signs and symptoms that may often mimic epilepsy. New
      paradigms must be put into practice to establish an accurate diagnosis in the
      elderly patient; besides an initial evaluation, the patient history and an
      electroencephalogram should be obtained. Proper diagnosis is essential for proper
      treatment in the elderly patient.

PMID- 17433922
TI  - Pharmacoepidemiology in community-dwelling elderly taking antiepileptic drugs.
AB  - This study used the national inpatient, outpatient, and pharmacy databases from
      the US Veterans Health Administration to examine prescribing patterns for older
      patients with epilepsy and to determine the factors associated with receiving
      recommended antiepileptic drugs (AEDs) such as lamotrigine, gabapentin, or
      carbamazepine. Among patients with epilepsy, the AED monotherapy most prescribed
      was phenytoin (70%), followed by phenobarbital (17%). While the rate of phenytoin
      use was similar for both previously and newly diagnosed patients with epilepsy,
      phenobarbital was less commonly used in newly diagnosed patients. Multivariable
      analyses suggested that receiving outpatient neurological care was the strongest
      predictor of receipt of recommended AED regimens in newly diagnosed elderly
      patients with epilepsy. These data suggest that the challenge remains to narrow
      the gap between expert recommendations and actual practice if patients with
      epilepsy are to fully benefit from the tremendous progress that has been made in
      the pharmacological management of this disease.

PMID- 17433923
TI  - Use of antiepileptic medications in nursing homes.
AB  - The University of Minnesota Epilepsy Research and Education Program published two
      studies evaluating the use of antiepileptic drugs (AEDs) among nursing home (NH)
      elderly. The studies used a large, nongovernmental data set for studying this
      population. This chapter is a summary of those two studies. In the first study, a
      1-day point prevalence study, 10.5% of the NH residents had one or more AED
      orders, a prevalence 10 times greater than that found in the community. In a
      multivariate analysis of factors associated with AED treatment, seizure
      indication was the most important factor, and age was inversely related to AED
      use. Phenytoin was the most commonly used AED, followed by carbamazepine,
      phenobarbital, and valproic acid. The most frequently used combination was
      phenytoin and phenobarbital. In the second study, evaluating NH admission data,
      8% of newly admitted residents were already receiving one or more AEDs when they
      entered the NH. Factors associated with AED use in this group included
      epilepsy/seizure disorder, age, cognitive performance, and manic depression
      (bipolar disease). Among residents recently admitted who were not using an AED at
      entry, 3% were initiated on an AED within 3 months of admission. Among the
      factors associated with the initiation of AEDs during this period, the strongest
      association was with epilepsy/seizure disorder. Manic depression (bipolar
      disease) was also significantly associated with initiation of an AED after
      admission. In this group, there was an inverse relationship between age and
      initiation of an AED.

PMID- 17433924
TI  - Age-related changes in pharmacokinetics: predictability and assessment methods.
AB  - Although there have been relatively few studies of the pharmacokinetics of
      antiepileptic drugs (AEDs) in old age, available evidence indicates that the
      clearance of most old and new generation AEDs is reduced on average by about 20
      40% in elderly patients compared with nonelderly adults. Depending on the
      pharmacokinetic characteristics of the drug, the reduction in clearance can be
      ascribed to a physiological reduction in rate of drug metabolism, to a decrease
      in renal excretion rate, or to both. Studies have consistently demonstrated that
      interindividual pharmacokinetic variability in old age is particularly prominent,
      due not only to the influence of aging-related physiological changes, but also to
      the impact of comorbidities and drug-drug interactions. For extensively
      metabolized drugs, there are no reliable tools to predict with a high degree of
      accuracy the pharmacokinetic behavior of an AED in an individual patient. With
      renally eliminated drugs, determination of creatinine clearance may provide a
      useful clue in predicting individual changes in drug clearance and the consequent
      need for dosage adjustment. In the therapeutic setting, measurement of serum AED
      concentrations can be valuable in individualizing dosage in an elderly person,
      even though it should be remembered that in the case of drugs that are highly
      bound to plasma proteins the total serum concentration may underestimate the
      level of unbound, pharmacologically active drug. Because aging is also associated
      with important pharmacodynamic changes that may alter the relationship between
      serum drug concentration and pharmacological effects, pharmacokinetic
      measurements alone are not a substitute for the need to monitor clinical response
      carefully and to adjust dosage accordingly.

PMID- 17433925
TI  - Factors affecting antiepileptic drug pharmacokinetics in community-dwelling
      elderly.
AB  - Because aging is associated with changes in physiological processes, it is widely
      believed that antiepileptic drug pharmacodynamics and pharmacokinetics in elderly
      patients differ from those in younger adults. In order to better characterize
      these differences, this chapter reports on preliminary results from an
      investigation of the effect of age on steady-state phenytoin (PHT) and
      carbamazepine (CBZ) pharmacokinetics. Parenteral formulations of stable-labeled
      PHT, fosphenytoin (FOS), and CBZ were administered to elderly (> or =65 years of
      age) and adult (18-64 years of age) patients on maintenance regimens of PHT or
      CBZ; a labeled 100-mg dose was infused over 10 min, then the remainder of the
      patient's AED dose was administered as unlabeled drug. Blood samples were
      collected just before administration of the labeled drug and for up to 192 h
      afterward. Samples were then assayed for the concentrations of labeled and
      unlabeled drug. Preliminary results from 60 patients on PHT therapy (41 elderly,
      mean age 76 years; 19 younger adults, mean age 41 years) indicate that PHT
      bioavailability did not differ between the two age groups; however, absorption
      and elimination half-lives were more variable in the elderly patients. The
      elimination half-life for the entire patient population was approximately twofold
      longer than the value reported in the product labeling (40-50 h vs 22 h).
      Preliminary results from 67 patients on CBZ therapy (14 elderly, mean age 70
      years; 53 younger adults, mean age 41 years) showed no apparent difference
      between elderly and adult patients in any parameter; however, the mean CBZ
      elimination half-life for the combined groups (21 h) was longer than previous
      estimates. These results indicate that the effect of age on CBZ and PHT
      absorption may result in greater variability in plasma concentrations in elderly
      patients, whereas the effect on half-life is modest.

PMID- 17433926
TI  - Pharmacokinetics of antiepileptic drugs in elderly nursing home residents.
AB  - With approximately 10% of elderly nursing home residents taking antiepileptic
      drugs (AEDs), it is critical to understand the pharmacokinetics, dosing, and
      possible adverse reactions of these AEDs. In this chapter, five AEDs commonly
      prescribed to nursing home residents will be discussed. Phenytoin (PHT), the most
      commonly used AED in this population, is extensively metabolized by the
      cytochrome P450 enzyme system, is highly protein bound, and interacts with many
      concomitant medications. Up to 45% of nursing home residents who receive PHT have
      concentrations below the range (subtherapeutic) used in adults (<65 years), while
      approximately 10% of residents have concentrations that are potentially toxic
      (>20 microg/ml). In addition, serum PHT concentrations can vary greatly within an
      individual resident and may be subtherapeutic one day and potentially toxic the
      next. Valproic acid is taken by approximately 9-17% of nursing home residents who
      are administered AEDs, with over half using it for nonseizure indications. Doses
      are approximately 16 mg/kg/day in elderly nursing home residents, but doses and
      serum concentrations are lower in the oldest age group (> or =85 years). A
      majority of residents are maintained at serum concentrations considered
      subtherapeutic for epilepsy, whereas relatively few (approximately 3%) are
      maintained at toxic levels. The average (+/-SD) carbamazepine (CBZ) dose is 8.8
      +/- 4.7 mg/kg/day, yielding a mean serum concentration of 6.3 +/- 2.2 mg/liter.
      Subtherapeutic concentrations are found in up to 20% of serum measurements, while
      2.5% of serum measurements are in the toxic range. CBZ is highly bound to serum
      albumin and alpha1-acid glycoprotein and is metabolized to carbamazepine-10,11
      epoxide, an active metabolite thought to be responsible for some side effects.
      Phenobarbital (PB) is frequently combined with PHT. This combination can cause
      devastating side effects because both PB and PHT can produce cognitive side
      effects. Gabapentin is one of the newer AEDs frequently administered to nursing
      home residents. Its lack of both hepatic metabolism and protein binding
      potentially makes it a safer drug in this population.

PMID- 17433927
TI  - The impact of epilepsy on older veterans.
AB  - Despite the fact that old age is the time with the highest incidence of epilepsy,
      little is known specifically about the impact of epilepsy on the daily lives of
      the elderly. Previous studies have explored the impact of epilepsy on health
      status in a general population, but typically have not included enough older
      individuals to adequately describe this population. The study on which this
      chapter is based used a general survey instrument to begin exploration of this
      issue in a population of older veterans with epilepsy. Older patients (> or =65
      years of age) were identified who had both International Classification of
      Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), codes indicating
      epilepsy and prescriptions of antiepileptic drugs in national Veterans Affairs
      (VA) administrative and pharmacy databases during fiscal year 1999. Using these
      databases, patients were further identified as newly or previously diagnosed.
      Diagnostic data were then linked with data from the 1999 Large Health Survey of
      Veteran Enrollees, using encrypted identifiers, and the impact of epilepsy on
      patients of different ages was assessed using individual scales and component
      summaries of the Veterans SF-36. Results showed that older individuals with
      epilepsy had lower scores on measures of both physical and mental health than did
      their counterparts with no epilepsy. Further, scores associated with mental
      health functioning were significantly lower for those with newly diagnosed
      epilepsy than for those with chronic epilepsy, but differences associated with
      scores on physical functioning were not significant. Thus, while previous studies
      suggest that the effects of chronic neurological disorders such as epilepsy are
      most obvious on measures of mental health, these data suggest that older patients
      experience difficulties in both physical and mental health.

PMID- 17433928
TI  - Risk and predictability of drug interactions in the elderly.
AB  - The issue of drug-drug interactions is particularly relevant for geriatric
      patients with epilepsy because they are often treated with multiple medications
      for concurrent diseases such as cardiovascular disease and psychiatric disorders
      (e.g., dementia and depression). The antidepressants with the least potential for
      altering antiepileptic drug (AED) metabolism are citalopram, escitalopram,
      venlafaxine, duloxetine, and mirtazapine. The use of established AEDs with enzyme
      inducing properties, such as carbamazepine, phenytoin, and phenobarbital, may be
      associated with reductions in the levels of drugs such as donepezil, galantamine,
      and particularly warfarin. Carbamazepine, phenytoin, and phenobarbital have been
      reported to decrease prothrombin time in patients taking oral anticoagulants,
      although with phenytoin, an increase in prothrombin time has also been reported.
      Drugs associated with increased risk of bleeding in patients taking oral
      anticoagulants include selective serotonin reuptake inhibitors (especially
      fluoxetine), gemfibrozil, fluvastatin, and lovastatin. Other drugs affected by
      enzyme inducers include cytochrome P450 3A4 substrates, such as calcium channel
      blockers (e.g., nimodipine, nilvadipine, nisoldipine, and felodipine) and the 3
      hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors atorvastatin,
      lovastatin, and simvastatin. Although there have been no reports of AEDs altering
      ticlopidine metabolism, ticlopidine coadministration can result in carbamazepine
      and phenytoin toxicity. Also, there is a significant risk of elevated levels of
      carbamazepine when diltiazem and verapamil are administered. In addition, there
      are case reports of phenytoin toxicity when administered with diltiazem. Drugs
      with a lower potential for metabolic drug interactions include (1) cholinesterase
      inhibitors (although the theoretical possibility of a reduction in donepezil and
      galantamine levels by enzyme-inducing AEDs should be considered) and the N-methyl
      D-aspartate receptor antagonist memantine and (2) antihypertensives such as
      angiotensin-converting enzyme inhibitors, angiotensin receptor blockers,
      hydrophilic beta-blockers, and thiazide diuretics. There is a moderate risk that
      enzyme-inducing AEDs will decrease levels of lipophilic beta-blockers. Newer AEDs
      have a lower potential for drug interactions. In particular, levetiracetam and
      gabapentin have not been reported to alter enzyme activity. In summary, there is
      a significant potential for drug interactions between AEDs and drugs commonly
      prescribed in geriatric patients with epilepsy.

PMID- 17433929
TI  - Outcomes in elderly patients with newly diagnosed and treated epilepsy.
AB  - Epilepsy develops most commonly in the elderly. Seizures can severely affect a
      senior citizen's quality of life, and despite a growing elderly population with
      epilepsy, there is a paucity of good clinical data in this age group. To address
      some of the issues encountered by elderly patients with epilepsy, prospective
      information from elderly patients attending the Epilepsy Unit at the Western
      Infirmary in Glasgow, Scotland, was analyzed. Ninety patients, aged 65-93 years,
      were diagnosed with epilepsy and started on antiepileptic drug (AED) treatment.
      Neuroimaging was performed in 84 patients (93%), with 69 evaluated via
      computerized tomography and 15 via magnetic resonance imaging; abnormalities were
      found in 45 patients (54%). Sixty-eight patients underwent interictal
      electroencephalography, which revealed epileptiform discharges in 18 patients
      (26%). Fifty-eight of 90 patients (64%) became seizure free for at least 12
      months on modest doses of the first prescribed AED. Seizures remained
      uncontrolled in 21 patients (23%), and the first AED was withdrawn in 11 patients
      (12%) because of adverse events. Following pharmacological manipulation, a total
      of 76 patients (84%) achieved seizure freedom. Patients starting treatment > or
      =2 years after their first seizure were less likely to achieve seizure control
      than patients who initiated treatment earlier. Newly diagnosed elderly patients
      were more likely to remain seizure free on AED treatment than newly diagnosed
      younger populations (p < 0.001). The majority of patients evaluated had partial
      onset seizures, and underlying cerebral atrophy and infarcts were common.
      Treating an older person with initial AED therapy can be complicated; taking
      adequate time and communicating clearly are paramount. Although most of the
      patients evaluated had a positive outcome, all AEDs have some disadvantages in
      this population. Choice of drug may depend on comorbidity and comedication, among
      other factors. Initial dosing should be low with a slow titration schedule. A
      holistic approach to care helps optimize the outcome for elderly people with
      epilepsy.

PMID- 17433930
TI  - Recruitment and retention in clinical trials of the elderly.
AB  - The recruitment and retention of elderly patients in clinical trials provide many
      challenges. Factors affecting recruitment, retention, and cost of recruitment are
      discussed in this chapter. Various methods are described that were used in
      recruiting and retaining elderly patients in a Veterans Affairs (VA)
      Administration clinical trial that compared two newer antiepileptic drugs (AEDs),
      gabapentin and lamotrigine, to the established standard AED, carbamazepine.
      Various strategies were utilized in the VA study to improve recruitment, and each
      strategy's overall effectiveness was monitored. Modification of the patient
      inclusion criteria, by lowering the age of eligibility from 65 to 60 years, added
      approximately 100 patients to the study. Replacing five trial sites that had poor
      recruiting records, extending the patient recruitment period by 3 months, and
      conducting site visits also improved patient recruitment rates, such that 82.4%
      of target enrollment (720 patients) was achieved. The main reasons that screened
      patients were excluded from the study included: lack of seizures during the prior
      3 months, unstable medical condition, adequate treatment with an AED,
      satisfaction with current treatment, and the inability to give informed consent.
      Retaining patients for 1 year was the primary outcome measure of this trial, with
      46.8% of patients completing the year. The most common reasons for early
      termination were study drug-related adverse events (43.0%) and lack of seizure
      control (10.8%). Comorbidities and polypharmacy occurred more frequently in the
      elderly, and both had a negative influence on recruitment and retention.

PMID- 17433931
TI  - Treatment of convulsive status epilepticus.
AB  - Status epilepticus (SE) is a medical and neurological emergency requiring prompt
      and aggressive treatment, particularly for elderly individuals in whom comorbid
      conditions may increase the severity of consequences in SE. Generalized
      convulsive status epilepticus (GCSE) is the most common and life-threatening type
      of SE. It may be overt or subtle in its presentation. Most cases are overt, but
      as the duration of GCSE increases, its presentation may become more subtle.
      Progressive electroencephalographic changes also occur during GCSE. A predictable
      sequence of five electroencephalographic patterns has been identified: (1)
      discrete seizures with interictal slowing, (2) merging seizures with waxing and
      waning ictal discharges, (3) continuous ictal sharp or spike-wave discharges, (4)
      continuous ictal discharges with episodes of generalized flattening, and (5)
      periodic epileptiform discharges superimposed on a relatively flat background.
      Several factors affect the prognosis of GCSE, including etiology, age, seizure
      type, gender, and duration. GCSE may lead to systemic complications and neuronal
      damage and is often fatal if untreated or inadequately treated. Treatment of GCSE
      should begin with basic life support measures and monitoring. Ideally,
      pharmacological treatment should be easy to administer and fast acting. Analysis
      of data on elderly patients with overt GCSE from a Veterans Affairs cooperative
      study revealed that success rates of first-line treatment were 71.4% for
      phenobarbital, 63.0% for lorazepam, 53.3% for diazepam followed by phenytoin, and
      41.5% for phenytoin alone. In elderly patients with subtle GCSE, success rates
      for first-line treatment were 30.8% for phenobarbital, 14.3% for lorazepam, 11.8%
      for phenytoin, and 5.6% for diazepam followed by phenytoin. Because each drug has
      advantages and disadvantages, the choice of which agent to use as first-line
      treatment depends on individual patient characteristics.

PMID- 17433932
TI  - Treatment of nonconvulsive status epilepticus.
AB  - Nonconvulsive status epilepticus (NCSE) is relatively common; it comprises at
      least one third of all cases of status epilepticus. NCSE may be an even more
      common, yet more elusive, condition in the elderly population. NCSE can be
      divided into complex partial status epilepticus (CPSE), NCSE in coma, and typical
      absence status epilepticus (TAS). The clinical manifestations may be subtle, and
      thus the diagnosis of these conditions is critically dependent on
      electroencephalography (EEG). When EEG demonstrates typical ictal patterns, the
      diagnosis is usually straightforward. However, in many circumstances the EEG
      pattern has to be differentiated from other encephalopathic patterns, and this
      differentiation can prove troublesome; clinical and electrographic response to
      treatment can prove helpful in these situations. The prognosis for NCSE in the
      elderly is generally poor due to the underlying etiology rather than the
      persistence of electrographic discharges. Whether the neuronal damage that occurs
      in convulsive status epilepticus and in animal models of limbic status
      epilepticus also occurs in NCSE in humans is still a matter of debate.
      Intravenous treatment is not benign, especially in the elderly, who may be at
      greater risk of systemic complications from hypotensive and sedative agents.
      Therefore, a more conservative approach to the treatment of NCSE in the elderly
      is warranted. Oral benzodiazepines should be used for the treatment of TAS and
      CPSE in noncomatose patients with a prior history of epilepsy, and in some
      circumstances, intravenous medication may be necessary. Generally, anesthetic
      coma should not be advised in either of these conditions. A more aggressive
      approach may be required with NCSE in coma, in the hope of improving a very poor
      prognosis. Treatment regimens will remain largely speculative until there are
      more relevant animal models and controlled trials of conservative versus
      aggressive treatment.

PMID- 17433933
TI  - Antiepileptic drug formulation and treatment in the elderly: biopharmaceutical
      considerations.
AB  - The pharmacokinetics of antiepileptic drugs (AEDs) determine their effectiveness
      in the treatment of patients with epilepsy. Given the likelihood of comorbid
      medical conditions that require polytherapy, as well as the normal physiological
      changes associated with aging, an understanding of AED pharmacokinetics and
      pharmacodynamics in the elderly patient is critical. There is a relative sparsity
      of data regarding changes in the oral absorption patterns of AEDs that may
      accompany aging. Therefore, the objective of this chapter is to discuss
      fundamental principles related to oral drug absorption, and to discuss their
      potential impact on AED treatment in the older patient. Although most drugs are
      absorbed via the diffusion process, active transport also plays a role in
      absorption. While the gastrointestinal tract shows remarkable resilience during
      aging, physiological changes that influence oral and esophageal function, gastric
      pH, gastric emptying rates, and intestinal transit times do occur. Oral
      administration of AEDs may be affected by changes associated with aging,
      including altered oral protective reflexes, xerostomia, thickening of the
      esophageal smooth muscle layer, reduced contraction velocity and duration,
      altered esophageal emptying rates, and enteric plexus neuron reduction. Gastric
      acid secretion is similar between older and younger patients, but older patients
      require more time to return to baseline gastric pH values and have prolonged
      gastric emptying rates compared to younger patients. Elderly patients may
      similarly have reduced numbers of myenteric neurons, decreased postprandial
      contractions, reduced frequency of migrating motor complex, and diminished rectal
      compliance as well as reduced sphincter tones. All of these effects observed in
      the aging patient, in turn, produce numerous opportunities for changes in AED
      absorption, particularly for those agents demonstrating poor water solubility or
      variable absorption patterns.

PMID- 17433934
TI  - Infection control certification: a global priority.

PMID- 17433935
TI  - Should states rely on administrative data alone when publicly reporting health
      care-associated infections?

PMID- 17433936
TI  - Comparisons of health care-associated infections identification using two
      mechanisms for public reporting.
AB  - BACKGROUND: Many states have or are in process of legislating hospitals to report
      health care-associated infections (HAI). The purpose of this article is to
      compare two methods currently in use by different states: 1) selected infections
      due to medical care Patient Safety Indicator (PSI-7); and 2) Centers for Disease
      and Prevention Control (CDC) protocols for central line-associated bloodstream
      infections (CLA-BSI). METHODS: Data came from a multihospital study. Site
      coordinators provided lists of elderly Medicare patients admitted in an enrolled
      intensive care unit in 2002 cross referenced with patient specific data on CLA
      BSI following CDC protocols. PSI-7 was identified using Medicare data and the
      Agency for Healthcare Research and Quality PSI software version 2.1. RESULTS: The
      full sample comprised records from 14,637 patients from 41 intensive care units
      in 24 hospitals. Patients were excluded if they did not meet the PSI-7
      denominator criteria. In a sample of 9,948 patients, both methods identified
      infections in 89 (0.89%) patients. The methods had little concordance with only 8
      patients identified using both methods. CONCLUSIONS: Inconsistencies that we
      identified in this study are concerning given the fact that reports of HAI
      generated by different methods vary widely. Mandatory reporting mechanisms should
      be standardized and their accuracy confirmed.

PMID- 17433937
TI  - The Certification Board of Infection Control and Epidemiology white paper: the
      value of certification for infection control professionals.
AB  - In its Vision 2012: A Strategic Plan, the Association for Professionals in
      Infection Control and Epidemiology, Inc. (APIC) states that APIC will be
      recognized as the leader in infection prevention and control. However, if the
      APIC Strategic Plan is to be advanced by its members, infection control
      professionals must choose a leadership role by becoming certified, validating
      their competency and setting a standard of excellence. Certification by the
      Certification Board of Infection Control and Epidemiology, Inc. (CBIC) validates
      an infection control professional's competence to the public, the profession,
      employers, and regulators. The White Paper presented here by the CBIC provides a
      rationale for certification and recertification in infection prevention and
      control practice.

PMID- 17433938
TI  - A point prevalence survey of health care-associated infections in pediatric
      populations in major Canadian acute care hospitals.
AB  - OBJECTIVE: To estimate the prevalence of pediatric health care-associated
      infections (HAI) in Canadian acute care hospitals. METHODS: A point-prevalence
      study conducted in February 2002 in 25 hospitals across Canada. Information on
      HAI, utilization of antimicrobial agents and invasive devices, isolation
      precautions, and microbial etiology was collected. RESULTS: Nine hundred ninety
      seven children were surveyed. Ninety-one HAI were detected in 80 patients for a
      prevalence of 91 per 1000 patients surveyed. Bloodstream infections were the most
      common HAI (3% of patients; 34% of all HAI). The prevalence of patients with HAI
      was 8%, ranging from 0% in trauma/bum units to 19% in the pediatric intensive
      care units, and 27% in transplant units. By multivariate logistic regression
      analysis, having a central venous catheter (OR, 2.54; 95% CI, 1.46-4.40) or
      endotracheal tube with mechanical ventilation (OR, 2.59; 95% CI, 1.16-5.76) were
      independently associated with an HAI, as were being in isolation (OR, 2.90; 95%
      CI, 1.54-5.45), and receiving antimicrobial agents (OR, 9.27; 95% CI, 4.71
      18.52). CONCLUSION: In this first national point-prevalence study in Canada, the
      prevalence of HAI was similar to that reported in other industrialized countries.
      These data will also be useful to provide an estimate of the health burden of
      pediatric HAI in Canada.

PMID- 17433939
TI  - Hospital electronic medical record-based public health surveillance system
      deployed during the 2002 Winter Olympic Games.
AB  - BACKGROUND: Several computer biosurveillance systems are in place to detect
      events of public health (PH) significance; however, most lack access to timely
      and detailed patient-level data and investigation of alerts places a strain on PH
      resources. METHODS: Hospital-based infection control professionals led a multi
      disciplinary team to develop a computer rule-based system that relies on the
      patient's electronic medical record. The rules operated on HL7 messages
      transmitted by clinical computing systems and encompassed a variety of types of
      patient-level data, including laboratory test ordering and results, radiology
      ordering and reports, emergency room and outpatient clinic visits, and hospital
      admissions. Laboratory data were mapped to standard vocabularies, and radiology
      data were processed using natural language-processing algorithms before the rules
      were applied to filter for events of PH interest. For each rule, statistical
      process controls were applied to generate alerts when levels exceeded two
      standard deviations above the mean. The system was deployed at a large hospital
      in Salt Lake City during the 2002 Winter Olympic Games, and it was accessed 3
      times a day to perform surveillance. Daily reports were provided to local PH
      agencies after preliminary investigation of the alerts. RESULTS: Of the 24 rules
      monitored, 9 generated alerts on 11 different occasions. The only significant
      event of PH interest that was noted during the surveillance period was an
      increase in influenza during the Games. The positive predictive value of the
      rules varied with a high value (89%) noted for identification of pneumonia from
      chest radiograph reports by natural language-processing algorithms. CONCLUSIONS:
      With the assistance of a novel computer-based surveillance system linked to the
      electronic medical record that uses objective, quantifiable events and access to
      patient data, infection control practitioners could play a front-line role in
      biosurveillance and facilitate bidirectional communication with PH agencies.

PMID- 17433940
TI  - Outbreaks in neonatal intensive care units - they are not like others.
AB  - BACKGROUND: Outbreaks of health care-associated infections in neonatal intensive
      care units (NICUs) are frequent and have received more attention in medical
      literature than outbreaks from other types of intensive care units (ICUs). The
      objective of this systematic review was to identify differences between outbreaks
      of health care-associated infections in NICUs and other ICUs as reported to date
      in the medical literature. METHODS: Screening the outbreak database
      (http://www.outbreak-database.com), a systematic comparison of outbreaks was
      performed with the following categories: causing pathogen, type of infection,
      sources identified, and measures taken to stop the outbreak. RESULTS: Two hundred
      and seventy-six outbreaks were reported from NICUs and 453 from other ICU types.
      Enterobacteriaceae were significantly more often responsible for NICU outbreaks,
      whereas nonfermenting bacteria are more frequently identified in other ICU types.
      On average, 23.9 patients and 1.8 health care workers were involved in NICU
      outbreaks. Average mortality in NICU outbreak was 6.4% (1.5 newborns on average).
      In 48.6% of NICU outbreaks the authors were unable to identify the sources
      compared with 38.0% in other ICU outbreaks. The most important infection control
      measures were significantly more often implemented in NICUs than in other ICUs.
      CONCLUSIONS: Systematic outbreak analysis is essential for gaining insights into
      the control of NICU outbreaks.

PMID- 17433941
TI  - Risk factors for late-onset health care-associated bloodstream infections in
      patients in neonatal intensive care units.
AB  - BACKGROUND: There are few data comparing risk factors for catheter-related (CR)
      versus non-CR bloodstream infection (BSI) or for BSI caused by gram-positive
      versus gram-negative organisms. The aims of this study were to compare risk
      factors for CR versus non-CR BSI and to compare risk factors for BSI associated
      with gram-negative versus gram-positive organisms among infants hospitalized in
      two neonatal intensive care units (NICUs). METHODS: Data were collected
      prospectively over a 2-year period to assess risk factors among 2,935 neonates
      from two NICUs. RESULTS: Among all neonates, in addition to low birth weight and
      presence of a central venous catheter, hospitalization in NICU 1 (relative risk
      [RR]: 1.60, 95% confidence intervals [CI]: 1.14, 2.24) was a significant
      predictor of BSI. In neonates with a central catheter total parenteral nutrition
      (TPN) was a significant risk factor for BSI (RR: 4.69, 95% CI: 2.22, 9.87).
      Ventilator use was a significant risk factor for CR versus non-CR BSI (RR: 3.74,
      95% CI: 1.87, 7.48), and significantly more CR BSI were caused by gram-positive
      (77.1%) than by gram-negative organisms (61.4%), P = .03. CONCLUSIONS: This study
      confirmed that central venous catheters and low birth weight were risk factors
      for neonates with late-onset healthcare-associated BSI and further elucidated the
      potential risks associated with TPN and ventilator use in subgroups of neonates
      with BSI. Additional studies are needed to examine the incremental risk of TPN
      among infants with central venous catheters and to understand the link between CR
      BSI and ventilator use. Preventive strategies for BSI in neonates in NICUs should
      continue to focus on limiting the use of invasive devices.

PMID- 17433942
TI  - A 10-year prospective surveillance of nosocomial infections in neonatal intensive
      care units.
AB  - BACKGROUND: We report on nosocomial infections (NIs), causative organisms, and
      antimicrobial susceptibility patterns in neonates who were admitted to neonatal
      intensive care units (NICUs), and assess the performance of birth weight (BW) as
      a variable for risk-stratified NI rate reporting. METHODS: A prospective, 10-year
      follow-up, open cohort study that involved six Brazilian NICUs was conducted. The
      NI incidence rates were calculated using different denominators. RESULTS: Six
      thousand two hundred forty-three newborns and 450 NICU-months of data were
      available for analysis. This included 3603 NIs that occurred in 2286 newborns
      over 121,008 patient-days. The most frequent NIs were primary bloodstream
      infection (pBSI; 45.9%), conjunctivitis (12.1%), skin infections (9.6%), and
      pneumonia (6.8%). Only the pBSI (but not pneumonia or central venous catheter
      related pBSI) rate distribution differed significantly with varying BW. Gram
      negative rods (mainly Klebsiella sp. and Escherichia coli) were responsible for
      51.6% episodes of pBSI. Gram-positive organisms (mainly coagulase-positive
      staphylococci) accounted for 37.4%. Candida sp. was the fourth isolated organism.
      A high resistance to third-generation cephalosporins was recorded in K pneumoniae
      and E coli isolates. CONCLUSIONS: This report highlights the burden of NI, and
      identifies the major focus for future NI control and prevention programs. Except
      for pBSI, BW had a poor performance as a variable for risk-stratified NI rate
      reporting.

PMID- 17433943
TI  - Nosocomial infection in a neonatal intensive care unit: a prospective study in
      Taiwan.
AB  - BACKGROUND: We performed a prospective analysis to determine the prevalence of
      nosocomial infection and associated risk factors in our neonatal intensive care
      unit (NICU). METHODS: Data were collected prospectively on underlying diagnoses,
      therapeutic interventions/treatments, infections, and outcomes at 9 am every day
      from November 2004 through October 2005. Prevalence of nosocomial infection and
      infection site definitions were according to the National Nosocomial Infections
      Surveillance system of the Centers for Disease Control and Prevention. RESULTS:
      Among 528 infants enrolled, 60 (11.4%) had 97 nosocomial infections. The survival
      rate was 92%. The prevalence of nosocomial infections was 17.5%: bloodstream
      infection, 4.7%, clinical sepsis, 6.3%, pneumonia, 5.1%, urinary tract infections
      (UTIs), 0.7%, surgical site infection, 0.7%. Intervention-associated infection
      rate: central intravascular catheter-associated bloodstream infection, 13.7%, TPN
      associated bloodstream infection, 15.8%, ventilator-associated pneumonia, 18.6%,
      surgical site infection 13.7%, urinary catheter-associated UTI, 17.3%. Cut-off
      values of onset of central intravascular catheter-associated bloodstream
      infection and ventilator-associated pneumonia were 6 days and 10 days after
      intervention, respectively. Patients with a birth weight <1000 g (relative risk,
      11.8, 95% confidence interval, 7.66-18.18; P < .001) were at the greatest risk
      for nosocomial infection. CONCLUSIONS: This study revealed the high prevalence of
      nosocomial infections in NICU patients, and the urgent need for a national
      surveillance and more effective prevention interventions.

PMID- 17433944
TI  - Implementation of a pilot surveillance program for smaller acute care hospitals.
AB  - BACKGROUND: An infection control (IC) surveillance program for smaller (<100
      acute beds) hospitals was piloted for 18 weeks in 14 hospitals. The aim of the
      pilot stage was to test a theoretical program in the context in which it was to
      be implemented. METHOD: An evaluation framework was developed, outlining the
      program's intended activities for data collection, management, analysis,
      reporting, and use. This framework was used as a reference to interview each of
      the 12 IC nurses participating in the pilot stage. RESULTS: The preferred case
      finding methodologies were not uniformly applied. Management, analysis, and
      reporting of data were delayed because of infrequent and irregular IC hours and
      laboratory reporting. Reports were not always distributed to key persons.
      Specific action was only taken in response to the process (and not outcome)
      module reports. CONCLUSION: Discrepancies between the theoretical and actual
      implementation of a surveillance program for smaller hospitals were highlighted.
      The program will need to be revised before it is rolled out to all 89 eligible
      hospitals across Victoria.

PMID- 17433945
TI  - Surgical site infection surveillance for neurosurgical procedures: a comparison
      of passive surveillance by surgeons to active surveillance by infection control
      professionals.
AB  - ISSUE: Surveillance methods for surgical site infections (SSIs) range from
      patient self-report to active surveillance by infection control professionals
      (ICPs). Surgeon questionnaires surveying SSIs are typically suboptimal due to
      bias, lack of standardized criteria to diagnose infection, and poor response
      rate. Although concurrent surveillance of SSIs by ICPs at our medical center
      documented an incidence of 2.2 SSIs per 100 procedures, the neurosurgeons
      perceived a much higher rate of SSIs. PROJECT: The neurosurgeons provided a list
      of patients they had clinically identified with SSIs over a 7 month period. This
      list was compared with a line listing of SSIs independently identified by ICPs
      via concurrent surveillance utilizing the Centers for Disease Control and
      Prevention (CDC) definitions. RESULTS: A total of 766 procedures were performed.
      Active surveillance by ICPs detected 17 infections (2.2/100 procedures). Of the
      14 cases identified by the neurosurgeons, 3 did not meet the CDC definition of a
      nosocomial infection. The ICPs identified 6 SSIs not documented by the
      neurosurgeons. Compared to active surveillance by ICPs, the sensitivity and
      specificity of the neurosurgeon's identification of SSIs was 64% and 99.6%,
      respectively. The positive predictive value was 78.6% and the negative predictive
      value was 99.2%. LESSONS LEARNED: An active surveillance program is necessary for
      accurate identification of SSIs. The primary problem with passive surveillance by
      surgeons is failure to capture cases; surgeons missed 36% of cases compared to
      active surveillance by ICPs.

PMID- 17433946
TI  - Skin, hair, and other infections associated with visits to barber's shops and
      hairdressing salons.

PMID- 17433947
TI  - Routine preprocedure testing of patients in Japan for bloodborne pathogens?

PMID- 17433948
TI  - Atherosclerosis: the path from genomics to therapeutics.
AB  - Recent rapid advances in genomic tools and techniques hold great promise for
      transforming the practice of cardiovascular medicine. Resources including the
      Human Genome Project and the International HapMap project, major technological
      advances in high-throughput genotyping and methods of statistical analysis, and
      methods for high-throughput gene expression and small molecule profiling allow
      researchers to confront issues that will fundamentally change the practice of
      cardiovascular medicine during the 21st century. Genomic, proteomic, and
      metabolomic studies of complex cardiovascular diseases such as atherosclerosis
      will bridge epidemiology and basic biology, and promise increased understanding
      of cardiovascular disease processes. Genetic approaches applied to
      atherosclerosis will continue to identify genes and pathways involved in the
      predisposition to and pathophysiology of atherosclerosis. Gene expression
      profiling refines our understanding of the dynamic nature of the atherosclerotic
      vascular wall and promises discovery and validation of targets for therapeutic
      intervention. Opportunities to translate genetic, genomic, proteomic, and
      metabolomic information into cardiovascular clinical practice have never been
      greater, but their fruition requires validation in large independent cohorts,
      achieved only through collaborative effort. Their continued success will depend
      on ongoing cooperation within the cardiovascular research community.

PMID- 17433949
TI  - The final 10-year follow-up results from the BARI randomized trial.
AB  - OBJECTIVES: We sought to compare 10-year clinical outcomes in the BARI (Bypass
      Angioplasty Revascularization Investigation) trial patients who were randomly
      assigned to percutaneous transluminal coronary balloon angioplasty (PTCA) versus
      coronary artery bypass grafting (CABG). BACKGROUND: Angioplasty and bypass
      surgery have been compared in numerous studies, but long-term clinical outcomes
      are limited. METHODS: Symptomatic patients with multivessel coronary artery
      disease (n = 1,829) were randomly assigned to initial treatment with PTCA or CABG
      and followed up for an average of 10.4 years. Analyses were conducted on an
      intention-to-treat basis. RESULTS: The 10-year survival was 71.0% for PTCA and
      73.5% for CABG (p = 0.18). At 10 years, the PTCA group had substantially higher
      subsequent revascularization rates than the CABG group (76.8% vs. 20.3%, p <
      0.001), but angina rates for the 2 groups were similar. In the subgroup of
      patients with no treated diabetes, survival rates were nearly identical by
      randomization (PTCA 77.0% vs. CABG 77.3%, p = 0.59). In the subgroup with treated
      diabetes, the CABG assigned group had higher survival than the PTCA assigned
      group (PTCA 45.5% vs. CABG 57.8%, p = 0.025). CONCLUSIONS: There was no
      significant long-term disadvantage regarding mortality or myocardial infarction
      associated with an initial strategy of PTCA compared with CABG. Among patients
      with treated diabetes, CABG conferred long-term survival benefit, whereas the 2
      initial strategies were equivalent regarding survival for patients without
      diabetes.

PMID- 17433950
TI  - Pretreatment with intracoronary enalaprilat protects human myocardium during
      percutaneous coronary angioplasty.
AB  - OBJECTIVES: We tested the hypothesis that enalaprilat induces preconditioning
      (PC)-mimetic actions in patients with stable coronary artery disease. BACKGROUND:
      Angiotensin-converting enzyme (ACE) inhibitors increase the bioavailability of
      bradykinin, which induces cardiac PC. METHODS: Twenty-two patients undergoing
      coronary angioplasty were randomized to an intracoronary infusion of enalaprilat
      or placebo, followed 10 min later by a PC protocol. RESULTS: In control patients,
      the ST-segment shift was greater during the first inflation than during the
      second and third inflations, both on the intracoronary electrocardiogram (ECG)
      (21.0 +/- 2.8 mm vs. 13.0 +/- 2.0 mm and 13.0 +/- 2.0 mm, p < 0.05) and the
      surface ECG (16.0 +/- 4.0 mm vs. 10.0 +/- 2.0 mm and 9.0 +/- 2.0 mm, p < 0.05).
      In contrast, enalaprilat-pretreated patients showed no change in ST-segment shift
      during inflations on either the intracoronary or the surface ECG. During the
      first inflation, the ST-segment shift was significantly smaller in treated versus
      control patients. The chest pain score during the first inflation was also
      significantly smaller in treated patients versus control patients (33.0 +/- 6.0
      mm vs. 64.0 +/- 6.0 mm) and did not change in treated patients during the second
      and third inflations, whereas it decreased significantly in control patients. In
      a subset of 6 patients, enalaprilat increased coronary blood flow during
      infusion, but this effect dissipated before the beginning of angioplasty.
      CONCLUSIONS: Pretreatment with enalaprilat attenuates the manifestations of
      myocardial ischemia during angioplasty. This is the first in vivo evidence
      showing that an ACE inhibitor protects human myocardium, possibly via PC-mimetics
      actions, a novel property that might explain the cardioprotective actions of
      these drugs.

PMID- 17433951
TI  - Trends in outcomes after percutaneous coronary intervention for chronic total
      occlusions: a 25-year experience from the Mayo Clinic.
AB  - OBJECTIVES: The aim of our study was to examine the trends in procedural success,
      in-hospital, and long-term outcomes after percutaneous coronary intervention
      (PCI) for chronic total occlusions (CTO) over the last 25 years from a single PCI
      registry and to examine the impact of drug-eluting stents. BACKGROUND: The
      percutaneous treatment of CTO remains a major challenge. Past studies have used
      variable definitions of CTO, and there are limited data available from
      contemporary practice. METHODS: We evaluated the outcomes of 1,262 patients from
      the Mayo Clinic registry who required PCI for a CTO. The patients were divided
      into 4 groups according to the time of their intervention: group 1 (percutaneous
      transluminal coronary angioplasty era), group 2 (early stent era), group 3 (bare
      metal stent era), and group 4 (drug-eluting stent era). RESULTS: Procedural
      success rates were 51%, 72%, 73%, and 70% (p < 0.001), respectively, in the 4
      groups. In-hospital mortality (2%, 1%, 0.4%, and 0%, p = 0.009), emergency
      coronary artery bypass grafting (15%, 3%, 2%, and 0.7%, p < 0.001), and rates of
      major adverse cardiac events (8%, 5%, 3%, and 4%, p = 0.052) decreased over time.
      During follow-up, the combined end point of death, myocardial infarction, or
      target lesion revascularization, was significantly lower in the 2 most recent
      cohorts compared with those patients treated before (p = 0.001 for trend).
      Technical failure to treat the CTO was not an independent predictor of long-term
      mortality (hazard ratio 1.16 [95% confidence interval 0.90 to 1.5], p = 0.25).
      CONCLUSIONS: Procedural success rates for CTO have not improved over time in the
      stent era, highlighting the need to develop new techniques and devices. Compared
      with the prestent era, in-hospital major adverse cardiac events and 1-year target
      vessel revascularization rates have declined by approximately 50%.

PMID- 17433952
TI  - Increased Rho kinase activity in a Taiwanese population with metabolic syndrome.
AB  - OBJECTIVES: We sought to determine whether Rho kinase (ROCK) activity is
      increased in a Taiwanese population with metabolic syndrome (MetS). BACKGROUND:
      Recent studies suggest that ROCK may be involved in the pathogenesis of MetS, but
      clinical studies linking ROCK with MetS are lacking. METHODS: We studied 40
      Taiwanese subjects (60% men, mean age 55.5 +/- 5.6 years) who were diagnosed with
      MetS with National Cholesterol Educational Program Adult Treatment Panel III
      criteria and 40 age- and gender-matched control subjects. Subject demographics
      were recorded, and blood samples were obtained. RESULTS: Compared with control
      subjects, ROCK activity, as determined by phosphorylation of myosin binding
      subunit (MBS) in leukocytes, was greater in MetS subjects (mean phospho-MBS/MBS
      ratio 0.46 vs. 0.35, p = 0.002). A cutoff value for ROCK activity of 0.39
      predicted the presence of MetS with specificity and sensitivity rates of 70%.
      Plasma high-sensitivity C-reactive protein was greater (5.5 mg/l, 95% confidence
      interval [CI] 3.1 to 7.2 mg/l vs. 2.8 mg/l, 95% CI 1.1 to 3.9 mg/l, p = 0.01) and
      adiponectin was lower (4.9 microg/ml, 95% CI 3.2 to 6.1 microg/ml vs. 5.9
      microg/ml, 95% CI 4.2 to 7.5 microg/ml, p = 0.01) in MetS subjects compared with
      control subjects, but plasma levels of interleukin-6 and tumor necrosis factor
      alpha were not different (p > 0.05 for both). Body mass index, waist
      circumference, fasting glucose, high-sensitivity C-reactive protein, and
      triglyceride levels were associated with increased levels of ROCK activity. The
      risk of increased ROCK activity increased with the number of MetS components (p
      for trend <0.001). CONCLUSIONS: Rho kinase activity is increased in Taiwanese
      subjects with MetS and is associated with each component of MetS and markers of
      inflammation. These findings suggest that ROCK activity may be a novel
      serological marker of MetS.

PMID- 17433954
TI  - Seek and treat obstructive sleep apnea in heart failure.

PMID- 17433953
TI  - Influence of obstructive sleep apnea on mortality in patients with heart failure.
AB  - OBJECTIVES: This study sought to determine, in patients with heart failure (HF),
      whether untreated moderate to severe obstructive sleep apnea (OSA) is associated
      with a higher mortality rate than in patients with mild to no sleep apnea (M
      NSA). BACKGROUND: Obstructive sleep apnea is common in patients with HF and
      exposes the heart and circulation to adverse mechanical and autonomic effects.
      However, its effect on mortality rates of patients with HF has not been reported.
      METHODS: In a prospective study involving 164 HF patients with left ventricular
      ejection fractions (LVEFs) < or =45%, we performed polysomnography and compared
      death rates between those with M-NSA (apnea-hypopnea index [AHI] <15/h of sleep)
      and those with untreated OSA (AHI > or =15/h of sleep). RESULTS: During a mean
      (+/- SD) of 2.9 +/- 2.2 and a maximum of 7.3 years of follow-up, the death rate
      was significantly greater in the 37 untreated OSA patients than in the 113 M-NSA
      patients after controlling for confounding factors (8.7 vs. 4.2 deaths per 100
      patient-years, p = 0.029). Although there were no deaths among the 14 patients
      whose OSA was treated by continuous positive airway pressure (CPAP), the
      mortality rate was not significantly different from the untreated OSA patients (p
      = 0.070). CONCLUSIONS: In patients with HF, untreated OSA is associated with an
      increased risk of death independently of confounding factors.

PMID- 17433955
TI  - Pulmonary vein antral isolation using an open irrigation ablation catheter for
      the treatment of atrial fibrillation: a randomized pilot study.
AB  - OBJECTIVES: We sought to test how catheter ablation using an open irrigation
      catheter (OIC) compares with standard catheters for pulmonary vein antrum
      isolation. BACKGROUND: Open irrigation catheters have the advantage of delivering
      greater power without increasing the temperature of the catheter tip, which
      enables deeper and wider lesions without the formation of coagulum on catheters.
      METHODS: Catheter ablation was performed using an 8-mm catheter (8MC) or an OIC.
      Patients were randomized to 3 groups: 8MC; OIC-1, OIC with a higher peak power
      (50 W); and OIC-2, OIC with lower peak power (35 W). RESULTS: A total of 180
      patients were randomized to the 3 treatment strategies. Isolation of pulmonary
      vein antra was achieved in all patients. The freedom from atrial fibrillation was
      significantly greater in the 8MC and OIC-1 groups compared with the OIC-2 group
      (78%, 82%, and 68%, respectively, p = 0.043). Fluoroscopy time was lower in OIC-1
      compared with OIC-2 and 8MC (28 +/- 1 min, 53 +/- 2 min, and 46 +/- 2 min,
      respectively, p = 0.001). The mean left atrium instrumentation time was lower in
      the OIC-1 compared with the OIC-2 and 8MC groups (59 +/- 3 min, 90 +/- 5 min, and
      88 +/- 4 min, respectively, p = 0.001). However, there was a greater incidence of
      "pops" in the OIC-1 (100%, 0%, 0%, p < 0.001) along with higher incidences of
      pericardial effusion (20%, 0%, 0%, p < 0.001) and gastrointestinal complaints
      (17% in OIC-1, 3% in 8MC, and 5% in OIC-2, p = 0.031). CONCLUSIONS: Although
      there was a decrease in fluoroscopy and left atrium instrumentation time with the
      use of OIC at higher power, this setting was associated with increased
      cardiovascular and gastrointestinal complications.

PMID- 17433956
TI  - Association between C-reactive protein and recurrence of atrial fibrillation
      after successful electrical cardioversion: a meta-analysis.
AB  - OBJECTIVES: We conducted a systematic review and meta-analysis of observational
      studies to examine the association between baseline C-reactive protein (CRP)
      levels and the recurrence of atrial fibrillation (AF) after successful electrical
      cardioversion (EC). BACKGROUND: Current evidence links AF to the inflammatory
      state. Inflammatory indexes such as CRP have been related to the development and
      persistence of AF. However, inconsistent results have been published with regard
      to the role of CRP in predicting sinus rhythm maintenance after successful EC.
      METHODS: Using PubMed, the Cochrane clinical trials database, and EMBASE, we
      searched for literature published June 2006 or earlier. In addition, a manual
      search was performed using all review articles on this topic, reference lists of
      papers, and abstracts from conference reports. Of the 225 initially identified
      studies, 7 prospective observational studies with 420 patients (229 with and 191
      without AF relapse) were finally analyzed. RESULTS: Overall, baseline CRP levels
      were greater in patients with AF recurrence. The standardized mean difference in
      the CRP levels between the patients with, and those without AF was 0.35 units
      (95% confidence interval 0.01 to 0.69); test for overall effect z-score = 2.00 (p
      = 0.05). The heterogeneity test showed that there were significant differences
      between individual studies (p = 0.02; I(2) = 60.2%). Further analysis revealed
      that differences between the CRP assays possibly account for this heterogeneity.
      CONCLUSIONS: Our meta-analysis suggests that increased CRP levels are associated
      with greater risk of AF recurrence, although there was significant heterogeneity
      across the studies. The use of CRP levels in predicting sinus rhythm maintenance
      appears promising but requires further study.

PMID- 17433957
TI  - Atrial fibrillation and C-reactive protein: searching for local inflammation.

PMID- 17433958
TI  - Automated analysis of myocardial deformation at dobutamine stress
      echocardiography: an angiographic validation.
AB  - OBJECTIVES: We investigated the accuracy of automated analysis of myocardial
      deformation during dobutamine stress echocardiography (DSE). BACKGROUND: The time
      required for segmental measurement of strain rate imaging (SRI) limits its
      feasibility for quantification of DSE. METHODS: Myocardial deformation was
      assessed at DSE in 197 patients, 76 with and 61 without coronary artery disease
      (CAD) at angiography, and 60 at low risk of CAD. Automated deformation analysis
      was based on velocity gradient and segment length methods of measuring
      longitudinal motion within a region of interest tracked through the cardiac
      cycle. Results were compared with independent wall motion scoring (WMS). Patients
      were randomly divided; group A (n = 69) established optimal cutoffs for the
      parameters and group B (n = 68) tested their accuracy. RESULTS: The feasibility
      of WMS exceeded that of both SRI methods at rest and at peak stress. In group A,
      the area under the receiver-operating characteristics curve of the peak systolic
      strain rate was 0.90 by both methods, and the optimal cutoffs for detection of
      CAD were -1.3 (velocity gradient) and -1.2 s(-1) (segment length). The areas
      under the receiver-operating characteristics curves for end-systolic strain were
      less (0.87) by both methods, with respective cutoffs of 9% and 8%. In group B,
      the velocity and segment length methods had respective sensitivities of 87% and
      84% for SR, and 87% and 88% for end-systolic strain. Both significantly exceeded
      that of WMS in the same group (75%). CONCLUSIONS: Automated analysis of
      myocardial deformation at DSE is feasible and accurate, and may increase the
      sensitivity of expert conventional reading.

PMID- 17433959
TI  - Reduced aortic elasticity and dilatation are associated with aortic regurgitation
      and left ventricular hypertrophy in nonstenotic bicuspid aortic valve patients.
AB  - OBJECTIVES: This study sought to assess elasticity and dimensions of the aorta
      and their impact on aortic valve competence and left ventricular (LV) function in
      patients with a nonstenotic bicuspid aortic valve (BAV). BACKGROUND: Intrinsic
      pathology of the aortic wall is a possible explanation for reduced aortic
      elasticity and aortic dilatation in patients with BAVs, even in the absence of a
      stenotic aortic valve. The relationship between aortic wall elasticity, aortic
      dimensions, aortic valve competence, and LV function in patients with BAVs has
      not previously been studied with magnetic resonance imaging. METHODS: Magnetic
      resonance imaging was performed in 20 patients with nonstenotic BAVs (mean +/-
      SD, age 27 +/- 11 years) and 20 matched control patients. RESULTS: The BAV
      patients showed reduced aortic elasticity as indicated by increased pulse wave
      velocity in the aortic arch and descending aorta (5.6 +/- 1.3 m/s vs. 4.5 +/- 1.1
      m/s, p = 0.01; and 5.2 +/- 1.8 m/s vs. 4.3 +/- 0.9 m/s, p = 0.03, respectively),
      and reduced aortic root distensibility (3.1 +/- 1.2 x 10(-3) mm Hg(-1) vs. 5.6 +/
      3.2 x 10(-3) mm Hg(-1), p < 0.01). In addition, BAV patients showed aortic root
      dilatation as compared with control patients (mean difference 3.6 to 4.2 mm, p <
      or = 0.04 at all 4 predefined levels). Minor degrees of aortic regurgitation (AR)
      were present in 11 patients (AR fraction 6 +/- 8% vs. 1 +/- 1%, p < 0.01). The LV
      ejection fraction was normal (55 +/- 8% vs. 56 +/- 6%, p = 0.61), whereas LV mass
      was significantly increased in patients (54 +/- 12 g/m2 vs. 46 +/- 12 g/m2, p =
      0.04). Dilatation at the level of the aortic annulus (r = 0.45, p = 0.044) and
      reduced aortic root distensibility (r = 0.37, p = 0.041) correlated with AR
      fraction. Increased pulse wave velocity in the aortic arch correlated with
      increased LV mass (r = 0.42, p = 0.041). CONCLUSIONS: Reduced aortic elasticity
      and aortic root dilatation were frequently present in patients with nonstenotic
      BAVs. In addition, reduced aortic wall elasticity was associated with severity of
      AR and LV hypertrophy.

PMID- 17433960
TI  - How do I get a paper accepted?

PMID- 17433961
TI  - Visipaque (iodixanol) and hexabrix (ioxaglate) in renal insufficiency.

PMID- 17433962
TI  - Evaluation and comparison between visipaque (iodixanol) and hexabrix (ioxaglate)
      in coronary angiography.

PMID- 17433964
TI  - Is thrombus aspiration the appropriate "remedy"?

PMID- 17433966
TI  - Extended hours working in radiotherapy in the UK.
AB  - AIMS: To analyse extended hours working patterns within UK cancer centres and to
      assess alternatives to the normal 9.00 am to 5.00 pm working day. MATERIALS AND
      METHODS: Questionnaires were sent to 62 radiotherapy managers in June and July
      2005 to survey where extended hours working had been implemented, the objectives
      for using a longer working day and how departments organised their service
      issues, including staffing levels, costs and patients. This was followed by
      visits to six departments that were working extended hours. A second
      questionnaire sent to 60 radiotherapy physics managers in September 2005
      requested information for the hours of daily, monthly and annual megavoltage
      machine servicing and quality assurance (QA). A third questionnaire was
      distributed to all radiotherapy outpatients from four departments who attended on
      a single day of survey in 2005. It looked at patient preference for treatment
      hours. RESULTS: In total, 57 (92%) radiotherapy managers responded. Thirty-one
      departments (55%) were working extended hours, 22 (39%) had short-term experience
      and three (5%) departments had no experience. Increasing capacity to reduce
      waiting lists was the main reason for working extended hours. The additional
      hours were predominantly worked by radiographers, with little or no support from
      the other department disciplines. The servicing and QA spreadsheet was returned
      by 53% (n=32) of physicists. The average amount of servicing and Quality
      Assurance (QA) work being scheduled out of hours in each department was 35% (0
      100%). The patient questionnaire was completed by 470 patients. When asked if
      patients would want to come to a reasonable appointment time outside of the
      normal working day, 29% (n=136) said 'yes' and 12% (n=55) were unsure.
      CONCLUSION: It was concluded that two shifts covering an 11.5 h working day is a
      robust alternative to the normal working day, taking into consideration efficient
      use of radiographers and patient preference for out of hours appointments.

PMID- 17433967
TI  - Three-year single institution audit on transfusion requirements in oncology
      patients.
AB  - AIMS: To assess recent developments in the use of transfusions. MATERIALS AND
      METHODS: Data from hospital-based sources were condensed in a single spread sheet
      covering 1611 transfusions of a total of 881 patients together with data on
      25,264 treatment sessions in 6137 patients within a time period between 1 August
      2001 and 31 July 2004. RESULTS: Our audit showed an increase in transfusions of
      25% in 3 years. This was accompanied by an increased threshold for transfusions,
      as shown by a significant rise in mean haemoglobin trigger levels from 8.53 to
      8.86 g/dl (P<0.001) as well as an increase in treatment sessions and patient
      numbers - especially for chemotherapy or combinations of chemotherapy and
      radiotherapy. The highest transfusion rates and also the greatest increments
      occurred in patients with carcinoma of the ovary, lung and pancreas. Within these
      groups, treatment regimens as well as treatment lines were additional predictive
      factors. CONCLUSIONS: This audit gives a detailed view on rising trends in
      transfusion requirements and, in light of anticipated restrictions on resources,
      it identifies high-risk areas, where the use of alternatives, such as
      erythropoietin, could be considered.

PMID- 17433968
TI  - The prognostic value of anaemia at different treatment times in patients with
      locally advanced head and neck cancer treated with surgery and postoperative
      radiotherapy.
AB  - AIMS: We report a retrospective mono-institutional analysis of anaemia (< 12
      g/dl) at different treatment times (preoperative, postoperative, before
      radiotherapy and nadir levels during radiotherapy) in head and neck cancer
      patients treated with surgery and postoperative radiotherapy. The study objective
      was to determine whether, and at which time points, anaemia had a significant
      effect on the end points overall survival and local recurrence-free survival
      (LRFS). MATERIALS AND METHODS: The end points for the statistical analysis in 130
      patients were LRFS and overall survival. A univariate analysis (Log-rank test)
      was carried out on the following variables with potential end point-related
      impact: gender, T, N, G, American Joint Committee on Cancer (AJCC) stage, tumour
      site, resection status, overall treatment time (OTT), radiotherapy treatment time
      (RTT) and preoperative, postoperative, pre-radiotherapy and nadir levels of
      haemoglobin during radiotherapy. Individual variables with a significant effect
      (P=0.05) were then subjected to multivariate Cox regression analysis. RESULTS:
      The median overall survival was 59 months. The univariate analysis showed that
      AJCC stage (P=0.0268), resection status (P=0.0407), preoperative haemoglobin
      level (P=0.0087), postoperative haemoglobin level (P=0.0035), RTT (P=0.0042) and
      OTT (P=0.0343) significantly influenced overall survival. OTT (P=0.0130) and
      postoperative haemoglobin (P=0.0243) had a significant effect on LRFS. The
      multivariate Cox regression analysis showed postoperative haemoglobin < 12 g/dl
      and OTT>100 days to be independent negative prognostic factors for both end
      points. CONCLUSIONS: Postoperative acute anaemia < 12 g/dl and an OTT>100 days
      were independent negative prognostic factors for LRFS and overall survival in
      patients with head and neck cancer treated with surgery and postoperative
      radiotherapy.

PMID- 17433969
TI  - Positron emission tomography in oncology: a review.
AB  - Positron emission tomography is an evolving imaging tool that is becoming
      increasingly available for use in clinical practice. This overview will look at
      the current evidence for the use of positron emission tomography in imaging
      different tumour types and the different radiotracers that are either available
      or being evaluated in an investigational setting.

PMID- 17433970
TI  - Vitamin E protects against the development of radiation-induced pulmonary
      fibrosis in rats.
AB  - AIMS: To investigate whether the application of vitamin E with or without
      pentoxifylline could modify the development of radiation-induced pulmonary
      fibrosis. MATERIALS AND METHODS: Wistar albino rats were supplemented with either
      vitamin E or pentoxifylline or with both vitamin E and pentoxifylline after a
      single dose of 14 Gy thoracic irradiation. Supplementation was started the day
      after irradiation and continued until the rats were sacrificed. As a quantitative
      end point, the extent of fibrosis was evaluated with a scale from 0 (normal lung)
      to 8 (total fibrous obliteration of the field) at pathological examination of the
      lung tissue. RESULTS: A significant reduction in fibrosis was obtained in the
      group of rats supplemented with vitamin E with or without pentoxifylline, when
      compared with the group that had irradiation only. CONCLUSION: This experimental
      study showed that vitamin E supplementation immediately after irradiation
      protected rats against radiation-induced pulmonary fibrosis. The combination with
      pentoxifylline was more effective, although pentoxifylline itself had limited
      efficacy, which was not statistically significant.

PMID- 17433971
TI  - Mechanisms and management of non-islet cell tumour hypoglycaemia in
      gastrointestinal stromal tumour: case report and a review of published studies.
AB  - Tumour-related hypoglycaemia is a rare paraneoplastic phenomenon most frequently
      occurring with insulinomas, but also associated with non-islet cell tumours. It
      has been observed in a range of tumour types, but recently a small number of
      cases have been described in association with gastrointestinal stromal tumours.
      We describe a further case of a patient with gastrointestinal stromal tumour that
      was complicated by non-islet cell tumour hypoglycaemia, and discuss the
      mechanisms and management of non-islet cell tumour hypoglycaemia in the context
      of gastrointestinal stromal tumour.

PMID- 17433972
TI  - A small proportion of glioblastoma patients are probably eligible for
      concomitant/adjuvant temozolomide.

PMID- 17433973
TI  - The staging system of metastatic lymph node ratio in gastric cancer.

PMID- 17433975
TI  - Future directions in MR imaging of the female pelvis.
AB  - New technology continues to change the field of MR imaging. This article
      describes select areas of technical development that are likely to have an
      increasing clinical impact on MR imaging of the female pelvis, including high
      field imaging, parallel imaging, contrast agents, diffusion-weighted imaging and
      spectroscopy, and MR-guided intervention.

PMID- 17433976
TI  - MR imaging of benign uterine disease.
AB  - MR provides excellent depiction of the female pelvic anatomy and has become the
      imaging modality of choice for the accurate diagnosis of numerous benign
      gynecologic conditions. Detection and characterization of leiomyomata and
      adenomyosis is performed routinely at many centers, and MR plays an important
      role in stratifying patients into appropriate treatment options. MR imaging is
      also uniquely well suited to the evaluation of gynecologic conditions that occur
      during pregnancy and in the postpartum period. This article describes MR
      protocols and the typical findings of various benign conditions of the uterine
      corpus and cervix, including congenital anomalies, leiomyomas, adenomyosis, and
      complications related to pregnancy.

PMID- 17433977
TI  - MR imaging of malignant uterine disease.
AB  - The role of MR imaging in the diagnosis and management of patients who have
      uterine malignancy continues to evolve. MR imaging has been shown to be effective
      for preoperative characterization and staging of endometrial and cervical
      carcinoma, and for the evaluation of posttreatment changes and recurrent disease.
      Because of its potential to provide detailed information about local extent and
      metastatic disease, MR imaging has enormous potential to help triage patients to
      appropriate treatment groups and provide imaging surveillance after therapy. This
      article reviews the MR imaging technique and the imaging characteristics of
      malignant disease of the uterine corpus and cervix.

PMID- 17433978
TI  - MR imaging evaluation of the adnexa.
AB  - MR imaging has become an important tool in the evaluation of patients with
      adnexal disease, and its role continues to evolve. Some benign entities can be
      diagnosed by MR imaging with a high grade of confidence, such as teratomas,
      endometriomas, simple and hemorrhagic cysts, fibromas, and hydrosalpinx. In cases
      of malignant lesions, MR imaging may be more accurate than other modalities for
      lesion characterization, staging, and follow-up.

PMID- 17433979
TI  - MR imaging evaluation of acute abdominal pain during pregnancy.
AB  - MR imaging enables diagnosis of a variety of maternal diseases presenting as
      acute abdominal pain in pregnant patients. MR imaging is a valuable complement to
      ultrasound in the determination of the exact etiology of acute abdominal pain,
      and it is important for the radiologist to recognize the MR imaging appearance of
      common causes of acute abdominal pain during pregnancy. This article reviews the
      MR imaging technique and findings of various abnormalities causing acute
      abdominal pain in pregnant patients.

PMID- 17433980
TI  - Fetal MR imaging.
AB  - Ultrasonography is the primary prenatal screening modality used in the evaluation
      of the fetus and the maternal pelvis. However, fetal MR imaging plays a
      complementary role to prenatal ultrasound in the evaluation of the fetus with
      suspected abnormalities. MR imaging's role includes confirming or excluding
      possible lesions, defining their full extent, aiding in their characterization,
      and demonstrating other associated abnormalities. As newer techniques such as
      diffusion imaging, MR spectroscopy, and functional studies are used more widely,
      it is hoped that additional information will be made available by this modality
      to physicians evaluating and taking care of fetuses.

PMID- 17433981
TI  - MR imaging evaluation of the pelvic floor for the assessment of vaginal prolapse
      and urinary incontinence.
AB  - Pelvic MR imaging using the combination of motion-insensitive T2-weighted single
      shot fast spin echo and high soft tissue resolution standard T2-weighted fast
      spin echo techniques has helped to identify soft tissue abnormalities that
      directly correlate with the clinical and intraoperative findings related to
      pelvic floor prolapse. In particular, the authors have shown that pelvic MR
      imaging has the ability to identify changes related to uterosacral ligament
      disruption and to document the corrective changes after surgical repair of this
      ligament. In the future, pelvic MR imaging is expected to play a progressively
      larger role in preoperative planning for complex or uncertain cases and for more
      detailed evaluation of repair in cases that do not show good symptomatic
      response. Pelvic MR imaging should also help to document and advance knowledge of
      surgical repair methodology.

PMID- 17433982
TI  - MR imaging of the female pelvis at 3T.
AB  - The recent development of the transmit-receive body coil and the dedicated torso
      phased-array radio frequency receive coil for 3.0T MR imaging systems has
      promoted a move toward higher-field, whole-body MR imaging, including pelvic MR
      imaging. The female pelvis is an anatomic area that may benefit particularly from
      the advantages of high-field systems. In this article, the authors present their
      initial experience with the optimization of sequences for MR imaging of the
      female pelvis at 3.0T, and include a short description of parallel imaging. They
      compare some of the physical properties of 1.5T and 3.0T, discuss some of the
      challenges during sequence optimization for the female pelvis at 3.0T, and give
      examples of female pelvic abnormalities.

PMID- 17433985
TI  - Overview: history, anatomy, timing, and results of complete atrioventricular
      canal.
AB  - The past 50 years have been marked by major advances in the care of children with
      complete atrioventricular canal defects. There have been important contributions
      from surgeons, cardiologists, and pathologists to provide us with our current
      understanding of the anatomy of atrioventricular canal defects and excellent
      surgical outcomes. In this monograph we will discuss the surgical contributions
      of Lillehei, Kirklin, McGoon, Maloney, Trusler, Wilcox, and Nunn. The
      improvements in outcomes achieved by these surgeons were made possible by the
      pathology and anatomy clarifications provided by Lev, Rastelli, and Anderson.

PMID- 17433986
TI  - Atrioventricular canal: single-patch technique.
AB  - Complete atrioventricular septal defects have been repaired at the Medical
      University of South Carolina for the past 25 years using the "single-patch
      technique" as first described by the Mayo Clinic group in 1968. In this
      technique, the single atrioventricular valve is separated into left (mitral) and
      right (tricuspid) components by dividing the superior and inferior bridging
      leaflets back to the annulus. A single patch of bovine pericardium is sutured to
      the right ventricular aspect of the ventricular septum, the previously divided
      valve leaflets are resuspended to the patch, the "cleft" in the left-sided valve
      is closed with interrupted sutures, and the atrial component of the defect closed
      by suturing the patch to the atrial septum with a continuous suture. Since 1995,
      there have been no operative deaths in the 88 consecutive infants undergoing this
      repair in our institution. Nine patients (10.2%) have required reoperation for
      severe mitral regurgitation. While the issue of operative mortality in patients
      undergoing single-patch repair of complete atrioventricular septal defect has
      largely been eliminated, residual or recurrent mitral regurgitation continues to
      be a problem.

PMID- 17433987
TI  - The double patch repair for complete atrioventricularis communis.
AB  - This article is a review of our experience with the two-patch repair of complete
      atrioventricularis communis. From October 1988 through December 2005, 222 infants
      and children underwent surgery. There were six early (2.7%) and six late (2.7%)
      deaths. Reoperation was required in 22 patients (10%) for residual or recurrent
      mitral regurgitation or stenosis, subaortic stenosis, repair of a ventricular
      septal defect with or without pulmonary stenosis, placement of a right heart
      valved conduit, and/or placement of a permanent cardiac pacemaker. All patients
      survived second operations and no child required early or late mitral valve
      replacement. The two-patch repair is a reliable surgical technique resulting in
      low mortality and a low need for reoperation.

PMID- 17433988
TI  - Atrioventricular canal: modified single patch technique.
AB  - A single surgeon experience using a modified single patch technique for the
      repair of 128 patients with complete atrioventricular canal is presented. Thirty
      day mortality was 1.6%. Follow-up of these patients has shown no incidence of
      significant residual ventricular septal defect, a 2.3% incidence of reoperation
      on the mitral valve, and no instances of left ventricular outlet obstruction
      requiring resection in the follow-up period. Comparisons are drawn between these
      results and the author's own experience with repair of complete atrioventricular
      canal using a two-patch technique (46 cases) and repair of partial
      atrioventricular canal (126 cases) to shed light on late valve function and left
      ventricular outlet obstruction in all groups.

PMID- 17433989
TI  - Complex atrioventricular canal.
AB  - Complex forms of atrioventricular (AV) canal (C) such as; AVC with left
      ventricular outflow tract obstruction, tetralogy of Fallot with complete AVC,
      double orifice left AV valve, unbalanced complete AVC, and single ventricle
      patients with common AVC valve require careful preoperative planning and special
      techniques. This review will explore these technical modifications and outcomes
      for repair of complex variants of AVC. Optimal results will be achieved using an
      individually tailored approach that is guided by careful evaluation of the
      preoperative studies, precise operative technique, and intraoperative assessment
      of the reconstructed AV valve, as well as a willingness to re-intervene should
      the postoperative course not proceed as anticipated.

PMID- 17433990
TI  - Partial atrioventricular canal: pitfalls in technique.
AB  - Partial atrioventricular (AV) canal represents approximately 25% of all AV septal
      defects. While often grouped with secundum ASD from the perspective of
      cardiopulmonary physiology, clinical presentation, and timing of surgical
      correction, their optimal management truly requires an understanding of their
      anatomic similarities to other forms of common AVC defects. By most measures,
      outcomes for surgical management of partial AV canal has improved over the last
      four decades, though some aspects of these defects continue to pose important
      challenges. Current experience has witnessed the reduction in early mortality and
      only rare complete heart block. Left AV valve dysfunction remains the most common
      indication for reoperation (10%) with LVOT stenosis the next most common reason
      (10% to 15% incidence, 5% to 10% reoperation rate). It is important to understand
      in this population that postoperative left AV valve problems and LVOT stenosis
      may be intimately linked, both from an etiologic standpoint, and with respect to
      their management.

PMID- 17433991
TI  - Intraoperative echocardiography for atrioventricular canal: decision-making for
      surgeons.
AB  - Intraoperative echocardiography has become a standard patient management tool in
      the assessment of the patient undergoing surgical repair of a congenital cardiac
      defect. Over the past 15 years transesophageal echocardiography has emerged as an
      integral part of the intraoperative assessment of the congenital cardiac surgery
      patient. The important role of intraoperative echocardiography is largely because
      of its ability to define complex anatomy, identify functional abnormalities, and
      recognize flow disturbances at the time of surgical repair. Intracardiac defects
      are particularly suited to the strengths of intraoperative transesophageal
      echocardiography because of the unobstructed windows that can be obtained. This
      article focuses on how intraoperative echocardiography can guide surgical
      decision-making in the patient undergoing repair of an atrioventricular canal
      defect.

PMID- 17433993
TI  - The helical ventricular myocardial band of Torrent-Guasp.
AB  - We live in an era of substantial progress in understanding myocardial structure
      and function at genetic, molecular, and microscopic levels. Yet, ventricular
      myocardium has proven remarkably resistant to macroscopic analyses of functional
      anatomy. Pronounced and practically indefinite global and local structural
      anisotropy of its fibers and other ventricular wall constituents produces
      electrical and mechanical properties that are nonlinear, anisotropic, time
      varying, and spatially inhomogeneous. The helical ventricular myocardial band of
      Torrent-Guasp is a revolutionary new concept in understanding global, 3
      dimensional, functional architecture of the ventricular myocardium. This concept
      defines the principal, cumulative vectors, integrating the tissue architecture
      (ie, form) and net forces developed (ie, function) within the ventricular mass.
      The primary purpose of this review is to emphasize the importance of this
      concept, in the light of collaborative efforts to establish an integrative
      approach, defining ventricular form and function by linking across multiple
      scales of biological organization, as explained in the ongoing Physiome project.
      Because one of the most important scientific missions in this century is
      integration of basic research with clinical medicine, we believe that this
      knowledge is not of merely academic importance, but is also the essential
      prerequisite in clinical evaluation and treatment of different heart diseases.

PMID- 17433994
TI  - Potential implications of the helical heart in congenital heart defects.
AB  - The anatomic and functional observations made by Francisco Torrent-Guasp, in
      particular his discovery of the helical ventricular myocardial band (HVMB), have
      challenged what has been taught to cardiologists and cardiac surgeons over
      centuries. A literature debate is ongoing, with interdependent articles and
      comments from supporters and critics. Adequate understanding of heart structure
      and function is obviously indispensable for the decision-making process in
      congenital heart defects. The HVMB described by Torrent-Guasp and the potential
      impact on the understanding and treatment of congenital heart defects has been
      analyzed in the following settings: embryology, ventriculo-arterial discordance
      (transposition of great arteries), Ebstein's anomaly, pulmonary valve
      regurgitation after repair of tetralogy of Fallot, Ross operation, and other
      congenital heart defects. The common structural spiral feature is only one of the
      elements responsible for the functional interaction of right and left ventricles,
      and understanding the form/function relationship in congenital heart defects is
      more difficult than for acquired heart disease because of the variety and
      complexity of congenital heart defects. Individuals involved in the care of
      patients with congenital heart defects have to be stimulated to consider further
      investigations and alternative surgical strategies.

PMID- 17433995
TI  - Pathophysiologic implications of the helical ventricular myocardial band:
      considerations for right ventricular restoration.
AB  - This chapter describes the structure/function relationships of the right
      ventricle (RV), and shows how the geometry of the helical ventricular myocardial
      band model defines spatial geometry of the free wall and septum that underlie
      dynamic action. Myocardial fiber orientation is the keynote to performance in
      health and disease. The transverse geometry of the RV free wall allows
      constriction (bellows-type motion), whereas oblique septal fiber orientation and
      midline septal position is essential for ventricular twisting, the vital
      mechanism for RV ejection against increased pulmonary vascular resistance.
      Therefore, the septum is considered "the lion or motor of RV performance."
      Distortion of such normal structure/function relationships underlies the
      pathophysiologic mechanisms of RV failure. Operative methods that restore normal
      myocardial fiber orientation are described to outline evolving surgical
      techniques for the surgical treatment of RV failure.

PMID- 17433996
TI  - How are the myocytes aggregated so as to make up the ventricular mass?
AB  - Of late, it has become fashionable in the surgical literature to describe the
      ventricular mass as though arranged in the form of a continuous myocardial band,
      which starts at the aorta and ends at the pulmonary trunk. On the basis of this
      concept, its supporters have produced revisionist accounts of cardiac development
      and ventricular function, as well as using it as the basis for proposed surgical
      maneuvers. They seem unaware, however, that the original concept itself has never
      been supported by independent anatomic studies, while, to the best of our
      knowledge, they have not themselves performed anatomic investigations to prove
      its substance. Furthermore, the current proponents of the "unique myocardial
      band" ignore a large body of previous anatomic study which showed that the
      ventricular mass is arranged in the form of a modified blood vessel, with each
      myocyte anchored to its neighbor within a 3-dimensional myocardial mesh, rather
      than being arranged in a fashion analogous to skeletal muscles, with discrete
      origins and insertions of myocardial bands or tracts. In this review, we
      summarize the evidence showing that there are no anatomic structures within the
      ventricular myocardium that permit it to be unraveled in systematic fashion so as
      to produce the purported myocardial band. We also re-visit our own previous
      investigations, which supported the conventional approach, namely that the
      myocytes are aggregated together within a supporting fibrous matrix in the form
      of a 3-dimensional meshwork.

PMID- 17433997
TI  - The ventricular myocardial band of Torrent-Guasp - the controversy: an editorial.

PMID- 17433998
TI  - Aortic valve sparing and restoration with autologous pericardial leaflet
      extension is an effective alternative in pediatric patients.
AB  - We sought to evaluate the durability and efficacy of aortic valve repair with
      autologous pericardial leaflet extension in children. From 1997 through 2006, 54
      patients underwent aortic valve repair with autologous pericardial leaflet
      extension at a mean age 8.4 +/- 5.3 years (range, 0 to 17 years). Primary
      endpoints were early and late mortality, freedom of reoperation, and late valve
      function. Thirty-day and late mortality were one in 54 (1.8%) and two in 53
      (3.7%), respectively. There were seven re-operations in six patients, and one
      patient was re-operated twice. Re-operations were re-repairs in four cases and
      replacements in three cases. The mean interval between original repair and re
      operation was 4.3 +/- 2.5 years. Mean severity grade of post-repair
      intraoperative aortic regurgitation (AR) was 0.3 (range, grade 0 to 4). At late
      follow-up, 87.7% of all patients had no AR or only a trace (grade 0-1). Seven
      patients (12.9%) had mild AR (grade 2-3) and none severe (grade 4); 94.4% had no
      aortic stenosis or only a trace (grade 0-1), 5.5% had mild (grade 2-3), and none
      severe. This technique delays potential complications from other approaches to
      valve pathology and allows a normal growth of the aortic annulus. Although, our
      data show that this technique has a low mortality and morbidity, more studies are
      needed to elucidate durability and late outcome.

PMID- 17433999
TI  - Mitral/systemic atrioventricular valve repair in congenital heart disease.
AB  - Because there is no ideal substitute for the mitral or the systemic
      atrioventricular valve (SAVV) in a patient of any age, repair is the optimal
      treatment for important congenital or acquired mitral/SAVV disease. Valve repair
      techniques have evolved to the point where early repair may be offered to
      asymptomatic patients with favorable anatomy. The indications for operation
      depend on the presence or absence of symptoms and the physiologic consequences of
      mitral/SAVV pathology. Concomitant arrhythmia surgery may be appropriate in
      selected cases. Surgical outcomes are good to excellent when appropriate
      techniques are used. Repair of congenital SAVV abnormalities is safe and durable
      in many patients.

PMID- 17434000
TI  - Tricuspid valve repair for hypoplastic left heart syndrome and the failing right
      ventricle.
AB  - Tricuspid valve regurgitation in patients with hypoplastic left heart syndrome is
      a cause of significant morbidity and mortality. Due to the multifactorial nature
      of its etiology, repair of the tricuspid valve may not always address the
      underlying problem and fail to improve late outcome. The role of tricuspid valve
      repair in this condition was examined in a series of patients with severe
      regurgitation following a Norwood procedure. The influence of surgical technique
      and right ventricular function were assessed in relation to late survival and
      tricuspid valve function. Tricuspid valve repair was successfully performed in
      the majority of patients and contributed to improved late outcomes. However,
      patients with an initially successful repair but significant right ventricular
      dysfunction tended to do poorly and the function of the valve often continued to
      deteriorate. Those with preserved ventricular function, even with continued
      tricuspid regurgitation, fared much better and achieved good results with
      additional attempts at repair.

PMID- 17434001
TI  - Surgical management of Ebstein's anomaly.
AB  - Ebstein's malformation is a congenital anomaly of the tricuspid valve and right
      ventricle. Surgical repair of Ebstein's anomaly improves functional class and
      exercise tolerance, eliminates right-to-left intracardiac shunting (if present),
      and reduces the incidence of supraventricular tachyarrhythmias. As a result,
      quality of life and survival are improved. Because of the variable degree of
      malformation present, repair is predicated on favorable anatomic factors, most
      importantly the arrangement of the anterior leaflet of the tricuspid valve. When
      anatomic derangements threaten a durable tricuspid valve repair, valve
      replacement with protection of the conduction tissue and right coronary artery
      should be performed. The vast majority of patients can undergo a biventricular
      repair. The application of the bidirectional cavopulmonary anastomosis is
      reserved for patients with poor right ventricular function. Freedom from
      reoperation after tricuspid valve repair is similar when compared with valve
      replacement. In the current era, overall early mortality after surgical repair in
      children and adults has fallen to less than 3% in experienced centers. Surgical
      treatment of the symptomatic neonate remains a significant challenge, with
      approaches that include either a biventricular or single ventricle algorithm.

PMID- 17434002
TI  - Management of neonatal Ebstein's anomaly.
AB  - The presentation of Ebstein's anomaly (ventricular displacement of the tricuspid
      valve, especially septal and posterior leaflets) in the neonatal period is
      distinguished from that in later life by a much higher mortality, due in part to
      the pre-existing elevation in pulmonary vascular resistance. Surgery in the
      neonatal period has previously focused on palliation and conversion to single
      ventricle physiology. Successful two-ventricle repair with good clinical results
      can safely be performed in the neonatal period.

PMID- 17434003
TI  - When reconstruction fails or is not feasible: valve replacement options in the
      pediatric population.
AB  - Valvular pathology in infants and children poses numerous challenges to the
      pediatric cardiac surgeon. Without question, valvular repair is the goal of
      intervention because restoration of valvular anatomy and physiology using native
      tissue allows for growth and a potentially better long-term outcome. When
      reconstruction fails or is not feasible, valve replacement becomes inevitable.
      Which valve for which position is controversial. The goal of this article is to
      address valve replacement options for all four valve positions within the
      pediatric population. We will draw from our institutional experience and review
      current literature to support our preferences.

PMID- 17434004
TI  - Cardiac surgeon's primer: tissue-engineered cardiac valves.

PMID- 17434005
TI  - Evolving anatomic and electrophysiologic considerations associated with Fontan
      conversion.
AB  - The principles of Fontan conversion with arrhythmia surgery are to restore the
      cardiac anatomy by converting the original atriopulmonary connection to a total
      cavopulmonary artery extracardiac connection and treat the underlying atrial
      arrhythmias. Successful outcomes of this procedure are dependent on a thorough
      understanding of several factors: the patient's fundamental diagnosis of single
      ventricle anatomy, the resultant cardiac configuration from the original
      atriopulmonary Fontan connection, right atrial dilatation that leads to atrial
      flutter or fibrillation, and associated congenital cardiac anomalies. The purpose
      of this article is to present some of the more challenging anatomic and
      electrophysiologic problems we have encountered with Fontan conversion and
      arrhythmia surgery and the innovative solutions we have used to treat them. The
      cases reviewed herein include: takedown of a Bjork-Fontan modification, right
      ventricular hypertension and tricuspid regurgitation after atriopulmonary Fontan
      for pulmonary atresia and intact ventricular septum, takedown of atrioventricular
      valve isolation patch for right-sided maze procedure, resultant hemodynamic
      considerations leading to intraoperative pulmonary vein stenosis after Fontan
      conversion, unwanted inferior vena cava retraction during the extracardiac
      connection, right atrial cannulation in the presence of a right atrial clot,
      distended left superior vena cava causing left pulmonary vein stenosis, dropped
      atrial septum, and the modified right-sided maze procedure for various single
      ventricle pathology. Since 1994 we have performed Fontan conversion with
      arrhythmia surgery on 109 patients with a 0.9% mortality rate. We attribute our
      program's success in no small measure to the strong collaborative efforts of the
      cardiothoracic surgery and cardiology teams.

PMID- 17434006
TI  - Expanding the hybrid concept in congenital heart surgery.
AB  - Hybrid procedures in congenital heart surgery are evolving. Some have matured,
      such as the hybrid stage I, and require closer large-scale scrutiny before they
      can be integrated into mainstream pediatric cardiac surgery. Others are still
      evolving along with newer technologies and advances in interventional cardiology.
      This review provides a snapshot at the current state of hybrid procedures in
      congenital heart surgery.

PMID- 17434008
TI  - Update on therapeutic monoclonal antibodies.
AB  - Monoclonal antibodies are among the most important class of drugs introduced into
      the therapeutic armamentarium since the introduction of antimicrobials in the
      1930s. The first therapeutic monoclonal antibody, the anti T-cell monoclonal
      antibody OKT4, was licensed in 1986. Since then, 18 additional antibodies have
      been licensed in the US, with many more in the pipeline. Before 1986, many
      monoclonal antibodies were available for laboratory studies, notably to identify
      specific cells in the blood and tissues. This is best illustrated by the cluster
      designation (CD) system for antigens present on hematopoietic cells, now
      numbering over 200.

PMID- 17434010
TI  - A new era in psychiatric genetics?

PMID- 17434011
TI  - Extreme chipping: addiction to a high-fat diet?

PMID- 17434012
TI  - Cultural competence: an international perspective.

PMID- 17434013
TI  - Range of published estimates of venous thromboembolism incidence in young women.
AB  - OBJECTIVE: This review was conducted to show the full range of incidence
      estimates published for venous thromboembolism (VTE) in women depending on study
      design and to suggest a more reliable estimate for women of reproductive age.
      METHODS: A literature search was performed to identify studies on the incidence
      of VTE in women. Incidence rates were compiled from studies with different
      methodologies and varying methodological quality. Algorithms were used to
      estimate VTE incidence from more reliable studies in young women. RESULTS AND
      DISCUSSION: The literature shows two levels of VTE incidence rates:
      community/cohort studies and database studies. The estimated VTE incidence for
      women of reproductive age was 5.5-13.5 and 3.8-12.2 in community and cohort
      studies, respectively, but only 0.7-3.8 per 10,000 women-years (WY) in database
      studies. This difference is probably attributable to methodological problems
      associated with some database studies. CONCLUSION: The VTE incidence in women of
      reproductive age is likely to be in the range of 5-10 per 10,000 WY. These rates
      for the background incidence are clearly higher than the reference figures that
      are often utilized in the comparison with users of hormonal contraception (0.5-1
      VTE per 10,000 WY).

PMID- 17434014
TI  - Once-a-month contraceptive pills in China: a review of available evidence.
AB  - OBJECTIVE: A review of evidence was conducted to assess the safety, effectiveness
      and continuation of once-a-month contraceptive pills. METHODS: Papers were
      identified by electronic searches in Chinese and international databases and
      manual searches of Chinese journals and index of family planning literature. Data
      on pharmacokinetics, clinical performance and laboratory examinations were
      extracted from 17 papers of mixed quality on pills containing quinestrol 3 mg and
      norgestrel 12 mg (Quin-Ng) or levonorgestrel 6 mg (Quin-Lng) used by women in
      China. RESULTS: Quin-Lng pills gave steady-state serum levels of ethinylestradiol
      between 0.20-0.25 and 0.15 ng/mL. The 1-year perfect use pregnancy rate was 1.1
      per 100 women-years. Nausea and increased leukorrhea were common; bleeding
      control was good. Hypertension developed in 5.8% of Quin-Ng pill users during the
      first year of use. For Quin-Ng and Quin-Lng once-a-month pills, 1 year
      continuation rates were 73.6 and 82.1 per 100, respectively. CONCLUSIONS: Lack of
      good quality data prevents confident assessment of the safety and efficacy of
      once-a-month pills. Short-term safety information indicates a high incidence of
      bothersome side effects and hypertension. The high monthly estrogen and
      progestogen doses raise questions about the safety of the once-a-month pills.

PMID- 17434015
TI  - The safety of a drospirenone-containing oral contraceptive: final results from
      the European Active Surveillance Study on oral contraceptives based on 142,475
      women-years of observation.
AB  - OBJECTIVES: The study was conducted to compare risks of adverse cardiovascular
      and other events associated with the use of drospirenone (DRSP)-containing oral
      contraceptives (OCs) and other OCs. METHODS AND MATERIALS: The European Active
      Surveillance study (EURAS) was a multinational, prospective, noninterventional
      cohort study of new users of DRSP, levonorgestrel (LNG) and other progestin
      containing OCs. Semiannual follow-up was based on mailed questionnaires, with
      additional follow-up procedures when needed. RESULTS: Overall, 58,674 women were
      followed for 142,475 women-years of observation. Loss to follow-up was 2.4%.
      Serious adverse and fatal events were rare, and rate ratios were close to unity
      (1.0). Cox regression analysis of cardiovascular outcomes yielded hazard ratios
      for DRSP-containing vs. LNG-containing and other OCs of 1.0 and 0.8 (upper 95%
      confidence limits, 1.8 and 1.3) for venous, and 0.3 and 0.3 (upper 95% confidence
      limits, 1.2 and 1.5) for arterial thromboembolism, respectively. CONCLUSIONS:
      Risks of adverse cardiovascular and other serious events in users of a DRSP
      containing OC are similar to those associated with the use of other OCs.

PMID- 17434016
TI  - Contraindications to oral contraceptive use among women in the United States,
      1999-2001.
AB  - OBJECTIVE: The prescription requirement for oral contraceptives (OCs) is designed
      to prevent women with contraindications from using OCs, but this system has never
      been evaluated. This analysis investigates OC use among women who have
      contraindications. METHODS: We use National Health and Nutrition Examination
      Survey data to estimate the prevalence of contraindications among OC users and
      nonusers. We associate OC use with contraindication status, controlling for
      sociodemographic characteristics and access to health services. RESULTS: Overall,
      16% of fecund women aged 20 to 51 years are contraindicated from OC use. The
      prevalence of contraindications among current OC users is 6%, as compared to 19%
      among nonusers. Regression results show that OC use is more strongly associated
      with age, race, marital status and health insurance coverage than with having a
      contraindication to OCs. CONCLUSION: The results suggest that under the
      prescription requirement, screening for contraindications to OCs may be working,
      but not perfectly. More research is needed to identify more effective and
      convenient screening methods.

PMID- 17434017
TI  - Reasons for unprotected intercourse: analysis of the PRAMS survey.
AB  - OBJECTIVES: This study was conducted to identify reasons why women had
      unprotected intercourse that led to an unintended pregnancy. METHODS: As part of
      the Pregnancy Risk Assessment Monitoring System (PRAMS) survey, women with a
      recent unintended viable pregnancy were asked after the birth why they had not
      used birth control. RESULTS: Of 7856 respondents, 33% felt they could not get
      pregnant at the time of conception, 30% did not really mind if they got pregnant,
      22% stated their partner did not want to use contraception, 16% cited side
      effects, 10% felt they or their partner were sterile, 10% cited access problems
      and 18% selected "other." Latent class analysis showed seven patterns of
      response, each identifying strongly with a single reason. CONCLUSIONS: Almost
      half of women with viable unintended pregnancies ending in a birth felt they
      could not/would not get pregnant at the time of conception. Most women identified
      with a single reason for having unprotected intercourse.

PMID- 17434018
TI  - Safety and acceptability with the use of a contraceptive vaginal ring after
      surgical or medical abortion.
AB  - OBJECTIVE: The study was conducted to determine if a contraceptive vaginal ring
      (CVR) is a safe and acceptable method of contraception when used in the proximate
      postabortion period following first-trimester surgical or medical abortion.
      METHODS: A CVR was inserted within 1 week following a medical or surgical
      abortion. Participants were followed up for 3 months to determine safety and
      acceptability. Safety was measured by the absence of signs of infection or
      serious adverse events. Acceptability was assessed by the CVR satisfaction
      survey, completed at the 3-month follow-up visit. RESULTS: Of 81 participants
      enrolled in the study, 69 (85%) completed the first-month follow-up visit, and 54
      (67%) completed the final 3-month follow-up visit. There were no serious adverse
      events and no signs of infection on physical exam. Most adverse events were mild
      and not specifically related to the CVR. Related adverse events were those
      commonly associated with hormonal contraception use. Eighty-nine percent of
      participants chose to continue the CVR as their birth control method. CONCLUSION:
      The CVR is potentially safe and has high acceptability when used in the proximate
      postabortion period following a first-trimester abortion.

PMID- 17434020
TI  - Clinical utility of urine pregnancy assays to determine medical abortion outcome
      is limited.
AB  - BACKGROUND: Determining medical abortion outcome commonly includes a costly
      evaluation such as ultrasonography or serial serum hCG testing. Urine pregnancy
      testing may represent a less costly alternative. METHODS: This prospective
      diagnostic test evaluation study was part of a multisite randomized trial of 1080
      women undergoing medical abortion up to 63 days' gestation who returned 1 and 2
      weeks after receiving mifepristone. Low-sensitivity (LS) and high-sensitivity
      (HS) urine pregnancy tests were performed at each visit, and the results were
      compared to ultrasonography. Sensitivity, specificity, predictive values and
      likelihood ratios of each urine test were determined. RESULTS: In the first week
      following abortion, 14.8% of the LS tests and 7.9% of the HS tests correctly
      predicted outcome. None of the LS tests and only 0.2% of the HS tests were
      falsely negative; however, 85.2% of the LS tests and 91.8% of the HS tests were
      falsely positive. In the second week following abortion, 39.1% of the LS tests
      and 33.8% of the HS tests correctly predicted the medical abortion outcome. Only
      0.2% of the LS tests and 0.3% of the HS were falsely negative; however, 60.8% of
      the LS tests and 65.8% of the HS tests were falsely positive. CONCLUSIONS: Both
      LS and HS urine pregnancy assays reliably assess clinical outcomes of medical
      abortions in cases of negative test results. However, the clinical utility of
      urine assay testing is limited because of the high rate of false-positive
      results.

PMID- 17434019
TI  - Effect of single administration of levonorgestrel on the menstrual cycle.
AB  - BACKGROUND: Levonorgestrel (LNG) 1.5 mg administered within 72 h of unprotected
      coitus is an established method of emergency contraception. Currently, there is
      some, although incomplete, knowledge about the mechanism of action. METHODS: We
      administered 1.5 mg LNG peri-ovulatory to determine the effects on serum
      gonadotrophins, estradiol and progesterone levels. Fourteen women were studied in
      a pretreatment and treatment cycle; eight women (Group A) took LNG 3 days before
      the expected day of ovulation, while 6 (Group B) took LNG a day before the
      expected day of ovulation. RESULTS: The women in Group A had a significant delay
      in their LH peak and onset of the next menses compared with their pretreatment
      cycles (26.4 vs. 39.1 days, p<.05). Those in Group B had no significant changes
      in the endocrine parameters but there was a significant shortening of the mean
      cycle length in comparison with their pretreatment cycles (25.1 vs. 20.2 days).
      CONCLUSION: Levonorgestrel 1.5 mg acts as an emergency contraception by delaying
      the LH surge and interfering with ovulation. It may also disrupt corpus luteum
      formation causing premature luteinization of unruptured follicles.

PMID- 17434021
TI  - Predictors of dual method use for pregnancy and HIV prevention among adolescent
      South African women.
AB  - INTRODUCTION: Dual contraceptive method use is advocated for adolescent women to
      prevent pregnancy, sexually transmitted diseases and HIV. METHODS: We examined
      data from a nationally representative sample of South African women aged 15-24
      years to establish factors associated with dual method use. RESULTS: Only 7% of
      current contraceptive users reported using dual methods, although this percentage
      increased to 28.1% when women reporting hormonal contraception and condom use at
      last sex were included. In multivariate analyses, having talked about condoms
      with a partner was most strongly associated with dual method use (adjusted odds
      ratio (AOR), 12.3; 95% confidence interval (CI), 6.1-25.1) and suggests that
      communication skills might be the most effective way of increasing dual method
      use. Difficulty in accessing condoms was associated with lower odds of dual
      method use (AOR, 0.5; 95% CI, 0.2-1.0). CONCLUSION: We conclude with
      recommendations to increase male involvement and encourage communication between
      partners for the integration of HIV prevention and other reproductive health care
      services.

PMID- 17434022
TI  - Sterilization of male stray dogs with a single intratesticular injection of
      calcium chloride: a dose-dependent study.
AB  - OBJECTIVE: To study a method of chemical sterilization and its efficacy in adult
      male stray dogs. METHODS: Sterilization was performed 45 days after a single
      bilateral intratesticular injection of calcium chloride (CaCl(2)) at the doses of
      5, 10, 15 or 20 mg per testis per kg body weight. RESULTS: Histomorphological
      measures of testes showed total necrosis of testicular tissue at 45 days after an
      injection of either 10 or 15 or 20 mg CaCl(2) along with fibrosis and
      hyalinization in seminiferous tubules and interstitial spaces. Infiltration of
      leucocytes was also observed with the 10- or 15-mg dose. Disintegration of germ
      cell arrangement in seminiferous tubules and washing out of germ cells from the
      tubules were noted with the 5-mg dose. Relative organ weight, epididymal sperm
      count, plasma and intratesticular concentrations of testosterone, testicular
      activities of Delta(5),3beta-hydroxysteroid dehydrogenase (Delta(5),3beta-HSD),
      17beta-hydroxysteroid dehydrogenase (17beta-HSD), glutathione peroxidase (GPx),
      glutathione S-transferase (GST) and superoxide dismutase (SOD) and testicular
      contents of glutathione (GSH) and glutathione disulphide (GSSG) and the ratio of
      GSH/GSSG, all were declined in each of the calcium chloride treated groups in
      comparison to the control group. Increases occurred in testicular malondialdehyde
      (MDA) and plasma concentrations of LH and FSH with each of the treatments by
      comparison with the control group. Plasma concentrations of cortisol, fasting
      blood sugar level, blood urea nitrogen as well as packed cell volume (PCV) and
      total plasma protein were recorded to monitor the changes in chronic stress in
      the experimental animals. Changes in these parameters were not significant.
      CONCLUSION: An intratesticular injection of CaCl(2) at specified doses could be a
      suitable method of sterilization in preference to surgical castration of dogs.

PMID- 17434023
TI  - Postovulatory effects of levonorgestrel in emergency contraception.

PMID- 17434024
TI  - Postovulatory effects of levonorgestrel in emergency contraception (LNG EC).

PMID- 17434026
TI  - Medical Pearl: the evaluation of perioral dermatitis: Use of an extended patch
      test series.

PMID- 17434027
TI  - Surgical Pearl: obtaining a clean histopathologic specimen using a ring curette.

PMID- 17434028
TI  - Medical Pearl: confirming the diagnosis of molluscum contagiosum using 10%
      potassium hydroxide.

PMID- 17434029
TI  - Surgical Pearl: alternate method of loading needle to facilitate subcuticular
      suturing.

PMID- 17434030
TI  - Tanning in body dysmorphic disorder.

PMID- 17434031
TI  - Nephrogenic fibrosing dermopathy with recurrence after allograft failure.

PMID- 17434032
TI  - Schwannoma coexisting with giant congenital melanocytic nevus: is it coincidence?

PMID- 17434033
TI  - Mycosis fungoides involving the nasal mucosa.

PMID- 17434034
TI  - Drug-induced lupus erythematosus in a patient treated with adalumimab.

PMID- 17434035
TI  - Perianal ulceration and other cutaneous ulcerations complicating nicorandil
      therapy.

PMID- 17434036
TI  - Vaginal ulcerations with acute mycoplasma infection.

PMID- 17434037
TI  - Recurrent erythema multiforme in association with recurrent Mycoplasma pneumoniae
      infections.

PMID- 17434038
TI  - Prompt response of refractory Schnitzler syndrome to treatment with anakinra.

PMID- 17434039
TI  - Acquired digital arteriovenous malformation: ultrasound imaging and response to
      long-pulsed neodymium:yttrium-aluminum-garnet treatment.

PMID- 17434040
TI  - Cutaneous vasculitis in two patients taking an herbal supplement containing black
      cohosh.

PMID- 17434041
TI  - Facial edema and crusted patches: a precursor to life-threatening acute systemic
      lupus erythematosus.

PMID- 17434042
TI  - Self-induced paraffinoma in a schizophrenic patient.

PMID- 17434043
TI  - Eruptive latent metastatic melanomas after initiation of antitumor necrosis
      factor therapies.
AB  - We report two cases of late recurrence of eruptive locoregional metastatic
      melanoma occurring 6 and 9 years after definitive surgical treatment. Each case
      (stage IB and IA) occurred after initiation of the subcutaneous anti-tumor
      necrosis factor medications etanercept and adalimumab, respectively. We discuss
      the association of immune suppression and melanoma. These cases illustrate a
      previously unrecognized and potentially causal relationship between tumor
      necrosis factor-alpha inhibition and reactivation of latent melanoma.

PMID- 17434045
TI  - Clinical and molecular dilemmas in the diagnosis of familial epidermolysis
      bullosa pruriginosa.
AB  - Dystrophic epidermolysis bullosa is a rare and clinically heterogeneous
      mechanobullous disorder. One unusual clinical variant is epidermolysis bullosa
      pruriginosa (EBP), in which the combination of pruritus and skin fragility can
      lead to hypertrophic, lichenified nodules and plaques. This form of inherited
      epidermolysis bullosa may not develop clinically until adult life, leading to
      diagnostic confusion with acquired disorders, such as nodular prurigo, lichen
      simplex, lichen planus, hypertrophic scarring, or dermatitis artefacta. As in all
      other forms of dystrophic epidermolysis bullosa, the molecular pathology involves
      mutations in the gene encoding the anchoring fibril protein, type VII collagen
      (COL7A1), but there is no clear genotype-phenotype correlation in EBP. In this
      report, we describe a Chinese-Singaporean family with EBP in whom an autosomal
      dominant glycine substitution mutation, p.G2251E, was identified in exon 86 of
      the COL7A1 gene. This heterozygous mutation was identified in the genomic DNA of
      all 4 affected adults tested, as well as 2 clinically unaffected offspring (aged
      9-29 years). Based on DNA sequencing, we predict that these individuals may
      develop EBP later in life, although additional factors leading to disease
      expression may determine phenotypic expression. Nevertheless, we plan to closely
      monitor these potentially presymptomatic individuals for symptoms of pruritus and
      early signs of the genetic disorder.

PMID- 17434044
TI  - A novel case of IgA paraneoplastic pemphigus associated with chronic lymphocytic
      leukemia.
AB  - Paraneoplastic pemphigus is an autoimmune vesiculobullous and erosive
      mucocutaneous disease associated with an underlying malignancy. Reported
      malignancies include chronic lymphocytic leukemia, non-Hodgkin's lymphoma,
      Castleman's disease, sarcomas, and rarely solid tumors. Patients with
      paraneoplastic pemphigus develop characteristic IgG autoantibodies against
      several antigens including members of the plakin family, bullous pemphigoid
      antigen 1, and desmosomal proteins. IgA pemphigus is another recently
      characterized immunobullous disease that presents as a vesiculopustular eruption
      with neutrophilic infiltration and epidermal acantholysis. Mucous membrane
      involvement is rare. We report what is to our knowledge a unique case with
      features of both IgA pemphigus and paraneoplastic pemphigus associated with
      chronic lymphocytic leukemia.

PMID- 17434046
TI  - Pemphigus vulgaris presenting in a radiation portal.
AB  - We report a case of mucocutaneous pemphigus vulgaris in a patient with squamous
      cell carcinoma of the lung. The cutaneous involvement was limited to the skin
      within his therapeutic radiation portal. The diagnosis of pemphigus vulgaris was
      confirmed by histopathology and immunologic studies. Direct immunofluorescence
      demonstrated IgG and C3 in the intercellular spaces and indirect
      immunofluorescence was positive on monkey esophagus at a titer of 1:160. Enzyme
      linked immunosorbent assay of the patient's serum detected autoantibodies only to
      desmoglein (Dsg)3, with no reactivity to Dsg1. Immunomapping of perilesional skin
      from the irradiated field illustrated decreased Dsg1 expression compared with a
      control sample from an area that was not exposed to radiation. This case provides
      support for the Dsg compensation hypothesis and may also suggest a mechanism by
      which irradiation may induce skin lesions.

PMID- 17434047
TI  - The expanding spectrum of Galli-Galli disease.
AB  - Galli-Galli disease (GGD), a rare genodermatosis in the spectrum of reticulate
      hyperpigmentation, is regarded as an acantholytic variant of Dowling-Degos
      disease. We herein report two patients with GGD exhibiting erythematous scaly
      plaques and lentigo-like macules on the trunk and lower extremities, rather than
      the characteristic reticulate hyperpigmented macules of large body folds.
      Digitate elongations of rete ridges coupled with foci of acantholysis were the
      clues to the diagnosis. A high index of suspicion is needed to diagnose GGD that
      lacks the characteristic reticulate hyperpigmentation of large body folds.

PMID- 17434048
TI  - Lichen planus responding to efalizumab.
AB  - Lichen planus (LP) is a common inflammatory skin disorder of unknown origin. When
      generalized and relapsing, treatment of LP can be a challenge. We present a
      patient with widespread and relapsing generalized LP who was treated with
      efalizumab for 3 months. Both pruritus and the skin lesions responded promptly to
      this biologic. In accordance with the previously reported efficacy in oral
      erosive LP, efalizumab may be a promising novel future treatment option for
      patients with cutaneous LP.

PMID- 17434049
TI  - Bullous pemphigoid positive for anti-BP180 and anti-laminin 5 antibodies in a
      patient with graft-vs-host disease.
AB  - We report the case of a 55-year-old female with bullous pemphigoid (BP) who was
      positive for anti-BP180 and anti-laminin 5 antibodies after development of graft
      vs-host disease (GVHD) caused by a bone marrow transplant. She had tense blisters
      on her trunk and extremities. Histologic examination showed a subepidermal
      blister and marked lymphocytic infiltration, especially eosinophils. Direct
      immunofluorescence revealed a linear deposition of IgG on the base membrane zone.
      Indirect immunofluorescence on 1M NaCl split skin revealed a linear IgG
      deposition to both sides of the epidermal and the dermal layers. Immunoblot
      assays using human epidermal extracts and BP180 NC16a domain recombinant protein
      confirmed the presence of IgG antibodies against BP180 and recombinant BP180
      NC16a domain protein. Furthermore, immunoblotting using laminin 5 purified from
      human keratinocyte extract as the substrate demonstrated reactivity against the
      gamma2 and beta3 subunits but not the alpha3 subunit of laminin 5. We diagnosed
      BP and treated her with prednisolone (40 mg/day). Both skin and oral lesions
      resolved without leaving scars on the bulla. Immune disturbance as well as
      destruction of basal epidermal cells and base membrane by GVHD may result in the
      induction of autoimmune blistering diseases with unusual clinical and laboratory
      manifestations.

PMID- 17434050
TI  - Divided cafe-au-lait macule of the mouth.
AB  - We describe a 4-year-old, otherwise healthy boy with a congenital history of a
      perioral and labial segmental cafe-au-lait macule, who was noted to have
      unilateral localized gingival hyperpigmentation that aligned with the cafe-au
      lait macule. This case is highly illustrative of the embryologic timing of the
      genetic event locally, which leads to cafe-au-lait type hyperpigmentation.
      Because the facial features and the ectoderm overlying the facial muscles develop
      around the third to fourth week of gestation, the distribution of this cafe-au
      lait macule suggests development at the same time.

PMID- 17434051
TI  - Erythrocyte transmembrane electron transfer in haemodialysis patients.
AB  - BACKGROUND AND AIMS: Patients with chronic renal failure, especially those
      treated with haemodialysis, have an increased risk of developing atherosclerotic
      vascular disease probably as a result of enhanced oxidative stress. The human
      cell membrane possesses electron transfer systems which protect against
      extracellular pro-oxidant challenge. We evaluated (1) the erythrocyte velocity of
      ferricyanide reduction (RBC vfcy) in 25 uraemic patients (aged 25-71 years; 14
      males), (2) the changes induced by a single haemodialysis session and (3)
      biomarkers of oxidative stress. METHODS AND RESULTS: Before and after a mid-week
      dialysis session, we measured RBC vfcy, erythrocyte glutathione (RBC GSH), plasma
      and red cell membrane malondialdehyde (P and RBC MDA), plasma sulphydryl groups
      (P SH), plasma vitamin C levels and haemolysis percentage. Pre-dialysis RBC GSH
      (0.68+/-0.13 vs 0.80+/-0.13 mg/mL, p<0.01), P SH (266+/-74 vs 406+/-78
      micromol/L, p<0.01) and plasma vitamin C (7.0+/-5.1 vs 21.5+/-8.5mg/L, p<0.001)
      were lower than in 25 age-sex-matched healthy controls; P MDA (1.57+/-0.52 vs
      0.54+/-0.29 nmol/mL, p<0.001), RBC MDA (0.42+/-0.13 vs 0.34+/-0.16 nmol/mL,
      p<0.05) and haemolysis (1.2+/-0.3 vs 0.7+/-0.3%, p<0.001) were increased.
      Baseline RBC vfcy did not differ from normals (13.1+/-5.2 vs 12.9+/-3.2
      mmol/mL/h). Following dialysis, RBC vfcy (to 8.9+/-4.5 mmol/mL/h, p<0.001)
      decreased, as well as P MDA, RBC MDA and plasma vitamin C (to 2.5+/-1.4 mg/L,
      p<0.001), whereas P SH groups increased (to 413+/-99 micromol/L, p<0.001);
      haemolysis percentage remained high. RBC vfcy values were correlated to RBC GSH
      and vitamin C levels. CONCLUSIONS: Uraemic patients showed signs of oxidative
      stress. Pre-dialysis RBC vfcy is maintained in the normal range on account of a
      reduced intracellular content of GSH and in spite of low plasma ascorbate. A
      single haemodialysis treatment reduced biomarkers of protein and lipid oxidation
      but markedly impaired transmembrane electron transfer, which could be explained
      by acute depletion of electron donors.

PMID- 17434052
TI  - Proinflammatory cytokines and cardiac abnormalities in uncomplicated obesity:
      relationship with abdominal fat deposition.
AB  - BACKGROUND AND AIM: Obesity can be considered a state of chronic, low-grade
      inflammation. Particularly, visceral adipose tissue (VAT) seems to be an active
      compartment in pro-inflammatory molecule secretion. The possible existence of a
      correlation between circulating cytokines, their soluble receptors, abdominal fat
      accumulation and echocardiographic abnormalities in uncomplicated obesity was
      investigated. METHODS AND RESULTS: Echocardiographic parameters, C-reactive
      protein (CRP), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6-R), tumor
      necrosis factor-alpha (TNF-alpha) and soluble TNF receptor I (TNFR-I) were
      assessed in 27 normotensive obese women (age 33.3+/-8.3 years; BMI 43.5+/-4.8
      kg/m2) and 15 normal-weight controls (age 36.8+/-8.2 years; BMI 22.6+/-1.7
      kg/m2). VAT was assessed by CT. The obese patients had higher serum IL-6
      (p<0.01), sIL-6-R (p<0.0001), sIL-6-R/IL-6 complex (p<0.05), TNF-alpha (p<0.02),
      sTNF-alpha-RI (p<0.03) and CRP (p<0.0001) levels than normal women. Moreover, end
      diastolic septum thickness (SW), end-diastolic posterior wall thickness (PW),
      absolute and indexed left ventricular mass, deceleration time (DT), myocardial
      performance index (MPI) and isovolumetric relaxation time (IVRT) were correlated
      with sIL-6-R, sIL-6-R/IL-6 complex and CRP levels. Interestingly, sIL-6-R, sIL-6
      R/IL-6 complex, CRP, SW, PW, DT and MPI were higher in patients with a VAT area
      >130 cm2 than those with <130 cm2. CONCLUSION: In normotensive obese women
      several pro-inflammatory molecules correlate with both echocardiographic
      abnormalities and the amount of intra-abdominal fat; these results may support a
      role for visceral fat in predisposing to cardiac dysfunction, possibly through a
      low-grade state of inflammation.

PMID- 17434053
TI  - Effects of birth weight on spontaneous baroreflex sensitivity in adult life.
AB  - BACKGROUND AND AIM: Several epidemiological studies have suggested a link between
      low birth weight and coronary heart disease; this may be partly due to the
      association between low birth weight and conventional risk factors. Among the
      factors involved in the regulation of cardiovascular homeostasis, baroreflexes
      play a crucial role. The objective of the present study was to investigate if
      baroreflex sensitivity (BRS) in adulthood is associated with birth weight.
      METHODS AND RESULTS: Two hundred and eleven adults from Turin, Italy, aged 22-24
      years, were examined in a cross sectional survey. Birth weight, blood pressure,
      pulse rate, family history of hypertension, anthropometric and environmental
      parameters and spontaneous baroreflex sensitivity were evaluated. In this study
      we observed a significant increase in baroreflex sensitivity across the tertiles
      of birth weight, even after correction for gender, blood pressure and heart rate;
      in a regression model, birth weight was positively and independently associated
      with BRS; moreover, BRS showed a significant negative correlation with adult
      pulse rate. CONCLUSION: This finding may be helpful in understanding the
      association between low birth weight and cardiovascular disease outcome in later
      life, since baroreflex failure is associated with an increased cardiovascular
      morbidity and mortality.

PMID- 17434054
TI  - Comparison of methods to identify individuals at increased risk of cardiovascular
      disease in Italian cohorts.
AB  - BACKGROUND AND AIMS: Guidelines for the primary prevention of cardiovascular
      disease recommend the use of risk-assessment methods to identify high risk
      patients who can benefit from lifestyle changes and/or drug treatment. Although
      all these risk-prediction methods are based on the same principle, they produce
      different risk estimates. The aim of this study was to compare the most recent
      and widely used cardiovascular risk-prediction methods and the respective
      guidelines when applied to Italian cohorts. METHODS AND RESULTS: Seven different
      risk-assessment methods were applied to two groups of subjects, 536 healthy
      individuals and 426 diabetic patients. Sensitivity and specificity of Framingham
      based risk-assessment methods were calculated using the Framingham full equation
      as the reference standard. The extent of concordance among the different risk
      assessment methods was determined by kappa test. By using NCEP-ATPIII risk
      calculator, modified Sheffield tables, Joint European Societies charts, Joint
      British Societies charts, Italian CUORE Project charts, European SCORE charts and
      New Zealand National Heart Foundation charts in the group of 536 healthy
      subjects, lipid-lowering treatment would be recommended in 17.5%, 12.7%, 12.1%,
      8.6%, 5.0%, 4.7%, and 1.1% subjects, respectively. By using the same risk
      assessment methods in the group of 426 diabetic patients, treatment would be
      recommended for 100%, 82.9%, 66.9%, 77.7%, 43.0%, 74.9%, and 47.4% patients,
      respectively. The Joint British charts and the modified Sheffield tables showed
      the closest agreement with the reference standard. CONCLUSIONS: Our study
      confirms that the use of different risk-assessment methods in clinical practice
      can substantially change risk estimation and consequently statin prescription
      rate. The Framingham-based risk-assessment methods and particularly the NCEP
      ATPIII guidelines select for lipid-lowering treatment a higher number of subjects
      than those identified according to European and Italian recommendations.

PMID- 17434056
TI  - Surgical anatomy of the maxillary region.

PMID- 17434057
TI  - Reconstruction of maxillary defects with the radial forearm free flap.

PMID- 17434058
TI  - The fibula free flap in maxillary reconstruction.

PMID- 17434059
TI  - Buccal fat pad in maxillary reconstruction.

PMID- 17434060
TI  - Temporalis system in maxillary reconstruction: temporalis muscle and
      temporoparietal galea flaps.

PMID- 17434061
TI  - Maxillary reconstruction using zygomaticus implants.

PMID- 17434062
TI  - Maxillofacial prosthetic management of the maxillary resection patient.

PMID- 17434063
TI  - Mammographic pattern analysis: an emerging risk assessment tool.

PMID- 17434064
TI  - Fractal analysis of mammographic parenchymal patterns in breast cancer risk
      assessment.
AB  - RATIONALE AND OBJECTIVES: To evaluate fractal-based computerized image analyses
      of mammographic parenchymal patterns in the task of differentiating between women
      at high risk and women at low risk for developing breast cancer. MATERIALS AND
      METHODS: The fractal-based texture analyses are based on a box-counting method
      and a Minkowski dimension, and were performed within the parenchymal regions of
      normal mammograms. Four approaches were evaluated: 1) a conventional box-counting
      method, 2) a modified box-counting technique using linear discriminant analysis
      (LDA), 3) a global Minkowski dimension, and 4) a modified Minkowski technique
      using LDA. These fractal based texture features were extracted from regions of
      interest to assess the mammographic parenchymal patterns of the images. Receiver
      operating characteristic analysis was used to evaluate the performance of these
      features in the task of differentiating between the two groups of women. RESULTS:
      Receiver operating characteristic analysis yielded an A(z) value of 0.74 based on
      the conventional box-counting technique and an A(z) value of 0.84 based on the
      global Minkowski dimension in the task of distinguishing between the two groups.
      By using LDA to assess the characteristics of mammograms, A(z) values of 0.90 and
      0.93 were obtained in differentiating the two groups, for the modified box
      counting and Minkowski techniques, respectively. Statistically significant
      improvement was achieved (P < .05) with the new techniques compared to the
      conventional fractal analysis methods. A simulation study, which used the slope
      and intercept extracted from the least square fit of the experimental data with
      the LDA approaches, yielded A(z) values similar to those obtained with the
      conventional approaches in the task of differentiating between the two groups.
      CONCLUSIONS: The proposed LDA approach improved significantly the separation
      between the two groups based on experimental data. Because this approach was used
      as a linear classifier rather than as a regression function, it combined the
      fractal analysis with the knowledge of the high- and low-risk patterns, and thus
      better characterized the multifractal nature of the parenchymal patterns. We
      believe that the proposed analyses based on the LDA technique to characterize
      mammographic parenchymal patterns may potentially yield radiographic markers for
      assessing breast cancer risk.

PMID- 17434065
TI  - Tissue Doppler and strain imaging for evaluating tissue elasticity of breast
      lesions.
AB  - RATIONALE AND OBJECTIVES: Sonoelastography depicts the intrinsic elastic
      properties of a tissue which are characterized by the strain applied to achieve
      tissue deformation and the velocity at which tissue deformation occurs. The
      present study served to investigate whether the specificity of B-mode ultrasound
      (US) can be improved by combining B-mode imaging with tissue Doppler imaging
      (TDI) and offline analysis of tissue strain imaging (TSI). MATERIALS AND METHODS:
      Fifty women, 25 with malignant and 25 with benign focal breast lesions, were
      examined by US with a linear transducer (9 MHz, Aplio, Toshiba, Otawara, Japan).
      B-mode US views of the lesions were overlaid with color-coded TDI information and
      area quotients (AQ = area B-mode view/area TDI) were calculated. TSI views were
      reconstructed offline from the source data. This was done by placing a region of
      interest (ROI) in the target lesion and color-encoded display of the information.
      In addition, tissue elasticity was evaluated using a scale of 1-5 corresponding
      to the BI-RADS categories. Maximum strain (strain factor, SF) was determined in
      the ROI. All patients also underwent mammography. Sensitivities and specificities
      were calculated and statistical analysis was performed using Wilcoxon's test.
      RESULTS: Sensitivity/specificity was 96%/68% for B-mode US, 100%/40% for combined
      B-mode US and mammography, and 96%/80% for TSI. The AQ of benign and malignant
      lesions was significantly different (p = .00008) as was the difference in SF (p =
      .0004). The readers considered TSI a feasible technique. CONCLUSION: Evaluation
      of elasticity based on the quantification of strain factors improves
      characterization of focal breast lesions, especially the differentiation of BI
      RADS 3 and 4 lesions. Surprisingly, significant results in characterizing breast
      lesions were obtained with the simple technique of TDI, showing a lower tissue
      displacement in malignant cases.

PMID- 17434066
TI  - Computer-aided mass detection based on ipsilateral multiview mammograms.
AB  - RATIONALE AND OBJECTIVES: Recent reports on advances in computer-aided detection
      (CAD) indicate that current schemes miss early-stage breast cancers and result in
      a relatively large false-positive detection rate in order to achieve a high
      sensitivity rate for mass detection. This paper is inspired by the interpretation
      procedure from mammographers. The abnormal diagnosis can be derived from multiple
      views but is not available through single-view image analysis. MATERIALS AND
      METHODS: A new multiview CAD system for early-stage breast cancer detection,
      which is based on modifying the optimized CAD algorithms from our prior single
      view CAD system for constructing an adaptive ipsilateral multiview concurrent CAD
      system, is presented in this paper. The selection and design for the training and
      testing ipsilateral multiview mammogram databases are described here. RESULTS:
      The performance evaluation of the developed ipsilateral multiview CAD system
      using free-response receiver operating characteristic analysis and computerized
      receiver operating characteristic experiments are presented. The results
      indicated that the proposed multiview CAD system is significantly superior to the
      single-view CAD systems based on statistically standard P-values. CONCLUSION:
      This paper addresses a very important and timely project. It is related to two
      main problems regarding the development of breast cancer detection and diagnosis:
      early-stage detection and diagnosis of breast cancer with digital mammogram, and
      overall improvement of CAD system performance for clinical implementation. In
      order to improve the efficacy, accuracy, and efficiency of the current CAD
      scheme, an entirely new class of CAD method is required. This paper is unique in
      that a comprehensive and state-of-the-art approach is proposed for the CAD scheme
      of digital mammography. From the design aspect of the CAD scheme, the proposed
      ipsilateral multiview CAD method is innovative and quite different from current
      single-view CAD methods.

PMID- 17434067
TI  - Digital mammography: comparative performance of color LCD and monochrome CRT
      displays.
AB  - RATIONALE AND OBJECTIVES: To evaluate the comparative performance of high
      fidelity liquid crystal display (LCD) and cathode ray tube (CRT) devices for
      mammography applications, and to assess the impact of LCD viewing angle on
      detection accuracy. MATERIALS AND METHODS: Ninety 1 k x 1 k images were selected
      from a database of digital mammograms: 30 without any abnormality present, 30
      with subtle masses, and 30 with subtle microcalcifications. The images were used
      with waived informed consent, Health Insurance Portability and Accountability Act
      compliance, and Institutional Review Board approval. With postprocessing
      presentation identical to those of the commercial mammography system used, 1 k x
      1 k sections of images were viewed on a monochrome CRT and a color LCD in native
      grayscale, and with a grayscale representative of images viewed from a 30 degrees
      or 50 degrees off-normal viewing angle. Randomized images were independently
      scored by four experienced breast radiologists for the presence of lesions using
      a 0-100 grading scale. To compare diagnostic performance of the display modes,
      observer scores were analyzed using receiver operating characteristic (ROC) and
      analysis of variance. RESULTS: For masses and microcalcifications, the detection
      rate in terms of the area under the ROC curve (A(z)) showed a 2% increase and a
      4% decrease from CRT to LCD, respectively. However, differences were not
      statistically significant (P > .05). The viewing angle data showed better
      microcalcification detection but lower mass detection at 30 degrees viewing
      orientation. The overall results varied notably from observer to observer
      yielding no statistically discernible trends across all observers, suggesting
      that within the 0-50 degrees viewing angle range and in a controlled observer
      experiment, the variation in the contrast response of the LCD has little or no
      impact on the detection of mammographic lesions. CONCLUSIONS: Although CRTs and
      LCDs differ in terms of angular response, resolution, noise, and color, these
      characteristics seem to have little influence on the detection of mammographic
      lesions. The results suggest comparable performance in clinical applications of
      the two devices.

PMID- 17434068
TI  - Perfusion CT of breast carcinoma: arterial perfusion of nonscirrhous carcinoma
      was higher than that of scirrhous carcinoma.
AB  - RATIONALE AND OBJECTIVES: Our goals were to apply perfusion CT technique to
      breast tumor and to evaluate the correlation between arterial perfusion value and
      other tumor characteristics. MATERIALS AND METHODS: Thirty-one female patients
      with primary breast tumors were included in this study. A single-slice dynamic CT
      was performed after an intravenous bolus injection of contrast material (40 ml;
      370 mg I/ml) at 8 ml/sec. The parameters were calculated on a pixel-by-pixel
      basis by using maximum slope method, and quantitative maps of arterial perfusion
      were created. Statistical correlation between tumor size, patient age, and
      perfusion were assessed. Differences in perfusion between scirrhous and
      nonscirrhous carcinoma were also assessed. RESULTS: Perfusion CT images were
      successfully created for 24 patients (mean age, 55.9 years old; range, 36-85
      years). In five patients, dynamic CT was not performed due to lack of
      visualization of the breast tumor on unenhanced CT. In two patients, reliable
      perfusion CT image could not be created because of motion artifact. The mean
      perfusion for 24 tumors was 33.1 +/- 16.9 ml/min/100 ml (mean +/- SD; range, 14
      78), and the tumor perfusion did not correlate with patient's age or tumor size
      (21.0 +/- 10.2 mm; range, 10-45 mm). The mean perfusion of nonscirrhous carcinoma
      (45.8 ml/min/100 ml; n = 11) was higher than that of scirrhous carcinoma (22.7
      ml/min/100 ml; n = 11; P < .001). CONCLUSION: Determination of the perfusion of
      breast carcinoma is feasible by dynamic CT and can be performed during a routine
      CT study without much supplementary burden on the patient. There are differences
      in blood flow between scirrhous and nonscirrhous breast carcinoma, and further
      research is needed to determine the impact of this finding.

PMID- 17434069
TI  - Comparison of three methods to increase knowledge about breast cancer and breast
      cancer screening in screening mammography patients.
AB  - RATIONALE AND OBJECTIVES: The specific aim of the study was to determine which of
      several cost-effective interventions is best able to improve the breast cancer
      knowledge of women who present for screening mammography. MATERIALS AND METHODS:
      A total of 198 English-speaking women, with no personal or family history of
      breast cancer, were recruited and randomized to four groups when they presented
      to the clinic for a screening mammogram. All women filled in a demographic data
      form and answered a questionnaire containing nine questions about breast cancer,
      risk, and screening to assess their knowledge and perception. Three educational
      interventions were tested in this study. The first consisted of a brochure, which
      provided answers to the questionnaire items and addressed the issues in more
      depth. The second intervention was an educational conversation with a specially
      trained mammography technologist. She reviewed the subject's answers to the
      questionnaire items correcting and/or clarifying them. The third intervention
      consisted of the brochure together with the conversation with a trained
      technologist. There was also a control group that just filled in the study
      questionnaire but did not receive an educational intervention. The same
      questionnaire was administered by telephone 4 to 6 weeks after the screening
      experience to all study subjects. Changes in their knowledge and perceptions of
      breast cancer were measured and compared. RESULTS: A statistically significant
      increase in knowledge was found in all of the three investigated groups compared
      to the control group. There were no statistically significant differences in the
      amount of increase between women who underwent different interventions.
      CONCLUSIONS: All three interventions resulted in increased knowledge about breast
      cancer and screening. No differences in the amount of knowledge increase were
      found between three interventions tested. The educational brochure seems to
      represent the most convenient and least costly method to increase knowledge about
      breast cancer and screening among women who present for screening mammography.

PMID- 17434070
TI  - Monitoring breast cancer response to neoadjuvant systemic chemotherapy using
      parametric contrast-enhanced MRI: a pilot study.
AB  - RATIONALE AND OBJECTIVES: Neoadjuvant systemic therapy (NST) is the standard
      treatment for locally advanced breast cancer and a common option for primary
      operable disease. It is important to develop standardized imaging techniques that
      can monitor and quantify response to NST enabling treatment tailored to each
      individual patient, and facilitating surgical planning. Here we present a high
      spatial resolution, parametric method based on dynamic contrast-enhanced (DCE)
      magnetic resonance imaging (MRI), which evaluates breast cancer response to NST.
      MATERIALS AND METHODS: DCE-MRI examinations were performed twice on 17 breast
      cancer patients, before and after treatment. Seven sets of axial breast images
      were sequentially recorded at 1.5 Tesla applying a three-dimensional, gradient
      echo at a spatial resolution approximately 2 x 1.2 x 0.6 mm(3) and temporal
      resolution approximately 2 minutes, using gadopentate dimeglumine (0.1 mmol/kg
      wt). Image analysis was based on a color-coded scheme related to physiologic
      perfusion parameters. RESULTS: A high Pearson correlation coefficient of 0.96 (P
      < .0001) was found between the histopathologic estimation of viable neoplastic
      tissue volume and the segmented volume of all the pixels demonstrating fast and
      steady state washout after NST (colored in light red and green). Segmentation of
      these pixels before and after NST indicated response in terms of reduced tumor
      volume and a parallel decrease in enhancement rate which reflects diminished
      transcapillary transfer of the contrast agent. CONCLUSIONS: The use of a
      parametric MRI technique provided a means to standardize segmentation and
      quantify changes in the perfusion of breast neoplastic tissue in response to NST.
      Whether this technique can serve to predict breast cancer recurrence and survival
      rates requires further clinical testing.

PMID- 17434071
TI  - Injection rate threshold of triple-lumen central venous catheters: an in vitro
      study.
AB  - RATIONALE AND OBJECTIVES: Computed tomographic angiography (CTA) requires the
      rapid injection of contrast media ideally through an 18-gauge intravenous line in
      the antecubital fossa. Patients with CVCs undergoing CTA, however, are typically
      injected at low rates for two reasons: the potential for catheter failure and
      because of the lack of manufacturer recommendations for high injection rates
      typically used during CTA. The purpose of the study is to measure the injection
      rate thresholds of CVC. The results suggest that CVC can be used at high
      injection rates that are now typically used with peripheral intravenous catheters
      during CTA. MATERIALS AND METHODS: We used 16-cm-long catheters and 20-cm-long
      catheters in six groups (n = 5 for each catheter length). After the catheters
      were placed into a water bath, each group was injected at 5, 10, 15, 20, 25, and
      30 ml/sec. New contrast, pressure tubing, and catheters were used for each test.
      RESULTS: No catheter ruptures were encountered during the experiment, but there
      was one episode of power injector tubing rupture during the injection of a 16-cm
      catheter at an injection rate of 30 ml/sec. CONCLUSION: No catheter failures were
      demonstrated in this study using injection rates well above those used in
      conventional CTA. Power injector tubing failure was demonstrated at an injection
      rate of 30 ml/sec, which generated mean pressures in the 16-cm catheters of 920
      psi (tubing rating per manufacturer is 300 psi). This study demonstrated no
      catheter or injector tubing failure at injection rates of 5 to 25 ml/sec.

PMID- 17434072
TI  - Automated detection of small pulmonary nodules in whole lung CT scans.
AB  - RATIONALE AND OBJECTIVES: The objective of this work was to develop and evaluate
      a robust algorithm that automatically detects small solid pulmonary nodules in
      whole lung helical CT scans from a lung cancer screening study. MATERIALS AND
      METHODS: We developed a three-stage detection algorithm for both isolated and
      attached nodules. The algorithm consisted of nodule search space demarcation,
      nodule candidates' generation, and a sequential elimination of false positives.
      Isolated nodules are nodules that are surrounded by lung parenchyma, whereas
      attached nodules are connected to large, dense structures such as pleural and/or
      mediastinal surface. Two large well-documented whole lung CT scan databases
      (Databases A and B) were created to train and test the detection algorithm.
      Database A contains 250 sequentially selected scans with 2.5-mm slice thickness
      that were obtained at Weill Medical College of Cornell University. With equipment
      upgrade at this college, a second database, Database B, was created containing
      250 scans with a 1.25-mm slice thickness. A total of 395 and 482 nodules were
      identified in Databases A and B, respectively. In both databases, the majority of
      the nodules were isolated, comprising 72.1% and 82.3% of nodules in Databases A
      and B, respectively. RESULTS: The detection algorithm was trained and tested on
      both Databases A and B. For isolated nodules with sizes 4 mm or larger, the
      algorithm achieved 94.0% sensitivity and 7.1 false positives per case (FPPC) for
      Database A (2.5 mm). Similarly, the algorithm achieved 91% sensitivity and 6.9
      FPPC for Database B (1.25 mm). The algorithm achieved 92% sensitivity with 17.4
      FPPC and 89% sensitivity with 5.5 FFPC for attached nodules with sizes 3 mm or
      larger in the Database A (2.5 mm) and Database B (1.25 mm), respectively.
      CONCLUSION: The developed algorithm achieved practical performance for automated
      detection of both isolated and the more challenging attached nodules. The
      automated system will be a useful tool to assist radiologists in identifying
      nodules from whole lung CT scans in a clinical setting.

PMID- 17434073
TI  - Computer-aided joint space analysis (CAJSA) of the proximal-interphalangeal joint
      normative age-related and gender specific data.
AB  - RATIONALE AND OBJECTIVES: To provide reference data for computer-aided joint
      space analysis (CAJSA) based on a semiautomated and computer-aided diagnostic
      system for the measurement of joint space widths (ie, proximal-interphalangeal
      joint), considering gender-specific and age-related differences. MATERIALS AND
      METHODS: A total of 869 subjects were enrolled (351 females/518 males) with
      radiographs of the hand. All participants underwent measurements of joint space
      distances at the proximal-interphalangeal articulation (JSD-PIP) of the second to
      fifth finger using CAJSA technology. RESULTS: The data verify a notable age
      related decrease of CAJSA parameters, showing an accentuated age-related joint
      space narrowing in women. Additionally, males showed a significant wider JSD-PIP
      (+15.4%) compared with the female cohort for all age groups. CONCLUSIONS: Our
      data present gender-specific and age-related normative reference values for
      computer-aided joint space analysis of JSD-PIP and provide a valid and reliable
      quantification of disease-related joint space narrowing, particularly in patients
      with osteoarthritis and rheumatoid arthritis involving the peripheral small hand
      joints.

PMID- 17434074
TI  - Enrollment in a brain magnetic resonance study: results from the Women's Health
      Initiative Memory Study Magnetic Resonance Imaging Study (WHIMS-MRI).
AB  - RATIONALE AND OBJECTIVES: The rates of enrollment of volunteers for brain
      magnetic resonance imaging (MRI) studies vary by demographic and clinical
      characteristics. We use data from a large MRI study to identify factors
      associated with differential enrollment and to examine potential biases this may
      produce in study results. MATERIALS AND METHODS: Results from recruitment of
      1,431 women into the MRI substudy of the Women's Health Initiative Memory Study
      (WHIMS-MRI) are described. A sensitivity analysis was conducted to estimate the
      degree of bias associated with missing data on estimates of risk factor
      relationships. RESULTS: Of 2,345 women contacted from an established cohort of
      women older than 70 years of age, 72% consented to undergo screening for WHIMS
      MRI. Scanning was ultimately completed on 61%. Completion rates varied according
      to a range of sociodemographic, lifestyle, and clinical characteristics that may
      be related to study outcomes. Plausible levels of selective enrollment in
      magnetic resonance imaging studies may produce moderate biases (< +/-20%) in
      characterizations of risk factor relationships. Adverse events, such as
      claustrophobia, occurred during 1.7% of the attempted scans and, in 0.8% of
      instances, led to lost data. CONCLUSIONS: Enrollment of older women into brain
      imaging studies is feasible, although selection biases may limit how well study
      cohorts reflect more general populations.

PMID- 17434075
TI  - Image quality of the aortic and mitral valve with CT: relative versus absolute
      delay reconstruction.
AB  - RATIONALE AND OBJECTIVE: The purpose of this study was to compare image quality
      and artifacts of 16-detector row CT imaging of the aortic and mitral valve when
      performing ECG-gated synchronization using relative and absolute reconstructions.
      MATERIALS AND METHODS: Cardiac CT was performed in 22 consecutive patients; 20
      data sets per RR interval were reconstructed with relative and absolute
      reconstructions. Mean and variability of heart rate during data acquisition were
      noted. Two readers assessed contrast media-related artifacts, calcification
      related artifacts, ECG gating-related artifacts, and image quality in parallel
      and perpendicular planes. RESULTS: Contrast media-related and calcification
      related artifacts similarly occurred with both reconstruction techniques. ECG
      gating-related artifacts occurred in both valves more often with relative
      reconstructions than with absolute reconstructions (p = .001). Image quality was
      significantly better for absolute reconstructions for the open aortic cusp
      surface (p = .014) and edge (p = .008) in both planes, and of the closed mitral
      valve leaflets (p = .003) and apposition zone (p = .003) in perpendicular planes.
      Occurrence of ECG gating-related artifacts in both valves significantly
      correlated (p = .01) with heart rate variability for relative reconstructions,
      whereas no correlation was found using the absolute technique. CONCLUSION:
      Absolute reconstructions allow CT imaging of the aortic and mitral valve with
      fewer artifacts and are less sensitive to heart rate variability as compared to
      relative reconstructions.

PMID- 17434076
TI  - Academic radiology and the emergency department: does it need changing?
AB  - RATIONAL AND OBJECTIVES: The increasing importance of imaging for both diagnosis
      and management in patient care has resulted in a demand for radiology services 7
      days a week, 24 hours a day, especially in the emergency department (ED). We
      hypothesized the resident preliminary reports were better than generalist
      radiology interpretations, although inferior to subspecialty interpretations.
      MATERIALS AND METHODS: Total radiology volume through our Level I pediatric and
      adult academic trauma ED was obtained from the radiology information system. We
      conducted a literature search for error and discordant rates between radiologists
      of varying experience. For a 2-week prospective period, all preliminary reports
      generated by the residents and final interpretations were collected. Significant
      changes in the report were tabulated. RESULTS: The ED requested 72,886 imaging
      studies in 2004 (16% of the total radiology department volume). In a 2-week
      period, 12 of 1929 (0.6%) preliminary reports by residents were discordant to the
      final subspecialty dictation. In the 15 peer-reviewed publications documenting
      error rates in radiology, the error rate between American Board of Radiology
      (ABR)-certified radiologists is greater than that between residents and
      subspecialists in the literature and in our study. However, the perceived error
      rate by clinicians outside radiology is significantly higher. CONCLUSION: Sixteen
      percent of the volume of imaging studies comes through the ED. The residents
      handle off-hours cases with a radiology-detected error rate below the error rate
      between ABR-certified radiologists. To decrease the perceived clinician
      identified error rate, we need to change how academic radiology handles ED cases.

PMID- 17434077
TI  - The American Board of Radiology perspective on maintenance of certification: Part
      IV--practice quality improvement in diagnostic radiology.

PMID- 17434078
TI  - Healing elixir.

PMID- 17434081
TI  - NIH funding restricts neurological research.

PMID- 17434079
TI  - Electronically intuitive---not me.

PMID- 17434082
TI  - Glucose and the ischaemic brain: too much of a good thing?

PMID- 17434083
TI  - Heparin for acute ischaemic stroke: a never-ending story?

PMID- 17434084
TI  - In search of genes for stroke.

PMID- 17434085
TI  - Pathological gambling in Parkinson's disease.

PMID- 17434086
TI  - One WHO STEPS Stroke tool for all settings?

PMID- 17434087
TI  - Improving WHO STEPS Stroke in Brazil.

PMID- 17434090
TI  - Let's talk about brains: International Brain Awareness Week.

PMID- 17434091
TI  - John Hardy: which disease will he solve next?

PMID- 17434093
TI  - Hindsight is a wonderful thing.

PMID- 17434094
TI  - Glucose-potassium-insulin infusions in the management of post-stroke
      hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK).
AB  - BACKGROUND: Hyperglycaemia after acute stroke is a common finding that has been
      associated with an increased risk of death. We sought to determine whether
      treatment with glucose-potassium-insulin (GKI) infusions to maintain euglycaemia
      immediately after the acute event reduces death at 90 days. METHODS: Patients
      presenting within 24 h of stroke onset and with admission plasma glucose
      concentration between 6.0-17.0 mmol/L were randomly assigned to receive variable
      dose-insulin GKI (intervention) or saline (control) as a continuous intravenous
      infusion for 24 h. The purpose of GKI infusion was to maintain capillary glucose
      at 4-7 mmol/L, with no glucose intervention in the control group. The primary
      outcome was death at 90 days, and the secondary endpoint was avoidance of death
      or severe disability at 90 days. Additional planned analyses were done to
      determine any differences in residual disability or neurological and functional
      recovery. The trial was powered to detect a mortality difference of 6% (sample
      size 2355), with 83% power, at the 5% two-sided significance level. This study is
      registered as an International Standard Randomised Controlled Trial (number
      ISRCTN 31118803) FINDINGS: The trial was stopped due to slow enrolment after 933
      patients were recruited. For the intention-to-treat data, there was no
      significant reduction in mortality at 90 days (GKI vs control: odds ratio 1.14,
      95% CI 0.86-1.51, p=0.37). There were no significant differences for secondary
      outcomes. In the GKI group, overall mean plasma glucose and mean systolic blood
      pressure were significantly lower than in the control group (mean difference in
      glucose 0.57 mmol/L, p<0.001; mean difference in blood pressure 9.0 mmHg,
      p<0.0001). INTERPRETATION: GKI infusions significantly reduced plasma glucose
      concentrations and blood pressure. Treatment within the trial protocol was not
      associated with significant clinical benefit, although the study was underpowered
      and alternative results cannot be excluded.

PMID- 17434095
TI  - Low-molecular-weight heparin compared with aspirin for the treatment of acute
      ischaemic stroke in Asian patients with large artery occlusive disease: a
      randomised study.
AB  - BACKGROUND: Acute stroke patients with large artery occlusive disease (LAOD) have
      a distinct pathophysiology and may respond differently to anticoagulation
      treatments. We compared the efficacy of a low-molecular-weight heparin (LMWH),
      nadroparin calcium, with aspirin in Asian acute stroke patients with LAOD.
      METHODS: Acute ischaemic stroke patients with onset of symptoms less than 48 h
      and LAOD (diagnosed by transcranial doppler imaging, carotid duplex scan, or
      magnetic resonance angiography) were recruited. Patients were randomly assigned
      to receive either subcutaneous nadroparin calcium 3800 anti-factor Xa IU/0.4 mL
      twice daily or oral aspirin 160 mg daily for 10 days, and then all received
      aspirin 80-300 mg once daily for 6 months. This study is registered at
      www.strokecenter.org/trials (number 493). FINDINGS: Among 603 patients recruited,
      353 (180 LMWH, 173 aspirin) had LAOD (300 had intracranial LAOD only, 42 had both
      intracranial and extracranial disease, and 11 had extracranial disease only). The
      proportion of patients with good outcomes at 6 months (Barthel index >or=85) was
      73% in the LMWH group and 69% in the aspirin group (absolute risk reduction 4%;
      95% CI -5 to 13). Analysis of prespecified secondary outcome measures showed a
      benefit in outcome for LMWH versus aspirin on the modified Rankin scale
      dichotomised at 0-1 (odds ratio 1.55, 95% CI 1.02-2.35). Haemorrhagic
      transformation of infarct and severe adverse events were similar in both groups.
      Post-hoc analyses of patients without LAOD, and all treated patients, showed
      similar proportions with a good outcome in aspirin and LMWH groups (78%vs 79% and
      73%vs 75%, respectively). INTERPRETATION: Overall, the results do not support a
      significant benefit of LMWH over aspirin in patients with LAOD. The benefits
      indicated in most outcome measures warrant further investigation into the use of
      anticoagulation for acute stroke in patients with large artery atherosclerosis,
      particularly in intracranial atherosclerosis.

PMID- 17434096
TI  - A genome-wide genotyping study in patients with ischaemic stroke: initial
      analysis and data release.
AB  - BACKGROUND: Despite evidence of a genetic role in stroke, the identification of
      common genetic risk factors for this devastating disorder remains problematic. We
      aimed to identify any common genetic variability exerting a moderate to large
      effect on risk of ischaemic stroke, and to generate publicly available genome
      wide genotype data to facilitate others doing the same. METHODS: We applied a
      genome-wide high-density single-nucleotide-polymorphism (SNP) genotyping approach
      to a cohort of samples with and without ischaemic stroke (n=278 and 275,
      respectively), and did an association analysis adjusted for known confounders in
      a final cohort of 249 cases and 268 controls. More than 400,000 unique SNPs were
      assayed. FINDINGS: We produced more than 200 million genotypes in 553 unique
      participants. The raw genotypes of all the controls have been posted publicly in
      a previous study of Parkinson's disease. From this effort, results of genotype
      and allele association tests have been publicly posted for 88% of stroke patients
      who provided proper consent for public release. Preliminary analysis of these
      data did not reveal any single locus conferring a large effect on risk for
      ischaemic stroke. INTERPRETATION: The data generated here comprise the first
      phase of a genome-wide association analysis in patients with stroke. Release of
      phase I results generated in these publicly available samples from each
      consenting individual makes this dataset a valuable resource for data-mining and
      augmentation.

PMID- 17434097
TI  - Epilepsy in patients with brain tumours: epidemiology, mechanisms, and
      management.
AB  - Epilepsy is common in patients with brain tumours and can substantially affect
      daily life, even if the tumour is under control. Several factors affect the
      mechanism of seizures in brain tumours, including tumour type, tumour location,
      and peritumoral and genetic changes. Prophylactic use of antiepileptic drugs is
      not recommended, and potential interactions between antiepileptic and
      chemotherapeutic agents persuades against the use of enzyme-inducing
      antiepileptic drugs. Multidrug-resistance proteins prevent the access of
      antiepileptic drugs into brain parenchyma, which partly explains why seizures are
      frequently refractory to treatment. Lamotrigine, valproic acid, and topiramate
      are first-line treatments of choice; if insufficient, add-on treatment with
      levetiracetam or gabapentin can be recommended. On the basis of clinical studies,
      we prefer to start treatment with valproic acid, adding levetiracetam if
      necessary. Risks of cognitive side-effects with antiepileptic drugs can add to
      previous damage by surgery or radiotherapy, and therefore appropriate choice and
      dose of antiepileptic drug is crucial.

PMID- 17434098
TI  - Natalizumab treatment for multiple sclerosis: recommendations for patient
      selection and monitoring.
AB  - Natalizumab is a new treatment option for patients with active relapsing
      remitting multiple sclerosis. In phase III studies, natalizumab was highly
      effective and well tolerated; however, three cases of progressive multifocal
      leucoencephalopathy (PML) were identified (estimated incidence of one per 1000;
      95% CI 0.2-2.8; mean treatment period 17.9 months). In this Review we summarise
      the current information on PML, the three confirmed cases of PML, and the results
      of an extensive safety assessment of all patients treated with natalizumab. On
      the basis of these reviews, we make recommendations for appropriate selection of
      candidates for natalizumab and pretreatment assessments. In addition, a three
      step diagnostic and management algorithm was developed to monitor natalizumab
      treated patients with multiple sclerosis for PML and other opportunistic
      infections. The algorithm includes strategies for clinical, MRI, and laboratory
      assessments. Maintaining clinical vigilance allows for early suspension of
      natalizumab in potential cases of PML, thereby increasing the opportunity for
      immune reconstitution, which may improve prognosis if PML is confirmed.

PMID- 17434099
TI  - Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis
      and management.
AB  - Wernicke's encephalopathy is an acute neuropsychiatric syndrome resulting from
      thiamine deficiency, which is associated with significant morbidity and
      mortality. According to autopsy-based studies, the disorder is still greatly
      underdiagnosed in both adults and children. In this review, we provide an update
      on the factors and clinical settings that predispose to Wernicke's
      encephalopathy, and discuss the most recent insights into epidemiology,
      pathophysiology, genetics, diagnosis, and treatment. To facilitate the diagnosis,
      we classify the common and rare symptoms at presentation and the late-stage
      symptoms. We emphasise the optimum dose of parenteral thiamine required for
      prophylaxis and treatment of Wernicke's encephalopathy and prevention of
      Korsakoff's syndrome associated with alcohol misuse. A systematic approach helps
      to ensure that patients receive a prompt diagnosis and adequate treatment.

PMID- 17434100
TI  - Stroke in China: epidemiology, prevention, and management strategies.
AB  - In this review, we examine the current status of stroke epidemiology, prevention,
      and management strategies in mainland China. The main findings suggested that
      total age-adjusted incidence of first-ever stroke in China is not very different
      from that in developed countries. Stroke incidence, mortality, and prevalence
      varied widely among different regions within China, with a noticeable north-south
      gradient. The proportion of intracerebral haemorrhage was high and reached 55% in
      one city. Hypertension is the most important risk factor for stroke. The mass
      approach combined with a high-risk approach for stroke prevention showed
      encouraging effects, and various unconventional local therapeutic traditions are
      commonly used to treat stroke in China. Several national guidelines on stroke
      prevention and treatment have been developed. Because of methodological
      limitations in the epidemiology studies, data are unreliable in terms of making
      any firm conclusions. Up-to-date, well-designed, and well-done epidemiological
      studies and therapeutic trials in China are urgently needed.

PMID- 17434101
TI  - Antiepileptic drugs: generic versus branded treatments.
AB  - Antiepileptic drugs (AEDs) are relatively cheap but high volumes of prescriptions
      mean that substantial drug-budget savings may be possible by switching from
      innovator brands to cheaper generic drugs. Such savings have been achieved in
      many other treatment areas. However, more caution may be needed in the case of
      epilepsy because of the narrow therapeutic range of most AEDs; clinical
      principles of prescribing, which include making only cautious and gradual changes
      to dosing; the health and socioeconomic impact of breakthrough seizures or
      toxicity; and the need for long-term consistency of supply. Many physicians and
      patient groups are insufficiently reassured by current definitions of similarity
      between generics and innovator brands. Switching to the cheapest generic AED may
      offer drug-budget savings that outweigh any risk to patient safety. But to date,
      this cost-benefit analysis has not been done. We propose that all changes to
      established principles of treating epilepsy are evidence based and that the risks
      of switching are clearly defined.

PMID- 17434102
TI  - When will we ever learn?

PMID- 17434104
TI  - Patient selection for NSABP B-39/RTOG 0413: have we posed the right questions in
      the right way?

PMID- 17434105
TI  - Prostate brachytherapy: a descriptive analysis from CaPSURE.
AB  - PURPOSE: The purpose of this study was to describe demographic and clinical
      characteristics in a large disease registry of prostate cancer patients treated
      with prostate brachytherapy (PB) and to identify factors influencing the use of
      supplemental external beam (SEB) radiation therapy and choice of isotope. METHODS
      AND MATERIALS: Data were abstracted from the Cancer of the Prostate Strategic
      Urologic Research Endeavor (CaPSURE), a disease registry of 11,804 men with
      various stages of prostate cancer. The study population consisted of those men
      who were diagnosed with prostate cancer between 1990 and 2003, had no prior
      history of cancer and were treated with PB (alone or with SEB). The influence of
      patient demographics, disease characteristics, and year of diagnosis on the use
      of SEB and isotope choice was examined. RESULTS: The study population included
      791 men. Six hundred nine men (77%) were treated with PB alone and 182 men (23%)
      were treated with PB and SEB. Patient demographics were not associated with the
      use of SEB. Disease characteristics were associated with the use of SEB. Patients
      treated with PB and SEB had higher pretreatment prostate-specific antigen (PSA),
      higher T-stage, higher Gleason score, and were more likely to be placed in the
      high-risk category (all p<0.01). The use of SEB increased over the period
      studied. In a multivariate analysis, patients diagnosed after 1999 were much more
      likely to receive SEB after controlling for disease characteristics (PSA, T
      stage, Gleason). Likewise, higher clinical PSA (odds ratio [OR]=1.08; 95%
      confidence interval [CI]: 1.04-1.13), higher biopsy Gleason (OR=3.64; 95% CI:
      2.60-5.09), and cT2 vs. cT1 (OR=2.06; 95% CI: 1.22-3.48) were more likely to have
      PB with SEB than PB alone. Patient demographics differed according to isotope.
      Compared to men treated with 125)I, men treated with (103)Pd were older, less
      educated, less wealthy, and less likely to have private insurance. Disease
      characteristics also differed according to isotope. Compared to men treated with
      125I, men treated with 103Pd had higher T-stages, higher Gleason scores, and were
      more likely to be placed in the intermediate- or high-risk category. The choice
      of isotope did not change over time. CONCLUSIONS: The use of SEB is associated
      with disease characteristics. SEB has increased over the period studied. Isotope
      choice is associated with patient demographics and disease characteristics.

PMID- 17434106
TI  - A prospective randomized comparison of stranded vs. loose 125I seeds for prostate
      brachytherapy.
AB  - PURPOSE: To compare seed loss and dosimetric parameters between stranded and
      loose 125I seeds (LS) for prostate brachytherapy. METHODS AND MATERIALS: Sixty
      four patients with 1997 American Joint Commission on Cancer (AJCC) clinical stage
      T1c or T2a prostate carcinoma were prospectively randomized to brachytherapy
      (144Gy) with RAPID Strand 125I seeds (RS) vs. LS (Oncura, Plymouth Meeting, PA)
      The treatment plan for each patient was devised before randomization, and was not
      modified based on the randomization. Each patient underwent magnetic resonance,
      computed tomography, and plain film radiographs on the day of the implant (Day 0)
      and 30 days later (Day 30). RESULTS: Overall, 21 of 62 patients (30%) experienced
      seed loss. Seed loss occurred in 15 of 32 of LS patients (47%) vs. 6 of 30 RS
      patients (23%; p=0.053). Mean seed loss was 1.09 in the LS patient vs. 0.43 in RS
      patients (p=0.062). Eight LS patients (25%) lost multiple seeds, compared to 3
      stranded patients (10%). Despite the lesser degree of seed loss in patients who
      received stranded seeds, they had a paradoxical trend toward lower V100 and D90
      values. CONCLUSION: This prospective randomized trial showed a strong trend
      toward a decrease in postimplant seed loss with stranded seeds. Improved seed
      retention may be more advantageous in a setting of less generous periprostatic
      coverage. The lowered risk seed migration seen with stranded seeds would
      presumably also decrease the likelihood of lung or cardiac seed embolization.

PMID- 17434107
TI  - Clinical impact of second pathology opinion: a longitudinal study of central
      genitourinary pathology review before prostate brachytherapy.
AB  - PURPOSE: To evaluate the clinical impact of pathology review before prostate
      brachytherapy. METHODS AND MATERIALS: Original and reviewing pathologists'
      reports were retrospectively collected from 1323 men treated with prostate
      brachytherapy between July 1998 and October 2005 at one institution. Statistical
      analysis was performed pre- and post-January 2002. The clinical impact of
      pathology review was evaluated. RESULTS: Gleason Score (GS) change (GS(Delta))
      occurred in 25.2% (334) of cases; GS increased in 21.6%, decreased in 2.4%, and
      diagnosed malignancy in 1.2% of cases. Post-2002, concordance in attributed GS
      improved, with GS(Delta) of 31.9-20.6%, respectively (p<0.001), and a reduction
      in the average GS(Delta) (p<0.001). The clinical impact was substantial with
      management changing in 14.8% of cases. CONCLUSION: Concordance between the
      original and reviewing pathologists' GS has improved during the study period.
      Nevertheless, discordance persists in one of five cases. Pathology review remains
      essential, if treatment decisions hinge on GS.

PMID- 17434108
TI  - Intensity modulated high-dose-rate brachytherapy boost complementary to external
      beam radiation for intermediate- and high-risk localized prostate cancer patients
      -how we do it in Lubeck/Germany.
AB  - The Kiel University technique of intensity modulated brachytherapy boost
      implantations complementary to external beam radiation used in the treatment of
      prostate cancer patients was improved by involving real-time three-dimensional
      transrectal ultrasound analysis of the prostate gland both before implantation
      and after the implantation but before capture of the transrectal ultrasound
      images for real-time dynamic treatment planning. Implantation technique,
      treatment planning procedure, and dose delivery are described as practiced at the
      University Hospital Schleswig-Holstein Campus Lubeck, Germany.

PMID- 17434109
TI  - Rectal morbidity after permanent prostate brachytherapy with dose escalation to
      biologic target volumes identified by SPECT/CT fusion.
AB  - PURPOSE: To evaluate rectal morbidity after dose escalation to biologic target
      volumes identified by capromab pendetide (ProstaScint) single-photon emission
      tomography images coregistered with computed tomography (SPECT/CT). METHODS AND
      MATERIALS: Two hundred thirty-nine consecutive patients diagnosed with T1c-T3b
      NxM0 adenocarcinoma of the prostate were treated with brachytherapy seed implant
      (SI) dose escalation to SPECT/CT-identified biologic target volumes, from
      February 1997 through December 2002. Patients received SI (n=150) or external
      beam radiation therapy plus SI (n=89). Rectal morbidity was evaluated by
      clinician scoring using the modified Radiation Therapy Oncology Group criteria.
      The median followup was 47.2 (range 24.8-96.1) months. RESULTS: The rate of acute
      Grades I and II toxicity was 29.9% and 3.7%, respectively, and chronic Grade I
      toxicity was 15.4%, 12.4%, 2.3%, and 1.8% at 1, 2, 3, and 4 years postimplant,
      respectively. Chronic Grade II toxicities were 1.8%, 1.9%, 1.5%, and 0.9% at 1,
      2, 3, and 4 years, respectively. No Grade III rectal toxicity was reported.
      Chronic Grade IV rectal toxicity was 0.5% and 0.6% at 1.5 and 2.5 years,
      respectively. Ninety-six percent of patients reported freedom from all rectal
      toxicity after 3 years. CONCLUSIONS: Dose intensification to occult tumor targets
      without increasing rectal toxicity may be achieved using SPECT/CT ProstaScint.
      Additional research to define the role of molecular imaging in prostate cancer is
      warranted.

PMID- 17434110
TI  - High-dose-rate interstitial brachytherapy in recurrent and previously irradiated
      head and neck cancers--preliminary results.
AB  - PURPOSE: Although high-dose-rate brachytherapy (HDRBT) offers significant
      advantages over low dose rate brachytherapy, there are scant data on improved
      local control (LC) and treatment-related complications in patients with recurrent
      head and neck (H&N) cancers. We report our preliminary results in patients with
      recurrent H&N cancers treated with interstitial HDRBT. METHODS AND MATERIALS:
      Thirty patients with recurrent H&N cancers were treated with HDRBT between
      September 2003 and October 2005. Seventy-seven percent (23/30) of the patients
      had either local or regional recurrence in the area of previous external beam
      radiation therapy. The treatment sites were oral cavity/oropharynx (11/30), neck
      (10/30), face/nasal cavity (6/30), and parotid bed (3/30). Whereas 18 patients
      underwent surgical resection followed by HDRBT, 3 patients were treated with
      combined external beam radiation and HDRBT, and the remaining 9 were treated with
      HDRBT alone. The dose and fractionation schedules used were 3.4Gy twice per day
      (b.i.d.) to 34Gy for postoperative cases, 4Gy b.i.d. to 20Gy when combined with
      40-50Gy external beam, and 4Gy b.i.d. to 40Gy for definitive treatment. HDRBT was
      initiated 5 days after catheter placement to allow for tissue healing. RESULTS:
      With a median followup of 12 months, 6 local recurrences were observed 1-10
      months after the procedure. The 2-year LC and overall survival outcomes for the
      entire group were 71% and 63%, respectively. Patients treated with surgical
      resection and HDRBT had an improved 2-year LC compared to the patients treated
      with HDRBT+/-external beam radiation alone (88% vs. 40%, p=0.05). Six Grade II
      and four Grade III complications were noted in five patients, all observed in the
      postoperative HDRBT group. CONCLUSION: The preliminary results of HDRBT indicate
      an acceptable LC and morbidity in recurrent H&N cancers. A planned surgical
      resection followed by HDRBT is associated with improved tumor control in these
      high-risk patients. Based on these encouraging results, prospective clinical
      trials are warranted using HDRBT in recurrent H&N cancers to decrease late
      toxicity.

PMID- 17434111
TI  - A dosimetric comparison of MammoSite high-dose-rate brachytherapy and Xoft Axxent
      electronic brachytherapy.
AB  - PURPOSE: Over 20,000 patients have been treated with partial breast irradiation
      (PBI) using the MammoSite balloon brachytherapy applicator (IBB). Recently, a new
      form of balloon-based PBI, Xoft Axxent electronic brachytherapy (KVB), which uses
      a 50-kV x-ray source, has been introduced. This analysis was undertaken to
      dosimetrically compare the results of treatment using these two methods of PBI.
      METHODS AND MATERIALS: The study population consisted of 15 patients previously
      treated with IBB. The planning CT scans from these 15 patients were used to
      construct hypothetical treatment plans using the source characteristics of the
      KVB device. The plans were then compared using the dosimetric parameters
      discussed below. RESULTS: The mean %V(90) was 99.6% vs. 99.0% (p=nonsignificant
      [ns]), the mean %V(100) was 96.5% vs. 96.5%, the mean %V(150) was 41.8% vs. 59.4%
      (p<0.05), the mean %V(200) was 11.3% vs. 32.0% (p<0.05), and the mean %V(300) was
      0.4% vs. 6.7% (p<0.05) for the IBB and KVB methods, respectively. The mean
      ipsilateral breast %V(50) was 19.8% vs. 13.0% (p<0.05), the mean ipsilateral lung
      %V(30) was 3.7% vs. 1.1% (p<0.05), and the mean heart %V(5) was 59.2% vs. 9.4%
      (p<0.05) for the IBB and KVB methods, respectively. CONCLUSIONS: The IBB and KVB
      methods of PBI offer comparable target volume coverage; however, the KVB method
      is associated with an increased volume of breast tissue in the high-dose regions
      and a decreased dose to the adjacent normal tissues.

PMID- 17434112
TI  - Necessity of chance: biological roulettes and biodiversity.
AB  - Chance plays an important role in the dynamics of biodiversity. It is largely
      responsible for the spontaneous processes leading to biological diversification.
      The mechanisms behind chance belong to two categories: on the one hand, those
      outside of biological systems, and thus belonging to their environment, on the
      other hand, those endogenous to these systems. These last mechanisms are present
      at all levels of the hierarchical organization of the living world, from genes to
      ecosystems. We propose calling them 'biological roulettes'. Like roulettes in
      casinos, they could be deterministic processes functioning in chaotic domains and
      producing results that look as though they had been generated by random
      processes. The spontaneous appearance and natural selection of these roulettes
      have led to living systems potentially adapted to new environmental conditions
      not encountered before. They may even have permitted some of them to survive
      major upheavals. Moreover, palaeontological data show that the rate of biological
      diversification accelerates and that living systems become more and more complex
      over time. That may also increase their resilience. It can be also the
      consequence of the appearance and the selection of 'biological roulettes' and of
      chance they generate. They are at the same time products and engines of the
      evolution. Without them, life would have disappeared from the Earth a long time
      ago. Thus, they are of primary importance.

PMID- 17434113
TI  - [Oogenesis of Perinereis macropus Claparede, 1870 (Annelida, Polychaeta) in the
      Gulf of Gabes (Tunisia)].
AB  - The polychaete Perinereis macropus (Claparede, 1870) (Nereididae) is present in
      the Gulf of Gabes, but its reproductive biology is unknown. An intensive study
      was conducted from August 2004 to July 2005 to characterize the life cycle of a
      population in the mouth of wadi Ferd in Gabes. The examination of sexual products
      allows us to describe the morphological oocytes aspects at different stages. The
      results show that P. macropus has an asynchronous oogenesis. Moreover, the
      biometric study of oocytes growth allows us to clarify the female sexual cycle.
      The female maturity occurs in April and the mature oocyte diameter is
      approximately 250+/-32.67 microm. However, spawning occurs in May, when the
      seawater temperature starts rising. We propose that the reproductive season
      stretches from March to June in the Gulf of Gabes.

PMID- 17434114
TI  - Yelkouan shearwater nest-cavity selection and breeding success.
AB  - We describe, for the first time, nest-cavities selected by the Mediterranean
      endemic yelkouan shearwater Puffinus yelkouan on French islands, comparing it
      with the sympatric Cory's shearwater Calonectris diomedea. By monitoring 179
      suitable cavities during four years, we show that yelkouan shearwaters select
      deeper cavities and with more winding tunnels than those selected by Cory's
      shearwaters or unoccupied cavities. Logistic regression modelling indicates that
      cavities with nest-like characteristics are not limited. We show that breeding
      success is enhanced in deeper cavities, with winding tunnels and higher block
      covers. We do not find any apparent competition between the two shearwater
      species.

PMID- 17434115
TI  - An approach to identify cold-induced low-abundant proteins in rice leaf.
AB  - A proteomic approach has been adopted to investigate the low-abundant proteins in
      rice leaf in response to cold stress. Rice seedlings were exposed to different
      temperatures, such as 5 or 10 degrees C, and samples were collected after
      different time course. To eliminate the high-abundant proteins in leaf tissues
      such as ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), proteins were
      fractionated by polyethylene glycol (PEG). The elimination of Rubisco from the
      protein samples was confirmed by Western blot analysis. The PEG fractionated
      protein samples were separated by 2-DE and visualized by silver or CBB staining.
      A total 12 up-regulated protein spots were identified using the analysis of MALDI
      TOF mass spectrometry or ESI MS/MS. We identified some novel proteins such as
      cysteine proteinase, thioredoxin peroxidase, a RING zinc finger protein-like,
      drought-inducible late embryogenesis abundant, and a fibrillin-like protein that
      had not yet been reported in the earlier reports on cold proteomic analysis. The
      identification of some novel low-abundant proteins in response to cold stress may
      provide a new homeostasis to develop enhanced cold tolerance transgenic plants.
      Thus, we propose that a PEG fractionation system can be used as an influential
      protein extraction method from the leaf samples, which can lead to knowledge of
      the expression pattern of low-abundant proteins in response to various biotic or
      abiotic stresses.

PMID- 17434116
TI  - [Effects of the methanolic extract of Chrysanthemum trifurcatum (Desf.) Batt. and
      Trab. on rat duodenal motility].
AB  - The effect of the methanolic extract of flowers of Chrysanthemum trifurcatum
      (Desf.) Batt. and Trab. Var. macrocephalum (viv.) Beg. on the rat duodenum smooth
      muscle motility was examined in vitro. The extract has shown dose-dependent
      stimulator effects on the amplitude of the spontaneous contractions. With 0.1
      g/ml of extract, maximal stimulation was obtained. With that dose, the variation
      (%) was significantly 1050 +/- 13 (P<0.001) compared with control and represented
      80 +/- 5.83% (P<0.001) of the maximum effect of acetylcholine. Atropine (2
      microg/ml) reduced by 81 +/- 4% (P<0.05) the spasmogenic effects of C.
      trifurcatum and by 92 +/- 3% (P<0.05) the acetylcholine effects, while papaverine
      (2 microg/ml) completely inhibited the spasmogenic effects of extract. With a
      fixed dose of acetylcholine added (20 microg/ml), the extract increases its
      effect, but acetylcholine decreases its action. These results suggested that the
      methanolic extract of C. trifurcatum could stimulate duodenal smooth muscle
      contractions through muscarinic receptors. Thy explain the respective traditional
      use of plant in gastrointestinal problems, especially constipation.

PMID- 17434117
TI  - The distribution and life cycle of the dinoflagellate Spatulodinium
      pseudonoctiluca (Dinophyceae, Noctilucales) in the northeastern English Channel.
AB  - The distribution of Spatulodinium (= Gymnodinium) pseudonoctiluca (Pouchet) J.
      Cachon & M. Cachon has been investigated for eight years (1998-2005) in the
      northeastern English Channel, type locality of the species and its immature
      stages. The species can be found after the spring diatom bloom from late May to
      October. The highest abundance was found in June 2004 after the Phaeocystis
      bloom. Exceptionally, the Phaeocystis bloom was absent in 2005 and only several
      specimens of S. pseudonoctiluca were observed. The immature and mature stages of
      Spatulodinium nearly always co-occurred. No other kofoidiniaceans such as
      Kofoidinium or Pomatodinium were observed. The first stages of the development of
      Spatulodinium can easily confuse with gymnodiniaceans. The transformation of the
      stage 'D', which has been described as Gymnodinium lebouriae (= G. fulgens) or
      Gymnodinium conicum (= G. viridis), into the mature stage, is illustrated. The
      stage 'D' originates from a cluster of pairs of smaller cells joined by an
      elongate episome. In the boreal Atlantic Ocean, Spatulodinium pseudonoctiluca, a
      single species whose life stages are often reported as separate species, is
      especially adapted to a strongly fluctuant environment.

PMID- 17434118
TI  - Differential tolerance to iron deficiency of chickpea varieties and Fe resupply
      effects.
AB  - The consequences of direct iron deficiency and iron resupply were evaluated
      during development stages of two Tunisian chickpea varieties (INRAT88 and
      Chetoui) cultivated in continuously aerated solution with or without 20 muM Fe.
      The chlorosis score was estimated during culture. Growth parameters, chlorophyll
      concentration, acidification capacity and Fe concentration were measured every
      three days during the 21-day treatment. After three weeks of treatment, the
      chlorosis index was 3-fold higher in Chetoui than in INRAT88, and a considerable
      decrease of chlorophyll concentration was observed in Chetoui plants since the
      6th day of -Fe deprivation. Iron deficiency significantly inhibited whole-plant
      biomass deposition in both varieties. However, the growth reduction appeared
      earlier, and was more pronounced in Chetoui than in INRAT88. The whole-plant Fe
      content decreased dramatically under deficient conditions, and we note an Fe
      enrichment in shoots at the expense of roots. The sensitivity of Chetoui as
      compared to INRAT88 was confirmed by the behaviour of resupplied (-Fe/+Fe)
      plants. In fact, the addition of iron to deficient plants had no significant
      effect in Chetoui, whereas it led to a total recovery in INRAT88. The capacity of
      INRAT88 to maintain plant growth and to preserve adequate chlorophyll synthesis
      under limited iron conditions is related to its better Fe-use efficiency, in
      addition to its capacity to rapidly recover from this stress.

PMID- 17434119
TI  - Expected impact of agriculture expansion on the world avifauna.
AB  - Agriculture expansion is a major cause of the current biodiversity decline. From
      the knowledge of the average bird densities in the terrestrial biomes, and using
      forecasts of biome conversions associated to agriculture expansion between 1990
      and 2050, we estimate that these conversions would reduce by 8 to 26% the global
      avifauna, in number of individuals, depending on socio-economic scenarios and
      farmland management. Then, adding these values to previous estimates, we estimate
      that 27-44% of the bird species could be lost due to agriculture expansion from
      Neolithic to 2050.

PMID- 17434120
TI  - Local-scale species-energy relationships in fish assemblages of some forested
      streams of the Bolivian Amazon.
AB  - Productivity (trophic energy) is one of the most important factors promoting
      variation in species richness. A variety of species-energy relationships have
      been reported, including monotonically positive, monotonically negative, or
      unimodal (i.e. hump-shaped). The exact form of the relationship seems to depend,
      among other things, on the spatial scale involved. However, the mechanisms behind
      these patterns are still largely unresolved, although many hypotheses have been
      suggested. Here we report a case of local-scale positive species-energy
      relationship. Using 14 local fish assemblages in tropical forested headwater
      streams (Bolivia), and after controlling for major local abiotic factors usually
      acting on assemblage richness and structure, we show that rising energy
      availability through leaf litter decomposition rates allows trophically
      specialized species to maintain viable populations and thereby to increase
      assemblage species richness. By deriving predictions from three popular
      mechanistic explanations, i.e. the 'increased population size', the 'consumer
      pressure', and the 'specialization' hypotheses, our data provide only equivocal
      support for the latter.

PMID- 17434121
TI  - Mitochondrial DNA variability in Giraffa camelopardalis: consequences for
      taxonomy, phylogeography and conservation of giraffes in West and central Africa.
AB  - The giraffe (Giraffa camelopardalis) still survives in four countries of West and
      central Africa. The populations of Niger and Cameroon are generally assigned to
      the subspecies peralta, but those of Chad and the Central African Republic are
      taxonomically problematic, as they are referred to as either peralta, or
      antiquorum, or congoensis. In this study, a mitochondrial fragment of 1765
      nucleotide sites, covering the complete cytochrome b gene, three transfer RNAs
      and a large part of the control region, was sequenced to assess the relationships
      between several populations of giraffe. The phylogenetic analyses performed on
      the 12 identified haplotypes indicate that northern giraffes constitute a natural
      group, distinct from that of southern giraffes. Surprisingly, the giraffes of
      Niger are found to be more closely related to the giraffes of East Africa
      (subspecies rothschildi and reticulata) than to those of central Africa. We
      conclude therefore that the subspecies peralta contains only the Niger giraffes,
      whereas the subspecies antiquorum includes all populations living in Cameroon,
      Chad, the Central African Republic, and southwestern Sudan. We suggest that the
      ancestor of the Nigerian giraffe dispersed from East to North Africa during the
      Quaternary period and thereafter migrated to its current Sahelian distribution in
      West Africa, in response to the development of the Sahara desert. This hypothesis
      implies that Lake Mega-Chad acted as a strong geographical barrier during the
      Holocene, preventing any contact between the subspecies peralta and antiquorum.
      Our study has direct implications for conservation management, as we show that no
      subspecies peralta is represented in any European zoos, only in Niger, with a
      small population of less than 200 individuals.

PMID- 17434122
TI  - Hydrogen peroxide sensing and signaling.
AB  - It is well established that oxidative stress is an important cause of cell damage
      associated with the initiation and progression of many diseases. Consequently,
      all air-living organisms contain antioxidant enzymes that limit oxidative stress
      by detoxifying reactive oxygen species, including hydrogen peroxide. However, in
      eukaryotes, hydrogen peroxide also has important roles as a signaling molecule in
      the regulation of a variety of biological processes. Here, we will discuss the
      molecular mechanisms by which hydrogen peroxide is sensed and the increasing
      evidence that antioxidant enzymes play multiple, key roles as sensors and
      regulators of signal transduction in response to hydrogen peroxide.

PMID- 17434123
TI  - Mapping protein-protein interactions for the yeast ABC transporter Ycf1p by
      integrated split-ubiquitin membrane yeast two-hybrid analysis.
AB  - The ATP binding cassette (ABC) transporters are important in human health and
      disease and represent the largest family of transmembrane proteins; however,
      their highly hydrophobic nature complicates the use of standard biochemical
      approaches to identify interacting proteins. Here, we report the development of a
      modified version of the split-ubiquitin membrane yeast two-hybrid (MYTH)
      technology using genomically integrated "bait" constructs, hence the designation
      iMYTH. We used iMYTH in a library-screening format and identified six potential
      interacting partners of the yeast ABC transporter Ycf1p. Strains deleted for
      several of these genes result in arsenite sensitivity similar to a Deltaycf1
      strain. Transport assays show that one of these, Tus1p, a guanine nucleotide
      exchange factor (GEF) for the small GTPase Rho1p, is a Rho1p-dependent-positive
      regulator of Ycf1p. Our study provides proof of principle that iMYTH is an ideal
      methodology to identify physiological interactors and regulators of ABC
      transporters and other yeast transmembrane proteins.

PMID- 17434124
TI  - Hsp70 chaperone ligands control domain association via an allosteric mechanism
      mediated by the interdomain linker.
AB  - Hsp70 chaperones assist in protein folding, disaggregation, and membrane
      translocation by binding to substrate proteins with an ATP-regulated affinity
      that relies on allosteric coupling between ATP-binding and substrate-binding
      domains. We have studied single- and two-domain versions of the E. coli Hsp70,
      DnaK, to explore the mechanism of interdomain communication. We show that the
      interdomain linker controls ATPase activity by binding to a hydrophobic cleft
      between subdomains IA and IIA. Furthermore, the domains of DnaK dock only when
      ATP binds and behave independently when ADP is bound. Major conformational
      changes in both domains accompany ATP-induced docking: of particular importance,
      some regions of the substrate-binding domain are stabilized, while those near the
      substrate-binding site become destabilized. Thus, the energy of ATP binding is
      used to form a stable interface between the nucleotide- and substrate-binding
      domains, which results in destabilization of regions of the latter domain and
      consequent weaker substrate binding.

PMID- 17434125
TI  - The eukaryotic translation initiation factors eIF1 and eIF1A induce an open
      conformation of the 40S ribosome.
AB  - Initiation of translation is the process by which initiator tRNA and the start
      codon of mRNA are positioned in the ribosomal P site. In eukaryotes, one of the
      first steps involves the binding of two small factors, eIF1 and eIF1A, to the
      small (40S) ribosomal subunit. This facilitates tRNA binding, allows scanning of
      mRNA, and maintains fidelity of start codon recognition. Using cryo-EM, we have
      obtained 3D reconstructions of 40S bound to both eIF1 and eIF1A, and with each
      factor alone. These structures reveal that together, eIF1 and eIF1A stabilize a
      conformational change that opens the mRNA binding channel. Biochemical data
      reveal that both factors accelerate the rate of ternary complex (eIF2*GTP*Met
      tRNA(i)(Met)) binding to 40S but only eIF1A stabilizes this interaction. Our
      results suggest that eIF1 and eIF1A promote an open, scanning-competent
      preinitiation complex that closes upon start codon recognition and eIF1 release
      to stabilize ternary complex binding and clamp down on mRNA.

PMID- 17434126
TI  - Nuclear export of ribosomal 60S subunits by the general mRNA export receptor
      Mex67-Mtr2.
AB  - The yeast Mex67-Mtr2 complex and its homologous metazoan counterpart TAP-p15
      operate as nuclear export receptors by binding and translocating mRNA through the
      nuclear pore complexes. Here, we show how Mex67-Mtr2 can also function in the
      nuclear export of the ribosomal 60S subunit. Biochemical and genetic studies
      reveal a previously unrecognized interaction surface on the NTF2-like scaffold of
      the Mex67-Mtr2 heterodimer, which in vivo binds to pre-60S particles and in vitro
      can interact with 5S rRNA. Crucial structural requirements for this binding
      platform are loop insertions in the middle domain of Mex67 and Mtr2, which are
      absent from human TAP-p15. Notably, when the positively charged amino acids in
      the Mex67 loop are mutated, interaction of Mex67-Mtr2 with pre-60S particles and
      5S rRNA is inhibited, and 60S subunits, but not mRNA, accumulate in the nucleus.
      Thus, the general mRNA exporter Mex67-Mtr2 contains a distinct electrostatic
      interaction surface for transporting 60S preribosomal cargo.

PMID- 17434127
TI  - Regulation of HIF-1alpha stability through S-nitrosylation.
AB  - Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional factor. Under
      normal oxygen tension, HIF-1 activity is usually suppressed due to the rapid,
      oxygen-dependent degradation of one of its two subunits, HIF-1alpha. Here we
      report that normoxic HIF-1 activity can be upregulated through NO-mediated S
      nitrosylation and stabilization of HIF-1alpha. In murine tumors, exposure to
      ionizing radiation stimulated the generation of NO in tumor-associated
      macrophages. As a result, the HIF-1alpha protein is S-nitrosylated at Cys533
      (through "biotin switch" assay) in the oxygen-dependent degradation domain, which
      prevents its destruction. Importantly, this mechanism appears to be independent
      of the prolylhydroxylase-based pathway that is involved in oxygen-dependent
      regulation of HIF-1alpha. Selective disruption of this S-nitrosylation
      significantly attenuated both radiation-induced and macrophage-induced activation
      of HIF-1alpha. This interaction between NO and HIF-1 sheds new light on their
      involvement in tumor response to treatment as well as mammalian inflammation
      process in general.

PMID- 17434128
TI  - Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding
      preference of CBP from p53 to NF-kappaB.
AB  - CBP plays a central role in coordinating and integrating multiple signaling
      pathways. Competition between NF-kappaB and p53 for CBP is a crucial determinant
      of whether a cell proliferates or undergoes apoptosis. However, how the CBP
      dependent crosstalk between these two transcription factors is regulated remains
      unclear. Here, we show that IKKalpha phosphorylates CBP at serine 1382 and serine
      1386 and consequently increases CBP's HAT and transcriptional activities.
      Importantly, such phosphorylation enhances NF-kappaB-mediated gene expression and
      suppresses p53-mediated gene expression by switching the binding preference of
      CBP from p53 to NF-kappaB, thus promoting cell growth. The CBP phosphorylation
      also correlates with constitutive IKKalpha activation in human lung tumor tissue
      compared with matched nontumor lung tissue. Our results suggest that
      phosphorylation of CBP by IKKalpha regulates the CBP-mediated crosstalk between
      NF-kappaB and p53 and thus may be a critical factor in the promotion of cell
      proliferation and tumor growth.

PMID- 17434129
TI  - S. pombe LSD1 homologs regulate heterochromatin propagation and euchromatic gene
      transcription.
AB  - LSD1 represses and activates transcription by demethylating histone H3K4me and
      H3K9me, respectively. Genetic ablation of the S. pombe homologs, splsd1 and
      splsd2, resulted in slow growth and lethality, respectively, underscoring their
      physiological importance. spLsd1 and spLsd2 form a stable protein complex, which
      exhibits demethylase activity toward methylated H3K9 in vitro. Both proteins were
      associated with the heterochromatin boundary regions and euchromatic gene
      promoters. Loss of spLsd1 resulted in increased H3K9 methylation accompanied by
      reduced euchromatic gene transcription and heterochromatin propagation. Removal
      of the H3K9 methylase Clr4 partially suppressed the slow growth phenotype of
      splsd1Delta. Conversely, catalytically inactivating point mutations in the splsd1
      and splsd2 genes partially mimicked the growth and heterochromatin propagation
      phenotypes. Taken together, these findings suggest the importance of both
      enzymatic and nonenzymatic roles of spLsd1 in regulating heterochromatin
      propagation and euchromatic transcription and also suggest that misregulation of
      spLsd1/2 is likely to impact the epigenetic state of the cell.

PMID- 17434130
TI  - Heterochromatin formation in Drosophila is initiated through active removal of
      H3K4 methylation by the LSD1 homolog SU(VAR)3-3.
AB  - Epigenetic indexing of chromatin domains by histone lysine methylation requires
      the balanced coordination of methyltransferase and demethylase activities. Here,
      we show that SU(VAR)3-3, the Drosophila homolog of the human LSD1 amine oxidase,
      demethylates H3K4me2 and H3K4me1 and facilitates subsequent H3K9 methylation by
      SU(VAR)3-9. Su(var)3-3 mutations suppress heterochromatic gene silencing, display
      elevated levels of H3K4me2, and prevent extension of H3K9me2 at pericentric
      heterochromatin. SU(VAR)3-3 colocalizes with H3K4me2 in interband regions and is
      abundant during embryogenesis and in syncytial blastoderm, where it appears
      concentrated at prospective heterochromatin during cycle 14. In embryos of
      Su(var)3-3/+ females, H3K4me2 accumulates in primordial germ cells, and the
      deregulated expansion of H3K4me2 antagonizes heterochromatic H3K9me2 in
      blastoderm cells. Our data indicate an early developmental function for the
      SU(VAR)3-3 demethylase in controlling euchromatic and heterochromatic domains and
      reveal a hierarchy in which SU(VAR)3-3-mediated removal of activating histone
      marks is a prerequisite for subsequent heterochromatin formation by H3K9
      methylation.

PMID- 17434131
TI  - Structural basis for converting a general transcription factor into an operon
      specific virulence regulator.
AB  - RfaH, a paralog of the general transcription factor NusG, is recruited to
      elongating RNA polymerase at specific regulatory sites. The X-ray structure of
      Escherichia coli RfaH reported here reveals two domains. The N-terminal domain
      displays high similarity to that of NusG. In contrast, the alpha-helical coiled
      coil C domain, while retaining sequence similarity, is strikingly different from
      the beta barrel of NusG. To our knowledge, such an all-beta to all-alpha
      transition of the entire domain is the most extreme example of protein fold
      evolution known to date. Both N domains possess a vast hydrophobic cavity that is
      buried by the C domain in RfaH but is exposed in NusG. We propose that this
      cavity constitutes the RNA polymerase-binding site, which becomes unmasked in
      RfaH only upon sequence-specific binding to the nontemplate DNA strand that
      triggers domain dissociation. Finally, we argue that RfaH binds to the beta'
      subunit coiled coil, the major target site for the initiation sigma factors.

PMID- 17434132
TI  - Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate
      recognition by SCF ubiquitin ligases.
AB  - The ubiquitin-mediated proteolysis of cyclin E plays a central role in cell-cycle
      progression, and cyclin E accumulation is a common event in cancer. Cyclin E
      degradation is triggered by multisite phosphorylation, which induces binding to
      the SCF(Fbw7) ubiquitin ligase complex. Structures of the Skp1-Fbw7 complex bound
      to cyclin E peptides identify a doubly phosphorylated pThr380/pSer384 cyclin E
      motif as an optimal, high-affinity degron and a singly phosphorylated pThr62
      motif as a low-affinity one. Biochemical data indicate that the closely related
      yeast SCF(Cdc4) complex recognizes the multisite phosphorylated Sic1 substrate
      similarly and identify three doubly phosphorylated Sic1 degrons, each capable of
      high-affinity interactions with two Cdc4 phosphate binding sites. A model that
      explains the role of multiple cyclin E/Sic1 degrons is provided by the findings
      that Fbw7 and Cdc4 dimerize, that Fbw7 dimerization enhances the turnover of a
      weakly associated cyclin E in vivo, and that Cdc4 dimerization increases the rate
      and processivity of Sic1 ubiquitination in vitro.

PMID- 17434133
TI  - A network of multiple regulatory layers shapes gene expression in fission yeast.
AB  - Gene expression is controlled at multiple layers, and cells may integrate
      different regulatory steps for coherent production of proper protein levels. We
      applied various microarray-based approaches to determine key gene-expression
      intermediates in exponentially growing fission yeast, providing genome-wide data
      for translational profiles, mRNA steady-state levels, polyadenylation profiles,
      start-codon sequence context, mRNA half-lives, and RNA polymerase II occupancy.
      We uncovered widespread and unexpected relationships between distinct aspects of
      gene expression. Translation and polyadenylation are aligned on a global scale
      with both the lengths and levels of mRNAs: efficiently translated mRNAs have
      longer poly(A) tails and are shorter, more stable, and more efficiently
      transcribed on average. Transcription and translation may be independently but
      congruently optimized to streamline protein production. These rich data sets, all
      acquired under a standardized condition, reveal a substantial coordination
      between regulatory layers and provide a basis for a systems-level understanding
      of multilayered gene-expression programs.

PMID- 17434134
TI  - Evidence for the role of self-priming in epistemic action: expertise and the
      effective use of memory.
AB  - Epistemic actions are physical actions people take to simplify internal problem
      solving rather than to move closer to an external goal. When playing the video
      game Tetris, for instance, experts routinely rotate falling shapes more than is
      strictly needed to place the shapes. Maglio and Kirsh [Kirsh, D., & Maglio, P.
      (1994). On distinguishing epistemic from pragmatic action. Cognitive Science, 18,
      513-549; Maglio, P. P. (1995). The computational basis of interactive skill. PhD
      thesis, University of California, San Diego] proposed that such actions might
      serve the purpose of priming memory by external means, reducing the need for
      internal computation (e.g., mental rotation), and resulting in performance
      improvements that exceed the cost of taking additional actions. The present study
      tests this priming hypothesis in a set of four experiments. The first three
      explored precisely the conditions under which priming produces benefits. Results
      showed that presentation of multiple orientations of a shape led to faster
      responses than did presentation of a single orientation, and that this effect
      depended on the interval between preview and test. The fourth explored whether
      the benefit of seeing shapes in multiple orientations outweighs the cost of
      taking the extra actions to rotate shapes physically. Benefits were measured
      using a novel statistical method for mapping reaction-time data onto an estimate
      of the increase in processing capacity afforded by seeing multiple orientations.
      Cost was measured using an empirical estimate of time needed to take action in
      Tetris. Results showed that indeed the increase in internal processing capacity
      obtained from seeing shapes in multiple orientations outweighed the time to take
      extra actions.

PMID- 17434135
TI  - Au nanoparticle network-type thin films formed via mixed assembling and cross
      linking route for biosensor application: quartz crystal microbalance study.
AB  - We have investigated a means of producing Au nanoparticle network-type thin films
      that are derived by a one-step mixed-assembly cross-linking route, can avoid
      nonspecific interactions, and provide maximum binding to a specific target.
      Although a stepwise layer-by-layer construction method exists, our goal is to
      seek an alternative and simpler pathway for preparing thin films such as
      electrode nanomaterials. The model system consisting of Au nanoparticles, 1,6
      hexananedithiol (HDT) cross-linkers, and 3-mercaptopropionic acid (MPA) captures
      was studied. The mixing of these three components in solutions allowed sequential
      assembly, cross-linking, and eventual precipitation of the network-type thin
      films on a Au substrate. Characterization of the films was carried out using UV
      visible spectroscopy, cyclic voltammetry, and a quartz crystal microbalance. Such
      a thin film can be useful in biosensing and surface-coating applications. By
      controlling the ratio of HDT and MPA, we made Au nanoparticle network-type thin
      films on which goat-anti-human IgG antibodies that were immobilized can bind
      specifically to IgG with negligible nonspecific binding.

PMID- 17434136
TI  - [Intratumoral chemotherapy: experimental data and applications to head and neck
      tumors].
AB  - OBJECTIVE: Intratumoral chemotherapy consists in the direct intratumoral
      injection of the anticancer drugs. Despite its simple and logical principle it
      remains relatively little used. MATERIAL AND METHODS: This work reviews and
      analyses the national and international literature about experimental and
      clinical studies of intratumoral chemotherapy. RESULTS: Numerous experimental
      studies validated its theoretical advantages compared with the intravenous one:
      drug intratumoral concentration increase, antitumoral activity improvement and
      systemic toxicity decrease. But they also underlined its limits: the high
      clearance and the non-homogeneous drug diffusion. Research works led to the
      improvement of the results and performed clinical trials with slow release
      devices (microspheres, collagen matrix with or without vasoconstrictive agent),
      anticancer drug in an aqueous solution with a vasoconstrictive agent,
      intratumoral injection in association with electrochemotherapy or radiotherapy.
      These trials showed the feasibility of this technique with, in recurrent tumors,
      response rate between 27 and 50% and an increase in quality of life. The more
      frequent adverse effects were pain in 24 to 80% of cases, ulceration, necrosis
      and oedema of the treated locations in 53 to 87,4% of cases and during the use of
      vasoconstrictive agents systemic effects like arterial hypertension and
      extrasystoles. CONCLUSIONS: Intratumoral chemotherapy is an effective therapeutic
      even when used after the classical treatments. Improvements are necessary to
      define the best drugs, injection technique, treatment periodicity and
      indications. Intratumoral chemotherapy deserves better interest at the moment
      where drugs and antibodies limit their action to the cancer cells preserving the
      healthy ones.

PMID- 17434137
TI  - [Multifocal nodular oncocytosis hyperplasia of the parotid gland].
AB  - OBJECTIVES: Oncocytic lesions rarely affect the parotid gland, accounting for
      less than 1% of all salivary lesions. The WHO classification described three main
      types: diffuse oncocytosis, focal nodular oncocytosis hyperplasia, and
      oncocytoma. Multifocal nodular oncocytosis hyperplasia of the parotid gland
      represents an extremely rare, non-tumorous pathology of the parotid gland.
      MATERIAL AND METHODS: We report a case of multifocal nodular oncocytosis
      hyperplasia of the parotid gland in a 70-year-old woman who was referred for a
      left preauricular mass that had gradually increased in size over the last 2
      years. No lymph node of the neck was palpable. RESULTS: MRI demonstrated multiple
      bilateral lesions of the parotid glands. Total parotidectomy, preserving the
      facial nerve, was performed. CONCLUSION: We discuss the physiopathology and the
      treatment of multifocal nodular oncocytosis hyperplasia and provide a review of
      the literature.

PMID- 17434138
TI  - [Rectal pentobarbital sedation for children undergoing auditory brainstem
      response testing].
AB  - OBJECTIVES: The aim of our study was to determine if rectal sedation with
      pentobarbital sodium provides safe and effective sedation for children undergoing
      auditory brainstem response (ABR) testing. MATERIAL AND METHODS: A prospective
      study was conducted in the ENT pediatric department of Robert Debre's hospital
      (APHP, Paris). 68 children under 8 years of age were given rectal pentobarbital
      for ABR testing at a dosage of about 5 mg/kg. RESULTS: 61 children of 68 (89.7%)
      were adequately sedated with rectal pentobarbital. The mean elapsed time from
      drug administration to full sedation was 36,1 minutes. No adverse event was
      reported in 84.1% of children. CONCLUSION: Pentobarbital provides safe and
      effective sedation. Rectal administration is easy, painless and with brief
      duration of action. It's a good alternative to general anesthesia for young
      children undergoing ABR testing.

PMID- 17434139
TI  - [Seromucous otitis].
AB  - OBJECTIVES: Otitis media with effusion are defined as the persistence of middle
      ear effusion for more than 3 weeks. If the diagnostic is easy, questions remain
      about pathogeny and treatment. MATERIALS AND METHODS: Literature was reviewed
      regarding the pathogeny and the best treatment strategy. RESULTS: Except in the
      case of middle ear effusion due to trauma, effusion is an exudate due to mucous
      cell metaplasia. The main causal factor is middle ear inflammation, which is
      secondary to viral or bacterial infection. Inflammation causes dysfunction of the
      sodium transports in the middle ear. Responsibility of the otitis media with
      effusion in the genesis of the various chronic otitis media remains
      controversial. Treatment is justified when otitis media last more than 3 months,
      that is to say few months observation is required. The aim of treatment is to
      reduce local inflammation and to treat effusion. Prevention and treatment of
      local inflammation is difficult. Indeed, it is difficult to avoid rhinitis that
      is mainly viral. Effusion must be treated in order to avoid local middle ear
      deterioration and language deficiency. Insertion of tympanostomy tube is the only
      effective treatment. It decreases middle ear depression and Eustachian tube
      obstruction and restores the mucociliary clearance. Adenoidectomy and
      amygdalectomy are not effective in otitis media with effusion but, in association
      with tympanostomy tube, could decrease recurrence of acute otitis media.
      CONCLUSION: Otitis media with effusion remains a frequent disorder, for which the
      only effective treatment is the tympanostomy tube.

PMID- 17434140
TI  - Identification of disease-associated proteins by proteomic approach in ankylosing
      spondylitis.
AB  - Ankylosing spondylitis (AS) is a chronic systemic inflammatory disorder of the
      axial skeleton and shows significant inherited susceptibility. Auto-immune
      responses have been traditionally considered as a putative pathogenetic event in
      AS. However, no consistent self-antigen has been identified to responsible for
      the disorders in AS to this day. In this study, serum protein profiles of AS
      patients and healthy controls from a large Chinese AS family were investigated by
      two dimensional electrophoresis analysis. A group of four highly expressed
      protein spots was observed in all AS patients' profiles and subsequently
      identified as isoforms of haptoglobin precursor (pre-Hp) by ESI-Q-TOF MS/MS.
      Increased expression of haptoglobin precursor were also observed in sera of
      sporadic AS patients. Moreover, bioinformatics analysis revealed epitopes derived
      from haptoglobin precursor with high affinity binding to HLA-B( *)2705, a primary
      subtype associated with AS. These results indicate that pre-Hp may be involved in
      the pathogenesis of AS.

PMID- 17434141
TI  - Fatty acid represses insulin receptor gene expression by impairing HMGA1 through
      protein kinase Cepsilon.
AB  - It is known that free fatty acid (FFA) contributes to the development of insulin
      resistance and type2 diabetes. However, the underlying mechanism in FFA-induced
      insulin resistance is still unclear. In the present investigation we have
      demonstrated that palmitate significantly (p <0.001) inhibited insulin-stimulated
      phosphorylation of PDK1, the key insulin signaling molecule. Consequently, PDK1
      phosphorylation of plasma membrane bound PKCepsilon was also inhibited.
      Surprisingly, phosphorylation of cytosolic PKCepsilon was greatly stimulated by
      palmitate; this was then translocated to the nuclear region and associated with
      the inhibition of insulin receptor (IR) gene transcription. A PKCepsilon
      translocation inhibitor peptide, epsilonV1, suppressed this inhibitory effect of
      palmitate, suggesting requirement of phospho-PKCepsilon migration to implement
      palmitate effect. Experimental evidences indicate that phospho-PKCepsilon
      adversely affected HMGA1. Since HMGA1 regulates IR promoter activity, expression
      of IR gene was impaired causing reduction of IR on cell surface and that
      compromises with insulin sensitivity.

PMID- 17434142
TI  - The mitochondrial tRNA(Glu) A14693G mutation may influence the phenotypic
      manifestation of ND1 G3460A mutation in a Chinese family with Leber's hereditary
      optic neuropathy.
AB  - We report here the clinical, genetic, and molecular characterization of one Han
      Chinese family with maternally transmitted Leber's hereditary optic neuropathy
      (LHON). Three of seven matrilineal relatives in this family exhibited the
      variable degree of central vision loss at the age of 12, 14, and 16 years old,
      respectively. Sequence analysis of the complete mitochondrial DNA in this
      pedigree revealed the presence of the ND1 G3460A mutation and 47 other variants,
      belonging to the Asian haplogroup M7b2. The G3460A mutation is present at
      homoplasmy in matrilineal relatives of this Chinese family. Of other variants,
      the homoplasmic A14693G mutation is of special interest as it was implicated to
      be associated with other mitochondrial disorders. This mutation is located at the
      TpsiC-loop, at conventional position 54 of tRNA(Glu). The uridine at this
      position (U54), which is highly conserved from bacteria to human mitochondria,
      has been implicated to be important for tRNA structure and function. Thus, the
      A14693G mutation may alter the tertiary structure of this tRNA, cause a failure
      in this tRNA metabolism, thereby worsening the mitochondrial dysfunction
      associated with the primary G3460A mutation. Therefore, the tRNA(Glu) A14693G
      mutation may have a potential modifier role in the phenotypic manifestation of
      the primary LHON-associated G3460A mutation in this Chinese family.

PMID- 17434143
TI  - Alignment of two-dimensional electrophoresis gels.
AB  - Two-dimensional electrophoresis is a major separating technique for proteins in
      proteomics. Alignment of gel images is critical for intra-laboratory or even more
      difficult inter-laboratory gel comparisons. In the paper, we propose a novel
      iterative closest point (ICP) method for 2D-gel electrophoresis image alignment.
      The paper seeks to introduce an information theoretic measure as one part of
      distance metric to gel image alignment. We combine intensity information of spots
      with geometric information of landmarks by applying information potential idea.
      The proposed method has been applied to both synthetic and real gel images
      accessible in public 2D-electrophoresis gel protein databases. The high accuracy
      and robustness of the algorithm indicate that it is promising for gel image
      alignment.

PMID- 17434144
TI  - siRNA targeting PLK-1 induces apoptosis of synoviocytes in rheumatoid arthritis.
AB  - Polo-like kinase-1 (PLK-1) is a member of the PLK family and participates in the
      control of cell mitosis. Here, we show that immunoreactive PLK-1 is strongly
      expressed in synoviocytes and some infiltrative mononuclear cells in synovial
      tissues from patients with rheumatoid arthritis (RA), while patients with
      osteoarthritis and injury show little or no expression of PLK-1 in synovial
      tissues. Western blot analysis shows that PLK is expressed and its expression is
      enhanced by IL-1beta in RA synoviocytes. IL-1beta also enhanced the cell growth
      of RA synoviocytes. Moreover, siRNA targeted against PLK-1 significantly
      decreases the expression of PLK-1 of RA synoviocytes stimulated by IL-1beta and
      suppresses the proliferation of these synoviocytes through apoptosis. These
      findings suggest that PLK-1 plays a critical role in the proliferation of RA
      synoviocytes leading to bone destruction, and siRNA against PLK-1 is potentially
      useful for the treatment of RA.

PMID- 17434145
TI  - Phosphorylation of ataxin-3 by glycogen synthase kinase 3beta at serine 256
      regulates the aggregation of ataxin-3.
AB  - Machado-Joseph disease (MJD) is a dominant neurodegenerative disorder caused by
      an expansion of the polyglutamine tract in MJD-1 gene product, ataxin-3.
      Recently, studies show that phosphorylation of polyglutamine disease proteins,
      such as huntingtin, ataxin-1 and DRPLA, plays an important role in regulating
      pathogenesis. However, the kinase that phosphorylates ataxin-3 remains unknown.
      Here we show that S256 site in ataxin-3 is phosphorylated by GSK 3beta. Moreover,
      S256A mutant of expanded ataxin-3 forms high molecular weight protein
      aggregation, whereas S256D mutant and expanded ataxin-3 without mutation on this
      site are monomeric. The molecular chaperone Hsp70 represses the aggregation of
      S256A mutant. Our results imply that phosphorylation of serine 256 in ataxin-3 by
      GSK 3beta regulates ataxin-3 aggregation.

PMID- 17434146
TI  - Senescent phenotypes of skin fibroblasts from patients with Tangier disease.
AB  - Tangier disease (TD) is characterized by a deficiency of high density lipoprotein
      (HDL) in plasma and patients with TD have an increased risk for coronary artery
      disease (CAD). Recently, we reported that fibroblasts from TD exhibited large and
      flattened morphology, which is often observed in senescent cells. On the other
      hand, data have accumulated to show the relationship between cellular senescence
      and development of atherosclerotic CAD. The aim of the present study was to
      investigate whether TD fibroblasts exhibited cellular senescence. The
      proliferation of TD fibroblasts was gradually decreased at population doubling
      level (PDL) approximately 10 compared with control cells. TD cells practically
      ceased proliferation at PDL approximately 30. DNA synthesis was markedly
      decreased in TD fibroblasts. TD cells exhibited a higher positive rate for
      senescence-associated beta-galactosidase (SA-beta-gal), which is one of the
      biomarkers of cellular senescence in vitro. These data showed that TD cells
      reached cellular senescence at an earlier PDL compared with controls. Although,
      there was no difference in the telomere length of fibroblasts between TD and
      controls at the earlier passage (PDL 6), the telomere length of TD cells was
      shorter than that of controls at the late passage (PDL 25). Taken together, the
      current study demonstrates that the late-passaged TD fibroblasts showed senescent
      phenotype in vitro, which might be related to the increased cardiovascular
      manifestations in TD patients.

PMID- 17434147
TI  - Molecular characterization of a novel RhoGAP, RRC-1 of the nematode
      Caenorhabditis elegans.
AB  - The GTPase-activating proteins for Rho family GTPases (RhoGAP) transduce diverse
      intracellular signals by negatively regulating Rho family GTPase-mediated
      pathways. In this study, we have cloned and characterized a novel RhoGAP for Rac1
      and Cdc42, termed RRC-1, from Caenorhabditis elegans. RRC-1 was highly homologous
      to mammalian p250GAP and promoted GTP hydrolysis of Rac1 and Cdc42 in cells. The
      rrc-1 mRNA was expressed in all life stages. Using an RRC-1::GFP fusion protein,
      we found that RRC-1 was localized to the coelomocytes, excretory cell, GLR cells,
      and uterine-seam cell in adult worms. These data contribute toward understanding
      the roles of Rho family GTPases in C. elegans.

PMID- 17434148
TI  - Signal-CF: a subsite-coupled and window-fusing approach for predicting signal
      peptides.
AB  - We have developed an automated method for predicting signal peptide sequences and
      their cleavage sites in eukaryotic and bacterial protein sequences. It is a 2
      layer predictor: the 1st-layer prediction engine is to identify a query protein
      as secretory or non-secretory; if it is secretory, the process will be
      automatically continued with the 2nd-layer prediction engine to further identify
      the cleavage site of its signal peptide. The new predictor is called Signal-CF,
      where C stands for "coupling" and F for "fusion", meaning that Signal-CF is
      formed by incorporating the subsite coupling effects along a protein sequence and
      by fusing the results derived from many width-different scaled windows through a
      voting system. Signal-CF is featured by high success prediction rates with short
      computational time, and hence is particularly useful for the analysis of large
      scale datasets. Signal-CF is freely available as a web-server at
      http://chou.med.harvard.edu/bioinf/Signal-CF/ or
      http://202.120.37.186/bioinf/Signal-CF/.

PMID- 17434150
TI  - Neuropeptides of Drosophila related to molluscan neuropeptides: dependence of the
      immunoreactivity pattern on the ontogenetic stage and functional state.
AB  - The CNP neuropeptides (Command Neuron Peptides) were first found in the command
      neurons for withdrawal behavior in the terrestrial snail. Given the fact that
      certain peptides can be found in various invertebrates, we examined Drosophila
      brains to determine if CNP-like peptides were present. Two types of antisera were
      used: one against CNP2, which was expected to recognize peptide products of the
      genes "hugin", "capa", CG6371, and a second antiserum against CNP4, which was
      expected to recognize neuropeptides encoded by the gene "capa" only. In larvae,
      both antibodies stained the abdominal perisympathetic organ, and several groups
      of neurons in the suboesophageal ganglia, while two neuronal clusters in the
      protocerebrum were stained with CNP2 antibody exclusively. The set of peptidergic
      neurons was conserved throughout all larval development. In the suboesophageal
      ganglia, the number of immunoreactive neurons apparently decreased at the pupae
      stage, and only one pair of large neurons in the caudal part of the
      suboesophageal ganglia was detected in adults. Experimental body injury led in
      the adult fruit flies to appearance of additional immunoreactive neurons, the
      pattern of staining becoming similar to that in larval CNS. The study
      demonstrates that the number of neurons expressing CNP-like immunoreactivity
      depends on the developmental stage and functional state of the animal, and that
      the CNP2-like and CNP4-like neuropeptides are colocalized in some neurons. We
      conclude that the family of CNP-like neuropeptides seems to be common for various
      invertebrate phyla.

PMID- 17434149
TI  - Regulation of CART mRNA by stress and corticosteroids in the hippocampus and
      amygdala.
AB  - CART (Cocaine-Amphetamine-Regulated Transcript) has been shown to be regulated by
      corticosteroids in the hypothalamus, but its regulation by corticosteroids and
      stress has not been well examined in the hippocampus or the amygdala. Further,
      CART has been implicated in the transition to puberty. In this study we examine
      the effects of acute (30 min) stress on CART mRNA in prepubescent and adult rats.
      In addition, we examined chronic (21 day x 6 h) restraint stress upon the
      expression of CART mRNA in the hippocampus and the amygdala and the effects of 7
      days of adrenalectomy and corticosteroid replacement upon CART expression in
      these regions of the adult rat brain. We found an up-regulation of CART mRNA in
      the central amygdala induced by acute but not chronic stress and an up-regulation
      in the dentate gyrus induced by chronic but not acute stress. Adrenalectomy
      reduced CART expression in the dentate gyrus but not the amygdala and this effect
      was blocked by corticosterone but not RU28,362 or aldosterone replacement,
      suggesting a synergism of mineralocorticoid and glucocorticoid receptors. Our
      data establish that CART expression is regulated by stress in a regionally and
      time specific manner and that CART is regulated by corticosteroid actions in the
      hippocampus.

PMID- 17434151
TI  - Pretreatment with volatile anesthetics, but not with the nonimmobilizer 1,2
      dichlorohexafluorocyclobutane, reduced cell injury in rat cerebellar slices after
      an in vitro simulated ischemia.
AB  - A prior exposure to the volatile anesthetic isoflurane has been shown to induce
      neuroprotection in rats. This phenomenon is called preconditioning. We designed
      this study to determine whether the potency of volatile anesthetics in inducing
      neuropreconditioning is related to their potency to induce anesthesia. Cerebellar
      slices of adult male Sprague-Dawley rats were exposed to various concentrations
      of isoflurane, halothane, sevoflurane, desflurane or the nonimmobilizer 1,2
      dichlorohexafluorocyclobutane for 15 min, followed by a 15-min drug-free period,
      and then were subjected to oxygen-glucose deprivation for 10 min at 37 degrees C.
      After a 5-h recovery at 37 degrees C, brain slices were used for quantification
      of cell injury by spectrophotometric measurement of formazan produced from 2,3,5
      triphenyltetrazolium chloride. All four volatile anesthetics induced a
      concentration-dependent preconditioning effect. The EC50 for this effect induced
      by isoflurane, halothane, sevoflurane or desflurane was 221, 173, 184 and 929
      microM, respectively. This EC50 was linearly correlated with the aqueous
      concentration of one minimum alveolar concentration. The volatile anesthetic
      preconditioning-induced neuroprotection was abolished by DL-threo-beta
      hydroxyaspartic acid, DL-threo-beta-benzyloxyaspartate or dihydrokainate,
      glutamate transporter inhibitors. The volatile nonimmobilizer 1,2
      dichlorohexafluorocyclobutane at any concentrations tested in the study did not
      induce a significant preconditioning effect. Isoflurane preconditioning did not
      change the oxygen-glucose deprivation-induced glutamate accumulation. These
      results suggest that the preconditioning-induced neuroprotection by volatile
      anesthetics is not agent-specific. Mechanisms that are involved in inducing
      anesthesia may contribute to the induction of preconditioning effect by volatile
      anesthetics. Modification of glutamate transporter activity may be one of such
      mechanisms to induce these protective effects.

PMID- 17434152
TI  - Early decrease of mitochondrial DNA repair enzymes in spinal motor neurons of
      presymptomatic transgenic mice carrying a mutant SOD1 gene.
AB  - Growing evidence has recently shown that mutant SOD1 accumulate in the
      mitochondria and cause vacuolation in transgenic mice carrying mutant SOD1, an
      animal model of amyotrophic lateral sclerosis (ALS). In this study, the
      expressions of DNA repair enzymes, oxoguanine glycosylase 1 (ogg1), DNA
      polymerase beta (polbeta), and DNA polymerase gamma (polgamma) were examined in
      transgenic mice with an ALS-linked mutant SOD1 gene, a valuable model for human
      ALS. In presymptomatic Tg mice, the nuclear form of ogg1 was upregulated, whereas
      mitochondrial ogg1 remained at the same level. DNA polymerase was selectively
      downregulated in the mitochondria. This study suggests an impaired protective
      mechanism against oxidative stress in mitochondria. The expressions of these
      enzymes are predominant in spinal motor neurons, suggesting a mechanism of
      selective motor neuron death in this animal model of ALS.

PMID- 17434153
TI  - Roles of programmed death-1 (PD-1)/PD-1 ligands pathway in the development of
      murine acute myocarditis caused by coxsackievirus B3.
AB  - OBJECTIVE: This study was designed to investigate the roles of programmed death-1
      (PD-1) and PD-1 ligands (PD-L) in the development of murine acute myocarditis
      caused by Coxsackievirus B3. PD-1/PD-L belong to the CD28/B7 superfamily, and the
      PD-1/PD-L pathway is known to transduce a negative immunoregulatory signal that
      antagonizes the T-cell receptor-CD28 signal and inhibits T-cell activation.
      METHODS: We first analyzed the expression of PD-L1/PD-L2 on cardiac myocytes in
      vivo and in vitro. Second, we examined the effects of in vivo treatment with an
      anti-PD-1, PD-L1, or PD-L2 monoclonal antibodies on the development of myocardial
      inflammation in C3H/He mice infected with Coxsackievirus B3. Third, to
      investigate the effects of anti-PD-1 monoclonal antibody treatment on the
      activation of the infiltrating cells, we examined the expression of interleukin
      (IL)-2, interferon (IFN)-gamma, CD40 ligand (CD40L), Fas ligand (FasL), and
      perforin as activation markers in mouse hearts by a semiquantitative PCR method.
      RESULTS: PD-L1 was markedly induced on cardiac myocytes with acute myocarditis.
      In vivo anti-PD-1 or -PD-L1 blocking monoclonal antibody treatment increased the
      myocardial inflammation whereas anti-PD-1 stimulating monoclonal antibody
      treatment decreased the myocardial inflammation, and anti-PD-L2 monoclonal
      antibody treatment had no effect. Anti-PD-1 monoclonal antibody treatment
      significantly increased the expression of IFN-gamma, FasL, CD40L, perforin, and
      Coxsackievirus B3 genomes in myocardial tissue. CONCLUSION: Our findings strongly
      suggest that the PD-1/PD-L1 pathway played a pivotal role in suppressing
      myocardial inflammation and raise the possibility of immunotherapy by stimulating
      the PD-1/PD-L1 pathway to prevent myocardial damage in viral myocarditis.

PMID- 17434154
TI  - A systematic bioinformatics approach for selection of epitope-based vaccine
      targets.
AB  - Epitope-based vaccines provide a new strategy for prophylactic and therapeutic
      application of pathogen-specific immunity. A critical requirement of this
      strategy is the identification and selection of T-cell epitopes that act as
      vaccine targets. This study describes current methodologies for the selection
      process, with dengue virus as a model system. A combination of publicly available
      bioinformatics algorithms and computational tools are used to screen and select
      antigen sequences as potential T-cell epitopes of supertype human leukocyte
      antigen (HLA) alleles. The selected sequences are tested for biological function
      by their activation of T-cells of HLA transgenic mice and of pathogen infected
      subjects. This approach provides an experimental basis for the design of pathogen
      specific, T-cell epitope-based vaccines that are targeted to majority of the
      genetic variants of the pathogen, and are effective for a broad range of
      differences in human leukocyte antigens among the global human population.

PMID- 17434156
TI  - Immunome: a reference set of genes and proteins for systems biology of the human
      immune system.
AB  - The function of the immune system requires coordinated expression and action of
      many genes and proteins. With the emergence of high throughput technologies it
      has become possible to target human immunity from a systems biology point of
      view. To perform systems biology studies with comparable results we need not just
      a reference gene and protein set but also useful and descriptive reference
      categories for the immunity related genes. We have identified and collected the
      genes and proteins of the essential human immunome. The 847 genes and proteins
      were annotated, and characterized, and they were categorized according to their
      functions, protein domains and Gene Ontology terms. The reference set and the
      categories are freely available in the immunome database at
      http://bioinf.uta.fi/Immunome/.

PMID- 17434155
TI  - The role of ABC-transporter gene polymorphisms in chemotherapy induced
      immunosuppression, a retrospective study in childhood acute lymphoblastic
      leukaemia.
AB  - We examined the association of functional ABCB1 (MDR1) and ABCG2 (BCRP)
      polymorphisms with acute side effects of chemotherapy. Analyses were performed on
      clinical data from 138 patients treated with the ALL-BFM-95 protocol implying
      several substrates of these transporters. ABCB1 3435T>C, 2677G>T/A 1236C>T and
      ABCG2 421C>A genotypes were determined. A higher proportion of ABCB1 3435TT
      patients suffered excessive infectious complications than those harbouring at
      least one C allele (OR=2.5, p=0.03) during the whole half-year-long intensive
      phase of chemotherapy. Weaker associations were calculated when ABCB1 1236T-2677T
      3435T haplotype homozygotes were tested against the remaining part of the
      population (OR=2.3, p=0.09). During the reinduction phase of therapy, the
      occurrence of severe leukocytopenia was similar among ABCB1 genotype groups. The
      frequency of any toxicities were not shown to differ according to the ABCG2
      421C>A genotype. Our data suggest that the ABCB1 3435T>C genotype is associated
      with the infectious complications of the applied chemotherapy regimen.

PMID- 17434157
TI  - Extending the Bacillus cereus group genomics to putative food-borne pathogens of
      different toxicity.
AB  - The Bacillus cereus group represents sporulating soil bacteria containing
      pathogenic strains which may cause diarrheic or emetic food poisoning outbreaks.
      Multiple locus sequence typing revealed a presence in natural samples of these
      bacteria of about 30 clonal complexes. Application of genomic methods to this
      group was however biased due to the major interest for representatives closely
      related to Bacillus anthracis. Albeit the most important food-borne pathogens
      were not yet defined, existing data indicate that they are scattered all over the
      phylogenetic tree. The preliminary analysis of the sequences of three genomes
      discussed in this paper narrows down the gaps in our knowledge of the B. cereus
      group. The strain NVH391-98 is a rare but particularly severe food-borne
      pathogen. Sequencing revealed that the strain should be a representative of a
      novel bacterial species, for which the name Bacillus cytotoxis or Bacillus
      cytotoxicus is proposed. This strain has a reduced genome size compared to other
      B. cereus group strains. Genome analysis revealed absence of sigma B factor and
      the presence of genes encoding diarrheic Nhe toxin, not detected earlier. The
      strain B. cereus F837/76 represents a clonal complex close to that of B.
      anthracis. Including F837/76, three such B. cereus strains had been sequenced.
      Alignment of genomes suggests that B. anthracis is their common ancestor. Since
      such strains often emerge from clinical cases, they merit a special attention.
      The third strain, KBAB4, is a typical facultative psychrophile generally found in
      soil. Phylogenic studies show that in nature it is the most active group in terms
      of gene exchange. Genomic sequence revealed high presence of extra-chromosomal
      genetic material (about 530kb) that may account for this phenomenon. Genes coding
      Nhe-like toxin were found on a big plasmid in this strain. This may indicate a
      potential mechanism of toxicity spread from the psychrophile strain community.
      The results of this genomic work and ecological compartments of different strains
      incite to consider a necessity of creating prophylactic vaccines against bacteria
      closely related to NVH391-98 and F837/76. Presumably developing of such vaccines
      can be based on the properties of non-pathogenic strains such as KBAB4 or
      ATCC14579 reported here or earlier. By comparing the protein coding genes of
      strains being sequenced in this project to others we estimate the shared
      proteome, or core genome, in the B. cereus group to be 3000+/-200 genes and the
      total proteome, or pan-genome, to be 20-25,000 genes.

PMID- 17434158
TI  - Error propagation in calculated ratios.
AB  - BACKGROUND: Calculated quantities that combine results of multiple laboratory
      tests have become popular for screening, risk evaluation, and ongoing care in
      medicine. Many of these are ratios. In this paper, we address the specific issue
      of propagated random analytical error in calculated ratios. METHODS: Standard
      error propagation theory is applied to develop an approximate formula for the
      mean, standard deviation (SD), and coefficient of variation (CV) of the ratio of
      two independent, normally distributed random variables. A method of
      mathematically modeling the problem by random simulations to validate these
      formulas is proposed and applied. Comparisons are made with the commonly quoted
      formula for the CV of a ratio. RESULTS: The approximation formula for the CV of a
      ratio R=X/Y of independent Gaussian random variables developed herein has an
      absolute percentage error less than 4% for CVs of less than 20% in Y. In contrast
      the commonly quoted formula has a percentage error of up to 16% for CVs of less
      than 20% in Y. CONCLUSION: The usual formula for the CV of a ratio functions well
      when the CV of the denominator is less than 10% but for larger CVs, the formula
      proposed here is more accurate. Random analytical error in calculated ratios may
      be larger than clinicians and laboratorians are aware. The magnitude of the
      propagated error needs to be considered when interpreting calculated ratios in
      the clinical laboratory, especially near medical decision limits where its effect
      may lead to erroneous conclusions.

PMID- 17434159
TI  - Diagnosis of breast cancer using Bayesian networks: a case study.
AB  - We evaluate the effectiveness of seven Bayesian network classifiers as potential
      tools for the diagnosis of breast cancer using two real-world databases
      containing fine-needle aspiration of the breast lesion cases collected by a
      single observer and multiple observers, respectively. The results show a certain
      ingredient of subjectivity implicitly contained in these data: we get an average
      accuracy of 93.04% for the former and 83.31% for the latter. These findings
      suggest that observers see different things when looking at the samples in the
      microscope; a situation that significantly diminishes the performance of these
      classifiers in diagnosing such a disease.

PMID- 17434160
TI  - Determining a continuous marker for sleep depth.
AB  - Detection and quantification of sleep arousals is an important issue, as the
      frequent arousals are known to reduce the quality of sleep and cause daytime
      sleepiness. In typical sleep staging, electroencephalograph (EEG) is the core
      signal and based on the visual inspection of the frequency content of EEG, non
      rapid eye movement sleep is staged into four somewhat rough categories. In this
      study, we aimed at developing a continuous marker based on a more rigorous
      spectral analysis of EEG to measure or quantify the depth of sleep. In order to
      develop such a marker, we obtained the time-frequency map of two EEG channels
      around sleep arousals and identified the frequency bands that show the most
      change during arousals. We then evaluated classification performance of the
      potential signals for representing the depth of sleep, using receiver operating
      characteristic analysis. Our comparisons based on the area under the curve values
      revealed that the sum of absolute powers in alpha and beta bands is a good
      continuous marker to represent the depth of sleep. Higher values of this marker
      indicate low-quality sleep and vice versa. We believe that use of this marker
      will lead to a better quantification of sleep quality.

PMID- 17434162
TI  - Reliability of spot test kits for detecting lead in household dust.
AB  - There has been a long-standing need for a technique that can provide fast,
      accurate and precise results regarding the presence of hazardous levels of lead
      in settled house dust. Several home testing kits are now available. One kit
      manufactured by Hybrivet (LeadCheck Swabs) is advertised as able to detect lead
      dust levels that exceed the US Environmental Protection Agency's dust lead
      standard for floors (40 microg/ft(2)). The purpose of the study was to determine
      the ability of LeadCheck Swabs to instantly detect lead in dust above EPA's
      hazard standard. A trained risk assessor collected 200 LeadCheck Swab samples
      side-by-side with standard dust wipe samples. The result of the LeadCheck Swab
      (positive (pink or red) or negative (yellow to brown)) was compared with the
      laboratory results for the corresponding dust wipe (over or under 40
      microg/ft(2)). The LeadCheck Swabs produced a false negative rate of 64% (95%
      confidence interval: 55%, 72%). The likelihood of a swab producing a false
      negative depended on substrate (painted or non-painted) and surface type (floor
      or sill). Changing the interpretation rule by classifying all swab colors except
      yellow as positive yielded lower false negative rates under some test conditions,
      but still produced high error rates. LeadCheck Swabs do not reliably detect
      levels of lead in dust above 40 microg/ft(2) using published methods under field
      conditions. Further research into alternate methodologies and interpretation
      guidance is needed to determine whether the swabs can be appropriately used by
      consumers and others to test homes for lead dust hazards.

PMID- 17434163
TI  - Frequent but nonrandom expression of myeloid markers on de novo childhood acute
      lymphoblastic leukemia.
AB  - The expression of the myeloid markers CD13, CD33, and CD15 in two hundred and
      eighty-three cases of de novo childhood acute lymphoblastic leukemia (ALL) is
      examined. The expression of at least one marker is a frequent event which is
      noted in 64% and 74% of B- and T-lineage ALL cases, respectively. Certain
      patterns of myeloid antigen expression can be recognized including: no expression
      of CD13, CD33, and CD15 in mature B-ALL, significantly higher levels of CD13 and
      CD33 and significantly lower levels of CD15 in TEL-AML1-positive B cell precursor
      ALL, no expression of CD13 and CD33 in E2A-PBX1-positive B cell precursor ALL
      cases and common T-ALL (double positive for CD4 and CD8), and no expression of
      CD13 in MLL-AF4-positive B cell precursor ALL cases. Although the numbers in some
      ALL subtypes are small, these patterns are consistent with nonrandom expression
      of myeloid markers in de novo childhood ALL.

PMID- 17434164
TI  - Regulation of the BRCA1 promoter in ovarian surface epithelial cells and ovarian
      carcinoma cells.
AB  - As BRCA1 expression is often suppressed in sporadic ovarian carcinoma we
      characterized the regulation of the 231nt proximal 'L6' fragment of the BRCA1
      promoter in two human ovarian surface epithelial cell and two sporadic ovarian
      carcinoma cell lines. Two individual regulatory elements within L6, the 'RIBS'
      element and the potential 'CRE' element were each necessary, but alone not
      sufficient for L6 activation in all four cell lines. The latter element showed
      some affinity for the CREB transcription factor, but cAMP pathway stimulation
      failed to promote its activation. This element did, however, interact with, and
      was activated by, c-Jun and Fra2 which suggests that it can interact with AP1
      like transcription factors and that it may act co-operatively with RIBS-binding
      factors to regulate BRCA1 transcription in ovarian cells.

PMID- 17434165
TI  - Molecular physiology of higher plant sucrose transporters.
AB  - Sucrose is the primary product of photosynthetic CO(2) fixation that is used for
      the distribution of assimilated carbon within higher plants. Its partitioning
      from the site of synthesis to different sites of storage, conversion into other
      storage compounds or metabolic degradation involves various steps of cell-to-cell
      movement and transport. Many of these steps occur within symplastic domains, i.e.
      sucrose moves passively cell-to-cell through plasmodesmata. Some essential steps,
      however, occur between symplastically isolated cells or tissues. In these cases,
      sucrose is transiently released into the apoplast and its cell-to-cell transport
      depends on the activity of plasma membrane-localized, energy dependent, H(+)
      symporting carrier proteins. This paper reviews the current knowledge of sucrose
      transporter physiology and molecular biology.

PMID- 17434166
TI  - The C-terminal sequence from common bugle leaf galactan:galactan
      galactosyltransferase is a non-sequence-specific vacuolar sorting determinant.
AB  - The Ajuga reptans L. galactan:galactan galactosyltransferase (ArGGT) is a
      vacuolar enzyme that synthesizes long-chain raffinose family oligosaccharides
      (RFOs), the major storage carbohydrates of this plant. ArGGT is structurally and
      functionally related to acid plant alpha-galactosidases (alpha-Gals) of the
      glycosylhydrolase family 27, present in the apoplast or the vacuole. Sequence
      comparison of acid alpha-Gals with ArGGT revealed that they all contain an N
      terminal signal sequence and a highly similar core sequence. Additionally, ArGGT
      and some acid alpha-Gals contain C-terminal extensions with low sequence
      similarities to each other. Here, we show that the C-terminal pentapeptide,
      SLQMS, is a non-sequence-specific vacuolar sorting determinant. Analogously, we
      demonstrate that the C-terminal extensions of selected acid alpha-Gals from
      Arabidopsis, barley, and rice, are also non-sequence-specific vacuolar sorting
      determinants, suggesting the presence of at least one vacuolar form of acid alpha
      Gal in every plant species.

PMID- 17434167
TI  - More than one door - Budding of enveloped viruses through cellular membranes.
AB  - Enveloped viruses exit their host cell by budding from a cellular membrane and
      thereby spread from one cell to another. Virus budding in general involves the
      distortion of a cellular membrane away from the cytoplasm, envelopment of the
      viral capsid by one or more lipid bilayers that are enriched in viral membrane
      glycoproteins, and a fission event that separates the enveloped virion from the
      cellular membrane. While it was initially thought that virus budding is always
      driven by viral transmembrane proteins interacting with the inner structural
      proteins, it is now clear that the driving force may be different depending on
      the virus. Research over the past years has shown that viral components
      specifically interact with host cell lipids and proteins, thereby adopting
      cellular functions and pathways to facilitate virus release. This review
      summarizes the current knowledge of the cellular membrane systems that serve as
      viral budding sites and of the viral and cellular factors involved in budding.
      One of the best studied cellular machineries required for virus egress is the
      ESCRT complex, which will be described in more detail.

PMID- 17434168
TI  - Juvenile hormone synthesis as related to egg development in neotenic
      reproductives of the termite Reticulitermes flavipes, with observations on urates
      in the fat body.
AB  - The relationship between juvenile hormone (JH) synthesis and egg development,
      which is well documented in cockroaches, is much less studied in their close
      relatives, the termites. In this study of neotenic reproductives of the
      subterranean termite Reticulitermes flavipes, in vitro rates of juvenile hormone
      (JH) synthesis by corpora allata (CA) are related to vitellogenic egg development
      and the size of CA. The first study compared brachypterous and apterous neotenics
      in their first cycle of egg development and a second study compared physogastric
      and non-physogastric brachypterous and apterous neotenics. In both studies, rates
      of JH synthesis correlated with the size of CA as indicated by their length.
      Unlike the cockroach in which all basal oocytes are in the same stage of
      development, those in termites are in various stages. In brachypterous and
      apterous in the first cycle of egg development, CA with high rates of JH
      synthesis were from females with early vitellogenic basal oocytes, whereas CA
      with low rates of JH synthesis were from females with either pre-vitellogenic or
      mature basal oocytes. This pattern of JH synthesis is similar to the cycle of JH
      synthesis correlated with oocyte development in several cockroach species. In
      later oocyte maturations, CA from physogastric apterous females with ovaries
      containing mature, as well as growing oocytes, showed a wide range of JH
      production; the CA with the highest rates of JH synthesis were from females with
      the highest proportion of early vitellogenic oocytes suggesting that both mature
      and early vitellogenic oocytes interact to regulate JH synthesis. Rates of JH
      synthesis were related to the number of vitellogenic ovarioles. Physogastric
      brachypterous neotenics, compared to the other classes of neotenic females, had
      CA with 2- to 4-fold higher rates of JH synthesis and ovaries with 2.5- to 8-fold
      greater number of vitellogenic ovarioles. However, both physogastric
      brachypterous and apterous neotenics had more vitellogenic basal oocytes and less
      urate in their fat bodies than the respective non-physogastric neotenics. These
      results demonstrate the similarities and differences between the classes of
      neotenic termites and between reproductive females in cockroaches and termites.

PMID- 17434169
TI  - The influence of ploidy on saltwater adaptation, acute stress response and immune
      function following seawater transfer in non-smolting rainbow trout.
AB  - We investigated the effect of ploidy on osmoregulatory, stress and immune
      responses in non-smolting rainbow trout during saltwater adaptation. Sibling
      groups of diploid and triploid trout were acclimated in freshwater (FW) and then
      subjected to abrupt transfer to full strength (35ppt) saltwater (SW) or back to
      FW. Fish were sampled pre-stress, and 1, 3, 6, 12, 24, 48, 72 and 168h post
      stress. Overall mortality in SW was less than 5% in either ploidy, with no
      mortality in FW. Significant elevations in plasma osmolality and gill ATPase were
      observed within 1-3h of SW transfer, but retuned to basal levels within 72h
      indicative of rapid saltwater adaptation and did not differ between ploidy.
      Furthermore, FW-SW transfer also caused significant and sustained elevations in
      total blood haemoglobin, plasma IGF-I, cortisol, glucose, total white blood cell
      counts, increased plasma but decreased mucus lysozyme, and enhanced head kidney
      macrophage respiratory burst activity. Conversely, FW-FW transfer evoked more
      transient and less elevated responses, more typical of primary and secondary
      responses to a single stressor. We conclude that the more elevated levels in
      these parameters are a function of saltwater adaptation as well as the generic
      stress response, and that this did not differ between ploidy. Strong positive
      correlations were found between plasma IGF-I and cortisol, and with osmolality,
      glucose and WBC, while a negative correlation was found with plasma lysozyme
      irrespective of ploidy. Overall, the current results suggest that triploidy does
      not affect the ability of non-smolting trout to adapt to full strength seawater
      under optimum conditions, and that the osmotic and stress response to such
      transfer is similar to diploids.

PMID- 17434170
TI  - The economic valuation of improved process plant decision support technology.
AB  - How can investments that would potentially improve a manufacturing plant's
      decision process be economically justified? What is the value of "better
      information," "more flexibility," or "improved integration" and the technologies
      that provide these effects? Technology investments such as improved process
      modelling, new real time historians and other databases, "smart" instrumentation,
      better data analysis and visualization software, and/or improved user interfaces
      often include these benefits as part of their valuation. How are these "soft"
      benefits to be converted to a quantitative economic return? Quantification is
      important if rational management decisions are to be made about the correct
      amount of money to invest in the technologies, and which technologies to choose
      among the many available ones. Modelling the plant operational decision cycle
      detect, analyse, forecast, choose and implement--provides a basis for this
      economic quantification. In this paper a new economic model is proposed for
      estimation of the value of decision support investments based on their effect
      upon the uncertainty in forecasting plant financial performance. This model leads
      to quantitative benefit estimates that have a realistic financial basis. An
      example is presented demonstrating the application of the method.

PMID- 17434171
TI  - The effect of high-dose aspirin pre-treatment on the incidence of myonecrosis
      following elective coronary stenting.
AB  - BACKGROUND: Inadequate platelet response to aspirin is associated with increased
      incidence of peri-procedural myonecrosis. Antiplatelet activity of aspirin can be
      improved by increasing the dose. High-dose aspirin pre-treatment, therefore, may
      reduce the incidence of myonecrosis post stenting. METHODS AND RESULTS: Two
      hundred patients taking 75-325 mg daily doses of aspirin for at least 2 weeks
      were randomized for addition or no addition of 500 mg aspirin before elective
      coronary stenting (aspirin 500 group, n=100 and control group, n=100). Primary
      endpoint was the occurrence of peri-procedural myonecrosis defined as creatine
      kinase-myocardial band (CK-MB) elevation of >1x upper limits of normal (ULN).
      Aspirin 500 patients were significantly younger and more likely to have family
      history of coronary artery disease, but less likely to have received statins than
      controls. Elevation of CK-MB was observed in 29% of aspirin 500 patients and 15%
      of controls (p=0.017). The incidence of non-Q wave myocardial infarction (CK-MB
      elevation of >3xULN) tended to be higher in the aspirin 500 group than in the
      control group (5% versus 0%, p=0.059). Multivariate analysis identified baseline
      aspirin dose (OR: 1.006; 95% CI: 1.002-1.010; p=0.004), aspirin 500 mg treatment
      (OR: 2.5; 95% CI: 1.2-5.5; p=0.021) and baseline CK-MB level (OR: 1.4; 95% CI:
      1.1-1.7; p=0.012) as independent predictors of CK-MB elevation after coronary
      stenting. CONCLUSION: For patients taking daily low-dose aspirin therapy,
      supplementation with high-dose aspirin before elective coronary stenting does not
      reduce, but may increase the incidence of peri-procedural myonecrosis.

PMID- 17434172
TI  - Subject-specific finite element models can accurately predict strain levels in
      long bones.
AB  - The prediction of the stress-state and fracture risk induced in bones by various
      loading conditions in individual patients using subject-specific finite element
      models still represents a challenge in orthopaedic biomechanics. The accuracy of
      the strain predictions reported in the literature is variable and generally not
      satisfactory. The aim of the present study was to evaluate if a proper choice of
      the density-elasticity relationship can lead to accurate strain predictions in
      the frame of an automatic subject-specific model generation strategy. To this
      aim, a combined numerical-experimental study was performed comparing finite
      element predicted strains with strain-gauges measurements obtained on eight
      cadaver proximal femurs, each instrumented with 15 rosettes mostly concentrated
      in the bone metaphyses, tested non-destructively in vitro under six different
      loading scenarios. Three different density-elasticity power relationships were
      selected from the literature and implemented in the finite element models derived
      from computed tomography data. The results of the present study confirm the great
      influence of the density-elasticity relationship used on the accuracy of
      numerical predictions. One of the tested constitutive laws provided a very good
      agreement (R(2)=0.91, RMSE lower than 10% of the maximum measured value) between
      numerical calculations and experimental measurements. The presented results show,
      in addition, that the adoption of a single density-elasticity relationship over
      the whole bone density range is adequate to obtain an accuracy that is already
      suitable for many applications.

PMID- 17434175
TI  - Simulation of droplet formation and coalescence using lattice Boltzmann-based
      single-phase model.
AB  - A lattice Boltzmann method-based single-phase free surface model is developed to
      study the interfacial dynamics of coalescence, droplet formation and detachment
      phenomena related to surface tension and wetting effects. Compared with the
      conventional multiphase models, the lattice Boltzmann-based single-phase model
      has a higher computational efficiency since it is not necessary to simulate the
      motion of the gas phase. A perturbation, which is given in the same fashion as
      the perturbation step in Gunstensen's color model, is added to the distribution
      functions of the interface cells for incorporating the surface tension into the
      single-phase model. The assignment of different mass gradients along the fluid
      wall interface is used to model the wetting properties of the solid surface.
      Implementations of the model are demonstrated for simulating the processes of the
      droplet coalescence, the droplet formation and detachment from ceiling and from
      nozzles with different shapes and different wall wetting properties.

PMID- 17434173
TI  - Characterization of apolipoprotein and apolipoprotein precursors in pancreatic
      cancer serum samples via two-dimensional liquid chromatography and mass
      spectrometry.
AB  - Major advances in cancer control depend upon early detection, early diagnosis and
      efficacious treatment modalities. Current existing markers of pancreatic ductal
      adenocarcinoma, generally incurable by available treatment modalities, are
      inadequate for early diagnosis or for distinguishing between pancreatic cancer
      and chronic pancreatitis. We have used a proteomic approach to identify proteins
      that are differentially expressed in sera from pancreatic cancer patients, as
      compared to control. Normal, chronic pancreatitis and pancreatic cancer serum
      samples were depleted of high molecular weight proteins by acetonitrile
      precipitation. Each sample was separated by chromatofocusing, and then further
      resolved by reversed-phase (RP)-HPLC. Effluent from the RP-HPLC column was split
      into two streams with one directly interfaced to an electrospray time-of-flight
      (ESI-TOF) mass spectrometer for molecular weight (MW) determination of the intact
      proteins. The remainder went through a UV detector with the corresponding peaks
      collected with a fraction collector, subsequently used for MS/MS analysis. The
      ion intensities of proteins with the same MW obtained from ESI-TOF-MS analysis
      were compared, with the differentially expressed proteins determined. An 8915 Da
      protein was found to be up-regulated while a 9422 Da protein was down-regulated
      in the pancreatic cancer sera. Both proteins were identified by MS and MS/MS as
      proapolipoprotein C-II and apolipoprotein C-III(1), respectively. The MS/MS data
      of proapolipoprotein C-II was searched using "semi-trypsin" as the search enzyme,
      thus confirming that the protein at 8915 Da was proapolipoprotein C-II. In order
      to confirm the identity of the protein at 9422 Da, we initially identified a
      protein of 8765 Da with a similar mass spectral pattern. Based on MS and MS/MS,
      its intact molecular weight and "semi-trypsin" database search, the protein at
      8765 Da was identified as apolipoprotein C-III(0). The MS and MS/MS data of the
      proteins at 8765 Da and 942 Da were similar, thus confirming the protein at 9422
      Da as being apolipoprotein C-III(1). The detection of differentially expressed
      proapolipoprotein C-II and apolipoprotein C-III(1) in the sera of pancreatic
      cancer patients may have utility for detection of this deadly malignancy.

PMID- 17434176
TI  - The interface engine: experimental consequences.
AB  - A light microscopy study confirms spontaneous emulsification at the quiescent,
      thermally equilibrated interface between pure oil and pure water during the
      chemical equilibration period. The process is qualitatively explained within the
      frame of the classical nucleation theory assuming a mixed interface layer between
      the two liquids in contact allowing supersaturation.

PMID- 17434177
TI  - Interaction forces between particles stabilized by a hydrophobically modified
      inulin surfactant.
AB  - The adsorption isotherm of a hydrophobically modified inulin (INUTEC SP1) on
      polystyrene (PS) and poly(methyl methacrylate) (PMMA) particles was determined.
      The results show a high affinity isotherm for both particles as expected for a
      polymeric surfactant adsorption. The interactions forces between two layers of
      the hydrophobically modified inulin surfactant adsorbed onto a glass sphere and
      plate was determined using a modified atomic force microscope (AFM) apparatus. In
      the absence of any polymer, the interaction was attractive although the energy of
      interaction was lower than predicted by the van der Waals forces. The results
      between two layers of the adsorbed polymer confirms the adsorption isotherms
      results and provides an explanation to the high stability of the particles
      covered by INUTEC SP1 at high electrolyte concentration. Stability of dispersions
      against strong flocculation could be attributed to the conformation of the
      polymeric surfactant at the solid/liquid interface (multipoint attachment with
      several loops) which remains efficient at Na(2)SO(4) concentration reaching 1.5
      mol dm(-3). The thickness of the adsorbed polymer layer in water determined both
      by AFM and rheology measurements, was found to be about 9 nm.

PMID- 17434178
TI  - ESR study of aqueous micellar solutions of perfluoropolyether surfactants with
      the use of fluorinated spin probes.
AB  - Fluoroalkyl esters of 3-carboxy pyrroline nitroxide, FPn (n=8 and 12), containing
      (n-2) CF(2) groups in the side-chain, were used as novel ESR spin probes of
      fluorinated micellar systems. The method was applied to study aqueous solutions
      of perfluoropolyether surfactants of the general formula
      Cl(C(3)F(6)O)(2)CF(2)COOX, consisting of two perfluoroisopropoxy units and the
      counterion X = Na(+) or NH(+)(4). By measuring the change of (14)N hyperfine
      splitting with surfactant concentration the critical micellar concentration of
      the ammonium salt was determined at temperatures of 297, 313 and 333 K. The ESR
      line shape was also examined as a function of surfactant concentration and of
      temperature in the range 120-360 K. The results are discussed in terms of
      solubilization and local environment of the probes in micelles of different size
      and shape, depending on the surfactant concentration and the kind of the
      counterion.

PMID- 17434179
TI  - Interfacial deposition of Ag on Au seeds leading to AucoreAgshell in organic
      media.
AB  - A seed mediated procedure for the synthesis of hydrophobic Au(core)Ag(shell)
      nanoparticles in toluene is demonstrated. The reaction proceeds by way of the
      interfacial reduction of silver ions by 3-pentadecylphenol followed by their
      deposition on hydrophobized Au nanoparticles. Such a hitherto unreported
      interfacial seeded growth reaction leads to the formation of phase pure
      Au(core)Ag(shell) nanoparticles that retain the hydrophobicity of the seed
      particles and remain stable in toluene. Such core-shell structures are however
      not formed in the aqueous phase. The core-shell architecture was verified using
      TEM analysis and the formation process was studied by recording the UV-vis
      spectra of the organic phase nanoparticles as a function of time. TEM kinetics
      also showed gradual increase in the silver layer thickness. Conclusive evidence
      was however obtained on examination of the HRTEM images of the products formed.
      Elemental analysis using X-ray photoelectron spectroscopy of the
      Au(core)Ag(shell) nanostructure revealed the presence of metallic silver.
      Moreover changing the surface capping of the Au seed does not affect the
      formation of the Au(core)Ag(shell) nanostructure.

PMID- 17434180
TI  - In situ Raman monitoring triazole formation from self-assembled monolayers of 1,4
      diethynylbenzene on Ag and Au surfaces via "click" cyclization.
AB  - We prepared acetylenyl-terminated aromatic self-assembled monolayers (SAMs) of
      1,4-diethynylbenzene on silver and gold. After the fabrication of pendent
      acetylenyl SAMs, the formation of triazoles was performed via Cu(I)-catalyzed
      Huisgen 1,3-dipolar cycloaddition "click" chemistry. A density functional theory
      (DFT) calculation of Raman frequencies showed good agreement with our
      experimental data to provide evidence of the formation of the triazole molecule.
      Our results indicated that "click" chemistry could be successfully applied to
      simple aromatic SAMs proximate (<1 nm) to roughened gold surfaces. The reaction
      process could be monitored in real time by measuring intensity changes of the
      nu(CC)(free) band in surface-enhanced Raman scattering (SERS) spectra.

PMID- 17434181
TI  - Thermodynamic studies of bovine lung surfactant extract mixing with cholesterol
      and its palmitate derivative.
AB  - Langmuir film behavior of bovine lipid extract surfactant (BLES), mixed with
      cholesterol (CHOL) and cholesterol palmitate (CHOLP), has been studied by surface
      pressure (pi)-area (A) measurements. Associative interactions, observed for both
      systems, were less favored at lower BLES content. The presence of unsaturated
      phospholipids and surfactant proteins in BLES favored the association.
      Miscibility of BLES was better with CHOLP than with CHOL at all compositions,
      indicating more compact packing of the BLES-CHOLP than of the BLES-CHOL system.
      The most stable mixtures were found at 30-40 mol% CHOL and at low pi and at 20-25
      mol% CHOLP but at higher pi. These results suggest that BLES-CHOL miscibility is
      better at low pi and low CHOL concentrations, while BLES-CHOLP miscibility is
      better at high pi and high CHOLP concentrations.

PMID- 17434182
TI  - Physiological changes leading to anhydrobiosis improve radiation tolerance in
      Polypedilum vanderplanki larvae.
AB  - High tolerance against various extreme environments exhibited by some
      anhydrobionts might be due to being almost completely desiccated, a state where
      little or no chemical reactions occur. We have shown that anhydrobiotic larvae of
      Polypedilum vanderplanki have higher tolerance against both high- and low-linear
      energy transfer (LET) radiation than hydrated larvae. It is of great interest to
      know how the desiccating larvae gain radiation tolerance. We therefore examined
      effects of high-LET radiation on four kinds of larvae: (1) normal hydrated
      (intact) larva, (2) intermediates between the anhydrobiotic and normal hydrated
      state, (3) almost completely dehydrated (anhydrobiotic) larvae, and (4)
      immediately rehydrated larvae that are assumed to have a similar molecular
      profile to anhydrobiotic larvae. The intermediates and immediately rehydrated
      larvae survived longer after high-LET radiation than intact larvae, indicating
      that radiation tolerance could be enhanced even in hydrated larvae. Physiological
      changes toward anhydrobiosis, e.g. accumulation of protectants or increasing
      damage repair capacity, correlate with improved radiation tolerance in hydrated
      larvae. In addition, almost complete desiccation further enhanced radiation
      tolerance, possibly in a different way from the hydrated larvae.

PMID- 17434184
TI  - Interaction between arthropod filiform hairs in a fluid environment.
AB  - Many arthropods use filiform hairs as mechanoreceptors to detect air motion. In
      common house crickets (Acheta domestica) the hairs cover two antenna-like
      appendages called cerci at the rear of the abdomen. The biomechanical stimulus
      response properties of individual filiform hairs have been investigated and
      modeled extensively in several earlier studies. However, only a few previous
      studies have considered viscosity-mediated coupling between pairs of hairs, and
      only in particular configurations. Here, we present a model capable of
      calculating hair-to-hair coupling in arbitrary configurations. We simulate the
      coupled motion of a small group of mechanosensory hairs on a cylindrical section
      of cercus. We have found that the coupling effects are non-negligible, and likely
      constrain the operational characteristics of the cercal sensory array.

PMID- 17434183
TI  - Comparison of fungal 80 S ribosomes by cryo-EM reveals diversity in structure and
      conformation of rRNA expansion segments.
AB  - Compared to the prokaryotic 70 S ribosome, the eukaryotic 80 S ribosome contains
      additional ribosomal proteins and extra segments of rRNA, referred to as rRNA
      expansion segments (ES). These eukaryotic-specific rRNA ES are mainly on the
      periphery of the 80 S ribosome, as revealed by cryo-electron microscopy (cryo-EM)
      studies, but their precise function is not known. To address the question of
      whether the rRNA ES are structurally conserved among 80 S ribosomes of different
      fungi we performed cryo-electron microscopy on 80 S ribosomes from the
      thermophilic fungus Thermomyces lanuginosus and compared it to the Saccharomyces
      cerevisiae 80 S ribosome. Our analysis reveals general structural conservation of
      the rRNA expansion segments but also changes in ES27 and ES7/39, as well as the
      absence of a tertiary interaction between ES3 and ES6 in T. lanuginosus. The
      differences provide a hint on the role of rRNA ES in regulating translation.
      Furthermore, we show that the stalk region and interactions with elongation
      factor 2 (eEF2) are different in T. lanuginosus, exhibiting a more extensive
      contact with domain I of eEF2.

PMID- 17434186
TI  - Considerations for the successful development and launch of personalised
      nutrigenomic foods.
AB  - The idea that diet and health are related is not new but the concept of direct
      nutrient-gene interactions is a new one for the food industry and the public to
      deal with. The ultimate goal of nutrigenomics is the development of foods that
      can be matched to individual human genotypes in order to benefit the health of
      those individuals. This paper discusses how personalised, nutrigenomic foods
      might be developed. Early results from research into food fractions that have the
      potential to ameliorate Crohn's disease are presented along with illustrations of
      candidate foods. Issues covering food customisation, consumer response and the
      ethics of genetic testing for food selection are also discussed briefly.

PMID- 17434185
TI  - Genetic disorders caused by mutated acetylcholine receptors.
AB  - The nicotinic acetylcholine receptors (nAChRs) are members of the large family of
      ligand-gated ion channels and are constituted by the assembly of five subunits
      arranged pseudosymmetrically around the central axis that forms a cation
      selective ion pore. They are widely distributed in both the nervous system and
      non-neuronal tissues, and can be activated by endogenous agonists such as
      acetylcholine or exogenous ligands such as nicotine. Mutations in neuronal nAChRs
      are found in a rare form of familial nocturnal frontal lobe epilepsy (ADNFLE),
      while mutations in the neuromuscular subtype of the nAChR are responsible for
      either congenital myasthenia syndromes (adult subtype of neuromuscular nAChR) or
      a form of arthrogryposis multiplex congenita type Escobar (fetal subtype of
      neuromuscular nAChR).

PMID- 17434187
TI  - Assessment of atypical DNA intercalating agents in biological and in silico
      systems.
AB  - Non-covalent genotoxic interaction between DNA and classical planar fused-ring
      intercalating agents, has been well understood for some time especially in the
      context of frameshift mutagenesis in bacterial systems. Recent evidence, however,
      suggests that a rather wide structural range of small non-fused ring molecules
      may also be capable of partial or complete DNA intercalation in mammalian cells.
      The present paper will review recent studies on the identification and
      characterization of such atypically-structured molecules utilizing both cell
      based and three-dimensional computational analyses focusing principally on
      prediction and detection of these atypical molecules. Mechanistic aspects of
      genotoxicity of such non-covalent binding molecules, with emphasis on marketed
      pharmaceuticals, will also be discussed. A review and presentation of new data
      using catalytic DNA topo II inhibitors, confirms the notion that topoisomerase II
      poisoning arising via intercalation is the major mechanism of genotoxicity of
      these drugs.

PMID- 17434188
TI  - Effects of environmental air pollution on endogenous oxidative DNA damage in
      humans.
AB  - Epidemiological studies conducted in metropolitan areas have demonstrated that
      exposure to environmental air pollution is associated with increases in
      mortality. Carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) are the major
      source of genotoxic activities of organic mixtures associated with respirable
      particulate matter, which is a constituent of environmental air pollution. In
      this study,we wanted to evaluate the relationship between exposure to these
      genotoxic compounds present in the air and endogenous oxidative DNA damage in
      three different human populations exposed to varying levels of environmental air
      pollution. As measures of oxidative DNA damage we have determined 8-oxo-7,8
      dihydro-2'-deoxyguanosine (8-oxodG) by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) and cyclic pyrimidopurinone N-1,N(2) malondialdehyde-2'
      deoxyguanosine (M(1)dG) by the immunoslot blot assay from lymphocyte DNA of
      participating individuals. The level of endogenous oxidative DNA damage was
      significantly increased in individuals exposed to environmental air pollution
      compared to unexposed individuals from Kosice (8-oxodG adducts) and Sofia (M(1)dG
      adducts). However, there was no significant difference in the level of endogenous
      oxidative DNA and exposure to environmental air pollution in individuals from
      Prague (8-oxodG and M(1)dG adducts) and Kosice (M(1)dG adducts). The average
      level of M(1)dG adducts was significantly lower in unexposed and exposed
      individuals from Kosice compared to those from Prague and Sofia. The average
      level of 8-oxodG adducts was significantly higher in unexposed and exposed
      individuals from Kosice compared to those from Prague. A significant increasing
      trend according to the interaction of c-PAHs exposure and smoking status was
      observed in levels of 8-oxodG adducts in individuals from Kosice. However, no
      other relationship was observed for M(1)dG and 8-oxodG adduct levels with regard
      to the smoking status and c-PAH exposure status of the individuals. The
      conclusion that can be made from this study is that environmental air pollution
      may alter the endogenous oxidative DNA damage levels in humans but the effect
      appears to be related to the country where the individuals reside. Genetic
      polymorphisms of the genes involved in metabolism and detoxification and also
      differences in the DNA repair capacity and antioxidant status of the individuals
      could be possible explanations for the variation observed in the level of
      endogenous oxidative DNA damage for the different populations.

PMID- 17434189
TI  - alpha-Glucosidase inhibitory constituents from stem bark of Terminalia superba
      (Combretaceae).
AB  - The CH(2)Cl(2)/CH(3)OH (1/1) extract of the dried stem bark of Terminalia superba
      afforded two compounds, (7S,8R,7'R,8'S)-4'-hydroxy-4-methoxy-7,7'-epoxylignan and
      meso-(rel 7S,8R,7'R,8'S)-4,4'-dimethoxy-7,7'-epoxylignan along with 11 known
      compounds. The structures of the compounds were established by analysing the
      spectroscopic data and also comparing it with the data of previously known
      analogues. All the isolated compounds were evaluated for their glycosidase
      inhibition activities. Gallic acid and methyl gallate showed significant alpha
      glucosidase inhibition activity.

PMID- 17434190
TI  - Isoflavanones and their O-glycosides from Desmodium styracifolium.
AB  - Two isoflavanones (5,7-dihydroxy-2',3',4'-trimethoxy-isoflavanone and 5,7
      dihydroxy-2'-methoxy-3',4'-methylenedioxy-isoflavanone), four isoflavanone O
      glycosides (5,7-dihydroxy-2',3',4'-trimethoxy-isoflavanone 7-O-beta
      glucopyranoside, 5,7-dihydroxy-2'-methoxy-3',4'-methylenedioxy-isoflavanone 7-O
      beta-glucopyranoside, 5,7-dihydroxy-2',4'-dimethoxy-isoflavanone 7-O-beta
      glucopyranoside, and 5,7,4'-trihydroxy-2',3'-dimethoxy-isoflavanone 7-O-beta
      glucopyranoside), and a coumaronochromone (3,5,7,4'-tetrahydroxy
      coumaronochromone), along with 25 known compounds, were isolated from the aerial
      parts of Desmodium styracifolium. This is for the first time isoflavanone O
      glycosides were isolated from a natural source.

PMID- 17434191
TI  - Taxonomic, genetic, chemical and estrogenic characteristics of Epimedium species.
AB  - To understand the factors contributing to estrogenic properties of extracts from
      the genus Epimedium L. (Berberidaceae), we performed taxonomic, genetic and
      chemical characterization on 37 specimens from 18 species and related these to
      estrogen receptor (ERalpha and ERbeta) bioactivity, as measured by reporter genes
      in stable human cells. Boot strap values derived from amplified fragment length
      polymorphisms indicated that specimens of E. koreanum, E. brevicornum, E.
      myrianthum, E. leishanense, and E. membranaceum were genetically distinct and
      this was supported by their very similar ERalpha activities. In contrast,
      specimens from E. pubescens and E. sagittatum were diverse both genetically,
      chemically and in terms of ERalpha and ERbeta bioactivities. Strikingly, a
      genetic cluster comprising six rare Epimedium species exhibited strongest ERalpha
      and ERbeta activity, and this bioactivity was positively correlated with content
      of trace flavonoid aglycones (kaempferol, apigenin, quercetin, luteolin and
      breviflavone B). In contrast, there was no association between estrogenic
      activity and the major flavonol glycoside constituents (icariin and epimedin A
      C). Although they exhibited equally strong ERalpha and ERbeta activity, E.
      koreanum can be clearly differentiated from E. pubescens and E. brevicornum by
      genetic distance and its significantly lower content of epimedin C. Our
      morphologic, genetic, chemical and bioactivity profiling provide the basis for
      the production of extracts with reproducible estrogenic properties. Such
      reproducibility will be critical for the standardization of Epimedium-based
      products.

PMID- 17434192
TI  - The synthesis and enzymic hydrolysis of (E)-2-[2,3-2H2]propenyl glucosinolate:
      confirmation of the rearrangement of the thiohydroximate moiety.
AB  - (E)-2-[2,3-2H2]propenyl glucosinolate was synthesised starting from (E)-[3,4
      2H2]but-3-en-1-ol, which was produced by reduction of but-3-yn-1-ol with
      deuterium gas in the presence of Lindlar's catalyst. The synthesis of (E)-2-[2,3
      2H2]propenyl glucosinolate was completed via the nitro intermediate to form the
      basic desulphoglucosinolate skeleton. The (E)-2-[2,3-2H2]propenyl glucosinolate
      was fully characterised and deuterium NMR spectroscopy used to examine the
      rearrangement of the thiohydroximate to the isothiocyanate and thiocyanate.

PMID- 17434193
TI  - Retrospective study of bacterial isolates and their antimicrobial
      susceptibilities in equine uteri during fertility problems.
AB  - Bacterial pathogens are a potential cause when a mare fails to conceive to a
      fertile stallion on a well-managed breeding farm on one or more cycles in the
      same season. Furthermore, emerging bacterial resistance to commonly used
      (topical) antibiotics has been demonstrated. In this study, a total of 586
      uterine swabs from mares with fertility problems were evaluated and the bacterial
      isolates were identified and measured for resistance to 10 antibiotics most
      commonly used during bacterial equine infection. Forty-nine percent of the
      examined mares were positive at bacteriological investigations. Amongst 347
      successful isolations, 31.7% were Streptococcus group C and 18.4% Escherichia
      (E.) coli, both considered frequently associated with fertility problems.
      Determination of the antibiotic susceptibility pattern of Streptococcus group C
      (110 organisms) revealed that only the amoxicillin/clavulanic acid was highly
      active with 82.7% of the isolates being inhibited. For E. coli, a major number of
      drugs displayed a high potency.

PMID- 17434194
TI  - ESAT-6 and CFP-10 can be combined to reduce the cost of testing for Mycobacterium
      tuberculosis infection, but CFP-10 responses associate with active disease.
AB  - Commercial tests measuring IFN-gamma responses to ESAT-6 and CFP-10 are available
      for diagnosing Mycobacterium tuberculosis infection. Measures that minimize cost
      and complexity will facilitate their application in less-developed countries. We
      investigated whether overlapping peptides representing both ESAT-6 and CFP-10 are
      required to detect M. tuberculosis infection in a high TB-burden country, and
      whether they can be combined in a single pool. ESAT-6 and CFP-10 peptides were
      compared in IFN-gamma enzyme-linked immunospot (ELISPOT) in 183 HIV-negative
      smear-positive TB cases and 1673 HIV-negative household contacts. Separate
      peptide pools for each antigen were compared with a combined pool in 498
      contacts. Forty per cent of responsive contacts recognized both antigens, 51%
      only ESAT-6 and 10% only CFP-10, whereas 56% of responsive cases recognized both
      antigens, 30% only ESAT-6 and 13% only CFP-10. Accordingly, CFP-10 response rates
      were higher for TB cases (odds ratio 2.409, P<0.001). Low purified protein
      derivative response rates indicated that responses to CFP-10 only were non
      specific in contacts. Agreement between peptides in separate versus combined
      pools was good (kappa=0.758, r=0.840). Therefore a combined ESAT-6/CFP-10 peptide
      pool provided maximum sensitivity and efficiency, but CFP-10 was mainly required
      to detect active disease.

PMID- 17434196
TI  - Ultrastructural aspects of the 'statocyst' of Xenoturbella (Deuterostomia) cast
      doubt on its function as a georeceptor.
AB  - The "statocyst" in the enigmatic worm Xenoturbella is a structure containing
      motile flagellated cells. It is situated inside the subepidermal membrane complex
      (between epidermis and muscular layers) in the anterior end of the body. The
      motile cells contain a lipophilic refractile body ("statolith"), and a series of
      vesicles from small dense core vesicles presumably formed from the refractile
      body to large vesicles with dense aggregates of filamentous tubules that become
      exocytized through secretion. It is unlikely that the statocyst is a georeceptor
      (true statocyst); maybe it has an endocrine function.

PMID- 17434195
TI  - The treatment of severe malaria.
AB  - In the SEAQUAMAT trial, parenteral artesunate was shown to be associated with a
      considerably lower mortality than quinine, and is now the recommended treatment
      for severe malaria in low-transmission areas and in the second and third
      trimesters of pregnancy. A trial is underway to establish its role in African
      children. The development of artesunate suppositories may provide the means to
      treat patients with severe disease in remote rural settings, potentially buying
      the time needed to reach a health care facility. The increasing availability of
      basic intensive care facilities in developing countries also has the potential to
      further reduce mortality.

PMID- 17434197
TI  - Antioxidative stress response of Lepidium sativum due to exposure to
      cyanobacterial secondary metabolites.
AB  - Agricultural plants can come in contact with cyanobacterial toxins via spray
      irrigation techniques. After uptake in the plants, cyanobacterial toxins are able
      to induce oxidative stress via the enhanced production of reactive oxygen
      species. If the initiated oxidation processes proceeds uninhibited, extensive
      cellular damage might occur like DNA damage, protein inhibition or lipid
      peroxidation. The results provide further evidence that cyanobacterial toxins as
      well as cyanobacterial crude extract containing microcystins-LR induce oxidative
      stress response in Lepidium sativum seedlings, manifested by lipid peroxidation,
      elevation of alpha- and beta-tocopherol concentrations and elevated activities of
      antioxidative enzymes like the glutathione peroxidase, glutathione S-transferase
      and glutathione reductase.

PMID- 17434198
TI  - An ultra-performance liquid chromatography-tandem mass spectrometry method for
      determination of microcystins occurrence in surface water in Zhejiang Province,
      China.
AB  - A novel method had been developed for determination of microcystin in surface
      water by ultra-performance liquid chromatography combined with tandem mass
      spectrometry (UPLC-MS/MS). Water samples after being concentrated and cleaned
      with solid phase extraction (SPE) with Oasis HLB cartridge were separated on
      AcQuity UPLC BEH C18 column (1.7 microm, 1.0 x 50 mm) with a gradient elution and
      a mobile phase consisting of 0.1% formic acid in water and methanol, and then
      detected with an electrospray ionization tandem mass spectrometry in positive ion
      mode with multiple reaction monitoring. Compared with traditional liquid
      chromatography, it took much less time for UPLC to analyze microcystin.
      Additionally, the UPLC-MS/MS method produced satisfactory reliability,
      sensitivity, and accuracy. Recoveries of the four microcystins were 91.7-111%
      with relative standard deviation being 7.9-12%. The calibration curves for
      microcystins were linear with correlation coefficient being larger than 0.99.
      Limit of quantification of the four microcystins (microcystin-LR, RR, LW, and LF)
      after 1000-fold SPE pre-concentration, were 2.5, 6.0, 2.5, and 1.3 ng/L. The
      presented method had been successfully used to detect microcystin in surface
      water from the Qiantang River, the West Lake, and three drinking water
      reservoirs, which represented water bodies of river, lake, and drinking water
      reservoir, respectively. It was shown that microcystin pollution in drinking
      water reservoirs was the heaviest, and microcystin-LR and RR were the predominant
      kinds, with concentrations ranging 0.045-2.73 and 0.021-1.36 microg/L,
      respectively. The concentrations of microcystins in river and lake were all under
      detection limit.

PMID- 17434199
TI  - Neurokinin-1 enables measles virus trans-synaptic spread in neurons.
AB  - Measles virus (MV), a morbillivirus that remains a significant human pathogen,
      can infect the central nervous system, resulting in rare but often fatal
      diseases, such as subacute sclerosing panencephalitis. Previous work demonstrated
      that MV was transmitted trans-synaptically and that, while a cellular receptor
      for the hemagglutinin (H) protein was required for MV entry, it was dispensable
      for subsequent cell-to-cell spread. Here, we explored what role the other
      envelope protein, fusion (F), played in trans-synaptic transport. We made the
      following observations: (1) MV-F expression in infected neurons was similar to
      that seen in infected fibroblasts; (2) fusion inhibitory peptide (FIP), an
      inhibitor of MV fusion, prevented both infection and spread in primary neurons;
      (3) Substance P, a neurotransmitter with the same active site as FIP, also
      blocked neuronal MV spread; and (4) both genetic deletion and pharmacological
      inhibition of the Substance P receptor, neurokinin-1 (NK-1), reduced infection of
      susceptible mice. Together, these data implicate a role for NK-1 in MV CNS
      infection and spread, perhaps serving as an MV-F receptor or co-receptor on
      neurons.

PMID- 17434200
TI  - Treatment of landfill leachate by combined aged-refuse bioreactor and electro
      oxidation.
AB  - Two-stage aged-refuse bioreactor (ARB) was applied to treat landfill leachate in
      Shanghai Waste Laogang Disposal Plant. The removal efficiencies of chemical
      oxygen demand (COD), biological oxygen demand (BOD), total organic carbon (TOC),
      total nitrogen (TN) and ammonia nitrogen (NH(3)-N) of landfill leachate treated
      by the two-stage bioreactor system were 98.5%, 99.9%, 98.0%, 64.2% and 99.9%,
      respectively. The COD and BOD in the second stage effluent were 239 and 7 mg l(
      1), respectively. Thus three types of electrolysis were employed to further treat
      the second effluent, undivided electrolysis (UDE), divided electrolysis (DE) with
      Ti/PbO(2) cathode and DE with gas diffusion cathode. All electrolysis processes
      possessed good color removal effect, while the DE with gas diffusion cathode had
      the best TOC removal effect. The optimum electrolysis time of leachate was 30
      min. The TOC removal efficiencies were 51.4% and 39.7% in anolyte and catholyte,
      respectively, after 30 min electrolysis at 5 V. In addition, the DE with gas
      diffusion cathode showed the least energy consumption of 9.8 k Whm(-3) at 30 min.
      The organic pollutants in the leachate were analyzed through a gas chromatography
      coupled with mass spectrometry (GC-MS) system. Through the two-stage ARB, the
      species and concentrations of organic pollutants in landfill leachate reduced
      greatly. Several chlorinated organic compounds were detected in the effluent
      after the UDE and the anolyte of the DE. In addition, the concentration of
      absorbable organic halogens (AOX) increased greatly during the electrolysis.
      Hence, careful consideration should be given in the application of electro
      oxidation into the treatment of chloride-containing wastewater.

PMID- 17434201
TI  - Optimization of anaerobic acidogenesis of an aquatic plant, Canna indica L., by
      rumen cultures.
AB  - Anaerobic acidogenesis of Canna indica L. (canna) by rumen cultures was
      investigated in this study. Fractional factorial design (FFD) was used to explore
      the roles of the growth factors such as substrate concentration and pH in such a
      bioconversion, whereas response surface methodology (RSM) was employed for
      optimizing this acidogenic process. The optimum substrate concentration and pH
      for the acidogenesis of canna were found to be 8.2 g VSl(-1) and 6.6,
      respectively, and the corresponding degradation efficiency of canna was 52.3%.
      Volatile fatty acid yield peaked at 0.362 g g(-1)VS degraded at a substrate
      concentration of 6.9 g VSl(-1)and pH 6.7. These results were confirmed by the
      experimental results.

PMID- 17434202
TI  - Removal of the endocrine disrupter nonylphenol and its estrogenic activity in
      sludge treatment processes.
AB  - The estrogenic compound nonylphenol (NP) is frequently found in sludge from
      sewage treatment works. Hence, when sewage sludge is spread on the land,
      endocrine-disrupting compounds may get into the soil. The goal of this study was
      to investigate the extent to which aerobic mesophilic treatment in continuous
      reactors permits the removal of NP from sludge and how this process may be useful
      for treating anaerobically stabilised sludge. We also report on the behaviour of
      NP during the anaerobic treatment of sludge. The reduction in sludge estrogenic
      activity observed in the different types of treatment, as measured using estrogen
      responsive reporter cells lines (MELN bioassay), was compared with NP removal
      rates. Under anaerobic conditions, no degradation of NP and its estrogenic
      activity was observed. Indeed, an accumulation of the compound occurred. In
      contrast, high removal of NP was achieved in aerobic conditions as well as in
      aerobic Post-treatment of anaerobically pre-digested sludge, with a concomitant
      reduction of the sludge's estrogenic potency.

PMID- 17434203
TI  - Effect of COD/SO(4)(2-) ratio and sulfide on thermophilic (55 degrees C) sulfate
      reduction during the acidification of sucrose at pH 6.
AB  - This study investigated the effect of the COD/SO(4)(2-) ratio (4 and 1) and the
      sulfide concentration on the performance of thermophilic (55 degrees C)
      acidifying (pH 6) upflow anaerobic sludge bed reactors fed with sucrose at an
      organic loading rate of 4.5 g COD l(reactor)(-1)day(-1). Sulfate reduction
      efficiencies amounted to 65% and 25-35% for the COD/SO(4)(2-) ratios of 4 and 1,
      respectively. Acidification was complete at all the tested conditions and the
      electron flow was similar at the two COD/SO(4)(2-) ratios applied. The stepwise
      decrease of the sulfide concentrations in the reactors with a COD/SO(4)(2-) ratio
      of 1 by N(2) stripping caused an immediate stepwise increase in the sulfate
      reduction efficiencies, indicating a reversible inhibition by sulfide. The degree
      of reversibility was, however, affected by the growth conditions of the sludge.
      Acidifying sludge pre-grown at pH 6, at a COD/SO(4)(2-) ratio of 9 and exposed
      for 150 days to 115 mg l(-1) sulfide, showed a slower recovery from the sulfide
      inhibition than a freshly harvested sludge from a full scale treatment plant (pH
      7 and COD/SO(4)(2-)=9.5) exposed for a 70 days to 200 mg l(-1) sulfide. In the
      latter case, the decrease of the sulfide concentration from 200 to 45 mg l(-1)
      (35 mg l(-1) undissociated sulfide) by N(2) stripping caused an immediate
      increase of the sulfate reduction efficiency from 35% to 96%.

PMID- 17434204
TI  - Microbial processes associated to the decontamination and detoxification of a
      polluted activated sludge during its anaerobic stabilization.
AB  - Xenobiotic compounds accumulate in activated sludge resulting from wastewater
      treatment plants serving both civil and industrial areas. The opportunity to use
      anaerobic digestion for the decontamination and beneficial disposal of a
      contaminated activated sludge was investigated in mesophilic and thermophilic
      microcosms monitored through an integrated chemical, microbiological and
      ecotoxicological procedure. The 10 months anaerobic sludge incubation at 35
      degrees C resulted in an extensive production of a methane-rich biogas, a marked
      reduction of pathogenic cultivable bacteria and, importantly, a marked
      biodegradation of the sludge-carried organic pollutants, including some
      polychlorinated biphenyls and polycyclic aromatic hydrocarbons, along with a
      relevant sludge detoxification. The sludge decontamination seemed to occur mostly
      under methanogenic conditions and was not significantly affected by the addition
      of yeast extract or molasses. Lower bioremediation and biomethanization yields
      were observed under thermophilic conditions.

PMID- 17434205
TI  - A transition state analog for phosphate diester cleavage catalyzed by a small
      enzyme-like metal ion complex.
AB  - The values of K(i) for methylphosphate dianion (MP(2-)) inhibition of the
      cleavage of 2-hydroxypropyl-4-nitrophenyl phosphate (HpPNP) catalyzed by 1,3
      bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn(2)(1)(H(2)O)) approach a
      small limiting value of 6 microM at pH<pK(a)=7.8 for deprotonation of the
      catalyst to form Zn(2)(1)(HO(-)). There is a 1600-fold difference in the affinity
      of a phosphate diester monoanion (diethylphosphate) and phosphate monester
      dianion (MP(2-)) for Zn(2)(1)(H(2)O). This suggests that the latter is an analog
      for the transition state dianion for the cleavage reaction of HpPNP and other
      phosphate diesters. The observation that this transition state analog binds
      selectively to Zn(2)(1)(H(2)O) provides strong evidence that this is the active
      form of the catalyst which binds selectively to the ionized substrate. The
      efficiency of catalysis of the cleavage of phosphate diesters by Zn(2)(1)(H(2)O)
      and proteins is compared.

PMID- 17434206
TI  - Arsenic in the environment: Biology and Chemistry.
AB  - Arsenic (As) distribution and toxicology in the environment is a serious issue,
      with millions of individuals worldwide being affected by As toxicosis. Sources of
      As contamination are both natural and anthropogenic and the scale of
      contamination ranges from local to regional. There are many areas of research
      that are being actively pursued to address the As contamination problem. These
      include new methods of screening for As in the field, determining the
      epidemiology of As in humans, and identifying the risk of As uptake in
      agriculture. Remediation of As-affected water supplies is important and research
      includes assessing natural remediation potential as well as phytoremediation.
      Another area of active research is on the microbially mediated biogeochemical
      interactions of As in the environment. In 2005, a conference was convened to
      bring together scientists involved in many of the different areas of As research.
      In this paper, we present a synthesis of the As issues in the light of long
      standing research and with regards to the new findings presented at this
      conference. This contribution provides a backdrop to the issues raised at the
      conference together with an overview of contemporary and historical issues of As
      contamination and health impacts.

PMID- 17434207
TI  - Adjustments on the cryopreservation conditions reduce the incidence of boar
      ejaculates with poor sperm freezability.
AB  - The objective of the present study was to evaluate the effectiveness of different
      cryopreservation conditions (CCs) for freezing and thawing boar ejaculates,
      focusing on those having sub-optimal sperm freezability. Using a split-ejaculate
      technique, single ejaculates from 53 boars were diluted in lactose-egg yolk
      extender, containing a final glycerol concentration (GLY) of 2 or 3%, packaged in
      0.5 mL straws and were cooled at rates of -10, -40 or -60 degrees C/min (cooling
      rate: CR). Thereafter, the frozen sperm samples were thawed by warming them at
      rates of approximately 1200 or approximately 1800 degrees C/min (warming rate:
      WR). Frozen-thawed sperm samples were assessed for the sperm motility (CASA
      system) and flow cytometric analysis of plasma and acrosomal membranes integrity.
      Cooling rate had no influence (P>0.05) on sperm quality parameters, however GLY
      and WR independently affected (P<0.05) all assessed sperm parameters. Evaluating
      the combined effect of GLY and WR (four different CCs resulting of a 2 x 2
      factorial design), the best post-thaw quality results were achieved for sperm
      samples frozen with 3% glycerol and thawed at 1800 degrees C/min (CC4). However,
      there was a significant interaction (P<0.001) between CC and ejaculate for all
      post-thaw sperm quality assessments. Therefore, ejaculates were classified in
      three different populations according to the post-thaw sperm quality achieved
      using control CC (CC1: 2% of glycerol and approximately 1200 degrees C/min of
      warming). The effectiveness of CCs was different (P<0.05) in the three ejaculate
      populations. Spermatozoa from ejaculates considered as "good" freezers were
      relatively unaffected (P>0.05) by the modifications in the CCs, whereas those
      from "moderate" and, mainly, "bad" freezers were very sensitive (P<0.05). In
      conclusion, optimization of the CCs - GLY and WR - can improve the cryosurvival
      of spermatozoa in some ejaculates, particularly in those having poor sperm
      freezing ability.

PMID- 17434208
TI  - Novel transcriptional regulation of the schlafen-2 gene in macrophages in
      response to TLR-triggered stimulation.
AB  - Schlafen-2 (slfn-2) is a member of slfn family, regulators of T cell development
      and its expression is altered during infection by microbial pathogens. However,
      the molecular mechanism involved in slfn expression is still to be determined. In
      this study, we isolated slfn-2 as a LPS-induced differentially expressed genes
      (DEGs) in RAW 264.7 cells and examined expression and regulation of slfn-2 in CpG
      DNA-treated and LPS-treated macrophages. We defined a transcriptional start site
      in the slfn-2 gene. To examine the promoter organization of the slfn-2 gene, we
      cloned a approximately 1.8 kb region upstream of the transcription start site.
      Sequence analysis indicates consensus sites for AP-1 and NF-kappaB. Comprehensive
      mutant analyses, ELISA-based transcription factor activation assay, and ChIP
      assays reveal that functional interaction of AP-1 and NF-kappaB with the promoter
      element is necessary for the Toll-like receptor (TLR)-mediated slfn-2 gene
      expression by CpG-DNA and LPS treatment in macrophages. In summary, we identified
      a slfn-2 promoter for the first time and demonstrated that CpG-DNA and LPS
      triggers slfn-2 gene expression by activating NF-kappaB and AP-1 pathways in
      macrophages.

PMID- 17434209
TI  - Immunosuppressive effect of pregnant mouse serum on allostimulatory activity of
      dendritic cells.
AB  - In normal pregnancy, the maternal immune system is directed towards tolerance or
      suppression in order to prevent rejection of the semi-allogenic fetus. Antigen
      presenting cells, especially dendritic cells (DCs), are key cells in initiation
      and regulation of immune responses. The presence of potent immunostimulatory DCs
      in the decidual tissue of pregnancy has been demonstrated. The aim of this study
      was to determine how allostimulatory activity of DCs could be affected during
      pregnancy. DCs were isolated from spleen of pregnant or non-pregnant Balb/c mice
      and co-cultured with allogenic T lymphocytes prepared from brachial lymph nodes
      of C57BL/6 mice. Some cultures of non-pregnant female DCs were treated by 2.5%
      serum obtained from pregnant mice at early, middle or late gestational periods,
      and were used in the same mixed lymphocyte reaction (MLR) settings. Cell
      proliferation was measured by 3H-thymidine incorporation, and cytokine production
      measured in supernatants of MLR cultures using ELISA. The effect of pregnant
      mouse serum on expression of DC surface markers was evaluated by flow cytometry.
      No significant difference was found between stimulatory potential of splenic DCs
      from pregnant and non-pregnant mice in induction of allogenic T cell
      proliferative response. Moreover, serum of early or late pregnancy did not have
      any effect on DC function in comparison with non-pregnant mouse serum, while mid
      pregnancy serum significantly inhibited allostimulatory activity of DCs. IFNgamma
      production in co-culture of DCs treated with pregnant mouse serum was
      significantly lower than that of the control group; however, no significant
      difference in IL-10 production was observed. Treatment of DCs with pregnant mouse
      serum did not influence the percentage of cells expressing MHC-II, CD86, CD8alpha
      or CD11b. However, a marked reduction of the mean fluorescence intensity of MHC
      II was observed. Collectively, our results concerning the diminished capacity of
      DCs to induce production of Th1 cytokines and allogenic T cell proliferation
      after treatment with pregnant mouse serum reveal a new way of immunologic
      tolerance against the semi-allogenic fetus.

PMID- 17434210
TI  - In vivo priming heterophil innate immune functions and increasing resistance to
      Salmonella enteritidis infection in neonatal chickens by immune stimulatory CpG
      oligodeoxynucleotides.
AB  - Oligodeoxynucleotides (ODN) containing CpG dinucleotides (CpG-ODN) mimic
      bacterial DNA and stimulate the innate immune system of vertebrates. Here, we
      investigated the effects of intraperitoneal (ip) administered CpG-ODN on the
      innate immune functions of chicken heterophils. Our results demonstrated CpG-ODN
      dependent priming of chicken heterophil degranulation and oxidative burst.
      Heterophils from chickens treated with CpG-ODN exhibited significantly higher
      (p<0.05) degranulation activity compared to PBS and control ODN (ODN containing
      no CpG motif) treated groups when stimulated with opsonized Salmonella enterica
      serovar enteritidis. Similarly, oxidative burst activity, which generates
      bactericidal reactive oxygen species, was significantly higher (p<0.05) in
      heterophils from the CpG-ODN treated group than from PBS and control ODN groups
      when stimulated with formalin-killed S. enteritidis. The priming effects of CpG
      ODN on heterophil immune functions continued at least 4 days post-treatment. In
      the infection study, newly hatched chickens were treated with CpG-ODN, control
      ODN or PBS for 24h then challenged with oral inoculation of S. enteritidis. A
      significant reduction (p<0.05) in colonization by S. enteritidis was observed in
      chickens treated with CpG-ODN. Our study provides evidence that immunostimulatory
      CpG-ODN potentiates the innate immune responses of heterophils and enhances
      resistance to infectious pathogens in neonatal chickens.

PMID- 17434211
TI  - Dichotomous effects of C-C chemokines in HIV-1 pathogenesis.
AB  - Chemokines play a critical role in shaping innate and adaptive immunity. These
      molecules also participate in maintaining the immune balance in the body. Apart
      from their regulatory role, these mediators are involved in several inflammatory
      and autoimmune diseases including viral infection such as HIV-1/AIDS. Chemokine
      co-receptor CCR5 and CXCR4 and their ligands significantly contribute to HIV-1
      disease progression. C-C chemokines such CCL3, CCL4 and CCL5 have been shown to
      possess antiviral effects by binding to HIV-1 co-receptors. CCL2, a member of the
      C-C chemokine family, displays a different feature instead. It is a potential
      enhancer rather than inhibitor of viral replication, a property exhibited by most
      of the C-C chemokine members. In addition, the role of CCL2 is well established
      in forming a Th2 type of response by directing differentiation of Th0 cells
      towards Th2 type, a unique feature of HIV-1 disease. We propose a hypothesis in
      which the chemotactic nature of CCL2 drives recruitment of target cells to the
      site of infection as one of the mechanisms operating in vivo that favours viral
      replication and eventually a high viral load in infected individuals.

PMID- 17434212
TI  - Safety of ofloxacin (OFLX) and fosfomycin sodium (FOM) ear drops.
AB  - OBJECTIVE: The objective of this study is to evaluate the safety of two ear
      drops, Ofloxacin (OFLX: Taribid Otic Solution, Daiichi Seiyaku) and Fosfomycin
      sodium (FOM: Fosmicin S, Meiji Seiyaku). METHODS: Albino guinea pigs were used as
      experimental animals, and the ototoxicity was evaluated by means of threshold
      changes in the compound action potentials (CAP), when topically applied to the
      middle ear cavity of the guinea pig. The sound stimuli applied were; click sound,
      with tone bursts of 8 kHz, 4 kHz, and 2 kHz. In one group of animals, after one
      application of the ear drops in the right middle ear cavity, the change in CAP
      was compared with a contralateral saline control at 24h, one week, and four
      weeks. In other group of animals, the ear drops were applied into the middle ear
      cavity for seven consecutive days and the CAP was measured at 24h. RESULTS: At
      24h the CAP threshold for click, 8 and 4 kHz elevated significantly for both the
      saline and ear drop treatment, but the threshold returned to normal when measured
      at 7 days and 28 days. Seven consecutive days of ear drops administration
      resulted in no reduction in the CAP for either ear drops. CONCLUSIONS: Based on
      the lack of changes in the CAP, these two ear drops studied did not show any
      significant ototoxicities.

PMID- 17434213
TI  - Evaluation of reference genes for quantitative real-time PCR in Ostertagia
      ostertagi by the coefficient of variation and geNorm approach.

PMID- 17434214
TI  - Axenfeld-Rieger syndrome and pseudotruncus arteriosus.
AB  - Axenfeld-Rieger syndrome (ARS) is an autosomal dominant disorder. It is described
      as the association of malformation of the anterior chamber of the eye with
      extraocular anomalies. Cardiovascular defects are considered an occasional
      findings with this syndrome. We present a patient having the features of Axenfeld
      Rieger syndrome with pseudotruncus arteriosus as a different cardiac association.

PMID- 17434215
TI  - D-ribose improves cardiac contractility and hemodynamics, and reduces expression
      of c-fos in the hippocampus during sustained slow ventricular tachycardia in
      rats.
AB  - BACKGROUND: Moderate hypotension during hemodynamically stable ventricular
      tachycardia (VT), leads to cerebral ischemia. Supplementation of d-ribose has
      been shown to improve cardiac metabolism. We hypothesized that cerebral ischemia
      during slow VT may lead to the expression of immediate early genes related to
      neurodegeneration. This expression may be prevented by d-ribose substitution.
      METHODS: Slow VT was induced over 20 min by external left ventricular pacing
      after infusion of physiologic saline or d-ribose (450 mg/kg) in 44 rats.
      Different coloured microspheres were used for tissue blood flow measurements.
      Histochemistry of c-fos in cerebral tissue sections was performed. RESULTS: With
      the onset of VT, the mean arterial pressure (MAP) significantly dropped in both
      groups. However, the MAP in the d-ribose group was significantly higher (p<0.05)
      than in the control group (111+/-21 mm Hg vs. 80+/-40 mm Hg). The rate pressure
      product (RPP) during VT was significantly higher in the d-ribose group than in
      the control group (75,000 vs. 59,000, p<0.05). The occurrence of lethal VT was
      significantly higher in the control group and could be prevented by d-ribose. A
      stable activation of c-fos was observed in the control group. This ischemic
      stress response of the brain could not be seen after d-ribose infusion.
      CONCLUSION: d-ribose improves hemodynamic parameters, cardiac contractility and
      prevents the activation of pro-apoptotic c-fos, demonstrating a neuroprotective
      effect of d-ribose during slow VT.

PMID- 17434216
TI  - Short- and long-term effects of growth hormone on the heart.
AB  - OBJECTIVE: To make a critical analysis of using growth hormone (GH) in patients
      with chronic heart failure and to asses its effects on the heart in long-term
      replacement. METHODS: We have studied 27 GHD patients (20 men; mean age: 36+/-15
      years; 11 with childhood onset GHD) in a longitudinal, prospective study to
      assess the effect of GH therapy on the cardiovascular system with a long-term
      follow-up. RESULTS: After a mean period of 45.3+/-29.6 months, there were no
      significant differences in echocardiographic parameters of cardiac structure or
      function. By contrast, the duration of exercise test improved after treatment
      (8:19+/-3:27 versus 10:23+/-3:25 min; p=0.01) especially in the subgroup of
      patients with childhood onset of GH deficiency (7:02+/-4:23 versus 11:33+/-3:07
      min; p=0.004) but not in the adult onset GHD subgroup. Systolic blood pressure
      was significantly higher after treatment in the global group (118+/-18.2 mmHg
      versus 128+/-17.9 mmHg; p=0.004) and in both subgroups. CONCLUSIONS: The
      beneficial effects of GH replacement on the cardiovascular system is suggested
      but not fully proved and long-term GH substitution in GHD syndrome is not
      associated with significant changes in cardiac structure or function although
      these patients exhibit improved exercise capacity.

PMID- 17434217
TI  - Effect of introducing piglets from farrow-to-finish breeding farms into all-in
      all-out fattening batches in Spain on productive parameters and economic profit.
AB  - A prospective study was conducted to assess the effect of introduction of piglets
      from farrow-to-finish farms on the global performance of all-in all-out fattening
      batches in Galicia (NW Spain). Two hundred and thirty-nine fattening batches from
      48 fattening farms integrated in a cooperative were used in the study. All-in all
      out fattening batches were classified according to the category of farm that
      supplied the piglets. Origin F was a fattening batch where all feeder piglets
      came from one or more farrow to feeder units versus origin FF, in case a group of
      piglets or all piglets of the batch came from farrow-to-finish farms. Productive
      parameters of fattening batches included in the study were recorded. Crude
      comparisons of performance of 37 fattening batches from origin F and 202 from
      origin FF were made. Mixed multiple linear regression models were used to assess
      the association between type of origin of feeder piglets and the following
      parameters: feed consumed per market hog, percentage of deaths (mortality) and
      time to slaughter. In all models, variables with presumable relationships with
      the outcomes were offered to the models as well as the biologically plausible
      interaction terms. Mortality was higher in fattening batches with piglets coming
      from farrow-to-finish farms (0.67% higher than origin F; P<0.05). Time to
      slaughter was longer when feeder piglets were from origin FF (3.1 days longer;
      P<0.05). We found a significant effect of type of origin on feed consumed per
      marketed hog. Additionally, a significant interaction was found: feed consumed
      per marketed hog was higher for fattening batches with all piglets from farrow-to
      finish farms if slaughtered before 109 days and vice versa. A Monte Carlo
      simulation model was used to assess the economic impact of using origin F or FF
      as source of piglets. Results of the model indicated that the difference in
      expected profit per marketed hog between the types of sources of piglets was
      small (11.50 Euros, S.D. 1.79 for origin F versus 10.44 Euros, S.D. 2.72, for
      origin FF).

PMID- 17434218
TI  - Handmade cloning: the future way of nuclear transfer?
AB  - The topic of this review is an alternative technique for somatic cell nuclear
      transfer. Removal of the zona pellucida facilitates manipulations of mammalian
      oocytes and early embryos, and problems related to their subsequent culture are
      commonly overestimated. This approach enables radical modifications to somatic
      cell nuclear transfer, and the handmade cloning (HMC) technique is now
      successfully applied to an increasing numbers of species. HMC radically decreases
      costs and the need for a skilled workforce; furthermore, it increases
      productivity, enables cryopreservation, and results in birth rates comparable, or
      even higher, than those achievable by micromanipulation-based traditional cloning
      (TC). The new technique can accelerate technology transfer and standardization
      and, eventually, might contribute to the widespread application of cloning.
      Additionally, HMC offers unique possibilities for the automation of somatic cell
      nuclear transfer.

PMID- 17434219
TI  - Yoghurt fermented by Lactobacillus delbrueckii subsp. bulgaricus H+ -ATPase
      defective mutants exhibits enhanced viability of Bifidobacterium breve during
      storage.
AB  - Persistent acid production by Lactobacillus delbrueckii subsp. bulgaricus during
      refrigerated storage is a major cause of reduced viability of probiotic strains
      such as Bifidobacterium breve in yoghurt. It was established that H+ -ATPase
      defective mutants of lactic acid bacteria have reduced growth and metabolism in
      low pH environments. Therefore, the aim of this study was to evaluate inhibition
      of post-acidification and maintenance of B. breve viability in yoghurt fermented
      by L. delbrueckii subsp. bulgaricus mutants with reduced membrane-bound H+ 
      ATPase activity during refrigerated storage. Spontaneous neomycin mutants of L.
      delbrueckii subsp. bulgaricus that had a significantly (P < or = 0.05) reduced H+
      -ATPase activity were successfully isolated. Yoghurt fermented using L.
      delbrueckii subsp. bulgaricus SBT0164 No. 55-1 (mutant) starter culture had
      markedly reduced post-acidification and maintained viability (> or = 10(8)
      CFU/ml) of both Bifidobacteruim breve JCM 1192(T) and Bifidobacteruim breve JCM
      7017 during storage at 10 degrees C for 21 days. These results clearly showed
      that yoghurt fermented by mutants of L. delbrueckii subsp. bulgaricus with
      reduced membrane-bound H+ -ATPase activity has reduced post-acidification that
      prolongs viability of B. breve in yoghurt during refrigerated storage.

PMID- 17434220
TI  - Screening of various foodstuffs for occurrence of Coxiella burnetii in
      Switzerland.
AB  - The epidemiology of Q-fever in Switzerland is largely unknown. For this reason, a
      screening programme for the presence of Coxiella burnetii in bulk milk samples
      from cows, sheep and goats and in shell eggs produced in and imported into
      Switzerland was conducted. In total, 17 of 359 (4.7%) of analysed bovine milk
      samples from two randomly selected cheese dairies were tested positive for C.
      burnetii by nested PCR. Furthermore, the findings with samples from one dairy
      showed that the agent seemed to persist over time in the herds of cattle of
      certain farms. Although no extensive prevalence study was undertaken, our results
      indicate that C. burnetii appears to be quite frequent in cattle. As for 81 ovine
      and 39 caprine bulk milk samples, they were all tested negative for C. burnetii.
      Finally, 504 shell eggs were also found to be negative for C. burnetii with PCR
      testing. The results of the study are discussed under inclusion of
      epidemiological data for human and animal coxiellosis and the current Swiss legal
      regulations for the control of C. burnetii in cattle.

PMID- 17434221
TI  - Surprising production of a new urdamycin derivative by S. fradiae Delta urdQ/R.
AB  - A strain (S. fradiae Delta urdQ/R) with mutations in urdQ and urdR encoding a
      dTDP-hexose-3,4-dehydratase and a dTDP-hexose-4-ketoreductase, respectively,
      produces a new urdamycin analogue (urdamycin X) with changes in the polyketide
      structure. The structure of urdamycin X has been elucidated by NMR spectroscopy.
      Urdamycin X was not detectable, even in small amounts, in either S. fradiae Delta
      urdQ, in S. fradiae DeltaurdR or in S. fradiae A0, a mutant lacking all
      glycosyltransferase genes. Complementation of S. fradiae Delta urdQ/R restored
      urdamycin A production indicating that the mutations did not cause any polar
      effect.

PMID- 17434222
TI  - An integrated process: ester synthesis in an enzymatic membrane reactor and water
      sorption.
AB  - In the case of such reactions as ester synthesis, water is produced during the
      reaction. Because these reactions are carried out in hydrophobic solvents an
      additional (water) phase in the system must not be allowed, i.e. the
      concentration of water saturation in the organic solvent should not be exceeded.
      In such a case, the reaction kinetics and product equilibrium concentration
      undergo undesirable changes because of the partition coefficient of the
      components and hampered process of product separation. Hence, removal of the
      water produced in the reaction determines whether the process is successful or
      not. For this purpose, the integrated process with water sorption in the column
      with molecular sieves was applied. Integration of the process of synthesis and
      dehydration of a reaction phase, in which a biocatalyst is suspended and not
      dissolved as in water solutions, requires holding up of the catalyst in the
      reactor before directing the stream of reaction mixture to dehydration process.
      This hold-up and a possibility of multiple use of the catalyst may be
      accomplished by using a separating barrier, e.g. an ultrafiltration membrane or
      by permanent fixing of the catalyst to the matrix, e.g. a polymeric membrane. The
      efficiency and activity of a biocatalyst (lipase CAL-B) immobilized on a polymer
      membrane by sorption and chemical binding, were determined. A subject of study
      was the synthesis of geranyl acetate, one of the most known aromatic compound. A
      hydrophobic (polypropylene) matrix was shown to be a much better carrier in the
      reactions performed in an organic solvent than a hydrophilic (polyamide) membrane
      being tested. The reaction kinetics of geranyl acetate synthesis with the use of
      geraniol and acetic acid as substrates, was described by the equation defining
      the "Ping-Pong Bi Bi" mechanism that was related additionally to the inhibition
      of a substrate (acetic acid). The following constants of kinetic equation were
      obtained k(3)(')=0.344 mol g(-1)h(-1), K(mA)=0.257 mol l(-1), K(mG)=1.629 and
      K(iA)=0.288 for the native enzyme and v(max,Gel)=111.579 mol l(-1)h(-1),
      K(mA)=0.255 mol l(-1), K(mG)=1.91 mol l(-1), K(iA)=0.238 mol l(-1) for the one
      immobilized by sorption on a polypropylene membrane. Half-life time of the native
      enzyme activity was 204 h and stability of the immobilized preparation was 70 h.
      With respect to the reaction kinetics and stability of the native enzyme and
      immobilized preparation, from both types of membrane bioreactor more attractive
      appears to be the one in which the membrane is used not as a catalyst layer but
      only as a barrier that immobilizes the native enzyme within the bioreactor
      volume. When an integrated process proceeds, the method to collect water in the
      sorption column during the process, appeared to work very well. The reaction
      proceeded with a very high efficiency (after 120 h alpha=98.2% for native enzyme
      and 83.2% for immobilized enzyme) and due to low water concentration in the
      system ( approximately 0.000% v/v) the second phase was not created.

PMID- 17434223
TI  - Functional characterization of putative promoter elements from infectious
      hypodermal and hematopoietic necrosis virus (IHHNV) in shrimp and in insect and
      fish cell lines.
AB  - Infectious hypodermal and hematopoietic necrosis virus (IHHNV) of shrimp contains
      a linear single-stranded DNA genome of approximately 4.1kb with three putative
      open reading frames (ORFs) on the same DNA strand designated, the Left, Middle,
      and Right ORFs. The Left ORF codes for non-structural protein and the Right ORF
      codes for capsid protein, whereas the role of the Middle ORF is still unknown.
      Two putative promoters, designated P2 and P61, were detected upstream of the Left
      ORF and Right ORF, respectively. We evaluated the activities of these two
      promoters with or without a transcriptional enhancer element via the use of
      firefly luciferase reporter constructs in insect and fish cells, and in shrimp
      tail muscle. In insect and fish cells, the P2 promoter was stronger than the P61
      promoter. The presence of the SV40 enhancer element negatively affected P2 but
      not P61 promoter activity in insect cells. However, in fish cells, the SV40
      enhancer element dramatically increased the activities of both promoters. In
      shrimp, there was no significant difference in luciferase expression driven by
      these two promoters. In shrimp tail muscle, the presence of SV40 enhancer element
      in the construct had no significant effect on the P2 promoter and a negative
      effect on the P61 promoter. The IHHNV P2 and P61 promoters were found to be
      constitutive promoters that can drive gene expression in both invertebrate and
      vertebrate hosts.

PMID- 17434224
TI  - Cellular segregation of feline leukemia provirus and viral RNA in leukocyte
      subsets of long-term experimentally infected cats.
AB  - Cats exposed to feline leukemia virus (FeLV) may develop different outcomes of
      the infection. However, during acute infection blood proviral and viral RNA loads
      of cats with progressive and regressive infection are not significantly
      different. Thus, not the overall loads but rather those of specific leukocyte
      subsets may influence the infection outcome. By combining fluorescence activated
      cell sorting (FACS) with sensitive real-time TaqMan PCR and reverse transcriptase
      (RT) PCR, we established in the present study the methods to determine FeLV
      proviral and viral RNA loads in specific leukocyte subsets. In addition, they
      were applied to analyze long-term persistently FeLV-infected (p27-positive) and
      FeLV exposed but nonantigenemic (p27-negative), nonviremic cats. In the latter
      animals, CD4(+) and B lymphocytes exhibited the highest proviral loads, whereas
      in p27-positive cats, all leukocyte subsets showed similar high loads. In p27
      positive cats, monocytes and granulocytes bore the highest viral RNA loads,
      whereas only one p27-negative cat was positive for viral RNA in T lymphocytes. To
      our knowledge, this is the first study to investigate FeLV proviral and viral RNA
      loads in leukocyte subsets of FeLV exposed cats. The herein described methods are
      important prerequisites to gain a deeper insight into the pathogenesis of FeLV
      infection.

PMID- 17434225
TI  - Effects of surface coating on the controlled release of vitamin B1 from
      mesoporous silica tablets.
AB  - The controlled release of vitamin B1 (VB1, thiamine hydrochloride) from
      mesoporous silica tablets coated with a series of sol-gel coatings was
      investigated. Tetraethoxysilane (TEOS), n-propyltriethoxysilane (PTES), n
      octyltriethoxysilane (OTES), bis(trimethoxysilyl)hexane (TSH),
      bis(triethoxysilyl)octane (TSO), bis (trimethoxysilylpropyl)amine (TSPA), and
      bis[(3-trimethoxysilyl)propyl]ethylenediamine (TSPED) were used as precursors for
      the coatings. The effects of organosilane type and concentration, the number of
      coatings, drying temperature, and release media on VB1 release from the coated
      mesoporous silica tablets were comprehensively examined. The TSH, TSO, TSPA, and
      TSPED coatings were found to be more effective in suppression of release than the
      other coatings. VB1 release decreases with the increase in the number of coatings
      and drying temperature. It was found that there is an optimal coating solution
      concentration for the controlled release. In general, more VB1 is released in
      0.01 M HCl solution than in 0.05 M phosphate buffer solution at pH 7.4 because of
      the electrostatic repulsions between the protonated VB1 cations and the
      positively charged mesoporous silica carrier/coatings. The experimental results
      show that drug release can be easily controlled by changing the organosilane type
      and the number of coating. The method used in this study is an effective and
      flexible way for controlled release due to the high drug loading and the easy
      control of release rate.

PMID- 17434226
TI  - [Electrophysical surveillance in limb lengthening in 25 children and
      adolescents].
AB  - OBJECTIVE: To evaluate neurological tolerance during limb lengthening in children
      and adolescents. MATERIAL AND METHODS: Retrospective study of 25 children and
      adolescents [15 girls, 10 boys; mean age 11.3 years, range 5-18 years] undergoing
      limb lengthening. Limbs involved were the femur [11 cases], tibia [10 cases],
      radius [3 cases] and humerus [1 case], and lengthening was 1 mm/day, adjusted
      depending on clinically and electrophysically observed alterations during weekly
      surveillance. RESULTS: Lengthening in 8 cases was accompanied by
      electrophysiological deterioration and in 1 by clinical alteration without
      electrophysiological anomaly. Eight of 25 lengthenings had to be slowed and 1
      discontinued. DISCUSSION: This work confirms poor neurological tolerance with
      limb lengthening. It shows the interest of clinical and electrophysiological
      monitoring in preventing severe neurological accidents with such lengthening.

PMID- 17434227
TI  - Glycated albumin is low in obese, type 2 diabetic patients.
AB  - This study is to clarify whether obesity status affects glycated albumin (GA) and
      HbA1c levels in adults with type 2 diabetes. One hundred and seven individuals
      with type 2 diabetes without advanced complications participated in this study.
      The relationship between HbA1c, GA, hemoglobin (Hb), albumin (ALB), absolute
      value of GA (aGA) and Body Mass Index (BMI) were examined using Pearson's
      correlation coefficient. The comparison of each parameter was conducted using
      unpaired t-test between the obese (BMI> or =25) and the non-obese (BMI<25) group.
      Additionally the multiple regression analyses to find factors related with GA
      (i.e. BMI, HbA1c, age, ALB and the insulin therapy) were performed. HbA1c level
      and BMI showed very weak correlation (r=-0.04; p=0.65). However, GA, aGA and BMI
      showed a significant negative correlation (r=-0.28; p=0.004, r=-0.22; p=0.024).
      The GA and aGA values of the obese group were significant lower than those in the
      non-obese group. In multiple regression analysis, BMI (beta=-0.24; p=0.001) was
      negatively, and HbA1c (beta=3.65; p<0.001) was positively correlated with GA. In
      conclusion, the current analysis demonstrated a need of careful evaluation of GA
      values in obese diabetic patients in daily practice. Further researches are
      required to elucidate the underlying mechanisms.

PMID- 17434229
TI  - Survival of liver failure pigs by transplantation of reversibly immortalized
      human hepatocytes with Tamoxifen-mediated self-recombination.
AB  - BACKGROUND/AIMS: Hepatocyte transplantation and bioartificial liver treatment are
      attractive alternatives to liver transplantation. The availability of well
      characterized human hepatocyte lines facilitates such cell therapies. METHODS:
      Human hepatocytes were immortalized with a retroviral vector SSR#197 expressing
      catalytic subunit of human telomerase reverse transcriptase (hTERT) and enhanced
      green fluorescent protein (EGFP) cDNAs flanked by a pair of loxP recombination
      targets. Then, Tamoxifen-dependent Cre recombinase was expressed in SSR#197
      immortalized hepatocytes. Cre/LoxP recombination was performed in the established
      cells by simple exposure to 500 nM Tamoxifen for a week. Then, the reverted
      population of the cells was recovered by EGFP-negative cell sorting and
      characterized in vitro and in vivo using a pig model of acute liver failure (ALF)
      induced by d-galactosamine (0.5 g/kg) injection. RESULTS: A human hepatocyte cell
      line 16T-3 was established. Reverted 16-T3 cells showed the increased expression
      of hepatic markers in association with enhanced levels of transcriptional
      factors. Compared to normal human hepatocytes, albumin production and lidocaine
      metabolizing activities of reverted 16-T3 cells were 0.32 and 0.50-fold,
      respectively. Transplantation of reverted 16T-3 cells significantly prolonged the
      survival of ALF pigs. CONCLUSIONS: Here we demonstrate the usefulness of Cre/LoxP
      -mediated reversible immortalization of human hepatocytes with Tamoxifen-mediated
      self-recombination.

PMID- 17434228
TI  - Treatment with 2-AAF blocks the small hepatocyte-like progenitor cell response in
      retrorsine-exposed rats.
AB  - BACKGROUND/AIMS: Liver regeneration after partial hepatectomy (PH) in retrorsine
      exposed rats is accomplished through proliferation and differentiation of small
      hepatocyte-like progenitor cells (SHPCs). The cells of origin of SHPCs are not
      known. We investigated the possibility that SHPCs are directly derived from oval
      cells, a known liver progenitor cell, by combining the retrorsine/PH (RP) model
      with 2-acetamidofluorene (2-AAF), an anti-mitotic agent that elicits an oval cell
      reaction in response to liver deficit. METHODS: Male Fischer 344 rats were
      treated with retrorsine (30 mg/kg ip) at 6 and 8 weeks of age, with PH 5 weeks
      after the final treatment. Seven days prior to PH, a 21-day 2-AAF (50mg) time
      release pellet was inserted subcutaneously. Livers were harvested at 3, 7, 10,
      14, and 21-days post-PH. RESULTS: Liver sections from animals treated with 2
      AAF/retrorsine/PH (2-AAF/RP) contain significant numbers of proliferating oval
      cells, but no SHPCs at 7-days post-PH, while RP animals exhibit significant
      numbers of SHPCs and minimal oval cell reaction. Between 10 and 14-days post-PH,
      new hepatocyte clusters appear in 2-AAF/RP treated rats. Labeling of
      proliferating oval cells with BrdU at 6-days post-PH demonstrated that these new
      hepatocytes represent the progeny of differentiating oval cells. CONCLUSIONS: The
      observed differences in progenitor cell responses between 2-AAF/RP and RP animals
      strongly suggest that SHPCs are not the progeny of oval cell precursors, but
      represent an independent liver progenitor cell population.

PMID- 17434230
TI  - Oxidative stress induces the endoplasmic reticulum stress and facilitates
      inclusion formation in cultured cells.
AB  - BACKGROUND/AIMS: The precise mechanism of formation and significance of Mallory
      bodies (MBs) are poorly understood. The endoplasmic reticulum (ER) is the
      organelle responsible for proper folding and elimination of unfolded proteins.
      Therefore, failure of this function increases defective proteins in the cell.
      METHODS: We examined the effects of oxidative stress on induction of ER stress
      and keratin 8 and 18 (K8/18)-containing inclusion formation in cultured human
      hepatoma cells and hepatocytes by immunofluorescence and immunoblot analyses.
      RESULTS: Generation of H(2)O(2) was detected in glucose oxidase (GO)-treated
      cells by 2',7'-dichlorodihydrofluorescein diacetate and co-treatment with GO and
      acetyl-leucyl-leucyl-norleucinal (ALLN), a proteasome inhibitor, induced
      formation of extensive keratin inclusions that were inhibited by pre-treatment
      with N-acetyl-cysteine. These inclusions shared similar features with MBs by
      immunofluorescence analysis. Electron microscopy showed that these structures
      appeared near the nuclei, surrounded by filamentous structures. GO and ALLN
      upregulated the expression of ER stress markers, however, 4-phenylbutyrate, a
      chemical chaperone, reduced formation of inclusions and expression of the ER
      stress markers. CONCLUSIONS: The oxidative stress coupled with limited inhibition
      of the proteasome induces dysfunction of the ER and results in inclusion
      formation in cultured cells. This suggests that ER stress plays a role in MB
      formation in liver disease.

PMID- 17434231
TI  - Maternal hepatitis B infection and gestational diabetes mellitus.
AB  - BACKGROUND/AIMS: This retrospective cohort study was performed to examine the
      relationship between maternal hepatitis B virus infection, as indicated by the
      surface antigen status, with the development of gestational diabetes mellitus in
      a normal-risk Chinese obstetric population. METHODS: Maternal demographics, risk
      factors, and pregnancy outcome of 13,683 singleton pregnancies delivering in 1998
      2001 were analysed according to maternal hepatitis B surface antigen status,
      which was routinely screened. Multiple logistic regression analysis was performed
      to examine the role of hepatitis B infection in the development of gestational
      diabetes mellitus. RESULTS: The 1138 women (8.3%) with hepatitis B infection had
      lower mean weight and body mass index, similar prevalence of chronic medical
      diseases and smokers, but increased prevalence of gestational diabetes mellitus,
      which remained significant (odds ratio 1.24, 95% confidence interval 1.01-1.51)
      after adjustment for confounding variables. However, there was no difference in
      pregnancy outcome. CONCLUSIONS: Our results confirmed the independent association
      between hepatitis B infection with gestational diabetes mellitus. The magnitude
      of chronic hepatitis B infection in the developing world and certain ethnic
      groups could have contributed to the high prevalence of gestational and possibly
      type 2 diabetes in these populations. Further studies on the long-term
      implications of our finding are warranted.

PMID- 17434232
TI  - Evolution of microbial virulence: the benefits of stress.
AB  - Although genome sequencing of microbial pathogens has shed light on the evolution
      of virulence, the drivers of the gain and loss of genes and of pathogenicity
      islands (gene clusters), which contribute to the emergence of new disease
      outbreaks, are unclear. Recent experiments with the bean pathogen Pseudomonas
      syringae pv. phaseolicola illustrate how exposure to resistance mechanisms acts
      as the driving force for genome reorganization. Here we argue that the
      antimicrobial conditions generated by host defences can accelerate the generation
      of genome rearrangements that provide selective advantages to the invading
      microbe. Similar exposure to environmental stress outside the host could also
      drive the horizontal gene transfer that has led to the evolution of pathogenicity
      towards both animals and plants.

PMID- 17434233
TI  - Playing hide and seek with mammalian meiotic crossover hotspots.
AB  - Crossovers (COs) are essential for meiosis and contribute to genome diversity by
      promoting the reassociation of alleles, and thus improve the efficiency of
      selection. COs are not randomly distributed but are found at specific regions, or
      CO hotspots. Recent results have revealed the historical recombination rates and
      the distribution of hotspots across the human genome. Surprisingly, CO hotspots
      are highly dynamic, as shown by differences in activity between individuals,
      populations and closely related species. We propose a role for DNA methylation in
      preventing the formation of COs, a regulation that might explain, in part, the
      correlation between recombination rates and GC content in mammals.

PMID- 17434234
TI  - Boundary element method for prediction of hardness of dentin from punch-nano
      indentation test.
AB  - In this paper, a quadratic boundary element formulation for prediction of
      hardness of dentin from punch-nano-indentation test is presented. BE contact
      formulation is given. The initial strain formulation and von Mises yield criteria
      are employed to cover plastic deformation. The dentin is assumed to be isotropic,
      homogenous and elastic-perfectly plastic material. The load versus displacement
      is obtained during loading-unloading sequence for different yield strength and
      elastic modulus. Hardness and equivalent residual stresses are plotted for
      different elastic modulus depending on yield strength. BE method is shown to be
      an alternative accurate computational tool for simulated nano-indentation tests.

PMID- 17434235
TI  - shRNA and siRNA delivery to the brain.
AB  - The limiting factor in in vivo RNA interference (RNAi) is delivery. Drug delivery
      methods that are effective in cell culture may not be practical in vivo for
      intravenous RNAi applications. Nucleic acid drugs are highly charged and do not
      cross cell membranes by free diffusion. Therefore, the in vivo delivery of RNAi
      therapeutics must use targeting technology that enables the RNAi therapeutic to
      traverse biological membrane barriers in vivo. For RNAi of the brain, the nucleic
      acid-based drug must first cross the brain capillary endothelial wall, which
      forms the blood-brain barrier (BBB) in vivo, and then traverses the brain cell
      plasma membrane. Similar to the delivery of non-viral gene therapies, plasmid DNA
      encoding for short hairpin RNA (shRNA) may be delivered to the brain following
      intravenous administration with pegylated immunoliposomes (PILs). The plasmid DNA
      is encapsulated in a 100 nm liposome, which is pegylated, and conjugated with
      receptor specific targeting monoclonal antibodies (MAb). Weekly, intravenous RNAi
      with PILs enables a 90% knockdown of the human epidermal growth factor receptor,
      which results in a 90% increase in survival time in mice with intra-cranial brain
      cancer. Similar to the delivery of antisense agents, short interfering RNAi
      (siRNA) duplexes can be delivered with the combined use of targeting MAb's and
      avidin-biotin technology. The siRNA is mono-biotinylated in parallel with the
      production of a conjugate of the targeting MAb and streptavidin. Intravenous RNAi
      requires the combined use of RNAi technology and a drug targeting technology that
      is effective in vivo.

PMID- 17434236
TI  - Gefitinib as palliative therapy for lung adenocarcinoma metastatic to the brain.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer deaths in most countries.
      In patients with metastases, such as the brain, the 1-year survival is 10% and
      most of these patients die in 1-3 months. Data from large phase II trials of non
      small cell lung cancer (NSCLC) suggested that the histologic subtype of
      adenocarcinoma may be a prognostic factor for patients treated with gefitinib. To
      evaluate the efficacy of gefitinib in palliative therapy for advanced patients
      with adenocarcinoma and brain metastases, we conducted a phase II study. PATIENTS
      AND METHODS: Eligible patients had histologically confirmed adenocarcinoma and
      brain metastases confirmed with radiological studies. All eligible patients had
      undergone chemotherapy previously. From December 2003 to December 2004, 40
      patients received 250mg doses of gefitinib daily. The symptomatic response,
      survival, and toxicity were recorded. RESULTS: The overall objective response
      rate was 32% with a disease control rate of 77%. Altogether, 45% of the patients
      experienced symptom improvement. The median progression-free survival and overall
      survival were 9.0 months and 15.0 months, respectively. Gefitinib was well
      tolerated, with cutaneous reactions as the most frequent toxicity. CONCLUSIONS:
      Our data suggest that gefitinib has promising activity in palliative therapy for
      patients with advanced lung adenocarcinoma and brain metastasis.

PMID- 17434237
TI  - Marine ecology warms up to theory.
AB  - A recent report by O'Connor et al. demonstrates that planktonic larval duration
      time declines with temperature, as predicted from metabolic theory. This
      observation enabled the authors to develop a unified model predicting the effects
      of temperature on planktonic larval duration and, therefore, dispersal potential
      in the marine environment. These results show metabolic theory to be a unifying
      ecological principle that bridges the marine and terrestrial divide, helping to
      address fundamental problems in marine biodiversity and conservation, as well as
      to understand the response of marine organisms to climate change.

PMID- 17434238
TI  - Electronic surveillance of wall-mounted soap and alcohol gel dispensers in an
      intensive care unit.
AB  - We describe a battery-powered recording device incorporating a force-sensitive
      resistor and a microcontroller that records depressions of wall-mounted soap and
      alcohol gel dispensers. The device has a two-second (2 s) lockout built into it,
      so that a single record is associated with a single hand-hygiene episode.
      Recorders were implanted within the wall-mounted dispensers found in two bed
      areas and the entrance of a 16-bedded intensive care unit. The use of the bed
      area dispensers was correlated (r) with the dependency of the patient in the open
      bed area (r=0.5, P<0.01), as assessed using the UK Department of Health critical
      care minimum data set. Both bed areas and the entrance dispensers showed wide but
      different fluctuations in use throughout the 24h day. The recording device may
      help in feedback about soap and gel use for hand-hygiene quality improvement and
      educational initiatives.

PMID- 17434239
TI  - Age related changes in brain metabolites observed by 1H MRS in APP/PS1 mice.
AB  - Translational biomarkers in Alzheimer's disease based on non-invasive in vivo
      methods are highly warranted. (1)H magnetic resonance spectroscopy (MRS) is non
      invasive and applicable in vivo in both humans and experimental animals. In
      vivo(1)H MRS and 3D MRI were performed on brains of double transgenic (tg) mice
      expressing a double mutant human beta-amyloid precursor protein APP(K670N,M671L)
      and human mutated presenilin gene PS1M146L, and wild-type (wt) littermates at
      2.5, 6.5 and 9 months of age using a 9.4T magnet. For quantification, LCModel was
      used, and the data were analyzed using multivariate data analysis (MVDA). MVDA
      evidenced a significant separation, which became more pronounced with age,
      between tg and wt mice at all time points. While myo-inositol and guanidoacetate
      were important for group separation in young mice, N-acetylaspartate, glutamate
      and macrolipids were important for separation of aged tg and wt mice. Volume
      segmentation revealed that brain and hippocampus were readily smaller in tg as
      compared to wt mice at the age of 2.5 months. Amyloid plaques were seen in 6.5
      and 9 months, but not in 2.5 months old animals. In conclusion, differences in
      brain metabolites could be accurately depicted in tg and wt mice in vivo by
      combining MRS with MVDA. First differences in metabolite content were readily
      seen at 2.5 months, when volume defects in tg mice were present, but no amyloid
      plaques.

PMID- 17434240
TI  - [Transfusion-related acute lung injury].
AB  - OBJECTIVES: The transfusion-related acute lung injury frequency was for a long
      time underestimated since it lacked both a widely accepted clinical definition
      and a comprehensive etiologic description. Recent clinical and biological data
      have underlined its frequency and have allowed a better understanding of its
      mechanisms. CURRENT KNOWLEDGE AND KEY POINTS: Trali is an interstitial lung
      injury occurring within 6 hours after the beginning of a blood transfusion. This
      time relationship between blood injection and the occurrence of lung edema is
      sufficient for a positive diagnosis, if any other cause of interstitial lung
      edema have been excluded. The clinical definition relies on a desaturation of
      arterial blood associated to a lack of any cardiac failure or circulation
      overload. The link between transfusion and lung edema is not univocal and several
      categories of mechanisms have been discussed. At least 2 of them are well
      identified; the first one is an immune conflict, and the second one is an
      activation of neutrophils by injection of biological modifiers such as lipids or
      CD40 soluble ligand. Evidences exist for the occurrence of Trali only in
      predisposing condition that mostly consists of a preceding leucostase in lung
      capillaries. Trali is treated like other lung interstitial edema by oxygen
      therapy and mechanical ventilation. FUTURE PROJECTS: A better knowledge of Trali
      offers the opportunity of improving the understanding of the role of blood
      transfusion in lung edema occurring in complex situations and open the way for a
      better definition of at risk patient and at risk blood components.

PMID- 17434241
TI  - Comment on Hesseling, et al. "The risk of disseminated Bacille Calmette-Guerin
      (BCG) disease in HIV-infected children" [Vaccine 25 (2006) 14-18].

PMID- 17434242
TI  - Formulation of the adenylate cyclase toxin of Bordetella pertussis as protein
      coated microcrystals.
AB  - Adenylate cyclase toxin (CyaA) is an important virulence factor of Bordetella
      pertussis, the causative agent of whooping cough, and, in its detoxified form, a
      potential component of acellular pertussis vaccines. This study reports the
      application of a novel technology, formulation of CyaA as protein-coated
      microcrystals (PCMC), to improve the performance of CyaA as a vaccine component.
      CyaA is normally stored in a high urea concentration to prevent aggregation and
      to maintain stability of the protein. The aim of the work was to stabilise CyaA
      on a crystalline support to create a dry powder that could be reconstituted in
      aqueous buffer, free of urea. CyaA, formulated as PCMC with microcrystals of dl
      valine, retained full adenylate cyclase (AC) and cell invasive (cytotoxic)
      activities after solubilistion in urea buffer. After storage as a dry powder at
      37 degrees C for 2 weeks, the AC activity recovered from the CyaA-PCMC was only
      marginally reduced when solubilised in urea buffer. No AC activity was detected
      after attempts to solubilise CyaA-PCMC in aqueous buffer alone, in the absence of
      urea. Inclusion of various ionic, non-ionic or zwitterionic detergents in the
      aqueous buffer had little effect on recovery of CyaA activities. However,
      preparation of PCMC with CyaA plus calmodulin (CaM) or bovine serum albumin (BSA)
      or with both proteins allowed restoration of AC and cytotoxic activities of CyaA
      upon solubilisation in aqueous buffer. Incorporation of BSA and CaM with CyaA
      allowed essentially full recovery of AC activity but lower recovery of
      cytotoxicity. CyaA-CaM-BSA-PCMC, after reconstitution in aqueous buffer, induced
      a strong serum IgG response to CyaA when injected subcutaneously into mice.

PMID- 17434243
TI  - Need to worry: wrong vitamin A doses reported!

PMID- 17434244
TI  - Generation and evaluation of a recombinant modified vaccinia virus Ankara vaccine
      for rabies.
AB  - Modified vaccinia virus Ankara (MVA) has become a vaccine vector of choice for
      recombinant vaccine development. A MVA-based rabies vaccine would be advantageous
      for use as a vaccine for dogs (and wildlife), particularly if it proves innocuous
      and efficacious by the oral route. Here, the generation and immunological testing
      of a recombinant MVA expressing a rabies virus glycoprotein gene is described. In
      a murine model, higher dosages of recombinant MVA were needed to induce equivocal
      immune responses as with Vaccinia Copenhagen or Vaccinia Western Reserve
      recombinants, when administered by a parenteral route. The MVA recombinant was
      not immunogenic or efficacious when administered per os in naive mice. The
      ability of the recombinant MVA to induce anamnestic responses in dogs and
      raccoons was also investigated. Recombinant MVA boosted humoral immune responses
      in these animals when administered peripherally, but not when administered
      orally.

PMID- 17434245
TI  - Maximum step length: relationships to age and knee and hip extensor capacities.
AB  - BACKGROUND: Maximum Step Length may be used to identify older adults at increased
      risk for falls. Since leg muscle weakness is a risk factor for falls, we tested
      the hypotheses that maximum knee and hip extension speed, strength, and power
      capacities would significantly correlate with Maximum Step Length and also that
      the "step out and back" Maximum Step Length [Medell, J.L., Alexander, N.B., 2000.
      A clinical measure of maximal and rapid stepping in older women. J. Gerontol. A
      Biol. Sci. Med. Sci. 55, M429-M433.] would also correlate with the Maximum Step
      Length of its two sub-tasks: stepping "out only" and stepping "back only". These
      sub-tasks will be referred to as versions of Maximum Step Length. METHODS:
      Unimpaired younger (N=11, age=24[3]years) and older (N=10, age=73[5]years) women
      performed the above three versions of Maximum Step Length. Knee and hip extension
      speed, strength, and power capacities were determined on a separate day and
      regressed on Maximum Step Length and age group. Version and practice effects were
      quantified and subjective impressions of test difficulty recorded. Hypotheses
      were tested using linear regressions, analysis of variance, and Fisher's exact
      test. FINDINGS: Maximum Step Length explained 6-22% additional variance in knee
      and hip extension speed, strength, and power capacities after controlling for age
      group. Within- and between-block and test-retest correlation values were high
      (>0.9) for all test versions. INTERPRETATION: Shorter Maximum Step Lengths are
      associated with reduced knee and hip extension speed, strength, and power
      capacities after controlling for age. A single out-and-back step of maximal
      length is a feasible, rapid screening measure that may provide insight into
      underlying functional impairment, regardless of age.

PMID- 17434246
TI  - Effects of chemical additives on hydrocarbon disappearance and biodegradation in
      freshwater marsh microcosms.
AB  - We determined how a cleaner and a dispersant affected hydrocarbon biodegradation
      in wetland soils dominated by the plant Panicum hemitomon, which occurs
      throughout North and South America. Microcosms received no hydrocarbons, South
      Louisiana crude, or diesel; and no additive, a dispersant, or a cleaner. We
      determined the concentration of four total petroleum hydrocarbon (TPH) measures
      and 43 target hydrocarbons in water and sediment fractions 1, 7, 31, and 186 days
      later. Disappearance was distinguished from biodegradation via hopane
      normalization. After 186 days, TPH disappearance ranged from 24% to 97%. There
      was poor correlation among the four TPH measures, which indicated that each
      quantified a different suite of hydrocarbons. Hydrocarbon disappearance and
      biodegradation were unaltered by these additives under worse-case scenarios. Any
      use of these additives must generate benefits that outweigh the lack of effect on
      biodegradation demonstrated in this report, and the increase in toxicity that we
      reported earlier.

PMID- 17434247
TI  - Toxicity of abamectin and doramectin to soil invertebrates.
AB  - This study aimed at determining the toxicity of avermectins to soil invertebrates
      in soil and in faeces from recently treated sheep. Abamectin was more toxic than
      doramectin. In soil, earthworms (Eisenia andrei) were most affected with LC50s of
      18 and 228 mg/kg dry soil, respectively, while LC50s were 67-111 and >300 mg/kg
      for springtails (Folsomia candida), isopods (Porcellio scaber) and enchytraeids
      (Enchytraeus crypticus). EC50s for the effect on reproduction of springtails and
      enchytraeids were 13 and 38 mg/kg, respectively for abamectin, and 42 and 170
      mg/kg for doramectin. For earthworms, NOEC was 10 and 8.4 mg/kg for abamectin and
      doramectin effects on body weight. When exposed in faeces, springtails and
      enchytraeids gave LC50s and EC50s of 1.0-1.4 and 0.94-1.1 mg/kg dry faeces for
      abamectin and 2.2->2.4 mg/kg for doramectin. Earthworm reproduction was not
      affected. This study indicates a potential risk of avermectins for soil
      invertebrates colonizing faeces from recently treated sheep.

PMID- 17434248
TI  - Chagas disease in Texas: recognizing the significance and implications of
      evidence in the literature.
AB  - Chagas disease is endemic and is recognized as a major health problem in many
      Latin American countries. Despite the parallels between socio-economic and
      environmental conditions in Texas and much of Latin America, Chagas disease is
      not a notifiable human disease in Texas. Based on extensive review of related
      literature, this paper seeks to recognize the evidence that Chagas Disease is
      endemic to Texas but the epidemiological, parasitological and entomological
      patterns of Chagas disease in Texas are both different from and parallel to other
      endemic regions. We find that with a growing immigrant human reservoir, the
      epidemiological differences may be reduced and result in increasing incidence of
      the disease. Chagas disease should be recognized as an emerging disease among
      both immigrant and indigenous populations. Without proper actions, Chagas disease
      will place increasing burden on the health care system. Current medical
      treatments consist of chemotherapies that carry the risk of serious side effects;
      curing the potentially fatal disease remains equivocal. Therefore, as shown in
      South America, prevention is paramount and can be successfully achieved through
      intervention and education. We conclude that biogeographical research is needed
      to (1) distinguish the dynamic evolution of the agent-vector-host system, (2)
      document locations with greater risk and identify mechanisms responsible for
      observed changes in risk, and (3) assist in developing a model for Triatomid
      vector-borne disease in states like Texas where the disease is both endemic and
      may be carried by a sizeable immigrant population. Tracking of Chagas disease and
      planning for appropriate health care services would also be aided by including
      Chagas disease on the list of reportable diseases for humans.

PMID- 17434249
TI  - Metabolism of 2-substituted quinolines with antileishmanial activity studied in
      vitro with liver microsomes, hepatocytes and recombinantly expressed enzymes
      analyzed by LC/MS.
AB  - Liver microsome and hepatocyte-mediated biotransformation of three oral
      antileishmanial 2-substituted quinolines were investigated. One quinoline
      contains an n-propyl group (1) and the other a propenyl chain functionalized at
      the gamma position either by a nitrile (2) or an alcohol (3). The different
      isoforms of rat cytochrome P450 responsible for biotransformation of 1 were also
      investigated. Compounds 2 and 3 mainly reacted with glutathione, preventing
      further metabolism. Compound 3 however, the reaction being reversible, could be
      released from glutathione and take alternative reaction pathways. Microsomal
      incubations of 1 mainly led to hydroxylation of the side chain, involving many
      cytochromes, predominantly CYP2B1, CYP2A6 and CYP1A1 (at more than 80%). In
      contrary, minor metabolites hydroxylated on the quinoline ring involved a few
      cytochromes. The hydroxylated products of 1 were conjugated with glucuronic acid
      in rat hepatocyte incubations.

PMID- 17434250
TI  - Small-for-gestational-age fetuses with normal umbilical artery Doppler have
      suboptimal perinatal and neurodevelopmental outcome.
AB  - OBJECTIVE: To evaluate the perinatal and neurodevelopmental outcome of small-for
      gestational-age fetuses with normal umbilical artery Doppler managed expectantly
      during pregnancy and delivery. STUDY DESIGN: Perinatal and neurodevelopmental
      outcome was assessed from a cohort of singleton small-for-gestational-age fetuses
      with normal umbilical artery Doppler and normally grown controls matched by
      gestational age at delivery, parity and parental socio-economic level.
      Neurodevelopmental outcome was prospectively evaluated by means of the 24-month
      Age&Stage Questionnaire (ASQ). RESULTS: A total of 129 small-for-gestational-age
      fetuses and 259 controls were included. Small-for-gestational-age fetuses had a
      higher risk for neonatal intensive care unit admission (15.5% versus 3.9%;
      p<0.001) and significant neonatal morbidity (2.3% versus 0%; p=0.04) than
      controls. At 24-months, these fetuses showed significantly lower
      neurodevelopmental centile in the problem solving (42.8 versus 52.1; p=0.001) and
      personal-social (44.4 versus 54.6; p<0.001) areas than controls. CONCLUSION:
      Perinatal and neurodevelopmental outcome in small-for-gestational-age fetuses
      with normal umbilical artery Doppler is suboptimal, which may challenge the role
      of umbilical artery Doppler to discriminate between normal-SGA and growth
      restricted fetuses.

PMID- 17434251
TI  - Changes in aortic distension waveforms in acute hypoxemia and acidosis: fetal
      lamb study.
AB  - The objective was to investigate the relationship between fetal aortic distension
      waveforms and fetal hypoxemia and/or acidosis. Aortic distension waveforms were
      recorded using an echo-tracking system in nine late-gestation catheterized fetal
      lambs. Under hypoxic conditions induced by inhalation of gas mixture, fetal blood
      pressure and aortic distension waveforms were recorded. Four parameters, namely
      peak systolic and end diastolic diameter, amplitude (DeltaD) and ratio of DeltaD
      to end diastolic diameter (%DeltaD), were obtained, and correlations between
      these parameters and partial arterial oxygen tension (PaO(2)) and pH of fetal
      blood gas were analyzed. These four parameters were compared between the control,
      hypoxemic and asphyxic groups. The DeltaD and %DeltaD were significantly
      correlated with PaO(2) and pH using linear regression analysis. Both the DeltaD
      and %DeltaD decreased significantly, in a stepwise fashion, in the hypoxemic and
      asphyxiated groups compared with controls using repeated measured analysis of
      variance. It was concluded that fetal aortic distension waveforms proved to be a
      useful tool to detect the deterioration in the fetal circulation secondary to
      intrauterine hypoxemia/asphyxia.

PMID- 17434252
TI  - Re: Rufus Cartwright and Linda Cardozo. Transdermal oxybutynin: sticking to the
      facts. Eur urol 2007;51:907-14.

PMID- 17434253
TI  - Editorial comment on: P0 stage at radical cystectomy for bladder cancer is
      associated with improved outcome independent of traditional clinical risk
      factors.

PMID- 17434254
TI  - P0 stage at radical cystectomy for bladder cancer is associated with improved
      outcome independent of traditional clinical risk factors.
AB  - OBJECTIVES: Final pathologic specimen free of detectable disease (P0) is not
      uncommon in patients undergoing cystectomy for bladder cancer, especially in the
      era of neoadjuvant chemotherapy. To improve our understanding of its significance
      in a contemporary series, we performed an outcomes analysis of this cohort of
      patients. METHODS: Over the last 15 yr, 1104 patients with bladder cancer
      underwent radical cystectomy at our institution. Of these, 120 (11%) were pT0N0M0
      (P0) in the surgical specimen and form the basis of this report. Survival data
      were estimated by method of Kaplan and Meier, with Cox proportional hazards
      regression model used to evaluate associations between survival and variables
      studied. RESULTS: Clinical stages were cT1, 21 patients; cT2, 65; cT3b, 20; cT4a,
      11; and cT4b, 3. The 5-yr estimates of overall (OS), disease-specific (DSS), and
      recurrence-free survival (RFS) rates were 84%, 88%, and 84%, respectively. With
      mean follow-up of 43 mo, 11 patients developed recurrences, 9 of whom died of
      disease. Median time to recurrence was 7.7 mo (range: 2.2-45 mo). On multivariate
      analysis, presence of lymphovascular invasion and concomitant carcinoma in situ
      on the transurethral resection of the bladder tumor specimen were the only
      significant prognostic factors associated with shorter OS (p = 0.04) and RFS (p =
      0.049), respectively. Notably, patients who received preoperative chemotherapy (n
      = 77) had 5-yr survival rates similar to those of patients who did not.
      CONCLUSION: Although patients who are P0 at cystectomy have a good prognosis, not
      all can be considered cured. The favorable prognosis conferred by a P0 state
      appears to be independent of whether this is achieved by neoadjuvant chemotherapy
      or by thorough transurethral resection before cystectomy.

PMID- 17434255
TI  - Editorial comment on: P0 stage at radical cystectomy for bladder cancer is
      associated with improved outcome independent of traditional clinical risk
      factors.

PMID- 17434256
TI  - Molecular characterization of prepro-orexin in Atlantic cod (Gadus morhua):
      cloning, localization, developmental profile and role in food intake regulation.
AB  - A full-length cDNA encoding for prepro-orexin (prepro-OX) was cloned from
      Atlantic cod (Gadus morhua) hypothalamus using reverse transcription and rapid
      amplification of cDNA ends (RACE). The 143 amino acids (aa) prepro-OX contains a
      38 aa signal peptide, a 50 aa orexin-A peptide and a 29 aa orexin-B peptide. Semi
      quantitative RT-PCR shows that prepro-OX mRNA is present in brain and pituitary
      and in peripheral tissues, including gill, spleen, stomach and gut. Within the
      brain, high expression levels are seen in the hypothalamus. During development,
      prepro-OX is expressed from the cleavage stage up to the hatched larvae. Slot
      blot analysis shows that prepro-OX expression levels are higher in fish fed low
      (0.2% BW) and medium (0.8% BW) rations than in fish fed high rations (1.5% BW).
      Fish fed low and medium rations also display periprandial changes in prepro-OX
      expression, with higher expression levels at meal time (0 h) compared to 2h
      before and 2h after feeding. Our results suggest that orexins might be involved
      in development and feeding regulation in Atlantic cod.

PMID- 17434258
TI  - Cadmium distribution in sediment profiles of the six main rivers in southern
      Taiwan.
AB  - Dynamic cadmium distribution has been studied in six main rivers flowing through
      the largest, most highly developed and polluted area of southern Taiwan. Sediment
      profile samples were also analyzed for Cu, Cr, Zn, Ni, Pb, Co, Mn, Fe,
      carbonates, Mn-oxides, Fe-oxides and organic matter in order to characterize the
      geochemical environment and to identify the pollutant sources. Higher Cd
      concentrations (about 3.5 mg/kg) at depths of 0-10 cm have been detected in the
      samples of Yenshui, Ell-ren and Potzu rivers, associated to the history of
      industrial activity in their catchments. According to the linear correlation
      coefficient (r) between Cd and the geochemical components, carbonates are the
      primary Cd binding phase in the Ell-ren river (r=0.85), and Cd comes from the
      same pollutant sources of those containing Cr, Ni, Cu and Zn (r>0.80). Cadmium
      concentration in the Potzu and Peikang river sediments is probably due to waste
      deposits rich in Cr and Cu (0.54<r<0.65). In the case of the Yenshui river, there
      is only a weak indication that cadmium derives from waste material containing Cr,
      Ni, Cu, Zn, and Pb (r around 0.40). On the other hand, in the Tsengwen and
      Chishui sediments cadmium concentrations seem to represent natural background.
      Generally, the Ell-ren and Yenshui rivers show strong heavy metal pollution,
      while no important heavy metal contamination has been found in the Tsengwen,
      Potzu, Chishui, and Peikang rivers.

PMID- 17434257
TI  - Vasoactive intestinal peptide induces cyclooxygenase-2 expression through nuclear
      factor-kappaB in human prostate cell lines Differential time-dependent responses
      in cancer progression.
AB  - The effect of vasoactive intestinal peptide (VIP) on cyclooxygenase-2 (COX-2)
      expression was analyzed in human prostate non-neoplastic (RWPE-1) as well as
      cancer androgen-dependent (LNCaP) and independent (PC3) cells. The three cell
      lines expressed VIP mRNA and VIP peptide, as measured by RT-PCR and
      immunochemistry, which supports an autocrine/paracrine action of VIP in the
      prostate gland. VIP levels were progressively higher from non-neoplastic to
      androgen-dependent and independent cells. Real-time RT-PCR and Western-blotting
      showed that VIP stimulated both COX-2 mRNA and protein expression in a faster
      manner as prostate cancer stage progressed (i.e. RWPE1<LNCaP<PC3 cells).
      Furthermore, VIP induced higher levels of COX-2 protein expression in cancer
      cells as compared with non-neoplastic cells. The anti-inflammatory agent curcumin
      blocked VIP-induced COX-2 expression in all cell lines studied supporting the
      involvement of nuclear factor-kappaB (NFkappaB) in such a response. In fact, VIP
      increased the translocation of the NFkappaB p50 subunit to the nucleus and the
      binding of the active form to its target gene promoter, as measured by Western
      blotting and ELISA, respectively. VIP provoked faster responses according to the
      most aggressive status in cancer progression (androgen-independent situation).
      These results together with the existence of two NFkappaB sites in the COX-2 gene
      promoter together suggest that COX-2 may be a target for VIP in prostate cancer
      progression. On the other hand, VIP could be a proinflammatory cytokine acting
      through the NFkappaB/COX-2 system.

PMID- 17434259
TI  - Bio-treatment of oily sludge: the contribution of amendment material to the
      content of target contaminants, and the biodegradation dynamics.
AB  - The objective was to investigate the aerobic biodegradation of oily sludge
      generated by a flotation-flocculation unit (FFU) of an oil refinery wastewater
      treatment plant. Four 1m(3) pilot bioreactors with controlled air-flow were
      filled with FFU sludge mixed with one of the following amendments: sand (M1);
      matured oil compost (M2); kitchen waste compost (M3) and shredded waste wood
      (M4). The variables monitored were: pH, total petroleum hydrocarbons (TPHs),
      polycyclic aromatic hydrocarbons (PAHs), total carbon (C(tot)), total nitrogen
      (N(tot)) and total phosphorus (P(tot)). The reduction of TPH based on mass
      balance in M1, M2, M3 and M4 after 373 days of treatment was 62, 51, 74 and 49%;
      the reduction of PAHs was 97%, +13% (increase), 92 and 88%, respectively. The
      following mechanisms alone or in combination might explain the results: (i) most
      organics added with amendments biodegrade faster than most petroleum
      hydrocarbons, resulting in a relative increase in concentration of these
      recalcitrant contaminants; (ii) some amendments result in increased amounts of
      TPH and PAHs to be degraded in the mixture; (iii) sorption-desorption mechanisms
      involving hydrophobic compounds in the organic matrix reduce bioavailability,
      biodegradability and eventually extractability; (iv) mixture heterogeneity
      affecting sampling. Total contaminant mass reduction seems to be a better
      parameter than concentration to assess degradation efficiency in mixtures with
      high content of biodegradable amendments.

PMID- 17434260
TI  - A method for preparing ferric activated carbon composites adsorbents to remove
      arsenic from drinking water.
AB  - Iron oxide/activated carbon (FeO/AC) composite adsorbent material, which was used
      to modify the coal-based activated carbon (AC) 12 x 40, was prepared by the
      special ferric oxide microcrystal in this study. This composite can be used as
      the adsorbent to remove arsenic from drinking water, and Langmuir isotherm
      adsorption equation well describes the experimental adsorption isotherms. Then,
      the arsenic desorption can subsequently be separated from the medium by using a
      1% aqueous NaOH solution. The apparent characters and physical chemistry
      performances of FeO/AC composite were investigated by X-ray diffraction (XRD),
      nitrogen adsorption, scanning electron microscopy (SEM) and X-ray photoelectron
      spectroscopy (XPS). Batch and column adsorption experiments were carried out to
      investigate and compare the arsenic removal capability of the prepared FeO/AC
      composite material and virgin activated carbon. It can be concluded that: (1) the
      main phase present in this composite are magnetite (Fe(3)O(4)), maghemite (gamma
      Fe(2)O(3)), hematite (alpha-Fe(2)O(3)) and goethite (alpha-FeO(OH)); (2) the
      presence of iron oxides did not significantly affect the surface area or the pore
      structure of the activated carbon; (3) the comparisons between the adsorption
      isotherms of arsenic from aqueous solution onto the composite and virgin
      activated carbon showed that the FeO/AC composite behave an excellent capacity of
      adsorption arsenic than the virgin activated carbon; (4) column adsorption
      experiments with FeO/AC composite adsorbent showed that the arsenic could be
      removed to below 0.01 mg/L within 1250 mL empty bed volume when influent
      concentration was 0.5mg/L.

PMID- 17434261
TI  - New approach for predicting melting point of carbocyclic nitroaromatic compounds.
AB  - A simple correlation has been introduced to estimate melting point of carbocyclic
      nitroaromatic compounds. The methodology assumes that melting point of a
      carbocyclic nitroaromatic compound with general formula C(a)H(b)N(c)O(d) can be
      expressed as a function of the number of hydrogen and nitrogen atoms as well as
      the contribution of some specific functional groups and the existence of ortho or
      para isomers in disubstituted benzene ring. Predicted melting points using the
      method described herein and group contribution method of Joback and Reid [K.G.
      Joback, R.C. Reid, Chem. Eng. Commun. 57 (1987) 233] have the average deviation
      of 5.0 and 37.6%, respectively, for 60 carbocyclic nitroaromatic compounds. The
      proposed new method clearly exhibits a much better accuracy.

PMID- 17434262
TI  - Degradation of phenol and TCE using suspended and chitosan-bead immobilized
      Pseudomonas putida.
AB  - The degradability of phenol and trichloroethene (TCE) by Pseudomonas putida BCRC
      14349 in both suspended culture and immobilized culture systems are investigated.
      Chitosan beads at a size of about 1-2mm were employed to encapsulate the P.
      putida cells, becoming an immobilized culture system. The phenol concentration
      was controlled at 100 mg/L, and that of TCE was studied from 0.2 to 20 mg/L. The
      pH, between 6.7 and 10, did not affect the degradation of either phenol or TCE in
      the suspended culture system. However, it was found to be an important factor in
      the immobilized culture system in which the only significant degradation was
      observed at pH >8. This may be linked to the surface properties of the chitosan
      beads and its influence on the activity of the bacteria. The transfer yield of
      TCE on a phenol basis was almost the same for the suspended and immobilized
      cultures (0.032 mg TCE/mg phenol), except that these yields occurred at different
      TCE concentrations. The transfer yield at a higher TCE concentration for the
      immobilized system suggested that the cells immobilized in carriers can be
      protected from harsh environmental conditions. For kinetic rate interpretation,
      the Monod equation was employed to describe the degradation rates of phenol,
      while the Haldane's equation was used for TCE degradation. Based on the kinetic
      parameters obtained from the two equations, the rate for the immobilized culture
      systems was only about 1/6 to that of the suspended culture system for phenol
      degradation, and was about 1/2 for TCE degradation. The slower kinetics observed
      for the immobilized culture systems was probably due to the slow diffusion of
      substrate molecules into the beads. However, compared with the suspended
      cultures, the immobilized cultures may tolerate a higher TCE concentration as
      much less inhibition was observed and the transfer yield occurred at a higher TCE
      concentration.

PMID- 17434263
TI  - Prediction of impact sensitivity of nitroaliphatic, nitroaliphatic containing
      other functional groups and nitrate explosives.
AB  - This paper describes a new method for prediction of impact sensitivity of
      nitroaliphatic, nitroaliphatic containing other functional groups and nitrate
      explosives. The new procedure is based on some structural parameters of
      C(a)H(b)N(c)O(d) explosives. Three essential parameters would be needed in this
      scheme which contain a+b/2-d and the number of nitrogens as well as the number of
      RC(NO(2))(2)CH(2) structural parameters attached to oxygen of carboxylate
      functional groups where R is alkyl groups. The results are compared with
      experimental data and some empirical correlations. Predicted impact sensitivities
      for 58 explosives have a root mean square (rms) of deviation from experiment of
      27 cm, which show good agreement with respect to measured values as compared to
      previous empirical models.

PMID- 17434264
TI  - TDP-43 gene analysis in frontotemporal lobar degeneration.
AB  - It has recently been established that the ubiquitinated neuronal inclusions and
      neurites observed in frontotemporal lobar degeneration (FTLD) contain the TAR DNA
      binding protein, TDP-43. It is not uncommon for genetic variation of genes that
      encode proteins that accumulate in neurodegenerative conditions to increase risk
      for disease. We therefore examined whether variation of the TDP-43 locus was
      associated with an increased risk of disease in the Manchester FTLD cohort. We
      found no evidence of TDP-43 variation increasing risk for FTLD in this cohort.
      These data suggest that TDP-43 accumulation is a consequence of the disease
      process underlying FTLD.

PMID- 17434265
TI  - Psychosocial issues in adolescents with cancer.
AB  - Cancer in adolescents is uncommon and when it occurs raises a number of unique
      challenges for both the patient and their families. Adolescence is a period of
      time of significant physical and emotional changes and a diagnosis of cancer
      during this time has a major impact on their psychological and physical
      development. In this review we will look at the psychosocial issues facing
      adolescents who have cancer. We will address adolescent development, issues
      related to informed consent and assent, initial responses to the diagnosis of
      cancer, quality of life and the experience of the adolescent with cancer,
      psychological adjustment, support systems, body image issues, sexuality,
      education, hope, and treatment compliance.

PMID- 17434266
TI  - Effects of extracellular pH on neuronal calcium channel activation.
AB  - Previous studies have shown that extracellular pH (pHo) alters gating and
      permeation properties of cardiac L- and T-type channels. However, a comprehensive
      study investigating the effects of pHo on all other voltage-gated calcium
      channels is lacking. Here, we report the effects of pHo on activation parameters
      slope factor (S), half-activation potential (Va), reversal potential (Erev), and
      maximum slope conductance (Gmax) of the nine known neuronal voltage-gated calcium
      channels transiently expressed in tsA-201 cells. In all cases, acidification of
      the extracellular bathing solution results in a depolarizing shift in the
      activation curve and reduction in peak current amplitudes. Relative to a
      physiological pHo of 7.25, statistically significant depolarizing shifts in Va
      were observed for all channels at pHo 7.00 except Cav1.3 and 3.2, which showed
      significant shifts at pHo 6.75 and below. All channels displayed significant
      reductions in Gmax relative to pHo 7.25 at pHo 7.00 except Cav1.2, 2.1, and 3.1
      which required acidification to pHo 6.75. Upon acidification Cav3 channels
      displayed the largest changes in Vas and exhibited the largest reduction in Gmax
      compared with other channel subtypes. Taken together, these results suggest that
      significant modulation of calcium channel currents can occur with changes in pHo.
      Acidification of the external solution did not produce significant shifts in
      observed Erevs or blockade of outward currents for any of the nine channel
      subtypes. Finally, we tested a simple Woodhull-type model of current block by
      assuming blockade of the pore by a single proton. In all cases, the amount of
      blockade observed could not be explained in these simple terms, suggesting that
      proton modulation is more complicated, involving more than one site or gating
      modification as has been previously described for cardiac L- and T-type channels.

PMID- 17434267
TI  - Perceived risk, peer influences, and injection partner type predict receptive
      syringe sharing among young adult injection drug users in five U.S. cities.
AB  - OBJECTIVES: This study examined risk factors for receptive syringe sharing (RSS)
      during illicit drug injection by persons 15-30 years old in five U.S. cities.
      METHODS: Participants were recruited through street outreach and respondent
      driven referrals in Baltimore, Chicago, Los Angeles, New York, and Seattle
      between May 2002 and January 2004. Surveys of drug use, sexual behaviors, and
      correlates were administered through audio computer-assisted self-interviews at
      baseline and, for the subset of participants who enrolled in an HIV/HCV
      prevention intervention trial, at 3-months and 6-months post-baseline. The
      proportions of injections involving RSS at baseline and at follow-up were used as
      outcomes in multivariate models that adjusted for intervention effects. RESULTS:
      At baseline, 54% of 3128 participants reported RSS in the past 3 months. RSS
      decreased to 21% at 6-months post-baseline for the combined trial arms.
      Participants were more likely to report RSS if they perceived that their peers
      were not against RSS and if they injected with sex partners. Lower levels of
      perceived risk of infection with HIV (baseline, p<.001) or HCV (follow-up,
      p<.001) through RSS were also significant predictors of greater RSS. CONCLUSIONS:
      Perceived risks, peer influences, and type of injection partner were robust
      predictors of RSS. Perceived risks and peer influences are particularly amenable
      to intervention efforts that may prevent RSS in this age group.

PMID- 17434268
TI  - Characterization of the porcine multicopy ribosomal protein SA/37-kDa laminin
      receptor gene family.
AB  - Prions represent a new class of infectious agents. The pathogenic prion protein
      (PrPSc) is known as the trigger of bovine transmissible spongiform encephalopathy
      (TSE). By contrast, an oral transmission of PrPSc and an ensuing infection seems
      to be blocked in non-ruminants such as pigs. Several investigations postulate
      that the ribosomal protein SA (RPSA) previously named 37-kDa laminin receptor
      precursor (LRP)/67-kDa laminin receptor (LR) is the candidate for binding and
      internalization of externally added cellular prion protein in the gut. We
      isolated a porcine ribosomal protein SA cDNA that consists of 1064 bp with an
      open reading frame of 885 bp encoding a 295 aa protein. The alignment of
      vertebrate ribosomal protein SA sequences displayed interspecies differences
      between cattle and pigs at positions 241 and 272 in the putative indirect PrP
      interaction site (aa 180-285) on RPSA. A PAC library screen revealed the
      existence of two processed ribosomal protein SA pseudogenes (RPSAP1 and RPSAP3)
      and of one non-processed pseudogene (RPSAP2). The pseudogenes have been assigned
      to SSC6 and SSC1 by hybrid panel analyses and FISH. Compared with the porcine
      cDNA 3, 7, and 13 insdels, 36, 25, and 57 single nucleotide exchanges and 6, 10,
      and 8 premature stop codons have been deciphered for RPSAP1, RPSAP2, and RPSAP3.
      In the 5', 3', and intron like regions, 2 (RPSAP1), 10 (RPSAP2), and 4 (RPSAP3)
      repeats have been detected. Basically, the repeats belong to one of the
      class/family LINE/L1, SINE/tRNA-Glu and DNA/MER1_type. We conclude that the pig
      genome contains multiple copies of the RPSA sequence probably as a consequence to
      maintain the multifunctionality of the mature protein.

PMID- 17434269
TI  - Luteinizing hormone (LH) isoforms in ruminants: characterization and
      physiological relevance.
AB  - The luteinizing hormone (LH) is secreted in multiple molecular forms into the
      blood stream; however, few studies have characterized the pattern of the
      circulating LH isoforms in domestic animals during different physiological
      stages. Most of the publications are related to the pattern of isoforms present
      in the anterior pituitary gland. This review includes recent evidence concerning
      the distribution of LH isoforms in the pituitary gland and serum in ruminants.
      The structural heterogeneity of this hormone is emphasized, including the
      glycosylation biosynthetic pathway, as well as the different proportions of
      oligosaccharides that confer particular functional characteristics to the
      heterodimer. Evidence for a regulating role of GnRH, estradiol and progesterone
      is discussed.

PMID- 17434270
TI  - Combinatorial design of passive drug delivery platforms.
AB  - We introduce a novel computational approach to designing passive drug delivery
      systems based on porous materials such as hydrogels. Our approach uses three
      tools: a method to establish the exact release pattern from all possible loading
      sites inside a given hydrogel; a method to generate a large number of hydrogel
      structures to be tested numerically, and finally an optimization algorithm which
      leads to the selection of optimal hydrogel structures. Using this approach, we
      show that controlled release curves can be obtained by using a genetic algorithm
      for the optimization step. Strategies to generalize this approach to other
      systems are also discussed.

PMID- 17434272
TI  - Effects of curcumin in treatment of experimental pulmonary fibrosis: a comparison
      with hydrocortisone.
AB  - To compare curcumin with hydrocortisone for treating bleomycin-induced pulmonary
      fibrosis (BLMPF), four groups of rats were injected with 1.5 mg/kg bleomycin
      intratracheally. Then the Group HC rats were treated with three injections of
      2mg/kg hydrocortisone i.p.; Group CH and CL rats, respectively, were orally given
      500 or 250 mg/kg curcumin daily; and Group PC rats were given deionized water
      alone. After 28 days of treatment, lung samples were examined by H-E staining,
      Masson's staining and immunohistochemical analyses and pulmonary type I collagen
      (Col-I), inducible nitric oxide synthetase (iNOS) and transforming growth factor
      beta1 (TGF-beta1) were determined by Western blotting and real-time RT PCR
      analyses. The results showed that (1) Group PC rats had histopathological
      characteristics of BLMPF with significant increase in their protein/mRNA
      expressions of Col-I (+114%/+173%), iNOS (+146%/+523%) and TGF-beta1
      (+476%/+527%) (P<0.01); (2) in Group HC, CH and CL rats, protein/mRNA expressions
      of Col-I (-39%/-52%, -31%/-57%, -33%/-58%), iNOS (-31%/-51%, -31%/-79%, -31%/
      47%) and TGF-beta1 (-64%/-78%, -75%/-74%, -81%/-79%) were significantly lower
      than Group PC (P<0.05); (3) except for levels of TGF-beta1 protein, there was no
      significant difference among Group CH, CL and HC rats (P>0.05). It suggests that
      curcumin may play a similar role as hydrocortisone in preventing BLMPF.

PMID- 17434273
TI  - Injuries to law enforcement officers: the backface signature injury.
AB  - In today's law enforcement community, one of the most vital tools an officer can
      possess is personal body armor. However, a recent Department of Justice
      investigation has raised important questions regarding the protection actually
      afforded officers through the use of personal body armor, and the current test
      methods used to assess the armor. Test results show that most Zylon-containing
      vests showed deformations in excess of the 0101.04 Standard's 44 mm backface
      signature limit. Such increased deformation can lead to serious injuries,
      including backface signature injuries, which have occurred in the field. Although
      the vest is successful in containing the round, it is not effectively dissipating
      the energy enough to prevent large amounts of vest deformation at the area of
      impact. Therefore, open, penetrating wounds occur even though the bullet did not
      penetrate the vest. The objective of the current study was to further define the
      backface signature injury through the use of case studies and laboratory
      experiments. Following the case study investigation, backface signature testing
      was conducted using a clay medium based on the NIJ 0101.04 Standard. The final
      component of this research involved the use of post-mortem human specimens (PMHS)
      for further investigation of the backface signature injury. Although the
      underlying cause of backface signature injuries is unknown, energy density is
      likely to play a role in the mechanism. Energy density (E/a) is defined as the
      energy per unit area and has been previously used in less lethal skin penetration
      research. Further research into the underlying causes of backface signature
      injuries is necessary. In addition to armor testing, the study of law enforcement
      personnel who have been shot while wearing soft body armor is also a valuable
      tool for determining the effectiveness of certification standards. Finally, it is
      important for medical personnel to recognize the backface signature injury and
      document this as a type of injury separate from blunt trauma or penetrating
      trauma behind armor injuries. Detailed knowledge of the injury, including the
      depth of the wound, would be beneficial to the scientific community.

PMID- 17434274
TI  - The U.S. Mandatory Guidelines for Federal Workplace Drug Testing Programs:
      current status and future considerations.
AB  - The U.S. Department of Health and Human Services (HHS) drug testing standards
      were published in 1988 and revised in 1994, 1998, and 2004. In 2004, significant
      revisions defining, standardizing, and requiring specimen validity testing on
      Federal employee donor urine specimens were included. In a separate notice, HHS
      proposed to establish scientific and technical guidelines for the Federal
      Workplace Drug Testing Program to: (1) permit laboratory testing of hair, oral
      fluid, and sweat patch specimens in addition to urine specimens for marijuana,
      cocaine, phencyclidine, opiates (with focus on heroin), and amphetamines
      [including methylenedioxymethamphetamine (MDMA), methylenedioxyethamphetamine
      (MDEA), methylenedioxyamphetamine (MDA)]; (2) permit use of on-site point of
      collection test (POCT) devices to test urine and oral fluid at collection sites;
      (3) permit use of instrumented initial test (screening only) facilities [IITF] to
      quickly identify negative specimens; and (4) add training requirement for
      collectors, on-site testers, and MROs. This proposal was published in the Federal
      Register on 13 April 2004, with a 90-day public comment period. The Substance
      Abuse and Mental Health Services Administration, HHS, reviewed those comments and
      is preparing the Final Notice that will define the requirements for such testing,
      including: specimen collection procedures, custody and control procedures that
      ensure donor specimen identity and integrity, testing facility, initial and
      confirmatory test cutoff concentrations, analytical testing methods, result
      review and reporting, evaluation of alternative medical explanations for presence
      of drug or metabolite in the donor's specimen, and laboratory certification
      issues. Voluntary pilot performance testing (PT) programs for each specimen type
      are on-going since April 2000 to determine how to prepare PT materials for
      specimens other than urine to evaluate laboratories' ability to routinely achieve
      accuracy and precision required. Certification programs will be developed using
      the current urine drug testing National Laboratory Certification Program model.
      The addition of accurate and reliable workplace drug testing using hair, oral
      fluid, and sweat patch specimens will complement urine drug testing, and aid in
      combating industries devoted to suborning drug testing through adulteration,
      substitution, and dilution. For example, hair testing may detect chronic drug use
      for up to 90 days and be useful in pre-employment situations; oral fluid testing
      may detect drug use in past hours and be useful in post-accident situations;
      sweat patch testing may be useful in follow-up drug testing and treatment
      programs; POCTs and IITFs may be most useful for quickly identifying specimens
      that are negative for drugs and indicate that the specimen is valid.

PMID- 17434275
TI  - New technology and new initiatives in U.S. workplace testing.
AB  - A current perspective of workplace drug testing in the USA is presented covering
      three major issue areas: (1) epidemiology, (2) new technology and (3) initiatives
      to reach out and assist small business. First, national illegal drug-use self
      reported survey data is compared with national laboratory drug testing results,
      illustrating a number of inconsistencies. During the 17-year period (1988-2004)
      the number of laboratory positive test results has decreased by 66% while during
      the same period self-reported drug-use has increased by 30%. The lack of
      concurrence between lab results and self-report surveys are examined in light of
      the typical panel of drugs being tested in U.S. laboratories, the increased
      specificity of immunoassay screening tests, and the critical issues of
      adulteration and substitution. Second, a brief review of the state-of-the-science
      in rapid point-of-collection (POCT) oral fluid drug-testing devices is presented
      along with some device evaluation findings. In general the window of drug
      detection in oral fluid is measured in hours. Most of the available oral fluid
      POCT devices can detect methamphetamine and amphetamines and opiates very well.
      The ability to detect cocaine appears to vary significantly across devices, while
      the ability to detect cannabis use is generally poor across all devices. Finally,
      efforts to reach out and assist small businesses in the development of workplace
      anti-drug programs are discussed in the context of increasing workplace programs
      in the European Union.

PMID- 17434276
TI  - A review of the literature on the aging adult skull and face: implications for
      forensic science research and applications.
AB  - This paper is a summary of findings of adult age-related craniofacial
      morphological changes. Our aims are two-fold: (1) through a review of the
      literature we address the factors influencing craniofacial aging, and (2) the
      general ways in which a head and face age in adulthood. We present findings on
      environmental and innate influences on face aging, facial soft tissue age
      changes, and bony changes in the craniofacial and dentoalveolar skeleton. We then
      briefly address the relevance of this information to forensic science research
      and applications, such as the development of computer facial age-progression and
      face recognition technologies, and contributions to forensic sketch artistry.

PMID- 17434277
TI  - Treatments with midazolam and lidocaine for status epilepticus in neonates.
AB  - Status epilepticus (SE) occurs in children of all ages. Recent epidemiologic
      investigations of SE show heightened morbidity and mortality in newborns and
      young infants. However, the existing definition of SE in newborns is not precise
      and not easily applied in clinical investigations or in clinical practice. To
      evaluate the underlying conditions, clinical features and treatment of SE in
      neonates in Japan, a retrospective multi-center study was performed. In the
      initial investigation, questionnaires were sent to pediatric neurologists in 194
      neonatal intensive care units of university hospitals, children's hospitals, and
      general hospitals throughout in Japan. The questionnaires sought information on
      the background of each case, types of seizures, etiology of SE, treatments,
      results and adverse effects of treatment for patients less than 1 week old who
      had prolonged or frequently repeated seizures lasting more than 15 min and who
      are refractory to treatment with conventional anticonvulsants, such as diazepam
      (DZP), phenobarbital (PB) or phenytoin (PHT). As a secondary investigation, 65
      cases from nine institutes, which completely fulfilled these criteria and were
      treated with midazolam (MDL) or lidocaine (Lid) to stop seizures were examined
      more fully. Subtle seizure and generalized tonic-clonic seizure were the most
      frequent seizure types. Neonatal SE was most frequently associated with hypoxic
      ischemic encephalopathy, followed by intraventricular hemorrhage, central nervous
      system infections, and cerebral infarction. The final treatment outcome was
      available for 72.7% and 81.3% of MDL- and Lid-treated patients, respectively.
      Adverse effects of MDL and Lid were identified in 7.3% and 6.3% of patients,
      respectively. To reveal electroclinical seizures, clinical seizures without ictal
      discharge or other non-epileptic movements in neonates was important for
      appropriate treatment. MDL and Lid were useful drugs for the treatment of
      neonatal SE.

PMID- 17434278
TI  - [Changing social disparities and mortality in France (1968-1996): cause of death
      analysis by educational level].
AB  - BACKGROUND: Little information is available on temporal trend in socioeconomic
      inequalities in cause of death mortality in France. The aim of this paper was to
      study educational differences in mortality in France by cause of death and their
      temporal trend. METHODS: We used a representative sample of 1% of the French
      population and compared four periods (1968-1974, 1975-1981, 1982-1988, 1990
      1996). Causes of death were obtained by direct linkage with the French national
      death registry. Education was measured at the beginning of each period, and
      educational disparities in mortality were studied among men and women aged 30-64
      at the beginning of each period. Analyses were conducted for all deaths and for
      the following causes of death: all cancers, lung cancer (among men), upper
      aerodigestive tract cancers (among men), breast cancer (among women), colorectal
      cancer, other cancers, cardiovascular diseases, ischaemic heart diseases,
      cerebrovascular diseases, other cardiovascular diseases, external causes, other
      causes of death. Socioeconomic inequalities were quantified with relative risks
      and relative indices of inequality. The relative indices of inequality measures
      socioeconomic inequalities across the population and can be interpreted as the
      ratio of mortality rates of those with the lowest to those with the highest
      socioeconomic status. RESULTS: Analyses showed an increase in educational
      differences in all cause mortality among men (the relative indices of inequality
      increased from 1.96 to 2.77 from the first to the last period) and among women
      (the relative indices of inequality increased from 1.87 to 2.53). Socioeconomic
      inequalities increased for all cause of death studied among women, and for cancer
      and cardiovascular diseases among men. The contribution of cancer mortality to
      difference in overall mortality between the lowest and the highest levels of
      education increased strongly over the whole study period, especially among women.
      CONCLUSION: This study shows that large socioeconomic inequalities in mortality
      are observed in France, and that they increase over time among men and women.

PMID- 17434279
TI  - [Prevention practices of primary health care physicians in Switzerland in the
      context of the HIV/Aids epidemic: changes between 1990 and 2002].
AB  - BACKGROUND: Individual preventive counseling offered to the general public by
      private doctors working in primary health care is an essential component of the
      Swiss National Aids Prevention strategy. Surveys were conducted to assess to what
      extent they fulfill this role and how this may have changed over time. METHODS:
      Three cross-sectional surveys were conducted in 1990, 1995, and 2002 by anonymous
      mailed questionnaire in a random sample of primary health care physicians.
      Dimensions of the physicians HIV prevention practices investigated were: practice
      of HIV risk assessment, content and frequency of HIV pretest counseling, and, in
      2002 only, care of patients living with HIV/AIDS. Trends over the 12-year period
      were calculated; logistic regressions were performed to investigate factors
      associated with the frequency of counseling given to HIV positive patients.
      RESULTS: Risk assessment has increased dramatically over the period for certain
      groups of patients (patients requesting contraception, young people and new
      patients). In 2002, routine screening is often or always performed by 93% of
      physicians for intravenous drug patients or patients with a sexually transmitted
      infection; 77% for homosexuals; 76% for patients requesting contraception; 63%
      for young people. It is less frequent in other groups (migrants: 40%;
      separated/divorced patients: 29%). More than half of physicians care for patients
      with HIV. Around two-thirds of physicians regularly discuss with their HIV
      positive patients issues related to patients' professional, social and private
      life. There are few differences among specialties regarding the propensity to
      discuss these topics. CONCLUSION: Prevention activities by primary care
      physicians have increased in the last decade. Nonetheless, potential for
      increased prevention still exists in some areas of risk assessment and
      counseling.

PMID- 17434280
TI  - [Evaluation of a multifaceted intervention for implementing national guidelines:
      the case of physical restraint in geriatric care].
AB  - BACKGROUND: There is a growing interest in developing guidelines. The French
      Agency for accreditation and Evaluation (Anaes) published in October 2000
      guidelines on the use of restraint in geriatric care settings because in spite of
      the risks this practice remains widespread in that type of care setting. A
      multifaceted intervention was conducted in a Parisian geriatric hospital in order
      to improve the implementation of the published guidelines. An epidemiological
      study was conducted to assess the outcomes of this intervention. METHODS: The
      intervention consisted in distributing educational materials and a specific
      prescription sheet, and in staff training sessions. A time series study was used
      to assess outcomes. The three time points were: before the intervention, just
      after the end of the intervention and one year later. Two dimensions were
      studied: implementation of the guidelines using markers collected from patients'
      charts and restraining practices noted in an observational study of hospitalized
      patients. RESULTS: The results of the study suggest that five recommendations
      were followed better: restraint prescription (8.7 to 57.4%), writing in the
      patient chart the reasons for restraining (3.5 to 35.3%), follow-up prescription,
      assessment of potential benefits and risks for the patient and patient
      information (0% to 19-34%). Nevertheless, the prevalence of restraint and of
      devices employed (around 70%) remained unchanged after the intervention. The
      various outcomes of the intervention might be explained by the guidelines
      themselves, which were variably practical or precise. Moreover, the effect of
      certain factors directly related with the use of restraint, a routine practice
      strongly supported by myths about its efficacy, as well as factors related to
      intervention design may merely have prevented any decrease in the use of
      restraint practices. CONCLUSION: Multifaceted intervention can favour
      implementation of certain national guidelines such as prescribing restraint, but
      can also fail in stimulating the implementation of others such as decreasing the
      prevalence of restraint in geriatric practice. Therefore the next intervention
      should emphasize alternatives to physical restraint practices.

PMID- 17434281
TI  - [Hospital pathway of patients with breast cancer].
AB  - Health care network should promote better quality, equity and care efficacy. On
      the subject of breast cancer, literature has shown inequality in care depending
      on geographical areas and health centres locations. This article illustrates a
      method of analysis of female non in situ non metastatic breast cancer patients
      hospital care pathway, from the 2002 and 2003 Poitou-Charentes' county Diagnosis
      Related Groups (DRG's) data bases. The treatments several phases are described
      along with their combination. The number of chemotherapy and radiotherapy
      sessions per patient are each analysed for comparison between Health Centres,
      Health Centres Status, and in view of the referentials recommendations. Several
      health pathways options are quantified: Mono/pluri Health Centres sites,
      inside/outside a geographical department, inside/outside Poitou-Charentes county.
      Nine hundred and nine patients hospital care pathways are described. Surgery was
      more often partial (66%), with Health Centres variation between 17 and 68%. Among
      the 308 patients who had chemotherapy, 78% received between 4 and 6 sessions,
      with variation per Health Centre between 65 and 90%. Radiotherapy is difficult to
      trace because of the Health Centres non systematic radiotherapy sessions linkage,
      and private Health Centres lack of information (no DRG's). 91% of identified
      radiotherapy benefiting patients had 25 to 35 sessions, in conformation with
      recommendations depending on the surgery performed with Health Centres variation
      ratio between 76 and 96%. Hospital care pathways options between two type of
      treatments were identified. 90% of the hospital care pathways took place in the
      same geographical department, and 30% took place in public Health Centres alone.
      Despite radiotherapy tractability limits, proper DRG's data collection allows the
      description of health pathways between Health Centres and allows health practice
      disparity identification. Using this tool, in accordance with the Cancer Plan,
      can therefore help health networks in evaluating care pathway in cancer and many
      other fields.

PMID- 17434282
TI  - The influence of maternal treadmill running during pregnancy on short-term memory
      and hippocampal cell survival in rat pups.
AB  - Maternal exercise during pregnancy has been suggested to exert the beneficial
      effects on the brain functions of offspring. In the present study, we attempted
      to determine the effects of maternal treadmill running during pregnancy on short
      term memory ability, hippocampal cell survival, and the expression of brain
      derived neurotrophic factor (BDNF) mRNA in rat pups. After confirming pregnancy,
      the pregnant rats were divided into two groups: the control group and the running
      group (n = 6 in each group). Beginning on the 15th day of pregnancy, the pregnant
      rats in the running group were forced to run on a treadmill for 30 min at a mild
      intensity, once a day until delivery. After all the pregnant rats had given
      birth, there were rat pups available for use in this study in each group (n = 15
      in each group). The latency of the step-down avoidance task was used in order to
      evaluate the short-term memory ability of the rat pups on the 28 days after
      birth. Immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU) and reverse
      transcription-polymerase chain reaction (RT-PCR) for BDNF mRNA were performed to
      determine hippocampal neurogenesis and hippocampal BDNF mRNA expression of the
      rat pups on the 29 days after birth, respectively. Our results revealed that
      maternal running during pregnancy resulted in significant increase in the
      expression of BDNF mRNA, enhanced hippocampal cell survival, and improved the
      short-term memory capability of rat pups, as compared to those measured in the
      control group. The findings of our study provide evidence that maternal running
      during gestational period may enhance the brain functions of offspring.

PMID- 17434283
TI  - Interstitial pneumonitis: an exceptional toxicity of hyperthermic intraperitoneal
      mitomycin C.

PMID- 17434284
TI  - [Airway management in a patient with a penetrating cervical wound and an
      expansive haematoma].

PMID- 17434285
TI  - [Screening for biliary atresia and stool color: method of colorimetric scale].
AB  - Biliary atresia is a rare disease, but it is the major cause of neonatal
      cholestasis and the major indication for liver transplantation in children. Kasai
      procedure can restore bile flow and prevent or slow progression of disease in a
      proportion of patients. Data show that the earlier the Kasai procedure is
      performed, the better is the outcome. Therefore, rapid referral to an experienced
      center, for prompt diagnosis and surgery, is strongly recommended. Unfortunately,
      the disease is often detected late and Kasai procedure is performed after 60 days
      of age. In an attempt to achieve earlier diagnosis and better outcome of Kasai
      procedure, we propose to institute routine screening for biliary atresia using a
      stool colorometric scale. This should help to identify earlier children who have
      acholic stools and may have biliary atresia. We postulate that this screening
      method will allow to improve the results of the Kasai procedure and provide
      children with the best chance of survival with their native liver.

PMID- 17434286
TI  - [Follow-up brain imaging after strokes in internal medicine: frequently requested
      but rarely used for diagnosis or treatment].
AB  - OBJECTIVE: To assess the interest of a second computed tomography (CT) scan of
      the brain during hospitalization of stroke patients in an internal medicine
      department and study the characteristics of these patients. METHOD: This
      retrospective study included 110 patients diagnosed with stroke between January
      1, 2002, and August 31, 2004 in an internal medicine department. RESULT: All
      patients had a brain CT scan soon after admission - within three hours, on
      average, of arrival at the hospital; however, the mean delay between the onset of
      symptoms and hospital arrival was 40 hours. Mean hospital stay was 19 days.
      Eighty patients (73%) had at least one more scan. Indications for these scans
      were: no acute cerebral ischemia on the initial image (34%), routine follow-up or
      reason not specified (34%), worsening of neurologic status (15%), before oral
      anticoagulation (5%), to search a tumor (5%), to look for a cause (4%), and
      clinic-radiologic discordance (3%). Only 29% of the indications had any
      diagnostic or therapeutic reason. Among these 80 patients, the repeat brain scan
      resulted in a change in the initial diagnosis for 4 patients (5%) and in a change
      of therapy for 11 (14%). CONCLUSION: In our study, repeat CT imaging was
      frequently ordered in ischemic stroke, despite the not uncommon absence of any
      diagnostic or therapeutic reasons. To optimize the use of medical resources and
      avoid unnecessary imaging, it would be useful to identify subgroups of patients
      for whom repeat imaging might be of interest.

PMID- 17434287
TI  - The sensitivity and specificity of flashbacks and nightmares to trauma.
AB  - Traumatic events are commonly re-experienced by trauma survivors through
      nightmares and flashbacks. The current study examined the relative sensitivity
      and specificity of these two forms of re-experiencing trauma in female survivors
      of rape. The frequency of nightmares and flashbacks were assessed using the
      Nightmare Frequency Questionnaire (NFQ) and the Flashback Frequency Questionnaire
      (FFQ), respectively. The FFQ was developed for this study and is designed to
      assess the frequency and occurrence of flashbacks in trauma survivors. The NFQ,
      FFQ and a variety of other measures were completed by 34 female survivors of rape
      and 28 female control participants. Results provided support for the construct
      and criterion validity of the FFQ, and demonstrated that flashbacks are more
      sensitive and specific indicators of the presence of trauma than are nightmares.

PMID- 17434288
TI  - Children's interpretation and avoidant response biases in response to non-salient
      and salient situations: relationships with mothers' threat perception and coping
      expectations.
AB  - This study examined the effect of situation salience on interpretation and
      avoidant response biases in clinically anxious and non-clinical children. The
      relationship between mothers' threat perception and expectations of their
      children's coping, and children's threat perception and coping expectations was
      also assessed. Forty clinically anxious and 40 non-clinical children (ages 7-14)
      participated with their mothers. In response to hypothetical situations, children
      described their likely thoughts and actions; mothers listed a typical child's
      thoughts and what their child would do. Consistent with information processing
      theories of anxiety, anxious children displayed amplified cognitive biases in
      response to personally salient situations, compared to non-clinical children.
      Mothers of anxious children had lower expectations for their children's coping
      than mothers of non-anxious children, mirroring differences between the groups of
      children. Mothers' expectations of their children's coping predicted children's
      coping expectations in non-salient and salient situations and threat perception
      in salient situations. Implications of findings are discussed.

PMID- 17434290
TI  - Maturational arrest of thymocyte development is caused by a deletion in the
      receptor-like protein tyrosine phosphatase kappa gene in LEC rats.
AB  - The Long-Evans Cinnamon (LEC) rat has a spontaneous mutation, T helper
      immunodeficiency (thid), which causes a markedly reduced CD4(+) thymocyte
      population. Here we positionally clone the locus and identify a deletion in the
      gene encoding a receptor-like protein tyrosine phosphatase kappa (Ptprk) that led
      to complete loss of the transcript. The rat Ptprk gene exhibits 98% identity with
      the human and mouse counterparts and is expressed most abundantly in the CD4(
      )CD8(-) double-negative stage. The downregulation of Ptprk in mouse immature
      thymocytes by RNA interference mimicked the thid phenotype. These results
      indicate that thid maps to the Ptprk locus and that functional Ptprk is crucial
      for lineage commitment or progression of CD4(+) T cells. We also found that Ptprk
      appears to function in parallel with or downstream of Th-POK/cKrox (also known as
      ZBTB7B), a master regulator of T cell lineage decision.

PMID- 17434289
TI  - Comprehensive analysis of APOE and selected proximate markers for late-onset
      Alzheimer's disease: patterns of linkage disequilibrium and disease/marker
      association.
AB  - The epsilon(4) allele of APOE confers a two- to fourfold increased risk for late
      onset Alzheimer's disease (LOAD), but LOAD pathology does not all fit neatly
      around APOE. It is conceivable that genetic variation proximate to APOE
      contributes to LOAD risk. Therefore, we investigated the degree of linkage
      disequilibrium (LD) for a comprehensive set of 50 SNPs in and surrounding APOE
      using a substantial Caucasian sample of 1100 chromosomes. SNPs in APOE were
      further molecularly haplotyped to determine their phases. One set of SNPs in
      TOMM40, roughly 15 kb upstream of APOE, showed intriguing LD with the epsilon(4)
      allele and was strongly associated with the risk for developing LOAD. However,
      when all the SNPs were entered into a logit model, only the effect of APOE
      epsilon(4) remained significant. These observations diminish the possibility that
      loci in the TOMM40 gene may have a major effect on the risk for LOAD in
      Caucasians.

PMID- 17434292
TI  - Language lateralization in monozygotic twins discordant and concordant for
      schizophrenia. A functional MRI pilot study.
AB  - AIM: Previous studies have suggested altered structural and functional asymmetry
      of the brain in schizophrenia. METHODS: Functional MRI was used to assess
      differences in cortical activation during a verbal task in Broca's area and its
      contralateral homologue in four pairs of right-handed monozygotic (MZ) twins
      discordant and concordant for schizophrenia with low and high familial loading
      for the illness and four healthy control MZ twin pairs. RESULTS: Pooled data from
      all subjects with schizophrenia showed increased activation in the right
      homologue of Broca's area in contrast to healthy individuals. Concordant twins
      (i.e. high familial loading group) showed prominent between co-twin differences
      in lateralization index within given region of interest. Intra-pair differences
      in lateralization index were significantly higher in concordant twins compared to
      the controls (0.69+/-0.4 vs. 0.13+/-0.13, P<0.03), albeit no significant
      differences in the variable were shown between the discordant and control groups.
      CONCLUSION: This study provides evidence of reduced cerebral dominance for
      language processing in patients with schizophrenia. The findings further suggest
      the need for additional research on relative proportion of genetic and
      environmental factors underlying deviations of functional asymmetry in
      schizophrenia.

PMID- 17434291
TI  - Regulation of extracellular calcium in the hippocampus in vivo during
      epileptiform activity--role of astrocytes.
AB  - Astrocytes have been suggested to regulate the extracellular calcium
      concentration ([Ca(2+)](o)), but this has not been thoroughly investigated.
      Adult, male Sprague-Dawley rats were used to record changes in [Ca(2+)](o) in the
      hippocampus during epileptiform activity. Maximal decreases in [Ca(2+)](o) in CA1
      were measured in the pyramidal cell layer during 20 Hz, 20s stimulus trains to
      the contralateral CA3 region. Maximal decreases in [Ca(2+)](o) in the dentate
      gyrus were measured when maximal dentate activation had appeared-irrespective of
      the location, frequency or duration of the stimulation. Maximal decreases were
      36% greater in the dentate gyrus than in CA1. During prolonged discharges,
      [Ca(2+)](o) recovered partially towards the baseline in both hippocampal regions.
      To investigate the role of astrocytes, local injections of fluorocitrate (FC), a
      metabolic toxin selectively taken up by astrocytes, were used. FC (0.1, 0.25 or
      0.5mM FC), but not vehicle (2 microl), caused a small, but significant decrease
      in the maximal changes in CA1, but an increase in the dentate gyrus. The results
      suggest that maximal decreases in [Ca(2+)](o) occur in the hippocampus in
      response to burst firing of neurons and that astrocytes play a minimal role in
      the regulation of [Ca(2+)](o) during epileptiform activity.

PMID- 17434293
TI  - Caregiver psychoeducation for schizophrenia: is gender important?
AB  - INTRODUCTION: Females care for individuals with chronic illness more commonly
      than males and have different attitudes to illness. Additionally, they experience
      greater burden and reduced quality of life, when compared to their male
      counterparts. Since knowledge has been shown to be related to burden, we sought
      to determine whether there were gender differences in knowledge acquisition
      during a six-week caregiver psychoeducation programme (CPP). METHODS: Caregivers
      of people with schizophrenia completed a 23-item adapted version of the self
      report Family Questionnaire (FQ) before and after the six-week CPP. Using a
      Generalized Linear Mixed Model, we studied the differences in proportions of
      correct answers before and after the programme by gender. RESULTS: Over a 46
      month study period, 115 caregivers (58% female) participated in the programme.
      There was an overall improvement in knowledge with an effect size of 1.12. The
      improvement was statistically significant (P<0.001) within each of six specific
      areas of knowledge. However, female caregivers gained more knowledge overall and
      specifically regarding signs and symptoms, recovery and especially caregiver
      support. Knowledge gains regarding medication were roughly equal, while male
      caregivers gained more knowledge about risk factors. DISCUSSION: Our findings
      indicate that there are gender differences in the amount and type of knowledge
      gained during a CPP, with female caregivers showing greater knowledge acquisition
      than their male counterparts in most areas. Interventions designed to assist
      caregivers may be improved by targeting areas of knowledge specific to each
      gender. Such an approach might further reduce burden and improve the outcome for
      their relatives affected by schizophrenia.

PMID- 17434294
TI  - TRP channels in endothelial function and dysfunction.
AB  - Endothelial cells produce various factors that regulate vascular tone, vascular
      permeability, angiogenesis, and inflammatory responses. The dysfunction of
      endothelial cells is believed to be the major culprit in various cardiovascular
      diseases, including hypertension, atherosclerosis, heart and renal failure,
      coronary syndrome, thrombosis, and diabetes. Endothelial cells express multiple
      transient receptor potential (TRP) channel isoforms, the activity of which serves
      to modulate cytosolic Ca(2+) levels ([Ca(2+)](i)) and regulate membrane
      potential, both of which affect various physiological processes. The malfunction
      and dysregulation of TRP channels is associated with endothelial dysfunction,
      which is reflected by decreased nitric oxide (NO) bioavailability, inappropriate
      regulation of vascular smooth muscle tonicity, endothelial barrier dysfunction,
      increased oxidative damage, impaired anti-thrombogenic properties, and perturbed
      angiogenic competence. Evidence suggests that dysregulation of TRPC4 and -C1
      results in vascular endothelial barrier dysfunction; malfunction of TRPP1 and -P2
      impairs endothelial NO synthase; the reduced expression or activity of TRPC4 and 
      V1 impairs agonist-induced vascular relaxation; the decreased activity of TRPV4
      reduces flow-induced vascular responses; and the activity of TRPC3 and -C4 is
      associated with oxidative stress-induced endothelial damage. In this review, we
      present a comprehensive summary of the literature on the role of TRP channels in
      endothelial cells, with an emphasis on endothelial dysfunction.

PMID- 17434295
TI  - A new crown ether as vesicular carrier for 5-fluoruracil: synthesis,
      characterization and drug delivery evaluation.
AB  - Niosomes have shown promise as cheap and chemically stable drug delivery systems.
      In this paper a novel crown ether amphiphile, 1,16-hexadecanoyl-bis-(2
      aminomethyl)-18-crown-6 (Bola A-16), has been synthesized with the aim of
      developing a long time stable controlled release system. Niosomes have been
      prepared with different molar ratios of amphiphile and cholesterol and their
      morphological properties have been determined by quasi-elastic light scattering
      and transmission electron microscopy. The composition of niosomes affects the
      entrapment efficiency and the release rate of 5-fluorouracil, a well-known
      antineoplastic molecule. In addition, other two known azacrown ether amphiphiles
      (4,7,10,13-pentaoxa-16-aza-cyclooctadecane)-hexadecanedioc acid diamide (Bola D
      16) and alpha,omega-(4,7,10,13-pentaoxa-16-aza-cyclooctadecane)-hexadecane (Bola
      C-16), have been synthesized and the obtained vesicles have been characterized
      for comparison. Furthermore, the release profile of 5-fluorouracil in vitro, from
      these niosomes, has been studied over a period of 6h in order to simulate a
      hematic adsorption.

PMID- 17434296
TI  - Determination of carbaryl pesticide using amperometric acetylcholinesterase
      sensor formed by electrochemically deposited chitosan.
AB  - A sensitive, fast and cheap sensor for quantitative determination of carbaryl
      pesticide using amperometric acetylcholinesterase (AChE) sensor based on
      electrochemically deposited chitosan was reported. From a mildly acidic chitosan
      solution, a chitosan film is electrochemically deposited on Au electrode surface
      via a negative voltage bias, leading to a stable AChE sensor. The characteristics
      of the deposited layer were observed to be dependent upon the deposition time,
      pH, and the chitosan concentration. Fourier-transform infrared spectra proved
      that the immobilized enzyme could preserve their native structure due to the
      excellent biocompatibility and non-toxicity of chitosan. Under the optimal
      experimental conditions, the carbaryl inhibition on AChE-CHIT/Au was proportional
      to its concentration in two ranges, from 0.005 to 0.1 microg/ml and 0.5 to 5
      microg/ml, with the correlation coefficients of 0.9966 and 0.9982, respectively.
      The detection limit was 0.003 microg/ml taken as the concentration equivalent to
      a 10% decrease in signal. The determination of carbaryl in garlic samples
      obtained from export of farm base showed acceptable accuracy. The developed
      sensor exhibited good fabrication reproducibility and acceptable stability, which
      provided a new promising tool for pesticide analysis.

PMID- 17434297
TI  - Aerobic and anaerobic growth modes and expression of type 1 fimbriae in
      Salmonella.
AB  - The aim of this study was to clarify the growth rates of facultatively anaerobic
      Salmonella enterica serovar Enteritidis strain in aerobic and anaerobic
      conditions and the expression of type 1 fimbriae in relation to the growth
      phases. The cultivation was carried out in a Portable Microbe Enrichment Unit
      (PMEU) where in same conditions one can grow the cells in parallel by modifying,
      e.g. aerobiosis only. The results obtained show that although the anaerobic
      metabolism is generally believed to be a slower producer of biomass or
      metabolites, in these circumstances S. enterica serovar Enteritidis strain gave
      comparable growth rates in anaerobiosis with nitrogenation as in aerobic cultures
      with constant aeration. Fimbrial antigens were produced in the beginning of
      logarithmic phase of the growth cycle both in the aerobic and anaerobic
      conditions. The fimbria remained in the presence of oxygen. This capability is
      possibly used for the intrusion of oxygen containing tissues of host body by the
      invading pathogens. In conclusion S. enterica serovar Enteritidis strain
      suspensions grow equally well in constant nitrogenation and aeration, and fimbria
      were produced in both conditions, during the early logarithmic phase but they
      prevailed in the presence of aeration.

PMID- 17434298
TI  - [Genetic and molecular bases of neurocristopathies].

PMID- 17434299
TI  - Chemotherapy or no chemotherapy in clear margins after neoadjuvant chemoradiation
      in locally advanced rectal cancer: CHRONICLE. A randomised phase III trial of
      control vs. capecitabine plus oxaliplatin.

PMID- 17434300
TI  - Wing morphology and flight development in the short-nosed fruit bat Cynopterus
      sphinx.
AB  - Postnatal changes in wing morphology, flight development and aerodynamics were
      studied in captive free-flying short-nosed fruit bats, Cynopterus sphinx. Pups
      were reluctant to move until 25 days of age and started fluttering at the mean
      age of 40 days. The wingspan and wing area increased linearly until 45 days of
      age by which time the young bats exhibited clumsy flight with gentle turns. At
      birth, C. sphinx had less-developed handwings compared to armwings; however, the
      handwing developed faster than the armwing during the postnatal period. Young
      bats achieved sustained flight at 55 days of age. Wing loading decreased linearly
      until 35 days of age and thereafter increased to a maximum of 12.82 Nm(-2) at 125
      days of age. The logistic equation fitted the postnatal changes in wingspan and
      wing area better than the Gompertz and von Bertalanffy equations. The predicted
      minimum power speed (V(mp)) and maximum range speed (V(mr)) decreased until the
      onset of flight and thereafter the V(mp) and V(mr) increased linearly and
      approached 96.2% and 96.4%, respectively, of the speed of postpartum females at
      the age of 125 days. The requirement of minimum flight power (P(mp)) and maximum
      range power (P(mr)) increased until 85 days of age and thereafter stabilised. The
      minimum theoretical radius of banked turn (r(min)) decreased until 35 days of age
      and thereafter increased linearly and attained 86.5% of the r(min) of postpartum
      females at the age of 125 days.

PMID- 17434301
TI  - Chemical standardization of the aqueous extract of Cecropia glaziovii Sneth
      endowed with antihypertensive, bronchodilator, antiacid secretion and
      antidepressant-like activities.
AB  - This study reports the extraction process and standardization of the aqueous
      extract (AE) of a Cecropia species aiming its pharmacological characterization as
      a phytomedicine to be used in primary health care. The plant was originally
      collected in its environment, and was thereafter specially cultivated for the
      present work. To standardize the plant AE, several 2.0% tea of the dried leaves
      were prepared under controlled conditions and freeze dried. The AE (20% yield)
      was partitioned with n-butanol yielding the butanolic fraction (BuF; 1% yield).
      The activity of AE on vital organ functions (cardiovascular, respiratory,
      gastrointestinal and central nervous system) was determined in vivo. The effects
      of AE were compared to those of BuF in the same models and the relative potency
      determined. BuF was further evaluated in representative in vitro models to assess
      possible mechanisms of action. Chemical constituents of BuF were isolated in
      preparative HPLC columns yielding 10 highly purified compounds chemically
      identified as catechins (2), procyanidins (4), flavonoids (2), mixed sugars (1)
      and chlorogenic acid. All the compounds were identified by chemical analytic
      instrumentation (13C-NMR, 1H-NMR, LC-MS). Their relative concentrations in AE
      were ca 12% catechins, 19% procyanidins and 19% flavonoids. The pharmacological
      activity of the standardized AE is reported in accompanying papers.

PMID- 17434302
TI  - Oncological causes of frailty in older cancer patients.

PMID- 17434303
TI  - Synthesis and biological activity of naphthalene analogues of phenstatins:
      naphthylphenstatins.
AB  - Novel phenstatin analogues with a 2-naphthyl moiety combined with either a 2,3,4-
      or a 3,4,5-trimethoxyphenyl ring have been synthesized, and their tubulin
      polymerization inhibiting and cytotoxic activities have been evaluated. The 2
      naphthyl ring is a better replacement for the 3-hydroxy-4-methoxyphenyl ring in
      the phenstatin series than in the combretastatin series. For the
      naphthylphenstatins, the carbonyl is required, and the preferred orientation of
      the trimethoxyphenyl ring is the one found in combretastatins.

PMID- 17434304
TI  - 2-Aryl-2-hydroxyethylamine substituted 4-oxo-4,7-dihydrothieno[2,3-b]pyridines as
      broad-spectrum inhibitors of human herpesvirus polymerases.
AB  - A novel series of 2-aryl-2-hydroxyethylamine substituted 4-oxo-4,7
      dihydrothieno[2,3-b]pyridine-5-carboxamides have been identified as potent
      antivirals against human herpesviruses. These compounds demonstrate broad
      spectrum inhibition of the herpesvirus polymerases HCMV, HSV-1, EBV, and VZV with
      high specificity compared to human DNA polymerases.

PMID- 17434305
TI  - Hereditary myosin myopathies.
AB  - Hereditary myosin myopathies have emerged as a new group of muscle diseases with
      highly variable clinical features and onset during fetal development, childhood
      or adulthood. They are caused by mutations in skeletal muscle myosin heavy chain
      (MyHC) genes. Mutations have been reported in two of the three MyHC isoforms
      expressed in adult limb skeletal muscle: type I (slow/beta-cardiac MyHC; MYH7)
      and type IIa (MYH2). The majority of more than 200 dominant missense mutations in
      MYH7 are associated with hypertrophic/dilated cardiomyopathy without signs or
      symptoms of skeletal myopathy. Several mutations in two different parts of the
      slow/beta-cardiac MyHC rod region are associated with two distinct skeletal
      myopathies without cardiomyopathy: Laing early onset distal myopathy and myosin
      storage myopathy (MSM). However, early onset distal myopathy and MSM caused by
      MYH7 mutations may also occur together with cardiomyopathy. MSM affects proximal
      or scapuloperoneal muscles whereas Laing distal myopathy primarily affects the
      dorsiflexor muscles of the toes and ankles. MSM is morphologically characterized
      by subsarcolemmal accumulation of myosin in type 1 fibers, whereas Laing distal
      myopathy is associated with variable and unspecific muscle pathology, frequently
      with hypotrophic type 1 muscle fibers. A myopathy associated with a specific
      mutation in MYH2 is associated with congenital joint contractures and external
      ophthalmoplegia. The disease is mild in childhood but may be progressive in
      adulthood, with proximal muscle weakness affecting ambulation. Mutations in
      embryonic MyHC (MYH3) and perinatal MyHC (MYH8), which are myosin isoforms
      expressed during muscle development, are associated with distal arthrogryposis
      syndromes with no or minor muscle weakness. Clinical findings, muscle morphology
      and molecular genetics in hereditary myosin myopathies are summarized in this
      review.

PMID- 17434306
TI  - Cap disease uncapped.

PMID- 17434307
TI  - Cap disease caused by heterozygous deletion of the beta-tropomyosin gene TPM2.
AB  - "Cap myopathy" or "cap disease" is a congenital myopathy characterised by cap
      like structures at the periphery of muscle fibres, consisting of disarranged thin
      filaments with enlarged Z discs. Here we report a deletion in the beta
      tropomyosin (TPM2) gene causing cap disease in a 36-year-old male patient with
      congenital muscle weakness, myopathic facies and respiratory insufficiency. The
      mutation identified in this patient is an in-frame deletion (c.415_417delGAG) of
      one codon in exon 4 of TPM2 removing a single glutamate residue (p.Glu139del)
      from the beta-tropomyosin protein. This is expected to disrupt the seven-amino
      acid repeat essential for making a coiled coil, and thus to impair tropomyosin
      actin interaction. Missense mutations in TPM2 have previously been found to cause
      rare cases of nemaline myopathy and distal arthrogryposis. This mutation is one
      not previously described and the first genetic cause identified for cap disease.

PMID- 17434308
TI  - The push and pull of the bacterial cytoskeleton.
AB  - A crucial function for eukaryotic cytoskeletal filaments is to organize the
      intracellular space: facilitate communication across the cell and enable the
      active transport of cellular components. It was assumed for many years that the
      small size of the bacterial cell eliminates the need for a cytoskeleton, because
      simple diffusion of proteins is rapid over micron-scale distances. However, in
      the last decade, cytoskeletal proteins have indeed been found to exist in
      bacteria where they have an important role in organizing the bacterial cell.
      Here, we review the progress that has been made towards understanding the
      mechanisms by which bacterial cytoskeletal proteins influence cellular
      organization. These discoveries have advanced our understanding of bacterial
      physiology and provided insight into the evolution of the eukaryotic
      cytoskeleton.

PMID- 17434309
TI  - The implementation of a guideline of care for patients with a Sengstaken
      Blakemore tube in situ in a general intensive care unit using transitional change
      theory.
AB  - The use of the Sengstaken-Blakemore tube as a life-saving treatment for bleeding
      oesophageal varices is slowly becoming the least preferred method possibly due to
      the potential complications associated with its placement. Nursing practice
      pertaining to the care of this patient group appears ad hoc and reliant on local
      knowledge and experience as opposed to recognised evidence of best practice.
      Therefore, this paper focuses on the application of Lewin's transitional change
      theory used to introduce a change in nursing practice with the application of a
      guideline to enhance the care of patients with a Sengstaken-Blakemore tube in
      situ within a general intensive care unit. This method identified some of the
      complexities surrounding the change process including the driving and restraining
      forces that must be harnessed and minimised in order for the adoption of change
      to be successful.

PMID- 17434310
TI  - Dysphagia in acute ischaemic stroke: severity, recovery and relationship to
      stroke subtype.
AB  - Dysphagia in stroke is linked with increased risk of pneumonia, increased length
      of stay and poorer outcomes. This study followed a cohort of 88 acute ischaemic
      stroke patients admitted to hospitals in Perth, Western Australia, over 30 days.
      There were 8/88 deaths (9%). Infections were treated in 25/80 survivors (31%).
      Presence and severity of dysphagia were measured at 2 and 7 days post-stroke.
      Respiratory tract infections occurred at significantly higher rates for
      dysphagics (p<0.05). At 2 days post-stroke, the odds ratio (OR) of chest
      infection for dysphagics was 1.45 (95% CI=1.07-1.98). Survivors who were "nil by
      mouth" 2 days post-stroke were significantly more likely to develop pneumonia
      (p=0.01). At 7 days post-stroke, dysphagics were again more likely to develop
      pneumonia (p=0.014) with OR=1.77 (95% CI=1.26-2.49). The total anterior
      circulation infarcts demonstrated more severe and prolonged dysphagia than other
      stroke subtypes.

PMID- 17434311
TI  - Dissecting ICRAC, a store-operated calcium current.
AB  - The use of Ca(2+) for intracellular signalling necessitates tight local and
      global control of cytoplasmic Ca(2+) concentration, and mechanisms for
      maintaining the net Ca(2+) balance. It has long been recognized that
      intracellular Ca(2+) stores exert control over Ca(2+) influx at the plasma
      membrane through a process of store-operated Ca(2+) entry (SOCE). The Ca(2+)
      current I(CRAC) is the best characterized instance of SOCE, but the elements of
      the pathway leading to I(CRAC) have eluded biochemical definition for more than a
      decade. However, the recent identification of key proteins underlying I(CRAC)-
      STIM1 and Orai1--has led to several insights into this ER-to-plasma membrane
      signalling system and to the recognition that it is an ancient and conserved
      mechanism in multicellular organisms.

PMID- 17434312
TI  - Synthesis of pH-sensitive amphotericin B-poly(ethylene glycol) conjugates and
      study of their controlled release in vitro.
AB  - New intravenous conjugates of amphotericin B (AMB) with poly(ethylene glycols)
      (PEG) (M=5000, 10,000, 20,000) have been synthesized and characterised. The
      intermediate PEGs possess a 1,4-disubstituted benzene ring with aldehyde group at
      the end of the chain. The benzene ring is connected with PEG at its 4-position
      (with respect to the aldehyde group) by various functional groups (ether, amide,
      ester). Reaction of terminal aldehyde group of the substituted PEGs with AMB gave
      conjugates containing a pH-sensitive imine linkage, which can be presumed to
      exhibit antimycotic effect at sites with lowered pH value. All types of the
      conjugates are relatively stable in phosphate buffer at physiological conditions
      of pH 7.4 (37 degrees C), less than 5 mol% AMB being split off from them within
      24 h. For a model medium of afflicted tissue was used a phosphate buffer (pH 5.5,
      37 degrees C), in which controlled release of AMB from the conjugates takes
      place. The imine linkage is split to give free AMB with half-lives of 2-45 min.
      The rate of acid catalysed hydrolysis depends upon substitution of the benzene
      ring; however, it does not depend on molecular weights of the PEGs used. The
      conjugates with ester linkage undergo enzymatic splitting in human blood plasma
      and/or blood serum at pH 7.4 (37 degrees C) with half-lives of 2-5 h depending on
      molecular weights of the PEGs used (M = 5000, 10,000, 20,000). At first, the
      splitting of ester linkage produces the relatively stable pro-drug, that is, 4
      carboxybenzylideniminoamphotericin B, which is decomposed to AMB and 4
      formylbenzoic acid in a goal-directed manner only at pH 7 (t1/2 = 2 min, pH 5.5,
      37 degrees C). A goal-directed release of AMB is only achieved by acid catalysed
      hydrolysis of imine linkage, either from the polymeric conjugate or from the pro
      drug released thereof. The LD50 values determined in vivo (mouse) are 20.7 mg/kg
      and 40.5 mg/kg for the conjugates with ester linkage (M = 10,000 and 5000,
      respectively), which means that they are ca. 6-11 times less toxic than free AMB.

PMID- 17434313
TI  - Validation of alternative methods of preparing 99mTc-MAG3.
AB  - Parameters in the preparation of 99mTc-mertiatide (99mTc-MAG3) were investigated
      to determine the importance of total activity, activity concentration, boiling
      time, and delay before boiling for the radiochemical purity (RCP) and stability
      of the product. Satisfactory RCP results (>90%) were obtained over a range of
      concentrations including a dilute preparation for paediatric use. RCP was not
      affected by the time between the addition of pertechnetate and boiling, but low
      RCP (<60%) resulted when the kit was boiled for less than 10 min.

PMID- 17434314
TI  - Expression patterns of MLC1 protein in the central and peripheral nervous
      systems.
AB  - Mutations in MLC1 cause megalencephalic leukoencephalopathy with subcortical
      cysts (MLC), a disorder characterized clinically by macrocephaly, deterioration
      of motor functions, epilepsy and mental decline. Recent studies have detected
      MLC1 mRNA and protein in astroglial processes. In addition, our group previously
      reported MLC1 expression in some neurons in the adult mouse brain. Here we
      performed an exhaustive study of the expression pattern of MLC1 in the developing
      mouse brain by means of optic and electron microscopy. In the central nervous
      system, MLC1 was detected mainly in axonal tracts early in development. In
      addition, MLC1 was also observed in the peripheral nervous system and in several
      sensory epithelia, as retina or saccula maculae. Post-embedding immunogold
      experiments indicated that MLC1 is localized in astrocyte-astrocyte junctions,
      but not in the perivascular membrane, indicating that MLC1 is not a component of
      the dystrophin-glycoprotein complex. In neurons, MLC1 is located at the plasma
      membrane and vesicular structures. Our data provide a mouse MLC1 expression map
      that could be useful to understand the phenotype of MLC patients, and suggested
      that MLC disease is caused by an astrocytic and a neuronal dysfunction.

PMID- 17434315
TI  - Methicillin resistant Staphylococcus aureus infections following cardiac surgery:
      incidence, impact and identifying adverse outcome traits.
AB  - OBJECTIVE: To assess the incidence and impact of Methicillin-resistant
      Staphylococcus aureus (MRSA) infections on cardiac surgery outcomes and to
      identify adverse outcome traits. METHODS: Retrospective analysis of prospectively
      collected data from cardiac surgical and microbiology databases between April
      2000 and March 2005. The overall and yearly incidence of positive MRSA cultures
      was examined along with the distribution of clinical infections and the
      associated mortality. Pre-operative patient characteristics were analysed between
      non-survivors and survivors of MRSA infections. Multivariate logistic regression
      was used to assess the relationship between pre-operative patient characteristics
      and in-hospital mortality in patients with MRSA. A comparison of post-operative
      outcomes between non-survivors and survivors of MRSA infections was also carried
      out and included in the logistic regression analysis. RESULTS: There were 319
      patients with positive MRSA cultures during the study period with an overall
      incidence of 3.9%. Yearly incidence ranged from 2.4% to 5.2%. There were 120
      carriers with pre-operative positive cultures of which 25 developed clinical
      surgical infections leaving 224 patients as the study group. Overall mortality in
      patients with MRSA during the study period was 12.9%(41/319). Mortality in the
      study group was 17.8% (40/224). Mortality comparison between MRSA and non-MRSA
      mediastinitis was 26.7%(8/30) and 17.1%(13/76), respectively (p=0.26). Mortality
      between MRSA and non-MRSA septicaemia was 46.9% (15/32) and 52.9% (37/70)
      (p=0.57). Applying the logistic EuroSCORE to the MRSA patients revealed that non
      survivors had a significantly higher pre-operative risk of 10.4% compared to
      survivors with a pre-operative risk of 6.2% (p=0.003). Renal dysfunction and poor
      ejection fraction were found to be pre-operative factors associated with
      mortality in MRSA patients following the multivariate logistic regression
      analysis. Non-survivors had longer stays on intensive care, longer ventilation
      times, and were more likely to require support with balloon pumps and
      haemofiltration. MRSA septicaemia and length of ventilation were significantly
      associated with mortality in MRSA patients ahead of pre-operative
      characteristics. CONCLUSIONS: The incidence of MRSA is low, but carries a high
      mortality. MRSA septicaemia and mediastinitis have the highest associated
      mortality; however, this is not significantly different from non-MRSA infections.
      Patients with MRSA who die have higher pre-operative risk and have a poorer post
      operative course than survivors.

PMID- 17434316
TI  - Dynamics of antigen-specific regulatory T-cells in the context of autoimmunity.
AB  - Naturally occurring regulatory T-cells (nT-reg) are crucial in preventing
      generalized autoimmunity. However, antigen-specific T-reg responses during organ
      specific autoimmunity have not been characterized until recently when novel tools
      including MHC class II-tetramers and Foxp3gfp "knock-in" reporter mice
      (Foxp3gfp.KI) became available. In this review, we introduce the concept of
      functional compartmentalisation in that T-reg may behave differently when they
      maintain peripheral tolerance in the secondary lymphoid tissue in a non
      inflammatory environment as compared to when they are expanded and targeted to
      the site of inflammation following an autoantigen-specific, immunogenic stimulus.

PMID- 17434317
TI  - Systematic analysis of fusion and affinity tags using human aspartyl-tRNA
      synthetase expressed in E. coli.
AB  - Fusion and affinity tags are popular tools for the expression of mammalian
      proteins in bacteria. To facilitate the selection of expression approaches, a
      systematic comparison was performed. We cloned, sequenced, and expressed in
      Escherichia coli ubiquitin- and SUMO-hDRS fusion proteins with biotin- or 6xHis
      tags. The tagging of hDRS with ubiquitin or SUMO was necessary to express
      properly folded and biologically active enzyme. Similar enhancement of hDRS
      activity was obtained by fusion to ubiquitin or SUMO. Ubiquitin, SUMO, biotin,
      and hexahistidine tags did not appreciably interfere with hDRS activity. Fusion
      proteins were specifically cleaved without altering the N-terminal of hDRS. After
      cleavage hDRS remained soluble and active with a specific activity comparable to
      that of the fused protein. Similar activity was observed with biotin- and 6xHis
      tagging of hDRS. Higher purity but significantly lower yields of hDRS were
      obtained using biotin-tagging. Overall we demonstrated ubiquitin and SUMO fusion
      proteins similarly enhanced the proper folding of hDRS expressed in E. coli. In
      comparison to previous expressions of hDRS as a GST fusion, ubiquitin, and SUMO
      fusions provided higher yields and easier purification and cleavage.

PMID- 17434318
TI  - Human topoisomerase I C-terminal domain fragment containing the active site
      tyrosine is a molten globule: implication for the formation of competent
      productive complex.
AB  - Human topoisomerase I (topo I) is an essential cellular enzyme that relaxes DNA
      supercoiling. The 6.3 kDa C-terminal domain of topo I contains the active site
      tyrosine (Tyr723) but lacks enzymatic activity by itself. Activity can be fully
      reconstituted when the C-terminal domain is associated with the 56 kDa core
      domain. Even though several crystal structures of topo I/DNA complexes are
      available, crystal structures of the free topo I protein or its individual domain
      fragments have been difficult to obtain. In this report we analyze the human topo
      I C-terminal domain structure using a variety of biophysical methods. Our results
      indicate that this fragment protein (topo6.3) appears to be in a molten globule
      state. It appears to have a native-like tertiary fold that contains a large
      population of alpha-helix secondary structure and extensive surface hydrophobic
      regions. Topo6.3 is known to be readily activated with the association of the
      topo I core domain, and the molten globule state of topo6.3 is likely to be an
      energy-favorable conformation for the free topo I C-terminal domain protein. The
      structural fluctuation and plasticity may represent an efficient mechanism in the
      topo I functional pathway, where the flexibility aids in the complementary
      association with the core domain and in the formation of a fully productive topo
      I complex.

PMID- 17434319
TI  - Effect of dietary supplementation of probiotic and vitamin C on the immune
      response of Indian major carp, Labeo rohita (Ham.).
AB  - The immunostimulatory effect of probiotics and vitamin C has been established in
      many systems including fish. An investigation was carried out to study the effect
      of dietary supplementation of a probiotic bacterium "Bacillus subtilis", vitamin
      C in the form of ascorbyl polyphosphate and their combination on the immune
      response of Indian major carp, rohu, (Labeo rohita Ham.) fingerlings fed for a
      period of 60 days. The total serum protein and globulin content was significantly
      higher (p<0.05) in probiotic (B. subtilis @ 10(8) CFU/g of the feed) fed group
      while the respiratory burst activity of blood neutrophils was significantly high
      in vitamin C (ascorbyl polyphosphate @100 mg per kg diet) fed group. The antibody
      level was significantly high in Bacillus subtilis treated group followed by the
      probiotic (B. subtilis @ 10(8) CFU/g of the feed) and ascorbyl polyphosphate
      (ascorbyl polyphosphate @100 mg per kg diet) combined group. The least percentage
      of mortality was recorded in B. subtilis treated group (25%) followed by 35 and
      40% in ascorbyl polyphosphate treated and B. subtilis and ascorbyl polyphosphate
      combined groups, respectively.

PMID- 17434320
TI  - Cytokine expression in the intestine of rainbow trout (Oncorhynchus mykiss)
      during infection with Aeromonas salmonicida.
AB  - Gene expression of a number of cytokines in the intestine of rainbow trout
      (Oncorhynchus mykiss) was investigated after challenge with a pathogenic strain
      of Aeromonas salmonicida. Fish were exposed to A. salmonicida by immersion in a
      bacterial suspension (bath challenge) and tissue samples of the distal and
      proximal intestine were collected at days 0, 2, 4, 6 and 8 post-exposure. Head
      kidney tissue was also collected to assess the effect in a systemic immune
      tissue. A classic profile of pro-inflammatory cytokine upregulation was observed
      in the proximal intestine of fish infected by bath challenge, as determined by
      semi-quantitative RT-PCR. Expression of IL-1beta, IL-8, TNF-alpha and IFN-gamma
      was increased in the proximal intestine. TGF-beta was significantly decreased in
      the distal intestine. In the head kidney, infection with A. salmonicida by bath
      challenge caused decreased expression levels of IL-1beta, IL-8, TNF-alpha and TGF
      beta. The results are discussed in the context of potential immune mechanisms in
      the gut to prevent infection.

PMID- 17434321
TI  - Comparative analysis of motor unit action potentials of the medial gastrocnemius
      muscle in cats and rats.
AB  - Properties of motor unit action potentials (MUAPs) were compared for medial
      gastrocnemius (MG) motor units (MUs) in cats and rats. The experiments on
      functionally isolated MUs were performed under general anaesthesia, under
      comparable conditions (surgery, stimulating protocol and recording methods) for
      both species investigated. The proportions of motor units and contractile
      properties of the sample used in the study were consistent with previous studies
      performed on the MG muscle in both animal species, so comparisons of action
      potentials of individual types of MUs were acknowledged as fully reliable. The
      most prominent differences concerning MUAPs were observed in total duration and
      peak-to-peak times which for all MU types were about twice longer in cat MUs, in
      comparison to the rat MUs. The considerable disproportions were observed between
      the MUAP amplitudes of FF (fast fatigable), FR (fast resistant to fatigue) and S
      (slow) MUs in each species (the highest amplitudes were measured for FF and the
      lowest for S MUs), but there were no significant differences between cat and rat
      when respective types of MUs were compared. The shapes of MUAPs were commonly
      characterized by biphasic waveforms composed of two or three turns in all types
      of units, and no interspecies differences were revealed. Several factors
      influencing MUAP parameters were discussed indicating most of all importance of
      variable length of cat and rat muscle fibres and ambiguous influence of motor
      unit size, thickness of muscle fibres and their density around the recording
      electrode in the MG muscle of both species.

PMID- 17434322
TI  - Does manual mobilization influence motion coupling patterns in the atlanto-axial
      joint?
AB  - BACKGROUND: A restricted number of publications have reported on the analysis of
      coupling patterns in the atlanto-axial joint using an in vitro set-up applying
      pure moments of forces. The aim of this study is to analyze segmental motion
      coupling patterns during cervical manual mobilization. METHODS: The position and
      attitudes of sensors mounted on the atlas and axis were traced in nine embalmed
      and one fresh human spinal specimen using an electromagnetic tracking system.
      Segmental bony reference points were registered using a 3D-digitizing stylus for
      the definition of bone embedded coordinate systems. Segmental motion coupling was
      recorded for the atlanto-axial joints during manual mobilization through the full
      range of axial rotation and lateral bending. RESULTS: Coupled motions were
      described by the direction of the associated motion and by cross-correlation
      analysis. The results confirm the contra-lateral coupling pattern of axial
      rotation with lateral bending at C1-C2 observed in previous studies. The cross
      correlation analysis offered a more objective interpretation of the coupling
      pattern for the analysis of the more irregular coupling patterns during lateral
      bending. Inter-individual differences in coupling patterns were observed.
      INTERPRETATIONS: The presented method provides possibilities for the study of
      coupled motion during manual diagnostic and therapeutic practice. Practitioners
      should be aware of the segmental 3D-aspects of manually induced so called planar
      mobilizations and their possible influence on motion coupling. Motion coupling
      patterns may be related to specimen specific anatomy.

PMID- 17434323
TI  - Felt presence: paranoid delusion or hallucinatory social imagery?
AB  - Cheyne and Girard characterize felt presence (FP) during sleep paralysis attacks
      as a pre-hallucinatory expression of a threat-activated vigilance system. While
      their results may be consistent with this interpretation, they are nonetheless
      correlational and do not address a parsimonious alternative explanation. This
      alternative stipulates that FP is a purely spatial, hallucinatory form of a
      common cognitive phenomenon-social imagery-that is often, but not necessarily,
      linked with threat and fear and that may induce distress among susceptible
      individuals. The occurrence of both fearful and non-fearful FPs in a multiplicity
      of situations other than sleep paralysis attacks supports the notion that FPs are
      hallucinatory variants of social imagery and that they are not necessarily bound
      to threat-activated vigilance. Evidence linking FPs with anxiety disorders
      supports the notion that the distress they evoke may be mediated by a more
      general affective distress personality factor. To illustrate the predominantly
      spatial character of FP hallucinations, similarities between FP and phantom limbs
      are summarized and the possibility that these two phenomena are parallel
      expressions (self- vs. other-presence) of a mirror neuron system is considered.

PMID- 17434324
TI  - Changes in the spleen and liver of pregnant sows and full-term piglets after
      feeding diets naturally contaminated with deoxynivalenol and zearalenone.
AB  - Wheat contaminated naturally with the Fusarium toxins deoxynivalenol (DON) and
      zearalenone (ZON) was fed to pregnant Landrace sows for 35days. On day 110,
      caesarean section was carried out, the offspring were killed immediately after
      birth, and their livers and spleens examined. At necropsy there were no
      macroscopic lesions observed in any organ of either sows or piglets.
      Histopathological evaluation of tissues from sows of the treated group revealed
      changes in liver and spleen tissues, whereas no significant changes were observed
      in these tissues in their piglets. Liver damage, as measured by prominent
      elevated transaminase activities, was not detected in the serum of the sows. In
      pregnant sows there were individual variations in sensitivity to the Fusarium
      toxins. In conclusion, it can be assumed that there are no adverse effects on the
      liver and spleen of full-term piglets when their mothers consumed diets
      containing up to 9570 and 358mug DON/ZON per kg diet.

PMID- 17434325
TI  - Histological and serological evidence of disease among invasive, non-native
      stoats Mustela erminea.
AB  - Invasive, non-native species are a major threat to global biodiversity. Stoats
      were introduced from Britain to New Zealand in the 1880s and have since caused
      grave conservation problems. A histopathological and serological survey of
      disease and infection in stoats from New Zealand was undertaken to identify
      agents that might be used or modified to control this population. Of 60 stoats
      examined, 63% exhibited inflammation of the lung, mostly occurring as local or
      diffuse interstitial pneumonia, 30% showed signs of inflammatory liver disease
      and 14% were positive for antibodies reactive with feline calicivirus. In Britain
      only 11% of 44 stoats exhibited symptoms of pulmonary inflammatory disease,
      suggesting higher rates of infection or compromise of the pulmonary immune system
      among invasive stoats, possibly related to genetic founder effects or
      environmental variation. These findings could be exploited in biological control
      programmes.

PMID- 17434326
TI  - A bibliometric analysis of the Journal of Molecular Graphics and Modelling.
AB  - This paper reviews the articles published in Volumes 2-24 of the Journal of
      Molecular Graphics and Modelling (formerly the Journal of Molecular Graphics),
      focusing on the changes that have occurred in the subject over the years, and on
      the most productive and most cited authors and institutions. The most cited
      papers are those describing systems or algorithms, but the proportion of these
      types of article is decreasing as more applications of molecular graphics and
      molecular modelling are reported.

PMID- 17434327
TI  - Pretreatment with olprinone hydrochloride, a phosphodiesterase III inhibitor,
      attenuates lipopolysaccharide-induced lung injury via an anti-inflammatory
      effect.
AB  - PURPOSE: Acute respiratory distress syndrome is characterized by neutrophil
      accumulation in the lungs and the activation of several cytokines produced by
      macrophages. Olprinone hydrochloride, a specific phosphodiesterase III inhibitor,
      has anti-inflammatory effects and inhibits the activation of macrophages, in
      addition to its inotropic and vasodilatory effects. The purpose of this study was
      to examine the beneficial effects of olprinone on lipopolysaccharide (LPS)
      induced pulmonary inflammation. MATERIALS AND METHODS: Lung inflammation was
      produced by intravenous LPS injection into rats. The rats were divided into four
      groups: a vehicle group in which normal saline was injected, an olprinone group
      in which olprinone was injected at a dose of 0.2mg/kg, a dexamethasone group in
      which dexamethasone was injected at a dose of 5mg/kg, and a control group. In
      each group, drug was injected intraperitoneally 30 min before the intravenous
      administration of LPS. The blood was obtained at 1h and then animals were
      sacrificed at 6h and blood and lung specimen were obtained for cytokine analysis
      and pathological examination. On another set of experiment, bronchioloalveolar
      lavage (BAL) was performed for cytokine analysis of BAL fluid. The macrophages
      isolated from normal rat by BAL were cultured in vitro with the presence of LPS
      and olprinone or dexamethasone, and supernatant was collected. The levels of
      several cytokines in the serum, in the BAL fluid, and in the culture supernatant
      were determined. RESULTS: The animals injected with LPS were found to have an
      influx of neutrophils in the lungs, and inflammatory cytokines, such as TNF-alpha
      and IL-6, and anti-inflammatory cytokine IL-10 were produced. Pretreatment with
      olprinone or dexamethasone significantly inhibited the LPS-induced neutrophil
      influx into the lungs, suppressed inflammatory cytokines TNF-alpha and IL-6. The
      level of anti-inflammatory cytokine IL-10 increased in an olprinone group. The
      inhibition of TNF-alpha and IL-6, and the augmentation of IL-10 release were also
      observed in in vitro culture of isolated rat alveolar macrophages when olprinone
      (10(-5)mol/ml) and LPS (10 microg/ml) were cultured together. However, the level
      of IL-10 in serum and culture supernatant was suppressed in a dexamesathone
      group. CONCLUSION: LPS-induced lung inflammation is strongly inhibited by
      olprinone accompanying the enhancement of IL-10 and the inhibition of
      inflammatory cytokines. Results of the in vitro experiment suggest that alveolar
      macrophages may play an important role in ameliorating LPS-induced lung
      inflammation and the mechanism of its effect is different from that of steroid.

PMID- 17434328
TI  - Peptidoglycan recognition protein (PGRP) from eri-silkworm, Samia cynthia ricini;
      protein purification and induction of the gene expression.
AB  - Peptidoglycan recognition protein (PGRP) was isolated from immunized hemolymph of
      the wild silkworm, Samia cynthia ricini, detecting the biding activity with
      (125)I-labeled peptidoglycan (PGN). The binding specificity of PGRP was tested by
      competitive inhibition of the binding to (125)I-labeled-PGN by a large excess
      amount of non-labeled-PGN or other glucans. The binding to labeled uncross-linked
      Lys-type PGN from Micrococcus luteus was strongly inhibited by non-labeled-PGN of
      the same structure and meso-diaminopimelic acid (DAP)-type cross-linked PGN from
      Bacillus cell wall, but only a little by cross-linked PGN from M. luteus cell
      wall. The PGRP cDNA encodes a 193 amino acid open reading frame. The deduced
      amino acid sequence had 62 to 91% identities to known lepidopteran PGRPs, but
      less than 40% to Drosophila PGRPs. The PGRP gene constitutively expressed at a
      low level in naive fat body, and strongly induced by an injection of DAP-type
      cross-linked and Lys-type uncross-linked PGNs, but only weakly by Lys-type cross
      linked PGN from M. luteus. The silkworm possibly distinguish between PGNs based
      on the structure of cross-linking peptide, but has less if any preference for the
      diamino acid residue of the stem peptide.

PMID- 17434329
TI  - Rational approaches to developing an anti-disease vaccine against malaria.
AB  - Vaccination against pathogen toxins provides a rational approach to prevent
      morbidity and mortality, and is widely validated in the context of bacterial
      infections. A saccharide-conjugate vaccine targeting the malaria
      glycosylphosphatidylinositol toxin glycan could therefore prevent severe disease.
      This strategy could also reduce the risk posed by 'rebound' infections or
      immunopathology associated with other interventions.

PMID- 17434330
TI  - [Comparison of different biomaterials for vaginal surgery using an in vivo model
      of meshes infection in rats].
AB  - OBJECTIVES: The purpose of this study was to develop an animal model of
      prosthetic infection and compare in vivo bacterial infectiosity of different
      biomaterials used in vaginal surgery. MATERIALS AND METHODS: We implanted 36
      prostheses of poly(lactic acid) with 94% L forms (PLA94), in a model of
      incisional abdominal hernia in Wistar rats. Bacterial inoculation was done just
      after implantation with three strains of Escherichia coli of variable virulence,
      two different concentrations and two different times of inoculation (during
      surgery or 48 hours after). All meshes were explanted and animals sacrificed on
      day 30 after intervention. Bacteriology and histology were then performed. In the
      same way, three materials used in vaginal surgery (knitted light-weight
      polypropylene [PP], thermoformed PP [Uratape] and polyurethane coated
      poly[ethylene terephtalate] [PTFE]) were tested and compared to the PLA94 using
      the same protocol. RESULTS: All inoculated prostheses were still infected at day
      30 after implantation with the same E. coli strain. There was a significant
      difference in bacterial infectiosity linked to virulence of the inoculated strain
      (p=.005) and the amount injected (P<0.001). Infectiosity was significantly lower
      for PLA94 when compared to the three other prostheses (P=0.008). The most
      important infectiosity was seen with PTFE and thermoformed PP. For histologists,
      PLA94 also gave the weakest inflammatory reaction. DISCUSSION AND CONCLUSION: An
      original animal model of prosthetic infection allowed us to compare in vivo
      bacterial infectiosity of different biomaterials used in vaginal surgery and to
      demonstrate that the PLA94 mesh induces a milder risk of infection than
      polypropylene.

PMID- 17434331
TI  - [Paradoxical interactions between pregnancy and breast cancer].
AB  - Interactions between pregnancy and breast cancer are complex and paradoxical.
      Epidemiological data show that nulliparity and late full-term pregnancy increase
      breast cancer risk. By contrast, early full-term pregnancy and multiparity are
      thought to be the most effective means of decreasing lifetime breast cancer risk.
      Paradoxically, young women diagnosed with breast cancer during pregnancy have a
      higher risk of dying from their disease. Moreover, there is a transient increase
      in risk of breast cancer in the first three to four years after pregnancy. After
      breast cancer treatment, there is no evidence that pregnancy increases the risk
      of breast cancer recurrence. Thus, it is not contraindicated in women previously
      treated for breast cancer and free of recurrence. Various physio-pathological
      mechanisms are involved in the protective effect of pregnancy, like cellular
      differentiation of mammary cells, mammary gland involution, circulating anti
      mucin antibody and excretion in the milk of breast carcinogens. In the past,
      unfavorable effects of pregnancy were mainly attributed to precancerous cell
      proliferation induced by pregnancy-associated hormonal changes. However, recent
      studies suggest that the remodeling of cellular microenvironment and
      extracellular matrix during pregnancy and involution may contribute to enhanced
      invasive and metastatic potential of breast carcinomas.

PMID- 17434332
TI  - Passing the message on: inheritance of epigenetic traits.
AB  - Epigenetic modifiers play an important role in genome organization, stability and
      the control of gene expression. Three research groups that are exploring the
      transfer of epigenetic information between generations have recently published
      papers. Mary Alleman et al. have shown that RNA-directed chromatin changes
      mediate paramutation in maize, and Minoo Rassoulzadegan et al. have demonstrated
      that RNA also plays a role in paramutation in mice. A new aspect of epigenetic
      regulation has been revealed by Jean Molinier et al. - they have demonstrated
      that the memory of exposure to stress is transferred through several generations.

PMID- 17434333
TI  - Investigation on the thermal stability of PVC filled with hydrotalcite by the UV
      vis spectroscopy.
AB  - The thermal stability of the polyvinyl chloride (PVC) filled with hydrotalcite
      was studied in this paper. It was found that the stability of the PVC resin mixed
      with organic Sn and hydrotalcite was better than that of the PVC resin mixed with
      organic Sn alone. The UV-vis spectra showed that under certain heat treatment
      conditions, the sample without hydrotalcite embodied relatively high content of
      the conjugated double bonds with the chain length of about 3-5, however, the
      content of the conjugated double bond with the chain length of about 7 was
      greatly increased when the hydrotalcite was filled into the PVC resin. The
      hydrotalcite could inhibit the thermal degradation process of PVC resin in ionic
      mechanism.

PMID- 17434335
TI  - Photoelectron spectroscopy and substituent effects in halonaphthalenes.
AB  - The electronic structure of two isomeric dibromonaphthalenes (C(10)H(6)Br(2)) has
      been investigated by HeI/HeII photoelectron spectroscopy. The spectra were
      assigned by Green's functions calculations and comparison with the spectra of
      related dibromobenzenes (C(6)H(4)Br(2)). The analysis of pi-orbital and halogen
      lone pair ionization energies, enabled us to determine the magnitude of bromine
      bromine intramolecular interactions and distinguish between through-bond and
      through-space type interactions. We also discuss the halogen-halogen interactions
      in other polynuclear aromatics.

PMID- 17434334
TI  - A novel method for study of the aggregation of protein induced by metal ion
      aluminum(III) using resonance Rayleigh scattering technique.
AB  - We present a novel method for the study of the aggregation of protein induced by
      metal ion aluminum(III) using resonance Rayleigh scattering (RRS) technique. In
      neutral Tris-HCl medium, the effect of this aggregation of protein results in the
      enhancement of RRS intensity and the relationship between the enhancement of the
      RRS signal and the Al concentration is nonlinear. On this basis, we established a
      new method for the determination of the critical induced-aggregation
      concentrations (C(CIAC)) of metal ion Al(III) inducing the protein aggregation.
      Our results show that many factors, such as, pH value, anions, salts, temperature
      and solvents have obvious effects. We also studied the extent of aggregation and
      structural changes using ultra-violet spectrometry, protein intrinsic
      fluorescence and circular dichroism to further understand the exact mechanisms of
      the aggregation characteristics of proteins induced by metal ion Al(III) at the
      molecular level, to help us to develop effective methods to investigate the
      toxicity of metal ion Al, and to provide theoretical and quantitative evidences
      for the development of appropriate treatments for neurodementia such as
      Parkinson's disease, Alzheimer's disease and dementia related to dialysis.

PMID- 17434336
TI  - Photoluminescence and electroluminescence of methoxy and carboethoxy derivatives
      of 1,3-diphenyl-1H-pyrazolo[3,4-b]quinoline.
AB  - A series of methoxy (MO) and carboethoxy (CE) derivatives of 1,3-diphenyl-1H
      pyrazolo[3,4-b]quinoline ([DPPQ]) are characterized by spectroscopic methods. All
      dyes show the photoluminescent spectra which are highly solvatochromic. In the
      case of 6MO[DPPQ] and 6CE[DPPQ] the emission bands are broad and shifted to the
      red with increasing of solvent polarity whereas the dyes 6MO1pMO[DPPQ] and
      6MO13pMO[DPPQ] exhibit a reverse solvatochromism. The large difference between
      the excited- and state-dipole moments indicates a strong electron transfer
      effects in all dyes. The EL spectra are obtained for the fabricated OLEDs with a
      general structure of EL device ITO/PVK:6X[DPPQ]/Ca/Al. The blue emission
      originating from PVK host matrix appears to be quenched in EL spectra of doped
      PVK matrix giving rise to emission in blue, blue-green or green spectral regions.
      The obtained results demonstrate that a series of newly synthesized methoxy and
      carboethoxy [DPPQ]-derivatives may be considered as promising materials for
      electroluminescent applications.

PMID- 17434338
TI  - Applying emergent ubiquitous technologies in health: the need to respond to new
      challenges of opportunity, expectation, and responsibility.
AB  - In spite of their name, 'ubiquitous' technologies are not yet ubiquitous in the
      true sense of the word, but rather are 'novel', being at the research, pilot, and
      selective use stages. In future, the proliferation in types of application, the
      major increase in cases and data volumes, and above all the dependence on
      ubiquitous technologies to monitor persons at risk, will raise practical,
      ethical, and liability issues. Equally significantly, it will require health
      service redesign, including new response services. Health informaticians need to
      be active in stimulating consideration of all these issues, as part of both
      social and professional responsibility.

PMID- 17434337
TI  - An effort to improve electronic health record medication list accuracy between
      visits: patients' and physicians' response.
AB  - OBJECTIVE: To evaluate the efficacy of a secure web-based patient portal called
      Patient Gateway (PG) in producing more accurate medication lists in the
      electronic health record (EHR), and whether sending primary care physicians
      (PCPs) a clinical message updating them on the information their patients
      provided caused physicians to update the EHR medication list. METHODS: We
      compared the medication list accuracy of 84 patients using PG with that of 79 who
      were not. Patient-reported medication discrepancies were noted in the EHR in a
      clinical note by research staff and a message was sent to the participants' PCPs
      notifying them of the updated information. RESULTS: Participants were taking 665
      medications according to the EHR, and reported 273 additional medications. A
      lower percentage of PG users' drug regimens (54% versus 61%, p=0.07) were
      reported to be correct than those of PG non-users, although PG users took
      significantly more medications than their non-user counterparts (5.0 versus 3.1
      medications, p=0.0001). Providing patient-reported information in a clinical note
      and sending a clinical message to the primary care doctor did not result in PCPs
      updating their patients' EHR medication lists. CONCLUSIONS: Medication lists in
      EHRs were frequently inaccurate and most frequently overlooked over-the-counter
      (OTC) and non-prescription drugs. Patients using a secure portal had just as many
      discrepancies between medication lists and self-report as those who did not, and
      notifying physicians of discrepancies via e-mail had no effect.

PMID- 17434339
TI  - Hepatitis C virus (HCV) coinfection in a cohort of HIV positive long-term non
      progressors: possible protective effect of infecting HCV genotype on HIV disease
      progression.
AB  - BACKGROUND AND OBJECTIVE: Hepatitis C virus (HCV) infection is frequent in HIV
      positive subjects. We evaluated the potential impact of HCV coinfection and other
      determinants on HIV disease progression in a cohort of long-term non-progressors
      (LTNPs). STUDY DESIGN: We studied immunological and virological factors in a
      cohort of 49 LTNPs, 23 of whom progressed during the follow-up (late progressors;
      LPs). RESULTS: HCV coinfection was detected in 19/26 LTNPs and 15/23 LPs.
      Univariate analysis showed that HIV viral load was associated with disease
      progression (P=0.04), and time-to-event analysis indicated that HCV genotype 1
      significantly correlated with LTNP status (P=0.031). At multivariate analysis,
      HIV viremia at study entry remained independently associated with LTNP status
      (P=0.049). When the most represented genotypes (1 and 3a) were considered in the
      model, genotype 3a infection (P=0.034) and gender (P=0.035) emerged as
      independent variables related to HIV disease progression, whereas HIV viral load
      disappeared. CONCLUSIONS: In addition to HIV viremia, coinfection with different
      HCV genotypes and gender may affect LTNP status.

PMID- 17434340
TI  - Aptamers-based assays for diagnostics, environmental and food analysis.
AB  - Aptamers are single stranded DNA or RNA ligands which can be selected for
      different targets starting from a huge library of molecules containing randomly
      created sequences. Aptamers have been selected to bind very different targets,
      from proteins to small organic dyes. In addition to the very important aspect of
      having an unlimited source of identical affinity recognition molecules available
      due to the selection process, aptamers can offer advantages over antibodies that
      make them very promising for analytical applications. The use of aptamers as
      therapeutic tools is nowadays well established. On the contrary, the analytical
      application of aptamers in diagnostic devices or in systems for environmental and
      food analysis, is still under investigation and the scientific community still
      need further research to demonstrate the advancements brought by this new kind of
      ligands. This review will focus on these latter applications with particular
      attention to the detection of food pathogens, terrorism threat agents, thrombin
      and cytokines.

PMID- 17434341
TI  - Abnormal right ventricular tissue velocities after repair of congenital heart
      disease--implications for late outcomes.
AB  - BACKGROUND: Although repair of Tetralogy of Fallot (TOF) and transposition of the
      great arteries (TGA) has facilitated survival into adulthood, many survivors have
      residual haemodynamic abnormalities, including exercise intolerance and late
      right ventricular (RV) failure. METHODS: We studied 40 asymptomatic adult
      subjects (31.3+/-1.5 years) after congenital heart disease (CHD) surgery during
      childhood, using tissue Doppler echocardiography (TDE). We compared systolic (S')
      and diastolic (E' for early filling) RV and LV velocities, with 40 age matched
      controls (29.5+/-1.0 years). RESULTS: Both RV S' and E' velocities were
      significantly slower in the CHD group compared to controls (6.3+/-0.4 cm/s vs.
      9.3+/-0.3 cm/s; 8.5+/-0.5 cm/s vs. 10.9+/-0.4 cm/s, respectively, p<0.001 for
      both). By contrast, LV S' and E' velocities were similar in both groups.
      Interestingly, in 50% of CHD subjects where RV function was reported as 'normal',
      both RV S' and E' velocities were significantly slower compared with controls
      (6.5+/-0.6 cm/s vs. 9.3+/-0.3 cm/s, p<0.0001 and 9.4+/-0.7 cm/s vs. 10.9+/-0.4
      cm/s, p<0.05 respectively). CONCLUSIONS: RV S' and E' velocities are frequently
      abnormal in asymptomatic survivors of TOF and TGA repair, even where RV function
      appears 'normal'. Hence TDE during follow up may be a sensitive means of
      detecting pre-clinical abnormalities in RV performance.

PMID- 17434342
TI  - Large solitary fibrous tumour of the pleura: analysis of six cases.
AB  - BACKGROUND: A large solitary fibrous tumour of the pleura (SFTP) is a very rare
      occurrence. The aim of this study was to retrospectively review the clinical
      characteristics, surgical treatment and outcome of patients with a large SFTP
      operated on in our General Thoracic Surgery Unit. METHODS: We conducted a
      retrospective analysis of the clinical records of six patients who underwent
      surgery for a huge SFTP between 1998 and 2004. RESULTS: Six patients (four men
      and two women, mean age 73.3 years) with a large SFTP (mean diameter 20.3 and
      mean weight 1265 g) underwent surgery during this period with full excision of
      the tumour. Five tumours were excised together with the implantation basis, and
      in one case extended resection with pneumonectomy was performed. The presentation
      symptoms resolved in all cases after surgery. CONCLUSIONS: Despite the huge size
      of these tumours (giant SFTP), surgical resection is an acceptable method of
      treatment in elderly patients with low morbidity and mortality rates.

PMID- 17434343
TI  - Plasmodium falciparum-infected mice: more than a tour de force.
AB  - Up until recently, the relevance of Plasmodium falciparum-infected humanized mice
      for malaria studies has been questioned because of the low percentage of mice in
      which the parasite develops. Advances in the generation of new immunodeficient
      mouse strains combined with the use of protocols that modulate the innate immune
      defenses of mice have facilitated the harvesting of exoerythrocytic and
      intraerythrocytic stages of the parasite. These results renew the hope of working
      with P. falciparum in a laboratory animal and indicate that the next challenge
      (i.e. a complete parasite cycle in the same mouse, including transmission to
      mosquito) could be reached in the future.

PMID- 17434344
TI  - Illuminating Plasmodium falciparum-infected red blood cells.
AB  - The malaria parasite undergoes a remarkable series of morphological
      transformations, which underpin its life in both human and mosquito hosts. The
      advent of molecular transfection technology coupled with the ability to introduce
      fluorescent reporter proteins that faithfully track and expose the activities of
      parasite proteins has revolutionized our view of parasite cell biology. The
      greatest insights have been realized in the erythrocyte stages of Plasmodium
      falciparum. P. falciparum invades and remodels the human erythrocyte: it feeds on
      haemoglobin, grows and divides, and subverts the physiology of its hapless host.
      Fluorescent proteins have been employed to track and dissect each of these
      processes and have revealed details and exposed new paradigms.

PMID- 17434345
TI  - A preliminary study on the genetic profile of cag pathogenicity-island and other
      virulent gene loci of Helicobacter pylori strains from Turkey.
AB  - Helicobacter pylori genetic diversity affects the function and antigenicity of
      virulence factors associated with the disease outcome. Gene profile was done to
      identify the distribution of gene loci within and outside the cag pathogenicity
      island (PAI). H. pylori strains from 35 patients [21 gastritis, 14 peptic ulcer
      diseases (PUD)] were analyzed using PCR. The profile of the cag PAI was evaluated
      using primers spanning the 3' end, cagA, promoter region of the cagA, cagE, cagT,
      5' end (LEC), extreme right end, plasticity region open reading frames (ORFs),
      oipA (Hp0638) and vacA alleles. We found few intact cag PAI in the strains
      examined. Deletions were found in LEC1 (9.5% versus 14.3%), LEC2 (4.8% versus
      14.3%), cagT (33.3% versus 28.6%), cagE (28.6% versus 28.6%) and the promoter
      region of the cagA (19.0% versus 42.9%) of gastritis and PUD strains,
      respectively. The cagA gene was detectable in 57.1% of gastritis and 92.9% of PUD
      associated strains. The cagRJ region also showed deletions for many of its genes.
      The oipA (Hp0638) gene was detected in 80.9% of gastritis and in 92.9% of PUD
      strains. The plasticity region ORFs JHP912 and JHP931 were predominant in PUD
      strains. The vacA-s1a-m1a genotype was predominant in PUD, while s2m2 in
      gastritis strains. This comprehensive analysis showed deletions in several genes
      within and outside the cag PAI. However, cagA, oipA, JHP912, JHP931 and vacA-s1a
      m1a were more predominant in PUD strains than gastritis-associated strains,
      suggesting the importance of genetic diversity on the disease progression and
      clinical outcome.

PMID- 17434346
TI  - CFTR stabilizes ENaC at the plasma membrane.
AB  - CFTR was reported to regulate ENaC channel opening, decreasing ENaC activity in
      airways and increasing it in sweat ducts. We generated MDCK-I cell lines stably
      expressing tagged alphabetagammaENaC+CFTR or ENaC alone, and developed an assay
      to quantify cell-surface half-life of ENaC. Surprisingly, we found that co
      expressed CFTR stabilizes ENaC at the plasma membrane, suggesting that CFTR
      regulates ENaC stability, not just opening.

PMID- 17434347
TI  - Prolonged expiration down to residual volume leads to severe arterial hypoxemia
      in athletes during submaximal exercise.
AB  - The goal of this study was to assess the effects of a prolonged expiration (PE)
      carried out down to the residual volume (RV) during a submaximal exercise and
      consider whether it would be worth including this respiratory technique in a
      training programme to evaluate its effects on performance. Ten male triathletes
      performed a 5-min exercise at 70% of maximal oxygen consumption in normal
      breathing (NB(70)) and in PE (PE(70)) down to RV. Cardiorespiratory parameters
      were measured continuously and an arterialized blood sampling at the earlobe was
      performed in the last 15s of exercise. Oxygen consumption, cardiac frequency, end
      tidal and arterial carbon dioxide pressure, alveolar-arterial difference for O(2)
      (PA(O2) - Pa(O2)) and P(50) were significantly higher, and arterial oxygen
      saturation (87.4+/-3.4% versus 95.0+/-0.9%, p<0.001), alveolar (PA(O2)) or
      arterial oxygen pressure, pH and ventilatory equivalent were significantly lower
      in PE(70) than NB(70). There was no difference in blood lactate between exercise
      modalities. These results demonstrate that during submaximal exercise, a
      prolonged expiration down to RV can lead to a severe hypoxemia caused by a PA(O2)
      decrement (r=0.56; p<0.05), a widened PA(O2) - Pa(O2) (r=-0.85; p<0.001) and a
      right shift of the oxygen dissociation curve (r=-0.73; p<0.001).

PMID- 17434348
TI  - Role of the peripheral chemoreflex in the early stages of ventilatory
      acclimatization to altitude.
AB  - This review of ventilatory acclimatization to altitude/hypoxia (VAH) emphasizes
      the widely differing timescales that VAH is considered to encompass. The review
      concludes: (1) that early (24-48h) VAH is unlikely to arise as a reaction to the
      respiratory alkalosis that is normally associated with exposure to hypoxia; (2)
      that changes in peripheral chemoreflex function may be sufficiently rapid to
      explain early VAH; (3) that alterations in gene expression induced by hypoxia
      through the hypoxia-inducible factor (HIF) signalling pathway may underlie a
      major component of VAH; and (4) that compensatory adjustments to acid-base
      balance in response to the initial respiratory alkalosis may have more
      significance for the slower changes observed later in VAH.

PMID- 17434349
TI  - Factors associated with the technical performance of colonoscopy: An EPAGE Study.
AB  - BACKGROUND: Variations in colonoscopy practice exist, which may be related to
      healthcare quality. AIMS: To determine factors associated with three performance
      indicators of colonoscopy: complete colonoscopy, adenomatous polyp diagnosis, and
      duration. PATIENTS: Consecutive patients referred for colonoscopy from 21 centres
      in 11 countries. METHODS: This prospective observational study used multiple
      variable regression analyses to identify determinants of the quality indicators.
      RESULTS: Six thousand and four patients were included in the study. Patients from
      private, open-access centres (odds ratio: 3.17, 95% confidence interval: 1.87
      5.38) were more likely to have a complete colonoscopy than patients from public,
      gatekeeper centres. Patients from centres where over 50% of the endoscopists were
      of senior rank were roughly twice as likely to have an adenoma diagnosed, and
      longer average withdrawal duration (odds ratio: 1.08, 95% confidence interval:
      1.07-1.09) was associated with more frequent adenoma diagnoses. Patients who had
      difficulty during colonoscopy had longer durations to caecum (time ratio: 2.87,
      95% confidence interval: 2.72-3.01) and withdrawal durations (time ratio: 1.26,
      95% confidence interval: 1.18-1.33) than patients who had no difficulties.
      CONCLUSIONS: Multiple factors have been identified as being associated with key
      quality indicators. The non-modifiable factors permit the identification of
      patients who may be at greater risk of not having quality colonoscopy, while
      changes to the modifiable factors may help improve the quality of colonoscopy.

PMID- 17434350
TI  - Orbital exenteration for advanced periorbital skin cancers: 20 years experience.
AB  - PURPOSE: Orbital exenteration is a disfiguring procedure that results in a
      significant deformity which poses a reconstructive challenge, especially in
      elderly patients with significant comorbidities. We reviewed our experience of
      orbital exenteration. METHODS: A retrospective analysis was conducted identifying
      all patients undergoing orbital exenteration over a 20-year period. Patient
      demographics, tumour characteristics and reconstructive techniques used were
      recorded. RESULTS: Thirty-two patients were treated by orbital exenteration. The
      majority of these were for basal cell carcinomas (53%). Most patients (62.5%)
      were ASA grade II or more. Reconstructive techniques included split skin grafting
      (63%), forehead (25%), scalp (6%) and cervicofacial (6%) flaps. Following
      reconstruction of the exenterated orbit, 29 patients had a prosthesis. Twenty-six
      of these rated their final result with their definitive prosthesis as good.
      CONCLUSIONS: Though there are various options available for reconstruction after
      orbital exenteration, a split skin graft and orbital prosthesis provide a simple
      solution for a very difficult problem of advanced periorbital skin cancer in the
      elderly population with significant comorbidities. The final outcome is
      comparable to that of more complex flap reconstruction with comparable
      satisfaction rates.

PMID- 17434351
TI  - Mentoring the general surgeon.

PMID- 17434352
TI  - Prognostic significance of reactivation of telomerase in breast core biopsy
      specimens.
AB  - BACKGROUND: Telomerase is not expressed in most somatic tissues, but activity has
      been shown in breast carcinoma and up to 90% of solid tumors. We sought to
      determine whether activation of telomerase, as shown by immunohistochemical
      staining for human telomerase reverse transcriptase (hTERT), held prognostic
      significance in core breast biopsy specimens. METHODS: We identified women with
      atypical ductal hyperplasia (ADH) on core biopsy who either had underlying cancer
      or ADH. Immunohistochemistry with anti-hTERT antibody was performed on biopsy
      specimens, and staining was evaluated. RESULTS: Core biopsy specimens stained
      strongly with the hTERT antibody in 7 (70%) specimens with ADH on open biopsy and
      6 (86%) with underlying cancer. The difference was not statistically significant
      (P = .43). CONCLUSIONS: Our study suggests telomerase may be activated early in
      the pathogenesis of breast cancer. The immunohistochemical evaluating expression
      of hTERT does not reliably identify those patients with ADH on core biopsy who
      are likely to have cancer.

PMID- 17434353
TI  - A universal global rating scale for the evaluation of technical skills in the
      operating room.
AB  - BACKGROUND: The ideal assessment of technical skills should be defensible and
      practical. The purpose of this study was to evaluate the utility of a Global
      Rating Scale (GRS) Assessment tool of resident operating room performance.
      METHODS: Residents were assessed in the operating room on multiple occasions
      during a 6-month study period using a 9-item GRS. Data were analyzed to assess
      scale reliability and sensitivity to year of training. Feasibility was evaluated
      with a post-study questionnaire. RESULTS: Seven residents had a total of 32
      procedures assessed. One-way analysis of variance (ANOVA) showed that scores
      increased with year of training (P = .009). Reliability was excellent.
      (Cronbach's alpha .91). The post-study survey identified feedback and faculty
      interaction as strengths of this tool, but time constraint was a barrier.
      CONCLUSIONS: The GRS tool is a valid and reliable method that has the potential
      to be a practical, useful assessment tool of resident operating room performance.

PMID- 17434354
TI  - Measuring surgeon performance of sentinel lymph node biopsy in breast cancer
      treatment by cumulative sum analysis.
AB  - BACKGROUND: This study was performed to determine if surgeons' performance of
      sentinel lymph node biopsy (SLNB) for breast cancer varied with time and to
      devise a method to continuously evaluate that performance. METHODS: We
      retrospectively examined the SLNB experience of 13 community surgeons performing
      765 SLNBs and 579 concomitant axillary dissections. False-negative rates (FNRs)
      were assessed for individuals and cohorts defined by caseload. Performance with
      time was assessed using cumulative sum (CUSUM) analysis. RESULTS: Overall, the
      SLN identification rate was 94.3%, and FNR was 5.3%. Each surgeon demonstrated
      variation in identification rate and/or FNR with time. CUSUM analysis provided an
      effective means to demonstrate when surgeon variation breached performance
      standards. CONCLUSIONS: Surgeon performance of SLNB varied with time, independent
      of case load. CUSUM may prove to be a useful statistical tool to evaluate
      performance before adopting stand-alone SLNB.

PMID- 17434355
TI  - Vascular surgery training, exposure, and knowledge during general surgery
      residency: implications for the future.
AB  - BACKGROUND: Vascular surgery (VS) has been removed from the Canadian general
      surgery (GS) objectives and has become a primary certificate specialty in the
      United States, leaving its status in GS uncertain. The purpose of this study was
      to determine GS residents' perceived competence in VS and to assess their
      knowledge of VS. METHODS: GS residents at a university-based program answered (1)
      a survey of attitudes and experience in VS and (2) a short-answer examination to
      assess fundamental vascular knowledge. RESULTS: Twenty-nine of 35 residents
      participated (83%). Residents reported being inadequately trained in 10 of 13
      procedures surveyed despite 6 of these being reported as essential. Although 26
      of 29 residents reported an intention to perform vascular procedures, none
      planned on pursuing a fellowship. The mean examination score was 47%.
      CONCLUSIONS: Despite mandatory VS rotations, GS residents feel inadequately
      trained in VS and have marginal knowledge. Current trainees may lack the skills
      and abilities to deal with vascular emergencies.

PMID- 17434356
TI  - Post-bariatric panniculectomy: pre-panniculectomy body mass index impacts the
      complication profile.
AB  - BACKGROUND: Morbid obesity continues to increase in the United States, which
      accounts for the increase in bariatric procedures performed. After these patients
      experience massive weight loss, many are left with a redundant pannus that poses
      physical limitations and psychosocial disturbances. An increasing proportion of
      bariatric patients are returning for body-contouring procedures. METHODS: This is
      a retrospective cohort study set in a tertiary care center. We evaluated 126 post
      bariatric panniculectomies performed over a 3-year period. Perioperative and
      postoperative data were collected through chart review. Descriptive and
      inferential analyses were performed using SPSS 11.0. RESULTS: Ninety-six percent
      of patients were female. Mean age of the population was 42 (+/-12). The average
      post-bariatric weight loss and pre-panniculectomy weight were 53 (+/-16) kg and
      78 (+/-14) kg, respectively. Complication rates were as follows: seroma 17%,
      hematoma 13%, surgical site infection (SSI) 17%, transfusion 6%, skin
      breakdown/necrosis 11%, and re-exploration 11%. Forty percent of patients
      experienced a complication. Using multivariate logistic regression, we evaluated
      age, pre-panniculectomy body mass index (BMI), American Society of
      Anesthesiologists (ASA) class, specimen weight, and operative duration; only pre
      panniculectomy BMI was an independent predictor for developing a postoperative
      complication (odds ratio 3.3, confidence interval 1.2 to 8.4, P < .01).
      CONCLUSIONS: Post-bariatric patients who have sustained significant weight loss
      report subjective improvement after panniculectomy. Even though this population
      has experienced significant weight loss, they are still at an increased risk for
      postoperative complications. Maximal reduction in BMI should be stressed to these
      patients in order to reduce their risk of complications following panniculectomy.

PMID- 17434357
TI  - The impact of nodal isolated tumor cells on survival of breast cancer patients.
AB  - BACKGROUND: Isolated tumor cells (ITCs), often detectable only with
      immunohistochemical techniques, have an unknown significance in the prognosis of
      breast cancer. The American Joint Committee on Cancer guidelines classify such
      patients as N0 (immunohistochemistry +), staging them with node-negative
      patients. We sought to further elucidate the impact of ITCs on survival. METHODS:
      We conducted a retrospective review of all women at our institution with breast
      cancer from 1996 to 2005. Of 514 patients, 16 had isolated tumor cells detected
      only with immunohistochemical staining. Survival then was compared with
      historical survival rates for women with node-free disease. RESULTS: The 16 women
      with N0 (i+) disease had stage I or II disease. There was no documented
      recurrence among these women, with an average follow-up period of 2.5 years.
      CONCLUSIONS: Our data suggest that ITCs detected in lymph nodes do not adversely
      impact survival or disease-free survival compared with women with node-negative
      disease. Larger studies will be required to confirm these findings.

PMID- 17434358
TI  - Laparoscopic colon surgery in community practice.
AB  - BACKGROUND: The benefits of laparoscopic colon surgery have been shown in the
      literature. More recently, the oncologic outcomes have been shown to be similar
      in the laparoscopic group when compared with open colon surgery for colon cancer.
      However, most of the published literature is from university/academic
      institutions. There is limited literature on laparoscopic colon surgery from a
      community hospital. METHODS: A retrospective chart review was conducted of 62
      laparoscopic colon surgeries from a single surgeon's practice in a community
      hospital from October 27, 2003, to August 31, 2006. The laparoscopic approach was
      performed on patients with benign and curative colon cancer. The primary outcome
      measures were length of operating room times, pathologic results, length of
      hospital stay, and complication rates. RESULTS: Of the 62 laparoscopic patients,
      there were 9 converted patients (14% conversion rate). There were no
      perioperative deaths, and no anastomotic leaks. The average length of operating
      room time was 190 minutes (range, 96-295 min). The median length of hospital stay
      was 4 days (range, 3-17 d). There were 40 laparoscopic patients for colon cancer.
      The resection margins all were negative, and the mean number of lymph nodes in
      the resected specimen was 17 (range, 5-37). The overall complication rate was
      18%. CONCLUSIONS: This study showed that laparoscopic colon surgery is
      technically feasible in a community hospital. The results from this study are
      similar to the published literature from university/academic institutions.

PMID- 17434359
TI  - An 18-year review of open and laparoscopic splenectomy for idiopathic
      thrombocytopenic purpura.
AB  - BACKGROUND: Laparoscopic splenectomy has become the preferred surgical procedure
      for the management of idiopathic thrombocytopenic purpura (ITP). However, there
      studies have directly compared the incidence of recurrent ITP secondary to missed
      accessory spleens in open versus laparoscopic splenectomy. METHODS: Open and
      laparoscopic splenectomies performed for ITP at 4 sites over 18 years were
      analyzed. The incidence of recurrent disease secondary to missed accessory
      spleens was compared between the open and laparoscopic splenectomy groups.
      RESULTS: A total of 105 splenectomies (54 open/51 laparoscopic) were performed.
      Accessory spleens were identified in 6 laparoscopic and 6 open cases (P = .57).
      Recurrent disease occurred in 27.6% of open and 14.6% of laparoscopic cases (P =
      .222). There were no cases of recurrent ITP secondary to a missed accessory
      spleen in either group. CONCLUSIONS: The incidence of missed accessory spleens
      causing recurrent disease is similar when splenectomy is performed either open or
      laparoscopically.

PMID- 17434360
TI  - The value of diverting loop ileostomy on the high-risk colon and rectal
      anastomosis.
AB  - INTRODUCTION: The need for diverting loop ileostomies to protect high-risk
      anastomoses has been questioned recently by several authors. This study was
      designed to evaluate the potential benefits and complications of diverting loop
      ileostomies in a high-risk anastomosis population. METHODS: Ninety-four
      consecutive patients undergoing diverting loop ileostomy were evaluated from a
      prospective database between 2003 and 2006. Criteria for diversion were:
      anastomosis less than 5 cm from the anal verge, previous pelvic radiation
      therapy, obstruction, and infection. Data regarding patient demographics,
      underlying pathology, anastomotic problems, and ileostomy-related problems were
      gathered. RESULTS: Indications for surgery were malignancy (n = 40), ulcerative
      colitis (n = 37), acute diverticulitis (n = 12), perirectal fistulas (n = 3), and
      familial polyposis (n = 2). There were 5 anastomotic complications. One required
      permanent stoma and 4 required delay in diverting ileostomy closure but no other
      intervention. Ileostomy-related problems were limited to minor stoma and pouch
      complaints requiring stoma nurse evaluation (n = 23), dehydration requiring
      outpatient (n = 8) or inpatient (n = 4) intravenous fluids, stricture at stoma
      closure site (n = 2), and bleeding at stoma closure site (n = 1). Four stoma site
      hernias (4.3%) have been identified to date. CONCLUSION: The use of diverting
      loop ileostomy in patients undergoing colon and rectal surgery with high-risk
      anastomoses is beneficial. Their selected use has resulted in a 1% anastomotic
      loss rate with an acceptably low rate of complications related to the ileostomy.

PMID- 17434361
TI  - The impact of a formal mentoring program for minimally invasive surgery on
      surgeon practice and patient outcomes.
AB  - BACKGROUND: Surgeons need a process by which to safely introduce new procedures,
      such as minimally invasive surgery (MIS), into practice. Emerging evidence would
      suggest that an effective strategy is the implementation of a mentorship program.
      This study analyzed the effect of mentoring on a single institution's advanced
      MIS practice. METHODS: We analyzed clinical outcomes by completing a
      retrospective review of patient charts 1 year before and 1 year after the
      recruitment of a fellowship-trained advanced MIS surgeon in July 2004 whose job
      description included facilitating the introduction of advanced gastrointestinal
      MIS. RESULTS: A total of 7 general surgeons were mentored at 1 site. After 1 year
      of intense mentoring, the number of surgeons completing >12 cases/y increased
      from 2 to 4, and the number of advanced MIS cases completed (excluding mentored
      ones) increased from 35 to 102. Fifty-three cases (52% of total) were formally
      mentored. Total conversions to open surgery decreased from 14.3% to 6.4% (P =
      .12). The number of colorectal resections increased from 11 to 92 (P = .0027).
      Intraoperative complications were not significantly decreased, eg, from 17.1% to
      7.1% (P = .06). Postoperative complications remained unchanged (15.0% to 16.5%).
      CONCLUSIONS: Surgeons and the institutions in which they work have a duty to
      adopt advanced MIS techniques in a safe and appropriate manner. We believe our
      data demonstrate that a mentorship program is an effective strategy for safely
      introducing advanced MIS into practice.

PMID- 17434362
TI  - A needs-assessment study for continuing professional development in advanced
      minimally invasive surgery.
AB  - BACKGROUND: The ideal continuing professional development (CPD) model to transfer
      advanced minimally invasive surgical (MIS) skills to surgeons in practice has not
      yet been determined. METHODS: A survey of general surgeons practicing in Alberta
      was conducted to determine attitudes toward CPD with a focus on MIS colon
      surgery. Two separate mailings of the survey were conducted in both hard copy and
      e-mail format. Data were collected and analyzed. RESULTS: Seventy-one of 92
      surveys were returned, yielding a response rate of 77%. The majority (62%) of
      surgeons had received their training while in practice. The most prevalent form
      of CPD was short courses, with 82% of surgeons having attended at least 1 short
      course in MIS. When directly comparing short courses with mentorship, 69% of
      respondents rated courses as less helpful, whereas 21% thought they were
      equivalent to mentorship. Sixty-one percent of surgeons are interested in a
      comprehensive approach, such as a mini-fellowship, to learning laparoscopic
      colorectal surgery. CONCLUSIONS: General surgeons want access to different
      modalities of training, including both mentorship experiences and short courses.
      They are willing to take time away from their practices to learn new MIS skills.
      The best way to provide CPD to practicing surgeons is likely through a
      combination of teaching interventions, including courses, mentoring
      relationships, and the application of new technologies.

PMID- 17434363
TI  - Martius flap: an adjunct for repair of complex, low rectovaginal fistula.
AB  - BACKGROUND: Complex, rectovaginal fistula (RVF) are uncommon but difficult
      therapeutic problems. Local repair and flap advancement techniques have a high
      incidence of recurrence with poor functional outcomes. Transperineal repair with
      anal sphincter reconstruction, when indicated, and placement of a Martius flap
      (bulbocavernosus pedicled transplant) result in improved rates of repair and
      better functional outcomes. METHODS: A consecutive series of patients were
      retrospectively reviewed from a prospective database between 2002 and 2006. Data
      were gathered from 2 colon- and rectal-specialty practices. Patient demographics
      and operative and functional outcomes were documented. RESULTS: Sixteen patients
      with a mean age of 39.5 years (17-62) were treated. Etiology of the fistula was
      obstetric (9), cryptoglandular (5), and Crohn's disease (2). They had undergone a
      mean of 1.5 (0-4) prior repairs, and 6 had a preexisting diverting stoma before
      repair. Preoperatively, anal sphincter disruption was identified in 11 patients,
      and fecal incontinence was identified in 5 patients all with anal sphincter
      disruption. Dyspareunia was identified in 1 of 13 sexually active patients
      preoperatively. At a mean follow-up of 75 weeks (24-190), 1 recurrent fistula was
      identified (6.2%). Stomas were reversed in all patients. Two patients complained
      of fecal incontinence postoperatively. Five patients had dyspareunia
      postoperatively (5/16, 31%). One patient had a labial wound complication
      requiring local wound care. CONCLUSION: Selected complex RVF can be reliably
      repaired with good functional outcomes using the Martius flap with anal sphincter
      reconstruction. Persistent or recurrent fecal incontinence and dyspareunia are
      common sequela of the underlying perineal injury and repair. No acute or delayed
      morbidity related to the Martius flap was identified.

PMID- 17434364
TI  - Contrast-enhanced breast magnetic resonance imaging: the surgical perspective.
AB  - BACKGROUND: Contrast-enhanced breast magnetic resonance imaging (MRI) has shown
      excellent sensitivity (93%) for breast malignancies. The clinical role and value
      of MRI for the breast surgeon remains unresolved and controversial. METHODS: A
      retrospective review of clinical and imaging records was undertaken for 79
      surgical patients evaluated by MRI as part of their initial assessment. RESULTS:
      Of 79 patients, 71 (90%) had dense mammograms, 64 (81%) had known primary breast
      cancer (BrCA), 42 (53%) had a family history of BrCA, and 8 (10%) had known
      breast atypia. MRI identified a larger than clinically suspected BrCA size in 10
      (16%) patients and greater BrCA extent in 26 (41%) patients. Of 15 non-BrCA
      patients, 10 (67%) had a biopsy after the MRI with identification of BrCA in 6
      (40%) patients. Overall, there were 20 MRI-initiated core biopsies, of which 14
      (70%) identified BrCA. Of 70 BrCA patients, 13 (19%) had neoadjuvant
      chemotherapy, 35 (50%) had breast-conserving surgery, 36 (51%) had total
      mastectomy, and 14 (22%) had bilateral total mastectomy. MRI had good pathology
      correlation in 56 of 62 (90%) patients. In patients with known BrCA (by core
      biopsy), none of the 29 breast-conserving surgery resections undertaken after MRI
      had a positive margin or required re-excision. CONCLUSIONS: MRI is very accurate
      for BrCA evaluation, both for lesion size and extent. With good collaboration
      between the radiologist and surgeon, MRI is a powerful 3-dimensional and
      communication tool for the breast surgeon and the patient.

PMID- 17434365
TI  - Utility of the cleft lift procedure in refractory pilonidal disease.
AB  - BACKGROUND: Refractory pilonidal disease is a problem. We wished to show the
      utility of the cleft lift procedure in solving nonhealing. METHODS: We selected a
      subset of challenging cases for this study. The subset included all patients
      referred with persistent open wounds despite at least 2 prior pilonidal surgeries
      elsewhere. RESULTS: The 69 patients had undergone 223 surgeries (average, 3) and
      endured open wounds for a sum of 365 years (average, 5). All patients we
      contacted were healed after a single cleft lift surgery with 3 exceptions. Two
      patients required 2 lifts before healing and 1 patient required 3 lifts.
      CONCLUSIONS: The cleft lift procedure gave excellent results in patients with
      refractory pilonidal disease.

PMID- 17434366
TI  - Aggressive pancreatic resection for primary pancreatic neuroendocrine tumor: is
      it justifiable?
AB  - BACKGROUND: Benign and malignant pancreatic neuroendocrine tumors (PNETs) are
      rare, and long-term outcome is generally poor without surgical intervention. The
      aim of the study was to assess whether aggressive pancreatic resection is
      justifiable for patients with PNET. METHODS: All consecutive patients who had
      undergone major pancreatic resection from January 1997 through January 2005 were
      reviewed and analyzed. RESULTS: There were 33 patients (16 male and 17 female)
      with a mean age of 53 years. Five patients had multiple endocrine neoplasms
      syndrome, and 1 patient had von Hippel-Lindau syndrome. There were 20 benign (9
      functional) and 13 malignant (6 functional) neoplasms. Mean tumor size was 4.2
      cm, and multiple tumors were noted in 10 patients. Eight patients (25%) underwent
      pancreticoduedenectomy, and 25 patients (76%) underwent distal pancreatectomy
      (extended distal pancreatectomy in 4 and splenectomy in 20 patients). Regional
      lymph node involvement was present in 10 patients (30%), and 6 patients (18%) had
      liver metastasis. Four patients (12%) underwent concurrent resection of other
      organs because of disease extension. Median intraoperative blood loss was 500 mL.
      Perioperative morbidity was 36%, and mortality was 3%. Symptomatic palliation was
      complete in 93% (14.15 patients) and partial in 1 patient because of
      nonresectable hepatic disease. Median hospital stay was 11.5 days. After median
      follow-up of 36 months, there were no local recurrences. The 1-, 3-, and 5-year
      overall survival rates for patients with benign versus malignant neoplasms were
      100% vs. 92%, 89% vs. 64%, and 89% vs 36% (P = .01), respectively. The 1-, 3-,
      and 5-year disease progression rates for patients with malignant neoplasms were
      13%, 63%, and 100%, respectively (P < .0001). CONCLUSIONS: Aggressive pancreatic
      resection for PNET can be performed with low perioperative mortality and
      morbidity. Unlike available nonoperative therapy, this approach offers an
      excellent means of symptomatic palliation and local disease control. In patients
      with malignant PNET, metastatic recurrence is not uncommon and will usually
      require additional multimodality therapy. When possible, an aggressive approach
      to PNET is justified to optimize palliation and survival.

PMID- 17434367
TI  - Accuracy of pathologic examination in detection of complete response after
      chemoradiation for esophageal cancer.
AB  - BACKGROUND: Although a substantial proportion of patients undergoing neoadjuvant
      chemoradiation for invasive esophageal cancer develop a pathologic complete
      response (pCR), these patients nonetheless have a poor 5-year survival rate. We
      hypothesized that routine pathologic examination fails to identify some residual
      cancer. METHODS: Patients undergoing esophagectomy for cancer at 2 tertiary care
      centers were identified. Archived tumor blocks were retrieved for patients with
      pCR, sectioned at 50-mum intervals and reexamined for residual cancer. RESULTS:
      Seventy patients underwent neoadjuvant chemoradiation. Tumor blocks were
      available for 23 of 26 complete responders. A total of 159 blocks were
      reexamined. One patient was found to have a possible focus of residual invasive
      adenocarcinoma versus high-grade dysplasia. The remaining 22 patients had no
      residual disease. CONCLUSIONS: A more aggressive examination protocol for
      postchemoradiation esophagectomy specimens may not result in significant
      upstaging. Inadequate pathologic examination is likely not a major factor in the
      suboptimal survival in patients with pCR.

PMID- 17434368
TI  - Sentinel node staging of primary melanoma by the "10% rule": pathology and
      clinical outcomes.
AB  - BACKGROUND: Surgical staging of clinically node-negative primary melanoma
      involves identification and removal of "sentinel" lymph nodes (SLNs). Although
      some suggest removal of only the "hottest" SLN, the "10% rule" dictates that
      nodes are removed until the background count is 10% or less of the count of the
      "hottest" node. METHODS: To determine the utility of the 10% rule, a university
      database of clinically node-negative melanomas surgically staged by using this
      rule was examined. RESULTS: Twenty-two of 177 cases (12.5%; 15% of T2 and T3
      lesions) were SLN positive. Among the SLN-positive cases, use of the rule
      resulted in removal of 21 additional nodes, 7 of which contained tumor. In 3
      cases (14%), the positive SLN was not the "hottest" node. At 49 months of mean
      follow-up time, overall survival was 63% for SLN-positive patients versus 92% for
      SLN-negative patients (P = .01). CONCLUSIONS: Sentinel node staging of melanoma
      by the 10% rule provides significant prognostic information and a modest increase
      in tumor detection compared with removal of only the "hottest" node.

PMID- 17434369
TI  - The surgical management of rectal cancer: a comparison of treatment methods and
      outcomes over 2 time periods in the same geographic region.
AB  - BACKGROUND: Preoperative radiotherapy combined with total mesorectal excision
      (TME) has provided excellent local control in the treatment of rectal cancer.
      This study is a review of patients treated at our regional cancer center from
      1998 to 2004. The results were compared with a similar study carried out in our
      region from 1988 to 1998 to determine any changes in treatment methods,
      recurrence rates, and survival. METHODS: A retrospective review of 448 patients
      treated with definitive surgery for rectal cancer was conducted. Patient factors
      analyzed included sex, age, type of surgery, and adjuvant strategy. Tumor factors
      analyzed included level, stage, and grade. The presence of local recurrence was
      recorded and overall survival was determined. RESULTS: The local recurrence rate
      was 8.3% compared with 12.7% in the previous study. Patients treated with
      preoperative radiotherapy had a recurrence rate of 3.7%. The type of surgical
      therapy had no significant effect on local recurrence. There was no significant
      change in overall survival between the present study and the previous one.
      CONCLUSION: Preoperative radiotherapy is used more frequently in our region and
      has resulted in a decrease in the local recurrence rate compared to our previous
      retrospective review. There was no change in local recurrence seen in those
      patients treated with operative management alone. This study supports the use of
      preoperative radiotherapy in the management of rectal cancer.

PMID- 17434370
TI  - Dr. Henry B. Luhn: North Pacific Surgical Association founder and pioneer surgeon
      in early Spokane.

PMID- 17434371
TI  - Trauma team activation: simplified criteria safely reduces overtriage.
AB  - BACKGROUND: Our current trauma triage system uses patient and scene variables
      within a 3-tiered trauma response system. Our purpose was to evaluate the
      accuracy of the current system and to identify the most reliable variables for
      trauma triage. METHODS: This was a retrospective review at a level II trauma
      center. Multivariate logistic regression was used to identify independent
      predictors of the need for any urgent emergency department procedure or operative
      intervention. The current triage system was analyzed and compared with a proposed
      simplified system. RESULTS: There were 1495 consecutive trauma admissions
      identified, the majority (88%) were blunt mechanism. Urgent emergency department
      interventions were required in 11%, and 4% required emergent surgery. Logistic
      regression demonstrated that prehospital Glasgow Coma Score <14 (odds ratio [OR]
      9.7), hypotension (OR 3.3), altered respiratory effort (OR 4.6), and penetrating
      truncal injury (OR 10.8) independently predicted the need for urgent intervention
      (all P < .01). The current system undertriaged only 1% but overtriaged 51% of
      patients. A simplified triage system using these 4 variables significantly
      decreased overtriage and reliably identified patients with severe injury.
      CONCLUSIONS: A simplified triage system using only highly predictive variables
      can safely decrease the high rate of overtriage of trauma patients.

PMID- 17434372
TI  - Equestrian injuries: incidence, injury patterns, and risk factors for 10 years of
      major traumatic injuries.
AB  - BACKGROUND: Horseback riding is more dangerous than motorcycle riding, skiing,
      football, and rugby. The purpose of this study was to identify the incidence and
      injury patterns, as well as risk factors associated with severe equestrian
      trauma. METHODS: All patients with major equestrian injuries (injury severity
      score > or = 12) admitted between 1995 and 2005 were reviewed. A 46-question
      survey outlining potential rider, animal, and environmental risk factors was
      administered. RESULTS: Among 7941 trauma patients, 151 (2%) were injured on
      horseback (mean injury severity score, 20; mortality rate, 7%). Injuries included
      the chest (54%), head (48%), abdomen (22%), and extremities (17%). Forty-five
      percent required surgery. Survey results (55%) indicated that riders and horses
      were well trained, with a 47% recidivism rate. Only 9% of patients wore helmets,
      however, 64% believed the accident was preventable. CONCLUSIONS: Chest trauma
      previously has been underappreciated. This injury pattern may be a result of
      significant rider experience. Helmet and vest use will be targeted in future
      injury prevention strategies.

PMID- 17434373
TI  - Diagnosis and management of blunt pancreatic ductal injury in the era of high
      resolution computed axial tomography.
AB  - BACKGROUND: Blunt pancreatic ductal injury is an uncommon but potentially morbid
      injury that can be difficult to diagnose and manage. Computed axial tomography
      (CAT) scan has historically been unreliable for the detection of ductal injury,
      but the advent of high-resolution CAT should improve diagnostic accuracy.
      METHODS: From our prospectively maintained trauma registry, consecutive patients
      who had a diagnosis of blunt pancreatic injury with or without a subsequent
      laparotomy during the time period from January 1995 through December 2004 were
      retrospectively reviewed. Pancreatic ductal injury was treated exclusively with
      distal pancreatic resection (DPR) without adjunctive endoscopic retrograde
      cholangiopancreatography or magnetic resonance cholangiopancreatography. RESULTS:
      Of 50 patients with blunt pancreatic injury, 33 patients had both preoperative
      CAT scan and laparotomy. Although the CAT scan interpretation and operative
      findings corresponded precisely for all pancreatic injuries in only 55% of cases,
      CAT scan was 91% sensitive and 91% specific for identifying pancreatic ductal
      injury. Eleven patients with confirmed pancreatic ductal injury underwent DPR.
      There were no postoperative pancreas-related deaths and only 1 pancreas-related
      complication among survivors, a patient with a low-output pancreatic fistula that
      resolved after 5 weeks. CONCLUSIONS: Blunt pancreatic ductal injury may be
      accurately diagnosed with preoperative CAT scan, without adjunctive endoscopic
      retrograde cholangiopancreatography or magnetic resonance
      cholangiopancreatography, and is effectively and safely treated with DPR.

PMID- 17434374
TI  - Effect of patient positioning on intra-abdominal pressure monitoring.
AB  - BACKGROUND: Intra-abdominal hypertension affects multiple organ systems. Current
      measurement standard requires supine positioning, which jeopardizes patient
      safety by increasing the risk for ventilator-associated pneumonia. This study
      evaluated the relationship between intra-abdominal pressure (IAP) and head-of-bed
      (HOB) positioning in critically ill intubated patients. METHODS: IAP measurements
      were performed using intravesical catheters with manometry. IAP was measured in a
      range of patient HOB increases from 0 degrees to 45 degrees. Multivariable
      generalized estimating equation modeling was performed to describe the
      relationship between IAP and HOB positioning. RESULTS: Three hundred (300)
      observations were performed on 37 patients. In multivariable modeling, HOB
      increase was significantly associated with IAP. Body mass index, positive end
      expiratory pressure, temperature, and diagnostic category were significant in
      this model, whereas age and Riker sedation score were not. CONCLUSIONS: There is
      a significant, positive association between IAP and HOB positioning in critically
      ill patients. Clinically relevant changes in IAP occur at HOB increases >20
      degrees.

PMID- 17434375
TI  - Latissimus dorsi free flaps for complex ischiosacral defects.
AB  - BACKGROUND: Free tissue transfer for coverage of complex wounds in the ischial
      and sacral area can be limited by the lack of adequate recipient vessels.
      METHODS: We reviewed the records of 3 patients seen between August 2002 and
      December 2005 who underwent free tissue transfer to ischiosacral defects.
      RESULTS: Two patients were quadriplegic, and 1 patient was ambulatory. The
      gluteal vessels were used as recipients in 2 patients, and 1 patient had an
      arteriovenous loop to the femoral vessels. All flaps were successful and all
      wounds healed. CONCLUSIONS: A free latissimus flap to the ischiosacral area can
      be effective, and both local (gluteal) and regional (femoral) vessels can serve
      as recipient vessels.

PMID- 17434376
TI  - Bilateral anterior abdominal bipedicle flap with permanent prosthesis for the
      massive abdominal skin-grafted hernia.
AB  - BACKGROUND: Fascial closure after damage control or decompression laparotomy is
      not always possible. The result is a ventral hernia covered with skin grafts.
      Massive hernias impair bowel, bladder, and respiratory function and are
      displeasing aesthetically. Most repair methods provide inadequate closure of
      large full-thickness abdominal wall defects. We describe our method of repair
      using bilateral anterior abdominal bipedicle flaps over permanent mesh. METHODS:
      We reviewed 6 patients who underwent this repair method. This staged repair first
      involves flap elevation followed by delay. In the next stage, the hernia skin
      graft is excised, mesh is placed, and flaps are advanced to midline to cover the
      mesh. RESULTS: The average hernia size was 885 +/- 274 cm2 (28-cm wide x 31-cm
      vertical), with a range of up to 37-cm wide. An average of 3 surgeries were
      required for closure, with a mean hospital stay of 22 days. No patients developed
      hernia recurrence with a mean follow-up period of 23 months. CONCLUSIONS: This
      method provides successful and durable closure of massive skin-grafted hernias.

PMID- 17434377
TI  - Strengthening clinical research in India.

PMID- 17434378
TI  - Medical students should be taught about rape.

PMID- 17434379
TI  - Taking childhood hearing loss seriously.

PMID- 17434380
TI  - Raltegravir: a new antiretroviral class for salvage therapy.

PMID- 17434381
TI  - Mycobacterium bovis tuberculosis: forgotten, but not gone.

PMID- 17434382
TI  - Human resources in developing countries.

PMID- 17434383
TI  - Young people seeking mental-health care.

PMID- 17434384
TI  - Research challenges to improve maternal and child survival.

PMID- 17434385
TI  - Do patients understand risk?

PMID- 17434386
TI  - Clinical update: atrial septal defect in adults.

PMID- 17434388
TI  - William McKenna.

PMID- 17434390
TI  - Stroke-unit care for patients with acute stroke.

PMID- 17434391
TI  - Stroke-unit care for patients with acute stroke.

PMID- 17434392
TI  - Trends in diabetes.

PMID- 17434393
TI  - Trends in diabetes.

PMID- 17434394
TI  - Hydroxychloroquine in systemic lupus erythematosus.

PMID- 17434395
TI  - Trends in diabetes.

PMID- 17434396
TI  - Trends in diabetes.

PMID- 17434397
TI  - Compensation for diethylstilbestrol injury.

PMID- 17434399
TI  - Use of high-sensitivity CRP to predict first cardiovascular events.

PMID- 17434400
TI  - Locally acquired hepatitis E in chronic liver disease.

PMID- 17434401
TI  - Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in
      treatment-experienced patients with multidrug-resistant virus: a phase II
      randomised controlled trial.
AB  - BACKGROUND: Raltegravir (MK-0518) is an HIV-1 integrase inhibitor with potent in
      vitro activity against HIV-1 strains including those resistant to currently
      available antiretroviral drugs. The aim of this study was to assess the safety
      and efficacy of raltegravir when added to optimised background regimens in HIV
      infected patients. METHODS: HIV-infected patients with HIV-1 RNA viral load over
      5000 copies per mL, CD4 cell counts over 50 cells per muL, and documented
      genotypic and phenotypic resistance to at least one nucleoside reverse
      transcriptase inhibitor, one non-nucleoside reverse transcriptase inhibitor, and
      one protease inhibitor were randomly assigned to receive raltegravir (200 mg, 400
      mg, or 600 mg) or placebo orally twice daily in this multicentre, triple-blind,
      dose-ranging, randomised study. The primary endpoints were change in viral load
      from baseline at week 24 and safety. Analyses were done on a modified intention
      to-treat basis. This trial is registered with ClinicalTrials.gov, with the number
      NCT00105157. FINDINGS: 179 patients were eligible for randomisation. 44 patients
      were randomly assigned to receive 200 mg raltegravir, 45 to receive 400 mg
      raltegravir, and 45 to receive 600 mg raltegravir; 45 patients were randomly
      assigned to receive placebo. One patient in the 200 mg group did not receive
      treatment and was therefore excluded from the analyses. For all groups, the
      median duration of previous antiretroviral therapy was 9.9 years (range 0.4-17.3
      years) and the mean baseline viral load was 4.7 (SD 0.5) log10 copies per mL.
      Four patients discontinued due to adverse experiences, three (2%) of the 133
      patients across all raltegravir groups and one (2%) of the 45 patients on
      placebo. 41 patients discontinued due to lack of efficacy: 14 (11%) of the 133
      patients across all raltegravir groups and 27 (60%) of the 45 patients on
      placebo. At week 24, mean change in viral load from baseline was -1.80 (95% CI 
      2.10 to -1.50) log10 copies per mL in the 200 mg group, -1.87 (-2.16 to -1.58)
      log10 copies per mL in the 400 mg group, -1.84 (-2.10 to -1.58) log10 copies per
      mL in the 600 mg group, and -0.35 (-0.61 to -0.09) log(10) copies per mL for the
      placebo group. Raltegravir at all doses showed a safety profile much the same as
      placebo; there were no dose-related toxicities. INTERPRETATION: In patients with
      few remaining treatment options, raltegravir at all doses studied provided better
      viral suppression than placebo when added to an optimised background regimen. The
      safety profile of raltegravir is comparable with that of placebo at all doses
      studied.

PMID- 17434402
TI  - Cluster of human tuberculosis caused by Mycobacterium bovis: evidence for person
      to-person transmission in the UK.
AB  - BACKGROUND: Despite a recent resurgence in the incidence of bovine tuberculosis
      in UK cattle herds, no associated rise in the number of cases in man has been
      noted. Disease due to human Mycobacterium bovis infection usually occurs in older
      patients, in whom drinking unpasteurised milk in the past is the probable source
      of infection. Person-to-person transmission is very rare. METHODS: After
      identification of two epidemiologically-linked cases of human M bovis infection
      through routine laboratory and surveillance activities, all patients identified
      with M bovis infection in the Midlands from 2001-05 (n=20) were assessed by DNA
      fingerprinting (MIRU-VNTR and spoligotyping), with additional interviews for
      patients with a clustered strain. FINDINGS: A cluster of six cases was
      identified. All clustered cases were young and UK-born; five patients had
      pulmonary disease, and one patient died due to M bovis meningitis, with four
      patients possessing factors predisposing to tuberculosis. All patients had common
      social links through visits to bars in two different areas. With the exception of
      the first case, there was an absence of zoonotic links or consumption of
      unpasteurised dairy products, suggesting that person-to-person transmission had
      occurred. INTERPRETATION: This report of several instances of M bovis
      transmission between people in a modern urban setting emphasises the need to
      maintain control measures for human and bovine tuberculosis. Transmission and
      subsequent disease was probably due to a combination of host and environmental
      factors. Prospective surveillance and DNA fingerprinting identified the cluster,
      enabling health protection teams to set up control measures and prevent further
      transmission.

PMID- 17434403
TI  - Health workers and vaccination coverage in developing countries: an econometric
      analysis.
AB  - BACKGROUND: Vaccine-preventable diseases cause more than 1 million deaths among
      children in developing countries every year. Although health workers are needed
      to do vaccinations, the role of human resources for health as a determinant of
      vaccination coverage at the population level has not been investigated. Our aim
      was to test whether health worker density was positively associated with
      childhood vaccination coverage in developing countries. METHODS: We did cross
      country multiple regression analyses with coverage of three vaccinations--measles
      containing vaccine (MCV); diphtheria, tetanus, and pertussis (DTP3); and
      poliomyelitis (polio3)--as dependent variables. Aggregate health worker density
      was an independent variable in one set of regressions; doctor and nurse densities
      were used separately in another set. We controlled for national income per
      person, female adult literacy, and land area. FINDINGS: Health worker density was
      significantly associated with coverage of all three vaccinations (MCV p=0.0024;
      DTP3 p=0.0004; polio3 p=0.0008). However, when the effects of doctors and nurses
      were assessed separately, we found that nurse density was significantly
      associated with coverage of all three vaccinations (MCV p=0.0097; DTP3 p=0.0083;
      polio3 p=0.0089), but doctor density was not (MCV p=0.7953; DTP3 p=0.7971; polio3
      p=0.7885). Female adult literacy was positively associated, and land area
      negatively associated, with vaccination coverage. National income per person had
      no effect on coverage. INTERPRETATION: A higher density of health workers
      (nurses) increases the availability of vaccination services over time and space,
      making it more likely that children will be vaccinated. After controlling for
      other determinants, the level of income does not contribute to improved
      immunisation coverage. Health workers can be a major constraining factor on
      vaccination coverage in developing countries.

PMID- 17434404
TI  - A man with a hole in his head.

PMID- 17434405
TI  - Autosomal dominant polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease is the most prevalent, potentially
      lethal, monogenic disorder. It is associated with large interfamilial and
      intrafamilial variability, which can be explained to a large extent by its
      genetic heterogeneity and modifier genes. An increased understanding of the
      disorder's underlying genetic, molecular, and cellular mechanisms and a better
      appreciation of its progression and systemic manifestations have laid out the
      foundation for the development of clinical trials and potentially effective
      treatments.

PMID- 17434406
TI  - Mental health of young people: a global public-health challenge.
AB  - Mental disorders account for a large proportion of the disease burden in young
      people in all societies. Most mental disorders begin during youth (12-24 years of
      age), although they are often first detected later in life. Poor mental health is
      strongly related to other health and development concerns in young people,
      notably lower educational achievements, substance abuse, violence, and poor
      reproductive and sexual health. The effectiveness of some interventions for some
      mental disorders in this age-group have been established, although more research
      is urgently needed to improve the range of affordable and feasible interventions,
      since most mental-health needs in young people are unmet, even in high-income
      countries. Key challenges to addressing mental-health needs include the shortage
      of mental-health professionals, the fairly low capacity and motivation of non
      specialist health workers to provide quality mental-health services to young
      people, and the stigma associated with mental disorder. We propose a population
      based, youth focused model, explicitly integrating mental health with other youth
      health and welfare expertise. Addressing young people's mental-health needs is
      crucial if they are to fulfil their potential and contribute fully to the
      development of their communities.

PMID- 17434407
TI  - Global burden of childhood hearing impairment and disease control priorities for
      developing countries.

PMID- 17434408
TI  - Bronchopulmonary sequestration: a differential diagnosis in young adults for
      recurrent pneumonia.

PMID- 17434410
TI  - Approaches to the study of higher cognitive functions related to creativity in
      nonhuman animals.
AB  - Fundamental to creativity is prior knowledge and learning capability. One can be
      creative only to the extent that one's prior knowledge and learning abilities
      enable. Many of the mental functions of humans that are affected by
      neuropathology involve levels of learning ability that supercede those used by
      most animal researchers. Yet there is literature showing that there are
      similarities in structure and function in the cerebrum within class Mammalia and
      that nonhuman animals are capable of higher levels of learning than those
      typically studied by neuroscientists. Reviews of abstracts from the 2005 meeting
      of the Society for Neuroscience reveal that most neurobehavioral research with
      animals has involved relatively low levels of learning ability. Thomas's [R.K.
      Thomas, Brain, Behav. Evol. 17 (1980) 452-474.] hierarchy of learning abilities
      has been revised here to better include Learning Set Formation which is
      fundamental to most forms of higher learning. This paper summarizes both the
      rationale and the methodologies that might be used to assess the roles of
      neuroanatomical structures involved in the psychological processes that serve as
      the bases of creativity.

PMID- 17434411
TI  - Creative or created: using anecdotes to investigate animal cognition.
AB  - In non-human animals, creative behaviour occurs spontaneously only at low
      frequencies, so is typically missed by standardised observational methods.
      Experimental approaches have tended to rely overly on paradigms from child
      development or adult human cognition, which may be inappropriate for species that
      inhabit very different perceptual worlds and possess quite different motor
      capacities than humans. The analysis of anecdotes offers a solution to this
      impasse, provided certain conditions are met. To be reliable, anecdotes must be
      recorded immediately after observation, and only the records of scientists
      experienced with the species and the individuals concerned should be used. Even
      then, interpretation of a single record is always ambiguous, and analysis is
      feasible only when collation of multiple records shows that a behaviour pattern
      occurs repeatedly under similar circumstances. This approach has been used
      successfully to study a number of creative capacities of animals: the
      distribution, nature and neural correlates of deception across the primate order;
      the occurrence of teaching in animals; and the neural correlates of several
      aptitudes--in birds, foraging innovation, and in primates, innovation, social
      learning and tool-use. Drawing on these approaches, we describe the use of this
      method to investigate a new problem, the cognition of the African elephant, a
      species whose sheer size and evolutionary distance from humans renders the
      conventional methods of comparative psychology of little use. The aim is both to
      chart the creative cognitive capacities of this species, and to devise
      appropriate experimental methods to confirm and extend previous findings.

PMID- 17434412
TI  - Who's afraid of a cognitive neuroscience of creativity?
AB  - This article has two goals. First, the ideas outlined here can be seen as a
      sustained and disciplined demolition project aimed at sanitizing our bad habits
      of thinking about creativity. Apart from the enormous amount of fluff out there,
      the study of creativity is, quite unfortunately, still dominated by a number of
      rather dated ideas that are either so simplistic that nothing good can possibly
      come out of them or, given what we know about the brain, factually mistaken. As
      cognitive neuroscience is making more serious contact with the knowledge base of
      creativity, we must, from the outset, clear the ground of these pernicious fossil
      traces from a bygone era. The best neuroimaging techniques help little if we
      don't know what to look for. Second, as an antidote to these theoretical duds,
      the article offers fresh ideas on possible mechanisms of creativity. Given that
      they are grounded in current understanding of cognitive and neural processes, it
      is hoped that these ideas represent steps broadly pointing in the right
      direction. In the end, the fundamental question we must ask ourselves is what,
      exactly, are the mental processes--or their critical elements--that yield
      creative thoughts.

PMID- 17434413
TI  - Creative cognition as a window on creativity.
AB  - The creative cognition approach views creativity as the generation of novel and
      appropriate products through the application of basic cognitive processes to
      existing knowledge structures. It relies on converging evidence from anecdotal
      accounts of creativity and tightly controlled laboratory studies designed to
      examine the processes that are assumed to operate in those anecdotes. Specific
      examples of creative cognition studies are described in detail with a particular
      focus on research concerned with accessing conceptual information at varying
      levels of abstraction and combining previously separate concepts. Important
      aspects of the design of these studies are delineated, including the main
      creative tasks, properties of the materials used, characteristics of responses
      observed, including their originality and practicality, participant and rater
      attributes, and the relations among these and other study aspects. Other issues
      addressed are generality across materials, populations, and situations, as well
      as causal versus correlational connections among processes, structures and
      creative outcomes.

PMID- 17434414
TI  - Creative cognition: the diverse operations and the prospect of applying a
      cognitive neuroscience perspective.
AB  - Creativity is defined quite simply as "the ability to create" in most lexicons,
      but, in reality, this is a complex and heterogeneous construct about which there
      is much to be discovered. The cognitive approach to investigating creativity
      recognizes and seeks to understand this complexity by investigating the component
      processes involved in creative thinking. The cognitive neuroscience approach,
      which has only limitedly been applied in the study of creativity, should ideally
      build on these ideas in uncovering the neural substrates of these processes.
      Following an introduction into the early experimental ideas and the cognitive
      approach to creativity, we discuss the theoretical background and behavioral
      methods for testing various processes of creative cognition, including conceptual
      expansion, the constraining influence of examples, creative imagery and insight.
      The complex relations between the underlying component processes of originality
      and relevance across these tasks are presented thereafter. We then outline how
      some of these conceptual distinctions can be evaluated by neuroscientific
      evidence and elaborate on the neuropsychological approach in the study of
      creativity. Given the current state of affairs, our recommendation is that
      despite methodological difficulties that are associated with investigating
      creativity, adopting the cognitive neuroscience perspective is a highly promising
      framework for validating and expanding on the critical issues that have been
      raised in this paper.

PMID- 17434415
TI  - How to investigate insight: a proposal.
AB  - One of the most challenging issues in the field of creativity is finding an
      approach conducent to understanding the cognitive and neural mechanisms
      underlying insight. We propose investigating the process of insight within the
      context of implicit learning paradigms. The training tasks in implicit learning
      paradigms are regularly constructed and, although participants are not informed
      about the existence of such a regularity, some of them gain insight into this
      regular pattern during training. This process of spontaneously arising explicit
      knowledge during an incidental learning situation strongly resembles the process
      of finding the solution for an insight problem. The main advantage of these
      incidental learning situations is the opportunity to investigate the process of
      insight on a trial-by-trial basis. This would be of particularly interest to
      researchers who want to relate the process of insight to neural activity. We
      begin with a description of our main findings concerning the emergence of
      explicit knowledge in implicit learning and continue with detailed descriptions
      of our implicit learning paradigm and data-analytic strategies.

PMID- 17434416
TI  - Methodologies for examining problem solving success and failure.
AB  - When designing research to examine the variables underlying creative thinking and
      problem solving success, one must not only consider (a) the demands of the task
      being performed, but (b) the characteristics of the individual performing the
      task and (c) the constraints of the skill execution environment. In the current
      paper we describe methodologies that allow one to effectively study creative
      thinking by capturing interactions among the individual, task, and problem
      solving situation. In doing so, we demonstrate that the relation between
      executive functioning and problem solving success is not always as
      straightforward as one might initially believe.

PMID- 17434417
TI  - Creativity meets neuroscience: experimental tasks for the neuroscientific study
      of creative thinking.
AB  - The psychometric assessment of different facets of creative abilities as well as
      the availability of experimental tasks for the neuroscientific study of creative
      thinking has replaced the view of creativity as an unsearchable trait. In this
      article we provide a brief overview of contemporary methodologies used for the
      operationalization of creative thinking in a neuroscientific context. Empirical
      studies are reported which measured brain activity (by means of EEG, fMRI, NIRS
      or PET) during the performance of different experimental tasks. These tasks,
      along with creative idea generation tasks used in our laboratory, constitute
      useful tools in uncovering possible brain correlates of creative thinking.
      Nevertheless, much more work is needed in order to establish reliable and valid
      measures of creative thinking, in particular measures of novelty or originality
      of creative insights.

PMID- 17434419
TI  - Methods for investigating the neural components of insight.
AB  - The authors describe how they have used visual-hemifield and event-related
      neuroimaging approaches to study their theory specifying some of the neural
      components of insight. A set of problems developed by the authors, and the use of
      solvers' self reports of insight, are presented to argue that advances in our
      understanding of insight are being unnecessarily stifled by over reliance on
      traditional insight problems and a widespread failure to determine whether
      insight has occurred on a solution-by-solution basis.

PMID- 17434418
TI  - Studying insight problem solving with neuroscientific methods.
AB  - Insights are sporadic, unpredictable, short-lived moments of exceptional thinking
      where unwarranted assumptions need to be discarded before solutions to problems
      can be obtained. Insight requires a restructuring of the problem situation that
      is relatively rare and hard to elicit in the laboratory. One way of dealing with
      this problem is to catalyze such restructuring processes using solution hints.
      This allows one to obtain multiple insight events and their accurate onset times,
      which are required for event-related designs in functional magnetic resonance
      imaging (fMRI) and Electroencephalogram (EEG), and to reliably record the
      activity associated with the restructuring component of insight. In this article,
      we discuss in detail the methodological challenges that brain research on insight
      poses and describe how we dealt with these challenges in our recent studies on
      insight problem solving.

PMID- 17434420
TI  - Current methodology and methods in psychophysiological studies of creative
      thinking.
AB  - Important points on methodology and detailed description of methods used in
      polymodal psychophysiological studies of human verbal creative thinking are
      presented. The psychophysiological studies were conducted with healthy volunteers
      during implementations of specially developed and adapted psychological tests
      aimed to bring the subjects into states of verbal creative thinking. Four
      different task sets ("story composition", "associative chains", "original
      definitions", "proverb sense flipping") were developed and applied. Positron
      emission tomography of regional cerebral blood flow (rCBF) and state-related
      quantitative electroencephalography (power and coherence evaluated) were used.
      The effectiveness of the methods is illustrated with figures.

PMID- 17434421
TI  - Cognitive neuroscience of creativity: EEG based approaches.
AB  - Cognitive neuroscience of creativity has been extensively studied using non
      invasive electrical recordings from the scalp called electroencephalograms (EEGs)
      and event related potentials (ERPs). The paper discusses major aspects of
      performing research using EEG/ERP based experiments including the recording of
      the signals, removing noise, estimating ERP signals, and signal analysis for
      better understanding of the neural correlates of processes involved in
      creativity. Important factors to be kept in mind to record clean EEG signal in
      creativity research are discussed. The recorded EEG signal can be corrupted by
      various sources of noise and methodologies to handle the presence of unwanted
      artifacts and filtering noise are presented followed by methods to estimate ERPs
      from the EEG signals from multiple trials. The EEG and ERP signals are further
      analyzed using various techniques including spectral analysis, coherence
      analysis, and non-linear signal analysis. These analysis techniques provide a way
      to understand the spatial activations and temporal development of large scale
      electrical activity in the brain during creative tasks. The use of this
      methodology will further enhance our understanding the processes neural and
      cognitive processes involved in creativity.

PMID- 17434422
TI  - Functional near-infrared spectroscopy for human brain mapping of taste-related
      cognitive functions.
AB  - Humans use various higher cognitive processes for taste, including memorization,
      recollection, and imagination, in our dietary lives, as well as in more
      specialized situations, such as sensory evaluation used in the food industry. So
      far, the cognitive aspects of taste processing have been studied mainly with
      psychological approaches, and their neural bases are not yet well understood.
      Conventional neuroimaging techniques are being used to converge psychological
      findings with human brain functions. However, these techniques require subjects
      to be in a supine position and strictly restrict head movements, narrowing the
      range of experimental paradigms that can be performed. This is especially true
      for taste studies; it is difficult to taste samples and perform cognitive tasks
      on them under conventional neuroimaging conditions. Therefore, we have attempted
      to use functional near infrared spectroscopy (fNIRS), an emerging noninvasive
      neuroimaging technique, to study human cortical taste cognitive processing.
      fNIRS, utilizing light to measure cortical hemoglobin concentration changes
      associated with neural activities, is more tolerant of subject body movement,
      thus allowing a wider range of experimental tasks for taste. However, it has some
      shortcomings that needed to be addressed. In this review, we will show how these
      technical obstacles have been overcome, how fNIRS contributes to the mapping of
      taste-related brain functions, and further promote the understanding of human
      taste processing. We propose fNIRS as a potential mediator between psychology and
      neuroscience.

PMID- 17434423
TI  - Neurite outgrowths of neurons with neurotrophin-coated carbon nanotubes.
AB  - Multiwalled carbon nanotubes (CNTs) coated with neurotrophin were used to
      regulate the differentiation and survival of neurons. Neurotrophin (nerve growth
      factor [NGF] or brain-derived neurotrophic factor [BDNF]) was covalently bound to
      CNTs modified by amino groups using a 1-ethyl-3-(3-dimethylaminopropyl)
      carbodiimide hydrochloride (EDC) reagent. The CNTs coated with NGF or BDNF
      promoted the neurite outgrowths of neurons in the same manner as soluble NGF and
      soluble BDNF. By enzyme-linked immunosorbent assay (ELISA), we demonstrated that
      neurotrophin-coated CNTs carry neurotrophin. These results suggest that
      neurotrophin-coated CNTs have biological activity and stimulate the neurite
      outgrowths of neurons.

PMID- 17434424
TI  - Characterization of prolyl oligopeptidase from hyperthermophilic archaeon
      Thermococcus sp. NA1.
AB  - The prolyl oligopeptidase TNA1_POP was found to be encoded in the genome of the
      hyperthermophilic archaeon Thermococcus sp. NA1 and showed high similarities to
      its archaeal homologs (76-83%). The enzyme was found to be a single polypeptide
      composed of 616 amino acids with conserved signature domains. A recombinant
      TNA1_POP expressed in Escherichia coli was capable of hydrolyzing succinyl-Ala
      Pro-p-nitroanilide (Suc-Ala-Pro-pNA) with temperature and pH optimums of 80
      degrees C and 7, respectively. TNA1_POP activity appeared to be significantly
      activated by pre-incubation at 80 degrees C and 90 degrees C with the optimum
      temperature unchanged. The heat-activated enzyme exhibited a k(cat) approximately
      twofold higher than that of the unheated enzyme, however, both enzymes showed the
      same K(m). TNA1_POP was thermostable at 80 degrees C retaining 80% of its heat
      activated activity even after 23 h, but it lost its enzymatic activity at 90
      degrees C with a half-life of 3 h. The loss of the enzymatic activity at 90
      degrees C seemed to be caused by the autodegradation of the enzyme, not by
      thermal denaturation, as supported by circular dichroism spectropolarimetry.
      Autodegradation fragments ranging from 2 to 18 kDa were mapped by matrix-assisted
      laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry.

PMID- 17434425
TI  - Online estimation of assimilable nitrogen by electrical conductivity measurement
      during alcoholic fermentation in enological conditions.
AB  - The monitoring of alcoholic fermentation under enological conditions is currently
      poor due to the lack of sensors for online measurements. Such monitoring is
      currently limited to the measurement of CO(2) production or changes in density.
      In this study, we determined the potential value of measuring electrical
      conductivity. We showed that this measurement is related to the assimilation of
      nitrogen, which is typically the limiting nutrient, and directly correlated to
      ammoniacal nitrogen assimilation at any percentage of ammoniacal nitrogen in the
      medium. We also used electrical conductivity for the very precise monitoring of
      the kinetics of nitrogen assimilation after the addition of a pulse of diammonium
      hydrogen phosphate (DAP) during fermentation. The impact of initial conditions
      (e.g., must composition, grape variety, pH) remains unclear, but the robustness,
      precision and low price of the sensor used justify further studies of the
      potential value of measuring electrical conductivity on the pilot and industrial
      scales.

PMID- 17434426
TI  - Hydrogen production by fermentation using acetic acid and lactic acid.
AB  - Microbial hydrogen production from sho-chu post-distillation slurry solution
      (slurry solution) containing large amounts of organic acids was investigated. The
      highest hydrogen producer, Clostridium diolis JPCC H-3, was isolated from natural
      environment and produced hydrogen at 6.03+/-0.15 ml from 5 ml slurry solution in
      30 h. Interestingly, the concentration of acetic acid and lactic acid in the
      slurry solution decreased during hydrogen production. The substrates for hydrogen
      production by C. diolis JPCC H-3, in particular organic acids, were investigated
      in an artificial medium. No hydrogen was produced from acetic acid, propionic
      acid, succinic acid, or citric acid on their own. Hydrogen and butyric acid were
      produced from a mixture of acetic acid and lactic acid, showing that C. diolis.
      JPCC H-3 could produce hydrogen from acetic acid and lactic acid. Furthermore,
      calculation of the Gibbs free energy strongly suggests that this reaction would
      proceed. In this paper, we describe for the first time microbial hydrogen
      production from acetic acid and lactic acid by fermentation.

PMID- 17434427
TI  - Direct DNA isolation from solid biological sources without pretreatments with
      proteinase-K and/or homogenization through automated DNA extraction.
AB  - Genomic DNA from solid biomaterials was directly isolated with an automated DNA
      extractor, which was based on magnetic bead technology with a bore-mediated
      grinding (BMG) system. The movement of the bore broke down the solid
      biomaterials, mixed crude lysates thoroughly with reagents to isolate the DNA,
      and carried the beads to the next step. The BMG system was suitable for the
      mechanical homogenization of the solid biomaterials and valid as an automated
      system for purifying the DNA from the solid biomaterials without the need for
      pretreatment or disruption procedures prior to the application of the solid
      biomaterials.

PMID- 17434428
TI  - Cytochrome c-552 from gram-negative alkaliphilic Pseudomonas alcaliphila AL15-21T
      alters the redox properties at high pH.
AB  - A soluble class I cytochrome c of an alkaliphile was purified and characterized,
      and its primary structure was determined. This is the first example of a soluble
      class I cytochrome c in alkaliphiles. Cells the alkaliphilic gram-negative
      bacterium Pseudomonas alcaliphila AL15-21(T) grown at pH 10 had a soluble
      cytochrome c content that was more than twofold that of strain AL15-21(T) cells
      grown at pH 7 under air-limited conditions. Cytochrome c-552, a soluble
      cytochrome c with a low molecular weight, was purified from strain AL15-21(T)
      cells grown at pH 10 under air-limited conditions. Cytochrome c-552 had a
      molecular mass of 7.5 kDa and exhibited an almost fully reduced state in the
      resting form, which exhibited absorption maxima at wavelengths of 552, 523 and
      417 nm. In the oxidized state, it exhibited an absorption maximum at 412 nm when
      it was oxidized by ferricyanide, its isoelectric point (pI) was 4.3 and it
      contained one heme c as a prosthetic group. Cytochrome c-552 was autoreduced at
      pH 10, and the autoreduction was reproducible. On the other hand, the
      autoreduction of cytochrome c-552 was not observed at pH 7.0. When pH was
      increased from 7.0 to 8.3, its midpoint redox potentials (E(m) values) increased
      from +228 mV to +276 mV as determined by redox titrations, and from +217 mV to
      +275 mV as determined by cyclic voltammetric measurements. The amino acid
      sequence deduced by cytochrome c-552 gene analysis revealed that the sequence
      consists of 96 residues, including 19 residues as an amino-terminal signal
      peptide. A phylogenetic tree based on amino acid sequence indicated that the
      protein belongs to group 4, cytochrome c(5) in class I cytochrome c.

PMID- 17434429
TI  - Effect of amplification of desensitized purF and prs on inosine accumulation in
      Escherichia coli.
AB  - The effect of a phosphoribosylpyrophosphate (PRPP) synthetase gene (prs) that was
      desensitized to feedback inhibition by ADP on inosine accumulation was
      investigated using an inosine-producing mutant of Escherichia coli. At the same
      time, various types of plasmid having a PRPP amidotransferase gene (purF) that
      was desensitized to feedback inhibition by AMP and GMP were also investigated to
      improve inosine productivity using a compatible plasmid containing prs with a
      plasmid containing purF. The recombinant E. coli I-9 harboring a low-copy-number
      plasmid having the desensitized-purF (pMWKQ) accumulated 3.6 g/l inosine from 40
      g/l glucose in a 2-d culture. Furthermore, desensitized-prs amplification, in
      addition to purF, resulted in the accumulation of 6.2 g/l inosine. Additionally,
      through these experiments, a spontaneous mutant with an enhanced inosine
      producing ability compared with the parent strain I-9 was obtained. The
      spontaneous mutant I-9m harboring only pMWKQ and I-9m harboring both pMWKQ and
      pSTVDA (a plasmid having the desensitized-prs) accumulated 6.7 g/l and 7.5 g/l
      inosine, respectively, from 40 g/l glucose in a 3-d culture.

PMID- 17434430
TI  - Innovative metabolic pathway design for efficient l-glutamate production by
      suppressing CO2 emission.
AB  - In the pathway of L-glutamic acid (L-Glu) biosynthesis in Corynebacterium
      glutamicum, 1 mol of L-Glu is synthesized from 1 mol of glucose at a cost of 1
      mol of carbon dioxide (CO(2)), with a maximum theoretical yield of 81.7% by
      weight. We have designed an innovative pathway for efficient L-Glu production
      employing phosphoketolase (PKT) to bypass the CO(2)-releasing pyruvate
      dehydrogenase reaction, thereby increasing the maximum theoretical yield of L-Glu
      from glucose to up to 98.0% by weight (120% mol/mol L-Glu produced/glucose
      consumed). The xfp gene encoding PKT was cloned from Bifidobacterium animalis and
      overexpressed under the strong cspB promoter in C. glutamicum. A functional
      enzyme was detected in an L-Glu-producing strain of C. glutamicum (odhA). When
      cells of this producer strain with the xfp gene and those without the xfp gene
      were cultivated in a controlled fermentation system, the L-Glu production yield
      of the strain expressing the xfp gene was much higher than that of the original
      strain, coupled with the suppression of CO(2) emission. Consequently, we could
      successfully enhance L-glutamate production by installing the PKT pathway of B.
      animalis into C. glutamicuml-Glu metabolism, and this novel metabolic design will
      be able to increase L-Glu production yield beyond the maximum theoretical yield
      obtained from the conventional metabolic pathway of biosynthesis from glucose.

PMID- 17434431
TI  - Determination of potent antisense oligonucleotides in vitro by semiempirical
      rules.
AB  - The selection of effective antisense target sites on a given mRNA molecule is a
      major problem in the detection of target mRNA in oligonucleotide arrays. In
      general, antisense oligodeoxynucleotides (asODNs) of about 10-20 nucleotides (nt)
      in length are used. However, the demand for predicting the sequence of potent
      asODNs much longer than those mentioned above has been increasing. Here, we
      prepared 40-nt asODNs directed against fluorescence-labeled green fluorescent
      protein (GFP) mRNA and quantified their hybridization efficiencies by
      fluorescence microscopy. We found that the hybridization efficiency depended on
      the TC content or the minimum free energy of the asODNs. On the basis of these
      findings, a semiempirical parameter called accessibility score was introduced to
      predict the potency of asODNs. The results of this study aided in the development
      of an effective two-step procedure for determining mRNA accessibility, namely,
      the computer-aided selection of asODN binding sites using an accessibility score
      followed by an experimental procedure for measuring the hybridization
      efficiencies between the selected asODNs and the target mRNA by fluorescence
      microscopy.

PMID- 17434432
TI  - Effects of inner-phase components of water-in-oil-in-water emulsion on low-pH
      tolerance of Lactobacillus acidophilus incorporated into inner-water phase.
AB  - The incorporation of Lactobacillus acidophilus, which has a low acid tolerance,
      into the inner-water phase of water-in-oil-in-water (W/O/W) emulsion improved the
      bacterial survival rate in a model gastric juice. The components that enhanced
      the acid tolerance of the bacterium in W/O/W emulsion were investigated. Although
      the acid tolerance enhancement induced by the tested components was low at pH 2,
      some components significantly improved the tolerance at pH 4. In particular, the
      acid tolerance enhancement induced by yeast extract and sodium caseinate was
      marked.

PMID- 17434433
TI  - Efficient conversion of allitol to D-psicose by Bacillus pallidus Y25.
AB  - An efficient method for conversion of allitol to D-psicose was achieved by a
      resting cell reaction of Bacillus pallidus Y25 for the first time. Notably, it
      was possible to produce D-allose and D-altrose from allitol directly via D
      psicose by prolonging the reaction time. This method was applied for the
      preparation of D-psicose using the extract of Itea virginica as a starting
      material in this study. D-Psicose which is the absolutely key precursor for the
      production of other six carbon sugars could be obtained as the sole product at
      high yield.

PMID- 17434434
TI  - Picture recognition without picture identification: a method for assessing the
      role of perceptual information in familiarity-based picture recognition.
AB  - The present study examined the claim that unidentifiable test-pictures are
      processed and recognized on a perceptual, as opposed to a conceptual, level.
      Using an extension of the recognition without identification paradigm (e.g.,
      Cleary, A. M. & Greene, R. L. (2000). Recognition without identification. Journal
      of Experimental Psychology: Learning, Memory, and Cognition, 26, 1063-1069;
      Peynircioglu, Z. F. (1990). A feeling-of-recognition without identification.
      Journal of Memory and Language, 29, 493-500), it was observed that when test
      pictures were unidentifiable during a masked perceptual identification task, old
      new discrimination occurred when the study-list consisted of pictures
      (Experiments 1-3), but not when the study-list consisted of picture names
      (Experiment 2) or when picture exemplars served as test-cues (Experiment 3).
      Results provide converging evidence that a study-test perceptual match is needed
      for the episodic recognition of unidentified test-pictures. Implications for the
      present paradigm as a tool for examining the role of perceptual information in
      recognition-familiarity are discussed.

PMID- 17434435
TI  - Deep anterior lamellar keratoplasty by big-bubble technique for treatment corneal
      stromal opacities.
AB  - PURPOSE: To evaluate the efficacy of using the big-bubble technique of deep
      anterior lamellar keratoplasty (DALK) for newer indications. DESIGN: Prospective,
      noncomparative, interventional case series. METHODS: Ten eyes of eight patients
      with pathologies involving the corneal stroma and sparing the Descemet membrane
      (DM) were included in this study conducted at a tertiary care hospital. The
      indications for DALK included corneal clouding attributable to
      mucopolysaccharidoses (n = 2), macular corneal dystrophy (n = 5), lattice corneal
      dystrophy (n = 1), granular corneal dystrophy (n = 1), and stromal scar
      attributable to infectious keratitis (n = 1). DALK was performed using the big
      bubble technique in order to achieve the complete separation of DM from the
      corneal stromal tissue in the recipient's eye. Subsequently, the corneal stromal
      tissue was excised completely, and a full-thickness donor corneal lenticule
      without its DM was secured over the bared DM of the host. The main outcome
      measures of the study were the ability to successfully bare DM, the gain in
      visual acuity, and the presence of any complications. RESULTS: Using the big
      bubble technique, DM was bared, and DALK could be performed successfully in all
      eyes. No intraoperative or postoperative complications were observed. All
      patients achieved a best-corrected visual acuity (BCVA) of 20/40 or better at the
      end of six months. CONCLUSIONS: DALK using the big-bubble technique can be useful
      in treating corneal stromal dystrophies, corneal clouding attributable to
      mucopolysaccharidoses, and stromal scar attributable to infectious keratitis.

PMID- 17434436
TI  - Multifocal posterior necrotizing retinitis.
AB  - PURPOSE: To describe the clinical features of an acute, inflammatory, and
      progressive retinal necrosis that affects primarily the posterior pole. DESIGN:
      Retrospective, interventional case series. METHODS: Twenty-seven eyes of 24
      patients diagnosed with and treated for acute retinal necrosis (ARN) were
      categorized into two groups according to the predominant location of retinitis at
      presentation: either in the peripheral retina or in the posterior pole. Clinical
      features, disease progression, visual outcomes, and complications of these two
      groups were compared. RESULTS: Fifteen eyes demonstrated the known peripheral
      retinitis pattern, and 12 eyes exhibited a pattern of retinitis that affected
      mainly the posterior pole. Eyes with peripheral retinitis showed focal, well
      demarcated areas of retinal necrosis in the periphery with rapid circumferential
      progression and rare involvement of the posterior pole. All eyes with posterior
      pole retinitis had multifocal deep lesions posterior to the vortex veins at
      presentation, and half of these eyes had lesions in the macula. These lesions
      progressed to patches of confluent retinitis in both the periphery and the
      posterior pole. There was no significant difference between the two groups in the
      incidence of anterior chamber and vitreous cells, vascular sheathing, retinal
      hemorrhages, or optic disk edema. Patients with posterior retinitis involvement
      seemed to have a worse visual outcome during the first two years after diagnosis.
      The Cox proportional hazards model suggested a higher incidence of retinal
      detachment in patients with posterior retinitis (P = .07). CONCLUSIONS: The
      authors report a pattern of herpetic retinitis that affects predominantly the
      posterior pole and may have a worse visual prognosis and a higher rate of retinal
      detachment.

PMID- 17434439
TI  - [Who am I: I...?].

PMID- 17434437
TI  - Surveillance of the eye and vision in clinical trials of CP-675,206 for
      metastatic melanoma.
AB  - PURPOSE: To determine the ocular safety of CP-675,206 (Pfizer, New York, New
      York, USA), a fully human anti-cytotoxic T lymphocyte-associated antigen 4
      monoclonal antibody in clinical trials of immunotherapy of metastatic melanoma.
      DESIGN: Prospective, nonrandomized study of the eye and vision in phase I/II
      clinical trials of CP-675,206 in metastatic melanoma conducted at the University
      of California, Los Angeles. METHODS: Patients with regional or distant metastatic
      melanoma were enrolled in phase I/II clinical trials evaluating the safety and
      antitumor efficacy of CP-675,206 alone or in combination with melanoma antigen
      peptide-pulsed dendritic cell vaccines. Ophthalmic evaluation was performed at
      the onset of CP-675,206 immunotherapy (baseline evaluation), two months or more
      after the onset of CP-675,206 immunotherapy (end-study evaluation), and at two-
      to three-month intervals thereafter in patients who continued to receive CP
      675,206 immunotherapy (poststudy evaluation). Baseline and end-study evaluations
      included comprehensive ophthalmic examination, psychophysical and
      electrophysiologic visual function assessment, fundus photography, fluorescein
      angiography, and visual function assessment. RESULTS: Twenty patients with
      metastatic melanoma arising from the skin, mucosa, eye, or unknown site were
      evaluated. Systemic toxicity attributed to CP-675,206 included dermatologic
      manifestations, diarrhea, and autoimmune hepatitis with panhypopituitarism. A
      subset of patients receiving CP-675,206 demonstrated antitumor efficacy with
      partial response or complete response of metastatic melanoma. Comparison of
      ophthalmic baseline with end-study evaluations in all 20 patients and limited
      term poststudy evaluations showed no adverse effect of CP-675,206 immunotherapy
      on the eye or vision. CONCLUSIONS: In this study, CP-675,206 immunotherapy for
      metastatic melanoma did not adversely affect the eye or vision.

PMID- 17434438
TI  - Fast, convenient, and economical method for isolating genomic DNA from lactic
      acid bacteria using a modification of the protein "salting-out" procedure.

PMID- 17434440
TI  - Effects of working conditions and sleep of the previous day on cognitive
      performance.
AB  - The study examined the consequences of working conditions on the previous day on
      cognitive performance the following day. It also addressed the issue of whether
      this relationship was mediated by sleep and whether it differed as a function of
      age. The data were taken from the VISAT study (aging, health and work) and
      concerned the participant's general work schedule, general sleep quality, working
      conditions on the previous day (content, duration, load and schedule), subsequent
      sleep length and quality, and cognitive performance. Results showed that both
      physical activity and working before 6 am or after 10 pm on the previous day were
      significantly associated with poorer cognitive performance. Significant effects
      of working conditions on the previous day were also observed on subsequent sleep,
      but these effects did not mediate the relationship between working conditions and
      cognitive performance. The observed effect on cognitive performance of atypical
      work hours on the previous day was similar for all ages, probably because of the
      healthy worker effect.

PMID- 17434441
TI  - Chemical rescue of a site-modified ligand to a [4Fe-4S] cluster in PsaC, a
      bacterial-like dicluster ferredoxin bound to Photosystem I.
AB  - Chemical rescue of site-modified amino acids using externally supplied organic
      molecules represents a powerful method to investigate structure-function
      relationships in proteins. Here we provide definitive evidence that aryl and
      alkyl thiolates, reagents typically used for in vitro iron-sulfur cluster
      reconstitutions, serve as rescue ligands to a site-specifically modified [4Fe
      4S](1+,2+) cluster in PsaC, a bacterial dicluster ferredoxin-like subunit of
      Photosystem I. PsaC binds two low-potential [4Fe-4S](1+,2+) clusters termed F(A)
      and F(B). In the C13G/C33S variant of PsaC, glycine has replaced cysteine at
      position 13 creating a protein that is missing one of the ligating amino acids to
      iron-sulfur cluster F(B). Using a variety of analytical techniques, including non
      heme iron and acid-labile sulfur assays, and EPR, resonance Raman, and Mossbauer
      spectroscopies, we showed that the C13G/C33S variant of PsaC binds two [4Fe
      4S](1+,2+) clusters, despite the absence of one of the biological ligands. (19)F
      NMR spectroscopy indicated that the external thiolate replaces cysteine 13 as a
      substitute ligand to the F(B) cluster. The finding that site-modified [4Fe
      4S](1+,2+) clusters can be chemically rescued with external thiolates opens new
      opportunities for modulating their properties in proteins. In particular, it
      provides a mechanism to attach an additional electron transfer cofactor to the
      protein via a bound, external ligand.

PMID- 17434442
TI  - Accommodation of NO in the active site of mammalian and bacterial cytochrome c
      oxidase aa3.
AB  - Following different reports on the stoichiometry and configuration of NO binding
      to mammalian and bacterial reduced cytochrome c oxidase aa(3) (CcO), we
      investigated NO binding and dynamics in the active site of beef heart CcO as a
      function of NO concentration, using ultrafast transient absorption and EPR
      spectroscopy. We find that in the physiological range only one NO molecule binds
      to heme a(3), and time-resolved experiments indicate that even transient binding
      to Cu(B) does not occur. Only at very high (approximately 2 mM) concentrations a
      second NO is accommodated in the active site, although in a different
      configuration than previously observed for CcO from Paracoccus denitrificans [E.
      Pilet, W. Nitschke, F. Rappaport, T. Soulimane, J.-C. Lambry, U. Liebl and M.H.
      Vos. Biochemistry 43 (2004) 14118-14127], where we proposed that a second NO does
      bind to Cu(B). In addition, in the bacterial enzyme two NO molecules can bind
      already at NO concentrations of approximately 1 microM. The unexpected
      differences highlighted in this study may relate to differences in the
      physiological relevance of the CcO-NO interactions in both species.

PMID- 17434443
TI  - Structure of the C-terminal domain of the pro-apoptotic protein Hrk and its
      interaction with model membranes.
AB  - The protein harakiri (Hrk) is a pro-apoptotic BH3-only protein which belongs to
      the Bcl-2 family. Hrk appears associated to the mitochondrial outer membrane,
      apparently by a putative transmembrane domain, where it exerts its function. In
      this work we have identified a 27mer peptide supposed to be the putative membrane
      domain of the protein at the C-terminal region, and used infrared and
      fluorescence spectroscopies to study its secondary structure as well as to
      characterize its effect on the physical properties of phospholipid model
      membranes. The results presented here showed that the C-terminal region of Hrk
      adopts a predominantly alpha-helical structure whose proportion and
      destabilization capability varied depending on phospholipid composition. Moreover
      it was found that the orientation of the alpha-helical component of this C
      terminal Hrk peptide was nearly perpendicular to the plane of the membrane. These
      results indicate that this domain is able of inserting into membranes, where it
      adopts a transmembrane alpha-helical structure as well as it considerably
      perturbs the physical properties of the membrane.

PMID- 17434444
TI  - Theory-of-mind, cognitive development, and children's interpretation of anxiety
      related physical symptoms.
AB  - The present study investigated developmental patterns in children's
      interpretation of anxiety-related physical symptoms and emotional reasoning, and
      to what extent these phenomena are influenced by children's level of cognitive
      development. A large sample of 4-13-year-old children (N=358) were exposed to
      vignettes in which the presence and absence of physical symptoms was
      systematically varied. In addition, children completed a series of conservation
      tasks and a theory-of-mind-test. Results demonstrated that from the age of 7,
      children were increasingly able to link physical symptoms to anxiety.
      Furthermore, cognitive development appeared to enhance children's ability to
      interpret physical symptoms as a sign of anxiety. Further, children's tendency to
      infer danger from vignettes with physical symptoms (i.e., emotional reasoning)
      was already prominent in 4-6-year-olds. The implications for physical symptom
      based theories of childhood anxiety are briefly discussed.

PMID- 17434446
TI  - N-Acetylgalactosaminyltransferase 14, a novel insulin-like growth factor binding
      protein-3 binding partner.
AB  - Insulin-like growth factor binding protein-3 (IGFBP-3) is known to inhibit cell
      proliferation and induce apoptosis in IGF-dependent and IGF-independent manners,
      but the mechanism underlying IGF-independent effects is not yet clear. In a yeast
      two-hybrid assay, IGFBP-3 was used as the bait to screen a human fetal liver cDNA
      library for it interactors that may potentially mediate IGFBP-3-regulated
      functions. N-Acetylgalactosaminyltransferase 14 (GalNAc-T14), a member of the
      GalNAc-Tases family, was identified as a novel IGFBP-3 binding partner. This
      interaction involved the ricin-type beta-trefoil domain of GalNAc-T14. The
      interaction between IGFBP-3 and GalNAc-T14 was reconfirmed in vitro and in vivo,
      using GST pull-down, co-immunoprecipitation and mammalian two-hybrid assays. Our
      findings may provide new clues for further study on the mechanism behind the IGF
      independent effects of IGFBP-3 promoting apoptosis. The role of GalNAc-T14 as an
      intracellular mediator of the effects of IGFBP-3 need to be verified in future
      studies.

PMID- 17434445
TI  - The mitochondrial tRNA(Ala) T5628C variant may have a modifying role in the
      phenotypic manifestation of the 12S rRNA C1494T mutation in a large Chinese
      family with hearing loss.
AB  - We report here the clinical, genetic, and molecular characterization of a large
      Han Chinese family with aminoglycoside-induced and nonsyndromic hearing loss. Two
      and 13 of 66 matrilineal relatives suffered from aminoglycoside-induced and
      nonsyndromic hearing loss, respectively. These matrilineal relatives exhibited a
      wide range of severity of hearing loss, varying from profound to normal hearing.
      In the absence of aminoglycosides, the age-at-onset of hearing impairment in
      these matrilineal relatives ranged from 13 to 50years. Furthermore, these
      affected matrilineal relatives shared some common features: bilateral hearing
      loss of high frequencies and symmetries. Sequence analysis of mitochondrial DNA
      (mtDNA) in the pedigree identified the homoplasmic 12S rRNA C1494T mutation and
      other 34 variants belonging to Eastern Asian haplogroup F1. Of these, the variant
      T5628C occurs at an extremely conserved nucleotide (A31) of tRNA(Ala). This
      variant converted a very conservative A-U to a G-U base-pairing at AC-stem of
      this tRNA. The disruption of this base-pairing in tRNAs by mtDNA mutations has
      been associated with several clinical abnormalities. The alteration of structure
      of the tRNA(Ala) by the T5628C mutation may lead to a failure in tRNA metabolism
      and lead to impairment of mitochondrial translation, thereby worsening
      mitochondrial dysfunctions, caused by the C1494T mutation. Therefore, this mtDNA
      mutation may influence the phenotypic manifestation of the 12S rRNA C1494T
      mutation in this Chinese pedigree.

PMID- 17434447
TI  - Assay optimization and kinetic profile of the human and the rabbit isoforms of
      11beta-HSD1.
AB  - Assay conditions for the 11beta-hydroxysteroid dehydrogenase have been optimized
      by adding phospholipids in the media buffer to increase and stabilize the
      enzymatic activity. The presence of phospholipids greatly facilitates the study
      of the binding of cortisone and NADPH at the enzyme catalytic site. Kinetic
      analyses conducted with the human and rabbit enzyme isoforms suggest that both
      enzymes behave according to an ordered sequential bi-bi mechanism where the NADPH
      is the first to bind at the active site followed by cortisone. The equilibrium
      dissociation constant, K(i)a as well as the apparent Michaelis-Menten constants
      K(m)a, K(m)b, k(cat)a, and k(cat)b for NADPH and cortisone, have been determined
      to be 147.5 microM, 14.4 microM, 43.8 nM, 0.21 min(-1), and 0.27 min(-1),
      respectively, for the human enzyme and 41.1 microM, 3.1 microM, 161.7 nM, 0.49
      min(-1), and 0.52min(-1), respectively, for the rabbit enzyme.

PMID- 17434448
TI  - Upregulation of dentin matrix protein 1 promoter activities by core binding
      factor alpha1 in human dental pulp stem cells.
AB  - An osteoblast-specific transcription factor, core binding factor alpha1
      (Cbfalpha1), is critical for osteoblast and odontoblast differentiation. In this
      study, the role of Cbfalpha1 in human dentin matrix protein1 (DMP1) gene
      expression in human dental pulp stem cells (HDPSCs) was investigated. The desired
      promoter fragments were obtained and cloned into the pGL3-basic vector. It was
      found that Cbfalpha1 isoforms were predominantly expressed in the cytoplasm of
      the HDPSCs and reached to the maximum after transfection for 48h. Furthermore,
      forced overexpression of Cbfalpha1 induced the increase of the luciferase
      activities of pGL3-P1-6, especially those of pGL3-P(-505to+86) (p<0.05) were the
      most significant. Then the site-directed mutagenesis of Cbfalpha1 binding sites
      in the promoter region of nt -505 to +86 resulted in a marked decline of
      luciferase activities. Thus, our results suggest that Cbfalpha1 upregulates DMP1
      gene expression differentially that may contribute to the spatial-temporal
      expression pattern of DMP1 during odontoblast differentiation.

PMID- 17434449
TI  - Hypoxia-enhanced expression of free deaminoneuraminic acid in human cancer cells.
AB  - Hypoxia is a common characteristic of locally advanced tumors and cancer cells of
      high invasiveness and metastasis. We first demonstrate that hypoxic culture of
      human cancer HeLa, LS174T, and Caco-2 cells enhances the de novo synthesis of
      free sialic acids including deaminoneuraminic acid (Kdn), a unique sialic acid.
      Hypoxic cultures enhance expression of the N-acetylneuraminic acid (Neu5Ac) 9
      phosphate synthetase (NPS) and phosphomannoisomerase (PMI) mRNAs and their
      enzymatic activities. In addition, incorporation of mannose (Man) into the cells
      is also enhanced. The elevated NPS activity facilitates the synthesis of Kdn as
      well as Neu5Ac, a typical sialic acid in human. The increased PMI activity,
      together with the enhanced Man-incorporation ability, leads to the increase of
      mannose 6-phosphate, which is a substrate of NPS, and subsequently results in the
      increased expression of Kdn, but not Neu5Ac. Kdn may thus be a target for
      diagnosis of cancers.

PMID- 17434450
TI  - Activation of the SCPx promoter in mouse adrenocortical Y1 cells.
AB  - Sterol carrier protein X (SCPx) is a peroxisomal protein with both lipid transfer
      and thiolase activity. Treatment of mouse adrenal Y1 cells with cAMP for 24h
      caused a significant induction of SCPx mRNA levels. Reporter gene studies
      demonstrated that treatment with cAMP and SF-1 was able to activate the SCPx
      promoter. Sequence analysis revealed the presence of three putative steroidogenic
      factor-1 (SF-1) binding motifs (designated SFB1, SFB2, and SFB3) and one CRE.
      Only SFB1 and SFB3 were able to bind recombinant SF-1 protein in electrophoretic
      mobility shift assays. The CRE was able to form a DNA/protein complex in the
      presence of Y1 nuclear extracts. Mutational analysis studies demonstrated that
      SFB3 is required for full activation of the SCPx promoter by cAMP treatment.
      Regulation of the SCPx gene by SF-1 and cAMP is similar to the regulatory
      mechanisms observed for other steroidogenic genes.

PMID- 17434451
TI  - Intracellular siRNA delivery system using polyelectrolyte complex micelles
      prepared from VEGF siRNA-PEG conjugate and cationic fusogenic peptide.
AB  - To develop a small interfering RNA (siRNA) delivery system with low cytotoxicity
      and high transfection efficiency, siRNA was conjugated to poly(ethylene glycol)
      via a disulfide linkage (siRNA-PEG) to prepare polyelectrolyte complex micelles
      (PECMs) by condensing with a cationic fusogenic peptide (KALA). The siRNA-PEG
      conjugate exhibited enhanced resistance to degradation from nucleases. Anionic
      siRNA-PEG conjugate and cationic KALA, when mixed in an aqueous phase,
      spontaneously formed nano-sized PECMs (<200nm) that have an inner core of charge
      neutralized siRNA/KALA complex surrounded by a PEG corona. Vascular endothelial
      growth factor (VEGF) siRNA was used to demonstrate VEGF sequence-specific gene
      inhibition in prostate carcinoma cells (PC-3 cells). The extent of gene silencing
      was gradually increased with increasing nitrogen to phosphate (N/P) ratio and the
      concentration of siRNA-PEG/KALA PECMs. These results suggest that the formulation
      of siRNA-PEG/KALA PECMs could be widely applied for intracellular delivery of
      various therapeutic siRNAs.

PMID- 17434452
TI  - Molten globule state of tear lipocalin: ANS binding restores tertiary
      interactions.
AB  - Tear lipocalin (TL) may stabilize the lipid layer of tears through a molten
      globule state triggered by low pH. EPR spectroscopy with site-directed spin
      labeling, revealed the side chain mobility of residues on the G-strand of TL in a
      molten globule state; the G-strand retains beta-sheet structure. All of the side
      chains of G-strand residues become more loosely packed, especially residues 96
      99. In contrast, the highly mobile side chain of residue 95 on the F-G loop,
      becomes tightly packed. ANS binding to TL in a molten globule state reestablishes
      tight packing around side chains that are oriented both inside and outside of the
      barrel. Unlike RBP and BLG; TL has no disulfide bond between G- and H-strands. It
      is likely that the central beta-sheet in the molten globule state of lipocalins
      is stabilized by its interactions with the main alpha-helix, rather than the
      interstrand disulfide bond.

PMID- 17434453
TI  - Ectopic expression of systemic RNA interference defective protein in embryonic
      stem cells.
AB  - RNA interference (RNAi), a post-transcriptional gene silencing mechanism
      originally described in Caenorhabditis elegans, involves sequence-specific mRNA
      degradation mediated by double-stranded RNAs (dsRNAs). Passive dsRNA uptake has
      been uniquely observed in C. elegans due to the expression of systemic RNA
      interference defective-1 (SID-1). Here we investigated the ability of ectopic SID
      1 expression to enable passive cellular uptake of short interfering RNA (siRNA)
      or double stranded RNA (dsRNA) in pluripotent mouse embryonic stem cells (mESCs).
      When SID-1-GFP and the Firefly luciferase reporter gene (luc(Fir)) were co
      expressed in mESCs, luc(Fir) activity could be suppressed by simple incubation
      with dsRNAs/siRNAs that were designed to specifically target luc(Fir). By
      contrast, suppression was not observed in mESCs expressing luc(Fir) and GFP alone
      or when either GFP- or SID-1-GFP-expressing cells were incubated with control
      dsRNAs/siRNAs (non-silencing or Renilla luciferase-specific). These results may
      lead to high-throughput experimental strategies for studying ESC differentiation
      and novel approaches to genetically inhibit or eliminate the tumorigenicity of
      ESCs.

PMID- 17434454
TI  - Regulation of glutathione transferase P: a tumor marker of hepatocarcinogenesis.
AB  - Placental glutathione transferase (GST-P) is specifically expressed during rat
      haptocarcinogenesis, and has been used as a reliable tumor marker for
      experimental hepatocarcinogenesis in the rat. The regulation of this tumor marker
      gene may be associated with the process of carcinogeneisis. By elucidating the
      mechanisms of such tumor marker gene expression, we may shed light on the
      molecular mechanisms of carcinogenesis. We analyzed the regulation of the GST-P
      gene and found that the strong enhancer element GPE1 (GST-P enhancer-1)
      specifically regulates the GST-P gene by interacting with specific transcription
      factors in normal liver and during hepatocarcinogenesis. In particular,
      C/EBPalpha was required for the suppression of GST-P gene in normal liver,
      whereas the Nrf2/MafK heterodimer was required for the activation of this gene
      during hepatocarcinogenesis. In this Mini-Review, we describe the positive and
      negative regulatory mechanisms in the pre-cancerous and normal liver,
      respectively.

PMID- 17434455
TI  - Medial frontal hyperactivity in reality distortion.
AB  - BACKGROUND: Schizophrenia/schizoaffective disorder involves reality distortion
      (RD), which impairs the ability to process socioemotional information. Because
      this psychological capacity maps to the medial prefrontal cortex (MPFC) and
      schizophrenia involves abnormal MPFC function, we tested the hypothesis that
      treated schizophrenic/schizoaffective patients with persistent RD (RD+) would
      exhibit greater MPFC dysfunction than patients without significant RD (RD-). The
      amygdala interacts with MPFC, also carries out socioemotional processing, and has
      been implicated in schizophrenia; thus, we also tested the hypothesis that
      patients would exhibit aberrant amygdala activity. METHODS: Eleven RD+ patients,
      12 RD- patients, and 15 healthy control subjects (HC) viewed emotionally salient
      pictures with neutral, aversive, and positive content during the acquisition of
      blood oxygenation level-dependent (BOLD) sensitive functional magnetic resonance
      imaging. RESULTS: All groups had similar behavioral responses to the pictures.
      The RD+ subjects had greater BOLD responses (compared with the RD- and HC groups)
      to the aversive pictures in the anterior MPFC. Both patient groups showed reduced
      activation in MPFC and the left amygdala (compared with HC) for neutral pictures
      (compared with blank condition), although this effect could be explained by
      medication. CONCLUSIONS: Reality distortion is associated with hyperactivity of
      the MPFC in schizophrenic/schizoaffective patients whose symptoms persist in
      spite of antipsychotic treatment.

PMID- 17434457
TI  - Matrix metalloproteinase-9 deficiency has no effect on glial scar formation after
      transient focal cerebral ischemia in mouse.
AB  - Glial scar formation was investigated in wild-type and MMP-9 deficient mice
      during a period of 21 days after 45 min of focal cerebral ischemia by
      intraluminal thread occlusion of the middle cerebral artery. The results showed
      no differences in the kinetics of activation of microglia, oligodendrocyte
      precursors and reactive astrocytes and showed only a slight difference in the
      pattern of macrophage infiltration. These results suggest that a specific
      targeting of MMP-9, as a mean to prevent ischemia-induced blood-brain barrier
      disruption, would have no significant effects on the recruitment of cells
      involved in glial scar formation.

PMID- 17434456
TI  - Depression and inflammation in patients with coronary heart disease: findings
      from the Heart and Soul Study.
AB  - BACKGROUND: Depression and inflammation independently predict adverse
      cardiovascular outcomes in patients with coronary heart disease (CHD). Depression
      has been associated with elevated levels of inflammation in otherwise healthy
      patients without known CHD. However, studies investigating the link between
      depression and inflammation in patients with established CHD have produced
      inconclusive results. METHODS: We sought to examine the association of major
      depression with inflammation in 984 outpatients with established CHD from the
      Heart and Soul Study. We assessed current major depression with the Computerized
      Diagnostic Interview Schedule and collected venous blood samples for measurement
      of five inflammatory biomarkers (white blood cell count, CD40 ligand, C-reactive
      protein [CRP], fibrinogen, and interleukin-6 [IL-6]). We used multivariate
      analysis of variance to examine the association of current depression with
      inflammatory markers, adjusted for potential confounding variables. RESULTS: Of
      the 984 participants, 217 (22%) had current major depression. Depression was not
      associated with increased levels of any inflammatory marker. Contrary to our
      hypothesis, depression was associated with lower levels of CRP (p = .09),
      fibrinogen (p = .006), and IL-6 (p = .007) in both unadjusted and adjusted
      models. CONCLUSIONS: We found no evidence that current depression is associated
      with greater inflammation in outpatients with CHD. Inflammation is unlikely to
      explain the adverse cardiovascular outcomes associated with depression in
      patients with established CHD.

PMID- 17434458
TI  - Controlled retrieval processing in recognition memory exclusion tasks.
AB  - ERPs were acquired in the test phases of two memory tasks where three classes of
      word were presented: (i) words encountered in a study phase (studied words), (ii)
      words presented at test for the first time (new words), and (iii) new words
      repeated after a lag of 7-9 words (repeated test words). In Experiment 1,
      participants responded on one key to studied words (targets) and on a second to
      repeated test words (non-targets) as well as to new words. In Experiment 2,
      participants responded on one key to repeated test words (targets) and on a
      second key to new and studied words (non-targets). The likelihood of a correct
      response to a target was higher in Experiment 2 than in Experiment 1. In both
      experiments, the focus for the ERP analyses was on parietally distributed ERP
      old/new effects, which are assumed to index recollection. Reliable parietal
      old/new effects were obtained for targets as well as non-targets in Experiment 1,
      but for targets only in Experiment 2. This pattern of data is consistent with
      previous suggestions that, when the likelihood of recollecting information about
      targets is high, participants use the success or failure of an attempt to
      recollect information about targets as the basis for distinguishing between
      targets and all other classes of test word. The findings in these two experiments
      are informative because they: (i) generalise those obtained in previous work to a
      different exclusion paradigm, (ii) add emphasis to claims regarding the potential
      utility of this particular paradigm in studies where changes in memory control
      according to age are assessed, and (iii) highlight important considerations when
      behavioural data obtained in exclusion tasks are employed in order to make
      estimates of the relative contributions of recollection and familiarity to task
      performance.

PMID- 17434459
TI  - Transcription factor p53 in degenerating spinal cords.
AB  - The causes of spinal cord cell loss in motor neuron disorders such as amyotrophic
      lateral sclerosis (ALS) are currently unknown. A role can be postulated for the
      transcription factor p53, which can induce apoptosis via upregulation of
      proapoptotic genes (e.g., Bax) and inhibition of antiapoptotic genes (e.g., Bcl
      2). A model of motor neuron loss is the wobbler mouse that exhibits rapid motor
      neuron cell death as well as motor deficit from 21 days after birth. Affymetrix
      microarray data from wobbler mice demonstrate a 2.2-fold increase in p53 signal
      compared with their normal littermates, whereas qRT-PCR of RNA from laser capture
      microdissected ventral horns of normal and wobbler mice reveals a larger 6.6-fold
      increase in gene expression and this was supported by western blotting. Human
      ventral horns obtained from ALS and age-matched normal spinal cords also
      demonstrated an increase (2.7-fold) in p53 expression as determined by qRT-PCR.
      Evidence of a causative role for p53 in spinal cord cell death was provided by
      use of a p53 inhibitor, pifithrin-alpha, in organotypic slice cultures of mouse
      spinal cord. A 24-h pretreatment with pifithrin-alpha (and continuing in the
      presence of insult), significantly reduced the toxicity of a 48-h treatment with
      FeSO(4), tested with the MTT viability assay. These results indicate that p53
      plays a functional role in oxidative stress-induced cell death and supports the
      possibility that elevated p53 could be involved in motor neuron death in ALS and
      the wobbler mouse.

PMID- 17434460
TI  - Effects of a mutation in the TM2-TM3 linker region of the glycine receptor alpha1
      subunit on gating and allosteric modulation.
AB  - Alcohols and volatile anesthetics modulate the function of cys-loop ligand-gated
      ion channels, binding to a putative site between transmembrane domains two and
      three. The extracellular linker between these two domains is important in the
      transduction of the gating signal from the glycine binding site to the channel
      gate. Although the anesthetic binding site is proposed to be in the same region
      throughout the cys-loop receptor family, the modulatory effects of these
      compounds depend on the receptor. A sequence comparison revealed an extra proline
      in the TM2-TM3 loop of the 5-HT3A receptor (5-HT3AR) that is not found in the
      glycine receptor (GlyR). We hypothesized that this proline residue could affect
      the size and orientation of the putative alcohol and anesthetic binding pocket
      and perhaps explain some of the differences in alcohol and anesthetic effects
      seen in this family of receptors. A lysine to proline mutation was introduced
      into the TM2-TM3 linker region at position 281 (K281P) of the alpha1 GlyR.
      Mutation at this residue did not affect thiol binding to residues in TM2 or TM3
      and it does not appear that residue 281 constitutes part of the alcohol binding
      site. The K281P receptors displayed constitutive activity in the absence of
      glycine, and unlike wild-type receptors, this channel opening was antagonized by
      application of either volatile anesthetics or another GlyR modulator, zinc. Our
      data suggest that the TM2-TM3 extracellular loop plays a role in the transduction
      of signals generated by allosteric modulators in addition to gating signals that
      follow glycine binding.

PMID- 17434461
TI  - A mismatch negativity study of local-global auditory processing.
AB  - We used mismatch negativity (MMN) to examine structural encoding of local and
      global auditory patterns in perceptual memory. Unlike previous MMN studies of
      local-global auditory perceptual organization that used interval-contour stimuli,
      here we presented hierarchical stimuli in which local pattern organization formed
      global patterns. Importantly, our stimuli allowed independent manipulation of the
      two structural levels. In separate blocks, participants were exposed to frequent
      local standard patterns and rare local deviant patterns, or to frequent global
      standard patterns and rare global deviant patterns. Within each deviant pattern,
      the variation from the standard pattern could occur at onset (early), towards the
      end of the pattern (late) or over both time windows (both). To isolate pattern
      indexing at one level, the other level continuously changed (e.g., in a global
      standard block, local elements varied trial-by-trial). MMN was found only for
      global deviant patterns, and only when deviation occurred late in the pattern. In
      a separate behavioral experiment, global deviants were detected more often than
      local ones, although initial similarity followed by a late deviation from the
      standard pattern was not required for explicit deviant detection (as with the
      MMN). This report demonstrates neural structural encoding for global information,
      when independently manipulated from local information. Furthermore, it extends
      previous MMN findings that have revealed indexing of complex abstract auditory
      information to the realm of hierarchical perceptual organization.

PMID- 17434462
TI  - Akt up- and down-regulation in response to endoplasmic reticulum stress.
AB  - Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of CNS
      diseases such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia.
      In the present study, we found that Akt activation is regulated dually by ER
      stress in primary cultured glial cells. We observed that Akt activation was
      increased by short-term exposure to ER stress but was down-regulated by long-term
      exposure to ER stress. ER stress-induced Akt activation was mediated through
      phosphatidylinositol 3-kinase (PI3K) because the PI3K inhibitors, LY294002 and
      wortmannin, inhibited Akt activation. Moreover, Akt was localized in the ER, as
      assessed by immunohistochemistry, and ER stress increased microsomally localized
      Akt activation. These results suggest that Akt plays an important role in stress
      conditions, which impair ER function.

PMID- 17434463
TI  - A functional in vitro model of rat blood-brain barrier for molecular analysis of
      efflux transporters.
AB  - Physiological studies of the blood-brain barrier (BBB) are often performed in
      rats. We describe the functional characterization of a reproducible in vitro
      model of the rat BBB and its validation for investigating mechanisms involved in
      BBB regulation. Puromycin-purified primary cultures of brain endothelial cells,
      co-cultured with astrocytes in the presence of hydrocortisone (HC) and cAMP,
      presented low sucrose permeability (< or =0.1 x 10(-3) cm/min) and high
      transendothelial electrical resistance (> or =270 Omega cm(2)). Expression of
      specific BBB markers and their transcripts was detected by immunostaining and RT
      PCR, respectively: tight junction proteins (claudin-3 and -5, ZO-1 and occludin)
      and transporters (P-gp, Bcrp and Oatp-2). RT-PCR experiments demonstrated a role
      of treatment by astrocytes, HC and cAMP in regulation of the transcript level of
      tight junction proteins (claudin-5 and ZO-1) as well as transporters (Mdr1a,
      Mrp3, Mrp4, Bcrp, Glut-1), while transcript level of Mdr1b was significantly
      decreased. The functionality of efflux pumps (P-gp, Mrps and Bcrp) was
      demonstrated in the presence of specific inhibitors (PSC833, MK571 or Ko143,
      respectively) by (i) assessing the uptake of the common substrates rhodamine 123
      and daunorubicin and (ii) evaluating apical to basolateral and basolateral to
      apical polarized transport of daunorubicin. In addition, a good correlation
      (R=0.94) was obtained between the permeability coefficients of a series of
      compounds of various lipophilicity and their corresponding in vivo rodent blood
      brain transfer coefficients. Taken together, our results provide compelling
      evidence that puromycin-purified rat brain endothelial cells constitute a
      reliable model of the rat BBB for physiological and pharmacological
      characterization of BBB transporters.

PMID- 17434464
TI  - Neonatal maternal separation enhances central sensitivity to noxious colorectal
      distention in rat.
AB  - Psychological stress experienced in early life plays an important role in the
      development of visceral hyperalgesia in irritable bowel syndrome (IBS). Neonatal
      maternal separation has been shown to trigger a long-term alternation in stress
      induced responses to visceral nociceptive stimuli in rats. The aim of the present
      study was to show a direct evidence of stress-induced alteration in central
      neuronal responses to colorectal distention (CRD) in rats by a quantitative study
      of c-fos expression in relevant brain structures. Male Wistar rat pups were
      subjected to 180-min daily neonatal maternal separation (NMS) for 13 consecutive
      days (from PND 2 to PND 14). The expression of c-fos was examined by using
      immunohistochemistry. Increased c-fos expression was observed, for the first
      time, in the cingulate cortex (3-fold) in NMS rats in comparison with the control
      group at basal condition. At noxious CRD (80 mm Hg), c-fos expression was induced
      in the supraspinal centers and in both the superficial (laminae I-II) and the
      deeper laminae (laminae V-VI and X) of the spinal cord in rats. Significantly
      more Fos-IR nuclei were found in the laminae I and II, and laminae V-VI of the
      lumbarsacral spinal cord, the paraventricular thalamic nucleus, the cingulate
      cortex, the amygdaloid central nucleus in NMS rats, but not in the solitary
      tract, the central medial thalamic nucleus, the ventromedial hypothalamic
      nucleus, and the periaquaductal gray. The present results indicate that NMS has
      sensitized the cingulate cortex and upregulated the activity of the ascending
      pathway at spinal level as well as the thalamo-cortico-amydala pathway to CRD.
      The upregulation and sensitization of these pathways may be responsible for the
      development of visceral hypersensitivity in IBS.

PMID- 17434465
TI  - Evaluation of the mGlu8 receptor as a putative therapeutic target in
      schizophrenia.
AB  - Aberrant glutamatergic neurotransmission may underlie the pathogenesis of
      schizophrenia and metabotropic glutamate receptors (mGluRs) have been implicated
      in the disease. We have established the localization of the group III mGluR
      subtype, mGluR8, in the human body and investigated the biological effects of the
      selective mGluR8 agonist (S)-3,4-dicarboxyphenylglycine ((S)-3,4-DCPG) in
      schizophrenia-related animal models. The mGlu8 receptor has a widespread CNS
      distribution with expression observed in key brain regions associated with
      schizophrenia pathogenesis including the hippocampus. (S)-3,4-DCPG inhibited
      synaptic transmission and increased paired-pulse facilitation in rat hippocampal
      slices supporting the role of mGluR8 as a presynaptic autoreceptor. Using the rat
      Maximal Electroshock Seizure Threshold (MEST) test, (S)-3,4-DCPG (30 mg/kg, i.p.)
      reduced seizure activity confirming the compound to be centrally active following
      systemic administration. (S)-3,4-DCPG did not reverse (locomotor) hyperactivity
      induced by acute administration of phenylcyclidine (PCP, 1-32 mg/kg, i.p.) or
      amphetamine (3-30 mg/kg, i.p.) in Sprague-Dawley rats. However, 10 nmol (i.c.v.)
      (S)-3.4-DCPG did reverse amphetamine-induced hyperactivity in mice although it
      also inhibited spontaneous locomotor activity at this dose. In addition, mGluR8
      null mutant mouse behavioral phenotyping revealed an anxiety-related phenotype
      but no deficit in sensorimotor gating. These data provide a potential role for
      mGluR8 in anxiety and suggest that mGluR8 may not be a therapeutic target for
      schizophrenia.

PMID- 17434466
TI  - Nf-kappab and AP-1 activation is associated with late lumen loss after porcine
      coronary angioplasty and antiproliferative beta-irradiation.
AB  - OBJECTIVE: Despite the success of antiproliferative therapies, restenosis remains
      a common problem after percutaneous transluminal coronary angioplasty (PTCA).
      Longer-term clinical results of brachytherapy (intracoronary radiation), the lack
      of long-term clinical results after implantation of drug eluting stents, and the
      occurrence of late thrombosis after both procedures leave room for skepticism.
      Neointimal proliferation is not substantially inhibited at late time points after
      brachytherapy, and late lumen loss with a "catch-up" proliferation can occur. We
      hypothesized that the transcription factors nuclear factor-{kappa}B (NF-kappaB)
      and activator protein-1 (AP-1) are involved in these processes. We addressed the
      role of these mediators in a porcine model of coronary restenosis. METHODS:
      Thirty-nine pigs underwent PTCA in two major coronary arteries. One of the two
      balloon-injured arteries was randomly assigned to receive immediate 20 Gy beta
      irradiation (Brachy group) using a noncentered source train ((90)Sr/Y Beta-Cath,
      Novoste). Animals were sacrificed after 1 day, 14 days, or 28 days. Proliferating
      cells were labeled prior to euthanasia. RESULTS: At late time points, lumen area
      was significantly smaller and the inflammatory response was more pronounced in
      the Brachy group than in the PTCA group. These findings coincided with sustained
      activation of MMP-9 and transcription factors like NF-kappaB and AP-1. Initially,
      cell proliferation was reduced in the Brachy group; however, at late time points,
      differences between the two treatment groups were no longer significant.
      CONCLUSIONS: Brachytherapy initially inhibits cell proliferation; however,
      cellular and molecular inflammatory processes (e.g. activation of NF-kappaB) are
      enhanced within the arterial wall. This proinflammatory side effect may be
      responsible for the observed delayed proliferation and the resulting lumen loss.

PMID- 17434467
TI  - Genomics of TGF-beta1 signaling in stem cell commitment and dendritic cell
      development.
AB  - Dendritic cells are professional antigen presenting cells and central for
      establishing and maintaining immunity and immunological tolerance. They develop
      from hematopoietic stem cells through successive steps of lineage commitment and
      differentiation. Dendritic cell development and function are regulated by
      specific cytokines, including transforming growth factor type beta1 (TGF-beta1).
      Our previous work demonstrated the importance of TGF-beta1 signaling for
      dendritic cell development and subset specification. Here, we used genome-wide
      gene expression profiling with DNA microarrays to investigate the activity of TGF
      beta1 on gene expression in dendritic cell development. This study identified
      specific gene categories induced by TGF-beta1 with an impact on dendritic cell
      biology.

PMID- 17434468
TI  - Lineage tree analysis of immunoglobulin variable-region gene mutations in
      autoimmune diseases: chronic activation, normal selection.
AB  - Autoimmune diseases show high diversity in the affected organs, clinical
      manifestations and disease dynamics. Yet they all share common features, such as
      the ectopic germinal centers found in many affected tissues. Lineage trees depict
      the diversification, via somatic hypermutation (SHM), of immunoglobulin variable
      region (IGV) genes. We previously developed an algorithm for quantifying the
      graphical properties of IGV gene lineage trees, allowing evaluation of the
      dynamical interplay between SHM and antigen-driven selection in different
      lymphoid tissues, species, and disease situations. Here, we apply this method to
      ectopic GC B cell clones from patients with Myasthenia Gravis, Rheumatoid
      Arthritis, and Sjogren's Syndrome, using data scaling to minimize the effects of
      the large variability due to methodological differences between groups.
      Autoimmune trees were found to be significantly larger relative to normal
      controls. In contrast, comparison of the measurements for tree branching
      indicated that similar selection pressure operates on autoimmune and normal
      control clones.

PMID- 17434469
TI  - Bioinformatics applied to allergy: allergen databases, from collecting sequence
      information to data integration. The Allergome platform as a model.
AB  - Allergens are proteins or glycoproteins that are recognized by IgE produced by
      the immune system of allergic individuals. Until now around 1,500 allergenic
      structures have been identified and this number seems not have reached a plateau
      after 3-4 decades of research and the advent of molecular biology. Several
      allergen databases are available on Internet. Different aims and philosophies
      lead to different products. Here we report about main feature of web sites
      dedicated to allergens and we describe in more details our current work on the
      Allergome platform. The web server Allergome (www.allergome.org) represent a free
      independent open resource whose goal is to provide an exhaustive repository of
      data related to all the IgE-binding compounds. The main purpose of Allergome is
      to collect a list of allergenic sources and molecules by using the widest
      selection criteria and sources. A further development of the Allergome platform
      has been represented by the Real Time Monitoring of IgE sensitization module
      (ReTiME) that allows uploading of raw data from both in vivo and in vitro
      testing, thus representing the first attempt to have IT applied to allergy data
      mining. More recently, a new module (RefArray) representing a tool for literature
      mining has been released.

PMID- 17434470
TI  - Comparison of immune assays for the detection of anti-HSP70 antibodies in
      patients with idiopathic sensorineural hearing loss.
AB  - BACKGROUND: Detection of anti-heat-shock protein 70 (HSP70) IgG response by
      Western blot (WB) is of clinical utility in a subset of patients with idiopathic
      sensorineural hearing loss (SNHL) due to autoimmunity. METHODS: To validate an
      immune assay for the detection of anti-HSP70 antibody responses in the clinical
      laboratory, we employed a commercial anti-human HSP70 IgG/A/M ELISA and developed
      an anti-HSP70 IgG WB test. Using sera from 81 patients with idiopathic SNHL and
      100 healthy controls, we assessed each assay performance with results from
      another diagnostic laboratory that utilizes a WB test. RESULTS: Our results
      showed a significant lack of agreement between either WB assay and the anti-human
      HSP70 IgG/A/M ELISA for antibody-positive samples. Comparison of WB assays
      revealed a significant level of agreement (89.7%) for all samples tested.
      CONCLUSIONS: Our data suggest that the antigenic targets in WB and ELISA
      immunoassays differ and demonstrate that the anti-HSP70 IgG WB test is
      reproducible within and between clinical laboratories. Thus, in the absence of
      disease-specific markers, the anti-HSP70 IgG WB assay could be of use to detect
      patients with idiopathic SNHL who might benefit from steroid treatment.

PMID- 17434471
TI  - Characterization of dSnoN and its relationship to Decapentaplegic signaling in
      Drosophila.
AB  - Vertebrate members of the ski/snoN family of proto-oncogenes antagonize TGFbeta
      and BMP signaling in a variety of experimental situations. This activity of
      Ski/SnoN proteins is related to their ability to interact with Smads, the
      proteins acting as key mediators of the transcriptional response to the TGFbeta
      superfamily members. However, despite extensive efforts to identify the
      physiological roles of the Ski/SnoN proteins, it is not yet clear whether they
      participate in regulating Activin and/or BMP signaling during normal development.
      It is therefore crucial to examine their roles in vivo mostly because of the
      large number of known Ski/SnoN-interacting proteins and the association between
      the up-regulation of these genes and cancer progression. Here we characterize the
      Drosophila homolog to vertebrate ski and snoN genes. The Drosophila dSnoN protein
      retains the ability of its vertebrate counterparts to antagonize BMP signaling in
      vivo and in cultured cells. dSnoN does not interfere with Mad phosphorylation but
      it interacts genetically with Mad, Medea and dSmad2. Mutations in either the
      Smad2-3 or Smad4 putative binding sites of dSnoN prevent the antagonism of dSnoN
      towards Dpp signaling, although homozygous flies for these mutations or for a
      genetic deficiency of the locus are viable and have wings of normal size and
      pattern.

PMID- 17434472
TI  - Distinct mechanisms for mRNA localization during embryonic axis specification in
      the wasp Nasonia.
AB  - mRNA localization is a powerful mechanism for targeting factors to different
      regions of the cell and is used in Drosophila to pattern the early embryo. During
      oogenesis of the wasp Nasonia, mRNA localization is used extensively to replace
      the function of the Drosophila bicoid gene for the initiation of patterning along
      the antero-posterior axis. Nasonia localizes both caudal and nanos to the
      posterior pole, whereas giant mRNA is localized to the anterior pole of the
      oocyte; orthodenticle1 (otd1) is localized to both the anterior and posterior
      poles. The abundance of differentially localized mRNAs during Nasonia oogenesis
      provided a unique opportunity to study the different mechanisms involved in mRNA
      localization. Through pharmacological disruption of the microtubule network, we
      found that both anterior otd1 and giant, as well as posterior caudal mRNA
      localization was microtubule-dependent. Conversely, posterior otd1 and nanos mRNA
      localized correctly to the posterior upon microtubule disruption. However, actin
      is important in anchoring these two posteriorly localized mRNAs to the oosome,
      the structure containing the pole plasm. Moreover, we find that knocking down the
      functions of the genes tudor and Bicaudal-D mimics disruption of microtubules,
      suggesting that tudor's function in Nasonia is different from flies, where it is
      involved in formation of the pole plasm.

PMID- 17434473
TI  - The SynMuv genes of Caenorhabditis elegans in vulval development and beyond.
AB  - For a nonessential diminutive organ comprised of only 22 nuclei, the
      Caenorhabditis elegans vulva has done very well for itself. The status of the
      vulva as an overachiever is in part due to its inherent structural simplicity as
      well as to the intricate regulation of its induction and development. Studies
      over the past twenty years have shown the vulva to be a microcosm for
      organogenesis and a model for the integration of complex signaling pathways.
      Furthermore, many of these signaling molecules are themselves associated with
      cancer in mammals. This review focuses on what is perhaps the most intriguing and
      complex story to emerge from these studies thus far, the role of the Synthetic
      Multivulval (SynMuv) genes in controlling vulval cell-fate adoption. Recent
      advances have led to a greater mechanistic understanding of how these genes
      function during vulval development and have also identified roles for these genes
      in diverse developmental processes.

PMID- 17434474
TI  - Alterations of rx1 and pax6 expression levels at neural plate stages
      differentially affect the production of retinal cell types and maintenance of
      retinal stem cell qualities.
AB  - rx1 and pax6 are necessary for the establishment of the vertebrate eye field and
      for the maintenance of the retinal stem cells that give rise to multiple retinal
      cell types. They also are differentially expressed in cellular layers in the
      retina when cell fates are being specified, and their expression levels
      differentially affect the production of amacrine cell subtypes. To determine
      whether rx1 and pax6 expression after the eye field is established simply
      maintains stem cell-like qualities or affects cell type differentiation, we used
      hormone-inducible constructs to increase or decrease levels/activity of each
      protein at two different neural plate stages. Our results indicate that rx1
      regulates the size of the retinal stem cell pool because it broadly affected all
      cell types, whereas pax6 regulates more restricted retinal progenitor cells
      because it selectively affected different cell types in a time-dependent manner.
      Analysis of rx1 and pax6 effects on proliferation, and expression of stem cell or
      differentiation markers demonstrates that rx1 maintains cells in a stem cell
      state by promoting proliferation and delaying expression of neural identity and
      differentiation markers. Although pax6 also promotes proliferation, it
      differentially regulates neural identity and differentiation genes. Thus, these
      two genes work in parallel to regulate different, but overlapping aspects of
      retinal cell fate determination.

PMID- 17434475
TI  - Gypenoside XLIX, a naturally occurring PPAR-alpha activator, inhibits cytokine
      induced vascular cell adhesion molecule-1 expression and activity in human
      endothelial cells.
AB  - Vascular cell adhesion molecule-1 (VCAM-1) is involved in several diseases,
      including chronic inflammation and atherosclerosis. Inhibition of the expression
      of this adhesion molecule is one of the key targets of anti-inflammatory, anti
      cancer and anti-atherosclerotic drugs. Gynostemma pentaphyllum is a traditional
      medicine widely used in the treatment of respiratory inflammation, hyperlipidemia
      and atherosclerosis. However, its molecular mechanisms of action are still
      largely unknown. Gypenoside XLIX, a dammarane-type glycoside, is a prominent
      component of G. pentaphyllum. We have recently demonstrated Gypenoside XLIX to be
      a selective peroxisome proliferator-activated receptor (PPAR)-alpha activator.
      Here we demonstrate that Gypenoside XLIX concentration-dependently (0-300 microM)
      inhibited VCAM-1 promoter activity after induction by cytokine tumor necrosis
      factor (TNF)-alpha in human umbilical vein endothelial cells (HUVECs) transfected
      with promoter-reporter construct pVCAM-1-LUC. Furthermore, Gypenoside XLIX
      inhibited TNF-alpha-induced VCAM-1 mRNA and protein overexpression in HUVECs. The
      result of the enzyme immunoassay demonstrated that Gypenoside XLIX inhibited TNF
      alpha-induced increase in cell surface VCAM-1 protein levels in HUVECs. In the
      present study we show that activities of Gypenoside XLIX are similar to those of
      Wy-14643, a potent synthetic PPAR-alpha activator. Furthermore, Gypenoside XLIX
      induced inhibition on TNF-alpha-stimulated VCAM-1 promoter hyperactivity was
      completely abolished by a selective blocker of PPAR-alpha, MK-886. Thus, our
      findings suggest that Gypenoside XLIX inhibits cytokine-induced VCAM-1
      overexpression and hyperactivity in human endothelial cells via a PPAR-alpha
      dependent pathway. These data provide new insight into the rational basis of the
      use of the traditional Chinese herbal medicine G. pentaphyllum in the treatment
      of inflammatory and cardiovascular diseases, including atherosclerosis.

PMID- 17434476
TI  - Effect of silymarin on pyrogallol- and rifampicin-induced hepatotoxicity in
      mouse.
AB  - Rifampicin and pyrogallol, besides beneficial effects, elicit hepatotoxicity in
      experimental animals and humans. The present investigation was undertaken to
      elucidate the role of drug/toxicant-metabolizing enzymes in rifampicin- and
      pyrogallol-induced hepatotoxicity and the effect of silymarin, a herbal
      antioxidant, on rifampicin- and pyrogallol-induced alterations in mouse liver.
      Male Swiss albino mice were treated intraperitoneally with and without rifampicin
      (20 mg/kg) and/or pyrogallol (40 mg/kg) for 1, 2, 3 and 4 weeks. In some
      experiments, animals were treated with silymarin (40 mg/kg), 2 h prior to
      rifampicin and/or pyrogallol. The differential expression and catalytic activity
      of cytochrome P-450 (CYP) 1A1, CYP1A2 and CYP2E1, the activity of glutathione-S
      transferase, glutathione peroxidase and glutathione reductase, and lipid
      peroxidation were measured in the liver of control and treated groups. CYP1A1
      expression and catalytic activity were not altered following individual or
      combinational treatment. A significant augmentation in the expression and
      activity of CYP1A2 and CYP2E1 was observed following pyrogallol and
      rifampicin+pyrogallol treatment; however, rifampicin exhibited a significant
      induction of CYP2E1 only. Attenuation of glutathione-S-transferase, glutathione
      reductase and glutathione peroxidase activities and augmentation of lipid
      peroxidation were observed following rifampicin and/or pyrogallol treatment and a
      cumulative effect was seen when the two drugs were administered in combination.
      Silymarin restored the rifampicin- and/or pyrogallol-induced alterations in the
      expression and activity of CYP1A2 and CYP2E1, the activity of glutathione-S
      transferase, glutathione reductase, and glutathione peroxidase, and lipid
      peroxidation. The results demonstrate the role of CYP1A2, CYP2E1, glutathione-S
      transferase, glutathione reductase and glutathione peroxidase in rifampicin- and
      pyrogallol-induced hepatotoxicity and provide evidence for the involvement of
      silymarin in attenuation of drug-induced hepatotoxicity.

PMID- 17434477
TI  - Clioquinol attenuates zinc-dependent beta-cell death and the onset of insulitis
      and hyperglycemia associated with experimental type I diabetes in mice.
AB  - Zinc in the pancreas is co-released with insulin from beta-cells reaching
      concentrations similar to those found in the vicinity of glutamatergic synapses.
      In the brain, the role of zinc in excitotoxic brain damage is well established.
      In contrast, its role in islet destruction during diabetes is poorly understood.
      We have studied the efficacy of zinc homeostatic proteins and an intracellular
      zinc chelator, clioquinol, in conferring resistance against zinc toxicity in
      pancreatic islets. We further assessed the ability of clioquinol to protect the
      islets in an experimental model of type I diabetes. Our results indicate that
      endogenous mechanisms for lowering [Zn]i are deficient in the insulinoma cell
      line, MIN6, and that permeation of Zn2+ triggered cell death. Application of the
      low affinity, intracellular zinc chelator, clioquinol, reduced Zn2+-induced cell
      death by 80%. In addition, chelation of zinc ions by clioquinol in vivo prevented
      onset of multiple low dose streptozotocin-induced diabetes, and reduced the
      insulitis and hyperglycemia associated with this model. Furthermore, the glucose
      tolerance test (GTT) score of multiple low dose streptozotocin (MLD-STZ) mice
      pretreated with clioquinol was, statistically indistinguishable from that of
      untreated, control mice. Taken together, our results point to the potential
      utility of in vivo zinc chelation as a therapeutic strategy for treatment of
      idiopathic type I diabetes.

PMID- 17434478
TI  - Coenzyme Q10 prevents high glucose-induced oxidative stress in human umbilical
      vein endothelial cells.
AB  - Hyperglycemia-induced oxidative stress plays a crucial role in the pathogenesis
      of vascular complications in diabetes. Although some clinical evidences suggest
      the use of an antioxidant reagent coenzyme Q10 in diabetes with hypertension, the
      direct effect of coenzyme Q10 on the endothelial functions has not been examined.
      In the present study, we therefore investigated the protective effect of coenzyme
      Q10 against high glucose-induced oxidative stress in human umbilical vein
      endothelial cells (HUVEC). HUVEC exposed to high glucose (30 mM) exhibited
      abnormal properties, including the morphological and biochemical features of
      apoptosis, overproduction of reactive oxygen species, activation of protein
      kinase Cbeta2, and increase in endothelial nitric oxide synthase expression.
      Treatment with coenzyme Q10 strongly inhibited these changes in HUVEC under high
      glucose condition. In addition, coenzyme Q10 inhibited high glucose-induced
      cleavage of poly(ADP-ribose) polymerase, an endogenous caspase-3 substrate. These
      results suggest that coenzyme Q10 prevents reactive oxygen species-induced
      apoptosis through inhibition of the mitochondria-dependent caspase-3 pathway.
      Moreover, consistent with previous reports, high glucose caused upregulation of
      intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1
      (VCAM-1) in HUVEC, and promoted the adhesion of U937 monocytic cells. Coenzyme
      Q10 displayed potent inhibitory effects against these endothelial abnormalities.
      Thus, we provide the first evidence that coenzyme Q10 has a beneficial effect in
      protecting against the endothelial dysfunction by high glucose-induced oxidative
      stress in vitro.

PMID- 17434479
TI  - Synergistic antinociception by the cannabinoid receptor agonist anandamide and
      the PPAR-alpha receptor agonist GW7647.
AB  - The analgesic properties of cannabinoid receptor agonists are well characterized.
      However, numerous side effects limit the therapeutic potential of these agents.
      Here we report a synergistic antinociceptive interaction between the endogenous
      cannabinoid receptor agonist anandamide and the synthetic peroxisome proliferator
      activated receptor-alpha (PPAR-alpha) agonist 2-(4-(2-(1-Cyclohexanebutyl)-3
      cyclohexylureido)ethyl)phenylthio)-2-methylpropionic acid (GW7647) in a model of
      acute chemical-induced pain. Moreover, we show that anandamide synergistically
      interacts with the large-conductance potassium channel (KCa1.1, BK) activator
      isopimaric acid. These findings reveal a synergistic interaction between the
      endocannabinoid and PPAR-alpha systems that might be exploited clinically and
      identify a new pharmacological effect of the BK channel activator isopimaric
      acid.

PMID- 17434480
TI  - Pharmacological studies with a nonpeptidic, delta-opioid (-)-(1R,5R,9R)-5,9
      dimethyl-2'-hydroxy-2-(6-hydroxyhexyl)-6,7-benzomorphan hydrochloride ((-)-NIH
      11082).
AB  - In the search for a selective delta-opioid receptor agonist, (-)-(1R,5R,9R)-5,9
      dimethyl-2'-hydroxy-2-(6-hydroxyhexyl)-6,7-benzomorphan hydrochloride ((-)-NIH
      11082) and the (+)-enantiomer were synthesized and tested. (-)-NIH 11082
      displayed antinociceptive activity in the paraphenylquinone test (PPQ test) in
      male ICR mice [ED50=1.9 (0.7-5.3) mg/kg, s.c.] and showed little, if any,
      activity in the tail-flick and hot-plate assays. The (+)-enantiomer was
      essentially inactive indicating stereoselectivity. Opioid receptor subtype
      characterization studies indicated that naltrindole, a delta-opioid receptor
      antagonist, was potent versus the ED80 of (-)-NIH 11082 in the PPQ test
      [AD50=0.75 (0.26-2.20) mg/kg, s.c]. beta-Funaltrexamine and nor-binaltorphimine,
      selective mu- and kappa-receptor antagonists, respectively, were inactive versus
      the ED80 of (-)-NIH 11082. In rats with inflammation-induced pain, (-)-NIH 11082
      produced antihyperalgesic effects that were attenuated by naltrindole. In
      morphine-dependent rhesus monkeys of both sexes, (-)-NIH 11082 neither
      substituted for morphine nor exacerbated withdrawal signs in the dose range of
      4.0 to 32.0 mg/kg, s.c. Neither convulsions nor other overt behavioral signs were
      observed in any of the species tested. The results indicate that (-)-NIH 11082
      has delta-opioid receptor properties.

PMID- 17434481
TI  - Comparison of mitochondrial and macrophage content between subcutaneous and
      visceral fat in db/db mice.
AB  - Central (visceral) obesity is more closely associated with insulin resistance,
      type 2 diabetes, and cardiovascular disease than peripheral (subcutaneous)
      obesity, however the underlying differences in morphology and pathophysiology
      between subcutaneous and visceral adipose are largely unknown. To evaluate the
      effects of diabetes and rosiglitazone (RSG) treatment, the expression of
      mitochondrial Hsp60, UCP-1 and F4/80 in inguinal subcutaneous (SC) fat, composed
      of white and brown adipose tissues, and epididymal (EP) fat, mainly white adipose
      tissue, were evaluated. In diabetic db/db mice, there was significant increased
      number of aggregated macrophage foci compared to db/+ mice, especially in EP fat.
      On the other hand, the expression of mitochondrial Hsp60 protein was suppressed
      in both SC and EP fat of db/db mice compared to db/+ mice, and the expression
      level of mitochondrial Hsp60 in db/+ mice was lower in EP fat compared with SC.
      In db/db mice, RSG suppressed the number of aggregated macrophage foci in EP fat,
      but not in SC fat. RSG ameliorated the mitochondrial Hsp60 expression and induced
      the expression of UCP-1 in both SC and EP fat. Taken together, these data suggest
      that differences exist in mitochondrial and macrophage content, and in the
      response to RSG between visceral and subcutaneous adipose tissue, and adipose
      type and distribution may be important for obesity-linked insulin resistance.

PMID- 17434482
TI  - Structural and regulatory functions of keratins.
AB  - The diversity of epithelial functions is reflected by the expression of distinct
      keratin pairs that are responsible to protect epithelial cells against mechanical
      stress and to act as signaling platforms. The keratin cytoskeleton integrates
      these functions by forming a supracellular scaffold that connects at desmosomal
      cell-cell adhesions. Multiple human diseases and murine knockouts in which the
      integrity of this system is destroyed testify to its importance as a mechanical
      stabilizer in certain epithelia. Yet, surprisingly little is known about the
      precise mechanisms responsible for assembly and disease pathology. In addition to
      these structural aspects of keratin function, experimental evidence accumulating
      in recent years has led to a much more complex view of the keratin cytoskeleton.
      Distinct keratins emerge as highly dynamic scaffolds in different settings and
      contribute to cell size determination, translation control, proliferation, cell
      type-specific organelle transport, malignant transformation and various stress
      responses. All of these properties are controlled by highly complex patterns of
      phosphorylation and molecular associations.

PMID- 17434483
TI  - Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding
      with changes in morphology and function of tight junctions.
AB  - In rodent livers, integral tight junction (TJ) proteins claudin-1, -2, -3, -5 and
      -14 are detected and play crucial roles in the barrier to keep bile in bile
      canaculi away from the blood circulation. Claudin-2 shows a lobular gradient
      increasing from periportal to pericentral hepatocytes, whereas claudin-1 and -3
      are expressed in the whole liver lobule. Although claudin-2 expression induces
      cation-selective channels in tight junctions of epithelial cells, the
      physiological functions and regulation of claudin-2 in hepatocytes remain
      unclear. Oncostatin M (OSM) is a multifunctional cytokine implicated in the
      differentiation of hepatocytes that induces formation of E-cadherin-based
      adherens junctions in fetal hepatocytes. In this study, we examined whether OSM
      could induce expression and function of claudin-2 in rodent hepatocytes,
      immortalized mouse and primary cultured proliferative rat hepatocytes. In the
      immortalized mouse and primary cultured proliferative rat hepatocytes, treatment
      with OSM markedly increased mRNA and protein of claudin-2 together with formation
      of developed networks of TJ strands. The increase of claudin-2 enhanced the
      paracellular barrier function which depended on molecular size. The increase of
      claudin-2 expression induced by OSM in rodent hepatocytes was regulated through
      distinct signaling pathways including PKC. These results suggest that expression
      of claudin-2 in rodent hepatocytes may play a specific role as controlling the
      size of paracellular permeability in the barrier to keep bile in bile canaculi.

PMID- 17434484
TI  - Two-dimensional order in mammalian pre-ocular tear film.
AB  - We report a grazing incidence x-ray diffraction (GIXD) investigation of the
      surface lipid layer of the pre-ocular tear film. For the first time we
      demonstrate the existence of 2D order over a wide range of surface pressures in
      this system, with typical spicing of 3.75A and 4.16A independent of the monolayer
      surface pressure. Analogous lipid ordering is also found in an artificial lipid
      mixture of the major lipid components of the tear film, suggesting that the 2D
      ordering is set by generic lipid-lipid interactions. Fluorescence microscopy of
      the natural and artificial tear film mixture reveals the co-existence of a dilute
      and a much more condensed phase in the amphiphilic lipid matrix over the pressure
      range of 15-45mN/m investigated by GIXD, plus an additional structure due to the
      much more hydrophobic part of the mixture. This evidence supports the previous
      hypothesis that tear film has a layered structure.

PMID- 17434485
TI  - Pathogenic mitochondrial DNA-induced respiration defects in hematopoietic cells
      result in anemia by suppressing erythroid differentiation.
AB  - Anemia is a symptom in patients with Pearson syndrome caused by the accumulation
      of mutated mitochondrial DNA (mtDNA). Such mutated mtDNAs have been detected in
      patients with anemia. This suggested that respiration defects due to mutated
      mtDNA are responsible for the anemia. However, there has been no convincing
      experimental evidence to confirm the pathophysiological relation between
      respiration defects in hematopoietic cells and expression of anemia. We address
      this issue by transplanting bone marrow cells carrying pathogenic mtDNA with a
      large-scale deletion (DeltamtDNA) into normal mice. The bone marrow-transplanted
      mice carried high proportion of DeltamtDNA only in hematopoietic cells, and
      resultant the mice suffered from macrocytic anemia. They show abnormalities of
      erythroid differentiation and weak erythropoietic response to a stressful
      condition. These observations suggest that hematopoietic cell-specific
      respiration defects caused by mtDNAs with pathogenic mutations are responsible
      for anemia by inducing abnormalities in erythropoiesis.

PMID- 17434486
TI  - PRI-Modeler: extracting RNA structural elements from PDB files of protein-RNA
      complexes.
AB  - A complete understanding of protein and RNA structures and their interactions is
      important for determining the binding sites in protein-RNA complexes.
      Computational approaches exist for identifying secondary structural elements in
      proteins from atomic coordinates. However, similar methods have not been
      developed for RNA, due in part to the very limited structural data so far
      available. We have developed a set of algorithms for extracting and visualizing
      secondary and tertiary structures of RNA and for analyzing protein-RNA complexes.
      These algorithms have been implemented in a web-based program called PRI-Modeler
      (protein-RNA interaction modeler). Given one or more protein data bank files of
      protein-RNA complexes, PRI-Modeler analyzes the conformation of the RNA,
      calculates the hydrogen bond (H bond) and van der Waals interactions between
      amino acids and nucleotides, extracts secondary and tertiary RNA structure
      elements, and identifies the patterns of interactions between the proteins and
      RNAs. This paper presents PRI-Modeler and its application to the hydrogen bond
      and van der Waals interactions in the most representative set of protein-RNA
      complexes. The analysis reveals several interesting interaction patterns at
      various levels. The information provided by PRI-Modeler should prove useful for
      determining the binding sites in protein-RNA complexes. PRI-Modeler is accessible
      at http://wilab.inha.ac.kr/primodeler/, and supplementary materials are available
      in the analysis results section at http://wilab.inha.ac.kr/primodeler/.

PMID- 17434487
TI  - Glucose repression over Saccharomyces cerevisiae glycerol/H+ symporter gene STL1
      is overcome by high temperature.
AB  - High temperature promotes an improved activity of the Saccharomyces cerevisiae
      glycerol/H(+) symporter encoded by STL1, which correlates well with Stl1p levels.
      This happens in both fermentable and respiratory metabolic growth conditions,
      though the induction in the latter is much higher. The relief of glucose
      repression by high temperature at the level of protein expression and activity
      (Stl1p) is reported for the first time. We reason that the glycerol internal
      levels fine-tuning, under heat-stress as in other physiological condition, can be
      achieved with the contribution of the tight regulation of the symporter.

PMID- 17434488
TI  - Osmoregulation of leaf motor cells.
AB  - "Osmotic Motors"--the best-documented explanation for plant leaf movements-
      frequently reside in specialized motor leaf organs, pulvini. The movements result
      from dissimilar volume and turgor changes in two oppositely positioned parts of
      the pulvinus. This Osmotic Motor is powered by a plasma membrane proton ATPase,
      which drives KCl fluxes and, consequently, water, across the pulvinus into
      swelling cells and out of shrinking cells. Light signals and signals from the
      endogenous biological clock converge on the channels through which these fluxes
      occur. These channels and their regulatory pathways in the pulvinus are the topic
      of this review.

PMID- 17434489
TI  - Advanced glycation end products increases matrix metalloproteinase-1, -3, and 
      13, and TNF-alpha in human osteoarthritic chondrocytes.
AB  - We investigated the effects of advanced glycation end products (AGE) which
      accumulate in articular cartilage with age in human osteoarthritic chondrocytes.
      We found AGE-BSA significantly increased MMP-1, -3, and -13, and TNF-alpha in a
      dose-dependent manner. AGE-BSA-stimulated JNK, p38, and ERK and NF-kappaB
      activity. The stimulatory effect of AGE-BSA on MMP-1, -3, and -13 were reversed
      by treatment with specific JNK, p38 inhibitors, suggesting JNK and p38 are
      involved in AGE-BSA-induced MMPs and TNF-alpha. We also observed that NF-kappaB
      is involved in AGE-BSA-induced TNF-alpha. Pretreatment with soluble receptor for
      AGE (sRAGE) also reduced AGE-stimulated MMPs and TNF-alpha, implicating the
      involvement of receptor for AGE (RAGE). In conclusion, accumulation of AGE may
      have a role in the development of osteoarthritis by increasing MMP-1, -3, and 
      13, and TNF-alpha.

PMID- 17434490
TI  - Anion channels and transporters in plant cell membranes.
AB  - Anion channels/transporters appear as key players in signaling pathways leading
      to the adaptation of plant cells to abiotic and biotic environmental stresses, in
      the control of metabolism and in the maintenance of electrochemical gradients.
      Focusing on the most recent advances, this review aims at providing a description
      of the role of these channels in various physiological functions such as control
      of stomatal movements, plant-pathogen interaction, xylem loading,
      compartmentalization of metabolites and coupling with proton gradients. These
      functions have been demonstrated by a combination of electrophysiology,
      pharmacology and genetics approaches, the key issue being to identify the
      corresponding proteins and genes.

PMID- 17434491
TI  - Gene expression signatures in the newt irises during lens regeneration.
AB  - Lens regeneration in adult newts is possible by transdifferentiation of the
      pigment epithelial cells (PECs) of the dorsal iris. The same cells in the ventral
      iris are not capable of such a process. To understand this difference in
      regenerative competency, we examined gene expression of 373 genes in the intact
      dorsal and ventral irises as well as in irises during the process of lens
      regeneration. We found similar signatures of gene expression in dorsal and
      ventral with several cases of even higher levels in the ventral iris. Such
      transcriptional activity in the regeneration-incompetent ventral iris was
      unexpected and calls for a revision of our views about mechanisms of lens
      regeneration induction.

PMID- 17434492
TI  - Probing the nucleotide binding and phosphorylation by the histidine kinase of a
      novel three-protein two-component system from Mycobacterium tuberculosis.
AB  - The two-component signal transduction system from Mycobacterium tuberculosis
      bears a unique three-protein system comprising of two putative histidine kinases
      (HK1 and HK2) and one response regulator TcrA. By sequence analysis, HK1 is found
      to be an adenosine 5'-triphosphate (ATP) binding protein, similar to the
      nucleotide-binding domain of homologous histidine kinases, and HK2 is a unique
      histidine containing phosphotransfer (HPt)-mono-domain protein. HK1 is expected
      to interact with and phosphorylate HK2. Here, we show that HK1 binds 2'(3')-O
      (2,4,6-trinitrophenyl)adenosine 5'-triphosphate monolithium trisodium salt and
      ATP with a 1:1 stoichiometric ratio. The ATPase activity of HK1 in the presence
      of HK2 was measured, and phosphorylation experiments suggested that HK1 acts as a
      functional kinase and phosphorylates HK2 by interacting with it. Further
      phosphorylation studies showed transfer of a phosphoryl group from HK2 to the
      response regulator TcrA. These results indicate a new mode of interaction for
      phosphotransfer between the two-component system proteins in bacteria.

PMID- 17434493
TI  - Structural characterization of dimeric murine aminoacylase III.
AB  - Aminoacylase III (AAIII) plays an important role in deacetylation of acetylated
      amino acids and N-acetylated S-cysteine conjugates of halogenated alkenes and
      alkanes. AAIII, recently cloned from mouse kidney and partially characterized, is
      a mixture of tetramers and dimers. In the present work, AAIII dimers were
      purified and shown to be enzymatically active. Limited trypsinolysis showed two
      domains of approximately 9 and 25 kDa. The three-dimensional structure of the
      dimer was studied by electron microscopy of negative stained samples and by
      single-particle reconstruction. A 16A resolution model of the AAIII dimer was
      created. It has an unusual, cage-like, structure. A realistic AAIII tetramer
      model was built from two dimers.

PMID- 17434494
TI  - A novel light- and heat-responsive regulation of the groE transcription in the
      absence of HrcA or CIRCE in cyanobacteria.
AB  - The inactivation of the hrcA gene resulted in de-repression of the two CIRCE
      containing groE genes in a cyanobacterium Synechocystis sp. strain PCC6803,
      indicating that the CIRCE operator/HrcA repressor system operates in the
      cyanobacterium. We found that the groE expression in the hrcA mutant is greatly
      induced by heat and/or light. Removal of a K-box containing and an N-box
      containing region upstream of the groESL1 promoter abolished light-induced
      transcription of a luxAB reporter gene fused with the groESL1 promoter. Similar
      sequences to the K-box, GTTCGG-NNAN-CCNNAC, were also found upstream of the dnaK2
      genes. A specific binding of a protein(s) to the N-box, GATCTA, was detected by a
      gel mobility shift assay with using cell extracts. We propose that the
      cyanobacterial groEL expression is regulated by a putative positive mechanism
      mediated by these novel elements in addition to the HrcA/CIRCE system. The groEL2
      genes from Synechococcus sp. strain PCC 7942 and Thermosynechococcus elongatus,
      which lack CIRCE, K-box, and N-box naturally, were also induced by heat and/or
      light, indicating that the control mechanism of the unique light-responsive groE
      expression is highly diversified in cyanobacteria.

PMID- 17434495
TI  - Dissecting subsecond cadherin bound states reveals an efficient way for cells to
      achieve ultrafast probing of their environment.
AB  - Cells continuously probe their environment with membrane receptors, achieving
      subsecond adaptation of their behaviour [Diez, G., Gerisch, G., Anderson, K.,
      Muller-Taubenberger, A. and Bretschneider, T. (2006) Subsecond reorganization of
      the actin network in cell motility and chemotaxis. Proc. Natl. Acad. Sci. USA
      102, 7601-7606, Shamri, R., Grabovsky, V., Gauguet, J.M., Feigelson, S.,
      Manevich, E., Kolanus, W., Robinson, M.K., Staunton, D.E., von Andrian, U.H. and
      Alon, R. (2005) Lymphocyte arrest requires instantaneous induction of an extended
      LFA-1 conformation mediated by endothelium-bound chemokines. Nat. Immunol. 6, 497
      606, Jiang, G., Huang, A.H., Cai, Y., Tanase, M. and Sheetz, M.P. (2006) Rigidity
      sensing at the leading edge through alpha(V)beta(3) integrins and RPTPalpha.
      Biophys. J. 90, 1804-2006]. Recently, several receptors, including cadherins,
      were found to bind ligands with a lifetime of order of one second. Here we show
      at the single molecule level that homotypic C-cadherin association involves
      transient intermediates lasting less than a few tens of milliseconds. Further,
      these intermediates transitionned towards more stable states with a kinetic rate
      displaying exponential decrease with piconewton forces. These features enable
      cells to detect ligands or measure surrounding mechanical behaviour within a
      fraction of a second, much more rapidly than was previously thought.

PMID- 17434496
TI  - Design and switch of catalytic activity with the DNAzyme-RNAzyme combination.
AB  - Design and switch of catalytic activity in enzymology remains a subject of
      intense investigation. Here, we employ a DNAzyme-RNAzyme combination strategy for
      construction of a 10-23 deoxyribozyme-hammerhead ribozyme combination that
      targets different sites of the beta-lactamase mRNA. The 10-23 deoxyribozyme
      hammerhead ribozyme combination gene was cloned into phagemid vector pBlue
      scriptIIKS (+). In vitro the single-strand recombinant phagemid vector containing
      the combination sequence exhibited 10-23 deoxyribozyme activity, and the linear
      transcript displayed hammerhead ribozyme activity. In bacteria, the 10-23
      deoxyribozyme-hammerhead ribozyme combination inhibited the beta-lactamase
      expression and repressed the growth of drug-resistant bacteria. Thus, we created
      a DNAzyme-RNAzyme combination strategy that provides a useful approach to design
      and switch of catalytic activities for nucleic acid enzymes.

PMID- 17434497
TI  - Kinetic analysis of demetalation of bacteriochlorophyll c and e homologs purified
      from green sulfur photosynthetic bacteria.
AB  - Substituent-dependent demetalation kinetics of natural bacteriochlorophyll (BChl)
      c and e homologs purified from two green sulfur photosynthetic bacteria was first
      studied. Separated BChl e homologs, which possessed a formyl group at the 7
      position of their chlorin macrocycles, exhibited a significantly slow removal of
      central magnesium to free-base bacteriopheophytins in acidic aqueous acetone
      compared with the corresponding BChl c homologs, which possessed a methyl group
      at the 7-position. Additional methyl groups at the 8(2)-position of both BChl c
      and e molecules had little effect on the demetalation kinetics.

PMID- 17434498
TI  - Epididymal P34H protein deficiency in men evaluated for infertility.
AB  - Our study aimed to compare the frequency of epididymal protein P34H deficiency in
      a population of men undergoing routine infertility evaluation with that in men
      with proven fertility. Our results suggest that a significant proportion of men
      investigated for male infertility may be epididymal protein P34H deficient.

PMID- 17434499
TI  - First trimester bacterial vaginosis, individual microorganism levels, and risk of
      second trimester pregnancy loss among urban women.
AB  - OBJECTIVE: To examine the role of first trimester bacterial vaginosis (BV) and
      level of BV-associated microorganisms, diagnosed using the Nugent gram stain
      criteria and the risk of second trimester pregnancy loss among urban women.
      DESIGN: Prospective cohort study. SETTING: Urban prenatal care clinics.
      PATIENT(S): Women presenting for their first prenatal care visit who had
      completed 12 weeks gestation or less and resided within Philadelphia,
      Pennsylvania. MAIN OUTCOME MEASURE(S): Pregnancy loss. RESULT(S): Of 1948 women
      enrolled at a mean gestational age of 10 weeks (range 7.4 to 12.6 weeks), those
      with the highest level of BV-related vaginal flora alteration compared with women
      with normal vaginal flora had over a twofold increased risk of second trimester
      pregnancy loss after adjustment for confounders (adjusted hazard ratio [aHR]
      2.49, 95% confidence interval [CI] 1.13 to 5.48). Low Lactobacillus spp. and the
      absence of Lactobacillus spp. were also significantly related to the risk of
      second trimester pregnancy loss (aHR 1.32, 95% CI 1.10-1.64; aHR 2.30, 95% CI
      1.09-4.85; respectively). CONCLUSION(S): Overall BV positivity was not related to
      second trimester pregnancy loss. Comparing the highest to lowest tertile of BV
      positivity in early pregnancy conferred a two-fold increased risk of second
      trimester pregnancy loss and low amounts or the absence of Lactobacillus spp. in
      the first trimester also significantly increased the risk of second trimester
      pregnancy loss.

PMID- 17434500
TI  - Endometrial thickness and pregnancy outcome after intrauterine insemination.
AB  - OBJECTIVES: To investigate whether endometrial thickness on the day of hCG
      administration is a predictor of intrauterine insemination (IUI) success. DESIGN:
      A retrospective study. PATIENT(S): Two hundred forty-nine women undergoing IUI
      cycles. SETTING: University hospital-based infertility center. INTERVENTION(S):
      Endometrial thickness on the day of hCG administration, cycle parameters, and
      sperm quality were compared between pregnant and nonpregnant patients. A similar
      comparison was made between ongoing pregnancies and those that resulted in a
      loss. MAIN OUTCOME MEASURE(S): Endometrial thickness versus IUI outcome.
      RESULT(S): The overall pregnancy rate was 15%. Mean (+/- standard deviation)
      endometrial thickness on the day of hCG administration was significantly greater
      in cycles where pregnancy was achieved (10.1 +/- 3.0 vs. 7.7 +/- 3.5). In the
      univariate analysis, the following variables affected the pregnancy rate: the
      woman's age, duration of infertility, the number of IUI cycles, the number of
      follicles, the diameter of the dominant follicle, the duration of follicle
      maturation, and sperm count, motility, and morphology. In the multivariate
      analysis, the strongest predictor of IUI success was the number of IUI cycles.
      The woman's age was negatively associated with pregnancy outcome, while
      endometrial thickness and the total motile sperm count were positively associated
      with pregnancy outcome. CONCLUSION(S): The results of the present study suggest
      that clinicians providing IUI for infertile couples must pay close attention to
      endometrial development as well as to follicle growth and sperm motility.

PMID- 17434501
TI  - Differential effects of aging on activin A and its binding protein, follistatin,
      across the menopause transition.
AB  - To assess the involvement of ovarian-derived regulatory proteins in FSH
      modulation, we compared FSH, inhibin A, inhibin B, activin A, and follistatin
      (FS) in 79 women from the following five groups: young cycling, older cycling,
      perimenopause (PERI), spontaneous menopause (PM), and surgical menopause
      receiving estrogen (OVX+ET). Although inhibin B varied as expected by ovarian
      function, no group differences were observed in activin A, barring a tendency for
      an increase in PERI, while FS 288 was lower in the PERI, PM, and OVX+ET groups
      and negatively correlated with advancing age.

PMID- 17434502
TI  - High risk of temporary alteration of semen parameters after recent acute febrile
      illness.
AB  - OBJECTIVE: To report parameters in semen samples and sperm deoxyribonucleic acid
      integrity in a fertile volunteer presenting a 2-day fever of 39 degrees -40
      degrees C. DESIGN: Case report. SETTING: University-affiliated teaching hospital.
      INTERVENTION(S): None. PATIENT(S): Semen samples from a fertile volunteer of
      proven fertility were obtained and analyzed before the febrile illness episode
      and at days 15, 37, 58, 79, and >180 after the fever. MAIN OUTCOME MEASURE(S):
      Semen parameters (total sperm count, motility a+b, and vitality), sperm
      protamination state, measured by sperm chromatin structure assay (SCSA) and
      apoptotic activities, measured by terminal uridine nick-end labeling (TUNEL)
      assay. RESULTS: Total sperm count significantly decreased at days 15, 37, and 58
      after the fever and returned to normal by day 79 after the fever. The percentage
      of motility significantly decreased at days 15 and 37 after the fever and
      returned to normal by day 58. Vitality score also showed a slight, although not
      statistically significant, decrease after the fever. The DNA fragmentation index
      (DFI, a SCSA parameter), which defines abnormal chromatin structure,
      significantly increased by 24% and 36% at days 15 and 37 after the fever,
      respectively, and decreased to 15% and 8% when reaching days 58 and 79 after the
      fever. High DNA stainability (HDS, a SCSA parameter) also significantly increased
      at day 37 after the fever. On the other hand, sperm DNA fragmentation, as
      measured by TUNEL assay, increased up to 23% by day 15 after the fever but this
      was not statistically significant. CONCLUSION(S): This report demonstrates that a
      febrile episode can have marked effects on semen parameters and sperm DNA
      integrity. These results are particularly important for the counseling of
      infertile couples and in relation to assisted reproductive techniques (ART).

PMID- 17434503
TI  - Recombinant follicle-stimulating hormone (rFSH) supplemented with low-dose human
      chorionic gonadotropin compared with rFSH alone for ovarian stimulation for in
      vitro fertilization.
AB  - Low-dose hCG supplementation was administered at the start of ovarian
      stimulation, concomitantly with recombinant FSH (rFSH) in GnRH antagonist cycles,
      and these were compared with GnRH-a cycles that used rFSH alone. The low-dose hCG
      group had similar implantation and pregnancy rates but had significantly reduced
      rFSH requirements, allowing for an average cost savings of $600 per cycle.

PMID- 17434504
TI  - Establishment of ovarian reserve: a quantitative morphometric study of the
      developing human ovary.
AB  - OBJECTIVE: To assess directly the dynamics of the formation of the ovarian
      reserve in the normal human ovary by evaluating the total number of follicles in
      developing ovaries when folliculogenesis occurs. DESIGN: Histomorphometry-based
      follicle counts in complete serial tissue sections. SETTING: Functional Anatomy
      Research Center, University of Milano. PATIENT(S): Thirteen fetuses, neonates,
      and one 8-month-old infant. INTERVENTION(S): Fifteen ovaries were completely cut,
      obtaining serial sections. Ovarian volume, volume fractions, density and total
      number of follicles per ovary were calculated using quantitative morphometric
      methods. MAIN OUTCOME MEASURE(S): Age-related dynamics of the establishment of
      ovarian reserve in human developing ovary at the end of the organogenesis.
      RESULT(S): The ovarian reserve (100,000 follicles at 15 weeks of postconceptional
      age) increased progressively to 680,000 follicles at 34 weeks. At 8 months of
      postnatal age the pool was still about 680,000 primordial follicles.
      CONCLUSION(S): The consistence of the primordial follicle pool during
      organogenesis shows an exponential increase until month 8 of prenatal life and it
      is subsequently maintained without modifications at least until month 8 of
      postnatal life.

PMID- 17434505
TI  - A multicenter randomized, controlled study comparing laparoscopic versus
      minilaparotomic myomectomy: reproductive outcomes.
AB  - OBJECTIVE: To assess the reproductive outcomes after minilaparotomic and
      laparoscopic myomectomy in patients wishing to conceive. DESIGN: Randomized
      controlled trial. SETTING: Departments of obstetrics and gynecology of the
      universities of Catanzaro, Rome, and Florence, Italy. PATIENT(S): One hundred
      thirty-six women with symptomatic uterine leiomyomas or unexplained infertility.
      INTERVENTION(S): Laparoscopic and minilaparotomic myomectomy. MAIN OUTCOME
      MEASURE(S): Pregnancy, abortion, and live-birth rates. RESULT(S): Between the
      laparoscopic and minilaparotomic groups no difference was observed in cumulative
      pregnancy, live-birth, and abortion rates, whereas pregnancy and live-birth rates
      per cycle, and time to first pregnancy and live-birth were significantly higher
      in the laparoscopic than in the minilaparotomic group. Categorizing the patients
      according to surgical indication for myomectomy, cumulative pregnancy rate,
      pregnancy, and live-birth rates per cycle, and time to first pregnancy and live
      birth were significantly better after laparoscopic myomectomy in symptomatic
      patients, whereas all reproductive outcomes were similar between the two groups
      in patients with unexplained infertility. CONCLUSION(S): Minilaparotomic and
      laparoscopic myomectomy improves in a similar manner the reproductive outcomes in
      patients with unexplained infertility, whereas the laparoscopic approach provides
      the best benefits in fertile patients with symptomatic leiomyomas.

PMID- 17434506
TI  - Massive ascites and hydrothorax after leuprolide acetate administration in a down
      regulated woman undergoing assisted reproduction.
AB  - OBJECTIVE: To present an atypical case of massive ascites and hydrothorax after
      leuprolide acetate administration in a down-regulated woman undergoing assisted
      reproduction. DESIGN: Case report. SETTING: Centre for Reproductive Medicine,
      Department of Obstetrics, Gynaecology, and Neonatology, University of Parma,
      Parma, Italy. PATIENT(S): A 41-year-old, nulliparous, white woman who developed
      massive ascites and hydrothorax after administration of 0.50 mg/day of
      subcutaneous leuprolide acetate, beginning at the midluteal phase.
      INTERVENTION(S): Down-regulation with the gonadotropin-releasing hormone analogue
      was discontinued, and therapy was started with furosemide 50 mg/day for 10 days.
      MAIN OUTCOME MEASURE(S): Successful medical reduction of ascites and hydrothorax.
      RESULT(S): Resolution of symptoms. CONCLUSION(S): A comprehensive MEDLINE search
      revealed this to be the first reported case of massive ascites and hydrothorax
      after leuprolide acetate administration (0.5 mg daily) in a down-regulated woman
      undergoing assisted reproduction. This case can be explained by an increase in
      capillary permeability, which resulted in a rapid fluid shift from the
      intravascular space into the third space. We believe that ascites in our patient
      resulted from an increase in estradiol in the ovaries, due to a direct action of
      the gonadotropin-releasing hormone analogue on the corresponding ovarian
      receptors in the first few days after the start of therapy.

PMID- 17434507
TI  - Male fertility and protein C inhibitor/plasminogen activator inhibitor-3 (PCI):
      localization of PCI in mouse testis and failure of single plasminogen activator
      knockout to restore spermatogenesis in PCI-deficient mice.
AB  - OBJECTIVE: To investigate the mechanisms responsible for the testicular
      abnormalities and infertility of previously generated male protein C inhibitor
      (PCI)-deficient mice. DESIGN: Determination of the localization of PCI in the
      reproductive organs of wild-type males. Generation of double knockout mice
      lacking the protease inhibitor PCI and one plasminogen activator, either
      urokinase (uPA) or tissue plasminogen activator (tPA), both of which are PCI
      target proteases. SETTING: Animal research and histologic analysis. ANIMAL(S):
      Male mice of desired genotype. INTERVENTION(S): Fertility testing of double
      knockout mice. MAIN OUTCOME MEASURE(S): Infertility of PCI(-/-)uPA(-/-) and PCI(
      /-)tPA(-/-) double knockout mice. RESULT(S): In the testes of wild-type males PCI
      was detected in spermatocytes of prophase I, as well as in late spermatids and
      mature spermatozoa, but absent from somatic cells. All PCI(-/-) uPA(-/-) and PCI(
      /-) tPA(-/-) male mice were infertile and histologic analysis of testis showed
      similar alterations as previously described for PCI(-/-) mice. CONCLUSION(S): The
      abnormal spermatogenesis of PCI (plasminogen activator inhibitor-3)-deficient
      mice cannot be rescued by single plasminogen activator knockout.

PMID- 17434508
TI  - Reassessing the value of varicocelectomy as a treatment for male subfertility
      with a new meta-analysis.
AB  - OBJECTIVE: To determine the efficacy of varicocelectomy as a treatment for male
      factor infertility by improving the chance of spontaneous pregnancy. DESIGN: Meta
      analysis. SETTING: Cleveland Clinic's Glickman Urological Institute. PATIENT(S):
      Infertile men with abnormal results on semen analyses and a palpable varicocele.
      INTERVENTION(S): Surgical varicocelectomy. MAIN OUTCOME MEASURE(S): Spontaneous
      pregnancy outcome. RESULT(S): The odds of spontaneous pregnancy after surgical
      varicocelectomy, compared with no or medical treatment for palpable varicocele,
      were 2.87 (95% confidence interval [CI], 1.33-6.20) with use of a random-effects
      model or 2.63 (95% CI, 1.60-4.33) with use of a fixed-effects model. The number
      needed to treat was 5.7 (95% CI, 4.4-9.5). CONCLUSION(S): Surgical
      varicocelectomy in infertile men with palpable lesions and at least one abnormal
      semen parameter improves the odds of spontaneous pregnancy in their female
      partners. Five studies were included (two randomized, three observational). All
      were scored for bias. Our study suggests that varicocelectomy in selected
      patients does indeed have beneficial effects on fertility status.

PMID- 17434509
TI  - Characteristics of the urinary luteinizing hormone surge in young ovulatory
      women.
AB  - OBJECTIVE: To define characteristics of the luteinizing hormone (LH) surge in
      urine. DESIGN: Observational study. SETTING: Academic center. PATIENT(S): 46
      women aged 20 to 35 years with regular menstrual cycles. INTERVENTION(S):
      Collected first morning urine daily, throughout one menstrual cycle. MAIN OUTCOME
      MEASURE(S): Urinary LH, follicle-stimulating hormone (FSH), estrone conjugate
      (E1C), and pregnanediol-3-glucuronide (PDG). RESULT(S): Three women lacked LH
      surges. Mean LH surge: start = day 14.5 (+/-3.6 SD) (range: 9-26); peak = 41.2
      mIU/mg creatinine (+/-20 SD) (range: 12.1-104.0); fold increase = 7.7 (+/-3.0 SD)
      (range: 2.5-14.8); duration = 7.6 days (+/-1.5 SD) (range: 5-11). The onset of LH
      surge was of two types: rapid onset (within 1 day) (42.9%) or gradual onset (2 to
      6 days) (57.1%). Configurations of LH surges were of three types: spike (41.9%),
      biphasic (44.2%), or plateau (13.9%). All LH surges demonstrated a gradual
      decrease to baseline. Three women (7%) did not have FSH rises coincident with LH
      surges. All displayed E1C rises during the middle to late follicular phase.
      CONCLUSION(S): The LH surges that result in ovulation are extremely variable in
      configuration, amplitude, and duration. The FSH rise does not seem essential for
      ovulation. However, an E1C rise occurred in all cycles, confirming the critical
      role of estrogen in induction of the LH surge.

PMID- 17434510
TI  - Ectopic pregnancy rates with frozen compared with fresh blastocyst transfer.
AB  - OBJECTIVE: To compare the rate of ectopic pregnancy (EP) with fresh versus frozen
      blastocyst transfer in our program during the same time period. DESIGN:
      Retrospective analysis. SETTING: University IVF program. PATIENT(S): Women who
      achieved a clinical pregnancy after IVF between 1998 and 2005. INTERVENTION(S):
      In our program, cryopreservation is performed at the blastocyst stage. Embryo
      transfer was performed 1 to 1.5 cm short of the fundus by abdominal ultrasound
      guidance. MAIN OUTCOME MEASURE(S): The incidence of EP was examined in relation
      to fresh versus frozen blastocyst transfer. RESULT(S): In the frozen blastocyst
      group, there were 5 EPs out of 180 clinical pregnancies (2.8%), and there were 10
      EPs out of 564 clinical pregnancies (1.8%) in the fresh blastocyst group.
      CONCLUSION(S): The rate of EP is not significantly increased after the transfer
      of frozen thawed blastocysts compared with fresh blastocyst transfer.

PMID- 17434511
TI  - Hormonal suppression treatment or dietary therapy versus placebo in the control
      of painful symptoms after conservative surgery for endometriosis stage III-IV. A
      randomized comparative trial.
AB  - OBJECTIVE: To evaluate the effectiveness for the outcomes of endometriosis
      related pain and quality of life of conservative surgery plus placebo compared
      with conservative surgery plus hormonal suppression treatment or dietary therapy.
      DESIGN: Randomized comparative trial. SETTING: University hospital. PATIENT(S):
      Two hundred twenty-two consecutive women who underwent conservative pelvic
      surgery for symptomatic endometriosis stage III-IV (r-AFS). INTERVENTION(S): Six
      months of placebo (n = 110) versus GnRH-a (tryptorelin or leuprorelin, 3.75 mg
      every 28 days) (n = 39) or continuous estroprogestin (ethynilestradiol, 0.03 mg
      plus gestoden, 0.75 mg) (n = 38) versus dietary therapy (vitamins, minerals
      salts, lactic ferments, fish oil) (n = 35). MAIN OUTCOME MEASURE(S): Painful
      symptoms (visual analogue scale score) and quality-of-life endometriosis-related
      symptoms (SF-36 score) at 12 months' follow-up. RESULT(S): Patients treated with
      postoperative hormonal suppression therapy showed less visual analogue scale
      scores for dysmenorrhoea than patients of the other groups. Hormonal suppression
      therapy and dietary supplementation were equally effective in reducing
      nonmenstrual pelvic pain. Surgery plus placebo showed significative decrease in
      dyspareunia scores. Postoperative medical and dietary therapy allowed a better
      quality of life than placebo. CONCLUSION(S): Postoperative hormonal suppression
      treatment or dietary therapy are more effective than surgery plus placebo to
      obtain relief of pain associated with endometriosis stage III-IV and improvement
      of quality of life.

PMID- 17434512
TI  - Light intensity and wavelength during embryo manipulation are important factors
      for maintaining viability of preimplantation embryos in vitro.
AB  - OBJECTIVE: To optimize embryo culture system by evaluating lighting effect during
      in vitro manipulation. DESIGN: Randomized prospective study using an animal
      model. SETTING: Gamete and Stem Cell Biotechnology Laboratory at Seoul National
      University in Korea. ANIMAL(S): Twelve- to 15-week-old hamsters (Mesocricetus
      auratus). INTERVENTION(S): Two-cell embryos were manipulated in vitro under
      lighting of different intensities and wavelengths. MAIN OUTCOME MEASURE(S):
      Preimplantation development, Hsp70 expression, reactive oxygen species (ROS)
      generation, and blastomere apoptosis. RESULT(S): A significant increase in morula
      and blastocyst formation was detected at 200 lux compared with 900 lux visible
      ray lighting, but not compared with 500 lux. At 200-lux lighting, red (620-750
      nm) ray yielded the best development, whereas blue (445-500 nm) decreased
      blastocyst formation. Compared with the visible ray, Hsp70 expression and ROS
      generation in morula were increased in the blue ray but decreased in the red ray
      lighting. The blue ray also reduced blastocyst quality with increasing blastomere
      apoptosis. CONCLUSION(S): Specific wavelength of visible ray increases Hsp70
      expression, ROS generation, and blastomere apoptosis. Therefore, removing this
      stress factor improves embryo development.

PMID- 17434513
TI  - Mutations of SYCP3 are rare in infertile Spanish men with meiotic arrest.
AB  - No functional SYCP3 exonic SNP was found in infertile Spanish patients with
      meiosis arrest, suggesting that SYCP3 mutations very likely are not relevant in
      Spain in genetic susceptibility to meiosis arrest, just as in other studied
      European populations.

PMID- 17434514
TI  - Elevated expression of P450c17 (CYP17) during testicular formation in the frog.
AB  - Sex steroids play decisive roles in gonadal differentiation in many species of
      vertebrates. The sex can be changed by sex steroids in some species of
      amphibians, but the mechanism of the sex-reversal is largely unknown. In this
      study, we cloned and characterized 3 cDNAs encoding sex steroid-synthesizing
      enzymes, i.e., CYP11A1, CYP17 and 3beta-HSD from the frog Rana rugosa. RT-PCR
      analysis showed that the CYP17 expression was much higher in male gonads than in
      female ones during sex determination in R. rugosa, whereas CYP11A1 and 3beta-HSD
      showed no sexually dimorphic expression. When testosterone was injected into
      tadpoles for female-to-male sex reversal, CYP17 expression appeared to be very
      strong in the gonad at days 16 and 24 after injection of testosterone. CYP11A1
      was also transcribed higher at day 16, but its expression was weaker when
      compared with that of CYP17. The expression of 3beta-HSD did not change during
      the sex reversal. In addition, in situ hybridization analysis revealed that CYP17
      was expressed in somatic cells of the indifferent male gonad and in those of the
      testis. Positive signals of CYP17 were also produced in somatic cells of a female
      to-male sex-reversed gonad (testis) at days 16 and 24 post testosterone
      injection, but not in the ovary. Taken together, the results suggest that CYP17
      is very involved in testicular differentiation of the gonad in R. rugosa.

PMID- 17434515
TI  - Melatonin synthesis under calcium constraint in gilthead sea bream (Sparus
      auratus L.).
AB  - Brain or blood plasma melatonin was analysed as a measure for pineal melatonin
      production in sea bream. Access to calcium was limited by diluting the seawater
      to 2.5 per thousand and removing calcium from the diet or by prolonged feeding of
      vitamin D-deficient diet. Interactions/relations between melatonin and calcium
      balance and the hypercalcemic endocrines PTHrP and calcitriol were assessed.
      Restricting calcium availability in both water and diet had no effect on plasma
      melatonin, but when calcium was low in the water or absent from food, increased
      and decreased plasma melatonin was observed, respectively. Fish on a vitamin D
      deficient diet (D- fish) showed decreased plasma calcitriol levels and remained
      normocalcemic. Decreased brain melatonin was found at all sampling times (10-22
      weeks) in the D- fish compared to the controls. A positive correlation between
      plasma Ca2+ and plasma melatonin was found (R(2)=0.19; N=41; P <0.01) and brain
      melatonin was negatively correlated with plasma PTHrP (R(2)=0.78; N=4; P <0.05).
      The positive correlation between plasma levels of melatonin and Ca2+ provides
      evidence that melatonin synthesis is influenced by plasma Ca2+. The decreased
      melatonin production in the D- fish points to direct or indirect involvement of
      calcitriol in melatonin synthesis by the pineal organ in teleosts. The
      hypercalcemic factors PTHrP and calcitriol appeared to be negatively correlated
      with melatonin and this substantiates an involvement of melatonin in modulating
      the endocrine response to cope with hypocalcemia. It further points to the
      importance of Ca2+ in melatonin physiology.

PMID- 17434516
TI  - Precision coordinated control of multi-axis gantry stages.
AB  - High precision motion control of gantry stages has found numerous applications in
      the manufacturing industries where precise positioning is crucial. This paper
      presents a survey of existing control schemes as well as the development of
      enhanced schemes for the coordinated motion control of moving gantry stages. In
      particular, a robust control scheme is proposed which uses a feedback controller
      with a sliding mode to correct for the tracking error and to coordinate multiple
      axis to move in tandem. Simulation and experimental results will illustrate and
      compare the performance of the control schemes presented in the paper.

PMID- 17434517
TI  - Laparoscopic myomectomy for large intramural and submucous fibroids.

PMID- 17434518
TI  - Sacculogenesis of Buddenbrockia plumatellae (Myxozoa) within the invertebrate
      host Plumatella repens (Bryozoa) with comments on the evolutionary relationships
      of the Myxozoa.
AB  - Members of the phylum Myxozoa are obligate parasites, primarily of aquatic
      organisms. Their phylogeny has remained problematic, with studies placing them
      within either the Bilateria or Cnidaria. The discovery that the enigmatic
      Buddenbrockia plumatellae is a myxozoan that possesses distinct bilaterian
      features appeared to have finally resolved the debate. B. plumatellae is
      described as a triploblastic 'worm-like' organism, within which typical myxozoan
      malacospores form. Using EM we examined the early development of the B.
      plumatellae 'worms' within the bryozoan host Plumatella repens. The initial
      development involved numerous unicellular, amoeboid pre-saccular stages that were
      present within the basal lamina of the host's body wall. These stages migrate
      immediately beneath the peritoneum where a significant host tissue reaction
      occurs. The stages aggregate, initiating the formation of a 'worm'. The base of a
      developing 'worm' forms a pseudosyncytium which resolves into an ectoderm
      surrounding a mesendoderm. The pseudosyncytium is directly anchored into
      neighbouring host cells via masses of striated fibres. The replication of the
      ectodermal and mesendodermal cells extends the developing 'worm' into the coelom
      of the host. The mesendoderm resolves to form a mesoderm and an endoderm.
      Myogenesis appears to be initiated from the anchored end of the 'worm' and
      develops along the mesoderm. The aggregation and differentiation of amoeboid pre
      saccular stages to initiate the 'worm' draws analogies to the sacculogenesis
      observed for Tetracapsuloides bryosalmonae, B. plumatellae's sister taxon within
      the class Malacosporea. The development of a multicellular, spore forming
      organism, from single cells does not correlate to any bilaterian or cnidarian
      species. Current phylogenies indicate the Myxozoa are basal bilaterians along
      with the Acoela and Mesozoa. Comparison with these other basal groups may help to
      resolve the placement of Myxozoa within the tree of life.

PMID- 17434519
TI  - Knee model sensitivity to cruciate ligaments parameters: a stability simulation
      study for a living subject.
AB  - If the biomechanic function of the different anatomical sub-structures of the
      knee joint was needed in physiological conditions, the only possible way is a
      modelling approach. Subject-specific geometries and kinematic data, acquired from
      the same living subject, were the foundations of the 3D quasi-static knee model
      developed. Each cruciate ligament was modelled by means of 25 elastic springs,
      paying attention to the anatomical twisting of the fibres. The sensitivity of the
      model to the cross-sectional area was performed during the anterior/posterior
      tibial translations, the sensitivity to all the cruciate ligaments parameters was
      performed during the internal/external rotations. The model reproduced very well
      the mechanical behaviour reported in literature during anterior/posterior
      translations, in particular considering 30% of the mean insertional area. During
      the internal/external tibial rotations, similar behaviour of the axial torques
      was obtained in the three sensitivity analyses. The overlapping of the ligaments
      was assessed at about 25 degrees of internal axial rotation. The presented model
      featured a good level of accuracy in combination with a low computational weight,
      and it could provide an in vivo estimation of the role of the cruciate ligaments
      during the execution of daily living activities.

PMID- 17434520
TI  - The role of muscles in joint degeneration and osteoarthritis.
AB  - The purpose of this work was to establish a controlled and reversible muscle
      weakness model for studying the effects of weakness on joint degeneration leading
      to osteoarthritis (OA). The knee extensor muscles of rabbits were injected with
      single or repeat doses of Botulinum type-A toxin (BTX-A) to partially inhibit
      acetylcholine (ACh) release at the neuromuscular junction. BTX-A-injected muscles
      atrophied, they became weaker and push-off forces during hopping were reduced
      compared to control. BTX-A injections had the greatest effect at short-muscle
      length and low-stimulation frequencies. Superimposing BTX-A injections on
      anterior cruciate ligament transection did not cause greater muscle atrophy or
      weakness than BTX-A injections alone. Monthly repeat injections could be used to
      keep muscles weak for half a year without any obvious adverse effects to the
      animals. Gross morphology of the knees and histology of articular cartilage
      suggested that, in some animals, 4 weeks of muscle weakness resulted in initial
      signs of joint degeneration, indicating that weakness may be an independent risk
      factor for joint degeneration leading to OA.

PMID- 17434521
TI  - Mesoscopic simulations of phase distribution effects on the effective thermal
      conductivity of microgranular porous media.
AB  - This paper analyzes the phase distribution effects on the effective thermal
      conductivity (ETC) of multi-phase microgranular porous media using mesoscopic
      statistics based numerical methods. A multi-parameter random generation-growth
      method, quartet structure generation set (QSGS), is developed for replicating
      microstructures of multi-phase granular porous media based on the macroscopic
      statistical information, such as the volume fractions and the phase interactions.
      The phase distribution characteristics and the interphase connections are
      controlled by adjusting the related parameters. Then the energy transport
      equations through porous media are solved by a lattice Boltzmann method developed
      by us with multi-phase conjugate heat transfer considered. The results indicate
      that a smaller average particle size could lead to a larger effective thermal
      conductivity of two-phase porous media for a certain porosity. For the
      anisotropic media, if the larger directional growth probability is along the
      direction of temperature gradient, the effective thermal conductivity in the
      parallel direction is enhanced as a result, and that in the vertical direction
      will be weakened. For multi-phase porous media, the degree of phase
      conglomeration is determined by the phase interactions. A larger liquid-liquid
      interaction leads to a higher degree of liquid phase conglomeration and therefore
      a larger effective thermal conductivity of the porous media.

PMID- 17434522
TI  - The aqueous catanionic system sodium perfluorooctanoate-dodecyltrimethylammonium
      bromide at low concentration.
AB  - The interaction between sodium perfluorooctanoate (SPFO) and
      dodecyltrimethylammonium bromide (DTAB) was studied by several methods and it was
      found strongly synergistic. Above a mole fraction of SPFO in the surfactant
      mixture (alpha(SPFO))=0.38, the interaction is repulsive and increases with the
      content of SPFO in both, the overall mixture and micelles, whereas the
      interaction is attractive if DTAB is in excess. At alpha(SPFO)=0.38 the low
      miscibility between hydrocarbon and fluorocarbon is counterbalanced by the
      electrostatic attraction between the opposite charged head groups, and the
      micelle composition is ideal (i.e., the mole fraction of SPFO in micelles
      X(SPFO)=alpha(SPFO)=0.38). The solubility of fluorocarbon in hydrocarbon is lower
      than that of hydrocarbon in fluorocarbon. Micelles of DTAB act as a solvent for
      SPFO without important structural changes, whilst micelles of SPFO undergo
      important changes when dissolve DTAB. This asymmetry may be interpreted as caused
      by the difference in chain length that favors the inclusion of the shorter chain
      in micelles of the longer surfactant, but disfavors the opposite process. Above
      X(SPFO)=0.5 there is an excess adsorption of bromide ions on the mixed micelles
      surface, giving rise to a high zeta potential. Micelles of pure SPFO or pure DTAB
      show an important energy barrier which prevents micelle flocculation. The
      inclusion of SPFO in DTAB micelles produces a reduction of the energy barrier,
      which disappeared when alpha(SPFO)=0.5. This produces the flocculation of
      micelles giving rise to the formation of a non-birefringent coacervate, which is
      probably formed by unordered isometric clusters of micelles.

PMID- 17434523
TI  - Susceptibility of the filbertworm (Cydia latiferreana, Lepidoptera: Tortricidae)
      and filbert weevil (Curculio occidentalis, Coleoptera: Curculionidae) to
      entomopathogenic nematodes.
AB  - The objective of this study was to determine the susceptibility of the two
      primary direct insect pests of hazelnuts in Oregon to three species of
      entomopathogenic nematodes. The entomopathogenic nematodes (Heterorhabditis
      marelatus Pt. Reyes, Steinernema carpocapsae All and Steinernema kraussei L137)
      were used in laboratory soil bioassays to determine their virulence against
      filbertworm, Cydia latiferreana (Walsingham) (Lepidoptera: Tortricidae) and
      filbert weevil, Curculio occidentalis (Casey) (Coleoptera: Curculionidae). All
      three nematode species were infective in laboratory bioassays. Infectivity ranged
      from 73-100% and 23-85% for filbertworm and filbert weevil, respectively. Field
      results were similar to those found in the laboratory with filbertworm larvae
      being more susceptible to nematode infection.

PMID- 17434524
TI  - S-nitrosylation and PEGylation of hemoglobin: toward a blood substitute that
      recapitulates blood.

PMID- 17434525
TI  - Nucleotide substrate recognition by UDP-N-acetylglucosamine acyltransferase
      (LpxA) in the first step of lipid A biosynthesis.
AB  - Lipid A is an integral component of the lipopolysaccharide (LPS) that forms the
      selective and protective outer monolayer of Gram-negative bacteria, and is
      essential for bacterial growth and viability. UDP-N-acetylglucosamine
      acyltransferase (LpxA) initiates lipid A biosynthesis by catalyzing the transfer
      of R-3-hydroxymyristic acid from acyl carrier protein to the 3'-hydroxyl group of
      UDP-GlcNAc. The enzyme is a homotrimer, and previous studies suggested that the
      active site lies within a positively charged cleft formed at the subunit-subunit
      interface. The crystal structure of Escherichia coli LpxA in complex with UDP
      GlcNAc reveals details of the substrate-binding site, with prominent hydrophilic
      interactions between highly conserved clusters of residues (Asn198, Glu200,
      Arg204 and Arg205) with UDP, and (Asp74, His125, His144 and Gln161) with the
      GlcNAc moiety. These interactions serve to bind and orient the substrate for
      catalysis. The crystallographic model supports previous results, which suggest
      that acylation occurs via nucleophilic attack of deprotonated UDP-GlcNAc on the
      acyl donor in a general base-catalyzed mechanism involving a catalytic dyad of
      His125 and Asp126. His125, the general base, interacts with the 3'-hydroxyl group
      of UDP-GlcNAc to generate the nucleophile. The Asp126 side-chain accepts a
      hydrogen bond from His125 and helps orient the general base to participate in
      catalysis. Comparisons with an LpxA:peptide inhibitor complex indicate that the
      peptide competes with both nucleotide and acyl carrier protein substrates.

PMID- 17434527
TI  - A simple, RNA-mediated allosteric switch controls the pathway to formation of a
      T=3 viral capsid.
AB  - Using mass spectrometry we have detected both assembly intermediates and the
      final product, the T=3 viral capsid, during reassembly of the RNA bacteriophage
      MS2. Assembly is only efficient when both types of quasiequivalent coat protein
      dimer seen in the final capsid are present in solution. NMR experiments confirm
      that interconversion of these conformers is allosterically regulated by sequence
      specific binding of a short RNA stem-loop. Isotope pulse-chase experiments
      confirm that all intermediates observed are competent for further coat protein
      addition, i.e., they are all on the pathway to capsid formation, and that the
      unit of capsid growth is a coat protein dimer. The major intermediate species are
      dominated by stoichiometries derived from formation of the particle threefold
      axis, implying that there is a defined pathway toward the T=3 shell. These
      results provide the first experimental evidence for a detailed mechanistic
      explanation of the regulation of quasiequivalent capsid assembly. They suggest a
      direct role for the encapsidated RNA in assembly in vivo, which is consistent
      with the structure of the genomic RNA within wild-type phage.

PMID- 17434526
TI  - The novel fold of scytovirin reveals a new twist for antiviral entry inhibitors.
AB  - The solution structure of the potent 95 residue anti-HIV protein scytovirin has
      been determined and two carbohydrate-binding sites have been identified. This
      unique protein, containing five structurally important disulfide bonds,
      demonstrates a novel fold with no elements of extended regular secondary
      structure. Scytovirin contains two 39 residue sequence repeats, differing in only
      three amino acid residues, and each repeat has primary sequence similarity to
      chitin binding proteins. Both sequence repeats form similarly structured domains,
      with the exception of one region. The result is two carbohydrate-binding sites
      with substantially different affinities. The unusual fold clusters aromatic
      residues in both sites, suggesting a binding mechanism similar to other known
      hevein-like carbohydrate-binding proteins but differing in carbohydrate
      specificity. Scytovirin, originally isolated from the cyanobacterium Scytonema
      varium, holds potential as an HIV entry inhibitor for both therapeutic and
      prophylactic anti-HIV applications. The high-resolution structural studies
      reported are an important initial step in unlocking the therapeutic potential of
      scytovirin.

PMID- 17434528
TI  - Immunophysical exploration of C3d-CR2(CCP1-2) interaction using molecular
      dynamics and electrostatics.
AB  - The formation of the complex between the d-fragment of the complement component
      C3 (C3d) and the modular complement receptor-2 (CR2) is important for cross
      linking foreign antigens with surface-bound antibodies and C3d on the surface of
      B cells. The first two modules of CR2, complement control protein modules (CCPs),
      participate in non-bonded interactions with C3d. We have used computational
      methods to analyze the dynamic and electrostatic properties of the C3d-CR2(CCP1
      2) complex. The interaction between C3d and CR2 is known to depend on pH and
      ionic strength. Also, the intermodular mobility of the CR2 modules has been
      questioned before. We performed a 10 ns molecular dynamics simulation to generate
      a relaxed structure from crystal packing effects for the C3d-CR2(CCP1-2) complex
      and to study the energetics of the C3d-CR2(CCP1-2) association. The MD simulation
      suggests a tendency for intermodular twisting in CR2(CCP1-2). We propose a two
      step model for recognition and binding of C3d with CR2(CCP1-2), driven by long
      and short/medium-range electrostatic interactions. We have calculated the matrix
      of specific short/medium-range pairwise electrostatic free energies of
      interaction involved in binding and in intermodular communications. Electrostatic
      interactions may mediate allosteric effects important for C3d-CR2(CCP1-2)
      association. We present calculations for the pH and ionic strength-dependence of
      C3d-CR2(CCP1-2) ionization free energies, which are in overall agreement with
      experimental binding data. We show how comparison of the calculated and
      experimental data allows for the decomposition of the contributions of
      electrostatic from other effects in association. We critically compare predicted
      stabilities for several mutants of the C3d-CR2(CCP1-2) complex with the available
      experimental data for binding ability. Finally, we propose that CR2(CCP1-2) is
      capable of assuming a large array of intermodular topologies, ranging from closed
      V-shaped to open linear states, with similar recognition properties for C3d, but
      we cannot exclude an additional contact site with C3d.

PMID- 17434529
TI  - Sulfate acts as phosphate analog on the monomeric catalytic fragment of the CPx
      ATPase CopB from Sulfolobus solfataricus.
AB  - The crystal structure of the catalytic fragment of a Sulfolobus solfataricus P
      type ATPase, CopB-B, was determined with a 2.6 A resolution. CopB-B is the major
      soluble fragment of the archaeal CPx-ATPase CopB and is comprized of a nucleotide
      and a phosphorylation domain. In the crystalline state two molecules of CopB-B
      are in close contact to each other, although the presence of dimers in free
      solution could be ruled out by analytical ultracentrifugation. The overall
      architecture of CopB-B is similar to that of other P-type ATPases such as Ca
      ATPase. Short peptide segments are linking the nucleotide binding to the
      phosphorylation domain. CopB-B exhibits 33% sequence identity (of 216 aligned
      residues) with the respective fragment of the Archaeoglobus fulgidus ATPase CopA.
      The CopB-B nucleotide-binding domain has the most primitive fold yet identified
      for this enzyme class. It is 24% identical to the nucleotide-binding domain of
      the disease-related Wilson ATPase ATP7B (80 structurally aligned residues).
      Structural superposition with Ca-ATPase suggests a putative nucleotide-binding
      site in CopB-B. The phosphorylation domain of CopB-B is structurally related to
      the corresponding part of Ca-ATPase in the anion-bound E2 state. In CopB-B
      crystals, a bound sulfate anion was identified at the phosphate-binding location.
      In solution state, the potential binding of CopB-B to phosphate was probed with
      (32)P(i). Bound phosphate could be readily displaced by orthovanadate at
      submillimolar concentration as well as by sulfate at millimolar concentration. It
      is possible therefore to assign the structure of the sulfate-bound
      phosphorylation domain of CopB-B to a state related to the E2.P(i) intermediate
      state of the catalytic cycle.

PMID- 17434530
TI  - On itinerant water molecules and detectability of protein-protein interfaces
      through comparative analysis of homologues.
AB  - We discuss the question of which residues are sufficiently important for protein
      protein interaction to be under notable evolutionary pressure. Its interest stems
      from the applicability of this knowledge in the reverse direction, to detect a
      protein-protein interface on a single protomer, starting from the rate of
      mutation of participating residues. Using the analysis of trajectories produced
      by the molecular dynamics simulations, we suggest that, in the case of water
      soluble proteins, a large fraction of evolutionarily privileged residues can be
      found by considering the dynamic behavior of the protein interface and by looking
      for residues which exchange water molecules with the bulk of the solvent
      outstandingly slowly (tentatively termed "dry residues"). We show that the dry
      interface residues are better conserved across homologues than the generic
      "geometric footprint" and can be quite reliably detected through comparative
      analysis of protein homologues, without strong dependence on the choice of
      method. Furthermore, we show that dry residues distinguish themselves through a
      set of biophysical properties consistent with the known mechanisms of protein
      oligomerization: their compositional shift toward nonpolar, overlap, and co
      location with residues exhibiting low mobility, their two- to threefold increased
      propensity over the rest of the geometric footprint to form hydrogen bonds, and
      four- to almost tenfold increased likelihood to participate in formation of salt
      bridges. These properties, consistently, help understand the observed increase in
      the evolutionary pressure that dry residues experience.

PMID- 17434531
TI  - Crystal structure of the archaeal heat shock regulator from Pyrococcus furiosus:
      a molecular chimera representing eukaryal and bacterial features.
AB  - We report here the crystal structure of a protein from Pyrococcus furiosus (Phr)
      that represents the first characterized heat shock transcription factor in
      archaea. Phr specifically represses the expression of heat shock genes at
      physiological temperature in vitro and in vivo but is released from the promoters
      upon heat shock response. Structure analysis revealed a stable homodimer, each
      subunit consisting of an N-terminal winged helix DNA-binding domain (wH-DBD) and
      a C-terminal antiparallel coiled coil helical domain. The overall structure shows
      as a molecular chimera with significant folding similarity of its DBD to the
      bacterial SmtB/ArsR family, while its C-terminal part was found to be a remote
      homologue of the eukaryotic BAG domain. The dimeric protein recognizes a
      palindromic DNA sequence. Molecular docking and mutational analyses suggested a
      novel binding mode in which the major specific contacts occur at the minor groove
      interacting with the strongly basic wing containing a cluster of three arginine
      residues.

PMID- 17434532
TI  - Structural basis for bile salt inhibition of pancreatic phospholipase A2.
AB  - Bile salt interactions with phospholipid monolayers of fat emulsions are known to
      regulate the actions of gastrointestinal lipolytic enzymes in order to control
      the uptake of dietary fat. Specifically, on the lipid/aqueous interface of fat
      emulsions, the anionic portions of amphipathic bile salts have been thought to
      interact with and activate the enzyme group-IB phospholipase A2 (PLA2) derived
      from the pancreas. To explore this regulatory process, we have determined the
      crystal structures of the complexes of pancreatic PLA2 with the naturally
      occurring bile salts: cholate, glycocholate, taurocholate,
      glycochenodeoxycholate, and taurochenodeoxycholate. The five PLA2-bile salt
      complexes each result in a partly occluded active site, and the resulting ligand
      binding displays specific hydrogen bonding interactions and extensive hydrophobic
      packing. The amphipathic bile salts are bound to PLA2 with their polar hydroxyl
      and sulfate/carboxy groups oriented away from the enzyme's hydrophobic core. The
      impaired catalytic and interface binding functions implied by these structures
      provide a basis for the previous numerous observations of a biphasic dependence
      of the rate of PLA2 catalyzed hydrolysis of zwitterionic glycerophospholipids in
      the presence of bile salts. The rising or activation phase is consistent with
      enhanced binding and activation of the bound PLA2 by the bile salt induced
      anionic charge in a zwitterionic interface. The falling or inhibitory phase can
      be explained by the formation of a catalytically inert stoichiometric complex
      between PLA2 and any bile salts in which it forms a stable complex. The model
      provides new insight into the regulatory role that specific PLA2-bile salt
      interactions are likely to play in fat metabolism.

PMID- 17434533
TI  - AfsR recruits RNA polymerase to the afsS promoter: a model for transcriptional
      activation by SARPs.
AB  - AfsR, a protein belonging to the Streptomyces antibiotic regulatory protein
      (SARP) family, is a global regulator of secondary metabolism in Streptomyces
      coelicolor A3(2). AfsR consists of three major functional domains: an N-terminal
      SARP domain, a central ATPase domain, and a C-terminal tetratrico peptide repeat
      (TPR) domain. Two truncated AfsR proteins, AfsRDeltaTPR containing the SARP and
      ATPase domains and AfsRDeltaC containing only the SARP domain, exhibited the same
      DNA-binding specificity as that of full-length AfsR. Two monomers bound
      cooperatively to a direct repeat located eight nucleotides 5' to the -10 element
      of the afsS promoter. Both truncated AfsR proteins, as well as full-length AfsR,
      were able to form ternary complexes with the afsS promoter and RNA polymerase
      (RNAP), although RNAP alone could not bind to the DNA. The DNA-(AfsRDeltaC)(2)
      RNAP complex was capable of initiating afsS transcription in vitro, indicating
      that the ATPase and TPR domains are dispensable for the basic function of AfsR as
      a transcriptional activator. However, the ATPase domain was required to fully
      compensate for the defect in actinorhodin production in an afsR-disrupted mutant,
      suggesting that the ATPase domain exerts a regulatory function on the basic SARP
      domain. Deletion or addition of even a single nucleotide between the AfsR-binding
      site and the -10 element of the afsS promoter abolished afsS transcription both
      in vitro and in vivo, indicating that the recruitment of RNAP by AfsR to the
      correct location relative to the -10 element is critical for transcriptional
      activation. Since SARP-binding sites with similar direct repeats are located at
      the same position relative to the -10 element of their target promoters as is the
      afsS binding site, the SARP family members presumably activate transcription of
      their targets by recruiting RNAP to the promoter, where a ternary DNA-SARP-RNAP
      complex competent for transcriptional initiation is formed.

PMID- 17434534
TI  - Mapping putative contact sites between subunits in a bacterial ATP-binding
      cassette (ABC) transporter by synthetic peptide libraries.
AB  - The maltose ATP-binding cassette transporter of Salmonella typhimurium is
      composed of the soluble periplasmic receptor, MalE, and a membrane-associated
      complex comprising one copy each of the pore-forming hydrophobic subunits, MalF
      and MalG, and of a homodimer of the ATP-hydrolyzing subunit, MalK. During the
      transport process the subunits are thought to undergo conformational changes that
      might transiently alter molecular contacts between MalFG and MalK(2). In order to
      map sites of subunit-subunit interactions we have used a comprehensive peptide
      mapping approach comprising large-scale microsynthesis of labelled probes and
      array techniques. In particular, we screened the binding of (i) MalFG-derived
      soluble biotinylated peptides to immobilized MalK, and (ii) radiolabelled MalK to
      MalFG-derived cellulose membrane-bound peptides. The first approach identified
      seven peptides (10mers) each of MalF and MalG that specifically bound to MalK.
      The peptides were localized to TMDs 3 and 6, periplasmic loop P4 and cytoplasmic
      loops C2 and C3 of MalF, while MalG-derived peptides localized to the N terminus,
      TMDs 4-6, periplasmic loop P1 and cytoplasmic loop C2. Peptides from C3 and C2,
      respectively, of MalF and MalG partially encompass the conserved EAA-motif, known
      to be crucial for interaction with MalK. These results were basically confirmed
      by screening MalFG-derived peptide arrays consisting of 16mers or 31mers with
      radiolabelled MalK. This approach also allowed us to perform complete
      substitutional analyses of peptides in question. The results led to the
      construction of MalFG variants that were subsequently analyzed for functional
      consequences in vivo. Growth experiments revealed that most of the mutations had
      no phenotype, suggesting that the mutated residues themselves are not critical
      but part of a discontinuous binding site. However, two novel mutations affecting
      residues from the EAA motifs of MalF (Ile417Glu) and MalG (Phe203Gln/Asn),
      respectively, displayed severe growth defects, indicating their functional
      importance. Together, these experimental outcomes identify specific molecular
      contacts made between MalK and MalFG that extend beyond the well-characterized
      EAA motif.

PMID- 17434536
TI  - Weak trophic interactions and the balance of enriched metacommunities.
AB  - Weak trophic interactions have been shown to promote the stability of ecological
      food webs characterized by perfect mixing. However, their importance at the
      landscape level and response to enrichment has not been extensively examined. In
      this paper we examine the food-web model explored by McCann et al. [1998. Weak
      trophic interactions and the balance of nature. Nature 395, 794-798]. The model
      is expanded into a metacommunity construct where local communities are coupled
      through global or local dispersal. We analyze global and local stability, as well
      as spatial synchrony in relation to trophic interaction strength and dispersal
      regimes. Results reveal that weak interactions can operate through two scale
      dependent mechanisms: (i) under low local dispersal regimes, local stabilization
      of each community under weak interactions directly scales-up to global stability.
      (ii) Under high local dispersal, asynchronous local destabilization associated
      with weak interactions proves the driver behind global stability. In the face of
      enrichment, weak trophic interactions are shown to be instrumental in promoting
      global stability when dispersal is local. These results demonstrate how the
      importance of weak trophic interactions can be generalized at the landscape level
      despite contrary local predictions.

PMID- 17434535
TI  - A threefold RNA-protein interface in the signal recognition particle gates native
      complex assembly.
AB  - Intermediate states play well-established roles in the folding and misfolding
      reactions of individual RNA and protein molecules. In contrast, the roles of
      transient structural intermediates in multi-component ribonucleoprotein (RNP)
      assembly processes and their potential for misassembly are largely unexplored.
      The SRP19 protein is unstructured but forms a compact core domain and two
      extended RNA-binding loops upon binding the signal recognition particle (SRP)
      RNA. The SRP54 protein subsequently binds to the fully assembled SRP19-RNA
      complex to form an intimate threefold interface with both SRP19 and the RNA and
      without significantly altering the structure of SRP19. We show, however, that the
      presence of SRP54 during SRP19-RNA assembly dramatically alters the folding
      energy landscape to create a non-native folding pathway that leads to an aberrant
      SRP19-RNA conformation. The misassembled complex arises from the surprising
      ability of SRP54 to bind rapidly to an SRP19-RNA assembly intermediate and to
      interfere with subsequent folding of one of the RNA binding loops at the three
      way protein-RNA interface. An incorrect temporal order of assembly thus readily
      yields a non-native three-component ribonucleoprotein particle. We propose there
      may exist a general requirement to regulate the order of interaction in multi
      component RNP assembly reactions by spatial or temporal compartmentalization of
      individual constituents in the cell.

PMID- 17434537
TI  - Support for a hypothesis on the offspring sex ratios of hepatitis B carriers.

PMID- 17434538
TI  - Large-conductance Ca2+-activated K+ currents blocked and impaired by homocysteine
      in human and rat mesenteric artery smooth muscle cells.
AB  - Plenty of evidence suggests that increased blood levels of homocysteine (Hcy) are
      an independent risk factor for the development of vascular diseases, but the
      underlying mechanisms are not well understood. It is well known that the larger
      conductance Ca(2+)-activated K(+) channels (BK(Ca)) play an essential role in
      vascular function, so the present study was conducted to determine direct effects
      of Hcy on BK(Ca) channel properties of smooth muscle cells. Whole-cell patch
      clamp recordings were made in mesenteric artery smooth muscle cells isolated from
      normal rat and patients to investigate effects of 5, 50 and 500 microM Hcy on
      BK(Ca), the main current mediating vascular responses in these cells. In human
      artery smooth muscle cells, maximum BK(Ca) density (measured at +60 mV) was
      inhibited by about 24% (n=6, P<0.05). In rat artery smooth muscle cells, maximum
      BK(Ca) density was decreased by approximately 27% in the presence of 50 microM
      Hcy (n=8, P<0.05). In addition, when rat artery smooth muscle cells was treated
      with 50 microM Hcy for 24 h, maximum BK(Ca) density decreased by 58% (n=5,
      P<0.05). These data suggest that Hcy significantly inhibited BK(Ca) currents in
      isolated human and rat artery smooth muscle cells. BK(Ca) reduced and impaired by
      elevated Hcy levels might contribute to abnormal vascular diseases.

PMID- 17434539
TI  - PCB, PCDD/F and PBDE levels and profiles in crustaceans from the coastal waters
      of Brittany and Normandy (France).
AB  - Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were analysed in
      the muscle of various edible marine crustaceans (spider crab, edible crab, velvet
      swimming crab and Norway lobster) from the Brittany and Normandy coasts (France).
      The highest concentrations were measured in species collected from Antifer (Seine
      Bay). PCB and PBDE patterns in crustacean muscles were similar and independent of
      the geographical area with the predominance of the high chlorinated PCBs (CB153,
      138, 118 and 180), and of a few PBDE congeners (BDE47, BDE99, BDE100 and BDE28).
      Oppositely, dioxin contamination differed with site. The major component in
      crustaceans from the Seine Bay was 2378-TCDF, whereas specimens from cleaner
      areas had higher relative concentrations of OCDD. Finally, the comparison of the
      spider crab contaminant profiles to those measured in mussel and sea bass
      highlighted two different trends: decapod crustaceans possess relatively strong
      capacity to metabolise PCBs and PBDEs; however these species might be used as
      bioindicators for dioxin pollution monitoring in the marine coastal environment.

PMID- 17434540
TI  - Dehydroevodiamine attenuates tau hyperphosphorylation and spatial memory deficit
      induced by activation of glycogen synthase kinase-3 in rats.
AB  - Tau hyperphosphorylation and memory deficit are characteristic alterations of
      Alzheimer's disease (AD), and glycogen synthase kinase-3 (GSK-3) plays a crucial
      role in these AD-like changes. We have reported that activation of GSK-3 through
      ventricular injection of wortmannin and GF-109203X (WT/GFX, 100 microM each)
      induces tau hyperphosphorylation and memory impairment of rats [Liu, S.J. et al.,
      2003. Overactivation of glycogen synthase kinase-3 by inhibition of
      phosphoinositol-3 kinase and protein kinase C leads to hyperphosphorylation of
      tau and impairment of spatial memory. J. Neurochem. 87, 1333-1344]. By using this
      model, we explored in the present study the effects of dehydroevodiamine (DHED),
      a quinazoline alkaloid isolated from Evodia rutaecarpa Bentham, on the memory
      retention, tau phosphorylation and the activity of GSK-3. We found that pre
      administration of DHED through vena caudalis for 1 week efficiently improved the
      WT/GFX-induced spatial memory retention impairment of the rats; it also
      antagonized tau hyperphosphorylation at multiple AD sites and arrested the
      overactivation of GSK-3 induced by WT/GFX. Our study gave the first in vivo
      evidence that DHED could suppress the overactivation of GSK-3 and improve tau
      hyperphosphorylation and spatial memory deficit of the rats, suggesting that this
      chemical may be served as a candidate for arresting AD-like pathological and
      behavioral alterations.

PMID- 17434541
TI  - The effect of cinnarizine and cocculus indicus on simulator sickness.
AB  - Pensacola Simulator Sickness Questionnaire (SSQ) is a valuable method to analyse
      symptoms evoked by exposure to a flight simulator environment that can also be
      adopted to evaluate the effectiveness of preventive tools, aiming at reducing
      simulator sickness (SS). In this study we analysed SSQ data in subjects
      undergoing a standard ground based spatial disorientation training inside a
      flight simulator, in order to evaluate the SS prevention obtained with two
      different pharmacological tools. Twelve males volunteers participated to an
      experimental design based on a double-blind, balanced administration of either 30
      mg cinnarizine (CIN), or Cocculus Indicus 6CH (COC), or placebo (PLC) before one
      trial of about one hour spent inside a spatial disorientation trainer. All
      subjects underwent the three different conditions (CIN, COC, PLC) during 3 non
      consecutive days separated by at least 2 weeks. During each experimental day, all
      subjects filled in SSQ. In addition, both postural instability (with the use of a
      static stabilometric platform), and sleepiness symptoms were evaluated. All the
      tests were performed before and after the simulated flight, at different times,
      in one-and-half-hour intervals. Results indicated a strong increase of sickness
      after flight simulation that linearly decreased, showing pre-simulator scores
      after 1.30 hours. In contrast to both PLC and COC, CIN showed significant side
      effects immediately following flight simulation, with no benefit at the
      simultaneous SSQ scores. Globally, no highly significant differences between COC
      and PLC were observed, although a minor degree of postural instability could be
      detected after COC administration. As far as the present exposure to a simulator
      environment is concerned, none of the pharmacological tools administered in this
      study resulted effective in reducing SS symptoms as detected by the SSQ.
      Moreover, CIN significantly increased sleepiness and postural instability in most
      subjects.

PMID- 17434542
TI  - Duodenal pain and spinal morphine induce conditioned taste aversion in rats.
AB  - Conditioned taste aversion (CTA) is a behavioural response essential to the
      survival of an individual. The combination of taste and odour of most foods
      provides a strong conditioned stimulus (CS) for an animal to respond in an
      appropriate way to any harmful unconditioned stimuli (US) that follow. The most
      widely used conditioned stimuli are drinkable sweet solutions, such as saccharin
      and sucrose. CTA-like responses are also found for environmental unconditioned
      stimuli, but these usually take longer training. In the present study, the
      aversive nature of a duodenal distention with an implanted balloon catheter was
      studied in freely moving rats using either CTA against a sucrose solution, or a
      light-dark passive avoidance (PA) paradigm. In addition, the effect of spinal
      morphine on CTA and the cardiovascular response to duodenal distention were
      studied. CTA could be induced by a single, but long-lasting 20-minute duodenal
      distention, which did not induce PA behaviour in a light-dark box. Spinal
      infusion of morphine alone induced CTA, suggesting that the model is unsuitable
      to investigate spinal pharmacological modulation of visceral pain. Spinal
      morphine did reduce the cardiovascular response to duodenal distention,
      strengthening its validity as a visceral pain model. Since CTA is a complicating
      factor in the field of chemotherapy in cancer patients and spinal morphine causes
      nausea and vomiting in humans, CTA may also complicate spinal drug treatment or
      anaesthesia.

PMID- 17434543
TI  - Hypoglycemia activates arousal-related neurons and increases wake time in adult
      rats.
AB  - Hypoglycemia resulting from excess of exogenous or endogenous insulin elicits
      central nervous system activation that contributes to counterregulatory hormone
      secretion. In adult humans without diabetes, hypoglycemia occurring during sleep
      usually produces cortical activation with awakening. However, in adult humans
      with type 1 diabetes, hypoglycemic arousal appears blunted or absent. We
      hypothesized that insulin injection sufficient to produce hypoglycemia would
      induce awakening in adult male rats. Polysomnographic studies were carried out to
      characterize the effect of insulin injection on measures of sleep and waking
      during a circadian time of increased sleep. Compared to a baseline day, insulin
      treatment more than doubled the time spent awake, from 18.4+/-2.6% after saline
      injection to 48.0+/-5.5% after insulin. Insulin injection also reduced rapid eye
      movement sleep (REMS) from 27.3+/-1.8% to 5.6+/-1.3%. The percent of time in non
      REM sleep (NREMS) sleep was not different between saline and insulin days,
      however, NREMS after insulin was fragmented, with increased number and decreased
      duration of episodes. These electrophysiological data indicate that insulin
      induced hypoglycemia is an arousing stimulus in rats, as in nondiabetic adult
      humans. We also studied the effect of insulin on activation of selected arousal
      related neurons using immunohistochemical detection of Fos. Fos-immunoreactivity
      increased in orexin (OX) neurons after insulin, from 8.7+/-4.9% after saline
      injection to 37+/-9% after insulin. Basal forebrain cholinergic nuclei also
      showed increased Fos-immunoreactivity after insulin. These correlated behavioral
      and histological data provide targets for future studies of the neural pathways
      underlying hypoglycemic arousal.

PMID- 17434544
TI  - Sugar-sweetened and artificially sweetened soft drinks in association to
      restrained, external and emotional eating.
AB  - We studied sugar-sweetened soft drinks and light soft drinks in their
      associations to psychological constructs of eating behavior and demographic data
      for adults and children. Soft drink intakes were assessed by consumption of soft
      drinks in number of days the last week, and eating behavior was measured by the
      Dutch Eating Behaviour Questionnaire (DEBQ). The sample included 3265 men and
      women, and their 12-year old children, originating from Swedish national
      databases. Associations to younger age and lower education in adults were in
      particular apparent for sugar-sweetened soft drinks. Consumption of sugar
      sweetened soft drinks was further associated to less restrained and more external
      eating in adults. In contrast, light soft drinks were associated with higher BMI,
      more restrained eating and also more emotional eating in adults. For the children
      these associations were generally weaker. Sugar-sweetened soft drinks are
      consumed by persons with a lower education, who furthermore are less prone to
      attempt to restrict their calorie intake, and by some of those who are sensitive
      to external stimuli of foods. Light soft drinks are rather chosen by the more
      heavy persons who try to restrict their energy intake perhaps in order to control
      the body weight, and more unexpectedly, by adults who eat for comfort. Being more
      sensitive to an external stimulus of food such as taste seems to imply proneness
      to consume sugar-sweetened soft drinks instead of the light versions. Light soft
      drinks may be perceived as an adequate substitute in the use of foods for
      comfort, meaning the sweet taste may be sufficient for this purpose.

PMID- 17434545
TI  - An angiotensin II receptor blocker increases sexual behavior in type 2 diabetic
      mice.
AB  - The present study was conducted to examine the effects of olmersartan,
      angiotensin (ANG) II type 1 (AT(1)) receptor antagonist, on the sexual function
      in type 2 diabetes model mice. Twenty-week-old KK/Ta mice were used as a model of
      type 2 diabetes. Age-matched ICR and BALB/C mice were used as non-diabetic
      controls. The animals were fed powder chow either with or without olmesartan (7.5
      microg/g in chow) for 4 weeks. The levels of sexual behavior, activity, and
      anxiety were then examined between the groups treated with and without
      olmesartan. The KK/Ta mice treated with olmesartan exhibited a significant
      increase in the number of mounts and intromission and a decrease in the latency
      to the first mount in comparison to the KK/Ta mice treated without olmesartan.
      These effects of olmesartan were not observed in the non-diabetic BALB/C and ICR
      mice. In addition, the olmesartan treatment did not affect the activity and
      anxiety regardless of the mouse strain. These findings suggest that the
      interaction between ANG II and AT(1) receptor may be involved in the pathogenesis
      of the sexual dysfunction associated with type 2 diabetes and a blockade of ANG
      II may therefore be a potentially useful treatment for male sexual dysfunction in
      type 2 diabetes.

PMID- 17434546
TI  - Fostering and environmental enrichment ameliorate anxious behavior induced by
      early weaning in Balb/c mice.
AB  - Postnatal stimuli affect many aspects of physiological and behavioral
      development. In mice, earlier weaning augments anxiety, putatively as a result of
      removing mother-pup interactions during the weaning period. Here, we examined the
      ameliorating effects of social and environmental enrichment on anxiety related to
      early weaning. Mice weaned at postpartum day 14 were fostered by virgin females,
      who displayed some nursing behavior during the 1-week fostering period. In
      elevated plus-maze tests, 10-week-old pups reared with a foster mother spent more
      time in the open arms than early-weaned mice, and entered into the open arms at a
      rate between that of normally- and early-weaned mice. Subsequently, the mice from
      each rearing group were transferred into either standard housing or housing
      enriched with toys that were changed periodically. Elevated plus-maze tests were
      conducted again when the mice were 18 and 26 weeks old. The enriched environment
      increased the duration of time spent in the open arms, but the magnitude of the
      effect varied with the rearing condition. Furthermore, mice that lived in the
      enriched environment showed lower activity than those kept in standard housing.
      These results suggest that fostering after early weaning attenuates increases in
      anxiety levels, and maternal care during this period may be important in the
      development of an offspring's emotionality. Environmental stimuli in adulthood
      may act to blunt the effects deprivation in early life.

PMID- 17434547
TI  - Effects of very low calorie diet induced body weight loss with or without human
      pegylated recombinant leptin treatment on changes in ghrelin and adiponectin
      concentrations.
AB  - The aim of the study was to investigate the effects of energy restriction with or
      without pegylated recombinant leptin (PEG-leptin) treatment on ghrelin,
      adiponectin, insulin and glucose concentrations. A randomized double-blind
      placebo-controlled trial was performed in 24 moderately overweight/obese men. PEG
      leptin or placebo was administered weekly for 6 weeks, combined with a restricted
      energy intake of 2.1 MJ/d. At days 1, 25, and 46 a blood sample was taken and
      body-weight (BW) was measured. Days 1-25 was named phase 1, and days 25-46 phase
      2. During phase 1 the rate of BW loss was significantly higher in the PEG-leptin
      compared to the placebo group (0.38+/-0.07 vs 0.32+/-0.06 kg/d, p<0.05). The rate
      of BW loss during phase 2 was 0.24+/-0.08 and 0.18+/-0.09 kg/d, respectively
      (p=0.07). In both groups the rate of BW loss during phase 1 was significantly
      higher than during phase 2 (p<0.001). Energy balance (EB) was significantly more
      negative during phase 1 than during phase 2 in both groups (p<0.0005). During
      phase 1 insulin, glucose and adiponectin decreased significantly in both groups.
      Adiponectin and ghrelin concentrations changed in the opposite direction between
      phase 1 and phase 2 (p<0.05). Initial BW loss due to a considerable negative EB
      induced decreased ghrelin, adiponectin, insulin and glucose levels. However, when
      EB became less negative and the rate of BW loss decreased, these changes were
      reversed for adiponectin and ghrelin. The PEG-leptin injections did not have an
      effect on the changes in insulin, glucose and adiponectin, but had an effect on
      the changes in ghrelin concentrations.

PMID- 17434548
TI  - A vanadium-dependent bromoperoxidase in the marine red alga Kappaphycus alvarezii
      (Doty) Doty displays clear substrate specificity.
AB  - Bromoperoxidase activity was initially detected in marine macroalgae belonging to
      the Solieriaceae family (Gigartinales, Rhodophyta), including Solieria robusta
      (Greville) Kylin, Eucheuma serra J. Agardh and Kappaphycus alvarezii (Doty) Doty,
      which are important industrial sources of the polysaccharide carrageenan.
      Notably, the purification of bromoperoxidase was difficult because due to the
      coexistence of viscoid polysaccharides. The activity of the partially purified
      enzyme was dependent on the vanadate ion, and displayed a distinct substrate
      spectrum from that of previously reported vanadium-dependent bromoperoxidases of
      marine macroalgae. The enzyme was specific for Br- and I- ions and inactive
      toward F- and Cl-. The K(m) values for Br- and H2O2 were 2.5x10(-3) M and 8.5x10(
      5) M, respectively. The halogenated product, dibromoacetaldehyde, that
      accumulated in K. alvarezii was additionally determined.

PMID- 17434549
TI  - On an extension of R.A. Fisher's result on the dynamics of the reproductive
      value.
AB  - A classical result by Fisher concerning reproductive value dynamics is extended
      to the case of varying vital rates with a constant cohort Lotka's r. Based on the
      demographic potential approach, a generalization of the concept of reproductive
      value is introduced, which exhibits exponential dynamics both in the classical
      case of constant vital rates and in a wider class of populations. The generalized
      reproductive value introduced in this paper fits the classical interpretation by
      Fisher as a discounted sum of future births in the general class of models
      addressed here. Our results show when Fisher's classical results may be used as
      good approximations. They could also be of importance for estimating the fitness
      of biological populations, aggregate population modeling, and studying the long
      term consequences of varying vital rates.

PMID- 17434550
TI  - Improving the scientific foundation for mixtures joint toxicity and risk
      assessment: contributions from the SOT mixtures project--introduction.
AB  - Risk assessments are enhanced when policy and other decision-makers have access
      to experimental science designed to specifically inform key policy questions.
      Currently, our scientific understanding and science policy for environmental
      mixtures are based largely on extrapolating from and combining data in the
      observable range of single chemical toxicity to lower environmental
      concentrations and composition, i.e., using higher dose data to extrapolate and
      predict lower dose toxicity. There is a growing consensus that the default
      assumptions underlying those mixtures risk assessments that are conducted in the
      absence of actual mixtures data rest on an inadequate scientific database. Future
      scientific research should both build upon the current science and advance
      toxicology into largely uncharted territory. More precise approaches to better
      characterize toxicity of mixtures are needed. The Society of Toxicology (SOT)
      sponsored a series of panels, seminars, and workshops to help catalyze and
      improve the design and conduct of experimental toxicological research to better
      inform risk assessors and decision makers. This paper summarizes the activities
      of the SOT Mixtures Program and serves as the introductory paper to a series of
      articles in this issue, which hope to inspire innovative research and challenge
      the status quo.

PMID- 17434551
TI  - Characterization of highly toxic type 2 ribosome-inactivating proteins from
      Adenia lanceolata and Adenia stenodactyla (Passifloraceae).
AB  - From the caudices of the Passifloraceae Adenia lanceolata and A. stenodactyla,
      two lectins called lanceolin and stenodactylin, respectively, were purified by
      affinity chromatography on CL Sepharose 6B. The lectins are glycoproteins with
      M(r) 61,243 (lanceolin) and 63,131 (stenodactylin), consisting of an enzymatic A
      chain linked to a larger B chain with lectin properties, with N-terminal amino
      acid sequences similar to that of volkensin, the toxic lectin from A. volkensii.
      The lectins agglutinate red blood cells, inhibit protein synthesis both by a cell
      free system and by whole cells, and depurinate ribosomes and DNA, but not tRNA or
      poly(A). They are highly toxic to cells, in which they induce apoptosis, and to
      mice, with LD(50)s 8.16 microg/kg (lanceolin) and 2.76 microg/kg (stenodactylin)
      at 48 h. Thus, lanceolin and stenodactylin have all the properties of the toxic
      type 2 ribosome-inactivating proteins and are amongst the most potent toxins of
      plant origin.

PMID- 17434552
TI  - Recombinant simian varicella viruses induce immune responses to simian
      immunodeficiency virus (SIV) antigens in immunized vervet monkeys.
AB  - The varicella-zoster virus (VZV) Oka vaccine offers potential as a recombinant
      vaccine against other pathogens. In this study, recombinant simian varicella
      viruses (rSVV) expressing simian immunodeficiency virus (SIV) envelope (env,
      gp130) and gag antigens were constructed. Expression of the SIV env and gag
      transcripts and antigens in rSVV-infected Vero cells was confirmed. The rSVV
      SIVenv and rSVV-SIVgag viruses replicated as efficiently as wild-type SVV in cell
      culture. The immunogenicity of rSVV-SIVenv and rSVV-SIVgag was investigated in
      immunized vervet monkeys. Humoral immune responses to the SIV gp130 and gag
      antigens were detected as early as 4 weeks after the initial immunization with
      higher antibody titers following a booster immunization. Cellular immune
      responses against the SIV gp130 antigen were detected by ELISPOT assay. The rSVV
      established latent infection in neural ganglia. A subsequent study will evaluate
      the ability of rSVV vaccines expressing SIV antigens to protect nonhuman primates
      against simian AIDS.

PMID- 17434553
TI  - ICAM-3 influences human immunodeficiency virus type 1 replication in CD4(+) T
      cells independent of DC-SIGN-mediated transmission.
AB  - We investigated the role of ICAM-3 in DC-SIGN-mediated human immunodeficiency
      virus (HIV) infection of CD4(+) T cells. Our results demonstrate that ICAM-3 does
      not appear to play a role in DC-SIGN-mediated infection of CD4(+) T cells as
      virus is transmitted equally to ICAM-3(+) or ICAM-3(-) Jurkat T cells. However,
      HIV-1 replication is enhanced in ICAM-3(-) cells, suggesting that ICAM-3 may
      limit HIV-1 replication. Similar results were obtained when SIV replication was
      examined in ICAM-3(+) and ICAM-3(-) CEMx174 cells. Furthermore, while ICAM-3 has
      been proposed to play a co-stimulatory role in T cell activation, DC-SIGN
      expression on antigen presenting cells did not enhance antigen-dependent
      activation of T cells. Together, these data indicate that while ICAM-3 may
      influence HIV-1 replication, it does so independent of DC-SIGN-mediated virus
      transmission or activation of CD4(+) T cells.

PMID- 17434554
TI  - Development of a low-cost, insect larvae-derived recombinant subunit vaccine
      against RHDV.
AB  - Vaccine antigens against rabbit hemorrhagic disease virus (RHDV) are currently
      derived from inactivated RHDV obtained from livers of experimentally infected
      rabbits. Several RHDV-derived recombinant immunogens have been reported. However,
      their application in vaccines has been restricted due to their high production
      costs. In this paper, we describe the development of an inexpensive, safe, stable
      vaccine antigen for RHDV. A baculovirus expressing a recombinant RHDV capsid
      protein (VP60r) was used to infect Trichoplusia ni insect larvae. It reached an
      expression efficiency of 12.5% of total soluble protein, i.e. approximately 2 mg
      of VP60r per larva. Preservation of the antigenicity and immunogenicity of the
      VP60r was confirmed by immunological and immunization experiments. Lyophilized
      crude larvae extracts, containing VP60r, were stable, at room temperature, for at
      least 800 days. In all cases, rabbits immunized with a single dose of VP60r by
      the intramuscular route were protected against RHDV challenge. Doses used were as
      low as 2 microg of VP60r in the presence of adjuvant or 100 microg without one.
      Orally administered VP60r in the absence of an adjuvant gave no protection. The
      potential costs of an RHDV vaccine made using this technology would be reduced
      considerably compared with producing the same protein in insect cells maintained
      by fermentation. In conclusion, the larva expression system may provide a broad
      based strategy for production of recombinant subunit antigens (insectigens) for
      human or animal medicines, especially when production costs restrain their use.

PMID- 17434555
TI  - The intrinsic antiretroviral factor APOBEC3B contains two enzymatically active
      cytidine deaminase domains.
AB  - The mammalian APOBEC3 proteins are cytidine deaminases that function as
      inhibitors of retrovirus replication and retrotransposon mobility. An issue that
      has remained controversial is whether the editing of deoxycytidine residues to
      deoxyuridine is necessary and sufficient for this inhibition or whether APOBEC3
      proteins also exert a second, distinct inhibitory mechanism. Here, we present an
      analysis of the ability of mutants of APOBEC3G and APOBEC3B, both of which
      contain two consensus cytidine deaminase active sites, to inhibit the replication
      of human immunodeficiency virus. Our data confirm that APOBEC3G only contains a
      single, carboxy-terminal active site but, surprisingly, reveal that both cytidine
      deaminase consensus sequences in APOBEC3B are enzymatically active. Enzymatically
      inactive mutant forms of APOBEC3G and APOBEC3B were found to retain the ability
      to inhibit the infectivity of HIV-1 virions produced in their presence by
      approximately 4-fold and approximately 8-fold, respectively. While this
      inhibition was significantly less than the level seen with wild-type forms of A3G
      or A3B, these data, nevertheless argue that the inhibition of HIV-1 by APOBEC3
      proteins is at least partly independent of DNA editing.

PMID- 17434556
TI  - Characterisation of a novel recombination event in the norovirus polymerase gene.
AB  - This communication describes a novel recombination event in the norovirus genome.
      Similarity plot analysis of a nucleotide fragment (1003 bp) amplified from a
      norovirus positive clinical specimen (IrlN05771) identified a previously
      undescribed recombination point in the 3' region of the polymerase gene
      (nucleotide position 4889 bp). Nucleotide multiple alignments demonstrated that
      Irl05N771 shared 78.6% and 94% identity with all other Irish norovirus sequences
      before and after the recombination point, respectively and confirmed the sequence
      as a genogroup II/type 4 recombinant. Irl05N771 shared more identity with Asian
      norovirus sequences. This is the first description of recombination within the
      norovirus polymerase and highlights the continuous genetic evolution of
      noroviruses.

PMID- 17434557
TI  - Ebola virus-like particle-induced activation of NF-kappaB and Erk signaling in
      human dendritic cells requires the glycoprotein mucin domain.
AB  - Dendritic cells (DCs), important early targets of Ebola virus (EBOV) infection in
      vivo, are activated by Ebola virus-like particles (VLPs). To better understand
      this phenomenon, we have systematically assessed the response of DCs to VLPs of
      different compositions. VLPs containing the viral matrix protein (VP40) and the
      viral glycoprotein (GP), were found to induce a proinflammatory response highly
      similar to a prototypical DC activator, LPS. This response included the
      production of several proinflammatory cytokines, activation of numerous
      transcription factors including NF-kappaB, the functional importance of which was
      demonstrated by employing inhibitors of NF-kappaB activation, and activation of
      ERK1/2 MAP kinase. In contrast, VLPs constituted with a mutant GP lacking the
      heavily glycosylated mucin domain showed impaired NF-kappaB and Erk activation
      and induced less DC cytokine production. We conclude that the GP mucin domain is
      required for VLPs to stimulate human dendritic cells through NF-kappaB and MAPK
      signaling pathways.

PMID- 17434558
TI  - Quasispecies of bovine enteric and respiratory coronaviruses based on complete
      genome sequences and genetic changes after tissue culture adaptation.
AB  - The genetic diversity of 2 pairs (AH65 and AH187) of wild type bovine
      coronaviruses (BCoV) sequenced directly from nasal (respiratory) and rectal
      (enteric) swabs of two feedlot calves with respiratory and enteric symptoms
      [Hasoksuz, M., Sreevatsan, S., Cho, K.O., Hoet, A.E., Saif, L.J., 2002b.
      Molecular analysis of the S1 subunit of the spike glycoprotein of respiratory and
      enteric bovine coronavirus isolates. Virus Res. 84 (1-2), 101-109.]. was
      analyzed. Sequence analysis of the complete genomes revealed differences at 123
      and 149 nucleotides (nt) throughout the entire genome between the respiratory and
      enteric strains for samples AH65 and AH187, respectively, indicating the presence
      of intra-host BCoV quasispecies. In addition, significant numbers of sequence
      ambiguities were found in the genomes of some BCoV-R and BCoV-E strains,
      suggesting intra-isolate quasispecies. The tissue culture (TC) passaged
      counterparts of AH65 respiratory BCoV (AH65-R-TC) and enteric BCoV (AH65-E-TC)
      were also sequenced after 14 and 15 passages and 1 plaque purification in human
      rectal tumor cells (HRT-18), respectively. Compared to the parental wild type
      strains, tissue culture passage generated 104 nt changes in the AH65-E-TC isolate
      but only 8 nt changes in the AH65-R-TC isolate. Particularly noteworthy, the
      majority of nucleotide changes in the AH65-E-TC isolate occurred at the identical
      positions as the mutations occurring in the AH65-R strain from the same animal.
      These data suggest that BCoV evolves through quasispecies development, and that
      enteric BCoV isolates are more prone to genetic changes and may mutate to
      resemble respiratory BCoV strains after tissue culture passage.

PMID- 17434560
TI  - Ultrasonically induced degradation of 2-methylisoborneol and geosmin.
AB  - 2-Methylisoborneol (MIB) and geosmin (GSM) are taste and odor compounds produced
      by cyanobacteria in surface waters. While the strong odors and musty flavors of
      MIB and GSM are generally associated with poor water quality, the removal of
      these semi-volatile compounds presents a significant challenge to drinking water
      providers. Likewise in aquaculture, accumulation of these compounds in fish meat
      leads to quality problems and reduces marketability. Conventional water
      treatments are ineffective at removing low concentration of odor compounds. We
      report herein ultrasonic irradiation at 640 kHz leads to rapid degradation of MIB
      and GSM. While radical processes generally dominate during ultrasonic-induced
      degradation, pyrolysis appears to be responsible for a significant fraction of
      the observed degradation. Several pyrolytic products from MIB and GSM have been
      identified and degradation pathways are elucidated. The degradation of MIB and
      GSM follows the first-order kinetics and the rate constants are 0.07 and 0.12
      min(-1), respectively. These results suggest ultrasonic irradiation maybe
      applicable as an effective method for removal of taint compounds from potable
      water supplies and fish farms.

PMID- 17434559
TI  - Protein complexes associated with the Kaposi's sarcoma-associated herpesvirus
      encoded LANA.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the major biological cofactor
      contributing to development of Kaposi's sarcoma. KSHV establishes a latent
      infection in human B cells expressing the latency-associated nuclear antigen
      (LANA), a critical factor in the regulation of viral latency. LANA is known to
      modulate viral and cellular gene expression. We report here on some initial
      proteomic studies to identify cellular proteins associated with the amino and
      carboxy-terminal domains of LANA. The results of these studies show an
      association of known cellular proteins which support LANA functions and have
      identified additional LANA-associated proteins. These results provide new
      evidence for complexes involving LANA with a number of previously unreported
      functional classes of proteins including DNA polymerase, RNA helicase and cell
      cycle control proteins. The results also indicate that the amino terminus of LANA
      can interact with its carboxy-terminal domain. This interaction is potentially
      important for facilitating associations with other cell cycle regulatory proteins
      which include CENP-F identified in association with both the amino and carboxy
      termini. These novel associations add to the diversity of LANA functions in
      relation to the maintenance of latency and subsequent transformation of KSHV
      infected cells.

PMID- 17434561
TI  - Detection and genotyping of Giardia duodenalis in wastewater: relation between
      assemblages and faecal contamination origin.
AB  - Among the seven assemblages identified in Giardia duodenalis species, only
      assemblages A and B infect humans and numerous other mammals as well. On the
      other hand, assemblage E is considered to be host restricted to livestock. The
      aim of the present study was to compare the presence of G. duodenalis assemblages
      A, B and E in wastewater samples from two municipal treatment plants (n=24) and
      one slaughterhouse (n=12). Thus, PCR assays targeting the tpi gene were developed
      to detect specifically these three G. duodenalis assemblages. Assemblages A and B
      were detected in urban wastewater with a predominance of assemblage A, especially
      for one treatment plant. Concerning slaughterhouse wastewater, assemblage A was
      found in 58% of the samples, whereas assemblage B was not detected. Assemblage E
      was not detected in urban wastewater, but was found in 92% of the samples from
      slaughterhouse. Thus, combination of assemblages A and B seemed to indicate a
      human contamination origin, while combination of assemblages A and E appeared to
      correspond to a livestock contamination origin.

PMID- 17434562
TI  - Advances in enhanced biological phosphorus removal: from micro to macro scale.
AB  - The enhanced biological phosphorus removal (EBPR) process has been implemented in
      many wastewater treatment plants worldwide. While the EBPR process is indeed
      capable of efficient phosphorus (P) removal performance, disturbances and
      prolonged periods of insufficient P removal have been observed at full-scale
      plants on numerous occasions under conditions that are seemingly favourable for
      EBPR. Recent studies in this field have utilised a wide range of approaches to
      address this problem, from studying the microorganisms that are primarily
      responsible for or detrimental to this process, to determining their biochemical
      pathways and developing mathematical models that facilitate better prediction of
      process performance. The overall goal of each of these studies is to obtain a
      more detailed insight into how the EBPR process works, where the best way of
      achieving this objective is through linking together the information obtained
      using these different approaches. This review paper critically assesses the
      recent advances that have been achieved in this field, particularly relating to
      the areas of EBPR microbiology, biochemistry, process operation and process
      modelling. Potential areas for future research are also proposed. Although
      previous research in this field has undoubtedly improved our level of
      understanding, it is clear that much remains to be learned about the process, as
      many unanswered questions still remain. One of the challenges appears to be the
      integration of the existing and growing scientific knowledge base with the
      observations and applications in practice, which this paper hopes to partially
      achieve.

PMID- 17434563
TI  - Removal of diuron and amitrole from water under static and dynamic conditions
      using activated carbons in form of fibers, cloth, and grains.
AB  - This study investigated the removal of the herbicides diuron and amitrole from
      water under static and dynamic conditions using different activated carbons in
      the form of fibers, cloth, and grains. In all cases, there was much greater
      adsorption of diuron than of amitrole due to the lower solubility, greater
      hydrophobicity, and larger dipolar moment of the former. The activated carbon
      cloth was the best adsorbent for diuron under dynamic conditions because it had
      the largest mesopore volume, water-accessible pore volume, and surface area.
      However, the best adsorbent for amitrole under dynamic conditions was the
      granular activated carbon due to its higher surface basicity. Comparisons using
      the best adsorbent for each herbicide showed that diuron was removed by the
      activated carbon more efficiently compared with amitrole under both dynamic and
      static conditions.

PMID- 17434564
TI  - A thermodynamic analysis on adsorption of estrogens in activated sludge process.
AB  - The adsorption behaviors of estrone (E1), 17beta-estradiol (E2), estriol (E3), 17
      alpha-ethinylestradiol (EE2), and equol were studied with a deactivated sludge
      subjected to heat treatment at 80 degrees C for 30 min. The heat-treatment hardly
      changed the adsorption features of activated sludge (AS). The adsorption
      equilibrium of all estrogens was approached within 10 min at 20 degrees C, and a
      high removal of estrogens was achieved simultaneously. The equilibrium data were
      well fitted by a Freundlich isotherm. The adsorption behaviors of E1, E2, E3 and
      EE2 in the AS system were independent of their Kow values. Thermodynamic analysis
      revealed that the adsorption behaviors of E1, E2, E3 and EE2 could be considered
      as an exothermic, physical and reversible process, resulting in their higher
      adsorption capacities at lower temperature. Regarding equol, its adsorption was
      an endothermic, chemical and irreversible process.

PMID- 17434565
TI  - Natural organic matter (NOM) removal and structural changes in the bacterial
      community during artificial groundwater recharge with humic lake water.
AB  - This study evaluated the removal of natural organic matter (NOM) and structural
      changes in the microbial community during infiltration of humic lake water at
      three artificial groundwater recharge (AGR) sites in Finland. The three sites
      were at waterworks in Hameenlinna, Jyvaskyla and Tuusula, sites A, B and C,
      respectively. Site A used groundwater recharge by both basin and sprinkling
      infiltration, site B used only sprinkling infiltration, and site C used only
      basin infiltration. Reductions of total organic carbon at sites A, B and C were
      91%, 84% and 74%, respectively, in the winter, and 88%, 77% and 73%,
      respectively, in the summer. The Finnish national recommended value of 2 mg/l for
      TOC was achieved at all sites and the TOC of natural groundwater at site C was
      much lower, at 0.6 mg/l. Large molecular fractions of NOM were removed more
      efficiently than the smaller ones. Total amount of DAPI-stained cells decreased
      during infiltration at sites A, B and C in winter by 94%, 94% and 75% and in
      summer by 96%, 97% and 94%, respectively. Bacterial communities in raw waters and
      extracted groundwaters were diverse with changes occurring during infiltration,
      which was shown by DNA extraction followed by PCR of 16S rRNA genes and
      denaturing gradient gel electrophoresis (DGGE) fingerprinting. While the natural
      groundwater microbial community was diverse, it was different from that of the
      extracted groundwater in the AGR area. Simultaneous organic carbon removal and
      the decrease of bacterial counts during infiltration indicated biodegradation. In
      addition, the changing DGGE profiles during the process of infiltration,
      demonstrated that changing environmental conditions were reflected by changes in
      bacterial community composition.

PMID- 17434566
TI  - Assessment of the pollution impact on biomarkers of effect of a freshwater fish.
AB  - Changes in biomarkers of fish captured from stressed environments may represent a
      reliable tool in revealing sublethal effects of the pollutants found in aquatic
      ecosystems. The response patterns of selected biochemical and morphological
      variables biomarkers of effect were assessed in adult females of an indigenous
      teleost Cnesterodon decemmaculatus, caught at a polluted site (San Francisco) of
      the Reconquista river (Buenos Aires, Argentina). Combined field-caging
      experiments with controlled laboratory exposure to clean media were performed.
      The biochemical parameters measured were specific activities of gill (Na+ + K+)
      ATPase, liver AlaAT and AspAT, and brain AChE; LSI and CF were also calculated.
      The changes in gill (Na+ + K+)-ATPase and liver AlaAT activities of fish captured
      in the field in most cases were reversible after transfer to clean media. The
      results were interpreted in association with the physicochemical profile of the
      water samples taken simultaneously with the capture of the fish. Results
      suggested the suitability of the test species used as tools in environmental
      monitoring programs of risk assessment.

PMID- 17434567
TI  - Effects of temperature and dissolved oxygen on Se(IV) removal and Se(0)
      precipitation by Shewanella sp. HN-41.
AB  - Facultative anaerobic Shewanella sp. strain HN-41 was able to utilize selenite
      (Se(IV)) as a sole electron acceptor for respiration in anaerobic condition,
      resulting in reduction of Se(IV) and then precipitation of elemental Se nano
      sized spherical particles, which were identified using energy-dispersive X-ray
      spectroscopy and X-ray absorption near-edge structure spectroscopy. When the
      effects on Se(IV) reduction to elemental Se were studied by varying incubation
      temperatures and dissolved oxygen contents, Se(IV) reduction occurred more
      actively with higher removal rate of Se(IV) in aqueous phase and well-shaped
      spherical Se(0) nanoparticles were formed from the incubations under N(2) (100%)
      or N(2):O(2) (80%:20%) at 30 degrees C with average diameter values of 181+/-40
      nm and 164+/-24 nm, respectively, while relatively less amounts of irregular
      shaped Se(0) nanoparticles were produced with negligible amount of Se(IV)
      reduction and removal under 100% of O(2). The Se particle size distributions
      based on scanning electron microscopy also showed a general tendency towards
      decreased Se particle size as oxygen content increased, whereas the particle size
      seemed uncorrelated to the change in the incubation temperature. These results
      also suggest that the size-controlled biological Se(0) nanospheres production may
      be achieved simply by changing the culture conditions.

PMID- 17434568
TI  - Interaction of bioaccumulation of heavy metal chromium with water relation,
      mineral nutrition and photosynthesis in developed leaves of Lolium perenne L.
AB  - Contamination by chromium (Cr) is widespread in agricultural soils and industrial
      sites. This heavy metal represents a risk to human health. In order to gain
      fundamental insights into the nature of the adaptation to Cr excess, the
      characterisation of physiological indices, including responses of photosynthetic
      gas exchange and chlorophyll a fluorescence along with changes in mineral
      nutrient contents and water status were studied in ray grass (Lolium perenne L.).
      Increased concentrations of Cr(VI) (0-500 microM Cr) in the Coic and Lessaint
      nutrient solution were applied. The growth of Lolium perenne is decreased by
      chromium and the leaves have lost their pigments. Chromium accumulation was
      greater in roots than in leaves and reached 2450 and 210 microg g(-1) DW,
      respectively with 500 microM Cr(VI) in nutrient medium. The physiological
      parameters were severely reduced by this heavy metal. Cr induced toxicity arising
      from 100 microM Cr(VI) and resulted in a modification of mineral content in roots
      and leaves, especially for Ca, Mg and Fe. The chromium stress decreased CO2
      assimilation rates mainly due to stomatal closure, which reduced water loss by
      transpiration without decreasing the cellular available CO2. The fluorescence
      parameters associated with photosystem II (PSII) activity and the photochemical
      activity are modified by chromium. Non-radiative energy dissipation mechanisms
      were triggered during stress since non-photochemical quenching was increased and
      efficiency of excitation capture by open centers was reduced.

PMID- 17434569
TI  - Predicting radium availability and uptake from soil properties.
AB  - The results of a potted soil experiment to determine the soil and plant factors
      ruling radium availability and uptake by ryegrass and clover are described. Nine
      soils with distinct soil characteristics were spiked with 226 Ra. They were
      thoroughly characterized and the solid liquid partitioning coefficient, Kd, was
      determined. Kd ranged from 38 l kg(-1) to 446 l kg(-1) (average: 188+/-156 l kg(
      1)) and was linearly related to cation exchange capacity (CEC) and organic matter
      (OM) content. The soil-to-plant transfer factor (TF) was significantly affected
      by the chemical properties of the soils and ranged from 0.054 kg kg(-1) to 0.719
      kg kg(-1) for ryegrass and from 0.034 kg kg(-1) to 1.494 kg kg(-1) for clover.
      Overall, no significant difference in TF between ryegrass and clover was
      observed. TF was related to Kd, to CEC, OM (for ryegrass only when excluding one
      soil) and the calcium concentration in the soil solution (for both plants if
      excluding one soil). Radium flux were calculated from the radium concentration in
      the soil solution and the evapotranspiration, to predict total radium uptake
      derived from shoot radium concentration and biomass yield. It was found that
      radium uptake could be predicted from the radium flux (R2=0.61 and 0.83 for
      ryegrass and clover, respectively). Higher predictability (R2=0.70 and 0.91 for
      ryegrass and clover, respectively) was obtained when relating total radium uptake
      to a radium flow considering competition effects at the root surface by bivalent
      cations.

PMID- 17434570
TI  - Acid-base properties of humic substances from composted and thermally-dried
      sewage sludges and amended soils as determined by potentiometric titration and
      the NICA-Donnan model.
AB  - The acid-base properties of humic acids (HAs) and fulvic acids (FAs) isolated
      from composted sewage sludge (CS), thermally-dried sewage sludge (TS), soils
      amended with either CS or TS at a rate of 80 t ha(-1)y(-1) for 3y and the
      corresponding unamended soil were investigated by use of potentiometric
      titrations. The non-ideal competitive adsorption (NICA)-Donnan model for a
      bimodal distribution of proton binding sites was fitted to titration data by use
      of a least-squares minimization method. The main fitting parameters of the NICA
      Donnan model obtained for each HA and FA sample included site densities, median
      affinity constants and widths of affinity distributions for proton binding to low
      and high affinity sites, which were assumed to be, respectively, carboxylic- and
      phenolic-type groups. With respect to unamended soil HA and FA, the HAs and FAs
      from CS, and especially TS, were characterized by smaller acidic functional group
      contents, larger proton binding affinities of both carboxylic- and phenolic-type
      groups, and smaller heterogeneity of carboxylic and phenolic-type groups.
      Amendment with CS or TS led to a decrease of acidic functional group contents and
      a slight increase of proton binding affinities of carboxylic- and phenolic-type
      groups of soil HAs and FAs. These effects were more evident in the HA and FA
      fractions from CS-amended soil than in those from TS-amended soil.

PMID- 17434571
TI  - Homoplasy and homology: dichotomy or continuum?
AB  - Homology is the presence of the same feature in two organisms whose most recent
      common ancestor also possessed the feature. I discuss the bases on which we can
      tell that two features being compared share sufficient elements of sameness to
      allow them to be treated as homologous and therefore to be legitimately compared
      with one another in a way that informs comparative, evolutionary, and
      phylogenetic analysis. To do so, I discuss the relationship(s) between homology
      and homoplasy to conclude that we are dealing neither with a dichotomy between
      homoplasy as parallelism/convergence and homology as common descent nor with a
      dichotomy of homoplasy as the interrupted presence of the character in a lineage
      and homology as the continuous presence of the character. Rather, we are dealing
      with common descent with varying degrees of modification. Homoplasy and homology
      are not dichotomies but the extremes of a continuum, reflecting deep or more
      recent shared ancestry based on shared cellular mechanisms and processes and
      shared genes and gene pathways and networks. The same genes can be used to
      initiate the development of homoplastic and homologous structures. Consequently,
      structures may be lost but their developmental bases retained, providing the
      potential for homoplasy. It should not be surprising that similar features
      persist when a feature is present in the nearest common ancestor (homology).
      Neither should it be surprising to find that different environments or selective
      pressures can trigger the reappearance of similar features in organisms that do
      not share a recent common ancestor (homoplasy).

PMID- 17434573
TI  - Taking phylogenetics beyond pattern analysis: can models of genome dynamics guide
      predictions about homoplasy in morphological and behavioral data sets?
AB  - Despite the considerable amount of interest in phylogeny reconstruction, patterns
      of homoplasy in morphological and behavioral data have received only limited
      attention to date, whereas the patterns of homoplasy in molecular data are
      relatively well understood. First, because the number of alternative molecular
      character states is strictly limited (particularly for nucleotide sequence data),
      higher rates of substitution generate higher levels of homoplasy. Second,
      depending on the relative proportions of constrained and unconstrained sites,
      each molecular data set has a time frame of applicability outside of which
      resolution becomes ambiguous. There is good evidence to suggest that numbers of
      alternative character states for morphological and even behavioral data may be
      similarly limited and that higher rates of evolution are often linked to higher
      rates of homoplasy. Like molecular data sets, morphological and behavioral data
      sets contain rapidly evolving characters as well as more conservative elements.
      Morphologies and behaviors related to sexual recognition and reproduction show
      low levels of intraspecific variation, but high levels of lability between
      species, making them crucial for species identification but often poor as markers
      of relationship at greater time depths. The organization theory of speciation
      derived by Carson is a model based on genome dynamics, and it predicts exactly
      this window of applicability for characters related to sexual reproduction.
      Nonsexual characters related to environmental adaptation should be applicable at
      greater phylogenetic depths. A better understanding of patterns of homoplasy
      enables a more sophisticated approach to the assessment of the relative
      reliabilities of alternative tree topologies.

PMID- 17434574
TI  - How to identify (as opposed to define) a homoplasy: examples from fossil and
      living great apes.
AB  - There is much debate on the definitions of homoplasy and homology, and on how to
      spot them among character states used in a phylogenetic analysis. Many advocate
      what I call a "processual approach," in which information on genetics,
      development, function, or other criteria help a priori in identifying two
      character states as homologous or homoplastic. I argue that the processes
      represented by these criteria are insufficiently known for most organisms and
      most characters to be reliably used to identify homoplasies and homologies.
      Instead, while not foolproof, phylogeny should be the ultimate test for homology.
      Character states are assumed to be homologous a priori because this is
      falsifiable and because their initial inclusion in the character-state analysis
      is based on the assumption that they may be phylogenetically informative. If they
      fall out as symplesiomorphies or synapomorphies in a phylogenetic analysis, their
      status as homologies remains unfalsified. If they fall out as homoplasies, having
      evolved independently in more than one clade, their status as homologous is
      falsified, and a homoplasy is identified. The character-state transformation
      series, functional morphology, finer levels of morphological comparison, and the
      distribution and correlation of characters all help to explain the presence of
      homoplasies in a given phylogeny. Explaining these homoplasies, and not ignoring
      them as "noise," should be as much a goal of phylogenetic analysis as the
      production of a phylogeny. Examples from the fossil record of Miocene hominoids
      are given to illustrate the advantages of a process-informs-pattern-recognition
      after-the-fact approach to understanding the evolution of character states.

PMID- 17434575
TI  - Development of a site-specific Ecological Risk Assessment for contaminated sites:
      part II. A multi-criteria based system for the selection of bioavailability
      assessment tools.
AB  - A comparison procedure based on Multi-Criteria Decision Analysis (MCDA) and
      expert judgment was developed in order to allow the comparison of bioavailability
      tests to implement the chemical Line of Evidence (LoE) within a TRIAD based site
      specific Ecological Risk Assessment framework including three tires of
      investigation. The proposed methodology was included in the Module 1 of the
      Decision Support System DSS-ERAMANIA and the obtained rank supported the
      selection of a suitable set of available tests to be applied to the case study. A
      simplified application of the proposed procedure is described and results
      obtained by the system software are discussed.

PMID- 17434576
TI  - Indoor air quality in a dentistry clinic.
AB  - The purpose of this work is to assess, both experimentally and theoretically the
      status of air quality in a dentistry clinic of the Athens University Dentistry
      Faculty with respect to chemical pollutants and identify the indoor sources
      associated with dental activities. Total VOCs, CO(2), PM(10), PM(2.5), NO(x) and
      SO(2) were measured over a period of approximately three months in a selected
      dentistry clinic. High pollution levels during the operation hours regarding
      CO(2), total VOCs and Particulate Matter were found, while in the non-working
      periods lower levels were recorded. On the contrary, NO(x) and SO(2) remained at
      low levels for the whole experimental period. These conditions were associated
      with the number of occupants, the nature of the dental clinical procedures, the
      materials used and the ventilation schemes, which lead to high concentrations,
      far above the limits that are set by international organizations and concern
      human exposure. The indoor environmental conditions were investigated using the
      Computational Fluid Dynamics (CFD) model PHOENICS for inert gases simulation. The
      results revealed diagonal temperature stratification and low air velocities
      leading to pollution stratification, accompanied by accumulation of inert gaseous
      species in certain areas of the room. Different schemes of natural ventilation
      were also applied in order to examine their effect on the indoor comfort
      conditions for the occupants, in terms of air renewal and double cross
      ventilation was found to be most effective. The relative contribution of the
      indoor sources, which are mainly associated with indoor activities, was assessed
      by application of the Multi Chamber Indoor Air Quality Model (MIAQ) to the
      experimental data. It was found that deposition onto indoor surfaces is an
      important removal mechanism while a great amount of particulate matter emitted in
      the Clinic burdened severely the indoor air quality. The natural ventilation of
      the room seemed to reduce the levels of the fine particles. The emission rates
      for the fine and coarse particulates were found to be almost equal, while the
      coarse particles were found susceptible to deposition onto indoor surfaces.

PMID- 17434577
TI  - Pre-admission warfarin use in patients with acute ischemic stroke and atrial
      fibrillation: The appropriate use and barriers to oral anticoagulant therapy.
AB  - INTRODUCTION: Warfarin reduces the risk of stroke in patients with atrial
      fibrillation. Despite strong guideline recommendations, studies continue to
      demonstrate the under-use of warfarin in clinical practice. PURPOSE: To determine
      the prevalence and predictors of warfarin use in patients presenting with atrial
      fibrillation and acute ischemic stroke who do not have a documented
      contraindication to anticoagulants. METHODS: We conducted a retrospective chart
      review of all patients admitted to the Hamilton General Hospital with a primary
      diagnosis of ischemic stroke and a coded diagnosis of atrial fibrillation between
      1999 and 2004. Using a standardized data abstraction form, the following
      variables were recorded: baseline demographics, past medical history including
      risk factors for stroke and major bleeding and known predictors of warfarin under
      use. In cases where warfarin was not prescribed, charts were also reviewed for
      documented contraindications to warfarin use. The following were considered valid
      contraindications to warfarin: patient refusal, non-compliance with INR
      monitoring, bleeding diathesis, history of major bleeding or significant alcohol
      consumption. RESULTS: In total, 196 patients with ischemic stroke and atrial
      fibrillation were identified. Of these patients, 106 were considered to be
      appropriate candidates for anticoagulation after excluding patients with no known
      diagnosis of atrial fibrillation prior to admission (N=59), a valid
      contraindication to warfarin use (N=18), a CHADS2 score <1 (N=6) or a competing
      diagnosis for warfarin use (N=7). Of the patients deemed to be suitable
      candidates for warfarin, 57 (54%) were receiving warfarin therapy on admission.
      On multivariable analyses, increasing age (OR 0.7; 95% CI 0.5-0.9) was associated
      with a reduced odds of warfarin use while a history of stroke or TIA (OR 2.6; 95%
      CI 1.1-6.5) and a history of congestive heart failure (OR 3.2; 95% CI 1.1-9.0)
      were associated with an increased odds of warfarin use in patients without a
      contraindication to warfarin. While 75% of patients <75 years old were
      anticoagulated, only 33% of those >85 years were prescribed warfarin on admission
      to hospital. CONCLUSIONS: early half of all patients presenting with atrial
      fibrillation and acute ischemic stroke who were suitable candidates for
      anticoagulation were not prescribed warfarin. In patients not prescribed
      warfarin, very few had a documented contraindication. Advanced age appears to be
      the strongest predictor of warfarin non-use.

PMID- 17434578
TI  - The relation between nicotinamide N-methyltransferase gene polymorphism and
      plasma homocysteine concentration in healthy Japanese men.

PMID- 17434579
TI  - Secondary cytoreduction in the management of recurrent uterine leiomyosarcoma.
AB  - OBJECTIVES: To identify effective treatment options for patients with recurrent
      uterine leiomyosarcoma (LMS). METHODS: Patients with uterine LMS treated between
      1976 and 1999 were identified. Charts were retrospectively reviewed and relevant
      clinical and pathologic data extracted. Survival curves were generated using the
      methods of Kaplan and Meier. Multivariate analysis was performed using the Cox
      proportional model. RESULTS: Chart review identified 128 patients with recurrent
      uterine LMS. The median time to recurrence was 1.3 years. The median disease
      specific survival from the time of first recurrence was 1.8 years. Multivariate
      analysis demonstrated secondary cytoreductive surgery, prolonged time to
      recurrence and localized recurrence were significantly and independently
      associated with improved disease-specific survival from time of first recurrence.
      Neither chemotherapy nor radiation therapy was associated with improvement in
      outcome in patients with recurrent uterine LMS. CONCLUSIONS: These data suggest
      that secondary cytoreductive surgery is associated with prolonged survival in a
      select group of patients with recurrent uterine LMS. Patients presenting after a
      prolonged progression-free interval with an isolated site of recurrence amenable
      to complete resection are the best candidates for attempted surgical resection.
      These findings require confirmation from a larger and preferably prospectively
      gathered database.

PMID- 17434580
TI  - The effect of three-dimensional demineralized bone matrix on in vitro cumulus
      free oocyte maturation.
AB  - The physiological role of cumulus cell surrounding oocytes is particularly
      important for normal cytoplasmic maturation of oocytes. Collagen-based
      demineralized bone matrix (DBM) is a valuable biomaterial for the three
      dimensional (3-D) cell culture. The present study was designed to determine
      whether in vitro maturation (IVM) of cumulus-free oocytes in mice could be
      improved by using the 3-D DBM co-culture system. The results indicated that the
      denuded oocytes cultured in 3-D DBM co-culture system with cumulus cells showed
      close similarity of cortical granules (CGs) distribution pattern, had more normal
      maturation-promoting factor (MPF) level and zona pellucida (ZP) hardening level
      to the in vivo matured oocytes, and the best preimplantation development after
      being activated by in vitro fertilization (IVF) or parthenogenetic activation.
      Thus, 3-D DBM collagen scaffold could serve as a tool for fundamental in vitro
      studies of cells or tissues under the environment that closely assembles the in
      vivo conditions.

PMID- 17434581
TI  - A novel trans-lymphatic drug delivery system: implantable gelatin sponge
      impregnated with PLGA-paclitaxel microspheres.
AB  - A translymphatic drug delivery system which incorporates poly-lactide-co
      glycolide-paclitaxel (PLGA-PTX) or PLGA-rhodamine microspheres into gelatin
      sponge matrix is described. The system combines the sustained release properties
      of PLGA-PTX with the structural advantages of gelatin matrix that can be
      implanted directly to the lymphatic site for both therapeutic and prophylactic
      purposes. The PLGA microspheres were prepared using spray drying technique. The
      particles were in the size range of 1-8 microm, suitable for intraperitoneal and
      intrapleural lymphatic targeting delivery. Scanning electron microscopy revealed
      the homogeneous distribution of PLGA microspheres in the porous sponge network.
      The release of PTX was mainly controlled by the degradation of the PLGA.
      Crosslinking gelatin using carbodiimide reduced the biodegradation of the sponge
      and thereby delayed the release of the PLGA in vitro. In vivo lymphatic delivery
      was assessed in both healthy rats and rats bearing orthotopic lung cancer.
      Intraperitoneal and intrapleural implantation of the sponge impregnated with PLGA
      microspheres resulted in spontaneous absorption of the particles in the lymphatic
      system. It is concluded that the system provides great potential for targeted
      delivery of therapeutic agent to the lymphatic system especially for the control
      of lymphatic metastasis in cancer.

PMID- 17434583
TI  - What does over-expression of cN-II enzyme signify in haematological malignancies?

PMID- 17434582
TI  - Cell patterning chip for controlling the stem cell microenvironment.
AB  - Cell-cell signaling is an important component of the stem cell microenvironment,
      affecting both differentiation and self-renewal. However, traditional cell
      culture techniques do not provide precise control over cell-cell interactions,
      while existing cell-patterning technologies are limited when used with
      proliferating or motile cells. To address these limitations, we created the Bio
      Flip Chip (BFC), a microfabricated polymer chip containing thousands of
      microwells, each sized to trap down to a single stem cell. We have demonstrated
      the functionality of the BFC by patterning a 50 x 50 grid of murine embryonic
      stem cells (mESCs), with patterning efficiencies >75%, onto a variety of
      substrates--a cell-culture dish patterned with gelatin, a 3-D substrate, and even
      another layer of cells. We also used the BFC to pattern small groups of cells,
      with and without cell-cell contact, allowing incremental and independent control
      of contact-mediated signaling. We present quantitative evidence that cell-cell
      contact plays an important role in depressing mESC colony formation, and show
      that E-cadherin is involved in this negative regulatory pathway. Thus, by
      allowing exquisite control of the cellular microenvironment, we provide a
      technology that enables new applications in tissue engineering and regenerative
      medicine.

PMID- 17434584
TI  - Multicopy plasmid modification with phage lambda Red recombineering.
AB  - Recombineering, in vivo genetic engineering using the bacteriophage lambda Red
      generalized recombination system, was used to create various modifications of a
      multicopy plasmid derived from pBR322. All genetic modifications possible on the
      Escherichia coli chromosome and on bacterial artificial chromosomes (BACs) are
      also possible on multicopy plasmids and are obtained with similar frequencies to
      their chromosomal counterparts, including creation of point mutations (5-10%
      unselected frequency), deletions and substitutions. Parental and recombinant
      plasmids are nearly always present as a mixture following recombination, and
      circular multimeric plasmid molecules are often generated during the
      recombineering.

PMID- 17434585
TI  - Effects of organohalogen pollutants on haematological and urine clinical-chemical
      parameters in Greenland sledge dogs (Canis familiaris).
AB  - Seven West Greenland sledge dog bitches (Canis familiaris) and their three pups
      were fed 50-200 g of contaminated West Greenland minke whale (Balaenoptera
      acutorostrata) blubber, and in a control cohort eight sister bitches and their
      five pups were fed a similar amount pork fat. Blood plasma and urine clinical
      chemical parameters were measured and compared between the bitches and pups form
      the control and exposed cohorts. Based on existing reference intervals, Arctic
      mammals may have blood clinical-chemical endpoint levels that differ from
      comparable species at lower latitudes. The cortisol:creatinine ratio,
      protein:creatinine ratio, alkaline phosphatase, cholesterol and inorganic
      phosphate were significantly highest (ANCOVA: all p<0.05) in the pup generation.
      The cortisol:creatinine ratio, cholesterol, lactate dehydrogenase and creatinine
      kinase were significantly higher (ANCOVA: all p<0.05) in the control group, while
      glucose was significantly highest (ANCOVA: p<0.05) in the exposed group.
      Furthermore, the blood cholesterol levels indicate that exposure via the diet to
      marine mammal blubber has a preventive effect on the development of
      cardiovascular diseases. We therefore suggest that the consumption of
      contaminated Arctic marine blubber impacted liver and kidney function in adult
      and pup sledge dogs.

PMID- 17434586
TI  - Effects of Pediococcus- and Saccharomyces-based probiotic (MitoMax) on
      coccidiosis in broiler chickens.
AB  - Coccidiosis is the major parasitic disease of poultry. In this study, the role of
      the commercial probiotic MitoMax which contains Pediococcus acidilactici and
      Saccharomyces boulardii was evaluated by measuring body weight gain, fecal oocyst
      shedding, and serum antibody responses as an alternative control method of
      prophylactic drug against coccidiosis. Day-old broiler chicks were fed regular or
      probiotic diets supplemented with MitoMax at 0.01%, 0.1%, or 1.0% of diet, and
      challenged 2 weeks later with 5000 oocysts of either Eimeria acervulina (EA) or
      Eimeria tenella (ET). Birds fed 1.0% or 0.1% MitoMax-supplemented diets in EA- or
      ET-infected groups shed less (P<0.05) oocysts than control-infected chickens.
      Also, chickens fed 0.1% MitoMax-supplemented diet and infected with EA exhibited
      higher (P<0.001) serum Eimeria-specific antibodies than other groups. These
      results demonstrate that MitoMax may enhance the resistance of birds against
      coccidiosis by enhancing humoral immunity when included at > or = 0.1% of the
      broiler diet.

PMID- 17434587
TI  - Effects of prior knowledge and expert statement on belief in recovered memories:
      an international perspective.
AB  - We tested the hypothesis that beliefs in the purported attributes of recovered
      memories of child sexual abuse (CSA) are associated with knowledge of the
      "recovered/false memory debate", and that such beliefs will be related to
      assessments of the credibility of statements made by participants in a vignette
      about CSA. Participants from five countries (the United States, Canada, New
      Zealand, the United Kingdom and Israel) responded to a questionnaire regarding
      beliefs about recovered memory as well as self-reported exposure to and knowledge
      of the debate. In addition, they assessed the credibility of statements made by a
      daughter (reporting recovery of memories of sexual abuse by her father), her
      father (denying the allegation and accusing the daughter's therapist of
      implanting in her false "memories" of abuse), and two experts (each supporting
      one of the two protagonists). We found that prior knowledge of the debate across
      countries was linked to beliefs in specific attributes of recovered memories and
      to a subset of the credibility assessments of statements made by the protagonists
      and their experts. For individuals, however, credibility assessments were
      unrelated to knowledge of the debate, but they were related to beliefs about
      memory recovery. Finally, credibility of the protagonists' statements was
      differentially associated with those made by the daughter's and the father's
      experts. The results suggest that whereas familiarity with the debate does not
      affect the credibility of the statements made by the complainant and the accused,
      expert testimony does, as has been found in prior research. The psycholegal
      implications of this conclusion are discussed.

PMID- 17434588
TI  - Punctate inner choroidopathy: a survey analysis of 77 persons.
AB  - PURPOSE: To evaluate the demographic and clinical features of punctate inner
      choroidopathy (PIC). DESIGN: Noncomparative survey. PARTICIPANTS: Persons with
      PIC who were in contact with the PIC Society. METHODS: A survey was designed and
      posted on the Web site of the PIC Society, and persons diagnosed with PIC were
      invited to participate. Seventy-seven persons with PIC completed the survey. MAIN
      OUTCOME MEASURES: Demographics, presenting symptoms, disease manifestations,
      treatment regimens, and ocular complications. RESULTS: Of the 77 participants who
      completed the survey, 90% were women, 97% Caucasian, and 85% myopic. The median
      age of participants was 30 years (range, 15-55). The median duration of disease
      at the time of survey completion was 3 years (range, <1-14). Reported presenting
      symptoms of PIC included scotomata (91%), blurred vision (86%), photopsias (73%),
      floaters (69%), photophobia (69%), metamorphopsia (65%), and loss of peripheral
      vision (26%). Eighty-five percent reported unilateral scotomata initially. Thirty
      two percent of participants reported waxing and waning symptoms before treatment.
      The majority of participants (86%) had received treatment, most commonly with
      systemic (60%) and/or intraocular corticosteroids (22%). Fourteen percent of
      participants reported treatment with at least one immunosuppressive agent at some
      time during their disease. Sixty-nine percent had been diagnosed with choroidal
      neovascularization and 56% with subretinal fibrosis in at least one eye. In 75%
      of respondents, the onset of choroidal neovascularization occurred less than 1
      year after the presenting symptoms of PIC, and in 79%, the onset of subretinal
      fibrosis occurred less than 1 year after the presenting symptoms. CONCLUSIONS: In
      this survey of 77 persons with PIC, the majority of respondents were young,
      myopic, Caucasian women, who experienced unilateral scotoma and blurred vision as
      initial symptoms. The ocular complications choroidal neovascularization and
      subretinal fibrosis were present in the majority of participants in at least one
      eye and typically occurred within the first year of initial symptoms.

PMID- 17434589
TI  - The quality of reporting of diagnostic accuracy studies of optical coherence
      tomography in glaucoma.
AB  - OBJECTIVE: To evaluate the quality of reporting of diagnostic accuracy studies
      using optical coherence tomography (OCT) in glaucoma. DESIGN: Descriptive series
      of published studies. PARTICIPANTS: Published studies reporting a measure of the
      diagnostic accuracy of OCT for glaucoma. METHODS: Review of English language
      papers reporting measures of diagnostic accuracy of OCT for glaucoma. Papers were
      identified from a Medline literature search performed in June 2006. Articles were
      appraised using the 25 items provided by the Standards for Reporting of
      Diagnostic Accuracy (STARD) initiative. Each item was recorded as full,
      partially, or not reported. MAIN OUTCOME MEASURES: Degree of compliance with the
      STARD guidelines. RESULTS: Thirty papers were appraised. Eight papers (26.7%)
      fully reported more than half of the STARD items. The lowest number of fully
      reported items in a study was 5 and the highest was 17. Descriptions of key
      aspects of methodology frequently were missing. For example, details of
      participant sampling (e.g., consecutive or random selection) were described in
      only 8 (26.7%) of 30 publications. Measures of statistical uncertainty were
      reported in 18 (60%) of 30 publications. No single STARD item was fully reported
      by all the papers. CONCLUSIONS: The standard of reporting of diagnostic accuracy
      studies in glaucoma using OCT was suboptimal. It is hoped that adoption of the
      STARD guidelines will lead to an improvement in reporting of diagnostic accuracy
      studies, enabling clearer evidence to be produced for the usefulness of OCT for
      the diagnosis of glaucoma.

PMID- 17434590
TI  - Meningitis due to Streptococcus suis with no contact with pigs or porcine
      products.

PMID- 17434591
TI  - Sinusitis complicated by dural sinus thrombosis and Streptococcus pneumoniae
      endocarditis: a case report and review of the literature.
AB  - Streptococcus pneumoniae endocarditis is most commonly associated with pneumonia.
      It is relatively uncommon disease but its severity makes it clinically relevant.
      We present a case and review of sinusitis complicated by both pneumococcal
      endocarditis and cavernous sinus thrombosis. Both endocarditis and dural sinus
      thrombosis are known complications of facial infections. To our knowledge, this
      is the first reported case of both S. pneumoniae endocarditis and dural sinus
      thrombosis complicating sinusitis. A case report and review of the literature is
      presented.

PMID- 17434592
TI  - The olfactory granule cell: from classical enigma to central role in olfactory
      processing.
AB  - The granule cell of the olfactory bulb was first described by Golgi in 1875 and
      Cajal and his contemporaries in the 1890s as an enigmatic cell without an axon,
      whose status as a nerve cell was questionable. Insight into its functions began
      in the 1960s with evidence that it acted as an interneuron to mediate powerful
      inhibition of mitral cells. The circuit was found to involve dendrodendritic
      synapses for activation by mitral cell lateral dendrites of the granule cell
      dendritic spines and inhibition of the same and neighboring mitral cell lateral
      dendrites. Subsequent studies established the roles of glutamatergic receptors
      and GABAergic receptors in this circuit. The lateral inhibition is believed to be
      involved in contrast enhancement between mitral cells responding to different
      odor molecules. Current studies are analysing how the lateral inhibition can be
      mediated over arbitrary distances between columns of granule cells through action
      potential propagation in the mitral cell secondary dendrites. Among other
      important properties, granule cells undergo neurogenesis from precursor cells
      throughout adult life. This originally enigmatic cell thus appears to play a
      critical role in olfactory processing.

PMID- 17434593
TI  - A modified method for the detection of microbial proteases on agar plates using
      tannic acid.
AB  - In routine assay for the screening of microbes producing proteases, 10%
      trichloroaceticacid (TCA) is flooded on the milk agar plates after inoculation
      and required incubation to precipitate the protein. However, the clarity of the
      hydrolyzed zone is not very sharp and distinct. We herein present an improved
      assay for detecting the presence of extracellular protease from microorganisms on
      agar plates. In this method 10% tannic acid is flooded on the milk agar plate (in
      place of, TCA) to observe the zone of hydrolysis. Tannic acid sharply increases
      the colour intensity of the plate, as it favours the precipitation of the
      unhydrolyzed protein in the plate, thereby improving the contrast between the
      intact zones and the enzymatic lyses zones of the substrate. Our results indicate
      that this method is useful to detect extracellular proteases produced by both
      fungi as well as bacteria. The method used in the present study is sensitive, and
      can be easily performed for screening of large number of microbial cultures. This
      is the first report on the use of tannic acid for the detection of microbial
      proteases.

PMID- 17434594
TI  - Direct electrochemistry of hemoglobin in the hyaluronic acid films.
AB  - Hemoglobin (Hb) in the hyaluronic acid (HA) was cast at pyrolytic graphite (PG)
      electrodes for researching its electrochemical and electrocatalytic properties.
      The formal potential and electron transfer rate constant of Hb on HA films were
      determined, and the stability of the films, the pH effect, and the influence of
      supporting electrolyte concentrations upon Hb electrochemistry on the films were
      investigated by cyclic voltammetry and square wave voltammetry. UV-Vis absorption
      and reflectance absorption infrared (RAIR) spectra showed that the protein on HA
      film retained near-native secondary structure. The stable Hb-HA/PG gave
      analytically useful electrochemical catalytic responses to hydrogen peroxide.
      Thus, the property of the HA film for sorption and retention of water maybe
      utilized to develop some new biosensors.

PMID- 17434595
TI  - RNAi depleted Drosophila cell extracts to dissect signaling pathways leading to
      actin polymerization.
AB  - Dissection of signal transduction pathways leading to actin polymerization has
      been performed in cytosolic extracts. In such assays, the implication of an
      effector molecule is demonstrated by the loss of actin polymerization upon its
      depletion and the restoration of actin polymerization upon its add-back. Two
      major limitations in the wide use of this approach have been the availability of
      immunodepleting antibodies and the functional redundancy for many classes of
      effector molecules encoded by vertebrate genomes. To circumvent these
      limitations, we developed extracts derived from S2 Drosophila cells, which are
      competent for actin polymerization. In this system, depleted extracts are simply
      obtained from cells cultured with long double stranded RNAs in the medium. We
      validated the method by showing that beads coated with the C-terminal domain of
      Wave2 were no longer able to trigger actin polymerization in an extract depleted
      of the Arp2/3 complex. We also examined the complete set of Drosophila small
      GTPases of the Rho family for their ability to polymerize actin in such extracts,
      and found that only dCdc42 was able to induce actin polymerization. Using RNAi
      depleted extract, we confirmed that dCdc42 triggers actin polymerization in a
      Wasp dependent manner.

PMID- 17434596
TI  - Abnormal brain processing of affective and sensory pain descriptors in chronic
      pain patients.
AB  - OBJECTIVE: Previous research has suggested that chronic pain patients might be
      particularly vulnerable to the effects of negative mood during information
      processing. However, there is little evidence for abnormal brain processing of
      affective and sensory pain-related information in chronic pain. Behavioral and
      brain responses, to pain descriptors and pleasant words, were examined in chronic
      pain patients and healthy controls during a self-endorsement task. METHODS:
      Eighteen patients with fibromyalgia (FM), 18 patients with chronic
      musculoskeletal pain due to identifiable physical injury (MSK), and 16 healthy
      controls were asked to decide whether word targets described their current or
      past experience of pain. The number of self-endorsed words, elapsed time to
      endorse the words, and event-related potentials (ERPs) elicited by words, were
      recorded. RESULTS: Data revealed that chronic pain patients used more affective
      and sensory pain descriptors, and were slower in responding to self-endorsed pain
      descriptors than to pleasant words. In addition, it was found that affective pain
      descriptors elicited significantly more enhanced positive ERP amplitudes than
      pleasant words in MSK pain patients; whereas sensory pain descriptors elicited
      greater positive ERP amplitudes than affective pain words in healthy controls.
      CONCLUSIONS: These data support the notion of abnormal information processing in
      chronic pain patients, which might be characterized by a lack of dissociation
      between sensory and affective components of pain-related information, and by an
      exaggerated rumination over word meaning during the encoding of self-referent
      information about pain.

PMID- 17434598
TI  - Evaluation of diagnostic criteria for panic attack using item response theory:
      findings from the National Comorbidity Survey in USA.
AB  - BACKGROUND: The dichotomous diagnostic systems such as the Diagnostic and
      Statistical Manual of Mental Disorders (DSM) and International Classification of
      Diseases (ICD) lose much important information concerning what each symptom can
      offer. This study explored the characteristics and performances of DSM-IV and ICD
      10 diagnostic criteria items for panic attack using modern item response theory
      (IRT). METHODS: The National Comorbidity Survey used the Composite International
      Diagnostic Interview to assess 14 DSM-IV and ICD-10 panic attack diagnostic
      criteria items in the general population in the USA. The dimensionality and
      measurement properties of these items were evaluated using dichotomous factor
      analysis and the two-parameter IRT model. RESULTS: A total of 1213 respondents
      reported at least one subsyndromal or syndromal panic attack in their lifetime.
      Factor analysis indicated that all items constitute a unidimensional construct.
      The two-parameter IRT model produced meaningful and interpretable results. Among
      items with high discrimination parameters, the difficulty parameter for
      "palpitation" was relatively low, while those for "choking," "fear of dying" and
      "paresthesia" were relatively high. Several items including "dry mouth" and "fear
      of losing control" had low discrimination parameters. LIMITATIONS: The item
      characteristics of diagnostic criteria among help-seeking clinical populations
      may be different from those that we observed in the general population and
      deserve further examination. CONCLUSIONS: "Paresthesia," "choking" and "fear of
      dying" can be thought to be good indicators of severe panic attacks, while
      "palpitation" can discriminate well between cases and non-cases at low level of
      panic attack severity. Items such as "dry mouth" would contribute less to the
      discrimination.

PMID- 17434597
TI  - Does first episode polarity predict risk for suicide attempt in bipolar disorder?
AB  - BACKGROUND: Defining bipolar disorder (BD) subtypes with increased risk of
      suicidal behavior may help clinical management. We tested the hypothesis that the
      polarity of a patient's first mood episode would be a marker for BD subtypes with
      differential risk for suicidality. METHODS: One hundred thirteen subjects with
      DSM-IV defined BD were classified based on whether their first reported episode
      was manic/hypomanic (FM) or depressed (FD). They were compared on demographic and
      clinical variables. Logistic regression adjusting for potential confounds tested
      the association between first episode polarity and history of suicide attempt.
      RESULTS: Multiple logistic regression analysis showed that FD group membership
      was associated with eightfold odds of a past suicide attempt, adjusting for years
      ill and total number of lifetime major depressive episodes. LIMITATIONS: Sample
      size, retrospective design, recall bias, assessment during a mood episode, and
      imprecise recall of hypomania. CONCLUSIONS: Polarity of patients' first reported
      mood episode suggested a depression-prone subtype with a greater probability of
      past suicide attempt. The FM group had more alcoholism and psychosis, but less
      likelihood of past suicide attempt. Validation of these putative subtypes
      requires prospective study.

PMID- 17434599
TI  - Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar
      disorder.
AB  - BACKGROUND: The role of cytokines in bipolar disorder is still controversial.
      Although a few studies have found alterations of cytokines in bipolar disorder,
      their findings were inconsistent. The aim of this study was to determine whether
      the cytokines are involved in the pathophysiology of bipolar disorder. METHODS: A
      total of 37 manic patients with bipolar disorder and 74 control subjects were
      recruited. The mitogen-induced production of tumor necrosis factor (TNF)-alpha,
      interleukin-6 (IL-6), IL-4, interferon (IFN)-gamma, and IL-2 was measured using
      quantitative sandwich ELISA at the time of admission and 6 weeks after mood
      stabilizer treatment. RESULTS: IL-6 and TNF-alpha production of bipolar manic
      patients was significantly higher than those of normal controls, while IL-4
      values of the patients were significantly lower than normal controls. IL-6/IL-4,
      TNF-alpha/IL-4, IL-2/IL-4, and IFN-gamma/IL-4 ratios were significantly higher in
      bipolar manic patients than in normal controls. After 6 weeks of treatment, the
      levels of IL-6 significantly decreased compared with baseline. LIMITATIONS: The
      effect of various types of mood stabilizers on cytokine production should be
      considered. CONCLUSIONS: These findings suggest that the increased activity of
      pro-inflammatory cytokines and an imbalance between pro-inflammatory and anti
      inflammatory cytokines may play a role in the pathophysiology of bipolar
      disorder.

PMID- 17434600
TI  - Indications of anti-HY immunity in recurrent placental abruption.
AB  - PROBLEM: Placental abruption is a potential life-threatening condition for both
      the fetus and the mother, being significantly more common in pregnancies with
      male fetuses. The pathogenesis of placental abruption remains unknown. However,
      some recent reports point toward a maternal immune response against the fetus as
      a possible mechanism. No data exist concerning special characteristics of
      patients suffering recurrent placental abruptions. METHOD OF STUDY:
      Identification of all patients with recurrent placental abruption in a
      retrospective review of 881 consecutive Caucasian women seen in our tertiary
      centre for recurrent pregnancy losses between 1986 and 2005. The HLA, DRB1, DRB3,
      4, 5 and DQB1 genotypes of patients were compared with relevant controls.
      RESULTS: Eight patients were identified with recurrent placental abruption. The
      patients had a total of 22 abruptions; 18 (82%) in which the fetus died. Seven
      patients (88%) had first-born boys, and 15 abruptions (68%) involved male
      fetuses. All patients with a first-born boy, except one, had HLA-class II alleles
      known to restrict CD4+ T-cell responses against male-specific minor
      histocompatibility (HY)-antigens (HLA-DRB1*15, HLA-DRB3*0301 and HLA-DQB1*05).
      Haplotypes with these HLA-alleles constituted 64% of the patients' haplotypes
      compared to 28% of those of the controls (p=0.009). Furthermore, 43% of the
      patients were homozygous for these haplotypes compared to 5% of controls
      (p=0.023). CONCLUSION: We have found that recurrent placental abruption is
      exclusively almost preceded by the birth of a boy and the majority of patients
      have HLA-class II known to restrict CD4 T-cell reactions against HY-antigens.
      This indicates that maternal immunological responses against HY-antigens play a
      role in recurrent placental abruption.

PMID- 17434601
TI  - Taxonic structure of schizotypal personality in nonclinical subjects: Issues of
      replicability and age consistency.
AB  - To assess the replicability and age consistency of the taxonic structure and base
      rate of schizotypy, 803 university students (21.9 years) and 929 high school
      students (16.4 years) were administered three self-report measures of schizotypal
      personality. The two groups came from the same town and were matched on gender.
      MAXCOV analyses were consistent with a low base-rate taxon of approximately 10%
      only in the university student group; in the younger group, the three schizotypal
      personality measures did not show clear evidence of taxonicity. These findings
      support the hypothesis of the taxonic structure of schizotypal personality in
      adult subjects, but they raise questions concerning the identification of
      schizotypy in younger samples.

PMID- 17434603
TI  - A letter to the editor in reply to "susceptibility to guillain-barre syndrome is
      associated to polymorphisms of CD1 genes" by Caporale et al. in the J of
      Neuroimmunology (2006), 177:112-118.

PMID- 17434602
TI  - Plasma homovanillic acid levels in schizophrenic patients: correlation with
      negative symptoms.
AB  - The relation between changes in the levels of plasma homovanillic acid (pHVA) and
      clinical evolution during neuroleptic treatment of schizophrenic patients has not
      been satisfactorily characterized, as a number of conflicting findings have been
      reported. Significant correlations have generally been found using the assessment
      of positive symptoms as an index of clinical outcome. Nevertheless, attempts to
      correlate pHVA concentrations with negative symptoms have yielded contradictory
      results. With a view to evaluating if different responses in negative symptoms
      are associated with distinct pHVA profiles, we examined the levels of pHVA in 46
      neuroleptic-free schizophrenic patients and in these patients after neuroleptic
      treatment. Negative and positive symptoms were also addressed before and after
      treatment. Our results reveal that at least two classes of negative symptoms
      exist; the clinical evolution of the first class of negative symptoms parallels
      that of positive symptoms, and clinical improvement correlates with reduced
      dopaminergic activity. In contrast, in the second class, reduced dopaminergic
      activity is associated with a further deterioration of negative symptoms. These
      findings corroborate the heterogeneity of negative symptoms and may contribute to
      a better definition of endophenotypes in the schizophrenic syndrome.

PMID- 17434604
TI  - Effects of low-level formaldehyde exposure on synaptic plasticity-related gene
      expression in the hippocampus of immunized mice.
AB  - We examined the effects of inhalative exposure to formaldehyde (FA, 400 ppb) on N
      methyl-D-aspartate (NMDA) receptor subunits (NR2A and NR2B), dopamine receptor
      subtypes (D1 and D2), cyclic AMP responsive element-binding protein (CREB)-1,
      CREB-2, FosB/DeltaFosB, and transient receptor potential vanilloid receptor
      (TRPV1) in the hippocampus of ovalbumin-immunized mice using quantitative real
      time PCR. Western blot analyses for pCREB were performed. The mRNA levels of
      NR2A, D1 and D2 receptors, and CREB-1 were significantly increased by FA, but
      NR2B, CREB-2, FosB/DeltaFosB, and TRPV1 mRNA levels remained unchanged. Treatment
      with MK-801 normalized the mRNA levels induced by FA. There was no significant
      effect of FA exposure and MK-801 treatment on the protein level of pCREB. These
      results indicate that FA exposure selectively up-regulates hippocampal gene
      expression in immunologically sensitized mice. The FA effects are presumably
      mediated by glutamatergic neurotransmission through NMDA receptors.

PMID- 17434605
TI  - Partially double-stranded linear DNA probes: novel design for sensitive detection
      of genetically polymorphic targets.
AB  - Genetically polymorphic targets present a significant challenge to the
      reliability of detection and quantification by nucleic acid-based assays. A probe
      system with enhanced mismatch tolerance would be advantageous for such
      applications. The present study introduces a novel class of DNA probes,
      designated as partially double-stranded linear probes, composed of a long target
      specific strand 5' labeled with a fluorophore and a markedly shorter quencher
      strand, complementary to the 5' end of the target-specific strand, that is 3' end
      labeled with a quencher moiety. The utility of this probe system for sensitive
      detection of amplification products was demonstrated in a real-time PCR format.
      Comparison of multiple partially double-stranded linear probe combinations
      revealed that increased asymmetry in strand length was associated with improved
      mismatch tolerance. Notably, for a 45-mer/11-mer combination, the difference in
      threshold cycle values obtained for a perfectly matched target and one containing
      six mismatches was <1.5 cycles. The capacity for superior mismatch tolerance,
      ease of design, simplicity and flexibility of application are characteristics
      that make this new class of probes a desirable alternative for homogeneous
      detection of targets with a high level of genetic heterogeneity.

PMID- 17434606
TI  - Two chronic motor training paradigms differentially influence acute instrumental
      learning in spinally transected rats.
AB  - The effect of two chronic motor training paradigms on the ability of the lumbar
      spinal cord to perform an acute instrumental learning task was examined in
      neonatally (postnatal day 5; P5) spinal cord transected (i.e., spinal) rats. At
      approximately P30, rats began either unipedal hindlimb stand training (Stand-Tr;
      20-25min/day, 5days/week), or bipedal hindlimb step training (Step-Tr; 20min/day;
      5days/week) for 7 weeks. Non-trained spinal rats (Non-Tr) served as controls.
      After 7 weeks all groups were tested on the flexor-biased instrumental learning
      paradigm. We hypothesized that (1) Step-Tr rats would exhibit an increased
      capacity to learn the flexor-biased task relative to Non-Tr subjects, as
      locomotion involves repetitive training of the tibialis anterior (TA), the ankle
      flexor whose activation is important for successful instrumental learning, and
      (2) Stand-Tr rats would exhibit a deficit in acute motor learning, as unipedal
      training activates the ipsilateral ankle extensors, but not flexors. Results
      showed no differences in acute learning potential between Non-Tr and Step-Tr
      rats, while the Stand-Tr group showed a reduced capacity to learn the acute task.
      Further investigation of the Stand-Tr group showed that, while both the
      ipsilateral and contralateral hindlimbs were significantly impaired in their
      acute learning potential, the contralateral, untrained hindlimbs exhibited
      significantly greater learning deficits. These results suggest that different
      types of chronic peripheral input may have a significant impact on the ability to
      learn a novel motor task, and demonstrate the potential for experience-dependent
      plasticity in the spinal cord in the absence of supraspinal connectivity.

PMID- 17434607
TI  - Toxicity of the booster biocide Sea-Nine to the early developmental stages of the
      sea urchin Paracentrotus lividus.
AB  - The toxicity of the alternative antifouling compound Sea-Nine to the early
      developmental stages of the sea urchin Paracentrotus lividus was investigated.
      The inhibition of the fertilization rate and the induction of transmissible
      damages to the offspring, measured as inhibition of embryonic development and
      larval growth, were studied by preexposure of gametes to a range of Sea-Nine
      concentrations. Sperm and egg exposures resulted in a significant decrease of the
      fertilization rate and induced a transmissible damage to the offspring. The
      effects of Sea-Nine throughout the embryonic development were also studied by a
      48 h exposure of fertilized eggs. The larval growth was the most sensitive
      response tested, with toxic effects detected at 8.6 nM=2.4 microg/L (EC(10)). The
      inhibition of P. lividus embryonic development and larval growth was also used to
      study the loss of toxicity in Sea-Nine solutions exposed for 8h to direct
      sunlight and maintained for 28 h in dark conditions. The results showed that the
      toxicity of Sea-Nine solutions did not decrease but a slight increase in toxicity
      was observed in comparison with control solutions. The risk of Sea-Nine maximum
      concentrations measured in marinas around Europe to P. lividus early
      developmental stages was calculated and the obtained risk quotient was 5.5,
      indicating that adverse ecological effects of this compound are likely to occur.

PMID- 17434608
TI  - Glucagon-like peptide 1 (GLP-1) suppresses ghrelin levels in humans via increased
      insulin secretion.
AB  - INTRODUCTION: Ghrelin is an orexigenic peptide predominantly secreted by the
      stomach. Ghrelin plasma levels rise before meal ingestion and sharply decline
      afterwards, but the mechanisms controlling ghrelin secretion are largely unknown.
      Since meal ingestion also elicits the secretion of the incretin hormone glucagon
      like peptide 1 (GLP-1), we examined whether exogenous GLP-1 administration
      reduces ghrelin secretion in humans. PATIENTS AND METHODS: 14 healthy male
      volunteers were given intravenous infusions of GLP-1(1.2 pmol x kg(-1) min(-1))
      or placebo over 390 min. After 30 min, a solid test meal was served. Venous blood
      was drawn frequently for the determination of glucose, insulin, C-peptide, GLP-1
      and ghrelin. RESULTS: During the infusion of exogenous GLP-1 and placebo, GLP-1
      plasma concentrations reached steady-state levels of 139+/-15 pmol/l and 12+/-2
      pmol/l, respectively (p<0.0001). During placebo infusion, ghrelin levels were
      significantly reduced in the immediate postprandial period (p<0.001), and rose
      again afterwards. GLP-1 administration prevented the initial postprandial decline
      in ghrelin levels, possibly as a result of delayed gastric emptying, and
      significantly reduced ghrelin levels 150 and 360 min after meal ingestion
      (p<0.05). The patterns of ghrelin concentrations in the experiments with GLP-1
      and placebo administration were inversely related to the respective plasma levels
      of insulin and C-peptide. CONCLUSIONS: GLP-1 reduces the rise in ghrelin levels
      in the late postprandial period at supraphysiological plasma levels. Most likely,
      these effects are indirectly mediated through its insulinotropic action. The GLP
      1-induced suppression of ghrelin secretion might be involved in its anorexic
      effects.

PMID- 17434609
TI  - A novel rice C2H2-type zinc finger protein lacking DLN-box/EAR-motif plays a role
      in salt tolerance.
AB  - A cDNA for the gene ZFP182, encoding a C2H2-type zinc finger protein, was cloned
      from rice by RT-PCR. ZFP182 codes an 18.2 kDa protein with two C2H2-type zinc
      finger motifs, one nuclear localization signal and one Leu-rich domain. The DLN
      box/EAR-motif, which exists in most of plant C2H2-type zinc finger proteins, does
      not exist in ZFP182. The expression analysis showed that ZFP182 gene was
      constitutively expressed in leaves, culms, roots and spikes at the adult rice
      plants, and markedly induced in the seedlings by cold (4 degrees C), 150 mM NaCl
      and 0.1 mM ABA treatments. The approximate 1.4 kb promoter region of ZFP182 gene
      was fused into GUS reporter gene and transformed into tobacco. The histochemical
      analysis revealed that GUS expression could not be detected in transformed
      tobacco seedlings under normal conditions, but strongly observed in tobacco leaf
      discs and the vascular tissue of roots treated with NaCl or KCl. Expression of
      ZFP182 in transgenic tobacco and overexpression in rice increased plant tolerance
      to salt stress. These results demonstrated that ZFP182 might be involved in plant
      responses to salt stress.

PMID- 17434610
TI  - Isolated right ventricular dysfunction without myocardial infarction.
AB  - Right ventricular (RV) infarction or dysfunction is commonly complicated with
      acute inferior myocardial infarction. In this report, we describe a patient with
      unstable angina pectoris who showed a temporary isolated RV dysfunction. The
      patient had total occlusion of proximal right coronary artery, including RV
      branch, with good collateral circulation from left coronary artery.
      Recanalization was obtained by percutaneous coronary intervention (PCI).
      Echocardiography at admission showed RV dilatation and severe hypokinesis of RV
      free wall but no left ventricular wall motion abnormalities. Hemodynamic
      examination showed high right atrial pressure with a non-compliant pattern and
      low cardiac output immediately after PCI. Cardiac enzymes were not elevated even
      after PCI. RV asynergy and hemodynamics were improved at 2 days after PCI. The 99
      m technetium-pyrophosphate and 201 thallium dual single-photon emission computed
      tomography showed uptake of 99 m technetium-pyrophosphate in only the RV free
      wall, but in the left ventricle no uptake of 99 m technetium-pyrophosphate and no
      perfusion defect of 201 thallium.

PMID- 17434611
TI  - A patient with double right coronary artery and acute inferior myocardial
      infarction due to the critical lesion in one of them.

PMID- 17434612
TI  - How to image Kawasaki disease: a validation of different imaging techniques.
AB  - Kawasaki disease contributes to coronary artery aneurysm in 25% of patients.
      Cardiovascular imaging has an important role in diagnosis and follow-up of these
      cases. Echocardiography is the bedside technique of choice during the acute phase
      of the disease. MRI can be a valuable tool especially in adolescents, where
      sometimes echocardiography fails to detect coronary abnormalities and it has also
      the advantage of simultaneous perfusion, function and viability evaluation. If
      MRI is not available, a combination of echocardiography and SPECT gives an
      overview of anatomy, function and perfusion. MSCT is of limited value for follow
      up because of radiation and the misleading data due to coronary calcifications. X
      ray coronary angiography is kept mainly for cases where an invasive procedure
      should be performed.

PMID- 17434613
TI  - Cutting-balloon angioplasty effectively facilitates the interventional procedure
      and leads to a low rate of recurrent stenosis in ostial bifurcation coronary
      lesions: A subgroup analysis of the NICECUT multicenter registry.
AB  - BACKGROUND: Displacement of plaque is a major concern during coronary
      intervention of ostial bifurcation lesions. For this reason, angioplasty involves
      complex stenting procedures, which may trigger development of restenosis in a
      previously non-diseased parent vessel. OBJECTIVES: To examine, whether plaque
      displacement may be prevented by scoring atherosclerotic plaque with a cutting
      balloon (CB) stand-alone procedure. METHODS: Data of patients with Duke E and B
      type ostial bifurcation lesions (>/=70% stenosis involving a diagonal and/or
      marginal branch >2 mm deriving from a non-diseased parent vessel), who were
      treated with CB as stand-alone procedure within the prospective NICECUT
      multicenter trial were analyzed. Primary endpoint was the rate of binary stenosis
      and target lesion revascularization (TLR). Secondary endpoints were procedural
      success and major adverse cardiac events (MACE) at 6-months follow-up. RESULTS:
      63 out of 65 lesions (56 patients) were successfully amenable to treatment with
      CB (96.4% procedural success). 76.9% of patients were successfully treated with
      CB as a stand-alone procedure, while provisional stenting was necessary in 23.1%.
      At follow-up, binary stenosis was found in 23.2%, among the total population.
      Total rate of TLR and MACE were 7.7% and 3.6%, respectively, compared to 4.0% and
      2.0% in patients for whom CB stand-alone procedure was feasible, while it was
      20.0% and 6.7% for stented lesions. CONCLUSIONS: CB angioplasty as a stand-alone
      procedure may facilitate interventional treatment of ostial bifurcation lesions
      and may help to avoid complex stenting procedures. It is associated with a low
      rate of binary stenosis and TLR.

PMID- 17434614
TI  - Steepened aortoseptal angle may be a risk factor for discrete subaortic stenosis
      in adults.
AB  - Discussion exists whether discrete subaortic stenosis (DSS) is a congenital or
      acquired cardiac defect. Currently, it is regarded an "acquired" cardiac defect
      presumably secondary to altered flow patterns due to morphological abnormalities
      in the left ventricular outflow tract, as have been shown by some studies in the
      pediatric population. In this report, we demonstrated a steepened aortoseptal
      angle in adults with DSS without previous cardiac surgery in comparison to
      controls. Our results strengthen the hypothesis that altered flow patterns due to
      a steepened aortoseptal angle are a substrate for development of DSS in adults.

PMID- 17434615
TI  - Complete angiographic resolution of spontaneous coronary artery dissection
      associated with sleep deprivation.
AB  - We describe a case of complete angiographic resolution of spontaneous coronary
      artery dissection associated sleep deprivation with a successful medical
      management. A 40-year-old woman presented to our emergency department with
      squeezing chest pain following 72 h sleep deprivation. Coronary angiography
      demonstrated longitudinal dissection of the middle part of the diagonal artery
      with TIMI III flow to the distal part of the vessel. The dissected vessel was
      small to intervene so we decided to treat it conservatively with antiplatelet
      agents and heparin. She remained free of chest pain during the hospitalization
      period and was discharged in good condition. We continued to treat her in the
      outpatient clinic with antiplatelet agents and the patient no longer complained
      of chest pain. At six months, coronary angiography demonstrated complete
      resolution of the previously dissected coronary artery.

PMID- 17434616
TI  - The incidence and clinical impact of stent strut fractures developed after drug
      eluting stent implantation.
AB  - BACKGROUND: Cases of stent strut fractures (SSFs) after DES implantation have
      been reported, but the clinical significance is uncertain. Then we sought to
      define the incidence and clinical implications of SSFs developed after drug
      eluting stent (DES) implantation. METHODS: We gathered SSF cases from 13 centers
      in Korea retrospectively. SSF was defined as angiographically visible interrupted
      connection of stent struts or fewer visible stent struts at the suspected site
      than normally looking stented area on intravascular ultrasound (IVUS).
      Furthermore, we classified the SSFs cases into three patterns (disruption,
      avulsion, and displacement) according to the interruption site and absence or
      presence of displacement. RESULTS: Thirty-seven SSFs (2 disruption, 7 avulsion,
      28 displacement) were detected in 35 lesions in 35 patients. All fractured stents
      were sirolimus-eluting stents (SESs). The incidence of SSFs was 0.84% and the
      proportion of restenosis related with SSF was 6.3% after SES implantation driven
      from the data of 8 centers. The average length of stent used was 49 mm,
      overlapping stenting was performed in 19 lesions (54%), and the average maximal
      angulation in the initial coronary angiography was 67 degrees . Twenty-four
      fractures (65%) were associated with focal in stent restenosis and 11 fractures
      (30%) with target lesion revascularization. No acute coronary syndrome developed.
      CONCLUSIONS: SSF after DES implantation might be a considerable complication
      after DES implantation especially after SES implantation.

PMID- 17434618
TI  - HMG-CoA reductase inhibition improves anti-aging klotho protein expression and
      arteriosclerosis in rats with chronic inhibition of nitric oxide synthesis.
AB  - BACKGROUND: The klotho gene and its protein product are mainly expressed in the
      kidney. The klotho protein induces suppression of multiple aging-related
      phenotypes, and homozygous klotho gene mutant mice display various senescent
      morbidity. Chronic inhibition of nitric oxide synthase (NOS) induces
      arteriosclerosis, while HMG-CoA reductase inhibitors (statins) have pleiotropic
      vascular protective effects besides cholesterol lowering. Therefore, the present
      studies were performed to determine whether chronic NOS blockade would affect
      anti-ageing klotho protein expression. In addition, the effects of statins on
      klotho protein expression and arteriosclerosis in these rats were investigated.
      METHODS: Forty-two rats were divided into 6 groups as follows: (1) control, (2)
      NOS blockade, (3) atorvastatin (10 mg/kg/day), (4) pitavastatin (3 mg/kg/day),
      (5) NOS blockade+atorvastatin, (6) NOS blockade+pitavastatin. To induce
      arteriosclerosis further, a cuff was placed around the left femoral artery in
      each rat. After 4 weeks observation, rats were killed and renal klotho expression
      and the level of arteriosclerosis were examined. RESULTS: The rats of chronic NOS
      inhibition developed hypertension, while statin treatment did not affect blood
      pressure in the rats with or without NOS blockade. Despite statin treatment,
      plasma levels of lipids did not differ among 6 groups. Immunohistochemical
      staining revealed that klotho protein was localized in the renal tubules. Chronic
      NOS inhibition markedly reduced renal klotho protein expression, while treatment
      with atorvastatin or pitavastatin completely prevented the reduction of klotho
      expression induced by NOS inhibition. In addition, statin treatment significantly
      improved arteriosclerotic lesions induced by NOS inhibition and cuff placement.
      CONCLUSION: Since statin treatment did not alter blood pressure or serum lipid
      profiles, a novel vascular protective effect of statins via enhancing anti-aging
      klotho protein expression is suggested.

PMID- 17434619
TI  - A brief office intervention is associated with increased days per week of
      exercise.
AB  - OBJECTIVE: We hypothesized that a cardiologist-initiated motivational discussion
      during a routine general cardiology clinic visit that included an exercise
      'contract' signed by the patient, physician and a witness, would increase self
      reported days per week of exercise. METHODS: A short-term pilot intervention was
      provided to forty consecutive general cardiology clinic patients who were
      enrolled in 2005. They were asked to answer the question "How many days each week
      do you exercise" prior to the motivational discussion and at routine follow-up.
      Each participant signed an exercise 'contract' and agreed to exercise for at
      least 15 min everyday. RESULTS: Participants had an average follow-up of 3.2
      (1.7) months. The initial visit mean days of exercise per week were 3.1 (1.9). At
      follow-up, mean days of exercise per week were 4.0 (1.8), (p=0.04). CONCLUSION:
      This simple rapid intervention was associated with increased self-reported days
      per week of exercise.

PMID- 17434617
TI  - Safety and efficacy of the CYPHER Select Sirolimus-eluting stent in the "Real
      World"--clinical and angiographic results from the China CYPHER Select registry.
AB  - OBJECTIVE: This post-marketing surveillance registry is aimed at determining the
      safety and reliability of the CYPHER Select Sirolimus-eluting stent (SES) in
      routine clinical practice. BACKGROUND: Little information and angiographic follow
      up data in large-scale "real world" registry is available for the CYPHER Select
      SES, an advanced-generation SES. METHODS: This was a prospective multicenter (20
      centers) registry. 1189 consecutive patients who received at least 1 CYPHER
      Select SES during daily clinical practice were enrolled. Patients who underwent
      emergency stenting for acute myocardial infarction were excluded. RESULTS: The
      procedure's success rate was 98.3% for CYPHER Select SES implantation, and follow
      up rates were 98% with 100% data auditing. Target lesion revascularization (TLR)
      at 12 months occurred in 60 (5.14%) cases, cardiac death in 13 cases (1.11%), Q
      wave myocardial infarction (MI) in 5 cases (0.43%), non-Q-MI in 9 cases (0.77%),
      target vessel revascularization (TVR) in 67 cases (5.74%), and MACE defined as
      cardiac death, nonfatal MI and TLR in 76 cases (6.51%). MACE-free survival rate
      at 12 months was 93.7%. Angiographic follow-up at 9 months was performed in 418
      (68.3%) lesions treated by CYPHER Select SES. The binary restenosis rate was 4.8%
      in-stent and 9.6% in-segment. Subgroup analysis showed diabetes, bifurcation
      lesion and combined use of different stents were independent risk factors of
      cumulative MACE. In-segment MLD </=2.25 mm at post-procedure and ostial lesion
      was independent predictors of in-segment restenosis. CONCLUSIONS: In this
      registry, the MACE, TLR, angiographic late loss and binary restenosis rates of
      CYPHER Select SES were similar to those reported in SES randomized trials and
      "real world" registries. The safety and efficacy of CYPHER Select SES shown in
      this registry are consistent with those seen in SES studies.

PMID- 17434620
TI  - Midventricular peak systolic strain and Tei index of the right ventricle
      correlated with decreased right ventricular systolic function in patients with
      acute pulmonary thromboembolism.
AB  - BACKGROUND: Assessment of right ventricular (RV) systolic function remains
      difficult because of the RV's complex shape. We aimed to evaluate RV systolic
      function with strain analysis in patients with acute pulmonary thromboembolism
      (PTE). PATIENTS AND METHODS: From March 2005 to June 2006, 28 consecutive
      patients with acute PTE were included in this study. After excluding four
      patients, three with recurrent episodes of PTE and one with permanent pacemaker,
      the remaining 24 patients (10 males, mean age 69.0+/-10 years) were analyzed.
      RESULTS: Mean RV fractional area change (RVFAC) was 20.1+/-8.7%; RV Tei index was
      0.86+/-0.23; tricuspid annular plane systolic excursion (TAPSE) was 1.56+/-0.31
      cm; and TR Vmax was 3.6+/-0.4 m/s at the time of diagnosis. Midventricular peak
      systolic strain of RV was markedly decreased (base: -18.0+/-6.6%, midventricle: 
      5.4+/-12.8%, apex: -10.6+/-8.1%). After treatment, follow-up echocardiographic
      data were obtained from 20 patients (mean: 11.0+/-8.2 days, duration: 4-34 days).
      Mean RVFAC, RV Tei index, TAPSE and TR Vmax were significantly improved
      (P<0.001). Midventricular peak systolic strains of RV were also significantly
      improved (base: -20.9+/-7.0%, P=0.055, midventricle: -21.1+/-6.8%, P<0.001, apex:
      -12.7+/-8.1%, P=0.314). Midventricular peak systolic strain of RV showed
      significant negative correlation with RVFAC (r=-0.660, P<0.001) and TAPSE (r=
      0.642, P<0.001). Also, the RV Tei index showed significant correlation with RVFAC
      (r=-0.646, P<0.001) and TAPSE (r=-0.647, P<0.001). CONCLUSIONS: Midventricular
      peak systolic strain and RV Tei index decreased in the patients with acute PTE
      and improved after stabilization. These values can therefore be used to assess RV
      systolic function in patients with acute PTE.

PMID- 17434621
TI  - Antithrombotic treatment for patients on oral anticoagulation undergoing coronary
      stenting: a review of the available evidence and practical suggestions for the
      clinician.
AB  - BACKGROUND: Dual antiplatelet treatment with aspirin and a thienopyridine is the
      antithrombotic treatment recommended after coronary stenting. Such strategy is
      generally not applicable in most patients with an indication for oral
      anticoagulation (OAC), for whom however, information about the optimal
      antithrombotic regimen is currently limited. METHODS: In order to derive some
      practical indications for the clinicians who are requested to care for these
      patients, the available evidence on the use, safety and efficacy of the various
      antithrombotic strategies was reviewed. RESULTS: A substantial variability in the
      choice of treatment was observed in current practice where, however, standardized
      management protocols are seldom used. Triple therapy with OAC, aspirin and a
      thienopyridine is the most frequently adopted regimen, although its safety
      appears suboptimal, due to an apparent increased incidence of major hemorrhagic
      complications. Conversely, the efficacy of the combination of OAC and aspirin is
      suboptimal, so that such regimen should be considered only for patients at very
      high hemorrhagic risk, and in association with the implantation of more
      "biocompatible" stents. CONCLUSIONS: While waiting for further studies to
      generate more consistent evidence, the choice of the antithrombotic treatment for
      patients with an indication for OAC undergoing coronary stenting should be guided
      by careful stratification of both thrombotic/thromboembolic and hemorrhagic
      risks. In general, however, the implantation of drug-eluting stents should be
      avoided, due to the prolonged need for dual antiplatelet administration, and the
      radial approach preferred, due to the virtual elimination of bleeding
      complications at the arterial access site.

PMID- 17434622
TI  - A subacute bacterial endocarditis in a patient with aortic prosthetic valve due
      to Listeria monocytogenes presenting with perivalvular leak.

PMID- 17434623
TI  - Successful percutaneous coronary angioplasty in a patient with anomalous origin
      of the right coronary artery from the left anterior descending artery.

PMID- 17434624
TI  - Effects of garlic on defibrillation efficacy.

PMID- 17434625
TI  - Congenital heart disease manifested as acute abdominal pain.
AB  - We present a case of a 53-year-old man with complaints of severe abdominal pain
      and nausea. Emergency department abdominal workup was non-diagnostic. Physical
      examination revealed signs of right- and left-heart failure. A past medical
      history of dysrhythmias and chronic abdominal complaints prompted hospital
      admission. Subsequent right heart catheterization revealed a significant left-to
      right shunt. CT scan of the chest and angiography confirmed the diagnosis of an
      abnormal ascending vein between the innominate vein and the left superior
      pulmonary vein. After the anomalous vein was ligated, the patient's abdominal
      pain resolved.

PMID- 17434626
TI  - The longest documented left main coronary artery.
AB  - The left main coronary angiography (LMCA) ranges from 3 to 6 mm in diameter and
      may be up to 10 to 15 mm in length in humans. We here report a case of the
      longest LMCA (38 mm) in a 60-year-old woman with subacute anterior myocardial
      infarction. In coronary angiography and coronary computerized tomography LMCA was
      measured to be 38 mm long.

PMID- 17434627
TI  - Diagnostic dilemma in a middle-aged man with heart failure.
AB  - We report a middle-age man presented with shortness of breath. Echocardiography
      revealed globally hypokinetic LV with poor function. Coronary angiograms showed
      no obstructive coronary artery lesions but multiple coronary fistulae to
      pulmonary artery without significant left to right shunt. Cardiac magnetic
      resonance imaging demonstrated normal myocardial perfusion and absence of
      myocardial scarring. His condition improved with medications with fistulae left
      untreated. This case illustrates the importance of functional assessment of a
      rare clinical condition (coronary fistula) in patients with common clinical
      presentation (congestive heart failure) prior to definitive treatment.

PMID- 17434628
TI  - Prosthetic heart valves: types and echocardiographic evaluation.
AB  - In the last five decades multiple different models of prosthetic valves have been
      developed. The purpose of this article is to provide a comprehensive source of
      information for the types and the echocardiographic evaluation of the prosthetic
      heart valves.

PMID- 17434629
TI  - Mechanisms responsible for the initiation and maintenance of atrial fibrillation
      assessed by non-contact mapping system.
AB  - BACKGROUND: This study is aimed to assess the initiation and maintenance
      mechanisms of atrial fibrillation (AF) and their relationships with the
      anatomical structures of the left atrium (LA) and pulmonary veins (PVs). METHODS:
      Thirty-seven patients (pts; 33 men, mean age 50+/-12, range 25-68 years) with
      paroxysmal AF (n=29) and persistent AF (n=8) who underwent mapping of the LA and
      PV using 3D non-contact endocardial mapping system (EnSite 3000) were included.
      Atrial premature complexes (APCs) which triggered the initiation of AF lasted
      longer than 1 min were mapped and the activation sequence on isopotential color
      maps was analyzed. RESULTS: Wave front dynamics and the relationship with the
      underlying anatomical structures were assessed. APCs from PV were related to the
      initiation of AF, but not to the maintenance of AF in 59.5% of the pts (focally
      triggered type) whereas APCs from PV not only initiated AF but also maintained AF
      without continuous triggering in 27% (focally driven type). Mixed type and
      indeterminate type of AF was in 4.5% and 13.5%, respectively. During AF, the mean
      number of wavelet was 1.45 (maximum 3 in 76.5%). Anatomical structures showing
      frequent wave break and slow conduction were mostly located at the septopulmonary
      bundle (86.5%) and the posterior LA roof between left superior PV and right
      superior PV (54.1%). CONCLUSION: Focal repetitive activity from PV played an
      important role in both initiation and maintenance of AF using NCM study. Specific
      anatomical structures such as septopulmonary bundle or posterior LA roof were
      associated with the spontaneous wave break and heterogeneous conduction delay,
      which was also appears to be important in the maintenance of AF.

PMID- 17434630
TI  - Assessment of P-wave duration and dispersion in patients with isolated coronary
      artery ectasia.
AB  - INTRODUCTION: Coronary artery ectasia (CAE) is defined as localized or diffuse
      dilatation of the epicardial coronary arteries. We sought to determine whether
      isolated CAE may alter P-wave duration and dispersion (PD). METHODS: The study
      population consisted of 26 patients (mean age: 61.6+/-11.0 years) with isolated
      CAE (group 1) and sex- and age-matched 26 control subjects (group 2). Both groups
      underwent a standard 12-lead surface electrocardiogram recorded at 50 mm/s.
      Maximal (P(max)) and minimal P-wave durations (P(min)) are measured. PD was
      defined as the difference between P(max) and P(min). RESULTS: In group 1, P(max)
      (114.2+/-10.4 ms vs 104.8+/-10.6 ms, p<0.002) and PD (34.0+/-12.7 ms vs 24+/
      10.6, p<0.004) were significantly higher than those of group 2. Moreover a
      significant correlation was found between P(max) and PD with ectatic segment
      number (r=0.625, r=0.626, respectively; p=<0.001); and P(max) and PD with ectatic
      vessel number (r=0.698, r=0.704 respectively; p=<0.0001). CONCLUSION: Isolated
      CAE and the degree of the ectasia were found to be associated with prolonged
      P(max) and PD.

PMID- 17434631
TI  - Impact of subclinical thyroid disorders on coronary heart disease, cardiovascular
      and all-cause mortality: a meta-analysis.
AB  - BACKGROUND: Previous studies have suggested that sub-clinical thyroid states may
      have detrimental effects on the coronary heart disease (CHD). Whether subclinical
      thyroid dysfunction is a risk factor for the above is controversial. METHODS: A
      systemic search of the literature using Pubmed, Medline and Ovid online tool was
      performed to identify relevant studies. Amongst the clinical studies,
      crossectional study and studies with follow-up period ranging between 4 and 20 yr
      were identified (Walsh JP, Bremner AP, Bulsara MK, et al. Subclinical thyroid
      dysfunction as a risk factor for cardiovascular disease. Arch Intern Med 2005 Nov
      28;165 (21):2467-72.; Rodondi N, Newman AB, Vittinghoff E, et al. Subclinical
      hypothyroidism and the risk of heart failure, other cardiovascular events, and
      death. Arch Intern Med 2005 Nov 28; 165 (21):2460-6.; Rotterdam study, Imaizumi
      M, Akahoshi M, Ichimaru S, et al. Risk for coronary heart disease and all-cause
      mortality in subclinical hypothyroidism. J Clin Endocrinol Metab 2004 Jul; 89
      (7):3365-70.; Capolla et al.; Parle JV, Maisonneuve P, Sheppard MC, Boyle P,
      Franklyn JA. Prediction of all-cause and cardiovascular mortality in elderly
      people from one low serum thyrotropin result: a 10-year cohort study. Lancet 2001
      Sep 15; 358 (9285):861-5). RESULTS: Sub-clinical hypothyroidism: The pooled
      estimate of the relative risk of CHD revealed significant difference both at
      baseline [RR with 95% CI: 1.533 (1.312-1.791), P<0.05] and at follow-up [RR with
      95% CI: 1.188 (1.024-1.379), P<0.05]. The relative risk of all-cause mortality at
      follow-up revealed no significant difference. However, the relative risk of death
      from cardiovascular causes at follow-up was significantly higher [RR with 95% CI:
      1.278 (1.023-1.597), P<0.05]. Sub-clinical hyperthyroidism: The pooled estimate
      of the relative risk of CHD revealed no significant difference both at baseline
      [RR with 95% CI: 1.156 (0.709-1.883)] and at follow-up [RR with 95% CI: 1.207
      (0.780-1.870)].The relative risk of death from cardiovascular causes at follow-up
      was also not significantly higher. CONCLUSION: The present meta-analysis
      indicates that sub-clinical hypothyroidism is associated with both, a significant
      risk of CHD at baseline and at follow-up. In addition, mortality from
      cardiovascular causes is significantly higher at follow-up. Sub-clinical
      hyperthyroidism is not associated with CHD or mortality from cardiovascular
      causes.

PMID- 17434632
TI  - Tako-tsubo-like left ventricular dysfunction in a patient with chronic total
      occlusion of the left anterior descending artery.
AB  - This report describes a case of tako-tsubo-like left ventricular dysfunction in a
      patient with chronically occluded left anterior descending artery. A 74-year-od
      female, experiencing severe pain due to osteoarthritis, presented with chest pain
      lasting for 6 h. Electrocardiography revealed ST-segment elevation in the
      anterior and lateral walls. Left ventriculography in the acute phase displayed an
      akinetic apex and hyperkinetic basal region. Emergent coronary angiography
      revealed total occlusion of the left anterior descending artery. Although direct
      coronary angioplasty to the totally occluded left anterior descending artery was
      unsuccessful, the left ventricular function returned to normal within three weeks
      after admission. Thallium scintigraphy showed no significant abnormality, and
      cardiac enzyme elevation showed only a slight increase. In this case, tako-tsubo
      like left ventricular dysfunction was considered to occur in the presence of
      chronically occluded left anterior descending artery.

PMID- 17434633
TI  - Rapid successful treatment for massive pulmonary thromboembolism by intravenous
      thrombolysis: depiction at multislice computed tomography.

PMID- 17434634
TI  - Association between serum resistin and carotid intima media thickness in
      hypertension patients.
AB  - BACKGROUND: Resistin is an adipocytokine belonging to the family of cysteine rich
      secretory proteins. We sought to determine if a correlation between resistin
      levels and carotid atherosclerosis exists in hypertensive patients. METHODS: This
      study consisted of 307 treated hypertensive patients. Subjects were grouped into
      tertiles according to their resistin level. RESULTS: Carotid intima media
      thickness (IMT) was significantly highest in the third tertile. The first tertile
      had a mean carotid IMT and a mean of maximum carotid IMT of 0.63+/-0.08 and
      0.81+/-0.10 mm, respectively. The 2nd tertile had measurements of 0.63+/-0.08 and
      0.81+/-0.12 mm, and the 3rd tertile 0.67+/-0.12 and 0.86+/-0.11 for the same
      parameters. (p=0.002). Resistin levels were independently associated with the
      carotid IMT (mean carotid IMT: R(2)=0.159, p<0.001 and mean of maximum carotid
      IMT: R(2)=0.162, p<0.001) after controlling for age, gender, HDL cholesterol,
      triglyceride, LDL cholesterol, smoking and DM. The tertile level of resistin was
      significantly associated with (odds ratio=3.097, p=0.004) risk of coronary artery
      disease after controlling for age, gender, HDL cholesterol, triglyceride, LDL
      cholesterol, smoking, DM and carotid IMT. CONCLUSION: Serum resistin is
      independently associated with increasing carotid IMT in treated hypertensive
      patients.

PMID- 17434635
TI  - Intravenous and oral administration of amiodarone for the treatment of recent
      onset atrial fibrillation after digoxin administration.
AB  - BACKGROUND: Atrial fibrillation (AF) remains a significant contributor to
      cardiovascular morbidity. Amiodarone is a potent antiarrhythmic drug. The safety
      and efficacy of oral versus intravenous (i.v.) Amiodarone in the treatment of AF
      of recent onset (duration <48 h) was investigated. METHODS: The study population
      consisted of 223 patients with symptomatic AF, of whom 110 received 600 mg oral
      Amiodarone (Group A) in three divided doses and 113 received i.v. Amiodarone (5
      mg/kg over 30 min followed by 1000 mg over the next 24 h) (Group B). Digoxin was
      administered to all patients, who had not previously received it. All patients
      were monitored for 24 h. RESULTS: Conversion to sinus rhythm occurred in 85.45%
      of group A and 82.30% in group B (p=NS). Mean time of cardioversion in group A
      was 20+/-4.5 h and in group B was 12+/-8 h (p<0,001). However, blood pressure
      (BP) in group A remained stable for the observation period, whereas it fell
      significantly in group B. Treatment was not discontinued in any of the patients
      in either group, however 13 patients in group B developed superficial phlebitis.
      CONCLUSIONS: Both forms of the drug are extremely efficient in restoring sinus
      rhythm in AF of recent onset, although the i.v. form acts quicker. The oral form
      of the drug does not alter significantly the patients' BP.

PMID- 17434636
TI  - Interactions between the chemical senses: trigeminal function in patients with
      olfactory loss.
AB  - The intranasal trigeminal and the olfactory system are intimately connected.
      There is evidence showing that acquired olfactory loss leads to reduced
      trigeminal sensitivity due to the lack of a central-nervous interaction. Both,
      the orbitofrontal cortex and the rostral insula appear to be of significance in
      the amplification of trigeminal input which is missing in patients with olfactory
      loss. On peripheral levels, however, adaptive mechanisms seem to produce an
      increase in the trigeminal responsiveness of patients with hyposmia or anosmia.

PMID- 17434637
TI  - L-argininamide improves the refolding more effectively than L-arginine.
AB  - L-arginine (Arg) is a widely used additive for suppressing protein aggregation
      during refolding. Systematic screening of Arg analogs provides superior additives
      that enhance the refolding yield more effectively than Arg. The refolding yield
      of hen egg lysozyme in the presence of 500 mM L-argininamide (ArgAd) increases
      1.7-fold higher than Arg. Thermal unfolding experiments indicate that ArgAd has a
      greater denaturing effect than Arg. The refolding yield positively relates to the
      net charge of Arg analogs. Moreover ArgAd was also effective for the refolding of
      bovine carbonic anhydrase. High potency to increase the refolding yield of ArgAd
      compared to Arg results from high positive net charge and the denaturing
      property.

PMID- 17434638
TI  - Engineering cartilage tissues with the shape of human nasal alar by using
      chondrocyte macroaggregate--Experiment study in rabbit model.
AB  - Despite of progresses in tissue engineering based on cell/scaffold strategy,
      uneven cell distribution as well as tissue formation in the scaffold, limited
      cell seeding efficiency and inflammatory reaction triggered by the degradation of
      scaffold remain problems to be resolved. In this study, we proposed a novel cell
      macroaggregate cultivation system, and explored a feasible strategy to construct
      three-dimensional cartilage tissue with shape of human nasal alar by using cell
      macroaggregate. Isolated chondrocytes was cultured at high density to form a
      monolayer chondrocyte sheet as well as expanded for seeding on the sheet to
      produce mechanically operable cell macroaggregate. Chondrocyte macroaggregates
      were then fabricated into transplants with shape of nasal alar by using Internal
      support or External scaffold techniques; results of in vivo chondrogenesis were
      investigated in immunocompetent animal. Chondrocyte macroaggregates presented
      long survival time and good viability; constructs fabricated using both
      techniques can develop into tissues with characteristic structure of native
      cartilage, glycosaminoglycans as well as type II collagen were highly produced in
      the ECM of engineered cartilages. By placing hyaluronan ester film as Internal
      support, the predetermined shape of the chondrocyte macroaggregate can be well
      maintained. In contrast, due to the poor mechanical stability of grafts
      fabricated in External scaffold group, obvious deformation occurred in harvested
      specimens. The experiment proved the usefulness of chondrocyte macroaggregate in
      cartilage regeneration, and provided a new strategy to engineer cartilage with
      special shape by using cell macroaggregate/biodegradable support.

PMID- 17434639
TI  - Analysis of codon usage bias and base compositional constraints in iridovirus
      genomes.
AB  - The codon usage bias and the base composition variations in the available 12
      complete iridovirus genome sequences have been investigated. We re-evaluated the
      number of open reading frames (ORFs) in each published iridovirus genome and
      analyzed its correlation against the genome size. The result shows that there is
      a direct relationship between the number of ORFs and the genome size. The codon
      usage patterns of these iridoviruses are found to be phylogenetically conserved.
      A significant variation in the base content among the 12 iridovirus genomes has
      been observed, with G+C content ranges widely from 27 to 55%. Moreover, the
      preferential use of bases in codons is different among higher and lower G+C
      content genomes. A preferential codon usage among viral genomes is also noticed.
      Effective number of codon (Enc) plot reveals that the G+C compositional
      constraint is the main factor that determines the codon usage bias. Relative
      synonymous codon usage analysis of methyltransferase containing as well as
      lacking viruses suggests that the codon usage is not influenced by the
      methylation-mediated mutation. In addition, the comparison of the codon usage of
      iridovirus hosts and the iridovirus genomes reveals that the host tRNA pool may
      be responsible for the base compositional constraint. This study represents the
      most comprehensive analysis to date for iridovirus codon usage patterns.

PMID- 17434640
TI  - Monitoring of dissolution induced changes in film coat composition by 1H NMR
      spectroscopy and SEM.
AB  - In our study we investigated the release mechanisms of coated oral dosage forms
      more deeply. The aim of the study was to monitor the buffer induced leaching out
      of water soluble compounds from Kollicoat SR films and to relate this process to
      the film properties and the release kinetics. Propranolol HCl tablets were coated
      with different amounts and ratios of polyvinyl acetate (Kollicoat SR) and
      poly(vinyl alcohol)-poly(ethylene glycol)-graft-copolymer (Kollicoat IR).
      Polyvinyl pyrrolidone (Kollidon 30) was added as a second water soluble polymer
      and triacetin as a plasticizer. In addition to kinetics of the drug release, the
      films were studied by SEM and 1H NMR spectroscopy. SEM micrographs revealed
      morphological changes of the tablet surface that were related to an alteration in
      film coat composition. The described 1H NMR method provided the opportunity to
      quantify the leaching of Kollicoat IR, Kollidon 30 and triacetin. Drug release
      kinetics were related to dissolution induced changes in coating composition.
      Permeability of the film coat increased, when about 90% of the water soluble
      polymers and plasticizer triacetin were leached out of the film coat.

PMID- 17434641
TI  - [Hoffmann syndrome presenting to the emergency department].
AB  - We report a case of hypothyroid myopathy, or Hoffmann syndrome, in a 31-year-old
      man who presented to the emergency department with asthenia, muscular pain,
      cramps, and joint pain. Tests revealed increased creatine phosphokinase level
      (8102 U/L) and severe hypothyroidism (content of T4=3.8 pg/ml, T3=1.3 pg/ml, and
      thyrotropin stimulating hormone>150 microU/ml). Other causes of myopathy were
      excluded by anamnestic investigation and paraclinical exam. Treatment was begun
      with thyroid hormones (from 75 to 175 microg) and good clinical evolution was
      rapid. The pathophysiology of hypothyroid myopathy, clinical aspects and
      pathologic anatomic elements are described. The exact etiology of hypothyroidism
      must be known because some pathologic features are benign and treatment can have
      good results, whereas others, such as cancer, have worse prognosis.

PMID- 17434642
TI  - [Complications in the elongation period during osseus lengthening.
      Characteristics of management in reeducation].

PMID- 17434643
TI  - Mutual information-based registration of temporal and stereo retinal images using
      constrained optimization.
AB  - In the registration of temporal and stereo retinal images, the rotation angle is
      normally less than 5 degrees and the scaling factor is between 0.95 and 1.05. Due
      to sitting constraints in the imaging process, the x translation can be more than
      100 pixels, but the y translation is usually small. This paper successfully
      incorporates these constraints in the mutual information-based registration and
      exploits a constrained optimization to seek an optimal registration. The proposed
      approach increases the success rate of the registration algorithm significantly.
      The impacts of the dynamic ranges of registration parameters on the registration
      outcome are studied and the effects of the order of rotation, scaling, and
      translation are also investigated.

PMID- 17434644
TI  - Gene manipulation through the use of small interfering RNA (siRNA): from in vitro
      to in vivo applications.
AB  - The conventional approach to investigate genotype-phenotype relationships has
      been the generation of gene targeted murine strains. However, the emergence of
      RNAi technologies has opened the possibility of much more rapid (and indeed more
      cost effective) genetic manipulation in vivo at the level of the transcriptome.
      Successful application of RNAi in vivo depends on intracellular targeted delivery
      of siRNA/shRNA molecules for efficient knockdown of the desired gene. In this
      review, we discuss the rationale and different strategies of using siRNA/shRNA
      for accomplishing the silencing of targeted genes in a spatial and /or temporally
      regulated manner. We also summarise the steps involved in extending these
      approaches to in vivo applications, with a specific focus upon the development of
      silencing in the mouse.

PMID- 17434645
TI  - Subcellular compartmentalisation of cadmium in white lupins determined by energy
      dispersive X-ray microanalysis.
AB  - The microlocalisation of cadmium (Cd) at the tissue-cellular level in Lupinus
      albus L. cv. Multolupa was determined by energy-dispersive X-ray microanalysis
      (EDXMA). Experimental plants were grown on Cd-treated (0 and 150 microM) perlite
      for 35 days. In leaves, Cd was found inside cells (cytoplasm or vacuoles),
      especially in the vascular bundle cells. Cd-induced damage of the chloroplast
      structure was also detected. EDXMA of the roots showed the cell wall to be the
      main area of Cd binding at the cellular level; only a small amount of Cd was
      found in the vacuoles. At the tissue level, a decreasing Cd gradient was seen
      from the outer to the inner root cortical parenchyma. Cd and S were found co
      localised in the vascular cylinder.

PMID- 17434646
TI  - Photodynamic therapy for cutaneous verrucous carcinoma.
AB  - Cutaneous verrucous carcinoma is a low-grade and well-differentiated variant of
      squamous cell carcinoma. This rare neoplasm follows a seemingly indolent
      progression and exhibits a low metastatic potential. Photodynamic therapy relies
      on the selective intratumoral cell accumulation and photoactivation of a
      photosensitizer, leading to the generation of phototoxic compounds responsible
      for necrosis and apoptosis of the target cells. An 82-year-old man presenting
      with a large long-standing verrucous carcinoma on the leg was treated
      successfully by 6 photodynamic therapy sessions administered at weekly intervals
      using methyl-aminolevulinate and 57-J/cm(2) irradiations at 634-nm wavelength.
      The use of methyl-aminolevulinate-photodynamic therapy for treating cutaneous
      verrucous carcinoma had not been reported so far. It may represent a convenient
      therapeutic alternative in this setting.

PMID- 17434647
TI  - Food-related sensory experience from birth through weaning: contrasted patterns
      in two nearby European regions.
AB  - This study describes infant feeding practices among mothers from two European
      regions from the perspective of early sensory experiences. Two groups of mothers,
      one in Dijon , France (n=139), the other in Aalen , Germany (n=157) with infants
      aged 4-9 months were interviewed using a structured questionnaire. Clear between-
      and within-group differences in weaning practices were found, particularly with
      respect to breastfeeding duration (Aalen>Dijon) and exposure to flavour variety
      early in weaning (Dijon>Aalen). By 4 months, 65% of infants in Dijon and 20% in
      Aalen, had received their first non-milk, solid foods. Before beginning to wean,
      39% of mothers in Dijon offered their infant a variety of foods "just for a
      taste". This was the case for only 25% of mothers in Aalen. During the first 28
      days of weaning, infants in Dijon were offered a greater number of vegetables
      compared to those in Aalen and more frequent changes from day-to-day. Thus, while
      Aalen infants were likely to be exposed for a longer period to different sensory
      experiences via breast milk, Dijon infants tended to be exposed to a greater
      flavour variety during the first weeks of weaning.

PMID- 17434648
TI  - Factors associated with lower Mini Mental State Examination scores in elderly
      Japanese diabetes mellitus patients.
AB  - Cognitive impairment in elderly diabetic patients has generated considerable
      interest recently; however, the mechanism of the impairment remains to be
      elucidated. In the current study, factors associated with cognitive dysfunction
      in old diabetic patients were explored. A Mini Mental State Examination (MMSE)
      was performed on 907 of 1173 registered elderly Japanese diabetic subjects. To
      characterize the clinical features of diabetes, we examined indices of glycemic
      control, lipid metabolism, blood pressure and complications. Single regression
      analysis adjusted for age showed that shorter height, higher GDS 15 scores, lower
      serum albumin, history of cerebrovascular disease, the existence of diabetic
      nephropathy, no smoking habit, no drinking habit, and no occupation were
      associated with lower MMSE scores. Multiple regression analysis demonstrated that
      age (odds ratio (OR)=1.079; 95% confidence interval (CI)=1.011-1.150), GDS 15
      scores (OR=1.139; 95% CI=1.045-1.243), serum albumin (OR=0.336; 95% CI=0.174
      0.745), and history of cerebrovascular disease (OR=3.011; 95% CI=1.578-5.748)
      were the variables significantly associated with having lower MMSE scores.

PMID- 17434649
TI  - Neurosteroid analogues. 12. Potent enhancement of GABA-mediated chloride currents
      at GABAA receptors by ent-androgens.
AB  - Allopregnanolone (1) and pregnanolone (2), steroids containing a 17beta-acetyl
      group, are potent enhancers of GABA (gamma-aminobutyric acid) action at GABAA
      receptors. Their effects are enantioselective with the non-naturally occurring
      enantiomers (ent-1 and ent-2) being less potent. Androsterone (3) and
      etiocholanolone (4), steroids with a C-17 carbonyl group, are weak enhancers of
      GABA action at GABAA receptors. Unexpectedly, their enantiomers (ent-3 and ent-4)
      have been found to have enhanced, not diminished, activity at GABAA receptors.
      Furthermore, the C-17 spiro-epoxide analogues (ent-5 and ent-6) of ent-3 and ent
      4, respectively, have activities comparable to those of steroids 1 and 2. The
      results indicate that some ent-steroids are potent modulators of GABAA receptors
      and might have clinical potential as GABAergic drugs of the future.

PMID- 17434650
TI  - Caffeoylglycolic and caffeoylamino acid derivatives, halfmers of L-chicoric acid,
      as new HIV-1 integrase inhibitors.
AB  - Human immunodeficiency virus (HIV) integrase (IN) catalyzes the integration of
      HIV DNA copy into the host cell DNA. L-Chicoric acid (1) has been found to be one
      of the most potent HIV-1 integrase inhibitor. Caffeoylglycolic and caffeoylamino
      acid derivatives' halfmeric structures of L-chicoric acid 2 were synthesized for
      the purpose of simplifying the structure of L-chicoric acid. Among synthesized,
      compounds 2c and 3f showed HIV-1 IN inhibitory activities with IC(50) values of
      10.5 and 12.0 microM, respectively, comparable to that of parent compound L
      chicoric acid (IC(50)=15.7 microM).

PMID- 17434651
TI  - Protective immunity of biodegradable nanoparticle-based vaccine against an
      experimental challenge with Salmonella Enteritidis in mice.
AB  - Salmonella spp. infections transmitted by contaminated poultry and eggs represent
      a major global health burden. Salmonella enterica serovar. Enteritidis is the
      leading cause of human salmonellosis worldwide. The cell surface antigens of
      Salmonella Enteritidis play an important role in the host-pathogen interactions
      and as such represent potential candidates for subunit-vaccine development. An
      immunogenic subcellular extract obtained from whole Salmonella Enteritidis cells
      (HE) was encapsulated in nanoparticles made with the polymer Gantrez (HE-NP).
      Proteomics was used to investigate the complex protein nature of the HE extract.
      Immunogenicity and protection studies against lethal Salmonella Enteritidis
      challenge were performed in BALB/c mice. Increased survival was observed in
      vaccinated mice as compared to a control group; 80% of the mice immunized with
      the HE-NP formulation survived even when administered 49 days before the lethal
      challenge. The cytokines released from in vitro-stimulated spleens showed a
      strong gamma interferon response in all immunized groups at day 10 post
      immunization. However, the immunity induced by HE-NP at day 49 post-immunization
      suggests the involvement of a TH2 subclass in the protective effect. The
      potential for mucosal vaccination suggests that HE-nanoparticles may represent an
      important alternative to the conventional attenuated vaccines against Salmonella
      Enteritidis.

PMID- 17434652
TI  - Radioecological investigations in shallow bays of the Novaya Zemlya Archipelago
      in 2002-2005.
AB  - The results of a survey of underwater disposal sites of potentially hazardous
      objects in the Kara Sea and Oga, Tsivolky, Stepovoy and Abrosimov Bays are
      presented. Radionuclide levels were determined, using gamma-spectrometric and
      radiochemical methods, in zones near to and remote from buried solid radioactive
      waste in the outer and inner parts of the Bays. At the repository of the solid
      radioactive waste containers in the inner part of the Stepovoy Bay and Abrosimov
      Bay, higher than background concentrations of (137)Cs were determined in samples
      of bottom sediments. At one of the sites located in the Stepovoy Bay (137)Cs and
      (60)Co were detected.

PMID- 17434653
TI  - Chaos, co-existence, and the potential for collective action: HIV-related
      vulnerability in Brazil's international borders.
AB  - In a country where quality HIV/AIDS prevention and care has been foremost on the
      national agenda, Brazil's extensive and diverse borders are one of the last
      unstudied potential hotbeds of HIV vulnerability. We carried out a rapid
      assessment of HIV-related services and the social context of HIV/AIDS at the
      Brazilian borders including current governmental and community response. The
      assessment was implemented in six frontier municipalities using the WHO's
      strategic approach methodology, which combines existing epidemiologic data with
      field-based qualitative data collection techniques, including observation of
      service delivery points and in-depth interviews and focus groups with local
      leaders, providers, and community members, in order to recommend context-specific
      HIV prevention strategies. This paper focuses on the qualitative findings
      regarding the role of the social context in shaping HIV vulnerability at the
      Brazilian borders. We documented a profound lack of governmental structure and
      response to HIV/AIDS at the borders as well as a notable absence of social
      cohesion and mobilization among the diverse population groups and communities
      situated at the borders with regard to HIV/AIDS. The weak governmental and
      community response is situated within a larger socio-political context of
      economic inequity and social division, which must be addressed if an effective
      response to HIV can be developed at Brazil's international borders. Possibilities
      for encouraging a collective response among the diverse border populations are
      explored.

PMID- 17434654
TI  - Evaluation of genotoxicity and pro-oxidant effect of the azo dyes: acids yellow
      17, violet 7 and orange 52, and of their degradation products by Pseudomonas
      putida mt-2.
AB  - Acids yellow 17, violet 7 and orange 52, very important commercial azo dyes used
      in the textile, food, paper and cosmetic industries, were degraded by Pseudomonas
      putida mt-2 at concentrations up to 100mg/l. The culture media was completely
      decolorized under static incubation for 60 h, this faster than under continuous
      shaking incubation. SOS chromotest using Escherichia coli PQ37, with and without
      metabolic activation (S-9 preparations), was used to assess genotoxicity
      potential of these dyes before and after biodegradation. None of these dyes or
      their metabolites was found to be genotoxic in the absence of "Araclor-Induced
      rat liver microsome" preparations (S-9). However, in presence of the preparation
      S-9, the genotoxicity of the biodegradation products was highlighted. Metabolites
      resulting from static cultures were more genotoxic than those obtained in shaken
      conditions. In addition to genotoxic effects, metabolites have shown a
      significant ability to induce the formation of superoxide free radical anion
      (O(2)(*-)). The toxicities generated by the pure azo dyes and the pure azo
      reduction products (sulfanilic acid, N,N'-dimethyl-p-phenylenediamine and 4'
      aminoacetanilid) were compared. These results suggest that P. putida mt-2
      degrades the studied azo dyes in two steps: an azo-reduction followed by an
      oxygen-dependent metabolization. Some of the derived metabolites would be
      responsible of genotoxicity and metabolic toxicity.

PMID- 17434655
TI  - Aluminium leaching using chelating agents as compositions of food.
AB  - In this work, we study aluminium (Al) leaching using three chelating agents
      (lactic acid, oxalic acid, and citric acid) that are commonly found in foods and
      beverages. We test acids, sodium, potassium and lithium salts of these three
      chelating agents. Aluminium concentrations are determined by using Graphite
      Furnace Atomic Absorption Spectrometry (GFAAS) after a one hour incubation of the
      aluminium with the chelating agent. We study three concentrations corresponding
      to the lower, median, and to the higher levels of these substances that are
      commonly found in consumable foods. We select ambient and boiling temperatures
      for the incubation. We found that at ambient temperature, the variation of Al
      leaching depends on the chemical form. Al leaching is significantly higher at 100
      degrees C than at the ambient temperature. The salty form for the composition
      releases more Al than the acidic form.

PMID- 17434656
TI  - Protective effects of organosulfur compounds towards N-nitrosamine-induced DNA
      damage in the single-cell gel electrophoresis (SCGE)/HepG2 assay.
AB  - The aim of this study was to investigate the protective effect of organosulfur
      compounds towards N-nitrosamine-induced DNA damage in the single-cell gel
      electrophoresis (SCGE)/HepG2 assay. N-Nitrosopyrrolidine (NPYR) and N
      nitrosodimethylamine (NDMA) incubated with formamidopyrimidine-DNA glycosylase
      (Fpg), caused a significant increase in oxidative DNA damage in comparison to the
      solvent control, the lowest effective concentrations, being 5 and 27 mM,
      respectively. NPYR exerted greater genotoxic effects than NDMA. None of the
      organosulfur compounds (OSCs) concentrations tested in presence or absence of Fpg
      enzyme, caused DNA damage per se. OSCs (diallyl sulfide, DAS and dipropyl
      sulfide, DPS, 1-50 microM; diallyl disulfide, DADS and dipropyl disulfide, DPDS,
      1-5 microM) reduced the genotoxic effects of the N-nitrosamines in a dose
      dependent manner when HepG2 cells were simultaneously treated with OSCs and N
      nitrosamines. The effect of NPYR was attenuated by about 61-67%, respectively,
      with the highest concentration of DAS (50 microM) and DADS (5 microM). The
      protective effect of DADS (5 microM, 66%) was higher than DAS (50 microM, 53%)
      towards NDMA-induced oxidative DNA damage. A concentration of 50 microM DPS and 5
      microM DPDS led to a 65-63% and 59-65% reduction in NPYR/NDMA-induced oxidative
      DNA damage, respectively. Our results indicate that OSCs protect human-derived
      cells against the oxidative DNA damaging effect of NPYR and NDMA, two
      carcinogenic compounds which occur in the environment.

PMID- 17434657
TI  - Opening the black box: lessons from cell-free systems on the phagocyte NADPH
      oxidase.
AB  - The NADPH-oxidase complex of phagocytic cells plays a key role in the defense
      against invading pathogens, through the release of superoxide anion, precursor of
      other reactive oxygen species (ROS). NADPH-oxidase deficiency is called Chronic
      Granulomatous Disease (CGD), in which patients suffer from recurrent infections
      and from the formation of granulomas in various organs. Research on NADPH-oxidase
      has much benefited from the discovery of cell-free systems, i.e. reconstitution
      assays from broken resting (unstimulated) phagocytes, in which activation of the
      oxidase is elicited in vitro. Cell-free systems were developed in parallel to
      studies of molecular defects of patients with CGD, both approaches leading to the
      identification of the major proteins implicated in enzyme activation. Variations
      around the cell-free system allowed molecular dissection of the mechanism of
      NADPH-oxidase activation and provided insights into its relationship to
      phagocytosis.

PMID- 17434658
TI  - A structure-based approach for targeting the HIV-1 genomic RNA dimerization
      initiation site.
AB  - Dimerization of the genomic RNA is an important step of the HIV-1 replication
      cycle. The Dimerization Initiation Site (DIS) promotes dimerization of the viral
      genome by forming a loop-loop complex between two DIS hairpins. Crystal
      structures of the DIS loop-loop complex revealed an unexpected and strong
      similitude with the bacterial 16S ribosomal aminoacyl-tRNA site (A site), which
      is the target of aminoglycoside antibiotics. As a consequence of these structural
      and sequence similarities, the HIV-1 DIS also binds some aminoglycosides, not
      only in vitro, but also ex vivo, in lymphoid cells and in viral particles.
      Crystal structures of the DIS loop-loop in complex with several aminoglycoside
      antibiotics provide a detailed-view of the DIS/drug interaction and reveal some
      hints about possible modifications to increase the drug affinity and/or
      specificity.

PMID- 17434659
TI  - Destabilised mutants of ubiquitin gain equal stability in crowded solutions.
AB  - This paper investigates the thermodynamic and kinetic response of WT* ubiquitin
      (F45W) and three mutants to high concentrations of glucose, sucrose and dextran
      under physiological temperature and pH. WT* ubiquitin was stabilised by the same
      amount when comparing each cosolute on a weight to volume ratio, with cosolute
      effects largely independent of denaturant concentration. The energy difference
      between the mutants and WT* ubiquitin also remained the same in high
      concentrations of cosolute. An apparent decrease in transition-state surface
      burial in the presence of the cosolutes was attributed to increased compaction of
      the denatured state, and not to the Hammond effect. Together, these results
      suggest higher thermodynamic stabilities and folding rates for proteins in vivo
      compared to in vitro, in addition to more compact denatured states. Because the
      effects of mutation are the same in dilute solution and crowded conditions used
      to mimic the cellular environment, there is validity in using measurements of
      mutant stabilities made in dilute solutions to inform on how the mutations may
      affect stability in vivo.

PMID- 17434660
TI  - Quantification and MRI validation of regional contractile dysfunction in mice
      post myocardial infarction using high resolution ultrasound.
AB  - A versatile, computationally efficient two-dimensional (2D) speckle-tracking
      method based on high resolution ultrasound imaging is proposed to quantify
      regional myocardial dysfunction in mice. Ultrasound scans were performed on the
      hearts of normal and post myocardial infarction (MI) mice with a Vevo770 scanner
      (VisualSonics, Toronto, Canada) operating at 30 MHz frequency. Regional
      myocardial motion was tracked using a 2D minimum sum of absolute differences
      (MSAD) block-matching algorithm. Motion analyses calculated from ultrasound
      images were compared with gold-standard analyses performed using small animal
      magnetic resonance imaging (MRI). The radial and circumferential components of
      strain were compared between ultrasound and MRI short axis views and promising
      correlations were obtained (r = 0.90 and r = 0.85 for radial and circumferential
      strain, respectively). Therefore, ultrasound imaging, followed by 2D image
      tracking, provides an effective, low cost, mobile method to quantify murine
      cardiac function accurately and reliably.

PMID- 17434661
TI  - Cavitational mechanisms in ultrasound-accelerated fibrinolysis.
AB  - The role of both inertial and stable cavitation was investigated during in vitro
      ultrasound-accelerated fibrinolysis by recombinant tissue plasminogen activator
      (rt-PA) in the presence and absence of Optison. A unique treatment configuration
      applied ultrasound, rt-PA and Optison to the interior of a plasma clot. Lysis
      efficacy was measured as clot weight reduction. Cavitational mechanisms were
      investigated by monitoring subharmonic and broadband noise. In the absence of
      Optison, 1.7 MHz pulsed ultrasound with 1.5 MPa peak-negative pressure applied
      for 30 min resulted in 45 +/- 19% lysis enhancement relative to rt-PA alone.
      Cavitation was not detected, indicating a role of noncavitational effects of
      ultrasound. The addition of Optison increased lysis enhancement to 88 +/- 25%.
      Inertial cavitation was present only at the start of the exposure, while low
      amplitude subharmonic emissions persisted throughout. Additional protocols
      suggested a possible correlation between the increased lysis in the presence of
      Optison and the subharmonic emission, indicating a potentially important role of
      stable rather than inertial cavitation in microbubble-enhanced ultrasound
      accelerated rt-PA-mediated thrombolysis.

PMID- 17434662
TI  - New echocardiographic applications for assessing global left ventricular
      diastolic function.
AB  - A number of promising and highly technological echocardiographic imaging tools
      have recently been introduced to assess left ventricular diastolic function
      (i.e., the capacity of the ventricle to relax and fill). They permit
      quantification of distinct features of intraventricular blood flow velocity and
      pressure fields and myocardial tissue velocities. However, accurate
      interpretation of the new images and clinical indices is still cumbersome, as
      basic knowledge about intraventricular hemodynamics and ventricular wall
      mechanics is often insufficient. This review article provides a comprehensive and
      original overview of the hemodynamical and mechanical events that occur during
      diastole and discusses how this new information can be used in the clinical and
      research setting to evaluate diastolic function in the healthy and the diseased
      heart. It furthermore aims to explain the underpinnings of the techniques in such
      a way that the underlying biomechanical concepts (fluid dynamics and wall
      mechanics) become less obscure to cardiologists and echocardiographers and such
      that the biomedical engineers are given some insights into the avalanche of
      diastolic performance indices that currently exist.

PMID- 17434663
TI  - Morphological and functional evaluation of murine heterotopic cardiac grafts
      using ultrasound biomicroscopy.
AB  - This study investigated the use of an ultrasound biomicroscope (UBM) to observe
      murine heterotopic cardiac transplants. By using an UBM (30 MHz), cardiac
      isografts in eight mice were studied on days 1, 5, 14 and 50 posttransplantation.
      The same method was tested in allografts in two mice on days 1, 5, 7 and 9. Two
      dimensional imaging delineated the graft structures with high spatial resolution.
      In isografts, M-mode recording showed gradually decreased left ventricular (LV)
      wall thickness and chamber dimension, but increased LV fractional shortening.
      Doppler sampling measured blood velocities from the ascending aorta, left
      coronary artery (LCA), aortic and mitral orifices of grafts. In isografts, LCA
      forward flow caused by native circulation to perfuse the graft myocardium
      increased from day 1 to 5, then moderately decreased by day 14 and stabilized
      thereafter. In allografts, LCA forward flow sharply decreased to almost zero
      between day 5-9. Therefore, UBM is a reliable method for following the survival
      status of cardiac grafts in mice.

PMID- 17434664
TI  - Discriminatory ability of calcaneal quantitative ultrasound in the assessment of
      bone status in patients with inflammatory bowel disease.
AB  - A high incidence of bone disease in patients with inflammatory bowel disease
      (IBD) requires frequent monitoring of skeletal status and, for that reason,
      evaluation of radiation-free technology is an issue of interest. Our objective
      was to appraise the parameters of calcaneal quantitative ultrasound (QUS):
      broadband ultrasound attenuation (BUA), speed of sound (SOS) and stiffness index
      (QUI), and establish their t-score values to investigate discriminatory ability
      of QUS in IBD patients with metabolic bone disease. The study included 126
      patients (Crohn's disease [n = 94] and ulcerative colitis [n = 32]), and 228 age-
      and sex-matched healthy volunteers. Bone status was evaluated on the same day by
      calcaneal QUS and dual-energy x-ray absorptiometry (DXA) at spine (L1-L4) and
      total hip. All QUS measurements were lower in patients compared with healthy
      controls (BUA p < 0.001; SOS p < 0.001; QUI p < 0.001) and correlated
      significantly but inversely with disease duration (r = -0.3, p = 0.002). There
      was no difference with respect to type of disease (Crohn's disease or ulcerative
      colitis) or corticosteroid therapy. All three QUS t-scores were significantly
      lower in patients who had previously sustained fragile fractures (n = 28) than in
      those without fracture in their history (n = 98) (t-scores: BUA -2.0 vs. -1.3, p
      = 0.008; SOS -2.1 vs. -1.4, p = 0.02: QUI -2.3 vs. -1.5, p = 0.009). Axial DXA
      was not significantly different between the fracture and nonfracture patients (
      1.7 vs. -1.2, p = 0.1), whereas total hip DXA showed a discriminatory power
      between the two (-1.6 vs. -0.7, p = 0.001). Patients with t-score < -1.0 scanned
      by DXA were classified as bone disease. The sensitivity of QUS to identify bone
      disease was 93% and specificity 63%. The sensitivity of QUS to detect osteopenia
      was 84% and 72% for osteoporosis. Alternatively, lower negative QUS t-score
      cutoff <or= -1.8 identified 83% of osteoporosis at lumbar spine and 100% at total
      hip. All three QUS variables had t-scores less than -1.8 when osteoporosis was
      detected at both spine and hip. However, the subgroup of IBD patients with QUI t
      score cutoff <or= -1.8 still included 26% of individuals with normal bone status.
      Calcaneal QUS measurements may identify patients with IBD who are at a higher
      risk of fracture independently of DXA measurements. However, QUS showed poor
      agreement with bone status scanned by DXA and a low discriminatory power between
      osteopenia and osteoporosis.

PMID- 17434665
TI  - Thermal properties and changes of acoustic parameters in an egg white phantom
      during heating and coagulation by high intensity focused ultrasound.
AB  - A polyacrylamide phantom containing egg white has been proposed previously as an
      adequate tissue-mimicking material for high intensity focused ultrasound (HIFU)
      application. In this work, we report on measurements of egg white phantom thermal
      conductivity and specific heat capacity. We measured changes in acoustical
      properties which occurred during the heating and the coagulation process. Using a
      thin thermocouple embedded in the phantom material, we recorded the temperature
      response in the focus of the ultrasound field during HIFU application and phantom
      coagulation. The measured values for the thermal conductivity (0.59 +/- 0.06 W/m/
      degrees C) and the specific heat capacity (4270 +/- 365 J/kg/ degrees C) are
      similar to the values of water. The attenuation coefficient decreased in the
      temperature range between 26 degrees C and 50 degrees C and showed a nonlinear
      dependence on frequency with an exponent of 1.50 +/- 0.05 that was temperature
      independent within the investigated temperature range. Below 65 degrees C, no
      irreversible changes in material absorption were observed. The coagulation
      process started at 67 degrees C and no adjacent rapid changes in temperature
      response were detected. In comparison with the noncoagulated phantom, the
      coagulated phantom material showed an enhanced absorption and a threefold higher
      attenuation coefficient at a frequency of 1 MHz.

PMID- 17434666
TI  - Factors affecting the arterial distension waveform derived from tissue Doppler
      imaging (TDI): an in vitro study on precision.
AB  - An investigation was made into the effect of acquisition parameters on the
      distension waveform estimated from tissue Doppler imaging (TDI). Physiological
      distension waveforms were generated using a compliant wall phantom. Distensions
      derived over a range of scanning geometries and transducer pressures were
      compared with those obtained in optimised scanning conditions. The estimated
      maximum distension decreased with scanning depth by 7% between 20 mm and 44 mm
      below the phantom surface, with an increase in transducer-vessel angle (by 22%
      from 0 degrees to 24 degrees ) and with a decrease in scan plane-vessel
      coincidence (by 34% from coincidence to 2 mm from the vessel central axis). An
      increase with transducer pressure was observed (by 20% from contact to high
      exerted pressure).

PMID- 17434667
TI  - Molecular imaging with targeted perfluorocarbon nanoparticles: quantification of
      the concentration dependence of contrast enhancement for binding to sparse
      cellular epitopes.
AB  - Targeted, liquid perfluorocarbon nanoparticles are effective agents for acoustic
      contrast enhancement of abundant cellular epitopes (e.g., fibrin in thrombi) and
      for lower prevalence binding sites, such as integrins associated with tumor
      neovasculature. In this study, we sought to delineate the quantitative
      relationship between the extent of contrast enhancement of targeted surfaces and
      the density (and concentration) of bound perfluorocarbon (PFC) nanoparticles. Two
      dramatically different substrates were utilized for targeting. In one set of
      experiments, the surfaces of smooth, flat, avidin-coated agar disks were exposed
      to biotinylated nanoparticles to yield a thin layer of targeted contrast. For the
      second set of measurements, we targeted PFC nanoparticles applied in thicker
      layers to cultured smooth muscle cells expressing the transmembrane glycoprotein
      "tissue factor" at the cell surface. An acoustic microscope was used to
      characterize reflectivity for all samples as a function of bound PFC (determined
      via gas chromatography). We utilized a formulation of low-scattering
      nanoparticles having oil-based cores to compete against high-scattering PFC
      nanoparticles for binding, to elucidate the dependence of contrast enhancement on
      PFC concentration. The relationship between reflectivity enhancement and bound
      PFC content varied in a curvilinear fashion and exhibited an apparent asymptote
      (approximately 16 dB and 9 dB enhancement for agar and cell samples,
      respectively) at the maximum concentrations (approximately 150 microg and
      approximately 1000 microg PFOB for agar and cell samples, respectively). Samples
      targeted with only oil-based nanoparticles exhibited mean backscatter values that
      were nearly identical to untreated samples (<1 dB difference), confirming the oil
      particles' low-scattering behavior. The results of this study indicate that
      substantial contrast enhancement with liquid perfluorocarbon nanoparticles can be
      realized even in cases of partial surface coverage (as might be encountered when
      targeting sparsely populated epitopes) or when targeting surfaces with locally
      irregular topography. Furthermore, it may be possible to assess the quantity of
      bound cellular epitopes through acoustic means.

PMID- 17434668
TI  - Real-time shear velocity imaging using sonoelastographic techniques.
AB  - In this paper, a novel sonoelastographic technique for estimating local shear
      velocities from propagating shear wave interference patterns (termed crawling
      waves) is introduced. A relationship between the local crawling wave spatial
      phase derivatives and local shear wave velocity is derived with phase derivatives
      estimated using an autocorrelation technique. Results from homogeneous phantoms
      demonstrate the ability of sonoelastographic shear velocity imaging to quantify
      the true underlying shear velocity distributions as verified using time-of-flight
      measurements. Heterogeneous phantom results reveal the capacity for lesion
      detection and shear velocity quantification as validated from mechanical
      measurements on phantom samples. Experimental results obtained from a prostate
      specimen illustrated feasibility for shear velocity imaging in tissue. More
      importantly, high-contrast visualization of focal carcinomas was demonstrated
      introducing the clinical potential of this novel sonoelastographic imaging
      technique.

PMID- 17434669
TI  - Volume stitching in three-dimensional echocardiography: distortion analysis and
      extension to real time.
AB  - Three-dimensional (3D) echocardiography is challenging due to limitation of the
      data acquisition rate caused by the speed of sound. ECG-gated stitching of data
      from several cardiac cycles is a possible technique to achieve higher resolution.
      The aim of this work is two-fold: it is, firstly, to provide a method for real
      time presentation of stitched echocardiographic images acquired over several
      cardiac cycles and, secondly, to demonstrate that the geometrical distortion of
      the images is decreased when stitching is applied to 3D ultrasonic data of the
      left ventricle (LV). We present a volume stitching algorithm that merges data
      from N consecutive heart cycles into an assembled data volume. The assembly is
      performed in real time, making immediate volume rendering of the full volume
      possible. In-vivo images acquired with this technique are presented. Through
      simulations with a kinematic model of the LV wall, geometrical distortion and
      volume estimation errors due to long image capture time was quantified for 3D
      recordings of the LV. Curves showing the variation throughout the cardiac cycle
      of the maximal geometrical distortion in the LV walls are presented, as well as
      curves showing the volume estimates compared with the true LV volume of the
      model. We conclude that real-time display of stitched 3D ultrasound data is
      feasible and that it is an adequate technique for increasing the volume
      acquisition rate at a given spatial resolution. Furthermore, the geometrical
      distortion decreases substantially for data with higher volume rate and, for a
      full scan of the LV, stitching over at least four cycles is recommended.

PMID- 17434670
TI  - Editorial comment on: laparoscopic radioisotope-guided sentinel lymph node
      dissection in staging of prostate cancer.

PMID- 17434671
TI  - Editorial comment on: laparoscopic radioisotope-guided sentinel lymph node
      dissection in staging of prostate cancer.

PMID- 17434672
TI  - Laparoscopic radioisotope-guided sentinel lymph node dissection in staging of
      prostate cancer.
AB  - OBJECTIVES: To present our experience in laparoscopic sentinel lymph node (SLN)
      dissection in staging of clinically localized prostate cancer. METHODS: From
      November 2001 to January 2005 laparoscopic SLN dissection was performed in 140
      patients with clinically localized prostate cancer preceding radical
      prostatectomy. Mean preoperative prostate-specific antigen (PSA) level was 8.26
      ng/ml (SD 9.46). At 24 h before surgery, 2 ml 99mTc-labeled human albumin (2
      ml/200 MBq) colloid was injected into the prostate gland under transrectal
      ultrasound guidance. Prostatic SLNs were detected by preoperative planar
      scintigraphy and intraoperative scanning with a specially designed laparoscopic
      gamma probe. The detected nodes were dissected and evaluated on frozen section.
      In case of positive frozen section extended lymph node dissection was performed.
      RESULTS: SLN was identified on both or one pelvic sidewall in 96 (68.1%) and 36
      (25.7%) of the patients, respectively. SLNs were undetectable in 8 (5.7%) cases.
      In 48.2% (135 of 280) of the pelvic sidewalls, SLNs were exclusively outside the
      obturator fossa. Final histopathologic examination revealed SLN metastases in 19
      (13.5%) patients; 71.4% (20 of 28) of the detected metastases were outside the
      current standard of lymph node dissection limited to the obturator fossa. Mean
      tumor size was 2.3 mm (SD 1.7). CONCLUSIONS: Our data confirm the reliability of
      laparoscopic SLN dissection in staging of prostate cancer. Significant numbers of
      detected metastases were outside of the routinely sampled obturator fossa. Small
      metastasis size makes them undetectable by currently available preoperative
      imaging modalities.

PMID- 17434673
TI  - Nerve growth factor in serum is a marker of the stage of alcohol disease.
AB  - Long-term alcohol abuse has deleterious effects on the peripheral and central
      nervous system. Nerve growth factor (NGF) is a pleiotropic neurotrophic protein
      involved in development, maintenance of function and regeneration of nerve cells.
      We examined patients in different stages of alcohol disease and measured their
      NGF serum concentrations based on the hypothesis that these reflect the state of
      disease. We examined 57 patients suffering from alcohol-dependence for more than
      2 years (DSM IV) on day 8 of a qualified withdrawal, 18 patients with Korsakoff's
      syndrome and 40 healthy controls. In addition to clinical examination, careful
      history taking and a standard neuropsychological test battery, serum NGF
      concentrations were measured by a highly sensitive enzyme-immunoassay. Of the 57
      patients 9 had suffered from severe withdrawal delirium in the past, other
      clinical parameters were alike. Cognitive test performance did not differ from
      the control group. Mean NGF levels of controls amounted to 42.1pg/ml (S.D. 68.0);
      mean levels of patients with alcohol dependence were raised significantly to
      401.5pg/ml (S.D. 932.6) without delirium in the past and even further to
      3292.5pg/ml (S.D. 4879.6) with former withdrawal delirium. By contrast, patients
      with persistent amnestic disorder (Korsakoff's syndrome) showed values identical
      to the controls. NGF serum levels were significantly elevated in alcohol
      dependent patients, more so in those with prior delirium. Their cognitive tests
      being normal, this possibly reflects the activity of NGF as an endogenous repair
      mechanism for damaged neurons. In accordance with this hypothesis, NGF values are
      "normal" in patients with persistent alcohol-related cognitive decline.

PMID- 17434675
TI  - General three-dimensional image simulation and surface reconstruction in scanning
      probe microscopy using a dexel representation.
AB  - The ability to image complex general three-dimensional (3D) structures, including
      reentrant surfaces and undercut features using scanning probe microscopy, is
      becoming increasing important in many small length-scale applications. This paper
      presents a dexel data representation and its algorithm implementation for
      scanning probe microscope (SPM) image simulation (morphological dilation) and
      surface reconstruction (erosion) on such general 3D structures. Validation using
      simulations, some of which are modeled upon actual atomic force microscope data,
      demonstrates that the dexel representation can efficiently simulate SPM imaging
      and reconstruct the sample surface from measured images, including those with
      reentrant surfaces and undercut features.

PMID- 17434674
TI  - Role of spinal metabotropic glutamate receptors in regulation of lower urinary
      tract function in the decerebrate unanesthetized rat.
AB  - The role of spinal metabotropic glutamate receptors (mGluRs) in control of lower
      urinary tract functions was evaluated in rats using an mGluR antagonist
      administered via the intrathecal route. Cystometrograms in combination with
      external urethral sphincter (EUS) EMG recordings were performed on 13 decerebrate
      unanesthetized Sprague-Dawley female rats (n=6 for spinal cord intact rats; n=7
      for spinal cord transected rats). In spinal cord intact rats, a group I/II mGluR
      antagonist, (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG), at doses of 3-30
      microg, changed neither bladder nor EUS EMG activity, whereas a larger dose (100
      microg) produced a significant facilitation of EUS EMG activity (41% increase in
      the peak activity) with little effect on bladder contractions. In chronically
      spinal cord transected rats, MCPG (3-100 microg) had no effect on bladder and EUS
      EMG activity. The results suggest that group I/II mGluRs are likely to be
      involved in inhibition of the excitatory pathway to the EUS but not involved in
      the control of the bladder. The lack of effect of MCPG on the EUS EMG activity in
      chronic spinal cord transected rats indicates that mGluR-mediated inhibitory
      control of the EUS was eliminated after spinal cord injury.

PMID- 17434676
TI  - Influence of Ascaridia galli infections and anthelmintic treatments on the
      behaviour and social ranks of laying hens (Gallus gallus domesticus).
AB  - In the present study, the effects of an experimental Ascaridia galli infection
      and anthelmintic treatment on the behaviour and social status of laying hens of
      two different lines were studied. Sixty white (Lohmann LSL; LSL) and 60 brown
      (Lohmann Brown; LB) hens were reared under helminth-free conditions. The hens of
      each line were divided into four groups. The birds in two of the groups were
      artificially infected with 250 embryonated A. galli eggs at an age of 27 weeks.
      The other two groups were kept as uninfected controls. One infection and control
      group was dewormed at 38 weeks of age and slaughtered 4 weeks later, contemporary
      with the other animals. Individual faecal Ascaridia egg counts (FEC) were
      performed 11 weeks post-infection (p.i.). Body weights, laying performance and
      egg weights were recorded regularly. Blood was taken to measure testosterone
      levels. The worm burdens established in the intestines were counted in the
      infected not treated group after slaughtering. In addition, 15 behavioural
      parameters were recorded by focal animal observation (n=10 per group) of one
      infection (plus anthelmintic treatment) and one control group, according to the
      time-sampling method throughout the experiment. All agonistic interactions within
      the groups were recorded simultaneously on an ongoing basis, thereby allowing the
      calculation of an individual social rank index. The following results were
      obtained: Mean FEC and worm burden were higher (p < 0.01) in the LSL hens than in
      the LB hens, but their performances were not different (p > 0.05) from the
      controls. Infections with A. galli resulted in significant behavioural changes in
      both lines as the infected birds showed a higher food intake and lower locomotion
      activity during the prepatent and patent periods. After anthelmintic treatment,
      food intake decreased and locomotion increased. Behavioural changes were more
      pervasive in the infected LSL hens, as these hens also showed changes in ground
      pecking and nesting activity not only during the prepatent and patent periods,
      but also after anthelmintic treatment. Social rank did not significantly change
      as a consequence of A. galli infection, but the infection groups of both lines
      had a tendency to display more agonistic activity than the non-infected controls.
      Serum testosterone values only increased significantly in the LSL hens during the
      patent period compared to the controls. No significant correlations were apparent
      between serum testosterone level, parasitic parameters, social status and/or
      aggressiveness in any of the groups. This study showed that even sub-clinical A.
      galli infections and their anthelmintic treatment can have an impact on animal
      behaviour.

PMID- 17434677
TI  - Molecular recognition of DNA by small molecules: AT base pair specific
      intercalative binding of cytotoxic plant alkaloid palmatine.
AB  - The base dependent binding of the cytotoxic alkaloid palmatine to four synthetic
      polynucleotides, poly(dA).poly(dT), poly(dA-dT).poly(dA-dT), poly(dG).poly(dC)
      and poly(dG-dC).poly(dG-dC) was examined by competition dialysis,
      spectrophotometric, spectrofluorimetric, thermal melting, circular dichroic,
      viscometric and isothermal titration calorimetric (ITC) studies. Binding of the
      alkaloid to various polynucleotides was dependent upon sequences of base pairs.
      Binding data obtained from absorbance measurements according to neighbour
      exclusion model indicated that the intrinsic binding constants decreased in the
      order poly(dA).poly(dT)>poly(dA-dT).poly(dA-dT)>poly(dG-dC).poly(dG
      dC)>poly(dG).poly(dC). This affinity was also revealed by the competition
      dialysis, increase of steady state fluorescence intensity, increase in
      fluorescence quantum yield, stabilization against thermal denaturation and
      perturbations in circular dichroic spectrum. Among the polynucleotides,
      poly(dA).poly(dT) showed positive cooperativity at binding values lower than
      r=0.05. Viscosity studies revealed that in the strong binding region, the
      increase of contour length of DNA depended strongly on the sequence of base pairs
      being higher for AT polymers and induction of unwinding-rewinding process of
      covalently closed superhelical DNA. Isothermal titration calorimetric data showed
      a single entropy driven binding event in the AT homo polymer while that with the
      hetero polymer involved two binding modes, an entropy driven strong binding
      followed by an enthalpy driven weak binding. These results unequivocally
      established that the alkaloid palmatine binds strongly to AT homo and hetero
      polymers by mechanism of intercalation.

PMID- 17434678
TI  - Suppression of 5-lipoxygenase gene is involved in triptolide-induced apoptosis in
      pancreatic tumor cell lines.
AB  - Pancreatic adenocarcinoma is characterized by a poor prognosis and lack of
      response to conventional therapy. The purpose of this study was to investigate
      the effects of triptolide (TL) on proliferation and apoptosis of pancreatic
      cancer cells in vitro. We found that TL induced prominent growth inhibition and
      apoptosis in human pancreatic cell lines. In addition, TL treatment significantly
      down-regulated 5-lipoxygenase (5-LOX) expression, as well as downstream
      leukotriene B4 (LTB4) production, in these cell lines. Furthermore,
      overexpression of 5-LOX in SW1990 cell lines or exogenous LTB4 made them more
      resistant to TL-induced apoptosis, which was correlated with increased Bcl-2
      expression. Taken together, these findings suggest that inhibition of the 5-LOX
      pathway of arachidonic acid metabolism is associated with the anti-proliferation
      activity of TL. We also provide evidence that TL has clinical therapeutic value
      for patients with pancreatic cancer.

PMID- 17434679
TI  - Effects of chronic neonatal nicotine exposure on nicotinic acetylcholine receptor
      binding, cell death and morphology in hippocampus and cerebellum.
AB  - Nicotine, the major psychoactive ingredient in tobacco interacting with nicotinic
      acetylcholine receptors (nAChR), is believed to have neuroprotective and
      neurotoxic effects on the developing brain. Neurotoxicity has been attributed to
      activation of homomeric alpha7 nAChRs, neuroprotection to heteromeric alpha4beta2
      nAChRs. Thus, developmental nicotine could have opposite effects in different
      brain regions, depending on nAChR subtype expression. Here, we determined if
      chronic neonatal nicotine exposure (CNN), during a period of brain growth
      corresponding to the third human trimester, differentially regulates nAChR
      expression, cell death, and morphological properties in hippocampus and
      cerebellum, two structures maturing postnatally. Rat pups were orally treated
      with 6 mg/kg/day nicotine from postnatal day (P)1 to P7. On P8, expression for
      alpha4, alpha7 and beta2 mRNA was determined by in situ hybridization; nAChR
      binding sites by receptor autoradiography, dying neurons by TUNEL and Fluoro-Jade
      staining and morphological properties by analysis of Cresyl Violet-stained
      sections. In control cerebellum, strong expression of alpha4, beta2 mRNA and
      heteromeric nAChRs labeled with [125I]-epibatidine was found in granule cells,
      and alpha7 mRNA and homomeric nAChRs labeled with [125I]-alpha-bungarotoxin were
      in the external germinal layer. In control hippocampus, low expression of alpha4
      mRNA and heteromeric nAChRs and high expression of alpha7 mRNA and homomeric
      nAChRs were detected. CNN increased heteromeric nAChR binding in hippocampus but
      not cerebellum and significantly decreased neuronal soma size and increased
      packing density in hippocampal principal cells but not in cerebellum. CNN did not
      increase the number of dying cells in any area, but significantly fewer TUNEL
      labeled cells were found in CA3 strata oriens and radiatum and cerebellar granule
      layer. Thus, the hippocampus seems to be more sensitive than the cerebellum to
      CNN which could result from different nAChR subtype expression and might explain
      long-lasting altered cognitive functions correlated with gestational nicotine
      exposure due to changes in hippocampal cell morphology.

PMID- 17434681
TI  - 5-HT2 and 5-HT3 receptors in the lateral parabrachial nucleus mediate opposite
      effects on sodium intake.
AB  - The present study investigated the role of several 5-HT receptor subtypes in the
      lateral parabrachial nucleus (LPBN) in the control of sodium appetite (i.e. NaCl
      consumption). Male Holtzman rats had cannulas implanted bilaterally into the LPBN
      for the injection of 5-HT receptor agonists and antagonists in conjunction with
      either acute fluid depletion or 24-h sodium depletion. Following these
      treatments, access to 0.3 M NaCl was provided and the intakes of saline and water
      were measured for the next 2 h. Bilateral injections of the 5-HT2A receptor
      antagonist, ketanserin or the 5-HT2C receptor antagonist, mianserin into the LPBN
      increased 0.3 M NaCl intake without affecting water intake induced by acute fluid
      depletion. Bilateral injections of the 5-HT2B receptor agonist, BW723C86
      hydrochloride, had no effect on 0.3 M NaCl or water intake under these
      conditions. Treatment of the LPBN with the 5-HT2B/2C receptor agonist, 2-(2
      methyl-4-clorophenoxy) propanoic acid (mCPP) caused dose-related reductions in
      0.3 M NaCl intake after 24 h sodium depletion. The effects of mCPP were prevented
      by pretreating the LPBN with the 5-HT2B/2C receptor antagonist, SDZSER082.
      Activation of 5-HT3 receptors by the receptor agonist, 1-phenylbiguanide (PBG)
      caused dose-related increases in 0.3 M NaCl intake. Pretreatment of the LPBN with
      the 5-HT3 receptor antagonist, 1-methyl-N-[8-methyl-8-azabicyclo (3.2.1)-oct-3
      yl]-1H-indazole-3-carboxamide (LY-278,584) abolished the effects of PBG, but LY
      278,584 had no effects on sodium or water intake when injected by itself. PBG
      injected into the LPBN did not alter intake of palatable 0.06 M sucrose in fluid
      replete rats. The results suggest that activation of the 5-HT2A and 5-HT2C
      receptor subtypes inhibits sodium ingestion. In contrast, activation of the 5-HT3
      receptor subtype increases sodium ingestion. Therefore, multiple serotonergic
      receptor subtypes in the LPBN are implicated in the control of sodium intake,
      sometimes by mediating opposite effects of 5-HT. The results provide new
      information concerning the control of sodium intake by LPBN mechanisms.

PMID- 17434680
TI  - Effect of tricyclodecan-9-yl potassium xanthate (D609) on phospholipid metabolism
      and cell death during oxygen-glucose deprivation in PC12 cells.
AB  - Alterations in lipid metabolism play an integral role in neuronal death in
      cerebral ischemia. Here we used an in vitro model, oxygen-glucose deprivation
      (OGD) of rat pheochromocytoma (PC12) cells, and analyzed changes in
      phosphatidylcholine (PC) and sphingomyelin (SM) metabolism. OGD (4-8 h) of PC12
      cells triggered a dramatic reduction in PC and SM levels, and a significant
      increase in ceramide. OGD also caused increases in phosphatidylcholine
      phospholipase C (PC-PLC) and phospholipase D (PLD) activities and PLD2 protein
      expression, and reduction in cytidine triphosphate:phosphocholine
      cytidylyltransferase-alpha (CCTalpha, the rate-limiting enzyme in PC synthesis)
      protein expression and activity. Phospholipase A2 activity and expression were
      unaltered during OGD. Increased neutral sphingomyelinase activity during OGD
      could account for SM loss and increased ceramide. Surprisingly, treatment with PC
      PLC inhibitor tricyclodecan-9-yl potassium xanthate (D609) aggravated cell death
      in PC12 cells during OGD. D609 was cytotoxic only during OGD; cell death could be
      prevented by inclusion of sera, glucose or oxygen. During OGD, D609 caused
      further loss of PC and SM, depletion of 1,2-diacylglycerol (DAG), increase in
      ceramide and free fatty acids (FFA), cytochrome c release from mitochondria,
      increases in intracellular Ca2+ ([Ca2+]i), poly-ADP ribose polymerase (PARP)
      cleavage and phosphatidylserine externalization, indicative of apoptotic cell
      death. Exogenous PC during OGD in PC12 cells with D609 attenuated PC, SM loss,
      restored DAG, attenuated ceramide levels, decreased cytochrome c release, PARP
      cleavage, annexin V binding, attenuated the increase in [Ca2+]i, FFA release, and
      significantly increased cell viability. Exogenous PC may have elicited these
      effects by restoring membrane PC levels. A tentative scheme depicting the
      mechanism of action of D609 (inhibiting PC-PLC, SM synthase, PC synthesis at the
      CDP-choline-1,2-diacylglycerol phosphocholine transferase (CPT) step and causing
      mitochondrial dysfunction) has been proposed based on our observations and
      literature.

PMID- 17434682
TI  - Proteinase-activated receptors 1 and 2 in rat olfactory system: layer-specific
      regulation of multiple signaling pathways in the main olfactory bulb and
      induction of neurite retraction in olfactory sensory neurons.
AB  - Proteinase-activated receptors (PARs) are a family of four G protein-coupled
      receptors that are widely distributed in the CNS and involved in neural cell
      proliferation, differentiation and survival. The olfactory system undergoes
      continuous neurogenesis throughout life and may represent a critical target of
      PAR cellular actions. In the present study we investigated the functional
      activity of PAR1 and PAR2 in microdissected tissue preparations of olfactory
      nerve-glomerular layer (ON-GL), external plexiform layer (EPL) and granule cell
      layer (GRL) of the rat main olfactory bulb and in primary cultures of olfactory
      neuroepithelial cells. Activation of either PAR1 or PAR2 regulated multiple
      signaling pathways, including activation of pertussis-toxin sensitive Gi/o
      proteins, inhibition of cyclic AMP formation, stimulation of Gq/11-mediated
      phosphoinositide (PI) hydrolysis, phosphorylation of Ca2+/calmodulin-dependent
      protein kinase II and activation of the monomeric G protein Rho, predominantly in
      ON-GL, whereas only activation of Rho was detected in the deeper layers.
      Olfactory nerve lesion by nasal irrigation with ZnSO4 induced a marked decrease
      of PAR signaling in ON-GL. In primary cultures of olfactory neurons, double
      immunofluorescence analysis showed the localization of PAR1 and PAR2 in cells
      positive for olfactory-marker protein and neuron-specific enolase. Cell exposure
      to either nanomolar concentrations of thrombin and trypsin or PAR-activating
      peptides caused rapid neurite retraction. This study provides the first
      characterization of the laminar distribution of PAR1 and PAR2 signaling in rat
      olfactory bulb, demonstrates the presence of the receptors in olfactory sensory
      neurons and suggests a role of PARs in olfactory sensory neuron neuritogenesis.

PMID- 17434683
TI  - Postnatal upregulation of alpha4 and alpha3 nicotinic receptor subunits in the
      brain of alpha7 nicotinic receptor-deficient mice.
AB  - The nicotinic receptor subtypes are important for several physiological functions
      in brain and may therefore play a critical role in brain development. The alpha7
      nicotinic receptors which have high Ca2+ permeability are important for
      cognitive, neuroprotective and trophic functions. In this study, the brain
      development and the expression of alpha4, alpha3, alpha7, alpha5 and beta2
      nicotinic receptors were investigated in the brains of alpha7 deficient (alpha7 
      /-), alpha7 heterozygous null (alpha7 +/-) and alpha7 wild-type (alpha7 +/+) mice
      from postnatal days (P) 7-84. The specific binding of [3H] cytisine and [3H]
      epibatidine, as well as the expressions of alpha4 and alpha3 nicotinic receptor
      subunits at mRNA and protein levels, were significantly increased in the cortex
      and hippocampus of alpha7 -/- and alpha7 +/- mice compared with alpha7 +/+ mice.
      Furthermore, the alpha4 and alpha3 nicotinic acetylcholine receptor (nAChR)
      subunits appeared to co-assemble with the alpha5 nAChR subunit in these above
      brain regions of these mice. No significant change in synaptophysin level was
      observed. These data suggest that increased levels of alpha4, alpha3-containing
      nAChRs, co-assembled with the alpha5 nAChR subunit, may contribute to the normal
      brain development of alpha7 -/- and alpha7 +/- mice.

PMID- 17434685
TI  - Ischemic preconditioning enhances neurogenesis in the subventricular zone.
AB  - Ischemic preconditioning (IPC) before subsequent prolonged ischemia is considered
      an emerging endogenous means of ischemic brain protection. We tested whether IPC
      induces endogenous neurogenesis in the subventricular zone (SVZ) and angiogenesis
      in the peri-ischemic area. Middle cerebral artery occlusion was administered to
      rats by filament insertion for 10 min (IPC) and/or 2 h (prolonged focal ischemia
      [PFI]). IPC alone increased 5'-bromo-2'-deoxyuridine (BrdU) (+) cells 2.5-fold in
      the SVZ compared with controls at 7 days. The numbers of BrdU/doublecortin (Dcx)
      or BrdU/neuronal nuclei (NeuN) double-labeled cells also increased, but extents
      of BrdU/glial fibrillary acidic protein (GFAP) double-labeling in the SVZ were
      not different. The IPC+PFI group showed about a 40% reduction in infarct volume.
      PFI increased BrdU (+) cells in the SVZ, and this was greatly enhanced by IPC
      treatment. The number of BrdU/Dcx double-labeled cells was strongly increased in
      ischemic brains administered IPC. Differentiation into mature neurons was also
      enhanced at 14 and 28 days. In addition, IPC significantly promoted angiogenesis
      in the ischemic penumbra as indicated by von Willebrand factor (vWF) staining.
      Our results indicate that IPC enhances neurogenesis in the SVZ even without
      subsequent PFI, and also enhances neurogenesis and angiogenesis after subsequent
      PFI. We conclude that IPC confers neuroprotection, and also promotes endogenous
      neurogenesis and angiogenesis.

PMID- 17434684
TI  - Oral haloperidol or risperidone treatment in rats: temporal effects on nerve
      growth factor receptors, cholinergic neurons, and memory performance.
AB  - First and second generation antipsychotics (FGAs and SGAs) ameliorate psychotic
      symptoms of schizophrenia, however, their chronic effects on information
      processing and memory function (i.e. key determinants of long term functional
      outcome) are largely unknown. In this rodent study the effects of different time
      periods (ranging from 2 weeks to 6 months) of oral treatment with the FGA,
      haloperidol (2.0 mg/kg/day), or the SGA, risperidone (2.5 mg/kg/day) on a water
      maze repeated acquisition procedure, the levels of nerve growth factor receptors,
      and two important cholinergic proteins, the vesicular acetylcholine transporter
      and the high affinity choline transporter were evaluated. The effects of the
      antipsychotics on a spontaneous novel object recognition procedure were also
      assessed during days 8-14 and 31-38 of treatment. Haloperidol (but not
      risperidone) was associated with impairments in water maze hidden platform trial
      performance at each of the time periods evaluated up to 45 days, but not when
      tested during days 83-90. In contrast, risperidone did not impair water maze task
      performance at the early time periods and it was actually associated with
      improved performance during the 83-90 day period. Both antipsychotics, however,
      were associated with significant water maze impairments during the 174-180 day
      period. Further, haloperidol was associated with decrements in short delay
      performance in the spontaneous novel object recognition task during both the 8-14
      and 31-38 day periods of treatment, while risperidone was associated with short
      delay impairment during the 31-38 day time period. Both antipsychotics were also
      associated with time dependent alterations in the vesicular acetylcholine
      transporter, the high affinity choline transporter, as well as tyrosine kinase A,
      and p75 neurotrophin receptors in specific brain regions. These data from rats
      support the notion that while risperidone may hold some advantages over
      haloperidol, both antipsychotics can produce time-dependent alterations in
      neurotrophin receptors and cholinergic proteins as well as impairments in the
      performance of tasks designed to assess spatial learning and episodic memory.

PMID- 17434686
TI  - Induction of neurite outgrowth in PC12 cells by the medium-chain fatty acid
      octanoic acid.
AB  - It has been shown that polyunsaturated fatty acids such as arachinonic and
      docosahexanoic acids but not monounsaturated and saturated long-chain fatty acids
      promote basal and nerve growth factor (NGF)-induced neurite extension of PC12
      cells, a line derived from a rat pheochromocytoma. On the other hand, short-chain
      fatty acids and valproic acid (2-propylpentanoic acid) enhance the growth of
      neurite processes of the cells only in the presence of inducers. In this study,
      we demonstrated that straight medium-chain fatty acids (MCFAs) at millimolar
      concentrations alone potently induced neuronal differentiation of PC12 cells.
      Hexanoic, heptanoic and octanoic acids dose-dependently induced neurite outgrowth
      of the cells: their maximal effects determined 2 days after addition to the
      culture medium were more marked than the effect of NGF. PC12 cells exposed to
      octanoic acid expressed increased levels of the neuronal marker beta-tubulin
      isotype III. Nonanoic, decanoic, and dodecanoic acids also induced growth of
      neurite processes, but their maximal effects were less marked than that of
      octanoic acid. In contrast, the polyunsaturated fatty acid linoleic acid and
      short-chain fatty acids had only slight or almost no effects on neurite formation
      in the absence of NGF. The effect of octanoic acid was synergistic with or
      additive to the effects of NGF and dibutyryl cyclic AMP. Octanoic acid
      upregulated phosphorylation of p38 mitogen-activated protein kinase (MAPK),
      extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK),
      critical signaling molecules in neuronal differentiation, but not phosphorylation
      of Akt, a signaling molecule downstream of phosphatidylinositol 3-kinase (PI3K).
      Moreover, growth of neurites induced by octanoic acid was potently inhibited by
      treatment of cells with the p38 MAPK inhibitor SB203580 and the ERK kinase
      inhibitor PD98059 but not inhibited and only slightly inhibited by the JNK
      inhibitor SP600125 and the PI3K inhibitor wortmannin, respectively. Taken
      together, our results indicate that MCFAs, including octanoic acid, induced
      neurite outgrowth of PC12 cells in the absence of NGF and suggest that the
      activation of p38 MAPK and ERK pathways is involved in this process.

PMID- 17434687
TI  - Development and initial validation of the Worry-Reduction Alcohol Expectancy
      Scale.
AB  - Recent research on the relation between generalized anxiety and heavy drinking
      highlighted a need for a measure of worry-reduction alcohol expectancies. The
      current study aimed to develop and to assess the psychometric properties of the
      Worry-Reduction Alcohol Expectancy Scale. The development and initial validation
      of the WRAES occurred across two phases with two separate non-clinical
      undergraduate samples. Phase I was focused on scale construction and item
      selection, while Phase II included an assessment of the WRAES' reliability,
      validity and cross-validation of factor structure. Results from both study phases
      support a two-factor model. Cronbach's alpha for the total scale was .96 and
      Pearson r test-retest reliability was .75. Additionally, the mean correlation
      between the WRAES and convergent measures was significantly higher than the mean
      correlation between the WRAES and discriminant measures. Overall, the results
      provide initial support for the WRAES as a measure of worry-reduction alcohol
      expectancies.

PMID- 17434688
TI  - Co-morbidity and cannabis use in a mental health trust in South East England.
AB  - AIM: The prevalence of co-morbidity (severe mental illness and substance) may be
      less in rural and semi-rural areas than inner cities. The aims were therefore to
      measure the prevalence of co-morbidity among patients of attending a mental
      health service in a semi-rural area South East England. DESIGN AND PARTICIPANTS:
      Cross-sectional prevalence survey of 1,808 patients with detailed assessments
      from a representative sample of 373 patients identified as having a combination
      of severe mental illness and substance misuse. Interviews with key workers were
      performed using validated methods from the COSMIC study. RESULTS: The response
      rates equalled or exceeded 90% for the various parts of the study. One-tenth of
      patients attending the Community Mental Health Teams (CMHTs) reported problematic
      use of illicit drugs and 17% reported alcohol problems in the past year. 22% of
      Community Drug and Alcohol Service (CDAS) clients reported a severe mental
      illness and 46% reported some other form of psychiatric disorder. Of patients
      with a combined diagnosis of mental illness and substance misuse, cannabis use
      was 4-fold more common amongst patients attending the CMHT than CDAS (33% vs. 8%)
      while use of amphetamine was five-fold higher in the CMHT group (10% vs. 2%).
      Patients with concurrent psychiatric and substance misuse problems represent a
      similar proportion of the aggregate caseload of both treatment services with
      observed prevalence amongst the CDAS and CMHT patients with a diagnosis for
      anxiety disorder (18% vs. 26%), minor depression (42% vs. 32%), personality
      disorders (32% vs. 36%), histories of self-harm (52% vs. 46%) and violence (33%
      vs. 30%) respectively. CONCLUSIONS: Co-morbidity is common in clients amongst
      CMHT and CDAS clients although use of cannabis was significantly more common in
      CMHT clients than in CDAS clients.

PMID- 17434689
TI  - The influence of sex, line, and fight experience on aggressiveness of the Siamese
      fighting fish in intrasexual competition.
AB  - We examined the influence of sex, line, i.e., broods from different parents, and
      previous fight experience on the aggressiveness of the Siamese fighting fish
      Betta splendens in intrasexual competition. The innate aggressiveness of the fish
      against their mirror images was measured on the day prior to the direct fight
      with other individuals, and it was found to be influenced by the line type but
      not by the sex. In the direct fight with other individuals, the males invested
      more effort in the fight than the females. In addition, the individuals of a
      particular line that exhibited a lower innate aggressiveness spent less time in
      the direct fight and were often losers when compared with those of other lines.
      After the direct fight with other individuals, the aggressiveness of the fish
      against their mirror images was remarkably influenced by the outcome of the
      direct fight, i.e., the winners exhibited more aggressive behavior, whereas the
      losers exhibited a lesser degree of aggressive behavior. This influence of the
      previous fight experience on subsequent aggressiveness was the greatest in the
      individuals of the line that have exhibited the lowest innate aggressiveness.
      However, the positive effect of the winning experience or the negative effect of
      the losing experience on subsequent aggressiveness decreased following several
      days after the previous fight increased.

PMID- 17434691
TI  - Determination of the minimal acid-inducible promoter region of the lipF gene from
      Mycobacterium tuberculosis.
AB  - The Mycobacterium tuberculosis gene lipF, Rv3487c, is transcriptionally
      upregulated by exposure to acidic growth media. We previously identified a 477
      base pair (bp) region of DNA 147 bp upstream of lipF that is transcriptionally
      upregulated by exposure to growth media at pH 4.5 [Saviola, B., Woolwine, S.,
      Bishai, W. R., 2003. Isolation of acid-inducible genes of Mycobacterium
      tuberculosis with the use of recombinase-based in vivo expression technology.
      Infect. Immun. 71, 1379-1388]. In this study we truncate the lipF promoter region
      first from the 3' DNA end and then from the 5' DNA end. The truncated promoter
      regions were placed upstream of the gene for the green fluorescent protein (gfp)
      and each promoter region was analyzed in Mycobacterium smegmatis for its ability
      to undergo transcriptional upregulation in response to acid stress. A minimal
      acid-inducible promoter region was identified and is located between -515 bp and 
      573 bp with respect to the start site of translation of lipF. The 59 bp minimal
      promoter region is a defined DNA sequence that confers full promoter activity
      that is transcriptionally upregulated in response to acid stress. Primer
      extension analysis was performed on acid-induced M. smegmatis bearing the minimal
      promoter region fused to gfp and revealed a start site of transcription
      specifically upregulated by acid stress corresponding to -511 bp upstream of lipF
      with respect to the start of translation.

PMID- 17434690
TI  - Impaired time perception and motor timing in stimulant-dependent subjects.
AB  - Stimulant-dependent individuals (SDI) have abnormal brain metabolism and
      structural changes involving dopaminergic target areas important for the
      processing of time. These individuals are also more impulsive and impaired in
      working memory and attention. The current study tested whether SDI show altered
      temporal processing in relation to impulsivity or impaired prefrontal cortex
      functioning. We employed a series of timing tasks aimed to examine time
      processing from the milliseconds to multiple seconds range and assessed cognitive
      function in 15 male SDI and 15 stimulant-naive individuals. A mediation analysis
      determined the degree to which impulsivity or executive dysfunctions contributed
      to group differences in time processing. SDI showed several abnormal time
      processing characteristics. SDI needed larger time differences for effective
      duration discrimination, particularly for intervals of around 1s. SDI also
      accelerated finger tapping during a continuation period after a 1Hz pacing
      stimulus was removed. In addition, SDI overestimated the duration of a relatively
      long time interval, an effect which was attributable to higher impulsivity. Taken
      together, these data show for the first time that SDI exhibit altered time
      processing in several domains, one which can be explained by increased
      impulsivity. Altered time processing in SDI could explain why SDI have difficulty
      delaying gratification.

PMID- 17434692
TI  - A new system for analyzing LINE retrotransposition in the chicken DT40 cell line
      widely used for reverse genetics.
AB  - Long interspersed elements (LINEs) are autonomous transposable elements that
      proliferate via retrotransposition, which involves reverse transcription of LINE
      RNAs. It is anticipated that LINE retrotransposition requires both LINE-encoded
      proteins and host-encoded proteins. However, identification of the host factors,
      their roles, and the steps at which they act on retrotransposition are poorly
      understood because of the lack of an appropriate genetic system to study LINE
      retrotransposition in a series of mutant hosts. To construct such a genetic
      system, we applied the retrotransposition-indicative cassette method to DT40
      cells, a chicken cell line for which a variety of isogenic mutants have been
      established by gene targeting. Because DT40 cells are non-adherent, we utilized a
      selective soft agarose medium to allow the formation of colonies of cells that
      had undergone LINE retrotransposition. Colony formation was completely dependent
      on the activities of the LINE-encoded proteins and on the presence of the
      essential 3' region of the LINE RNA. Moreover, the selected colonies indeed
      carried retrotransposed LINE copies in their chromosomes, with integration
      features similar to those of genomic (native) LINE copies. This method thus
      allows the authentic selection of LINE-retrotransposed cells and the approximate
      recapitulation of retrotransposition events that occur in nature. Therefore, the
      DT40 cell system established here provides a powerful tool for the elucidation of
      LINE retrotransposition pathways, the host factors involved, and their roles.

PMID- 17434693
TI  - Complete mitochondrial genome of the bullhead torrent catfish, Liobagrus obesus
      (Siluriformes, Amblycipididae): Genome description and phylogenetic
      considerations inferred from the Cyt b and 16S rRNA genes.
AB  - Mitochondrial DNA (mtDNA) from the bullhead torrent catfish, Liobagrus obesus,
      was isolated by long-polymerase chain reaction (Long-PCR) with universal primers
      and was fully sequenced by primer working using flanking sequences. The complete
      mtDNA from L. obesus was 16,531 bp in length and contained 13 protein-coding
      genes, 2 rRNA genes, 22 tRNA genes, and a control region, demonstrating a
      structure very similar to that of other bony fish. An analysis of the protein
      coding genes revealed a statistically substantiated bias in (T+C): (A+G) content,
      supporting earlier findings regarding this peculiarity. As indicated by a chi
      square test, the observed scores for pyrimidine and purine content were different
      from those expected assuming a 50:50 ratio: chi(2)=41.63, d.f.=5, p<0.000001 for
      three categories, including the 1st, 2nd, and 3rd codon positions. Further, there
      was a difference in nucleotide content between ND6 and the other 12 protein
      coding genes in L. obesus. The values of p-distances, as summarized for different
      scales of evolutionary history at the Cyt b gene, revealed a clear pattern of
      increased nucleotide diversity at four levels: (1) intraspecies, (2) intragenus,
      (3) intrafamily, and (4) intraorder. Scores of average p-distances of the four
      categories in catfish were (1) 1.59+/-0.54%, (2) 5.28+/-1.72% (3) 16.37+/-1.26%,
      and (4) 19.81+/-0.14%, respectively. These data support the hypothesis that
      speciation in the order Siluriformes, in most cases, follows a geographic mode
      through the accumulation of a numerous small genetic changes over a long time
      period. A phylogenetic tree for the bullhead torrent catfish and several other
      fish species belonging to the order Siluriformes was developed on the basis of
      respective Cyt b sequences (1138 bp); the analysis revealed a monophyletic origin
      for the five examined families. A species-specific clustering of sequences from
      single species was obtained, supporting additionally basic phylogenetic
      information for the catfish and the barcoding suitability of Cyt b sequence data.
      Lastly, one of the well-supported properties of our phylogenetic tree (99%
      repetition level in our analysis) was the monophyletic placement of all catfish
      (order Siluriformes) among other ray-finned fish of the class Actinopterigii.
      Also discussed herein are the aspects of phylogeny based on the 16S rRNA gene.

PMID- 17434694
TI  - Maternal dietary omega fatty acid intake and auditory brainstem-evoked potentials
      in Mexican infants born at term: cluster analysis.
AB  - OBJECTIVE: To identify biological and socioeconomic factors associated with the
      neurological development of Mexican infants born at term, as measured by
      brainstem auditory-evoked potentials (BAEPs). SUBJECTS AND METHODS: We conducted
      a cohort study among 76 women with low risk pregnancies recruited in their third
      trimester of pregnancy and followed their infants until 12 months of age. BAEP
      tests were conducted on the infants before 3 months of age during physiologic
      sleep, using 100 msec bipolar clicks. Maternal dietary intake was evaluated by
      food frequency questionnaire. Two BAEP groups (short latency, long latency) were
      identified by cluster analysis. The association between BAEP group and maternal
      PUFAs was estimated using logistic regression models adjusted for socioeconomic
      and biological factors. RESULTS: Short latency BAEPs were associated with a
      maternal diet rich in arachidonic acid (OR=3.63, 95% CI 1.23-10.67) after
      adjusting for age (in days) sex, head circumference and gestational age but was
      not significantly associated to a maternal diet rich in docosahexaenoic acid
      (DHA). CONCLUSIONS: Our results suggest the importance of arachidonic acid intake
      during pregnancy for short latency BAEPs and adequate fetal myelination.

PMID- 17434695
TI  - Changes to the meiotic spindle and zona pellucida of mature mouse oocytes
      following different cryopreservation methods.
AB  - This study is to investigate the change of morphology of the meiotic spindle and
      the extent of zona hardening relating to the morphological survival and
      developmental competence of thawed oocytes. Four- to 8-week-old female mice
      (C57BL/6) primed with an intraperitoneal injection of pregnant mare's serum
      gonadotropin and human chorionic gonadotropin. Cryopreserved oocytes using two
      protocols: vitrificaton using ethylene glycol (EG) and slow freezing using
      propanediol (PROH). The freezing oocytes were thawed and were fertilized and
      subsequently cultured in vitro. Spindle/chromosome imagery, dissolution of zona
      pellucida, and post-thawing survival and development were comparable between two
      groups. The vitrification cryopreservation method proved to be better than the
      slow-freezing protocol when comparing the frequency of normal-shaped spindle
      development post-thawing. The difference in the time required for the dissolution
      of the zona pellucida under treatment of pronase that was determined to exist
      between the two cryopreservation methods was statistically significant (P<0.005).
      The survival rate of post-thawed mature oocytes was significantly greater for the
      vitrification group than it was for the slow-freezing cryopreservation group
      (P=0.005). The vitrification cryopreservation of mature murine oocytes would
      appear to be more satisfactory than the slow controlled-rate freezing method as
      regards the post-thawing oocyte survival and also the incidence of the normal
      spindle apparatus in the ooplasm.

PMID- 17434696
TI  - Auditory evoked field at threshold.
AB  - Auditory evoked responses are widely used for estimating electrophysiological
      thresholds, but the relationships to psychophysical thresholds are not
      necessarily straightforward. Among the aspects that are not well understood is
      the near-threshold intensity dependence of the evoked response. Here, we
      investigated wave N100m of the auditory evoked field. The stimulus was a 1-kHz
      tone with an effective duration of about 110 ms. Up to 10 dB above the
      psychophysical threshold, the level was varied in steps of 2dB; further
      measurements were done at 15, 20, 30, and 40 dB SL. Lower levels were presented
      with higher probability, to partially compensate for the expected signal-to-noise
      ratio reduction with decreasing level. The latency of the N100m could be
      characterized as a transmission delay and an integration time. The level
      dependence of the latter was consistent with the assumption of an almost
      perfectly operating sound-pressure integrator. The N100m amplitude increased
      roughly linearly with the level in dB (thus, as a logarithmic function of
      intensity), showing signs of saturation at higher levels.

PMID- 17434697
TI  - [Lyme borreliosis: follow up criteria after antibiotherapy?].
AB  - The post therapeutic follow-up of Lyme borreliosis is managed according to
      clinical and serological data. The evolution of antibody rates is such that it
      doesn't constitute the best element to rely on for follow-up. Indeed, after a
      sometimes transitory increase of this rate during or after antibiotherapy, the
      decrease is very slow, sometimes several months, and often incomplete. The follow
      up should thus be made according to clinical symptoms and their resolution.
      Resolution of some but not all symptoms must lead to discussing two options. The
      first is that of administrating a complementary antibiotherapy with a different
      mode of action than the first antibiotic used. The second is that this may be due
      to recontamination, especially in highly endemic zones, given that antibodies
      present have no protecting effect. In this case, a new antibiotherapy must of
      course be initiated.

PMID- 17434698
TI  - [Cutaneous drug reactions induced by glycopeptides].
AB  - Glycopeptides are a class of antibiotics used with a rising frequency because of
      the increasing number of infections due to Methicillin-resistant staphylococci.
      The dermatological adverse effect of vancomycin are well-known: "red man
      syndrome", maculopapular exanthema, etc., with some distinctive features such as
      Ig A linear dermatosis. Drug eruptions are less common but not insignificant when
      using teicoplanin, a more recent molecule. A given glycopeptide cannot be
      considered as an alternative for every patient "allergic" to another, because of
      cases of cross-reaction and the morbi-mortality of some cutaneous drug reactions.
      This emphasizes the importance to recognize early clinical signs. In this
      article, we review the various dermatological adverse drug reactions induced by
      glycopeptides, and suggest a possible management to clinicians who could be
      confronted with this problem.

PMID- 17434699
TI  - [Scientific basis for prevention].
AB  - Lyme Borreliosis is the most common tick-transmitted disease in North America and
      Europe. Borrelia burgdorferi sensu lato causes Lyme disease and is transmitted by
      a tick belonging to Ixodes genus. The risk of tick-borne infection depends on the
      ecology of ticks. The risk of human infection depends on the density of the tick
      population and its infection rate. The aim of this manuscript is to review the
      ecology of Ixodes ricinus the main vector of Lyme disease in Western Europe, the
      reservoir hosts, and studies on locations of Ixodes and Borrelia in France.
      Ixodes ricinus is widely distributed over the French territory except in
      Mediterranean areas and land above than 1,500 m.

PMID- 17434700
TI  - [Should presumptive meningoencephalitis treatment in adults be active against
      Mycoplasma pneumoniae?].
AB  - INTRODUCTION: Meningoencephalitis is the most common central nervous system
      complication caused by Mycoplasma pneumoniae. Its frequency is probably
      underestimated. OBJECTIVE: The study's aim was to determine the retrospectively
      incidence of M. pneumoniae meningoencephalitis among other cases of encephalitis
      diagnosed in infectiology, neurology and ICU at the Clermont-Ferrand University
      hospital in 2004 and 2005. DESIGN: A case of meningoencephalitis was defined by
      encephalopathy (altered level of consciousness and/or change in personality),
      with one or more of the following symptoms: fever, seizure, focal neurological
      findings, meningitis, electroencephalography or neuroimaging findings consistent
      with encephalitis. Tumor and hematoma diagnosed by scan were excluded. M.
      pneumoniae was considered as a possible cause when patients had positive
      serological test (IgM Elisa) and/or positive PCR results for the CSF. RESULTS:
      Four (8.3%) patients among 48 cases of encephalitis could have been caused by M.
      pneumoniae. All except one convulsed initially. Pneumopathy was found in two
      patients. All received a specific treatment later. Antibiotics seemed to
      influence evolution in only two patients. These 4 cases appeared during an
      epidemic between November 2004 and August 2005: 48 hospitalized adults had
      positive serological test for M. pneumoniae in 2005 and 15 in 2004, whereas the
      number of tests was the same in 2004 and in 2005. CONCLUSIONS: M. pneumoniae
      should be investigated as a cause of meningoencephalitis if initial tests are
      negative, if patients have respiratory symptoms and in case of epidemic.
      Presumptive treatment of meningoencephalitis should include an antibiotic active
      against M. pneumoniae.

PMID- 17434701
TI  - [Hydatid cyst of the posterior fossa].
AB  - Hydatidosis is an endemic affection in Tunisia. Cerebral echinococcosis is a
      relatively rare entity accounting for only 1-2% of all hydatid cysts in humans.
      Extradural hydatid cyst of the posterior fossa is a very uncommon site for the
      disease. We report the case of a four-year-old child admitted for high
      intracranial pressure. Brain CT scan showed an extradural posterior fossa cyst
      without enhancement after contrast medium injection. Operative finding revealed a
      hydatid cyst. The histological examination of the tissue sample confirmed the
      diagnosis. The patient was given albendazole post operatively. She feels well six
      months later.

PMID- 17434702
TI  - [Incidence of infections dues to Escherichia coli strains producing extended
      spectrum betalactamase, in the Zou/Collines Hospital Centre (CHDZ/C) in Benin].
AB  - OBJECTIVES: Over a 6-month period, extended-spectrum betalactamase (ESBL)
      producing isolates of Escherichia coli (EC) were collected from in-patients and
      their environment at the Zou-Collines Hospital Centre (CHDZ/C) in Benin. The aim
      of this study was to determine the incidence of ESBL and to describe their
      phenotypic susceptibility to antibiotics in a secondary hospital (500 beds) in
      Benin. METHODS: From 15 May to 15 November 2005, clinical informations and
      samples were collected from patients suspected to have nosocomial infections. The
      isolates were identified, tested for antimicrobial susceptibility and analysed
      for the presence of ESBL genes blaTEM and blaSHV by PCR. RESULTS: One hundred
      ninety-seven enterobacteria were isolated from the clinical samples of 342
      patients, these isolates included 143 EC and 32/143 (22%) of these isolates
      produced ESBL. Forty-six EC were isolated from the environment and 7 (15%) of
      them produced ESBL. Except for Imipenem for which the difference was not
      significant, the isolates producing ESBL were more resistant to the other
      antibiotics (especially to third generation cephalosporins: Ceftriaxone,
      Cefotaxime, Ceftazidime (P<0.00001)) than non-ESBL producing isolates. Both ESBL
      genes blaSHV and blaTEM were identified in the EC ESBL strains from patient and
      from the environment. CONCLUSION: This study shows the presence of ESBL genes
      among EC in various wards of the CHDZ/C hospital proving that there is a need to
      implement a strict hospital infection control program and a regular surveillance
      of resistance to antimicrobial agents.

PMID- 17434703
TI  - The Organizational Readiness for Change scale in adolescent programs: Criterion
      validity.
AB  - This study examined the convergent validity and concurrent validity of the
      Organizational Readiness for Change (ORC; Lehman WEK, Greener JM, Simpson DD,
      2002. Assessing organizational readiness for change. Journal of Substance Abuse
      Treatment. 22 197-210) scale among practitioners who treat adolescents. Within
      the context of a larger study, we administered the ORC scale and measures of
      practitioner attitudes toward evidence-based practices as well as treatment
      manuals to a heterogeneous sample of 543 community-based therapists in the state
      mental health and substance abuse treatment sectors. Using a contextual random
      effects regression model, the association between ORC scale domains and measures
      of practitioner characteristics and attitudes were examined at both therapist and
      agency levels. The results support the convergent validity and concurrent
      validity of several domains. Namely, the domains focusing on motivational
      readiness and training needs were associated with higher appeal and openness to
      innovations. Those on program resources and climate were less related, however.
      Our discussion focuses on the utility of the ORC scale in helping evaluate the
      needs of programs considering the adoption of evidence-based practices.

PMID- 17434704
TI  - Moving innovations into treatment: A stage-based approach to program change.
AB  - Treatment programs are expected to change their clients. To adopt evidence-based
      practices to improve their therapeutic effectiveness in dealing with drug-related
      problems of clients, they also are expected to change themselves. The process of
      innovation adoption and implementation is the focus of studies included in this
      special journal issue. Collectively, this volume examines staff perceptions of
      program needs, organizational readiness for change (based on pressures,
      resources, staff attributes, and organizational climate), quality of workshop
      training, subsequent utilization of training materials, and client self-report of
      treatment engagement. Approximately 800 treatment programs nationwide contributed
      data for these studies. A standardized assessment of organizational functioning
      captured attributes that describe environments, settings, and staffs, and the
      findings are interpreted in the context of a stage-based approach to program
      changes. A conceptual model is used to help organize and summarize longitudinal
      results within the organizational context and according to implementation
      influences related to qualities of the innovations.

PMID- 17434705
TI  - Assessing program needs and planning change.
AB  - Assessments of treatment staff training needs, preferences, and barriers can help
      guide and improve training activities and transfer evidence-based technologies
      into clinical practice. The Texas Christian University (TCU) Program Training
      Needs (PTN) assessment consists of 54 items organized into seven domains: Program
      Facilities and Climate, Program Computer Resources, Staff Training Needs,
      Preferences for Training Content, Preferences for Training Strategy, Training
      Barriers, and Satisfaction With Training. Data collected from 589 counselors
      representing 194 treatment programs showed that the PTN was psychometrically
      sound and predictably associated with results from a more comprehensive
      assessment of organizational functioning. Importantly, fewer barriers to training
      and greater staff satisfaction with training were reported for programs with
      higher levels of organizational functioning. In addition to representing an
      efficient source of staff's perceptions about organizational operations and
      needs, the PTN empowers staff with a "voice" through which they can contribute to
      strategic planning and priority setting for organizational actions.

PMID- 17434706
TI  - Counselor perceptions of organizational factors and innovations training
      experiences.
AB  - Because work environment is central to understanding job performance, drug
      counselor perceptions of their programs and their skills were examined in
      relation to their attitudes about innovations training and its utilization.
      Latent profile analysis of measures on organizational climate and staff
      attributes for 1047 counselors from 345 programs defined three categories of
      counselors-labeled as isolated, integrated, and exceptional. All had generally
      positive views of their professional skills, although the isolated group scored
      lower on scales representing professional growth and influence on peers. They
      were less positive about the "climate" of programs in which they worked and were
      higher on stress. Program resources predicted the counselor groups, with the
      isolated having more limited resources. Counselor categorizations also differed
      in terms of workshop training experiences, with the isolated group of counselors
      reporting significantly less exposure, satisfaction, and program-wide use of
      workshop training.

PMID- 17434707
TI  - Counselor assessments of training and adoption barriers.
AB  - The prevailing emphasis on adopting evidence-based practices suggests that more
      focused training evaluations that capture factors in clinician decisions to use
      new techniques are needed. This includes relationships between postconference
      evaluations and subsequent adoption of training materials. We therefore collected
      training assessments at two time points from substance abuse treatment counselors
      who attended a training on dual diagnosis and another on therapeutic alliance as
      part of a state-sponsored conference. Customized evaluations were collected to
      assess counselor perceptions of training quality, relevance, and resources in
      relation to its use during the 6 months after the conference. Higher ratings for
      relevance of training concepts and materials to service the needs of clients,
      desire to have additional training, and level of program support were related to
      greater trial use during the follow-up period. Primary resource-related and
      procedural barriers cited by the counselors included lack of time and redundancy
      with existing practices.

PMID- 17434708
TI  - Organizational Readiness for Change and opinions toward treatment innovations.
AB  - Program administrators and staff in treatment programs participating in the
      National Drug Abuse Treatment Clinical Trials Network completed surveys to
      characterize participating programs and practitioners. A two-level random-effects
      regression model assessed the influence of Organizational Readiness for Change
      (ORC) and organizational attributes on opinions toward the use of four evidence
      based practices (manualized treatments, medication, integrated mental health
      services, and motivational incentives) and practices with less empirical support
      (confrontation and noncompliance discharge). The ORC scales suggested greater
      support for evidence-based practices in programs where staff perceived more
      program need for improvement, better Internet access, higher levels of peer
      influence, more opportunities for professional growth, a stronger sense of
      organizational mission, and more organizational stress. Support for confrontation
      and noncompliance discharge, in contrast, was strong when staff saw less
      opportunity for professional growth, weaker peer influence, less Internet access,
      and perceived less organizational stress. The analysis provides evidence of the
      ORC's utility in assessing agency strengths and needs during the implementation
      of evidence-based practices.

PMID- 17434709
TI  - Program structure, staff perceptions, and client engagement in treatment.
AB  - A key goal of drug abuse treatment providers is getting their clients to engage
      and participate in therapeutic activities as a first step toward deriving longer
      term benefits. Much research had focused on personal characteristics that relate
      to client engagement; program characteristics have received less attention. This
      study explored client and program differences in engagement ratings using data
      from a nationwide set of 94 outpatient drug-free treatment programs in a
      hierarchical linear model analysis. The results show that elements of program
      context, including structural features (e.g., smaller size and Joint Commission
      on the Accreditation of Healthcare Organizations/Commission on Accreditation of
      Rehabilitation Facilities accreditation) and staff's perceptions of personal
      efficacy, organizational climate, and communal workplace practices, relate to
      better overall client engagement. These findings add further evidence that
      treatment providers should also address the workplace environment for staff as
      part of quality improvement efforts.

PMID- 17434710
TI  - Characterization of the P373L E-cadherin germline missense mutation and
      implication for clinical management.
AB  - AIM: Hereditary diffuse gastric cancer (HDGC) is a cancer susceptibility syndrome
      caused by E-cadherin germline mutations. One-third of these mutations are of the
      missense type, representing a burden in genetic counselling. A new germline
      missense mutation (P373L) was recently identified in a HDGC Italian family. The
      present work aimed at addressing the disease-causative nature of the P373L
      mutant. METHODS: Assessment of the P373L mutation effect was based on cell
      aggregation and invasion assays. LOH analysis at the E-cadherin locus, search for
      somatic E-cadherin mutations and for promoter hypermethylation were performed to
      identify the mechanism of inactivation of the E-cadherin wild-type allele in the
      tumour. RESULTS: In vitro the P373L germline mutation impaired the E-cadherin
      functions. E-cadherin promoter hypermethylation was observed in the tumour of the
      P373L mutation carrier. CONCLUSION: We conclude that the combination of clinical,
      in vitro and molecular genetic data is helpful for establishing an accurate
      analysis of HDGC-associated CDH1 germline missense mutations and subsequently for
      appropriate clinical management of asymptomatic mutation carriers.

PMID- 17434711
TI  - Radiofrequency ablation after transarterial embolization as therapy for patients
      with unresectable hepatocellular carcinoma.
AB  - PURPOSE: To evaluate the usefulness of transcatheter arterial embolization (TAE)
      followed by radiofrequency ablation (RFA) as combined treatment for unresectable
      hepatocellular carcinoma (HCC). PATIENTS AND METHODS: Thirty-six consecutive
      patients (cirrhosis, Child-Pugh class A or B) with solitary or oligonodular HCC
      were treated (41 lesions; mean size, 58.9 mm; range, 30-120 mm). RFA was
      performed after one TAE treatment. Local efficacy was evaluated with multiphasic
      computed tomography (CT) performed an average of two months after RFA and once
      during later follow-up. RESULTS: The mean follow-up period was 16 months (range,
      2-45 months). Technical success (namely, complete tumor devascularization during
      the arterial phase) was achieved for 59% of lesions at the first CT evaluation
      and for 46% at the second evaluation. Among prognostic factors included in the
      analysis, only lesion diameter (< 50 mm versus > or = 50 mm) was statistically
      significant in terms of predicting local success (Fisher's exact test: 85% versus
      43% at first CT, p<0.01; 70% versus 36% during follow-up, p=0.05). There were no
      major periprocedural complications. Kaplan-Meier analysis showed survival rates
      of 84% at 12 months and 57% at 24 months. CONCLUSIONS: Combined therapy--TAE then
      RFA--for unresectable HCC lesions in patients with cirrhosis produces a
      relatively high complete local response rate compared with TAE or RFA alone. Our
      results, considered with those from other case series, may help design
      prospective, randomized clinical trials to test combination therapy versus single
      modality therapy in terms of risks and benefits.

PMID- 17434712
TI  - [Hierarchical strategy for treating elevated intracranial pressure in severe
      traumatic brain injury].
AB  - The objective of the treatment of intracranial hypertension is to decrease
      intracranial pressure (ICP) while maintaining cerebral blood flow (CBF). Despite
      numerous treatments, none of them associates total efficiency and security.
      Systemic secondary cerebral injuries, which are responsible for cerebral
      ischemia, lead us to administer non specific treatments in order to optimize CBF
      and cerebral oxygenation. Thus, the goals are: 1) to maintain cerebral perfusion
      pressure> or =70 mmHg; 2) to control metabolic status by preventing
      hyperglycaemia, anaemia and hyperthermia; 3) to maintain normoxia and normocapnia
      (hypercapnia increases ICP and hypocapnia decreases CBF). Beside the
      neurosurgical evacuation of extra- and intraparenchymatous haematomas,
      osmotherapy and cerebrospinal fluid (CSF) evacuation are the two specific
      treatments of intracranial hypertension. Osmotherapy consists in an
      administration of a hypertonic solution which induces a decrease in cerebral
      water and finally in ICP. Mannitol (20%), which is the reference, associates
      osmotic and rheologic effects, and decreases CSF production too. Recent data
      conduct us to administer larger doses, between 0.7 and 1 g/kg in 15 minutes.
      Hypertonic saline solution associates osmotic effects and plasma volume loading.
      Thus, this solution is particularly appropriate in severe head injury with
      arterial hypotension. CBF evacuation decreases rapidly ICP without any major side
      effect. Until now, there is no proof of a superior efficiency of a treatment for
      intracranial hypertension compared to another. Considering their mechanism of
      action, all of them are efficient but potentially dangerous too. Indeed, the
      choice between treatments depends on data which are issued from the multimodal
      monitoring. General non specific treatments are always necessary. Specific
      treatments are indicated if ICP is above 20-25 mmHg. Maintaining cerebral
      perfusion pressure represents the first therapeutic goal. If intracranial
      hypertension persists, evacuation of CBF or osmotherapy may be advocated. In case
      of refractory intracranial hypertension, it may be useful to deepen
      neurosedation. Controlled hypocapnia and barbiturates remain a third line therapy
      providing to monitor and maintain an appropriate CBF and cerebral oxygenation.
      Controlled hypothermia and decompressive craniectomy must be individually
      discussed.

PMID- 17434713
TI  - Molecular and supra-molecular structure related differences in toxicity and
      granulomatogenic activity of mycobacterial cord factor in mice.
AB  - To establish the structure biological activity relationship of cord factor
      (trehalose 6,6'-dimycolate, TDM), we compared the molecular or supra-molecular
      structure of TDM micelles with toxicity, thymic atrophy and granulomatogenicity
      in lungs and spleen of BALB/c mice. According to the difference in the mycolyl
      subclass composition, TDM was divided into two groups, one possessing alpha-,
      methoxy- and keto-mycolates in M. tuberculosis H37Rv, M. bovis BCG and M.
      kansasii (group A) and the other having alpha-, keto- and wax ester-mycolates in
      M. avium serotype 4, M. phlei and M. flavescens (group B), although mycolic acid
      molecular species composition differed in each group considerably. Supra
      molecular structure of TDM micelle differed species to species substantially and
      the micelle size of TDM from M. bovis BCG Connaught was the largest. The highest
      toxicity was shown with TDM from M. tuberculosis H37Rv which possessed the
      highest amount of alpha- (47.3%) and methoxy-mycolates (40.8%), while TDM from M.
      phlei having the low amount of alpha-mycolate (11.6%) showed almost no toxicity
      with the given doses. The thymic atrophy was observed with TDM from group A, but
      not with TDM from group B. On the other hand, TDM from group B showed massive
      lung granulomatogenic activity based on the histological observations and organ
      indices. Taken together, group A TDM showed a wide variety of micelle sizes and
      specific surface areas, high to low toxicity and marked to moderate
      granulomatogenicity, while group B TDM showed smaller sizes of micelles and
      larger specific surface areas, lower toxicity but higher granulomatogenicity in
      lungs. Existence of higher amount of longer chain alpha-mycolates in TDM appeared
      to be essential for high toxicity and thymic apoptotic activity, whereas TDM
      possessing wax ester-mycolate with smaller sized micelles seemed to be less
      toxic, but more granulomatogenic in lungs in mice. Thus, the mycolic acid
      subclass and molecular species composition of TDM affect critically the micelle
      forms, toxicity and granulomatogenicity in mice, while the relative abundances
      and carbon chain length of alpha-mycolate affected the toxicity in mice.

PMID- 17434714
TI  - Immunostimulatory antibodies: challenging the drug testing paradigm.
AB  - The recently failed first-in-man clinical trial of TGN1412 raises concerns about
      whether the existing drug testing paradigm is suited to the safety assessment of
      drugs based on immunostimulatory antibodies that have complex and novel
      mechanisms of action. In particular, there is a need to consider whether animal
      studies are relevant and, if so, how the resulting information can be used to
      best inform clinical studies. The preclinical testing of TGN1412 is considered in
      relation to the selection of a suitable test species, deficiencies in an
      understanding of the similarities and differences between human and other primate
      immune functioning and species extrapolation. It is concluded that more emphasis
      should be placed on the development and use of in vitro and computational methods
      to identify potentially important species differences in the activity of
      immunostimulatory antibodies. Such approaches are useful with regards to species
      extrapolation, mechanistic studies and the design of both preclinical tests in
      animals and clinical studies in humans.

PMID- 17434715
TI  - Validation of the French version of the BACS (the brief assessment of cognition
      in schizophrenia) among 50 French schizophrenic patients.
AB  - Schizophrenic patients demonstrate impairments in several key dimensions of
      cognition. These impairments are correlated with important aspects of functional
      outcome. While assessment of these cognition disorders is increasingly becoming a
      part of clinical and research practice in schizophrenia, there is no standard and
      easily administered test battery. The BACS (Brief Assessment of Cognition in
      Schizophrenia) has been validated in English language [Keefe RSE, Golberg TE,
      Harvey PD, Gold JM, Poe MP, Coughenour L. The Brief Assessment of Cognition in
      Schizophrenia: reliability, sensibility, and comparison with a standard
      neurocognitive battery. Schizophr. Res 2004;68:283-97], and was found to be as
      sensitive to cognitive dysfunction as a standard battery of tests, with the
      advantage of requiring less than 35 min to complete. We developed a French
      adaptation of the BACS and this study tested its ease of administration and
      concurrent validity. Correlation analyses between the BACS (version A) and a
      standard battery were performed. A sample of 50 stable schizophrenic patients
      received the French Version A of the BACS in a first session, and in a second
      session a standard battery. All the patients completed each of the subtests of
      the French BACS . The mean duration of completion for the BACS French version was
      36 min (S.D.=5.56). A correlation analysis between the BACS (version A) global
      score and the standard battery global score showed a significant result (r=0.81,
      p<0.0001). The correlation analysis between the BACS (version A) sub-scores and
      the standard battery sub-scores showed significant results for verbal memory,
      working memory, verbal fluency, attention and speed of information processing and
      executive functions (p<0.001) and for motor speed (p<0.05). The French Version of
      the BACS is easier to use in French schizophrenic patients compared to a standard
      battery (administration shorter and completion rate better) and its good
      psychometric properties suggest that the French Version of the BACS may be a
      useful tool for assessing cognition in schizophrenic patients with French as
      their primary language.

PMID- 17434716
TI  - Chronic amphetamine treatment reduces NGF and BDNF in the rat brain.
AB  - Amphetamines (methamphetamine and d-amphetamine) are dopaminergic and
      noradrenergic agonists and are highly addictive drugs with neurotoxic effect on
      the brain. In human subjects, it has also been observed that amphetamine causes
      psychosis resembling positive symptoms of schizophrenia. Neurotrophins are
      molecules involved in neuronal survival and plasticity and protect neurons
      against (BDNF) are the most abundant neurotrophins in the central nervous system
      (CNS) and are important survival factors for cholinergic and dopaminergic
      neurons. Interestingly, it has been proposed that deficits in the production or
      utilization of neurotrophins participate in the pathogenesis of schizophrenia. In
      this study in order to investigate the mechanism of amphetamine-induced
      neurotoxicity and further elucidate the role of neurotrophins in the pathogenesis
      of schizophrenia we administered intraperitoneally d-amphetamine for 8 days to
      rats and measured the levels of neurotrophins NGF and BDNF in selected brain
      regions by ELISA. Amphetamine reduced NGF levels in the hippocampus, occipital
      cortex and hypothalamus and of BDNF in the occipital cortex and hypothalamus.
      Thus the present data indicate that chronic amphetamine can reduce the levels of
      NGF and BDNF in selected brain regions. This reduction may account for some of
      the effects of amphetamine in the CNS neurons and provides evidences for the role
      of neurotrophins in schizophrenia.

PMID- 17434717
TI  - [Surveillance of intussusception in France].

PMID- 17434718
TI  - [Acute idiopathic thrombocytopenic purpura: what's new in 2007?].

PMID- 17434719
TI  - Adjuvant chemoradiation for gastric cancer: experience in the Chinese population.
AB  - AIMS: The role of adjuvant chemoradiation for gastric cancer after curative R0
      gastrectomy was first established by the US Intergroup 0116 study. Although
      confirmatory studies are in progress, few data are available regarding its
      application to the Chinese population. We describe our radiotherapy technique and
      report the treatment results in Hong Kong. MATERIALS AND METHODS: This was a
      single centre retrospective study on 63 Chinese patients who underwent adjuvant
      chemoradiation for gastric adenocarcinoma between June 2000 and December 2004.
      The treatment protocol was based on that of the Intergroup study. Computed
      tomography planned anteroposterior opposing field arrangement and treatment under
      breath hold at deep inspiration position were adopted. RESULTS: In total, 63
      patients, mean age 50 years, with gastric cancer stage IB to limited metastatic
      IV disease were analysed. The median follow-up time was 27.2 months. The relapse
      free survival and overall survival at 3 years were 50 and 54%, respectively. The
      recurrence pattern was dominated by distant failure and only one patient
      developed isolated locoregional recurrence. Of the 10 patients who had positive
      microscopic surgical margins after surgery, seven had recurred and died. On
      multivariate analysis, margin status was the only significant prognosticator for
      survival. Thirty per cent of patients experienced grade 3 or above acute toxicity
      (24% haematological, 14% gastrointestinal) and one patient died of neutropenic
      sepsis. There was one case of grade 3 late toxicity. CONCLUSIONS: The outcome
      after adjuvant chemoradiation for gastric cancer seemed to be favourable, with
      manageable toxicities, in the Chinese population. Locoregional failure was
      uncommon. Patients with microscopic surgical margin involvement had a very high
      failure rate despite adjuvant chemoradiation.

PMID- 17434720
TI  - An analysis of peroxisome proliferator-activated receptor gamma (PPAR-gamma 2)
      Pro12Ala polymorphism distribution and prevalence of type 2 diabetes mellitus
      (T2DM) in world populations in relation to dietary habits.
AB  - BACKGROUND AND AIM: The human peroxisome proliferator-activated receptor gamma
      (PPAR-gamma) is involved in lipid storage, glucose homeostasis and adipocyte
      differentiation. The Ala allele of the Pro12Ala polymorphism has been associated
      with a protective effect against T2DM. Ala allele frequencies are known for many
      populations, but data are absent for other interesting human groups. METHODS AND
      RESULTS: We examined samples from Ethiopia, Benin, Ecuador and Italy. In
      addition, we performed an analysis of the Pro12Ala polymorphism distribution in
      world populations, also in relation to T2DM prevalence and the diet lipid
      content. In the European populations, the Ala allele frequencies are distributed
      according to a latitudinal trend, with the highest in the northern and central
      European populations and the lowest in the Mediterranean populations. Considering
      the world populations, a significant inverse relationship between Ala frequency
      and T2DM prevalence was observed mainly in populations where energy from lipids
      exceeded 30% of the total energy intake. CONCLUSION: Northern Europe's cold
      climate has been hypothesised to have played a role in contributing to the
      present pattern. Moreover our analysis appears to confirm, at a population level,
      the protective effect of Ala allele against T2DM, already observed in case
      control studies, but only in populations with a diet rich in lipids.

PMID- 17434721
TI  - K12-biotinylated histone H4 marks heterochromatin in human lymphoblastoma cells.
AB  - Covalent modifications of histones play crucial roles in chromatin structure and
      genomic stability. Recently, we reported a novel modification of histones:
      biotinylation of lysine residues. Here we provide evidence that K12-biotinylated
      histone H4 (K12Bio H4) maps specifically to both heterochromatin (alpha satellite
      repeats in pericentromeric regions) and transcriptionally repressed chromatin
      (gamma-G globin and interleukin-2) in human lymphoblastoma cells. The abundance
      of K12Bio H4 in these regions was similar to that of K9-dimethylated histone H3,
      a known marker for heterochromatin. Likewise, K8-biotinylated histone H4 (K8Bio
      H4) mapped to heterochromatin, but the relative enrichment was smaller compared
      with K12Bio H4. Stimulation of interleukin-2 transcriptional activity with
      phorbol-12-myristate-13-acetate and phytohemagglutinin caused a rapid depletion
      of K12Bio H4 in the gene promoter. These data are consistent with a novel role
      for biotin in chromatin structure and transcriptional activity of genes.

PMID- 17434723
TI  - Consumption of a moderately Zn-deficient and Zn-supplemented diet affects soluble
      protein expression in rat soleus muscle.
AB  - Zinc deficiency negatively affects muscle function, but there are limited
      biochemical data identifying the cause of this reduction in function. The
      objective of the present study was to identify soluble proteins in rat soleus
      muscle that were responsive to different levels of dietary zinc. Rats (n=21) were
      fed diets containing three concentrations of zinc: 5, 30 and 200 ppm for 42 days.
      There was no difference in body weights of the rats consuming the 5-ppm zinc diet
      compared to the rats consuming the 30- or 200-ppm zinc diets; however, bone zinc
      levels were significantly decreased in the 5-ppm dietary zinc group. Individual
      soluble protein fractions were isolated from these muscles and the samples were
      prepared for two-dimensional polyacrylamide gel electrophoresis. The expression
      levels of four proteins were significantly depressed by dietary Zn depletion and
      supplementation, S-glutathiolated carbonic anhydrase, myosin light polypeptide 3,
      heat shock protein 20 and heart fatty acid binding protein. This is the first
      report that indicates that both Zn depletion and supplementation result in
      protein expression profiles that may negatively affect skeletal muscle function.
      These results indicate that there are specific signaling pathways that require
      proper Zn nutriture for maintaining optimal muscle function and suggest that the
      consumption of pharmacologic doses of Zn may be detrimental to muscle function.

PMID- 17434722
TI  - Estrogen receptor activation and estrogen-regulated gene expression are
      unaffected by methylseleninic acid in LNCaP prostate cancer cells.
AB  - Prostate cancer is the most frequently diagnosed cancer and a leading cause of
      cancer deaths in American men. High dietary intake and status of the essential
      trace element selenium (Se) have been consistently correlated with reduced risk
      for prostate cancer. One molecular mechanism by which Se may reduce prostate
      cancer risk is by catalyzing disulfide bond formation or, otherwise, complexing
      with reactive sulfhydryl groups in transcription factors, thus altering their
      binding to DNA and regulation of gene expression. Estrogen plays a role in the
      etiology of prostate cancer. Estrogen receptors contain cysteines in zinc fingers
      that are susceptible to oxidation and internal disulfide bond formation, which
      can prevent DNA binding. We hypothesized that Se alteration of estrogen receptor
      (ER) binding to DNA and estrogen-regulated gene expression may be one mechanism
      by which it exerts its chemopreventive effects. LNCaP human prostate cancer cells
      were treated with 0.05 mumol/L (control) or 5.0 mumol/L (high) Se as
      methylseleninic acid (MSA). Electrophoretic mobility shift assays showed that
      binding of ER-beta to the estrogen response element was a nonsignificant 14%
      lower in cells treated with high MSA. Run-on transcription assays showed no
      significant changes in transcription rates for estrogen-regulated genes, and
      steady-state mRNA levels for those genes, assayed by reverse transcription
      polymerase chair reaction, were likewise unaffected by MSA. These results suggest
      that the well-documented chemopreventive effects of Se against prostate cancer
      may be mediated by mechanisms other than inhibition by monomethylated Se
      compounds of ER-beta activation or estrogen-regulated gene expression.

PMID- 17434724
TI  - n-3 PUFA attenuate lipopolysaccharide-induced down-regulation of toll-like
      receptor 4 expression in porcine adipose tissue but does not alter the expression
      of other immune modulators.
AB  - The objective of this study was to test the hypothesis that the inflammatory
      response to lipopolysaccharide (LPS) in vivo is accompanied by down-regulation of
      toll-like receptor (TLR) 4 in adipose tissue, and a source of protected n-3
      polyunsaturated fatty acid (PUFA) attenuates this response. Seventy-two castrated
      male pigs were individually fed either a control (CONT) diet, or the CONT diet
      containing 1.87% (LF) or 7.50% (HF) protected n-3 PUFA on a weight basis for 7
      weeks. Adipose and muscle tissue biopsy samples were taken at Weeks 1, 2, 3, 4
      and 7 to assess gene expression and/or confirm tissue enrichment with
      eicosapentaenoic acid and docosahexaenoic acid and reflected the n-3 PUFA
      contained in the diet. The LPS challenge was performed at week 7 and consisted of
      sequential injections of 10 and 2.5 mug LPS per kilogram of body weight 23 h
      apart. The LPS challenge resulted in a marked down-regulation (P=.004) of TLR4 at
      the protein level in the adipose tissue of challenged vs. control pigs, but LF
      and HF clearly blocked this response at the mRNA level. Although LF and HF also
      attenuated (P<.001) the LPS-induced acute febrile response and lowered (P<.002)
      serum concentrations of tumour necrosis factor alpha. Cyclooxygenase 2 and 12
      lipoxygenase were readily expressed in porcine adipose tissue, but there was no
      effect of LF, HF or LPS on expression levels of these inflammatory mediators, or
      that of TNF and interleukin 6, at the conclusion of the challenge period. These
      findings indicate that adipose tissue responds to LPS administration in vivo by
      reducing TLR4 mRNA and protein abundance and that the anti-inflammatory effects
      of n-3 PUFA do not include down-regulation of TLR4 in adipose tissue.

PMID- 17434725
TI  - Physiological concentrations of butyrate favorably modulate genes of oxidative
      and metabolic stress in primary human colon cells.
AB  - Butyrate, a metabolite of gut flora-mediated fermentation of dietary fibre, was
      analysed for effects on expression of genes related to oxidative stress in
      primary human colon cells. An induction of detoxifying, antioxidative genes is
      expected to contribute to dietary chemoprevention. Cells were treated with
      butyrate (3.125-50 mM; 0.5-8 h), and kinetics of uptake and survival were
      measured. Gene expression was determined with a pathway-specific cDNA array after
      treating colon epithelium stripes with nontoxic doses of butyrate (10 mM, 12 h).
      Changes of hCOX-2, hSOD2 and hCAT expression were confirmed with real-time
      polymerase chain reaction (PCR) and by measuring catalase-enzyme activity.
      Primary colon cells consumed 1.5 and 0.5 mM butyrate after 4- and 12-h treatment,
      respectively. Cell viability was not changed by butyrate during 0.5-2-h
      treatment, whereas cell yields decreased after 1 h. Metabolic activity of
      remaining cells was either increased (4 h, 50 mM) or retained at 97% (8 h, 50
      mM). Expression of hCAT was enhanced, whereas hCOX-2 and hSOD2 were lowered
      according to both array and real-time PCR analysis. An enhanced catalase-enzyme
      activity was detected after 2 h butyrate treatment. Healthy nontransformed colon
      cells well tolerated butyrate (50 mM, 2 h), and lower concentrations (10 mM, 12
      h) modulated cyclooxygenase 2 (COX-2) and catalase genes. This points to a dual
      role of chemoprotection, since less COX-2 could reduce inflammatory processes,
      whereas more catalase improves detoxification of hydrogen peroxide (H(2)O(2)), a
      compound of oxidative stress. Changes of this type could reduce damaging effects
      by oxidants and protect cells from initiation.

PMID- 17434726
TI  - What life-cycle assessment does and does not do in assessments of waste
      management.
AB  - In assessments of the environmental impacts of waste management, life-cycle
      assessment (LCA) helps expanding the perspective beyond the waste management
      system. This is important, since the indirect environmental impacts caused by
      surrounding systems, such as energy and material production, often override the
      direct impacts of the waste management system itself. However, the applicability
      of LCA for waste management planning and policy-making is restricted by certain
      limitations, some of which are characteristics inherent to LCA methodology as
      such, and some of which are relevant specifically in the context of waste
      management. Several of them are relevant also for other types of systems
      analysis. We have identified and discussed such characteristics with regard to
      how they may restrict the applicability of LCA in the context of waste
      management. Efforts to improve LCA with regard to these aspects are also
      described. We also identify what other tools are available for investigating
      issues that cannot be adequately dealt with by traditional LCA models, and
      discuss whether LCA methodology should be expanded rather than complemented by
      other tools to increase its scope and applicability.

PMID- 17434727
TI  - Sulindac treatment in hereditary non-polyposis colorectal cancer.
AB  - Non-steroidal anti-inflammatory drugs, e.g. sulindac have been extensively
      studied for chemoprevention in familial adenomatous polyposis, but not in
      hereditary non-polyposis colorectal cancer (HNPCC). We evaluated these effects in
      HNPCC using surrogate end-points for cancer risk. In a randomised double-blind
      cross-over study, 22 subjects (9 female; age 30-66 years, mean 44), all
      ascertained or probable mutation carriers for HNPCC, were included. Sulindac 150
      mg b.i.d. and placebo were given for 4 weeks each, with 4 weeks in between, with
      biopsies taken from ascending, transverse and sigmoid colon and rectum by
      colonoscopy after both periods. Proliferation was determined by Ki-67 staining
      and apoptosis by staining of cytokeratin 18 cleavage products. Expression of
      cyclins B1, D3 and E and p21, p27, bax, bcl2 and cox-2 was studied
      immunohistochemically. Proliferation was higher during sulindac treatment than
      drug placebo treatment in ascending and transverse colon, but not in sigmoid and
      rectum. Apoptosis was not affected. Besides an increase in cyclin D3, no
      differences were found in expression of regulating proteins in the proximal
      colon. CONCLUSION: Sulindac induces an increase in epithelial cell proliferation
      in the proximal colon of subjects with HNPCC. Since colorectal cancer
      predominantly arises in the proximal colon in HNPCC, these results cast doubts on
      the potential chemopreventive effects of sulindac in HNPCC.

PMID- 17434728
TI  - Kinetics of sunflower oil methanolysis at low temperatures.
AB  - The kinetics of the sunflower oil methanolysis process was studied at lower
      temperatures (10-30 degrees C). The sigmoidal kinetics of the process was
      explained by the mass transfer controlled region in the initial heterogenous
      regime, followed by the chemical reaction controlled region in the pseudo
      homogenous regime. A simple kinetic model, which did not require complex
      computation of the kinetic constants, was used for simulation of the TG
      conversion and the FAME formation in the latter regime: the fast irreversible
      second-order reaction was followed by the slow reversible second-order reaction
      close to the completion of the methanolysis reaction. The mass transfer was
      related to the drop size of the dispersed (methanol) phase, which reduced rapidly
      with the progress of the methanolysis reaction. This was attributed to the
      formation of the emulsifying agents stabilizing the emulsion of methanol drops
      into the oil.

PMID- 17434729
TI  - Rhamnolipid production with indigenous Pseudomonas aeruginosa EM1 isolated from
      oil-contaminated site.
AB  - Rhamnolipid is one of the most effective and commonly used biosurfactant with
      wide industrial applications. Systematic strategies were applied to improve
      rhamnolipid (RL) production with a newly isolated indigenous strain Pseudomonas
      aeruginosa EM1 originating from an oil-contaminated site located in southern
      Taiwan. Seven carbon substrates and four nitrogen sources were examined for their
      effects on RL production. In addition, the effect of carbon to nitrogen (C/N)
      ratio on RL production was also studied. Single-factor experiments show that the
      most favorable carbon sources for RL production were glucose and glycerol (both
      at 40 g/L), giving a RL yield of 7.5 and 4.9 g/L, respectively. Meanwhile, sodium
      nitrate appeared to be the preferable nitrogen source, resulting in a RL
      production of 8.6g/L. Using NaNO(3) as the nitrogen source, an optimal C/N ratio
      of 26 and 52 was obtained for glucose- and glycerol-based culture, respectively.
      To further optimize the composition of fermentation medium, twenty experiments
      were designed by response surface methodology (RSM) to explore the favorable
      concentration of three critical components in the medium (i.e., glucose,
      glycerol, and NaNO(3)). The RSM analysis gave an optimal concentration of 30.5,
      18.1, and 4.9 g/L for glucose, glycerol, and NaNO(3), respectively, predicting a
      maximum RL yield of 12.6 g/L, which is 47% higher than the best yield (8.6 g/L)
      obtained from preliminary selection tests and single factor experiments (glucose
      and NaNO(3) as the carbon and nitrogen source). The NMR and mass spectrometry
      analysis show that the purified RL product contained L-rhamnosyl-beta
      hydroxydecanoyl-beta-hydroxydecanoate (RL1) and L-rhamnosyl L-rhamnosyl-beta
      hydroxydecanoyl-beta-hydroxydecanoate (RL2). Meanwhile, HPLC analysis indicates
      that the molar ratio of RL1 and RL2 in the purified rhamnolipid product was ca.
      1:1.

PMID- 17434730
TI  - Use of industrial wastewater from olive-oil extraction for biomass production of
      Scenedesmus obliquus.
AB  - The use of rinse water (RW) from two-phase centrifugation in the olive-oil
      extraction industry has been studied in relation to the production of the
      microalga Scenedesmus obliquus (CCAP 276/3A). The characterization of the
      wastewater indicates that it is N deficient. The highest value of maximum
      specific growth rate, 0.044 h(-1) was registered in the culture with 5% RW.
      However, biomass productivity proved greater in the culture with 100% RW. The
      specific growth rates were adjusted to a model of inhibition by substrate. The
      content in normalized chlorophyll diminished with the duration of the cultures,
      reaching a minimum CHL'(min) value, which showed an inhibition type similar to
      that of the specific growth rate. The yield in protein indicates that the
      cultures were limited by N to approximately 50% RW. The greater specific rate of
      protein synthesis during the exponential phase was 3.7 mg/gh to 50% RW. It was
      found that the composition of the lipid fraction of the biomass depended on the
      percentage of wastewater used as the nutrient medium, reaching the highest
      percentages of monounsaturated, polyunsaturated, and essential fatty acids in the
      culture with 100% RW.

PMID- 17434731
TI  - Naphthyl piperazines with dual activity as 5-HT1D antagonists and 5-HT reuptake
      inhibitors.
AB  - SAR around a known molecule with dual 5-HT(1D) antagonist and 5-HT(transporter)
      inhibitory activity has led to the discovery of molecules with improved dual
      activity and reduced cross-reactivity toward other aminergic receptors (5-HT(1B),
      alpha(1), and D(2)).

PMID- 17434732
TI  - Triazolopiperazine-amides as dipeptidyl peptidase IV inhibitors: close analogs of
      JANUVIA (sitagliptin phosphate).
AB  - A series of beta-aminoamides bearing triazolopiperazines has been prepared and
      evaluated as potent, selective, orally active dipeptidyl peptidase IV (DPP-4)
      inhibitors. Efforts at optimization of the beta-aminoamide series, which
      ultimately led to the discovery of JANUVIA (sitagliptin phosphate, compound 1),
      are described.

PMID- 17434733
TI  - Discovery of 1-(4-phenoxypiperidin-1-yl)-2-arylaminoethanone stearoyl-CoA
      desaturase 1 inhibitors.
AB  - A series of novel stearoyl-CoA desaturase 1 (SCD1) inhibitors were identified by
      scaffold design based on known SCD1 inhibitors. Large structural changes were
      made leading to multiple analogs with comparable or improved potency. This
      approach is valuable for generation of proprietary compounds without conducting a
      costly high-throughput screening.

PMID- 17434734
TI  - Potent and selective isophthalamide S2 hydroxyethylamine inhibitors of BACE1.
AB  - The design and synthesis of a novel series of potent BACE1 hydroxyethylamine
      inhibitors. These inhibitors feature hydrogen bonding substituents at the C-5
      position of the isophthalamide ring with improved selectivity over cathepsin D.

PMID- 17434735
TI  - Development of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones as
      orally active human chymase inhibitors.
AB  - A novel series of 6-benzyl substituted 4-aminocarbonyl-1,4-diazepane-2,5-diones
      was designed, synthesized, and evaluated as human chymase inhibitors. From this
      series, we identified several compounds which were effective, via oral
      administration, in a mouse model of chronic dermatitis.

PMID- 17434736
TI  - Synthesis and evaluation of 2'-substituted cyclobutyl nucleosides and nucleotides
      as potential anti-HIV agents.
AB  - A series of 2'-substituted cyclobutyl nucleoside analogs were efficiently
      prepared by constructing the core cyclobutyl ring using different [2+2]
      cycloaddition approaches. The triphosphate derivative of a cyclobutyl nucleoside
      was also synthesized and evaluated against wild-type and mutant HIV reverse
      transcriptases (RT). Whereas the nucleoside analogs were inactive against HIV-1
      in culture, the nucleotide showed good activity not only against wild-type and
      recombinant HIV RT (IC(50)=4.7, 6.9 microM), but also against the M184I and M184V
      mutants (IC(50)=6.1, 6.9 microM) in cell-free assays.

PMID- 17434737
TI  - The use of a daily goals sheet to improve communication in the paediatric
      intensive care unit.
AB  - OBJECTIVE: To assess the impact of the implementation of a daily goals sheet upon
      nursing perception of communication in an academic, tertiary care paediatric
      intensive care unit (PICU). DESIGN: Prospective, longitudinal, before-and-after
      intervention surveys. SETTING: University affiliated 12-bed PICU. SUBJECTS:
      Bedside nurses. INTERVENTIONS: A questionnaire was administered to PICU nurses
      addressing their perception of communication. Following this questionnaire, the
      use of a daily goals sheet was instituted. A second questionnaire was
      administered one year later. Mann-Whitney Rank Sum Test was used to compare
      differences of the graded outcome variables. MEASUREMENTS AND MAIN RESULTS: The
      primary outcome was the perception of communication taken from a nursing
      perspective. Eighty-five percent of nurses felt the daily goals sheet led to
      improved communication between physicians and nurses in the PICU. All questions
      related to communication demonstrated a positive influence of the goals sheet,
      with the perception of the PICU staff working as a team reaching statistical
      significance (p=0.05). The perception of the care of one surgical service being
      attending physician directed also significantly improved after the institution of
      the goals sheet (p=0.04). CONCLUSION: The institution of a daily goals sheet led
      to an improvement in nursing perception of communication. Future studies are
      required to determine if this change in process has a demonstrable effect on
      health care outcomes of critically ill children, or whether this tool can have
      the same beneficial effects in other academic and non-academic PICUs.

PMID- 17434738
TI  - Solitary cerebral metastasis from transitional cell carcinoma of the urinary
      tract.
AB  - We present a patient with a solitary cerebral metastasis from a transitional cell
      carcinoma of the right renal pelvis in the right occipital lobe with intratumoral
      hemorrhage. Despite aggressive multimodality management the patient died within 3
      months of presentation due to widespread systemic disease.

PMID- 17434739
TI  - Adaptive neuro-fuzzy inference system (ANFIS): a new approach to predictive
      modeling in QSAR applications: a study of neuro-fuzzy modeling of PCP-based NMDA
      receptor antagonists.
AB  - This paper proposes a new method, Adaptive Neuro-Fuzzy Inference System (ANFIS)
      to evaluate physicochemical descriptors of certain chemical compounds for their
      appropriate biological activities in terms of QSAR models with the aid of
      artificial neural network (ANN) approach combined with the principle of fuzzy
      logic. The ANFIS was utilized to predict NMDA (N-methyl-d-Aspartate) receptor
      binding activities of phencyclidine (PCP) derivatives. A data set of 38 drug-like
      compounds was coded with 1244 calculated molecular structure descriptors
      (clustered in 20 data sets) which were obtained from several sources, mainly from
      Dragon software. Prior to the progress to the ANFIS system, descriptors from the
      best subsets were selected using unsupervised forward selection (UFS) to
      eliminate redundancy and multicollinearity followed by fuzzy linear regression
      algorithm (FLR) which was used for variable selection. ANFIS was applied to train
      the final descriptors (Mor22m, E3s, R3v+, and R1e+) using a hybrid algorithm
      consisting of back-propagation and least-square estimation while the optimum
      number and shape of related functions were obtained through the subtractive
      clustering algorithm. Comparison of the proposed method with traditional methods,
      that is, multiple linear regression (MLR) and partial least-square (PLS) was also
      studied and the results indicated that the ANFIS model obtained from data sets
      achieved satisfactory accuracy.

PMID- 17434740
TI  - Synthesis and evaluation of amino-threoses in D- and L-series: are five membered
      ring amino-sugars more potent glycosidase inhibitors than the six membered ones?
AB  - Cyclic D- and L-4-aminothreose were synthesised from ethyl D- and L-tartrate,
      respectively. D-aminothreose was a potent inhibitor of alpha-glucosidase and of
      alpha-mannosidase. From the glycosidase inhibition potencies of the four 4-amino
      4-deoxy-tetroses, the contribution of binding of each functionality of the 5 and
      6 membered ring amino-sugars towards the various glycosidases is discussed.

PMID- 17434741
TI  - Speciation-dependent studies on removal of arsenic by iron-doped calcium alginate
      beads.
AB  - This work aims to study the differential attitude of Fe-doped calcium alginate
      (Fe-CA) beads towards As(III) and As(V) compounds so that speciation-dependent
      environmentally sustainable methodologies can be developed for removal of arsenic
      from contaminated water. Throughout the experiment, (76)As has been used as
      precursor of stable arsenic. The affinity of As(V) towards the Fe-CA beads is
      greater than that of As(III). Removal efficiency of Fe-CA beads for As(V)
      increases with increasing number of beads and longer shaking times. At pH 3, 30
      Fe-CA beads remove As(V) completely from a solution containing 20mgkg(-1) As(V).
      The technique has been successfully applied to the ground water collected from an
      arsenic-contaminated area.

PMID- 17434742
TI  - Triamcinolone suppresses retinal vascular pathology via a potent interruption of
      proinflammatory signal-regulated activation of VEGF during a relative hypoxia.
AB  - We examined the effect of triamcinolone acetonide (TA), a corticosteroid, on the
      relationship between vascular pathophysiology and vascular endothelial growth
      factor (VEGF) activation in the retina of a rat model of oxygen-induced
      retinopathy (OIR). OIR was induced by exposure of hyperoxia (80% oxygen) to
      Sprague-Dawley (SD) rats from P2 to P14 and then returned to normoxic conditions.
      TA was intravitreal-injected once into the right eye of OIR rats at P15. Effects
      of TA on vascular pathophysiology or changes of various genes in response to
      hypoxia and/or proinflammation under hypoxic retina were assessed by the Evans
      blue method, fluorescein isothiocyanate-dextran (FITC-D) infusion,
      immunoblotting, and ELIZA. TA not only reduced retinal neovascularization and
      vascular leakage in the OIR-rat retina, but also blocked the induction of hypoxia
      response proinflammatory genes before it negatively controlled VEGF activation.
      These findings suggest a potential that TA suppresses retinal neovascular
      pathophysiology via proinflammation-mediated activation of VEGF during hypoxia.

PMID- 17434743
TI  - Formation and geminate quenching of singlet oxygen in purple bacterial reaction
      center.
AB  - The phosphorescence of singlet oxygen ((1)X( *)) photosensitized by the
      carotenoidless reaction center (RC) of Rhodobacter sphaeroides R26.1 has been
      investigated, using H(2)O and D(2)O as the suspending media. To enhance (under
      neutral conditions) the triplet quantum yield of the special pair P(870) (P) by
      the radical pair mechanism, the quinone acceptor Q(A) was removed by means of a
      chemical treatment. The phosphorescence signal fits the functional form P(0)[exp
      (-t/tau)-exp(-t/zeta)], regardless of whether (1)X( *) is sensitized by P(dagger)
      or M(dagger) (where the dagger denotes triplet excitation and M is a water
      soluble molecule). The time constant zeta was identified with the decay time of
      (1)X( *); when P(dagger) is the sensitizer, one finds zeta(P)((1))=3.3+/-0.3
      micros, and zeta(P)((2))=34+/-3 micros, where the superscripts 1 and 2 refer to
      H(2)O and D(2)O, respectively; the corresponding values for sensitization by
      M(dagger) (in the absence of RC) are zeta(M)((1))=3.7+/-0.4 micros, and
      zeta(M)((2))=75+/-5 micros. The addition of RC's to the solution of M in D(2)O
      reveals that the RC is a quencher of (1)X( *); however, for equal concentrations
      of the RC, zeta(P)((2))<zeta(M)((2)), showing that (1)X( *) is deactivated, after
      its entry into the suspending medium, mainly by the solvent or the same RC which
      acts as the sensitizer. The values of tau(P) are similar in both solvents, ca. 2
      micros, but this time constant does not figure in the disappearance of P(dagger),
      which follows a bi-exponential course, alpha(1)exp(-t/tau(1))+alpha(2)exp(
      t/tau(2)). The time constants tau(1) and tau(2) (72+/-5 micros and 12+/-1 micros,
      respectively) as well as the factor alpha(2) are insensitive to the oxygen
      content, and quenching of P(dagger) is manifested only through a threefold
      reduction in the magnitude of alpha(1); these data imply the absence of dynamic
      quenching and heterogeneity of the RC. The mean lifetime of (1)X( *) inside the
      protein matrix is identified with tau(P), and the absence of a prompt component
      in the phosphorescence signal rationalized by proposing that the radiative decay
      of (1)X( *) within the RC is much slower than that in an aqueous environment.

PMID- 17434744
TI  - Diastereochemical differentiation of beta-amino acids using host-guest complexes
      studied by Fourier transform ion cyclotron resonance mass spectrometry.
AB  - Host-guest complexes where tetraethyl resorcarene was the host molecule were used
      to study the stereoselectivity of diasteromeric pairs of di-endo- and di-exo-2,3
      disubstituted norbornane and norbornene amino acids by ion-molecule reactions and
      collision-induced dissociation with electrospray ionization Fourier transform ion
      cyclotron resonance mass spectrometry (ESI FT-ICR MS). Both methods showed
      stereoselectivity for the diastereomeric pairs. Particularly high selectivity was
      achieved for di-endo- and di-exo-2,3-disubstituted norbornane amino acids with
      ion-molecule reactions. Also, ab initio and hybrid density functional theory
      calculations were performed to study the different structures of the host-guest
      complexes. Hydrogen bonding was crucial for the calculated lowest energy
      structures, and sterical considerations satisfactorily explained the ion-molecule
      reaction results.

PMID- 17434745
TI  - B-DNA helix stability in a solvent-free environment.
AB  - B-DNA is the most common DNA helix conformation under physiological conditions.
      However, when the amount of water in a DNA solution is decreased, B-to-A helix
      transitions have been observed. To understand what type of helix conformations
      exist in a solvent-free environment, a series of poly d(CG)(n) and mixed sequence
      DNA duplexes from 18 to 30 bp were examined with circular dichroism (CD), ESI-MS,
      ion mobility, and molecular dynamics. From the CD spectra, it was observed that
      all sequences had B-form helices in solution. However, the solvent-free results
      were more complex. For the poly d(CG)(n) series, the 18 bp duplex had an A-form
      helix conformation, both A- and B-helices were present for the 22 bp duplex, and
      only B-helices were observed for the 26 and 30 bp duplexes. Since these sequences
      were all present as B-DNA in solution, the observed solvent-free structures
      illustrate that smaller helices with fewer base pairs convert to A-DNA more
      easily than larger helices in the absence of solvent. A similar trend was
      observed for the mixed sequence duplexes where both an A- and B-helix were
      present for the 18 bp duplex, while only B-helices occur for the larger 22, 26,
      and 30 bp duplexes. Since the solvent-free B-helices appear at smaller sizes for
      the mixed sequences than for the pure d(CG)(n) duplexes, the pure d(CG)(n)
      duplexes have a greater A-philicity.

PMID- 17434746
TI  - Sizing large proteins and protein complexes by electrospray ionization mass
      spectrometry and ion mobility.
AB  - Mass spectrometry (MS) and ion mobility with electrospray ionization (ESI) have
      the capability to measure and detect large noncovalent protein-ligand and protein
      protein complexes. Using an ion mobility method of gas-phase electrophoretic
      mobility molecular analysis (GEMMA), protein particles representing a range of
      sizes can be separated by their electrophoretic mobility in air. Highly charged
      particles produced from a protein complex solution using electrospray can be
      manipulated to produce singly charged ions, which can be separated and quantified
      by their electrophoretic mobility. Results from ESI-GEMMA analysis from our
      laboratory and others were compared with other experimental and theoretically
      determined parameters, such as molecular mass and cryoelectron microscopy and X
      ray crystal structure dimensions. There is a strong correlation between the
      electrophoretic mobility diameter determined from GEMMA analysis and the
      molecular mass for protein complexes up to 12 MDa, including the 93 kDa enolase
      dimer, the 480 kDa ferritin 24-mer complex, the 4.6 MDa cowpea chlorotic mottle
      virus (CCMV), and the 9 MDa MVP-vault assembly. ESI-GEMMA is used to
      differentiate a number of similarly sized vault complexes that are composed of
      different N-terminal protein tags on the MVP subunit. The average effective
      density of the proteins and protein complexes studied was 0.6 g/cm(3). Moreover,
      there is evidence that proteins and protein complexes collapse or become more
      compact in the gas phase in the absence of water.

PMID- 17434747
TI  - Endocannabinoids limit metabotropic glutamate 5 receptor-mediated synaptic
      inhibition of striatal principal neurons.
AB  - Synaptic transmission in the striatum is regulated by metabotropic glutamate
      (mGlu) receptors through pre- and postsynaptic mechanisms. We investigated the
      involvement of mGlu 1 and 5 receptors in the control of both excitatory and
      inhibitory transmission in the striatum. The mGlu 1 and 5 receptor agonist 3,5
      DHPG failed to affect glutamate transmission, while it caused a biphasic effect
      on GABA transmission, characterized by early increase and late decrease in the
      frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from
      striatal principal neurons. Both mGlu 1 and 5 receptors were involved in the
      early response to 3,5-DHPG, through membrane depolarization of striatal GABAergic
      interneurons and action potential generation. The 3,5-DHPG-mediated late
      depression of inhibitory inputs to striatal principal neurons was conversely
      secondary to mGlu 5 receptor activation and subsequent endocannabinoid release.
      In conclusion, we have identified an mGlu-dependent mechanism of GABA
      transmission regulation of potential relevance for physiological neuronal
      activity.

PMID- 17434748
TI  - Mouse Aurora A: expression in Escherichia coli and purification.
AB  - Aurora kinases have recently become some of the most intensely pursued oncology
      targets for the design of small-molecule inhibitors. Most of the active Aurora-A
      protein variants are currently being expressed from baculoviruses in insect
      cells, while catalytically impaired proteins can also be generated in and
      purified from Escherichia coli. In this study we present a method of expressing
      large quantities of active mouse Aurora-A kinase domain as an N-terminal
      glutathione-S-transferase fusion protein in bacteria and outline a simple
      purification method that produces greater than 99% pure protein samples suitable
      for enzymatic assays and X-ray crystallography. The methods described in this
      report simplify mouse Aurora-A expression and purification, and may aid in the
      production of other difficult kinases in prokaryotes.

PMID- 17434749
TI  - Purification of CK1 by affinity chromatography on immobilised axin.
AB  - Members of the Casein Kinase 1 (CK1) family are implicated in the regulation of a
      variety of physiological processes like development and circadian rhythm, as well
      as in diseases like cancer and Alzheimer's disease. From that perspective, CK1
      family members are interesting targets for potential chemotherapy. We describe
      here a rapid and efficient method for the purification of CK1 by affinity
      chromatography on an immobilised fragment of axin. Axin is a scaffolding protein
      that interacts with a multitude of proteins, amongst them APC, GSK-3, beta
      catenin, CK1alpha, delta, and epsilon, and PP2A. A GST-tagged axin peptide
      (residues 495-684) was produced in Escherichia coli and either immobilised on
      glutathione agarose beads or purified and immobilised on CNBr-activated sepharose
      4B. These "GST-axin" matrices were found to selectively bind native CK1alpha and
      CK1epsilon from porcine brain. The affinity-purified enzymes displayed high
      kinase activity. This single step purification method provides a convenient tool
      to efficiently purify large amounts of active native CK1 for screening purposes.
      This single step purification method also provides a convenient tool to follow
      the status of the axin-binding CK1 isoforms alpha, delta, and epsilon (protein
      levels, composition of isoforms, kinase activity) under different physiological
      settings.

PMID- 17434750
TI  - Expression and purification of catalytically active human PHD3 in Escherichia
      coli.
AB  - Transcription factor HIF-1 is a key regulator in cellular adaptation to hypoxia.
      HIF prolyl hydroxylases (PHDs) control HIF-1 accumulation by hydroxylation
      dependent on molecular oxygen. Due to this regulation, PHDs have been pointed out
      as potential drug targets. We have purified catalytically active human PHD3 after
      heterologous expression in Escherichia coli. Histidine-tagged enzyme was isolated
      as monomer by immobilized Ni-affinity chromatography followed by gel filtration.
      Overexpression of bacterial chaperonins GroEL/ES at 30 degrees C substantially
      increased the yield of soluble PHD3. High concentrations of salt and reducing
      agent during purification prevented protein aggregation. The enzyme activity with
      peptide derived from HIF-1alpha was inhibited by Zn(2+), desferrioxamine and
      imidazole. The hydroxylation activity was verified by mass spectrometry, and
      Pro567 in HIF-1alpha was discovered as a new site of hydroxylation.

PMID- 17434751
TI  - The protective effect of marriage on mortality in a dynamic society.
AB  - PURPOSE: We sought to assess whether the protective effect of marriage on overall
      and cause-specific mortality has changed over time in a dynamic society. METHODS:
      Data from the census-based Israel Longitudinal Studies (ILMS) I (1983-1992) and
      II (1995-2004) were analyzed. Cox proportional hazard modeling adjusting for
      sociodemographic factors was applied to 152,150 and 209,125 individuals, ages 45
      89 years from the ILMS I and II, respectively. During each study period 31,749
      (ILMS I) and 37,656 (ILMS II) deaths were reported. RESULTS: Mortality
      inequalities by marital status remained significant and widened over time for
      middle-aged and elderly men and women. Changes in cause-specific mortality
      indicated a widening of cardiovascular disease mortality inequalities by marital
      status. An increasing trend was also noted for deaths from cancer (+25%) and
      other causes (+38%, p < 0.05) in middle-aged men, but not women (cancer = 0%;
      other causes = -3%). CONCLUSIONS: The stronger beneficial effect of marriage over
      time may reflect societal changes that have differentially affected men and
      women.

PMID- 17434752
TI  - Does quality of care for cardiovascular disease and diabetes differ by gender for
      enrollees in managed care plans?
AB  - PURPOSE: To assess gender differences in the quality of care for cardiovascular
      disease and diabetes for enrollees in managed care plans. METHODS: We obtained
      data from 10 commercial and 9 Medicare plans and calculated performance on 6
      Health Employer Data and Information Set (HEDIS) measures of quality of care
      (beta-blocker use after myocardial infarction [MI], low-density lipoprotein
      cholesterol [LDL-C] check after a cardiac event, and in diabetics, whether
      glycosylated hemoglobin [HgbA1c], LDL cholesterol, nephropathy, and eyes were
      checked) and a 7th HEDIS-like measure (angiotensin-converting enzyme [ACE]
      inhibitor use for congestive heart failure). A smaller number of plans provided
      HEDIS scores on 4 additional measures that require medical chart abstraction
      (control of LDL-C after cardiac event, blood pressure control in hypertensive
      patients, and HgbA1c and LDL-C control in diabetics). We used logistic regression
      models to adjust for age, race/ethnicity, socioeconomic status, and plan. MAIN
      FINDINGS: Adjusting for covariates, we found significant gender differences on 5
      of 11 measures among Medicare enrollees, with 4 favoring men. Similarly, among
      commercial enrollees, we found significant gender differences for 8 of 11
      measures, with 6 favoring men. The largest disparity was for control of LDL-C
      among diabetics, where women were 19% less likely to achieve control among
      Medicare enrollees (relative risk [RR] = 0.81; 95% confidence interval [CI] =
      0.64-0.99) and 16% less likely among commercial enrollees (RR = 0.84; 95%CI =
      0.73-0.95). CONCLUSION: Gender differences in the quality of cardiovascular and
      diabetic care were common and sometimes substantial among enrollees in Medicare
      and commercial health plans. Routine monitoring of such differences is both
      warranted and feasible.

PMID- 17434753
TI  - Eosinophilic granule cells and endocytic cells in intestinal wall of pearl
      gouramy (Anabantidae: Teleostei).
AB  - The localization and frequency of eosinophilic granule cells (EGCs) and endocytic
      cells in the intestinal wall of a teleost, pearl gouramy (Trichogaster leeri), a
      stomach-containing anabantid, are described. EGCs occurred in high numbers in
      lamina propria and epithelial layer throughout the entire intestine. They often
      embraced blood capillaries, but were unable to take up foreign ferritin, i.e.
      they seem not to play any blood cleansing role in this tissue. Only some of the
      EGCs granules reacted with Schmorl's solution, suggesting that they are at a
      different stage of development or of different types in these cells. The granule
      content is probably secreted close to the intestine blood stream where it may
      play important local immunological roles. The present results suggest that the
      number of intestinal EGCs can be high in teleosts even in species with a putative
      well-developed acid-based defence in the digestive tract. Also, endocytic cells
      capable of taking up and storing much foreign ferritin were frequently seen in
      this tissue; such cells may play significant cleansing and scavenger roles
      throughout the entire intestine in pearl gouramy.

PMID- 17434754
TI  - Assessment of repeatability of surface electromyography signals by singular value
      decomposition.
AB  - Singular value decomposition (SVD) of full-wave rectified surface
      electromyography (sEMG) signals was investigated for repeatability indices of
      sEMG linear envelopes (LE) during biceps curl. The SVD based repeatability
      indices were compared with a well-known method, the variance ratio (VR). The
      usefulness of the offered indices was examined by a simulation and it was applied
      to the sEMG LEs. The results have shown that the VRs were correlated with the SVD
      based indices significantly. The usefulness of the offered indices on real world
      EMG signals practically comes from decreasing amplitudes of the first few
      singular values of EMG LE matrix. If repeatability is high, singular values decay
      fast and vice versa. If justified by further researches, the offered indices may
      be used practically for repeatability measurement of sEMG LEs.

PMID- 17434755
TI  - Time- and frequency-domain monitoring of the myoelectric signal during a long
      duration, cyclic, force-varying, fatiguing hand-grip task.
AB  - The amplitude and mean power spectral frequency (MNF) of the electromyogram (EMG)
      of flexor digitorum superficialis and extensor carpi radialis muscles were
      monitored during cyclic, force-varying, constant-posture, submaximal, grip-force
      contractions until endurance. These contractions are reminiscent of work tasks
      associated with the risk of repetitive stress injuries. Based on recommendations
      from a prior cross-comparison study of these data, the cyclic grip-force
      contractions were temporally aligned cycle-by-cycle to the achieved grip force
      profile, then EMG amplitude was computed using signal whitening (500 ms window)
      and MNF was computed using the short-time Fourier transform (500 ms window). In
      addition, brief (8s) constant-force (static) contractions were interspersed
      within the cyclic contractions every 5 min. MNF was tracked during these periods.
      All subjects reported a marked increase in pain/discomfort/fatigue during the
      contraction trials, until self-selecting to discontinue contractions after 30-90
      min. Discomfort returned to near-baseline levels during the ensuing 45 min
      recovery (rest) period. No statistical trend was found in either EMG amplitude or
      MNF during the cyclic contractions or the recovery period. Initial MNF and MNF
      slope were monitored during the 8s interspersed static contractions. These
      parameters also did not follow any consistent trend. These results indicate
      limitations in the use of these EMG descriptors for assessment of fatigue during
      long-duration, force-varying contractions.

PMID- 17434756
TI  - Hippocampal shape analysis in Alzheimer's disease: a population-based study.
AB  - BACKGROUND: Hippocampal atrophy--particularly of the CA1 region--may be useful as
      a biomarker for Alzheimer's disease (AD) or the risk for AD. The extent to which
      the AD hippocampus can be distinguished in vivo from changes due to normal aging
      or other processes that affect the hippocampus is of clinical importance and is
      an area of active research. In this study, we use structural imaging techniques
      to model hippocampal size and regional shape differences between elderly men with
      incident AD and a non-demented comparison group of elderly men. METHODS:
      Participants are Japanese-American men from the Honolulu Asia Aging Study (HAAS).
      The HAAS cohort has been followed since 1965. The following analysis is based on
      a sub-group of men who underwent MRI examination in 1994-1996. Participants were
      diagnosed with incident AD (n=24: age=82.5+/-4.6) or were not demented (n=102:
      age=83.0+/-5.9). One reader, blinded to dementia diagnosis, manually outlined the
      left and right hippocampal formation using published criteria. We used 3D
      structural shape analysis methods developed at the Laboratory of Neuro Imaging
      (LONI) to compare regional variation in hippocampal diameter between the AD cases
      and the non-demented comparison group. RESULTS: Mean total hippocampal volume was
      11.5% smaller in the AD cases than the non-demented controls (4903+/-857 mm(3)
      vs. 5540+/-805 mm(3)), with a similar size difference for the median left (12.0%)
      and median right (11.6%) hippocampus. Shape analysis showed a regional pattern of
      shape difference between the AD and non-demented hippocampus, more evident for
      the hippocampal body than the head, and the appearance of more consistent
      differences in the left hippocampus than the right. While assignment to a
      specific sub-region is not possible with this method, the surface changes
      primarily intersect the area of the hippocampus body containing the CA1 region
      (and adjacent CA2 and distal CA3), subiculum, and the dentate gyrus-hilar region.

PMID- 17434757
TI  - Amplitude of low frequency fluctuation within visual areas revealed by resting
      state functional MRI.
AB  - Most studies of resting-state functional magnetic resonance imaging (fMRI) have
      applied the temporal correlation in the time courses to investigate the
      functional connectivity between brain regions. Alternatively, the power of low
      frequency fluctuation (LFF) may also be used as a biomarker to assess spontaneous
      activity. The purpose of the current study is to evaluate whether the amplitude
      of the LFF (ALFF) relates to cerebral physiological states. Ten healthy subjects
      underwent four resting-state fMRI scanning sessions, two for eyes-open (EO) and
      two for eyes-closed (EC) conditions, with two sets of parameters (TR=400 ms and 2
      s, respectively). After data preprocessing, ALFF was obtained by calculating the
      square root of the power spectrum in the frequency range of 0.01-0.08 Hz. Our
      results showed that the ALFF in EO was significantly higher than that in EC
      (P<0.05, corrected) in the bilateral visual cortices. Furthermore, the ALFF in EO
      was significantly reduced in the right paracentral lobule (PCL) than in EC
      (P<0.05, corrected). Region of interest (ROI) analysis showed that the ALFF
      differences between EO and EC were consistent for each subject. In contrast, no
      significant ALFF differences were found between EO and EC (P<0.381) in the
      posterior cingulate cortex. All these results agree well with previous studies
      comparing EO and EC states. Our finding of the distinct ALFF difference between
      EO and EC in the visual cortex implies that the ALFF may be a novel biomarker for
      physiological states of the brain.

PMID- 17434758
TI  - A congruent molecular signature of vicariance across multiple plant lineages.
AB  - Explaining disjunct distributions, or why closely related organisms are often
      separated by apparently severe barriers such as oceans or deserts, is a great
      challenge for historical biogeography. Competing explanations are long-distance
      dispersal across a barrier, and vicariance, in which disjunct taxa are descended
      from an ancestral population that was split by formation of the barrier.
      Vicariance explanations are testable by their prediction that near-simultaneous
      speciation should have occurred across multiple lineages of organisms between the
      disjunct areas because the origin of a barrier would potentially disrupt gene
      flow within multiple species. To date, there have been few studies providing
      evidence for multiple synchronous ancient divergences across a barrier whose
      origin coincides with the timing of the speciation events. Here, we use relaxed
      molecular-clock dating to investigate the timing of south-western (SW) versus
      south-eastern (SE) divergences in 23 pairs of plant lineages in southern
      Australia. Sixteen of the divergences correlate with the origin, 13-14 million
      years (Myr) ago, of the arid treeless Nullarbor Plain. The Nullarbor Plain
      currently forms a substantial barrier to SW-SE migration but during the last
      45Myr this region has experienced multiple episodes of marine inundation and
      subaerial exposure. Thus, there have been multiple events that could have caused
      either isolation and speciation, or secondary contact, among the taxa of southern
      Australia. The strong molecular signal of coincident speciation in many diverse
      lineages during a short period provides the best evidence to date linking
      synchronous speciation to an ancient vicariance event.

PMID- 17434759
TI  - Why weight?
AB  - Whether phylogenetic data should be differentially or equally weighted is
      currently debated. Further, if differential weighting is to be explored, there is
      no consensus among investigators as to which weighting scheme is most
      appropriate. Mitochondrial genome data offer a powerful tool in assessment of
      differential weighting schemes because taxa can be selected from which a highly
      corroborated phylogeny is available (so that accuracy can be assessed), and it
      can be assumed that different data partitions share the same history (so that
      gene-sorting issues are not so problematic). Using mitochondrial data from 17
      mammalian genomes, we evaluated the most commonly used weighting schemes, such as
      successive weighting, transversion weighting, codon-based weighting, and amino
      acid coding, and compared them to more complex weighting schemes including a 6
      parameter weighting, pseudoreplicate reweighting, and tri-level weighting. We
      found that the most commonly used weighting schemes perform the worst with these
      data. Some of the more complex schemes perform well, however, none of them is
      consistently superior. These results support ones biases; if one has a
      predilection to avoid differential weighting, these data support equally weighted
      parsimony and maximum likelihood. Others might be encouraged by these results to
      try weighting as a form of data exploration.

PMID- 17434760
TI  - Patterns of gene duplication and functional diversification during the evolution
      of the AP1/SQUA subfamily of plant MADS-box genes.
AB  - Members of the AP1/SQUA subfamily of plant MADS-box genes play broad roles in the
      regulation of reproductive meristems, the specification of sepal and petal
      identities, and the development of leaves and fruits. It has been shown that
      AP1/SQUA-like genes are angiosperm-specific, and have experienced several major
      duplication events. However, the evolutionary history of this subfamily is still
      uncertain. Here, we report the isolation of 14 new AP1/SQUA-like genes from seven
      early-diverging eudicots and the identification of 11 previously uncharacterized
      ESTs and genomic sequences from public databases. Sequence comparisons of these
      and other published sequences reveal a conserved C-terminal region, the FUL
      motif, in addition to the known euAP1/paleoAP1 motif, in AP1/SQUA-like proteins.
      Phylogenetic analyses further suggest that there are three major lineages (euAP1,
      euFUL, and AGL79) in core eudicots, likely resulting from two close duplication
      events that predated the divergence of core eudicots. Among the three lineages,
      euFUL is structurally very similar to FUL-like genes from early-diverging
      eudicots and basal angiosperms, whereas euAP1 might have originally been
      generated through a 1-bp deletion in the exon 8 of an ancestral euFUL- or FUL
      like gene. Because euFUL- and FUL-like genes usually have broad expression
      patterns, we speculate that AP1/SQUA-like genes initially had broad functions.
      Based on these observations, the evolutionary fates of duplicate genes and the
      contributions of the frameshift mutation and alternative splicing to functional
      diversity are discussed.

PMID- 17434761
TI  - Molecular phylogenetics and the evolution of host plant associations in the
      nematode genus Fergusobia (Tylenchida: Fergusobiinae).
AB  - Fergusobia nematodes (Tylenchida: Fergusobiinae) and Fergusonina flies (Diptera:
      Fergusoninidae) are putative mutualists that develop together in galls formed in
      meristematic tissues of many species of the plant family Myrtaceae in
      Australasia. Fergusobia nematodes were sampled from a variety of myrtaceous hosts
      and gall types from Australia and one location in New Zealand between 1999 and
      2006. Evolutionary relationships of these isolates were inferred from
      phylogenetic analyses of the DNA sequences of the nuclear ribosomal DNA near-full
      length small subunit (up to 1689bp for 21 isolates), partial large subunit D2/D3
      domain (up to 889bp for 87 isolates), partial mitochondrial cytochrome oxidase
      subunit I (618 bp for 82 isolates), and combined D2/D3 and mtCOI (up to 1497bp
      for 66 isolates). The SSU data supported a monophyletic Fergusobia genus within a
      paraphyletic Howardula. A clade of Drosophila-associated Howardula, including
      Howardula aoronymphium, was the closest sequenced sister group. Phylogenetic
      analysis of sequences from D2/D3 and mtCOI, separately and combined, revealed
      many monophyletic clades within Fergusobia. The relationships inferred by D2/D3
      and mtCOI were congruent with some exceptions. Well-supported clades were
      generally consistent with host plant species and gall type. However, phylogenetic
      analysis suggested host switching or putative hybridization events in many
      groups, except the lineage of shoot bud gallers on the broad-leaved Melaleuca
      species complex.

PMID- 17434762
TI  - Cryptic speciation in marine sponges evidenced by mitochondrial and nuclear
      genes: a phylogenetic approach.

PMID- 17434763
TI  - Which relationship does osteoarthritis share with smoking?

PMID- 17434764
TI  - Systematic reviews in endodontics--examples of GIGO?

PMID- 17434765
TI  - A pedigree with autosomal dominant thrombocytopenia, red cell macrocytosis, and
      an occurrence of t(12:21) positive pre-B acute lymphoblastic leukemia.
AB  - Sampling and analyzing new families with inherited blood disorders are major
      steps contributing to the identification of gene(s) responsible for normal and
      pathologic hematopoiesis. Familial occurrences of hematological disorders alone,
      or as part of a syndromic disease, have been reported, and for some the
      underlying genetic mutation has been identified. Here we describe a new autosomal
      dominant inherited phenotype of thrombocytopenia and red cell macrocytosis in a
      four-generation pedigree. Interestingly, in the youngest generation, a 2-year-old
      boy presenting with these familial features has developed acute lymphoblastic
      leukemia characterized by a t(12;21) translocation. Tri-lineage involvement of
      platelets, red cells and white cells may suggest a genetic defect in an early
      multiliear progenitor or a stem cell. Functional assays in EBV-transformed cell
      lines revealed a defect in cell proliferation and tubulin dynamics. Two candidate
      genes, RUNX1 and FOG1, were sequenced but no pathogenic mutation was found.
      Identification of the underlying genetic defect(s) in this family may help in
      understanding the complex process of hematopoiesis.

PMID- 17434766
TI  - Abnormal permeability pathways in human red blood cells.
AB  - A number of situations that result in abnormal permeability pathways in human red
      blood cells (RBCs) have been investigated. In sickle cell disease (SCD), RBCs
      contain HbS, rather than the normal HbA. When deoxygenated, an abnormal
      conductance pathway, termed P(sickle), is activated, which contributes to cell
      dehydration, largely through allowing Ca(2+) entry and subsequent activation of
      the Gardos channel. Whole-cell patch-clamp recordings from sickle RBCs show a
      deoxygenated-induced conductance, absent from normal RBCs, which shares some of
      the properties of P(sickle): equivalent Na(+) and K(+) permeability, significant
      Ca(2+) conductance, partial inhibition by DIDS and also Zn(2+). Gd(3+) markedly
      attenuates conductance in both normal and sickle RBCs. In addition, deoxygenated
      sickle cells, but not oxygenated ones or normal RBCs regardless of the oxygen
      tension, undergo haemolysis in isosmotic non-electrolyte solutions. Non
      electrolyte entry was confirmed radioisotopically whilst haemolysis was inhibited
      by DIDS. These findings suggest that under certain circumstances P(sickle) may
      also be permeable to non-electrolytes. Finally, RBCs from certain patients with
      hereditary stomatocytosis have a mutated band 3, which appears able to act as a
      conductance pathway for univalent cations. These results extend our understanding
      of the abnormal permeability pathways of RBCs.

PMID- 17434767
TI  - Further musings on some red blood cell problems for perspicacious physiologists.

PMID- 17434768
TI  - Human B lymphocytes and non-Hodgkin's lymphoma cells become polyploid in response
      to the protein kinase inhibitor SU6656.
AB  - We show that prolonged exposure of non-Hodgkin's lymphoma (NHL) cell lines to low
      doses of the Src family protein tyrosine kinases (SFKs) inhibitor SU6656 caused
      proliferation abrogation as a result of the formation of cells with single
      multilobed nuclei and several mitotic spindle poles, features similar to
      polyploid megakaryocytes. The propensity of the NHL B cells tested to undergo
      polyploid was unrelated to the presence of p53 mutations in these cells since
      comparable outcomes were observed in SU6656-exposed cultures of blood B
      lymphocytes derived from healthy individuals. Thus, in addition to its utility
      for the study of megakaryocyte polyploidization, our results show that SU6656 can
      also induce polyploidy in cells of lymphoid origin, revealing a chemotherapeutic
      potential for this inhibitor to limit tumor propagation of malignant B cell
      lymphomas, although not without affecting normal B cells as well.

PMID- 17434769
TI  - Chloride channels in normal and cystic fibrosis human erythrocyte membrane.
AB  - Electrophysiological studies on human RBCs have been difficult due to fragility
      and small size of cells, and little is known of ionic conductive pathways present
      in the RBC membrane in health and disease. We report on anionic channels in cells
      of healthy donors (control) and cystic fibrosis (CF) patients. Anion channel
      activity (8-12 pS, linear) was induced in cell-attached configuration by
      forskolin (50 microM) and in excised inside-out configuration by PKA (100 nM) and
      ATP (1 mM) but control and CF RBCs differed by their respective kinetics and
      gating properties. These channels were permeable to ATP (100 mM, symmetrical Tris
      ATP). These data suggest either the existence of two different anionic channel
      types or regulation of a single channel type either by the CFTR (cystic fibrosis
      transmembrane regulator) protein or by different cytosolic factors. Another
      anionic channel type displaying outward rectification (approximately 80 pS,
      outward conductance) was present in 30% of CF cell patches but was not observed
      in normal cell patches. The frequently recorded activity of this channel in CF
      patches suggests a down-regulation in normal RBCs.

PMID- 17434770
TI  - Fourier-based spatial mapping of oscillatory phenomena in fungi.
AB  - Microorganisms display a range of oscillatory phenomena that operate over
      different temporal scales. Fourier analysis provides a compact description of
      such oscillations in terms of their frequency, magnitude and phase. However, in
      the majority of studies there is no explicit consideration of the spatial
      organisation of the oscillation. Here we describe procedures and a software
      package to map oscillatory phenomena in microorganisms in both the time and
      frequency domains. Key parameters of interest, such as frequency, phase or
      magnitude of the oscillations, are presented as pseudo-colour coded maps. This
      maintains the spatial information in the image and greatly facilitates
      understanding of potentially complex propagating waves or development of
      oscillatory domains with distinct behaviour. We illustrate the utility of this
      system with reference to spatial analysis of the pulsatile component to amino
      acid transport in mycelial systems of Phanerochaete velutina and Coniophora
      puteana, and actin-myosin based contractions in Physarum polycephalum.

PMID- 17434771
TI  - The neurological evolution of Pearson syndrome: case report and literature
      review.
AB  - BACKGROUND: Pearson syndrome (PS) is an uncommon specific syndrome among
      mitochondrial diseases. It has unique clinical presentations. AIMS: The purpose
      of this article is to clarify the neurological evolution, neuroimage findings,
      molecular genetic analysis and outcomes in PS cases with neurologic
      manifestations. METHODS: We described the clinical progress of a female patient
      who was diagnosed as PS with a novel 6.0 kbp mitochondrial DNA deletion. She had
      typical clinical features of PS in early infancy followed by multiple organs
      involvement after the age of 1 year. At age 3, Kearns-Sayre syndrome (KSS) and
      Leigh syndrome (LS) developed. We also reviewed PS cases reported in the
      literature and analyzed the neurological evolution. RESULTS: Total 55 PS cases,
      including our index case, had been reported. Among them, 11 cases had detailed
      clinical descriptions in terms of hypotonia, developmental delay, ataxia or
      tremor. In whom, PS might evolve into KSS and/or LS: three cases evolving into
      KSS; one case on the transition of KSS; three cases evolve into LS; our index
      case has both presentations. The neuroimage findings of PS were quite different
      which might be from normal to specific abnormal findings over the cerebral white
      matter, cerebellum, basal ganglion and brainstem. Among those cases, the
      molecular analysis revealed large-scale mitochondrial deletion around 3.1-6.0kbp.
      The outcome of PS was opposite: either early death before age 4 or survived
      beyond age 7. CONCLUSIONS: The neurological features of PS have potential
      evolution changes that are from normal, mild neurological deficits to special
      mitochondrial syndromes: KSS and LS. Closely monitoring neurological symptoms,
      arranging eye fundus examinations and neuroimaging studies in cases with changes
      of neurological signs are crucial.

PMID- 17434772
TI  - Simulation of 4D spectral-spatial EPR images.
AB  - Electron paramagnetic resonance imaging (EPRI) can be modeled by the forward
      projection of a 4D synthetic spectral-spatial phantom. We developed a simulation
      tool for EPRI and carried out a quantitative comparison between simulation and
      experiment, focusing on the signal and noise characteristics. The signal height
      in the simulation was compared to that in the experimental projections at
      gradients of different magnitudes and directions. We investigated the noise power
      spectrum of an EPR imager and incorporated it into the simulation. The signal and
      noise modeling of the simulation achieved the same performance as the EPR imager.
      Using this simulation, various sampling schemes were tried to find an optimized
      parameter set under the customized noise model of this EPR imager.

PMID- 17434773
TI  - Primary versus secondary intraocular lens placement after pars plana lensectomy
      in pediatric Marfan syndrome.

PMID- 17434774
TI  - Patterns of eye care use and expenditures among children with diagnosed eye
      conditions.
AB  - PURPOSE: Little is known about use and expenditure patterns of children's eye
      care services and about possible disparities in care among children. This report
      describes the use and expenditure patterns of eye care and non-eye care services
      for children under 18 years old in the United States. METHODS: Levels of use and
      expenditure were estimated using self-reported information from the nationally
      representative Medical Expenditure Panel Surveys (1996-2001) for 48,304 subjects
      under 18 years old from randomly selected households in the United States. Means
      presented for children with and without diagnosed eye conditions were adjusted
      for child and family characteristics using generalized linear models. RESULTS:
      Children with diagnosed eye conditions had higher levels of use and expenditure
      than children without diagnosed conditions. Families of children with diagnosed
      eye conditions incurred higher out-of-pocket expenditures. Black children and
      children living below 400% of the federal poverty level had lower levels of use
      and expenditure, indicating that they received fewer and less intensive services.
      CONCLUSIONS: Children with diagnosed eye conditions experienced higher overall
      use of health care. Some groups of children appear to be underserved. Estimates
      of use and expenditure patterns, stratified by socioeconomic factors, will be
      needed to plan for future delivery of children's eye and vision care services and
      to assess progress toward Healthy People 2010 goals.

PMID- 17434775
TI  - The effect of strabismus surgery on retrobulbar hemodynamics.
AB  - PURPOSE: To investigate the potential alterations of ocular hemodynamics after
      strabismus surgery using color Doppler ultrasonography. MATERIALS AND METHODS:
      Twenty eyes of 18 patients and the left eyes of 20 healthy age- and sex-matched
      volunteers were evaluated. Patients were divided into two groups according to the
      number of operated muscles. Group 1 included seven patients with surgery on one
      rectus muscle; group 2 included 13 patients with surgery on two rectus muscles.
      Nine patients underwent adjustable suture eye muscle surgery. The ophthalmic
      artery, central retinal artery, short posterior ciliary artery, long posterior
      ciliary artery, and central retinal veins of both groups were examined. With
      spectral analysis, peak systolic velocity, end-diastolic velocity, resistivity,
      and pulsatility indices were calculated. RESULTS: There was no difference in the
      Doppler ultrasonography parameters between the group with surgery on one
      horizontal rectus muscle and the group with surgery on two-horizontal rectus
      muscles. The adjustable suture procedure did not affect retrobulbar hemodynamics.
      There was no difference between the preoperative and postoperative Doppler
      examinations. CONCLUSIONS: In contrast with some recent studies, our results
      suggest that the strabismus surgery involving one- or two-horizontal rectus
      muscles does not have a measurable effect on retrobulbar blood flow.

PMID- 17434778
TI  - 3-hydroxyacyl-CoA dehydrogenase (HAD) deficiency replaces short-chain hydroxyacyl
      CoA dehydrogenase (SCHAD) deficiency as well as medium- and short-chain
      hydroxyacyl-CoA dehydrogenase (M/SCHAD) deficiency as the consensus name of this
      fatty acid oxidation disorder.

PMID- 17434777
TI  - Comparison of age-related differences in expression of antioxidant enzyme mRNA
      and activity in various tissues of pigs.
AB  - Antioxidant enzymes (AOEs), glutathione peroxidase (GPx), superoxide
      dismutase(SOD) and catalase (CAT) play an important role in protecting tissues
      from reactive oxygen species (ROS) reactions. The objective of this study was to
      determine the developmental regulation of AOEs mRNA levels and activity in
      tissues of different growing phases pigs (Sus scrofa). Nine different tissues
      were collected from thirty Duroc x Landrace x Yorkshire male pigs with six
      animals in each age (1, 42, 84, 126 and 168 days) to assay for GPx, CAT and
      CuZnSOD mRNA expression and activities. Results showed that GPx, CAT, and CuZnSOD
      mRNA levels in liver increased (P<0.05) at the first stage, and thereafter their
      levels began to decline (P<0.05), and the maximal mRNA levels of these AOEs were
      seen at the age of 42, 84, and 126 days, respectively. In Muscle, GPx and CAT
      mRNA level increased from 1 to 84 days and 1 to 126 days, respectively, and
      thereafter their levels began to decline, whereas CuZnSOD mRNA level steadily
      increased (P<0.05) following birth. Activity expression of AOEs in selected
      tissues was increased as pigs became older (P<0.05) with the exception of CuZnSOD
      activity in muscle, but changes in AOEs mRNA levels between ages did not fully
      account for all changes in activity. GPx and CuZnSOD mRNA were most abundantly
      expressed in muscle, while CAT mRNA were most abundant in brain. AOEs may exert
      cell and tissue-specific roles in metabolic regulation beyond their mere
      antioxidant potential. In conclusion, expression of AOEs mRNA and activity
      exhibit different developmental profiles in various tissues of pigs, and the
      regulation of AOEs is not tightly coordinated in either tissue.

PMID- 17434779
TI  - Mutations in MYOZ1 as well as MYOZ2 encoding the calsarcins are not associated
      with idiopathic and familial dilated cardiomyopathy.

PMID- 17434776
TI  - Monocular activation of V1 and V2 in amblyopic adults measured with functional
      magnetic resonance imaging.
AB  - PURPOSE: Although previous neuroimaging efforts clearly indicate visual cortical
      dysfunction in adults with amblyopia, the extent of abnormalities remains
      unclear. METHODS: This functional magnetic resonance imaging (fMRI) study
      directly compared activity in visual cortex produced by monocular stimulation in
      18 adults (six esotropic strabismics, six anisometropes, and six controls).
      Measures were made in three cortical regions-of-interest, individually defined
      using standard retinotopic mapping techniques in the nonamblyopic eye,
      corresponding to extrafoveal V1, extrafoveal V2, and the foveal representation at
      the occipital pole. Fixation stability was monitored and found not to differ
      significantly between subject groups. RESULTS: Overall results showed depressed
      fMRI signal magnitude for amblyopic eyes compared with sound eyes, although a few
      subjects did not show this trend. Assessment of the spatial extent of activation
      using an ocular dominance index did show significantly larger interocular
      differences for both strabismics and anisometropes compared with control subjects
      for whom eye dominance was carefully defined. In addition, both amblyopic groups
      showed less cortical area able to be significantly driven by either eye. The
      magnitude of these effects was equivalent in V1, V2, and the foveal
      representation, as well as between amblyopic groups. No difference was detected
      in the strength of signal from the nasal versus temporal retina in either
      amblyopic group. CONCLUSIONS: Asymmetries in magnitude of monocular activation do
      occur in subjects with amblyopia, but these basic measures are limited in terms
      of sensitivity for mild to moderate amblyopia and for specificity between
      subtypes.

PMID- 17434780
TI  - A rational strategy for a malarial vaccine development.
AB  - Twenty years ago we reported the first synthetic peptide-based anti-malarial
      vaccine named SPf66, which conferred limited protective efficacy in large-scale
      human field-trials. Our efforts towards a second vaccine generation based on the
      rational selection of conserved high activity binding peptides (HABPs) whose
      critical binding residues have to be precisely replaced by others. Introducing
      peptide bond isosters on these HABPs' critical binding residues constitutes also
      an important approach. Our results suggest that knowing a parasite's
      immunologically active peptides, their 3D structure, and their interaction for
      properly stabilizing MHC-II peptide-TCR complexes constitutes the basis for
      rationally designing a fully effective, multi-component, multistage subunit-based
      anti-malarial vaccine.

PMID- 17434781
TI  - [Antibiotics at term. Questions about five severe allergic accidents].
AB  - We recently observed five cases of severe maternal allergic accident due to the
      administration of antibiotics near or at term in order to treat or prevent Early
      Onset Neonatal Group B Streptococcal Sepsis. We discuss the treatment of a severe
      maternal allergic reaction and these dramatic observations make us wonder about a
      reasonable use of antibiotics.

PMID- 17434782
TI  - Ultrasound promoted ZrCl(4) catalyzed rapid synthesis of substituted 1,2,3,4
      tetrahydropyrimidine-2-ones in solvent or dry media.
AB  - Sonication of aromatic aldehydes, urea and ethyl acetoacetate in presence of
      solvent (ethyl alcohol) or solvent-less dry media (bentonite clay) supported
      zirconium (IV) chloride (ZrCl(4)) as catalyst at 35 kHz gives 6-methyl-4
      substitutedphenyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl
      esters proficiently in high yields.

PMID- 17434783
TI  - Ultrasonic inactivation of Bacillus alpha-amylase. I. effect of gas content and
      emitting face of probe.
AB  - Sonoinactivation of alpha-amylase from Bacillus amyloliquefacience was studied at
      a constant frequency of 30 kHz. The effect of sonotrode emitting face and gas
      content of medium on the efficiency of enzyme inactivation were investigated at
      different time-temperature combinations and generation of OH free radicals was
      also monitored. The results showed that ultrasound effectively inactivated alpha
      amylase with a minimum overall inactivation rate at 50 degrees C. The tip
      diameter of the sonotrode and the gas content of the medium both significantly
      affected the rate of enzyme inactivation. The increase of tip diameter increased
      the effect of ultrasound on the enzyme, while the removal of dissolved gas
      adversely influenced the cavitational events and reduced the rate of enzyme
      inactivation. Calculation of the kinetic and activation parameters revealed that
      ultrasound decreased the activation energy, E(a), activation enthalpy, DeltaH(#),
      and the activation Gibbs free energy, DeltaG(#), and strongly reduced the
      activation entropy, DeltaS(#), down to negative values. This huge reduction in
      activation entropy was attributed to the different mechanisms of inactivation
      induced by heat and ultrasound. It is proved in this study that ultrasonically
      generated OH free radicals and shear forces, which arise from pulsation- or
      collapse of bubbles, both can destabilize the enzyme, although their contribution
      to the overall inactivation varies depending on the temperature and the tip
      diameter of the sonotrode.

PMID- 17434784
TI  - Non-parametric geodesic active regions: method and evaluation for cerebral
      aneurysms segmentation in 3DRA and CTA.
AB  - Segmentation of vascular structures is a difficult and challenging task. In this
      article, we present an algorithm devised for the segmentation of such structures.
      Our technique consists in a geometric deformable model with associated energy
      functional that incorporates high-order multiscale features in a non-parametric
      statistical framework. Although the proposed segmentation method is generic, it
      has been applied to the segmentation of cerebral aneurysms in 3DRA and CTA. An
      evaluation study over 10 clinical datasets indicate that the segmentations
      obtained by our method present a high overlap index with respect to the ground
      truth (91.13% and 73.31%, respectively) and that the mean error distance from the
      surface to the ground truth is close to the in-plane resolution (0.40 and 0.38
      mm, respectively). Besides, our technique favorably compares to other alternative
      techniques based on deformable models, namely parametric geodesic active regions
      and active contours without edges.

PMID- 17434785
TI  - Micronucleus rate of buccal mucosal epithelial cells in relation to oral hygiene
      and dental factors.
AB  - Carcinogenesis of squamous cell carcinomas in the upper aero-digestive tract
      (UADT) is a multi-stage process. Since 1937, micronuclei (MN) have been
      considered a marker for genome damage in the initiation stage. By help of the
      micronucleus test, carcinogenic exposure can be proven in the mucosa area of the
      UADT. The hypothesis to be tested was that individual oral hygiene and the dental
      status, respectively - just like alcohol and tobacco abuse - are associated with
      the micronucleus rate in cytological preparations of the buccal mucosa. In a
      prospective clinical observation study, we determined in 100 probands the
      micronucleus frequency per 1000 mucosa epithelial cells. Study participants with
      a high number of missing teeth (M/T index, p=0.037), a below-average papillary
      bleeding index (PBI, p=0.032) and periodontal status, respectively (PSI, p=0.042)
      possessed a higher micronucleus number in comparison with restored dental
      conditions. Probands with composite restorations displayed a higher MN rate
      (p=0.006) compared to those with amalgam. However, we could not detect any
      significant relation with the prosthetic status (p> or =0.075). An adjustment was
      made according to alcohol and tobacco. We therefore conclude that subgingival
      plaque and synthetic dental materials in addition to chronic alcohol and tobacco
      consumption might have genotoxic relevance in the oral cavity.

PMID- 17434786
TI  - Plants need their vitamins too.
AB  - Over recent years, the pathways for the biosynthesis of many vitamins have been
      elucidated at the molecular level in plants, and several unique features are
      emerging. One is that the mitochondrion plays an important role in the synthesis
      of folate (vitamin B9), biotin (B7), pantothenate (B5), ascorbate (C), and
      possibly thiamin (B1). Second, the production of some of these cofactors is
      regulated by developmental cues, and perhaps more surprisingly, by environmental
      signals such as high light and salinity. Moreover, the biosynthesis of thiamin in
      Arabidopsis may be negatively regulated by a riboswitch, a novel method of gene
      regulation that is characteristic of cofactor biosynthesis in bacteria. Vitamin
      B12 is unique in that it is not found in vascular plants, but is abundant in
      algae; recent molecular work has revealed that algae do not synthesise the
      vitamin but instead obtain it from bacteria.

PMID- 17434787
TI  - Beta-oxidation in fatty acid degradation and beyond.
AB  - The degradation of fatty acids in plants occurs primarily in the peroxisomes
      through the beta-oxidation cycle. Enzymes that are involved in various aspects of
      beta-oxidation have been identified recently and shown to act biochemically on a
      diversity of fatty acids and derivatives. Analysis of several mutants has
      revealed essential roles for beta-oxidation in the breakdown of reserve
      triacylglycerols, seed development, seed germination and post-germinative growth
      before the establishment of photosynthesis. Beta-oxidation has also a
      considerable importance during the vegetative and reproductive growth phases, and
      plays a role in plant responses to stress, particularly in the synthesis of
      jasmonic acid.

PMID- 17434788
TI  - Engineering oilseeds for sustainable production of industrial and nutritional
      feedstocks: solving bottlenecks in fatty acid flux.
AB  - Oilseeds provide a unique platform for the production of high-value fatty acids
      that can replace non-sustainable petroleum and oceanic sources of specialty
      chemicals and aquaculture feed. However, recent efforts to engineer the seeds of
      crop and model plant species to produce new types of fatty acids, including
      hydroxy and conjugated fatty acids for industrial uses and long-chain omega-3
      polyunsaturated fatty acids for farmed fish feed, have met with only modest
      success. The collective results from these studies point to metabolic
      'bottlenecks' in the engineered plant seeds that substantially limit the
      efficient or selective flux of unusual fatty acids between different substrate
      pools and ultimately into storage triacylglycerol. Evidence is emerging that
      diacylglycerol acyltransferase 2, which catalyzes the final step in
      triacylglycerol assembly, is an important contributor to the synthesis of unusual
      fatty acid-containing oils, and is likely to be a key target for future oilseed
      metabolic engineering efforts.

PMID- 17434789
TI  - Trehalose 6-phosphate.
AB  - Trehalose 6-phosphate (T6P) is a sugar signal of emerging significance. It is an
      essential component of the mechanisms that coordinate metabolism with plant
      growth adaptation and development. Its significance began to dawn when genetic
      modification of the trehalose pathway produced dramatic phenotypes, before the
      genetic proliferation of the trehalose pathway in plants was fully realised. T6P
      regulates sugar utilization and starch metabolism and interacts with other
      signalling pathways, including those mediated by plant hormones. Trehalose
      phosphate synthases (TPSs) and trehalose phosphate phosphatases are regulated at
      the gene level by sugars, nitrate, cytokinin and abscisic acid. TPSs are also
      regulated post-translationally. Mechanistic details of how T6P signals are
      emerging, but still sparse. Nevertheless, even at this stage, targeting central
      regulators such as T6P offers promise in crop improvement.

PMID- 17434790
TI  - Suberin--a biopolyester forming apoplastic plant interfaces.
AB  - Suberized cell walls form physiologically important plant-environment interfaces
      because they act as barriers that limit water and nutrient transport and protect
      plants from invasion by pathogens. Plants respond to environmental stimuli by
      modifying the degree of suberization in root cell walls. Salt stress or drought
      induced suberization leads to a decrease in radial water transport in roots.
      Although reinforced, suberized cell walls never act as absolutely impermeable
      barriers. Deeper insights into the structure and biosynthesis of suberin are
      required to elucidate what determines the barrier properties. Progress has been
      obtained from analytical methods that enabled the structural characterization of
      oligomeric building blocks in suberin, and from the opening of suberin research
      to molecular genetic approaches by the elucidation of the chemical composition
      and tissue distribution of suberin in the model species Arabidopsis.

PMID- 17434791
TI  - Iron utilization and metabolism in plants.
AB  - The solubilization and long-distance allocation of iron between organs and
      tissues, as well as its subcellular compartmentalization and remobilization,
      involve various chelation and oxidation/reduction steps, transport activities and
      association with soluble proteins that store and buffer this metal. Maintaining
      iron homeostasis is an important determinant in building prosthetic groups such
      as heme and Fe-S clusters, and in assembling them into apoproteins, which are
      major components of plant metabolism. Such processes require complex protein
      machineries located in mitochondria and plastids. An essential role for iron
      metabolism and utilization in plant productivity is evidenced by the strong iron
      requirement for proper photosynthetic reactions.

PMID- 17434792
TI  - Tocopherol functions in photosynthetic organisms.
AB  - During the past decade, the genes required for tocopherol (vitamin E) synthesis
      in plants and cyanobacteria have been identified. A series of mutants in which
      specific pathway steps are disrupted have been generated, providing new insights
      into tocopherol functions in photosynthetic organisms. Tocopherols are essential
      for controlling non-enzymatic lipid peroxidation during seed dormancy and
      seedling germination. Their absence results in elevated levels of malondialdehyde
      and phytoprostanes, and in inappropriate activation of plant defense responses.
      Surprisingly, tocopherol deficiency in mature leaves has limited consequences
      under most abiotic stresses, including high intensity light stress. The cell wall
      development of phloem transfer cells under cold conditions is, however, severely
      impaired in mature leaves of tocopherol-deficient mutants, indicating that
      tocopherols are required for proper adaptation of phloem loading at low
      temperatures.

PMID- 17434793
TI  - The complex network of non-cellulosic carbohydrate metabolism.
AB  - Partitioning of carbon dominates intracellular fluxes in both photosynthetic and
      heterotrophic plant tissues, and has vast influence on both plant growth and
      development. Recently, much progress has been made in elucidating the structures
      of the biosynthetic and degradative pathways that link the major and minor pools
      of soluble carbohydrates to cellular polymers such as starch, heteroglycans and
      fructans. In most cases, the regulatory properties of these pathways have been
      elucidated and the enzymes involved have been investigated using reverse genetics
      approaches. Although many of the results from these approaches were merely
      confirmatory, several of them were highly unexpected. The challenge ahead is to
      achieve better understanding of metabolic regulation at the network level in
      order to develop more rational strategies for metabolic engineering.

PMID- 17434794
TI  - In vitro micronucleus assay scored by flow cytometry provides a comprehensive
      evaluation of cytogenetic damage and cytotoxicity.
AB  - This laboratory has previously reported on the development of a flow cytometry
      based method for scoring in vitro micronuclei in mouse lymphoma (L5178Y) cells
      [S.L. Avlasevich, S.M. Bryce, S.E. Cairns, S.D. Dertinger, In vitro micronucleus
      scoring by flow cytometry: differential staining of micronuclei versus apoptotic
      and necrotic chromatin enhances assay reliability, Environ. Molec. Mutagen. 47
      (2006) 56-66]. With this method, necrotic and mid/late stage apoptotic cells are
      labeled with the fluorescent dye ethidium monoazide. Cells are then washed,
      stripped of their cytoplasmic membranes, and incubated with RNase plus a pan
      nucleic acid dye (SYTOX Green). This process provides a suspension of free nuclei
      and micronuclei that are differentially stained relative to chromatin associated
      with dead/dying cells. The current report extends this line of investigation to
      include the human cell line TK6. Additionally, methods are described that
      facilitate simultaneous quantitative analysis of cytotoxicity, perturbations to
      the cell cycle, and what we hypothesize is aneuploidization. This comprehensive
      cytogenetic damage assay was evaluated with the following diverse agents:
      etoposide, ionizing radiation, methyl methanesulfonate, vinblastine, ethanol, and
      staurosporine. Cells were harvested after 30h of continuous treatment (in the
      case of chemicals), or following graded doses of radiation up to 1Gy. Key
      findings include the following: (1) Significant discrepancies in top dose
      selection were found for five of the six agents studied when relative survival
      measurements were based on Coulter counting versus flow cytometry. (2) Both
      microscopy- and flow cytometry-based scoring methods detected dose-dependent
      micronucleus formation for the four genotoxic agents studied, whereas no
      significant increases were observed for the presumed non-genotoxicants ethanol
      and staurosporine when top dose selection was based on flow cytometric indices of
      cytotoxicity. (3) SYTOX and ethidium monoazide fluorescence signals conveyed cell
      cycle and cell death information, respectively, and appear to represent valuable
      aids for interpreting micronucleus data. (4) The frequency of hypodiploid nuclei
      increased in response to each of the genotoxic agents studied, but not following
      exposure to ethanol or staurosporine. Collectively, these results indicate that a
      comprehensive assessment of genotoxicity and other test article-induced
      toxicities can be acquired simultaneously using a simple two-color flow cytometry
      based technique.

PMID- 17434795
TI  - The diagnosis of malaria and identification of plasmodium species by polymerase
      chain reaction in Turkey.
AB  - More than half of the world's population is exposed to malaria in approximately
      100 countries. Rapid diagnosis and correct treatment of cases are the main
      objectives of control programs in malaria endemic areas. We have developed a PCR
      method to determine the presence of plasmodium DNA in blood. The method can also
      identify the species of the plasmodium by restriction enzyme analysis of the
      amplified product. We evaluated the performance of this method in the diagnosis
      of malaria suspected cases in Turkey by comparing to microscopy of the blood
      smears: blood samples were obtained from 114 patients with malaria symptoms,
      including fever and/or chills lasting for several days, before starting
      treatment. Thin and thick blood smears were prepared immediately in the region of
      specimen collection. After isolation of DNA from blood samples, DNA was amplified
      by PCR and digested by restriction enzyme AluI. The obtained fragments were
      analyzed by agarose gel electrophoresis. The number of parasites in the thick and
      thin smears of the blood samples was evaluated microscopically after staining by
      Giemsa and results were compared by PCR results. Among 114 plasmodium positive
      cases detected by microscopy, 100 were also detected by PCR. There were 14 false
      negatives and no false positive by PCR. Compared to microscopy, the sensitivity,
      specificity and Positive Predictive Value (PPV) of PCR were determined as 76%,
      100% and 100%, respectively.

PMID- 17434797
TI  - Pesticides and childhood cancer: an update.
AB  - OBJECTIVES: Epidemiological studies have reported associations between childhood
      cancer and either parental or child exposure to pesticides. Reviews have been
      published in 1997, 1998 and 2006 where the evidence was found suggestive but not
      conclusive. The present review is an extended update of the latter one. METHODS:
      The PubMed database was searched to identify published studies on this topic
      issued between 1998 and 2006. RESULTS: Thirty-six new studies have been
      identified for this review. Some cohort studies and the majority of the case
      control studies suggest an increased risk for the cancer types studied,
      associated with exposure to pesticides in at least one of a large variety of
      exposure categories. However, the evidence is conflicting with regard to cancer
      types as well as to causative factors across studies. The major shortcomings
      concern exposure assessment, where, e. g., "farming" is treated equal to
      "exposure to pesticides", disregarding other possible exposures, e.g., to
      biological or infectious agents, and hitherto unidentified lifestyle factors.
      Also, many exposure categories used, mainly in case-control studies, lack
      chemical or toxicological plausibility. In most studies exposures were
      categorized as "ever vs. never", with little regard of exposure intensity or
      duration. CONCLUSIONS: The available literature does not allow firm conclusions
      with regard to pesticides and any type of childhood cancer. But even if the
      reported associations were true, exposure to pesticides could not explain the
      vast majority of childhood cancer cases. Investing in the acquisition and
      critical review of exposure information appears to be the crucial step for causal
      assessment in future research. However, focusing on the presence of pesticides,
      and not asking the question why they were used, might mask relevant associations
      to other causative agents.

PMID- 17434798
TI  - Assessing and credentialing standards of care: the UK Clinical Negligence Scheme
      for Trusts (CNST, Maternity).
AB  - The Clinical Negligence Scheme for Trusts (CNST) provides NHS trusts with a set
      of risk management standards for maternity services. These standards are designed
      to act as a framework, bringing focus to the clinical risk management procedures
      adopted by maternity services, and to contribute to the development and
      implementation of clinical governance, thereby improving patient care. Both the
      Royal College of Obstetricians and Gynaecologists (RCOG) and the Royal College of
      Midwives (RCM) have endorsed the standards because of their potential to benefit
      clinical care. By improving clinical risk management procedures within maternity
      units, the standards are ultimately intended to reduce the level of clinical
      negligence claims. Assessments against the CNST Maternity Clinical Risk
      Management Standards are currently conducted by Det Norske Veritas Ltd (DNV) on
      behalf of the NHS Litigation Authority (NHSLA) to ensure that members'
      contributions reflect their standards of clinical risk management. Although the
      claims data have not been collected on a consistent basis and are too immature to
      provide conclusions in an area notorious for its long tail, it does indicate that
      there has been a fall in the number and cost of maternity claims as a percentage
      of total clinical negligence claims reported to the NHSLA since the inception of
      CNST. This chapter examines whether there is evidence that the standards have had
      a measurable effect on clinical negligence claims.

PMID- 17434796
TI  - Sterol transport in yeast and the oxysterol binding protein homologue (OSH)
      family.
AB  - Sterols such as cholesterol are a significant component of eukaryotic cellular
      membranes, and their unique physical properties influence a wide variety of
      membrane processes. It is known that the concentration of sterol within the
      membrane varies widely between organelles, and that the cell actively maintains
      this distribution through various transport processes. Vesicular pathways such as
      secretion or endocytosis may account for this traffic, but increasing evidence
      highlights the importance of nonvesicular routes as well. The structure of an
      oxysterol-binding protein homologue (OSH) in yeast (Osh4p/Kes1p) has recently
      been solved, identifying it as a sterol binding protein, and there is evidence
      consistent with the role of a cytoplasmic, nonvesicular sterol transporter. Yeast
      have seven such proteins, which appear to have distinct but overlapping functions
      with regard to maintaining intracellular sterol distribution and homeostasis.
      Control of sterol distribution can have far-reaching effects on membrane-related
      functions, and Osh proteins have been implicated in a variety of processes such
      as secretory vesicle budding from the Golgi and establishment of cell polarity.
      This review summarizes the current body of knowledge regarding this family and
      its potential functions, placing it in the context of known and hypothesized
      pathways of sterol transport in yeast.

PMID- 17434799
TI  - Definition and classification of abnormal vaginal flora.
AB  - Studying the vaginal microflora is not only fascinating, with many discoveries to
      be made, it is also a very practical way to help women get rid of bothersome and
      sometimes dangerous infections. Gram-stained vaginal preparations, Pap smears,
      specific cultures, and nucleic acid detection techniques can be used to diagnose
      the constituents of the vaginal flora, but in trained hands office-based
      microscopy of a fresh vaginal smear, preferably using a x400 magnification phase
      contrast microscope, allows almost every diagnosis and combination of diagnoses
      imaginable. In this chapter I will address the pros and cons of the tools that
      are in use to study vaginal flora, and discuss the different types of bacterial
      flora and the difficulties encountered in reaching the correct diagnosis of
      pathological conditions. The 'intermediate flora' is addressed separately, and a
      new entity--'aerobic vaginitis'--is discussed. Future research should focus on
      the interaction between infecting microorganisms and host defence mechanisms, as
      both together generate the pathogenicity of these conditions.

PMID- 17434800
TI  - Burn injury pain: the continuing challenge.
AB  - The development of more effective methods of relieving pain associated with burn
      injury is a major unmet medical need. Not only is acute burn injury pain a source
      of immense suffering, but it has been linked to debilitating chronic pain and
      stress-related disorders. Although pain management guidelines and protocols have
      been developed and implemented, unrelieved moderate-to-severe pain continues to
      be reported after burn injury. One reason for this is that the intensity of pain
      associated with wound care and rehabilitation therapy, the major source of severe
      pain in this patient population, varies widely over the 3 phases of burn
      recovery, making it difficult to estimate analgesic requirements. The effects of
      opioids, the most commonly administered analgesics for burn injury procedural
      pain, are difficult to gauge over the course of burn recovery because the need
      for an opioid may change rapidly, resulting in the overmedication or
      undermedication of burn-injured patients. Understanding the mechanisms that
      contribute to the intensity and variability of burn injury pain over time is
      crucial to its proper management. We provide an overview of the types of pain
      associated with a burn injury, describe how these different types of pain
      interfere with the phases of burn recovery, and summarize pharmacologic pain
      management strategies across the continuum of burn care. We conclude with a
      discussion and suggestions for improvement. Rational management, based on the
      underlying mechanisms that contribute to the intensity and variability of burn
      injury pain, is in its infancy. The paucity of information highlights the need
      for research that explores and advances the identification of mechanisms of acute
      and chronic burn injury pain. PERSPECTIVE: Researchers continue to report that
      burn pain is undertreated. This review examines burn injury pain management
      across the phases of burn recovery, emphasizing 3 types of pain that require
      separate assessment and management. It provides insights and suggestions for
      future research directions to address this significant clinical problem.

PMID- 17434801
TI  - Ketamine as an adjuvant for treatment of cancer pain in children and adolescents.
AB  - In children with advanced stages of cancer, pain control remains inadequate in
      many patients and a solution to this problem is sorely lacking. Factors related
      to progression of the primary disease and side-effects of high doses of opioids,
      the mainstay of pain therapy, contribute to the inadequacy of pain control. In
      addition, few studies suggest that opioids, by inducing tolerance, having
      pronociceptive effects and producing hyperalgesia in some patients, can also
      contribute to inadequacy of pain control. Researchers have shown that N-methyl-D
      aspartate (NMDA) receptor antagonists may have a role in mitigating opioid
      induced tolerance and hyperalgesia in adults. However, literature on NMDA
      antagonists to treat cancer pain in children and adolescents is scarce. We used
      subanesthetic doses of ketamine to treat 11 children and adolescents who were on
      high doses of opioids and yet had uncontrolled cancer pain. A low-dose ketamine
      infusion was administered to all patients to modulate the need for rapidly
      escalating opioid therapy. We found that in 8 of 11 patients, ketamine infusions
      used as an adjuvant to opioid analgesia was associated with opioid-sparing
      effects and apparent improvement in pain control and in the children's ability to
      interact with their family. This study suggests that infusions of ketamine may
      offer a promising therapeutic option in the treatment of appropriately selected
      children and adolescents with intractable cancer pain. PERSPECTIVE: In many
      children with advanced stages of cancer, pain control remains inadequate. We used
      subanesthetic doses of ketamine to treat 11 children and adolescents who were on
      high doses of opioids and had uncontrolled cancer pain. In the majority of
      patients, ketamine appeared to improve pain control and to have an opioid-sparing
      effect.

PMID- 17434802
TI  - Gastrocardiac afferent convergence in upper thoracic spinal neurons: a central
      mechanism of postprandial angina pectoris.
AB  - The aim of this study was to examine whether gastric afferent information
      converged onto upper thoracic spinal neurons that received noxious cardiac input.
      Extracellular potentials of single upper thoracic (T3) spinal neurons were
      recorded in pentobarbital-anesthetized, paralyzed, ventilated male rats. Gastric
      distension (GD) (20, 40, 60 mm Hg, 20 seconds) was produced by air inflation of a
      latex balloon surgically placed in the stomach. A catheter was placed in the
      pericardial sac to administer bradykinin solution (10 microg/mL, 0.2 mL, 1
      minute) as a noxious cardiac stimulus. Noxious GD (> or =40 mm Hg) altered
      activity of 26 of 31 (84%) spinal neurons receiving cardiac input. Twenty-two
      (85%) gastrocardiac convergent neurons were excited, and 1 neuron was inhibited
      by both intrapericardial bradykinin and GD; the remainder exhibited biphasic
      response patterns. Twenty-three of 26 (88%) gastrocardiac neurons also received
      convergent somatic input from the chest, triceps, and upper back areas. Bilateral
      cervical vagotomy did not significantly affect excitatory responses to GD in 5 of
      5 neurons tested. Spinal transection at the C1 segment after vagotomy did not
      affect excitatory responses to GD in 3 of 4 neurons but abolished the GD response
      in 1 neuron. These data showed that a gastric stimulus excited T3 spinal neurons
      with noxious cardiac input primarily by way of intraspinal ascending pathways.
      PERSPECTIVE: Convergence of gastric afferent input onto upper thoracic spinal
      neurons receiving noxious cardiac input that was observed in the present study
      may provide a spinal mechanism that explains stomach-heart cross-organ
      communication, such as postprandial triggering and worsening of angina pectoris
      in patients with coronary artery disease.

PMID- 17434803
TI  - Psychophysics, flare, and neurosecretory function in human pain models: capsaicin
      versus electrically evoked pain.
AB  - Intradermal capsaicin injection (CAP) and electrical current stimulation (ES) are
      analyzed in respect to patterns and test-retest reliability of pain as well as
      sensory and neurosecretory changes. In 10 healthy subjects, 2x CAP (50 microg)
      and 2x ES (5 to 30 mA) were applied to the volar forearm. The time period between
      2 identical stimulations was about 4 months. Pain ratings, areas of mechanical
      hyperalgesia, and allodynia were assessed. The intensity of sensory changes was
      quantified by using quantitative sensory testing. Neurogenic flare was assessed
      by using laser Doppler imaging. Calcitonin gene-related peptide (CGRP) release
      was quantified by dermal microdialysis in combination with an enzyme immunoassay.
      Time course and peak pain ratings were different between CAP and ES. Test-retest
      correlation was high (r > or = 0.73). Both models induced primary heat
      hyperalgesia and primary plus secondary pin-prick hyperalgesia. Allodynia
      occurred in about half of the subjects. Maximum flare sizes did not differ
      between CAP and ES, but flare intensities were higher for ES. Test-retest
      correlation was higher for flare sizes than for flare intensity. A significant
      CGRP release could only be measured after CAP. The different time courses of pain
      stimulation (CAP: rapidly decaying pain versus ES: pain plateau) led to different
      peripheral neurosecretory effects but induced similar central plasticity and
      hyperalgesia. PERSPECTIVE: The present study gives a detailed overview of
      psychophysical and neurosecretory characteristics induced by noxious stimulation
      with capsaicin and electrical current. We describe differences, similarities, and
      reproducibility of these human pain models. These data might help to interpret
      past and future results of human pain studies using experimental pain.

PMID- 17434804
TI  - Repetitive transcranial magnetic stimulation (rTMS) in experimentally induced and
      chronic neuropathic pain: a review.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is an emerging technology
      that has been demonstrated to be useful in the treatment of depression and
      potentially useful in the management of several neurologic conditions. More
      recently, increasing attention has been directed at evaluating its efficacy in
      the treatment of patients with chronic neuropathic pain. We first discuss the
      literature examining the efficacy of rTMS in trials of experimentally induced
      acute pain as well as among patients with chronic pain. Examining frequency data
      obtained from the available literature, we attempted to identify some of the
      parameters of rTMS that appear to be related to its analgesic effects. An
      overview of the mechanisms underlying its potential analgesic role is discussed;
      generally, the influences of rTMS on cortical, and, indirectly, subcortical,
      neurons may reduce pain transmission ascending from spinothalamic tracts, thereby
      mitigating pain. Finally, we discuss some of the methodological issues and
      limitations of available studies and offer recommendations for further research.
      PERSPECTIVE: The authors provide a comprehensive review of rTMS use in the
      treatment of neuropathic pain in the literature available to date. Although the
      clinical usefulness of rTMS in pain has, as yet, to be determined, it offers
      insights into the pathophysiologic processes involved in the maintenance and
      exacerbation of chronic pain.

PMID- 17434805
TI  - Polyostotic fibrous dysplasia of the cervical spine: case report and review of
      the literature.
AB  - BACKGROUND CONTEXT: Multiple lytic lesions of the spine usually represent
      metastatic or infectious disease processes. PURPOSE: To describe an extremely
      rare presentation of an uncommon disease process. STUDY DESIGN/SETTING: Case
      report/university hospital. METHODS: We describe the management of a patient who
      presented with a pathological fracture of C3 and multiple lytic lesions of the
      cervical spine. RESULTS: After reconstructive surgery, the final pathological
      diagnosis was fibrous dysplasia. CONCLUSION: Fibrous dysplasia is rarely seen in
      the cervical spine and may mimic other pathological processes. The surgical and
      medical management of spinal fibrous dysplasia is described.

PMID- 17434806
TI  - Intrathecal migratory foreign body without neurological deficit after a gunshot
      wound.
AB  - BACKGROUND CONTEXT: Penetrating bullets dissipate thermal and kinetic energy into
      surrounding tissues. Within the thecal sac, this is universally associated with
      neurological deficits. PURPOSE: We report a case of intrathecal penetration of a
      bullet without neurological deficit. STUDY DESIGN: Case report. METHODS: A 14
      year-old girl was shot in the back, entering adjacent to the L3 vertebra and
      settling within the spinal canal adjacent to the S1 vertebra. In the absence of
      neurological deficits, initial management was nonoperative. RESULTS: Over the
      period of a week, the patient developed an episode of intense radicular pain,
      although her neurological examination remained normal. Location of the bullet was
      shown to vary from S1 to T12 on multiple imaging studies, and this was influenced
      by patient positioning. She subsequently underwent a bilateral hemilaminotomy and
      durotomy with excision of the intrathecal bullet. CONCLUSIONS: Patients can avoid
      neurological injury even with an intrathecal gunshot wound. However, intrathecal
      bullets may then migrate and cause variable neurological complaints,
      necessitating surgical removal. Patient positioning can influence bullet location
      which can be useful in surgical planning.

PMID- 17434807
TI  - Clinical management for spontaneous spinal epidural hematoma: diagnosis and
      treatment.
AB  - BACKGROUND CONTEXT: Spontaneous spinal epidural hematoma (SSEH) is a very rare
      condition, so there were few studies assessing the management criteria of SSEH.
      PURPOSE: To assess the differential diagnosis and clinical results of treatment
      for SSEH. STUDY DESIGN: A retrospective chart and radiograph review of the
      patients with SSEH. PATIENT SAMPLE: Seven consecutive patients with SSEH who were
      treated in our institute. OUTCOME MEASURES: Differential diagnosis, severity of
      the paresis, and treatment selection were assessed preoperatively and
      postoperatively. METHODS: We assessed the relationship between the following
      parameters and clinical results: (1) the initial symptoms, (2) imaging diagnosis
      of magnetic resonance imaging (MRI), (3) treatment selection (conservative or
      surgical treatment), (4) the interval of surgery, and (5) the severity of paresis
      using ASIA impairment scale (AIS) grading. RESULTS: In all patients, the symptoms
      at onset were severe neck and back pain. MRI showed isointensity to the spinal
      cord in the T1-weighted view and iso- or high intensity in the T2-weighted view.
      A solid pattern in MRI was shown in 4 patients, and a mosaic pattern was shown in
      3 patients. Decompression was performed in five cases, and spontaneous recovery
      appeared in two cases. The mean interval time for operation was 29.8 hours. The
      severity of paresis was grade B in 3 cases and grade C in 4 cases at onset. These
      cases recovered to become grade E in 3 cases and grade D in 4 cases. Neurological
      deficits were present in two patients with conservative therapy and in two
      patients with a long interval for operation. CONCLUSIONS: Precise diagnosis
      without delay and rapid surgical treatment are essential for the management of
      SSEH.

PMID- 17434808
TI  - Conservative treatment of an atlantoaxial degenerative articular cyst: case
      report.
AB  - BACKGROUND: Atlantoaxial degenerative articular cysts are rare lesions that can
      cause extradural compression of the cervicomedullary junction. When symptomatic,
      they usually require surgical treatment. We report an unusual case of spontaneous
      regression of an atlantoaxial degenerative articular cyst after conservative
      treatment with an external cervical brace along with a systemic therapy with
      nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids. We also discuss the
      potential pathogenetic mechanisms involved. PURPOSE: To describe a case of
      significant volume reduction of an atlantoaxial articular degenerative cyst in a
      patient treated with a Philadelphia collar and anti-inflammatory drugs. STUDY
      DESIGN: Case report with analysis of the literature. METHODS: A 80-year-old
      patient was admitted to our institution with a history of progressive
      tetraparesis, ataxic gait, and cervical pain. A cervical spine magnetic resonance
      imaging (MRI) scan showed an extradural mass lesion behind the dens of C2 causing
      significant compression of the cervicomedullary junction, suggesting the
      diagnosis of atlantoaxial degenerative articular cyst. The patient refused
      surgery in favour of a conservative treatment with a Philadelphia collar and a
      short-term course of NSAIDs and corticosteroids. RESULTS: After 6 weeks, the
      patient's neurological condition improved, and a 6-month follow-up cervical spine
      MRI scan revealed an almost complete regression of the atlantoaxial cystic
      lesion. At a 1-year follow-up, his clinical condition was further improved.
      CONCLUSIONS: Atlantoaxial articular degenerative cysts are rare lesions that
      should be included in the differential diagnosis of those extradural lesions that
      can cause a ventral or ventrolateral compression of the cervicomedullary
      junction. They most commonly occur in elderly female patients affected by diffuse
      arthrosic degeneration of the cervical spine, with or without clear radiological
      signs of atlantoaxial instability, and have a typical appearance on MRI imaging.
      Surgery, with direct excision of the cyst and/or a C1-C2 fusion, is the first
      treatment of choice. Nevertheless, our report points out the possibility of a
      significant spontaneous regression of these lesions following a simple
      conservative strategy based on the use of an external cervical brace together
      with a systemic anti-inflammatory therapy.

PMID- 17434810
TI  - Bioinsecticidal activity of Archidendron ellipticum trypsin inhibitor on growth
      and serine digestive enzymes during larval development of Spodoptera litura.
AB  - The roles of serine proteases involved in the digestion mechanism of the cutworm
      Spodoptera litura (Lepidoptera: Noctuidae) were examined (in vitro and in vivo)
      following feeding of plant protease inhibitors. A trypsin inhibitor from
      Archidendron ellipticum (AeTI) was purified by ammonium sulfate fractionation,
      ion-exchange chromatography and size-exclusion chromatography (HPLC) and its
      bioinsecticidal properties against S. litura were compared with Soybean Kunitz
      trypsin inhibitor (SBTI). AeTI inhibited the trypsin-like activities of the
      midgut proteases of fifth instar larvae of S. litura by over 70%. Dixon plot
      analysis revealed competitive inhibition of larval midgut trypsin and
      chymotrypsin by AeTI, with an inhibition constant (K(i)) of 3.5x10(-9) M and
      1.5x10(-9) M, respectively. However, inhibitor kinetics using double reciprocal
      plots for both trypsin and chymotrypsin inhibitions demonstrated a mixed
      inhibition pattern. Feeding experiments conducted on different (neonate to
      ultimate) instars suggested a dose-dependent decrease for both the larval body
      weight as well as % survival of larva fed on diet containing 50, 100 and 150
      microM AeTI. Influence of AeTI on the larval gut physiology indicated a 7-fold
      decrease of trypsin-like protease activity and a 5-fold increase of chymotrypsin
      like protease activity, after being fed with a diet supplemented with 150 microM
      AeTI. This study suggests that although the early (1st to 3rd) larval instars of
      S. litura are susceptible to the trypsin inhibitory action of AeTI, the later
      instars may facilitate the development of new serine proteases, insensitive to
      the inhibitor.

PMID- 17434809
TI  - Atlantoaxial fusion: a biomechanical analysis of two C1-C2 fusion techniques.
AB  - BACKGROUND CONTEXT: Different atlantoaxial fusion techniques are used for
      instability. Transarticular screws are biomechanically superior to wiring
      techniques and equivalent to C1 lateral mass to C2 pedicle (C1LM-C2P) fixation.
      Recently, C1 lateral mass to C2 laminar (C1LM-C2L) fixation has been shown to
      have flexibility similar to C1LM-C2P fixation in flexion, extension, lateral
      bending, and axial rotation. PURPOSE: Compare the stiffness of C1LM-C2P with C1LM
      C2L screw rod fixation. STUDY DESIGN: In vitro biomechanical study. OUTCOME
      MEASURES: Stiffness in flexion/extension, lateral bending, axial rotation, and
      anterior-posterior (AP) translation. METHODS: Eight fresh-frozen human cadaveric
      cervical spines (C1-C3) were tested intact and, after a type II odontoid
      fracture, were instrumented and tested with two fixation constructs: C1LM-C2P
      screws and C1LM-C2L screws. The testing involved flexion, extension, lateral
      bending, AP translation, and axial rotation. Stiffness was measured and compared
      with a repeated-measures analysis. RESULTS: C1LM-C2P was significantly stiffer
      than the intact in AP translation (p<.001), lateral bending (p=.001), and axial
      rotation (p=.002) and equivalent in flexion/extension (p=.09). C1LM-C2L was
      significantly stiffer than the intact in AP translation (p<.01) and axial
      rotation (p<.004) and equivalent in lateral bending (p<.71) and flexion/extension
      (p=.22). C1LM-C2P was stiffer than C1LM-C2L in right/left lateral bending
      (p<.001) and axial rotation (p=.009) and equivalent in AP translation (p=.06) and
      flexion/extension (p=.74). CONCLUSION: C1LM-C2P fixation is equivalent to C1LM
      C2L fixation in flexion/extension and AP translation and superior in lateral
      bending and axial rotation.

PMID- 17434811
TI  - The field representation language.
AB  - The complexity of quantitative biomedical models, and the rate at which they are
      published, is increasing to a point where managing the information has become all
      but impossible without automation. International efforts are underway to
      standardise representation languages for a number of mathematical entities that
      represent a wide variety of physiological systems. This paper presents the Field
      Representation Language (FRL), a portable representation of values that change
      over space and/or time. FRL is an extensible mark-up language (XML) derivative
      with support for large numeric data sets in Hierarchical Data Format version 5
      (HDF5). Components of FRL can be reused through unified resource identifiers
      (URI) that point to external resources such as custom basis functions, boundary
      geometries and numerical data. To demonstrate the use of FRL as an interchange we
      present three models that study hyperthermia cancer treatment: a fractal model of
      liver tumour microvasculature; a probabilistic model simulating the deposition of
      magnetic microspheres throughout it; and a finite element model of hyperthermic
      treatment. The microsphere distribution field was used to compute the heat
      generation rate field around the tumour. We used FRL to convey results from the
      microsphere simulation to the treatment model. FRL facilitated the conversion of
      the coordinate systems and approximated the integral over regions of the
      microsphere deposition field.

PMID- 17434812
TI  - Decision-making and breast cancer clinical trials: how experience challenges
      attitudes.
AB  - OBJECTIVE: The aim of this study was to measure women's preferences about
      decision-making and their impact to participate or not to a hypothetical
      randomised controlled trial (RCT). METHODS: We surveyed prospectively breast
      cancer patients invited to participate in a clinical RCT (group 1a=201
      acceptances, group 1b=66 refusals) or not invited (group 2=188). All women had
      the same treatment. RESULTS: Decision-making preferences of patients who had
      refused clinical RCT entry were more patient's centred (72.3%) compared to those
      of patients who accepted (35.0%, P<0.001). Altruism was not a significant
      determinant of patients' participation. Randomisation was considered acceptable
      in 52.0% (group 1a) compared to 16.9% and 21.1% for group 1b or group 2,
      respectively (P<0.001). It was the main predictor of willingness to participate
      in a hypothetical RCT (adjusted odds ratio (OR(adj)) 4.6; 95% confidence interval
      [2.7-7.7]; P<0.001) with the patient group allocation (OR(adj) group 1a=5.0 [2.9
      8.7]; group 1b=0.2 [0.0-0.8]; group 2=1 [referent]; P<0.001). After multivariate
      adjustment, willingness to participate was also significantly related with
      medical decision-making preferences (OR(adj) 2.2 [1.0-4.9]; P=0.045), with the
      feeling of being unable to refuse a doctor's proposal (OR(adj) 1.8 [1.1-3.2];
      P=0.031), and with satisfaction with doctors' communication (OR(adj) 3.1 [1.5
      7.8]; P<0.001). CONCLUSIONS: Patients' acceptance to participate in a RCT is
      preferred to be doctor's decision, whereas refusal is a personal one. When
      proposing a RCT, doctors must deal with patients' a priori negative feelings
      about randomisation. They should thoroughly discuss the reasons for and
      importance of randomisation as well as the other aspects of participating in the
      trial in order to give patients all of the information they need to make an
      informed decision.

PMID- 17434813
TI  - Industry-sponsored research in developing countries.
AB  - BACKGROUND: Industry has become an important source of funding for clinical
      research; guidelines governing the relationship between industry and medical
      institutions are not clear in developing countries and hence we wanted to test
      attitudes and practices in those countries and compare them to developed
      countries. We conducted a survey amongst medical practitioners in developed and
      Arab countries representing developing countries, in order to document their
      views towards industry-sponsored research and their actual practice in this
      regard. METHODS: A structured questionnaire was distributed by email, mail and
      through personal contacts. The questionnaire included information on
      characteristics of the practitioners involved, their attitudes towards industry
      sponsored research and their actual practices. The questionnaire was distributed
      to 510 medical practitioners of countries in both groups. Practitioners
      representing developed countries were from the United States, United Kingdom,
      Australia and New Zealand. Those representing developing countries included Arab
      countries from Asia and Africa. RESULTS: We found that there were contrasting
      views and practices between the two groups although more than 80% in both groups
      agreed that industry-sponsored research is necessary. 69.7% of respondents in
      developed countries participated in industry-sponsored research while only 30.1%
      did so in developing countries. Guidelines governing such research were better
      adhered to in developed countries than in developing countries. Where there were
      no authors who were not part of investigators in developed countries, 16.3% of
      industry-sponsored research in developing countries included authors who were not
      part of the investigators. Research ethics committees were present in 94% and 58%
      of institutions in developed and developing countries respectively. Review bodies
      were available in 57% and 41% in developed and developing countries. CONCLUSIONS:
      Industry-sponsored research is necessary; it is much more common in developed
      countries. Clear guidelines governing industry-sponsored research should be
      adopted in developing countries, including the establishment of research ethics
      committees and review bodies to monitor such research.

PMID- 17434814
TI  - Group sequential t-test for clinical trials with small sample sizes across
      stages.
AB  - Interim analyses are often applied in clinical trials for various reasons. To
      assess the effect of a clinical treatment, the group sequential t-test with a
      fixed number of interim analyses is frequently used in clinical trials. The
      existing critical values used in group sequential t-tests are obtained from
      normal approximations of t-statistics. In practice, however, normal approximation
      is not accurate when some sample sizes of treatment arms in some stages are
      small. In this paper, instead of using normal approximation, we directly obtain
      the critical values via a Monte Carlo method. We list some critical values for
      certain sample sizes and number of interim analyses, and provide some SAS code
      for general situations. We also consider the sample size calculation and run some
      simulations to check the accuracy of our critical values. The simulation results
      show that our critical values yield type I error probabilities that are very
      close to the nominal significance level, whereas the existing critical values
      based on normal approximation are not accurate when some sample sizes are small
      across stages.

PMID- 17434815
TI  - Adhesive strength and curing rate of marine mussel protein extracts on porcine
      small intestinal submucosa.
AB  - An adhesive protein extracted from marine mussels (Mytilus edulis) was used to
      bond strips of connective tissue for the purpose of evaluating the use of curing
      agents to improve adhesive curing. Specifically, mussel adhesive protein solution
      (MAPS, 0.5mM dihydroxyphenylalanine) was applied, with or without the curing
      agents, to the ends of two overlapping strips of porcine small intestinal
      submucosa (SIS). The bond strength of this lap joint was determined after curing
      for 1h at room temperature (25 degrees C). The strength of joints formed using
      only MAPS or with only the ethyl, butyl or octyl cyanoacrylate adhesives were
      determined. Although joints bonded using ethyl cyanoacrylate were strongest,
      those using MAPS were stronger than those using butyl and octyl cyanoacrylates.
      The addition of 25mM solutions of the transition metal ions V5+, Fe3+ and Cr6+,
      which are all oxidants, increased the bond strength of the MAPS joints. The V5+
      gave the strongest bonds and the Fe3+ the second strongest. In subsequent tests
      with V5+ and Fe3+ solutions, the bond strength increased with V5+ concentration,
      but it did not increase with Fe3+ concentration. Addition of 250mM V5+ gave a
      very strong bond.

PMID- 17434816
TI  - Arterial embolisation to control haemorrhage following colonoscopic polypectomy.

PMID- 17434817
TI  - Evidences for a role of p38 MAP kinase in the stimulation of alkaline phosphatase
      and matrix mineralization induced by parathyroid hormone in osteoblastic cells.
AB  - Increased bone formation by PTH mainly results from activation of osteoblasts, an
      effect largely mediated by the cAMP-PKA pathway. Other pathways, however, are
      likely to be involved in this process. In this study we investigated whether PTH
      can activate p38 MAPK and the role of this kinase in osteoblastic cells. Bovine
      PTH(1-34) and forskolin markedly increased alkaline phosphatase (ALP) activity
      and doubled osteocalcin (Oc) expression in early differentiating MC3T3-E1 cells.
      These effects were associated with increase in cellular cAMP and activation of
      the MAP kinases ERK and p38. Activation of these MAP kinases was detectable after
      1 h incubation with 10(-7) M PTH and lasted 1-2 h. Activation of p38 was mimicked
      by 10 microM forskolin and prevented by H89 suggesting a cAMP-PKA-dependent
      mechanism of p38 activation. Interestingly, PTH-induced ALP stimulation was dose
      dependently inhibited by a specific p38 inhibitor with no change in the
      generation of cAMP and the production of osteocalcin. Similar inhibitory effect
      was obtained in cells stably expressing a dominant-negative p38 molecule.
      Finally, treatment of MC3T3-E1 cells with PTH for 3 weeks significantly enhanced
      matrix mineralization and this effect was markedly reduced by a selective p38 but
      not a specific MEK inhibitor. In conclusion, data presented in this study
      indicate that PTH can activate p38 in early differentiating osteoblastic cells.
      Activation of p38 is cAMP-PKA-dependent and mediates PTH-induced stimulation of
      ALP which plays a critical role for the calcification of the bone matrix.

PMID- 17434818
TI  - Adjuvant treatment of colon cancer: past, present and future.
AB  - This manuscript summarizes recent progress in the adjuvant treatment of colon
      cancer. 5-Fluorouracil plus leucovorin, that have been considered standard
      therapy over the last 15 years, have now been replaced by combination
      chemotherapy, at least in stage III disease. The treatment of stage II disease is
      still somewhat less established. Prognostic and predictive biological markers are
      urgently needed for further fine-tuning of therapy. Molecular targeted agents
      have been developed with proven activity in advanced disease and are now being
      assessed in the adjuvant setting. It is expected that the inclusion of these new
      agents will lead to a further enhancement of treatment outcome. Those involved in
      the treatment of colorectal cancer should be encouraged to continue to provide
      optimal patient care and to participate in clinical trials in order to increase
      the evidence on which they can base their clinical judgement and to make further
      progress.

PMID- 17434819
TI  - In vitro selection and characterization of mutants in TEM-1-producing Escherichia
      coli by ceftazidime and ceftibuten.
AB  - The present work was undertaken to study the ability of ceftazidime and
      ceftibuten to selectin vitro Escherichia coli HB101 harboring bla(TEM-1) beta
      lactamase gene. Minimum inhibitory concentrations (MICs) of ceftazidime and
      ceftibuten were increased by a factor of 32, overcoming in the case of
      ceftazidime the breakpoint for clinical resistance. Outer membrane protein
      analysis and PCR for bla(TEM )alleles revealed that ceftazidime and ceftibuten
      select for different resistance mechanisms. Ceftazidime created mutants that
      encode an extended-spectrum beta-lactamase (TEM-12) and exhibit decreased
      expression of OmpF. Ceftibuten was unable to select for extended-spectrum beta
      lactamase expressing mutants but reduced the expression of two porins, OmpC and
      OmpF. The stability of ceftibuten to hydrolysis and the difference in the
      structure of these beta-lactam antibiotics could be responsible for the selection
      of different mechanisms of resistance.

PMID- 17434820
TI  - Sensitivity and specificity of various beta-lactam antibiotics and phenotypical
      methods for detection of TEM, SHV and CTX-M extended-spectrum beta-lactamases.
AB  - The aim of this study was to compare the sensitivity and specificity of six
      different beta-lactam antibiotics using five phenotypical tests for detection of
      extended spectrum beta-lactamases (ESBLs) based on synergism of beta-lactam
      antibiotics and clavulanate. Experiments were performed on a set of 80 Klebsiella
      pneumoniae strains and 105 Escherichia coli strains with previously characterized
      ESBLs (SHV, TEM and CTX-M). ESBLs were detected by five different phenotypical
      methods: MIC (minimum inhibitory concentration) determination of beta-lactam
      antibiotics with and without clavulanate, double-disk synergy test (DDST),
      inhibitor-potentiated disk-diffusion test (IPDDT), CLSI-Clinical and Laboratory
      Standard Institution (former NCCLS) combined-disk-test, and modified MAST-disk
      diffusion test (MAST-DD-test). Seven antibiotics were tested as indicators of
      ESBL production: ceftazidime, cefotaxime, ceftriaxone, aztreonam, ceftibuten,
      cefpodoxime and cefepime. Ceftazidime and aztreonam were the best indicators for
      SHV-5, SHV-12 and TEM beta-lactamases whereas cefotaxime and ceftriaxone were the
      most sensitive in detection of SHV-2 and CTX-M beta-lactamases in DDST, IPDDT and
      CLSI test. MIC determination of beta-lactam antibiotics with and without
      clavulanate was the most sensitive method. DDST was the least sensitive test.
      Double-disk synergy test, which is the most frequently used test for detection of
      ESBLs in routine laboratories, was the least sensitive independently of the
      indicator antibiotic. Since MIC determination is a very laborious and time
      consuming method, we would recommend the NCCLS combined disk test or IPDD test
      for detection of ESBLs in routine laboratories with 5 mm zone augmentation
      breakpoint.

PMID- 17434821
TI  - Widespread detection of VEB-1-type extended-spectrum beta-lactamases among
      nosocomial ceftazidime-resistant Pseudomonas aeruginosa isolates in Sofia,
      Bulgaria.
AB  - A total of 132 ceftazidime-resistant clinical isolates of Pseudomonas aeruginosa
      were collected during 2001-2005 from 5 university hospitals in Sofia, Bulgaria to
      assess the current levels of antimicrobial susceptibility and to evaluate
      resistance mechanisms to beta-lactams. Antimicrobial susceptibilities were
      detected by a disk diffusion method and E-test. Polymerase chain reaction
      amplification and sequencing of bla(VEB-1 )and bla(PER-1 )were performed. The
      antibiotic resistance rates were: to piperacillin 90.2%, piperacillin/tazobactam
      52.3%, ceftazidime 94.7%, cefepime 88.6%, cefpirome 98.5%, aztreonam 85.6%,
      imipenem 66.6%, meropenem 63.6%, amikacin 81.1%, gentamicin 84.8%, tobramycin
      89.4%, netilmicin 57.6%, ciprofloxacin 83.4%. Structural genes for VEB-1 extended
      spectrum beta -lactamases (ESBLs) were found in 75 (56.8%) of the isolates. PER-1
      ESBLs were not detected. The VEB-1-producing strains were more resistant than VEB
      1 non-producers to amikacin, gentamicin, tobramycin and ciprofloxacin ( P<0.001).
      VEB-1 appears to have a significant presence among ceftazidime-resistant P.
      aeruginosa isolates from Sofia.

PMID- 17434822
TI  - Antimicrobial efficacy of gatifloxacin and moxifloxacin with and without
      benzalkonium chloride compared with ciprofloxacin and levofloxacin against
      methicillin-resistant Staphylococcus aureus.
AB  - We compared the antimicrobial activity of gatifloxacin and moxifloxacin with and
      without benzalkonium chloride (BAK) against clinical isolates of methicillin
      resistant Staphylococcus aureus (MRSA). Minimum inhibitory concentrations (MICs)
      against clinical isolates of MRSA were evaluated. Approximately 10(5 )CFU/ml of
      methicillinresistant S. aureus was added to Mueller-Hinton broth containing two
      fold concentration increments of drug. For the evaluation of gatifloxacin with
      BAK, 50 microg/ml of BAK were added to the first well of the plate with
      gatifloxacin or moxifloxacin and then serially diluted. The combination of
      gatifloxacin or moxifloxacin with BAK was more active than either fluoroquinolone
      without BAK. The MICs ranged from <or=0.008 microg/ml to 0.125 microg/ml for
      gatifloxacin plus BAK, from 0.063 microg/ml to (3)8 microg/ml with unpreserved
      gatifloxacin from <0.004 to 0.25 for moxifloxacin plus BAK, and from <or=0.016
      microg/ml to 16.0 microg/ml with unpreserved moxifloxacin. The combinations of
      gatifloxacin or moxifloxacin and BAK were highly active against MRSA in vitro,
      providing MICs that were approximately 2- to 500-fold lower than the MICs
      provided by either gatifloxacin or moxifloxacin without BAK.

PMID- 17434824
TI  - Increasing resistance according to patient's age and sex in Escherichia coli
      isolated from urine in Italy.
AB  - The prevalence of Escherichia coli among the uropathogens routinely isolated in
      non-hospital laboratories (Labs) and its susceptibility profiles were
      investigated. Thirty-three Labs were selected throughout Italy. In vitro assays
      were performed by means of disk diffusion according to the CLSI. Females were
      prevalent (79.9%) and the mean patient age was 58.6 (sd 20.4) years. Overall, the
      prevalence of E. coli was 55.3% (1375 strains), with Enterococcus spp 10.2 %,
      Proteus mirabilis 4.8%, coagulase-negative staphylococci 4.3% and Klebsiella 3.8%
      being the next most frequently encountered species. High compliance with quality
      control program was observed. Susceptibility figures in E. coli were consistently
      low for many antimicrobial agents such as ampicillin (51.3%) and co-trimoxazole
      (74.6%) and higher for others such as gentamicin (87.9%) and ceftazidime (95.1%).
      Resistance rates were higher among male patients and increased according to the
      patient's age.

PMID- 17434823
TI  - In vitro activity of ceftibuten at sub-inhibitory concentrations in comparison
      with other antibiotics against respiratory and urinary tract pathogens.
AB  - Some new features of the in vitro activity of ceftibuten, an oral third
      generation cephalosporin, have been studied in reference to respiratory and
      urinary tract pathogens included in its antibacterial spectrum. At 0.25XMIC
      (minimum inhibitory concentration) and 0.5XMIC levels, ceftibuten was able to
      affect the biofilm production in 2/3 of both Escherichia coli and Proteus
      mirabilis strains, and reduced the number of strains capable of adhering to
      epithelial cells by about 35% in comparison to the control. Surface
      hydrophobicity was also influenced by ceftibuten and the other drugs at 0.25
      0.5XMIC. In general, no marked variation in the virulence traits of the pathogens
      studied were found by exposing bacteria to sub-MICs of ceftibuten. Plasmid loss
      (from 1.8 to 37.2%), and Flac transfer inhibition (about 30-50% reduction in the
      number of recombinants) were detected under the experimental conditions used.
      This study confirms the excellent antibacterial properties of ceftibuten by
      adding new information about the effects of this antibiotic against pathogens
      often involved in respiratory and urinary tract infections that may be treated
      with this compound, supporting the appropriate use of this cephalosporin.

PMID- 17434825
TI  - Analysis of fluoroquinolone resistance in clinical isolates of Mycobacterium
      tuberculosis from India.
AB  - Clinical isolates of Mycobacterium tuberculosis (47 ofloxacin-susceptible and 71
      ofloxacin-resistant) strains obtained from individual patients from various parts
      of India were analyzed for gyr A mutation in quinolone resistant determining
      region (QRDR). Most of the mutations were seen clustered in the codons 90, 94 and
      95, which is a hot spot region of QRDR. The types of mutations were correlated
      with the in vitro susceptibility pattern of the strains to ofloxacin. The
      mutations: A90V was found coded for low-level resistance (MIC <or=16 microg/ml),
      D94A and D94V were coded for moderate level resistance (MIC 32-64 microg/ml) and
      S91P, D94G and D94N were coded for high level resistance (MIC >64 microg/ml) to
      ofloxacin. The resistance to fluoroquinolones was observed predominantly due to
      gyr A mutations. There were 2 highly resistant strains that did not show any
      mutations for gyr A, were further analyzed for gyr B mutations and were found
      negative for any mutations. However, there were two novel mutations, namely R68G
      and L109V, which were found in sensitive strain that did not code for any change
      in the susceptibility pattern and require further investigation.

PMID- 17434826
TI  - Comparison of tablet and disk diffusion methods for fluconazole and voriconazole
      in vitro activity testing against clinical yeast isolates.
AB  - We have compared a commercially available tablet diffusion method for the in
      vitro antifungal susceptibility testing of fluconazole (FCZ) and voriconazole
      (VCZ) with the disk diffusion method M44 (CLSI) with 282 clinical yeast isolates.
      The superior stability of antifungal agents in tablets can explain the
      differences for each category of susceptibility by both methods.Neo-Sensitabs
      tablets antifungal susceptibility testing showed an excellent correlation (0.98
      for FCZ and 0.98 for VCZ at 24h and 0.96 for FCZ and 0.94 for VCZ at 48 h ), a
      reduced percentage of disagreements (4.6% and 8.2% for FCZ at 24h and 48 h
      respectively; 1.1% and 2.1% for VCZ at 24h and 48 h respectively) and the absence
      of statistically significant difference in comparison with the reference protocol
      for performing antifungal susceptibility testing with the agar diffusion method.

PMID- 17434827
TI  - Effect of a policy for restriction of selected classes of antibiotics on
      antimicrobial drug cost and resistance.
AB  - Based on the instructions of the National Organization of Pharmaceutical Agents
      (Greece) from July 1, 2003, quinolones, 3( rd )and 4(th )generation
      cephalosporins, carbapenems, monobactams, glycopeptides, oxazolidinones, and
      streptogramins were considered as "restricted" antibiotics that could be used
      only with the approval of an Infectious Disease specialist. We analyzed the
      effect of the policy on the consumption and cost of antibiotics as a group and of
      specific classes, adjusted for the patient load, as well as on the antimicrobial
      resistance of isolated bacteria. We analyzed 5 trimesters (2 prior and 3 after
      the implementation of the new policy). A 20% and 16% reduction in adjusted
      consumption [in daily defined doses (DDDs)] and cost, respectively, of the
      restricted antibiotics was accomplished during the first trimester after
      implementation of the new policy. However, this was accompanied by a 36% and 56%
      increase in adjusted consumption and cost, respectively, of unrestricted
      antibiotics. A logistic regression model that we performed showed that the new
      policy had an independent positive effect on the in vitro antimicrobial
      susceptibility of Pseudomonas aeruginosa (p=0.051) but not of Acinetobacter
      baumannii and Escherichia coli isolates. Our data suggest that there are
      considerable limitations to the programs aiming to reduce the consumption of
      restricted antibiotics through the approval of their use by specialists, at least
      in some settings.

PMID- 17434828
TI  - Survival of elderly bacteriuric subjects following long-term quinolone therapy.
AB  - This study aimed to determine whether long-term oral fluoroquinolone
      administration exerts a significant positive effect on mobility and mortality in
      elderly subjects with asymptomatic bacteriuria. 132 institutionalized patients
      were divided into 4 groups: groups A and B were treated with ofloxacin while
      groups C and D were positive and negative control groups. At 3 months following
      treatment discontinuation 57%, 53% and 26% of patients in groups A, B and C
      respectively had negative urine cultures and all subjects were alive. After 3
      years, positive cultures were 41.7%, 54.5% and 42.9% respectively for
      uncatheterized subjects per group vs. 13.3% for group D. In groups A, B, and C
      20%, 15% and 29% of survivors respectively had permanent bladder catheters vs.
      11.5% of survivors of group D. Survival in groups A, B and C, combined or per
      group did not differ significantly from group D, although it was shorter. "Pulse"
      antibiotic administration tended to perform better, in terms of clearing
      infection and maintaining continence. At 3 years, bacteriuria recurred and the
      need for bladder catheterization was doubled. Mortality increased independently
      of treatment. More elderly bacteriuric subjects should be studied to evaluate
      mobility and mortality issues.

PMID- 17434829
TI  - Antimicrobial prophylaxis in vaginal gynecologic surgery: a prospective
      randomized study comparing amoxicillin-clavulanic acid with cefazolin.
AB  - The aim of this prospective, randomized study was to compare amoxicillin
      clavulanic acid with cefazolin as ultra-short term prophylaxis in vaginal
      gynecologic surgery. It was conducted at the Department of Obstetrics and
      Gynecology, University of Bari. Patients were randomly allocated to receive
      amoxicillin-clavulanic acid (2.2 g) [Group A] or cefazolin (2 g) [Group B] as a
      single dose 30 minutes before surgery. Each patient was assessed daily until
      discharge to evidence febrile status and the presence of infections at the
      operative site, urinary tract and respiratory tract. In the amoxicillin
      clavulanic acid (Group A) and cefazolin (Group B) groups, overall 88 and 90
      patients, respectively, were evaluable for prophylactic efficacy at hospital
      discharge. Infectious complications were infrequent in both arms, with febrile
      morbidity occurring in 4 (4.5%) and 16 (8.9%) patients respectively in the
      amoxicillin-clavulanic acid and cefazolin groups (p=0.016). Urinary tract
      infections were higher but not significantly in the amoxicillin-clavulanic acid
      group (6.8% versus 4.4 %), whereas asymptomatic bacteriuria was detected in 2.2%
      of the patients in both groups. There was no respiratory tract infection or
      septic death in either group. It is concluded that ultra-short term prophylaxis
      with both amoxicillin-clavulanic acid and cefazolin is safe and effective in
      elective vaginal gynecologic surgery.

PMID- 17434830
TI  - Trends in risk factors and etiology of 606 cases of infective endocarditis over
      23 years (1984-2006) in slovakia.
AB  - The aim of this study was to assess trends in risk factors, etiology, outcome and
      treatment strategies for endocarditis over 23 years in Slovakia. A prospective
      survey of 606 cases of infective endocarditis (IE) was conducted from 1984-2006.
      Rheumatic fever as well as previous dental surgery showed decreasing trends
      within the last 23 years. Also embolic complications of IE declined along with
      increasing rates of surgically treated patients. No significant changes in
      etiology were detected apart from the fact that culture-negative endocarditis
      increased from 10.7% to 55.4% between 1998-2001. Surgically treated patients
      increased from 22.7% (1984-1990) to 50.1% (2002-2006) and mortality dramatically
      decreased from 26.7% (1984-1990) to 5.3% (2002-2006). Staphylococcus aureus and
      coagulase-negative staphylococci were the leading causes (22.4% - 48%) followed
      by viridans streptococci (12.2%-18.2%) were a relatively stable trend over 23
      years of IE in Slovakia.

PMID- 17434831
TI  - Efficacy of chemotherapeutic agents under hypoxic conditions in pulmonary
      adenocarcinoma multidrug resistant cell line.
AB  - Hypoxia is often observed in solid tumors. The aim of this study was to
      investigate the efficacy of seven cytotoxic drugs against the pulmonary
      adenocarcinoma multidrug-resistant cell line A549/MDR under hypoxia (3% O(2)),
      and to explore the possible mechanisms for the change of efficacy. The efficacy
      of cytotoxic drugs under hypoxic conditions was different from that under
      normoxia. Proliferation of A549/MDR cells was enhanced under hypoxia and no close
      correlation was found between proliferation and cytotoxic effects. Under hypoxia,
      the efficacy of rhodamine123 efflux was unchanged; the culture medium became more
      acidic and the generation of reactive oxygen species (ROS) was decreased. The
      intracellular fluorescence intensity of daunorubicin was much lower in this
      acidic microenvironment. These results indicate that susceptibility to drugs was
      greatly influenced by hypoxia and different intracellular drug concentrations
      induced by microenvironment acidification which may be the main cause of the
      change in drug efficacy. In addition, proliferation may change resistance to
      study drugs under hypoxia for A549/MDR cells. The decreased generation of ROS may
      be another reason for the resistance of A549/MDR cell line to daunorubicin under
      hypoxic conditions. Drug exclusion mediated by P-gp may not be the key reason.

PMID- 17434832
TI  - Clinical phase I and pharmacology study of gemcitabine (2', 2'
      difluorodeoxycytidine) administered in a two-weekly schedule.
AB  - Gemcitabine (dFdC) was tested in a Phase I trial at 14 doses (40-5700 mg/m(2)),
      administered every 2 weeks as a (1/2) -h infusion to 52 patients with refractory
      solid cancer. Gemcitabine and its deaminated metabolite difluorodeoxyuridine
      (dFdU), measured with HPLC, reached plasma peak levels of 2-3 microM at 40
      mg/m(2) which increased to 512 microM at 5700 mg/m(2). Gemcitabine was eliminated
      rapidly with a t(1/2) beta of 2.3-15.8 min in the 40-5700 mg/m(2) dose range,
      with one exception of 38 min at 4500 mg/m(2) . dFdU was still present at a
      plateau of +/- 20 microM from 4-24 h at doses >960 mg/m(2). Up to 3650 mg/m(2)
      linear pharmacokinetics were observed for gemcitabine, while those for dFdU were
      linear over the whole range. Gemcitabine clearance varied between 1.5-12.6 l/min
      and was 1.5-fold higher in males than in females (p= 0.024); its volume of
      distribution was 45.2-248 l. In lymphocytes peak levels of the active metabolite
      dFdCTP were 100-380 pmol/10( 6 )cells in the first course. Apparently a plateau
      was reached which was confirmed by incubation of white blood cells with
      increasing gemcitabine concentrations up to 500 microM, reaching a plateau of
      about 350 pmol/10(6 )cells; in contrast in cancer cells this concentration
      dependence did not exist and accumulation reached about 1590 pmol/10( 6 )cells.
      In tumors isolated from patients treated with gemcitabine dFdCTP reached about 70
      pmol/g wet weight. Gemcitabine itself was eliminated only to a limited extent in
      the urine, but dFdU was eliminated almost completely in the urine in the first 24
      h (51-92%). In conclusion, dFdC was rapidly eliminated in contrast to dFdU, which
      was present for at least 18 h, as well as dFdCTP in lymphocytes.

PMID- 17434833
TI  - Antimicrobial resistance among enterobacteriaceae causing uncomplicated urinary
      tract infections in Mauritius: consequences of past misuse of antibiotics.
AB  - A study was conducted to determine the nature and antimicrobial susceptibility of
      uropathogens in Mauritius in order to provide guidance on the empirical treatment
      of uncomplicated urinary tract infections. The study was based on urine samples
      sent for bacteriological investigation at the Central Health Laboratory from
      unhospitalized patients over a 3-month period. Information on organisms isolated
      in pure growth and their antibiotic susceptibility was collected and analyzed.
      Entero - bacteriaceae accounted for over 80% of the 260 isolates obtained during
      the study period, and showed high rates of resistance to ampicillin (80%), co
      trimoxazole (50%), nalidixic acid (34%) and ciprofloxacin (26%). Resistance to
      mecillinam and fosfomycin were only 2% and 0% respectively. The high rate of
      antimicrobial resistance in Enterobacteriaceae in urine is cause for concern.
      Fluoroquinolones may not be very reliable for empirical treatment of urinary
      tract infections in Mauritius. Alternatives such as pivmecillinam and fosfomycin
      should be considered.

PMID- 17434834
TI  - In vitro synergistic activity of colistin with aminoglycosides, beta-lactams and
      rifampin against multidrug-resistant gram-negative bacteria.

PMID- 17434835
TI  - E-test minimum inhibitory concentrations for tigecycline against nosocomial
      Acinetobacter baumannii strains.

PMID- 17434836
TI  - Once-daily tigecycline therapy of multidrug-resistant and non-multidrug-resistant
      gram-negative bacteremias.

PMID- 17434837
TI  - Correlation of the persistence or eradication of Porphyromonas gingivalis with
      pocket depth reduction in the treatment of periodontal disease.

PMID- 17434838
TI  - Conventional dose intensive immunochemotherapy regimen in an adult patient with
      very late relapse of Burkitt's lymphoma.

PMID- 17434843
TI  - Prevalence of antiretroviral drug resistance and resistance-associated mutations
      in antiretroviral therapy-naive HIV-infected individuals from 40 United States
      cities.
AB  - BACKGROUND: Transmission of drug-resistant HIV strains to antiretroviral therapy
      (ART)-naive subjects can negatively impact therapy response. As treatment
      strategies and utilization of antiretroviral drugs evolve, patterns of
      transmitted mutations may shift. METHOD: Paired genotypic and phenotypic
      susceptibility data were retrospectively analyzed for 317 ART-naive, HIV-infected
      subjects from 40 small and major metropolitan cities in the Northeastern,
      Midwestern, Southern, Southwestern, and Northwestern United States during 2003.
      RESULTS: Using current (January 2007) PhenoSense cutoffs, HIV-from 8% of subjects
      had reduced susceptibility to > or = 1 drug. By class, < 1% had reduced
      susceptibility to protease inhibitors (PIs), and 1% had reduced susceptibility to
      nucleoside reverse transcriptase inhibitors (NRTIs); reduced susceptibility to >
      or = 1 non-nucleoside reverse transcriptase inhibitor (NNRTIs) was seen in 7% of
      subjects, with 4% of all subjects having reduced susceptibility to all NNRTIs.
      IAS-USA-defined NRTI, NNRTI, and/or major PI HIV-drug resistance-associated
      mutations were detected for 0% of the subjects. HIV risk factors included
      homosexual contact (74%), heterosexual contact (28%), and injectable drug
      use/transfusion/other (7%). Reduced susceptibility to > or = 1 drug was
      significantly higher (p = .034) for white subjects than African Americans and
      Hispanics/others. CONCLUSION: The high prevalence of drug resistance in these ART
      naive subjects suggests that transmitted resistance is occurring widely within
      the United States. HIV genotyping and/or phenotyping for antiretroviral-naive
      patients seeking treatment should be considered, especially if the therapy will
      include an NNRTI.

PMID- 17434844
TI  - Resistance costs and future drug options of antiretroviral therapies: analysis of
      the role of NRTIs, NNRTIs, and PIs in a large clinical cohort.
AB  - OBJECTIVE: To investigate future drug options (FDOs), resistance cost (RCVF), and
      virologic response to genotypic-driven rescue highly active antiretroviral
      therapy (HAART), according to type of therapy. METHOD: This was a retrospective
      analysis in naive or antiretroviral-experienced patients. Virologic response was
      defined as HIV RNA <50 copies. RESULTS: There were 108 patients failing first
      line HAART; there were 328 experienced patients. FDOs were reduced in subjects
      failing a thymidine-analogue (TA) regimen (median 3.65, IQR 1.29 ) compared to
      patients without TA (median 3.82, IQR 1.12) (p = .011). FDOs after first failure
      were higher for patients with non-nucleoside reverse transcriptase inhibitor
      (NNRTI; median 3.82; IQR 1.24) than with protease inhibitor (PI; median 3.64, IQR
      1.15) (p = .027). In experienced patients, FDOs were much higher for TA (p =
      .005). Patients responding to genotypic-modified regimens had higher FDOs (median
      3.9 4, IQR 2.53) than patients not responding (median 2.18, IQR 3.65) (p >
      .0001). Switching from an NNRTI-based HAART to a boosted PI had a higher chance
      (48.1%) of achieving a full virologic suppression, compared to switching from PI
      to NNRTI (21.4%, p < .0001). CONCLUSION: FDOs and RCVF are parameters that can
      quantify the therapeutic choices at virologic failure. Different drugs induce
      different FDOs and RCVF. In successive-line regimens, the higher antiviral effect
      and genetic barrier of boosted PIs may overcome the limits of using nucleoside
      reverse transcriptase backbones, with only partial effectiveness.

PMID- 17434845
TI  - Pilot study of a novel short-cycle antiretroviral treatment interruption
      strategy: 48-week results of the five-days-on, two-days-off (FOTO) study.
AB  - PURPOSE: The challenges associated with daily lifelong antiretroviral therapy
      (ART) have stimulated interest in alternative treatment schedules, including
      planned, cyclical interruptions of therapy in patients with virologic suppression
      and sufficient CD4+ T-cell counts. METHOD: We conducted a 48-week, open-label,
      single-arm, prospective pilot study of a novel short-cycle treatment interruption
      strategy. Upon enrollment, 30 HIV+ individuals with a history of durable viral
      suppression on daily ART changed their weekly treatment schedule to 5 consecutive
      days on treatment (typically Monday through Friday) followed by 2 days off
      treatment (five-on, two-off, or FOTO treatment schedule). RESULTS: At 24 and 48
      weeks, as-treated analysis revealed that virologic suppression was maintained in
      26/29 subjects (89.6%), including 100% of subjects taking efavirenz-based
      regimens. Participants adhered well to the FOTO treatment schedule and expressed
      a strong preference for the FOTO treatment schedule compared to daily ART.
      CONCLUSION: If validated, the FOTO treatment strategy with efavirenz-based
      regimens could avoid the viremia witnessed in longer cycle structured treatment
      interruptions yet still ameliorate a number of problems associated with the
      current paradigm of daily ART for HIV infection, including the high cost of
      therapy and the pill fatigue that, in many patients, leads to erratic adherence
      and ultimately treatment failure.

PMID- 17434846
TI  - Quality of life and tolerability after administration of enfuvirtide with a thin
      walled needle: QUALITE Study.
AB  - PURPOSE: Use of enfuvirtide-containing regimens leads to virologic and
      immunologic benefits and quality of life (QoL) improvements. This study (QUALITE)
      was designed to primarily identify baseline predictors of QoL improvements and
      characterize injection site reaction (ISR) signs/symptoms using a thinner/shorter
      needle. METHOD: Enfuvirtide-naive, antiretroviral (ARV)-experienced patients with
      CD4 counts >50 cells/mm3 enrolled in this prospective, 12-week, multisite, open
      label study. Patients self-administered enfuvirtide, 90 mg bid, using thin
      walled, 31-gauge/8-mm needles in combination with other ARVs. QoL was evaluated
      with MOS-HIV. RESULTS: Of the 361 patients enrolled, 346 contributed to QoL
      assessments. Baseline median HIV RNA and CD4 counts were 4.21 log10 copies/mL and
      203 cells/mm3, respectively. Although no baseline factors were predictive of week
      12 QoL improvement, 9 of 11 MOS-HIV domain scores improved significantly,
      including physical function (p = .0002) and mental health (p = .0006). Through
      week 12, 87% of patients reported ISRs; 59% and 28% reported worst
      pain/discomfort grade < or = 1 and grade > or = 2, respectively, and none were
      considered serious. Patients reported that self-injection minimally impacted
      daily functioning or activities. CONCLUSION: Although no predictors of QoL were
      identified, significant improvements in QoL were observed with minimal clinically
      significant ISRs (grade > or = 2) using the 31-gauge/8-mm needle.

PMID- 17434847
TI  - Virologic and immunologic impact and durability of enfuvirtide-based
      antiretroviral therapy in HIV-infected treatment-experienced patients in a
      clinical setting.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of enfuvirtide-based therapy
      in treatment-experienced patients in a clinical setting. METHOD: Retrospective
      study of treatment-experienced patients receiving enfuvirtide-based therapy for a
      minimum of 2 months. Endpoints included virologic suppression, virologic rebound,
      immunologic response, and adverse events. RESULTS: Sixty-four patients were
      eligible for inclusion in the analysis. Median baseline viral load and CD4+ count
      were 4.7 log10 copies/mL (interquartile range [IQR], 4.0-5.2) and 150 cells/mm3
      (IQR, 60-250), respectively. At month 12, viral load declined by a median of 2.53
      log10 copies/mL (IQR, 0.97-3.12). The unadjusted median time to virologic
      suppression was 7.7 months (95% CI 4.1-10.4 months). Baseline viral load and
      number of protease inhibitors in the current regimen were significantly
      associated with virologic suppression following multivariate analysis (hazard
      ratio [HR] 0.45, 95% CI 0.31-0.63, p < .0001, and HR 0.51, 95% CI 0.27-0.94, p =
      .03, respectively). Among the 42 patients who attained sustained virologic
      suppression, 10 experienced virologic rebound during a median follow-up of 13.3
      months (IQR, 7.0-19.1). Injection site reactions were reported in 33 (52%)
      patients, resulting in treatment discontinuation in nine patients. CONCLUSION:
      Enfuvirtide-based therapy provides durable antiretroviral activity for treatment
      experienced patients in a clinical setting.

PMID- 17434848
TI  - Comparison of direct and indirect measurement of LDL-C in HIV-infected
      individuals: ACTG 5087.
AB  - BACKGROUND: Hypertriglyceridemia is common in HIV-infected individuals on
      antiretroviral therapy. Triglyceride (TG) levels >400 mg/dL interfere with the
      accurate determination of low-density lipoproteins (LDL-C) by the Friedewald
      equation, making it difficult to assess coronary heart disease risk. OBJECTIVE:
      The objective of this study is to compare the agreement of the direct LDL-C assay
      and the Friedewald equation with a reference ultracentrifugation method in the
      estimation of LDL-C concentrations. METHOD: Samples from ACTG 5087 were assayed
      by ultracentrifugation and a direct enzymatic assay and calculated using the
      Friedewald equation. RESULTS: In subjects with TG <400 mg/dL (n = 271), 90% of
      the direct LDL-C values and Friedewald calculations were within 30 mg/dL and 32
      mg/dL of the ultracentrifugation values, respectively. With TG > or = 400 mg/dL
      (n = 186), 90% of the direct assay and Friedewald observations were within 68
      mg/dL and 120 mg/dL of the ultracentrifugation results, respectively. Only 27% of
      the LDL-C values were within 15 mg/dL of the ultracentrifugation LDL-C results
      for direct assay and 16.3% for the Friedewald equation. CONCLUSION: The direct
      LDL-C assay and the calculated LDL-C values did not display adequate agreement
      with the reference ultracentrifugation method. In subjects with TG >400 mg/dL,
      the direct assay overestimates the actual LDL-C whereas the Friedewald
      calculation underestimates the actual LDL. Clinical usage of these methods may
      lead to misclassification of the severity of dyslipidemia, resulting in improper
      management.

PMID- 17434849
TI  - Pravastatin in HIV-infected patients treated with protease inhibitors: a placebo
      controlled randomized study.
AB  - PURPOSE: The objectives of the study were to assess the effects of pravastatin on
      plasma HIV RNA, lipid parameters, and protease inhibitor (PI) concentrations in
      patients treated with PI-containing regimens and with total cholesterol (TC) > or
      = 5.5 mmol/L. METHOD: A clinical trial including patients randomized to receive
      pravastatin or matching placebo for 12 weeks was implemented. RESULTS: Twelve
      patients were included in the pravastatin group and 9 in the placebo group. At
      week 12 (W12), no patient had experienced virological failure. Between week 0
      (W0) and W12, the median differences for TC were -1.4 mmol/L in the pravastatin
      group and +0.2 mmol/L in the placebo group (p = .005); for LDL, they were -1.0
      mmol/L and +0.3 (p = .007), respectively. A significant decrease of the PI
      concentration (12 hours after administration) ratio W12 - W0/W0 was noticed in
      the pravastatin group (-0.2 [interquartile range, -0.3 to -0.1] as compared with
      the placebo group (0.1 [IQR, 0.0 to 0.3]) (p = .03). When the study was
      restricted to patients treated with lopinavir/ritonavir, a decrease from 3.8
      microg/mL at baseline to 2.9 mug/mL at W12 was noticed in the pravastatin arm (p
      = .04) but not in the control arm (p = 1.00). No clinical adverse event reached a
      severity of grade 3. CONCLUSION: We observed in this study that the use of
      pravastatin in PI-treated patients was not associated with major change in the
      plasma HIV RNA on 12 weeks of follow-up. However, we found a trend of decrease of
      the trough PI concentration at W12, suggesting a possible drug-drug interaction
      of pravastatin on PI metabolism.

PMID- 17434852
TI  - Agent-based modelling as scientific method: a case study analysing primate social
      behaviour.
AB  - A scientific methodology in general should provide two things: first, a means of
      explanation and, second, a mechanism for improving that explanation. Agent-based
      modelling (ABM) is a method that facilitates exploring the collective effects of
      individual action selection. The explanatory force of the model is the extent to
      which an observed meta-level phenomenon can be accounted for by the behaviour of
      its micro-level actors. This article demonstrates that this methodology can be
      applied to the biological sciences; agent-based models, like any other scientific
      hypotheses, can be tested, critiqued, generalized or specified. We review the
      state of the art for ABM as a methodology for biology and then present a case
      study based on the most widely published agent-based model in the biological
      sciences: Hemelrijk's DomWorld, a model of primate social behaviour. Our analysis
      shows some significant discrepancies between this model and the behaviour of the
      macaques, the genus used for our analysis. We also demonstrate that the model is
      not fragile: its other results are still valid and can be extended to compensate
      for these problems. This robustness is a standard advantage of experiment-based
      artificial intelligence modelling techniques over analytic modelling.

PMID- 17434853
TI  - Stiff reminders, and regenerating for the future: a commentary on "Man as the
      measure of all things".
AB  - Margrit Hugentobler's article, "Man as the Measure of All Things: A Limiting
      Approach to Urban Regeneration?," took to task the challenges of sustainable
      development that neither governments nor industry have yet met on the scale that
      is needed. From a planner's perspective, she gives a philosophical context. In
      essence, her message is that through thoughtful regeneration, urban environments
      can become more sustainable and that urban regeneration can meet a variety of
      human and environmental needs. She proposes a new model, using a
      multidisciplinary approach to urban regeneration and development.

PMID- 17434854
TI  - Evidence of political interference / EPA air pollution decision threatens public
      health: science disregarded, misrepresented on particulate matter standard.
AB  - Political interference with federal agency science threatens our health, safety,
      and environment. The Environmental Protection Agency's recent air pollution rules
      on fine particulate matter (PM) are particularly egregious assaults on public
      health and the integrity of science in federal policy making. The Union of
      Concerned Scientists (UCS) has been actively monitoring and documenting cases of
      such interference and mobilizing scientists and citizens alike to push for
      reforms. Information on the PM case, and many others, are available on the UCS
      website (http://www.ucsusa.org).

PMID- 17434855
TI  - Silenced science: air pollution decision-making at the EPA threatens public
      health.
AB  - The saga of the Environmental Protection Agency's new particulate matter (PM)
      rule is yet another example of this Administration's disregard for and disrespect
      of science and scientists--and may signal the beginning of a disturbing trend to
      reduce the role of science in protecting the quality of our air. Political
      interference in the PM case is clear. And more trouble may be in the wings when
      it comes to acceptable levels of ozone pollution and the process for setting the
      National Ambient Air Quality Standards (NAAQS). For several years, the Union of
      Concerned Scientists has been actively monitoring and documenting the misuse of
      science in public policy-making. Consider this a call to arms. Now is the time to
      engage your elected officials on these issues.

PMID- 17434856
TI  - Are we failing vulnerable workers? The case of black women in poultry processing
      in rural North Carolina.
AB  - In 1989, North Carolina Occupational Safety and Health Administration (OSHA)
      inspectors cited two poultry processing plants in northeastern North Carolina for
      serious repetitive motion problems. In 1990, investigators from the National
      Institute for Occupational Safety and Health confirmed significant upper
      extremity musculoskeletal symptoms and disorders among workers. We now report on
      analyses of baseline data collected from a cohort of women employed in one of
      these plants. The plant, which is the largest employer of women in the area, is
      located in a sparsely populated area with a black majority where nearly one-third
      of the population lives below the poverty level. Conditions we report suggest
      failure of existing health and safety systems, both regulatory and consultative,
      to prevent morbidity among vulnerable women in this industry, as well as social
      and economic conditions that influence availability of work and use of benefits
      to which they are entitled.

PMID- 17434857
TI  - San Sebastian: the social and political effects of sugar mill closure in Mexico.
AB  - Mexico's sugar mills face an uncertain future: the closure of San Sebastian may
      well presage others if the climate for sugar production on national and
      international levels does not improve. While the continued squeezing of small
      cane producers reflects processes affecting peasant agriculture generally in
      Mexico, and indeed beyond, the fate of the mill workers made redundant when the
      mill closed similarly mirrors broad tendencies in labor in both the developed and
      developing world under neoliberalism. Former workers fell back upon personal,
      family, and community resources by migrating to the U.S. or locally
      reconstructing livelihoods characterized by a reduction in income, security, and
      access to social benefits. This article reports on the impact of the mill closure
      on the livelihoods of former mill worker families in the community of San
      Sebastian and offers some observations on their responses to the situation.

PMID- 17434858
TI  - Understanding women's work: steps toward transformation--an introduction.
AB  - A session at the 2005 Delhi Congress on Women, Work and Health was entitled
      "Social movements and research on women, work and health: How can researchers and
      community members work together on current problems?" and described researcher
      worker collaboration to gain recognition for the constraints and requirements of
      women's jobs. Suffering in the workplace may appear to come primarily from such
      visible aggressors as toxins and heavy weights, but its ultimate cause is the
      powerlessness, isolation, and denigration that sap workers' ability to fight
      back. Participatory research projects described here have promoted solidarity and
      encouraged the transformation of working conditions.

PMID- 17434859
TI  - Precarious existence and deteriorating work conditions for women in India:
      implications for health.
AB  - The Indian economy has experienced economic growth post-1991 but has demonstrated
      an inability to generate adequate employment and even less of "quality"
      employment for much of its labor force. This article is based on data collected
      from conversations with women workers on the theme of "women, work and health,"
      with an emphasis on, one, task allotment and working conditions in the household;
      and two, those related to conditions of work at the worksite and the gendered
      experience of such work. While narratives cannot establish causality between
      particular work environments and related adverse outcomes, they nevertheless
      provide crucial insights into what is likely to be blighting these women's lives.
      Advocates of women's work outside their home need to pay attention to both their
      remuneration for work and the costs to their health and well-being of such
      employment, so that policies aimed at employment generation also are sensitive to
      the adverse outcomes of such employment.

PMID- 17434860
TI  - Paradoxical payoffs: migrant women, informal sector work, and HIV/AIDS in South
      Africa.
AB  - In post-apartheid South Africa, there has been a significant rise in women's out
      migration from rural areas and across its territorial borders for economic
      purposes resulting in gender reconfiguration of migration streams. Alongside,
      there has been a simultaneous increase in the participation of women in the labor
      force. However, this has mostly grown in the informal sector,1 which is often
      associated with low earnings and insecure working conditions. One consequence has
      been the increasing reliance of migrant women on survivalist activities such as
      informal sexual exchanges that increase their risk of contracting HIV infection.
      Insecure working environments also expose migrant women to sexual abuses. This
      article is based on the author's work in South Africa's major urban centers and
      examines the nature of the relationship between the increased migration of black
      African women in South Africa, the nature of their work, and their resultant
      vulnerability to HIV/AIDS.

PMID- 17434861
TI  - Restructuring of the Quebec health network and its effects on the profession of
      home health aides and their occupational health and safety.
AB  - The Quebec health sector is facing profound macroeconomic and macro
      organizational changes. This article addresses the impact of these changes on the
      work of home health aides (HHAs) and their occupational health and safety (OHS).
      The study was carried out in the home care services of four local community
      service centers (CLSCs) with different organizational characteristics. It is
      based on an analysis by triangulation of 66 individual and group interviews, 11
      work days, and 35 multidisciplinary or professional meetings observed, as well as
      administrative documents. HHAs are experiencing an erosion of their job because
      the relational and emotional components of their work are disappearing. This
      results in an increase in musculoskeletal and psychological health problems. This
      study also shows that managers' decisions can reduce or increase the HHAs' work
      constraints. Stability in the clientele served and the possibility of organizing
      their routes are good examples of positive impacts.

PMID- 17434862
TI  - Is work in education child's play? Understanding risks to educators arising from
      work organization and design of work spaces.
AB  - The educational sector exposes its primarily female work force to numerous
      psychosocial risk factors. At the request of the education workers', ergonomists
      developed a participatory research project in order to understand the
      determinants of the difficulties experienced by special education technicians.
      These technicians work with students presenting behavioral and learning
      difficulties as well as developmental and mental health problems. Eighteen
      technicians were interviewed and the work of seven technicians and two teachers
      was observed. Technicians prevent and manage crisis situations and help students
      acquire social skills. Coordination with teachers is made difficult by the fact
      that most technicians work part time, part year, and many technicians' work areas
      and classrooms are physically distant one from another. Most technicians change
      schools each year and must continually reconstruct work teams. Management
      strategies and poorly adapted working spaces can have important repercussions on
      coordination among educators and on technicians' capacity to help students and
      prevent aggressive behavior.

PMID- 17434863
TI  - Questions related to a research intervention carried out with female and male
      public school workers.
AB  - This article presents a health intervention-research project done with workers in
      Brazilian public schools. Health, as we understand it, is linked both to the way
      in which we live and to our capacity to change that way of life. We emphasize the
      critical importance of initiating dialogue between research professionals and
      workers (co-investigators) in order to understand and transform work situations.
      We highlight the effects of debates about gender relations that led to work
      transformations. Such debates made it easier for workers and researchers to
      understand that men and women experience job requirements differently. We found
      that some staff favored reproduction of a sexually differentiated school system.
      These debates also allowed male and female workers to make their family members
      aware of difficulties in their work, unknown to society in general. We considered
      how to expand this research process, including examples of how the work was
      transformed.

PMID- 17434864
TI  - The Boston-area HASWIC Research Circle: an innovative participatory method for
      coloring in the picture of a special work environment.
AB  - Recent qualitative studies have investigated some of the hazards affecting women
      in non-traditional trades such as construction. However, one-time interactions
      among researcher participants, and between researchers and participants, in
      standard settings such as focus groups and interviews, cannot provide the time,
      space, and relationships to fully explore tradeswomen's in-depth knowledge of
      their work environment. This study applied a Scandinavian method called the
      Research Circle to convene a group of experienced women construction workers
      repeatedly over a period of two years so they could collaborate with researchers
      in explaining workplace issues. The results both validated and expanded upon
      previous findings about health and safety for women in construction, including
      gender discrimination, lack of access to sanitary facilities, retaliation for
      reporting hazards and injuries, and inadequate training and equipment. Especially
      important, findings illustrate some of the complex hierarchical social structures
      involved in both female and male construction workers responding to hazardous
      conditions.

PMID- 17434865
TI  - Psychosocial risk factors among telephone service workers: a study of the
      interaction between customer and worker.
AB  - Many activities in the telephone industry involve interaction with customers,
      including both traditional (for example, client assistance) and emerging services
      (product sales). Interaction with customers has been reported to cause stress in
      workers. The study was initiated as a consequence of changes in dialing of long
      distance numbers. The main sources of stress among workers in Traffic and
      Customer Services Departments were analyzed, together with the resulting
      psychological distress and other health symptoms. Information was gathered
      through semi-structured interviews and a questionnaire containing the Spanish
      version of the Job Content Questionnaire, as well as psychological strain and
      health symptoms items. Questions developed specifically for this study concerned
      emotional demands, client interactions, and mechanisms used to deal with violent
      or unpleasant interactions. Workers received valuable information from the study
      that empowered them to demand improved working conditions.

PMID- 17434866
TI  - The final statement of the National Seminar on Environment and Worker Health,
      Bogota, February 23-25, 2006.

PMID- 17434870
TI  - Social franchising of TB care through private GPs in Myanmar: an assessment of
      treatment results, access, equity and financial protection.
AB  - This article assesses whether social franchising of tuberculosis (TB) services in
      Myanmar has succeeded in providing quality treatment while ensuring equity in
      access and financial protection for poor patients. Newly diagnosed TB patients
      receiving treatment from private general practitioners (GPs) belonging to the
      franchise were identified. They were interviewed about social conditions, health
      seeking and health care costs at the time of starting treatment and again after 6
      months follow-up. Routine data were used to ascertain clinical outcomes as well
      as to monitor trends in case notification. The franchisees contributed 2097 (21%)
      of the total 9951 total new sputum smear-positive pulmonary cases notified to the
      national TB programme in the study townships. The treatment success rate for new
      smear-positive cases was 84%, close to the World Health Organization target of
      85% and similar to the treatment success of 81% in the national TB programme in
      Myanmar. People from the lower socio-economic groups represented 68% of the TB
      patients who access care in the franchise. Financial burden related to direct and
      indirect health care costs for tuberculosis was high, especially among the poor.
      Patients belonging to lower socio-economic groups incurred on average costs
      equivalent to 68% of annual per capita household income, with a median of 28%.
      However, 83% of all costs were incurred before starting treatment in the
      franchise, while 'shopping' for care. During treatment in the franchise, the cost
      of care was relatively low, corresponding to a median proportion of annual per
      capita income of 3% for people from lower socio-economic groups. This study shows
      that highly subsidized TB care delivered through a social franchise scheme in the
      private sector in Myanmar helped reach the poor with quality services, while
      partly protecting them from high health care expenditure. Extended outreach to
      others parts of the private sector may reduce diagnostic delay and patient costs
      further.

PMID- 17434869
TI  - A common variant in the FTO gene is associated with body mass index and
      predisposes to childhood and adult obesity.
AB  - Obesity is a serious international health problem that increases the risk of
      several common diseases. The genetic factors predisposing to obesity are poorly
      understood. A genome-wide search for type 2 diabetes-susceptibility genes
      identified a common variant in the FTO (fat mass and obesity associated) gene
      that predisposes to diabetes through an effect on body mass index (BMI). An
      additive association of the variant with BMI was replicated in 13 cohorts with
      38,759 participants. The 16% of adults who are homozygous for the risk allele
      weighed about 3 kilograms more and had 1.67-fold increased odds of obesity when
      compared with those not inheriting a risk allele. This association was observed
      from age 7 years upward and reflects a specific increase in fat mass.

PMID- 17434871
TI  - Enhancing the latent nucleotide triphosphate flexibility of the glucose-1
      phosphate thymidylyltransferase RmlA.
AB  - Nucleotidyltransferases are central to nearly all glycosylation-dependent
      processes and have been used extensively for the chemoenzymatic synthesis of
      sugar nucleotides. The determination of the NTP specificity of the model
      thymidylyltransferase RmlA revealed RmlA to utilize all eight naturally occurring
      NTPs with varying levels of catalytic efficiency, even in the presence of
      nonnative sugar-1-phosphates. Guided by structural models, active site
      engineering of RmlA led to alterations of the inherent pyrimidine/purine bias by
      up to three orders of magnitude. This study sets the stage for engineering single
      universal nucleotidyltransferases and also provides new catalysts for the
      synthesis of novel nucleotide diphosphosugars.

PMID- 17434872
TI  - Molecular determinants for the selective inhibition of cyclooxygenase-2 by
      lumiracoxib.
AB  - Lumiracoxib is the first example of a marketed COX-2 inhibitor of the arylacetic
      acid class, and it is reported to be the most selective COXIB in vivo. However,
      the molecular basis of its COX-2 inhibition has not been completely defined.
      Using standard assays, lumiracoxib was found to be a poor inhibitor of purified
      ovine COX-1 and a relatively weak inhibitor of purified human COX-2. The extent
      of COX-2 inhibition plateaued at around 50% and suggested that the inhibitor may
      be reversibly bound to the enzyme. Kinetic studies with lumiracoxib demonstrated
      that it was a time-dependent and slowly reversible inhibitor of human COX-2 that
      exhibited at least two binding steps during inhibition. Derivatives of
      lumiracoxib were synthesized with or without the methyl group on the phenylacetic
      acid ring and with various substitutions on the lower aniline ring. Inhibition
      studies demonstrated that the methyl group on the phenylacetic acid ring is
      required for COX-2 selectivity. The chemical identity and position of the
      substituents on the lower aniline ring were important in determining the potency
      and extent of COX inhibition as well as COX-2 selectivity. Mutation of Ser-530 to
      Ala or Val-349 to Ala or Leu abolished the potent inhibition observed with wild
      type human COX-2 and key lumiracoxib analogs. Interestingly, a Val-349 to Ile
      mutant was inhibited with equal potency to human COX-2 with 2,6-dichloro-, 2,6
      dimethyl-, or 2-chloro-6-methyl-substituted inhibitors and, in the case of
      lumiracoxib, actually showed an increase in potency. Taken together with a recent
      crystal structure of a lumiracoxib-COX-2 complex, the kinetic analyses presented
      herein of the inhibition of mutant COX-2s by lumiracoxib allows the definition of
      the molecular basis of COX-2 inhibition.

PMID- 17434873
TI  - Effects of single nucleotide polymorphisms on Toll-like receptor 3 activity and
      expression in cultured cells.
AB  - Recognition of double-stranded RNA by Toll-like receptor 3 (TLR3) will increase
      the production of cytokines and chemokines through transcriptional activation by
      the NF-kappaB protein. Over 136 single-nucleotide polymorphisms (SNPs) in TLR3
      have been identified in the human population. Of these, four alter the sequence
      of the TLR3 protein. Molecular modeling suggests that two of the SNPs, N284I and
      L412F, could affect the packing of the leucine-rich repeating units in TLR3.
      Notably, L412F is reported to be present in 20% of the population and is higher
      in the asthmatic population. To examine whether the four SNPs affect TLR3
      function, each were cloned and tested for their ability to activate the
      expression of TLR3-dependent reporter constructs. SNP N284I was nearly completely
      defective for activating reporter activity, and L412F was reduced in activity.
      These two SNPs did not obviously affect the level of TLR3 expression or their
      intracellular location in vesicles. However, N284I and L412F were
      underrepresented on the cell surface, as determined by flow cytometry analysis,
      and were not efficiently secreted into the culture medium when expressed as the
      soluble ectodomain. They were also reduced in their ability to act in a dominant
      negative fashion on the wild type TLR3 allele. These observations suggest that
      N284I and L412F affect the activities of TLR3 needed for proper signaling.

PMID- 17434874
TI  - A specific adaptation in the a subunit of thermoalkaliphilic F1FO-ATP synthase
      enables ATP synthesis at high pH but not at neutral pH values.
AB  - Analysis of the atp operon from the thermoalkaliphilic Bacillus sp. TA2.A1 and
      comparison with other atp operons from alkaliphilic bacteria reveals the presence
      of a conserved lysine residue at position 180 (Bacillus sp. TA2.A1 numbering)
      within the a subunit of these F(1)F(o)-ATP synthases. We hypothesize that the
      basic nature of this residue is ideally suited to capture protons from the bulk
      phase at high pH. To test this hypothesis, a heterologous expression system for
      the ATP synthase from Bacillus sp. TA2.A1 (TA2F(1)F(o)) was developed in
      Escherichia coli DK8 (Deltaatp). Amino acid substitutions were made in the a
      subunit of TA2F(1)F(o) at position 180. Lysine (aK180) was substituted for the
      basic residues histidine (aK180H) or arginine (aK180R), and the uncharged residue
      glycine (aK180G). ATP synthesis experiments were performed in ADP plus P(i)
      loaded right-side-out membrane vesicles energized by ascorbate-phenazine
      methosulfate. When these enzyme complexes were examined for their ability to
      perform ATP synthesis over the pH range from 7.0 to 10.0, TA2F(1)F(o) and aK180R
      showed a similar pH profile having optimum ATP synthesis rates at pH 9.0-9.5 with
      no measurable ATP synthesis at pH 7.5. Conversely, aK180H and aK180G showed
      maximal ATP synthesis at pH values 8.0 and 7.5, respectively. ATP synthesis under
      these conditions for all enzyme forms was sensitive to DCCD. These data strongly
      imply that amino acid residue Lys(180) is a specific adaptation within the a
      subunit of TA2F(1)F(o) to facilitate proton capture at high pH. At pH values near
      the pK(a) of Lys(180), the trapped protons readily dissociate to reach the
      subunit c binding sites, but this dissociation is impeded at neutral pH values
      causing either a blocking of the proposed H(+) channel and/or mechanism of proton
      translocation, and hence ATP synthesis is inhibited.

PMID- 17434875
TI  - All causes of mortality in male professional soccer players.
AB  - BACKGROUND: Despite the great public concern for the health status of
      professional soccer players, no formal study on mortality from all causes in
      soccer players has been performed so far. A study on mortality rates of
      professional soccer players in Italy between 1975 and 2003 was conducted.
      METHODS: A total of 5389 players, age 14-35 years at enrollment were identified
      from public sources, and actively followed up for vital status from birth up to
      31 December 2003, for 204 125 subject-years of follow-up. Overall and cause
      specific mortality rates were calculated; expected number of deaths was
      calculated by applying the calendar period and age cause-specific mortality rates
      for men to the cohort of soccer players. The ratios between the observed and
      expected deaths gave the Standardized Mortality Ratios. RESULTS: Deaths from
      diseases of the circulatory system, cancer and immune deficiency were
      significantly lower than expected. The SMR for car accidents was 2.23 (95% CI
      1.46-3.27). There were four deaths for Amyotrophic Lateral Sclerosis (ALS), and
      0.2 expected, giving a SMR of 18.18 (95% CI 5.00-46.55). CONCLUSION: The pubic
      health impact of these findings has to be balanced against the significant
      observed lower mortality for cancer and cardiovascular disease. However, the
      early age at death, and the youthful composition of the cohort pose questions on
      the relative weight of ALS mortality in this population in the coming years.

PMID- 17434876
TI  - Physical activity patterns of kindergarten children in comparison to teenagers
      and young adults.
AB  - BACKGROUND: Due to the increasing occurrence of obesity and low physical activity
      (PA) reported in school children there is a need to investigate PA patterns of
      preschool children. Our aim was to identify the PA of preschool children in
      comparison to the PA of teenagers and young adults. METHODS: PA of 104 Czech
      preschool children (aged 5-7 years), 1174 teenagers (aged 12-17 years) and 787
      young adults (aged 18-24 years) was determined using Caltrac accelerometery. PA
      was evaluated on the basis of activity energy expenditure (AEE--kcal kg(-1) day(
      1)). Subjects were monitored over 7 days to include a weekend. RESULTS: The AEE
      in preschool children was significantly higher in comparison to all age groups of
      teenagers and young adults during both weekdays and at the weekend (P<0.0001). On
      weekdays during leisure time, preschoolers were considerably more physically
      active than all categories of teenagers and young adults (P<0.001). Preschoolers
      show similarities in PA level between weekdays and weekends, unlike the older age
      groups. CONCLUSION: It seems to appear that organized daily PA (2x20 min of
      exercising on carpet, 50-70 min of walking outdoors) in preschool children along
      with enough space for spontaneous PA establishes prerequisites for their further
      healthy development.

PMID- 17434878
TI  - Plasmid-mediated quinolone resistance determinant qnrS1 found in Salmonella
      enterica strains isolated in the UK.
AB  - OBJECTIVES: To determine the prevalence of qnr genes in selected Salmonella
      enterica and Escherichia coli isolated in the UK. METHODS: One hundred and
      eighteen S. enterica and 103 E. coli were screened for qnrA, qnrB and qnrS by
      PCR. Transferability of qnr plasmids was assessed and isolated plasmids compared
      with previously identified qnr plasmids by restriction fragment length
      polymorphism analysis and hybridization experiments. PCRs and sequencing
      identified co-transferred beta-lactamase genes and mutations in the quinolone
      resistance-determining region of gyrA. RESULTS: Only six S. enterica strains
      belonging to four serotypes (Stanley, Typhimurium, Virchow and Virginia) were
      positive for qnrS1. qnrS1 was present on plasmids of 13.5 kb (TPqnrS-1a and -1b)
      in Typhimurium and Virginia isolates, 44 kb (TPqnrS-2) in two Virchow isolates
      and >148 kb (TPqnrS-3a and -3b) in two Stanley isolates. bla(TEM-1) and a group 9
      bla(CTX-M) were co-transferred on TPqnrS-2 and TPqnrS-3b. Hybridization of a
      qnrS1 probe to digested qnrS1 plasmids suggested qnrS1 on TPqnrS-2 may be located
      in a similar genetic environment to Shigella qnrS plasmid pAH0376, but in a
      different environment in the other plasmids. CONCLUSIONS: This is the first
      report of plasmid-mediated quinolone resistance in a Salmonella isolate from the
      UK; five isolates were associated with foreign travel to, or food imported from,
      the Far East. The presence of qnrS1 on different plasmid backbones in several
      Salmonella serotypes suggests successful dissemination of plasmids or qnrS1. It
      is of concern that qnrS1 is being identified in Salmonella serotypes that are
      commonly implicated in human infection in the UK. Coupled with beta-lactam
      resistance, it may compromise treatment of vulnerable patient groups.

PMID- 17434877
TI  - Emergence of a Streptococcus pneumoniae isolate resistant to streptogramins by
      mutation in ribosomal protein L22 during pristinamycin therapy of pneumococcal
      pneumonia.
AB  - OBJECTIVES: The aim of this study was to characterize the mechanism of resistance
      to macrolides and streptogramins of a Streptococcus pneumoniae strain isolated
      from blood cultures in an 80-year-old patient suffering from severe pneumonia
      unsuccessfully treated with pristinamycin. METHODS: Resistance genes erm(B) and
      mef(A) were searched for by PCR. Portions of genes for domains V and II of the
      23S rRNA (rrl) and genes for ribosomal proteins L4 (rplD) and L22 (rplV) were
      amplified by PCR from total genomic DNA and sequenced. RESULTS: Resistance genes
      erm(B) and mef(A) were not detected. Only mutation in the rplV gene encoding
      ribosomal protein L22 was detected. The strain contained a six amino acid
      insertion ((107)KRTAHI(108)) in the C-terminus of the ribosomal protein L22.
      CONCLUSIONS: This is the first report of emergence of a pneumococcus resistant to
      streptogramins by mutation in ribosomal protein L22 during treatment with
      pristinamycin.

PMID- 17434879
TI  - CD4+ T cell evolution and predictors of its trend before and after
      tenofovir/didanosine backbone in the presence of sustained undetectable HIV
      plasma viral load.
AB  - BACKGROUND: Tenofovir with full-dose didanosine has been associated with
      paradoxical CD4 + T cell decrease despite virological suppression. We
      investigated whether tenofovir plus didanosine at a weight-adjusted dosage could
      be responsible for such an effect, and factors associated with CD4 + T cell count
      evolution under this combination. METHODS: This was a prospective observational
      multicohort study (Italian MASTER and Spanish Hospital Carlos III HIV cohorts).
      Patients with HIV plasma viral load suppression for >/= 6 months who switched to
      an antiretroviral combination including tenofovir plus didanosine were studied,
      as long as virological success was maintained. CD4 + T cell count variations over
      time (slopes) were compared before and after switching to tenofovir plus
      didanosine using linear mixed models and segmented regression analysis. RESULTS:
      Annual time-weighted CD4 + T cell count slope did not change significantly after
      the prescription of tenofovir plus didanosine: it was 14 cells/mm(3) [95%
      confidence interval (CI) - 7 to 35] from month - 24 to month - 12, 12 cells/mm(3)
      (95% CI - 14 to 38) from month - 12 to the time of switching, 30 cells/mm(3) (95%
      CI 5-55) from switching to month + 12 and 15 cells/mm(3) (95% CI - 8 to 39) from
      month + 12 to month + 24 after switching to tenofovir plus didanosine. No
      significant change in the slope of the segment after the switch to tenofovir plus
      didanosine-containing regimens when compared with the segment preceding the
      intervention was found (CD4 + T cell count slope change: 24 cells/mm(3); 95% CI -
      10 to 58). Similar results were obtained using CD4 + T cell percentage over total
      lymphocytes. The significant independent predictors of lower CD4 + T cell count
      slope were older age (P = 0.006), lower nadir CD4 + T cell count (P < 0.001) and
      positive hepatitis C virus antibody (P = 0.03). Moreover, reduced estimated
      creatinine clearance was an additional independent predictor of lower CD4 + T
      cell count slope (P = 0.02), but only after excluding nadir CD4 + T cell count.
      CONCLUSIONS: Tenofovir plus didanosine (weight-adjusted dosage) was not
      associated with paradoxical CD4 + T cell decrease in our patients maintaining
      undetectable HIV plasma viral load for a maximum of 24 months after switching.
      Several factors could explain variability in CD4 + T cell count evolution in
      these patients.

PMID- 17434880
TI  - Modified guidelines impact on antibiotic use and costs: duration of treatment for
      pneumonia in a neurosurgical ICU is reduced.
AB  - OBJECTIVES: To evaluate the impact of an intervention to reduce the duration of
      antibiotic treatment for pneumonia in a neurosurgical intensive care unit (ICU).
      The usage of antibiotics and the resultant costs were examined using interrupted
      time series analysis while resistance and device-associated infection rates are
      also described. METHODS: In January 2004, revised guidelines for the use of
      antibiotics were implemented. As a consequence of this, the duration of
      antibiotic therapy for nosocomial pneumonia was reduced from 14 to 7 days, while
      for community-acquired pneumonia the period fell from 10 to 5 days. The effect on
      the antibiotic use density [AD; expressed as defined daily doses (DDD) per 1000
      patient days (pd)] was calculated by segmented regression analysis of interrupted
      time series for the 24 months prior to (2002 and 2003) and after the intervention
      (2004 and 2005). RESULTS: The intervention was associated with a significant
      decrease in total AD from 949.8 to 626.7 DDD/1000 pd after the intervention. This
      was mainly due to reduced consumption of second-generation cephalosporins (-100.6
      DDD/1000 pd), imidazoles (- 100.3 DDD/1000 pd), carbapenems (-33.3 DDD/1000 pd),
      penicillins with beta-lactamase inhibitor (-33.5 DDD/1000 pd) and glycopeptides (
      30.2 DDD/1000 pd). Glycopeptide reduction might be associated with a significant
      decrease in the proportion of methicillin-resistant Staphylococcus aureus (8.4%
      before and 2.9% after the intervention). Similarly, total antibiotic costs/pd
      (Euro) showed a significant decrease from 13.16 Euro/pd before to 7.31 euro/pd
      after the intervention. This is a saving of 5.85 Euro/pd. The incidence of
      patients dying with pneumonia did not change significantly. CONCLUSIONS: The most
      conservative estimate of segmented regression analysis over a 48 month period
      showed that halving the duration of treatment for pneumonia results in a
      reduction of over 30% in antibiotic consumption and costs. Because respiratory
      infections are most common in ICU patients, interventions targeting a reduction
      in the duration of treatment of pneumonia might be extremely worthwhile.

PMID- 17434881
TI  - Correlation of vancomycin and daptomycin susceptibility in Staphylococcus aureus
      in reference to accessory gene regulator (agr) polymorphism and function.
AB  - OBJECTIVES: Recently, an association between the accessory gene regulator (agr)
      in Staphylococcus aureus and the development of vancomycin resistance secondary
      to suboptimal exposure has been demonstrated. We investigated the relationship of
      vancomycin with and without gentamicin or rifampicin, and daptomycin in the
      development of resistance in agr groups I and II. METHODS: S. aureus belonging to
      agr groups I and II was exposed to varying concentrations of vancomycin and
      daptomycin simulating an fAUC/MIC of 14-460 and 30-239, respectively, in an in
      vitro pharmacodynamic model. RESULTS: Vancomycin regimens resulting in fAUC/MIC
      of 16.1-107.0 resulted in resistance in agr I and agr II knockout strains,
      whereas regimens resulting in fAUC/MIC of 16.1 resulted in emergence of
      resistance in agr I- and agr II-positive strains. Overall, agr-null strains
      demonstrated a higher likelihood of resistance and a greater change in vancomycin
      susceptibility. The addition of gentamicin and rifampicin to vancomycin at these
      same exposures prevented the emergence of resistance. At extremely low daptomycin
      exposures of fAUC/MIC of 22-66, an increase in MIC of 2-3-fold up to a maximum of
      0.75 mg/L was observed. However, this was independent of agr group and/or
      function and still within the susceptible range of daptomycin. CONCLUSIONS: The
      combination of vancomycin with either rifampicin or gentamicin prevented the
      emergence of vancomycin resistance in agr I and II S. aureus isolates. Changes in
      daptomycin susceptibility were independent of agr group and function. The
      association between agr and vancomycin resistance in S. aureus requires further
      investigation.

PMID- 17434882
TI  - Drug-eluting stents show delayed healing: paclitaxel more pronounced than
      sirolimus.
AB  - AIMS: To understand wound healing after drug-eluting stents (DES) placement in
      humans, we studied the histology of in-stent restenosis (ISR) tissue obtained by
      atherectomy from bare metal stents (BMS) and DES in comparison with de novo
      atherosclerosis. METHODS AND RESULTS: The tissue was retrieved from ISR in ten
      sirolimus-eluting stents (SES) and nine paclitaxel-eluting stents (PES), six BMS,
      and nine stenotic de novo atherosclerotic lesions and processed for histology and
      immunocytochemistry. Patients with ISR in PES showed a significantly higher
      incidence of unstable angina upon presentation for re-intervention (P = 0.046).
      De novo tissue tended to be more collagen rich, whereas ISR tissue tended to be
      more proteoglycan rich. In all groups, cell content consisted almost exclusively
      of smooth muscle cells. Histology showed that fibrinoid in ISR tissue was present
      only in DES (P = 0.004), as late as 2 years following DES placement, indicating a
      persistent incomplete healing response. The amount of fibrinoid, given as a
      percentage of total tissue in each atherectomy specimen, was greater in PES than
      in SES (17 vs. 5%, P = 0.026). CONCLUSION: ISR in DES shows incomplete neointimal
      healing as late as 2 years after implantation. Patients with ISR in PES presented
      with more unstable angina and showed more pronounced signs of delayed healing
      than SES.

PMID- 17434883
TI  - From altus to parvus: cardiac fatigue in athletes.

PMID- 17434884
TI  - Single-dose depot leuprolide is as efficient as daily short-acting leuprolide in
      ICSI cycles.
AB  - BACKGROUND: In this prospective randomized study, we aimed to compare the
      efficacy of a single depot (1.88 mg) reduced dose with a daily low dose (0.5
      mg/day) of leuprolide for pituitary suppression as part of controlled ovarian
      hyperstimulation (COH) in an ICSI program. METHODS: The study population
      consisted of 103 patients randomized into two groups. Group 1 (n = 52) consisted
      of patients who had daily low-dose leuprolide injections. Group 2 (n = 51)
      consisted of patients who had the 1.88 mg single-dose leuprolide injection.
      RESULTS: The age of the patients, the number of metaphase II oocytes, the number
      and quality of embryos transferred were similar between the two groups. Although
      the length of gonadotrophin stimulation was significantly longer in group 2 (P <
      0.01), the amount of gonadotrophins used was similar (P = 0.34). Leuprolide
      levels were significantly lower in group 2 within the first 8 h after injection
      (P < 0.05), but no difference was observed thereafter. Although LH levels on the
      day of hCG (P = 0.06) administration and estradiol levels on day 3 (P < 0.01)
      were lower in group 2, LH levels and progesterone levels 1 week after embryo
      transfer did not show any statistically significant difference. Clinical
      pregnancy rates per embryo transfer, implantation rates and first trimester
      abortion rates were also similar for both groups. CONCLUSIONS: A single reduced
      depot dose (1.88 mg) of leuprolide was found to be as effective as classical long
      multi-dose protocol for pituitary desensitization in COH for ICSI cycles.

PMID- 17434885
TI  - Commentary: the role of alcohol in mortality differences between European
      countries.

PMID- 17434887
TI  - A bridge to Brugada.
AB  - In acute cardiac care, prompt diagnosis and management is mandatory. The
      electrocardiogram (ECG) remains a crucial investigation in the management of
      ischemic heart disease and arrhythmias. A case is discussed, where the ECG
      changes caused by the Brugada syndrome and those caused by ischemia, aggravated
      by myocardial bridging, intertwine.

PMID- 17434888
TI  - Contemporary catheter ablation of arrhythmias in geriatric patients: patient
      characteristics, distribution of arrhythmias, and outcome.
AB  - AIMS: Catheter ablation is a treatment of first choice for many arrhythmias. Data
      in geriatric patients are still limited, mostly focusing on single arrhythmia
      types. The aim of the study was to investigate characteristics of contemporary
      ablation therapy in the very elderly, focusing on patient characteristics,
      arrhythmia spectrum, and outcome in a large cohort. METHODS AND RESULTS: We
      studied 131 consecutive patients aged 80 and older (mean age 83 +/- 3) undergoing
      ablation for any indication from 1998 until 2004. Sixty-eight patients (52%) had
      structural heart disease. Most common indications were typical atrial flutter
      (54%), atrioventricular nodal re-entrant tachycardia (AVNRT) (22%), and atrial
      fibrillation (AF) (18%). Patients with structural heart disease had more often
      atrial flutter (72 vs. 35%, P < 0.001) and less AVNRT (7 vs. 38%, P < 0.001) than
      those without structural heart disease. In almost all patients with AF,
      ventricular rate control was achieved by elimination of atrioventricular
      conduction and pacemaker implantation. Success rate exceeded 97% for all ablation
      types. There was one major complication (0.8%), a stroke after isthmus ablation.
      CONCLUSION: Almost half of the very elderly patients undergoing ablation have
      structural heart disease. Indications have changed significantly in recent years,
      typical atrial flutter is nowadays the predominant indication. The arrhythmia
      spectrum differs significantly between patients with and without structural heart
      disease. Regardless of the presence or absence of structural heart disease,
      success is excellent. Catheter ablation is an excellent therapy option for
      geriatric patients with arrhythmias.

PMID- 17434889
TI  - Value of CT localization of the fossa ovalis prior to transseptal left heart
      catheterization for left atrial ablation.
AB  - AIMS: Transseptal puncture (TP) can be a difficult procedure and is not without
      risk of complications. The purpose of this study was to evaluate the use of three
      dimensional multi-detector row computed tomography (MDCT) to localize the fossa
      ovalis (FO) and facilitate TP in patients undergoing left atrial catheter
      ablation. METHODS AND RESULTS: Fourteen consecutive patients were studied.
      Thirteen patients underwent pulmonary vein isolation and one patient had ablation
      for left atrial flutter. All patients underwent cardiac MDCT imaging pre-ablation
      for use in conjunction with electroanatomic mapping. Prior to puncturing the
      interatrial septum, standard fluoroscopic views of the transseptal sheath were
      compared with corresponding MDCT images tagging the FO. Successful, uncomplicated
      TP was achieved in all 14 patients. The mean duration of TP was 15.6 +/- 10.0
      min. The average fluoroscopy time was 8.5 +/- 7.4 min. The MDCT images were
      deemed helpful in facilitating TP in 13 patients (93%). CONCLUSION: This study
      demonstrates the feasibility of MDCT to localize the FO and aid TP. For patients
      undergoing left atrial ablation in whom MDCT imaging is undertaken pre-ablation,
      tagging the FO can be easily performed and is a novel tool for guiding
      transseptal catheterization without additional risk.

PMID- 17434890
TI  - Acute biventricular pacing after cardiac surgery has no influence on regional and
      global left ventricular systolic function.
AB  - BACKGROUND: Cardiac resynchronization therapy has been shown to improve systolic
      function in patients with advanced chronic heart failure and electromechanical
      delay (QRS width > 120 ms). However, the effect of acute biventricular (BiV)
      pacing on perioperative haemodynamic changes is not well defined. In the present
      study, acute changes in regional left ventricular (LV) systolic function
      determined by tissue Doppler imaging (TDI) and global LV systolic function
      determined by the continuous cardiac output method were measured during various
      pacing configurations in patients with depressed LV systolic function undergoing
      heart surgery. METHODS: Twenty-six patients (age 68 +/- 8 years, 15 males) with
      depressed systolic LV function (LV ejection fraction <or=35%), symptomatic heart
      failure, and a QRS duration of > 120 ms undergoing temporary epicardial BiV
      pacing after aortocoronary bypass and valve surgery were included. QRS duration
      on surface electrocardiogram (ECG), TDI (systolic velocities of septal and
      lateral mitral annulus), cardiac index (CI), right atrial pressure, pulmonary
      artery pressure (PAP), and pulmonary capillary wedge pressure (PCW) were measured
      during various pacing configurations [no pacing (intrinsic rhythm), right atrial
      biventricular (RA-BiV pacing), right atrial-left ventricular (RA-LV), right
      atrial-right ventricular (RA-RV), and AAI pacing]. RESULTS: There were no
      differences in QRS duration during intrinsic rhythm, RA-BiV pacing, and AAI
      pacing. However, RA-LV and RA-RV stimulations showed a longer QRS duration (P <
      0.01 vs. intrinsic rhythm, RA-BiV pacing, and AAI, respectively). Tissue Doppler
      velocities of the septal and lateral mitral annulus were comparable in all pacing
      modes. Neither CI nor PAP or PCW showed significant differences during the
      various pacing configurations. There was a positive correlation between regional
      (TDI) and global (CI) parameters of LV systolic function. Conclusions
      Biventricular pacing after heart surgery does not improve parameters of regional
      and global LV systolic function acutely in patients with heart failure and
      intraventricular conduction delay and, thus, may not reflect changes observed
      with chronic BiV pacing.

PMID- 17434891
TI  - Type-D personality but not implantable cardioverter-defibrillator indication is
      associated with impaired health-related quality of life 3 months post
      implantation.
AB  - AIMS: Little is known about the impact of ICD indication (primary vs. secondary)
      on health-related quality of life (HRQL). Indication may also interact with
      psychological factors, such as personality. Using a prospective design, we
      examined whether ICD indication and type-D personality (i.e. experiencing
      increased negative emotions paired with emotional non-expression) serve as
      modulators of HRQL at baseline and 3 months post-implantation. METHODS AND
      RESULTS: Consecutively implanted ICD patients (n = 154) completed the Type-D
      Scale (DS14) at baseline and the Short-Form Health Survey 36 (SF-36) at baseline
      and 3 months. Of all patients, 82 (53%) received an ICD due to prophylactic
      reasons; the prevalence of type-D was 23%. Indication had no influence on HRQL (P
      = 0.75). Further stratification by personality showed a main effect for type-D
      personality (P < 0.001), with type-D patients generally experiencing poorer HRQL;
      there was no main effect for indication (P = 0.45) nor was the interaction effect
      indication by type-D significant (P = 0.22). There was a significant improvement
      in HRQL over time (P = 0.001). Type-D remained an independent predictor of
      impaired HRQL, adjusting for clinical factors and shocks during follow-up (P <
      0.001). However, in adjusted analysis there was no longer a significant change in
      HRQL over time (P = 0.099). CONCLUSION: Type-D personality but not ICD indication
      was associated with impaired HRQL at the time of implantation and at 3 months. In
      the quest for enhancing risk stratification in clinical practice, personality
      factors, such as type-D, should not be ignored, as both type-D and poor HRQL have
      been associated with increased risk of mortality in cardiac patients.

PMID- 17434892
TI  - Analysis of terminal arrhythmias stored in the memory of pacemakers from patients
      dying suddenly.
AB  - AIMS: Stored electrograms or marker channels are available in most of modern
      cardiac pacemaker models. We sought to analyse these information to uncover
      terminal events of pacemaker patients dying suddenly. Method and results We made
      post-mortem pacemaker (PM) interrogations in 19 patients dying suddenly out of
      hospital between the years 1997 and 2005 (mean age 59 +/- 13 years, 90% males).
      The systems had activated arrhythmia monitoring algorithms. Indications of pacing
      were sick sinus syndrome in seven, AV-block in five, and heart failure due to
      asynchrony in seven cases. The interrogated pacemakers were CHORUS 7034 (n = 12),
      CONTAK TR (n = 2), and INSYNC III (n = 5). For interpretation stored marker
      channels and electrograms were analysed. The mean observation time after PM
      implantation prior death was 2.11 +/- 1.44 years, the mean left ventricular
      ejection fraction from the last available echo examination in the year prior
      death was 27.5 +/- 8%, mean age was 63 +/- 12 years. In 17/19 cases (89%), a
      tachycardia (most likely ventricular tachycardia) was found correlating to the
      time of death. The mean cycle length of the terminal arrhythmia was 307 +/- 144
      (250-344) ms, corresponding to a heart rate of 195 +/- 95 (174-240) bpm. We found
      no evidence of specific pacemaker-related problems such as electronic failure,
      battery depletion, or undersensing. CONCLUSIONS: Post-mortem analysis of
      arrhythmia monitoring of pacemaker patients revealed tachycardias (most likely
      ventricular tachycardia) to be related to sudden death. These findings give some
      insight in mechanisms of terminal events in this group.

PMID- 17434893
TI  - Targeted therapy in nuclear medicine--current status and future prospects.
AB  - In recent years, a number of new developments in targeted therapies using
      radiolabeled compounds have emerged. New developments and insights in radioiodine
      treatment of thyroid cancer, treatment of lymphoma and solid tumors with
      radiolabeled monoclonal antibodies (mAbs), the developments in the application of
      radiolabeled small receptor-specific molecules such as meta-iodobenzylguanidine
      and peptides and the position of locoregional treatment in malignant involvement
      of the liver are reviewed. The introduction of recombinant human thyroid
      stimulating hormone and the possibility to enhance iodine uptake with retinoids
      has changed the radioiodine treatment protocol of patients with thyroid cancer.
      Introduction of radiolabeled mAbs has provided additional treatment options in
      patients with malignant lymphoma, while a similar approach proves to be
      cumbersome in patients with solid tumors. With radiolabeled small molecules that
      target specific receptors on tumor cells, high radiation doses can be directed to
      tumors in patients with disseminated disease. Radiolabeled somatostatin
      derivatives for the treatment of neuroendocrine tumors are the role model for
      this approach. Locoregional treatment with radiopharmaceuticals of patients with
      hepatocellular carcinoma or metastases to the liver may be used in inoperable
      cases, but may also be of benefit in a neo-adjuvant or adjuvant setting.
      Significant developments in the application of targeted radionuclide therapy have
      taken place. New treatment modalities have been introduced in the clinic. The
      concept of combining therapeutic radiopharmaceuticals with other treatment
      modalities is more extensively explored.

PMID- 17434894
TI  - The expanding role of PET technology in the management of patients with
      colorectal cancer.
AB  - The therapeutic options and subsequent survival of colorectal cancer (CRC)
      patients has increased substantially over recent years. While surgical excision
      of the primary cancer results in cure of approximately 50% of patients,
      recurrence and metastatic disease still remains a significant cause of death.
      Although resection of liver or lung metastases can result in cure, relapse rates
      remain high, indicating that patient selection needs improvement. Positron
      emission tomography (PET) technology has a great deal to offer with respect to
      CRC management, particularly in the setting of patient selection for
      metastasectomy and in the evaluation of possible recurrent disease, however it
      has not yet become a routine part of the management of all CRC patients. This
      review article aims to discuss the current and future implications of PET
      technology in the optimal management of CRC patients throughout their care
      pathway.

PMID- 17434895
TI  - The effect of short-term intensive chemotherapy on reactivation of tuberculosis.
AB  - BACKGROUND: Various malignancies and cytotoxic chemotherapy have been proposed to
      increase the risk of reactivation of tuberculosis. Available literature to
      support this observation is still conflicting. There is scarcity of data from
      countries with rampant tubercular infection, such as India, in this regard.
      DESIGN AND METHODS: In the present retrospective analysis, patients with high
      grade non-Hodgkin's lymphoma with past history of tuberculosis and have had
      adequate antitubercular therapy were identified from a Lymphoma Group study.
      These patients were followed up during cytotoxic chemotherapy and later to assess
      the risk of reactivation. RESULTS: A cohort of eight patients with past history
      of tuberculosis was selected from 141 patients of high-grade non-Hodgkin's
      lymphoma. The median age was 33.5 years (range, 24-53 years). Median duration
      between completion of antitubercular treatment and diagnosis of lymphoma was 5
      years (range, 1.5-10 years). All patients received cyclical cytotoxic
      chemotherapy. The median duration of follow up after completion of chemotherapy
      was 5 years (range, 10 months to 5 years). None of these patients developed
      reactivation of tuberculosis. CONCLUSION: Cyclical chemotherapy for non-Hodgkin's
      lymphoma does not lead to reactivation of tuberculosis.

PMID- 17434896
TI  - Effect of subcentimeter nonpositive resection margin on hepatic recurrence in
      patients undergoing hepatectomy for colorectal liver metastases. Evidences from
      663 liver resections.
AB  - OBJECTIVE: To elucidate if a nonpositive <1-cm resection margin has any effect on
      hepatic recurrence in patients undergoing liver resection for colorectal liver
      metastases. PATIENTS AND METHODS: Six hundred and nine patients underwent 663
      liver resections. Patients with positive margin were excluded from the analysis.
      Two groups were studied: group A, <1-cm resection margin and group B, > or =1-cm
      resection margin. RESULTS: A total of 545 liver resections in 523 patients were
      carried out with nonpositive resection margins. With a median follow-up of 25
      months, the 5-year cumulative hepatic recurrence reached 54% in group A (n = 206)
      and 41% in group B (n = 339). Factors associated with hepatic recurrence were
      synchronic metastases (P = 0.0015), bilobar (P < 0.001), two or more metastases
      (P < 0.001), margin <1 cm (P = 0.0123) and extrahepatic disease (P = 0.0037). A
      strong correlation between resection margin and number of metastases was
      confirmed (P < 0.001). At multivariate analysis only two factors were independent
      predictors of hepatic recurrence: multinodular disease in the liver specimen [>
      or =4 metastases hazard ratio (HR) = 3.45; 95% confidence interval (CI): 2.2
      5.38; P < 0.001] and extrahepatic disease at hepatectomy (HR = 1.58; 95% CI: 1.58
      3.32). CONCLUSION: Subcentimeter nonpositive resection margins do not directly
      influence hepatic recurrence in patients undergoing hepatectomy for colorectal
      liver metastases.

PMID- 17434897
TI  - Reducing by half the percentage of late-stage presentation for breast and cervix
      cancer over 4 years: a pilot study of clinical downstaging in Sarawak, Malaysia.
AB  - BACKGROUND: The registry of the Oncology Departmental in Sarawak General Hospital
      showed that 79% of nasopharyngeal, 77% of breast and 70% of cervix cancer
      patients were diagnosed at an advanced stage (stages III and IV) for year 1993.
      Hence, a low cost Early Cancer Surveillance Program was started in 1994, with the
      intent of downstaging these three most common cancers in Sarawak. MATERIALS AND
      METHODS: The program consisted of (i) training health staff in hospital and rural
      clinics to improve their skills in early cancer detection, (ii) raising public
      awareness through pamphlets, posters and sensitization by health staff. RESULTS:
      Data analysis revealed that the program achieved downstaging in two of the
      cancers. Breast cancer in stage III and IV was reduced from 60% (1994) to 35%
      (1998) (P < 0.0001) and cervical cancer in stage III and IV from 60% (1994) to
      26% (1998) (P < 0.0001). No reduction was observed for nasopharyngeal cancer at
      88% (1994) to 91% (1998). CONCLUSIONS: The overall cost of this program was
      <US$34 000. It is cost-effective and easy to implement and would be a valuable
      alternative in countries where majority of the tumors are found in late stage
      (III and IV) where screening programs meet important difficulties. Our data
      analyses revealed important shortcomings in the PAP smear screening program where
      inadequate groups of women were screened. It resulted in a pick up rate of only
      5% of the cases. This finding confirmed the need for the simple and complementary
      downstaging approach.

PMID- 17434898
TI  - Up-to-date survival estimates and historical trends of cutaneous malignant
      melanoma in the south-east of The Netherlands.
AB  - BACKGROUND: We present survival outcomes of patients registered in the Dutch
      population-based Eindhoven Cancer Registry (ECR). PATIENTS AND METHODS: Data on
      patients diagnosed with a melanoma between 1980 and 2002 were obtained from the
      ECR. Data on vital status up to 1 January 2005 were obtained, up-to-date survival
      rates were calculated using period analysis. Multivariate analyses were carried
      out using Cox proportional hazards model. RESULTS: Ten-year crude survival rates
      were 82% for women and 60% for men (P < 0.05). Thin melanomas (Breslow thickness
      <or= 2.0 mm) had 5-year crude survival rates >74%, for melanomas >4.0 mm these
      rates were <65% (P < 0.05). In the early 1980s, 5-year relative survival rates
      were 84% and 62% for young (<60 years) women and men, and 66% and 69%,
      respectively, for the elderly (aged 60+). In the period 2000-2002, these rates
      had improved to >90% for females and to >72% for males. Multivariate analyses
      showed increased hazard ratios with increasing age and Breslow thickness, being
      male, having a melanoma on the trunk or unknown sites and having a nodular
      melanoma. CONCLUSIONS: Despite the absence of improvements in treatment options
      for melanoma, survival improved significantly, except for elderly males.

PMID- 17434900
TI  - Bevacizumab in a growing teratoma syndrome. Case report.

PMID- 17434899
TI  - Randomized phase II study of docetaxel plus estramustine and single-agent
      docetaxel in patients with metastatic hormone-refractory prostate cancer.
AB  - BACKGROUND: Docetaxel (Taxotere)-based regimens are the new standard therapy in
      advanced hormone-refractory prostate cancer (HRPC). A synergistic activity has
      been shown with docetaxel in combination with estramustine in vitro; however, the
      benefit of this combination remains controversial in clinical practice. We
      assessed the activity and safety of docetaxel alone and docetaxel-estramustine in
      HRPC. PATIENTS AND METHODS: Patients (n = 92) with metastatic HRPC and rising
      prostate-specific antigen (PSA) while receiving androgen suppression were
      randomized to 3-weekly treatment with either docetaxel 75 mg/m(2), day 1 (D), or
      docetaxel 70 mg/m(2), day 2, plus oral estramustine 280 mg twice daily, days 1-5
      (DE). RESULTS: Ninety-one patients were treated (DE 47, D 44). A PSA response
      occurred in 68% (primary endpoint met) and 30% of patients, respectively. Median
      PSA response duration was 6.0 months in both groups. Median time to progression
      was 5.7 and 2.9 months, and median survival was 19.3 and 17.8 months in the DE
      and D arms, respectively. Hematologic and non-hematologic toxic effects were mild
      and similar in both arms. One patient in each group withdrew due to toxicity.
      Quality of life was similar in both groups. CONCLUSION: Combining estramustine
      with docetaxel in this schedule is an active and well-tolerated treatment option
      in HRPC.

PMID- 17434901
TI  - Opposite evolutionary effects between different alternative splicing patterns.
AB  - Alternative splicing (AS) has been recognized as a mechanism of relaxing
      selection pressure on protein subsequences. Here, we show that AS may also yield
      contrary evolutionary effects. We compare the evolutionary rates of 2 types of
      alternatively spliced exons (ASEs)-simple and complex. The former does not change
      the boundaries of its flanking exons, whereas the latter does. By analyzing over
      26,000 human-mouse orthologous exons, we demonstrate that complex ASEs have lower
      Ka and Ka/Ks ratio and higher Ks than constitutively spliced exons (CSEs),
      whereas simple ASEs have evolutionary rates to the opposite of CSEs. Our results
      indicate that complex ASEs are subject to stronger selection pressure than CSEs
      at the protein level, but the trend is reversed at the RNA level. Therefore, the
      previous view that ASEs accelerate evolution of protein subsequences needs to be
      modified.

PMID- 17434902
TI  - Gene order and recombination rate in homologous chromosome regions of the chicken
      and a passerine bird.
AB  - Genome structure has been found to be highly conserved between distantly related
      birds and recent data for a limited part of the genome suggest that this is true
      also for the gene order (synteny) within chromosomes. Here, we confirm that
      synteny is maintained for large chromosomal regions in chicken and a passerine
      bird, the great reed warbler Acrocephalus arundinaceus, with few rearrangements,
      but in contrast show that the recombination-based linkage map distances differ
      substantially between these species. We assigned a chromosomal location based on
      sequence similarity to the chicken genome sequence to a set of microsatellite
      loci mapped in a pedigree of great reed warblers. We detected homologous loci on
      14 different chromosomes corresponding to chicken chromosomes Gga1-5, 7-9, 13,
      19, 20, 24, 25, and Z. It is known that 2 passerine macrochromosomes correspond
      to the chicken chromosome Gga1. Homology of 2 different great reed warbler
      linkage groups (LG13 and LG5) to Gga1 allowed us to locate the split to a
      position between 20.8 and 84.8 Mb on Gga1. Data from the 5 chromosomal regions
      (on Gga1, 2, 3, 5, and Z) with 3 or more homologous loci showed that synteny was
      conserved with the exception of 2 large previously unreported inversions on
      Gga1/LG5 and Gga2/LG3, respectively. Recombination data from the 9 chromosomal
      regions in which we identified 2 or more homologous loci (accounting for the
      inversions) showed that the linkage map distances in great reed warblers were
      only 6.3% and 13.3% of those in chickens for males and females, respectively.
      This is likely to reflect the true interspecific difference in recombination rate
      because our markers were not located in potentially low-recombining regions:
      several linkage groups covered a substantial part of their corresponding chicken
      chromosomes and were not restricted to centromeres. We conclude that
      recombination rates may differ strongly between bird species with highly
      conserved genome structure and synteny and that the chicken linkage map may not
      be suitable, in terms of genetic distances, as a model for all bird species.

PMID- 17434903
TI  - Glass sponges and bilaterian animals share derived mitochondrial genomic
      features: a common ancestry or parallel evolution?
AB  - Glass sponges (Hexactinellida) are a group of deep-water benthic animals that
      have a unique syncytial organization and possess a characteristic siliceous
      skeleton. Although hexactinellids are traditionally grouped with calcareous and
      demosponges in the phylum Porifera, the monophyly of sponges and the phylogenetic
      position of the Hexactinellida remain contentious. We determined and analyzed the
      nearly complete mitochondrial genome sequences of the hexactinellid sponges
      Iphiteon panicea and Sympagella nux. Unexpectedly, our analysis revealed several
      mitochondrial genomic features shared between glass sponges and bilaterian
      animals, including an Arg --> Ser change in the genetic code, a characteristic
      secondary structure of one of the serine tRNAs, highly derived tRNA and rRNA
      genes, and the presence of a single large noncoding region. At the same time,
      glass sponge mtDNA contains atp9, a gene previously found only in the mtDNA of
      demosponges (among animals), and encodes a tRNA(Pro);(UGG) with an atypical A11
      U24 pair that is also found in demosponges and placozoans. Most of our sequence
      based phylogenetic analyses place Hexactinellida as the sister group to the
      Bilateria; however, these results are suspect given accelerated rates of
      mitochondrial sequence evolution in these groups. Thus, it remains an open
      question whether shared mitochondrial genomic features in glass sponges and
      bilaterian animals reflect their close phylogenetic affinity or provide a
      remarkable example of parallel evolution.

PMID- 17434904
TI  - Parents sharing books with young deaf children in spoken english and in BSL: the
      common and diverse features of different language settings.
AB  - Twelve parents of young deaf children were recorded sharing books with their deaf
      child--six from families using British Sign Language (BSL) and six from families
      using spoken English. Although all families were engaged in sharing books with
      their deaf child and concerned to promote literacy development, they approached
      the task differently and had different expectations in terms of outcome. The sign
      bilingual families concentrated on using the book to promote BSL development,
      engaging in discussion around the book but without referring to the text, whereas
      the spoken language families were focused on features of the text and less
      inclined to use the book to promote wider knowledge. Implications for early
      intervention and support are drawn from the data.

PMID- 17434905
TI  - Bone formation markers in adults with mild osteogenesis imperfecta.
AB  - BACKGROUND: Plasma concentrations of procollagen peptides are decreased in
      osteogenesis imperfecta (OI), whereas other bone formation markers may be
      increased. We examined the utility of combining these markers in the diagnosis of
      OI in adults. METHODS: We measured plasma concentrations of procollagen-1 N
      peptide (P1NP), osteocalcin, and bone alkaline phosphatase in 24 patients with
      nondeforming OI, 25 patients with low bone mass due to other causes, and 38 age-
      and sex-matched controls. The discriminant ability of various test combinations
      was assessed by the construction of ROC curves. RESULTS: The median (range) ratio
      of osteocalcin to P1NP was significantly greater in patients with type I OI [1.75
      (0.80-3.86)] than in controls [0.59 (0.34-0.90)] and patients with other causes
      of low bone mass [0.48 (0.05-1.38); P <0.0001]. This ratio allowed nearly
      complete differentiation between healthy controls and patients with type I OI,
      but not patients with type IV OI. With a cutoff of 0.97 for osteocalcin:P1NP, the
      sensitivity and specificity were maximized at 95% (95% CI 76%-100%) and 88% (69%
      97%), respectively, for patients with other causes of low bone mass vs those with
      type I OI only. For patients with other causes of low bone mass vs all OI
      patients, sensitivity and specificity were 83% (63%-95%) and 88% (69%-97%),
      respectively. The addition of bone alkaline phosphatase data did not improve the
      discriminant ability of the osteocalcin:P1NP ratio. CONCLUSIONS: The
      osteocalcin:P1NP ratio is a sensitive and specific test for type I OI in adults,
      but it has less utility in the diagnosis of other types of nondeforming OI.

PMID- 17434906
TI  - Biosensor analysis of beta2-glycoprotein I-reactive autoantibodies: evidence for
      isotype-specific binding and differentiation of pathogenic from infection-induced
      antibodies.
AB  - BACKGROUND: For the laboratory diagnosis of the antiphospholipid syndrome (APS)
      we developed a biosensor with the ability to distinguish between disease-relevant
      anti-beta2-glycoprotein I (beta2GPI) autoantibodies (anti-beta2GPI) and pathogen
      specific beta2GPI cross-reactive antibodies that occur transiently during
      infections. METHODS: We used a surface plasmon resonance (SPR) biosensor device.
      For the detection of anti-beta2GPI in serum samples, affinity-purified human
      beta2GPI was covalently attached to a functionalized n-alkanethiol self
      assembling monolayer on the biosensor chip. After verifying the specificity of
      the biosensor system with a panel of monoclonal antibodies to beta2GPI, we
      analyzed sera from healthy donors and patients suffering from APS, systemic lupus
      erythematosus (SLE), syphilis, or parvovirus B19 infections. The SPR results were
      compared with beta2GPI-specific ELISA. RESULTS: Using the SPR biosensor, we
      recorded antigen binding curves with response levels in the range of 50-500,
      resonance units (RU) for anti-beta2GPI ELISA-positive APS patient sera. The
      amplitudes of the antiphospholipid antibody (APL) responses in the biosensor
      correlated with the overall IgG and IgM anti-beta2GPI ELISA titers with a
      correlation coefficient of 0.87. Moreover, we observed immunoglobulin isotype
      specific association and dissociation profiles for APL binding of different APS
      patient sera to the biosensor-immobilized beta2GPI. In contrast to APS patient
      samples, no significant anti-beta2GPI binding (response levels <35 RU) was
      observed in samples from healthy individuals or from patients suffering from SLE,
      syphilis, or parvovirus B19 infection. CONCLUSIONS: The SPR biosensor system
      enables specific detection of APS-associated beta2GPI-reactive APL and
      differentiation from beta2GPI cross-reactive antibodies that occur frequently
      during acute infections. The established association/dissociation plot for anti
      beta2GPI responses in APS patient sera gives additional information regarding the
      influence of anti-beta2GPI IgG and IgM isotype distribution.

PMID- 17434907
TI  - Effects of storage, RNA extraction, genechip type, and donor sex on gene
      expression profiling of human whole blood.
AB  - BACKGROUND: Gene expression profiling of whole blood may be useful for monitoring
      toxicological exposure and for diagnosis and monitoring of various diseases.
      Several methods are available that can be used to transport, store, and extract
      RNA from whole blood, but it is not clear which procedures alter results. In
      addition, characterization of interindividual and sex-based variation in gene
      expression is needed to understand sources and extent of variability. METHODS:
      Whole blood was obtained from adult male and female volunteers (n = 42) and
      stored at various temperatures for various lengths of time. RNA was isolated and
      RNA quality analyzed. Affymetrix GeneChips (n = 23) were used to characterize
      gene expression profiles (GEPs) and to determine the effects on GEP of storage
      conditions, extraction techniques, types of GeneChip, or donor sex. Hierarchical
      clustering and principal component analysis were used to assess interindividual
      differences. Regression analysis was used to assess the relative impact of the
      studied variables. RESULTS: Storage of blood samples for >1 week at 4 degrees C
      diminished subsequent RNA quality. Interindividual GEP differences were seen, but
      larger effects were observed related to RNA extraction technique, GeneChip, and
      donor sex. The relative importance of the variables was as follows: storage <
      genechip < extraction technique < donor sex. CONCLUSION: Sample storage and
      extraction methods and interindividual differences, particularly donor sex,
      affect GEP of human whole blood.

PMID- 17434908
TI  - Quality-controlled measurement methods for quantification of variations in
      transcript abundance in whole blood samples from healthy volunteers.
AB  - BACKGROUND: Transcript abundance (TA) measurement in whole blood frequently is
      conducted to identify potential biomarkers for disease risk and to predict or
      monitor drug response. Potential biomarkers discovered in this way must be
      validated by quantitative technology. In this study we assessed the use of
      standardized reverse transcription PCR (StaRT-PCR) to validate potential
      biomarkers discovered through whole blood TA profiling. METHODS: For each of 15
      healthy volunteers, 6 blood samples were obtained, including 3 samples at each of
      2 separate visits. Total variation in TA for each gene was partitioned into
      replicate, sample, visit, study participant, and residual components. RESULTS:
      Variation originating from technical processing was <5% of total combined
      variation and was primarily preanalytical. Interindividual biological sample
      variation was larger than technical variation. For 12 of 19 tests, the
      distribution of measured values was gaussian (Shapiro-Wilks test). CONCLUSION:
      For control or diseased population groups with variation rates as low as those
      observed in this control group, 17 individuals per group would be required to
      detect 1 SD change with 80% power with a 2-sided alpha = 0.05 statistical test
      for mean differences.

PMID- 17434909
TI  - Evaluation of a 1,25-dihydroxyvitamin D enzyme immunoassay.
AB  - BACKGROUND: Radioactive reagents are used in most assays for measurement of 1,25
      dihydroxyvitamin D [1,25(OH)(2)D]. We evaluated a 1,25(OH)(2)D enzyme immunoassay
      (EIA) from IDS Ltd. that uses solid-phase immunoextraction and colorimetric
      detection and compared results to those of the thymus radioreceptor assay (RRA)
      for 1,25(OH)(2)D. METHODS: We collected serum samples (n = 145) representing an
      even distribution (0-200 pmol/L) of 1,25(OH)(2)D concentrations and Vitamin D
      External Quality Assessment Scheme (DEQAS) proficiency survey samples from 2004
      surveys (n = 15) and stored them at -20 degrees C. We analyzed all samples with
      both EIA and RRA methods. We calculated imprecision using 5 QC samples in
      quadruplicate in each run (n = 6), including both pooled patient material used
      for QC with the RRA and QC material included in the EIA reagent set. We evaluated
      calibration stability by analyzing calibrators from different lots on the same
      plate and determining if calculated sample values drifted significantly. RESULTS:
      Deming linear regression between IDS EIA and RRA methods yielded slope 1.25 (95%
      CI 1.13-1.37), y-intercept -3 (95% CI -18 to 12), R(2) = 0.74. DEQAS proficiency
      survey samples for 2004 were all within 30% of the all-methods-trimmed mean.
      Imprecision CVs were 12%-16% within-run and 15%-20% between-run. CONCLUSIONS: We
      find no evidence of inferiority to the classic calf-thymus receptor assay for
      1,25(OH)(2)D and no disadvantage in the results generated by the IDS EIA using
      samples from the major proficiency survey for 1,25(OH)(2)D. According to the
      product insert, however, the IDS EIA underestimates 1,25(OH)(2)D(2) compared with
      the D(3) form.

PMID- 17434910
TI  - Anti-CCP antibody testing as a diagnostic and prognostic tool in rheumatoid
      arthritis.
AB  - Rheumatoid arthritis is both common and chronic, with significant consequences
      for multiple organ systems. Better understanding of its pathophysiology has led
      to the development of targeted therapies that have dramatically improved
      outcomes. The key to therapeutic success lies in identifying individuals who will
      have severe destructive disease as early as possible, so that effective treatment
      can be initiated before irreversible damage occurs. Anti-cyclic citrullinated
      peptide (anti-CCP) antibody testing is particularly useful in the diagnosis of
      rheumatoid arthritis, with high specificity, presence early in the disease
      process, and ability to identify patients who are likely to have severe disease
      and irreversible damage. However, its sensitivity is low, and a negative result
      does not exclude disease. Anti-CCP antibodies have not been found at a
      significant frequency in other diseases to date, and are more specific than
      rheumatoid factor for detecting rheumatoid arthritis. We discuss anti-CCP
      antibody testing in rheumatoid arthritis, with an emphasis on diagnostic
      performance, prognostic capability, and relevance to pathogenesis and new
      treatment paradigms in rheumatoid arthritis.

PMID- 17434911
TI  - High levels of N-terminal pro B-type natriuretic peptide are associated with ST
      resolution failure after reperfusion for acute myocardial infarction.
AB  - BACKGROUND: B-type natriuretic peptide and the N-terminal fragment of its
      prohormone, N-terminal pro-brain natriuretic peptide (Nt-proBNP), provide
      valuable prognostic information on short- and long-term mortality in patients
      with acute coronary syndrome AIM: To investigate the association between plasma
      NT-proBNP levels and ST-segment resolution (STR) after reperfusion in patients
      with ST-segment elevation myocardial infarction (STEMI). METHODS: Consecutive
      patients from the French regional RICO survey with STEMI who were treated by
      primary PCI or lysis <12 h were included. Blood sample was taken on admission to
      measure plasma NT-proBNP. Maximal ST segment elevation was measured on the single
      worst ECG lead before and 90 min after reperfusion. Patients were categorized as
      STR(-) (<50% STR) or STR(+) (>or=50% STR). RESULTS: Of the 486 patients included,
      133 (27%) were STR(-). STR(-) patients had similar cardiovascular risk factors
      but higher in-hospital mortality (5% vs. 1%, p=0.03) than STR(+) patients. The
      STR(-) group had higher median (IQR) levels of Nt-proBNP: 938 (211-3272) vs. 533
      (169-1471) pg/ml, p=0.003. On multivariate analysis, the highest quartile of Nt
      ProBNP, Q waves and lysis were independent risk factors for incomplete STR.
      DISCUSSION: Our data show a strong association between high levels of Nt-proBNP
      at admission and incomplete STR, suggesting that Nt-proBNP may be useful for
      early risk stratification in reperfusion therapy after acute myocardial
      infarction.

PMID- 17434912
TI  - Misdiagnosis of pulmonary embolism.

PMID- 17434913
TI  - Diacylglycerol oil for apolipoprotein C-II deficiency.

PMID- 17434914
TI  - Cross-sample entropy statistic as a measure of complexity and regularity of renal
      sympathetic nerve activity in the rat.
AB  - In this study, we employed both power spectral analysis and cross-sample entropy
      measurement to assess the relationship between two time series, arterial blood
      pressure (ABP) and renal sympathetic nerve activity (RSNA), during a mild
      haemorrhage in anaesthetized Wistar rats. Removal of 1 ml of venous blood
      decreased BP (by 7.1 +/- 0.7 mmHg) and increased RSNA (by 25.9 +/- 2.4%). During
      these changes, the power in the RSNA signal at heart rate frequency was reduced
      but coherence between the spectra at heart rate frequency in RSNA and ABP
      remained unchanged. Cross-sample entropy was significantly increased (by 10%) by
      haemorrhage, revealing that there was greater asynchrony between ABP and the RSNA
      time series. Intrathecal administration of the glutamate receptor antagonist
      kynurenic acid (2 mm) almost halved (P < 0.01) the reflex increase in RSNA. Also
      during kynurenic acid block, haemorrhage failed to change total power, power at
      heart rate frequency, coherence at heart rate frequency, or the cross-sample
      entropy measurements. We conclude that the increase in asynchrony between ABP and
      RSNA during the reflex increase in RSNA was a consequence of an increase in
      synaptic input to the spinal renal neurones. The data show that the cross-sample
      entropy calculations can characterize the non-linearities of neural mechanisms
      underlying cardiovascular control and have a potential to reveal how some aspects
      of homeostatic regulation of kidney function is achieved by the autonomic nervous
      system.

PMID- 17434915
TI  - The relationships between plasma potassium, muscle excitability and fatigue
      during voluntary exercise in humans.
AB  - The relationships between extracellular potassium elevation and EMG variables in
      relation to muscle fatigue were investigated during handgrip exercise in humans.
      Acid-base state, lactate, potassium ([K+](v)) and sodium in venous plasma, as
      well as variables of surface voluntary and evoked (M-wave) EMG were determined
      during repeated dynamic (DE) and static (SE) exercise (1 min exercise, 4 min
      rest). The different rises of [K+](v) were induced by randomly varied workloads.
      After 15 min of warming up, the M-wave area increased to 124.9 +/- 19.6% (P <
      0.001) in comparison with the control value. Simultaneously, the [K+](v)
      decreased from 4.1 +/- 0.3 to 3.6 +/- 0.3 mmol l(-1) (P < 0.01). During both SE
      and DE, there were marked intensity-dependent signs of fatigue. The [K+](v)
      correlated with changes of the integrated EMG (r = 0.87, P < 0.001 for both DE
      and SE). Changes in the M-wave area during the exercise bouts correlated
      inversely with the [K+](v) (r = -0.73, P < 0.001). The M-wave area did not
      decrease below the control value at any intensity. The median frequency of the
      EMG decreased during exercise, depending on the exercise intensity (r = -0.73 for
      SE, r = -0.47 for DE, P < 0.001) with a maximal decrease to about 80% after SE
      with the maximal workload. The muscle action potential propagation velocity
      changed in the range of about +/-2%. For the first time, a negative relationship
      between venous potassium and M-wave area was shown during voluntary exercise.
      However, there was no evidence that the decrease in muscle performance was mainly
      caused by a decrease in sarcolemmal excitability resulting from a high
      extracellular [K+].

PMID- 17434916
TI  - Signalling within the neurovascular unit in the mammalian retina.
AB  - Neuronal activity in the central nervous system evokes localized changes in blood
      flow, a response termed neurovascular coupling or functional hyperaemia. Modern
      functional imaging methods, such as functional magnetic resonance imaging (fMRI),
      measure signals related to functional hyperaemia in order to determine
      localization of brain function and to diagnose disease. The cellular mechanisms
      that underlie functional hyperaemia, however, are not well understood. Glial
      cells have been hypothesized to be intermediaries between neurons and blood
      vessels in the control of neurovascular coupling, owing to their ability to
      release vasoactive factors in response to neuronal activity. Using an in vitro
      preparation of the isolated, intact rodent retina, we have investigated two
      likely mechanisms of glial control of the vasculature: glial K(+) siphoning and
      glial induction of vasoactive arachidonic acid metabolites. Potassium siphoning
      is a process by which a K(+) current flowing through glial cells transfers K(+)
      released from active neurons to blood vessels. Since slight increases in
      extracellular K(+) can cause vasodilatation, this mechanism was hypothesized to
      contribute to neurovascular coupling. Our data, however, suggest that glial K(+)
      siphoning does not contribute significantly to neurovascular coupling in the
      retina. Instead, we suggest that glial cells mediate neurovascular coupling by
      inducing the production of two types of arachidonic acid metabolites,
      epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE),
      which dilate and constrict vessels, respectively. We show that both light flashes
      and direct glial stimulation produce vasodilatation or vasoconstriction mediated
      by EETs and 20-HETE, respectively. Further, we show that the type of vasomotor
      response observed (dilatation or constriction) depends on retinal levels of
      nitric oxide. Our data also demonstrate that glial cells are necessary
      intermediaries for signalling from neurons to blood vessels, since functional
      hyperaemia does not occur when neuron-to-glia communication is interrupted. These
      results indicate that glial cells play an important role in mediating functional
      hyperaemia and suggest that the regulation of blood flow may involve both
      vasodilating and vasoconstricting components.

PMID- 17434917
TI  - Cortical mechanisms for shifting and holding visuospatial attention.
AB  - Access to visual awareness is often determined by covert, voluntary deployments
      of visual attention. Voluntary orienting without eye movements requires
      decoupling attention from the locus of fixation, a shift to the desired location,
      and maintenance of attention at that location. We used event-related functional
      magnetic resonance imaging to dissociate these components while observers shifted
      attention among 3 streams of letters and digits, one located at fixation and 2 in
      the periphery. Compared with holding attention at the current location, shifting
      attention between the peripheral locations was associated with transient
      increases in neural activity in the superior parietal lobule (SPL) and frontal
      eye fields (FEF), as in previous studies. The supplementary eye fields and
      separate portions of SPL and FEF were more active for decoupling attention from
      fixation than for shifting attention to a new location. Large segments of
      precentral sulcus (PreCS) and posterior parietal cortex (PPC) were more active
      when attention was maintained in the periphery than when it was maintained at
      fixation. We conclude that distinct subcomponents of the dorsal frontoparietal
      network initiate redeployments of covert attention to new locations and disengage
      attention from fixation, while sustained activity in lateral regions of PPC and
      PreCS represents sustained states of peripheral attention.

PMID- 17434918
TI  - Dynamic changes in representations of preceding and upcoming reward in monkey
      orbitofrontal cortex.
AB  - We investigated how orbitofrontal cortex (OFC) contributes to adaptability in the
      face of changing reward contingencies by examining how reward representations in
      monkey orbitofrontal neurons change during a visually cued, multi-trial reward
      schedule task. A large proportion of orbitofrontal neurons were sensitive to
      events in this task (69/80 neurons in the valid and 48/58 neurons in the random
      cue context). Neuronal activity depended upon preceding reward, upcoming reward,
      reward delivery, and schedule state. Preceding reward-dependent activity occurred
      in both the valid and random cue contexts, whereas upcoming reward-dependent
      activity was observed only in the valid context. A greater proportion of neurons
      encoded preceding reward in the random than the valid cue context. The proportion
      of neurons with preceding reward-dependent activity declined as each trial
      progressed, whereas the proportion encoding upcoming reward increased. Reward
      information was represented by ensembles of neurons, the composition of which
      changed with task context and time. Overall, neuronal activity in OFC adapted to
      reflect the importance of different types of reward information in different
      contexts and time periods. This contextual and temporal adaptability is one
      hallmark of neurons participating in executive functions.

PMID- 17434919
TI  - Catecholamine and second messenger influences on prefrontal cortical networks of
      "representational knowledge": a rational bridge between genetics and the symptoms
      of mental illness.
AB  - Both dopamine (DA) and norepinephrine (NE) have powerful, inverted U influences
      on prefrontal cortical (PFC) cognitive function. Optimal NE levels engage alpha2A
      adrenoceptors and increase "signals" via inhibition of cAMP-HCN (cAMP
      hyperpolarization-activated cyclic nucleotide-gated cation channel) signaling
      near preferred inputs, whereas optimal levels of DA D1 receptor stimulation
      decrease "noise" by increasing cAMP signaling near nonpreferred inputs. Excessive
      levels of catecholamine release during stress impair working memory 1) by very
      high levels of cAMP-HCN signaling diminishing preferred as well as nonpreferred
      inputs and 2) by high levels of NE engaging alpha1 stimulation of phosphotidyl
      inositol (PI) signaling that suppresses cell firing. Common mental illnesses are
      associated with extracellular changes in these pathways: Attention Deficit
      Hyperactivity Disorder is linked to genetic changes that reduce catecholamine
      transmission to suboptimal levels and is treated with agents that increase
      catecholamine transmission, whereas Post-Traumatic Stress Disorder (PTSD) is
      associated with amplified noradrenergic transmission that impairs PFC but
      strengthens amygdala function. PTSD is now treated with agents that block alpha1
      or beta adrenoceptors. In contrast, the more severe mental illnesses,
      schizophrenia and bipolar disorder, are associated with genetic changes in
      molecules regulating intracellular signaling pathways activated by stress.
      Specifically, DISC1 inhibits cAMP signaling whereas regulator of G-protein
      signaling 4 inhibits PI signaling. Loss of function in these genes may render
      patients vulnerable to profound stress-induced PFC dysfunction including symptoms
      of thought disorder.

PMID- 17434920
TI  - Contribution of the orphan nuclear receptor Nur77 to the apoptotic action of
      IGFBP-3.
AB  - Tumor suppression by insulin-like growth factor-binding protein-3 (IGFBP-3) has
      been demonstrated to occur via insulin-like growth factor-dependent and 
      independent mechanisms in vitro and in vivo. We have recently described IGFBP-3
      induced mitochondrial translocation of the nuclear receptors RXRalpha/Nur77 in
      the induction of prostate cancer (CaP) cell apoptosis. Herein, we demonstrate
      that IGFBP-3 and Nur77 associate in the cytoplasmic compartment in 22RV1 CaP
      cells. Nur77 is a major component of IGFBP-3-induced apoptosis as shown by
      utilizing mouse embryonic fibroblasts (MEFs) derived from Nur77 wild-type and
      knockout (KO) mice. However, dose-response experiments revealed that a small
      component of IGFBP-3-induced apoptosis is Nur77 independent. Reintroduction of
      Nur77 into Nur77 KO MEFs restores full responsiveness to IGFBP-3. IGFBP-3 induces
      phosphorylation of Jun N-terminal kinase and inhibition of Akt phosphorylation
      and activity, which have been associated with Nur77 translocation. Finally, IGFBP
      3 administration to CaP xenografts on SCID mice induced apoptosis and
      translocated Nur77 out of the nucleus. Taken together, our results verify an
      important role for the orphan nuclear receptor Nur77 in the apoptotic actions of
      IGFBP-3.

PMID- 17434921
TI  - Association between CYP3A4 genotype and risk of endometrial cancer following
      tamoxifen use.
AB  - Tamoxifen is a selective estrogen receptor modulator that is used to treat and to
      prevent breast cancer; however, its use is associated with an increased risk of
      endometrial cancer. Tamoxifen is metabolized by various cytochrome P450 (CYP)
      enzymes, but predominantly by CYP3A4. In this study, we examined whether a
      genetic variant of the CYP3A4 gene, CYP3A4*1B, influences endometrial cancer risk
      -alone and when associated with tamoxifen exposure. We conducted a case-control
      study on 566 endometrial cancer cases and 964 ethnically matched controls. The
      variant CYP3A4 allele was present in 6% of the controls and 9% of the endometrial
      cancer patients (OR = 1.6, 95% CI = 1.1-2.3, P = 0.02). The allele was more
      common in women with endometrial cancer who had been treated with tamoxifen for
      breast cancer (16%). Women who carried the CYP3A4*1B allele had approximately 3
      fold increase in the risk of developing endometrial cancer following tamoxifen
      treatment, compared with women who did not take tamoxifen (P = 0.004). These
      findings suggest that a subgroup of breast cancer patients who carry the
      CYP3A4*1B allele and take tamoxifen may be at increased risk of developing
      endometrial cancer.

PMID- 17434922
TI  - Cancer genomics: integrating form and function.
AB  - The sequencing of the human genome has formed the foundation with which to
      develop technologies and reagents to perform true genome-scale biological
      studies. In particular, the development and increasing application of these high
      throughput genome-scale technologies have fundamentally altered the way one can
      approach the analysis of cancer. It is now possible to imagine studies that
      interrogate the structure, expression and function of every gene in a
      comprehensive, highly parallel fashion, permitting the development of
      multidimensional, global views of cancer. In this review, we focus on recent
      advances in the application of genomic strategies to the study of cancer, with an
      emphasis on functional genomics and the prospects for integrating the knowledge
      gained from these approaches to further develop our understanding of cancer and
      design better therapeutic strategies.

PMID- 17434923
TI  - Functional characterization of single-nucleotide polymorphisms and haplotypes of
      human N-acetyltransferase 2.
AB  - Human N-acetyltransferase 2 (NAT2) is polymorphic in humans and may associate
      with cancer risk by modifying individual susceptibility to cancers from
      carcinogen exposure. Since molecular epidemiological studies investigating these
      associations usually include determining NAT2 single-nucleotide polymorphisms
      (SNPs), haplotypes or genotypes, their conclusions can be compromised by the
      uncertainty of genotype-phenotype relationships. We characterized NAT2 SNPs and
      haplotypes by cloning and expressing recombinant NAT2 allozymes in mammalian
      cells. The reference and variant recombinant NAT2 allozymes were characterized
      for arylamine N-acetylation and O-acetylation of N-hydroxy-arylamines. SNPs and
      haplotypes that conferred reduced enzymatic activity did so by reducing NAT2
      protein without changing NAT2 mRNA levels. Among SNPs that reduced catalytic
      activity, G191A (R64Q), G590A (R197Q) and G857A (G286E) reduced protein half-life
      but T341C (I114T), G499A (E167K) and A411T (L137F) did not. G857A (G286E) and the
      major haplotype possessing this SNP (NAT2 7B) altered the affinity to both
      substrate and cofactor acetyl coenzyme A, resulting in reduced catalytic activity
      toward some substrates but not others. Our results suggest that coding region
      SNPs confer slow acetylator phenotype by multiple mechanisms that also may vary
      with arylamine exposures.

PMID- 17434924
TI  - MC1R: three novel variants identified in a malignant melanoma association study
      in the Spanish population.
AB  - The human melanocortin-1 receptor (MC1R) gene, which plays a crucial role in
      pigmentation, also appears to be important in malignant melanoma (MM). This case
      control study in the Spanish population included 116 consecutive MM patients and
      188 controls frequency matched for sex and age. Sequence analysis of the entire
      coding region of MC1R was performed, identifying 21 variants, all of them
      previously reported except for three novel non-synonymous changes: Ser41Phe,
      Met128Thr and Asn281Ser. Simulated structural analyses suggested disruption of
      the local structure around Phenylalanine 41, possible destabilization of the
      hydrophobic interior of the molecule in Threonine 128 and that Asparagine 281
      could be in a region of functional importance. The fact that these three novel
      variants were not present in 1,000 healthy individuals tested adds further weight
      to them having putative adverse effects on the functional protein. Six variants,
      all non-synonymous changes, were individually associated with MM risk (Arg160Trp,
      Asp294His, Val60Leu, Val92Met, Ile155Thr and Arg163Gln). Carrying two non
      synonymous variants was associated with much higher risk of MM (odds ratio:
      10.44, 95% confidence interval = 4.48-24.33, P = 5 x 10(-8)) and haplotype
      analysis, verified by cloning, confirmed that this is predominantly due to
      carrying each on a different chromosome. Our results suggest that both red hair
      colour (RHC) and non-red hair colour variants, and possibly other rare non
      synonymous variants, in MC1R are implicated in the development of MM. In addition
      to carrying MC1R variant alleles, having blond/red hair and childhood sunburns
      were independent risk factors for MM.

PMID- 17434925
TI  - Aristolochic acid mutagenesis: molecular clues to the aetiology of Balkan endemic
      nephropathy-associated urothelial cancer.
AB  - Balkan endemic nephropathy (BEN) is found in certain rural areas of the Balkans
      and affects at least 25,000 inhabitants. Of the many hypotheses on BEN, the
      Aristolochia hypothesis has recently gained ground substantiated by the
      investigations on aristolochic acid nephropathy (AAN). On both clinical and
      morphological grounds, AAN is very similar to BEN. That exposure to aristolochic
      acid (AA) of individuals living in endemic areas through consumption of bread
      made with flour contaminated with seeds of Aristolochia clematitis is responsible
      for BEN is an old hypothesis, but one which is fully consistent with the unique
      epidemiologic features of BEN. Here, we propose an approach to investigate AA
      induced mutagenesis in BEN that can provide molecular clues to the aetiology of
      its associated urothelial cancer. The molecular mechanism of AA-induced
      carcinogenesis demonstrates a strong association between DNA adduct formation,
      mutation pattern and tumour development. A clear link between urothelial tumours,
      p53 mutations and AA exposure should emerge as more tumour DNA from BEN patients
      from different endemic areas becomes available for mutation analysis. We predict
      that the observed p53 mutation spectrum will be dominated by AT --> TA
      transversion mutations as has already been demonstrated in the human p53 gene of
      immortalized cells after exposure to AAI and urothelial tumours from BEN patients
      in Croatia. Moreover, the detection of AA-specific DNA adducts in renal tissue of
      a number of BEN patients and individuals living in areas endemic for BEN in
      Croatia provides new evidence that chronic exposure to AA is a risk factor for
      BEN and its associated cancer.

PMID- 17434926
TI  - Chemopreventive effects of lupulone, a hop {beta}-acid, on human colon cancer
      derived metastatic SW620 cells and in a rat model of colon carcinogenesis.
AB  - The bitter acids of hops (Humulus lupulus L.) mainly consist of humulones or
      alpha-acids and lupulones or beta-acids. We aimed to evaluate the
      antiproliferative mechanisms of lupulones on a human metastatic colon carcinoma
      derived cell line (SW620 cells) and to assess their chemopreventive effects in a
      model of colon carcinogenesis. SW620 cell growth was inhibited by 70% after a 48
      h exposure to lupulones (40 microg/ml). Lupulones up-regulated the expression of
      Fas receptor (Fas) and Fas ligand (FasL) as well as TNF-related apoptosis
      inducing ligand (TRAIL)-R1 (DR4) and -R2 (DR5) receptor proteins, suggesting the
      involvement of Fas and TRAIL receptors-mediated pathways in lupulone-induced
      apoptosis. Lupulones also increased the mitochondrial membrane permeability.
      Colon carcinogenesis was initiated in Wistar rats by intra-peritoneal injections
      of azoxymethane (AOM), once a week for 2 weeks. One week after the last
      injection, rats received lupulones (0.001 or 0.005%) in drinking water, and AOM
      control rats received the excipient. After 7 months of treatment, the colon of
      rats receiving 0.001 and 0.005% lupulones showed, respectively, a 30 and a 50%
      reduction (P < 0.05) of the number of preneoplastic lesions (aberrant crypt
      foci). In addition, we observed a drastic reduction (70-80%) of the total number
      of tumors in the colon of rats treated with lupulones when compared with the AOM
      control group. Lupulones induced apoptosis in SW620 colon-derived metastatic
      cells by activating both Fas and TRAIL death receptor signaling pathways, and
      antagonize at a low dose (4 mg/kg/day) colon cancer development. These
      observations suggest the use of lupulones for colon cancer chemoprevention
      trials.

PMID- 17434927
TI  - Loss of p27Kip1 enhances tumor progression in chronic hepatocyte injury-induced
      liver tumorigenesis with widely ranging effects on Cdk2 or Cdc2 activation.
AB  - Effects of p27Kip1 inactivation on tumorigenesis vary from promotion to
      prevention dependent on the mouse models used. When p27 inactivation has a
      positive effect on tumorigenesis, de-regulated activation of cyclin-dependent
      kinases (Cdks) is generally believed to be the underlying mechanism since the
      function of p27 as an inhibitor of Cdks is firmly established. Here, we
      determined the effects of p27 inactivation on disease progression and Cdk
      activation in mouse liver tumorigenesis that originates from hepatocyte
      regenerative proliferation in response to chronic liver injury, an established
      etiology in most human liver cancer. Our results show that inactivation of p27
      did not affect early-stage hepatocyte regenerative proliferation but promoted
      tumor cell proliferation and progression in the late stage of the disease.
      Interestingly, Cdc2 over-expression was observed in all and cyclin E1 was over
      expressed in half of the late-stage tumors regardless of p27 status; and p27
      inactivation led to significant activation of Cdk2 or Cdc2 only in half of the
      p27-deficient tumors. These results reveal a tumor suppressor role of p27 in
      chronic hepatocyte injury-induced liver tumorigenesis and, at the same time, the
      need to further study the mechanisms for tumor promotion by p27 inactivation.

PMID- 17434928
TI  - Bcl-2 over-expression promotes genomic instability by inhibiting apoptosis of
      cells exposed to hydrogen peroxide.
AB  - The anti-apoptotic oncogene bcl-2 is hypothesized to increase the antioxidant
      status of cells, thereby protecting them from oxidative stress. In this study, we
      examined hydrogen peroxide (H2O2)-mediated oxidative stress in Jurkat T lymphoma
      cells. Over-expression of Bcl-2 did not inhibit cytotoxicity at doses of H2O2
      that caused necrosis (>200 microM), but it did block cell death at apoptotic
      doses (<200 microM). However, these cells exhibited the same initial level of
      protein and lipid oxidation following exposure to H2O2 as the parental cells,
      indicating that the anti-apoptotic activity is not associated with general
      antioxidant properties. Bcl-2 expression was able to protect against secondary
      protein carbonyl formation, which was linked to lysosome stabilization.
      Assessment of micronuclei formation in cells over-expressing Bcl-2 showed
      evidence of increased genomic instability, consistent with the impairment of
      apoptosis in damaged cells. We conclude that while Bcl-2 can block cytotoxicity
      associated with apoptosis-inducing levels of oxidative stress, it does not
      protect the cells from the stress itself. Bcl-2 may promote tumourigenesis by
      preventing the removal of oxidatively damaged cells.

PMID- 17434929
TI  - The CBF1-independent Notch1 signal pathway activates human c-myc expression
      partially via transcription factor YY1.
AB  - Transcription factor Ying Yang 1 (YY1) indirectly regulates the C promoter
      binding factor 1 (CBF1)-dependent Notch1 signaling via direct interaction with
      the Notch1 receptor intracellular domain (N1IC) on CBF1-response elements. To
      evaluate the possibility that the N1IC might modulate the gene expression of YY1
      target genes through associating with YY1 on the YY1-response elements, we herein
      investigated the effect of Notch1 signaling on the expression of YY1 target
      genes. We found that the N1IC bound to the double-stranded oligonucleotides of
      YY1-response element to activate luciferase activity of the reporter gene with
      YY1-response elements through a CBF1-independent manner. Furthermore, the N1IC
      also bound to the promoter of human c-myc oncogene, a YY1 target gene, to elevate
      c-myc expression via a CBF1-independent pathway. The activation of reporter genes
      with YY1-response elements or human c-myc promoter by N1IC depended on the
      formation of N1IC-YY1-associated complex. To delineate the role of the Notch
      signal pathway in tumorigenesis, K562 cell lines expressing the N1IC were
      established. Compared with control cells, the proliferation and the tumor growth
      of N1IC-expressing K562 cells were suppressed. Taken together, these results
      suggest that the N1IC enhances the human c-myc promoter activity that is
      partially modulated by YY1 through a CBF1-independent pathway. However, the
      enhancement of c-myc expression by N1IC is insufficient to promote the tumor
      growth of K562 cells.

PMID- 17434930
TI  - The use of a cyclooxygenase-2 inhibitor (Nepafenac) in an ocular and metastatic
      animal model of uveal melanoma.
AB  - The expression of cyclooxygenase-2 (COX-2) has been reported as an indicator of
      poor prognosis in a wide variety of human tumors, including colon, breast and
      uveal melanoma (UM). COX-2 inhibitors have shown promise in controlling the
      malignancy of several types of tumors. Previous studies have demonstrated the
      efficacy of a COX-2 inhibitor on the proliferation rates of human UM cells. The
      goal of this experiment was to investigate the efficiency of Nepafenac, a
      topically administered COX-2 inhibitor, in a rabbit model of UM. The animals were
      divided into two groups of 14 animals for the duration of the 12-week experiment.
      One animal per group was killed each week to evaluate disease progression and for
      histopathological studies. The experimental group received drops containing 0.3%
      Nepafenac solution. Intraocular tumor growth was evaluated weekly by fundoscopic
      examination and each animal was weighed prior to examination. Blood samples were
      taken weekly from all rabbits to detect circulating malignant cells (CMCs)
      throughout the experiment. After the second week of inoculation, the experimental
      group weighed significantly more than the control group. The control group
      developed more intraocular tumors and presented with metastases and higher
      detectable levels of CMCs before the treated group. These results indicate that
      the topical administration of a COX-2 inhibitor delayed the progression of this
      malignancy in our animal model. A clinical trail using an anti-COX-2 inhibitor
      for patients with UM should be considered.

PMID- 17434931
TI  - Potential role of ferritin heavy chain in oxidative stress and apoptosis in human
      mesothelial and mesothelioma cells: implications for asbestos-induced
      oncogenesis.
AB  - Exposure to asbestos is a known etiological factor in malignant mesothelioma
      (MM). However, in vitro cell culture studies have provided paradoxical evidence
      that asbestos exposure to mesothelial cells causes cytotoxicity or apoptosis
      rather than malignant transformation. Although it has been shown that the iron
      associated with asbestos participates in the cell toxicity and probably MM
      pathogenesis via generation of reactive oxygen species (ROS), the molecular
      mechanisms largely remain unknown. Here, we demonstrate that ferritin heavy chain
      (FHC), a core subunit of iron-binding protein ferritin, works as an anti
      apoptotic protein against toxic asbestos and oxidative stress in human
      mesothelial cells and MM cells. We found that FHC was induced in asbestos-exposed
      MeT-5A human mesothelial cells. The mesothelial cell line stably expressing FHC
      generated less amount of hydrogen peroxide (H2O2), one of the main ROS, after
      asbestos exposure and was more resistant to apoptosis induced by H2O2 compared
      with the cells transfected with the empty vector. Next, we investigated
      biological roles of FHC in human MM cell. We found that NCI-H2052, a human MM
      cell line, had a higher expression of endogenous FHC than MeT-5A and used the
      cell to address FHC function in MM. NCI-H2052 showed reduced H2O2 production and
      an apoptosis-resistant phenotype compared with MeT-5A. Suppression of the over
      expressed FHC by using FHC small interfering RNA rendered the MM cells sensitive
      to apoptosis, suggesting the contribution of FHC to apoptosis resistance of the
      MM cells. Our findings highlight the potential role of FHC in the pathogenesis of
      asbestos-induced mesothelioma.

PMID- 17434933
TI  - DNA compaction by the nuclear factor-Y.
AB  - The nuclear factor-Y (NF-Y), a trimeric, CCAAT-binding transcriptional activator
      with histone-like subunits, was until recently considered a prototypical promoter
      transcription factor. However, recent in vivo chromatin immunoprecipitation
      assays associated with microarray methodologies (chromatin immunoprecipitation on
      chip experiments) have indicated that a large portion of target sites (40%-50%)
      are located outside of core promoters. We applied the tethered particle motion
      technique to the major histocompatibility complex class II enhancer-promoter
      region to characterize i), the progressive compaction of DNA due to increasing
      concentrations of NF-Y, ii), the role of specific subunits and domains of NF-Y in
      the process, and iii), the interplay between NF-Y and the regulatory factor-X,
      which cooperatively binds to the X-box adjacent to the CCAAT box. Our study shows
      that NF-Y has histone-like activity, since it binds DNA nonspecifically with high
      affinity to compact it. This activity, which depends on the presence of all
      trimer subunits and of their glutamine-rich domains, seems to be attenuated by
      the transcriptional cofactor regulatory factor-X. Most importantly NF-Y-induced
      DNA compaction may facilitate promoter-enhancer interactions, which are known to
      be critical for expression regulation.

PMID- 17434932
TI  - Toxoplasma gondii and schizophrenia: linkage through astrocyte-derived kynurenic
      acid?

PMID- 17434934
TI  - Conduction properties of KcsA measured using brownian dynamics with flexible
      carbonyl groups in the selectivity filter.
AB  - In the narrow segment of an ion conducting pathway, it is likely that a
      permeating ion influences the positions of the nearby atoms that carry partial or
      full electronic charges. Here we introduce a method of incorporating the motion
      of charged atoms lining the pore into Brownian dynamics simulations of ion
      conduction. The movements of the carbonyl groups in the selectivity filter of the
      KcsA channel are calculated explicitly, allowing their bond lengths, bond angles,
      and dihedral angels to change in response to the forces acting upon them. By
      systematically changing the coefficients of bond stretching and of angle bending,
      the carbon and oxygen atoms can be made to fluctuate from their fixed positions
      by varying mean distances. We show that incorporating carbonyl motion in this way
      does not alter the mechanism of ion conduction and only has a small influence on
      the computed current. The slope conductance of the channel increases by
      approximately 25% when the root mean-square fluctuations of the carbonyl groups
      are increased from 0.01 to 0.61 A. The energy profiles and the number of resident
      ions in the channel remain unchanged. The method we utilized here can be extended
      to allow the movement of glutamate or aspartate side chains lining the
      selectivity filters of other ionic channels.

PMID- 17434935
TI  - Analysis of kinetics in noisy systems: application to single molecule tethered
      particle motion.
AB  - In the tethered particle motion method the length of a DNA molecule is monitored
      by measuring the range of diffusion of a microsphere tethered to the surface of a
      microscope coverslip through the DNA molecule itself. Looping of DNA (induced by
      binding of a specific protein) can be detected with this method and the kinetics
      of the looping/unlooping processes can be measured at the single molecule level.
      The microsphere's position variance represents the experimental variable
      reporting on the polymer length. Therefore, data windowing is required to obtain
      position variance from raw position data. Due to the characteristic diffusion
      time of the microsphere, the low-pass filtering required to attain a good
      signal/noise ratio (S/N) in the discrimination of looped versus unlooped state
      impacts significantly the measurement's time resolution. Here we present a method
      for measuring lifetimes based on half-amplitude thresholding and then correcting
      the kinetic measurements, taking into account low S/N (leading to false events)
      and limited time resolution (leading to missed events). This method allows an
      accurate and unbiased estimation of the kinetic parameters under investigation,
      independently of the choice of the window used for variance calculation, with
      potential applications to other single molecule measurements with low S/N.

PMID- 17434936
TI  - A novel cell force sensor for quantification of traction during cell spreading
      and contact guidance.
AB  - In this work, we present a ridged, microfabricated, force sensor that can be used
      to investigate mechanical interactions between cells exhibiting contact guidance
      and the underlying cell culture substrate, and a proof-of-function evaluation of
      the force sensor performance. The substrates contain arrays of vertical pillars
      between solid ridges that were microfabricated in silicon wafers using
      photolithography and deep reactive ion etching. The spring constant of the
      pillars was measured by atomic force microscopy. For time-lapse experiments,
      cells were seeded on the pillared substrates and cultured in an on-stage
      incubator on a microscope equipped with reflected differential interference
      contrast optics. Endothelial cells (ECs) and fibroblasts were observed during
      attachment, spreading, and migration. Custom image analysis software was
      developed to resolve cell borders, cell alignment to the pillars and migration,
      displacements of individual pillars, and to quantify cell traction forces.
      Contact guidance classification was based on cell alignment and movement angles
      with respect to microfabricated ridges, as well as cell elongation. In initial
      investigations made with the ridged cell force sensor, we have observed contact
      guidance in ECs but not in fibroblast cells. A difference in maximal amplitude of
      mechanical forces was observed between a contact-guided and non-contact-guided,
      but mobile, EC. However, further experiments are required to determine the
      statistical significance of this observation. By chance, we observed another
      feature of cell behavior, namely a reversion of cell force direction. The
      direction of forces measured under rounded fibroblast cells changed from outwards
      during early cell attachment to inwards during further observation of the
      spreading phase. The range of forces measured under fibroblasts (up to 138 nN)
      was greater than that measured in EC (up to 57 nN), showing that the rigid
      silicon sensor is capable of resolving a large range of forces, and hence
      detection of differences in traction forces between cell types. These
      observations indicate proof-of-function of the ridged cell force sensor to induce
      contact guidance, and that the pillared cell force sensor constructed in rigid
      silicon has the necessary sensitivity to detect differences in traction force
      vectors between different cell phenotypes and morphologies.

PMID- 17434937
TI  - A programmable optical angle clamp for rotary molecular motors.
AB  - Optical tweezers are widely used for experimental investigation of linear
      molecular motors. The rates and force dependence of steps in the mechanochemical
      cycle of linear motors have been probed giving detailed insight into motor
      mechanisms. With similar goals in mind for rotary molecular motors we present
      here an optical trapping system designed as an angle clamp to study the bacterial
      flagellar motor and F(1)-ATPase. The trap position was controlled by a digital
      signal processing board and a host computer via acousto-optic deflectors, the
      motor position via a three-dimensional piezoelectric stage and the motor angle
      using a pair of polystyrene beads as a handle for the optical trap. Bead-pair
      angles were detected using back focal plane interferometry with a resolution of
      up to 1 degrees , and controlled using a feedback algorithm with a precision of
      up to 2 degrees and a bandwidth of up to 1.6 kHz. Details of the optical trap,
      algorithm, and alignment procedures are given. Preliminary data showing angular
      control of F(1)-ATPase and angular and speed control of the bacterial flagellar
      motor are presented.

PMID- 17434938
TI  - Simulating the temporal modulation of inducible DNA damage response in
      Escherichia coli.
AB  - Living organisms make great efforts to maintain their genetic information
      integrity. However, DNA is vulnerable to many chemical or physical agents. To
      rescue the cell timely and effectively, the DNA damage response system must be
      well controlled. Recently, single cell experiments showing that after DNA damage,
      expression of the key DNA damage response regulatory protein oscillates with
      time. This phenomenon is observed both in eukaryotic and bacterial cells. We
      establish a model to simulate the DNA damage response (SOS response) in bacterial
      cell Escherichia coli. The simulation results are compared to the experimental
      data. Our simulation results suggest that the modulation observed in the
      experiment is due to the fluctuation of inducing signal, which is coupled with
      DNA replication. The inducing signal increases when replication is blocked by DNA
      damage and decreases when replication resumes.

PMID- 17434939
TI  - Binding of lysozyme to phospholipid bilayers: evidence for protein aggregation
      upon membrane association.
AB  - Biological functions of lysozyme, including its antimicrobial, antitumor, and
      immune-modulatory activities have been suggested to be largely determined by the
      lipid binding properties of this protein. To gain further insight into these
      interactions on a molecular level the association of lysozyme to liposomes
      composed of either 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine or its
      mixtures with 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol, 1-palmitoyl
      2-oleoyl-sn-glycero-3-phospho-rac-phosphatidylserine, or bovine heart cardiolipin
      was studied by a combination of fluorescence techniques. The characteristics of
      the adsorption of lysozyme to lipid bilayers were investigated using fluorescein
      5'-isothiocyanate labeled protein, responding to membrane association by a
      decrease in fluorescence. Upon increasing the content of anionic phospholipids in
      lipid vesicles, the binding isotherms changed from Langmuir-like to sigmoidal.
      Using adsorption models based on scaled particle and double-layer theories, this
      finding was rationalized in terms of self-association of the membrane-bound
      protein. The extent of quenching of lysozyme tryptophan fluorescence by
      acrylamide decreased upon membrane binding, revealing a conformational transition
      for the protein upon its surface association, resulting in a diminished access of
      the fluorophore to the aqueous phase. Steady-state fluorescence anisotropy of
      bilayer-incorporated probe 1,6-diphenyl-1,3,5-hexatriene was measured at varying
      lipid-to-protein molar ratios. Lysozyme was found to increase acyl-chain order
      for liposomes with the content of acidic phospholipid exceeding 10 mol %. Both
      electrostatic and hydrophobic protein-lipid interactions can be concluded to
      modulate the aggregation behavior of lysozyme when bound to lipid bilayers.
      Modulation of lysozyme aggregation propensity by membrane binding may have
      important implications for protein fibrillogenesis in vivo. Disruption of
      membrane integrity by the aggregated protein species is likely to be the
      mechanism responsible for the cytotoxicity of lysozyme.

PMID- 17434940
TI  - Comparison of DPPC and DPPG environments in pulmonary surfactant models.
AB  - Deuterium nuclear magnetic resonance was used to monitor lipid acyl-chain
      orientational order in suspensions of dipalmitoylphosphatidylcholine (DPPC) and
      dipalmitoylphosphatidylglycerol (DPPG) containing Ca(2+) and the lung surfactant
      proteins SP-A and SP-B separately and together. To distinguish between protein
      lipid interactions involving the PC and PG lipid headgroups and to examine
      whether such interactions might influence spatial distribution of lipids within
      the bilayer, acyl chains on either the DPPC or the DPPG component of the mixture
      were deuterated. The lipid components of the resulting mixtures were thus either
      DPPC-d(62)/DPPG (7:3) or DPPC/DPPG-d(62) (7:3), respectively. SP-A had little
      effect on DPPC-d(62) chain order but did narrow the temperature range over which
      DPPG-d(62) ordered at the liquid-crystal-to-gel transition. No segregation of
      lipid components was seen for temperatures above or below the transition. Near
      the transition, though, there was evidence that SP-A promoted preferential
      depletion of DPPG from liquid crystalline domains in the temperature range over
      which gel and liquid crystal domains coexist. SP-B lowered average chain order of
      both lipids both above and below the main transition. The perturbations of chain
      order by SP-A and SP-B together were smaller than by SP-B alone. This reduction
      in perturbation of the lipids by the additional presence of SP-A likely indicated
      a strong interaction between SP-A and SP-B. The competitive lipid-lipid, lipid
      protein, and protein-protein interactions suggested by these observations
      presumably facilitate the reorganization of surfactant material inherent in the
      transformation from lamellar bodies to a functional surfactant layer.

PMID- 17434941
TI  - Entropic elasticity controls nanomechanics of single tropocollagen molecules.
AB  - We report molecular modeling of stretching single molecules of tropocollagen, the
      building block of collagen fibrils and fibers that provide mechanical support in
      connective tissues. For small deformation, we observe a dominance of entropic
      elasticity. At larger deformation, we find a transition to energetic elasticity,
      which is characterized by first stretching and breaking of hydrogen bonds,
      followed by deformation of covalent bonds in the protein backbone, eventually
      leading to molecular fracture. Our force-displacement curves at small forces show
      excellent quantitative agreement with optical tweezer experiments. Our model
      predicts a persistence length xi(p) approximately 16 nm, confirming experimental
      results suggesting that tropocollagen molecules are very flexible elastic
      entities. We demonstrate that assembly of single tropocollagen molecules into
      fibrils significantly decreases their bending flexibility, leading to decreased
      contributions of entropic effects during deformation. The molecular simulation
      results are used to develop a simple continuum model capable of describing an
      entire deformation range of tropocollagen molecules. Our molecular model is
      capable of describing different regimes of elastic and permanent deformation,
      without relying on empirical parameters, including a transition from entropic to
      energetic elasticity.

PMID- 17434942
TI  - Spectroscopic and structural study of proton and halide ion cooperative binding
      to gfp.
AB  - This study reports the influence of halogens on fluorescence properties of the
      Aequorea victoria Green Fluorescent Protein variant S65T/T203Y (E(2)GFP). Halide
      binding forms a specific nonfluorescent complex generating a substantial drop of
      the fluorescence via static quenching. Spectroscopic analysis under different
      solution conditions reveals high halogen affinity, which is strongly dependent on
      the pH. This evidences the presence in E(2)GFP of interacting binding sites for
      halide ions and for protons. Thermodynamic link and cooperative interaction are
      assessed demonstrating that binding of one halide ion is associated with the
      binding of one proton in a cooperative fashion with the formation, in the pH
      range 4.5-10, of a single fully protonated E(2)GFP.halogen complex. To resolve
      the structural determinants of E(2)GFP sensitivity to halogens, high-resolution
      crystallographic structures were obtained for the halide-free and I(-), Br(-),
      and Cl(-) bound E(2)GFP. Remarkably the first high-resolution (1.4 A)
      crystallographic structure of a chloride-bound GFP is reported. The chloride ion
      occupies a specific and unique binding pocket in direct contact (3.4 A) with the
      chromophore imidazolidinone aromatic ring. Unanticipated flexibility, strongly
      modulated by halide ion interactions, is observed in the region surrounding the
      chromophore. Furthermore molecular dynamics simulations identified E222 residue
      (along with the chromophore Y66 residue) being in the protonated state when
      E(2)GFP.halogen complex is formed. The impact of these results on high
      sensitivity biosensor design will be discussed.

PMID- 17434943
TI  - Effect of the physicochemical properties of poly(ethylene glycol) brushes on
      their binding to cells.
AB  - We investigated the effect of the number of oxyethylene groups (polymer molecular
      weight) and the interchain binding and/or entanglements of methoxy-terminated
      poly(ethylene glycol) (m-PEG) brushes on their ability to adsorb to living
      malignant melanoma B16F10 cells. We used the atomic force microscope colloid
      probe method to determine the adhering ability of the m-PEG brushes to the cells,
      as the magnitude of the adhesion force between the m-PEG modified particles and
      the living cells in a physiological buffer was related to the binding strength of
      the m-PEGs to the cells. We saw that m-PEG brushes (average molecular weights
      330, 1900, and 5000 g/mol), which were chemically attached to silica particles,
      may bind to living B16F10 cells. The binding of m-PEGs to living B16F10 cells
      increased as the oxyethylene chain length of the m-PEGs increased, if the m-PEGs
      had a low degree of entanglements or little inter-m-PEG chain binding. A high
      degree of entanglements or interchain binding decreased the ability of an m-PEG
      chain to bind to a living cell. The effect of m-PEG (molecular weight 1900 g/mol)
      being present at cell surfaces for 24 h was also seen not to induce the death of
      the cells or affect their growth.

PMID- 17434944
TI  - The chemical and dynamical influence of the anti-viral drug amantadine on the M2
      proton channel transmembrane domain.
AB  - The M(2) proton channel plays a vital role in the life cycle of the influenza A
      virus. His(37), the key residue in the M(2) transmembrane domain (M(2)-TMD),
      plays a central role in the proton conductance mechanism. The anti-influenza
      drug, amantadine, inhibits the channel activity through binding to the pore of
      the M(2) channel. The nuclear spin relaxation data and polarization inversion
      spin exchange at the magic angle spectra show that both the polypeptide backbone
      and His(37) side chain are more constrained in the presence of amantadine. Using
      (15)N cross polarization magic-angle spinning NMR spectroscopy, the protonation
      of His(37) of M(2)-TMD in lipid bilayers was monitored in the absence and
      presence of amantadine as a function of pH. Binding amantadine lowers the His(37)
      pK(a) values by approximately three orders of magnitude compared with the first
      pK(a) of histidine in amantadine-free M(2)-TMD. Amantadine's influence on the
      His(37) chemical properties suggests a novel mechanism by which amantadine may
      inhibit proton conductance.

PMID- 17434945
TI  - On the equivalence point for ammonium (de)protonation during its transport
      through the AmtB channel.
AB  - Structural characterization of the bacterial channel, AmtB, provides a glimpse of
      how members of its family might control the protonated state of permeant ammonium
      to allow for its selective passage across the membrane. In a recent study, we
      employed a combination of simulation techniques that suggested ammonium is
      deprotonated and reprotonated near dehydrative phenylalanine landmarks (F107 and
      F31, respectively) during its passage from the periplasm to the cytoplasm. At
      these landmarks, ammonium is forced to maintain a critical number ( approximately
      3) of hydrogen bonds, suggesting that the channel controls ammonium
      (de)protonation by controlling its coordination/hydration. In the work presented
      here, a free energy-based analysis of ammonium hydration in dilute aqueous
      solution indicates, explicitly, that at biological pH, the transition from
      ammonium (NH(4)(+)) to ammonia (NH(3)) occurs when these species are constrained
      to donate three hydrogen bonds or less. This result demonstrates the viability of
      the proposal that AmtB indirectly controls ammonium (de)protonation by directly
      controlling its hydration.

PMID- 17434946
TI  - The lipid dependence of melittin action investigated by dual-color fluorescence
      burst analysis.
AB  - Dual-color fluorescence-burst analysis was used to study melittin-induced leakage
      of macromolecules from liposomes of various lipid compositions. To perform dual
      color fluorescence-burst analysis, fluorescently labeled size-marker molecules
      were encapsulated into liposomes, labeled with a second lipid-attached
      fluorophore. By correlating the fluorescence bursts, resulting from the liposomes
      diffusing through the detection volume of a dual-color confocal microscope, the
      distribution of size-marker molecules over the liposomes was determined. It was
      found that melittin causes leakage via two different mechanisms: 1), For
      liposomes composed of neutral bilayer-forming lipids, low melittin concentrations
      induced pore formation with the pore size depending on the melittin
      concentration. 2), For liposomes containing anionic and/or nonbilayer forming
      lipids, melittin induced fusion or aggregation of liposomes accompanied by a
      specific leakage. Experiments with liposomes prepared from Escherichia coli lipid
      extracts and intact cells of Lactococcus lactis indicate that both mechanisms are
      physiologically relevant.

PMID- 17434947
TI  - Sugar transport across lactose permease probed by steered molecular dynamics.
AB  - Escherichia coli lactose permease (LacY) transports sugar across the inner
      membrane of the bacterium using the proton motive force to accumulate sugar in
      the cytosol. We have probed lactose conduction across LacY using steered
      molecular dynamics, permitting us to follow molecular and energetic details of
      lactose interaction with the lumen of LacY during its permeation. Lactose induces
      a widening of the narrowest parts of the channel during permeation, the widening
      being largest within the periplasmic half-channel. During permeation, the water
      filled lumen of LacY only partially hydrates lactose, forcing it to interact with
      channel lining residues. Lactose forms a multitude of direct sugar-channel
      hydrogen bonds, predominantly with residues of the flexible N-domain, which is
      known to contribute a major part of LacY's affinity for lactose. In the
      periplasmic half-channel lactose predominantly interacts with hydrophobic channel
      lining residues, whereas in the cytoplasmic half-channel key protein-substrate
      interactions are mediated by ionic residues. A major energy barrier against
      transport is found within a tight segment of the periplasmic half-channel where
      sugar hydration is minimal and protein-sugar interaction maximal. Upon unbinding
      from the binding pocket, lactose undergoes a rotation to permeate either half
      channel with its long axis aligned parallel to the channel axis. The results hint
      at the possibility of a transport mechanism, in which lactose permeates LacY
      through a narrow periplasmic half-channel and a wide cytoplasmic half-channel,
      the opening of which is controlled by changes in protonation states of key
      protein side groups.

PMID- 17434948
TI  - Triplet exciton formation as a novel photoprotection mechanism in chlorosomes of
      Chlorobium tepidum.
AB  - Chlorosomes comprise thousands of bacteriochlorophylls (BChl c, d, or e) in a
      closely packed structure surrounded by a lipid-protein envelope and additionally
      contain considerable amounts of carotenoids, quinones, and BChl a. It has been
      suggested that carotenoids in chlorosomes provide photoprotection by rapidly
      quenching triplet excited states of BChl via a triplet-triplet energy transfer
      mechanism that prevents energy transfer to oxygen and the formation of harmful
      singlet oxygen. In this work we studied triplet energy transfer kinetics and
      photodegradation of chlorosomes isolated from wild-type Chlorobium tepidum and
      from genetically modified species with different types of carotenoids and from a
      carotenoid-free mutant. Supporting a photoprotective function of carotenoids,
      carotenoid-free chlorosomes photodegrade approximately 3 times faster than wild
      type chlorosomes. However, a significant fraction of the BChls forms a long
      lived, triplet-like state that does not interact with carotenoids or with oxygen.
      We propose that these states are triplet excitons that form due to triplet
      triplet interaction between the closely packed BChls. Numerical exciton
      simulations predict that the energy of these triplet excitons may fall below that
      of singlet oxygen and triplet carotenoids; this would prevent energy transfer
      from triplet BChl. Thus, the formation of triplet excitons in chlorosomes serves
      as an alternative photoprotection mechanism.

PMID- 17434949
TI  - The shape and dynamics of the Leptospiraceae.
AB  - Most swimming bacteria produce thrust by rotating helical filaments called
      flagella. Typically, the flagella stick out into the external fluid environment;
      however, in the spirochetes, a unique group that includes some highly pathogenic
      species of bacteria, the flagella are internalized, being incased in the
      periplasmic space; i.e., between the outer membrane and the cell wall. This
      coupling between the periplasmic flagella and the cell wall allows the flagella
      to serve a skeletal, as well as a motile, function. In this article, we propose a
      mathematical model for spirochete morphology based on the elastic interaction
      between the cell body and the periplasmic flagella. This model describes the
      mechanics of the composite structure of the cell cylinder and periplasmic
      flagella and accounts for the morphology of Leptospiraceae. This model predicts
      that the cell cylinder should be roughly seven times stiffer than the flagellum.
      In addition, we explore how rotation of the periplasmic flagellum deforms the
      cell cylinder during motility. We show that the transition between hook-shaped
      and spiral-shaped ends is purely a consequence of the change in direction of the
      flagellar motor and does not require flagellar polymorphism.

PMID- 17434950
TI  - On kinetics of phage adsorption.
AB  - Adsorption of lambda-phage on sensitive bacteria Escherichia coli is a classical
      problem but not all issues have been resolved. One of the outstanding problems is
      the rate of adsorption, which in some cases appears to exceed the theoretical
      limit imposed by the law of random diffusion. We revisit this problem by
      conducting experiments along with new theoretical analyses. Our measurements show
      that upon incubating lambda-phage with bacteria Ymel, the population of unbound
      phage in a salt buffer decreases with time and in general obeys a double
      exponential function characterized by a fast (tau(1)) and a slow (tau(2)) decay
      time. We found that both the fast and the slow processes are specific to
      interactions between lambda-phage and its receptor LamB. Such specificity
      motivates a kinetic model that describes the interaction between the phage and
      the receptor as an on-and-off process followed by an irreversible binding. The
      latter may be a signature of the initiation of DNA translocation. The kinetic
      model successfully predicts the double exponential behavior seen in the
      experiment and allows the corresponding rate constants to be extracted from
      single measurements. The weak temperature dependence of the reversible and the
      irreversible binding rate suggests that phage retention by the receptor is
      entropic in nature and that a molecular key-lock interaction may be an
      appropriate description of the interaction between the phage tail and the
      receptor.

PMID- 17434951
TI  - Systemic translocation of particulate matter-associated metals following a single
      intratracheal instillation in rats.
AB  - Respirable ambient particulate matter (PM) exposure has been associated with an
      increased risk of cardiovascular disease. Direct translocation of PM-associated
      metals from the lungs into systemic circulation may be partly responsible. We
      measured elemental content of lungs, plasma, heart, and liver of healthy male WKY
      rats (12-15 weeks old) 4 or 24 h following a single intratracheal (IT)
      instillation of saline or 8.33 mg/kg of oil combustion PM (HP-12) containing a
      variety of transition metals with differing water and acid solubility. Tissues
      were digested with a combination of quaternary acid, amine, and nitric acid and
      analyzed using inductively coupled plasma-atomic emission spectroscopy. Lung
      levels of metals were lower at 24 h than at 4 h. Metals with high water
      solubility and relatively high concentration in HP-12 were increased in
      extrapulmonary organs. Water-soluble nonessential metals, like vanadium and
      nickel, were increased in plasma, hearts, and livers of exposed animals at both
      time points. Exposure-related small increases in essential metals, like zinc and
      manganese, were also noted in extrapulmonary tissues at both time points. Lead,
      with low water solubility but high acid solubility, was detected in liver only at
      24-h postinstillation. Elements with low water or acid solubility, like silicon
      and aluminum, were not detected in extrapulmonary tissues despite decreased
      levels in the lung suggesting mucociliary clearance. We have shown that HP-12
      associated metals translocate to systemic circulation and extrapulmonary organs
      following IT exposure. This translocation is dependent upon their relative levels
      and water solubility. Thus, following inhalation, PM-associated metals deposited
      in the lung may be released into systemic circulation at different rates
      depending on their water/acid solubility, thereby providing a means by which
      metals may elicit direct extrapulmonary effects.

PMID- 17434952
TI  - Cyclophosphamide-induced apoptosis in COV434 human granulosa cells involves
      oxidative stress and glutathione depletion.
AB  - The anticancer drug cyclophosphamide induces granulosa cell apoptosis and is
      detoxified by glutathione (GSH) conjugation. We previously showed that both
      cyclophosphamide treatment and GSH depletion induced granulosa cell apoptosis in
      rats, but the role of GSH in apoptosis in human ovarian cells has not been
      studied. Using the COV434 human granulosa cell line, we tested the hypotheses
      that (1) GSH depletion or treatment with 4-hydroperoxycyclophosphamide (4HC), a
      preactivated form of cyclophosphamide, induces apoptosis, (2) GSH depletion
      potentiates 4HC-induced apoptosis, and (3) 4HC-induced apoptosis is mediated by
      GSH depletion and oxidative stress. Cells were treated with buthionine
      sulfoximine (BSO), a specific inhibitor of GSH synthesis, with or without
      follicle stimulating hormone (FSH) or serum. A significant increase in the number
      of apoptotic cells, assessed by terminal deoxynucleotidyl transferase-mediated
      deoxy-uridine triphosphate nick-end labeling (TUNEL) and Hoechst 33342 staining,
      occurred with BSO treatment. Treatment with 4HC dose-dependently induced
      apoptosis by TUNEL, Hoechst staining, and caspase 3 activation. Treatment with
      4HC caused an increase in reactive oxygen species generation, measured by
      dichlorofluorescein fluorescence, oxidative DNA damage, measured by 8
      hydroxyguanosine immunostaining, and an oxidation of the redox potential for the
      oxidized glutathione/reduced glutathione couple. Total intracellular GSH declined
      after 4HC treatment, preceding the onset of cell death. Treatment with
      antioxidants inhibited 4HC-induced apoptosis. Combined treatment with BSO and 4HC
      caused greater induction of apoptosis than either treatment alone. These findings
      are consistent with roles for oxidative stress and GSH depletion in mediating the
      induction of apoptosis in COV434 cells by cyclophosphamide.

PMID- 17434953
TI  - Polybrominated diphenyl ethers and ortho-substituted polychlorinated biphenyls as
      neuroendocrine disruptors of vasopressin release: effects during physiological
      activation in vitro and structure-activity relationships.
AB  - The neuropeptide, vasopressin (VP) is synthesized in magnocellular neuroendocrine
      cells (MNCs) located within the supraoptic (SON) and paraventricular (PVN) nuclei
      of the mammalian hypothalamus. VP has multiple functions including maintenance of
      body fluid homeostasis, cardiovascular control, learning and memory, and nervous
      system development. Polybrominated diphenyl ethers (PBDEs), used as additive
      flame retardants, have been shown to interfere with hormone metabolism and
      function. Previously, we demonstrated that the technical polychlorinated biphenyl
      (PCB) mixture, Aroclor 1254, inhibits somatodendritic VP release from the SON of
      osmotically stimulated rats. The objectives of the current study were to test
      whether PBDEs affect central VP release in a similar manner and to determine the
      potency of several PCB and PBDE congeners in order to identify a common mode of
      action for these persistent chemicals. The current work shows that the commercial
      PBDE mixture (DE-71) significantly decreased somatodendritic VP release from rat
      SON punches in a strain-independent manner. In addition, the specific congeners
      PBDE 47 and PCB 47 (15 and 5 microM) were also neuroactive in this system. To
      explore structure/activity relationships, we compared the effects of PBDE 77 with
      PCB 77. PBDE 77, but not PCB 77 significantly reduced VP release. These results
      show that like PCBs, PBDEs perturb signaling mechanisms responsible for hormone
      release, and that environmentally relevant PBDE congeners are more neuroactive
      than the commercial mixtures with noncoplanarity of these compounds playing a
      role in promoting neuroactivity.

PMID- 17434954
TI  - Effect of administration of intestinal anthelmintic drugs on haemoglobin:
      systematic review of randomised controlled trials.
AB  - OBJECTIVE: To evaluate the effect of routine administration of intestinal
      anthelmintic drugs on haemoglobin. DESIGN: Systematic review of randomised
      controlled trials. DATA SOURCES: Electronic databases and hand search of reviews,
      bibliographies of books, and abstracts and proceedings of international
      conferences. STUDY SELECTION: Included studies were randomised or quasi
      randomised controlled trials using an intestinal anthelmintic agent in the
      intervention group, in which haemoglobin was evaluated as an outcome measure.
      Trials in which treatment for schistosoma (praziquantel) was given exclusively to
      the intervention group were excluded. RESULTS: The search identified 14 eligible
      randomised controlled trials. Data were available for 7829 subjects, of whom 4107
      received an anthelmintic drug and 3722 received placebo. The pooled weighted mean
      difference (random effect model) of the change in haemoglobin was 1.71 (95%
      confidence interval 0.70 to 2.73) g/l (P<0.001; test for heterogeneity: Cochran
      Q=51.17, P<0.001; I(2)=61% (37% to 76%)). With the World Health Organization's
      recommended haemoglobin cut-offs of 120 g/l in adults and 110 g/l in children,
      the average estimated reduction in prevalence of anaemia ranged from 1.1% to
      12.4% in adults and from 4.4% to 21.0% in children. The estimated reductions in
      the prevalence of anaemia increased with lower haemoglobin cut-offs used to
      define anaemia. CONCLUSIONS: Routine administration of intestinal anthelmintic
      agents results in a marginal increase in haemoglobin (1.71 g/l), which could
      translate on a public health scale into a small (5% to 10%) reduction in the
      prevalence of anaemia in populations with a relatively high prevalence of
      intestinal helminthiasis.

PMID- 17434969
TI  - SigM-responsive genes of Bacillus subtilis and their promoters.
AB  - Promoters of nine Bacillus subtilis genes (bcrC, yacK, ydaH, yfnI, yjbD, ypbG,
      ypuA, yraA, and ysxA), all responsive to artificially induced increases in the
      stress-responsive extracytoplasmic function sigma factor, SigM, were mapped by
      rapid amplification of cDNA ends-PCR. The resulting promoter consensus suggests
      that overlapping control by SigX or SigW is common.

PMID- 17434970
TI  - The complex of Sphingomonas elodea ATCC 31461 glucose-1-phosphate
      uridylyltransferase with glucose-1-phosphate reveals a novel quaternary
      structure, unique among nucleoside diphosphate-sugar pyrophosphorylase members.
AB  - Gellan gum is a widely used commercial material, available in many different
      forms. Its economic importance has led to studies into the biosynthesis of
      exopolysaccharide gellan gum, which is industrially prepared in high yields using
      Sphingomonas elodea ATCC 31461. Glucose-1-phosphate uridylyltransferase mediates
      the reversible conversion of glucose-1-phosphate and UTP into UDP-glucose and
      pyrophosphate, which is a key step in the biosynthetic pathway of gellan gums.
      Here we present the X-ray crystal structure of the glucose-1-phosphate
      uridylyltransferase from S. elodea. The S. elodea enzyme shares strong monomeric
      similarity with glucose-1-phosphate thymidylyltransferase, several structures of
      which are known, although the quaternary structures of the active enzymes are
      rather different. A detailed comparison between S. elodea glucose-1-phosphate
      uridylyltransferase and available thymidylyltransferases is described and shows
      remarkable structural similarities, despite the low sequence identities between
      the two divergent groups of proteins.

PMID- 17434971
TI  - Role of chromosomal and plasmid-borne receptor homologues in the response of
      Bacillus megaterium QM B1551 spores to germinants.
AB  - Spores of Bacillus megaterium QM B1551 germinate in response to a number of
      trigger compounds, including glucose, proline, leucine, and inorganic salts. An
      approximate 6-kb region of the 165-kb plasmid was found to harbor a tricistronic
      receptor operon, gerU, and a monocistronic receptor component, gerVB. The gerU
      operon was observed to complement the germination response in plasmidless strain
      PV361 to glucose and leucine, with KBr acting as a cogerminant. Proline
      recognition is conferred by the monocistronic gerVB gene, the presence of which
      also improves the germination response to other single-trigger compounds. A
      chimeric receptor, GerU*, demonstrates interchangeability between receptor
      components and provides evidence that it is the B protein of the receptor that
      determines germinant specificity. Introduction of the gerU/gerVB gene cluster to
      B. megaterium KM extends the range of germinants recognized by this strain to
      include glucose, proline, and KBr in addition to alanine and leucine. A
      chromosomally encoded receptor, GerA, the B component of which is predicted to be
      truncated, was found to be functionally redundant. Similarly, the plasmid-borne
      antiporter gene, grmA, identified previously as being essential for germination
      in QM B1551, did not complement the germination defect in the plasmidless variant
      PV361. Wild-type spores carrying an insertion-deletion mutation in this cistron
      germinated normally; thus, the role of GrmA in spore germination needs to be
      reevaluated in this species.

PMID- 17434973
TI  - Blunted muscle vasodilatation during chemoreceptor stimulation in patients with
      heart failure.
AB  - Chemoreflex control of sympathetic nerve activity is exaggerated in heart failure
      (HF) patients. However, the vascular implications of the augmented sympathetic
      activity during chemoreceptor activation in patients with HF are unknown. We
      tested the hypothesis that the muscle blood flow responses during peripheral and
      central chemoreflex stimulation would be blunted in patients with HF. Sixteen
      patients with HF (49 +/- 3 years old, Functional Class II-III, New York Heart
      Association) and 11 age-paired normal controls were studied. The peripheral
      chemoreflex control was evaluated by inhalation of 10% O(2) and 90% N(2) for 3
      min. The central chemoreflex control was evaluated by inhalation of 7% CO(2) and
      93% O(2) for 3 min. Muscle sympathetic nerve activity (MSNA) was directly
      evaluated by microneurography. Forearm blood flow was evaluated by venous
      occlusion plethysmography. Baseline MSNA were significantly greater in HF
      patients (33 +/- 3 vs. 20 +/- 2 bursts/min, P = 0.001). Forearm vascular
      conductance (FVC) was not different between the groups. During hypoxia, the
      increase in MSNA was significantly greater in HF patients than in normal controls
      (9.0 +/- 1.6 vs. 0.8 +/- 2.0 bursts/min, P = 0.001). The increase in FVC was
      significantly lower in HF patients (0.00 +/- 0.10 vs. 0.76 +/- 0.25 units, P =
      0.001). During hypercapnia, MSNA responses were significantly greater in HF
      patients than in normal controls (13.9 +/- 3.2 vs. 2.1 +/- 1.9 bursts/min, P =
      0.001). FVC responses were significantly lower in HF patients (-0.29 +/- 0.10 vs.
      0.37 +/- 0.18 units, P = 0.001). In conclusion, muscle vasodilatation during
      peripheral and central chemoreceptor stimulation is blunted in HF patients. This
      vascular response seems to be explained, at least in part, by the exaggerated
      MSNA responses during hypoxia and hypercapnia.

PMID- 17434972
TI  - Membrane association and multimerization of TcpT, the cognate ATPase ortholog of
      the Vibrio cholerae toxin-coregulated-pilus biogenesis apparatus.
AB  - The toxin-coregulated pilus (TCP) is one of the major virulence factors of Vibrio
      cholerae. Biogenesis of this type 4 pilus (Tfp) requires a number of structural
      components encoded by the tcp operon. TcpT, the cognate putative ATPase, is
      required for TCP biogenesis and all TCP-mediated functions. We studied the
      stability and localization of TcpT in cells containing in-frame deletions in each
      of the tcp genes. TcpT was detectable in each of the biogenesis mutants except
      the DeltatcpT strain. TcpT was localized to the inner membrane (IM) in a TcpR
      dependent manner. TcpR is a predicted bitopic inner membrane protein of the TCP
      biogenesis apparatus. Using metal affinity pull-down experiments, we demonstrated
      interaction between TcpT and TcpR. Using Escherichia coli as a heterologous
      system, we investigated direct interaction between TcpR and TcpT. We report that
      TcpR is sufficient for TcpT IM localization per se; however, stable IM
      localization of TcpT requires an additional V. cholerae-specific factor(s). A
      LexA-based two-hybrid system was utilized to define interaction domains of the
      two proteins. We demonstrate a strong interaction between the cytoplasmic domain
      of TcpR and the N-terminal 100 amino acid residues of TcpT. We also demonstrated
      the ability of the C-terminal domain of TcpT to multimerize.

PMID- 17434974
TI  - Antiviral and myocyte protective effects of murine interferon-beta and -{alpha}2
      in coxsackievirus B3-induced myocarditis and epicarditis in Balb/c mice.
AB  - The present study tested the hypothesis that murine (m)IFN-beta or mIFN-alpha(2)
      can eliminate cardiac viral load and protect cardiomyocytes from injury in
      animals infected with coxsackievirus B3 (CVB3). CVB3-inoculated male Balb/c mice
      exhibited signs of illness, including lethargy, progressive weight loss, and
      death (10% on day 3 and 100% on day 8). Cardiac viral load was high [4,277 +/-
      1,009 plaque-forming units and 25 +/- 5 copies CVB3/hypoxanthine guanine
      phosphoribosyl transferase 1 mRNA] on day 4. The cardiac tissue exhibited severe
      inflammatory infiltration and myocyte damage with an average myocarditis
      integrated pathology score of 2.1 +/- 0.2 on day 7. Most of the mice infected
      with CVB3 also developed epicarditis, and 55% had intraventricular thrombi
      present. Treatment with mIFN-beta [2.5 to 10 million international units
      (MIU)/kg] dose-dependently improved the general health status in CVB3-inoculated
      mice, as evidenced by reduction in weight loss, prevention of death, elimination
      of cardiac viral load, protection of myocytes from injury, decrease in
      inflammatory cell infiltration, and attenuation of intraventricular thrombus
      formation. Treatment with 10 MIU/kg mIFN-alpha(2) resulted in a similar level of
      efficacy as that induced by 5 MIU/kg mIFN-beta, with the exception that mIFN
      alpha(2) did not reduce cardiac CVB3 mRNA. However, mIFN-alpha(2) , but not any
      dose group of mIFN-beta, significantly attenuated CVB3-induced epicarditis. These
      data demonstrate antiviral effects for both mIFN-beta and mIFN-alpha(2), which
      lead to protection of the mice from CVB3-induced myocarditis. However, the
      potential mechanisms leading to a differential host response for the two isoforms
      of mIFN remain to be elucidated.

PMID- 17434975
TI  - Ten-hour preservation of guinea pig isolated hearts perfused at low flow with air
      saturated Lifor solution at 26{degrees}C: comparison to ViaSpan solution.
AB  - There is no suitable solution to preserve hearts for longer than 5 h between
      donor explant and recipient implant. Lifor is a fully artificial preservation
      medium containing both a nonprotein oxygen and nutrient carrier (nanoparticles)
      and cellular nutrients, including amino acids and sugars. We proposed that
      recirculated Lifor solution would satisfactorily preserve guinea pig isolated
      hearts perfused at low flow with no added O(2) at room temperature for 10 h.
      Hearts were isolated from 21 guinea pigs and perfused with Krebs-Ringer (KR)
      solution (97% O(2) and 3% CO(2)) at 37 degrees C. Heart rate, inflow and outflow
      O(2) tension, coronary flow, left ventricular pressure (LVP), and maximal and
      minimal rate of change in LVP (dLVP/dt) were measured. After baseline
      measurements, hearts were perfused with recirculated Lifor or ViaSpan
      equilibrated with room air at 15% of control flow at 26 degrees C for 10 h.
      Hearts were then perfused at 100% flow with KR for 2 h at 37 degrees C. A time
      control (untreated) group was perfused only with KR solution for 15 h. Lifor
      arrested and protected hearts against diastolic contracture and maintained a low
      O(2) extraction. Compared with time controls, Lifor led to a higher developed LVP
      and coronary flow; %O(2) extraction and cardiac efficiency were similar between
      these two groups. Hearts similarly treated with ViaSpan exhibited diastolic
      contracture and lower %O(2) extraction during treatment and, upon reperfusion
      with KR, exhibited continued diastolic contracture, no return of heart rate or
      contractility, low coronary flow, low %O(2) extraction, and marked infarction.
      For long-term cardiac protection, a suitable preservation solution recirculated
      at low flow and room temperature without supplemental O(2) would reduce the
      support apparatus required for transport. Lifor was far superior to ViaSpan in
      meeting these requirements.

PMID- 17434976
TI  - Increased cardiac sympathetic nerve activity in heart failure is not due to
      desensitization of the arterial baroreflex.
AB  - Increased sympathetic drive to the heart worsens prognosis in heart failure, but
      the level of cardiac sympathetic nerve activity (CSNA) has been assessed only by
      indirect methods, which do not permit testing of whether its control by arterial
      baroreceptors is defective. To do this, CSNA was measured directly in 16 female
      sheep, 8 of which had been ventricularly paced at 200-220 beats/min for 4-6 wk,
      until their ejection fraction fell to between 35 and 40%. Recording electrodes
      were surgically implanted in the cardiac sympathetic nerves, and after 3 days'
      recovery the responses to intravenous phenylephrine and nitroprusside infusions
      were measured in conscious sheep. Electrophysiological recordings showed that
      resting CSNA (bursts/100 heartbeats) was significantly elevated in heart-failure
      sheep (89 +/- 3) compared with normal animals (46 +/- 6; P < 0.001). This
      increased CSNA was not accompanied by any increase in the low-frequency power of
      heart-rate variability. The baroreceptor-heart rate reflex was significantly
      depressed in heart failure (maximum gain -3.29 +/- 0.56 vs. -5.34 +/- 0.66
      beats.min(-1).mmHg(-1) in normal animals), confirming published findings. In
      contrast, the baroreflex control of CSNA was undiminished (maximum gain in heart
      failure -6.33 +/- 1.06 vs. -6.03 +/- 0.95%max/mmHg in normal sheep). Direct
      recordings in a sheep model of heart failure thus show that resting CSNA is
      strikingly increased, but this is not due to defective control by arterial
      baroreceptors.

PMID- 17434977
TI  - Dissociation between metabolic and vascular insulin resistance in aging.
AB  - Physiological actions of insulin via activation of the phosphatidylinositol 3
      kinase/Akt pathway in the endothelium serve to couple regulation of hemodynamic
      and metabolic homeostasis. Insulin resistance, endothelial dysfunction, and
      hypertension increase in prevalence with aging. We investigated the metabolic and
      endothelial actions of insulin in 24- vs. 3-mo Sprague-Dawley rats. With the use
      of the hyperinsulinemic euglycemic clamp, the rate of glucose infusion necessary
      to maintain equivalent plasma glucose (5.5 mmol/l) was similar in 24- vs. 3-mo
      rats, as was fasting glucose (5.2 +/- 0.33 vs. 4.4 +/- 0.37 mmol/l; mean +/- SE)
      and insulin (0.862 +/- 0.193 vs. 1.307 +/- 0.230 mg/l). Systolic blood pressure
      was higher in 24-mo rats (133 +/- 5 vs. 110 +/- 4 mmHg; P = 0.005). Endothelial
      nitric oxide (NO)-dependent relaxation to insulin was impaired in aortas of 24-
      vs. 3-mo rats (maximal response 8.9 +/- 4.3 vs. 34.9 +/- 3.9%; P = 0.002); N(G)
      nitro-l-arginine methyl ester abolished insulin-mediated relaxation in 3- but not
      24-mo rats. Endothelium NO-dependent (acetylcholine) and -independent (sodium
      nitroprusside) relaxation, as well as NADPH oxidase activity, were similar in 3-
      and 24-mo rats. Insulin increased aortic serine phosphorylation of Akt in 3-mo
      rats by 120% over 24-mo rats (P < 0.05) and serine phosphorylation of endothelial
      NO synthase (eNOS) in 3-mo rats by 380% over 24-mo rats (P < 0.05). Aortic
      expression of phosphorylated c-Jun NH(2)-terminal kinase-1 and serine
      phosphorylated insulin receptor substrate-1, known mediators of metabolic insulin
      resistance, was similar in 3- and 24-mo rats. Expression of caveolin-1, a
      regulator of eNOS activity and insulin signaling, was 55% lower in 24- than 3-mo
      rats (P = 0.002). In summary, impaired vasorelaxation to insulin in aging was
      independent of metabolic insulin sensitivity and associated with impaired insulin
      mediated activation of the Akt/eNOS pathway, but intact activation of the
      acetylcholine-mediated Ca(2+)-calmodulin/eNOS pathway. Vascular insulin
      resistance in aging may add to the increased susceptibility of this population to
      vascular injury induced by traditional cardiovascular risk factors.

PMID- 17434978
TI  - Dynamic changes in conduction velocity and gap junction properties during
      development of pacing-induced heart failure.
AB  - End-stage heart failure (HF) is characterized by changes in conduction velocity
      (CV) that predispose to arrhythmias. Here, we investigate the time course of
      conduction changes with respect to alterations in connexin 43 (Cx43) properties
      and mechanical function during the development of HF. We perform high-resolution
      optical mapping in arterially perfused myocardial preparations from dogs
      subjected to 0, 3, 7, 14, and 21 days of rapid pacing to produce variable degrees
      of remodeling. CV is compared with an index of mechanical function [left
      ventricular end-diastolic pressure (LVEDP)] and with dynamic changes in the
      expression, distribution, and phosphorylation of Cx43. In contrast to
      repolarization, CV was preserved during early stages of remodeling (3 and 7 days)
      and significantly reduced at later stages, which were associated with marked
      increases in LVEDP. Measurements of differentially phosphorylated Cx43 isoforms
      revealed early, sustained downregulation of pan-Cx43 that preceded changes in CV
      and LVEDP, a gradual rise in a dephosphorylated Cx43 isoform to over twofold
      baseline levels in end-stage HF, and a late abrupt increase in pan-Cx43, but not
      dephosphorylated Cx43, lateralization. These data demonstrate that 1) CV slowing
      occurs only at advanced stages of remodeling, 2) total reduction of pan-Cx43 is
      an early event that precedes mechanical dysfunction and CV slowing, 3) changes in
      Cx43 phosphorylation are more closely associated with the onset of HF, and 4)
      Cx43 lateralization is a late event that coincides with marked CV reduction.
      These data reveal a novel paradigm of remodeling based on the timing of
      conduction abnormalities relative to changes in Cx43 isoforms and mechanical
      dysfunction.

PMID- 17434979
TI  - Adaptation of coronary microvascular exchange in arterioles and venules to
      exercise training and a role for sex in determining permeability responses.
AB  - Studies of physical performance and energy metabolism during and following
      exercise have shown significant sex-specific musculoskeletal adaptations; less is
      known of vascular adaptations, particularly with respect to exchange capacity. In
      response to adenosine (ADO), a metabolite produced during exercise, permeability
      (P(s)) of coronary arterioles from female pigs changed acutely; the magnitude and
      direction of the change (Delta P(s)) were determined by training status. In the
      present study P(s) to albumin was assessed in arterioles (n = 138) and venules (n
      = 24) isolated from hearts of male (N = 27) and female (N = 59) pigs in the
      exercise training group (EX). We evaluated the hypothesis that coronary
      microvessel exchange adapts to endurance exercise training not by altering basal
      P(s), per se, but by elevating P(s) on exposure to ADO. In contrast, training
      resulted in a reduction of basal P(s) in all arterioles, and in venules from
      males, with no change in venules from EX females. Exposure to ADO resulted in the
      predicted increase in P(s) except for venules from EX males where P(s) was
      reduced. Delta P(s) responses of arterioles to mediators of adenylyl cyclase
      (isoproterenol)- and guanylyl cyclase (atrial natriuretic peptide)-signaling
      pathways were attenuated in EX pigs relative to pigs in the sedentary group. The
      adaptation of EX arterioles involves an upregulation of a nitric oxide-dependent
      pathway since nitric oxide synthase inhibition blocks Delta P(s) by ADO. Thus
      adaptation of microvascular exchange capacity to endurance exercise training not
      only occurs but also involves multiple mechanisms that differ in arterioles and
      venules with their relative contribution to net flux being a function of sex.

PMID- 17434981
TI  - Response of cardiac mast cells to atrial natriuretic peptide.
AB  - Previously, our laboratory demonstrated that cardiac mast cell degranulation
      induces adverse ventricular remodeling in response to chronic volume overload.
      The purpose of this study was to investigate whether atrial natriuretic peptide
      (ANP), which is known to be elevated in chronic volume overload, causes cardiac
      mast cell degranulation. Relative to control, ANP induced significant histamine
      release from peritoneal mast cells, whereas isolated cardiac mast cells were not
      responsive. Infusion of ANP (225 pg/ml) into blood-perfused isolated rat hearts
      produced minimal activation of cardiac mast cells, similar to that seen in the
      control group. ANP also did not increase matrix metalloproteinase-2 activity,
      reduce collagen volume fraction, or alter diastolic or systolic cardiac function
      compared with saline-treated controls. In a subsequent study to evaluate the
      effects of natriuretic peptide receptor antagonism on volume overload-induced
      ventricular remodeling, anantin was administered to rats with an aortocaval
      fistula. Comparable increases of myocardial MMP-2 activity in treated and
      untreated rats with an aortocaval fistula were associated with equivalent
      decreases in ventricular collagen (P < 0.05 vs. sham-operated controls). Cardiac
      functional parameters and left ventricular hypertrophy were unaffected by
      anantin. We conclude that ANP is not a cardiac mast cell secretagogue and is not
      responsible for the cardiac mast cell-mediated adverse ventricular remodeling in
      response to volume overload.

PMID- 17434982
TI  - Medroxyprogesterone acetate prevents the cardioprotective and anti-inflammatory
      effects of 17beta-estradiol in an in vivo model of myocardial ischemia and
      reperfusion.
AB  - Previous studies demonstrated the protective effects of estrogen administration
      in models of cardiovascular disease. However, there is a discrepancy between
      these data and those from the recent clinical trials with hormone replacement
      therapy in menopausal women. One possible explanation for the divergent results
      is the addition of progestin to the hormone regimen in the Women's Health
      Initiative and the Heart and Estrogen/Progestin Replacement Study trials. The aim
      of the present study was to examine the effects of a combination of 17beta
      estradiol (E(2), 20 microg) and medroxyprogesterone acetate (MPA, 80 microg) on
      infarct size in New Zealand White rabbits. Infarct size as a percentage of the
      area at risk was significantly reduced by administration of E(2) 30 min before
      induction of myocardial ischemia compared with vehicle (19.5 +/- 3.1 vs. 55.7 +/-
      2.6%, P < 0.001). However, E(2) + MPA failed to elicit a reduction in infarct
      size (52.5 +/- 4.6%), and MPA had no effect (50.8 +/- 2.6%). E(2) also reduced
      serum levels of cardiac troponin I, immune complex deposition in myocardial
      tissue, activation of the complement system, and lipid peroxidation. All these
      effects were reversed by MPA. The results suggest that MPA antagonizes the
      infarct-sparing effects of E(2), possibly through modulation of the immune
      response after ischemia and reperfusion.

PMID- 17434980
TI  - Decreased age-related cardiac dysfunction, myocardial nitrative stress,
      inflammatory gene expression, and apoptosis in mice lacking fatty acid amide
      hydrolase.
AB  - Recent studies have uncovered important cross talk between inflammation,
      generation of reactive oxygen and nitrogen species, and lipid metabolism in the
      pathogenesis of cardiovascular aging. Inhibition of the endocannabinoid
      anandamide metabolizing enzyme, the fatty acid amide hydrolase (FAAH), is
      emerging as a promising novel approach for the treatment of various inflammatory
      disorders. In this study, we have investigated the age-associated decline of
      cardiac function and changes in inflammatory gene expression, nitrative stress,
      and apoptosis in FAAH knockout (FAAH(-/-)) mice and their wild-type (FAAH(+/+))
      littermates. Additionally, we have explored the effects of anandamide on TNF
      alpha-induced ICAM-1 and VCAM-1 expression and monocyte-endothelial adhesion in
      human coronary artery endothelial cells (HCAECs). There was no difference in the
      cardiac function (measured by the pressure-volume conductance catheter system)
      between 2- to 3-mo-old (young) FAAH(-/-) and FAAH(+/+) mice. In contrast, the
      aging-associated decline in cardiac function and increased myocardial gene
      expression of TNF-alpha, gp91phox, matrix metalloproteinase (MMP)-2, MMP-9,
      caspase-3 and caspase-9, myocardial inducible nitric oxide synthase protein
      expression, nitrotyrosine formation, poly (ADP-ribose)polymerase cleavage and
      caspase-3/9 activity, observed in 28- to 31-mo-old (aging) FAAH(+/+) mice, were
      largely attenuated in knockouts. There was no difference in the myocardial
      cannabinoid CB(1) and CB(2) receptor gene expression between young and aging
      FAAH(-/-) and FAAH(+/+) mice. Anandamide dose dependently attenuated the TNF
      alpha-induced ICAM-1 and VCAM-1 expression, NF-kappaB activation in HCAECs, and
      the adhesion of monocytes to HCAECs in a CB(1)- and CB(2)-dependent manner. These
      findings suggest that pharmacological inhibition of FAAH may represent a novel
      protective strategy against chronic inflammation, oxidative/nitrative stress, and
      apoptosis associated with cardiovascular aging and atherosclerosis.

PMID- 17434983
TI  - Effects of sterile pericarditis on connexins 40 and 43 in the atria: correlation
      with abnormal conduction and atrial arrhythmias.
AB  - The canine sterile pericarditis model is characterized by impaired conduction and
      atrial arrhythmia vulnerability. Electrical and structural remodeling processes
      caused by the inflammatory response likely promote these abnormalities. In the
      present study, we tested the hypothesis that altered distribution of atrial
      connexins is associated with markedly abnormal atrial conduction, thereby
      contributing to vulnerability to atrial flutter (AFL) and atrial fibrillation
      (AF) induction and maintenance. During rapid pacing and induced, sustained AFL or
      AF in five sterile pericarditis (SP) and five normal (NL) dogs, epicardial atrial
      electrograms were recorded simultaneously from both atria (380 electrodes) or
      from the right atrium (RA) and Bachmann's bundle (212 electrodes). Tissues from
      RA sites were subjected to immunostaining and immunoblotting to assess connexin
      (Cx) 40 and Cx43 distribution and expression. Transmural myocyte (alpha-actinin)
      and fibroblast (vimentin) volume were also assessed by immunostaining. RA pacing
      maps showed markedly abnormal conduction in SP, with uniform conduction in NL.
      Total RA activation time was significantly prolonged in SP vs. NL at 300-ms and
      200-ms pacing-cycle lengths. Sustained arrhythmias were only inducible in SP
      [total: 4/5 (AFL: 3/5; AF: 1/5)]. In NL, Cx40, Cx43, alpha-actinin, and vimentin
      were homogeneously distributed transmurally. In SP, Cx40, Cx43, and alpha-actinin
      were absent epicardially, decreased midmyocardially, and normal endocardially. SP
      increased epicardial vimentin expression, suggesting fibroblast proliferation.
      Immunoblot analysis confirmed reduced expression of Cx40 and Cx43 in SP. The
      transmural gradient in the volume fraction of Cx40 and Cx43 in SP is associated
      with markedly abnormal atrial conduction and is likely an important factor in the
      vulnerability to induction and maintenance of AFL/AF in SP.

PMID- 17434984
TI  - Arabidopsis inositol polyphosphate 6-/3-kinase (AtIpk2beta) is involved in
      axillary shoot branching via auxin signaling.
AB  - The Arabidopsis (Arabidopsis thaliana) inositol polyphosphate 6-/3-kinase gene
      (AtIpk2beta) is known to participate in inositol phosphate metabolism. However,
      little is known about its physiological functions in higher plants. Here, we
      report that AtIpk2beta regulates Arabidopsis axillary shoot branching. By
      overexpressing AtIpk2beta in the wild type and mutants, we found that
      overexpression of AtIpk2beta leads to more axillary shoot branches. Further
      analysis of AtIpk2beta overexpression lines showed that axillary meristem forms
      earlier and the bud outgrowth rate is also accelerated, resulting in more
      axillary shoot branches. The AtIpk2beta promoter/beta-glucuronidase (GUS) fusion
      (AtIpk2betaGUS) expression pattern is similar to that of the auxin reporter
      DR5GUS. Moreover, AtIpk2beta can be induced in response to exogenous indole-3
      acetic acid (IAA) treatments. In addition, AtIpk2beta overexpression plants
      exhibit IAA-related phenotypes and are more resistant to exogenous IAA
      treatments. Further analysis employing reverse transcription-polymerase chain
      reaction shows that some genes, including auxin-biosynthesis (CYP83B1), auxin
      transport (PIN4), and auxin-mediated branching genes (MAX4 and SPS), are
      regulated by AtIpk2beta. Taken together, our data provide insights into a role
      for AtIpk2beta in axillary shoot branching through the auxin signaling pathway.

PMID- 17434985
TI  - Maize Y9 encodes a product essential for 15-cis-zeta-carotene isomerization.
AB  - Carotenoids are a diverse group of pigments found in plants, fungi, and bacteria.
      They serve essential functions in plants and provide health benefits for humans
      and animals. In plants, it was thought that conversion of the C40 carotenoid
      backbone, 15-cis-phytoene, to all-trans-lycopene, the geometrical isomer required
      by downstream enzymes, required two desaturases (phytoene desaturase and zeta
      carotene desaturase [ZDS]) plus a carotene isomerase (CRTISO), in addition to
      light-mediated photoisomerization of the 15-cis-double bond; bacteria employ only
      a single enzyme, CRTI. Characterization of the maize (Zea mays) pale yellow9 (y9)
      locus has brought to light a new isomerase required in plant carotenoid
      biosynthesis. We report that maize Y9 encodes a factor required for isomerase
      activity upstream of CRTISO, which we term Z-ISO, an activity that catalyzes the
      cis- to trans-conversion of the 15-cis-bond in 9,15,9'-tri-cis-zeta-carotene, the
      product of phytoene desaturase, to form 9,9'-di-cis-zeta-carotene, the substrate
      of ZDS. We show that recessive y9 alleles condition accumulation of 9,15,9'-tri
      cis-zeta-carotene in dark tissues, such as roots and etiolated leaves, in
      contrast to accumulation of 9,9'-di-cis-zeta-carotene in a ZDS mutant,
      viviparous9. We also identify a locus in Euglena gracilis, which is similarly
      required for Z-ISO activity. These data, taken together with the geometrical
      isomer substrate requirement of ZDS in evolutionarily distant plants, suggest
      that Z-ISO activity is not unique to maize, but will be found in all higher
      plants. Further analysis of this new gene-controlled step is critical to
      understanding regulation of this essential biosynthetic pathway.

PMID- 17434986
TI  - tie-dyed1 Functions non-cell autonomously to control carbohydrate accumulation in
      maize leaves.
AB  - The tie-dyed1 (tdy1) mutant of maize (Zea mays) produces chlorotic, anthocyanin
      accumulating regions in leaves due to the hyperaccumulation of carbohydrates.
      Based on the nonclonal pattern, we propose that the accumulation of sucrose (Suc)
      or another sugar induces the tdy1 phenotype. The boundaries of regions expressing
      the tdy1 phenotype frequently occur at lateral veins. This suggests that lateral
      veins act to limit the expansion of tdy1 phenotypic regions by transporting Suc
      out of the tissue. Double mutant studies between tdy1 and chloroplast-impaired
      mutants demonstrate that functional chloroplasts are needed to generate the Suc
      that induces the tdy1 phenotype. However, we also found that albino cells can
      express the tdy1 phenotype and overaccumulate Suc imported from neighboring green
      tissues. To characterize the site and mode of action of Tdy1, we performed a
      clonal mosaic analysis. In the transverse dimension, we localized the function of
      Tdy1 to the innermost leaf layer. Additionally, we determined that if this layer
      lacks Tdy1, Suc can accumulate, move into adjacent genetically wild-type layers,
      and induce tdy1 phenotypic expression. In the lateral dimension, we observed that
      a tdy1 phenotypic region did not reach the mosaic sector boundary, suggesting
      that wild-type Tdy1 acts non-cell autonomously and exerts a short-range
      compensatory effect on neighboring mutant tissue. A model proposing that Tdy1
      functions in the vasculature to sense high concentrations of sugar, up-regulate
      Suc transport into veins, and promote tissue differentiation and function is
      discussed.

PMID- 17434987
TI  - Apyrases (nucleoside triphosphate-diphosphohydrolases) play a key role in growth
      control in Arabidopsis.
AB  - Expression of two Arabidopsis (Arabidopsis thaliana) apyrase (nucleoside
      triphosphate-diphosphohydrolase) genes with high similarity, APY1 and APY2, was
      analyzed during seedling development and under different light treatments using
      beta-glucuronidase fusion constructs with the promoters of both genes. As
      evaluated by beta-glucuronidase staining and independently confirmed by other
      methods, the highest expression of both apyrases was in rapidly growing tissues
      and/or tissues that accumulate high auxin levels. Red-light treatment of
      etiolated seedlings suppressed the protein and message level of both apyrases at
      least as rapidly as it inhibited hypocotyl growth. Adult apy1 and apy2 single
      mutants had near-normal growth, but apy1apy2 double-knockout plants were dwarf,
      due primarily to reduced cell elongation. Pollen tubes and etiolated hypocotyls
      overexpressing an apyrase had faster growth rates than wild-type plants. Growing
      pollen tubes released ATP into the growth medium and suppression of apyrase
      activity by antiapyrase antibodies or by inhibitors simultaneously increased
      medium ATP levels and inhibited pollen tube growth. These results imply that APY1
      and APY2, like their homologs in animals, act to reduce the concentration of
      extracellular nucleotides, and that this function is important for the regulation
      of growth in Arabidopsis.

PMID- 17434988
TI  - Genetic dissection of histidine biosynthesis in Arabidopsis.
AB  - The biosynthesis of histidine (His) in microorganisms, long studied through the
      isolation and characterization of auxotrophic mutants, has emerged as a paradigm
      for the regulation of metabolism and gene expression. Much less is known about
      His biosynthesis in flowering plants. One limiting factor has been the absence of
      large collections of informative auxotrophs. We describe here the results of a
      systematic screen for His auxotrophs of Arabidopsis (Arabidopsis thaliana). Ten
      insertion mutants disrupted in four different biosynthetic genes (HISN2, HISN3,
      HISN4, HISN6A) were identified through a combination of forward and reverse
      genetics and were shown to exhibit an embryo-defective phenotype that could be
      rescued by watering heterozygous plants with His. Male transmission of the mutant
      allele was in several cases reduced. Knockouts of two redundant genes (HISN1B and
      HISN5A) had no visible phenotype. Another mutant blocked in the final step of His
      biosynthesis (hisn8) and a double mutant altered in the redundant first step of
      the pathway (hisn1a hisn1b) exhibited a combination of gametophytic and embryonic
      lethality in heterozygotes. Homozygous mutant seedlings and callus tissue
      produced from rescued seeds appeared normal when grown in the presence of His but
      typically senesced after continued growth in the absence of His. These knockout
      mutants document the importance of His biosynthesis for plant growth and
      development, provide valuable insights into amino acid transport and source-sink
      relationships during seed development, and represent a significant addition to
      the limited collection of well-characterized auxotrophs in flowering plants.

PMID- 17434989
TI  - A major quantitative trait locus for cadmium tolerance in Arabidopsis halleri
      colocalizes with HMA4, a gene encoding a heavy metal ATPase.
AB  - Cadmium (Cd) tolerance seems to be a constitutive species-level trait in
      Arabidopsis halleri sp. halleri. Therefore, an interspecific cross was made
      between A. halleri and its closest nontolerant interfertile relative, Arabidopsis
      lyrata sp. petraea, and a first-generation backcross population (BC1) was used to
      map quantitative trait loci (QTL) for Cd tolerance. Three QTL were identified,
      which explained 43%, 24%, and 16% of the phenotypic variation in the mapping
      population. Heavy metal transporting ATPases4 (HMA4), encoding a predicted heavy
      metal ATPase, colocalized with the peak of the major QTL Cdtol-1 and was
      consequently further studied. HMA4 transcripts levels were higher in the roots
      and the shoots of A. halleri than in A. lyrata sp. petraea. Furthermore, HMA4 was
      also more highly expressed in all BC1 genotypes harboring the HMA4 A. halleri
      allele at the QTL Cdtol-1, independently of the presence of an A. halleri allele
      at the two other QTL. Overexpression of AhHMA4 in yeast (Saccharomyces
      cerevisiae) supported a role of HMA4 in zinc (Zn) and Cd transport by reducing
      the Cd and Zn contents of the yeast cells. In epidermal tobacco (Nicotiana
      tabacum) cells, AhHMA4:green fluorescent protein was clearly localized in the
      plasma membrane. Taken together, all available data point to the elevated
      expression of HMA4 P(1B)-type ATPase as an efficient mechanism for improving
      Cd/Zn tolerance in plants under conditions of Cd/Zn excess by maintaining low
      cellular Cd(2+) and Zn(2+) concentrations in the cytoplasm.

PMID- 17434990
TI  - Flavone synthases from Medicago truncatula are flavanone-2-hydroxylases and are
      important for nodulation.
AB  - Flavones are important copigments found in the flowers of many higher plants and
      play a variety of roles in plant adaptation to stress. In Medicago species,
      flavones also act as signal molecules during symbiotic interaction with the
      diazotropic bacterium Sinorhizobium meliloti. They are the most potent nod gene
      inducers found in root exudates. However, flavone synthase II (FNS II), the key
      enzyme responsible for flavone biosynthesis, has not been characterized in
      Medicago species. We cloned two FNS II genes from Medicago truncatula using known
      FNS II sequences from other species and named them MtFNSII-1 and MtFNSII-2.
      Functional assays in yeast (Saccharomyces cerevisiae) suggested that the
      catalytic mechanisms of both cytochrome P450 monooxygenases were similar to the
      other known legume FNS II from licorice (Glycyrrhiza echinata). MtFNSII converted
      flavanones to 2-hydroxyflavanones instead of flavones whereas FNS II from the
      nonlegume Gerbera hybrida, converted flavanones to flavones directly. The two
      MtFNSII genes had distinct tissue-specific expression patterns. MtFNSII-1 was
      highly expressed in roots and seeds whereas MtFNSII-2 was highly expressed in
      flowers and siliques. In addition, MtFNSII-2 was inducible by S. meliloti and
      methyl jasmonate treatment, whereas MtFNSII-1 was not. Histochemical staining of
      transgenic hairy roots carrying the promoter-reporter constructs indicated that
      the MtFNSII-2 induction was tissue specific, mostly localized to vascular tissues
      and root hairs. RNA interference-mediated suppression of MtFNSII genes resulted
      in flavone depleted roots and led to significantly reduced nodulation when
      inoculated with S. meliloti. Our results provide genetic evidence supporting that
      flavones are important for nodulation in M. truncatula.

PMID- 17434991
TI  - The structure of two N-methyltransferases from the caffeine biosynthetic pathway.
AB  - Caffeine (1,3,7-trimethylxanthine) is a secondary metabolite produced by certain
      plant species and an important component of coffee (Coffea arabica and Coffea
      canephora) and tea (Camellia sinensis). Here we describe the structures of two S
      adenosyl-l-methionine-dependent N-methyltransferases that mediate caffeine
      biosynthesis in C. canephora 'robusta', xanthosine (XR) methyltransferase (XMT),
      and 1,7-dimethylxanthine methyltransferase (DXMT). Both were cocrystallized with
      the demethylated cofactor, S-adenosyl-L-cysteine, and substrate, either
      xanthosine or theobromine. Our structures reveal several elements that appear
      critical for substrate selectivity. Serine-316 in XMT appears central to the
      recognition of XR. Likewise, a change from glutamine-161 in XMT to histidine-160
      in DXMT is likely to have catalytic consequences. A phenylalanine-266 to
      isoleucine-266 change in DXMT is also likely to be crucial for the discrimination
      between mono and dimethyl transferases in coffee. These key residues are probably
      functionally important and will guide future studies with implications for the
      biosynthesis of caffeine and its derivatives in plants.

PMID- 17434992
TI  - Mutations in LACS2, a long-chain acyl-coenzyme A synthetase, enhance
      susceptibility to avirulent Pseudomonas syringae but confer resistance to
      Botrytis cinerea in Arabidopsis.
AB  - We identified an Arabidopsis (Arabidopsis thaliana) mutant, sma4 (symptoms to
      multiple avr genotypes4), that displays severe disease symptoms when inoculated
      with avirulent strains of Pseudomonas syringae pv tomato, although bacterial
      growth is only moderately enhanced compared to wild-type plants. The sma4 mutant
      showed a normal susceptible phenotype to the biotrophic fungal pathogen Erysiphe
      cichoracearum. Significantly, the sma4 mutant was highly resistant to a
      necrotrophic fungal pathogen, Botrytis cinerea. Germination of B. cinerea spores
      on sma4 mutant leaves was inhibited, and penetration by those that did germinate
      was rare. The sma4 mutant also showed several pleiotropic phenotypes, including
      increased sensitivity to lower humidity and salt stress. Isolation of SMA4 by
      positional cloning revealed that it encodes LACS2, a member of the long-chain
      acyl-CoA synthetases. LACS2 has previously been shown to be involved in cutin
      biosynthesis. We therefore tested three additional cutin-defective mutants for
      resistance to B. cinerea: att1 (for aberrant induction of type three genes),
      bodyguard, and lacerata. All three displayed an enhanced resistance to B.
      cinerea. Our results indicate that plant cutin or cuticle structure may play a
      crucial role in tolerance to biotic and abiotic stress and in the pathogenesis of
      B. cinerea.

PMID- 17434993
TI  - The acropetal wave of developmental cell death of tobacco corolla is preceded by
      activation of transglutaminase in different cell compartments.
AB  - The activity of transglutaminase (TGase), an enzyme responsible for polyamine
      conjugation to proteins, was analyzed in relationship to developmental cell death
      (DCD) during the flower life span stages of the tobacco (Nicotiana tabacum)
      corolla. As the DCD exhibits an acropetal gradient, TGase was studied in corolla
      proximal, medial, and distal parts. TGase was immunorecognized by three TGase
      antibodies; the main 58-kD band decreased during corolla life, whereas a 38-kD
      band localized progressively from basal to distal parts. The former was present
      in the soluble, microsomal, plastidial (together with the 38-kD band), and cell
      wall fractions. The endogenous TGase activity increased during DCD reaching a
      maximum soon after the corolla opening. The activity maximum shifted from
      proximal to distal part, preceding the DCD acropetal pattern. A similar activity
      increase was observed by the exogenous TGase substrate (histidine(6)-Xpr-green
      fluorescent protein). Subcellular activities were detected in (1) the microsomes,
      where TGase activity is in general higher in the proximal part, peaking at the
      corolla opening; (2) the soluble fraction, where it is present only in the
      proximal part at senescence; (3) the plastids, where it shows an increasing
      trend; and (4) cell walls, prevailing in the distal part and progressively
      increasing. These data suggest a relationship between DCD and TGase; the latter,
      possibly released in the cell wall through the Golgi vesicles, could cooperate to
      cell wall strengthening, especially at the abscission zone and possibly during
      corolla shape change. The plastid TGase, stabilizing the photosystems, could
      sustain the energy requirements for the senescence progression.

PMID- 17434995
TI  - Differential regulation of sorbitol and sucrose loading into the phloem of
      Plantago major in response to salt stress.
AB  - Several plant families generate polyols, the reduced form of monosaccharides, as
      one of their primary photosynthetic products. Together with sucrose (Suc) or
      raffinose, these polyols are used for long-distance allocation of
      photosynthetically fixed carbon in the phloem. Many species from these families
      accumulate these polyols under salt or drought stress, and the underlying
      regulation of polyol biosynthetic or oxidizing enzymes has been studied in
      detail. Here, we present results on the differential regulation of genes that
      encode transport proteins involved in phloem loading with sorbitol and Suc under
      salt stress. In the Suc- and sorbitol-translocating species Plantago major, the
      mRNA levels of the vascular sorbitol transporters PmPLT1 and PmPLT2 are rapidly
      up-regulated in response to salt treatment. In contrast, mRNA levels for the
      phloem Suc transporter PmSUC2 stay constant during the initial phase of salt
      treatment and are down-regulated after 24 h of salt stress. This adaptation in
      phloem loading is paralleled by a down-regulation of mRNA levels for a predicted
      sorbitol dehydrogenase (PmSDH1) in the entire leaf and of mRNA levels for a
      predicted Suc phosphate synthase (PmSPS1) in the vasculature. Analyses of Suc and
      sorbitol concentrations in leaves, in enriched vascular tissue, and in phloem
      exudates of detached leaves revealed an accumulation of sorbitol and, to a lesser
      extent, of Suc within the leaves of salt-stressed plants, a reduced rate of
      phloem sap exudation after NaCl treatment, and an increased sorbitol-to-Suc ratio
      within the phloem sap. Thus, the up-regulation of PmPLT1 and PmPLT2 expression
      upon salt stress results in a preferred loading of sorbitol into the phloem of P.
      major.

PMID- 17434994
TI  - Comprehensive transcriptome profiling in tomato reveals a role for
      glycosyltransferase in Mi-mediated nematode resistance.
AB  - Root-knot nematode (RKN; Meloidogyne spp.) is a major crop pathogen worldwide.
      Effective resistance exists for a few plant species, including that conditioned
      by Mi in tomato (Solanum lycopersicum). We interrogated the root transcriptome of
      the resistant (Mi+) and susceptible (Mi-) cultivars 'Motelle' and 'Moneymaker,'
      respectively, during a time-course infection by the Mi-susceptible RKN species
      Meloidogyne incognita and the Mi-resistant species Meloidogyne hapla. In the
      absence of RKN infection, only a single significantly regulated gene, encoding a
      glycosyltransferase, was detected. However, RKN infection influenced the
      expression of broad suites of genes; more than half of the probes on the array
      identified differential gene regulation between infected and uninfected root
      tissue at some stage of RKN infection. We discovered 217 genes regulated during
      the time of RKN infection corresponding to establishment of feeding sites, and 58
      genes that exhibited differential regulation in resistant roots compared to
      uninfected roots, including the glycosyltransferase. Using virus-induced gene
      silencing to silence the expression of this gene restored susceptibility to M.
      incognita in 'Motelle,' indicating that this gene is necessary for resistance to
      RKN. Collectively, our data provide a picture of global gene expression changes
      in roots during compatible and incompatible associations with RKN, and point to
      candidates for further investigation.

PMID- 17434996
TI  - Quorum sensing enhances the stress response in Vibrio cholerae.
AB  - Vibrio cholerae lives in aquatic environments and causes cholera. Here, we show
      that quorum sensing enhances V. cholerae viability under certain stress
      conditions by upregulating the expression of RpoS, and this regulation acts
      through HapR, suggesting that a quorum-sensing-enhanced stress response plays a
      role in V. cholerae environmental survival.

PMID- 17434997
TI  - Kinetics and metabolism of Bifidobacterium adolescentis MB 239 growing on
      glucose, galactose, lactose, and galactooligosaccharides.
AB  - The kinetics and the metabolism of Bifidobacterium adolescentis MB 239 growing on
      galactooligosaccharides (GOS), lactose, galactose, and glucose were investigated.
      An unstructured unsegregated model for growth in batch cultures was developed,
      and kinetic parameters were calculated with a recursive algorithm. The growth
      rate and cellular yield were highest on galactose, followed by lactose and GOS,
      and were lowest on glucose. Lactate, acetate, and ethanol yields allowed the
      calculation of carbon fluxes toward fermentation products. Distributions between
      two- and three-carbon products were similar on all the carbohydrates (55 and 45%,
      respectively), but ethanol yields were different on glucose, GOS, lactose, and
      galactose, in decreasing order of production. Based on the stoichiometry of the
      fructose-6-phosphate shunt and on the carbon distribution among the products, the
      ATP yield was calculated. The highest yield was obtained on galactose, while the
      yields were 5, 8, and 25% lower on lactose, GOS, and glucose, respectively.
      Therefore, a correspondence among ethanol production, low ATP yields, and low
      biomass production was established, demonstrating that carbohydrate preferences
      may result from different distributions of carbon fluxes through the fermentative
      pathway. During the fermentation of a GOS mixture, substrate selectivity based on
      the degree of polymerization was exhibited, since lactose and the trisaccharide
      were the first to be consumed, while a delay was observed until longer
      oligosaccharides were utilized. Throughout the growth on both lactose and GOS,
      galactose accumulated in the cultural broth, suggesting that beta(1-4)
      galactosides can be hydrolyzed before they are taken up.

PMID- 17434998
TI  - New insights into the Enterococcus faecalis CroRS two-component system obtained
      using a differential-display random arbitrarily primed PCR approach.
AB  - Using a modified random arbitrarily primed PCR approach, the operon encoding the
      Enterococcus faecalis JH2-2 CroRS two-component regulatory system was shown to be
      repressed during stationary phase, and a CroRS-regulated operon (glnQHMP) was
      identified. Gel retardation assays showed that the CroR regulator binds
      specifically to the glnQHMP promoter.

PMID- 17434999
TI  - Functional analysis of D-alanylation of lipoteichoic acid in the probiotic strain
      Lactobacillus rhamnosus GG.
AB  - Lipoteichoic acid (LTA) is a macroamphiphile molecule which performs several
      functions in gram-positive bacteria, such as maintenance of cell wall
      homeostasis. D-alanylation of LTA requires the proteins encoded by the dlt
      operon, and this process is directly related to the charge properties of this
      polymer strongly contributing to its function. The insertional inactivation of
      dltD of the probiotic strain Lactobacillus rhamnosus GG (ATCC 53103) resulted in
      the complete absence of D-alanyl esters in the LTA as confirmed by nuclear
      magnetic resonance analysis. This was reflected in modifications of the bacterial
      cell surface properties. The dltD strain showed 2.4-fold-increased cell length, a
      low survival capacity in response to gastric juice challenge, an increased
      sensitivity to human beta-defensin-2, an increased rate of autolysis, an
      increased capacity to initiate growth in the presence of an anionic detergent,
      and a decreased capacity to initiate growth in the presence of cationic peptides
      compared to wild-type results. However, in vitro experiments revealed no major
      differences for adhesion to human intestinal epithelial cells, biofilm formation,
      and immunomodulation. These properties are considered to be important for
      probiotics. The role of the dlt operon in lactobacilli is discussed in view of
      these results.

PMID- 17435000
TI  - Signal mimics derived from a metagenomic analysis of the gypsy moth gut
      microbiota.
AB  - Bacterial signaling is an important part of community life, but little is known
      about the signal transduction pathways of the as-yet-uncultured members of
      microbial communities. To address this gap, we aimed to identify genes directing
      the synthesis of signals in uncultured bacteria associated with the midguts of
      gypsy moth larvae. We constructed a metagenomic library consisting of DNA
      extracted directly from the midgut microbiota and analyzed it using an
      intracellular screen designated METREX, which detects inducers of quorum sensing.
      In this screen, the metagenomic DNA and a biosensor reside in the same cell. The
      biosensor consists of a quorum-sensing promoter, which requires an acylhomoserine
      lactone or other small molecule ligand for activation, driving the expression of
      the reporter gene gfp. We identified an active metagenomic clone encoding a
      monooxygenase homologue that mediates a pathway of indole oxidation that leads to
      the production of a quorum-sensing inducing compound. The signal from this clone
      induces the activities of LuxR from Vibrio fischeri and CviR from Chromobacterium
      violaceum. This study is the first to identify a new structural class of quorum
      sensing inducer from uncultured bacteria.

PMID- 17435001
TI  - UV light inactivation of Mycobacterium avium subsp. paratuberculosis in milk as
      assessed by FASTPlaqueTB phage assay and culture.
AB  - UV light inactivation of Mycobacterium avium subsp. paratuberculosis in
      Middlebrook 7H9 broth and whole and semiskim milk was investigated using a
      laboratory-scale UV machine that incorporated static mixers within UV-penetrable
      pipes. UV treatment proved to be less effective in killing M. avium subsp.
      paratuberculosis suspended in milk (0.5- to 1.0-log(10) reduction per 1,000
      mJ/ml) than that suspended in Middlebrook 7H9 broth (2.5- to 3.3-log(10)
      reduction per 1,000 mJ/ml). The FASTPlaqueTB phage assay provided more rapid
      enumeration of surviving M. avium subsp. paratuberculosis (within 24 h) than
      culture on Herrold's egg yolk medium (6 to 8 weeks). Despite the fact that plaque
      counts were consistently 1 to 2 log(10) lower than colony counts throughout the
      study, UV inactivation rates for M. avium subsp. paratuberculosis derived using
      the phage assay and culture results were not significantly different (P = 0.077).

PMID- 17435002
TI  - Flavobacteria blooms in four eutrophic lakes: linking population dynamics of
      freshwater bacterioplankton to resource availability.
AB  - Heterotrophic bacteria are major contributors to biogeochemical cycles and
      influence water quality. Still, the lack of representative isolates and the few
      quantitative surveys leave the ecological role and significance of single
      bacterial populations to be revealed. Here we analyzed the diversity and dynamics
      of freshwater Flavobacteria populations in four eutrophic temperate lakes. From
      each lake, clone libraries were constructed using primers specific for either the
      class Flavobacteria or Bacteria. Sequencing of 194 Flavobacteria clones from 8
      libraries revealed a diverse freshwater Flavobacteria community and distinct
      differences among lakes. Abundance and seasonal dynamics of Flavobacteria were
      assessed by quantitative PCR with class-specific primers. In parallel, the
      dynamics of individual populations within the Flavobacteria community were
      assessed with terminal restriction fragment length polymorphism analysis using
      identical primers. The contribution of Flavobacteria to the total
      bacterioplankton community ranged from 0.4 to almost 100% (average, 24%). Blooms
      where Flavobacteria represented more than 30% of the bacterioplankton were
      observed at different times in the four lakes. In general, high proportions of
      Flavobacteria appeared during episodes of high bacterial production. Phylogenetic
      analyses combined with Flavobacteria community fingerprints suggested dominance
      of two Flavobacteria lineages. Both drastic alterations in total Flavobacteria
      and in community composition of this class significantly correlated with
      bacterial production, emphasizing that resource availability is an important
      driver of heterotrophic bacterial succession in eutrophic lakes.

PMID- 17435003
TI  - Phylogenetic analysis of deformed wing virus genotypes from diverse geographic
      origins indicates recent global distribution of the virus.
AB  - Honeybees originating from 10 different countries (Austria, Poland, Germany,
      Hungary, Slovenia, Nepal, Sri Lanka, the United Arab Emirates, Canada, and New
      Zealand) located on four continents were analyzed for the presence of deformed
      wing virus (DWV) nucleic acid by reverse transcription-PCR. Two target regions
      within the DWV genome were selected for PCR amplification and subsequent
      sequencing, i.e., a region within the putative VP2 and VP4 structural-protein
      genes and a region within the RNA helicase enzyme gene. DWV nucleic acid was
      amplified from 34 honeybee samples representing all the above-mentioned countries
      with the notable exception of New Zealand. The amplification products were
      sequenced, and phylogenetic analyses of both genomic regions were performed
      independently. The phylogenetic analyses included all sequences determined in
      this study as well as previously published DWV sequences and the sequences of two
      closely related viruses, Kakugo virus (KGV) and Varroa destructor virus 1 (VDV
      1). In the sequenced regions, the DWV genome turned out to be highly conserved,
      independent of the geographic origins of the honeybee samples: the partial
      sequences exhibited 98 to 99% nucleotide sequence identity. Substitutions were
      most frequently observed at the same positions in the various DWV sequences. Due
      to the high level of sequence conservation, no significant clustering of the
      samples in the phylogenetic trees could be identified. On the other hand, the
      phylogenetic analyses support a genetic segregation of KGV and VDV-1 from DWV.

PMID- 17435004
TI  - Purification, characterization, gene cloning, and expression of a novel alcohol
      dehydrogenase with anti-prelog stereospecificity from Candida parapsilosis.
AB  - An alcohol dehydrogenase from Candida parapsilosis CCTCC M203011 was
      characterized along with its biochemical activity and structural gene. The amino
      acid sequence shows similarity to those of the short-chain
      dehydrogenase/reductases but no overall identity to known proteins. This enzyme
      with unusual stereospecificity catalyzes an anti-Prelog reduction of 2
      hydroxyacetophenone to (S)-1-phenyl-1,2-ethanediol.

PMID- 17435005
TI  - Identification of anaerobic selenate-respiring bacteria from aquatic sediments.
AB  - The diversity population of microorganisms with the capability to use selenate as
      a terminal electron acceptor, reducing it to selenite and elemental selenium by
      the process known as dissimilatory selenate reduction, is largely unknown. The
      overall objective of this study was to gain an in-depth understanding of
      anaerobic biotransformation of selenium in the environment, particularly
      anaerobic respiration, and to characterize the microorganisms catalyzing this
      process. Here, we demonstrate the isolation and characterization of four novel
      anaerobic dissimilatory selenate-respiring bacteria enriched from a variety of
      sources, including sediments from three different water bodies in Chennai, India,
      and a tidal estuary in New Jersey. Strains S5 and S7 from India, strain KM from
      the Meadowlands, NJ, and strain pn1, categorized as a laboratory contaminant,
      were all phylogenetically distinct, belonging to various phyla in the bacterial
      domain. The 16S rRNA gene sequence shows that strain S5 constitutes a new genus
      belonging to Chrysiogenetes, while strain S7 belongs to the Deferribacteres, with
      greater than 98% 16S rRNA gene similarity to Geovibrio ferrireducens. Strain KM
      is related to Malonomonas rubra, Pelobacter acidigallici, and Desulfuromusa spp.,
      with 96 to 97% 16S rRNA gene similarity. Strain pn1 is 99% similar to Pseudomonas
      stutzeri. Strains S5, S7, and KM are obligately anaerobic selenate-respiring
      microorganisms, while strain pn1 is facultatively anaerobic. Besides respiring
      selenate, all these strains also respire nitrate.

PMID- 17435006
TI  - Attenuation of phospholipid signaling provides a novel mechanism for the action
      of valproic acid.
AB  - Valproic acid (VPA) is used to treat epilepsy and bipolar disorder and to prevent
      migraine. It is also undergoing trials for cancer therapy. However, the
      biochemical and molecular biological actions of VPA are poorly understood. Using
      the social amoeba Dictyostelium discoideum, we show that an acute effect of VPA
      is the inhibition of chemotactic cell movement, a process partially dependent
      upon phospholipid signaling. Analysis of this process shows that VPA attenuates
      the signal-induced translocation of PH(Crac)-green fluorescent protein from
      cytosol to membrane, suggesting the inhibition of phosphatidylinositol-(3,4,5)
      trisphosphate (PIP(3)) production. Direct labeling of lipids in vivo also shows a
      reduction in PIP and PIP(2) phosphorylation following VPA treatment. We further
      show that VPA acutely reduces endocytosis and exocytosis-processes previously
      shown to be dependent upon PIP(3) production. These results suggest that in
      Dictyostelium, VPA rapidly attenuates phospholipid signaling to reduce endocytic
      trafficking. To examine this effect in a mammalian model, we also tested
      depolarization-dependent neurotransmitter release in rat nerve terminals, and we
      show that this process is also suppressed upon application of VPA and an
      inhibitor of phosphatidylinositol 3-kinase. Although a more comprehensive
      analysis of the effect of VPA on lipid signaling will be necessary in mammalian
      systems, these results suggest that VPA may function to reduce phospholipid
      signaling processes and thus may provide a novel therapeutic effect for this
      drug.

PMID- 17435007
TI  - Acclimation to singlet oxygen stress in Chlamydomonas reinhardtii.
AB  - In an aerobic environment, responding to oxidative cues is critical for
      physiological adaptation (acclimation) to changing environmental conditions. The
      unicellular alga Chlamydomonas reinhardtii was tested for the ability to
      acclimate to specific forms of oxidative stress. Acclimation was defined as the
      ability of a sublethal pretreatment with a reactive oxygen species to activate
      defense responses that subsequently enhance survival of that stress. C.
      reinhardtii exhibited a strong acclimation response to rose bengal, a
      photosensitizing dye that produces singlet oxygen. This acclimation was dependent
      upon photosensitization and occurred only when pretreatment was administered in
      the light. Shifting cells from low light to high light also enhanced resistance
      to singlet oxygen, suggesting an overlap in high-light and singlet oxygen
      response pathways. Microarray analysis of RNA levels indicated that a relatively
      small number of genes respond to sublethal levels of singlet oxygen. Constitutive
      overexpression of either of two such genes, a glutathione peroxidase gene and a
      glutathione S-transferase gene, was sufficient to enhance singlet oxygen
      resistance. Escherichia coli and Saccharomyces cerevisiae exhibit well-defined
      responses to reactive oxygen but did not acclimate to singlet oxygen, possibly
      reflecting the relative importance of singlet oxygen stress for photosynthetic
      organisms.

PMID- 17435008
TI  - Evidence that noncoding RNA dutA is a multicopy suppressor of Dictyostelium
      discoideum STAT protein Dd-STATa.
AB  - Dd-STATa, a Dictyostelium discoideum homologue of metazoan STAT transcription
      factors, is necessary for culmination. We created a mutant strain with partial Dd
      STATa activity and used it to screen for unlinked suppressor genes. We screened
      approximately 450,000 clones from a slug-stage cDNA library for their ability to
      rescue the culmination defect when overexpressed. There were 12 multicopy
      suppressors of Dd-STATa, of which 4 encoded segments of a known noncoding RNA,
      dutA. Expression of dutA is specific to the pstA zone, the region where Dd-STATa
      is activated. In suppressed strains the expression patterns of several putative
      Dd-STATa target genes become similar to the wild-type strain. In addition, the
      amount of the tyrosine-phosphorylated form of Dd-STATa is significantly increased
      in the suppressed strain. These results indicate that partial copies of dutA may
      act upstream of Dd-STATa to regulate tyrosine phosphorylation by an unknown
      mechanism.

PMID- 17435009
TI  - Mcp4, a meiotic coiled-coil protein, plays a role in F-actin positioning during
      Schizosaccharomyces pombe meiosis.
AB  - Some meiosis-specific proteins of Schizosaccharomyces pombe harbor coiled-coil
      motifs and play essential roles in meiotic progression. Here we describe Mcp4, a
      novel meiosis-specific protein whose expression is abruptly induced at the
      horsetail phase and which remains expressed until sporulation is finished.
      Fluorescence microscopic analysis revealed that Mcp4 alters its subcellular
      localization during meiosis in a manner that partially resembles the movement of
      F-actin during meiosis. Mcp4 and F-actin never colocalize; rather, they are
      located in a side-by-side manner. When forespore membrane formation begins at
      metaphase II, the Mcp4 signals assemble at the lagging face of the dividing
      nuclei. At this stage, they are sandwiched between F-actin and the nucleus. Mcp4,
      in turn, appears to sandwich F-actin with Meu14. In mcp4Delta cells at anaphase
      II, the F-actin, which is normally dumbbell-shaped, adopts an abnormal balloon
      shape. Spores of mcp4Delta cells were sensitive to NaCl, although their shape and
      viability were normal. Taken together, we conclude that Mcp4 plays a role in the
      accurate positioning of F-actin during S. pombe meiosis.

PMID- 17435011
TI  - Effects of thermal manipulation during early and late embryogenesis on
      thermotolerance and breast muscle characteristics in broiler chickens.
AB  - Genetic selection has significantly improved the muscle development of fast
      growing broiler chickens in the last 50 yr. However, improvement in muscle growth
      has coincided with relatively poor development of visceral systems, resulting in
      impaired ability to cope with high environmental temperatures. The aim of this
      study was to elucidate the effects of thermal manipulation (TM) during different
      periods of embryogenesis on chick hatchability, BW and thermoregulation upon
      hatching, on their ability to cope with thermal challenge at 42 d of age, and on
      carcass and breast meat traits. Control embryos were incubated at 37.8 degrees C.
      The TM embryos were incubated at 37.8 degrees C and treated for 3 h at 39.5
      degrees C on the following days of embryogenesis: E8 to E10 [early (EA)], E16 to
      E18 [late (LA)], and both E8 to E10 and E16 to E18 (EA-LA). Body weight and body
      temperature (T(b)) were measured at hatching and throughout the growth period as
      well as during exposure of 42-d-old chickens to a thermal challenge at 35 degrees
      C for 6 h. The LA and EA chicks exhibited significantly lower T(b) than control
      chicks (37.9 vs. 38.2 degrees C) at hatching, but during the growth period,
      differences in T(b) between treated and control chicks decreased with age.
      Significant hyperthermia (over 44 degrees C) was monitored in all groups during
      the thermal challenge, but mortality was higher in treated than in control
      chickens. No effect of treatments on BW was found during the entire growth
      period. However, breast yield was higher in LA chickens than in controls at
      slaughter. The EA and EA-LA treatments slightly decreased the ultimate pH of
      breast meat, whereas the LA treatment had no effect. In conclusion, none of the
      TM conditions tested in the present study were able to improve long-term
      thermotolerance in chickens. Late treatment favored breast muscle growth without
      affecting ultimate pH and drip loss of breast meat.

PMID- 17435012
TI  - Comparison of in vitro fermentation and molecular microbial profiles of high
      fiber feed substrates incubated with chicken cecal inocula.
AB  - High fiber and nonstarch polysaccharide-based poultry diets have received more
      interest recently for retaining or promoting beneficial gastrointestinal
      microbial populations. The objective of this study was to investigate and compare
      the in vitro potential fermentability of high-fiber feed substrates (HFFS) by
      laying hen cecal microflora. Feed sources examined included soybean meal, soybean
      hull, beet pulp, wheat middlings, ground sorghum, cottonseed meal, 100% alfalfa
      meal, 90% alfalfa + 10% commercial layer ration, 80% alfalfa + 20% commercial
      layer ration, and 70% alfalfa + 30% commercial layer ration. Cecal contents and
      HFFS were incubated anaerobically in serum tubes at 39 degrees C for 24 h.
      Samples from 2 trials were analyzed at 0 and 24 h for short-chain fatty acids
      (SCFA). Short-chain fatty acids in samples at 0 h were subtracted from 24-h
      samples to determine the net production of SCFA. In both trials involving HFFS
      incubations with cecal inocula, acetate production was highest followed by
      propionate and butyrate whereas isobutyrate and isovalerate production were in
      trace amounts. In trial 2, detectable valerate production appeared to
      consistently occur with alfalfa-based HFFS. It was clear that SCFA production was
      largely dependent upon HFFS, because cecal inoculum alone yielded little or no
      detectable SCFA production. For HFFS incubations without cecal inocula, acetate
      production was highest; propionate and butyrate were similar, and isobutyrate,
      valerate, and isovalerate production were in trace amounts. Polymerase chain
      reaction-based denaturing gradient gel electrophoresis results from both trials
      indicated 69 and 71% similarity for comparison of all feed mixtures in trials 1
      and 2, respectively. All alfalfa-based HFFS yielded a higher similarity
      coefficient in trial 2 than in trial 1 with a band pattern of 90% similarity;
      diets containing 90% alfalfa + 10% commercial layer ration and 80% alfalfa + 20%
      commercial layer ration in trial 2 formed a subgroup with a 94% microbial
      similarity coefficient. These data suggest that high fiber sources may contribute
      to the fermentation and microbial diversity that occurs in the ceca of laying
      hens.

PMID- 17435013
TI  - Development of ascites-resistant and ascites-susceptible broiler lines.
AB  - The rapid growth of modern broilers is associated with enhanced appetite and high
      metabolic rate and, consequently, high O(2) demand. Ascites syndrome (AS)
      develops in individuals that fail to fully supply the increasing demand for O(2)
      in their bodies under ascites-inducing conditions (AIC) such as high altitude or
      low temperatures. The tendency of broilers to develop AS is heritable, but
      efficacious selection against AS susceptibility (without affecting the normal
      expression of other important traits) requires identification of indirect
      selection criteria. In the present study, divergent AS-susceptible (AS-S) and AS
      resistant (AS-R) lines were developed to confirm the heritability of AS and to
      facilitate future detection of criteria for indirect selection against AS
      susceptibility. The base population consisted of 85 sire families with a mean of
      73 progeny per sire, reared in a commercial broiler house under low-challenge AIC
      (cold environment and pelleted feed). Chicks dying with AS manifestations were
      designated AS-susceptible, whereas the surviving birds were designated AS
      resistant. By the end of the trial (d 48), AS mortality had accumulated to 17.2%,
      but AS incidence per family (%ASF) ranged from 0 to 49%, with a high heritability
      (0.57). Parents of 7 families with very high %ASF produced the first generation
      (S(1)) of the AS-S line, and parents of 7 families with very low %ASF produced
      the S(1) of the AS-R line. The S(1) males and females reproduced generation S(2)
      of the selected lines, whereas additional S(1) males were tested under high
      challenge AIC (individual cages, cool wind, and pelleted feed). Progeny testing
      under this high-challenge AIC, followed by sib selection, was repeated in
      generations S(2) and S(3), resulting in a divergence of 86.6% in the incidence of
      AS between the AS-S (91.3%) and AS-R (4.7%) lines. The rapid genetic divergence,
      and family analysis of %ASF suggested that a single or few major genes are
      responsible for the difference between the 2 selected lines. These lines may
      facilitate more sensitive and effective genomic research aimed at detecting these
      genes or identifying the primary physiological cause of AS.

PMID- 17435014
TI  - Variance component and breeding value estimation for reproductive traits in
      laying hens using a Bayesian threshold model.
AB  - Variance components and breeding values were estimated for 3 reproductive traits
      in a pure line of White Leghorn laying hens. The traits were proportion of
      fertile eggs of eggs set, proportion of first quality chicks of eggs set, and
      proportion of first-quality chicks of fertile eggs. A total of 3,020 hens were
      tested up to 3 times over a period of 7 d. For the definition of the traits, each
      egg was scored for each trait either as 0 or 1. To account for the binomial
      distribution of the data, a Bayesian animal threshold model implemented in a
      Gibbs sampler was applied that considered the record of each egg set as a
      repeated observation of the hen. The estimated heritability was 0.067, 0.126, and
      0.136 for the traits proportion of fertile eggs of eggs set, proportion of first
      quality chicks of eggs set, and proportion of first-quality chicks of fertile
      eggs, respectively, and the SE were small. It was shown that the heritability
      estimates were substantially higher from their expected values based on linear
      models. This results in a higher genetic progress and consequently favors the
      applied Bayesian threshold model for a genetic evaluation of binomial distributed
      reproductive traits.

PMID- 17435015
TI  - Relationships of a transforming growth factor-beta2 single nucleotide
      polymorphism and messenger ribonucleic acid abundance with bone and production
      traits in chickens.
AB  - Osteoporosis is a serious problem for the laying hen industry with economic,
      production, and welfare consequences. Transforming growth factor-beta2 (TGFbeta2)
      has been implicated as an important factor in coupling bone resorption and
      formation in bone remodeling. The current study was designed to determine if
      TGFbeta2 was associated with variation in bone mineralization in chickens, using
      2 complementary experimental approaches. First, an intronic single nucleotide
      polymorphism (SNP) present in TGFbeta2 was investigated in an F(2) population to
      determine its association with bone, growth, and egg traits of importance to the
      layer and broiler industries. The TGFbeta2 SNP was significantly associated (P <
      0.05) with bone mineral density and content. However, these associations became
      nonsignificant when BW was included as a covariate in analyses. The TGFbeta2 SNP
      was also significantly associated (P < 0.05) with BW from 1 to 6 wk of age and
      egg production from 46 to 55 wk of age. To further explore the relationship
      between TGFbeta2 and bone strength, bone marrow TGFbeta2 mRNA abundance was
      compared between broiler and layer chickens at 15, 35, and 60 wk of age. Bone and
      egg traits were measured along with mRNA abundance at each age and found to
      differ significantly between lines. The TGFbeta2 mRNA abundance was approximately
      4-fold greater in broiler compared with layer hens at 15 wk of age but was
      similar between lines at later ages. Thus, even though the TGFbeta2 SNP will
      likely not be an effective marker for improving bone strength independently of
      changes in BW, further research is warranted to investigate the relationship of
      TGFbeta2 mRNA abundance to bone strength in laying hens.

PMID- 17435016
TI  - Polymorphism of growth-correlated genes associated with fatness and muscle fiber
      traits in chickens.
AB  - Thirty single nucleotide polymorphisms (SNP) and one 6-bp insertion-deletion
      (indel) from 8 genes of somatotropic axis were used to study the association with
      chicken fatness and muscle fibers. The allele frequency difference between
      Xinghua and White Plymouth Rock chickens was observed, and their effects on
      fatness and muscle fiber traits were also evaluated by linkage analyses. The
      G143831A (G+1705A) SNP of the growth hormone (GH) gene was related to fat width,
      and the G144762A (G+119A) SNP of the GH gene was significantly associated with
      abdominal fat pad weight, abdominal fat pad ratio, and crude fatty content of the
      breast muscle. The 6-bp indel of the growth hormone secretagogue receptor (GHSR)
      gene was significantly linked with the fat traits. The C51978309T SNP of the
      insulin-like factor-I (IGF-I) gene was significantly linked with the transversal
      area of the leg muscle fiber and transversal area of the breast muscle fiber.
      There was significant linkage between the insulin (INS) gene and 2 traits of the
      transversal area of transversal area of the leg muscle fiber and transversal area
      of the breast muscle fiber. Association of 30 SNP and one 6-bp indel from 8 genes
      of somatotropic axis with chicken fatness and muscle fiber traits was analyzed in
      the present study. The GH, GHSR, and leptin receptor genes were significantly
      related to chicken fatness. The INS and IGF-I genes were linked with muscle fiber
      density. Therefore, the genes of somatotropic axis not only affected chicken
      growth and body composition but also were associated with fatness and muscle
      fiber traits.

PMID- 17435017
TI  - Effect of mast cell degranulation on chicken ileal ion transport in vitro.
AB  - Histamine is a primary mediator of the inflammatory response in mammals.
      Degranulation of intestinal mast cells results in the release of mast cell
      mediators such as histamine. Histamine stimulates epithelial ion transport in a
      range of mammalian tissues via specific histamine receptors. The aim of this
      study was to assess a potential role of tissue mast cells and of exogenous
      histamine in the regulation of ion transport in avian mucosa. Broiler chicken
      ileal histamine release and secretory responses to mast cell degranulation were
      determined in vitro with the use of ELISA and Ussing chamber techniques.
      Pharmacological degranulation of mucosal mast cells using compound 48/80 (15
      microg/mL) resulted in histamine release and an immediate-onset transient
      increase in transmural short-circuit current. The response to compound 48/80 was
      subject to tachyphylaxis and was significantly reduced in the presence of the
      histamine H(1) antagonist mepyramine, but was unaffected by the cyclooxygenase
      inhibitor piroxicam. Prior incubation with the mast cell stabilizer ketotifen
      prevented compound 48/80-induced increase in transmural short-circuit current. In
      conclusion, degranulation of avian intestinal mast cells would appear to result
      in histamine release that stimulates epithelial ion transport via histamine H(1)
      receptor activation. Although prostaglandin E(2) is a potent secretagogue in the
      avian small intestine epithelium, prostanoid production appears to have little
      role to play in mast cell-mediated epithelial ion transport.

PMID- 17435018
TI  - The effect of low-density diets on broiler breeder performance during the laying
      period and on embryonic development of their offspring.
AB  - The effect of low-density diets on bird performance, egg composition, and
      embryonic development was studied with 2,100 female and 210 male Cobb broiler
      breeders from 25 to 60 wk of age. The experiment included 5 treatments. These
      included a control group with a normal density diet (ND, 2,800 kcal of AME/kg).
      Treatments 2 (LD11) and 3 (LD21) had a 11 and 21% lower nutrient density.
      Treatment 4 (LD11(OP)) had a 11% less dense diet, which was obtained by inclusion
      of other feed ingredients. In these 4 treatments similar diets were given during
      the rearing and the laying period. Treatment 5 combined LD12 in the rearing
      period and ND diets during the laying period (LD12-ND). Egg composition and
      embryonic development were measured in eggs of ND and LD21 birds at 29 and 41 wk
      of age. During the laying period from wk 25 to 60, live weights did not differ
      among treatments, except that birds fed LD11(OP) had lower live weights. A
      significantly higher rate of lay was provided by LD11 compared with ND. Egg
      weights were significantly higher when low-density diets were fed, particularly
      in LD11(OP). Percentage of fertile eggs did not differ among treatments. Compared
      with the other treatments, LD11(OP) provided a significantly lower hatchability.
      We found that LD21 resulted in a better development of the area vitellina externa
      and heart and embryo weight at 29 wk of age. It was concluded that this was
      related to a higher egg weight and egg white proportion. This suggests that the
      amount of egg white in eggs of hens fed ND was limiting for embryonic
      development, particularly in eggs of young broiler breeders.

PMID- 17435019
TI  - The determination of retainable phosphorus, relative biological availability, and
      relative biological value of phosphorus sources for broilers.
AB  - A 10- to 21-d chick bioassay was conducted to determine the absolute retention
      value (ARV) for 2 different defluorinated phosphates (DF-1 and DF-2) and a
      reagent grade dicalcium phosphate (DCP). The total and test P in excreta
      regressed on feed P levels were subjected to general straight-line (linear), 1
      slope broken-line, 2-slope broken-line, and polynomial regression methods to find
      the best analysis model. The relative biological availability (RBA) and relative
      biological value (RBV) for P from the 2 different defluorinated phosphates (DF-1
      and DF-2) were obtained by the slope ratio method using 3 different bone
      measurements (% tibia ash, tibia breaking force, tibia weight) and RBV calculated
      using percentage tibia ash, weight gain, and feed/gain. The DCP was used as
      reference standard for RBA and RBV. The ARV measured at the breakpoints for test
      P by 2-slope analysis were determined to be 82.99% for DCP, 76.34% for DF-1, and
      70.30% for DF-2. The ARV of test P determined at 0.45% NPP was 62.41% for DCP,
      63.58% for DF-1, and 59.25% for DF-2. The relationship of ARV and RBA were
      similar in that DCP was 6% higher in ARV at the breakpoint compared with DF-1 and
      the RBA of DF-1 was 71 and 91% from tibia weight and tibia breaking force,
      respectively, compared with the bone parameters from chicks fed DCP. The DF-1
      phosphate had 3 and 7% higher ARV at the breakpoint and 0.45% NPP, respectively,
      compared with DF-2. The RBA of DF-2 was 59 and 80% from tibia weight and bone
      breaking force. The ARV of phosphate sources were independent of an arbitrary
      reference. The ARV for P sources provide retainable P information for industry
      based feed formulation that can reduce excess P in poultry waste. The excreta P
      data from broilers fed increasing levels of DCP indicates that the data are best
      described statistically with a 1-slope broken-line regression, 2-slope broken
      line regression, or polynomial regression.

PMID- 17435020
TI  - Effect of molting method and dietary energy on postmolt performance, egg
      components, egg solid, and egg quality in Bovans White and Dekalb White hens
      during second cycle phases two and three.
AB  - Two experiments of 4 x 2 x 2 factorial arrangements of 4 dietary energy levels, 2
      molting methods (feed withdrawal and no salt diet), and 2 strains (Bovans White
      and Dekalb White) were conducted to determine the effect of dietary energy and
      molting method on long-term postmolt performance of 2 strains of commercial
      Leghorns. In experiments 1 and 2, Bovans White hens (n = 576) and Dekalb White
      hens (n = 576) were randomly divided into 16 treatments (6 replicates of 12 birds
      per treatment). Experiment 1 lasted from 86 to 96 wk of age, and experiment 2
      lasted from 100 to 110 wk of age. Bovans White hens had significantly higher egg
      production than Dekalb White hens, whereas Bovans White hens had significantly
      lower egg weight, percentage of eggshell, and egg specific gravity than Dekalb
      White hens. Based on improved feed conversion, dietary energy of 2,846 kcal of
      ME/kg appeared to be enough for optimal performance during second cycle phase 2.
      Based on BW of hens, dietary energy level for optimal performance should be less
      than 2,936 kcal of ME/kg during second cycle phase 3. There can be no fixed ideal
      dietary energy level for optimal profits for postmolt egg production. Molting
      method had no effect on egg production and egg mass during the early and middle
      stages of the postmolt production period. However, hens molted by feed withdrawal
      had significantly higher egg production and egg mass during the later stage of
      the postmolt production period compared with hens molted by a no salt diet. There
      was no significant difference in egg specific gravity due to molting method.
      Feeding a no salt diet resulted in reasonable long-term postmolt performance and
      eggshell quality, rather than optimal performance and eggshell quality.

PMID- 17435021
TI  - Determining the methionine activity of Mintrex organic trace minerals in broiler
      chicks by using radiolabel tracing or growth assay.
AB  - Mintrex Zn, Mintrex Cu, and Mintrex Mn organic trace minerals contain 16% Zn, 15%
      Cu, and 13% Mn with 80, 78, and 76% 2-hydroxy-4-(methylthio)butanoic acid (HMTBA)
      by weight as the organic ligand, respectively. Our objective was to determine if
      HMTBA from Mintrex was fully available as a Met source. In experiment 1, thirty
      six broilers (7 to 10 d old) were orally gavaged with methyl-(14)C-labeled HMTBA,
      either as free HMTBA (Alimet feed supplement) or Zn bis(-2-hydroxy-4
      methylthiobutyrate) (Mintrex Zn). Radiolabel incorporation from either source
      into protein was measured as a marker of bioavailable Met activity. Results
      demonstrated that the HMTBA from Mintrex Zn was equally available as free HMTBA
      to support protein synthesis. In experiment 2, five hundred seventy-six 1-d-old
      broilers were allotted to 12 dietary treatments (TRT) for a 21-d growth assay. A
      TSAA-deficient diet containing 0.70% total TSAA (TRT 1) was supplemented with
      0.05, 0.10, 0.15, and 0.20% free HMTBA (TRT 2 to 5) to establish the standard Met
      response curve. Treatment 6 was analogous to TRT 2 but had an additional 160 ppm
      Zn, 80 ppm Cu, and 160 ppm Mn as sulfates. Treatments 7 to 12 were identical to
      TRT 2 but supplemented with 40 or 160 ppm Zn from Mintrex Zn, 20 or 80 ppm Cu
      from Mintrex Cu, or 40 or 160 ppm Mn from Mintrex Mn, respectively. For TRT 1
      through 6, growth performance increased due to increasing Met addition (P < 0.01)
      but not to increasing inorganic trace minerals. For Mintrex Zn, Cu, and Mn (TRT 7
      to 12), there was a linear increase in cumulative gain:feed ratio (P < 0.04), and
      for Mintrex Zn and Mn, there was a linear increase in cumulative gain (P < 0.03)
      to increasing Mintrex addition. A 1-slope broken-line model was used to calculate
      bioavailable Met activity from Mintrex for comparison with actual intake values.
      Results indicated that HMTBA from Mintrex was fully available as a Met source.

PMID- 17435022
TI  - Gene expression of manganese-containing superoxide dismutase as a biomarker of
      manganese bioavailability for manganese sources in broilers.
AB  - The goal of this study was to determine whether Mn-containing superoxide
      dismutase (MnSOD) gene expression in heart tissue would reflect differences among
      bioavailabilities of Mn sources earlier than other indices. Broilers were divided
      into 5 groups and fed a Mn-unsupplemented basal diet (control) or the basal diet
      supplemented with 120 mg of Mn/kg as Mn sulfate or Mn methionine E (Mn Met E), Mn
      amino acid B (Mn AA B), or Mn amino acid C (Mn AA C) with weak, moderate, or
      strong chelation strength, respectively. Heart MnSOD mRNA levels were analyzed
      using quantitative reverse transcription-PCR at 7, 14, or 21 d. The results
      showed that heart MnSOD mRNA level increased as dietary Mn level increased at any
      age. At 7 d, chicks fed the diet supplemented with Mn AA B had higher MnSOD mRNA
      levels than those fed the diet supplemented with Mn sulfate and Mn Met E, and the
      same tendency was observed at 14 or 21 d. The results suggest that MnSOD gene
      expression, which is regulated by dietary Mn at transcriptional level, could
      reflect differences among bio-availabilities of organic Mn sources as early as 7
      d. Therefore, the estimation of relative bioavailabilities of Mn sources based on
      heart MnSOD mRNA level could require a shorter experimental period and a smaller
      number of animals, and thus less cost.

PMID- 17435023
TI  - Further investigations on the role of diet-induced thermogenesis in the
      regulation of feed intake in chickens: comparison of age-matched broiler versus
      layer cockerels.
AB  - The aim of this study was to investigate the role of diet-induced thermogenesis
      (DIT) in the regulation of feed intake in age-matched broiler and layer
      cockerels. In addition, the effect of genotype on endocrine functioning and key
      metabolites of the intermediary metabolism as well as on the expression of
      muscular uncoupling protein (avUCP) was explored. One-day-old male broiler (Ross)
      and layer (ISA Brown) chicks were reared under standard conditions on commercial
      broiler starter and finisher diets. From 22 d of age, twice per week, 3 broiler
      and 6 layer cockerels were placed in open circuit respiratory chambers. After
      adaptation, the animals were feed-deprived for 24 h, and heat production was
      measured by indirect calorimetry. During the subsequent 7-h refeeding period,
      feed intake and DIT were measured. Blood samples were taken after feed
      deprivation and re-feeding. Muscle samples were taken after refeeding for
      determination of avUCP expression. A significantly higher heat production per
      metabolic BW (MBW) in the layer compared with the broiler cockerels, independent
      of nutritional state, suggests that the broilers used a greater proportion of the
      metabolizable energy intake for growth. The DIT per MBW and per gram of feed
      intake was higher for the layer than for the broiler cockerels. However, feed
      intake per MBW was also significantly higher in the layer cockerels. Thus, no
      feedback effect of DIT on feed intake per MBW was observed, and the model
      formulated for adult mammals relating feed intake to DIT could not be
      corroborated. The muscular expression of avUCP was not different between
      genotypes, which does not support the hypothesis of an involvement of avUCP in
      the higher DIT measured in layer cockerels. Circulating uric acid, glucose,
      triglyceride, and free fatty acid levels were significantly elevated in the layer
      compared with the broiler cockerels. As the diet was formulated according to
      broiler requirements, the higher metabolite levels of the layer cockerels might
      reflect a relative oversupply of dietary nutrients.

PMID- 17435024
TI  - Blood gas, hemoglobin, and growth of Tibetan chicken embryos incubated at high
      altitude.
AB  - Metabolism and hatchability are impaired when chicken eggs laid at sea level are
      incubated at high altitude. The Tibetan chicken is an excellent local poultry
      breed that inhabits altitudes of 2,900 m and has a hatchability of approximately
      75% at that altitude. To understand how Tibetan chicken embryos develop
      successfully at high altitude, we compared blood gas, pH, hemoglobin
      concentrations and embryo mass for Tibetan chicken embryos (T) and for embryos
      from a dwarf breed (D) that normally is reared at sea level. The 2 breeds (T and
      D) and 2 incubation altitudes (2,900 m = high, H; and 100 m = low, L) were
      compared at 9, 12, 15, and 18 d of incubation. Embryo weights were lower for the
      high altitude groups (TH, DH) than for the low altitude groups at all stages of
      incubation. The embryo mass of TH appeared to increase more quickly than that of
      DH. Compared with DH, TH embryos had lower arterialized oxygen partial pressure
      on d 18, higher venous carbon dioxide partial pressure from d 12 to 18, and
      higher hemoglobin concentration and lower venous blood pH values on d 12 and 15.
      These findings indicate that the ability of the Tibetan chicken embryos to adapt
      to the high altitude may be due to the increase in hemoglobin concentration,
      which augments the blood oxygen-carrying capacity. In addition, the higher venous
      carbon dioxide partial pressure and lower venous blood pH promote unloading of
      oxygen from hemoglobin.

PMID- 17435025
TI  - Endothelin 1, its endothelin type A receptor, connective tissue growth factor,
      platelet-derived growth factor, and adrenomedullin expression in lungs of
      pulmonary hypertensive and nonhypertensive chickens.
AB  - Twenty-four 1-d-old broilers were distributed in 2 groups, pulmonary hypertensive
      broilers (PHB) and pulmonary nonhypertensive broilers (NPHB), to estimate
      possible differences between them in the expression of endothelin 1 (ET-1) and
      its type A receptor, connective tissue growth factor, platelet-derived growth
      factor, and adrenomedullin expression in the lungs. For this purpose, total RNA
      extraction and real-time PCR analysis were used. Endothelin 1 mRNA levels in the
      lungs of PHB were significantly higher than the corresponding level in NPHB (P <
      0.001). In contrast, the opposite was true for ET-1 type A receptor mRNA levels
      (P < 0.001). Connective tissue growth factor mRNA levels in the lungs of PHB were
      significantly higher than in the lungs of NPHB (P < 0.01). However, no
      differences were encountered between the 2 groups of broilers in platelet-derived
      growth factor mRNA expression (P > 0.05). Adrenomedullin mRNA levels in the lungs
      of PHB were significantly higher than in NPHB (P < 0.01). It has been
      demonstrated for the first time that ET-1, connective tissue growth factor, and
      adrenomedullin are upregulated in the lungs of PHB. Furthermore, it is suggested
      that these peptides may play a major role in pulmonary hypertension
      pathophysiology. Present data might provide clues for future research directions
      such as genetic selection and therapeutic intervention to revert the process of
      pulmonary vasoconstriction and vascular remodeling. Major research goals could be
      to find endothelium-derived factors that probably trigger endothelial
      dysfunction, as well as possible interactions with already identified molecules
      which also intervene in the pulmonary response to hypoxia.

PMID- 17435026
TI  - Effects of photoperiod on ovarian morphology and carcass traits at sexual
      maturity in pullets.
AB  - This paper is concerned with the effects of photoperiod on ovarian morphology and
      carcass traits at sexual maturity in egg-type hens. Two hundred fifty-six
      commercial egg-type pullets were initially subjected to a photoperiod of 23L:1D,
      which was reduced to 22L:2D at 1 wk, to 18L:6D at 2 wk, and to 16L:8D at 3 wk.
      From 4 to 20 wk, the photoperiod was 8L:16D. At 20 wk, 32 pullets were
      individually caged in individually lit cages, with 8 cages per unit. Two cage
      units were placed into 4 photoperiods of 17L:7D, 15L:9D, 13L:11D, and 11L:13D,
      respectively. Each bird was processed when it reached sexual maturity (SM), and
      carcass and ovarian morphology were assessed. The results showed that photoperiod
      had an effect on the timing of SM, and the age at first egg was 5.7 d earlier for
      hens exposed to the 17L:7D photoperiod than the 11L:13D photoperiod. However,
      photoperiod had no effect on BW at SM. A photoperiod of 11L:13D limited ovarian
      follicle formation and increased carcass protein and lipid compared with birds on
      longer photoperiods, whereas the 17L:7D photoperiod restricted ovary and oviduct
      full development. These results indicated that excessively long and short
      photoperiods can restrict reproductive development in egg-type hens.

PMID- 17435027
TI  - Gastrointestinal maturation is accelerated in turkey poults supplemented with a
      mannan-oligosaccharide yeast extract (Alphamune).
AB  - Alphamune, a yeast extract antibiotic alternative, has been shown to stimulate
      the immune system, increase BW in pigs, and reduce Salmonella colonization in
      chickens. The influence of Alphamune on gastrointestinal tract development has
      not been reported. Two trials were conducted to evaluate the effects of Alphamune
      on gut maturation of 7- and 21-d-old turkey poults. Poults were fed a standard
      control unmedicated turkey starter diet or the same diet supplemented with either
      1 or 2 lb/ton of Alphamune (n = 18/group). Poults were weighed on d 7 and 21,
      euthanized, and a 2-cm section was collected from the midpoint of the duodenum,
      jejunum, and ileum of each bird (9 poults/d per treatment) and fixed in a 10%
      formalin solution for 72 h and then stained. Twenty measurements of villus
      height, villus surface area, lamina propria thickness, crypt depth, and density
      of neutral, sialomucin, and sulfomucin goblet cells were taken per section per
      poult. On d 7, BW were higher for the poults given the Alphamune treatments
      compared with control poults; however, no differences were observed on d 21.
      Alphamune supplementation influenced intestinal morphology differently based on
      gut location. Ileum villus height, surface area, lamina propria thickness, crypt
      depth, and neutral, sialomucin, and sulfomucin goblet cell density were enhanced
      with Alphamune treatments on d 7 and 21 (P < 0.05) and in a dose-dependent manner
      for many of the parameters evaluated. Jejunum results were mixed. Surface area,
      crypt depth, and sialomucin and sulfomucin goblet cells were consistently higher
      for the 2 lb/ton of Alphamune groups compared with the control group on d 7 and
      21. Duodenum villus height, surface area, and goblet cell density were higher for
      the 2 lb/ton of Alphamune groups on d 7; however, intestinal morphology of the
      duodenum was not different between the control and treated birds on d 21. These
      results suggest that feed supplemented with Alphamune can accelerate
      gastrointestinal maturation in turkey poults and is more pronounced in the ileum
      than in other portions of the small intestine.

PMID- 17435028
TI  - Effects of immobilization on the biomechanical properties of the broiler tibia
      and gastrocnemius tendon.
AB  - Researchers have provided much insight into the various factors that influence
      the incidence of musculoskeletal problems in the poultry industry. However, a
      better understanding of the mechanobiology of broiler bone and tendon can have a
      positive effect on the welfare of the production bird and assist in the
      development of improved production practices. This study investigated the
      mechanical adaptability responses due to disuse on the biomechanical properties
      of the broiler tibia and gastrocnemius tendon. Beginning at 3 wk of age, broilers
      were placed in a harness system designed to eliminate load bearing of the leg.
      After 2 wk of this treatment, the average values for body mass and shank length
      of the birds were 58 and 85% of the values for the controls, respectively. The
      treatment reduced the mineral content of the tibia by approximately 50%, tibia
      structural strength by 40%, and tibia material strength by 8%. The structural
      strength and toughness of the gastrocnemius tendon were reduced by 10 and 30%,
      respectively, whereas the material strength, material toughness, and material
      stiffness of the tendon increased by approximately 75, 65, and 70%, respectively.

PMID- 17435029
TI  - Fertilization and blastoderm development of quail oocytes after intracytoplasmic
      injection of chicken sperm bearing the W chromosome.
AB  - Our previous study demonstrated that elongated spermatids and sperm carrying the
      female-specific W-chromosome of the sex-reversed domestic fowl can activate the
      mouse oocyte, but whether they can fertilize the avian oocyte and lead to a
      developing zygote remains undetermined. A single sperm isolated from the semen
      and testis of normal rooster and from a testis of sex-reversed hen was
      microinjected into a quail oocyte and cultured for 20 to 24 h. Blastoderms were
      fixed, cleaved, nuclei stained by 4',6'-diamidino-2-phenylin-dole, and
      developmental stages were assessed. In the normal rooster group, ejaculated and
      testicular sperm induced blastodermal development in 22.6 and 20% of the quail
      oocytes, respectively. The developmental stages ranged from IV to VII. In the sex
      reversal group, 20% of injected testicular sperm induced blastodermal
      development. The blastodermal stages varied from stage III to VI. Blastoderms
      after 4',6'-diamidino-2-phenylindole staining were assayed by PCR to identify the
      W chromosome of either chicken sperm or quail oocyte. The PCR assay results
      showed that 2 out of 9 developed blastoderms microinjected with sperm of sex
      reversed hen were identified containing the female-specific W chromosome derived
      from sex-reversed hen. From these results, it is concluded that chicken sperm
      bearing the W chromosome possess fertilizing ability and can function to
      stimulate blastoderm development similar to that of normal chicken sperm carrying
      the Z chromosome.

PMID- 17435030
TI  - Follicular development and expression of the messenger ribonucleic acid for the
      inhibin/activin subunits in two genetic lines of turkey hens that differ in total
      egg production.
AB  - The characterization of the follicular hierarchy and the expression of the mRNA
      for the inhibin/activin subunits was investigated in the follicles of 2 lines of
      turkey hens selected for over 40 generations for increased egg production (Egg
      line) or increased body weight (Growth line). The follicular hierarchies of 6
      hens from the Egg and Growth lines were characterized in middle (45 wk of age)
      and late production (58 wk of age). Relative follicular weights for individual
      hierarchical follicles (>12 mm), pooled small yellow follicles (5 to 12 mm), and
      large white follicles (2 to 5 mm) were calculated. Total RNA was extracted for
      Northern blot analysis from individual granulosa cell layers of the F1 through F4
      follicles, and from the combined granulosa and theca layers of small yellow
      follicles and large white follicles from an additional 6 hens from each genetic
      line. Egg line hens displayed a more distinct follicular size hierarchy than
      Growth line hens at 45 and 58 wk. Although total follicular weight relative to
      body size was greater at 45 and 58 wk of age for the Egg line hens than the
      Growth line hens, the total number of hierarchical follicles was greater in the
      Growth line hens at 45 and 58 wk of age. Expression of follistatin and the
      inhibin beta(B)-subunit was highest in nonhierarchical follicles, whereas the
      expression of the inhibin alpha- and beta(A)-subunits was highest in the
      hierarchical follicles. The inhibin alpha- and beta(A)-subunit mRNA expression
      pattern in the 4 largest follicles of the Growth line hens was not similar to the
      Egg line hens or characteristic of laying hens that have a high rate of egg
      production. The unusual inhibin subunit mRNA expression in the largest
      hierarchical follicles of the Growth line hens may account for their development
      of an abnormal follicular size hierarchy and for their poor egg production.

PMID- 17435031
TI  - Conjugated linoleic acid and fish oil in laying hen diets: effects on egg fatty
      acids, thiobarbituric acid reactive substances, and tocopherols during storage.
AB  - The effects of incorporating conjugated linoleic acid (CLA) and fish oil in
      laying hen diets on egg CLA, n-3 fatty acid, tocopherol, and TBA reactive
      substances (TBARS) during 60 d of storage were investigated. Hens were fed corn
      soybean meal-based diets containing 3% yellow grease (YG), 2.75% yellow grease +
      0.25% CLA (YG-CLA), 2.5% yellow grease + 0.25% CLA + 0.25% fish oil (YG-CLA-FO),
      or 2.75% yellow grease + 0.25% fish oil (YG-FO). Eggs were collected and stored
      at 4 degrees C up to 60 d. On storage d 0, 20, 40, and 60, eggs (n = 8) from each
      treatment were selected randomly, and tocopherol and TBARS contents were
      measured. Egg total lipid and fatty acids were determined on d 0 and 60 of
      storage. Feeding YG-CLA-FO led to a 5.4 and 7.7% reduction in egg total lipids on
      d 0 and 60 (P < 0.05) when compared with YG eggs. The YG-CLA and YG-CLA-FO diets
      led to a 12% increase in egg saturated fatty acids compared with YG eggs. The
      content of monounsaturated fatty acids were lower ( > 19%) in YG-CLA and YG-CLA
      FO compared with YG. Egg n-3 was highest in YG-FO eggs and lowest in YG eggs (P <
      0.0001). Storage over 60 d led to a 20 and 67% depletion of CLA in the YG-CLA and
      YG-CLA-FO eggs (P < 0.0001). A 29% reduction was observed in the total n-3 fatty
      acid content of YG-CLA-FO eggs at d 60 of storage when compared with d 0 of
      storage (P < 0.0001). Diet and storage increased TBARS (P < 0.0001), which was
      highest in YG-CLA eggs at 60 d of storage. The YG-CLA and YG-CLA-FO diets reduced
      alpha and gamma-tocopherol contents at all days of storage compared with YG eggs
      (P < 0.05). Regardless of diet, egg storage for 40 d or longer depleted egg
      tocopherol contents (P < 0.05). These data demonstrate that healthy eggs with
      increased n-3 fatty acids and CLA can be generated by minor diet modifications,
      but added tocopherol supplementation may be needed to reduce lipid peroxidation
      when n-3 or CLA is included in the hen diet.

PMID- 17435032
TI  - The influence of the season and market class of broiler chickens on breast meat
      quality traits.
AB  - The influence of the season and market class of broiler chickens on breast meat
      quality traits was determined on a total of 18 flocks reared and processed under
      commercial conditions. According to the Italian poultry production system the
      following classes of birds were considered: light size (1.2 kg of carcass weight;
      n = 90) and medium size (1.8 kg of carcass weight; n = 90), represented by
      females slaughtered at 40 and 52 d old, respectively, whereas heavy size were 57
      d-old male broilers (2.4 kg of carcass weight; n = 90). After slaughter, 15
      carcasses per flock (n = 270) were randomly collected during winter (n = 135) and
      summer (n = 135) seasons and used at 24 h postmortem to determine breast
      (pectoralis major) meat color (lightness, redness, and yellowness), pH, drip and
      cook loss, as well as Allo-Kramer (AK) shear values. Furthermore, pectoralis
      minor muscles were used to determine lipid, protein, moisture, and ash content.
      Finally, because the flocks included white- and yellow-skinned broilers, the
      color of the carcass skin was measured to assess the relationship between skin
      and raw breast meat color. With regard to the season, breast meat from birds
      slaughtered during summer exhibited a paler and less red color, lower pH, higher
      drip and cook losses, lower AK-shear, and a higher content of moisture and a
      lower content of protein and ash. In respect to medium and heavy birds, light
      broilers produced breast meat with higher values of redness, lower pH and cook
      loss, higher AK-shear values, and a higher content of moisture and ash. Finally,
      a positive correlation (r = +0.92; P < or = 0.001) between skin and breast meat
      yellowness was found. These results indicate that during summer, broiler breast
      meat undergoes a depression of its functionality and quality. Moreover, the
      market class of birds also determined some differences in breast meat quality
      attributes.

PMID- 17435033
TI  - Germicidal ultraviolet light to lower numbers of Listeria monocytogenes on
      broiler breast fillets.
AB  - Raw broiler breast fillets were subjected to germicidal ultraviolet (UV) light
      (dose of 1,000 microW/cm(2) for 5 min at a wavelength of 254 nm) to evaluate its
      potential to reduce Listeria monocytogenes numbers on raw product before shipment
      to a poultry further-processing plant. Boneless, skinless breast fillets were
      inoculated with 4 different strains of L. monocytogenes 5 min before treatment.
      After the UV treatment, breast fillets were stored at 4 degrees C for 24 h.
      Enumeration of remaining L. monocytogenes was performed using the spread plate
      method on modified Oxford agar. An approximate 2-log reduction in viable L.
      monocytogenes was observed with all 4 strains on UV-treated breast fillets as
      compared with the nontreated breast fillets. The UV treatment caused only slight
      changes in meat color (lightness, redness, and yellowness) on day of treatment or
      after 7 d of storage. This study suggests that UV treatment of raw breast fillets
      at a slaughter plant can significantly reduce L. monocytogenes without negatively
      affecting meat color. This process could be used to reduce the negative effect of
      raw poultry as a transmission vector of L. monocytogenes into a poultry further
      processing plant.

PMID- 17435034
TI  - The use of refused tea as litter material for broiler chickens.
AB  - A completely randomized design experiment was conducted to determine the
      suitability of refused tea (RT) as a litter material for broiler chickens.
      Physiochemical properties of RT were compared with paddy husk (PH). Subsequently,
      broilers were raised on RT- or PH-based litter to compare the performances and
      litter qualities. Twenty-day-old broiler chicks (n = 150) were randomly allocated
      into 6 deep litter pens so that each treatment had 3 replicates. Chicks received
      0.8 ft(2) of floor spacing until d 28 and 1.3 ft(2) thereafter. Each cage had a
      feeder and a drinker. Litter materials and litter samples taken on 28, 35, and 39
      d were analyzed for bulk density, moisture, ash, and N. Chick mortality was low
      (1.3%) and similar on 2 types of litters. Live weights on d 28, 35, 39, and
      weight gains, feed intakes, dressing percentages, and feed conversion ratios were
      not affected by the type of litter material. The bulk density, moisture level,
      and pH of the RT were comparable with PH. Even though the water-holding capacity
      of PH (213%) was significantly higher (P < 0.01) than RT (70%), the latter
      material had significantly higher (P < 0.01) water-releasing capacity compared
      with the former (17.9 vs. 13.6%). Throughout the experiment the RT litter had
      around 10% units higher moisture level than PH litter. By d 39, the moisture
      content of the RT litter was (48%) significantly higher (P = 0.05) than PH litter
      (37%). The N contents of RT litter were higher (P < 0.05) than those of PH on d
      28, 35, and 39, being 8.1, 7.8, and 7% and 3.4, 3.6, and 3%, respectively. It was
      concluded that RT could be successfully used as an alternative litter material
      for broilers. A higher N content in RT-based spent broiler litter would make it
      be a better organic fertilizer and ruminant feed compared with PH-based litter.

PMID- 17435035
TI  - Effect of varying metabolizable energy and crude protein concentrations in diets
      of Pearl Gray guinea fowl pullets. 2. Egg production performance.
AB  - The effect of ME and CP concentrations during the growth phase of Pearl Gray
      guinea fowl pullets on their egg production performance was evaluated. In a 3 x 3
      factorial arrangement, five hundred forty 1-d-old Pearl Gray guinea keets were
      randomly assigned to experimental diets with 2,900, 3,000, and 3,100 kcal of
      ME/kg of diet; each contained 20, 22, and 24% CP, respectively, from 0 to 8 wk of
      age (WOA). From 9 to 16 WOA, experimental diets had 3,000, 3,100, and 3,200 kcal
      of ME/kg of diet, and each contained 17, 19, and 21% CP, respectively. At 17 to
      22, 23 to 27, and 28 to 56 WOA, experimental diets were composed of 3,000, 2,900,
      and 2,800 kcal of ME/kg, and each had 18, 17, and 16% CP, respectively. Dietary
      treatments were replicated 4 times, and feed and water were provided ad libitum.
      Body weights were measured weekly from 0 to 22 WOA, and at 28 to 56 WOA the birds
      were observed for feed consumption, age at first egg, hen-day egg production
      (HDEP), egg weight, egg mass (EM), feed conversion ratio (FCR), internal egg
      quality (IEQ), shell thickness (ST), and BW at the end of each 28-d lay period
      for 7 consecutive periods. Mortality was recorded as it occurred. Overall, BW
      gains were higher (P < 0.05) in birds fed 3,000 and 3,100 Kcal of ME/kg and 24%
      CP from 0 to 8 WOA than other dietary treatments. Percentages HDEP, EM, and IEQ
      were higher (P < 0.05) and FCR was lower (P < 0.05) in pullets fed 3,000 and
      3,100 kcal of ME/kg diet at 0 to 8 WOA than those fed 2,900 kcal of ME/kg. Birds
      on 22 and 24% CP diets at 0 to 8 WOA also exhibited higher HDEP, EM, and lower
      FCR than those on 20% CP diets. Thus, feeding 3,000 to 3,100 kcal of ME/kg of
      diet and 22 to 24% CP at 0 to 8 WOA and 3,100 to 3,200 kcal of ME/kg of diet and
      19 to 21% CP at 9 to 16 WOA improved HDEP, EM, IEQ, and FCR of Pearl Gray guinea
      fowl laying pullets at 28 to 56 WOA.

PMID- 17435037
TI  - An inadequate pulmonary vascular capacity and susceptibility to pulmonary
      arterial hypertension in broilers.
AB  - Broilers are susceptible to pulmonary hypertension syndrome (PHS; ascites
      syndrome) when their pulmonary vascular capacity is anatomically or functionally
      inadequate to accommodate the requisite cardiac output without an excessive
      elevation in pulmonary arterial pressure. The consequences of an inadequate
      pulmonary vascular capacity have been demonstrated experimentally and include
      elevated pulmonary vascular resistance (PVR) attributable to noncompliant, fully
      engorged vascular channels; sustained pulmonary arterial hypertension (PAH);
      systemic hypoxemia and hypercapnia; specific right ventricular hypertrophy, and
      right atrioventricular valve failure (regurgitation), leading to central venous
      hypertension and hepatic cirrhosis. Pulmonary vascular capacity is broadly
      defined to encompass anatomical constraints related to the compliance and
      effective volume of blood vessels, as well as functional limitations related to
      the tone (degree of constriction) maintained by the primary resistance vessels
      (arterioles) within the lungs. Surgical occlusion of 1 pulmonary artery halves
      the anatomical pulmonary vascular capacity, doubles the PVR, triggers PAH,
      eliminates PHS-susceptible broilers, and reveals PHS-resistant survivors whose
      lungs are innately capable of handling sustained increases in pulmonary arterial
      pressure and cardiac output. We currently are using i.v. microparticle injections
      to increase the PVR and trigger PAH sufficient in magnitude to eliminate PHS
      susceptible individuals while allowing PHS-resistant individuals to survive as
      progenitors of robust broiler lines. The microparticles obstruct pulmonary
      arterioles and cause local tissues and responding leukocytes to release
      vasoactive substances, including the vasodilator NO and the highly effective
      vasoconstrictors thromboxane A(2) and serotonin [5-hydroxytryptamine (5-HT)].
      Nitric oxide is the principal vasodilator responsible for modulating
      (attenuating) the PAH response and ensuing mortality triggered by i.v.
      microparticle injections, whereas microparticle-induced increases in PVR can be
      attributed principally to 5-HT. Our observations support the hypothesis that
      susceptibility to PHS is a consequence of anatomically inadequate pulmonary
      vascular capacity combined with the functional predominance of the
      vasoconstrictor 5-HT over the vasodilator NO. The contribution of TxA(2) remains
      to be determined. Selecting broiler lines for resistance to PHS depends upon
      improving both anatomical and functional components of pulmonary vascular
      capacity.

PMID- 17435038
TI  - Pathophysiology of heart failure in broiler chickens: structural, biochemical,
      and molecular characteristics.
AB  - Modern strains of fast-growing meat type poultry are highly susceptible to heart
      failure. Heart-related mortalities are observed predominantly in fast-growing
      broiler chickens, with ascites and sudden death syndrome being the most common
      heart-related conditions in modern broiler flocks. This paper examines the role
      of structural, molecular, and biochemical factors pertinent to the
      pathophysiology of heart failure in fast-growing broilers. Evidence explaining
      the pathogenesis of acute and chronic heart failure, in the context of the
      underlying molecular and biochemical changes in the cardiomyocytes, contractile
      apparatus, and extracellular matrix in the ventricular myocardium are critically
      evaluated and discussed with reference to the clinical signs associated with
      deterioration of heart pump function. The secondary pathophysiological effects on
      the cardiovascular system, resulting from hemodynamic changes associated with the
      failing heart pump, are also reviewed and critically discussed.

PMID- 17435039
TI  - The response of the heart and pulmonary arteries to hypoxia, pressure, and
      volume. A short review.
AB  - The pulmonary arterioles react to hypoxia by contraction and to increased
      pressure and volume by hypertrophy of the muscular wall, referred to as pulmonary
      vascular remodeling, both of which increase vascular resistance and result in
      increased pulmonary arterial pressure. Heart muscle reacts to increased pressure
      by hypertrophy of cardiac myocytes and thickening of the muscular wall. The heart
      responds to increased volume by dilation of the chamber that may result in
      physiologic or pathologic hypertrophy of the muscle wall. Heart muscle cells are
      very sensitive to hypoxia or other insults, and this may result in death of
      individual cardiac myocytes with lengthening and thinning of the remaining heart
      muscle cells and dilation of the chamber in a process called dilated
      cardiomyopathy.

PMID- 17435040
TI  - Metabolic and cardiovascular diseases in poultry: role of dietary lipids.
AB  - In the United States, supplemental dietary lipid is typically provided as an
      animal-vegetable blend using animal tallow or hydrogenated oils from the food
      industry. Lipids from these sources are rich in saturated, trans, n-6 fatty acids
      and poor in n-3 fatty acids. Linoleic (18:2 n-6) and alpha-linolenic (18:3 n-3)
      acids are essential fatty acids and are the precursors of long-chain n-6 and n-3
      fatty acids such as arachidonic and eicosapentaenoic acids (EPA). Ester-linked
      arachidonic acid and EPA can be mobilized by phospholipase A(2) to generate free
      arachidonic acid and EPA, which can act as substrates for cyclooxygenase and
      lipooxygenase to produce eicosanoids. Eicosanoids derived from arachidonic acid,
      prostaglandin E2, thromboxane B2, and leukotriene B4 are proinflammatory and more
      potent than eicosanoids derived from EPA such as prostaglandin E3, thromboxane
      B3, and leukotriene B5. Developing dietary strategies in broiler chickens that
      enhance the n-3 fatty acid content of tissues is also associated with lipid
      oxidation and muscle product quality. Therefore, alternative strategies for
      enhancing tissue n-3 fatty acid content without affecting growth and product
      quality must be devised. The role of maternal (yolk) fatty acids in modulating
      the long-chain n-3 fatty acid content of tissues and eicosanoid production in
      chickens fed a diet lacking in long-chain n-3 fatty acids is investigated. Up to
      d 42 of growth, the cardiac tissues of chicks hatched from hens fed a high n-3
      diet retained higher levels of long-chain n-3 fatty acids than those of chicks
      hatched from hens fed a low n-3 diet. Chicks hatched from hens fed a high n-3
      diet produced less proinflammatory eicosanoids than chicks hatched from hens fed
      a low n-3 diet. Modulating maternal dietary n-3 fatty acids enhances tissue
      retention of n-3 fatty acids during growth and reduces proinflammatory eicosanoid
      production in chicks, which could lead to fewer metabolic and inflammatory
      related disorders in poultry.

PMID- 17435041
TI  - Managing incubation: where are we and why?
AB  - An improvement in the rate of gain of broilers during the past 20 yr has made the
      incubation period a larger percentage of the overall growth period for commercial
      poultry and has played a larger role in improving growth efficiency. Recently,
      hatchery managers have observed concomitant decreases in hatchability and chick
      performance, whereas temperature profiles in the setters and hatchers have not
      changed appreciably. Therefore, these decreases in hatchability, first week
      livability, hatch time, and overall chick quality have precipitated the need for
      a change in the way we manage our hatcheries. Historically, the broiler industry
      within the United States and United Kingdom have successfully utilized multistage
      incubation. Currently, the use of single-stage incubation in Europe has
      increased, because research has shown this system more precisely meets the
      developmental demands of the embryos. Therefore, research has focused on multi-
      and single-stage hatcheries to determine the proper hatch conditions necessary to
      optimize embryonic development, chick quality, and their effects on posthatch
      performance. Studies have shown how increases in shell temperature, independent
      of machine temperature, can result in increases in embryonic mortality, decreased
      heart weight as a percentage of chick weight, decreased yolk-free BW, and
      increased yolk weight. Factors that have contributed to the increase in heat
      stress on developing embryos include egg size, air flow, age of the embryo, and
      breeder flock fertility. Other studies have shown that the variation in chick
      performance can be explained by heat stress in the hatchery. Therefore, symposium
      presentations will show how improvements in our knowledge of the requirements of
      the developing avian embryo can help improve not only hatchability and first week
      livability but posthatch performance.

PMID- 17435042
TI  - Egg storage and the embryo.
AB  - In domestic avian species, eggs are stored at cool temperatures until they can be
      placed into an incubator. The low temperature-induced diapause enables the embryo
      to survive until optimal temperature and humidity incubation conditions can be
      provided to support embryonic growth. Egg storage is a logistical necessity for
      the hatching egg industry both at the breeder farm and at the hatchery. However,
      it is well known that egg storage longer than 7 d negatively influences
      hatchability. At the cellular level, long-term egg storage induces cell death.
      This appears to be occurring both via necrosis and apoptosis. The result is
      higher embryonic mortality and, consequently, lower hatchability. In addition,
      long-term egg storage influences embryonic development and metabolism. Embryos of
      eggs stored long-term can be affected such that they do not initiate growth after
      proper incubation temperatures are provided; they initiate growth, but grow at a
      slower rate than eggs stored short term; and they are affected in both of the
      previously mentioned ways. Development of equipment to measure the embryonic
      metabolism of individually incubating eggs over the entire 21 d of incubation has
      provided further evidence that embryo metabolism has changed due to storage. One
      of the methods to reduce the negative effects of long-term storage has been to
      incubate eggs for short periods before storage. In both turkey and chicken eggs,
      this technique has been successful in improving the hatchability of long-term
      stored eggs. It is hypothesized that particular embryonic developmental stages
      are better able to survive long-term storage. Future research should focus on the
      mechanisms behind this improved ability to survive storage.

PMID- 17435043
TI  - Attainment of thermoregulation as affected by environmental factors.
AB  - The review addresses the development of thermoregulation in poultry embryos as
      well as the effect of acute and chronic changes of environmental factors on this
      process and the incubation temperature being the foremost. In poultry, the early
      development of adaptive body functions, like the thermoregulatory system, is
      characterized by the following peculiarities. First, the development of
      peripheral as well as central nervous thermoregulatory mechanisms start during
      the prenatal ontogeny. However, their maturity is attained during early postnatal
      development. In the perinatal period, environmental factors have a high effect on
      development of temperature regulation. Second, acute changes in the environmental
      conditions induce as a rule first uncoordinated and immediately nonadaptive
      reactions. Later, the uncoordinated nonadaptive reactions change into coordinated
      (adaptive) reactions. Prenatal environmental influences may have a training
      effect on the postnatal efficiency of the thermo-regulatory system. Third,
      functional systems of the organism develop from an open loop system without
      feedback control into a closed system controlled by a feedback mechanism. During
      this critical period, the actual environment modulates the development of the
      respective physiological control systems for the entire life period, especially
      by changes in neuroorganization and expression of related effector genes.
      Knowledge on these mechanisms might be specifically used to generate long-term
      adaptation of the organism to the postnatal climatic conditions (perinatal
      epigenetic temperature adaptation). In poultry, perinatal epigenetic temperature
      adaptation was developed by changes in the incubation temperature. When a
      comparison is made in birds, which were incubated at 37.5 degrees C, a low
      incubation temperature induced postnatal cold adaptation, and warm incubation
      temperature induced postnatal heat adaptation. Perinatal epigenetic temperature
      adaptation exhibited changes in the neuronal thermosensitivity in the
      hypothalamus as well as in the peripheral thermoregulatory mechanisms. These
      alterations could be already found at the end of incubation. Further, temperature
      experienced embryos have a lower c-fos expression than in the control after acute
      heat stress.

PMID- 17435044
TI  - The endocrine interface of environmental and egg factors affecting chick quality.
AB  - Day-old chicks are the endproduct of the hatchery industry and form important
      starting material for the broiler farms. The major objective is to obtain a high
      hatchability of marketable chicks and a low spread of hatch. For the farmers,
      these chicks have to perform well, which is translated in high viability, high
      growth rate, high breast meat yield, and low feed conversion. A good-quality 1-d
      old chick is hence a crucial hinge between the hatchery and the broiler farm.
      Moreover, maximal hatchability is not always synonymous with maximal posthatch
      viability and growth potential of the chick. Quantitative and qualitative scoring
      of chick quality is assessed. We will briefly discuss some recently developed
      scoring systems, which will convert differences in qualitative parameters into a
      quantitative score. Preincubation factors such as egg storage duration and age of
      broiler breeders, as well as incubation conditions, affect day-old chick quality
      and subsequent broiler performance. Heat production and metabolism, hormonal
      balances of thyroid hormones and corticosterone, and gas exchange (O(2), CO(2))
      are of fundamental importance for embryonic development and survival during
      incubation. Results from our studies indicated that embryos with higher pCO(2)
      levels in the air cell and higher triiodothyronine-thyroxine ratios at internal
      pipping or in the newly hatched chicks had higher hatchability, chick quality,
      and posthatch chick growth until 7 d of age. Incubation factors such as
      temperature, turning conditions, or gaseous environment also affect development,
      change concentrations of hormones related to metabolism and growth of the embryo,
      and in this way affect 1-d-old chick quality. Moreover, the spread of the hatch
      process is affected by incubation conditions as well as by the aforementioned
      preincubation factors. Depending on the spread of the hatching curve together
      with the place in the sequence of hatching (early or late) and in interaction
      with quality of the eggs set for incubation, storage duration, and age of
      breeders, there will be a period between hatch and first feeding of variable
      length. This may have repercussions on overall growth and many related
      physiological processes such as yolk uptake, metabolic level, and
      gastrointestinal development. In its turn, time of first feeding is related to
      some crucial hormone levels and enzyme activities for growth that are strongly
      influenced by posthatch food intake such as insulin and p70S6 kinase activity, a
      key enzyme in the control of protein synthesis. The magnitude of the effect of
      delayed feeding is dependent on the spread of hatching as well as on the hatching
      period within the hatching window. This may be related to the different intrinsic
      quality or characteristics of chicks, e.g., early vs. late hatchers, as is shown
      by their respective hormonal levels. The latter may be a causal factor for the
      actual hatching time within the hatching window as well as for the later
      intrinsic quality of the hatched chick, which is not reflected in any of the
      actual scoring systems for chick quality. This is largely ignored in previous
      studies and in hatchery practice so far.

PMID- 17435045
TI  - Nutrition of the developing embryo and hatchling.
AB  - Nutrient needs central to satisfactory egg incubation well-being undergo several
      major changes from fertilization until the reliance of the chick on feed. Glucose
      is central, with the initiation of incubation until the chorioallantois accesses
      O(2) to use for fatty acid oxidation. Nutrient recovery from albumen and yolk is
      largely commensurate with body assembly through to completion of the embryo by 14
      d. Remaining albumen mixes with the amniotic fluid and is orally consumed until
      initiation of emergence. A portion of the albumen is absorbed by the small
      intestine to expand body glycogen reserves. The residual not absorbed contains
      digestive enzyme contributions and enters the yolk sac through its stalk at the
      jejunum and ileum. Interaction of the albumen-amnion digestive enzyme mixture
      with yolk sac contents leads to diverse alterations that influence subsequent use
      of lipids. Rapid removal of very low-density lipoprotein ensues, until pipping
      with triglycerides, expanding body fat depots while cholesterol deposits in the
      liver. A concurrent translocation of Ca from shell mineralizes the skeletal
      system while also crossing yolk sac villi for deposition on phosvitin-based
      granules accruing in its lumen. Loss of chorioallantois with pipping and the
      start of pulmonary respiration predispose a dependence on glycolysis to support
      emergence. Small intestinal villi progressively reorient their enterocytes from
      macromolecule transfer to competence at digestion and absorption after hatching.
      Mobilization of body fat complements contributions from the yolk sac to provide
      fatty acids for generating energy, heat, and water while also combining with
      hepatic cholesterol for membrane expansion and continued development. Calcified
      granules evacuate the yolk sac to further skeletal mineralization in the absence
      of shell contributions. Egg mass, its interior quality, and turning during early
      incubation directly influence the ability of the embryo to access nutrients and
      provide resources to support emergence and the transition of the chick to self
      sufficiency.

PMID- 17435046
TI  - Muscle development in the embryo and hatchling.
AB  - Muscle cell proliferation, migration, adhesion, and fusion are processes involved
      with the formation of multinucleated myotubes that will further differentiate
      into mature muscle fibers. The process of muscle fiber development is nearly
      complete at the time of hatch. Muscle growth during the embryonic period of
      development is characterized by an increase in myoblast cell number through
      hyperplasia. Posthatch muscle fiber growth occurs through muscle fiber
      enlargement by the process of hypertrophy, which results from the recruitment of
      satellite cell nuclei. Hyperplasia and hypertrophy are regulated by factors
      extrinsic to the cell. These extrinsic elements include growth factors and the
      extracellular matrix. The growth factors, hepatocyte growth factor, fibroblast
      growth factor 2, transforming growth factor-beta, insulin-like growth factor, and
      myostatin stimulate or inhibit myoblast and satellite cell proliferation and
      differentiation. Some of these growth factors like fibroblast growth factor 2
      must interact with a low affinity extracellular matrix macromolecule to bind to
      their high affinity receptor necessary for cell signaling. It is probable that
      the expression of extracellular matrix proteins involved in growth factor
      signaling will affect muscle growth properties during hyperplasia and
      hypertrophy. As signaling pathways associated with muscle growth mechanisms are
      further understood, the poultry industry may find it beneficial to include the
      expression of key genes in their selection strategies.

PMID- 17435047
TI  - Abnormal development of urogenital organs in Dlgh1-deficient mice.
AB  - Dlgh1 (discs large homolog 1) is a mammalian homolog of the Drosophila tumor
      suppressor Discs large 1, and is a member of the membrane-associated guanylate
      kinase (MAGUK) scaffolding proteins that contain three PSD-95/Dlg/ZO-1 (PDZ)
      domains. Discs large 1 is involved in epithelial polarization and cell-cell
      adhesion complex formation during Drosophila development. However, the functions
      of Dlgh1 during mammalian development remain to be elucidated. We generated Dlgh1
      knockout mice and found that homozygous Dlgh1-knockout mice developed various
      abnormalities in their renal and urogenital organs. The kidneys and ureters were
      hypoplastic and the lower ends of the ureters were ectopic. In addition, the
      vagina and seminal vesicle, which are derived from the lower part of the
      Mullerian and Wolffian duct, respectively, were absent. Unexpectedly, loss of
      Dlgh1 function in the developing ureters did not disrupt cell-cell junctional
      complexes, but did impair cellular proliferation in the epithelium. These results
      suggest a novel role for Dlgh1 in regulating epithelial duct formation and
      morphogenesis during mammalian development. Although congenital absence of the
      vagina associated with other variable Mullerian duct abnormalities has been
      reported in humans, its mechanism has not yet been clarified. Our findings might
      contribute to a better understanding of such abnormalities.

PMID- 17435048
TI  - Is the urethral smear necessary in asymptomatic men attending a genitourinary
      medicine clinic?

PMID- 17435049
TI  - Screening asymptomatic men for non-specific urethritis.

PMID- 17435050
TI  - Asymptomatic men: should they be tested for urethritis?

PMID- 17435051
TI  - Coma as a presenting symptom of primary HIV infection.
AB  - Primary HIV infection (PHI) is symptomatic in 50-90% of patients. The diagnosis,
      however, is seldom made at first presentation. This is probably because of the
      multifaceted and unspecific manifestations, the omission to perform adequate
      diagnostic testing and the failure to assess risks for PHI. Meningoencephalitis
      has been described as a fairly common presenting condition in PHI, with nuchal
      rigidity, fatigue, photophobia and headache; therefore, PHI should be considered
      in the differential diagnosis of aseptic meningitis. We present the case of a man
      with acute coma and a presumptive diagnosis of viral encephalitis in whom
      serological testing showed HIV encephalitis during PHI.

PMID- 17435052
TI  - GUM modernisation: ratios of follow-up to new patients show sustained decrease.

PMID- 17435053
TI  - HIV, ABC and DHS: age at first sex in Uganda.

PMID- 17435054
TI  - Moving partner notification into the mainstream of routine sexual health care.

PMID- 17435055
TI  - NICE guidance and the National Chlamydia Screening Programme.

PMID- 17435056
TI  - NICE guidance on one-to-one interventions to reduce sexually transmitted
      infections and under-18 conceptions: a view from general practice.

PMID- 17435057
TI  - The National Chlamydia Screening Programme and the NICE guidance on one-to-one
      interventions: remember the under-25s.

PMID- 17435058
TI  - Concomitant meniscal allograft transplantation and autologous chondrocyte
      implantation: minimum 2-year follow-up.
AB  - BACKGROUND: Although recent studies have shown intermediate-term success of both
      meniscal allograft transplantation (MAT) and autologous chondrocyte implantation
      (ACI) performed separately, there have been no peer-reviewed studies focused
      prospectively on the combined procedure. By potentially reestablishing a
      compartment contact area closer to normal, MAT may allow a more optimal
      environment for ACI by reducing stress (stress =force/unit area). On the other
      hand, the literature suggests that MAT alone in the presence of extensive
      chondrosis performs poorly. Restoring the articular cartilage may allow the MAT
      to perform more similarly to series with nearly normal articular cartilage.
      HYPOTHESIS: Performed concomitantly, ACI and MAT will result in significant
      improvements in knee function as measured by functional scoring scales and visual
      analog pain scales. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      Preoperative and postoperative comparisons of Browne modified Cincinnati
      functional levels, Lysholm, visual analog rest and maximum pain, and satisfaction
      scores were recorded. Thirty-six total procedures were performed between 1999 and
      2004. RESULTS: Of the 36 patients entering the series, 29 had >2-year evaluation
      and scores. Four patients were recorded as failures before the 2-year follow-up
      and required revision surgery. Three patients were lost to follow-up. A total of
      21 medial and 8 lateral MAT/femoral condyle ACIs were performed. Sixteen of 29
      patients had concomitant procedures performed, including tibial tuberosity
      osteotomy, anterior cruciate ligament reconstruction, and high tibial osteotomy.
      Patients demonstrated statistically significant improvement in the standardized
      outcome surveys, visual analog pain, and satisfaction scores. The Browne
      Cincinnati (Patient and Clinician, respectively) showed an improvement from 3.9
      (standard deviation [SD], 1.5) and 4.0 (SD, 1.4) preoperatively to 6.3 (SD, 1.9)
      postoperatively for both. The Lysholm also showed an improvement from 57.7 (SD,
      16.2) preoperatively to 77.7 (SD, 19.3) postoperatively. There were no
      significant differences noted in any of the subgroups (medial vs lateral,
      isolated vs concomitant, or unipolar vs bipolar). CONCLUSION: At a minimum of 2
      year follow-up, MAT in combination with ACI demonstrates improvement in both
      symptoms and knee function. However, the improvements are less than literature
      reported outcomes of either procedure performed in isolation.

PMID- 17435059
TI  - A biomechanical comparison of initial fixation strength of 3 different methods of
      anterior cruciate ligament soft tissue graft tibial fixation: resistance to
      monotonic and cyclic loading.
AB  - BACKGROUND: Tibial fixation of soft tissue grafts continues to be problematic in
      the early postoperative period after anterior cruciate ligament reconstruction.
      HYPOTHESIS: No differences exist for resistance to slippage of soft tissue grafts
      fixed with CentraLoc, Intrafix, or 35-mm bioabsorbable interference screws. STUDY
      DESIGN: Controlled laboratory study. METHODS: Bovine tibia and hoof extensor
      tendons were divided into 3 matched groups with 12 tibia and 12 extensor tendons
      in each group. Within each group, 6 specimens underwent monotonic loading to
      failure (1 mm/s), and 6 underwent cyclic loading (10,000 cycles, 125-325 N, 1
      Hz). RESULTS: No statistically significant differences were noted in mean load to
      failure or stiffness. The mean load to failure (and stiffness) for the 3 types of
      fixation were as follows: bioabsorbable interference screw, 631.6 +/- 130.1 N
      (88.17 +/- 6.79 N/mm); Intrafix, 644.3 +/- 195.2 N (81.65 +/- 16.5 N/mm); and
      CentraLoc, 791.1 +/- 72.7 N (77.89 +/- 7.07 N/mm). The slippage rates under
      cyclic loading for the 3 types of fixation were bioabsorbable interference screw,
      0.336 +/- 0.074 microm/cycle; Intrafix, 27.2 +/- 31.6 microm/cycle; and
      CentraLoc, 0.0355 +/- 0.0046 microm/cycle. In this model, CentraLoc proved
      statistically superior in resistance to cyclic loading compared with the
      bioabsorbable interference screw (P < .05) and Intrafix (P < .0001). The
      bioabsorbable interference screw proved statistically superior to Intrafix in
      resistance to cyclic loading (P < .05). CONCLUSIONS: In this bovine model,
      CentraLoc and bioabsorbable interference screws provided superior resistance to
      cyclic loading compared with Intrafix. CLINICAL RELEVANCE: CentraLoc and
      bioabsorbable interference screws showed superior resistance to cyclic loading,
      which may indicate an increased resistance to clinical failure.

PMID- 17435060
TI  - Patellofemoral contact pressures and lateral patellar translation after medial
      patellofemoral ligament reconstruction.
AB  - BACKGROUND: Overtensioning of medial patellofemoral ligament reconstructions may
      lead to adverse surgical outcomes. HYPOTHESIS: Increasing tension on a medial
      patellofemoral ligament graft will increase patellofemoral contact forces and
      decrease lateral patellar translation. STUDY DESIGN: Controlled laboratory study.
      METHODS: Patellofemoral contact pressures were measured in 8 fresh-frozen
      cadaveric knees before and after transection of the medial patellofemoral
      ligament and after a standardized reconstruction surgery. Contact pressures were
      measured at 3 knee angles (30 degrees , 60 degrees , and 90 degrees ) and under 3
      levels of tension applied to the graft (2, 10, and 40 N). For each condition,
      patellar translation was measured at 30 degrees of knee flexion as a 22-N lateral
      force was applied. RESULTS: Graft tension of 2 N restored normal translation, but
      10 N and 40 N significantly restricted motion (5.2 mm and 1.9 mm, respectively).
      Compared with the intact knee, medial patellofemoral contact pressures
      significantly increased (P < .05) when 40 N of tension was applied to the
      reconstruction. Medial contact pressures were restored to normal with 2 N of
      graft tension. Lateral patellar translation was significantly greater (P < .05)
      after the medial patellofemoral ligament was cut (16.3 mm) compared with intact
      (7.7 mm). CONCLUSION: Low (2-N) tension applied to a medial patellofemoral
      ligament reconstruction stabilized the patella and did not increase medial
      patellofemoral contact pressures. Higher loads (10 N and 40 N) progressively
      restricted lateral patellar translation and inappropriately redistributed
      patellofemoral contact pressures. CLINICAL RELEVANCE: Overtensioning can be
      avoided by applying low loads to medial patellofemoral ligament reconstructions,
      which reestablished normal translation and patellofemoral contact pressures.

PMID- 17435061
TI  - Determination of a safe range of knee flexion angles for fixation of the grafts
      in double-bundle anterior cruciate ligament reconstruction: a human cadaveric
      study.
AB  - BACKGROUND: For anterior cruciate ligament reconstruction with a double-bundle
      procedure, one of the major concerns is to not predispose either one of the
      grafts to risk of failure by overloading. HYPOTHESIS: Knee flexion angles between
      15 degrees and 45 degrees for anteromedial graft fixation and 15 degrees for
      posterolateral graft fixation are safe for both grafts in double-bundle anterior
      cruciate ligament reconstruction. STUDY DESIGN: Controlled laboratory study.
      METHODS: Nine human cadaveric knees were tested. The double-bundle anterior
      cruciate ligament reconstruction was conducted with both grafts fixed at 15
      degrees of knee flexion (fixation protocol 15/15) and again with the anteromedial
      and posterolateral grafts fixed at 45 degrees and 15 degrees of knee flexion
      (fixation protocol 45/15). For both fixation protocols, the knee kinematics and
      the in situ forces of the reconstructed anterior cruciate ligament and its
      individual grafts were measured and collected under an anterior tibial load of
      134 N and combined rotatory loads of 10 N.m of valgus and 5 N.m of internal
      tibial torque. The data from both fixation protocols were compared with those of
      an intact knee. RESULTS: In response to the 2 external loading conditions, both
      fixation protocols (15/15 and 45/15) could restore the knee kinematics to within
      2 mm of the intact knee (although statistically significant differences were
      found between fixation protocol 15/15 and the intact knee) and the overall in
      situ forces in the grafts similar to the intact anterior cruciate ligament. In
      response to the 134-N anterior tibial load, the in situ forces in the
      anteromedial graft for both fixation protocols did not exceed those of the intact
      anteromedial bundle. But at 30 degrees and 45 degrees of knee flexion, the in
      situ forces for fixation protocol 15/15 were 20.7% and 22.1% lower, respectively,
      when compared with the intact anteromedial bundle. Under combined rotatory loads,
      the anteromedial graft for fixation protocol 15/15 had in situ forces that were
      45% lower than the intact anteromedial bundle at 30 degrees of knee flexion. The
      in situ force in the posterolateral graft for both fixation protocols did not
      exceed those of the intact posterolateral bundle, nor were they significantly
      different from the intact posterolateral bundle at any of the flexion angles
      tested. CONCLUSION: Both fixation protocols restored knee kinematics without
      predisposing either graft to failure. Therefore, knee flexion angles between 15
      degrees and 45 degrees for graft fixation were found to be safe for the
      anteromedial graft, while 15 degrees of knee flexion was safe for the
      posterolateral graft. CLINICAL RELEVANCE: A range of knee flexion angles that is
      safe for the fixation of both grafts in double-bundle anterior cruciate ligament
      reconstruction was determined.

PMID- 17435062
TI  - Prevention of restenosis: is angioplasty the answer?
AB  - "The drug-coated balloon has the potential to improve the limited results of drug
      eluting stents"

PMID- 17435063
TI  - A case of surgical treatment of severe high blood pressure in an adult.

PMID- 17435064
TI  - Atrial fibrillation--the growing epidemic.

PMID- 17435066
TI  - Optical coherence tomography after cutting balloon angioplasty.

PMID- 17435065
TI  - Alternative treatments for angina.

PMID- 17435067
TI  - Sudden arrhythmic death syndrome.

PMID- 17435068
TI  - Prevention of valve prosthesis--patient mismatch before aortic valve replacement:
      does it matter and is it feasible?

PMID- 17435069
TI  - Real-time three-dimensional echocardiographic diagnosis of postmyocardial
      infarction ventricular septal defect and guidance of transcatheter closure.

PMID- 17435070
TI  - Papillary fibroelastoma in the left ventricular outflow tract.

PMID- 17435071
TI  - Epicardial lipoma mimicking pericardial effusion.

PMID- 17435072
TI  - Triglyceride level is associated with wave reflections and arterial stiffness in
      apparently healthy middle-aged men.
AB  - OBJECTIVE: To investigate the relationship of arterial stiffness and wave
      reflections, which are predictors of cardiovascular risk, with serum triglyceride
      level in healthy adults. DESIGN: Cross-sectional study at the University
      Department of Cardiology. 213 healthy individuals (141 men and 72 premenopausal
      women) not taking any medication and without known cardiovascular disease and
      risk factors, except for smoking. MAIN OUTCOME MEASURES: Central (aortic)
      augmentation index (AIx, a composite measure of arterial stiffness and wave
      reflections), fasting lipid profile (including triglycerides) and 10-year
      Framingham Risk Score (FRS). RESULTS: Compared with women, men had higher serum
      triglyceride level (median (interquartile range) (89 (67-117) vs 73 (54-96)
      mg/dl, p<0.01) and lower AIx (17.7 (1.0) vs 26.3 (1.4), p<0.001). In both
      genders, serum triglyceride levels were significantly associated with FRS (men: r
      = 0.43, p<0.001; women: r = 0.37, p<0.01) and AIx (men: r = 0.21, p<0.05; women:
      r = 0.26, p<0.05). In men, multivariate linear regression analysis showed an
      association between triglyceride level and AIx (standardised beta coefficient =
      0.19, p = 0.009), independent of age, blood pressure, heart rate, height, weight,
      smoking habits, total cholesterol and HDL-cholesterol levels. On the other hand,
      in women, the unadjusted correlation between triglyceride level and AIx was
      largely explained when the above mentioned confounders were taken into account
      (beta = -0.016, p = 0.86). CONCLUSION: In healthy men, serum triglyceride levels
      are associated with indices of arterial stiffness and wave reflections, which are
      important determinants of cardiovascular function and risk. The role of
      triglycerides in the vascular function of women warrants further investigation.

PMID- 17435073
TI  - Management of end stage heart failure.

PMID- 17435074
TI  - Rescue percutaneous coronary intervention: does the concept make sense?

PMID- 17435075
TI  - New percutaneous treatments for valve disease.

PMID- 17435076
TI  - Ventricular non-compaction in the setting of double-outlet right ventricle
      (tetralogy of Fallot type) with doubly committed subarterial ventricular septal
      defect.

PMID- 17435077
TI  - Respiratory syncytial virus induces insensitivity to beta-adrenergic agonists in
      mouse lung epithelium in vivo.
AB  - Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in
      infants and children worldwide. We wished to determine whether intratracheal
      administration of beta-agonists improved alveolar fluid clearance (AFC) across
      the distal respiratory epithelium of RSV-infected mice. Following intranasal
      infection with RSV strain A2, AFC was measured in anesthetized, ventilated BALB/c
      mice by instillation of 5% BSA into the dependent lung. We found that direct
      activation of protein kinase A by forskolin or 8-bromo-cAMP increased AFC at day
      2 after infection with RSV. In contrast, short- and long-acting beta-agonists had
      no effect at either day 2 or day 4. Insensitivity to beta-agonists was not a
      result of elevated plasma catecholamines or lung epithelial cell beta-adrenergic
      receptor degradation. Instead, RSV-infected mice had significantly higher levels
      of phosphorylated PKCzeta in the membrane fractions of their lung epithelial
      cells. In addition, insensitivity to beta-agonists was mediated in a paracrine
      fashion by KC (the murine homolog of CXCL8) and reversed by inhibition of either
      PKCzeta or G protein-coupled receptor kinase 2 (GRK2). These results indicate
      that insufficient response to beta-agonists in RSV may be caused, at least in
      part, by impaired beta-adrenergic receptor signaling, as a consequence of GRK2
      mediated uncoupling of beta-adrenergic receptors from adenylyl cyclase.

PMID- 17435078
TI  - A paradoxical temporal response of the PTHrP/PPARgamma signaling pathway to
      lipopolysaccharide in an in vitro model of the developing rat lung.
AB  - Chorioamnionitis alters lung development, resulting in a paradoxical decrease in
      the incidence of respiratory distress syndrome but an increase in the incidence
      of bronchopulmonary dysplasia (BPD). The mechanism(s) underlying this disparity
      in the pulmonary outcomes is not known. We hypothesized that specific alterations
      in alveolar epithelial-mesenchymal interactions might explain this apparent
      disparity in the pulmonary outcome following chorioamnionitis. We determined the
      effects of lipopolysaccharide (LPS) on parathyroid hormone-related protein
      (PTHrP)-driven epithelial-mesenchymal interactions that are essential for normal
      lung development and homeostasis. Lung explants from embryonic day 19.5 Sprague
      Dawley rat fetuses were treated with LPS with or without a PTHrP pathway agonist,
      prostaglandin J(2) (PGJ(2)). LPS treatment affected the production of
      proinflammatory cytokines and the expression of the key markers of the epithelial
      mesenchymal paracrine interactions in a time-dependent manner. At 6 h, there was
      a significant increase in the expression of PTHrP and the other key markers of
      alveolar homeostasis without any significant effect on alpha-smooth muscle actin
      (alphaSMA). In contrast, at 72 h, there was a significant decrease in the
      expression of PTHrP and the other key markers of alveolar homeostasis accompanied
      by a significant increase in alphaSMA expression. The cytokine and molecular
      changes at 72 h were completely prevented by the concomitant treatment with
      PGJ(2). We speculate that these data provide a likely mechanism for the acute
      stimulation of lung differentiation, accompanied paradoxically by BPD following
      chorioamnionitis, and suggest that by specifically targeting PTHrP signaling, the
      inflammation-induced molecular injury that is known to result in BPD can be
      prevented.

PMID- 17435079
TI  - Differential roles of p55 and p75 tumor necrosis factor receptors on stretch
      induced pulmonary edema in mice.
AB  - Ventilator-induced lung injury plays a crucial role in the outcome of patients
      with acute lung injury. Previous studies have shown a role for the cytokine tumor
      necrosis factor-alpha (TNF) in stretch-induced alveolar neutrophil recruitment,
      but the involvement of TNF in stretch-induced pulmonary edema is unclear. We
      investigated the effects of TNF through its individual p55 and p75 receptors on
      early pulmonary edema formation during high stretch ventilation, before
      neutrophil infiltration. Anesthetized wild-type or TNF receptor single/double
      knockout mice were ventilated with high tidal volume ( approximately 38 ml/kg)
      for 2 h or until they developed arterial hypotension. Pulmonary edema was
      assessed by physiological parameters including respiratory mechanics and blood
      gases, and by lavage fluid protein, lung wet:dry weight ratio, and lung
      permeability measurements using fluorescence-labeled albumin. High stretch
      ventilation in wild-type and TNF receptor double knockout animals induced similar
      pulmonary edema, and only 25-30% of mice completed the protocol. In contrast, the
      p55 receptor knockout mice were strongly protected from edema formation, with all
      animals completing the protocol. Myeloperoxidase assay indicated that this
      protective effect was not associated with decreased pulmonary neutrophil
      sequestration. The p75 receptor knockout mice, however, displayed increased
      susceptibility to edema formation, and no animals survived the full 2 h. These
      results demonstrate a novel role for TNF signaling (independent from its effects
      on neutrophil recruitment) specifically through the p55 receptor, in promoting
      high stretch-induced pulmonary edema, whereas p75 signaling may play an opposing
      role.

PMID- 17435080
TI  - Immunotargeting of catalase to lung endothelium via anti-angiotensin-converting
      enzyme antibodies attenuates ischemia-reperfusion injury of the lung in vivo.
AB  - Limitation of reactive oxygen species-mediated ischemia-reperfusion (I/R) injury
      of the lung by vascular immunotargeting of antioxidative enzymes has the
      potential to become a promising modality for extension of the viability of banked
      transplantation tissue. The preferential expression of angiotensin-converting
      enzyme (ACE) in pulmonary capillaries makes it an ideal target for therapy
      directed toward the pulmonary endothelium. Conjugates of ACE monoclonal antibody
      (MAb) 9B9 with catalase (9B9-CAT) have been evaluated in vivo for limitation of
      lung I/R injury in rats. Ischemia of the right lung was induced for 60 min
      followed by 120 min of reperfusion. Sham-operated animals (sham, n = 6) were
      compared with ischemia-reperfused untreated animals (I/R, n = 6), I/R animals
      treated with biotinylated catalase (CAT, n = 6), and I/R rats treated with the
      conjugates (9B9-CAT, n = 6). The 9B9-CAT accumulation in the pulmonary
      endothelium of injured lungs was elucidated immunohistochemically. Arterial
      oxygenation during reperfusion was significantly higher in 9B9-CAT (221 +/- 36
      mmHg) and sham (215 +/- 16 mmHg; P < 0.001 for both) compared with I/R (110 +/-
      10 mmHg) and CAT (114 +/- 30 mmHg). Wet-dry weight ratio of I/R (6.78 +/- 0.94%)
      and CAT (6.54 +/- 0.87%) was significantly higher than of sham (4.85 +/- 0.29%; P
      < 0.05), which did not differ from 9B9-CAT (5.58 +/- 0.80%). The significantly
      lower degree of lung injury in 9B9-CAT-treated animals compared with I/R rats was
      also shown by decreased serum levels of endothelin-1 (sham, 18 +/- 9 fmol/mg;
      I/R, 42 +/- 12 fmol/mg; CAT, 36 +/- 11 fmol/mg; 9B9-CAT, 26 +/- 9 fmol/mg; P <
      0.01) and mRNA for inducible nitric oxide synthase (iNOS) [iNOS-GAPDH ratio:
      sham, 0.15 +/- 0.06 arbitrary units (a.u.); I/R, 0.33 +/- 0.08 a.u.; CAT, 0.26 +/
      0.05 a.u.; 9B9-CAT, 0.14 +/- 0.04 a.u.; P < 0.001]. These results validate
      immunotargeting by anti-ACE conjugates as a prospective and specific strategy to
      augment antioxidative defenses of the pulmonary endothelium in vivo.

PMID- 17435081
TI  - Drug safety reform at the FDA--pendulum swing or systematic improvement?

PMID- 17435082
TI  - PDUFA reauthorization--drug safety's golden moment of opportunity?

PMID- 17435083
TI  - Paying for drug approvals--who's using whom?

PMID- 17435095
TI  - Survey of flea infestation in dogs and cats in the United Kingdom during 2005.
AB  - During 2005, 31 uk veterinary practices participated in a survey of flea
      infestation, during which 2653 dogs and 1508 cats were examined for evidence of
      flea infestation and skin disease compatible with flea allergy dermatitis (fad).
      The prevalence of flea infestation in the cats was 21.09 per cent, significantly
      (P<0.001) higher than in the dogs (6.82 per cent). The prevalence of skin lesions
      compatible with fad in the cats (8.02 per cent) was also significantly (P<0.001)
      higher than in the dogs (3.32 per cent). Flea infestations were more common in
      households with cats and with more than one pet. Of 467 fleas identified from the
      cats, 462 (98.93 per cent) were Ctenocephalides felis, one was Ctenocephalides
      canis, one was Archaeopsylla erinacei, two were Pulex irritans, and one was
      Spilopsyllus cuniculi. Of 336 fleas identified from the dogs, 313 (93.15 per
      cent) were C felis, five were C Canis, 12 were A erinacei, five were P irritans,
      and one was Ceratophyllus (Nosophyllus) fasciatus. Almost half of the owners of
      the dogs and cats were unaware of their pet's flea infestation. The overall
      prevalence of fleas and/or skin lesions that could potentially be compatible with
      fad was 7.46 per cent in the dogs and 22.28 per cent in the cats.

PMID- 17435085
TI  - Characterization of the VIER F-BOX PROTEINE genes from Arabidopsis reveals their
      importance for plant growth and development.
AB  - E3 ubiquitin ligases (E3s) target proteins for degradation by the 26S proteasome.
      In SKP1/CDC53/F-box protein-type E3s, substrate specificity is conferred by the
      interchangeable F-box protein subunit. The vast majority of the 694 F-box
      proteins encoded by the Arabidopsis thaliana genome remain to be understood. We
      characterize the VIER F-BOX PROTEINE (VFB; German for FOUR F-BOX PROTEINS) genes
      from Arabidopsis that belong to subfamily C of the Arabidopsis F-box protein
      superfamily. This subfamily also includes the F-box proteins TRANSPORT INHIBITOR
      RESPONSE1 (TIR1)/AUXIN SIGNALING F-BOX (AFB) proteins and EIN3 BINDING F-BOX
      proteins, which regulate auxin and ethylene responses, respectively. We show that
      loss of VFB function causes delayed plant growth and reduced lateral root
      formation. We find that the expression of a number of auxin-responsive genes and
      the activity of DR5:beta-glucuronidase, a reporter for auxin response, are
      reduced in the vfb mutants. This finding correlates with an increase in the
      abundance of an AUXIN/INDOLE-3-ACETIC ACID repressor. However, we also find that
      auxin responses are not affected in the vfb mutants and that a representative VFB
      family member, VFB2, cannot functionally complement the tir1-1 mutant. We
      therefore exclude the possibility that VFBs are functional orthologs of TIR1/AFB
      proteins.

PMID- 17435096
TI  - Retrospective evaluation of the long-term outcome of non-surgical management of
      74 dogs with clinical hip dysplasia.
AB  - The long-term outcome for dogs treated non-surgically for clinical signs of
      canine hip dysplasia were evaluated retrospectively; 74 dogs were evaluated by a
      postal questionnaire sent to their owners, and 24 of these were also evaluated by
      a veterinary clinical examination. A total of 11 outcome variables were
      evaluated. Depending on the variable assessed, between 31 (41.9 per cent) and 49
      (66.2 per cent) of the dogs remained clinically affected according to their
      owner's assessment, and between 17 (70.8 per cent) and 23 (95.8 per cent) of the
      24 dogs had abnormalities attributed to hip osteoarthritis according to the
      veterinary assessment. Orthopaedic abnormalities other than hip dysplasia
      affected 17 of the 24 dogs. Long-term medications had been prescribed for the
      treatment of clinical signs associated with hip dysplasia in 41 of the 74 dogs.

PMID- 17435084
TI  - The nuclear-encoded factor HCF173 is involved in the initiation of translation of
      the psbA mRNA in Arabidopsis thaliana.
AB  - To gain insight into the biogenesis of photosystem II (PSII) and to identify
      auxiliary factors required for this process, we characterized the mutant hcf173
      of Arabidopsis thaliana. The mutant shows a high chlorophyll fluorescence
      phenotype (hcf) and is severely affected in the accumulation of PSII subunits. In
      vivo labeling experiments revealed a drastically decreased synthesis of the
      reaction center protein D1. Polysome association experiments suggest that this is
      primarily caused by reduced translation initiation of the corresponding psbA
      mRNA. Comparison of mRNA steady state levels indicated that the psbA mRNA is
      significantly reduced in hcf173. Furthermore, the determination of the psbA mRNA
      half-life revealed an impaired RNA stability. The HCF173 gene was identified by
      map-based cloning, and its identity was confirmed by complementation of the hcf
      phenotype. HCF173 encodes a protein with weak similarities to the superfamily of
      the short-chain dehydrogenases/reductases. The protein HCF173 is localized in the
      chloroplast, where it is mainly associated with the membrane system and is part
      of a higher molecular weight complex. Affinity chromatography of an HCF173 fusion
      protein uncovered the psbA mRNA as a component of this complex.

PMID- 17435097
TI  - Kinetic evaluation of normal walking and jumping in cats, using a pressure
      sensitive walkway.
AB  - The kinetic parameters of the limbs of 23 normal, client-owned cats were
      evaluated by encouraging them to walk and jump normally on a pressure-sensitive
      walkway. Each cat was encouraged to walk across the walkway five times over a
      period of 30 to 45 minutes (by using food, toys, the owner's presence and a
      purpose-built tunnel) at a target speed of 0.6 m/s (and an acceleration of less
      than +/- 0.1 m/s(2)). They were then encouraged to jump on to the walkway from a
      height of 1 m five times at five-minute intervals. The kinetic parameters of peak
      vertical force (PVF) and vertical impulse (VI) were measured for each limb (the
      forelimbs only for the jumps), and expressed as a percentage of bodyweight
      (PVF(%BW) and VI(%BW/S)). Fifteen of the 23 cats satisfactorily completed three
      to five walks and two to five jumps that could be analysed. There were no
      significant differences between the PVF or VI of the left and right limbs, but
      both parameters were significantly greater for the forelimbs than the hindlimbs
      (P<0.001) for the walking data. The mean (sd) PVF(%BW) for the forelimbs and
      hindlimbs were 48.2 (6.0) and 38.3 (4.0), respectively, and the mean VI(%BW/s)
      were 16.9 (3.2) and 13.3 (2.8). Jumping down generated significantly greater PVF
      (P<0.01) and slightly greater VI than during walking; there were no significant
      differences between the left and right forelimbs. The mean PVF(%BW) was 148.9
      (16.4) and the mean VI(%BW/s) was 18.1 (4.3).

PMID- 17435098
TI  - Behaviour and personality of pet rabbits and their interactions with their
      owners.
AB  - The behaviour and personality of 102 pet rabbits and their interactions with
      their owners were assessed in their home environment. Information was obtained by
      interviews with the owner and by direct observation, and the owners were asked to
      describe the personality of their rabbit. A 10-minute assessment of the rabbit's
      behaviour in its normal environment was then carried out. Owners who were
      confident in handling their rabbit handled them more frequently and rabbits that
      were handled more frequently struggled less when they were being handled. Rabbits
      observed with a companion spent the largest proportion of their time engaged in
      social behaviour, and rabbits observed out of a hutch spent significantly more
      time grazing, hopping and playing. Owners used a wide range of adjectives to
      describe their rabbits' personalities with the most common term being ;friendly'.

PMID- 17435099
TI  - Treatment of canine atopic dermatitis with azathioprine: a pilot study.

PMID- 17435100
TI  - Cowpox virus pneumonia in a domestic cat in Great Britain.

PMID- 17435101
TI  - Progesterone insufficiency in bitches in early and late dioestrus.

PMID- 17435102
TI  - Systemic mycobacteriosis in an inland bearded dragon (Pogona vitticeps).

PMID- 17435103
TI  - Efficacy of imidacloprid 10 per cent/moxidectin 2-5 per cent spot-on in the
      treatment of cheyletiellosis in dogs.

PMID- 17435104
TI  - Bacteraemia and antimicrobial susceptibility in dogs.

PMID- 17435105
TI  - Attitudes to badger culling.

PMID- 17435106
TI  - Louping ill in horses.

PMID- 17435107
TI  - Conditional deletion of cytochrome P450 oxidoreductase in the liver and
      gastrointestinal tract: a new model for studying the functions of the P450
      system.
AB  - We have previously described a mouse model, where hepatic cytochrome P450
      oxidoreductase (POR) expression has been deleted, resulting in almost complete
      ablation of hepatic P450 function [Hepatic P450 Reductase Null (HRN)]. HRN mice
      grow normally but develop fatty livers, and they have increased cytochrome P450
      levels. Associated with the hepatic lipid accumulation are significant changes in
      the expression of genes controlling lipid homeostasis. We have characterized this
      model extensively and demonstrated its value in drug efficiency testing, in
      toxicokinetics, and in evaluating the role of the hepatic P450 system in drug
      pharmacokinetics. To extend the deletion of POR, and P450 inactivation, to other
      tissues, and to develop the utility of this model, we have generated a mouse
      where POR can be deleted conditionally in the liver and gastrointestinal tract
      using the rat cytochrome P450 CYP1A1 promoter to drive Cre recombinase
      expression. Administration of the CYP1A1 inducers tetrachlorodibenzo-p-dioxin or
      beta-naphthoflavone resulted in both hepatic and gastrointestinal deletion of
      POR, whereas administration of 3-methylcholanthrene resulted specifically in loss
      of hepatic POR expression. In all cases, the resulting hepatic phenotype seemed
      identical to that of the HRN model, including increased cytochrome P450
      expression. Hepatic deletion of POR and the subsequent increase in P450
      expression were dependent on inducer dose, with maximal POR deletion occurring at
      a single dose of 3-methylcholanthrene of 40 mg/kg. This model provides a powerful
      approach for studying the functions of POR as well as in the evaluation of the
      role of hepatic and gastrointestinal P450s in drug deposition and chemical
      toxicity.

PMID- 17435108
TI  - Role of transforming growth factor beta in rat bladder smooth muscle cell
      proliferation.
AB  - Conditions associated with hypertrophy of the urinary bladder have repeatedly
      been associated with an increased urinary excretion of transforming growth factor
      (TGF) beta in both rats and patients. Because TGFbeta can have both growth
      promoting and -inhibiting effects, we have studied its effects on cell growth and
      death in primary cultures of rat bladder smooth muscle cells. TGFbeta1, TGFbeta2,
      or TGFbeta3 did not cause apoptosis, but all three isoforms inhibited DNA
      synthesis with similar potency (EC(50) of approximately 0.1 ng/ml) and efficacy.
      Such inhibition was antagonized by a specific TGFbeta receptor antagonist and
      independent of the presence of serum. Mitogen-activated protein kinases (MAPKs)
      are involved in the control of cell growth, and all three TGFbeta isoforms
      inhibited activation of the extracellular signal-regulated kinase, c-Jun NH(2)
      terminal kinase, and p38 MAPK subfamilies. Nevertheless, the inhibitory effects
      of the TGFbeta isoforms on DNA synthesis were not affected by presence of
      inhibitors of the three MAPK pathways. TGFbeta did not alter cell size as
      measured by flow cytometry or mitochondrial activity, an integrated measure of
      cell size and number. We conclude that our data do not support the hypothesis
      that TGFbeta is a mediator of rat bladder hypertrophy.

PMID- 17435109
TI  - An in vitro study with an ussing chamber showing that unfractionated heparin
      crosses rat gastric mucosa.
AB  - Heparin, traditionally given parenterally, is used to treat and prevent
      thrombosis. Our previous results suggest that orally administered unfractionated
      heparin (UFH) is absorbed and has antithrombotic effects. However, there is
      little evidence indicating the site and mechanism of heparin absorption. Our aim
      was to determine whether the stomach is an absorption site. Rat gastric mucosa
      was mounted in an Ussing chamber, and UFH was added to the mucosal buffer at pH
      7.4. Potential difference (PD), resistance (R), and short circuit current (I(sc))
      across the mucosa were determined comparing the mucosal to the serosal side.
      Mucosal and serosal buffers and tissue were analyzed for chemical heparin and
      anticoagulant activity, antifactor Xa (anti-Xa) and antifactor IIa (anti-IIa)
      activity. The PD became more negative on UFH addition. Following a lag period, PD
      returned to the resting level. Changes in R followed those in PD, whereas I(sc)
      did not change. Heparin was found in the serosal and mucosal buffer and tissue.
      Heparin in the serosal buffer had anti-Xa and anti-IIa activity. Decreasing the
      pH of the mucosal buffer to 4.0, decreased the lag period for PD. Decreasing the
      concentration of UFH resulted in less pronounced changes in PD and less heparin
      in the serosal buffer. Changes in PD suggest that heparin moves across the
      mucosa. Presence of heparin in the serosal buffer and mucosal tissue, indicate
      that heparin crosses rat gastric mucosa. A stable I(sc) indicates passive
      diffusion contributes to heparin movement. The stomach could be a site for oral
      heparin absorption.

PMID- 17435110
TI  - Solar UV forecasts: a randomized trial assessing their impact on adults' sun
      protection behavior.
AB  - This study examined the effectiveness of solar UV forecasts and supporting
      communications in assisting adults to protect themselves from excessive weekend
      sun exposure. The study was conducted in Australia, where 557 adult participants
      with workplace e-mail and Internet access were randomly allocated to one of three
      weather forecast conditions: standard forecast (no UV), standard forecast + UV,
      standard forecast + UV + sun-protection messages. From late spring through summer
      and early autumn, they were e-mailed weekend weather forecasts late in the
      working week. Each Monday they were e-mailed a prompt to complete a Web-based
      questionnaire to report sun-related behavior and any sunburn experienced during
      the previous weekend. There were no significant differences between weather
      forecast conditions in reported hat use, sunscreen use, sun avoidance, or
      sunburn. Results indicate that provision of solar-UV forecasts in weather
      forecasts did not promote markedly enhanced personal sun-protection practices
      among the adults surveyed.

PMID- 17435111
TI  - Beauty salons: a promising health promotion setting for reaching and promoting
      health among African American women.
AB  - African American women suffer disproportionately from a wide range of health
      disparities. This article clarifies how beauty salons can be mobilized at all
      levels of the social-ecological framework to address disparities in health among
      African American women. The North Carolina BEAUTY and Health Project is a
      randomized, controlled intervention trial that takes into account the unique and
      multilevel features of the beauty salon setting with interventions that address
      owners, customers, stylists; interactions between customers and stylists; and the
      salon environment. The authors make explicit the role of the political economy of
      health theoretical perspective for understanding important factors (social,
      political, historical, and economic) that should be considered if the goal is to
      create successful, beauty-salon-based interventions. Despite some important
      challenges, the authors contend that beauty salons represent a promising setting
      for maximizing reach, reinforcement, and the impact of public health
      interventions aimed at addressing health disparities among African American
      women.

PMID- 17435112
TI  - Reversal of autoimmune disease in lupus-prone New Zealand black/New Zealand white
      mice by nonmyeloablative transplantation of purified allogeneic hematopoietic
      stem cells.
AB  - Patients with severe systemic lupus erythematosus (SLE) refractory to
      conventional treatment are candidates for autologous hematopoietic stem cell
      (HSC) transplantation if the intent is to reset the immunologic clock. These
      patients might be candidates for allotransplantation with (SLE)-resistant major
      histocompatibility complex (MHC) haplotype-matched HSC if partial or complete
      replacement of an autoimmune-prone system is the intent. Using lupus-prone New
      Zealand black x New Zealand white (NZBW) mice, we investigated the use of highly
      enriched, haplomismatched, allogeneic HSC to prevent development of or to treat
      established autoimmune pathology. Young NZBW mice receiving purified allogeneic
      HSC transplants had improved survival, decreased proteinuria, circulating immune
      complexes, and autoantibodies to nuclear antigens than did untreated mice or mice
      given NZBW HSCs. NZBW mice with established lupus-like disease that received
      nonmyeloablative conditioning and transplants of (MHC) haplomismatched allogeneic
      HSCs also had greatly increased overall survival. Mice that received transplants
      exhibited stabilization or reversal of their lupus symptoms; stabilized or
      decreased proteinuria, and a lower frequency of elevated circulating immune
      complexes or autoantibodies than did control mice. Induction of durable mixed
      chimerism by transplantation of purified allogeneic HSCs after nonmyeloablative
      conditioning has the potential to reverse symptoms of established NZBW lupus.

PMID- 17435113
TI  - Functional analysis of fibrin {gamma}-chain cross-linking by activated factor
      XIII: determination of a cross-linking pattern that maximizes clot stiffness.
AB  - Activated coagulation factor XIII (FXIIIa) cross-links the gamma-chains of fibrin
      early in clot formation. Cross-linking of the alpha-chains occurs more slowly,
      leading to high molecular weight multimer formations that can also contain gamma
      chains. To study the contribution of FXIIIa-induced gamma-chain cross-linking on
      fibrin structure and function, we created 2 recombinant fibrinogens
      (gammaQ398N/Q399N/K406R and gammaK406R) that modify the gamma-chain cross-linking
      process. In gammaK406R, gamma-dimer cross-links were absent, but FXIIIa produced
      a cross-linking pattern similar to that observed in tissue transglutaminase cross
      linked fibrin(ogen) with mainly alpha-gamma cross-links. In Q398N/Q399N/K406R,
      cross-links with any gamma-chain involvement were completely absent, and only
      alpha-chain cross-linking occurred. Upon cross-linking, recombinant normal fibrin
      yielded a 3.5-fold increase in stiffness, compared with a 2.5-fold increase by
      alpha-chain cross-linking alone (gammaQ398N/Q399N/K406R). gammaK406R fibrin
      showed a 1.5-fold increase in stiffness after cross-linking. No major differences
      in clot morphology, polymerization, and lysis rates were observed, although fiber
      diameter was slightly lower in cross-linked normal fibrin relative to the
      variants. Our results show that gamma-chain cross-linking contributes
      significantly to clot stiffness, in particular through gamma-dimer formation;
      alpha-gamma hybrid cross-links had the smallest impact on clot stiffness.

PMID- 17435114
TI  - Quantitation of hepcidin from human and mouse serum using liquid chromatography
      tandem mass spectrometry.
AB  - The hepatic peptide hormone hepcidin is considered the central regulator of iron
      metabolism. Characterizing the circulating levels of this peptide is critical to
      understanding its role in the development of clinically relevant syndromes, such
      as anemia of inflammation/chronic disease, and may provide insight into potential
      clinical interventions. While quantitative methods have been published for the
      determination of urinary hepcidin and serum prohepcidin, no definitive methods
      have been published for the determination of hepcidin in serum. In this report,
      we describe a quantitative method for the determination of both human and mouse
      hepcidin in serum and plasma. The method employs protein precipitation and solid
      phase extraction followed by liquid chromatographic separation and tandem mass
      spectrometry detection. The method has a quantitative range of 0.25 ng/mL to 500
      ng/mL serum for mouse hepcidin and 1 ng/mL to 500 ng/mL serum for human hepcidin.
      The method uses small sample volumes (50 microL for mice and 100 microL for
      humans) and 96-well formats for rapid sample processing. The method was used to
      establish baseline serum and plasma concentrations of hepcidin in normal C57Bl/6
      mice and healthy human volunteers.

PMID- 17435116
TI  - Coccidioidomycosis in the U.S. Military: a review.
AB  - Coccidioidomycosis has had an impact on the military since the discovery of the
      causative agent, Coccidioides immitis, over a century ago. The first reports of
      Coccidioides outbreaks affecting U.S. military personnel were reported by Smith
      and others during World War II. Since that time, numerous outbreaks and sporadic
      cases have occurred, affecting both the health and readiness of our armed forces.
      This article summarizes the impact of Coccidioides sp. on our military troops
      with a review of the literature, a description of the experience at a tertiary
      referral hospital treating the disease, and a synopsis of incidence studies
      conducted at bases in the southwestern United States. The substantial effect that
      coccidioidomycosis has had on the military supports the development of both newer
      and more effective treatments as well as a Valley Fever vaccine for prevention of
      this disease.

PMID- 17435115
TI  - X-linked clonality testing: interpretation and limitations.
AB  - Clonality often defines the diseased state in hematology. Clonal cells are
      genetically homogenous and derived from the same precursor; their detection is
      based on genotype or phenotype. Genotypic clonality relies on somatic mutations
      to mark the clonal population. Phenotypic clonality identifies the clonal
      population by the expression pattern of surrogate genes that track the clonal
      process. The most commonly used phenotypic clonality methods are based on the X
      chromosome inactivation principle. Clonality detection based on X-chromosome
      inactivation patterns (XCIP) requires discrimination of the active from the
      inactive X chromosome and differentiation of each X chromosome's parental origin.
      Detection methods are based on detection of X-chromosome sequence polymorphisms
      identified by protein isoforms, transcribed mRNA, and methylation status. Errors
      in interpreting clonality tests arise from stochastic, genetic, and cell
      selection pressures on the mechanism of X inactivation. Progressive X-chromosome
      skewing has recently been suggested by XCIP clonality studies in aging
      hematopoietic cells. This has led to new insights into the pathophysiology of X
      linked and autoimmune disorders. Other research applications include combining
      XCIP clonality testing with genetic clonality testing to identify clonal
      populations with yet-to-be-discovered genetic changes.

PMID- 17435117
TI  - Type II secretion and type IV pili of Francisella.
AB  - Francisella tularensis genomes encode homologues of type IV pili. Though several
      F. tularensis genes required for Tfp expression are homologous to genes required
      for type II secretion (T2S), these gene clusters mainly bear structural
      signatures that are typical of Tfp. There is preliminary evidence that different
      F. tularensis subspecies express Tfp-like surface structures, but there are also
      some interesting differences between the subspecies. One difference between the
      nonpathogenic subspecies novicida (F. novicida) and the highly pathogenic type A
      strains is in sequence of one of the predicted pilin genes, pilA. In contrast,
      type B strains show several differences compared to type A strains, two predicted
      pilin genes and the pilT gene are pseudogenes, while pilA is identical to pilA
      that is encoded by the type A strains. This is likely significant as PilA
      contributes to virulence of type B strains while PilT is essential for Tfp
      retraction in other bacterial pathogens. Tfp-mediated protein secretion is only
      evident in in vitro grown F. novicida. Surprisingly, secretion of several F.
      novicida proteins was dependent on pilA and other genes with postulated roles in
      Tfp expression. F. novicida secretion mutants were more virulent in the mouse
      infection model. Thus, in F. novicida, Tfp gene clusters serve both T2S and Tfp
      assembly and it is tempting to speculate that evolution of the pathogenic
      subspecies involved loss of functional T2S via structural changes of PilA and
      additional genes, including those that encode some of the Tfp-secreted proteins.

PMID- 17435118
TI  - Uptake and intracellular fate of Francisella tularensis in human macrophages.
AB  - Francisella tularensis is an intracellular pathogen that survives and multiplies
      within host mononuclear phagocytes. We have shown that uptake of the bacterium by
      human macrophages occurs by a novel process, "looping phagocytosis," in which the
      bacterium is engulfed in a spacious, asymmetric, pseudopod loop. Whereas looping
      phagocytosis is resistant to treatment of the F. tularensis with formalin,
      proteases, or heat, the process is abolished by oxidation of the bacterial
      carbohydrates with periodate, suggesting a role for preformed surface
      carbohydrate molecules in triggering looping phagocytosis. Following uptake, F.
      tularensis initially resides in a spacious vacuole at the periphery of the cell,
      but this vacuole rapidly shrinks in size. The nascent F. tularensis vacuole
      transiently acquires early endosomal markers, but subsequently exhibits an
      arrested maturation, manifest by only limited amounts of lysosome-associated
      membrane glycoproteins (consistent with limited interaction with late endosomes),
      nonfusion with lysosomes, and minimal acidification. In ultrastructural studies,
      we have observed that the F. tularensis phagosome displays a novel feature in
      that many of the phagosomes acquire an electron dense fibrillar coat. This
      fibrillar coat forms blebs and vesicles, and with time, is seen to be fragmented
      and disrupted. With increasing time after infection, increasing numbers of the F.
      tularensis are found free in the macrophage cytoplasm, such that by 14 h after
      infection, less than 15% of the bacteria are surrounded by any discernible
      phagosomal membrane. Further research is needed to determine the mechanisms
      underlying looping phagocytosis, and the maturational arrest, fibrillar coat
      formation, and disruption of the phagosome.

PMID- 17435119
TI  - Plastic corticostriatal circuits for action learning: what's dopamine got to do
      with it?
AB  - Reentrant corticobasal ganglia circuits are important for voluntary action and
      for action selection. In vivo and ex vivo studies show that these circuits can
      exhibit a plethora of short- and long-lasting plastic changes. Convergent
      evidence at the molecular, cellular, and circuit levels indicates that
      corticostriatal circuits are involved in the acquisition and automatization of
      novel actions. There is strong evidence that activity in corticostriatal circuits
      changes during the learning of novel actions, but the plastic changes observed
      during the early stages of learning a novel action are different than those
      observed after extensive training. A variety of studies indicate that the neural
      mechanisms and the corticostriatal subcircuits involved in the initial
      acquisition of actions and skills differ from those involved in their
      automatization or in the formation of habits. Dopamine, a critical modulator of
      short- and long-term plasticity in corticostriatal circuits, is differentially
      involved in early and late stages of action learning. Changes in dopaminergic
      transmission have several concomitant effects in corticostriatal function, which
      may be important for action selection and action learning. These diverse effects
      may subserve different roles for dopamine in reinforcement and action learning.

PMID- 17435120
TI  - Molecular epidemiology, evolution, and ecology of Francisella.
AB  - Tularemia is a disease caused by several subspecies of Francisella tularensis,
      although the severity of the disease varies greatly from subspecies to
      subspecies. Currently, there are four recognized subspecies (tularensis,
      holarctica, mediasiatica, and novicida), in addition to a second Francisella
      species, F. philomiragia. It is clear from molecular sampling of the environment
      that these human pathogens are a mere fraction of the Francisella diversity.
      Taxonomic nomenclature is now being based upon several DNA-sequence-based
      approaches and this advance provides for robust phylogenetic models that are
      guiding the systematics of this genus. This in turn allows for better molecular
      epidemiological investigations and more precise ecological analysis. Tularemia
      ecology is still only partially understood, with many knowledge gaps about the
      disease reservoir and vectors. Molecular analysis has identified a major
      population split within F. tularensis subsp. tularensis that points toward
      distinctive ecological adaptations, vectors, and host species. Current medical
      practice does not rely upon subspecies or subpopulation identification, although
      this information may have predictive value for clinical outcome, especially in
      the United States. Combined molecular and epidemiological analyses suggest that
      the population split in F. tularensis subsp. tularensis matches two distinct
      human diseases in the United States with different mortality rates. DNA-sequence
      based typing of F. tularensis subsp. holarctica from tularemia outbreaks in
      Europe and the United States proves regional identity among isolates and also
      demonstrates that this subspecies successfully disseminated worldwide in recent
      evolutionary time.

PMID- 17435121
TI  - Receptor theory and biological constraints on value.
AB  - Modern economic theories of value derive from expected utility theory. Behavioral
      evidence points strongly toward departures from linear value weighting, which has
      given rise to alternative formulations that include prospect theory and rank
      dependent utility theory. Many of the nonlinear forms for value assumed by these
      theories can be derived from the assumption that value is signaled by
      neurotransmitters in the brain, which obey simple laws of molecular movement.
      From the laws of mass action and receptor occupancy, we show how behaviorally
      observed forms of nonlinear value functions can arise.

PMID- 17435122
TI  - Francisella tularensis genomics and proteomics.
AB  - The availability of the genome sequences of different strains of Francisella
      tularensis is having a major impact on a wide range of research projects, from
      understanding the biology of this organism to devising vaccines and diagnostics.
      Comparative genomics and molecular typing methods suggest that the four different
      subspecies of F. tularensis are genetically distinct groups. Although there is a
      high degree of nucleotide identity between strains, there are numerous DNA
      rearrangements. IS elements appear to have played a major role in these
      chromosomal rearrangements. The different subspecies of F. tularensis appear to
      have evolved by vertical descent from a common ancestor, probably F. tularensis
      subspecies novicida. Comparative genomic and proteomic studies have revealed
      possible reasons for the different virulence of different strains and a range of
      candidate virulence genes have been identified including those located on the
      Francisella pathogenicity island. Proteomic studies have identified proteins
      which are produced at elevated levels in vivo, and proteins which are recognized
      by immune or convalescent sera. These proteins might be exploited as components
      of vaccines or diagnostic systems.

PMID- 17435123
TI  - Uterine contractility: visualization of synchronization measures in two
      simultaneously recorded signals.
AB  - The analysis of the uterine contraction signals in nonpregnant states gives
      information about physiological changes during the menstrual cycle. Spontaneous
      uterine activity was recorded directly by a dual microtip catheter. The device
      consisted of two ultra-miniature pressure sensors. One sensor was placed in the
      fundus, the other in the cervix. It was important to identify time delays between
      contractions in two topographic locations, which may be of potential diagnostic
      significance in various pathologies: dysmenorrhea, endometriosis, and fecundity
      disorders. In this study the following synchronization measures-the cross
      correlation, the semblance, the mutual information-were used to visualize the
      time delay changes over time. These measures were computed in a moving window
      with a width corresponding to approximately two or three contractions. As a
      result, the running synchronization functions were obtained. The running
      synchronization functions visualize changes in the propagation of the two
      simultaneously recorded signals. The propagation% parameter assessed from these
      functions allows for quantitative description of synchronization. Finally, we
      illustrate the use of running synchronization functions to investigate the effect
      of treatment with tamoxifen on primary dysmenorrhea.

PMID- 17435124
TI  - Multiple representations of belief states and action values in corticobasal
      ganglia loops.
AB  - Reward-related neural activities have been found in a variety of cortical and
      subcortical areas by neurophysiological and neuroimaging experiments. Here we
      present a unified view on how three subloops of the corticobasal ganglia network
      are involved in reward prediction and action selection using different types of
      information. The motor/premotor-posterior striatum loop is specialized for action
      based value representation and movement selection. The orbitofrontal-ventral
      striatum loop is specialized for object-based value representation and target
      selection. The lateral prefrontal-anterior striatum loop is specialized for
      context-based value representation and context estimation. Furthermore, the
      medial prefrontal cortex (MPFC) coordinates these multiple value representations
      and actions at different levels of hierarchy by monitoring the error in
      predictions.

PMID- 17435125
TI  - Oral-based diagnostics. Festschrift to honor Irwin Mandel and proceedings of a
      conference. October 10-12, 2006. Lake Lanier Islands, Georgia, USA.

PMID- 17435127
TI  - Genomic targets in saliva.
AB  - Saliva, the most accessible and noninvasive biofluid of our body, harbors a wide
      spectrum of biological analytes informative for clinical diagnostic applications.
      While proteomic constituents are a logical first choice as salivary diagnostic
      analytes, genomic targets have emerged as highly informative and discriminatory.
      This awareness, coupled with the ability to harness genomic information by high
      throughput technology platforms such as genome-wide microarrays, ideally
      positions salivary genomic targets for exploring the value of saliva for
      detection of specific disease states and augmenting the diagnostic and
      discriminatory value of the saliva proteome for clinical applications. Buccal
      cells and saliva have been used as sources of genomic DNA for a variety of
      clinical and forensic applications. For discovery of disease targets in saliva,
      the recent realization that there is a transcriptome in saliva presented an
      additional target for oral diagnostics. All healthy subjects evaluated have
      approximately 3,000 different mRNA molecules in their saliva. Almost 200 of these
      salivary mRNAs are present in all subjects. Exploration of the clinical utility
      of the salivary transcriptome in oral cancer subjects shows that four salivary
      mRNAs (OAZ, SAT, IL8, and IL1b) collectively have a discriminatory power of 91%
      sensitivity and specificity for oral cancer detection. Data are also now in place
      to validate the presence of unique diagnostic panels of salivary mRNAs in
      subjects with Sjogren's disease.

PMID- 17435128
TI  - Saliva and the clinical pathology laboratory.
AB  - There have been increasing numbers of applications using oral fluids, saliva in
      particular, as the target substrate for performing clinical diagnostic tests.
      These have focused primarily on point-of-care (POC) testing. These POC testing
      approaches range from, for example, currently available, highly specialized
      screening tests for the presence of antibodies recognizing HIV to the potential
      development of "lab-on-a-chip" platforms. Broad claims have been made that the
      latter will revolutionize clinical laboratory testing. From the perspective of
      large centralized clinical laboratories, multiple issues must be considered
      before implementing individual tests using saliva as the target fluid in a POC
      format or using saliva as a universal test fluid for measuring multiple analytes
      in a centralized laboratory format. The current scope of laboratory testing is
      large and comprehensive, involving both POC and centralized testing. Current
      academic laboratory programs have the ability to qualitatively identify and/or
      quantitatively measure several thousand analytes in various target matrices
      including blood, plasma, serum, urine, joint fluid, pleural fluid, peritoneal
      fluid, cerebrospinal fluid, and tissue. These tests fall into multiple clinical
      pathology disciplines, including clinical chemistry, hematology, coagulation,
      transfusion medicine, microbiology, cytogenetics, molecular diagnosis, and
      immunology. In addition, before implementing a given test, multiple issues need
      to be evaluated to ensure the validity of the reported result; these include
      considerations involving the three major phases of testing: preanalytical (e.g.,
      patient identification and specimen collection, stability, and transport),
      analytical (e.g., sensitivity, specificity, accuracy, and precision), and
      postanalytical (e.g., reporting results, quality improvement, and turn-around
      time).

PMID- 17435129
TI  - Oral diseases: from detection to diagnostics.
AB  - In addition to saliva, other oral components such as gingival crevicular fluid,
      epithelial cells, bacteria, breath, and dental plaque have diagnostic potential.
      For oral diseases such as caries and periodontal disease, visual diagnosis is
      usually adequate, but objective diagnostic tests with predictive value are
      desired. Therefore, prediction models like the Cariogram have been developed that
      also include oral aspects such as saliva secretion, buffering capacity, and
      Streptococcus mutans counts for the prediction of caries. Correlation studies on
      salivary components and caries have not been conclusive, but correlation studies
      on functional aspects, such as saliva-induced bacterial aggregation and caries,
      look promising. Modern proteomic techniques make it possible to study
      simultaneously the many salivary components involved in these functions.

PMID- 17435130
TI  - A novel caries risk test.
AB  - A diagnostic test is particularly beneficial if it reveals the level of
      susceptibility prior to onset of a disease process. In the case of childhood
      caries, such a diagnostic test affords the opportunity for preventive measures to
      be implemented before caries begins. Salivary glycoproteins contain a wealth of
      individually specific oligosaccharide motifs. Depending on microbial
      compatibilities and individual genotypes, the glycoproteins that form the
      pellicle coating of teeth may provide attachment sites that foster colonization
      leading to cariogenesis. Alternatively, certain oligosaccharides, when present in
      nonpellicle glycoproteins, can interact with planktonic bacteria and lower their
      ability to interact with the tooth surface. We have found that in young adults
      the ratio of the two classes of oligosaccharides present in resting saliva
      exhibits a strong correlation with caries history (DFT: number of decayed and
      filled teeth). Oligosaccharide moieties associated with the test are quantitated
      in dried spots of whole saliva on nitrocellulose using commercially available
      biotinylated lectins with a variety of reporters. A combination of multiple
      linear regression and neural net analyses were used to develop the algorithms
      that describe the relationship between oligosaccharide patterns and DFT. During
      test development several different groups of adults and children have been
      studied. The correlation algorithms routinely exceed an R(2) (coefficient of
      determination) of 0.96. When the test is applied to the saliva of children, it
      yields a projection of their future caries history. Modifying the test result
      metric to reflect the groups of teeth with caries in young adults, the test
      identifies those teeth at risk for future caries in children. This test outcome
      can then be accompanied with suggested specific preventive measures for each
      tooth group-based risk level.

PMID- 17435131
TI  - Analysis of gingival crevicular fluid as applied to the diagnosis of oral and
      systemic diseases.
AB  - Gingival crevicular fluid (GCF), a serum transudate or inflammatory exudate, can
      be collected from the gingival crevice surrounding the teeth. As such, the fluid
      reflects the constituents of serum, the cellular response in the periodontium,
      and contributions from the gingival crevice. The study of GCF has focused on
      defining the pathophysiology of periodontal disease, and identification of a
      potential diagnostic test for active periodontitis. The majority of markers that
      have been identified as potential candidates for such a test are measures of
      inflammation (i.e., prostaglandin E2 (PGE2), neutrophil elastase, and the
      lysosomal enzyme beta-glucuronidase). Further, analysis of inflammatory markers
      in GCF may assist in defining how certain systemic disorders (e.g., diabetes
      mellitus) can modify periodontal disease, and how periodontal disease/periodontal
      inflammation can influence certain systemic disorders (i.e.,
      cardiovascular/cerebrovascular diseases). Methodological concerns related to the
      collection and analysis of GCF are important factors that need to be considered
      when studying GCF. Practical concerns argue against the widespread clinical
      application of GCF as an adjunct to periodontal diagnosis. Rather, analysis of
      GCF-derived mediators in saliva may serve as a means of rapid screening for
      periodontal disease.

PMID- 17435133
TI  - Human breath odors and their use in diagnosis.
AB  - Humans emit a complex array of volatile and nonvolatile molecules that are
      influenced by an individual's genetics, health, diet, and stress. Olfaction is
      the most ancient of our distal senses and may be used to evaluate food and
      environmental toxins as well as recognize kin and potential predators. Many body
      odors evolved to be olfactory messengers, which convey information between
      individuals. Consequently, those practicing the healing arts have used olfaction
      to aid in their diagnosis of disease since the dawn of medical practice. Studies
      using modern instrumental analyses have focused upon analysis of breath volatiles
      for biomarkers of internal diseases. In these studies, a subject's oral health
      status appears to seldom be considered. However, saliva and properly collected
      alveolar air samples must pass over or come in contact with the posterior dorsal
      surface of the tongue, a site of bacterial plaque development and source of
      halitosis-related volatiles. Because of our basic research into the nature of
      human body odors, our lab has received referrals of people with idiopathic
      malodor production, from either the oral cavity or body. We developed a protocol
      to help differentiate individuals with chronic halitosis from those with the
      genetic, odor-producing metabolic disorder trimethylaminuria (TMAU). In our
      referred population, TMAU is the largest cause of undiagnosed body odor. Many
      TMAU-positive individuals present with oral symptoms of dysguesia and halitosis
      as well as body odor. We present data regarding the presentation of our referred
      subjects as well as the analytical results from a small number of these subjects
      regarding their oral levels of halitosis-related malodorants and trimethylamine.

PMID- 17435134
TI  - Molecular and protein markers of disease.
AB  - Oral fluid diagnostics are becoming a part of routine care. The key to their use
      is to correctly interpret their findings so that patients' well-being can be
      optimized.

PMID- 17435132
TI  - Oral fluid-based biomarkers of alveolar bone loss in periodontitis.
AB  - Periodontal disease is a bacteria-induced chronic inflammatory disease affecting
      the soft and hard supporting structures encompassing the teeth. When left
      untreated, the ultimate outcome is alveolar bone loss and exfoliation of the
      involved teeth. Traditional periodontal diagnostic methods include assessment of
      clinical parameters and radiographs. Though efficient, these conventional
      techniques are inherently limited in that only a historical perspective, not
      current appraisal, of disease status can be determined. Advances in the use of
      oral fluids as possible biological samples for objective measures of current
      disease state, treatment monitoring, and prognostic indicators have boosted
      saliva and other oral-based fluids to the forefront of technology. Oral fluids
      contain locally and systemically derived mediators of periodontal disease,
      including microbial, host-response, and bone-specific resorptive markers.
      Although most biomarkers in oral fluids represent inflammatory mediators, several
      specific collagen degradation and bone turnover-related molecules have emerged as
      possible measures of periodontal disease activity. Pyridinoline cross-linked
      carboxyterminal telopeptide (ICTP), for example, has been highly correlated with
      clinical features of the disease and decreases in response to intervention
      therapies, and has been shown to possess predictive properties for possible
      future disease activity. One foreseeable benefit of an oral fluid-based
      periodontal diagnostic would be identification of highly susceptible individuals
      prior to overt disease. Timely detection and diagnosis of disease may
      significantly affect the clinical management of periodontal patients by offering
      earlier, less invasive, and more cost-effective treatment therapies.

PMID- 17435135
TI  - Subclinical cardiovascular disease markers applicable to studies of oral health:
      multiethnic study of atherosclerosis.
AB  - Recent findings associate periodontal disease with established coronary heart
      disease (CHD) and with disorders of the carotid artery. Besides measures of the
      carotid artery, a number of other noninvasive subclinical markers of
      cardiovascular disease exist and are summarized here. Included are computed
      tomography (CT) of the coronary arteries, ultrasound of the carotid arteries,
      echocardiography, magnetic resonance imaging (MRI), ankle-brachial index,
      microalbuminuria, and other biochemical measures of kidney dysfunction, flow
      mediated dilation in the brachial artery, and pulse wave form analysis. Use of
      these measures may simplify and add depth to studies of oral health and
      cardiovascular disease. However, it is noted that the measures are not highly
      correlated with each other (based on 6,814 persons in the Multiethnic Study of
      Atherosclerosis, Pearson correlations among the above subclinical measures, range
      from about 0.1-0.4), do not include propensity for the important atherosclerotic
      phase of plaque rupture, and do not fully substitute for studies of clinical
      cardiovascular disease endpoints.

PMID- 17435136
TI  - Do salivary antibodies reliably reflect both mucosal and systemic immunity?
AB  - Two major antibody classes operate in saliva: secretory IgA (SIgA) and IgG. The
      former is synthesized as dimeric IgA by plasma cells (PCs) in salivary glands and
      is exported by the polymeric Ig receptor (pIgR). Most IgG in saliva is derived
      from serum (mainly via gingival crevices), although some is locally produced. Gut
      associated lymphoid tissue (GALT) and nasopharynx-associated lymphoid tissue
      (NALT) do not contribute equally to mucosal PCs throughout the body. Thus,
      enteric immunostimulation is an inadequate mode of stimulating salivary IgA
      antibodies, which are poorly associated with the intestinal SIgA response, for
      instance after enteric cholera vaccination. Nevertheless, the IgA response in
      submandibular/sublingual glands is better related to B cell induction in GALT
      than the parotid response. Such disparity is suggested by the elevated levels of
      IgA in submandibular secretions of AIDS patients, paralleling their highly
      upregulated intestinal IgA system. Moreover, in patients with active celiac
      disease, IgA antibodies to disease-precipitating gliadin are reliably represented
      in whole saliva but not in parotid secretion. Parotid SIgA may be more
      consistently linked to immune induction in palatine tonsils and adenoids (human
      NALT), as supported by the homing molecule profile of NALT-derived B cell blasts.
      Also several other variables influence the levels of antibodies in oral
      secretions. These include difficulties with reproducibility and standardization
      of immunoassays, the impact of flow rate, acute or chronic stress, protein loss
      during sample handling, and uncontrolled admixture of serum-derived IgG and
      monomeric IgA. Despite such problems, saliva remains an interesting biological
      fluid with great scientific and clinical potentials.

PMID- 17435137
TI  - Oxytocin: behavioral associations and potential as a salivary biomarker.
AB  - Oxytocin (OT) is a neuropeptide that is produced primarily in the hypothalamus
      and is best known for its role in mammalian birth and lactation. Recent evidence
      also implicates OT in social behaviors, including parental behavior, the
      formation of social bonds, and the management of stressful experiences. OT is
      reactive to stressors, and plays a role in the regulation of both the central and
      autonomic nervous system, including effects on immune and cardiovascular
      function. Knowledge of patterns of OT release would be of value in many fields of
      science and medicine. However, measurements of OT concentration in blood are
      infrequently performed, and previous attempts to measure OT in saliva have been
      unsuccessful. Using a sensitive enzyme immunoassay (EIA) and concentrated samples
      we were able to detect reproducible changes in salivary OT as a function of
      lactation and massage. These results indicate that measurements of biologically
      relevant changes in salivary OT are possible. These results confirm the
      biological relevance of changes in salivary OT with stressors and support saliva
      as a noninvasive source to monitor central neuroendocrine function.

PMID- 17435138
TI  - Human saliva proteome analysis.
AB  - Human saliva contains proteins that can be informative for disease detection and
      surveillance of oral health. Comprehensive analysis and identification of the
      proteomic content in human whole and ductal saliva is a necessary first step
      toward the discovery of saliva protein markers for human disease detection. The
      article will review the recent advances in human saliva proteome analysis,
      including the efforts of the UCLA saliva proteome consortium funded by the
      National Institute of Dental and Craniofacial Research (NIDCR). We aim to
      summarize the proteomics technologies currently used for global analysis of
      saliva proteins and to elaborate on the application of saliva proteomics to
      discovery of disease biomarkers, in particular for oral cancer and Sjogren's
      syndrome, and discuss some of the critical challenges and perspectives for this
      emerging field. The impact of human saliva proteome analysis in the search for
      clinically relevant disease biomarkers will be realized through advances made
      using proteomics technologies.

PMID- 17435139
TI  - Genomics and proteomics: the potential role of oral diagnostics.
AB  - Advances in genomics and proteomics increasingly contribute to the understanding
      of signal transduction pathways that control growth, differentiation, and death
      of cells. Since defects in these processes may result in the expression of
      inherited and or acquired disease, the identification of candidate disease genes
      and modifier genes by parallel use of genotyping together with an integrated
      study of gene expression and metabolite levels is instrumental for future health
      care. This approach, called systems biology, aims to recognize early onset of
      disease, institute preventive treatment, and identify new molecular targets for
      novel drugs in cancer, cardiovascular and metabolomic disease (e.g., diabetes),
      and neurodegenerative disorders. Gene interaction networks have recently been
      demonstrated, in which hub genes, that is, genes that show the highest level of
      interactions with other genes, play a special role. Hub genes, often chromatin
      regulators, may act as modifier genes (genes that modify the effect of other
      genes) in multiple mechanistically unrelated genetic diseases in humans. In
      addition, it has been shown that small metabolites such as hormones and
      cytokines, or proteins/enzymes such as C reactive protein (C-RP) and matrix
      metaloproteinase (MMP), reflect disease status in case of oral cancer, asthma, or
      periodontal and cardiac disease. Many of these molecular targets, as well as
      pathogen-specific DNA and RNA sequences, can be measured in oral fluids,
      providing a unique opportunity to develop novel noninvasive diagnostic tests.
      Efforts so far concentrate on the use of lab-on-a-chip technology in combination
      with novel reporters and microsensor arrays to measure multianalytes in oral
      fluids. Handheld devices that perform sensitive detection of multiple analytes in
      oral fluid will be obtainable in the near future.

PMID- 17435140
TI  - SPR imaging-based salivary diagnostics system for the detection of small molecule
      analytes.
AB  - Saliva is an underused fluid with considerable promise for biomedical testing.
      Its potential is particularly great for monitoring small-molecule analytes since
      these are often present in saliva at concentrations that correlate well with
      their free levels in blood. We describe the development of a prototype diagnostic
      device for the rapid detection of the antiepileptic drug (AED) phenytoin in
      saliva. The multicomponent system includes a hand-portable surface plasmon
      resonance (SPR) imaging instrument and a disposable microfluidic assay card.

PMID- 17435141
TI  - Saliva-based diagnostics using 16S rRNA microarrays and microfluidics.
AB  - The development of a diagnostic system based on DNA microarrays for rapid
      identification and enumeration of microbial species in the oral cavity is
      described. This system uses gel-based microarrays with immobilized probes
      designed within a phylogenetic framework that provides for comprehensive
      microbial monitoring. Understanding the community structure in the oral cavity is
      a necessary foundation on which to understand the breadth and depth of different
      microbial communities in the oral cavity and their role in acute and systemic
      disease. Our ultimate goal is to develop a diagnostic device to identify
      individuals at high risk for oral disease, and thereby reduce its prevalence and
      therefore the economic burden associated with treatment. This article discusses
      recent improvements of our system in reducing diffusional constraints in order to
      provide more rapid and accurate measurements of the microbial composition of
      saliva.

PMID- 17435142
TI  - Integrated microfluidic platform for oral diagnostics.
AB  - While many point-of-care (POC) diagnostic methods have been developed for blood
      borne analytes, development of saliva-based POC diagnostics is in its infancy. We
      have developed a portable microfluidic device for detection of potential
      biomarkers of periodontal disease in saliva. The device performs rapid
      microfluidic chip-based immunoassays (<3-10 min) with low sample volume
      requirements (10 microL) and appreciable sensitivity (nM-pM). Our microfluidic
      method facilitates hands-free saliva analysis by integrating sample pretreatment
      (filtering, enrichment, mixing) with electrophoretic immunoassays to quickly
      measure analyte concentrations in minimally pretreated saliva samples. The
      microfluidic chip has been integrated with miniaturized electronics, optical
      elements, such as diode lasers, fluid-handling components, and data acquisition
      software to develop a portable, self-contained device. The device and methods are
      being tested by detecting potential biomarkers in saliva samples from patients
      diagnosed with periodontal disease. Our microchip-based analysis can readily be
      extended to detection of biomarkers of other diseases, both oral and systemic, in
      saliva and other oral fluids.

PMID- 17435143
TI  - Development of a microfluidic device for detection of pathogens in oral samples
      using upconverting phosphor technology (UPT).
AB  - Confirmatory detection of diseases, such as HIV and HIV-associated pathogens in a
      rapid point-of-care (POC) diagnostic remains a goal for disease control,
      prevention, and therapy. If a sample could be analyzed onsite with a verified
      result, the individual could be counseled immediately and appropriate therapy
      initiated. Our group is focused on developing a microfluidic "lab-on-a-chip" that
      will simultaneously identify antigens, antibodies, RNA, and DNA using a single
      oral sample. The approach has been to design individual modules for each assay
      that uses similar components (e.g., valves, heaters, metering chambers, mixers)
      installed on a polycarbonate base with a common reporter system. Assay
      miniaturization reduces the overall analysis time, increases accuracy by
      simultaneously identifying multiple targets, and enhances detector sensitivity by
      upconverting phosphor technology (UPT). Our microfluidic approach employs four
      interrelated components: (1) sample acquisition-OraSure UPlink collectors that
      pick-up and release bacteria, soluble analytes, and viruses from an oral sample;
      (2) microfluidic processing-movement of microliter volumes of analyte, target
      analyte extraction and amplification; (3) detection of analytes using UPT
      particles in a lateral flow system; and (4) software for processing the results.
      Ultimately, the oral-based microscale diagnostic system will detect viruses and
      bacteria, associated pathogen antigens and nucleic acids, and antibodies to these
      pathogens.

PMID- 17435144
TI  - Microsensor arrays for saliva diagnostics.
AB  - Optical fiber microarrays have been used to screen saliva from patients with end
      stage renal disease (ESRD) to ascertain the efficacy of dialysis. We have
      successfully identified markers in saliva that correlate with kidney disease.
      Standard assay chemistries for these markers have been converted to disposable
      test strips such that patients may one day be able to monitor their clinical
      status at home. Details of these developments are described. In addition, saliva
      from asthma and chronic obstructive pulmonary disease (COPD) patients is being
      screened for useful diagnostic markers. Our goal is to develop a multiplexed
      assay for these protein and nucleic acid biomarkers for diagnosing the cause and
      severity of pulmonary exacerbations, enabling more effective treatment to be
      administered. These results are reported in the second part of this article.

PMID- 17435145
TI  - Oral fluid nanosensor test (OFNASET) with advanced electrochemical-based
      molecular analysis platform.
AB  - High-impact diseases, including cancer, cardiovascular disease, and neurological
      disease, are challenging to diagnose without supplementing clinical evaluation
      with laboratory testing. Even with laboratory tools, definitive diagnosis often
      remains elusive. The lack of three crucial elements presents a road block to
      achieving the potential of clinical diagnostic tests: (1) definitive disease
      associated protein and genetic markers, (2) easy and inexpensive sampling methods
      with minimal discomfort for the subject, and (3) an accurate and quantitative
      diagnostic platform. Our aim is to develop and validate a solution for
      requirement (3) and also to develop a portable system. Requirements (1) and (2)
      will be addressed through the utilization of novel and highly specific oral
      cancer saliva proteomic and genomic biomarkers and the use of saliva as the
      biofluid of choice, respectively. The Oral Fluid NanoSensor Test (OFNASET)
      technology platform combines cutting-edge technologies, such as self-assembled
      monolayers (SAM), bionanotechnology, cyclic enzymatic amplification, and
      microfluidics, with several well-established techniques including microinjection
      molding, hybridization-based detection, and molecular purification. The intended
      use of the OFNASET is for the point of care multiplex detection of salivary
      biomarkers for oral cancer. We have demonstrated that the combination of two
      salivary proteomic biomarkers (thioredoxin and IL-8) and four salivary mRNA
      biomarkers (SAT, ODZ, IL-8, and IL-1b) can detect oral cancer with high
      specificity and sensitivity. Our preliminary studies have shown compelling
      results. We sequentially delivered a serial dilution of IL-8 antigen, probe
      solution, wash, enzyme solution, wash, and mediator solution to sensor reaction
      chambers housed in a prototype cartridge and demonstrated strong signal
      separation at 50 pg/mL above a negative control.

PMID- 17435146
TI  - Lab-on-a-chip methods for point-of-care measurements of salivary biomarkers of
      periodontitis.
AB  - Salivary secretions contain a variety of molecules that reflect important
      pathophysiological activities. Quantitative changes of specific salivary
      biomarkers could have significance in the diagnosis and management of both oral
      and systemic diseases. Modern point-of-care technologies with enhanced detection
      capabilities are needed to implement a significant advancement in salivary
      diagnostics. One such promising technology is the recently described lab-on-a
      chip (LOC) assay system, in which assays are performed on chemically sensitized
      beads populated into etched silicon wafers with embedded fluid handling and
      optical detection capabilities. Using this LOC system, complex assays can be
      performed with small sample volumes, short analysis times, and markedly reduced
      reagent costs. This report describes the use of LOC methodologies to assess the
      levels of interleukin-1beta (IL-1beta), C-reactive protein (CRP), and matrix
      metalloproteinase-8 (MMP-8) in whole saliva, and the potential use of these
      biomarkers for diagnosing and categorizing the severity and extent of
      periodontitis. This study demonstrates that the results achieved by the LOC
      approach are in agreement with those acquired with standard enzyme-linked
      immunosorbent assay (ELISA), with significant IL-1beta and MMP-8 elevations in
      whole saliva of periodontitis patients. Furthermore, because of the superior
      detection capacities associated with the LOC approach, unlike those with ELISA,
      significant differences in CRP levels between periodontitis patients and normal
      subjects are observed. Finally, principal component analysis (PCA) is performed
      to yield an efficient method to discriminate between periodontally healthy and
      unhealthy patients, thus increasing the diagnostic value of these biomarkers for
      periodontitis when examined with the integrated LOC sensor system.

PMID- 17435147
TI  - A microfluidic system for saliva-based detection of infectious diseases.
AB  - A "lab-on-a-chip" system for detecting bacterial pathogens in oral fluid samples
      is described. The system comprises: (1) an oral fluid sample collector; (2) a
      disposable, plastic microfluidic cassette ("chip") for sample processing
      including immunochromatographic assay with a nitrocellulose lateral flow strip;
      (3) a platform that controls the cassette operation by providing metered
      quantities of reagents, temperature regulation, valve actuation; and (4) a laser
      scanner to interrogate the lateral flow strip. The microfluidic chip hosts a
      fluidic network for cell lysis, nucleic acid extraction and isolation, PCR, and
      labeling of the PCR product with bioconjugated, upconverting phosphor particles
      for detection on the lateral flow strip.

PMID- 17435148
TI  - Rapid assay format for multiplex detection of humoral immune responses to
      infectious disease pathogens (HIV, HCV, and TB).
AB  - A novel assay is described for multiplex detection of antibodies against
      different pathogens from a single sample. The assay employs a modified lateral
      flow format (consecutive flow, CF) together with a sensitive reporter particle
      technology (up-converting phosphor technology, UPT) that allows for fully
      instrumented assay analysis. Lateral flow (LF) strips developed for the detection
      of human antibodies against human immunodeficiency virus type-1 and -2 (HIV-1 and
      -2) with additional capture zones to detect antibodies against Myobacterium
      tuberculosis (TB) and hepatitis C Virus (HCV) provided the strips to test
      multiplexing. Data are presented that show the performance of the TB and HCV
      test, as well as two multiplex assays, TB with HIV and HCV with HIV. The TB/HCV
      assays demonstrate excellent detection capability, and HIV multiplexing does not
      affect the qualitative test result. The bench-top CF format was converted to a
      microfluidic platform and a first prototype semiautomated chip capable of
      performing CF is presented here.

PMID- 17435149
TI  - Patterns of salivary estradiol and progesterone across the menstrual cycle.
AB  - The aim of this study was to characterize the normality of menstrual cycles on
      the basis of progesterone and estradiol levels in self-collected saliva samples.
      Twenty-two women, ages 19-40 years, self-collected whole unstimulated saliva
      specimens each morning for two consecutive menstrual cycles. On the basis of
      presence/timing of hormone peaks, two investigators classified 24 cycles as
      normal, 10 as likely normal, and 10 as clearly not normal with respect to
      expected profiles. Our results show that whole saliva samples collected at home
      on a daily basis provide a noninvasive, feasible method of determining menstrual
      cycle profiles.

PMID- 17435150
TI  - Layered peptide arrays: a diverse technique for antibody screening of clinical
      samples.
AB  - The layered peptide array (LPA) is a recently developed technique designed to
      measure antibody levels in a multiplex, high-throughput manner. LPAs can assess
      antibody presence either in fluid samples or from tissues while maintaining the
      two-dimensional orientation of the life science platform. In this manuscript, we
      evaluated and assessed the performance of the LPA platform, focusing on
      throughput capability, sensitivity, and specificity of the assay in several
      different systems.

PMID- 17435151
TI  - Whole saliva proteolysis: wealth of information for diagnostic exploitation.
AB  - Whole saliva (WS) protein profiles differ significantly from those of glandular
      salivary secretions. Rapid proteolysis of the prominent members of the salivary
      protein families by WS resident proteases appears to be a major cause for the
      observed differences. We propose that the rate and mode of glandular salivary
      protein degradation in the oral cavity contains information that could be of
      unique value in the diagnosis of oral disease.

PMID- 17435152
TI  - Saliva-based HIV testing among secondary school students in Tanzania using the
      OraQuick rapid HIV1/2 antibody assay.
AB  - HIV prevalence and knowledge concerning HIV prevention among secondary school
      students in Tanzania was investigated. Approximately 50% of all secondary school
      students in Hai district and Moshi town were included in the study. Saliva
      samples were obtained using the OraQuick rapid HIV-1/2 antibody assay. Forty-one
      (1.0%) and 211 (5.5%) students at the rural and urban schools, respectively,
      tested positive for HIV antibodies in saliva. HIV knowledge and beliefs varied
      significantly. Noninvasive saliva sample collection for HIV testing was highly
      acceptable. HIV infection is considerably more widespread among students
      attending urban rather than rural schools in the population investigated.

PMID- 17435153
TI  - Lab-on-a-chip technologies for oral-based cancer screening and diagnostics:
      capabilities, issues, and prospects.
AB  - The design of a microfluidic lab-on-a-chip system for point-of-care cancer
      screening and diagnosis of oral squamous cell carcinoma (OSCC) is presented. The
      chip is based on determining a approximately 30-gene transcription profile in
      cancer cells isolated from oral fluid samples. Microfluidic cell sorting using
      magnetic beads functionalized with an antibody against cancer-specific cell
      surface antigens (e.g., epithelial cell adhesion molecule [EpCAM]) is described.
      A comprehensive cancer diagnostics chip will integrate microfluidic components
      for cell lysis, nucleic acid extraction, and amplification and detection of a
      panel of mRNA isolated from a subpopulation of cancer cells contained in a
      clinical specimen.

PMID- 17435154
TI  - Evaluation of UPlink-RSV: prototype rapid antigen test for detection of
      respiratory syncytial virus infection.
AB  - A prototype rapid antigen test for the on-site detection of respiratory syncytial
      virus (RSV) infection was developed and evaluated. The platform uses instrumented
      assay analysis, eliminating potential operator bias in the interpretation of the
      test result that may occur with visually interpreted rapid antigen assays. The
      device was tested as the first point-of-care (POC) infectious disease application
      of novel reporter up-converting phosphor technology (UPT) using a specifically
      designed portable UPT reader (UPlink). Assays were performed by mixing
      nasopharyngeal specimen with RSV-specific UPT reporter particles and addition of
      the mixture to a disposable cassette containing a lateral flow (LF) strip with
      RSV capture antibodies. UPT reporters bound on the specific capture zone were
      analyzed with the UPlink reader. Reproducibility testing of the UPlink-RSV (UPR)
      test by naive users confirmed the potential of UPlink for POC applications where
      testing is not always performed by highly trained medical staff. The performance
      of UPR was further evaluated with clinical nasopharyngeal specimens. A
      prospective study at an independent test site demonstrated clinical parameters of
      90% sensitivity and 98.3% specificity with an overall correlation of 96.2% as
      compared to viral culture with RT-PCR verification. These results are in
      agreement with in-house retrospective studies and results obtained with other
      available commercial rapid antigen assays.

PMID- 17435155
TI  - Immunoassay-based diagnostic point-of-care technology for oral specimen.
AB  - We have outlined our progress in developing a novel point-of-care platform to
      quantify micro-organisms causing dental infections and/or inflammatory markers
      reflecting an oral disease status. This system is based on a sandwich immunoassay
      technology known as ABICAP (Antibody Immuno Column for Analytical Processes)
      using poly-horseradish peroxidase conjugates. This assay enabled us to quantify
      500 colony-forming units of Streptococcus sobrinus per milliliter of saliva. The
      platform allows rapid and convenient performance chairside of such tests by a
      dentist or dental hygienist within 20 minutes at the dental office.

PMID- 17435156
TI  - Evaluation of immunoassay-based MMP-8 detection in gingival crevicular fluid on a
      point-of-care platform.
AB  - A novel immunology-based point-of-care test has been designed to assess the
      activated form of matrix metalloproteinase-8 (aMMP-8) for diagnosis and
      monitoring of periodontal diseases. The test has been automated using an
      analyzer, which quantitatively measures aMMP-8 in 18 min in gingival crevicular
      fluid (GCF). Fluid samples were collected from healthy, gingivitis-, and
      periodontitis-affected teeth. The test results from the analyzer were compared
      with quantitative aMMP-8 immunofluorometric assay (IFMA) and in-house enzyme
      linked immunosorbent assay (ELISA) as well as with the periodontal state.
      Preliminary results of analyzer measurements of these 34 clinical samples showed
      a good agreement with the results from IFMA and in-house ELISA and with the
      clinical picture.

PMID- 17435157
TI  - Rapid quantitative chairside test for active MMP-8 in gingival crevicular fluid:
      first clinical data.
AB  - In a first pilot field study 64 gingival crevicular fluid (GCF) samples were
      collected from patients of dental practitioners. The dentists (one orthodontist
      one periodontist, and one general practitioner) were asked to monitor the
      respective clinical status of the sites of sampling and to collect, if possible,
      sulcus fluid samples from healthy as well as affected sites from the same
      patient. The concentration of activated matrix metalloproteinase-8 (aMMP-8) in
      the GCF was recorded using a set of monoclonal antibodies and a novel
      DentoAnalyzer. From all three dental offices the distribution of the aMMP-8
      values in GCF showed a congruent pattern, where healthy and periodontitis
      affected inflamed sites were clearly disparate.

PMID- 17435158
TI  - Salivary biomarkers associated with alveolar bone loss.
AB  - A longitudinal case-control study was performed to measure the association of
      salivary biomarkers with alveolar bone loss from a sub-sample of 1,256 post
      menopausal women enrolled in the Buffalo Women's Health Initiative. From this
      cohort, 40 subjects with significant alveolar bone loss over a 5-year period were
      compared to 40 age-matched control subjects having no alveolar bone loss. Several
      biomarkers were quantitated in saliva collected at baseline by immunoassay. A
      positive association was noted between alveolar bone loss and salivary
      concentrations of hepatocyte growth factor, and interleukin-1 beta, while a
      negative association was noted for alveolar bone loss and salivary osteonectin.
      This study provides preliminary evidence that several salivary biomarkers
      measured at baseline may serve to predict future alveolar bone loss.

PMID- 17435159
TI  - Salivary protein/peptide profiling with SELDI-TOF-MS.
AB  - In this study, large-scale profiling of salivary proteins and peptides ranging
      from 2 to 100 kDa was demonstrated using surface-enhanced laser
      desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). Results
      show that chip surface type and sample type critically affect the amount and
      composition of detected salivary proteins. Delayed processing time resulted in
      both increase and decrease of peak numbers consistent with proteolysis. SELDI-TOF
      MS profiles also changed, depending on storage temperature, although sample
      processing by centrifugation and numbers of freeze-thaw cycles had a minimal
      impact. In conclusion, SELDI-TOF-MS offers a simple, rapid, high-throughput
      technique for profiling low-mass (<10 kDa) saliva proteins/peptides. We wish to
      use this technique to gain insight into the human saliva proteome composition and
      its changes over time in response to food consumption.

PMID- 17435160
TI  - Acquired enamel pellicle and its potential role in oral diagnostics.
AB  - The acquired enamel pellicle (AEP) is a protein film with unique composition and
      properties, which is formed by the selective adsorption of a variety of oral
      fluid-derived proteins onto tooth enamel surfaces. Since events leading to caries
      and periodontal disease occur in close proximity to the tooth surface, pellicle
      constituents are likely to contain biomarkers valuable for diagnostic
      applications. Despite the importance of this oral structure, progress in
      understanding its formation and composition has been slow because of difficulties
      in efficient pellicle collection methods and limitations of biochemical
      techniques for the characterization of microgram amounts of proteins/peptides.
      Recent developments in both pellicle collection methods and nanoscale sensing
      technologies have brought the exploitation of pellicle analysis into the realm of
      point-of-care oral diagnostics.

PMID- 17435161
TI  - Gender-specific differences in salivary biomarker responses to acute
      psychological stress.
AB  - The stress response is regulated by two primary neuroendocrine systems, the
      hypothalamus-pituitary-adrenocortical (HPA) and sympathetic adrenomedullary (SAM)
      systems. This study investigated gender differences in the activities of these
      two systems in response to acute psychological stress. Subjects were categorized
      according to their score in Spielberger's Trait Anxiety Inventory (STAI), which
      assesses the predisposition to personal anxiety. High (STAI score >or=55)- and
      low (STAI score <or=45)-anxiety groups were selected. A video of corneal surgery
      was served as the stressor for 15 min. Salivary cortisol and amylase levels were
      used as indices of the HPA and SAM activities, respectively. beta-endorphin was
      also assayed as a possible index of HPA activity. There were no differences in
      the resting salivary parameters among the groups. As expected, cortisol and
      amylase levels were significantly increased in all groups after the stressful
      video viewing. There were no gender differences in amylase levels in either the
      high- or low-anxiety groups. However, cortisol levels in highly anxious females
      were significantly lower than those in highly anxious males. Our findings show
      that highly anxious females exhibited lower cortisol release than highly anxious
      males, suggesting that high trait anxiety in females may be associated with an
      inability to respond with sufficient activation of HPA under acute psychological
      stress.

PMID- 17435162
TI  - Small-molecule vasopressin-2 receptor antagonist identified by a g-protein
      coupled receptor "pathway" screen.
AB  - G-protein-coupled receptors (GPCRs) such as the vasopressin-2 receptor (V(2)R)
      are an important class of drug targets. We developed an efficient screen for GPCR
      induced cAMP elevation using as read-out cAMP activation of cystic fibrosis
      transmembrane conductance regulator (CFTR) Cl(-) channels. Fischer rat thyroid
      cells expressing CFTR and a halide-sensing yellow fluorescent protein
      (H148Q/I152L) were transfected with V(2)R. Increased cell Cl(-) conductance after
      agonist-induced cAMP elevation was assayed using a plate reader from cell
      fluorescence after solution I(-) addition. The Z' factor for the assay was
      approximately 0.7 with the V(2)R agonist [deamino-Cys1, Val4, d-Arg8]-vasopressin
      (1 nM) as positive control. Primary screening of 50,000 small molecules yielded a
      novel, 5-aryl-4-benzoyl-3-hydroxy-1-(2-arylethyl)-2H-pyrrol-2-one class of V(2)R
      antagonists that are unrelated structurally to known V(2)R antagonists. The most
      potent compound, V(2)R(inh)-02, which was identified by screening 35 structural
      analogs, competitively inhibited V(2)R-induced cAMP elevation with K(i) value of
      approximately 70 nM and fully displaced radiolabeled vasopressin in binding
      experiments. V(2)R(inh)-02 did not inhibit forskolin or beta(2)-adrenergic
      receptor-induced cAMP production and was more than 50 times more potent for V(2)R
      than for V(1a)R. The favorable in vitro properties of the pyrrol-2-one
      antagonists suggests their potential usefulness in aquaretic applications. The
      CFTR-linked cAMP assay developed here is applicable for efficient, high
      throughput identification of modulators of cAMP-coupled GPCRs.

PMID- 17435163
TI  - A delicate balance of complexation vs. activation of alkanes interacting with
      [Re(Cp)(CO)(PF3)] studied with NMR and time-resolved IR spectroscopy.
AB  - The organometallic alkane complexes Re(Cp)(CO)(PF(3))(alkane) and
      Re(Cp)(CO)(2)(alkane) have been detected after the photolysis of
      Re(Cp)(CO)(2)(PF(3)) in alkane solvent. NMR and time-resolved IR experiments
      reveal that the species produced by the interaction of n-pentane with
      [Re(Cp)(CO)(PF(3))] are an equilibrium mixture of Re(Cp)(CO)(PF(3))(pentane) and
      Re(Cp)(CO)(PF(3))(pentyl)H. The interaction of cyclopentane with
      [Re(Cp)(CO)(PF(3))] most likely results in a similar equilibrium between
      cyclopentyl hydride and cyclopentane complexes. An increasing proportion of
      alkane complex is observed on going from n-pentane to cyclopentane to
      cyclohexane, where only a small amount, if any, of the cyclohexyl hydride form is
      present. In general, when [Re(Cp)(CO)(PF(3))] reacts with alkanes, the products
      display a higher degree of oxidative cleavage in comparison with [Re(Cp)(CO)(2)],
      which favors alkane complexation without activation. Species with the formula
      Re(Cp)(CO)(PF(3))(alkane) have higher thermal stability and lower reactivity
      toward CO than the analogous Re(Cp)(CO)(2)(alkane) complexes.

PMID- 17435164
TI  - C-C sigma complexes of rhodium.
AB  - In this article, the complexes [Rh(Binor-S')(PR3)][BAr(4)(F)] (R = (i)Pr, Cy,
      C(5)H(9)) are described. A combination of x-ray crystallography, NMR
      spectroscopy, density functional theory, and "atoms in molecules" calculations
      unequivocally demonstrates that the complexes contain rare examples of metal...C
      C agostic interactions. Moreover, they are fluxional on the NMR time scale,
      undergoing rapid and reversible C-C activation. Kinetic data and calculations
      point to a bismetallacyclobutane, Rh(V), intermediate.

PMID- 17435165
TI  - Systemic lupus erythematosus-associated defects in the inhibitory receptor
      FcgammaRIIb reduce susceptibility to malaria.
AB  - Polygenic autoimmune diseases, such as systemic lupus erythematosus (SLE), are a
      significant cause of morbidity and mortality worldwide. In recent years,
      functionally important genetic polymorphisms conferring susceptibility to SLE
      have been identified, but the evolutionary pressures driving their retention in
      the gene pool remain elusive. A defunctioning, SLE-associated polymorphism of the
      inhibitory receptor FcgammaRIIb is found at an increased frequency in African and
      Asian populations, broadly corresponding to areas where malaria is endemic. Here,
      we show that FcgammaRIIb-deficient mice have increased clearance of malarial
      parasites (Plasmodium chabaudi chabaudi) and develop less severe disease. In
      vitro, the human lupus associated FcgammaRIIb polymorphism enhances phagocytosis
      of Plasmodium falciparum-infected erythrocytes. These results demonstrate that
      FcgammaRIIb is important in controlling the immune response to malarial parasites
      and suggests that the higher frequency of human FcgammaRIIb polymorphisms
      predisposing to SLE in Asians and Africans may be maintained because these
      variants reduce susceptibility to malaria.

PMID- 17435167
TI  - Conventional wisdom and climate history.

PMID- 17435166
TI  - MHC class II deprivation impairs CD4 T cell motility and responsiveness to
      antigen-bearing dendritic cells in vivo.
AB  - The role continuous contact with self-peptide/MHC molecules (self ligands) in the
      periphery plays in the function of mature T cells remains unclear. Here, we
      elucidate a role for MHC class II molecules in T cell trafficking and antigen
      responsiveness in vivo. We find that naive CD4 T cells deprived of MHC class II
      molecules demonstrate a progressive and profound defect in motility (measured by
      real-time two-photon imaging) and that these cells have a decreased ability to
      interact with limiting numbers of cognate antigen-bearing dendritic cells, but
      they do not demonstrate a defect in their responsiveness to direct stimulation
      with anti-CD3 monoclonal antibody. Using GST fusion proteins, we show that MHC
      class II availability promotes basal activation of Rap1 and Rac1 but does not
      alter the basal activity of Ras. We propose that tonic T cell receptor signaling
      from self-ligand stimulation is required to maintain a basal state of activation
      of small guanosine triphosphatases critical for normal T cell motility and that T
      cell motility is critical for the antigen receptivity of naive CD4 T cells. These
      studies suggest a role for continuous self-ligand stimulation in the periphery
      for the maintenance and function of mature naive CD4 T cells.

PMID- 17435168
TI  - Optimization procedure for small interfering RNA transfection in a 384-well
      format.
AB  - High-throughput screening of RNAi libraries has become an essential part of
      functional analysis in academic and industrial settings. The transition of a cell
      based RNAi assay into a 384-well format requires several optimization steps to
      ensure the phenotype being screened is appropriately measured and that the signal
      to-background ratio is above a certain quantifiable threshold. Methods currently
      used to assess small interfering RNA (siRNA) efficacy after transfection,
      including quantitative PCR or branch DNA analysis, face several technical
      limitations preventing the accurate measurement of mRNA levels in a 384-well
      format. To overcome these difficulties, the authors developed an approach using a
      viral-based transfection system that measures siRNA efficacy in a standardized
      384-well assay. This method allows measurement of siRNA activity in a
      phenotypically neutral manner by quantifying the knockdown of an exogenous
      luciferase gene delivered by a lentiviral vector. In this assay, the efficacy of
      a luciferase siRNA is compared to a negative control siRNA across many distinct
      assay parameters including cell type, cell number, lipid type, lipid volume, time
      of the assay, and concentration of siRNA. Once the siRNA transfection is
      optimized as a 384-well luciferase knockdown, the biologically relevant
      phenotypic analysis can proceed using the best siRNA transfection conditions.
      This approach provides a key technology for 384-well assay development when
      direct measurement of mRNA knockdown is not possible. It also allows for direct
      comparison of siRNA activity across cell lines from almost any mammalian species.
      Defining optimal conditions for siRNA delivery into mammalian cells will greatly
      increase the speed and quality of large-scale siRNA screening campaigns.

PMID- 17435170
TI  - A support vector machine classifier for recognizing mitotic subphases using high
      content screening data.
AB  - High-content screening studies of mitotic checkpoints are important for
      identifying cancer targets and developing novel cancer-specific therapies. A
      crucial step in such a study is to determine the stage of cell cycle. Due to the
      overwhelming number of cells assayed in a high-content screening experiment and
      the multiple factors that need to be taken into consideration for accurate
      determination of mitotic subphases, an automated classifier is necessary. In this
      article, the authors describe in detail a support vector machine (SVM) classifier
      that they have implemented to recognize various mitotic subphases. In contrast to
      previous studies to recognize subcellular patterns, they used only low-resolution
      cell images and a few parameters that can be calculated inexpensively with off
      the-shelf image-processing software. The performance of the SVM was evaluated
      with a cross-validation method and was shown to be comparable to that of a human
      expert.

PMID- 17435169
TI  - High-throughput identification of inhibitors of human mitochondrial peptide
      deformylase.
AB  - The human mitochondrial peptide deformylase (HsPDF) provides a potential new
      target for broadly acting antiproliferative agents. To identify novel
      nonpeptidomimetic and nonhydroxamic acid-based inhibitors of HsPDF, the authors
      have developed a high-throughput screening (HTS) strategy using a fluorescence
      polarization (FP)-based binding assay as the primary assay for screening chemical
      libraries, followed by an enzymatic-based assay to confirm hits, prior to
      characterization of their antiproliferative activity against established tumor
      cell lines. The authors present the results and performance of the established
      strategy tested in a pilot screen of 2880 compounds and the identification of the
      1st inhibitors. Two common scaffolds were identified within the hits.
      Furthermore, cytotoxicity studies revealed that most of the confirmed hits have
      antiproliferative activity. These findings demonstrate that the designed strategy
      can identify novel functional inhibitors and provide a powerful alternative to
      the use of functional assays in HTS and support the hypothesis that HsPDF
      inhibitors may constitute a new class of antiproliferative agent.

PMID- 17435171
TI  - The use of strictly standardized mean difference for hit selection in primary RNA
      interference high-throughput screening experiments.
AB  - RNA interference (RNAi) high-throughput screening (HTS) has been hailed as the
      2nd genomics wave following the 1st genomics wave of gene expression microarrays
      and single-nucleotide polymorphism discovery platforms. Following an RNAi HTS,
      the authors are interested in identifying short interfering RNA (siRNA) hits with
      large inhibition/activation effects. For hit selection, the z-score method and
      its variants are commonly used in primary RNAi HTS experiments. Recently,
      strictly standardized mean difference (SSMD) has been proposed to measure the
      siRNA effect represented by the magnitude of difference between an siRNA and a
      negative reference group. The links between SSMD and d+-probability offer a clear
      interpretation of siRNA effects from a probability perspective. Hence, SSMD can
      be used as a ranking metric for hit selection. In this article, the authors
      investigated both the SSMD-based testing process and the use of SSMD as a ranking
      metric for hit selection in 2 primary siRNA HTS experiments. The analysis results
      showed that, as a ranking metric, SSMD was more stable and reliable than
      percentage inhibition and led to more robust hit selection results. Using the
      SSMD -based testing method, the false-negative rate can more readily be obtained.
      More important, the use of the SSMD-based method can result in a reduction in
      both the false-negative and false-positive rates. The applications presented in
      this article demonstrate that the SSMD method addresses scientific questions and
      fills scientific needs better than both percentage inhibition and the commonly
      used z-score method for hit selection.

PMID- 17435172
TI  - Discovery of selective small-molecule CD80 inhibitors.
AB  - Protein-protein interactions are widely found in biological systems controlling
      diverse cellular events. Because these interactions are implicated in many
      diseases such as autoimmunity and cancer, regulation of protein-protein
      interactions provides ideal targets for drug intervention. The CD80-CD28
      costimulatory pathway plays a critical role in regulation of the immune response
      and thus constitutes an attractive target for therapeutic manipulation of
      autoimmune diseases. The objective of this study is to identify small compounds
      disrupting these pivotal protein-protein interactions. Compounds that
      specifically blocked binding of CD80 to CD28 were identified using a strategy
      involving a cell-based scintillation proximity assay as the initial step.
      Secondary screening (e.g., by analyzing the direct binding of these compounds to
      the target immobilized on a biosensor surface) revealed that these compounds are
      highly selective CD80 binders. Screening of structurally related derivatives led
      to the identification of the chemical features required for inhibition of the
      CD80-CD28 interaction. In addition, the optimization process led to a 10-fold
      increase in binding affinity of the CD80 inhibitors. Using this approach, the
      authors identify low-molecular-weight compounds that specifically and with high
      potency inhibit the interaction between CD80 and CD28. These compounds serve as
      promising starting points for further development of CD80 inhibitors as potential
      immunomodulatory drugs.

PMID- 17435173
TI  - Dipyrone elicits substantial inhibition of peripheral cyclooxygenases in humans:
      new insights into the pharmacology of an old analgesic.
AB  - Dipyrone (INN, metamizol) is a common analgesic used worldwide. Its widespread
      prescription or over-the-counter use in many countries (e.g., Brazil, Israel,
      Mexico, Russia, Spain) requires insight into its mode of action. This study
      therefore addressed the impact of its metabolites 4-methyl-amino-antipyrine (MAA)
      and 4-amino-antipyrine (AA) on peripheral cyclooxygenases (COX). Pharmacokinetics
      of metabolites and ex vivo COX inhibition were assessed in five volunteers
      receiving dipyrone at single oral doses of 500 or 1000 mg. Coagulation-induced
      thromboxane B2 formation and lipopolysaccharide-induced prostaglandin E2
      synthesis were measured in vitro and ex vivo in human whole blood as indices of
      COX-1 and COX-2 activity. In vitro, metabolites elicited no substantial COX-1/COX
      2 selectivity with MAA (IC50=2.55 micromol/L for COX-1; IC50=4.65 micromol/L for
      COX-2), being approximately 8.2- or 9-fold more potent than AA. After
      administration of dipyrone, MAA plasma concentrations remained above the IC50
      values for each isoform for at least 8 h (500 mg) and 12 h (1000 mg) postdose.
      COX inhibition correlated with MAA plasma levels (ex vivo IC50 values of 1.03
      micromol/L [COX-1] and 0.87 micromol/L [COX-2]). By contrast, plasma peak
      concentrations of AA after the 1000 mg dose were 2.8- and 6.5-fold below its IC50
      values for COX-1 and COX-2, respectively. Maximal inhibitions of COX-1 and COX-2
      were 94% and 87% (500 mg), 97% and 94% (1000 mg). Taken together, dipyrone
      elicits a substantial and virtually equipotent inhibition of COX isoforms via
      MAA. Given the profound COX-2 suppression by dipyrone, which was considerably
      above COX-2 inhibition by single analgesic doses of celecoxib and rofecoxib, a
      significant portion of its analgesic action may be ascribed to peripheral
      mechanisms. In view of the observed COX-1 suppression, physicochemical factors
      (lack of acidity) rather than differential COX-1 inhibition may be responsible
      for dipyrone's favorable gastrointestinal tolerability compared with acidic COX
      inhibitors.

PMID- 17435174
TI  - Altered vitamin A homeostasis and increased size and adiposity in the rdh1-null
      mouse.
AB  - Rat RoDH performs efficiently (V(m)/K(m)) in a pathway of all-trans-retinoic acid
      biosynthesis in cells and recognizes the physiological form of vitamin A, i.e.,
      retinol bound with cellular retinol binding-protein, type I. Here we report that
      mouse embryo (e7.5 to e18.5) and liver (e12.5 to P2M) display inversely related
      mRNA expression of an Rodh ortholog, rdh1, and a major retinoic acid catabolic
      enzyme, cyp26a1, suggesting coordinate modulation of retinoic acid homeostasis.
      Rdh1 inactivation by homologous recombination produces mice with decreased liver
      cyp26a1 mRNA and protein and increased liver and kidney retinoid stores, when fed
      vitamin A-restricted diets. Thus, null mice autocompensate by down-regulating
      cyp26a1 and sparing retinoids, indicating that rdh1 metabolizes retinoids in
      vivo. Surprisingly, rdh1-null mice grow longer than wild type, with increased
      weight and adiposity, when restricted in vitamin A. Liver, kidney, and multiple
      fat pads increase in weight. Some differences reflect the larger sizes of rdh1
      null mice, but mesentery, femoral, and inguinal fat pads grow disproportionately
      larger. These data reveal an unexpected contribution of Rdh1 to size and
      adiposity and provide the first genetic evidence of a candidate retinol
      dehydrogenase affecting either vitamin A-related homeostasis physiologically or
      vitamin A-related gene expression or biological function in vivo.

PMID- 17435175
TI  - Regulation of matrix metalloproteinase-2 (MMP-2) activity by phosphorylation.
AB  - The regulation of matrix metalloproteinases (MMP) has been studied extensively
      due to the fundamental roles these zinc-endopeptidases play in diverse
      physiological and pathological processes. However, phosphorylation has not
      previously been considered as a potential modulator of MMP activity. The
      ubiquitously expressed MMP-2 contains 29 potential phosphorylation sites. Mass
      spectrometry reveals that at least five of these sites are phosphorylated in
      hrMMP-2 expressed in mammalian cells. Treatment of HT1080 cells with an activator
      of protein kinase C results in a change in MMP-2 immunoreactivity on 2D
      immunoblots consistent with phosphorylation, and purified MMP-2 is phosphorylated
      by protein kinase C in vitro. Furthermore, MMP-2 from HT1080 cell-conditioned
      medium is immunoreactive with antibodies directed against phosphothreonine and
      phosphoserine, which suggests that it is phosphorylated. Analysis of MMP-2
      activity by zymography, gelatin dequenching assays, and measurement of kinetic
      parameters shows that the phosphorylation status of MMP-2 significantly affects
      its enzymatic properties. Consistent with this, dephosphorylation of MMP-2
      immunoprecipitated from HT1080 conditioned medium with alkaline phosphatase
      significantly increases its activity. We conclude that MMP-2 is modulated by
      phosphorylation on multiple sites and that protein kinase C may be a regulator of
      this protease in vivo.

PMID- 17435176
TI  - The immunophilin FKBP52 specifically binds to tubulin and prevents microtubule
      formation.
AB  - The FK506 binding protein FKBP52 belongs to the large family of immunophilins and
      is known as a steroid receptor-associated protein. Previous data suggest that
      FKBP52 is associated with the motor protein dynein and with the cytoskeleton
      during mitosis. Here we demonstrate a specific and direct interaction between
      FKBP52 and tubulin. The region of FKBP52 located between aa 267 and 400, which
      includes the tetratricopeptide repeat domain, is required for tubulin binding. We
      provide evidence that FKBP52 prevents tubulin polymerization and that an 84
      residue sequence located in the C-terminal part of the molecule (aa 375-458) is
      necessary and sufficient for its microtubule depolymerization activity. In
      colocalization experiments in PC12 cells, FKBP52 is associated with tubulin in
      motile cellular compartments. Furthermore, we suggest that, by using siRNA, a
      decrease of FKBP52 expression in PC12 cells may lead to differentiated cell
      phenotype characterized by neurite extensions. Collectively, our data define an
      unexpected property of FKBP52 as a novel regulator of microtubule dynamics. The
      possible role of microtubule formation and tubulin binding of other immunophilins
      such as FKBP12 and FKBP51 is discussed.

PMID- 17435177
TI  - Endoplasmic reticulum stress increases myofiber formation in vitro.
AB  - Myoblast differentiation involves myoblast fusion followed by myofiber formation.
      We recently demonstrated that endoplasmic reticulum (ER) stress signaling occurs
      during myoblast differentiation in vivo. This signaling results in apoptosis in a
      subpopulation of myoblasts. In a cell culture model of myogenesis, inhibition of
      ER stress signaling blocked apoptosis and myoblast differentiation. To further
      examine the role of ER stress during myogenesis, we exposed cultured myoblasts to
      ER stress inducers during the transition from proliferation to differentiation.
      The stress inducers tunicamycin (an inhibitor of N-glycosylation in the ER) and
      thapsigargin (an inhibitor of ER-specific calcium ATPase) were used at doses that
      induce 40-50% apoptosis in myoblast cultures. Increased ER stress enhanced
      differentiation-associated apoptosis of myoblasts. It is likely that apoptosis
      induced by ER stress selectively eliminates vulnerable cells. We found that the
      surviving myoblast cells were even more resistant to apoptosis. Remarkably, the
      surviving cells efficiently differentiated into contracting myofibers that are
      rarely found in culture models of myogenesis. Our observations suggest that ER
      stress exerts a positive effect on myofiber formation, possibly mimicking the
      action of signals that drive apoptosis and differentiation in vivo. These results
      may provide important insight for developing therapies to improve myofiber
      formation.

PMID- 17435178
TI  - Identification and selection of cardiomyocytes during human embryonic stem cell
      differentiation.
AB  - Human embryonic stem cells (hESC) are pluripotent lines that can differentiate in
      vitro into cell derivatives of all three germ layers, including cardiomyocytes.
      Successful application of these unique cells in the areas of cardiovascular
      research and regenerative medicine has been hampered by difficulties in
      identifying and selecting specific cardiac progenitor cells from the mixed
      population of differentiating cells. We report the generation of stable
      transgenic hESC lines, using lentiviral vectors, and single-cell clones that
      express a reporter gene (eGFP) under the transcriptional control of a cardiac
      specific promoter (the human myosin light chain-2V promoter). Our results
      demonstrate the appearance of eGFP-expressing cells during the differentiation of
      the hESC as embryoid bodies (EBs) that can be identified and sorted using FACS
      (purity>95%, viability>85%). The eGFP-expressing cells were stained positively
      for cardiac-specific proteins (>93%), expressed cardiac-specific genes, displayed
      cardiac-specific action-potentials, and could form stable myocardial cell grafts
      following in vivo cell transplantation. The generation of these transgenic hESC
      lines may be used to identify and study early cardiac precursors for
      developmental studies, to robustly quantify the extent of cardiomyocyte
      differentiation, to label the cells for in vivo grafting, and to allow derivation
      of purified cell populations of cardiomyocytes for future myocardial cell therapy
      strategies.

PMID- 17435180
TI  - Survey of treatment recommendations for anaplastic oligodendroglioma.
AB  - Anaplastic oligodendroglioma is a malignant brain tumor uniquely sensitive to
      treatment with both chemotherapy and radiotherapy. There are few prospective
      clinical trials for newly diagnosed patients and multiple approaches to the
      treatment of these patients. This study explored the recommended treatment
      offered by experts in neuro-oncology. A Web-based survey was developed and
      distributed to 800 members of the Society of Neuro-Oncology (SNO) who had an e
      mail address listed with SNO. Questions addressed use of molecular genetic
      information and treatment recommendations. A total of 99 clinical SNO members
      (20%) responded. The majority reported practicing at an academic center in the
      United States. Two-thirds of respondents see more than five patients with newly
      diagnosed anaplastic oligodendroglioma annually. Molecular genetic testing was
      requested for more than 75% of patients, and the results significantly influenced
      treatment recommendations (p = 0.000003). Regardless of molecular genetic status,
      the most commonly recommended treatment was the use of concurrent temozolomide
      and radiotherapy followed by adjuvant temozolomide (18%-34%). The current survey
      demonstrates that although neuro-oncologists have embraced the use of molecular
      genetic studies in newly diagnosed anaplastic oligodendroglioma, treatment
      recommendations vary widely and are often independent of the molecular data.

PMID- 17435179
TI  - Clinical utility of a patient-specific algorithm for simulating intracerebral
      drug infusions.
AB  - Convection-enhanced delivery (CED) is a novel drug delivery technique that uses
      positive infusion pressure to deliver therapeutic agents directly into the
      interstitial spaces of the brain. Despite the promise of CED, clinical trials
      have demonstrated that target-tissue anatomy and patient-specific physiology play
      a major role in drug distribution using this technique. In this study, we
      retrospectively tested the ability of a software algorithm using MR diffusion
      tensor imaging to predict patient-specific drug distributions by CED. A tumor
      targeted cytotoxin, cintredekin besudotox (interleukin 13-PE38QQR), was coinfused
      with iodine 123-labeled human serum albumin (123I-HSA), in patients with
      recurrent malignant gliomas. The spatial distribution of 123I-HSA was then
      compared to a drug distribution simulation provided by the software algorithm.
      The algorithm had a high sensitivity (71.4%) and specificity (100%) for
      identifying the high proportion (7 of 14) of catheter trajectories that failed to
      deliver drug into the desired anatomical region (p = 0.021). This usually
      occurred when catheter trajectories crossed deep sulci, resulting in leak of the
      infusate into the subarachnoid cerebrospinal fluid space. The mean concordance of
      the volume of distribution at the 50% isodose level between the actual 123I-HSA
      distribution and simulation was 65.75% (95% confidence interval [CI], 52.0%
      79.5%), and the mean maximal inplane deviation was less than 8.5 mm (95% CI, 4.0
      13.0 mm). The use of this simulation algorithm was considered clinically useful
      in 84.6% of catheters. Routine use of this algorithm, and its further
      developments, should improve prospective selection of catheter trajectories, and
      thereby improve the efficacy of drugs delivered by this promising technique.

PMID- 17435181
TI  - Carbonic anhydrase II in the endothelium of glial tumors: a potential target for
      therapy.
AB  - Carbonic anhydrase isozyme II (CA II) is a cytosolic enzyme that is highly
      expressed in most organs, including the brain, where it is mainly located in the
      oligodendrocytes. Recent studies have shown that its expression is induced in the
      endothelium of neovessels in melanoma and esophageal, renal, and lung cancer.
      Immunological studies further indicate that CA II represents a major target
      antigen stimulating an autoantibody response in melanoma patients. These results
      prompted us to investigate endothelial CA II expression in two types of brain
      cancer: oligodendrogliomas and astrocytomas. A series of 255 astrocytoma and 71
      oligodendroglial tumor specimens was immunostained for CA II. The staining
      results were correlated with a number of different clinicopathological factors
      and survival data. CA II showed weak or no expression in low-grade tumors, while
      grade 3 mixed oligoastrocytoma and glioblastoma multiforme were the most
      positively stained tumor types. Survival analysis indicated that endothelial CA
      II staining is significantly associated with a poor prognosis in patients with
      astrocytomas. About 17% of patients with CA II-negative tumors (weak or no
      endothelial signal) were still alive at the end of the follow-up period of five
      years. The presence of CA II in the tumor endothelium suggests that it may play
      an important functional role in tumor metabolism. From a clinical perspective,
      the results also open new avenues for selecting tumor types for dendritic cell
      therapy trials.

PMID- 17435182
TI  - The development of human sera tests for HDL-bound serum PON1 and its
      lipolactonase activity.
AB  - Serum paraoxonase (PON1) is a lipolactonase that associates with HDL
      apolipoprotein A-I (HDL-apoA-I) and thereby plays a role in the prevention of
      atherosclerosis. Current sera tests make use of promiscuous substrates and
      provide no indications regarding HDL-PON1 complex formation. We developed new
      enzymatic tests that detect total PON1 levels, irrespective of HDL status and R/Q
      polymorphism, as well as the degree of catalytic stimulation and increased
      stability that follow PON1's tight binding to HDL-apoA-I. The tests are based on
      measuring total PON1 levels with a fluorogenic phosphotriester, measuring the
      lipolactonase activity with a chromogenic lactone, and assaying the enzyme's
      chelator-mediated inactivation rate. The latter two are affected by tight HDL
      binding and thereby derive the levels of the serum PON1-HDL complex. We
      demonstrate these new tests with a group of healthy individuals (n=54) and show
      that the levels of PON1-HDL vary by a factor of 12. Whereas the traditionally
      applied paraoxonase and arylesterase tests weakly reflect PON1-HDL levels
      (R=0.64), the lipolactonase test provides better correlation (R=0.80). These new
      tests indicate the levels and activity of PON1 in a physiologically relevant
      context as well as the levels and quality of the HDL particles with which the
      enzyme is associated.

PMID- 17435185
TI  - Biot's breathing.

PMID- 17435183
TI  - Notes on the kidney and its diseases for the neurologist.
AB  - To save their patients from dialysis and transplantation, neurologists need
      simply remain alert to the possibility of renal failure, particularly in the
      context of systemic disease, diabetes, sepsis and drugs. Of the numerous
      territories shared by our respective specialities, we outline a pragmatic
      approach to the diagnosis and treatment of the vasculitides, underpinned by
      knowing which questions to ask, equally importantly when to ask them, and in the
      art of obtaining a tissue diagnosis. We consider the current evolving trial
      evidence that directs the usage of a growing arsenal of therapies in the
      induction and maintenance stages of vasculitis treatment, and extend this
      consideration to Lupus and Sjogren's.

PMID- 17435186
TI  - Early epileptic seizures after stroke are associated with increased risk of new
      onset dementia.
AB  - BACKGROUND: Subclinical vascular or degenerative lesions occur in the brain
      before the clinical expression of dementia. Those lesions in a brain that just
      experienced a stroke may have lower thresholds for early epileptic seizures.
      Therefore, epileptic seizures may be a marker of subclinical brain lesions, which
      may lead to dementia. OBJECTIVE: To test the hypothesis that patients with stroke
      who have epileptic seizures without dementia have an increased risk of new-onset
      dementia. METHODS: 169 consecutive patients with stroke without pre-existing
      dementia recruited in the Lille Stroke/Dementia Study were investigated (90 men;
      150 ischaemic strokes; median age 73 years). Pre-stroke cognitive functions were
      evaluated with the Informant Questionnaire on Cognitive Decline in the Elderly
      (IQCODE), with a cut-off of 104 for the diagnosis of dementia. The patients were
      followed up over a 3-year period. Dementia was diagnosed with International
      Classification of Diseases, 10th revision criteria in survivors who underwent
      neurological visits, and with the IQCODE score in those who could not. The
      relationship between epileptic seizures and new-onset dementia was studied within
      3 years, using life-table methods. RESULTS: 9 patients (5.3%; 95% CI 2.9 to 8.7%)
      had early seizures. Epileptic seizures were independent predictors of new-onset
      dementia within 3 years after stroke (HR 3.81; 95% CI 1.13 to 12.82), with
      increasing age (HR 1.04; 95% CI 1.01 to 1.08), IQCODE scores at admission (HR
      1.08; 95% CI 1.02 to 1.13) and diabetes mellitus (HR 3.52; 95% CI 1.46 to 8.47).
      CONCLUSION: Patients with stroke who have epileptic seizures may be at increased
      risk of dementia. Whether cognitive follow-up should be systematically performed
      in those patients remains to be validated.

PMID- 17435187
TI  - Prolonged hemiplegic episodes in children due to mutations in ATP1A2.
AB  - BACKGROUND: Familial hemiplegic migraine (FHM) is an unusual migraine syndrome
      characterised by recurrent transient attacks of unilateral weakness or paralysis
      as part of the migraine aura. Genetically and clinically heterogeneous, FHM1 is
      caused by mutations in CACNA1A and FHM2 by mutations in ATP1A2. AIM: Three
      children with prolonged hemiplegia were tested for mutations in CACNA1A or
      ATP1A2. METHODS: Mutations in CACNA1A and ATP1A2 were screened for by denaturing
      high performance liquid chromatography and confirmed by sequencing. Expression
      studies were performed to characterise the functional consequences of these
      mutations. RESULTS: No mutation was found in the FHM1 gene while three mutations
      were identified in the FHM2 gene. All three mutations were missense: two were
      novel and one was de novo; none was found in controls. Functional studies in HeLa
      cells showed complete loss of mutant pump function without interfering with the
      wild-type pump, consistent with haploinsufficiency. CONCLUSION: We identified
      novel disease causing mutations in the FHM2 gene. Genetic screening for FHM
      should be considered in a child with prolonged hemiplegia even if there is no
      prior history or family history of migraine or hemiplegic episodes.

PMID- 17435188
TI  - Neurological picture. Multiple ring enhancing lesions in brain MRI of a patient
      with AIDS.

PMID- 17435189
TI  - Central compensation of deviated subjective visual vertical in Wallenberg's
      syndrome.
AB  - The central compensation of vestibular tonus imbalance due to unilateral
      peripheral vestibular lesions has been repeatedly documented. Little is known,
      however, about the central compensation of vestibular tonus imbalance due to
      central lesions. Dorsolateral medullary infarctions (Wallenberg's syndrome)
      typically cause a central vestibular tonus imbalance in the roll plane with
      deviations of perceived verticality and ipsiversive body lateropulsion. The
      course of normalisation of the tilts of subjective visual vertical (SVV) in 50
      patients who had acute Wallenberg's syndrome were retrospectively compared with
      that in 50 patients with acute vestibular neuritis. The initial displacement of
      SVV was 9.8 degrees in Wallenberg's syndrome and 7 degrees in vestibular
      neuritis. The deviation of SVV significantly decreased over time within days to
      weeks in both groups. This finding shows that the time courses of the central
      compensation for dorsolateral medullary infarctions and peripheral vestibular
      lesions are similar.

PMID- 17435190
TI  - Maculopapular rash and tremor are associated with West Nile fever and
      neurological syndromes.
AB  - The clinical features associated with West Nile virus (WNV) infections are
      described based on data collected from history forms submitted with samples
      during a province-wide WNV testing programme. Age 40-59 years (OR 1.7, p<0.008),
      residence in the southeast of Alberta (OR 4.2, p<0.001), maculopapular rash (OR
      8.6, p<0.001) or tremor (OR 3.6, p<0.001) were independently associated with WNV
      infection.

PMID- 17435192
TI  - Neurological picture. Armoured brain: case report of a symptomatic calcified
      chronic subdural haematoma.

PMID- 17435191
TI  - Gabapentin in the management of dysautonomia following severe traumatic brain
      injury: a case series.
AB  - The pharmacological management of dysautonomia, otherwise known as autonomic
      storms, following acute neurological insults, is problematic and remains poorly
      researched. This paper presents six subjects with dysautonomia following
      extremely severe traumatic brain injury where gabapentin controlled paroxysmal
      autonomic changes and posturing in the early post-acute phase following limited
      success with conventional medication regimens. In two subjects, other medications
      were reduced or ceased without a recurrence of symptoms. It is proposed that
      medications that can block or minimise abnormal afferent stimuli may represent a
      better option for dysautonomia management than drugs which increase inhibition of
      efferent pathways. Potential mechanisms for these effects are discussed.

PMID- 17435193
TI  - Tourette syndrome and dystonia.

PMID- 17435194
TI  - Hemimacropsia after medial temporo-occipital infarction.

PMID- 17435195
TI  - Guillain-Barre syndrome with antibodies to GD1a/GD1b complex.

PMID- 17435196
TI  - Improvement in neuroleptic-induced akathisia with intravenous iron treatment in a
      patient with iron deficiency.

PMID- 17435197
TI  - Putaminal petechial haemorrhage as the cause of non-ketotic hyperglycaemic
      chorea: a neuropathological case correlated with MRI findings.

PMID- 17435198
TI  - The myopia of governments contributes to maternal mortality: dying from
      socioeconomic and physical distances.

PMID- 17435199
TI  - Endocrine disruption.

PMID- 17435200
TI  - From poor law society to the welfare state: school meals in Norway 1890s-1950s.
AB  - This article examines the main trends in the history of publicly organised school
      meals in Norway, while casting comparative glances at Britain. First, it argues
      that the status of school meals today is strongly influenced by three intertwined
      strains of past tradition: poor relief, universal welfare and the ideal of full
      time and nutritionally competent housewives. Second, tradition is also visible in
      the extent to which publicly organised meals are seen as solutions to problems -
      in the past to hunger or malnourishment, today to obesity and malnourishment -
      and not simply as a meal. Third, the creation of civil and health conscious
      citizens has, to varying degrees, been a part of the school meals programme, as
      the school itself has had, and continues to have, such an agenda.

PMID- 17435201
TI  - Cognitive epidemiology.
AB  - This glossary provides a guide to some concepts, findings and issues of
      discussion in the new field of research in which intelligence test scores are
      associated with mortality and morbidity. Intelligence tests are devised and
      studied by differential psychologists. Some of the major concepts in differential
      psychology are explained, especially those regarding cognitive ability testing.
      Some aspects of IQ (intelligence) tests are described and some of the major tests
      are outlined. A short guide is given to the main statistical techniques used by
      differential psychologists in the study of human mental abilities. There is a
      discussion of common epidemiological concepts in the context of cognitive
      epidemiology.

PMID- 17435202
TI  - Mumps and the media: changes in the reporting of mumps in response to newspaper
      coverage.
AB  - OBJECTIVE: To determine the links between national newspaper coverage of mumps
      after a press release and increased reports of clinical mumps cases. DESIGN AND
      SETTING: A cross sectional study involving people aged 15-24 years in the West
      Midlands, and England and Wales. Reported mumps cases were obtained from
      statutory notifications of infectious diseases to the Health Protection Agency
      and reports to the Royal College of General Practitioners Weekly Returns Service.
      Data on newspaper coverage was obtained by retrospectively reviewing the Health
      Protection Agency press archives. MAIN OUTCOME MEASURE: The effect of newspaper
      coverage was assessed by examining the 4 weeks before the press release (weeks 15
      18 of the year), a 2-week period that included the week of the press release
      (weeks 19-20) and 4 weeks after the press release (weeks 21-24). MAIN RESULTS:
      Mumps notification rates were declining before increased newspaper coverage.
      Significant increases in national (from 28.3/100 000 population (95% CI 26.5 to
      30.1) in weeks 18 to 42.8 (95% CI 40.6 to 45) in week 20) and local (from 9.8
      (95% CI 7.4 to 12.1) to 21.2 (95% CI 17.7 to 24.6)) notification rates were seen
      after increased newspaper coverage. Reports rapidly declined after decreased
      media interest. CONCLUSIONS: The reported incidence rate of mumps seems to be
      markedly influenced by the level of newspaper coverage. This has implications for
      surveillance activities.

PMID- 17435203
TI  - Don Quixotech in New Laputa.

PMID- 17435204
TI  - Mutual interaction between nutritional status and chronic arsenic toxicity due to
      groundwater contamination in an area of Terai, lowland Nepal.
AB  - OBJECTIVE: To reveal the inter-relationship between nutritional status and
      arsenic toxicity. DESIGN: Cross-sectional study. SETTING: A survey in an area of
      lowland Nepal, where a high prevalence of both skin manifestation and
      malnutrition was observed. Daily arsenic intake was estimated by measuring the
      arsenic concentration and daily consumption of the drinking water. PARTICIPANTS:
      Adult villagers (248 men and 291 women). About half were classified as
      "underweight" (body mass index <18.5), indicating poor nutritional status. MAIN
      RESULTS: Arsenic intake was negatively correlated with body mass index and
      substantially increased the prevalence of underweight individuals, among whom the
      prevalence of skin manifestations was 1.65-fold higher than normal weight
      individuals. When exposure level was considered, the prevalence of skin symptoms
      was consistently higher in the underweight than in the normal group. Although
      enhanced susceptibility in men was apparent by the increased prevalence of
      cutaneous symptoms, no sex difference was observed in the prevalence of
      underweight individuals related with exposure to arsenic. CONCLUSIONS: The
      present data suggested that exposure to arsenic is associated with an increased
      prevalence of underweight, a serious health problem in developing countries,
      which in turn is associated with increased skin manifestation of arsenic
      poisoning.

PMID- 17435205
TI  - Air pollution from biomass burning and asthma hospital admissions in a sugar cane
      plantation area in Brazil.
AB  - OBJECTIVE: To evaluate the association between the total suspended particles
      (TSPs) generated from preharvest sugar cane burning and hospital admission due to
      asthma (asthma hospital admissions) in the city of Araraquara. DESIGN: An
      ecological time-series study. Total daily records of asthma hospital admissions
      (ICD 10th J15) were obtained from one of the main hospitals in Araraquara, Sao
      Paulo State, Brazil, from 23 March 2003 to 27 July 2004. The daily concentration
      of TSP (microg/m(3)) was obtained using Handi-vol equipment (Energetica, Brazil)
      placed in downtown Araraquara. The local airport provided the daily mean figures
      of temperature and humidity. The daily number of asthma hospital admissions was
      considered as the dependent variable in Poisson's regression models and the daily
      concentration of TSP was considered the independent variable. The generalised
      linear model with natural cubic spline was adopted to control for long-time
      trend. Linear terms were used for weather variables. RESULTS: TSP had an acute
      effect on asthma admissions, starting 1 day after TSP concentrations increased
      and remaining almost unchanged for the next four days. A 10 microg/m(3) increase
      in the 5-day moving average (lag1-5) of TSP concentrations was associated with an
      increase of 11.6% (95% CI 5.4 to 17.7) in asthma hospital admissions. CONCLUSION:
      Increases in TSP concentrations were definitely associated with asthma hospital
      admissions in Araraquara and, despite using sugar cane alcohol to reduce air
      pollution from automotive sources in large Brazilian urban centres, the cities
      where sugar cane is harvested pay a high toll in terms of public health.

PMID- 17435206
TI  - Educational differences in mobility: the contribution of physical workload,
      obesity, smoking and chronic conditions.
AB  - BACKGROUND: In earlier studies, determinants of socioeconomic gradient in
      mobility have not been measured comprehensively. AIM: To assess the contribution
      of chronic morbidity, obesity, smoking and physical workload to inequalities in
      mobility. METHODS: This was a cross-sectional study on 2572 persons (76% of a
      nationally representative sample of the Finnish population aged > or = 55 years).
      Mobility limitations were measured by self-reports and performance rates.
      RESULTS: According to a wide array of self-reported and test-based indicators,
      persons with a lower level of education showed more mobility limitations than
      those with a higher level. The age-adjusted ORs for limitations in stair climbing
      were threefold in the lowest-educational category compared with the highest one
      (OR 3.3 in men and 2.9 in women for self-reported limitations, and 3.5 in men and
      2.2 in women for test-based limitations). When obesity, smoking, work-related
      physical loading and clinically diagnosed chronic diseases were simultaneously
      accounted for, the educational differences in stair-climbing limitations vanished
      or were greatly diminished. In women, obesity contributed most to the
      differences, followed by a history of physically strenuous work, knee and hip
      osteoarthritis and cardiovascular diseases. In men, diabetes, work-related
      physical loading, musculoskeletal diseases, obesity and smoking contributed
      substantially to the inequalities. CONCLUSIONS: Great educational inequalities
      exist in various measures of mobility. Common chronic diseases, obesity, smoking
      and workload appeared to be the main pathways from low education to mobility
      limitations. General health promotion using methods that also yield good results
      in the lowest-educational groups is thus a good strategy to reduce the
      disparities in mobility.

PMID- 17435207
TI  - Perceived discrimination, socioeconomic disadvantage and refraining from seeking
      medical treatment in Sweden.
AB  - STUDY OBJECTIVE: To analyse the association between perceived discrimination and
      refraining from seeking required medical treatment and the contribution of
      socioeconomic disadvantage. DESIGN AND SETTING: Data from the Swedish National
      Survey of Public Health 2004 were used for analysis. Respondents were asked
      whether they had refrained from seeking required medical treatment during the
      past 3 months. Perceived discrimination was based on whether respondents reported
      that they had been treated in a way that made them feel humiliated (due to
      ethnicity/race, religion, gender, sexual orientation, age or disability). The
      Socioeconomic Disadvantage Index (SDI) was developed to measure economic
      deprivation (social welfare beneficiary, being unemployed, financial crisis and
      lack of cash reserves). PARTICIPANTS: Swedish population-based survey of 14,736
      men and 17,115 women. MAIN RESULTS: Both perceived discrimination and
      socioeconomic disadvantage were independently associated with refraining from
      seeking medical treatment. Experiences of frequent discrimination even without
      any socioeconomic disadvantage were associated with three to nine-fold increased
      odds for refraining from seeking medical treatment. A combination of both
      frequent discrimination and severe SDI was associated with a multiplicative
      effect on refraining from seeking medical treatment, but this effect was
      statistically more conclusive among women (OR = 11.6, 95% CI 8.1 to 16.6; Synergy
      Index (SI) = 2.0 (95% CI 1.2 to 3.2)) than among men (OR = 12, 95% CI 7.7 to
      18.7; SI = 1.6 (95% CI 1.3 to 2.1)). CONCLUSIONS: The goal of equitable access to
      healthcare services cannot be achieved without public health strategies that
      confront and tackle discrimination in society and specifically in the healthcare
      setting.

PMID- 17435208
TI  - Patient cost sharing and physician visits by socioeconomic position: findings in
      three Western European countries.
AB  - The association between educational level and the probability of physician visits
      in three Western European countries, one of which has a system of patient cost
      sharing was evaluated. Cross-sectional surveys were performed in France, Germany
      and Spain around 1990 and around 2000. People representative of the French,
      German and Spanish populations, aged 25-74 years were studied. The probability of
      physician visits decreased in the second period with respect to the first in
      France and Germany, but it increased in Spain. In the two periods studied,
      subjects with low educational level had a lower probability of physician visits
      than those with high educational level in France, in contrast with the general
      trend in Germany and Spain. In both periods, France had patient cost sharing
      whereas Germany and Spain did not. The existence of patient cost sharing in the
      healthcare systems of Western European countries raises doubts about the
      possibility of making use of health services independent of individual
      socioeconomic position.

PMID- 17435209
TI  - What are the effects of anti-discriminatory legislation on socioeconomic
      inequalities in the employment consequences of ill health and disability?
AB  - OBJECTIVE: To investigate how anti-discrimination legislation in the form of the
      UK Disability Discrimination Act (DDA) affected socioeconomic disparities in the
      employment rates of people with a limiting long-term illness (LLTI) or
      disability. DESIGN: National cross-sectional data on employment rates for people
      with and without an LLTI or disability were obtained from the General Household
      Survey (GHS) for a 14-year period (1990-2003; 12 surveys). Representative
      population samples were analysed. The sample size for the GHS over the study
      period ranged from 19,193 to 24,657 and the average response rate ranged from 72%
      to 82%. MAIN OUTCOME MEASURE: Age-standardised employment rates for individuals
      with and without an LLTI or disability, analysed by sex and socioeconomic status.
      RESULTS: Analysis of covariance identified that the DDA had had a negative effect
      on employment rates for individuals with an LLTI or disability during the study
      period. This negative effect was found to be differential according to social
      class ranging from no effect in social classes I and II (-2.86%, 95% CI -8.7% to
      2.99%), increasing with social class group, to a highly significant effect in
      social classes IV and V (-10.7%, 95% CI -6.16% to -15.24%). No differential
      effect was identified by sex. CONCLUSIONS: Anti-discriminatory legislation is not
      an effective way of overcoming the employment consequences of ill health and
      disability, nor is it a useful public policy tool in terms of reducing
      inequalities.

PMID- 17435210
TI  - Organisational justice and smoking: the Finnish Public Sector Study.
AB  - OBJECTIVE: To examine the extent to which the justice of decision-making
      procedures and interpersonal relationships is associated with smoking. SETTING:
      10 municipalities and 21 hospitals in Finland. DESIGN AND PARTICIPANTS: Cross
      sectional data derived from the Finnish Public Sector Study were analysed with
      logistic regression analysis models with generalised estimating equations.
      Analyses of smoking status were based on data provided by 34,021 employees.
      Separate models for heavy smoking (> or = 20 cigarettes/day) were calculated for
      6295 current smokers. RESULTS: After adjustment for age, education, socioeconomic
      position, marital status, job contract and negative affectivity, smokers who
      reported low procedural justice were about 1.4 times more likely to smoke > or =
      20 cigarettes/day compared with their counterparts who reported high levels of
      justice. In a similar way, after adjustments, low levels of justice in
      interpersonal treatment was significantly associated with an increased prevalence
      of heavy smoking (OR 1.35, 95% CI 1.03 to 1.77 for men and OR 1.41, 95% CI 1.09
      to 1.83 for women). Further adjustment for job strain and effort-reward imbalance
      had little effect on these results. No associations were observed between justice
      components and smoking status or ex-smoking. CONCLUSIONS: The extent to which
      employees are treated with justice in the workplace seems to be associated with
      smoking intensity independently of established stressors at work.

PMID- 17435211
TI  - Reproducibility measures and their effect on diet-cancer associations in the Boyd
      Orr cohort.
AB  - OBJECTIVES: To quantify measurement error in the estimation of family diet
      intakes using 7-day household food inventories and to investigate the effect of
      measurement-error adjustment on diet-disease associations. DESIGN AND SETTING:
      Historical cohort study in 16 districts in England and Scotland, between 1937 and
      1939. SUBJECTS: 4999 children from 1352 families in the Carnegie Survey of Diet
      and Health. 86.6% of these children were traced as adults and form the Boyd Orr
      cohort. The reproducibility analysis was based on 195 families with two
      assessments of family diet recorded 3-15 months apart. METHODS: Intraclass
      correlation coefficients (ICCs) were calculated for a variety of nutrients and
      food groups. Diet-cancer associations reported previously in the Boyd Orr cohort
      were reassessed using two methods: (a) the ICC and (b) the regression
      calibration. MAIN RESULTS: The ICCs for the dietary intakes ranged from 0.44
      (beta carotene) to 0.85 (milk and milk products). The crude fully adjusted hazard
      ratio (HR) for cancer mortality per 1 MJ/day increase in energy intake was 1.15
      (95% CI 1.06 to 1.24). After adjustment using the ICC for energy (0.80) the HR
      (95% CI) increased to 1.19 (1.08 to 1.31), and the estimate from regression
      calibration was 1.14 (0.98 to 1.32). The crude fully adjusted odds ratio (OR) for
      cancer incidence per 40 g/day increase in fruit intake was 0.84 (95% CI 0.73 to
      0.97). After adjustment using the fruit ICC (0.78) it became 0.81 (0.67 to 0.96)
      and the OR derived from regression calibration was 0.81 (0.59 to 1.10).
      CONCLUSIONS: The diet-disease relationships for the dietary intakes with low
      measurement error were robust to adjustment for measurement error.

PMID- 17435212
TI  - Alcohol intake and cardiovascular disease and mortality: the role of pre-existing
      disease.
AB  - OBJECTIVES: Pre-existing conditions have been postulated as possible causes of
      the J-shaped relationship between alcohol intake and cardiovascular disease. Two
      research questions have been addressed in this paper. First, whether never
      drinkers and former drinkers differ from moderate drinkers in terms of health,
      and if so, which health problems contribute to this difference. Second, whether
      the U-shaped relationship between current alcohol intake and cardiovascular
      disease or all-cause mortality could in part be explained by difference in pre
      existing disease burden. DESIGN, SETTING AND PARTICIPANTS: A prospective case
      cohort, the Lifestyle and Health Study, consisting of 16,210 men and women aged
      between 45 and 70 years. Alcohol intake and risk factors were assessed at
      baseline with a self-administered questionnaire. Medical information was obtained
      from general practitioners. Cardiovascular events and mortality were followed for
      a period of 5 years (1996-2001). MAIN RESULTS: Never drinkers and former drinkers
      were less healthy than moderate drinkers. They rated their health more often as
      poor, and often had more diseases, such as cardiovascular disease, diabetes, and
      also alcohol-related diseases. The difference in disease burden did not change
      the observed relationship between alcohol intake and cardiovascular events, and
      only partially changed the U-shaped relationship between alcohol intake and all
      cause mortality. CONCLUSIONS: The found difference in health between never
      drinkers and former drinkers compared with moderate drinkers appeared to be only
      a partial explanation of the observed relationships between alcohol intake and
      cardiovascular disease, and between alcohol intake and all-cause mortality.

PMID- 17435213
TI  - Changes in income in the years before death: a record linkage study in Stockholm
      County.

PMID- 17435214
TI  - Non-participation and mortality in different socioeconomic groups: the FINRISK
      population surveys in 1972-92.
AB  - BACKGROUND: Declining response rates pose a serious threat to the validity of
      estimates derived from epidemiological studies. If respondents and non
      respondents differ systematically from each other, there can be a bias in the
      results of the study. A population-based cohort study was conducted to
      investigate disparities in socioeconomic structure between respondents and non
      respondents and the contribution of these disparities to socioeconomic
      differences in total and cardiovascular mortality. DESIGN: Data comprised 32,354
      male and female participants and 4890 non-participants aged 35-74 years who
      belonged to the sample in one of the five FINRISK surveys in 1972, 1977, 1982,
      1987 or 1992 in Finland. They were followed up for 9 years and 6 months. RESULTS:
      It was found that the lower socioeconomic groups were over-represented among non
      respondents both in men and women. When comparing the relative risk of death
      using the highest socioeconomic group of the participants as the reference group,
      it was found that although the socioeconomic gradient was similar for
      participants and non-participants-that is, lower groups had a higher risk of
      death-the risk was at a higher level among non-respondents. CONCLUSIONS: Basing
      analysis on participants does not distort the relative risk of death associated
      with socioeconomic position. However, it does underestimate the absolute risk.

PMID- 17435215
TI  - Effect of conjugal bereavement on mortality of the bereaved spouse in
      participants of the Renfrew/Paisley Study.
AB  - OBJECTIVES: To investigate how loss of a spouse affects mortality risk in the
      bereaved partner. DESIGN AND SETTING: Prospective cohort study in Renfrew and
      Paisley in Scotland. PARTICIPANTS: 4395 married couples aged 45-64 years when the
      study was carried out between 1972 and 1976. METHODS: The date of bereavement for
      the bereaved spouse was the date of death of his or her spouse. Bereavement could
      occur at any time during the follow-up period, so it was considered as a time
      dependent exposure variable and the Cox proportional hazards model for time
      dependent variables was used. The relative rate (RR) of mortality was calculated
      for bereaved versus non-bereaved spouses and adjusted for confounding variables.
      MAIN OUTCOME MEASURES: Causes of death to 31 March 2004. RESULTS: Bereaved
      participants were at higher risk than non-bereaved participants of dying from any
      cause (RR 1.27; 95% CI 1.2 to 1.35). These risks remained but were attenuated
      after adjustment for confounding variables. There were raised RRs for bereaved
      participants dying of cardiovascular disease, coronary heart disease, stroke, all
      cancer, lung cancer, smoking-related cancer, and accidents or violence. After
      adjustment for confounding variables, RRs remained higher for bereaved
      participants for all these causes except for mortality from lung cancer. There
      was no strong statistical evidence that the increased risks of death associated
      with bereavement changed with time after bereavement. CONCLUSIONS: Conjugal
      bereavement, in addition to existing risk factors, is related to mortality risk
      for major causes of death.

PMID- 17435216
TI  - Avoiding bias from aggregate measures of exposure.
AB  - BACKGROUND: Sometimes in descriptive epidemiology or in the evaluation of a
      health intervention policy change, proportions exposed to a risk factor or to an
      intervention are used as explanatory variables in log-linear regressions for
      disease incidence or mortality. AIM: To demonstrate how estimates from such
      models can be substantially inaccurate as estimates of the effect of the risk
      factor or intervention at individual level. To show how the individual level
      effect can be correctly estimated by excess relative risk models. METHODS: The
      problem and solution are demonstrated using data on prostate-specific antigen
      testing and prostate cancer incidence.

PMID- 17435217
TI  - Association of the tensin N-terminal protein-tyrosine phosphatase domain with the
      alpha isoform of protein phosphatase-1 in focal adhesions.
AB  - Focal adhesions attach cultured cells to the extracellular matrix, and we found
      endogenous protein phosphatase-1alpha isoform (PP1alpha) localized in adhesions
      across the entire area of adherent fibroblasts. However, in fibroblasts migrating
      into a scrape wound or spreading after replating PP1alpha did not appear in
      adhesions near the leading edge but was recruited into other adhesions coincident
      in time and space with incorporation of tensin. Endogenous tensin and PP1alpha co
      precipitated from cell lysates with isoform-specific PP1 antibodies. Chemical
      cross-linking of focal adhesion preparations with Lomant's reagent demonstrated
      molecular proximity of endogenous PP1alpha and tensin, whereas neither focal
      adhesion kinase nor vinculin was cross-linked and co-precipitated with PP1alpha,
      suggesting distinct spatial subdomains within adhesions. Transient expression of
      truncated tensin showed the N-terminal 360 residues, which comprise a protein
      tyrosine phosphatase domain, alone were sufficient for isoform-selective co
      precipitation of co-expressed PP1alpha. Human prostate cancer PC3 cells are
      deficient in tensin relative to fibroblasts and have fewer, mostly peripheral
      adhesions. Transient expression of green fluorescent protein tensin in these
      cancer cells induced formation of adhesions and recruited endogenous PP1alpha
      into those adhesions. Thus, the protein-tyrosine phosphatase domain of tensin
      exhibits isoform-specific association with PP1alpha in a restricted spatial
      region of adhesions that are formed during cell migration.

PMID- 17435218
TI  - Nox1 redox signaling mediates oncogenic Ras-induced disruption of stress fibers
      and focal adhesions by down-regulating Rho.
AB  - Generation of reactive oxygen species (ROS) by Ras oncogene-induced NADPH oxidase
      (Nox) 1 is required for Ras transformation phenotypes including anchorage
      independent growth, morphological transformation, and tumorigenesity, but the
      signaling mechanism downstream of Nox1 remains elusive. Rho is known to be a
      critical regulator of actin stress fiber formation. Nonetheless, Rho was reported
      to no longer couple to loss of actin stress fibers in Ras-transformed Swiss3T3
      cells despite the elevation of Rho activity. In this study, however, we
      demonstrate that Rho is inactivated in K-Ras-transformed normal rat kidney cells,
      and that abrogation of Nox1-generated ROS by Nox1 small interference RNAs or
      diphenyleneiodonium restores Rho activation, suggesting that Nox1-generated
      oxidants mediate down-regulation of the Rho activity. This down-regulation
      involves oxidative inactivation of the low molecular weight protein-tyrosine
      phosphatase by Nox1-generated ROS and a subsequent elevation in the tyrosine
      phosphorylated active form of p190RhoGAP, the direct target of the phosphatase.
      Furthermore, the decreased Rho activity leads to disruption of both actin stress
      fibers and focal adhesions in Ras-transformed cells. As for Rac1, Rac1 also
      appears to participate in the down-regulation of Rho via Nox1. Our discovery
      defines a mediating role of Nox1-redox signaling for Ras oncogene-induced actin
      cytoskeletal changes.

PMID- 17435219
TI  - Identification of Mom7, a novel modifier of Apc(Min/+) on mouse chromosome 18.
AB  - The Apc(Min) mouse model of colorectal cancer provides a discrete, quantitative
      measurement of tumor multiplicity, allowing for robust quantitative trait locus
      analysis. This advantage has previously been used to uncover polymorphic
      modifiers of the Min phenotype: Mom1, which is partly explained by Pla2g2a; Mom2,
      a spontaneous mutant modifier; and Mom3, which was discovered in an outbred
      cross. Here, we describe the localization of a novel modifier, Mom7, to the
      pericentromeric region of chromosome 18. Mom7 was mapped in crosses involving
      four inbred strains: C57BL/6J (B6), BTBR/Pas (BTBR), AKR/J (AKR), and A/J. There
      are at least two distinct alleles of Mom7: the recessive, enhancing BTBR, AKR,
      and A/J alleles and the dominant, suppressive B6 allele. Homozygosity for the
      enhancing alleles increases tumor number by approximately threefold in the small
      intestine on both inbred and F(1) backgrounds. Congenic line analysis has
      narrowed the Mom7 region to within 7.4 Mb of the centromere, 28 Mb proximal to
      Apc. Analysis of SNP data from various genotyping projects suggests that the
      region could be as small as 4.4 Mb and that there may be five or more alleles of
      Mom7 segregating among the many strains of inbred mice. This has implications for
      experiments involving Apc(Min) and comparisons between different or mixed genetic
      backgrounds.

PMID- 17435221
TI  - The bursicon gene in mosquitoes: an unusual example of mRNA trans-splicing.
AB  - The bursicon gene in Anopheles gambiae is encoded by two loci. Burs124 on
      chromosome arm 2L contains exons 1, 2, and 4, while burs3 on arm 2R contains exon
      3. Exon 3 is efficiently spliced into position in the mature transcript. This
      unusual gene arrangement is ancient within mosquitoes, being shared by Aedes
      aegypti and Culex pipiens.

PMID- 17435220
TI  - A novel nonnull ZIP1 allele triggers meiotic arrest with synapsed chromosomes in
      Saccharomyces cerevisiae.
AB  - During meiotic prophase, assembly of the synaptonemal complex (SC) brings
      homologous chromosomes into close apposition along their lengths. The Zip1
      protein is a major building block of the SC in Saccharomyces cerevisiae. In the
      absence of Zip1, SC fails to form, cells arrest or delay in meiotic prophase
      (depending on strain background), and crossing over is reduced. We created a
      novel allele of ZIP1, zip1-4LA, in which four leucine residues in the central
      coiled-coil domain have been replaced by alanines. In the zip1-4LA mutant,
      apparently normal SC assembles with wild-type kinetics; however, crossing over is
      delayed and decreased compared to wild type. The zip1-4LA mutant undergoes strong
      checkpoint-induced arrest in meiotic prophase; the defect in cell cycle
      progression is even more severe than that of the zip1 null mutant. When the zip1
      4LA mutation is combined with the pch2 checkpoint mutation, cells sporulate with
      wild-type efficiency and crossing over occurs at wild-type levels. This result
      suggests that the zip1-4LA defect in recombination is an indirect consequence of
      cell cycle arrest. Previous studies have suggested that the Pch2 protein acts in
      a checkpoint pathway that monitors chromosome synapsis. We hypothesize that the
      zip1-4LA mutant assembles aberrant SC that triggers the synapsis checkpoint.

PMID- 17435222
TI  - Wavelet-based parametric functional mapping of developmental trajectories with
      high-dimensional data.
AB  - The biological and statistical advantages of functional mapping result from joint
      modeling of the mean-covariance structures for developmental trajectories of a
      complex trait measured at a series of time points. While an increased number of
      time points can better describe the dynamic pattern of trait development,
      significant difficulties in performing functional mapping arise from prohibitive
      computational times required as well as from modeling the structure of a high
      dimensional covariance matrix. In this article, we develop a statistical model
      for functional mapping of quantitative trait loci (QTL) that govern the
      developmental process of a quantitative trait on the basis of wavelet dimension
      reduction. By breaking an original signal down into a spectrum by taking its
      averages (smooth coefficients) and differences (detail coefficients), we used the
      discrete Haar wavelet shrinkage technique to transform an inherently high
      dimensional biological problem into its tractable low-dimensional representation
      within the framework of functional mapping constructed by a Gaussian mixture
      model. Unlike conventional nonparametric modeling of wavelet shrinkage, we
      incorporate mathematical aspects of developmental trajectories into the smooth
      coefficients used for QTL mapping, thus preserving the biological relevance of
      functional mapping in formulating a number of hypothesis tests at the interplay
      between gene actions/interactions and developmental patterns for complex
      phenotypes. This wavelet-based parametric functional mapping has been
      statistically examined and compared with full-dimensional functional mapping
      through simulation studies. It holds great promise as a powerful statistical tool
      to unravel the genetic machinery of developmental trajectories with large-scale
      high-dimensional data.

PMID- 17435223
TI  - Yct1p, a novel, high-affinity, cysteine-specific transporter from the yeast
      Saccharomyces cerevisiae.
AB  - Cysteine transport in the yeast Saccharomyces cerevisiae is mediated by at least
      eight different permeases, none of which are specific for cysteine. We describe a
      novel, high-affinity, (K(m) = 55 microM), cysteine-specific transporter encoded
      by the ORF YLL055w that was initially identified by a combined strategy of data
      mining, bioinformatics, and genetic analysis. Null mutants of YLL055w, but not of
      the other genes encoding for transporters that mediate cysteine uptake such as
      GAP1, GNP1, MUP1, or AGP1 in a met15Delta background, resulted in a growth defect
      when cysteine, at low concentrations, was provided as the sole sulfur source.
      Transport experiments further revealed that Yll055wp was the major contributor to
      cysteine transport under these conditions. The contributions of the other
      transporters became relevant only at higher concentrations of cysteine or when
      YLL055w was either deleted or repressed. YLL055w expression was repressed by
      organic sulfur sources and was mediated by the Met4p-dependent sulfur regulatory
      network. The results reveal that YLL055w encodes the principal cysteine
      transporter in S. cerevisiae, which we have named YCT1 (yeast cysteine
      transporter). Interestingly, Yct1p belongs to the Dal5p family of transporters
      rather than the amino acid permease family to which all the known amino acid
      transporters belong.

PMID- 17435224
TI  - Joint estimates of quantitative trait locus effect and frequency using synthetic
      recombinant populations of Drosophila melanogaster.
AB  - We develop and implement a strategy to map QTL in two synthetic populations of
      Drosophila melanogaster each initiated with eight inbred founder strains. These
      recombinant populations allow simultaneous estimates of QTL location, effect, and
      frequency. Five X-linked QTL influencing bristle number were resolved to
      intervals of approximately 1.3 cM. We confirm previous observations of bristle
      number QTL distal to 4A at the tip of the chromosome and identify two novel QTL
      in 7F-8C, an interval that does not include any classic bristle number candidate
      genes. If QTL at the tip of the X are biallelic they appear to be intermediate in
      frequency, although there is evidence that these QTL may reside in multiallelic
      haplotypes. Conversely, the two QTL mapping to the middle of the X chromosome are
      likely rare: in each case the minor allele is observed in only 1 of the 16
      founders. Assuming additivity and biallelism we estimate that identified QTL
      contribute 1.0 and 8.7%, respectively, to total phenotypic variation in male
      abdominal and sternopleural bristle number in nature. Models that seek to explain
      the maintenance of genetic variation make different predictions about the
      population frequency of QTL alleles. Thus, mapping QTL in eight-way recombinant
      populations can distinguish between these models.

PMID- 17435225
TI  - No evidence for absence of paternal mtDNA in male progeny from pair matings of
      the mussel Mytilus galloprovincialis.
AB  - The claim that a Mytilus galloprovincialis male failed to transmit mtDNA to its
      sons in controlled crosses is shown to be false. At present there is no evidence
      for mussel males lacking a paternal mtDNA. This makes unlikely the hypothesis
      that maternal genomes may become paternally transmitted by invading the germ line
      of males that lack a paternal genome.

PMID- 17435226
TI  - The early developmental gene Semaphorin 5c contributes to olfactory behavior in
      adult Drosophila.
AB  - Behaviors are complex traits influenced by multiple pleiotropic genes.
      Understanding the mechanisms that give rise to complex behaviors requires an
      understanding of how variation in transcriptional regulation shapes nervous
      system development and how variation in brain structure influences an organism's
      ability to respond to its environment. To begin to address this problem, we used
      olfactory behavior in Drosophila melanogaster as a model and showed that a
      hypomorphic transposon-mediated mutation of the early developmental gene
      Semaphorin-5c (Sema-5c) results in aberrant behavioral responses to the repellant
      odorant benzaldehyde. We fine mapped this effect to the Sema-5c locus using
      deficiency mapping, phenotypic reversion through P-element excision, and
      transgenic rescue. Morphometric analysis of this Sema-5c allele reveals subtle
      neuroanatomical changes in the brain with a reduction in the size of the
      ellipsoid body. High-density oligonucleotide expression microarrays identified 50
      probe sets with altered transcriptional regulation in the Sema-5c background and
      quantitative complementation tests identified epistatic interactions between nine
      of these coregulated genes and the transposon-disrupted Sema-5c gene. Our results
      demonstrate how hypomorphic mutation of an early developmental gene results in
      genomewide transcriptional consequences and alterations in brain structure
      accompanied by profound impairment of adult behavior.

PMID- 17435227
TI  - Ancestry influences the fate of duplicated genes millions of years after
      polyploidization of clawed frogs (Xenopus).
AB  - Allopolyploid species form through the fusion of two differentiated genomes and,
      in the earliest stages of their evolution, essentially all genes in the nucleus
      are duplicated. Because unique mutations occur in each ancestor prior to
      allopolyploidization, duplicate genes in these species potentially are not
      interchangeable, and this could influence their genetic fates. This study
      explores evolution and expression of a simple duplicated complex--a heterodimer
      between RAG1 and RAG2 proteins in clawed frogs (Xenopus). Results demonstrate
      that copies of RAG1 degenerated in different polyploid species in a
      phylogenetically biased fashion, predominately in only one lineage of closely
      related paralogs. Surprisingly, as a result of an early deletion of one RAG2
      paralog, it appears that in many species RAG1/RAG2 heterodimers are composed of
      proteins that were encoded by unlinked paralogs. If the tetraploid ancestor of
      extant species of Xenopus arose through allopolyploidization and if recombination
      between paralogs was rare, then the genes that encode functional RAG1 and RAG2
      proteins in many polyploid species were each ultimately inherited from different
      diploid progenitors. These observations are consistent with the notion that
      ancestry can influence the fate of duplicate genes millions of years after
      duplication, and they uncover a dimension of natural selection in allopolyploid
      genomes that is distinct from other genetic phenomena associated with
      polyploidization or segmental duplication.

PMID- 17435228
TI  - Mitochondrial genome haplotype hypervariation within the isopod parasitic
      nematode Thaumamermis cosgrovei.
AB  - Characterization of mitochondrial genomes from individual Thaumamermis cosgrovei
      nematodes, obligate parasites of the isopod Armadillidium vulgare, revealed that
      numerous mtDNA haplotypes, ranging in size from 19 to 34 kb, are maintained in
      several spatially separated isopod populations. The magnitude and frequency of
      conspecific mtDNA size variation is unprecedented among all studied size
      polymorphic metazoan mitochondrial genomes. To understand the molecular basis of
      this hypervariation, complete nucleotide sequences of two T. cosgrovei mtDNA
      haplotypes were determined. A hypervariable segment, residing between the atp6
      and rrnL genes, contributes exclusively to T. cosgrovei mtDNA size variation.
      Within this region, mtDNA coding genes and putative nonfunctional sequences have
      accumulated substitutions and are duplicated and rearranged to varying extents.
      Hypervariation at this level has enabled a first insight into the life history of
      T. cosgrovei. In five A. vulgare hosts infected with multiple nematodes, four
      carried nematodes with identical mtDNA haplotypes, suggesting that hosts may
      become infected by ingesting a recently hatched egg clutch or become parasitized
      by individuals from the same brood prior to dispersal of siblings within the
      soil.

PMID- 17435229
TI  - A primary assembly of a bovine haplotype block map based on a 15,036-single
      nucleotide polymorphism panel genotyped in holstein-friesian cattle.
AB  - Analysis of data on 1000 Holstein-Friesian bulls genotyped for 15,036 single
      nucleotide polymorphisms (SNPs) has enabled genomewide identification of
      haplotype blocks and tag SNPs. A final subset of 9195 SNPs in Hardy-Weinberg
      equilibrium and mapped on autosomes on the bovine sequence assembly (release Btau
      3.1) was used in this study. The average intermarker spacing was 251.8 kb. The
      average minor allele frequency (MAF) was 0.29 (0.05-0.5). Following recent
      precedents in human HapMap studies, a haplotype block was defined where 95% of
      combinations of SNPs within a region are in very high linkage disequilibrium. A
      total of 727 haplotype blocks consisting of > or =3 SNPs were identified. The
      average block length was 69.7 +/- 7.7 kb, which is approximately 5-10 times
      larger than in humans. These blocks comprised a total of 2964 SNPs and covered
      50,638 kb of the sequence map, which constitutes 2.18% of the length of all
      autosomes. A set of tag SNPs, which will be useful for further fine-mapping
      studies, has been identified. Overall, the results suggest that as many as 75,000
      100,000 tag SNPs would be needed to track all important haplotype blocks in the
      bovine genome. This would require approximately 250,000 SNPs in the discovery
      phase.

PMID- 17435230
TI  - Evidence for de novo evolution of testis-expressed genes in the Drosophila
      yakuba/Drosophila erecta clade.
AB  - The mutational origin and subsequent evolution of de novo genes, which are
      hypothesized to be genes of recent origin that are not obviously related to
      ancestral coding sequence, are poorly understood. However, accumulating evidence
      suggests that such genes may often function in male reproduction. Here we use
      testis-derived expressed sequence tags (ESTs) from Drosophila yakuba to identify
      genes that have likely arisen either in D. yakuba or in the D. yakuba/D. erecta
      ancestor. We found several such genes, which show testis-biased expression and
      are often X-linked. Comparative data indicate that three of these genes have very
      short open reading frames, which suggests the possibility that a significant
      number of testis-biased de novo genes in the D. yakuba/D. erecta clade may be
      noncoding RNA genes. These data, along with previously published data from D.
      melanogaster, support the idea that many de novo Drosophila genes function in
      male reproduction and that a small region of the X chromosome in the melanogaster
      subgroup may be a hotspot for the evolution of novel testis-biased genes.

PMID- 17435231
TI  - Characterization of BEAF mutations isolated by homologous recombination in
      Drosophila.
AB  - The Drosophila BEAF-32A and BEAF-32B proteins bind to the scs' insulator and to
      hundreds of other sites on Drosophila chromosomes. These two proteins are encoded
      by the same gene. We used ends-in homologous recombination to generate the null
      BEAF(AB-KO) allele and also isolated the BEAF(A-KO) allele that eliminates
      production of only the BEAF-32A protein. We find that the BEAF proteins together
      are essential, but BEAF-32B alone is sufficient to obtain viable flies. Our
      results show that BEAF is important for both oogenesis and development. Maternal
      or zygotic BEAF is sufficient to obtain adults, although having only maternal
      BEAF impairs female fertility. In the absence of all BEAF, a few fertile but
      sickly males are obtained. Using both a chromosomal position-effect assay and an
      enhancer-blocking assay, we find that BEAF is necessary for scs' insulator
      function. Lack of BEAF causes a disruption of male X polytene chromosome
      morphology. However, we did not find evidence that dosage compensation was
      affected. Position-effect variegation of the w(m4h) allele and different
      variegating y transgenes was enhanced by the knockout mutation. Combined with the
      effects on male X polytene chromosomes, we conclude that BEAF function affects
      chromatin structure or dynamics.

PMID- 17435232
TI  - Estimating the number of ancestral lineages using a maximum-likelihood method
      based on rejection sampling.
AB  - Estimating the number of ancestral lineages of a sample of DNA sequences at time
      t in the past can be viewed as a variation on the problem of estimating the time
      to the most recent common ancestor. To estimate the number of ancestral lineages,
      we develop a maximum-likelihood approach that takes advantage of a prior model of
      population demography, in addition to the molecular data summarized by the
      pattern of polymorphic sites. The method relies on a rejection sampling algorithm
      that is introduced for simulating conditional coalescent trees given a fixed
      number of ancestral lineages at time t. Computer simulations show that the number
      of ancestral lineages can be estimated accurately, provided that the number of
      mutations that occurred since time t is sufficiently large. The method is applied
      to 986 present-day human sequences located in hypervariable region 1 of the
      mitochondrion to estimate the number of ancestral lineages of modern humans at
      the time of potential admixture with the Neanderthal population. Our estimates
      support a view that the proportion of the modern population consisting of
      Neanderthal contributions must be relatively small, less than approximately 5%,
      if the admixture happened as recently as 30,000 years ago.

PMID- 17435234
TI  - Shortcut predictions for fitness properties at the mutation-selection-drift
      balance and for its buildup after size reduction under different management
      strategies.
AB  - For populations at the mutation-selection-drift (MSD) balance, I develop
      approximate analytical expressions giving expectations for the number of
      deleterious alleles per gamete, the number of loci at which any individual is
      homozygous for deleterious alleles, the inbreeding depression rate, and the
      additive and dominant components of fitness variance. These predictions are
      compared to diffusion ones, showing good agreement under a wide range of
      situations. I also give approximated analytical predictions for the changes in
      mean and additive variance for fitness when a population approaches a new
      equilibrium after its effective size is reduced to a stable value. Results are
      derived for populations maintained with equal family contribution or with no
      management after size reduction, when selection acts through viability or
      fertility differences. Predictions are compared to previously published results
      obtained from transition matrices or stochastic simulations, a good qualitative
      fit being obtained. Predictions are also obtained for populations of various
      sizes under different sets of plausible mutational parameters. They are compared
      to available empirical results for Drosophila, and conservation implications are
      discussed.

PMID- 17435233
TI  - Gametogenesis in the Chlamydomonas reinhardtii minus mating type is controlled by
      two genes, MID and MTD1.
AB  - In the unicellular algae Chlamydomonas reinhardtii, the plus and minus mating
      types are controlled by a complex locus, MT, where the dominant MID gene in the
      MT(-) locus has been shown to be necessary for expression of minus-specific
      gamete-specific genes in response to nitrogen depletion. We report studies on MID
      expression patterns during gametogenesis and on a second gene unique to the MT(-)
      locus, MTD1. Vegetative cells express basal levels of MID. An early activation of
      MID transcription after nitrogen removal, and its sequence similarity to plant
      RWP-RK proteins involved in nitrogen-responsive processes, suggest that Mid
      conformation/activity may be nitrogen sensitive. A second stage of MID
      upregulation correlates with the acquisition of mating ability in minus gametes.
      Knockdown of MTD1 by RNAi in minus strains results in a failure to differentiate
      into gametes of either mating type after nitrogen deprivation. We propose that
      intermediate Mid levels are sufficient to activate MTD1 transcription and to
      repress plus gamete-specific genes and that MTD1 expression in turn allows the
      threshold-level MID expression needed to turn on minus gamete-specific genes. We
      further propose that an MTD1-equivalent system, utilizing at least one gene
      product encoded in the MT(+) locus, is operant during plus gametogenesis.

PMID- 17435236
TI  - Genetic modifiers of the Drosophila blue cheese gene link defects in lysosomal
      transport with decreased life span and altered ubiquitinated-protein profiles.
AB  - Defects in lysosomal trafficking pathways lead to decreased cell viability and
      are associated with progressive disorders in humans. Previously we have found
      that loss-of-function (LOF) mutations in the Drosophila gene blue cheese (bchs)
      lead to reduced adult life span, increased neuronal death, and widespread CNS
      degeneration that is associated with the formation of ubiquitinated-protein
      aggregates. To identify potential genes that participate in the bchs functional
      pathway, we conducted a genetic modifier screen based on alterations of an eye
      phenotype that arises from high-level overexpression of Bchs. We found that
      mutations in select autophagic and endocytic trafficking genes, defects in
      cytoskeletal and motor proteins, as well as mutations in the SUMO and ubiquitin
      signaling pathways behave as modifiers of the Bchs gain-of-function (GOF) eye
      phenotype. Individual mutant alleles that produced viable adults were further
      examined for bchs-like phenotypes. Mutations in several lysosomal trafficking
      genes resulted in significantly decreased adult life spans and several mutants
      showed changes in ubiquitinated protein profiles as young adults. This work
      represents a novel approach to examine the role that lysosomal transport and
      function have on adult viability. The genes characterized in this study have
      direct human homologs, suggesting that similar defects in lysosomal transport may
      play a role in human health and age-related processes.

PMID- 17435235
TI  - Asymmetric postmating isolation: Darwin's corollary to Haldane's rule.
AB  - Asymmetric postmating isolation, where reciprocal interspecific crosses produce
      different levels of fertilization success or hybrid sterility/inviability, is
      very common. Darwin emphasized its pervasiveness in plants, but it occurs in all
      taxa assayed. This asymmetry often results from Dobzhansky-Muller
      incompatibilities (DMIs) involving uniparentally inherited genetic factors (e.g.,
      gametophyte-sporophyte interactions in plants or cytoplasmic-nuclear
      interactions). Typically, unidirectional (U) DMIs act simultaneously with
      bidirectional (B) DMIs between autosomal loci that affect reciprocal crosses
      equally. We model both classes of two-locus DMIs to make quantitative and
      qualitative predictions concerning patterns of isolation asymmetry in parental
      species crosses and in the hybrid F(1) generation. First, we find conditions that
      produce expected differences. Second, we present a stochastic analysis of DMI
      accumulation to predict probable levels of asymmetry as divergence time
      increases. We find that systematic interspecific differences in relative rates of
      evolution for autosomal vs. nonautosomal loci can lead to different expected F(1)
      fitnesses from reciprocal crosses, but asymmetries are more simply explained by
      stochastic differences in the accumulation of U DMIs. The magnitude of asymmetry
      depends primarily on the cumulative effects of U vs. B DMIs (which depend on
      heterozygous effects of DMIs), the average number of DMIs required to produce
      complete reproductive isolation (more asymmetry occurs when fewer DMIs are
      required), and the shape of the function describing how fitness declines as DMIs
      accumulate. Comparing our predictions to data from diverse taxa indicates that
      unidirectional DMIs, specifically involving sex chromosomes, cytoplasmic
      elements, and maternal effects, are likely to play an important role in
      postmating isolation.

PMID- 17435237
TI  - Genetic architecture of conspecific sperm precedence in Allonemobius fasciatus
      and A. socius.
AB  - The evolution of barriers to gene exchange is centrally important to speciation.
      We used the crickets Allonemobius fasciatus and A. socius to investigate the
      genetic architecture of conspecific sperm precedence (CSP), a postinsemination
      prezygotic reproductive barrier. With amplified fragment-length polymorphism
      (AFLP) markers and controlled crosses we constructed linkage maps and estimated
      positions of QTL associated with CSP. The majority of QTL have low to moderate
      effects, although a few QTL exist in A. socius with large effects, and the
      numbers of QTL are comparable to numbers of genes accounting for species
      differences in other studies. The QTL are spread across many unlinked markers,
      yet QTL placed with linked markers are on a small number of linkage groups that
      could reflect the role of the large Allonemobius sex chromosome in prezygotic
      isolation. Although many QTL had positive effects on conspecific sperm
      utilization several QTL also exerted negative effects, which could be explained
      by intraspecific sexual conflict, sperm competition, or epistasis of introgressed
      genes on novel backgrounds. One unexpected outcome was that A. socius CSP alleles
      have a stronger effect than those from A. fasciatus in hybrid females, causing
      hybrids to behave like A. socius with regard to sperm utilization. Implications
      of this asymmetry in the Allonemobius hybrid zone are discussed.

PMID- 17435238
TI  - Associations between sperm competition and natural variation in male reproductive
      genes on the third chromosome of Drosophila melanogaster.
AB  - We applied association analysis to elucidate the genetic basis for variation in
      phenotypes affecting postcopulatory sexual selection in a natural population of
      Drosophila melanogaster. We scored 96 third chromosome substitution lines for
      nine phenotypes affecting sperm competitive ability and genotyped them at 72
      polymorphisms in 13 male reproductive genes. Significant heterogeneity among
      lines (P < 0.01) was detected for all phenotypes except male-induced
      refractoriness (P = 0.053). We identified 24 associations (8 single-marker
      associations, 12 three-marker haplotype associations, and 4 cases of epistasis
      revealed by single-marker interactions). Fewer than 9 of these associations are
      likely to be false positives. Several associations were consistent with previous
      findings [Acp70A with the male's influence on the female's refractoriness to
      remating (refractory), Esterase-6 with a male's remating probability (remating)
      and a measure of female offspring production (fecundity)], but many are novel
      associations with uncharacterized seminal fluid proteins. Four genes showed
      evidence for pleiotropic effects [CG6168 with a measure of sperm competition
      (P2') and refractory, CG14560 with a defensive measure of sperm competition (P1')
      and a measure of female fecundity, Acp62F with P2' and a measure of female
      fecundity, and Esterase-6 with remating and a measure of female fecundity]. Our
      findings provide evidence that pleiotropy and epistasis are important factors in
      the genetic architecture of male reproductive success and show that haplotype
      analyses can identify associations missed in the single-marker approach.

PMID- 17435239
TI  - Bayesian shrinkage analysis of quantitative trait Loci for dynamic traits.
AB  - Many quantitative traits are measured repeatedly during the life of an organism.
      Such traits are called dynamic traits. The pattern of the changes of a dynamic
      trait is called the growth trajectory. Studying the growth trajectory may enhance
      our understanding of the genetic architecture of the growth trajectory. Recently,
      we developed an interval-mapping procedure to map QTL for dynamic traits under
      the maximum-likelihood framework. We fit the growth trajectory by Legendre
      polynomials. The method intended to map one QTL at a time and the entire QTL
      analysis involved scanning the entire genome by fitting multiple single-QTL
      models. In this study, we propose a Bayesian shrinkage analysis for estimating
      and mapping multiple QTL in a single model. The method is a combination between
      the shrinkage mapping for individual quantitative traits and the Legendre
      polynomial analysis for dynamic traits. The multiple-QTL model is implemented in
      two ways: (1) a fixed-interval approach where a QTL is placed in each marker
      interval and (2) a moving-interval approach where the position of a QTL can be
      searched in a range that covers many marker intervals. Simulation study shows
      that the Bayesian shrinkage method generates much better signals for QTL than the
      interval-mapping approach. We propose several alternative methods to present the
      results of the Bayesian shrinkage analysis. In particular, we found that the Wald
      test-statistic profile can serve as a mechanism to test the significance of a
      putative QTL.

PMID- 17435240
TI  - Why are there still over 1000 uncharacterized yeast genes?
AB  - The yeast genetics community has embraced genomic biology, and there is a general
      understanding that obtaining a full encyclopedia of functions of the
      approximately 6000 genes is a worthwhile goal. The yeast literature comprises
      over 40,000 research papers, and the number of yeast researchers exceeds the
      number of genes. There are mutated and tagged alleles for virtually every gene,
      and hundreds of high-throughput data sets and computational analyses have been
      described. Why, then, are there >1000 genes still listed as uncharacterized on
      the Saccharomyces Genome Database, 10 years after sequencing the genome of this
      powerful model organism? Examination of the currently uncharacterized gene set
      suggests that while some are small or newly discovered, the vast majority were
      evident from the initial genome sequence. Most are present in multiple genomics
      data sets, which may provide clues to function. In addition, roughly half contain
      recognizable protein domains, and many of these suggest specific metabolic
      activities. Notably, the uncharacterized gene set is highly enriched for genes
      whose only homologs are in other fungi. Achieving a full catalog of yeast gene
      functions may require a greater focus on the life of yeast outside the
      laboratory.

PMID- 17435241
TI  - Loss-of-function alleles of the JIL-1 histone H3S10 kinase enhance position
      effect variegation at pericentric sites in Drosophila heterochromatin.
AB  - In this study we show that loss-of-function alleles of the JIL-1 histone H3S10
      kinase act as enhancers of position-effect variegation at pericentric sites
      whereas the gain-of-function JIL-1(Su(var)3-1[3]) allele acts as a suppressor
      strongly supporting a functional role for JIL-1 in maintaining euchromatic
      chromatin and counteracting heterochromatic spreading and gene silencing.

PMID- 17435242
TI  - Adaptive walks toward a moving optimum.
AB  - We investigate how the dynamics and outcomes of adaptation by natural selection
      are affected by environmental stability by simulating adaptive walks in response
      to an environmental change of fixed magnitude but variable speed. Here we
      consider monomorphic lineages that adapt by the sequential fixation of beneficial
      mutations. This is modeled by selecting short RNA sequences for folding stability
      and secondary structure conservation at increasing temperatures. Using short RNA
      sequences allows us to describe adaptive outcomes in terms of genotype (sequence)
      and phenotype (secondary structure) and to follow the dynamics of fitness
      increase. We find that slower rates of environmental change affect the dynamics
      of adaptive walks by reducing the fitness effect of fixed beneficial mutations,
      as well as by increasing the range of time in which the substitutions of largest
      effect are likely to occur. In addition, adaptation to slower rates of
      environmental change results in fitter endpoints with fewer possible end
      phenotypes relative to lineages that adapt to a sudden change. This suggests that
      care should be taken when experiments using sudden environmental changes are used
      to make predictions about adaptive responses to gradual change.

PMID- 17435243
TI  - Genetic mapping of developmental instability: design, model and algorithm.
AB  - Developmental instability or noise, defined as the phenotypic imprecision of an
      organism in the face of internal or external stochastic disturbances, has been
      thought to play an important role in shaping evolutionary processes and patterns.
      The genetic studies of developmental instability have been based on fluctuating
      asymmetry (FA) that measures random differences between the left and the right
      sides of bilateral traits. In this article, we frame an experimental design
      characterized by a spatial autocorrelation structure for determining the genetic
      control of developmental instability for those traits that cannot be bilaterally
      measured. This design allows the residual environmental variance of a
      quantitative trait to be dissolved into two components due to permanent and
      random environmental factors. The degree of developmental instability is
      quantified by the relative proportion of the random residual variance to the
      total residual variance. We formulate a mixture model to estimate and test the
      genetic effects of quantitative trait loci (QTL) on the developmental instability
      of the trait. The genetic parameters including the QTL position, the QTL effects,
      and spatial autocorrelations are estimated by implementing the EM algorithm
      within the mixture model framework. Simulation studies were performed to
      investigate the statistical behavior of the model. A live example for poplar
      trees was used to map the QTL that control root length growth and its
      developmental instability from cuttings in water culture.

PMID- 17435245
TI  - Multiple trans-sensing interactions affect meiotically heritable epigenetic
      states at the maize pl1 locus.
AB  - Interactions between specific maize purple plant1 (pl1) alleles result in
      heritable changes of gene regulation that are manifested as differences in
      anthocyanin pigmentation. Transcriptionally repressed states of Pl1-Rhoades
      alleles (termed Pl') are remarkably stable and invariably facilitate heritable
      changes of highly expressed states (termed Pl-Rh) in Pl'/Pl-Rh plants. However,
      Pl' can revert to Pl-Rh when hemizygous, when heterozygous with pl1 alleles other
      than Pl1-Rhoades, or in the absence of trans-acting factors required to maintain
      repressed states. Cis-linked features of Pl1-Rhoades responsible for these trans
      sensing behaviors remain unknown. Here, genetic tests of a pl1 allelic series
      identify two potentially separate cis-linked features: one facilitating
      repression of Pl-Rh and another stabilizing Pl' in trans. Neither function is
      affected in ethyl-methanesulfonate-induced Pl1-Rhoades derivatives that produce
      truncated PL1 peptides, indicating that PL1 is unlikely to mediate trans
      interactions. Both functions, however, are impaired in a spontaneous Pl1-Rhoades
      derivative that fails to produce detectable pl1 RNA. Pl'-like states can also
      repress expression of a pl1-W22 allele, but this repression is not meiotically
      heritable. As the Pl' state is not associated with unique small RNA species
      representing the pl1-coding region, the available data suggest that interactions
      between elements required for transcription underlie Pl1-Rhoades epigenetic
      behaviors.

PMID- 17435244
TI  - Origin and evolution of human microRNAs from transposable elements.
AB  - We sought to evaluate the extent of the contribution of transposable elements
      (TEs) to human microRNA (miRNA) genes along with the evolutionary dynamics of TE
      derived human miRNAs. We found 55 experimentally characterized human miRNA genes
      that are derived from TEs, and these TE-derived miRNAs have the potential to
      regulate thousands of human genes. Sequence comparisons revealed that TE-derived
      human miRNAs are less conserved, on average, than non-TE-derived miRNAs. However,
      there are 18 TE-derived miRNAs that are relatively conserved, and 14 of these are
      related to the ancient L2 and MIR families. Comparison of miRNA vs. mRNA
      expression patterns for TE-derived miRNAs and their putative target genes showed
      numerous cases of anti-correlated expression that are consistent with regulation
      via mRNA degradation. In addition to the known human miRNAs that we show to be
      derived from TE sequences, we predict an additional 85 novel TE-derived miRNA
      genes. TE sequences are typically disregarded in genomic surveys for miRNA genes
      and target sites; this is a mistake. Our results indicate that TEs provide a
      natural mechanism for the origination miRNAs that can contribute to regulatory
      divergence between species as well as a rich source for the discovery of as yet
      unknown miRNA genes.

PMID- 17435246
TI  - A polygenic hypothesis for sex determination in the European sea bass
      Dicentrarchus labrax.
AB  - Polygenic sex determination, although suspected in several species, is thought to
      be evolutionarily unstable and has been proven in very few cases. In the European
      sea bass, temperature is known to influence the sex ratio. We set up a factorial
      mating, producing 5.893 individuals from 253 full-sib families, all reared in a
      single batch to avoid any between-families environmental effects. The proportion
      of females in the offspring was 18.3%, with a large variation between families.
      Interpreting sex as a threshold trait, the heritability estimate was 0.62 +/-
      0.12. The observed distribution of family sex ratios was in accordance with a
      polygenic model or with a four-sex-factors system with environmental variance and
      could not be explained by any genetic model without environmental variance. We
      showed that there was a positive genetic correlation between weight and sex (r(A)
      = 0.50 +/- 0.09), apart from the phenotypic sex dimorphism in favor of females.
      This supports the hypothesis that a minimum size is required for sea bass
      juveniles to differentiate as females. An evolution of sex ratio by frequency
      dependent selection is expected during the domestication process of Dicentrarchus
      labrax populations, raising concern about the release of such fish in the wild.

PMID- 17435247
TI  - Involvement of the mitochondrial protein translocator component tim50 in growth,
      cell proliferation and the modulation of respiration in Drosophila.
AB  - Allelic mutants exhibiting growth defects in Drosophila were isolated. Molecular
      cloning identified the responsible gene as a budding yeast Tim50 ortholog, and
      thus it was named tiny tim 50 (ttm50). The weak allele (ttm50(Gp99)) produced
      small flies due to reduced cell size and number, and growth terminated at the
      larval stage in the strong alleles (ttm50(IE1) and ttm50(IE2)). Twin-spot
      analysis showed fewer cells in ttm50(Gp99) clones, whereas ttm50(IE1) clones did
      not proliferate, suggesting that the gene has an essential cellular function.
      Tim50 is known to maintain mitochondrial membrane potential (MMP) while
      facilitating inner-membrane protein transport. We found that tagged Ttm50 also
      localized to mitochondria and that mitochondrial morphology and MMP were affected
      in mutants, indicating that mitochondrial dysfunction causes the developmental
      phenotype. Conversely, ttm50 overexpression increased MMP and apoptosis. Co
      expression of p35 suppressed this apoptosis, resulting in cell overproliferation.
      Interestingly, ttm50 transcription was tissue specific, corresponding to elevated
      MMP in the larval midgut, which was decreased in the mutant. The correlation of
      ttm50 expression levels with differences in MMP match its proposed role in
      mitochondrial permeability barrier maintenance. Thus a mitochondrial protein
      translocase component can play active roles in regulating metabolic levels,
      possibly for modulation of physiological function or growth in development.

PMID- 17435249
TI  - Fatty acid desaturation and the regulation of adiposity in Caenorhabditis
      elegans.
AB  - Monounsaturated fatty acids are essential components of membrane and storage
      lipids. Their synthesis depends on the conversion of saturated fatty acids to
      unsaturated fatty acids by Delta9 desaturases. Caenorhabditis elegans has three
      Delta9 desaturases encoded by the genes fat-5, fat-6, and fat-7. We generated
      nematodes that display a range of altered fatty acid compositions by constructing
      double-mutant strains that combine mutations in fat-5, fat-6, and fat-7. All
      three double-mutant combinations have reduced survival at low temperatures. The
      fat-5;fat-6 double mutants display relatively subtle fatty acid composition
      alterations under standard conditions, but extreme fatty acid composition changes
      and reduced survival in the absence of food. The strain with the most severe
      defect in the production of unsaturated fatty acids, fat-6;fat-7, exhibits slow
      growth and reduced fertility. Strikingly, the fat-6;fat-7 double-mutant animals
      have decreased fat stores and increased expression of genes involved in fatty
      acid oxidation. We conclude that the Delta9 desaturases, in addition to
      synthesizing unsaturated fatty acids for properly functioning membranes, play key
      roles in lipid partitioning and in the regulation of fat storage.

PMID- 17435250
TI  - A Bayesian multilocus association method: allowing for higher-order interaction
      in association studies.
AB  - For most common diseases with heritable components, not a single or a few single
      nucleotide polymorphisms (SNPs) explain most of the variance for these disorders.
      Instead, much of the variance may be caused by interactions (epistasis) among
      multiple SNPs or interactions with environmental conditions. We present a new
      powerful statistical model for analyzing and interpreting genomic data that
      influence multifactorial phenotypic traits with a complex and likely polygenic
      inheritance. The new method is based on Markov chain Monte Carlo (MCMC) and
      allows for identification of sets of SNPs and environmental factors that when
      combined increase disease risk or change the distribution of a quantitative
      trait. Using simulations, we show that the MCMC method can detect disease
      association when multiple, interacting SNPs are present in the data. When
      applying the method on real large-scale data from a Danish population-based
      cohort, multiple interactions are identified that severely affect serum
      triglyceride levels in the study individuals. The method is designed for
      quantitative traits but can also be applied on qualitative traits. It is
      computationally feasible even for a large number of possible interactions and
      differs fundamentally from most previous approaches by entertaining nonlinear
      interactions and by directly addressing the multiple-testing problem.

PMID- 17435251
TI  - Mutations in cytochrome c oxidase subunit VIa cause neurodegeneration and motor
      dysfunction in Drosophila.
AB  - Mitochondrial dysfunction is involved in many neurodegenerative disorders in
      humans. Here we report mutations in a gene (designated levy) that codes for
      subunit VIa of cytochrome c oxidase (COX). The mutations were identified by the
      phenotype of temperature-induced paralysis and showed the additional phenotypes
      of decreased COX activity, age-dependent bang-induced paralysis, progressive
      neurodegeneration, and reduced life span. Germ-line transformation using the
      levy(+) gene rescued the mutant flies from all phenotypes including
      neurodegeneration. The data from levy mutants reveal a COX-mediated pathway in
      Drosophila, disruption of which leads to mitochondrial encephalomyopathic effects
      including neurodegeneration, motor dysfunction, and premature death. The data
      present the first case of a mutation in a nuclear-encoded structural subunit of
      COX that causes mitochondrial encephalomyopathy rather than lethality, whereas
      several previous attempts to identify such mutations have not been successful.
      The levy mutants provide a genetic model to understand the mechanisms underlying
      COX-mediated mitochondrial encephalomyopathies and to explore possible
      therapeutic interventions.

PMID- 17435252
TI  - Retrotransposons influence the mouse transcriptome: implication for the
      divergence of genetic traits.
AB  - Massive accumulation of retrotransposons, comprising >40% of human and mouse
      genomes, is one of the major events in the evolution of the genome. However, most
      retrotransposons have lost retrotransposition competency, which makes studying
      their role in genome evolution elusive. Intracisternal A-particle (IAP) elements
      are long terminal repeat (LTR)-type mouse retrotransposons consisting of full
      length and internally deleted types. Some are retrotransposition competent and
      their upregulated activity has been reported in mutant mice deficient in genome
      defense systems, suggesting that IAP elements provide a unique platform for
      studying the interaction between retrotransposons and mammalian genomes. Using
      the IAP element as a model case, here we show that mobilization of
      retrotransposons alters the mouse transcriptome. Retrotransposition assay in
      cultured cells demonstrated that a subset of internally deleted IAP elements,
      called IDelta1 type, retrotranspose efficiently when supplied with functional IAP
      proteins. Furthermore, the IDelta1 type IAP element exhibited substantial
      transcription-inducing activity in the flanking region. Genomewide transcript
      analysis of embryonic stem (ES) cells identified IAP-induced transcripts,
      including fusion transcripts between IAP sequence and endogenous genes.
      Unexpectedly, nearly half of these IAP elements obtained from ES cells derived
      from 129 mouse strain were absent in the C57BL/6 genome, suggesting that IAP
      driven transcription contributes to the unique trait of the individual mouse
      strain. On the basis of these data, we propose that retrotransposons are one of
      the drivers that shape the mammalian transcriptome.

PMID- 17435253
TI  - Sex-specific viability, sex linkage and dominance in genomic imprinting.
AB  - Genomic imprinting is a phenomenon by which the expression of an allele at a
      locus depends on the parent of origin. Two different two-locus evolutionary
      models are presented in which a second locus modifies the imprinting status of
      the primary locus, which is under differential selection in males and females. In
      the first model, a modifier allele that imprints the primary locus invades the
      population when the average dominance coefficient among females and males is >12
      and selection is weak. The condition for invasion is always heavily contingent
      upon the extent of dominance. Imprinting is more likely in the sex experiencing
      weaker selection only under some parameter regimes, whereas imprinting by either
      sex is equally likely under other regimes. The second model shows that a modifier
      allele that induces imprinting will increase when imprinting has a direct
      selective advantage. The results are not qualitatively dependent on whether the
      modifier locus is autosomal or X linked.

PMID- 17435254
TI  - Relationship between synovial fluid and plasma manganese, arginase, and nitric
      oxide in patients with rheumatoid arthritis.
AB  - Nitric oxide (NO) participates in the pathogenesis of inflammatory reactions in
      many autoimmune diseases such as rheumatoid arthritis (RA). There is a reciprocal
      pathway between arginase and nitric oxide synthase (NOS) for NO production, and
      Mn is required for arginase activity and stability. To investigate whether NO
      production related with the arginine-nitric oxide pathway in patients with RA, we
      measured synovial fluid and plasma nitrite (NOx) levels, arginase activities, and
      its cofactor manganese (Mn) concentrations in 21 RA patients and 13 healthy
      control subjects. Plasma albumin levels were measured as an index of nutritional
      status. NOx levels were determined after the reduction of nitrates to nitrites
      using the Griess reaction. Whereas, synovial fluid arginase activities and Mn
      levels were found to be significantly lower (p<0.001, p<0.001, respectively),
      plasma arginase activities and Mn levels were similar in patients with RA when
      compared to the control subjects. Plasma and synovial fluid NO levels were
      similar in patients with RA and in healthy subjects (p>0.05, p>0.05,
      respectively). There were significantly positive correlations between synovial
      fluid and plasma arginase activities vs Mn content (r=0.543, p=0.011; r=0.516,
      p=0.017, respectively) and significantly negative correlations between synovial
      fluid and plasma NO levels vs arginase activities (r=-0.497, p=0.022; r=-0.508,
      p=0.019 respectively) in the patients group. Our results indicate that the lower
      concentration of synovial fluid Mn could cause lower arginase activity and this
      could also upregulate NO production by increasing L-arginine content in patients
      with RA.

PMID- 17435248
TI  - The genetic architecture of shoot branching in Arabidopsis thaliana: a
      comparative assessment of candidate gene associations vs. quantitative trait
      locus mapping.
AB  - Association mapping focused on 36 genes involved in branch development was used
      to identify candidate genes for variation in shoot branching in Arabidopsis
      thaliana. The associations between four branching traits and moderate-frequency
      haplogroups at the studied genes were tested in a panel of 96 accessions from a
      restricted geographic range in Central Europe. Using a mixed-model association
      mapping method, we identified three loci--MORE AXILLARY GROWTH 2 (MAX2), MORE
      AXILLARY GROWTH 3 (MAX3), and SUPERSHOOT 1 (SPS1)--that were significantly
      associated with branching variation. On the basis of a more extensive examination
      of the MAX2 and MAX3 genomic regions, we find that linkage disequilibrium in
      these regions decays within approximately 10 kb and trait associations localize
      to the candidate genes in these regions. When the significant associations are
      compared to relevant quantitative trait loci (QTL) from previous Ler x Col and
      Cvi x Ler recombinant inbred line (RIL) mapping studies, no additive QTL
      overlapping these candidate genes are observed, although epistatic QTL for
      branching, including one that spans the SPS1, are found. These results suggest
      that epistasis is prevalent in determining branching variation in A. thaliana and
      may need to be considered in linkage disequilibrium mapping studies of
      genetically diverse accessions.

PMID- 17435255
TI  - Relation of dental wear to the concentrations of essential minerals in teeth of
      the California sea lion Zalophus californianus californianus.
AB  - Tooth wear in marine mammals has been attributed to age, feeding habits,
      behavior, and contaminants. Advanced tooth wear in some California sea lions,
      including some of very young age (<5 yr), in the Gulf of California, suggests
      that there are variations in chemical composition of tooth parts, wherein the
      concentrations of certain trace minerals might be anomalous, making them more
      susceptible to erosion. The concentrations of the essential minerals Ca, P, K,
      Na, Fe, Mg, and Zn in the dentition of Zalophus c. californianus are documented
      for the first time and are compared for sea lion teeth with different degrees of
      wear. Canine teeth and molars from 45 skulls collected at 15 localities since
      1978 were digested in perchloric acid and analyzed using atomic adsorption
      spectrometry, the results being expressed in milligrams per 100 g. An index of
      tooth wear (Id) was established, involving the average wear on the teeth and the
      age of the organism. No significant difference was detected in the variables, but
      there was one between ages (p = 0.02). A higher degree of wear was observed up to
      7 yr of age than from this age onward. Mineral concentrations did not explain the
      excessive wear observed (correlation, p > 0.09; ANOVA, p > 0.15); however, the Ca
      concentration of the teeth was inversely proportional to the age of the animal
      (sexes combined, p = 0.026) and particularly significant for the females (r2 =
      0.112, r = -0.335, p = 0.039). Females could be more prone to decalcification
      because of their annual bone investment in their offspring. Animals of both sexes
      were susceptible to tooth wear as their age increased, but the higher frequency
      of animals between 4 and 7 yr suggests an impact on survival at early stages
      probably linked to deficient feeding and chronic malnutrition.

PMID- 17435256
TI  - Transmission electron microscopy study of the effects of cadmium and copper on
      fetal rat liver tissue.
AB  - During the entire period of their pregnancies, three groups of adult pregnant
      Wistar albino rats were provided with tap water (control; group I) or with tap
      water containing 10 mg/kg CdCl2 (group II) or 10 mg/kg CdCl2 plus 10 mg/kg CuSO4
      (group III). At term, the animals were sacrificed and the fetal livers were
      removed and examined under electron microscopy. The liver tissue of the fetuses
      in maternal groups II and III showed degenerative changes to their hepatocytes.
      In group II, the smooth endoplasmic reticulum tubules showed dilatation, and the
      mitochondria showed a dense matrix. In group III, some mitochondrial degeneration
      was also seen, with a diluted matrix and mitochondrial dilatation. There were
      also more heterochromatic nuclei and an increased number of ribosomes. None of
      these histopathological changes were present in the fetal liver samples from the
      maternal group I control animals.

PMID- 17435257
TI  - Dietary carbohydrate content influences boron's effect on lipid and protein
      indices in rats.
AB  - The aim of the study was to establish whether an excess or deficiency of dietary
      carbohydrates would influence the effect of boron (B) on lipid, protein, and
      glucose metabolism in laboratory rats. Sixty male Buffalo rats were used in the
      study, divided into six groups fed a control diet or a lower high-carbohydrate
      diet with or without a B supplement (3 mg B/kg fodder). The hemoglobin
      concentration and hematocrit were assessed in whole-blood samples, and the total
      protein, albumin, creatine, glucose, total lipid, and high-density lipoprotein
      (HDL) cholesterol contents in the serum were established. The total cholesterol
      and triacylglycerol contents in liver lipid extracts were also measured. A low
      carbohydrate content in a B-supplemented diet led to an increase in the total
      protein and albumin contents in the serum of the rats compared to the levels for
      the rats on the control and high-carbohydrate B supplemented diets. Under
      conditions of an excess or deficiency of carbohydrates in the diet, B did not
      significantly influence the cholesterol and total lipid contents in the serum.
      Boron's influence on the other metabolic indexes (glucose, HDL cholesterol, and
      triacylglycerol contents in the serum; cholesterol and triacylglycerol contents
      in the liver) was unaffected by the carbohydrate content in the diet.

PMID- 17435258
TI  - Different patterns in the induction of metallothionein mRNA synthesis among
      isoforms after acute ethanol administration.
AB  - The induction of metallothionein (MT) isoform synthesis was investigated in mouse
      cerebral cortex 18 h after oral ethanol administration. The expression of MT-I
      isoform mRNA increased in a dose-dependent manner after ethanol loading at doses
      between 2 g/kg (ethanol/body weight) and 8 g/kg. Lipid peroxide formation,
      measured as the amount of malondialdehyde- reactive substances, remained at the
      control level after all of the administered ethanol doses. The expression of MT
      III isoform mRNA remained at the control level up until an ethanol loading dose
      of 4 g/kg and then finally increased to a significant level at a dose of 8 g/kg,
      which is almost the LD50 for oral ethanol in mice. The different patterns of MT
      synthesis induction among MT isoforms suggests that the MT-I isoform, which is
      ubiquitous in mammalian tissues, plays a significant role as an antioxidant. On
      the other hand, the MT-III isoform, which has a limited tissue distribution,
      especially in the central nervous system, seems to be implicated in tissue repair
      and/or protection against critical tissue injury.

PMID- 17435259
TI  - Analysis of cadmium and lead in mice organs: effect of Nigella sativa L. (Black
      Cumin) on the distribution and immunosuppressive effect of cadmium-lead mixture
      in mice.
AB  - Analysis and distribution of Pb and Cd in different mice organs, including the
      liver, kidney, spleen, heart, and blood, were evaluated before and after
      treatment with different aqueous concentrations of Nigella sativa (1.25-10.0
      mg/L). Atomic absorption spectrometry was used for analysis of Pb and Cd in these
      organs. Results indicated that the Pb in the unexposed group of mice without
      treatment with N. sativa (black cumin) was in the following order: liver > heart
      > spleen > kidney, and the distribution of Pb in various organs of the unexposed
      group was not affected significantly by N. sativa. Moreover, results of mice
      exposed for Pb show that the Pb concentrations in different organs were reduced
      significantly (p < 0.05) by 72.9%, 63.4%, 72.3%, 66.7%, and 39.5% at a dose of 10
      mg/L of N. sativa for the liver, kidney, heart, spleen, and blood, respectively.
      Furthermore, the distribution of Cd in the unexposed Cd group of mice without
      treatment with N. sativa was in the following order: kidney > heart > spleen >
      liver. Nigella sativa at 10 mg/L reduced Cd levels in mice exposed to Cd by
      75.5%, 83.3%, 47.0%, 95.3%, and 100% in the liver, kidney, heart, spleen, and
      blood, respectively, whereas blood Cd concentrations were lowered to below the
      detection limit of 0.05 mug/L. A 28-d exposure of mice to a Cd-Pb mixture at a
      concentration of 1 ppm in drinking water induced a highly significant inhibition
      (p < 0.0001) of antibody response to human serum (80.5%). The suppressed immune
      responses in mice pretreated with the Cd-Pb mixture were reversed by 43.1% and
      38.9% in the presence of 1.25 and 2.5 mg/mL of N. sativa, respectively, whereas
      higher concentrations (5-10 mg/mL) of N. sativa increased the immunosuppression
      significantly. Nigella sativa at 1.25-10 mg/mL did not induce any significant
      modulation of the antibody response in unexposed mice.

PMID- 17435260
TI  - Gene expression profiles analysis of the growing rat liver in response to
      different zinc status by cDNA microarray analysis.
AB  - The effects of zinc on growing rats were characterized using the dietary zinc
      deficient (ZD) and Zinc-overdose (ZO) models. Zinc deficiency had negative
      effects on the host final body weight and liver zinc content, whereas zinc
      overdose had positive effects. In order to identify the molecular changes in the
      liver responding to dietary zinc status, cDNA microarrays were used to analyze
      the expression pattern of 9753 genes in the livers of rats fed ZD and ZO diet for
      6 wk, compared with zinc-adequate ZA. The mRNA levels for 62 genes were affected
      significantly by the ZD diet, whereas 66 gene transcriptions were markedly
      changed in the ZO diet. Those predominant gene products involved in nitrogen
      metabolism (glutaminase), carbohydrate metabolism (aldolase), lipid metabolism
      (stearoyl-CoA desaturase), growth (insulin-like growth factor-binding protein),
      transcription and translation (zinc-finger protein), immune (natural-killer
      cell), signal transduction (mitogen- activated protein kinase), and ion
      transportation (ATPase Na+/K+ transporting peptide) were clustered. In
      conclusion, a number of mammalian genes related to zinc in the liver were
      identified. The characterization of the genes and their products will allow a
      more comprehensive analysis of the role of zinc in metabolism. Furthermore, the
      mRNA identified could be useful in establishing the mechanisms of zinc in the
      pleiotropic metabolisms in vivo.

PMID- 17435261
TI  - Insights on zinc regulation of food intake and macronutrient selection.
AB  - Zinc (Zn) is an essential trace element required for human beings and animals.
      This divalent cation is involved in many physiological functions, including
      immune and antioxidant function, growth, and reproduction. Deficiency of Zn
      produces several pathological disorders and abnormalities in its metabolism, such
      as anorexia, weight loss, poor efficiency, and growth retardation. Although it
      has been known for more than 50 yr that Zn deficiency regularly and consistently
      causes anorexia in many animal species, the mechanism that causes this phenomenon
      still remains an enigma. The present review describes recent research
      investigating the relationship between Zn deficiency and the regulation of food
      intake, as well as macronutrient selection.

PMID- 17435262
TI  - Study on the toxic effect of lead(II) ion on Escherichia coli.
AB  - The toxic effects of lead(II) have been studied in Escherichia coli cells. Using
      microcalorimetric analysis, it was shown that E. coli growth was inhibited in the
      presence of Pb2+ resulting from damage to the cell membrane and that Pb2+ takes
      part in the metabolism of cells. Treatment with lysozyme confirms damage to the
      cell's outer membrane. Similarities between the ionic radii and charge/radius
      ratio cause Pb(II) to replace Ca(II) at the binding sites of lipopolysacharides,
      leading to rupture of protecting areas on the cell's surface. Consequently, the
      protection and functionality of outer membrane is lost, thus becoming the basis
      for the biological effect of Pb2+ on E. coli.

PMID- 17435264
TI  - Electronic medical records: why today?

PMID- 17435265
TI  - Unstable angina treatment: 2006 update.
AB  - Properly treated, unstable angina and non-Q wave myocardial infarction have low
      hospital mortality, but if untreated, mortality is high. Symptoms and labs
      usually suffice for diagnosis. Abnormal physical findings are rarely helpful and
      often absent. Careful surveillance and management, including invasive management
      in selected cases, substantially reduce long-term risks.

PMID- 17435266
TI  - Childhood obesity: normal variant or serious illness?
AB  - Obesity is a serious medical issue. Problems that develop in children with a high
      body mass index include high blood pressure, asthma, and cardiovascular disease
      at a young age. Obese children also have less upper body strength and decreased
      endurance. Early weight gain in the first week of life predicts later obesity.
      More televisions in the house and greater television watching also correlate with
      more obesity. Although male and female children rarely meet the minimum suggested
      amounts of nutrients, they exceed the suggested number of calories. Managing
      obesity should start before the teenage years. Food education has been shown to
      be an effective method of weight control.

PMID- 17435267
TI  - New mechanism for an old drug: aspirin triggers anti-inflammatory lipid mediators
      with gender implications.
AB  - Aspirin increases anti-inflammatory aspirin-triggered lipoxin A4 levels in
      healthy subjects in a gender-specific manner in a randomized clinical study.
      Thus, formation of aspirin-triggered lipoxin A4 may provide a novel mechanism
      underlying aspirin's clinical benefits, and shed light on gender-dependent
      therapeutics of aspirin.

PMID- 17435268
TI  - Systemic lupus erythematosus: current state of diagnosis and treatment.
AB  - Systemic lupus erythematosus is a chronic autoimmune condition with a wide
      spectrum of clinical manifestations, characterized by the production of auto
      antibodies to components of the cell nucleus. Treatments include various
      immunosuppressive regimens, and newer biological therapies show promising
      results.

PMID- 17435269
TI  - Porphyria syndrome associated with diabetic nephrosclerosis and erythropoietin.
AB  - The porphyrias are inherited or acquired metabolic disorders caused by a partial
      deficiency in one of the enzymes of the heme biosynthetic pathway. Eight enzymes
      are utilized in the synthesis of heme. An enzyme defect in one of the last seven
      enzymes will result in one of the seven different forms of porphyria, some of
      which have similar signs and symptoms. This article describes six diabetic,
      azotemic patients with no prior history of porphyria, who developed a syndrome
      similar to acute intermittent porphyria after initiation of treatment with
      erythropoietin. One of the patients developed the syndrome predialysis, whereas
      the remaining patients were on maintenance hemodialysis. The symptoms varied but
      all resolved when erythropoietin was discontinued and reappeared in four cases
      when erythropoietin was restarted. In all of the patients, the enzyme
      aminolevulinic acid-dehydratase (ALA-D) was low and the uroporphyrinogen synthase
      was normal. This enzyme abnormality suggests an acquired form of delta
      aminolevulinic acid dehydratase porphyria (ADP). Lead toxicity, succinylacetone,
      and zinc deficiency are known to depress ALA-D, but these conditions were not
      present. The development of the acute porphyria syndrome while the patients were
      receiving pharmacological doses of erythropoietin, which resolved when the drug
      was stopped, suggests that by stimulating heme synthesis, erythropoietin may
      unmask an enzyme deficiency resulting in the clinical expression of ADP. The
      patients responded favorably to a regimen that included discontinuation of
      erythropoietin, tight blood sugar control, maintaining the hematocrit above 30%,
      and a KT/V, a measure of dialysis adequacy, of 1.5 in the hemodialysis group.
      Plasmapheresis accelerated the recovery when used in two patients.

PMID- 17435270
TI  - The administration of polymerized human hemoglobin (Pyridoxylated) to a Jehovah's
      Witness after submyeloablative stem cell transplantation complicated by delayed
      graft failure.
AB  - A 55-yr-old woman with a history of B-cell lymphoma of the nasopharynx diagnosed
      in March 1999 eventually underwent submyeloablative allogeneic stem cell
      transplantation from a sibling donor in December 2002 after conventional
      treatment options were exhausted. The treatment approach was somewhat altered by
      the fact that the patient was a practicing Jehovah's Witness and refused blood
      blood product transfusion. The course of her treatment was unremarkable until
      around day 100 posttransplant when she developed graft failure, leading to severe
      anemia. Blood transfusions were refused. Donor cells were re-infused. During this
      treatment period, the patient's hemoglobin dropped to a low of 2.7 g/dL, with the
      patient experiencing severe fatigue, dyspnea on exertion, headaches, and blurred
      vision. Polymerized human hemoglobin (pyridoxylated) (Poly- Heme, Northfield
      Laboratories Inc., Evanston, IL) was given under an emergency, compassionate use
      protocol and successfully bridged the patient's hemoglobin and relieved symptoms
      during her marrow recovery period.

PMID- 17435271
TI  - As if the cancer wasn't enough! Understanding and treating the pain that comes
      with cancer.
AB  - In people with cancer, pain often occurs from the malignancy, from procedures
      done to diagnose, stage, and treat the malignancy, and from the toxicities of
      therapy used in treating the cancer. Of people with cancer, 75% complain of some
      sort of pain. Determining whether the pain is from tissue damage or nerve
      structures will guide therapy. Assessment of the severity of the pain by
      location, oncological type, as well as psychosocial and environmental factors are
      necessary to understand and treat the pain that accompanies cancer. Medical
      interventions include non-opioid analgesics, opioids, and multiple different
      combinations of medications. Adjuvant medication like anticonvulsants and
      steroids are being used frequently to help people feel more comfortable.

PMID- 17435272
TI  - Use of antiplatelet drugs in secondary prevention in patients with
      atherothrombotic disease.
AB  - Unless there are contraindications to the use of aspirin, aspirin should be used
      to treat patients with acute myocardial infarction (MI) and continued
      indefinitely to decrease vascular death, nonfatal MI, and nonfatal stroke.
      Clopidogrel added to aspirin is beneficial in the treatment of patients with
      acute ST-elevation MI. Patients with unstable angina pectoris or non-ST-elevation
      MI should be treated with aspirin plus clopidogrel for at least 9 mo to decrease
      vascular death, nonfatal MI, and nonfatal stroke. Patients with prior MI should
      be treated indefinitely with aspirin and with clopidogrel if aspirin is
      contraindicated. Patients with ischemic stroke should be treated with either
      aspirin or clopidogrel indefinitely. Clopidogrel is significantly more effective
      than aspirin in reducing vascular death, nonfatal MI, and nonfatal stroke in
      patients with peripheral arterial disease.

PMID- 17435273
TI  - Superior vena cava obstruction presenting as a complication of repeated central
      venous cannulations.
AB  - Frequent use of central venous cannulations and dialysis catheters has led to
      increased complications like venous thrombosis and catheter-related sepsis.
      Superior vena cava subclavian obstruction secondary to extensive thrombosis of
      the central veins and internal jugular veins is presented. The risk factors,
      diagnostic modalities, and treatment options are discussed.

PMID- 17435274
TI  - Shin splints: painful to have and to treat.
AB  - When people overuse their legs they develop an uncomfortable awareness of these
      limbs manifested as a dull burning or aching. The cause is often clear to the
      person with the problem as a result of the often obvious relationship to
      overdoing an exercise or activity and the pain. "Shin splints" is the lay term;
      physicians use the term medial tibial stress syndrome. The pathophysiology that
      leads to this pain is unclear, although there are a number of competing theories.
      Differential diagnosis includes stress fractures and compartment syndromes. Bone
      tumors or lipomas can also cause similar pain to shin splints. Diagnosis can be
      made by history alone in a majority of cases, but if the diagnosis is unclear, an
      X-ray and magnetic resonance imaging should be considered. Treatment is still
      mostly supportive and symptom related. Rest is the most important aspect of
      treatment. Locally applied cold and anti-inflammatory medication have also been
      felt to be beneficial.

PMID- 17435275
TI  - Display of adenoregulin with a novel Pichia pastoris cell surface display system.
AB  - Two Pichia pastoris cell surface display vectors were constructed. The vectors
      consisted of the flocculation functional domain of Flo1p with its own secretion
      signal sequence or the alpha-factor secretion signal sequence, a polyhistidine
      (6xHis) tag for detection, an enterokinase recognition site, and the insertion
      sites for target proteins. Adenoregulin (ADR) is a 33-amino-acid antimicrobial
      peptide isolated from Phyllomedusa bicolor skin. The ADR was expressed and
      displayed on the Pichia pastoris KM71 cell surface with the system reported. The
      displayed recombinant ADR fusion protein was detected by fluorescence microscopy
      and confocal laser scanning microscopy (CLSM). The antimicrobial activity of the
      recombinant adenoregulin was detected after proteolytic cleavage of the fusion
      protein on cell surface. The validity of the Pichia pastoris cell surface display
      vectors was proved by the displayed ADR.

PMID- 17435276
TI  - Molecular cloning and characterization of a novel splice variant of the LIM
      domain family gene, PINCH 2, in human testis.
AB  - By hybridizing human adult testis cDNA microarrays with human adult and embryo
      testis cDNA probes, we identified a novel human testis gene, PINCH 2. PINCH 2
      expression was 3.4-fold higher in adult than in fetal testis. The full length of
      its cDNA was 963 bp, with a 354-bp open reading frame (ORF), encoding a 117-amino
      acid protein. PINCH 2 was a splicing isoform of PINCH. It shared one exon, which
      encoded the LIM domain, with PINCH gene in human genome. Multitissue reverse
      transcriptase-polymerase chain reaction (RTPCR) analysis revealed that this gene
      was expressed variably in a wide range of tissues, with high expression levels in
      human adult testis. These results suggest that PINCH 2, a novel LIM domain
      containing gene, may play an important role in testicular
      development/spermatogenesis.

PMID- 17435277
TI  - Detection of Xanthomonas oryzae pv. oryzae in seeds using a specific TaqMan
      probe.
AB  - Xanthomonas oryzae pv. oryzae is the pathogen that causes bacterial leaf blight
      in rice. Bacterial leaf blight is the main cause for severe rice underproduction
      in many countries. However, with conventional methods it is difficult to quickly
      and reliably distinguish this pathogen from other closely related pathogenic
      bacteria, especially X. oryzae pv. oryzicola, the causal organism of bacterial
      leaf streak in rice. We have developed a novel and highly sensitive real-time
      method for the identification of this specific bacteria based on a TaqMan probe.
      This probe is designed to recognize the sequence of a putative siderophore
      receptor gene cds specific to X. oryzae pv. oryzae, and can be identified from
      either a bacterial culture or naturally infected rice seeds and leaves in only 2
      h. The sensitivity of the method is 100 times higher than that of the current
      polymerase chain reaction (PCR) gel electrophoresis method for diagnosis.

PMID- 17435278
TI  - Effects of additives on efficiency and specificity of ligase detection reaction.
AB  - Ligase detection reaction (LDR) is adaptable to a wide variety of applications
      ranging from scientific research to clinical diagnosis, especially in the field
      of nucleotide polymorphism discrimination and analysis. Efficiency and
      specificity of LDR are the most two important characteristics that influence its
      application. To improve the specificity or efficiency of ligase, optimization of
      the design of LDR probes and the reaction of LDR were investigated previously by
      most researchers. But the effects of additives on LDR have not been reported. In
      this study, the effects of additives (DMSO, Tween-20, glycerol, formamide, and
      PEG- 6000) on LDR efficiency and specificity were investigated. The results
      showed that all of these compounds, except for Tween-20, could improve the
      specificity of LDR. PEG-6000 was proved to be the best additive among the five
      tested with an optimal concentration of 5% at which the highest yield was
      obtained with a relatively improved specificity.

PMID- 17435279
TI  - Simultaneous MLPA-based multiplex point mutation and deletion analysis of the
      dystrophin gene.
AB  - The Multiplex Ligation-dependent Probe Amplification assay (MLPA) is the method
      of choice for the initial mutation screen in the analysis of a large number of
      genes where partial or total gene deletion is part of the mutation spectrum.
      Although MLPA dosage probes are usually designed to bind to normal DNA sequence
      to identify dosage imbalance, point mutation-specific MLPA probes can also be
      made. Using the dystrophin gene as a model, we have designed two MLPA probe
      multiplexes that are specific to a number of commonly listed point mutations in
      the Leiden dystrophin point mutation database (http://www.dmd.nl). The point
      mutation probes are designed to work simultaneously with two widely used
      dystrophin MLPA multiplexes, allowing both full dosage analysis and partial point
      mutation analysis in a single test. This approach may be adapted for other
      syndromes with well defined common point mutations or polymorphisms.

PMID- 17435280
TI  - Proteolysis, histopathological effects, and immunohistopathological localization
      of delta-endotoxins of Bacillus thuringiensis subsp. kurstaki in the midgut of
      lepidopteran olive tree pathogenic insect Prays oleae.
AB  - Considering the fact that Prays oleae is one of the most pathogenic insects to
      the olive tree in the Mediterranean basin, particularly in Tunisia, the mode of
      action of Cry insecticidal toxins of Bacillus thuringiensis kurstaki in Prays
      oleae midgut was investigated. The proteolysis of Bacillus thuringiensis delta
      endotoxins in the midgut was a key step in determining their potency against
      Prays oleae. The latter's proteases activated the delta-endotoxins early,
      yielding stable toxins. The in vitro and in vivo binding of these toxins to Prays
      oleae larvae midgut was studied immunohistochemically, evidencing a midgut
      columnar cell vacuolization, microvilli damage, and then a pass of epithelium
      cell content into the larvae midgut. Moreover, Bacillus thuringiensis toxins were
      shown to bind to the apical microvilli of the midgut epithelial cells. The in
      vitro study of the interaction of Prays oleae midgut proteins with biotinylated
      Bacillus thuringiensis toxins allowed the prediction of four suitable receptor
      proteins in Prays oleae.

PMID- 17435281
TI  - Characterization of oligosaccharides from industrial fermentation residues by
      matrix-assisted laser desorption/ionization, electrospray mass spectrometry, and
      gas chromatography mass spectrometry.
AB  - We report here the preliminary characterization of oligosaccharides present in an
      enzyme-treated industrial fermentation residue using matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS),
      electrospray ion trap mass spectrometry (ESI-ITMS), and gas chromatography mass
      spectrometry (GC-MS). After sample cleaning with carbon graphite columns,
      analysis of oligosaccharides present in the sample using MALDI-TOF-MS resulted in
      identification of molecular ions representing sodiated hexose and pentose
      oligo/polysaccharides. The GC-MS analyses revealed that the signals observed in
      the mass spectrum for hexose oligomers represent linear structures, whereas the
      pentose oligomers were identified as arabinoxylans with a (1-->4) linked Xylp
      backbone where the Xylp residues were either not substituted or singly
      substituted with Araf branching residues at positions C-2 or C-3 of the Xylp
      ring. Analyses by ESI-ITMS of the signals corresponding to arabinoxylan
      oligosaccharides with four and five monosaccharide residues showed the presence
      of isomeric structures differing in degree of branching and localization of the
      branched residue along the Xylp backbone.

PMID- 17435282
TI  - Use of thermolysin in the diagnosis of prion diseases.
AB  - The molecular diagnosis of prion diseases almost always involves the use of a
      protease to distinguish PrPC from PrPSc and invariably the protease of choice is
      proteinase K. Here, we have applied the protease thermolysin to the diagnosis of
      animal prion diseases. This thermostable protease cleaves at the hydrophobic
      residues Leu, Ile, Phe, Val, Ala, and Met, residues that are absent from the
      protease accessible aminoterminal region of PrPSc. Therefore, although
      thermolysin readily digests PrPC into small protein fragments, full-length PrPSc
      is resistant to such proteolysis. This contrasts with proteinase K digestion
      where an aminoterminally truncated PrPSc species is produced, PrP27-30.
      Thermolysin was used in the diagnosis of ovine scrapie and bovine spongiform
      encephalopathy and produced comparable assay sensitivity to assays using
      proteinase K digestion. Furthermore, we demonstrated the concentration of
      thermolysin-resistant PrPSc using immobilized metal-affinity chromatography. The
      use of thermolysin to reveal a full-length PrPSc has application for the
      development of novel immunodiagnostics by exploiting the wide range of
      commercially available immunoreagents and metal affinity matrices that bind the
      amino-terminal region of PrP. In addition, thermolysin provides a complementary
      tool to proteinase K to allow the study of the contribution of the amino-terminal
      domain of PrPSc to disease pathogenesis.

PMID- 17435283
TI  - Differentiation between Bacillus thuringiensis strains by gyrB PCR-Sau3AI
      fingerprinting.
AB  - gyrB DNA fragments of seven Bacillus thuringiensis local collection family
      representatives were amplified by PCR and sequenced. Several differences in their
      corresponding sequences were evidenced. Both in silico and in vitro restriction
      maps of gyrB sequences and fragments respectively confirmed that EcoRI and Sau3AI
      could be used to differentiate between B. thuringiensis strains. However, the
      phylogeny analysis showed that only the gyrB PCR-Sau3AI allows a strains
      classification that correlates very well with that obtained on the basis of the
      sequences analysis. Thus, these finds show that gyrB PCR- Sau3AI digestion could
      be considered as an efficient, rapid, and easy method to make a distinction, not
      only between strains belonging to the Bacillus cereus group, but also between
      those belonging to B. thuringiensis.

PMID- 17435284
TI  - Oral administration activity determination of recombinant osteoprotegerin from
      silkworm larvae.
AB  - Osteoprotegerin (OPG) regulates the formation of osteoclasts and is involved in
      the regulation of bone resorption and remodeling. To investigate the feasibility
      of using silkworm (Bombyx mori) larvae to produce recombinant osteoprotegerin as
      a oral administration drug, the rh-OPG was expressed in the larvae of silkworm
      through the silkworm baculovirus expression system, and was orally administered
      to mice. Compared with the control, oral administration of rh-OPG was effective
      to decrease serum calcium concentration in normal mice, and block the bone loss
      induced by the loss of estrogen in ovariectomized mice. These results indicated
      that oral administration of rh-OPG expressed in silkworm larvae had the proper
      bioactivity.

PMID- 17435286
TI  - Characterization of pyramidal inversion boundaries in Sb2O3-doped ZnO by using
      electron back-scattered diffraction (EBSD).
AB  - The composition planes of the inversion boundary induced by the addition of Sb2O3
      to ZnO ceramics were analyzed crystallographically by the application of electron
      back-scattered diffraction (EBSD) analysis and stereographic projection
      techniques. The inversion boundary was determined to consist of three discrete
      composition planes, {0001}, {1011}, {1010}.

PMID- 17435287
TI  - Determination of a one-electron reduced density matrix using a coupled pseudo
      atom model and a set of complementary scattering data.
AB  - A possible model of one-electron reduced density matrices is presented, adapted
      from the Hansen-Coppens pseudo-atomic description of electron density [Hansen &
      Coppens (1978). Acta Cryst. A34, 909-913]. Potential benefits from a joint
      refinement of the model from X-ray diffraction and deep inelastic scattering data
      are illustrated.

PMID- 17435288
TI  - Phase and amplitude recovery and diffraction image generation method: structure
      of Sb/Au(110)-radical3xradical3R54.7 degrees from surface X-ray diffraction.
AB  - The discovery that the phase problem of diffraction from non-periodic objects may
      be solved by oversampling the diffraction intensities in reciprocal space with
      respect to a Nyquist criterion has opened up new vistas for structure
      determination by diffraction methods. A similar principle may be applied to the
      problem of surface X-ray diffraction (SXRD), where, owing to the breaking of a
      crystal periodicity normal to its surface, diffraction data consist of a set of
      superstructure rods (SRs) due to scattering from the parts of the surface whose
      structure is different from that of the truncated bulk and of crystal truncation
      rods (CTRs), formed by interfering contributions from the surface and the bulk. A
      phase and amplitude recovery and diffraction image generation method (PARADIGM)
      is described that provides a prescription for finding the unmeasured amplitudes
      and phases of the surface contributions to the CTRs in addition to the phases of
      the SRs, directly from the diffraction data. The resulting ;diffraction image' is
      the basis of a determination of the previously unknown multidomain structure of
      Sb/Au(110)-radical3xradical3R54.7 degrees.

PMID- 17435289
TI  - Kinematical multiple diffraction: the width of psi-scan intensity profiles.
AB  - It was shown in Rossmanith [Acta Cryst. (1992), A48, 596-610] that the peak width
      of intensity profiles of multiple diffraction events can be calculated in a
      simple manner from the divergence delta and the wavelength spread
      Deltalambda/lambda of the incident beam and from the mosaic spread eta and the
      magnitude r of the ideally perfect crystallites in the sample. In the present
      paper, an improvement of the concept is given.

PMID- 17435285
TI  - Methods and goals for the use of in vitro and in vivo chemosensitivity testing.
AB  - Sensitive, specific, and accurate methods to assay chemosensitivity are needed to
      (1) screen new therapeutic agents, (2) identify patterns of chemosensitivity for
      different tumor types, (3) establish patterns of cross-resistance and sensitivity
      in treatment of naive and relapsing tumors, (4) identify genomic and proteomic
      profiles associated with sensitivity, (5) correlate in vitro response with
      preclinical in vivo effects and clinical outcomes for a particular therapeutic
      agent, and (6) tailor chemotherapy regimens to individual patients. Various
      methods are available to achieve these end points, including several in vitro
      clonogenic and proliferation assays, cell metabolic activity assays, molecular
      assays to monitor expression of markers for responsiveness, drug resistance, and
      for induction of apoptosis, in vivo tumor growth and survival assays in
      metastatic and orthotopic models, and in vivo imaging assays. The advantages and
      disadvantages of the specific assays are discussed. A summary of research
      questions related to chemosensitivity testing is also included.

PMID- 17435290
TI  - The mean-square Friedel intensity difference in P1 with a centrosymmetric
      substructure.
AB  - For non-centrosymmetric structures in space group P1 containing a centrosymmetric
      substructure, analytical expressions have been obtained for various functions of
      the diffraction intensity of Friedel opposites. These functions are the average
      intensity of Friedel opposites, the mean difference in intensity of Friedel
      opposites and the mean-square difference in intensity of Friedel opposites. A
      Bijvoet intensity ratio is defined for the evaluation of resonant-scattering
      effects in non-centrosymmetric and pseudo-centrosymmetric structures. Analysis of
      these expressions confirms that both resonant and non-resonant atoms are
      necessary to produce differences in intensity between Friedel opposites and also
      shows that in some circumstances atoms may lie on a centrosymmetric substructure
      without diminishing the Bijvoet intensity ratio. The effects of the real
      component of resonant scattering, of the variation of the scattering factors with
      sin theta/lambda, of isotropic atomic displacement parameters, of a crystal
      twinned by inversion, of atoms in special positions and of weak reflections are
      considered. Software is available for the evaluation of the Bijvoet intensity
      ratio.

PMID- 17435291
TI  - A simple method of determining the form of the phonon part of tensors describing
      quasicrystal properties.
AB  - It is shown that the restrictions on the form of property tensors of rank <5 that
      follow from the Neumann principle for the point groups describing quasicrystals
      can easily be deduced from the restrictions for the point groups describing
      ordinary crystals. For octagonal and dodecagonal point groups, this is true even
      for property tensors of rank<8 and <12, respectively. The results derived in a
      number of papers for various physical properties of quasicrystals with certain
      point-group symmetries are generalized to all quasicrystal point groups, and it
      is shown that the results become more lucid if the classification of quasicrystal
      point groups with a principal axis into pentagonal, decagonal, octagonal and
      dodecagonal ones is done appropriately. A comparison with other approaches shows
      that applying the Neumann principle for the point groups describing quasicrystals
      yields the form of the so-called phonon part of the tensor under consideration.
      Connections between the restrictions valid for property tensors of arbitrary rank
      are given for general Heesch-Shubnikov point groups in three dimensions.

PMID- 17435292
TI  - Size-dependent interbranch peculiarities of X-ray extinction in strongly bent
      crystals.
AB  - X-ray diffraction from homogeneously bent crystals is studied within the
      interbranch resonance concept for large gradient. It is shown that strong
      deformations lead to an interbranch phase modulation of the transmitted and
      diffracted waves. It is predicted that prominent extinction effects occur due to
      the interbranch phase changes. These features are very sensitive to the crystal
      thickness, so that changes of the order of the interbranch extinction length can
      affect considerably the rocking-curve structure. Numerical calculations of the
      diffracted intensity are carried out to illustrate this.

PMID- 17435293
TI  - Overlooked problems in manifold twins: twin misfit in zero-obliquity TLQS
      twinning and twin index calculation.
AB  - It is shown that the twin index n calculated, according to Friedel, as a function
      of the indices (hkl) and [uvw] of the lattice plane and lattice direction
      defining the cell of the twin lattice applies only to twofold twins, i.e. twins
      where the twin element is of order 2. For manifold twins, where the twin
      operation is a three-, four- or sixfold (direct or inverse) rotation, it is shown
      that the generalized formula becomes n=NXi/xi, where N is the number of lattice
      planes of the (hkl) family passing within the cell of the twin lattice, Xi the
      two-dimensional coincidence index for a plane of the (hkl) family and xi the
      number of planes out of N of that family that are partially restored by the twin
      operation. The existence of twin lattice quasi-symmetry (TLQS) twins with zero
      obliquity in manifold twins leads to the introduction of a new parameter as a
      general measure of the pseudo-symmetry of TLQS rotation twins: the twin misfit
      delta, defined as the distance between the first nodes along the two shortest
      directions in the plane of LT (quasi-)perpendicular to the twin axes that are
      quasi-restored by the twin operation. Taking the example of staurolite twins,
      several inconsistencies in the treatment of manifold twins are pointed out.

PMID- 17435298
TI  - The Beamline X28C of the Center for Synchrotron Biosciences: a national resource
      for biomolecular structure and dynamics experiments using synchrotron
      footprinting.
AB  - Structural mapping of proteins and nucleic acids with high resolution in solution
      is of critical importance for understanding their biological function. A wide
      range of footprinting technologies have been developed over the last ten years to
      address this need. Beamline X28C, a white-beam X-ray source at the National
      Synchrotron Light Source of Brookhaven National Laboratory, functions as a
      platform for synchrotron footprinting research and further technology development
      in this growing field. An expanding set of user groups utilize this national
      resource funded by the National Institute of Biomedical Imaging and
      Bioengineering of the National Institutes of Health. The facility is operated by
      the Center for Synchrotron Biosciences and the Center for Proteomics of Case
      Western Reserve University. The facility includes instrumentation suitable for
      conducting both steady-state and millisecond time-resolved footprinting
      experiments based on the production of hydroxyl radicals by X-rays. Footprinting
      studies of nucleic acids are routinely conducted with X-ray exposures of tens of
      milliseconds, which include studies of nucleic acid folding and their
      interactions with proteins. This technology can also be used to study protein
      structure and dynamics in solution as well as protein-protein interactions in
      large macromolecular complexes. This article provides an overview of the X28C
      beamline technology and defines protocols for its adoption at other synchrotron
      facilities. Lastly, several examples of published results provide illustrations
      of the kinds of experiments likely to be successful using these approaches.

PMID- 17435299
TI  - The small-angle and wide-angle X-ray scattering set-up at beamline BL9 of DELTA.
AB  - The multi-purpose experimental endstation of beamline BL9 at the Dortmund
      Electron Accelerator (DELTA) is dedicated to diffraction experiments in grazing
      incidence geometry, reflectivity and powder diffraction measurements. Moreover,
      fluorescence analysis and inelastic X-ray scattering experiments can be
      performed. Recently, a new set-up for small-angle and wide-angle X-ray scattering
      utilizing detection by means of an image-plate scanner was installed and is
      described in detail here. First small-angle X-ray scattering experiments on
      aqueous solutions of lysozyme with different cosolvents and of staphylococcal
      nuclease are discussed. The application of the set-up for texture analysis is
      emphasized and a study of the crystallographic texture of natural bio
      nanocomposites, using lobster and crab cuticles as model materials, is presented.

PMID- 17435300
TI  - Zr and Ba edge phenomena in the scintillation intensity of fluorozirconate-based
      glass-ceramic X-ray detectors.
AB  - The energy-dependent scintillation intensity of Eu-doped fluorozirconate glass
      ceramic X-ray detectors has been investigated in the energy range from 10 to 40
      keV. The experiments were performed at the Advanced Photon Source, Argonne
      National Laboratory, USA. The glass ceramics are based on Eu-doped
      fluorozirconate glasses, which were additionally doped with chlorine to initiate
      the nucleation of BaCl(2) nanocrystals therein. The X-ray excited scintillation
      is mainly due to the 5d-4f transition of Eu(2+) embedded in the BaCl(2)
      nanocrystals; Eu(2+) in the glass does not luminesce. Upon appropriate annealing
      the nanocrystals grow and undergo a phase transition from a hexagonal to an
      orthorhombic phase of BaCl(2). The scintillation intensity is investigated as a
      function of the X-ray energy, particle size and structure of the embedded
      nanocrystals. The scintillation intensity versus X-ray energy dependence shows
      that the intensity is inversely proportional to the photoelectric absorption of
      the material, i.e. the more photoelectric absorption the less scintillation. At
      18 and 37.4 keV a significant decrease in the scintillation intensity can be
      observed; this energy corresponds to the K-edge of Zr and Ba, respectively. The
      glass matrix as well as the structure and size of the embedded nanocrystals have
      an influence on the scintillation properties of the glass ceramics.

PMID- 17435301
TI  - Element-selective X-ray detected magnetic resonance: a novel application of
      synchrotron radiation.
AB  - X-ray detected magnetic resonance (XDMR) is a new element-selective spectroscopy
      in which X-ray magnetic circular dichroism is used to probe the resonant
      precession of spin and orbital magnetization components when a strong microwave
      pump field is applied perpendicularly to the static bias field. Experimental
      configurations suitable for detecting the very weak XDMR signal are compared.
      XDMR signatures were measured in yttrium iron garnet and related thin films on
      exciting not only the iron K-edge but also the yttrium at diamagnetic sites.
      These measurements are shown to yield unique information regarding the wide-angle
      precession of induced magnetization components involving either orbital p
      projected densities of states at the iron sites, or spin polarized d-projected
      densities of states at the yttrium sites. Extending XDMR measurements into the
      millimeter wave range would make it possible to study paramagnetic systems
      routinely and investigate optical modes as well as acoustic modes in
      ferrimagnetic/antiferromagnetic systems.

PMID- 17435302
TI  - Application of glancing-emergent-angle fluorescence for polarized XAFS studies of
      single crystals.
AB  - X-ray absorption fine-structure (XAFS) data were obtained for the V K-edge for a
      series of anisotropic single crystals of (Cr(x)V(1-x))(2)O(3). The data and the
      results were compared for the as-prepared bulk single crystals (measured in
      fluorescence in two different orientations) and those ground to powder (measured
      in transmission). For the bulk single crystals, the glancing-emergent-angle (GEA)
      method was used to minimize fluorescence distortion. The reliability of the GEA
      technique was tested by comparing the polarization-weighted single-crystal XAFS
      data with the experimental powder data. These data were found to be in excellent
      agreement throughout the entire energy range. Thus, it was possible to reliably
      measure individual V-V contributions parallel and perpendicular to the c axis of
      the single crystals, i.e. those unavailable by powder data XAFS analysis. These
      experiments demonstrate that GEA is a premiere method for non-destructive high
      photon-count in situ studies of local structure in bulk single crystals.

PMID- 17435303
TI  - Performance of a fuel cell optimized for in situX-ray absorption experiments.
AB  - A commercial fuel cell has been successfully modified to carry out X-ray
      absorption spectroscopy (XAS) measurements under optimized in operando
      conditions. The design is conceived for the performance of XAS experiments in
      transmission mode over a wide range of X-ray energies above 6 keV, owing to the
      reduced absorption of the cell. The wide angular aperture allows the collection
      of XAS in fluorescence mode and of X-ray diffraction patterns when needed.
      Details of the design of the cell and its performances are given. The quality of
      the extended X-ray absorption fine-structure spectra under working conditions has
      been verified at the ESRF and ELETTRA synchrotron radiation facilities, showing
      that relatively fast and low-noise transmission measurements on electrodes over a
      wide range of catalyst concentrations and energies are feasible.

PMID- 17435304
TI  - Computed tomography imaging of the neuronal structure of Drosophila brain.
AB  - The neural circuit of the central nervous system (CNS) primarily determines brain
      functions and, as a consequence, controls animal behavior. This paper describes
      an X-ray microtomographic analysis of the Drosophila larvae CNS, visualizing the
      neural network embedded in the three-dimensional structure of the nerve tissue.
      In fluorescence confocal microscopy, absorbance at emission or excitation
      wavelengths interferes with the fluorescence detection. In contrast, transparency
      of the nerve tissue to hard X-rays enables tomographic analysis of the intact CNS
      without sectioning. Yet the nerve tissue is composed of light elements that give
      little contrast in a hard X-ray transmission image. The contrast was enhanced by
      staining neuropils in the CNS with metal elements. The obtained structure
      revealed the internal architecture of the CNS. This metal-staining
      microtomographic analysis can be applied to any nerve tissues, thereby shedding
      light on the underlying structural basis of neural functions.

PMID- 17435305
TI  - Small-angle pump-probe studies of photoexcited nanoparticles.
AB  - X-ray scattering experiments on femtosecond laser-excited gold nanoparticle
      suspensions are presented. It is shown that the time-resolved pump-probe
      technique using the X-ray pulse structure at synchrotron sources is capable of
      resolving structural dynamics on the nanometer scale to high precision. The
      estimation of X-ray flux density allows the projection of experiments on an X-ray
      free-electron laser probing single nanoparticles in a one-shot exposure.

PMID- 17435306
TI  - A kHz heat-load shutter for white-beam experiments at synchrotron sources.
AB  - A heat-load shutter capable of frequencies from one to several tens of kHz and
      window times from 10 micros up to 1 ms is described. In the current configuration
      the water-cooled shutter absorbs approximately 99% of the heat generated by the
      white beam. It has been successfully used for extended periods synchronized with
      a Julich pulse-selector operating at 946 Hz. The temperature of the pulse
      selector remained constant during a three-day continuous operation. Flexibility
      is provided by the interchangeability of the chopper disc.

PMID- 17435308
TI  - Negative databases.

PMID- 17435309
TI  - Who really wants to save the apes?

PMID- 17435310
TI  - The value of comparative genomics in understanding mycobacterial virulence:
      Mycobacterium tuberculosis H37Ra genome sequencing - a worthwhile endeavour.

PMID- 17435311
TI  - Successful beyond expectation: David Perkins's research with chromosome
      rearrangements in Neurospora.

PMID- 17435312
TI  - Beadle's progeny: innocence rewarded, innocence lost.

PMID- 17435313
TI  - Living in a physical world X. Pumping fluids through conduits.

PMID- 17435314
TI  - What history tells us VIII. The progressive construction of a mechanism for prion
      diseases.

PMID- 17435315
TI  - BOXTO as a real-time thermal cycling reporter dye.
AB  - The unsymmetrical cyanine dyes BOXTO (4-[6-(benzoxazole-2-yl-(3-methyl-)-2,3
      dihydro-(benzo-1,3-thiazole)-2- methylidene)]-1-methyl-quinolinium chloride)and
      its positive divalent derivative BOXTO-PRO (4-[(3-methyl-6-(benzoxazole-2-yl)-2,3
      dihydro-(benzo-1,3-thiazole)-2-methylidene)]-1-(3-trimethylammonium-propyl)
      quinolinium dibromide) were studied as real-time PCR reporting fluorescent dyes
      and compared to SYBR GREEN I (SG)(2-[N- (3-dimethylaminopropyl)-N-propylamino] -4
      [2,3-dihydro-3-methyl-(benzo-1,3-thiazol-2-yl)-methylidene]-1-phenyl-
      quinolinium).Unmodified BOXTO showed no inhibitory effects on real-time PCR,while
      BOXTO-PRO showed complete inhibition. Sufficient fluorescent signal was acquired
      when 0.5-1.0 meu M BOXTO was used with RotorGene and iCycler
      platforms.Statistical analysis showed that there is no significant difference
      between the efficiency and dynamic range of BOXTO and SG.BOXTO stock solution
      (1.5 mM) was stable at -20 degree C for more than one year and 40 meu M BOXTO
      solution was more stable than 5x SG when both were stored at 4 degree C for 45
      days.

PMID- 17435316
TI  - cDNA cloning and expression analysis of a mannose-binding lectin from Pinellia
      pedatisecta.
AB  - Pinellia pedatisecta agglutinin (PPA)is a very basic protein that accumulates in
      the tuber of P.pedatisecta .PPA is a hetero-tetramer protein of 40 kDa,composed
      of two polypeptide chains A (about 12 kDa)and two polypeptides chains B (about 12
      kDa).The full-length cDNA of PPA was cloned from P.pedatisecta using SMART RACE
      PCR technology; it was 1146 bp and contained a 771 bp open reading frame
      (ORF)encoding a lectin precursor of 256 amino acid residues with a 24 amino acid
      signal peptide.The PPA precursor contained 3 mannose-binding sites (QXDXNXVXY)
      and two conserved domains of 43% identity,PPA-DOM 1 (polypeptides A)and PPA-DOM 2
      (polypeptides B).PPA shared varying identities,ranging from 40% to 85%,with
      mannose-binding lectins from other species of plant families such as Araceae,
      Alliaceae, Iridaceae, Liliaceae, Amaryllidaceae and Bromeliaceae. Southern blot
      analysis indicated that ppa belonged to a multi-copy gene family. Expression
      pattern analysis revealed that ppa expressed in most tested tissues, with high
      expression being found in spadix,spathe and tuber.Cloning of the ppa gene not
      only provides a basis for further investigation of its structure,expression and
      regulatory mechanism,but also enables us to test its potential role in
      controlling pests and fungal diseases by transferring the gene into plants in the
      future.

PMID- 17435317
TI  - Antisense expression of a gene encoding a calcium-binding protein in transgenic
      tobacco leads to altered morphology and enhanced chlorophyll.
AB  - Entamoeba histolytica contains a novel calcium-binding protein like
      calmodulin,which was discovered earlier,and we have reported the presence of its
      homologue(s)and a dependent protein kinase in plants.To understand the functions
      of these in plants,a cDNA encoding a calcium-binding protein isolated from
      Entamoeba histolytica (EhCaBP)was cloned into vector pBI121 in antisense
      orientation and transgenic tobacco plants were raised.These plants showed
      variation in several phenotypic characters,of which two distinct features,more
      greenness and leaf thickness,were inherited in subsequent generations.The
      increase in the level of total chlorophyll in different plants ranged from 60% to
      70%.There was no major change in chloroplast structure and in the protein level
      of D1,D2,LHCP and RuBP carboxylase.These morphological changes were not seen in
      antisense calmodulin transgenic tobacco plants,nor was the calmodulin level
      altered in EhCaBP antisense plants.

PMID- 17435318
TI  - A homologue of the defender against the apoptotic death gene (dad1 )in UV-exposed
      Chlamydomonas cells is downregulated with the onset of programmed cell death.
AB  - We report here the isolation of a homologue of the potential anti-apoptotic gene,
      defender against apoptotic death (dad1 )from Chlamydomonas reinhardtii
      cells.Using polymerase chain reaction (PCR),we investigated its expression in the
      execution process of programmed cell death (PCD)in UV-C exposed dying
      C.reinhardtii cells.Reverse- transcriptase (RT)-PCR showed that C.reinhardtii
      dad1 amplification was drastically reduced in UV-C exposed dying C.reinhardtii
      cells.We connect the downregulation of dad1 with the upregulation of apoptosis
      protease activating factor-1 (APAF-1)and the physiological changes that occur in
      C.reinhardtii cells upon exposure to 12 J/m 2 UV-C in order to show a reciprocal
      relationship between proapoptotic and inhibitor of apoptosis factors.The temporal
      changes indicate a correlation between the onset of cell death and dad1
      downregulation.The sequence of the PCR product of the cDNA encoding the dad1
      homologue was aligned with the annotated dad1 (C_20215)from the Chlamydomonas
      database (http://genome.jgi
      psf.org:8080/annotator/servlet/jgi.annotation.Annotation?pDb=chlre2);
      Annotation?pDb=chlre2 );this sequence was found to show 100% identity,both at the
      nucleotide and amino acid level. The 327 bp transcript showed an open reading
      frame of 87 amino acid residues.The deduced amino acid sequence of the putative
      C.reinhardtii DAD1 homologue showed 54% identity with Oryza sativa, 56 identity
      with Drosophila melanogaster, 66% identity with Xenopus laevis, and 64% identity
      with Homo sapiens,Sus scrofa,Gallus gallus,Rattus norvegicus and Mus musculus.

PMID- 17435319
TI  - Electrochemical investigation of the effect of some organic phosphates on
      haemoglobin.
AB  - The effects of DPG,IHP,GTP,GDP and GMP on the structure and stability of
      haemoglobin were electrochemically investigated with an iodide-modified silver
      electrode in 0.01 M KNO 3 at pH 7.0.Anodic and cathodic peaks of haemoglobin were
      observed at 250 mV and 12 mV with a formal potential value of 133 mV
      vs.Ag/AgCl.The effects of different concentrations of DPG,IHP,GTP,GDP and GMP on
      the anaerobic redox reaction were determined. The results showed that DPG and IHP
      can lead to a positive shift in the reduction peak of haemoglobin,indicating that
      the oxidation peak shift of haemoglobin was small as a result of stabilization of
      the reduced state and destabilization of the R-like state of haemoglobin.GTP
      elicited a more positive shift in the cathodic and anodic peaks of haemoglobin at
      a higher concentration,signifying that it has a low-affinity binding site on
      haemoglobin.The positive shift of the cathodic and anodic peaks revealed a slight
      variation in the structure and indicated the unfolding of haemoglobin in the
      presence of high concentrations of GTP.Our study also showed that GDP and GMP did
      not cause significant shift the cathodic and anodic peaks of haemoglobin even at
      high concentrations,refuting the existence of specific GDP-and GMP-binding sites
      on the protein.Moreover,the iodide-modified silver electrode method proved to be
      easy and useful in investigating the effects of ligands or other effectors on
      haemoglobin in solution.

PMID- 17435320
TI  - Dihydroxyoctadecamonoenoate esters inhibit the neutrophil respiratory burst.
AB  - The leukotoxins [9(10)-and 12(13)-EpOME] are produced by activated inflammatory
      leukocytes such as neutrophils. High EpOME levels are observed in disorders such
      as acute respiratory distress syndrome and in patients with extensive
      burns.Although the physiological significance of the EpOMEs remains poorly
      understood,in some systems, the EpOMEs act as a protoxin,with their corresponding
      epoxide hydrolase metabolites,9,10-and 12,13-DiHOME, specifically exerting
      toxicity.Both the EpOMEs and the DiHOMEs were also recently shown to have
      neutrophil chemotactic activity.We evaluated whether the neutrophil respiratory
      burst,a surge of oxidant production thought to play an important role in limiting
      certain bacterial and fungal infections,is modulated by members of the EpOME
      metabolic pathway.We present evidence that the DiHOMEs suppress the neutrophil
      respiratory burst by a mechanism distinct from that of respiratory burst
      inhibitors such as cyclosporin H or lipoxin A4,which inhibit multiple aspects of
      neutrophil activation.

PMID- 17435321
TI  - Age-related decrease in rod bipolar cell density of the human retina: an
      immunohistochemical study.
AB  - During normal ageing, the rods (and other neurones) undergo a significant
      decrease in density in the human retina from the fourth decade of life
      onward.Since the rods synapse with the rod bipolar cells in the outer plexiform
      layer, a decline in rod density (mainly due to death)may ultimately cause an
      associated decline of the neurones which,like the rod bipolar cells,are connected
      to them.The rod bipolar cells are selectively stained with antibodies to protein
      kinase C-alpha.This study examined if rod bipolar cell density changes with
      ageing of the retina, utilizing donor human eyes (age: 6-91 years).The retinas
      were fixed and their temporal parts from the macula to the mid-periphery
      sectioned and processed for protein kinase C-alpha immunohistochemistry.The
      density of the immunopositive rod bipolar cells was estimated in the mid
      peripheral retina (eccentricity: 3-5 mm)along the horizontal temporal axis.The
      results show that while there is little change in the density of the rod bipolar
      cells from 6 to 35 years (2.2%), the decline during the period from 35 to 62
      years is about 21% and between seventh and tenth decades,it is approximately 27%.

PMID- 17435322
TI  - Chondroprotective potential of root extracts of Withania somnifera in
      osteoarthritis.
AB  - This is the first report describing two novel chondroprotective activities of
      aqueous extracts of Withania somnifera root powder.First,these extracts had a
      statistically significant,short-term chondroprotective effect on damaged human
      osteoarthritic cartilage matrix in 50% of the patients tested. Second,these
      extracts caused a significant and reproducible inhibition of the gelatinase
      activity of collagenase type 2 enzyme in vitro.

PMID- 17435324
TI  - A model for cell type localization in the migrating slug of Dictyostelium
      discoideum based on differential chemotactic sensitivity to cAMP and differential
      sensitivity to suppression of chemotaxis by ammonia.
AB  - The three basic cell types in the migrating slug of Dictyostelium discoideum show
      differential chemotactic response to cyclic AMP (cAMP) and differential
      sensitivity to suppression of the chemotaxis by ammonia.The values of these
      parameters indicate a progressive maturation of chemotactic properties during the
      transdifferentiation of slug cell types.We present a model that explains the
      localization of the three cell types within the slug based on these chemotactic
      differences and on the maturation of their chemotactic properties.

PMID- 17435323
TI  - Programmed cell death in the larval salivary glands of Apis mellifera
      (Hymenoptera, Apidae).
AB  - The morphological and histochemical features of degeneration in honeybee (Apis
      mellifera) salivary glands were investigated in 5th instar larvae and in the pre
      pupal period. The distribution and activity patterns of acid phosphatase enzyme
      were also analysed. As a routine,the larval salivary glands were fixed and
      processed for light microscopy and transmission electron microscopy.Tissue
      sections were subsequently stained with haematoxylin -eosin,bromophenol
      blue,silver,or a variant of the critical electrolyte concentration (CEC)
      method.Ultrathin sections were contrasted with uranyl acetate and lead
      citrate.Glands were processed for the histochemical and cytochemical localization
      of acid phosphatase,as well as biochemical assay to detect its activity pattern.
      Acid phosphatase activity was histochemically detected in all the salivary glands
      analysed.The cytochemical results showed acid phosphatase in vesicles, Golgi
      apparatus and lysosomes during the secretory phase and,additionally, in
      autophagic structures and luminal secretion during the degenerative phase. These
      findings were in agreement with the biochemical assay. At the end of the 5th
      instar, the glandular cells had a vacuolated cytoplasm and pyknotic nuclei, and
      epithelial cells were shed into the glandular lumen.The transition phase from the
      5th instar to the pre-pupal period was characterized by intense vacuolation of
      the basal cytoplasm and release of parts of the cytoplasm into the lumen by
      apical blebbing; these blebs contained cytoplasmic RNA, rough endoplasmic
      reticule and, occasionally, nuclear material. In the pre-pupal phase, the
      glandular epithelium showed progressive degeneration so that at the end of this
      phase only nuclei and remnants of the cytoplasm were observed.The nuclei were
      pyknotic,with peripheral chromatin and blebs. The gland remained in the
      haemolymph and was recycled during metamorphosis. The programmed cell death in
      this gland represented a morphological form intermediate between apoptosis and
      autophagy.

PMID- 17435325
TI  - Electroantennogram responses of the potato tuber moth, Phthorimaea operculella
      (Lepidoptera; Gelichiidae)to plant volatiles.
AB  - Electroantennograms (EAGs)were recorded from males and females of the potato
      tuber moth,Phthorimaea operculella in response to a broad range of plant volatile
      compounds belonging to diverse chemical classes.The responses to 27 compounds
      were evaluated,which indicated significant differences in EAGs between chemicals
      as well as between sexes.The fatty acid derivatives comprising essentially green
      leaf volatile components elicited significantly greater responses in females.The
      response profile of males was,in general,lower than that of females.EAG responses
      to the oxygenated and hydrocarbon monoterpenes were lower in both males and
      females.Dose -response studies indicate differences in response between the sexes
      and concentrations,suggesting the existence of sexual dimorphism. Compounds
      belonging to the fatty acid derivatives class appear to be important for an
      oligophagous pest such as the potato tuber moth and the findings are discussed in
      relation to host plant selection in this species.

PMID- 17435326
TI  - A mechanical model of wing and theoretical estimate of taper factor for three
      gliding birds.
AB  - We tested a mechanical model of wing,which was constructed using the measurements
      of wingspan and wing area taken from three species of gliding birds.In this
      model,we estimated the taper factors of the wings for jackdaw (Corrus monedula),
      Harris' hawk (Parabuteo unicinctas) and Lagger falcon (Falco jugger) as 1.8, 1.5
      and 1.8,respectively. Likewise, by using the data linear regression and curve
      estimation method,as well as estimating the taper factors and the angle between
      the humerus and the body, we calculated the relationship between wingspan,wing
      area and the speed necessary to meet the aerodynamic requirements of sustained
      flight.In addition,we calculated the relationship between the speed,wing area and
      wingspan for a specific angle between the humerus and the body over the range of
      stall speed to maximum speed of gliding flight.We then compared the results for
      these three species of gliding birds. These comparisons suggest that the
      aerodynamic characteristics of Harris' hawk wings are similar to those of the
      falcon but different from those of the jackdaw.This paper also presents two
      simple equations to estimate the minimum angle between the humerus and the body
      as well as the minimum span ratio of a bird in gliding flight.

PMID- 17435327
TI  - Heterotrophic free-living and particle-bound bacterial cell size in the river
      Cauvery and its downstream tributaries.
AB  - This is the first comprehensive study on planktonic heterotrophic bacterial cell
      size in the river Cauvery and its important tributaries in Karnataka State,
      India. The initial hypothesis that the mean cell size of planktonic heterotrophic
      bacteria in the four tributaries are markedly different from each other and also
      from that in the main river Cauvery was rejected, because all five watercourses
      showed similar planktonic heterotrophic bacterial cell size. Examination of the
      correlation between mean heterotrophic bacterial cell size and environmental
      variables showed four correlations in the river Arkavathy and two in the river
      Shimsha. Regression analysis revealed that 18%of the variation in mean
      heterotrophic free-living bacterial cell size was due to biological oxygen demand
      (BOD)in the river Arkavathy, 11% due to surface water velocity (SWV)in the river
      Cauvery and 11% due to temperature in the river Kapila. Heterotrophic particle
      bound bacterial cell size variation was 28% due to chloride and BOD in the river
      Arkavathy, 11% due to conductivity in the river Kapila and 8% due to calcium in
      the river Cauvery. This type of relationship between heterotrophic bacterial cell
      size and environmental variables suggests that,though the mean heterotrophic
      bacterial cell size was similar in all the five water courses, different sets of
      environmental variables apparently control the heterotrophic bacterial cell size
      in the various water bodies studied in this investigation. The possible cause for
      this environmental (bottom -up) control is discussed.

PMID- 17435328
TI  - Contribution of root to soil respiration and carbon balance in disturbed and
      undisturbed grassland communities, northeast China.
AB  - Changes in the composition of plant species induced by grassland degradation may
      alter soil respiration rates and decrease carbon sequestration; however, few
      studies in this area have been conducted. We used net primary productivity
      (NPP),microbial biomass carbon (MBC), and soil organic carbon (SOC)to examine the
      changes in soil respiration and carbon balance in two Chinese temperate grassland
      communities dominated by Leymus chinensis (undisturbed community; Community 1)and
      Puccinellia tenuiflora (degraded community; Community 2), respectively. Soil
      respiration varied from 2.5 to 11.9 g CO 2 m ;-2 d;-1 and from 1.5 to 9.3 g CO2
      m;-2 d;-1, and the contribution of root respiration to total soil respiration
      from 38% to 76% and from 25% to 72% in Communities 1 and 2,respectively. During
      the growing season (May-September), soil respiration, shoot biomass, live root
      biomass, MBC and SOC in Community 2 decreased by 28%,39%,45%,55% and
      29%,respectively, compared to those in Community 1.The considerably lower net
      ecosystem productivity in Community 2 than in Community 1 (104.56 vs. 224.73 g C
      m;-2 yr;-1) suggests that the degradation has significantly decreased carbon
      sequestration of the ecosystems.

PMID- 17435329
TI  - Detection without deflection? A hypothesis for direct sensing of sound pressure
      by hair cells.
AB  - It is widely thought that organisms detect sound by sensing the deflection of
      hair-like projections, the stereocilia, at the apex of hair cells. In the case of
      mammals, the standard interpretation is that hair cells in the cochlea respond to
      deflection of stereocilia induced by motion generated by a hydrodynamic
      travelling wave. But in the light of persistent anomalies, an alternative
      hypothesis seems to have some merit: that sensing cells (in particular the outer
      hair cells) may, at least at low intensities, be reacting to a different stimulus
      - the rapid pressure wave that sweeps through the cochlear fluids at the speed of
      sound in water. This would explain why fast responses are sometimes seen before
      the peak of the travelling wave. Yet how could cells directly sense fluid
      pressure? Here, a model is constructed of the outer hair cell as a pressure
      vessel able to sense pressure variations across its cuticular pore, and this
      'fontanelle' model, based on the sensing action of the basal body at this
      compliant spot, could explain the observed anomalies. Moreover, the fontanelle
      model can be applied to a wide range of other organisms, suggesting that direct
      pressure detection is a general mode of sensing complementary to stereociliar
      displacement.

PMID- 17435330
TI  - Molecular mechanism of insulin resistance.
AB  - Free fatty acids are known to play a key role in promoting loss of insulin
      sensitivity,thereby causing insulin resistance and type 2 diabetes.However,the
      underlying mechanism involved is still unclear.In searching for the cause of the
      mechanism,it has been found that palmitate inhibits insulin receptor (IR)gene
      expression,leading to a reduced amount of IR protein in insulin target cells.
      PDK1-independent phosphorylation of PKC(eta) causes this reduction in insulin
      receptor gene expression.One of the pathways through which fatty acid can induce
      insulin resistance in insulin target cells is suggested by these studies.We
      provide an overview of this important area,emphasizing the current status.

PMID- 17435331
TI  - Polyphenism in insects and the juvenile hormone.

PMID- 17435332
TI  - The stability of ecosystems: a brief overview of the paradox of enrichment.
AB  - In theory, enrichment of resource in a predator-prey model leads to
      destabilization of the system,thereby collapsing the trophic interaction,a
      phenomenon referred to as "the paradox of enrichment". After it was first pro
      posed by Rosenzweig (1971), a number of subsequent studies were carried out on
      this dilemma over many decades. In this article, we review these theoretical and
      experimental works and give a brief overview of the proposed solutions to the
      paradox. The mechanisms that have been discussed are modifications of simple
      predator -prey models in the presence of prey that is inedible, invulnerable,
      unpalatable and toxic. Another class of mechanisms includes an incorporation of a
      ratio-dependent functional form,inducible defence of prey and density-dependent
      mortality of the predator. Moreover, we find a third set of explanations based on
      complex population dynamics including chaos in space and time. We conclude
      that,although any one of the various mechanisms proposed so far might potentially
      prevent destabilization of the predator-prey dynamics following enrichment, in
      nature different mechanisms may combine to cause stability, even when a system is
      enriched. The exact mechanisms,which may differ among systems,need to be
      disentangled through extensive field studies and laboratory experiments coupled
      with realistic theoretical models.

PMID- 17435333
TI  - [Lentiviral vector-mediated in vivo SERCA2a gene transfer improved cardiac
      function and remodeling of failing heart induced by myocardial infarction in the
      rat].

PMID- 17435334
TI  - [Involvement of Fyn tyrosine kinase and membrane rafts in the signal transduction
      in Ca2+-sensitization of vascular smooth muscle contraction].

PMID- 17435335
TI  - [Identification of PI3K-C2alpha as the mediator of Ca2+-induced Rho activation
      and MLC phosphatase inhibition].

PMID- 17435336
TI  - [Novel signaling mechanism of angiotensin II type 2 receptor].

PMID- 17435337
TI  - [Na+/Ca2+ exchanger (NCX1) and cardiovascular disease].

PMID- 17435338
TI  - [Research and developmental strategy of anti-dyslipidemic agents].

PMID- 17435339
TI  - [Candidate drugs for non-alcoholic steatohepatitis (NASH)].

PMID- 17435340
TI  - [High throughput screening in the process of drug discovery].

PMID- 17435341
TI  - [Does high throughput screening work?].

PMID- 17435342
TI  - [Pharmacological properties and clinical efficacy of entecavir monohydrate
      (Baraclude Tablet 0.5 mg), an anti-HBV drug].

PMID- 17435343
TI  - [A novel antiepileptic, gabapentin (GABAPEN)].

PMID- 17435344
TI  - A 350-S recovery period does not necessarily allow complete recovery of peak
      power output during repeated cycling sprints.
AB  - The aim of this study was to determine whether a 350-s recovery period allows
      recovery of peak power output (PPO) to its initial value under the condition of a
      blood lactate (La) concentration higher than 10 mmol.L-1 during repeated cycling
      sprints (RCS). RCS (10x10-s cycling sprints) were performed under two conditions.
      Under one condition, the recovery period of RCS was fixed at 35 s (RCS35), and
      under the other condition, a 350-s recovery period was set before the 5th and 9th
      sets, and a 35-s recovery period was set before the other sets (RCScomb). In
      RCScomb, PPO in the 5th set recovered to that in the 1st set, but PPO in the 9th
      set did not. Under both conditions, blood La concentration progressively
      increased and reached approximately 14 mmol.L-1 at the end of the RCS. In
      RCScomb, VO2 immediately before the 5th set was not significantly different from
      that immediately before the 9th set. Mean power frequency (MPF) values estimated
      by a surface electromyogram from the vastus lateralis in the 5th and 9th sets
      were significantly higher in RCScomb than in RCS35. In conclusion, a 350-s
      recovery period does not allow recovery of PPO to its initial value under the
      condition of a blood La concentration of 14 mmol.L-1 during RCS.

PMID- 17435345
TI  - Physical fitness and anthropometrical profile of the Brazilian male judo team.
AB  - The present study had as objectives (1) to compare the morphological and
      functional characteristics of the male judo players of the Brazilian Team A (n=7)
      with the judo players of Teams B and C (reserves; n=15), and (2) to verify the
      association between the variables measured. Thus, 22 athletes from the seven
      Olympic weight categories were submitted to: a body composition evaluation (body
      mass, height, ten skinfolds, eight circumferences, three bone diameters and
      percent body fat estimation); the Special Judo Fitness Test (SJFT); maximal
      strength tests (one repetition-maximum, 1 RM, in bench press, row, and squat);
      and the Cooper test. One-way analysis of covariance was used to compare the
      groups. The relationships between variables were determined by the Pearson
      coefficient correlation. The significance level was fixed at 5%. No significant
      difference was found in any variable between them. The main significant
      correlations observed were between the following variables: VO2max and number of
      throws in the SJFT (r=0.79); percent body fat and estimated VO2max (r=-0.83) and
      number of throws in the SJFT (r=-0.70); chest circumference and bench press 1 RM
      (r=0.90) and in the row (r=0.80); and thigh circumference and squat 1 RM
      (r=0.86). However, there was no significant correlation between circumferences
      and 1 RM/kg of body mass. According to these results the main conclusions are:
      (1) the physical variables measured do not discriminate performance when analysis
      is directed to the best athletes; (2) a higher percent body fat is negatively
      correlated with performance in activities with body mass locomotion (Cooper test
      and the SJFT); (3) judo players with higher aerobic power performed better in
      high-intensity intermittent exercise; (4) judo players with bigger circumferences
      present bigger absolute maximal strength.

PMID- 17435346
TI  - The influence of visual display terminal use on the physical and mental
      conditions of administrative staff in Japan.
AB  - Visual display terminals (VDT) are standard equipment for many office workers.
      Their use, however, may increase the risk of developing adverse conditions
      related to vision, the musculoskeletal system, and mental health. We carried out
      a survey among 3070 workers aged 18 to 67 years (mean, 39.9 years) at a
      prefectural administrative office, in which 76% of subjects were visual display
      terminal (VDT) users. We examined the relationship between duration of daily VDT
      use and eyestrain, neck or upper extremity pain, back pain, and mental health,
      and estimated the effect of breaks and rest during VDT work on these symptoms.
      The 12-item General Health Questionnaire (GHQ-12: total scores ranged from 0 to
      12) was used to identify potential poor mental health status, and subjects with 4
      or more were considered to have symptoms of psychological distress. Seventeen
      percent of subjects reported eyestrain, 19.1% reported upper extremity pain,
      11.6% reported back pain, and 17% of subjects had GHQ-12 scores of 4 or higher.
      Logistic regression analysis showed that duration of daily VDT use and lack of
      breaks and rest during VDT work were significantly associated with eyestrain,
      neck or upper extremity pain, back pain, and psychological distress. In order to
      protect users from the adverse effects associated with VDT work, reducing daily
      VDT exposure, taking breaks, and rest during VDT work are important.

PMID- 17435347
TI  - Physical anthropology and ethnicity in Asia: the transition from anthropometry to
      genome-based studies.
AB  - Initial physical anthropology studies into ethnic diversity were largely
      dependent on comparative whole body and craniometric measurements, and through
      time assessments of ethnic diversity based on these measures exhibited increasing
      statistical sophistication. Since the 1990s, in Asia as elsewhere in the world,
      human diversity studies have increasingly utilized DNA-based analyses, with Y
      chromosome and mtDNA markers providing complementary perspectives on the origins
      and gene pool structures of different ethnic groups. This approach is illustrated
      in a study of population genetic structure in PR China, in which DNA samples from
      the Han majority and eight ethnic minorities were analyzed. The Y-chromosome and
      mtDNA data showed multiple paternal geographical and ethnic origins but
      restricted maternal ancestries. However, interpretive problems were apparent in
      the definition of a number of the ethnic study populations, which appear to
      reflect political as well as genetic influences. In all anthropological studies,
      whether based on anthropometry or genomic analysis, unambiguous and appropriate
      community identification is a prerequisite.

PMID- 17435348
TI  - Benefits of nature: what we are learning about why people respond to nature.
AB  - People have positive aesthetic, emotional, and physiological responses to nature.
      Why is this so? The "savanna hypothesis," proposed by Gordon Orians, predicts
      that some human responses are based on innate knowledge of productive human
      habitats. To test this, researchers have examined particular aspects of nature
      that should be associated with productive human habitats to see if they trigger
      positive responses in people. Tree form has emerged as an important factor in
      these studies. People prefer looking at trees with spreading forms much more than
      looking at trees with other forms. Trees with spreading forms existed on the
      African savanna and were associated with habitats that were good for early human
      habitation. We have shown that subjects also feel happier when looking at these
      trees than when looking at other trees or non-tree objects. Color is another
      variable that might be associated with people's responses to nature. Bright green
      colors could be an important cue for healthy plants with good nutrient qualities.
      We measured subjects' physiological responses to tree canopies of various colors
      and found that all colors were calming, but bright green trees were more calming
      than other tree colors, including less bright greens and oranges. Adult responses
      to plants are also influenced by their childhood interactions with nature. We
      have shown that the more interaction people have with nature as children, the
      more positive are their attitudes towards nature as adults. These positive
      responses have been documented in people from a wide range of backgrounds.

PMID- 17435349
TI  - Photoreception for circadian, neuroendocrine, and neurobehavioral regulation.
AB  - In the art and science of lighting, four traditional objectives have been to
      provide light that: 1) is optimum for visual performance; 2) is visually
      comfortable; 3) permits aesthetic appreciation of the space; and 4) conserves
      energy. Over the past 25 years, it has been demonstrated that there are
      nonvisual, systemic effects of light in healthy humans. Furthermore, light has
      been used to successfully treat patients with selected affective and sleep
      disorders as well as healthy individuals who have circadian disruption due to
      shift work, transcontinental jet travel, or space flight. Recently, there has
      been an upheaval in the understanding of photoreceptive input to the circadian
      system of humans and other mammals. Analytical action spectra in rodents,
      primates, and humans have identified 446-484 nm (predominantly the blue part of
      the spectrum) as the most potent wavelength region for neuroendocrine, circadian,
      and neurobehavioral responses. Those studies suggested that a novel photosensory
      system, distinct from the visual rods and cones, is primarily responsible for
      this regulation. Studies have now shown that this new photosensory system is
      based on a small population of widely dispersed retinal ganglion cells that are
      intrinsically responsive to light, and project to the suprachiasmatic nuclei and
      other nonvisual centers in the brain. These light-sensitive retinal ganglion
      cells contain melanopsin, a vitamin A photopigment that mediates the cellular
      phototransduction cascade. Although light detection for circadian and
      neuroendocrine phototransduction seems to be mediated principally by a novel
      photosensory system in the eye, the classic rod and cone photoreceptors appear to
      play a role as well. These findings are important in understanding how humans
      adapt to lighting conditions in modern society and will provide the basis for
      major changes in future architectural lighting strategies.

PMID- 17435350
TI  - Effects of monochromatic light on time sense for short intervals.
AB  - We examined the effects of monochromatic light on the time sense and the central
      nervous system. Nine young adult volunteers participated in this study. They were
      exposed to red-light and blue-light environments (illuminance was kept at 310
      lx). We evaluated the time sense by time-production tests of 90 s and 180 s and
      measured the P300 event-related potentials during an auditory oddball task. The
      90-s time intervals produced by subjects in the two monochromatic light
      conditions were not significantly different. However, the 180-s time interval
      produced in the red-light condition (163.2+/-50.4 s) was significantly (p<0.05)
      shorter than that in the blue-light condition (199.0+/-54.4 s). The peak latency
      of P300 in the red light (322.2+/-26.6 ms) was found to be significantly (p<0.05)
      shorter also than that in the blue light (332.6+/-20.2 ms). The feelings measured
      by the visual analogue scales in the two light conditions were not significantly
      different. These results indicate that the time sense ran faster in the red-light
      than in the blue-light condition. We suggest that the higher activity in the
      central nervous system that is accounted for by the shorter latency of P300 is
      related to the acceleration of the time sense.

PMID- 17435351
TI  - Age and gender differences in the physical activity patterns of urban
      schoolchildren in Korea and China.
AB  - Physical activity in childhood is important as it may establish adult behavior.
      However, few studies on physical activity in children have been conducted,
      especially in Asian children. We performed anthropometric measurements of 159
      school children in two grades (grade 5: 10-11 years old and grade 8: 13-14 years
      old) from urban areas of Korea (n=79) and China (n=80). The total daily energy
      expenditure (TEE) was estimated for 7 consecutive days using an accelerometer.
      The mean height, weight, and body mass index (BMI) for boys and girls in both
      countries exceeded the US national reference median (CDC, 2000). Physical
      activity levels (PALs) were significantly higher in the grade 5 group (10-11
      years old) and in girls than in boys for both grades. No significant difference
      in PALs or daily step-counts (STPs) was observed between 'normal' and
      'overweight' subgroups based on BMI, although negative correlations were found
      between weight, BMI, or %body fat vs. PAL or STP among Korean girls and Chinese
      boys (r=0.32-0.38, all p<0.05). Daily variation in physical activity was observed
      in Korean children. In the Koreans (boys and girls, both grades pooled), TEE and
      STP were significantly lower than the 7-day average on Sundays, whereas for the
      Chinese population, STP did not clearly differ between the weekends and the week
      averages. In summary, PALs were higher in the fifth grade boys and girls than in
      the eighth grade children; interestingly, girls tended to have higher PALs than
      boys. Daily variation in physical activity was observed in Korea; children were
      less active on Sundays.

PMID- 17435352
TI  - Human variation and body mass index: a review of the universality of BMI cut
      offs, gender and urban-rural differences, and secular changes.
AB  - Use of BMI as a surrogate for body fat percentage is debatable and universal BMI
      cut-off points do not seem appropriate; lower cut-off points than currently
      recommended by WHO should be used in some populations, especially in Asia. The
      adult WHO BMI database indicates that, on average, women are more obese than men,
      while men are more likely to be pre-obese than women. Urban rates of overweight
      and obesity are generally higher than rural rates in both sexes. The trend in pre
      obesity and obesity over time is generally upward, with very marked increases in
      the USA and UK in both sexes over the last 10 years.

PMID- 17435353
TI  - Variations in the light-induced suppression of nocturnal melatonin with special
      reference to variations in the pupillary light reflex in humans.
AB  - The purpose of the present study was to elucidate the existence of individual
      differences of pupil response to light stimulation, and to confirm the
      reproducibility of this phenomenon. Furthermore, the relationship between the
      individual differences in nocturnal melatonin suppression induced by lighting and
      the individual differences of pupillary light response (PLR) was examined. The
      pupil diameter and salivary melatonin content of 20 male students were measured
      at the same period of time (00:00-02:30 hr) on different days, accordingly.
      Illumination (530 nm) produced by a monochromatic light-emitting diode (LED) was
      employed as the light stimulation: pupil diameter was measured with 4 different
      levels of illuminance of 1, 3, 30 and 600 lux and melatonin levels were measured
      at 30 and 600 lux (respective controls were taken at 0 lux). Oral temperature,
      blood pressure and subjective index of sleepiness were taken in experiments where
      melatonin levels were measured. Changes of the pupil diameter in response to
      light were expressed as PLR and light-induced melatonin suppression was expressed
      as a control-adjusted melatonin suppression score (control-adjusted MSS), which
      was compared to the melatonin level measured at 0 lux. In the PLR, the
      coefficients of variation obtained at 30 lux or less were large (51.5, 45.0, 28.4
      and 6.2% at 1, 3, 30 and 600 lux, respectively). Correlations of illuminance of
      any combination at 30 lux or less were statistically significant at less than 1%
      level (1 vs. 3 lux: r=0.68; 1 vs. 30 lux: r=0.64; 3 vs. 30 lux: r=0.73), which
      showed the reproducibility of individual differences. The control-adjusted MSS at
      600 lux (-1.14+/-1.16) was significantly (p<0.05) lower than that registered at
      30 lux (-0.22+/-2.12). PLR values measured at 30 and 600 lux were then correlated
      with control-adjusted MSS; neither indicated a significant linear relationship.
      However, the control-adjusted MSS showed around 0 under any of the illuminance
      conditions in subjects with high PLR. In control-adjusted MSS of low values
      (i.e., melatonin secretions were easily suppressed), subjects indicated typically
      low PLR. In subjects with low control-adjusted MSS (n=3), characteristic changes
      in the autonomic nervous system, such as body temperature and blood pressure,
      were noted in subjects exposed to low illuminance of 30 lux. The fact that the
      relationship between PLR and control-adjusted MSS portray a similar pattern even
      under different luminance conditions suggests that MSS may not be affected in
      those with high PLR at low illuminance, regardless of the illuminance condition.

PMID- 17435354
TI  - Physiological effects of Shinrin-yoku (taking in the atmosphere of the forest)-
      using salivary cortisol and cerebral activity as indicators.
AB  - The purpose of this study is to examine the physiological effects of Shinrin-yoku
      (taking in the atmosphere of the forest). The subjects were 12 male students
      (22.8+/-1.4 yr). On the first day of the experiments, one group of 6 subjects was
      sent to a forest area, and the other group of 6 subjects was sent to a city area.
      On the second day, each group was sent to the opposite area for a cross check. In
      the forenoon, the subjects were asked to walk around their given area for 20
      minutes. In the afternoon, they were asked to sit on chairs and watch the
      landscapes of their given area for 20 minutes. Cerebral activity in the
      prefrontal area and salivary cortisol were measured as physiological indices in
      the morning at the place of accommodation, before and after walking in the forest
      or city areas during the forenoon, and before and after watching the landscapes
      in the afternoon in the forest and city areas, and in the evening at the place of
      accommodation. The results indicated that cerebral activity in the prefrontal
      area of the forest area group was significantly lower than that of the group in
      the city area after walking; the concentration of salivary cortisol in the forest
      area group was significantly lower than that of the group in the city area before
      and after watching each landscape. The results of the physiological measurements
      show that Shinrin-yoku can effectively relax both people's body and spirit.

PMID- 17435355
TI  - Characterization of distribution pattern of eye fixation pauses in observation of
      knotty wood panel images.
AB  - Wood is widely accepted as a human-friendly material. Many people use a large
      amount of wood in their living space. However, information on why and how humans
      are affected by wood is insubstantial. Understanding what a person is focusing on
      when looking at wood is an important first step in solving the above problem. The
      manner and style of our wood observation can be extracted directly by using an
      eye-tracker. The purpose of this study is to characterize the distribution
      pattern of eye fixation pauses in observing wood including many knots. Fifty-five
      kinds of wood panel images were prepared as visual stimuli. Various sizes of
      knots appeared on most of them. Twenty subjects observed these images for about
      20 seconds per image freely with the eye-tracker on their heads. Their eye
      movements were recorded as eyemarks during the observations, and many eye
      fixation pauses on each image were extracted for each subject. To express the
      distribution pattern of the eye fixation pauses quantitatively, two numerical
      indexes, the aspect ratio and the rate of expansion, were proposed in this study.
      The former index indicated the overall shape of the distribution, and the latter
      corresponded to the size of the observation area. Based on the relationships
      between these indexes, the distribution patterns were classified into three
      types.

PMID- 17435356
TI  - Physiological effects of Shinrin-yoku (taking in the atmosphere of the forest) in
      an old-growth broadleaf forest in Yamagata Prefecture, Japan.
AB  - The physiological effects of "Shinrin-yoku" (taking in the atmosphere of the
      forest) were examined by investigating blood pressure, pulse rate, heart rate
      variability (HRV), salivary cortisol concentration, and immunoglobulin A
      concentration in saliva. Subjective feelings of being "comfortable", "calm", and
      "refreshed" were also assessed by questionnaire. The subjects were 12 male
      university students aged from 21 to 23 (mean+/-SD: 22.0+/-1.0). The physiological
      measurements were conducted six times, i.e., in the morning and evening before
      meals at the place of accommodation, before and after the subjects walked a
      predetermined course in the forest and city areas for 15 minutes, and before and
      after they sat still on a chair watching the scenery in the respective areas for
      15 minutes. The findings were as follows. In the forest area compared to the city
      area, 1) blood pressure and pulse rate were significantly lower, and 2) the power
      of the HF component of the HRV tended to be higher and LF/(LF+HF) tended to be
      lower. Also, 3) salivary cortisol concentration was significantly lower in the
      forest area. These physiological responses suggest that sympathetic nervous
      activity was suppressed and parasympathetic nervous activity was enhanced in the
      forest area, and that "Shinrin-yoku" reduced stress levels. In the subjective
      evaluation, 4) "comfortable", "calm", and "refreshed" feelings were significantly
      higher in the forest area. The present study has, by conducting physiological
      investigations with subjective evaluations as supporting evidence, demonstrated
      the relaxing and stress-relieving effects of "Shinrin-yoku".

PMID- 17435357
TI  - Evaluating tactile sensitivity adaptation by measuring the differential threshold
      of archers.
AB  - This study investigated the relationship between the force applied to a finger
      and the differential threshold of the force. Further, it presented an improvement
      function for tactile perception in archers by adapting to circumstances in which
      enhanced tactile perception and finger dexterity are required to practice archery
      on a daily basis. For this purpose, a tactile display using an air jet was
      developed. The air was aimed at the center of the fingertip of the index finger.
      The inner diameter of the nozzle was set to 3 mm. In this study, a psychophysical
      experiment was conducted to obtain the differential threshold from two subject
      groups-an archery athlete group and a control group. A total of six levels of
      standard stimuli ranging from 2.0 gf to 7.0 gf was obtained. As a result, the
      differential threshold of the archery group was significantly higher than that of
      the control group. The Weber ratio of the archery group remained around 0.13 and
      that of control group was 0.10. The experiment also revealed that the
      differential threshold for archers exhibited less fluctuation between the trials
      and between the days, which implied that the tactile perception of archery
      athletes may be more stable than that of non-experienced subjects. This may be a
      plasticity property of tactile perception.

PMID- 17435358
TI  - The relationship between IMPS-measured stress score and biomedical parameters
      regarding health status among public school workers.
AB  - The aim of this study was to examine the relationship between the stress score
      measured using the Inventory to Measure Psychosocial Stress (IMPS) and biomedical
      parameters regarding health status among apparently healthy subjects in order to
      evaluate the validity of the IMPS. Out of the 1,941 public school workers in
      Kyushu and Okinawa, Japan, who were admitted to a hospital for medical check-ups,
      1,499 workers responded to questionnaires which assessed the degree of stress
      response (i.e., stress score) measured using the IMPS, and the degree of stress
      tolerance capacity (i.e., stress intolerance score) measured using the Inventory
      to Measure Stress Tolerance Capacity (IMST). One thousand two-hundred and one
      workers (684 men and 517 women) were analyzed, excluding 298 subjects who were
      taking medication for hypertension, hyperuricemia, hyperlipidemia and diabetes,
      or had a value for glycosylated hemoglobin (HbA1c)>or=6.0 percent. An increase in
      the stress score was positively associated with an increase in both body fat
      percentage and glycosylated hemoglobin values among men, while it was positively
      associated with an increase in plasma triglyceride concentrations among women.
      The stress score significantly correlated with the value for glycosylated
      hemoglobin even after controlling for age, body mass index, alcohol consumption,
      smoking, and exercise among men. An increase in the stress intolerance score was
      positively associated with an increase in body fat percentage among men, while it
      was positively associated with an increase in body weight, body mass index, and
      body fat percentage among women. Our result that the stress score measured using
      the IMPS was associated with obesity and unfavorable glycemic changes is in
      congruency with the model that psychosocial stress has a detrimental effect on
      humans by inducing obesity and insulin resistance, suggesting that the IMPS is a
      valid means to evaluate psychosocial stress levels among an otherwise healthy
      population.

PMID- 17435359
TI  - Study on legibility of characters for the elderly--effects of character display
      modes on legibility.
AB  - It is more crucial than ever to consider the elderly when designing products. One
      of the important things to remember is the legibility of characters, since this
      influences the accessibility and usability of products. We studied the effects of
      character attributes on legibility using 70 subjects (60 aged 46-79 with no
      apparent ocular problems except presbyopia, and 10 aged 68-80 with cataracts).
      Thirty 10-key television remote control models were made. The characters on each
      were different, and were based on combinations of three attributes-height (5
      levels), thickness (3 levels), and display mode (2 levels; positive: black
      characters on a white background, negative: white characters on a black
      background). Participants subjectively evaluated the legibility of the characters
      for each 10-key sample under two ambient illuminance conditions: 500 lx and 50
      lx. They also performed paired comparisons on samples with the same height and
      thickness but different display modes. Subjective data were analyzed using a
      three-way factorial ANOVA for character height, thickness, and display mode.
      Legibility was significantly affected by all factors for those without cataracts
      under both illuminance conditions, and the interaction between thickness and
      display mode was significant. A two-way factorial ANOVA was performed for height
      and display mode for each thickness. Legibility was, in general, better for
      thinner characters in negative mode and was better in negative mode under dark
      illuminance for those with and without cataracts. This tendency was more
      pronounced in the elderly (over 65 years old). Paired comparisons showed that
      legibility was better in negative mode under both illuminance conditions,
      especially with medium and thin characters, for those with and without cataracts.
      Although there are few accounts of the effects of positive and negative modes in
      various existing guidelines, this finding would suggest that legibility can be
      enhanced by using the negative mode.

PMID- 17435360
TI  - Comparison of stress responses between mental tasks and white noise exposure.
AB  - The purpose of this study was to compare the cardiovascular responses to
      different types of mental stress. Ten healthy males performed a mental arithmetic
      task (MA) on one day and were exposed to white noise (WN, 80dB) on another day.
      Both the MA and the WN were composed of four 5-min consecutive periods with a 3
      min rest between them. On each day, the systolic and diastolic blood pressure
      (SBP and DBP), mean arterial pressure (MAP), cardiac output (CO), and total
      peripheral resistance (TPR) were measured continually during the entire
      experimental period. The changes from the baseline (Delta) in all periods were
      calculated for both mental stresses. As for the results, the DeltaMAP, DeltaCO,
      DeltaHR, and DeltaTPR in the MA did not significantly change during the task
      periods. However, in the WN, the DeltaMAP and DeltaTPR showed significant
      increases over the time of the consecutive periods. In addition, we discuss the
      response patterns for the two mental stresses. We examine three hemodynamic
      reactivity patterns: a cardiac pattern characterized by increased CO and
      decreased TPR, a mixed pattern characterized by a moderate increase in both CO
      and TPR, and a vascular pattern characterized by increased TPR and decreased CO.
      The results show that throughout all task/exposure periods, the response pattern
      remained the same for six subjects in each stress. Furthermore, of these six
      subjects, half showed the same response pattern in both the MA and the WN. In
      conclusion, compared to the MA task, consecutive WN exposure showed an
      accumulation of stress responses. A change in TPR contributed to a gradual
      increase in MAP in the WN. It is also possible that among the subjects there were
      different types of response to the MA and WN.

PMID- 17435361
TI  - Inter- and intra-individual variations of heart rate variability in Japanese
      males.
AB  - Spectral components of heart rate variability (HRV) were repeatedly measured (4-8
      measurements; mean: 6 measurements) in 75 healthy Japanese male subjects (age
      range: 20-61) under two postural conditions (standing and supine). Low-frequency
      (LF) and high-frequency (HF) components and mean heart rate (HR) were analyzed
      with special reference to individual variations, which were classified into two
      types: inter- (interV) and intra-individual variations (intraV). The percent
      contributions and coefficients of variations were calculated for both interV and
      intraV. Percent contributions of intraV (intraV%) of HR with standing and supine
      postures were 15.8 and 12.9%, respectively. The intraV% of HF and LF on standing
      were 31.5 and 26.5%, while those in the supine posture were 27.8 and 35.5%,
      respectively. The coefficients of interV (interCV) and intraV (intraCV) were also
      calculated. The interCVs of HR, HF, and LF on standing were 14.9, 41.4, and
      48.4%, while those in the supine posture registered 16.2, 42.9, and 44.2%,
      respectively. The intraCVs of HR, HF, and LF on standing were 5.0, 19.7, and
      21.2%, while those in the supine posture indicated 4.7, 20.1, and 23.0%,
      respectively. We also calculated the interV and intraV of logarithmic-transformed
      HRV indexes. The log-transformation remarkably diminished both variables: interCV
      and intraCV registered 14-16 and 6-7%, respectively. Although interV variations
      were considerably large, intraV variations of HRV were negligibly small. The HRV
      indexes decreased with age, although HR remained unchanged. The coefficients of
      determination (r2) were 14-34%. In the case of log-transformed HRV indexes, the
      coefficients of determination registered 9-15%, suggesting that 14-34% (raw) or 9
      15% (log) of the observed interV may be due to variations in age.

PMID- 17435362
TI  - Insulation and body temperature of prepubescent children wearing a thermal
      swimsuit during moderate-intensity water exercise.
AB  - This study investigated thermal swimsuits (TSS) effects on body temperature and
      thermal insulation of prepubescent children during moderate-intensity water
      exercise. Nine prepubescent children (11.0+/-0.7 yrs) were immersed in water (23
      degrees C) and pedalled on an underwater cycle-ergometer for 30 min with TSS or
      normal swimsuits (NSS). The rectal temperature (Tre) was maintained slightly
      higher with TSS than with NSS. The total insulation (Itotal) was significantly
      higher with TSS. The DeltaTre, Deltamean body temperature (Tb), and tissue
      insulation (Itissue) in the NSS condition were correlated with % body fat, which
      indicated that the insulation layer of subjects with low body fat was thinner
      than that of obese subjects, and tended to decrease body temperature. Wearing TSS
      increased Itotal, thereby reducing heat loss from subjects' skin to the water.
      Consequently, subjects with TSS were able to maintain higher body temperatures.
      In addition, TSS is especially advantageous for subjects with low body fat to
      compensate for the smaller Itissue.

PMID- 17435363
TI  - The effect of aging on the backward stepping reaction as estimated from the
      velocity of center of foot pressure and muscular strength.
AB  - By estimating the deflection velocity from the center of foot pressure (COP),
      this study aims to prove that the characteristics of the backward stepping
      reaction in the elderly are related to the strength of the antigravity muscles.
      The participants in this study were 10 elderly (average age 75.6+/-7.6 years) and
      13 young (average age 22.0+/-2.6 years) subjects. Using force plate analysis, we
      measured the shift in the deflection velocity (V-RMS) and the maximum deflection
      velocity (V-MAX) from the beginning of the COP movement to the onset of the
      stepping reaction. Furthermore, we measured the strength of the antigravity
      muscles using a hand-held dynamometer. We correlated the V-RMS, V-MAX, and the
      rate of change of the deflection velocity (MAX/RMS) with muscular strength. When
      compared with the young subjects, the elderly showed significantly lower values
      of V-RMS (p<0.05) and significantly higher values of MAX/RMS (p<0.01).
      Furthermore, when compared with the young subjects, the elderly showed
      significantly lower values of muscular strength for all muscles studied
      (p<0.001). We established a significant correlation between the V-RMS, MAX/RMS,
      and muscular strength by carrying out a regression analysis (V-RMS: gluteus
      maximus (r=0.50, p<0.05) and rectus abdominis (r=0.48, p<0.05); MAX/RMS: adductor
      magnus (r=-0.66, p<0.001) and flexor digitorum longus (r=-0.62, p<0.01)).
      Differences were observed in the V-RMS and MAX/RMS during the backward stepping
      reaction; it was proposed that these differences were related to the age and
      muscular strength of the subjects. Therefore, further investigations should be
      undertaken in order to understand the effects of aging on the stepping reaction.
      In other words, the change-in-support strategy, including the preparatory phase
      of the stepping reaction, and its relationship with muscular strength should be
      further investigated.

PMID- 17435364
TI  - The influence of taste stimuli and illumination on electrogastrogram
      measurements.
AB  - An electrogastrogram (EGG) is considered to be an index to the autonomic nervous
      system of the digestive organs. In the present study, we attempted to clarify
      whether or not an EGG can be used to evaluate the influence of illumination, and
      what kinds of effect taste stimuli and illumination have on the autonomic nervous
      system. In this study, we used the ratio of the normal wave component of the EGG
      (EGG-NR: 2-4.5 cpm power/1-10 cpm power) and the amplitude of a normal wave (EGG
      NI: integrated EGG of 2-4.5 cpm). Thirteen healthy males participated in 16
      experimental conditions (4 lighting conditionsx4 taste stimuli). The four
      lighting conditions were set by combinations of illuminance levels of 200 and
      1500 lx and color temperatures of 3000 and 7500 K. The four taste stimuli were
      sweet (glucose), salty (salt), sour (acetic acid), and bitter (quinine). The
      changes in EGG-NR and EGG-NI were compared for different taste conditions. The
      results showed that EGG-NI was not significantly affected by the different taste
      conditions. However, the main effect of taste on EGG-NR was significant: sweet
      and salty tastes were significantly higher than the bitter taste. EGG-NR and EGG
      NI in different lighting conditions were also compared. The main effect of
      different color temperatures was also significant, but the illuminance level did
      not affect EGG-NR. EGG-NR increased significantly at the lower color temperature.
      On the other hand, EGG-NI significantly increased at the lower illuminance. These
      results suggest that parasympathetic nervous activity has a predominant effect on
      gastric activity in different lighting environments. Therefore, EGG measurements
      may be useful indicators for illumination environment studies.

PMID- 17435365
TI  - Lower extremity muscle activity during different types and speeds of underwater
      movement.
AB  - To compare the activity of lower extremity muscles during land walking (LW),
      water walking (WW), and deep-water running (DWR), 9 healthy young subjects were
      tested at self-selected low, moderate, and high intensities for 8 sec with two
      repetitions. Surface EMG electrodes were placed on the tibialis anterior (TA),
      soleus (SOL), medial gastrocnemius (GAS), rectus femoris (RF), and biceps femoris
      (BF). During DWR, the SOL and GAS activities were lower than LW and WW. The BF
      activities were higher during DWR than LW and WW. It was considered that the
      lower activity of SOL and GAS depended on water depth, and higher activity of BF
      occurred by greater flexion of the knee joint or extension of the hip joint
      during exercise.

PMID- 17435366
TI  - Correlation between breakfast tryptophan content and morning-evening in Japanese
      infants and students aged 0-15 yrs.
AB  - Tryptophan can be metabolized via 5-hydroxytryptamine=serotonin to melatonin by a
      series of 4 enzymes in pineal body. Lack of serotonin in body fluid in the brain
      during daytime can lead to several psychiatric disorders, while shortage of
      plasma-melatonin at night can be related to sleep disorders. The Morning-Evening
      (M-E) questionnaire and the original questionnaire including questions on sleep
      habits, mental symptoms, and contents of meals were administered to 1055 infants
      aged 0-6 yrs, 751 students attending an elementary school, and 473 students
      attending junior high school in Kochi City (33 degrees N). The index of
      tryptophan taken at breakfast (Trp-Index) was calculated as tryptophan amount per
      one meal based on the tryptophan included in each 100 g of the foods and a
      standard amount of food per one meal. A significant positive-correlation between
      M-E scores and Trp-Index was not shown by relatively older students, aged 9-15
      yrs (Pearson's test, r=0.044-0.123, p=0.071-0.505), whereas a significant
      positive correlation was shown by infants and young elementary school students
      aged 0-8 yrs (r=0.180, 0.258, p<0.001). The more frequently the infants had
      difficulty falling asleep at bedtime and waking up in the morning, the less the
      Trp-Indices taken at breakfast were (Kruskall-Wallis-test, p=0.027 for difficulty
      falling asleep; p=0.008 for difficulty waking up). The more frequently infants
      became angry even by a little trigger, or depressed, the lower (more evening
      typed) the M-E scores were (Kruskal-Wallis test: p<or=0.001). Tryptophan ingested
      at breakfast is very important for children to keep a morning-type diurnal
      rhythm, high quality of sleep, and indirectly good mental health, presumably,
      through the metabolism of tryptophan to serotonin in daytime and further to
      melatonin at night.

PMID- 17435367
TI  - Seasonal variations of melatonin secretion in young females under natural and
      artificial light conditions in Fukuoka, Japan.
AB  - The purpose of this study was to examine the seasonal variations of melatonin
      secretion of subjects and of their surrounding light conditions. Eight Japanese
      female students (20.1+/-2.6 yrs, Mean+/-SD) living in Fukuoka, Japan,
      participated in the present study. Saliva samples were collected every 3 hours
      over the course of a day, and the light intensity during daily life was measured
      every 1 min for 5 days in the four seasons. Almost all subjects had different
      melatonin secretory profiles in autumn, with only two subjects showing similar
      rhythms in all four seasons. The peak values of melatonin secretion calculated by
      a spline interpolation were higher in autumn than those in other seasons
      (p<0.001, Fisher's PLSD) and its peak time in this season was significantly
      delayed compared with those in spring and summer (p<0.05, Fisher's PLSD). The
      amount of time during daytime exposure to light of >1,000 lux was at least thirty
      minutes in all the seasons, and there were no significant differences among them.
      The relationship between peak level of melatonin secretion and amount of time of
      daytime light exposure to >1,000 lux was significant only in the autumn. During
      this season, there was a significant positive correlation (r=0.83, p<0.05, n=6),
      except for two subjects, whose melatonin secretion remained low.

PMID- 17435368
TI  - Evaluating the relationships between the postural adaptation of patients with
      profound cerebral palsy and the configuration of the Seating Buggy's seating
      support surface.
AB  - We are currently investigating the physiological polymorphism of wheelchair users
      with profound cerebral palsy and the properties of the Seating Buggy (developed
      by S. Nishimura, 1998) to clarify important and general elements of wheelchairs
      for widespread use. Cerebral palsy is a diagnostic term used to describe a group
      of motor syndromes resulting from disorders in early brain development. Recently,
      it has been shown that the Seating Buggy produces functional head-neck alignments
      and active control of sitting balance for people with profound cerebral palsy.
      The Seating Buggy is a wheelchair for the profoundly disabled and features a wide
      adjustment range from heights of 120 cm to 175 cm. Its seating support surface is
      comprised of a sling-seat. To examine the relationships between the postural
      adaptation of patients with profound cerebral palsy and the configuration of the
      Seating Buggy's seating, we assessed the postural alignment of the Seating
      Buggy's user and then measured the configuration of its resulting seating support
      surface with a three dimensional scanning system. Twenty-one subjects were used
      for the purposes of this investigation in their everyday environment. Postural
      adaptation and wheelchair fitting in the Seating Buggy were assessed from the
      viewpoint of the Active Balanced Seating by a seating expert. The subjects fell
      into two categories, as follows: 11 for appropriate or nearly appropriate
      fitting, and 10 for ill-fitting. The depth of thoracic support and the forward
      distance of lumbar support for those who claimed that it was ill-fitting were
      significantly reduced compared with that of those who claimed that the Seating
      Buggy offered an appropriate or nearly appropriate fitting. It was suggested that
      the properly adjusted depth of thoracic support and distance of the lumbar
      support were related to the resulting satisfactory head-neck alignment and
      sitting balance of the patients with profound cerebral palsy.

PMID- 17435369
TI  - Inhibitory effects of fermented nutraceuticals on NO production and T cell
      proliferation in juvenile atopic dermatitis.
AB  - As the most common inflammatory skin disease in children, atopic dermatitis
      begins in infancy or early childhood, with about 90% of cases appearing under age
      of 5. The prevalence of atopic dermatitis has rapidly increased among children in
      recent years. Physiological and psychological abnormalities and social impact are
      also well known in children with atopic dermatitis and in their families. Atopic
      dermatitis not only seriously affects the quality of life of the children and
      their families but also is leading chronic disease in children with hard-to
      cure.Recently, we found that the fermented extract of several plants had
      considerable potential to treat juvenile atopic dermatitis. This extract
      therefore is now under investigation to find the underlying immunopathological
      mechanism by determining its inhibitory effects on nitric oxide (NO) release and
      T cell proliferation. The fermented extract dose dependently blocked NO
      production. In particular, the inhibitory effect of the extract was maximized up
      until 80-fold dilution of the original extract. This extract did not induce
      cytotoxic effects up to 80-fold dilution. Interestingly, doses between 320- and
      80-fold dilution significantly protected cell death mediated by LPS-induced NO
      production. The fermented extract also significantly suppressed CD3 induced T
      cell proliferation in a dose dependent manner.

PMID- 17435370
TI  - Effect of physical training on body composition in Moscow adolescents.
AB  - The influence of physical activity on body mass components has been studied using
      a sample of Moscow children. 195 girls and 259 boys of Russian ethnicity from 12
      to 17 years old were investigated cross-sectionally in 2005 in different Moscow
      schools. According to the level of physical activity they were divided into three
      groups: 1-those who did not take part in regular physical exercise (44 boys and
      50 girls); 2-those who took part in special sports programs in general education
      schools (82 boys and 82 girls); 3-students of special sports schools with a high
      sports ranking (133 boys and 63 girls). The program included anthropometric
      measurements, evaluation of sexual maturation indices, somatotypes, and
      "functional" traits (diastolic and systolic blood pressure, pulse rate, hand
      grip, etc). For the study of body composition, bioelectrical impedance analysis
      (BIA) was used. The estimates of body mass components were also calculated using
      the anthropometric measurements. For the fat component, the estimates obtained by
      BIA and the anthropometric methods were highly correlated: r=0.85-0.88. Age
      changes of BIA measurements and body components were analysed. With multiple
      regression analysis it was shown that BIA measurements are dependent on a great
      number of morphological and functional traits, with the most informative sets of
      traits being selected. The degree of physical activity has a strong effect on
      body components: the contents of fat-free mass (FFM) and total body water (TBW)
      significantly increase, and the fat mass (FM) in girls decreases.

PMID- 17435371
TI  - Environmental and behavioral conditions of bathing among elderly Japanese.
AB  - This study investigated the bathing conditions of elderly Japanese, and sought to
      find factors relating to regional differences in death rates from bathtub
      accidents. A questionnaire survey was carried out in 11 areas of Japan.
      Questionnaires including questions regarding the length of time since houses had
      been built, types of facilities, and subjects' indoor thermal sensations and
      behavior while bathing were distributed to detached houses in each area twice,
      once in summer and once in winter. Completed questionnaires were collected from
      approximately 160 elderly people over 65 years old. Information regarding thermal
      sensations of rooms in winter revealed that a prefabricated bath and insulating
      window glass eased the cold in the bathroom. Unexpectedly, more subjects in the
      southern region than in the northern region reported being cold or a little cold
      while bathing in winter. In the present study, thermal sensations and behaviors
      while bathing seemed to be more affected by facilities and the location of houses
      than by the sex and age of the subjects.

PMID- 17435372
TI  - Anthropometric correlates of C-reactive protein among indigenous Siberians.
AB  - C-reactive protein (CRP) is an inflammatory marker, which at low-level elevations
      is associated with increased cardiovascular risk. Although CRP has been
      extensively investigated in North American and European settings, few studies
      have measured CRP among non-Western groups. The present study used dried whole
      blood spot samples to examine high-sensitivity CRP concentrations among the Yakut
      (Sakha) of Siberia (85 females, 56 males; 18-58 years old). Our goals were: (1)
      to compare Yakut CRP concentrations with other populations; (2) to investigate
      sex differences; and (3) to explore anthropometric correlates of CRP. Results
      indicate that serum equivalent CRP concentrations are similar to those from
      industrializing nations, lower than US and European values, and greater than
      Japanese concentrations. Yakut men and women display similar CRP concentrations;
      however, CRP was significantly higher among men after adjustment for body fat,
      age, and smoking. Positive associations were documented between CRP and BMI, body
      fat, and central adiposity.

PMID- 17435373
TI  - Evaluation of the sedative effect of fragrance on Filipinas using a biochemical
      marker.
AB  - The purpose of this study is to evaluate the usefulness of salivary amylase
      activity as an indicator of the acute psychological sedative effects of
      fragrances used in household products such as clothing softeners. Twenty seven
      healthy Philippine female subjects in their late 30 s were enrolled (38.7+/-5.2
      yr). This study was undertaken to investigate the favorite fragrance of Asian and
      Pacific Islander women. Our results indicated that (i) a mixed floral fragrance
      might be a favorite fragrance for Filipinas; (ii) fragrances contained in a
      softener significantly induced a sedative effect in humans, as assessed by both
      analysis of the biochemical marker and subjective evaluation; (iii) salivary
      amylase activity has the potential to be an excellent indicator for the
      evaluation of the acute psychological sedative effects of fragrance.

PMID- 17435374
TI  - Precision of measurement as a component of human variation.
AB  - This paper describes the main quality control methods for determining human
      observer measurement error and instrument error focusing on intra-observer and
      inter-observer technical error of measurements (TEMs) and relative TEM, and the
      coefficient of reliability (R). R values above 0.95 are indicative of small
      errors. To compare variances between different variables, the coefficient of
      variation, a measure of relative variability, is used. The total variation of a
      character can be partitioned into genetic, environmental, and error components.
      Determination of the genetic component of variation (heritability) is usually
      obtained from twin studies or other family studies. A good environment improves
      the population mean, whereas a poor environment can lower the population mean
      without any change in the underlying genetic structure. Worked examples of how to
      calculate TEM, R, and heritability are provided.

PMID- 17435375
TI  - Heart rate and electroencephalogram changes caused by finger acupressure on
      planta pedis.
AB  - Preliminary experiments were carried out to investigate the feasibility of using
      an electroencephalogram and heart rates to evaluate the efficacy of finger
      acupressure on the key points of planta pedis (both soles). Continuous
      electroencephalograms were recorded from 19 electrodes based on the International
      10-20 electrode placement system on 22 university students (21+/-2.3 years).
      Spectral power changes were obtained at each electrode site. The power of the
      alpha1 frequency range (8-10 Hz) increased slightly during acupressure although
      no statistical significance was observed, while heart rates decreased in all
      subjects (p<0.05). Cerebral cortex asymmetry in the spectral power changes was
      not clearly observed during the right and left sole acupressure. This preliminary
      study suggests that a classification of subjects is necessary in understanding
      brain wave data during acupressure on soles.

PMID- 17435376
TI  - A new method for the simultaneous detection of mammalian cells and ion tracks on
      a surface of CR-39.
AB  - The geometric locations of ion traversals in mammalian cells constitute important
      information in the study of heavy ion-induced biological effects. We employed a
      contact microscopy technique, which was developed for boron imaging in boron
      neutron capture therapy to the irradiation mammalian cells by low-energy heavy
      ions. This method enables the simultaneous visualization of mammalian cells as a
      relief on a plastic track detector, CR-39, and the etch pits which indicate the
      positions of ion traversals. This technique provides visual geometric information
      about the cells and ion traversal, without any specially designed devices or
      microscopes. Only common laboratory equipment, such as a conventional optical
      microscope, a UV lamp, and commercially available CR-39 is required. To validate
      this method, CHO-K1 and HeLa cells were cultured on the CR-39 surface and then
      irradiated with low-energy Ar and Ne ions, respectively. The positions of induced
      DNA double strand breaks were detected as gamma-H2AX fluorescent spots, which
      coincided with the positions of the etch pits in the cell relief image.

PMID- 17435377
TI  - Enhancement of tumor radioresponse by wortmannin in C3H/HeJ hepatocarcinoma.
AB  - The objective of this study was to explore whether a specific inhibitor of PI3K,
      wortmannin, could potentiate the antitumor effect of radiation in vivo,
      particularly on radioresistant murine tumors. C3H/HeJ mice bearing syngeneic
      hepatocarcinoma (HCa-I) were treated with 25 Gy radiation, wortmannin, or both.
      Wortmannin was administered intraperitoneally (1 mg/kg) once daily for 14 days.
      Tumor response to treatment was determined by a tumor growth delay assay.
      Possible mechanisms of action were explored by examining the level of apoptosis
      and regulating molecules. The expression of regulating molecules was analyzed by
      Western blot for p53 and p21(WAF1/CIP1), and immunohistochemical staining for
      p21(WAF1/CIP1), CD31 and VEGF. In the tumor growth delay assay, wortmannin
      increased the effect of tumor radioresponse with an enhancement factor (EF) of
      2.00. The level of apoptosis achieved by the combined treatments was shown to be
      no more than an additive effect; peak apoptotic index was 11% in radiation alone,
      13% in wortmannin alone, and 19% in the combination group. Markedly increased
      areas of necrosis at 24 h in the combination group were noted. Western blotting
      showed upregulation of p21(WAF1/CIP1) in the combination treatment group, which
      correlated with low levels of VEGF. Microvascular density was evidently also
      reduced, based on low expression of CD31. In murine hepatocarcinoma, the
      antitumor effect of radiation was potentiated by wortmannin. The mechanism seems
      to involve not only the increase of induced apoptosis but also enhanced vascular
      injury. Wortmannin, in combination with radiation therapy, may have potential
      benefits in cancer treatment.

PMID- 17435378
TI  - Effects of Dai-kenchu-to on spontaneous activity in the mouse small intestine.
AB  - The effects of Dai-kenchu-to (DKT), a Chinese medicine, on spontaneous activity
      of mouse small intestine were investigated. Experiments were carried out with
      tension recording and intracellular recording. DKT contracted mouse longitudinal
      smooth muscles in a dose dependent manner (0.1-10 mg/ml). Low concentration of
      DKT (0.1 mg/ml) did not contract the longitudinal muscles of mouse small
      intestine. DKT (0.1 mg/ml) inhibited contraction elicited by transmural nerve
      stimulation (TNS). DKT (1 mg/ml) evoked relaxation before contraction. The
      initial relaxation was abolished by Nomega-nitro-L-arginine (L-NNA). DKT (10
      mg/ml)-induced contraction had two components: a transient rapid contraction and
      a following slow contraction. Atropine inhibited DKT (1 mg/ml)-induced
      contraction to about 50% of control. In the presence of atropine, tetrodotoxin
      (TTX) inhibited the contraction elicited by DKT (1 mg/ml) to about 80%. DKT
      depolarized the membrane and decreased the amplitude of pacemaker potentials
      recorded from in situ myenteric interstitial cells of Cajal (ICC-MY) with no
      alteration to the frequency, duration and maximum rates of rise in the presence
      of nifedipine and TTX. The same results were obtained in slow waves recorded from
      circular smooth muscle cells. These results indicate that DKT evoked both
      contraction and relaxation by releasing acetylcholine, nitric oxide and other
      excitatory neurotransmitters in mouse small intestine. DKT had no effects on
      pacemaker mechanisms and electrical coupling between ICC-MY and smooth muscle
      cells in mouse small intestine. The results also suggest that DKT may contract
      smooth muscles by depolarizing the membrane directly.

PMID- 17435379
TI  - Effects of 5-hydroxytryptamine on electrical responses of circular smooth muscle
      isolated from the guinea-pig gastric antrum.
AB  - The effects of 5-hydroxytryptamine (5-HT) on electrical responses of the membrane
      were investigated in circular smooth muscle isolated from the guinea-pig stomach
      antrum. Small segment of circular muscle tissue produced a periodical generation
      of slow potentials at frequency of 0.1-2 cycles min(-1), during random generation
      of unitary potentials. Application of 5-HT (10(-7)-10(-5) M) hyperpolarized the
      membrane and either increased or decreased the frequency of slow potentials, both
      with associated increase in amplitude of slow potential. These effects of 5-HT
      were abolished by methysergide. N(omega)-nitro-L-arginine (L-NA) increased the
      frequency of spontaneously generated slow potentials and also increased the
      frequency of slow potentials generated during stimulation with 5-HT, suggesting
      an involvement of the increased production of nitric oxide (NO) by 5-HT. Atropine
      did not alter spontaneous and 5-HT-induced electrical responses. The
      hyperpolarization produced by 5-HT was associated with a decrease in input
      resistance and time constant of the membrane. The amplitude of the 5-HT-induced
      hyperpolarization was increased in low [K(+)](o) solution and decreased in high
      [K(+)](o) solution or in the presence of glybenclamide, suggesting that the
      hyperpolarization was produced by activation of ATP-sensitive K-channels. The
      increase in amplitude of slow potentials by 5-HT may be secondary due to
      hyperpolarization of the membrane. The inhibition by 5-HT of the frequency of
      slow potentials may be partly due to the increased release of NO, however the
      mechanism by which dual effects of 5-HT on the frequency of slow potentials
      remains unsolved.

PMID- 17435380
TI  - Studies on the mechanisms underlying beta-adrenoceptor-mediated relaxation of rat
      abdominal aorta.
AB  - Mechanisms underlying beta-adrenoceptor (beta-AR)-mediated vascular relaxation
      were studied in the isolated rat abdominal aorta. In the endothelium-denuded
      helical preparations, a non-selective beta-AR agonist isoprenaline elicited a
      concentration-dependent relaxation. In the absence of beta-AR antagonists,
      isoprenaline-induced relaxation was not practically affected by an adenylyl
      cyclase inhibitor SQ 22,536 (300 microM), but was strongly diminished by high-KCl
      (80 mM). Isoprenaline-induced relaxation in the presence of SQ 22,536 was
      significantly diminished by iberiotoxin (IbTx, 0.1 microM), but was not affected
      by 4-aminopyridine (4-AP, 3 mM). Isoprenaline-induced relaxation was not also
      affected by SQ 22,536 (300 microM) even in the presence of CGP20712A (a beta(1)
      selective antagonist) and ICI-118,551 (a beta(2)-selective antagonist) (0.1
      microM for each), but was strongly diminished by high-KCl. By contrast, SQ 22,536
      resistant, isoprenaline-induced relaxation in the presence of CGP20712A plus ICI
      118,551 was not affected by IbTx (0.1 microM), but was inhibited significantly by
      4-AP (3 mM). These results suggest that in rat abdominal aortic smooth muscle: 1)
      both beta(1)-/beta(2)-AR- and beta(3)-AR-mediated relaxations substantially
      involve cAMP-independent mechanisms; 2) beta(1)-/beta(2)-AR-mediated, cAMP
      independent relaxant mechanisms are partly attributed to the large-conductance,
      Ca (2+)-sensitive K(+) (MaxiK, BK) channel whereas beta(3)-AR-mediated relaxant
      mechanisms are attributed to K(v) channel.

PMID- 17435381
TI  - Response of alveolar type II epithelial cells to mechanical stretch and
      lipopolysaccharide.
AB  - BACKGROUND: Although many therapeutic strategies have been developed clinically,
      the mortality associated with acute respiratory distress syndrome remains very
      high. OBJECTIVES: In this research, we used a cytomechanical method to elucidate
      the reason for this. METHODS: A549 cells were stimulated with lipopolysaccharide
      (LPS; 1 or 100 ng/ml) and/or mechanical stretch (5, 15, 30%) in varying frequency
      (0.2, 0.5, 1 Hz) at indicated time (1, 2, 4 h). Real time PCR and enzyme-linked
      immunosorbent assay were used to measure mRNA and protein levels of IL-8.
      RESULTS: In the presence of mechanical stretch, 100 ng/ml LPS significantly
      increased IL-8 production after 4 h of 5% stretch (p < 0.05). In the presence of
      LPS, stretch enhanced LPS-induced IL-8 protein production in a force-, time- and
      frequency-dependent manner. At both the 1- and 4-hour time points, mechanical
      stretch and LPS increased IL-8 mRNA levels, respectively, and stretch enhanced
      LPS-induced IL-8 mRNA levels (p < 0.05). CONCLUSIONS: Using cytomechanic methods,
      we found a synergistic effect of LPS and mechanical stretch on IL-8 production.
      The response of alveolar type II cells to mechanical stretch depends on their
      different pathologic states and the applied mechanical stretch, which may
      reversely influence the outcome of patients with acute respiratory distress
      syndrome.

PMID- 17435382
TI  - Long-term benefits of inhaled tobramycin in children with cystic fibrosis: first
      clinical observations from Poland.
AB  - BACKGROUND: Respiratory disease is the major cause of mortality in cystic
      fibrosis (CF) patients and inhaled antibiotic therapy may contribute to the
      stabilization of lung function. OBJECTIVES: This is a small, open, uncontrolled,
      observational study of clinical experience obtained with 2 years of maintenance
      treatment with inhaled tobramycin in 12 children and adolescents with CF.
      METHODS: Twelve subjects aged 6-18 years infected by Pseudomonas aeruginosa were
      qualified for treatment with inhaled tobramycin. Pulmonary function, weight and
      height, clinical status, and chest X-ray were continually monitored. After an
      active 2-year treatment period, results of all measured parameters in our
      patients were compared with their previous results (2-year period before
      treatment with tobramycin). RESULTS: During 2 years before treatment with
      tobramycin solution for inhalation (TOBI), pulmonary function decline was
      observed, the median value of FEV(1) change was -7.6% (lower quartile -13.1,
      upper quartile -5.9). After 2 years of treatment, FEV(1) percent predicted value
      declined by 1.5% (lower quartile -11.1, upper quartile 3.7) from baseline; 2
      years of TOBI therapy significantly reduced lung function decline (p = 0.049).
      There were no significant changes in thoracic gas volume and specific airway
      resistance before and after treatment. Two years of TOBI therapy significantly
      improved body mass index (p = 0.02). TOBI treatment significantly delayed
      progression of pulmonary X-ray changes assessed by Brasfield score (p = 0.02).
      CONCLUSIONS: We found that patients with CF can gain substantial benefits from
      long-term TOBI treatment, including reduced pulmonary function decline, delayed
      progression of pulmonary X-ray changes and improved weight gain in growing
      children and adolescents.

PMID- 17435384
TI  - Diffusion-weighted imaging following transcranial Doppler shunt studies.

PMID- 17435383
TI  - Quantitative carotid calcium scoring and cerebral ischemia - a pilot study and
      review of recent literature.

PMID- 17435385
TI  - Carotid endarterectomy in a patient with persistent proatlantal artery.

PMID- 17435386
TI  - Clinicoradiological characteristics of cerebral air embolism.

PMID- 17435387
TI  - Danaparoid in the prevention of ischemic stroke in paroxysmal nocturnal
      hemoglobinuria.

PMID- 17435388
TI  - The main components of stroke unit care: what is the question?

PMID- 17435390
TI  - Assessing and using comorbidity measures in elderly veterans with lower extremity
      amputations.
AB  - BACKGROUND: Understanding comorbidity prevalence and the effects of comorbidities
      in older veterans with lower extremity amputations may aid in assessing patient
      outcomes, resource use, and facility-level quality of care. OBJECTIVES: To
      determine the degree to which adding outpatient to inpatient administrative data
      sources yields higher comorbidity prevalence estimates and improved explanatory
      power of models predicting 1-year mortality and to compare the Charlson/Deyo and
      Elixhauser comorbidity measures. METHODS: A retrospective cohort study applying
      frequencies, cross-tabulations, and logistic regression models was conducted,
      including data from 2,375 veterans with lower extremity amputations. Comorbidity
      prevalence according to the Charlson/Deyo and Elixhauser measures, 1-year
      mortality rates, and standardized mortality ratios (SMRs) were analyzed. RESULTS:
      Comorbidity prevalence estimates increased sharply for both the Charlson/Deyo and
      Elixhauser measures with the addition of data from multiple settings. The
      Elixhauser compared to the Charlson/Deyo generally yielded higher estimates but
      did not improve explanatory power for mortality. Modeling expected versus actual
      deaths produced varying SMRs across geographic regions but was not dependent on
      which measure or data sources were used. CONCLUSIONS: Merging outpatient with
      inpatient data may reduce the under coding of comorbidities but does not enhance
      mortality prediction. Compared to the Charlson/Deyo, the Elixhauser has a more
      complete coding scheme for comorbid conditions, such as diabetes mellitus and
      peripheral vascular disease, important to addressing lower extremity amputation
      etiology.

PMID- 17435391
TI  - Up-regulation in expression of vesicular glutamate transporter 3 in substantia
      nigra but not in striatum of 6-hydroxydopamine-lesioned rats.
AB  - Overactivity of the glutamatergic system is suggested to be closely related to
      the onset and pathogenesis of Parkinson's disease. Vesicular glutamate
      transporters (VGLUT1, T2 and T3) are a group of glutamate transporters in neurons
      that are responsible for transporting glutamate into synaptic vesicles and they
      are key elements for homeostasis of glutamate neurotransmission. The present
      study was aimed to investigate the expression of VGLUT1, T2 and T3 proteins after
      the onset of Parkinson's disease. A rat model of Parkinson's disease, the 6
      hydroxydopamine-lesioned rat, was employed. Immunocytochemistry revealed that
      VGLUT1, T2 and T3 immunoreactivity was not modulated in the striatum of the
      lesioned rat. Western blotting analyses also showed that there was no change in
      the expression of T1, T2 and T3 proteins in the striatum. In contrast, no VGLUT1
      protein was detected in the substantia nigra. After the lesion, levels of VGLUT2
      immunoreactivity and protein were not modulated. Significant increase of VGLUT3
      immunoreactivity was observed in the perikarya of GABAergic substantia nigra pars
      reticulata neurons (+14.7%) although VGLUT3 protein was not modulated in the
      nigral tissues. VGLUT3 in GABAergic neurons is suggested to play a role in GABA
      synthesis. The present results may therefore implicate that VGLUT1 and T2 are not
      modulated in the striatum and the substantia nigra of the 6-hydroxydopamine
      lesioned rat and only VGLUT3 plays a role in pathogenesis of Parkinson's disease.

PMID- 17435392
TI  - Effects of anesthetics on the function of orexin-1 receptors expressed in Xenopus
      oocytes.
AB  - Neurons in the hypothalamus containing the neuropeptide orexin have been
      implicated in the control of sleep and wakefulness and in the pathology of
      narcolepsy. In this study, we investigated the effects of volatile anesthetics,
      ethanol and intravenous anesthetics on orexin-A-induced Ca2+-activated Cl-
      currents using Xenopus oocytes expressing orexin-1 receptors (OX1Rs). The
      volatile anesthetics isoflurane, enflurane and halothane inhibited Cl- currents
      elicited by 1-micromol/l orexin-A. Ethanol and the intravenous anesthetics
      pentobarbital and ketamine also inhibited the action of orexin-A. The inhibitory
      effects of all of the compounds tested were shown to be caused by the inhibition
      of OX1R function. These results may, at least in part, explain their hypnotic
      effects.

PMID- 17435393
TI  - Phonetic typology and positional allophones for alveolar rhotics in Catalan.
AB  - The present study reports electropalatographic and acoustic data on the
      positional and contextual characteristics of alveolar taps and trills in
      Majorcan, Valencian and Eastern Catalan. The two consonant classes are invariably
      opposed by degree of tongue dorsum contact and F2, but only differentiated by
      place of articulation when constriction location for the trill is sufficiently
      retracted. Trills are produced with less than three contacts and may exhibit a
      single contact in utterance-initial position and, less often, in /Cr, VrV/
      sequences. Word-final and, to a lesser extent, preconsonantal rhotics are
      implemented as taps in Majorcan and Valencian, and strengthened into trills in
      Eastern Catalan. Moreover, there appears to be an inverse relationship between
      initial strengthening, and intervocalic weakening and the absence of syllable
      final strengthening, for Valencian rhotics, which could be indicative of a
      pattern of intersegmental organization. Shortening and articulatory reduction
      turned out not to be necessarily related for extremely short Valencian taps,
      which undergo much undershoot intervocalically but are highly constricted in /C ,
      rC/ sequences. Other research aspects such as devoicing and intergestural timing
      for Catalan alveolar rhotics are also investigated.

PMID- 17435394
TI  - Analysis of tones in Cantonese speech based on the command-response model.
AB  - As one of the major Chinese dialects, Cantonese has a tone system consisting of
      nine lexical tones and three additional changed tones, which is considerably more
      complex than that of Mandarin. The most important acoustic feature characterizing
      these tones is the contour of the voice fundamental frequency (the F(0) contour).
      In this article we present an approach to modeling F(0) contours of Cantonese
      utterances, based on an extension of the command-response model. Analysis
      bysynthesis of F(0) contours of the utterances with a fixed carrier frame, in
      which a target syllable with each tone type is embedded, shows that each tone
      type can be represented by a specific pattern (polarity, timing, and amplitude)
      of tone commands. These patterns are found to be essentially maintained in F(0)
      contours of the utterances with unconstrained text. With the definition of these
      tone command patterns, the command-response model not only provides a novel
      phonological description of tones, but also gives high accuracy of approximations
      to F(0) contours of Cantonese utterances and allows one to analyze various tonal
      phenomena in quantitative terms. Quantitative distinctions between various tones
      are then revealed by statistical analysis of the timing and amplitude of tone
      commands. Especially, systematic alignment in timing is found between the
      onsets/offsets of tone commands and the rhyme of a syllable, and hence a set of
      constraints can be introduced, which together with those on tone command
      amplitudes and phrase command parameters, is then applied for generating F(0)
      contours of Cantonese utterances. The validity of the approach is verified by
      perceptual evaluation of the synthetic speech stimuli with model-generated F(0)
      contours, both on the intelligibility of tones and on the naturalness of prosody.

PMID- 17435399
TI  - Effects of a postpartum back pain relief program for Korean women.
AB  - PURPOSE: Despite the high prevalence of back pain and its subsequent effects in
      post-partum women, intervention programs are scarce. The purpose of this study
      was to test the effects of a back-pain-reducing program on post-partum women who
      experienced low-back pain during pregnancy. METHODS: A non-equivalent control
      group pretest-posttest design was used. Pregnant women who attended a hospital
      for prenatal check-ups and experienced back pain participated in an intervention
      program (n=27), and the results were compared with women in a control group from
      another hospital (n=25). RESULTS: At 8 weeks post-partum, the pain intensity,
      functional limitations were lower in the intervention group than in the control
      group. However, differences in mean change of the pain intensity and functional
      limitations between 36 and 39 weeks of gestation and at 8 weeks post-partum were
      not statistically significant between the groups. Moreover, the flexibility, post
      partum functional status, and post-partum depression did not differ significantly
      between the groups. CONCLUSIONS: A back-pain-relief program in this study was not
      effective to reduce the back-pain intensity in post-partum women and to decrease
      the associated functional limitations. The implications for nursing practice and
      directions for future research are discussed.

PMID- 17435400
TI  - Trends in patient satisfaction from 1989-2003: adjusted for patient
      characteristics.
AB  - PURPOSE: To identify trends in patient satisfaction adjusted for sociodemographic
      factors and health status from 1989-2003. METHODS: Five repeated cross-sectional
      surveys were used. The study sample included 290,534 household members 20 years
      of age and over from the five survey periods of 1989, 1992, 1995, 1999, and 2003.
      Satisfaction was measured using a five-point scale, ranging from "very satisfied"
      to "very dissatisfied." Crude satisfaction rates, representing the proportion of
      patients satisfied (very satisfied or satisfied), were calculated for each survey
      period. Satisfaction rates adjusted for age, sex, marital status, education, and
      self-rated health status were calculated for each of the five years. RESULTS:
      Crude satisfaction rates increased from 15.4% in 1989 to 40.5% in 2003. The
      proportions of satisfaction and dissatisfaction were reversed after 15 years had
      passed. However, the satisfaction trend was not linear throughout the different
      years, with 1992 being the year with the lowest satisfaction rate (9.7%). These
      trends in crude rates did not change even after adjusting for patient
      characteristics. The odds of satisfaction in 1992 were 38% lower (odds ratio
      0.62, 95% CI 0.60 to 0.64) than the odds in 1989. In 2003, the odds of
      satisfaction were 4.01 times (95% CI 3.89 to 4.13) the odds for 1989. Older,
      female, married, and less-educated people were more likely to be satisfied.
      Patients who rated their health as "very good" had the highest satisfaction rate,
      and those with "neutral" health ratings had the lowest. General hospitals
      achieved substantial improvement whereas pharmacies became the lowest-rated of
      all institutions. CONCLUSIONS: The Korean health system has achieved better
      patient satisfaction rates over the past 15 years. Increased health expenditure,
      resources, and quality improvement efforts may have contributed to this progress.

PMID- 17435401
TI  - A study on knowledge and attitudes regarding sexuality of elderly people in
      Korea.
AB  - PURPOSE: The purpose of this study was to examine the level of knowledge and the
      attitudes of Korean adults toward sexuality of elderly people. METHODS: This was
      a descriptive study using a convenience sample of 241 adults. The questionnaire
      had 34 items for knowledge and 26 items for attitudes. RESULTS: The result showed
      that, related to sexuality of elderly people, the level of knowledge was average
      and attitudes were conservative. The level of knowledge was significantly higher
      in groups that were highly educated and of low economic status (p<.05). Attitudes
      toward sexuality of elderly people were significantly more conservative in
      female, older, less educated, and high economic status group. CONCLUSION: The
      findings suggest a need for more education for Korean adults regarding sexuality
      in elderly people.

PMID- 17435402
TI  - The effectiveness of the error reporting promoting program on the nursing error
      incidence rate in Korean operating rooms.
AB  - PURPOSE: The purpose of this study was to develop and evaluate an error reporting
      promoting program(ERPP) to systematically reduce the incidence rate of nursing
      errors in operating room. METHODS: A non-equivalent control group non
      synchronized design was used. Twenty-six operating room nurses who were in one
      university hospital in Busan participated in this study. They were stratified
      into four groups according to their operating room experience and were allocated
      to the experimental and control groups using a matching method. Mann-Whitney U
      Test was used to analyze the differences pre and post incidence rates of nursing
      errors between the two groups. RESULTS: The incidence rate of nursing errors
      decreased significantly in the experimental group compared to the pre-test score
      from 28.4% to 15.7%. The incidence rate by domains, it decreased significantly in
      the 3 domains-"compliance of aseptic technique", "management of document",
      "environmental management" in the experimental group while it decreased in the
      control group which was applied ordinary error-reporting method. CONCLUSION:
      Error-reporting system can make possible to hold the errors in common and to
      learn from them. ERPP was effective to reduce the errors of recognition-related
      nursing activities. For the wake of more effective error-prevention, we will be
      better to apply effort of risk management along the whole health care system with
      this program.

PMID- 17435403
TI  - Transformational experience of a student nurse with diabetes: a case study.
AB  - PURPOSE: The current study was aimed to investigate the transformational
      experience of a female student nurse living with type 1 diabetes. METHODS: A case
      study of a 24-year-old diabetes patient was conducted, with interviews concerning
      the evolving process she had lived through during the period from her later high
      school years to her graduation from nursing college. RESULTS: Followings were
      identified as 5-transformation process: With her diabetes-related limitation, the
      participant experienced 'conflict involving choosing a college and major'. The
      participant tried to be in charge of managing her diabetes and stepped forward to
      'adaptation to college life as a new environment', and she learned more about the
      process of 'evolving awareness of caring' and developed herself further through
      the process of 'integration of the nurse identity into self-identity', and
      finally through the process of 'progression and preparation for getting a job'
      she achieved her goals, being positive about the future. CONCLUSIONS: The results
      of the study can provide individuals with diabetes a way of self-management and
      help the patients and their families in diabetes education. Further research will
      be needed to refine the results of this study and to learn more about the
      experiences of patients with type I diabetes in college years.

PMID- 17435404
TI  - Needs for home care nursing in the vulnerable elderly.
AB  - PURPOSE: The purpose of this study was to determine the subjects' health status
      according to the needs of visiting health and the function of the family in home
      care nursing. SAMPLE AND METHOD: The data collection period was from 07/01/04 to
      10/31/04 and the subjects were 488 of those above 60 years of age staying at home
      or living alone who registered at a visiting health service of public health
      center at an urban area in Korea. This survey was carried out by visiting health
      nurses and participation was agreed on by the elderly people. RESULTS: The extent
      of the subjects' total health status to the general characteristics had
      differences according to the age, sex, monthly income, perceived health status,
      known functional disorder, and yes-or-no for disease. At all health status
      domains, visiting health need care in the group I was very lower than one in II,
      III, or IV groups. Also the severe dysfunctional family was lower than lightly
      dysfunctional family and normal functional family in all health status domains.
      CONCLUSION: Nurses must provide their characteristics considered nursing
      intervention for the elderly who have high visiting health needs and severe
      dysfunctional family with vulnerable health care.

PMID- 17435405
TI  - Nursing philosophy: Foucault and cultural diversity issues in the nursing field.
AB  - Cultural diversity is a highly important issue in nursing education and nursing
      practice today. This study is a philosophical approach to the power relationship
      between a health care provider and a care recipient. The main purpose of this
      paper is to analyze the relationships between nurses and ethnic minority patients
      based on the discussions of some Foucauldian concepts that are related to
      cultural diversity. Based on the analysis, this study provides some suggestions
      for cultural competency in nursing practice.

PMID- 17435406
TI  - The influence of culture on the experiences of Korean, Korean American, and
      Caucasian-American family caregivers of frail older adults: a literature review.
AB  - PURPOSE: The purpose of this review is to explore cultural influences on the
      experiences of Korean, Korean American, and Caucasian American family caregivers
      caring for frail older adults in terms of the selection of a primary caregiver,
      caregiving motivation, support/help-seeking, and negative emotional
      responses(depression and burden). METHODS: Seven electronic databases were
      searched to retrieve studies from 1966 to 2005. Thirty-two studies were
      identified. RESULTS: This review supported cultural influences on the selection
      of primary caregiver, caregiving motivation, and support/help-seeking among the
      three caregiver groups. In Korean caregivers, the major primary caregivers were
      daughters-in-law while among Korean American and Caucasian American caregivers,
      the major primary caregivers were daughters or spouses. As a major caregiving
      motivation, Caucasian American caregivers reported filial affection while Korean
      caregivers and Korean American caregivers reported filial obligation. Korean
      caregivers reported higher extended family support, while Caucasian American
      caregivers reported higher utilization of formal support. Korean caregivers
      showed the highest levels of depression followed by Korean American caregivers
      and Caucasian American caregivers. CONCLUSION: In order to develop culturally
      appropriate interventions and policies, more research is needed to further
      explain these differences among the three groups, especially regarding
      support/help-seeking and negative emotional responses.

PMID- 17435407
TI  - Effects of skin rehabilitation massage therapy on pruritus, skin status, and
      depression in burn survivors.
AB  - PURPOSE: Hypertrophic scarring and depression are the principal problems of burn
      rehabilitation. This study was done to verify the effects of skin rehabilitation
      massage therapy (SRMT) on pruritus, skin status, and depression for Korean burn
      survivors. METHODS: A pretest-posttest design using a nonequivalent control group
      was applied to examine the effects of SRMT for 3 months in a group of 18 burn
      survivors. The major dependent variables-including pruritus, objective and
      subjective scar status, and depression-were measured at the beginning and at the
      end of the therapy to examine the effects of SRMT. RESULTS: Burn survivors
      receiving SRMT showed reduced pruritus, improved skin status, and depression. The
      remaining scar also showed improvement in skin pigmentation, pliability,
      vascularity, and height (compared to the surrounding skin) as measured on the
      Vancouver Scar Scale (VSS). CONCLUSIONS: The findings demonstrate that SRMT for
      burn survivors may improve their scars both objectively and subjectively, and
      also reduce pruritus and depression.

PMID- 17435408
TI  - Associations between smoking and depression in adolescence: an integrative
      review.
AB  - BACKGROUND: Although research has established the existence of an association
      between smoking and depression among adolescents, researchers have not reached
      consensus on the nature of the association. OBJECTIVES: The purpose of this paper
      is to review the literature, to examine the nature of the relationship between
      smoking and depression in adolescence, and to suggest future research directions.
      METHOD: A literature search was conducted from the following six databases: (a)
      Ovid MEDLINE, (b) CINAHL, (c) PubMed Unrestricted, (d) PsycINFO, (e) ERIC, and
      (f) Sociological Abstracts. The combinations of the words, "depression,"
      "smoking," "tobacco," "adolescent," and "teen" were used for keyword searches to
      find relevant articles. RESULTS: In 47 of 57 studies, significant associations
      between smoking and depression were found. However, these significant
      relationships may either be spurious or unrelated to depression because a
      substantial number of studies did not adjust for confounders or did not use
      validated instruments to measure depression. Additionally, if the relationship is
      causal, its direction remains controversial. Five relationships have been
      suggested: (a) Depression causes smoking, (b) smoking causes depression, (c)
      there is a bidirectional relationship between smoking and depression, (d) smoking
      and depression occur due to confounders, and (e) subgroups with different
      relationships between the two conditions exist. CONCLUSIONS: It is necessary to
      further explore the relationship between smoking and depression. Future research
      should consider the need for: (a) longitudinal research designs, (b) more
      accurate measurement of depression, and (c) the control of confounders between
      smoking and depression.

PMID- 17435409
TI  - Subjective and objective caregiver burden in Parkinson's disease.
AB  - PURPOSE: Parkinson's disease (PD) is a common neurodegenerative disorder
      characterized by motor disabilities and increasing dependence on others for daily
      life activities with consequent impact on patients' and caregivers' quality of
      life. The aim of this study was to elucidate the burden on primary caregivers of
      patients with PD, and identify related factors. METHODS: A cross-sectional
      descriptive study. Seventy-six primary caregivers of PD patients in a neurology
      outpatient clinic, Seoul, Korea completed structured questionnaires, of which 68
      were analyzed. The structured self-report questionnaire included (1) demographic
      information on the caregivers, (2) information regarding the disease
      characteristics of the patients, and (3) the subjective and objective caregiver
      burdens as assessed on Montgomery, Gonyea, & Hooyman's scale. RESULTS: The mean
      age of the caregivers was 54.56 years, and spouses represented the largest
      proportion(47.0%). Caregivers of PD patients experienced high levels of burden
      (mean scores on the subjective and objective burdens were 45.22 and 34.90,
      respectively), which were comparable to the caregiver burdens in stroke, and
      higher than the caregiver burdens in general chronic disease. Older caregivers
      and spousal caregivers experienced significantly higher burdens (p=.004 and
      p=.019, respectively). A greater motor disability and higher modified Hoehn and
      Yahr grade were related to higher caregiver burden (p=.001 and p=.018,
      respectively). CONCLUSION: Caring for PD patients is associated with a high level
      of caregiver burden. Therefore, healthcare professionals should identify the
      burden of caregivers who look after PD patients and develop comprehensive
      management strategies both for patients and their caregivers.

PMID- 17435410
TI  - Effects of a Sun-style Tai Chi exercise on arthritic symptoms, motivation and the
      performance of health behaviors in women with osteoarthritis.
AB  - PURPOSE: Tai Chi exercise, an ancient Chinese martial art, has drawn more and
      more attention for its health benefits. The purpose of the study was to identify
      the effects of a Sun-style Tai Chi exercise on arthritic symptoms (joint pain and
      stiffness), motivation for performing health behaviors, and the performance of
      health behaviors among older women with osteoarthritis. METHODS: Total of 72
      women with the mean age of 63 years old were recruited from outpatients clinic or
      public health centers according to the inclusion criteria and assigned randomly
      to either the Tai Chi exercise group or the control. A Sun-style Tai Chi exercise
      has been provided three times a week for the first two weeks, and then once a
      week for another 10 weeks. In 12 weeks of study period, 22 subjects in the Tai
      Chi exercise group and 21 subjects in the control group completed the posttest
      measure with the dropout rate of 41%. Outcome variables included arthritic
      symptoms measured by K-WOMAC, motivation for health behavior, and health
      behaviors. RESULTS: At the completion of the 12 week Tai Chi exercise, the Tai
      Chi group perceived significantly less joint pain (t=-2.19, p=0.03) and stiffness
      (t=-2.24, p=0.03), perceived more health benefits (t=2.67, p=0.01), and performed
      better health behaviors (t=2.35, p=0.02), specifically for diet behavior (t=2.06,
      p=0.04) and stress management (t=2.97, p=0.005). CONCLUSION: A Sun-style Tai Chi
      exercise was found as beneficial for women with osteoarthritis to reduce their
      perceived arthritic symptoms, improve their perception of health benefits to
      perform better health behaviors.

PMID- 17435411
TI  - Vitamin D deficiency and secondary hyperparathyroidism among patients with
      chronic kidney disease.
AB  - BACKGROUND: Chronic kidney disease (CKD) is associated with morbid complications
      that lead to high mortality and costs. Vitamin D deficiency and secondary
      hyperparathyroidism (SHPT) are frequent complications of CKD. METHODS: We
      reviewed the current literature regarding the prevalence, diagnosis,
      complications, and management of vitamin D deficiency and SHPT among patients
      with CKD. RESULTS: There is a high prevalence of vitamin D deficiency among
      adolescents and adults in the United States (age and gender dependent). Patients
      with CKD or those who are dialysis-dependent are much more likely to have low
      levels of vitamin D in comparison to those without kidney disease. In order to
      avoid significant complications including SHPT and musculoskelatal diseases,
      vitamin D needs to be measured routinely by primary care physicians and
      nephrologists. In the majority of CKD patients, SHPT is not diagnosed until late,
      leading to advanced cardiovascular and bone diseases. CONCLUSIONS: In conclusion,
      current management of vitamin D deficiency and SHPT is suboptimal. Early
      diagnosis of vitamin D deficiency and SHPT are integral to optimal management of
      CKD, and additional research is needed in this area.

PMID- 17435412
TI  - Interrelationship between insulin resistance and menopause on the metabolic
      syndrome and its individual component among nondiabetic women in the kinmen
      study.
AB  - BACKGROUND: The literature to date is not clear as to whether any interactive
      effect exists between insulin resistance and menopause on the metabolic syndrome
      and its individual components. We explored this issue in 4107 homogeneous,
      nondiabetic Chinese women in the Kinmen Study. METHODS: Overnight fasting blood
      samples were drawn for glucose, insulin, lipid, and other biochemical
      measurements. Demographic and clinical variables including body mass index, waist
      circumference, and blood pressure were measured and documented during face-to
      face interviews with structured questionnaires. Menstrual history was used to
      define menopause as the absence of menses for 12 consecutive months. RESULTS:
      Approximately 16% of premenopausal women (390/2423) were insulin-resistant. After
      adjustment for age, body mass index, lifestyle, and diet, both menopause and
      insulin resistance were independently and significantly correlated with metabolic
      syndrome. For each component of the metabolic syndrome, besides the main effect,
      the interaction (insulin resistance x menopause) had significant correlation with
      systolic blood pressure, diastolic blood pressure, and waist circumference.
      CONCLUSIONS: Both insulin resistance and menopause have significant effects on
      metabolic syndrome independent of age and obesity. In premenopausal and
      nondiabetic women, various degrees of insulin resistance exist. The synergistic
      contribution of insulin resistance and menopause to components of the metabolic
      syndrome were observed with systolic blood pressure, diastolic blood pressure,
      and waist circumference. This requires further study.

PMID- 17435413
TI  - Influenza parotitis: a case from the 2004 to 2005 vaccine shortage.
AB  - We report a case of acute parotitis due to influenza A in which, unlike other
      published cases, the diagnosis was confirmed by demonstration of subtyped
      influenza A, serological evidence of mumps immunity, and full recovery without
      antibiotic treatment. In the United States, acute infectious parotitis was
      historically caused primarily by symptomatic paramyxovirus (mumps) infections,
      but because of the near-universal administration of the measles, mumps and
      rubella vaccine, other infectious and noninfectious etiologies now predominate.
      We discuss the differential diagnosis and therapeutic and public health
      considerations of parotitis and influenza. Due to time-sensitive pharmacologic
      management and possibly far-reaching public health issues, providers should be
      aware of atypical influenza presentations, such as parotitis.

PMID- 17435414
TI  - A large abdominal wall mass as an initial manifestation of malignant
      mesothelioma.
AB  - Malignant mesothelioma is relatively rare and usually presents with pleural
      thickening and effusion at onset. In this report, we describe a 67-year-old male
      patient whose initial manifestation of mesothelioma was a large mass in the left
      flank. Mesothelioma was diagnosed from needle biopsy specimens, and, after
      radiotherapy, the tumor did not recur in this area. However, pleural effusion
      developed, which was controlled by pleurodesis, and tumors appeared around the
      descending aorta. Despite further radiotherapy, the patient died of cardiac
      tamponade due to tumor invasion 38 months after the initial diagnosis. To the
      best of our knowledge, this is the first description of malignant mesothelioma
      presenting via initial invasion of the abdominal wall without changes in the
      thoracic space.

PMID- 17435415
TI  - Remarkable effect of gefitinib retreatment in a patient with nonsmall cell lung
      cancer who had a complete response to initial gefitinib.
AB  - Gefitinib is an orally active epidermal growth factor receptor tyrosine kinase
      inhibitor, and it shows favorable antitumor activity against chemorefractory
      nonsmall cell lung cancer (NSCLC). However, patients with NSCLC have few
      treatment options available if they are refractory to gefitinib. We describe a 49
      year-old patient with NSCLC who had a complete response to initial gefitinib that
      lasted for 12 months. The tumor relapsed, and the patient received cytotoxic
      chemotherapy. However, despite chemotherapy, the patient had radiographic
      progression of lung metastases and we commenced retreatment with gefitinib,
      showing a remarkable effect. Epidermal growth factor receptor (EGFR) gene
      analysis showed deletion mutations in codon 745-750 in exon 19 and EGFR gene
      amplification. Our case shows that after retreatment with gefitinib, patients may
      show a remarkable response if they showed a remarkable response to initial
      gefitinib administration and if a certain time has elapsed since the previous
      gefitinib treatment.

PMID- 17435416
TI  - Reversible congestive heart failure related to profound hypocalcemia secondary to
      hypoparathyroidism.
AB  - A 71-year-old man presented with acute pulmonary edema related to new onset of
      severe left ventricular dysfunction (ejection fraction, 30%). His symptoms did
      not improve with emergency therapy with diuretics and dobutamine. He was noted to
      be severely hypocalcemic (5.5 mg/dL) and subsequently showed dramatic improvement
      in symptoms and ejection fraction (58%) with correction of hypocalcemia with
      intravenous calcium and calcitriol replacement. Hypocalcemia was related to
      surgically induced hypoparathyroidism. The patient had been instructed to
      decrease calcium supplements and to discontinue calcitriol 3 months previously
      due to hypercalcemia. Additional factors that may have contributed to
      hypocalcemia included vitamin D deficiency, alendronate therapy for osteoporosis,
      and chronic kidney disease. We concluded that the patient's congestive heart
      failure was precipitated by severe hypocalcemia and resolved with correction of
      hypocalcemia. Hypocalcemia is a rare cause of reversible congestive heart failure
      that should be in the differential diagnosis in any patient presenting with heart
      failure and not responding to traditional therapy.

PMID- 17435417
TI  - Outdoor air pollution: overview and historical perspective.
AB  - Outdoor air pollution is a significant public health hazard in population centers
      throughout the world. Recognition of air pollution as a nuisance dates back many
      centuries. Decades of research have established a strong link between air
      pollution and a spectrum of adverse health effects. Health care practitioners
      rarely consider the health risk of air pollution in the course of patient care
      and generally do not provide risk modification strategies as part of patient
      management. The purpose of this article is to provide front line clinicians with:
      1) an overview of the evolution in scientific understanding about air pollution
      and its health effects, 2) an introduction to the hazards contemporary air
      pollution presents to patients, and 3) an introduction to the contributions of
      specific pollutants to outdoor air quality.

PMID- 17435418
TI  - Outdoor air pollution: particulate matter health effects.
AB  - Numerous investigations studying multiple populations across a variety of
      environmental settings have demonstrated a strong association between ambient air
      particulate matter and cardiopulmonary morbidity and mortality. In most studies,
      the effect size of ambient air particulate pollution on health outcomes is small.
      However, the exposed population worldwide is very large. Accordingly, particulate
      air pollution appears to be an important public health hazard that makes an
      important contribution to the total burden of disease and death in populations
      across the world. Much of the evidence linking ambient air particulates with
      adverse health effects is derived from population-based, observational research
      with potential unidentified confounding exposures, precluding definitive
      assessments about causation and providing limited mechanistic insights. A growing
      body of research suggests particulate-associated adverse health effects result
      from the induction of proinflammatory responses in the lower respiratory tract.
      Ambient air particulates may increase lung cancer risk.

PMID- 17435419
TI  - Outdoor air pollution: ozone health effects.
AB  - Ozone is a respiratory irritant associated with a spectrum of adverse health
      events. Ground-level ozone has been shown to cause decreases in lung function and
      has been associated with other important respiratory health effects. Some reports
      suggest short-term increases in ozone lead to increased cardiopulmonary
      mortality. Other studies have found no association between exposure and measured
      health effects. Outdoor air pollution consists of multiple copollutant exposures
      complicating definitive assessments about ambient air ozone exposure-effect
      relations.

PMID- 17435420
TI  - Outdoor air pollution: nitrogen dioxide, sulfur dioxide, and carbon monoxide
      health effects.
AB  - Nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide are important
      ambient air pollutants. High-intensity, confined space exposure to NO2 has caused
      catastrophic injury to humans, including death. Ambient NO2 exposure may increase
      the risk of respiratory tract infections through the pollutant's interaction with
      the immune system. Sulfur dioxide (SO2) contributes to respiratory symptoms in
      both healthy patients and those with underlying pulmonary disease. Controlled
      human exposure studies have demonstrated that experimental SO2 exposure causes
      changes in airway physiology, including increased airways resistance. Both acute
      and chronic exposure to carbon monoxide are associated with increased risk for
      adverse cardiopulmonary events, including death. However, studies have not
      demonstrated a clear dose-dependent health risk response to increasing amounts of
      these pollutants except at high concentrations. In addition, a number of studies
      examining the effects of ambient level exposure to NO2, SO2, and CO have failed
      to find associations with adverse health outcomes.

PMID- 17435421
TI  - Outdoor air pollution: counseling and exposure risk reduction.
AB  - Air pollution is monitored on a daily basis in large population centers in the
      United States and reported to the general public through a variety of media
      outlets as the Air Quality Index. This index is based on current national air
      quality standards for criteria air pollutants established by the US Environmental
      Protection Agency. Patients at increased risk for adverse effects of inhaled air
      pollutants include those who have been diagnosed with chronic lung disease and
      cardiovascular disease, including asthma, chronic obstructive pulmonary disease,
      coronary artery disease, congestive heart failure, and peripheral vascular
      disease, although others may also be at risk during periods of unusually high
      pollutant levels. These patients should be educated regarding what symptoms may
      be related to poor air quality and how they can monitor the Air Quality Index to
      modify their activity to prevent symptoms and other adverse events. Heavy outdoor
      exertion should be avoided on days expected to have poor air quality, or
      performed earlier in the day on days when outdoor activity cannot be avoided. We
      recommend advising patients in clear, strong, personalized language that air
      pollution is harmful and that persons with cardiopulmonary disease are at
      elevated risk of experiencing a serious adverse health effect from exposure.

PMID- 17435424
TI  - 25-Gauge transconjunctival sutureless vitrectomy.
AB  - PURPOSE OF REVIEW: The history and development of 25-gauge transconjunctival
      sutureless vitrectomy are reviewed in this paper. The expanded spectrum of
      appropriate cases and recent innovations in vitrectomy surgery are discussed, as
      are longer-term outcomes and possible complications. RECENT FINDINGS: 25-Gauge
      pars plana vitrectomy has evolved significantly since its introduction in 2002,
      with newer instruments and novel techniques expanding the scope and improving
      outcomes in vitreoretinal surgery. Proper case selection is imperative, as the
      smaller scale of the instruments and decreased fluidics work most efficiently
      when extensive manipulation of intraocular tissue or significant membrane
      dissection is not required. Unique complications of 25-gauge surgery such as
      hypotony and a possible increased rate of endophthalmitis may be related to
      unsutured sclerotomies, and revisions in surgical approach may help to decrease
      these potentially devastating complications. SUMMARY: Clinical experience over
      the last several years has proven that this sutureless system is both safe and
      efficacious. Decreased surgical times, reduced postoperative inflammation, and
      more rapid patient recovery have all contributed to an increased acceptance of 25
      gauge vitrectomy by retinal physicians.

PMID- 17435423
TI  - Vital dyes for chromovitrectomy.
AB  - PURPOSE OF REVIEW: The aim of this article is to present the current state-of-the
      art in regard to the application of vital dyes during vitreoretinal surgery,
      'chromovitrectomy', as well as to overview the current literature regarding the
      properties of dyes, techniques of application, indications, and complications in
      chromovitrectomy. RECENT FINDINGS: A large body of published research has
      recently addressed the toxicity profile of indocyanine green for
      chromovitrectomy. Experimental data demonstrate dose-dependent toxicity of
      indocyanine green to various retinal cells. Newer generation vital dyes for
      chromovitrectomy include trypan blue, patent blue, triamcinolone acetonide,
      infracyanine green, sodium fluorescein, bromophenol blue, fluorometholone acetate
      and brilliant blue. Novel instruments may enable a selective painting of
      preretinal tissues during chromovitrectomy. SUMMARY: This review suggests that
      the field of chromovitrectomy represents an expanding area of research. The first
      line agents for internal limiting membrane staining in chromovitrectomy are
      indocyanine green, infracyanine green, and brilliant blue. Patent blue,
      bromophenol blue and trypan blue arose as outstanding biostains for visualization
      of epiretinal membranes. Novel dyes available for chromovitrectomy deserve
      further investigation.

PMID- 17435425
TI  - Value-based medicine and interventions for macular degeneration.
AB  - PURPOSE OF REVIEW: The aim of this article is to review the patient value
      conferred by interventions for neovascular macular degeneration. RECENT FINDINGS:
      Value-based medicine is the practice of medicine based upon the patient value
      (improvement in quality of life and length of life) conferred by an intervention.
      For ophthalmologic interventions, in which length-of-life is generally
      unaffected, the value gain is equivalent to the improvement in quality of life.
      Photodynamic therapy delivers a value gain (improvement in quality of life) of
      8.1% for the average person with classic subfoveal choroidal neovascularization,
      while laser photocoagulation for the same entity confers a 4.4% improvement in
      quality of life. Preliminary data suggest the value gain for the treatment of
      occult/minimally classic choroidal neovascularization with ranibizumab is greater
      than 15%. The average value gain for statins for the treatment of hyperlipidemia
      is 3.9%, while that for the use of biphosphonates for the treatment of
      osteoporosis is 1.1% and that for drugs to treat benign prostatic hyperplasia is
      1-2%. SUMMARY: Interventions, especially ranibizumab therapy, for neovascular
      macular degeneration appear to deliver an extraordinary degree of value compared
      with many other interventions across healthcare.

PMID- 17435426
TI  - Age-related macular degeneration: the costs to society and the patient.
AB  - PURPOSE OF REVIEW: The current literature was reviewed to assess the patient and
      societal costs associated with age-related macular degeneration (ARMD). RECENT
      FINDINGS: An increasing number of studies discuss the growing direct
      ophthalmologic, direct nonophthalmologic, and indirect costs associated with
      ARMD. Most reports, however, focus on only one of these aspects. The prevalence
      of this debilitating disease will increase as life expectancy increases. SUMMARY:
      ARMD continues to be a major public health problem in developed countries. The
      treatment and management of exudative ARMD are changing dramatically. These
      therapies will likely become a more significant portion of the overall healthcare
      burden of ARMD. To date, no comprehensive study exists that attempts to calculate
      the total cost of ARMD.

PMID- 17435427
TI  - Pharmacoeconomics and macular degeneration.
AB  - PURPOSE OF REVIEW: To describe pharmacoeconomics and its relationship to drug
      interventions. RECENT FINDINGS: Pharmacoeconomics is the branch of economics
      which applies cost-minimization, cost-benefit, cost-effectiveness and cost
      utility analyses to compare the economics of different pharmaceutical products or
      to compare drug therapy to other treatments. Among the four instruments, cost
      utility analysis is the most sophisticated, relevant and clinically applicable as
      it measures the value conferred by drugs for the monies expended. Value-based
      medicine incorporates cost-utility principles but with strict standardization of
      all input and output parameters to allow the comparability of analyses, unlike
      the current situation in the healthcare literature. SUMMARY: Pharmacoeconomics is
      assuming an increasingly important role with regard to whether drugs are listed
      on the drug formulary of a country or province. It has been estimated that the
      application of standardized, value-based medicine drug analyses can save over 35%
      from a public healthcare insurer drug formulary while maintaining or improving
      patient care.

PMID- 17435428
TI  - Nonsteroidal drugs for the treatment of noninfectious posterior and intermediate
      uveitis.
AB  - PURPOSE OF REVIEW: This review summarizes current nonsteroidal drug therapies for
      noninfectious posterior and intermediate uveitis. RECENT FINDINGS: Continuing
      evidence shows that second-line agents including antimetabolites, T-cell
      inhibitors and alkylating agents, are effective in many patients, allowing
      reduction in steroid dose and preservation of visual function. There is an
      increased use of mycophenolate mofetil. Biologic therapies, including the
      antitumour necrosis factor-alpha agents and interferons, have demonstrated a high
      degree of efficacy in controlling uveitis refractory to immunosuppressants.
      SUMMARY: There are an increasing number of treatment options. As the vast
      majority of published studies in uveitis are case series or nonrandomized trials,
      there remains a lack of level 1 evidence to guide the choice and duration of
      therapy. Standard initial treatment for steroid-resistant disease is to add a
      single immunosuppressant to the regime, with additional agents being substituted
      or added as required. Combination of two immunosuppressants in addition to
      steroids may be indicated especially in chronic uveitis. High cost and limited
      long-term experience with biologic agents have restricted their use to uveitis
      refractory to immunosuppressants, but evidence suggests a potential therapeutic
      role earlier in Bechet's disease.

PMID- 17435430
TI  - Time course of posterior vitreous detachment in the second eye.
AB  - PURPOSE OF REVIEW: Posterior vitreous detachment is the principal predisposing
      event for the development of retinal breaks and rhegmatogenous retinal
      detachments. Patients with unilateral posterior vitreous detachment are
      potentially at risk of developing the complications associated with posterior
      vitreous detachment in the fellow eye. Thus, to identify when posterior vitreous
      detachment develops in the fellow eye after it develops in the first eye is
      important for managing patients with unilateral posterior vitreous detachment.
      RECENT FINDINGS: The main theme in the literature is research regarding the
      mechanism of the development of posterior vitreous detachment. Various
      pharmacologic vitreolysis agents can induce posterior vitreous detachment.
      Changes in the enzymatic activities in the vitreous and vitreoretinal interface
      tend to promote vitreous separation from the inner retinal surface with aging.
      Clinical studies have shown a significant increase in the occurrence of posterior
      vitreous detachment with aging, and the interval between the development of
      posterior vitreous detachment in the first eye and in the second eye is short.
      SUMMARY: Posterior vitreous detachment is one of the most important age-related
      changes in human eyes, and age-related changes develop equally in both normal
      eyes; thus, posterior vitreous detachment may develop in the second eye within a
      few years of developing in the first eye.

PMID- 17435429
TI  - Nutritional supplementation in age-related macular degeneration.
AB  - PURPOSE OF REVIEW: This review assesses the current status of the knowledge of
      the role of nutrition in age-related macular degeneration - a leading cause of
      vision loss in the persons with European ancestry. RECENT FINDINGS: We will
      evaluate the different nutritional factors and both observational and
      interventional studies used to assess the association of nutrition with age
      related macular degeneration. Persons with intermediate risk of age-related
      macular degeneration or advanced age-related macular degeneration in one eye are
      recommended to take the formulation proven in the Age-Related Eye Disease Study
      (AREDS) to be successful in preventing the development of advanced age-related
      macular degeneration by 25%. The formulation consists of vitamins C, E, beta
      carotene and zinc. In addition, observational data suggest that high dietary
      intake of macular xanthophylls lutein and zeaxanthin are associated with a lower
      risk of advanced age-related macular degeneration. Similarly, long-chain
      polyunsaturated fatty acids derived from fish consumption are also associated
      with a decreased risk of advanced age-related macular degeneration. SUMMARY:
      Persons with intermediate age-related macular degeneration or advanced age
      related macular degeneration (neovascular or central geographic atrophy) in one
      eye should consider taking the AREDS-type supplements. Further evaluation of
      nutritional factors, specifically, lutein/zeaxanthin and omega-3 fatty acids will
      be tested in a multicenter controlled, randomized trial - the Age-Related Eye
      Disease Study 2 (AREDS2).

PMID- 17435431
TI  - Current understanding and management of retinopathy of prematurity.
AB  - PURPOSE OF REVIEW: Retinopathy of prematurity is the leading cause of childhood
      blindness in industrialized countries and is the fifth leading cause of bilateral
      childhood blindness worldwide. There have been new insights into understanding
      the factors involved in the pathogenesis of retinopathy of prematurity and
      related retinal detachment. This review outlines the current recommendations for
      initiation, frequency, and duration of screening examinations and describes the
      infants at the highest risk for developing complications from retinopathy of
      prematurity. The rationale and timing of treatment are also discussed. RECENT
      FINDINGS: Infants who undergo early screening and treatment for retinopathy of
      prematurity have improved long-term functional and structural outcomes compared
      with those who receive conventional screening and treatment. Patients undergoing
      surgical repair of retinopathy of prematurity-related detachments (stage 4A, 4B
      and 5) can have favorable anatomical and functional outcomes. The increased
      survival of lower birth weight infants has increased the prevalence of
      aggressive, posterior retinopathy of prematurity that may be unresponsive to
      conventional treatment. SUMMARY: While full understanding of the mechanisms that
      underlie the formation of retinopathy of prematurity and related detachments is
      not complete, progress has been made in identifying risk factors, screening of
      high-risk patients, and optimizing the timing of surgical interventions to
      improve structural and functional outcomes.

PMID- 17435432
TI  - Drug delivery methods for posterior segment disease.
AB  - PURPOSE OF REVIEW: New pharmacotherapies for posterior segment diseases of the
      eye have been recently introduced which use novel drug delivery methods. The
      various current and potential future methods will be discussed. RECENT FINDINGS:
      Drug delivery systems have been developed which can provide controlled release of
      drug for potentially long periods of time. Ideal candidates for these devices are
      chronic conditions that require repeated local administration of drug, such as
      noninfectious intermediate or posterior uveitis, neovascular age-related macular
      degeneration, and persistent macular edema due to diabetic retinopathy or venous
      occlusive disease. Recently, Retisert (Bausch & Lomb, Rochester, New York, USA),
      a nonbiodegradable fluocinolone acetonide implant, was approved for use in
      noninfectious uveitis affecting the posterior segment and is currently in
      clinical trials for the treatment of macular edema. A biodegradable dexamethasone
      implant is currently in clinical trials for the treatment of uveitis and diabetic
      macular edema. SUMMARY: With the development of therapeutic agents that require
      repeated administration comes a need for new strategies to improve safety and
      maximize efficacy. Novel drug delivery systems involving nonbiodegradable or
      biodegradable implants, microparticulates or nanoparticulates, liposomes, or
      transscleral iontophoresis may provide the solution.

PMID- 17435433
TI  - Treatment of neovascular age-related macular degeneration: past, present and
      future directions.
AB  - PURPOSE OF REVIEW: The treatment options of choroidal neovascularization due to
      age-related macular degeneration have expanded. Prior to ocular photodynamic
      therapy the only available treatment was laser photocoagulation. Clinicians and
      patients were not particularly enthusiastic despite its ability to stabilize
      vision. The purpose of the review is to review the past and current concepts of
      neovascular age-related macular degeneration therapy and to provide a short
      overview of upcoming treatments. RECENT FINDINGS: Photodynamic therapy provided
      us with the first realistic means to address subfoveal choroidal
      neovascularization lesions from age-related macular degeneration. Antivascular
      endothelial growth factors now allow better visual outcomes than mere
      stabilization of vision and other promising treatments are undergoing study at
      this time. SUMMARY: Age-related macular degeneration therapy has undergone a
      significant revolution in recent years. Understanding the historical perspective
      of treatment provides a better appreciation of current therapies. Still there is
      no cure for this disease and more promising treatments are currently under
      investigation.

PMID- 17435434
TI  - Bibliography. Current world literature. Retinal, vitreous and macular disorders.

PMID- 17435436
TI  - Studying vulnerable populations: lessons from the Roma minority.
AB  - There are important disparities in health outcomes between racial/ethnic
      minorities and majorities in all countries where minority health has been
      investigated. This holds true for the largest minority population of Europe, the
      Roma, although research data related to Roma are scarcer and more contested than
      for other minorities. We discuss major obstacles that hinder or prevent the
      collection of reliable data in Roma and other minorities. The definitions and
      classification systems on race/ethnicity vary widely, pointing to the social
      construction of both race and ethnicity. Imprecision in taxonomy and definition
      of target groups is compounded by challenges in data collection, analysis, and
      interpretation, along with ethnocentricity that shapes the perspectives and
      approaches of the researchers. However, administrative data collection on
      race/ethnicity serves legitimate purposes although such data must comply with
      less-stringent quality requirements as opposed to data meant for scientific
      analysis. Research on minorities should consider race/ethnicity as proxy
      indicators of complex health determinants, and should aim at dissecting these
      determinants into separate items. Careful documentation of methodology and active
      involvement of the minorities themselves can increase trust between the
      investigators and the research subjects, which can in turn improve research on
      minority health.

PMID- 17435437
TI  - Environmental exposure to confined animal feeding operations and respiratory
      health of neighboring residents.
AB  - BACKGROUND: Despite public concern about potential adverse health effects of
      concentrated animal feeding operations, objectively assessed data on
      environmental exposure to concentrated animal feeding operations and respiratory
      health are sparse. We aimed to assess respiratory health in neighbors of confined
      animal feeding operations. METHODS: A survey was done in 2002-2004 among all
      adults (18-45 years old) living in 4 rural German towns with a high density of
      confined animal feeding operations. Questionnaire data were available for 6937
      (68%) eligible subjects. In a random sample we measured the following outcomes:
      specific IgE to common and farm-specific allergens, lung function, and bronchial
      hyperresponsiveness to methacholine. Exposure was measured by collecting data on
      odor annoyance and geo-coded data on the number of animal houses within 500 m of
      the home. Locally optimal estimating and smoothing scatter plots were used to
      model the association between exposure and outcome. Analyses were restricted to
      subjects without private or professional contact with farming environments.
      RESULTS: The prevalence of self-reported asthma symptoms and nasal allergies
      increased with self-reported odor annoyance. The number of animal houses was a
      predictor of self-reported wheeze and decreased forced expiratory volume in 1
      second, but not allergic rhinitis or specific sensitization. Self-reported
      exposure and results of clinical measurements were poorly correlated.
      CONCLUSIONS: Confined animal feeding operations may contribute to the burden of
      respiratory disease among their neighbors. Our findings underline the importance
      of objective assessment of exposure and outcome in environmental epidemiology.

PMID- 17435438
TI  - Environmental exposure and health effects from concentrated animal feeding
      operations.
AB  - Modern concentrated animal feeding operations generate sizeable amounts of manure
      and related emissions into water and air. These present potential harm to human
      health. Adverse respiratory effects have been documented among workers in these
      feeding operations, but there has been little research on wider environmental
      effects. Few conclusions are possible at this time but recent studies (including
      a report in this issue of Epidemiology by Radon and colleagues) suggest possible
      adverse effects. Respiratory outcomes of greatest concern include nasal
      allergies, airflow obstruction and asthma. Another concern among residents near
      concentrated animal feeding operations is adverse effects from malodors. The
      potential impact of these operations on quality of life and health needs to be
      documented.

PMID- 17435439
TI  - Neurobehavioral development in children with potential exposure to pesticides.
AB  - BACKGROUND: Children may be at higher risk than adults from pesticide exposure,
      due to their rapidly developing physiology, unique behavioral patterns, and
      interactions with the physical environment. This preliminary study conducted in
      Ecuador examines the association between household and environmental risk factors
      for pesticide exposure and neurobehavioral development. METHODS: We collected
      data over 6 months in the rural highland region of Cayambe, Ecuador (2003-2004).
      Children age 24-61 months residing in 3 communities were assessed with the Ages
      and Stages Questionnaire and the Visual Motor Integration Test. We gathered
      information on maternal health and work characteristics, the home and community
      environment, and child characteristics. Growth measurements and a hemoglobin
      finger-prick blood test were obtained. Multiple linear regression analyses were
      conducted. RESULTS: Current maternal employment in the flower industry was
      associated with better developmental scores. Longer hours playing outdoors were
      associated with lower gross and fine motor and problem solving skills. Children
      who played with irrigation water scored lower on fine motor skills (8% decrease;
      95% confidence interval = -9.31 to -0.53), problem-solving skills (7% decrease; 
      8.40 to -0.39), and Visual Motor Integration test scores (3% decrease; -12.00 to
      1.08). CONCLUSIONS: These results suggest that certain environmental risk factors
      for exposure to pesticides may affect child development, with contact with
      irrigation water of particular concern. However, the relationships between these
      risk factors and social characteristics are complex, as corporate agriculture may
      increase risk through pesticide exposure and environmental contamination, while
      indirectly promoting healthy development by providing health care, relatively
      higher salaries, and daycare options.

PMID- 17435440
TI  - Combining internal and external validation data to correct for exposure
      misclassification: a case study.
AB  - Internal validation data offer a well-recognized means to help correct for
      exposure misclassification or measurement error. When available, external
      validation data offer the advantage of cost-effectiveness. However, external data
      are a generally inefficient source of information about misclassification
      parameters. Furthermore, external data are not necessarily "transportable", for
      example, if there are differences in the design or target populations of the main
      and validation studies. Recent work has suggested weighted estimators to
      simultaneously take advantage of internal and external validation data. We
      explore efficiency and transportability in the fundamental case of estimating the
      odds ratio for binary exposure in a case-control setting. Our results support the
      use of closed-form weighted log odds ratio estimators in place of computationally
      demanding maximum likelihood estimators under both types of validation study
      designs (using internal data only, and combining internal and external data). We
      also provide and assess a formal test of the transportability assumption, and
      introduce a new log odds ratio estimator that is inherently robust to violation
      of that assumption. A case-control study of the association between maternal
      antibiotic use and sudden infant death syndrome provides a real-data example.

PMID- 17435441
TI  - The identification of synergism in the sufficient-component-cause framework.
AB  - Various concepts of interaction are reconsidered in light of a sufficient
      component-cause framework. Conditions and statistical tests are derived for the
      presence of synergism within sufficient causes. The conditions derived are
      sufficient but not necessary for the presence of synergism. In the context of
      monotonic effects, the conditions derived are closely related to effect
      modification on the risk difference scale; however, this is not the case without
      the assumption of monotonic effects.

PMID- 17435442
TI  - Risk factors for positive tuberculin skin test in Guinea-Bissau.
AB  - BACKGROUND: The tuberculin skin test is used for tracing of tuberculosis
      transmission and identifying individuals in need of prophylactic treatment.
      METHODS: Using a case-control study design, we recruited 220 smear-positive
      tuberculosis cases and 223 randomly selected healthy community controls in
      Bissau, Guinea-Bissau, during 1999-2000. Tuberculin skin tests were performed on
      family members of cases and controls (n = 1059 and n = 921, respectively).
      Induration of 10 mm or greater was considered positive. Risk factors were
      calculated for children (<15 years) and adults separately in multivariate
      logistic regression analysis. RESULTS: The prevalence of positive tuberculin skin
      test was 41% in case-contacts compared with 22% in control-contacts, resulting in
      a prevalence ratio of 1.48 (95% confidence interval = 1.37-1.60). Positive skin
      tests among case-contacts increased with age for children, as well as with
      proximity to a case during the night, for both children and adults. A Bacille
      Calmette Guerin scar increased the likelihood of having a positive tuberculin
      skin test for adults in case households, but not in other categories of contacts.
      Among control-contacts the prevalence of positive skin test was associated with
      older age in children, history of tuberculosis in the family, and a positive
      tuberculin skin test of the control person. CONCLUSIONS: Risk factors for a
      positive tuberculin skin test among case- and control-contacts are closely
      related to tuberculosis exposure. Having a BCG scar did not increase the risk of
      positive skin test in unexposed individuals. Tuberculin skin testing remains a
      useful tool for diagnosing tuberculosis infection.

PMID- 17435443
TI  - Tuberculin testing to detect latent tuberculosis in developing countries.
AB  - Despite the multiple studies done over several decades that have established the
      utility of the tuberculin skin test (TST) for the diagnosis of latent
      tuberculosis, the test is rarely used in developing countries experiencing a
      resurgence of tuberculosis. Nevertheless, several clinical trials have found that
      treatment of HIV-positive or HIV-negative persons with latent tuberculosis is
      effective in the prevention of the clinical activation of tuberculosis.
      Clinicians commonly justify their failure to diagnose and treat latent
      tuberculosis with the belief that BCG vaccine, even when it is used in infancy,
      will cause false positive reactivity in the TST. The important study by Gustafson
      and colleagues from Guinea-Bissau in this issue of the journal refutes this
      belief. In this study only persons with a history of BCG who also had household
      contact with an active case of tuberculosis had increased rates of TST
      positivity. Although the current emphasis is on directly observed therapy, short
      course (DOTS) to control tuberculosis is necessary and critically important, it
      is not always sufficient to control the tuberculosis epidemic in some countries
      with major epidemics of HIV. In many of these countries, early diagnosis of
      active tuberculosis and prevention of activation of latent tuberculosis will also
      be needed. The evidence from the Guinea-Bissau study suggests that a history of
      BCG vaccination should not be an obstacle to the diagnosis and treatment of
      latent tuberculosis.

PMID- 17435444
TI  - Work schedule during pregnancy and spontaneous abortion.
AB  - BACKGROUND: There is inconsistent evidence as to whether work schedule (including
      rotating shifts and night work) can affect reproductive outcomes. METHODS: We
      investigated the association between work schedule and risk of spontaneous
      abortion in U.S. nurses. The Nurses' Health Study II is a prospective cohort
      study established in 1989. In 2001, information about occupational activities and
      exposures during pregnancy was collected from female nurses for the most recent
      pregnancy since 1993. Of 11,178 eligible respondents, 9547 (85%) indicated
      willingness to participate in the occupational study, and 8461 of those (89%)
      returned the questionnaire, for an overall participation rate of 76%. Of these,
      7688 women had pregnancies that were eligible for analysis. RESULTS: Participants
      reported 6902 live births and 786 (10%) spontaneous abortions. Compared with
      women who reported usually working "days only" during their first trimester,
      women who reported usually working "nights only" had a 60% increased risk of
      spontaneous abortion (RR = 1.6; 95% confidence interval [CI] = 1.3-1.9). A
      rotating schedule, with or without night shifts, was not associated with an
      increase in risk (RR = 1.2 [CI = 0.9-1.5] and 1.0 [CI = 0.8-1.2], respectively).
      Women who reported working more than 40 hours per week during the first trimester
      were also at increased risk of spontaneous abortion (1.5; 1.3-1.7) compared with
      women working 21-40 hours, even after adjustment for work schedule. CONCLUSIONS:
      Nightwork and long work hours may be associated with an increased risk of
      spontaneous abortion. Further studies are needed to determine whether hormonal
      disturbances attributed to night work affect pregnancy outcome.

PMID- 17435445
TI  - Maternal stressful life events and risks of birth defects.
AB  - BACKGROUND: Several previous studies suggest that maternal stress may be
      associated with increased risk of certain birth defects. This study examined the
      association of maternal stressful life events with risks of several birth
      defects. METHODS: The data are from a recent, population-based case-control
      study. Telephone interviews were conducted with 1355 eligible case mothers and
      700 control mothers. Maternal stress was measured by responses to 18 yes/no
      questions about life events that occurred from 2 months before through 2 months
      after conception. RESULTS: An increase in the stressful life events index (ie,
      number of "yes" responses to the 18 life-events questions) was associated with
      increased risk of cleft palate, cleft lip with or without cleft palate, d
      transposition of the great arteries, and tetralogy of Fallot, after adjustment
      for maternal race-ethnicity, education, obesity, age, smoking, drinking, intake
      of folic acid-containing supplements, neighborhood crime, and food insecurity.
      For example, the odds ratio for a 3-unit change in the stress index was 1.45 (95%
      confidence interval = 1.03-2.06) for cleft palate. Increased stress was
      associated with an increased risk of spina bifida and anencephaly particularly
      among women who did not take folic acid supplements. A 3-unit change in stress
      was associated with a 2.35-fold increased risk of anencephaly among women who did
      not take supplements (CI =1.47-3.77) and a 1.42-fold increased risk among women
      who did (CI = 0.89-2.25). CONCLUSION: The adverse health effects of stress may
      include increased risks of certain birth defects.

PMID- 17435446
TI  - When will we eliminate folic acid-preventable spina bifida?
AB  - Mandatory vitamin B12 fortification of enriched grain products is long overdue in
      the United States and Canada. Fortification would help provide the 2.4 mug of
      synthetic vitamin B12 that the US Institute of Medicine recommends for all
      persons 50 years and older. The findings of Ray and colleagues in this issue
      suggest that B12 may also help to prevent neural tube defects. If recommendations
      for B12 fortification were followed, it is possible that cases of spina bifida
      and anencephaly would be prevented. Two hundred twenty thousand children each
      year acquire folic acid-preventable spina bifida because many governments,
      including all in Europe, have yet to implement mandatory folic acid
      fortification. Fortification with folic acid and vitamin B12 is safe and should
      be implemented in all countries.

PMID- 17435447
TI  - Temperature and cardiovascular deaths in the US elderly: changes over time.
AB  - BACKGROUND: Short-term changes in temperature have been associated with
      cardiovascular deaths. This study examines changes in this association over time
      among the US elderly. METHODS: Daily cardiovascular mortality counts from 107
      cities in the US National Morbidity and Mortality Air Pollution Study were
      regressed against daily temperature using the case-crossover method. Estimates
      were averaged by time and season using a meta-analysis. RESULTS: In summer 1987
      the average increase in cardiovascular deaths due to a 10 degrees F increase in
      temperature was 4.7%. By summer 2000, the risk with higher temperature had
      disappeared (-0.4%). In contrast, an increase in temperature in fall, winter and
      spring was associated with a decrease in deaths, and this decrease remained
      constant over time. CONCLUSIONS: Heat-related cardiovascular deaths in the
      elderly have declined over time, probably due to increased use of air
      conditioning, while increased risks with cold-related temperature persist.

PMID- 17435448
TI  - Cooked meat and risk of breast cancer--lifetime versus recent dietary intake.
AB  - BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines
      (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at
      high temperature. METHODS: We estimated breast cancer risk in relation to intake
      of cooked meat in a population-based, case-control study (1508 cases and 1556
      controls) conducted in Long Island, NY from 1996 to 1997. Lifetime intakes of
      grilled or barbecued and smoked meats were derived from the interviewer
      administered questionnaire data. Dietary intakes of PAH and HCA were derived from
      the self-administered modified Block food frequency questionnaire of intake 1
      year before reference date. Unconditional logistic regression was used to
      estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:
      Modest increased risk was observed among postmenopausal, but not premenopausal,
      women consuming the most grilled or barbecued and smoked meats over the life
      course (OR = 1.47; CI = 1.12-1.92 for highest vs. lowest tertile of intake).
      Postmenopausal women with low fruit and vegetable intake, but high lifetime
      intake of grilled or barbecued and smoked meats, had a higher OR of 1.74 (CI =
      1.20-2.50). No associations were observed with the food frequency questionnaire
      derived intake measures of PAHs and HCAs, with the possible exception of
      benzo(alpha)pyrene from meat among postmenopausal women whose tumors were
      positive for both estrogen receptors and progesterone receptors (OR = 1.47; CI =
      0.99-2.19). CONCLUSIONS: These results support the accumulating evidence that
      consumption of meats cooked by methods that promote carcinogen formation may
      increase risk of postmenopausal breast cancer.

PMID- 17435449
TI  - Occupational exposures and breast cancer among women textile workers in Shanghai.
AB  - BACKGROUND: Breast cancer incidence rates have been increasing in China over the
      past 2 decades. Most studies have focused on reproductive, dietary, and genetic
      risk factors. Little is known about the contribution of occupational exposures.
      METHODS: We conducted a case-cohort study within a cohort of female textile
      workers who had participated in a randomized trial of breast self-examination in
      Shanghai, China. We compared 1709 incident breast cancer cases with an age
      stratified reference subcohort (n = 3155 noncases). Cox proportional hazards
      modeling, adapted for the case-cohort design, was used to estimate hazard ratios
      for breast cancer in relation to duration of employment in various job processes
      and duration of exposure to several agents. We also evaluated the associations of
      cotton dust and endotoxin with breast cancer. RESULTS: Cumulative exposures to
      cotton dust and endotoxin demonstrated strong inverse gradients with breast
      cancer risk when exposures were lagged by 20 years (trend P-values <0.001). We
      did not observe consistent associations with exposures to electromagnetic fields,
      solvents, or other chemicals. CONCLUSION: Endotoxin or other components of cotton
      dust exposures may have reduced risks for breast cancer in this cohort, perhaps
      acting at early stages of carcinogenesis. Replication of these findings in other
      occupational settings with similar exposures will be needed to confirm or refute
      any hypothesis regarding protection against breast cancer.

PMID- 17435450
TI  - A prospective study of dietary patterns and mortality in Chinese women.
AB  - BACKGROUND: Many foods and nutrients have been suggested to influence life
      expectancy. However, previous studies have not examined the relationship between
      dietary patterns and cause-specific mortality. Our study prospectively examines
      the relationship of dietary patterns with total mortality and cause-specific
      mortality in a population-based cohort study of Chinese women. METHODS: The
      Shanghai Women's Health Study is a population-based cohort study of 74,942 women
      age 40 to 70 years at the time of recruitment (September 1996 to May 2000).
      Detailed dietary information was collected using a validated, quantitative food
      frequency questionnaire. The cohort has been followed using a combination of in
      person interviews and record linkage with various registries. Dietary patterns,
      derived from principal component analysis, were examined for their relation to
      total mortality and cause-specific mortality using Cox regression models.
      RESULTS: After an average of 5.7 years of follow-up (423,717 person-years of
      observation), there were 1565 deaths. We derived 3 major dietary patterns
      (vegetable-rich, fruit-rich, and meat-rich). The adjusted hazard ratios for the
      fruit-rich diet were 0.94 (95% CI = 0.89-0.98) for all causes of death and 0.89
      (0.81-0.99), 0.79 (0.69-0.91), and 0.51 (0.39-0.65) for death caused by
      cardiovascular disease, stroke, and diabetes, respectively. The meat-rich diet
      was associated with increased risk of diabetes (HR = 1.18; 95% CI = 0.98-1.42)
      and a slightly elevated risk of total mortality. CONCLUSION: In general, a fruit
      rich diet was related to lower mortality, whereas a meat-rich diet appeared to
      increase the probability of death.

PMID- 17435452
TI  - SSRIs and birth defects.

PMID- 17435453
TI  - Lower limb cellulitis after a typhoon and flood.

PMID- 17435454
TI  - SSRIs and birth defects.

PMID- 17435456
TI  - Janet Lane-Claypon.

PMID- 17435458
TI  - Effect of supplementation with polyunsaturated fatty acids and micronutrients on
      learning and behavior problems associated with child ADHD.
AB  - METHODS: Various developmental problems including attention-deficit/hyperactivity
      disorder (ADHD) have been linked to biological deficiencies in polyunsaturated
      fatty acids (PUFAs). Additionally, there is evidence that symptoms may be reduced
      with PUFA supplementation. This study investigated effects of supplementation
      with PUFAs on symptoms typically associated with ADHD. Because nutrients work
      synergistically, additional effects of micronutrient supplementation were also
      investigated. A total of 132 Australian children aged 7 to 12 years with scores >
      or = 2 SD above the population average on the Conners ADHD Index participated in
      a randomized, placebo-controlled, double-blind intervention over 15 weeks, taking
      PUFAs alone, PUFAs + micronutrients, or placebo. Due to unreturned
      questionnaires, data were only available for 104 children. RESULTS: Significant
      medium to strong positive treatment effects were found on parent ratings of core
      ADHD symptoms, inattention, hyperactivity/impulsivity, on the Conners Parent
      Rating Scale (CPRS) in both PUFA treatment groups compared with the placebo
      group; no additional effects were found with the micronutrients. After a one-way
      crossover to active supplements in all groups for a further 15 weeks, these
      results were replicated in the placebo group, and the treatment groups continued
      to show significant improvements on CPRS core symptoms. No significant effects
      were found on Conners Teacher Rating Scales. CONCLUSION: These results add to
      preliminary findings that ADHD-related problems with inattention, hyperactivity,
      and impulsivity might respond to treatment with PUFAs and that improvements may
      continue with supplementation extending to 30 weeks.

PMID- 17435459
TI  - Developmental and behavioral comorbidities of asthma in children.
AB  - OBJECTIVE: Asthma is the most common chronic childhood illness. Treatment is
      typically focused on disease management rather than developmental and behavioral
      comorbidities that may affect quality of life or contribute to poor disease
      control. The purpose of this study was to explore the prevalence of developmental
      and behavioral comorbidities of asthma and the role of confounding socioeconomic
      factors. METHODS: The first National Survey of Children's Health was the data
      source for this study. Interviews with parents or guardians were conducted during
      2003-2004 to ascertain the physical, emotional, and behavioral health of 102,353
      randomly selected children ages 0-17 years. Associations were examined between
      asthma and rates of developmental and behavioral problems. Logistic regression
      was used to adjust for potential confounding effects of age, gender, race,
      income, and parent education on outcomes. RESULTS: Children with asthma have
      higher rates of attention-deficit/hyperactivity disorder; diagnoses of
      depression, behavioral disorders, learning disabilities; and missed school days
      (all p < .0001). The more severe the asthma is, the higher the rates are of these
      problems. Children with asthma are bullied more commonly and are more likely to
      abuse drugs. When socioeconomic factors are controlled for, asthma significantly
      increases the odds of having developmental, emotional, and behavioral problems.
      CONCLUSIONS: Children with asthma, especially severe asthma, are at high risk of
      developmental, emotional, and behavioral problems. Asthma is independently
      associated with these problems, although socioeconomic disadvantage adds
      additional risk. Asthma treatment programs must acknowledge and address these
      comorbidities to achieve the best overall outcomes for children with this common
      chronic disease.

PMID- 17435460
TI  - The impact of child care providers' feeding on children's food consumption.
AB  - BACKGROUND: In young children, the eating environment is an important social
      context within which eating behaviors develop. Among many low-income young
      children, the responsibility for feeding may have shifted from family members to
      child care providers because these children spend the majority of their day in
      child care settings. METHODS: To examine the influence of feeding among low
      income children in child care settings, feeding behaviors of child care providers
      in Head Start were observed and food consumption was assessed. Head Start, a
      comprehensive child development program that serves children from ages 3 to 5,
      was chosen because of the large percentage of minorities, the low-income status
      of the families, and the age of the children. Fifty child care providers (25
      African-American; 25 Hispanic) randomly selected from Head Start centers in a
      large, urban southwestern city were observed on three mealtime occasions and self
      reported feeding styles were assessed. Observed feeding behaviors were
      categorized into four feeding patterns based on their conceptual similarity to a
      general parenting typology (i.e., authoritarian, authoritative, indulgent, and
      uninvolved). Measures of food consumption were assessed on 549 children sitting
      with the child care providers during lunch at the Head Start centers. RESULTS:
      Indulgent feeding behaviors were positively related to children's consumption of
      vegetables, dairy, entree, and starch; authoritative feeding behaviors were
      positively related to dairy consumption. CONCLUSION: This research highlights the
      important influence that child care providers have in the development of healthy
      and unhealthy eating behaviors in minority children. Implications for
      intervention training for child care providers to promote healthy eating among
      Head Start children are discussed.

PMID- 17435461
TI  - Symptoms of attention-deficit/hyperactivity disorder following traumatic brain
      injury in children.
AB  - METHODS: We investigated changes in inattentive and hyperactive symptoms over 2
      years following traumatic brain injury (TBI) in relation to preinjury attention
      deficit/hyperactivity disorder (ADHD), injury, and socioeconomic status (SES)
      variables. Postinjury stimulant medication treatment was also documented. Of 175
      consecutive patients of ages 5 to 15 years with acute TBI, 148 consented,
      including 114 without preinjury ADHD (mean age, 10.0 years, SD = 2.76) and 34
      with preinjury ADHD (mean age 10.36 years, SD = 2.75). The Schedule for Affective
      Disorders and Schizophrenia for School-Age Children, Present and Lifetime
      Version, was administered at baseline and at 6, 12, and 24 months post-injury to
      assess the presence of nine core inattentive and nine hyperactive symptoms and
      associated impairment. The baseline assessment was performed within 1 month post
      injury to establish preinjury diagnosis. RESULTS: Nonlinear change in inattentive
      symptoms in patients without preinjury ADHD contrasted with higher and more
      stable symptom levels in children with preinjury diagnosis, including the cubic
      trend (chi2(1) = 6.23, p = .0126). There was also a significant interaction of
      group x gender effect (chi2(1) = 4.08, p = .0435) as males had higher numbers of
      inattentive symptoms than females in the preinjury ADHD group. Change in
      hyperactive symptoms over time also differed by group, including both linear
      (chi2(1) = 5.42, p = .0199) and cubic trends (chi2(1) = 8.91, p = .0029),
      reflecting greater and more frequent fluctuations in children without preinjury
      ADHD. Socioeconomic level also contributed to change in hyperactive symptoms as
      reflected by the interaction of SES and linear time (chi2(1) = 6.91, p = .009),
      as well as quadratic time (chi2(1) = 4.90, p = .027). Occurrence of ADHD
      diagnosed post-injury ranged from 14.5% (12 months) to 18.3% (24 months) in the
      group without preinjury ADHD compared with a range from 86.4% (12 months) to
      96.2% (6 months) in children with preinjury ADHD. In children without preinjury
      ADHD, SES was the only patient variable that predicted onset of ADHD, t(110) = 
      2.85, p = .0052. Treatment with stimulant medication post-injury was more
      frequently associated with preinjury ADHD (39% vs 7% of children without
      preinjury ADHD), p< .0001 (Fisher exact test). Children with preinjury ADHD who
      were treated pre-injury with stimulant medication had fewer total symptoms at 24
      months post-injury relative to untreated patients with preinjury ADHD (F[1,14] =
      3.93, p = 0.069, Cohen's d = 1.28). CONCLUSION: Change in ADHD symptoms after TBI
      varies with preinjury diagnosis, reflects injury severity in children without
      preinjury ADHD, and is treated with stimulant medication mainly in those patients
      with preinjury ADHD.

PMID- 17435462
TI  - 22q11.2DS deletion syndrome: developmental milestones in infants and toddlers.
AB  - BACKGROUND: The majority of children with 22q11.2DS deletion syndrome (22q11.2DS)
      have learning disabilities, and a substantial number have mental retardation.
      Although cognitive data have been reported on several samples of children with
      22q11.2DS, data on their early developmental milestones are limited. METHODS: The
      present study used a retrospective design and asked parents to recall
      developmental milestones. The participants were 88 children with 22q11.2DS, 47
      community controls, and 29 sibling controls. RESULTS: Although very early gross
      motor and expressive language milestones did not differ significantly from
      comparison groups, subsequent gross motor and expressive language milestones did,
      suggesting that children with 22q11.2DS may begin to lag behind their peers
      sometime after the first year of life in these two domains. These patterns were
      also apparent when a subset of intellectually comparable children (22q11.2DS, n =
      40 vs community controls, n = 24) was analyzed. We further found that receptive
      language and social adaptive milestones did not differ from comparison samples in
      either the early or later period. Receptive language delays were predictive of
      later Wechsler Intelligence Scale for Children-Third Edition Perceptual
      Organization Index scores, particularly in girls with 22q11.2DS. CONCLUSIONS:
      This suggests that although receptive language may be an area of relative
      strength in the developmental profile of young children with 22q11.2DS, even mild
      receptive delays should not be overlooked in early interventions with children
      with this disorder.

PMID- 17435463
TI  - Psychometric properties of the Peer Interactions in Primary School (PIPS)
      Questionnaire.
AB  - BACKGROUND: Recently, national and international scientific and popular press has
      focused on bullying and victimization. Unfortunately, many interventions that
      address bullying and victimization are yet to be empirically validated. One
      problem is the lack of a psychometrically sound instrument for the measurement of
      bullying and victimization. METHODS: To alleviate this shortcoming, the Peer
      Interactions in Primary School Questionnaire (PIPS) was developed and tested.
      Twenty-two questions designed to capture direct and indirect forms of bullying
      and victimization were created at a third-grade reading level. Psychometric data
      were collected from administration of the questionnaire to 270 students in third
      through sixth grades at three different elementary schools. An exploratory factor
      analysis yielded two factors (bullying and victimization). RESULTS: Internal
      consistency for the questionnaire was high (Cronbach's alpha = .90). Intraclass
      correlation coefficients (ICCs) and Spearman's rho established that test-retest
      reliability was high for both scales: bullying (ICC = .84; rho = .76) and
      victimization (ICC = .88; rho = .87). Significant Kruskal-Wallis tests of
      relationships between PIPS scales and items on the Olweus Bullying/Victimization
      Questionnaire and the Strengths and Difficulties Questionnaire supported
      concurrent validity. Bullying and victimization were widespread, as 89.5% of
      children experienced some form of victimization and 59.0% of students
      participated in some form of bullying. CONCLUSION: With these data, the PIPS is
      the first self-report bullying and victimization measure designed for elementary
      school use determined reliable (internally consistent and reproducible) and
      valid. The PIPS is a tool that could be used in the design and evaluation of
      school-based bullying/victimization interventions.

PMID- 17435464
TI  - The Prader-Willi phenotype of fragile X syndrome.
AB  - The Prader-Willi phenotype (PWP) of fragile X syndrome (FXS) is associated with
      obesity and hyperphagia similar to Prader-Willi syndrome (PWS), but without
      cytogenetic or methylation abnormalities at 15q11-13. Thirteen cases of PWP and
      FXS are reported here that were identified by obesity and hyperphagia. Delayed
      puberty was seen in 5 of 9 cases who had entered puberty, a small penis or
      testicles in seven of 13 cases, and infant hypotonia and/or a poor suck in seven
      of 13 cases. Autism spectrum disorder occurred in 10 of 13 cases, and autism was
      diagnosed in seven of 13 cases. We investigated cytoplasmic interacting FMR1
      protein (CYFIP) expression, which is a protein that interacts with FMR1 protein
      (FMRP) because the gene for CYFIP is located at 15q11-13. CYFIP mRNA levels were
      significantly reduced in our patients with the PWP and FXS compared to
      individuals without FXS (p < .001) and also individuals with FXS without PWP (p =
      .03).

PMID- 17435465
TI  - Polyunsaturated fatty acid supplementation for ADHD? Fishy, fascinating, and far
      from clear.

PMID- 17435467
TI  - Effect-size measures and research in developmental and behavioral pediatrics.

PMID- 17435469
TI  - A 7-year-old child with Down syndrome and disruptive behaviors.

PMID- 17435473
TI  - Disclosure of an HIV diagnosis to children: history, current research, and future
      directions.
AB  - Disclosing the diagnosis of human immunodeficiency virus (HIV) or AIDS to a child
      is a controversial and emotionally charged issue among both the health care
      communities and parents and caregivers of these children. This paper provides a
      systematic review of research on disclosure of pediatric HIV infection. It begins
      with a brief discussion of disclosure drawing from research on pediatric cancer.
      Next, we review the available research including patterns of disclosure, factors
      associated with disclosure and nondisclosure, and the effect of disclosure on
      psychological health and adherence. A review of published intervention studies is
      also included. While no consensus on when the diagnosis of HIV should be
      disclosed to a child or the psychological outcomes associated with disclosure was
      found, clinical consensus on several issues related to working with families was
      identified. We apply this literature to clinical practice and suggest avenues and
      directions for future research.

PMID- 17435474
TI  - Society for Developmental and Behavioral Pediatrics 2006 presidential address:
      Coming full circle: reflections at the interface of developmental-behavioral and
      general pediatrics.

PMID- 17435476
TI  - Knowing what others know, feeling what others feel: a controlled study of empathy
      in psychotherapists.
AB  - There has been considerable interest in assessing whether psychotherapists have
      enhanced abilities in empathy and whether those abilities influence treatment
      outcomes. However, to date, studies have been hindered by inconsistent
      definitions of empathy and a reliance on assessment via self-report. The unique
      aim of this study was to ascertain the empathic abilities of psychotherapists
      using a multidimensional battery consisting of objective and self-report
      measures. We compared 19 therapists and 19 well-matched control subjects on
      several measures of empathy. On tests emphasizing the cognitive aspects of
      empathy, therapists were no different from controls when making inferences based
      on facial expressions but were significantly better when making inferences based
      on language. On a test emphasizing the emotional aspects of empathy, therapists
      did not report to be more empathically concerned than controls; however, on a
      test of emotion regulation, they reported less personal distress in response to
      the distress of others. In sum, therapists were better able to interpret the
      verbal cues of others and described themselves as more emotionally controlled in
      response to tense interpersonal situations.

PMID- 17435477
TI  - Depersonalization experiences in undergraduates are related to heightened stress
      cortisol responses.
AB  - The relationship between dissociative tendencies, as measured with the
      Dissociative Experiences Scale and its amnesia, absorption/imaginative
      involvement, and depersonalization/derealization subscales, and HPA axis
      functioning was studied in 2 samples of undergraduate students (N = 58 and 67).
      Acute stress was induced by means of the Trier Social Stress Test. Subjective and
      physiological stress (i.e., cortisol) responses were measured. Individuals high
      on the depersonalization/derealization subscale of the Dissociative Experiences
      Scale exhibited more pronounced cortisol responses, while individuals high on the
      absorption subscale showed attenuated responses. Interestingly, subjective stress
      experiences, as indicated by the Tension-Anxiety subscale of the Profile of Mood
      States, were positively related to trait dissociation. The present findings
      illustrate how various types of dissociation (i.e.,
      depersonalization/derealization, absorption) are differentially related to
      cortisol stress responses.

PMID- 17435478
TI  - Comparing psychological distress, traumatic stress reactions, and experiences of
      unaccompanied refugee minors with experiences of adolescents accompanied by
      parents.
AB  - The objective of this study is to make comparisons of the severity of the
      psychological distress, behavioral problems and traumatic stress reactions, and
      experiences of unaccompanied refugee minors (URMs) with immigrant/refugee (I/R)
      and Dutch (native) adolescents with parental caregivers (N = 3273). Self-report
      questionnaires were administered. Most assessments took place at school. URMs
      consistently reported significantly higher scores for internalizing problems,
      traumatic stress reactions, and stressful life events than all other groups.
      Gender appears to play an important role in the native and I/R samples in
      reporting psychological distress, behavioral problems, and traumatic stress
      reactions. Older age was significantly related to higher scores only in the URM
      group. Natives scored higher on externalizing problems than the other groups.
      URMs reported to have experienced twice as many stressful life events than I/Rs
      and natives. URMs appear to be at significantly higher risk for the development
      of psychopathology than refugee adolescents living with a family member,
      immigrants, or Dutch adolescents.

PMID- 17435479
TI  - Change in prevalence of psychiatric disorders from ages 21 to 30 in a community
      sample.
AB  - The authors examined change and demonstrated variation in the prevalence of
      psychiatric disorders from ages 21 to 30 in a prospective community study (n =
      352) using generalized estimating equations and investigated effects of past and
      recent psychiatric disorder on emerging adult functioning (at age 30). Results
      revealed significant declines in 12-month prevalence of phobia and substance use
      disorders from ages 21 to 30 but not in depression or posttraumatic stress
      disorder. Males were at significantly higher risk for lifetime substance use
      disorders; females were at higher risk for lifetime depression, phobia, and PTSD.
      Twelve-month and lifetime disorder were associated with impaired global
      functioning at age 30. Internalizing disorders were associated with impaired
      interpersonal functioning, whereas externalizing disorders were associated with
      impaired socioeconomic functioning. Results of this study have implications for
      mental health service planning in emerging adulthood.

PMID- 17435480
TI  - The role of substance use in families' attributions and affective reactions to
      their relative with severe mental illness.
AB  - This study compared relatives' attributions and affective reactions toward
      patients with severe mental illness (SMI) only (N = 32) and patients with dual
      SMI and a substance use disorder (N = 36). Family members of patients with dual
      disorders perceived their ill relatives to have greater control over the causes
      of their psychiatric symptoms and to be more responsible for their symptoms than
      did family members of patients with SMI only. Key relatives of dual-diagnosed
      patients also reported more negative affect toward the patient than did key
      relatives of patients with SMI only, but the two groups did not differ in their
      level of positive affect. Consistent with attribution theory, severity of
      patients' substance abuse was positively associated with relatives' attributions
      of controllability, which, in turn, were positively associated with judgments of
      responsibility. Furthermore, judgments of responsibility were positively related
      to negative affect and inversely related to positive affect.

PMID- 17435481
TI  - Late-onset schizophrenia in child survivors of the holocaust.
AB  - According to the stress diathesis model, the probability of psychosis is
      increased in high-risk groups, a vulnerable one being the Holocaust child
      survivors. This study was conducted to inquire into the long-term effects of
      their Holocaust experience. We concentrated on a possible association between the
      onset of schizophrenia and the degree of persecution. Ninety-three medical files
      of Holocaust child survivors were recruited from sociomedical expert reports of
      the Restitution Office in Germany. The onset of schizophrenia was used as
      dependent variable in a categorical regression model. Regarding schizophrenia,
      exclusively late-onset schizophrenia could be diagnosed in our sample.
      Schizophrenia was significantly associated with the highest category of
      persecution (Fisher exact test, p < 0.001). In the categorical regression model,
      the category of persecution was a significant coefficient, only (F = 23.9, p <
      0.001). The strong association between late onset of schizophrenia and the degree
      of persecution suggest an influence of stress exposure.

PMID- 17435482
TI  - Measuring anxiety in patients with schizophrenia.
AB  - This study describes the prevalence and distribution of anxiety symptomatology
      and anxiety disorders in a sample of hospitalized patients with schizophrenia,
      the estimated level of agreement between a clinician diagnostic measure and
      anxiety symptom status measures, and their internal consistency based on the
      average interitem correlations. Seventy inpatients receiving treatment for
      schizophrenia were assessed before discharge using a face-to-face diagnostic
      interview and structured questionnaires, namely the Mini International
      Neuropsychiatric Interview, the Hospital Anxiety and Depression Scale, the
      Hamilton Anxiety Scale, the Spielberger Anxiety Inventory, and the Stein
      Generalized Anxiety Disorder (GAD) Scale. About a quarter of patients met
      criteria for an anxiety disorder, with GAD and social phobia occurring most
      commonly. There was poor agreement between the Mini International
      Neuropsychiatric Interview and a diagnosis of anxiety based on symptom status
      measures. The Stein GAD scale demonstrated the highest internal consistency
      (0.85) followed by the Hamilton Anxiety Scale (0.76). Anxiety disorders and
      anxiety symptomatology are highly prevalent in schizophrenia. Accurate assessment
      is challenging yet important. More reliable measures of anxiety disorders in
      patients with schizophrenia and other psychotic disorders are clearly needed to
      allow for timely identification and treatment.

PMID- 17435483
TI  - Humor appreciation deficit in schizophrenia: the relevance of basic
      neurocognitive functioning.
AB  - The purpose in undertaking the present study was to investigate humor
      appreciation in patients with schizophrenia. Moreover, we sought to explore the
      potential relationship of humor appreciation with measures of psychopathology and
      cognitive functioning among the patients. Thirty-six patients with schizophrenia
      were compared with 31 normal controls matched for age, sex, and education on a
      computerized test comprising captionless cartoons: Penn's Humor Appreciation Test
      (PHAT). The patients were also evaluated on the symptom dimensions derived from
      the Positive and Negative Symptom Scale (positive symptoms, negative symptoms,
      cognitive symptoms, depression, and excitement), as well as a battery of
      neuropsychological tests measuring executive functions, attention, working
      memory, verbal and visual memory, visuospatial ability, and psychomotor speed.
      Patients with schizophrenia had significantly lower scores on the PHAT than
      normal controls. The patients' performance on the PHAT correlated with scores on
      Penn's Continuous Performance Test, the Stroop Color-Word Test, and the
      phonological subscale of the Greek Verbal Fluency Test. Our findings indicated
      impaired humor appreciation among patients with schizophrenia. The relationship
      found between the appreciation of captionless cartoons involved an incongruous
      detail and performance on a broad neuropsychological battery suggested that the
      deficit in humor appreciation in schizophrenia could be attributed to impairment
      in more basic neurocognitive domains, namely, selective and sustained attention
      as well as phonological word fluency.

PMID- 17435484
TI  - Spousal bereavement in older adults: common, resilient, and chronic grief with
      defining characteristics.
AB  - The purpose of this study was to identify empirically patterns of grief among 141
      older bereaved spouses. A longitudinal hierarchical cluster procedure with the
      Ward agglomeration method was used to identify distinct clusters based on grief
      scores. Three clusters were identified: common (49%), resilient (34%), and
      chronic (17%) grief. Members of the common grief cluster experienced elevated
      levels of grief and depressive symptoms that decreased over time. Members of the
      resilient cluster experienced the lowest levels of grief and depression and the
      highest quality of life. The chronic grief cluster experienced the highest levels
      of grief and depression, more sudden deaths, the lowest self-esteem, and the
      highest marital dependency. The majority in this chronic cluster also met
      proposed criteria for a diagnosis of complicated grief. Five out of every six
      bereaved spouses adjusted well over time, and about a third of these showed
      considerable resilience without negative consequences. One out of six experienced
      a chronic grief syndrome. Early identification of this syndrome can lead to
      referral to newly emergent treatments specific for grief.

PMID- 17435485
TI  - Traumatic events and suicidal behavior: results from a national mental health
      survey.
AB  - The current study examined whether exposure to different types of traumatic
      events was differentially associated with suicidal ideation and attempts after
      adjusting for sociodemographic factors and presence of mental and physical
      disorders. Data came from the US National Comorbidity Survey Part II (N = 5877,
      aged 15-54 years, response rate: 82.4%) public use dataset. Interpersonal traumas
      and exposure to three or more types of traumatic events were particularly
      associated with suicidal behaviors. Age of onset analyses revealed that the age
      of traumatic exposure was earlier than the age at which suicidal behaviors began
      in the majority of respondents. The results imply that exposure to traumatic
      events is associated with the incidence of suicidal behaviors above and beyond
      the effect of sociodemographics, mental disorders, and physical disorders
      assessed in the survey. Clinicians and researchers need to be aware of these
      findings to determine early intervention programs.

PMID- 17435486
TI  - Convergence between the Achenbach youth self-report and structured diagnostic
      interview diagnoses in ADHD and non-ADHD youth.
AB  - We evaluated the convergence of Achenbach youth self-report (YSR) scales with
      attention-deficit hyperactivity disorder (ADHD) and psychiatric comorbidity
      derived from self-report structured interviews. Subjects were 251 youths older
      than 12 years assessed with YSR scales and directly obtained structured
      diagnostic interview. We evaluated the strength of association between each YSR
      scale and structured-interview derived diagnoses using total predictive value
      (TPV) and odds ratios (OR). Excellent convergence was found between the YSR
      attention problems with the structured interview derived diagnosis of ADHD,
      between the YSR delinquent behavior scale and the diagnosis of conduct disorder,
      and between the YSR anxiety/depression and withdrawn scales and the diagnosis of
      major depression, and between the YSR social problems and somatic scales and the
      diagnosis of anxiety. These findings indicate that the YSR could serve as a rapid
      and cost-effective diagnostic tool to identify major psychopathology in high-risk
      adolescents.

PMID- 17435487
TI  - Therapeutic alliance and improvements in work performance over time in patients
      with schizophrenia.
AB  - While therapeutic alliance (TA) in schizophrenia has been linked with treatment
      adherence and outcome, less is known about its relationship to rehabilitation
      outcome. To examine this issue, we classified persons who had been enrolled in a
      rehabilitation study as having higher or lower levels of TA based on an observer
      assessment midway through treatment and compared their work performance at weeks
      1, 11, and 23. Repeated measures analysis of variance found group effects for
      Work Quality and Personal Presentation with the higher TA group having better
      overall performance on both. Time effects were found for Work Quality and
      Personal Presentation with the sample overall showing improvement over the course
      of rehabilitation. Interactions were found for Cooperativeness and Work Quality
      with the higher TA group showing steady increases, whereas the lower TA group
      showed initial improvement followed by a decline. Results suggest that forming a
      strong TA may enhance rehabilitation among persons with schizophrenia.

PMID- 17435488
TI  - Public health in rural America.

PMID- 17435489
TI  - Undergraduate public health education: supporting the future of public health.

PMID- 17435490
TI  - The president's fiscal year 2007 initiative for human immunodeficiency virus
      counseling and testing expansion in the United States: a scenario analysis of its
      coverage, impact, and cost-effectiveness.
AB  - INTRODUCTION: When adjusted for inflation, the federal investment in human
      immunodeficiency virus (HIV) prevention in the United States has been trending
      downward for several years. However, for fiscal year 2007, President Bush has
      proposed to Congress a $93 million increase in HIV prevention efforts focused on
      HIV counseling and rapid testing in high-risk communities. OBJECTIVE: Here, we
      estimate the coverage level of an investment of $93 million for rapid testing and
      counseling services, estimate the number of HIV infections that might be expected
      to be prevented by this initiative, and calculate the cost-per-infection
      prevented. METHODS: Standard methods of scenario and cost-effectiveness analysis
      were employed, and a 1-year time horizon was used. Calculations were done
      assuming both a societal perspective and a payor perspective. RESULTS: Assuming
      full societal perspective costs, about 1.4 million clients could be reached, but
      if the payor's perspective is used (and clients are assumed to absorb the costs
      of their time spent and transportation), then coverage could expand to 2.9
      million clients. Depending on the perspective used, it is estimated that between
      13,014 and 26,984 persons living with HIV could newly learn their serostatus, and
      that between 1,223 and 2,537 HIV infections could be prevented as a function of
      the initiative. Under both societal and payor perspectives, the gross cost per
      infection averted is less than the medical care costs for one case of HIV
      disease. CONCLUSIONS: We conclude that the president's proposed $93 million
      initiative for HIV counseling and rapid testing in the United States would have
      favorable public health benefits and be cost saving to society (even if it does
      not address all unmet HIV prevention needs in the United States). However, future
      research should seek to determine whether rapid counseling and testing are the
      optimal use of a new $93 million investment in HIV prevention.

PMID- 17435491
TI  - A "Community Manifesto" for gay and bisexual men: an appeal to control HIV/STDs.
AB  - BACKGROUND: In response to increasing rates of sexually transmitted diseases
      (STDs) among men who have sex with men (MSM) in Seattle & King County, a task
      force including community members, HIV/AIDS professionals, and health department
      staff authored "A Community Manifesto: A New Response to HIV and STDs." The
      manifesto emphasized both personal and collective responsibility for gay and
      bisexual men to stop the spread of STDs. METHODS: The manifesto was published in
      local media over a 15-month period. We conducted a survey (via Web, mail-in, and
      street intercept), focus groups, and a community forum to evaluate the impact of
      the manifesto among Seattle & King County MSM. RESULTS: Most respondents
      supported the manifesto and reported that it made them think about their sexual
      behaviors; more than 25 percent reported changing sexual behavior as a result of
      the manifesto, but the document generated several controversies. CONCLUSIONS:
      Publicly declaring values associated with sexual behavior and attempting to
      establish and reinforce sexual norms within MSM communities can cause
      controversy; however, such efforts may increase awareness, dialogue, and behavior
      change at a community level and be important for increasing awareness and
      behaviors that demonstrate collective care and responsibility among MSM.

PMID- 17435492
TI  - Human immunodeficiency virus counseling, testing, and referral of close contacts
      to patients with pulmonary tuberculosis: feasibility and costs.
AB  - BACKGROUND: We aimed to increase human immunodeficiency virus (HIV) counseling,
      testing, referral (CTR), and knowledge of HIV serostatus of close contacts of
      tuberculosis patients and improve tuberculosis screening and treatment of HIV
      infected contacts. METHODS: Of close contacts to infectious tuberculosis patients
      reported from December 2002 to November 2003, investigators (1) offered HIV CTR,
      (2) identified factors associated with HIV testing, and (3) assessed study costs.
      RESULTS: Of 614 contacts, 569 (93%) were provided HIV information and offered HIV
      CTR. Of the 569, 58 (10%) were previously HIV tested; 165 (29%) were newly HIV
      tested; and 346 (61%) were not tested. None of the 165 newly HIV tested contacts
      were HIV infected. Contacts more likely to be newly HIV tested (vs not tested)
      included those aged 18-24, Hispanic, or non-Hispanic Black. Of 24 HIV-infected
      contacts, 71 percent received chest-radiograph screening for tuberculosis
      disease; 56 percent of 18 eligible for latent-tuberculosis-infection treatment
      started and half completed. It cost $1 per patient to provide HIV information and
      $5-$8 to offer HIV CTR. CONCLUSION: The project increased HIV CTR of close
      contacts of infectious tuberculosis patients. The important factor for success in
      knowing contacts' HIV serostatus was simply for TB program staff to ask about it
      and offer the test to those who did not know their status.

PMID- 17435493
TI  - Benefits and adverse effects of hepatitis C screening: early results of a
      screening program.
AB  - OBJECTIVE: Early benefits and adverse effects of hepatitis C screening among
      people who screened anti-hepatitis C virus (HCV) positive were investigated.
      METHODS: Hepatitis screening program records were abstracted to identify the
      target population and obtain information about hepatitis A and B vaccination
      (recommended vaccines if anti-HCV positive). Telephone interviews were conducted
      using a standardized questionnaire with items regarding clients' medical
      evaluation, behaviors to prevent liver damage and prevent HCV transmission, and
      adverse effects experienced. RESULTS AND CONCLUSIONS: Of 269 eligible clients,
      147 were susceptible to hepatitis A (IgG negative), and 116 (78.9%) received at
      least 1 hepatitis A vaccine dose. Of 119 clients susceptible to hepatitis B, 101
      (84.9%) received at least one dose of hepatitis B vaccine. Fifty-six (20.8%) were
      reached by phone, and 44 (78.6%) consented to the interview. All interviewed
      clients reported one or more positive behaviors to protect their liver or prevent
      HCV transmission; 51.2 percent reported at least one adverse effect related to
      knowing their positive anti-HCV status, most commonly difficulty obtaining health
      insurance; and 86.0 percent reported satisfaction with their decision to be
      tested. Results suggest that most anti-HCV-positive clients had some benefit from
      screening, and highlight the need for further studies.

PMID- 17435494
TI  - Perinatal periods of risk analysis of infant mortality in Jackson County,
      Missouri.
AB  - The perinatal periods of risk (PPOR) methodology provides an easy-to-use
      analytical approach to infant mortality that helps focus community initiatives
      for improving maternal and infant health. Because few analyses have been
      published, many public health practitioners may be unfamiliar with PPOR. This
      article demonstrates the application of PPOR analysis using infant mortality in
      Jackson County, Missouri. While the PPOR consists of two phases, this analysis
      was restricted to the initial phase of the overall process. The second phase
      builds on the initial findings and prioritizes the contributing factors of
      fetal/infant mortality so that targeted interventions can be developed. For
      Jackson County, the PPOR analysis found that racial and geographic disparities
      existed and, for very low-birth-weight infants, different interventions
      strategies may be needed on the basis of race. In addition, a mother who
      experienced a fetal or infant death was more likely to have had a medical risk
      factor, to have smoked cigarettes, to have started prenatal care after the first
      trimester or received no prenatal care, and to have been nulliparous.

PMID- 17435495
TI  - Maternity services and the role of the traditional birth attendant, bidan
      kampung, in rural Malaysia.
AB  - This study was undertaken to explore the roles played by bidan kampungs and
      understand their contribution to rural Malay women during pregnancy and
      childbirth hundred sixteen pregnant women, 13 Western midwives, and 12 bidan
      kampungs were recruited using convenience and snowball sampling. Data were
      collected from focus groups, in-depth interviews, field notes, and observations.
      The findings indicated that although the women were happy to have Western
      maternity care, they valued the social and spiritual support received from bidan
      kampungs during pregnancy and postnatal care. Western care was considered useful
      for "modern" illnesses. The traditional maternity care that women received
      included pantang or ritual prohibitions that helped them through pregnancy and
      helped them achieve better postnatal recovery. The study indicates that there is
      a need to combine Western and traditional care for the benefit of the pregnant
      women and their infants' health.

PMID- 17435496
TI  - On the road to the national objectives: a case study of Diabetes Prevention and
      Control Programs.
AB  - The purpose of this case study research was to understand common characteristics
      of high-performing Diabetes Prevention and Control Programs (DPCPs) that enable
      them to achieve national diabetes objectives within a Model of Influence. The
      case consisted of five selected DPCPs in California, Kentucky, Minnesota, New
      York, and Utah. Visits to each site facilitated data collection including
      document reviews, interviews, and observations. Data analysis involved content
      analysis, developing typologies, pattern matching, member checking, and
      triangulation. Results indicate that high-performing DPCPs share the following
      common characteristics in efforts to achieve national objectives: (1) fit the
      context, (2) assume multiple roles, (3) build relationships, (4) negotiate
      systems, (5) frame with a public health perspective, and (6) understand that
      there is "something about diabetes." Results provide insights for public health
      leadership to strengthen capacities of comparable state-based programs.

PMID- 17435497
TI  - The 2005 British Columbia Smoking Cessation Mass Media Campaign and short-term
      changes in smoking.
AB  - OBJECTIVE: The objective of this study was to evaluate the impact of the 2005
      British Columbia Ministry of Health Smoking Cessation Mass Media Campaign on
      short-term smoking behavior. METHOD: National cross-sectional data are used with
      a quasi-experimental approach to test the impact of the campaign. RESULTS AND
      DISCUSSION: Findings indicate that prevalence and average number of cigarettes
      smoked per day deviated upward from trend for the rest of Canada (P = .08; P =
      .01) but not for British Columbia. They also indicate that British Columbia
      smokers in lower risk groups reduced their average daily consumption of
      cigarettes over and above the 1999-2004 trend (-2.23; P = .10), whereas smokers
      in the rest of Canada did not, and that British Columbia smokers in high-risk
      groups did not increase their average daily consumption of cigarettes over and
      above the 1999-2004 trend, whereas smokers in the rest of Canada did (2.97; P =
      .01). CONCLUSION: The overall poorer performance of high-risk groups is
      attributed to high exposure to cigarette smoking, which reduces a smoker's
      chances of successful cessation. In particular, high-risk groups are by
      definition more likely to be exposed to smoking by peers, but are also less
      likely to work in workplaces with smoking bans, which are shown to have a
      substantial impact on prevalence. Results suggest that for mass media campaigns
      to be more effective with high-risk groups, they need to be combined with other
      incentives, and that more prolonged interventions should be considered.

PMID- 17435498
TI  - Assessing influenza vaccine utilization in physician offices serving adult
      patients: experience during a season of vaccine delays and shortages.
AB  - BACKGROUND: Influenza vaccination among US adults has plateaued at suboptimal
      levels. Severe delays and shortages of influenza vaccine prompted revised
      guidances to prioritize vaccine first to persons at greatest risk for serious
      influenza complications and to create vaccine stockpiles. OBJECTIVES: (1) Pilot
      an assessment of influenza vaccine use in a large sample of physician offices
      with adult patients. (2) Apply the method to assess vaccine receipt by age and
      risk groups. METHODS: Influenza vaccination and risk status for the 2000-2001
      season were obtained from record review conducted in November 2001 to April 2002
      for adult patients in a sample of physicians' offices in eight states.
      Participating physicians also completed a questionnaire. RESULTS: The assessment
      method was feasible to implement. One hundred eighteen physicians participated.
      They administered more than 83 percent of doses to prioritized groups in October
      and November compared with 74 percent of doses during the entire season. Office
      based vaccination coverage was less than 40 percent in all age and risk groups.
      More than 50 percent of participating physicians reported unused doses.
      CONCLUSIONS: Office-based assessments of vaccine utilization can be a valuable
      evaluation tool. Vaccine distribution was consistent with recommendations to
      target early vaccination to priority groups. Results highlight the difficulty
      distributing vaccine late in the season and the need for strategies to improve
      vaccination coverage, particularly when vaccine supply is inadequate.

PMID- 17435499
TI  - Legal preparation and pandemic influenza.

PMID- 17435500
TI  - Pandemic influenza preparedness, community engagement, and local public health
      practice.

PMID- 17435501
TI  - The power of positive personal regard.

PMID- 17435502
TI  - Symptoms in a population of contact lens and noncontact lens wearers under
      different environmental conditions.
AB  - PURPOSE: To investigate ocular symptoms related to dryness in an adult population
      of contact lens (CL) and non contact lens wearers (n-CL) using video display
      terminals (VDT) for different periods of time under different indoor conditions
      related to air conditioning (AC) and heating units (HU) exposure. METHODS: A
      questionnaire was distributed to 334 people within a university population of
      which 258 were part of the n-CL group and 76 of the CL wearers to assess symptoms
      of ocular discomfort potentially related to dryness. Only soft contact lens (SCL)
      wearers (n = 71) were included for further statistical analysis because of the
      reduced number of people wearing other lens types. A 2:1 match by gender group of
      142 subjects in the n-CL group was used as a control sample. RESULTS: There was a
      marked difference between the prevalence of symptoms and the way they are
      reported by CL and n-CL wearers. Red eye, itching, and scratchiness are more
      common among CL wearers, but the difference is statistically significant only for
      scratchiness (p < 0.01, chi(2)). The vast majority of subjects who reported
      symptoms often and at the end of the day are significantly more prevalent among
      CL wearers (p < 0.01, chi(2)). Gender differences were also encountered. Female
      CL wearers reported more scratchiness than males in the n-CL wearing group (p =
      0.029, chi(2)) and in the CL group (p < 0.008, chi(2)). Females wearing CL
      reported symptoms of red eye (p = 0.043, chi(2)) and scratchiness (p < 0.001,
      chi(2)) more significantly than those in the n-CL group. Within the CL group, the
      prevalence of symptoms occurring sometimes or often and at the end of the day was
      higher among females (p < 0.001, chi(2)). The use of VDT was associated with a
      higher level of scratchiness among CL wearers (p < 0.05, chi(2)). The number of
      hours working with VDTs seemed to be associated with an increase in the
      prevalence of burning sensation in the CL group (p < 0.01, chi(2)), whereas
      symptoms like red eye and scratchiness also increased significantly among n-CL
      wearers. Compared to n-CL wearers, all symptoms increase in CL wearers in
      environments with AC and HU, except excessive tearing. However, these differences
      are only statistically significant for scratchiness. CONCLUSIONS: Our results
      show that people who wear soft CL and work with VDTs for longer periods of time
      are more likely to develop symptoms like eye burning and scratchiness than n-CL
      wearers. This risk could be higher for women than men. Scratchiness and the
      appearance of symptoms near the end of the day are typically associated with
      ocular discomfort during CL wear in this sample, and clinicians should question
      their patients about these symptoms to anticipate serious discomfort.

PMID- 17435503
TI  - Oxygen permeability and water content of silicone hydrogel contact lens
      materials.
AB  - PURPOSE: To measure the oxygen permeability (Dk) and water content (WC) of
      silicone hydrogel (Si-Hy) contact lens materials. METHODS: Randomized and masked
      determinations of the Dk of 5 Si-Hy and two hydrogel materials were made using a
      modified version of the polarographic measurement method described in ISO 9913-1.
      Stacks of one to six parallel-sided contact lenses (all -1.00 DS) were evaluated,
      with each stack measured at least twice. The resulting value for t/Dk was plotted
      against the thickness (t) of each stack, with Dk calculated as the inverse of the
      gradient of this relationship. This methodology corrects for boundary effects. A
      mathematical calculation was used to correct for edge effects. Gravimetric
      determination of lens WC was conducted at room temperature and 35 degrees C.
      RESULTS: Measured values (+/-95% CI) of Dk, and WC at room temperature, with
      manufacturer-claimed values in parentheses, were Focus Night and Day: Dk 162.0 +/
      9.8 (140), WC 23.0 +/- 3.2 (24); Acuvue Oasys: Dk 107.4 +/- 7.4 (103), WC 36.9
      +/- 1.0 (38); O2 Optix: Dk 80.5 +/- 4.9 (110), WC 32.1 +/- 1.2 (33); PureVision:
      Dk 75.9 +/- 6.6 (91), WC 35.8 +/- 1.3 (36); Acuvue Advance: Dk 75.2 +/- 9.8 (60),
      WC 46.5 +/- 1.1 (47); 1. Day Acuvue: Dk 21.0 +/- 1.0 (21.4), WC [not measured]
      (58); and Seequence: Dk 8.2 +/- 0.7 (8.5), WC 36.6 +/- 2.7 (38). CONCLUSIONS:
      Claimed Dk values for Acuvue Oasys and the two reference hydrogel materials fell
      within the 95% confidence interval of our measured values. Our measurements of Dk
      for the other four Si-Hy lenses were not in agreement with claimed values. There
      is a general inverse relation between Dk and WC (both at 35 degrees C) for Si-Hy
      lenses. Our modified polarographic methodology can be successfully employed for
      measuring the Dk of Si-Hy materials.

PMID- 17435508
TI  - Risk of corneal inflammatory events with silicone hydrogel and low dk hydrogel
      extended contact lens wear: a meta-analysis.
AB  - PURPOSE: High Dk silicone hydrogel (SH) lenses have been shown to significantly
      decrease the risk of hypoxic complications compared to traditional low Dk
      hydrogels. However, the risks of inflammatory complications with SH compared to
      low Dk lenses are not as clear. A meta-analysis was performed to combine the
      relevant literature to evaluate the risks of corneal inflammatory events in users
      of SH and low Dk hydrogel extended wear lenses. METHODS: A systematic search was
      conducted using online databases, unpublished meeting abstracts, and retrieval of
      other cited references presented or published between 1990 and February 2006.
      Each study was evaluated for quality in terms of the research question, and these
      quality assessments were used to determine which studies should be used in
      subgroup analyses. A generalized linear mixed model framework with an underlying
      Poisson distribution for the occurrence of events was employed to combine
      information from the included studies. RESULTS: Twenty-three studies published or
      presented on either or both arms by February 2006 were selected for analysis. A
      total of 9,336 subjects and 18,537 eyes comprised the entire sample. Seven
      studies were published in the 1990s. Eighteen studies (78%) were prospective, and
      11 (48%) used randomization. The follow-up ranged from 4 to 36 months, with a
      median of 12 months. The rates of infiltrates for low Dk hydrogels and SH lenses
      were 7.7 (2.2, 26.7) and 14.4 (4.3, 48.2) per 100 eye-years, respectively. In the
      subset of five best quality studies, the unadjusted risk ratio for corneal
      inflammatory events for SH lenses compared to low Dk lenses was 2.18 (p < 0.005).
      Across studies, adjusted risk ratios ranged from 2.18 to 2.23 (p < 0.05), with
      strong confounding between material and length of wear. CONCLUSIONS: Based on
      published or presented studies between 1991 and 2006, there is approximately a
      twofold higher risk for corneal inflammatory events in users of SH lenses when
      typically worn for up to 30 days extended wear when compared with low Dk extended
      wear lenses when typically worn for 7 days extended wear. The increased risk
      cannot be definitively linked to SH lens materials because the effect of material
      on outcome is confounded by length of wear.

PMID- 17435509
TI  - The epidemiology of contact lens related infiltrates.
AB  - With estimated numbers of contact lens wearers worldwide exceeding 140 million,
      even complications with a low incidence will affect a significant number of
      individuals. Although contact lenses clearly have many advantages for wearers,
      certain risks have been associated with their use. Differences in risk for
      different types of contact lenses and wearing patterns have been demonstrated for
      both rare and common lens related complications. This review particularly focuses
      on the incidence and etiology of contact lens related corneal infection and
      inflammation. An understanding of the risks and contributory factors to these
      conditions is important for practitioners and will enable an informed choice of
      safer lens wear modalities, wear schedules, and hygiene regimes to be made.

PMID- 17435510
TI  - Pseudomonas aeruginosa infection and inflammation during contact lens wear: a
      review.
AB  - Infection and inflammation during contact lens wear is often associated with
      microbial contamination of lenses. Several different types of microbes that
      colonize lenses can lead to infection and inflammation, but the most common cause
      of infection (microbial keratitis; MK) remains the Gram-negative bacterium
      Pseudomonas aeruginosa. P. aeruginosa has a battery of cell-associated and
      extracellular virulence factors it can use to initiate and maintain infection.
      Its ability to produce proteases, to either invade or kill corneal cells, and to
      coordinate expression of virulence factors via quorum-sensing have been shown to
      be important during MK. Another important factor that contributes to the
      destruction of the cornea during MK is excessive activation of the host defense
      system. P. aeruginosa can activate several pathways of the immune system during
      MK, and activation often involves receptors on the corneal epithelial cells
      called toll-like receptors (TLRs). These TLRs recognize e.g., lipopolysaccharide
      or flagella from P. aeruginosa and activate the epithelial cells to produce
      inflammatory mediators such as cytokines and chemokines. These cytokines or
      chemokines recruit white blood cells, predominantly polymorphonuclear leukocytes,
      to the infection in order that they can phagocytose and kill the P. aeruginosa.
      However, continued recruitment and presence of these polymorphonuclear
      neutrophils and other white blood cells in the corneal tissue leads to
      destruction of corneal cells and tissue components. This can ultimately lead to
      scarring and vision loss.

PMID- 17435511
TI  - Targeting contact lens induced dryness and discomfort: what properties will make
      lenses more comfortable.
AB  - There are about 35 million contact lens wearers in North America, and about half
      of them are symptomatic of dryness and discomfort, more commonly experienced at
      the end of the lens wearing day. Most of these contact lens wearers do not suffer
      from true dry eye, which is a pervasive and ubiquitous disease or condition that
      affects many millions of people in North America. It seems fairly clear that the
      lens causes the eye to become uncomfortable or "dry," and unless it is
      effectively remedied, the patient will most likely discontinue lens wear. This
      review describes the dryness and discomfort effects of contact lenses and how
      contact lens properties with novel solutions have the potential for eliminating
      or alleviating these symptoms.

PMID- 17435512
TI  - Lipid deposition on hydrogel contact lenses: how history can help us today.
AB  - The tear film is a complex fluid that is precisely maintained and which is
      essential to the health of the ocular surface. One of the major components of the
      tear film is lipid, which is produced by the meibomian glands and serves many
      important functions on the ocular surface. It is estimated that there are more
      than 45 individual lipids within the tear film, which vary greatly in their
      structure and properties. The composition of the lipid within the tear film has
      an enormous influence on the stability of the tear film, with a subsequent impact
      on the occurrence of dry eye and the ultimate success of contact lens wear. The
      purpose of this review article is to describe the composition of the tear film
      lipids and their interaction with contact lens materials, with a particular
      emphasis on how the chemistry of novel silicone hydrogel materials has resulted
      in clinicians needing to understand the deposition of lipids onto contact lenses
      and how they may best manage this complication.

PMID- 17435513
TI  - Hydrogel lens comfort in challenging environments and the effect of refitting
      with silicone hydrogel lenses.
AB  - PURPOSE: The purpose of this analysis was to measure the proportion of soft
      contact lens wearers who wear lenses in challenging environments and to evaluate
      their resulting comfort in those conditions. A second objective was to determine
      whether refitting with silicone hydrogel lenses affects lens comfort among
      subjects who wear lenses in these environments. METHODS: Baseline data were
      collected from 496 hydrogel soft lens wearers on the frequency of use of contact
      lenses and the associated comfort in 12 challenging environments. Subjects were
      then refit into second generation silicone hydrogel lenses: senofilcon A (n =
      228), galyfilcon A (n = 132), or lotrafilcon B (n = 136). Comfort responses were
      compared for subjects who "always" or "frequently" used lenses in the queried
      environments after 2 weeks of silicone hydrogel daily lens wear. RESULTS: More
      than 80% of subjects used habitual lenses "always" or "frequently" while reading,
      sitting in an air-conditioned or heated car, using a computer and while driving
      at night. Less than 40% used lenses "always" or "frequently" while riding in an
      airplane, at high altitudes, or while napping or sleeping. The least comfortable
      environments were in dusty, polluted or smoky environments (30% comfortable), and
      the most comfortable were while reading and using a computer. After 2 weeks use
      of senofilcon A and galyfilcon A lenses, comfort in all environments improved
      significantly (Wilcoxon signed rank) except for using a computer with galyfilcon
      A. After 2 weeks with lotrafilcon B lenses, there was improved comfort while
      using lenses in all environments except driving at night, using a computer and
      sitting in an air-conditioned or heated car (p < 0.04, Wilcoxon signed rank).
      CONCLUSIONS: Daily wear contact lens wearers limit use of lenses during air
      travel or while napping. Use of daily wear silicone hydrogel lenses improved
      comfort significantly in most environments, allowing subjects to wear them in
      challenging environments.

PMID- 17435514
TI  - Solution toxicity in soft contact lens daily wear is associated with corneal
      inflammation.
AB  - PURPOSE: Contact lens-associated solution toxicity manifests as generalized, mild
      punctate epithelial fluorescein staining and usually is widely reported as
      asymptomatic, with no substantial clinical sequelae. This study examined the
      relationship between solution toxicity and corneal infiltrative events (CIEs) in
      soft contact lens daily wear. METHODS: Several nonrandomized interventional
      clinical trials conducted between May and November 2005 were analyzed
      retrospectively. Subjects wore commercially available soft contact lenses
      bilaterally, on a daily schedule, disinfected overnight using marketed lens care
      solutions for 3 months with monthly disposal. Solution toxicity was defined as
      diffuse punctate staining in at least four of five areas of the cornea after
      instillation of sodium fluorescein. First events of corneal staining or corneal
      infiltrates were used to calculate incidence (per 100 eye months). RESULTS: Toxic
      staining was detected in 77 of 609 subjects and all CIEs were mild and
      symptomatic or asymptomatic. The incidence of CIEs in eyes with a predisposition
      to toxic staining was 6.7% and in unaffected eyes was 2.3%. CIEs were 3-times
      more likely to occur in eyes that exhibited solution toxicity compared to
      unaffected eyes (odds ratio = 3.08, p = 0.008, 95% CI 1.40 to 6.76). Previous
      events of limbal redness (> or =grade 2.0) were not associated with CIEs (odds
      ratio = 1.53, p = 0.364, 95% CI 0.63 to 3.70). The rate of CIEs increased as the
      rate of toxic staining increased for specific lens type-solution combinations
      (Spearman's rho = 0.558, p = 0.025, n = 16), and peroxide-based solutions
      consistently resulted in the lowest rates of toxic staining and corneal
      inflammation. CONCLUSIONS: Eyes that experience solution toxicity are more likely
      to experience a CIE. Daily wear soft lens wearers should be routinely examined
      with sodium fluorescein soon after lenses are inserted and alternative
      solution/lens type combinations should be investigated if toxic staining is
      detected.

PMID- 17435515
TI  - Efficacy of contact lens multipurpose solutions against serratia marcescens.
AB  - PURPOSE: To compare the susceptibilities of clinical isolates of Serratia
      marcescens and the standard ISO ATCC 13880 strain to five contact lens
      multipurpose disinfection solutions (MPDSs). METHODS: Five commercially available
      MPDSs, containing either a polymeric biguanide or polyquaternium, were tested
      using ISO/CD 14729 stand-alone test for contact lens care products against four
      ocular isolates of S. marcescens and the strain ATCC 13880. An average log
      reduction in bacterial numbers at the manufacturer's minimum recommended
      disinfection time was determined and compared with the criteria for stand-alone
      disinfection products for each MPDS against each bacterial strain. RESULTS: All
      the MPDSs tested met the stand-alone criteria of 3-log reduction of viable
      bacteria against the ATCC strain of S. marcescens. However, there was more
      variability in their ability to meet disinfection criteria when tested against
      the clinical isolates. Two of the clinical isolates were significantly more
      resistant to disinfection than was the recommended ISO strain (p < or = 0.034).
      Two of the polyquaternium-1-based disinfection solutions (solutions D and E, p <
      or = 0.005) were less effective overall than the other MPDSs against S.
      marcescens. CONCLUSIONS: The importance of strain selection for the testing of
      MPDSs is indicated, and the use of a single laboratory strain may be insufficient
      to provide assurance that the disinfection solution will be effective against
      clinical isolates. Furthermore, clinical isolates of S. marcescens may show
      increased resistance to disinfection with polyquaternium.

PMID- 17435516
TI  - Measurements of solutions and contact lenses with a vapor pressure osmometer.
AB  - PURPOSE: To investigate the influence of sample volume and contact lens material
      on osmolality measurements made with a Wescor vapor pressure osmometer. METHODS:
      Accuracy: Sample volumes of 0.8, 2.0, and 10.0 microL were tested with 290, 320,
      and 1000 mmol/kg after the osmometer was calibrated with the intended sample
      volume. Influence of sample volume: Sample volumes ranging from 0.5 to 1.1 microL
      (0.1 steps) were applied with solutions of 290, 320, 500, and 1000 mmol/kg after
      the osmometer was calibrated with 0.8 microl, independent of the intended sample
      volume. Influence of contact lens material: Lens discs of 3.4 millimeters were
      trephined from the center of Lotrafilcon B, Nelfilcon A, Balafilcon A and
      Etafilcon A lenses, and equilibrated in phosphate buffered saline with 290
      mmol/kg after dehydration for 16 h. The osmometer was calibrated with 0.8 microl
      and lens discs were inserted into the small sample holder of the osmometer.
      RESULTS: There were no significant differences between the nominal and measured
      osmolalities for each sample volume and solution combination (all p > 0.05).
      Influence of sample volume: Differences of more than 0.1 microl between the
      calibration and sample volume significantly affected osmolality readings, with
      sample volumes larger than calibration volume resulting in lower readings, and
      smaller volumes resulting in higher readings. Influence of contact lens material:
      Measured osmolalities of Lotrafilcon B (358.8 +/- 45.4 mmol/kg) and Balafilcon A
      (356.7 +/- 38.7 mmol/kg) were not significantly different to each other (p =
      0.999) but were significantly higher than Etafilcon A (298.2 +/- 15.9 mmol/kg)
      and Nelfilcon A (281.2 +/- 12.2 mmol/kg, p < 0.05). There was no significant
      difference between Etafilcon A and Nelfilcon A lenses (p = 0.056). The main
      factors associated with measured osmolality were water content, sample volume and
      their interaction (r(2) = 0.716). CONCLUSION: Osmolality readings varied with
      calibration and sample volume, and with different contact lens materials.

PMID- 17435517
TI  - Oxygen demands with hybrid contact lenses.
AB  - PURPOSE: The purpose of this study was to assess the corneal response, as
      measured by corneal oxygen uptake, of keratoconic corneas to SoftPerm and
      SynergEyes hybrid contact lenses at the central cornea, 2.0 and 4.5 mm temporal
      to the central cornea, and 1 mm temporal to the limbus. METHODS: Corneal oxygen
      uptake rates were measured with a Clark-type polarographic electrode on the right
      eyes of 14 subjects and the left eye of 1 subject, all with keratoconus.
      Measurements were made at the central cornea, 2.0 and 4.5 mm temporal to the
      central cornea, and 1 mm temporal to the limbus. They were made for the open eye
      condition, as well as following 300 s of SoftPerm and SynergEyes hybrid contact
      lens wear. A one-way analysis of variance (ANOVA) was used to determine the
      effect of measurement location on oxygen uptake rates under uncovered eye
      conditions. To determine the difference among oxygen uptake rates relative to
      those of the uncovered eye at each measurement location for each hybrid lens, a
      two-way repeated measures ANOVA was used. Multiple comparisons with Tukey-Kramer
      adjustment were used post hoc to determine which locations were significantly
      different. RESULTS: For the uncovered keratoconic cornea, there was no
      significant difference among the oxygen uptake rates associated with the three
      corneal locations; however, the oxygen uptake rates measured 1 mm temporal to the
      limbus were significantly higher than those measured at the three corneal
      locations. Comparison of oxygen uptake rates measured with the SoftPerm and
      SynergEyes lenses relative to those of the uncovered eye at each location
      revealed significantly higher rates at the peripheral cornea than at the central
      cornea. At all locations, the relative oxygen uptake rates obtained with the
      SynergEyes lenses were lower than those obtained with the SoftPerm lenses.
      CONCLUSIONS: The SynergEyes lens allows significantly more oxygen to reach the
      cornea during wear than the SoftPerm lens at the central cornea, as well as 2.0
      mm and 4.5 mm temporal to the central cornea.

PMID- 17435518
TI  - Corneal refractive therapy with different lens materials, part 1: corneal,
      stromal, and epithelial thickness changes.
AB  - PURPOSE: To assess the corneal swelling response to two myopic correction corneal
      refractive therapy (CRT) lenses of varying Dk/t values, worn for a single night.
      Change in thickness of the total cornea, stroma, and epithelium was measured
      across the horizontal meridian using optical coherence tomography (OCT). METHODS:
      In this double-masked, randomized study, twenty subjects wore a CRT design lens
      in each eye, manufactured from Menicon Z (MenZ; Dk/t = 91) and Equalens II (EqII;
      Dk/t = 47) materials. Baseline corneal thickness was measured centrally and at
      four points either side of the central cornea using OCT, the night before
      sleeping at the Centre for Contact Lens Research. The next morning, lenses were
      removed, and thickness measurements were repeated 1, 3, 6, and 12 h after
      removal. RESULTS: On lens removal, the MenZ eye had central and paracentral
      corneal swelling (mean +/- SD) of 4.1 +/- 2.0% and 5.6 +/- 2.4%, and the EqII eye
      had 5.8 +/- 2.6% and 7.0 +/- 2.6%. These values were significantly different from
      baseline (ReANOVA; p < 0.001) and were different between lens materials (p <
      0.001). The central epithelium thinned by 10.0 +/- 4.5% in the MenZ eye and by
      10.2 +/- 8.5% in the EqII eye, with the mid-peripheral epithelium thickening by
      13.4 +/- 7.9% in the MenZ eye and 18.3 +/- 9.8% in the EqII eye (all changes
      different from baseline p < 0.001). These epithelial values were not
      statistically different between materials (p > 0.05). Stromal swelling values on
      lens removal were 5.7 +/- 2.2% centrally and 5.5 +/- 3.0% mid-peripherally (MenZ)
      and 7.7 +/- 3.1% centrally and 6.6 +/- 2.9% mid-peripherally (EqII) (all p <
      0.001 from baseline). Central stromal swelling was different between eyes at lens
      removal (p < 0.001). Stromal thickness in both eyes returned to baseline values
      within 3 h. CONCLUSION: The higher-Dk/t MenZ material caused significantly less
      overnight corneal and stromal swelling than the Eqll material, which reinforces
      the need to prescribe lenses with high Dk/t for overnight wear. Neither central
      epithelial thinning nor paracentral thickening are significantly affected by
      Dk/t.

PMID- 17435519
TI  - Corneal refractive therapy with different lens materials, part 2: effect of
      oxygen transmissibility on corneal shape and optical characteristics.
AB  - PURPOSE: To compare the effects of two different oxygen transmissible (Dk/t)
      lenses on corneal shape and optical performance after one night of corneal
      refractive therapy (CRT(R)) for myopia. METHODS: Twenty myopic subjects were fit
      with Menicon Z (MZ) (Dk/t = 90.6, Paragon CRT(R) lenses) on one eye and an
      Equalens II (EII) CRT lens (Dk/t = 47.2) on the contralateral eye (eye
      randomized). Corneal topography, refractive error and aberrations were measured
      before lens insertion (baseline), and the following day after overnight lens
      wear, on lens removal and 1, 3, 6, 12 h later. Root mean square wavefront errors
      were measured using 4.5 mm pupils. RESULTS: Averaged over position and time, the
      horizontal corneal curvature was statistically different between the MZ and EII
      lens-wearing eyes (p = 0.011). The central cornea flattened similarly (p = 0.886)
      and the mid-periphery steepened in both eyes (p = 0.061) from baseline. The EII
      lens-wearing eyes were steeper in the mid-periphery than the MZ eyes immediately
      after lens removal and at the 1-h visit (p < or = 0.032). Central corneal
      flattening and mid-peripheral corneal steepening regressed over time (all p <
      0.001) but did not recover to baseline by 12 h (all p < 0.004). Myopia was
      reduced equally by 0.84 +/- 0.83 D for the MZ-lens wearing eyes and 0.84 +/- 0.87
      D for the EII eyes (p = 0.969). Coma increased from baseline 1.85X (0.056 +/-
      0.081 microm) for the MZ-lens wearing eyes and 1.72X (0.048 +/- 0.084 microm) for
      the EII eyes (both p < 0.001). Spherical aberration increased from baseline 4.55X
      (0.101 +/- 0.077 microm) for the MZ-lens wearing eyes and 4.31X (0.085 +/- 0.076
      microm) for the EII eyes (both p < 0.001), but there were no differences between
      the MZ and EII eyes (all p > or = 0.308). Coma and spherical aberration did not
      return to baseline by 12 h (both p < or = 0.007). CONCLUSIONS: After one night of
      CRT lens wear, changes in corneal shape were slightly different, with more mid
      peripheral steepening in the EII eyes compared to the MZ eyes. Change in central
      corneal curvature and optical performance were similar in both eyes.

PMID- 17435520
TI  - Corneal shape and optical performance after one night of corneal refractive
      therapy for hyperopia.
AB  - PURPOSE: To investigate the corneal shape and optical performance following one
      night of Corneal Refractive Therapy for hyperopia (CRTH). METHODS: Twenty
      subjects (spherical equivalent: -2.14 +/- 2.54 D) were fit with a Paragon CRTH
      lens (Dk = 100) on one eye randomly. The other eye served as the control.
      Aberrations, refractive error, and corneal topography at various locations along
      the horizontal meridian were measured at baseline prior to lens insertion, and
      immediately after lens removal and at 1, 3, 6, 12, and 28 hours later. Root mean
      square wavefront errors were measured using a 4.5 mm pupil size. RESULTS: After
      one night of CRTH lens wear, the central cornea steepened and paracentral region
      flattened in the experimental eyes (p < 0.001), whereas no significant location
      effect was found in the control eyes (p = 0.139). Refractive error (mean +/- SE)
      changed by 1.23 +/- 0.21 D (p < 0.001). The defocus increased by 0.58 +/- 0.09
      microm (p < 0.001). Higher-order aberrations, coma, and spherical aberrations
      increased by factors of 2.69, 2.58, and 4.07, respectively (all p < 0.001).
      Spherical aberrations shifted from positive to negative. Astigmatism did not
      change over time (p = 0.771). All parameters returned to baseline by 28 hours
      (all p > or = 0.808). Aberrations and refractive error did not change in the
      control eyes (all p > or = 0.082). CONCLUSIONS.: The CRTH lens steepens the
      central cornea and flattens the paracentral region, which alters the ametropia by
      inducing a myopic shift. It appears to be effective for correcting hyperopia and
      also is reversible.

PMID- 17435521
TI  - Contact lenses: optimal vision--sub-optimal carrier?
AB  - The development of silicone hydrogel contact lenses with high oxygen
      permeabilities is a major step forward in vision correction. This advance in
      contact lenses material technology provides breakthrough levels of oxygen to the
      cornea. However, there are still important issues yet to be addressed by
      researchers, practitioners, and industry. Factors such as adequate correction for
      all refractive errors, microbial keratitis, comfort, and suitable lens care and
      lens biocompatibility are discussed from the authors' perspective.

PMID- 17435522
TI  - Temporal bone actinomycosis: a histopathologic report.

PMID- 17435523
TI  - Asymmetry in noise-induced hearing loss: relevance of acoustic reflex and left or
      right handedness.
AB  - OBJECTIVE: Noise-induced hearing loss (NIHL) is more severe in the left ear than
      the right ear. The aim of this study was to examine the possible association of
      handedness and acoustic reflex parameters on right or left NIHL predominance.
      STUDY DESIGN: Retrospective case review and prospective series. SETTING: Tertiary
      center. PATIENTS: Three samples were studied: 1) the files of 4,277 army
      personnel with NIHL were reviewed to analyze the relation between the side
      affected and age, sex, duration of noise exposure, and acoustic damage; 2) an
      additional 119 army personnel with NIHL were evaluated for the possible
      association of handedness and NIHL asymmetry; and 3) fifty-one normal-hearing
      subjects were tested for threshold and latency of acoustic reflex by handedness.
      INTERVENTION: None. MAIN OUTCOME MEASURE: Differences in NIHL asymmetry by
      background and noise-related variables and handedness. RESULTS: NIHL was more
      pronounced in the left ear, regardless of demographic characteristics, noise
      exposure parameters, acoustic reflex measures, or handedness. CONCLUSION: The
      asymmetry in hearing loss severity may be attributed to the cortical pathways,
      specifically to the more pronounced efferent auditory system on the right side,
      which reduces the susceptibility of the right ear to cochlear insult.

PMID- 17435526
TI  - Optics in research renaissance: but now making objects invisible?

PMID- 17435529
TI  - Potential higher-order aberration cues for sphero-cylindrical refractive error
      development.
AB  - PURPOSE: To investigate analytically whether higher-order wavefront errors
      comprising combinations of trefoil along 30 degrees (trefoil30), vertical coma,
      and spherical aberration could provide cues to sphero-cylindrical refractive
      error development. METHODS: A total of 25 test wavefronts, subdivided into five
      different types and five levels of higher-order root mean square errors (HO-RMS),
      were created for the study. One type contained spherical aberration only,
      producing HO-RMS levels between 0.1 and 0.5 microm. Four wavefront types
      contained coma, trefoil, and spherical aberration of various sign combinations
      also producing HO-RMS levels between 0.1 and 0.5 microm. From the 25 wavefronts,
      refractive power maps were created and 2025 different sphero-cylindrical
      combinations were added to each refractive power map. For each sphero-cylinder
      combination, the visual Strehl ratio based on the modulation transfer function
      (VSMTF) was calculated. Retinal images and refractive power histograms were
      calculated for the refractive power maps corresponding to the peak of the VSMTF.
      RESULTS: Spherical aberration affected the best focal plane thereby inducing
      spherical or defocus cues. The VSMTF produced by vertical coma and trefoil30, in
      combination with spherical aberration, could be improved with sphero-cylinders of
      various magnitudes and directions (i.e., with-the-rule, against-the rule, myopic
      astigmatism, or hyperopic astigmatism). Clinical significance of sphero-cylinders
      (i.e., >or=0.25 D) was reached at HO-RMS levels between 0.2 and 0.3 microm for a
      5-mm pupil zone. CONCLUSIONS: In the context of compensatory blur driven eye
      growth, commonly occurring combinations of the three considered higher-order
      aberrations have the potential to produce cues to eye growth resulting in myopia
      and with-the-rule astigmatism.

PMID- 17435527
TI  - The impact of a video intervention on the use of low vision assistive devices.
AB  - PURPOSE: An image-enhanced educational and motivational video was developed for
      patients with low vision and their caretakers. Impact on knowledge, self
      efficacy, and attitudes was assessed. METHODS: The video incorporated cognitive
      restructuring to change emotional response; a "virtual home"; a veridical
      simulation of vision with age-related macular degeneration and contrast
      enhancement of the video. Subjects (median age 77.5) were randomized into control
      (n=79) and intervention (n=75) groups. Telephone interviews were at baseline, 2
      weeks and 3 months. Main outcome measures were: knowledge (eight questions), self
      efficacy score (seven questions), adaptive behaviors (10 questions), willingness
      to use devices, and emotional response (4-point scales). RESULTS: The
      intervention group showed a statistically significant improvement in knowledge,
      (difference of 1.1 out of eight questions, p<0.001). Change in use of books-on
      tape was more for the intervention group than for controls (p=0.005). The
      intervention group increased use of books-on-tape from 28 to 51% whereas the
      control group did not (34% at both times). However, there was no significant
      change in the use of other assistive devices, including magnifiers. Both groups
      increased adaptive behaviors. There was no significant difference in change of
      self-efficacy score or in emotional affect between the two groups. CONCLUSIONS:
      The video had a small, but statistically significant impact on knowledge and
      willingness to use assistive devices. There was little impact on adaptive
      behaviors and emotional affect. The minimal changes in outcome were
      disappointing, but this does not minimize the importance of patient education; it
      just emphasizes how hard it is to effect change.

PMID- 17435530
TI  - Refractive errors of medical students in Turkey: one year follow-up of refraction
      and biometry.
AB  - PURPOSE: This study was conducted to determine the prevalence of refractive
      errors in Turkish medical students as well as to determine the change in
      refractive status of medical students within 1 year. Besides general refractive
      characteristics of the students, the possible relationship between the occurrence
      of myopia and several factors was also determined. METHODS: Two hundred and seven
      medical students (114 female/93 male) were checked for their refractive status as
      determined by cycloplegic autorefraction. In addition to keratometric and
      biometric measurements students also answered a detailed questionnaire. One year
      later, medical students who participated to the study were re-examined. RESULTS:
      Myopia occurred in 32.9% of medical students with low myopia (spherical
      equivalent between -0.75 diopters [D] and -2.99 D) being the most common type
      (81%). The frequency of myopia was not significantly different between female and
      male medical students (37.7 and 26.8%, respectively; p=0.13). Adult onset myopia
      (onset at age 18 years or older) comprised 14.7% of all myopia cases. Myopic
      students were significantly more likely to report parental myopia. The percentage
      of myopes and nonmyopes reporting having one or two myopic parents was 51.5 and
      28.8%, respectively (p=0.002). Parental myopia was also an independent risk
      factor associated with the occurrence of myopia on multivariate analysis (odds
      ratio [OR]=3.69, 95% confidence interval [CI]=1.98-6.87). Nonmyopes also reported
      a significantly higher prevalence of outdoor activity before and at age seven
      (68.4%) than did myopes (48.6%), (p=0.009). Outdoor activity during early
      childhood was found to be protective for myopia on multivariate analysis
      (OR=0.44, %95 CI=0.23-0.82). There was no significant difference between myopes
      and nonmyopes with respect to amount of close-up activity. No significant shift
      of refraction occurred within 1 year. CONCLUSIONS: About one-third of Turkish
      medical students had myopia. Parental myopia was more common among myopic
      students and was a risk factor for the occurrence of myopia suggesting a familial
      predisposition. Outdoor activity in early childhood has had a protective role
      against the development of myopia in this study sample.

PMID- 17435531
TI  - Impact of confidence number on the screening accuracy of the retinomax
      autorefractor.
AB  - PURPOSE: To assess the impact of Retinomax reading confidence number on screening
      accuracy and to determine whether repeated testing to achieve a higher confidence
      number improves screening accuracy in preschool children. METHODS: Lay and nurse
      screeners trained in the use of the Retinomax Autorefractor screened 1452
      children enrolled in the Vision in Preschoolers (VIP) Phase II Study. All
      children also received a comprehensive eye examination. Using statistical
      comparison of correlated proportions, we compared sensitivity and specificity for
      detecting any VIP-targeted condition and conditions grouped by severity and by
      type (amblyopia, strabismus, significant refractive error, and unexplained
      decreased visual acuity) among three groups of children who had confidence
      numbers below, at or above the manufacturer's suggested confidence number of 8.
      The reading with the highest confidence number for each eye was used in the
      analysis. Each child's confidence number group was defined based on the lower
      confidence number of the pair of readings for the two eyes. Among the 771 (53.1%)
      children who had repeated testing either by lay or nurse screeners because of a
      low confidence number (<8) for one or both eyes in the initial testing, the same
      analyses were also conducted to compare results between the initial reading with
      confidence number<8 and repeated test reading with the highest confidence number
      in the same child. These analyses were based on the failure criteria associated
      with 90% specificity for detecting any VIP condition in VIP Phase II. We also
      examined the association between ocular conditions and confidence number.
      Hochberg procedure was used to adjust the p value for multiple comparisons.
      RESULTS: A lower confidence number category was associated with higher
      sensitivity (0.78, 0.65, and 0.61 for<8, 8, >8, respectively, p=0.04) but much
      lower specificity (0.64, 0.89, and 0.93, p<0.0001) of detecting any VIP-targeted
      condition. Through repeated testing, 87% of readings that initially had a
      confidence number below 8 reached 8 or above, and the increased confidence number
      that resulted from repeated testing was associated with significantly higher
      specificity (0.81 vs. 0.86, p=0.002) and a nonsignificant change (by -0.04 to
      0.03) in sensitivities. Children with any VIP-targeted condition, significant
      refractive error, hyperopia, astigmatism, or myopia were more likely to have a
      low confidence number. CONCLUSIONS: A higher confidence number obtained during
      Retinomax Autorefractor screening is associated with better screening accuracy.
      Repeated testing to reach the manufacturer's recommended minimum value is
      worthwhile in preschool vision screening with the Retinomax. Failure to achieve
      manufacturer's recommended minimum value through repeated testing should be a
      factor considered in referring children for a comprehensive eye examination.

PMID- 17435532
TI  - Laser scanning confocal ophthalmoscopy and polarimetry of human immunodeficiency
      virus patients without retinopathy, under antiretroviral therapy.
AB  - PURPOSE: Confocal laser scanning ophthalmoscopy (HRT; Heidelberg retinal
      tomograph II) and scanning laser polarimetry (GDx-variable corneal compensator
      [VCC]) were used to investigate whether early indicators of retinal nerve fiber
      layer (RNFL) thickness loss could be observed in patients infected with the human
      immunodeficiency virus (HIV) that had no associated retinopathy or optic
      neuropathy and were concomitantly receiving antiretroviral medications. METHODS:
      HRT and GDx-VCC parameters obtained from a group of 13 HIV-positive subjects
      (n=26 eyes) on antiretroviral therapy examined with HRT, with a subgroup of six
      subjects (n=12 eyes) examined with both HRT and GDx-VCC, were compared with those
      of a matched HIV-negative control cohort (13 subjects, n=26 eyes) examined with
      HRT, with a subgroup of five subjects (n=10 eyes) examined with both HRT and GDx
      VCC. We employed generalized estimating equations for statistical analysis.
      RESULTS: Reduced mean values for the HRT height variation contour (p<0.045) and
      HRT mean RNFL thickness (p<0.023) were observed in HIV-positive subjects
      controlling for age, sex, and race. A significantly reduced mean value
      corresponding to the GDx-VCC superior maximum (p<0.014) and inferior maximum
      (p<0.016) were also observed for the HIV-positive cohort analyzed controlling for
      age, sex, and race. CONCLUSION: HRT and GDx-VCC indicators of RNFL thickness
      appear to be significantly reduced in HIV-positive subjects without retinopathy
      or optic nerve disease using antiretroviral medication, suggesting RNFL loss
      occurs in this population of HIV-positive patients. The lack of correlation
      between CD4 counts, viral load, number of antiretroviral medications used, or
      years from diagnosis of HIV and RNFL thinning, suggests that possibly other
      factors associated with HIV infection may contribute to the apparent RNFL
      thickness loss.

PMID- 17435533
TI  - The relation between physical properties of the anterior eye and ocular surface
      temperature.
AB  - PURPOSE: To examine the relation between ocular surface temperature (OST)
      assessed by dynamic thermal imaging and physical parameters of the anterior eye
      in normal subjects. METHODS: Dynamic ocular thermography (ThermoTracer 7102MX)
      was used to record body temperature and continuous ocular surface temperature for
      8 s after a blink in the right eyes of 25 subjects. Corneal thickness, corneal
      curvature, and anterior chamber depth (ACD) were assessed using Orbscan II;
      noninvasive tear break-up time (NIBUT) was assessed using the tearscope; slit
      lamp photography was used to record tear meniscus height (TMH) and objective
      bulbar redness. RESULTS: Initial OST after a blink was significantly correlated
      only with body temperature (r=0.80, p<0.0005), NIBUT (r=-0.68, p<0.005) and
      corneal curvature (r=-0.40, p=0.05). A regression model containing all the
      variables accounted for 70% (p=0.002) of the variance in OST, of which NIBUT
      (29%, p=0.004), and body temperature (18%, p=0.005) contributed significantly.
      CONCLUSIONS: The results support previous theoretical models that OST radiation
      is principally related to the tear film; and demonstrate that it is less related
      to other characteristics such as corneal thickness, corneal curvature, and
      anterior chamber depth.

PMID- 17435534
TI  - Variable responses of Acanthamoeba strains to three multipurpose lens cleaning
      solutions.
AB  - PURPOSE: A novel method has been developed to compare Acanthamoeba strain
      differences by testing their susceptibility to multipurpose contact lens cleaning
      solutions (MPS). METHODS: This method uses surface-attached amoebae that mimic
      cells attached to a contact lens. In brief, acanthamoebae were grown on non
      nutrient agar plates with Escherichia coli prey. Blocks of agar with cysts or
      trophozoites (approximately 50 cells) were cut out and transferred to MPS [ReNu
      MultiPlus; (Bausch & Lomb, Rochester, NY), Complete (Allergan, Irvine, CA), and
      Opti-Free Express (Alcon, Ft. Worth, TX)] for up to 24 h treatment. After
      neutralizing in Dey Engley broth (Difco), blocks were washed in amoeba saline and
      reinoculated onto fresh prey bacteria. Positive growth was indicative of
      survival. RESULTS: Testing showed that the efficacy of the three MPS was
      different. Opti-Free was the most effective against cysts, followed by ReNu while
      Complete was relatively ineffective. Not surprisingly, trophozoites were more
      susceptible than cysts. CONCLUSIONS: Findings for individual MPS complement
      previous work with other methods. This study has also identified that
      environmental strains vary in their sensitivity to disinfecting solutions.
      Overall, Acanthamoeba genotypes T3, T5, and T11 from the environment were more
      resistant than the T4 isolates from the cornea and beach. This resilience
      supports previous work on temperature tolerance, in which T3 and T5, and T11
      acanthamoebae grew in temperatures up to 41 degrees C. Investigators should
      therefore consider the strain genotype and its source before embarking on MPS
      sensitivity testing.

PMID- 17435535
TI  - An evaluation of the M&S technologies smart system II for visual acuity
      measurement in young visually-normal adults.
AB  - PURPOSE: To compare visual acuity measures obtained with the M&S Technologies
      Smart System II (SSII) and the revised Early Treatment of Diabetic Retinopathy
      Study (ETDRS) charts in terms of accuracy and test-retest repeatability. METHODS:
      Monocular visual acuities were taken in 57 young, visually normal adults on two
      separate visits in which both the SSII system and the ETDRS charts were tested in
      random order by two masked examiners. The eye to be tested throughout was chosen
      randomly at the initial visit. Measurements were made through an optimal
      phoropter correction, determined by a noncycloplegic refraction for a 10-foot
      distance. Both charts were presented at 10 feet, and were matched closely for
      luminance. RESULTS: The mean visual acuity in the group was -0.16 log minimum
      angle of resolution (MAR) for the ETDRS chart and -0.18 log MAR for the SSII, a
      small but statistically significant difference. A 95% confidence interval for the
      mean difference in visual acuity between the two charts was -0.033 log MAR to 
      0.003 log MAR. The test-retest repeatability was not significantly different in
      the two tests. The 95% limits of agreement for test-retest repeatability were 
      0.13 log MAR to +0.17 log MAR for the SSII and -0.12 log MAR to +0.13 log MAR for
      the ETDRS charts. CONCLUSIONS: The SSII can provide an accurate (mean
      difference<0.033 log MAR) and repeatable alternative to the ETDRS charts for
      visual acuity measurement in young, visually normal, well-corrected individuals.

PMID- 17435536
TI  - Near point of convergence norms measured in elementary school children.
AB  - PURPOSE: Convergence insufficiency (CI) is the most prevalent of binocular
      dysfunctions. A prime finding in the diagnosis of CI is the near point of
      convergence (NPC). METHODS: The NPC was measured six different times on the same
      539 children, once in the fall and once in the spring, over the course of 3
      years. At each evaluation, the NPC was performed three consecutive times. An
      accommodative target was used in the testing and the breaks and recoveries were
      carefully measured and recorded to the nearest centimeter. Normative data for the
      break and recovery finding were calculated. RESULTS: We found that the NPC
      measures receded significantly over three consecutive tests. The recession was
      not considered clinically significant for either the break or recovery measures.
      When various break and recovery findings were compared with reported symptoms, it
      was discovered that one of the break findings statistically predicted the
      symptomatic group from the asymptomatic group. CONCLUSIONS: The NPC break and
      recovery does not change appreciably with multiple administrations of the test in
      the same test period. The criteria for a NPC break score to differentiate the
      more symptomatic and less symptomatic, elementary school children on the average
      should be 5 cm, or less. The NPC break and recovery criteria described here
      should be tentatively used as one of the benchmarks in the diagnosis of
      convergence insufficiency.

PMID- 17435537
TI  - L/M speed-matching ratio predicts reading in children.
AB  - PURPOSE: Many behavioral studies have found impaired perception of dynamic visual
      stimuli in dyslexia and several neuroimaging studies have found reduced
      activation of the human motion area MT+ in dyslexia. These results are often
      interpreted as a magnocellular (MC) deficit in dyslexia. It has also been claimed
      that colored filters can help dyslexics to read. One defining feature of the MC
      pathway is a greater weight for L-cone input than M-cone input, and at most very
      weak S-cone input. We measured the subjective speed matches between L-, M-, and S
      cone isolating stimuli in good and poor readers. METHODS: Subjects performed a
      speed-matching task with drifting cone-isolating stimuli to find the point of
      subjective equality between two drifting patterns. Such a task is known to
      activate cortical area MT+, presumably via the MC-pathway. RESULTS: L- to M-cone
      speed-match ratios were negatively correlated with single-word (r=-0.46) and
      irregular-word reading (r=-0.56) but not with non-word reading. CONCLUSIONS:
      Results suggest that relative L-cone sensitivity within the MC-pathway may limit
      orthographic reading performance.

PMID- 17435538
TI  - Surgery of residual disease following molecular-targeted therapy with imatinib
      mesylate in advanced/metastatic GIST.
AB  - OBJECTIVE: To explore the role of surgery of residual disease following a period
      of therapy with imatinib mesylate in advanced gastrointestinal stromal tumors
      (GIST). METHODS: From January 2001 to June 2005, 159 patients with
      advanced/metastatic GIST were treated with imatinib mesylate at a single
      institution. As of June 2002, 38 patients were selected for surgery following a
      variable period of imatinib therapy. Twenty-seven patients were operated on while
      they were in response, 8 in progression, 3 for localized disease. Clinical,
      pathologic, and molecular features were assessed and are reported. RESULTS:
      Postsurgery PFS was 96% at 12 months and 69% at 24 months for responding
      patients, while it was nil at 12 months for progressing ones. Disease-specific
      survival at 12 months was 100% for responding patients and 60% for progressing
      ones. In responding cases, secondary progression was mainly related to
      postsurgical imatinib discontinuation, irrespective of pathologic or molecular
      variables. In progressing patients, secondary resistance was mainly related to
      acquired mutations. CONCLUSION: In advanced GIST patients who are responding to
      imatinib mesylate, the role of surgery is not formally demonstrated at the
      moment, but this option may well be considered investigational, or suitable for
      an individualized decision-making in the lack of evidence. In our series,
      patients progressing on imatinib mesylate did not seem to have any major benefit
      from surgery, although their number is low.

PMID- 17435539
TI  - Results of tyrosine kinase inhibitor therapy followed by surgical resection for
      metastatic gastrointestinal stromal tumor.
AB  - INTRODUCTION: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of
      the intestinal tract. Nearly all tumors have an activating mutation in the KIT
      or, less often, PDGFRalpha, gene. Therapy with tyrosine kinase inhibitors
      benefits over 80% of patients with advanced GIST, but most patients eventually
      develop drug resistance. METHODS: Forty patients with metastatic GIST were
      treated with tyrosine kinase inhibitors and then underwent surgical resection.
      Based on the growth of their tumors by serial radiologic imaging, patients were
      categorized at the time of operation as having responsive disease, focal
      resistance (1 tumor growing), or multifocal resistance (more than 1 tumor
      growing). Patients were followed for a median of 15 months (range, 6-46 months)
      after surgery. RESULTS: Initially, molecular therapy achieved stable disease or a
      partial response in all but 1 patient. Surgery was performed after a median of 15
      months, and there were no perioperative deaths. After operation, the 20 patients
      with responsive disease had a 2-year progression-free survival of 61% and 2-year
      overall survival of 100%. In contrast, the 13 patients with focal resistance
      progressed after surgery at a median of 12 months and the 2-year overall survival
      was 36%. There were 7 patients with multifocal resistance and they progressed
      postoperatively at a median of 3 months and had a 1-year overall survival of 36%.
      CONCLUSION: Selected patients with metastatic GIST who have responsive disease or
      focal resistance to tyrosine kinase inhibitor therapy may benefit from elective
      surgical resection. Surgery for patients with metastatic GIST who have multifocal
      resistance is generally not indicated, and these patients should be considered
      for clinical trials of new systemic agents.

PMID- 17435540
TI  - Effective neoadjuvant therapy prior to metastasectomy: a new paradigm.

PMID- 17435541
TI  - Alvimopan, for postoperative ileus following bowel resection: a pooled analysis
      of phase III studies.
AB  - OBJECTIVE: To obtain further analysis regarding specific outcomes and alvimopan
      doses in bowel resection (BR) patients. SUMMARY BACKGROUND DATA: Although
      postoperative ileus (POI) is common after BR, there is currently no recognized
      treatment or prevention available. Alvimopan, a novel, peripherally active mu
      opioid receptor antagonist, accelerated GI recovery after BR or hysterectomy in 3
      phase III trials. METHODS: A pooled retrospective subset analysis of BR patients
      in alvimopan phase III trials was performed. Randomized BR patients received
      alvimopan 6 mg (n = 397), 12 mg (n = 413), or placebo (n = 402) >or=2 hours
      before surgery and twice daily until hospital discharge for <or=7 days. The
      primary endpoint of each trial was time to recovery of GI function. Hospital
      discharge order (DCO) written, readmission, and morbidities were also assessed.
      Cox proportional hazard models were used to analyze treatment effects on time-to
      event endpoints. RESULTS: Alvimopan (6 or 12 mg) significantly accelerated GI
      recovery (GI-3; hazard ratio = 1.28 and 1.38, respectively; P <or= 0.001 for
      both). Alvimopan significantly accelerated time to DCO written by 16 hours for 6
      mg and 18 hours for 12 mg (P < 0.001 for both) from a mean of 147 hours for
      placebo. Alvimopan-treated patients had reduced postoperative morbidity compared
      with placebo, and incidence of prolonged hospital stay or readmission was
      significantly reduced (P < 0.001). Tolerability profiles were similar among
      groups. CONCLUSIONS: Alvimopan significantly accelerated GI recovery in BR
      patients. A 12-mg dose provided more consistent benefits across both sexes and
      all ages. Postoperative morbidity rates, prolonged hospital stay, and rates of
      hospital readmission were significantly reduced. Alvimopan reduces the
      consequences of POI after BR.

PMID- 17435542
TI  - Pharmacologic management of postoperative ileus: the next chapter in GI surgery.

PMID- 17435543
TI  - Staging systems for papillary thyroid carcinoma: a review and comparison.
AB  - OBJECTIVE: To find out the most predictive staging system for papillary thyroid
      carcinoma (PTC) currently available in the literature. BACKGROUND: Various
      staging systems or risk group stratifications have been used extensively in the
      clinical management of patients with PTC, but the most predictive system for
      cancer-specific survival (CSS) based on distinct histologic types remains
      unclear. METHODS: Through a comprehensive MEDLINE search from 1965 to 2005, a
      total of 17 staging systems were found in the literature and 14 systems were
      applied to the 589 PTC patients managed at our institution from 1961 to 2001. CSS
      were calculated by Kaplan-Meier method and were compared by log-rank test. Using
      Cox proportional hazards analysis, the relative importance of each staging system
      in determining CSS was calculated by the proportion of variation (PVE). RESULTS:
      All 14 staging systems significantly predicted CSS (P < 0.001). The 3 highest
      ranked staging systems by PVE were the Metastases, Age, Completeness of
      Resection, Invasion, Size (MACIS) (18.7) followed by the new AJCC/UICC 6th
      edition tumor, node, metastases (TNM) (17.9), and the European Organization for
      Research and Treatment of Cancer (EORTC) (16.6). CONCLUSIONS: All of the
      currently available staging systems predicted CSS well in patients with PTC
      regardless of which histologic type from which they were derived. When
      predictability was measured by PVE, the MACIS system was the most predictive
      staging system and so should be the staging system of choice for PTC in the
      future.

PMID- 17435544
TI  - Trocar-less instrumentation for laparoscopy: magnetic positioning of intra
      abdominal camera and retractor.
AB  - OBJECTIVE: To develop a novel laparoscopic system of moveable instruments that
      are positioned intra-abdominally and "locked" into place by external permanent
      magnets placed on the abdomen. SUMMARY BACKGROUND DATA: In conventional
      laparoscopy, multiple trocars are required because of the limited degrees of
      freedom of conventional instrumentation, and the limited working envelope (an
      inverted cone) created by the fulcrum motion around each port. While robotic
      systems can improve the number of degrees of freedom, they are restricted by even
      smaller working envelopes. METHODS: A collaborative research group from the
      Department of Urology and the Automation & Robotics Research Institute of the
      University of Texas, Arlington built a prototype system of magnetically anchored
      instruments for trocar-less laparoscopy. The only design mandate was that the
      developed technology be able to pass into the abdomen through one existing 12-mm
      diameter trocar. RESULTS: A transabdominal "magnetic anchoring and guidance
      system" (MAGS) platform was developed to incorporate instruments, retractors, and
      a controllable intra-abdominal camera. In vitro, the platform was able to anchor
      375 and 147 g across porcine tissue 1.8 and 2.5 cm thick, respectively. The
      permanent magnet platforms were sufficiently strong to retract the porcine liver
      and securely anchor the camera. Its versatility was demonstrated by moving the
      camera to virtually any location in the peritoneum with no working envelope
      restrictions and the subsequent completion of porcine laparoscopic procedures
      with 2 trocars only. CONCLUSIONS: Trocar-less laparoscopy using magnetically
      anchored instruments is feasible and may expand intracorporeal instrument
      manipulation substantially beyond current-day capability. The ability to reduce
      the number of trocars necessary for laparoscopic surgery has the potential to
      revolutionize surgical practice.

PMID- 17435545
TI  - Mental training in surgical education: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the impact of a cognitive training method on the
      performance of simulated laparoscopic cholecystectomy in laparoscopic training
      courses. SUMMARY BACKGROUND DATA: Surgeons are like professional sportsmen in
      that they have to be able to perform complicated, fine-motor movements under
      stressful conditions. Mental training, systematically and repeatedly imagining a
      movement's performance, is a well-established technique in sports science, and
      this study aimed to determine its value in training surgeons. METHODS: A total of
      98 surgeons undergoing basic laparoscopic training participated in a randomized
      controlled trial; 31 received additional mental training, 32 additional practical
      training, and 35 received no additional training (control group). All used a
      Pelvi-Trainer simulator to perform laparoscopic cholecystectomy at baseline and
      follow-up, after any additional intervention. We used a modified Objective
      Structured Assessment of Technical Skills (OSATS) instrument to assess
      performance. Principle outcome variables were the OSATS task-specific checklist
      (11 procedural steps, scored as correctly [1] or wrongly [0] performed) and the
      global rating scale (an overall performance evaluation, scored 1-5). RESULTS:
      Improvement in the task-specific checklist score between baseline and follow-up
      differed significantly between groups (P = 0.046 on ANOVA). Least significant
      difference tests yielded differences between the mental and practical training
      groups (P = 0.024) and between the mental training and control groups (P =
      0.040), but not between the practical training and control groups (P = 0.789).
      Paired Student t test showed that performance at follow-up was significantly
      better in the mental training and control groups (mental training group, P =
      0.001; control group, P = 0.018) but not the practical training group (P =
      0.342). There were no significant intergroup differences in global rating scale
      results. CONCLUSION: Additional mental training is an effective way of optimizing
      the outcomes of further training for laparoscopic cholecystectomy. It is
      associated with fewer costs and with better outcomes in some crucial assessment
      scales than additional practical training.

PMID- 17435546
TI  - Prophylactic antibiotics for mesh inguinal hernioplasty: a meta-analysis.
AB  - OBJECTIVE: To assess the effectiveness of antibiotic prophylaxis in mesh
      hernioplasty. BACKGROUND: Antibiotic prophylaxis use in mesh inguinal
      hernioplasty is controversial. Available evidence is nonconclusive because of the
      low number of clinical trials assessing its effectiveness. Some trials have a
      small sample size that could overestimate or underestimate the real effectiveness
      of this intervention. Meta-analysis is a good method to improve these
      methodological flaws. METHODS: Meta-analysis intended to measure the benefits of
      antibiotic prophylaxis on surgical site infection rate in adult patients
      scheduled for mesh inguinal hernioplasty. Six randomized clinical trials were
      found. Quality was assessed using Cochrane Collaboration criteria. RESULTS: A
      total of 2507 patients were analyzed. Surgical site infection frequency was 1.38%
      in the antibiotic group versus 2.89% in the control group (odds ratio = 0.48; 95%
      confidence interval, 0.27-0.85). There was no statistical heterogeneity.
      Sensitivity analysis by quality did not show differences in overall results.
      CONCLUSION: Antibiotic prophylaxis use in patients submitted to mesh inguinal
      hernioplasty decreased the rate of surgical site infection by almost 50%.

PMID- 17435547
TI  - Enteral vancomycin controls methicillin-resistant Staphylococcus aureus
      endemicity in an intensive care burn unit: a 9-year prospective study.
AB  - OBJECTIVE: The aim of this study was to assess the efficacy and safety of enteral
      vancomycin in controlling MRSA endemicity in an intensive care burn unit. SUMMARY
      BACKGROUND DATA: MRSA is a serious clinical and epidemiologic problem. It is not
      uncommon that the traditional maneuvers, detection and isolation of carriers,
      fail to control endemicity due to MRSA. METHODS: All patients admitted to an
      Intensive Care Burn unit from January 1995 to February 2004 have been included in
      this prospective cohort study comprised 2 different periods. During period 1
      (January 1995 to January 2000), barrier and isolation measures were enforced.
      During period 2 (February 2000 to February 2004), patients received enteral
      vancomycin 4 times daily in addition to selective digestive decontamination.
      RESULTS: A total of 777 patients were enrolled into the study: 402 in period 1,
      and 375 in period 2. There were no significant differences in the characteristics
      of patients between the 2 periods, except for the total body surface burned area,
      30.3% in period 1 and 25.61% in period 2 (P = 0.009). There was a significant
      reduction in the incidence of patients who acquired MRSA from 115 in period 1 to
      25 in period 2 (RR, 0.22; 95% confidence interval [CI], 0.15-0.34). Similar
      reductions were observed in the number of patients with wound (RR, 0.20; 95% CI,
      0.12-0.32), blood (RR, 0.13; 95% CI, 0.04-0.35), and tracheal aspirate (RR, 0.07;
      95% CI, 0.03-0.19), samples positive for MRSA. There was no emergence of either
      vancomycin-resistant enterococci or Staphylococcus aureus with intermediate
      sensitivity to glycopeptides in period 2. CONCLUSIONS: Enteral vancomycin is an
      effective and safe method to control MRSA in intensive care burn units without
      VRE.

PMID- 17435548
TI  - Substance P regulates migration in rat intestinal epithelial cells.
AB  - OBJECTIVE: The current study examined the effect of substance P (SP) upon
      intestinal epithelial cells and the mechanistic details of this interaction.
      SUMMARY BACKGROUND DATA: Intestinal epithelial cells must be capable of migration
      to reseal mucosal wounds for several vital intestinal functions. This process is
      incompletely understood; however, recent evidence implicates the neurotransmitter
      SP in this process. METHODS: Normal rat intestinal epithelial cells (IEC-6 cells)
      were studied to identify the presence of the SP receptor (NK-1 subtype) and then
      exposed to physiologic doses of SP and antagonists to assess for increased
      migration. RESULTS: Examination IEC-6 cells revealed the presence of the SP
      receptor. Wounding of these cells followed by subsequent exposure to SP (10
      mol/L) resulted in increased migration. Similarly, SP-induced increases in
      intracellular calcium concentration and actomyosin stress fiber formation. These
      effects were all blocked through specific NK-1 receptor antagonists. CONCLUSIONS:
      These results indicate that SP stimulates intestinal epithelial migration and
      increases in calcium concentration. These data support a beneficial role for SP
      in the maintenance of intestinal mucosal homeostasis.

PMID- 17435549
TI  - Bile salts induce resistance to apoptosis through NF-kappaB-mediated XIAP
      expression.
AB  - Apoptosis plays a critical role in intestinal mucosal homeostasis. We previously
      showed that the bile salt taurodeoxycholate has a beneficial effect on the
      intestinal mucosa through an increase in resistance to apoptosis mediated by
      nuclear factor (NF)-kappaB. The current study further characterizes the effect of
      bile salts on intestinal epithelial cell susceptibility to apoptosis and
      determines if the X-linked inhibitor of apoptosis protein (XIAP) regulates bile
      salt-induced resistance to apoptosis. Exposure of normal intestinal epithelial
      cells (IEC-6) to the conjugated bile salts taurodeoxycholate (TDCA) and
      taurochenodeoxycholate (TCDCA) resulted in an increase in resistance to tumor
      necrosis factor (TNF)-alpha and cycloheximide (CHX)-induced apoptosis, and NF
      kappaB activation. Treatment with TDCA and TCDCA resulted in an increase in XIAP
      expression. Specific inhibition of NF-kappaB by infection with an adenoviral
      vector that expresses the IkappaBalpha super-repressor (IkappaBSR) prevented the
      induction of XIAP expression and the bile salt-mediated resistance to apoptosis.
      Treatment with the specific XIAP inhibitor Smac also overcame this increase in
      enterocyte resistance to apoptosis. Bile salts inhibited formation of the active
      caspase-3 from its precursor procaspase-3. Smac prevented the inhibitory effect
      of bile salts on caspase-3 activation. These results indicate that bile salts
      increase intestinal epithelial cell resistance to apoptosis through NF-kappaB
      mediated XIAP expression. Bile salt-induced XIAP mediates resistance to TNF
      alpha/CHX-induced apoptosis, at least partially, through inhibition of caspase-3
      activity. These data support an important beneficial role of bile salts in
      regulation of mucosal integrity. Decreased enterocyte exposure to luminal bile
      salts, as occurs during starvation and parenteral nutrition, may have a
      detrimental effect on mucosal integrity.

PMID- 17435550
TI  - Impact of hospital volume on recurrence and survival after surgery for gastric
      cancer.
AB  - BACKGROUND: Some, but not all, studies using registry data have suggested a small
      but significant long-term survival advantage following a curative surgical
      resection of gastric cancer at hospitals where the volume of such surgeries is
      high. However, because such data may be significantly influenced by the impact of
      postoperative mortality, and may be imbalanced for factors important to survival,
      the true nature of this relationship remains uncertain. METHODS: We conducted a
      nested volume-outcome study in a sample of 448 surgical survivors with stage IB
      through IV (M0) gastric and gastroesophageal junction adenocarcinoma, previously
      randomized to adjuvant chemoradiation after surgery or surgery alone, to measure
      the effect of hospital surgical volume, as assessed by Medicare claims data, on
      overall survival and gastric cancer recurrence. RESULTS: In this selected sample
      of postoperative survivors, hospital surgical volume was not predictive of
      overall survival (P = 0.46) or disease-free survival (P = 0.43) at a median
      follow-up of 8.9 years. However, patients who underwent either a D1 or D2
      dissection at a high- or moderate-volume center experienced an adjusted hazard
      ratio of 0.80 (95% CI, 0.53-1.20) for overall survival and 0.78 (95% CI, 0.53
      1.14) for disease-free survival compared with those patients resected at a low
      volume hospital; these results were not statistically significant. When a D0
      resection was performed, hospital procedure volume showed no impact on survival.
      CONCLUSIONS: Excluding the impact of perioperative mortality by utilizing
      prospectively recorded data from a large postoperative adjuvant trial, hospital
      procedure volume had no overall effect on long-term gastric cancer survival. The
      potential benefit of moderate- to high-volume centers for patients who underwent
      a D1 or D2 dissection requires confirmation in larger studies.

PMID- 17435551
TI  - Preoperative assessment of hepatocellular carcinoma tumor grade using needle
      biopsy: implications for transplant eligibility.
AB  - OBJECTIVE: To examine the diagnostic agreement of preoperative needle core biopsy
      (NCB) grading of hepatocellular carcinoma (HCC) compared with the final surgical
      pathologic tumor grade. SUMMARY BACKGROUND DATA: Some centers have adopted
      protocols for selecting patients with HCC for transplantation based on tumor
      grade as determined by preoperative NCB. The validity of NCB to predict final
      tumor grade has not been previously assessed. METHODS: A total of 211 patients
      who underwent hepatic resection, open radiofrequency, or transplantation for HCC
      between 1998 and 2004 were identified. Clinicopathologic, NCB, and surgical data
      were collected and analyzed using chi and kappa statistics. RESULTS: A total of
      120 (67.4%) of the 178 who underwent resection or transplantation had an NCB. On
      preoperative NCB, the majority of HCC cases were classified as well
      differentiated (n = 35; 37.6%) or moderately differentiated (n = 44; 47.3%),
      while 14 (15.1%) cases were categorized as poorly differentiated. In contrast,
      when tumor grading was based on the final surgical specimen, there was a
      significantly higher proportion of HCC cases graded as poorly differentiated
      (well-differentiated, n = 34; 36.6%; moderately differentiated, n = 33; 35.5%;
      poorly differentiated, n = 26; 27.9%) (P < 0.05). The overall percent agreement
      of NCB and surgical pathology to determine tumor grade was poor (kappa = 0.18, P
      < 0.0001). Whereas final pathologic tumor grade predicted the presence of
      microscopic vascular invasion (well, 15.7%; moderate; 31.9%, poor; 58.4%; P =
      0.001), NCB grade did not (well, 23.7%; moderate, 28.0%; poor, 25.4%; P = 0.65).
      CONCLUSIONS: Selection of candidates for transplantation based on NCB tumor grade
      may be misleading, as NCB tumor grade often did not correlate with grade or
      presence of microscopic vascular invasion on final pathology. Clinicomorphologic
      criteria (tumor size, number) should remain the major determinants of eligibility
      for transplantation.

PMID- 17435552
TI  - Clinical and economic validation of the International Study Group of Pancreatic
      Fistula (ISGPF) classification scheme.
AB  - OBJECTIVE: The authors sought to validate the ISGPF classification scheme in a
      large cohort of patients following pancreaticoduodenectomy (PD) in a
      pancreaticobiliary surgical specialty unit. SUMMARY BACKGROUND DATA: Definitions
      of postoperative pancreatic fistula vary widely, precluding accurate comparisons
      of surgical techniques and experiences. The ISGPF has proposed a classification
      scheme for pancreatic fistula based on clinical parameters; yet it has not been
      rigorously tested or validated. METHODS: : Between October 2001 and 2005, 176
      consecutive patients underwent PD with a single drain placed. Pancreatic fistula
      was defined by ISGPF criteria. Cases were divided into four categories: no
      fistula; biochemical fistula without clinical sequelae (grade A), fistula
      requiring any therapeutic intervention (grade B), and fistula with severe
      clinical sequelae (grade C). Clinical and economic outcomes were analyzed across
      all grades. RESULTS: More than two thirds of all patients had no evidence of
      fistula. Grade A fistulas occurred 15% of the time, grade B 12%, and grade C 3%.
      All measurable outcomes were equivalent between the no fistula and grade A
      classes. Conversely, costs, duration of stay, ICU duration, and disposition
      acuity progressively increased from grade A to C. Resource utilization similarly
      escalated by grade. CONCLUSIONS: Biochemical evidence of pancreatic fistula alone
      has no clinical consequence and does not result in increased resource
      utilization. Increasing fistula grades have negative clinical and economic
      impacts on patients and their healthcare resources. These findings validate the
      ISGPF classification scheme for pancreatic fistula.

PMID- 17435553
TI  - Morbidity of sentinel lymph node biopsy (SLN) alone versus SLN and completion
      axillary lymph node dissection after breast cancer surgery: a prospective Swiss
      multicenter study on 659 patients.
AB  - OBJECTIVE: To assess the morbidity after sentinel lymph node (SLN) biopsy
      compared with SLN and completion level I and II axillary lymph node dissection
      (ALND) in a prospective multicenter study. SUMMARY BACKGROUND DATA: ALND after
      breast cancer surgery is associated with considerable morbidity. We hypothesized:
      1) that the morbidity in patients undergoing SLN biopsy only is significantly
      lower compared with those after SLN and completion ALND level I and II; and 2)
      that SLN biopsy can be performed with similar intermediate term morbidity in
      academic and nonacademic centers. METHODS: Patients with early stage breast
      cancer (pT1 and pT2 <or= 3 cm, cN0) were included between January 2000 and
      December 2003 in this prospective Swiss multicenter study. All patients underwent
      SLN biopsy. In all patients with SLN macrometastases and most patients with SLN
      micrometastases (43 of 68) or isolated tumor cells (11 of 19), a completion ALND
      was performed. Postoperative morbidity was assessed based on a standardized
      protocol. RESULTS: SLN biopsy alone was performed in 449 patients, whereas 210
      patients underwent SLN and completion ALND. The median follow-ups were 31.0 and
      29.5 months for the SLN and SLN and completion ALND groups, respectively.
      Intermediate-term follow-up information was available from 635 of 659 patients
      (96.4%) of enrolled patients. The following results were found in the SLN versus
      SLN and completion ALND group: presence of lymphedema (3.5% vs. 19.1%, P <
      0.0001), impaired shoulder range of motion (3.5% vs. 11.3%, P < 0.0001),
      shoulder/arm pain (8.1% vs. 21.1%, P < 0.0001), and numbness (10.9% vs. 37.7%, P
      < 0.0001). No significant differences regarding postoperative morbidity after SLN
      biopsy were noticed between academic and nonacademic hospitals (P = 0.921).
      CONCLUSIONS: The morbidity after SLN biopsy alone is not negligible but
      significantly lower compared with level I and II ALND. SLN biopsy can be
      performed with similar short- and intermediate-term morbidity in academic and
      nonacademic centers.

PMID- 17435554
TI  - A declining rate of completion axillary dissection in sentinel lymph node
      positive breast cancer patients is associated with the use of a multivariate
      nomogram.
AB  - OBJECTIVE: To compare sentinel lymph node (SLN)-positive breast cancer patients
      who had completion axillary dissection (ALND) with those who did not, with
      particular attention to clinicopathologic features, nomogram scores, rates of
      axillary local recurrence (LR), and changes in treatment pattern over time.
      BACKGROUND: While conventional treatment of SLN-positive patients is to perform
      ALND, there may be a low-risk subgroup of SLN-positive patients in whom ALND is
      not required. A multivariate nomogram that predicts the likelihood of residual
      axillary disease may assist in identifying this group. METHODS: Among 1960
      consecutive SLN-positive patients (1997-2004), 1673 (85%) had ALND ("SLN+/ALND")
      and 287 (15%) did not ("SLN+/no ALND"). We compare in detail the
      clinicopathologic features, nomogram scores, and rates of axillary LR between
      groups. RESULTS: Compared with the SLN+/ALND group, patients with SLN+/no ALND
      were older, had more favorable tumors, were more likely to have breast
      conservation, had a lower median predicted risk of residual axillary node
      metastases (9% vs. 37%, P < 0.001), and had a marginally higher rate of axillary
      LR (2% vs. 0.4%, P = 0.004) at 23 to 30 months' follow-up; half of all axillary
      LR in SLN+/no ALND patients were coincident with other local or distant sites.
      For patients in whom intraoperative frozen section was either negative or not
      done, the rate of completion ALND declined from 79% in 1997 to 62% in 2003 to
      2004 but varied widely by surgeon, ranging from 37% to 100%. For 10 of 10
      evaluable surgeons, the median nomogram scores in the SLN+/no ALND group were
      <or=10.5. CONCLUSIONS: SLN+/no ALND breast cancer patients, a selected group with
      relatively favorable disease characteristics, had a 9% predicted likelihood of
      residual axillary disease by nomogram but an observed axillary LR of 2%. A
      gradual and significant decline over time in the rate of completion ALND is
      associated with, but not entirely explained by, the institution of a predictive
      nomogram. It is reasonable to omit ALND for a low-risk subset of SLN-positive
      patients.

PMID- 17435555
TI  - Electrochemotherapy: aspects of preclinical development and early clinical
      experience.
AB  - OBJECTIVE: To develop an optimized, reproducible system of electrochemotherapy,
      and to investigate its clinical application in patients with cutaneous or
      subcutaneous recurrences of inoperable or progressive disease recalcitrant to
      current anticancer treatments. BACKGROUND: Electrochemotherapy is the application
      of electric pulses to tumor tissue, rendering the cell membranes permeable to
      otherwise impermeant or poorly permeant anticancer drugs. This facilitates a
      potent local cytotoxic effect. STUDY DESIGN: The optimal parameters for
      electrical pulses and bleomycin concentration were obtained in vitro and then
      applied to tumors derived from 4 histologically distinct human cancer cell lines
      (7860, PC3, OE19, MCF-7) established in athymic nude mice. Comparison was made
      with tumors that received bleomycin alone, electric pulses alone, and untreated
      controls. The optimized electrochemotherapy was then applied to patients with
      cutaneous or subcutaneous tumors, of any histologic type, recurrent or metastatic
      and unresponsive to standard chemotherapy and/or radiotherapy regimens. Tumors
      were assessed at monthly intervals to determine response to the treatment.
      RESULTS: In vivo: Using the optimal parameters ascertained in vitro, all tumors
      treated by electrochemotherapy with bleomycin (n = 24) had significantly
      regressed (P < 0.001, all 4 lines) compared with control tumors (n = 72). Twelve
      tumors completely regressed (50%) following a single application, with 12 partial
      regressions (50%). Clinical: In 30 patients (111 tumors), none of the treated
      tumors progressed. Sixty percent of tumors (66 of 111) showed complete
      regression, 22% (24 of 111) partial response, and 18% (21 of 111) no change.
      Electrochemotherapy was more effective in smaller tumors (<3 cm), 71% (64 of 90)
      showing complete regression, 20% (18 of 90) partial response, and 9% (8 of 90) no
      change. CONCLUSIONS: Electrochemotherapy parameters optimized in vitro are
      applicable in vivo. This treatment is effective in athymic nude mice for all
      histologic types indicating a nonimmunologic mode of action. In clinical
      application, electrochemotherapy is an effective, safe, and reproducible therapy.
      Patients with cutaneous or subcutaneous tumors previously refractory to surgical
      intervention, systemic chemotherapy, and/or radiotherapy responded successfully
      irrespective of histologic type.

PMID- 17435556
TI  - Ghrelin down-regulates proinflammatory cytokines in sepsis through activation of
      the vagus nerve.
AB  - OBJECTIVE: To test the hypothesis that administration of ghrelin attenuates
      inflammatory responses in sepsis through vagal nerve stimulation. SUMMARY
      BACKGROUND DATA: Ghrelin has been demonstrated to possess multiple functions,
      including stimulation of the vagus nerve. Our recent study has shown that plasma
      levels of ghrelin were significantly reduced in sepsis; and ghrelin
      administration improved organ perfusion and function. However, it remained
      unknown whether ghrelin also decreases proinflammatory cytokines in sepsis and,
      if so, whether the down-regulatory effect of ghrelin is mediated by activation of
      the vagus nerve. METHODS: Male rats were subjected to sepsis by cecal ligation
      and puncture (CLP). At 5 hours after CLP, a bolus intravenous injection of 2 nmol
      ghrelin was followed by a continuous infusion of 12 nmol ghrelin via a primed 200
      microL Alzet mini-pump for 15 hours. At 20 hours after CLP, plasma and peritoneal
      fluid levels of TNF-alpha and IL-6 were determined. The direct effect of ghrelin
      on cytokine production was studied using cultured normal rat Kupffer cells or
      peritoneal macrophages stimulated by lipopolysaccharide (LPS). In additional
      animals, vagotomy or sham vagotomy was performed in sham and septic animals
      immediately prior to ghrelin administration and cytokine levels were then
      measured. RESULTS: Ghrelin significantly reduced TNF-alpha and IL-6 levels in
      sepsis. In contrast, ghrelin did not inhibit TNF-alpha and IL-6 release from LPS
      stimulated Kupffer cells or peritoneal macrophages. However, vagotomy, but not
      sham vagotomy, prevented ghrelin's down-regulatory effect on TNF-alpha and IL-6
      production. CONCLUSIONS: Ghrelin down-regulates proinflammatory cytokines in
      sepsis through activation of the vagus nerve. Pharmacologic stimulation of the
      vagus nerve may offer a novel approach of anti-sepsis therapy.

PMID- 17435557
TI  - Somatic and psychologic predictors of long-term unfavorable outcome after
      surgical intervention.
AB  - OBJECTIVE: To identify somatic and psychologic predictors of pain, functional
      limitations, global perceived recovery, and quality of life 6 months after
      surgical intervention. SUMMARY BACKGROUND DATA: Recent studies have indicated
      that chronic pain after surgical intervention is more common than previously
      assumed. Several demographic and somatic predictors of long-term unfavorable
      outcome have been identified, but little is known about the contribution of
      psychologic risk factors. METHODS: A prospective cohort study, including 625
      patients undergoing elective surgery at the University Hospital Maastricht, The
      Netherlands, was conducted between February and August 2003. Psychologic
      questionnaires were completed preoperatively and acute postoperative pain was
      recorded until 4 days after the operation. Six months later, all patients
      received follow-up questionnaires to assess pain, functional limitations, global
      perceived recovery, and quality of life. Multivariable logistic regression
      analyses were used to estimate relative risk of poor outcome in terms of pain,
      functional limitations, and global recovery. Multivariable linear regression
      analysis was used to assess associations with quality of life at 6 months.
      RESULTS: The most important somatic predictors of unfavorable outcome were
      duration of the operation and high levels of acute postoperative pain. Patients
      reporting high levels of pain 4 days after the operation and patients undergoing
      an operation of longer than 3 hours were at risk for increased pain, increased
      functional limitations, poor global recovery, and reported lower levels of
      quality of life 6 months after the operation. Psychologic variables that
      influenced long-term outcome were preoperative fear of surgery and optimism. Fear
      of the long-term consequences of the operation was associated with more pain,
      poor global recovery, and worse quality of life 6 months later, whereas optimism
      was associated with better recovery and higher quality of life. CONCLUSIONS: This
      study was the first to identify the joint contribution of somatic and psychologic
      factors to chronic pain, functional limitations, and quality of life 6 months
      after surgical interventions. It replicates previous findings that intense acute
      postoperative pain is a risk factor for long-term adverse outcome and also
      identified additional risk factors, namely, long duration of the operation, ASA
      status, and preoperative fear of surgery.

PMID- 17435558
TI  - Do modern spectacles endanger surgeons? The Waikato Eye Protection Study.
AB  - BACKGROUND: Despite documented cases of infectious disease transmission to
      medical staff via conjunctival contamination and widespread recommendation of
      protective eyewear use during surgical procedures, a large number of surgeons
      rely on their prescription spectacles as sole eye protection. Modern fashion
      spectacles, being of increasingly slim design, may no longer be adequate in this
      role. METHODS: A survey was conducted among the surgeons at Waikato Hospital from
      December 7, 2004 to February 1, 2005, to assess current operating theater eyewear
      practices and attitudes. Those who wore prescription spectacles were asked to
      assume a standardized "operating position" from which anatomic measurements were
      obtained. These data were mathematically analyzed to determine the degree of
      palebral fissure protection conferred by their spectacles. RESULTS: Of 71
      surgical practitioners surveyed, 45.1% required prescription lenses for
      operating, the mean spectacle age being 2.45 years; 84.5% had experienced prior
      periorbital blood splashes; 2.8% had previously contracted an illness attributed
      to such an event; 78.8% participants routinely used eye protection, but of the 27
      requiring spectacles, 68.0% used these as their sole eye protection. Chief
      complaints about safety glasses and facial shields were of fogging, poor comfort,
      inability to wear spectacles underneath, and unavailability. Our model predicted
      that 100%, 92.6%, 77.8%, and 0% of our population were protected by their
      spectacles laterally, medially, inferiorly, and superiorly, respectively.
      CONCLUSIONS: Prescription spectacles of contemporary styling do not provide
      adequate protection against conjunctival blood splash injuries. Our model
      predicts the design adequacy of currently available purpose-designed protective
      eyewear, which should be used routinely.

PMID- 17435559
TI  - Reflux after Heller's myotomy for achalasia.

PMID- 17435560
TI  - Suicide bombing attacks: can external signs predict internal injuries?

PMID- 17435561
TI  - What does Star*D tell us about ECT?

PMID- 17435562
TI  - Belling the cat: ECT practice standards in the United States.

PMID- 17435563
TI  - Cardiovascular effects of anesthesia in ECT: a randomized, double-blind
      comparison of etomidate, propofol, and thiopental.
AB  - Cardiovascular alterations during electroconvulsive therapy (ECT) are a major
      concern for this treatment. Although several studies have been performed to
      compare the effects of anesthetics on these alterations, the results are mixed
      and doubt still exists regarding the choice of the best drug. We conducted a
      randomized, double-blind clinical trial to compare the effects of 3 anesthetics
      used in ECT: etomidate, propofol, and thiopental. Patients (N=30) were randomized
      to receive one of these drugs as the anesthetic for the ECT procedure.
      Cardiovascular evaluation consisted of the measurement of blood systolic and
      diastolic pressure and heart rate before and immediately after the end of the
      seizure for each patient during a course of ECT. The results showed that
      etomidate, propofol, and thiopental were associated with similar cardiovascular
      effects.

PMID- 17435564
TI  - Blood pressure before and after electroconvulsive therapy in hypertensive and
      nonhypertensive patients.
AB  - The effect of a course of electroconvulsive therapy (ECT) on blood pressure
      control in hypertensive patients has not been studied. We retrospectively
      examined pre- and post-ECT blood pressures in hypertensive and nonhypertensive
      patients. In neither group was there a statistically significant change in blood
      pressure with a course of ECT. We conclude that a course of ECT does not worsen
      blood pressure in hypertensive patients beyond the peritreatment period.

PMID- 17435565
TI  - The prevalence of prolonged cerebral seizures at the first treatment in a course
      of electroconvulsive therapy.
AB  - BACKGROUND: It has been suggested that prolonged cerebral seizures are more
      prevalent in contemporary practice than realized partly because they may go
      undetected in the absence of monitoring by electroencephalogram (EEG). The
      previous report on this topic from Scotland concerned only patients taking part
      in research and may not be generalizable to routine clinical practice; moreover,
      the EEG monitoring was not all carried out at a standardized point in the course
      of treatment. OBJECTIVE: We sought to establish the prevalence of prolonged
      cerebral seizures in a representative sample from routine clinical practice in
      Edinburgh and do so at the first treatment, when the risk is greatest. METHOD:
      Two-channel EEG monitoring was conducted at the first treatment in a new course
      given to 100 individual consecutive patients. RESULTS: The titration had to be
      curtailed for anesthetic reasons in 2 patients, and no cerebral seizure was
      induced. Electroencephalogram measurement of seizure duration was practicable in
      only 95 of the remaining patients. Two cerebral seizures longer than 120 seconds
      were detected. One seizure ended spontaneously after 158 seconds and was
      associated with a generalized convulsion lasting 77 seconds. One was medically
      terminated after 180 seconds and was associated with a generalized convulsion
      lasting 122 seconds; this patient had an encephalopathy during the index illness.
      CONCLUSIONS: The prevalence of prolonged seizures in our routine clinical
      practice was 1% to 2%, depending on the definition of prolonged cerebral seizure
      activity.

PMID- 17435566
TI  - Seizure length in electroconvulsive therapy as a function of age, sex, and
      treatment number.
AB  - Most electroconvulsive therapy (ECT) research indicates that seizure length does
      not correlate with clinical efficacy. However, it is common in practice for
      clinicians to undertake measures to prolong seizures if the duration seems to be
      too short, although there is no universally agreed upon minimum seizure duration
      for ECT. We felt it would be informative for the ECT field to report mean seizure
      durations over the course of treatments based on age and sex in a very large
      cohort to provide norms for reference. We studied 519 patients' courses of ECT
      and recorded treatment number, sex, and age along with motor and
      electroencephalogram seizure duration. We found that women have longer seizures,
      but only at the first treatment session. There is a strong inverse correlation
      between age and seizure length. The biggest drop in seizure duration along a
      course of treatments occurs between the first and second treatments; beyond that,
      seizure duration remains relatively constant.

PMID- 17435567
TI  - Long-term follow-up after successful electroconvulsive therapy for depression: a
      4- to 8-year naturalistic follow-up study.
AB  - OBJECTIVES: A long-term follow-up of depressed patients responsive to
      electroconvulsive therapy (ECT) with intensive pre-ECT pharmacotherapy treatment
      failure who also participated in a 6-month trial directly post-ECT in which
      imipramine was compared with placebo for relapse prevention. METHODS: A total of
      26 patients responsive to ECT who participated in the 6-month continuation trial
      were invited 4 to 8 years later to assess their follow-up status. The groups with
      and without relapse within 6 months were compared with regard to recurrence of
      depression up to 8 years later. Recurrence was defined as a new episode of
      depression that needed antidepressant medication and/or readmission in hospital
      and/or a new ECT course. RESULTS: At the time of follow-up (mean duration, 6.8
      years), the recurrence rate of depression for the total sample was 42.3%. There
      was no significant difference in the recurrence rates and number of recurrences
      between the nonrelapse and relapse groups. The small study population limits
      generalization of the results; the design of the study is naturalistic and
      retrospective. CONCLUSION: In our small sample of depressed patients with
      pharmacotherapy treatment failure, recurrence is not influenced by relapse after
      terminating ECT. Continuation of medication started immediately after ECT seems
      to be an important factor in preventing recurrence.

PMID- 17435568
TI  - Catatonia in autistic twins: role of electroconvulsive therapy.
AB  - Autism and Asperger disorder are pervasive developmental disorders that impair
      social interactions and communications. They are characterized by repetitive and
      stereotyped behaviors. Catatonia, a syndrome which is most often associated with
      schizophrenia and affective disorders, is seen in up to 6% of patients with
      autistic spectrum disorders and in 12% to 17% of adolescents with these
      disorders. Catatonic symptoms in these cases have been responsive to treatment
      with electroconvulsive therapy. We report a case of adolescent identical twins
      with PDD/Asperger disorder who exhibited catatonia and were successfully treated
      with electroconvulsive therapy.

PMID- 17435569
TI  - Rapid relief of severe major depressive disorder by use of preoperative ketamine
      and electroconvulsive therapy.
AB  - Major depressive disorder is a difficult-to-treat and recurrent debilitating
      disorder. All approved somatic treatments for major depression to date require a
      significant time lapse before demonstrating an antidepressant effect. However,
      emerging evidence indicates a potential role for the use of ketamine to rapidly
      relieve symptoms of major depression. We present a case of severe, recurrent
      major depressive disorder that demonstrated marked improvement within 8 hours of
      receiving a preoperative dose of ketamine and 1 treatment of electroconvulsive
      therapy with bitemporal electrode placement. This case is supportive of a role of
      ketamine in relieving symptoms of major depressive disorder rapidly and safely.

PMID- 17435570
TI  - Pulmonary edema after electroconvulsive therapy in a patient treated for long
      standing asthma with a beta2 stimulant.
AB  - A 68-year-old man was scheduled to receive 8 treatments of electroconvulsive
      therapy (ECT) for severe depression. He was being treated for long-standing
      asthma with a beta2 stimulant, clenbuterol hydrochloride, and had experienced no
      asthma attack for 9 years. Although he experienced no adverse consequence in his
      7 treatments, pulmonary edema ensued from his eighth treatment despite no change
      in anesthesia and in the technical parameters of ECT. He was treated with oxygen
      and intravenous hydrocortisone, after which he quickly recovered. Transient
      eosinophilia was observed, but clinical symptoms of asthma did not appear.
      Although the association between pulmonary edema and well-controlled asthma was
      unclear, thiopental as induction of anesthesia or esmolol as poststimulus
      delivery might have played a role in the event. There may be a possibility of
      pulmonary edema even after several uneventful ECT treatments in a patient with
      asthma.

PMID- 17435571
TI  - Treatment of post-electroconvulsive therapy delirium and agitation with
      donepezil.
AB  - Delirium and agitation are commonly encountered after administration of
      electroconvulsive therapy (ECT). Management is generally fairly straightforward,
      although some patients may have a severe, prolonged, or refractory course. We
      recently cared for a 65-year-old man who consistently developed severe and very
      prolonged post-ECT delirium that did not respond to typical pharmacological
      agents; the duration of delirium was dramatically shortened by the addition of
      donepezil. Cholinesterase inhibitors may have a place in mitigating severe and
      prolonged post-ECT delirium.

PMID- 17435572
TI  - Treatment of status epilepticus with electroconvulsive therapy.
AB  - OBJECTIVE: To describe a case in which electroconvulsive therapy (ECT) was used
      successfully to treat refractory status epilepticus (SE) after all
      pharmacological therapies were exhausted. METHODS: A 39-year-old man with no
      seizure history presented in SE secondary to presumed viral encephalitis. His
      seizures remained refractory to medical management, and he was placed in a
      pentobarbital-induced coma. Multiple attempts to wean pentobarbital over the next
      several months failed due to SE relapses. With all standard pharmacological
      therapies exhausted, the patient underwent a series of 3 ECT sessions per day for
      3 consecutive days. Electroencephalogram improvements were noted immediately with
      diffusely slow activity and with a delayed response over time in the patient's
      neurological examination. Twelve months post-ECT, the patient is awake, alert,
      and being managed on antiepileptic medications as outpatient. DISCUSSION: This
      case further illustrates the role of ECT in the treatment of refractory SE.

PMID- 17435573
TI  - ECT in a man with FG syndrome.
AB  - We report on the use of electroconvulsive therapy (ECT) in a 20-year-old man with
      a history of FG syndrome and schizophrenia who demonstrated thought disorder and
      aggression refractory to pharmacological treatment. He received 71 ECT treatments
      over a period of 13 months and demonstrated a marked reduction in aggressive
      behavior. In the 14 months before beginning ECT, the patient spent 189 days in
      the hospital, whereas in the 13 months subsequent to his initial ECT series as an
      inpatient, he was able to be maintained in the community without psychiatric
      hospitalization. This case extends the findings of prior cases documenting the
      alleviation of aggressive behaviors with ECT.

PMID- 17435574
TI  - ECT in patients with arachnoid cysts.
AB  - Electroconvulsive therapy (ECT) is often considered relatively contraindicated in
      patients with intracranial space-occupying lesions, especially those with
      increased intracranial pressure, edema, or mass effect. We describe the safe use
      of ECT in 6 patients with arachnoid cysts. We conclude that such lesions are
      probably not associated with increased morbidity in ECT but that neurological
      evaluation pretreatment is indicated.

PMID- 17435576
TI  - The effect of lamotrigine on electroconvulsive therapy outcomes.

PMID- 17435577
TI  - Electroconvulsive therapy stimulus dose expressed as volume of seizure foci: a
      different perception.

PMID- 17435586
TI  - Giant cell arteritis in northwestern Spain: a 25-year epidemiologic study.
AB  - To continue our investigation of the epidemiology of giant cell arteritis (GCA)
      in southern Europe, we assessed the potential presence of trends, peaks, and
      fluctuations in the incidence of this vasculitis over a 25-year period in the
      Lugo region of northwestern Spain. We also sought to determine whether changes in
      the clinical spectrum of the disease existed. From 1981 to 2005, biopsy-proven
      GCA was diagnosed in 255 Lugo residents. The age- and sex-adjusted annual
      incidence rate was 10.13 (95% confidence interval [CI], 8.93-11.46) per 100,000
      population aged 50 years and older. The mean age +/- SD at the time of diagnosis
      was 75.0 +/- 6.9 years. The annual incidence rate in women (10.23; 95% CI, 8.60
      12.08) was slightly greater than that in men (9.92; 95% CI, 8.19-11.89) (p =
      0.15). The annual incidence rate increased with advancing age up to a maximum of
      23.16 (95% CI, 19.52-27.28) in the 70-79 year age-group. A progressive increase
      in the incidence was observed from 1981 through 2000 (p = 0.001). However, the
      age- and sex-adjusted incidence rate for biopsy-proven GCA in the Lugo region did
      not show peaks in the annual incidence of GCA. Likewise, we observed no seasonal
      pattern for the diagnosis of the disease. Visual ischemic manifestations and
      irreversible visual loss were observed in 57 (22.4%) and 32 (12.5%) of the 255
      patients, respectively. A negative trend manifested by a progressive decline in
      the number of patients with visual ischemic manifestations (p = 0.021) or
      permanent visual loss (p = 0.018) was found over the 25-year period of study. The
      decline in the frequency of visual manifestations of GCA could not be attributed
      to a shorter delay to diagnosis, as no significant differences were observed when
      the delays to diagnosis in the 5 consecutive 5-year periods were compared. In
      conclusion, the current study confirms a progressive increase in the incidence of
      biopsy-proven GCA in northwestern Spain, and suggests that there has been a
      change in the clinical spectrum of the disease.

PMID- 17435587
TI  - Streptococcus pneumoniae infections in 47 hematopoietic stem cell transplantation
      recipients: clinical characteristics of infections and vaccine-breakthrough
      infections, 1989-2005.
AB  - Streptococcus pneumoniae infections can cause serious systemic disease in
      patients following hematopoietic stem cell transplantation (HSCT), and the
      response to pneumococcal vaccine is inadequate in most HSCT recipients. We
      evaluated the clinical spectrum of pneumococcal disease and vaccine-breakthrough
      infections in HSCT recipients at our cancer center in a retrospective analysis of
      all consecutive episodes of S. pneumoniae infection from 1989 through 2005.
      During the study period, 7888 patients underwent HSCT at our center; we
      identified 47 HSCT recipients with 54 S. pneumoniae infections. The overall
      incidence of S. pneumoniae infection was 7 per 1000 HSCTs. The incidence was
      higher in recipients of allogeneic grafts than in recipients of autologous grafts
      (9 vs. 5 per 1000 HSCTs, respectively; p <or= 0.012). Thirty-two of the 47
      patients (68%) had leukemia or lymphoma; 24 patients (51%) had a malignancy that
      was in complete remission. Seventeen patients (36%) had graft-versus-host
      disease, which was chronic in 16. The 54 episodes of S. pneumoniae infection
      occurred 433 +/- 669 days after HSCT; 5 patients (11%) had multiple episodes.
      Four episodes of S. pneumoniae infection occurred within 100 days following
      transplantation (45 +/- 49 d); 2 of these were during the pre-engraftment period
      and 3 were nosocomial infections. All 50 late post-transplant episodes (93%),
      which occurred 473 +/- 671 days following transplantation, were community
      acquired infections (p < 0.00016). Thirty-three episodes (61%) presented as
      bacteremic pneumonia, 10 (19%) as pneumonia, and 8 (15%) as uncomplicated S.
      pneumoniae bacteremia alone. Logistic regression analysis showed that patients
      receiving systemic corticosteroids had increased risk for bacteremic pneumonia
      (odds ratio [OR], 11.7; 95% confidence intervals [CI], 1.371-99.280; p <or=
      0.025). Patients with lymphoma (OR, 6.101; 95% CI, 1.106-33.640; p <or= 0.04)
      were more likely to develop pneumonia alone. In 27 episodes (93%) among 29 in
      which S. pneumoniae susceptibility testing was performed, the patients received
      concordant antimicrobials. Among the 6 patients (13%) who died of S. pneumoniae
      infection, 4 had S. pneumoniae bacteremic pneumonia and only 1 had chronic GVHD.
      Admission to a critical care unit at the onset of infection (OR, 15.5; 95% CI,
      2.116-113.541; p <or= 0.007) and each unit increase in APACHE II score increase
      the probability of death (OR, 1.9; 95% CI, 1.181-3.054; p <or= 0.008). All 5
      (11%) patients who developed vaccine-breakthrough S. pneumoniae infection (546 +/
      732 d following vaccination) had pneumonia, and in 4 patients concurrent
      bacteremia also occurred. A serious S. pneumoniae infection in HSCT recipients
      occurred more commonly in patients with lymphoma and patients receiving high-dose
      systemic corticosteroid therapy. It is noteworthy that there were no cases of
      extrapulmonary organ infection in HSCT recipients who presented with S.
      pneumoniae infection at our institution.

PMID- 17435588
TI  - Cryptococcosis and idiopathic CD4 lymphocytopenia.
AB  - We reviewed the cases of 11 patients with cryptococcosis and idiopathic CD4
      lymphocytopenia (ICL) referred to our institution in the previous 12 years, as
      well as 42 similar cases reported in the literature, to assess the
      characteristics of the infection in this population. Cryptococcosis in 53
      patients with ICL had features in common with cryptococcosis in previously normal
      patients. ICL patients had a slight male predominance (1.2:1) and a median age of
      presentation of 41 years (range, 4.5-85 yr). Initial cerebrospinal fluid findings
      showed glucose below 40 mg/dL in 60% of the patients, a median pleocytosis of 59
      white blood cells/mm (range, 0-884), and protein of 156 mg/dL (range, 25-402
      mg/dL). The median CD4 count at diagnosis of ICL and at the last available
      measurement was 82 (range, 7-292) and 132 (range, 13-892) cells/mm, respectively,
      for an average follow-up of 32 months in 46 patients. Unlike previously normal
      patients with cryptococcosis, those with ICL had an excess incidence of
      dermatomal zoster (7 episodes in 46 ICL cases). Pneumocystis pneumonia was rare
      (1 case), casting doubt on the need for prophylaxis in patients with ICL. A
      favorable outcome (cured or improved) may be more common in ICL patients than in
      previously normal patients with cryptococcal meningitis and no predisposing
      factors. Identification of ICL in patients who were apparently normal before the
      onset of cryptococcosis appears to be useful because it predicts a favorable
      outcome. Patients with cryptococcal infection and ICL have an increased
      likelihood of developing dermatomal zoster. The long-term follow-up of these
      patients offers some reassurance regarding favorable prognosis.

PMID- 17435589
TI  - Long-term outcome in Susac syndrome.
AB  - Susac syndrome is characterized by the clinical triad of encephalopathy, hearing
      loss, and retinal artery branch occlusions, mostly in young women. To our
      knowledge, long-term outcome and impact of pregnancy have not been specifically
      addressed. We report a series of 9 patients (7 female, 2 male) followed at the
      same institution, with special emphasis on clinical outcome including pregnancy
      and long-term sequelae. Clinical, brain magnetic resonance imaging (MRI),
      funduscopy, retinal angiography, and audiogram data were recorded every 3-12
      months. We also analyzed the 92 previously reported cases of Susac syndrome. Mean
      follow-up was 6.4 years. Age at onset was 30.4 years. The first symptom occurred
      between April and September in 7 of 9 patients in the current study, and in 68%
      of all patients. The complete triad at onset was clinically obvious in only 1 of
      9 patients. Brain involvement was heralded by headache and symptoms of
      encephalopathy. Cerebrospinal fluid was abnormal in 5 patients showing
      pleocytosis (mean, 24.6; range, 6-85 cells/mL) and elevated protein level (mean,
      210; range, 113-365 mg/dL). Over time, quantitative brain MRI analysis showed
      that the number of lesions diminished and did not parallel clinical flares, and
      MRI never normalized. At the end of follow-up, no patient had severe impairment,
      and all but 1 returned to work. Inner ear involvement was present at onset in 2
      patients and occurred in others with a mean delay of 11 months. Initially
      unilateral in 3, it became bilateral in all. Mean hearing loss was 34 dB (range,
      15-70 dB). Hearing loss never improved, either spontaneously or under treatment.
      The eye was involved at onset in 8 patients, and after 3 years in 1. All had
      multiple bilateral retinal artery branch occlusions and/or dye leakage with
      hyperfluorescence of the arterial wall on fluorescein angiography. Over time,
      angiography normalized in 3 patients. In others, it was still abnormal at the end
      of follow-up (range, 1.5-10 yr). On late findings, fluorescein leakage was more
      frequent than true arterial occlusion. Eye involvement was mostly asymptomatic,
      unilateral, peripheral, and resumed spontaneously to remit in other sites over
      time. Corticosteroids were efficient to treat encephalopathy, with relapses
      occurring when the dosage was tapered. Steroid treatment did not improve hearing
      loss or prevent new retinal arteriolar occlusions. Anticoagulation had a role in
      treating encephalopathy and retinal arteriolar occlusions. Three patients had 4
      pregnancies. Two pregnancies needed induced abortion. One pregnancy was
      uneventful. One pregnancy was complicated with Susac disease flare in the early
      postpartum period. In conclusion, at the end of follow-up, most patients had
      returned to work and none had severe impairment. Pregnancy may affect the course
      of Susac syndrome, with relapse of encephalopathy postpartum. Our main finding
      was that the course of Susac syndrome is not self-limited as previously thought,
      since isolated retinal arteriolar involvement may occur as a very late
      manifestation.

PMID- 17435590
TI  - Community-acquired pneumonia requiring admission to an intensive care unit: a
      descriptive study.
AB  - Severe community-acquired pneumonia (CAP) requiring admission to an intensive
      care unit (ICU) has been inadequately studied. We compared characteristics and
      outcomes of patients with CAP who were admitted to the ICU with those of patients
      managed on the ward. Of the 3675 patients hospitalized with CAP, 374 (10%) were
      admitted to the ICU. The main reason for ICU admission was respiratory failure
      requiring intubation and ventilation (n = 303, 81%), although this indication
      decreased with increasing age (p < 0.05 for trend). Most patients (62%) required
      mechanical ventilation for 3 days or less. The following factors were predictive
      of ICU admission on multivariable analysis: younger age, smoker, limitation of
      functional status, absence of cough or pleurisy, presence of chronic obstructive
      pulmonary disease, substance abuse, elevated serum creatinine, abnormal serum
      glucose concentration, and a respiratory rate of <16 or >24 breaths per minute.
      Patients with low Pneumonia Severity Index scores and low CURB-65 scores were
      admitted to the ICU based on clinical judgment that appeared to supersede
      objective scoring. Severe CAP requiring admission to the ICU is common, and the
      decision about which patients to admit often requires clinical judgment that in
      many cases appears at odds with various validated pneumonia severity scoring
      systems.

PMID- 17435591
TI  - Wilson disease: description of 282 patients evaluated over 3 decades.
AB  - The clinical manifestations of Wilson disease (WD) are varied and challenging. We
      conducted the current study to present the phenotypic characteristics and follow
      up for a large cohort of patients with WD. We reviewed the medical records of 282
      cases of WD (male:female ratio, 196:86) for clinical features, investigations,
      treatment, and outcome data. The clinical presentations were as follows: hepatic,
      42 (14.9%); hepato-neurologic, 10 (3.5%); neurologic, 195 (69.1%); pure
      psychiatric, 7 (2.4%); osseomuscular, 6 (2.1%); and "presymptomatic," 15 (5.3%).
      Mean age was 15.9 years. Presymptomatic patients and those with the hepatic form
      of WD were younger and patients with osseomuscular and psychiatric forms were
      older than neurologic patients. The mean duration of illness at the time of
      diagnosis was 28 months. Predominant neurologic features were as follows:
      parkinsonism, 62.3%; dystonia, 35.4%; cerebellar, 28%; pyramidal signs, 16%;
      chorea, 9%; athetosis, 2.2%; myoclonus, 3.4%; and behavioral abnormalities, 16%.
      Kayser-Fleischer (KF) rings were seen as follows: neurologic patients, 100%;
      hepatic patients, 86%; and presymptomatic patients, 59%. Positive family history
      was noted in 47% and consanguinity in 54%. Patients born of consanguineous
      parents had an earlier age of onset and shorter duration of illness before
      presentation. Serum ceruloplasmin was decreased in 93% and 24-hour urinary copper
      excretion was increased in 70% of patients. Neuroimaging (computed
      tomography/magnetic resonance imaging) and electrophysiologic abnormalities were
      seen in many patients. Overall, 195 patients were on D-penicillamine therapy and
      182 on zinc sulphate. Follow-up data, available for 225 patients, for a mean
      duration of 46 months, revealed improvement in 176, no change in 20, and
      deterioration in 6. Twenty-three patients died. To conclude, despite increased
      awareness and recognition and significant inroads into therapeutic frontiers,
      follow-up remains poor in developing countries and a return to previous level of
      functioning is not universal.

PMID- 17435592
TI  - Interictal alterations of the trigeminal somatosensory pathway and periaqueductal
      gray matter in migraine.
AB  - Migraine has been traditionally considered a nonprogressive, paroxysmal disorder
      with no brain abnormalities between attacks. We used diffusion tensor imaging to
      examine interictal diffusion properties of the brains of migraineurs with aura,
      migraineurs without aura and matched healthy controls. Areas of lower fractional
      anisotropy were present in migraineurs along the thalamocortical tract. In
      addition, migraineurs with aura had lower fractional anisotropy in the ventral
      trigeminothalamic tract, and migraineurs without aura had lower fractional
      anisotropy in the ventrolateral periaqueductal grey matter. Our results indicate
      the presence of permanent interictal changes in migraineurs, pointing to an
      effect of migraine on the trigeminal somatosensory and modulatory pain systems.

PMID- 17435593
TI  - Rotenone and MPP+ preferentially redistribute apoptosis-inducing factor in
      apoptotic dopamine neurons.
AB  - Rotenone and 1-methyl-4-phenylpyridinium produce parkinsonian models and we
      determined whether their mitochondrially mediated actions differentially
      redistributed the apoptogenic proteins, apoptosis-inducing factor and cytochrome
      c. Cultured rat mesencephalic dopamine neurons were exposed to rotenone (30 nM)
      and 1-methyl-4-phenylpyridinium (300 muM, 24 and 48 h) and apoptosis and
      mitochondrial redistribution of cytochrome c or apoptosis-inducing factor were
      quantified. Tyrosine hydroxylase-positive dopamine neurons underwent apoptosis
      (shrinkage, less neurites) and 40% released apoptosis-inducing factor with
      rotenone (24 h), whereas cytochrome c release reached this value at 48 h when 70%
      of cells had released apoptosis-inducing factor-positive. 1-Methyl-4
      phenylpyridinium produced similar redistribution patterns for both proteins.
      Preferential redistribution of apoptosis-inducing factor before cytochrome c in
      dopamine neurons indicates caspase-independent mitochondrial proapoptotic
      signalling predominates in these parkinsonian models.

PMID- 17435594
TI  - Localization of the active zone proteins CAST, ELKS, and Piccolo at neuromuscular
      junctions.
AB  - CAST and ELKS are major components of the presynaptic active zones of neurons in
      the central nervous system, but it remains elusive whether CAST and ELKS are also
      components of synapses in the peripheral nervous system. Here, we have attempted
      to examine their expression and localization at the synapses of neuromuscular
      junctions. Immunoreactivity for ELKS is partly colocalized with that for the
      major neuromuscular junctions marker alpha-bungarotoxin, which binds to
      acetylcholine receptors. Moreover, another active zone protein, Piccolo, is also
      present at neuromuscular junctions, together with ELKS, whereas CAST is not
      found. These results suggest that at least ELKS and Piccolo, but not CAST, are
      components of neuromuscular junction synapses in the peripheral nervous system.

PMID- 17435595
TI  - Declarative memory formation in hippocampal sclerosis: an intracranial event
      related potentials study.
AB  - The functional deficits associated with hippocampal sclerosis during declarative
      memory formation are largely unknown. In this study, we analyzed intracranial
      event-related potentials recorded from the medial temporal lobes of nine epilepsy
      patients performing a word memorization task. We used frequency-specific wavelet
      analysis to assess stimulus-related changes in power and intertrial phase
      coherence. Statistical analysis revealed a significant decrease of stimulus
      induced power in the delta and theta range on the side of pathology. No
      significant differences in phase locking were observed. Findings indicate a
      reduced availability of recruitable neural assemblies not only in the hippocampus
      but also in the rhinal cortex during memory formation. Network functions related
      to the timing of neural responses to the stimulus appear to be preserved.

PMID- 17435596
TI  - The human 'pitch center' responds differently to iterated noise and Huggins
      pitch.
AB  - A magnetoencephalographic marker for pitch analysis (the pitch onset response)
      has been reported for different types of pitch-evoking stimuli, irrespective of
      whether the acoustic cues for pitch are monaurally or binaurally produced. It is
      claimed that the pitch onset response reflects a common cortical representation
      for pitch, putatively in lateral Heschl's gyrus. The result of this functional
      MRI study sheds doubt on this assertion. We report a direct comparison between
      iterated ripple noise and Huggins pitch in which we reveal a different pattern of
      auditory cortical activation associated with each pitch stimulus, even when
      individual variability in structure-function relations is accounted for. Our
      results suggest it may be premature to assume that lateral Heschl's gyrus is a
      universal pitch center.

PMID- 17435597
TI  - Alterations in right posterior hippocampus in early blind individuals.
AB  - This study compares hippocampal volumes of early blind and sex/age-matched
      sighted controls through volumetric and localization analyses. Early blind
      individuals showed a significantly smaller right posterior hippocampus compared
      with controls. No differences in total hippocampal volumes were found between
      groups and there were no within-group differences for left versus right
      hippocampus. Sex, age and total brain grey matter volume had no effect on
      hippocampal volumes. Although extensive navigational training results in
      structural enhancement of the hippocampus for the sighted, the reduction of the
      posterior hippocampus in early blind individuals suggests the implication of this
      region in visual spatial memory.

PMID- 17435598
TI  - Brain response to birdsongs in bird experts.
AB  - Auditory expertise has mostly been studied in relation to musical processing, but
      expert auditory processing can also involve nonmusical auditory stimuli, such as
      birdsongs in bird experts. In this study, the neural correlates of bird expertise
      were investigated by using electroencephalography to measure auditory-evoked
      potentials in bird experts and novices. Auditory stimuli in three categories
      (birdsongs, environmental sounds and voices) were presented in a pseudo-random
      order while participants performed a simple target detection task (pure tone). We
      observed similar amplitudes and distributions of the N100-component in bird
      experts and novices. In contrast, the amplitude of the P200 component was
      significantly smaller in bird experts at the Pz and Cz electrodes, reflecting a
      more frontal topography of this positivity. Notably, this group difference was
      observed not only for birdsongs, but also for voices and environmental sounds,
      suggesting a general processing difference in bird experts, not restricted to the
      category of expertise.

PMID- 17435599
TI  - Increased functional magnetic resonance imaging activity during nonconscious
      perception in the attentional blink.
AB  - Presenting two targets for identification within a few hundred milliseconds
      reliably yields reduced performance on the second relative to the first. This
      attentional blink phenomenon has been extensively studied behaviourally but,
      until recently, has eluded direct investigation by functional magnetic resonance
      imaging. The few published imaging studies agree that the attentional blink
      recruits a fronto-temporo-parietal 'attentional' network. What remains
      controversial is the specific role played by the 'object processing' ventro
      occipital regions of the brain. Two studies used different tasks and stimulus
      onset asynchronies leaving the cause for this divergence unknown. The present
      study resolves this discrepancy by examining the different methodologies. Our
      results suggest that task difficulty and masking must be factored in to any
      conclusions drawn about the brain activity during the attentional blink paradigm.

PMID- 17435600
TI  - Conscious access to the unisensory components of a cross-modal illusion.
AB  - It is often claimed that binding information across sensory modalities leads to
      coherent, unitary mental representations. The dramatic illusions experienced as a
      result of intersensory conflict, such as the McGurk effect, are often attributed
      to a propensity of the perceptual system to impose multisensory coherence onto
      events originating from a common source. In contrast with this ssumption of
      unity, we report an unexpected ability to resolve the timing between sound and
      sight regarding multisensory events that induce an illusory reversal of the
      elements specified in each modality. This finding reveals that the brain can gain
      access, simultaneously, to unisensory component information as well as to the
      result of the integrated multisensory percept, suggesting some degree of
      penetrability in the processes leading to cross-modality binding.

PMID- 17435601
TI  - The potential use of bone marrow stromal cells for cochlear cell therapy.
AB  - This study investigated the potential of bone-marrow stromal cell transplantation
      for cell replacement therapy in the cochlea. Bone-marrow stromal cells labeled
      with enhanced green fluorescent protein were injected into the perilymphatic
      space of normal cochleae in mice. Histological analysis 2 weeks after
      transplantation demonstrated that transplanted cells settled within the cochlear
      tissues, especially in the spiral ligament and the spiral limbus, although most
      transplants were located in the perilymphatic space. Some of the transplanted
      cells expressed the cochlear gap-junction protein connexin 26. These findings
      indicate the potential of bone-marrow stromal cells for delivering therapeutic
      molecules and for the restoration of cochlear cells, particularly in the spiral
      ligament and the spiral limbus.

PMID- 17435602
TI  - Localization of hyaluronan in the optic pathway of mouse embryos.
AB  - CD44 has been shown to be involved in midline crossing and the generation of
      ipsilateral projections in the mouse optic chiasm. To determine whether these
      functions involve hyaluronan, the major ligand of CD44, we examined localization
      of hyaluronan in the mouse optic pathway. Hyaluronan was deposited mainly in
      vitreal regions of the retina and the optic disk. In ventral diencephalon, it was
      localized largely on the chiasmatic neurons that project processes to the
      chiasmatic midline and the optic tract. Colocalization of hyaluronan and CD44 was
      observed only in the midline but not lateral domains of the chiasmatic neurons,
      suggesting a hyaluronan/CD44-mediated mechanism that controls axon routing at the
      midline but not at the optic tract and the retina.

PMID- 17435603
TI  - Retinoic acid induces functional c-Ret tyrosine kinase in human neuroblastoma.
AB  - After the treatment of human neuroblastoma SH-SY5Y cells with retinoic acid for
      24 h, the expression of c-Ret receptor tyrosine kinase was greatly elevated.
      Treatment of SH-SY5Y cells with glial cell line-derived neurotrophic factor under
      serum-free conditions after incubation of cells with retinoic acid resulted in
      the phosphorylation of c-Ret receptor tyrosine kinase, with subsequent
      morphological changes that included formation of neurites and rounding of cell
      bodies within 24-48 h. The number of neurite-bearing cells decreased with
      increasing concentrations of mitogen-activated protein kinase-specific and
      phosphatidylinositol 3-kinase inhibitors. These observations suggest that
      retinoic acid induces the expression of glial cell line-derived neurotrophic
      factor-responsive c-Ret receptor tyrosine kinase and that a glial cell line
      derived neurotrophic factor-c-Ret receptor tyrosine kinase-induced signal
      transduction system that might be involved in neurite outgrowth via pathways that
      include phosphatidylinositol 3-kinase and mitogen-activated protein kinase.

PMID- 17435604
TI  - Graded cue information in dichotic pitch: effects on event-related potentials.
AB  - To determine whether electroencephalogram components elicited by dichotic pitch
      stimuli are all-or-none threshold-like responses or graded responses that depend
      on the saliency of the stimuli, we recorded electroencephalograms while
      participants listened to dichotic pitch stimuli constructed with different signal
      to-background ratios. The object-related negativity and P400 components were
      largest when the dichotic pitch was most salient (high signal-to-background
      ratio), and decreased in amplitude with decreasing signal-to-background ratio.
      These results are similar to those reported for mistuned harmonics, thereby
      providing additional evidence that the object-related negativity and P400
      components observed for these disparate stimulus types reflect similar
      processing. They also support the notion that the object-related negativity and
      P400 amplitudes are dependent on the level of relevant cue-based stimulus
      information.

PMID- 17435605
TI  - Similar facial electromyographic responses to faces, voices, and body
      expressions.
AB  - Observing facial expressions automatically prompts imitation, as can be seen with
      facial electromyography. To investigate whether this reaction is driven by
      automatic mimicry or by recognition of the emotion displayed we recorded
      electromyograph responses to presentations of facial expressions, face-voice
      combinations and bodily expressions, which resulted from happy and fearful
      stimuli. We observed emotion-specific facial muscle activity (zygomaticus for
      happiness, corrugator for fear) for all three stimulus categories. This indicates
      that spontaneous facial expression is more akin to an emotional reaction than to
      facial mimicry and imitation of the seen face stimulus. We suggest that seeing a
      facial expression, an emotional body expression or hearing an emotional tone of
      voice all activate the affect program corresponding to the emotion displayed.

PMID- 17435606
TI  - Adaptation of neuromagnetic N1 without shifts in dipolar orientation.
AB  - 306-channel magnetoencephalography, coregistered with high-resolution volumetric
      magnetic resonance imaging, was used with 10 healthy participants to test if
      repetition adapts subsequent processing of sounds in a sequence and whether this
      adaptation influenced the orientation of the dipolar sources in the auditory
      cortex. Auditory N1m responses to 1 kHz pure tones were indexed by clusters of
      sensors situated bilaterally over the temporal lobes. N1m was augmented in
      amplitude at an interstimulus interval of 16 s relative to 1 s. This
      neuromagnetic amplitude augment occurred in dipoles in the vicinity of the
      auditory cortex, without significant shifts in the dipolar orientation. Recent
      repetition thus adapts auditory cortical neurons, in a manner subject to recovery
      after a period of silence.

PMID- 17435607
TI  - Movement activity recovers the loss of spines owing to chronic immobilization.
AB  - In chronically movement-restricted Wistar rats, we described a significant
      decrease of spines along apical shafts of layer V cortical pyramids. Current
      study indicates that the liberation at 40 days of rats whose movements had been
      restricted since 20 days of age produces a gradual recovery of the number of
      spines, reaching the control values at 80 days of age and that this process
      occurred faster in the motor than in the sensory cortices. Nevertheless, when
      R(20) rats were liberated at 80 days, the number of spines had not fully
      recovered when rats were 120 days old. Spine recovery is a form of cortical
      experience-dependent plasticity.

PMID- 17435608
TI  - Interferon-gamma-induced expressions of heat shock protein 60 and heat shock
      protein 10 in C6 astroglioma cells: identification of the signal transducers and
      activators of transcription 3-binding site in bidirectional promoter.
AB  - Heat shock protein 60 and heat shock protein 10 are mitochondrial chaperonin
      proteins. Here, we report that the expressions of heat shock protein 60 and heat
      shock protein 10 were upregulated in interferon-gamma-treated C6 astroglioma
      cells, and the 582 bp in the bidirectional promoter of the heat shock protein 60
      and heat shock protein 10 genes is responsible for interferon-gamma-induced
      induction. The induction of heat shock protein 60 and heat shock protein 10 by
      interferon-gamma was virtually abolished by introducing mutations into the
      putative signal transducers and activators of transcription 3-response element in
      the promoter, and the same mutation impaired increment of the signal transducers
      and activators of transcription 3-binding after interferon-gamma treatment.
      Moreover, Rac1 GTPase was required for maximal heat shock protein 10 and heat
      shock protein 60 inductions by interferon-gamma. These results suggest that
      interferon-gamma-induced upregulations of heat shock protein 60 and heat shock
      protein 10 in C6 astroglioma cells are mediated by the signal transducers and
      activators of transcription 3-binding site, localized in the bidirectional
      promoter.

PMID- 17435609
TI  - Increased visual dependence and otolith dysfunction with alcohol intoxication.
AB  - Alcohol intoxication affects the vestibular system and balance control in many
      ways. We have investigated how acute, moderate (blood alcohol concentrations of
      0.06+/-0.01%), and high (0.10+/-0.02%) alcohol intoxication affects the ability
      to perceive the visual horizontal and vertical and the visual field dependence
      measured with the rod and frame tests in 24 healthy participants. Alcohol
      ingestion impaired the ability to use gravitational vestibular cues when
      determining the visual vertical and horizontal, and caused increased visual field
      dependence. With conflicting gravitational and visual information, alcohol seems
      to promote a reweighting in balance control from a vestibular to a more visual
      dependency. Furthermore, the results indicate that alcohol intoxication at these
      levels start instigating a decompensation of minute subclinical vestibular
      asymmetries.

PMID- 17435610
TI  - Distribution of Smoothened at hippocampal mossy fiber synapses.
AB  - The seven-transmembrane receptor Smoothened is essential for hedgehog signal
      transduction. In adulthood, the highest density of Smoothened mRNA is found in
      the granule cell layer of the dentate gyrus. There, Smoothened expression is
      regulated by the synaptic activity involving the glutamatergic transmission. The
      precise localization of Smoothened proteins, however, has not yet been reported.
      Here, we describe Smoothened protein distribution in the hippocampal mossy fibers
      using specific Smoothened antibodies. We provide evidences for their presynaptic
      localization, and using electron microscopy, show that Smoothened is located in
      close association with synaptic vesicles and rarely with the plasma membrane.
      These findings demonstrate that Smoothened is localized presynaptically and
      suggest that Smoothened signal transduction may be implicated in the complex
      aspects of mossy fiber function.

PMID- 17435611
TI  - Comparison of efficacy, tolerability, and cost of iron polymaltose complex with
      ferrous sulphate in the treatment of iron deficiency anemia in pregnant women.
AB  - BACKGROUND: The efficacy of iron polymaltose complex (IPC) in the treatment of
      iron deficiency anemia (IDA) during pregnancy has not been well established, and
      the evidence is inconclusive. AIMS: The aim of the study was to compare efficacy,
      safety, compliance, and cost-effectiveness of IPC with ferrous sulphate (FS) in
      pregnant patients. SETTINGS AND DESIGNS: The randomized, double-blind, parallel
      group study was conducted in the Department of Pharmacology in collaboration with
      the Department of Obstetrics and Gynaecology Postgraduate Institute of Medical
      Education and Research, Chandigarh, India. METHODS: One hundred pregnant women
      aged 20-40 years at 14 to 27 weeks' gestation, with hemoglobin (Hb) < 9 g/dL, and
      serum ferritin < 12 mcg/L, were classified into 2 groups. One group received IPC
      (100 mg elemental iron), and the other group received FS (120 mg elemental iron)
      daily for 8 weeks. At Week 0 and Week 8, Hb, packed cell volume (PCV), mean
      corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular
      hemoglobin concentration (MCHC), serum iron, and serum ferritin were measured.
      Compliance with study medication was determined by pill counting at each visit.
      Cost minimization analysis was done to compare the costs of the 2 treatments.
      STATISTICAL ANALYSIS: Data are expressed as mean -/+ SD. Paired and unpaired 't'
      test were used to analyze differences within groups and between groups. Chi
      square (x2) test was used to analyze primary efficacy parameters and adverse drug
      reactions (ADR). RESULTS: Statistically significant increases in Hb, PCV, MCV,
      MCH, MCHC, serum iron, and serum ferritin levels were seen at the end of 8 weeks
      of treatment in both groups. The overall adverse effects were more common in the
      FS group compared with the IPC group [41 (78%) vs 15 (31%), P < .001]. The
      compliance rate was significantly (P < .05) higher for the IPC (91%) group than
      for the FS (87%) group. The average total cost (direct + indirect) of treatment
      of anemia was comparable between the 2 groups. CONCLUSION: The results of the
      present study suggest that IPC can be considered as a useful alternative
      formulation for the treatment of IDA during pregnancy for those patients who
      cannot tolerate other iron preparations (ferrous form); this is an important
      finding, as compliance is a significant concern during pregnancy.

PMID- 17435613
TI  - Physicians of the future will use online content at the point-of-care to guide
      their decisions. The future is now!

PMID- 17435614
TI  - The time is right for healthcare reform.

PMID- 17435612
TI  - Postmenopausal tibolone therapy: biologic principles and applied clinical
      practice.
AB  - Although the menopause is a generic physiologic event, its biology is variable
      and specific to a given individual. Genetically determined distribution and
      polymorphism of relevant hormone receptors, enzymes, and various cofactors are
      the biologic mechanisms controlling an individual's clinical response to
      endogenous and prescribed hormones. Advances in molecular biology have led to the
      development of newer pharmacologic agents that are tailored to meet specific
      therapeutic objectives, based on the hormonal biology of relevant organs.
      Tibolone, an analogue of the progestin, norethynodrel, is a drug with tissue
      specific effects on receptors and enzymes that influences the synthesis and
      metabolism of endogenous estrogen, progesterone, and androgen. This is achieved
      via the intestinal bioconversion of tibolone into metabolites that have tissue
      specific agonistic and/or antagonistic estrogenic (3alpha and 3beta
      hydroxytibolone) and progestogenic/androgenic (delta4 tibolone) properties. The
      postmenopausal synthesis and metabolism of estrogen and androgen are briefly
      reviewed with particular reference to sex steroid activity in various target
      organs. On the basis of this hormonal physiology, the clinical utility of
      tibolone is reviewed as a therapeutic agent for the treatment of the symptomatic
      menopause. The effects of tibolone on bone health and osteoporosis,
      cardiovascular disease, the breast, and the endometrium are summarized, and its
      role in clinical practice is reviewed.

PMID- 17435615
TI  - A process and outcomes evaluation of the international AIDS conference: who
      attends? Who benefits most?
AB  - The objective of the study was to conduct a process and outcomes evaluation of
      the International AIDS Conference (IAC). Reaction evaluation data are presented
      from a delegate survey distributed at the 2004 IAC held in Thailand. Input and
      output data from the Thailand IAC are compared to data from previous IACs to
      ascertain attendance and reaction trends, which delegates benefit most, and host
      country effects. Outcomes effectiveness data were collected via a survey and
      intercept interviews. Data suggest that the host country may significantly affect
      the number and quality of basic science IAC presentations, who attends, and who
      benefits most. Intended and executed HIV work-related behavior change was
      assessed under 9 classifications. Delegates who attended 1 previous IAC were more
      likely to report behavior changes than attendees who attended more than 1
      previous IAC. The conference needs to be continually evaluated to elicit the
      required data to plan effective future IACs.

PMID- 17435616
TI  - Oaths for physicians--necessary protection or elaborate hoax?
AB  - The ritual of taking an oath upon graduating from medical school is, with a few
      exceptions, a routine requirement for graduation. Albeit that many students
      believe that they have taken the Hippocratic Oath, this is virtually never the
      case. Very often students themselves write many of these oaths, and taking such
      an oath impresses the student as well as the public, who are potential patients.
      It sketches the ethically proper way for physicians to treat their patients. Such
      an oath is meaningful only when it is not coerced but in reality sketches the
      physicians' obligations toward patients, society, and each other. The question
      and problem of a coerced oath are discussed. It is concluded that students when
      first entering medical school know that such an oath will be a requirement for
      graduation, and because much of the time the persons taking the oath are writing
      it, I believe that coercion is not a factor. It is an unfortunate fact that
      throughout the nation students who are known to behave in ethically inappropriate
      ways are nevertheless allowed to graduate. Possible ways of addressing this
      troubling situation are discussed. Equally troublesome is the fact that we who
      administer the oath as well as the students who swear to it are aware that the
      system of medical care makes it extremely difficult and at times impossible to
      truly adhere to the full implications of this oath. According to the oath,
      physicians (in virtually all formulations) swear that social standing (and by
      implication economic factors) will not change the way in which patients are
      treated. This becomes impossible when uninsured patients are sent away at the
      front desk long before the physician can interact with them. Furthermore, the
      current fact that physicians often are confronted with not doing what they
      consider a necessary test (or prescribe what they think would be the best
      medication) raises the problem of either lying or suggesting to the patient that
      he/she do so--a fact that in the long run cannot help but damage the physician's
      veracity and the trust which patients put in their physicians. That virtually all
      codes of the American Medical Association (AMA) as well as the various
      specialties insist that physicians work toward universal access is stressed.

PMID- 17435617
TI  - Consumers are ready to accept the transition to online and electronic records if
      they can be assured of the security measures.
AB  - BACKGROUND: Healthcare has entered the electronic domain. This domain has
      improved data collection and storage abilities while allowing almost
      instantaneous access and results to data queries. Furthermore, it allows direct
      communication between healthcare providers and health consumers. The development
      of privacy, confidentiality, and security principles are necessary to protect
      consumers' interests against inappropriate access. Studies have shown that the
      health consumer is the important stakeholder in this process. With the
      international push toward electronic health records (EHRs), this article presents
      the importance of secure EHR systems from the public's perspective. OBJECTIVE: To
      examine the public's perception of the security of electronic systems and report
      on how their perceptions can shape the building of stronger systems. METHODS: A
      cross-sectional survey (September-November 2005) of people attending healthcare
      providers (n = 400) was conducted in the 4 major cities in New Zealand.
      Participants were surveyed on computer use, knowledge of EHR-proposed benefits
      and issues, security issues, and demographics. RESULTS: A total of 300 surveys
      were completed and returned (a 75% response rate), with 180 (60%) being women.
      One hundred eighty-eight (62.6%) had not heard of EHRs, with those who had heard
      of them indicating that they were a positive innovation in the health sector.
      However, 202 (73.3%) participants were highly concerned about the security and
      privacy of their health records. This feeling was further accentuated when
      participants were asked about security of electronic systems. Participants were
      worried about hackers (79.4%), vendor access (72.7%), and malicious software
      (68%). Participants were also introduced to various security systems, and in each
      case, over 80% of participants believed that these would make EHR systems more
      secure. A number of chi-square tests were carried out with each variable, and it
      was found that there were strong relationships between age, location, computer
      use, EHR knowledge, and the concern for privacy and the security of medical
      records (P < .05). The survey also showed that there was a very small difference
      (9.8%) between health consumers who believed that paper records are more secure
      than EHRs and those who believed otherwise. CONCLUSIONS: The findings showed that
      for the EHR to be fully integrating in the health sector, there are 2 main issues
      that need to be addressed: The security of the EHR system has to be of the
      highest level, and needs to be constantly monitored and updated. The involvement
      of the health consumer in the ownership and maintenance of their health record
      needs to be more proactive. The EHR aims to collect information to allow for
      "cradle to the grave" treatment; thus, the health consumer has to be seen as a
      major player in ensuring that this can happen correctly. The results from this
      study indicated that the consumer is ready to accept the transition, as long as
      one can be assured of the security of the system.

PMID- 17435618
TI  - We may be able to stop common lethal secretory diarrhea by activating the
      intestinal calcium sensing receptors.

PMID- 17435619
TI  - Case files from Stanford University Medical Center: ten years of HAART: a long
      wait for full HIV suppression.

PMID- 17435620
TI  - Insomnia: zolpidem extended-release for the treatment of sleep induction and
      sleep maintenance symptoms.
AB  - Insomnia impairs daytime functioning or causes clinically significant daytime
      distress. The consequences of insomnia, if left untreated, may contribute to the
      risks of developing additional serious conditions, such as psychiatric illness,
      cardiovascular disease, or metabolic issues. Furthermore, some comorbidities
      associated with insomnia may be bidirectional in their causality because
      psychiatric and other medical problems can increase the risk for insomnia.
      Regardless of the serious consequences of inadequately treated insomnia,
      clinicians often do not inquire into their patients' sleep habits, and patients,
      in turn, are not forthcoming with details of their sleep difficulties. The
      continuing education of physicians and patients with regard to insomnia and
      currently available therapies for the treatment of insomnia is, therefore,
      essential. Insomnia may present as either a difficulty falling asleep, difficulty
      maintaining sleep, or waking too early without being able to return to sleep.
      Furthermore, these symptoms often change over time in an unpredictable manner.
      Therefore, when considering a sleep medication, one with efficacy for the
      treatment of multiple insomnia symptoms is recommended. A modified-release
      formulation of zolpidem, zolpidem extended-release, has been approved for the
      treatment of insomnia characterized by both difficulty in falling asleep and
      maintaining sleep. Here, we review studies supporting the use of zolpidem
      extended-release in the treatment of sleep-onset and sleep maintenance
      difficulties.

PMID- 17435621
TI  - Assessing the effectiveness of informational video clips on Iranian immigrants'
      attitudes toward and intention to use the BC HealthGuide Program in the greater
      Vancouver area.
AB  - BACKGROUND: Consumer-directed health information resources hold great potential
      for improving public health and easing the demand on health systems. Their value,
      however, depends largely on the ability of their intended users to access and use
      them effectively. Little is known about whether British Columbia's ethnocultural
      communities are using the British Columbia (BC) Ministry of Health's BC
      HealthGuide (BCHG) program, and if so, when and for what purposes they use the
      services, as well as level of satisfaction with and users' perceptions of the
      resources. This study investigated attitudes toward and perceptions of the BCHG
      program, as well as use patterns and satisfaction levels, within the Iranian
      community of the Greater Vancouver Area (GVA)--among BC's largest and fastest
      growing Middle Eastern immigrant communities--and explored a model for
      introducing the BCHG program to ethnic communities in the GVA and BC. METHODS: In
      a 2-stage quasi-experimental design, with a combination of quantitative and
      qualitative research methods, data obtained from structured telephone surveys, in
      person interviews, and focus groups involving a randomly selected sample of the
      target population were analyzed before and after intervention with audiovisual
      health information: a series of culturally relevant informative video clips
      developed by direct participation of the community and aired on local television
      channels in the fall of 2004. KEY FINDINGS: There was low awareness and low
      utilization of the BCHG program among participants at the beginning of this
      study. Furthermore, many participants in the initial stage of this study
      cautioned that self-care resources in general are unsuited to Iranian culture,
      due to widespread distrust of health advice received via telephone or the
      Internet, and due to the strong value placed on health advice received directly
      from a professional medical doctor. Nonetheless, attitudes, perceptions, and self
      reported utilization rates of the BCHG program improved substantially among the
      participants of this study following the screening of culturally appropriate,
      targeted promotional videos. Participants almost unanimously reported that
      watching the videos had encouraged them to use the BCHG program, and that they
      intended to promote the resources to others. In addition, the majority of
      participants who had accessed at least one of the BCHG program resources reported
      being satisfied with the services that they had received, and improved
      utilization rates were maintained at the follow-up focus group stage. At the same
      time, participants cautioned that gaining the confidence of the wider Iranian
      community in BC and increasing service utilization will require considerable time
      and effort. In particular, they suggested using a variety of media and
      communication channels, carefully selecting the health messengers, and targeting
      messages to specific community subgroups. CONCLUSIONS: The findings of this study
      strongly suggest that Iranians living in the GVA are open to alternatives to
      routine healthcare services, including the use of preventive and self-care
      resources. However, awareness levels and utilization rates of the BCHG program
      among the GVA's Iranian immigrant population have until now been low. The
      noticeable and sustained improvement to attitudes, perceptions, and self-reported
      utilization rates of the BCHG program among Iranian participants in this study
      after watching culturally appropriate promotional videos indicates the potential
      to modify cultural beliefs in regard to the delivery of preventive health
      information if the relevant messages are delivered appropriately. By carefully
      considering the demographic and cultural characteristics of the various ethnic
      communities living in BC, and by targeting promotional activities and services
      directly to these individual communities, the BCHG program could improve
      awareness and utilization rates within these communities.

PMID- 17435622
TI  - Every clinician deserves an un-sales rep.

PMID- 17435623
TI  - Guidelines and rules: friend or foe?

PMID- 17435624
TI  - Studies on parasitologic and haematologic activities of an enaminone derivative
      of 4-hydroxyquinolin-2(1H)-one against murine schistosomiasis mansoni.
AB  - The activity of a novel enaminone derivative of 4-hydroxyquinoline, BDHQ, was
      screened for its effectiveness against murine schistosomiasis by electron
      microscopy and parasitologic studies. The correlation of these studies with serum
      levels of IFN-gamma and IgE is described. Two groups of 10 mice each were treated
      with different doses of BDHQ, and their results were correlated with the control
      and praziquantel (PZQ)-treated groups. Parasitologic study revealed significant
      reduction in mature worms and tissue egg loads in BDHQ- and PZQ-treated groups,
      whereas immature worms revealed significant reduction in BDHQ groups only. The
      group treated with a higher dose of BDHQ showed significant reductions in
      intestinal ova count when compared with the PZQ-treated group. Ultrastructural
      examination of the worm revealed significant degeneration of the spines and
      tegument in all treated groups, while the genital system was affected in BDHQ
      treated groups only. BDHQ showed considerable effect on cellular activation where
      serum levels of IFN-gamma were significantly increased in comparison to control,
      while anti-soluble worm antigen preparation (SWAP) IgE was significantly
      increased in comparison to both the control and PZQ-treated groups.
      Ultrastructural examination revealed cellular activation in buffy coat and the
      liver in both the BDHQ- and PZQ-treated groups in comparison to the untreated
      one, whereas in the bone marrow and spleen, evidence of cellular activation was
      remarkable in the BDHQ-treated groups. In conclusion, BDHQ exhibits high levels
      of activity against adult and juvenile stages of these parasites, which may be
      due to its mixed cellular and humoral immunologic mechanisms, as demonstrated by
      the significant increase of serum levels of IgE and IFN-gamma shown on electron
      microscopy. Therefore, our results support the comparative advantage that BDHQ
      has over PZQ.

PMID- 17435625
TI  - Aggressive angiomyxoma of the vulva in pregnancy: a case report and review of
      management options.

PMID- 17435626
TI  - Whatever happened to plausibility as the basis for clinical research and practice
      after EBM and CAM rushed in?

PMID- 17435627
TI  - It is time to extend the laboratory critical (panic) value system to include
      vital values.

PMID- 17435628
TI  - Case 15: when a stroke is not a stroke.

PMID- 17435629
TI  - Bupropion normalizes cognitive performance in patients with depression.

PMID- 17435630
TI  - Alcohol dependence patterns and their impact on New York City.
AB  - As a follow-up to a national survey by the Community Anti-Drug Coalitions of
      America (CADCA), an expert panel was convened to discuss local alcoholism data
      from New York, NY. The impact of alcoholism on the US economy is estimated at
      $185 billion annually. About 15% of New Yorkers drink alcohol excessively, with
      the highest percentage in Manhattan (22%). Over 135,000 New York City residents
      are admitted for alcohol treatment. Alcohol dependency is highest among whites
      (21%), followed by Latinos (14.8%) and African Americans (11%). Despite lower
      levels of excessive drinking, African-American and Latino New Yorkers are more
      likely than white New Yorkers to be hospitalized or die as a result of excessive
      drinking. The barriers to overcome are the lack of information on treatment
      options, the stigma of alcoholism, the lack of physician education, and a limited
      number of treatment facilities/personnel. Patients need behavioral counseling, a
      commitment to treatment, and compliance with medication if they are to succeed in
      treatment.

PMID- 17435631
TI  - Humanitarianism--a whole-cloth profession.

PMID- 17435632
TI  - Does Washington care about medical research?

PMID- 17435633
TI  - Possible role of Moringa oleifera Lam. root in epithelial ovarian cancer.

PMID- 17435634
TI  - Enterocolic fistula associated with an intestinal lymphoma.

PMID- 17435636
TI  - The marketplace can't give us the drug safety data we need.

PMID- 17435635
TI  - Executive summary of the African-American Initiative.
AB  - The roundtable discussion, "Managing Cardiovascular Disease in African Americans:
      Emerging Strategies for Optimizing Care, " was convened to review the evidence
      that supports best practices for the management of cardiovascular disease and its
      complications in African Americans. Treatment guidelines are reviewed, as is the
      clinical evidence supporting the use of diuretics, angiotensin-converting enzyme
      inhibitors, angiotensin receptor blockers, and beta-blockers. The ultimate goals
      of this work are to improve the understanding of the links among hypertension,
      diabetes, the metabolic syndrome, and cardiovascular disease, all of which
      disproportionately affect African Americans, and to increase physician awareness
      of the unique impact of these conditions in the often underserved African
      American population.

PMID- 17435637
TI  - Evaluation of possible gastrinoma.

PMID- 17435639
TI  - Biomedical entrepreneurship should be the fourth mission of all healthcare
      organizations.

PMID- 17435638
TI  - Paroxysmal hemidyskinesia related to a large thalamic cyst.

PMID- 17435640
TI  - Multiple biomarkers for the prediction of first major cardiovascular events and
      death: considerable costs and limited benefits.

PMID- 17435641
TI  - Small bowel bezoar in a patient with Noonan syndrome: report of a case.
AB  - BACKGROUND AND AIMS: Bezoars occur most commonly in patients with impaired
      gastrointestinal motility or a history of gastric surgery. Noonan syndrome is
      associated with gastrointestinal dysfunction and feeding difficulties in
      children. We report the case of a 64-year-old man with Noonan syndrome who was
      admitted to the hospital with a small bowel obstruction. An emergency laparotomy
      was performed and the patient was found to have a phytobezoar of the ileum that
      had caused edema of the intestinal wall resulting in the obstruction.
      METHODS/RESULTS: A review of the literature was performed with PubMed using the
      keywords "Noonan syndrome, " "bezoars, " and "phytobezoar. " Although problems
      with gastrointestinal motility in Noonan syndrome appear to improve with age, it
      is conceivable that in this case, abnormal gastrointestinal motility may have
      predisposed the patient to this condition. CONCLUSION: Bezoars are an uncommon
      but notable cause of small bowel obstruction. This is the first case of a bezoar
      in a patient with Noonan syndrome reported in the English literature.

PMID- 17435642
TI  - California and universal health coverage.

PMID- 17435643
TI  - The biopsychosocial information model: the new disease paradigm.

PMID- 17435645
TI  - Pay, pride, and public purpose: why America's doctors should support universal
      healthcare.
AB  - Discussion of universal healthcare is nothing new for US politicians or among
      reform advocates, policy experts, or the general public. Physicians, however,
      have been minor voices in the discussion. Their relative silence has been
      detrimental both to the public and to physicians themselves. We pose 3 arguments
      as to why physicians should support universal access grounded in medicine's own
      self-interest, arguments that are largely ignored in the current debate. These
      are: (1) the need for paying patients, (2) the need for a sense of self-esteem
      rooted in professionalism rather than commercialism, and (3) the urgency to
      affirm a public purpose for medicine by promoting the nation's health through
      universal care. Who has a stake in universal healthcare? Some groups, such as
      those lacking insurance, are obviously at risk and have a keen interest. Others,
      such as insured workers, have a less obvious but demonstrable concern. Arguments
      that urge adoption of an inclusive system typically focus on "healthcare horror
      stories" designed to evoke sympathy for the unfortunate persons whose lives are
      forever changed by unmet health needs or unpaid health bills. Our focus is
      different. We ask, regarding universal healthcare, "What's in it for physicians?"
      While the active support of doctors may not be a sufficient force to change the
      US system, it is probably a necessary one. At a minimum, universal coverage will
      be far less likely if physicians are opposed to it. Our aim here is to explore
      and discuss some of the reasons that should motivate active physician involvement
      in a more just and equitable system. We will discuss 3 reasons in particular.
      They are: (1) the need for paying patients; (2) the need to take pride in what
      one does--that is, the need to be nurtured by recognition of skillful
      professional performance in medical work, and not just rewarded monetarily; and
      (3) the importance of embracing a public purpose for medicine and thus engaging
      the trust and esteem of the population. We will examine each of these in turn,
      but first we will discuss briefly the other constituencies for universal
      coverage, since their reasons for supporting an inclusive system are often shared
      by doctors.

PMID- 17435644
TI  - Are various Babesia species a missed cause for hypereosinophilia? A follow-up on
      the first reported case of imatinib mesylate for idiopathic hypereosinophilia.
AB  - INTRODUCTION: In 2001 we reported the first case of use of imatinib mesylate
      (Gleevec) for treatment of idiopathic hypereosinophilia syndrome (HES). These
      findings have been replicated in some patients with HES. After 1 year of taking
      imatinib, the patient stopped this medication, and during the last 5 years the
      patient has not experienced a relapse. He has, however, recently been diagnosed
      with babesiosis. This new diagnosis might relate to his HES. METHODS: After 6
      years we decided to follow up on this patient's treatment. We interviewed the
      patient, his son, his aunt, and 2 consulting physicians and also reviewed
      relevant laboratory results to determine whether his HES had returned and whether
      his residual morbidity had changed. RESULTS: The patient has had no relapse of
      HES and his eosinophil counts have remained low-normal. He was recently diagnosed
      with babesiosis, and was prescribed atovaquone and azithromycin with a
      significant decrease in morbidity. His eosinophil cationic protein levels have
      also fallen to low-normal since starting atovaquone and azithromycin. DISCUSSION:
      New Babesia species are emerging as human infections. Most do not have available
      antibody or polymerase chain reaction diagnostic testing at this time. Manual
      differential examinations are of variable utility due to low numbers of infected
      red blood cells, suboptimal technique, and limited experience. Therefore, a
      diagnosis might need to be empirical at times, and should be based on signs and
      symptoms. CONCLUSION: The patient has not relapsed in the 5 years that he has not
      been taking imatinib. Babesiosis should be added to the many possible causes of
      HES. It is unknown how often babesiosis causes HES as well as what percentage of
      HES patients have babesiosis.

PMID- 17435646
TI  - Healthcare systems and motivation.
AB  - Despite the fact that most American physicians, at least until around the 1970s,
      stood in the way of developing a universal healthcare system, most are generally
      not happy with the current state of healthcare--or its lack thereof--today. The
      primary reasons for this general unhappiness are that insurance companies and
      managed care have successfully conspired to remove much of the physician's
      autonomy (via imposed time constraints, burdensome paperwork, the time-consuming
      chore of having to defend going against stringent treatment algorithms that are
      often inappropriate for some patients) and the satisfaction of knowing their
      patients. Few physicians in managed care organizations (MCOs) are able to
      practice without constant and blindly algorithmic interference concerning the
      diagnostic tests and therapeutic interventions they order. As copayments have
      increased, they often find that patients, even though "covered," cannot afford
      the therapy they deem necessary. While physicians expect to earn sufficient to
      pay back their not insignificant educational debts, provide their children with
      help through college, and assure retirements sufficient for themselves and their
      spouses, these should not be considered unreasonable expectations. Most
      physicians today do favor universal healthcare -- to the point of having included
      such language in their various professional codes of ethics (which, perversely
      enough, bioethicists as a group have failed to do). Contrary to the claims of our
      colleagues, Altom and Churchill, physicians seem to be genuinely frustrated as to
      what else they can do to change the current inequitable system.

PMID- 17435647
TI  - Reaffirming the public good.

PMID- 17435648
TI  - Evolution of a pulmonary insulin delivery system (Exubera) for patients with
      diabetes.
AB  - Many patients with diabetes fail to meet recommended glycemic goals regardless of
      the recognition of optimal glycemic control as a key component for improving
      clinical outcomes and quality of life in patients with diabetes. Patient- and
      physician-related barriers to the adoption of insulin therapy include fear and
      anxiety about injecting insulin, concerns about side effects, and personal health
      beliefs in regard to the use of insulin. There is an unmet need for an
      alternative insulin therapy that provides optimal glycemic control, is well
      tolerated, and improves patient adherence. Of the several inhaled insulin devices
      that are in various stages of development, the Exubera (INH) formulation is the
      first to be approved for use in the United States and in Europe. Exubera is a
      novel, rapid-acting inhaled human insulin formulation that has been developed for
      prandial insulin use. Clinical studies have shown that INH consistently improves
      glycemic control, in combination with longer-acting subcutaneous (SC) insulin
      regimens in patients with type 1 or type 2 diabetes, or is used to supplement or
      replace oral antidiabetic therapy in patients with type 2 diabetes. INH has
      demonstrated long-term safety and tolerability, with a risk for hypoglycemia
      similar to that of SC insulin, and no clinically meaningful changes in pulmonary
      function have been noted with its use. Patients treated with INH in clinical
      studies reported high levels of satisfaction with treatment, and many patients
      with diabetes choose inhaled insulin when it is offered as a treatment option.
      Taken together, these findings suggest that INH represents an important new
      development in the treatment of diabetes that may improve glycemic control in
      many patients with diabetes.

PMID- 17435649
TI  - High prevalence of overweight and obesity in homeless Baltimore children and
      their caregivers: a pilot study.
AB  - CONTEXT: In the past, nutritional deficiencies were common among homeless
      families. Because obesity is currently a major public health issue in the United
      States, it is possible that obesity has supplanted nutritional deficiencies as
      the "new malnutrition" of the homeless. OBJECTIVE: To perform a pilot study to
      determine the nutritional status of homeless caregivers and their children in the
      Baltimore City, Maryland. DESIGN: Determination of weight, height, and body mass
      index (BMI) (weight in kg/height in m2) of all subjects and correlation with
      demographic variables. SETTING: Six homeless shelters and transitional houses in
      Baltimore City. PATIENTS: Thirty-one caregivers and 60 children. MAIN OUTCOME
      MEASURES: Relationship between caregiver BMI and child BMI and comparison of our
      data to National Health and Nutrition Examination Survey (NHANES) norms. RESULTS:
      Forty-two percent of the children (25 of 60) had a BMI-for-age classifying them
      as at risk for overweight (18%) or overweight (23%). None were underweight. One
      hundred percent of girls and 88% of boys under age 7 years were in the normal
      range for BMI. There were no caregivers in the underweight range for BMI. Seventy
      seven percent were either overweight (26%) or obese (51%). When the weight
      categories of the largely African-American homeless Baltimore caregivers and
      their children were compared with national data from NHANES 1999-2002 for both
      African-American poor and nonpoor adult females and children, the Baltimore
      subjects had the lowest proportion in the healthy range and the highest
      proportion in the obese (adults) and overweight (children) categories. Caregiver
      BMI correlated with child BMI: r = 0.43, P = .0002. CONCLUSION: Our data suggest
      that overweight and obesity are the major forms of malnutrition in homeless
      families.

PMID- 17435650
TI  - How should you reference articles from MedGenMed, being that it is an exclusively
      online medical journal?

PMID- 17435651
TI  - What you don't know can hurt your patients.

PMID- 17435652
TI  - White coat hypertension: relevance to clinical and emergency medical services
      personnel.
AB  - CONTEXT: White-coat hypertension (WCHT) is a relatively unexplored cause of
      elevated blood pressure readings in the clinic and in prehospital emergency
      medical services (EMS) settings. OBJECTIVE: The purpose is to summarize WCHT in
      the clinical office setting and speculate on its relevance in the prehospital
      setting. This review emphasizes the etiology, diagnosis, prognosis, and
      application of WCHT in both the clinical and prehospital settings. DATA SOURCES:
      A systematic literature review was undertaken with the Medline PubMed database,
      UpToDate, and Web of Science. The following search queries were used:
      "prehospital WCHT, " " prehospital white coat hypertension, " "EMS WCHT, " "
      emergency medical services white coat hypertension, " " ambulatory WCHT, " "
      ambulatory white coat hypertension, " " labile HTN, " " labile hypertension, " "
      variable HTN, " and " variable hypertension " limited to 1980-July 2006. Only
      human studies published in English were included. STUDY SELECTION: The reviews
      yielded 233 articles initially, which were narrowed down to those mentioned
      herein by direct relevance to either the observed WCHT effect in the clinic or
      the prehospital setting. DATA SYNTHESIS: WCHT has not been applied or explored in
      the prehospital setting as of yet, and thus all data were shown to be related to
      clinical WCHT. It was found that WCHT may not be simply a benign entity but
      rather part of a continuum in the development of true essential hypertension. It
      was found that WCHT patients, when followed, had higher morbidity than non-WCHT
      patients but less morbidity than established essential hypertensive patients.
      CONCLUSIONS: WCHT may be a significant step toward the evolution into full-blown
      hypertension. For many populations, routine access to a healthcare provider is
      not possible, and thus their only interaction with healthcare providers may be in
      the prehospital EMS setting. On the basis of findings of true organic morbidity
      in WCHT, it comes to reason that contact with patients in the setting should be
      thorough--including urging follow-up for those whose blood pressure is found to
      be elevated in the presence of healthcare professionals.

PMID- 17435653
TI  - Healthcare and the hospital chaplain.
AB  - Many chaplains and most chaplaincy programs in the United States--with
      encouragement from their accrediting organization, the Association for Clinical
      Pastoral Education (ACPE)--have begun to assume a more proactive stance toward
      patients, healthcare professionals, and healthcare facilities. Some chaplains and
      chaplaincy programs have begun to engage in activities that have ranged from
      initiating conversations with and perusing the medical records of patients who
      have not requested their services to proposing that they be permitted to do
      "spiritual assessments" on patients--in some instances whether these patients
      have been explicitly informed and have agreed to this beforehand. Moreover, many
      chaplains and chaplaincy programs have begun to assume that chaplains are full
      fledged members of the healthcare team, complete with access to patients' medical
      records both to gather information and to make notations of their own. It would
      appear that such novel activities are being justified by a questionable set of
      claims and assumptions that includes: (1) the claim that chaplains have a
      spiritual--as opposed to purely religious--expertise that entitles them to
      interact with patients and/or significant others (even those who have not
      requested a chaplain)--presumably without in the least compromising patient
      autonomy or the confidentiality of the patient/healthcare professional
      relationship; (2) the assumption that the terms "spirituality" and "religiosity"
      mutually entail one another; (3) the claim that the Joint Commission on the
      Accreditation of Healthcare Organizations (JCAHO) mandates "spiritual
      assessments" (which it does not); (4) the assumption that chaplains are full
      fledged members of the healthcare team; and (5) the claim that chaplains must,
      therefore, be permitted access to patients and patients' medical records both to
      gather information and to make notations of their own. We consider such claims
      and assumptions disquieting, and suggest that it is high time we revisit the
      terms "chaplaincy," "healthcare professional," and "member of the healthcare
      team" in reassessing what our professional commitments to respect and protect the
      bio-psycho-social integrity of patients require.

PMID- 17435654
TI  - Carotid screening guidelines--overvalued.

PMID- 17435655
TI  - Extraintestinal manifestations of inflammatory bowel disease: focus on the
      musculoskeletal, dermatologic, and ocular manifestations.

PMID- 17435657
TI  - Resource allocation in healthcare: implications of models of medicine as a
      profession.
AB  - For decades, the problem of how to allocate healthcare resources in a just and
      equitable fashion has been the subject of concerted discussion and analysis, yet
      the issue has stubbornly resisted resolution. This article suggests that a major
      reason for this is that the discussion has focused exclusively on the nature and
      status of the material resources, and that the nature and role of the medical
      profession have been entirely ignored. Because physicians are gatekeepers to
      healthcare resources, their role in allocation is central from a process
      perspective. This article identifies 3 distinct interpretations of the nature of
      medicine, shows how each mandates a different method of allocation, and argues
      that unless an appropriate model of medicine is developed that acknowledges the
      valid points contained in each of the 3 approaches, the allocation problem will
      remain unsolvable.

PMID- 17435656
TI  - About intercessory prayer: the scientific study of miracles.

PMID- 17435658
TI  - HIV care at a crossroads: the emerging crisis in the US HIV epidemic.

PMID- 17435659
TI  - To be a great physician, you must understand the whole story.

PMID- 17435661
TI  - Improving laboratory testing to save lives in resource-limited settings, with a
      particular focus on HIV/AIDS: humanitarian efforts by the ASCP.

PMID- 17435660
TI  - Dietary factors in the modulation of inflammatory bowel disease activity.
AB  - CONTEXT: As patients look to complementary therapies for management of their
      diseases, it is important that the physician know the effectiveness and/or lack
      of effectiveness of a variety of dietary approaches/interventions. Although the
      pathogenesis of the inflammatory bowel diseases (ulcerative colitis and Crohn's
      disease) is not fully understood, many suspect that diet and various dietary
      factors may play a modulating role in the disease process. EVIDENCE ACQUISITION:
      The purpose of this article is to present some of what is known about various
      dietary/nutritional factors in inflammatory bowel disease, with inclusion of
      evidence from various studies regarding their putative effect. MedLINE was
      searched (1965-present) using combinations of the following search terms: diet,
      inflammatory bowel disease, Crohn's disease, and ulcerative colitis.
      Additionally, references of the articles obtained were searched to identify
      further potential sources of information. EVIDENCE SYNTHESIS: While much
      information is available regarding various dietary interventions/supplements in
      regard to inflammatory bowel disease, the lack of controlled trials limits broad
      applicability. Probiotics are one of the few interventions with promising results
      and controlled trials. CONCLUSION: While there are many potential and promising
      dietary factors that may play a role in the modulation of inflammatory bowel
      disease, it is prudent to await further controlled studies before broad
      application/physician recommendation in the noted patient population.

PMID- 17435662
TI  - Plasma testosterone, dehydroepiandrosterone sulfate, and cortisol in female
      patients with Huntington's disease.
AB  - OBJECTIVE: The neuronal loss in several brain regions that characterize the
      progression of Huntington's disease (HD), is expected to influence the activities
      of hypothalamus-adrenal and hypothalamus-gonadal axes, and the changes may relate
      to common features of the disease, like depression and dementia. While in male HD
      patients low plasma testosterone levels have been reported, information on female
      patients is lacking. METHODS: We assessed the plasma levels of the androgens
      total testosterone (TT) and dehydroepiandrosterone sulfate (DHEAS), as well as of
      cortisol in 41 female patients with HD, confirmed by determination of the CAG
      repeat number in the IT-15 gene, and searched for associations to the disease
      symptomatology. We also included a group of 18 females with expanded CAG repeat
      number in the HD gene (subjects at risk), and a group of 66 age-matched healthy
      females. Hormone levels of the pre- and post-menopausal subgroups were also
      compared separately. RESULTS: Significant negative correlations to age were found
      for TT and DHEAS in both control (age range 20-71 years) and patient (age range
      26 to 78 years) groups, and the calculated decline per year was around 1% for TT
      and 1.5% for DHEAS. There were no significant differences in hormone levels among
      patients, subjects at risk and controls, either in premenopausal or in
      postmenopausal state. The subgroup of patients with depression in their
      symptomatology had significantly lower TT and DHEAS levels compared to patients
      without depression, or to controls. CONCLUSIONS: While TT and DHEAS seem to
      decline with age in female patients with HD to the same extend as for healthy
      females, the presence of depression, but not dementia, in their symptomatology,
      is connected to lower ovary-adrenal androgen levels.

PMID- 17435663
TI  - In vitro assessment of curcumin against murine neuroblastoma cells.
AB  - OBJECTIVE: Neuroblastoma (NB) is a well-known malignant disease in infants, which
      comprises 10% of childhood malignancies. Despite recent advances in understanding
      the neuro-oncology, NB still accounts for more death in childhood than any other
      cancer. Research in childhood tumors should not only be focused on the malignant
      signatures of cancer cells but also novel drug prototypes using phytochemicals.
      The present study was aimed to determine the role of curcumin against murine
      neuroblastoma cell line (N2a). METHODS: The in vitro assessment of curcumin
      against was made in N2a cell line in a dose-dependent manner (group I (control)
      and group II - IX (10 microM-80 microM). The efficacy of the drug was evaluated
      by estimating the levels of protein bound carbohydrates, glycoprotein, genomic
      DNA, total RNA levels, and inhibition of MMP-9 were studied. The gap junctional
      communication in the cells was also assessed. RESULTS: The levels of protein
      bound carbohydrates, DNA, RNA levels, glycoprotein were found to be altered on
      drug supplementation in NB cells. Inhibition of MMP-9 in curcumin-supplemented
      N2a cells was revealed by zymographic analysis. Assessment of Lucifer yellow dye
      uptake in curcumin-supplemented N2a cells showed the up-regulation of GJIC.
      CONCLUSIONS: These observations suggest that the curcumin, the active principle
      of curcuma longa, could be developed into an effective chemo preventive and
      chemotherapeutic agent. This selected concentration range needs further studies
      at molecular level, for conforming its role and its action against uncontrolled
      proliferation of NB.

PMID- 17435664
TI  - The change of blood Pb levels of basketball players after strenuous exercise.
AB  - This study is related to the investigation of the Pb levels in blood of the 12
      healthy University male basketball players before and after a strenuous training
      session by the use of square wave anodic stripping voltammetry. Although the
      results do not show acute lead intoxication it is obvious that blood lead levels
      show significant increase after training sessions. The average increase in blood
      lead levels is 297%. This increase is largely due to increased respiration rate
      during the training period.

PMID- 17435665
TI  - Serum levels of sex hormones in men with acute myocardial infarction.
AB  - OBJECTIVE: To compare the serum levels of total testosterone(TT), free
      testosterone (FT), estradiol, sex hormone binding globulin (SHBG), and
      androstenedione (AS) in patients with acute myocardial infarction (AMI) at the
      time of hospitalization, patients with old myocardial infarction (OMI), and
      patients with normal coronary arteries (NC) admitted for diagnostic coronary
      angiography. METHODS: Serum sex hormones and lipid profile were measured in 79
      male patients; 30 patients with AMI, 21 patient with OMI and 28 patients with NC.
      Ages ranged from 33-68 years. Androstenedione, estrogen, both total and free
      testosterone levels were quantified using coat-a-count radioimmunoassay kits. Sex
      hormone binding globulin was analyzed using immunoradiometric assay (IRMA)-count
      kits. RESULTS: The levels of serum estradiol in the AMI were significantly higher
      and serum levels of TT, FT, and SHBG were significantly lower in AMI than in OMI
      and NC but there was no difference found for the levels of AS in all groups.
      Estradiol level was also higher in OMI than in control group but no significant
      changes found for other sex hormones in OMI and control group. Also triglyceride,
      high density and low density lipoprotein in AMI were significantly different from
      that in OMI and control groups. CONCLUSIONS: Serum estradiol and low density
      lipoprotein levels are increased but TT, FT and SHBG levels are decreased in men
      with AMI compared with patients with NC.

PMID- 17435666
TI  - Ultrasonographic assessment of fetal nuchal translucency (NT) at 11th and 14th
      week of gestation--Polish multicentre study.
AB  - THE AIMS OF THE STUDY WERE: To evaluate range and median values of NT in a large,
      unselected Polish population; to determine the value of the 95th percentile and
      the median values for NT for given weeks of late 1st trimester pregnancy and to
      determine the level of chromosomal aberration risk corresponding to the values of
      the 95th percentile in the examined groups; to examine the possible correlation
      between CRL, NT width as well as the mother's age with the risk of the most
      frequent chromosomal aberrations. MATERIAL & METHODS: We have retrospective
      analyzed 7,866 pregnant women. All fetuses of this women had NT measurement
      performed, as well as CRL and assessed of the most frequent chromosomal
      abnormalities. The group of pregnant women was divided into 2 subgroups: until
      and above 35 years old. All population group was divided into 3 subgroups
      depending on gestational age (11, 12 and above 13th weeks of gestation). RESULTS:
      The median of NT in all population group was 1.5 mm and 95th percentile was 2.4
      mm, whilst in group with low risk median of NT and 95th percentile were the same
      and in group with high risk of chromosomal abnormalities respectively 1.5 mm and
      2.5 mm. There were strong correlations between maternal age and the risk of most
      frequent chromosomal abnormalities from NT. CONCLUSIONS: The obtained results of
      median values and the 95th percentiles of NT in the examined group and the age
      groups under 35 and 35 plus are similar to these quoted by FMF. The risk levels
      of trisomy of 21st chromosome were similar to the reference values used by FMF.
      With gestational age, NT value increases in a non-linear way, therefore it is
      incorrect to use the term "a normal value" for NT, therefore, only the risk level
      calculated with the dedicated software using NT and CRL measurements with
      maternal age should be stated.

PMID- 17435667
TI  - Evaluation of erythropoietin effects on cerebral ischemia in rats.
AB  - OBJECTIVE: Majority of severe disabilities in adults are caused by stroke. The
      aim of our study is to learn the effects of erythropoietin (EPO), on infarct size
      in cerebral ischemia and to determine neurological behavioral scores and
      histopathological evaluation. MATERIAL & METHODS: In this study 30 adult Sprague
      Dawney rats were used. Cerebral ischemia was constituted by intraluminal filament
      method with a 4-0-nylon suture. Reperfusion was started after two hours of middle
      cerebral artery occlusion. The rats were randomly divided into two groups as
      follow: control and EPO groups. Saline 0.9% (0.5 ml/kg) and EPO (5 000 U/kg) was
      administered intraperitoneally in the groups. Three coronal slices in two
      millimeters thickness were obtained from cerebrum, cerebellum and brain stem, and
      were stained with a 2% solution of triphenyltetrazolium chloride. Transparent
      sheets were placed over each section and the areas of the brain and infarct were
      measured. The neurological scores were determined at 24th, 48th and 72nd hours
      after reperfusion. RESULTS: Percent of ischemic area (%) in cerebrum, cerebellum
      and brain stem level in EPO groups were less than those of control group
      (p<0.0001). In addition, we determined that EPO group was better than controls of
      neurologic score and histopathologically after cerebral ischemia. CONCLUSIONS: We
      concluded that EPO may decrease ischemic area in experimental cerebral ischemia
      in rats and it seems that EPO may be beneficial.

PMID- 17435668
TI  - PACAP 38 inhibits adiponectin release.
AB  - BACKGROUND: Pituitary adenylate cyclase activating peptide (PACAP 38) is a
      neuropeptide with anti-inflammatory activity. Vasoactive intestinal peptide
      (VIP)/PACAP receptors are found in immune cells, endocrine glands and also in
      adipose tissue. Adiponectin is an adipocyte-derived protein hormone which
      possesses anti-inflammatory, antidiabetic and antiatherogenic properties. The aim
      of this study was to examine the influence of PACAP 38 on adiponectin release in
      basal conditions and during lipopolysaccharide (LPS)-induced acute inflammation.
      METHODS: Male Wistar-Kyoto rats were divided into four groups which received
      intraperitoneal injections of 0.9% NaCl, LPS, PACAP 38 or LPS+PACAP 38,
      respectively. Serum adiponectin concentrations were measured using an ELISA test.
      RESULTS: LPS administration did not change adiponectin concentration; however,
      PACAP 38 administered alone decreased serum adiponectin concentration after 2 h
      (p<0.05) and 4 h (p<0.01). In the group that received LPS+PACAP38, compared with
      LPS alone, no difference in adiponectin concentration was observed. CONCLUSIONS:
      We conclude that PACAP 38 may directly modulate adiponectin secretion by
      adipocytes in basal conditions.

PMID- 17435669
TI  - Diabetes induces changes in melatonin concentrations in peripheral tissues of
      rat.
AB  - OBJECTIVE: Exogenous melatonin was found to protect target organs under
      conditions of diabetes mellitus, however, concentrations of the hormone in
      peripheral tissues have not been determined. Therefore the aim of the present
      study was to measure the daily profile of melatonin levels in the pineal gland,
      plasma, pancreas, kidney, spleen, duodenum and colon of control and diabetic
      rats. MATERIAL & METHODS: Diabetes was induced by a single injection of
      streptozotocin (STZ, 65 mg/kg of body weight) and samples were collected over a
      24 hr cycle on day 17 after STZ treatment. Melatonin and corticosterone levels
      were measured directly in plasma and after extraction in the pineal gland and
      peripheral organs (pancreas, kidney, spleen, duodenum and colon). RESULTS: A
      significant daily rhythm of melatonin concentrations was found not only in the
      pineal gland and plasma but also in the pancreas, kidney, spleen and duodenum.
      The daily pattern of melatonin levels in the colon was arrhythmic without a
      characteristic night-time increase of hormone concentration. Experimentally
      induced diabetes resulted in lower melatonin levels in the pancreas, kidney and
      duodenum as compared to control. No differences between STZ-treated and control
      rats were found in the spleen and colon. Plasma corticosterone levels were
      enhanced in diabetic rats in comparison with controls and the daily profile was
      not rhythmic. CONCLUSION: Our data suggest that the lower amplitude of melatonin
      rhythm in target organs induced by experimental diabetes can contribute to
      desynchronization of daily rhythms and can lower the antioxidative capacity of
      tissues.

PMID- 17435670
TI  - Brain derived neurotrophic factor gene Val66Met and -270C/T polymorphisms and
      personality traits predisposing to anorexia nervosa.
AB  - OBJECTIVES: Polymorphisms in BDNF gene has been proposed, as susceptibility loci
      for stress-related psychiatric disorders. Several lines of molecular and
      biochemical evidence point to the role of BDNF in anorexia nervosa (AN).
      Personality traits may constitute the intermediate phenotypes between genes and
      vulnerability to AN. METHODS: BDNF Val66Met and -270C/T polymorphisms were
      genotyped in 149 patients with AN and 100 healthy control females. Temperamental
      traits in all subjects were measured with Temperament and Character Inventory.
      First in case-control analysis, we assessed, if analyzed genotypes confer risk
      for AN. Next, the association of BDNF gene variants with personality dimensions
      in patients and control subjects was analyzed. RESULTS: No significant
      differences between patients with anorexia nervosa and controls in frequency of
      genotypes and alleles were observed. AN patients with Met allele showed higher
      Harm avoidance (Anova F=4.70; p=0.03) than Val/Val homozygotes. AN patients, who
      carried the T allele of BDNF -270C/T polymorphism showed higher Persistence
      (Anova F=4.04; p<0.05) and Harm avoidance (Anova F=7.93; p=0.006) than C/C
      homozygotes, however after correction for multiple testing only the latter
      association remained statistically significant. No significant relationship
      between Val/Met 66 genotype and -270C/T genotype with personality was observed in
      healthy females. CONCLUSIONS: These results may suggest, that BDNF -270 C/T
      polymorphism may influence the personality trait associated with higher risk of
      AN.

PMID- 17435671
TI  - Pericardial effusion due to hypothyroidism in Down syndrome: report of four
      cases.
AB  - Pericardial effusion may be the first sign of congenital or acquired
      hypothyroidism and will completely resolve after thyroxin therapy. Hypothyroidism
      is more common in Down syndrome population than normal population. In this report
      we present four infants with Down syndrome who have pericardial effusion due to
      congenital hypothyroidism. All of these children with Down syndrome were admitted
      to our clinic with pericardial effusion. Pericardial effusion was completely
      resolved with thyroxin therapy without pericardiosentesis. Any child with Down
      syndrome who present with dyspnea and cardiomegaly should be suspected of having
      pericardial effusion due to hypothyroidism and echocardiography examination
      should be performed immediately. Pericardial effusion due to hypothyroidism will
      completely resolve with L-thyroxin therapy without pericardiosentesis. In
      conclusion, since a delayed diagnosis of hypothyroidism is likely and may favor
      the development of massive pericardial effusion and because of the difficult
      diagnosis of the hypothyroidism in Down syndrome, periodic follow-up of thyroid
      function tests are important.

PMID- 17435672
TI  - Comparison of tubal patency assessment during microlaparoscopy and laparoscopy,
      and its compatibility with previous histerosalpingography results.
AB  - OBJECTIVES: The aim of the study was to compare tubal patency assessment during
      microlaparoscopy and laparoscopy and its compatibility with previously performed
      histerosalpingography (HSG). MATERIAL & METHODS: Endoscopic evaluation of tubal
      patency was performed on 135 women, aged 30-39 (microlaparoscopy in 65 cases,
      laparoscopy in 70). In the group of 42 patients qualified for endoscopy,
      histerosalpingography was carried out in the past. The duration of tubal patency
      assessment was counted from the moment of the salpingograph placement, with
      trocars already introduced into the peritoneal cavity. RESULTS: The mean duration
      of tubal patency evaluation during laparoscopy was 5'45"+/-39 and during
      microlaparoscopy - 7'30"+/-49". The results of the examination were afterwards
      compared with the results of previously performed HSG. Their sensitivity,
      specificity, compatibility and positive and negative predictive values were
      calculated. The sensitivity and specificity of microlaparoscopy in tubal patency
      assessment were 81% and 100%, respectively; its positive predictive value -100%
      and negative -96%. As to laparoscopy, the values were established at 90%, 100%,
      100% and 98.4%, respectively. CONCLUSIONS: Tubal patency assessment during
      microlaparoscopy and laparoscopy is characterized by similar sensitivity and
      specificity. Although the mean duration of microlaparoscopy is significantly
      longer, the difference in time is of no practical implication.

PMID- 17435673
TI  - Effects of moderate ethanol drinking on the GH and cortisol responses to physical
      exercise.
AB  - OBJECTIVE: To evaluate the effects of moderate amounts of ethanol on the GH and
      cortisol responses to physical exercise. METHODS: Ten normal men underwent three
      bicycle ergometer tests. Test were carried out in basal conditions (control test)
      or after drinking 0.5 or 0.75 g/kg BW ethanol. Tests lasted 15 min in all
      subjects; the workload was increased at 3 min intervals from time 0 until
      exhaustion. Non-endocrine physiological parameters (NEPP), such as heart rate,
      blood pressure, ventilation, frequency of breathing, tidal volume, oxygen
      consumption, carbon oxide production and respiratory exchange ratio were measured
      from time 0 until exhaustion. Serum GH and cortisol levels were evaluated in
      blood samples taken at 5-10 min intervals over a 50 min period from time 0.
      RESULTS: Neither basal values, nor exercise-induced changes in NEPP were altered
      by ethanol drinking. Both GH and cortisol levels significantly rose during the
      exercise control test. The hormonal responses did not change after 0.5 g/kg BW
      ethanol, whereas they significantly decreased after 0.75 g/kg BW ethanol.
      CONCLUSIONS: Modification of the GH and cortisol responses to exercise represents
      an "endocrine window" of the effects that even moderate ethanol drinking produces
      in the CNS. The data show that 0.75 g/kg BW ethanol is the minimal amount
      producing significant inhibitory effects on the GH and cortisol responses to
      physical exercise. In view of the important roles played by GH and cortisol
      during physical activity, even moderate ethanol drinking must be avoided before
      sport.

PMID- 17435675
TI  - Two-month stability of hyperbolic discount rates for delayed monetary gains in
      abstinent inpatient alcoholics.
AB  - OBJECTIVES: Alcohol dependence has been associated with disrupted neuroendocrine
      systems, impulsivity in intertemporal choice (delay discounting). However, little
      is known regarding stability of discount rates in alcoholics. This study examined
      both differential stability (stability of individual differences) and absolute
      stability (stability of group mean) of hyperbolic discount rates for monetary
      gains in severe alcoholic inpatients (diagnosed with DSM-IV) over a 2-month
      period during abstinence. METHODS: We estimated male alcoholics' discount rates
      for delayed monetary rewards on the basis of their pattern of choices between
      smaller immediate rewards (1,100-8,000 yen) and larger, delayed rewards (2,500
      8,500 yen; at delays from 1 week to 6 months), two times at 2-month time-interval
      during hospitalized alcohol withdrawal. RESULTS: It was observed that the
      alcoholics' mean hyperbolic discount rates for gains had both differential and
      absolute stability over 2 months, although a slight non-significant decrease in
      the group mean of the discount rates was observed. CONCLUSIONS: The results
      indicate that abstinent alcoholic's discount rates are stable over a relatively
      long-term period. The usefulness of assessing discount rates of addicts in
      psychoneuroendocrinology and neuroeconomics of addiction is discussed.

PMID- 17435674
TI  - Slowly progressive voluntary-automatic dissociation of facial movements (Foix
      Chavany-Marie syndrome).
AB  - We describe a case of slowly developing Foix-Chavany-Marie syndrome associated
      with distinctive bilateral cortical atrophy of frontal lobes in a 59-year old
      woman. The neurophysiological mechanism and differential diagnosis concerning the
      unusually slow progression are discussed.

PMID- 17435676
TI  - Somatosensory evoked response and jaw opening reflex elicited by tooth pulp
      stimulation in awake freely moving rats.
AB  - OBJECTIVE: Investigation of pain and nociception refers to different models.
      Depending upon the intensity of stimulation, unmyelinated pulpal fibers or
      periodontal A-fibers can be stimulated producing a short or a long latency jaw
      opening reflex of the digastric muscle. This paper investigates the different
      components of the jaw opening reflex in addition to the correlation between
      afferent fibers involved in the cortical evoked response. DESIGN AND SETTING:
      Fifteen awake male rats were implanted with tooth pulp stimulation electrodes,
      digastric and cortical recording electrodes. Ten rats were submitted to
      recordings after a single tooth pulp stimulation, while five rats were using
      conditioning and test stimulation. Tooth pulp evoked potentials and digastric EMG
      were simultaneously recorded. A multiresolution denoising method was used for
      signal processing. RESULTS: Following tooth pulp stimulation, a cortical response
      was produced including the following peaks: P6.5 +/- 1.1, N11 +/- 1.2, P17 +/-
      1.2, P27 +/- 2.9, N53 +/- 7.5, P69 +/- 5.8, P88 +/- 13, N160 +/- 9.7, P204 +/-
      14.2. The distribution and amplitude of these peaks are correlated to the
      stimulation intensity (r=0.96, p<0.01). An interaction between the different
      components of the jaw opening reflex was identified on EMG, following a
      conditioning shock, where a cortical evoked response showed a P30 +/- 2.7 peak
      which was observed concurrently with the jaw opening long latency reflex.
      CONCLUSION: Our results identify the interaction between the different components
      of the jaw opening reflex and the correlation to the cortical evoked response.

PMID- 17435677
TI  - Epidemiological evidences from China assume that psychiatric-related diseases may
      be associated with Toxoplasma gondii infection.
AB  - In recent years, the effect of Toxoplasma gondii infection on psychiatric-related
      aspects has been increasingly recognized. T. gondii has a high affinity for brain
      tissue where tachyzoites may form tissue cysts and persist life long. In recent
      years, 15 serological surveys about T. gondii infection and psychiatric diseases
      have been carried out in different areas in China. Studies showed that the
      prevalence of antibodies against T. gondii in psychotic patients was much higher
      than in normal persons; statistically differences were significant. Studies also
      reported that raising cats or enjoying the habit of eating raw or under cooked
      meet were potential risk factors for the infection of T. gondii. The
      epidemiological and serological evidence support the hypothesis that some
      psychiatric diseases such as schizophrenia or mental retardation might be linked
      to T. gondii infection.

PMID- 17435678
TI  - Higher perceived dominance in Toxoplasma infected men--a new evidence for role of
      increased level of testosterone in toxoplasmosis-associated changes in human
      behavior.
AB  - Toxoplasma is parasite of cats that uses any warm-blooded animals as intermediate
      hosts. It is known to induce shifts in behavior, physiology and even morphology
      of its intermediate hosts, including humans. The lower second to fourth digit
      ratio (2D:4D ratio) in infected man and women, and higher height in infected man
      suggest that sex steroid hormones like testosterone could play a role in these
      shifts. Here, we searched for another indirect indication for a higher postnatal
      testosterone level, i.e. increased perceived dominance and masculinity in
      infected men. We showed portrait pictures of 89 male students of which 18 were
      Toxoplasma-infected to 109 female students. When we statistically corrected for
      age, men with latent toxoplasmosis were perceived as more dominant (p=0.009) and
      masculine (p=0.052). These results support the idea that the higher level of
      testosterone could be responsible for at least some of the toxoplasmosis
      associated shifts in human and animal behavior.

PMID- 17435679
TI  - Chaotic neural response during conflicting Stroop task reflects the level of
      serum cortisol in patients with unipolar depression.
AB  - OBJECTIVE: According to recent findings detecting a cognitive conflict is related
      to activation of anterior cingulate cortex (ACC) and central autonomic network.
      Several recent findings also suggest the hypothesis that the cognitive conflict
      is related to specific nonlinear chaotic changes of the neural signal. This
      conflict related activation elicits autonomic responses which can be assessed by
      psychophysiological measures such as heart rate variability calculated as beat to
      beat R-R intervals (RRI). METHOD: The present study used Stroop word-colour test
      as an experimental approach to psychophysiological study of cognitive conflict in
      connection with RRI measurement, assessment of serum cortisol and calculation of
      largest Lyapunov exponents in nonlinear data analysis of RRI time series in 30
      patients with unipolar depression. RESULTS: Significant correlation -0.45
      (p<0.01) between largest Lyapunov exponents during conflicting Stroop task and
      serum cortisol levels has been found. CONCLUSIONS: The study indicates that a
      defect of neural inhibition during conflicting Stroop task is closely related to
      decreased serum cortisol levels which probably reflect defense psychological
      mechanisms.

PMID- 17435680
TI  - Genetic background of carcinogenesis in the thyroid gland.
AB  - The process of carcinogenesis is permanently one of the most interesting and
      significant issues for researchers in different fields of medicine. Therefore, we
      attempted to bring closer the problem of neoplastic transformation in the thyroid
      gland. This article covers the latest data about genetic factors, involved in
      thyroid carcinogenesis. We have presented results of the most recent studies
      referred to molecular biology of thyroid neoplasms. We have demonstrated not only
      the genetic background of cancers, derived from the thyroid follicular cell, but
      also genetic aspects related to medullary thyroid carcinoma and some benign
      thyroid lesions. The review describes DNA methylation disturbances and the
      mutations in thyrotropin receptor and G protein genes. Furthermore, we introduce
      the results of studies performed at our laboratory, concerning mutations in the
      following protooncogenes: RAS, RET, Trk, MET, and BRAF. Also, we present our
      data, regarding the loss of heterozygosity (LOH) in the short arm of chromosome
      3. Additionally, we discuss overexpression of cyclin D1 gene in benign and
      malignant thyroid lesions. Previous studies performed at our laboratory indicate
      the role of IGF-I in the pathogenesis and invasiveness of thyroid cancers. The
      review indicates that progress in genetics of the thyroid cancer is extremely
      rapid.

PMID- 17435681
TI  - Psychobiology of dissociation and its clinical assessment.
AB  - OBJECTIVE: Dissociation is often defined as partial or total disconnection
      between memories of the past, awareness of identity and of immediate sensations,
      and control of bodily movements, often resulting from traumatic experiences,
      intolerable problems, or disturbed relationships. This type of reaction to a
      psychological and/or physical trauma has often various neurobiological
      consequences and its clinical assessment has received enormous interest in recent
      psychological and neuroscience research. METHODS: Psychometric parameters of the
      Czech version of the Dissociative Experiences Scale were tested from the
      viewpoints of internal consistency, validity and factor structure, using data
      from a sample of n=783 adults, divided into three groups (epilepsy n=243,
      depression n=357, norm n=183), average age 39 years, SD=13.5. RESULTS: Findings
      of this study demonstrated that reliability, validity and factor structure of the
      Czech version of the Dissociative Experiences Scale correspond to those of the
      original English version. CONCLUSIONS: The Czech version of the questionnaire may
      be considered a suitable tool for estimating subjectively experienced
      dissociative symptoms.

PMID- 17435682
TI  - Causes of poor outcome after cataract surgery in Satkhira district, Bangladesh.
AB  - AIMS: Recent data have raised concerns about visual outcome following cataract
      surgery. The aim of this study was to assess the frequency and causes of poor and
      borderline outcome after cataract surgery in a population-based case series in
      Satkhira district, Bangladesh. METHODS: A population-based case series was
      conducted within a population-based cluster survey of people aged over 50 years
      in Satkhira district where 4868 people underwent visual acuity (VA) screening.
      Eyes operated for cataract with VA<6/18 were examined in detail by an
      ophthalmologist, including a full history and dilated fundoscopy, to determine
      the cause of the visual outcome. RESULTS: Cataract surgery was performed on 213
      eyes. Outcome was good (VA>6/18) for 128 eyes (60.1%), borderline (VA<6/18 to
      6/60) for 35 eyes (16.4%), and poor (VA<6/60) for 50 eyes (23.5%) with available
      correction. Borderline and poor outcomes were most commonly due to lack of
      spectacles (25.8%), poor selection (33.8%), or surgical complications (30.6%).
      Surgical sequelae, namely posterior capsule opacification, was a less common
      cause of poor or borderline outcome (9.7%). CONCLUSIONS: Quality of surgical
      outcomes is of concern in Satkhira district. Increased emphasis on selection of
      subjects for surgery, provision of spectacles, and monitoring of surgery may
      improve outcomes.

PMID- 17435683
TI  - Functional outcome and patient preferences following combined phaco-vitrectomy
      for macular hole without prone posturing.
AB  - BACKGROUND: Macular hole surgery varies widely regarding the duration of gas
      tamponade, the use of patient posturing post-operatively, and whether or not
      cataract extraction is undertaken at the same time. AIM: To analyse anatomical
      and functional success rate following macular hole surgery and to examine patient
      preferences regarding posturing and length of gas tamponade. MATERIALS AND
      METHODS: Study design. Prospective, interventional and non-comparative case
      series. PARTICIPANTS: Thirty patients with stage III and IV full-thickness
      macular hole who underwent macular hole repair during the period April 2005
      January 2006.Intervention. All eyes underwent a standard three-port pars plana
      vitrectomy, removal of posterior vitreous, internal limiting membrane (ILM) peel,
      C3F8 gas tamponade, and cataract extraction with IOL implantation. Patients did
      not posture post-operatively.Outcome measures. Post-operative anatomic results,
      visual acuity, complications, patient preferences regarding surgical protocol,
      and subjective improvement in visual function. RESULTS: Patients were followed up
      post-operatively for 6 months. Primary anatomical hole closure was achieved in
      96.7% eyes. Visual acuity improved in 83.8% patients. Two patients had raised
      intraocular pressure following surgery. A total of 96.9% of patients were happy
      with no posturing and a 2-month gas bubble. CONCLUSIONS: There is a high rate of
      anatomical and functional success in patients undergoing macular hole surgery
      without prone posturing. In our study, most patients preferred long-acting gas
      tamponade with no posturing over the option of posturing with short-acting gas
      tamponade.

PMID- 17435684
TI  - Position of myopic iris-claw phakic intraocular lens by Scheimpflug photography
      and ultrasound biomicroscopy.
AB  - PURPOSE: To evaluate the position of iris-claw phakic intraocular lens (ICPIOL)
      in highly myopic eyes by Scheimpflug photography (SP) and ultrasound
      biomicroscopy (UBM). METHODS: Nine eyes of five patients aged 31+/-10 years with
      average spherical equivalent of -16.04+/-5.46 D (range -7.88 to - 22.88 D) were
      enrolled in this prospective study and implanted with Verisyse ICPIOLs (AMO). The
      anterior segment was evaluated by SP and UBM preoperatively and for at least 1
      month postoperatively. The statistical significance may be questionable due to
      the limited number (nine) of eyes. RESULTS: By SP and UBM, the distance between
      corneal endothelium and lens (anterior chamber depth) preoperatively was 3.10+/
      0.14 and 3.07+/-0.11 mm, respectively; between ICPIOL and corneal endothelium
      (pseudo-anterior chamber depth), 1.88+/-0.09 and 1.99+/-0.12 mm, respectively;
      between lens and posterior surface of ICPIOL (IL), 0.76+/-0.13 and 0.67+/-0.06
      mm, respectively; between superior optic edge and iris (SOEI), 0.23+/-0.23 and
      0.58+/-0.24 mm, respectively; between inferior optic edge and iris (IOEI), 0.07+/
      0.13 and 0.41+/-0.22 mm, respectively; between ICPIOL haptics and the angle of
      anterior chamber (HA), 0.90+/-0.17 and 1.45+/-0.13 mm, respectively. ACD was well
      correlated between the two methods, but PACD, IL, OEI, HA were not. The
      postoperative measures, except IL, were significantly different between the two
      methods. CONCLUSION: The differences between measurements by SP and UBM reveal
      the ICPIOL's position variations with change of body position. Nevertheless, it
      seems adequate that space is maintained between ICPIOL and corneal endothelium,
      angle, and crystalline lens. The ICPIOL implanted in phakic eyes seems a safe
      alternative for treatment of high myopia.

PMID- 17435686
TI  - The clinical utility of colour Doppler imaging.

PMID- 17435687
TI  - Eccentric macular hole formation associated with macular hole surgery.

PMID- 17435688
TI  - Transmuscular migration of solid silicone band.

PMID- 17435689
TI  - Optical coherence tomography in a patient with tobacco-alcohol amblyopia.
AB  - AIM: To report optical coherence tomography (OCT) finding in a patient with
      tobacco-alcohol amblyopia. METHODS: A 45-year-old man presented with a gradual
      decrease in vision over 4 years. He had smoked a half to one pack of cigarettes
      per day and had consumed 350 cc of gin per day for 30 years. A detailed
      ophthalmologic examination was performed. RESULTS: His corrected visual acuities
      were 20/800 OD and 20/200 OS. A Goldmann visual field examination showed ceco
      central scotomas in both eyes. OCT using a peripapillary Fast RNFL (retinal nerve
      fiber layer) programme showed a small decrease in the RNFL thickness of the
      superotemporal quadrant in the normative diagram of the right eye in spite of a
      markedly increased RNFL thickness in both eyes. CONCLUSION: During the phase of
      visual loss in a patient with tobacco-alcohol amblyopia, visual loss may precede
      optic disc changes as detected by OCT.

PMID- 17435690
TI  - Severe radiation retinopathy and optic neuropathy after brachytherapy for
      choroidal melanoma, treated by hyperbaric oxygen.

PMID- 17435691
TI  - Perceptions of patients to extending prescribing to nurses and pharmacists.

PMID- 17435692
TI  - Objective evaluation of cataract progression associated with a high dose
      intravitreal triamcinolone injection.
AB  - PURPOSE: To investigate the progression of cataract after a high dose (25 mg)
      intravitreal triamcinolone acetonide injection in patients with macular oedema
      secondary to diabetes and retinal vein occlusion. METHODS: This prospective
      interventional case series study included 38 patients (76 eyes) with diabetic
      retinopathy or retinal vein occlusion diagnosed with clinical examination and
      fluorescein angiography. The patients were treated with 25 mg IVTA in their one
      eye with macular oedema and the fellow eyes served as a control. Patients were
      asked to return the next day and weekly for 1 month and monthly thereafter by 6
      months post-operative. The progression of the cataract using photographic
      evaluation according to the Lens Opacities Classification System III was
      documented and statistical analysis was done using the Kaplan-Meier survival
      analysis and the log-rank test. RESULTS: Among the 38 treated eyes, there was an
      increase of cataract degree by 1 grade at the end of 6 months in 10 patients. The
      types of progressed cataract were PSC in seven patients, cortical in six
      patients, and nuclear sclerosis in one patient. Six months after the injections,
      there was a significantly higher rate of progression of PSC (P=0.023, log-rank
      test) and cortical opacities (P=0.011) in the treated group while the progression
      of nuclear cataract was not significantly different between the treated eye and
      the control eye. CONCLUSION: A high-dose (25 mg) intravitreal triamcinolone
      acetonide injection induces the progression of cortical and posterior subcapsular
      opacity in patients with diabetic macular oedema and retinal vein occlusion.

PMID- 17435693
TI  - Is the ISNT rule violated in early primary open-angle glaucoma--a scanning laser
      tomography study.
AB  - AIMS: To evaluate the relevance of the ISNT rule with reference to the optic
      nerve head, in differentiating normal and early glaucoma eyes and neuroretinal
      rim (NRR) area ratios as measures of glaucomatous optic neuropathy by confocal
      scanning laser ophthalmoscopy (Heidelberg retina tomography (HRT) II). METHODS:
      The study included 136 control eyes and 63 eyes of early primary open-angle
      glaucoma. Each patient underwent a complete ophthalmic examination, HRT II
      (software 2.01) and achromatic automated perimetry using the Humphrey field
      analyzer Full threshold program 30-2 or 24-2. Topographic HRT parameters (disc
      area and rim area) were compared between the groups. To assess the statistical
      significance of differences between the study groups, the Student's t-test was
      used. RESULTS: The ISNT rule was applicable in 71% of normal eyes and 68% of
      early glaucoma eyes. The superior to inferior area ratio was 0.96+/-0.01 in the
      normal group and 0.90+/-0.02 in the glaucoma group. There was a loss of
      approximately a quarter of the NRR in the inferotemporal and superotemporal
      quadrants. The inferonasal sector showed the least loss of NRR (4.34%).
      CONCLUSION: The inferior NRR is marginally wider than the superior NRR in about
      2/3 of normal eyes, but could not be clinically appreciated in many of these. The
      characteristic configuration of a normal optic disc with the rim width being
      greatest in the inferior disc region followed by the superior disc region was
      maintained even in most patients with early glaucoma.

PMID- 17435695
TI  - Consent to orthodontic treatment--is it working?
AB  - OBJECTIVE: To determine the level of patient and/or parent recall of previous
      consent to orthodontic treatment. DESIGN: Patients and/or parents of children who
      had been consented for orthodontic treatment were asked to complete a
      questionnaire on consent at least six months into their treatment. SETTING:
      Bristol Dental Hospital. SUBJECTS AND METHODS: Forty-one consecutive patients and
      eight of their parents, with a combined age range of 12-59 years, with 61% being
      female and 39% male. The patients, and where applicable their parents, were
      identified as having previously signed a consent form at least six months
      previously. Each was asked to complete a questionnaire on aspects of the consent
      process. RESULTS: Patients and parents demonstrated a high level of recall for
      the consent process concerning appliance type (89.8%), the reasons for treatment
      (96%), risks (75.5%), length of treatment (83.3%), the opportunity to ask
      questions (96%), and whether other information was provided (94%). However,
      further questioning on risks demonstrated poor recall for important factors such
      as decay (36.8%), root resorption (less than 21%), retention (56.3%) and length
      of retention (35%). CONCLUSIONS: Overall the consent process works well but
      specific areas of concern centre around the risks of orthodontic treatment.

PMID- 17435696
TI  - Knowledge of dental trauma first aid (DTFA): the example of avulsed incisors in
      casualty departments and schools in London.
AB  - OBJECTIVE: To investigate awareness and practices of dental trauma first aid
      (DTFA) in hospital emergency settings and in primary and secondary schools in
      London. DESIGN: A cross-sectional study using self-administered questionnaires
      and semi-structured interviews. SETTING: Primary and secondary schools and
      casualty/emergency and walk-in casualty centres in London in 2005. SUBJECTS AND
      METHODS: A randomly selected sample of 125 schools and a total of 31 walk-in
      casualty centres, providing services for five randomly selected London boroughs.
      A person responsible for emergency care of children represented each of these
      study sites. RESULTS: Response rates of 81.6% and 87% were achieved for schools
      and casualty/emergency centres respectively. The school respondents who had
      previously received advice on DTFA were three times more likely to be willing to
      replant an avulsed tooth compared to those who had not. A third of casualty
      personnel showed gaps in knowledge in DTFA. Results from schools showed an
      unwillingness to start emergency action mainly due to perceived inadequacy in
      knowledge/skills and also for legal reasons. CONCLUSION: There is the need for
      further studies focused on the barriers resulting in unwillingness to provide
      DTFA among school personnel and clarification regarding issues of responsibility
      and acceptable levels of competence of professionals other than dentists.

PMID- 17435697
TI  - A profession to the core.

PMID- 17435698
TI  - Conflict resolution.

PMID- 17435699
TI  - Public identities.

PMID- 17435700
TI  - Unacknowledged.

PMID- 17435701
TI  - Close partnerships.

PMID- 17435702
TI  - No passage to Indians.

PMID- 17435703
TI  - Compromised insertion.

PMID- 17435704
TI  - UDA calculations.

PMID- 17435705
TI  - Eyeball teeth.

PMID- 17435719
TI  - Surgical laser use in implantology and endodontics.
AB  - The use of surgical lasers has been advocated to aid in the placement and second
      stage recovery of dental implants, together with soft tissue contouring. In
      addition, laser use has been suggested as an aid in decontamination of the
      implant surface in cases of peri-implantitis. In endodontics, the association of
      laser energy with dentine hypersensitivity, bacteriocidal action and pulp
      capping, has led to a growing number of reports as to its beneficial use,
      together with claims of morphological changes in the canal wall, to enhance
      endodontic treatment success.

PMID- 17435706
TI  - Mealy-mouthed rhetoric.

PMID- 17435720
TI  - Introduction to email.
AB  - Email is a computer based method of sending messages from one computer to
      another. From its humble beginnings 40 years, it has matured to become a crucial
      tool in utilising the power of the Internet. More people have access to email
      than to any other Internet application, and despite the problems with spam email
      and viruses, email remains popular because of its low cost, universality and ease
      of use. This section looks at the advantages of email over other methods of
      communication, how email works and other ways of communicating using the
      Internet.

PMID- 17435721
TI  - Needle breakage following inferior alveolar nerve block: implications and
      management.
AB  - Needle breakage following inferior alveolar nerve block is a rare complication in
      current dental practice. We report a case of delayed retrieval of a broken needle
      with the use of modern imaging modalities. In addition, possible causes of needle
      breakage and preventative measures, indications and timing of removal,
      localisation techniques and surgical approaches are discussed.

PMID- 17435722
TI  - Bullets in the mandible over 12 years: a case report.
AB  - Foreign bodies that enter a patient as a result of trauma are contaminated and
      produce a range of symptoms. We report a case in which radiographic evidence of
      foreign bodies in the mandible exposed a history involving a gunshot injury to
      the chin. The patient did not have any major complaints relating to the bullets
      lodged in his mandible or any symptoms of lead poisoning. These foreign bodies
      have remained clinically silent for more than 12 years.

PMID- 17435729
TI  - Portable digital assistants (PDAs) in dentistry: part I.
AB  - AIM: To provide a basic understanding of the features of a portable digital
      assistant (PDA) and how it may be useful for the general dental practitioner.
      OBJECTIVES: To outline the various types, functions and applications of a PDA and
      suggest its use for the dental professional now and in the future. To enable
      appreciation of the technology and educational evaluation carried out in the
      pilot study reported in Part II. DESIGN: Part I is a descriptive account of the
      use and function of the PDA in dentistry and its potential for the future.
      METHOD: A review of the literature was carried out drawing on evidence from
      general healthcare and assessments of portable computing aids evaluated in a
      dentally related setting. RESULTS Choosing a PDA for use in dental practice is
      complex but should be based on the user's needs mapped to key features, size and
      cost of the device. CONCLUSION: No ideal customisable mobile digital solution
      currently exists but evidence from general healthcare use suggests that there are
      valuable features that can aid the general dental practitioners such as personal
      management and point of source assistance.

PMID- 17435740
TI  - Protecting children.
AB  - Safeguarding children from maltreatment and neglect is part of the responsibility
      of all health professionals, and dental practitioners may be in a unique position
      to recognise and respond to concerns of this kind. This article outlines some of
      the ways that abuse can present to the dental team and describes the action that
      should be taken if abuse is suspected in a young patient.

PMID- 17435746
TI  - Chloroplastic photorespiratory bypass increases photosynthesis and biomass
      production in Arabidopsis thaliana.
AB  - We introduced the Escherichia coli glycolate catabolic pathway into Arabidopsis
      thaliana chloroplasts to reduce the loss of fixed carbon and nitrogen that occurs
      in C(3) plants when phosphoglycolate, an inevitable by-product of photosynthesis,
      is recycled by photorespiration. Using step-wise nuclear transformation with five
      chloroplast-targeted bacterial genes encoding glycolate dehydrogenase, glyoxylate
      carboligase and tartronic semialdehyde reductase, we generated plants in which
      chloroplastic glycolate is converted directly to glycerate. This reduces, but
      does not eliminate, flux of photorespiratory metabolites through peroxisomes and
      mitochondria. Transgenic plants grew faster, produced more shoot and root
      biomass, and contained more soluble sugars, reflecting reduced photorespiration
      and enhanced photosynthesis that correlated with an increased chloroplastic CO(2)
      concentration in the vicinity of ribulose-1,5-bisphosphate carboxylase/oxygenase.
      These effects are evident after overexpression of the three subunits of glycolate
      dehydrogenase, but enhanced by introducing the complete bacterial glycolate
      catabolic pathway. Diverting chloroplastic glycolate from photorespiration may
      improve the productivity of crops with C(3) photosynthesis.

PMID- 17435747
TI  - Isolation of engineered, full-length antibodies from libraries expressed in
      Escherichia coli.
AB  - We describe facile isolation of full-length IgG antibodies from combinatorial
      libraries expressed in E. coli. Full-length heavy and light chains are secreted
      into the periplasm, where they assemble into aglycosylated IgGs that are captured
      by an Fc-binding protein that is tethered to the inner membrane. After
      permeabilizing the outer membrane, spheroplast clones expressing so-called E
      clonal antibodies, which specifically recognize fluorescently labeled antigen,
      are selected using flow cytometry. Screening of a library constructed from an
      immunized animal yielded several antibodies with nanomolar affinities toward the
      protective antigen of Bacillus anthracis.

PMID- 17435748
TI  - DEAD-box RNA helicase subunits of the Drosha complex are required for processing
      of rRNA and a subset of microRNAs.
AB  - MicroRNAs (miRNAs) control cell proliferation, differentiation and fate through
      modulation of gene expression by partially base-pairing with target mRNA
      sequences. Drosha is an RNase III enzyme that is the catalytic subunit of a large
      complex that cleaves pri-miRNAs with distinct structures into pre-miRNAs. Here,
      we show that both the p68 and p72 DEAD-box RNA helicase subunits in the mouse
      Drosha complex are indispensable for survival in mice, and both are required for
      primary miRNA and rRNA processing. Gene disruption of either p68 or p72 in mice
      resulted in early lethality, and in both p68(-/-) and p72(-/-) embryos,
      expression levels of a set of, but not all, miRNAs and 5.8S rRNA were
      significantly lowered. In p72(-/-) MEF cells, expression of p72, but not a mutant
      lacking ATPase activity, restored the impaired expression of miRNAs and 5.8S
      rRNA. Furthermore, we purified the large complex of mouse Drosha and showed it
      could generate pre-miRNA and 5.8S rRNA in vitro. Thus, we suggest that DEAD-box
      RNA helicase subunits are required for recognition of a subset of primary miRNAs
      in mDrosha-mediated processing.

PMID- 17435749
TI  - The outer plate in vertebrate kinetochores is a flexible network with multiple
      microtubule interactions.
AB  - Intricate interactions between kinetochores and microtubules are essential for
      the proper distribution of chromosomes during mitosis. A crucial long-standing
      question is how vertebrate kinetochores generate chromosome motion while
      maintaining attachments to the dynamic plus ends of the multiple kinetochore MTs
      (kMTs) in a kinetochore fibre. Here, we demonstrate that individual kMTs in
      PtK(1) cells are attached to the kinetochore outer plate by several fibres that
      either embed the microtubule plus-end tips in a radial mesh, or extend out from
      the outer plate to bind microtubule walls. The extended fibres also interact with
      the walls of nearby microtubules that are not part of the kinetochore fibre.
      These structural data, in combination with other recent reports, support a
      network model of kMT attachment wherein the fibrous network in the unbound outer
      plate, including the Hec1-Ndc80 complex, dissociates and rearranges to form kMT
      attachments.

PMID- 17435750
TI  - The neural progenitor-specifying activity of FoxG1 is antagonistically regulated
      by CKI and FGF.
AB  - FoxG1 is an evolutionarily conserved, winged-helix transcriptional repressor that
      maintains progenitor cells in the vertebrate forebrain. How the activity of FoxG1
      is regulated is not known. Here, we report that in the developing Xenopus and
      mouse forebrain, FoxG1 is nuclear in progenitor cells but cytoplasmic in
      differentiating cells. The subcellular localisation of FoxG1 is regulated at the
      post-translational level by casein kinase I (CKI) and fibroblast growth factor
      (FGF) signalling. CKI phosphorylation of Ser 19 of FoxG1 promotes nuclear import,
      whereas FGF-induced phosphorylation of Thr 226 promotes nuclear export.
      Interestingly, FGF-induced phosphorylation of FoxG1 is mediated Akt kinase (also
      known as protein B kinase, PKB) kinase, rather than the MAPK pathway.
      Phosphorylation of endogenous FoxG1 is blocked by CKI and Akt inhibitors. In the
      mouse olfactory placode cell line OP27, and in cortical progenitors, increased
      FGF signalling causes FoxG1 to exit the nucleus and promotes neuronal
      differentiation, whereas FGF and Akt inhibitors block this effect. Thus, CKI and
      FGF signalling converge on an antagonistic regulation of FoxG1, which in turn
      controls neurogenesis in the forebrain.

PMID- 17435752
TI  - Channelrhodopsin-2-assisted circuit mapping of long-range callosal projections.
AB  - The functions of cortical areas depend on their inputs and outputs, but the
      detailed circuits made by long-range projections are unknown. We show that the
      light-gated channel channelrhodopsin-2 (ChR2) is delivered to axons in pyramidal
      neurons in vivo. In brain slices from ChR2-expressing mice, photostimulation of
      ChR2-positive axons can be transduced reliably into single action potentials.
      Combining photostimulation with whole-cell recordings of synaptic currents makes
      it possible to map circuits between presynaptic neurons, defined by ChR2
      expression, and postsynaptic neurons, defined by targeted patching. We applied
      this technique, ChR2-assisted circuit mapping (CRACM), to map long-range callosal
      projections from layer (L) 2/3 of the somatosensory cortex. L2/3 axons connect
      with neurons in L5, L2/3 and L6, but not L4, in both ipsilateral and
      contralateral cortex. In both hemispheres the L2/3-to-L5 projection is stronger
      than the L2/3-to-L2/3 projection. Our results suggest that laminar specificity
      may be identical for local and long-range cortical projections.

PMID- 17435751
TI  - N-terminal alpha-methylation of RCC1 is necessary for stable chromatin
      association and normal mitosis.
AB  - Regulator of chromatin condensation 1 (RCC1) is the only known guanine nucleotide
      exchange factor for the Ran GTPase and has pivotal roles in nucleo-cytoplasmic
      transport, mitosis, and nuclear-envelope assembly. RCC1 associates dynamically
      with chromatin through binding to histones H2A and/or H2B in a Ran-regulated
      manner. Here, we report that, unexpectedly, the amino-terminal serine or proline
      residue of RCC1 is uniquely methylated on its alpha-amino group. Methylation
      requires removal of the initiating methionine, and the presence of proline and
      lysine at positions 3 and 4, respectively. Methylation-defective mutants of RCC1
      bind less effectively than wild-type protein to chromatin during mitosis, which
      causes spindle-pole defects. We propose a bimodal attachment mechanism for RCC1
      in which the tail promotes stable RCC1 association with chromatin through DNA
      binding in an alpha-N-methylation-dependent manner. These data provide the first
      known function for N-terminal protein methylation.

PMID- 17435753
TI  - Double dissociation between long-term depression and dendritic spine morphology
      in cerebellar Purkinje cells.
AB  - Experiments in hippocampal area CA1 suggest that long-term potentiation could be
      associated with spine addition and enlargement, and long-term depression (LTD)
      with spine shrinkage and loss. Is this a general principle of synaptic
      plasticity? We used two-photon microscopy to measure dendritic spines in rat
      cerebellar Purkinje cells. Neither local synaptic induction of LTD nor global
      chemical induction of LTD changed spine number or size. Conversely, a
      manipulation that evoked persistent dendritic spine retraction did not alter
      parallel fiber-evoked excitatory postsynaptic currents.

PMID- 17435754
TI  - Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell
      based ALS model.
AB  - Here we report an in vitro model system for studying the molecular and cellular
      mechanisms that underlie the neurodegenerative disease amyotrophic lateral
      sclerosis (ALS). Embryonic stem cells (ESCs) derived from mice carrying normal or
      mutant transgenic alleles of the human SOD1 gene were used to generate motor
      neurons by in vitro differentiation. These motor neurons could be maintained in
      long-term coculture either with additional cells that arose during
      differentiation or with primary glial cells. Motor neurons carrying either the
      nonpathological human SOD1 transgene or the mutant SOD1(G93A) allele showed
      neurodegenerative properties when cocultured with SOD1(G93A) glial cells. Thus,
      our studies demonstrate that glial cells carrying a human SOD1(G93A) mutation
      have a direct, non-cell autonomous effect on motor neuron survival. More
      generally, our results show that ESC-based models of disease provide a powerful
      tool for studying the mechanisms of neural degeneration. These phenotypes
      displayed in culture could provide cell-based assays for the identification of
      new ALS drugs.

PMID- 17435755
TI  - Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic
      to motor neurons.
AB  - Mutations in superoxide dismutase-1 (SOD1) cause a form of the fatal paralytic
      disorder amyotrophic lateral sclerosis (ALS), presumably by a combination of cell
      autonomous and non-cell-autonomous processes. Here, we show that expression of
      mutated human SOD1 in primary mouse spinal motor neurons does not provoke motor
      neuron degeneration. Conversely, rodent astrocytes expressing mutated SOD1 kill
      spinal primary and embryonic mouse stem cell-derived motor neurons. This is
      triggered by soluble toxic factor(s) through a Bax-dependent mechanism. However,
      mutant astrocytes do not cause the death of spinal GABAergic or dorsal root
      ganglion neurons or of embryonic stem cell-derived interneurons. In contrast to
      astrocytes, fibroblasts, microglia, cortical neurons and myocytes expressing
      mutated SOD1 do not cause overt neurotoxicity. These findings indicate that
      astrocytes may play a role in the specific degeneration of spinal motor neurons
      in ALS. Identification of the astrocyte-derived soluble factor(s) may have far
      reaching implications for ALS from both a pathogenic and therapeutic standpoint.

PMID- 17435757
TI  - Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes
      male infertility.
AB  - The World Health Organization conservatively estimates that 80 million people
      suffer from infertility worldwide. Male factors are believed to be responsible
      for 20-50% of all infertility cases, but microdeletions of the Y chromosome are
      the only genetic defects altering human spermatogenesis that have been reported
      repeatedly. We focused our work on infertile men with a normal somatic karyotype
      but typical spermatozoa mainly characterized by large heads, a variable number of
      tails and an increased chromosomal content (OMIM 243060). We performed a genome
      wide microsatellite scan on ten infertile men presenting this characteristic
      phenotype. In all of these men, we identified a common region of homozygosity
      harboring the aurora kinase C gene (AURKC) with a single nucleotide deletion in
      the AURKC coding sequence. In addition, we show that this founder mutation
      results in premature termination of translation, yielding a truncated protein
      that lacks the kinase domain. We conclude that the absence of AURKC causes male
      infertility owing to the production of large-headed multiflagellar polyploid
      spermatozoa.

PMID- 17435756
TI  - Genome-wide association study identifies new susceptibility loci for Crohn
      disease and implicates autophagy in disease pathogenesis.
AB  - We present a genome-wide association study of ileal Crohn disease and two
      independent replication studies that identify several new regions of association
      to Crohn disease. Specifically, in addition to the previously established CARD15
      and IL23R associations, we identified strong and significantly replicated
      associations (combined P < 10(-10)) with an intergenic region on 10q21.1 and a
      coding variant in ATG16L1, the latter of which was also recently reported by
      another group. We also report strong associations with independent replication to
      variation in the genomic regions encoding PHOX2B, NCF4 and a predicted gene on
      16q24.1 (FAM92B). Finally, we demonstrate that ATG16L1 is expressed in intestinal
      epithelial cell lines and that functional knockdown of this gene abrogates
      autophagy of Salmonella typhimurium. Together, these findings suggest that
      autophagy and host cell responses to intracellular microbes are involved in the
      pathogenesis of Crohn disease.

PMID- 17435758
TI  - Direct quantitative trait locus mapping of mammalian metabolic phenotypes in
      diabetic and normoglycemic rat models.
AB  - Characterizing the relationships between genomic and phenotypic variation is
      essential to understanding disease etiology. Information-dense data sets derived
      from pathophysiological, proteomic and transcriptomic profiling have been applied
      to map quantitative trait loci (QTLs). Metabolic traits, already used in QTL
      studies in plants, are essential phenotypes in mammalian genetics to define
      disease biomarkers. Using a complex mammalian system, here we show chromosomal
      mapping of untargeted plasma metabolic fingerprints derived from NMR
      spectroscopic analysis in a cross between diabetic and control rats. We propose
      candidate metabolites for the most significant QTLs. Metabolite profiling in
      congenic strains provided evidence of QTL replication. Linkage to a gut microbial
      metabolite (benzoate) can be explained by deletion of a uridine diphosphate
      glucuronosyltransferase. Mapping metabotypic QTLs provides a practical approach
      to understanding genome-phenotype relationships in mammals and may uncover deeper
      biological complexity, as extended genome (microbiome) perturbations that affect
      disease processes through transgenomic effects may influence QTL detection.

PMID- 17435759
TI  - Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia.
AB  - We identified a duplication of the MYB oncogene in 8.4% of individuals with T
      cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The
      duplication is associated with a threefold increase in MYB expression, and
      knockdown of MYB expression initiates T cell differentiation. Our results
      identify duplication of MYB as an oncogenic event and suggest that MYB could be a
      therapeutic target in human T-ALL.

PMID- 17435760
TI  - A crucial function of SGT1 and HSP90 in inflammasome activity links mammalian and
      plant innate immune responses.
AB  - The family of mammalian Nod-like receptors (NLRs) consists of critical
      intracellular immune proteins structurally related to plant resistance proteins.
      The NLRs NALP3 and IPAF, for example, can each form a multiprotein
      proinflammatory complex called the 'inflammasome', and mutations in the gene
      encoding Nod2, another NLR, are positively associated with Crohn disease. Here we
      show that many NLRs interacted with the ubiquitin ligase-associated protein SGT1
      and heat-shock protein 90 (HSP90), both of which have plant orthologs essential
      for R-protein responses. 'Knockdown' of SGT1 by small interfering RNA or chemical
      inhibition of HSP90 abrogated inflammasome activity, and inhibition of HSP90
      blocked Nod2-mediated activation of the transcription factor NF-kappaB and
      reduced NALP3-mediated gout-like inflammation in mice. Our data demonstrate a
      similarity in one type of innate immunity in plants and mammals that is
      consistent with convergent evolution of a shared mechanism.

PMID- 17435761
TI  - Dispensing and surface-induced crystallization of zeptolitre liquid metal-alloy
      drops.
AB  - The controlled delivery of fluids is a key process in nature and in many areas of
      science and technology, where pipettes or related devices are used for dispensing
      well-defined fluid volumes. Existing pipettes are capable of delivering fluids
      with attolitre (10-18 l) accuracy at best. Studies on phase transformations of
      nanoscale objects would benefit from the controlled dispensing and manipulation
      of much smaller droplets. In contrast to nanoparticle melting whose fundamental
      pathway was studied extensively, experiments on crystallization, testing
      classical nucleation theory, are hindered by the influence of support interfaces.
      Experiments on free-standing fluid drops are extremely challenging. Here, we
      demonstrate the operation of a pipette, which, observed by transmission electron
      microscopy, delivers a metal-alloy melt with zeptolitre (10-21 l) resolution. We
      use this exquisite control to produce nearly free-standing Au72Ge28 drops
      suspended by an atomic-scale meniscus at the pipette tip, and to image their
      phase transformations with near-atomic resolution. Our observations of the liquid
      solid transition challenge classical nucleation theory by providing experimental
      evidence for an intrinsic crystallization pathway of nanometre-sized fluid drops
      that avoids nucleation in the interior, but instead proceeds via liquid-state
      surface faceting as a precursor to surface-induced crystallization.

PMID- 17435762
TI  - Multifunctional chondroitin sulphate for cartilage tissue-biomaterial
      integration.
AB  - A biologically active, high-strength tissue adhesive is needed for numerous
      medical applications in tissue engineering and regenerative medicine. Integration
      of biomaterials or implants with surrounding native tissue is crucial for both
      immediate functionality and long-term performance of the tissue. Here, we use the
      biopolymer chondroitin sulphate (CS), one of the major components of cartilage
      extracellular matrix, to develop a novel bioadhesive that is readily applied and
      acts quickly. CS was chemically functionalized with methacrylate and aldehyde
      groups on the polysaccharide backbone to chemically bridge biomaterials and
      tissue proteins via a twofold covalent link. Three-dimensional hydrogels (with
      and without cells) bonded to articular cartilage defects. In in vitro and in vivo
      functional studies this approach led to mechanical stability of the hydrogel and
      tissue repair in cartilage defects.

PMID- 17435763
TI  - Multiplexed single-molecule assay for enzymatic activity on flow-stretched DNA.
AB  - We report a single-molecule assay for nucleic-acid enzymes on flow-stretched DNA
      templates. To facilitate the detection of slow or intermittent enzymatic
      activities, we developed the assay with 15-nm spatial resolution at a frame rate
      of 1 Hz and approximately 10 nm mechanical stability over the timescale of hours.
      With multiplexed data collection, we applied the assay to phi29 DNA polymerase,
      HIV-1 reverse transcriptase, lambda exonuclease and Escherichia coli RNA
      polymerase.

PMID- 17435764
TI  - A model system for analyzing somatic mutations in Drosophila melanogaster.
AB  - Presently there are no good assays for comparing somatic mutation frequencies and
      spectra between different vertebrate and invertebrate organisms. Here we describe
      a new lacZ mutation reporter system in D. melanogaster, which complements
      existing systems in the mouse. The results obtained with the new model indicate
      two-to threefold higher frequencies of spontaneous mutations than in the mouse,
      with most of the mutations characterized as large genome rearrangements.

PMID- 17435765
TI  - Structural and biophysical studies of PCSK9 and its mutants linked to familial
      hypercholesterolemia.
AB  - Proprotein convertase subtilisin kexin type 9 (PCSK9) lowers the abundance of
      surface low-density lipoprotein (LDL) receptor through an undefined mechanism.
      The structure of human PCSK9 shows the subtilisin-like catalytic site blocked by
      the prodomain in a noncovalent complex and inaccessible to exogenous ligands, and
      that the C-terminal domain has a novel fold. Biosensor studies show that PCSK9
      binds the extracellular domain of LDL receptor with K(d) = 170 nM at the neutral
      pH of plasma, but with a K(d) as low as 1 nM at the acidic pH of endosomes. The
      D374Y gain-of-function mutant, associated with hypercholesterolemia and early
      onset cardiovascular disease, binds the receptor 25 times more tightly than wild
      type PCSK9 at neutral pH and remains exclusively in a high-affinity complex at
      the acidic pH. PCSK9 may diminish LDL receptors by a mechanism that requires
      direct binding but not necessarily receptor proteolysis.

PMID- 17435766
TI  - H-NS cooperative binding to high-affinity sites in a regulatory element results
      in transcriptional silencing.
AB  - H-NS is a protein of the bacterial nucleoid involved in DNA compaction and
      transcription regulation. In vivo, H-NS selectively silences specific genes of
      the bacterial chromosome. However, many studies have concluded that H-NS binds
      sequence-independently to DNA, leaving the molecular basis for its selectivity
      unexplained. We show that the negative regulatory element (NRE) of the
      supercoiling-sensitive Escherichia coliproU gene contains two identical high
      affinity binding sites for H-NS. Cooperative binding of H-NS is abrogated by
      changes in DNA superhelical density and temperature. We further demonstrate that
      the high-affinity sites nucleate cooperative binding and establish a
      nucleoprotein structure required for silencing. Mutations in these sites result
      in loss of repression by H-NS. In this model, silencing at proU, and by inference
      at other genes directly regulated by H-NS, is tightly controlled by the
      cooperativity between bound H-NS molecules.

PMID- 17435767
TI  - The uncoupled chloride conductance of a bacterial glutamate transporter homolog.
AB  - Glutamate transporters (EAATs) are pivotal in mammalian synaptic transmission,
      tightly regulating synaptic levels of this excitatory neurotransmitter. In
      addition to coupled glutamate transport, the EAATs also show an uncoupled Cl(-)
      conductance, whose physiological importance has recently been demonstrated.
      Little is yet known about the molecular mechanism of chloride permeation. Here we
      show that Glt(Ph), a bacterial EAAT homolog whose structure has been determined,
      displays an uncoupled Cl(-) conductance that can determine the rate of substrate
      uptake. A mutation analogous to one known to specifically affect Cl(-) movement
      in EAAT1 has similar effects on Glt(Ph), suggesting that this protein is an
      excellent structural model for understanding Cl(-) permeation through the EAATs.
      We also observed an uncoupled Cl(-) conductance in another bacterial EAAT homolog
      but not in a homolog of the Na(+)/Cl(-)-coupled neurotransmitter transporters.

PMID- 17435768
TI  - Structure-based design of a pathway-specific nuclear import inhibitor.
AB  - Kapbeta2 (also called transportin) recognizes PY nuclear localization signal
      (NLS), a new class of NLS with a R/H/Kx((2-5))PY motif. Here we show that
      Kapbeta2 complexes containing hydrophobic and basic PY-NLSs, as classified by the
      composition of an additional N-terminal motif, converge in structure only at
      consensus motifs, which explains ligand diversity. On the basis of these data and
      complementary biochemical analyses, we designed a Kapbeta2-specific nuclear
      import inhibitor, M9M.

PMID- 17435769
TI  - Zinc pyrithione-mediated activation of voltage-gated KCNQ potassium channels
      rescues epileptogenic mutants.
AB  - KCNQ potassium channels are activated by changes in transmembrane voltage and
      play an important role in controlling electrical excitability. Human mutations of
      KCNQ2 and KCNQ3 potassium channel genes result in reduction or loss of channel
      activity and cause benign familial neonatal convulsions (BFNCs). Thus, small
      molecules capable of augmenting KCNQ currents are essential both for
      understanding the mechanism of channel activity and for developing therapeutics.
      We performed a high-throughput screen in search for agonistic compounds
      potentiating KCNQ potassium channels. Here we report identification of a new
      opener, zinc pyrithione (1), which activates both recombinant and native KCNQ M
      currents. Interactions with the channel protein cause an increase of single
      channel open probability that could fully account for the overall conductance
      increase. Separate point mutations have been identified that either shift the
      concentration dependence or affect potentiation efficacy, thereby providing
      evidence for residues influencing ligand binding and downstream events.
      Furthermore, zinc pyrithione is capable of rescuing the mutant channels causal to
      BFNCs.

PMID- 17435770
TI  - Osteopontin has a crucial role in allergic airway disease through regulation of
      dendritic cell subsets.
AB  - Osteopontin (Opn) is important for T helper type 1 (T(H)1) immunity and
      autoimmunity. However, the role of this cytokine in T(H)2-mediated allergic
      disease as well as its effects on primary versus secondary antigenic encounters
      remain unclear. Here we demonstrate that OPN is expressed in the lungs of
      asthmatic individuals and that Opn-s, the secreted form of Opn, exerts opposing
      effects on mouse T(H)2 effector responses and subsequent allergic airway disease:
      pro-inflammatory at primary systemic sensitization, and anti-inflammatory during
      secondary pulmonary antigenic challenge. These effects of Opn-s are mainly
      mediated by the regulation of T(H)2-suppressing plasmacytoid dendritic cells
      (DCs) during primary sensitization and T(H)2-promoting conventional DCs during
      secondary antigenic challenge. Therapeutic administration of recombinant Opn
      during pulmonary secondary antigenic challenge decreased established T(H)2
      responses and protected mice from allergic disease. These effects on T(H)2
      allergic responses suggest that Opn-s is an important therapeutic target and
      provide new insight into its role in immunity.

PMID- 17435771
TI  - MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and
      atherogenic cell recruitment.
AB  - The cytokine macrophage migration inhibitory factor (MIF) plays a critical role
      in inflammatory diseases and atherogenesis. We identify the chemokine receptors
      CXCR2 and CXCR4 as functional receptors for MIF. MIF triggered G(alphai)- and
      integrin-dependent arrest and chemotaxis of monocytes and T cells, rapid integrin
      activation and calcium influx through CXCR2 or CXCR4. MIF competed with cognate
      ligands for CXCR4 and CXCR2 binding, and directly bound to CXCR2. CXCR2 and CD74
      formed a receptor complex, and monocyte arrest elicited by MIF in inflamed or
      atherosclerotic arteries involved both CXCR2 and CD74. In vivo, Mif deficiency
      impaired monocyte adhesion to the arterial wall in atherosclerosis-prone mice,
      and MIF-induced leukocyte recruitment required Il8rb (which encodes Cxcr2).
      Blockade of Mif but not of canonical ligands of Cxcr2 or Cxcr4 in mice with
      advanced atherosclerosis led to plaque regression and reduced monocyte and T-cell
      content in plaques. By activating both CXCR2 and CXCR4, MIF displays chemokine
      like functions and acts as a major regulator of inflammatory cell recruitment and
      atherogenesis. Targeting MIF in individuals with manifest atherosclerosis can
      potentially be used to treat this condition.

PMID- 17435773
TI  - Cancer research in China: a special focus by cell research.

PMID- 17435772
TI  - Rhesus monkey TRIM5alpha restricts HIV-1 production through rapid degradation of
      viral Gag polyproteins.
AB  - Mammalian cells have developed diverse strategies to restrict retroviral
      infection. Retroviruses have therefore evolved to counteract such restriction
      factors, in order to colonize their hosts. Tripartite motif-containing 5 isoform
      alpha (TRIM5alpha) protein from rhesus monkey (TRIM5alpharh) restricts human
      immunodeficiency virus type 1 (HIV-1) infection at a postentry, preintegration
      stage in the viral life cycle, by recognizing the incoming capsid and promoting
      its premature disassembly. TRIM5alpha comprises an RBCC (RING, B-box 2 and coiled
      coil motifs) domain and a B30.2(SPRY) domain. Sequences in the B30.2(SPRY) domain
      dictate the potency and specificity of the restriction. As TRIM5alpharh targets
      incoming mature HIV-1 capsid, but not precursor Gag, it was assumed that
      TRIM5alpharh did not affect HIV-1 production. Here we provide evidence that
      TRIM5alpharh, but not its human ortholog (TRIM5alphahu), blocks HIV-1 production
      through rapid degradation of HIV-1 Gag polyproteins. The specificity for this
      restriction is determined by sequences in the RBCC domain. Our observations
      suggest that TRIM5alpharh interacts with HIV-1 Gag during or before Gag assembly
      through a mechanism distinct from the well-characterized postentry restriction.
      This finding demonstrates a cellular factor blocking HIV-1 production by actively
      degrading a viral protein. Further understanding of this previously unknown
      restriction mechanism may reveal new targets for future anti-HIV-1 therapy.

PMID- 17435774
TI  - Xom as a novel partner of Lef/Tcfs during dorsal-ventral patterning of the
      Xenopus embryo.

PMID- 17435775
TI  - Side effects of Tamiflu: clues from an Asian single nucleotide polymorphism.

PMID- 17435780
TI  - Signaling to structures: skin appendages, development and diseases--meeting
      report of the 55th annual Montagna Symposium on the Biology of Skin.

PMID- 17435781
TI  - CaR talk: the calcium receptor finds new places to park.
AB  - The study by Tu et al. in this issue details the surprising finding that not only
      is the CaR active intracellularly but also its intracellular localization
      includes both the ER, traditionally thought of as the main intracellular Ca2+
      signaling store, and the Golgi, more recently shown to be important in
      keratinocyte signaling.

PMID- 17435782
TI  - Fishing for allergens hiding as prohaptens.
AB  - Enzymes of the cytochrome P450 (CYP) superfamily are the most versatile and
      important class of drug-metabolizing enzymes, involved in the metabolism of
      xenobiotics to which human skin is exposed. Bergstrom et al. used a recombinant
      human CYP cocktail in ratios that simulate those found in human skin for the
      purpose of identifying prohapten metabolites of otherwise inert molecules.

PMID- 17435783
TI  - Patterning skin pigmentation via dickkopf.
AB  - One of the striking regional variations in skin is its pigmentation. Yamaguchi et
      al. further dissect the mechanism of regional pigmentation by assessing the
      effects of dickkopf 1 (DKK1), an antagonist of the Wnt pathway produced in
      lightly pigmented skin, on melanocyte gene expression. The results provide a
      plethora of candidate genes that may mediate DKK1's inhibitory effects on
      melanocyte function.

PMID- 17435784
TI  - The dumb ErbB receptor helps healing.
AB  - ErbB3 receptor is a member of the epidermal growth factor (EGF) receptor (ErbB1)
      family. Okwueze et al. have transfected this receptor in a pig model of wounds
      and demonstrate that it accelerates the resurfacing of the wounds when combined
      with epiregulin or heparin-binding EGF. Currently, only hypotheses can be
      proposed to explain the observations.

PMID- 17435785
TI  - Keratinocyte-fibroblast interactions in wound healing.
AB  - Cutaneous tissue repair aims at restoring the barrier function of the skin. To
      achieve this, defects need to be replaced by granulation tissue to form new
      connective tissue, and epithelial wound closure is required to restore the
      physical barrier. Different wound-healing phases are recognized, starting with an
      inflammation-dominated early phase giving way to granulation tissue build-up and
      scar remodeling after epithelial wound closure has been achieved. In the
      granulation tissue, mesenchymal cells are maximally activated, cells proliferate,
      and synthesize huge amounts of extracellular matrix. Epithelial cells also
      proliferate and migrate over the provisional matrix of the underlying granulation
      tissue, eventually closing the defect. This review focuses on the role of
      keratinocyte-fibroblast interactions in the wound-healing process. There is ample
      evidence that keratinocytes stimulate fibroblasts to synthesize growth factors,
      which in turn will stimulate keratinocyte proliferation in a double paracrine
      manner. Moreover, fibroblasts can acquire a myofibroblast phenotype under the
      control of keratinocytes. This depends on a finely tuned balance between a
      proinflammatory or a transforming growth factor (TGF)-beta-dominated environment.
      As the phenotype of fibroblasts from different tissues or body sites becomes
      better defined, we may understand their individual contribution in wound healing
      in more detail and possibly explain different clinical outcomes.

PMID- 17435786
TI  - The inflammation-fibrosis link? A Jekyll and Hyde role for blood cells during
      wound repair.
AB  - The healing of a skin wound is a complex process involving many cell lineages. In
      adult tissues, repair is always accompanied by a robust inflammatory response,
      which is necessary to counter the potential for infection at any site where the
      skin barrier is breached. Unlike embryonic tissues that can repair perfectly
      without a remnant scar at the wound site, adult tissue repair always leads to
      formation of a fibrotic scar where the wound has healed. In recent years, it has
      become clear that the wound inflammatory response may be, at least in part,
      responsible for fibrosis at sites of tissue repair. In this review, we consider
      the beneficial vs the detrimental functions of inflammatory cells during the
      repair response and compare data from other tissues, the lung, and liver, where
      fibrosis and its resolution may be related to a damage-triggered inflammatory
      response. We also consider how it may be possible to molecularly disentangle the
      potentially good from the bad influences of inflammatory cells during tissue
      repair and how fundamental studies in inflammatory cell biology may prove the way
      forward for development of drug targets in this respect.

PMID- 17435787
TI  - Tissue engineering for cutaneous wounds.
AB  - Skin, the largest organ in the body, protects against toxins and microorganisms
      in the environment and serves to prevent dehydration of all non-aquatic animals.
      Immune surveillance, sensory detection, and self-healing are other critical
      functions of the skin. Loss of skin integrity because of injury or illness may
      result acutely in substantial physiologic imbalance and ultimately in significant
      disability or even death. It is estimated that, in 1992, there were 35.2 million
      cases of significant skin loss (US data) that required major therapeutic
      intervention. Of these, approximately 7 million wounds become chronic. Regardless
      of the specific advanced wound care product, the ideal goal would be to
      regenerate tissues such that both the structural and functional properties of the
      wounded tissue are restored to the levels before injury. The advent of tissue
      engineered skin replacements revolutionized the therapeutic potential for
      recalcitrant wounds and for wounds that are not amenable to primary closure. This
      article will introduce the reader to the field of tissue engineering, briefly
      review tissue-engineered skin replacement from a historical perspective and then
      review current state-of-the-art concepts from our vantage point.

PMID- 17435789
TI  - Manipulation of host Kruppel-like factor (KLF) function by exotoxins from diverse
      bacterial pathogens.
AB  - Diverse pathogenic bacteria have developed similar mechanisms to subvert host
      cell responses. In this Progress article, we focus on bacterial virulence factors
      with different enzymatic activities that can increase the expression of the
      Kruppel-like factor (KLF) family of mammalian transcriptional regulators through
      their ability to modify the activity of a common host-cell target - the Rho
      protein family. By using a common virulence strategy, both Gram-negative and Gram
      positive pathogens exploit the KLF regulatory cascade to modulate nuclear factor
      kappaB activation, pro-inflammatory cytokine expression, actin cytoskeletal
      dynamics and phagocytosis.

PMID- 17435790
TI  - DNA replication initiation: mechanisms and regulation in bacteria.
AB  - In all organisms, multi-subunit replicases are responsible for the accurate
      duplication of genetic material during cellular division. Initiator proteins
      control the onset of DNA replication and direct the assembly of replisomal
      components through a series of precisely timed protein-DNA and protein-protein
      interactions. Recent structural studies of the bacterial protein DnaA have helped
      to clarify the molecular mechanisms underlying initiator function, and suggest
      that key structural features of cellular initiators are universally conserved.
      Moreover, it appears that bacteria use a diverse range of regulatory strategies
      dedicated to tightly controlling replication initiation; in many cases, these
      mechanisms are intricately connected to the activities of DnaA at the origin of
      replication. This Review presents an overview of both the mechanism and
      regulation of bacterial DNA replication initiation, with emphasis on the features
      that are similar in eukaryotic and archaeal systems.

PMID- 17435791
TI  - The tad locus: postcards from the widespread colonization island.
AB  - The Tad (tight adherence) macromolecular transport system, which is present in
      many bacterial and archaeal species, represents an ancient and major new subtype
      of type II secretion. The tad genes are present on a genomic island named the
      widespread colonization island (WCI), and encode the machinery that is required
      for the assembly of adhesive Flp (fimbrial low-molecular-weight protein) pili.
      The tad genes are essential for biofilm formation, colonization and pathogenesis
      in the genera Aggregatibacter (Actinobacillus), Haemophilus, Pasteurella,
      Pseudomonas, Yersinia, Caulobacter and perhaps others. Here we review the
      structure, function and evolution of the Tad secretion system.

PMID- 17435792
TI  - The role of ecological theory in microbial ecology.
AB  - Microbial ecology is currently undergoing a revolution, with repercussions
      spreading throughout microbiology, ecology and ecosystem science. The rapid
      accumulation of molecular data is uncovering vast diversity, abundant
      uncultivated microbial groups and novel microbial functions. This accumulation of
      data requires the application of theory to provide organization, structure,
      mechanistic insight and, ultimately, predictive power that is of practical value,
      but the application of theory in microbial ecology is currently very limited.
      Here we argue that the full potential of the ongoing revolution will not be
      realized if research is not directed and driven by theory, and that the
      generality of established ecological theory must be tested using microbial
      systems.

PMID- 17435793
TI  - Non-steroidal anti-inflammatory drugs increase insulin release from beta cells by
      inhibiting ATP-sensitive potassium channels.
AB  - BACKGROUND AND PURPOSE: Some non-steroidal anti-inflammatory drugs (NSAIDs)
      incidentally induce hypoglycemia, which is often seen in diabetic patients
      receiving sulphonylureas. NSAIDs influence various ion channel activities, thus
      they may cause hypoglycemia by affecting ion channel functions in insulin
      secreting beta cells. This study investigated the effects of the NSAID
      meclofenamic acid (MFA) on the electrical excitability and the secretion of
      insulin from pancreatic beta cells. EXPERIMENTAL APPROACH: Using patch clamp
      techniques and insulin secretion assays, the effects of MFA on the membrane
      potential and transmembrane current of INS-1 cells, and insulin secretion were
      studied. KEY RESULTS: Under perforated patch recordings, MFA induced a rapid
      depolarization in INS-1 cells bathed in low (2.8 mM), but not high (28 mM)
      glucose solutions. MFA, as well as acetylsalicylic acid (ASA) and flufenamic acid
      (FFA), excited the cells by inhibiting ATP-sensitive potassium channels (K(ATP)).
      In whole cell recordings, K(ATP) conductance consistently appeared when
      intracellular ATP was diluted. Intracellular glibenclamide prevented the
      development of K(ATP) activity, whereas intracellular MFA had no effect. At low
      glibenclamide concentrations, MFA induced additional inhibition of the K(ATP)
      current. Live cell Ca(2+) imaging displayed that MFA elevated intracellular
      Ca(2+) at low glucose concentrations. Furthermore, MFA dose-dependently increased
      insulin release under low, but not high, glucose conditions. CONCLUSIONS AND
      IMPLICATIONS: MFA blocked K(ATP) through an extracellular mechanism and thus
      increased insulin secretion. As some NSAIDs synergistically inhibit K(ATP)
      activity together with sulphonylureas, the risk of NSAID-induced hypoglycemia
      should be considered when glucose-lowering compounds are administered.

PMID- 17435794
TI  - Irsogladine maleate potentiates the effects of nitric oxide on activation of cAMP
      signalling pathways and suppression of mesangial cell mitogenesis.
AB  - BACKGROUND AND PURPOSE: Deficiency in nitric oxide (NO) is a major factor leading
      to deterioration and progression of certain glomerular diseases. Agents enhancing
      NO availability and potentiality are renoprotective. Irsogladine maleate (IM), an
      anti-ulcer drug, is reported to improve gastric blood flow via NO-dependent
      mechanisms. We, therefore, asked whether and how IM interacted with NO on
      glomerular mesangial cells. EXPERIMENTAL APPROACH: Mesangial cells were exposed
      to IM and NO donors. Activation of cAMP signalling pathways was assessed by
      intracellular cAMP, phosphorylation of VASP, activation of the cAMP response
      element (CRE) and expression of CRE-regulated proteins. KEY RESULTS: IM alone did
      not affect cell proliferation. However, it greatly enhanced the growth-inhibitory
      effect of NO donor S-nitroso-N-acetylpenicillamine (SNAP). IM acted
      synergistically with NO on suppression of mitogen-activated protein kinase
      activation, induction of gap junction protein connexin43, increase of
      intracellular cAMP, and phosphorylation of VASP. With the use of the CRE-SEAP
      based reporting system, IM and SNAP cooperatively activated cAMP response
      elements (CRE). A similar activation of cAMP was induced by IM with two different
      NO donors, the sGC activator Bay 41-2272 and the cGMP analogue 8-bromo-cGMP. The
      effects of SNAP and IM on cAMP activation were mimicked by phosphodiesterase 3
      (PDE3) and PDE4 inhibitors. In addition, IM markedly augmented cytokine-induced
      expression of iNOS, production of NO and activation of CRE. CONCLUSION AND
      IMPLICATIONS: The effects of NO were greatly potentiated by IM through
      synergistic activation of cAMP pathway. Combined therapy with IM and NO may be
      developed for certain renal diseases.

PMID- 17435795
TI  - Anandamide and NADA bi-directionally modulate presynaptic Ca2+ levels and
      transmitter release in the hippocampus.
AB  - BACKGROUND AND PURPOSE: Inhibitory CB(1) cannabinoid receptors and excitatory
      TRPV(1) vanilloid receptors are abundant in the hippocampus. We tested if two
      known hybrid endocannabinoid/endovanilloid substances, N-arachidonoyl-dopamine
      (NADA) and anandamide (AEA), presynapticaly increased or decreased intracellular
      calcium level ([Ca(2+)](i)) and GABA and glutamate release in the hippocampus.
      EXPERIMENTAL APPROACH: Resting and K(+)-evoked levels of [Ca(2+)](i) and the
      release of [(3)H]GABA and [(3)H]glutamate were measured in rat hippocampal nerve
      terminals. KEY RESULTS: NADA and AEA per se triggered a rise of [Ca(2+)](i) and
      the release of both transmitters in a concentration- and external Ca(2+)
      dependent fashion, but independently of TRPV(1), CB(1), CB(2), or dopamine
      receptors, arachidonate-regulated Ca(2+)-currents, intracellular Ca(2+) stores,
      and fatty acid metabolism. AEA was recently reported to block TASK-3 potassium
      channels thereby depolarizing membranes. Common inhibitors of TASK-3, Zn(2+),
      Ruthenium Red, and low pH mimicked the excitatory effects of AEA and NADA,
      suggesting that their effects on [Ca(2+)](i) and transmitter levels may be
      attributable to membrane depolarization upon TASK-3 blockade. The K(+)-evoked
      Ca(2+) entry and Ca(2+)-dependent transmitter release were inhibited by nanomolar
      concentrations of the CB(1) receptor agonist WIN55212-2; this action was
      sensitive to the selective CB(1) receptor antagonist AM251. However, in the low
      micromolar range, WIN55212-2, NADA and AEA inhibited the K(+)-evoked Ca(2+) entry
      and transmitter release independently of CB(1) receptors, possibly through direct
      Ca(2+) channel blockade. CONCLUSIONS AND IMPLICATIONS: We report here for hybrid
      endocannabinoid/endovanilloid ligands novel dual functions which were
      qualitatively similar to activation of CB(1) or TRPV(1) receptors, but were
      mediated through interactions with different targets.

PMID- 17435796
TI  - Characterization of a novel ATP-sensitive K+ channel opener, A-251179, on urinary
      bladder relaxation and cystometric parameters.
AB  - BACKGROUND AND PURPOSE: ATP-sensitive K(+) channels (K(ATP)) play a pivotal role
      in contractility of urinary bladder smooth muscle. This study reports the
      characterization of 4-methyl-N-(2,2,2-trichloro-1-(3-pyridin-3
      ylthioureido)ethyl)benzamide (A-251179) as a K(ATP) channel opener. EXPERIMENTAL
      APPROACH: Glyburide-sensitive membrane potential, patch clamp and tension assays
      were employed to study the effect of A-251179 in vitro. The in vivo efficacy of A
      251179 was characterized by suppression of spontaneous contractions in obstructed
      rat bladder and by measuring urodynamic function of urethane-anesthetized rat
      models. KEY RESULTS: A-251179 was about 4-fold more selective in activating SUR2B
      Kir6.2 derived K(ATP) channels compared to those derived from SUR2A-Kir6.2. In
      pig bladder smooth muscle strips, A-251179 suppressed spontaneous contractions,
      about 27- and 71-fold more potently compared to suppression of contractions
      evoked by low-frequency electrical stimulation and carbachol, respectively. In
      vivo, A-251179 suppressed spontaneous non-voiding bladder contractions from
      partial outlet-obstructed rats. Interestingly, in the neurogenic model where
      isovolumetric contractions were measured by continuous transvesical cystometry, A
      251179 at a dose of 0.3 micromol kg(-1), but not higher, was found to increase
      bladder capacity without affecting either the voiding efficiency or changes in
      mean arterial blood pressure. CONCLUSIONS AND IMPLICATIONS: The thioureabenzamide
      analog, A-251179 is a potent novel K(ATP) channel opener with selectivity for
      SUR2B/Kir6.2 containing K(ATP) channels relative to pinacidil. The
      pharmacological profile of A-251179 is to increase bladder capacity and to
      prolong the time between voids without affecting voiding efficiency and
      represents an interesting characteristic to be explored for further
      investigations of K(ATP) channel openers for the treatment of overactive bladder.

PMID- 17435797
TI  - Inhibition of cyclooxygenases by dipyrone.
AB  - BACKGROUND AND PURPOSE: Dipyrone is a potent analgesic drug that has been
      demonstrated to inhibit cyclooxygenase (COX). In contrast to classical COX
      inhibitors, such as aspirin-like drugs, dipyrone has no anti-inflammatory effect
      and a low gastrointestinal toxicity, indicating a different mode of action. Here,
      we aimed to investigate the effects of dipyrone on COX. EXPERIMENTAL APPROACH:
      The four major metabolites of dipyrone, including the two pharmacologically
      active metabolites, 4-methyl-amino-antipyrine (MAA) and amino-antipyrine (AA),
      were used to characterise their binding to COX and haem as well as their effects
      on the biochemical properties of COX. Mass spectrometry, UV and visible
      photometry were used to study binding and prostaglandin production. Levels of
      anti-oxidant enzymes were assessed by Western blotting. KEY RESULTS: The
      pharmacologically active metabolites of dipyrone, MAA and AA, did not inhibit COX
      activity in vitro like classical COX inhibitors, but instead redirected the
      prostaglandin synthesis, ruling out inhibition of COX through binding to its
      active site. We found that MAA and AA formed stable complexes with haem and
      reacted with hydrogen peroxide in presence of haem, ferrous ions (Fe(2+)) or COX.
      Moreover, MAA reduced Fe(3+) to Fe(2+) and accordingly increased lipid
      peroxidation and the expression of anti-oxidant enzymes in cultured cells and in
      vivo. CONCLUSIONS AND IMPLICATIONS: Our data suggest that the pharmacologically
      active metabolites of dipyrone inhibit COX activity by sequestering radicals
      which initiate the catalytic activity of this enzyme or through the reduction of
      the oxidative states of the COX protein.

PMID- 17435798
TI  - Hepatoprotective role of PXR activation and MRP3 in cholic acid-induced
      cholestasis.
AB  - BACKGROUND AND PURPOSE: Activation of the pregnane X receptor (PXR) has been
      shown to protect against cholestatic hepatotoxicity. As PXR alters the expression
      of numerous hepatic bile acid transporters, we sought to delineate their
      potential role in hepatoprotection. EXPERIMENTAL APPROACH: Wild-type (PXR+/+) and
      PXR-null (PXR-/-) mice were fed a 1% cholic acid (CA) diet with or without the
      PXR activator, PCN. Liver function was assessed along with the corresponding
      changes in hepatic gene expression. KEY RESULTS: CA administration caused
      significant hepatotoxicity in PXR+/+ mice and was associated with induction of
      several FXR and PXR regulated genes, which encode for bile acid transport and
      metabolizing proteins. Compared to CA alone, co-administration of PCN to CA-fed
      PXR+/+ mice significantly decreased hepatotoxicity and was associated with
      induction of MRP3 mRNA as well as CYP3A11 mRNA and functional activity.
      Unexpectedly, PXR-/- mice, which expressed significantly higher basal and CA
      induced levels of MRP2, MRP3, OSTalpha, OSTbeta, OATP2 and CYP3A11, were
      dramatically less sensitive to CA hepatotoxicity than PXR+/+ mice. CONCLUSIONS:
      Protection of PXR+/+ mice against CA-induced hepatotoxicity by PCN is associated
      with the induction of MRP3 and CYP3A11 expression. Resistance against CA-induced
      hepatotoxicity in PXR-/- mice may result from higher basal and induced expression
      of bile acid transporters, particularly MRP3. These findings emphasize the
      importance of transport by MRP3 and metabolism as major protective pathways
      against cholestatic liver injury.

PMID- 17435799
TI  - [Right to a good death].

PMID- 17435800
TI  - [Norwegian heart transplantation].

PMID- 17435801
TI  - [Tuberous sclerosis].

PMID- 17435802
TI  - [Carotid surgery prevents stroke].

PMID- 17435803
TI  - [Surgeon's glove--a love story].

PMID- 17435804
TI  - [The risk of surgical glove perforations].
AB  - BACKGROUND: The increasing prevalence of blood-borne viral diseases has drawn
      attention to the barrier between the surgical personnel's hands and the patients
      body fluids during surgery. At present, the typical practice is to use double
      gloving in orthopaedic surgery, and single gloving in other types of surgery. The
      main purpose of our study was to estimate and compare the perforation risk in
      different categories of surgery. MATERIAL AND METHODS: In a series of 655
      surgical operations covering 5 main categories of surgery, all detected glove
      perforations were recorded and analysed. RESULTS: Perforations were found in 203
      out of 655 operations (31%). The observed perforation frequency was 44.5% in
      gastrointestinal surgery, 34.7% in orthopaedic surgery, 31.1% in gynaecology,
      18.6% in vascular surgery and 9.2% in general surgery. In some subcategories, the
      frequencies were even higher. INTERPRETATION: In several categories of surgery,
      we found high perforation frequencies. Perforations in single gloves are often
      not detected during operations. This may increase the risk of transmission of
      blood-borne infections, particularly because the time of exposure may be long.
      Double indicator gloves make the intra-operative detection of perforations
      easier. Also double gloving is known to significantly reduce the perforation
      risk. The use of double indicator gloves is recommended in all categories of
      surgery.

PMID- 17435805
TI  - [Improved hand hygiene through simple interventions].
AB  - BACKGROUND: On the basis of new National Guidelines for Hand Hygiene, a project
      was started in 2004 in a medical ward at Haukeland University Hospital. The aims
      were to improve the personnel's compliance with hand hygiene guidelines and to
      transfer from soap hand wash to a disinfectant alcohol-based hand rub. MATERIAL
      AND METHODS: Two interventions were implemented: information about hand hygiene
      and increased availability of alcohol-based hand rub. The personnel's hand
      hygiene performance was recorded through 3 questionnaire-based interviews. The
      effect was assessed with a paired t-test, by comparing scores 2 and 9 months
      after the interventions with those before the interventions. Effect was also
      measured as changes in expenditure on alcohol-based hand rub compared with those
      for hand soap. RESULTS: Significant improvements were found for hand hygiene
      before (p = 0.02) and after (p = 0.01) direct contact with patients, after
      contact with objects near the patient (p = 0.002), before medicine distribution
      (p = 0.007) and for two subscores when evaluated after 2 months. The 9-month
      evaluation maintained most of these results, and for some questions the results
      improved. The expenditure on hand soap decreased, while the expenditure on
      alcohol-based hand rub increased significantly from 16 to 26 L/1000 treatment
      days (p = 0.02). There was little change in the total consumption of hand soap
      and alcohol-based hand rub. INTERPRETATION: Information about hand hygiene and
      increased availability of alcohol-based hand rub led to improved hand hygiene at
      all levels of staff.

PMID- 17435806
TI  - [Survival after heart transplantation in Norway].
AB  - BACKGROUND: Heart transplantation has been a treatment option in Norway for
      selected patients with terminal congestive heart failure since 1983. The number
      of transplants is limited by donor availability. Few Norwegian doctors are aware
      of the challenges to be expected in taking care of heart transplant recipients.
      In the present paper we therefore present our experience so far. MATERIAL AND
      METHODS: We have followed individuals within our patient cohort for up to 22
      years. The cohort consists of 522 patients (mean age 48.8 years +/- 13.6),
      somewhat unequally distributed from various parts of the country, reflecting the
      local referring practice. We have a complete overview of the patients who are
      partly followed up locally, but come to a control at least once a year at our
      hospital. RESULTS AND INTERPRETATION: Mean survival in these patients is 12
      years. With an expected survival of less than one year without transplantation,
      these are strong results that compare well with international figures. Patients
      younger than 50 years at transplantation have the best prognosis regardless of
      donor age, while the combination of patients older than 50 years and donor above
      35 years have the poorest chance of survival. However, patients are disposed to
      various severe complications. Initially after transplantation acute rejection,
      unspecific graft failure and infections are a threat; while complications such as
      chronic graft sclerosis, renal failure and cancer are complications that appear
      over time. To optimise results, life-long regular follow up is necessary.

PMID- 17435807
TI  - [Tuberous sclerosis complex].
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) as a syndrome has not previously
      been reviewed in the Journal of the Norwegian Medical Association. TSC is a
      genetic disorder characterised by growth of tumours in many organs; most often in
      the brain, heart, kidneys and skin. The diagnosis is based on revised clinical
      criteria approved at a consensus conference in 1998. MATERIAL AND METHOD: This is
      a short summary of the current knowledge about tuberous sclerosis complex, based
      on relevant literature and our own clinical experience; with special emphasis on
      diagnosis, treatment, and how to follow up the patients and their relatives.
      RESULTS AND INTERPRETATION: TSC is an autosomal dominant inherited syndrome.
      Mutations in tumour suppressor genes on chromosomes 9( TSC1: ) or 16( TSC2:),
      give rise to different phenotypic expressions. The common denominator is a
      tendency towards increased cell growth due to inactivation of the gene products
      hamartin (chromosome 9) or tuberin (chromosome 16). It is assumed that most cases
      are caused by new somatic mutations. Sneaking symptoms from affected organs
      necessitate close surveillance of the patients. Both patients and their relatives
      are in need of information and guidance, both in clinical and genetic matters. In
      Norway, a centre of competence within TSC has been established to meet such
      needs.

PMID- 17435808
TI  - [Rock music and hearing disorders].
AB  - BACKGROUND: Continued exposition to loud noise is a well-known risk factor for
      development of various hearing disorders; rock musicians are especially
      vulnerable. The aim of this paper was to get an overview of hearing loss,
      tinnitus and hyperacusis among rock musicians. MATERIAL AND METHOD: Medline was
      systematically searched, using combinations of the terms "hearing", "rock music",
      "tinnitus" and "hyperacusis". RESULTS AND INTERPRETATION: Seven publications
      concerning hearing of rock musicians were identified. Permanent hearing loss
      occurred in 20% (mean) of the rock musicians; the prevalence varied from 5 to
      41%. Tinnitus and hyperacusis appear significantly more often in rock musicians
      than in non-musicians. Rock musicians have increased resistance against loud
      music and exposure over time is protective towards hearing loss. Further research
      is needed to assess rock music's impact on musicians' hearing.

PMID- 17435809
TI  - [Life-prolonging treatment--an analysis of two cases].
AB  - BACKGROUND: Life-prolonging treatment is associated with many difficult ethical
      considerations, especially when such treatment is withdrawn. MATERIAL AND
      METHODS: Two cases are presented where life-prolonging treatment played a key
      part. The two were analyzed by using a 5-point checklist that the Clinical Ethics
      Committee at Haukeland University Hospital has developed. We were visiting
      students at a neonatal department and an intensive care unit, we read relevant
      literature and consulted experienced doctors. RESULTS AND INTERPRETATIONS: We saw
      that well-founded decisions were made for each of the two patients studied; this
      is in accordance with our experience from hospital departments. We believe that
      continuous technological advances in medicine require doctors to make more
      decisions involving ethical considerations now than before, but that they are not
      necessarily better equipped to do so. There is a need to improve integration of
      medical ethics in the education of medical students, and for doctors to have more
      knowledge about existing ethics regulations.

PMID- 17435810
TI  - [Roseroot--statements and documentation].

PMID- 17435811
TI  - [How to diagnose acute stroke?].
AB  - BACKGROUND: Stroke is a treatable disease that presents with rapidly developing
      clinical symptoms. Treatment depends on early diagnosis and transportation as
      quickly as possible to a treating hospital. Delayed diagnosis or misdiagnosis of
      stroke is common. Criteria for clinical diagnosis of stroke are needed. MATERIAL
      AND METHODS: Based on a review of the literature found in Medline this article
      proposes tools and criteria for diagnosis of a probable stroke before and after
      hospitalization. RESULTS AND INTERPRETATION: The diagnosis depends on rapidly
      developing symptoms or new symptoms on awakening. Symptoms associated with a high
      probability of stroke are acute unilateral paresis, lateralisation of symptoms to
      one hemisphere, high neurological score on NIH and symptoms corresponding to a
      certain vascular territory. Simple screening tools increase the pre-hospital
      probability of stroke. In hospital a definite diagnosis is based upon CT or MRI
      findings. Diffusion-weighted MRI is highly sensitive in acute ischemic stroke.
      The diagnosis is considered definite when clinical symptoms correspond with MRI
      findings. There are still no biochemical markers available to diagnose acute
      stroke. Diagnostic instruments improve diagnostic accuracy of acute stroke.

PMID- 17435812
TI  - [Atherosclerosis and cerebral infarction].
AB  - BACKGROUND: Approximately half of all cerebral infarctions are caused by artery
      to-artery emboli from atherosclerotic plaques in the aorta and pre- or
      intracranial arteries. This review article presents an update on the development
      of atherosclerotic plaques, and discusses the diagnostic and therapeutic
      implications of new pathophysiological knowledge of atherosclerosis in relation
      to cerebral infarction. MATERIAL AND METHODS: The article is based on our own
      clinical-neurological experience and publications mainly on intima-media
      thickness (IMT) and ultrasound in the diagnosis of cerebrovascular disease,
      identified through a Medline search. RESULTS: Unstable plaques have a thin and
      vulnerable capsule, inflammatory cells, high fat content and often intra-plaque
      bleeding. Calcium deposition and organized fibrous tissue have a stabilizing
      effect. The development of atherosclerosis and biological characteristics of
      plaques can be explained by known vascular risk factors and genetic disposition.
      Ultrasound examination of the aorta and pre-cerebral arteries can be used to
      assess the degree of atherosclerosis and to provide important information
      regarding patients' risk of cerebrovascular disease. INTERPRETATION: New
      knowledge regarding the pathophysiology of atherosclerosis can improve prediction
      of a patient's risk for ischemic stroke. This forms the basis for a better and
      more individualized prophylactic treatment of cerebrovascular disease.

PMID- 17435813
TI  - [Heart disease and stroke].
AB  - BACKGROUND: Heart diseases and stroke are the most important causes of death and
      disability in the Western world. This article gives a review of the relationship
      between heart diseases and stroke, and gives advice for clinical management of
      patients with a suspected cardioembolic stroke. MATERIAL AND METHODS: The article
      is based on books and articles found through a search in Medline. RESULTS AND
      INTERPRETATION: Most cases of heart disease and stroke are caused by
      atherosclerosis, and the two diseases have much in common with regards to risk
      factors, treatment and prognosis. Heart disease may also be a direct cause of
      stroke. About one in four cerebral infarctions are due to embolism from the heart
      to the brain, mainly because of atrial fibrillation, but also because of diseases
      such as acute myocardial infarction, dilated cardiomyopathy and prosthetic heart
      valves (cardioembolic stroke). Stroke can also be caused by a cardiogenic fall in
      blood pressure in patients with stenoses in pre- or intracerebral arteries
      (haemodynamic stroke). Patients with symptoms of atherosclerosis in one artery
      system should be treated as if they have a high risk of developing symptoms from
      other artery systems. The possibility of a cardiac embolic source should always
      be considered in patients with acute brain infarctions.

PMID- 17435814
TI  - [Transitory ischemic attack].
AB  - BACKGROUND: Neurological symptoms rapidly resolve after a transitory ischemic
      attack (TIA). Diffusion-weighted MRI and new clinical studies have greatly
      increased our understanding of the pathophysiology and clinical impact of TIA.
      This review presents an update on pathophysiology, symptoms, diagnosis and
      treatment of TIA. MATERIAL AND METHODS: This article is based on our clinical
      experience, European guidelines for acute cerebrovascular disease and recent
      medical literature found by searching Medline. RESULTS AND INTERPRETATION: TIA is
      a warning of a potential cerebrovascular disaster. About 10-13% of TIA patients
      will have a stroke within a few months, half of them within a few days. A more
      urgent approach to TIA diagnosis and treatment should prevent many strokes and
      deaths. All TIA patients should therefore be referred as an emergency to a stroke
      unit.

PMID- 17435815
TI  - [Operative and endovascular treatment of carotis stenosis--when is it
      indicated?].
AB  - BACKGROUND: Stroke is the most common cause of disability in Norway. Most strokes
      are ischemic, and 25-30% are caused by emboli from atherosclerotic plaques in pre
      cerebral arteries. The aim of this study was to review the literature on
      effectiveness of stroke prevention by surgical and endovascular treatment of
      carotid bifurcation stenoses. MATERIAL AND METHODS: Search of the PubMed and
      Cochrane Library. Relevant textbook chapters and personal experience have also
      supported the evaluation. RESULTS AND INTERPRETATION: Prevention of stroke by
      carotid endarterectomy is documented in several large randomised controlled
      trials. For carotid stenoses with reduced diameters of more than 50%, a
      significant reduction of 5-year stroke risk is achieved with surgery and best
      medical treatment, compared to best medical treatment alone. The benefit is
      greatest with symptomatic stenoses, especially if surgery is performed shortly
      after onset of symptoms. Patients with transient ischemic attack (TIA), minor
      stroke or amaurosis fugax should without delay be referred to an ultrasound
      examination of the carotid. Surgery as soon as possible is indicated if > 70%
      stenosis is found, and for men also with moderate stenoses (50-69%). The benefit
      is less pronounced for women with moderate stenosis and they should be considered
      individually. In asymptomatic patients, surgery reduces the 5-year stroke risk
      from 11.8 to 6.4%. The indication for surgery in asymptomatic patients must be
      balanced against age, co-morbidity, and the quality of surgery at each centre. A
      low operative morbidity is a prerequisite. No comparable evidence exists for
      endovascular treatment, and it is recommended that patients eligible for stent
      treatment are included in ongoing randomised trials comparing stent treatment and
      endarterectomy.

PMID- 17435816
TI  - [Medicine and psychiatry--in part and divided?].

PMID- 17435817
TI  - [When the time is in].

PMID- 17435820
TI  - [Methadone and arrhythmia--final comment].

PMID- 17435825
TI  - [Surface anatomy in Greek sculpture].

PMID- 17435827
TI  - [As a wandering in psychiatry of the past].

PMID- 17435830
TI  - Fas-mediated apoptosis is suppressed by calf serum in cultured bovine luteal
      cells.
AB  - Calf serum (CS) is a common supplement used in cell culture. It has been
      suggested that CS contains substances protecting cells against apoptosis. To
      examine whether a culture system including CS is appropriate for studying
      apoptosis in bovine luteal cells, we examined the influence of CS on the
      expression of Fas, bcl-2 and bax gene. Since progesterone (P(4)) is known to be
      an anti-apoptotic factor in bovine luteal cells, the present study was carried
      out to examine the P(4) effect on apoptosis. Bovine mid-luteal cells were exposed
      to Fas ligand (Fas L) in the presence or in the absence of P(4) antagonist
      (onapristone, OP) in a basal medium (BM) containing 5% CS (BM-CS) or BM
      containing 0.1% BSA (BM-BSA). Although Fas L alone, OP alone or Fas L plus OP did
      not show any cytotoxic effect on the cells cultured in BM-CS, administration of
      OP or OP in combination with Fas L resulted in the killing of 30% and 55% of the
      cells cultured in BM-BSA medium, respectively (p<0.05). Concomitantly, CS
      inhibited bax mRNA expression and stimulated bcl-2 expression in the cells
      (p<0.05). Moreover, in the cells cultured with BM-CS, Fas mRNA expression was
      smaller than that of cells incubated in BM-BSA medium (p<0.05). The overall
      results suggest that CS suppressed Fas-mediated cell death in cultured bovine
      luteal cells by promoting the ratio of bcl-2 to bax expression and by inhibiting
      Fas expression. Therefore, it may be suggested that CS contains such anti
      apoptotic substances (growth factors) amplifying the cell survival pathways in
      the bovine corpus luteum (CL) in vitro.

PMID- 17435831
TI  - Long form of leptin receptor gene and protein expression in the porcine ovary
      during the estrous cycle and early pregnancy.
AB  - Leptin, a hormone secreted by adipocytes, plays an important role in the
      regulation of metabolism and reproduction. The effect of leptin is mediated
      mainly via the long isoform of the leptin receptor (OB-Rb). Expression of leptin
      and its receptor has been identified in the central nervous system (hypothalamus,
      pituitary) and reproductive tract (uterus, ovary and placenta) in prepubertal
      gilts. Therefore, in the present study, the porcine OB-Rb expression was examined
      by a semiquantitative reverse transcription polymerase chain reaction (RT-PCR),
      in situ hybridization and Western blotting in the corpus luteum (CL) and ovarian
      stroma (OS) during the luteal phase of the estrous cycle (days 10-12 and 14-16)
      and two stages of early pregnancy (days 14-16 and 30-32). The OB-Rb gene
      expression in both ovarian structures was higher during early pregnancy in
      comparison to the mid- and late-luteal phase of the estrous cycle. Significant
      differences in OB-Rb gene expression between the two periods of the pregnancy
      were observed only in OS. The results of in situ hybridization are generally
      supported by data of semiquantitative RT-PCR. The CL expression of leptin
      receptor protein was significantly lower during early pregnancy compared to the
      cycle. In OS, the OB-Rb protein content was higher during pregnancy compared to
      the late-luteal phase of the estrous cycle. In summary, the obtained results
      indicate that leptin may participate in the control of pig reproduction at the
      ovarian level and have a direct effect on the ovary during both, the luteal phase
      of the cycle and early pregnancy. Moreover, changes in OB-Rb gene and protein
      expression in ovarian structures strongly suggest that their sensitivity to
      leptin varies throughout the luteal phase of the cycle and early pregnancy.

PMID- 17435832
TI  - Diabetes alters the mRNA expression of insulin-like growth factors and their
      receptors in the mouse fallopian tube and uterus during the preimplantation
      stages.
AB  - The possible role of insulin-like growth factors (IGFs) and their receptors
      (IGFRs) in the pathogenesis of diabetic embryopathy was investigated. Sexually
      mature female ICR mice of 6-8 weeks old were made diabetic by a single
      intraperitoneal injection with 200 mg/kg streptozotocin ten days prior to mating.
      Fallopian tubes and uterine tissues were obtained from the superovulated diabetic
      and normal mice 48, 72 and 96 hours following human chorionic gonadotropin (hCG)
      injection. The mRNA expression of IGF-1 and IGF-2 as well as their receptors was
      determined in the tissues using Real-time Polymerase Chain Reaction (Real-time
      PCR). The mRNA expression of IGF-1 in the fallopian tube and uterus of the
      diabetic mice was significantly lower 72 and 96 hours after hCG treatment,
      respectively, as compared to the controls. The mRNA expression of IGF-1R at 96
      hours post-hCG treatment was significantly higher in the fallopian tube and lower
      in the uterus of the diabetic mice as compared to the controls. The mRNA
      expression IGF-2 in the fallopian tube was significantly higher 48 and 96 hours
      after hCG treatment, but was lower in the uterus of diabetic mice 96 hours after
      hCG treatment as compared to controls. The mRNA expression of IGF-2R in the
      diabetic mice was significantly higher 48 and 96 hours (the fallopian tube) and
      48 hours (uterus) after hCG treatments as compared to the controls. In
      conclusion, an alteration in mRNA expression of IGFs and their receptors in the
      diabetic mice as observed in this study could possibly result in diabetic
      embryopathy.

PMID- 17435833
TI  - The effect of stress on the expression of GnRH and GnRH receptor genes in the
      discrete regions of the hypothalamus and pituitary of anestrous ewes.
AB  - Using the Reverse Transcription-Polymerase Chain Reaction (RT-PCR) technique, the
      gonadotropin releasing-hormone (GnRH) mRNA and GnRH receptor (GnRH-R) mRNA were
      analyzed in the preoptic area (POA), anterior (AH) and ventromedial (VM)
      hypothalamus, stalk/median eminence (SME) and anterior pituitary gland (AP) of
      anestrous ewes subjected to short or prolonged footshock stimulation. No GnRH
      gene expression was detected in the SME and AP. The comparable levels of GnRH
      mRNA were found in the POA, AH and VM in control ewes. Short and prolonged
      footshock stimulation significantly increased GnRH mRNA in all analyzed tissue.
      The highest responses in GnRH mRNA to the short stress occurred in the POA
      whereas to the prolonged stress in the POA and VM. In non-stressed ewes the GnRH
      R mRNA were detected in tissue continuum throughout the POA, AH, VM, SME and AP.
      The highest concentration of GnRH-R mRNA was detected in the SME. Short as well
      as prolonged stress stimuli caused an increase in GnRH-R mRNA levels in all
      analyzed tissue. The highest responses in GnRH-R mRNA expression were found in
      the VM. In spite of profound up-regulation of GnRH mRNA and GnRH-R mRNA under the
      short and prolonged stress conditions, the increase of luteinizing hormone (LH)
      secretion was noted only during acute stress. It is suggested that the increase
      of expression of GnRH and GnRH-R genes in anestrous ewes are not directly related
      to GnRH level and GnRH-R activity.

PMID- 17435834
TI  - Effect of steroids on basal and LH-stimulated prostaglandins F(2alpha) and E(2)
      release and cyclooxygenase-2 expression in cultured porcine endometrial stromal
      cells.
AB  - Ovarian steroids modulate uterine receptivity in domestic species. Luteinizing
      hormone (LH) stimulates prostaglandin (PG)F(2alpha) release from the porcine
      endometrium. However, the combined action of LH and steroids on PGs secretion has
      not yet been studied in pigs. The aim of the present study was to examine the
      effect of estradiol (E(2)) and progesterone (P(4)) on basal and LH-stimulated
      PGF(2alpha) and PGE(2) secretion and cyclooxygenase-2 (COX-2) protein expression
      in porcine endometrial stromal cells obtained on days 12-13 of the estrous cycle.
      Cells were cultured for 48 h in a medium containing charcoal-stripped newborn
      calf serum alone or supplemented with 10 nM E(2) and/or 50 nM P(4). Then, the
      cells were incubated for 6 h in the presence or absence of LH (20 ng/ml). Long
      exposure of stromal cells to steroids had no effect on PGF(2alpha) secretion, but
      PGE(2) release increased in the presence of E(2) plus P(4) (p<0.05). Pre
      incubation of cells with E(2) plus P(4) resulted in enhanced PGF(2alpha) (p<0.05)
      and PGE(2) (p<0.001) secretion. Moreover, LH increased PG(2alpha) secretion in
      control (p<0.05) and E(2)-treated stromal cells (p<0.01). LH tended (p=0.07) to
      elevate PGE(2) release only in cells pre-exposed to E(2) plus P(4). The
      expression of COX-2 protein was increased by LH (p<0.05), but not by steroids.
      These results confirm the stimulatory effect of LH on PGF(2alpha) secretion and
      COX-2 expression in porcine stromal cells before luteolysis. PG release from
      porcine endometrium seems to be controlled by ovarian steroids, however only E(2)
      treated-treated cells responded to LH.

PMID- 17435835
TI  - [Rheumatic diseases in the Corpus Hippocraticum].
AB  - Medicine of V and IV centuries B.C. attested in the Corpus Hippocraticum ascribes
      all diseases to the rheuma, i.e. the flux of humours into the body. This flux
      produces not only the rise of cold, hoarseness, cough, reddening, dropsy, but
      also arthritis, sciatica, gout.

PMID- 17435836
TI  - [Magnetic resonance imaging of the peripheral joints in psoriatic arthritis].
AB  - OBJECTIVE: Magnetic resonance imaging (MRI) has been widely used for the
      evaluation of rheumatoid arthritis (RA), with only a minority of studies
      considering other types of arthritis. This review is concerned with an evaluation
      of the MRI appearance of peripheral joints in psoriatic arthritis (PsA). METHODS:
      A Medline search was performed to identify all publications from the years 1985
      to 2006 concerning MRI of the peripheral joints and PsA. Additional papers were
      retrieved by scanning the references to the Medline-listed articles. Articles
      written in English, French, German, and Italian were included. RESULTS: Most
      papers studied the hand and wrist, and only few of them were concerned with the
      knee, foot, temporomandibular joint, and elbow. Patients with PsA showed often,
      but not always, a pattern of joint inflammation which extended beyond the capsule
      into the extraarticular tissue. Bone oedema and erosions were less frequent than
      in RA. In particular, bone oedema at the entheseal junction was seen, especially
      in the knee. The degree of synovitis, assessed by dynamic MRI, was similar in PsA
      and RA. DISCUSSION: Data on MRI of the peripheral joints in PsA are scanty. Only
      few studies were specifically designed to evaluate the pattern of arthritis in
      PsA, with most information deriving from papers where different types of
      arthritis were considered together. An enthesis-related origin of PsA has been
      proposed in contrast to the primarily synovial inflammation of RA. This
      pathogenic interpretation is likely to be true, but does not explain all cases of
      PsA, and needs to be confirmed by further studies.

PMID- 17435837
TI  - [Vitamin D and fractures: a systematic review].
AB  - Vitamin D deficiency is a relevant problem particularly in south Europe and in
      over 65 year old subjects, that is often underestimated. Vitamin D deficiency
      represents a real medical emergency also for its role in the patho-physiology of
      muscular-skeletal diseases. Chronic vitamin D deficiency leads to severe bone and
      muscular outcomes including: osteoporosis, osteomalacia and proximal limb
      myopathy. These increase the risk of falling and fractures. The efficacy of
      vitamin D treatment in decreasing the fracture risk has been reporting in several
      studies. The negative results of some recent studies questioned the clinical
      vitamin D efficacy. However these studies have a number of methodological
      problems and even the interpretation of the results is questionable. In this
      paper we review all these aspects. This analysis permits to confirm that vitamin
      D treatment can be extremely cost-effective when given to people at high risk of
      deficiency. An acceptable compliance is obviously of critical importance.

PMID- 17435838
TI  - [Prevalence of anti-CCP antibodies in systemic sclerosis].
AB  - Joint involvement in systemic sclerosis (SSc) commonly occurs as arthralgias,
      while a true arthritis is less frequent. The most common arthritis developing in
      SSc is rheumatoid arthritis (RA) and its diagnosis may be misled by concomitant
      joint contracture or tendon sheath involvement due to SSc. Anti-citrullinated
      cyclic peptide (CCP) antibodies are an emerging tool to diagnose RA and have
      shown to be more specific than rheumatoid factor. We assessed the prevalence of
      anti-CCP antibodies in SSc patients and evaluated their sensitivity and
      specificity for associated RA. Searching for RF and anti-CCP antibodies and joint
      examination were carried out in sixty consecutive SSc patients. Hands and feet
      standard x-rays were performed in patients complaining with arthralgia and/or
      arthritis. Six out of sixty (10%) SSc patients had RA according to 1987 ARA
      revised criteria. Anti-CCP were detected in 5 patients (sensitivity 83%) and RF
      was present in all RA patients (sensitivity 100%). However, anti-CCP antibodies
      had a much higher specificity (94%) than RF (41%) for RA. Our study suggests that
      anti-CCP antibodies are a useful test to identify patients with SSc having also
      RA. This is crucial in the management of SSc because may allow an adequate
      therapy of RA and prevent further joint damage in patients who already have a
      poor quality of life.

PMID- 17435839
TI  - [Recurrent acute idiopathic pericarditis: rheumatologic therapy, autoantibodies
      and long term outcome].
AB  - OBJECTIVE: To evaluate therapy and rheumatologic aspects of recurrent acute
      idiopathic pericarditis (RAIP). METHODS: We studied 46 patients. We used non
      steroidal anti-inflammatory drugs (NSAIDs) at high dosage. We did not start
      corticosteroid: if already started, we planned a very slow tapering; 37 patients
      (80.4%) were treated with colchicine. We also assessed the frequency of ANA, anti
      SSA and Rheumatoid factor. RESULTS: With our protocol recurrences dropped from
      0.46 to 0.03 attacks/patient/month (p<0.00001) within 12 months and remained at
      the same level (0.024) till the end of the follow-up (mean 8 years). In the 37
      patients treated with colchicine recurrences dropped from 0.5 to 0.03 (p<0.0001)
      within 12 months, and in 9 patients not given colchicine from 0.27 to 0.045
      (p<0.005). When colchicine was used the decrease was significantly higher (0.47
      vs 0.23) (p<0.001). In 27 (58.7%) patients ANA were positive at a titre >1/80, in
      7 (15.2%) >1/160. Rheumatoid factor was positive in 7 (15.2%) and anti-SSA in 4
      (8.7%). During the follow-up 4 (8.7%) new diagnosis of Sjogren and 1 (2.2%) of
      Rheumatoid Arthritis were made. CONCLUSION: NSAIDs at high dosage, slow tapering
      of corticosteroid and colchicine are very effective in RAIP. The improvement is
      more dramatic in colchicine treated patients, but also other patients can achieve
      good control of the disease. The finding of ANA, anti-SSA and the new
      rheumatological diagnoses support the involvement of autoimmunity.

PMID- 17435840
TI  - [Anakinra, a recombinant human IL-1 receptor antagonist, in clinical practice.
      Outcome in 60 patients with severe rheumatoid arthritis].
AB  - OBJECTIVE: We evaluated both the efficacy and safety of anakinra in daily routine
      rheumatoid arthritis clinical practice. METHODS: We studied 60 cases, including
      patients with previous anti-TNFalpha exposure, treated with anakinra (100
      mg/daily s.c.) in combination with methotrexate (7.5-10 mg/week i.m.) or
      leflunomide (20 mg/die) in a two year observational study. Efficacy measures were
      assessed using the American College of Rheumatology (ACR) response criteria.
      Safety was evaluated according to a modified World Health Organization adverse
      reaction term dictionary. RESULTS: At week 14, ACR 20% response criteria have
      been fulfilled by 53 (91.3%) out of 58 patients, 51 (87.9%) of them achieving
      also an ACR 50%and 15 (25.8%) an ACR 70%response. Thirteen patients touched 102
      weeks of treatment: ACR 20% response was achieved in 92.3%, while ACR 50% and ACR
      70% were respectively found in 84.6% and 38.4% of the cases. The mean decrease in
      HAQ score was 0.38, p<0.001. Of the 16 patients who were previously treated with
      anti-TNFalpha blockers, 81.2% responded to anakinra. There was no significant
      difference in the ACR response between groups with and without previous anti
      TNFalpha exposure. Seventeen patients (28.3%) stopped anakinra because of side
      effects (5%) or failure to respond (23.3%). Only 4 cases of pulmonitis, of which
      2 have been hospitalised, and 1 case with tuberculosis (previously treated with
      infliximab) were observed. CONCLUSIONS: Our clinical experience confirms that
      anakinra is effective and safe in the treatment of rheumatoid arthritis. Anakinra
      seems also useful in patients with previous anti-TNFalpha blockers failures. Even
      though major adverse events were rare, clinicians should be aware of such a
      possibility.

PMID- 17435841
TI  - [Atherosclerosis in rheumatoid arthritis: the role of high-resolution B mode
      ultrasound in the measurement of the arterial intima-media thickness].
AB  - BACKGROUND: Patients with rheumatoid arthritis (RA) have a reduced life
      expectancy and high cardiovascular morbidity and mortality as compared to the
      general population. A number of possible factors for the atherogenesis in this
      disease have been described, such as homocysteine, altered serum levels of
      selected lipoproteins and treatment. Recent findings indicate that the systemic
      inflammation may contribute to the development of atherosclerosis and confer an
      additional risk for cardiovascular death among patients with RA. The aim of our
      study was to evaluate the ability of high resolution Bmode ultrasound and color
      Doppler to assess the existence of subclinical atherosclerosis in RA patients,
      measuring the intima-media thickness (IMT) and resistance index of the common
      carotid arteries. METHODS: Carotid IMT and carotid plaque were measured using
      high-resolution B-mode ultrasound in 40 patients with RA and 40 age- and sex
      matched healthy persons. We used color Doppler ultrasound to assess vascular
      damage of the common carotid arteries and the resistance index (RI) was
      determined by analysis of the spectral waveforms. Serum total cholesterol,
      triglycerides-density lipoprotein cholesterol, low-density lipoprotein
      cholesterol, rheumatoid factor, body mass index (BMI), visual analogue scale
      (VAS) were determined in patients and controls. C-reactive protein (CRP) and the
      DAS28 were used to measure systemic inflammation. RESULTS: Common carotid IMT
      were significantly higher (p=0.0009) in RA patients (0.83 +/- 0.23) compared with
      controls (0.66 +/- 0.22). In RA patients common carotid IMT was significantly
      correlated with serum total cholesterol (p=0.0008), low-density lipoprotein
      cholesterol (p=0.006), triglycerides (p=0.042), age (p=0.031) and disease
      duration (p=0.019). No significant correlation was found with clinical and
      laboratory parameters reflecting disease activity. The prevalence of plaques was
      higher in RA patients compared with controls (25% vs 12.5%). There was no
      significant difference in color Doppler findings, and in particular in RI,
      between patients and controls. CONCLUSIONS: Our results confirm an accelerated
      atherosclerosis, as shown by increased common carotid IMT, in patients with RA
      compared with controls and it is related mainly to lipid levels. High-resolution
      B-mode ultrasound may be considered a promising, sensitive and non invasive tool
      for assessing the existence of subclinical atherosclerosis in RA patients.

PMID- 17435842
TI  - [Long-term evaluation of infliximab in the treatment of persistently active
      juvenile idiopathic arthritis refractory to conventional therapy].
AB  - OBJECTIVES: To evaluate, in long-term open label prospective study, infliximab as
      therapeutic choice for Juvenile Idiopathic Arthritis (JIA) non responsive to
      conventional therapy. METHODS: We enrolled to treat with infliximab 78 JIA
      patients (66 females, 12 males): the mean age was 20.7+/-7.1 years (median 20.9,
      range 5.4-34.9); mean JIA duration was 13.6+/-7.6 years (median 13.5, range 0.4
      31.4). Infliximab, at dose of 3-10 mg/kg/infusion added to weekly subcutaneous
      Methotrexate or other previous DMARDs, was administered by intravenous infusions
      at weeks 0, 2, 6 and every 8 weeks thereafter. Chest X-ray, Mantoux's test,
      electrocardiogram were performed at baseline; laboratory tests and clinical
      evaluation were performed at each infusion. Response was evaluated according to
      ACR improvement criteria. RESULTS: Mean treatment period was 21.6 months+/-18.8
      (median 14.7, range 1.4-72.4). Just after first infusion most of patients
      reported significant improvement in pain, fatigue, morning stiffness. Infliximab
      is still successfully administered to 23 patients (29.5%); 55 (70.5%) patients
      suspended because of: inefficacy (7), infusion reactions (17), adverse events
      (9), disease flare-up after a period of effectiveness on synovitis, pain, and
      morning stiffness (19), remission (2), lack of compliance to treatment (1).
      Infusion reactions, like dyspnea, flushing, chills, headache, hypotension,
      anxiety, throat oedema, were observed in 29 patients (34.5%). Anti-DNA antibodies
      were present in 7 patients (none developed Systemic Lupus Erythematous).
      CONCLUSIONS: Infliximab showed impressive effectiveness treating refractory JIA,
      although most of patients had to discontinue treatment because of disease flare
      up or adverse events. Infliximab may represent a good therapeutic choice in
      patients non-responders to Methotrexate.

PMID- 17435843
TI  - [Correlation between radiologic and ultrasonographic patterns and clinical
      manifestations in symptomatic hip osteoarthritis].
AB  - Increasing amounts of data have recently been published regarding
      ultrasonographic (US) findings of osteoarthritic joints, but very few data
      concern hip joints. In the current study we described US patterns concerning 490
      patients affected by symptomatic hip osteoarthritis (OA) who underwent to intra
      articular injections of hyaluronic products under US guidance. All patients were
      studied by US and X-ray of hip, clinical evaluation was assessed by the
      followings indexes: Lequesne, pain VAS, ICED, Global Physician Assessment and
      Global Patient Assessment. US findings were summarized in four main patterns,
      effusion and synovial proliferation were also detected. The aim of this study was
      to correlate US findings with clinical assessment and radiographic findings
      (according to Kellgren-Lawrence classification). Pearson's r correlation
      coefficient were computed and come out significant and positive between X ray and
      US patterns and between clinical indexes and US patterns. Also the correlation
      between K-L score and US patterns showed a significant positive correlation
      indicating that higher K-L scores are associated with increasing abnormal US
      findings. Our data suggest that ultrasonography of the hip may give useful
      information about the state of synovial membrane, synovial fluid, joint margins
      and bone profile in hip OA. Further studies are needed to evaluate their
      prevalence in hip OA symptomatic and not-symptomatic patients and their
      correlation to treatment outcome.

PMID- 17435844
TI  - [Synoviocyte cultures from synovial fluid].
AB  - The study of the pathogenetic mechanisms of rheumatic diseases is in general
      carried out through "in vitro" systems based on cellular cultures models. The
      difficulties to achieve fresh human tissue prompted us to develop a simpler
      method to obtain fibroblast-like synovial cells from synovial fluid (SF).
      METHODS: SF was collected from the knees of 5 patients with rheumatoid arthritis
      (RA), 4 with osteoarthritis (OA) and 5 with psoriatic arthritis (PsA). The pellet
      obtained after centrifugation was resuspended in DMEM/HamF12 containing 10%
      foetal calf serum, 1% peni-streptomycin, 4 ng/ml of fibroblast grow factor and
      incubated at 37 degrees C in T25 culture flasks. Synoviocytes were also obtained
      from fresh synovial membranes (SM) by explants technique. Both types of cells
      were characterized by immunocytochemistry and their inflammatory response to
      synthetic monosodium urate crystals was studied through the measurement of nitric
      oxide (NO). RESULTS: Adherent synoviocytes were obtained from the culture of 2/5
      SF from RA, 4/4 SF from OA and 5/5 SF from PsA. Synoviocytes isolated from both
      SF and SM expressed surface antigens CD90, CD55, and the intracellular prolyl-4
      hydroxylase. Morphologically, the cells showed the typical spindle-shape
      fibroblast-like appearance. NO levels induced by UMS crystals in SF synoviocytes
      were similar to those obtained in SM synoviocytes. CONCLUSION: Adherent cells
      obtained from SF showed the phenotype and the reactivity of tissue synoviocytes.
      Due to the easy accessibility of SF, this method may represents an useful
      alternative when synovial tissues is not promptly available.

PMID- 17435845
TI  - [The hand: a reflection of arthritis].
AB  - Hand joint involvement in rheumatic diseases is often precocious and predominant
      as compared to other skeleton-muscular regions. Clinical examination not always
      allows for easy detection of fluid outpouring and synovial involvement, and
      undoubtedly does not allow to diagnose pathognomonic bone alterations of several
      rheumatic conditions. Articular ultrasonography is an innocuous methodology,
      easily reproducible and directly applied by a rheumatologist. The aim of this
      vignette is to present ultrasonography elementary lesions of the hand for a
      prompt diagnosis.

PMID- 17435846
TI  - [Gout in Valchiavenna in the XVII century: a case report].
AB  - Gout was a well known disease in antiquity, even if often confused with other
      arthritic conditions. In this paper the XVII century physicians' knowledge about
      gout is discussed. In particular the chapter about gout by Ludovico Settalain his
      book Animadversionum, & cautionum Medicarum (1652) is reported. A story is also
      reported, described in many reports of the time, about a man who died under the
      land-slide which destroyed the town of Piuro in 1618: he was awfully disfigured
      by the land-slide, but was easily recognized by the severe gout he suffered in
      his hands..

PMID- 17435848
TI  - [HIV lipodystrophy syndrome: a new challenge to the endocrinologist].

PMID- 17435849
TI  - [Metabolic changes in HIV infected patient].

PMID- 17435850
TI  - [Do we need to diagnosis Latent Autoimmune Diabetes in Adults (LADA)?].

PMID- 17435851
TI  - [Leptin: aspects on energetic balance, physical exercise and athletic amenorhea].
AB  - The aim of this manuscript was to review the knowledge about leptin, detailing
      its relationship with energetic intake and physical activity. Leptin is an
      adipocyte hormone, recognized mainly for its putative role in control of energy
      expenditure, food intake, body weight and reproductive function. Leptin has still
      important peripheral actions, including its role on the ovarian tissue. The
      intracellular signaling mechanisms are recognized in hypothalamus, but in
      peripheral tissue are not fully understood. The exercise, when practiced by
      women, if not appropriately planned according to food intake, can modify the
      leptin release. When energy imbalances induced by exercise and/or deficient food
      ingestion occurs, low leptin levels are observed, leading to a reduction in GnRH
      (gonadotropin-release hormone), in LH (luteinizing hormone) and FSH (follicle
      stimulating hormone) in pituitary, and consequently a minor release of ovarian
      estrogens. This process is named hypothalamic amenorrhea, and has repercussions
      in the woman's health. In this perspective, it is important to emphasize the need
      to evaluate the energy expenditure from exercise and to formulate adequate
      alimentary plans to these individuals.

PMID- 17435852
TI  - [Leptin, ghrelin, and physical exercise].
AB  - Obesity is a major public health problem in the Western world resulting in
      serious social, physical and psychological damages. The genesis of obesity is
      complex involving a variety of factors such as genetic, psychological, metabolic
      and environmental factors. Progress in endocrinology and metabolism show that
      adipocyte is considered now as an endocrine tissue producing several substance
      including adiponectin, tumor necrosis factor-alpha, interleukin-6 and leptin.
      Specifically, leptin is the main peptide produced by the adipocyte and its serum
      concentration represents an important peripheral signal in the regulation of food
      intake and energy expenditure in mammals. In addition to leptin, a new peptide
      was discovered recently named ghrelin. Ghrelin, a peptide hormone identified in
      the stomach, is directly involved with the regulation of energy balance and
      obesity. Physical exercise has been used as a non-pharmacological tool in
      management of body weight and the effect of physical activity on weight control
      is an important issue for clinical studies in endocrinology field. Thus, this
      review will attempt to update the knowledge of leptin and ghrelin on the body
      weight regulation and the effect of exercise training on these peptide
      concentrations. It can be concluded that the relationship between physical
      exercise and the plasma concentration of these peptides is not clear. The reasons
      for that could be related to the differences in duration, intensity and frequency
      of the training program employed in each study. Indeed, most of the studies have
      not analyzed the intensity of training program by either plasma lactate
      concentration or maximum oxygen consumption. On the other hand, genetic basis
      could also explain the discrepancies found in some studies, since it has been
      shown that polymorphism for a variety of genes might be an important factor to
      determine the differences of cellular response to physical training.

PMID- 17435853
TI  - [Hormonal axes in obesity: cause or effect?].
AB  - Several endocrine changes have been described in the obesity state. The
      corticotropic axis is hyperresponsive and there is enhancement of hormonal
      clearance, but cortisol levels are within the normal range. It is important to
      characterize a pseudo-Cushing in obesity. Leptin seems to be a permissive hormone
      for the beginning of puberty. In adults, gonadotropines are normal, and
      hyperandrogenism and hyperestrogenism are found. In women, insulin resistance has
      a central role in polycystic ovarian syndrome (POS), which is associated to
      ovarian hyperandrogenemia. In obese subjects, growth hormone (GH) is generally
      low and IGF1 is normal. Thyroid function is commonly normal in obese subjects.

PMID- 17435854
TI  - [Corporal fat distribution and lipidic and glicemic profiles of HIV-infected
      patients].
AB  - The aims of this study were to describe anthropometric data and glycemic and
      lipidic profiles of HIV-infected patients treated or not with antiretrovirals
      (ARV) drugs, and to assess association between these drugs and body composition
      changes, lipid and glucose homeostasis disturbances. There were 176 patients
      included (133 ARV-treated patients and 43 ARV-naive). The patients were submitted
      to clinical evaluation, laboratorial analysis, ultrasonographic measurements,
      bioelectrical impedance analysis and skin folds thickness measurements. The ARV
      treated group showed higher waist-to-hip ratio (p= 0.0002), higher intra
      abdominal fat thickness measured by ultrasonography (p= 0.003) and lower
      bicipital (p= 0.01) and tricipital (p= 0.0002) skin folds. This group also showed
      higher triglyceride (p= 0.0002), total cholesterol (p= 0.00007), HDL cholesterol
      (p= 0.009), glucose measurements one hour (p= 0.01) and two hours (p= 0.001)
      after dextrose load, higher levels of fasting insulin (p= 0.03) and higher HOMAR
      index (p= 0.02). The antiretroviral drugs are associated with increased visceral
      fat and decreased peripheral fat pads. Beside that, these drugs are associated
      with atherogenic lipid profile and insulin resistance, two independent risk
      predictors of cardiovascular disease.

PMID- 17435855
TI  - Latent autoimmune diabetes in adults (LADA): usefulness of anti-GAD antibody
      titers and benefit of early insulinization.
AB  - OBJECTIVE: To determine the clinical and laboratory parameters and the
      progression to insulin requirement in two groups of LADA patients separated
      according to GADA titers, and to evaluate the benefit of early insulinization in
      patients at high risk of premature beta-cell failure (high GADA titers). METHODS:
      Among the diabetic adults seen at our service and screened for GADA at diagnosis,
      54 were diagnosed with LADA and classified as having low (> 1 U/ml and < 17.2
      U/ml) or high (> 17.2 U/ml) GADA titers. Fifty-four patients with type 2 diabetes
      (GADA-) were selected for comparison. In addition, 24 patients who had GADA
      titers > 20 U/ml and who were not initially insulinized were compared to 16
      patients who were insulinized at diagnosis. RESULTS: Insulin resistance was
      higher in the GADA- group, followed by patients with low GADA titers. BMI and the
      frequency of arterial hypertension, elevated triglycerides and reduced HDL
      cholesterol were lower in the high GADA+ group, with no difference between the
      GADA- or low GADA+ groups. The high GADA+ group showed a greater reduction and
      lower levels of C-peptide and required insulin earlier during follow-up. Patients
      with GADA titers > 20 U/ml and insulinized early presented no significant
      variation in C-peptide levels, had better glycemic control and required a lower
      insulin dose than patients who were insulinized later. CONCLUSION: We agree that
      patients with LADA should be differentiated on the basis of GADA titers and that
      patients with GADA titers > 20 U/ml benefit from early insulinization.

PMID- 17435856
TI  - [Metabolic profile according to leptin levels in obese patients].
AB  - Increased body mass index and waist circumference are related to cardiovascular
      risk factors. Leptin is an adipocyte-produced hormone and regulates body weight.
      Leptin is directly related to body fat. To evaluate the relationship between
      leptin and metabolic profile in obese subjects, we studied 119 patients.
      Anthropometric, laboratory, body composition (by bioelectrical impedance) and co
      morbidity data were collected. The analysis was performed in the female
      population (86.6%): average age: 42 +/- 13 years; hypertension, type 2 diabetes
      and grade III obesity were present in 61.9%, 20.2% and 58.3%, respectively.
      Leptin levels were positively related to insulin resistance (IR). HOMA-IR was
      related to metabolic abnormalities of IR. No differences were demonstrated
      between lipid profile, glycemia, body composition and tertiles of leptin
      corrected by fat weight. A significant difference in HOMA-IR was present when the
      2nd and 3rd tertiles of leptin corrected by fat weight [3.4 (2.8-4.1) vs. 5.3
      (4.1-6.5), p=0.011] were compared. In conclusion, leptin corrected by fat weight
      did not influence lipid profile and glycemia in moderate to severe obese women
      with similar percent body fat. Leptin should not be considered an independent
      factor affecting lipid metabolism.

PMID- 17435857
TI  - [Fat intake and hypercholesterolemia in a probabilistic sample of adolescents
      from Niteroi, Rio de Janeiro].
AB  - OBJECTIVE: To evaluate the relationship between fat intake and serum cholesterol.
      METHODS: A survey was conducted in a probabilistic sample of students from public
      schools in Niteroi, state of Rio de Janeiro, Brazil. Anthropometric data were
      collected on 610 youngsters, 573 of them had blood drown, and 539 answered a
      simplified questionnaire on fat intake. Multivariate linear regression included
      as confounders: parents' cholesterolemia, adolescent age and body mass index
      (BMI). RESULTS: The prevalence of high concentrations (> 170 mg/dL) of serum
      cholesterol was 31.2%. Both sexes presented high frequencies (45% approximately)
      of inadequate intake of fatty foods. Prevalence of overweight was 15.7%, without
      significant statistical difference between sexes (p= 0.83). Total fat intake as
      measured by the questionnaire and each one of the nine high fat items was not
      associated with youngsters' cholesterol. Among girls BMI and parents'
      hypercholesterolemia were associated with cholesterol levels, but for boys only
      age showed statistically significant association. Lack of association between fat
      intake and cholesterol levels was observed. CONCLUSION: The combined higher
      prevalence of hypercholesterolemia, overweight and intake of high fat foods
      suggest that only public health action may curb these epidemics. This may
      indicate that overall energy intake should be the target of the actions.

PMID- 17435858
TI  - [Impact of the habitual physical activity on lipid profile in adults].
AB  - The present study was designed to analyze the impact of the habitual physical
      activity determined by International Physical Activity Questionnaire (IPAQ) on
      lipid profile in representative sample of adults. A sample of 361 subjects (196
      women and 165 men) aged 20-60 years old was included in the study. Plasma lipid
      concentrations were measured by standard procedures. The results showed that HDL
      cholesterol and VLDL-cholesterol levels were not significantly different across
      physical activity groups in both sexes. Total cholesterol, LDL-cholesterol and
      triglycerides were significantly different across physical activity groups in
      women and men, but the pattern of variation was different between genders. The
      results from logistic regression analysis indicated that the odds ratios for low
      plasma lipid levels was significant only in subjects classified as very active
      compared with sedentary. In conclusion, the results suggest that increased
      habitual physical activity determined by IPAQ present significant impact in the
      plasma lipid profile in adults of both sexes, independently of the age and of the
      variations of the body weight.

PMID- 17435859
TI  - [Can bariatric surgery cure metabolic syndrome?].
AB  - OBJECTIVES: To evaluate the impact of bariatric surgery on the metabolic syndrome
      (MS) and what are the criteria that contribute the most for its exclusion after
      surgery. The progress of leucometry was also analyzed. METHODS AND PROCEDURES: 47
      obese women with MS were evaluated. All patients were operated with the Roux-en-Y
      vertical gastric bypass technique, with the insertion of a contention ring on the
      gastro-jejune anastomosis (Fobi-Capella). Patients were evaluated before and on
      the first year post-surgery. RESULTS: Fasting glucose presented a relevant
      decrease at 3 months after surgery. After 12 months, all 20 patients who had DM2
      or altered fasting glucose presented normal levels of fasting glucose and
      glicated hemoglobin, and none of them was using any anti-diabetic drug.
      Triglycerides levels were reduced by 49.2%, whereas HDL-cholesterol increased by
      27.2%. Systolic and diastolic blood pressures were reduced by an average of 28.7
      and 20.8 mmHg, respectively. Leucocytes counting fell from 7671/microL to
      6156/microL. Fasting glucose, triglycerides, DBP, SBP and HDL-cholesterol were
      the variables that contributed most for the reduction of MS. At the end of the
      first year, elimination of MS occurred in 80.9% of the patients. DISCUSSION:
      Bariatric surgery reduces resistance to insulin and consequently the
      cardiovascular risk factors.

PMID- 17435860
TI  - [Prevalence of macroprolactinemia among 115 patients with hyperprolactinemia].
AB  - Macroprolactinemia is characterized by the predominance in the serum of
      macroprolactin, a prolactin (PRL) with high molecular mass and low biological
      activity that does not need treatment. The prevalence of macroprolactinemia was
      evaluated in 115 consecutive patients with hyperprolactinemia. Among them, 19
      (16.5%) had solely macroprolactinemia, 4 (3.5%) polycystic ovary syndrome, 7
      (6.1%) acromegaly, 8 (6.9%) idiopathic hyperprolactinemia, 10 (8.6%) primary
      hypothyroidism, 14 (12.2%) clinically non-functioning pituitary adenomas, 20
      (17.4%) drug-induced hyperprolactinemia and 33 (28.7%) prolactinomas. The
      diagnosis of macroprolactinemia was established by the demonstration of a PRL
      recovery < 30% after treatment of sera with polyethylene glycol. Among the 19
      patients with isolated macroprolactinemia, 16 (84.2%) were female and 12 (63.2%)
      were asymptomatic, while 4 (21%) presented with oligomenorrhea and 3 (15.8%) with
      galactorrhea. In contrast, only 11.5% of individuals with other causes of
      hyperprolactinemia were asymptomatic (p< 0.001). Prolactin levels in cases of
      macroprolactin ranged from 45.1 to 404 ng/mL (mean 113.3 +/- 94.5) but in 15
      (78.9%) were < 100 ng/mL. Our findings demonstrate that macroprolactinemia is a
      common condition and, therefore, we suggest that it should be routinely screened
      in patients with hyperprolactinemia.

PMID- 17435861
TI  - [Prader-Willi syndrome: metabolic aspects related to growth hormone treatment].
AB  - AIM: The focus of this study was to evaluate the metabolic profile of Prader
      Willi Syndrome (PWS) patients treated with growth hormone. PATIENTS AND METHODS:
      Seven patients (four boys and three girls) with ages between six years and six
      months and 14 years and 11 months were treated with GH 0.1 U/kg/day subcutaneous
      by six times a week, for two years. Anthropometric data, lipids, glucose, IGF-I
      and body composition were evaluated at baseline and after 12 and 24 months.
      RESULTS: IGF-I levels increased in all cases. Skin folds decreased. The mean
      reduction in body fat was 5.0% and the mean increased in lean mass was 7.6 kg in
      the prepubertal patients. The pubescent girl increased 4.8 kg and showed a 5.6%
      decrease in fat mass. A mean gain in the bone mass was 0.07 g/cm(2) (7.3%) in
      prepubescent cases, and 0.02 g/cm(2) (2.0%) in the pubescent girl. CONCLUSION: In
      our study GH treatment improved lean body and bone masses and had beneficial
      effect on lipid values.

PMID- 17435862
TI  - Management of low-risk patients with thyroid carcinoma and detectable
      thyroglobulin on T4 after thyroidectomy and ablation with iodine-131.
AB  - OBJECTIVE: To evaluate the positive predictive value of detectable Tg during T4
      therapy (Tg on T4) in patients with thyroid cancer after total thyroidectomy and
      remnant ablation, discussing the work-up in this situation and the empirical
      indication of 131I. PATIENTS AND METHODS: Initially, 234 low-risk patients [tumor
      < 5cm, completely resected, no extensive extrathyroid invasion (pT4)] submitted
      to total thyroidectomy and ablation with 131I (3.7-5.5 GBq) who presented no
      ectopic uptake on RxWBS were studied. Of these, 23 patients with detectable Tg on
      T4 (> 1ng/ml) during the first year after initial therapy were selected. RESULTS:
      Metastases were detected by neck US in 7 patients, by chest CT in 2 and by US and
      CT in 3. Four of five patients with lung metastases upon CT had a positive RxWBS.
      Eleven patients with negative US and CT received a new 131I dose (without DxWBS),
      and RxWBS showed ectopic uptake in 3 patients. Among the patients with negative
      RxWBS, 7 remained free of apparent disease and Tg was declining (5 with
      undetectable Tg on T4 at the end of the study). One patient presented an increase
      in Tg and FDG-PET was positive for lymph node and bone metastases. CONCLUSIONS:
      All patients with Tg on T4 > 5ng/ml presented apparent disease. In these cases,
      even when US and CT are negative, the administration of a therapeutic dose of
      131I (without DxWBS) and FDG-PET are recommended. Among patients with detectable
      Tg on T4 <or= 5ng/ml and negative US and CT, only 12% presented ectopic uptake on
      RxWBS. These cases could be followed up by monitoring Tg on T4, and RxWBS and FDG
      PET should only be performed if this marker does not decrease after 1-2 years.

PMID- 17435863
TI  - [Prevalence of the use of anabolic agents among strength training apprentices in
      Porto Alegre, RS].
AB  - This study aimed to determine through a questionnaire applied to interviewers,
      the current or past use of anabolic androgenic steroids (AAS), as well as other
      hormones (OH), and other medicines (OM), food supplement and illicit drugs among
      strength training apprentices in the city of Porto Alegre, RS. We interviewed 288
      subjects draw from a sample of 13 gyms. The prevalence of current and past use of
      AAS was about 11.1% (32/288), OH 5.2% (16/288) and OM 4.2% (12/288). The most
      used AAS were nandrolone and stanozolol; the OH were gonadotropin,
      triiodothyronine (T3) and OM, like lipostabil, diuretics and veterinary medicines
      (Monovin E). The most frequent side-effects were behavioral such as humor
      oscillation, irritability and hostility, and endocrine disturbances such as acne
      and increased or decreased libido. When analyzed together with other hormones in
      a variable named "hormonal agents" (AH), AAS presented a statistical difference
      (p< 0.05) among genders considering that the most frequent use of AH occurred
      among men and those who consume food supplements. The comparison of these
      findings to other national and international results is difficult due to the
      epidemiological design. Even if it is considered, the observed prevalence
      suggests that preventive attitudes as well as special care in the orientation and
      education of this population must be taken.

PMID- 17435864
TI  - [Increase in prevalence of diabetes mellitus as a cause of dialytic end-stage
      renal disease: analysis of 20 years in the west region of Parana].
AB  - Diabetic nephropathy (DN) is the main cause of chronic kidney disease (CKD) in
      developed countries. OBJECTIVE: To observe if there was an increase in the
      prevalence of diabetes mellitus (DM) of CKD in the last 20 years and to analyze
      comparatively the survival on dialysis of diabetic and non-diabetic patients.
      METHODS: Retrospective analysis of patients kept on dialysis in the west region
      of Parana State in the period between 1985-2005. Survival analysis was performed
      using Kaplan-Meier Curves. RESULTS: In the period, 645 patients were admitted to
      dialysis. In 16.1% DM was the cause of the CKD. It was observed a progressive
      increase in the prevalence of DM as a cause of CKD. Patient survival was lower in
      diabetics. CONCLUSIONS: The prevalence of DM as a cause of CKD increased in the
      last 20 years in our region. The survival rates were lower in diabetic than in
      non-diabetic patients.

PMID- 17435865
TI  - [Nelson's Syndrome: a case report].
AB  - The aim of this article is to present and discuss several aspects of the
      pathogenesis, the clinical, hormonal, and imaging diagnosis, and the treatment of
      Nelson's syndrome, based on a typical patient's report, in whom several
      therapeutic approaches were shown to be ineffective.

PMID- 17435866
TI  - [Endogenous persistent hypoglicemia of adult: case report].
AB  - Persistent Hyperinsulinemic Endogenous hypoglycemia in adults is, in most cases,
      due to Insulinoma. Nesidioblastosis, a peculiar functional hyperinsulinemia from
      hypertrophic beta cells, has been described mainly in newborns. This article
      describes a 34-year-old patient who presented hyperinsulinemic endogenous
      hypoglycemia clinical and laboratorial situation (Fasting glycemia: 54 mg/dl /
      Reference Interval (RI): 60-99 mg/dl; Serum insulin: 70.9 mcU/ml / RI: < 29.1
      mcU/ml; e C peptide: 7.1 ng/ml / RI: 1.1-5.0 ng/ml). It was suspected Insulinoma.
      Because of the lack of typical images in radiologic exams (ultrasonography and
      computerized tomography) it had been decided to do laparotomy, but it was not
      found any macroscopic pancreatic tumor. Histological and histochemistry
      examination of a distal pancreatic segment showed alteration suitable to
      nesidioblastosis. The patient presented clinical stability during the next two
      months, however, after that, there was a recurrence of a hypoglycemia crisis,
      refractory to Octreotide administration. It was done "octreoscan", which showed
      expanded nesidioblastosis, being done extensive partial pancreatectomy.
      Octreotide was used again, with a good control of the hypoglycemia crisis. As it
      is an uncommon diagnosis in an adult, the objective of this article is to
      describe the diagnostic and therapeutic aspects in cases of hyperinsulinemic
      endogenous hypoglicemia.

PMID- 17435867
TI  - [Case report: diabetes flatbush - from ketoacidosis to non pharmacological
      treatment].
AB  - A subgroup of patients presents diabetic ketoacidosis at the onset of diabetes
      mellitus (DM) but later is classified as type 2 DM based on the clinical follow
      up. These individuals, most commonly obese of African or Hispanic origin, have
      negative auto-antibodies associated with type 1 DM, but frequently HLA class II
      DRB1*03 and/or DRB1*04 are detected. This peculiar subtype of DM is commonly
      referred to as diabetes flatbush. Here we report the case of a Caucasian patient
      that exhibited the described evolution and in whom it was possible to withdraw
      insulin therapy. The possible factors associated with this favorable development
      are also discussed.

PMID- 17435868
TI  - [Antineutrophil cytoplasmic antibody (Anca)-associated autoimmune disease induced
      by propylthiouracil].
AB  - Antithyroid drugs sometimes cause severe complications. Propylthiouracil (PTU)
      can be associated to ANCA positive vasculitis, most often related to
      myeloperoxidase subtype (ANCA-MPO). Our objective is to describe a female patient
      with Graves' disease, who developed PTU induced-autoimmune disease, with
      cutaneous, pulmonary, and renal lesions, associated with ANCA. Histopathological
      examination revealed diffuse pulmonary hemorrhage, and focal segmental
      glomerulosclerosis at the kidney biopsy. She was treated with systemic
      corticosteroid therapy and cyclophosphamide, with clinical improvement. This case
      highlights the need for greater awareness of this relatively rare adverse effect
      of propylthiouracil.

PMID- 17435869
TI  - [Early infancy onset of type 1A diabetes mellitus in dizygotic twins: association
      with genetic and environmental factors].
AB  - The onset of type 1A diabetes before the first year of age is a rare condition
      and is probably due to an interaction between genetic and environmental factors
      (infection), which, together, may explain such an early event. Studies say that
      about 15% of newly diagnosed type 1 diabetic patients had human Cytomegalovirus
      (CMV) specific viral genome in their lymphocytes. We report two cases of
      dizygotic twins with type 1 diabetes onset in their first 9 months of age, with
      genetic homogeneity (for HLA DR3/DR4 alleles), a history of CMV infection
      (positive IgG and urinary PCR) and positive antibody anti-GAD (9.6 UI/ml),
      present only in the second twin. Although they were dizygotic twins, which
      concordance rate is 3.8%, they assume the equivalent risk as monozygotic (40%) as
      they have similar high risk genotype (HLA) for type 1 diabetes. We believe that
      both time concordance and also the early onset of diabetes are due to an
      association between infection and the high genetic liability.

PMID- 17435870
TI  - [Prevalence of metabolic syndrome in patients of south of Brazil with polycystic
      ovary syndrome (PCOS)].

PMID- 17435871
TI  - Access to health inputs: challenges for the Third World.

PMID- 17435872
TI  - [Anxiety during pregnancy, prematurity, and low birth weight: a systematic
      literature review].
AB  - The purpose of this systematic literature review was to examine publications that
      had investigated the effect of anxiety on prematurity and/or low birth weight.
      The PubMed, BVS, CINAHL, and HEALTHSTAR databases, published from 1966 to 2006,
      were tracked using the following key words: "anxiety", "pregnancy", "low birth
      weight", and "prematurity". Thirteen studies were found: 11 cohorts, 1 cross
      sectional, and 1 case-control. Most studies (7/13) were conducted in the United
      States. The most reliable results came from four studies, whose strengths were:
      exclusion of adolescents and/or women older than 34 years, studies that analyzed
      anxiety during the second and/or third trimester of pregnancy, used validated
      scales to measure anxiety, kept loss-to-follow-up rates below 30%, and applied
      adequate control of confounders. Anxiety during pregnancy was associated with
      prematurity and/or low birth weight in eight studies. Odds ratios and relative
      risks varied from 1.08 to 2.31. Carefully designed and well-conducted studies are
      still needed to clarify the relationship between anxiety during pregnancy,
      prematurity, and low birth weight considering that the accumulated evidence
      remains controversial.

PMID- 17435873
TI  - [The Workers' Health field: reclaiming knowledge and practices in the interface
      between work and health].
AB  - This article discusses the underlying theoretical and operational premises in the
      fields of workers' health and occupational health, highlighting their respective
      frameworks and epistemological differences, based on Foucaultian archeology. The
      theme is particularly relevant, due to: the apparently limited attention to
      interdisciplinary research approaches in workers' health; various setbacks in
      public health measures at the social policy level; related weaknesses in the
      Brazilian trade union movement; and the conceptual misinterpretations drafted
      into the final report of the 3rd National Workers' Health Conference in November,
      2005, convened by the Ministries of Social Security, Health, and Labor. The event
      resulted from the Workers' Health Conferences held in various States and
      Municipalities, mobilizing some 100,000 activists throughout Brazil and electing
      the delegates to the 3rd National Conference.

PMID- 17435874
TI  - Infant mortality in the Federal District, Brazil: time trend and socioeconomic
      inequalities.
AB  - This study examined the trend in the infant mortality rate in the Federal
      District of Brazil (or Greater Metropolitan Brasilia, the national capital) from
      1990 to 2000, analyzing the rate according to 5 administrative areas stratified
      by mean family income, from 1996 to 2000. An ecological time-series study was
      conducted using the Information Systems on Live Births and Mortality, produced by
      the Brazilian Ministry of Health. The infant mortality rate (IMR) decreased by
      45.2% from 1990 to 2000, from 26.3 per 1000 live births to 14.4, or a mean annual
      reduction of 5.34% (R(2) = 0.9397; p < 0.0001). During this period there was a
      higher proportion of neonatal deaths. However, a higher percentage change
      occurred in the post-neonatal period (-59.0%, R(2) = 0.8452, p < 0.0001).
      Investigation of the IMR in the various areas of the Federal District showed a
      reduction in differences among the regions with respect to the component rates;
      however, substantial disparities persisted in relation to the income variable.
      The results suggest the need for effective interventions in the determinants of
      neonatal and post-neonatal mortality in order to improve maternal and infant
      health in all socioeconomic groups in the Federal District.

PMID- 17435875
TI  - [Tobacco, alcohol, and drug use by teenagers in Pelotas, Rio Grande do Sul State,
      Brazil: a gender approach].
AB  - This study assesses the relationship between gender and use of psychoactive
      substances (alcohol, nicotine, and illicit drugs) by teenagers. In 2002, a cross
      sectional study was carried out in the urban area of Pelotas, southern Brazil.
      Multi-stage sampling was used to obtain a sample of adolescents, 15 to 18 years
      of age. Subjects were interviewed using a self-applied confidential
      questionnaire. Smoking was more prevalent among girls, while alcohol consumption
      in the previous month was more common among boys. Meanwhile, the proportion of
      adolescents that reported drug use in the previous month was unrelated to gender.
      Higher cigarette consumption by girls suggests an increase in smoking by women in
      the future, which highlights the need for a special focus on this area.

PMID- 17435876
TI  - [Food security in Terena indigenous families, Mato Grosso do Sul, Brazil].
AB  - This study aims to describe the food security situation among Terena families in
      the villages of Agua Azul, Olho D'Agua, and Oliveiras in Mato Grosso do Sul
      State, Brazil. The Brazilian Food Insecurity Scale was adapted to 15 questions
      that reflect food insecurity at different levels of intensity. A survey was
      conducted in the villages with 49 families that had under-five children.
      Information was obtained on income, family size, maternal education, and
      children's food intake. 75.5% of families showed some level of food insecurity
      (22.4% low, 32.7% moderate, and 20.4% high). A large percentage (67.3%) of the
      families live with fear of lack of food. One-fourth of women had experienced
      hunger during the month prior to the survey, and 14.3% (7) reported the same
      condition for children in the household. More serious food insecurity was
      observed in families with lower per capita income and lower maternal education,
      more family members, and more children per family group in which the children's
      diet was insufficient, especially in protein and iron.

PMID- 17435877
TI  - [Changes in the epidemiological pattern of malaria in a rural area of the middle
      Rio Negro, Brazilian Amazon: a retrospective analysis].
AB  - A retrospective study on reported malaria cases in the municipality (county) of
      Barcelos, Amazonas State, Brazil, was performed from 1992 to 2004, emphasizing
      the high endemic area along the Padauiri, an affluent of the Rio Negro. 16,795
      cases were reported, 10,318 (61.4%) from the rural area and 6,477 (38.6%) from
      the urban area. Mean annual parasite index for the period was 136.7 per 1,000
      inhabitants in the urban area and 613.6 per 1,000 in the rural area of Barcelos
      and 708.9 per 1,000 in the Padauiri area. In the latter area, two periods were
      considered: one epidemic, from 1992 to 1998, and the other post-epidemic, from
      1999 to 2004. Comparing the two periods, the male/female ratio changed from 1.8
      to 1.14, mean patient age from 17.9 to 14.8, proportion of Plasmodium falciparum
      cases from 51.9% to 23.7%, proportion of slides with low P. falciparum parasite
      density from 35.3% to 44.9%, and proportion of P. vivax from 24% to 35% (all
      these differences were statistically significant, with p < 0.05). The changes in
      the epidemiological pattern of malaria in the Padauiri area will be further
      elucidated through prospective studies.

PMID- 17435878
TI  - [Time to kidney transplantation in chronic renal failure patients in the State of
      Rio de Janeiro, Brazil, 1998-2002].
AB  - This study analyzes the characteristics of 14,419 chronic renal failure patients
      treated with hemodialysis and time to first kidney transplantation in the State
      of Rio de Janeiro, Brazil, from 1998 to 2002. Survival analysis methods were
      used, such as the Kaplan-Meier non-parametric method and the semi-parametric
      method with the Cox proportional hazards model. Besides the survival model for
      transplantation, time to death was analyzed to compare the two models' estimates.
      During the period studied, only 6.3% of patients received transplants, 32.4% were
      referred for transplantation, and 6.3% were included on the waiting list. Odds of
      transplantation were greater for those who had been referred, those on the
      waiting list, and younger patients. Diabetes mellitus reduced the probability of
      conducting transplantation by 35%. All the estimates showed directions opposite
      to those obtained for the mortality survival model.

PMID- 17435879
TI  - No difference in leprosy treatment outcomes comparing 12- and 24-dose multidrug
      regimens: a preliminary study.
AB  - A comparative study was performed on the initial and final bacillary indexes of
      213 multibacillary leprosy patients who received 12 doses (Group 1: 128 patients)
      or 24 doses (Group 2: 85 patients) of multidrug therapy (MDT/WHO) to measure the
      effectiveness of the two regimens. All patients were evaluated at treatment
      baseline, 12 months, and 24 months. The reduction in bacillary levels and mean
      bacillary indexes at 24 months was similar in the two groups. No statistical
      difference in reaction rates was observed between the two treatment regimens.

PMID- 17435880
TI  - [Behaviors related to sunlight exposure versus protection in a random population
      sample from 15 Brazilian State capitals and the Federal District, 2002-2003].
AB  - This article examines region-specific relations between prevalence of protection
      against sunlight and socio-demographic and behavioral variables in Brazil. Data
      were derived from a cross-sectional population-based random sample. Information
      on sunlight exposure was available for a total of 16,999 individuals 15 years and
      older. Comparing the North and South of Brazil, crude differences between women
      and men in the use of "sunscreen" and "protective headwear" were +10.9% (95%CI:
      7.1; 14.6) and -11.6% (95%CI: -17.0; -6.3) in the North and +21.3% (95%CI: 17.7;
      24.9) and -16.0% (95%CI: -20.2; -12.5) in the South. Adjusted differences by
      selected variables confirmed that women use more sunscreen protection and less
      headwear protection as compared to men in both the North and South, but the
      difference was not homogeneous by region (interaction term p value < 0.05).

PMID- 17435881
TI  - [The Hospital Pharmacy Survey in Brazil: a proposal for hierarchical organization
      of hospital pharmaceutical services].
AB  - This paper discusses the development of a methodological approach to classify
      hospital pharmacies according to their performance, measured by structure and
      process indicators. The method considers the influence exerted on performance by
      the level of care in the hospital and the interdependence among pharmaceutical
      activities. Algorithms for assessing performance of hospital pharmacies were
      constructed for each level of care. Different weights were used for core
      activities in the pharmacy and other specific activities, according to the level
      of care in the hospital where the respective service was provided. This
      methodology allowed classifying hospital pharmacies from best to worst, based on
      performance. Independently of level of care in the hospital, no hospital
      pharmacies were classified as high-performance, and more than 50% were classified
      as low-performance.

PMID- 17435882
TI  - [Hospital case fatality associated with coronary angioplasty in Rio de Janeiro
      State, Brazil, 1999-2003].
AB  - This study analyzes hospital case fatality associated with percutaneous
      transluminal coronary angioplasties (PTCA) covered by the Brazilian Unified
      National Health System (SUS) and performed in hospitals in the State of Rio de
      Janeiro from 1999 to 2003. PTCA data were obtained from the State Health
      Department's database on Authorizations for Hospital Admissions. Case fatality
      rates were estimated according to age, gender, diagnosis, and hospital. Overall
      case fatality was 1.9% in 8,735 PTCAs. The lowest rate was associated with angina
      (0.8%) and the highest rates with acute myocardial infarction (6%) and other
      diagnoses (7%). In the 50-69-year bracket, case fatality was higher in women. In
      the over-70 group, it was almost three times that of the youngest group (4%
      versus 1.4%). There was great variability among PTCA case fatality rates in
      different hospitals (from 0 to 6.5%). Ongoing monitoring of PTCAs is thus
      necessary in clinical practice. In conclusion, PTCA performance was still
      unsatisfactory under the Unified National Health System.

PMID- 17435883
TI  - [The Health Information System for Indigenous Peoples in Brazil (SIASI): design,
      structure, and functioning].
AB  - The Brazilian Health Information System for Indigenous Peoples (SIASI) was
      created in 1999 as part of the Sub-System for Indigenous Peoples' Health Care.
      The aim was to improve availability and access to crucial health information for
      planning, implementation, and evaluation. The current study analyzes the SIASI,
      focusing on its creation, implementation, functioning, potential, and
      limitations. Documents were surveyed in the Indigenous Peoples' Health Department
      of the National Health Foundation, followed by comparative analyses with other
      health information systems. The SIASI is organized in eight modules, three of
      which were in operation at the time of the study. The system's main limitations
      involve data collection instruments, human resources training, lack of interface
      with other national health information systems, difficult access to the data, and
      non-utilization of the data to plan subsequent health activities. The
      potentialities include the system's simplicity, comprehensiveness, and
      possibilities for disaggregating data. The study highlights the importance of a
      specific health information system for indigenous peoples, due to their socio
      cultural and demographic specificities.

PMID- 17435884
TI  - [Risk factors for asthma in adults in Pelotas, Rio Grande do Sul State, Brazil].
AB  - Asthma incidence and mortality rates have increased in recent years. The present
      cross-sectional survey aimed to measure asthma prevalence and risk factors in a
      random sample of 1,968 individuals (20-69 years of age) in Pelotas, Rio Grande do
      Sul State, Brazil. Overall prevalence of "current asthma symptoms" was 6%,
      varying according to diagnostic criteria. Associated risk factors in the crude
      analyses were: female gender, age 60-69 years, non-white skin color, low
      education, low family income, family history of atopy and asthma, personal
      history of atopic disease, smoking, low body mass index, and minor psychiatric
      disorders. In the multivariate analysis the following risk factors remained
      associated with "current asthma symptoms": mother and father with asthma history,
      minor psychiatric disorders, age 60-69 years, household income less than 1.01
      minimum wage, history of atopic disease, and female gender. The results highlight
      the variation in asthma prevalence according to diagnostic criteria and confirm
      the importance of genetic, social, and lifestyle factors.

PMID- 17435885
TI  - GIS applications for mapping and spatial modeling of urban-use water quality: a
      case study in District of Cuiaba, Mato Grosso, Brazil.
AB  - A cross-sectional study utilizing spatial analysis techniques was conducted to
      study water quality problems and risk of waterborne enteric diseases in a lower
      middle-class urban district of Cuiaba, the capital of Mato Grosso State, Brazil.
      Field surveys indicate high rates of supply water contamination in domiciles and,
      conspicuously, in public and private schools. Logistic regression models
      developed for the variables turbidity, Escherichia coli, total coliforms, and
      intestinal parasite infection did not identify singular explanatory factors for
      the supply water conditions and elevated incidences of enteric diseases among
      children. The contamination problems were found to be the result of precarious
      conditions involving both public infrastructure and in-building sanitary
      installations and their maintenance. GIS methods were successfully applied to
      create spatial datasets for logistic regression model building and to construct
      risk maps using regression coefficients.

PMID- 17435886
TI  - [Bacteriological diagnosis of tuberculosis in Argentina: results of a national
      survey].
AB  - In order to assess laboratory resources, practices, and biosafety measures during
      mycobacterial testing and determine the usefulness and scope of mycobacterial
      techniques, a cross-sectional survey of public laboratories was conducted in
      Argentina using a structured questionnaire. Sputum smear analysis showed that
      both smear and culture testing centers are being provided at or above the WHO
      recommended density for such facilities. The microscopy quality assessment
      program covered most high-demand laboratories. Mean number of sputum smears per
      patient was low (1.6). The use of inadequate personal respiratory protection was
      identified in 25% of culture laboratories. Jurisdictions that cultured a higher
      proportion of their smear-tested sputa identified a higher proportion of smear
      negative cases. The percentage of smear negatives among all bacteriologically
      confirmed pulmonary cases was 18.9%, while most extrapulmonary cases were
      confirmed by culture (71.3%). In conclusion, increasing the number of sputa
      studied by microscopy and culture (while expanding the coverage of the quality
      assessment program) is a priority; adequate respiratory protection and regular
      medical evaluation of laboratory staff is still needed in some laboratories.

PMID- 17435887
TI  - [Obesity and risk factors for the development of chronic non-transmissible
      diseases among consumers in a foodservice unit].
AB  - This study aimed to assess nutritional status and risk factors for chronic non
      transmissible diseases in 1,252 factory employees in Santa Catarina State,
      Brazil. The following variables were studied: nutritional status, waist
      circumference, blood pressure, blood glucose levels, age, and schooling.
      Overweight and obesity were observed in 45% and 10% of the sample, respectively,
      with a significant association between nutritional status and gender, but not
      between nutritional status and schooling, adjusted for age. The proportion of
      high waist circumference was 33%, with a significant difference between genders.
      High systolic blood pressure (SBP) and diastolic blood pressure (DBP) were
      present in 18% and 11% of the employees, respectively, with a significant
      association between genders after adjusting for age. Type II diabetes mellitus
      was diagnosed in 2% of the sample and altered glucose levels in 4%. After
      adjusting for age, the only variables significantly associated with waist
      circumference were SBP and DPB. The results allowed the implementation of
      preventive and educational activities to improve employees' quality of life and
      productivity.

PMID- 17435888
TI  - [Pap smear screening for the control of cervical cancer in Minas Gerais State,
      Brazil, 2002].
AB  - This article analyzes the implementation of Pap smears by the Cervical Cancer
      Control Program in 2002 in women 25-59 years of age residing in 850
      municipalities (counties) in Minas Gerais State, Brazil. Cluster analysis was
      performed to classify municipalities by: number of Pap smears performed; test
      findings; and adequacy of slides. The variable "satisfactory slide, but limited
      by" was the principal factor for classifying municipalities into 5 clusters.
      Spatial representation of clusters indicated a more critical situation in the
      North, Jequitinhonha, Vale do Mucuri, and Vale do Rio Doce "meso-regions" of
      Minas Gerais and identified operational problems resulting from inadequate
      collection of material, with more "desiccated" slides observed in the North of
      the State and more slides with "absent endocervical cells" in the Center and
      South. The methodology allowed identifying clusters of municipalities with
      problems in the screening process, related to quality of sampling and fixing and
      reading of slides.

PMID- 17435889
TI  - [Asthma in 13-14-year-old schoolchildren in the city of Nova Iguacu, Rio de
      Janeiro State, Brazil: prevalence, severity, and gender differences].
AB  - This study aimed to assess the prevalence and severity of asthma and related
      symptoms and the associations with gender in 13-14-year-old schoolchildren in the
      city of Nova Iguacu, Rio de Janeiro State, Brazil. The cross-sectional study used
      the self-applied International Study of Asthma and Allergies in Childhood (ISAAC)
      questionnaire. The sample included 3,033 students randomly selected from 37
      public and private schools. Prevalence of "any history of wheezing" was 26%, as
      compared to 11.7% within the last 12 months ("current asthma"), and was higher
      among girls (PR = 1.46; 95%CI: 1.31-1.62 and PR = 1.72; 95%CI: 1.35-2.21).
      Symptoms associated with severity, like "sleep disorders" and "speech limited by
      wheezing" were associated with female gender (PR = 2.57; 95%CI: 1.77-3.73 and PR
      = 2.07; 95%CI: 1.25-3.43). Although asthma prevalence was lower than in other
      Brazilian cities, it was still high among schoolchildren in Nova Iguacu, and was
      more frequent and severe among girls. Further research is needed to explain the
      observed differences.

PMID- 17435890
TI  - [Drug prescription and dispensing from the patient's perspective: a community
      based study in Fortaleza, Ceara State, Brazil].
AB  - The objective of this study was to analyze aspects of the physician-patient and
      pharmacist-patient relationship, based on patients' opinions. It consists of
      community-based research performed in Fortaleza, Ceara State, Brazil, where 957
      persons were interviewed; 904 answered questions about the last visit to the
      physician and 831 about the last visit to the pharmacy. The data reflect several
      aspects of medical and pharmaceutical practice and patients' attitudes towards
      the questions posed and information provided to guide rational use of drugs. In
      the therapeutic choice, physicians failed to ask their patients about
      hypersensitivity to drugs (65%) and use of other medication (64.1%) and ignored
      recommendations concerning adverse drug reactions (73.3%) and drug interactions
      (58.2%). The situation was even worse in hospitals, where in most cases a
      pharmacist's assistant was responsible for dispensing to patients (57.1%). The
      study suggests poor quality in the medical and pharmaceutical roles and patient
      apathy towards proceedings involving the prescription and receipt of drugs in
      pharmacies, as well as in rational use.

PMID- 17435891
TI  - [Metals in landfill leachate in Ribeirao Preto, Sao Paulo State, Brazil, and its
      relevance for public health].
AB  - This study analyzed the levels of cadmium, lead, copper, chromium, manganese,
      mercury, and zinc in leachate from the Ribeirao Preto landfill site in Sao Paulo
      State, Brazil. Samples were taken from runoff tanks in Module I (operating from
      1989 to 2000) and Module II (operating since November 2000). Metal levels were
      measured by atomic absorption spectrophotometry at the University of Sao Paulo in
      Ribeirao Preto (University Hospital). Results were compared to the maximum limits
      for metal concentration in liquid effluents set by Ruling 357/2005 of the
      National Environmental Council (CONAMA). The study also investigated whether
      there was any attenuation in metal concentrations in the leachate, considering
      differences in the life spans of the various Ribeirao Preto landfill site
      modules. Metal levels in the samples were within the maximum limits for cadmium,
      chromium, copper, mercury, and manganese, but lead and zinc were above the limits
      set by the above-mentioned ruling.

PMID- 17435892
TI  - [HIV prevention using the operative group approach among men who have sex with
      men in Sao Paulo, Brazil].
AB  - This study aimed to evaluate the operative group as a preventive approach among
      men who have sex with men that use two public health services in the city of Sao
      Paulo, Brazil. One hundred volunteers were randomly allocated to two groups
      (intervention and control, with 50 each). All participants answered
      questionnaires in two phases: before the intervention and six months after its
      conclusion. Effect was measured by comparing the groups for the following
      outcomes: median number of anal sex acts without condoms and responses from the
      participants to questions about HIV infection. 69 participants completed the
      study (34 in the prevention group and 35 in the control group). Analysis showed a
      decrease in the number of unprotected anal sex acts (p = 0.029) and an increase
      in the number of answers favoring prevention in the intervention group. The
      results indicate that the study group was responsive to a safer sex operative
      group intervention. Further research is necessary to evaluate the feasibility of
      this prevention approach as a public health strategy, including other social
      groups.

PMID- 17435893
TI  - [Family planning services under the Family Health Program in Brazil].
AB  - This evaluative study was performed in eight counties in Ceara State, Brazil,
      from July to September 2003. Data were collected through interviews with 29
      nurses and 50 users of the Family Health Program (FHP), besides observations at
      health units. The aim was to identify the nature of family planning services and
      verify the existence of barriers to services and provision of contraceptives with
      a view towards ensuring an appropriate services network. Five styles of services
      were identified, although none followed a formal protocol, which raises a legal
      and ethical dilemma regarding prescription of contraceptives by nurses; delivery
      of contraceptive methods requires a monthly return visit by users due to
      excessive and unnecessary technical requirements that create barriers to access
      by users; and there is a lack of appropriate services, with nurse- and doctor
      centered treatment and lack of partnership with other reproductive health
      services or community groups. Future studies should be designed to identify
      distinct dynamics in the FHP that innovate in family planning, as well as to
      define the legal and ethical framework for nurses to prescribe the methods.

PMID- 17435894
TI  - [Reliability of a questionnaire to assess food safety knowledge, perceptions, and
      practices among outpatients with human immunodeficiency virus].
AB  - HIV-positive patients are at increased risk of acquiring infections, particularly
      those related to water and food. The risk could be reduced by educational
      interventions in the clinical setting related to food safety for the prevention
      of food-borne diseases. The current study aimed to analyze food safety knowledge,
      perceptions, and practices among HIV-positive outpatients. A questionnaire was
      organized with five behavioral areas (cross contamination; personal hygiene;
      household hygiene; temperature control; and control of unsafe foods). The test
      retest procedure demonstrated the questionnaire's reliability. Kappa values
      varied among the questions: high for 84.6% (33); moderate for 12.8% (5); and low
      for 2.5% (1). Based on the results, the instrument showed good reliability for
      most of the questions and can be used for surveys on food safety in HIV-positive
      outpatients.

PMID- 17435896
TI  - Risk factors involved in performing lobectomy to treat bronchial carcinoma.

PMID- 17435897
TI  - Silicosis (still) among us.

PMID- 17435898
TI  - Prognostic factors for complications following pulmonary resection: pre-albumin
      analysis, time on mechanical ventilation, and other factors.
AB  - OBJECTIVE: To determine whether pre-operative nutritional status and post
      operative time on mechanical ventilation, as well as others factors, are
      correlated with post-operative complications (general or pulmonary) in patients
      undergoing elective thoracic surgery. METHODS: A prospective study was conducted,
      involving 71 patients undergoing elective pulmonary resection. The data collected
      pre-operatively included gender, age, smoking status, pre-albumin level,
      lymphocyte count, and body mass index. The peri-operative data included type of
      surgery and surgical time, as well as post-operative time on mechanical
      ventilation. RESULTS: Post-operative complications were found to correlate with
      low pre-albumin concentration, type of resection, surgical time, and post
      operative time on mechanical ventilation. Surgical time and post-operative time
      on mechanical ventilation were also implicated in the post-operative pulmonary
      complications observed in 22 (30.99%) of the patients studied. CONCLUSION: Our
      results suggest that pre-albumin concentration, type of surgery and surgical
      time, as well as post-operative time on mechanical ventilation, serve as
      predictive indices of post-operative complications in patients undergoing
      elective pulmonary resection. In the analysis of the post-operative pulmonary
      complications, statistically significant correlations were found between such
      complications and increases in surgical time or post-operative time on mechanical
      ventilation.

PMID- 17435900
TI  - Analysis of 39 cases of idiopathic chronic interstitial pneumonia.
AB  - OBJECTIVE: To make a retrospective analysis of lung biopsy samples obtained from
      patients diagnosed with chronic idiopathic interstitial pneumonia, as defined in
      the American Thoracic Society/European Respiratory Society classification system
      made public in 2000. METHODS: Samples from 252 open-lung biopsies of patients
      with interstitial lung disease, all performed between 1977 and 1999, were
      reviewed, and 39 cases of idiopathic interstitial lung disease were selected and
      re-evaluated by two pathologists in accordance with the American Thoracic
      Society/European Respiratory Society classification system. RESULTS: Among those
      39 cases, the diagnoses were maintained in 28 (71.8%). A new pathologic entity,
      nonspecific interstitial pneumonia, was included in the reclassification, and
      overlapping patterns were observed in 6 cases. Of the 28 cases in which the
      diagnosis of chronic idiopathic interstitial pneumonia remained unchanged,
      idiopathic pulmonary fibrosis was accompanied by cryptogenic organizing pneumonia
      in 4, cryptogenic organizing pneumonia was accompanied by nonspecific
      interstitial pneumonia in 1, and desquamative interstitial pneumonia was
      accompanied by nonspecific interstitial pneumonia in 1. All cases of idiopathic
      pulmonary fibrosis were confirmed, although 3 of those were found to be
      accompanied by cryptogenic organizing pneumonia. Virtually all prior diagnoses
      were maintained in the review of the biopsy samples (p > 0,05). CONCLUSION: The
      American Thoracic Society/European Respiratory Society system of classifying
      interstitial lung disease is a useful tool for pathologists who deal with lung
      biopsies.

PMID- 17435899
TI  - Lobectomy for treating bronchial carcinoma: analysis of comorbidities and their
      impact on postoperative morbidity and mortality.
AB  - OBJECTIVE: To analyze the impact that comorbidities have on the postoperative
      outcomes in patients submitted to lobectomy for the treatment of bronchial
      carcinoma. METHODS: A retrospective study of 493 patients submitted to lobectomy
      for the treatment of bronchial carcinoma was conducted, and 305 of those patients
      met the criteria for inclusion in the final study sample. The surgical technique
      used was similar in all cases. The Torrington-Henderson scale and the Charlson
      scale were used to analyze comorbidities and to categorize patients into groups
      based on degree of risk for postoperative complications or death. RESULTS: The
      postoperative (30-day) mortality rate was 2.9%, and the postoperative
      complications index was 44%. Prolonged air leakage was the most common
      complication (in 20.6%). The univariate analysis revealed that gender, age,
      smoking, neoadjuvant therapy and diabetes all had a significant impact on the
      incidence of complications. The factors found to be predictive of complications
      were body mass index (23.8 +/- 4.4), forced expiratory volume in one second (74.1
      +/- 24%) and the ratio between forced expiratory volume in one second and forced
      vital capacity (0.65 +/- 0.1). The scales employed proved efficacious in the
      identification of the risk groups, as well as in drawing correlations with
      morbidity and mortality (p = 0.001 and p < 0.001). In the multivariate analysis,
      body mass index and the Charlson index were found to be the principal
      determinants of complications. In addition, prolonged air leakage was found to be
      the principal factor involved in mortality (p = 0.01). CONCLUSION: Reductions in
      forced expiratory volume in one second, in the ratio between forced expiratory
      volume in one second and forced vital capacity, and in body mass index, as well
      as a Charlson score of 3 or 4 and a Torrington-Henderson score of 3, were
      associated with a greater number of postoperative complications in patients
      submitted to lobectomy for the treatment of bronchial carcinoma. Air leakage was
      found to be strongly associated with mortality.

PMID- 17435901
TI  - Location of lung carcinoma in relation to the smoking habit and gender.
AB  - OBJECTIVE: To analyze the locations of lung carcinomas in relation to patient
      gender and smoking status. METHODS: In order to test the hypothesis that lung
      carcinoma location (upper or lower lobe; left or right side) is correlated with
      smoking status and gender, we conducted a retrospective study of 697 patients
      with bronchogenic carcinoma treated at the Pulmonology-Oncology Outpatient Clinic
      of the Federal University of Sao Paulo. RESULTS: We found that the bronchogenic
      carcinomas occurring in smokers were more frequently located in the upper lobes,
      whereas those occurring in nonsmokers were more frequently located in the lower
      lobes. In women, the neoplasms were more often seen in the lower lobes,
      especially in nonsmokers. Based on the available data, there were no differences
      in terms of the side affected (left or right). CONCLUSION: Overall, bronchogenic
      carcinomas are predominantly found in the upper lobes. However, in nonsmokers,
      they occur more frequently in the lower lobes. In females, bronchogenic
      carcinomas present a tendency to occur more often in the lower lobes.

PMID- 17435902
TI  - Progressive massive fibrosis in silica-exposed workers. High-resolution computed
      tomography findings.
AB  - OBJECTIVE: To evaluate the radiological characteristics of conglomerate masses
      using high-resolution computed tomography of the chest. METHODS: From among the
      patients treated between 1986 and 2004 at the Antonio Pedro University Hospital,
      75 patients with silicosis and massive fibrosis, most working in the field of
      sandblasting, were selected for study. These patients were submitted to a
      clinical evaluation, chest X-ray and high-resolution computed tomography of the
      chest. RESULTS: In more than half of the patients with accelerated silicosis, the
      chest X-ray revealed large type B and C opacities, denoting the severity of the
      disease in those patients. In 1 case, a unilateral mass simulating lung cancer
      was observed. High-resolution computed tomography scans of the chest were
      acquired for 44 patients. In most cases (88.6%), the masses were located in the
      superior and posterior thirds of the lung. Common findings within the masses
      included air bronchograms (in 70.4%) and calcifications (in 63.6%). A history of
      tuberculosis was reported by 52% of the patients. CONCLUSION: In the vast
      majority of cases, the masses were bilateral, predominantly located in the
      superior and posterior regions of the lung, featuring air bronchograms and
      interposed calcifications. Concomitant calcification of the mediastinal and hilar
      lymph nodes was another common finding. Exposure to high concentrations of dust
      and having a history of tuberculosis were considered significant risk factors for
      the development of progressive massive fibrosis.

PMID- 17435903
TI  - Epidemiological aspects of human immunodeficiency virus/tuberculosis co-infection
      in Ribeirao Preto, Brazil from 1998 to 2003.
AB  - OBJECTIVE: This study aimed to characterize the epidemiological profile of
      tuberculosis cases reported in the city of Ribeirao Preto between 1998 and 2003,
      according to patient HIV status, gender, age bracket and treatment outcome.
      METHODS: This was a descriptive epidemiological study that employed the Brazilian
      National Tuberculosis Notification Database as an instrument of data collection.
      The study sample consisted of all cases of human immunodeficiency
      virus/tuberculosis co-infection occurring in residents of Ribeirao Preto and
      reported between 1998 and 2003. RESULTS: During this period, 1273 new cases of
      tuberculosis were reported, 377 of which were in HIV-positive individuals, for a
      co-infection rate of 30%. Of the cases of co-infection, 76% were in men, and the
      majority occurred in individuals in the 20-59 age bracket. In terms of treatment
      outcome, cure was achieved in 52%, treatment abandonment was reported in 11%, and
      death occurred in 32%. The predominant clinical form of tuberculosis was the
      pulmonary form, which accounted for 58% of the cases. CONCLUSION: A high
      prevalence of co-infection was observed in the community studied. The treatment
      outcomes seen among the cases in our study sample underscore the need to adopt
      special strategies to monitor this clientele. Comparing the cases of tuberculosis
      in isolation with the cases of co-infection, no gender-related or age-related
      differences were observed.

PMID- 17435904
TI  - Characteristics of elderly tuberculosis patients in Recife, Brazil: a
      contribution to the tuberculosis control program.
AB  - OBJECTIVE: To describe the demographic characteristics, everyday habits, socio
      economic conditions, clinico-epidemiological profiles and access to health care
      services among the elderly patients with tuberculosis diagnosed and treated in
      the city of Recife, Brazil, comparing them to those observed in young adults with
      tuberculosis. METHODS: A case-control type strategy was used to evaluate a cohort
      of patients with tuberculosis, all of whom were treated in public health care
      facilities in Recife between May of 2001 and July of 2003. RESULTS: The final
      cohort consisted of 1127 patients: 136 elderly patients (cases) and 991 young
      adults (controls). In both groups, males predominated, and the most common form
      of tuberculosis was the pulmonary form. Alcoholism was more common in the control
      group, whereas illiteracy was more common in the case group. There were fewer
      complaints of cough, sweats and chest pain among the patients in the case group
      than among those in the control group. Serological testing for the human
      immunodeficiency virus was performed in only 29 patients (2.6%). The percentage
      of positive sputum smear microscopy results, as well as that of positive
      cultures, was higher in the controls. Prior to being diagnosed with the disease,
      patients in both groups had sought treatment at more than two health care
      facilities and had waited more than two months (after first seeking treatment).
      The elderly patients presented higher indices of cure and were more often
      compliant with the treatment regimen, yet presented higher mortality rates.
      CONCLUSION: In the population studied, the elderly presented less cough, fewer
      episodes of night sweats and less chest pain, as well as less often presenting
      positivity on complementary exams. Nevertheless, the mortality rate was higher
      among the elderly patients than among the young adult patients. Elderly patients
      with tuberculosis constitute a population that should be given special attention
      in public health care facilities.

PMID- 17435905
TI  - Deaths attributed to multiple causes and involving tuberculosis in the state of
      Rio de Janeiro Brazil between 1999 and 2001.
AB  - OBJECTIVE: To evaluate deaths attributed to multiple causes in which tuberculosis
      was one of the causes listed. METHODS: All deaths among residents of the state of
      Rio de Janeiro, Brazil, occurring between 1999 and 2001 and for which the death
      certificate mentioned tuberculosis, were investigated. The World Health
      Organization guidelines were used in characterizing the underlying and associated
      (non-underlying) causes of death. RESULTS: In deaths from tuberculosis,
      conditions related to its natural history were the principal associated causes,
      together with alcoholism and diabetes. In approximately three-fifths of all
      deaths for which tuberculosis was listed as an associated cause, the underlying
      cause of death was acquired immunodeficiency syndrome. High proportion of ill
      defined causes of death, low values found for the number of causes informed per
      death certificate and for TB as an associated cause point towards a certain
      degree of underestimation of the actual number of TB-related deaths in Rio de
      Janeiro State. CONCLUSION: The study shows that the rates of tuberculosis-related
      mortality in the state of Rio de Janeiro, calculated based on the number of times
      tuberculosis was listed as a cause of death (underlying or associated), are the
      highest in the country. Epidemiological studies of mortality are recommended as a
      means of guiding the activities of the tuberculosis control program.

PMID- 17435906
TI  - Evolution of tuberculosis-related mortality in Fortaleza, Brazil from 1980 to
      2001.
AB  - OBJECTIVE: To evaluate the evolution of tuberculosis-related mortality, as well
      as gender-related and age-related tendencies, in the city of Fortaleza, Brazil.
      METHODS: A descriptive study, based on secondary data, was conducted. All deaths
      from tuberculosis occurring among residents of Fortaleza in the 1980-2001 period
      and reported to the Ministry of Health via the Mortality Database were included.
      The evolution of tuberculosis-related mortality was compared with that of overall
      mortality and with that of mortality from all infectious diseases. The tendencies
      of the coefficients of overall mortality and of tuberculosis-related mortality,
      adjusted and unadjusted for age and gender, were calculated for the study period.
      RESULTS: The coefficients of overall mortality and of tuberculosis-related
      mortality presented decreasing tendencies. The coefficient of tuberculosis
      related mortality presented a decreasing tendency in individuals = 19 years of
      age (y = -0.0906x + 2.5133), from 20 to 59 years of age (y = -0.414x + 12.29) and
      60 years of age (y = -1.2494x + 40.289), as well as in males (y = -0.3175x +
      10.971) and females (y = -0.1933x + 6.8051). CONCLUSION: Despite displaying a
      decreasing tendency, the coefficient of tuberculosis-related mortality remains
      high.

PMID- 17435907
TI  - Investigation of tuberculosis contacts in the tuberculosis control program of a
      medium-sized municipality in the southeast of Brazil in 2002.
AB  - OBJECTIVE: This study aimed to describe the investigation of tuberculosis
      contacts enrolled in the Tuberculosis Control Program of the municipality of Sao
      Jose do Rio Preto, Brazil in 2002. METHODS: A descriptive study was conducted
      using secondary data obtained from the Tuberculosis Notification Database, as
      well as charts and registries compiled by the Sao Jose do Rio Preto Tuberculosis
      Control Program in 2002. RESULTS: A total of 166 household tuberculosis contacts
      were enrolled in the Program. Of those, 82 were male, and 84 were females. The
      incidence of tuberculosis was highest (70%) in the 15 to 59 age bracket: 42
      (25.3%) of the cases occurred in individuals from 0 to 19 years of age; 73 (44%)
      in those from 20 to 49; and 44 (25.5%) in those 50 or over. In terms of their
      relationship with the index patient, 41 (24.7%) were children; 29 (17.5%) were
      partners; 22 (13.2%) were siblings, and 15 (9.1%) were mothers. The following
      tests were requested: (in 12%) sputum smear microscopy, culture or both; (in
      100%) chest X-ray, revealing 2 suspected cases of pulmonary tuberculosis and 5
      cases of other diseases; (in 7.2%) tuberculin skin test, the results of which
      showed that 4.2% were nonreactors, and that 1.2% presented an induration of 8 mm.
      Among the contacts examined, the disease was detected in 3 (1.8%). CONCLUSION:
      There is no systematization in the monitoring of individuals who are in contact
      with tuberculosis patients.

PMID- 17435908
TI  - Tuberculosis in a psychiatric hospital in the state of Goias, Brazil.
AB  - OBJECTIVE: To investigate the prevalence of infection, disease and eventual
      institutional outbreak of tuberculosis in a psychiatric hospital using the PPD
      test, as well as testing for mycobacteria in material collected from the
      respiratory tree and using molecular tracking technique based on insertion
      sequence 6110 (IS6110). METHODS: Between February and August of 2002, PPD tests
      were given to 74 inpatients and 31 staff members at a psychiatric hospital in the
      city of Rio Verde, located in the state of Goias, Brazil. In addition,
      respiratory tree material collected from the inpatients was submitted to testing
      for Mycobacterium tuberculosis. RESULTS: Among the patients analyzed,
      mycobacteria were isolated from five (6.8%): four identified as M. tuberculosis
      and one as M. chelonae. The M. tuberculosis isolates were sensitive to isoniazid
      and rifampicin, and, when submitted to the restriction fragment length
      polymorphism/IS6110 technique, presented unique genetic profiles, totally
      distinct from one another, suggesting that all of the tuberculosis cases were due
      to endogenous reactivation. It was not possible to characterize this group of
      cases as an institutional outbreak. Performing the two-step tuberculin test in
      the patients, the infection rates were 23% and 31%, compared with 42% among staff
      members, who were submitted to the one-step test. CONCLUSION: The results
      indicate a high incidence of tuberculosis infection among inpatients and hospital
      staff, as well as a high occurrence of the disease among inpatients.

PMID- 17435909
TI  - The influence of genetics on nicotine dependence and the role of pharmacogenetics
      in treating the smoking habit.
AB  - Despite the considerable efforts made in the fight against smoking in the last
      decades, there are still substantial numbers of people who, in full knowledge of
      the health hazards, begin smoking or continue smoking. Recent studies have
      focused on the genetic bases of the nicotine addiction. Various genetic
      polymorphisms have been associated with smoking. However, environmental factors
      have also been shown to play a role. In this review, we present some of the
      principal data collected in genetic studies of smoking behavior. The results
      obtained through this line of research will eventually aid clinicians in
      individualizing the type, dosage and duration of treatment for patients with
      nicotine dependence in accordance with the genotype of each smoker, thereby
      maximizing the efficacy of the proposed treatment regimen.

PMID- 17435910
TI  - Functionality of patients with chronic obstructive pulmonary disease: energy
      conservation techniques.
AB  - Chronic obstructive pulmonary disease is a progressive and debilitating disease
      that is typically diagnosed only after a long period of gradual worsening.
      Dyspnea is the symptom that most often interferes with the execution of
      professional, family, social and daily-life activities of patients with chronic
      obstructive pulmonary disease. Such limitations can lead to a sedentary lifestyle
      and worsen overall quality of life. This article aims to address the functional
      limitations these patients deal with in carrying out their daily-life activities,
      establishing guidelines that health professionals can use to help their patients
      achieve maximum functionality. Guidelines for the use of energy conservation
      techniques are widely used in pulmonary rehabilitation programs. However, these
      guidelines should also be used in outpatient clinics and hospitals. A great
      number of human activities involve the legs and arms. The arms are involved in
      virtually all everyday activities--from the most simple to the most complex. Some
      studies have shown that upper-body exercises in which the arms are not supported
      cause thoracoabdominal asynchrony and dyspnea in shorter times and with less
      oxygen consumption than in exercises involving the legs. Even simple tasks can
      result in high oxygen consumption and minute ventilation, which accounts for the
      sensation of dyspnea reported by the patients. In view of these facts, it is
      appropriate to evaluate the impact that such incapacity has on daily life in
      patients with chronic obstructive pulmonary disease. Techniques of energy
      conservation that can be used as tools to minimize the discomfort of such
      patients are herein discussed, and those considered most appropriate are
      highlighted.

PMID- 17435911
TI  - Postinfectious bronchiolitis obliterans accompanied by pulmonary hemosiderosis in
      childhood.
AB  - In the present report, we describe an unusual presentation of post-infectious
      bronchiolitis obliterans accompanied by pulmonary hemosiderosis in a nine-year
      old boy with persistent respiratory symptoms subsequent to an episode of acute
      bronchiolitis occurring at the age of seven months. After the episode, the
      persistent respiratory symptoms worsened significantly, and, by the age of seven,
      the patient began to have difficulty breathing after minimal exertion. Computed
      tomography of the chest presented findings consistent with bronchiolitis
      obliterans. Open lung biopsy revealed numerous hemosiderin-laden macrophages, as
      well as other findings consistent with bronchiolitis obliterans. Pulmonary
      hemosiderosis can occasionally be accompanied by bronchiolitis obliterans in
      children with severe sequelae after an episode of viral infection.

PMID- 17435912
TI  - Pulmonary and cutaneous nocardiosis in a patient treated with corticosteroids.
AB  - Nocardiosis is a localized or disseminated infection caused by gram-positive
      bacteria of the genus Nocardia. The infection most commonly affects the lungs,
      skin and central nervous system. Nocardiosis principally occurs in individuals
      with cellular immunodeficiency and should be considered in the differential
      diagnosis when such individuals present respiratory, cutaneous or neurological
      alterations. Herein, we report a case of pulmonary and cutaneous nocardiosis in a
      patient receiving oral corticosteroids to treat bronchiolitis obliterans
      accompanied by organizing pneumonia of unknown origin. After long-term treatment
      with sulfamethoxazole-trimethoprim, the clinical and radiological profile
      improved.

PMID- 17435913
TI  - Exogenous lipoid pneumonia: importance of clinical history to the diagnosis.
AB  - Lipoid pneumonia is a rare disease resulting from the micro-aspiration of lipid
      formulations. Making a diagnosis of lipoid pneumonia requires a high degree of
      clinical suspicion. Herein, we report the case of a female patient with a history
      of breast cancer, presenting progressive dyspnea and cough, together with
      radiological findings of bilateral pulmonary infiltrate. The working diagnosis of
      lymphangitic carcinomatosis, for which chemotherapy would be indicated, was
      called into question based on the high-resolution computed tomography findings
      and on the fact that the patient had a history of chronic ingestion of laxatives
      containing mineral oil. A lung biopsy confirmed a diagnosis of lipoid pneumonia,
      which should always be considered in patients with diffuse lung disease having
      been exposed to potential causative agents.

PMID- 17435914
TI  - Spontaneous chylothorax associated with light physical activity.
AB  - Chylothorax occurs when there is rupture, laceration or obstruction of the
      thoracic duct, resulting in the release of chyle into the pleural space.
      Chylothorax can occur in cases of congenital lymphatic malformation, lymphoma,
      mediastinal tumor and infectious disease, as well as during surgical procedures
      and after traffic accident-related trauma. It can also be idiopathic. The
      condition presents clinical signs of dyspnea, hypotension, generalized edema and
      cyanosis. The diagnosis is usually made through thoracocentesis, and the
      treatment is conservative. Spontaneous chylothorax is an uncommon form of pleural
      effusion, and its diagnosis should be hypothesized only after all other causes
      have been ruled out. Herein, we describe a case of spontaneous chylothorax
      associated with light physical activity at a fitness center.

PMID- 17435916
TI  - Extreme thinness in models mobilizes eating disorders' researchers and
      specialists.

PMID- 17435917
TI  - What is the meaning of associations between personality traits and anxiety and
      depressive disorders?

PMID- 17435918
TI  - Nurturing resilient children.

PMID- 17435919
TI  - [Suicide: moving away umbrage towards a National Prevention Plan].

PMID- 17435920
TI  - Antipsychotic drugs and metabolic syndrome--can we prevent it?

PMID- 17435921
TI  - Prevalence of mental health problems in children and adolescents from the
      outskirts of Sao Paulo City: treatment needs and service capacity evaluation.
AB  - OBJECTIVE: To estimate the prevalence of mental health problems in children and
      adolescents, with or without considering global impairment, within a low-income
      urban community; to estimate the public service delivery capacity in terms of
      mental healthcare; and to determine the relationship between delivery capacity
      and treatment demand. METHOD: Cross-sectional study. Probabilistic sample of
      clusters including all eligible households (low-income community - Embu,
      Southeastern Brazil). PARTICIPANTS: 479 children and adolescents (aged 6-17
      years; attrition rate: 18.8%). MEASUREMENT: 1) Clinical mental health problems in
      children and adolescents using the Child Behavior Checklist and/or Youth Self
      Report total problem scales; 2) Global impairment: positive score in the Brief
      Impairment Scale (total score > 15.5); 3) Care service capacity: total number of
      cases annually seen by psychologists/psychiatrists in the health, education,
      juvenile justice, and child welfare sectors. RESULTS: Prevalence of mental health
      problems in children and adolescents: 24.6% (20.7-28.5) without considering
      global impairment; 7.3% (5.0-9.6) with global impairment (cases in need of
      treatment). Current annual service capacity can only provide care for 14.0% of
      impaired cases; approximately seven years would be necessary for all to be
      treated. CONCLUSIONS: Mental health problems in children and adolescents are
      frequent in the studied community, and the current structure of the community's
      public service system is not prepared to treat impaired cases in an adequate
      timeframe.

PMID- 17435922
TI  - Validity and limitations of the Brazilian version of the Composite International
      Diagnostic Interview (CIDI 2.1).
AB  - OBJECTIVE: To study the concurrent validity of the Brazilian Composite
      International Diagnostic Interview 2.1 using as gold standard the clinical
      diagnoses based on the ICD-10 criteria and the Longitudinal, Expert, All Data
      (LEAD) procedure. METHOD: The sample was composed of 185 subjects selected at
      psychiatric hospitals, psychiatric outpatient units, the community, and primary
      care services. These individuals were intentionally selected according to 9
      diagnostic groups. INSTRUMENTS: Composite International Diagnostic Interview
      (CIDI-core) version 2.1 (paper-and-pencil) administered by 16 trained
      interviewers. ANALYSIS: concurrent validity of diagnoses of the Composite
      International Diagnostic Interview 12-month. RESULTS: Values found for
      sensitivity and specificity in each diagnosis were: alcohol-related disorders
      (79.5%/97.2%); psychoactive substance-related disorders (77.3%/100%);
      schizophrenia and other psychotic disorders (28.6%/93.9%); manic episode and
      bipolar affective disorder (38.9%/96.4%); depressive disorder (82.5%/ 93.8%);
      phobic-anxiety disorder (80.6%/93.5%); obsessive-compulsive disorder
      (18.2%/98.9%); somatoform disorder (41.7%/90.8%); eating disorder (45.5%/100.0%).
      CONCLUSION: The Composite International Diagnostic Interview proved to be valid
      for diagnoses of alcohol-related disorders, psychoactive substance-related
      disorders, depressive disorder and phobic-anxiety disorder. The probable
      explanations for the poor performance for the other diagnoses were: necessity of
      some clinical judgement by the lay interviewer; difficulty to use the Probe Flow
      Chart; interviewees' difficulty of understanding; and lack of mechanisms to
      certify the veracity of the information.

PMID- 17435923
TI  - The use of a manual-driven group cognitive behavior therapy in a Brazilian sample
      of obese individuals with binge-eating disorder.
AB  - OBJECTIVE: To assess the effectiveness of a manual-based cognitive behavior
      therapy adapted to a group format in a sample of Brazilian obese subjects with
      binge-eating disorder. METHOD: In an open trial, 21 obese subjects with binge
      eating disorder received a group cognitive-behavioral therapy program. Changes in
      binge-eating frequency, weight, body shape concerns, and depressive symptoms were
      compared between baseline and the end of the study. RESULTS: The mean frequency
      of binge-eating episodes significantly decreased from baseline to post-treatment
      (p < 0.001), with a binge eating remission rate of 76.1% at the end of the trial.
      Depressive symptoms and body shape concern also improved (p < 0.001). In
      addition, weight loss was statistically and clinically significant. CONCLUSION:
      The use of this adapted manual-based cognitive behavior therapy in this sample
      resulted in a marked improvement in binge-eating, weight, body shape concern, and
      depressive symptoms related to binge-eating disorder.

PMID- 17435925
TI  - Personality traits spectrum in panic disorder and major depression.
AB  - OBJECTIVE: Our aim was to identify the personality traits in patients with panics
      disorder, major depression and with both disorders (comorbidity). METHOD:
      Diagnoses were made with the Structured Clinical Interview for DSM-IV before the
      treatment, and the personality evaluation with the Maudsley Personality Inventory
      was made during the follow-up. Four groups were analyzed: a control group (n =
      30), a major depression without panic disorder group (n = 45); a panic disorder
      without major depression group (n = 56) and a comorbidity group (n = 21), with
      major depression and panic disorder, simultaneously. RESULTS: All disorder groups
      had significantly higher neuroticism means when compared to the control group.
      The highest mean was in the comorbidity group, followed by the major depression
      group and the panic disorder group. The difference of neuroticism means between
      the comorbidity group and the panic disorder group also reached statistical
      significance. The lowest extraversion mean was in the comorbidity group, followed
      by the major depression group, the panic disorder group, and the control group.
      Compared to normal controls, extraversion was significantly low in the
      comorbidity and major depression groups. CONCLUSION: In our sample, there was a
      continuum of personality traits between panic disorder and major depression and,
      the co-occurrence of these disorders was associated with accentuated personality
      traits.

PMID- 17435924
TI  - Crack users, sexual behavior and risk of HIV infection.
AB  - OBJECTIVE: To compare a sample of injecting cocaine users and crack users,
      assessing sexual behavior, risk for infection by HIV and its seroprevalence.
      METHOD: 109 injecting cocaine users and 132 crack users were assessed, using the
      World Health Organization questionnaire from the expanded "Cross-Site Study of
      Behaviors and HIV Seroprevalence among Injecting Drug Users" and HIV serology.
      Data were assessed by Multiple Correspondences Analysis. RESULTS: Crack users
      showed less time of drug consumption when compared to the injecting cocaine
      users. Despite this fact, they had higher rates of risky sexual activity,
      differences in poli-consumption of drugs, and higher rates of involvement in
      illegal issues. HIV seroprevalence among crack users, although lower than for
      injecting cocaine users (7% vs. 33%) is high when compared to the general
      population at the same age. CONCLUSIONS: Sexual behavior of crack users in the
      studied sample may be considered a risk factor for HIV infection. Crack users
      have access to information on HIV/ AIDS, but do not make use of it to change risk
      behaviors that may expose them to HIV infection and dissemination. HIV
      seroprevalence among crack users (7%) is concerning, which makes it necessary to
      create preventive strategies for HIV infection and dissemination that are
      specifically directed toward this population.

PMID- 17435926
TI  - Polypharmacy and suicide attempts in bipolar disorder.
AB  - OBJECTIVE: The aim of this study was to assess the association between suicide
      attempts and the use of multiple drugs in patients with bipolar disorder. METHOD:
      One hundred sixty-nine bipolar disorder outpatients diagnosed using the DSM-IV
      Structured Clinical Interview were included. Demographic and socioeconomic data,
      number of medications currently in use, history of suicide attempts, number of
      years undiagnosed, age of onset and current psychiatric co-morbidities were
      assessed using a structured questionnaire and DSM-IV criteria. The main outcome
      measure was the number of psychotropic drugs currently in use. RESULTS:
      Approximately half of all patients (48.5%) presented a history of suicide
      attempt; 84% were using more than one medication, and 19% were using more than
      three drugs. The most frequent combinations of drugs used by these patients were:
      lithium + valproate (17%); lithium + antipsychotics (10%); lithium + valproate +
      antipsychotics (9%); and antidepressants + any drug (6%). The number of suicide
      attempts was associated with the use of multiple drugs. CONCLUSIONS: Our findings
      support the notion that the use of combination therapy in bipolar disorder may be
      related to severity of the BD, such as number of suicide attempts.

PMID- 17435927
TI  - Brazilian female crack users show elevated serum aluminum levels.
AB  - OBJECTIVE: There is no information in the literature on the impact of crack
      smoking using crushed aluminum cans as makeshift pipes, a common form of crack
      use in Brazil. Since aluminum intake is associated with neurological damage, we
      measured serum aluminum levels in crack smokers. The objective of this study was
      to ascertain the levels of aluminum in crack users who smoke on makeshift
      aluminum pipes. METHOD: 71 female crack smokers, their mean age being 28.0 (+/-
      7.7), provided information about their drug use, and had blood samples tested for
      serum aluminum level. RESULTS: 56 (79%) subjects smoked crack from crushed can
      pipes, while 15 (21%) smoked from other containers. Fifty-two (73.2%) out of the
      71 subjects presented a serum aluminum level of 2 microg/l and 13 (18.3%) had a
      serum aluminum level of 6 microg/l cut-off point, which is above the reference
      value. When compared to non-drug users matched by their mean age and gender, they
      had similar median values and interquartile ranges for serum aluminum level [3 (2
      4.6) for crack smokers; 2.9 (1.6-4.1) for controls], but with different means and
      standard deviations (4.7 +/- 4.9 and 2.9 +/- 1.7, respectively). DISCUSSION:
      Crack smokers have high serum aluminum level, but we are unsure of its complete
      association with aluminum cans. Further studies are needed. If such association
      is proven true in future research, further issues will be raised in dealing with
      this important disorder, including proper planning and evaluation of public
      health policies in this area.

PMID- 17435928
TI  - Is psychiatric reform a strategy for reducing the mental health budget? The case
      of Brazil.
AB  - OBJECTIVE: To investigate trends in the provision of mental health services and
      financing in Brazil. METHOD: Data from DATASUS (the Brazilian Unified Health
      Computerized System) with free access in the web were collected regarding the
      number of beds, the development of new community centers, the number of mental
      health professionals, and costs involved from 1995 to 2005. RESULTS: In ten
      years, the number of psychiatric beds decreased 41% (5.4 to 3.2 per 10,000
      inhabitants) while community services have increased nine-fold (0.004 to 0.037
      per 10,000 inhabitants). Psychologists and social workers have accounted for
      three and two-fold, respectively, as much hirings as psychiatrists. Psychiatric
      admissions accounted for 95.5% of the budget in 1995 and 49% in 2005, and the
      expenses with community services and medication have increased 15% each. As a
      whole, the expenses in mental health decreased by 26.7% (2.66 to 1.95 US$ per
      capita). CONCLUSION: There has been a clear switch from hospital to community
      psychiatric care in Brazil, where the system can now provide a diversity of
      treatments and free access to psychotropics. However, the coverage of community
      services is precarious, and the reform was not accompanied by an increased public
      investment in mental health. The psychiatric reform is not a strategy for
      reducing costs; it necessarily implies increasing investments if countries decide
      to have a better care of those more disadvantaged.

PMID- 17435929
TI  - Family Burden Interview Scale for relatives of psychiatric patients (FBIS-BR):
      reliability study of the Brazilian version.
AB  - OBJECTIVE: Psychiatric deinstitutionalization resulted in greater involvement of
      families in daily care of patients. Family caregivers burden has been described
      by international researches. In Brazil very few studies investigated family
      burden with validated scales, perhaps due to the restrict availability of scales
      to measure this construct. The present study examined the reliability of the
      Brazilian version of the Family Burden Interview Schedule. METHOD: Scale
      reliability was assessed through its internal consistency and temporal stability.
      A sample of 243 family caregivers of psychiatric patients attending public
      outpatient services were interviewed with the scale. Socio-demographic data were
      collected with a standardized form. A sub-sample of 42 relatives participated in
      a re-test, after 3 weeks, for assessment of the scale temporal stability.
      RESULTS: Cronbach alpha coefficients ranged from 0.58 to 0.90 for global and
      domains scores. Pearson correlation coefficients and intra-class correlation
      coefficients for test and retest ranged from 0.54 to 0.90. DISCUSSION: Results
      for internal consistency were similar to the original scale. Four subscales
      presented alpha coefficients superior to the original ones. The temporal
      stability cannot be compared because this analysis was not performed for the
      original scale. CONCLUSION: The Brazilian version of the scale had good
      psychometric properties of temporal stability and internal consistency.

PMID- 17435930
TI  - Suicide risk among inpatients at a university general hospital.
AB  - OBJECTIVE: To estimate the proportion of inpatients at a university general
      hospital who are at risk of committing suicide. METHOD: A random sample of 253
      patients (57% males) aged 18 years old or older, admitted to surgical and
      clinical wards, was assessed using the the Mini International Neuropsychiatric
      Interview, which has a section that evaluates the risk for suicide. Uni- and
      multivariate analyses were performed. RESULTS: There were 58 (23%) patients with
      a risk for suicide, 13 (5% of total) of whom presented a high risk. The
      prevalence of suicide risk was greater in young adult patients, those with no
      matrimonial relationship and those diagnosed with major depression (univariate
      analysis, Chi-squared test; p = 0.01, 0.03 and 0.0001, respectively). The
      multivariate analysis revealed that the risk for suicide in individuals younger
      than 30 years old was two fold higher than in those individuals between the ages
      of 30 and 59 years (OR = 0.45, 95% CI = 0.22-0.93; p = 0.03) and four fold
      greater than in those who were 60 years old or older (OR = 0.25, 95% CI = 0.1
      0.64; p = 0.004). CONCLUSION: When young adults are admitted to general hospitals
      they should receive special attention due to their suicidal potential.

PMID- 17435931
TI  - [Pathological love: is it a new psychiatric disorder?].
AB  - OBJECTIVE: The pathological love is characterized by being a behavior of taking
      care and paying attention to the beloved partner in a way which is repetitive and
      careless of control in an amorous relationship. Although the available data is
      comprised of case studies, such condition (which is distinguished itself from
      erotomania or delusional love) seems not to be rare. METHOD: We reviewed the
      available literature on the clinical characteristics of pathological love (PL),
      using the Medline, Lilacs and PsychoINFO databases. DISCUSSION: It was verified
      that low self-esteem, feelings of anger and affectionate deprivation, and
      emotional distress can be important psychological factors in the evolvement of
      such clinical diagnosis. Similarly, some family factors could be associated with
      it, such as substance abuse, and history of physical and/or emotional negligence
      during childhood. CONCLUSIONS: The progress of research may bring broader
      precision on the clinical, etiologic and comorbid features. Thus, this woud be
      favoring an effetive approach to the bearer, adding a potential repercussion on
      the affective life of a significant number of people.

PMID- 17435932
TI  - [Neuroanatomical basis of behavior: history and recent contributions].
AB  - Considering the most recent contributions, the limbic cortical areas, originally
      known as the greater limbic lobe, besides the cingulated and the parahippocampal
      gyri also includes the insula and the posterior orbital cortex. In contrast to
      the nonlimbic cortical areas that project to the basal ganglia (particularly over
      the dorsal aspects of the striatum, constituted by the caudate nucleus and by the
      putamen), the limbic cortical areas are characterized by projecting to the
      hypothalamus and also to the ventral striatum (particularly to the nucleus
      accumbens). Once all the striatum projects to the globus pallidus which projects
      to the thalamus and then to the cortex, generating cortical-subcortical reentrant
      circuits, while the dorsal striatum and pallidum related cortico-subcortical
      loops are involved with motor activities, the ventral cortical-striatal-pallidal
      system is particularly related with behavior functions. The extended amygdala
      (central medial amygdala, stria terminalis or dorsal component, ventral
      component, and bed nucleus of stria terminalis) receives inputs primarily from
      the limbic cortical areas, is particularly modulated by the prefrontal cortex,
      and receives also direct connections from the thalamus that enables the amygdala
      to generate nonspecific and quick responses through its projections to the
      hypothalamus and to the brainstem. The ventral striatal-pallidal and the extended
      amygdala are then two basal forebrain macro-anatomical systems, that together
      with the basal nucleus of Meynert and with the septal-diagonal band system,
      constitute the main structures that are particularly connected with the limbic
      cortical areas, and that altogether project to the hypothalamus and to the
      brainstem which give rise to the autonomic, endocrine and somatosensory
      components of the emotional experiences, and that regulate the basic activities
      of drinking, eating, and related to the sexual behavior.

PMID- 17435934
TI  - The extinction of conditioned fear: structural and molecular basis and
      therapeutic use.
AB  - OBJECTIVE: Through association, a large variety of stimuli acquire the property
      of signaling pleasant or aversive events. Pictures of a wedding or of a plane
      disaster may serve as cues to recall these events and/or others of a similar
      nature or emotional tone. Presentation of the cues unassociated with the events,
      particularly if repeated, reduces the tendency to retrieve the original learning
      based on that association. This attenuation of the expression of a learned
      response was discovered by Pavlov 100 years ago, who called it extinction. In
      this article we review some of the most recent findings about the behavioral and
      biochemical properties of extinction. RESULTS AND DISCUSSION: It has been shown
      that extinction is a new learning based on a new link formed by the cues and the
      absence of the original event(s) which originated the first association.
      Extinction does not consist of the erasure of the original memory, but of an
      inhibition of its retrieval: the original response reappears readily if the
      former association is reiterated, or if enough time is allowed to pass
      (spontaneous recovery). Extinction requires neural activity, signaling pathways,
      gene expression and protein synthesis in the ventromedial prefrontal cortex
      and/or basolateral amygdala, hippocampus, entorhinal cortex and eventually other
      areas. The site or sites of extinction vary with the task. CONCLUSIONS:
      Extinction was advocated by Freud in the 1920's for the treatment of phobias, and
      is used in cognitive therapy to treat diseases that rely on conditioned fear
      (phobias, panic, and particularly posttraumatic stress disorder). The treatment
      of learned fear disorders with medications is still unsatisfactory although some
      have been shown useful when used as adjuncts to behavioral therapy.

PMID- 17435935
TI  - Comment on "Antidepressant treatment-emergent switch in bipolar disorder: a
      prospective case-control study of outcome".

PMID- 17435933
TI  - [Pharmacotherapy for the treatment of anxiety disorders in children and
      adolescents: a sistematic review].
AB  - Anxiety disorders are very prevalent in children and adolescents, causing serious
      impairments. The pharmacological treatment for these disorders is not much
      investigated in children and adolescents. Thus, there is no consensus about its
      indication. The present study aims to check the efficacy and tolerability of
      drugs used for the treatment of anxiety disorders in children and adolescents in
      the context of evidence based medicine. A systematic literature review was
      carried out in the main databases. In addition, authors were contacted. We found
      seven studies classified as A or B according to criteria established by the
      Cochrane Collaboration. Findings suggest efficacy for selective serotonin
      reuptake inhibitors, insignificant or unfavorable results for benzodiazepines and
      imipramine. Some studies present methodological problems. Methodological
      improvements are needed in futures clinical trials.

PMID- 17435936
TI  - [Alcohol public policies in Brazil: to fight or to cooperate?].

PMID- 17435938
TI  - [Intergenerational transmission of family violence: the role of post-traumatic
      stress disorder].

PMID- 17435939
TI  - Remarks on the paper "Dopamine and social anxiety disorder" by Robinson et al.

PMID- 17435940
TI  - Comments on "Weight gain management in patients with schizophrenia during
      treatment with olanzapine in association with nizatidine".

PMID- 17435941
TI  - [Diogenes, homeless population, antimanicomial movement and cinism].

PMID- 17435943
TI  - Aripiprazole worsening positive symptoms and memantine reducing negative symptoms
      in a patient with paranoid schizophrenia.

PMID- 17435945
TI  - [Physical activity 1 x 0 Mental disorders].

PMID- 17435944
TI  - [Hematological alterations associated to olanzapine use after clozapine-induced
      neutropenia].

PMID- 17435946
TI  - Was the exacerbation of PTSD symptoms after high doses of venlafaxine due to the
      noradrenergic mechanism? A case report.

PMID- 17435950
TI  - Silica, a mineral of unknown but emerging health importance.

PMID- 17435951
TI  - The chemistry of silica and its potential health benefits.
AB  - There is considerable interest in the effects of silica on human health in
      contrast to prior research which focused solely on the toxic effects of inhaled
      crystalline silica. However, multiple forms of silica exist in nature and
      silicon, a component, is the second most prevalent element after oxygen. Silica
      has widespread industrial applications including use as a food additive, i.e.,
      anti-caking agent, as a means to clarify beverages, control viscosity, as an anti
      foaming agent, dough modifier, and as an excipient in drugs and vitamins.
      Chemically, silica is an oxide of silicon, viz., silicon dioxide, and is
      generally colorless to white and insoluble in water. When associated with metals
      or minerals the family of silicates is formed. There are several water soluble
      forms of silica referred collectively to as silicic acid (ortho, meta, di, and
      tri-silicates), which are present in surface and well water in the range of 1-
      100 mg/L. Orthosilicic acid is the form predominantly absorbed by humans and is
      found in numerous tissues including bone, tendons, aorta, liver and kidney.
      Compelling data suggest that silica is essential for health although no RDI has
      been established. However, deficiency induces deformities in skull and peripheral
      bones, poorly formed joints, reduced contents of cartilage, collagen, and
      disruption of mineral balance in the femur and vertebrae. Very little toxicity
      data exist regarding aqueous silica consumption due, in part, to the lack of
      anecdotal reports of toxicity and general presumption of safety. However, a few
      rodent studies have been conducted, which indicate a No Observed Adverse Effects
      Level (NOAEL) of 50,000 ppm (mg/L) for dietary silica. In conclusion, many forms
      of silica exist in nature and compelling data support myriad beneficial effects
      of silica in water.

PMID- 17435953
TI  - A review of body water status and the effects of age and body fatness in children
      and adults.
AB  - BACKGROUND: Most investigations of TBW, ECW and body composition and reports of
      their intra-body relationships were published prior to 1980. Distributional TBW
      and ECW relationships within the body have been considered fixed, but there was
      evidence these relationships were affected by the level of fatness. Body
      composition models based on past findings and assumptions could produce
      inaccurate estimates when the majority of the population is overweight to obese.
      METHODS: TBW and ECW volumes, their proportions of body weight, FFM and percent
      body fat and associations with age are considered in U.S. children and adults.
      This review focuses on studies reporting measured body water volumes from large
      samples except for the national predicted values from NHANES III. RESULTS:
      Measured TBW volumes for children and adults are almost exclusively from whites
      with the exception of the estimated values from NHANES III for non-Hispanic black
      and Mexican-Americans. Mean adult TBW volumes are as much as 9 liters greater
      than those reported prior to 1980. Low mean percentages of TBW%WT reflect the
      greater level of adiposity in children and adults, and this level of adiposity
      affects the value of TBW% FFM. Mean ECW volumes for white adults are 10 to 12
      liters larger than those reported previously. With greater fatness in adults,
      ECW%TBW has increased to near 60%, and this implies that a calculation of FFM
      based on 73% and an ECW%TBW of 25-45% could produce an overestimation but more
      important clinically an underestimation of body fatness. CONCLUSION: There is
      inadequate timely information on measured total and extra-cellular water volumes
      for the population. Available data indicate a coincident increase in body water
      with overweight and obesity, and a shifting in the proportion of ECW in TBW.
      Clinical and pharmacological treatments based upon past assumptions of body water
      volumes, proportions and relationships could produce inaccurate estimates.

PMID- 17435954
TI  - The potential influence of silica present in drinking water on Alzheimer's
      disease and associated disorders.
AB  - Silica present in drinking water may be protective with respect to the decrease
      of cognitive function as it was suggested by several epidemiologic studies. Data
      from French cohort have demonstrated that aluminium in drinking water seems to
      have a deleterious effect and increased the risk of cognitive impairment when the
      silica concentrations were low. Moreover, it has been shown that the performances
      to a cognitive test were positively correlated to the consumption of silica and
      that the risk of Alzheimer's disease (AD) was reduced in subjects who had the
      higher daily silica intake compared to the others. The silica is probably the
      natural antidote of the aluminium and could play a benefit role by decreasing the
      biodisponibility of aluminium, whose neurotoxicity is now clearly established.
      Data have suggested the possible use of silicates as a therapeutic agent for AD
      since both model tangles and precipitated beta-pleated sheets of betaA4 can be
      reversed to soluble forms by silicates. The role of silica in drinking water on
      cognitive function has been however little studied and clear results have not yet
      emerge. The potential benefit of silica needs to be confirmed in additional
      investigations to exclude causes of error related to certain methodological
      biases. If such association do indeed exist, interventional strategies could be
      set up to reduce the incidence of AD. The aim of this paper is to review articles
      published on silica present in drinking water in relation with AD and associated
      disorders.

PMID- 17435955
TI  - The New Mexico aging process study (1979-2003). A longitudinal study of
      nutrition, health and aging.
AB  - In 1979, Dr. James S. Goodwin, M.D., assisted by Philip J. Garry, Ph.D.,
      submitted a grant proposal to the United States Public Health Service/ National
      Institute on Aging (NIA) entitled, "A prospective study of nutrition in the
      elderly". This study was approved and funded by the NIA beginning in 1979.
      Initially, approximately 300 men and women over 65 years of age with no known
      medical illnesses and no prescription medications were selected for this study.
      The primary purpose of this multi disciplinary study, known in the literature as
      the New Mexico Aging Process Study (NMAPS), was to examine the role of nutrition
      and resultant changes in body composition and organ function in relation to the
      aging process and health status of the elderly. This was accomplished by
      following prospectively healthy elderly volunteers, obtaining in-depth
      information about dietary habits, lifestyle, body composition, organ function,
      cognitive status, vitamin metabolism, genetic markers, and biochemical measures
      of nutritional status and then examining these data in relationship to age and
      health status and changes in health status. Some of the specific aims of the
      study were modified over the course of this longitudinal study because of
      availability of University of New Mexico School of Medicine faculty with
      expertise in different areas of aging research. In 1988, Dr. Bruno Vellas from
      the University Hospital in Toulouse, France became an on-going visiting professor
      at the University of New Mexico School of Medicine. From 1988, until the study
      was terminated in 2003, Dr. Vellas has collaborated with the faculty involved in
      the NMAPS on a number of research projects. In this article, we provide
      information about the studies overall design and briefly describe some of the
      major finding of the NMAPS.

PMID- 17435952
TI  - Silicon and bone health.
AB  - Low bone mass (osteoporosis) is a silent epidemic of the 21st century, which
      presently in the UK results in over 200,000 fractures annually at a cost of over
      one billion pounds. Figures are set to increase worldwide. Understanding the
      factors which affect bone metabolism is thus of primary importance in order to
      establish preventative measures or treatments for this condition. Nutrition is an
      important determinant of bone health, but the effects of the individual nutrients
      and minerals, other than calcium, is little understood. Accumulating evidence
      over the last 30 years strongly suggest that dietary silicon is beneficial to
      bone and connective tissue health and we recently reported strong positive
      associations between dietary Si intake and bone mineral density in US and UK
      cohorts. The exact biological role(s) of silicon in bone health is still not
      clear, although a number of possible mechanisms have been suggested, including
      the synthesis of collagen and/or its stabilization, and matrix mineralization.
      This review gives an overview of this naturally occurring dietary element, its
      metabolism and the evidence of its potential role in bone health.

PMID- 17435956
TI  - IANA task force on nutrition and cognitive decline with aging.
AB  - Cognitive impairment can be influenced by a number of factors. The potential
      effect of nutrition has become a topic of increasing scientific and public
      interest. In particular, there are arguments that nutrients (food and/or
      supplements) such as vitamins, trace minerals, lipids, can affect the risk of
      cognitive decline and dementia, especially in frail elderly people at risk of
      deficiencies. Our objective in this paper is to review data relating diet to risk
      of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose
      to focus our statements on homocysteine-related vitamins (B-vitamins),
      antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic
      cofactors) and dietary lipids. Results of epidemiological studies may sometimes
      appeared conflicting; however, certain associations are frequently found. High
      intake of saturated and trans-unsaturated (hydrogenated) fats were positively
      associated with increased risk of AD, whereas intake of polyunsaturated and
      monounsaturated fats were protective against cognitive decline in the elderly in
      prospective studies. Fish consumption has been associated with lower risk of AD
      in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective
      role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and
      dementia. Finally, the results on antioxidant nutrients may suggest the
      importance of having a balanced combination of several antioxidant nutrients to
      exert a significant effect on the prevention of cognitive decline and dementia,
      while taking into account the potential adverse effects of these nutrients. There
      is no lack of attractive hypotheses to support research on the relationships
      between nutrition and cognitive decline. It is important to stress the need to
      develop further prospective studies of sufficiently long duration, including
      subjects whose diet is monitored at a sufficiently early stage or at least before
      disease or cognitive decline exist. Meta analyses should be developed, and on the
      basis of their results the most appropriate interventional studies can be
      planned. These studies must control for the greatest number of known confounding
      factors and take into account the impact of the standard social determinants of
      food habits, such as the regional cultures, social status, and educational level.

PMID- 17435957
TI  - The effects of soy milk and isoflavone supplements on cognitive performance in
      healthy, postmenopausal women.
AB  - RATIONALE: The decline in estrogen concentrations in women after menopause can
      contribute to health related changes including impairments in cognition,
      especially memory. Because of the health concerns related to hormone replacement
      therapy (HRT), alternative approaches to treat menopausal symptoms, such as
      nutritional supplements and/or diet containing isoflavones, are of interest.
      OBJECTIVES: This study investigated whether soy isoflavones (soy milk and
      supplement) could improve cognitive functioning in healthy, postmenopausal women.
      PARTICIPANTS, INTERVENTION AND DESIGN: A total of 79 postmenopausal women, 48-65
      years of age, completed a double-blind, placebo-controlled trial in which they
      were randomly assigned to one of three experimental groups: cow's milk and a
      placebo supplement (control); soy milk and placebo supplement (soy milk, 72 mg
      isoflavones/day); or cow's milk and isoflavone supplement (isoflavone supplement,
      70 mg isoflavones/day). MEASUREMENTS: Cognitive functioning was assessed using
      various cognitive tasks before the intervention (baseline) and after the
      intervention (test). RESULTS: In contrast to predictions, soy isoflavones did not
      improve selective attention (Stroop task), visual long-term memory (pattern
      recognition), short-term visuospatial memory (Benton Visual Retention Test), or
      visuo-spatial working memory (color match task). Also, the soy milk group showed
      a decline in verbal working memory (Digit Ordering Task) compared to the soy
      supplement and control groups. CONCLUSION: Soy isoflavones consumed as a food or
      supplement over a 16-week period did not improve or appreciably affect cognitive
      functioning in healthy, postmenopausal women.

PMID- 17435958
TI  - Descriptive data on lifestyle, anthropometric status and mental health in italian
      elderly people.
AB  - OBJECTIVE: The objective of this paper is to provide descriptive information on
      anthropometric status, pathological conditions, cognitive impairment and
      lifestyle in apparently healthy elderly Italian people. DESIGN, SETTING AND
      SUBJECTS: In order to recruit the volunteers for the ZENITH study, 359 Italian
      participants (167 men and 192 women), aged between 70 and 85 years, free living
      in Rome, were selected. Volunteers underwent a full clinical examination,
      anthropometric measurements (height, weight), a lifestyle questionnaire and
      mental health assessment (cognitive impairment and depression). RESULTS: The
      prevalence of overweight and obesity was high (57% and 22% in men; 43% and 27% in
      women). Obesity was associated with low socio-economic profile in about 40% of
      participants. Although the sample was selected by family doctors and was
      apparently healthy, after medical screening the presence of several pathologies,
      particularly diabetes in 21% of participants was observed. There was a low
      prevalence of cognitive impairment in 4% of men and 7% of women and possible
      depression in 9% of men and 19% of women. The lifestyle questionnaire showed that
      most of their time was spent in light activities such as reading, watching TV or
      playing cards and significant differences between sex and BMI categories were
      observed (P=0.000). CONCLUSION: The results confirm the increasingly sedentary
      lifestyle of modern populations and demonstrate the need for sensitive and
      individualised strategies to design appropriate health promotion and disease
      prevention programs for older adults.

PMID- 17435959
TI  - Calcium and vitamin d reduces falls and fractures--confusion and controversy.

PMID- 17435960
TI  - Association of resident, facility, and geographic characteristics with chronic
      undernutrition in a nationally represented sample of older residents in U.S.
      nursing homes.
AB  - BACKGROUND: Undernutrition (also known as protein-calorie malnutrition or energy
      deficiency) is associated with exacerbation of health conditions, increased
      frailty, and decline in physical, cognitive, and affective function. This is a
      critical problem for older adults who reside in nursing homes and have many
      limitations that contribute to reduced food intake. OBJECTIVE: To determine the
      relationship of chronic undernutrition [body mass index (BMI) < 18.5 kg/m2] to
      resident, facility, and geographical characteristics in a national sample of
      nursing home residents aged 60 y or older in the U.S. DESIGN: A cross-sectional,
      secondary analysis of a 10% nationally representative random sample of annual
      assessments of nursing home residents in the U.S. (n = 128,514), using the
      Minimum Data Set (MDS). Data included measured weight and height, resident
      characteristics, facility characteristics, and geographic location. RESULTS: More
      than 12% (n = 15,566) were chronically undernourished (energy-deficient), with
      more than 27% of those being severely undernourished (BMI < 16). Independent
      correlates of chronic undernutrition (multivariate analysis) included resident
      characteristics (ADL, having chewing or swallowing problems, or leaving at least
      25% of the meal uneaten), facility characteristics (% Medicare and for-profit
      status), and geographic characteristics (living in nursing home in urban or large
      towns). CONCLUSION: This study found a high percentage of chronic undernutrition
      in this nationally representative sample of U.S. nursing home residents.
      Furthermore, resident, facility, and geographic characteristics were associated
      with chronic undernutrition. Strategies need to be developed and documented that
      ensure nutritional health to residents with a variety of health problems.

PMID- 17435961
TI  - Effect of creatine supplementation during resistance training on muscle accretion
      in the elderly.
AB  - Sarcopenia, defined as the age-related loss of muscle mass, is a serious health
      concern. Contributing factors to sarcopenia include physical inactivity and
      undernutrition. Resistance training has a positive effect on muscle mass in the
      elderly. However, muscle loss is still observed in older adults who perform
      weight bearing exercise; suggesting that nutrition is important. Creatine
      supplementation has the potential to increase muscle accretion during resistance
      training, although the mechanism for its ergogenic effect is unclear. Creatine
      has the potential to increase cellular hydration and myogenic transcription
      factors and facilitate the up-regulation of muscle specific-genes such as myosin
      heavy chain possibly leading to muscle hypertrophy.

PMID- 17435962
TI  - Influence of water quality on cholesterol induced systemic pathology.
AB  - Reduced systemic pathology was identified in cholesterol-fed rabbits administered
      distilled water compared to animals drinking local tap water; this included
      pathology of the liver and spleen. Studies directed at determining the effect of
      the trace metals aluminum, copper and zinc on cholesterol-induced systemic
      pathology were undertaken. As previously reported copper added to distilled
      drinking water (0.12 PPM) increased Alzheimer-like pathology in the brain, but
      did not augment pathology of the spleen or liver. Aluminum added to distilled
      water (0.36 PPM) administered to drink exacerbated cholesterol-induced hepatic
      pathology but not splenic pathology, and addition of 0.36 PPM zinc to the
      distilled drinking water failed to affect pathology of either the liver or
      spleen. The overall increase in both central and systemic pathology observed
      among cholesterol-fed rabbits administered tap water seems to be due to different
      trace metal contaminants occurring in tap water.

PMID- 17435963
TI  - Anorexia of aging in long term care: is dronabinol an effective appetite
      stimulant?--a pilot study.
AB  - INTRODUCTION: Anorexia and subsequent weight loss increase the risk of death in
      long term care (LTC) residents. In patients who fail to respond to nutritional
      intervention, orexigenic drugs are sometimes prescribed. There is limited data
      regarding the safety and efficacy of these drugs in older adults. OBJECTIVE: To
      examine the effect of a 12-week course of dronabinol on LTC residents with
      anorexia and significant weight loss. DESIGN, SETTING, PARTICIPANTS:
      Retrospective observational study on residents in five LTC facilities in a major
      metropolitan area. RESULTS: Twenty-eight subjects (22F, 6M) were involved in the
      study. Mean age 79.5 +/- 19.8 years (range 46-98 y). Mean body weight, serum
      albumin and serum prealbumin at baseline were 105.7 +/- 24.7 lbs, 3.39 +/- 0.47
      g/dl and 22.15 +/- 7.92 mg/dl respectively. 15 subjects (53.5%) gained weight on
      dronabinol, of which 10 (67%) gained more than 5 lbs and 6(40%) gained more than
      10 lbs. Five (33%) subjects gained less than 5 lbs. Residents who lost weight on
      dronabinol were younger than those who gained weight (70.9 +/- 5.62 y and 90.8 +/
      7.84 y respectively; p = 0.007) Overall, the mean weight gain on dronabinol was
      3 +/- 8.01 lbs (p=0.2). Eleven subjects lost weight (mean loss 3 +/- 2.6 lbs). Of
      the subjects who lost weight 7 (64%) died compared with 4 (26%) in the subgroup
      who gained weight. CONCLUSIONS: Dronabinol therapy was well tolerated. Overall,
      there was a trend toward weight gain in LTC residents treated with 12 weeks of
      dronabinol. Failure to respond to dronabinol may indicate increased risk of
      death.

PMID- 17435964
TI  - Evaluation of alachlor herbicide impacts on Nile tilapia (Oreochromis niloticus)
      using biochemical biomarkers.

PMID- 17435965
TI  - Does bladder neck descent increase with age?
AB  - It is assumed that pelvic organ descent and prolapse increase with age.
      Epidemiological studies support this assumption. We aimed to define the
      relationship between age and bladder neck descent (BND) in a retrospective
      observational study on 790 women referred for evaluation of pelvic floor
      disorders. Bladder neck descent, cystocele descent and urethral rotation were
      evaluated on maximal Valsalva manoeuvre, using trans-labial ultrasound. There was
      a weak negative correlation between bladder neck descent on Valsalva and age (r =
      -0.154, p < 0.001), which was absent in nulliparous women (n = 107) and stronger
      (r = -0.213, p < 0.001) in parous women (n = 683). This relationship was evident
      from the age of 50 years onwards and may be explained by increased tissue
      stiffness after menopause. The difference observed between parous and nulliparous
      women is intriguing and raises the issue of obstetric confounders such as
      historical changes in the likelihood of significant pelvic floor trauma.

PMID- 17435966
TI  - Communicative contexts of the LEN facial expression of pigtailed macaques (Macaca
      nemestrina).
AB  - We have investigated the contexts of the LEN (lips forward-ears back-neck
      extended) or pucker, a species-specific facial expression of Macaca nemestrina,
      in four breeding groups. Using the behavior sampling method we recorded all LENs,
      associated behavior, and the identities of the individuals involved. Of 401 LENs
      initiated, 62% were directed to the observer, who never responded to them in any
      way. Infants and dams directed more LENs to the observer than did sires or other
      females. The average intraspecific LEN rate was 0.82 per monkey-hour, including
      LENs given in reciprocation. Excluding LENs given in reciprocation, sires LENned
      significantly more often to females and dams than to infants, and significantly
      more than females and dams LENned to them. Of LENs directed to conspecifics, 21%
      were reciprocated, 34% were followed by distance reduction, and 16% led to both.
      Reciprocating LEN responses occurred more often to LENs initiated by sires.
      Although primarily affiliative, some LENs occurred in agonistic contexts,
      suggesting a possible appeasing function or rejection of a LEN's social
      invitation. Aggression preceded 8% of conspecific LENs, and 15% of LENs were
      responded to by visual aggression. No response followed 47% of LENs. Affirming
      the conclusions of others, LENs are often directed by males to females before
      mating. LENs directed at cradled infants suggest that maternal LENs serve more
      than a summoning function. LENs directed to people by M. nemestrina usually seem
      to be inviting interaction or attention, but LENs by dams seem to reflect
      concerns over their infants. We speculate that at the most basic level the LEN
      emphasizes that the sender's gaze is fixed on the receiver. We propose that the
      LEN may have evolved in this quiet rainforest species to facilitate coordination
      of social activity when silence or stealth is advantageous.

PMID- 17435967
TI  - ISCEV standard for clinical pattern electroretinography--2007 update.
AB  - The pattern electroretinogram (PERG) is a retinal response evoked by viewing a
      temporally alternating pattern, usually a black and white checkerboard or
      grating. The PERG is important in clinical and research applications because it
      provides information both about retinal ganglion cell function and, because the
      stimulus is customarily viewed with central fixation, the function of the macula.
      The PERG can therefore facilitate interpretation of an abnormal pattern VEP by
      revealing the retinal responses to a similar stimulus to that used for the VEP.
      However, practitioners may have difficulty choosing between the different
      techniques for recording the PERG that have been described in the literature. The
      International Society for Clinical Electrophysiology of Vision published a
      standard for clinical PERG recording in 2000 to assist practitioners in obtaining
      good quality reliable responses and to facilitate inter-laboratory communication
      and comparison. This document is the scheduled revision of that standard.

PMID- 17435968
TI  - Prognostic factors in Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To identify prognostic factors for final visual outcome, development of
      complications, and recurrent inflammation in patients with Vogt-Koyanagi-Harada
      (VKH) disease. METHODS: All patients diagnosed with acute uveitis associated with
      VKH disease at the King Khaled Eye Specialist Hospital and King Abdulaziz
      University Hospital between January 1999 and February 2004 were reviewed. Data
      collected included age, gender, initial and final visual acuities, clinical
      findings at presentation, interval between onset of disease and starting
      treatment, treatment received, complications, number of recurrences, extraocular
      manifestations, and duration of follow-up period. RESULTS: Sixty-eight patients
      were identified. There were 51 (75%) females and 17 (25%) males with a mean age
      of 25.04 +/- 10.28 years (range 7-55 years). The mean follow-up period was 34.4
      +/- 20.1 months (range 8-62 months). The following factors were significantly
      associated with final visual acuity of 20/20 by univariate analysis: good initial
      visual acuity of better than 20/200 (p = 0.0415), absence of posterior synechiae
      of the iris at presentation (p = 0.0106), use of systemic corticosteroids for
      longer than nine months (p = 0.0479), slow tapering of systemic corticosteroids
      (p = 0.0024), absence of complications (p < 0.001), and absence of extraocular
      manifestations (p = 0.0124). Logistic regression analysis identified the use of
      systemic corticosteroids for longer than nine months to be associated with final
      visual acuity of 20/20 [odds ratio = 3.4; 95% confidence interval (CI) = 1.14
      10.1]. The following factors were significantly associated with the development
      of complications by univariate analysis: age older than 18 years (p = 0.0161),
      initial visual acuity of 20/200 or worse (p = 0.0011), and presence of posterior
      synechiae of the iris at presentation (p = 0.0453). Factors identified after
      logistic regression analyses were age older than 18 years (odds ratio = 3.3; 95%
      CI = 1.33-8.17), and presence of posterior synechiae of the iris at presentation
      (odds ratio = 3.42; 9% CI = 1.38-8.47). Initial visual acuity of better than
      20/200 was significantly associated with a lower risk of developing complications
      (odds ratio = 0.283; 95% CI = 0.129-0.629). The following factors were
      significantly associated with recurrent inflammation of three times or more by
      univariate analysis: initial visual acuity of 20/200 or worse (p = 0.0179),
      anterior chamber reaction of more than 2+ at presentation (p < 0.001), rapid
      tapering of systemic corticosteroids (p < 0.001), and development of extraocular
      manifestations (p = 0.0277). CONCLUSIONS: Clinical findings at presentation,
      duration and method of tapering of systemic corticosteroids, and development of
      extraocular manifestations are significantly associated with final visual acuity,
      development of ocular complications, and recurrent inflammation. The development
      of ocular complications was significantly associated with a worse final visual
      acuity.

PMID- 17435969
TI  - Pathology of Vogt-Koyanagi-Harada disease.
AB  - Typical histopathologic features of Vogt-Koyanagi-Harada disease (VKH) include
      granulomatous panuveitis with preservation of the choriocapillaris and exudative
      retinal detachment. In the chronic stage of the disease, however, histologic
      changes consist of nongranulomatous uveitis followed, in the chronic recurrent
      stage, by granulomatous uveitis and involvement of the choriocapillaris. In
      chronic VKH the peripheral fundus scars are not Dalen-Fuchs nodules; they are,
      instead, indicative of focal chorioretinal atrophy with loss of retinal pigment
      epithelium.

PMID- 17435970
TI  - Biodegradable poly(2-dimethylamino ethylamino)phosphazene for in vivo gene
      delivery to tumor cells. Effect of polymer molecular weight.
AB  - PURPOSE: Previously, we have shown that complexes of plasmid DNA with the
      biodegradable polymer poly(2-dimethylamino ethylamino)phosphazene (p(DMAEA)-ppz)
      mediated tumor selective gene expression after intravenous administration in
      mice. In this study, we investigated the effect of p(DMAEA)-ppz molecular weight
      on both in vitro and in vivo tumor transfection, as well as on complex induced
      toxicity. MATERIALS AND METHODS: p(DMAEA)-ppz with a broad molar mass
      distribution was fractionated by preparative size exclusion chromatography.
      Polyplexes consisting of plasmid DNA and the collected polymer fractions were
      tested for biophysical properties, (cyto)toxicity and transfection activity.
      RESULTS: Four p(DMAEA)-ppz fractions were collected with weight average molecular
      weights ranging from 130 to 950 kDa, and with narrow molecular mass distributions
      (Mw/Mn from 1.1 to 1.3). At polymer-to-DNA (N/P) ratios above 6, polyplexes based
      on these polymers were all positively charged (zeta potential 25-29 mV), and had
      a size of 80-90 nm. The in vitro cytotoxicity of the polyplexes positively
      correlated with polymer molecular weight. The in vitro transfection activity of
      the different polyplexes depended on their N/P ratio, and was affected by the
      degree of cytotoxicity, as well as the colloidal stability of the different
      polyplexes. Intravenous administration of polyplexes based on the high molecular
      weight polymers led to apparent toxicity, as a result of polyplex-induced
      erythrocyte aggregation. On the other hand, administration of polyplexes based on
      low molecular weight p(DMAEA)-ppz's (Mw 130 kDa) did not show signs of toxicity
      and resulted in tumor selective gene expression. CONCLUSION: Polymer molecular
      weight fractionation enabled us to optimize the transfection efficiency/toxicity
      ratio of p(DMAEA)-ppz polyplexes for in vitro and in vivo tumor transfection.

PMID- 17435971
TI  - Endogenous expression of angiogenesis-related factors in response to muscle
      injury.
AB  - Gene therapy has developed a new strategy to treat a variety of ischemic diseases
      using angiogenic growth factors. However, the endogenous expression pattern of
      angiogenesis-related factors in response to muscle injury is not fully
      characterized. In the present study, we investigated the expression of
      angiogenesis-related factors, vascular endothelial growth factor, angiopoietin-1,
      -2, monocyte chemoattractant protein-1, and their receptors during muscle
      regeneration. Mice underwent freeze injury, and then the gastrocnemius muscles
      were isolated 1, 3, 5, 7, 10, 14, and 28 days after surgery. Generally, changes
      in gene expression were most dramatic during the early stage of muscle
      regeneration, and were attenuated as angiogenesis progressively developed and
      then returned to steady-state levels. VEGF mRNA began to increase from day 3 and
      peaked at day 5 after muscle injury. VEGF receptors, Flt-1, KDR/Flk-1, and
      neuropilin-1 mRNAs were increased from 3- to 9-fold at day 3 after muscle injury.
      At the same time, angiopoietin-1 and angiopoietin-2 mRNA were increased by 3- and
      15-fold respectively, concomitantly with an increase in their receptors and Tie-2
      mRNA. Finally, MCP-1 and CC-chemokine receptor 2 mRNAs were sharply up-regulated
      by 1600- and 100-fold, respectively, at day 3 after muscle injury. These results
      suggest that the molecular events implicated in angiogenesis occur at an early
      stage of muscle regeneration.

PMID- 17435976
TI  - [Preoperative administration of angiotensin-converting enzyme inhibitors].
AB  - INTRODUCTION: The discussion about perioperative withdrawal or continuation of
      angiotensin-converting enzyme inhibitors (ACEI) remains controversial. Should it
      be continued to avoid peaks in blood pressure and heart rate during anesthesia?
      Or should it be discontinued the day before to avoid clinically relevant
      hypotonia? What is the greater risk? Since there are only a few studies dealing
      with this question, we compared the cardio-circulatory reaction during anesthesia
      after withdrawal and with continuation of ACEI therapy. METHODS: A total of 100
      hypertonic patients chronically treated with ACEIs were included in this
      prospective, randomized, double blind study. The last ACEI medication was given
      with the premedication in the morning (premed) or on the day before (withdrawal).
      Blood pressure and heart rate during induction and termination of anesthesia were
      compared between both groups. A threshold value for vasopressor therapy was
      determined to be a mean arterial pressure of 60 mmHg. RESULTS: In the premed
      group Akrinor was necessary significantly more often and in higher dosages.
      Nevertheless, following induction the blood pressure and heart rates were
      significantly lower compared to the withdrawal group. The highest blood pressure
      and heart rate during induction and termination of anesthesia did not differ
      between the groups. CONCLUSIONS: The continuation of ACEI therapy in the morning
      is not associated with a better control of blood pressure and heart rate but
      causes a more pronounced hypotension which forced a therapy more often. Patients
      chronically treated with ACEI should receive the ACEI the last time on the day
      before the operation and not with the premedication in the morning.

PMID- 17435977
TI  - [Anaesthesiology as a compulsory subject in the new German medical school
      curriculum. Evaluation of a curricular model at the University Hospital Aachen].
AB  - BACKGROUND: Since October 2003 new regulations for qualifications to practice
      medicine in Germany now require compulsory courses in anaesthesiology. Therefore,
      existing curricular activities had to be changed from facultative courses for a
      small number of interested students to compulsory activities for all students.
      METHODS: Previous data of the department of anaesthesiology at the University
      Hospital Aachen (Germany) were collected and taken into consideration for the
      development of a new curriculum: The result was a course consisting of a tutorial
      with integrated "basic skill training", practical training in the operating
      theatre and a simulation-based session, in addition to two series of lectures. An
      evaluation by the students was carried out using EvaLuna as a tool for web-based
      on-line evaluation and faculty members had to fill out a standardized
      questionnaire. RESULTS: The different parts of the curriculum received the
      highest scores of all courses in the undergraduate medical school curriculum.
      Best results were achieved by the anaesthesia-simulation session followed by the
      tutorial and the practical training. CONCLUSION: The feedback of faculty members
      as well as the results of students' evaluation approved the developed concept of
      integrating anaesthesia-relevant issues into the formal medical school
      curriculum. Nevertheless, the on-line evaluation system EvaLuna provided
      additional suggestions for future improvements in the newly created curriculum.

PMID- 17435978
TI  - [Covering palmar thumb tip defects with the Littler-Flap].

PMID- 17435979
TI  - Arterial variants in pancreatic adenocarcinoma.
AB  - Surgery remains the only curative option for the treatment of pancreatic
      adenocarcinoma. Local tumor resectability depends on a number of factors, but
      most importantly, the relationship of the tumor to adjacent arterial structures.
      For example, surgery is rarely performed when the tumor involves the celiac axis
      or the superior mesenteric artery. Unexpected variant arterial anatomy or tumor
      involvement of aberrant arteries may complicate pancreatic surgery. The classic
      visceral arterial anatomy occurs in only 55%-60% of the population, with one or
      more variant vessels occurring in the remaining population. Knowledge of both
      variant and normal anatomy is essential for accurate preoperative planning. We
      describe here the arterial variant anatomy of the pancreas and its identification
      by multidetector CT imaging, with and without the aid of post-processed volume
      rendered images.

PMID- 17435980
TI  - Diffusion-weighted MR imaging of hepatic abscesses: possibility of different
      apparent diffusion coefficient (ADC)-values in early and mature abscess
      formation.

PMID- 17435981
TI  - The choledochal ring sign: a specific finding in acute biliary pancreatitis.
AB  - We investigated a marked common bile duct wall contrast-enhancement in acute
      pancreatitis on CT scans as an accurate sign of biliary pancreatitis. Contrast
      enhanced CT scans of 80 patients with clinically and biologically confirmed acute
      pancreatitis were reviewed by two gastrointestinal radiologists without knowledge
      of the cause of acute pancreatitis. Since this study was retrospective and then
      did not modify the CT examination routinely performed in acute abdomen, no
      institutional review board approval and informed consent was requested. A
      systematic measure of the difference between the CT number of common bile duct
      wall and the CT number of pancreatic parenchyma was performed. The "choledochal
      ring" sign, defined by a difference greater than 15 HU was specifically studied
      and compared to other factors often associated with biliary pancreatitis through
      univariate and multivariate analyses. Compared to other factors classically
      associated with acute biliary pancreatitis, the "choledochal ring" sign showed
      high specificity (100%) and high positive predictive value (100%). In patients
      with acute pancreatitis, the "choledochal ring" sign is a new and accurate
      finding of acute biliary pancreatitis on CT scans.

PMID- 17435982
TI  - Small bowel infarcts in Degos disease.
AB  - Degos disease is a rare idiopathic vasculopathy with multisystem involvement. We
      present a previously healthy 40-year-old woman who developed spontaneous small
      bowel infarctions and perforations 17 months after presentation with
      characteristic skin lesions. The abdominal CT findings of Degos disease, which
      have not been previously depicted in the radiology literature, are discussed.

PMID- 17435983
TI  - Severity prediction in acute pancreatitis: the role of early CT scan.

PMID- 17435984
TI  - Imaging features of postpartum uterine rupture: a case report.
AB  - We present a case report on a postpartum uterine rupture with the history of a
      previous cesarean section. During the diagnosis of rupture, ultrasound,
      computerized tomography (CT) and magnetic resonance imaging of the uterus were
      obtained. Ultrasound examination did not result in substantial information. CT
      and magnetic resonance imaging established the correct diagnosis. The patient
      underwent exploratory laparotomy, and the diagnosis was confirmed. Diagnostic
      qualifications of these three instruments were compared.

PMID- 17435985
TI  - Feeding selectivity by mantled howler monkeys (Alouatta palliata) in relation to
      leaf secondary chemistry in Hymenaea courbaril.
AB  - This study is a quantitative examination of primate feeding selectivity in
      relation to secondary chemistry within a single plant species, Hymenaea
      courbaril. It provides the first evidence that sesquiterpenes may act as feeding
      deterrents in mantled howler monkeys. A free-ranging group of mantled howler
      monkeys at the study site of Sector Santa Rosa, Area de Conservacion Guanacaste,
      Costa Rica were observed for the 2-month period of H. courbaril leaf flush in
      1999. Tree characteristic data and leaf specimens were collected from 22 focal
      trees. Gas chromatography and mass spectrometry were used to estimate relative
      percentages of sesquiterpenes in leaf specimens. The monkeys fed only on the
      youngest leaves and only from particular trees. Whereas leaf stage selectivity
      was likely governed by tannin content and structural carbohydrates in younger and
      older leaf stages, respectively, differential tree use may be related to
      variability in sesquiterpene content. There is evidence that alpha-copaene may
      have played a role in interindividual tree use, and that cyperene may also be
      implicated. However, there is no reported evidence of antiherbivore activity for
      cyperene.

PMID- 17435986
TI  - Perception of conspecific female pheromone stimulates female calling in an
      arctiid moth, Utetheisa ornatrix.
AB  - Perception of the female sex pheromone in Utetheisa ornatrix (Lepidoptera:
      Arctiidae) is responsible for induction and adjustment of calling by females and
      the collective phenomenon termed "female pheromonal chorusing". We found five
      olfactory-active compounds in the U. ornatrix female gland. When females were
      exposed to the entire pheromone or to two of its (synthetically prepared)
      components, (Z,Z,Z)-3,6,9-eicosatriene and (Z,Z,Z)-3,6,9-heneicosatriene, they
      were more likely to call during a given night, begin calling earlier, and briefly
      increase signal frequency with which they extrude their abdomen, an observable
      indication of calling in this species. Some females even initiated calling during
      photophase when exposed to the pheromone components. In general, female U.
      ornatrix are more sensitive to the complete blend of pheromone than to its
      individual compounds. We also tested the hypotheses: 1) that abdominal extrusion
      per se increases the rate of pheromone release; and 2) that greater abdominal
      pumping rhythm increases pheromone release rate. Contrary to our expectations: 1)
      females did not respond more strongly to a pulsed pheromone stimulus than to the
      constant release of pheromone at the same average release rate; and 2) we did not
      find a relationship between the frequency of abdominal pumping and pheromone
      release rate. Possible explanations for these unexpected findings are discussed.

PMID- 17435987
TI  - [Thrombolysis for ischemic stroke: an update].
AB  - Even 10 years after the approval of thrombolysis this life-saving and disability
      reducing therapy is still underused. Important reasons for that are very strict
      inclusion criteria such as the early and narrow time-window, fear of bleeding
      complications and doubts regarding the effectiveness. An intensive and constant
      effort is required to educate the public that stroke is a treatable emergency. In
      addition to the medical reasons, economic considerations in a context of
      decreasing resources emphasize the importance of effective stroke treatment. The
      results of numerous recent studies such as the European register SITS-MOST help
      to strengthen the confidence in thrombolysis. In addition the development and
      advancement of new imaging tools such as multiparametric MRI and advanced CT
      techniques will improve patient selection and may enable us to extend the time
      window for treatment. Intraarterial thrombolysis, "bridging" methods and new
      devices for intravascular intervention are the subjects of intensive ongoing
      research. Even though no randomized trials are available intraarterial
      thrombolysis is the treatment of choice for acute basilar occlusion, but if this
      intervention is not available an intravenous approach may be an equal
      alternative.

PMID- 17435989
TI  - [Penile injury caused by a Moulinette. Result of autoerotic self-mutilation].
AB  - Autoerotic manipulations of external male genitals resulting in mutilation with
      different degrees of severity are rare. We report the clinical case of a 12-year
      old boy who injured his glans, left corpus cavernosum and corpus spongiosum with
      opened urethra as a consequence of autoerotic genital self-mutilation. According
      to our knowledge of the current literature this is the first description of
      autoerotic genital self-mutilation with a Moulinette. A Moulinette is a kitchen
      tool with an electric engine and an extremely fast rotary double knife, which is
      used to reduce food into small pieces, especially vegetables and fruits.

PMID- 17435990
TI  - [Radical and partial nephrectomy for RCC: laparoscopy or open surgery].
AB  - After initial scepticism laparoscopic radical nephrectomy has rapidly been
      developed to a standard of care which should be offered to all patients as an
      alternative to open surgery. This procedure is indicated for all renal tumours
      clinical stage 1-2 which are not considered for partial nephrectomy. Many studies
      now show that the oncologic outcome is good and comparable to open surgery.
      Follow-up, however, is limited to about 10 years. Laparoscopic radical
      nephrectomy has become a standardized procedure. Removal of the kidney by
      morcellation, favoured by the majority some time ago, has been abandoned to a
      great extent. Also the controversy about the advantages and disadvantages of the
      respective approach has been settled. Several prospective randomized studies
      proved that both the transperitoneal and retroperitoneal approaches are equally
      effective. Excluding the bias of the learning curve the complication rate of
      laparoscopy is not higher than that of open surgery, but morbidity is clearly
      lower. Since the rate of elective partial nephrectomy is increasing rapidly,
      laparoscopy may be a good choice for this indication as well. When performed
      during ischaemia all principles of open surgery--excision of the tumour with
      clear margins, haemostasis using sutures, closure of the collecting system,
      suture repair of the renal parenchyma--can be duplicated. The problem of long
      warm ischaemia time can be managed by the evolution of the surgical technique,
      but also by induction of hypothermia. Complication rates are comparable to open
      surgery. Oncologic results, with limited follow-up however, are promising.

PMID- 17435991
TI  - Case involving end-of-life decision issues in Italy.

PMID- 17435993
TI  - CdS quantum dots as fluorescence probes for the sensitive and selective detection
      of highly reactive HSe- ions in aqueous solution.
AB  - Water-soluble cadmium sulfide (CdS) quantum dots (QDs) capped by mercaptoacetic
      acid were synthesized by aqueous-phase arrested precipitation, and characterized
      by transmission electron microscopy, spectrofluorometry, and UV-Vis
      spectrophotometry. The prepared luminescent water-soluble CdS QDs were evaluated
      as fluorescence probes for the detection of highly reactive hydrogen selenide
      ions (HSe(-) ions). The quenching of the fluorescence emission of CdS QDs with
      the addition of HSe(-) ions is due to the elimination of the S(2-) vacancies
      which are luminescence centers. Quantitative analysis based on chemical
      interaction between HSe(-) ions and the surface of CdS QDs is very simple, easy
      to develop, and has demonstrated very high sensitivity and selectivity features.
      The effect of foreign ions (common anions and biologically relevant cations) on
      the fluorescence of the CdS QDs was examined to evaluate the selectivity. Only
      Cu(2+) and S(2-) ions exhibit significant effects on the fluorescence of CdS QDs.
      With the developed method, we are able to determine the concentration of HSe(-)
      ions in the range from 0.10 to 4.80 micromol L(-1), and the limit of detection is
      0.087 micromol L(-1). The proposed method was successfully applied to monitor the
      obtained HSe(-) ions from the reaction of glutathione with selenite. To the best
      of our knowledge, this is the first report on fluorescence analysis of HSe(-)
      ions in aqueous solution.

PMID- 17435992
TI  - Tandem regulation of phosphoinositide signaling and acute behavioral effects
      induced by antidepressant agents in rats.
AB  - RATIONALE: Antidepressants increase synaptic monoamine concentrations, but the
      subsequent signaling events that produce the beneficial clinical effects remain
      unclear. Diverse antidepressants increase CDP-diacylglycerol, a crucial step in
      phosphoinositide signaling. Serotonin 5HT(2) receptors, implicated in depression
      or the actions of some antidepressants, signal through phosphoinositide
      hydrolysis. Thus, cross talk between antidepressant-induced CDP-diacylglycerol
      and 5HT(2) signaling could contribute to the antidepressant mechanism. OBJECTIVE:
      The objective of the study was to test the hypotheses that antidepressants
      enhance net signaling via 5HT(2) receptors by augmenting the supply of
      phosphoinositide substrates and that this action contributes to the behavioral
      effects of the drugs. MATERIALS AND METHODS: Brain slices pre-labeled with
      [(3)H]inositol in the presence of various antidepressant concentrations were
      washed and incubated with the 5HT(2) agonist, alpha-methylserotonin, followed by
      measuring phosphoinositide synthesis and inositol phosphate accumulation.
      Further, rats administered antidepressants after pretreatment with neomycin to
      inhibit metabolic utilization of phosphoinositides were behaviorally evaluated in
      the forced swim test. RESULTS: Diverse antidepressants significantly enhanced
      phosphoinositide synthesis. While alpha-methylserotonin increased inositol
      phosphate accumulation, this effect was significantly accentuated in hippocampal
      or cortical tissues pre-incubated in the presence of imipramine, desipramine,
      fluoxetine, paroxetine, or maprotiline. Drug-induced behavioral antidepressant
      effects were reversed by neomycin pretreatment, whereas neomycin alone did not
      alter basal immobility times. CONCLUSIONS: Antidepressants probably exert tandem
      neurochemical effects by increasing synaptic monoamine concentrations and by
      producing phosphoinositides used in 5HT(2) receptor signaling. This combination
      of actions may constitute the mechanism of at least the acute behavioral effects
      of the drugs and could implicate aberrant neurolipid signaling in the
      pathophysiology of depression.

PMID- 17435994
TI  - Hypervascular multifocal hepatoblastoma: dynamic gadolinium-enhanced MRI findings
      indistinguishable from infantile hemangioendothelioma.
AB  - In this case report we describe a neonate with multifocal hypervascular
      hepatoblastoma indistinguishable from infantile hemangioendothelioma on dynamic
      gadolinium-enhanced MRI. Review of the literature revealed a description of a
      hypervascular form of solitary hepatoblastoma visualized using sonography and CT.
      Our case is unique in that it illustrates centripetal fill-in of multifocal
      hepatoblastoma on dynamic gadolinium-enhanced MRI. MRI has several advantages
      over CT in the characterization and follow-up of neonatal liver tumors. These
      advantages include the lack of ionizing radiation, as well as an ability to
      visualize vascular structures that is less dependent upon the timing of contrast
      material administration. This case further highlights the difficulty in
      discriminating between infantile hemangioendothelioma and hepatoblastoma in
      radiology, particularly in a multifocal hypervascular variant of hepatoblastoma.

PMID- 17435995
TI  - From scratch to value: engineering Escherichia coli wild type cells to the
      production of L-phenylalanine and other fine chemicals derived from chorismate.
AB  - Recombinant strains of Escherichia coli K-12 for the production of the three
      aromatic amino acids (L-phenylalanine, L-tryptophan, L-tyrosine) have been
      constructed. The largest demand is for L-phenylalanine (L-Phe), as it can be used
      as a building block for the low-calorie sweetener, aspartame. Besides L-Phe, an
      increasing number of shikimic acid pathway intermediates can be produced from
      appropriate E. coli mutants with blocks in this pathway. The last common
      intermediate, chorismate, in E. coli not only serves for production of aromatic
      amino acids but can also be used for high-titer production of non-aromatic
      compounds, e.g., cyclohexadiene-transdiols. In an approach to diversity-oriented
      metabolic engineering (metabolic grafting), platform strains with increased flux
      through the general aromatic pathway were created by suitable gene deletions,
      additions, or rearrangements. Examples for rational strain constructions for L
      phenylalanine and chorismate derivatives are given with emphasis on genetic
      engineering. As a result, L-phenylalanine producers are available, which were
      derived through several defined steps from E. coli K-12 wild type. These mutant
      strains showed L-phenylalanine titers of up to 38 g/l of L-phenylalanine (and up
      to 45.5 g/l using in situ product recovery). Likewise, two cyclohexadiene
      transdiols could be recovered.

PMID- 17435996
TI  - Diagnostic impact of PET with 18F-FDG, 18F-DOPA and 3-O-methyl-6-[18F]fluoro-DOPA
      in recurrent or metastatic medullary thyroid carcinoma.
AB  - PURPOSE: In patients with medullary thyroid carcinoma (MTC), rising levels of the
      tumour markers calcitonin and CEA after primary surgery indicate tumour
      recurrence or metastases. The only chance of cure is the resection of localised
      tumour tissue. For positron emission tomography (PET) with (18)F
      fluorodeoxyglucose ((18)F-FDG) and (18)F-dihydroxyphenylalanine ((18)F-DOPA),
      sensitivities of 78% and 63% have been reported, but in a considerable percentage
      of MTC patients the source of tumour marker elevation is not detected. The aim of
      this retrospective data evaluation was to compare the value of PET with (18)F
      FDG, (18)F-DOPA and the amino acid tracer 3-O-methyl-6-[(18)F]fluoro-DOPA ((18)F
      OMFD) in the detection of MTC recurrence. METHODS: Fifteen patients with elevated
      calcitonin were investigated with PET as part of their individual clinical work
      up. All patients underwent (18)F-FDG PET and (18)F-DOPA PET, and ten patients
      underwent (18)F-OMFD PET. RESULTS: With (18)F-FDG, seven patients showed foci in
      the neck, mediastinum, upper abdomen or bone. In seven patients, (18)F-DOPA
      revealed suspicious foci; five of these seven patients showed partially
      corresponding uptake of (18)F-FDG in the neck and mediastinum. Two of these
      patients underwent surgery and metastases were verified. With (18)F-OMFD, a small
      focus in the liver was suspected in one patient without a correlate on (18)F-FDG
      PET, (18)F-DOPA PET or conventional imaging. CONCLUSION: (18)F-FDG and (18)F-DOPA
      showed foci that were highly suspicious for local recurrence or metastasis of
      MTC, although histological verification in these patients with numerous previous
      surgical interventions was performed in only two patients. The amino acid tracer
      (18)F-OMFD had no diagnostic impact in these patients.

PMID- 17435997
TI  - Trichosanthin down-regulated p210Bcr-Abl and enhanced imatinib-induced growth
      arrest in chronic myelogenous leukemia cell line K562.
AB  - PURPOSE: Trichosanthin (TCS), an active component extracted from the root tubers
      of traditional Chinese medical herb Tian-Hua-Fen of the Cucurbitaceae family, has
      long been used for medical purpose in China; there is increasing interest in
      developing TCS as cancer therapeutic agents. The present study was to investigate
      the growth arrest of K562 cells and its molecular mechanisms, which the drugs
      induced by TCS and the possible functional interaction of TCS with imatinib
      (STI571) to K562 cells. METHODS: Trypan blue exclusive staining was used to
      access the cell growth inhibition; western blot was used to evaluate the p210(Bcr
      Abl), phosphorylated tyrosine kinase (PTK), and some signaling molecules
      involving in cell proliferation and apoptosis in K562 cells. RESULTS: TCS and
      imatinib inhibited K562 cells at a time- and dose-dependent manners,
      respectively; TCS down-regulated p210(Bcr-Abl) at a time- and dose-dependent
      manners; TCS synergistically enhanced imatinib-induced K562 cell growth arrest
      and down-regulation of p210(Bcr-Abl), PTK activities, procaspase-3, Hsp90,NF
      kappaB and PKC. CONCLUSION: The results suggest that TCS not only by itself
      involves but also synergizes activities of imatinib to induce K562 cell growth
      arrest, down-regulation of p210(Bcr-Abl) and its downstream signals and to
      stimulate the effect of the tyrosine kinase inhibition.

PMID- 17435998
TI  - Chemotaxis-induced spatio-temporal heterogeneity in multi-species host-parasitoid
      systems.
AB  - When searching for hosts, parasitoids are observed to aggregate in response to
      chemical signalling cues emitted by plants during host feeding. In this paper we
      model aggregative parasitoid behaviour in a multi-species host-parasitoid
      community using a system of reaction-diffusion-chemotaxis equations. The
      stability properties of the steady-states of the model system are studied using
      linear stability analysis which highlights the possibility of interesting
      dynamical behaviour when the chemotactic response is above a certain threshold.
      We observe quasi-chaotic dynamic heterogeneous spatio-temporal patterns, quasi
      stationary heterogeneous patterns and a destabilisation of the steady-states of
      the system. The generation of heterogeneous spatio-temporal patterns and
      destabilisation of the steady state are due to parasitoid chemotactic response to
      hosts. The dynamical behaviour of our system has both mathematical and ecological
      implications and the concepts of chemotaxis-driven instability and coexistence
      and ecological change are discussed.

PMID- 17435999
TI  - Novel group VII histidine kinase HwHhk7B from the halophilic fungi Hortaea
      werneckii has a putative role in osmosensing.
AB  - Histidine kinases (HKs) are abundant among prokaryotes and have been
      characterized in fungi and plants, although not yet in animals. These enzymes
      regulate diverse processes, including adaptation to osmotic stress and virulence
      of plant and animal pathogens. Here, we report the cloning, characterization and
      phylogenetic analysis of HwHHK7A and HwHHK7B, HK genes from the fungi Hortaea
      werneckii, a proposed model system for studying salt tolerance in eukaryotes. The
      two HwHhk7 isoforms are 96.7% identical in amino-acid sequence and have a typical
      eukaryotic hybrid HK domain composition. On the bases of the conserved sequence
      of the H box, they are classified into the group VII ascomycete HKs. For the
      HwHhk7B protein, the autokinase activity was demonstrated in vitro. The salt
      responsive expression of the HwHHK7 genes and the increased osmotolerance of a
      wild-type Saccharomyces cerevisiae strain expressing the HwHHK7B gene lead us to
      speculate that these newly identified HKs have roles in osmosensing.

PMID- 17436000
TI  - Activin A suppresses interleukin-1-induced matrix metalloproteinase 3 secretion
      in human chondrosarcoma cells.
AB  - The objective was to investigate the effect of activin A on matrix
      metalloproteinase 3 (MMP-3) production and to identify the role of activin A in
      chondroprotection. SW1353 cells, a human chondrosarcoma cell line, were
      stimulated with interleukin (IL) 1alpha and tumor necrosis factor (TNF) alpha,
      and the concentrations of activin A, follistatin, and MMP-3 secreted into the
      culture media were measured by enzyme-linked immunosorbent assay (ELISA). Activin
      A was added to cell cultures in the presence of IL-1alpha or TNFalpha to
      determine its effect on the production of MMP-3 and sulfated glycosaminoglycan
      (sGAG) (measured by Alcian blue assay). To study the mechanism responsible for
      the chondroprotective effects of activin A, the production of IL-1 receptor
      antagonist (IL-1ra) and tissue inhibitor for metalloproteinases 1 (TIMP-1) was
      examined by ELISA. Addition of IL-1alpha did not affect the production of activin
      A by cultured SW1353 cells. IL-1alpha and activin A inhibited the production of
      follistatin. Stimulation of SW1353 cells with activin A suppressed IL-1alpha
      induced, but not TNFalpha-induced, MMP-3 expression. Activin A had no effect on
      the production of sGAG, IL-1ra, or TIMP-1, although it suppressed the induction
      of TIMP-1 and IL-1ra by IL-1alpha. This novel finding of MMP-3 inhibition by
      activin A suggests a new role of activin A in cartilage remodeling. Activin A may
      have therapeutic potential for preventing cartilage degradation.

PMID- 17436001
TI  - Catastrophic antiphospholipid syndrome presented with severe hypertension, adult
      respiratory distress syndrome and unilateral adrenal haemorrhagic infarction.
AB  - We are reporting a case of catastrophic antiphospholipid syndrome (CAPS) in an
      adult female manifested with severe hypertension followed by adrenal haemorrhagic
      infarction and adult respiratory distress syndrome. Adrenal involvement appears
      to be exceedingly high in CAPS and adult respiratory distress syndrome (ARDS) is
      the prevailing pulmonary manifestation in this condition, compared with these
      impediments in patients with simple antiphospholipid syndrome (APS). Even though
      the above manifestations are well recognized, their combination as an initial
      presentation of CAPS is uncommon.

PMID- 17436002
TI  - Intra-articular injection of hyaluronate and indomethacin in rabbits with antigen
      induced arthritis.
AB  - Combined effects of hyaluronate and indomethacin in the treatment of rabbits with
      antigen-induced arthritis (AIA) were evaluated by assessing joint swelling, C
      reactive protein (CRP) and prostaglandin E(2) (PGE(2)) levels with periodic intra
      articular (ia) injections of hyaluronate alone (HA group) and with either a low
      or high concentration of indomethacin (LI-HA or HI-HA group). End-point analyses
      included matrix metalloproteinases-3 (MMP-3) activity and macroscopic and
      histological joint examinations. Results demonstrated that treatment in LI-HA and
      HI-HA groups resulted in statistically significant suppression of CRP, PGE(2,
      )and MMP-3 in comparison with those of HA group. Inhibition of serum CRP was only
      observed in LI-HA group. The order of serum MMP-3 inhibition was LI-HA>HI-HA>HA.
      Based on macroscopic and histological analyses of pannus formation, hyperplasia,
      inflammation, joint leakage and erosion, and loss of proteoglycan, the only
      statistically significant improvement was shown in LI-HA group compared to HA
      group and HI-HA group compared to control group.

PMID- 17436004
TI  - [Laboratory diagnosis of rheumatic disease - quo vadis? An integral component of
      rheumatology].

PMID- 17436003
TI  - Visual assessment of uroflowmetry curves: description and interpretation by
      urodynamists.
AB  - The aim of study is to verify the aptitude of urodynamists to carry out an
      objective description of uroflowmetric parameters and to formulate a diagnostic
      suspicion by using merely the visual interpretation of uroflowmetry curves. An
      anonymous questionnaire including ten uroflowmetry curves was administered to
      urologists participating in the XXVI Congress of the Italian Society of
      Urodynamics (SIUD). To evaluate the accuracy in the description of uroflowmetry
      pattern, we asked to classify as "normal" or "abnormal" all uroflowmetry
      parameters; to assess the capability to outline a diagnostic suspicion, we
      requested to choose one out of six possible diagnoses. Inter- and intraobserver
      agreements were calculated. We overall recruited 105 questionnaires out of 300
      urologists attending the SIUD Congress. Substantial interobserver agreement was
      obtained for maximum flow rate, average flow rate, flow time, and voiding time
      (K=0.79, 0.79, 0.77, and 0.72), whereas substantial intraobserver agreements were
      evidenced for maximum flow rate and flow time (K=0.70 and 0.63). We noted
      substantial agreement for the "No abnormalities" diagnosis (K=0.72), fair
      agreement for "Urethral stricture" (K=0.30), and slight agreement for both
      "Benign prostatic obstruction" and "Bladder outflow obstruction" (K=0.17 and
      0.20); moreover, we reported a moderate intraobserver agreement (K=0.05) on
      diagnostic suspicion. Maximum flow rate, average flow rate, flow time, and
      voiding time are properly assessed by the large part of urodynamists. Flow curves
      from healthy men or from patients with urethral stricture or benign prostatic
      obstruction are easily recognizable. Long experience and daily practice may make
      the difference in the assessment of uroflowmetry curves.

PMID- 17436005
TI  - [Regulation of apoptosis in aggressive fibroblasts].
AB  - Apoptosis is a central physiological mechanism for maintaining cellular stability
      in tissue. Synovial fibroblasts, which play a central role in the pathogenesis of
      rheumatoid arthritis (RA), show a resistance to apoptosis. Several molecular
      mechanisms are involved in such resistance. Thus, soluble Fas can bind Fas
      ligands (Fas-L) and hinder Fas-L induced apoptosis in fibroblasts. SUMO-1 (a
      small ubiquitin-like modifier) attaches to proteins post-translationally. This
      appears to be significantly involved in apoptosis resistance in RA fibroblasts.
      SUMO-1 levels are substantially increased in synovial fibroblasts from RA
      patients. A change in the post-translational SUMOlation pattern could represent a
      new target for changing the stable activation of synovial fibroblasts in RA.

PMID- 17436006
TI  - Total elbow arthroplasty in patients who have elbow fractures caused by gunshot
      injuries: 8- to 12-year follow-up study.
AB  - INTRODUCTION: In this retrospective study, we aimed to present 8-12-year clinical
      and radiographic evaluation of total elbow arthroplasty in young patients who had
      open fractures due to gunshot injuries. MATERIALS AND METHODS: The study included
      a consecutive series of seven patients who had insertion of total elbow
      prosthesis (semi-constrained type) for the treatment of comminuted intra
      articular elbow fractures resulting from gunshot injuries between 1994 and 1998.
      All patients were male and the mean age at the time of operation was 23 years.
      RESULTS: The average time from the original fracture to the joint replacement was
      26 months (range 14-39). The mean follow-up period was 117 +/- 15 months. At the
      time of the latest follow-up, 5 of 7 elbows had a poor result. Radiological
      evaluations revealed that three patients had ulnar and two patients had humeral
      component loosening at the last follow-up examination. No intra-operative
      complications were observed. In the long-term evaluation, two patients had
      prosthesis loosening that resulted from deep infection and three patients had
      aseptic loosening that necessitated re-operation. The prosthesis removal was
      performed. CONCLUSION: As a result, the patients in whom we implemented total
      elbow prosthesis in comminuted elbow fractures due to gunshot wounds seemed to
      get back into active life in the early period without any problem and it seemed
      that their pain disappeared and their functional capacity increased. In the long
      period, however, these values showed a distinct decrease with the same patients.

PMID- 17436008
TI  - Estimation of pediatric skeletal age using geometric morphometrics and three
      dimensional cranial size changes.
AB  - This paper presents a method for estimating the skeletal age of children based on
      the centroid size of their face and their basicranium, derived from the three
      dimensional coordinates of anatomical landmarks. The sample consists of computed
      tomography scans of 127 children (54 boys, 73 girls) of mixed origin living in
      the area of Toulouse (France), ranging in age from a few days to 18 years. The
      purpose of the present investigation was, first, to increase the variety of age
      related structures theoretically available for pediatric skeletal age estimation
      and, second, to devise a method that can be applicable from early postnatal age
      to the end of adolescence with a satisfactory accuracy independent of age and
      even a better accuracy with greater age. We examined the relationship between the
      chronological age and the centroid size, calculated by using geometric
      morphometric methods and a linear model. With the aid of cross-validations, the
      statistical analysis indicates that the centroid size of the facial skeleton can
      be used an age-related variable without any loss of accuracy with increased age,
      contrary to most of the methods of pediatric age estimation. The standard error
      was always lower or equal to 2.1 years (at the 95% confidence level) and
      decreased in our sub-sample of older children represented by a larger number of
      individuals.

PMID- 17436007
TI  - Dilation of intercellular spaces is associated with laryngo-pharyngeal reflux: an
      ultrastructural morphometric analysis of laryngeal epithelium.
AB  - Gastroesophageal reflux disease (GERD) can be associated with ear, nose, and
      throat signs and symptoms, a condition often referred to as laryngopharyngeal
      reflux (LPR). However, the morphologic alterations of laryngeal mucosa associated
      with LPR are currently poorly understood. Since the dilation of intercellular
      spaces (DIS) between squamous epithelial cells is considered a morphologic marker
      of acid damage to esophageal mucosa in GERD, we evaluated whether similar changes
      can be detected in the laryngeal epithelium of patients affected by LPR. The
      study group included 15 patients affected by LPR and 7 normal controls, who
      underwent laryngeal biopsies at the interarytenoid area. Specimens were routinely
      processed for light microscopic and ultrastructural examination. The
      intercellular spaces were measured in electron microscopy images using a computer
      assisted morphometric system. Ultrastructural analysis demonstrated an irregular
      intercellular space dilation in specimens from the group of patients with LPR.
      Another ultrastructural abnormality observed in a minority of patients was the
      presence of numerous cytoplasmic vacuoles. Computer assisted morphometric
      analysis demonstrated that the intercellular space between squamous cells was
      significantly wider in patients with LPR than in control subjects (411.7 nm +/-
      188.6 SD vs. 155.8 nm +/- 56.4 SD, P = 0.003). These data indicate that
      ultrastructural evidence of DIS of epithelial cells may be a morphologic marker
      of acid reflux, as already described in esophageal mucosa. If this result will be
      confirmed in larger series it may provide a useful diagnostic tool for the
      identification of LPR.

PMID- 17436009
TI  - Forensic efficiency of microsatellites and single nucleotide polymorphisms on the
      X chromosome.
AB  - Polymorphisms located on the X chromosome are being increasingly used in forensic
      studies. However, they have not been studied as extensively as the autosomal and
      Y-linked polymorphisms. Therefore, we planned to study the population genetics of
      two sets of X-linked markers, including short-tandem repeats (STRs) and single
      nucleotide polymorphisms (SNPs), and particularly analyze the differences at the
      microgeographical level. Six X-linked STRs (DXS 9895, DXS 7132, DXS 9898, DXS
      6789, GATA 172D05, and DXS 7130) and ten SNPs (rs1229078, rs1544545, rs4442270,
      rs1874111, rs5968332, rs1166756, rs12849634, rs5932595, rs203648, and rs611711)
      were studied in two population samples from Cantabria, northern Spain, a mixed
      coastal population and a relatively isolated small population in the Pas valley.
      There were statistically significant differences in allelic frequencies of the
      six STRs studied between both populations. On the other hand, only one out of ten
      SNPs studied showed between-population differences. Overall Fst values were 0.4
      2.9% and 1.8-2.2% for the STRs and the SNPs, respectively. The overall power of
      discrimination for female samples was higher than 99.99% for both groups of
      markers. Therefore, these sets of X-linked STRs and SNPs seem to be potentially
      useful in forensic genetics, but care should be taken when interpreting results
      from cases that originate from small and relatively isolated populations.

PMID- 17436010
TI  - Donor B cells in splenic follicles of experimental pulmonary allograft
      recipients.
AB  - BACKGROUND: After transplantation, passenger leukocytes move to lymphoid organs
      of the recipient. These cells appear to initiate allograft rejection, but they
      also might be involved in tolerance induction. MATERIALS AND METHODS: Orthotopic
      left lung transplantation was performed in the Dark Agouti to Lewis rat strain
      combination with no immunosuppression. Recipient spleens were removed at
      intervals of 24 h until day 6 after transplantation. For comparison, spleens from
      renal allograft recipients were analysed. Donor-derived major histocompatibility
      complex (MHC) class II antigens were detected by monoclonal antibody OX76. In
      double-staining experiments with antibodies specific for leukocyte
      subpopulations, their localisation and identity was analysed. RESULTS: OX76
      positive leukocytes were already detected in recipient spleens on day 1 post
      transplantation. They increased in number until day 3 and decreased in number
      thereafter. Most of them were localised in splenic follicles and expressed the B
      cell variant of CD45R and IgG. Cell surface antigens typical for other leukocyte
      subpopulations were not detected. In the spleens of renal allograft recipients,
      only few donor-derived cells were seen. CONCLUSION: After lung transplantation,
      numerous MHC class II-positive B cells migrate to the splenic follicles of the
      recipient. These cells might, in part, be responsible for immunologic differences
      observed between renal and pulmonary allografts.

PMID- 17436011
TI  - Opioid use determines success of videothoracoscopic splanchnicectomy in chronic
      pancreatic pain patients.
AB  - OBJECTIVE: Videoscopic splanchnicectomy (VSPL) is a method of pain relief in
      chronic pancreatitis patients. Because this method is not equally effective in
      all patients, this study was designed to identify the factors determining the
      unfavorable results of VSPL. MATERIALS AND METHODS: This is a non-randomized
      prospective case-controlled study designed to compare a group of patients
      suffering from chronic pancreatitis treated with VSPL (N = 48) versus a group of
      patients treated symptomatically (N = 42). The outcome was measured as the
      intensity of pain ailments [visual analog scale (VAS)-pain scale] and subjective
      satisfaction of the patients from the surgical treatment [Functional Assessment
      of Chronic Illness Therapy-Treatment Satisfaction (FACIT-TS)]. The predictive
      variables considered in this study were: age, sex, emotional status, social
      support (the two last variables were measured by subscales of quality-of-life
      questionnaire from the group of FACIT), history of previous surgical treatment,
      and opioid use for at least 3 months before VSPL. The follow-up was 18 months.
      Logistic regression was performed using dichotomized pain as outcome variable:
      high score more than 66.7 on VAS scale and low under 50 points on VAS scale 18
      months after VSPL. RESULTS: VSPL significantly reduced the pain ailments at all
      points of the study when compared to the control. However, the pain intensity at
      the end of the study was higher than directly after the surgery. In the patients
      treated with opioids before the surgery, the pain intensity was significantly
      higher than in the patients not using this group of drugs. Logistic regression
      revealed that opioid administration before VSPL was the most important predictor
      of high pain scores 18 months after the surgery. CONCLUSION: When planning the
      VSPL in the treatment of pain in patients suffering from chronic pancreatitis, it
      is necessary to take into consideration the previous chronic use of opioids, as
      this variable can significantly influence poorer results of this surgical pain
      management.

PMID- 17436013
TI  - Hypothesis: proposals for the management of a neonate at risk of hyperammonaemia
      due to a urea cycle disorder.
AB  - It is difficult to prevent hyperammonaemia in patients with urea cycle disorders
      that present in the newborn period. This is true, even if treatment is started
      prospectively because of an affected relative. We propose several additional
      measures that could be used in conjunction with conventional therapy to improve
      the metabolic control. Catabolism could be reduced by delivering the babies by
      elective caesarean section, by starting intravenous glucose immediately after
      delivery and, possibly, by using beta-blockers or octreotide and insulin. The
      effectiveness of sodium benzoate and sodium phenylbutyrate might be increased by
      giving phenobarbital to the mother before delivery and subsequently to the baby
      to induce the enzymes for conjugation. We would expect the proposed measures to
      reduce the risk of hyperammonaemia and to improve the outcome for these patients.
      They have not, however, previously been used in this context, so families would
      need to be counselled carefully and controlled studies should be undertaken.

PMID- 17436014
TI  - Nanoduct sweat testing for rapid diagnosis in newborns, infants and children with
      cystic fibrosis.
AB  - Determination of chloride concentration in sweat is the current diagnostic gold
      standard for Cystic Fibrosis (CF). Nanoduct is a new analyzing system measuring
      conductivity which requires only 3 microliters of sweat and gives results within
      30 minutes. The aim of the study was to evaluate the applicability of this system
      in a clinical setting of three children's hospitals and borderline results were
      compared with sweat chloride concentration. Over 3 years, 1,041 subjects were
      tested and in 946 diagnostic results were obtained. In 95 children, Nanoduct
      failed (9.1% failure rate), mainly due to failures in preterm babies and
      newborns. Assuming 59 mmol/L as an upper limit of normal conductivity, all our 46
      CF patients were correctly diagnosed (sensitivity 100%, 95% CI: 93.1-100;
      negative predicted value 100% (95% CI: 99.6-100) and only 39 non CF's were false
      positive (39/900, 4.3%; specificity 95.7%, 95%CI: 94.2-96.9, positive predicted
      value 54.1% with a 95%CI: 43.4-65.0). Increasing the diagnostic limit to 80
      mmol/L, the rate fell to 0.3% (3/900). CF patients had a median conductivity of
      115 mmol/L; the non-CF a median of 37 mmol/L. In conclusion, the Nanoduct test is
      a reliable diagnostic tool for CF diagnosis: It has a failure rate comparable to
      other sweat tests and can be used as a simple bedside test for fast and reliable
      exclusion, diagnosis or suspicion of CF. In cases with borderline conductivity
      (60-80 mmol/L) other additional methods (determination of chloride and
      genotyping) are indicated.

PMID- 17436012
TI  - Mechanotransduction and auditory transduction in Drosophila.
AB  - Insects are utterly reliant on sensory mechanotransduction, the process of
      converting physical stimuli into neuronal receptor potentials. The senses of
      proprioception, touch, and hearing are involved in almost every aspect of an
      adult insect's complex behavioral repertoire and are mediated by a diverse array
      of specialized sensilla and sensory neurons. The physiology and morphology of
      several of these have been described in detail; genetic approaches in Drosophila,
      combining behavioral screens and sensory electrophysiology with forward and
      reverse genetic techniques, have now revealed specific proteins involved in their
      differentiation and operation. These include three different TRP superfamily ion
      channels that are required for transduction in tactile bristles, chordotonal
      stretch receptors, and polymodal nociceptors. Transduction also depends on the
      normal differentiation and mechanical integrity of the modified cilia that form
      the neuronal sensory endings, the accessory structures that transmit stimuli to
      them and, in bristles, a specialized receptor lymph and transepithelial
      potential. Flies hear near-field sounds with a vibration-sensitive, antennal
      chordotonal organ. Biomechanical analyses of wild-type antennae reveal non
      linear, active mechanical properties that increase their sensitivity to weak
      stimuli. The effects of mechanosensory and ciliary mutations on antennal
      mechanics show that the sensory cilia are the active motor elements and indicate
      distinct roles for TRPN and TRPV channels in auditory transduction and
      amplification.

PMID- 17436015
TI  - Osteoporosis in juvenile idiopathic arthritis--a practical approach to diagnosis
      and therapy.
AB  - In all subgroups of juvenile idiopathic arthritis, a decrease in bone mass has
      been described in a high percentage of children. Recently, new pathogenetic
      concepts have identified muscle mass as the strongest predictor of bone mass and
      bone is now recognized as part of the musculoskeletal system. In addition, the
      sophisticated use of bone densitometry in pediatrics, including new measurement
      techniques, has provided the tools for a reliable assessment. A standardized
      diagnostic approach to the musculoskeletal system, including prophylaxis and
      therapy, is, therefore, mandatory in all children with JIA who do not achieve
      rapid remission. In this review, diagnostic and therapeutic options are being
      described and possibilities to incorporate them into clinical practice are
      suggested.

PMID- 17436016
TI  - Is Familial Mediterranean Fever a thrombotic disease or not?
AB  - The aim of our study was to show how the progression and severity of Familial
      Mediterranean Fever (FMF) is affected by procoagulant activity and alterations in
      the markers of thrombosis and fibrinolysis. The study cohort comprised 64 FMF
      patients who were classified as attack-free patients (Group 1; n = 34 patients,
      aged 3-19 years) and attack patients (Group 2; n = 30 patients, aged 3-21 years).
      All patients were on colchicine treatment with the exception the newly diagnosed
      patients in Group 2. A total of 14 healthy subjects between 5-12 years of age
      were enrolled as controls (Group 3). Laboratory tests, including leukocyte and
      thrombocyte counts, erythrocyte sedimentation rate, CRP, fibrinogen, PT, aPTT,
      Factor VIII, vW factor, D-dimer, P-selectin, tPA and PAI-1, were carried out on
      all patients. Inflammation continued both during the attack and attack-free
      period in FMF. The prolongation of PT was observed during attacks (PT = 13.6 s in
      Group 2, and PT = 12.6 s in Group 3; p = 0.002). tPA levels increased in FMF
      patients (tPA levels of group 1, 2 and 3 were 12.6, 13.2 and 9.7 ng/ml,
      respectively; p = 0.01). P-selectin was lower in both patient groups than in the
      control group. During attack periods PAI-1 levels increased (PAI-1 level of Group
      1: 89.6 ng/ml and PAI-1 level of Group 2: 335.7 ng/ml, p = 0.000). Inflammation
      with increased acute phase reactants continued during both attack and attack-free
      periods in FMF patients. Prolongation of PT and differences in tPA and P-selectin
      levels suggest that hypercoagulability may have a role in the etiopathogenesis of
      FMF. It may be possible to use PAI-1 as a marker for the attacks of FMF.

PMID- 17436017
TI  - Could lipid infusion be a risk for parenteral nutrition-associated cholestasis in
      low birth weight neonates?
AB  - To assess whether lipid infusion could be a risk factor for parenteral nutrition
      associated cholestasis (PNAC) in low birth weight neonates, 22 newborns with
      cholestasis (29.8 +/- 1.6 weeks, 1298 +/- 217 g) were compared with 22 without
      cholestasis (29.5 +/- 1.7 weeks, 1286 +/- 363 g). The mean level of peak direct
      bilirubin for the cholestasis group was 4.6 mg/dl compared to 1.2 mg/dl for the
      noncholestasis group. A univariate analysis revealed that PNAC was significantly
      related to duration of fasting (p = 0.008) and parenteral nutrition (p < 0.0001),
      days of antibiotics use (p = 0.025), positive C-reactive protein (p = 0.018) or
      gastric culture (p = 0.018), and feeding intolerance (p < 0.0001). Total amino
      acid amount (p < 0.0001), total lipid amount (p < 0.0001), and average daily
      lipid amount (p = 0.002) were significantly higher in the cholestasis group than
      in the noncholestasis group. Conversely, prenatal administration of dexamethasone
      was a significant protective factor of PNAC (p = 0.008). Logistic regression
      analysis revealed that the cumulative amount of lipid infusion was an independent
      risk factor for PNAC (p = 0.041; OR 1.174; CI 1.007-1.369). We suggest that
      decreasing the cumulative load of amino acids and intralipids with early trophic
      feeding, control of infection, and prenatal administration of dexamethasone could
      possibly attenuate the severity of PNAC.

PMID- 17436018
TI  - Effects of silymarin on the spontaneous proliferation and cell cycle of human
      peripheral blood leukemia T cells.
AB  - Silymarin is a polyphenolic flavonoid that has a strong antioxidant activity and
      exhibits anti-carcinogenic, anti-inflammatory, and cytoprotective effects.
      Although its hepatoprotective effect has been well documented, the effect of
      silymarin on T cells is largely unknown. The purpose of this study was to analyze
      the effects of the silymarin on the proliferation and cell cycle progression of
      Jurkat cells, a human peripheral blood leukemia T cell line. Cells were incubated
      with various concentrations of silymarin for 24-72 h and examined for cell growth
      and proliferation using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) and DNA 5-bromo 2'-deoxyuridine (BrdU) colorimetric assays. Cell
      cycle analysis by flow cytometry was also performed using propidium iodide
      staining. Results of the study revealed that silymarin increased proliferation of
      Jurkat cells at 50-400 microM concentrations with 24 h exposure, confirmed by
      both MTT and BrdU assays. However, Jurkat incubation with silymarin at higher
      concentrations of 400 microM for 48 h and 200-400 microM for 72 h caused
      inhibition of DNA synthesis, cell cycle arrest at the G2/M phase and significant
      cell death. Results of the present study also revealed a similarity of cell
      growth patterns between Jurkat, U937 and RPMI 8866 cells. In conclusion, this
      study demonstrated an in vitro growth stimulatory effect of silymarin on leukemia
      cells with monocyte, T and B cell origin that has not been previously reported
      for either solid tumors or other leukemia cells, suggesting a possible specific
      stimulatory effect of silymarin on the key cells of the immune system.

PMID- 17436019
TI  - Intragenic deletion in the LARGE gene causes Walker-Warburg syndrome.
AB  - Intragenic homozygous deletions in the Large gene are associated with a severe
      neuromuscular phenotype in the myodystrophy (myd) mouse. These mutations result
      in a virtual lack of glycosylation of alpha-dystroglycan. Compound heterozygous
      LARGE mutations have been reported in a single human patient, manifesting with
      mild congenital muscular dystrophy (CMD) and severe mental retardation. These
      mutations are likely to retain some residual LARGE glycosyltransferase activity
      as indicated by residual alpha-dystroglycan glycosylation in patient cells. We
      hypothesized that more severe LARGE mutations are associated with a more severe
      CMD phenotype in humans. Here we report a 63-kb intragenic LARGE deletion in a
      family with Walker-Warburg syndrome (WWS), which is characterized by CMD, and
      severe structural brain and eye malformations. This finding demonstrates that
      LARGE gene mutations can give rise to a wide clinical spectrum, similar as for
      other genes that have a role in the post-translational modification of the alpha
      dystroglycan protein.

PMID- 17436020
TI  - Genetic liability to schizophrenia in Oceanic Palau: a search in the affected and
      maternal generation.
AB  - While liability to schizophrenia (Scz) is due to genetic and environmental
      factors, specific factors are largely unknown. We postulate a two-hit model for
      Scz, in which initial liability is generated during fetal brain development: this
      "hit" is precipitated by environmental stressors biologically interacting with
      maternal genetic vulnerability to the stress. Additional liability to Scz is
      generated by individual genetic vulnerability. To evaluate these putative levels
      of vulnerability, we search in the genome of both affected individuals and their
      mothers for variation that differs, statistically, from that in the general
      population. For parental analyses, mothers were treated as "affected," rather
      than their offspring, and the fathers were treated as "controls". We used a
      sample from the Palauan population: 175 individuals diagnosed with Scz, broadly
      defined; 87 mothers and 45 fathers of affected individuals. Pedigree and
      diagnostic data were available on 2,953 living and deceased subjects. DNA from
      553 individuals was genotyped for short tandem repeats (STR) spaced approximately
      every 10 cM across the genome. We tested for association between affection status
      and STR alleles; such an approach was reasonable, despite the widely spaced
      markers, because this population has far-ranging linkage disequilibrium (LD).
      Results for the truly affected individuals were modest, whereas results from the
      maternal generation were promising. For a recessive model and a test for excess
      allele matching across mothers, significant findings occurred for D20S481,
      D10S1221, D6S1021, D13S317, and D18S976. Regions in which at least two adjacent
      markers produced substantial association statistics include 2p12-11.2, 2q24.1
      32.1, 6q12-14.1, 10q23.2-24.21, 12q23.2-24.21 and 17q23.2-23.3.

PMID- 17436022
TI  - Hypoxia tolerance associated with activity reduction is a key adaptation for
      Laternula elliptica seasonal energetics.
AB  - Seasonal dormancy is a widespread mechanism for reducing energy expenditure
      during periods of low energy availability. Seasonal variation in activity and the
      cost of pumping water through the siphons were investigated to estimate the
      importance of activity regulation to the seasonal energy budget of the Antarctic
      clam, Laternula elliptica. In the laboratory, a metabolic rate of 26.35 micromol
      O(2) h(-1) was estimated for a 50-mm shell length L. elliptica pumping water at 
      0.4 degrees C. In the field, the proportion of time siphons were visible at the
      sediment surface varied seasonally (32% visible in June/July compared to 86% in
      December/January). L. elliptica were actively pumping for a minimum of 19% of
      each 24-h period during winter (August) compared to a summer maximum when animals
      were actively pumping for 73% of the time (February). This resulted in a 3.7-fold
      seasonal difference in the calculated energy consumption of a 50-mm L. elliptica
      (19.2 micromol O(2) h(-1) in February versus 5.0 micromol O(2) h(-1) in August),
      which closely matches the 3.0-fold seasonal variation in metabolic rate found
      previously. Seasonal variation in activity could therefore be responsible for
      much of the seasonal difference in energy consumption of L. elliptica. Inter
      annual variation in timing of the seasonal activity maxima (January 2004 and
      March 1999) was correlated with variation in the timing of the summer plankton
      bloom in Ryder Bay. In the laboratory, periods of extended siphon closure (133 +/
      114 min, mean +/- SD) were accompanied by long periods of heart arrhythmia (167
      +/- 135 min), during which time blood oxygen levels dropped to values close to
      zero. Heart arrhythmia is most likely part of a hypo-metabolic adaptation to
      reduce energy costs during extended periods of siphon closure. Physiological and
      behavioural dormancy, with associated hypoxia tolerance, appear to be key
      mechanisms controlling the seasonal energy budget of L. elliptica.

PMID- 17436021
TI  - Hepatic morphological alterations, glycogen content and cytochrome P450
      activities in rats treated chronically with N(omega)-nitro-L-arginine methyl
      ester (L-NAME).
AB  - Chronic treatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME),
      an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension mediated
      partly by enhanced angiotensin-I-converting enzyme (ACE) activity. We examined
      the influence of L-NAME on rat liver morphology, on hepatic glycogen,
      cholesterol, and triglyceride content, and on the activities of the cytochrome
      P450 isoforms CYP1A1/2, CYP2B1/2, CYP2C11, and CYP2E1. Male Wistar rats were
      treated with L-NAME (20 mg/rat per day via drinking water) for 2, 4, and 8 weeks,
      and their livers were then removed for analysis. Enzymatic induction was produced
      by treating rats with phenobarbital (to induce CYP2B1/2), beta-naphthoflavone (to
      induce CYP1A1/2), or pyrazole (to induce CYP2E1). L-NAME significantly elevated
      blood pressure; this was reversed by concomitant treatment with enalapril (ACE
      inhibitor) or losartan (angiotensin II AT(1) receptor antagonist). L-NAME caused
      vascular hypertrophy in hepatic arteries, with perivascular and interstitial
      fibrosis involving collagen deposition. Hepatic glycogen content also
      significantly increased. L-NAME did not affect fasting glucose levels but
      significantly reduced insulin levels and increased the insulin sensitivity of
      rats, based on an intraperitoneal glucose tolerance test. Immunoblotting
      experiments indicated enhanced phosphorylation of protein kinase B and of
      glycogen synthase kinase 3. All these changes were reversed by concomitant
      treatment with enalapril or losartan. L-NAME had no effect on hepatic cholesterol
      or triglyceride content or on the basal or drug-induced activities and protein
      expression of the cytochrome P450 isoforms. Thus, the chronic inhibition of NO
      biosynthesis produced hepatic morphological alterations and changes in glycogen
      metabolism mediated by the renin-angiotensin system. The increase in hepatic
      glycogen content probably resulted from enhanced glycogen synthase activity
      following the inhibition of glycogen synthase kinase 3 by phosphorylation.

PMID- 17436023
TI  - Life history patterns shape energy allocation among fishes on coral reefs.
AB  - Although critically important, the link between animal life histories and
      ecosystem energetics is seldom explored. In the pursuit of ecological
      simplification, ecosystem properties are typically described by models based on
      static counts, where organisms are aggregated into trophic- or size-based groups.
      Consequently, output is often based on an assumption that larger group biomass
      equals greater energetic contribution. Here, we modelled the individual growth of
      over 58,000 fishes from 74 genera within a coral reef ecosystem to investigate
      the role and importance of taxon-specific life histories to the division, spatial
      distribution and relative contribution of biomass production within 14 coral reef
      fish families. Rank changes among families in standing biomass to biomass
      production indicated that small cryptic families (e.g. Gobiidae and Blenniidae)
      exhibit collective growth potentials equal to or exceeding those of many other
      common families composed of individuals with body-sizes 1-3 orders of magnitude
      larger. Remaining at high risk of predation throughout their lives as a
      consequence of their small size, these cryptic fishes also provide a constant
      food resource and supply of reproductive energy to coral reefs throughout the
      year. Enhanced further by the strength and diversity of their trophic
      relationships within food webs, the highly productive nature of these small
      cryptic fishes suggests they make a substantial contribution to the flow of
      energy in coral reef ecosystems via predatory pathways. It appears that life
      histories leave a strong imprint on ecosystem energy fluxes and illustrate the
      importance of incorporating taxon-specific features when assigning values to key
      ecosystem processes.

PMID- 17436024
TI  - Seasonal plant water uptake patterns in the saline southeast Everglades ecotone.
AB  - The purpose of this study was to determine the seasonal water use patterns of
      dominant macrophytes coexisting in the coastal Everglades ecotone. We measured
      the stable isotope signatures in plant xylem water of Rhizophora mangle, Cladium
      jamaicense, and Sesuvium portulacastrum during the dry (DS) and wet (WS) seasons
      in the estuarine ecotone along Taylor River in Everglades National Park, FL, USA.
      Shallow soilwater and deeper groundwater salinity was also measured to
      extrapolate the salinity encountered by plants at their rooting zone. Average
      soil water oxygen isotope ratios (delta(18)O) was enriched (4.8 +/- 0.2 per
      thousand) in the DS relative to the WS (0.0 +/- 0.1 per thousand), but
      groundwater delta(18)O remained constant between seasons (DS: 2.2 +/- 0.4 per
      thousand; WS: 2.1 +/- 0.1 per thousand). There was an inversion in interstitial
      salinity patterns across the soil profile between seasons. In the DS, shallow
      water was euhaline [i.e., 43 practical salinity units (PSU)] while groundwater
      was less saline (18 PSU). In the WS, however, shallow water was fresh (i.e., 0
      PSU) but groundwater remained brackish (14 PSU). All plants utilized 100%
      (shallow) freshwater during the WS, but in the DS R. mangle switched to a soil
      groundwater mix (delta 55% groundwater) while C. jamaicense and S. portulacastrum
      continued to use euhaline shallow water. In the DS, based on delta(18)O data, the
      roots of R. mangle roots were exposed to salinities of 25.4 +/- 1.4 PSU, less
      saline than either C. jamaicense (39.1 +/- 2.2 PSU) or S. portulacastrum (38.6 +/
      2.5 PSU). Although the salinity tolerance of C. jamaicense is not known, it is
      unlikely that long-term exposure to high salinity is conducive to the persistence
      of this freshwater marsh sedge. This study increases our ecological understanding
      of how water uptake patterns of individual plants can contribute to ecosystem
      levels changes, not only in the southeast saline Everglades, but also in
      estuaries in general in response to global sea level rise and human-induced
      changes in freshwater flows.

PMID- 17436026
TI  - Mental representation of symbols as revealed by vocabulary errors in two bonobos
      (Pan paniscus).
AB  - Error analysis has been used in humans to detect implicit representations and
      categories in language use. The present study utilizes the same technique to
      report on mental representations and categories in symbol use from two bonobos
      (Pan paniscus). These bonobos have been shown in published reports to comprehend
      English at the level of a two-and-a-half year old child and to use a keyboard
      with over 200 visuographic symbols (lexigrams). In this study, vocabulary test
      errors from over 10 years of data revealed auditory, visual, and spatio-temporal
      generalizations (errors were more likely items that looked like sounded like, or
      were frequently associated with the sample item in space or in time), as well as
      hierarchical and conceptual categorizations. These error data, like those of
      humans, are a result of spontaneous responding rather than specific training and
      do not solely depend upon the sample mode (e.g. auditory similarity errors are
      not universally more frequent with an English sample, nor were visual similarity
      errors universally more frequent with a photograph sample). However, unlike
      humans, these bonobos do not make errors based on syntactical confusions (e.g.
      confusing semantically unrelated nouns), suggesting that they may not separate
      syntactical and semantic information. These data suggest that apes spontaneously
      create a complex, hierarchical, web of representations when exposed to a symbol
      system.

PMID- 17436025
TI  - Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and
      vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell
      cancer.
AB  - GOALS OF WORK: The aims of this study were to assess the safety and antiemetic
      efficacy of multiple-day dosing of palonosetron plus dexamethasone in patients
      receiving highly emetogenic multiple-day cisplatin-based chemotherapy for germ
      cell tumors. MATERIALS AND METHODS: Forty-one men undergoing 5-day cisplatin
      based chemotherapy for testicular cancer received palonosetron 0.25 mg IV once
      daily 30 min before chemotherapy on days 1, 3, and 5 plus IV dexamethasone 20 mg
      before chemotherapy on days 1 and 2, and 8 mg PO bid on days 6 and 7 and 4 mg bid
      on day 8. Safety and efficacy were assessed in 24-h intervals for 9 days.
      Efficacy endpoints included emesis, intensity of nausea and its interference with
      patient functioning, and rescue antiemetic use. A subset of patients (n = 11) was
      studied for electrocardiograph effects and pharmacokinetic evaluation. MAIN
      RESULTS: This multiple-day antiemetic regimen was safe, with headache and
      constipation the most common treatment-related adverse events, mostly mild.
      Neither adverse events nor electrocardiographic changes appeared to increase in
      frequency, duration, or intensity over time despite a 1.42-fold systemic
      accumulation of palonosetron with repeated doses. The majority of patients had no
      emesis at any time throughout days 1-5 (51%) or days 6-9 (83%), had no moderate
      to-severe nausea, and did not require rescue medication. Most patients reported
      that nausea had no significant effect on daily functioning on days 1-4 (72%) and
      days 5-9 (85%). CONCLUSIONS: Palonosetron on days 1, 3, and 5, along with a
      regimen of dexamethasone, was safe and well tolerated and effectively controlled
      both nausea and emesis in patients undergoing 5-day cisplatin-based chemotherapy
      for testicular cancer.

PMID- 17436027
TI  - The time for cost-effectiveness in the new European Union member states: the
      development and role of health economics and technology assessment in the mirror
      of the Hungarian experience.
AB  - Sophisticated methodology and research centres of health economics and health
      technology assessment were established in the developed countries over the past
      30 years, releasing more and more studies of better and better quality every
      year. A crucial factor in health policy and reimbursement decisions in these
      countries is cost-effectiveness results. Due to methodological diversification,
      results of locally performed health economics studies are constrained in
      international utility. This fact encourages us to set the current goal of
      greatest importance, i.e. to standardise country-specific methods, thereby
      promoting transferability and adaptability of results, being backed by each
      important health care organisation all over Europe. The situation in the new
      member states [European Union (EU)12] is profoundly different compared with EU15.
      In these countries, neither the necessary research institutions nor professionals
      are in place in sufficient numbers; even in most EU12 countries, the importance
      of cost-effectiveness has not yet been realised. The present study focuses mainly
      on the EU12. These countries are absolutely dependent on cost-effectiveness
      results from abroad, and this seems to persist in the long-term. Transferability
      and adaptability of the results of health economics studies carried out elsewhere
      through European collaboration is vital for these countries.

PMID- 17436028
TI  - Imaging in the time of NFD/NSF: do we have to change our routines concerning
      renal insufficiency?
AB  - To date there are potential chronology-based but not conclusive reasons to
      believe that at least some of the gadolinium complexes play a causative role in
      the pathophysiology of nephrogenic systemic fibrosis (NSF) or nephrogenic
      fibrosing dermopathy (NFD). Still, the exact pathogenesis and the risk for
      patients is unclear beside the obvious connection to moderate to severe renal
      insufficiency. So far, MR imaging with Gd-enhancement was regarded as the safest
      imaging modality in these patients--the recent development creates tremendous
      uncertainty in the MR-community. Nevertheless, one should remember that, despite
      the over 200 cases of NSF and about 100 with proven involvement of Gd(3+), the
      vast majority of over 200 million patients exposed to gadolinium since the 1980s
      have tolerated these agents well. Importantly, NSF is a rare disease and does not
      appear to occur in patients without renal impairment. Many patients and
      researchers have undergone MR investigations with Gd exposure in the past. For
      those, it is essential to know about the safety of the agents at normal renal
      function. We can hope that pharmacoepidemiological and preclinical studies will
      allow us to better understand the pathophysiology and role of the various MR
      contrast agents in the near future.

PMID- 17436029
TI  - Epidermal lipoxygenase products of the hepoxilin pathway selectively activate the
      nuclear receptor PPARalpha.
AB  - Arachidonic acid can be transformed into a specific epoxyalcohol product via the
      sequential action of two epidermal lipoxygenases, 12R-LOX and eLOX3. Functional
      impairment of either lipoxygenase gene (ALOX12B or ALOXE3) results in ichthyosis,
      suggesting a role for the common epoxyalcohol product or its metabolites in the
      differentiation of normal human skin. Here we tested the ability of products
      derived from the epidermal LOX pathway to activate the peroxisome proliferator
      activated receptors PPARalpha, gamma, and delta, which have been implicated in
      epidermal differentiation. Using a dual luciferase reporter assay in PC3 cells,
      the 12R-LOX/eLOX3-derived epoxyalcohol, 8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z
      trienoic acid, activated PPARalpha with similar in potency to the known natural
      ligand, 8S-hydroxyeicosatetraenoic acid (8S-HETE) (both at 10 microM
      concentration). In contrast, the PPARgamma and PPARdelta receptor isoforms were
      not activated by the epoxyalcohol. Activation of PPARalpha was also observed
      using the trihydroxy hydrolysis products (trioxilins) of the unstable
      epoxyalcohol. Of the four trioxilins isolated and characterized, the highest
      activation was observed with the isomer that is also formed by enzymatic
      hydrolysis of the epoxyalcohol. Formation of a ligand for the nuclear receptor
      PPARalpha may be one possibility by which 12R-LOX and eLOX3 contribute to
      epidermal differentiation.

PMID- 17436030
TI  - Food insecurity is associated with diabetes mellitus: results from the National
      Health Examination and Nutrition Examination Survey (NHANES) 1999-2002.
AB  - BACKGROUND: Food insecurity refers to limited or uncertain access to food
      resulting from inadequate financial resources. There is a clear association
      between food insecurity and obesity among women, but little is known about the
      relationship between food insecurity and type 2 diabetes. OBJECTIVE: To evaluate
      whether there is an independent association between food insecurity and diabetes.
      DESIGN: Cross-sectional analysis of the nationally representative, population
      based National Health and Nutrition Examination Survey (1999-2002 waves).
      PARTICIPANTS: Four thousand four hundred twenty-three adults > 20 years of age
      with household incomes < or = 300% of the federal poverty level. MEASUREMENTS: We
      categorized respondents as food secure, mildly food insecure, or severely food
      insecure using a well-validated food insecurity scale. Diabetes was determined by
      self-report or a fasting serum glucose > or = 126 mg/dl. RESULTS: Diabetes
      prevalence in the food secure, mildly food insecure, and severely food insecure
      categories was 11.7%, 10.0%, and 16.1%. After adjusting for sociodemographic
      factors and physical activity level, participants with severe food insecurity
      were more likely to have diabetes than those without food insecurity (adjusted
      odds ratio [AOR] 2.1, 95% CI 1.1-4.0, p = .02). This association persisted after
      further adjusting for body mass index (AOR 2.2, 95% CI 1.2-3.9, p = .01).
      CONCLUSIONS: Food insecurity may act as a risk factor for diabetes. Among adults
      with food insecurity, increased consumption of inexpensive food alternatives,
      which are often calorically dense and nutritionally poor, may play a role in this
      relationship. Future work should address how primary care clinicians can most
      effectively assist patients with food insecurity to make healthy dietary changes.

PMID- 17436031
TI  - The positive role of the ecological community in the genomic revolution.
AB  - The exponential increase of genomic and metagenomic data, fueled in part by
      recent advancements in sequencing technology, are greatly expanding our
      understanding of the phylogenetic diversity and metabolic capacity present in the
      environment. Two of the central challenges that bioinformaticians and ecologists
      alike must face are the design of bioinformatic resources that facilitate the
      analysis of genomic and metagenomic data in a comparative context and the
      efficient capture and organization of the plethora of descriptive information
      required to usefully describe these data sets. In this commentary, we review
      three initiatives presented in the "new frontiers" session of the second SCOPE
      meeting on Microbial Environmental Genomics (MicroEnGen-II, Shanghai, June 12-15,
      2006). These are (1) the Integrated Microbial Genomes Resources (IMG), (2) the
      Genomic Standards Consortium (GSC), and (3) the Natural Environment Research
      Council (NERC) Environmental Bioinformatics Centre (NEBC). These integrative
      bioinformatics and data management initiatives underscore the increasingly
      important role ecologists have to play in the genomic (metagenomic) revolution.

PMID- 17436032
TI  - Beneficial effect of partial portal decompression using the inferior mesenteric
      vein for intractable gastroesophageal variceal bleeding in patients with liver
      cirrhosis.
AB  - BACKGROUND: Use of the inferior mesenteric vein (IMV) for partial portal
      decompression has not been recommended as a first-line option for intractable
      gastroesophageal variceal bleeding because of the thin diameter of the vein.
      Although these indications remain relevant, few reports have compared partial
      portal decompression using the IMV with other therapies. We propose that partial
      portal decompression using the IMV is a useful alternative treatment for
      intractable variceal bleeding. METHODS: We performed partial portal decompression
      using the IMV in eight patients with intractable variceal bleeding that had been
      uncontrolled using medical and endoscopic therapies. All patients were classified
      into Child's class B or C. The surgical data, morbidity, and mortality were
      assessed. RESULTS: Mean portal venous pressure significantly decreased from 26.9
      +/- 2.0 mmHg before the surgery to 19.8 +/- 3.9 mmHg after the surgery. The
      operative mortality rate was 0%. The mean duration of hospital stay was 25.5 +/-
      13.3 days. Although one patient experienced recurrent bleeding, shunt patency was
      well maintained in all patients during the follow-up period (mean 28.9 +/- 14.1
      months). Six patients are still alive and well without ascites or hepatic
      encephalopathy. Two of the Child's class C patients who underwent emergency shunt
      died owing to hepatic decompensation. CONCLUSION: Partial portal decompression
      using the IMV can be a safe, effective way to treat intractable variceal bleeding
      in patients with liver cirrhosis. However, use of the shunt procedure may have
      the most survival benefits for cirrhotic patients with preserved liver function.

PMID- 17436033
TI  - Ruptured internal iliac artery aneurysm: staged emergency endovascular treatment
      in the interventional radiology suite.
AB  - Ruptured aneurysms of the internal iliac artery (IIA) are rare and challenging to
      treat surgically. Due to their anatomic location they are difficult to operate on
      and perioperative morbidity is high. An endovascular approach can be helpful. We
      recently treated a patient with a ruptured IIA aneurysm in the interventional
      radiology suite with embolization of the side-branch of the IIA and placement of
      a covered stent in the ipsilateral common and external iliac arteries. A suitable
      stent-graft was not available initially and had to be brought in from elsewhere.
      An angioplasty balloon was temporarily placed across the ostium of the IIA to
      obtain hemostasis. Two hours later, the procedure was finished by placing the
      stent-graft.

PMID- 17436034
TI  - Radiofrequency ablation in combination with embolization in metachronous
      recurrent renal cancer in solitary kidney after contralateral tumor nephrectomy.
AB  - PURPOSE: To evaluate the feasibility and safety of minimally invasive,
      percutaneous techniques in metachronous recurrent renal cell cancers (RCCs) in
      solitary kidneys. METHODS: In 4 patients, recurrent RCC was treated by
      radiofrequency ablation (RFA) (RITA, StarBurst) alone, and in 2 patients by RFA
      in combination with superselective transarterial particle-lipiodol embolization
      using 3 Fr microcatheters. RFA was guided by computed tomography in 5 patients,
      and by magnetic resonance imaging in 1 patient. Mean tumor diameter was 26.7 mm
      (range 10-45 mm). All interventions were technically successful; during follow-up
      1 patient developed recurrent RCC, which was retreated by RFA after embolization.
      RESULTS: No major peri- or postprocedural complications occurred. Changes in
      creatinine (pre- vs. post-intervention, 122 vs. 127 micromol/l) and calculated
      creatinine clearance (pre- vs. post-intervention, 78 vs. 73 ml/min) after
      ablation were minimal. CONCLUSION: In single kidneys, percutaneous, minimally
      invasive techniques are safe and feasible. In large tumors, or where there are
      adjacent critical structures, we prefer a combination of embolization and thermal
      ablation (RFA).

PMID- 17436035
TI  - Evaluation of the effects of temporary covered nitinol stent placement in the
      prostatic urethra: short-term study in the canine model.
AB  - PURPOSE: To evaluate the effect of temporary stent placement on the canine
      prostatic urethra. METHODS: Retrievable PTFE-covered nitinol stents were placed
      in the prostatic urethras of 8 beagle dogs under fluoroscopic guidance.
      Retrograde urethrography was obtained before and after stenting. Retrograde
      urethrography and endoscopy were performed 1 and 2 months after deployment. The
      endoscopic degree of hyperplasia was rated on a scale of 0 to 4 (0 = absence, 4 =
      occlusion). On day 60, stents were removed and urethrography was performed
      immediately before euthanasia. Pathologic analysis was performed to determine the
      degree of glandular atrophy, periurethral fibrosis, and urethral dilation.
      RESULTS: Stent deployment was technically successful in 7 animals, and failed in
      1 dog due to a narrow urethral lumen. Complete migration was seen in 2 animals at
      1 month, and an additional stent was deployed. On day 30, endoscopy showed slight
      hyperplasia (grade 1) in 3 animals. On day 60, moderate hyperplasia (grade 2) was
      evidenced in 4 cases. No impairment of urinary flow was seen during follow-up.
      Retrieval was technically easy to perform, and was successful in all dogs. The
      major histologic findings were chronic inflammatory cell infiltrates; prostate
      glandular atrophy, with a mean value of 1.86 (SD 0.90); periurethral fibrosis,
      with a mean ratio of 29.37 (SD 10.41); and dilatation of the prostatic urethra,
      with a mean ratio of 6.75 (SD 3.22). CONCLUSION: Temporary prostatic stent
      placement in dogs is safe and feasible, causing marked enlargement of the
      prostatic urethral lumen. Retrievable covered stents may therefore be an option
      for bladder outlet obstruction management in men.

PMID- 17436036
TI  - The 20th International Mammalian Genome Conference meeting report.

PMID- 17436038
TI  - Genomic expansion of the Bov-A2 retroposon relating to phylogeny and breed
      management.
AB  - Bov-A2 is a retroposon that is widely distributed among the genomes of ruminants
      (e.g., cow, deer, giraffe, pronghorn, musk deer, and chevrotain). This retroposon
      is composed of two monomers, called Bov-A units, which are joined by a linker
      sequence. The structure and origin of Bov-A2 has been well characterized but a
      genome-level exploration of this retroposon has not been implemented. In this
      study we performed an extensive search for Bov-A2 using all available genome
      sequence data on Bos taurus. We found unique Bov-A2-derived sequences that were
      longer than Bov-A2 due to amplification of three to six Bov-A units arranged in
      tandem. Detailed analysis of these elongated Bov-A2-derived sequences revealed
      that they originated through unequal crossing-over of Bov-A2. We found a large
      number of these elongated Bov-A2-derived sequences in cattle genomes, indicating
      that unequal crossing-over of Bov-A2 occurred very frequently. We found that this
      type of elongation is not observed in wild bovine and is therefore specific to
      the domesticated cattle genome. Furthermore, at specific loci, the number of Bov
      A units was also polymorphic between alleles, implying that the elongation of Bov
      A units might have occurred very recently. For these reasons, we speculate that
      genomic instability in bovine genomes can lead to extensive unequal crossing-over
      of Bov-A2 and levels of polymorphism might be generated in part by repeated
      outbreeding.

PMID- 17436037
TI  - Mouse Phenotype Database Integration Consortium: integration [corrected] of mouse
      phenome data resources.
AB  - Understanding the functions encoded in the mouse genome will be central to an
      understanding of the genetic basis of human disease. To achieve this it will be
      essential to be able to characterize the phenotypic consequences of variation and
      alterations in individual genes. Data on the phenotypes of mouse strains are
      currently held in a number of different forms (detailed descriptions of mouse
      lines, first-line phenotyping data on novel mutations, data on the normal
      features of inbred lines) at many sites worldwide. For the most efficient use of
      these data sets, we have initiated a process to develop standards for the
      description of phenotypes (using ontologies) and file formats for the description
      of phenotyping protocols and phenotype data sets. This process is ongoing and
      needs to be supported by the wider mouse genetics and phenotyping communities to
      succeed. We invite interested parties to contact us as we develop this process
      further.

PMID- 17436039
TI  - Sleep-related breathing disorders in patients with idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic and usually fatal lung disease
      of unknown etiology. The aim of this study was to describe clinical and
      polysomnographic features of sleep-related breathing disorders (SRBD) and to
      identify predictors of obstructive sleep apnea (OSA) in IPF patients. Eight
      hundred fifty-seven patients with IPF were admitted to the Cleveland Clinic from
      2001 to 2005. An all-night polysomnogram (PSG) was performed in 18 of them to
      investigate complaints suggestive of sleep-disordered breathing. OSA was
      confirmed in 11 of the 18 IPF patients with complaints suggestive of sleep apnea,
      while the remain 7 patients had a diagnosis of primary snoring or upper airway
      resistance syndrome (UARS). All patients showed a reduction in sleep efficiency,
      REM sleep, and slow wave sleep. The apnea-hypopnea index (AHI) was positively
      correlated with body mass index (p < 0.0001, r = 0.80). The REM AHI and overall
      AHI were negatively correlated with FEV(1) (p = 0.008, r = -0.59 and p = 0.04, r
      = -0.49, respectively) and FVC percentages (p = 0.03, r = -0.50 and p = 0.08, r =
      -0.42, respectively). Our study is the first describing SRBD in IPF patients. An
      increased BMI and a significant impairment in pulmonary function testing may be
      predictors of OSA in this population. In the absence of effective treatments for
      IPF, the diagnosis and treatment of comorbid SRBD may lead to improvements in
      quality of life.

PMID- 17436041
TI  - What is the chin-down posture? A questionnaire survey of speech language
      pathologists in Japan and the United States.
AB  - The "chin-down" or "chin-tuck" maneuver is a postural technique widely used in
      dysphagia treatment. The posture, however, does not have a precise anatomical
      definition. We studied the current practice of 42 speech-language pathologists
      (SLPs) in Japan and the U.S. with a questionnaire survey regarding the chin-down
      posture. The main findings were that (1) three of five of the pictures were
      selected by respondents both in Japan and in the U.S. as depicting the chin-down
      posture; (2) 23% of Japanese and 58% of the U.S. SLPs made a distinction between
      chin down and chin tuck; and (3) the use of anatomical terminology by SLPs
      differed between the two countries. This study showed that there is poor
      agreement among SLPs about the meaning of the chin-down and chin-tuck postures.
      Developing a precise definition is important because various postures may have
      differing physiologic effects.

PMID- 17436043
TI  - The mini-fellowship concept: a six-week focused training program for minimally
      invasive bariatric surgery.
AB  - OBJECTIVE: To devise a six-week hands-on training program customized to meet the
      needs of practicing general surgeons. The aim of this program is to provide the
      required training experience that will bestow the knowledge and skill necessary
      to implement a successful practice in laparoscopic bariatric surgery. METHODS:
      Ten board-certified/board-eligible practicing general surgeons with no prior
      hands-on or formal training in laparoscopic bariatric surgery. We report on the
      participants training experience and the impact that the program had on their
      subsequent laparoscopic bariatric clinical activity. RESULTS: Ten surgeons
      completed training programs from 9/01 to 3/03. None of the trainees had prior
      experience in laparoscopic bariatric surgery. Program operative experience
      averaged 42 cases (range 29-66). Trainees were integrated into all preoperative
      and postoperative hospital and outpatient care on the service, including
      workshops and seminars. Seven graduates are in practice performing laparoscopic
      bariatric surgery and three are implementing new bariatric programs. The active
      surgeons report performing an average of 101 laparoscopic bariatric procedures
      (range 18-264) over a mean practice period of 10 months (range 4-16) CONCLUSION:
      A six-week focused mini-fellowship with hands-on operative and clinical
      participation enables practicing surgeons to acquire the skill and experience
      necessary to successfully implement a laparoscopic bariatric surgical practice.

PMID- 17436040
TI  - Elevated levels of IL-18 in plasma and skeletal muscle in chronic obstructive
      pulmonary disease.
AB  - The aim of this study was to test the hypothesis that systemic inflammation in
      patients with chronic obstructive pulmonary disease (COPD) is accompanied by
      enhanced interleukin 18 (IL-18) expression in skeletal muscle, which may precede
      muscle weight loss. Twenty patients with moderate to severe COPD [12 women, 66 +/
      9.4 years of age and forced expiratory volume in 1 second (FEV(1)) of 32% +/- 12
      % of predicted value] and 20 healthy age-, gender-, and body mass index (BMI)
      matched controls (10 nonsymptomatic smokers and 10 nonsmokers) were included in
      the study. Plasma levels of IL-18 were elevated in COPD patients (n = 20) versus
      healthy controls (n = 20) (221.2 pg/ml [196.0-294.2 pg/pl] vs. 164.8 pg/ml [144.4
      193.3 pg/pl], p = 0.05) [corrected] and IL-18 was expressed in skeletal muscle,
      with IL-18 mRNA levels being elevated in biopsies from COPD patients (n = 19)
      versus healthy controls (n = 18) (4.3 [2.6-5.9] vs. 2.4 [1.6-3.1], p = 0.05)
      [corrected]. Immunohistochemical evaluation revealed a strong expression of IL-18
      in Type II muscle fibers from COPD patients. Plasma levels and skeletal muscle
      mRNA levels of tumor necrosis factor alpha (TNF-alpha) and IL-6 did not differ
      between the groups. Elevated skeletal muscle expression of IL-18 was found in
      COPD patients with normal body weight, indicating that IL-18 potentially may be
      involved in the pathogenesis of COPD-associated muscle wasting.

PMID- 17436042
TI  - Optimizing laparoscopic task efficiency: the role of camera and monitor
      positions.
AB  - BACKGROUND: Alterations of video monitor and laparoscopic camera position may
      create perceptual distortion of the operative field, possibly leading to
      decreased laparoscopic efficiency. We aimed to determine the influence of
      monitor/camera position on the laparoscopic performance of surgeons of varying
      skill levels. METHODS: Twelve experienced and 12 novice participants performed a
      one-handed task with their dominant hand in a modified laparoscopic trainer.
      Initially, the camera was fixed directly in front of the participant (0 degrees)
      and the monitor location was varied between three positions, to the left of
      midline (120 degrees), directly across from the participant (180 degrees), and to
      the right of the midline (240 degrees). In the second experiment monitor position
      was constant straight across from the participant (180 degrees) while the camera
      position was adjusted between the center position (0 degrees), to the left of
      midline (60 degrees), and to the right of midline (300 degrees). Participants
      completed five trials in each monitor/camera setting. The significance of the
      effects of skill level and combinations of camera and monitor angle were
      evaluated by analysis of variance (ANOVA) for repeated measures using restricted
      maximum likelihood estimation. RESULTS: Experienced surgeons completed the task
      significantly faster at all monitor/camera positions. The best performance in
      both groups was observed when the monitor and camera were located at 180 degrees
      and 0 degrees, respectively. Monitor positioning to the right of midline (240
      degrees) resulted in significantly worse performance compared to 180 degrees for
      both experienced and novice surgeons. Compared to 0 degrees (center), camera
      position to the left or the right resulted in significantly prolonged task times
      for both groups. Novice subjects also demonstrated a significantly lower ability
      to adjust to suboptimal camera/monitor positions. CONCLUSION: Experienced
      subjects demonstrated superior performance under all study conditions. Optimally,
      the camera should be directly in front and the monitor should be directly across
      from a surgeon. Alternatively, the monitor/camera could be placed opposite to the
      surgeon's non-dominant hand. The suboptimal camera/monitor conditions are
      especially difficult to overcome for inexperienced subjects. Monitor and camera
      positioning must be emphasized to ensure optimal laparoscopic performance.

PMID- 17436044
TI  - A new technique for intestinal isoperistaltic anastomosis utilizing a linear
      stapler for enlargement after anastomosis performed with a circular stapler.
AB  - BACKGROUND: The high incidence of anastomotic stenosis after gastrointestinal
      surgery using circular staplers is a major problem. In response, we have
      developed a new technique that uses a linear stapler to enlarge an anastomotic
      opening made using a circular stapler. METHODS: Anastomoses were created by the
      new technique or by the conventional approach using a circular stapler in pig
      small intestine. The method was also applied in treatment of a colon cancer
      patient. RESULTS: The area of the anastomotic opening obtained with the new
      technique was more than 3 times that in the control (p < 0.001), with no
      significant difference between the methods in a leak test. Follow-up of the
      patient undergoing surgery with this approach revealed an uneventful course with
      a widely patent anastomosis confirmed after 3 months. CONCLUSIONS: This procedure
      provides a larger anastomotic opening than conventional anastomosis with circular
      staplers, without impairing the integrity of the anastomosis.

PMID- 17436046
TI  - Novel antifoulants: inhibition of larval attachment by proteases.
AB  - We investigated the effect of commercially available enzymes (alpha-amylase,
      alpha-galactosidase, papain, trypsin, and lipase) as well as proteases from deep
      sea bacteria on the larval attachment of the bryozoan Bugula neritina L. The 50%
      effective concentrations (EC(50)) of the commercial proteases were 10 times lower
      than those of other enzymes. Crude proteases from six deep-sea Pseudoalteromonas
      species significantly decreased larval attachment at concentrations of 0.03 to 1
      mIU ml(-1). The EC(50) of the pure protease from the bacterium Pseudoalteromonas
      issachenkonii UST041101-043 was close to 1 ng ml(-1) (0.1 mIU ml(-1)). The
      protease and trypsin individually incorporated in a water-soluble paint matrix
      inhibited biofouling in a field experiment. There are certain correlations
      between production of proteases by bacterial films and inhibition of larval
      attachment. None of the bacteria with biofilms that induced attachment of B.
      neritina produced proteolytic enzymes, whereas most of the bacteria that formed
      inhibitive biofilms produced proteases. Our investigation demonstrated the
      potential use of proteolytic enzymes for antifouling defense.

PMID- 17436047
TI  - Radon-domain detection of the nipple and the pectoral muscle in mammograms.
AB  - In this paper, methods are presented for automatic detection of the nipple and
      the pectoral muscle edge in mammograms via image processing in the Radon domain.
      Radon-domain information was used for the detection of straight-line candidates
      with high gradient. The longest straight-line candidate was used to identify the
      pectoral muscle edge. The nipple was detected as the convergence point of breast
      tissue components, indicated by the largest response in the Radon domain.
      Percentages of false-positive (FP) and false-negative (FN) areas were determined
      by comparing the areas of the pectoral muscle regions delimited manually by a
      radiologist and by the proposed method applied to 540 mediolateral-oblique (MLO)
      mammographic images. The average FP and FN were 8.99% and 9.13%, respectively. In
      the detection of the nipple, an average error of 7.4 mm was obtained with
      reference to the nipple as identified by a radiologist on 1,080 mammographic
      images (540 MLO and 540 craniocaudal views).

PMID- 17436045
TI  - The use of autologous platelet-leukocyte gels to enhance the healing process in
      surgery, a review.
AB  - BACKGROUND: The therapeutic use of autologously prepared, platelet-leukocyte
      enriched gel (PLG) is a relatively new technology for the stimulation and
      acceleration of soft tissue and bone healing. The effectiveness of this procedure
      lies in the delivery of a wide range of platelet growth factors mimicking the
      physiologic wound healing and reparative tissue processes. Despite an increase in
      PLG applications, the structures and kinetics of this autogenously derived
      biologic material have not been observed. METHODS: A review of the most recent
      literature was performed to evaluate the use of PLG in various surgical
      disciplines. RESULTS: The review showed that the application of PLG has been
      extended to various surgical disciplines including orthopedics, cardiac surgery,
      plastic and maxillofacial surgery, and recently also endoscopic surgery.
      CONCLUSION: This review demonstrates the usefulness of PLG in a wide range of
      clinical applications for improvement of healing after surgical procedures.

PMID- 17436048
TI  - Epithelial molecular markers in the peripheral blood of patients with colorectal
      cancer.
AB  - Despite the modest improvements in patient survival from colorectal cancer in the
      last few decades, the overall five-year survival rate remains at 40 to 45
      percent. Surgical resection is the mainstay of treatment for colorectal cancer;
      however, nearly one-half of all patients who undergo a potentially curative
      resection will relapse because of undetected micrometastasis. The fact that the
      overall survival rate remains poor strongly suggests that the dissemination of
      these cells occurs early in the disease process and emphasizes the need for
      finding feasible diagnostic methods with sufficient sensitivity and specificity.
      The most commonly used technique for the detection of nucleic acid material of
      disseminated tumor cells is the polymerase chain reaction. We critically review
      the literature on DNA and messenger ribonucleic acid molecular markers that have
      been used for the detection of circulating tumor cells in the peripheral blood of
      patients with colorectal cancer and other solid tumors as appropriate for
      comparison. The cytokeratins, particularly cytokeratin 19 and cytokeratin 20, are
      the most investigated prognostic markers, but even for these questions remain
      about their clinical value, and hence most recent studies are utilizing a
      combination of factors. There is an urgent need for standardized isolation and
      analysis techniques to be adopted thus allowing large-scale, appropriately
      controlled, multicenter trials to be undertaken on the most promising candidate
      markers.

PMID- 17436049
TI  - A composite adenoendocrine carcinoma of the stomach arising from a neuroendocrine
      tumor.
AB  - Gastric neuroendocrine tumors (carcinoids) are relatively uncommon neoplasms.
      Some 70 to 80% of these lesions occur in patients with autoimmune body gastritis.
      This disorder, however, is also a risk factor for the development of conventional
      gastric adenocarcinomas. We report a case of a patient with autoimmune body
      gastritis and a well-differentiated neuroendocrine tumor of the stomach, which
      was removed with endoscopic full-thickness resection in sano upon signs of
      invasive growth several years after its first diagnosis. Histological examination
      surprisingly showed a composite glandular-endocrine gastric carcinoma. We discuss
      the histopathological genesis of the tumor and provide evidence that endoscopic
      full-thickness resection might be an oncologically appropriate minimally invasive
      treatment for such gastric lesions.

PMID- 17436050
TI  - Hyperbilirubinemia in appendicitis: a new predictor of perforation.
AB  - This study examines the relationship between hyperbilirubinemia and appendicitis.
      It was hypothesized that an association exists between the presence of
      appendiceal perforation and hyperbilirubinemia. Patients with liver function
      tests on admission and pathologically confirmed appendicitis were included in the
      study. Age, duration of symptoms, temperature, white blood cell counts, systemic
      inflammatory response score, and bilirubin levels were independent variables in a
      logistic regression analysis assessing factors predicting the presence or absence
      of appendiceal gangrene/perforation. Elevated total bilirubin levels (>1 mg/dl)
      were found in 59 (38%) of 157 patients. Patients with gangrene/perforation were
      significantly (p = 0.004) more likely to have hyperbilirubinemia than those with
      acute suppurative appendicitis. No statistical differences were observed for any
      of the other variables. On logistic regression the only significant relationship
      between the presence or absence of appendiceal gangrene and perforation was the
      presence of hyperbilirubinemia (p = 0.031, 95% confidence interval 1.11-7.6). The
      odds of appendiceal perforation are three times higher (odds ratio 2.96) for
      patients with hyperbilirubinemia compared to those with normal bilirubin levels.
      Hyperbilirubinemia is frequently associated with appendicitis. Elevated bilirubin
      levels have a predictive potential for the diagnosis of appendiceal perforation.

PMID- 17436051
TI  - Normal lower esophageal sphincter pressure and length does not impact outcome
      after laparoscopic Nissen fundoplication.
AB  - Intuitively, a manometrically normal lower esophageal sphincter (LES) will
      promote dysphagia after laparoscopic Nissen fundoplication. This study was
      undertaken to compare outcomes after laparoscopic Nissen fundoplication for
      patients who had normal and manometrically inadequate LES preoperatively. Before
      fundoplication, the length and resting pressures of LES were determined
      manometrically in 59 patients with documented gastroesophageal reflux disease
      (GERD). Twenty-nine patients had a manometrically normal LES, with resting
      pressures >10 mm Hg and length >2 cm. Thirty patients had resting pressures of <
      or =10 mm Hg and length of < or =2 cm. Before and after fundoplication, patients
      graded the frequency and severity of symptoms of GERD utilizing a Likert scale (0
      = never/not bothersome to 10 = always/very bothersome). DeMeester scores and
      symptom scores before and after fundoplication were compared. Before
      fundoplication, the manometric character of the LES did not impact the elevation
      of DeMeester scores or the frequency/severity of reflux symptoms. All symptoms
      improved significantly with fundoplication independent of LES pressure/length.
      Prefundoplication, manometric character of the LES did not impact the frequency
      or severity of reflux symptoms after fundoplication. Preoperative manometric
      character of the LES does not impact the presentation of GERD or the outcome
      after fundoplication. Symptoms globally and significantly improve after
      fundoplication, independent of manometric LES character. Normal LES manometry
      does not impact outcome and, specifically, does not promote dysphagia, after
      laparoscopic Nissen fundoplication.

PMID- 17436052
TI  - A novel biodegradable biliary stent in the normal duct hepaticojejunal
      anastomosis: an 18-month follow-up in a large animal model.
AB  - Creating a well-functioning hepaticojejunostomy (HJ) anastomosis with nondilated
      bile ducts remains a challenge. Our aim was to study the use in a large animal
      model of a novel, braided polylactide barium sulfate biodegradable biliary stent
      (BDBS) without external connection and with no need for later removal. Fifty
      swine were randomly operated on for Roux-Y HJ with or without BDBS in the
      anastomosis, and followed up (dynamic biligraphy, x-ray, serum determinations,
      anastomosis inner diameter, and histology) for 1.5, 3, 6, 12, and 18 months.
      During the follow-up, one nonstented animal died because of anastomotic leakage.
      In x-ray BDBS was seen in place until 1.5 months in all of the stented animals.
      In the nonstented animals HJ anastomosis inner diameter was decreased at 18
      months [6.3 (5.0-7.0) mm vs 7.4 (7.0-9.0) mm, p = 0.05] and liver clearance
      reduced at 12 and 18 months compared to stented animals. Serum liver values and
      liver and bile duct histology did not differ between the groups. We conclude that
      this novel BDBS is easy to insert into the HJ anastomosis with nondilated ducts.
      It is nontoxic, dissolves safely, and may be associated with a larger and better
      draining anastomosis at 18-month follow-up. These results encourage us to proceed
      to clinical studies.

PMID- 17436053
TI  - Acute pseudoseptic arthritis after viscosupplementation of the knee: a case
      report.
AB  - Intra-articular injections of hyaluronan are generally well tolerated; the most
      common adverse event associated with their use is an inflammatory reaction or a
      flare at the injection site. Naturally derived sodium hyaluronates have not been
      associated with pseudosepsis; we describe a case of severe arthritis mimicking
      acute septic arthritis after naturally hyaluronan. A 70-year-old woman had a
      medial femorotibial and patellofemoral compartment knee osteoarthritis.
      Hyaluronic acid injection was indicated because of the persistence of a pain
      while walking and restricted ability to walk 100 m, as well as the installation
      of a flessum. She was admitted for an evaluation of a joint effusion occurring
      within 48 h after the first hyaluronic acid intra-articular injection (first
      course), with no fever or chills. Joint fluid was found to be cloudy and
      contained 24,000 cells per mm(3). A knee aspiration was performed to evaluate the
      possibility of a joint infection. The examination of synovial fluid under phase
      contrast and polarizing microscopes showed no crystals, and culture on standard
      media was negative. Acute septic arthritis was considered to be the most likely
      diagnosis, and probabilistic antibiotic therapy was started. The result of the
      bacteriological examinations also returned negative. The absence of general
      signs, particularly fever and chills, with fast effusion regression in less than
      4 days did not plead in favor of a septic origin. In front of this beam of
      arguments, antibiotic therapy was stopped after 4 days. The nonsteroidal anti
      inflammatory drug (Nimesulide) was given. The clinical and laboratory test
      abnormalities were normalized within 2 weeks. Our case has the particularity to
      occur after using Curavisc, which is known as producing no allergenic reactions.
      Moreover, the described reaction occurred with the very first infiltration within
      the very first course.

PMID- 17436055
TI  - Blood pressure, hypertension and mortality from circulatory disease in men and
      women who survived the siege of Leningrad.
AB  - The population of Leningrad suffered from severe starvation, cold and
      psychological stress during the siege in 1941-1944. We investigated long-term
      effects of the siege on cardiovascular risk factors and mortality in surviving
      men and women. 3905 men born 1916-1935 and 1729 women born 1910-1940, resident in
      St Petersburg (formerly Leningrad) between 1975 and 1982, of whom a third
      experienced the siege as children, adolescents or young adults, were examined for
      cardiovascular risk factors in 1975-1977 and 1980-1982 respectively and followed
      till end 2005. Effects of siege exposure on blood pressure, lipids, body size,
      and mortality were studied in multivariate analysis stratified by gender and
      period of birth, adjusted for age, smoking, alcohol and social characteristics.
      Women who were 6-8 years-old and men who were 9-15 years-old at the peak of
      starvation had higher systolic blood pressure compared to unexposed subjects born
      during the same period of birth (fully adjusted difference 8.8, 95% CI: 0.1-17.5
      mm Hg in women and 2.9, 95% CI: 0.7-5.0 mm Hg in men). Mean height of women who
      were exposed to siege as children appeared to be greater than that of unexposed
      women. Higher mortality from ischaemic heart disease and cerebrovascular disease
      was noted in men exposed at age 6-8 and 9-15, respectively. The experience of
      severe stress and starvation in childhood and puberty may have long-term effects
      on systolic blood pressure and circulatory disease in surviving men and women
      with potential gender differences in the effect of siege experienced at pre
      pubertal age.

PMID- 17436056
TI  - Can ethical reasoning contribute to better epidemiology? A case study in research
      on racial health disparities.
AB  - A common belief among epidemiologists and other scientists is that they ought not
      engage in ethical evaluation or endorse any particular ethical, political, or
      social values while involved in scientific reasoning. Such values are irrelevant
      to collecting and interpreting data and can only lead to bias. This view is also
      reflected in scientists' education. The authors argue that ethical values are
      crucial to conducting much epidemiological research. Focusing on epidemiological
      research on racial health disparities, they show that value judgments are
      inescapable when performing such research. Values are implicit in the framing of
      research questions, the identification of the problem, and the choices of design
      and methodology. By making value judgments explicit, scientists will be more
      likely to pay attention to them and thus assess them in critical ways. Finally,
      the implications that this has for scientific training are discussed. Scientific
      training should prepare scientists to engage in ethical reasoning not only
      because it will make them more responsible human beings, but also because it will
      make them better scientists.

PMID- 17436057
TI  - Role of tropomyosin isoforms in the calcium sensitivity of striated muscle thin
      filaments.
AB  - We have expressed alpha & beta isoforms of mammalian striated muscle tropomyosin
      (Tm) and alpha-Tm carrying the D175N or E180G cardiomyopathy mutations. In each
      case the Tm carries an Ala-Ser N-terminal extension to mimic the acetylation of
      the native Tm. We show that these Ala-Ser modified proteins are good analogues of
      the native Tm in the assays used here. We go on to use an in vitro kinetic
      approach to define the assembly of actin filaments with the Tm isoforms with
      either a cardiac or a skeletal muscle troponin (cTn, skTn). With skTn the calcium
      sensitivity of the actin filament is the same for alpha & beta-Tm and there is
      little change with the mutant Tms. For cTn switching from alpha to beta-Tm causes
      an increase of calcium sensitivity of 0.2 pCa units. D175N is very similar to the
      wild type alpha-Tm and E180G shows a small increase in calcium sensitivity of
      about 0.1 pCa unit. The formation of the switched-off blocked-state of the actin
      filament is independent of the Tm isoform but does differ for cardiac versus
      skeletal Tn. The in vitro assays developed here provide a novel, simple and
      efficient method for assaying the behaviour of expressed thin filament proteins.

PMID- 17436058
TI  - Repeated bout effect on the cytoskeletal proteins titin, desmin, and dystrophin
      in rat skeletal muscle.
AB  - The aim of this study was to evaluate the effect of repeated bouts of exercise on
      the cytoskeletal proteins titin, desmin, and dystrophin. Rats were made to run
      downhill for 90 min 1 or 5 times separated by 14 days. Samples were taken from
      quadriceps femoris muscle 3, 48, 96 h and 50 days after the last exercise session
      and detected by quantitative PCR, histochemical stainings, and western blot
      analyses. Histopathological changes in titin, desmin, and dystophin stainings, an
      increase in beta-glucuronidase activity (a quantitative indicator of muscle
      damage), a significant decrease in the relative content of dystrophin, and
      intramyocellular Evans blue staining (signs of changes in sarcolemmal
      permeability) observed after one exercise session were attenuated after 5
      exercise sessions. Titin mRNA level was not increased after the initial exercise
      session but was increased after the fifth session. Desmin and dystrophin mRNA
      levels were increased after the first and fifth sessions with desmin showing a
      smaller increase after the fifth session compared to the first session. Prior
      exercise induces adaptation that protects the sarcolemma as well as
      subsarcolemmal, intermediate filament, and sarcomeric proteins against
      disruption. Changes in mRNA levels of titin, desmin, and dystophin after an acute
      exercise session obviously reflect the need of these proteins in the repair
      process following damage. After five sessions increase in mRNA of studied
      proteins suggest a strong involvement in continuing adaptation to the increased
      exercise.

PMID- 17436061
TI  - A case of ureteral triplication associated with ureteropelvic junction
      obstruction.
AB  - Ureteral triplication is one of the rarest malformations of the upper urinary
      tract. The association of ureteral triplication and obstruction is even rarer. We
      report a case of ureteral triplication associated with hydronephrosis due to
      ureteropelvic junction (UPJ) obstruction at the middle pole ureter. To our
      knowledge, such a malformation has not been described previously.

PMID- 17436059
TI  - Production of vaccines and therapeutic antibodies for veterinary applications in
      transgenic plants: an overview.
AB  - During the past two decades, antibodies, antibody derivatives and vaccines have
      been developed for therapeutic and diagnostic applications in human and
      veterinary medicine. Numerous species of dicot and monocot plants have been
      genetically modified to produce antibodies or vaccines, and a number of diverse
      transformation methods and strategies to enhance the accumulation of the
      pharmaceutical proteins are now available. Veterinary applications are the
      specific focus of this article, in particular for pathogenic viruses, bacteria
      and eukaryotic parasites. We focus on the advantages and remaining challenges of
      plant-based therapeutic proteins for veterinary applications with emphasis on
      expression platforms, technologies and economic considerations.

PMID- 17436062
TI  - Tea polyphenols inhibit rat vascular smooth muscle cell adhesion and migration on
      collagen and laminin via interference with cell-ECM interaction.
AB  - Occlusive lesions of atherosclerosis are the consequence of focal accumulation
      within the innermost layer of the artery of leukocytes from the circulation and
      smooth muscle cells (SMCs) from the underlying media. Tea polyphenol especially (
      )-Epigallocatechin-3-gallate (EGCG) has been shown to have cardiovascular
      protective effect. However, the effects of other catechins such as (+)-catechin,
      and (-)-epicatechin-3-gallate (ECG) on SMC's functions have not been fully
      understood. In the present study, we investigate the effects of tea catechins on
      SMC adhesion and migration. Our results indicate that EGCG and ECG but not (+)
      catechin were able to inhibit SMC adhesion on collagen and laminin, two abundant
      extracellular matrix (ECM) proteins expressed in physiological and pathological
      conditions. Further analyses indicate that EGCG could bind laminin more than
      collagen. Moreover, EGCG could inhibit SMC adhesion to integrin beta1 Ab and
      affect SMC's beta1 integrin expression, suggesting it affects SMC's cellular
      components. In migration experiment, laminin- and PDGF-BB-induced SMC migration
      were both inhibited by EGCG in a dose-dependent manner. Taken together, the data
      presented here provide evidence showing that among these tea catechins, EGCG and
      ECG are relatively effective inhibitors on SMC-ECM interaction and their action
      mechanisms are through interference with SMC's integrin beta1 receptor and
      binding to ECM proteins.

PMID- 17436060
TI  - Biosafety and risk assessment framework for selectable marker genes in transgenic
      crop plants: a case of the science not supporting the politics.
AB  - Selectable marker gene systems are vital for the development of transgenic crops.
      Since the creation of the first transgenic plants in the early 1980s and their
      subsequent commercialization worldwide over almost an entire decade, antibiotic
      and herbicide resistance selectable marker gene systems have been an integral
      feature of plant genetic modification. Without them, creating transgenic crops is
      not feasible on purely economic and practical terms. These systems allow the
      relatively straightforward identification and selection of plants that have
      stably incorporated not only the marker genes but also genes of interest, for
      example herbicide tolerance and pest resistance. Bacterial antibiotic resistance
      genes are also crucial in molecular biology manipulations in the laboratory. An
      unprecedented debate has accompanied the development and commercialization of
      transgenic crops. Divergent policies and their implementation in the European
      Union on one hand and the rest of the world on the other (industrialized and
      developing countries alike), have resulted in disputes with serious consequences
      on agricultural policy, world trade and food security. A lot of research effort
      has been directed towards the development of marker-free transformation or
      systems to remove selectable markers. Such research has been in a large part
      motivated by perceived problems with antibiotic resistance selectable markers;
      however, it is not justified from a safety point of view. The aim of this review
      is to discuss in some detail the currently available scientific evidence that
      overwhelmingly argues for the safety of these marker gene systems. Our
      conclusion, supported by numerous studies, most of which are commissioned by some
      of the very parties that have taken a position against the use of antibiotic
      selectable marker gene systems, is that there is no scientific basis to argue
      against the use and presence of selectable marker genes as a class in transgenic
      plants.

PMID- 17436063
TI  - Enolase and arrestin are novel nonmyelin autoantigens in multiple sclerosis.
AB  - INTRODUCTION: Although myelin autoimmunity is known to be a major factor in the
      pathogenesis of multiple sclerosis (MS), the role of nonmyelin antigens is less
      clear. Given the complexity of this disease, it is possible that autoimmunity
      against nonmyelin antigens also has a pathogenic role. Autoantibodies against
      enolase and arrestin have previously been reported in MS patients. The T-cell
      response to these antigens, however, has not been established. METHODS: Thirty
      five patients with MS were recruited, along with thirty-five healthy controls. T
      cell proliferative responses against non-neuronal enolase, neuron-specific
      enolase (NSE), retinal arrestin, beta-arrestin, and myelin basic protein were
      determined. RESULTS: MS patients had a greater prevalence of positive T-cell
      proliferative responses to NSE, retinal arrestin, and beta-arrestin than healthy
      controls (p<0.0001). The proliferative response against NSE, retinal arrestin,
      and beta-arrestin correlated with the response against myelin basic protein (p <
      or = 0.004). Furthermore, the proliferative response against retinal arrestin was
      correlated to beta-arrestin (p<0.0001), whereas there was no such correlation
      between non-neuronal enolase and NSE (p = 0.23). DISCUSSION: There is
      accumulating evidence to suggest that the pathogenesis of MS involves more than
      just myelin autoimmunity/destruction. Autoimmunity against nonmyelin antigens may
      be a component of this myriad of immunopathological events. NSE, retinal
      arrestin, and beta-arrestin are novel nonmyelin autoantigens that deserve further
      investigation in this respect. Autoimmunity against these antigens may be linked
      to neurodegeneration, defective remyelination, and predisposition to uveitis in
      multiple sclerosis. Further investigation of the role of these antigens in MS is
      warranted.

PMID- 17436064
TI  - Mitochondrial dysfunction in platelets and hippocampi of senescence-accelerated
      mice.
AB  - Senescence-accelerated mice (SAM) strains are useful models to understand the
      mechanisms of age-dependent degeneration. In this study, measurements of the
      mitochondrial membrane potential (Deltapsi(m)) of platelets and the Adenosine
      5(')-triphosphate (ATP) content of hippocampi and platelets were made, and
      platelet mitochondria were observed in SAMP8 (faster aging mice) and SAMR1 (aging
      resistant control mice) at 2, 6 and 9 months of age. In addition, an Abeta
      induced (Amyloid beta-protein) damage model of platelets was established. After
      the addition of Abeta, the Deltapsi(m) of platelets of SAMP8 at 1 and 6 months of
      age were measured. We found that platelet Deltapsi(m), and hippocampal and
      platelet ATP content of SAMP8 mice decreased at a relatively early age compared
      with SAMR1. The platelets of 6 month-old SAMP8 showed a tolerance to Abeta
      induced damages. These results suggest that mitochondrial dysfunction might be
      one of the mechanisms leading to age-associated degeneration in SAMP mice at an
      early age and the platelets could serve as a biomarker for detection of
      mitochondrial function and age related disease.

PMID- 17436065
TI  - Interaction of cationic meso-porphyrins with liposomes, mitochondria and
      erythrocytes.
AB  - Two series of cationic porphyrins meso-(3N-methylpyridinium)phenylporphyrin (3P1,
      3P2c, 3P2t, 3P3 and 3P4) and meso-(4N-methylpyridinium)phenylporphyrin (4P1,
      4P2c, 4P2t, 4P3 and 4P4) were studied to obtain a comprehensive understanding of
      factors that influence the binding of cationic porphyrins to liposomes and
      mitochondria, as well as their photodynamic efficiencies in erythrocytes. Binding
      and photodynamic efficiency were found to be inversely proportional to the number
      of positively charged groups and directly proportional to n-octanol/water
      partition coefficients (log P(OW)), except for the cis molecules 3P2c and 4P2c.
      In the cis molecules, binding and photodynamic efficiency were much higher than
      expected, indicating that specific interactions not accounted by log P(OW)
      enhance photodynamic efficiency. The effect of mitochondrial transmembrane
      electrochemical potentials on cationic porphyrin binding constants was estimated
      to be as large as 15%, and may be useful to selectively target this organelle
      when promoting photodynamic therapy to induce apoptosis.

PMID- 17436066
TI  - Resonance Raman spectra of the FMN of the bovine heart NADH: ubiquinone
      oxidoreductase, the largest membrane protein in the mitochondrial respiratory
      system.
AB  - The resonance Raman spectra of FMN of the bovine heart NADH: ubiquinone
      oxidoreductase with the molecular mass of approximately one million dalton were
      determined by using highly improved enzyme preparation and resonance Raman
      apparatus. The band positions and the H(2)O/D(2)O exchange effect suggest that
      the N(3)-H group in the ring III of the isoalloxazine moiety is buried inside the
      protein to increase the vibrational coupling to the C(2)-N(3)-C(4) stretching
      mode and that the ring I is exposed to the aqueous phase.

PMID- 17436067
TI  - Threshold fatigue and information transfer.
AB  - Neurons in vivo must process sensory information in the presence of significant
      noise. It is thus plausible to assume that neural systems have developed
      mechanisms to reduce this noise. Theoretical studies have shown that threshold
      fatigue (i.e. cumulative increases in the threshold during repetitive firing)
      could lead to noise reduction at certain frequencies bands and thus improved
      signal transmission as well as noise increases and decreased signal transmission
      at other frequencies: a phenomenon called noise shaping. There is, however, no
      experimental evidence that threshold fatigue actually occurs and, if so, that it
      will actually lead to noise shaping. We analyzed action potential threshold
      variability in intracellular recordings in vivo from pyramidal neurons in weakly
      electric fish and found experimental evidence for threshold fatigue: an increase
      in instantaneous firing rate was on average accompanied by an increase in action
      potential threshold. We show that, with a minor modification, the standard
      Hodgkin-Huxley model can reproduce this phenomenon. We next compared the
      performance of models with and without threshold fatigue. Our results show that
      threshold fatigue will lead to a more regular spike train as well as robustness
      to intrinsic noise via noise shaping. We finally show that the increased/reduced
      noise levels due to threshold fatigue correspond to decreased/increased
      information transmission at different frequencies.

PMID- 17436068
TI  - How do individuals with autism plan their movements?
AB  - Two experiments investigated how persons with and without autism plan manual
      aiming movements when advance information is direct and when strategic planning
      is required. In Experiment 1 advance information about hand, direction, and/or
      movement amplitude was manipulated. Reaction times suggested both groups adopted
      a hierarchical pattern of movement planning. In Experiment 2, participants
      performed aiming movements to one of two targets that were the same or different
      size. Participants without autism varied the starting location in anticipation of
      specific target stimuli whereas participants with autism consistently selected
      the midpoint. Overall, individuals with autism used advance information to plan
      their movements when this information was direct. However, their performance
      became stereotyped when strategies were self-generated.

PMID- 17436070
TI  - Sequence analysis of the partial spike glycoprotein gene of porcine epidemic
      diarrhea viruses isolated in Korea.
AB  - Porcine epidemic diarrhea virus (PEDV) causes a devastating enteric disease with
      acute diarrhea, dehydration and significant mortality in swine, thereby incurring
      heavy economic losses in Korea. Spike (S) glycoprotein has been suggested as an
      important determinant for PEDV biological properties. In this study, the
      nucleotide and deduced amino acid sequences of the partial S glycoprotein genes
      of Korean PEDV isolates, including epitope region that is capable of inducing
      PEDV-neutralizing antibodies, were determined. The partial S glycoprotein genes
      were amplified by RT-PCR, cloned, sequenced, and compared with each other as well
      as with reference PEDV strains. By phylogenetic analysis, the Korean PEDV
      isolates were divided into three groups (G1, G2, G3), which had three subgroups
      (G1-1, G1-2, G1-3). Group1 (G1) Korean PEDV isolates were highly homologous to
      CV777, Br1/87, JS-2004-2, KPED-9, P-5V, SM98-1, parent DR13, and attenuated DR13,
      group2 (G2) Korean PEDV isolates were highly homologous to Spk1, and group3 (G3)
      was Chinju99 at the nucleotide and deduced amino acid sequence levels. In
      addition, the G1 Korean PEDV isolates didn't had several specific nucleotides and
      amino acids which were found in the G2 and G3 Korean PEDV isolates, and
      especially the G1-1 Korean PEDV isolates had specific nucleotides and amino acids
      which were not found in the G1-2, G1-3, G2, and G3 Korean PEDV isolates. It was
      suggested that many Korean PEDV isolates are closely related to the G1 including
      CV777, Br1/87, JS-2004-2, KPED-9, P-5 V, SM98-1, parent DR13, and attenuated DR13
      rather than to the G2 and G3 including Spk1 and Chinju99, and notably more
      prevalent PEDVs isolated in Korea are especially close to the Chinese PEDV strain
      JS-2004-2 rather than Korean PEDV strains Spk1, Chinju99, KPED-9, SM98-1, parent
      DR13, and attenuated DR13.

PMID- 17436071
TI  - Prospero mutants induce precocious sexual behavior in Drosophila males.
AB  - Brain maturation, a developmental process influenced by both endogenous and
      environmental factors, can affect sexual behavior. In vertebrates and
      invertebrates, sexual maturation is under the influence of hormones and
      neuromodulators, but the role of developmental genes in this process is still
      poorly understood. We report that prospero (pros), a gene crucial for nervous
      system development, can change the age of onset of sexual behavior in Drosophila
      melanogaster males: adult males carrying a single copy of several pros mutations
      court females and mate at a younger age than control males. However, these pros
      mutations had no effect on female sexual receptivity and did not alter other male
      phenotypes related to mating behavior. The Pros protein was detected in several
      brain and sensory structures of immature adult males, some of which are normally
      involved in the regulation of male specific behaviors. Our data suggest that the
      altered pros expression affects the age of onset of male mating behavior.

PMID- 17436072
TI  - Implementation of HIV prevention interventions with people living with HIV/AIDS
      in clinical settings: challenges and lessons learned.
AB  - Integrating HIV prevention into the clinical care of people living with HIV has
      emerged as a priority in the US As part of a cross-site evaluation this study
      examined the processes by which 15 clinic-based projects implemented
      interventions funded under the Health Resources and Services Administration's
      (HRSA) HIV Prevention with Positives (PwP) in Clinical Settings Initiative. We
      conducted 61 in-depth interviews with researchers and interventionists across the
      15 projects. Intervention implementation was feasible assuming several key
      components were in place: (1) internal leadership to overcome resistance and
      foster interest and motivation among clinical providers and staff; (2) adequate
      attention to creating seamless flow between clinic practice and intervention; and
      (3) ongoing training that met clinician and staff needs as prevention
      interventions become a regular part of care. Interventions well matched to the
      clinical environment and the patient populations were feasible and acceptable to
      health care providers, prevention interventionists, and clinic staff.

PMID- 17436073
TI  - Assessing representativeness of sampling methods for reaching men who have sex
      with men: a direct comparison of results obtained from convenience and
      probability samples.
AB  - Convenience samples are used to determine HIV-related behaviors among men who
      have sex with men (MSM) without measuring the extent to which the results are
      representative of the broader MSM population. We compared results from a cross
      sectional survey of MSM recruited from gay bars between June and October 2001 to
      a random digit dial telephone survey conducted between June 2002 and January
      2003. The men in the probability sample were older, better educated, and had
      higher incomes than men in the convenience sample, the convenience sample
      enrolled more employed men and men of color. Substance use around the time of sex
      was higher in the convenience sample but other sexual behaviors were similar. HIV
      testing was common among men in both samples. Periodic validation, through
      comparison of data collected by different sampling methods, may be useful when
      relying on survey data for program and policy development.

PMID- 17436074
TI  - Coping with HIV treatment side effects: conceptualization, measurement, and
      linkages.
AB  - Side effects from HIV treatments impact quality of life (QOL) and adherence to
      care, and influence decisions about health care. The purposes of this study are
      to describe the development of a measure of coping with HIV treatment side
      effects, the SECope, and to provide support for the reliability and validity of
      the measure. Based in Stress and Coping Theory, the 20-item measure assesses
      strategies for coping with HIV treatment side effects, and includes scales of
      Positive Emotion Focused Coping, Social Support Seeking, Nonadherence,
      Information Seeking, and Taking Side Effect Medications. The factor structure was
      supported by exploratory and confirmatory factor analyses with two samples of
      HIV+ individuals on treatment (Ns = 173 and 233). The SECope has demonstrated
      reliability (internal consistency and test-retest), and its validity is supported
      through construct and criterion-referenced analyses. Nonadherence as a strategy
      for coping with side effects was associated with poorer provider relations, lower
      treatment knowledge, and higher beliefs of treatment effectiveness. Findings have
      the potential to inform investigations and interventions in the context of
      treatment of HIV disease and other medical conditions.

PMID- 17436075
TI  - Nonsupportive peer norms and incarceration as HIV risk correlates for young black
      men who have sex with men.
AB  - Black men who have sex with men (BMSM) are at considerable risk for HIV
      infection. A convenience sample of BMSM (n=252) attending nightclubs in three
      North Carolina cities was surveyed to investigate factors associated with
      unprotected anal intercourse (UAI). About 45% reported UAI in the past 2 months.
      BMSM who strongly agreed that their male friends used condoms for anal sex were
      significantly less likely to report any UAI. Recently incarcerated men were
      significantly more likely to report unprotected insertive anal sex. In secondary
      analyses, men who reported experiencing discrimination based on their race and
      nongay identified men reported more favorable peer norms for condom use. Men who
      reported that their family disapproved of their being gay were more likely to
      have been incarcerated in the past 2 months. HIV prevention for BMSM must promote
      supportive peer norms for condom use and address incarceration, racial
      discrimination, and family disapproval.

PMID- 17436076
TI  - The Treatment Advocacy Program--Sinai: a peer-based HIV prevention intervention
      for working with African American HIV-infected persons.
AB  - As HIV/AIDS continues to disproportionately affect African American communities,
      there is a growing need for empirically based, culturally appropriate, tailored
      interventions for this clientele. As part of a Health Resources and Services
      Administration (HRSA)/Special Projects of National Significance (SPNS) initiative
      to increase prevention amongst those living with HIV, we implemented the
      Treatment Advocacy Program Intervention at Mount Sinai Hospital in Chicago, IL,
      USA. The main goal of the intervention was to help patients increase their
      medication adherence and sexual safety skills. This paper describes the rationale
      for implementing this peer-based HIV-prevention intervention, discusses how the
      intervention was tailored to work within our low socio-economic status, urban
      patient population, and reviews the training and quality assurance activities
      needed to integrate the intervention into our primary care clinic. We review the
      intervention content in detail, including the structure of the multiple, one-on
      one education sessions, and the core topics covered (medication adherence and
      sexual safety). Finally, we discuss the challenges in implementing this program,
      many of which arise from the chaotic social situations that our patients
      experience.

PMID- 17436077
TI  - Pediatrician perspectives on children's access to mental health services:
      consequences and potential solutions.
AB  - This paper examines pediatricians' perspectives regarding access to children's
      mental health care. In response to a question about factors that help or hinder
      coordination of care 190 respondents voluminously wrote about mental health
      access barriers. Responses were qualitatively analyzed to understand
      pediatricians' perspectives. Four thematic areas emerged: Insurance issues;
      availability of mental health specialty providers; state mental health systems;
      and pediatricians' attempts to improve access to mental health services.
      Pediatricians' responses included educating themselves, using telemedicine, and
      hiring co-located mental health specialists. Recommendations are made to address
      pediatricians' treatment of children with mental illnesses and their access to
      treatment resources.

PMID- 17436078
TI  - Quality of seeds produced by Psychotria tenuinervis (Rubiaceae): distance from
      anthropogenic and natural edges of Atlantic forest fragment.
AB  - The aim of this study was to investigate whether there were differences in the
      genetic variability and rate and velocity of the seed germination produced by
      Psychotria tenuinervis located at anthropogenic edges, natural edges, and in the
      forest interior. The populations of P. tenuinervis showed no differences in
      genetic variability or structure among the three habitats. There was, however, an
      indication of inbreeding, which was significantly higher in natural edges than in
      anthropogenic edges and the forest interior. Within-habitat variation was
      considerable, but there were no differences in seed mass or rate and velocity of
      germination among the three habitats. These results suggest that seed
      characteristics were not influenced by the genetic pattern of P. tenuinervis and
      that other characteristics of the forest fragment, such as gaps, edge age, and
      type of matrix exert more influence on seed mass and germination than the
      distance from the edges.

PMID- 17436079
TI  - Building capability throughout a change effort: leading the transformation of a
      police agency to community policing.
AB  - This case describes a change effort to move a police agency to become a community
      policing organization. The community policing effort was seen as a means to make
      a transformational change to become a learning organization with the goal of
      improving the delivery of police services. The case describes the steps taken to
      meet the new vision of community policing as well as the steps taken to deal with
      the challenges or realities of trying to make change happen. The lens for this
      case is the leadership role across the stages of change (exploration, planning,
      implementation, monitoring and institutionalization) in building capacity within
      the organization to sustain the change effort. The capacity building focused on
      incorporating systems thinking into the mindset of the members of the
      organization, breaking down the command and control mindset by building a new
      norm around high involvement of committed teams, and developing skill sets to
      support continuous learning and improvement in order to align organizational
      systems. A key lesson learned is that effective leaders do not just prepare an
      organization prior to a change effort. They must have the patience to constantly
      build the capacity for change among organizational members throughout the various
      stages of the change effort.

PMID- 17436080
TI  - A systems framework for understanding social settings.
AB  - In this paper, we argue that attempts to change social settings have been
      hindered by lack of theoretical advances in understanding key aspects of social
      settings and how they work in a dynamic system. We present a systems framework
      for understanding youths' social settings. We focus on three aspects of settings
      that represent intervention targets: social processes (i.e., patterns of
      transactions between two or more people or groups of people), resources (i.e.,
      human, economic, physical, temporal resources), and organization of resources
      (i.e., how resources are arranged and allocated). We postulate that these setting
      aspects are in dynamic transaction with each other, resulting in setting
      outcomes. Discussion focuses on the implications of our theoretical framework for
      setting intervention.

PMID- 17436081
TI  - Alpha1,3 Fucosyltransferase-VII modifies the susceptibility of apoptosis induced
      by ultraviolet and retinoic acid in human hepatocarcinoma cells.
AB  - The role of alpha1,3fucosyltransferase-VII (alpha1,3 FucT-VII) in cell apoptosis
      was studied in human hepatocellular carcinoma H7,721 cells. After the cells were
      transfected with alpha1,3 FucT-VII cDNA, the expression of apoptotic protease,
      procaspase-3, was decreased, while the anti-apoptotic proteins, phospho-PKB and
      phospho-Bad were increased as compared with mock (vector) transfected cells,
      indicating that alpha1,3FucT-VII is a potential anti-apoptotic factor in H7,721
      cells. After "alpha1,3FucT-VII" cells were irradiated by UV to induce apoptosis,
      the anti-apoptotic potential of alpha1,3FucT-VII became more apparent, as
      evidenced by the less apoptotic cell % and active cleaved caspase-3, more phospho
      p38 MAPK and JNK (two anti-apoptotic signaling molecules in H7,721 cells
      responsible to UV stress) when compared with the "Mock" cells. In contrast,
      "alpha1,3FucT-VII" cells facilitated the apoptosis induced by all-trans retinoic
      acid (ATRA), which was verified by the greater sub-G1 (apoptotic cells) peak in
      flow cytometry analysis, more expressions of active caspase-3 and pro-apoptotic
      protein Bax, as well as less expressions of anti-apoptotic proteins, Bcl-2 and
      Bcl-X(L). The up regulation of alpha1,3FucT-VII mRNA and cell surface SLe(x)
      (alpha1,3FucT-VII product) by UV and down regulation of them by ATRA was
      speculated to be one of the mechanisms that alpha1,3FucT-VII decreased and
      increased the susceptibility of apoptosis induced by UV and ATRA respectively.

PMID- 17436082
TI  - Prokinetic effects of a new ghrelin receptor agonist TZP-101 in a rat model of
      postoperative ileus.
AB  - Postoperative ileus (POI) is a major cause of postoperative complications and
      prolonged hospitalization. Ghrelin, which is the endogenous ligand for the growth
      hormone secretagogue receptor, has been found to stimulate gastric motility and
      accelerate gastric emptying. The present study investigates whether TZP-101 (0.03
      1 mg/kg i.v.), a synthetic ghrelin-receptor agonist, could improve
      gastrointestinal transit in rats with POI. Since the main factors for the
      development of POI are the surgical manipulation and the gastrointestinal effects
      of opioid-receptor agonists used for pain management, the effect of TZP-101 was
      investigated in rats subjected to surgery, to morphine treatment (3 mg/kg s.c.),
      or to a combination of both. The results showed that TZP-101 is equally effective
      against the delayed gastrointestinal transit induced by surgery, by morphine, or
      by the combination of both interventions. The prokinetic action of TZP-101 was
      more pronounced in the stomach compared to the small intestine.

PMID- 17436083
TI  - Noncardiac chest pain--an Asia-Pacific survey on the views of primary care
      physicians.
AB  - Noncardiac chest pain (NCCP) is common and has a significant impact on health
      care. Primary care physicians (PCPs)' attitudes, clinical approach, preference of
      diagnostic tests, referral patterns, and comfort in managing patients with NCCP
      in the Asia-Pacific region are not known. Consequently, we performed this survey
      in the Asia-Pacific region. The self-completed questionnaire was sent to PCPs in
      the Asia-Pacific region. A 28-item questionnaire contained questions on
      demographic information, characteristics of practice, preferences of diagnostic
      tests, referral patterns, treatment plans, and opinion on Helicobacter pylori and
      NCCP. A total of 108 (74%) PCPs returned the questionnaire. A mean of 18% of the
      patients were diagnosed with NCCP by PCPs in the past 6 months. Ninety-four
      percent of PCPs had treated NCCP patients in the last 6 months. Only 38% of the
      PCPs were comfortable in diagnosing NCCP but 85.2% believed that they should
      manage NCCP patients. PCPs in Malaysia and Philippines were more likely to refer
      patients to subspecialists. Fifty-seven and four-tenths percent of PCPs believed
      that H. pylori infection plays a role in the development of NCCP. The study
      demonstrates clearly that the understanding, diagnostic strategies, and treatment
      strategies of NCCP in the Asia-Pacific region are suboptimal and thus highlights
      the importance of educational and training programs tailored for PCPs in NCCP.

PMID- 17436084
TI  - Biermer's anemia: a new cause of cholestasis and hepatic steatosis?

PMID- 17436085
TI  - Rosiglitazone attenuates liver inflammation in a rat model of nonalcoholic
      steatohepatitis.
AB  - Rosiglitazone is an insulin-sensitizing agent. We aimed to assess the effects of
      rosiglitazone on a methionine- and choline-deficient diet (MCDD) model of
      nonalcoholic steatohepatitis (NASH) in rats. Wistar rats were fed either MCDD or
      a control diet in the 4-week induction study; they were given saline or 4
      mg/kg/day rosiglitazone. After the induction study period, the rats were divided
      into four groups and fed MCDD or given a control diet for an additional 8 weeks
      and received saline or rosiglitazone. Serum and tissue samples were obtained.
      Rosiglitazone improved inflammation in NASH and improved ALT, alkaline
      phosphatase, and interleukin-6 levels in the induction study and interleukin
      1beta, interleukin-6, and tumor necrosis factor-alpha levels in the treatment
      study. Our preliminary study is the first to show the anti-inflammatory effects
      of rosiglitazone in NASH. Rosiglitazone's effect on cytokines may be a key
      mechanism of its anti-inflammatory effect in NASH.

PMID- 17436086
TI  - The effect of acetaldehyde on human plasma factor XIII function.
AB  - The effect of acetaldehyde on the transglutaminase activity in pooled normal
      human plasma has been investigated. In this study, 0.05, 0.2, and 0.7 ml of
      pooled human plasma were preincubated for 30 min. at room temperature with buffer
      or acetaldehyde at final concentrations of 40.6, 22.4, and 11.2 mM before being
      utilized for Factor XIIIa assay with fibrinogen and thrombin which had been
      preheated at 40 degrees C to destroy endogenous Factor XIII/XIIIa activity. At
      all concentrations of acetaldehyde and all concentrations of plasma-containing
      Factor XIII which were employed, prolongation of both clotting time and
      stabilization time was observed. The 11.2 mM acetaldehyde is within the range of
      daily acetaldehyde production to be predicted in severe alcoholics as a
      consequence of imbibing alcohol. The stabilization times measured for Factor
      XIIIa activity appear to be the most sensitive to acetaldehyde compared to
      acetaldehyde effects on thrombin, Factor Xa, and fibrinogen studied earlier in
      this laboratory, as well as Factors II, VII, and X.

PMID- 17436087
TI  - Causes of death in patients with unresectable hepatocellular carcinoma.
AB  - Most patients with hepatocellular carcinoma (HCC) also have cirrhosis, an
      independent cause of death. We considered an alternative definition of tumor
      related death in patients with HCC and attempted to validate our definition. Two
      hundred thirty-seven HCC patients were diagnosed, followed, and died over a 12
      year period and were evaluated every 2 months, including their last 6 months of
      life. We defined death by cancer if there was, in the last 6 months of life, a CT
      scan increase of >25% in the sum of tumor index lesions' cross-sectional areas or
      new onset of, or increase in, either vascular invasion or metastatic disease
      (Group 1). Patients with stable cancer were considered to have died from any
      other cause (Group 2). We found that 135 (57%) patients died from cancer
      progression (Group 1), whereas 102 (43%) patients did not (Group 2). There was a
      statistically significant difference between Group 1 and Group 2 patients in
      percentage with bilobar disease (P = 0.03), more than one tumor (P = 0.01), an
      increase in AFP (P = 0.04), vascular invasion (P = 0.001), and the presence of
      metastases (P = 0.01). We conclude that 57% of patients with unresectable HCC
      died as a direct result of cancer progression, but 43% did not. The latter died
      from complications of their cirrhosis, including sepsis, GI bleeds, and renal
      failure.

PMID- 17436088
TI  - Effects of nanocrystalline silver (NPI 32101) in a rat model of ulcerative
      colitis.
AB  - Nanocrystalline silver (NPI 32101) has been demonstrated to have antimicrobial
      and anti-inflammatory properties. The purpose of this study was to assess the
      effect of NPI 32101 in a rat model of ulcerative colitis and the possible
      mechanisms of action of the effects observed. NPI 32101, 4 mg/kg intracolonically
      or 40 mg/kg orally, significantly reduced colonic inflammation compared to the
      placebo and no-treatment groups. Sulfasalazine (100 mg/kg), either
      intracolonically or orally, also reduced colonic inflammation. NPI 32101
      significantly suppressed the expression of matrix metalloproteinase (MMP)-9,
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-12, whereas
      sulfasalazine suppressed MMP-9, IL-1beta, and TNF-alpha, but not IL-12, compared
      to placebo. MMP-9 activity was reduced by NPI 32101 and sulfasalazine. NPI 32101
      administered intracolonically or orally decreases ulcerative colitis in a rat
      model and is as effective as sulfasalazine. NPI 32101 treatment suppresses the
      expression and activity of MMP-9 and the expression of TNF-alpha, IL-1beta, and
      IL-12, mechanisms by which NPI 32101 may exert its anti-inflammatory effects. NPI
      32101 may have therapeutic potential for treatment of ulcerative colitis.

PMID- 17436089
TI  - Chylous ascites secondary to pancreatitis: management of an uncommon entity using
      parenteral nutrition and octreotide.
AB  - Malignancy, surgical trauma, cirrhosis and tuberculosis account for more than 95%
      of causes for chylous ascites. We report a case of persistent chylous ascites
      following acute pancreatitis that responded to parenteral nutrition and
      octreotide. A 50 year-old male was diagnosed with acute alcoholic pancreatitis
      after presenting with typical abdominal pain, and elevated amylase and lipase.
      The acute symptoms resolved within one week. Four weeks later he started
      developing increased abdominal girth. Examination revealed the presence of
      shifting dullness and paracentesis confirmed diagnosis of chylous ascites.
      Investigations for the common causes of chylous ascites were negative.
      Laparoscopy confirmed the presence of fat necrosis within mesenteric lymph nodes
      linking the chylous ascites to the episode of pancreatitis. The Chylous ascites
      was resistant to the usual medical therapy, but responded only to the combination
      of octreotide and total parenteral nutrition with complete resolution of ascites
      in 8 weeks. This case of chylous ascites secondary to pancreatitis represents an
      uncommon presentation with effective management resulting in a dramatic response.

PMID- 17436090
TI  - Reproducibility of 24-hour combined multiple intraluminal impedance (MII) and pH
      measurements in infants and children. Evaluation of a diagnostic procedure for
      gastroesophageal reflux disease.
AB  - Gastroesophageal reflux disease (GERD) is a common disease in infants and
      children. Prolonged (24-hr) pH monitoring in the esophagus for determination of
      increased acid exposure has, together with endoscopy, been the only routinely
      implemented method for GERD diagnosis. The recently introduced multiple
      intraluminal impedance (MII) provides additional information about the number of
      both acid and nonacid episodes of retrograde bolus movement in the esophagus. The
      aim of this study was to investigate the day-to-day reproducibility and the
      interobserver variability of 24-hr combined MII (number of nonacid and acidic
      reflux episodes) and pH in the esophagus in infants and children. Upper endoscopy
      followed by 2 x 24-hr consecutive combined MII and pH monitoring was performed in
      33 infants and children referred to a tertiary center for evaluation of GERD. The
      study was performed in a hospital setting without dietary restrictions. Bland
      Altman difference versus mean plots and calculation of the limits of agreement
      (LOA) were used for assessment of the reproducibility of the total number of
      acidic and nonacidic reflux episodes. LOA for the number of acidic reflux
      episodes on day 2 were 0.2-5.3 times the value obtained on day 1. For the total
      number of nonacidic reflux episodes, LOA were 0.04-8.6; for the total number of
      reflux episodes, 0.3-3.3. An abnormal reflux index on one or both recording days
      was found in 7 of 30 patients. In conclusion, considerable day-to-day variability
      was found for nonacidic reflux episodes. Less variability was found for acidic
      reflux episodes. This variability must be taken into consideration for the use of
      MII in the clinical evaluation of infants and children with GERD.

PMID- 17436091
TI  - Fulminant hepatic failure in an African setting: etiology, clinical course, and
      predictors of mortality.
AB  - This is prospective cross-sectional study on 37 patients presenting to different
      hospitals in Khartoum state, Sudan, sought to determine the etiology, clinical
      course, and predictors of mortality in patients presenting with fulminant hepatic
      failure (FHF). Patients were subclassified into hyperacute, acute, and subacute
      FHF; all sera were tested for hepatitis A, B, C, and E; negative samples were
      tested for antinuclear antibodies and anti-smooth muscle antibodies. The
      commonest etiologic factors included seronegative hepatitis (38%), hepatitis B
      virus (22%), severe Plasmodium falciparum malaria (8%), autoimmune hepatitis
      (8%), hepatitis E virus (5%), anti-tuberculous drugs (5%), and lymphomatous
      infiltration of the liver (5%). The mortality rate was high at 84%. Poor
      prognostic factors included presentation with grade III/IV encephalopathy,
      evidence of bacterial infection, and a prolonged prothrombin time of >25 seconds
      over the controls.

PMID- 17436092
TI  - Preventing relapse of major depression during interferon-alpha therapy for
      hepatitis C--A pilot study.
AB  - Depression is common in hepatitis C, exacerbated by interferon, and is a major
      reason for discontinuing interferon therapy. We aimed to determine (1) whether
      patients with a history of major depression could complete a course of
      peginterferon alpha-2a and ribavirin if pretreated with escitalopram and (2) the
      relapse rate of depression during the course of therapy in these subjects. Ten
      patients were enrolled in the study and treated with escitalopram. The Hamilton
      Depression Rating Scale (Ham-D) and other psychiatric scales were administered
      throughout the study. There were no statistically significant increases in mean
      Ham-D scores. No subjects were discontinued from the study due to depression
      relapse. Nine of 10 subjects maintained remission of depression throughout the
      study. We conclude that pretreatment with escitalopram in subjects with major
      depressive disorder in remission may prevent recurrence of major depression
      during a course of interferon and ribavirin therapy for hepatitis C.

PMID- 17436093
TI  - Endoscopic biliary stent migration to the iliopsoas muscle in a liver transplant
      recipient: percutaneous removal.

PMID- 17436094
TI  - The practice of percutaneous liver biopsy in a gastrohepatology day hospital: a
      retrospective study on 835 biopsies.
AB  - The evolving role of liver biopsy has induced the formulation of several
      guidelines on its appropriateness. However, the great divergence among
      hepatologists is still unresolved. We report the 4-year activity of a day
      hospital of gastrohepatology in northern Italy. Between January 2001 and July
      2004, 835 subjects (mean age, 43+/-12 years) underwent this procedure in our
      facility. Etiologically, in 465 (56%) and 157 (19%) patients, chronic hepatitis C
      and nonspecific elevated liver biochemical tests were the first and second
      indications, followed by chronic hepatitis B and suspected nonalcoholic
      steatohepatitis. On a purpose basis, procedures requested for staging (n = 578)
      and/or for diagnosis (n = 217) were identified. Among the former, 80% had the
      scope of staging chronic hepatitis C, and in 15% of these unsuspected
      superimposed cirrhosis was detected. Among diagnostic procedures, nonspecific
      raised liver enzyme level ranked first. Twenty-two percent of patients reported
      unwanted effects following the procedure. In conclusion, these data accord with
      indications expressed by international guidelines. The impact of liver biopsy on
      therapeutic decision-making needs to be studied further.

PMID- 17436095
TI  - Effects of pentoxifylline on TNF-alpha production by peripheral blood mononuclear
      cells in patients with nonalcoholic steatohepatitis.
AB  - Pentoxifylline (POF) is a new candidate for the treatment of nonalcoholic
      steatohepatitis (NASH). Its effects on the cytokine production in patients with
      NASH are not completely understood. This study was designed to investigate the
      effect of POF on TNF-alpha production by peripheral blood mononuclear cells
      (PBMC) in patients with NASH. After preliminary experiments in healthy control
      subjects to determine the range of POF concentration to be used in NASH patients,
      PBMCs from patients with NASH (n = 13) were cultured in the presence of
      lipopolysaccharide (LPS, 100 ng/ml) and various concentrations of POF for 24 hr.
      Concentrations of TNF-alpha in culture supernatants were measured by ELISA and
      the transcriptional activity was determined by RT-PCR. As dictated by the results
      of our preliminary study in PBMC from healthy control subjects, we treated LPS
      stimulated PBMCs from NASH patients with 10, 100, and 500 microg/ml of POF.
      Stimulation of PBMCs from NASH patients with LPS resulted in a strong up
      regulation of TNF-alpha production from median 355.9 (interquartile range, 206.7
      463.5) pg/ml to 1,670 pg/ml (interquartile range, 1,121-2,414) pg/ml. In this LPS
      stimulated culture system, POF caused a dose-dependent suppression of TNF-alpha
      levels (P < 0.001, ANOVA on ranks for repeated measures). TNF-alpha levels in
      culture supernatants decreased to 870.3 (range, 598.3-2,077) pg/ml with 10
      microg/ml of POF treatment, and to levels similar to those obtained in baseline
      unstimulated cultures (133.4 (range, 95.8-1518.5) pg/ml) at 100 microg/ml. At 500
      microg/ml, POF suppressed TNF-alpha production to levels significantly lower than
      that obtained in unstimulated (baseline) culture supernatants (76.3 (range, 33
      94.5) pg/ml; P = 0.001). The mRNA expression was consistent with the effects on
      protein concentration. Demographic characteristics of the patients, laboratory
      results, such as AST, ALT, alkaline phosphatase, GGT, and triglyceride levels,
      and the liver histology did not seem to influence the in vitro TNF-alpha response
      of the PBMCs from NASH patients. POF can significantly decrease the LPS
      stimulated TNF-alpha production by PBMCs in NASH patients. Our results support
      the notion that POF might be a good candidate for the treatment of NASH.

PMID- 17436096
TI  - Apolipoprotein-AII concentrations are associated with liver steatosis in patients
      with chronic hepatitis C.
AB  - It has been shown that the hepatitis C virus (HCV) core protein reduces the
      activity of the microsomal triglyceride transfer protein (MTP) and could lead to
      steatosis in HCV-infected patients. Experimentally, apolipoprotein-AII (apoAII),
      which restores triglyceride secretion altered by the HCV core protein, could be
      protective against HCV steatosis. On the other hand, increasing plasma
      concentrations of mouse apoAII in transgenic mice produced several aspects of
      insulin-resistance syndrome, which also is implicated in the pathogenesis of HCV
      steatosis. This study was designed to investigate the role of apoAII in HCV
      related steatosis in humans. Sixty-five hospitalized patients with chronic HCV
      were included in this study to assess the effects of apoAII, body mass index
      (BMI), age, insulin sensibility (HOMA), and leptin level on steatosis. Steatosis
      was observed in 55.3% of patients. Apo-AII was significantly associated with HOMA
      and with leptin concentrations. In univariate analyses, age, BMI, increased
      leptin level, increased HOMA, and increased apoAII concentration were associated
      with steatosis. In multivariate analysis, steatosis was associated with apoAII
      concentration, age, gender, and BMI. Contrary to previous hypotheses, apoAII is
      not a protective factor against HCV steatosis but is significantly associated
      with the development of liver steatosis. The fact that the plasma levels of
      apoAII correlate with HOMA and leptin levels in HCV-infected patients suggests
      that apoAII may contribute to hepatic steatosis progression in relationship to
      visceral obesity, insulin resistance, and metabolism of triglyceride-rich
      lipoproteins.

PMID- 17436097
TI  - The effects of N-acetylcysteine on bile duct ligation-induced liver fibrosis in
      rats.
AB  - Stellate cells are activated by free radicals, and synthesize collagen. N
      acetylcysteine (NAC) is a precursor of reduced glutathione and a potent scavenger
      of hydroxyl radicals and has potential antifibrotic effects. We aimed to test the
      effects of NAC on bile duct ligation (BDL) induced liver damage in rats. Forty
      seven Wistar rats were divided into 5 groups: group 1, BDL+NAC (n=10); group 2,
      BDL (n=10); group 3, sham+NAC (n=10); group 4, sham (n=10); and group 5, control
      group (n=10). NAC (50 micromol/kg per day) or saline of single doses were
      administered intraperitoneally for 28 days. Serum biochemical and liver oxidative
      stress parameters were studied. Liver collagen level was determined by the method
      of Lopez de Leon and Rojkind. Liver slides were stained by hematoxylin and eosin
      and Masson trichrome?Gomory reticulum staining. Aspartate aminotransferase (AST)
      and alkaline phosphatase levels in the BDL+NAC group were lower than the BDL
      group and were higher than the control groups (all P< .001). Malondialdehyde,
      luminal, and glutathione levels in group 1 were lower than the BDL group (P= .01,
      P= .002, and P< .001) and higher than the control groups (all P< .001). NAC had
      no effect on alanine aminotransferase (ALT), gammaglutamyl transferase,
      bilirubin, albumin, or lucigenin levels. Liver collagen levels were higher in the
      BDL groups (P< .001); however, NAC had no effect on the collagen levels. The BDL
      groups showed stage 3 fibrosis; all the control groups were normal. NAC improved
      some biochemical parameters (AST, alkaline phosphatase) and oxidative stress
      parameters (malondialdehyde, luminol, glutathione) in the BDL model. NAC was
      found to be effective on cholestasis-induced hepatotoxicity. However, NAC was
      inefficient as an antifibrotic agent within a 1-month period of administration in
      the BDL model.

PMID- 17436098
TI  - Rodent IRR-219 (IgGFcgammaBP) and rTFF3, expressed mainly in the intestinal
      mucosa, depleted during dextran sulfate sodium-induced colitis.
AB  - IgGFcgammaBP and TFF3 are related with adaptation during injury, mucosal defense,
      and epithelial healing. In this work, we produced the polyclonal antibodies for
      rat IgGFcgammaBP or TFF3 and assessed their tissue distributions in adult and
      prenatal rats, rTFF3 molecular patterns under reduced and nonreduced condition,
      involvement of IgGFcgammaBP, and TFF3 in dextran sulfate sodium (DSS)-induced
      colitis. Polyclonal antibodies of rat IgGFcgammaBP or TFF3 were produced with
      their synthetic polypeptide. Rat TFF3 was detected in the scraped intestinal
      mucosa by SDS/PAGE and Western blotting. Immunohistochemical stainings of rat
      IgGFcgammaBP or TFF3 were performed in different tissues, mainly in mucin
      producing tissues, of adult rat and prenatal rat intestine. Rat IgGFcgammaBP and
      TFF3 were immunohistochemically detected in the distal colon of rat colitis model
      induced with 7% DSS. IgGFcgammaBP and TFF3 were mainly expressed in the
      intestinal mucosa with different distribution patterns. The scattered staining
      was also found in the epithelium of bile duct. There was strong expression of
      IgGFcgammaBP and TFF3 in rat embryonic intestine. There were two kinds of rTFF3
      complexes existed with different molecular weights, 250 and 55 kDa, under
      nonreduced conditions, but shifted to 6 kDa under reduced conditions. In the DSS
      induced colitis model, IgGFcgammaBP and TFF3 were significantly decreased in the
      distal colon mucosa at the onset and active phases comparing with the normal
      control, partially recovered at the regenerative phase. Based on these
      findings,IgGFcgammaBP and TFF3 were widely expressed in the intestinal mucosa,
      depleted during DSS-induced colitis. Rat TFF3 existed mainly in two complexes
      with 250 and 55 kDa molecular weights. The present findings indicate they are two
      important goblet cell-derived components possibly related to the pathogenesis of
      DSS-induced colitis, a rat model of ulcerative colitis.

PMID- 17436099
TI  - X-linked hyper-IgM syndrome associated with poorly differentiated neuroendocrine
      tumor presenting as obstructive jaundice secondary to extensive adenopathy.
AB  - X-Linked Hyper IgM Syndrome (XHIGM) is a rare B-cell immunodeficiency disease.
      Patients with XHIGM are unable to switch immunoglobulin production from IgM to
      IgG, IgA, and IgE. Patients with XHIGM require periodic intravenous immune
      globulin to help prevent infections, and are also at risk for a variety of
      neoplasms. We describe a young man with XHIGM who presented with obstructive
      jaundice from malignant adenopathy from widespread, poorly differentiated
      neuroendocrine tumor. This has not previously been reported and represents a new
      association with XHIGM.

PMID- 17436100
TI  - Paraoxonase (PON)1 192R allele carriage is associated with reduced risk of
      inflammatory bowel disease.
AB  - The paraoxonase (PON) genes family maps to chromosome 7q21-q22, within a loci
      that also showed evidence of susceptibility genes for both Crohn's disease (CD)
      and ulcerative colitis (UC). In this case-control study we investigated the
      possible relationship between PON1 and PON2 polymorphisms and the risk of
      inflammatory bowel disease (IBD). PON1 192Q/R, PON1 55L/M, and PON2 311S/C
      polymorphisms were investigated by RFLP analysis in DNA samples from 224 patients
      with CD, 58 patients with UC, and 311 healthy controls. The PON1 192R allele was
      significantly less common among IBD Ashkenazi patients (allelic OR = 0.61, P =
      0.004, 95% CI = 0.44-0.85). In agreement with the individual SNP analysis,
      Ashkenazi IBD patients had a higher frequency of haplotype PON1 192Q/PON1
      55L/PON2 311S (26.3% vs 17.3%; P=0.003) and a lower frequency of haplotype PON1
      192R/PON1 55L/PON2 311S (18.9% vs 27.7%; P=0.008). Our results suggest that in
      this Ashkenazi Jewish population, carriage of PON1 R192 allele may confer
      protection against the development of IBD.

PMID- 17436101
TI  - Influence of radiofrequency energy delivery at the gastroesophageal junction (the
      Stretta procedure) on symptoms, acid exposure, and esophageal sensitivity to acid
      perfusion in gastroesophagal reflux disease.
AB  - Several studies have demonstrated that radiofrequency energy delivery at the
      gastroesophageal junction (the Stretta procedure) induces symptom relief in
      gastroesophageal reflux disease (GERD), although improvement of acid exposure on
      pH monitoring was usually limited. A role for decreased esophageal sensitivity
      has been suggested. Our aim was to evaluate the influence of Stretta on symptoms,
      acid exposure, and sensitivity to esophageal acid perfusion in GERD. Thirteen
      patients with established proton pump inhibitor (PPI)-dependent GERD (three
      males; mean age, 51+/-10 years) participated in the study. Before and 6 months
      after the procedure symptom score, pH monitoring and Bernstein acid perfusion
      test were performed. The latter was done by infusing HCl (pH 0.1) at a rate of 6
      ml/min 15 cm proximal to the gastroesophageal junction for a maximum of 30 min or
      until the patients experienced heartburn. Results were compared by Student's t
      test. Stretta procedure time was 51+/-4 min and no complications occurred. After
      6 months, the symptom score was significantly improved (12.5+/-2.0 to 7.5+/-2.1;
      P<0.05), seven patients no longer needed daily PPI, and acid exposure was
      significantly decreased (11.6%+/-1.6% to 8.5%+/-1.8% of time pH<4; P<0.05). The
      time needed to induce heartburn during acid perfusion decreased from 9.5+/-2.3 to
      18.1+/-3.4 min (P=0.01), and five patients became insensitive to 30-min acid
      perfusion, versus none at baseline (P=0.04). In conclusion, the Stretta procedure
      induces subjective improvement of GERD symptoms and decreases esophageal acid
      exposure. In addition, esophageal acid sensitivity is decreased 6 months after
      the Stretta procedure. The mechanism underlying this finding and its relevance to
      symptom control require further studies.

PMID- 17436102
TI  - CRP correlates with clinical score in ulcerative colitis but not in Crohn's
      disease.
AB  - The aim of this study was to prospectively evaluate the correlation between
      clinical scoring systems and C-reactive protein (CRP) in inflammatory bowel
      disease. The modified Harvey-Bradshaw index was used in 40 patients (58
      assessments) with Crohn's disease, and the Lichtiger score in 29 patients (36
      assessments) with ulcerative colitis. In ulcerative colitis, CRP was elevated in
      14%, 42%, 64%, and 83%, respectively, of subjects with quiescent, mild, moderate,
      and severe disease. There was a linear correlation of log(CRP) with clinical
      score except for proctitis. In Crohn's disease, CRP was elevated in 54%, 70%,
      75%, and 100%, respectively, of subjects with quiescent, mild, moderate, and
      severe disease. We conclude that the clinical score has a good correlation with
      CRP in ulcerative colitis except for proctitis, whereas clinical score has a poor
      correlation with CRP in Crohn's disease, particularly in those with clinically
      quiescent, fibrostenotic, and ileal disease.

PMID- 17436103
TI  - Effect of proton pump inhibitor therapy on inflammatory changes in the gastric
      cardia (carditis).
AB  - The etiology of inflammation of the gastric cardia (carditis) is controversial,
      and gastroesophageal reflux disease (GERD) and H. pylori infection have been
      proposed as etiological factors. This study aimed to investigate the effect of
      acid suppression on histological changes in the gastric cardia. Gastric cardia
      biopsies of reflux patients were evaluated at baseline and after proton pump
      inhibitor (PPI) therapy. The updated Sydney classification was used to score the
      biopsies, and carditis scores (pre- and post-PPI therapy) were compared. A total
      of 31 patients were included, of which 5 patients were excluded, as cardiac
      mucosa was not documented in either pre- or post-PPI biopsies. The mean duration
      of PPI therapy was 30 months (SE, 3.04 months). There was no significant change
      in carditis scores post-PPI therapy. The mean mononuclear and neutrophil scores
      were 1.23 and 0.35 pre-PPI therapy and 1.73 and 0.62 post-PPI therapy,
      respectively. No change in mean intestinal metaplasia and atrophy scores was
      identified. In conclusion, acid suppressive therapy with PPI did not lead to a
      significant reduction in carditis scores. These results suggest that GERD
      probably does not play a major role in the pathogenesis of inflammation in the
      gastric cardia.

PMID- 17436104
TI  - Correlation between gastrointestinal symptoms and gastric leptin and ghrelin
      expression in patients with gastritis.
AB  - The purpose of this study was to examine the changes in gastric ghrelin and
      leptin with respect to Helicobacter pylori infection and whether such changes
      affect the plasma levels of leptin and ghrelin. In addition, we examined the
      relationship between changes in gastric mucosal ghrelin and leptin levels and
      gastrointestinal symptoms. Sixty-three patients diagnosed with chronic gastritis
      were enrolled in the study. Twenty-nine patients were Helicobacter pylori
      negative and 34 were Helicobacter pylori positive. Expression of ghrelin and
      leptin mRNA in the gastric mucosa was measured using endoscopic biopsies from the
      fundus. Plasma levels of ghrelin and leptin were measured by radioimmunoassay.
      Expression of leptin mRNA in the gastric mucosa was significantly higher in
      Helicobacter pylori-positive patients than in negative patients (0.38 +/- 0.17
      vs. 0.24 +/- 0.12, p = 0.039). The expression of ghrelin was lower in positive
      patients than in the negative group, although this difference was not significant
      (p = 0.07). However, there was no significant difference in plasma leptin and
      ghrelin levels. Gastric mucosal ghrelin mRNA expression was significantly lower
      in patients with dyspepsia than in those without (0.15 +/- 0.11 vs. 0.23 +/-
      0.20, p = 0.05). Helicobacter pylori infection and gastrointestinal symptoms
      could be associated with leptin and ghrelin expression in the gastric mucosa.

PMID- 17436105
TI  - Development of specific antibodies to an ARF protein in treated patients with
      chronic HCV infection.
AB  - The hepatitis C virus (HCV) F protein is a recently described, frameshift product
      of HCV core encoding sequence with unknown biological function. In this study we
      sought to characterize the prevalence of specific anti-F antibodies in patients
      with chronic HCV infection and to analyze the anti-F antibody profile before,
      during, and after antiviral treatment in order to gain a better understanding of
      the role of F protein in HCV pathogenesis. Serum samples were collected from 44
      patients with chronic HCV infection and from 19 healthy controls. Consecutive
      samples from 27 patients taken before, during, and after treatment with antiviral
      therapy. The F and the core proteins were cloned from the HCV genome. The
      recombinant proteins were expressed in Escherichia coli and affinity purified. A
      sensitive and specific enzyme-linked immunosorbent assay was developed to assess
      the prevalence of anti-F antibodies. Eighty-nine percent of chronic HCV patients
      had evidence of anti-F antibodies, and 95% of them had anti-core antibodies. No
      correlation of anti-F antibodies was found with response to treatment, genotype,
      or seroconversion. We conclude that the F protein elicits specific antibodies in
      most individuals chronically infected with HCV with no correlation with response
      to treatment. Our results confirm the expression of F protein during natural HCV
      infection.

PMID- 17436106
TI  - Thrombotic thrombocytopenic purpura and bone marrow necrosis associated with
      disseminated gastric cancer.

PMID- 17436107
TI  - Psychiatrists as administrators: the perspective of a mental health department
      psychiatrist.
AB  - This paper is adapted from the American Association of Psychiatric Administrators
      Annual Membership Luncheon Speech given at the meeting of the American
      Psychiatric Association in Toronto, Canada on May 23, 2006. The author discusses
      three experiences from his work for the New York City Department of Health and
      Mental Hygiene to illustrate how psychiatrists working as administrators are
      uniquely able to meet community mental health and substance misuse needs. The
      author describes public health interventions employed by psychiatric
      administrators to reduce morbidity and mortality from opioid and methamphetamine
      misuse.

PMID- 17436109
TI  - Mechanistic computational model of ovarian steroidogenesis to predict biochemical
      responses to endocrine active compounds.
AB  - Sex steroids, which have an important role in a wide range of physiological and
      pathological processes, are synthesized primarily in the gonads and adrenal
      glands through a series of enzyme-mediated reactions. The activity of
      steroidogenic enzymes can be altered by a variety of endocrine active compounds
      (EAC), some of which are therapeutics and others that are environmental
      contaminants. A steady-state computational model of the intraovarian metabolic
      network was developed to predict the synthesis and secretion of testosterone (T)
      and estradiol (E2), and their responses to EAC. Model predictions were compared
      to data from an in vitro steroidogenesis assay with ovary explants from a small
      fish model, the fathead minnow. Model parameters were estimated using an
      iterative optimization algorithm. Model-predicted concentrations of T and E2
      closely correspond to the time-course data from baseline (control) experiments,
      and dose-response data from experiments with the EAC, fadrozole (FAD). A
      sensitivity analysis of the model parameters identified specific transport and
      metabolic processes that most influence the concentrations of T and E2, which
      included uptake of cholesterol into the ovary, secretion of androstenedione (AD)
      from the ovary, and conversions of AD to T, and AD to estrone (E1). The
      sensitivity analysis also indicated the E1 pathway as the preferred pathway for
      E2 synthesis, as compared to the T pathway. Our study demonstrates the
      feasibility of using the steroidogenesis model to predict T and E2
      concentrations, in vitro, while reducing model complexity with a steady-state
      assumption. This capability could be useful for pharmaceutical development and
      environmental health assessments with EAC.

PMID- 17436108
TI  - Learning to translate sequence and structure to function: identifying DNA binding
      and membrane binding proteins.
AB  - A protein's function depends in a large part on interactions with other
      molecules. With an increasing number of protein structures becoming available
      every year, a corresponding structural annotation approach identifying such
      interactions grows more expedient. At the same time, machine learning has gained
      popularity in bioinformatics providing robust annotation of genes and proteins
      without sequence homology. Here we have developed a general machine learning
      protocol to identify proteins that bind DNA and membrane. In general, there is no
      theory or even rule of thumb to pick the best machine learning algorithm. Thus, a
      systematic comparison of several classification algorithms known to perform well
      is investigated. Indeed, the boosted tree classifier is found to give the best
      performance, achieving 93% and 88% accuracy to discriminate non-homologous
      proteins that bind membrane and DNA, respectively, significantly outperforming
      all previously published works. We also attempted to address the importance of
      the attributes in function prediction and the relationships between relevant
      attributes. A graphical model based on boosted trees is applied to study the
      important features in discriminating DNA-binding proteins. In summary, the
      current protocol identified physical features important in DNA and membrane
      binding, rather than annotating function through sequence similarity.

PMID- 17436110
TI  - Multi-scale computational models of pro-angiogenic treatments in peripheral
      arterial disease.
AB  - The induction of angiogenesis is a promising therapeutic strategy for the
      amelioration of peripheral arterial disease (PAD). This occlusive disease results
      in muscle ischemia, and neovascularization is a route to increasing the perfusion
      in the tissue. The vascular endothelial growth factor (VEGF) family of potent pro
      angiogenic cytokines is a potential therapeutic agent, increasing VEGF-receptor
      signaling on tissue vasculature. To investigate the effects of possible therapies
      on the VEGF concentrations and gradients within the tissue, we consider three
      such strategies: VEGF gene therapy (e.g. by adeno-associated virus); VEGF cell
      based therapy (injected myoblasts that overexpress VEGF); and chronic exercise
      (which upregulates VEGF receptor expression). The multi-scale computational model
      used to investigate these strategies is an integration of several components: an
      anatomical description of the muscle geometry and cell types; microvascular blood
      flow; tissue oxygen distribution; VEGF secretion from muscle fibers; VEGF
      transport through interstitial space; and VEGF-receptor binding on microvascular
      endothelial cells. Exercise training, which results in increased VEGF secretion
      in hypoxic tissue and increased VEGF receptor expression, exhibits increases in
      both VEGF concentration and VEGF gradients, and is predicted to be more effective
      than the other, VEGF-only treatments.

PMID- 17436111
TI  - MRI-guided thermal ablation therapy: model and parameter estimates to predict
      cell death from MR thermometry images.
AB  - Solid tumors and other pathologies can be treated using laser thermal ablation
      under interventional magnetic resonance imaging (iMRI) guidance. A model was
      developed to predict cell death from magnetic resonance (MR) thermometry
      measurements based on the temperature-time history, and validated using in vivo
      rabbit brain data. To align post-ablation T2-weighted spin-echo MR lesion images
      to gradient-echo MR images, from which temperature is derived, a registration
      method was used that aligned fiducials placed near the thermal lesion. The outer
      boundary of the hyperintense rim in the post-ablation MR lesion image was used as
      the boundary for cell death, as verified from histology. Model parameters were
      simultaneously estimated using an iterative optimization algorithm applied to
      every interesting voxel in 328 images from multiple experiments having various
      temperature histories. For a necrotic region of 766 voxels across all lesions,
      the model provided a voxel specificity and sensitivity of 98.1 and 78.5%,
      respectively. Mislabeled voxels were typically within one voxel from the
      segmented necrotic boundary with median distances of 0.77 and 0.22 mm for false
      positives (FP) and false negatives (FN), respectively. As compared to the
      critical temperature cell death model and the generalized Arrhenius model, our
      model typically predicted fewer FP and FN. This is good evidence that iMRI
      temperature maps can be used with our model to predict therapeutic regions in
      real-time during treatment.

PMID- 17436112
TI  - Multi-cell agent-based simulation of the microvasculature to study the dynamics
      of circulating inflammatory cell trafficking.
AB  - Leukocyte trafficking through the microcirculation and into tissues is central in
      angiogenesis, inflammation, and the immune response. Although the literature is
      rich with mechanistic detail describing molecular mediators of these processes,
      integration of signaling events and cell behaviors within a unified spatial and
      temporal framework at the multi-cell tissue-level is needed to achieve a fuller
      understanding. We have developed a novel computational framework that combines
      agent-based modeling (ABM) with a network flow analysis to study monocyte homing.
      A microvascular network architecture derived from mouse muscle was incorporated
      into the ABM. Each individual cell was represented by an individual agent in the
      simulation. The network flow model calculates hemodynamic parameters (blood flow
      rates, fluid shear stress, and hydrostatic pressures) throughout the simulated
      microvascular network. These are incorporated into the ABM to affect monocyte
      transit through the network and chemokine/cytokine concentrations. In turn,
      simulated monocytes respond to their local mechanical and biochemical
      environments and make behavioral decisions based on a rule set derived from
      independent literature. Simulated cell behaviors give rise to emergent leukocyte
      rolling, adhesion, and extravasation. Molecular knockout simulations were
      performed to validate the model, and predictions of monocyte adhesion, rolling,
      and extravasation show good agreement with the independently published
      corresponding mouse studies.

PMID- 17436114
TI  - Ethical dilemmas in community-based participatory research: recommendations for
      institutional review boards.
AB  - National and international codes of research conduct have been established in
      most industrialized nations to ensure greater adherence to ethical research
      practices. Despite these safeguards, however, traditional research approaches
      often continue to stigmatize marginalized and vulnerable communities. Community
      based participatory research (CBPR) has evolved as an effective new research
      paradigm that attempts to make research a more inclusive and democratic process
      by fostering the development of partnerships between communities and academics to
      address community-relevant research priorities. As such, it attempts to redress
      ethical concerns that have emerged out of more traditional paradigms.
      Nevertheless, new and emerging ethical dilemmas are commonly associated with CBPR
      and are rarely addressed in traditional ethical reviews. We conducted a content
      analysis of forms and guidelines commonly used by institutional review boards
      (IRBs) in the USA and research ethics boards (REBs) in Canada. Our intent was to
      see if the forms used by boards reflected common CBPR experience. We drew our
      sample from affiliated members of the US-based Association of Schools of Public
      Health and from Canadian universities that offered graduate public health
      training. This convenience sample (n = 30) was garnered from programs where
      application forms were available online for download between July and August,
      2004. Results show that ethical review forms and guidelines overwhelmingly
      operate within a biomedical framework that rarely takes into account common CBPR
      experience. They are primarily focused on the principle of assessing risk to
      individuals and not to communities and continue to perpetuate the notion that the
      domain of "knowledge production" is the sole right of academic researchers.
      Consequently, IRBs and REBs may be unintentionally placing communities at risk by
      continuing to use procedures inappropriate or unsuitable for CBPR. IRB/REB
      procedures require a new framework more suitable for CBPR, and we propose
      alternative questions and procedures that may be utilized when assessing the
      ethical appropriateness of CBPR.

PMID- 17436115
TI  - A tribute to Ariel Reyes.

PMID- 17436113
TI  - Role of functional magnetic resonance imaging in drug discovery.
AB  - In this review, we survey the state of the field of functional magnetic resonance
      imaging (fMRI) as it relates to drug discovery and drug development. We highlight
      the advantages and limitations of fMRI for this purpose and suggest ways to
      improve the use of fMRI for developing new therapeutics, with emphasis on
      treatments for anxiety disorders. Fundamentally, pharmacological studies with
      standard psychiatric treatments using standardized behavioral probes during fMRI
      will need to be carried out to determine characteristic brain signatures that
      could be used to predict whether novel compounds are likely to have specific
      therapeutic effects.

PMID- 17436116
TI  - Effects of propagule density and survival strategies on establishment and growth:
      further investigations in the phylloplane fungal model system.
AB  - This work builds on an earlier culture study where we determined that species
      diversity of competing saprotrophic phyllpolane fungi had only a negligible
      effect on the establishment and coexistence of a target fungus, Pestalotia
      vaccinii. Here, we explore preliminary evidence suggesting that spore density is
      a more important contributing factor to colonization and coexistence. We examine
      the influence of propagule density in vitro on establishment and growth of select
      members of the phylloplane of Vaccinium macrocarpon (American cranberry). To
      evaluate the response of the weak pathogen P. vaccinii to changes in competitors
      spore density, we chose saprotrophs from the previous investigation that had the
      greatest inhibitory effect on the establishment of P. vaccinii (Curvularia
      lunata), an intermediate inhibitory effect (Alternaria alternata) and the least
      inhibitory effect (Penicillium sp.). A constant target spore concentration of 50
      viable spores of P. vaccinii was pit against densities of the three individual
      competitors ranging between 12 and 200 spores. As viable propagule density
      increased, establishment and coexistence of P. vaccinii significantly decreased,
      with C. lunata and A. alternata decreasing the growth of P. vaccinii more than
      Penicillium sp. Concomitantly, both C. lunata and Penicillium sp. were not
      significantly affected by overall spore density but were significantly affected
      by the presence of P. vaccinii. A. alternata, on the other hand, was not
      significantly influenced by the presence of P. vaccinii but was significantly
      affected by overall spore density. An in vitro investigation into the effect of
      interspecific competition on mycelial growth suggests how different survival
      strategies and community assembly rules might influence both growth and
      development. Growth of P. vaccinii was significantly less when interacting with
      C. lunata than when interacting with either A. alternata or Penicillium sp.
      Conversely, P. vaccinii had the greatest effect on the growth of C. lunata, less
      of an effect on the growth of A. alternata, and the least effect on Penicillium
      sp.

PMID- 17436117
TI  - Gallstone ileus: diagnosis and management.
AB  - BACKGROUND: Gallstone ileus is a rare complication of cholelithiasis, mostly in
      the elderly. It accounts for 1%-4% of mechanical bowel obstruction and is
      associated with high morbidity and mortality. We present our experience of
      gallstone ileus and discuss current opinion as reported in the literature.
      PATIENTS AND METHODS: A retrospective review was performed of medical records of
      patients in our institution coded for gallstone ileus by the International
      Classification of Diseases (ICD K-563) coding system between January 1998 and
      December 2005. RESULTS: There were 22 patients with mean age of 77 (58-92) years
      and a female to male ratio of 4.5:1. Most patients presented with abdominal pain
      and vomiting, with a median duration of symptoms of 3 (1-28) days. Preoperative
      diagnosis was made in 77% from a combination of plain x-ray, ultrasonography, and
      computed tomography (CT) scans; 86.4% of the patients belonged to ASA class of 3
      or 4. Twenty patients underwent enterolithotomy alone, and two had one-stage
      procedure. The mean size of impacted stones was 3.6 (2.5-4.5) cm, with location
      in the terminal ileum in 17 and jejunum in 5 patients. There were 5 perioperative
      deaths and an episode of cholangitis occurring in one patient 18 months after
      enterolithotomy alone. CONCLUSIONS: Gallstone ileus is a difficult clinical
      entity to diagnose. Unreserved use of imaging techniques can improve diagnostic
      accuracy and speed of therapeutic decision making. Management of gallstone ileus
      must be individualized. The one-stage procedure should be offered only to highly
      selected patients with good cardiorespiratory reserve and with absolute
      indications for biliary surgery at the time of presentation.

PMID- 17436118
TI  - The effect of chlorhexidine and gentian violet on the adherence of Candida spp.
      to urinary catheters.
AB  - Urinary tract infection associated with catheters is the most common infection in
      the hospital environment. The adherence of microorganisms to the surface is a
      determining factor in colonization and infection. Antiseptics such as
      chlorhexidine and gentian violet have been shown to be effective against yeasts,
      as well as having low toxicity and being low-cost. The objective of the present
      study was to evaluate whether prior treatment of siliconized latex urinary
      catheters with antiseptics reduces the adherence of yeasts. Two reference strains
      of C. albicans (ATCC 645448 and ATCC 90028) and six strains isolated from
      catheter, two each of C. albicans, C. tropicalis, and C. parapsilosis, were used.
      An in vitro study of adherence was carried out with previously treated catheters,
      in separate experiments of 1 h and 24 h of incubation under continued shaking.
      The relative hydrophobicity of the cell surface of the yeasts before and after 1
      h of exposure to chlorhexidine was determined. The results demonstrated that both
      treatments were effective in controlling the adherence of yeast to the catheter
      (P < 0.0001), and that the hydrophobicity of the eight strains significantly
      increased after contact with chlorhexidine (P < 0.0001). These results suggest
      that the antimicrobial activity of chlorhexidine and gentian violet reduces the
      adherence of the microorganisms to the catheter.

PMID- 17436119
TI  - Further evidence of nuclear reactions in the Pd/D lattice: emission of charged
      particles.
AB  - Almost two decades ago, Fleischmann and Pons reported excess enthalpy generation
      in the negatively polarized Pd/D-D2O system, which they attributed to nuclear
      reactions. In the months and years that followed, other manifestations of nuclear
      activities in this system were observed, viz. tritium and helium production and
      transmutation of elements. In this report, we present additional evidence,
      namely, the emission of highly energetic charged particles emitted from the Pd/D
      electrode when this system is placed in either an external electrostatic or
      magnetostatic field. The density of tracks registered by a CR-39 detector was
      found to be of a magnitude that provides undisputable evidence of their nuclear
      origin. The experiments were reproducible. A model based upon electron capture is
      proposed to explain the reaction products observed in the Pd/D-D2O system.

PMID- 17436120
TI  - Comparative genomics of xenobiotic metabolism: a porcine-human PXR gene
      comparison.
AB  - The pregnane X receptor (PXR) plays a crucial role in xenobiotic and drug
      metabolism, being the major transcriptional regulator of cytochrome P-450
      monooxygenase 3A4, which metabolizes more than 50% of all clinically used drugs.
      Recent pharmacodynamic studies have shown that the mouse is not an ideal model
      for predicting human clinical drug study outcomes. Therefore, we characterized
      the porcine PXR (pPXR) gene to evaluate the utility of the pig as an alternate
      preclinical animal model. The complete sequence of pPXR mRNA and 11 kb of genomic
      sequence were obtained. Similar to the human PXR gene, the pPXR gene revealed
      multiple splice variants in the ligand-binding domain. All pPXR splice variants
      (SV) were porcine-specific. The pPXR mRNAs varied in 3'-UTR length due to
      differential termination and specific deletions. Northern blot analyses
      identified high levels of pPXR mRNA expression in the liver, small intestine,
      heart, kidney, and colon. RT-PCR amplification detected lower levels of pPXR
      expression in multiple tissues. Ninety-three pigs representing eight breeds were
      analyzed for single nucleotide polymorphisms (SNPs). Only one nonsynonymous SNP
      (S178L) was found in the pPXR ligand-binding domain. This characterization of the
      pPXR gene contributes to the development of a porcine model for human drug
      metabolic studies.

PMID- 17436122
TI  - Predicting stricture in morbidly obese patients undergoing laparoscopic Roux-en-Y
      gastric bypass: a logistic regression analysis.
AB  - Gastrojejunostomy stricture after Roux-en-Y gastric bypass occurs in 3 to 27% of
      morbidly obese patients in the USA. We questioned whether preoperative patient
      characteristics, including demographic attributes and comorbid disease, might be
      significant factors in the etiology of stricture. In this study from November
      2001 to February 2006 (51 months), at a high-volume bariatric center, of the
      1,351 patients who underwent laparoscopic gastric bypass, 92 developed stricture
      (6.8%). All but two were treated successfully by endoscopic dilation. All
      patients stopped nonsteroidal anti-inflammatory medications 2 weeks prior to
      surgery and did not restart them. The operative procedure included the use of a
      21-mm transoral circular stapler to create the gastrojejunostomy; the Roux limb
      was brought retrogastric, retrocolic. In an effort to reduce our center's
      stricture rate, late in the study, U-clips used at the gastrojejunostomy were
      replaced by absorbable sutures, and postoperative H2 antagonists were added to
      the treatment protocol. The change to absorbable polyglactin suture proved to be
      significant, resulting in a lower stricture rate. The addition of H2 antagonists
      showed no significant effect. Following the retrospective review of the
      prospective database, univariate and multivariate logistic regression analyses
      identified factors associated with the development of stricture. Gastroesophageal
      reflux disease and age were each shown to be statistically significant
      independent predictors of stricture following laparoscopic gastric bypass.

PMID- 17436123
TI  - Treatment of gastric adenocarcinoma may differ among hospital types in the United
      States, a report from theNational Cancer Data Base.
AB  - The concept that complex surgical procedures should be performed at high-volume
      centers to improve surgical morbidity and mortality is becoming widely accepted.
      We wanted to determine if there were differences in the treatment of patients
      with gastric cancer between community cancer centers and teaching hospitals in
      the United States. Data from the 2001 Gastric Cancer Patient Care Evaluation
      Study of the National Cancer Data Base comprising 6,047 patients with gastric
      adenocarcinoma treated at 691 hospitals were assessed. The mean number of
      patients treated was larger at teaching hospitals (14/year) when compared to
      community centers (5-9/year) (p<0.05). The utilization of laparoscopy and
      endoscopic ultrasonography were significantly more common at teaching centers
      (p<0.01). Pathologic assessment of greater than 15 nodes was documented in 31% of
      specimen at community hospitals and 38% at teaching hospitals (p<0.01). Adjusted
      for cancer stage, chemotherapy and radiation therapy were utilized with equal
      frequency at all types of treatment centers. The 30-day postoperative mortality
      was lowest at teaching hospitals (5.5%) and highest at community hospitals (9.9%)
      (p<0.01). These data support previous publications demonstrating that patients
      with diseases requiring specialized treatment have lower operative mortality when
      treated at high-volume centers.

PMID- 17436124
TI  - Middle segment pancreatectomy: a useful tool in the management of pancreatic
      neoplasms.
AB  - Small, benign, or low-grade malignant tumors located in the neck of the pancreas
      are usually treated with enucleation. However, if enucleation is too risky
      because of possible damage of the main pancreatic duct, standard pancreatic
      resections are performed. Such operations can lead to impaired long-term exocrine
      endocrine function. Middle segment pancreatectomy consists of a limited resection
      of the midportion of the pancreas and can be performed in selected patients
      affected by tumors of the pancreatic neck. Middle segment pancreatectomy is a
      safe and feasible procedure for treating tumors of the pancreatic neck; in
      experienced hands it is associated with no mortality but with high morbidity,
      even if the rate of "clinical" pancreatic fistula is about 20%. Moreover, it
      allows a surgeon to preserve pancreatic parenchyma and consequently long-term
      endocrine and exocrine pancreatic function.

PMID- 17436125
TI  - An innovative option for venous reconstruction after pancreaticoduodenectomy: the
      left renal vein.
AB  - INTRODUCTION: Pancreatic ductal adenocarcinoma has a high mortality rate with
      limited treatment options. One option is pancreaticoduodenectomy, although
      complete resection may require venous resection. Pancreaticoduodenectomy with
      venous resection and reconstruction is becoming a more common practice with many
      choices for venous reconstruction. We describe the technique of using the left
      renal vein as a conduit for venous reconstruction during pancreaticoduodenectomy.
      METHODS: The technique for use of the left renal vein as an interposition graft
      for venous reconstruction during pancreaticoduodenectomy is described as well as
      outcomes for nine patients that have undergone the procedure. RESULTS: Nine
      patients, seven men, with a mean age of 57 years, have undergone the operation.
      There were eight interposition grafts and one patch graft. Mean operating time
      was 7.8 hours, and mean tumor size was 3.4 cm. Eight patients had node-positive
      disease, and six had involvement of the vein. Mean hospital stay was 14 days and
      perioperative morbidity included a superficial wound infection, delayed gastric
      emptying, ascites, and gastrointestinal bleeding in one patient each. Creatinine
      ranged from 0.8-1.1 mg/dl preoperatively and from 0.7-1.3 mg/dl at discharge.
      Mean follow-up was 6.8 months with normal creatinine values noted through the
      follow-up period. Two patients had died during follow-up from recurrent disease
      at 8.3 and 18.2 months after the operation. CONCLUSIONS: The left renal vein
      provides an additional choice for an autologous graft during
      pancreaticoduodenectomy with venous resection. The ease of harvesting the graft
      and maintenance of renal function distinguish its use.

PMID- 17436126
TI  - Management of massive arterial hemorrhage after pancreatobiliary surgery: does
      embolotherapy contribute to successful outcome?
AB  - Massive arterial hemorrhage is, although unusual, a life-threatening complication
      of major pancreatobiliary surgery. Records of 351 patients who underwent major
      surgery for malignant pancreatobiliary disease were reviewed in this series.
      Thirteen patients (3.7%) experienced massive hemorrhage after surgery. Complete
      hemostasis by transcatheter arterial embolization (TAE) or re-laparotomy was
      achieved in five patients and one patient, respectively. However, 7 of 13 cases
      ended in fatality, which is a 54% mortality rate. Among six survivors, one
      underwent selective TAE for a pseudoaneurysm of the right hepatic artery (RHA).
      Three patients underwent TAE proximal to the proper hepatic artery (PHA): hepatic
      inflow was maintained by successful TAE of the gastroduodenal artery in two and
      via a well-developed subphrenic artery in one. One patient had TAE of the celiac
      axis for a pseudoaneurysm of the splenic artery (SPA), and hepatic inflow was
      maintained by the arcades around the pancreatic head. One patient who experienced
      a pseudoaneurysm of the RHA after left hemihepatectomy successfully underwent re
      laparotomy, ligation of RHA, and creation of an ileocolic arterioportal shunt. In
      contrast, four of seven patients with fatal outcomes experienced hepatic
      infarction following TAE proximal to the PHA or injury of the common hepatic
      artery during angiography. One patient who underwent a major hepatectomy for
      hilar bile duct cancer had a recurrent hemorrhage after TAE of the gastroduodenal
      artery and experienced hepatic failure. In the two patients with a pseudoaneurysm
      of the SPA or the superior mesenteric artery, an emergency re-laparotomy was
      required to obtain hemostasis because of worsening clinical status. Selective TAE
      distal to PHA or in the SPA is usually successful. TAE proximal to PHA must be
      restricted to cases where collateral hepatic blood flow exists. Otherwise or for
      a pseudoaneurysm of the superior mesenteric artery, endovascular stenting,
      temporary creation of an ileocolic arterioportal shunt, or vascular
      reconstruction by re-laparotomy is an alternative.

PMID- 17436127
TI  - Platelet function in acute experimental pancreatitis.
AB  - Acute pancreatitis (AP) is characterized by disturbances of pancreatic
      microcirculation. It remains unclear whether platelets contribute to these
      perfusion disturbances. The aim of our study was to investigate platelet
      activation and function in experimental AP. Acute pancreatitis was induced in
      rats: (1) control (n=18; Ringer's solution), (2) mild AP (n=18; cerulein), and
      (3) severe AP (n=18; glycodeoxycholic acid (GDOC)+cerulein). After 12 h,
      intravital microscopy was performed. Rhodamine-stained platelets were used to
      investigate velocity and endothelial adhesion in capillaries and venules. In
      addition, erythrocyte velocity and leukocyte adhesion were evaluated. Serum
      amylase, thromboxane A2, and histology were evaluated after 24 h in additional
      animals of each group. Results showed that 24 h after cerulein application,
      histology exhibited a mild AP, whereas GDOC induced severe necrotizing AP.
      Intravital microscopy showed significantly more platelet-endothelium interaction,
      reduced erythrocyte velocity, and increased leukocyte adherence in animals with
      AP compared to control animals. Thromboxane levels were significantly elevated in
      all AP animals and correlated with the extent of platelet activation and severity
      of AP. In conclusion, platelet activation plays an important role in acute,
      especially necrotizing, pancreatitis. Mainly temporary platelet-endothelium
      interaction is observed during mild AP, whereas severe AP is characterized by
      firm adhesion with consecutive coagulatory activation and perfusion failure.

PMID- 17436128
TI  - CD24 expression is an independent prognostic marker in cholangiocarcinoma.
AB  - CD24 has been described as an adverse prognostic marker in several malignancies.
      This study evaluates CD24 expression in cholangiocarcinoma and correlates the
      findings with clinicopathologic data and patient survival. Between 1996 and 2002,
      22 consecutive patients with cholangiocarcinoma were treated at our institution.
      Demographic data, SEER stage, pathologic data, treatment, expression of CD24,
      mitogen-activated protein kinase (MAPK), phosphorylated MAPK, and survival were
      analyzed. The majority of the tumors demonstrated CD24 (81.8%) and p-MAPK (87%)
      expression. A negative association was noted between the expression of CD24 and p
      MAPK. Median survival for patients with low expression of CD24 was 36 months and
      high expression was 8 months. Median survival for patients who received
      chemotherapy with low CD24 expression was 163 months, and for seven patients with
      high CD24 expression, it was 17 months (p=0.04). With the addition of radiation
      therapy, median survival for patients with low expression of CD24 was 52 months
      and high expression was 17 months (p=0.08). On multivariate analysis, the use of
      chemotherapy (p=0.0014, hazard ratio 0.069) and the CD24 overexpression (p=0.02,
      hazard ratio 7.528) were predictive of survival. CD24 is commonly expressed in
      cholangiocarcinoma, and overexpression is predictive of poor survival and
      possibly of lack of response to chemotherapy and radiation therapy. These
      findings may improve selection of patients for the appropriate treatment modality
      and the development of CD24-targeted therapy.

PMID- 17436129
TI  - Management of hepatic angiomyolipoma.
AB  - Preoperative diagnosis of hepatic angiomyolipoma is difficult, and the treatment
      for it remains controversial. The aim of this study is to review our experience
      in the treatment of hepatic angiomyolipoma and to propose a treatment strategy
      for this disease. We retrospectively collected the clinical, imaging, and
      pathological features of patients with hepatic angiomyolipoma.
      Immunohistochemical studies with antibodies for HMB-45, actin, S-100,
      cytokeratin, vimentin, and c-kit were performed. Treatment experience and long
      term follow-up results are summarized. During a period of 9 years, 10 patients
      with hepatic angiomyolipoma were treated at our hospital. There was marked female
      predominance (nine patients). Nine patients received surgical resection without
      complications. One patient received nonoperative management with biopsy and
      follow-up. One patient died 11 months after surgery because of recurrent disease.
      We propose all symptomatic patients should receive surgical resection for hepatic
      angiomyolipoma. Conservative management with close follow-up is suggested in
      patients with asymptomatic tumors and meet the following criteria: (1) tumor size
      smaller than 5 cm, (2) angiomyolipoma proved through fine needle aspiration
      biopsy, (3) patients with good compliance, and (4) not a hepatitis virus carrier.

PMID- 17436130
TI  - Liver transplantation across Rh blood group barriers increases the risk of
      biliary complications.
AB  - BACKGROUND: Cold ischemia time and the presence of postoperative hepatic arterial
      thrombosis have been associated with biliary complications (BC) after liver
      transplantation. An ABO-incompatible blood group has also been suggested as a
      factor for predisposal towards BC. However, the influence of Rh nonidentity has
      not been studied previously. MATERIALS: Three hundred fifty six liver transplants
      were performed from 1995 to 2000 at our hospital. BC incidence and risk factors
      were studied in 345 patients. RESULTS: Seventy patients (20%) presented BC after
      liver transplantation. Bile leakage (24/45%) and stenotic anastomosis (21/30%)
      were the most frequent complications. Presence of BC in Rh-nonidentical graft
      host cases (23/76, 30%) was higher than in Rh-identical grafts (47/269, 17%)
      (P=0.01). BC was also more frequent in grafts with arterial thrombosis (9/25, 36%
      vs 60/319, 19%; P=0.03) and grafts with cold ischemia time longer than 430 min
      (26/174, 15% vs 44/171, 26%; P=0.01). Multivariate logistic regression confirmed
      that Rh graft-host nonidentical blood groups [RR=2(1.1-3.6); P=0.02], arterial
      thrombosis [RR=2.6(1.1-6.4); P=0.02] and cold ischemia time longer than 430 min
      [RR=1.8(1-3.2); P=0.02] were risk factors for presenting BC. CONCLUSION: Liver
      transplantation using Rh graft-host nonidentical blood groups leads to a greater
      incidence of BC.

PMID- 17436131
TI  - Does microvascular invasion affect outcomes after liver transplantation for HCC?
      A histopathological analysis of 155 consecutive explants.
AB  - Macroscopic vascular invasion (macroVI) is associated with poor outcomes after
      liver transplantation (LT) for hepatocellular carcinoma (HCC). Whether
      microvascular invasion (microVI) is associated with the same adverse prognosis is
      unclear. One hundred and fifty-five consecutive patients with confirmed HCC after
      LT from March 1991 to 2004 at our institution were reviewed. Patients had to
      satisfy Milan criteria to be accepted for LT. They were followed with
      surveillance images every 3 months while on the waiting list. Disease-free
      survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis.
      Demographic, tumor, and histopathologic characteristics were tested for their
      prognostic significance. Median follow-up after LT was 30 months. Overall graft
      survival rates were 87, 74, and 65% at 1, 3, and 5 years, respectively. All
      recurrences (22/155, 14%) developed within 4 years after LT with an overall 5
      year DFS of 79%. Vascular invasion, either microVI or macroVI, was more likely in
      patients with multicentric HCC (n>or=3, p<0.001) and larger tumor size>4 cm
      (p=0.04). Tumor size>5 cm (p=0.04), advanced pathological TMN stage (p=0.007),
      microVI (p=0.001), and macroVI (p<0.001) predicted poor tumor-free survival on
      univariate analysis, but only macroVI was significant in multivariate analysis
      (hazard ratio 54.2, 95% confidence interval 11, 266). Furthermore, only macroVI
      was a significant predictor of mortality after LT (p=0.01). Macrovascular
      invasion is strongly associated with high rates of recurrence and diminished
      survival after LT whereas microVI is not an independent risk factor.

PMID- 17436132
TI  - The role and limitations of 18-fluoro-2-deoxy-D-glucose positron emission
      tomography (FDG-PET) scan and computerized tomography (CT) in restaging patients
      with hepatic colorectal metastases following neoadjuvant chemotherapy: comparison
      with operative and pathological findings.
AB  - BACKGROUND: Recent data confirmed the importance of 18-fluoro-2-deoxy-D-glucose
      positron emission tomography (FDG-PET) in the selection of patients with
      colorectal hepatic metastases for surgery. Neoadjuvant chemotherapy before
      hepatic resection in selected cases may improve outcome. The influence of
      chemotherapy on the sensitivity of FDG-PET and CT in detecting liver metastases
      is not known. METHODS: Patients were assigned to either neoadjuvant treatment or
      immediate hepatic resection according to resectability, risk of recurrence,
      extrahepatic disease, and patient preference. Two-thirds of them underwent FDG
      PET/CT before chemotherapy; all underwent preoperative contrast-enhanced CT and
      FDG-PET/CT. Those without extensive extrahepatic disease underwent open
      exploration and resection of all the metastases according to original imaging
      findings. Operative and pathological findings were compared to imaging results.
      RESULTS: Twenty-seven patients (33 lesions) underwent immediate hepatic resection
      (group 1), and 48 patients (122 lesions) received preoperative neoadjuvant
      chemotherapy (group 2). Sensitivity of FDG-PET and CT in detecting colorectal
      (CR) metastases was significantly higher in group 1 than in group 2 (FDG-PET:
      93.3 vs 49%, P<0.0001; CT: 87.5 vs 65.3, P=0.038). CT had a higher sensitivity
      than FDG-PET in detecting CR metastases following neoadjuvant therapy (65.3 vs
      49%, P<0.0001). Sensitivity of FDG-PET, but not of CT, was lower in group 2
      patients whose chemotherapy included bevacizumab compared to patients who did not
      receive bevacizumab (39 vs 59%, P=0.068). CONCLUSIONS: FDG-PET/CT sensitivity is
      lowered by neoadjuvant chemotherapy. CT is more sensitive than FDG-PET in
      detecting CR metastases following neoadjuvant therapy. Surgical decision-making
      requires information from multiple imaging modalities and pretreatment findings.
      Baseline FDG-PET and CT before neoadjuvant therapy are mandatory.

PMID- 17436133
TI  - Duodeno-gastric-esophageal reflux--what is pathologic? Comparison of patients
      with Barrett's esophagus and age-matched volunteers.
AB  - INTRODUCTION: The aim of the study was to analyse pH- and bile-monitoring data in
      patients with Barrett's esophagus and in age- and gender-matched controls.
      SUBJECTS AND METHODS: Twenty-four consecutive Barrett's patients (8 females, 16
      males, mean age 57 years), 21 patients with esophagitis (10 females, 11 males,
      mean age 58 years), and 19 healthy controls (8 females, 11 males, mean age 51
      years), were included. Only patients underwent endoscopy with biopsy. All groups
      were investigated with manometry, gastric and esophageal 24-h pH, and
      simultaneous bile monitoring according to a standardized protocol. A bilirubin
      absorption>0.25 was determined as noxious bile reflux. The receiver operator
      characteristic (ROC) method was applied to determine the optimal cutoff value of
      pathologic bilirubin levels. RESULTS: Of Barrett's patients, 79% had pathologic
      acidic gastric reflux (pH<4>5% of total measuring time). However, 32% of healthy
      controls also had acid reflux (p<0.05) without any symptoms. The median of
      esophageal bile reflux was 7.8% (lower quartile (LQ)-upper quartile (UQ)=1.6
      17.8%) in Barrett's patients, in patients with esophagitis, 3.5% (LQ-UQ=0.1
      13.5), and in contrast to 0% (LQ-UQ=0-1.0%) in controls, p=0.001. ROC analysis
      showed the optimal dividing value for patients at more than 1% bile reflux over
      24 h (75% sensitivity, 84% specificity). CONCLUSION: An optimal threshold to
      differentiate between normal and pathological bile reflux into the esophagus is
      1% (24-h bile monitoring with an absorbance>0.25).

PMID- 17436134
TI  - The extended learning curve for laparoscopic fundoplication: a cohort analysis of
      400 consecutive cases.
AB  - Many studies have looked at the learning curve associated with laparoscopic
      Nissen fundoplication (LNF) in a given institution. This study looks at the
      learning curve of a single surgeon with a large cohort of patients over a 10-year
      period. Prospective data were collected on 400 patients undergoing laparoscopic
      fundoplication for over 10 years. The patients were grouped consecutively into
      cohorts of 50 patients. The operating time, the length of postoperative hospital
      stay, the conversion rate to open operation, the postoperative dilatation rate,
      and the reoperation rate were analyzed. Results showed that the mean length of
      operative time decreased from 143 min in the first 50 patients to 86 min in the
      last 50 patients. The mean postoperative length of hospital stay decreased from
      3.7 days initially to 1.2 days latterly. There was a 14% conversion to open
      operation rate in the first cohort compared with a 2% rate in the last cohort.
      Fourteen percent of patients required reoperation in the first cohort and 6% in
      the last cohort. Sixteen percent required postoperative dilatation in the first
      cohort. None of the last 150 patients required dilatation. In conclusion,
      laparoscopic fundoplication is a safe and effective operation for patients with
      gastroesophageal reflux disease. New techniques and better instrumentation were
      introduced in the early era of LNF. The learning curve, however, continues well
      beyond the first 20 patients.

PMID- 17436135
TI  - Impact of solitary involved lymph node on outcome in localized cancer of the
      esophagus and esophagogastric junction.
AB  - Node-positive esophageal cancer is associated with a dismal prognosis. The impact
      of a solitary involved node, however, is unclear, and this study examined the
      implications of a solitary node compared with greater nodal involvement and node
      negative disease. The clinical and pathologic details of 604 patients were
      entered prospectively into a database from1993 and 2005. Four pathologic groups
      were analyzed: node-negative, one lymph node positive, two or three lymph nodes
      positive, and greater than three lymph nodes positive. Three hundred and fifteen
      patients (52%) were node-positive and 289 were node-negative. The median survival
      was 26 months in the node-negative group. Patients (n=84) who had one node
      positive had a median survival of 16 months (p=0.03 vs node-negative). Eighty
      four patients who had two or three nodes positive had a median survival of 11
      months compared with a median survival of 8 months in the 146 patients who had
      greater than three nodes positive (p=0.01). The survival of patients with one
      node positive [number of nodes (N)=1] was also significantly greater than the
      survival of patients with 2-3 nodes positive (N=2-3) (p=0.049) and greater than
      three nodes positive (p<0001). The presence of a solitary involved lymph node has
      a negative impact on survival compared with node-negative disease, but it is
      associated with significantly improved overall survival compared with all other
      nodal groups.

PMID- 17436136
TI  - Factors affecting morbidity and mortality of Roux-en-Y gastric bypass for
      clinically severe obesity: an analysis of 1,000 consecutive open cases by a
      single surgeon.
AB  - INTRODUCTION: Determinants of perioperative risk for RYGB are not well defined.
      METHODS: Retrospective analysis of comorbidities was used to evaluate predictors
      of perioperative risk in 1,000 consecutive patients having open RYGB by
      univariate analyses and logistic regression. RESULTS: One hundred forty-six men,
      854 women; average age 38.3+/-11.2 years; mean BMI 51.8+/-10.5 (range 24-116)
      were evaluated. Average hospital stay (LOS) was 3.8 days; 87%<3 days. 91.3% of
      procedures were without major complication. The most common complications were
      incisional hernia 3.5%, intestinal obstruction 1.9%, and leak 1.6%. 31 patients
      required reoperation within 30 days (3.1%). A 30-day mortality was 1.2%. Logistic
      regression evaluating predictors of operative mortality correlated strongly with
      coronary artery disease (CAD) (p<0.01), sleep apnea (p=0.03), and age (p=0.042).
      BMI>50 (0.6 vs 2.3%, p=0.03) and male sex were associated with increased
      mortality (1.3 vs. 4.0%, p=0.02). Sex-specific logistic regression demonstrated
      males with angiographically proven CAD were more likely to die (p=0.028) than
      matched cohorts. Age (p=0.033) and sleep apnea (p=0.040) were significant
      predictors of death for women. CONCLUSION: Perioperative mortality after RYGB
      appears to be affected by sex, BMI, age, CAD, and sleep apnea. Strategies
      employing risk stratification should be developed for bariatric surgery.

PMID- 17436137
TI  - Intestinal perforations in Behcet's disease.
AB  - Behcet's disease accompanied by intestinal involvement is called intestinal
      Behcet's disease. The intestinal ulcers of Behcet's disease are usually multiple
      and scattered and tend to perforate easily, so that many patients require
      emergency operation. The aim of this study is to determine the extent of surgical
      resection necessary to prevent reperforation and to point out the findings of
      concurrent oral and genital ulcers and multiple intestinal perforations in all
      patients of our series. During a 25-year study period, information of 125
      Behcet's disease cases was gathered. Among the 82 patients who were diagnosed
      with intestinal Behcet's disease, 22 cases had intestinal perforations needing
      emergency laparotomy. We investigated and analyzed these cases according to the
      patients' demographic characteristics, clinical presentations, laboratory data,
      and surgical outcome. There were 14 men and 8 women ranging from 22 to 65 years
      of age. Nine cases were diagnosed preoperatively, and the diagnoses were
      confirmed in all 22 cases during the surgical intervention. Surgical resection
      was performed in every patient, with right hemicolectomy and ileocecal resection
      in 11 cases, partial ileum resection in 8 cases with two reperforations, and
      ileocecal resection in 3 cases with one reperforation.

PMID- 17436138
TI  - Acquiring tetanus after hemorrhoid banding and other gastrointestinal procedures.
AB  - Tetanus after hemorrhoidal banding is an extremely rare but serious complication
      of the procedure. We describe the second reported case of this complication and
      review the literature concerning tetanus after different gastrointestinal
      procedures. Although a rare complication, practicing physicians need to be aware
      of the clinical presentation of this deadly disease when encountered in at-risk
      patient populations. Such cases also reemphasize the importance of primary
      tetanus immunization and follow-up boosters for all vulnerable patients.

PMID- 17436139
TI  - Bromodeoxyuridine labeling index as an indicator of early tumor response to
      preoperative radiotherapy in patients with rectal cancer.
AB  - PURPOSE: Assessment of tumor proliferation rate using Bromodeoxyuridine labeling
      index (BrdUrdLI) as a possible predictor of rectal cancer response to
      preoperative radiotherapy (RT). METHODS AND MATERIAL: Ninety-two patients were
      qualified either to short RT (5 Gy/fraction/5 days) and surgery about 1 week
      after RT (schedule I), or to short RT and 4-5 weeks interval before surgery
      (schedule II). Tumor samples were taken twice from each patient: before RT and at
      the time of surgery. The samples were incubated with BrdUrd for 1 h at 37 degrees
      C, and the BrdUrdLI was calculated as a percentage of BrdUrd-labeled cells.
      RESULTS: Thirty-eight patients were treated according to schedule I and 54
      patients according to schedule II. Mean BrdUrdLI before RT was 8.5% and its value
      did not differ between the patients in the two compared groups. After RT tumors
      showed statistically significant growth inhibition (reduction of BrdUrdLI). As
      the pretreatment BrdUrd LI was not predictive for early clinical and pathologic
      tumor response, prognostic role of the ratio of BrdUrdLI after to BrdUrdLI before
      RT was considered. The ratios were calculated separately for fast (BrdUrd
      LI>8.5%) and slowly (BrdUrd LI<or=8.5%) proliferating tumors and correlated with
      overall treatment time (OTT, i.e., time from the first day of RT to surgery). One
      month after RT, accelerated proliferation was observed only in slowly
      proliferating tumors. CONCLUSIONS: Pretreatment BrdUrdLI was not predictive for
      early clinical and pathologic tumor response. The ratio after/before RT BrdUrdLI
      was correlated to inhibition of proliferation in responsive tumors.

PMID- 17436140
TI  - Risk of fecal diversion in complicated perianal Crohn's disease.
AB  - The purpose of the study was to determine the overall risk of a permanent stoma
      in patients with complicated perianal Crohn's disease, and to identify risk
      factors predicting stoma carriage. A total of 102 consecutive patients presented
      with the first manifestation of complicated perianal Crohn's disease in our
      outpatient department between 1992 and 1995. Ninety-seven patients (95%) could be
      followed up at a median of 16 years after first diagnosis of Crohn's disease.
      Patients were sent a standardized questionnaire and patient charts were reviewed
      with respect to the recurrence of perianal abscesses or fistulas and surgical
      treatment, including fecal diversion. Factors predictive of permanent stoma
      carriage were determined by univariate and multivariate analysis. Thirty of 97
      patients (31%) with complicated perianal Crohn's disease eventually required a
      permanent stoma. The median time from first diagnosis of Crohn's disease to
      permanent fecal diversion was 8.5 years (range 0-23 years). Temporary fecal
      diversion became necessary in 51 of 97 patients (53%), but could be successfully
      removed in 24 of 51 patients (47%). Increased rates of permanent fecal diversion
      were observed in 54% of patients with complex perianal fistulas and in 54% of
      patients with rectovaginal fistulas, as well as in patients that had undergone
      subtotal colon resection (60%), left-sided colon resection (83%), or rectal
      resection (92%). An increased risk for permanent stoma carriage was identified by
      multivariate analysis for complex perianal fistulas (odds ratio [OR] 5; 95%
      confidence interval [CI] 2-18), temporary fecal diversion (OR 8; 95% CI 2-35),
      fecal incontinence (OR 21, 95% CI 3-165), or rectal resection (OR 30; 95% CI 3
      179). Local drainage, setons, and temporary stoma for deep and complicated
      fistulas in Crohn's disease, followed by a rectal advancement flap, may result in
      closing of the stoma in 47% of the time. The risk of permanent fecal diversion
      was substantial in patients with complicated perianal Crohn's disease, with
      patients requiring a colorectal resection or suffering from fecal incontinence
      carrying a particularly high risk for permanent fecal diversion. In contrast,
      patients with perianal Crohn's disease who required surgery for small bowel
      disease or a segmental colon resection carried no risk of a permanent stoma.

PMID- 17436141
TI  - Successful internalization of a chronic biliary cutaneous fistula after liver
      transplantation: deepithelializing the fistula tract.
AB  - Biliary cutaneous fistulas are uncommon sequelae after biliary surgery and can be
      a source of significant morbidity. We describe a liver recipient who developed a
      biliary cutaneous fistula secondary to hepatic artery thrombosis; this
      subsequently drained for over 7 years. Through a novel approach, using the
      transabdominal fistula tract as a conduit, the fistula skin opening was
      deepithelialized and anastomosed to a jejunal loop, internally draining the
      tract. For over 7 years postoperatively, this internal drainage procedure has
      continued to function effectively. This approach may have value in internalizing
      longstanding biliary cutaneous fistulas in well-selected patients in whom there
      is no existing biliary ductal system or the existing system anatomically does not
      lend itself to restoration of functional internal drainage through conventional
      approaches.

PMID- 17436143
TI  - Hemangiopericytoma of the greater omentum.
AB  - A 41-year-old Chinese woman was admitted to our hospital with epigastric pain.
      Computed tomography detected a heterogeneous enhancement tumor fed by the left
      gastroepiploic artery in the left lower quadrant and cholelithiasis. Excision of
      the tumor in the greater omentum and cholecystectomy were performed
      laparoscopically. Histological findings confirmed a diagnosis of
      hemangiopericytoma with low-grade malignancy. To our knowledge,
      hemangiopericytoma of the greater omentum is very rare, and only 12 cases were
      reported in English literature. We report a case of hemangiopericytoma arising in
      the greater omentum and review the literature.

PMID- 17436142
TI  - Controversies in the surgical management of sigmoid diverticulitis.
AB  - The timing and appropriateness of surgical treatment of sigmoid diverticular
      disease remain a topic of controversy. We have reviewed the current literature on
      this topic, focusing on issues related to the indications and types of surgery.
      Current evidence would suggest that elective surgery for diverticulitis can be
      avoided in patients with uncomplicated disease, regardless of the number of
      recurrent episodes. Furthermore, the need for elective surgery should not be
      influenced by the age of the patient. Operation should be undertaken in patients
      with severe attacks, as determined by their clinical and radiological evaluation.

PMID- 17436144
TI  - Prevalence and clinical significance of elevated antinuclear antibody test in
      children and adult patients with idiopathic thrombocytopenic purpura.
AB  - BACKGROUND: To determine the clinical significance of the antinuclear antibody
      (ANA) test in children and adult patients with idiopathic thrombocytopenic
      purpura (ITP). METHOD: We conducted a retrospective analysis of 365 children and
      108 adult patients with ITP. Patients found to have positive ANA were regularly
      followed-up by an experienced hematologist until December 2006 for development of
      symptoms indicative of autoimmune disorder. Mean follow-up 3.6 years (range: 2.1
      7 years) for all patients. At the time of diagnosis of ITP, patients with
      connective tissue diseases (CTD) were excluded. Out of 365 childhood ITP; 301
      (82.4%) patients were acute, 64 (17.6%) patients were chronic ITP. ANA titer > or
      = 1:80 were positive in 33 (9.04%) of 365 patients with childhood ITP; 21
      patients (6.9%) were in acute, and 12 patients (18.7%) were in chronic group. Out
      of 108 adult patients with ITP; 31 (28.7%) patients were acute and 77 (71.3%)
      patients were chronic ITP cases. ANA titer > or = 1:80 were positive in 36
      (33.3%) of 108 patients with adult ITP; 12 patients (38.8%) were in acute, and 24
      patients (31.2%) were in chronic group. At the end of follow-up period Sjogren's
      syndrome (SS) was diagnosed in only one adult chronic ITP cases. None of the
      other ANA positive patients developed SLE or other CTD. CONCLUSIONS: Our data
      demonstrated that ANA positivity is often found in adult and children patients
      with ITP, and indicate that the detection of ANA positivity is not enough to
      identify those patients with ITP who are at risk of developing SLE or other CTD.
      There is a statistically significant difference in terms of ANA positivity
      between childhood acute and chronic ITP patients. We think that ANA positivity
      may be an indicator in terms of chronicity for childhood ITP. However, large
      scale studies should be considered to determine the significance of ANA
      positivity and their utility in differentiating acute from chronic ITP.

PMID- 17436145
TI  - Risk assessment of atrazine polluted farmland and drinking water: a case study.

PMID- 17436146
TI  - Dietary fatty acid composition differently influences retinoylation reaction in
      rat testes mitochondria.
AB  - All-trans-retinoic acid (atRA) is incorporated covalently into proteins of rat
      testes mitochondria. In this study, the effect of three diets with different
      fatty acid composition on the retinoylation of proteins of rat testes
      mitochondria has been investigated. Different groups of rats were fed on a basal
      diet supplemented with 15% of either coconut oil (CO), olive oil (OO) or fish oil
      (FO). We found that, when compared with CO, the binding of retinoic acid was
      decreased in FO- and OO-fed rats. Mitochondrial phospholipids composition was
      differently influenced by dietary treatments; minor changes were observed in
      fatty acid composition of phospholipids. Few differences were observed in the
      Arrhenius plots among the three groups of rats. Kinetic analysis revealed a
      decrease in the V (max) value in FO- and OO- as compared with CO-fed rats. No
      difference among the three groups were observed in the K ( M ) value. The
      retinoylation reaction was inhibited by 13-cis-RA and 9-cis-RA.

PMID- 17436147
TI  - Mitochondrial function plasticity in Acanthamoeba castellanii during growth in
      batch culture.
AB  - The alterations in mitochondrial bioenergetics during growth in a batch culture
      of Acanthamoeba castellanii were studied. The capacity of cytochrome pathway
      dependent respiration measured in vitro decreased from the intermediary phase,
      when cell division slowed down. The pattern of the cytochrome pathway capacity
      changes was paralleled from the intermediary phase by alterations in the amount
      of total (and reducible) membranous ubiquinone. These changes were accompanied by
      a decrease in mitochondrial reactive oxygen species production in vitro (when no
      energy-dissipating system was active), and almost no change in superoxide
      dismutase activity and protein level, thus indicating an equivalent need for this
      enzyme in oxidative stress defence in A. castellanii culture. On the other hand,
      a decrease in the activity and protein level of alternative oxidase and
      uncoupling protein was observed in vitro, when cells shifted from the exponential
      growth phase to the stationary phase. It turned out that the contribution of both
      energy-dissipating systems in the prevention of mitochondrial reactive oxygen
      species generation in vivo could lead to its constant level throughout the growth
      cycle of A. castellanii batch culture. Hence, the observed functional plasticity
      insures survival of high quality cysts of A. castellanii cells.

PMID- 17436149
TI  - Comparative toxicity of hydrophobic contaminants to microalgae and higher plants.
AB  - To enable rapid and sensitive screening of phytotoxic compounds in terrestrial
      system, a 4 day solid-phase microalgal bioassay was developed. Three species of
      microalgae (Selenastrum capricornutum, Chlorococcum hypnosporum and Chlorococcum
      meneghini) were chosen to investigate their responses to DDTs (DDT, DDD and DDE)
      and PAHs (naphthalene, phenanthrene and pyrene) spiked sands. The bioassay
      results showed that PAHs and DDTs were toxic to microalgae in a 4-day exposure
      tests but not to seed germination of ryegrass (Lolium perenne). Phenanthrene was
      the most phytotoxic. Among three investigated endpoints, fluorescence emissions
      by microalgae were less sensitive than cell density (optical density OD(650)) and
      chlorophyll a concentration as endpoints. In general, S. capricornutum was the
      most sensitive species for PAHs (EC(50) for phenanthrene = 9.4 mg kg(-1)), while
      C. meneghini for DDTs (EC(50) for DDE = 20.0 mg kg(-1)). Comparison of the
      microalgal tests with US EPA standard seed germination/root elongation test
      (using Lolium perenne) demonstrated the superior screening potential of
      phytotoxic hydrophobic compounds using the proposed bioassay. Using OD(650) as
      the endpoint, EC(10) of selected microalgae for PAHs and DDTs were 0.43-64.3 mg
      kg(-1) and 0.67-117 mg kg(-1) respectively, which were much lower than the EC(10)
      of L. perenne for both PAHs (94-187 mg kg(-1)) and DDTs (113-483 mg kg(-1)). The
      results encourage further studies involving wider types of vascular plants and
      more comparison with standard phytotoxicity tests from different authorities
      using contaminated soils to verify the effectiveness of the microalgal bioassay.

PMID- 17436150
TI  - Evaluation of desmin activity using immunohistochemical and immunofluorescent
      staining of myocardial biopsies in patients with chronic heart failure.
      Comparison of the two methods.
AB  - BACKGROUND: Desmin plays one of the key roles in cardiomyocytes. The protein
      protects the integration of the cell and has the following actions: mechanical,
      structural and regulatory. Observed abnormalities of its activity have been
      associated with worsening of heart failure (HF). AIM: Evaluation of desmin
      activity detected with immunohistochemical (IHC) and immunofluorescent (IF)
      staining in cardiomyocytes in patients with chronic HF. METHODS: The study
      population comprised 37 patients (mean age 46.5+/-15.28 years, 83.8% males) with
      diagnosed HF of unknown aetiology, who underwent myocardial biopsy. Coronary
      angiography was performed to exclude presence of significant coronary artery
      disease. Heart failure was diagnosed based on clinical assessment and
      echocardiography showing left ventricular ejection fraction below 45%. RESULTS:
      The IHC and IF evaluation of cardiomyocyte desmin showed that these methods were
      consistent with respect to classification of 31 specimens (83.8%), while being
      discrepant in 6 (16.2%) cases. Desmin detection in myocardial biopsy specimens
      with IHC staining showed normal amounts of this protein in 11 (29.8%) cases,
      excess in 18 (48.6%) patients and deficiency in 8 (21.6%) cases, whereas in IF
      stained specimens respective values were 12 (32.4%), 15 (40.6%) and 10 (27%). No
      significant differences were found between all desmin groups (i.e. normal level,
      excessive and deficiency) evaluated with IHC and IF staining (p=0.39; p=0.25;
      p=0.31, respectively). CONCLUSIONS: The IHC and IF methods allow evaluation of
      desmin activity in cardiomyocytes and division into three types of expression.
      Both methods have high consistency. The IHC, which is the more available method,
      seems to be a sufficient assay.

PMID- 17436151
TI  - CD14 gene polymorphism 159C/T in a group of patients with coronary artery disease
      from a population with high morbidity of cardiovascular diseases.
AB  - BACKGROUND: A role of CD14 receptor in the inflammatory response is stimulation
      of monocytes and endothelial cells by lipopolysaccharide of Gram-negative
      bacteria. The reports about association of progression of atherosclerosis with
      CD14 gene polymorphism in different populations are conflicting. AIM: To assess
      if T to C exchange at position 159 of the CD14 gene correlates with age at the
      onset of first myocardial infarction (MI), severity of coronary atherosclerosis
      and number of risk factors in MI survivors in a local community characterised by
      high morbidity of cardiovascular diseases and whether this genotyping could be
      helpful in identifying patients with a high risk of MI at young age and beyond
      low number of risk factors. METHODS: Fifty-seven MI survivors (75.5% males) from
      98 consecutive patients (pts) with coronary artery disease were included. The
      genotypes in position 159 of the CD14 gene were determined by polymerase chain
      reaction. The medical history concerning diabetes mellitus, arterial
      hypertension, dyslipidaemia, smoking and obesity was taken from every
      participant. Gensini score (GS) was calculated on the basis of coronarography.
      Age at first MI, value of GS and number of risk factors were analysed variables.
      The pts were divided into the decades of life, according to cumulated number of
      risk factors and into the terciles according to GS. Distribution of ages at first
      MI, pts with different number of risk factors and percent of pts belonging to
      determined terciles of GS were compared between subgroups with genotype CC and
      CT, TT. RESULTS: The CC genotype was detected in 25 (43.8%) pts, CT in 30 (52.6%)
      and TT in 2 (3.6%). Age at first MI ranged from 40 to 75 years, mean 58.7+/-7.23,
      values of GS ranged from 0 to 154, mean 48.6+/-25.7, and number of risk factors
      from 0 to 4, mean 1.92+/-0.99. No significant differences in distribution of ages
      at first MI, values of GS or number of risk factors were found between patients
      with CC and with CT or TT genotype in position 159 of CD14 receptor genotype.
      CONCLUSION: These data indicate that screening for CD14 159C/T polymorphism is
      unlikely to be a useful tool for risk assessment of MI at young age,
      independently of low number of risk factors, in a population with high morbidity
      from cardiovascular diseases.

PMID- 17436152
TI  - Pulmonary thromboembolism in 102 consecutive patients with chronic atrial
      fibrillation. Diagnostic value of echocardiography.
AB  - BACKGROUND: Little is known about the incidence and diagnosis of pulmonary
      thromboembolism (PE) in patients with chronic permanent atrial fibrillation
      (CAF). Also it has not been established if echocardiography, a diagnostic tool
      useful in clinical evaluation of both diseases, is of value in diagnosis of PE in
      CAF patients. AIM: To establish the prevalence of PE among patients suffering
      from CAF without or with poorly controlled anticoagulation as well as to evaluate
      the possibility to detect PE and to assess the diagnostic role of
      echocardiography. METHODS: Prevalence of PE in a population of 102 patients (52
      males and 50 females at the mean age of 68 years, range 32-88 years) admitted to
      hospital between January and December 2004 with diagnosis of CAF was studied
      retrospectively. Echocardiography-based original algorithm of PE diagnosis in
      such patients was analysed. RESULTS: Among 102 patients with CAF, 20 (19%) cases
      of PE were diagnosed, including 12 with acute PE (APE) and 8 suffering from
      chronic thromboembolic pulmonary hypertension (CTEPH). Patients with CAF and APE
      as well as with CAF and CTEPH had increased right ventricular dimension (p=0.0002
      and p=0.001, respectively), higher tricuspid pressure gradient (p=0.005 and
      p=0.001, respectively) and shorter pulmonary artery acceleration time (p=0.00006
      and p=0.0004, respectively) estimated in echocardiography as compared to patients
      with CAF but without PE. Subjects with CAF and PE had also significantly
      decreased left ventricular dimension and better left ventricular performance.
      CONCLUSIONS: A relatively high incidence of PE among patients with CAF not
      treated with anticoagulants or with poorly controlled anticoagulation therapy was
      noted. The important value of a diagnostic algorithm employing echocardiography
      in a diagnosis of clinically significant APE and CTEPH in this group of patients
      was also shown.

PMID- 17436153
TI  - Usefulness of early dobutamine stress echocardiography for the assessment of risk
      of restenosis after percutaneous coronary interventions.
AB  - BACKGROUND: The increasing role of percutaneous coronary interventions (PCI) in
      the treatment of coronary artery disease and relatively high restenosis rate
      following PCI require the introduction of available, easy to perform and cost
      effective tests that would enable detection of restenosis after PTCA and
      identification of patients at particularly high risk of restenosis. AIM: To
      estimate the predictive value of early dobutamine stress echocardiography (DSE)
      for the assessment of risk of coronary restenosis. METHODS: Thirty-nine patients
      with a single coronary vessel disease after PCI were enrolled in this study. DSE
      was performed twice--2 to 3 days after the procedure and repeated after 8 to 12
      months. All patients underwent coronary angiography after one-year follow-up.
      RESULTS: Data analysis of direct pre- and postprocedural echocardiography showed
      that the wall motion score index decreased significantly (p <0.0001), whereas
      ejection fraction increased significantly after the intervention when compared
      with baseline (p <0.0001). Restenosis was detected in 8 out of 10 subjects with
      positive DSE test and in 3 out of 29 subjects with negative DSE test. In a group
      of 11 patients with restenosis confirmed in the coronary angiography, one-year
      follow-up DSE was found positive in 9 patients (80% test sensitivity) but in two
      cases results were false negative. Negative test was observed in 27 out of 28
      individuals without restenosis (90% test specificity). CONCLUSIONS: DSE is highly
      sensitive and specific in prediction and detection of restenosis after PCI. DSE
      performed early after PCI is safe.

PMID- 17436154
TI  - Comparison of the exercise treadmill test and 24-hour ECG Holter monitoring in
      patients with syndrome X or coronary atherosclerosis.
AB  - BACKGROUND: Typical chest pain and ECG changes suggest the presence of myocardial
      ischaemia in cardiac syndrome X (SX) patients and resemble the symptoms observed
      in subjects with atherosclerotic coronary artery disease (CAD). AIM: To compare
      the results of exercise treadmill tests (ETT), 24-hour ECG recordings and
      echocardiography in SX and CAD patients without previous myocardial infarction
      with the presence of significant lumen stenosis in one (CA1), two (CA2) or three
      (CA3) coronary arteries. METHODS: Two hundred six patients were included in the
      study: 43 SX (28 female), 49 CA1 (11 female), 51 CA2 (7 female) and 63 CA3
      patients (8 female) all of whom underwent ETT according to the Bruce protocol, 24
      hour ECG recordings and echocardiography. RESULTS: SX patients had median ST
      segment depression during ETT comparable to that in CA1 and CA2 patients but
      significantly less than the CA3 subjects (p=0.024). Median time to ST depression
      of at least 1 mm, as well as median time of exercise, was significantly longer in
      SX individuals than in all CAD patients. The post-exercise recovery time of ST
      segment changes was significantly longer in SX patients than in the CA1 group
      (p=0.006), comparable to that in CA2 subjects and shorter than that in CA3
      individuals (p=0.003). Both the maximal ST-segment depression and the duration of
      significant ST-segment depression in Holter ECG recordings were significantly
      higher in SX patients than in CA1 subjects, were comparable to the values
      observed in the CA2 group and significantly lower than in CA3 individuals. The
      heart rate variability parameters (SDNN and pNN50) were significantly higher in
      SX patients than in CAD subjects. Patients with SX had a significantly thinner
      interventricular septum and smaller left ventricular end-diastolic cavity
      dimension than individuals from the CA1, CA2 and CA3 groups. There were no
      significant differences in the left ventricular ejection fraction or the
      thickness of the left ventricular posterior wall between SX patients and CAD
      patients. CONCLUSIONS: Analysis of the ST segment in SX patients suggests the
      presence of advanced CAD. However, SX patients have better heart rate variability
      and exercise performance than patients with CAD.

PMID- 17436155
TI  - Percutaneous valve repair for mitral regurgitation using the Carillon Mitral
      Contour System. Description of the method and case report.
AB  - Mitral regurgitation may result from left ventricular dilatation and cause
      progression of heart failure. Percutaneous techniques for mitral valve repair are
      under development. Techniques utilizing a trans-coronary venous approach exploit
      the anatomical relationship between the mitral annulus and the venous system of
      the heart. The coronary sinus, great cardiac vein and the origin of the anterior
      interventricular vein surround the posterior mitral annulus. This enables
      percutaneous approaches to annuloplasty for mitral regurgitation. Devices can be
      implanted into the coronary veins that modify the shape and size of the mitral
      annulus. We present a case of ischaemic mitral regurgitation successfully treated
      by use of a percutaneous approach, the Carillon Mitral Contour System.
      Significant reduction of the mitral regurgitation jet was observed. The patient
      was discharged 4 days after the procedure. During the follow-up visits, the
      patient showed an improved general condition and increased exercise capacity.
      Procedural steps are shown in detail and the current status of the coronary sinus
      based technique is discussed. Percutaneous techniques for mitral valve repair may
      be an attractive alternative to cardiac surgery in heart failure patients with
      secondary mitral regurgitation. The Carillon Mitral Contour System is under
      ongoing clinical evaluation in the AMADEUS trial.

PMID- 17436156
TI  - [Acute myocardial infarction in a patient with iatrogenic thyrotoxicosis--a case
      report].
AB  - We present a patient with myocardial infarction and normal coronary angiogram.
      The patient had no classical coronary risk factors, but had thyrotoxicosis, which
      was taken into consideration as a possible cause of myocardial infarction.

PMID- 17436157
TI  - [Severe nonthrombotic pulmonary embolism due to primary cancer of the pancreas--a
      case report].
AB  - We describe a patient with a severe, neoplastic pulmonary embolism due to primary
      cancer of the pancreas. The 40-year-old male was admitted to the haematology
      department with an initial diagnosis of lymphoma. Transthoracic echocardiography
      showed a mass in the right atrium. Transoesophageal echocardiography was
      performed and revealed two moving tumours: the first in the extend of the vena
      cava superior and the second one in the tricuspid valve annulus. After
      bronchoscopy the patient's haemodynamic condition deteriorated and was followed
      by cardiac arrest. Post-mortem examination showed extensive tumour emboli in the
      left pulmonary artery as well as pancreatic cancer at an advanced stage.

PMID- 17436158
TI  - [Angioplasty of the unprotected left main coronary artery stenosis with standby
      cardiopulmonary support--a case report].
AB  - Stenosis of the unprotected left main coronary artery (LMCA) is a classical
      indication for coronary artery bypass graft surgery (CABG). Percutaneous coronary
      intervention (PCI) of LMCA may be an alternative to surgical treatment if
      atherosclerosis of distal segments is very advanced. The periprocedural risk is
      high, especially if comorbidities are present. However, long-term results remain
      unclear. The ongoing Syntax trial will clarify whether angioplasty of LMCA with
      drug-eluting stents can be equivalent to CABG. We present a case of a patient
      with occluded right coronary artery, severe stenoses of the LMCA, left anterior
      descending artery and left circumflex artery, and poor left ventricular ejection
      fraction in whom PCI for stenosis of unprotected LMCA with standby
      cardiopulmonary support was performed.

PMID- 17436159
TI  - [Recent myocardial infarction, cardiogenic shock and unsuccessful coronary
      angioplasty--the pattern of cooperation between a centre without on-site surgical
      back-up and a distantly located clinical cardiosurgery centre].
AB  - The case of a 66-year-old male with acute myocardial infarction (AMI) complicated
      by cardiogenic shock is presented. Because of failed primary PCI, after
      stabilisation of ischaemia and haemodynamics by medication and IABP he was
      transferred to a distantly located cardiosurgery unit. This patient underwent
      successful emergency CABG on the second day after infarction. The problem of
      transporting a patient with AMI and cardiogenic shock to a distant site and the
      problem of emergency CABG in such high-risk patients is discussed.

PMID- 17436160
TI  - [Beta-adrenergic receptors in normal and failing heart].

PMID- 17436161
TI  - [Desmin--an important structural protein of a cardiac myocyte].

PMID- 17436162
TI  - [Simple ventricular ectopy--is it really simple?].

PMID- 17436163
TI  - [Double orifice mitral valve--echocardiographic description].

PMID- 17436164
TI  - [Restenosis and progression of coronary atherosclerosis in the patient with
      coronary artery disease treated by coronary angioplasty with stent implantation].

PMID- 17436165
TI  - [Ablation of a catecholaminergic polymorphic VT and VF originating from Purkinje
      fibers--a case report].
AB  - We describe a case of a 25-year-old woman suffering from recurrent adrenergic
      polymorphic ventricular tachycardia (PVT). As a 14-year-old the patient suffered
      from recurrent episodes of syncope during exercise or emotion. On Holter
      monitoring unsustained runs of PVT were observed. The patient survived SCD (VF)
      which occurred near the hospital. An ICD was implanted and during the first year
      over 150 adequate discharges were present. During 9 year follow-up the patient
      had to have 4 ICDs replaced. She suffered from post-traumatic stress disorder
      syndrome due to frequent ICD shocks. After age of 23 she was admitted to our
      hospital and an ablation using the CARTO system was performed. No low voltage
      areas were observed. During the study ventricular premature beats and VT/PVT runs
      were observed originating from the Purkinje fibres. RF applications were
      delivered at those sites, during which abrupt PVT runs were present. After the
      ablation no ventricular arrhythmia was registered in the ICD memory during 2-year
      follow-up.

PMID- 17436166
TI  - National Disabled Veterans Winter Sports Clinic.

PMID- 17436167
TI  - Sport science in the Paralympic movement.

PMID- 17436168
TI  - Balance problems after unilateral lateral ankle sprains.
AB  - Abstract-Ankle ligament injury is the most common injury in athletic activities.
      This study examined balance problems in athletes with acute lateral ankle
      sprains. Thirty male athletes aged 20 to 35 years with right dominant side and
      traumatic ankle sprain were recruited through simple nonprobability sampling. We
      measured the sway index and limits of stability with the Biodex Balance System
      under different conditions. Functional balance was evaluated with two clinical
      tests: the Functional Reach Test and the Star-Excursion Balance Test. The results
      showed that balance ability in patients with acute lateral ankle sprain was
      significantly weaker under closed- versus open-eye conditions. Symmetry of weight
      bearing on involved and sound limb in bilateral standing was not significantly
      different, but weight-bearing on the nondominant limb was significantly higher
      than on the dominant limb. We can conclude that balance problems occur after
      acute ankle sprains because of proprioception deficits and that the unconscious
      (reflexive) aspect of proprioception is more severely affected than the conscious
      (voluntary) aspect.

PMID- 17436169
TI  - Differences in cause of death of Washington State veterans who did and did not
      use Department of Veterans Affairs healthcare services.
AB  - Relatively little is known about the cause of death in the veteran population,
      although more is known about the cause of death in Vietnam veterans or veterans
      receiving mental health services. This article compares characteristics and
      causes of death in Washington State veterans who did and did not use Department
      of Veterans Affairs (VA) healthcare services in the 5 years prior to death. This
      study included 62,080 veterans who died between 1998 and 2002, of whom 21% were
      users of VA healthcare services. The veterans who used VA healthcare services
      were younger, more often men, less educated, more often divorced, and more often
      smokers than the veterans who did not use VA healthcare services. Both female and
      male veterans who used VA healthcare services were more likely to die from drug-
      and/or alcohol-related causes. These findings suggest that the VA patient
      population is socially disadvantaged and more severely affected by substance-use
      disorders compared with veterans who do not use VA healthcare services.

PMID- 17436170
TI  - Demographic characteristics of veterans who received wheelchairs and scooters
      from Veterans Health Administration.
AB  - Little is known about the reasoning process clinicians use when prescribing
      wheeled mobility equipment (WME) or about the outcomes of this process, i.e., how
      many devices are prescribed, to whom, how often, and at what cost. This study
      characterized veterans who received WME from the Veterans Health Administration.
      We analyzed variance in wheelchair provision based on sex, race/ethnicity,
      diagnosis, and age. Three years of data from the National Prosthetics Patient
      Database and the National Patient Care Database were merged, yielding more than
      77,000 observations per fiscal year. Logistic regression analysis revealed
      associations between WME provision and age, sex, and race/ethnicity, when
      analysis was controlled for diagnosis and number of comorbidities. Hispanics
      (odds ratio [OR] = 1.864), African Americans (OR = 1.360), and American
      Indians/Asians (OR = 1.585) were more likely than Caucasians to receive standard
      wheelchairs. Hispanics (OR = 0.4), African Americans (OR = 0.7), and American
      Indians/Asians (OR = 0.4) were less likely than Caucasians to receive scooters.

PMID- 17436171
TI  - Reliability of near-infrared spectroscopy measures of cerebral oxygenation and
      blood volume during handgrip exercise in nondisabled and traumatic brain-injured
      subjects.
AB  - We compared the test-retest reliability of near-infrared spectroscopy (NIRS)
      measures of cerebral oxygenation and blood volume during a rhythmic handgrip
      exercise in 13 nondisabled subjects and 25 subjects with moderate to severe
      traumatic brain injury (TBI). Subjects with TBI (average Glasgow Coma Scale score
      = 4.2, average time since injury = 21 mo) had completed an acute brain injury
      rehabilitation program. After 2 min of rest, each subject performed 60 s of
      maximal rhythmic handgrip contractions with the right hand in two trials 24 to 48
      h apart. We used NIRS to measure cerebral oxygenation and blood volume responses
      from the left prefrontal lobe. Both groups' cerebral oxygenation and blood volume
      increased during handgrip contractions. The change in cerebral oxygenation was
      significantly lower in subjects with TBI compared with nondisabled subjects.
      Intraclass correlations between the two trials for cerebral oxygenation and blood
      volume were 0.83 and 0.80, respectively, in nondisabled subjects and 0.70 and
      0.64, respectively, in subjects with TBI. The findings indicate that NIRS is a
      reliable noninvasive technique for evaluating cerebral oxygenation and blood
      volume changes during motor function. NIRS can be useful in monitoring recovery
      of cerebral oxygenation during rehabilitation of patients with TBI.

PMID- 17436172
TI  - Kinematic and kinetic comparisons of transfemoral amputee gait using C-Leg and
      Mauch SNS prosthetic knees.
AB  - The C-Leg (Otto Bock, Duderstadt, Germany) is a microprocessor-controlled
      prosthetic knee that may enhance amputee gait. This intrasubject randomized study
      compared the gait biomechanics of transfemoral amputees wearing the C-Leg with
      those wearing a common noncomputerized prosthesis, the Mauch SNS (Ossur,
      Reykjavik, Iceland). After subjects had a 3-month acclimation period with each
      prosthetic knee, typical gait biomechanical data were collected in a gait
      laboratory. At a controlled walking speed (CWS), peak swing phase knee-flexion
      angle decreased for the C-Leg group compared with the Mauch SNS group (55.2
      degrees +/- 6.5 degrees vs 64.41 degrees +/- 5.8 degrees , respectively; p =
      0.005); the C-Leg group was similar to control subjects' peak swing knee-flexion
      angle (56.0 degrees +/- 3.4 degrees ). Stance knee-flexion moment increased for
      the C-Leg group compared with the Mauch SNS group (0.142 +/- 0.05 vs 0.067 +/-
      0.07 N"m, respectively; p = 0.01), but remained significantly reduced compared
      with control subjects (0.477 +/- 0.1 N"m). Prosthetic limb step length at CWS was
      less for the C-Leg group compared with the Mauch SNS group (0.66 +/- 0.04 vs 0.70
      +/- 0.06 m, respectively; p = 0.005), which resulted in increased symmetry
      between limbs for the C-Leg group. Subjects also walked faster with the C-Leg
      versus the Mauch SNS (1.30 +/- 0.1 vs 1.21 +/- 0.1 m/s, respectively; p = 0.004).
      The C-Leg prosthetic limb vertical ground reaction force decreased compared with
      the Mauch SNS (96.3 +/- 4.7 vs 100.3 +/- 7.5 % body weight, respectively; p =
      0.0092).

PMID- 17436173
TI  - Effect of system tilt and seat-to-backrest angles on load sustained by shoulder
      during wheelchair propulsion.
AB  - This study determined the effect of system tilt angle (STA) and seat-to-backrest
      angle (SBA) changes on the load sustained by the shoulder during manual
      wheelchair propulsion. Fourteen elderly participants (mean +/- standard deviation
      age 68.2 +/- 5.2 years) were recruited. Combinations of three STAs (0 degrees , 5
      degrees , and 10 degrees ) and three SBAs (95 degrees , 100 degrees , and 105
      degrees ) were randomly tested. The initial position of the wheel axle was held
      constant with respect to the participant's shoulder position in each condition
      (horizontal: 4 cm forward of shoulder, vertical: 110 degrees to 120 degrees elbow
      extension). The shoulder load was estimated by the joint moments. The analysis
      did not reveal any significant differences between shoulder joint moments
      (average and peak) for the various STA and SBA combinations. Changing the seat
      angle while keeping the wheel-axle position constant maintained the shoulder load
      at the same level. Thus, seat angle can be determined with the goals of user
      comfort and pressure modulation at the seat interface for alleviating pressure
      ulcers without increasing risk of overuse shoulder injuries.

PMID- 17436174
TI  - Magnetic resonance imaging technology in transtibial socket research: a pilot
      study.
AB  - Investigations into the shape and volume of transtibial prosthetic sockets are
      complicated because of the difficulty in establishing an accurate reference grid.
      Magnetic resonance imaging (MRI) presents a possible solution to this problem.
      However, the reliability of MRI in defining the residual-limb/cast interface
      depends on the scanned image not being distorted by the materials present. We
      investigated the potential of MRI technology to establish the desired reference
      grid. Distortion from the so-called "chemical shift" may influence the MRI when
      certain materials are used during the casting process. These materials include
      plaster of paris (POP) and silicone (in the form of an interface liner). POP is
      commonly used to capture the shape of the residual limb. However, if the casting
      technique requires the use of a silicone liner, the liner is placed over the
      residual limb first and then the POP is applied over the liner. Experimental
      results indicate that the materials used do not distort or interfere with the
      scanned image. The object segmentation process that extracts the bone and skin
      from an MRI scan and enables the establishment of the required reference grid was
      explored. Results show that extracting the bone structure and using it as the
      reference grid to quantify the differences in volume and shape of the soft
      tissues of the residual limb is feasible.

PMID- 17436175
TI  - Preamputation evaluation of limb perfusion with laser Doppler imaging and
      transcutaneous gases.
AB  - We studied 31 subjects with severe leg ischemia and 29 age-matched nonischemic
      control subjects to compare preamputation assessments of leg ischemia using laser
      Doppler imaging (LDI), transcutaneous partial pressure of oxygen (TcPO(2)), and
      transcutaneous partial pressure of carbon dioxide (TcPCO(2)). TcPO(2) and
      TcPCO(2) were evaluated with Novametrix Medical Systems, Inc, monitors
      (Wallingford, Connecticut) and perfusion (flux) of skin topically heated to 44
      degrees C, and adjacent nonheated areas were evaluated with a Moor Laser Doppler
      Imager (Moor Instruments, Ltd; Devon, England). LDI flux of heated areas, its
      ratio to nonheated areas, and TcPO(2) (not TcPCO(2)) were lower in ischemic
      subjects than in control subjects. LDI flux ratio performed better than TcPO(2)
      in identifying ischemia, with fewer false positive and false negative results.
      Moreover, LDI flux of heated skin detected a proximal to a distal gradient of
      perfusion in ischemic subjects, while TcPO(2) did not. LDI was superior to
      TcPO(2) in discriminating correctly between ischemic and nonischemic skin. The
      results suggest that an LDI ratio below 5 indicates nonviable skin.

PMID- 17436176
TI  - Locomotor training: experiencing the changing body.
AB  - This study examined the experiences of persons with incomplete spinal cord injury
      who participated in loco-motor training (LT). LT is an emerging rehabilitation
      intervention for enhancing the recovery of walking in persons with central
      nervous system disorders. Multiple interviews and field observations provided
      data from eight participants, including four veterans. Findings indicate that
      experiences of bodily changes were prevalent among participants. Themes included
      (1) experiencing impaired or absent proprioception, (2) struggling for bodily
      control, and (3) experiencing emergent bodily sensations. Themes 1 and 2
      reflected bodily disruption as a result of spinal cord injury and were
      challenging to participants as they attempted to reconnect the body and self
      through LT. Theme 3 reflected bodily sensations (burning, soreness) that were
      seen as positive signs of recovery and resulted in hope and motivation.
      Understanding how LT participants experience bodily changes may enable therapists
      to develop improved participant-centered intervention approaches.

PMID- 17436177
TI  - Risk factors associated with mortality in veteran population following
      transtibial or transfemoral amputation.
AB  - This study explored medical conditions associated with mortality among veterans
      following transfemoral amputation, transtibial amputation, or hip
      disarticulation. We applied logistic regression models to identify clinical
      factors associated with mortality postoperatively. The participants included
      patients with lower-limb amputations (n = 2,375) who were discharged from
      Veterans Health Administration hospitals between October 1, 2002, and September
      30, 2003. Most (98.9%) were male. We measured cumulative in-hospital, 3-month,
      and 1-year mortality. The results were 180 in-hospital deaths, 368 by 3 months,
      and 634 by the 1-year postsurgical amputation date. Those who had perioperative
      systemic sepsis (odds ratio = 4.28, 95% confidence interval = 2.87-6.39) had more
      than a fourfold increased likelihood of in-hospital mortality. Congestive heart
      failure, renal failure, and liver disease were significantly associated with
      mortality at all time periods. Metastatic cancer was associated only at 3 months
      and 1 year. We concluded that high medical complexity and mortality rates attest
      to the need for careful medical oversight during the postacute rehabilitation
      period.

PMID- 17436178
TI  - Cost of inpatient rehabilitation care in the Department of Veterans Affairs.
AB  - We investigated the determinants of inpatient rehabilitation costs in the
      Department of Veterans Affairs (VA) and examined the relationship between length
      of stay (LOS) and discharge costs using data from VA and community rehabilitation
      hospitals. We estimated regression models to identify patient characteristics
      associated with specialized inpatient rehabilitation costs. VA data included
      3,535 patients discharged from 63 facilities in fiscal year 2001. We compared VA
      costs to community rehabilitation hospitals using a sample from the Uniform Data
      System for Medical Rehabilitation of 190,112 patients discharged in 1999 from 697
      facilities. LOS was a strong predictor of cost for VA and non-VA hospitals.
      Functional status, measured by Functional Independence Measure (FIM) scores at
      admission, was statistically significant but added little explanatory value after
      controlling for LOS. Although FIM scores were associated with LOS, FIM scores
      accounted for little variance in cost after controlling for LOS. These results
      are most applicable to researchers conducting cost-effectiveness analyses.

PMID- 17436179
TI  - Exercise program implementation proves not feasible during acute care
      hospitalization.
AB  - Functional decline during hospitalization occurs in up to 65% of older adults.
      This study determined the feasibility of an inpatient followed by an in-home
      exercise program for patients with limited ambulatory ability on hospital
      admission. Patients aged >or=60 years who were admitted to the hospital with an
      acute medical illness associated with limited ambulatory ability were eligible
      for the study. Of 76 eligible patients, 10 were recruited, with only 1 patient
      completing the 24-week exercise program. Barriers to recruitment included illness
      severity, short hospital stays, and patient refusal. Hospital readmission during
      the in-home exercise program occurred for three of the seven exercise group
      participants. In the exercise group, four of the seven patients participated in
      at least 3 weeks of exercise posthospitalization. Qualitative interviews
      suggested most patients believed exercise to be beneficial, but this interest did
      not translate into adherence to this study protocol. Initiation of an inpatient
      exercise program was not feasible in the study population. The in-home program
      was more feasible but target criteria need refinement.

PMID- 17436180
TI  - [Flow-sensitive in-vivo 4D MR imaging at 3T for the analysis of aortic
      hemodynamics and derived vessel wall parameters].
AB  - Modern phase contrast MR imaging at 3 Tesla allows the depiction of 3D morphology
      as well as the acquisition of time-resolved blood flow velocities in 3
      directions. In combination with state-of-the-art visualization and data
      processing software, the qualitative and quantitative analysis of hemodynamic
      changes associated with vascular pathologies is possible. The 4D nature of the
      acquired data permits free orientation within the vascular system of interest and
      offers the opportunity to quantify blood flow and derived vessel wall parameters
      at any desired location within the data volume without being dependent on
      predefined 2D slices. The technique has the potential of overcoming the
      limitations of current diagnostic strategies and of implementing new diagnostic
      parameters. In light of the recent discussions regarding the influence of the
      wall shear stress and the oscillatory shear index on the genesis of
      arteriosclerosis and dilatative vascular processes, flow-sensitive 4D MRI may
      provide the missing diagnostic link. Instead of relying on experience-based
      parameters such as aneurysm size, new hemodynamic considerations can deepen our
      understanding of vascular pathologies. This overview reviews the underlying
      methodology at 3T, the literature on time-resolved 3D MR velocity mapping, and
      presents case examples. By presenting the pre- and postoperative assessment of
      hemodynamics in a thoracic aortic aneurysm and the detailed analysis of blood
      flow in a patient with coarctation we underline the potential of time-resolved 3D
      phase contrast MR at 3T for hemodynamic assessment of vascular pathologies,
      especially in the thoracic aorta.

PMID- 17436181
TI  - [Magnetic resonance imaging of single SPIO labeled mesenchymal stem cells at 3
      Tesla].
AB  - PURPOSE: To assess the detectability of single magnetically labeled mesenchymal
      stem cells (MSC) in-vitro on a clinical 3T MR scanner using a small animal volume
      coil. MATERIALS AND METHODS: GFP-transfected MSC were magnetically labeled with
      superparamagnetic iron oxide particles (SPIO) while applying different dosages of
      iron (56 vs. 560 microg Fe/ml). The cellular iron content was determined with
      atomic absorption spectrometry (AAS). Single labeled MSC were displayed in a
      culture flask using MR imaging and microscopy. Special cell phantoms were
      designed to examine the detection of labeled MSC with MR imaging in a spatial
      model. A T2*-weighted 3D gradient echo sequence with isotropic spatial resolution
      of 150 to 500 microm (3) was used for image acquisition. The detection of labeled
      MSC in the cell phantoms was quantitatively evaluated using an automated image
      analysis. Statistical analysis was performed with a significance level of p <
      0.05. RESULTS: The labeling of MSC yielded a mean cellular iron content of 1.5 +/
      0.17 pg Fe/cell (56 microg Fe/ml) and 8.3 +/- 1.85 pg Fe/cell (560 microg
      Fe/ml). Examination of the culture flasks showed single magnetically labeled MSC
      centered in much larger MR signal voids. The detection and quantification of
      single MSC in cell phantoms were feasible for spatial resolutions of 150 microm
      and 200 microm. Cells with a lower SPIO content (1.5 +/- 0.17 pg Fe/cell) were
      detected in 14.2 +/- 4.2 % (150 microm) and 7.7 +/- 3.8 % (200 microm). MSC with
      a higher cellular SPIO content (8.3 +/- 1.85 pg Fe/cell) revealed significantly
      higher occurrences at both spatial resolutions with 81.4 +/- 5.8 % (150 microm)
      and 59.9 +/- 12.4 % (200 microm), respectively. Regarding the spatial resolution
      (150 vs. 200 microm), significantly different detection rates were determined
      only for MSC with the higher SPIO content (8.3 +/- 1.85 pg Fe/cell). CONCLUSION:
      Detection of single magnetically labeled MSC is feasible on a clinical 3T MR
      scanner with a small animal volume coil at isotropic spatial resolutions of 150
      microm and 200 microm. The number of detected cells is influenced by the cellular
      iron content and the spatial resolution.

PMID- 17436182
TI  - [Experimental investigations for dose reduction by optimizing the radiation
      quality for digital mammography with an a-Se detector].
AB  - PURPOSE: Reduction of radiation exposure at an adequate image quality by
      optimizing the radiation quality for a new system of full-field digital
      mammography using a digital detector (a-Se). MATERIALS AND METHODS: The
      investigations were performed using a digital mammography system Novation
      (Siemens, Erlangen). The system was constructed with a bimetal anode (molybdenum
      and tungsten) and the possibility of changing the filter (molybdenum/rhodium).
      The test object was the Wisconsin Mammography Random Phantom Model 152 A
      (Radiation Measurements Inc.) of which images were acquired using the digital
      technique with the tungsten anode and rhodium filter at different tube voltages
      (26-35 kV) and tube loads (40-100 mAs) and compared to images in the
      molybdan/molybdan molybdenum/molybdenum technique. To quantify the image quality,
      we used the detection rate of the simulated lesions in the phantom. RESULTS:
      Increasing the tube voltage significantly decreases the average glandular dose
      when using AEC (Automatic Exposure Control), i. e., constant detector dose. At
      the same time, the image quality decreases significantly with respect to the
      detection rate (26 kV, 1 mGy, 95.1 %; 35 kV, 0.7 mGy, 82.7 %). As a good
      compromise between the necessary diagnostic image quality and the lowest dose
      exposition, 28 kV and 60 mAs were selected for imaging with the tungsten/rhodium
      anode/filter combination. A further change to the tube load did not make sense
      because a decrease of 10 % resulted in a significant decrease in the detection
      rate while only a 2 % increase in detection rate was achieved for a 65 % increase
      in radiation exposure. CONCLUSION: The results of this phantom study demonstrate
      that the routine use of the tungsten anode in combination with a rhodium filter
      for full-field digital mammography with an a-Se detector in contrast to a
      molybdan/molybdan molybdenum/molybdenum anode/filter combination results in a
      reduction of the average glandular dose of up to 30 % without loss of diagnostic
      image quality.

PMID- 17436183
TI  - [Comparing the clinical value of spot view mammography with reduced pixel size to
      monitor zooming by reporting microcalcifications in digital mammography].
AB  - PURPOSE: Evaluation of the diagnostic value of breast specimen imaging with a
      digital mammographic system using a detector system with changeable pixel size
      compared to standard mode imaging in different monitor display modes. MATERIALS
      AND METHODS: Using the digital mammographic system SenoScan (Fischer Imaging,
      Denver, USA), 50 diagnostic breast specimens with microcalcifications were
      visualized in both standard mode (pixel size 54 microm) and high resolution mode
      (pixel size 27 microm). The resulting radiographs were displayed 1:1 on a
      monitor. Standard mode images (pixel size 54 microm) were additionally displayed
      in a 2:1 mode. A total of 5 readers with different mammographic experience
      analyzed the type of the microcalcifications on the basis of the different
      display modes. The images were presented randomly. The findings were subsequently
      compared to the histology. RESULTS: The high resolution mode yielded slightly but
      not significantly better results than the standard mode on average for all 5
      readers. Compared to a sensitivity of 80 % and a specificity of 72 % (PPV = 74 %,
      NPV = 78 %) in the standard mode, the high resolution mode provided a sensitivity
      of 86 % and a specificity of 74 % (PPV = 77 %, NPV = 83 %). The standard mode
      images on a 2:1 monitor display yielded 84 % and 74 % (PPV = 76 %, NPV = 82 %).
      CONCLUSION: The high resolution mode did not significantly increase the
      sensitivity and specificity of the microcalcification reading. A similar
      improvement was achieved by the 2:1 display mode, i. e. digital monitor zooming.
      For the clinical situation this means that there is no diagnostic advantage from
      using a high resolution target view with this mammographic system.

PMID- 17436184
TI  - [MR thermometry for laser-induced thermotherapy at 1.5 Tesla].
AB  - PURPOSE: Evaluation of thermometry with fast MR sequences for laser-induced
      interstitial laser therapy (LITT) and verification of the thermometric results
      with a fiber-optic thermometer. METHOD AND MATERIALS: In vitro experiments were
      conducted using an agarose gel mixture and pig liver lobes. MR-guided LITT was
      performed using a laser power between 3 and 15 watts. Thermometry was performed
      using longitudinal relaxation time T1 and proton resonance frequency shift (PRF)
      methods under acquisition of amplitude and phase shift images. PRF was measured
      with a fast spoiled GRE sequence. Four different sequences were used for T1
      thermometry: gradient echo (GE), TrueFISP (TRUFI), Saturation Recovery Turbo
      FLASH (SRTF) and Inversion Recovery Turbo-FLASH (IRTF) sequences. The temperature
      was controlled using a fiber-optic Luxtron device and correlated with the MR
      temperature. The range of applied and monitored temperatures exceeded 80 degrees
      Celsius. RESULTS: The temperature dependence showed a good linear relationship up
      to 60 degrees Celsius. Calibration experiments for the T1 method delivered
      coefficients of determination from 0.977 to 0.997 for agarose and from 0.958 to
      0.995 for the pig liver samples. The IRTF sequence had the highest temperature
      sensitivity (agarose 0.99, liver 1.19). During LITT the TRUE-FISP sequence
      exhibited a strong nonlinear relationship. R (2) of this sequence was 0.809 in
      the agarose experiments. The average temperature errors when heated up to 80
      degrees Celsius were 3.86-11.38 degrees Celsius for Agarose gel and 5.7-12.16
      degrees Celsius for the liver tissue. SRTF and IRTF sequences exhibited the most
      linear relationship with temperature but were more dependent on tissue
      differences. CONCLUSION: The accuracy of the temperature measurement is
      sufficient for controlling the coagulation area of the LITT. PRF is the method of
      choice since it shows the best linear correlation with fiber-optic temperature.
      If only T1 sequences are concerned, the FLASH sequence is preferred. It is the
      most robust, though not the most accurate, T1 sequence.

PMID- 17436185
TI  - [MRI in the early stage of spinal cord injury: does it have clinical relevance?
      An experimental study].
AB  - PURPOSE: An experimental technique for producing a ventral spinal trauma which
      imitates a slipped intervertebral disc or a fractured vertebra was evaluated
      using magnetic resonance imaging and histology. The results were evaluated with
      respect to their clinical importance. MATERIALS AND METHODS: A total of 69 Wistar
      rats were used for this study. An inflatable angioplasty balloon device was
      placed dorsally or ventrally to the spinal cord in order to produce a spinal
      trauma. 30 rats were used to compare neurological pathologies between ventral and
      dorsal trauma. 30 animals underwent graded ventral spinal cord compression.
      Magnetic resonance imaging was performed and the results were compared to
      histology. RESULTS: Using this technique, the balloon device can be placed
      ventrally to the spinal cord. The compression time had a direct effect on changes
      on magnetic resonance images and edema in histology, but a longer compression
      time did not produce increased bleeding. The T2-weighted MRI scans showed
      hyperintense changes immediately after spinal compression. Therefore, they are
      the appropriate way for diagnosing acute spinal injuries. Although the T1
      weighted MRI scans did not change after spinal compression, they are important
      for diagnosing epidural hematomas. CONCLUSION: With this technique common ventral
      spinal trauma can be readily recreated. Magnetic resonance imaging allows early
      detection of edematous changes in experimental spinal cord injuries in the rat.

PMID- 17436186
TI  - [MRI of experimental focal cerebral ischemia in sheep].
AB  - PURPOSE: With respect to the specific characteristic of rete mirabile epidurale
      rostrale in sheep, the aim of this study was to investigate the use of time of
      flight (TOF) magnetic resonance angiography (MRA) to observe vascular anatomy and
      to validate MCA occlusion in a new model of experimental focal cerebral ischemia
      by permanent middle cerebral artery (MCA) occlusion in sheep (designed to study
      stroke therapy using autologous stem cells from umbilical cord blood).
      Furthermore, we wanted to assess the extent and natural time course of ischemic
      focal brain injury in sheep using functional and morphological magnetic resonance
      imaging (MRI). MATERIALS AND METHOD: 13 Merino sheep were examined. In 4 of the
      animals all, in 5 sheep 1 or 2 MCA branches were occluded and in 1 one case
      touched (sham operation). 4 controls did not undergo a surgical procedure. 23 MRI
      sessions were performed in 10 sheep. These sessions included T1, T2, T2*
      sequences, diffusion-weighted imaging (DWI) and TOF MRA before and 2-46 days
      after the onset of stroke using a 1.5 T clinical MR scanner. Corrosion casts of
      the cerebral arteries of 3 sheep were prepared and compared to MRA. RESULTS: The
      MRA visualized the vessel anatomy or occlusion distal to the rete mirabile.
      Anatomical variants concerning the variant origin of the MCA and inconstant
      arteria choroidea rostralis and communicans rostralis were revealed. Sheep with
      occluded left MCA showed space occupying lesions with a drop in ADC values.
      Depending on the number of preserved MCA branches (0; 1; 2), highly significant
      (p < 0.001) differences in lesion size (21 +/- 5.7; 13; 1.7 +/- 1.3 ml) could be
      found. No indication of ischemia but minimal contusion damage was observed in the
      sham operated animal. CONCLUSIONS: In our study focal cerebral ischemia was
      generated in sheep and examined using MRI for the first time. Depending on the
      occlusion type, the model produced a reproducible lesion size. TOF-MRA proved to
      be able to clearly depict the anatomy, variants and occlusion type of cerebral
      arteries in sheep in a manner comparable to that of corrosion casts despite the
      upstream rete mirabile. MRI with MRA is a useful tool for assessing the extent of
      brain injury and the type of MCA occlusion and is therefore suitable for non
      invasive monitoring of lesion development upon stroke.

PMID- 17436187
TI  - [Computerized analysis of brain perfusion parameter images].
AB  - PURPOSE: The development of a computerized method which allows a direct
      quantitative comparison of perfusion parameters. The display should allow a clear
      direct comparison of brain perfusion parameters in different vascular territories
      and over the course of time. The analysis is intended to be the basis for further
      evaluation of cerebral vasospasm after subarachnoid hemorrhage (SAH). The method
      should permit early diagnosis of cerebral vasospasm. MATERIALS AND METHODS: The
      Angiotux 2D-ECCET software was developed with a close cooperation between
      computer scientists and clinicians. Starting from parameter images of brain
      perfusion, the cortex was marked, segmented and assigned to definite vascular
      territories. The underlying values were averages for each segment and were
      displayed in a graph. If a follow-up was available, the mean values of the
      perfusion parameters were displayed in relation to time. The method was developed
      under consideration of CT perfusion values but is applicable for other methods of
      perfusion imaging. RESULTS: Computerized analysis of brain perfusion parameter
      images allows an immediate comparison of these parameters and follow-up of mean
      values in a clear and concise manner. Values are related to definite vascular
      territories. The tabular output facilitates further statistic evaluations. The
      computerized analysis is precisely reproducible, i. e., repetitions result in
      exactly the same output. CONCLUSION: Computerized analysis of brain perfusion
      parameters with Angiotux 2D-ECCET is objective and ensures reproducible results.
      It may become the basis and a requirement for the analysis of minimal changes in
      brain perfusion prior to irreversible damage from posthemorrhagic vasospasm.

PMID- 17436188
TI  - [Neuroradiologic findings in Mobius syndrome].

PMID- 17436189
TI  - [Early arterial enhancement of the liver: a pitfall in obstructions of the
      superior vena cava].

PMID- 17436190
TI  - [Guidelines for the diagnosis and therapy of COPD issued by Deutsche Atemwegsliga
      and Deutsche Gesellschaft fur Pneumologie und Beatmungsmedizin].

PMID- 17436191
TI  - Cardiorespiratory fitness of finnish adolescents.
AB  - We evaluated the accuracy of a submaximal cycle ergometer test to assess
      cardiorespiratory fitness in adolescents and provided population-based reference
      values. In a health study of the Northern Finland birth cohort born in 1985 -
      1986 (NFBC 1986), cardiorespiratory fitness of 5375 males and females aged 15 to
      16 years was measured by a submaximal cycle ergometer test by using a two-stage
      exercise protocol designed for this survey. A total of 4903 subjects performed
      two work stages. Maximal workload and peak oxygen consumption were calculated on
      the basis of heart rate responses by the WHO extrapolation method. An additional
      472 subjects were able to finish only one work stage. For them, peak oxygen
      uptake was calculated by the Astrand nomogram. To evaluate the accuracy of
      submaximal testing, a validation sample of 90 subjects carried out both a
      submaximal test and a maximal cycle ergometer test with direct measurement of
      peak oxygen uptake. The WHO method proved to estimate peak oxygen uptake with
      reasonable accuracy. The Astrand nomogram method overestimated peak oxygen uptake
      considerably, and therefore a new single-stage regression method was applied to
      calculate maximal workload and peak oxygen consumption. Reference values of
      cardiorespiratory fitness were provided for 2690 males and 2685 females aged 15
      to 16 years.

PMID- 17436192
TI  - Cardiorespiratory requirements of the 6-min walk test in older patients with left
      ventricular systolic dysfunction and no major structural heart disease.
AB  - The six-minute walk test (6-MWT) is widely used to assess functional status in
      patients with chronic heart failure (CHF). The aims of the present study were:
      (1) to compare metabolic gas exchange during the 6-MWT in older patients with
      left ventricular systolic dysfunction (LVSD) and in breathless patients with no
      major structural heart disease (MSHD); (2) to determine the exercise intensity of
      the 6-MWT relative to peak oxygen uptake; (3) to establish the accuracy and
      reproducibility of the Metamax 3B ergospirometer during an incremental workload.
      Twenty four older patients with LVSD (19 male; age 76 +/- 5 years; BMI 27 +/- 4),
      and 18 patients with no MSHD (12 male; age 75 +/- 8 years; BMI 27 +/- 4) attended
      on consecutive days at the same time. Patients completed a 6-MWT with metabolic
      gas exchange measurements using the Metamax 3B portable ergospirometer, and an
      incremental cycle ergometry test using both the Metamax 3B and Oxycon Pro
      metabolic cart. Patients returned and performed a second 6-MWT and an incremental
      treadmill test, metabolic gas exchange was measured with the Metamax 3B. In
      patients with LVSD, the 6-MWT was performed at a higher fraction of maximal
      exercise capacity (p = 0.02). The 6-MWT was performed below the anaerobic
      threshold in patients with LVSD (83 %) and in patients with no MSHD (61 %). The
      Metamax 3B showed satisfactory to high accuracy at 10 W and 20 W in patients with
      LVSD (r = 0.77 - 0.97, p < 0.05), and no MSHD (r = 0.76 - 0.94, p < 0.05).
      Metabolic gas exchange variables measured during the 6-MWT showed satisfactory to
      high day-to-day reproducibility in patients with LVSD (ICC = 0.75 - 0.98), but a
      higher variability was evident in participants with no MSHD (ICC = 0.62 - 0.97).
      The Metamax 3B portable ergospirometer is an accurate and reproducible device
      during submaximal, fixed rate exercise in older patients with LVSD and no MSHD.
      In elderly patients with LVSD and no MSHD, the 6-MWT should not be considered a
      maximal test of exercise capacity but rather a test of submaximal exercise
      performance. Our study demonstrates that the 6-MWT takes place at a higher
      proportion of peak oxygen uptake in patients with LVSD compared to those with no
      MSHD, and may be one reason why fatigue is a more prominent symptom in these
      patients.

PMID- 17436193
TI  - Exercise intensities during a ballet lesson in female adolescents with different
      technical ability.
AB  - To investigate the exercise intensity during a typical grade five ballet lesson,
      thirty-nine dancers (13 - 16 yrs) were divided into three different technical
      proficiency groups: low level (n = 13), intermediate level (n = 14), and high
      level (n = 12). A progressively incremented treadmill test was administered to
      determine VO(2max), individual ventilatory threshold (IVT), and the individual
      anaerobic threshold (IAT). Oxygen uptake (VO(2)), heart rate (HR) and blood
      lactate (La) were then evaluated during a grade five ballet lesson. Oxygen uptake
      at IVT, IAT and maximal oxygen uptake were greater (p < 0.05) in the high-level
      dancers indicating a higher level of fitness. HR and %VO(2max) obtained during
      the various exercises of the ballet lesson were similar among groups. During the
      ballet lesson, low technical level dancers had more V.O (2) and La values above
      (p < 0.05) the IAT than the other groups. Correlation analysis revealed that the
      number of exercises performed above IAT was positively related to anthropometric
      characteristics (BMI, %FM; r = 0.36, p < 0.05; r = 0.46, p < 0.01), negatively
      related to fitness parameters (VO(2IVT), VO(2IAT), VO(2max); r between - 0.43 and
      - 0.69; p < 0.001) and to technical level (r = - 0.70; p < 0.001). The subjects
      classified as having low technical abilities had lower fitness levels and
      performed more exercises above IAT than the more skilled dancers.

PMID- 17436194
TI  - Influence of testing sequence on a child's ability to achieve maximal anaerobic
      and aerobic power.
AB  - The aim of the study was to examine the order of testing sequence on a child's
      ability to achieve maximal anaerobic and aerobic power. Thirty-two children (20
      females, 12 males) between 7 - 11 years of age participated in this study. All
      subjects were tested on three separate occasions as follows: anaerobic power
      session - Wingate Anaerobic Test (WAnT) only; aerobic power session - maximal
      oxygen consumption (V.O (2max)) test only; and experimental session - WAnT
      followed by a V.O (2max) test (WAnT/V.O (2max)) or a V.O (2max) test followed by
      a WAnT (V.O (2max)/WAnT), each with 20 minutes of rest between the assessments.
      No significant differences were observed between the baseline WAnT or V.O (2max)
      between the two groups. No significant differences were observed for WAnT power
      values in either group regardless of testing sequence. Children in the WAnT/V.O
      (2max) group had significantly lower experimental V.O (2max) (38.6 +/- 7.6 vs.
      40.6 +/- 7.4 mL . kg (-1) . min (-1); p < 0.05), RER (1.10 +/- 0.08 vs. 1.13 +/-
      0.07; p < 0.05), and exercise time (472 +/- 87 vs. 511 +/- 79 s; p < 0.01) values
      when compared to the baseline V.O (2max) test. The results of this study indicate
      that when assessing a child's anaerobic and aerobic power during the same testing
      session, the testing sequence is of importance. However, it appears that a V.O
      (2max) test can be performed 20 minutes prior to the WAnT without affecting
      anaerobic power in children.

PMID- 17436195
TI  - Asthma in Tunisian elite athletes.
AB  - Several studies in the past few decades have shown that very intense and repeated
      exercise, particularly when performed over many years, could cause respiratory
      health problems. The prevalence of exercise-induced asthma has increased in the
      athletic population, particularly in elite athletes and has not been published in
      North African athletes. The aim of this study was to determine the prevalence of
      exercise-induced asthma and/or exercise-induced bronchoconstriction in Tunisian
      elite athletes. Each participant responded to a questionnaire about respiratory
      symptoms and medical history and underwent a resting spirometry testing before
      exercise. Exercise-induced bronchoconstriction was defined as a decrease of at
      least 15% in pre-exercise forced expiratory volume in one second at any time
      point after exercise. Post-exercise spirometry revealed the presence of exercise
      induced bronchoconstriction in 14 out of 107 (13%) elite athletes, while only
      1.8% of the subjects reported having previously diagnosed asthma. The prevalence
      of exercise-induced bronchoconstriction was 19% (8/42) among those athletes
      training outdoors and 10% (6/65) among those training indoors. In conclusion, our
      findings indicate that a significant number of Tunisian athletes had exercise
      induced bronchoconstriction while not diagnosed before.

PMID- 17436196
TI  - The effect of basketball training on the players' erythrocyte membrane
      acetylcholinesterase, (Na+,K+)-ATPase and Mg2+-ATPase activities.
AB  - The aim of this study was to investigate whether the activities of erythrocyte
      membrane acetylcholinesterase (AChE), (Na (+),K (+))-ATPase and Mg (2+)-ATPase
      are modulated by a basketball training. Blood was obtained from 10 basketball
      players pre- and postexercise. Total antioxidant status (TAS), lactate and
      pyruvate concentrations were determined with kits, while the enzyme activities
      were determined spectrophotometrically. Post-training blood lactate and pyruvate
      concentrations as well as AChE (2.90 +/- 0.05 vs. 3.98 +/- 0.09 Delta OD/min . mg
      protein, p < 0.01) and Na (+),K (+)-ATPase (0.58 +/- 0.04 vs. 1.27 +/- 0.12
      micromol Pi/h . mg protein, p < 0.001) activities were remarkably increased,
      whereas TAS was significantly decreased. Mg (2+)-ATPase activity remained
      unaltered at the end of the training. In conclusion, the stimulation of AChE and
      Na (+),K (+)-ATPase by the training may be due to the rise of blood catecholamine
      oxidation contributing to TAS decrease and/or the increase of serotonin levels.
      This stress condition may modulate cholinergic and
      catecholaminergic/serotoninergic functions in players.

PMID- 17436197
TI  - LDL particle size in habitual exercisers, lean sedentary men and abdominally
      obese sedentary men.
AB  - Habitual exercisers enjoy considerable protection from coronary heart disease
      (CHD). Often, however, only modest differences in traditional CHD risk factors
      are apparent between habitual exercisers and their sedentary counterparts. For
      this reason, there is increasing interest in novel predictors of CHD, such as a
      preponderance of small, dense low-density lipoprotein (LDL) particles.
      Polyacrylamide gel electrophoresis was used to separate lipoprotein subfractions
      in 32 lean exercisers, 36 lean sedentary men and 21 obese sedentary men aged 30 -
      45 years. Well-validated equations were used to determine LDL concentration and
      peak particle diameter. Waist girth was used to identify lean (< 100 cm) and
      obese (>or= 100 cm) individuals. LDL concentration was lower in lean exercisers
      than in lean sedentary men (2.64 +/- 0.44 vs. 3.76 +/- 0.79 mmol . l (-1), p <
      0.001), suggesting that habitual exercise influences this risk factor. In
      contrast, there were no significant differences in LDL peak particle diameter
      between lean exercisers, lean sedentary men and obese sedentary men (27.92 +/-
      0.67, 28.09 +/- 0.62 and 27.77 +/- 0.77 nm, respectively). In multiple linear
      regression analysis, triglyceride concentration was the only significant
      predictor of LDL PPD. These data suggest that habitual exercise influences LDL
      concentration but does not influence LDL particle size in men aged 30 - 45 years.

PMID- 17436198
TI  - Changes of bone turnover markers after marathon running over 245 km.
AB  - We evaluated bone turn over markers, cortisol and parathyroid hormone (PTH)
      levels in male athletes after 245 km of marathon running. Sixteen athletes were
      studied five days before, immediately after, and 1, 3, and 5 days after the run.
      We used T-test and Pearson correlation for statistical analysis. Osteocalcin
      levels were significantly decreased from 4.6 microg/lit to 3.8 microg/lit (p <
      0.05). Activity of b-ALP was significantly decreased from 66 U/lit to 61.5 U/lit
      (p < 0.05). PICP levels were also significantly decreased from 168 microg/lit to
      153 microg/lit (p < 0.05). Hydroxyproline levels decreased after the run from 70
      mmol/min to 65 mmol/min (p < 0.05). ICTP levels increased after the run but
      without being statistically significant, from 6.62 microg/lit to 7.0 microg/lit.
      Urine calcium decreased significantly by 68 %, immediately after the run.
      Cortisol increased from 212 ng/ml to 455 ng/ml, and PTH levels increased from 12
      pg/lit to 16 pg/lit immediately after the race (p < 0.05). Cortisol levels were
      significantly negatively correlated with osteocalcin (r = - 0.61, p < 0.05) and b
      ALP (r = - 0.98, p < 0.05). PTH levels were significantly negatively correlated
      only with serum osteocalcin (r = - 0.8, p < 0.05). These findings suggest a
      transient suppression in osteoblast function during the marathon run probably due
      to cortisol and PTH levels elevation.

PMID- 17436199
TI  - Effect of aspirin and ibuprofen on GI permeability during exercise.
AB  - This study was conducted to determine the effects of aspirin or ibuprofen on
      gastrointestinal permeability when combined with exercise. Eight runners
      completed three 60 min treadmill runs at 70 % VO(2max). For 24 hours prior to
      each run, subjects ingested aspirin (2 x 325 mg), ibuprofen (2 x 200 mg), or
      placebo capsules every 6 hours. Immediately before each run, a solution
      containing 5 g sucrose, 5 g lactulose, and 2 g rhamnose was ingested. Urine
      produced during each run, and for 4 h afterwards was collected. Urinary excretion
      of sucrose is an indicator of gastroduodenal permeability. The excretion ratio of
      lactulose-to-rhamnose assesses small intestinal permeability. Sucrose excretion
      (%) was greater (p < 0.017) for aspirin (0.37 [0.2 - 0.97]) compared to placebo
      (0.09 [0.05 - 0.30]) or ibuprofen (0.22 [0.1 - 0.39]) and sucrose excretion for
      ibuprofen was greater than placebo. The lactulose-to-rhamnose ratio was greater
      for aspirin (0.09 [0.08 - 0.30]) than placebo (0.065 [0.04 - 0.08]) however
      ibuprofen (0.08 [0.06 - 0.19]) was not different from aspirin or placebo. These
      results indicate that with prolonged running, gastroduodenal permeability is
      increased if aspirin or ibuprofen is used prior to such exercise. Furthermore,
      aspirin promotes greater gastroduodenal permeability and also increases small
      intestinal permeability.

PMID- 17436201
TI  - Freewheel exercise training modifies pro- and anti-apoptotic protein expression
      in mouse splenic lymphocytes.
AB  - The purpose of this study was to examine the effect of voluntary training in mice
      on the expression of apoptotic proteins in splenic lymphocytes following acute
      exercise. Thirty-three mice were randomized to four treatments: 1) control group
      (no training and no acute exercise), 2) training, no acute exercise, 3) no
      training, acute exercise and 4) training, acute exercise. Mice were sacrificed
      immediately after acute exercise. Western immunoblotting was used to detect
      apoptosis in splenic lymphocytes for concentrations of anti- (Bcl-2) and pro
      apoptotic (caspase 3) proteins. Plasma corticosterone was used as an index of
      exercise stress. Trained mice not given acute exercise challenge had elevated Bcl
      2 (p < 0.05) and lower caspase 3 (p < 0.05) levels relative to control mice.
      Following the acute exercise challenge, however, trained and untrained mice did
      not differ in the concentrations of these proteins in splenocytes. Thus,
      freewheel exercise training in mice reduces splenic lymphocyte apoptosis when
      tissue samples are obtained at rest but not after acute exercise.

PMID- 17436200
TI  - Imbalanced nutrition of top-level swimmers.
AB  - The aim of the present study was to monitor the nutritional status of 9 Greek
      national top-level swimmers during a competitive season of eight months. The
      swimmers were assessed through recording of food and supplement intake, blood
      sampling, and anthropometry at four landmarks: in the beginning of the season
      (baseline), after completing a phase of intensive and voluminous training (at 10
      weeks), at a minor taper (19 weeks), and during the major taper (32 weeks).
      Energy and macronutrient intake did not change significantly over time, and only
      a few significant changes were found in micronutrient intakes. Low carbohydrate
      and high fat intakes (e.g., 36 and 42 % of total energy, respectively, in males),
      inadequate intake of some micronutrients, and improper use of supplements
      indicated suboptimal dietary habits. Blood hemoglobin fluctuated significantly
      during the season. No significant changes in parameters indicative of the iron
      stores (transferrin saturation and ferritin) were found, although iron intake
      increased by supplementation with the onset of training. Serum markers of
      training stress were not significantly altered. In conclusion, Greek top-level
      swimmers should be guided toward a balanced diet and a rational use of
      supplements. Monitoring of dietary intakes during a competitive season is highly
      recommended.

PMID- 17436202
TI  - Echinacea purpurea and mucosal immunity.
AB  - This investigation examined the effects of Echinacea purpurea on mucosal immunity
      and the incidence and duration of upper respiratory tract infection (URTI). 32
      subjects completed an exercise protocol known to affect mucosal immunity. Saliva
      was collected prior to and five minutes after completion of exercise testing.
      Subjects then took either a placebo (C) or Echinacea supplement (E) for 4 weeks
      and the testing procedure was repeated. Each time, s-IgA concentrations and
      saliva flow rate were measured and the secretion rate of s-IgA was calculated. In
      addition, standard logs indicating symptoms of URTI were completed throughout the
      study. Both groups demonstrated significant exercise induced reductions in s-IgA
      (C - 69 %; E - 43 %) and the secretion rate of s-IgA (C - 79 %; E - 53 %) at the
      beginning of the study (p < 0.05). Following the 4-week intervention, only the
      control group experienced the post intervention decrease in s-IgA (C - 45 %; E +
      7 %) and the secretion rate of s-IgA (C - 45 %; E - 7 %). Further, while there
      was no significant difference in the number of URTI between groups, the reported
      duration was significantly different (C 8.6 days vs. E 3.4 days). The results
      suggest that Echinacea may attenuate the mucosal immune suppression known to
      occur with intense exercise and reduce the duration of URTI that subjects incur.

PMID- 17436203
TI  - Modulation of dendritic cells by endurance training.
AB  - A periodized endurance training is able to adapt physical and psychological needs
      and increase exercise performance. Dendritic cells (DCs) play a key role in
      regulation of the immune response. In the present study, we trained Sprague
      Dawley (SD) rats for five weeks using a progressive endurance protocol with the
      aim of measuring the effect on myeloid DC differentiation and maturation. Rats
      were divided into a non-exercise group (NEG) and an exercise group (EG). Bone
      marrow cells were isolated from these rats after training and cultured in the
      presence of granulocyte/monocyte-colony stimulatory factor (GM-CSF) and
      interleukin (IL)-4, and the resultant immature DCs were triggered with
      lipopolysaccharide to mature. DCs were collected and the main characteristics of
      DCs were assessed. The recovery rate and the expression of major
      histocompatibility complex (MHC) class II molecules for DC collected from EG was
      markedly greater than NEG. The function of DCs from EG to trigger a mixed
      leukocyte reaction and IL-12 production was higher than NEG. There was no liver
      and renal toxicity observed in all rats. Changes in food/water consumption and
      body weight increase between the groups were normal for the conditions. This
      study demonstrated that periodized endurance training is able to modulate DC
      development and shift them towards a more mature state.

PMID- 17436204
TI  - Adherence to a home-based exercise program and incidence of cardiovascular
      disease in type 2 diabetes patients.
AB  - The aim of this study was to examine the association between adherence to a home
      based exercise program and the incidence of cardiovascular disease (CVD) in
      patients with type 2 diabetes. We investigated 102 patients with type 2 diabetes
      aged 35 to 75 years, and followed them prospectively for 17.2 months. Before
      enrollment, all patients received a traditional exercise prescription. The
      exercise program consisted of a daily walking exercise at home for 20 - 30
      minutes. Self-reported adherence to the exercise program and the incidence of CVD
      were confirmed by information obtained from telephone interviews. There were 38
      dropouts among the patients in the exercise program. Dropouts were significantly
      younger than completers. The rate of obesity was significantly higher among the
      dropouts than among the completers. No differences were observed between the two
      groups for gender, history of CVD and other clinical characteristics. During the
      follow-up, we documented 8 new cases of CVD. The incidence of CVD during the
      follow-up was 1.56 percent among the program completers and 18.4 percent among
      the dropouts. Adherence to the home-based exercise was inversely related to the
      incidence of CVD (p < 0.01). These associations persisted after adjustment for
      age and other covariates. In conclusion, adherence to an exercise program is
      associated with a reduced incidence of CVD among patients with type 2 diabetes.

PMID- 17436205
TI  - Mechanical efficiency and wheelchair performance during and after spinal cord
      injury rehabilitation.
AB  - The purpose of the present study was to investigate whether mechanical efficiency
      (ME) relates to wheelchair propulsion capacity and wheelchair performance tasks
      during and after rehabilitation of people with a spinal cord injury (SCI). Eighty
      participants with a SCI were tested during rehabilitation (3 x) and 1 year after
      discharge. Two 3-minute submaximal exercise blocks, a maximal wheelchair exercise
      test, and four wheelchair performance tasks were performed. ME, peak power output
      (PO (peak)), the sum of the performance times of a 15-m sprint and figure-of
      eight, and the heart rate reserve (%HRR) during 10 s of wheelchair propulsion on
      a 3 % and 6 % slope were calculated. The relationship between ME and PO (peak),
      %HRR and performance time was tested with a multilevel regression analysis. ME
      showed a significant relationship with PO (peak) (p </= 0.002). A 1 % higher ME
      related to a 1.6 - 2.2 W higher PO (peak). ME of exercise block 2 was related to
      the sum of the performance times of a 15-m sprint and figure-of-eight; the tests
      were performed faster by participants with a higher ME. No relationship was found
      between ME and %HRR during wheelchair propulsion on a slope. ME showed a
      significant effect on wheelchair propulsion capacity and wheelchair performance
      time during and 1 yr after SCI rehabilitation although the isolated effect of ME
      is small.

PMID- 17436206
TI  - Elite athletes: is survival shortened in boxers?
AB  - Moderate exercise and intense physical training are associated with increased
      life expectancy (LE). Boxing is characterized by intentional and repetitive head
      blows, sometimes causing brain injury, possibly reducing LE. We examined a sample
      of male athletes born between 1860 and 1930 selected from the international "hall
      of fame" inductees in baseball (n = 154), ice hockey (n = 130), tennis (n = 83),
      football (n = 81), boxing (n = 81), track and field (n = 59), basketball (n =
      58), swimming (n = 37) and wrestling (n = 32). In boxing, we analyzed the number
      of disputed bouts/rounds and career records. Sports were also analyzed according
      to physiological demand and occurrence and kind of contact (intentional,
      unintentional). The Kaplan-Meier product limit method was used to compare
      survival curves (significance: p <or= 0.05). Median LE of the samples was 76.0
      yrs and no differences were observed in different sports, although it was lower
      in boxers (73.0 yrs) and higher in tennis players (79.0 yrs). Sports of different
      physiological demand were similar in respect to LE. No differences in LE were
      found related to occurrence and kind of impact. Similar LE was found in boxers of
      different weight or career records. In conclusion, this study indicates that LE
      in top-level athletes is unaffected by the type of discipline, and not related to
      physiological demand and intentional contact.

PMID- 17436207
TI  - [HKZ: Harmonization of Quality Judgment in the Care Sector].

PMID- 17436208
TI  - [Risk assessment and treatment evaluation by means of two forensic observation
      instruments].
AB  - BACKGROUND: Under the Dutch TBS system (compulsory detention by government
      order), risk assessment and treatment evaluation are closely linked procedures.
      AIM: To test the psychometric properties of two observation instruments developed
      specifically for evaluating the treatment of persons compulsory detained (tbs).
      METHOD: Two observation instruments for the use of social therapists and/or group
      leaders were tested on the basis of measurements obtained at the 'Meijers
      Instituut'(n=556) and at the 'De Kijvelanden'(n=100). The two instruments, one
      called the STM list (list for social therapists) and the other called the 'coping
      list', are questionnaires. The lists are designed to measure characteristics such
      as social skills, cooperation, daily living skills and coping skills in forensic
      psychiatric patients. These characteristics are believed to be important
      predictors of risk of future criminal behaviour. RESULTS: The internal
      consistency for the two questionnaires was found to be good. The results obtained
      at 'De Kijvelanden' showed that the STM questionnaire had adequate test-retest
      reliability. The STM total scores and subscale scores were found to be
      significantly associated with criminal recidivism. Anti-social behaviour on the
      ward, daily living skills and social skills, and to a lesser extent cooperation
      and negative coping styles, were found to be associated with future relapse into
      criminal behaviour. CONCLUSION: The questionnaires appear to be suitable for
      repeated assessing the effects of treatment on behaviour in forensic psychiatric
      settings and could possibly serve as useful supplements to other risk assessment
      methods that are currently available.

PMID- 17436209
TI  - [The relevance of sexuality in the treatment of borderline personality disorder].
AB  - BACKGROUND: Although many articles about borderline personality disorder have
      been published over the last 25 years, sexuality has not received much attention.
      Sexual functioning may however be relevant for the treatment of this disorder.
      AIM: To find out from research reports, the literature and clinical practice
      whether they contain evidence of varying degrees of problematical sexuality in
      borderline patients, and if so, to make an inventory of the evidence. METHOD: A
      literature search was conducted via PubMed and Psycinfo using the search terms
      'borderline personality disorder', 'sexuality' and 'research'. In addition, the
      literature was searched manually. RESULTS: Only six empirical studies about the
      sexual functioning of patients with borderline personality disorder were found.
      The research findings provided information about patients' problems with regard
      to intimate and sexual relations. These problems related to heightened sexual
      impulsivity, reduced satisfaction, increased sexual boredom, greater
      preoccupation with sex, avoidance of sex and a range of other sexual complaints.
      In addition, there is evidence that homosexuality and vulnerability regarding
      gender identity occur more frequently in these patients. CONCLUSION: Helping to
      integrate love and sexuality with a suitable partner seems to be an important
      developmental assignment for persons assisting borderline patients.

PMID- 17436210
TI  - [Sensitive to change: neuroendocrinologic aspects of depression in women].
AB  - BACKGROUND: Depression is more prevalent among women than among men. There are
      several possible explanations for this. There are indications that the aetiology
      of this difference in prevalence has to do with fluctuations in the oestrogen
      level, which are a feature of the female reproductive system. The influence of
      oestrogens on the hypothalamic-pituitary-adrenal axis may play an important role.
      AIM: To cast light on the deregulating influence of oestrogen on the hypothalamic
      pituitary-adrenal axis. This deregulation could lead to depression in a subgroup
      of women with a neuroendocrine stress response that is sensitive to hormonal
      fluctuations. METHOD: PubMed was used to review the literature on the basis of
      the key words 'depression', 'estrogen', 'gender', 'gonadal hormones', 'hpa axis',
      'stress' and 'women'. RESULTS: Deregulation of the hypothalamic-pituitary-adrenal
      axis plays a role in the aetiology of major depression. On the one hand,
      oestrogens stimulate the activity of this system. On the other hand, a lowering
      of the endogenous oestrogen level seems to be accompanied by reduced activity of
      the hypothalamic-pituitary-adrenal axis. CONCLUSION: Changing oestrogen levels
      characterise the female reproductive system. It is these changing levels--not the
      absolute oestrogen level--which have the potential to deregulate the hypothalamic
      pituitary-adrenal axis.

PMID- 17436211
TI  - [Oculotoxic and dermatotoxic side effects of phenothiazines].
AB  - Phenothiazines can give rise to serious and sometimes irreversible dermatological
      and oculotoxic side effects. These effects can take the form of photosensitivity,
      grey-purple discoloration and hyperpigmentation of the skin and hyperpigmentation
      of the conjunctiva, cornea, lens, retina, choroidea and macula. Involvement of
      the retina or macula can lead to impaired vision, blurred vision, disturbed
      colour perception and night blindness. We describe the mechanisms that are
      currently believed to underlie these side-effects. We advise annual ophthalmic
      monitoring of patients receiving long-term treatment with phenothiazianes.

PMID- 17436212
TI  - [Autism and catatonia: successful treatment using lorazepam. A case study].
AB  - A 24-year-old man who was mentally retarded and had an autistic disorder,
      developed mutism and motor symptoms. He was diagnosed with catatonia and was
      treated successfully with lorazepam. Additionally, we review the literature about
      the diagnosis and treatment of catatonia in patients with autism; in such cases
      accurate diagnosis is vital but is complicated by overlapping symptoms.

PMID- 17436213
TI  - [Quetiapine in the treatment of the Gilles de la Tourette syndrome. A case
      study].
AB  - In this article we describe the clinical response of an 8-year-old boy with the
      Gilles de la Tourette syndrome (GTS) when treated with quetiapine. Upon admission
      for observation he received a trial course of quetiapine, to which he responded
      favourably. We searched the Medline and Psycinfo databases for information about
      the recommended dose of quetiapine for children with GTS. From the 12 case
      studies and one open-label trial that we found, we conclude that the maximum dose
      of quetiapine for children with GTS is 200 mg. Data concerning the safety of
      quetiapine when administered to children are limited and contradictory.

PMID- 17436216
TI  - Resistance to antiretroviral drugs: a threat to the prevention and treatment of
      pediatric HIV infection.

PMID- 17436217
TI  - The time to treat the children is now.

PMID- 17436218
TI  - Pharmacogenomics, toxicogenomics, and DNA polymerase gamma.

PMID- 17436219
TI  - Early archiving and predominance of nonnucleoside reverse transcriptase inhibitor
      resistant HIV-1 among recently infected infants born in the United States.
AB  - BACKGROUND: The extent to which drug-resistant human immunodeficiency virus type
      1 (HIV-1) acquired through mother-to-child transmission (MTCT) or failed
      chemoprophylaxis populates viral reservoirs and limits responses to
      antiretroviral treatment in infants is unknown. METHODS: We evaluated the
      presence, type, and persistence of drug-resistant HIV-1 in pretreatment plasma
      and resting CD4(+) T cells from US infants enrolled in a multicenter, open-label,
      phase 1/2 treatment trial of lopinavir/ritonavir (Pediatric AIDS Clinical Trials
      Group Protocol 1030) in young infants. RESULTS: Twenty-two consecutively enrolled
      infants initiating highly active antiretroviral therapy at a median age of 9.7
      weeks and treated for up to 96 weeks were studied. Drug-resistant HIV-1 was
      present in 5 (23.8%) of 21 infants analyzed; 4 (80.0%) had nonnucleoside reverse
      transcriptase inhibitor (NNRTI)-resistant HIV-1, only 1 of whom had a history of
      receiving nevirapine chemoprophylaxis. All 4 infants had NNRTI-resistant variants
      other than the K103N mutation. The fifth infant had the M184V mutation. Drug
      resistant virus was archived in the resting CD4(+) T cell latent reservoir in all
      5 infants. CONCLUSIONS: The high rate, types, and early archiving of drug
      resistant HIV-1 suggests that resistance testing be considered for infants,
      especially when an NNRTI-based regimen is planned. Furthermore, drug-resistance
      outcomes in infants should be an important secondary end point in MTCT trials.

PMID- 17436220
TI  - Antiretroviral therapy for HIV-1-infected children in Haiti.
AB  - BACKGROUND: Data are limited about the effectiveness of pediatric antiretroviral
      therapy (ART) in low-income countries. METHODS: We report the outcomes of
      consecutively treating 236 human immunodeficiency virus type 1 (HIV-1)-infected
      treatment-naive children with triple ART in Port-au-Prince, Haiti, between 1 May
      2003 and 30 April 2006. RESULTS: Kaplan-Meier survival analysis at follow-up
      demonstrated that 191 children (81%) remained in care, 21 (9%) were dead, and 24
      (10%) were lost to follow-up. Independent baseline predictors of mortality were
      age <18 months, CD4(+) T cell percentage < or =5%, and weight-for-age Z score
      (WAZ) less than -3. Twelve months into ART, 56% of tested subjects had
      undetectable HIV-1 RNA loads. Median CD4(+) T cell percentages at 12 months
      increased by 15%, 11%, and 5% in children with baseline percentages of < or =5%,
      6%-24%, and > or =25%, respectively (P<.01). The median WAZ at 12 months
      increased by 1.0, 0.6, and 0.2 in children with baseline WAZ less than -2, -2 to 
      1.1, and -1 or more, respectively (P<.01). CONCLUSION: With continuous donor
      support, trained providers, and the availability of pediatric antiretroviral drug
      formulations, it proved feasible to deliver pediatric ART in Haiti. The
      effectiveness of this program should encourage efforts to make ART available for
      HIV-infected children in poor countries.

PMID- 17436221
TI  - Novel mutation of human DNA polymerase gamma associated with mitochondrial
      toxicity induced by anti-HIV treatment.
AB  - Mitochondrial toxicity is a major adverse effect of the nucleoside reverse
      transcriptase inhibitors (NRTIs) used for treatment of human immunodeficiency
      virus type 1 (HIV-1) infection and can result in life-threatening lactic
      acidosis. The toxicity is due to inhibition of polymerase gamma (Pol gamma),
      which is required for replication of mitochondrial DNA (mtDNA). Genetic factors
      could be involved in this process, given that not all NRTI-treated patients
      experience the toxicity. In 1 patient with lactic acidosis, a novel homozygous
      Pol gamma mutation (arginine to cysteine at codon 964 [R964C]) was identified at
      a site close to polymerase motif B, which is highly conserved among family A
      polymerases. Recombinant R964C Pol gamma showed only 14% activity, compared with
      that of wild-type Pol gamma. Culture with stavudine significantly reduced mtDNA
      levels in patient-derived lymphoblastoid cell lines (LCLs) harboring R964C Pol
      gamma, compared with those in LCLs harboring wild-type Pol gamma. The novel Pol
      gamma mutation could be associated with the severe lactic acidosis induced by
      long-term NRTI use.

PMID- 17436222
TI  - Interruption of antiretroviral treatment in HIV-infected patients with preserved
      immune function is associated with a low rate of clinical progression: a
      prospective study by AIDS Clinical Trials Group 5170.
AB  - BACKGROUND: We sought to determine the safety of treatment interruption (TI) and
      to identify parameters that would define patients with human immunodeficiency
      virus (HIV) for whom TI is safer. METHODS: AIDS Clinical Trials Group 5170 was a
      multicenter, 96-week-long, prospective study of HIV-infected patients receiving
      antiretroviral therapy (ART) who had CD4(+) cell counts >350 cells/mm(3) and who
      underwent TI. RESULTS: A total of 167 patients were enrolled. The median nadir in
      CD4(+) cell count was 436 cells/mm(3). The initial decrease (i.e., during the
      first 8 weeks) in CD4(+) cell count after ART interruption was 20
      cells/mm(3)/week; the subsequent decrease was 2.0 cells/mm(3)/week until week 96.
      Both the CD4(+) cell count before enrollment and the increase in CD4(+) cell
      count during ART predicted early decrease; later decrease was predicted by the
      level of interleukin-7 at enrollment. A Centers for Disease Control and
      Prevention (CDC) diagnosis of a category B or C event was made for 2 and 2
      patients, respectively (all had CD4(+) cell counts >350 cells/mm(3)). At week 96,
      17 patients had CD4(+) cell counts < or =250 cells/mm(3), and 46 patients had
      resumed ART; 5 patients died (unrelated to HIV or acquired immunodeficiency
      syndrome). In a multivariate analysis, a higher nadir in CD4(+) cell count (>400
      cells/mm(3)), a lower HIV load (<50 copies/mL) at the time of TI, and an HIV load
      < or =22,000 copies/mL before ART predicted a longer time to the primary end
      point (CDC category B or C event, death, CD4(+) cell count < or =250 cells/mm(3),
      or resumption of ART). CONCLUSION: Disease progression after TI was low in this
      cohort. A higher nadir in CD4(+) cell count, a lower HIV load before ART, and an
      HIV load < or =50 copies/mL at the time of TI predicted a longer time to the
      primary end point.

PMID- 17436223
TI  - Isolated hepatitis B core antibody is associated with HIV and ongoing but not
      resolved hepatitis C virus infection in a cohort of US women.
AB  - To characterize predictors of isolated hepatitis B core antibody (anti-HBc) among
      human immunodeficiency virus (HIV)-infected and HIV-uninfected women, we compared
      702 women with anti-HBc and hepatitis B surface antibody (anti-HBs) with 490
      women with isolated anti-HBc (1.8% of whom had detectable hepatitis B virus [HBV]
      DNA). Factors independently associated with isolated anti-HBc without viremia
      were detectable hepatitis C virus (HCV) RNA, HIV positivity, history of injection
      drug use, >10 lifetime sex partners, and HIV RNA level >100,000 copies/mL. Anti
      HBs levels were lower among anti-HCV-positive women. Isolated anti-HBc was rarely
      explained by occult HBV in this cohort but may be explained by the influence of
      viral coinfections on anti-HBs level or durability.

PMID- 17436224
TI  - Experimental infection with Haemophilus ducreyi in persons who are infected with
      HIV does not cause local or augment systemic viral replication.
AB  - We infected 11 HIV-seropositive volunteers whose CD4(+) cell counts were >350
      cells/ microL (7 of whom were receiving antiretrovirals) with Haemophilus
      ducreyi. The papule and pustule formation rates were similar to those observed in
      HIV-seronegative historical control subjects. No subject experienced a sustained
      change in CD4(+) cell count or HIV RNA level. The cellular infiltrate in biopsy
      samples obtained from the HIV-seropositive and HIV-seronegative subjects did not
      differ with respect to the percentage of leukocytes, neutrophils, macrophages, or
      T cells. The CD4(+):CD8(+) cell ratio in biopsy samples from the HIV-seropositive
      subjects was 1:3, the inverse of the ratio seen in the HIV-seronegative subjects
      (P<.0001). Although CD4(+) cells proliferated in lesions, in situ hybridization
      and reverse-transcription polymerase chain reaction for HIV RNA was negative. We
      conclude that experimental infection in HIV-seropositive persons is clinically
      similar to infection in HIV-seronegative persons and does not cause local or
      augment systemic viral replication. Thus, prompt treatment of chancroid may
      abrogate increases in viral replication associated with natural disease.

PMID- 17436225
TI  - Evolution of innate and adaptive effector cell functions during acute HIV-1
      infection.
AB  - Early events during acute human immunodeficiency virus type 1 (HIV-1) infection
      are critical in determining the course of disease progression. Cells of the
      innate and adaptive immune responses are involved in this acute response to
      infection; however, little is known about the coevolution of innate and adaptive
      effector cell populations during the initial phase of HIV-1 infection. Here, we
      have characterized the development of innate natural killer (NK) cell and
      adaptive HIV-1-specific CD8(+) T cell function during acute HIV-1 infection.
      Although NK cell populations were significantly expanded during acute infection
      before HIV-1 seroconversion, HIV-1-specific CD8(+) T cell responses were absent
      or weak and were inversely correlated with the level of NK cell activity. NK cell
      activity was directly correlated with the level of viral replication during acute
      HIV-1 infection and declined rapidly in subjects who initiated highly active
      antiretroviral therapy, whereas NK cell activity remained elevated in subjects
      who did not initiate therapy. Yet, reexposure to HIV-1 antigen during treatment
      discontinuation in chronic infection resulted in a synchronous increase in NK and
      CD8(+) T cell activity. Overall, these data demonstrate that expansion of the NK
      cell population precedes the development of adaptive HIV-1-specific CD8(+) T
      cells during acute infection but that both effector cell subsets respond with
      similar kinetics during chronic HIV-1 infection.

PMID- 17436226
TI  - HIV-1 infection of trophoblasts is independent of gp120/CD4 Interactions but
      relies on heparan sulfate proteoglycans.
AB  - Mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) is
      the leading cause of HIV infection in infants. Direct infection of trophoblasts-
      cells forming the placental barrier--may cause this transmission. Entry of HIV-1
      into trophoblasts is unusual for this retrovirus, because it is associated with
      endocytosis. However, given that trophoblasts express no or few
      receptors/coreceptors required for virus internalization, the mechanism
      underlying this event remains ambiguous. In the present study, we show that HIV-1
      entry and infection of polarized trophoblasts are independent not only of CD4 but
      also of envelope (Env) glycoproteins gp120 and gp41. Virus internalization,
      cytoplasmic release, reverse transcription, integration, and HIV-1 gene
      expression occurred with both fusion-incompetent and Env-deficient viruses.
      Importantly, fusion-independent infection was observed when we used viruses
      produced in a natural cellular reservoir (i.e., primary human cells). Finally,
      HIV-1 requires heparan sulfate proteoglycans for uptake in trophoblasts.
      Together, our findings illustrate that HIV-1 utilizes an unusual pathway for
      entering human polarized trophoblasts.

PMID- 17436227
TI  - Prevalence of factor H-binding protein variants and NadA among meningococcal
      group B isolates from the United States: implications for the development of a
      multicomponent group B vaccine.
AB  - BACKGROUND: Two promising recombinant meningococcal protein vaccines are in
      development. One contains factor H-binding protein (fHBP) variants (v.) 1 and 2,
      whereas the other contains v.1 and 4 other antigens discovered by genome mining
      (5 component [5C]). Antibodies against fHBP are bactericidal against strains
      within a variant group. There are limited data on the prevalence of strains
      expressing different fHBP variants in the United States. METHODS: A total of 143
      group B isolates from patients hospitalized in the United States were tested for
      fHBP variant by quantitative polymerase chain reaction, for reactivity with 6
      anti-fHBP monoclonal antibodies (MAb) by dot immunoblotting, and for
      susceptibility to bactericidal activity of mouse antisera. RESULTS: fHBP v.1
      isolates predominated in California (83%), whereas isolates expressing v.1 (53%)
      or v.2 (42%) were common in 9 other states. Isolates representative of 5 anti
      fHBP MAb-binding phenotypes (70% of isolates) were highly susceptible to anti
      fHBP v.1 or v.2 bactericidal activity, whereas 3 phenotypes were approximately
      50% susceptible. Collectively, antibodies against the fHBP v.1 and v.2 vaccine
      and the 5C vaccine killed 76% and 83% of isolates, respectively. CONCLUSIONS:
      Susceptibility to bactericidal activity can be predicted, in part, on the basis
      of fHBP phenotypes. Both vaccines have the potential to prevent most group B
      disease in the United States.

PMID- 17436228
TI  - Dose dependence of emergence of resistance to linezolid in Enterococcus faecalis
      in vivo.
AB  - BACKGROUND: The emergence of resistance to antibiotics in vivo, particularly in
      commensal, potentially pathogenic bacteria, is a factor that is key to the future
      of antibiotics. To better document the circumstances favoring the emergence of
      resistance to linezolid (the first of a new class of antibiotics, the
      oxazolidinones), we modeled the effect of different regimens of linezolid on
      Enterococcus faecalis in gnotobiotic mice. METHODS: We studied the rate of
      emergence of linezolid-resistant E. faecalis mutants in the digestive tract of
      gnotobiotic mice monoassociated with linezolid-susceptible E. faecalis and fed
      with water containing linezolid (0.5, 0.05, or 0.005 g/L). 23S Ribosomal RNA
      (rRNA) mutations were characterized by sequencing each of the 4 copies of the
      rRNA genes individually. RESULTS: Mutants were readily obtained in vivo, but the
      frequencies, persistence, and type of mutants were all dependent on the linezolid
      regimen. Mutations conferring resistance, either the G2505A or G2576U mutation,
      were present in domain V of the 23S rRNA gene of all resistant isolates. Levels
      of resistance increased with the number of mutated copies of the 23S rRNA gene
      and with duration of exposure. CONCLUSION: The antibiotic dose appears to be
      critical in the dynamics and molecular basis of resistance.

PMID- 17436229
TI  - Anti-tumor necrosis factor-alpha treatment activates Borrelia burgdorferi
      spirochetes 4 weeks after ceftriaxone treatment in C3H/He mice.
AB  - BACKGROUND: The effect of anti-tumor necrosis factor (TNF)-alpha treatment in
      Borrelia burgdorferi-infected and ceftriaxone-treated C3H/He mice was evaluated.
      METHODS: Mice were infected with B. garinii A218 or B. burgdorferi sensu stricto
      N40. At 2 weeks of infection, one group was treated simultaneously with
      ceftriaxone and anti-TNF-alpha, whereas another received ceftriaxone at 2 weeks
      and anti-TNF-alpha 4 weeks later. One group received ceftriaxone treatment only.
      Infected and noninfected control groups were sham treated. RESULTS: At 14 weeks
      of infection, B. burgdorferi could not be detected by cultivation or by
      polymerase chain reaction in tissue samples of any mouse treated with ceftriaxone
      only. However, spirochetes grew from the tissue samples of one-third of the mice
      treated with anti-TNF-alpha simultaneously or 4 weeks after ceftriaxone. These
      activated spirochetes showed ceftriaxone sensitivity rates, plasmid profiles, and
      virulence rates similar to those of bacteria used to infect the mice. All
      infected control mice and mice given anti-TNF-alpha only were culture positive.
      CONCLUSIONS: This report shows that, after ceftriaxone treatment for 5 days, a
      portion of B. burgdorferi-infected mice still have live spirochetes in their
      body, which are activated by anti-TNF-alpha treatment.

PMID- 17436230
TI  - High-cholesterol diet facilitates Anaplasma phagocytophilum infection and up
      regulates macrophage inflammatory protein-2 and CXCR2 expression in
      apolipoprotein E-deficient mice.
AB  - BACKGROUND: Anaplasma phagocytophilum is an obligatory intracellular bacterium
      that infects granulocytes and causes human granulocytic anaplasmosis (HGA). This
      bacterium requires cholesterol for host cell infection in vitro and incorporates
      exogenous cholesterol into its membrane. METHODS: To understand the role of host
      cholesterol in A. phagocytophilum infection in vivo, we analyzed the effects of a
      high-cholesterol diet and reduced apolipoprotein E (apoE) activity on A.
      phagocytophilum infection in mice. RESULTS: A high-cholesterol diet significantly
      facilitated A. phagocytophilum infection in the spleen, liver, and blood of apoE
      deficient (apoE(-/-)) mice, compared with the level of infection in apoE(-/-)
      mice fed a normal-cholesterol diet or wild-type (WT) mice fed a high- or normal
      cholesterol diet. A. phagocytophilum infection induced a significant elevation in
      the mRNA expression of macrophage inflammatory protein (MIP)-2 and an MIP-2
      receptor, CXCR2, in the spleen in apoE(-/-) mice fed a high-cholesterol diet,
      compared with the other 3 groups. CONCLUSION: Our results suggest that high blood
      cholesterol levels resulting from an interaction between dietary and genetic
      factors facilitate A. phagocytophilum infection and up-regulate a proinflammatory
      chemokine and its receptor, which may contribute to HGA pathogenesis.

PMID- 17436231
TI  - Immune suppression in advanced chronic fascioliasis: an experimental study in a
      rat model.
AB  - Chronicity and Th2 immune responses are features of helminth infections in
      humans. The liver fluke promotes its own survival through several strategies to
      down-regulate the immune response of the host during the early phase of
      infection. However, there is no evidence that this modulation occurs much later.
      The immune response in advanced chronic fascioliasis was analyzed in an
      experimental rat model at 20 weeks after infection. Cytokine quantification in
      infected rat serum revealed basal levels. The predominant immunoglobulin (Ig)
      isotype was IgG1. Flow cytometry analysis of T cell (CD3(+), CD4(+), and
      CD8a(+)), B cell (CD45R(+)), and macrophage (CD11b(+)) populations in spleens
      showed no significant differences between infected and control rats. Mononuclear
      cell proliferation in the spleen in response to T and B mitogens was strongly
      inhibited in infected versus control rats. During early chronic infection, there
      is a predominance of a Th2 response, which decreases in advanced chronic
      infection characterized by a persistent immune suppression.

PMID- 17436232
TI  - Control of Trypanosoma evansi infection is IgM mediated and does not require a
      type I inflammatory response.
AB  - Very recent reports have documented that Trypanosoma evansi, the etiological
      agent of the livestock disease "surra," can cause human trypanosomiasis. In
      contrast to trypanosomes causing human African trypanosomiasis, T. evansi has a
      wide geographic distribution and host range, yet information about the
      immunobiological aspects of T. evansi trypanosomiasis is limited. Here, we show
      that, although T. evansi causes the induction of tumor necrosis factor (TNF),
      interferon-gamma, and nitric oxide during the early stage of infection, none of
      these molecules are crucial for parasitemia control and survival of the infected
      animal. However, TNF and TNF receptor 2 affect the induction of late-stage
      anemia. Using B cell- and immunoglobulin M (IgM)-deficient mice, we identified
      IgM as being crucial for parasitemia control and host survival. Collectively, our
      results show that, compared with other trypanosomes, T. evansi displays a
      distinct host-parasite interaction profile, give that, despite an infection
      associated induction of proinflammatory molecules, only IgM antibodies contribute
      significantly to parasite control.

PMID- 17436233
TI  - A Duffy binding-like domain is involved in the NKp30-mediated recognition of
      Plasmodium falciparum-parasitized erythrocytes by natural killer cells.
AB  - The recent demonstration that purified natural killer (NK) cells lyse Plasmodium
      falciparum-parasitized red blood cells (Pf-pRBCs) suggests that innate immunity
      is important in malaria. NK cell killing--presumably an early host response to
      infection--requires intimate contact between NK natural cytotoxicity receptors
      (NCRs) and ligands expressed on the surface of Pf-pRBCs. We investigated whether
      the Duffy binding-like (DBL)-1 alpha domain of P. falciparum erythrocyte membrane
      protein-1 (PfEMP-1) expressed on parasitized erythrocytes rendered Pf-pRBCs
      susceptible to NK cell lysis. We showed that with NKp30-immunoglobulin and NKp46
      immunoglobulin fusion proteins and DBL-1alpha peptides NCRs are involved in the
      NK cell-Pf-pRBC interaction. This interaction was direct, specific, and
      functional, leading to perforin production and granzyme B release. The prior
      treatment of NK cells with DBL-1 alpha peptides abolished both this interaction
      and killing activity, suggesting that DBL-1 alpha -NCRs interaction is the key
      recognition mechanism leading to parasite killing by NK cells.

PMID- 17436234
TI  - Immunopathogenesis of respiratory syncytial virus bronchiolitis.
AB  - BACKGROUND: The objective of this study was to elucidate the relation between
      respiratory syncytial virus (RSV) infection and cytokine/chemokine
      concentrations, as well as the impact that these factors have on the severity of
      bronchiolitis. METHODS: Children <24 months old who presented to the emergency
      department with clinical symptoms of bronchiolitis were prospectively enrolled in
      the study. Nasal-wash samples were analyzed to identify viral pathogens and to
      quantify RSV and cytokine/chemokine concentrations. Severe cases of disease were
      defined as those requiring hospitalization, and severity was further determined
      on the basis of the duration of supplemental-oxygen and/or intravenous-fluid
      therapy. RESULTS: A total of 101 children were enrolled, 63 of whom were infected
      with RSV and 13 of whom were infected with other respiratory viruses; in 22
      children, no virus was detected. RSV bronchiolitis was associated with a greater
      inflammatory response than was non-RSV bronchiolitis, although RSV infection was
      not associated with more-severe disease. Levels of interleukin (IL)-6, IL-8, IL
      10, interferon (IFN)-gamma, and macrophage inflammatory protein (MIP)-1beta were
      significantly inversely correlated with the duration of supplemental-oxygen
      therapy. CONCLUSION: The robust inflammatory response associated with RSV
      infection does not contribute to the severity of RSV bronchiolitis any more than
      it contributes to the severity of non-RSV bronchiolitis. Elevated levels of
      proinflammatory mediators IL-6, IL-8, IFN-gamma, and MIP-1beta, as well as of the
      regulatory cytokine IL-10, may be protective against hypoxia in bronchiolitis.

PMID- 17436235
TI  - Hantavirus infection induces a typical myocarditis that may be responsible for
      myocardial depression and shock in hantavirus pulmonary syndrome.
AB  - Despite clinical evidence of myocardial dysfunction, there is no pathological
      evidence of myocardial injury in hantavirus pulmonary syndrome (HPS). The
      dominant opinion is that the primary cardiac lesion is functional rather than
      structural. The present study describes hantaviral antigen and particles in the
      cardiac endothelium and interstitial macrophages in association with a typical
      myocarditis in HPS. Human hearts from 14 individuals who died of HPS were
      compared with hearts from 14 individuals who died of acute necrotizing
      pancreatitis associated with acute lung injury and 4 individuals who died
      accidental deaths without thoracic injury (as controls); all cases were selected
      from autopsies. Transmural blocks of myocardial tissue were excised from the
      middle portion of the left-ventricular free wall and fixed in formalin. Small
      samples of myocardial tissue from 4 HPS cases and 4 non-HPS controls were fixed
      in glutaraldehyde for electron microscopic study. Histomorphometric,
      immunohistochemical, and ultrastructural methods were employed to detect the
      presence of hantavirus in the myocardium and to evaluate interstitial edema and
      the minor diameter of myocytes, to characterize the immunophenotype, and to
      estimate the number of inflammatory cells and in situ cytokine-producing cells
      and the T helper cell subset 1 and 2 immune responses (tumor necrosis factor
      [TNF]-alpha, interferon-gamma, interleukin [IL]-10, and IL-4). Cardiac
      remodeling; hantaviral antigen and particles in the endothelium and macrophages;
      scattered foci of myofiber necrosis; greater interstitial cellular infiltration,
      mainly composed of macrophages and memory T lymphocytes and a significant number
      of T helper and B lymphocytes; and TNF-alpha protein expression in macrophage
      type cells and cardiomyocytes were observed to a greater extent in HPS myocardium
      than in normal and acute pancreatitis control myocardium. These findings give
      support to the opinion that structural changes could be responsible for
      myocardial depression and shock in HPS, and it should be properly named as
      "hantavirus cardiopulmonary syndrome" (HCPS).

PMID- 17436237
TI  - Malnutrition and variability in CD4+ cell counts in African populations.

PMID- 17436239
TI  - The methylenetetrahydrofolate reductase 677C-->T polymorphism as a modulator of a
      B vitamin network with major effects on homocysteine metabolism.
AB  - Folates are carriers of one-carbon units and are metabolized by 5,10
      methylenetetrahydrofolate reductase (MTHFR) and other enzymes that use
      riboflavin, cobalamin, or vitamin B6 as cofactors. These B vitamins are essential
      for the remethylation and transsulfuration of homocysteine, which is an important
      intermediate in one-carbon metabolism. We studied the MTHFR 677C-->T polymorphism
      and B vitamins as modulators of one-carbon metabolism in 10,601 adults from the
      Norwegian Colorectal Cancer Prevention (NORCCAP) cohort, using plasma total
      homocysteine (tHcy) as the main outcome measure. Mean concentrations of plasma
      tHcy were 10.4 micromol/liter, 10.9 micromol/liter, and 13.3 micromol/liter in
      subjects with the CC (51%), CT (41%), and TT (8%) genotypes, respectively. The
      MTHFR 677C-->T polymorphism, folate, riboflavin, cobalamin, and vitamin B6 were
      independent predictors of tHcy in multivariate models (P<.001), and genotype
      effects were strongest when B vitamins were low (P<or=.006). Conversely, the
      MTHFR polymorphism influenced B vitamin effects, which were strongest in the TT
      group, in which the estimated tHcy difference between subjects with vitamin
      concentrations in the lowest compared with the highest quartile was 5.4
      micromol/liter for folate, 4.1 micromol/liter for riboflavin, 3.2 micromol/liter
      for cobalamin, and 2.1 micromol/liter for vitamin B6. Furthermore, interactions
      between B vitamins were observed, and B vitamins were more strongly related to
      plasma tHcy when concentrations of other B vitamins were low. The study provides
      comprehensive data on the MTHFR-B vitamin network, which has major effects on the
      transfer of one-carbon units. Individuals with the TT genotype were particularly
      sensitive to the status of several B vitamins and might be candidates for
      personalized nutritional recommendations.

PMID- 17436238
TI  - Genetic factors in congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) is a relatively common birth defect
      associated with high mortality and morbidity. Although the exact etiology of most
      cases of CDH remains unknown, there is a growing body of evidence that genetic
      factors play an important role in the development of CDH. In this review, we
      examine key findings that are likely to form the basis for future research in
      this field. Specific topics include a short overview of normal and abnormal
      diaphragm development, a discussion of syndromic forms of CDH, a detailed review
      of chromosomal regions recurrently altered in CDH, a description of the retinoid
      hypothesis of CDH, and evidence of the roles of specific genes in the development
      of CDH.

PMID- 17436240
TI  - Genetic linkage to chromosome 22q12 for a heavy-smoking quantitative trait in two
      independent samples.
AB  - We conducted a genomewide linkage screen of a simple heavy-smoking quantitative
      trait, the maximum number of cigarettes smoked in a 24-h period, using two
      independent samples: 289 Australian and 155 Finnish nuclear multiplex families,
      all of which were of European ancestry and were targeted for DNA analysis by use
      of probands with a heavy-smoking phenotype. We analyzed the trait, using a
      regression of identity-by-descent allele sharing on the sum and difference of the
      trait values for relative pairs. Suggestive linkage was detected on chromosome 22
      at 27-29 cM in each sample, with a LOD score of 5.98 at 26.96 cM in the combined
      sample. After additional markers were used to localize the signal, the LOD score
      was 5.21 at 25.46 cM. To assess the statistical significance of the LOD score in
      the combined sample, 1,000 simulated genomewide screens were conducted, resulting
      in an empirical P value of .006 for the LOD score of 5.21. This linkage signal is
      driven mainly by the microsatellite marker D22S315 (22.59 cM), which had a single
      point LOD score of 5.41 in the combined sample and an empirical P value <.001
      from 1,000 simulated genomewide screens. This marker is located within an intron
      of the gene ADRBK2, encoding the beta-adrenergic receptor kinase 2. Fine mapping
      of this linkage region may reveal variants contributing to heaviness of smoking,
      which will lead to a better understanding of the genetic mechanisms underlying
      nicotine dependence.

PMID- 17436241
TI  - Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and
      smoking in two subsets of rheumatoid arthritis.
AB  - Gene-gene and gene-environment interactions are key features in the development
      of rheumatoid arthritis (RA) and other complex diseases. The aim of this study
      was to use and compare three different definitions of interaction between the two
      major genetic risk factors of RA--the HLA-DRB1 shared epitope (SE) alleles and
      the PTPN22 R620W allele--in three large case-control studies: the Swedish
      Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, the North
      American RA Consortium (NARAC) study, and the Dutch Leiden Early Arthritis Clinic
      study (in total, 1,977 cases and 2,405 controls). The EIRA study was also used to
      analyze interactions between smoking and the two genes. "Interaction" was defined
      either as a departure from additivity, as interaction in a multiplicative model,
      or in terms of linkage disequilibrium--for example, deviation from independence
      of penetrance of two unlinked loci. Consistent interaction, defined as departure
      from additivity, between HLA-DRB1 SE alleles and the A allele of PTPN22 R620W was
      seen in all three studies regarding anti-CCP-positive RA. Testing for
      multiplicative interactions demonstrated an interaction between the two genes
      only when the three studies were pooled. The linkage disequilibrium approach
      indicated a gene-gene interaction in EIRA and NARAC, as well as in the pooled
      analysis. No interaction was seen between smoking and PTPN22 R620W. A new pattern
      of interactions is described between the two major known genetic risk factors and
      the major environmental risk factor concerning the risk of developing anti-CCP
      positive RA. The data extend the basis for a pathogenetic hypothesis for RA
      involving genetic and environmental factors. The study also raises and
      illustrates principal questions concerning ways to define interactions in complex
      diseases.

PMID- 17436242
TI  - Nova2 interacts with a cis-acting polymorphism to influence the proportions of
      drug-responsive splice variants of SCN1A.
AB  - An intronic polymorphism in the SCN1A gene, which encodes a neuronal sodium
      channel alpha subunit, has been previously associated with the dosing of two
      commonly used antiepileptic drugs that elicit their pharmacologic action
      primarily at this ion-channel subunit. This study sought to characterize the
      functional effects of this polymorphism on alternative splicing of SCN1A and to
      explore the potential for modulating the drug response in the pharmacologically
      unfavorable genotype by identification of a splice modifier acting on SCN1A. The
      effects of the genotype at the SCN1A IVS5N+5 G-->A polymorphism on SCN1A splice
      variant proportions and the consequences of increased expression of splice
      modifiers were investigated both in human temporal neocortex tissue and in a
      cellular minigene expression system. Quantitative real-time polymerase chain
      reaction was used to quantify the amounts of SCN1A transcripts forms. We show
      that the polymorphism has a dramatic effect on the proportions of neonate and
      adult alternative transcripts of SCN1A in adult brain tissue and that the effect
      of the polymorphism also appears to be modified by Nova2 expression levels. A
      minigene expression system confirms both the effect of the polymorphism on
      transcript proportions and the role of Nova2 in the regulation of splicing, with
      higher Nova2 expression increasing the proportion of the neonate form. A larger
      Nova2-mediated effect was detected in the AA genotype that is associated with
      increased dose requirements. The effects of Nova2 on modulation of the
      alternative splicing of 17 other neuronally expressed genes were investigated,
      and no effect was observed. These findings emphasize the emerging role of genetic
      polymorphisms in modulation of drug effect and illustrate both alternative
      splicing as a potential therapeutic target and the importance of considering the
      activity of compounds at alternative splice forms of drug targets in screening
      programs.

PMID- 17436243
TI  - The Himalayas as a directional barrier to gene flow.
AB  - High-resolution Y-chromosome haplogroup analyses coupled with Y-short tandem
      repeat (STR) haplotypes were used to (1) investigate the genetic affinities of
      three populations from Nepal--including Newar, Tamang, and people from
      cosmopolitan Kathmandu (referred to as "Kathmandu" subsequently)--as well as a
      collection from Tibet and (2) evaluate whether the Himalayan mountain range
      represents a geographic barrier for gene flow between the Tibetan plateau and the
      South Asian subcontinent. The results suggest that the Tibetans and Nepalese are
      in part descendants of Tibeto-Burman-speaking groups originating from Northeast
      Asia. All four populations are represented predominantly by haplogroup O3a5-M134
      derived chromosomes, whose Y-STR-based age (+/-SE) was estimated at 8.1+/-2.9
      thousand years ago (KYA), more recent than its Southeast Asian counterpart. The
      most pronounced difference between the two regions is reflected in the opposing
      high-frequency distributions of haplogroups D in Tibet and R in Nepal. With the
      exception of Tamang, both Newar and Kathmandu exhibit considerable similarities
      to the Indian Y-haplogroup distribution, particularly in their haplogroup R and H
      composition. These results indicate gene flow from the Indian subcontinent and,
      in the case of haplogroup R, from Eurasia as well, a conclusion that is also
      supported by the admixture analysis. In contrast, whereas haplogroup D is
      completely absent in Nepal, it accounts for 50.6% of the Tibetan Y-chromosome
      gene pool. Coalescent analyses suggest that the expansion of haplogroup D
      derivatives--namely, D1-M15 and D3-P47 in Tibet--involved two different
      demographic events (5.1+/-1.8 and 11.3+/-3.7 KYA, respectively) that are more
      recent than those of D2-M55 representatives common in Japan. Low frequencies,
      relative to Nepal, of haplogroup J and R lineages in Tibet are also consistent
      with restricted gene flow from the subcontinent. Yet the presence of haplogroup
      O3a5-M134 representatives in Nepal indicates that the Himalayas have been
      permeable to dispersals from the east. These genetic patterns suggest that this
      cordillera has been a biased bidirectional barrier.

PMID- 17436244
TI  - Hypomorphic mutations in the gene encoding a key Fanconi anemia protein, FANCD2,
      sustain a significant group of FA-D2 patients with severe phenotype.
AB  - FANCD2 is an evolutionarily conserved Fanconi anemia (FA) gene that plays a key
      role in DNA double-strand-type damage responses. Using complementation assays and
      immunoblotting, a consortium of American and European groups assigned 29 patients
      with FA from 23 families and 4 additional unrelated patients to complementation
      group FA-D2. This amounts to 3%-6% of FA-affected patients registered in various
      data sets. Malformations are frequent in FA-D2 patients, and hematological
      manifestations appear earlier and progress more rapidly when compared with all
      other patients combined (FA-non-D2) in the International Fanconi Anemia Registry.
      FANCD2 is flanked by two pseudogenes. Mutation analysis revealed the expected
      total of 66 mutated alleles, 34 of which result in aberrant splicing patterns.
      Many mutations are recurrent and have ethnic associations and shared allelic
      haplotypes. There were no biallelic null mutations; residual FANCD2 protein of
      both isotypes was observed in all available patient cell lines. These analyses
      suggest that, unlike the knockout mouse model, total absence of FANCD2 does not
      exist in FA-D2 patients, because of constraints on viable combinations of FANCD2
      mutations. Although hypomorphic mutations arie involved, clinically, these
      patients have a relatively severe form of FA.

PMID- 17436245
TI  - Improving power in contrasting linkage-disequilibrium patterns between cases and
      controls.
AB  - Genetic association studies offer an opportunity to find genetic variants
      underlying complex human diseases. The success of this approach depends on the
      linkage disequilibrium (LD) between markers and the disease variant(s) in a local
      region of the genome. Because, in the region with a disease mutation, the LD
      pattern among markers may differ between cases and controls, in some scenarios,
      it is useful to compare a measure of this LD, to map disease mutations. For
      example, using the composite correlation to characterize the LD among markers,
      Zaykin et al. recently suggested an "LD contrast" test and showed that it has
      high power under certain haplotype-driven disease models. Furthermore, it is
      likely that individual variants observed at different positions in a gene act
      jointly with each other to influence the phenotype, and the LD contrast test is
      also a useful method to detect such joint action. However, the LD among markers
      introduced by mutations and their joint action is usually confounded by
      background LD, which is measured at the population level, especially in a local
      region with disease mutations. Because the measures of LD that are usually used,
      such as the composite correlation, represent both effects, they may not be
      optimal for the purpose of detecting association when high background LD exists.
      Here, we describe a test that improves the LD contrast test by taking into
      account the background LD. Because the proposed test is developed in a regression
      framework, it is very flexible and can be extended to continuous traits and to
      incorporate covariates. Our simulation results demonstrate the validity and
      substantially higher power of the proposed method over current methods. Finally,
      we illustrate our new method by applying it to real data from the International
      Collaborative Study on Hypertension in Blacks.

PMID- 17436246
TI  - A simple and improved correction for population stratification in case-control
      studies.
AB  - Population stratification remains an important issue in case-control studies of
      disease-marker association, even within populations considered to be genetically
      homogeneous. Campbell et al. (Nature Genetics 2005;37:868-872) illustrated this
      by showing that stratification induced a spurious association between the lactase
      gene (LCT) and tall/short status in a European American sample. Furthermore,
      existing approaches for controlling stratification by use of substructure
      informative loci (e.g., genomic control, structured association, and principal
      components) could not resolve this confounding. To address this problem, we
      propose a simple two-step procedure. In the first step, we model the odds of
      disease, given data on substructure-informative loci (excluding the test locus).
      For each participant, we use this model to calculate a stratification score,
      which is that participant's estimated odds of disease calculated using his or her
      substructure-informative-loci data in the disease-odds model. In the second step,
      we assign subjects to strata defined by stratification score and then test for
      association between the disease and the test locus within these strata. The
      resulting association test is valid even in the presence of population
      stratification. Our approach is computationally simple and less model dependent
      than are existing approaches for controlling stratification. To illustrate these
      properties, we apply our approach to the data from Campbell et al. and find no
      association between the LCT locus and tall/short status. Using simulated data, we
      show that our approach yields a more appropriate correction for stratification
      than does principal components or genomic control.

PMID- 17436247
TI  - Phosphoserine aminotransferase deficiency: a novel disorder of the serine
      biosynthesis pathway.
AB  - We present the first two identified cases of phosphoserine aminotransferase
      deficiency. This disorder of serine biosynthesis has been identified in two
      siblings who showed low concentrations of serine and glycine in plasma and
      cerebrospinal fluid. Clinically, the index patient presented with intractable
      seizures, acquired microcephaly, hypertonia, and psychomotor retardation and died
      at age 7 mo despite supplementation with serine (500 mg/kg/d) and glycine (200
      mg/kg/d) from age 11 wk. The younger sibling received treatment from birth, which
      led to a normal outcome at age 3 years. Measurement of phosphoserine
      aminotransferase activity in cultured fibroblasts in the index patient was
      inconclusive, but mutational analysis revealed compound heterozygosity for two
      mutations in the PSAT1 gene--one frameshift mutation (c.delG107) and one missense
      mutation (c.299A-->C [p.Asp100Ala])--in both siblings. Expression studies of the
      p.Asp100Ala mutant protein revealed a V(max) of only 15% of that of the wild-type
      protein.

PMID- 17436248
TI  - Recurrent 10q22-q23 deletions: a genomic disorder on 10q associated with
      cognitive and behavioral abnormalities.
AB  - Low-copy repeats (LCRs) are genomic features that affect chromosome stability and
      can produce disease-associated rearrangements. We describe members of three
      families with deletions in 10q22.3-q23.31, a region harboring a complex set of
      LCRs, and demonstrate that rearrangements in this region are associated with
      behavioral and neurodevelopmental abnormalities, including cognitive impairment,
      autism, hyperactivity, and possibly psychiatric disease. Fine mapping of the
      deletions in members of all three families by use of a custom 10q oligonucleotide
      array-based comparative genomic hybridization (NimbleGen) and polymerase chain
      reaction-based methods demonstrated a different deletion in each family. In one
      proband, the deletion breakpoints are associated with DNA fragments containing
      noncontiguous sequences of chromosome 10, whereas, in the other two families, the
      breakpoints are within paralogous LCRs, removing approximately 7.2 Mb and 32
      genes. Our data provide evidence that the 10q22-q23 genomic region harbors one or
      more genes important for cognitive and behavioral development and that recurrent
      deletions affecting this interval define a novel genomic disorder.

PMID- 17436249
TI  - Measuring European population stratification with microarray genotype data.
AB  - A proper understanding of population genetic stratification--differences in
      individual ancestry within a population--is crucial in attempts to find genes for
      complex traits through association mapping. We report on genomewide typing of
      approximately 10,000 single-nucleotide polymorphisms in 297 individuals, to
      explore population structure in Europeans of known and unknown ancestry. The
      results reveal the presence of several significant axes of stratification, most
      prominently in a northern-southeastern trend, but also along an east-west axis.
      We also demonstrate the selection and application of EuroAIMs (European ancestry
      informative markers) for ancestry estimation and correction. The Coriell
      Caucasian and CEPH (Centre d'Etude du Polymorphisme Humain) Utah sample panels,
      often used as proxies for European populations, are found to reflect different
      subsets of the continent's ancestry.

PMID- 17436250
TI  - CHD7 gene polymorphisms are associated with susceptibility to idiopathic
      scoliosis.
AB  - Idiopathic scoliosis (IS) is the most common spinal deformity in children, and
      its etiology is unknown. To refine the search for genes underlying IS
      susceptibility, we ascertained a new cohort of 52 families and conducted a follow
      up study of genomewide scans that produced evidence of linkage and association
      with 8q12 loci (multipoint LOD 2.77; P=.0028). Further fine mapping in the region
      revealed significant evidence of disease-associated haplotypes (P<1.0 x 10-4)
      centering over exons 2-4 of the CHD7 gene associated with the CHARGE (coloboma of
      the eye, heart defects, atresia of the choanae, retardation of growth and/or
      development, genital and/or urinary abnormalities, and ear abnormalities and
      deafness) syndrome of multiple developmental anomalies. Resequencing CHD7 exons
      and conserved intronic sequence blocks excluded coding changes but revealed at
      least one potentially functional polymorphism that is overtransmitted (P=.005) to
      affected offspring and predicts disruption of a caudal-type (cdx) transcription
      factor binding site. Our results identify the first gene associated with IS
      susceptibility and suggest etiological overlap between the rare, early-onset
      CHARGE syndrome and common, later-onset IS.

PMID- 17436251
TI  - Mutations in cytokine receptor-like factor 1 (CRLF1) account for both Crisponi
      and cold-induced sweating syndromes.
AB  - Crisponi syndrome is a rare autosomal recessive disorder characterized by
      congenital muscular contractions of facial muscles, with trismus in response to
      stimuli, dysmorphic features, bilateral camptodactyly, major feeding and
      respiratory difficulties, and access of hyperthermia leading to death in the
      first months of life. The overlap with Stuve-Wiedemann syndrome (SWS) is
      striking, but the two conditions differ in that congenital lower limb bowing is
      absent in Crisponi syndrome, whereas it is a cardinal feature of SWS. We report
      here the exclusion of the leukemia inhibitory factor receptor gene in Crisponi
      syndrome and the identification of homozygote or compound heterozygote cytokine
      receptor-like factor 1 (CRLF1) mutations in four children from three unrelated
      families. The four mutations were located in the immunoglobulin-like and type III
      fibronectin domains, and three of them predicted premature termination of
      translation. Using real-time quantitative polymerase chain reaction, we found a
      significant decrease in CRLF1 mRNA expression in patient fibroblasts, which is
      suggestive of a mutation-mediated decay of the abnormal transcript. CRLF1 forms a
      heterodimer complex with cardiotrophin-like cytokine factor 1, and this
      heterodimer competes with ciliary neurotrophic factor for binding to the ciliary
      neurotrophic factor receptor (CNTFR) complex. The identification of CRLF1
      mutations in Crisponi syndrome supports the key role of the CNTFR pathway in the
      function of the autonomic nervous system.

PMID- 17436252
TI  - Crisponi syndrome is caused by mutations in the CRLF1 gene and is allelic to cold
      induced sweating syndrome type 1.
AB  - Crisponi syndrome is a severe autosomal recessive condition that is
      phenotypically characterized by abnormal, paroxysmal muscular contractions
      resembling neonatal tetanus, large face, broad nose, anteverted nares,
      camptodactyly, hyperthermia, and sudden death in most cases. We performed
      homozygosity mapping in five Sardinian and three Turkish families with Crisponi
      syndrome, using high-density single-nucleotide polymorphism arrays, and
      identified a critical region on chromosome 19p12-13.1. The most prominent
      candidate gene was CRLF1, recently found to be involved in the pathogenesis of
      cold-induced sweating syndrome type 1 (CISS1). CISS1 belongs to a group of
      conditions with overlapping phenotypes, also including cold-induced sweating
      syndrome type 2 and Stuve-Wiedemann syndrome. All these syndromes are caused by
      mutations of genes of the ciliary neurotrophic factor (CNTF)-receptor pathway.
      Here, we describe the identification of four different CRLF1 mutations in eight
      different Crisponi-affected families, including a missense mutation, a single
      nucleotide insertion, and a nonsense and an insertion/deletion (indel) mutation,
      all segregating with the disease trait in the families. Comparison of the
      mutation spectra of Crisponi syndrome and CISS1 suggests that neither the type
      nor the location of the CRLF1 mutations points to a phenotype/genotype
      correlation that would account for the most severe phenotype in Crisponi
      syndrome. Other, still-unknown molecular factors may be responsible for the
      variable phenotypic expression of the CRLF1 mutations. We suggest that the
      syndromes can comprise a family of "CNTF-receptor-related disorders," of which
      Crisponi syndrome would be the newest member and allelic to CISS1.

PMID- 17436253
TI  - Mutations in ZDHHC9, which encodes a palmitoyltransferase of NRAS and HRAS, cause
      X-linked mental retardation associated with a Marfanoid habitus.
AB  - We have identified one frameshift mutation, one splice-site mutation, and two
      missense mutations in highly conserved residues in ZDHHC9 at Xq26.1 in 4 of 250
      families with X-linked mental retardation (XLMR). In three of the families, the
      mental retardation phenotype is associated with a Marfanoid habitus, although
      none of the affected individuals meets the Ghent criteria for Marfan syndrome.
      ZDHHC9 is a palmitoyltransferase that catalyzes the posttranslational
      modification of NRAS and HRAS. The degree of palmitoylation determines the
      temporal and spatial location of these proteins in the plasma membrane and Golgi
      complex. The finding of mutations in ZDHHC9 suggests that alterations in the
      concentrations and cellular distribution of target proteins are sufficient to
      cause disease. This is the first XLMR gene to be reported that encodes a
      posttranslational modification enzyme, palmitoyltransferase. Furthermore, now
      that the first palmitoyltransferase that causes mental retardation has been
      identified, defects in other palmitoylation transferases become good candidates
      for causing other mental retardation syndromes.

PMID- 17436254
TI  - Mutations in TCF4, encoding a class I basic helix-loop-helix transcription
      factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic
      encephalopathy associated with autonomic dysfunction.
AB  - Pitt-Hopkins syndrome (PHS) is a rare syndromic encephalopathy characterized by
      daily bouts of hyperventilation and a facial gestalt. We report a 1.8-Mb de novo
      microdeletion on chromosome 18q21.1, identified by array-comparative genomic
      hybridization in one patient with PHS. We subsequently identified two de novo
      heterozygous missense mutations of a conserved amino acid in the basic region of
      the TCF4 gene in three additional subjects with PHS. These findings demonstrate
      that TCF4 anomalies are responsible for PHS and provide the first evidence of a
      human disorder related to class I basic helix-loop-helix transcription-factor
      defects (also known as "E proteins"). Moreover, our data may shed new light on
      the normal processes underlying autonomic nervous system development and
      maintenance of an appropriate ventilatory neuronal circuitry.

PMID- 17436255
TI  - Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent
      hyperventilation (Pitt-Hopkins syndrome).
AB  - Pitt-Hopkins syndrome is a rarely reported syndrome of so-far-unknown etiology
      characterized by mental retardation, wide mouth, and intermittent
      hyperventilation. By molecular karyotyping with GeneChip Human Mapping 100K SNP
      arrays, we detected a 1.2-Mb deletion on 18q21.2 in one patient. Sequencing of
      the TCF4 transcription factor gene, which is contained in the deletion region, in
      30 patients with significant phenotypic overlap revealed heterozygous stop,
      splice, and missense mutations in five further patients with severe mental
      retardation and remarkable facial resemblance. Thus, we establish the Pitt
      Hopkins syndrome as a distinct but probably heterogeneous entity caused by
      autosomal dominant de novo mutations in TCF4. Because of its phenotypic overlap,
      Pitt-Hopkins syndrome evolves as an important differential diagnosis to Angelman
      and Rett syndromes. Both null and missense mutations impaired the interaction of
      TCF4 with ASCL1 from the PHOX-RET pathway in transactivating an E box-containing
      reporter construct; therefore, hyperventilation and Hirschsprung disease in
      patients with Pitt-Hopkins syndrome might be explained by altered development of
      noradrenergic derivatives.

PMID- 17436257
TI  - From a stable silylene to a mixed-valent disiloxane and an isolable silaformamide
      borane complex with considerable silicon-oxygen double-bond character.

PMID- 17436256
TI  - Description of core excitations by time-dependent density functional theory with
      local density approximation, generalized gradient approximation, meta-generalized
      gradient approximation, and hybrid functionals.
AB  - Time-dependent density functional theory (TDDFT) is employed to investigate
      exchange-correlation-functional dependence of the vertical core-excitation
      energies of several molecules including H, C, N, O, and F atoms. For the local
      density approximation (LDA), generalized gradient approximation (GGA), and meta
      GGA, the calculated X1s-->pi* excitation energies (X = C, N, O, and F) are
      severely underestimated by more than 13 eV. On the other hand, time-dependent
      Hartree-Fock (TDHF) overestimates the excitation energies by more than 6 eV. The
      hybrid functionals perform better than pure TDDFT because HF exchange remedies
      the underestimation of pure TDDFT. Among these hybrid functionals, the Becke-Half
      and-Half-Lee-Yang-Parr (BHHLYP) functional including 50% HF exchange provides the
      smallest error for core excitations. We have also discovered the systematic trend
      that the deviations of TDHF and TDDFT with the LDA, GGA, and meta-GGA functionals
      show a strong atom-dependence. Namely, their deviations become larger for heavier
      atoms, while the hybrid functionals are significantly less atom-dependent.

PMID- 17436258
TI  - Molecular dynamics simulations of Na+/Cl(-)-dependent neurotransmitter
      transporters in a membrane-aqueous system.
AB  - We have performed molecular dynamics simulations of a homology model of the human
      serotonin transporter (hSERT) in a membrane environment and in complex with
      either the natural substrate 5-HT or the selective serotonin reuptake inhibitor
      escitalopram. We have also included a transporter homologue, the Aquifex aeolicus
      leucine transporter (LeuT), in our study to evaluate the applicability of a
      simple and computationally attractive membrane system. Fluctuations in LeuT
      extracted from simulations are in good agreement with crystallographic B factors.
      Furthermore, key interactions identified in the X-ray structure of LeuT are
      maintained throughout the simulations indicating that our simple membrane system
      is suitable for studying the transmembrane protein hSERT in complex with 5-HT or
      escitalopram. For these transporter complexes, only relatively small fluctuations
      are observed in the ligand-binding cleft. Specific interactions responsible for
      ligand recognition, are identified in the hSERT-5HT and hSERT-escitalopram
      complexes. Our findings are in good agreement with predictions from mutagenesis
      studies.

PMID- 17436259
TI  - From modeling to medicinal chemistry: automatic generation of two-dimensional
      complex diagrams.
AB  - As a result of the increasing application of structure-based drug design, the
      visualization of protein-ligand complexes has become an important feature in
      medicinal chemistry. The large number of experimentally resolved complex
      structures and the further development of computer-aided methods like docking or
      de novo design establishes new possibilities in this field. During lead finding
      and optimization, a manual investigation of many complexes and their interaction
      patterns is typically performed. We present an algorithm that automatically
      generates 2D-protein-ligand diagrams as a possible solution for a transparent
      visualization of the contact partners in a complex and as a support for
      scientists in the evaluation of structure-based design results. Running the
      software on representative test data sets, it generates collision free layouts
      for approximately 76% of the cases in the range of tenths of a second per
      complex. The success rate for complexes with ligands which have a molecular
      weight <500 Da is 87%.

PMID- 17436260
TI  - Model systems for activation of nucleic acid encoded prodrugs.
AB  - The development of more selective chemotherapeutic agents for benign treatments
      of malicious diseases is highly desirable. In recent years model systems for the
      release of small molecule drugs from nucleic acid conjugates by templated
      chemical or photochemical reactions have been designed. Common for these systems
      is that the stoichiometric or catalytic drug release is controlled by the highly
      selective hybridization between complementary strands of nucleic acids. Herein,
      the concepts of the new field of nucleic acid templated release reactions are
      outlined.

PMID- 17436261
TI  - Angeli's salt (Na2N2O3) is a precursor of HNO and NO: a voltammetric study of the
      reactive intermediates released by Angeli's salt decomposition.
AB  - Under physiological conditions, it is usually accepted that the aerobic
      decomposition of Angeli's salt produces nitrite (NO(2)(-)) and nitroxyl (HNO),
      which dimerizes and leads to N(2)O. No consensus has yet been established on the
      formation of nitric oxide (NO) and/or peroxynitrite (ONOO(-)) by Angeli's salt.
      Because this salt has recently been shown to have pharmacological properties for
      the treatment of cardiovascular diseases, identification of its follow-up
      reactive intermediates is of increasing importance. In this work, we investigated
      the decomposition mechanism of Angeli's salt by voltammetry performed at
      platinized carbon fiber microelectrodes. By following the decomposition process
      of Angeli's salt, we showed that the mechanism depends on the experimental
      conditions. Under aerobic neutral and slightly alkaline conditions, the formation
      of HNO, NO(2)(-), but also of nitric oxide NO was demonstrated. In strongly
      alkaline buffer (pH>10), we observed the formation of peroxynitrite ONOO(-) in
      the presence of oxygen. These electrochemical results are supported by comparison
      with UV spectrophotometry data.

PMID- 17436262
TI  - A room-temperature liquid-crystalline phase with crystalline pi stacks.

PMID- 17436263
TI  - Charge-monitoring laser-induced acoustic desorption mass spectrometry for cell
      and microparticle mass distribution measurement.

PMID- 17436264
TI  - Differential recovery of membrane proteins after extraction by aqueous methanol
      and trifluoroethanol.
AB  - Cell membrane proteome analysis is limited by inherent membrane hydrophobicity.
      Conventional membrane protein extraction techniques use detergents, chaotropes
      and organic acids that require sample clean-up or pH adjustment, and are
      associated with significant sample loss. We extracted membrane proteins from red
      blood cells (RBCs) using methanol (MeOH), trifluoroethanol (TFE) and urea, and
      identified membrane proteins using 2-D LC coupled with MALDI-TOF/TOF-MS. We show
      that organic solvents MeOH- and TFE-based methods have membrane protein analysis
      efficiencies comparable to urea, and are complementary for the recovery of both
      hydrophilic and hydrophobic peptides. The mean grand average of hydropathicity
      (GRAVY) value of identified peptides from the TFE-based method (-0.107) was
      significantly higher than that of the MeOH-based method (-0.465) (p<0.001).
      Sequential and adjunctive use of the organic solvents MeOH and TFE increases the
      number of proteins identified, and the confidence of their identification. We
      show that this strategy is effective for shotgun membrane proteome analysis.

PMID- 17436265
TI  - Capturing and amplifying impurities from purified recombinant monoclonal
      antibodies via peptide library beads: a proteomic study.
AB  - Capture and amplification of low-level contaminants in purified preparations of
      recombinant DNA products is described here in the case of mAb meant for human
      consumption. Such a process is based on treatment with a vastly heterogeneous
      ligand library composed of hexapeptides bound to a polyhydroxymethacrylate resin.
      Upon this treatment, a protein solution is recovered with "normalized" relative
      concentration ratios, in which high-abundance proteins are strongly reduced and
      rare proteins are highly concentrated. Upon 2-D map analysis, the relatively few
      spots present in control monoclonals were seen to increase in number, reaching
      >100 visible polypeptide chains in the pI/M(r) plane. Most of these newly emerged
      spots were subjected to MS analysis and were found to be composed mainly of three
      classes of proteins: those derived from proteins present in the culture broth
      (notably albumin and transferrin), fragments of the desired final product,
      covering M(r) ranges from as low as 5 up to 45 kDa and some aggregates of light
      and heavy chains of Igs (mostly dimers and trimers). This ligand library thus
      appears to be a formidable tool for exploring and bringing to the limelight the
      "hidden proteome".

PMID- 17436266
TI  - Proteome analysis of whole saliva: a new tool for rheumatic diseases--the example
      of Sjogren's syndrome.
AB  - Sjogren's syndrome (pSS) is a systemic disease that affects salivary glands
      directly, and is therefore expected to influence the composition of human whole
      saliva (WS) fluid. The aim of this study was to characterize the WS proteins of
      pSS patients using a proteomic approach to assess a valid procedure to examine
      the global changes of the salivary protein profiles in connective tissue
      disorders. The WS proteins expressed in patients affected by pSS and healthy
      volunteers were analyzed using the 2-DE technique. The WS protein pattern was
      altered in pSS patients compared to controls, with a decrease in some of the
      typical salivary proteins. Particularly, a remarkable alteration of carbonic
      anhydrase VI was observed. Moreover, a comparison of WS protein profile of pSS
      patients with the one obtained from controls revealed a set of differentially
      expressed proteins. These proteins were related to acute and chronic inflammation
      while some others were involved in oxidative stress injury. These findings are in
      line with the systemic immuno-inflammatory aspects of pSS and open the
      possibility for a systematic search of diagnostic biomarkers and targets for
      therapeutic intervention in pSS.

PMID- 17436267
TI  - An improved strategy for selective and efficient enrichment of integral plasma
      membrane proteins of mycobacteria.
AB  - Mycobacterial plasma membrane proteins play essential roles in many cellular
      processes, yet their comprehensive proteomic profiling remains challenging. This
      is mainly due to obstacles related to their extraction and solubilization. To
      tackle this problem, we have developed a novel procedure to selectively enrich
      mycobacterial plasma membrane proteins based on alkaline sodium carbonate washing
      of crude membranes followed by Triton X-114 phase partitioning. The present study
      assesses the efficiency of this method by proteome analysis of plasma membrane
      proteins from Mycobacterium bovis BCG. Extracted proteins were separated in
      parallel by 1-D SDS-PAGE and 2-DE and then analyzed by LC-MS/MS and MALDI-MS/MS.
      Our study revealed 125 proteins, of which 54 contained 1-14 predicted
      transmembrane domains (TMD) including nine novel proteins. The 1-D SDS-PAGE-based
      proteome analysis identified 81 proteins, of which 49 (60.5%) harbored TMD. This
      approach also revealed many hydrophobic membrane-associated/periplasmic proteins
      lacking TMD, but only few soluble proteins. The identified proteins were
      characterized with regard to biological functions and physicochemical properties
      providing further evidence for the high efficiency of the prefractionation method
      described herein.

PMID- 17436268
TI  - Diabetes-induced changes in the renal cortical proteome assessed with two
      dimensional gel electrophoresis and mass spectrometry.
AB  - To understand the spectrum of proteins affected by diabetes and to characterize
      molecular functions and biological processes they control, we analyzed the renal
      cortical proteome of db/db mice using 2-DE combined with MALDI-TOF, MALDI
      TOF/TOF, and LC-MS/MS. This approach yielded 278 high confidence identifications
      whose expression levels were significantly increased or decreased >two-fold by
      diabetes, of which 170 mapped to gene identifiers representing 147 nonredundant
      proteins. Gene Ontology classification demonstrated that 80% of these proteins
      modulated physiological functions, 55% involved metabolism, approximately 25%
      involved carboxylic and organic acid metabolism, 14% involved biosynthesis or
      catabolism, and 12% involved fatty acid metabolism. Predominant molecular
      functions were catalytic (61%), oxidoreductase (20%), and transferase (17%)
      activities, and nucleotide and ATP binding (11-15%). Twenty eight percent of the
      proteins identified as significantly altered by diabetes were mitochondrial
      proteins. The top-ranked network described by Ingenuity Pathway Analysis
      indicated PPARalpha was the most common node of interaction for the numerous
      enzymes whose expression levels were influenced by diabetes. These differentially
      regulated proteins create a foundation for a systems biology exploration of
      molecular mechanisms underlying the pathophysiology of diabetic nephropathy.

PMID- 17436269
TI  - Frontiers in glycomics; bioinformatics and biomarkers in disease. September 11
      13, 2006 Natcher Conference Center, NIH Campus, Bethesda, MD, USA.
AB  - This is a short summary of a meeting entitled "The Frontiers in Glycomics;
      Bioinformatics and Biomarkers in Disease" which was jointly organized by the NIH
      Consortium for Functional Glycomics (CFG), Human Disease Glycomics/Proteome
      Initiative (HGPI), National Cancer Institute, National Institute of General
      Medical Sciences, Japan Society for the Promotion of Science and National Center
      for Research Resources held at the NIH Campus, Bethesda, MD, Natcher Conference
      Center in September 11-13, 2006.

PMID- 17436271
TI  - Neonatal rhabdomyoma causing right ventricular inflow obstruction with duct
      dependent pulmonary blood flow: successful stenting of PDA.
AB  - We describe an infant with the antenatal diagnosis of a large intracardiac
      rhabdomyoma causing tricuspid inflow obstruction. Postnatal cyanosis and arterial
      hypoxemia prompted commencement of intravenous prostaglandin E1 with immediate
      improvement in saturations. Clinical and genetic testing confirmed diagnosis of
      tuberous sclerosis. To secure ductal patency, two tandem coronary stents were
      implanted via an antegrade approach. Several episodes of long RP atrio
      ventricular re-entrant tachycardia were observed. At 7(1/2) months of age, the
      tumor was no longer obstructive to tricuspid inflow, ductal flow was highly
      restrictive and there was no recurrence of supraventricular tachycardia.

PMID- 17436272
TI  - Differential responses to the application of exogenous NT-3 are observed for
      subpopulations of motor and sensory neurons depending on the presence of skeletal
      muscle.
AB  - We examined the effects of a single injection of exogenous NT-3, administered at
      embryonic day (E) 13.5, on the survival of two populations of motor neurons and
      two populations of sensory neurons. Both wild-type and double knockout, Myf5-/
      :MyoD-/-, mutant embryos were examined to determine the effects of the
      aforementioned neurotrophin on motor and sensory neuron survival in the presence
      and absence, respectively, of skeletal muscle. We found that, although NT-3
      rescues select populations of motor neurons in the absence of muscles, there is a
      lack of increase in neuron survival when skeletal muscle is present.
      Additionally, NT-3 was found to rescue a select population of proprioceptive
      sensory neurons in the absence of target tissue, while, at times, exacerbating
      neuron cell death when target tissues are present. Lastly, we found that neurons
      in the spinal cord and brainstem show both a regional and functional specificity
      in their response to the administration of NT-3 in utero. Our results indicate
      the possibility that different pathways are involved in the survival of neurons
      during naturally occurring programmed cell death and during excessively occurring
      programmed cell death.

PMID- 17436273
TI  - Transient expression of thyroid hormone nuclear receptor TRbeta2 sets S opsin
      patterning during cone photoreceptor genesis.
AB  - Cone photoreceptors in the murine retina are patterned by dorsal repression and
      ventral activation of S opsin. TR beta 2, the nuclear thyroid hormone receptor
      beta isoform 2, regulates dorsal repression. To determine the molecular mechanism
      by which TR beta 2 acts, we compared the spatiotemporal expression of TR beta 2
      and S opsin from embryonic day (E) 13 through adulthood in C57BL/6 retinae. TR
      beta 2 and S opsin are expressed in cone photoreceptors only. Both are
      transcribed by E13, and their levels increase with cone genesis. TR beta 2 is
      expressed uniformly, but transiently, across the retina. mRNA levels are maximal
      by E17 at completion of cone genesis and again minimal before P5. S opsin is also
      transcribed by E13, but only in ventral cones. Repression in dorsal cones is
      established by E17, consistent with the occurrence of patterning during cone cell
      genesis. The uniform expression of TR beta 2 suggests that repression of S opsin
      requires other dorsal-specific factors in addition to TR beta 2. The mechanism by
      which TR beta 2 functions was probed in transgenic animals with TR beta 2
      ablated, TR beta 2 that is DNA binding defective, and TR beta 2 that is ligand
      binding defective. These studies show that TR beta 2 is necessary for dorsal
      repression, but not ventral activation of S opsin. TR beta 2 must bind DNA and
      the ligand T3 (thyroid hormone) to repress S opsin. Once repression is
      established, T3 no longer regulates dorsal S opsin repression in adult animals.
      The transient, embryonic action of TR beta 2 is consistent with a role (direct
      and/or indirect) in chromatin remodeling that leads to permanent gene silencing
      in terminally differentiated, dorsal cone photoreceptors.

PMID- 17436274
TI  - Age-specific association of steroid hormone pathway gene polymorphisms with
      breast cancer risk.
AB  - BACKGROUND: Breast cancer (BC) is a complex disease, and the incidence rates for
      BC increase with age. Both environmental factors and genetics have an impact on
      the risk of BC. Although the effects of environmental factors may vary with age,
      it has been assumed generally that the penetrance of single nucleotide
      polymorphisms (SNPs) is constant throughout life. In the current study, the
      results demonstrated that certain SNPs exhibit BC risk associations that vary
      considerably with age. METHODS: SNPs in 12 steroid hormone pathway genes were
      investigated for associations with BC risk in white women who were enrolled in an
      age-matched, case-control (1:2 for cases and controls, respectively) study that
      consisted of a discovery set (n = 5000 women) and an independent validation set
      (n = 1583 women). RESULTS: Significant age-related trends were identified and
      confirmed for SNPs in 4 genes associated with BC risk. The cytosine/cytosine
      (C/C) genotype of cytochrome P450 XIB2 (CYP11B2) was associated with decreased
      risk at younger ages (ages 30-44 years) but an increased risk at older ages (ages
      55-69 years). The homozygous cytosine-guanine (CG/CG) genotype of uridine
      phosphorylase glycosyltransferase 1A7 (UGT1A7) was associated with increased risk
      at younger ages but decreased risk at older ages. Associations in cytochrome P450
      19 (CYP19) and progesterone receptor (PGR) were confined to middle age (ages 45
      54 years). CONCLUSIONS: The identification of age-specific genetic associations
      may have profound implications for future etiologic studies of BC and for the use
      of SNP genotyping to accurately predict the risk of BC in women.

PMID- 17436275
TI  - Ras signaling modulates activity of the ecdysone receptor EcR during cell
      migration in the Drosophila ovary.
AB  - Ecdysone Receptor (EcR) mediates effects of the hormone ecdysone during larval
      molts, pupal metamorphosis, and adult female oogenesis. In the ovary, egg chamber
      formation requires interactions between the somatic follicle cell (FC) epithelium
      and the germ line nurse cell/oocyte cyst. Previous work has shown EcR is required
      in the germ line for egg chamber maturation, and here we examine EcR requirements
      in the FC at late stages of oogenesis. EcR protein is ubiquitous in the FC but
      its activity is restricted, visualized by activity of the "ligand sensor" hs-GAL4
      EcR ligand binding domain fusion and EcRE-lacZ reporter gene expression. GAL4-EcR
      is activated in the FC by an ecdysone agonist and repressed by tissue-specific
      Ras GTPase signals. To determine the significance of restricted sites of EcR
      activity in the FC, we used targeted misexpression of the dominant negative EcR
      (EcR-DN) molecules EcR(F645A) and EcR(W650A). EcR-DN expression at stage 10
      reduced EcRE-lacZ expression in the nurse cell FC and resulted in abnormal FC
      migrations, including aberrant centripetal migration and dorsal appendage tube
      formation, leading to the formation of cup-shaped eggs with shortened, branched
      dorsal appendages at stage 14. Clones of FC expressing EcR-DN displayed cell
      autonomous increases in DE-cadherin expression and abnormal epithelial junction
      formation. EcR-DN expression caused thin eggshell phenotypes that correlated with
      both reduced levels of chorion gene expression and reduction in chorion gene
      amplification. Our results indicate that tissue-specific modulation of EcR
      activity by the Ras signaling pathway refines temporal ecdysone signals that
      regulate FC differentiation and cadherin-mediated epithelial cell shape changes.

PMID- 17436276
TI  - Census of vertebrate Wnt genes: isolation and developmental expression of Xenopus
      Wnt2, Wnt3, Wnt9a, Wnt9b, Wnt10a, and Wnt16.
AB  - The Wnt family of growth factors regulate many different aspects of embryonic
      development. Assembly of the complete mouse and human genome sequences, plus
      expressed sequence tag surveys have established the existence of 19 Wnt genes in
      mammalian genomes. However, despite the importance of model vertebrates for
      studies in developmental biology, the complete complement of Wnt genes has not
      been established for nonmammalian genomes. Using genome sequences for chicken
      (Gallus gallus), frog (Xenopus tropicalis), and fish (Danio rerio and Tetraodon
      nigroviridis), we have analyzed gene synteny to identify the orthologues of all
      19 human Wnt genes in these species. We find that, in addition to the 19 Wnts
      observed in humans, chicken contained an additional Wnt gene, Wnt11b, which is
      orthologous to frog and zebrafish Wnt11 (silberblick). Frog and fish genomes
      contained orthologues of the 19 mammalian Wnt genes, plus Wnt11b and several
      duplicated Wnt genes. Specifically, the Xenopus tropicalis genome contained 24
      Wnt genes, including additional copies of Wnt7-related genes (Wnt7c) and 3 recent
      Wnt duplications (Wnt3, Wnt9b, and Wnt11). The Danio rerio genome contained 27
      Wnt genes with additional copies of Wnt2, Wnt2b, Wnt4b, Wnt6, Wnt7a, and Wnt8a.
      The presence of the additional Wnt11 sequence (Wnt11b) in the genomes of all
      ancestral vertebrates suggests that this gene has been lost during mammalian
      evolution. Through these studies, we identified the frog orthologues of the
      previously uncharacterized Wnt2, Wnt3, Wnt9a, Wnt9b, Wnt10a, and Wnt16 genes and
      their expression has been characterized during early Xenopus development.

PMID- 17436277
TI  - Nutritional endoderm in a direct developing frog: a potential parallel to the
      evolution of the amniote egg.
AB  - The egg of the direct-developing frog, Eleutherodactylus coqui, has 20 x the
      volume as that of the model amphibian, Xenopus laevis. Increased egg size led to
      the origin of nutritional endoderm, a novel cell type that provides nutrition but
      does not differentiate into digestive tract tissues. As the E. coqui endoderm
      develops, a distinct boundary exists between differentiating intestinal cells and
      large yolky cells, which persists even when yolk platelets are depleted. The
      yolky cells do not become tissues of the digestive tract and are lost, as shown
      by histology and lineage tracing. EcSox17, an endodermal transcriptional factor,
      did not distinguish these two cell types, however. When cleavage of the yolky
      cells was inhibited, embryogenesis continued, indicating that some degree of
      incomplete cleavage can be tolerated. The presence of cellularized nutritional
      endoderm in E. coqui may parallel changes that occurred in the evolution of the
      amniote egg 360 million years ago.

PMID- 17436278
TI  - Zebrafish dou yan mutation causes patterning defects and extensive cell death in
      the retina.
AB  - The size of an organ is largely determined by the number of cells it contains,
      which in turn is regulated by two opposing processes, cell proliferation and cell
      death, however, it is generally not clear how cell proliferation and cell death
      are coordinated during development. Here, we characterize the zebrafish dou
      yan(mi234) mutation that results in a dramatic reduction of retinal size and a
      disruption of retinal differentiation and lamination. The retinal size reduction
      is caused by increased retinal cell death in a non-cell-autonomous manner during
      early development. The phenotypic defect in dou yan(mi234) arises coincident with
      the onset of retinal neurogenesis and differentiation. Interestingly, unlike many
      other small eye mutations, the mutation does not increase the level of cell death
      in the brain, suggesting that the brain and retina use different mechanisms to
      maintain cell survival. Identification and further study of the dou yan gene will
      enhance our understanding of the molecular mechanisms regulating retinal cellular
      homeostasis, i.e., the balance between cell proliferation and cell death.

PMID- 17436279
TI  - Expression profile of Papss2 (3'-phosphoadenosine 5'-phosphosulfate synthase 2)
      during cartilage formation and skeletal development in the mouse embryo.
AB  - Sulfation of proteoglycans is a very important posttranslational modification in
      chondrocyte growth and development. The enzyme 3'-phosphoadenosine 5'
      phosphosulfate synthase (PAPSS) catalyzes the biosynthesis of PAPS (3'
      phosphoadenosine 5'-phosphosulfate), which serves as the universal sulfate donor
      compound for all sulfotransferase reactions (Schwartz and Domowicz [2002]
      Glycobiology 109:143-151). Two major isoenzymes, PAPS synthase 1 (PAPSS1) and
      PAPS synthase 2 (PAPSS2) were identified in higher organisms for the synthesis of
      PAPS. PAPSS1 is the more prominent isoform and is ubiquitously expressed in human
      adult tissues, including cartilage, while PAPSS2 shows a more restricted
      expression pattern and appears to be the major variant in growth plate cartilage
      (Fuda et al. [2002] Biochem J 365(Pt 2):497-504). Mutations within the murine and
      the human PAPSS2 genes are responsible for diseases affecting the skeletal system
      (Kurima et al. [1998] Proc Natl Acad Sci USA 95:8681-8685; ul Haque et al. [1998]
      Nat Genet 20:157-162), like the spondyloepimetaphyseal dysplasia (SEMD) Pakistani
      type. To further elucidate the function of Papss2 within the developing skeleton,
      we investigated the expression pattern of the murine gene at different
      developmental stages. We detected Papss2 mRNA starting from 11.5 days post coitum
      (dpc) at the sites of first chondrogenic condensations and the expression
      continued in all cartilaginous elements tested of 12.5 dpc, 13.5 dpc, 16.5 dpc
      embryos, and newborn mice. Papss2 transcripts were also observed in other tissues
      such as heart, tongue, kidney, and neuronal tissues. However, the most
      significant levels of Papss2 mRNA were found in condensing and proliferating
      chondrocytes, whereas hypertrophic chondrocytes show a dramatic down-regulation
      of Papss2 mRNA expression, indicating an important role of the gene product for
      cartilage growth and development in mouse embryo.

PMID- 17436280
TI  - Gene expression analysis of the hedgehog signaling cascade in the chick midbrain
      and spinal cord.
AB  - The signaling molecule Sonic Hedgehog (SHH) plays a critical role in patterning
      the ventral midbrain of vertebrates. Our recent studies have established that the
      requirement for Hedgehog (HH) signaling in the chick midbrain is modulated
      spatially and temporally in a complex manner across the midbrain anlage.
      Unfortunately, the patterns of expression of downstream regulators that might
      modulate the HH signal in the midbrain are not currently known. To fill this gap,
      we have examined across time, the expression pattern of 14 genes that function in
      the HH signaling cascade in the midbrain and spinal cord. Our results suggest
      that SHH expression in the axial mesendoderm begins before the expression of
      known HH receptors/HH-binding proteins (e.g., PTC1, PTC2, HHIP, BOC, MEGALIN). In
      the midbrain, PTC and GLI genes are expressed and then eliminated very early from
      the ventral midline. However, they exhibit high and persistent expression in the
      midbrain region circumscribing the SHH source. Intriguingly, multiple HH-binding
      proteins (BOC, MEGALIN) and HH effectors (GLI1-3, SMO, SUFU, DZIP) are expressed
      in the dorsal midbrain and the midbrain-hindbrain boundary. Finally, we report
      for the first time that IHH is expressed in intermediate regions of the spinal
      cord, where its expression does not overlap with that of SHH.

PMID- 17436282
TI  - Macaque monkey retrosplenial cortex: III. Cortical efferents.
AB  - We have investigated the cortical efferent projections of the macaque monkey
      retrosplenial and posterior cingulate cortices by using (3)H-amino acids as
      anterograde tracers. All the injections produced extensive local connections to
      other portions of this region. There were also a number of extrinsic efferent
      cortical connections, many of which have not hitherto been reported. Major
      projections from the retrosplenial cortex were directed to the frontal lobe, with
      heaviest terminations in areas 46, 9, 10, and 11. There were also very
      substantial projections to the entorhinal cortex, presubiculum, and parasubiculum
      of the hippocampal formation, as well as to areas TH and TF of the
      parahippocampal cortex. Some injections led to labeling of area V4, the dorsal
      bank of the superior temporal sulcus, and area 7a of the parietal cortex.
      Projections from the posterior cingulate cortex innervated all these same
      regions, although the density of termination was different from the retrosplenial
      projections. The posterior cingulate cortex gave rise to additional projections
      to parietal area DP and to the cortex along the convexity of the superior
      temporal gyrus. The ventral portion of the posterior cingulate cortex (area 23v)
      gave rise to much denser efferent projections to the hippocampal formation than
      the dorsal portions (areas 23e and i). These connections are discussed in
      relation to the clinical syndromes of retrosplenial amnesia and topographic
      disorientation in humans commonly caused by lesions in the caudoventral portions
      of the retrosplenial and posterior cingulate cortices.

PMID- 17436283
TI  - Deciphering the somite segmentation clock: beyond mutants and morphants.
AB  - The regular pattern of somite segmentation depends on a clock, the somite
      segmentation clock, in the form of a gene expression oscillator, operating in the
      presomitic mesoderm (the PSM) at the tail end of the vertebrate embryo. Genetic
      screens and other approaches have identified a variety of genes, including
      components and targets of the Notch signalling pathway, that show transcriptional
      oscillations in this region and appear to be necessary for correct segmentation.
      Mathematical modelling shows that the oscillations could plausibly be generated
      by a simple mechanism of delayed negative feedback, based on autoinhibition of
      Notch target genes of the Hes/her family by their own protein products. To move
      beyond plausible models to an experimentally validated theory, however, it is
      necessary to measure the parameters on which the proposed model is based and to
      devise ways of probing the dynamics of the system by means of timed disturbances
      so as to compare with the model's predictions. Some progress is being made in
      these directions.

PMID- 17436284
TI  - Xenopus hairy2 functions in neural crest formation by maintaining cells in a
      mitotic and undifferentiated state.
AB  - The neural crest is a population of mitotically active, multipotent progenitor
      cells that arise at the neural plate border. Neural crest progenitors must be
      maintained in a multipotent state until after neural tube closure. However, the
      molecular underpinnings of this process have yet to be fully elucidated. Here we
      show that the basic helix-loop-helix (bHLH) transcriptional repressor gene,
      Xenopus hairy2 (Xhairy2), is an essential early regulator of neural crest
      formation in Xenopus. During gastrulation, Xhairy2 is localized at the
      presumptive neural crest prior to the expression of such neural crest markers as
      Slug and FoxD3. Morpholino-mediated knockdown of Xhairy2 results in the
      repression of neural crest marker gene expression while inducing the ectopic
      expression of the cell cycle inhibitor p27(xic1) in the presumptive neural crest.
      We also found that ectopic p27(xic1) disturbs neural crest formation.
      Furthermore, the depletion of Xhairy2 leads to the apoptosis of mitotic cells.
      Our results suggest that Xhairy2 functions in neural crest specification by
      maintaining cells in the mitotic and undifferentiated state.

PMID- 17436285
TI  - Temporal and spatial regulation of alpha6 integrin expression during the
      development of the cochlear-vestibular ganglion.
AB  - The neurons of the cochlear-vestibular ganglion (CVG) that innervate the sensory
      hair cells of the inner ear are derived from the otic epithelium early in
      development. Neuroblasts detach from neighboring cells, migrate into the
      mesenchyme where they coalesce to form the ganglion complex, then send processes
      back into the epithelium. Cell migration and neuronal process formation involve
      changes in cellular interactions with other cells and proteins in the
      extracellular matrix that are orchestrated by cell surface-expressed adhesion
      molecules, including the integrins. I studied the expression pattern of the
      alpha6 integrin subunit during the early development of the CVG using
      immunohistochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR)
      in murine tissue sections, otocyst, and ganglion explants. At embryonic day
      (E)10.5 alpha6 integrin was expressed in the otic epithelium but not in migrating
      neuroblasts. Importantly, the loss of alpha6 was associated with exit from the
      epithelium, not neuronal determination, revealing differentiation cues acutely
      associated with the cellular environment. Markers of glial and neuronal phenotype
      showed that alpha6-expressing cells present in the CVG at this stage were glia of
      neural crest origin. By E12.5 alpha6 expression in the ganglion increased
      alongside the elaboration of neuronal processes. Immunohistochemistry applied to
      otocyst cultures in the absence of glia revealed that neuronal processes remained
      alpha6-negative at this developmental stage and confirmed that alpha6 was
      expressed by closely apposed glia. The spatiotemporal modulation of alpha6
      expression suggests changing roles for this integrin during the early development
      of inner ear innervation.

PMID- 17436286
TI  - Anatomy of the posterior caudal lobe of the cerebellum and the eminentia
      granularis posterior in a mormyrid fish.
AB  - The cerebellum of mormyrid fish is of interest for its large size and unusual
      histology. The mormyrid cerebellum, as in all ray-finned fishes, has three
      subdivisions--valvula, corpus, and caudal lobe. The structures of the mormyrid
      valvula and corpus have been examined previously, but the structure of the
      mormyrid caudal lobe has not been studied. The mormyrid caudal lobe includes a
      posterior caudal lobe associated with the electrosense and an anterior caudal
      lobe associated with lateral line and eighth nerve senses. In this article we
      describe cellular elements of the posterior caudal lobe and of the eminentia
      granularis posterior (EGp) in the mormyrid fish Gnathonemus petersii. The EGp
      gives rise to the parallel fibers of the posterior caudal lobe. We used
      intracellular injection of biocytin, extracellular injection of biotinylated
      dextran amine, and immunohistochemistry with antibodies to gamma-aminobutyric
      acid, inositol triphosphate receptor I, calretinin, and Zebrin II. The
      histological structure of the posterior caudal lobe is markedly irregular in
      comparison to that of the corpus and the valvula, and a tight modular
      organization of cerebellar elements is less apparent here. Most Purkinje cell
      bodies are in the middle of the molecular region. Their dendrites are only
      roughly oriented in the sagittal plane, extend both ventrally and dorsally, and
      branch irregularly. Climbing fibers terminate only on smooth dendrites near the
      soma. Most Purkinje cell axons terminate locally on eurydendroid cells that
      project outside the cortex. The results provide an additional variant to the
      already large set of different cerebellar and cerebellum-like structures.

PMID- 17436287
TI  - Endomorphin-2-immunoreactive fibers selectively appose serotonergic neuronal
      somata in the rostral ventral medial medulla.
AB  - The rostral portion of the ventral medial medulla (RVM) is a crucial site for the
      supraspinal antinociceptive actions of opioids. Previous studies have reported
      that serotonergic antagonists block the analgesia induced by microinjection of
      morphine into the RVM (Hammond and Yaksh [1984] Brain Res 298:329-337) and that
      spinally projecting serotonergic RVM neurons express mu-opioid receptors (MOR)
      (Kalyuzhny et al. [1996] J Neurosci 16:6490-6503; Wang and Wessendorf [1999] J
      Comp Neurol 404:183-196). In addition, axons immunoreactive for the endogenous
      MOR ligand endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) (EM-2) have been reported to be in
      the RVM (Martin-Schild et al. [1999] J Comp Neurol 405:450-471; Pierce and
      Wessendorf [2000] J Chem Neuroanat 18:181-207). In the present study we examined
      the relationship of EM-2-immunoreactive (EM-2-ir) axons to serotonergic and
      nonserotonergic RVM neurons in rats, including neurons projecting to the dorsal
      spinal cord. We also examined the origins of EM-2-ir in the RVM. Using unbiased
      methods we estimated the total number of cells in the RVM to be 1.50 x 10(4) and
      of these up to 70% were retrogradely labeled from the dorsal spinal cord. EM-2-ir
      fibers apposed both serotonergic and nonserotonergic RVM neuronal profiles.
      However, serotonergic profiles were significantly more likely to be apposed than
      nonserotonergic profiles. Thus, although serotonergic neurons comprise a minority
      of RVM neurons (23% of the total RVM neurons), they appear to be selectively
      apposed by EM-2-ir fibers. We also found that hypothalamic EM-2-ir neurons, but
      not EM-2-ir neurons, in the nucleus of the solitary tract projected their axons
      to the RVM.

PMID- 17436288
TI  - Architecture of the primary taste center of Drosophila melanogaster larvae.
AB  - A simple nervous system combined with stereotypic behavioral responses to
      tastants, together with powerful genetic and molecular tools, have turned
      Drosophila larvae into a very promising model for studying gustatory coding.
      Using the Gal4/UAS system and confocal microscopy for visualizing gustatory
      afferents, we provide a description of the primary taste center in the larval
      central nervous system. Essentially, gustatory receptor neurons target different
      areas of the subesophageal ganglion (SOG), depending on their segmental and
      sensory organ origin. We define two major and two smaller subregions in the SOG.
      One of the major areas is a target of pharyngeal sensilla, the other one receives
      inputs from both internal and external sensilla. In addition to such spatial
      organization of the taste center, circumstantial evidence suggests a subtle
      functional organization: aversive and attractive stimuli might be processed in
      the anterior and posterior part of the SOG, respectively. Our results also
      suggest less coexpression of gustatory receptors than proposed in prior studies.
      Finally, projections of putative second-order taste neurons seem to cover large
      areas of the SOG. These neurons may thus receive multiple gustatory inputs. This
      suggests broad sensitivity of secondary taste neurons, reminiscent of the
      situation in mammals.

PMID- 17436289
TI  - Progranulin null mutations in both sporadic and familial frontotemporal dementia.
AB  - Frontotemporal dementia (FTD) is the second most frequent type of
      neurodegenerative dementias. Mutations in the progranulin gene (GRN, PGRN) were
      recently identified in FTDU-17, an FTD subtype characterized by ubiquitin
      immunoreactive inclusions and linkage to chromosome 17q21. We looked for PGRN
      mutations in a large series of 210 FTD patients (52 familial, 158 sporadic) to
      accurately evaluate the frequency of PGRN mutations in both sporadic and familial
      FTD, and FTD with associated motoneuron disease (FTD-MND), as well as to study
      the clinical phenotype of patients with a PGRN mutation. We identified nine novel
      PGRN null mutations in 10 index patients. The relative frequency of PGRN null
      mutations in FTD was 4.8% (10/210) and 12.8% (5/39) in pure familial forms.
      Interestingly, 5/158 (3.2%) apparently sporadic FTD patients carried a PGRN
      mutation, suggesting the possibility of de novo mutations or incomplete
      penetrance. In contrast, none of the 43 patients with FTD-MND had PGRN mutations,
      supporting that FTDU-17 and FTD-MND are genetically distinct. The clinical
      phenotype of PGRN mutation carriers was particular because of the wide range in
      onset age and the frequent occurrence of early apraxia (50%), visual
      hallucinations (30%), and parkinsonism (30%) during the course of the disease.
      This study supports that PGRN null mutations represent a more frequent cause of
      FTD than MAPT mutations (4.8% vs. 2.9%) but are not responsible for FTD-MND. It
      also demonstrates that half of the patients with a PGRN mutation in our series
      had no apparent family history of dementia. Taking this into account, genetic
      testing should be now considered more systematically, even in patients without
      obvious familial history of FTD.

PMID- 17436290
TI  - Age-related accumulation of Marinesco bodies and lipofuscin in rhesus monkey
      midbrain dopamine neurons: relevance to selective neuronal vulnerability.
AB  - Parkinson's disease (PD) is characterized by degeneration of nigrostriatal
      dopamine (DA) neurons. Although aging is a primary risk factor for PD, its role
      in DA neuron degeneration remains unknown. Neurodegeneration in PD is not uniform
      throughout the ventral midbrain: the ventral tier of the substantia nigra (vtSN)
      is most vulnerable, whereas the dorsal tier (dtSN) and ventral tegmental area
      (VTA) are relatively resistant. We studied young (9-10 years old), middle-aged
      (14-17 years old), and old-aged (22-29 years old) rhesus monkeys to identify
      factors potentially underlying selective vulnerability and their association with
      aging. We focused on markers relevant to the ubiquitin-proteasome (UPS) and
      lysosome systems. Unbiased stereological counting was performed on tyrosine
      hydroxylase-positive (TH+) neurons and TH+ neurons containing Marinesco bodies
      (TH+MB) or lipofuscin (TH+lipo), markers of UPS or lysosomal activity,
      respectively. TH+ neuron numbers were inversely correlated with advancing age
      specifically in the vtSN, not the dtSN or VTA. TH intensity decreased throughout
      the ventral midbrain with increasing age, an effect exacerbated in the vtSN.
      TH+MB neurons were localized in the vulnerable vtSN of old monkeys. The number of
      MBs per cell increased with age, and TH intensity of TH+MB neurons decreased in
      middle age. Conversely, TH+lipo neurons were primarily found in the resistant
      dtSN and VTA. These data suggest that particular age-related changes localize to
      DAergic subregions relevant to degenerative patterns in PD. Furthermore, the
      results begin to characterize the nature of the link between aging and PD, and
      they support the concept that aged monkeys represent a valuable model for
      studying specific events preceding PD.

PMID- 17436291
TI  - Evolution of neuronal patterning in free-living rhabditid nematodes I: Sex
      specific serotonin-containing neurons.
AB  - As a first step toward understanding the evolution of neuronal patterning and
      function in a group of simple animals, we have examined serotonin-containing
      neurons in 17 species of free-living rhabditid nematodes and compared them with
      identified neurons of Caenorhabditis elegans. We found many serotonin
      immunoreactive (serotonin-IR) neurons that are likely homologs of those in C.
      elegans; this paper focuses on sex-specific neurons such as the egg laying
      hermaphrodite-specific neurons (HSNs), VCs, and male CAs, CPs, and ray sensory
      neurons known to function in mating. These cells vary in number and position in
      the species examined but are consistent with a current molecularly based
      phylogeny. Two groups (Oscheius and Pristionchus) appear independently to have
      lost a serotonin-IR HSN. Oscheius furthermore has no serotonin-IR innervation of
      the vulval region, in contrast to every other species we examined. We also saw
      variation in the location of somas of putative HSN, consistent with evolutionary
      changes in HSN migration. In C. elegans, the HSN soma migrates during
      embryogenesis from the tail to the central body, where it innervates its major
      postsynaptic targets, the vulval muscles. For other species, we observed putative
      HSN homologs along the anterior-posterior axis from the head to the tail, but
      typically HSNs were located near the vulva, which also varies in anterior
      posterior position among the species we examined. The varying positions of the
      HSN somas in other species are reminiscent of phenotypes seen in various C.
      elegans mutants with altered HSN migration, suggesting possible mechanisms for
      the evolutionary differences we observed.

PMID- 17436292
TI  - Rapid and preferential activation of Fos protein in hypocretin/orexin neurons
      following the reversal of dehydration-anorexia.
AB  - Dehydration (DE)-anorexia is stimulated by chronic consumption of hypertonic
      saline. Spontaneous nocturnal food intake is markedly reduced with this treatment
      but is rapidly reversed upon the return of drinking water. Here we examined the
      neurons in the lateral hypothalamic area (LHA) of chronically dehydrated rats for
      their peptidergic phenotype, colocalization, and activation profiles following
      the rapid reversal of anorexia. To do this, we used double-labeling combinations
      of Fos immunocytochemistry and radioisotopic- and digoxigenin-labeled in situ
      hybridization. We found that lateral hypothalamic corticotropin-releasing hormone
      (CRH) neurons show extensive coexpression with neurotensin mRNA, but they are
      distinct from hypocretin/orexin and melanin-concentrating hormone (MCH) neurons.
      Chronic dehydration increases Fos-ir in large numbers of neurons in dorsal
      regions of the LHA. Some of these LHA neurons also show increased CRH, but not
      hypocretin/orexin or MCH gene expression, as dehydration-anorexia develops.
      Furthermore, the behavioral sequence of eating and increased activity exhibited
      by DE animals in the minutes following water drinking is accompanied by a further
      increase in the number of Fos-ir nuclei in the LHA. Increased Fos activation
      occurs in a significant number of LHA hypocretin/orexin neurons, but not CRH or
      MCH neurons, in the LHA. Together these data implicate CRH but not
      hypocretin/orexin or MCH neurons in the LHA in the motor events associated with
      dehydration. However, when water is returned, contributions to the network
      controlling responses evidently come from hypocretin/orexin, but not CRH or MCH,
      neurons in the LHA.

PMID- 17436293
TI  - Genetic dissection of neural circuit anatomy underlying feeding behavior in
      Drosophila: distinct classes of hugin-expressing neurons.
AB  - The hugin gene of Drosophila encodes a neuropeptide with homology to mammalian
      neuromedin U. The hugin-expressing neurons are localized exclusively to the
      subesophageal ganglion of the central nervous system and modulate feeding
      behavior in response to nutrient signals. These neurons send neurites to the
      protocerebrum, the ventral nerve cord, the ring gland, and the pharynx and may
      interact with the gustatory sense organs. In this study, we have investigated the
      morphology of the hugin neurons at a single-cell level by using clonal analysis.
      We show that single cells project to only one of the four major targets. In
      addition, the neurites of the different hugin cells overlap in a specific brain
      region lateral to the foramen of the esophagus, which could be a new site of
      neuropeptide release for feeding regulation. Our study reveals novel complexity
      in the morphology of individual hugin neurons, which has functional implication
      for how they coordinate feeding behavior and growth.

PMID- 17436294
TI  - Phospholipase Cbeta4 expression reveals the continuity of cerebellar topography
      through development.
AB  - Mediolateral boundaries divide the mouse cerebellar cortex into four transverse
      zones, and within each zone the cortex is further subdivided into a symmetrical
      array of parasagittal stripes. Various expression markers reveal this complexity,
      and detailed maps have been constructed based on the differential expression of
      zebrin II/aldolase C in a Purkinje cell subset. Recently, phospholipase (PL)
      Cbeta4 expression in adult mice was shown to be restricted to, and coextensive
      with, the zebrin II-immunonegative Purkinje cell subset. The Purkinje cell
      expression of PLCbeta4 during embryogenesis and postnatal development begins just
      before birth in a subset of Purkinje cells that are clustered to form a
      reproducible array of parasagittal stripes. Double label and serial section
      immunocytochemistry revealed that the early PLCbeta4-immunoreactive clusters in
      the neonate are complementary to those previously identified by neurogranin
      expression. The PLCbeta4 expression pattern can be traced continuously from
      embryo to adult, revealing the continuity of the topographical map from perinatal
      to adult cerebella. The only exception, as has been seen for other antigenic
      markers, is that transient PLCbeta4 expression (which subsequently disappears) is
      seen in some Purkinje cell stripes during the second postnatal week. Furthermore,
      the data confirm that some adult Purkinje cell stripes are composite in origin,
      being derived from two or more distinct embryonic clusters. Thus, the zone and
      stripe topography of the cerebellum is conserved from embryo to adult, confirming
      that the early- and late-antigenic markers share a common cerebellar topography.

PMID- 17436295
TI  - Congenital diaphragmatic hernia (CDH) etiology as revealed by pathway genetics.
AB  - Congenital diaphragmatic hernia (CDH) is a common birth defect with high
      mortality and morbidity. Two hundred seventy CDH patients were ascertained,
      carefully phenotyped, and classified as isolated (diaphragm defects alone) or
      complex (with additional anomalies) cases. We established different strategies to
      reveal CDH-critical chromosome loci and genes in humans. Candidate genes for
      sequencing analyses were selected from CDH animal models, genetic intervals of
      recurrent chromosomal aberration in humans, such as 15q26.1-q26.2 or 1q41-q42.12,
      as well as genes in the retinoic acid and related pathways and those known to be
      involved in embryonic lung development. For instance, FOG2, GATA4, and COUP-TFII
      are all needed for both normal diaphragm and lung development and are likely all
      in the same genetic and molecular pathway. Linkage analysis was applied first in
      a large inbred family and then in four multiplex families with Donnai-Barrow
      syndrome (DBS) associated with CDH. 10K SNP chip and microsatellite markers
      revealed a DBS locus on chromosome 2q23.3-q31.1. We applied array-based
      comparative genomic hybridization (aCGH) techniques to over 30, mostly complex,
      CDH patients and found a de novo microdeletion in a patient with Fryns syndrome
      related to CDH. Fluorescence in situ hybridization (FISH) and multiplex ligation
      dependent probe amplification (MLPA) techniques allowed us to further define the
      deletion interval. Our aim is to identify genetic intervals and, in those, to
      prioritize genes that might reveal molecular pathways, mutations in any step of
      which, might contribute to the same phenotype. More important, the elucidation of
      pathways may ultimately provide clues to treatment strategies.

PMID- 17436296
TI  - Development of the diaphragm and genetic mouse models of diaphragmatic defects.
AB  - Improving our understanding of diaphragmatic development is essential to making
      progress in defining the pathogenesis and genetic etiologies of congenital
      diaphragmatic defects in humans. As mouse genetic technology has given us new
      tools to manipulate and observe development, a number of mouse models have
      recently emerged that provide valuable insight to this field. In this article, we
      review our current understanding of diaphragmatic embryogenesis including the
      origin of diaphragmatic tissue. We use rodent models to review the
      muscularization of the diaphragm and review selected genetic models of abnormal
      muscularization. We also review models of posterior diaphragmatic defects and
      discuss evidence for the pleuroperitoneal fold (PPF) tissue contributing to the
      diaphragm. Finally, we discuss models of anterior and central hernias. It may be
      simplistic to subdivide this review based on anatomic regions of the diaphragm,
      as evidence is emerging that defects in different regions of the diaphragm in
      humans and in mice may be etiologically related. However, at this time we do not
      have enough knowledge to make more mechanistic or genetic classifications though
      with time, genetic progress in the field of diaphragm development will allow us
      to do this.

PMID- 17436297
TI  - Tracheal occlusion: a review of obstructing fetal lungs to make them grow and
      mature.
AB  - Fetal lung growth and functional differentiation are affected strongly by the
      extent that pulmonary tissue is distended (expanded) by liquid that naturally
      fills developing future airspaces. Methods that prevent normal egress of this
      lung fluid through the trachea magnify mechanical stretching of lung parenchymal
      cells, thereby promoting lung development. Indeed, experimental observations
      demonstrate that in utero tracheal occlusion (TO) performed on fetuses during the
      late canalicular-early saccular stage potently stimulates pulmonary growth and
      maturation. In this review, we present the four principle non-human animal models
      of TO/obstruction and discuss them in relation to their utility in elucidating
      lung development, in remedying congenital diaphragmatic hernia (CDH) as well as
      in investigating the stretching effects on growth and remodeling of the fine
      vasculature.

PMID- 17436299
TI  - Localization of corticotropin-releasing factor, urotensin I, and CRF-binding
      protein gene expression in the brain of the zebrafish, Danio rerio.
AB  - Our current understanding of the corticotropin-releasing factor (CRF) system
      distribution in the teleost brain is restricted by limited immunohistochemical
      studies and a lack of complete transcriptional distribution maps. The present
      study used in situ hybridization to localize and compare CRF, urotensin I (UI),
      and CRF-binding protein (CRF-BP) expression in the brain of adult zebrafish
      (Danio rerio). All three peptides were localized in the preoptic area,
      periventricular hypothalamic and tectal regions, and dorsal part of the
      trigeminal motor nucleus. CRF and UI were both expressed in several nuclei of the
      dorsal telencephalon, whereas CRF and CRF-BP were both expressed in the ventral
      nucleus of the ventral telencephalon. Sole expression of CRF and CRF-BP was
      apparent in the olfactory bulbs and superior raphe nucleus, respectively, whereas
      only UI was observed in the corpus mamillare, nucleus of the medial longitudinal
      fascicle, dorsal tegmental nucleus, nucleus lateralis valvulae, and nucleus
      interpeduncularis. A major finding of this study was the general regional
      overlapping of CRF-BP with its ligands and a tendency to be expressed in tandem
      with CRF rather than UI. Overall, the mRNA expression patterns outlined in this
      study support the stress-related neuroendocrine, autonomic, and behavioral
      functions generally ascribed to the vertebrate CRF system and suggest some unique
      functional roles for CRF and UI in the teleost brain.

PMID- 17436298
TI  - Overview of epidemiology, genetics, birth defects, and chromosome abnormalities
      associated with CDH.
AB  - Congenital diaphragmatic hernia (CDH) is a common and well-studied birth defect.
      The etiology of most cases remains unknown but increasing evidence points to
      genetic causation. The data supporting genetic etiologies which are detailed
      below include the association of CDH with recurring chromosome abnormalities, the
      existence of CDH-multiplex families, and the co-occurrence of CDH with additional
      congenital malformations.

PMID- 17436300
TI  - Single gene disorders associated with congenital diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) is a common birth defect with a high pre-
      and postnatal mortality. Although the majority of diaphragmatic hernias occur as
      isolated malformations, additional major and minor anomalies are common and are
      present in more than 40% of patients. There are compelling data for the
      importance of genetic factors in the etiology of CDH, but the pathogenesis and
      the causative genes for CDH in humans remain elusive. There are more than 70
      syndromes in which diaphragmatic hernias have been described, and several of
      these syndromes are single gene disorders for which the gene is known. One method
      for identifying the causative genes in isolated CDH is to study syndromes with
      known genes in which CDH is a recognized feature, with the rationale that those
      genes have a role in diaphragm development. This review discusses the syndromes
      that are most commonly associated with CDH, with greater attention towards
      syndromes in which the causative genes have been identified, including Simpson
      Golabi-Behmel syndrome, Denys-Drash syndrome, spondylocostal dysostosis,
      craniofrontonasal syndrome, Cornelia de Lange syndrome and Marfan syndrome.

PMID- 17436301
TI  - Congenital diaphragmatic hernia and associated cardiovascular malformations:
      type, frequency, and impact on management.
AB  - The co-occurrence of congenital diaphragmatic hernia (CDH) and cardiovascular
      malformations (CVMs) has important clinical, genetic, and developmental
      implications. Previous examinations of this topic often included patients with
      genetic syndromes. To correct this potential bias, we undertook an extensive
      review of the literature and obtained new data. The frequency of CVMs associated
      with isolated CDH was 11-15%. A careful analysis of CVMs indicates that atrial
      and ventricular septal defects, conotruncal defects, and left ventricular outflow
      tract obstructive defects were the most common type of CVMs, but proportional to
      the frequency of occurrence in the general population. The combination of CVM and
      CDH results in a poorer prognosis than would be expected with either malformation
      alone. However, the impact on survival from patients with a genetic syndrome has
      not been consistently evaluated. We encourage researchers to re-analyze existing
      series and recommend that future studies distinguish isolated CDH from that which
      is associated with other malformations, especially as part of genetic syndromes.
      Therapies should be tailored to maximize cardiac output and systemic oxygen
      delivery rather than systemic oxygen saturation alone. Although there is
      speculation about the frequency with which isolated left ventricular "hypoplasia"
      occurs in patients with CDH, we suggest it results from compression of a pre-load
      deficient left ventricle by the hypertensive right ventricle, and unlike true
      hypoplasia, is reversible. Irrespective of the type of severity of CVMs in
      patients with CDH, the degree of pulmonary hypoplasia and pulmonary vascular
      disease predicts outcome.

PMID- 17436302
TI  - Peptide products of the afp-6 gene of the nematode Ascaris suum have different
      biological actions.
AB  - Matrix-assisted laser desorption/ionization time-of-flight and tandem time-of
      flight (MALDI-TOF and MALDI-TOF/TOF) mass spectrometry were used to sequence and
      localize three novel, related neuropeptides in the nervous system of the nematode
      Ascaris suum, AMRNALVRFamide (AF21), NGAPQPFVRFamide (AF22), and SGMRNALVRFamide
      (AF23). The amino acid sequences were used to clone a novel neuropeptide gene
      (afp-6) that encodes a precursor bearing a single copy of each of the peptides.
      In situ hybridization and immunocytochemistry revealed that both the transcript
      and the peptides are expressed in a single cell in the ventral ganglion.
      Pharmacological studies of intact nematodes injected with these peptides, as well
      as physiological studies of responses to them in muscle tissue, motor neurons,
      and the pharynx, reveal that these peptides have potent bioactivity in the
      locomotory and feeding systems. Further exploration of their effects may
      contribute to our understanding of neuropeptide modulation of behavior and also
      to the development of compounds with anthelmintic relevance.

PMID- 17436303
TI  - Lung development and implications for hypoplasia found in congenital
      diaphragmatic hernia.
AB  - Congenital diaphragmatic hernia (CDH) is associated with various degrees of
      pulmonary hypoplasia and severe persistent pulmonary hypertension in the newborn.
      These conditions have significant implications for the outcome for the patient.
      Defects in early lung development are likely to be central to the generation of
      hypoplasia. A number of mouse models with defects in pathways that are central to
      lung development were found to have CDH. Understanding all aspects of early lung
      development will provide fresh insight into the pathogenesis of CDH and its
      associated conditions.

PMID- 17436304
TI  - Antenatal and postnatal lung and vascular anatomic and functional studies in
      congenital diaphragmatic hernia: implications for clinical management.
AB  - Congenital diaphragmatic hernia is characterized by fetal and neonatal lung
      hypoplasia as well as vascular hypoplasia. Antenatal imaging studies have been
      performed that attempt to quantify the degree of hypoplasia and its impact on
      infant prognosis. Prenatal and perinatal growth of the lung and vasculature are
      interdependent and their continued coordinated growth is critical for survival
      after birth in this patient population. Lung protection strategies appear to
      improve survival in newborns with diaphragmatic hernia, but a subset of infants
      remain who demonstrate sufficiently severe lung hypoplasia that we are unable to
      provide support long-term after birth. Fetal intervention is a strategy designed
      to enhance fetal lung growth towards improving survival in this most severely
      affected group, though other therapies to enhance postnatal lung and vascular
      growth should be concurrently investigated. However, any of these interventions
      will require careful selection of those infants at risk for poor outcome and
      thorough follow up, since long-term morbidity is significant in children with
      diaphragmatic hernia.

PMID- 17436305
TI  - Vitamin A deficiency (VAD), teratogenic, and surgical models of congenital
      diaphragmatic hernia (CDH).
AB  - Congenital diaphragmatic hernia (CDH) is a congenital malformation that occurs
      with a frequency of 0.08 to 0.45 per 1,000 births. Children with CDH are born
      with the abdominal contents herniated through the diaphragm and exhibit an
      associated pulmonary hypoplasia which is frequently accompanied by severe
      morbidity and mortality. Although the etiology of CDH is largely unknown,
      considerable progress has been made in understanding its molecular mechanisms
      through the usage of genetic, teratogenic, and surgical models. The following
      review focuses on the teratogenic and surgical models of CDH and the possible
      molecular mechanisms of nitrofen (a diphenyl ether, formerly used as an
      herbicide) in both induction of CDH and pulmonary hypoplasia. In addition, the
      mechanisms of other compounds including several anti-inflammatory agents that
      have been linked to CDH will be discussed. Furthermore, this review will also
      explore the importance of vitamin A in lung and diaphragm development and the
      possible mechanisms of teratogen interference in vitamin A homeostasis. Continued
      exploration of these models will bring forth a clearer understanding of CDH and
      its molecular underpinnings, which will ultimately facilitate development of
      therapeutic strategies.

PMID- 17436306
TI  - Congenital diaphragmatic hernia and pulmonary hypoplasia: new insights from
      developmental biology and genetics.

PMID- 17436307
TI  - An application of the patient rule-induction method for evaluating the
      contribution of the Apolipoprotein E and Lipoprotein Lipase genes to predicting
      ischemic heart disease.
AB  - Different combinations of genetic and environmental risk factors are known to
      contribute to the complex etiology of ischemic heart disease (IHD) in different
      subsets of individuals. We employed the Patient Rule-Induction Method (PRIM) to
      select the combination of risk factors and risk factor values that identified
      each of 16 mutually exclusive partitions of individuals having significantly
      different levels of risk of IHD. PRIM balances two competing objectives: (1)
      finding partitions where the risk of IHD is high and (2) maximizing the number of
      IHD cases explained by the partitions. A sequential PRIM analysis was applied to
      data on the incidence of IHD collected over 8 years for a sample of 5,455
      unrelated individuals from the Copenhagen City Heart Study (CCHS) to assess the
      added value of variation in two candidate susceptibility genes beyond the
      traditional, lipid and body mass index risk factors for IHD. An independent
      sample of 362 unrelated individuals also from the city of Copenhagen was used to
      test the model obtained for each of the hypothesized partitions.

PMID- 17436308
TI  - Testing association in the presence of linkage--a powerful score for binary
      traits.
AB  - We present a score for testing association in the presence of linkage for binary
      traits. The score is robust to varying degrees of linkage, and it is valid under
      any ascertainment scheme based on trait values as well as under population
      stratification. The score test is derived from a mixed effects model where
      population level association is modeled using a fixed effect and where
      correlation among related individuals is allowed for by using log-gamma random
      effects. The score, as presented in this paper, does not assume full information
      about the inheritance pattern in families or parental genotypes. We compare the
      score to the semi-parametric family-based association test (FBAT), which has won
      ground because of its flexible and simple form. We show that a random effects
      formulation of co-inheritance can improve the power substantially. We apply the
      method to data from the Collaborative Study on the Genetics of Alcoholism. We
      compare our findings to previously published results.

PMID- 17436309
TI  - Identification of the neurotransmitters involved in modulation of transmitter
      release from the central terminals of the locust wing hinge stretch receptor.
AB  - The flight motor system of the locust represents a model preparation for the
      investigation of neuromodulation. At the wing hinges are stretch receptors
      important in generating and controlling the flight motor pattern. The forewing
      stretch receptor (fSR) makes direct cholinergic synapses with depressor motor
      neurons (MN) controlling that wing, including the first basalar MN (BA1). The
      fSR/BA1 synapse is modulated by muscarinic cholinergic receptors located on gamma
      aminobutyric acid (GABA)-ergic interneurons (Judge and Leitch [1999a] J. Comp.
      Neurol. 407:103-114; Judge and Leitch [1999b] J. Neurobiol. 40:420-431). However,
      electrophysiology has shown that fSR/BA is also modulated by biogenic amines
      (Leitch et al. [2003] J. Comp. Neurol. 462:55-70). We have used electron
      microscopic immunocytochemistry (ICC) to identify the neurotransmitters in
      neurons presynaptic to the fSR and to determine the relative proportion of these
      different classes of modulatory inputs. Approximately 55% of all inputs to the
      fSR are glutamate-IR, indicating that glutamatergic neurons may also play an
      important role in presynaptically modulating the fSR terminals. Anti-GABA ICC
      confirmed that over 40% of inputs to the fSR are GABA-IR (Judge and Leitch
      [1999a] J. Comp. Neurol. 407:103-114). Labelling sections with an antioctopamine
      antibody revealed neurons containing distinctive large, electron-dense granules,
      which could reliably be used to identify them. Aminergic neurons that modulate
      the synapse may have very few morphologically recognizable synaptic outputs.
      Although putative octopaminergic processes were found in close contact to
      horseradish peroxidase-filled fSR profiles, no morphologically recognizable
      synaptic inputs to the fSR were evident. Collectively, these data suggest that
      most inputs to the fSR are from either glutamatergic or GABAergic neurons.

PMID- 17436310
TI  - Accelerated failure time models with covariates subject to measurement error.
AB  - It has been well known that ignoring measurement error may result in
      substantially biased estimates in many contexts including linear and nonlinear
      regressions. For survival data with measurement error in covariates there has
      been extensive discussion in the literature with the focus being on the Cox
      proportional hazards models. However, the impact of measurement error on
      accelerated failure time (AFT) models has received little attention, though AFT
      models are very useful in survival data analysis. In this paper, we discuss AFT
      models with error-prone covariates and study the bias induced by the naive
      approach of ignoring measurement error in covariates. To adjust for such a bias,
      we describe a simulation and extrapolation method. This method is appealing
      because it is simple to implement and it does not require modelling the true but
      error-prone covariate process that is often not observable. Asymptotic normality
      for the resulting estimators is established. Simulation studies are carried out
      to evaluate the performance of the proposed method as well as the impact of
      ignoring measurement error in covariates. The proposed method is applied to
      analyse a data set arising from the Busselton Health study (Australian J. Public
      Health 1994; 18:129-135).

PMID- 17436311
TI  - Large-scale population-based metabolic phenotyping of thirteen genetic
      polymorphisms related to one-carbon metabolism.
AB  - Several polymorphisms of genes involved in one-carbon metabolism have been
      identified. The reported metabolic phenotypes are often based on small studies
      providing inconsistent results. This large-scale study of 10,601 population-based
      samples was carried out to investigate the association between a panel of
      biochemical parameters and genetics variants related to one-carbon metabolism.
      Concentrations of total homocysteine (tHcy), folate, vitamin B(12) (cobalamin),
      methylmalonic acid (MMA), vitamin B(2) (riboflavin), vitamin B(6) (PLP), choline,
      betaine, dimethylglycine (DMG), cystathionine, cysteine, methionine, and
      creatinine were determined in serum/plasma. All subjects were genotyped for 13
      common polymorphisms: methylenetetrahydrofolate reductase (MTHFR) c.665C>T (known
      as 677C>T; p.Ala222Val) and c.1286A>C (known as 1298A>C; p.Glu429Ala); methionine
      synthase (MTR) c.2756A>G (p.Asp919Gly); methionine synthase reductase (MTRR)
      c.66A>G (p.Ile22Met); methylenetetrahydrofolate dehydrogenase (MTHFD1) c.1958G>A
      (p.Arg653Gln); betaine homocysteine methyltransferase (BHMT) c.716G>A (known as
      742G>A; p.Arg239Gln); cystathionine beta-synthase (CBS) c.844_845ins68 and
      c.699C>T (p.Tyr233Tyr); transcobalamin-II (TCN2) c.67A>G (p.Ile23Val) and
      c.776C>G (p.Pro259Arg); reduced folate carrier-1 (SLC19A1) c.80G>A (p.Arg27His);
      and paraoxonase-1 (PON1) c.163T>A (p.Leu55Met) and c.575A>G (p.Gln192Arg). The
      metabolic profile in terms of the measured vitamins and metabolites were
      investigated for these 13 polymorphisms. We confirmed the strong associations of
      MTHFR c.665C>T with tHcy and folate, but also observed significant (P<0.01)
      changes in metabolite concentrations according to other gene polymorphisms. These
      include MTHFR c.1286A>C (associations with tHcy, folate and betaine), MTR
      c.2756A>G (tHcy), BHMT c.716G>A (DMG), CBS c.844_845ins68 (tHcy, betaine), CBS
      c.699C>T (tHcy, betaine, cystathionine) and TCN2 c.776C>G (MMA). No associations
      were observed for the other polymorphisms investigated.

PMID- 17436312
TI  - Gender differences in obsessive-compulsive symptom dimensions.
AB  - The aim of our study was to assess the role of gender in OCD symptom dimensions
      with a multivariate analysis while controlling for history of tic disorders and
      age at onset of OCD. One hundred and eighty-six consecutive outpatients with a
      DSM-IV diagnosis of OCD were interviewed. Yale-Brown Obsessive-Compulsive Scale
      (YBOC-S), YBOC-S Symptom Checklist, and Hamilton Depression and Anxiety Scales
      were administered to all patients. Lifetime history of tic disorders was assessed
      with the tic inventory section of the Yale Global Tic Severity Scale. Age at
      onset of OCD was assessed by direct interview. Statistical analysis was carried
      out through logistic regression to calculate adjusted female:male odds ratios
      (OR) for each dimension. A relationship was found between gender and two main OCD
      dimensions: contamination/cleaning (higher in females; female:male OR=2.02,
      P=0.03) and sexual/religious (lower in females; female:male OR=0.41, P=0.03). We
      did not find gender differences in the aggressive/checking, symmetry/ordering, or
      hoarding dimensions. We also found a greater history of tic disorders in those
      patients with symptoms from the symmetry/ordering, dimension (P<0.01). Both
      symmetry/ordering and sexual/religious dimensions were associated with an earlier
      age at onset of OCD (P<0.05). Gender is a variable that plays a role in the
      expression of OCD, particularly the contamination/cleaning and sexual/religious
      dimensions. Our results underscore the need to examine the relationship between
      OCD dimensions and clinical variables such as gender, tics, age at onset and
      severity of the disorder to improve the identification of OCD subtypes.

PMID- 17436313
TI  - Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia.
AB  - Heterozygous mutations of ELA2, encoding the protease neutrophil elastase (NE),
      cause either autosomal dominant cyclic neutropenia or severe congenital
      neutropenia (SCN). Three hypotheses have been proposed for how allelic mutations
      produce these different disorders: 1) disruption of proteolytic activity; 2)
      mislocalization of the protein; or 3) destabilization of the protein resulting in
      induction of the unfolded protein response. As with other dominant diseases with
      reduced reproductive fitness, sporadic cases can result from new mutations not
      inherited from either parent. Here we report an exceptional genetic phenomenon in
      which both a cyclic neutropenia patient and an SCN patient each possess two new
      ELA2 mutations. Because of the rarity of the phenomenon, we investigated the
      origins of the mutations and found that both arise nonmosaically and in cis from
      the paternally-inherited allele. Moreover, these cases offer a unique opportunity
      to investigate molecular pathways distinguishing these two forms of hereditary
      neutropenia. We have characterized the mutants separately and in combination,
      with respect to their effects on proteolysis, subcellular trafficking, and
      induction of the unfolded protein response. Each pair of mutations acts more or
      less additively to produce equivalent net effects on reducing proteolytic
      activity and induction of the unfolded protein response, yet each has different
      and somewhat opposing effects on disturbing subcellular localization, thus
      offering support for a role for protein mistrafficking as a disease mechanism.

PMID- 17436314
TI  - Periarticular ligament changes following ACL/MCL transection in an ovine stifle
      joint model of osteoarthritis.
AB  - Anterior cruciate ligament (ACL) injuries often lead to significant functional
      impairment, and are associated with increased risk for induction of degenerative
      joint disease. However, few studies have described the effect of ligament
      transection on the remaining intact knee ligaments. This study sought to
      determine specifically what impact combined ACL/medial collateral ligament (MCL)
      transection had on the remaining intact knee ligaments, particularly from the
      histological, biochemical, and molecular perspectives. Twenty weeks post-ACL/MCL
      transection, the cut ends of sheep MCLs were bridged by scar, while the posterior
      cruciate ligaments (PCLs) and lateral collateral ligaments (LCLs) seemed gross
      morphologically normal. Water content and cell density increased significantly in
      the MCL scars and the intact PCLs but were unchanged in the LCLs. Collagen fibril
      diameter distribution was significantly altered in both MCL scar tissue and
      uninjured PCLs from transected joints. MMP-13 mRNA levels in MCL scars and PCLs
      from ligament transected joints were increased, while TIMP-1 mRNA levels were
      significantly decreased in the PCLs only. This study has shown that some intact
      ligaments in injured joints are impacted by the injury. The joint appears to
      behave like an integrated organ system, with injury to one component affecting
      the other components as the "organ" attempts to adapt to the loss of integrity.

PMID- 17436315
TI  - Microscopic anatomy of brachial plexus branches in Wistar rats.
AB  - In the present study, we analyze the morphology and morphometry of the lateral
      proper digital nerve of the third finger, and of the proximal and distal segments
      of the ulnar, median, and radial nerves, in Wistar rats 4 or 7 weeks old. The
      fascicular area and diameter were generally significantly greater in the proximal
      compared to distal segments and tended to be larger in 7-week-old compared to 4
      week-old rats (e.g., median nerve area of 0.13 mm(2) for the proximal and 0.07
      mm(2) for distal segments in 4-week-old rats, and 0.17 and 0.10 mm(2),
      respectively, for the proximal and distal segments of 7-week-old rats). The
      number of fascicles was significantly greater while the number of myelinated
      fibers was significantly less in the distal segments (e.g., 1,359 and 509
      myelinated fibers, respectively, in the proximal and distal segments of the
      radial nerve 4-week-old rats). There was no significant difference in these
      parameters between the two age groups. The diameter of the myelinated fibers and
      their respective axons increased from 4 to 7 weeks of age (e.g., myelinated fiber
      diameter of 4.10 microm in 4-week-old animals and 4.7 microm in the ulnar nerve
      proximal segment of 7-week-old rats). The g-ratio regression line (axon diameter
      vs. fiber diameter quotient) was outlined for all the nerves studied here.
      Differences in myelinated fiber density were detected between the segments of the
      radial nerve, accompanying the number of myelinated fibers. Detailed knowledge of
      the microscopic anatomy of rat forelimb nerves provides control data for
      comparison with studies of experimentally induced neuropathies, which can shed
      more light on human neuropathies.

PMID- 17436316
TI  - A transcranial doppler study in interictal migraine and tension-type headache.
AB  - PURPOSE: To use transcranial Doppler (TCD) sonography to determine if patients
      with migraine without aura have interictal hemodynamic abnormalities compared
      with patients who have episodic tension-type headache (TH). METHODS: Thirty-six
      migraine patients without aura and 51 TH patients (age range, 16-50 years) who
      were diagnosed according to the criteria of the International Headache Society
      1988 participated in the study. Forty-four healthy volunteers, matched for age
      and sex, formed the control group. Time-averaged mean velocity (TAMV),
      pulsatility index (PI), and breath-holding index (BHI) were measured via TCD
      sonography in the middle cerebral artery. RESULTS: TAMV was higher in migraine
      without aura than in episodic TH (p = 0.034). There were no differences between
      groups regarding PI or BHI. CONCLUSION: Our findings support the arteriolar
      vasodilatation theory in migraine without aura.

PMID- 17436317
TI  - Prenatal diagnosis of fetal intra-abdominal umbilical vein varix: report of 2
      cases.
AB  - Fetal intra-abdominal umbilical vein varix (FIUVV) is a focal aneurysmal
      dilatation of the umbilical vein. Its clinical importance has not yet been
      clearly established, but it has been reported to be associated with increased
      fetal death rate (in nearly 44% of cases) and chromosomal abnormalities (in 12%
      of cases). We report 2 cases of FIUVV diagnosed via sonography in the third
      trimester.

PMID- 17436318
TI  - Unusual maternal vasculature in the placental periphery leading to the diagnosis
      of abdominal pregnancy at 25 weeks' gestation.
AB  - Abdominal pregnancy is a rare condition in which the fetus and placenta are
      located within the peritoneal cavity. Sonographic findings include visualization
      of the fetus separate from the uterus, failure to visualize the uterine wall
      between the fetus and urinary bladder, close approximation of fetal parts to the
      maternal abdominal wall, eccentric position or abnormal fetal attitude, and
      visualization of extrauterine placental tissue. We present an unusual case in
      which mid-trimester transabdominal color Doppler sonographic findings depicted
      unusual maternal vasculature in the placental periphery leading to the diagnosis
      of abdominal pregnancy. Postpartum maternal angiography confirmed these vessels
      as abnormal maternal arterial perfusion of the extrauterine placenta emanating
      from the uterine arteries and inferior epigastric arteries. Systematic review of
      the literature confirms that this is the first report of such sonographic
      manifestations of an abdominal pregnancy.

PMID- 17436319
TI  - Intima-media thickness of the abdominal aorta of neonate with different
      gestational ages.
AB  - PURPOSE: To determine aortic intima-media thickness (aIMT) values in newborns
      with different gestational ages and to asses the effect of antenatal steroids on
      aIMT. METHODS: Two hundred forty newborns from healthy mothers had their distal
      abdominal aIMT measured during abdominal sonographic examination. The neonates
      were divided into 4 groups (60 in each group) according to gestational age: group
      I (25-28 weeks), group II (29-32 weeks), group III (33-37 weeks), and group IV
      (38-42 weeks). RESULTS: The interobserver and intersubject intraclass correlation
      coefficient was 0.93 and 0.94, respectively. Mean aIMT was 0.316 mm, 0.335 mm,
      0.348 mm, and 0.385 mm, respectively, in group I, II, III, and IV, increasing
      significantly with gestational age at birth (p < 0.0001). There was no apparent
      effect of antenatal steroid use on aIMT. Multivariate regression models for mean
      aIMT demonstrated a significant association with aortic lumen diameter (p <
      0.0001). CONCLUSION: Abdominal aIMT can be reproducibly measured in neonates and
      may be a useful tool for epidemiologic studies.

PMID- 17436320
TI  - Pseudolymphoma of the liver: Sonographic findings and review of the literature.
AB  - We report a case of hepatic pseudolymphoma in a 67-year-old woman that was
      detected during an abdominal sonography screening. The lesion was further
      evaluated using CT, MRI, angiography, and contrast-enhanced sonography. The
      imaging features of this tumor are discussed herein. The diagnosis of
      pseudolymphoma was achieved via sonographically guided biopsy. The lesion
      regressed completely within 1 year.

PMID- 17436322
TI  - Conformation transition kinetics of Bombyx mori silk protein.
AB  - Time-resolved FTIR analysis was used to monitor the conformation transition
      induced by treating regenerated Bombyx mori silk fibroin films and solutions with
      different concentrations of ethanol. The resulting curves showing the kinetics of
      the transition for both films and fibroin solutions were influenced by the
      ethanol concentration. In addition, for silk fibroin solutions the protein
      concentration also had an effect on the kinetics. At low ethanol concentrations
      (for example, less than 40% v/v in the case of film), films and fibroin solutions
      showed a phase in which beta-sheets slowly formed at a rate dependent on the
      ethanol concentration. Reducing the concentration of the fibroin in solutions
      also slowed the formation of beta-sheets. These observations suggest that this
      phase represents a nucleation step. Such a nucleation phase was not seen in the
      conformation transition at ethanol concentrations > 40% in films or > 50% in silk
      fibroin solutions. Our results indicate that the ethanol-induced conformation
      transition of silk fibroin in films and solutions is a three-phase process. The
      first phase is the initiation of beta-sheet structure (nucleation), the second is
      a fast phase of beta-sheet growth while the third phase represents a slow
      perfection of previously formed beta-sheet structure. The nucleation step can be
      very fast or relatively slow, depending on factors that influence protein chain
      mobility and intermolecular hydrogen bond formation. The findings give support to
      the previous evidence that natural silk spinning in silkworms is nucleation
      dependent, and that silkworms (like spiders) use concentrated silk protein
      solutions, and careful control of the pH value and metallic ion content of the
      processing environment to speed up the nucleation step to produce a rapid
      conformation transition to convert the water soluble spinning dope to a tough
      solid silk fiber.

PMID- 17436321
TI  - Functional consequences of exchanging domains between LacI and PurR are mediated
      by the intervening linker sequence.
AB  - Homologue function can be differentiated by changing residues that affect binding
      sites or long-range interactions. LacI and PurR are two proteins that represent
      the LacI/GalR family (>500 members) of bacterial transcription regulators. All
      members have distinct DNA-binding and regulatory domains linked by approximately
      18 amino acids. Each homologue has specificity for different DNA and regulatory
      effector ligands; LacI and PurR also exhibit differences in allosteric
      communication between DNA and effector binding sites. A comparative study of LacI
      and PurR suggested that alterations in the interface between the regulatory
      domain and linker are important for differentiating their functions. Four
      residues (equivalent to LacI positions 48, 55, 58, and 61) appear particularly
      important for creating a unique interface and were predicted to be necessary for
      allosteric regulation. However, nearby residues in the linker interact with DNA
      ligand. Thus, differences observed in interactions between linker and regulatory
      domain may be the cause of altered function or an effect of the two proteins
      binding different DNA ligands. To separate these possibilities, we created a
      chimeric protein with the LacI DNA-binding domain/linker and the PurR regulatory
      domain (LLhP). If the interface requires homologue-specific interactions in order
      to propagate the signal from effector binding, then LLhP repression should not be
      allosterically regulated by effector binding. Experiments show that LLhP is
      capable of repression from lacO1 and, contrary to expectation, allosteric
      response is intact. Further, restoring the potential for PurR-like interactions
      via substitutions in the LLhP linker tends to diminish repression. These effects
      are especially pronounced for residues 58 and 61. Clearly, binding affinity of
      LLhP for the lacO1 DNA site is sensitive to long-range changes in the linker.
      This result also raises the possibility that mutations at positions 58 and 61 co
      evolved with changes in the DNA-binding site. In addition, repression measured in
      the absence and presence of effector ligand shows that allosteric response
      increases for several LLhP variants with substitutions at positions 48 and 55.
      Thus, while side chain variation at these sites does not generally dictate the
      presence or absence of allostery, the nature of the amino acid can modulate the
      response to effector.

PMID- 17436323
TI  - Site directed mutagenesis at position 193 of human trypsin 4 alters the rate of
      conformational change during activation: role of local internal viscosity in
      protein dynamics.
AB  - Upon activation of trypsinogen four peptide segments flanked by hinge glycine
      residues undergo conformational changes. To test whether the degree of
      conformational freedom of hinge regions affects the rate of activation, we
      introduced amino acid side chains of different characters at one of the hinges
      (position 193) and studied their effects on the rate constant of the
      conformational change. This structural rearrangement leading to activation was
      triggered by a pH-jump and monitored by intrinsic fluorescence change in the
      stopped-flow apparatus. We found that an increase in the size of the side chain
      at position 193 is associated with the decrease of the reaction rate constant. To
      analyze the thermodynamics of the reaction, temperature dependence of the
      reaction rate constants was examined in a wide temperature range (5-60 degrees C)
      using a novel temperature-jump/stopped-flow apparatus developed in our
      laboratory. Our data show that the mutations do not affect the activation energy
      (the exponential term) of the reaction, but they significantly alter the
      preexponential term of the Arrhenius equation. The effect of solvent viscosity on
      the rate constants of the conformational change during activation of the wild
      type enzyme and its R193G and R193A mutants was determined and evaluated on the
      basis of Kramers' theory. Based on this we propose that the reaction rate of this
      conformational transition is regulated by the internal molecular friction, which
      can be specifically modulated by mutagenesis in the hinge region.

PMID- 17436324
TI  - A simple way to compute protein dynamics without a mechanical model.
AB  - We found that in proteins the average atomic fluctuation is linearly related to
      the square of the atomic distance from the center of mass of the protein. Using
      this simple relation, we can accurately compute the temperature factors of
      proteins of a wide range of sizes and folds, and the correlation of the
      fluctuations in proteins. This simple relation provides a direct link between
      protein dynamics and the static protein's geometrical shape and offers a simple
      way to compute protein dynamics without either long time trajectory integration
      or any matrix operations.

PMID- 17436325
TI  - SVM-Cabins: prediction of solvent accessibility using accumulation cutoff set and
      support vector machine.
AB  - A number of methods for predicting levels of solvent accessibility or accessible
      surface area (ASA) of amino acid residues in proteins have been developed. These
      methods either predict regularly spaced states of relative solvent accessibility
      or an analogue real value indicating relative solvent accessibility. While
      discrete states of exposure can be easily obtained by post prediction assignment
      of thresholds to the predicted or computed real values of ASA, the reverse, that
      is, obtaining a real value from quantized states of predicted ASA, is not
      straightforward as a two-state prediction in such cases would give a large real
      valued errors. However, prediction of ASA into larger number of ASA states and
      then finding a corresponding scheme for real value prediction may be helpful in
      integrating the two approaches of ASA prediction. We report a novel method of
      obtaining numerical real values of solvent accessibility, using accumulation
      cutoff set and support vector machine. This so-called SVM-Cabins method first
      predicts discrete states of ASA of amino acid residues from their evolutionary
      profile and then maps the predicted states onto a real valued linear space by
      simple algebraic methods. Resulting performance of such a rigorous approach using
      13-state ASA prediction is at least comparable with the best methods of ASA
      prediction reported so far. The mean absolute error in this method reaches the
      best performance of 15.1% on the tested data set of 502 proteins with a
      coefficient of correlation equal to 0.66. Since, the method starts with the
      prediction of discrete states of ASA and leads to real value predictions,
      performance of prediction in binary states and real values are simultaneously
      optimized.

PMID- 17436327
TI  - Correlation of tracheal smooth muscle function with structure and protein
      expression during early development.
AB  - With increased survival of premature infants, understanding the impact of
      development on airway function and structure is imperative. Airway smooth muscle
      plays a primary role in the modulation of airway function. The purpose of this
      study is to correlate the functional maturation of airway smooth muscle during
      the perinatal period with structural alterations at the cellular,
      ultrastructural, and molecular levels. Length-tension and dose-response analyses
      were performed on tracheal rings acquired from preterm and term newborn lambs.
      Subsequent structural analyses included isolated airway smooth muscle cell
      length, electron microscopy, and myosin heavy chain isoform expression
      measurements. Functionally the compliance, contractility, and agonist sensitivity
      of the tracheal rings matured during preterm to term development. Structurally,
      isolated cell lengths and electron microscopic ultrastructure were not
      significantly altered during perinatal development. However, expression of myosin
      heavy chain isoforms increased significantly across the age range analyzed,
      correlating with the maturational increase in smooth muscle contractility. In
      conclusion, the developmental alterations in tracheal function appear due, in
      part, to enhanced smooth muscle myosin heavy chain expression.

PMID- 17436328
TI  - Pilot study of safety and tolerability of inhaled hypertonic saline in infants
      with cystic fibrosis.
AB  - Inhaled hypertonic saline (HS) positively affects both lung function and
      pulmonary exacerbations in children and adults with cystic fibrosis (CF). Early
      initiation of treatment may potentially reduce lung function decline and improve
      outcome of CF patients. However, the safety and tolerability of HS have not been
      established in infants and young children. We conducted a prospective trial of
      inhaled HS in infants with CF. Raised volume rapid thoracoabdominal compression
      (RVRTC) maneuvers were performed at baseline, 10 min after salbutamol inhalation
      and 15 min after inhalation of a 7% HS solution. Oxygen saturation, respiratory
      rate, heart rate, and cough frequency were recorded during each inhalation. A
      clinically important change in lung function was defined a priori as a change in
      FEV 0.5 of > or =20%. Thirteen infants (5 female) aged 25-140 weeks were enrolled
      in the study. Overall, there was no difference between FEV(0.5) or FEF(25-75) at
      baseline, after bronchodilator or after HS. Respiratory and heart rate as well as
      oxygen saturation remained stable during inhalation of the HS. Three infants had
      cough during inhalation; one of the infants woke up due to cough but recovered
      within 5 min. No other side effects were observed during or immediately after
      inhalation. There was no difference in microbiologic yield between pre- and post
      HS throat swabs. In this pilot study, inhalation of HS was well tolerated in CF
      infants. These results support a study of the efficacy of HS in this age group.

PMID- 17436329
TI  - Ultrastructural and hormonal changes in the pineal-testicular axis following
      arecoline administration in rats.
AB  - Arecoline is an alkaloid of betel nut of Areca catechu. Betel nut is chewed by
      millions of people in the world and it causes oral and hepatic cancers in human.
      It has therapeutic value for the treatment of Alzheimer and schizophrenia.
      Arecoline has immunosuppressive, mutagenic and genotoxic effects in laboratory
      animals. It also affects endocrine functions. The objective of this study was to
      investigate the effects of arecoline on pineal-testicular axis in rats. Since
      pineal activity is different between day and night, the current study is
      undertaken in both the photophase and scotophase. The findings were evaluated by
      ultrastructural and hormonal studies of pineal and testicular Leydig cells, with
      quantitations of fructose and sialic acid of sex accessories. Arecoline treatment
      (10 mg/kg body weight daily for 10 days) caused suppression of pineal activity at
      ultrastructural level by showing dilatation of the cisternae of the rough
      endoplasmic reticulum (RER), large autophagosome-like bodies with swollen
      mitochondrial cristae, numerous lysosomes, degenerated synaptic ribbons and
      reduced number of synaptic-like microvesicles. Moreover, pineal and serum N
      acetylserotonin and melatonin levels were decreased with increased serotonin
      levels in both the gland and serum. In contrast, testicular Leydig cell activity
      was stimulated with abundance of smooth endoplasmic reticulum (SER), electron
      dense core vesicles and vacuolated secretory vesicles, and increased testosterone
      level in the arecoline recipients. Consequently, the testosterone target, like
      prostate, was ultrastructurally stimulated with abundance of RER and accumulation
      of secretory vesicles. Fructose and sialic acid concentrations were also
      significantly increased respectively in the coagulating gland and seminal
      vesicle. These results were more significant in the scotophase than the
      photophase. The findings suggest that arecoline inhibits pineal activity, but
      stimulates testicular function (testosterone level) and its target organs
      presumably via muscarinic cholinergic receptor in rats.

PMID- 17436330
TI  - Differential expression and dynamic changes of SOX3 during gametogenesis and sex
      reversal in protogynous hermaphroditic fish.
AB  - SOX3 has been suggested to play significant roles in gametogenesis and gonad
      differentiation of vertebrates, but the exact cellular localization evidence is
      insufficient and controversial. In this study, a protogynous hermaphrodite fish
      Epinephelus coioides is selected to analyze EcSox3 differential expression and
      the expression pattern in both processes of oogenesis and spermatogenesis by
      utilizing the advantages that gonad development undergoes transition from ovary
      to intersexual gonad and then to testis, and primordial germ cells and different
      stage cells during oogenesis and spermatogenesis are synchronously observed in
      the transitional gonads. The detailed and clear immunofluoresence localization
      indicates that significantly differential expression and dynamic changes of Sox3
      occur in the progresses of gametogenesis and sex reversal, and EcSOX3 protein
      exists in the differentiating primordial germ cells, oogonia, and different stage
      oocytes of ovaries, and also in the differentiating primordial germ cells and the
      Sertoli cells of testis. One important finding is that the EcSox3 expression is a
      significant time point for enterable gametogenesis of primordial germ cells
      because EcSOX3 is obviously expressed and localized in primordial germ cells. As
      EcSox3 continues to express, the EcSOX3-positive primordial germ cells develop
      toward oogonia and then oocytes, whereas when EcSox3 expression is ceased, the
      EcSOX3-positive primordial germ cells develop toward spermatogonia. Therefore,
      the current finding of EcSOX3 in the differentiating primordial germ cells again
      confirms the potential regulatory role in oogenesis and germ cell
      differentiation. The data further suggest that SOX3, as a transcription factor,
      might have more important roles in oogenesis than in spermatogenesis.

PMID- 17436331
TI  - Masticatory motor patterns in ungulates: a quantitative assessment of jaw-muscle
      coordination in goats, alpacas and horses.
AB  - We investigated patterns of jaw-muscle coordination during rhythmic mastication
      in three species of ungulates displaying the marked transverse jaw movements
      typical of many large mammalian herbivores. In order to quantify consistent motor
      patterns during chewing, electromyograms were recorded from the superficial
      masseter, deep masseter, posterior temporalis and medial pterygoid muscles of
      goats, alpacas and horses. Timing differences between muscle pairs were evaluated
      in the context of an evolutionary model of jaw-muscle function. In this model,
      the closing and food reduction phases of mastication are primarily controlled by
      two distinct muscle groups, triplet I (balancing-side superficial masseter and
      medial pterygoid and working-side posterior temporalis) and triplet II (working
      side superficial masseter and medial pterygoid and balancing-side posterior
      temporalis), and the asynchronous activity of the working- and balancing-side
      deep masseters. The three species differ in the extent to which the jaw muscles
      are coordinated as triplet I and triplet II. Alpacas, and to a lesser extent,
      goats, exhibit the triplet pattern whereas horses do not. In contrast, all three
      species show marked asynchrony of the working-side and balancing-side deep
      masseters, with jaw closing initiated by the working-side muscle and the
      balancing-side muscle firing much later during closing. However, goats differ
      from alpacas and horses in the timing of the balancing-side deep masseter
      relative to the triplet II muscles. This study highlights interspecific
      differences in the coordination of jaw muscles to influence transverse jaw
      movements and the production of bite force in herbivorous ungulates.

PMID- 17436332
TI  - Identification of breed-specific DNA polymorphisms for a simple and unambiguous
      screening system in germline chimeric chickens.
AB  - In the chicken, Dominant white is one of the major loci affecting feather color.
      Germline chimeric chickens are identified by testcross analysis using this
      genetic marker. The testcross, however, is a time-consuming and laborious
      procedure, resulting in the need for a faster and simpler molecular method. A
      recent study showed that Dominant white was exclusively associated with a 9-bp
      insertion in the PMEL17 gene. We searched for breed-specific sequence
      polymorphisms in the PMEL17 gene among White Leghorn (WL) (white feather), Korean
      Ogol Chicken (KOC) (black feather), and Barred Plymouth Rock (grayish-white, each
      feather regularly crossed with parallel blue-black bars). In addition to the 9-bp
      insertion, WLs and KOCs have unique bases in single nucleotide polymorphisms
      (SNPs) at the 1,777th and 3,118th bases in the PMEL17 gene. To detect these
      sequence polymorphisms, allele-specific polymerase chain reaction (AS-PCR) was
      performed, which successfully distinguished the different breeds. We confirmed
      the ability of the AS primers to detect germline chimerism. This simple method
      can be widely used for the screening of germline chimeric chickens.

PMID- 17436333
TI  - Fluorescence-lifetime imaging of DNA-dye interactions within continuous-flow
      microfluidic systems.

PMID- 17436334
TI  - Bacterial translocation during liver transplantation: a randomized trial
      comparing conventional with venovenous bypass vs. piggyback methods.
AB  - The aim of this study was to evaluate the bacterial translocation in liver
      transplantation (LT), comparing the conventional and the piggyback methods. A
      total of 32 patients were randomized into the 2 groups. Samples of blood were
      collected from the radial artery, portal vein (PV) and hepatic vein (HV), in up
      to 120 minutes postreperfusion. The samples were sent for endotoxin level, as
      well as samples up to 2 minutes post-perfusion were sent to culture. Hepatic
      artery and PV blood flows were measured at postreperfusion collection times. The
      results analyzed were: endotoxin concentration, its quantity, and hepatic
      clearance. The statistical treatment consisted of analyzing each group's mean
      profile. The analysis for endotoxin concentration in the radial artery was the
      deviation related to presurgery measure, and in the PV the deviation related to
      preclamping (PC) measure. The overall mean level of endotoxin concentration was
      0.99 EU/mL in the artery, 1.30 EU/mL in the PV, and 1.22 EU/mL in the HV. The
      deviation was significant in the portal (P = 0.0031), but not in the artery
      samples (P = 0.2092). We detected a significant quantity of endotoxin in the
      artery and in the portal and the HVs (P < 0.001). There was no difference between
      the 2 groups and no hepatic clearance of endotoxin was detected either (P =
      0.1515). All the cultures were negative. In conclusion, the study detected a
      significant translocation of endotoxin, but not of bacteria. The study also
      detected the absence of endotoxin hepatic clearance in both the piggyback and the
      conventional methods without any difference between them.

PMID- 17436335
TI  - Proteome analysis of the culture environment supporting undifferentiated mouse
      embryonic stem and germ cell growth.
AB  - The therapeutical interest of pluripotent cells and ethical issues related to the
      establishment of human embryonic stem cell (ESC) or embryonic germ cell (EGC)
      lines raise the understanding of the mechanism underlying pluripotency to a
      fundamental issue. Establishing a protein pluripotency signature for these cells
      can be complicated by the presence of unrelated proteins produced by the culture
      environment. Here, we have analyzed the environment supporting ESC and EGC
      growth, and established 2-D reference maps for each constituent present in this
      culture environment: mouse embryonic fibroblast feeder cells, culture medium (CM)
      and gelatin. The establishment of these reference maps is essential prior to the
      study of ESC and EGC specific proteomes. Indeed, these maps can be subtracted
      from ESC or EGC maps to allow focusing on spots specific for ESCs or EGCs. Our
      study led to the identification of 110 unique proteins from fibroblast feeder
      cells and 23 unique proteins from the CM, which represent major contaminants of
      ESC and EGC proteomes. For gelatin, no collagen-specific proteins were
      identified, most likely due to difficulties in resolution and low quantities.
      Furthermore, no differences were observed between naive and conditioned CM.
      Finally, we compared these reference maps to ESC 2-D gels and isolated 17 ESC
      specific spots. Among these spots, proteins that had already been identified in
      previous human and mouse ESC proteomes were identified but no apparent ESC
      specific pluripotency marker could be identified. This work represents an
      essential step in furthering the knowledge of environmental factors supporting
      ESC and EGC growth.

PMID- 17436336
TI  - Implementation of an adaptive group sequential design in a bioequivalence study.
AB  - The study design was a multi-center, multiple-dose, randomized, open-label, 2 x 2
      crossover study in patients with advanced solid tumors. Each patient was
      randomized to receive the test formulation or the reference formulation of the
      drug. The primary objective of the study was to demonstrate the bioequivalence of
      the test formulation T relative to the reference formulation R. The primary
      pharmacokinetic endpoints were AUC and Cmax. Since there were different
      bioequivalence criteria, different endpoints, with different and highly variable
      coefficients of variation, an adaptive design with a stopping rule for early
      establishing the bioequivalence as well as early stopping for futility with a
      flexible information-based monitoring based on error spending approach was
      implemented to manage uncertainty in assumptions of variability and expected slow
      enrollment rates.

PMID- 17436337
TI  - Prediction of lateral pelvic node involvement in low rectal cancer by
      conventional computed tomography.
AB  - BACKGROUND: The clinical significance of lateral pelvic lymphatic spread in
      rectal cancer remains unknown. The present study aimed to assess the accuracy of
      preoperative computed tomography (CT) for prediction of lateral node involvement
      in patients with low rectal cancer and to determine the prognostic significance
      of extended lateral node dissection. METHODS: A total of 109 patients with
      primary low rectal cancer were enrolled in this prospective cohort study. The
      preoperative CT findings were compared with the histopathological results and
      with follow-up data. RESULTS: CT diagnosed lateral lymph node status with high
      accuracy (sensitivity 95 per cent, specificity 94 per cent), in marked contrast
      to mesorectal node status. Of 68 patients who had R0 resection without lateral
      node dissection, only two developed pelvic wall recurrence during median follow
      up of 4.1 years. Metastatic nodes in the lateral pelvic region were significantly
      larger than those in the mesorectum (P < 0.001). CONCLUSION: CT accurately
      predicted lateral lymph node status in low rectal cancer, allowing preoperative
      identification of patients who might benefit from extended lateral node
      dissection.

PMID- 17436338
TI  - Sentinel node biopsy for breast cancer larger than 3 cm in diameter.
AB  - BACKGROUND: Sentinel node biopsy (SNB) is a standard staging procedure in early
      breast cancer. Its suitability for larger tumours has been questioned. This study
      evaluated the reliability of SNB in women with invasive breast cancer larger than
      3 cm in diameter who were clinically axillary node negative. METHODS: Some 109
      women with a tumour larger than 3 cm on pathological analysis were identified
      from the Swedish prospective SNB database. They were included if a completion
      axillary clearance was planned, regardless of SNB results. RESULTS: The sentinel
      node detection rate was 103 (94.5 per cent) of 109. The overall false-negative
      rate was eight (13 per cent) of 64. Although a preoperative diagnosis of
      multifocal tumour was an exclusion criterion, 16 such cases were revealed on
      postoperative pathological examination. The false-negative rate in this subgroup
      was higher than that in women with a unifocal tumour (four (31 per cent) of 13
      versus four (8 per cent) of 51; P = 0.012). No other significant predictors of a
      false-negative sentinel node biopsy were identified. CONCLUSION: SNB is feasible
      in patients with unifocal breast tumours larger than 3 cm. When large tumour size
      coincides with multifocality, however, the false-negative rate seems to be
      increased and a completion axillary clearance should be considered even if the
      SNB is negative.

PMID- 17436339
TI  - Conformational solution studies of the anti-microbial temporin A retro-analogues
      by using NMR spectroscopy.
AB  - Temporin A (TA) is a small, basic and highly hydrophobic peptide, isolated from
      the skin of the European red frog, Rana temporaria. The TA (FLPLIGRVLSGIL-NH2)
      displays a broad spectrum of anti-microbial activity against Gram-positive
      bacteria and fungi Candida albicans. In this study we investigate the solution
      structure of two TA retro-analogues, (6-1)(7-13)-TA (GILPLFRVLSGIL-NH2) and retro
      TA (LIGSLVRGILPLF-NH2) by using nuclear magnetic resonance (NMR). The 3D solution
      structure of the analogues was established by using inter-proton distances and
      vicinal coupling constants in the Simulated Annealing (SA) calculations (XPLOR
      program). The NMR conformational studies show the existence of the helical
      structure in the middle part of the (6-1)(7-13)-TA peptide and an unordered
      structure of the retro-TA analogue under the D3-TFE/H2O (3:7, v/v) conditions.
      Our investigations have shown that the hydrophobic cluster at N-terminus with the
      Pro amino acid residue in position 3 or 4, the helical structure and the
      amphipathic character of the peptide are responsible for the anti-microbial
      activity of the TA analogues.

PMID- 17436340
TI  - Beam-type collisional activation of polypeptide cations that survive ion/ion
      electron transfer.
AB  - Doubly protonated peptides that undergo an electron transfer reaction without
      dissociation in a linear ion trap can be subjected to beam-type collisional
      activation upon transfer from the linear ion trap into an adjacent mass analyzer,
      as demonstrated here with a hybrid triple quadrupole/linear ion trap system. The
      activation can be promoted by use of a DC offset difference between the ion trap
      used for reaction and the ion trap into which the products are injected of 12-16
      V, which gives rise to energetic collisions between the transferred ions and the
      collision/bath gas employed in the linear ion trap used for ion/ion reactions.
      Such a process can be executed routinely on hybrid linear ion trap/triple
      quadrupole tandem mass spectrometers and is demonstrated here with several model
      peptides as well as a few dozen tryptic peptides. Collisional activation of the
      peptide precursor ions that survive electron transfer frequently provides
      structural information that is absent from the precursor ions that fragment
      spontaneously upon electron transfer. The degree to which additional structural
      information is obtained by collisional activation of the surviving singly charged
      peptide ions depends upon peptide size. Little or no additional structural
      information is obtained from small peptides (<8 residues) due to the high
      electron transfer dissociation (ETD) efficiencies noted for these peptides as
      well as the extensive sequence information that tends to be forthcoming from ETD
      of such species. Collisional activation of the surviving electron transfer
      products provided greatest benefit for peptides of 8-15 residues.

PMID- 17436341
TI  - Peptides and proteins in a confined environment: NMR spectra at natural isotopic
      abundance.
AB  - Confinement of proteins and peptides in a small inert space mimics the natural
      environment of the cell, allowing structural studies in conditions that stabilize
      folded conformations. We have previously shown that confinement in polyacrylamide
      gels (PAGs) is sufficient to induce a change in the viscosity of the aqueous
      solution without changing the composition and temperature of the solvent. The
      main limitation of a PAG to run NMR experiments in a confined environment is the
      need for labelling the peptides. Here we report the use of the agarose gel to run
      the NMR spectra of proteins and peptides. We show that agarose gels are
      completely transparent in NMR experiments, relieving the need for labelling.
      Although it is necessary to expose biomolecules to fairly high temperatures
      during sample preparation, we believe that this is not generally an obstacle to
      the study of peptides, and found that the method is also compatible with
      temperature-resistant proteins. The mesh of agarose gels is too wide for direct
      effects of confinement on the stability of proteins but confinement can be easily
      exploited to interact the proteins with other reagents, including crowding
      macromolecules that can eventually lead to fold stabilization. The use of these
      gels is ideally suited for low-temperature studies; we show that a very flexible
      peptide at subzero temperatures is stabilized into a well-folded conformation.

PMID- 17436342
TI  - The use of Fmoc-Lys(Pac)-OH and penicillin G acylase in the preparation of novel
      semisynthetic insulin analogs.
AB  - In this paper, we present the detailed synthetic protocol and characterization of
      Fmoc-Lys(Pac)-OH, its use for the preparation of octapeptides H-Gly-Phe-Tyr-N
      MePhe-Thr-Lys(Pac)-Pro-Thr-OH and H-Gly-Phe-Phe-His-Thr-Pro-Lys(Pac)-Thr-OH by
      solid-phase synthesis, trypsin-catalyzed condensation of these octapeptides with
      desoctapeptide(B23-B30)-insulin, and penicillin G acylase catalyzed cleavage of
      phenylacetyl (Pac) group from Nepsilon-amino group of lysine to give novel
      insulin analogs [TyrB25, N-MePheB26,LysB28,ProB29]-insulin and [HisB26]-insulin.
      These new analogs display 4 and 78% binding affinity respectively to insulin
      receptor in rat adipose membranes.

PMID- 17436343
TI  - Antidepressants in children and adolescents--changes in utilisation after safety
      warnings.
AB  - BACKGROUND: Antidepressants, in particular selective serotonin reuptake
      inhibitors, are one of the most commonly used classes of psychotropic drug in
      children and adolescents. Beginning in June 2003, evidence emerged suggesting
      that antidepressants may increase risk of suicidal behaviour in young people.
      This evidence was accompanied by national and international guidelines cautioning
      against use of many antidepressants in young people. This study aimed to assess
      whether these safety warnings have impacted upon antidepressant utilisation
      rates. METHOD: This study was based at a metropolitan health service
      incorporating children's and adult hospitals. Total service utilisation of
      antidepressants was extracted from pharmacy software for the period January 2002
      to December 2005. Monthly utilisation rates were computed for adults and
      children's services as defined daily doses (DDD) per occupied bed days. Changes
      in utilisation over time were examined for children and adults. RESULTS: There
      was a significant relationship between time and antidepressant utilisation in
      children and adolescents, where antidepressant use decreased over time (R =
      0.474; t = -3.66; p < 0.01), and in particular, use of SSRIs (R = 0.461; t = 
      3.52; p < 0.01). In contrast, use of SSRIs (R = 0.587; t = 4.91; p < 0.001) and
      all antidepressants (R = 0.327; t = 2.35; p < 0.05) increased over time in
      adults. CONCLUSIONS: National and international warnings about safety of
      antidepressants in children and adolescents appear to have influenced local
      utilisation of these medications in young people but not in adults. Further
      research is required to determine optimal utilisation rates.

PMID- 17436344
TI  - Activity and stability of human kallikrein-2-specific linear and cyclic peptide
      inhibitors.
AB  - Human glandular kallikrein (KLK2) is a highly prostate-specific serine protease,
      which is mainly excreted into the seminal fluid, but part of which is also
      secreted into circulation from prostatic tumors. Since the expression level of
      KLK2 is elevated in aggressive tumors and it has been suggested to mediate the
      metastasis of prostate cancer, inhibition of the proteolytic activity of KLK2 is
      of potential therapeutic value. We have previously identified several KLK2
      specific linear peptides by phage display technology. Two of its synthetic
      analogs, A R R P A P A P G (KLK2a) and G A A R F K V W W A A G (KLK2b), show
      specific inhibition of KLK2 but their sensitivity to proteolysis in vivo may
      restrict their potential use as therapeutic agents. In order to improve the
      stability of the linear peptides for in vivo use, we have prepared cyclic analogs
      and compared their biological activity and their structural stability. A series
      of cyclic variants with cysteine bridges were synthesized. Cyclization
      inactivated one peptide (KLK2a) and its derivatives, while the other peptide
      (KLK2b) and its derivatives remained active. Furthermore, backbone cyclization of
      KLK2b improved significantly the resistance against proteolysis by trypsin and
      human plasma. Nuclear magnetic resonance studies showed that cyclization of the
      KLK2b peptides does not make the structures more rigid. In conclusion, we have
      shown that backbone cyclization of KLK2 inhibitory peptides can be used to
      increase stability without losing biological activity. This should render the
      peptides more useful for in vivo applications, such as tumor imaging and prostate
      cancer targeting.

PMID- 17436345
TI  - Application of gel-phase 19F NMR spectroscopy for optimization of solid-phase
      synthesis of a hydrophobic peptide from the signal sequence of the mucin MUC1.
AB  - This paper describes the manual Fmoc/t-Bu solid-phase synthesis of a difficult
      nine-residue hydrophobic peptide LLLLTVLTV from one of the signal sequences that
      flank the tandem repeat of the mucin MUC1. Gel-phase 19F NMR spectroscopy was
      used as a straightforward method for optimization of the solid-phase synthesis.
      Different approaches were applied for comparative studies. The strategy based on
      modified solid-phase conditions using DIC/HOAt for coupling, DBU for Fmoc
      deprotection, and the incorporation of the pseudo proline dipeptide Fmoc-Leu
      Thr(psiMe, Me pro)-OH as a backbone-protecting group was found to be superior
      according to gel-phase 19F NMR spectroscopy. Implementation of the optimized Fmoc
      protocol enabled an effective synthesis of signal peptide LLLLTVLTV.

PMID- 17436346
TI  - Chinese demented inpatients admitted following a suicide attempt: a case series.
AB  - OBJECTIVE: Suicide attempt is rarely reported in dementia. This study explores
      the clinical and phenomenological aspects as well as the treatment of Chinese
      demented patients who have attempted suicide. METHODS: During a 1-year period,
      demented patients admitted to a geropsychiatric unit as a result of suicide
      attempt were investigated for factors related to suicide attempt, such as motives
      and method. RESULTS: In this 1-year survey, seven demented patients (11.7% of all
      demented patients) were admitted immediately following a suicide attempt. All
      seven patients had mild or moderate dementia. Three had significant clinical
      depression symptoms on admission. In all patients, delusions were the primary
      cause of suicide attempt. Their suicidal ideations were improved with
      antipsychotic and antidepressant treatment. CONCLUSION: These cases, taken
      together, suggest that suicide attempt can occur in patients with dementia. It is
      important for clinicians to be aware of the risk of suicide in patients with
      dementia, especially those associated with delusions, even if they have no major
      depression or suicide attempt history. Antidepressants and antipsychotics may
      play a critical role in the treatment of suicide attempt in dementia.

PMID- 17436347
TI  - Simultaneous tuning of chemical composition and topography of copolymer surfaces:
      micelles as building blocks.
AB  - A simple method is described for controlling the surface chemical composition and
      topography of the diblock copolymer poly(styrene)-b-poly(dimethylsiloxane)(PS-b
      PDMS) by casting the copolymer solutions from solvents with different
      selectivities. The surface morphology and chemical composition were characterized
      by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS),
      respectively, and the wetting behavior was studied by water contact angle (CA)
      and sliding angle (SA) and by CA hysteresis. Chemical composition and morphology
      of the surface depend on solvent properties, humidity of the air, solution
      concentration, and block lengths. If the copolymer is cast from a common solvent,
      the resultant surface is hydrophobic, with a flat morphology, and dominated by
      PDMS on the air side. From a PDMS-selective solvent, the surface topography
      depends on the morphology of the micelles. Starlike micelles give rise to a
      featureless surface nearly completely covered by PDMS, while crew-cut-like
      micelles lead to a rough surface with a hierarchical structure that consists
      partly of PDMS. From a PS-selective solvent, however, surface segregation of PDMS
      was restricted, and the surface morphology can be controlled by vapor-induced
      phase separation. On the basis of the tunable surface roughness and PDMS
      concentration on the air side, water repellency of the copolymer surface could be
      tailored from hydrophobic to superhydrophobic. In addition, reversible switching
      behavior between hydrophobic and superhydrophobic can be achieved by exposing the
      surface to solvents with different selectivities.

PMID- 17436348
TI  - Molecular dynamics simulations of CN- dynamics and spectroscopy in myoglobin.
AB  - The vibrational dynamics of the cyanide anion and the heme group in MbCN (CN
      complexed to Myoglobin) are investigated using molecular dynamics simulations. A
      previously calculated quantum-chemical heme-ligand potential-energy surface
      together with a three-center charge model for the iron-ligand center that
      captures both polarization and ligand-to-metal charge transfer allows for a
      detailed description of the interactions around the active site. It is found that
      the CN binding orientation (Fe--CN or Fe--NC) to the heme affects the stretching
      frequency of the ligand, with a 25 cm-1 difference in the fundamental wavenumber
      between the two orientations as well as a change in bond length. The charge model
      also captures such crucial interactions as the possible hydrogen bond between the
      ligand and the His64 residue. This interaction is weakened when the ligand binds
      in the Fe--NC conformation but is also sensitive to the protonation state of
      His64. The structural changes around the active site, the observation of water
      penetration for the Fe--NC conformation, the computed IR spectrum, and the
      energetics suggest that the Fe--CN conformation with Hisepsilon64 is the most
      likely one. The water accessibility of the active site is also found to be
      related to the protonation state of His64. The presence of water in the active
      site could also affect the IR band of the C--N stretch mode. Thus, IR
      spectroscopy of the C--N stretch is a potentially useful reporter of ligand
      isomers and active-site structure.

PMID- 17436349
TI  - Repetitive reversible labeling of proteins at polyhistidine sequences for single
      molecule imaging in live cells.
AB  - Sensitive live-cell fluorescence microscopy and single-molecule imaging are
      severely limited by rapid photobleaching of fluorescent probes. Herein, we show
      how to circumvent this problem using a novel, generic labeling strategy. Small
      nickel-nitrilotriacetate fluorescent probes are reversibly bound to
      oligohistidine sequences of exposed proteins on cell surfaces, permitting
      selective observation of the proteins by fluorescence microscopy. Photobleached
      probes are removed by washing and replaced by new fluorophores, thus enabling
      repetitive acquisition of single-molecule trajectories on the same cell and
      allowing variation of experimental conditions between acquisitions. This method
      offers free choice of fluorophores while being minimally perturbing. The strength
      of the method is demonstrated by labeling engineered polyhistidine sequences of
      the serotonin-gated 5-HT(3) receptor on the surface of live mammalian cells.
      Single-molecule microscopy reveals pronounced heterogeneous mobility patterns of
      the 5-HT(3) receptor. After activating the receptor with serotonin, the number of
      immobile receptors increases substantially, which might be important for receptor
      regulation at synapses.

PMID- 17436351
TI  - Structure-based calculation of binding affinities of alpha 2A-adrenoceptor
      agonists.

PMID- 17436352
TI  - How (77)Se NMR chemical shifts originate from pre-alpha, alpha, beta, and gamma
      effects: interpretation based on molecular orbital theory.
AB  - Plain rules founded in a theoretical background are presented that can be used to
      determine the structure of selenium compounds on the basis of delta(Se) data and
      to predict delta(Se) data from a given structure with satisfactory accuracy. As a
      first step to establish such rules, the origin of delta(Se) is elucidated on the
      basis of MO theory. The Se(2-) ion was chosen as the standard for the analysis.
      The concept of the pre-alpha effect is proposed, which is defined as the
      downfield shift due to protonation of a lone-pair orbital of Se. The pre-alpha
      effect of two protons in H(2)Se is explained by the generation of double sigma(Se
      -H) and sigma*(Se--H) through protonation of the spherical Se(2-) ion. The
      orbitals, together with n(p)(Se), result in effective transitions for the pre
      alpha effect. The alpha effect is the downfield shift caused by the replacement
      of Se--H by Se--Me. The extension of HOMO-2 [4p(y)(Se)], HOMO-1 [4p(x)(Se)], and
      HOMO [4p(z)(Se)] over the whole Me(2)Se molecule is mainly responsible for the
      alpha effect. The beta effect originates not from the occupied-to-unoccupied
      (psi(i)-->psi(a)) transitions but from the occupied-to-occupied (psi(i)-->psi(j))
      transitions. Although psi(i)-->psi(j) transitions contribute to upfield shifts in
      Me(2)Se, the magnitudes become smaller as the methyl protons are substituted by
      Me groups one after another. The gamma effect of upfield shifts is also analyzed,
      although complex. The effect of p(Se)-pi(C==C) conjugation is analyzed in
      relation to the orientational effect. Contributions from each MO (psi(i)) and
      each psi(i)-->psi(a) transition are evaluated separately, by using a utility
      program derived from the Gaussian 03 program suite (NMRANAL-NH03G). The treatment
      enables us to visualize and understand the origin of (77)Se NMR chemical shifts.

PMID- 17436353
TI  - An intermediate for the clean synthesis of ionic liquids: isolation and crystal
      structure of 1,3-dimethylimidazolium hydrogen carbonate monohydrate.
AB  - 1,3-Dimethylimidazolium-2-carboxylate and carbonic acid have been used to prepare
      a 1,3-dimethylimidazolium hydrogen carbonate salt by means of a Krapcho reaction.
      The ability to form hydrogen carbonate azolium salts allows for them to be used
      as precursors for fast, efficient, environmentally benign, and halide-free
      syntheses of many ionic liquids by a simple, acid-base reaction of virtually any
      acid (inorganic, organic, and organic noncarboxylic) with a pK(a) less than that
      of HCO(3) (-). Additionally, the kinetics of this reaction can be accelerated by
      employing catalytic amounts of DMSO (a traditional Krapcho solvent used in
      decarboxylation reactions) to catalyze the decarboxylation. The crystal structure
      of 1,3-dimethylimidazolium hydrogen carbonate monohydrate is the first example of
      an imidazolium-based hydrogen carbonate salt. There is a strong 2D hydrogen
      bonded network with facially pi-stacked imidazolium cations located in the
      cavities created by this framework.

PMID- 17436354
TI  - Chiral supramolecular assemblies of a squaraine dye in solution and thin films:
      concentration-, temperature-, and solvent-induced chirality inversion.
AB  - We prepared novel cholesterol-appended squaraine dye 1 and model squaraine dye 2
      and investigated their aggregation behavior in solution and thin films using
      photophysical, chiroptical, and microscopic techniques. Investigations on the
      dependence of aggregation on solvent composition (good/poor, CHCl3/CH3CN)
      demonstrated that squaraine dye 1 forms two novel H-type chiral supramolecular
      assemblies with opposite chirality at different good/poor solvent compositions.
      Model compound 2 formed J-type achiral assemblies under similar conditions. The
      supramolecular assembly of 1 observed at lower fractions of the poor solvent
      could be assigned to the thermodynamically stable form, while a kinetically
      controlled assembly is formed at higher fractions of the poor solvent. This
      assignment is evidenced by temperature- and concentration-dependent experiments.
      With increasing temperature, the chirality of the kinetically controlled
      aggregate was lost and, on cooling, the aggregate with the opposite chirality was
      formed. On further heating and cooling the aggregates thus formed resulted in no
      significant changes in chirality, that is they are thermodynamically stable.
      Similarly, at lower concentrations, the thermodynamically stable form exists, but
      at higher concentration aggregation was found to proceed with kinetic control.
      Based on these observations it can be assumed that formation of the kinetically
      controlled assembly might be largely dependent on the presence of the nonpolar
      cholesterol moiety as well as the amount of poor solvent present. However, under
      solvent-free conditions, structurally different aggregates were observed when
      drop cast from solutions containing monomer, whereas a left-handed CD signal
      corresponding to the thermodynamically controlled assemblies was observed from
      pre-aggregated solutions.

PMID- 17436355
TI  - A method for removing global effects in small-animal functional MRI.
AB  - Global effects in functional MRI are temporal modulations in signal intensity
      resulting from various scanner and subject phenomena. These effects contribute to
      the overall variance, reducing the effect size associated with an experimental
      paradigm. Statistical estimations that include an approximation for concurrent
      global effects will reduce the residual error within the model and so improve
      statistical power of the study. Conventionally, estimates of global effects are
      derived from mean intracerebral signal intensities, but these may be prone to
      contributions from localised experimentally evoked signal changes. In such cases,
      inaccurate estimates of global effects may result in erroneous inferences of
      neural modulations based on statistical artefact. A novel, computationally
      simple, method of estimating global effects is proposed using muscle tissue
      acquired within the same acquisition volume. Quantitative improvements in
      sensitivity are reported for a somatosensory stimulation paradigm using global
      muscle signal intensities as a covariate of no-interest. The method is
      independent of local neurogenic signal changes and, under particular experimental
      conditions, may be more representative of true global effects. The utility of
      this strategy to applications in small-animal functional MRI that evoke systemic
      physiological changes as a result of the experimental manipulation is critically
      discussed.

PMID- 17436356
TI  - Duration of therapy with metoclopramide: a prescription claims data study.
AB  - PURPOSE: Metoclopramide-induced tardive dyskinesia is associated with cumulative
      drug exposure, which can result from prolonged use of the drug. We estimated
      therapy duration with metoclopramide, and measured the extent of therapy beyond
      the maximum time period of 12 weeks evaluated in the clinical trials and
      recommended in the label. METHODS: Prescription claims for metoclopramide from
      2002 to 2004 were extracted for participants residing throughout the US and
      contained within the Caremark pharmacy benefit manager (PBM) database. An episode
      of therapy was defined as one or a series of consecutive claims with no more than
      a 30-day lag between the dispensing date of a new claim and the ending date of
      the preceding claim. Episode duration was calculated by subtracting the start
      date from the end date for each episode. RESULTS: During the study period, almost
      80% of participants (total = 200 907) had only one episode of therapy. The length
      of the longest episode for most patients (85%) varied from 1 to 90 days, yet 15%
      of the patients appeared to have received prescriptions for metoclopramide for a
      period longer than 90 days. Cumulative therapy for longer than 90 days was
      recorded for almost 20% of the patients. CONCLUSIONS: These results suggest that
      despite the known risk of tardive dyskinesia and the labeled recommendations on
      duration of metoclopramide use, many patients appear to use the drug for
      relatively long time periods beyond the labeled recommendations. Physicians
      should carefully consider the risk-benefit profile of the drug and, if possible,
      avoid increased risk of tardive dyskinesia due to prolonged exposure.

PMID- 17436357
TI  - The role of academia and the research community in assisting the Food and Drug
      Administration to ensure U.S. drug safety.
AB  - PURPOSE: Academia can play a prominent role in the drug safety arena, unique from
      that of industry, and a clearer articulation of how it could positively influence
      the current system is needed. We sought to examine ways that academia could
      expand its role in U.S. drug safety. METHODS: An ad hoc meeting of academic
      experts in drug safety and risk management was convened at the Institute of
      Medicine (IOM) in Washington, D.C. RESULTS: Academia should develop a stronger
      partnership with the Food and Drug Administration (FDA) to increase research on
      regulatory issues and public health questions and facilitate the prioritization
      of critical issues on drug safety. Such a collaboration could also facilitate the
      development of a network of academic centers of excellence in
      pharmacoepidemiology to address drug safety and risk management questions from a
      public health standpoint in a timely fashion. The development and testing of
      methodologic innovations on drug safety should also be encouraged. CONCLUSIONS:
      Greater partnership between academia and the FDA could facilitate the
      prioritization of important issues on drug safety, allow more research questions
      on drug safety to be answered in a timely fashion, promote the development of
      networks for answering these questions, and help generate additional research
      ideas, ultimately providing enormous benefit to the public health.

PMID- 17436358
TI  - Results of forty years Yellow Card reporting for commonly used perioperative
      analgesic drugs.
AB  - BACKGROUND: A variety of analgesics are used perioperatively and associated
      adverse drug reactions (ADRs) may complicate anaesthesia and recovery. METHODS:
      We aimed to measure the demographics of reported suspected ADRs to alfentanil,
      fentanyl, ketorolac, morphine, nalbuphine, papaveretum, pethidine and
      remifentanil. We report a retrospective analysis of Yellow Card reports of
      suspected ADRs from 1965-2004 as classified in the Adverse Drug Reaction On-line
      Tracking database (ADROIT) of the Medicines and Healthcare products Regulatory
      Agency (MHRA). RESULTS: In total, 1312 reactions were retrieved. A single drug
      was reported in 908, 39 were fatal and 219 categorised as 'allergic'. Allergic
      phenomenon varied from 2/33 (6%) for remifentanil to 11/53 (21%) for alfentanil.
      'Cardiovascular' reactions were reported frequently with remifentanil (18/33,
      55%) and alfentanil (19/53, 36%) and these generated a signal for possible
      hazards from proportional reporting ratios (PRRs). The opioid fentanyl was
      associated with similar hazard signals for muscular and psychiatric ADRs.
      CONCLUSIONS: Perioperative vigilance may reduce morbidity and mortality from
      preventable ADRs to analgesic drugs. Denominator and diagnostic data are
      essential for prospective studies.

PMID- 17436359
TI  - Effects of use of alternative therapies on quality of life and healthcare
      spending.
AB  - Osteoarthritis (OA) is a costly disease that causes much morbidity and mortality
      in the world, and it was the sixth leading cause of disability in developed
      countries. We aim to study the utilization pattern of alternative therapies and
      their effects on quality of life and personal health spending in Chinese OA
      patients in Hong Kong. Five-hundred forty-seven patients with OA from four
      regional hospitals in Hong Kong were recruited, and we measured various types of
      alternative therapies, SF-36 scales, an overall Health Utility Index derived from
      a pre-scored multi-attribute classification system based upon SF-36 health
      surveys, health spending per person and out-of-pocket payments and side-effects.
      The study shows that out of the 547 OA patients, the patients have used a wide
      spectrum of alternative therapies and often used a multiplicity of them. Payment
      for alternative therapies constitutes 5% of the overall personal healthcare
      spending, and 29% of the out-of-pocket payments. The use of alternative therapies
      was significantly associated with higher personal healthcare spending (p = 0.01),
      after adjusting for socioeconomic variables, years of OA and severity of OA. The
      use of alternative therapies was not significantly associated with an improvement
      in the quality of life in the regression analysis (p = 0.64). The use of
      alternative therapies was statistically significant associated with the side
      effects, including gastric discomfort and gastric ulcer/bleeding (p = 0.04, 0.02,
      respectively). Alternative therapies were used extensively by OA patients in Hong
      Kong. Clinicians, health policy makers, and insurance carriers should be aware of
      the potential health and economic effects in practice and policy formulation.

PMID- 17436360
TI  - Xiong-gui-tiao-xue-yin (Kyuki-chouketsu-in), a traditional herbal medicine,
      stimulates lactation with increase in secretion of prolactin but not oxytocin in
      the postpartum period.
AB  - The aim of the present investigation was to evaluate the clinical efficacy of
      Xiong-gui-tiao-xue-yin, a traditional Japanese herbal medicine, in stimulating
      lactation in the postpartum period. We enrolled 82 women who had a normal
      delivery in Osaka Medical College Hospital, and randomly assigned them to the
      following two groups: a group of 41 women who received Xiong-gui-tiao-xue-yin at
      a dose of 6.0 g/day (Group X), and a group of 41 women who received ergometrine
      (methylergometrine maleate) at a dose of 0.375 mg/day (Group E). Volume of
      lactation was determined daily until Day 6 postpartum. Plasma prolactin and
      oxytocin concentration were measured at Days 1 and 6 postpartum. The results
      showed that volume of lactation was significantly higher in Group X than in Group
      E at Days 4 (p = 0.042), 5 (p = 0.038), and 6 (p = 0.046). Significant
      differences between Groups X and E were noted in plasma prolactin concentration
      at Days 1 (157.9 +/- 78.2 ng/ml and 129.1 +/- 64.8 ng/ml; p = 0.037) and 6 (167.5
      +/- 95.4 ng/ml and 117.1 +/- 53.6 ng/ml; p = 0.0042) postpartum. On the other
      hand, at Day 1, oxytocin concentration was significantly higher in Group E than
      in Group X (p = 0.0024). No adverse effects were observed in this study. The
      results of our study demonstrate the beneficial effects of Xiong-gui-tiao-xue-yin
      on lactation, with increase in prolactin level without increase in oxytocin level
      in the postpartum period. Therefore, Xiong-gui-tiao-xue-yin can be expected to
      improve lactation in women in the postpartum period. Further detailed bio
      pharmacological studies and clinical trials to investigate the properties of this
      drug are warranted.

PMID- 17436361
TI  - Effectiveness of combining manual therapy and acupuncture on temporomandibular
      joint dysfunction: a retrospective study.
AB  - This retrospective study investigated the effects of combining manual therapy and
      acupuncture on the pain and maximal mouth opening (MMO), which were associated
      with temporomandibular joint dysfunction (TMD). The 49 TMD patients (15 men, 34
      women; mean age = 30.47 years, SD = 13.52 years) were treated with a combination
      of acupuncture and manual therapy two or three times a week at the hospital. The
      pain and maximal mouth opening were assessed before and after 1 and 4 weeks of
      treatment. The combination therapy produced significant changes in pain levels (p
      < 0.001) and mouth opening (p < 0.001). All pairwise non-parametric comparison
      showed a significant improvement in pain (p < 0.05 for all pairs) and MMO (p <
      0.05 for all pairs). These findings suggest that combining manual therapy and
      acupuncture decreases the pain level and increases the MMO of TMD patients.
      However, future studies should further investigate the efficacy of combined
      treatment on TMD with more rigorous randomized clinical trials.

PMID- 17436362
TI  - Crossover clinical trial to determine the effect of manual acupuncture at Siguan
      points (bilateral LI4 and LR3) on intestinal motility in healthy subjects.
AB  - This study examined whether manual acupuncture at the Siguan points (bilateral
      points LI4 and LR3) affects intestinal motility in healthy human subjects. Twenty
      healthy male subjects were randomly assigned either to real acupuncture (RA) at
      Siguan points or sham acupuncture (SA) groups in a crossover manner. All subjects
      underwent two experimental sessions; the RA group in the first session was
      treated with SA in the second session after a 2-week washout period, and vice
      versa. Each subject took 20 radio-markers and was treated with acupuncture 0, 12,
      24, and 36 hours after radio-marker intake. Radiographs were taken at 6, 12.5,
      24.5, and 48 hours, and the effect of acupuncture on intestinal motility was
      evaluated based on the distribution of the radio-markers in the ileum, ascending
      colon, transverse colon, descending colon, sigmoid/ rectum, and outside the body.
      Defecating habit was monitored during the trial, and complete blood counts were
      checked before and after the two acupuncture sessions. The RA and SA results
      showed extremely similar distributions of the radio-markers in these five regions
      of the alimentary canal and outside the body in radiographs taken at four
      different times, verifying that there was no effect of manual acupuncture at the
      Siguan points on intestinal motility, at least in healthy human subjects.

PMID- 17436363
TI  - Evaluation of scalp and auricular acupuncture on EEG, HRV, and PRV.
AB  - In this study, the EEG, ECG and blood-pressure-pulse recorder were employed to
      evaluate heart rate variability, pulse rate variability, and EEG of 10 adults
      after scalp (experimental test I) at Sishencong scalp acupoint and auricular
      (experimental test II) acupuncture at Shenmen auricular acupoint for about 10
      min. Comparison of the results between the experimental tests and a control with
      no stimulation test showed that both the heart rate and pulse rate were
      decreased, and the blood pressure fell. The high and low frequency power of FFT
      analysis of heart rate was increased and decreased, respectively; indicating that
      the parasympathetic nerves were activated and the sympathetic nerves were
      inhibited. The analysis of the power spectrum of EEG showed that the number of
      low frequency waves was increased after acupuncture stimulation. Therefore,
      acupuncture on either Sishencong or Shenmen might calm the mind, slow down the
      heart rate, and activate the parasympathetic nerves.

PMID- 17436364
TI  - Appearance of human meridian-like structure and acupoints and its time
      correlation by infrared thermal imaging.
AB  - The meridians and acupoints of human bodies at natural condition are investigated
      among 30 healthy volunteers by infrared thermal imaging technique. The results
      give clear evidence of the existence of infrared radiant tracks along human
      meridian courses. The time dependent evolution of the infrared radiant track is
      observed for the first time. The time rhythm of acupoints is also studied. Our
      findings not only support the view that infrared radiant tracks along human
      meridian courses is a normal vital and physiological phenomenon appearing in
      human beings, but also offer a potential method for noninvasive diagnostic by
      studying the physiological function and pathological change of meridians or
      acupoints by means of thermography.

PMID- 17436365
TI  - The effect of oculo-acupuncture on recovery from ethylene glycol-induced acute
      renal injury in dogs.
AB  - The potential recovery effect by oculo-acupuncture (OA) on ethylene glycol
      induced acute renal injury in dogs was investigated. Acute renal damage was
      induced by ingestion of ethylene glycol in six mongrel dogs. The dogs were
      assigned to control (three dogs) and experimental (three dogs) groups. The
      control group did not receive any treatment, while the experimental group was
      treated with oculo-acupuncture at kidney/urinary bladder region plus zhong jiao
      region of the eyes after the induction of renal damage. Serum blood urea nitrogen
      (BUN), creatinine, sodium (Na), chloride (Cl), and potassium (K) were measured in
      both control and experimental groups. The blood RBC and Hb were also examined.
      The serum BUN and creatinine activities in the experimental group were lower than
      those in the control group, the serum Na and Cl had the irregular change in both
      groups, and the blood Hb in the control and experimental group showed decreasing
      tendency. Significant differences were observed on the 3rd and 7th day in BUN,
      7th day in creatinine, 2nd day in Na and Cl, and 7th day in Hb when compared to
      the control group. Whereas, serum K concentration and RBC in the experimental
      group did not change significantly. The recovery findings of the renal injury
      were also observed in the experimental group histopathologically. In conclusion,
      OA therapy (kidney/urinary bladder region plus zhong jiao region) was effective
      for recovery of the renal injury induced by ethylene glycol in dogs.

PMID- 17436366
TI  - Antinociception of heterotopic electro-acupuncture mediated by the dorsolateral
      funiculus.
AB  - We investigated the inhibitory pathways that mediate the antinociceptive effects
      of heterotopic electro-acupuncture (EA) on formalin injection-induced pain in
      rats. EA (2 ms, 10 Hz, 3 mA) was delivered to heterotopic acupoints HT(7) and
      PC(7) for 30 min; this was followed immediately by subcutaneous injection of
      formalin into the left hind paw of rats. Naltrexone (10 mg/kg, i.p.), an opioid
      receptor antagonist, was administered to evaluate the involvement of endogenous
      opioids. The dorsolateral funiculus (DLF), which is a descending pathway that
      inhibits pain, was transected at the ipsilateral T10-11 level of the thoracic
      spinal cord. EA inhibited behavioral responses to formalin injection-induced pain
      and prevented the pain-induced increase in cFos expression in the lumbar spinal
      cord. Pretreatment with naltrexone did not inhibit the antinociceptive effects of
      EA on formalin injection-induced pain. Transection of the DLF ipsilateral to the
      acupuncture site eliminated the antinociceptive effects of EA. These results
      suggest that the antinociceptive effects of heterotopic EA are mediated by the
      DLF and not by endogenous opioids.

PMID- 17436367
TI  - Methanol extract of Sorbus commixta cortex prevents vascular inflammation in rats
      with a high fructose-induced metabolic syndrome.
AB  - Feeding high fructose (Frc) to rats induces a moderate increase in blood
      pressure, which is associated with insulin resistance. The present study was
      designed to evaluate the effect of the methanol extract of Sorbus commixta cortex
      (MSC) on vascular inflammation in a rat model of the metabolic syndrome induced
      by a high Frc-diet. Male Sprague-Dawley rats were divided into 4 groups and
      treated for 7 weeks as follows: 1) control, 2) high Frc-diet group, 3) Frc/MSC1
      group; high Frc-diet group treated with MSC (100 mg/kg/day), and 4) Frc/MSC2
      group; high Frc-diet group treated with MSC (200 mg/kg/day). High Frc-induced
      decreases of the expression level of aortic endothelial nitric oxide synthase
      (ecNOS) while the production of cyclic GMP (cGMP) was restored by treatment with
      MSC. On the contrary, increases of the expression level of endothelin-1 (ET-1) in
      the aorta, the transcription factor, the cytokine related with vascular
      inflammation, and the adhesion molecules were suppressed by MSC treatment.
      Moreover, MSC treatment was shown to lessen the thickening noted in the aortic
      intima and media of the high Frc-diet group. Our findings suggest that MSC may
      have an anti-vascular inflammatory effect on rats with a high Frc-induced
      metabolic syndrome.

PMID- 17436368
TI  - Administration of tauroursodeoxycholic acid (TUDCA) reduces apoptosis following
      myocardial infarction in rat.
AB  - Black bear bile has been used in traditional Chinese medicine to treat liver and
      eye related illnesses for centuries. A major constituent of bile is
      ursodeoxycholic acid (UDCA). Recent analysis of the cellular effects of UDCA and
      its taurine conjugate tauroursodeoxycholic acid (TUDCA) have demonstrated their
      antiapoptotic properties through regulation of Bcl-2 family and survival
      signaling proteins (Bax, Bad, phosphatidylinositol-3-kinase). In this study, we
      tested the hypothesis that TUDCA administered to rats prior to a myocardial
      infarction (MI) would exhibit anti-apoptotic effects and improve cardiac
      function. Prior to ligation of the left anterior descending (LAD) coronary
      artery, TUDCA (50 mg/ml, 400 mg/kg, IV) or PBS was administered to rats. Animals
      were sacrificed 24 hours after ligation for terminal transferase-mediated dUTP
      digoxigenin nick end-labeling (TUNEL) and caspase-3 activity to assess apoptosis.
      Additional TUDCA or PBS treated rats underwent pre-operative,1 and 4 week
      transthoracic ultrasounds to assess heart function by quantification of
      shortening fraction (SF) and infarct area. TUNEL labeling of the cardiac tissue
      revealed a significant reduction in apoptotic cells in rats given TUDCA prior to
      ischemic injury (p = 0.05). In support of reducing apoptosis, caspase-3 activity
      in the TUDCA treated animals also decreased (p = 0.02). By 4 weeks, a
      significantly smaller infarct area was present in the TUDCA group compared to the
      PBS group (0.05 vs. 0.13 cm(2), p = NS) and there was also an improvement in SF.
      The results provide evidence for TUDCA as a viable treatment for reducing
      apoptosis in a model of myocardial infarction. Additional studies will
      distinguish the functional result of improved cell survival following infarction,
      suggesting the potential for clinical application of this anti-apoptotic drug in
      treatment of acute MI.

PMID- 17436369
TI  - The water extract of adlay seed (Coix lachrymajobi var. mayuen) exhibits anti
      obesity effects through neuroendocrine modulation.
AB  - To find out whether the immunohistochemical expression of neuropeptid Y (NPY) and
      leptin receptor (LR) in the rat hypothalamus is influenced by adlay seed water
      extract (adlay), obesity in rats was induced by high fat diet (HFD) for 8 weeks;
      these rats were injected with 50 mg/100 g body weight adlay daily for 4 weeks.
      The results showed that the optical density of NPY immunoreactivity in
      paraventricular nucleus of rats increased approximately by 3.4 fold in HFD group
      compared to the normal diet group. Conversely, that of HFD + adlay group was
      about 2.6 fold lower than HFD group. The pattern of LR expression was similar to
      that of NPY. Both of NPY and LR mRNA levels, determined by real time PCR, in HFD
      + adlay group were decreased compared to those of HFD group, but there were no
      significant changes in the level of LR. These results suggest that adlay may
      regulate neuroendocrine activity in the brain. Accordingly, administration of
      adlay may be considered for therapies targeting obesity.

PMID- 17436370
TI  - Effects of Tribuli saponins on ventricular remodeling after myocardial infarction
      in hyperlipidemic rats.
AB  - This experiment was designed to determine whether Tribuli saponins (TS) relieve
      left ventricular remodeling (VR) after myocardial infarction (MI) in a murine
      hyperlipemia (HL) model. MI and HL models were induced and high and low doses of
      TS and simvastatin were administrated to the rats. Four weeks later,
      echocardiographic observation was performed and the left and right ventricular
      weight index (LVWI, RVWI) was calculated. Echocardiographic results showed that
      both high dose of TS and simvastatin had a beneficial effect on increasing
      fractional shortening (FS) and ejection fraction (EF), reducing left ventricular
      end diastolic volume (LVEDV), systolic volume (LVESV), left ventricular dimension
      end diastole (LVDd) and systole (LVDs), and decreasing LVWI, as compared to those
      in the HL-MI model group (p < 0.05, 0.01). Both medicines had little impact on
      thickness of the anterior and posterior wall. No significant difference was
      observed between each treatment group (p > 0.05). In conclusion, TS not only
      lowered serum lipidemia, but also relieved left ventricular remodeling, and
      improved cardiac function in the early stage after MI.

PMID- 17436371
TI  - In vivo and in vitro anti-inflammatory activities of neoandrographolide.
AB  - Neoandrographolide, one of the principal diterpene lactones, isolated from a
      medicinal herb Andrographis paniculata Nees, was tested in vivo and in vitro for
      its anti-inflammatory activities and mechanism. Oral administration of
      neoandrographolide (150 mg/kg) significantly suppressed ear edema induced by
      dimethyl benzene in mice. Oral administration of neoandrographolide (100-150
      mg/kg) also reduced the increase in vascular permeability induced by acetic acid
      in mice. In vitro studies were performed using the macrophage cell line RAW264.7
      to study the effect of neoandrographolide on suppressing phorbol-12-myristate-13
      acetate (PMA)-stimulated respiratory bursts and lipopolysaccharide (LPS)-induced
      production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha).
      Respiratory bursts were quantified by chemiluminescence (CL) measurements.
      Results showed that neoandrographolide suppressed PMA-stimulated respiratory
      bursts dose-dependently from 30 muM to 150 muM. Neoandrographolide also inhibited
      NO and TNF-alpha production in LPS-induced macrophages, contributing to the anti
      inflammatory activity of A. paniculata. These results indicate that
      neoandrographolide possesses significant anti-inflammatory effects, which implies
      that it would be one of the major contributing components to participate in the
      anti-inflammatory effect of A. paniculata. and a potential candidate for further
      clinical trial.

PMID- 17436372
TI  - Transgenic Panax ginseng inhibits the production of TNF-alpha, IL-6, and IL-8 as
      well as COX-2 expression in human mast cells.
AB  - The most well-known medicinal plant, Panax ginseng (P. ginseng), contains various
      phytosterols and bioactive triterpene saponins (ginsenosides). Squalene synthase
      is a key regulatory enzyme for triterpene biosynthesis and overexpression of the
      squalene synthase confers the hyper-production of triterpene saponins to form
      transgenic ginseng. In this study, we have investigated whether and how
      transgenic P. ginseng modulates an inflammatory reaction in a stimulated human
      mast cell line, HMC-1. It was found that transgenic P. ginseng inhibited the
      production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and
      the expression of cyclooxygenase-2 in phorbol 12-myristate 13-acetate (PMA) plus
      calcium ionophore A23187 (PMACI)-stimulated HMC-1. Additionally, we have shown
      that transgenic P. ginseng suppressed the intracellular calcium level induced by
      PMACI. These results provide new insights into the pharmacological actions of
      transgenic P. ginseng as a potential molecule for use in therapy in mast cell
      mediated inflammatory diseases.

PMID- 17436373
TI  - Sho-saiko-to (Xiao-Chai-Hu-Tang) and crude saikosaponins inhibit hepatitis B
      virus in a stable HBV-producing cell line.
AB  - To search for an effective antiviral agent, this study tested the hypothesis that
      sho-saiko-to (Xiao-Chai-Hu-Tang) and crude saikosaponins possess the activity
      directly against HBV and could affect the expressions of viral antigens, HBeAg
      and HBsAg, in HepG(2) 2.2.15 cell model. The viral amount and viral antigens in
      the suspension were estimated by quantitative real time PCR and enzyme-linked
      immunosorbent assay (ELISA), respectively. The results showed that sho-saiko-to
      could inhibit the production of HBV (p < 0.0001), 20 microg/ml sho-saiko-to was
      efficacious at day-3 of treatment and 10 microg/ml at day-6. The calculated
      IC(50) and CC(50) of sho-saiko-to were 55.76 microg/ml and 372 microg/ml,
      respectively, with a selectivity index of 6.67. Crude saponin of B. chinense
      could also inhibit the replication of HBV (p < 0.0001). Owing to the anti
      neoplastic activity of sho-saiko-to and saikosaponin, their calculated CC(50) and
      selectivity index might be under-estimated. Sho-saiko-to also decreased the
      expression of HBeAg with the minimal effective concentration of 20 microg/ml. Sho
      saiko-to contained too little saikosaponin. Therefore, the anti-HBV activity of
      sho-saiko-to might not be mediated by saikosaponin. Sho-saiko-to could be
      supplementary to nucleotide analogues to minimize the recurrence of viremia after
      its discontinuation.

PMID- 17436374
TI  - Compositions and biological activities of essential oils of Kadsura
      longepedunculata and Schisandra sphenanthera.
AB  - The chemical compositions, antimicrobial activities, antioxidant activities and
      cytotoxicities of the essential oils isolated from the root of Kadsura
      longepedunculata Finet et Gagnep (KLREO) and the fruit of Schisandra sphenanthera
      Rehd. et Wills. (SSFEO) were investigated.The analyses of gas chromatography-mass
      spectrometry (GC-MS) showed that cadinane type compounds and their derivatives
      were rich in both oils (54.2% and 39.7%, respectively) and delta-cadinene was the
      major component of both oils (13.8% and 25.6%, respectively). The antimicrobial
      activities of both oils were evaluated against five microorganisms with the disc
      diffusion and the broth micro-dilution method. Results showed that Gram-positive
      bacteria were more sensitive to both oils than Gram-negative bacteria and the
      yeast. The minimum inhibitory concentration (MIC) and minimum bactericidal
      concentration (MBC) of the oil of KLREO were lower than those of SSFEO,
      indicating that the former possessed slightly stronger antibacterial capability
      than the latter. The reducing power and lipid peroxidation assays were employed
      to study the potential antioxidant activities of both oils. Both oils remarkably
      decreased the content of malondialdehyde (MDA) in rat liver homogenate in a dose
      dependent manner. The antioxidant activities of KLREO appeared to be more potent
      than that of SSFEO. The oils of KLREO and SSFEO exhibited concentration-dependent
      cytotoxicities and were proved to be toxic to HepG2 cells with IC(50) of 147 and
      189 mug/ml, respectively.

PMID- 17436375
TI  - Comment on "Birdcage model for the Chinese meridian system".

PMID- 17436377
TI  - Heterogeneity of posttraumatic stress disorder symptoms in Croatian war veterans:
      retrospective study.
AB  - AIM: To determine the relationship between the intensity of combat-related
      posttraumatic stress disorder (PTSD) and the intensity of predominating symptoms.
      METHOD: The study included 151 veterans from 1992-1995 war in Croatia (aged
      38.3+/-7.3 years) with PTSD. The veterans were psychologically tested with the
      Mississippi Scale for Combat-related PTSD (M-PTSD), Questionnaire on Traumatic
      Combat and War Experiences (USTBI-M), and Minnesota Multiphasic Personality
      Inventory-version 201 (MMPI-201). RESULTS: The discriminative analysis of the
      data revealed that the group with lower PTSD intensity had the highest scores on
      MMPI scales D (depression, T-score 98.3+/-5.6), Hs (hypochondriasis, 90.1+/-5.1),
      and Hy (hysteria, 89.5+/-4.9), whereas the group with higher PTSD intensity,
      besides these three scales (D=95.7+/-5.3; Hs=87.6+/-4.3; Hy=85.6+/-4.7), also had
      clinically significantly elevated Pt (psychastenia, 80.6+/-5.6), Sc
      (schizophrenia, 79.6+/-4.8), and Pa (paranoia, 85.6+/-5.4) scales, with the
      highest Pa scale. CONCLUSION: It was possible to differentiate study participants
      with different PTSD intensity on the basis of their MMPI profile. More intense
      PTSD was associated with externalized symptoms, such as aggression, acting-out,
      hostility, and mistrust, whereas less intensive PTSD was associated with mostly
      depressive symptoms. Our study showed that different intensity of PTSD has
      different symptom patterns.

PMID- 17436378
TI  - Short-term memory in Croatian war veterans with posttraumatic stress disorder.
AB  - AIM: To assess short-term memory impairment in war veterans with combat-related
      posttraumatic stress disorder (PTSD). METHOD: The study included 20 war veterans
      diagnosed with PTSD and 21 control subjects matched for age, sex, and education
      level. Both groups were tested with the Rey-Osterrieth Complex Figure Test
      (ROCFT), consisting of Copy, Immediate Recall, and Delayed Recall steps, and
      Benton Visual Retention Test (BVRT). Subjects with visuoperceptive and
      visuoconstructional deficits, as indicated by their ROCFT Copy scores were
      excluded from the analysis, because this type of cognitive deficit could
      interfere with the results of the next two ROCFT steps measuring short-term
      memory. RESULTS: Subjects with PTSD scored significantly lower than control
      subjects on both Immediate Recall (mean+/-standard deviation [SD], 16.3+/-6.4 vs
      26.7+/-4.5, respectively; P<0.001, t-test for independent samples) and Delayed
      Recall tests (15.7+/-6.1 vs 26.3+/-4.6, respectively; P<0.001, t-test for
      independent samples) on ROCFT test. Intragroup comparison showed that both groups
      scored significantly lower on Immediate Recall test in comparison with Copy test
      (19.3+/-6.4 for veterans and 8.9+/-4.5 for controls; P<0.001 for both, t-test for
      dependent samples), whereas no significant score difference was found between
      Immediate and Delayed Recall scores in either group (0.7+/-2.4 for veterans,
      P=0.239, t-test for dependent samples; and 0.5+/-1.8 for controls, P=0.248, t
      test for dependent samples), which indicated greater difficulties with acquiring
      new information than with recalling already memorized information. Subjects with
      PTSD made significantly more errors on the BVRT for visuoperceptive and
      visuoconstructional abilities than control subjects (7.8+/-2.9 for veterans;
      4.0+/-1.88 for controls; P<0.001, t-test for independent samples). CONCLUSION:
      War veterans with PTSD had impaired short-term memory and visual retention, but
      these cognitive deficits could not be related to traumatic experiences with
      certainty.

PMID- 17436380
TI  - Treatment outcomes and perception of social acknowledgment in war veterans:
      follow-up study.
AB  - AIM: To assess treatment outcomes of psychotherapy for war veterans suffering
      from posttraumatic stress disorder (PTSD) and to investigate self-perceived
      social acknowledgment. METHODS: In this prospective cohort study, a set of
      psychological instruments was used to assess the level of posttraumatic stress
      symptoms (Clinician-Administered PTSD Scale, Impact of Event Scale--Revised),
      symptoms of general psychopathology (Brief Symptom Inventory), quality of life
      (The Manchester Short Assessment of Quality of Life), and perceived social
      acknowledgment on a sample of 152 Croatian war veterans participating in group
      psychotherapy. All participants were interviewed at baseline and followed up
      after 3 and 12 months. We analyzed the changes in symptom levels over the course
      of one year, as well as the correlations between symptoms (both at baseline and
      after therapy) and perceived social acknowledgment. RESULTS: The analysis of
      symptom levels at the beginning of group therapy and after 12 months showed
      minimal or no changes in their intensity. Only the symptoms of intrusion (ANOVA,
      F-value=7.09, P<0.001) were significantly reduced after a period of 12 months.
      Levels of hostility (ANOVA, F-value=7.85, P<0.001) and psychoticism were
      significantly increased (ANOVA, F-value=7.80, P<0.001) at the end of the
      treatment. Other categories of posttraumatic symptoms and the level of general
      psychopathology did not change significantly during the course of treatment. The
      results showed that war veterans perceive extremely low levels of social
      acknowledgment, especially from their wider social environment: 92.9% perceived a
      lack of acknowledgment from governmental institutions and 95.4% from the state in
      general. CONCLUSION: Despite some methodological constraints, our results showed
      that even 10 years after the traumatization, PTSD symptoms among war veterans
      remained intense and that undergoing therapy over a year did not produce
      significant improvements, except on the dimension of intrusion. Veterans were
      highly sensitive to the way their primary social environment and the society as a
      whole react to their problems.

PMID- 17436379
TI  - Psychiatric heredity and posttraumatic stress disorder: survey study of war
      veterans.
AB  - AIM: To explore the prevalence of psychiatric heredity (family history of
      psychiatric illness, alcohol dependence disorder, and suicidality) and its
      association with the diagnosis of stress-related disorders in Croatian war
      veterans established during psychiatric examination. METHODS: The study included
      415 war veterans who were psychiatrically assessed and diagnosed by the same
      psychiatrist during an expert examination conducted for the purposes of
      compensation seeking. Data were collected by a structured diagnostic procedure.
      RESULTS: There was no significant correlation between psychiatric heredity of
      psychiatric illness, alcohol dependence, or suicidality and diagnosis of
      posttraumatic stress disorder (PTSD) or PTSD with psychiatric comorbidity.
      Diagnoses of psychosis or psychosis with comorbidity significantly correlated
      with psychiatric heredity (Phi=0.111; P=0.023). There was a statistically
      significant correlation between maternal psychiatric illness and the patients'
      diagnoses of partial PTSD or partial PTSD with comorbidity (Phi=0.104; P=0.035)
      and psychosis or psychosis with comorbidity (Phi=0.113; P=0.022); paternal
      psychiatric illness and the patients' diagnoses of psychosis or psychosis with
      comorbidity (Phi=0.130; P=0.008), alcohol dependence or alcohol dependence with
      comorbidity (Phi=0.166; P=0.001); psychiatric illness in the primary family with
      the patients' psychosis or psychosis with comorbidity (Phi=0.115; P=0.019);
      alcohol dependence in the primary family with the patients' personality disorder
      or personality disorder with comorbidity (Phi=0.099; P=0.044); and suicidality in
      the primary family and a diagnosis of personality disorder or personality
      disorder with comorbidity (Phi=0.128; P=0.009). CONCLUSION: The study confirmed
      that parental and familial positive history of psychiatric disorders puts the
      individual at higher risk for developing psychiatric illness or alcohol or drug
      dependence disorder. Psychiatric heredity might not be necessary for the
      individual who was exposed to severe combat-related events to develop symptoms of
      PTSD.

PMID- 17436381
TI  - Psychological consequences of war trauma and postwar social stressors in women in
      Bosnia and Herzegovina.
AB  - AIM: To assess the consequences of psychotrauma in civilian women in Herzegovina
      who were exposed to prolonged and repetitive traumatic war events and postwar
      social stressors. METHODS: The study included a cluster sample of 367 adult
      women, divided into two groups. One group (n=187) comprised women from West
      Mostar who were exposed to serious war and posttraumatic war events. The other
      group (n=180) comprised women from urban areas in Western Herzegovina who were
      not directly exposed to war destruction and material losses, but experienced war
      indirectly, through military drafting of their family members and friends.
      Demographic data on the women were collected by a questionnaire created for the
      purpose of this study. Data on trauma exposure and posttraumatic stress disorder
      (PTSD) symptoms were collected by Harvard Trauma Questionnaire (HTQ)--Bosnia
      Herzegovina version. General psychological symptoms were determined with Symptom
      Check List-90-revised (SCL-90-R). Data on postwar stressors were collected by a
      separate questionnaire. RESULTS: In comparison with the control group, women from
      Western Mostar experienced significantly more traumatic events (mean+/-standard
      deviation [SD], 3.3+/-3.2 vs 10.1+/-4.9, respectively, t=15.91; P<0.001) and had
      more posttraumatic symptoms (12.3+/-10.3 vs 21.2+/-10.9, respectively, t=8.42;
      P<0.001). They also had significantly higher prevalence of PTSD (4.4% vs 28.3%,
      respectively; chi(2)=52.56; P<0.001). The number of traumatic events experienced
      during the war was positively associated with postwar stressful events both in
      the West Mostar group (r=0.223; P=0.002) and control group (r=0.276; P<0.001).
      Postwar stressful events contributed both to the number and intensity of PTSD
      symptoms and all general psychological symptoms measured with SCL-90
      questionnaire, independently from the number of experienced traumatic war events.
      CONCLUSION: Long-term exposure to war and postwar stressors caused serious
      psychological consequences in civilian women, with PTSD being only one of the
      disorders in the wide spectrum of posttraumatic reactions. Postwar stressors did
      not influence the prevalence of PTSD but they did contribute to the intensity and
      number of posttraumatic symptoms.

PMID- 17436382
TI  - Secondary traumatization of wives of war veterans with posttraumatic stress
      disorder.
AB  - AIM: To determine the symptoms of secondary traumatic stress and possible
      influences of demographic and socioeconomic factors on the occurrence of
      secondary traumatic stress in wives of war veterans with posttraumatic stress
      disorder (PTSD). METHOD: The study included 56 wives of war veterans diagnosed
      with PTSD and treated at the Center for Psychotrauma in Rijeka, Croatia. A short
      structured interview was conducted with each woman to collect demographic and
      socioeconomic data. The women independently completed an adapted 16-item version
      of Indirect Traumatization Questionnaire to determine the presence of secondary
      traumatic stress symptoms, which corresponded with PTSD symptoms as defined by
      the fourth edition of the Diagnostic and Statistical Manual for Mental Disorders.
      RESULTS: Out of 56 veterans' wives included in the study, 32 had six or more
      symptoms of secondary traumatic stress, whereas only 3 had none of the symptoms.
      Twenty-two women met the diagnostic criteria for secondary traumatic stress.
      Women with secondary traumatic stress were married longer than those without it
      (mean+/-standard deviation, 19.1+/-9.1 vs 13.2+/-7.8 years, respectively;
      P=0.016). Eleven of 22 women with secondary traumatic stress and 8 of 34 women
      without secondary traumatic stress were unemployed (P=0.05). CONCLUSION: As more
      than a third of war veterans wives met the criteria for secondary traumatic
      stress, any treatment offered to veterans with PTSD must address the
      traumatization of their family.

PMID- 17436383
TI  - Posttraumatic stress disorder: diagnostic data analysis by data mining
      methodology.
AB  - AIM: To use data mining methods in assessing diagnostic symptoms in posttraumatic
      stress disorder (PTSD). METHODS. The study included 102 inpatients: 51 with a
      diagnosis of PTSD and 51 with psychiatric diagnoses other than PTSD. Several
      models for predicting diagnosis were built using the random forest classifier,
      one of the intelligent data analysis methods. The first prediction model was
      based on a structured psychiatric interview, the second on psychiatric scales
      (Clinician-administered PTSD Scale--CAPS, Positive and Negative Syndrome Scale-
      PANSS, Hamilton Anxiety Scale--HAMA, and Hamilton Depression Scale--HAMD), and
      the third on combined data from both sources. Additional models placing more
      weight on one of the classes (PTSD or non-PTSD) were trained, and prototypes
      representing subgroups in the classes constructed. RESULTS: The first model was
      the most relevant for distinguishing PTSD diagnosis from comorbid diagnoses such
      as neurotic, stress-related, and somatoform disorders. The second model pointed
      out the scores obtained on the CAPS scale and additional PANSS scales, together
      with comorbid diagnoses of neurotic, stress-related, and somatoform disorders as
      most relevant. In the third model, psychiatric scales and the same group of
      comorbid diagnoses were found to be most relevant. Specialized models placing
      more weight on either the PTSD or non-PTSD class were able to better predict
      their targeted diagnoses at some expense of overall accuracy. Class subgroup
      prototypes mainly differed in values achieved on psychiatric scales and frequency
      of comorbid diagnoses. CONCLUSION: Our work demonstrated the applicability of
      data mining methods for the analysis of structured psychiatric data for PTSD. In
      all models, the group of comorbid diagnoses, including neurotic, stress-related,
      and somatoform disorders, surfaced as important. The important attributes of the
      data, based on the structured psychiatric interview, were the current symptoms
      and conditions such as presence and degree of disability, hospitalizations, and
      duration of military service during the war, while CAPS total scores, symptoms of
      increased arousal, and PANSS additional criteria scores were indicated as
      relevant from the psychiatric symptom scales.

PMID- 17436384
TI  - Circulating lymphocyte subsets, natural killer cell cytotoxicity, and components
      of hypothalamic-pituitary-adrenal axis in Croatian war veterans with
      posttraumatic stress disorder: cross-sectional study.
AB  - AIM: To determine peripheral blood lymphocyte subsets--T cells, helper T cells,
      cytotoxic T cells, B cells, and natural killer cells, natural killer cell
      cytotoxicity, serum cortisol concentration, and lymphocyte glucocorticoid
      receptor expression in Croatian combat veterans diagnosed with chronic
      posttraumatic stress disorder (PTSD); and to examine the relationship between the
      assessed parameters and the time passed since the traumatic experience. METHODS:
      Well-characterized group of 38 PTSD patients was compared to a group of 24
      healthy civilians. Simultaneous determination of lymphocyte subsets and the
      expression of intracellular glucocorticoid receptor was performed using three
      color flow cytometry. Natural killer cell cytotoxicity was measured by (51)Cr
      release assay and the serum cortisol concentration was determined by
      radioimmunoassay. RESULTS: We found higher lymphocyte counts in PTSD patients
      than in healthy controls (2294.7+/-678.0/microL vs 1817.2+/-637.0/microL,
      P=0.007) and a positive correlation between lymphocyte glucocorticoid receptor
      expression and the number of years that passed from the traumatic experience
      (r(s)=0.43, P=0.008). Lymphocyte glucocorticoid receptor expression positively
      correlated with serum cortisol concentration both in PTSD patients (r=0.46,
      P=0.006) and healthy controls (r=0.46, P=0.035). CONCLUSION: This study confirmed
      that the immune system was affected in the course of chronic PTSD. Our findings
      also indicated that the hypothalamic-pituitary-adrenal axis profile in PTSD was
      associated with the duration of the disorder. Due to the lack of power, greater
      sample sizes are needed to confirm the results of this study.

PMID- 17436385
TI  - Significance of genetic abnormalities of p53 protein in Slovenian patients with
      gastric carcinoma.
AB  - AIM: To analyze genetic alterations of p53 gene in Slovenian gastric cancer
      patients and to compare these alterations with clinicopathological parameters in
      order to assess the value of p53 as a prognostic factor. METHODS: We analyzed the
      samples from 230 Slovenian patients with gastric cancer, collected between 1983
      and 2001. p53 expression was evaluated immunohistochemically with DO-7 monoclonal
      antibody. In addition, loss of heterozigosity (LOH) and microsatellite
      instability (MSI) of p53 gene were evaluated, as well as its mutational status in
      the selected population of patients. RESULTS: p53 expression was associated with
      poorer survival and it was an independent predictor in multivariate analysis,
      along with TNM (T--size of tumor, N--nodal involvement, M--distant metastasis)
      stage status. Loss of heterozigosity and microsatellite instability status did
      not influence survival, however we found association of loss of heterozigosity
      with Lauren's (Mantel-Haenszel test, P=0.004) and Ming's (Mantel-Haenszel test,
      P<0.001) classification, whereas microsatellite instability was associated with
      gender (Mantel-Haenszel test, P=0.017), TNM stage (chi(2) test, P=0.006) of
      gastric cancer, and lymph node involvement (pN) (chi(2) test, P=0.004).
      Conclusions. The data on p53 abnormalities, when considered separately, could be
      of relative value for predicting the behavior of gastric tumors. However, our
      analyses showed that studying p53 overexpression, loss of heterozigosity,
      microsatellite instability, and mutational analysis could provide data that,
      particularly in combination with some clinicopathological features, might be of
      clinical value for predicting the tumor behavior and patient response to therapy.

PMID- 17436386
TI  - K-ras and Dpc4 mutations in chronic pancreatitis: case series.
AB  - AIM: To assess whether alterations in the K-ras, p53, and DPC4 genes are present
      in pancreatitis, a potential precancerous condition that can progress to
      pancreatic adenocarcinoma. To investigate the alterations occurring at hot spots
      of K-ras (exon 1), p53 (exons 5 and 7), and DPC4 (exons 8, 10 and 11). METHODS:
      In 10 patients with acute and 22 with chronic pancreatitis, without pancreatic
      intraepithelial neoplasia (PanIN), DNA was isolated from paraffin embedded tissue
      samples. The extracted DNA was analyzed by polymerase chain reaction (PCR),
      restriction fragment length polymorphism (RFLP) analysis, single-strand
      conformation polymorphism (SSCP) analysis, and DNA sequencing. RESULTS: In acute
      pancreatitis samples no mutations were found in any of the investigated genes. In
      7 out of 22 samples of chronic pancreatitis nucleotide substitution at exon 1 of
      K-ras (five at codon 12 and two at codon 13) were found. No mutations in p53
      (exons 5 and 7) were detected. Two samples had nucleotide substitutions at exons
      8 and 11 of DPC4, introducing STOP signal and change in the amino acid sequence,
      respectively. One chronic pancreatitis sample displayed simultaneous mutations in
      K-ras (exon 1, codon 12) and DPC4 (exon 8, codon 358). CONCLUSION: Mutations of K
      ras and Dpc4 genes can accumulate already in non-malignant, inflammatory
      pancreatic tissue, suggesting its applicability in monitoring of further
      destruction of pancreatic tissue and progression into malignancy.

PMID- 17436387
TI  - Conventional risk factors and acute coronary syndrome during a period of
      socioeconomic transition: population-based case-control study in Tirana, Albania.
AB  - AIM: To assess the association between conventional risk factors and acute
      coronary syndrome in Albania, a transitional country in Southeast Europe.
      METHODS: A population-based case-control study was conducted in Tirana in 2003
      2006. A total of 467 consecutive patients with nonfatal acute coronary syndrome
      were recruited. There were 370 men with mean+/-standard deviation (SD) age of
      59.1+/-8.7 years and 97 women with mean+/-SD age of 63.3+/-7.1 years. The control
      group comprised a population-representative sample of Tirana residents. In the
      control group, there were 469 men with mean+/-SD age of 53.1+/-10.4 years and 268
      women aged 54.0+/-10.9 years. A structured questionnaire on demographic,
      socioeconomic, psychosocial factors, and health behaviors was administered.
      Physical measurements included anthropometrics and blood pressure. Venous blood
      and adipose tissue aspirations from the gluteal region were frozen-stored for
      future analysis. Multivariable-adjusted logistic regression was used to assess
      the independent associations of conventional risk factors with acute coronary
      syndrome. RESULTS: Upon adjustment for covariates, family history of coronary
      heart disease was found to be a strong predictor of acute coronary syndrome in
      both men (odds ratio [OR], 3.70; 95% confidence interval [CI], 2.58-5.30) and
      women (OR, 4.53; 2.40-8.57). Waist-to-hip ratio in men (OR, 4.03; 2.83-5.73) and
      obesity in women (OR, 3.31; 1.54-7.14) were strongly associated with acute
      coronary syndrome. In men, but not in women, there was a significant association
      with hypertension and current smoking (P=0.011 and P<0.001, respectively).
      Diabetes was not significantly independently associated in either sex.
      CONCLUSION: Classical risk factors predicted coronary heart disease in Albania,
      similarly as in the rest of the world, although associations with family history
      and anthropometric indices were stronger. These findings are resulting largely
      from the heterogeneous adoption of lifestyles conducive to increased coronary
      risk in transitional countries, and they point to the urgent need for targeted
      public health interventions.

PMID- 17436388
TI  - Efficacy and safety of nebulized recombinant human DNase as rescue treatment for
      persistent atelectasis in newborns: case-series.
AB  - AIM: To evaluate the efficacy and safety of using recombinant human DNase
      (rhDNase) in diminishing persistent atelectasis unresponsive to conventional
      treatment and mucus plugging in newborns with insufficient ability to clear thick
      and purulent airway secretions. METHODS: Twelve newborns (10 preterms), who did
      not respond to conventional methods, received rhDNase nebulized therapy at a dose
      of 1.25 mg over a 15-minute period, twice a day (2 hours between the doses) for
      up to 3 days. The application of the drug was continued for up to 3 days or until
      the improvement of atelectasis. After a-three-day therapy, if atelectasis did not
      improve, a single dose (1.25 mg) of the same drug in liquid form was administered
      endotracheally. Clinical (respiration rate, requirement for oxygen concentration)
      and radiological response (chest x-ray scoring), duration of the treatment,
      recurrence of atelectasis and requirement for additional therapy were evaluated.
      RESULTS: Ten out of 12 patients showed rapid clinical and radiological
      improvement after nebulized treatment. Two patients who did not respond to the
      three-day regimen received a single dose of the drug endotracheally and both
      recovered completely. Six patients did not require completion of three day
      regimen for radiological recovery. Chest x-ray scores and respiratory parameters
      showed significant improvement after the treatment. The respective median (range)
      values before and after treatment were 4 (1-5) and 0 (0-4) points for chest x-ray
      scores, 66 (60-78) and 49 (44-64) breaths/min for respiratory rates, and 45% (35
      64) and 30% (21-40) for oxygen requirement. Comparison of pCO(2) before (median,
      56 mm Hg; range, 46-64) and after treatment (median, 41 mm Hg; range 38-58) in 7
      patients showed significant improvement. CONCLUSION: In a large series of
      newborns to receive rhDNase and we demonstrated the usefulness of rhDNase as a
      mucolytic agent in treating newborns with persistent atelectasis who do not
      respond to other treatments.

PMID- 17436389
TI  - Emotional and physical abuse in family: survey among high school adolescents.
AB  - AIM: To determine the prevalence of different forms of child abuse among high
      school pupils in Slavonski Brod, Croatia. METHOD: The study included 2140 first
      and fourth-grade pupils aged between 14 and 18 years from all 10 high schools in
      Slavonski Brod and the area (4 grammar and 6 vocational schools). The pupils were
      asked to complete an anonymous structured questionnaire during a 45-minute class.
      The questionnaire, developed for the needs of this study, collected basic
      demographic data on family life and experience of emotional or physical abuse.
      RESULTS: First-grade pupils were more satisfied with their family life than
      fourth-grade pupils (96.9% vs 91.3%, P<0.001, chi(2) test). The feeling of being
      insufficiently loved or unloved was reported by 17.5% of the first-grade and
      24.6% of the fourth-grade pupils and a greater percentage of pupils whose parents
      were divorced or who had a step-parent. Almost 80% of pupils had been verbally or
      nonverbally punished for disobedience. Emotional abuse was significantly
      associated with female sex (Nagelkerke R(2)=0.87, beta=0.474, P=0.028), younger
      age (beta=1.263, P<0.001), and alcoholism in the family (beta=2.037, P<0.001.
      Physical punishment for disobedience was reported significantly more often by
      first-grade than fourth-grade pupils (15.6% vs 12.9% P=0.021, chi(2) test).
      Physical abuse was significantly associated (Nagelkerke R2=0.69) with younger age
      (Beta=0.379, P<0.012), emotional abuse (Beta=0.665, P<0.002), alcoholism in the
      family (Beta=1.791, P<0.001) and the lack of parental love (Beta=-0.645,
      P<0.001). Possible sexual molestation was admitted by 6.0% boys and 3.3% girls.
      CONCLUSION: Most high school pupils in Slavonski Brod were satisfied with their
      life at home. Disobedience was usually punished verbally or by aggressive
      behavior of the parents. Physical punishment was less common and usually did not
      result in serious injuries.

PMID- 17436390
TI  - Quality control of epidemiological lectures online: scientific evaluation of peer
      review.
AB  - AIM: To examine the feasibility of using peer review for the quality control of
      online materials. METHODS: We analyzed the inter-rater agreement on the quality
      of epidemiological lectures online, based on the Global Health Network
      Supercourse lecture library. We examined the agreement among reviewers by looking
      at kappa statistics and intraclass correlations. Seven expert reviewers examined
      and rated a random sample of 100 Supercourse lectures. Their reviews were
      compared with the reviews of the lay Supercourse reviewers. RESULTS: Both expert
      and non-expert reviewers rated lectures very highly, with a mean overall score of
      4 out of 5. Kappa (Kappa) statistic and intraclass correlations indicated that
      inter-rater agreement for experts and non-experts was surprisingly low (below
      0.4). CONCLUSIONS: To our knowledge, this was the first time that poor inter
      rater agreement was demonstrated for the Internet lectures. Future research
      studies need to evaluate the alternatives to the peer review system, especially
      for online materials.

PMID- 17436391
TI  - Learning how to speak.

PMID- 17436392
TI  - What drives health research in a developing country?

PMID- 17436393
TI  - Taxonomy: what's in a name? Doesn't a rose by any other name smell as sweet?

PMID- 17436395
TI  - The critical recommendation for the treatment of melanoma patients: primum nil
      nocere.

PMID- 17436396
TI  - Interventional pulmonology techniques for immediate desobstruction of malignant
      central airway obstruction.
AB  - In recent years interventional pulmonology techniques have found their place in
      the palliative treatment of lung cancer invading central airways (trachea and
      principal bronchi). The curative effect of interventional techniques is reported
      in a number of studies with very different success ratios, but with excellent
      potential and perspective. Increase in number and variety of these techniques led
      to the development of internationally accepted guidelines for their use. The
      choice of a specific interventional technique in the treatment of lung cancer
      patients with central airway obstruction (CAO) depends on several factors:
      patient's general condition and comorbidities, type and characteristics of airway
      stenosis, availability of techniques and trained personnel. The aim of this
      review was to introduce interventional pulmonology procedures aimed at urgent
      desobstruction of central airways obstruction to medical oncologists who are
      dealing with the problem of malignant CAO. We tried to emphasize indications,
      contraindications, technique procedure and possible complications in the
      treatment of malignant CAO. At the Institute for Pulmonary Diseases of Vojvodina
      Nd: YAG laser resection, electrocautery, argon plasma coagulation and metallic
      and silicone stent insertions for immediate treatment of malignant CAO are
      practised.

PMID- 17436397
TI  - Is local excision and chemoradiation an acceptable alternative in the treatment
      of early rectal cancer?
AB  - Local excision has a limited but important role in the modern management of
      patients with rectal tumors. The main criticism of the local treatment of early
      rectal cancer (T1N0M0 or T2N0M0) is the neglect of any potential metastatic
      mesorectal lymph nodes. This article presents the combined experience of several
      trials and indicates that neoadjuvant preoperative or adjuvant postoperative
      treatment may reduce the risk of local recurrence in a selected group of
      patients, and local excision results in overall survival comparable to the most
      aggressive treatment. Although the hypothetical improvement in morbidity and
      quality of life with local excision has not been demonstrated, the advantages of
      the local excision vs. radical surgery in the oncologic results seem obvious and
      require prospective randomized studies comparing both types of treatment.

PMID- 17436398
TI  - Systemic treatment of melanoma: quo vadis oncologist?

PMID- 17436399
TI  - Concurrent chemoradiotherapy with vinorelbine and a platinum compound followed by
      consolidation chemotherapy for unresectable stage III non-small cell lung cancer:
      preliminary results of a phase II study.
AB  - PURPOSE: To determine the efficacy, toxicity and survival of concurrent therapy
      with vinorelbine and a platinum compound with radiotherapy (RT), followed by
      consolidation chemotherapy with the same drugs, for locally advanced non small
      cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-seven patients with stage
      III NSCLC were included in this phase II study: median age 56 years (range 44
      71), males / females 49/8, ECOG performance status (PS) 1/2=27/30, stage IIIA/
      IIIB 11/46, squamous cell carcinoma 44, adenocarcinoma 7, adenoid cystic
      carcinoma 1 and large cell carcinoma 5. Treatment consisted of 2 cycles of
      chemotherapy with vinorelbine and cisplatin or carboplatin, given concurrently
      with RT, followed by 2-4 more cycles of consolidation chemotherapy with the same
      drugs. Twenty-two patients received amifostine for radio- and chemoprotection.
      RESULTS: Grade 3 or 4 toxicities were neutropenia and esophagitis in 19% of the
      patients each, and gastrointestinal toxicity in 17% of the patients. Of the 55
      patients evaluable for response, 23.64% achieved complete response (CR) and 40%
      partial response (PR) (overall response rate 63.64%). Progression-free survival
      curves showed 1- and 2-year values of 42% and 21%, respectively, and median time
      to progression 10.5 months. The 1- and 2- year disease-specific survival was 58%
      and 29%, and the median overall survival 15 months. CONCLUSION: Preliminary
      analysis indicates that concurrent vinorelbine and a platinum compound with RT
      followed by consolidation chemotherapy with the same drugs for advanced stage III
      NSCLC is well tolerated, has considerable activity and positive impact on
      survival.

PMID- 17436400
TI  - Dexamethasone, cyclophosphamide, etoposide and cisplatin (DCEP) for relapsed or
      refractory multiple myeloma patients.
AB  - PURPOSE: The purpose of this study was to assess the efficacy and toxicity of
      DCEP (dexamethasone, cyclophosphamide, etoposide, cisplatin), as third-line
      regimen in relapsed or refractory multiple myeloma (MM) patients. PATIENTS AND
      METHODS: Twelve patients (11 men, 1 woman, aged 38-73 years, median 58) with
      relapsed or refractory MM received 28 cycles of DCEP. Eleven out of 12 patients
      had already failed 4-6 cycles of VAD (vincristine, doxorubicin, dexamethasone),
      7/12 had received 2 or more lines of prior therapy and one of them had high-dose
      therapy with stem cell support. Seven out of 12 patients were candidates for
      megatherapy with autologous peripheral blood stem cells transplantation (ASCT)
      either as consolidation or as salvage treatment. Each cycle of DCEP consisted of
      cyclophosphamide 400 mg/m(2)/daily, cisplatin 15 mg/m(2)/daily and etoposide 40
      mg/m(2)/daily as a 24h infusion, all three drugs administered on days 1-4; plus
      dexamethasone i.v. bolus 40 mg daily, days 1-4. The dose of cisplatin was
      adjusted in case of renal impairment. G-CSF was administered daily from day +5 to
      recovery. The course was repeated every 28 days or was delayed 5-10 days
      according to the patient's clinical condition. RESULTS: The regimen was well
      tolerated with no major adverse reactions, except for grade 3 or 4 myelotoxicity
      of short duration. Responses were assessed using the EBMT criteria after the
      second cycle. Two out of 12 patients achieved complete remission (CR) and 5/12
      partial remission (PR), while 5/12 had no response (NR). The overall response
      (OR) was 58.3% with a median response duration 9 months (range 4-36). Four
      patients proceeded to successful peripheral blood stem cell mobilization and
      transplantation. CONCLUSIONS: DCEP is an effective and safe salvage treatment for
      relapsed or refractory MM patients which also offers the possibility for a
      successful peripheral blood stem cells collection in patients eligible for high
      dose therapy and ASCT.

PMID- 17436401
TI  - Large bowel endoscopy and management of colorectal cancer and its premalignant
      forms--endoscopy survey.
AB  - PURPOSE: To estimate the relationships between patients' clinical variables like
      age and sex with the endoscopical and histological findings of colorectal lesions
      and to assess the efficacy of endoscopy in diagnosing and treating polyps and
      early forms of colorectal cancer (CRC). PATIENTS AND METHODS: Analyzed were
      patients included in our database who were subjected to lower gastrointestinal
      tract endoscopy at our department for the last 15 years. RESULTS: 5107 patients
      were examined. In almost 1/5 (955) of them, the examination was for surveillance
      purposes. Women/men: 55%/45%. The number of patients with polyps was 1180. Polyps
      were diagnosed most frequently in patients aged 51-60 years and were located
      mostly in the sigmoid colon (43%). Patients with CRC were 613 and were diagnosed
      predominantly in the age group of 60-70 years (32%), most frequently in the
      rectum (38%), followed by the sigmoid colon (32%). 128 patients were diagnosed
      with early CRC. In 52 (40.62%) of them successful endoscopic therapy was carried
      out. No serious complications were observed except one case of late perforation
      after polypectomy, with a successful outcome. CONCLUSION: Lower gastrointestinal
      endoscopy is a highly efficient method for screening, diagnosis and therapy of
      colorectal polyps and early forms of CRC. It is still underused for screening
      purposes in patients after the age of 50 years.

PMID- 17436402
TI  - Flexible hysteroscopy in irregular uterine bleeding.
AB  - PURPOSE: The objective of our study was to analyze the possibilities of
      diagnostic flexible hysteroscopy in women with irregular uterine bleeding.
      PATIENTS AND METHODS: The study involved 661 women aged 26-72 years (mean 46.23)
      with mild to moderate irregular uterine bleeding who agreed to have invasive
      investigations. Diagnostic hysteroscopy by panoramic fibrohysteroscope Pentax LH
      150 II (5 mm in diameter) was performed initially to all patients, followed by
      classical dilatation and curettage (D & C). RESULTS: Different types of normal
      endometrium were found in 248 (37.52%) women, hyperplasia and polyposis in 300
      (45.39%), suspected changes for atypia and neoplasia in 82 (12.40%) and other
      different findings in 31 (4.69%). Subsequent D & C showed lack of adequate
      material from the uterine cavity in 26 (3.93%) women, in 538 (81.39%) the
      morphological findings were due to hormonal and dyshormonal reasons, 66 (9.98%)
      were with different precancer and cancer lesions and in 31 (4.69%) cases,
      clinically and morphologically, bleeding was due to the presence of submucosal
      myomas, intrauterine devices, residua and pathology of the chorion. CONCLUSION:
      The comparison of the hysteroscopy results with clinical and histological
      findings from D & C showed good diagnostic possibilities of the flexible
      hysteroscopy for evaluation of women with irregular bleeding (sensitivity 74.07%
      and specificity 90.61%). This examination is relatively simple, safe and requires
      simultaneous performance of a direct biopsy, in order to improve the accuracy of
      the results.

PMID- 17436403
TI  - Histopathological findings in postoperative specimens in cervical cancer patients
      with stages IB2-IVA after neoadjuvant chemotherapy and preoperative plus
      postoperative radiotherapy.
AB  - PURPOSE: To determine the incidence of the histopathological findings indicative
      for risk of recurrence in patients with locally advanced cervical cancer (LACC)
      who were treated with neoadjuvant chemotherapy (NCT) and radiation therapy (RT)
      before operation. PATIENTS AND METHODS: Sixty-three patients were included: 45
      patients (group 1) underwent external beam RT and then surgical treatment
      followed by postoperative RT, and 18 (group 2) patients were treated with NCT and
      surgery followed by postoperative RT. Surgery was class III-V radical
      hysterectomy with pelvic lymph node dissection (LND), and paraaortic LND at
      indication. NCT included 2-3 courses of cisplatin, ifosfamide and bleomycin
      administered at 3-week intervals. In group 1 FIGO stage IIB prevailed (n=29,
      64.4%). Forty-four (97.8%) patients had squamous cell carcinoma and 1 (5.6%)
      adenosquamous carcinoma. In group 2 stage IIB also prevailed (n=13, 72.2%),
      whereas all 18 (100%) patients had squamous cell carcinoma. The average age in
      group 1 and 2 was 48.8 years (range 31-69) and 46.3 years (range 32-64),
      respectively. RESULTS: In group 1 lymph node metastases (LNM) were found in
      35.56% of the cases, macroscopically detectable LNM in 15.6%, LNM above the
      common iliac artery level in 11.1%, multiple LNM (>3 LNM) in 17.8%, parametrial
      invasion in 4.4%, deep stromal invasion in 31.1%, lymphovascular space invasion
      (LVSI) in 13.3%, infiltration of canalis cervicalis in 15.6%, infiltration of
      isthmus uteri in 8.9% and ovarian metastases in 4.4%. In group 2 LNM were found
      in 38.89% of the patients, macroscopically detectable metastases in 22%, multiple
      (>3 LNM) LNM in 17%, LNM above the common iliac artery level in 22%, deep stromal
      invasion in 47%, parametrial infiltration in 24%, LVSI in 12%, tumor infiltration
      in canalis cervicalis in 12%, and ovarian metastases in 6%. CONCLUSION: NCT
      followed by surgical treatment and RT leads to postoperative histological results
      that are not worse than the standard preoperative RT approach.

PMID- 17436404
TI  - Cancer incidence among Bulgarian medical radiation workers: epidemiological
      study.
AB  - PURPOSE: To look for the cancer incidence in a cohort of medical radiation
      workers in relation to work history (year of first employment, duration of
      occupational exposure, and radiation doses received for the whole period).
      MATERIALS AND METHODS: In this retrospective study the cancer incidence among 315
      medical workers (radiotherapists, diagnostic radiologists and technical
      personnel) was compared with that of 320 other medical specialists not having
      occupational contacts with radiation sources, who worked in hospitals in the
      territory in Sofia for the period 1960-2000. Data concerning incident cancer
      occurrence were obtained via a questionnaire. Data for individual doses were
      extracted from the National System of Individual Dosimetric Control. Descriptive
      statistics, x(2) test, Fisher's exact test and ANOVA analysis were used. RESULTS:
      Cancer was more frequently diagnosed among radiation workers compared to other
      medical specialists (p=0.018). When analyzing by cancer type breast cancer was
      more frequently diagnosed in radiation workers (p=0.037). No significant relation
      was observed between cumulative radiation dose and cancer incidence (p=0.12), or
      cancer incidence by different cancer localizations (p=0.13). Similarly, no
      difference was found between year of first employment and cancer development in
      cases and controls (p=0.854 and p=0.178, respectively). Longer whole working
      period was significantly connected with lower cancer incidence in cases (p=0.015
      and p=0.062 for cases and controls, respectively). CONCLUSION: The present study
      shows that cumulative dose and the duration of work in an ionizing radiation
      environment does not substantially influence cancer development. Although we
      found higher cancer occurrence among cases compared to controls, those two
      factors do not give us ground to confirm that working in an ionizing radiation
      environment increases cancer incidence. It is important to continue the
      monitoring of the health status of medical radiation workers.

PMID- 17436405
TI  - Comparison between CoFactor and Leucovorin activity applied in combination with 5
      fluorouracil against two human colon cancer cell lines.
AB  - PURPOSE: The reduced folate leucovorin (LV) has been used for over 30 years as an
      enhancer of 5-fluorouracil (5-FU) antitumor activity. CoFactor (CoF) is a calcium
      salt of LV's active metabolite. Thus, administration of CoF can prevent decrease
      of intratumoral folate, which was recognized as the main reason for resistance of
      tumors to 5-FU treatment. The aim of this study was to investigate the cytotoxic
      activity and type of interactions for 5-FU and CoF applied in combination, in
      comparison to combination of 5-FU and LV, against human colon cancer cell lines
      LS- 174 and HT-29. METHODS: The single agent activity was estimated in
      concentration range from 0.1 to 300 microM for 5-FU, CoF, and LV. In combined
      treatment each concentration of 5-FU (0.1, 1 and 10 microM) was matched with each
      concentration of CoF or LV (1, 10 and 100 microM). In both experiments the
      sulforodamine B cytotoxic test was used to assess drugs' activity after 72 h of
      incubation with cells. The type of interactions in combinations was calculated
      with the isobole method. RESULTS: 5-FU showed similar activity against LS-174 and
      HT-29 cell lines (IC50=30.8 and 21.6 microM, respectively). While LV affected
      both cell lines in a slightly proliferative manner, CoF showed cytotoxic effect
      on both cell lines, being more active against HT-29 cell (IC50=25.7 microM) and
      less active on LS-174 cells (IC50=72.6 microM). Addition of LV did not change the
      cytotoxicity of 5-FU, especially against LS-174 cells, and synergism was found
      only in HT-29 cells when LV was applied in high concentrations (10 and 100
      microM). However, the combination of 5-FU with CoF revealed synergistic and
      additive interactions in LS-174 and HT-29 cells, respectively. CONCLUSION: These
      results should be taken into consideration when planning or analyzing the results
      of clinical trials using combination of CoF and 5-FU.

PMID- 17436406
TI  - Deregulated sequential motion of centromeres induced by antitumor agents may lead
      to genome instability in human peripheral blood lymphocytes.
AB  - PURPOSE: Segregation of chromosomes in anaphase is preceded by a sequential order
      of centromere separation. Alteration of the sequence of centromere separation or
      premature centromere division (PCD) has been found to be significantly higher in
      populations exposed to various xenobiotics. The purpose of this study was to
      investigate if PCD induced by various cytostatics can alter the stability of
      chromosomes and lead to aneuploidy. MATERIALS AND METHODS: Peripheral blood
      lymphocytes of 10 healthy, non smoking subjects were exposed to 8-Cl-cAMP at a
      dose of 1, 5 and 15 microM, paclitaxel at a dose of 0.01, 0.05 and 0.2 microM,
      and cycloheximide (CX) at a dose of 5, 10 and 25 microg/ml. By using the
      cytohalasin B (CB)-micronucleus (MN) test in vitro, in combination with
      fluorescent in situ hybridization (FISH), the presence of MN was analyzed in 1000
      binuclear cells for each experimental and negative control group. For analysis of
      MN content we used the alpha-centromeric probe for chromosome 18. RESULTS: 8-Cl
      cAMP and paclitaxel induced an increase in the frequency of MN in peripheral
      blood lymphocytes. 8-Cl-cAMP and paclitaxel proved clastogenic, i.e. they
      increased the frequency of MN and induced PCD in all respective doses. CX proved
      not clastogenic in the respected doses when using the CB-MN test in vitro,
      although CX is a specific PCD inducer. No correlation of PCD and aneuploidy of
      chromosome 18 was found in cells exposed to 8-Cl-cAMP and paclitaxel by using
      FISH. In cells exposed to CX we found PCD of chromosome 18 in binuclear cells and
      single signals in scarce MN. These findings were not statistically significant
      compared to the negative control group. CONCLUSION: Our results show that the
      properties of the investigated antitumor agents to induce PCD in peripheral blood
      lymphocytes and, therefore, aneuploidy and genome instability, is highly based on
      the nature of the alteration of centromere function, i.e. the temporal order of
      centromere kinetics are more regulated through the sequence of centromere
      separation than by the segregation processes. We suggest that PCD induced by
      novel antitumor agents could be included in preclinical and clinical genetic risk
      assessment analysis.

PMID- 17436407
TI  - Microsatellite instability in Bulgarian patients with endometrial cancer.
AB  - PURPOSE: Microsatellite instability (MSI) is a frequent event in different types
      of cancer. In several studies MSI was shown to have both clinical and prognostic
      value. The aim of our study was to determine the frequency of MSI in Bulgarian
      patients with endometrial cancer (EC) and the possible relation of this
      phenomenon to their clinicopathological characteristics. PATIENTS AND METHODS: A
      total of 33 histologically confirmed EC patients were analyzed for tumor MSI
      using a panel of 6 microsatellite markers. RESULTS: We identified MSI in 30% of
      endometrial cancer cases. Six of them had high degree of MSI (MSI-H), and 4
      displayed low degree of MSI (MSI-L). CONCLUSION: The frequency of MSI in
      Bulgarian EC patients does not differ significantly from that reported in other
      European studies.

PMID- 17436409
TI  - Relationship of serum levels of tumor markers with tissue expression of gene
      products in ovarian carcinoma.
AB  - PURPOSE: The aim of this prospective study was to determine serum levels and
      tissue expression of CA125, CA 15-3, p53, HER-2 and nm23 tumor markers, which are
      used in the detection and follow up of patients with ovarian carcinoma. PATIENTS
      AND METHODS: 19 patients with malignant and benign ovarian tumors were included
      in this study. Serum levels of CA125, CA 15-3 and p53 tumor markers were detected
      in preoperative and postoperative blood samples using ELISA technique. Tissue
      expression of p53, HER-2 and nm23 were examined using immunohistochemistry.
      RESULTS: All serum tumor markers were elevated in patients with ovarian
      carcinoma. Serum level of CA 15-3 was increased in patients with ovarian
      carcinoma (median 48.33 U/ml, normal range 0-36), while it was normal in patients
      with benign ovarian tumors (median 20.67 U/ml; p >0.05). CA125 serum values were
      strikingly increased in ovarian carcinoma (median 264.16 IU/ml, normal range 0
      35) and benign ovarian tumors (median 119.59 IU/ml; p <0.05). Serum levels of p53
      in patients with ovarian carcinoma were increased (median 0.69 U/ml, normal range
      0-0.50) compared to patients with benign tumors (0.32 U/ml; p <0.05).
      Histological HER-2 overexpression was detected in 7 cases, including 4 with
      strong (score 3+ and 2+) and 3 with weak or no HER-2 expression (score 1+ and 0)
      in ovarian carcinoma tissue; in benign tumors HER-2 overexpression was detected
      in 1 case (p >0.05). Strong overexpression of p53 was detected in 3 cases with
      malignant and none with benign tumors (p >0.05); and strong overexpression of
      nm23 was detected in 5 cases with malignant and 2 with benign tumors (p >0.05).
      CONCLUSION: Serum levels of CA125, CA 15-3 and p53 are strikingly increased, as
      well as the expression of HER-2 and p53 in carcinomatous tissue. Detection and
      analysis of multiple tumor-specific markers in serum and tissue can give useful
      clinical information for the management of ovarian carcinoma and can also improve
      the sensitivity and specificity of these markers.

PMID- 17436408
TI  - HER-2 expression in uterine cervix carcinogenesis.
AB  - PURPOSE: To assess the expression and clinical significance of HER-2
      protooncogene in the uterine cervix carcinogenesis. PATIENTS AND METHODS: We
      examined 69 tissue samples of low grade cervical squamous intraepithelial lesions
      (SIL) (n=16), high grade SIL (n=11) portio vaginalis uteri (PVU) carcinoma in
      situ (n=11) and PVU invasive carcinoma, stage IA-IIA (n=13; study group) and 18
      samples without SIL or malignancy (control group). The expression of HER-2 was
      detected immunohistochemically using a monoclonal antibody. Fisher's exact test
      was used to assess statistical significance. By establishing sensitivity and
      specificity of the test, the level of reliability of these analyses was
      determined as a possible screening method for early detection of changes in the
      uterine cervix. RESULTS: Overexpression of HER-2 was found to increase in direct
      relation to the grade of the cervical lesions. Statistically significant
      difference was found in the frequency of overexpression in patients with high
      grade SIL, PVU carcinoma in situ and PVU invasive carcinoma compared with the
      control group. High sensitivity was of great diagnostic significance for the
      detection of these types of changes in the uterine cervix. On the basis of high
      predictive values it can be concluded that in patients with HER-2 overexpression
      there is a great possibility that they have premalignant or malignant changes in
      the uterine cervix. CONCLUSION: Our results indicate that overexpression of HER-2
      oncogene may play an important role in cervical carcinogenesis. However, more
      extensive series of samples is required to establish the prognostic significance
      of HER- 2 in cervical carcinogenesis.

PMID- 17436410
TI  - Serum level changes of matrix metalloproteinases 2 and 9, vascular endothelial
      growth factor and epidermal growth factor receptor during platinum-based
      chemotherapy in advanced non-small cell lung cancer patients.
AB  - PURPOSE: To evaluate serum changes of matrix metalloproteinases (MMPs) 2 and 9,
      vascular endothelial growth factor (VEGF) and epidermal growth factor receptor
      (EGFR) levels in patients with advanced non-small cell lung cancer (NSCLC) and
      their association with main clinicopathological parameters during chemotherapy
      with cisplatin and gemcitabine. PATIENTS AND METHODS: In this prospective study,
      consecutive patients with stage III and IV NSCLC were enrolled. Serum MMP2 and 9,
      VEGF and EGFR levels were monitored in blood samples taken on day 1 of starting
      chemotherapy (baseline 1st), and after 3 cycles of chemotherapy (2nd) using
      commercial sandwich ELISA method. RESULTS: 116 patients were evaluated. Males /
      females 100 / 6, ECOG performance status (PS) 0/1/2: 47/65/4, stage III / IV:
      49/67, squamous /adeno/large cell carcinoma 41/31/19. Forty-two (36%) patients
      achieved partial response (PR), 32 (28%) stable disease (SD) and 42 (36%) showed
      progressive disease (PD). Mean serum values -/+ standard deviation (SD) of the
      analyzed markers at baseline/at response evaluation were: EGFR 86 -/+ 87/96 -/+
      47 fmol/ml; MMP9 236 -/+ 156/162 -/+ 133 ng/ml ; MMP2 525 -/+ 189/569 -/+ 201
      ng/ml; VEGF 555 -/+ 476/599 -/+ 611 pg/ml; VEGF adjusted for platelets (PLT) 1.9 
      /+ 1.45/2.4 -/+ 2.78 pg/10(6). In logistic regression model for response rate
      adjusted for stage, the increase in MMP9 levels during chemotherapy (mean = 74
      ng/ml -/+ SD 140) was predictive for progression (p=0.041) with 5% increase in
      the odds of progression for an increase of 10 ng. CONCLUSION: MMP9 level increase
      was found to be predictive of disease progression. EGFR levels could refl ect
      extracellular domain (ECD) loss from resistant cells and its shedding into the
      circulation.

PMID- 17436412
TI  - Primary classic penile Kaposi's sarcoma in an elderly HIV-negative patient:
      report of a case and review of the literature.
AB  - Kaposi's sarcoma (KS) is a neoplastic vascular tumor. The case of a 91-year-old
      HIV-negative and HHV-8-positive with two reddish-purple lesions (one
      pedunculated) on the inner layer of the prepuce is described. Although primary
      penile KS is a relatively uncommon lesion in HIV-negative men, dermatologists and
      urologists should consider this possibility when treating non-specific penile
      lesions.

PMID- 17436411
TI  - Acute heart failure after treatment with 5-fluorouracil.
AB  - Anthracycline cardiotoxicity is cumulative and can cause congestive heart
      failure. The cardiotoxicity caused by 5-fluorouracil (5-FU) is acute and is
      usually observed during the first cycle of chemotherapy. We present the case of a
      female patient operated on for colorectal cancer and receiving her first
      postoperative chemotherapy cycle. Three hours after the initiation of continuous
      5-FU infusion she developed signs of acute heart failure (AHF) and pulmonary
      edema. The patient did not have any previous history of heart disease. Symptoms
      resolved 24 hours from the onset of the episode after the initiation of the
      relevant emergency therapy. One of the most common symptoms related to 5-FU
      cardiotoxicity is chest pain. In case of such a toxicity treatment should be
      switched to another antineoplastic agent.

PMID- 17436413
TI  - Minimal invasive treatment of cervical rhabdomyosarcoma in an adolescent girl.
AB  - Rhabdomyosarcomas are the most common soft tissue sarcomas in childhood and
      adolescence. In cases of minimal cervical invasion, less invasive local excision
      in combination with adjuvant chemotherapy has resulted in excellent survival
      rates with complete preservation of the bladder, rectum, uterus and vagina.
      Herein we present the case of an adolescent girl with a large rhabdomyosarcoma of
      the uterine cervix treated with minimal invasive therapy.

PMID- 17436414
TI  - Primary solitary eosinophilic granuloma of the brain and postoperative
      radiotherapy: a clinical case.
AB  - A case of solitary eosinophilic granuloma (EG) of the brain in a 53-year-old
      woman is presented. The tumor developed in the anterior cranial fossa causing
      destruction of the skull basis and the retrobulbar space, accompanied by vision
      impairment. The tumor was partially excised and the patient was irradiated
      postoperatively with 40 Gy 6 MV x-rays, followed by 10 cycles of chemotherapy.
      Follow-up computed tomography (CT) showed no response at 30 Gy and no progression
      during chemotherapy. Attention is drawn to cases of EG indolent in growth but
      resistant to radiation and chemotherapy.

PMID- 17436415
TI  - Therapy-related acute promyelocytic leukemia after treatment with radioiodine for
      thyroid cancer: case report with literature review.
AB  - Therapy-related acute promyelocytic leukemia (t-APL) is a rare but known
      complication of chemotherapy and/or radiation therapy. Approximately 200 cases of
      t-APL have been reported in the literature up until now. The development of t-APL
      after radioiodine therapy is very rare, keeping in mind the very low doses of
      radiation exposure of the patient. We present a case of a 47-year-old woman with
      t-APL t15;17(q22;q21) developed after radioiodine treatment for thyroid
      carcinoma. The patient was treated with chemotherapy and achieved complete
      response lasting for 3(+) years. The patient's excellent response to treatment
      supports the data of the relevant literature that t-APL is associated with a
      better therapeutic result than the other subtypes of secondary acute myeloid
      leukemia (AML).

PMID- 17436416
TI  - J BUON and important biomedical databases.

PMID- 17436417
TI  - Plasminogen activator inhibitor-1 gene 4G/5G polymorphism in cancer patients.

PMID- 17436418
TI  - If Jules Verne had a stage IV lung cancer; a science fiction solution of cancer.

PMID- 17436419
TI  - Professor Miltiades Papamiltiades (1907-1987): 20 years since the death of an
      eminent Greek anatomopathologist and cytologist.
AB  - Professor Miltiades Papamiltiades was an outstanding Greek anatomopathologist and
      cytologist. By his researches on lymphatic vessels and the invention of new
      staining techniques in exfoliative cytology, continued the work of his
      predecessor George Papanicolaou against the cancer.

PMID- 17436420
TI  - A world less silent: celebrating Jay Katz's contributions to law, medicine, and
      ethics. Proceedings of a meeting to honor Jay Katz. October 15, 2004. New Haven,
      Connecticut, USA.

PMID- 17436421
TI  - EBRT less effective for early-stage prostate cancer.

PMID- 17436422
TI  - Toremifene might improve side effects of ADT.

PMID- 17436423
TI  - Benefits of tamoxifen persist long after treatment ends.

PMID- 17436424
TI  - Copper moves across membranes during angiogenesis.

PMID- 17436425
TI  - Inflammatory polyarthritis increases death risk.

PMID- 17436426
TI  - Otosclerosis and stapes surgery. Proceedings of an international symposium. April
      2004. Saas Fee, Switzerland.

PMID- 17436427
TI  - PSA: past, present and future. Should we find prostate cancer or should we look
      for it? Proceedings of an international meeting. September 15-17, 2005. Milan,
      Italy.

PMID- 17436428
TI  - Abstracts from the 15th Conference on Hemoglobin Switching. September 14-18,
      2006. Oxford, United Kingdom.

PMID- 17436429
TI  - Five-gene signature in non-small-cell lung cancer.

PMID- 17436430
TI  - Five-gene signature in non-small-cell lung cancer.

PMID- 17436431
TI  - Five-gene signature in non-small-cell lung cancer.

PMID- 17436432
TI  - Five-gene signature in non-small-cell lung cancer.

PMID- 17436433
TI  - Autoimmune pancreatitis.

PMID- 17436434
TI  - Autoimmune pancreatitis.

PMID- 17436435
TI  - Modeling forest production: scientific tools, data needs and sources, validation
      and application. Proceedings of an international conference. April 19-21, 2004.
      Vienna, Austria.

PMID- 17436436
TI  - Primary percutaneous coronary intervention.

PMID- 17436437
TI  - Primary percutaneous coronary intervention.

PMID- 17436438
TI  - Diet and exercise to ameliorate frailty in obese older adults.

PMID- 17436439
TI  - Retraction notice to "High-level expression and purification of recombinant huGM
      CSF(9-127)/IL-6(29-184) fusion protein in Escherichia coli" [Protein Express.
      Purif. 42 (2005) 278-285].

PMID- 17436440
TI  - Pathologic quiz case 2. Chondroma of the larynx.

PMID- 17436441
TI  - Kyoshiro Yamakawa, MD, and temporal bone histopathology of Meniere's patient
      reported in 1938.

PMID- 17436442
TI  - Laryngeal liposarcoma.

PMID- 17436443
TI  - DeParle's double play. Triad board member also works for CCMP.

PMID- 17436444
TI  - Flu game plan. Providers welcome CDC pandemic recommendations.

PMID- 17436445
TI  - Trustees of the Year 2007. Behavior modification. Ochs revamps board bylaws in
      wake of power struggle.

PMID- 17436446
TI  - Gastrointestinal endoscopy in pregnant and lactating women: emerging standard of
      care to guide decision-making.

PMID- 17436447
TI  - NIH funding: what does the future look like?

PMID- 17436448
TI  - NIH funding: what does the future look like?

PMID- 17436449
TI  - [Questions and answers about bisphosphonates].

PMID- 17436450
TI  - [What's new in lung cancer].

PMID- 17436453
TI  - Current awareness in prenatal diagnosis.

PMID- 17436451
TI  - Prevalence of H. pylori infection in renal transplant recipients.

PMID- 17436454
TI  - Perinatal death in twins. Author's reply on absolute risk.

PMID- 17436455
TI  - Advances in cardiac MRI: The Dallas Heart Study.

PMID- 17436456
TI  - Advances in cardiac MRI: The multi-ethnic study of atherosclerosis.

PMID- 17436458
TI  - [Blood pressure room--a room under pressure?].

PMID- 17436457
TI  - [Exaggerated advice on balanitis in a standard book--information center a
      resource].

PMID- 17436459
TI  - Penrose's Law in Ireland: an ecological analysis of psychiatric inpatients and
      prisoners.
AB  - Penrose's Law states that as the number of psychiatric inpatients declines, the
      number of prisoners increases. We studied data from the annual census of
      psychiatric inpatients and prison statistics in Ireland. Between 1963 and 2003,
      the number of psychiatric inpatients decreased by 81.5% (a five-fold decrease)
      and the average number of prisoners increased by 494.8% (a five-fold increase)
      (Spearman's rho=-0.992, P<0.001). The absolute decline in psychiatric inpatients
      greatly exceeded the increase in prisoners. This net de-institutionalisation
      appears particularly marked in Ireland compared to England; this may relate to
      ecological study designs or differences in prison, health or re
      institutionalisation practices.

PMID- 17436460
TI  - Dissatisfaction with "do not attaempt resuscitation" orders, a nationwide study
      of Irish consultant physician practices.

PMID- 17436461
TI  - Legibility of doctors' signatures.

PMID- 17436462
TI  - In response to article on CODEIRE study.

PMID- 17436463
TI  - [First in man registry with a bioabsorbable polymer based sirolimus-eluting
      stent: six month angiographic and 12 month clinical results (MedistreExcel Drug
      eluting STent TRiAL)].

PMID- 17436468
TI  - Distribution of soluble guanylyl cyclase in rat retina.
AB  - The nitric oxide (NO)-cGMP pathway is implicated in modulation of visual
      information processing in the retina. Despite numerous functional studies of this
      pathway, information about the retinal distribution of the major downstream
      effector of NO, soluble guanylyl cyclase (sGC), is very limited. In the present
      work, we have used immunohistochemistry and multiple labeling to determine the
      distribution of sGC in rat retina. sGC was present at high levels in inner retina
      but barely detectable in outer retina. Photoreceptors and horizontal cells, as
      well as Muller cells, were immunonegative, whereas retinal ganglion cells
      exhibited moderate staining for sGC. Strong immunostaining was found in
      subpopulations of bipolar and amacrine cells, but staining was weak in rod
      bipolar cells, and AII amacrine cells were immunonegative. Double labeling of sGC
      with neuronal nitric oxide synthase showed that the two proteins are generally
      located in adjacent puncta in inner plexiform layer, implying paracrine
      interactions. Our results suggest that the NO-cGMP pathway modulates the neural
      circuitry in inner retina, preferentially within the cone pathway.

PMID- 17436469
TI  - Emergency embolectomy for treatment of acute middle cerebral artery occlusion.

PMID- 17436470
TI  - Clinical paradigms revisited.

PMID- 17436471
TI  - The absence of many voices in protest.

PMID- 17436472
TI  - Specialist fungi, versatile genomes.

PMID- 17436473
TI  - HIV: breast still best.

PMID- 17436474
TI  - [An invitation].

PMID- 17436475
TI  - Current models of the ocular motor system.
AB  - This chapter gives a brief overview of current models of the ocular motor system.
      Beginning with models of the final ocular pathway consisting of eye plant and the
      neural velocity-to-position integrator for gaze holding, models of the motor part
      of the saccadic system, models of the vestibulo-ocular reflexes (VORs), and of
      the smooth pursuit system are reviewed. As an example, a simple model of the 3-D
      VOR is developed which shows why the eyes rotate around head-fixed axes during
      rapid VOR responses such as head impulses, but follow a compromise between head
      fixed axes and Listing's law for slow VOR responses.

PMID- 17436476
TI  - Anti-Cr(a): pregnancy and transfusion support.

PMID- 17436478
TI  - Dialogues on depression management: the primary care and specialist perspectives.
AB  - Depression is a major public health problem in the United States and is
      responsible for an enormous economic burden and loss of productivity and quality
      of life. In many cases, PCPs are well situated to identify and treat unrecognized
      depression, but an optimal treatment program often comprises both medical and
      psychotherapeutic interventions. Many collaborative models that integrate the
      efforts of PCPs, psychiatrists, behavioral health organizations, and workplace
      assistance programs are being tested and may prove to be the best direction for
      improving care for patients with depression. Looking ahead, improvement in
      treatment of depression will depend on numerous factors, including educating
      health care practitioners to recognize silent depression, expanding current
      collaborative models to cover more of the population, involving MCOs and payers
      in the development of effective treatment systems, and improving workplace
      support programs to encourage more patients to seek appropriate care.

PMID- 17436477
TI  - A reminder that ZZAP reagent removes complement in addition to IgG from coated
      RBCs.

PMID- 17436479
TI  - Depression management: applying skills in the clinical setting.
AB  - Primary care and specialist providers face different challenges - and often make
      different choices when treating a severely depressed patient. To help attendees
      learn from the experiences of primary care physicians and mental health
      professionals, and to demonstrate how to incorporate the skills of each, Collins
      (the internist) and Escobar (the psychiatrist) reviewed two actual cases [the
      names of the patients have been changed] at the MOOD symposium in Philadelphia.
      They then advised on their chosen approaches to managing them. Questions from
      symposium attendees are referred to as audience.

PMID- 17436480
TI  - Organized care and employee assistance programs.

PMID- 17436481
TI  - Lack of access in rural regions.

PMID- 17436482
TI  - Unions and collective bargaining.

PMID- 17436483
TI  - Cultural diversity and special populations.

PMID- 17436484
TI  - Provider perspective: and given the opportunity, you have done what?

PMID- 17436485
TI  - Obesity epidemic: what treatments work and whom do you treat?

PMID- 17436486
TI  - The future of the health care marketplace: the quest for value.

PMID- 17436487
TI  - [Ultrasonic studies of the human embryo sac].
AB  - The growth of the embryo sac and of the uterus was determined between the 5th and
      12th weeks of amenorrhoea in 91 normal pregnancies. 24 measurements of the
      ovaries and the uterus were made for each case by means of two-dimensional
      echograms. The averages, the standard deviations, the deviations of the mean, the
      correlation coefficients and the regression polynomials are reported for each of
      the dimensions measured. The results are compared with those obtained by other
      authors. The dimensions that gave the best indication of the evolution of
      gestation were the area and perimeter of the ultrasonic scans of the embryo sac
      and of the uterus as well as the cephalo-caudal diameter of the embryo sac.

PMID- 17436488
TI  - [The value of estimating fetal age by means of ultrasound].
AB  - The authors estimated in 1,000 women the length of gestation using two criteria:
      the date of the last menstruation and the results of ultrasonic examination
      (ovarian sac and biparietal diameters). The women were allocated to one of four
      groups according to the details of their menstrual history: (1) last periods
      specified precisely, 28 +/- 5 days ; (2) last periods specified precisely, with
      longer or shorter cycles; (3) last periods doubtful, or (4) last periods unknown.
      An additional subdivision was made according to the foetal age at the time of the
      estimation. Statistical analysis showed that the average length of pregnancy
      measured by ultrasound was similar in all groups and series; only the standard
      deviation increased slightly towards the end of pregnancy. The results were
      similar to those obtained by estimating the length of gestation from the date of
      ovulation.

PMID- 17436489
TI  - [Fetal cephalometry and thoracometry during pathological pregnancies].
AB  - Cephalometry and thoracometry by means of ultrasound represent two useful methods
      of foetal biometry. Cephalometry, the technique of which is simple and well
      documented, is irreplaceable as a method of monitoring high risk pregnancies and
      as a means of detecting anomalies of foetal growth. However, when there is
      evidence of chronic foetal distress, thoracometry can compensate for the
      diagnostic shortcomings of cephalometry. In cases of diabetic pregnancy only
      thoracometry is able to detect foetal oedema. Combination of the two parameters
      makes possible, when only one measurement is made, a good approximation of the
      weight of the foetus even in pathological pregnancies.

PMID- 17436490
TI  - [Echographic investigation of the placenta during normal and pathological
      pregnancies].
AB  - Echographic investigation of the placenta has proved to be very valuable in
      monitoring pathological pregnancies. Precise localization of the placental area
      has led to a considerable increase in the practice of amniocentesis;
      placentography has enabled the authors to carry out biopsies of the placenta
      successfully. Diagnosis of gravidic metrorrhagia is greatly facilitated by
      echotomography, as long as the examination is carried out under good conditions,
      after filling of the bladder. A negative result may avoid the need for prolonged
      hospitalization. Systematic measurement of placental thickness at about the 36th
      week of pregnancy can detect unsuspected placental oedema or placental hypotrophy
      responsible for reduced intrauterine growth.

PMID- 17436491
TI  - [Recent developments in laparoscopic ovarian biopsy].

PMID- 17436492
TI  - [Experimental treatment of menopausal disorders by an estrogen-progestogen
      combination with the estrogen dominant or mixed and then a weak estrogen
      progestogen combination].

PMID- 17436493
TI  - [Induction of labor with the help of the prostaglandins E1, E2, F1alpha, and
      F2alpha].
AB  - The authors report their experiences in inducing labour between the 34th and the
      43rd week of amenorrhea by the administration of prostaglandins. The detailed
      results of several series are compared: PGF2alpha by venous perfusion alone (100
      cases) or associated with buccal oxytocin (100 other cases), PGE1 by perfusion
      (25 cases), PGF2alpha and PGE2 by intra-amniotic injection in cases of fetal
      death (25 cases). After an extremely detailed discussion of the maternal and
      fetal results and of the secondary effects, the authors explain the indications,
      the means of introduction, and also the dosages. Finally they compare the effects
      of prostaglandins in full-term inductions and in so-called therapeutic abortions.

PMID- 17436494
TI  - [The present limits of fetal monitoring during labor: future prospects].
AB  - On the basis of cases in which both fetal cardiac rhythm and pH in utero were
      monitored, the authors studied the prognostic value of anomalies in fetal cardiac
      rate. There was a good correlation between the absence of anomalies in monitoring
      and fetal wellbeing. In cases with an anomaly in the rhythm, the monitoring
      represented only a warning signal in the diagnosis of fetal distress, the only
      certain indicator being the pH measurement in utero. Nevertheless, the increasing
      use of fetal monitoring seems to have had a marked effect on perinatal mortality
      in Professor Magnin's obstetrics department.

PMID- 17436495
TI  - [The procedure to be adopted in cases of breech presentation: use of the vacuum
      extractor].
AB  - The authors review the advantages of a non-standard method of extraction in cases
      of breech presentation, the vacuum extractor. This method should not only replace
      total extraction in cases of frank breech, but should also find much wider
      applications. In fact the technique, which is easily applied and always
      effective, permits extraction in cases of frank breech by the vaccum cup at the
      stage of complete dilatation, preferably when the breech is well engaged, without
      serious complications. The authors then explain how they have used the vacuum
      extractor in their general practice in cases of breech presentation: in 100
      cases, the extractor was used 41 times, total extraction was used 19 times,
      caesarian section, 18 times, partial extraction 9 times, and there was no
      intervention in 9 cases some of which were terminated by the Mauriceau method.
      The corrected mortality was 1% and the corrected morbidity with an Apgar score of
      less than or equal to 6 et 1 minute, was 16.3 percent (excluding premature
      infants of less than 1,500 g and malformed infants). The use of the total
      extraction principle and particularly of the vacuum extractor avoids the
      occurrence of the unexpected and the necessity for the obstetrician to improvize
      a more difficult and perilous method of rescue.

PMID- 17436496
TI  - [A new conception of the physiology of amniotic circulation].
AB  - A histological study of the ovular membranes made by the authors showed that they
      represent an organ closely resembling the placenta and led them to believe that
      the metabolic processes that regulate the amniotic fluid occur in all the
      membranes and more especially in the region of the cytotrophoblast in the chorion
      that delimits the amniotic cavity. In the same way that the concept of a
      placental barrier has been abandoned in relation to the materno-fetal exchanges
      in the intervillous space, a concept that regarded the exchanges as simple
      diffusion across a theoretical membrane, the authors think that the concept of
      diffusion, simple transudation, across a little differentiated membrane such as
      the amnion must be abandoned in relation to the formation of the amniotic fluid.
      The placenta and the membranes form a whole in which the trophoblast plays a
      fundamental role in the feto-maternal exchanges in both the intervillous space
      and the amniotic cavity. This oneness makes possible an explanation of the
      physiopathology of both quantitive and qualitative regulatory disorders of the
      amniotic fluid.

PMID- 17436497
TI  - [A trial of the treatment of the premenstrual syndrome by acupuncture].
AB  - After a clinical and physiopathological review of the premenstrual syndrome, the
      author reports six cases of patients showing these symptoms who were treated
      exclusively by acupuncture. The clear improvement shown makes it worthwhile to
      continue the trial and to extend it to include other domains of functional
      gynaecology.

PMID- 17436498
TI  - [Cauterization of the uterine cervix: electrocauterization and cryotherapy].
AB  - The authors review the controversies that still continue concerning
      electrocauterization of the uterine cervix. They emphasize the value of
      colposcopy in the evaluation of the cervix. This examination is indispensable in
      selecting the cases for treatment: ectropion and benign malpighian dysplasias are
      clear indications for cauterization. Contraindications and technical problems are
      discussed. The indications are given for bipolar biactive, and bipolar monoactive
      electrocauterization, respectively, or for electroresection by means of a
      metallic loop. The different cicatrization times after electrocauterization are
      reviewed as well as the possibility of sequelae: in certain cases sequelae can be
      more or less avoided by previous therapeutic precautions and by careful attention
      to the duration of cauterization. Cauterization of the uterine cervix by
      cryotherapy seems to be worthy of particular consideration: the first results are
      reported. It seems to be simpler to use than diathermocauterization and in the
      great majority of cases the results seem to have been good.

PMID- 17436499
TI  - [A little known aspect of feto-maternal incompatibility: anti-HL-A immunization].

PMID- 17436500
TI  - [Hyperthyroidism associated with hydatid moles].
AB  - With reference to a 25-year-old patient who developed manifestations of clinical
      and paraclinical hyperthyroidism during the course of a molar pregnancy, the
      authors studied correlations between the two conditions. Hyperthyroidism is the
      result of hyperstimulation, of placental origin, and disappears when the
      hyperstimulation disappears. The placenta is capable of producing a TSH-like
      factor. HENNEN and HERSCHMAN established the existence of human chorionic
      thyrotropin which has hormonal and physicochemical properties similar to those of
      TSH, and which has just been isolated by Japanese workers. In fact during the
      development of a mole, it is molar HCT (or MHCT) that constitutes either a
      precursor or a subunit of HCT. However, hyperthyroidism remains rare during the
      course of molar pregnancies, a fact that has not yet been explained.

PMID- 17436501
TI  - [The obstetrical and fetal prognosis after metrorrhagia in the first trimester of
      pregnancy: with reference to 187 cases].
AB  - The authors followed 187 pregnancies in which metrorrhagia had occurred in the
      first trimester, but which had not resulted in abortion. In these patients, the
      authors studied particularly changes in hormone levels in the urine and the
      relation between these levels and fetal prognosis. If hormonal deficit is related
      to fetal prognosis, the relationship does not appear to be a direct one: estrogen
      deficiency is discovered more often than luteal deficiency; the more serious the
      estrogen deficiency the more often is it associated with severe progesterone
      deficiency; The number of fetal malformations did not seem to be any higher in
      patients who had presented metrorrhagia in first trimester than in patients whose
      pregnancy was normal. Any higher in patients who had presented metrorrhagia in
      the pregnancy on one hormone analysis, whether or not it is abnormal. The
      examinations should be repeated so that the evolution may be followed carefully.

PMID- 17436502
TI  - [Emergency haemostasis hysterectomy in obstetrics].
AB  - The study was based on 15 cases of haemostasis hysterectomy: 7 cases after
      caesarian section, 8 cases after normal delivery. The etiological circumstances
      varied, the haemorrhage being due to uterine rupture, to an accident during
      delivery related to uterine atony, to placenta accreta, or to a coagulation
      disorder. In these circumstances, the most satisfactory operation seems to be
      total hysterectomy with bilateral ovariectomy, conservation of the ovaries being
      justified in younger women. The authors describe the precautions that they feel
      are essential during labour or during a caesarian section to avoid such
      complications.

PMID- 17436503
TI  - [A clinical, histological, and biochemical study of ovarian arrhenoblastomas:
      with reference to one case].
AB  - The authors review the literature in relation to a detailed study of an ovarian
      arrhenoblastoma operated on in a young patient who subsequently became pregnant
      twice, one of these pregnancies developing to full term. This review makes it
      possible to formulate certain anatomopathological ideas, and above all makes it
      clear that complete endocrine studies are infrequently carried out. It has been
      shown in cases of arrhenoblastoma that some of the anomalies of steroidogenesis
      are secondary to the enzyme disorders, the impression being that, with this kind
      of tumour, the tumour parenchyma begins to secrete like a normal testicle.

PMID- 17436504
TI  - [Lesions associated with uterine fibromas: with reference to 207 cases].
AB  - With reference to 207 observations of lesions associated with uterine fibronias.
      the authors have tried to discover a distinct anatomo-pathological entity.
      Associated lesions are found in 31 percent of cases. and this frequency should be
      particularly noted, when the classical view emphasizes particularly the
      occurrence of complications. The lesions found in association with this type of
      fibroma are listed below in order of frequency of occurrence: infectious lesions,
      ovarian dystrophies, hormonal disorders, benign or malignant tumoral lesions, and
      endometriosis. Attempts at pre-operative diagnosis have been rather
      disappointing, as only 41 percent of the cases have been diagnosed. The presence
      of these associated lesions leads more readily to the use of surgery but it is
      not easy to determine whether this is because of the existence of the lesions or
      because they are misunderstood. if the associated lesions are diagnosed before
      the operation, medical treatment of the lesions, particularly in the case of
      infectious lesions or endometriosis, does not avoid the need for surgery but
      often make it easier.

PMID- 17436505
TI  - [The pathology of the stump of the uterine cervix].
AB  - With reference to 70 patients, the authors studied the pathology of the stump of
      the cervix left after subtotal hysterectomy. The wide range of disorders
      presented by women after partial hysterectomy included metrorrhagia (44.2 percent
      of cases), pelvic pain, leucorrhoea, cervical pain, and functional disorders
      related to prolapse. Lesions found on the stump of the cervix included: cancer in
      15.7 percent of cases, of which the clinical symptoms were not specific to the
      stump of the cervix: however, the methods of treating such cancers, of the usual
      methods are used, raise complex problems; prolapse was found after subtotal
      hysterectomy in 27.1 percent of cases and the symptomatology was not unusual.
      Here also, the absence of the uterus increases the difficulties of surgery. Thus
      subtotal hysterectomy appears to present more dangers than advantages and, except
      in particular cases, the authors prefer total hysterectomy.

PMID- 17436506
TI  - [Value of placental scintigraphy in the diagnosis and surveillance of hydatid
      moles].

PMID- 17436507
TI  - [Ovarian leiomyomas].

PMID- 17436508
TI  - [First results of feeding newborn infants exclusively with milk ready for use in
      bottles].

PMID- 17436510
TI  - [Systematic screening for uterine cancer by exfoliative cytology: an account of 8
      years activity in the cytology laboratory of the Jules Bordet Institute].
AB  - After 8 years experience of systematic screening for asymptomatic uterine cancer
      in 115 604 cases, the authors report the following conclusions: The cytological
      method is useful because it makes it possible to diagnose 2.2 per cent of
      cancerous lesions in an asymptomatic population. The percentage of false
      positives or false negatives is negligible in a laboratory with well trained
      staff. The disparity between the number of no invasive and invasive cervical
      epitheliomas indicates that a certain percentage of non invasive forms do not
      evolve into the invasive form. The number of cancers discovered has remained
      constant over the years; this could be explained in several ways : insufficient
      effort has been made to organize mass screening; the populations effected by the
      screening campaigns do not represent the high-risk groups (older women and the
      poorer social classes); slowly evolving cervical lesions are more likely to be
      detected than those that develop rapidly and have a less favourable prognosis.
      The efficiency of screening campaigns could be improved by providing better
      information to the public and to the medical profession on the advantages of the
      technique. In the absence of a precise biological definition of the
      intraepithelial cancerous lesion, systematic screening for the so-called
      dysplasic or intraepithelial lesions should be continued and adequate
      conservative treatment must be provided.

PMID- 17436509
TI  - [Ovarian dysgerminoma: clinical signs, assessment, and therapeutic indications,
      with reference to 30 observations].
AB  - Thirty cases of ovarian seminomas in patients aged for the most part between 10
      and 20 years were studied at the Gustave-Roussy Institute between 1957 and 1970.
      In 10 per cent of cases both ovaries were involved. They were revealed by
      menstrual disorders, acute cystic twisting, signs of abdomino-pelvic compression,
      or a change in the general state of health. Lymphograms were made for the 25 most
      recent cases. They showed pathological signs in 35 per cent of cases. The role of
      the lymphogram is of prime importance in the suveillance of nonirradiated
      patients, making it possible for them to have remedial treatment. Surgery ensures
      excision of the tumour and indicates the degree of abdominal extension. During a
      second operation, it is possible to transpose a healthy ovary to avoid
      castration. The methods of ganglion irradiation, which should be systematic, are
      discussed in relation to the results of the operation and of the lymphogram. In
      80 per cent of cases, the patients were alive after two years and slightly more
      than half of them had maintained ovarian function.

PMID- 17436511
TI  - [Premature delivery: with reference to certain etiological data and the role of
      cervico-vaginal infections].
AB  - Premature delivery is by definition, delivery that occurs some time before the
      end of pregnancy. It is important, particularly when considering prevention, to
      concentrate only on the criterion of duration of pregnancy and to measure this as
      accurately as possible with the different methods available. The other
      etiological investigations that have been reported should be analysed critically
      as these have generally been based on measurements of weight; on the basis of
      such data, it is not possible to distinguish clearly between hypotrophy and
      prematurity. Furthermore, the factors that are statistically connected with
      prematurity are not necessarily etiologically important. The author believes that
      a factor that is often not mentioned is of direct and etiological importance:
      cervicovaginal infection, the inflammatory irritation of the endocervical canal
      and of the lower pole of the ovum, starting, by means of reflexes, untimely
      uterine contractions.

PMID- 17436512
TI  - [The use of forceps in a university hospital unit].
AB  - The authors report a series of 400 forceps deliveries practiced between 1 January
      1968 and 30 June 1971, in a university hospital unit. Forceps were used in 3.9
      percent of deliveries; 76.9 percent of cases were practiced on primaparas. The
      authors also note the frequency of narrow pelvis (27.2 percent of cases). The
      principal indication for the use of forceps is fetal distress or arrested
      progress (50 percent). Forceps are most often applied at the level of the vulva
      or in the lower third of the pelvic cavity (44 percent of cases). However, it is
      also noted that 9 percent of the applications were made in the middle third and
      that 4.6 percent of the applications were in the upper third (forceps
      indispensable). Thus the authors challenge the unnecessary use of forceps and
      note several failures (3.5 percent) that led to Caesarian sections, principally
      because of feto-pelvic disproportion. Maternal lesions are more frequent when the
      infant is large, when there is occipito-posterior or occipito-transverse
      presentation and when the pelvis is slightly narrowed. As regards the fetus, in
      400 cases of forceps delivery there was one fetal death connected with the use of
      the instrument itself. Concerning the problem of persistent posterior
      presentation, manual rotation should always be attempted, as instrumental
      rotation is dangerous and should not be used in patients with a narrow pelvis.
      Rotation of the head towards the front is justified by the reduction in maternal
      lesions, although the fetal prognosis remains the same. In the face of these
      statistics, modern obstetrics has evolved and all difficult forceps deliveries
      have been rejected in favour of Caesarian delivery.

PMID- 17436513
TI  - [Applications of the quantitative determination of alpha-fetoprotein in
      obstetrics].
AB  - Mancini's technique of simple radial immunodiffusion was used in a study of the
      alpha-fetoprotein (AFP) content of the amniotic fluid (327 samples), the cord
      blood (100 samples) and the blood of the newborn infant (28 samples) in the days
      following birth. The tests for AFP were positive in 26 samples of amniotic fluid:
      19 of them were from pregnancies of less than 25 weeks (the levels of AFP varied
      between 1 and 4.7 mg/100 ml) and 7 were from pregnancies in which grave fetal
      distress was followed by death of the fetus in utero (levels of AFP varied
      between 1.3 and 22 mg/100 ml). Fetal distress was connected with Rhesus
      incompatibility in 3 cases, with a toxaemic syndrome in one case, and was
      unexplained in the other cases. Analysis of AFP levels in the cord blood of
      newborn infants of gestational ages between 33 and 42 weeks did not show a close
      relation with gestational age because of large, individual differences. There was
      a better correlation with the birthweight of the infant. The fall in the serum
      level of AFP was followed in 17 newborn infants during the post-natal period. The
      decrease in the level of AFP was about 50 percent by the 5th day and 90 percent
      by the 9th day after birth.

PMID- 17436514
TI  - [Search for anti-HL-A antibodies in the amniotic fluid].
AB  - Eighty-two samples of amniotic fluid, taken at the moment of delivery, were
      studied in search for anti-HL-A antibodies. A positive reaction to the
      lymphocytotoxicity technique was obtained with 18 of the samples. Only 1 of them,
      a sample from an abortion at the 17th week contained anti-HL-A antibodies; the
      other 17 seemed to contain a nonspecific cytotoxic factor.

PMID- 17436515
TI  - [Ethynodiol diacetate in the treatment of pelvi-genital endometriosis].

PMID- 17436516
TI  - Phytoremediation of soil contaminated with cadmium and/or 2,4,6-trinitrotoluene.
AB  - Phytotoxicity, microbial activity, plant uptake and microbial degradation were
      examined using Rumex crispus in TNT and/or cadmium contaminated columns (TNT: 100
      mg/kg of soil and Cd: 10 mg/kg of soil). The growth of plants was significantly
      inhibited by TNT, but not by Cd. The microbial activity was highly increased by
      plant root growth, decreased by Cd, and slightly reduced by TNT. The plant uptake
      of Cd was relatively well in Cd-contaminated column, but lowered by TNT in TNT+Cd
      contaminated column. The microbial degradation of TNT occurred much faster in
      planted columns than in unplanted columns with minor effect of Cd (less 2-ADNT
      was produced). Therefore, it may be effective to treat TNT first and then Cd
      using phytoremediation in the TNT plus Cd contaminated sites.

PMID- 17436518
TI  - Isolation of a new heterotrophic nitrifying Bacillus sp. strain.
AB  - A heterotrophic nitrifier, named Bacillus sp. LY, was newly isolated from a
      membrane bioreactor (MBR). Bacillus sp. LY could utilize the organic carbon as
      the source of assimilation when it grew on glucose and ammonium chloride medium
      companying the formation of oxidized-nitrogen. It also could denitrify nitrate
      while nitrification. After 24 days incubation, the removal efficiencies of the
      COD and TN by Bacillus sp. LY were 71.7% and 61.2%, respectively. The
      phylogenetic analysis of Bacillus sp. LY was performed and the phylogenetic tree
      of Bacillus sp. LY and the neighbouring nitrifiers was given. Bacillus sp. LY
      could become a new bacterial resource for heterotrophic nitrification and might
      play a bioremediation role for nutrient removal.

PMID- 17436517
TI  - Degradation of microcystins by adsorbed bacteria on a granular active carbon
      (GAC) filter during the water treatment process.
AB  - The degradation of microcystin by adsorbed bacteria on GAC (granular active
      carbon) filter from a water treatment facility was investigated. Dominant
      bacteria isolated from GAC were indigenous microorganisms, Psuedomonas sp. and
      Flavobacterium sp. The direct exposure of dominant GAC bacteria to microcystins
      resulted in a significant reduction of microcystin levels in both shaking and
      static conditions (t-test; p < 0.01). In bacteria-treatments, the half-life of
      microcystin was 2.6-3.5 days in both conditions. Based on this result,
      approximately 9-10 days would be estimated for 90% or up to 18-21 days of 99% of
      toxin to be degraded. This biological degradation by the GAC bacteria in
      combination with existing purification systems has potential to increase the
      efficiency of water purification.

PMID- 17436519
TI  - Acute toxicity and induced weight changes in laboratory tests with Mn and Cu
      against Tilapia guineensis (Dumeril) and Tympanotonus fuscatus (Linne).
AB  - The acute toxicity of Mn and Cu against Tilapia guineensis and Tympanotonus
      fuscatus and the sub-lethal effects of the metals on weight changes were
      investigated in laboratory experiments employing standard bioassay techniques.
      Based on 96 hr LC50 values, copper was more toxic than manganese to either test
      animal by several orders of magnitude. Against either test metal, T. guineensis
      was remarkably more susceptible than T. fuscatus. At sub-lethal concentrations,
      particularly the two highest concentrations tested (0.016 and 0.03 mg Cu L(-1),
      23.0 and 46.0 mg Mn I(-1)), both metals adversely affected the test species by
      bringing about reduced weight gains or weight loss in exposed animals compared to
      untreated controls at the end of the test periods. The implications of these
      findings for ecosystem viability and management are discussed.

PMID- 17436520
TI  - Use of tactile cues by Notiosorex crawfordi (Insectivora) in response to
      topographical features in the environment.
AB  - The present studies were conducted on the ability of males of the gray shrew,
      Notiosorex crawfordi to use tactile cues to detect and respond to changes in
      topographical features of their environment. The animals were videotaped,
      digitized, and analyzed through video recordings. All subjects showed habituation
      (decrease in distance traveled) to arena conditions, followed by dishabituation
      when positions of the blocks were changed. Intact (INT) and sham controls (SHC)
      shrews traveled significantly greater distances and showed higher exploration
      velocities as compared to animals with shaved vibrissae (SHV). Results provide
      empirical evidence that N. crawfordi can effectively use tactile cues to detect
      and respond to changes in its environment.

PMID- 17436521
TI  - Causes of the 1998 Bartin river flood in Western Black Sea region of Turkey.
AB  - A vast flood in the Western Black Sea region of Turkey in May 1998 caused great
      loss of life and significant damage. Communication network, transportation, and
      construction cost of the disaster was estimated around US $500 million. Since
      flood area was relatively large, only Bartin river watershed were analysed and
      investigated within the scope of this study. It is very common having intense
      summer showers, which results in floods and landslides in the region. Land use
      changes in Turkey are rapid; therefore, actual land use format and its recent
      change were determined using remote sensing. Geographic Information System (GIS)
      was employed to evaluate the data collected in the area. Prolonged rainfall on
      saturated soil by antecedent rainfall; misuse of land both in upper and lower
      watersheds are main reasons affecting the formation of such a flood in Bartin
      river watershed.

PMID- 17436522
TI  - A biodiversity approach to check Parthenium hysterophorus L.
AB  - Data collected during our on-going studies on the phytodiversity in the Upper
      Bari Doab Region of Punjab, show an inverse relationship between the level of
      phytodiversity and incidence of the congress grass-Parthenium hysterophorus. The
      open vegetation at Khiala Khurd (31 degrees -33' N-74 degrees .18' E), a site
      typical of the whole region, has a Shannon-Weaver index value of 2.544, which is
      fairly good for any dry tropical area. At this site the weed has an insignificant
      presence (IVI = 0.834%). In contrast, at Fatahpur (31 degrees .33' N-74 degrees
      .21' E), a site bereft of vegetation, it is the dominant species with an IVI of
      79.1%. The corollary emerges that restoration of a natural cover of vegetation is
      the best strategy to check the weed. However, for replantation, the choice of
      species depends on the combination of climatic and edaphic factors obtaining at a
      location.

PMID- 17436523
TI  - Biochemical changes in serum, lung, heart and spleen tissues of mice exposed to
      sub-acute toxic inhalation of mosquito repellent mat vapour.
AB  - The toxicity of sub-acute inhalation of mosquito repellent mat vapour exposure 3
      hr daily, either for a duration of 15 days (Group II) or for 30 days (Group III)
      on biochemical parameters in serum and vital organs was evaluated in mice. The
      control animals were exposed to ambient air 3 hr daily, either for 15 days [Group
      I (a)] or 30 days [Group I (b)]. In both the Group II and Group III exposure
      studies, elevation in the activity of aspartate transaminase (AST) and alanine
      transaminase (ALT) was observed in the serum and heart tissue and a decrease in
      their activity in lung and spleen tissue. This biochemical lesion indicates that
      exposure to mat vapour is capable of interfering with the metabolism of non
      essential amino acids and induce cellular damage in the tissues. The elevation in
      the activity of AST along with that of lactate dehydrogenase (LDH) observed in
      serum and heart tissue in Group II and III studies indicate that exposure to mat
      vapour is capable of inducing changes in the myocardial function. The elevation
      in the activity of alkaline phosphatase (ALP) in serum and a decrease in its
      activity in lung and heart tissue of mice exposed to mat vapour for 30 days
      (Group III) observed in this study denotes that mat vapour could interfere with
      various metabolic functions to induce derangements at cellular level. Inhalation
      of hitherto unidentified volatile chemicals emanated from mosquito repellent mat,
      may contribute as stress factors may contribute as in an indoor environment to
      produce above mentioned biochemical lesions in vital organs.

PMID- 17436524
TI  - Morphological and biochemical studies on the different developmental stages of a
      fresh water snail, Lymnaea stagnalis (Lymnaeidae) after treatment with some
      pesticides.
AB  - In the present study when the egg masses of Lymnaea stagnalis showing different
      developmental stages were introduced with the sub lethal concentrations of baygon
      and nuvan from cleavage to before hatching stages exhibited the development
      arrest in most of the egg capsules due to deviation in protein fractions in the
      corresponding development stages in comparison to control groups resulted into
      high percentage of mortality and low percentage of hatchability in treated
      groups. Another potent cause of low percentage of hatchability of young snails
      from their corresponding egg capsules was the phenomenon of polyembryony in nuvan
      treated egg masses which showed the high rate of mortality due to the lack of
      metabolites for their progressive development in comparison to control groups.
      Teratogenesis and deformities in larval stages were also observed in most of the
      egg capsules which could be correlated with the depletion of most of the protein
      fractions in the present investigation.

PMID- 17436525
TI  - Effects of light on the feedback control of GA-20 oxidase gene homolog in
      DongJinByeo seedlings.
AB  - The effects of gibberellin (GA) on the expression of GA-20 oxidase gene homolog
      were examined in light-grown seedlings and dark-grown seedlings of DongJinByeo.
      The growth rates of the stems of etiolated seedlings were faster than those of
      green seedlings. However, upon addition of GA to these seedlings, the stem growth
      rates of green seedlings were faster than those of etiolated seedlings. To
      understand the molecular mechanism of GA gene regulation in DongJinByeo, total
      RNA from DongJinByeo was hybridized with cDNA of GA-20 oxidase gene homolog.
      Greater accumulation of transcript of GA-20 oxidase gene homolog was observed in
      green seedlings than in etiolated seedlings. However, upon addition of GA, higher
      accumulation of the gene transcript was found in etiolated seedlings than in
      green seedlings, indicating that expression of the transcript of GA-20 oxidase
      gene homolog might be inhibited by light. These results suggest that light might
      regulate feedback control of the transcript of GA-20 oxidase gene homolog in
      DongJinByeo.

PMID- 17436526
TI  - Effect of railway engines emission on the micromorphology of some field plants.
AB  - Plant species as indicator is the most common method used to indicate the effects
      of pollution on plants. However, the present study explores the usage of
      micromorphological parameters of the plant species as the indicators. The plants
      selected for the present studies included Croton bonplandianum, Cannabis sativa
      and Calotropis procera. The parameters examined were (1) abnormalities of
      stomata, (2) number of stomata per unit area, (3) number of epidermal cells per
      unit area, (4) stomatal index. The present studies on these field plants revealed
      that diesel engines emission caused appreciable changes in the number of
      epidermal cells and stomata per unit area. Plants of all the three genera growing
      very close to the railway tracks displayed an adverse effect on these numbers.

PMID- 17436527
TI  - Age and growth patterns in Channa marulius from Harike Wetland (A Ramsar site),
      Punjab, India.
AB  - Scale samples of Channa marulius were collected and studied for age determination
      and calculation of growth parameters. The fish were sampled from Harike Wetland
      during 1998 to 1999. Linear relationship with a high degree of correlation was
      observed between total fish length and the lateral scale radius. Age
      determination studies revealed 5 age groups. The harvestable size falls just
      below the 2nd year. The regression equation is given. Various growth parameters
      indicate a hardy nature of the fish and the suitability of habitat ecology for
      its optimum growth.

PMID- 17436528
TI  - Accumulation of heavy metals (Cd, Cr, Cu, Ni and Zn) in Raphanus sativus L. and
      Spinacia oleracea L. plants irrigated with industrial effluent.
AB  - Effluent from electroplating industry contains various heavy metals like Cd, Cr,
      Cu, Ni and Zn, which are used in electroplating process of industry. Effluent was
      slightly greenish in colour and pungent in odour. Physico-chemical properties
      like total suspended solids (TSS), total solids (TS), alkalinity, Biological
      oxygen demand (BOD), and Chemical oxygen demand (COD) showed higher values in
      effluent with high metal contents like Cd, 0.013; Cr, 0.093; Ni, 0.935 and Zn
      4.76 mg l(-1). plants of S. oleracea and R. sativus were raised in uncontaminated
      alluvial soil of Lucknow by soil pot culture method and irrigated with industrial
      effluent, showed visual toxic symptoms like stunted growth, necrosis followed by
      chlorosis in leaves and finally death of the plants. Severity of toxicity was
      less in plants treated with diluted effluent (50%). High accumulation of Cr,
      302.0; Cu, 81.2; Ni, 155.1 and Zn 146.8 microg g(-1) dry weight in S. oleracea
      and Cr, 198.0; Cu, 41.0; Ni, 84.3 and Zn, 140.2 microg g(-1) dry weight in R.
      sativus were determined. Tissue concentration of metals and toxic effects was
      more in S. oleracea plants. The tissue concentration of metals showed much higher
      values in treated plants than that of their respective control.

PMID- 17436529
TI  - Toxicity of industrial wastewater to the aquatic plant Lemna minor L.
AB  - Toxicity evaluation of industrial wastewater has been done by using bioassay
      system of an aquatic plant Lemna minor at different time intervals. Growth
      inhibition was measured as reduction in fresh and dry weight in industrial
      wastewater and sewage water, exposed L. minor plants. Results of fresh and dry
      weight indicate significant decrease in industrial wastewater and sewage
      wastewater during the different seasons of the year. At 72 and 96 hr of
      industrial wastewater exposure, decrease in chlorophyll content was significant
      in comparison to control. Decrease in total protein content was 32.5%, 14.7% and
      30.6% at 96 hr of exposure in industrial wastewater in premonsoon, monsoon and
      postmonsoon season. Exposure of industrial wastewater to L. minor shows that it
      is a highly sensitive plant to the pollutants present in industrial wastewater.

PMID- 17436530
TI  - Nickel induced histopathological changes in the different tissues of freshwater
      fish, Hypophthalmichthys molitrix (Valenciennes).
AB  - Nickel chloride, heavy metal widely used in industries was investigated in the
      present study for histopathological studies in silver carp (Hypophthalmichthys
      molitrix). Fish were exposed for 10, 20 and 30 days in sublethal concentration of
      nickel 5.7 mg/l. The histopathological changes were studied in the gill, liver,
      intestine and kidney of the nickel treated freshwater fish H. molitrix. The
      nickel showed a tissue specific alteration in the tissues. Mucus proliferation,
      fusion of the gill lamellae and hypertrophy of gill tissues were observed. Lack
      of normal palisade arrangement was followed by necrosis in hepatocytes.
      Degeneration of blood vessels, vacuolation, hypertrophy, pyknotic nuclei and
      lesion were observed in liver tissues. Degeneration of tubular cells, hyperplasia
      was observed in kidney tissues.

PMID- 17436532
TI  - Effect of chromium on protein metabolism of fresh water mussel, Lamellidens
      marginalis.
AB  - Effect of sub-lethal concentration of chromium was studied on the protein
      metabolism in adductor muscle, gill and mantle tissues of fresh water mussel,
      Lamellidens marginalis. Total proteins and RNA showed a decrease while free amino
      acids and protease activity showed an increase. Alanine and Aspartate
      aminotransferase activities showed an increase, while GDH activity showed a
      decrease. It may be suggested that the proteins are degraded and the amino acids
      are incorporated into TCA cycle to augment the energy needs of the organism due
      to chromium toxicity.

PMID- 17436531
TI  - Role of Tribulus terrestris (Linn.) (Zygophyllacea) against mercuric chloride
      induced nephrotoxicity in mice, Mus musculus (Linn.).
AB  - The present study investigates the influence of methanolic fraction (MF) of
      Tribulus terrestris fruit extract on the kidney tissues of mercury intoxicated
      mice, Mus musculus. At median-lethal dose of mercuric chloride (12.9 mg/kg body
      weight), the whole kidney tissue showed an increased level of lipid peroxidation
      (LPO), glutathione peroxidase (GPx) activities and simultaneously a decreased
      level of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH).
      These parameters reached to near normal after administration of fruit extracts of
      T. terrestris for 7 days. The results suggested that the oral administration of
      methanolic fraction of Tribulus terrestris fruit extract at dose 6 mg/kg body
      weight provided protection against the mercuric chloride induced toxicity in the
      mice.

PMID- 17436533
TI  - Biodegradation of pulp and paper mill effluent using anaerobic followed by
      aerobic digestion.
AB  - An experimental study was carried to find out the degradability of black liquor
      of pulp and paper mill wastewater for biomethanogenesis in continuous stirred
      tank reactor (CSTR) and followed by activated sludge process (ASP). Continuous
      stirred tank reactor was used in present study for anaerobic digestion of black
      liquor, while completely mixed activated sludge system was used for aerobic
      digestion. A maximum methane production was found up to 430 ml/day, chemical
      oxygen demand was reduced up to 64% and total volatile fatty acid increased up to
      1500 mg/l from 975 mg/l at 7.3 pH, 37 degrees C temperature and 8 days hydraulic
      retention time during anaerobic digestion. In activated sludge process (aerobic
      digestion) chemical oxygen demand and biological oxygen demand reduction were 81%
      and 86% respectively at 72 hr hydraulic retention time.

PMID- 17436534
TI  - Profile of noise pollution in Lucknow city and its impact on environment.
AB  - Automobiles, construction, festivals, factories, stations, diesel shades, garages
      and workshops are sources of noise. Vehicles are increasing enormously beyond the
      carrying capacity of the road. Study was carried out at 12 locations with sound
      level meter to assess day time and night time noise levels of Lucknow city. In
      residential areas, noise ranged between 67.7 to 78.9 and 52.9 to 56.4; in
      commercial cum traffic areas 74.8 to 84.2 and 68.2 to 74.9 and in industrial
      areas 76.9-77.2 and 72.2-73.1 dB(A) during day and night time respectively.
      Values were higher than their prescribed standards which may pose a significant
      impact on quality of life.

PMID- 17436535
TI  - Interactive effect of metal ions over exponential growth period of microalgal
      cells.
AB  - The interactive effect of metal ions namely chromium and iron has been studied
      under controlled conditions on the diazotropic cyanobacterium Hapalosiphon
      stuhlmannii and the photosynthetic green alga Scenedesmus quadricauda over the
      exponential growth period of the cells. The work describes by employing an
      exponential cell growth model, the effect of metal ions both individually and in
      combination, on the physiological and biochemical characteristics e.g. dry
      weight, chlorophylls, carotenoid and protein content of the cells over the
      concentration range of 0.1-3.0:0.2-16.0 microg/ml of Cr:Fe. The results reveal
      that the interactive effect on the dry weight, chlorophyll and protein content of
      both the algal cells was antagonistic at the bimetallic concentrations of
      0.1:16.0, 3.0:0.2 and 3.0:16.0 microg/ml but the interaction on the protein
      content of both the cells was synergistic at 0.1:0.2 microg/ml of Cr:Fe. Further
      the degree of antagonism on dry weight was higher in H. stuhlmannii than in S.
      quadricauda. The degree of antagonism varied with the bimetallic concentrations
      and was generally lower at the higher metal concentrations. The antagonistic
      behavior was considered to be due to adsorption of one of the metals hindering
      the sorption of the other and the synergistic effect, due to adsorption of one
      enhancing the permeability to the other metal. The varied interactions were
      possibly due to the formation of metal complexes with the microalgal exudes.

PMID- 17436536
TI  - Biological monitoring of roadside plants exposed to vehicular pollution in
      Jalgaon city.
AB  - Experiments on air and biomonitoring were conducted to evaluate pollution impact
      on the vegetation along the road in Jalgaon City, Maharashtra. The plantation
      along the roads and mainly includes neem (Aadirachta indica), peepal (Ficus
      religiosa), banyan (Ficus benghalensis), almond (Terminalia catapa). For
      biomonitoring, leaf area, total chlorophyll, plant protein were analyzed to study
      the impact of air pollutants. It was observed that vegetation at roadside with
      heavy traffic and markets was much affected by vehicular emission. Significant
      decrease in total chlorophyll and protein content was observed with reduced leaf
      area. It is concluded that plants can be used as indicators for urban air
      pollution, and there is need to protect the roadside plants from air pollution.

PMID- 17436537
TI  - Effect of application of different pesticides to soybean on the soil microflora.
AB  - Pesticide residues contributing to the contamination of soil may influence
      microbial population of the soil and in turn fertility of soil. The present paper
      reports the effect of pesticides applied to soybean i.e. phorate, carbofuran,
      carbosulfan, thiomethoxam, imidacloprid, chlorpyriphos and monocrotophos on soil
      microflora. The viable count of rhizobia and phosphate solubilizing bacteria from
      rhizospheric soil of soybean ranged between 10(7)-10(8) cfu/g soil which was
      comparable to the count of bacteria from untreated (control) soil. No significant
      change in the total viable count of any kind of bacteria due to application of
      pesticides has been found showing their ability to degrade these pesticides.

PMID- 17436538
TI  - Genotype X environment interaction and stability analysis of cotton yield in
      Aegean region of Turkey.
AB  - The objective of this study was to determine genotype X environment (GE)
      interaction and stability of cotton genotypes, and effect of different
      environments on seed cotton yield to understand its adaptation to varying
      environments. Fourteen cotton genotypes were evaluated at four locations across
      Aegean region of Turkey in 1997 and 1998. Genotypes were tested by two stability
      parameters as linear regression coefficient (b) and deviations from regression
      (S2d). Significant differences were observed for the mean yields in the 8
      environments. Mean seed cotton yield ranged from 4.58 to 5.80 t ha(-1). Genotypes
      showed significant interaction with environments. Regression coefficients ranged
      from 0.23 to 1.46, and deviations from regression were significant for only four
      genotypes. It was concluded that three high yielding cotton genotypes SG-1001, SG
      125 and DLP-5409 were found to be stable genotypes.

PMID- 17436539
TI  - Diagnostic analysis of the Lake Uluabat in Turkey.
AB  - Diagnostic analysis of wetlands is an ordered/structured method of examining
      wetland systems to identify their values and constraints for the solution of the
      environmental problems. This study focuses on the diagnostic analysis of Lake
      Uluabat on the feasibility of "Objective Oriented Project Planning (OOPP)"
      approach, created by the United States Agency for International Development
      (USAID) and further improved by the Deutsche Gesellschaft fur Technische
      Zusammenarbeit (GTZ). Negative changes both in water quality and quantity were
      determined as the core problems. The main results were summarized as the water
      pollution and fluctuation in the water level caused by the urban and agricultural
      waste disposals, sedimentation, and overfishing. These negative effects cause
      loss of biodiversity and damage to crops. Disposal control, training, adequate
      regulations, and a centralized control and monitoring authority have been
      proposed to cope with the determined problems.

PMID- 17436540
TI  - Impact of mass bathing during Ardhkumbh on water quality status of river Ganga.
AB  - The study highlighted that mass bathing during Ardhkumbh caused the changes in
      the river water quality and indicated that water is not fit for either drinking
      or bathing purposes. The presence of faecal coliforms in water also hints at the
      potential presence of pathogenic microorganisms, which might cause water borne
      diseases. Although the water was found to be safe with respect to dissolved
      oxygen content, the values of BOD and COD exceeded the maximum permissible limit
      during bathing.

PMID- 17436541
TI  - The effects of Co2+ and Zn2+ on the contents of protein, abscisic acid, proline
      and chlorophyll in bean (Phaseolus vulgaris cv. Strike) seedlings.
AB  - 17-day-old bean plants (Phaseolus vulgaris cv. Strike) were used to analyze the
      effects of Co2+ and Zn2+ on the time course of proline, total protein,
      chlorophyll and abscisic acid (ABA) levels in leaves. Controls, Co2+ and Zn2+
      treated plants were grown for 8 days in Hoagland solution. Samples were taken at
      2 day intervals. Proline, chlorophyll (a+b) and total protein contents of 17 day
      old primary leaves were determined by a spectrophotometer. ABA contents in roots
      and leaves of the seedlings were measured by high-pressure liquid chromatography.
      The presence of Zn2+ and Co2+ significantly increased the ABA contents in roots
      and leaves (p < 0.05 or p < 0.01). The increase of the abscisic acid content in
      the leaves was related to the content of the roots. This was further
      substantiated by enhanced accumulation of proline in the leaves of seedlings
      exposed to zinc and cobalt. The contents of chlorophyll (a+b) and total protein
      decreased with the concentration of both metals (p < 0.05 or p < 0.01). Cobalt
      proved to be comparatively more toxic than zinc.

PMID- 17436542
TI  - Limnological features of Thirumullavaram temple pond of Kollam municipality,
      Kerala.
AB  - Thirumullavaram temple pond associated with Sree Mahavishnu temple is located
      very close to the Arabian sea in Kollam municipality of Kerala. Physicochemical
      characteristics of water and sediment, productivity, plankton count, coliform
      count and correlation coefficients of various parameters were analysed for a
      period of one year from June 1999 to May 2000. It showed that the water
      characteristics such as conductivity, turbidity, colour, pH, total alkalinity,
      chloride, total hardness, silicate, phosphate, nitrate, iron, sodium and
      potassium; primary productivity, plankton count, and sediment characteristics
      such as pH, organic matter, potassium and nitrate registered higher values during
      non-rainy season. Coliform count recorded higher value during monsoon season.
      From the correlation study, it was inferred that several characteristics of
      water, sediment and primary productivity were interrelated. Comparison of water
      characteristics with BIS for drinking and swimming water showed that the pond
      water was mainly contaminated with coliform bacteria. However, the physico
      chemical characteristics indicated that it could be used as a potential water
      source for drinking, swimming and for secondary production after proper
      treatment.

PMID- 17436543
TI  - Biomarkers of monocrotophos in a freshwater fish Channa punctatus (Bloch).
AB  - Activity of a few biomarkers have been investigated on freshwater fish Channa
      punctatus treated with monocrotophos for acute exposure to 18.56 ppm at 96 hr and
      subacute exposure viz. 0.46 ppm, 0.96 ppm and 1.86 ppm for 30 days. Biomarkers
      such as total protein, lipid peroxidation and acetylcholinesterase have been
      measured in different tissues of fish viz. gills, liver, brain and muscles. The
      protein levels were found to be depleted in all the tissues after pesticide
      exposure to lethal and sublethal concentration over the control, where as the
      lipid levels showed an increase under the stress of pesticide monocrotophos. The
      increased lipid level may be due to inhibition of lipase activity and other
      biomarkers of lipid metabolism. A significant inhibition of brain
      acetylcholinesterase (AChE) indicating its effects on nervous system have also
      been observed. These parameters can be used as biomarkers to predict the early
      toxicity of monocrotophos added to aquatic ecosystem.

PMID- 17436544
TI  - Ascorbic acid levels in the proglottides of cestode parasite Avitellina lahorea
      (Woodland, 1972) and host serum (sheep) in relation to their sexual maturity.
AB  - The ascorbic acid level was highest in immature proglottides and lowest in gravid
      proglottides of Avitellina lahorea, the gut parasite of sheep. The ascorbic acid
      content in all the regions of the parasite viz., immature, mature and gravid
      taken together remained higher to the value of the host serum. The above gradient
      between the parasite and the host serum interface suggested its active uptake on
      the part of the parasite.

PMID- 17436545
TI  - Rules for nurse staffing law released.

PMID- 17436546
TI  - Mandatory pain management for nurses: advancing the practice of nurses?

PMID- 17436547
TI  - RNA interference for studying the molecular basis of neuropsychiatric disorders.
AB  - RNA interference (RNAi) is a universal and evolutionarily conserved phenomenon of
      post-transcriptional gene silencing by sequence-specific mRNA degradation, which
      is triggered by short double-stranded RNA. This mechanism can be efficiently
      induced both in vitro and in vivo by expressing target-complementary short
      hairpin RNA (shRNA) from non-viral and viral vectors, or by the application of
      short interfering RNA (siRNA). The design of highly selective and efficacious
      siRNA and shRNA has become commonplace, owing to continuous progress in modeling,
      bioinformatics and chemistry. Thus, RNAi is attractive for use in functional
      genomics, target and pathway validation and, potentially, human therapeutics.
      This review highlights recent findings in the field of RNAi with emphasis on
      neuropsychiatric aspects.

PMID- 17436548
TI  - Taxoids: cancer-fighting compounds from nature.
AB  - This review covers advances in the discovery, preclinical and clinical
      development of potential anticancer agents based upon the diterpenoid taxane
      skeleton. The anticancer properties of approved clinical agents of this class are
      not discussed, but the review documents how, 13 years post-approval of paclitaxel
      (Taxol), the base taxane structure is still utilized as the starting skeleton for
      molecules with improved pharmacological and toxicological properties. Paclitaxel
      may in fact be the first example of a 'tunable' anticancer agent. In addition,
      paclitaxel, and perhaps other taxanes in due course, has activities beyond the
      known antitumor indications, with an example being the use of paclitaxel-coated
      stents in cardiovascular therapies.

PMID- 17436549
TI  - Biomedical research tools from the seabed.
AB  - This review covers the applications of small-molecule and peptidic compounds
      isolated from marine organisms for biomedical research. Enzymes and proteins from
      marine sources are already on the market for biomedical applications, but the use
      of small-molecule biomedical research tools of marine origin is less developed.
      For many studies involving these molecules the ultimate goal is the application
      of small-molecule therapeutics in the clinic, but those that do not succeed in
      the clinic still have clearly defined biological activities, which may be of use
      as biomedical research tools. In other cases, the investigation of marine-derived
      compounds has led directly to the discovery of therapeutics with clinical
      applications. Both as tools and therapeutics, these small-molecule compounds are
      effective for investigating biological processes, and in this review the authors
      have chosen to concentrate on the ability of marine natural products to affect
      membrane processes, ion channels and intracellular processes.

PMID- 17436550
TI  - DARPins: a true alternative to antibodies.
AB  - Designed ankyrin repeat proteins (DARPins) are a promising class of non
      immunoglobulin proteins that can offer advantages over antibodies for target
      binding in drug discovery and drug development. DARPins have been successfully
      used, for example, for the inhibition of kinases, proteases and drug-exporting
      membrane proteins. DARPins specifically targeting the cancer marker HER2 have
      also been generated and were shown to function in both in vitro diagnostics and
      in vivo tumor targeting. DARPins are ideally suited for in vivo imaging or
      delivery of toxins or other therapeutic payloads because of their favorable
      molecular properties, including small size and high stability. The low-cost
      production in bacteria and the rapid generation of many target-specific DARPins
      make the DARPin approach useful for drug discovery. Additionally, DARPins can be
      easily generated in multispecific formats, offering the potential to target an
      effector DARPin to a specific organ or to target multiple receptors with one
      molecule composed of several DARPins.

PMID- 17436551
TI  - Highly sensitive target-based whole-cell antibacterial discovery strategy by
      antisense RNA silencing.
AB  - Examples of drug-resistant bacteria are increasing while the discovery of new
      antibiotics with new mechanisms of action has been essentially nonexistent. The
      antisense-based sensitization of bacterial targets in Staphylococcus aureus is
      one of the new approaches that provides increased sensitivity for the detection
      of target-specific antibiotics and whole-cell screening assays based on
      differential sensitivity of target-depleted strains. The screening of natural
      product extracts using this type of assay designed for condensing enzyme
      (FabH/FabF) targets of the fatty acid biosynthesis pathway led to the discovery
      of a number of target-specific inhibitors including the novel antibiotic
      platensimycin, which has displayed activity against various drug-resistant
      bacteria. The antisense-based discovery strategy, rationale and design of
      screening assays, and the application of such assays for screening of natural
      product extracts and the discovery of fatty acid condensing enzyme inhibitors are
      reviewed in this article.

PMID- 17436552
TI  - Affibody molecules: new protein domains for molecular imaging and targeted tumor
      therapy.
AB  - Molecular imaging shows promise as a useful tool to aid drug discovery and
      development and also to provide important prognostic and predictive diagnostic
      information affecting patient management in the clinic. However, the use of
      molecular imaging diagnostically is not widely adopted, in part due to the lack
      of suitable targeting agents. Affibody molecules are a class of small and very
      stable protein domains, which can be used to selectively address a wide range of
      protein targets. Their small size enables high contrast radionuclide imaging and
      they can be produced by conventional peptide synthesis methods. Their potential
      utility in molecular imaging is highlighted in a large number of animal studies
      using anti-HER2 Affibody tracers and has recently been validated in breast cancer
      patients with HER2-expressing metastases. The therapeutic efficacy of the
      Affibody molecules in this indication was demonstrated in preclinical models
      using a targeted radionuclide as the effector function. This review will focus on
      the recent use of Affibody molecules for molecular imaging and their application
      for radioimmunotherapy.

PMID- 17436553
TI  - The chemistry and biology of cyclotides.
AB  - Cyclotides are mini-proteins with a macrocyclic peptide backbone and cystine-knot
      arrangement of disulfide bonds that makes them exceptionally stable to chemical,
      thermal or enzymatic degradation. They have a diverse range of bioactivities and
      are amenable to chemical synthesis, making them accessible as molecular templates
      for protein engineering and drug design applications. In the last two years,
      methods have been developed for the production of cyclotides using inteins in
      bacterial expression systems and using plant cell cultures, adding to established
      methods based on solid-phase peptide synthesis. The availability of an enhanced
      armory of synthetic methods promises to expand the potential range of cyclotide
      based applications.

PMID- 17436554
TI  - Discovery and development of therapeutic cancer vaccines.
AB  - Over the past century, various efforts have been made to induce the rejection of
      cancerous tissues by the stimulation of an immune reaction, using both non
      specific and antigen-specific strategies. Non-specific approaches attempt to
      augment an immune response in and around the tumor by injecting immune
      stimulating substances, for example, bacterial extracts, cytokines or gene
      therapy agents. Antigen-specific approaches use either the tumor cells themselves
      as a source of antigens or incorporate identified tumor-associated antigens into
      vaccines. This review describes antigen-specific therapeutic cancer vaccines that
      are currently in development.

PMID- 17436555
TI  - New methods for efficient protein production in drug discovery.
AB  - The requirement for high levels of stable and functional proteins remains a
      bottleneck in many processes of modern drug discovery, including the high
      throughput screening for novel active compounds or the determination of protein
      structures. Recently, numerous developments have been made to improve the
      production of soluble and active proteins in heterologous expression systems.
      These include versatile expression vectors, new methods for quick cloning, the
      introduction of novel and/or improved prokaryotic and eukaryotic expression
      systems, and more efficient and faster chromatographic procedures that result in
      highly pure proteins. In addition, several techniques allow the attachment of
      small molecular labels to proteins in a site-specific manner, which can be highly
      useful for various important experimental techniques in current drug discovery.

PMID- 17436556
TI  - Non-linear enzymatic logic in natural product modular mega-synthases and 
      synthetases.
AB  - Modular polyketide synthases and nonribosomal peptide synthetases are giant
      multienzymes that catalyze the assembly of a wide variety of bioactive natural
      products including several important clinical drugs. In simple mechanical terms,
      these systems function as molecular assembly lines, where each domain in the
      multienzyme performs its task once during the assembly process. However, several
      polyketide synthase and nonribosomal peptide synthetase systems have been
      discovered with architectures that suggest a deviation from this assembly line
      mechanistic logic. This article discusses progress toward understanding the
      mechanistic logic underlying such non-linear systems, identifies areas where
      further mechanistic insight into these systems is required and reflects on the
      likely consequences of non-linear enzymatic logic for attempts to genetically
      engineer modular polyketide synthases and nonribosomal peptide synthetases to
      produce analogs of bioactive natural products.

PMID- 17436557
TI  - Identification and removal of immunogenicity in therapeutic proteins.
AB  - The development of anti-therapeutic protein immune responses in patients can be a
      severe complication of treatment with this class of pharmaceuticals. Antibodies
      generated against therapeutic proteins limit the clinical efficacy of these
      agents by neutralizing their biological activity and/or enhancing their
      clearance. An assessment of the propensity of protein therapeutics to elicit
      immune responses in patients is likely to become an essential part of their
      preclinical development. It is clear that CD4+ T-cells are an important factor in
      the development of long-lived, class-switched, high-affinity antitherapeutic
      protein antibodies. The increased risk of immunogenicity that is attributed to
      the presence of T-cell epitopes in therapeutic protein sequences has led to the
      development of a variety of methods for locating T-cell epitopes and identifying
      binding peptide amino acids that are important for interacting with either major
      histocompatibility complex class II molecules or the T-cell receptors.
      Manipulation of these key residues to disrupt these interactions while
      maintaining biological activity can result in modified therapeutic proteins with
      reduced immunogenicity.

PMID- 17436558
TI  - [Integrative parent-infant psychotherapy for early regulatory and relationship
      disorders].
AB  - The author introduces both the concept and practice of Integrative Parent-Infant
      Psychotherapy (IPI-P), a treatment specifically designed for the most frequent
      developmental problems and psychological needs of infants and their parents.
      Based on growing knowledge from interdisciplinary infancy research, both basic
      and clinical, IPI-P has been developed and practised in the "Munich
      Interdisciplinary Research and Intervention Program" for early regulatory and
      relationship disorders since the early nineties. Preverbal parent-infant
      communication represents both the port of entry into the system and the main
      focus of diagnostics, developmental counselling, interaction guidance, or
      psychodynamic psychotherapy of distorted communication and distressed/disordered
      relationships. The method of videomicroanalysis during video-feedback with the
      parent has proven particularly efficient--while observing, reliving and working
      through brief episodes of recorded parent-infant interaction. The author
      illustrates the diagnostic and therapeutic procedures with excerpts from
      psychotherapy of a toddler with an age-specific regulatory disorder in the
      context of severely distressed primary relationships.

PMID- 17436559
TI  - [Factors contributing to the use of seclusion and restraint--a retrospective
      analysis in a Swiss clinic for child and adolescent psychiatry].
AB  - Despite of the inculpatory effects of coercive measures on both patients and
      clinicans, only few publications regarding the influencing factors on the use of
      seclusion and restraint could be found. This study intended to investigate clinic
      and patient-related factors which contribute to increasing und intensified
      incidents of seclusion and restraint. All incidents of coercive measures in a
      Swiss clinic during the years 2002 and 2003 were evaluated restrospectively. Data
      included detailed information about each coercive incident as well as patients
      and personnel involved. Statistics were conducted with SPSS. Adolescent age,
      female gender, previous experiences of violence and diagnoses of the ICD-10
      category F9 and F6 were linked with high frequencies and intensive coercive
      interventions on the side of patient-related factors. Regarding clinic-related
      factors a fairly different handling could be found comparing different wards.
      Besides psychopathological aspects of the patients and structural characteristics
      of the clinic different understandings of disease-management, the nature of the
      therapeutic relations and environmental factors contribute to frequency,
      intensity and kind of coercive measures. A detailed evaluation of the use of
      coercive interventions can help to prevent unnecessary and incriminatory
      violence.

PMID- 17436560
TI  - [Childhood in flux--Part I: Ancient world until modern times].
AB  - Scientific research on childhood constitutes a relatively new field. As we know
      today, there is no other period in our lives that more strongly forms us and our
      culture. Hence, it is surprising that in the past this viewpoint was completely
      different. Until medieval times, a child's life did not count for much, that is,
      as long as the child was not the beneficiary of an inheritance. And even if so,
      social relationships were businesslike, e.g. concerning marriage. J.-J. Rousseau
      (1712-1778) demonstrated the worthlessness of children even in his recognition of
      them: The nature of humans is neither good nor bad, and is hardly different from
      that of animals. Despite Rousseau's idealistic concept of education as a kind of
      identification process for the child, he put his own five children into the
      foundling hospital of Paris; he was bothered by them when writing. Up to the
      beginning of the 19th century, the value of a child was determined by his or her
      ability to work. In the years 1813 to 1814 in Great Britain, 130,000 out of
      213,000 weavers were children under the age of 14. Children had to take part in
      breadwinning at an early age; their character was regarded as being like that of
      an immature adult (i. e., a small barbarian). Specific childlike needs were
      rarely met or even acknowledged by adults.

PMID- 17436561
TI  - [Childhood in flux--Part II: Modern times until today].
AB  - At the end of the 19th century, the Society for the Prevention of Cruelty to
      Children was founded in New York, after a barbarous case of neglect and abuse of
      a girl became public. From then on, children received more and more protection.
      Only in the 1950s were doctors in the USA bound by law to report cases of
      putative physical abuse to officials. In Sweden, physical punishment of children
      has been forbidden since 1989, and in Germany since 2001. The existence of sexual
      abuse of children had been a taboo subject for centuries, even though individual
      attempts to break that taboo were made--e. g., by S. Freud in the theory of
      seduction (Verfuhrungstheorie). Only with the birth of the women's liberation
      movement in the early 1970s has public awareness arisen. Due to the work of J.
      Bowlby in the 1950s, it became clear that children of primates need more than
      air, water and food, namely a relationship between the child and an adult person
      (attachment). To what degree the basic needs of children are being fulfilled in
      Western societies today is still a controversial issue.

PMID- 17436562
TI  - Review. Antioxidant gene therapeutic approaches to normal tissue radioprotection
      and tumor radiosensitization.
AB  - Administration of manganese superoxide dismutase-plasmid liposomes (MnSOD-PL) has
      been demonstrated to provide local radiation protection to the lung, esophagus,
      oral cavity, urinary bladder and intestine. Radiation protection has been shown
      to be mediated in part by MnSOD stabilization of the antioxidant pool including
      glutathione and total thiols within cells and in normal tissues. In experiments
      to determine whether organ-specific radioprotection would also protect orthotopic
      tumors, mice with Lewis lung carcinoma orthotopically placed at the carina or in
      other experiments with mice with cheek pouch placed SCCVII orthotopic squamous
      cell tumors demonstrated paradoxical and beneficial tumor radiosensitization
      following intratracheal or intraoral MnSOD-PL, respectively. The mechanism of
      MnSOD-PL tumor radiosensitization may involve a difference in redox balance
      between tumors and normal tissues. Differences in handling radiation-induced
      oxidative stress between tumors and normal tissues can provide a fundamental
      basis to design new cancer therapeutic agents which can exploit differences
      between normal tissue and tumor mechanisms of handling the oxidative stress of
      ionizing irradiation damage.

PMID- 17436563
TI  - Review. TNF/VEGF cross-talk in chronic inflammation-related cancer initiation and
      progression: an early target in anticancer therapeutic strategy.
AB  - In the last decade a growing body of epidemiological and clinical data has
      emerged to support the concept that longstanding inflammation potentiates or
      promotes tumor development, growth and progression. Among pro-inflammatory gene
      products involved in such interactions are tumor necrosis factor (TNF)-alpha,
      interleukin (IL)-6 and vascular endothelial growth factors (VEGFs), whose
      expression is mainly regulated by the transcription nuclear factor (NF)-kappaB.
      Clinically, several reports have detected abnormally high levels of circulating
      cytokines in cancer patients, and inflammation is currently being investigated as
      a target of anticancer therapies. To date three main groups of antiangiogenic
      drugs approved for clinical use and experimentation can be identified: secreted
      VEGF inhibitors, tyrosine kinase (TK) inhibitors (mainly VEGFR inhibitors) and
      drugs that inhibit angiogenesis with a complex mechanism. More recently, TNF
      alpha antagonists have become available. The first clinical data on anti-TNF
      alpha showed that this drug can be used in cancer patients without major
      sideeffects. Further investigations are needed to understand if anti-TNF-alpha or
      NF-kappaB inhibitors may really represent a novel approach in cancer treatment,
      probably as adjuvant to other therapies, such as anti-angiogenic or cytotoxic
      agents.

PMID- 17436564
TI  - Review. Photooxygenation, photodegradation and antioxidative activity of
      platonin, a cyanine photosensitizing dye.
AB  - Platonin (4,4'-dimethyl-3,3'-di-n-heptyl-8-[2-(4methyl-3-n-heptylthiazole)] -2,2'
      dicarbocyanine diiodine) is one of the photosensitive trithiazolepentamethine
      cyanine dyes. Visible light (VL)-promoted photodegradation products of platonin
      in an aqueous environment were identified as 3-heptyl4-methylthiazoline-2 
      carbaldehyde (1), tetradecane-7-thiol (2), 1-nonene (3), heptylamine (4), 3
      heptyl-4-methyl-2-thiazolone (5), 3-heptyl-4-methyl-2-thiothiazolone (6), 5-[2-(3
      heptyl-4-methylthiazolidene)]-2-penten-l-aldehyde (7), gamma-(3-heptyl-4-methyl-2
      thiazolidene)crotonic acid (8) and 3,5-di (4-methyl-2-thiazolyl)-2,4-pentadienic
      acid (9). The quantum yield of singlet oxygen (1O2 (1deltag)) derived from VL
      promoted platonin formed heptyl and heptyl cation radicals together with the
      photodegradation products described above. In isolated rat hepatocytes, platonin
      was cytotoxic under VL irradiation, whereas non-irradiated platonin was less
      cytotoxic and improved cell viability. The effects of oxygen uptake and cell
      viability of photolysis photoproducts of platonin, 3-heptyl-2,4
      dimethylthiazolium iodide (HDT) and 3-heptyl-4-methylthiazolium iodide (HMT) were
      compared with those of platonin. These compounds, particularly the former, showed
      greater cytotoxicity and brought about less oxygen uptake than the latter.
      Radical-scavenging activities of platonin using an induction period method
      demonstrated that fully oxidized platonin had a stoichiometric factor (n) of 4.
      Platonin was a potent peroxy-radical scavenger. The dual modulation activity of
      platonin as a prooxidant and an antioxidant under VL irradiation was revealed by
      monitoring the oxygen uptake in isolated rat hepatocytes. This
      antioxidant/prooxidant activity of platonin may induce diverse effective
      pharmacological activities in biological systems. In the light of recent
      developments in studies of platonin and related compounds, the VL-promoted
      photooxygenation, photodegradation, antioxidant activity and biological activity
      of platonin are discussed.

PMID- 17436565
TI  - DNA repair mechanisms are involved in the hypoxia-dependent toxicity of NLCQ-1
      (NSC 709257) and its synergistic interaction with alkylating agents.
AB  - BACKGROUND: The hypoxia selective cytotoxin NLCQ-1 significantly potentiates the
      antitumor effect of several alkylating agents in vitro and in vivo. Synergy in
      mice requires administration of NLCQ-1 ca. 1 h before the alkylating agent, a
      fact that may be related to an in vitro hypoxic pretreatment effect. Since NLCQ-1
      targets DNA through weak intercalation, the induction of DNA lesions upon
      reductive metabolism may be a reasonable mechanism that predisposes cells to
      further damage by a subsequent alkylating agent. MATERIALS AND METHODS: To
      indirectly identify such lesions, cell lines defective in specific DNA repair
      genes (EM9 and UV41) and their repair-proficient parental AA8, were exposed to
      NLCQ-1 +/-L-PAM/cisDDP under hypoxic/aerobic conditions and appropriate
      administration routes, and assessed for clonogenicity. Selected comparisons with
      tirapazamine (TPZ) were also performed. RESULTS: EM9 cells, which lack the
      functional XRCC1 gene involved in base excision repair, and thus are unable to
      efficiently repair DNA single-strand breaks (ssbs), were 3.7-fold and 4.5-fold
      more sensitive to NLCQ-1 and TPZ, respectively, than the parental AA8 cells,
      under hypoxic conditions. UV41 cells, which are defective in repairing DNA
      interstrand cross-links (ERCC4/XPF), were 4.5-fold more sensitive than AA8 cells
      to NLCQ-1. In potentiation studies with melphalan or cisplatin, synergy was
      observed in AA8 cells but not in EM9 or UV41 cells, with either NLCQ-I or TPZ.
      CONCLUSION: These results suggest that NLCQ-1 is involved in the formation of DNA
      ssbs and interstrand crosslinks under hypoxic conditions. The synergistic
      interaction of NLCQ-1 with L-PAM or cisDDP is probably due to an enhancement in
      the L-PAM/cisDDP-induced DNA interstrand cross-links, possibly as a result of an
      inhibited repair mechanism of these lesions.

PMID- 17436566
TI  - Predicting the biological activities of 2-methoxyphenol antioxidants: effects of
      dimers.
AB  - Selective cyclooxygenase (COX)-2 inhibitors have attracted much attention in
      relation to the design of non-steroidal anti-inflammatory agents (NSAIDs). The
      relationship between experimentally derived data on the antioxidant capacity,
      cytotoxicity and COX-2 inhibition for a range of 2-methoxyphenols and their
      calculated descriptors was investigated. MATERIALS AND METHODS: Quantitative
      structure-activity relationship (QSAR) studies were performed on a series of 2
      methoxyphenols that act as COX-2 inhibitors using electronic descriptors, such as
      the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular
      orbital (LUMO), ionization potential (IP), chemical hardness (q), and
      electronegativity (chi), which were calculated by the CONFLEXIPM3 method. The
      antioxidant capacity of a range of 2-methoxyphenols was evaluated by 2,2'
      diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, and the anti-peroxy
      radical activity (stoichiometric factor, n) was determined by the induction
      period method in the polymerization of methyl methacrylate (MMA) initiated by
      thermal decomposition of benzoyl peroxide (BPO). The 50% cytotoxic concentration
      (CC50) against human submandibular gland tumor cell line (HSG) was determined by
      the MTT method. RESULTS: Cytotoxicity declined in the order of curcumin >
      dehydrodiisoeugenol > isoeugenol >bis-MMP > eugenol > ferulic acid > 2-methoxy-4
      methylphenol (MMP) > bis-eugenol > bis-ferulic acid. The inhibitory effects on
      LPS-induced COX-2 gene expression in RAW 264.7 cells were determined by Northern
      blot assay. The majority of 2-methoxyphenols studied were COX-2 inhibitors. In
      particular, dehydrodiisoeugenol was a potent inhibitor, followed by bis-ferulic
      acid and curcumin. A linear relationship between anti-DPPH radical activity (log
      1/IC50) and IP for 2-methoxyphenols except for dehydrodiisoeugenol was observed
      (r2=0.768.) The n for methoxyphenols was less than 2 in most cases. A linear
      relationship (r(2)=0.713) between the log (1/CC50) and the r1-term except for
      ferulic acid was observed. COX-2 inhibition, except for hesperetin, was related
      to the chi-term (r(2)=0.685). CONCLUSION: It may be possible to predict the
      mechanism responsible for the biological activities of 2-methoxyphenols.

PMID- 17436567
TI  - Review. Facts and fiction of phytotherapy for prostate cancer: a critical
      assessment of preclinical and clinical data.
AB  - The objective of this work was to substantially review all preclinical and
      clinical data on phytochemicals, such as genistein, lycopene, curcumin,
      epigallocatechin-gallate, and resveratrol, in terms of their effects as a
      potential treatment of prostate cancer. It is known, that prostate cancer
      patients increasingly use complementary and alternative medicines in the hope of
      preventing or curing cancer. The preclinical data for the phytochemicals
      presented in this review show a remarkable efficacy against prostate cancer cells
      in vitro, with molecular targets ranging from cell cycle regulation to induction
      of apoptosis. In addition, well-conducted animal experiments support the belief
      that these substances might have a clinical activity on human cancer. However, it
      is impossible to make definite statements or conclusions on the clinical efficacy
      in cancer patients because of the great variability and differences of the study
      designs, small patient numbers, short treatment duration and lack of a
      standardised drug formulation. Although some results from these clinical studies
      seem encouraging, reliable or long-term data on tumor recurrence, disease
      progression and survival are unknown. At present, there is no convincing clinical
      proof or evidence that the cited phythochemicals might be used in an attempt to
      cure cancer of the prostate.

PMID- 17436568
TI  - Review. Acridine orange could be an innovative anticancer agent under photon
      energy.
AB  - Acridine orange (AO) was extracted as a dye from coal tar over a hundred years
      ago. It has various unique biological activities and has been shown to be a
      useful fluorescent dye specific for DNA and RNA, a pH indicator, photosensitizer,
      antitumor and antimalarial drug, and detector of bacteria and parasites. It has
      recently been found that AO accumulates in musculoskeletal sarcomas and that
      after illumination of the tumors with visible light or irradiation with low-dose
      X-rays, the dye rapidly exerts selective cytocidal effect against the sarcoma
      cells. Therefore, surgery combined with photo- (PDT) or radiodynamic therapy
      (RDT) with AO (AO-PDT and -RDT) has been applied to human musculoskeletal
      sarcomas. The results of a clinical study on the outcome of this therapeutic
      strategy revealed that it yielded better local control and remarkably better limb
      function than wide resectional surgery. Based on our experimental studies, it was
      clarified that AO accumulates in acidic organelles or structures, especially
      lysosomes, depending on the acidity. An enormous number of protons are produced
      in cancer from lactate or CO2 under hypoxic conditions, which are moved into the
      extracellular fluid or lysosomes to maintain the intracellularfluid pH.
      Therefore, AO shows marked accumulation in the acidic lysosomes of cancer cells.
      Photon energy from visible light or X-rays excites the AO accumulated in
      lysosomes; the excited AO emits fluorescence and forms activated oxygen from
      intra-cytoplasmic oxygen. The activated oxygen destroys lysosomes, with the
      released lysosomal enzymes causing rapid death of the cancer cells. On the other
      hand, normal cells can exclude AO quickly because they are not acidic. Thus, AO
      PDT and AO-RDT exhibit strong and selective cytocidal effect against malignant
      tumors. In conclusion, we believe that AO-PDT and AO-RDT exhibit selective
      anticancer cell activity and that AO excited by photon energy has excellent
      potential as an anticancer agent.

PMID- 17436569
TI  - Review. The endoplasmic reticulum: a target for new anticancer drugs.
AB  - In eukaryotic cells, the endoplasmic reticulum (ER) is the principal site for the
      folding and maturation of transmembrane, secretory and ER-resident proteins.
      Functions of the ER are affected by various intracellular and extracellular
      stimuli, which include inhibition of glycosylation, reduction of disulfide bonds,
      calcium depletion from the ER lumen, impairment of protein transport to the
      Golgi, and expression of mutated proteins in the ER. Under ER stress,
      unfolded/misfolded proteins accumulate in the ER lumen, which induces conflicting
      cellular activities: survival and apoptosis. To cope with this stress, cells
      activate intracellular signalling pathways, such as the unfolded protein response
      (UPR) and the ER-associated degradation (ERAD). However, under conditions of
      severe ER stress or when the UPR has been compromised, the cell may be incapable
      of maintaining ER homeostasis, which may eventually activate programmed cell
      death (PCD) pathways. Clinical data support the potential of drugs that inhibit
      the normal functions and homeostasis of the ER and the proteasome in treatment of
      malignancies like cancer. It is therefore reasonable to assume that manipulation
      of ER stress might enhance the efficacy of chemotherapeutic drugs and provide new
      anticancer targets like the ER and the proteasome.

PMID- 17436570
TI  - Synthesis and cytotoxic activity of certain 2,3,4,9-tetrahydrofuro [2,3-b]
      quinolin-3,4-dione and ethyl 2-(substituted aniline) -4-oxo-4,5-dihydrofuran-3
      carboxylate derivatives in murine leukemia WEHI-3 cells.
AB  - A series of 2,3,4,9-tetrahydrofuro[2,3-b]quinolin-3,4-dione and ethyl 2
      (substituted aniline) -4-oxo-4,5-dihydrofuran-3-carboxylate were synthesized and
      evaluated for cytotoxicity on murine leukemia WEHI-3 cells. The cytotoxic effects
      of most compounds tested were dose-dependent and the structure-activity
      relationships indicated that N-substituted benzyl derivatives displayed a
      stronger inhibitory activity against murine leukemia WEHI-3 cells compared to non
      N-substituted benzyl substituted derivatives.

PMID- 17436571
TI  - Review. Comparison of multidrug resistant efflux pumps of cancer and bacterial
      cells with respect to the same inhibitory agents.
AB  - Bacteria and cancer cells develop resistance to more than one agent as a
      consequence of being exposed to ineffective levels of the agent for a prolonged
      period of time. The resistance of these cells is mediated by over-expressed
      efflux pumps that have the ability to extrude a large variety of unrelated
      chemicals. This review discusses the main types of multidrug resistant (MDR)
      efflux systems of bacteria and cancer cells, and shows the similarity of specific
      efflux systems between them with respect to given agents that inhibit efflux,
      thus rendering these cells once more susceptible to agents to which they had
      developed MDR.

PMID- 17436572
TI  - Understanding interactions between and among apoptosis inducing pathways in tumor
      cells.
AB  - It has become increasingly clear that the induction of apoptosis in tumor cells
      can occur by at least three different pathways involving the cell surface
      receptors, the mitochondria and the endoplasmic reticulum. Specific drugs and
      conditions can trigger the apoptotic response via one of the three known
      pathways. What is less clear is how these three pathways can interact
      synergistically or antagonistically to influence a common convergence step
      leading to the programmed cell death. In this report we present data to show that
      fenretinide (a synthetic retinoid) potentiates the apoptotic effects of
      parthenolide (a drug that inhibits the activation of NF-kappa B) and BAY 11-7085
      (an inhibitor of I-kappa B-alpha kinase). This potentiation of apoptosis by
      fenretinide is seen in the p53-deficient, deoxyadenosine-resistant L1210 cells,
      but not in the parental L1210 cells that express a mutant p53. These effects are
      seen at a concentration of fenretinide that have little effect by itself. These
      data strongly suggest that fenretinide activates or inhibits some step or pathway
      that interacts with the inhibition of NF-kappa B activation required for the
      apoptotic response. Since parthenolide, BAY 11-7085 and fenretinide are well
      known drugs in clinical trials, an understanding of the nature of the
      interactions between or among the apoptotic pathways could lead to the design of
      better clinical protocols using these drugs that will promote apoptosis in tumor
      cells.

PMID- 17436573
TI  - Yeast therapy for the treatment of breast cancer: a nude mice model study.
AB  - BACKGROUND: Studies have demonstrated that phagocytosis of yeast induces
      apoptosis in human breast cancer (BC) cells in vitro. Here, the in vivo apoptotic
      activity of the S. cerevisiae against human BC (MCF-7) bearing nude mice was
      investigated. MATERIALS AND METHODS: MCF-7 cells were injected into nude mice.
      Mice were then injected intratumorally with yeast on a weekly basis for 45 days.
      Tumors were excised and analyzed for phagocytosis/apoptosis via histopathological
      staining, electron microscopy (EM), and flow cytometry. RESULTS: The results
      demonstrate the ability of MCF-7 cells to phagocytize yeast and the effectiveness
      of yeast in triggering apoptosis in MCF-7 cells in vivo. Histological sections of
      yeast-treated tumors show extensive tumor apoptosis/fibrosis. EM studies clearly
      show apoptotic MCF-7 cells with nuclear margination and fragmentation. Flow
      cytometry confirmed this result. No noticeable adverse side-effects from the
      yeast treatment were observed. CONCLUSION: S. cerevisiae is a promising anti
      cancer agent that induces significant levels of apoptosis in malignant cells in
      vivo. However, yeast therapy for the treatment of breast cancer has yet to pass
      controlled clinical trials.

PMID- 17436574
TI  - Electromicroscopic observations on gliotoxin-induced apoptosis of cancer cells in
      culture and human cancer xenografts in transplanted SCID mice.
AB  - BACKGROUND: Gliotoxin belongs to a group of compounds produced by fungi, all of
      them having a bridged polysulfide piperazine ring in their chemical structure.
      This internal polysulfide bridge enables them to carry out various biofunctions,
      but so far, the toxicity of these compounds limited them to be used as medicines
      in clinic. However, the toxicities of these compounds are quite different and
      determined by their different part of chemical structures. Therefore, it is still
      possible to find a suitable low toxic compound for drug use. As for anticancer
      drug developing, the first need is to confirm the anticancer activity in vivo.
      MATERIALS AND METHODS: The morphological changes of human breast cancer MCF-7
      cells affected by gliotoxin in culture, and the structural damages of human
      cancer xenograft tissue in SCID mice after intra-tumor injection of gliotoxin
      were observed after histological stain and transmission electromicroscopic
      treatment. The DNA changes of the human colon cancer xenograft were observed in
      1.2% agarose gel electrophoresis. RESULTS: Gliotoxin 1 or 5 microM in medium for
      24 hours induced typical apoptotic structural changes to MCF-7 cells, the cell
      surface membrane showed blebbing clearly. Injection of 1 mg gliotoxin into the
      tumor tissue directly did not induce noticeable side-effects to the host mice but
      induced complete damage of the cell structure, the cell surface membran broken
      down and the components of the nuclei segmented. The whole cancer tissue shrinked
      and finally formed a dark color scab which came off from the skin few days later.
      The cured mice showed no tumor recurrence in the six months following
      observation. The apoptotic DNA damage was also found in human colon cancer
      xenograft C1-2 tissues after gliotoxin was injected inside the tumor tissue.
      CONCLUSION: The anticancer activity of gliotoxin is confirmed in vivo.

PMID- 17436575
TI  - Hepoxilin analogs, PBT-3 and PBT-4, cause apoptosis of Gleevec-resistant K562
      cells in vitro.
AB  - The use of Gleevec in the treatment of leukemia has been widely accepted,
      although resistance to Gleevec is commonly observed. Gleevec represents a new
      direction in the development of target-focused chemotherapeutic agents in cancer.
      Gleevec inhibits the tyrosine kinase activity of Bcr-Abl, which is responsible
      for leukemic cell survival. We have previously shown that PBT-3 (racemic anti
      10(R/S)-hydroxy-11, 12-cyclopropyl-eicosa-5Z, 8Z, 14Z-trienoic acid methyl ester)
      and PBT-4 (racemic syn- 10(R/S)-hydroxy- 11,12-cyclopropyleicosa-5Z 8Z, 14Z
      trienoic acid methyl ester), stable analogs of the hepoxilins, caused apoptosis
      of the human leukemic K562 cell line in vitro and in vivo. We also showed that
      PBTs inhibited the growth of tumours derived from the inoculation of
      immunodeficient mice with K562 cells and that the effect of PBTs was synergistic
      with that of Gleevec. We now show that the effect of PBT-3 and of PBT-4 is
      independent of that of Gleevec, demonstrating that Gleevec-resistant K562 cells
      retain their responsiveness to PBT treatment, resulting in apoptosis. These
      findings provide important information suggesting that the two compounds, PBT and
      Gleevec, can be used together in the treatment of leukemia. The PBTs may provide
      a new platform for the development of apoptotic drugs in cancer.

PMID- 17436576
TI  - Review. Clinical pharmacokinetics of bortezomib.
AB  - This review presents the clinical pharmacokinetics of bortezomib. Aspects
      regarding metabolism, pharmacodynamics and drug interactions are also discussed.

PMID- 17436577
TI  - Expression of caspase-14 reduces tumorigenicity of skin cancer cells.
AB  - BACKGROUND: The green tea polyphenol (-)-epigallocatechin-3-gallate (EGCG)
      possesses anti-carcinogenic properties and was found to induce terminal
      differentiation in epidermal keratinocytes. Caspase-14, a member of the caspase
      family associated with epithelial cell differentiation, planned cell death, and
      barrier formation, is induced by EGCG in normal human epidermal keratinocytes but
      not in cancer cells. MATERIALS AND METHODS: A human epidermoid cancer cell line,
      A431, was co-transfected with a caspase-14-expressing pCMV vector and a GFP/neo
      etpressingpCMVvector. Cell growth and tumorigenicity of the stable transfectant
      were determined in comparison to cells transfected with the control GFP/neo
      expressing pCMV vector. RESULTS: Expression of exogenous caspase-14 led to growth
      inhibition and reduced the tumorigenicity of A431 cells. CONCLUSION: Pending
      future studies, caspase-14 could be used as a novel approach to skin cancer
      therapy via gene delivery systems.

PMID- 17436578
TI  - (-)-Menthol inhibits WEHI-3 leukemia cells in vitro and in vivo.
AB  - (-)-Menthol ([1-alpha]-5-methyl-2-[1-methylethyl]-cyclohexanol), is a widely used
      flavoring ingredient in mouthwash, foods, toothpaste and cigarettes. The studies
      reported here revealed that (-)-menthol induced cytotoxicity against murine
      leukemia WEHI-3 cells in vitro in a dose-dependent manner. The effects of (-)
      menthol on WEHI-3 cells in vivo (BALBIc mice) were also examined, and it was
      observed that the Mac-3 and CD11b markers were decreased, indicating inhibition
      of differentiation of the precursor of macrophage and granulocyte. The weights of
      liver and spleen samples from mice treated with (-)-menthol were found to be
      decreased compared to untreated animals.

PMID- 17436579
TI  - Reinforcement of antitumor effect of Cordyceps sinensis by 2'-deoxycoformycin, an
      adenosine deaminase inhibitor.
AB  - In this study, an attempt was made to elucidate the combined effect of 2'
      deoxycoformycin (DCF), an adenosine deaminase inhibitor, with a water extract of
      Cordyceps sinensis (WECS), on the growth curves of mouse melanoma and lung
      carcinoma cells. Sub-confluent cells were harvested with an EDTA trypsin
      solution, and resuspended to appropriate concentrations in DMEM containing 10%
      fetal bovine serum. Using 1x10(5) cells/2 ml in each well of a 12-well culture
      plate, cells were incubated for 24, 48 and 72 h in the presence of WECS alone, or
      WECS plus DCF in a CO2 incubator at 37 degrees C. Duplicate samples of viable
      cells were enumerated with a Coulter counter. The antitumor effect of WECS on the
      growth curves of tumor cell lines increased over 3-fold in combination with DCF.
      These results suggest that DCF has a remarkable reinforcement effect on the
      antitumor activity of WECS. DCF is a potent adjuvant for WECS.

PMID- 17436580
TI  - Antiangiogenic activity of TZT-1027 (soblidotin) on chick chorioallantoic
      membrane and human umbilical vein endothelial cells.
AB  - BACKGROUND: TZT-1027 (Soblidotin), a microtubule-depolymerizing agent, has
      antivascular activity which disrupts newly formed tumor vasculature. In this
      study, it was investigated whether TZT-1027 has also antiangiogenic activity
      preventing neovascularization. MATERIALS AND METHODS: Antiangiogenic activities
      were evaluated in vivo in a chick embryo chorioallantoic membrane (CAM) assay and
      in vitro in a tube formation assay on human umbilical vein endothelial cells
      (HUVEC). RT-PCR and skimmed milk zymography analyses were performed to clarify
      the involvement of angiogenesis-related proteolytic enzymes and transcription
      factors. RESULTS: TZT-1027 at doses of 0.01 and 0.06 microg/egg showed potent
      antiangiogenic activities in the CAM assay (80% and 100% inhibition,
      respectively), with no lethal toxicity to the chick embryo. TZT-1027 at doses of
      0.01-10 ng/mL prevented tube formation, while 1-100 ng/mL disrupted the preformed
      vascular tube. However, mRNA and protein expression were unchanged. CONCLUSION:
      TZT-1027 showed antiangiogenic activity at lower doses than it exhibited its
      antivascular activity. We believe it would exert its antiangiogenic activity,
      even if kept in a tumor at reduced concentrations to keep its antivascular
      activity to a minimum.

PMID- 17436581
TI  - Fucoxanthin, a natural carotenoid, induces G1 arrest and GADD45 gene expression
      in human cancer cells.
AB  - BACKGROUND: Although the antitumor effects of fucoxanthin are known, the precise
      mechanism of action has yet to be elucidated. MATERIALS AND METHODS: HepG2 and
      DU145 cells were used for these investigations. The effect of fucoxanthin on gene
      expression was assayed using a DNA microarray system. Northern blot and/or
      quantitative RT-PCR were carried out to confirm any changes in gene expression.
      The effect of fucoxanthin on cell cycle progression was analyzed using flow
      cytometry. RNA interference experiments were employed for the GADD45 gene.
      RESULTS: Fucoxanthin markedly induced GADD45A, a cell cycle-related gene, in
      HepG2 and DU145 cells. Concomitant G1 arrest, but not apoptosis, was observed in
      both cell types following treatment with fucoxanthin. The introduction of siRNA
      against GADD45A partially perturbed the induction of Gi arrest by fucoxanthin in
      both cell types. CONCLUSION: Fucoxanthin induced G1 arrest in HepG2 and DU145
      cells. GADD45A may be involved in fucoxanthin-induced G1 arrest.

PMID- 17436582
TI  - Selective toxicity and type of cell death induced by various natural and
      synthetic compounds in oral squamous cell carcinoma.
AB  - This article reviews the selective toxicity and type of cell death induced in
      oral squamous cell carcinoma (OSCC) by hundreds of natural and synthetic
      compounds. Flavonoids, coumarins, tannins, ketones and other synthetic compounds
      showed low to moderate tumor-specific cytotoxicity against human OSCC cell lines
      as compared with normal human oral cells (gingival fibroblast, pulp cell,
      periodontal ligament fibroblast), whereas anthracyclines, nocobactins and cyclic
      alpha, beta-unsaturated compounds showed much higher tumor-specific cytotoxicity.
      No strict relationship was found between the tumor-specific cytotoxicity and
      apoptosis induction. There was a considerable variation in drug-sensitivity among
      5 OSCC cell lines. OSCC cell lines were generally resistant to apoptosis
      induction. The cytotoxic activity of antitumor agents is affected by various
      factors related to the compounds themselves, the cells and their environments.
      Systematization of the relationship between these factors and tumor-specificity
      may contribute in the quest for more active compounds.

PMID- 17436583
TI  - Effects of oral administration of berberine on distribution and metabolism of 2
      aminofluorene in Sprague-Dawley rats.
AB  - The effects of berberine on the in vivo N-acetylation and metabolism of 2
      aminofluorene (2-AF) in bladder, blood, colon, kidney, liver, feces and urine
      samples and brain tissues (cerebrum, cerebellum and pineal gland) of male Sprague
      Dawley rats were investigated. Major metabolites, such as 1-OH-2-AAF, 3-OH-2-AAF,
      8-OH-2-AAF and 9-OH-2-AAF were found in bladder tissues, 1-OH-2-AAF, 5-OH-2-AAF
      and 8-OH-2-AAF were found in blood samples, 1-OH-2-AAF, 3-OH-2-AAF, 5-OH-2-AAF, 8
      OH-2-AAF and 9-OH-2-AAF were found in colon tissues, 1-OH-2-AAF, 3-OH-2-AAF and 9
      OH-2-AAF were found in kidney tissues, 1-OH-2-AAF, 3-OH-2-AAF and 8-OH-2-AAF were
      found in liver tissues, 1-OH-2-AAF, 3-OH-2-AAF, 5-OH-2-AAF, 7-OH-2-AAF, 8-OH-2-AA
      and 9-OH-2-AAF were found in feces samples and 1-OH-2-AAF, 3-OH-2-AAF, 5-OH-2
      AAF, 7-OH-2-AAF, 8-OH-2-AA and 9-OH-2-AAF were also found in urine samples, 1-OH
      2-AAF, 3-OH-2-AAF and 8-OH-2-AAF were found in cerebrum tissues, 1-OH-2-AAF, 3-OH
      2-AAF and 7-OH-2-AAF were found in cerebellum tissues. In the control group,
      however, only 2-AF and 2-AAF were found in pineal gland after rats had been
      orally treated with 2-AF (50 mg/kg) for 24 h. Pre-treatment of male rats with
      berberine (40 mg/kg) 24 h prior to the administration of 2-AF (50 mg/kg), as well
      as the co-administration of berberine and 2-AF led to a decrease in the amounts
      of 3-OH-2-AAF and an increase in the amounts of 8-OH-2-AAF in bladder tissues. In
      blood samples, there were significant decreases of 2-AF, 2-AAF, 1-OH-2-AAF and 8
      OH-2-AAF, after rats were pre-treated with berberine for 24 h before the addition
      of 2-AF. However, co-administration of berberine and 2-AF led to an increase in
      the amounts of 5-OH-2-AAF. In colon tissues, there were significant decreases of
      2-AF, 2-AAF, 1-OH-2-AAF and 8-OH-2-AAF in colon samples after rats were treated
      with berberine for 24 h before the addition of 2-AF. 2-AF, 1-OH-2-AAF, 3-OH-2-AAF
      and 9-OH-2-AAF levels were significantly different between control and the group
      treated with berberine and 2-AF at the same time. In kidney tissues, significant
      decreases of 2-AF and 2-AAF and of 3-OH-2-AAF were observed after rats were
      treated with both compounds separately and simultaneously. However, 24 h
      berberine pre-treatment followed by addition of 2-AF led to significant increase
      of 9-IH-2-AAF. In liver tissues, there were significant decreases of 2-AAF and 1
      OH-2-AAF, after co-administration of berberine and 2-AF. The amounts of 2-AAF, 1
      OH-2-AAF and 3-OH-2-AAF were significantly different between the control and the
      group pretreated with berberine 24 h before the addition of 2-AF. In the feces
      samples, there were significant decreases of 2-AAF, 3-OH-2-AAF, 7-OH-2-AAF, 8-OH
      2-AAF and 9-OH-2-AAF after co-administration of berberine and 2-AF. However, the
      berberine pre-treatment followed by addition of 2-AF led to a significant
      increase of 2-AF, 2-AAF and 1-OH-2-AAF levels. In urine samples, there were
      significant differences of 2-AF, 2-AAF, 1-OH-2-AAF, 3-OH-2-AAF, 5-OH-2-AAF, 8-OH
      2-AAF and 9-OH-2-AAF after the co-treatment. However, berberine treatment
      followed by 2-AF led to significant differences in 1-OH-2-AAF and 5-OH-2-AAF
      levels. In the cerebrum samples, there were significant differences in 1-OH-2-AAF
      and 8-OH-2-AAF after both berberine co-treatment and pre-treatment. In cerebellum
      samples, there were also significant differences in the 1-OH-2-AAF and 3-OH-2-AAF
      levels after both co- and pretreatment. In pineal gland samples, there were
      significant differences in 2-AAF levels after co-treatment with berberine and 2
      AF and 1-OH-2-AAF was also found in both groups. However, berberine pre-treatment
      followed by 2-AF led to different levels of 2-AF and 2-AAF, but not of 3-OH-2
      AAF.

PMID- 17436584
TI  - Effects of sulfhydryl compounds on cancer cell lines: I: N-(2-mercaptopropionyl)
      glycine exerts antiproliferating effects and antagonizes the stimulating effect
      of prolactin on MCF-7 human breast cancer cells.
AB  - The effects of prolactin (PRL) and N-(2-mercaptopropionyl)-glycine (MPG) on the
      growth of MCF-7 human breast cancer cells, and the influence of MPG on PRL
      induced MCF- 7 cell proliferation, when added simultaneously to the culture
      medium, were examined. Prolactin at concentrations of 200 ng/ml - 350 ng/ml
      enhanced the growth of MCF-7 cells, while at lower and higher concentrations its
      action was diminished. MPG alone at concentrations above 2 mM caused a decrease
      in cell proliferation. When PRL and MPG were added simultaneously to the culture
      medium, an inhibitory effect on PRL-induced MCF-7 cell proliferation was
      observed, at concentrations of MPG lower than 2 mM.

PMID- 17436585
TI  - The influence of shark liver oils on normal and transformed mammalian cells in
      culture.
AB  - n3 polyunsaturated fatty acids have been reported to have anti-carcinogenic
      effects on mammalian carcinomas. n3 fatty acids occur in high concentrations in
      marine oils, especially shark liver oils. Several reports have indicated an
      extremely low incidence of cancer in sharks, although other reports indicate
      carcinogenesis in some shark species. It has been hypothesised that n3 fatty
      acids and other components of shark liver oil may exert anti-carcinogenic
      effects. The aim of this study was to assess whether shark liver oil, from four
      Indian Ocean shark species, exerted anti-proliferative effects on transformed and
      normal mammalian cells in culture, and to assess whether the ratio of n3 to n6
      polyunsaturates influenced the results. Neither the shark liver oils themselves,
      nor the ratio of n3 to n6, showed any consistently significant effects with
      either transformed or normal cells.

PMID- 17436586
TI  - Review. Molecular background of chemoresistance in pancreatic cancer.
AB  - The survival data of patients with ductal pancreatic adenocarcinoma are rather
      poor, partly because the disease is frequently diagnosed at an advanced stage,
      partly because it is characterized by a chemoresistant phenotype. Even first-line
      chemotherapeutic drugs result in a modest objective response. This drug
      resistance is attributed to many different, unrelated mechanisms, including
      abnormal membrane receptor transport, ineffective metabolic drug conversion or
      enhanced metabolite inactivation, increased DNA repair and alterations in the
      apoptotic pathways. The role of NF-kappaB, cyclin D1 and stromal factors is also
      emphasized by many groups. The involvement of the ABC-transporters is not a
      universal feature, their alterations are important only in the resistance against
      specific cytostatics. Although several well-known molecular mechanisms have been
      elucidated, our understanding of drug insensitivity is still fragmentary,
      especially because recent microarray studies revealed that hundreds of genes are
      up- or down-regulated in resistant tumor cells, but their exact significance is
      still unclear. The reversal of the drug resistance is an area of intensive
      investigation, but to date, the compounds investigated are effective mainly in
      experimental systems and prospective studies are needed to validate their
      clinical applicability.

PMID- 17436587
TI  - Inhibitory effect of an isopropanolic extract of black cohosh on the invasiveness
      of MDA-mB 231 human breast cancer cells.
AB  - BACKGROUND: The isopropanolic extract of black cohosh (iCR)b has recently been
      reported to exert antiproliferative and apoptosis-inducing effects on estrogen
      receptor-positive MCF-7, as well as estrogen receptor-negative MDA-MB 231 human
      breast cancer cells. To broaden observations, the anti-invasive effects of iCR
      and its two major fractions triterpene glycosides (TTG) and cinnamic acid esters
      (CAE) were tested in highly invasive MDA-MB 231 cells. MATERIALS AND METHODS: The
      effect of drugs upon the invasive potential of MDA-MB231 cells was studied in BD
      Biocoat Matrigel invasion chambers over a period of 24 h. RESULTS: The
      suppression of invasion reached 51.8% at 77.4 microg/ml of iCR, an extract
      concentration where 89% of MDA-MB231 cells were viable. TTG and CAE reduced cell
      invasion by 34% and 25.5%, respectively, at a dose of 5 microg/ml. The motility
      of cells was only moderately reduced. CONCLUSION: In this study iCR was found to
      suppress tumor cell invasion without affecting cell viability. This result
      together with the antiproliferative and apoptosis-inducing effect of iCR suggest
      its use as a secure agent in postmenopausal hormone replacement therapy with
      additional chemopreventive activity.

PMID- 17436588
TI  - Treatments for the activating macrophages that reduces surgical stress and
      postoperative mortalities from bacterial infections and tumor metastases.
AB  - BACKGROUND: Some of the mortalities caused by infectious diseases and/or distant
      metastases following surgery are thought to be due to immunological suppression.
      For this reason, techniques that reduce immunological suppression following
      surgery may reduce mortalities and/or incidences of micrometastases in distant
      organs. MATERIALS AND METHODS: Mice were anesthetized and their peritoneal
      cavities were opened for 30 min. Immunological suppression was estimated by the
      presence of tumor necrosis factor-a (TNF) after injection with OK-432 (dead
      bacterial bodies). The mice were administered with either Staphylococcus aureus
      or cancer cells of Meth A fibrosarcoma. Survival times and lung metastastic foci
      were then observed at 3 weeks. Results were compared for mice with or without
      treatment by OK432 or TNF prior to surgery. RESULTS: While significant
      suppression of TNF production was observed after laparotomy, administration of a
      macrophage-activating agent (TNF or OK-432) 3 h prior to laparotomy prevented
      immune suppression after the laparotomy. Laparotomy increased mortalities from
      bacterial infections and promoted the number of lung metastases. By contrast,
      administration of TNF or OK-432 3 h prior to the laparotomy decreased mortalities
      and metastases after the laparotomy. CONCLUSION: These results suggest that
      appropriate activation of macrophages prior to surgery is a method to reduce some
      of the detrimental effects caused by surgical operations.

PMID- 17436589
TI  - Review. Pro- and anti-angiogenesis effects of resveratrol.
AB  - Resveratrol, a natural polyphenol, has a variety of effects including protection
      against ischemia-reperfusion injury, and antitumor and chemopreventive action
      against malignant tumors. In recent years, resveratrol has been found to exert
      pro-and anti-angiogenic effects, depending on the situation. For example, pro
      angiogenic effects are noted in the peri-infarct myocardium, whereas resveratrol
      inhibits angiogenesis in tumors. In this article, a review of the literature
      concerning both pro-angiogenic and anti-angiogenic effects of resveratrol and the
      underlying mechanisms of its effects on angiogenesis is presented.

PMID- 17436591
TI  - Cell-cycle specificity of sulforaphane-mediated apoptosis in Jurkat T-leukemia
      cells.
AB  - BACKGROUND: Sulforaphane (SFN) is an isothiocyanate that is present in widely
      consumed vegetables. Previous studies have shown that SFN is effective in
      preventing carcinogenesis induced by carcinogens in rodents. Recently it was
      found that SFN could also inhibit cell proliferation and induce apoptosis in
      several tumor cell lines. In the present study, the possible cell-cycle
      specificity of SFN-mediated apoptosis was investigated. MATERIALS AND METHODS:
      Cells were synchronized by thymidine block. Analysis of the cell-cycle and
      apoptosis induction was performed using flow cytometry. RESULTS: Flow cytometric
      assessment of the extent of apoptosis in cells synchronized by thymidine block
      revealed that cells were most sensitive to SFN in the G -phase, less sensitive in
      the G2/M-phase and least sensitive during the S-phase. CONCLUSION: These findings
      suggest that cell vulnerability to SFN-mediated apoptosis is subject to
      regulation by cell-cycle-dependent mechanisms.

PMID- 17436590
TI  - Efficient dual treatment of the hormone-refractory prostate cancer cell line
      DU145 with cetuximab and 1,25-dihydroxyvitamin D3.
AB  - BACKGROUND: Targeting of the epidermal growth factor receptor (EGFR) pathway is a
      promising treatment strategy for aggressive androgen-refractory prostate cancer
      (PCa). The effect of treating the androgen-resistant PCa cell line DU145 with a
      combination of the anti-EGFR drug cetuximab and 1,25-dihydroxyvitamin D3
      (1,25(OH)2D3) was evaluated. MATERIALS AND METHODS: DU145 cells were treated with
      5 nM cetuximab, 100 nM 1,25(OH)2D3 or a combination of both. The effect of the
      treatments on cell growth, cell-cycle and apoptosis was evaluated. RESULTS:
      Single-drug treatments decreased DU145 cell growth by up to 25% and caused a 1.5
      to 1.7-fold increase of apoptosis, but did not affect the cell-cycle
      distribution. However, dual treatment with a combination of cetuximab and
      1,25(OH)2D3 inhibited DU145 cell proliferation by 40%, caused considerable cell
      cycle arrest in the Go/Gl-phase, and enhanced apoptosis by 2.5-fold (compared to
      the control, p < 0. 0001, p <0. 006 and p <0. 0001, respectively). CONCLUSION: A
      combination of cetuximab and 1,25(OH)2D3 efficiently suppresses hormone-resistant
      PCa cell growth and could provide a basis for its clinical application.

PMID- 17436592
TI  - 4- [3,5-bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) induced fas
      expression and activated caspase-3 and -8 in a DLD-1 colon cancer cell line.
AB  - BACKGROUND: 4-[3,5-Bis (trimethylsilyl) benzamido] benzoic acid (TAC-101) is a
      novel retinobenzoic acid derivative which has a specific binding affinity to the
      retinoic acid receptors (RAR)alpha and RARbeta. Using time-dependent FACScan
      analysis, it was observed that TAC-101 induced apoptosis in a DLD-1 human colon
      cancer cell line. In this study, the induction of apoptosis-related proteins and
      the activities of caspases in a DLD-1 cell line under medication with TAC-101
      were investigated. MATERIALS AND METHODS: DLD-1 cells were cultured with
      different concentrations of TAC-101 for 12, 24 and 48 h. The expressions of Fas,
      TNF-R1, DR3, bcl-2, Bax and Bid were measured using a Western blot analysis. The
      activities of caspase-3, -8 and -9 were measured using a colorimetric protease
      assay kit. RESULTS: The Western blot analysis showed that TAC-IO1 had almost no
      effect on the level of Bcl-2, Bax or Bid protein. Although TAC-101 did not change
      the expression of TNF-R1 and DR3, TAC-101 increased the expression of Fas in both
      a time- and a dose-dependent manner. A 3-fold increase in caspase-3 activity and
      a 1.5-fold increase in caspase-8 activity were observed in cells treated with TAC
      101 in comparison to the control cells (p<0.01). CONCLUSION: Our data indicate
      that the death receptor root of the apoptotic signal transduction in DLD-1 cells
      mainly participates in the apoptotic induction of TAC-101. Because the compounds
      inducing apoptotic activity are frequent targets of cancer therapy, TAC-101 may
      be a good candidate for use in the treatment of colon cancer.

PMID- 17436593
TI  - Comparison of new nitrosoureas esters with modified steroidal nucleus for
      cytogenetic and antineoplastic activity.
AB  - Nitrosourea is decomposed under physiological conditions to react with biological
      macromolecules by two mechanisms: alkylation (with proteins and nucleic acids)
      and carbamoylation (with proteins but not nucleic acids). It has been suggested
      that the alkylating action is responsible for the therapeutic effects of
      nitrosoureas, and that the carbamoylation activity leads to toxicity effects. In
      order to reduce systemic toxicity and improve specificity and distribution for
      cancer therapy, 2-haloethyl nitrosourea has been esterified with modified
      steroids, which are used as biological platforms for transporting the alkylating
      agent to the tumor site in a specific manner. The cytogenetic and antineoplastic
      effect were studied of seven newly synthesized esters of N,N-bis(2
      chloroethyl)alanyl carboxyl derivatives with a modified steroidal nucleus
      (compounds 1-7). As a very sensitive indicator of genotoxicity the Sister
      Chromatid Exchange (SCE) assay was used and as a valuable marker of cytostatic
      activity the cell Proliferation Rate Index (PRI) in cultures of normal human
      lymphocytes was used. The order of magnitude of the cytogenetic activity on a
      molar basis (15, 30, 120 microM) of the compounds was 7>>6>3>5>2>4>1. The most
      active compound 7 has an enlarged (seven carbon atoms) A ring modified with a
      lactam group (-NHCO-) with the nitrosourea moiety esterified at position 17 In
      the group of seven substances a correlation was observed between the magnitude of
      SCE response and the depression in PRI (r=-O, 65, p<0.001). According to the
      criterion of activity of National Cancer Institute (NCI), the order of
      antineoplastic activity of compounds on lymphoid L1210 leukemia is 7>6>2>5>4>3>1
      and on lympocytic P388 leukemia cells is 7>2>6>5>4>3>1. The present results are
      in agreement with previous suggestions that the effectiveness in cytogenetic
      activity may well be correlated with antitumor effects [T/C: 248% for the
      compound 7 in 250 mg/kg b.w.; T/C: mean survival time of drug-treated animals (T)
      (excluding long term survivals) vs. corn-oil-treated controls (C)].

PMID- 17436594
TI  - Ethyl 2- [N-p-chlorobenzyl- (2'-methyl)] anilino-4-oxo-4,5-dihydrofuran-3
      carboxylate (JOT01007)induces apoptosis in human cervical cancer Ca Ski cells.
AB  - The cytotoxic effects of a new compound, ethyl 2-[N-p-chlorobenzyl-(2'-methyl)]
      aniline-4-oxo-4,5-dihydrofuran-3-carboxylate (JOT01007) have been tested in mouse
      leukemia WEHI-3 cells. In this study, the mechanisms by which JOT01007 acts on a
      human cervical cancer cell line (Ca Ski) to bring about an increase in the ratio
      of Bax/Bcl-2, reduction of the mitochondrial membrane potential (MMP), increase
      in the levels of cytoplasmic Ca2+, activation of caspases and fragmentation of
      DNA, and apoptosis were investigated. Flow cytometric analysis demonstrated that
      JOT01007 induced a decrease of MMP in Ca Ski cells. JOT01007 induced an increase
      in the level of cytoplasmic Ca2+, which was inhibited by BAPTA (calcium
      chelator), and BAPTA accelerated the MMP reduction, and significantly blocked
      JOT01007-induced apoptosis. Western blotting demonstrated that JOT01007 induced
      an increase in the levels of p53, p2I, cytochrome-c, caspase-3 and Bax, but
      decreased the level of Bcl-2. In conclusion, our data demonstrate that JOT01007
      induced apoptosis occurs via a mitochondria-dependent pathway closely related to
      the level of cytoplasmic Ca2+ in Ca Ski cells.

PMID- 17436595
TI  - Berberine inhibits WEHI-3 leukemia cells in vivo.
AB  - Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects
      including anticancer activities, yet the exact effects on leukemia in vivo are
      unknown. Our previous studies have demonstrated that berberine induced
      cytotoxicity against murine leukemia WEHI-3 cells in vitro in a dose-dependent
      manner. In order to understand the berberine action against leukemia, the effect
      of berberine on WEHI-3 leukemia cells in vivo was studied. The results showed
      that Mac-3 and CD11b markers were reduced, indicating differentiation inhibition
      of the macrophages and granulocytes precursors. There was no affect on the CD14
      marker but the CD19 marker that was indicating the promotion of the
      differentiation of the B-cells precursors. The weights of spleen samples from
      mice treated with berberine were found to be lower when compared to these from
      untreated animals.

PMID- 17436596
TI  - Biological properties of new derivatives of daunorubicin.
AB  - In the search for new derivatives of daunorubicin with high activity and/or the
      ability to overcome the drug resistance barrier of cancer cells, some new analogs
      of amidino-daunorubicin, containing the chiral substituent in the formamidine
      group (-N=CH-N<) at the C-3' position of daunosamine moiety, have been
      synthesized. In order to estimate the influence of the configuration of the
      chiral group on the biological properties of the new derivatives of daunorubicin,
      three chiral amines, namely 1-cyclohexyl-ethylamine, 1-phenylethylamine and N
      methyl-l-phenyl-ethylamine, both R and S isomers and their racemates, were used.
      These new compounds were tested for their cytotoxic activity in vitro against the
      cells of A549, SW707, T47D and HCV29T cancer lines. The resistance index (RI)
      values were obtained using the cells of the sensitive LoVo, MES-SA, HL-60 human
      cancer cell lines, as well as their resistant sublines (LoVo/Dx, MES-SAIDX5 and
      HL-60/MX2, respectively). All obtained derivatives appeared to be able to
      overcome the drug resistance barrier of cancer cells.

PMID- 17436597
TI  - Anticancer effect of a new benzophenanthridine isolated from Zanthoxylum
      madagascariense (Rutaceline).
AB  - Fractionation of the cyclohexane extract from the stem bark powder of Zanthoxylum
      madagascariense led to the isolation of a new benzophenanthridine-type alkaloid,
      hydrochloride of 2,3-methylendioxy-8-hydroxy- 7-methoxy-benzo[C]phenanthridine
      (Rutaceline), characterized on the basis of its spectral data. Rutaceline was
      evaluated for its antiproliferative capacity on the human colorectal
      adenocarcinoma (Caco-2) and the African green monkey kidney (Vero) cell lines.
      The 50% inhibition of cell growth (IC50) obtained after 24 h incubation was
      similar for both cells lines (110-115 microg/ml, i.e. 269-281 microM), but at 48
      h the IC50 value for the Caco-2 cells was lower than for the Vero cells (20
      microg/lml, i.e. 49 microM versus 90 microg/ml, i.e. 220 microM) indicating a
      higher cell growth inhibitory effect on the colon adenocarcinoma cells. At the
      respective IC50 concentrations, Rutaceline did not significantly induce apoptosis
      but induced cell cycle arrest in the GO/G1 phase, as well as a decrease of cells
      in S phase. Rutaceline also induced DNA fragmentation in both cell lines, as
      revealed by agarose gel electrophoresis, and a dose-dependent clastogenic effect
      in both cell lines as revealed by the Comet assay.

PMID- 17436598
TI  - Review. Evidence-based complementary oncology. Innovative approaches to optimize
      standard therapy strategies.
AB  - Cancer diseases demand diagnostic and therapeutic measures with proven quality,
      safety and efficacy. The basis for evaluation is clinical studies representing
      levels I or II (randomized controlled trials (RCT) or epidemiological cohort
      studies) in accordance with recommendations of the Centre for Evidence-based
      Medicine, University of Oxford, UK Regarding these claims, surgery, chemo-, radio
      and hormone therapy have emerged as the gold standard in the treatment of
      carcinomas. These therapies have proven their cancer destructive potencies and
      their curative feasibilities, dependent on the particular cancer entity and
      stage. Complementary therapies are recommended to support and optimize the
      scientifically-based cancer standard treatment. Complementary medicine is
      currently widely debated by the oncological community, because the required
      scientific proof of safety and effectiveness for most of the therapeutic
      approaches has not yet been definitively provided. In the past years, basic
      research and clinical evaluation of defined complementary therapeutic concepts in
      oncology have been intensified in an attempt to integrate these procedures into
      evidence-based medicine. Scientifically-based therapies of complementary medicine
      cannot replace the well studied conventional cancer-destructive therapies such as
      surgery, chemo-, radio- or hormone therapy. Accordingly, they are by no means
      "alternative therapies". Complementary approaches in oncology that are
      recommended as additional to standard cancer destructive therapies claim to
      optimize this therapy. A great body of data emerging from scientifically sound
      clinical trials prove that defined complementary procedures are beneficial for
      the patients.

PMID- 17436599
TI  - Effects of nontoxic heat shock protein 90 inhibitor peptide derivatives on
      reversal of MDR of tumor cells.
AB  - Novel heat shock protein 90 inhibitor peptide derivatives [D- Trp-Phe-D- Trp-Leu
      AMB (1), p-HOPA-D- TrpPhe-D-Trp-Leu-psi(CH2NH)-Leu-NH2 (2), D-Trp-Phe-D-Trp-OH
      (3), Suc-D-Trp-Phe-D-Trp-Leu-AMB (4), D-Tyr-Phe-D-Trp-Leu-AMB (5), D-Arg-D-Trp
      Phe-D-Trp-Leu-Leu-NH2 (6), Leu-psi(CH2NH)-Leu-NH2x2HCl (7), Phe-Trp-Phe-Trp-Leu
      Leu-NH2 (8), Tyr-Trp-Phe-Trp-Leu-Leu-NH2 (9) and Tyr-D- Trp-Phe-D-Trp-Leu-Leu-NH2
      (10)] were synthetized, and their ability to reverse multidrug resistance (MDR)
      was studied. Peptide derivatives 1, 4 and 5, with D-Trp or D-Tyr residues in the
      N-terminal position caused a marked inhibition of MDR in cancer cells. These MDR
      inhibitor compounds and epirubicin were demonstrated to have additive and
      synergistic antiproliferative effects in checkerboard experiments on human MDR1
      gene-transfected mouse lymphoma cells in vitro. It is suggested that the MDR
      reversal effects of these anticancer peptide derivatives, together with their
      antiproliferative effects on lung cancer cells, may open up new horizons in
      cancer chemotherapy.

PMID- 17436600
TI  - Future of infertility treatment.
AB  - The development of techniques to prolong the window of fertility for women has
      the ability to meet the needs of future populations and their delay in
      childbearing. With current techniques of cryopreservation of embryos, oocytes, or
      ovarian tissue, prolongation of fertility with varying success is feasible. In
      the future, rejuvenation of aging oocytes will offer the opportunity for the
      aging women to achieve pregnancy with their own genetic offspring. Production of
      germ cells from embryonic stem cells is another alternative for patient with poor
      or depleted germ cells. Better understanding of the cause of infertility can be
      achieved with new techniques to evaluate the oocytes, spermatozoa, and embryos on
      molecular and genetic levels. With improved understanding of the etiology of
      infertility, treatment will be more effective. With the advance of new drugs and
      surgical equipment, treatment of infertility will become more convenient and
      effective.

PMID- 17436601
TI  - Optimizing the gonadotrophin dose regimen.
AB  - The starting dose of gonadotrophin for controlled ovarian stimulation (COS) or
      ovulation induction (OI) must be individualized and has considerable impact on
      outcomes (pregnancy and adverse events). Five large randomized, controlled trials
      have compared fixed doses of recombinant follicle-stimulating hormone (rFSH) for
      COS for assisted reproductive technology (ART). Among young women, a fixed dosage
      of 200 IU/day (versus 100 IU/day) yielded more oocytes and more transferable
      embryos. Thus, if surplus embryos can be cryopreserved, it could result in a
      higher cumulative pregnancy rate. However, no clear dose-response relationship
      was evident among older women receiving either 150 or 250 IU/day. Another
      randomized, controlled trial showed that a low-dose step-up OI protocol with
      weekly increments of 25 IU/day of rFSH was more effective and more efficient than
      a regimen with 50-IU/day increments. Research to develop a normogram for the
      optimal starting dose of rFSH for individual patients is under way.

PMID- 17436602
TI  - Ovarian stimulation in polycystic ovarian syndrome.
AB  - We tried to overview the various methods of ovulation induction in patients with
      polycystic ovarian syndrome (PCOS), a syndrome that remains a diagnostic and
      therapeutic challenge. Although fertility treatments have been given since the
      early 1960s, there is controversy and a long-standing debate on the treatment of
      choice in these patients, taking into consideration the success rates and
      possible complications. Clomiphene citrate (CC) is still the first drug of
      choice, but new medications, such as metformin and aromatase inhibitor, and new
      protocols like the chromic low dose, are suggested as better alternatives to CC
      treatment. To reach such a conclusion, more prospective randomized control trials
      should be done. Because PCOS contains a verity of fertility and general health
      problems and symptoms, it is of great importance to "tailor" the specific
      treatment to the individual patient.

PMID- 17436603
TI  - Beneficial effects of a higher starting dose of gonadotrophins in some poor
      responders.
AB  - We performed a prospective study to examine the benefits of higher starting dose
      in poor responders to gonadotrophins. One hundred eighty-seven normal responders
      (group 1), 40 poor responders (group 2), and 25 poor responders from group 2
      (group 3) were included in the study. Groups 1 and 2 received 300 IU of metrodin
      HP for 5 days followed by 150 IU of recombinant human follicle-stimulating
      hormone (rhFSH) until the day before hCG. Group 3 received 450 IU of metrodin
      followed by rhFSH as in groups 1 and 2. Number of oocytes retrieved, rates of
      fertilization, implantation, pregnancy, and miscarriage rates were compared
      between the groups. There were no differences between the three groups in the
      fertilization rate. The higher dose of metrodin (450 IU) for 5 days increased the
      number of oocytes retrieved in some patients belonging to group 3 and
      significantly increased (P < 0.01) the implantation and pregnancy rates compared
      with group 2 patients. However, the higher dose of metrodin also increased
      miscarriage rates significantly in group 3 compared with groups 1 and 2 (P <
      0.04). In some poor responders, a higher starting dose of gonadotrophin resulted
      in more oocytes retrieved and led to higher implantation and pregnancy rates and
      a higher miscarriage rate.

PMID- 17436605
TI  - Cryopreservation of embryos by vitrification: current development.
AB  - Vitrification as a cryopreservation method has many primary advantages and
      benefits, such as no ice crystal formation through increased speed of temperature
      conduction, which provides a significant increase in cooling rates. This permits
      the use of less concentrated cryoprotectant agents so that the toxic effect is
      decreased. Additionally, chilling injuries are considerably reduced. Many
      variables in the vitrification process exist that can profoundly influence its
      effectiveness and the potential to improve the survival rates of vitrified cells.
      These include (i) the type and concentration of cryoprotectant (almost every kind
      of cryoprotectant is toxic), (ii) the temperature of the vitrification solution
      at exposure, (iii) the duration of exposure to the final cryoprotectant before
      plunging into LN2, (iv) the type of device that is used for vitrification (which
      influences the size of the vapor coat and cooling rate), and (v) the quality and
      developmental stage of embryos. Increasing the speed of thermal conduction and
      decreasing the concentration of cryoprotectant is an ideal strategy for
      cryostorage of embryos with vitrification methods. However, the actual rate of
      heat transfer during vitrification procedures may vary extremely depending on the
      device used, technical proficiency, and the specific movement at immersion. In
      addition, it is very important to mention that every cell has its own optimal
      cooling rate. To date, the "universal" vitrification protocol has yet to be
      defined. In light of this, it is important for researchers to achieve more
      consistent results from existing protocols and thereby to establish a
      standardized vitrification protocol that can be applied for cryopreservation of
      different developmental stages. Toward this end, it should be noted that
      vitrification protocols are starting to enter the mainstream of human ART.
      Protocols successfully applied for bovine oocytes and embryos have been used
      initially with human oocytes, and initial trials have been undertaken with human
      embryos and blastocysts, with births achieved. Vitrification is relatively
      simple, requires no expensive programmable freezing equipment, and relies on the
      placement of the embryos in a very small volume of vitrification medium that must
      be cooled at extreme rates not obtainable in regular enclosed cryostraws and
      cryovials. The more convenient protocols of ultrarapid freezing and
      vitrification, which eliminate the use of expensive controlled-rate freezers,
      await cross-over from use in other species, and they require validation from more
      extensive experimental study in humans. Despite this, the convenience of
      vitrification will push the development of this technique to higher levels of
      clinical efficiency and use.

PMID- 17436604
TI  - Treatment strategies in assisted reproduction for women of advanced maternal age.
AB  - In a spontaneous menstrual cycle, during the follicular phase, only one follicle
      out of a cohort of 10-20 usually completes maturation and ovulates to release a
      mature oocyte. The aim of ovarian stimulation in assisted reproductive technology
      (ART) protocols is to overcome the selection of a dominant follicle and to allow
      the growth of a cohort of follicles. This strategy leads to an increase in the
      number of oocytes and hence embryos available for transfer, thereby increasing
      the chance of transferring up to three viable embryos. However, the chance of
      pregnancy and also live birth begins to dramatically decline after the age of 35,
      and successful treatment for these patients continues to be a major challenge in
      ART programs. Preimplantation genetic screening studies over the last decade have
      identified a dramatic increase in the rate of aneuploidy as a major contributor
      to the reduction in embryo viability in older patients. It has also been
      demonstrated that women of advanced maternal age may have oocytes that are
      compromised by a significant reduction in the amount of mitochondrial DNA in
      their cytoplasm. The strategies outlined in this review may provide a means of
      augmenting follicular recruitment and cytoplasmic integrity by utilizing
      pharmacogenomics and manipulating endocrinology to improve the prognosis for
      these women. Recent studies indicate that androgen supplementation may be one
      area to explore further. The availability of recombinant human leutinizing
      hormone (rhLH) has made it possible to investigate the role of LH in the
      endocrinology of follicular recruitment: it appears that a defect in the balance
      of LH/ follicle-stimulating hormone (FSH) might be involved in the subtle age
      related decline in follicular recruitment, and patients of older reproductive age
      undergoing ART might benefit from the addition of LH and/or hGH. Further studies
      are required to investigate the physiological mechanisms behind this observation
      and to assess the possible effect of LH and/or hGH supplementation on the age
      related decline in pregnancy rate.

PMID- 17436606
TI  - Implantation in IVF.
AB  - The recent advances in assisted reproduction have made it possible to study and
      interfere in almost every step of the human reproductive process except for
      implantation. The most complex and important step remains in great part unknown.
      Implantation in human has proven to be less efficient compared with other
      species. However, in in vitro fertilization (IVF) patients, it has been evaluated
      to be even poorer. This paper highlights the factors related to infertile
      patients and IVF treatments that can affect implantation and implantation's
      clinical aspects related to these treatments: implantation failure and early
      pregnancy loss.

PMID- 17436607
TI  - Laparoscopic myomectomy for large myomas.
AB  - Uterine fibroids occur in >40% of women today. This paper describes operative
      techniques for the removal of huge fibroids (4-20 cm) laparoscopically, as an
      alternative to laparotomy, while preserving fertility potential. The fibroids
      were removed through circular incisions into the serosa, the raw uterine defects
      are closed by purse-string sutures, and the fibroids are morcellated before
      removal. Blood loss was minimized with vasopressin, and adhesion prevention was
      obtained with dexamethasone and Interceed. All 300 patients in this study had
      their fibroids removed successfully laparoscopically, with minimal blood loss,
      excellent recovery, and without complications.

PMID- 17436608
TI  - How microsurgery can assist in tubal reconstruction.
AB  - Despite the fact that gynecologists were very early users of the operating
      microscope to observe the possible pathology of the cervical mucosa by brilliant
      lighting and magnification, the advent of in vitro fertilization (IVF) seems to
      have stopped this specialty from using the benefits of microsurgery in female
      tubal reconstruction. Now having performed and followed up for at least 2 years
      nearly 1000 microsurgical tubal reconstructions after sterilizations, with an
      endpoint being the birth of a baby in the time following, it is obvious that
      there are real benefits in pursuing these techniques, because no single IVF Unit
      in the world gets even half as many live birth results from their best practices.
      Apart from a genuine 82.7% baby result from all comers, of any child-bearing age
      and "sterilization age," with an ectopic pregnancy rate of <1%, there are the
      benefits of (i) a single procedure, (ii) normal intercourse to become pregnant is
      the way to go, (iii) psychological trauma of the women involved is not a problem,
      and (iv) the next baby after the first is "free." In our opinion, it is sensible
      to scientifically attempt to reconstruct a deliberately blocked tube in the first
      instance because it is healthier (for mother and children), less expensive, more
      satisfying and psychologically acceptable, and is certainly far more reliable in
      its results than any other baby-promoting proceedure now available. It is
      regretted that gynecologists who flocked to workshops teaching microsurgical
      gynecological techniques before IVF was established now do not even seem to
      consider giving the operative reconstruction as a first alternative to their
      couples that come to them with sterilization as the cause of infertility.

PMID- 17436609
TI  - Microsurgery in common cases of male infertility.
AB  - Prior to the advent of microsurgical equipment and techniques, it was rare for
      urologists or other surgeons to produce a full pregnancy as a result of
      reconstructing fine tubal blockages in the male reproductive tract. Perhaps 2% of
      vasectomized men, and a large percent of men born sterile, are desirous of being
      able to start a pregnancy, and so in 1970, I began a research project with new
      equipment to find a reliable way of joining fine body tubes. I found that our
      bodily tubes can be grouped as being three-layered and that their differences lay
      mainly in the kind of inner, individual mucosal cell structure and their type and
      thickness of the muscular layer. The latter was most important, because the
      pressure built up on peristaltic movement waves in extremely small diameter tubes
      can be very high indeed, forcing tubal contents out, and early escape of fluid
      from the anastomotic site will easily occur unless the joining technique is
      designed to specifically prevent this eventuality. Based on this anatomical and
      physiological information, new techniques for reconstruction of the vas deferens
      and the epididymis were perfected. Consecutive personal series of 5000 vaso
      vasostomies and almost 500 epididymo-vasostomies have now been carried out since
      1971 with extraordinary results in baby birth rates-far better than those that
      occurred before microsurgery.

PMID- 17436610
TI  - Varicocele in male factor infertility: role of laparoscopic varicocelectomy.
AB  - Among the causes of male infertility, the varicocele accounts for 40%.
      Videolaparoscopic varicocelectomy was used for the treatment of 800 men as day
      surgery cases. The operation enabled high bilateral ligation, with an average
      operating time of 1.5 hours. Operative difficulties were minor being colon
      adhesions, vascularity, and obesity. There were no complications. Testicular
      biopsies showed permanent damage varying between 1% and > or =70%. The surgery
      was very well accepted because of its convenience, smooth and rapid recovery,
      improved sexual performance, and cost savings. Among the men treated, semen
      parameters improved among 80%; 45% of their wives becoming pregnant. There is
      clearly a role for videolaparoscopic varicocelectomy in the treatment of male
      infertility.

PMID- 17436611
TI  - Alternatives for non-PDE5-I responders in erectile dysfunction patients.
AB  - The management of a patient presenting with erectile dysfunction encompasses the
      classical complete history, physical examination, blood work-up, and radiographic
      or sonographic studies. Often the history directs the treatment toward counseling
      and psychosexual therapy with use of PDE5 inhibitors as the first-line approach.
      When the latter fails, other oral erectogenic drugs, vasoactive injectables,
      creams, or hormone treatment is given based on the work-up. In certain cases of
      vasculogenic etiology, ligation of venous leakers or revascularization of the
      penis may be appropriate. The port of last call is the penile prosthetic implant.
      The implant, however, is an all or none option, requiring surgical destruction of
      the corporal tissue before implantation, and once inserted, it the implant must
      function forever. Explantation because of infection or for other reasons renders
      the patient impotent unless another implant is inserted. The Brindley penile drug
      delivery implant provides a solution that, when no longer needed, can be removed
      and returns the penis to its preimplant status. If a vasoactive drug like
      prostaglandin works, the candidate is deemed suitable. The device uses sodium
      nitroprusside. Through minimal access (day) surgery, the magnitude of which is
      only a stage slightly higher than integumentary surgery and done within 20-30
      minutes, this is an advance that is presented herewith with a full account of the
      components, preoperative preparation, drug filling and refilling, and a step by
      step account of the surgery.

PMID- 17436612
TI  - Malignant and benign thoracic tumors during pregnancy.
AB  - Eight female patients 23-38 years of age are presented who were pregnant and had
      concomitant thoracic tumors. The tumors were of a variety of cell types, both
      malignant and benign, causing chest pain, dyspnea, shock, hemoptysis, and mass
      formation. Surgical intervention, cobalt radiation, and chemotherapy led to
      survival and cure of both the mothers and the children. An aggressive approach is
      recommended.

PMID- 17436613
TI  - Surgical training and practice.
AB  - Surgery has had a long history and rich heritage in its practice and training.
      From a craft based vocation some 500 years ago, it has evolved into a noble
      profession based on science. The remarkable scientific and technological advances
      during the last century have made surgery safer and the quality of life better
      for the patient. However, the cost and quality of health care delivery and public
      expectation are major issues to deal with. The changing face of surgery needs a
      more structured training program and major commitment of trainees and surgeons.
      The challenge for the future surgeon and trainee is to constantly learn new
      skills and competencies including new professionalism to deliver high-quality
      care.

PMID- 17436615
TI  - [Research on the classification of streptomyces strain ZG0429 and purification of
      streptavidin].
AB  - Actinomycete strain ZG0429 with high production of streptavidin was isolated from
      soil samples. Based on the results of morphological, physiological,
      chemotaxonomic characteristics and 16S rRNA analysis, strain ZG0429 was placed
      within the genus Streptomyces and identified as the species Streptomyces
      lavendulae. The production reached 201.0mg/L under our fermentation conditions.
      With the effective system of ammonium-sulfate deposition and gel filtration
      chromatography, streptavidin was successfully purified from the culture
      supernatant with an overall recovery of 76.87% and purity of 97.03% . This study
      illustrates an effective and inexpensive method to produce the aimed protein with
      favorable yield, high purity and desirable activity, so it provides a valuable
      reference for the large-scale industrial production and isolation of
      streptavidin.

PMID- 17436614
TI  - [Isolation, identification, phylogenetic analysis and related properties of a
      pathogen in Silurus meridionalis Chen].
AB  - In October 2005, a large number of adults of Silurus meridionalis Chen died in
      the mud fish farming of Sichuan province. Later, three predominate strains of
      bacteria were isolated from the body of moribund fish. By artificial infection
      tests, strain TWN3 was confirmed to be the pathogen of the disease. Based on the
      characteristics of morphology, physiology and biochemistry tests, TWN3 was
      initially identified as Proteus vulgaris, and its G + C content of DNA is 39.1% .
      After being amplified, the sequence of its 16S rDNA was analyzed in the database
      of NCBI and it showed that TWN3 had the highest similarity to P. vulgaris, with
      99.52% identity. By constructing the molecular phylogenetic dendrogram with
      Minimum Evolution method in Mega3.1, it was revealed that TWN3 was in the same
      branch with P. vulgaris. Based on all the results above, TWN3 is identified as P.
      vulgaris. However, the result of one biochemistry test, growth in KCN, deviates
      from the description in Bergey's Manual of Systematic Bacteriology. With
      reference to the Manual above, Proteus vulgaris is divided into two groups, P.
      vulgaris BG2 and 3. According to the specific biochemical properties, TWN3 is
      classified as a member of P. vulgaris BG3. Relevant tests of biological
      properties were also conducted, which showed that this strain has no haemolysis
      and is sensitive to four kinds of antibiotic such as gentamicin. Moreover, it can
      strongly cause diseases to mice. The research on the growth property of strain
      TWN3 indicated that its growth temperature ranges from 10 degrees C to 43 degrees
      C , optimum 37 degrees C ; growth pH ranges from 4 to 11, optimum 6. Its optimum
      salinity varies under different temperatures, and it grows best under 1.5 %
      salinity while 37 degrees C. The aim of these researches is to provide an
      evidence for the prevention and cure of TWN3. According to the appearance of the
      diseased Silurus meridionalis Chen and results of artificial infection test on
      crucian carps, it is considered that Silurus meridionalis Chen is infected
      through digestive system and it is also recommended that Bdellovibrio should be
      used in biological control. Although the pathogenicity of P. vulgaris is
      extensive, there has been no report that P. vulgaris is considered as the
      pathogen of cultivated Silurus meridionalis Chen so far. In addition, the
      identification of strain TWN3 has positive effects on the future research on the
      taxonomy of Proteus.

PMID- 17436616
TI  - [The phylogenetic relationship of cultivated isolates of Ganoderma in China
      inferred from nuclear ribosomal DNA ITS sequences].
AB  - Nuclear ribosomal DNA ITS sequences have been used to investigate phylogenetic
      relationships between 34 Ganoderma isolates cultivated in China. Five distinct
      groups were identified: the subgenus Elfvingia, the sect. Phaeonema, and three
      groups within the sect. Ganoderma. Most of the Ganoderma isolates (85.7%) formed
      a single group within the sect. Gantoderma. The result indicated clear genetic
      diversity between the subgenus Elfvingia and the sects Phaeonema and Ganoderma,
      but a smaller degree of genetic diversity between the three groups placed within
      the sect. Ganoderma. Analysis of molecular data is a more effective and useful
      approach for studying the taxonomy of Ganoderma, and for establishing
      phylogenetic relationships within the genus, compared to methods based on
      fruiting body morphology.

PMID- 17436617
TI  - [Cloning and characterization of gerM gene involved in germination in Bacillus
      thuringiensis].
AB  - In Bacilli, gerM is a very conservative gene. Primers were designed according to
      the gerM gene sequence of Bacillus cereus, and a 640bp DNA fragment was obtained
      from Bacillus thuringiensis subsp. kustaki 1. 175 by PCR. Using this fragment as
      a probe, a 4.5kb DNA fragment was cloned from the partial DNA library of Bacillus
      thuringiensis subsp. kustaki 1.175. Sequence analysis showed that the fragment
      contains one complete open reading frame (ORF) that encodes a 349-amino acid (aa)
      protein, which has high homology with GerM protein from Bacillus subtilis. This
      gene was designated gerM (GenBank Accession No. DQ537381 ) . RT-PCR analysis
      showed that gerM gene was only expressed in the process of sporulation,
      suggesting gerM is not required for the vegetative growth. The function of the
      gerM gene was studied by a strategy of gene disruption, and the resulting gerM
      disruption mutant did show normal growth and sporulation. However, gerM
      disruption mutant spores germinate slower than wild-type spores when triggered by
      L-alanine or inosine, indicating that gerM is required for the spore normal
      germination initiated by L-alanine or inosine in Bacillus thuringiensis.

PMID- 17436618
TI  - Some essential elements on the inlC promoter for prfA-dependent regulation in
      Listeria monocytogenes.
AB  - To study some essential elements of a PrfA-dependent promoter of Listeria
      monocytogenes, a series of promoter mutants incorporated into upstream of a
      promoterless lacZ gene were constructed from a known listerial PrfA-dependent
      promoter, inlC promoter, by PCR-mediated site-directed mutagenesis and
      recombinant PCR technique and then electroporated into L. monocytogenes wild-type
      strain P14, prfA * mutant Pl4a and prfA deletion mutant A42. The corresponding
      transcription activities of altered promoters were measured by the beta
      galactosidase assay. The results showed that a PrfA-box-like sequence ("pseudo
      PrfA-box"), TTAACAGCGTTTGTTAA, 22bp downstream of the transcriptional start site
      of PinlC had no ability to enhance or inhibit the PrfA-dependent transcription of
      inlC promoter, even it was modified to the "ideal PrfA-box" TTAACATTTGTTAA.
      However, there was almost no PrfA-dependent transcriptional activity from the
      mutants deletion of the inlC original PrfA-box. Moreover, altered spacing between
      3'-end of the PrfA-box and 5'-end of the -10 box in the inlC promoter region
      affected transcription efficiency dramatically, which also happened in another
      promoter-dependent promoter, plcA promoter. Those above suggested that besides
      the "PrfA-box", additional unknown PrfA-dependent promoter structure(s) or
      sequence(s) might be required for the PrfA binding to the promoter and initiation
      of transcription. Furthermore, the distance between the PrfA-box and the -10 box
      should be fixed to 22 or 23bp for the PrfA-dependent transcription.

PMID- 17436619
TI  - [Construction of plant expression vectors with fusion gene of Helicobacter pylori
      cagA, ureB and ctb and its genetic transformation in tobacco].
AB  - Helicobacter pylori (Hp) is the principal cause of most chronic active gastric
      and peptic ulcer disease, and also is closely related with gastric cancer and
      MALT lymphoma. Current vaccines are expensive to produce and deliver, however,
      transgenic plants expressing recombinant vaccine immunogens offer an attractive
      and potential inexpensive alternative to vaccination and injection. In this
      study, plant expression vectors which harbor Hp related proteins CagA and UreB
      were constructed. Fusion gene ctb-linker-cagA and ctb-linker-ureB were cut from
      vectors p1300-WxCLCN and p1300-WxCLUN, and then constructed into vector
      pCAMBIA2301 which was under the control of the CaMV 35S promoter by series
      molecular methods. Those reconstructed vectors were named p2301-35SCLCN and p2301
      35SCLUN and were introduced into Agrobacterium tumefaciens strain EHA105 .Tobacco
      was transformed by co-cultivating leaf discs with Agrobacterium strains harboring
      fusion genes. The regenerated Kanamycin-resistant transforms were selected,
      elongated, rooted and transferred fdr flowering in greenhouse. Recombinant plant
      expression vectors were confirmed by digestion and PCR and transgenic plants were
      analyzed by PCR, GUS histochemical assays, PCR-Southern blot. The results show
      that more than 80% transgenic plants are confirmed to be positive ones and these
      results also indicate that ctb-linker-cagA and ctb-linker-ureB are integrated
      into the genomic DNA of the tobacco which laid a solid foundation for the
      research of establishing transgenic plants as bioreactors to carry microbe
      antigen and Hp transgenic plant vaccines.

PMID- 17436620
TI  - [Cloning of bldAa and the effect on morphological differentiation and avermectins
      production in Streptomyces avermitilis NRRL8165].
AB  - bldA encodes the only tRNA that efficiently translates the rare UUA leucine codon
      in Streptomyces coelicolor. bldA inactivation leaded to defection in
      morphological development and production of two of four known antibiotics in S.
      coelicolor. A bldA homologue, termed bldA. , has been identified in the sequenced
      genome of Streptomyces avermitilis MA4680. To investigate the function of bldA.,
      genomic DNA of S. avermitilis NRRL8165 was digested with BamH I and the 5 - 6kb
      was fractioned and ligated with the BamH I digested E. coli plasmid vector
      pIJ4642 to yield a sub-library. A clone containing bldAa and its flanking
      sequence was obtained by screening from this genome sub-library. pHL358, a bldA,
      replacement plasmid, was constructed using the lambdaRED mediated PCR-targeting
      technique, and conjugated into S. avermitilis NRRL8165.Three bldA-disruption
      mutant strains (named TW10) were obtained, which showed a bald phenotype,
      indicating that bldA, controlled the morphological differentiation of S.
      avermitilis . HPLC analysis of the TW10 fermentation culture showed that TW10 did
      not synthesize avermectins anymore, suggesting that the synthesis of avermectins
      were dominated by bldAa . There are TTA codons within aveA3 and aveR of the
      avermectin biosynthesis gene cluster, suggesting that the translation of the two
      genes may depend on bldAa, which were consistent with the experimental results.

PMID- 17436621
TI  - [The C4 proteins of Ageratum yellow vein China virus and Stachytarpheta leaf curl
      virus are suppressors of RNA silencing].
AB  - RNA silencing is a highly conserved mechanism in many eukaryotic organisms that
      involves sequence-specific RNA degradation. One of the important roles of RNA
      silencing is antiviral infection. To counter this defense mechanism, many plant
      viruses have evolved or acquired functional proteins (suppressors) for
      suppression of RNA silencing. Geminiviruses are a family of small circular single
      stranded DNA (ssDNA) viruses that cause severe diseases in major crop plants
      worldwide. AC2 (C2) and AC4 (C4) proteins of many geminiviruses were reported to
      be suppressors of RNA silencing. Ageratum yellow vein China virus (AYVCNV) and
      Stachytarpheta leaf curl virus are two distinct geminiviruses identified in
      China. In this study, the functions of C4 of AYVCNV and StaLCV were studied,
      analysis of infectivity of AYVCNV and StaLCV C4 genes using Tobacco rattle virus
      (TRV) vector were carried out in Nicotiana benthamiana plants, N. benthamiana
      plants expressing C4 can induce the virus-like symptoms, indicating that the C4
      gene of AYVCNV or StaLCV is symptom determinant. In experiment of suppression of
      RNA silencing, C4 protein of AYVCNV or StaLCV can suppresses the local silencing
      of gfp in transgenic N. benthamiana plants (16c), suggests that both of them are
      suppressors of RNA silencing. The above results indicate that C4 of

PMID- 17436622
TI  - [Screening and identification of a photosynthetic bacterium reducing selenite to
      red elemental selenium].
AB  - Selenium is essential element for humans and animals but is very toxic at higher
      concentrations. In four inorganic states of selenate [SeO4 2- ( VI)], selenite
      [SeO3 2- (IV)], elemental selenium [Se (0)] and selenide [Se2- (- II )], selenite
      is well known to be more soluble and higher toxic than other three forms. Many
      microorganisms have the capacity to reduce selenite to red elemental selenium,
      which provide the potential to cope with the detoxification of pollution and to
      use the biological availability of red elemental selenium. Strain S3 that was
      more resistant to sodium selenite was selected from 20 photosynthetic bacteria
      preserved in laboratory. The red granule produced by S3 was identified as
      elemental selenium ( Se) by transmission electron microscopy and Electron
      Dispersive X-ray (EDX) analysis. The granule diameter of the red elemental
      selenium was 5nm - 200nm, similar as the Nano-Se that has bioavailability.
      Morphology, physiology and photosynthetic pigments analysis results showed that
      strain S3 was essentially consistent with Rhodobacter azotoformans . The 16S rDNA
      sequence analysis (GenBank accession number DQ402051) suggested that strain S3
      was clustered together with R. azotoformans in phylogenetic tree, with the
      sequence identity of 99% . Based on all the results of taxonomy, strain S3 was
      identified as R. azotoformans S3. The effects of selenite on growth kinetics and
      the ability to resistant selenite of strain S3 were investigated. In contrast to
      Rhodospirillum rubrum which was reported not to reduce selenite until the end of
      exponential growth, strain S3 transformed selenite (1.25mmol/L) at the beginning
      of the growth, suggesting that strain S3 and Rs. rubrum may employ different
      strategies to reduce selenite. Strain S3 can grow in the presence of up to
      125mmol/L sodium selenite, which is much higher than those which could be
      resisted to by other bacteria such as Escherichia coli ( < 20mmol/L) and
      Ralstonia metallidurans CH34 ( < 6mmol/L) . It is firstly reported that R.
      azotoformans has the capacity to reduce selenite to red elemental selenium.

PMID- 17436623
TI  - [Cloning, sequence analysis and expression of anthranilate synthetase gene in
      Corynebacterium pekinense].
AB  - Anthranilate synthetase (EC4.1.3.27;AS) genes from wild-type Corynebacterium
      pekinense AS1.299 and its mutant PD-67 were cloned and sequenced. Analysis of PCR
      fragments revealed that three ORFs existed, which corresponded to trpL, trpE and
      trpG gene, respectively. Six bases changes that resulted in the changes of five
      amino acids were found in the trpE structural gene of C. pekinense PD-67 and a
      single-base change that resulted in an amino acid substitution was found in the
      trpG structural gene of C. pekinense PD-67.A homology comparison revealed that C.
      pekinense AS1.299 was closely related to Corynebacterim glutamicum ATCC 13032 and
      Brevibacterium lactofermentum. An internal promoter was found in the upstream of
      the trpL gene from C. pekinense and it functioned in E. coli, but a single-base
      exchange (A to G) existed in the-35 box of PD-67. The trpEG genes from the wild
      type strain and its mutant were expressed both in C. pekinense AS1.299 and PD-67,
      and the specific enzyme activities of transformed C. pekinense were much higher
      than that of the parental strains. The amplification of the activity of AS
      yielded 22.39% increase of L-tryptophan production, but the cell growth became
      slower than PD-67.

PMID- 17436624
TI  - [Cloning and heterologous expression of the gene of laccase C from Trametes sp.
      420 and potential of recombinant laccase in dye decolorization].
AB  - A new laccase gene (lacC) was cloned from the genomic DNA isolated from Trametes
      sp. 420, a new laccase-producing fungus, using the degenerate primers based on
      the conserved copper-binding regions in fungal laccases. Long distance-inverse
      PCR (LD-IPCR) was used to amplify the flanking sequences of the gene. The lacC
      DNA sequence obtained was 3640 base pairs (bp), including the entire open reading
      frame (2263bp) and the 5'-and 3'-noncoding regions. The lacC cDNA sequence is
      1560bp, encoding a 519 amino acid protein. The deduced peptide sequence of LacC
      contains ten putative N-glycosylation sites and four conserved copper-binding
      regions. The lacC cDNA without its signal sequence was cloned into the expression
      vector pPIC9K through the pPIC9 plasmid and transformed into the Pichia pastoris
      strain GS115.The positive transformant was cultured at 20 degrees C in BMM medium
      containing 0.3mmol/L CuSO4 and 0.8% alanine, with the yield of the recombinant
      laccase rLacC being 1.62 x 10(4) U/L after a 9-day cell growth. Furthermore, the
      crude enzyme was used to decolorize several synthetic dyes at a final
      concentration of 50mg/L. The results showed that rLacC (6U/L) possessed the
      valuable ability to decolorize dyes of triarylmethane and azo types tested. The
      presence of low molecular weight redox mediators of ABTS and HBT increased the
      efficiency and velocity of dye decolorization significantly.

PMID- 17436625
TI  - [Cloning and expression of a delta6-fatty acid desaturase gene from Rhizopus
      stolonifer in Saccharomyces cervisiae].
AB  - Fatty acid composition of fungi is analysed through the gas chromatography( GC)
      technique. With specific activity a novel enzyme delta6-fatty acid desaturase was
      screened and isolated from Rhizopus stolonifer. In this study R. stolonifer was
      identified as a fungal species that produced plentiful gamma-linolenic acid. A
      1475bp full-length cDNA, designated as RnD6D here, with high homology to fungal
      delta6-fatty acid desaturase genes was isolated from R. stolonifer using reverse
      transcription polymerase chain reaction and rapid amplification of cDNA ends
      methods. Sequence analysis indicated that this cDNA sequence had an open reading
      frame of 1380bp encoding a deduced polypeptide of 459 amino acids. Bioinformatics
      analysis characterized the putative RnD6D protein as a typical membrane-bound
      desaturase, including three conserved histidine-rich motifs, hydropathy profile
      and a cytochrome b5-like domain in the N-terminus. To elucidate the function of
      this novel putative desaturase, the coding sequence was expressed in
      Saccharomyces cerevisiae strain INVScl. A novel peak corresponding to gamma
      linolenic acid(GLA) methyl ester standards was detected with the same retention
      time, which was absent in the cell transformed with empty vector. The percentage
      of this new GLA was 12.25% of total fatty acids. The result demonstrated that the
      coding produced delta6-fatty acid desaturase activity of RnD6D which led to the
      accumulation of gamma-linolenic acid.

PMID- 17436626
TI  - [Expression and characterization of formate dehydrogenase gene in Klebisella
      pneumoniae].
AB  - Glycerol can be converted to 1,3-propanediol by the anaerobic fermentation of
      Klebsiella pneumoniae, during which reducing equivalent NADH was consumed.
      Therefore, the availability of NADH would be critical for the yield of 1, 3
      propanediol. In this paper, formate/formate dehydrogenase system was used for the
      regeneration of in vivo NADH and the improvement of 1, 3-propanediol production.
      Formate Dehydrogenase gene (fdh) was amplified from Candida boidinii genome by
      PCR and the purified PCR product was inserted into the vector pMD18-T Simple to
      construct plasmid pMD18-T Simple-fdh, which was transformed into Escherichia coli
      DH5alpha and recombinants were selected by blue-white selection. From the
      transformant the fdh gene was separated and inserted into pMALTM-p2X to construct
      expression vector pMAL-p2X-fdh, which was transformed into Klebsiella pneumoniae
      YMU2 and a recombinant strain Klebsiella pneumoniae F-l was obtained. The plasmid
      stability of strain F-l and the conditions of fdh expression induced by IPTG were
      studied. It was demonstrated that the plasmid had good stability, and 0.5mmol/L
      IPTG would induce the expression of protein encoded by fdh gene with the
      molecular weight of 40.2kDa. The enzyme activity reached 5.47U/mg crude protein
      when K. pneumoniae F-I was induced for 4h by 0.5mmol/L IPTG. Compared with that
      of the parent strain K. pneumoniae YMU2, the yield of 1,3-propanediol of
      recombinant strain F-1 increased by 12.5% in the anaeribic bioreactor.

PMID- 17436627
TI  - [Analysis of cellulase synthesis mechanism in Trichoderma reesei using red
      fluorescent protein].
AB  - Comprehensive analysis of the mechanism of metabolite synthesis in filamentous
      fungi is important for optimization of the filamentous fungus related industrial
      fermentation processes. In this work, the mechanism of cellulase synthesis in
      Trichoderma reesei was analyzed with red fluorescent protein (DsRed) as the
      reporting protein. The expression cassette for heterologous protein expression in
      T. reesei was constructed, through which the DsRed gene was inserted into the
      chromosomal DNA of T. reesei. The recombinant T. reesei strain, in which
      expression of DsRed was controlled by the promoter of cellobiohydrolase gene, was
      designated as T. reesei TR2. Expression of DsRed in T. reesei TR2 under different
      culture conditions was analyzed by using a fluorescent microscopy, and thereby
      the mechanism of cellulase gene expression in T. reesei could be interpreted.
      With induction of lactose, the pattern of change of red fluorescence in T. reesei
      TR2 was similar to that of the cellulase activity in the cultivation supernatant.
      As the culture aged, the red fluorescence in the mycelial increased. This was
      followed by a reduction in the end of the culture period because of death and
      autolysis of the mycelial. In the spatial aspect, the red fluorescence was
      distributed uniformly in the whole hypha after induction, indicating that all the
      three morphology including apical compartment, subapical compartment and hyphal
      compartment played a same role in cellulase synthesis. When T. reesei TR2 was
      cultivated without induction, faint red fluorescence appeared after a relative
      long period of cultivation, indicating that a small amount of cellulase was still
      synthesized without induction. This result was useful in explaining the mechanism
      of cellulase induction by insoluble cellulose.

PMID- 17436628
TI  - [Synthesis of hybrid antimicrobial peptide CecA-mag gene and it's secretion
      expression in Pichia pastoris].
AB  - According to the partiality codon of Pichia pastoris, hybrid antimicrobial
      peptide CecA-mag gene was synthesized and cloned into pPICZa-A to construct the
      recombinant expression vector pPICZa-A-CA. The SacI-linearized plasmid pPICZalpha
      A-CA was transformed into P. pastoris SMD1168 by electroporation. Under the
      control of the promoter AOX'(alcoholoxidase') , an approximately 1.9kDa cecA-mag
      protein was expressed. Antibacterial assays demonstrated that cecA-mag had broad
      spectrum of antimicrobial property against Gram-positive as well as Gram-negative
      bacteria especially showed potent antibacterial activity against ampicillin
      resistant bacteria, such as pathogenic E. coli. In addition, the hybrid
      antibacterial peptide showed an extreme heat stable and acid stable
      characteristic. These results suggest that the P. pastoris expression system can
      be used to produce large quantities of fully functional cecA-mag for both
      research and industrial purpose. Based on these characteristics, the recombinant
      antibacterial peptide cecA-mag displays application foreground in the field of
      prevention of disease, and can be used as additives of animal feedstuff and so
      on.

PMID- 17436629
TI  - [Expression of functional human STK11 protein in Escherichia coli].
AB  - STK11 (serine/threonine kinase 11 ), a multi-functional protein reported
      recently, possibly participates in a broad range of cellular processes, including
      regulation of cell cycle, p53-mediated apoptosis, ras-induced cell transformation
      and cell polarization. An efficient expression of functional STK11 in Escherichia
      coli will promote the study on its structure and function. Inducible prokaryotic
      expression vector pET-Nus-STK11 (with Nus fusion tag) was constructed with pET
      44a( + ) and the cDNA of STK11 gene cloned in our lab. pET-Nus-STK11 was then
      expressed in both BL21 (DE3) and Rosetta-gami (DE3)pLysS on the induction of
      IPTG. SDS-PAGE and Western blot indicated that recombinant Nus-STK11 obtained in
      BL21(DE3) was in the form of inclusion body, whereas that from Rosetta-gami
      (DE3)pLysS was mainly in soluble fraction, and accounted for 8.9% and 16.7% of
      the total protein, respectively. After purification and refolding, the obtained
      recombinant protein was carried into SMMC-7721 cells by Chariot to observe its
      influence on cell growth and cell cycle. Nus-STK 1 from BL21(DE3) was proved to
      be lack of any tumor-suppression activity, while a growth inhibitory ratio of
      47.05% on SMMC-7721 cell was observed, and cell cycle progression of SMMC-7721
      cells was also arrested from G0/G1 to S phase, with the Nus-STK11 from Rosetta
      gami (DE3) pLysS, indicating that the above recombinant fusion protein from
      Rosetta-gami (DE3)pLysS had significant biological activity. This is the first
      report on functional recombinant STK11 protein expressed in Escherichia coli.

PMID- 17436630
TI  - [A novel metabolism pathway for the biodegradation of chloroanilines].
AB  - Up to date, p-chloroaniline was reported to be biodegraded only through ortho-or
      modified ortho-cleavage pathway. In this paper, the intermediates of p
      chloroaniline metabolized by strain Diaphorobacter PCA039 were analyzed and
      identified by HPLC and LC/MS methods. The results showed that intermediates such
      as 4-chlorocatechol, 2-hydroxy-5-chloromuconic semialdehyde, 5-chloro-4
      oxalocrotonate, 5-chloro-2-oxo-4-hydroxypentanote, chloro-acetate were formed and
      consumed in order during the degradation of p-chloroaniline by strain
      Diaphorobacter PCA039.These compounds are the intermediates of a typical meta
      cleavage pathway. In addition, strain Diaphorobacter PCA039 could produce the
      induced catechol 2, 3-dioxygenase when it grows on p-chloroaniline as sole
      carbon, nitrogen and energy sources, and use the intermediates of the meta
      cleavage pathway such as catechol, 4-chlorocatechol, 2-hydroxy-5-chloromuconic
      semialdehyde as sole carbon and energy sources. Combining its physiological and
      biochemical properties and the results of LC/MS analysis, it was concluded that
      strain Diaphorobacter PCA039 could also degrade p-chloroaniline through meta
      cleavage pathway as Fig. 4, which is a new pathway for the biodegradation of p
      chloroaniline. It is significant to the study of biodegradation, metabolic
      mechanism, properties of the enzymes and the expression and regulation of the
      genes involved in the degradation of p-chloroaniline.

PMID- 17436631
TI  - [The plasmid harboring cry26Aa may contribute to the phenomenon of spore-crystal
      connection in Bacillus thuringiensis subsp. finitimus].
AB  - Parasporal crystal in B. thuringiensis subsp. finitimus T02 forms inside the
      exosporium and remains attached to the spore after mother cell lysis. Two crystal
      protein gene cry26Aa and cry28Aa were cloned from this strain. The relationship
      between the phenomenon of spore-crystal connection and the plasmids was
      investigated in this work. Mutants BMB1151 curing of the plasmid harboring
      cry26Aa, and BMB1152 curing of all plasmids were obtained from B. thuringiensis
      subsp. finitimus T02.The spore-crystal connection didn't appeared when cry26Aa
      and cry28Aa were transformed back into the strain BMB1152 by shuffle vector alone
      or in combination together. It suggested the plasmids of B. thuringiensis subsp.
      finitimus TD2 may contribute to the phenomenon. When gene cry26Aa was transformed
      back into in the strain BMB1151, spore-crystal connection didn't form either. So
      the plasmid harboring cry26Aa may also contribute to the phenomenon of spore
      crystal connection in B. thuringiensis subsp. finitimus T02.

PMID- 17436632
TI  - [Biology of two lysogenic phages from Bacillus thuringiensis MZ1].
AB  - A Bacillus thuringiensis (Bt) fermentative strain MZ1 (subsp. kurstaki) , from a
      company in Meixian County of Guangdong Province, produce toxins during
      sporulation and are extensively used in the field to control pest insects
      (Lepidoptera) in China. But some unknown or random factors that inhibited or
      stopped B. t growth in the fermentation can be regarded as reflecting the exist
      of lysogenic phage. Therefore, strain MZI and its lysogenic phages were studied
      in this paper. With indicator strain ZK1, two kind of phage plaques, one with
      about 3mm diameter and the other with about 1mm diameter, can be observed after
      strain MZ1 cultured in plates or flasks was induced by mitomycin C. Then, two
      lysogenic phages, namely MZTP01 and MZTP02, were isolated and characterized in
      biology. They belonged to family Siphoviridae, which had icosahedral heads
      (MZTP01 :82nm x 85nm; MZTP02: 75nm x 55nm) and long tails (MZTP01: 220nm x 18nm;
      MZTP02: 183nm x 12nm) without flexibility. Host range examination showed that six
      and seven (including indicator strain ZKl) out of 113 B. t strains saved in our
      laboratory were sensitive to MZTP01 and MZTP02, respectively. MZTP01 was more
      stable than MZTP02 against pH value, ultraviolet and heat treatment, but contrary
      against organic solvents. For MZTP01 and MZTP02, K values in the neutralization
      reactions were 45 and 326, respectively. Both phages had no relationship in their
      antigenicity. Burst size of phage MZTP02 was 175, two times more than that of
      MZTP01. Latent time of MZTP02 was 40min, one times shorter than that of MZTP01.
      It was suggested that both phages DNA be linear dsDNA through the typical
      absorption curves, reaction with diphenylamine, DNase sensitivity and acridine
      orange staining. And this was in good accord with the previous findings that all
      tailed phages being dsDNA moleculars. The genomic DNA and their restriction maps
      showed that both molecular weights should be between 9.4 - 23kb. Both phage
      genomic DNAs were digested by Hind III, producing eight and nine bands,
      respectively. The results above show that strain MZl is proved a double lysogen.
      It is considered to be the main reason of great losses in the production. The
      biological information of the two lysogenic phages belonging to strain MZ1 is
      provided to help solve the problem and the two lysogenic phages is prepared for
      complete DNA sequencing in the next step.

PMID- 17436633
TI  - [Analysis of bacterial communities in vegetable and straw wastes composting by
      Biolog method].
AB  - Bacterial communities were analyzed using Biolog method in agricultural waste
      composting. The results of cluster analysis and principle component analysis
      indicated that bacterial communities varied greatly during the first stage of
      composting, while began to stabilize during the second stage. Bacteria that could
      utilize the first and second kinds of carbon sources on Biolog plate were found
      to be the dominant ones during composting, which were also believed to be related
      with lignocellulose degradation. Thermophilic bacteria were believed to be able
      to metabolize the fourth and sixth kinds of carbon sources on Biolog plate.
      Thereinto, the fourth kinds of carbon sources were also connected with
      lignocellulose transformation. The bacteria utilizing the sixth kinds of carbon
      sources were just able to metabolize some simpler organic matters.

PMID- 17436634
TI  - [Study on the structure and function of a stable methane-oxidizing mixed
      microbial consortium].
AB  - From an agricultural sample taken in Chongqing, a stable methane-oxidizing mixed
      microbial consortium was established by enrichment culture with methane as a sole
      source of carbon and energy. The mixed consortium showed high capability of
      phenol degradation and 1,2-epoxypropane production from propene. More than 99% of
      phenol at an initial concentration of 600mg/L could be degraded by the mixed
      microbial consortium after 11 h of cultivation. The productivity of 1, 2
      epoxypropane could be increased with the decrease of phosphate concentration. The
      concentration of 1, 2-epoxypropane produced could reach to 5.0mmol/L. The
      bacterial structure of the methane-oxidizing mixed microbial consortium was
      analyzed by pure culture isolation combining with 16S rRNA and PCR of the related
      MMO functional genes. The results showed that the methane-oxidizing mixed
      microbial consortium was composed of a type 1U methanotroph identified as
      Methylosinus trichosporium and at least 4 kinds of heterotrophs ( Comamonas
      testosteroni, Cupriavidus metallidurans, Acinetobacter junii and Stenotrophomonas
      maltophilia ). M. trichosporium Y9, isolated from the mixed consortium, harbored
      both sMMO and pMMO genes.

PMID- 17436635
TI  - [Bioactivity survey of natural microbial consortium from mangrove].
AB  - Microbial natural products have been mainly acquired by pure culture. While in
      nature, different microorganisms in one habitat may work together as a whole to
      produce special secondary metabolites to adapt to their environments. "Quorum
      sensing" is a way that they would use. A microbial consortium is like a multi
      cellular individual that different microorganisms interact with each other to
      fulfill a special function. A marine fungus only produce antibiotics when a
      bacterium co-cultured (Cueto et al, 2001); and some traditional Chinese
      fermentation food are produced by mixed culture. These inspired us that directly
      using natural microbial consortium instead of isolate the individual
      microorganism may be a worth to risk in search for bioactive products. In this
      research, One hundred and eighty one samples were collected from three mangrove
      areas of Hainan, Guangxi and Guangdong, in China, which were fermented directly
      and evaluated for their anti-bacteria, anti-fungi and anti-cancer cell
      activities. Fifteen samples with high activities were further studied.
      Microorganisms were isolated from these 15 high bioactive samples and re-detected
      for their bioactivity, among which, microorganisms isolated from 5 samples that
      numbered 1106, 1122, 1116, 1214 and 1305 didn' t show any activity although the
      un-isolated samples themselves showed high bioactivity. Four strains were
      isolated from one sample of number 1146. Among these strains, one strain showed
      the same bioactivity targets as the sample itself , but lower activity of anti
      fungi than the sample itself. The other three strains didn't show any
      bioactivity. Microorganisms isolated from three samples that numbered 1161, 1123
      and 1111, changed their initial bioactivity targets. These results suggested that
      natural microbial consortium culture have the potential to produce bioactive
      metabolites. It is supposed that some uncultured microorganisms or the community
      action may be the reason for their activity. This is an initial step on using
      microbial consortium to produce bioactive metabolites.

PMID- 17436636
TI  - [Cloning, expression and characterization of a new hybrid AMP gene of Hex-Mag].
AB  - To enhance the antibacterial ability of Magaininl-12, its N side was joined with
      an alkaline peptide named Hexapeptide( RRWQWR), which would make Magaininl-12
      cling to the membrane of bacterial cells even tighter. According to the
      partiality codon of Pichia pastoris, a new hybrid antibacterial peptide Hex-Mag
      was designed based on the sequence of Hexapeptide and Magainin( 1-12).
      Synthesized through gene splicing by overlap extension, the hybrid gene was
      cloned into pPIC9 to construct the expression vector pPIC9-HM. After restriction
      enzyme analysis and purification, the pPIC9-HM was transformed into Pichia
      pastoris GS115. And the positive clones screened by the phenotype were induced by
      methanol. After optimized the requirements for the flask-shaking culture
      fermentation, the hybrid antibacterial peptide was expressed on high level. The
      new peptide, which has a weight of 2.3kDa, could remain its inhibition activity
      after treating for more than 3 hours in boiled water. Detected by agrose
      diffusion assay, Hex-Mag showed its broad-spectrum antibacterial abilities not
      only to Gram-negative bacteria but also to Gram-positive bacteria. The function
      of additive positive charges were testified by the antibacterial experiments, and
      the results showed the activity of Hex-Mag was stronger than that of Magainin1-12
      obviously.

PMID- 17436637
TI  - [Expression and immunogenic analysis for the tandem-arranged multiple mimic
      epitope gene of infectious bursal disease virus].
AB  - Five mimic epitopes of Infectious bursal disease virus (IBDV) have been
      identified from a 12-mer phage-displayed peptide library by 5 monoclonal
      antibodies. Based on the sequences of the five epitopes, multiple epitope gene
      5epis was constructed by the five epitopes being tandemly arranged and linked
      with 4-peptide GGGS. The expression plasmid pET-5epis was constructed and
      successfully expressed in E. coli. The resultant protein of 5epis was called
      r5EPIS. The results from SDS-PAGE analysis showed that the proportion of r5EPIS
      was 15% of the total bacterial proteins and the molecular weight of r5EPIS was
      10kDa. By use of parallel immunoblotting test with corresponding monoclonal and
      polyclonal antibodies, the immunological specificity and reactivity of r5EPIS
      against IBDV have been verified. Rabbits were subcutaneously injected with r5EPIS
      (400 micro g per injection), twice with 7 days interval. The titers of the IBDV
      specific antibody measured by indirect ELISA were up to 1:4000 at the 7th day
      after first immunization and 1:256000 at the 14th day after the second
      immunization. To determine the protective ability of r5EPIS to the challenge of
      IBDV, chickens were injected intramuscularly with r5EPIS in adjuvant twice with 7
      days interval (501g per injection) and the resultant antibody titer was up to
      1:12800 at the 7'h day after the second immunonization. After challenge with
      200ELD50 of virulent IBDV GX8/99 strain, all the chicken in r5EPIS-immunized
      group were survived in contrast to the mortality of 86.7%(13/15) in adjuvant
      control group, suggesting that r5EPIS had a potent ability to generate protective
      immune response and it implied that the constructed gene 5epis is a prospective
      candidate for the development of epitope-based IBD vaccine.

PMID- 17436638
TI  - [Prokaryotice expression of the NS1 gene of PPV and renaturation of the
      recombinant protein].
AB  - The antigen of NS1 gene of PPV was amplified by PCR, and the amplified fragments
      were cloned into the prokaryotic expression vector pGEX-4T-1. The insert
      position, the size and the frame were identified by PCR, restriction enzyme
      digestion and the sequence analysis of the recombinant plasmids. The sequence
      analysis results of pGEX-NS1-HN1 showed that the prokaryotic expression vector
      was successfully constructed. The target gene was successfully expressed in the
      host cell BL21 when induced with IPTG. The expression was optimized with proper
      inducing conditions of 1.0mmol/L IPTG, 10 hours and 37 degree C induction. The
      expression of the target protein added up to 29.8% of the total bacterial
      protein. The results of SDS-PAGE indicated that molecular weight of the expressed
      protein was about 52kDa and the expressed protein mainly existed in the inclusion
      body. Western blot analysis proved the recombinant protein has good reactive
      ability against PPV positive serum. The pGEX-NS1-HN1 inclusion body was dissolved
      with 8mol/L urea. Then the expressed protein was renatured by dilution method and
      the systems of GSH and GSSG. ELISA detection proved the renaturation protein has
      good biological activity.

PMID- 17436639
TI  - [Immunogenicity of S1 gene DNA vaccine of mouse hepatitis virus delivered by
      attenuated Salmonella typhimurium].
AB  - The complete S1 gene from mouse hepatitis virus (MHV) was amplified by RT-PCR and
      cloned into the pMD18-T vector. After confirmed by the restriction endonuclease
      analysis and PCR amplification, the positive clone of S1 gene was sequenced and
      then was transferred into eukaryotic expressing vector pVAXI. The recombinant
      plasmid pVAX1-S1 was transfected into COS-7 cells. The expressed S1 protein was
      successfully detected with indirect immunofluorescent assay. Finally, The
      recombinant plasmid pVAX1-S1 was transformed by electroporation into attenuated
      Salmonella typhimurium strain SL7207 and confirmed by PCR and Salmonella
      agglutination test. The recombinant was named as SL7207(pVAX1-S1). 6-week-old
      BALB/c mice were inoculated orally with SL7207 (pVAX1-S1) at dosage of 5 x 10 (8)
      CFU, 1 x 10(9) CFU and 2 x 10(9) CFU respectively. The immunized mice showed no
      clinic symptom. The results suggested that SL7207 (pVAX1-S1) was safe for mice
      after oral immunization at dosage of 2 x 10(9) CFU or below. BALB/c mice were
      immunized orally with SL7207 harboring recombinant plasmid at the dosage of 109
      and boosted two weeks later with the same dose, for a total of three times. The
      recombinant Salmonella SL7207 ( pVAX1-S1 ) could induce significant humoral
      immune response in mice compared with the control (P < 0.05 or 0.01) at 2 w post
      boosting and 2 w post-three immunization. The antibodies against MHV were also
      detected in small intestinal mucosal samples from immunized mice at 2 w post
      three immunization. These results indicated that recombinant SL7207(pVAX1-S1)
      induced both systemic and local mucosal immunity.

PMID- 17436640
TI  - [Real time PCR quantification of ammonia-oxidizing bacteria in aerobic granular
      sludge and activated sludge influenced by pentachlorophenol].
AB  - The V2 region of the 16S ribosomal DNA of the ammonia-oxidizing bacteria (AOB)
      was amplified directly from the environmental sample by using the specific PCR
      primers. The purified PCR product was cloned into T-vector and was identified as
      16S rDNA fragment of AOB by sequencing and Real-time PCR method. Then, the
      recombined plasmid was used as standard molecule sample in Real-time PCR for AOB
      quantification. The numbers of the AOB were monitored in samples of both aerobic
      granular sludge and activated sludge influenced by PCP by using Real-time PCR.
      The results showed that the numbers of AOB in aerobic granular sludge and
      activated sludge were 4.28 x 10(7) 5.44 x 10(6) cells/g dried sludge and 2.51 x
      10(9) +/- 8.61 x 10(8) cells/g dried sludge without PCP in the reactors,
      respectively. With the increase of PCP concentration (from 0mg/L to 50mg/L), the
      numbers of AOB in both types of sludge had no obvious change( P > 0.05) . The
      numbers of AOB had no obvious correlation with ammonia removal ( P > 0.05) . The
      main effect of PCP on AOB in both types of sludge was to inhibit their metabolic
      activity.

PMID- 17436641
TI  - [Construction of recombinant retroviral vector carrying porcine interferon-gamma
      and its expression in porcine kidney cells (PK-15)].
AB  - Porcine interferon-gamma (PoIFN-gamma) of Chinese local brand, Meishan porcine,
      was cloned and inserted into retroviral vector pLXSN (neo r) . Using
      Lipofectamine, this recombinant plasmid was transfected into retroviral packing
      cell line, PA317 cells. These transfected cells were selected by DMEM containing
      400microg/mL G418 for one week. RNA was extracted from the supernatant of these
      selected PA317 cells and the PoIFN-gamma gene could be amplified by RT-PCR.
      Pocine kidney cells and PK-15 cells were infected by the supernatant and were
      selected by 400 microg/mL, 600 microg/mL and 800 microg/mL G418, respectively.
      Those PK-15 cells were detected by indirect immunofluorescence assay and it was
      found that PoIFN-gamma mainly anchored in cellular membrane. The supernatant of
      the selected PK-15 was tested for the antiviral bioactivity after 48 hours of
      passage. The anti-VSV (vesicular stomatitis virus) activity in MDBK (bovine
      kidney cell) was 1200IU/10(6) cells. In addition, the effect of rPoIFNgamma-anti
      FMDV was determined using cytopathic effect inhibition. The results indicate that
      PoIFN-gamma has been inserted into retroviral vector and recombinant retrovirus
      has been successfully packaged in PA317 cells. Furthermore, this retrovirus can
      infect PK-15 cells and express PoIFN-gamma with natural antiviral bioactivity and
      can inhibit VSV and FMDV.

PMID- 17436642
TI  - [Characterization of Ralstonia solanacearum in different growth phases by high
      performance ion exchange liquid chromatography analysis].
AB  - High performance ion exchange liquid chromatography and laser light scattering
      instrument were employed to characterize Ralstonia solanacearum in different
      growth phases. The pure culture of Ralstonia solanacearum was successfully
      separated into three characteristic fractions. Chromatographic behaviors of
      Ralstonia solanacearum in lag phase, logarithmic phase and stationary phase were
      carefully investigated, and their relationships to the cell concentration, pH of
      fermentation broth and extracellular polysaccharide (EPS I ) content of cell
      surface were analyzed. It was found that the majority of Ralstonia solanacearum
      cells obtained at 8h culture time could not be absorbed to the resin due to the
      strong motility of the cells which could apparently overcome the electrostatic
      interaction. Furthermore, when the mobility of the cells was destroyed by 4%
      formaldehyde treatment, the prolonged retention time was recorded due to the
      stronger adsorbility to the resin. On the other hand, the EPS I content of cell
      surface was determined to increase with the culture time, indicating an
      increasing interaction between the cells and the resin. EPS I content of three
      characteristic chromatographic fractions was determined, and it was found that
      the higher EPS I content led to the longer retention time of the fraction, which
      confirmed the above-mentioned observation. As a result, it is concluded that the
      formation of three chromatographic fractions of the pure culture of Ralstonia
      solanacearum is attributed to bacterial motility and the interaction of EPS I of
      cell surface with the anionic exchange resin, and the novel method of ion
      exchange chromatography of the intact bacterial cells can be a useful tool in
      bacteriological study.

PMID- 17436643
TI  - [Sequence analysis of 16S rDNA and genes of soluble methane monooxygenase from
      Methylomonas sp. GYJ3].
AB  - Soluble methane monooxygenase (MMO) from methanotrophs is a member of binuclear
      iron-containing multicomponent oxygenases, which can catalyze bioconversion of
      methane to methanol at ambient temperature and regulate methane recycle in
      nature. The research focused mainly on the sequence analysis of 16S rDNA and sMMO
      genes from Methylomonas sp. GYJ3. With the aid of the information from GenBank,
      the PCR primers and the sequence primers were designed, obtained a 5690bp of sMMO
      fragment and a 1280bp of 16S rDNA. Sequence comparison for MMOX with counterpart
      of other five strains showed that from 78% to 99% identity in protein level and
      from 71 % to 97% identity in gene level, in the separate comparison of six
      components, only orfY component had a lower identical. The multiple alignment of
      MMOX amino acid sequence with other four strains showed that there is a high
      conservation, especially in two Fe binding regions. 16S rDNA phylogenetic
      analysis demonstrated that Methylomonas sp. GYJ3 is relative with gamma
      proteobacteria. Phylogenetic analysis of MMOX amino acid sequence showed that
      Methylomonas sp. GYJ3 is closer to Methylomonas sp. KSW III of type I
      methanotrophs. It was concluded that Methylomonas sp. GYJ3 is belong to the genus
      of type I methanotroph Methylomonas, and the result was a direct evidence for the
      sMMO can be expressed in type I methanotrophs. The theoretical pI of hydroxylase
      was 6.28 and the theoretical MW of hydroxylase was 248874.41Da.

PMID- 17436644
TI  - [Purification and characterization of a novel alpha-galactosidase from
      penicillium sp. F63 CGMCC1669].
AB  - An a-galactosidase-producing fungus was screened out of 26 filamentous fungi
      isolated from soil by us. Phylogenetic analysis based on the alignment of 18S
      rDNA sequences, combined with the morphological identification, indicated that
      the strain F63 was a member of the genus Penicillium. The a-galactosidase from
      Penicillium sp. F63 was purified to apparent homogeneity by ammonium sulfate
      precipitation, ion-exchange and gel filtration chromatography. The molecular size
      of the purified enzyme is approximately 82kDa estimated by SDS-PAGE. The a
      galactosidase has an optimum pH of 5.0 and an optimum temperature of 45 degrees
      C. The enzyme is stable between pH5.0 and 6.0 below 40 degrees C. The a
      galactosidase activity is slightly inhibited by Ag+ , which is dissimilar to
      other a-galactosidases. Kinetic studies of the a-galactosidase showed that the Km
      and the Vmax for pNPG are 1.4mmol/L and 1.556mmol/L. min(-1) x mg- 1,
      respectively. The enzyme is able to degrade natural substrates such as melibiose,
      raffinose and stachyose but not galactose-containing polysaccharides. The alpha
      galactosidase was identified by MALDI-TOF-MS and its inner peptides were
      sequenced by ESI-MS/MS. The results show that the a-galactosidase is a novel one.

PMID- 17436645
TI  - [Purification and characterization of extracellular halophilic protease from
      haloarchaea Natrinema sp. R6-5].
AB  - A halophilic extracellular protease from a halophilic archaea Natrinema sp. R6-5
      was purified to SDS-PAGE homogeneity using bacitracin-Sepharose 4B
      chromatography. A molecular mass of the purified protease subunit was 62KD
      determined by SDS-PAGE. The protease activity was inhibited by
      phenylmethylsulfonyl fluoride (PMSF), suggesting that the protease belong to
      serine protease. The protease exhibited optimum NaCl concentration is 3 mol/L. At
      the 3 mol/L NaCl concentration, the optimum temperature and the optimum pH were
      45 degrees C and 8.0. The protease could keep high activity and stability in high
      salt environment and had potential application value.

PMID- 17436646
TI  - [A comparison between the effects on DNA-protein cross-links of Saccharomyces and
      E. coli induced by formaldehyde].
AB  - To explore the effect of formaldehyde on DNA-protein cross-links (DPC) in
      eucaryotic cells and prokaryotic cells, Pichia pastoris and E. coli DH5alpha were
      chosen as materials to evaluate the amount of DPC induced by liquid formaldehyde
      in vivo by the method of KCl-SDS assay. The results showed that formaldehyde
      could not induce DPC at low dose(25micromol/L,P > 0.05), but could obviously
      induce DPC at higher dose (125 and 625micromol/L, P < 0.05). The DPC coefficient
      in Pichia pastoris was 10-fold higher than that in E. coli DH5alpha. It is
      concluded that formaldehyde could induce DPC in eucaryotic cells and prokaryotic
      cells with a dose-dependent manner and the DPC coefficient in Pichia pastoris is
      higher than that in E. coli DH5alpha.

PMID- 17436647
TI  - [Bacterial ribulose monophosphate pathway and formaldehyde assimilation].
AB  - Ribulose monophosphate pathway (RuMP), which was originally found in
      methylotrophic bacteria, is now recognized as a metabolic pathway widespread in
      most bacteria and involved in formaldehyde assimilation and detoxification. 3
      Hexulose-6-phosphate synthase (HPS) and 6-phospho-3-hexuloisomerase (PHI) are the
      key enzymes of this pathway. This review describes the physiological significance
      of RuMP pathway derived from a variety of bacteria, the organizations and
      expressional regulations of HPS and PHI genes and the perspectives for
      applications of the two genes.

PMID- 17436648
TI  - [Recenct progress in electricigens and microbial fuel cell].
AB  - The discovery of Electricigens substantially changed the meaning of Microbial
      Fuel Cell (MFC) and exhibited a broad prospect for application. This kind
      microorganism can completely oxidize organic compounds with electrode as sole
      electron acceptor and then transfer the electrons derived from that oxidation
      onto the anode of a MFC through electron transport chain. When the electrons
      transfer from anode to cathode, the current was generated continuously. At same
      time, they gain energy to support their growth from the electron transport. The
      biochemical metabolism process was considered as a new type microbiological
      respiration. Based on the new concept, MFC offered the possibility of efficient
      treatment waste-water and generation electricity simultaneously, which would fuel
      the waste-water into a profitable industry in the future. So the application of
      MFC in the waste-water treatment would be most promising.

PMID- 17436649
TI  - [Overview and analysis of general projects in microbiology funded by NSFC during
      2000 - 2006].
AB  - The general projects on subdisciplines of Microbiology which were funded by the
      National Natural Science Foundation of China (NSFC) during the financial years of
      2000 to 2006 are reviewed in this article. The number of general projects and
      funds involved are analyzed to give an overview of fundamental research in
      microbiology in China. Some important research fields in microbiology that the
      NSFC should support in the future are also recommended.

PMID- 17436650
TI  - [Future airway management challenges for anesthesiology].

PMID- 17436651
TI  - [Multicenter study of pain assessment in hospitals].
AB  - OBJECTIVE: To evaluate the recording of pain intensity in hospital charts.
      METHODS: A cross-sectional study was carried out in 15 hospitals in a sample of
      admitted patients with pain. Clinical data, including pain intensity, were
      gathered from the hospital records. Multiple analysis of variance was used to
      identify factors related to the intensity of pain recorded in the patients'
      charts. RESULTS: A total of 1038 patients with a mean (SD) age of 56.1 (18.9)
      years were included. Pain intensity was noted in the charts of 47.9% (95%
      confidence interval [CI], 44.9%-50.9%) of the patients. Pain intensity had been
      noted for 68.9% (95% CI, 61.4%-76.4%) of the patients with cancer, 43% (95% CI,
      38.2%-47.8%) of postoperative patients, 38.2% (95% CI, 35%-41.4%) of trauma
      patients, and 26.6% (95% CI, 16.9%-36.3%) of postpartum women. There was great
      interhospital variability. Factors associated with the recording of pain
      intensity in medical charts were hospital characteristics (large hospitals,
      teaching hospitals, hospitals and internal medicine and surgical specialities)
      and type of patient (cancer and trauma cases and patients reporting pain to the
      staff). CONCLUSION: There is inadequate written recording of intensity of pain in
      hospitals, even though there is considerable interhospital variation. Pain
      intensity assessment and recording is an indicator of quality of health care and
      should become a routine practice in hospital health care.

PMID- 17436652
TI  - [Incidences of early- and late-onset ventilator-associated pneumonia in a
      postanesthesia and critical care unit].
AB  - OBJECTIVES: To ascertain the frequency, risk factors, and causes of early- and
      late-onset ventilator-associated pneumonia (VAP) in a postanesthesia and critical
      care unit. MATERIAL AND METHODS: A prospective study was carried out between
      January 1, 1996 and December 31, 2001 of all ventilated patients staying longer
      than 48 hours in the critical care unit, with follow-up for 48 hours following
      discharge from the unit. Descriptive statistics were compiled for episodes of
      early- and late-onset VAP for a period of up to 4 days after intubation;
      univariate and multiple variable Cox regression analyses were also carried out.
      RESULTS: A total of 3614 patients were admitted to the unit (study cohort, 652
      patients). The mean length of stay in the unit for the study cohort was 13.64
      days. The most frequent diagnosis was multiple trauma (50.46%). The incidence
      density of VAP was 20.31 cases per 1000 patient-days on mechanical ventilation.
      The pathogens most often isolated in early-onset VAP cases were Staphylococcus
      aureus and Pseudomonas aeruginosa. In late-onset cases, the pathogens were
      Pseudomonas species. Early-onset VAP was 2.54 and 2.81 times more frequent in
      comatose and head-injury patients, respectively. Those rates were significantly
      different in late-onset cases. CONCLUSIONS: Early-onset VAP was more common in
      comatose and head-injury patients. The risk of developing late-onset versus early
      onset VAP was twice as great for postoperative patients.

PMID- 17436653
TI  - [Effect of tranexamic acid on postoperative bleeding in pediatric heart surgery].
AB  - OBJECTIVE: To assess the effects of a single dose of tranexamic acid on bleeding
      and requirement for blood product transfusion in children undergoing cardiac
      surgery with cardiopulmonary bypass. PATIENTS AND METHODS: A prospective study of
      closed cohorts undergoing pediatric heart surgery was carried out. The children
      weighed between 4 and 10 kg. Reoperated and cyanotic patients were included in
      the sample. The treatment group received 50 mg x kg(-1) of tranexamic acid before
      surgery. Analyzed data collected during the first 24 hours after surgery were
      biochemical parameters, bleeding, use of blood products, and D-dimer levels.
      RESULTS: Fifty-three patients, 25 in the treatment group, were enrolled. Patients
      on treatment had 24.8% less bleeding in the first 24 hours after surgery (P =
      .02). The transfusion of blood products was 20% less in the treatment group,
      although the difference was not significant except in the subgroup of patients
      who were reoperated. In that group the amount of blood products transfused was
      72% less than in the control group (P = .05). D-dimer levels were also lower in
      the treatment group (P = .003). No adverse effects attributable to the treatment
      were observed. CONCLUSIONS: A single preoperative dose of tranexamic acid to
      inhibit fibrinolysis reduces bleeding 24.8% in pediatric patients undergoing
      heart surgery with cardiopulmonary bypass. The effect is greater in reoperated
      patients, leading to a reduction in their requirement for transfusion. The use of
      this therapy in these patients is therefore highly justified.

PMID- 17436654
TI  - [Perioperative colloid administration: a survey of Spanish anesthesiologists'
      attitudes].
AB  - OBJECTIVES: To determine the availability of intravascular fluid volume
      replacement solutions in Spanish hospitals, to survey the extent of use of
      colloids by anesthesiologists, to ascertain the possible adverse effects they
      seek to prevent when using each solution, and to assess their level of knowledge
      about the subject. MATERIAL AND METHODS: A questionnaire was administered over a
      period of 6 months (July 2004-January 2005). The questionnaire was available
      online at www.encuestacoloides.com. The address was distributed by e-mail to
      anesthesiologists of all the Spanish autonomous communities and published in the
      Revista Espanola de Anestesiologia y Reanimacion. RESULTS: One hundred forty-two
      anesthesiologists responded. Crystalloids and colloids were widely available in
      most hospitals. Hydroxyethyl starch (HES) solutions were the colloids most often
      used (73%), followed by gelatins (28%). Dextran solutions, on the other hand,
      were no longer being used. The reasons the respondents gave for using these
      solutions were related to the time they remained in the vascular system, their
      greater effect of volume expansion, and the preservation of hemostasis. The most
      feared complication was anaphylactic reaction to gelatins and there were concerns
      about the dose limit for infusion of HES solutions and about hemodynamic
      instability caused by dextran solutions. Fifty-four percent felt that scientific
      meetings provide little information about colloids and volume replacement.
      CONCLUSIONS: There is widespread use of colloids other than dextran along with
      crystalloids for plasma volume replacement. Spanish anesthesiologists are clear
      about important concepts related to colloid use. However, a high percentage have
      doubts about certain fundamental issues. Continuing professional development
      opportunities related to intravascular fluid replacement therapy should be
      increased.

PMID- 17436655
TI  - [Bispectral index monitoring during intrahospital transport].
AB  - BACKGROUND AND OBJECTIVE: Risk of morbidity and mortality increases for
      critically ill patients during transfers within the hospital. Such patients often
      require sedation, and suboptimal sedation is associated with hypertension,
      tachycardia, and ventilator dyssynchrony. The aim of this study was to assess
      level of sedation as indicated by monitoring of the bispectral (BIS) index during
      intrahospital transport of critical patients. PATIENTS AND METHODS: Thirty
      patients who required transport to the critical care unit within the hospital
      were studied prospectively. We recorded time in transport, the agent used for
      sedation and the dosage, the BIS index, mean arterial pressure (MAP), and heart
      rate before starting transport and upon arrival at the critical care unit. The
      data were recorded by an observer who was not assigned to patient care. RESULTS:
      The mean (SD) transport time was 13.9 (4.2) minutes. Midazolam was used in 26
      patients and propofol in 4. Ten patients were given a bolus dose of cisatracurium
      before transfer started. Significant increases were observed in the BIS index
      (from 47 to 78, (P < .001), MAP (from 73 to 91 mmHg, P < .001), and heart rate
      (from 72 to 97 beats/min, P < .001) between the moment of starting transport and
      arrival at the critical care unit. Changes in the BIS index correlated
      significantly with changes in heart rate (r = 0.418, P = .024) but not with
      changes in MAP (r = 0.249, P = .19). CONCLUSIONS: Monitoring the BIS index during
      intrahospital transport of sedated, mechanically ventilated patients may be
      useful for detecting inadequate sedation.

PMID- 17436656
TI  - [Epidural fat in various diseases: contribution of magnetic resonance imaging and
      potential implications for neuro axial anesthesia].
AB  - Epidural fat is a reservoir of lipophilic substances that cushions the pulsatile
      movements of the dural sac, protects nerve structures, and facilitates the
      movement of the dural sac over the periosteum of the spinal canal during flexion
      and extension. Excessive epidural fat can compress the underlying structures,
      however, and affect the placement of catheters and the distribution of injected
      solutions. This review discusses changes in epidural fat related to various
      diseases and events: lipomatosis, epidural lymphoma, arachnoid cysts, epidural
      hematoma, meningiomas, angiolipomas, spondylolysis, scoliosis, spinal stenosis,
      and liposarcoma. Also discussed are the sequencing and protocols for magnetic
      resonance imaging that enable epidural fat to be observed and distinguished from
      neighboring structures. The relevance of epidural fat in spinal surgery is
      considered. Finally, we discuss the possible anesthetic implications of the
      abnormal deposition of epidural fat, to explain the unexpected complications that
      can arise during performance of epidural anesthesia.

PMID- 17436657
TI  - [Patient with postpartum seizures: differential diagnosis].
AB  - Pre-eclampsia is a serious obstetric complication associated with a high rate of
      maternal and fetal morbidity and mortality. We report the case of a woman with a
      medical history of insulin-dependent diabetes mellitus and seizures possibly
      related to hypoglycemia who was admitted for an emergency cesarian due to severe
      pre-eclampsia and macrosomic fetus. In the first hour after delivery she
      experienced loss of consciousness and seizure, with vaginal bleeding and
      hypovolemic shock. Maximum vigilance is required for a patient with several
      concomitant diseases and a high-risk pregnancy. All prophylactic measures to
      lower the risk to mother and fetus should be undertaken. We analyze preanesthetic
      assessment, differential diagnosis, and choice of anesthesia in relation to this
      case.

PMID- 17436658
TI  - [Cesarean section in a patient with acute myocardial infarction during
      pregnancy].
AB  - Maternal heart disease during pregnancy is the main cause of obstetric morbidity
      and mortality. We report the case of a 40-year-old woman with a history of
      myocardial infarction and percutaneous transluminal coronary angioplasty. The
      patient suffered a second heart attack and received pharmacologic treatment.
      After admission, she was seen to be 29 weeks pregnant. Delivery was by cesarean
      section under progressive epidural block without complications. We review the
      medical, obstetric, and anesthetic implications of myocardial infarction during
      pregnancy. The management of such patients should be multidisciplinary and
      decisions about delivery should be taken based on obstetric considerations.

PMID- 17436659
TI  - [Utility of magnetic resonance imaging in the diagnosis and follow-up of cerebral
      fat embolism syndrome].

PMID- 17436660
TI  - [Diagnosis of supraventricular tachycardia during surgical correction of pectus
      carinatum].

PMID- 17436661
TI  - [Bronchospasm after intubation in a morbidly obese woman who did not acknowledge
      a respiratory infection in the preoperative interview].

PMID- 17436662
TI  - [Unforseen difficult intubation related to an aberrant right subclavian artery].

PMID- 17436663
TI  - [Narcolepsy and anesthesia].

PMID- 17436664
TI  - [Management of difficult intubation with a ProSeal-type laryngeal mask for an
      emergency cesarean section].

PMID- 17436665
TI  - [Intravenous patient-controlled analgesia with remifentanil for labor and
      childbirth in a woman with multiple sclerosis].

PMID- 17436666
TI  - [Giant cervical mass in a premature neonate].

PMID- 17436667
TI  - [Interhemispheric subdural haematoma].
AB  - Interhemispheric subdural haematoma is considered to be rare finding even in the
      era of computer tomography. The aim of the paper is to present a group of 14
      patients (5 males, 9 females), average age 57.9 years, operated on for
      interhemispheric subdural haematoma, in all but one patient of traumatic origin.
      Symptoms related to the compression of medial cortex of cerebral hemisphere
      described as typical were not fully exacerbated in all patients. Falx syndrome as
      the sole manifestation was described in two patients, in other patients the
      clinical symptoms were determined by associated injuries. CT was the
      investigation of choice in all patients. Surgical evacuation of haematoma by
      means of parasagital osteoplastic craniotomy or burr hole trephination was used
      in all patients. Clinical outcome was determined by clinical condition on
      admission and the presence of haemorrhagic contusions. Another adversive
      prognostic factors were anticoagulation treatment or the presence of
      coagulopathy. It is mandatory to stress the possibility of sudden clinical
      worsening of initially conservatively treated patients.

PMID- 17436668
TI  - [The isolated internal iliac artery aneurysms].
AB  - The isolated iliac artery aneurysm is a rare disease. Diagnosis and treatment of
      these aneurysms according to their anatomic location is difficult. Authors
      describe diagnostic-therapeutic approach in the care of three patients at the
      vascular unit of the Surgical Clinic of the Teaching Hospital in Presov. They
      analyze different methods of treatment with emphasis on endovascular therapeutic
      methods mainly in the therapy of polymorbid high risk patients.

PMID- 17436669
TI  - [Embolic complication of the postcathetrization femoral artery pseudoaneurysm
      treatment using percutaneous thrombotization. A case review].
AB  - Considering frequencies of the heart cathetrization procedures, including
      treatment of pseudoaneurysms of the femoral artery using percutaneous
      thrombotization, a possibility of peripheral arterial emobolization should be
      considered. The authors describe management of the relatively rare complication
      in the treatment of postcathetrization pseudoaneurysms. According to the case
      review, clearing the obliterating arterial embolus of the tissue glue is
      technically feasible even more than 24 hours folowing the embolization.

PMID- 17436670
TI  - [Ruptured infectious pseudoanerysm of the superficial femoral artery: literature
      overview and a case review].

PMID- 17436671
TI  - [Endovenous laser photocoagulation of the insufficient saphenous vein in
      experiment].
AB  - AIMS: The endovenous laser treatment of varicose veins has been using for several
      years throughout the world with clinical results comparable to traditional
      surgery. Nevertheless, many controversies still exist in the world literature in
      terms of parameters of laser generator and procedure itself. The aim of this
      laboratory study was the standardisation of the procedure and set-up of the
      optimal technical parameters to achieve maximal vein shrinkage as basic marker of
      successful long-term result. MATERIAL AND METHODS: The insufficient trunks of the
      long saphenous veins which were stripped during the traditional Babcock's
      stripping procedure, were irradiated with the laser energy delivered by the diode
      generator emitting 980 nm laser beam in the laboratory settings. In total, 279
      vein segments were treated. We used the power of 5W, 8W, 10W, 12W and 15W during
      the maximal time possible to achieve the maximal shrinkage of the saphenous vein
      with minimal number of perforations. The study cohort consisted of two groups -in
      the first group the veins were filled with the blood (n = 139), in the other one
      the veins were empty (n = 140) to simulate the patient's position on the
      operating table. After the procedure, every vein segment was cut longitudinally,
      unfolded and its inner circumference was measured and compared to inner
      circumference of untreated part of the same venous segment. RESULTS: Maximal
      shrinkage and minimal number of perforations were achieved using lower or medium
      power (8 to 12 W). Circumference of shrunken vein compared to normal venous
      circumference (100%) was as follows: 50% (power 5W), 45% (power 8W), 40% (power
      O1W), 45% (power 12W) and 58.6% (power 15W). These differences are statistically
      significant (p < 0.001). When higher power was used (15W), the perforations and
      carbonisations were more frequent and total energy was lower but the difference
      in amount of energy delivered was not significant (p = 0.379). CONCLUSIONS:
      Shrinkage of the vein depends on laser power. Based on our experiments, we
      recommend photocoagulation with lower or medium power (8 to 12 W) and slower pull
      back (0.2 to 2 mm/s) to achieve the sufficient energy per centimeter of the vein
      and the optimal long-term outcome.

PMID- 17436672
TI  - [Multiple lung metastasectomy for the poor differentiated metastatic synovial
      sarcoma].
AB  - OBJECTIVES: Synovial sarcoma is the rare indication for the pulmonary
      metastasectomy due to its aggressive biologic behavior and early dissemination.
      The radical surgical approach in therapy of the multiple pulmonary metastases
      could improve quality of life and median survival in carefully selected patients.
      METHODS: From the group of 7 patients with the lung metastases of the synovial
      sarcoma operated in our department during the last 5 years we are presenting the
      case of the 39 years old man with the previous history of the surgical removal of
      the synovial sarcoma near the cubital fossa one year before. Considering the
      lungs as the only organ involved, bilateral complete metastasectomy through
      muscle sparing vertical thoracotomies was done. There were 12 metastases from all
      lung lobes with the exception of the right middle lobe. Analysis of the
      pathologist showed biphasic metastatic synovial sarcoma with the high mitotic
      activity. The 6 cycles of the MAID regime succeeded. RESULTS: Median survival of
      the whole group is 25 months, there are 3 patients alive. In the above mentioned
      patient 1 year after the metastasectomy PET-CT showed focus of the 4th left rib
      suspected to be malignant. Wide resection of the rib was done, but no malignancy
      was disclosed, there were only reparative changes. The patient has been tolerated
      the oncological treatment very well and 45 months after the lung metastasectomy
      there are no sings of a malignant disease. CONCLUSION: Lung metastasectomy of the
      multiple lung metastases of the synovial sarcoma is of value despite of uncertain
      long-term prognosis. It is recommended to consider the metastasectomy even in low
      differentiated tumors. The prerequisite for the effective treatment is a complete
      resection.

PMID- 17436673
TI  - [Laparoscopic liver resection].
AB  - Rapid development of liver surgery in the last 25 years results from introduction
      of new procedures entailing an increase in the number of operated patients, and
      simultaneously a reduction in risk of the surgery and subsequent postoperative
      morbidity and mortality. They include standard preoperative examination completed
      by new high-resolution diagnostic methods (duplex ultrasound, spiral CT, liver
      scintigraphy, PET) which can better reveal the pathological focus in relation to
      liver anatomy and largely contribute to the consideration of resecability of the
      liver affection . Standard resection technique is, in addition to the advantage
      of an anatomical resection, completed with modern technology which helps to
      reduce the blood loss and ischemic damage to the remaining liver parenchyma
      especially in non-anatomical resections. Nowadays, liver resections are performed
      by a combination of various techniques. One of them is a liver parenchyma
      resection using a harmonic scalpel in the classical surgical procedure. There are
      also mini-invasive laparoscopic operations, and recently robotic resections which
      can't be done without the harmonic scalpel. The authors present a case report of
      a 25-year-old woman who developed spastic pain in the epigastrium three years
      ago. Sonography, CT, MR, liver scintigraphy and, last but not least, diagnostic
      laparoscopy were used for accurate diagnostics. Diagnostic laparoscopy was
      performed in order to confirm the diagnosis, extent of surgery and especially the
      possibility of performing laparoscopic liver resection. This was carried out
      using the harmonic scalpel which is the method of choice especially in non
      anatomical resection for better control of bleeding and safer isolation of bile
      ducts and vessels.

PMID- 17436674
TI  - [Appendectomy--comparison of results of laparoscopy versus open surgery].
AB  - AIM: The authors present results of laparoscopy versus open appendectomy in
      patients indicated for urgent procedures. MATERIALS AND METHODS: 214 patients,
      who underwent urgent appendectomy during a 18-month period (November 2004 - April
      2006) were included in the retrospective study. The subjects were assigned to two
      main study groups according to the chosen abdominal approach - laparoscopic
      versus classical method. Within the respective study groups, duration of the
      procedure, histopathological findings, peroperative and postoperative
      complications, duration of postoperative hospitalization were assessed.
      Furthermore, in the laparoscopic subgroup, requirement for conversion to open
      surgery is assessed. RESULTS: The results proved that the laparoscoic approach
      reduced hospitalization period in patients with histopathologicaly advanced
      findings. The positive effect of miniinvasive methods on hospitalization duration
      is diminished in subjects with less advanced findings. CONCLUSION: Considering
      overall benefits of the laparoscopic procedures, the authors themselves prefer
      the laparoscopic method as the method of choice in management of acute
      appendicitis.

PMID- 17436675
TI  - [Portal vein embolization--increased chance for liver resecability for
      malignancies].
AB  - INTRODUCTION: Liver surgery for liver malignancy is recently limited not by
      technical possibilities but by physiological reserves of liver parenchyma. Portal
      vein embolization (PVE) is performed to increase future liver remnant volume
      (FLRV) to extend the possibilities of liver resections. The authors evaluate the
      cohort of patients, that underwent PVE and confront them with the cohort of
      patients that underwent liver resection without PVE. METHODOLOGY: At the
      Department of Surgery and Departement of Radiology, University Hospital Pilsen
      there were performed successfully PVE at 24 patients between January 2001 and
      August 2006. The increase of FLRV was sufficient at 17 patients. The mean period
      between PVE and computed tomography volumetry was 29 days. The mean period
      between PVE and surgical procedure was 54 days. 8 patients underwent radical
      liver surgery (right hepatectomy, extended right hepatectomy, combination of
      right hepatectomy with RFA in left lobe), 3 patients underwent radiofrequency
      ablation, the rest of patients was explored. For comparison we used cohort of 107
      patients that underwent one step radical surgery for malignancy. RESULTS: 1 year
      survival rate after liver operation was 85.7%, 3 years survival rate 42.9%.
      Disease free interval (DFI) was counted only for group of radicaly operated
      patients. One year DFI was 40%, two year DFI was 20%. The number of leasions was
      not proved as statistically significant for DFI or survival rate. In non PVE
      group 1 year survival rate was 78.9%, 3 years survival rate was 34.0%, one year
      DFI was 60.2%, two years DFI was 36.6%. DISCUSSION: The survival rate was higher
      in PVE group, the DFI was shortened in PVE group. In our cohort we could
      conclude, the PVE increase survival rate instead of shortened DFI. PVE spreads
      possibilities for liver resections at patients with small FLVR and enables
      radical surgical therapy for patients, that will be leaved a palliative surgery
      or oncological therapy.

PMID- 17436677
TI  - [Laparoscopic diagnostics of the acute bowel ischemia--first experimental
      experience].
AB  - AIM: Aim of the study was to prove possibilities of laparoscopic diagnostics of
      an acute bowel ischemia when using fluorescein dye and the ultra-violet (UV)
      light. MATERIAL AND METHODS: There were five animals (domestic pigs) included
      into the experiment in the year 2005. The endoluminal embolization of the
      peripheral branch of superior mesenteric artery (SMA) was made. Optical filters
      were placed to laparoscopic set to produce UV light. Fluorescein was administered
      intravenously and bowel inspection and applying the clips on the border of
      ischemia visualized by fluorescein was performed. RESULTS: In all cases, the
      combination of laparoscopy, UV light and fluorescein dye distinguished ischemic
      part of bowel from the viable remnant. CONCLUSION: Combination of the UV light
      and fluorescein dye is able to reliable differentiate the viable segments of the
      bowel from the ischemic ones.

PMID- 17436676
TI  - [Biliary ileus--a missed cause of intestinal obstruction].
AB  - INTRODUCTION: Biliary ileus is a rare complication of cholelithiasis, counting
      for 1-4% of all intestinal obstructions. The aim of the work is to summarize
      diagnostic and treatment options, assess significance of laparoscopy in this rare
      form of ileus, based on the authors' own experience and available literature.
      PATIENTS AND METHODS: The retrospective study analyzed data of patients operated
      for biliary ileus in the Surgical clinic of the Faculty Hospital in Ostrava
      during 2002-2006. The following criteria were assessed in the patient group
      including 9 subjects: gender, age, secondary disorders. ASA (American Society of
      Anesthesiologists) classification of the subjects, symptomatology, results of
      preoperative visualization methods examinations and intervals between the disease
      onset and the procedure. The following peroperative data were collected: duration
      of the procedure, type of the procedure, complications, obstruction site and
      concrement size. Duration of postoperative hospitalization and complications
      arising during this period were recorded. RESULTS: Concrements were extracted
      through laparotomy in 5 patients, in 3 subjects the procedure was conducted
      laparoscopically. In 1 subject, the concrement extraction procedure was conducted
      together with cholecystectomy and a cholecystoduodenal fistule closure. No
      complications were recorded peroperatively, in case of the laparoscopic
      procedure, conversion was not requred. Obstruction site was localized on the
      jejunum in 3 subjects, on the ileus in 6 subjects. The concrement size ranged
      from 2x3 cm to 4x6 cm. The mean procedure duration was 61 minutes. The median of
      postoperative hospitalization was 12 days. During the postoperative period,
      complications were recorded in 6 subjects, 1 patient exited due to multiorgan
      failure. CONCLUSION: Early timely diagnostics with a significant role of the CT
      examination is inevitable in patients with rare forms of intestinal obstruction.
      Adequate surgical management considering the patient's overall condition must be
      introduced. Taking into consideration the patients age and their polymorbidity,
      extraction of concrements via enterotomy remains the method of first choice.
      Duration of postoperative hospitalization depends on frequent complication rates.

PMID- 17436678
TI  - Developing a cash up-front program.

PMID- 17436679
TI  - UB-04 crosswalk rules: is your organization ready?

PMID- 17436680
TI  - Going after the 'hired guns': is improper expert witness testimony unprofessional
      conduct or the negligent practice of medicine?

PMID- 17436681
TI  - [Aptamers as perspective affine reagents for clinical proteomics].
AB  - Application of proteomic results to scientific and medical practice will depend
      in many respects on progress of affine microchips technologies that determine the
      continuous search for inexpensive and robust affine reagents alternative to
      monoclonal antibodies. Among synthetic mimetics of antibodies, the
      oligonucleotide aptamers are of the greatest interest as affine reagents due to
      the possibility to automate their selection and due to the low cost of
      oligonucleotide synthesis. In the review the problems related to the automation
      and optimization of aptamer selection and to the selection of photoaptamers
      capable to formation of photo-induced covalent complexes with protein targets
      have been considered. The existing approaches to the post-selection modification
      of the aptamers to increase theirs affinity and selectivity to protein targets
      are discussed.

PMID- 17436682
TI  - [Iron metabolism in biological systems (biochemical, pathophysiological and
      clinical aspects)].
AB  - Modern concepts concerning iron metabolisms in the body, its circulation,
      involvement into free radical processes and lipid peroxidation (LP) are reviewed.
      Spetial attention is paid to cytotoxic effects, Fe2+ influence on lipid
      peroxidation, its role in multiple organ failure development in critical states.
      Iron ion can be bound by desferal, which may be effectively used for intensive
      care of critical states.

PMID- 17436683
TI  - [Potentiation of NO-dependent activation of soluble guanylate cyclase by
      polyamines].
AB  - The influence of polyamines (putrescine, spermidine, spermine) on the activity of
      human platelet soluble guanylate cyclase and stimulation of the enzyme by sodium
      nitroprusside, YC-1 and their combination was investigated. All polyamines used
      stimulated the guanylate cyclase activity and potentiated its activation by
      sodium nitroprusside. The stimulatory effects of sodium nitroprusside and
      putrescine (or spermine) were additive; spermidine produced a synergistic
      activation and increased the additive effect. All polyamines investigated
      inhibited the activation of the enzyme by YC-1 and decreased the synergistic
      activation of sodium nitroprusside-stimulated guanylate cyclase activity by YC-1
      with approximately the same efficiency. The revealed ability of polyamines
      investigated to potentiate and synergistically increase (similar to YC-1, but
      less effective) NO-dependent activation of soluble guanylate cyclase represents a
      new biochemical effect of these compounds, which should be taken into
      consideration, especially due to the endogenous nature of polyamines. The data
      obtained suggest, that the specific functions of polyamines in the processes of
      cell growth and diffentiation may be also related to the ability of these
      compounds to activate soluble guanylate cyclase and increase cGMP level.

PMID- 17436684
TI  - [Changes in lipids of granulation fibrous tissue in rats at various doses and
      routes of melatonin administration].
AB  - The experimental data indicate that melatonin actively influences time-causes of
      changes of lipid content in rats tissue during the inflammation process. Its
      effect depends on a dose, modes of administration (intraperitonial, hypodermic or
      local) and duration of treatment. A single dose intraperitonial administration of
      melatonin (4 mg/kg) did not influence lipid content in the granular-fibrose
      tissue, while repeated injections of this hormone limited the increase in
      contents of lipids and phospholipids at the 5th and 8th days of regeneration.
      Long-term subcutaneous injections of melatonin caused distinct changes of lipids:
      at the dose of 0.3 mg/kg it prevented, and at the dose of 4 mg/kg it promoted the
      increase of lipid content in the granular-fibrose tissue. Local application of a
      melatonin solution (1.5 mg/ml) at early periods of regeneration caused
      insignificant changes of total lipids and total phospholipids in the granular
      fibrose tissue. However, the higher concentration (15 mg/ml) of melatonin caused
      the decrease of total lipids due to reduced content of cholesterol and
      triglycerides and the increase of total phospholipids and some of their
      fractions.

PMID- 17436685
TI  - [Analysis of effectiveness of intracellular permeability of ivermectin
      immobilized on corpuscular carriers].
AB  - Penetration of ivermectin adsorbed on the surface of colloidal gold particles or
      included in micelles to phagocytic immune system cells was studied. Detection of
      the preparation in the cells was carried out by an immunochemical method,
      employing miniantibodies to ivermectin obtained from a combinatory phage library
      and by a chromatographic method on the HPLC system "Stayer". It was found that
      ivermectin adsorbed on colloidal gold particles was accumulated in the cells most
      intensively.

PMID- 17436686
TI  - [Inhibition of bacterial lypopolysaccharide-induced inflammation by oxidized
      lipids].
AB  - Previous studies demonstrated that oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero
      3-phosphorylcholine inhibits inflammatory effects of the bacterial
      lipopolisacharide (LPS, endotoxin). In this work we have characterized the anti
      endotoxin activity of other classes of oxidized phospholipids with different
      polar head groups and fatty acid residues. LPS-induced expression of E-selectin
      on human endothelial cells was inhibited by oxidized phosphatidylcholine,
      phosphatidylserine, phosphatidylethanolamine, and phosphatidic acids. The anti
      endotoxin effect insignificantly depended on the type of polyunsaturated fatty
      acids. Unoxidized phospholipids did not suppress effects of LPS. Thus, the anti
      endotoxin activity of oxidized phospholipids crucially depends on the presence of
      oxidatively modified fatty acid residue.

PMID- 17436687
TI  - [Effect of Zn(II) and Mn(II) on catalytic activity of aspartic proteinases from
      Candida albicans].
AB  - The interaction of secreted aspartic proteinases Candida albicans (SAP C.
      albicans) with ZnCl2 and MnCl2 was studied. Logarithms of stability constant from
      the data of electronic spectroscopy were calculated: lgbeta = 4.73 +/- 0.20 for
      the complex [SAP C. albicans - Zn(II)] and lgbeta = 7.02 +/- 0.20 for the complex
      [SAP C. albicans - Mn(II)]. The composition and maximum accumulation of complexes
      in solution were calculated. The optimal conditions of hydrolysis of the
      substrate, HAS (human serum albumin) in the presence of proteinases were
      determined: [HSA] = 0.004 g/ml, [SAP] = 2.33 microM, pH = 4.5, the time of
      incubation of 25 min. The activity SAP C. albicans in the presence of ZnCl2 and
      MnCl2 in different concentrations in optimal conditions of enzymic hydrolysis was
      estimated. For the first time the activating action of ZnCl2 on catalytic
      activity of proteinase in concentration 5 x 10(-7) mol/l was discovered. The
      maximal rate of enzymic reaction (Vm), the Michaelis constant (Km) and constants
      of effects in presence and absence as the effector of ZnCl2 were calculated. The
      estimation of albuminatic activity of C. albicans infections family in different
      diseases localization in the presence and the absence as the effector of ZnCl2
      was evaluated.

PMID- 17436688
TI  - [Production and reception of growth factors in the placenta during physiological
      and gestosis complicated pregnancy].
AB  - 30 women with physiological pregnancy and 28 women with gestosis were examined.
      In the early chorion obtained after abortion and on the full-term placenta the
      content of the epidermal growth factor (EGF), vascular-endothelial growth factor
      (VEGF) and their receptors were studied by means of the ELISA method. In the
      process of normal gestation the increase of the placental production both of the
      EGF and VEGF was found. During the pregnancy complicated with gestosis and
      miscarriage in the first trimester the content of EGF and its receptor was lower
      compared to the physiological values. For VEGF and its receptor opposite changes
      were found: the increase of quantity of the growth factor and the decrease of its
      receptor. In the case of gestosis and term pregnancy the content of the both
      growth factors and their receptors was lower than in controls. The revealed
      changes in production of the angiogenic growth factors and their receptors in the
      placenta may have the pathogenic importance in the development of gestosis.

PMID- 17436689
TI  - [Glutathione system in erythrocytes and plasma in viral hepatitis].
AB  - In all 5 acute (AVHs) and chronic viral hepatites (CVHs) there was the increase
      of erythrocyte activities of glutathione peroxidase (GPx) and glutathione
      reductase (GR), and the decrerase in GSH concentration. In blood plasma there was
      accumulation of GPx, glutathione S-transferase (GST) and y-glutamyl transferase
      (gammaGT). GSH and GR increased in plasma only in AVHs. In CVH C erythrocyte GST
      increased. Evidently changes in the erythrocyte glutathione system are reactions
      to oxidative stress and in blood plasma they are consequences of inflammation and
      hepatocyte cytolysis. Changes were more pronounced in middle-heavy course than in
      the heavy one. These changes have pathogenic importance and can be used in
      addition to complex diagnostics. They are significantly differed from changes in
      chronic gall-bladder diseases. Necessity of separate investigation of glutathione
      system in erythrocytes and blood plasma but not in whole blood is argued.

PMID- 17436690
TI  - [The method for detection of protein oxidability in serum and plasma].
AB  - Copper-induced oxidability of proteins was investigated in plasma and serum of
      blood of healthy donors. Incubation of plasma and serum samples with copper ions
      was accompanied by accumulation of carbonyl products of oxidized proteins.
      Quantity of the formed carbonyl products depended on both time of incubation, and
      dilution of plasma and serum. Under identical conditions of oxidation the
      accumulation of carbonyl products in serum of blood was higher than in plasma.

PMID- 17436692
TI  - [Ways of optimizing the use of the new equipment delivered within the framework
      of the priority national "Health" project to clinical and diagnostic
      laboratories].

PMID- 17436691
TI  - [Modification of recombinant asparaginase from Erwinia carotovora with
      polyethylene glycol 5000].
AB  - A method for polyethylene conjugation with recombinant asparaginase has been
      developed to improve therapeutically important properties of this enzyme. Methoxy
      nitrophenyl carbamate of polyethylene glycol with molecular weight 5000 was
      employed as the modification reagent. Optimization of pegylation procedure
      allowed achieving high level of the enzyme modification. Under 4.5 molar excess
      of modification reagent more than 10 molecules of methoxy-polyethylene bound per
      one asparaginase molecular. The modified asparaginase retained 57% of initial
      activity. A simple and efficient pegylation procedure described in this work can
      be used for asparaginase production with improved therapeutic properties.

PMID- 17436693
TI  - [Modernization of public health care: the contribution of the Department of
      Clinical Laboratory Diagnosis in the training of a general practitioner].

PMID- 17436694
TI  - [Capabilities of hematological analyzers].

PMID- 17436695
TI  - [Experience with a Russian MiniGem hemoglobinometer].

PMID- 17436696
TI  - [Adaptation of Russian reagents to hematological analyzers].

PMID- 17436697
TI  - [Intralaboratory control of enzyme immunoanalyzers].

PMID- 17436698
TI  - [Differential sensitivity of peripheral blood granulocytes, monocytes, and
      lymphocytes to endotoxin-induced apoptosis in patients who have sustained
      Salmonella infection].
AB  - The differential sensitivity of peripheral blood granulocytes, monocytes, and
      lymphocytes to endotoxin-induced apoptosis was studied in convalescents with
      Salmonella infection. The number of early (Tunel+PI-) and late (Tunel+PI+)
      apoptotic cells and the rate of apoptosis (the relative content of DNA apoptotic
      fragments in the solitary cell) were determined on a FACSCalibur cytofluorometer,
      by applying a package of the CellQuest programs (Becton Dickinson). A higher
      threshold of sensitivity of granulocytes, monocytes, and lymphocytes to the
      apoptotic effect of low, suboptimal doses (100 ng), as well as suppression of
      early stages of apoptosis by the optimal doses (1000 ng) of S. enteritidis
      lypopolysaccharides (LPS) were observed in patients who had sustained
      salmonellosis at a stage of reconvalescence. The hierarchy of LPS-induced
      apoptosis (granulocyte--monocyte--lymphocyte), observed in healthy donors, was
      also retained in the group of patients receiving the suboptimal doses of LPS,
      which seems to be associated with the repeated action of toxin on sensitized cell
      populations.

PMID- 17436699
TI  - [Nitric oxide in endothelium-dependent vasodilatation. Bases of the unity of the
      endothelium and smooth muscle cells in paracrine metabolic regulation].

PMID- 17436700
TI  - [Immunohematological studies in clinical practice (a lecture)].

PMID- 17436701
TI  - [Endothelial injury markers as a possible criterion for the efficiency of
      treatment for arterial hypertension].
AB  - Endothelial injury markers, including endothelial microparticles (CD31+
      particles, 1.5-4.0 microm in diameter), von Willebrand factor, endothelin-big 1
      38, and plasma concentrations of thiobarbituric acid reactive substances in
      patients with essential hypertension (EH), were evaluated. The endothelial injury
      markers and the concentrations of thiobarbituric acid reactive substances were
      significantly elevated in patients with EH, as compared to healthy subjects and
      decreased, so was blood pressure in response to antihypertensive pharmacotherapy.
      However, the patients and the healthy subjects had differences in these
      parameters. It is suggested that all the studied parameters of endothelial injury
      are suitable for laboratory monitoring of treatment in patients with EH in
      different periods of the disease, including a stable blood pressure period.

PMID- 17436702
TI  - [Lipid peroxidation and the antioxidative system in chronic Lyme borreliosis].

PMID- 17436703
TI  - [Some aspects of human mineral metabolic disturbances in viral hepatitis of
      various genesis].
AB  - A new prognostic criterion was developed to evaluate the severity of different
      forms of viral hepatitis, by studying zinc metabolism. In patients with viral
      hepatitis, zinc metabolic disturbances were ascertained to occur concurrently
      with pigment, protein, and carbohydrate metabolic disturbances, an increase in
      the activity of some serum enzymes (glutamine alkaline transferase, glutamine
      pyruvate transferase, alanine aminotransferase), and a reduction in hepatic
      antitoxic function. The indicator of normalization of zinc metabolism may be an
      additional prognostic criterion for evaluating the full recovery of a patient.
      The studied criterion enables the chronic pattern of viral hepatitis to be
      predicted in convalescents after their discharge from hospital.

PMID- 17436704
TI  - [Evaluation of exocrine function of the pancreas in patients with viral hepatitis
      B and/or C].

PMID- 17436705
TI  - [Laboratory technology for detection of NO-synthase activity].

PMID- 17436706
TI  - [Overview of the 10th All-Russian Scientific Forum with the international
      participation of the "Immunology Days in Saint Petersburg" named after
      Academician V.I. Ioffe].

PMID- 17436707
TI  - [The results and aims of Russian Federation Armed Forces medical service
      activities].
AB  - In the past year the main efforts were concentrated on bringing the medical
      service staff and structure into line with the Armed Forces fighting staff and
      the problems being solved. The medical forces and means of permanent battle
      readiness have gotten the further development. The system providing the medical
      equipment and property was subjected to radical reorganization. The normative-and
      law basis of military health service was improved and the licensing of military
      medical institutions' activities including those stationed outside the Russian
      Federation was conducted. The significant result of 2006 was the approval of a
      Conception of military medical service regular policy, the main principles of
      which are the openness, the scientific substantiation of quantitative and
      qualitative characteristics of medical staff and the rise of military medical
      service prestige. In 2007 the main aims of medical service are connected with the
      problems of battle and mobilization readiness, organizational construction,
      treatment-and-prophylactic support, troop sanitary-and-epidemiological safety,
      regular work and military medical education.

PMID- 17436708
TI  - [The perspectives of bringing up to strength the posts of armed forces medical
      service troop link by graduates from civil medical higher schools (the data of
      sociologic investigation)].
AB  - To predict the possibilities of use of graduates from civil medical higher
      schools for bringing up to strength the posts of Russian Federation Armed Forces
      medical service troop link the sociological cross investigation was conducted.
      The poll by questionnaire was used in 7522 students of both sexes from 35 Russian
      civil higher schools. The results of investigation have shown the presence of
      reserve for bringing up to strength the posts of army and navy medical service at
      the expense of students from civil higher schools. The rise of social
      attractiveness of military service by solving the problems socially significant
      for responders will allow providing the necessary competition among the
      candidates for substitution of officers' posts--military physicians. At the same
      time the specific character of military physicians' activities requires the
      maintenance and further development of its own successfully functioning system
      for specialists' training.

PMID- 17436709
TI  - [About some perspective directions of suicide prophylaxis among the servicemen].

PMID- 17436710
TI  - [The experience of use of transcutaneous dynamic electroneurostimulation with the
      help of apparatus "DiaDense-PK" in the complex treatment of diseases and
      traumatic injuries of locomotor and peripheral nervous system].

PMID- 17436711
TI  - [Simultaneous operations for cholelithiasis].

PMID- 17436712
TI  - [The specific features of coronary disease course against the background of
      connective tissue undifferentiated dysplasia syndrome].

PMID- 17436713
TI  - [Clinical picture and treatment of panic disorder accompanied with generalized
      anxiety].

PMID- 17436714
TI  - [The clinical and pharmacoeconomic aspects of gemifloxacin(corrected) use in the
      patients with extra-hospital pneumonia in stationary conditions].

PMID- 17436715
TI  - [The influence of highly intensive aviation noise on hemodynamic indices in air
      forces engineering-and-technical staff].

PMID- 17436716
TI  - [About restorative therapy of flying staff with the use of ozone].

PMID- 17436717
TI  - [Evaluation of state and developmental perspectives of an armored medical
      automobile fleet].

PMID- 17436718
TI  - [An outstanding field surgeon (devoted to th 240th anniversary of D. Larrey's
      birth].

PMID- 17436719
TI  - [Sanitary education of army and fleet personnel (brief historical essay)].

PMID- 17436720
TI  - [Ecological bases of the combination of natural foci of Trematoda infections in
      the floodplain-river ecosystem of the Konda River. Communication 2. Host
      population-combined foci of Trematoda infections].
AB  - In the context of the present-day teaching of parasitocenoses and the proposition
      that the pathogen's population is the only compulsory and specific component of a
      natural focus, the author discloses the ecological bases of the combination of
      natural foci of opisthorchiasis and methorchiasis (M. bilis), methorchiasis (M.
      bilis) and methorchiasis (M. xanthosomus). These foci are host population
      combined. While analyzing the combination of foci, it is expedient to consider
      them in pairs since this provides a way of identifying only the combination bases
      that are unique to these foci. The parasitic systems of flukes, the
      parasitocenoses of co-acting parasitic systems of "twin types", the structure of
      foci, the species-specific composition of ecosystems, and the ecological
      relations of the Opisthorchis fluke hosts act as the biotic bases of a
      combination of foci of Trematoda infections. By coinciding, the multihost
      hemipopulations of parasites and the susceptibility of host populations
      predetermine the combination of Opisthorchis fluke foci. The susceptibility of
      hosts, the multihost pattern of Opisthorchis flukes, the identity of parasitic
      systems, and the common mechanism of pathogen transmission act as the epizootic
      bases of a combination of invasion foci. The morphological structure and
      hydrological regime of a landscape act as the abiotic bases of a combination of
      foci. The hydrological regime is by its nature a universal mechanism of pathogen
      transmission. The foci of Opisthorchis flukes at the level of parasitocenosis of
      metacercarium populations and fish populations in the Konda River ecosystem are
      combined in the age groups of only carp (Cyprinidae) underyearlings and
      yearlings. The abiotic, biotic, and epizootic bases of a combination of natural
      foci of Opisthorchis flukes are, in the aggregate, the ecological bases of a
      combination of foci.

PMID- 17436721
TI  - [The body's responsiveness and the efficiency of antihomotoxic therapy for
      chronic opisthorchiasis: an aggregate clinical estimate].
AB  - The authors have proposed an extended clinical evaluation system that calls for a
      study of the mechanisms of development and relationships of any symptoms and
      diseases, including those unrelated to opisthorchiasis. Forty patients who had
      been diagnosed as having chronic opisthorchiasis and had a long history were
      examined. There was a drastic reduction in the body's susceptibility to acute
      inflammations during progressive chronic degenerative diseases just at the age of
      17-30 years, which is indicative of systemic responsiveness abnormalities. The
      practical application of the proposed aggregate clinical estimate system makes it
      possible to apply a holistic approach to analyzing the patients' health status,
      to substantially upgrade the quality of clinical diagnosis, and extend the
      capabilities of a differential approach to evaluating the severity of disease and
      planning therapy.

PMID- 17436722
TI  - [Intestinal protozoa in children of child day care centers and orphanages of
      Moscow].
AB  - On the basis of an analysis of the contamination with intestinal protozoa in 373
      Moscow children and comparison of the data of a randomized protozoological study
      of matched groups of 543 children from three towns of the Russian Federation in
      the past 15 years, the authors revealed profound changes in the pattern of
      intestinal parasitocenosis in the examinees: preponderance of B. hominis recently
      reclassified as a protozoan in all groups of examinees; a reduction in the
      detectable protozoan types up to a single type both among parasitic amoebas (E.
      coli) and flagellates (L. intestinalis). The incidence of giardiasis among the
      children's collective bodies averaged 3.5% and that in the kindergartens was
      0.5%.

PMID- 17436723
TI  - [Parasitic diseases in children in the out- and inpatient settings in Dagestan].

PMID- 17436724
TI  - [The current canine and feline parasitic diseases situation in the megapolis of
      Moscow].
AB  - The paper describes the epizootic situation associated with parasitic diseases in
      dogs and cats in the megapolis of Moscow. The situation becomes particular
      dangerous in the dogs kept in the flats of the city's dwellers wherein 30 (28%)
      out of the 107 dogs examined have been found to be infested with T. canis, T.
      leonine, T. vulpis, Taenia sp., D. caninum, and two protozoan species:
      Cystoisospora canis and C. ohioenensis. Out of the 80 cats examined, there are 22
      (27.5%) infested cats. T. mystax, T. leonine, Taenia sp., and Cystoisospora felis
      are detectable in this group of the animals. This situation constitutes a serious
      hazard in the infection of the city's population with zoonoses.

PMID- 17436725
TI  - [Diagnostic efficiency of enzyme immunoassay system based on the recombinant
      antigen EgF in sheep larval hydatid disease (echinococcosis)].
AB  - The paper presents the results of designing a technology for the manufacture of
      enzyme immunoassay kits to detect class G antibodies to the Echinococcus
      granulosus antigen EgF with a molecular weight of 16.7 kDa in sheep. According to
      the results of field trials on flocks of sheep from various age groups, the
      diagnostic efficiency of the test system was 78.1% sensitivity and 73.9%
      specificity. The proposed test system may be used during mass sheep screenings
      for the epizootic monitoring of the prevalence ofechinococcosis in the Russian
      Federation, for the serological diagnosis of this disease in the female livestock
      at the level of a flock.

PMID- 17436726
TI  - [Opisthorchiasis in the Kemerovo Region].
AB  - In the Kemerovo Region, the incidence of opisthorchiasis increased among adults
      and children from 44.0 in 1995 to 78.2 per 100,000. The high risk of Opisthorchis
      infection in children aged less than 14 years has recently increased from 17.2 to
      35.0.

PMID- 17436727
TI  - [A role of plant products in the transmission of causative agents of helminthisms
      in the Republic of Tadjikistan].

PMID- 17436728
TI  - [Methods for disinvasion of liquid and solid waste in the Republic of
      Tadjikistan].

PMID- 17436729
TI  - [Morphological and genetic characteristics of the malarial mosquito Anopheles
      beklemishevi (Diptera, Culicidae)].
AB  - The paper presents morphological and genetic data on the malarial mosquito
      Anopheles beklemishevi Stegnii et Kabanova, 1976. It also provides morphological
      accounts of eggs, age stage IV larvae, and, firstly, pupae and imagoes. The paper
      considers it possible to use cytogenetic and molecular markers to identify An.
      beklemishevi.

PMID- 17436730
TI  - [Biochemical characteristics of ticks of the families Argasidae and Ixodidae].
AB  - Polyacrylamide gel electrophoresis was used to study homogenate supernatants from
      the bloodsucking ticks (Argasidae and Ixodidae) belonging to 8 different genera
      and species. Differences were found in the electrophoretic mobility of protein
      fractions in adult ticks of these two different families and between several
      genera of Ixodes ticks (such as Haemaphysalis, Hyalomma, Dermacentor,
      Rhipicephalus and Ixodes). Argasidae ticks were found to have generic and even
      species-specific differences at the nymphal stage of development. A. lahorensis
      nymph-3 contained 5 protein fractions; O. papillipes had 2 fractions, and O.
      moubata had 3 fractions. Electrophoretic protein separation showed the equal
      number of protein fractions within one genus of ticks. At the larval stage, the
      tick homogenates were always found to have one protein fraction. The hemolymph of
      O. papillipes and O. moubata ticks displayed differences between the imago and
      nymph-3. A new biochemical marker was proposed to establish a species affinity.

PMID- 17436731
TI  - [Mosquito complex (Diptera, Culicidae) in a West Nile fever focus in the
      Volgograd region. I. Species diversity and relative abundance in different
      habitats].
AB  - Potential West Nile virus (WNV) vectors were assessed during 2003 and 2004 at the
      indoor and outdoor collection sites of Volgograd and surrounding rural areas. A
      total of 26 387 female mosquitoes comprising 16 species in 5 genera of the
      subfamily Culicinae and 4 species of the subfamily Anophelinae were collected.
      The seasonal abundance and the dominance structure greatly differed in the multi
      storied buildings, farms, and open habitats whereas the similarity of species
      diversity remained high throughout the season. In the porches of buildings, Aedes
      vexans (58%) and Cx. pipiens (37%) prevailed in early July (the beginning of a
      transmission period), Cx. pipiens (92%) was an absolute dominant species in
      August. The autogenous form of Cx. pipiens was most common in the flooded
      basement houses of the city's outskirts. The number of anautogenous females in
      the indoor collections increased by August. Only the anautogenous form of Cx.
      pipiens was sampled in the open rural and urban areas. The findings suggest that
      the attraction of potential vectors, including anautogenous Cx. pipiens, from the
      outdoor biotopes to the porches of apartment houses is one of the main reasons
      for the spread of the disease in the urban population.

PMID- 17436732
TI  - [Characterization of contacts of the population of Guinea with synanthropic
      rodents as Lassa fever virus carriers].
AB  - Questionnaire surveys made in 17 villages from 3 ecological zones of Guinea have
      provided evidence for the population's contact with synanthropic rodents as Lassa
      fever virus carriers. Over 100 rodents are quarterly captured in the houses of
      the traditional type in the villages located in the savanna woodland. Less than
      10 specimens are captured at the food warehouses. There are more than 100 rodents
      in the majority of houses of the traditional type in the villages located in the
      secondary forest. In the villages of rainy tropical forests, the capture rate is
      low--10 to 100 rodents. The main rodent capturers are boys and young men (aged 7
      to 20 years) who are principal rodent meat eaters; although almost the whole
      population, particularly in rural areas, consumes this meat in varying degrees.
      The proportion of captured rats of the genus Mastomys (the carrier of Lassa fever
      virus) in the town of Kindia is 11%. In the rural area, it is much higher (as
      high as 94%) in the villages located in the rainy tropical forests. It is
      estimated that one trapper quarterly catches 0.2 (in the savanna woodland) to 6.9
      (in the secondary forests) infected rats, which agrees with the data of a
      serological survey of Guinea's population. By and large, the majority of the
      Guinean population may be referred to as a group at risk for Lassa fever due to
      their permanent contacts with rodents.

PMID- 17436733
TI  - [Cryptosporidium infectiveness of aquatic mammals in the natural ecosystems of
      the Kursk Region].

PMID- 17436734
TI  - [Evaluation of the anticestodal activity of marnatol].

PMID- 17436735
TI  - [A case of concomitant hepatic lesion in a child with cystic hydatid disease and
      Arthropoda larva (nymph)].
AB  - A 15-year-old patient living in Bashkortostan was admitted as having a diagnosis
      of hydatid cyst of the left hepatic lobe for surgical treatment. He had the
      following concomitant diseases: neurodermatitis, bronchial asthma, and acute
      respiratory disease. After surgery (laparoscopic echinococcectomy), a portion was
      taken from the parent vesicle wall for a histological study. The parasite was
      detected on the inner membrane surface. It is suggested that this is a Pentastoma
      sp. (Arthropoda, Maxillopoda, Pentastomida, and Cephalobaenida). Thus, the
      observed patient has a combined hepatic invasion with Echinococcus and
      Pentastoma).

PMID- 17436736
TI  - [Cryptosporidiosis: current views of its pathogenesis and resistance].
AB  - Cryptosporidiosis is a socially dangerous opportunistic infection that is
      intractable and, according to recent data, caused by a diversity of species of
      the genus Cryptosporidium, which are still recently considered to be
      nonpathogenic to a human being. The transmission of this infection is by the
      water route and the technology of water purification cannot be saved from the
      oocysts of Cryptosporidium. Therefore, the important line of investigations is to
      study the immunological aspects of the interaction of Cryptosporidia with the
      cells of a microorganism, the development of a pathological process, and the
      persistence of the pathogen. The review analyzes the factors providing the
      mobility of the pathogen, its attachment to and penetration into the cell. The
      inhibitory effect of a number of substances preventing the binding of sporozoites
      to the cell is described. It has been established that Cryptosporidia can control
      the apoptosis of the host's cells and affect different other parameters of cell
      functional activity. It is shown that infection resistance depends on many
      factors and it is studied on models with genome or immunity or artificially
      induced defects. Nitric oxide should be emphasized among the determinants of
      natural resistance to Cryptosporidia. gamma-IFN has a dominant role in infection
      control and the good response to infection is associated with the production of a
      number of cytokines mainly of the Th1 type. There is evidence that there is a
      relationship of the local immune response to the systemic one in
      cryptosporidiosis. It is noted that the loss of local immune reactions may cause
      severe sequels in patients with immunodeficiencies. The importance of nonspecific
      T-cell defense and antiparasitic antibodies in the control of the infection is
      demonstrated. It is concluded that the studies that give a better insight into
      the systemic mechanisms of infection protection should be conducted. In this
      direction, it is promising to construct models of cryptosporidiosis in the
      immunocompetent host and those of generalized infection, which will assist in
      studying the mechanisms that are responsible for the control of cryptosporidial
      dissemination in immunodeficiencies.

PMID- 17436737
TI  - [Nikolai Nikolaevich Petrov (1876-1964)].

PMID- 17436738
TI  - [Single-stage operations for synchronous multiple primary and metastatic cancer
      of the lung and other organs].
AB  - The work presents an experience with the diagnosing of synchronous tumors of
      double localization in 256 patients. Operations were performed on 146 of them.
      Single-stage operations were made in 55 cases. When performing single-stage
      operations, 20 patients were found to have cancer of the lung with distant
      metastases or cancer of other localization with a metastasis in the lung. In the
      other 35 patients the diagnosis of true polyneoplasia was made followed by
      radical operations. Advantages of single-stage operations are shown, performing
      the first stage of the operation on the lung being substantiated. The five year
      survival after surgical treatment of multiple primary cancer was 15%.

PMID- 17436739
TI  - [The place of endovideosurgical interventions in treatment of inguinal hernias].
AB  - Endovideosurgical hernioplasty was performed in 3020 patients. Complex forms of
      inguinal hernias were diagnosed in 280 of them. These forms included: bilateral
      and combined inguinal hernias, inguinoscrotal hernias, sliding hernias, fixed and
      irreducible inguinal hernias, recurrent inguinal hernias after traditional
      herniorrhaphy and recurrent hernias after endovideosurgical hernioplasty.
      Original technical maneuvers are described, indications and contraindications
      were established, complications and results of treatment of patients with
      inguinal hernias were analyzed and evaluated. Recommendations are given for the
      treatment of patients with complex forms of hernias.

PMID- 17436740
TI  - [Experimental and clinical grounds of revascularizing osteomyoplasty for
      treatment of critical ischemia of the lower extremities].
AB  - In an experimental work it was found that under conditions of muscle ischemia the
      revascularizing osteomyoplasty was better than revascularizing osteotrepanation:
      it resulted in 1.4 times greater diameter of muscle fibers and 1.3 times larger
      size of the capillary network. An analysis of treatment of 30 patients was made
      who had critical ischemia of the extremities against the background of a diffuse
      lesion of the arteries below the inguinal ligament. In the first group consisting
      of 15 patients standard revascularizing osteotrepanation of the femur and shin
      was performed, in the second group (15 patients) revascularizing osteomyoplasty
      on the shin was added to the revascularizing osteotrepanation on the femur. In
      the second group the percentage of "mild improvement" of the clinical status of
      the patients was 10 times greater, and the number of patients with "minimal
      improvement" was 3.7 times less.

PMID- 17436741
TI  - [Syndrome of mutual aggravation of injuries in patients with a combined trauma].
AB  - An analysis of 1458 case histories of patients with a combined trauma has shown
      that 276 of the patients died, the lethality was 18.9%. The severity of each
      injury was estimated by the AIS scale, the severity of combined traumas--by the
      ISS scale. The syndrome of mutual aggravation of injuries manifested itself most
      brightly in the cases where one or more main injuries were dangerous for life. Of
      the greatest importance was an addition of the closed chest trauma to the
      dominating injury that resulted in a greater number of bronchial-pulmonary
      complications. Severe damages of the loco-motor system increased the number of
      thrombo- and fat embolism.

PMID- 17436742
TI  - [Specific features of the distribution of hydration and electrolyte ions in the
      brain structures in patients dead of severe cranio-cerebral trauma].
AB  - An analysis of hydration in the brain structures was made in 34 dead of severe
      cranio-cerebral traumas with hematomas, foci of crushing of different
      localization in patients who underwent open operations on the brain. An uneven
      (mosaic) distribution of water was revealed where the norm of hydration and
      dehydration occurred more often than hyperhydration in different structures of
      the brain.

PMID- 17436743
TI  - ["Splint dishabituation" in treatment of distal injuries of the digital extensor
      tendons].
AB  - Results of treatment of 61 patients with "mallet finger" injuries have been
      analyzed. After discontinuation of permanent immobilization the patients of the
      main group (n = 20) underwent "splint dishabituation" consequentially and bit by
      bit during 8 weeks, according to an original protocol developed with special
      reference to the stages of biological process of union of the damaged tendon.
      Following permanent immobilization patients of the group of comparison (n = 35)
      were recommended to use a removable splint at night during two weeks. The
      proposed protocol of "splint dishabituation" improved the results of treatment of
      injuries of the "mallet finger" type.

PMID- 17436744
TI  - [Substantiation of a reliable method of closing the bronchial stump in
      pneumonectomy].
AB  - The article is based on materials of investigation of the formation and healing
      of the bronchus stump in dogs, investigation of special structure of the main
      bronchi and related with it strength characteristics when using different methods
      of treatment of the bronchus stump and bronchial suture on tracheo-bronchial
      complexes. The postoperative course after pneumonectomy was analyzed in 530
      patients. A new method of treatment of the bronchus stump was proposed (a
      modified Overholt means) and closing the stump by compression from the outside by
      special clips. The method combines good strength, and positive features of a
      unified and individualized method of part-through, out-of-mucus suture of the
      bronchus.

PMID- 17436745
TI  - [A method of pylorus-preserving resection of the stomach for duodenum ulcer
      disease].
AB  - A method of pylorus-preserving resection of the stomach including dissection of
      the ulcer and segmental resection of the duodenum followed by a pylorus
      preserving resection of the stomach was developed and used in the clinic in 8
      patients with ulcer disease of the duodenum. Positive effect manifested itself as
      preserved functional activity of the pylorus complex and duodenum. The method
      allows securing adequate pathogenetic effects, leveling the development of such
      complications as chronic impairment of duodenal patency, duodenal-gastric reflux,
      dumping syndrome.

PMID- 17436747
TI  - [Metastasis of lung cancer into the diverticulum of the small intestine with its
      perforation].

PMID- 17436746
TI  - [Potential of endoscopic hemostasis in patients with gastroduodenal bleedings].
AB  - The authors have analyzed their experiences with treatment of 61 patients using
      the method of endoscopic clipping: 24 of them had the source of bleeding in
      chronic ulcers of the duodenal bulb, 6 had chronic gastric ulcers, 15 had acute
      gastric ulcers, 2 had acute ulcers of the duodenal bulb, Mallory-Weiss syndrome
      was found in 2 patients, Dieulafoy syndrome in 10 patients and one patient had
      peptic ulcer of the gastro-entero-anastomosis. The endoscopic clipping was made
      in 11 patients, in 31 patients injections of adrenaline and coagulation were
      added, in 9 patients--coagulation only, in 2 patients--irrigation with
      caproferon, in 8--adrenaline injections. In 57 out of 61 patients reliable
      hemostasis was achieved.

PMID- 17436748
TI  - [Foreign body in the small intestine].

PMID- 17436749
TI  - [Invasive methods of diagnosis of interstitial disease of the lungs].

PMID- 17436750
TI  - [Chronic and acute adrenal insufficiency in surgical practice].

PMID- 17436751
TI  - [Stenosing ligamentitis of fingers].

PMID- 17436752
TI  - [Mental ecology: from dependency disorders concept to systemic health
      monitoring].
AB  - The author deals with factors and conditions of dependency disorders development,
      specifies synergic concept of dependency behavior, defines fractals of
      psychogenesis, somatogenesis and sociogenesis of dependencies. The article covers
      definitions of mental health and mental ecology, conceptual and structural
      pattern of systemic ecologic monitoring including mental health monitoring.

PMID- 17436753
TI  - [On problem concerning palliative protective means against chemical exposure].
AB  - The article covers principles and methods of radical and palliative (auxillary)
      anti-chemical protection. The author presents personal materials on molecular
      (inherited and acquired) markers of increased individual sensitivity to ecotoxic
      materials, results of personal experiments on using antidote nutrition for
      preventing isocyanate and cadmium effects.

PMID- 17436754
TI  - [Relationship between microelements content of drinkable water and
      nephrolithiasis formation in Moscow region residents].
AB  - The article covers theoretical and practical matters on prevalence, incidence of
      nephrolithiasis in Moscow region and influencing ecological hazards. Predictive
      role of those matters is evaluated. The author presented features of drinkable
      water in Moscow region and revealed changes in nephrolithiasis prevalence in
      accordance with antropogenous load. Correlation between the nephrolithiasis
      prevalence and the microelements ratio in drinkable water is established.

PMID- 17436755
TI  - [Myocardial infarction at the age under 50: influence of occupational xenobiotics
      (analysis of chemical elements in hair of patients)].
AB  - X-ray and fluorescence analysis covered elemental composition of hair in 39
      patients with myocardial infarction and 23 healthy individuals. The highest
      "chemical pollution" was seen in myocardial infarction patients whose occupations
      are associated with xenobiotics exposure. Hair of those patients contain reliably
      high amounts of iron, copper, manganese, chromium, cadmium, lead, strontium,
      rubidium, potassium, bromium and clorine. Nearly two thirds of those patients had
      potassium and strontium levels considerably exceeding maximally allowable values.
      Reliably higher levels of some chemical elements in myocardial infarction
      patients vs. controls could be a proof of direct cause-effect relationships
      between xenobiotics influence and coronary affection in individuals aged under
      50, especially subjected to regular risk factors.

PMID- 17436756
TI  - [Contemporary views of role played by neuro-humoral and adenylate cyclase systems
      in occupational allergic skin diseases (review of literature)].

PMID- 17436757
TI  - [Parameters of lipid metabolism as criterion of chemical jeopardy].
AB  - The author studied parameters characterizing lipid metabolism in experimental
      animals (white rats) varying in age, revealed relationships between lipid
      metabolism and the age, demonstrated information value of some lipid metabolism
      parameters for studying chemicals accelerating natural gerontogenesis.

PMID- 17436758
TI  - [Complex technology of waste demercuration solutions purifying from mercury].
AB  - The authors studied sorption of mercurial anion complexes on AN-31 ion exchangers
      in J(-) form and AV-17 industrial ion exchanger containing groups of quarternary
      ammonium base, in J(-)3 form. Findings are that putting an oxidizer (polyiodide)
      into sorbent improves purification degree of mercury-containing solutions up to
      MAC. The authors suggested a technologic scheme to purify waste demercuration
      solutions for practical use.

PMID- 17436759
TI  - [Forecasting toxicometry parameters in phenol derivatives on basis of "chemical
      structure--biologic activity" principle].

PMID- 17436760
TI  - [Studying prevalence of muscle-skeletal system and connective tissue among adult
      rural population of Lipetsk region].

PMID- 17436761
TI  - [Health of children born by mothers dwelling in areas with variable technogenic
      load].

PMID- 17436762
TI  - Information about tuberculin skin test (TST) conversion rates for the US Navy and
      Marine Corps.

PMID- 17436763
TI  - Anesthesia services during operation unified assistance, aboard the USNS Mercy,
      after the tsunami in Southeast Asia.
AB  - The tsunami that struck Southeast Asia on December 26, 2004, resulted in the
      deaths of >300,000 individuals. The U.S. response included the formation of the
      first combined civilian/ military peacetime humanitarian effort, directed by the
      National Command Authority as Operation Unified Assistance. This effort included
      military personnel from the U.S. Navy and civilians assembled by Project HOPE.
      Anesthesiologists and certified nurse anesthetists provided care in >150 cases.
      We discuss the initial response, medical and cultural planning, logistical
      support, procedures, and lessons learned in this unique opportunity.

PMID- 17436764
TI  - Creating order from chaos: part I: triage, initial care, and tactical
      considerations in mass casualty and disaster response.
AB  - How do we train for the entire spectrum of potential emergency and crisis
      scenarios? Will we suddenly face large numbers of combat casualties, an
      earthquake, a plane crash, an industrial explosion, or a terrorist bombing? The
      daily routine can suddenly be complicated by large numbers of patients, exceeding
      the ability to treat in a routine fashion. Disaster events can result in patients
      with penetrating wounds, burns, blast injuries, chemical contamination, or all of
      these at once. Some events may disrupt infrastructure or result in loss of
      essential equipment or key personnel. The chaos of a catastrophic event impedes
      decision-making and effective treatment of patients. Disasters require a paradigm
      shift from the application of unlimited resources for the greatest good of each
      individual patient to the allocation of care, with limited resources, for the
      greatest good for the greatest number of patients. Training and preparation are
      essential to remain effective during crises and major catastrophic events.
      Disaster triage and crisis management represent a tactical art that incorporates
      clinical skills, didactic information, communication ability, leadership, and
      decision-making. Planning, rehearsing, and exercising various scenarios encourage
      the flexibility, adaptability, and innovation required in disaster settings.
      These skills can bring order to the chaos of overwhelming disaster events.

PMID- 17436765
TI  - Creating order from chaos: part II: tactical planning for mass casualty and
      disaster response at definitive care facilities.
AB  - Current events highlight the need for disaster preparedness. We have seen
      tsunamis, hurricanes, terrorism, and combat in the news every night. There are
      many variables in a disaster, such as damage to facilities, loss of critical
      staff members, and overwhelming numbers of casualties. Each medical treatment
      facility should have a plan for everything from caring for staff members to
      getting the laundry done and providing enhanced security or mortuary services.
      Communication and agreements with local, regional, and federal agencies are
      vital. Then we must train and drill to shape the tools to impose order on chaos
      and to provide the most care to the greatest number.

PMID- 17436766
TI  - Cost drivers and resource allocation in military health care systems.
AB  - This study illustrates the feasibility of incorporating technical efficiency
      considerations in the funding of military hospitals and identifies the primary
      drivers for hospital costs. Secondary data collected for 24 U.S.-based Army
      hospitals and medical centers for the years 2001 to 2003 are the basis for this
      analysis. Technical efficiency was measured by using data envelopment analysis;
      subsequently, efficiency estimates were included in logarithmic-linear cost
      models that specified cost as a function of volume, complexity, efficiency, time,
      and facility type. These logarithmic-linear models were compared against
      stochastic frontier analysis models. A parsimonious, three-variable, logarithmic
      linear model composed of volume, complexity, and efficiency variables exhibited a
      strong linear relationship with observed costs (R(2) = 0.98). This model also
      proved reliable in forecasting (R(2) = 0.96). Based on our analysis, as much as
      $120 million might be reallocated to improve the United States-based Army
      hospital performance evaluated in this study.

PMID- 17436767
TI  - Ensuring respect for persons when recruiting junior enlisted personnel for
      research.
AB  - Junior enlisted personnel in the Navy at training commands or recruit depots who
      are recruited for research can be considered a "captive audience" and therefore
      require special precautions to ensure that the ethical principle of respect for
      persons is maintained. Unfortunately, this can be difficult because of the
      hierarchical structure of the military and closed communities of junior enlisted
      personnel at training commands and recruit depots. This article provides a
      theoretical discussion of the ethical issue of autonomy and the essential
      elements of informed consent that Navy researchers need to address when
      recruiting subjects from this population. Two relevant policy statements to Navy
      researchers, Department of Defense Directive 3216.2 and Bureau of Medicine and
      Surgery Instruction 3900.6B, which provide guidance for protection of human
      subjects, are reviewed and critiqued, and a suggested plan to ensure the ethical
      principle of respect for persons is presented.

PMID- 17436768
TI  - Premilitary sexual assault and attrition in the U.S. Navy.
AB  - A prospective study examined whether adult premilitary sexual victimization
      predicted women's military attrition. In a survey of female Navy recruits (N =
      2,431), 56% reported some form of adult unwanted sexual contact before entering
      the military, with 25% reporting completed rape. Approximately one-third of
      respondents left the Navy before completing their 4-year term of service. When
      rape, attempted rape, and lower-level unwanted sexual contact were considered
      simultaneously, only rape predicted attrition. Women who reported premilitary
      rape, compared with those who did not, were 1.69 times more likely to leave the
      military. The pattern of results held across the 4-year period examined and after
      controlling for demographic predictors.

PMID- 17436769
TI  - Military sexual trauma: violence and sexual abuse.
AB  - Military sexual trauma includes sexual assault and sexual harassment in military
      settings by intimate partners and active duty personnel. Such violence triggers a
      syndrome of episodic, clustered, psychological and physiological symptoms that
      may be fatal. Despite its pervasiveness, many clinicians fail to recognize as
      many as 95% of cases among veterans and active duty personnel. Many victims
      receive inadequate medical treatment or education. They face a decreased quality
      of life, high morbidity and mortality rates, and economic losses. Their children
      may also be at risk for abuse. In many settings, clinicians may not realize the
      high prevalence of this military sexual abuse among veterans and active duty
      personnel. Clinicians should understand the clinical manifestations, to detect
      abuse early, to treat it appropriately, and to minimize sequelae.

PMID- 17436770
TI  - Cohesion, burnout, and past trauma in tri-service medical and support personnel.
AB  - Past research suggests that the negative consequences related to exposure to
      traumatic events and injury may impact cohesive work relationships. Additionally,
      trauma and low cohesive relationships independently predict poorer psychological
      and physical health in service members. The objective of the present study was to
      examine the interrelationships between exposure to traumatic events, burnout, and
      cohesion among tri-service medical and support staff. Surveys were administered
      to 253 U.S. Army, Army Reserve Units, U.S. Air Force, and U.S. Navy personnel
      upon arrival in Hawaii for participation in a stressful, 2-week training
      exercise. Results showed that history of trauma was correlated with poorer view
      of officers and higher levels on two components of burnout. We discuss how
      findings can apply to prevention and early intervention efforts.

PMID- 17436771
TI  - Psychotic symptoms in combat-related post-traumatic stress disorder.
AB  - The presence of psychotic symptoms in post-traumatic stress disorder (PTSD) has
      already been recognized. Using the Structured Clinical Interview Diagnostic and
      Statistical Manual, we searched for and assessed psychotic symptoms in 91 males
      suffering from combat-related PTSD. Hallucinations and delusions were present in
      20% of patients. We divided all patients into three groups: the group with
      hallucinations and delusions, the group without these symptoms, and the group
      with "subthreshold" psychotic symptoms. Using the Harvard Trauma Questionnaire,
      Clinician-Administered PTSD Scale, and Structured Clinical Interview Diagnostic
      and Statistical Manual, we investigated differences between groups in the
      intensity of traumatization, severity of PTSD symptoms, and the frequency of
      depression. There were no significant differences between groups; however, there
      was one exception: severity of hyperarousal symptoms was positively correlated
      with occurrence of psychotic symptoms.

PMID- 17436772
TI  - Suicide rate among former Swedish peacekeeping personnel.
AB  - Increased suicide rates for military personnel suffering from post-traumatic
      stress disorders have been reported in various countries. Although it is known
      that some peacekeepers are exposed to potentially traumatic events and are thus
      at risk of suffering from post-traumatic stress reactions, only a few studies
      have examined suicide rates in this group. Therefore, the aim of this study was
      to investigate the suicide rate among former Swedish peacekeeping personnel. We
      compared 39,768 former Swedish peacekeepers to the general population in the
      National General Population Registry and the Cause-of-Death Registry. A lower
      number of suicides was found among former Swedish peacekeepers than in the
      general population. In conclusion, Swedish personnel serving in international
      peace-keeping operations do not show a higher suicide rate than the general
      population. Unique problems associated with this research area are discussed.

PMID- 17436773
TI  - Sociodemographic profile of women entering a military substance use disorder
      treatment center.
AB  - This retrospective study reviewed medical records to determine sociodemographic
      characteristics of women in a substance use treatment center at a Pacific
      Regional Medical Command facility. Data were collected from records between
      September 1, 1999, and August 31, 2002. Three questions were investigated, as
      follows. (1) What are the sociodemographic characteristics of women entering
      substance abuse treatment? (2) Are there coexisting conditions (psychiatric
      history and/or family history of abuse or psychiatric conditions) that accompany
      the substance abuse problem? (3) What are the referral sources for patients
      entering treatment? Data were analyzed by using descriptive statistics. The
      sample was primarily Caucasian, between 18 and 25 years of age. The most
      frequently occurring conditions were depression and anxiety. The smallest number
      of referrals was from primary care managers. The findings support the need for
      thorough screening and assessment for substance use in women and assessment of
      primary care managers' compliance, knowledge, and skills in evaluating substance
      use in women.

PMID- 17436774
TI  - Cigarette use among two cohorts of U.S. Air Force recruits, compared with secular
      trends.
AB  - This study provides a comparison of cigarette smoking among two cohorts of U.S.
      Air Force recruits. The first cohort, Air Force 1, entered the military between
      August 1995 and August 1996. The second cohort, Air Force 2, entered between
      October 1999 and September 2000. Cigarette use significantly increased among both
      men (7.0-percentage point increase) and women (7.3-percentage point increase)
      between the two cohorts. This difference remained statistically significant in
      models adjusted for demographic differences between the two groups of recruits.
      Direct standardization methods were then used to compare rates in both Air Force
      surveys with rates of current smoking reported for a national sample from the
      Behavioral Risk Factor Surveillance System surveys from the same years. Although
      the average number of cigarettes smoked and years of smoking decreased between
      the two cohorts, troops from Air Force 2 reported being less motivated to quit.
      This study suggests that efforts to reduce smoking among junior enlisted troops
      in the Air Force should be bolstered.

PMID- 17436775
TI  - Protective ventilation strategies in the management of phosgene-induced acute
      lung injury.
AB  - Phosgene is a chemical widely used in the plastics industry and has been used in
      warfare. It produces a life-threatening pulmonary edema within hours of exposure,
      to which no specific antidote exists. This study aims to examine the
      pathophysiological changes seen with low tidal volume ventilation (protective
      ventilation (PV)) strategies compared to conventional ventilation (CV), in a
      model of phosgene-induced acute lung injury. Anesthetized pigs were instrumented
      and exposed to phosgene (concentration x time (Ct), 2,350 mg x min x m(-3)) and
      then ventilated with intermittent positive pressure ventilation (tidal volume
      (TV) = 10 ml x kg(-1); positive end expiratory pressure, 3 cm H2O; frequency, 20
      breaths x min(-1); fractional concentration of inspired oxygen, 0.24), monitored
      for 6 hours after exposure, and then randomized into treatment groups: CV, PV (A)
      or (B) (TV, 8 or 6 ml x kg(-1); positive end expiratory pressure, 8 cm H2O;
      frequency, 20 or 25 breaths x min(-1); fractional concentration of inspired
      oxygen, 0.4). Pathophysiological parameters were measured for up to 24 hours. The
      results show that PV resulted in improved oxygenation, decreased shunt fraction,
      and mortality, with all animals surviving to 24 hours compared to only three of
      the CV animals. Microscopy confirmed reduced hemorrhage, neutrophilic
      infiltration, and intra-alveolar edema.

PMID- 17436776
TI  - Physician versus paramedic in the setting of ground forces operations: are they
      interchangeable?
AB  - BACKGROUND: The setting of military ground force operations can be demanding and
      requires a matched medical assistance plan. A major consideration is the type of
      medical caregiver that is assigned to the mission. We studied the similarities,
      differences, advantages, and disadvantages of physicians versus paramedics in
      this scenario. METHODS: We interviewed 20 ground force physicians, highly
      experienced in this setting. We summarized their responses and formulated
      quantitative decision-making tables regarding two sorts of missions: a long
      duration mission, far from friendly definitive care, and a short-duration
      mission, close to friendly hospitals. RESULTS: The major areas in which
      physicians and paramedics differ, pertinent to a ground force operation are:
      formal education, on-job training, knowledge base, ability to treat a wide
      variety of medical conditions, ability to perform manual lifesaving procedures,
      social and moral impact, availability, physical fitness, combat skills, and cost.
      Of a maximum score of 100 points, for a long-term mission a physician scores 77.7
      points while a paramedic scores 63.6 points. The scores for a short-term mission
      are 72.7 and 67.9, respectively. DISCUSSION: Physicians and paramedics are
      distinct groups of medical caregivers and this is also true for the setting of
      ground force operations. They are not interchangeable. Our data show that a
      physician has a relative advantage over a paramedic, especially in long-term
      missions, far from friendly facilities. CONCLUSION: A physician is the first
      choice for all kinds of military ground force missions while a paramedic can be a
      reasonable substitute for missions of short duration, close to definitive care.

PMID- 17436777
TI  - Initial subjective load carriage injury data collected with interviews and
      questionnaires.
AB  - This study aimed to identify the types, incidence, and causes of any potential
      load carriage injuries or discomfort as a result of a 2-hour, forced-speed,
      treadmill march carrying 20 kg. Subjective load carriage data were collected,
      through both interviews and questionnaires, from relatively inexperienced
      soldiers after a period of load carriage. Results from the study showed that the
      upper limb is very susceptible to short-term discomfort, whereas the lower limb
      is not. The shoulders were rated significantly more uncomfortable then any other
      region, and blisters were experienced by approximately 60% of participants.
      Shoulder discomfort commences almost as soon as the load is added and increases
      steadily with time; however, foot discomfort increases more rapidly once the
      discomfort materializes. In conclusion, early development of shoulder pain or
      blisters may be a risk factor for severe pain or noncompletion of a period of
      prolonged load carriage.

PMID- 17436778
TI  - The effect and safety of short-term creatine supplementation on performance of
      push-ups.
AB  - The effects of short-term oral creatine (Cr) supplementation on exercise
      performance and on blood pressure and renal function were assessed. Thirty-five
      healthy, active duty, U.S. Army volunteers (20 men and 15 women; age, 22-36
      years) at Fort Sam Houston, Texas, supplemented their diet for 7 days with 20
      g/day of either Cr or taurine (as placebo). There was no significant difference
      in 2-minute push-up counts between the Cr and taurine groups from before to after
      supplementation (p = 0.437; power = 0.98). The Cr group demonstrated a
      significant increase in serum creatinine levels (p < 0.001), compared with the
      taurine group, and this increase could be misinterpreted as impairment of renal
      function. No adverse changes in blood pressure, body composition, weight, or
      serum Cr phosphokinase levels were observed. We conclude that short-term Cr
      supplementation appears to be safe but does not enhance push-up performance.

PMID- 17436779
TI  - Effect of reactive skin decontamination lotion on skin wound healing in
      laboratory rats.
AB  - Reactive skin decontamination lotion (RSDL) is a proposed replacement for the
      existing skin and equipment decontamination kit. Because RSDL may need to be used
      to decontaminate wounded personnel, we conducted an assessment of the effect of
      this agent on wound healing. A skin incision model using male Sprague Dawley rats
      (n = 19 rats/group) was used. A 7.0-cm incision was made through the skin, and
      RSDL was (experimental group) or was not (control group) applied to the open
      wound; the wound edges were then approximated with sutures. Seven days later,
      animals were euthanized and wound samples were taken. Healing was assessed by
      measuring mechanical strength, collagen content, and histological appearance.
      RSDL-treated wounds had 23% lower tensile strength (p < 0.05) and 11% lower
      collagen content (p < 0.05) than did the untreated control wounds. Histological
      assessments did not differ significantly between groups. The results of this
      investigation demonstrate that the application of RSDL directly to an open wound
      impairs wound strength and decreases collagen content in the early phases of
      wound healing. This may have clinical implications for the treatment and outcomes
      of chemical casualty combat trauma.

PMID- 17436780
TI  - Comparison of three strategies for preventing hypothermia in critically injured
      casualties during aeromedical evacuation.
AB  - Critically injured patients are at risk for hypothermia. This study determined
      the efficacy of three hypothermia prevention strategies: the ChillBuster warming
      blanket, ChillBuster with a reflective blanket, and two wool blankets. A quasi
      experimental design was used to compare changes in core temperature. Following
      resuscitation from hypovolemic shock, 20 swine were assigned to one of the three
      interventions, placed in an environmental chamber set to reproduce in-flight
      conditions onboard a military cargo aircraft (50 degrees F/airspeed 0.2 m/s), and
      monitored for 6 hours. A repeated measures analysis of variance and least-squared
      difference post hoc were performed. The ChillBuster/reflective blanket group was
      significantly warmer than the ChillBuster only group and the wool blanket group
      (p < 0.01). After 6 hours of cold exposure, the ChillBuster/reflective blanket
      group remained warm while the ChillBuster only and wool blanket groups developed
      mild hypothermia. Combined use of a warming blanket and reflective blanket was
      effective in preventing hypothermia over 6 hours and is feasible in a deployed
      military environment.

PMID- 17436781
TI  - Perforation of the colon from the primary blast effect of an extraperitoneal
      shotgun injury: case report.
AB  - Blast trauma can result in injuries to peritoneal organs. Penetrating
      extraperitoneal shotgun wounds and even tangential gunshot or shotgun injuries of
      the abdominal or chest wall can result in damage to abdominal organs despite an
      intact peritoneum and diaphragm. Delays in diagnosis and operative repair of such
      bowel injuries are frequently associated with high morbidity and mortality rates.
      We present a case of a 47-year-old man with a history of depression and a self
      inflicted shot-gun wound to the chest wall, which was tangential and never
      entered the chest cavity. Computed tomography of the chest revealed free
      subdiaphragmatic air. Exploratory laparotomy revealed a 4-cm perforation of the
      wall of the splenic flexure of the large bowel. There was no injury to the
      peritoneum, diaphragm, or other abdominal viscera. The colonic perforation was
      repaired by suturing with a stapling instrument. The operation was completed with
      an appendectomy and cecostomy.

PMID- 17436782
TI  - Deployable, field-sustainable, reverse transcription-polymerase chain reaction
      assays for rapid screening and serotype identification of dengue virus in
      mosquitoes.
AB  - Dengue virus universal and serotype 1 to 4 fluorogenic probe hydrolysis, reverse
      transcription (RT)-polymerase chain reaction (PCR) assays and positive-control
      RNA template were freeze-dried in a thermally stable, hydrolytic enzyme-resistant
      format and deployed for testing in a dengue fever-endemic region of Thailand. The
      study site presented austere testing conditions. Field-collected Aedes aegypti
      mosquitoes spiked with inoculated A. aegypti mosquitoes and individual and
      pooled, field-collected, A. aegypti, A. albopictus, and Culex tritaeniorhynchus
      mosquitoes were used for RT-PCR assay evaluations. For dengue virus-inoculated A.
      aegypti mosquitoes and spiked samples, in vitro sensitivity and specificity
      results for all five assays were concordant with indirect fluorescent antibody
      assay results. A single pool of field-collected, female, A. aegypti mosquitoes
      was identified as dengue virus positive. Cross-reactivity was not observed across
      heterologous serotypes, mosquito vectors, or human DNA. The limit of detection
      was >7 to < or =70 genomic equivalents. Sample processing and analysis required
      <2 hours. These results show promise of field-formatted RT-PCR reagents for
      rapid, sensitive, specific dengue virus screening and serotype identification in
      mosquitoes under field-deployed conditions.

PMID- 17436783
TI  - Vertebromedullary wound with ureteral fistula.
AB  - We report a case of associated vertebromedullary and ureteral lesions in a
      severely injured patient, a victim of a gunshot aggression in Africa. Urine
      extended from the ureteral fistula through the third lumbar vertebral body,
      blended with cerebrospinal fluid from the dural attrition, and flowed very slowly
      through the dorsal exit ballistic hole. This is to our knowledge the first such
      case described in the literature. Uro-computed tomography scan finally made the
      diagnosis of ureteral fistula after two neurosurgical procedures determined that
      initially presumed dural persistent fistula needed to be closed.

PMID- 17436784
TI  - Radiology corner. Answer to last month's radiology case and image (case #10):
      echinococcosis of the liver.

PMID- 17436785
TI  - Preop briefings gain momentum as a strategy for patient safety.

PMID- 17436786
TI  - Spinal fusion under the microscope.

PMID- 17436787
TI  - Six practices of the lean operating room.

PMID- 17436788
TI  - Practicing 'wasteology' in the OR.

PMID- 17436789
TI  - 5S: a lean method to cut the clutter.

PMID- 17436790
TI  - Are you up to speed on flash sterilization?

PMID- 17436792
TI  - Getting patients home quickly--and safely.

PMID- 17436791
TI  - Assessing patient risks from sleep apnea.

PMID- 17436793
TI  - [Controlled randomized studies do not always confirm the results suggested by
      observational studies].

PMID- 17436794
TI  - [Hyperkalemia].
AB  - Hyperkalemia is a frequently met electrolytic disorder in clinical practice.
      Blood potassium concentration is primarily under the control of cellular
      transfer, driven either by the acid basic equilibrium, the action of
      catecholamines and insulin, and secondarily by the kidney. In the majority of
      cases, hyperkaliemia is due to renal failure, together with the effect of drugs.
      The clinical symptoms, particularly cardiac manifestations, of hyperkaliemia can
      be serious, and this is why the identification of its cause and its treatment are
      of the utmost importance. The diagnostic strategy rests on a detailed history
      taking, centered on the drug therapies. The transtubular gradient of potassium
      can be useful, when there is a suspicion of hypoaldosteronism.

PMID- 17436795
TI  - [Hypokalemia: diagnosis and treatment].
AB  - Potassium disorders are the most common electrolyte abnormality in clinical
      practice. Hypokalemia is usually well tolerated in otherwise healthy people, but
      it can be life threatening when severe. Even mild or moderate hypokalemia
      increases mortality and morbidity in patients with cardiovascular disease.
      Hypokalemia is the result of an abrupt shift of potassium from the extra-cellular
      compartment into cells or more frequently the result of potassium depletion by
      abnormal losses (digestive or kidney). Medication (diuretics) is the most common
      cause of hypokalemia. In some cases the diagnosis is not readily apparent. In
      this setting, measurement of an urinary potassium excretion and assessment of
      acid-base balance are often helpful. When hypokalemia is identified, the disorder
      should be treated by treating the underlying cause.

PMID- 17436796
TI  - [Previous and new concepts in the management of symptomatic hyponatraemia].
AB  - Hyponatraemia is an electrolytic disorder whose danger is often underestimated.
      The treatment of symptomatic hyponatraemia has been a subject of controversy for
      a long time. This disorder needs to be treated aggressively and cautiously
      because of the associated risk of definitive neurological lesions. Recently, a
      number growing of studies recognised the high incidence of a concurrent condition
      that has to be diagnosed and treated: hypoxia.

PMID- 17436797
TI  - [Pregnancy in patients with underlying renal disease].
AB  - Pregnancy has generally been regarded as very high risk in women with chronic
      renal insufficiency. In this review, we describe the physiologic changes in
      systemic and renal haemodynamics during pregnancy, as well as the nature and
      severity of possible maternal and foetal complications in the setting of
      underlying renal disease. The risks are proportional to the degree of functional
      renal impairment, the presence or not of proteinuria and/or arterial hypertension
      at the time of conception, and are related to the type of underlying nephropathy
      or systemic disease in the mother. Furthermore, if the renal disease has been
      diagnosed before pregnancy, a better planning of the moment of conception, as
      well as a tight follow-up, allow for a better maternal and obstetrical outcome.

PMID- 17436798
TI  - [Chronic kidney disease and antidiabetic treatment].
AB  - Diabetic nephropathy is the leading cause of chronic renal failure (CRF) in
      Europe. About fifty percent of diabetic subjects develop microalbuminuria, which
      progresses towards established diabetic nephropathy in one third of patients. The
      treatment of type 2 diabetes in a patient with CRF is a challenge for the general
      practitioner, because of the accumulation of drugs and/or specific metabolites.
      Sulfonylureas are associated with an increased risk of hypoglycaemia. Biguanides
      may exceptionally cause life-threatening lactic acidosis. Glitazones have an
      interesting profile since they decrease microalbuminuria and blood pressure.
      However, their safety is not well defined in the context of CRF In the case of
      severe CRF, only insulin and repaglinide can be recommended.

PMID- 17436799
TI  - [Magnesium metabolism disturbances].
AB  - Magnesium metabolism disturbances Magnesium (Mg) is the second most abundant
      intracellular cation. Only 1% of Mg is in the extracellular fluid and the plasma
      Mg concentration does not reflect a substantial tissue depletion. Hypomagnesemia
      is the most common abnormality of Mg balance. This disorder is often associated
      with hypocalcemia, hypokalemia and metabolic alkalosis. Hypomagnesemia must be
      suspected in any patient with alcoholism, chronic diarrhoea or on diuretic. The
      24-hour urinary Mg excretion of greater than 10 to 30 mg (1 mmol) or a calculated
      fractional excretion of Mg of greater than 2% suggest inappropriate renal
      wasting. Symptomatic hypomagnesemia must be treated by intravenous Mg, following
      by oral intake of Mg salt and by Mg rich diet. Hypermagnesemia is rare and occurs
      in case of high load and/or when renal function is impaired.

PMID- 17436800
TI  - [Renal metabolic acidosis: physiopathology, diagnosis and treatment].
AB  - Metabolic acidosis is not uncommon in clinical medicine. The kidney plays a
      pivotal role to maintain acid-base homeostasis. Understanding renal acid-base
      metabolism is essential to make an effective approach to the diagnosis and
      management of metabolic acidosis. Clinical approach includes the serum anion gap
      which allows to classify metabolic acidosis as increased anion gap or non-anion
      gap acidosis. Renal tubular acidosis refers to a group of functional disorders
      which differ depending on the localisation of the tubular defect. The management
      of metabolic acidosis is discussed according to the causes. The indications to
      use sodium bicarbonate are discussed as well as its potential adverse effects in
      some conditions.

PMID- 17436801
TI  - [Spondylodiscitis complicated by psoas abscess].

PMID- 17436802
TI  - [How to get rid of a patient?].

PMID- 17436803
TI  - [A single health insurance fund...].

PMID- 17436804
TI  - [There are sponsors and sponsors].

PMID- 17436805
TI  - [On France and neo-eugenics (4)].

PMID- 17436806
TI  - [Again in the front line: "cord blood banks"].

PMID- 17436807
TI  - [AIDS and circumcision: tragic impasses].

PMID- 17436808
TI  - [Geneva gets its first high security diagnostic laboratory in Switzerland].

PMID- 17436809
TI  - [Tolerance].

PMID- 17436810
TI  - [Sensitivity to various antibiotics of coagulase-negative staphylococci isolated
      from samples of milk from Dutch dairy cattle].
AB  - During recent years the prevalence of coagulase-negative staphylococci in milk
      samples from Dutch dairy cows has increased. In 1999 16.2% of the bacteria
      isolated from milk collected from cows with subclinical mastitis were coagulase
      negative staphylococci. In 2004 this proportion was 42.2%. The proportion of
      coagulase-negative staphylococci of the bacteria isolated from milk samples from
      cows with clinical mastitis was 7.3% in 1999 and 14.1% in 2004. In this study,
      the susceptibility of 108 coagulase-negative staphylococci to oxacillin,
      cefquinome, streptomycin, neomycin, penicillin, and the combination of nafcillin,
      penicillin, and streptomycin was tested. The isolates were cultured from milk
      collected from cows with mastitis and typed using the Api-Staph system. Eight
      species were identified. Staphylococcus chromogenes was the predominant species
      (41.7%), followed by Staphylococcus xylosus (15.7%) and Staphylococcus simulans
      (10.2%). With the agar dilution method all strains proved to be sensitive to
      cefquinome and 90% to oxacillin. Three isolates (2.8%) were mecA-positive.
      Despite the agar dilution results, these three isolates should be considered
      resistant to all beta-lactam antibiotics (penicillins, penicillins combined with
      a beta-lactamase inhibitor and all generations of cephalosporins). In the agar
      diffusion test, all isolates proved to be sensitive to the combination of
      nafcillin-penicillin-streptomycin, 99% were sensitive to neomycin and 1%
      intermediate sensitive, and 95% were sensitive to streptomycin, 4% resistant, and
      1% intermediate sensitive. The coagulase-negative staphylococci were highly
      resistant to penicillin (37.4%), although the level of resistance varied between
      species, from 0% for Staphylococcus simulans to 100% for Staphylococcus
      saprophyticus. Because coagulase-negative staphylococci are resistant to several
      antibiotics, sensitivity testing is important for targeted treatment of mastitis.

PMID- 17436811
TI  - [Clinical and experimental studies of osteogenesis in dogs].

PMID- 17436812
TI  - [Messing with sugar--the two cats].

PMID- 17436813
TI  - [Tail amputation in sheep, decision making with a tail?].

PMID- 17436814
TI  - [Veterinary drugs in horses. The law and its meaning of the positive list].

PMID- 17436815
TI  - [Yearly report 'Committee Promotion Veterinary Products'].

PMID- 17436816
TI  - [How veterinarians learn their entire life].

PMID- 17436817
TI  - [Wild animals and public health. Also important in the Netherlands].

PMID- 17436818
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, et cetera. Pedigree registration].

PMID- 17436819
TI  - ['The importance of the recognizing the importance constantly increases'.
      Organizational meeting animal welfare].

PMID- 17436820
TI  - Preventing vascular events in high-risk patients: primary care on the front line.

PMID- 17436821
TI  - The patient with cardiovascular disease: treatment strategies for preventing
      major events.
AB  - An abundance of clinical data exists to support the ability of pharmacologic
      interventions to reduce risk for vascular events significantly; however, there
      remains a gap between this evidence and current clinical practice. Recent data
      from large-scale, placebo-controlled statin trials demonstrate that these agents
      dramatically reduce risk for cardiovascular events, even in moderate-risk
      patients with normal to moderately elevated cholesterol levels. Data from trials
      of a broad range of antihypertensives reinforce the value of blood pressure (BP)
      management and indicate that some of these agents may have additional benefits
      beyond BP reduction. Similarly, meta-analyses of randomized trials confirm that
      antiplatelet therapy prevents serious cardiovascular events in a wide range of
      high-risk patients. Each of these interventions alone has been demonstrated to
      reduce the risk for vascular events by approximately 25 to 30%. A combination
      approach utilizing intensive risk-reducing therapy with more than one of these
      agents has the potential to reduce the risk for vascular events by as much as
      75%. Combined with nonpharmacologic risk reduction strategies, including
      exercise, diet, and smoking cessation, an opportunity exists to reduce the
      incidence of both first and recurrent cardiovascular events dramatically.

PMID- 17436822
TI  - The patient with diabetes: preventing cardiovascular complications.
AB  - In the United States, 18 million adults have diabetes and an additional 16
      million have impaired glucose tolerance. Of these patients, 75% will die of some
      form of heart or vascular disease. Furthermore, recent data suggest that even
      prediabetic patients are at increased risk for cardiovascular (CV) events.
      Patients with diabetes often have multiple comorbid CV risk factors (e.g.,
      dyslipidemia, hypertension, hyperglycemia) that synergistically interact to
      accelerate the pathogenesis of CV disease and dramatically increase the risk for
      CV events. For example, compared with patients without diabetes, patients with
      diabetes have a 3- to 5-fold increased risk of death due to congestive heart
      disease at every cholesterol level and are at increased risk for hypertension and
      hypertension-related CV events. Patients with diabetes are likely to benefit from
      intensive therapy incorporating multiple CV risk-reduction strategies. Lipid
      modification--primarily reducing levels of low-density lipoprotein cholesterol
      (LDL-C) and triglycerides and increasing high-density lipoprotein cholesterol
      (HDL-C) through pharmacologic and lifestyle intervention--is an integral part of
      such therapy. Patients with diabetes will also benefit from intensive blood
      pressure-lowering therapy with multiple classes of antihypertensives including
      angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in
      particular, as well as concomitant antiplatelet therapy. An intensive risk
      reduction approach combining these treatments would dramatically reduce the
      incidence of CV morbidity and mortality in this high-risk patient population.

PMID- 17436823
TI  - Strategies for primary and secondary stroke prevention.
AB  - Of the 55 million deaths that occur annually, 1 in 10 is attributable to stroke.
      As a consequence, cerebrovascular disease is the second leading cause of death
      worldwide, and stroke is among the most devastating consequences of vascular
      disease, causing long-term disability and incurring high personal, societal, and
      financial costs. However, stroke is a highly preventable disease in the majority
      of patients. The goal of stroke prevention strategies is to identify high-risk
      patients through the presence of modifiable and nonmodifiable risk factors and to
      target these modifiable risk factors through the use of appropriate pharmacologic
      and nonpharmacologic interventions. Clinical and epidemiologic studies point
      toward three major risk-reducing pharmacologic therapies that together may
      dramatically reduce stroke risk. First, landmark clinical trials have
      demonstrated that the reduction of blood pressure in persons at risk for
      cerebrovascular disease significantly reduces stroke risk. Second, ample evidence
      supports the use of antiplatelet therapy, such as aspirin, in patients at high
      risk for a cerebrovascular event. Third, an abundance of data suggests that lipid
      lowering therapy with a statin reduces stroke risk in most moderate- to high-risk
      patients regardless of baseline cholesterol levels. Together, these data suggest
      that intensive therapy with agents from multiple drug classes that target two or
      more risk factors for cerebrovascular disease may provide additive-or even
      synergistic-reductions in stroke risk.

PMID- 17436824
TI  - Key bioavailability features of a new extended-release formulation of minocycline
      hydrochloride tablets.
AB  - For a long time, minocycline has been recognized as highly efficacious for the
      treatment of acne vulgaris but with use-limiting acute vestibular adverse events
      (AVAEs). Based on the concept that lowered overall systemic exposure to
      minocycline should reduce unwanted side effects, a program was initiated to
      develop a modified-release formulation for clinical testing. An extended-release
      (ER) minocycline hydrochloride tablet formulation was developed that demonstrated
      delayed time of maximum concentration (tmax, 3 1/2 - 4 hours) compared with a
      nonmodified-release minocycline (tmax, 2 1/4 - 3 hours), and a lower maximum
      concentration of drug (cmax) in the blood (90%) compared with nonmodified-release
      formulations. At steady state (day 6), the ER-minocycline formulation had a 0- to
      24-hour area under the curve (AUC(0-24)) and cmax of 33.32 microg x h/mL and 2.63
      microg/mL, respectively, compared with 46.35 micro x h/mL and 2.92 microg/mL,
      respectively, for the nonmodified-release minocycline. These studies demonstrated
      that the new ER-minocycline hydrochloride formulation is not bioequivalent to the
      immediate-release (IR) minocycline hydrochloride formulation currently on the
      market. The favorable pharmacokinetic profile of ER minocycline also was not
      affected by concomitantly ingested food, including dairy products.

PMID- 17436825
TI  - Dose-ranging efficacy of new once-daily extended-release minocycline for acne
      vulgaris.
AB  - A multicenter, 12-week, randomized, double-blinded, placebo-controlled, dose
      ranging study was conducted in 233 subjects with moderate to severe facial acne
      vulgaris to determine the lowest effective once-daily oral dose of a new extended
      release (ER) minocycline hydrochloride formulation with the safest adverse effect
      profile. Subjects randomly were assigned to treatment with daily dosages of ER
      minocycline 1-, 2-, or 3-mg/kg tablets, or daily placebo tablets, for 84 days. At
      the end of the 12 weeks, the number of inflammatory lesions decreased
      approximately 50% from baseline levels in the dose groups. No dose-dependent
      effect was observed, with the percentage decrease in the number of inflammatory
      lesions in the 1-mg/kg treatment group being equal to or greater than higher
      doses. The pairwise difference between the ER-minocycline 1 mg/kg and placebo
      groups in the percentage decrease in inflammatory lesions was statistically
      significant (P = .015). Acute vestibular adverse events (AVAEs) appeared to be
      dose proportional, with the incidence being similar in the lowest (1 mg/kg)
      dosing group (24%) and in the placebo group (26%). Higher-dose regimens were
      associated with a higher incidence of central nervous system side effects and
      AVAEs. A 1-mg/kg daily dosage of the new ER-minocycline formulation is the lowest
      effective dose with the safest side effect profile, with higher-dose regimens
      offering no substantial therapeutic advantages.

PMID- 17436827
TI  - Traveling at the speed of life.

PMID- 17436826
TI  - Safety and efficacy of a new extended-release formulation of minocycline.
AB  - The complete safety and efficacy of a new extended-release (ER) minocycline
      hydrochloride formulation were assessed in an analysis of a phase 2 dose-finding
      study and 2 phase 3 safety and efficacy studies. The studies were similar in
      design, subject populations, and shared common dose groups of subjects given ER
      minocycline 1 mg/kg daily or placebo over 12 weeks. The similar designs were
      prospective, multicenter, randomized, double-blinded, and placebo-controlled. A
      total of 1038 subjects with moderate to severe acne were available for the pooled
      analysis. Independently, each study showed that treatment with ER-minocycline
      significantly reduced (P < .001) the number of inflammatory lesions and
      significantly improved (P < .001) their Evaluator's Global Severity Assessment
      (EGSA) scores (phase 3 studies). Analysis of the pooled population confirmed the
      results of the individual studies. The percentage of subjects reporting acute
      vestibular adverse events (AVAEs) was comparable between those receiving the ER
      minocycline 1-mg/kg dose and placebo (approximately 10% of subjects in each
      group) for both the individual studies and the pooled population. It was
      concluded that a novel ER-minocycline formulation that delivers consistent levels
      of drug at a 1-mg/kg dose reduces dose-dependent AVAEs while reducing
      inflammatory lesions and improving the overall appearance of patients with acne
      vulgaris.

PMID- 17436828
TI  - Provider alert: requirements for employee education about false claims laws and
      whistleblower protections.

PMID- 17436829
TI  - Causation question.

PMID- 17436830
TI  - High time for a trauma system. Area experts believe a designated trauma system
      will save Arkansas lives, time and money.

PMID- 17436831
TI  - Improving communication to reduce readmissions: physicians, home health providers
      must work as a team.

PMID- 17436832
TI  - Use of clopidogrel in coronary artery disease.
AB  - Clopidogrel has an established and important role in the management of patients
      with coronary artery disease after an acute event. It is generally a well
      tolerated drug. The major common problem associated with its use is the increased
      incidence of bleeding complications during or after coronary artery bypass graft
      surgery when clopidogrel is used within five days before surgery. For this
      reason, it is recommended to stop clopidogrel at least five days, and preferably
      one week before surgery.

PMID- 17436833
TI  - When children sexually abuse other children.
AB  - Sexual behaviors in preschool and school age children range from developmentally
      expected behaviors to those that may be classified as abusive to other children.
      This article discusses Arkansas statistics on the incidence of children with
      problematic sexual behaviors, proposed typologies for these behaviors, and the
      relationship of sexual acting out to sexual victimization. We also address
      assessment and treatment referral options for the child with sexual behavior
      problems as well as physician responsibilities for reporting to the Child Abuse
      Hotline and managing suspected sexual abuse victimization.

PMID- 17436834
TI  - Concept evolution in sensory integration: a proposed nosology for diagnosis.

PMID- 17436835
TI  - Identifying gravitational insecurity in children: a pilot study.
AB  - OBJECTIVE: This study developed an observational assessment of gravitational
      insecurity (GI), the GI Assessment, and examined its preliminary reliability and
      validity evidence. METHOD: The GI Assessment consisted of 15 activities that
      created conditions characterized as fear-inducing for children with gravitational
      insecurity. Three behavioral categories-avoidance, emotional, and postural
      responses--were scored for each activity. Participants were 18 children with
      gravitational insecurity, ages 5-10 years, and a matched group of children who
      were typically developing. Forty-eight preschoolers who were typically
      developing, ages 2-4 years, were examined for developmental trends. RESULTS:
      Significant differences were found between groups. Discriminant analysis
      classified 83% of the gravitationally insecure group and 100% of the typical
      group. Interrater reliability for the total test was .79. Performance of
      preschool children suggested a developmental age trend. CONCLUSION: The GI
      Assessment is a promising clinical tool for objectively identifying children with
      gravitational insecurity.

PMID- 17436836
TI  - Development of an assessment for ideational praxis.
AB  - OBJECTIVE: This study developed an assessment of ideational praxis, examined its
      psychometric properties, and analyzed age and gender trends in children who were
      typically developing. METHOD: Part 1 developed items and scoring criteria of the
      Test of Ideational Praxis (TIP) and examined interrater reliability and internal
      consistency. Part 2 studied performance of 80 typically developing children
      between ages 5 and 8 years. RESULTS: The TIP demonstrated acceptable interrater
      reliability (ICC = .85) and internal consistency (coefficient alpha = .74).
      Children who were typically developing demonstrated age and gender trends. Girls
      scored higher than boys, and older children scored higher than younger children.
      CONCLUSION: The TIP is the first objective assessment for identification of
      ideational abilities and is a reliable assessment tool. Further research is
      needed to validate the construct of ideation and examine the TIP's ability to
      discriminate between children with and without ideational difficulties.

PMID- 17436837
TI  - An examination of the relationships between motor and process skills and scores
      on the sensory profile.
AB  - OBJECTIVE: This quasi-experimental study sought to determine whether children
      with possible sensory processing deficits, as measured by the Sensory Profile,
      performed less well on an occupational performance measure compared to children
      with typical Sensory Profile scores. METHOD: Sixty-eight children were
      administered both the Assessment of Motor Process Skills (AMPS) and the Sensory
      Profile. After the assessments were completed, children were divided into two
      groups based on their Sensory Profile scores. RESULTS: Independent t tests
      indicated statistically significant differences between groups on the AMPS ADL
      [Activities of Daily Living] Motor and ADL Process measures (p < .05), with the
      children with atypical Sensory Profile scores showing more functional
      difficulties. Correlations revealed significant relationships among the measures.
      CONCLUSION: The results suggest that children identified with sensory processing
      deficits on the Sensory Profile are likely to experience some challenges in
      performing everyday occupations.

PMID- 17436838
TI  - Lessons learned: a pilot study on occupational therapy effectiveness for children
      with sensory modulation disorder.
AB  - OBJECTIVE: The purpose of this pilot study was to prepare for a randomized
      controlled study of the effectiveness of occupational therapy using a sensory
      integration approach (OT-SI) with children who have sensory processing disorders
      (SPD). METHOD: A one-group pretest, posttest design with 30 children was
      completed with a subset of children with SPD, those with sensory modulation
      disorder. RESULTS: Lessons learned relate to (a) identifying a homogeneous sample
      with quantifiable inclusion criteria, (b) developing an intervention manual for
      study replication and a fidelity to treatment measure, (c) determining which
      outcomes are sensitive to change and relate to parents' priorities, and (d)
      clarifying rigorous methodologies (e.g., blinded examiners, randomization,
      power). CONCLUSION: A comprehensive program of research is needed, including
      multiple pilot studies to develop enough knowledge that high-quality
      effectiveness research in occupational therapy can be completed. Previous
      effectiveness studies in OT-SI have been single projects not based on a unified
      long-term program of research.

PMID- 17436839
TI  - Development of the Sensory Processing Measure-School: initial studies of
      reliability and validity.
AB  - OBJECTIVE: The history and development of the Sensory Processing Measure-School
      are detailed, and findings of initial pilot studies are reported. METHOD:
      Multiple reviews, focus groups, case studies, and two pilot studies were used to
      develop the early versions of the tool. Internal consistency and discriminatory
      ability were examined. RESULTS: Internal consistency measured with Cronbach's
      alphas ranged from .93 to .99 in the first pilot study and .70 to .99 in the
      second pilot study. Children who were typically developing were correctly
      classified 92.3% of the time, and children with sensory issues were correctly
      classified 72% of the time. CONCLUSION: Initial results suggest that the tool is
      reliable and valid and discriminates children with and without sensory processing
      issues. Further research is under way with larger samples.

PMID- 17436840
TI  - Validating the diagnosis of sensory processing disorders using EEG technology.
AB  - OBJECTIVE: This study tested the assumption of sensory integration theory that
      states that a relationship exists between brain function and the behavioral
      manifestations of sensory integrative dysfunction. METHOD:
      Electroencephalographic measures were used to examine brain processing in 28
      children with sensory processing disorders (SPD) and 25 children who were
      typically developing, ages 5-12 years. RESULTS: Children with SPD demonstrated
      less sensory gating than children who were typically developing. A significant
      relationship between sensory gating and age was found in children who were
      typically developing but not in children with SPD. Brain activity correctly
      distinguished children with SPD from children who were typically developing with
      86% accuracy. CONCLUSION: These results present empirical evidence that children
      with SPD display unique brain processing mechanisms compared to children who are
      typically developing and provide external validity for the diagnosis of SPD.

PMID- 17436841
TI  - Sensory processing in children with and without autism: a comparative study using
      the short sensory profile.
AB  - OBJECTIVE: The purpose of this study is to investigate differences in sensory
      processing among age-matched children between ages 3 and 6 years with autism
      spectrum disorders (ASD) and those who are typically developing. METHOD: Reported
      sensory processing abilities of 281 children with ASD were compared to age
      matched peers who were typically developing, using the Short Sensory Profile
      (SSP). RESULTS: Ninety-five percent of the sample of children with ASD
      demonstrated some degree of sensory processing dysfunction on the SSP Total
      Score, with the greatest differences reported on the Underresponsive/ Seeks
      Sensation, Auditory Filtering, and Tactile Sensitivity sections. The ASD group
      also performed significantly differently (p < .001) on 92% of the items, total
      score, and all sections of the SSP. CONCLUSION: These findings, considered with
      similar published studies, begin to confirm the prevalence and types of sensory
      processing impairments in autism. Further research is needed to more clearly
      define patterns of sensory processing in people with ASD.

PMID- 17436842
TI  - How does sensory processing dysfunction affect play?
AB  - OBJECTIVE: This study investigated sensory processing dysfunction (SPD) and
      playfulness and the effect of intervention on playfulness. METHOD: Twenty
      children with SPD and 20 children who were typically developing took the Short
      Sensory Profile (SSP) and Test of Playfulness (ToP). Children with SPD took the
      praxis tests from the Sensory Integration and Praxis Tests (SIPT) and received 20
      intervention sessions. Correlations among measures and differences between mean
      scores of groups and pre-intervention and post-intervention were examined.
      RESULTS: Group ToP scores differed significantly; ToP did not increase post
      intervention. Correlations among ToP and SSP ranged from .36 to .72; ToP and
      SIPT, from -0.1 to -0.46. CONCLUSION: Modulation affects playfulness. Although
      intervention was not effective, both groups had high scores initially, making the
      finding difficult to interpret.

PMID- 17436843
TI  - The effect of sound-based intervention on children with sensory processing
      disorders and visual-motor delays.
AB  - This study investigated the effects of a sensory diet and therapeutic listening
      intervention program, directed by an occupational therapist and implemented by
      parents, on children with sensory processing disorders (SPD) and visual-motor
      delays. A convenience sample was used of 10 participants, ages 5 to 11 years,
      with SPD and visual-motor delays. In the first phase, each participant completed
      a 4-week sensory diet program, then an 8-week therapeutic-listening and sensory
      diet program. The Sensory Profile was completed by the participants' parents
      before and after both study phases. The Draw-A-Person test, Developmental Test of
      Visual Motor Integration (VMI), and Evaluation Tool of Children's Handwriting
      (ETCH) were administered before and after each phase. Over 12 weeks, the
      participants exhibited significant improvement on the Sensory Profile, increasing
      a mean of 71 points. Parents reported improvements in their children's behaviors
      related to sensory processing. Scores on the VMI visual and ETCH legibility
      scales also improved more during the therapeutic listening phase. Therapeutic
      listening combined with a sensory diet appears effective in improving behaviors
      related to sensory processing in children with SPD and visual-motor impairments.

PMID- 17436844
TI  - Fidelity in sensory integration intervention research.
AB  - OBJECTIVE: We sought to assess validity of sensory integration outcomes research
      in relation to fidelity (faithfulness of intervention to underlying therapeutic
      principles). METHOD: We identified core sensory integration intervention elements
      through expert review and nominal group process. Elements were classified into
      structural (e.g., equipment used, therapist training) and therapeutic process
      categories. We analyzed 34 sensory integration intervention studies for
      consistency of intervention descriptions with these elements. RESULTS: Most
      studies described structural elements related to therapeutic equipment and
      interveners' profession. Of the 10 process elements, only 1 (presentation of
      sensory opportunities) was addressed in all studies. Most studies described fewer
      than half of the process elements. Intervention descriptions in 35% of the
      studies were inconsistent with one process element, therapist-child
      collaboration. CONCLUSION: Validity of sensory integration outcomes studies is
      threatened by weak fidelity in regard to therapeutic process. Inferences
      regarding sensory integration effectiveness cannot be drawn with confidence until
      fidelity is adequately addressed in outcomes research.

PMID- 17436845
TI  - A randomized controlled pilot study of the effectiveness of occupational therapy
      for children with sensory modulation disorder.
AB  - OBJECTIVE: A pilot randomized controlled trial (RCT) of the effectiveness of
      occupational therapy using a sensory integration approach (OT-SI) was conducted
      with children who had sensory modulation disorders (SMDs). This study evaluated
      the effectiveness of three treatment groups. In addition, sample size estimates
      for a large scale, multisite RCT were calculated. METHOD: Twenty-four children
      with SMD were randomly assigned to one of three treatment conditions; OT-SI,
      Activity Protocol, and No Treatment. Pretest and posttest measures of behavior,
      sensory and adaptive functioning, and physiology were administered. RESULTS: The
      OT-SI group, compared to the other two groups, made significant gains on goal
      attainment scaling and on the Attention subtest and the Cognitive/Social
      composite of the Leiter International Performance Scale-Revised. Compared to the
      control groups, OT-SI improvement trends on the Short Sensory Profile, Child
      Behavior Checklist, and electrodermal reactivity were in the hypothesized
      direction. CONCLUSION: Findings suggest that OT-SI may be effective in
      ameliorating difficulties of children with SMD.

PMID- 17436846
TI  - Occupational therapy using a sensory integrative approach: a case study of
      effectiveness.
AB  - OBJECTIVE: This article presents a case report of a child with poor sensory
      processing and describes the disorders impact on the child's occupational
      behavior and the changes in occupational performance during 10 months of
      occupational therapy using a sensory integrative approach (OT-SI). METHOD:
      Retrospective chart review of assessment data and analysis of parent interview
      data are reviewed. Progress toward goals and objectives is measured using goal
      attainment scaling. Themes from parent interview regarding past and present
      occupational challenges are presented. RESULTS: Notable improvements in
      occupational performance are noted on goal attainment scales, and these are
      consistent with improvements in behavior. Parent interview data indicate
      noteworthy progress in the child's ability to participate in home, school, and
      family activities. CONCLUSION: This case report demonstrates a model for OT-SI.
      The findings support the theoretical underpinnings of sensory integration theory:
      that improvement in the ability to process and integrate sensory input will
      influence adaptive behavior and occupational performance. Although these findings
      cannot be generalized, they provide preliminary evidence supporting the theory
      and the effectiveness of this approach.

PMID- 17436847
TI  - Sensory processing disorders in a nonhuman primate model: evidence for
      occupational therapy practice.
AB  - Evaluation of sensory processing function serves as a critical component of
      treatment planning and implementation of intervention in pediatric occupational
      therapy practice. We developed a Sensory Processing Scale for Monkeys (SPS-M),
      based on human tests, that measures behavioral responses to a series of tactile
      stimuli. This assessment has been used to assess sensory processing in adult
      rhesus monkeys exposed to prenatal alcohol, stress, or postnatal lead. Control
      monkeys from undisturbed pregnancies showed a habituation pattern, prenatally
      stressed monkeys showed sensitization, and prenatal alcohol-exposed monkeys
      showed relatively high responsiveness without habituation across trials. Lead
      exposed monkeys showed sensitization compared to nonlead-exposed controls, and
      chelation reduced the sensitization in lead-exposed animals. Aversive
      responsiveness was associated with up-regulated striatal dopamine receptor
      binding measured with positron emission tomography.

PMID- 17436848
TI  - Goal attainment scaling as a measure of meaningful outcomes for children with
      sensory integration disorders.
AB  - Goal attainment scaling (GAS) is a methodology that shows promise for application
      to intervention effectiveness research and program evaluation in occupational
      therapy (Dreiling & Bundy, 2003; King et al., 1999; Lannin, 2003; Mitchell &
      Cusick, 1998). This article identifies the recent and current applications of GAS
      to occupational therapy for children with sensory integration dysfunction, as
      well as the process, usefulness, and problems of application of the GAS
      methodology to this population. The advantages and disadvantages of using GAS in
      single-site and multisite research with this population is explored, as well as
      the potential solutions and future programs that will strengthen the use of GAS
      as a measure of treatment effectiveness, both in current clinical practice and in
      much-needed larger, multisite research studies.

PMID- 17436849
TI  - Factors influencing the loss of beta-cell mass in islet transplantation.
AB  - Recent advances in clinical islet transplantation have clearly demonstrated that
      this procedure can provide excellent glycemic control and often insulin
      independence in a population of patients with type 1 diabetes. A key limitation
      in the widespread application of clinical islet transplantation is the
      requirement of 10,000 islet equivalents/kg in most recipients, generally derived
      from two or more cadaveric donors. It has been determined that a majority of the
      transplanted islets fail to engraft and become fully functional. In this review
      article, the factors that contribute to this early loss of islets following
      transplantation are discussed in depth.

PMID- 17436850
TI  - Detection of microbial contamination during human islet isolation.
AB  - Current good manufacturing practice (cGMP) islet processing facilities provide an
      ultraclean environment for the safe production of clinical grade islets for
      transplantation into immunosuppressed diabetic recipients. The objective of this
      study was to monitor the rate of microbial contamination in islet products after
      implementation of good manufacturing practice conditions. Fluid samples for
      microbial contamination were collected at the following steps: from the pancreas
      transport solution upon arrival of the organ (n=157), after surface
      decontamination of the pancreas with antiseptic agents (n=89), from islet
      supernatant at the end of the isolation (n=104), and from islet supernatant as a
      final transplantable product after culture (n=53). Bacterial, fungal, and
      mycoplasma cultures were conducted for 2, 2, and 3 weeks, respectively. Microbial
      contamination was detected in 31% of transport solution. The contamination was
      not associated with the presence of the duodenum during the preservation, cold
      ischemia time, or procurement team (local vs. distant). Surface decontamination
      of the pancreas resulted in clearance of 92% of the microbial contamination. Six
      preparations at the end of the isolation revealed microbial growth. All were de
      novo contamination during the processing. Fifty-three preparations that met our
      release criteria in terms of product sterility were transplanted into type 1
      diabetic patients. In two instances, positive culture of the islet preparation
      was reported after transplantation had occurred. No patient showed any clinical
      findings suggestive of infection or any radiological abnormalities suggestive of
      abscess; a single dose of antibiotic coverage was given routinely to recipients
      prior to islet infusion. Although transport solution carries a high risk of
      microbial contamination, most contaminants become undetectable during islet
      processing. Microbial contamination in final products is rare, but de novo
      contamination still occurs during processing even under cGMP conditions.

PMID- 17436851
TI  - Transient beneficial effects of exendin-4 treatment on the function of
      microencapsulated mouse pancreatic islets.
AB  - Transplantation of microencapsulated islets may reduce hyperglycemia in the
      absence of immunosuppression. However, the efficiency of microencapsulated islet
      transplantation is low, requiring more islets to achieve normoglycemia than in
      vascularized islet transplantation. Exendin-4 (a glucagon-like receptor agonist)
      has been previously shown to improve islet transplantation outcome in rodents. We
      investigated whether this treatment would enhance the function of
      microencapsulated islets in vitro and in vivo. Encapsulated or naked islets were
      cultured with or without exendin-4 for 72 h. To test in vitro function, insulin
      release and glucose oxidation rates were measured in the absence or presence of
      exendin-4. In addition, in vivo function of a minimal mass of 350
      microencapsulated islets was assessed by syngeneic transplantation into the
      peritoneal cavity of alloxan-diabetic mice. Glucose oxidation rates of
      microencapsulated islets were improved by 72-h pretreatment with exendin-4.
      Insulin release was increased both acutely after glucose stimulation and over a
      40-h culture period by the presence of exendin-4. Transplantation outcome of
      microencapsulated islets cultured with exendin-4 was initially improved, but by
      day 7 there were no differences compared with control cultured microencapsulated
      islets. Culture of microencapsulated islets with exendin-4 increases glucose
      oxidation and insulin release rates, but the increased function seen in vitro was
      not enough to improve the long term outcome in a transplantation model.

PMID- 17436852
TI  - Resolution of severe atopic dermatitis after tacrolimus withdrawal.
AB  - Tacrolimus is an immunosuppressive agent used in solid organ and islet
      transplantation. Its topical form has shown benefit in the treatment of
      inflammatory skin conditions. Although tacrolimus has a wide spectrum of side
      effects, dermatological complications related to systemic tacrolimus therapy are
      limited in the literature. Atopic dermatitis (AD) is a chronic pruritic cutaneous
      condition that usually begins in infancy and is characterized by an increased Th2
      response. We report the case of a patient with type 1 diabetes mellitus (T1DM)
      and history of AD latent for 10 years who developed severe dermatitis and
      alopecia 5 months after undergoing allogeneic islet transplantation and
      initiating a steroid-free immunosuppressive regimen with sirolimus and tacrolimus
      maintenance. After exclusion of other possible causes for the progression and
      exacerbation of the clinical presentation of AD, discontinuation of tacrolimus
      and introduction of mycophenolate mofetil resulted in full remission of the
      symptoms. The beneficial effects of tacrolimus withdrawal suggest a cause-effect
      relationship between this adverse event and the utilization of the drug. Islet
      graft function remained stable after modification of the therapeutic regimen
      (stable glycemic control and unchanged C-peptide).

PMID- 17436853
TI  - Transplantation of cultured adult porcine full-thickness retina.
AB  - In this study we wanted to examine how an adult neuroretina from an animal with
      an eye similar to the human one survives in vitro. We also wanted to investigate
      how the culture process affects the adult retina when used in a transplantation
      paradigm. Full-thickness neuroretinal sheets from adult porcine eyes were
      dissected into pieces measuring 3 mm in diameter. These were kept in culture for
      1-3 days. After this time, the explants were fixed or transplanted subretinally
      to adult pigs, which were killed after 72-74 days. Transplanted eyes, as well as
      tissue kept in culture only, were processed for hematoxylin and eosin staining
      and immunohistochemistry. Explants kept 1 day in vitro (DIV) displayed the normal
      morphology. In these specimens, single pyknotic cells were evident in the outer
      nuclear layer (ONL) and ganglion cell layer, but were more frequent in the inner
      nuclear layer (INL). After longer times in vitro, severe degenerative changes
      appeared. Transplanted explants kept 1 DIV prior to transplantation exhibited
      normal retinal lamination in two out of four specimens. Transducin and recoverin
      labeling revealed photoreceptors with inner segments in these grafts. Rod bipolar
      cells displayed a normal morphology. Vertically arranged Muller cells were also
      seen in the laminated grafts. Two of the three transplants kept 2 DIV displayed
      minimal lamination. Eyes with transplants kept 3 DIV prior to transplantation
      displayed degenerated grafts in all eyes. This study shows that adult porcine
      neuroretinal explants kept in culture for 1 day display a normal morphology in
      their major part. Additionally, 1-day explants can survive transplantation with
      retained morphology even after several months. This indicates the possibility of
      storing adult donor tissue between harvest and transplantation. The culture
      system may also be used in the future as a tool for manipulating retinal donor
      tissue prior to transplantation.

PMID- 17436854
TI  - Induction of neurotrophin expression via human adult mesenchymal stem cells:
      implication for cell therapy in neurodegenerative diseases.
AB  - In animal models of neurological disorders for cerebral ischemia, Parkinson's
      disease, and spinal cord lesions, transplantation of mesenchymal stem cells
      (MSCs) has been reported to improve functional outcome. Three mechanisms have
      been suggested for the effects of the MSCs: transdifferentiation of the grafted
      cells with replacement of degenerating neural cells, cell fusion, and
      neuroprotection of the dying cells. Here we demonstrate that a restricted number
      of cells with differentiated astroglial features can be obtained from human adult
      MSCs (hMSCs) both in vitro using different induction protocols and in vivo after
      transplantation into the developing mouse brain. We then examined the in vitro
      differentiation capacity of the hMSCs in coculture with slices of neonatal brain
      cortex. In this condition the hMSCs did not show any neuronal
      transdifferentiation but expressed neurotrophin low-affinity (NGFR(p75)) and high
      affinity (trkC) receptors and released nerve growth factor (NGF) and neurotrophin
      3 (NT-3). The same neurotrophin's expression was demonstrated 45 days after the
      intracerebral transplantation of hMSCs into nude mice with surviving astroglial
      cells. These data further confirm the limited capability of adult hMSC to
      differentiate into neurons whereas they differentiated in astroglial cells.
      Moreover, the secretion of neurotrophic factors combined with activation of the
      specific receptors of transplanted hMSCs demonstrated an alternative mechanism
      for neuroprotection of degenerating neurons. hMSCs are further defined in their
      transplantation potential for treating neurological disorders.

PMID- 17436855
TI  - Plasma as a scaffold for regeneration of neural precursor cells after
      transplantation into rats with spinal cord injury.
AB  - The present study investigated whether plasma could be useful as a scaffold for
      cell transplantation in rats with spinal cord injury (SCI). Transplantation of
      cells with plasma promoted the recovery of SCI-induced motor dysfunction.
      Immunohistochemical analysis revealed that the grafted cells had differentiated
      into the neural lineage. When dissociated neural precursor cells were cultured
      with plasma, extensive neurite outgrowth was observed along with increased
      expression of p35 and NF68. Neural markers were also expressed by the cultured
      cells. Culture with plasma reduced thymidine incorporation, but promoted cell
      growth and increased the RNA contents. These findings suggest that the cells
      underwent differentiation into neurons in the presence of plasma. In conclusion,
      plasma could be a promising scaffold for cell transplantation therapy.

PMID- 17436856
TI  - Long-term maintenance of the drug transport activity in cryopreservation of
      microencapsulated rat hepatocytes.
AB  - Transplantation of isolated hepatocytes has been proposed to compensate for
      essential functions lacking in liver failure or for genetic defects that alter a
      specific liver metabolic pathway. Hepatocyte utilization for these purposes would
      be facilitated with a reliable, reproducible, and effective method of long-term
      hepatocyte storage. We have recently developed a simple new system for
      cryopreservation of hepatocytes that encapsulates alginate microspheres and
      maintains liver-specific function. The aim of this study was to elucidate the
      transport and drug-metabolizing enzyme activities of cryopreserved
      microencapsulated hepatocytes stored for a long time. Morphological examinations
      showed there is no apparent injury of the hepatocytes during cryopreservation
      processes. A drug-metabolizing enzyme (testosterone 6beta-hydroxylase, a specific
      probe for CYP3A2) and drug transport activities [salicylate, allopurinol, and
      prostaglandin E2 (PGE2), typical substrates of rOat2] in cryopreserved
      microencapsulated hepatocytes were maintained up to 120 days. Our results thus
      demonstrate for the first time that cryopreservation of primary rat hepatocytes
      by the encapsulation technique allows long-term retention of drug metabolism and
      drug transport activities.

PMID- 17436857
TI  - Tea polyphenol inhibits allostimulation in mixed lymphocyte culture.
AB  - Green tea polyphenols are known to protect allogenic donor tissues from acute
      rejection by their recipients. This immunosuppressive effect may be generated by
      a unique chemical property of the major component, epigallocatechin-o-gallate
      (EGCG), which can block specific cell surface molecules of the donor tissues. To
      test this hypothesis, we examined the effects of EGCG on the murine mixed
      lymphocyte reactions. EGCG treatment of stimulator cells significantly attenuated
      the proliferation of responder T cells. The proliferation did not recover upon
      the secondary stimulations by fresh untreated cells or exogenous IL-2. Flow
      cytometric analyses showed that EGCG treatment decreased the staining intensities
      of various cell surface molecules including MHC II, which plays a major role in
      antigen presentation, and B7.1, B7.2, and their ligand, CD28, which are required
      for costimulatory signals in T-cell activation. These results suggest that an
      anergic state of alloreactive T cells may be induced by either weakening of
      antigen signaling or blockage of costimulatory signals with EGCG. Other possible
      mechanisms behind the immunosuppressive effect and a potential use of EGCG
      treatment of donor tissues in transplantation medicine are discussed.

PMID- 17436858
TI  - Functional and phenotypic alteration of intrasplenic lymphocytes affected by
      mesenchymal stem cells in a murine allosplenocyte transfusion model.
AB  - Previous data have demonstrated that mesenchymal stem cells (MSCs) can exert
      immunomodulatory activity in vitro, in which of the process nearly all kinds of
      immune cell subsets are involved. However, there is still a paucity of
      information about whether and why MSCs inhibit the ongoing immune responses in
      vivo. Working in a murine splenocyte transfusion model across the major
      histocompatibility barrier (C57BL/6 -BALB/c, H2b --> H2d), we have found that MSC
      coinfusion prolongs the mean survival time (MST) of the recipient mice in a dose
      dependent manner and reduces graft-versus-host-associated histopathology in
      comparison to the allosplenocyte transfusion controls. In vivo eGFP tracing with
      polymerase chain reaction analysis revealed that grafted MSCs could migrate and
      settle into the lungs, spleen, liver, intestine, and skin shortly after
      administration. Further investigations into the functional characteristics of
      intrasplenic lymphocytes showed that their proliferation and cytotoxic activity
      against P815 cells (H2d) were significantly restrained by MSC cotransfer. FACS
      analysis demonstrated that MSC infusion not only increased the proportion of CD4+
      subset but also decreased that of CD8+ cells at the belated observation points,
      resulting in the increase of the ratio of CD4+/CD8+ cells. Also, in contrast to
      the slight increase of the proportion of CD4+CD25+ T regulatory cells (Tregs) in
      MSC cotransfer mice, the ratio of Tregs/CD8+ cells was dramatically elevated.
      Furthermore, RT-PCR analysis on the cytokine array of IL-2, IL-4, IL-12, TNF
      alpha, and TGF-beta in recipient splenocytes implied the Thl to Th2 polarization.
      Therefore, it is deducible that alteration in the proportions of different T
      lymphocyte subsets may be one of the main mechanisms by which grafted MSCs
      suppress the ongoing immune responses in vivo. The study here might provide some
      new clues for the design of therapeutic approaches for MSC transplantation.

PMID- 17436859
TI  - [Appropriate use of anti-MRSA drugs (discussion)].

PMID- 17436860
TI  - [Susceptibility of clinical isolates from primary care clinics to oral
      antibacterial agents].
AB  - The antimicrobial susceptibility of clinical isolates from specimens of patients
      in primary care clinics in 2005 was investigated by determining the minimum
      inhibitory concentrations of oral antibacterial agents. The numbers of test
      strains were 550 for Gram-positive aerobes, 700 for Gram-negative aerobes, and
      150 for anaerobes. Cefcapene (CFPN), cefditoren (CDTR), and cefteram (CFTM)
      showed the most potent activities against Staphylococcus spp. and Streptococcus
      spp. among the cephems tested and moxifloxacin (MFLX) and tosufloxacin among the
      new quinolones. Although the new quinolones generally showed potent activities
      against these species, resistant strains were frequently detected in methicillin
      resistant Staphylococcus aureus. In addition, 70% or more of Streptococcus
      pneumoniae isolates were intermediate or resistant to macrolides. Cephems showed
      good activities against aerobic Gram-negative bacteria except for Proteus spp.
      Specifically, CFPN, CDTR, and CFTM showed the most potent activity against
      Haemophilus influenzae among the cephems tested. The new quinolones showed potent
      activities against Gram-negative bacteria, especially H. influenzae and Moraxella
      catarrhalis, but not against Proteus mirabilis and Providencia spp. When compared
      with the susceptibilities of clinical isolates from tertiary care hospitals,
      found in other research, differences were noted, for example, there was a lower
      frequency of quinolone-resistant strains of methicillin-susceptible S. aureus but
      a higher frequency of macrolide-resistant strains of Streptococcus pyogenes.
      Therefore, to accurately grasp susceptibility trends, well-focused surveillance
      studies are necessary.

PMID- 17436861
TI  - [Comparison of antimicrobial and bactericidal activities and postantibiotic
      effects of macrolides antibiotics against clinical isolates, and examination of
      shape alteration by scanning electron microscope].
AB  - We examined antibacterial activities of 4 kinds of macrolides (MLs), erythromycin
      (EM), clarithromycin (CAM), azithromycin (AZM) and rokitamycin (RKM), against 4
      bacterial species of clinical strains isolated in 2004. Bacterial isolates used
      were 51 strains of methicillin-susceptible Staphylococcus aureus (MSSA), 20 of
      Streptococcus pyogenes, 68 of Streptococcus agalactiae, and 120 of Streptococcus
      pneumoniae. Macrolide resistance genes, ermB and mefE, in macrolide-resistant S.
      pyogenes and S. agalactiae, and all of pneumococci were analyzed by PCR.
      Antimicrobial activities against macrolide-susceptible MSSA of EM and CAM, were
      more potent than those of RKM. By contrast, against S. pneumoniae, RKM was more
      effective than EM, CAM and AZM. Against S. pyogenes and S. agalactiae, 4
      antibiotics showed similar antimicrobial activities. Twelve, 1 and 2 strains of
      MSSA, S. pyogenes and S. agalactiae, respectively, were resistant to EM, CAM and
      AZM, whereas RKM was active to almost, but not quite, of them. Among 120 strains
      of S. pneumoniae, 76 (63.3%) were resistant to EM (MIC; > or = 0.5 microg/mL),
      and 23, 15 and 28 strains were highly resistant (MIC; > 128 microg/mL) to EM, CAM
      and AZM, respectively. By contrast, for RKM, there were far fewer resistant
      strains, and there was no highly resistant strain. PCR analyses of macrolide
      resistant genes revealed that 1 resistant strain of S. pyogenes and 2 of S.
      agalactiae carried mefE and ermB, respectively. In the case of S. pneumoniae, 59,
      19 and 5 strains, respectively, carried ermB, mefE and both ermB and mefe. We
      also studied about bactericidal activities and postantibiotic effects (PAE) of
      MLs using macrolide-susceptible, and ermB- and mefE-carrying S. pneumoniae, and
      observed morphological alterations of the strains treated with the drugs by a
      scanning electron microscope. It was demonstrated that RKM had superior
      bactericidal activities and PAE than other 3 drugs, and potent destructive
      effects to all of 3 strains.

PMID- 17436862
TI  - [Efficacy of injectable carbapenems for respiratory infections caused by
      Streptococcus pneumoniae and Haemophilus influenzae with Monte Carlo simulation].
AB  - Streptococcus pneumoniae and Haemophilus influenzae are two major pathogens for
      respiratory tract infections, and those infections might cause critically ill
      patients. We performed the analysis with Monte Carlo Simulation for 253 strains
      of S. pneumoniae and 309 strains of H. influenzae isolated in the Gifu prefecture
      in 2002 and 2003. As for the pneumococcal infection in patient with good
      immunological response, good clinical effect might be obtained by
      panipenem/betamipron (PAPM/BP) 500 mg, imipenem/cilastatin (IPM/CS) 500 mg,
      meropenem (MEPM) 500 mg and biapenem (BIPM) 300 mg, b.i.d., while for
      immunocompromised hosts or infections by penicillin-resistant Streptococcus
      pneumoniae (PRSP), PAPM/BP, 500 mg, b.i.d., or IPM/CS 500 mg, MEPM 500 mg, t.i.d.
      or BIPM 600 mg, b.i.d. would be recommended. As for the infections caused by H.
      influenzae, in patient with good immunological response, good clinical effect
      might be obtained by MEPM 500 mg, b.i.d or PAPM/BP 1000 mg, b.i.d., while for
      immunocompromised hosts, MEPM 500 mg, t.i.d. would be recommended. Monte Carlo
      Simulation would be one of the useful tools for appropriate antimicrobial
      chemotherapy also against respiratory infections.

PMID- 17436863
TI  - Dying in nursing homes.

PMID- 17436864
TI  - Barriers to safe medication administration in the nursing home--exploring staff
      perceptions and concerns about the medication use process.
AB  - The purpose of this study was to explore staff perceptions and concerns about the
      medication use process in the nursing home setting. A total of 76 staff members
      from 5 nursing homes in 3 Midwestern states participated in key informant
      interviews and focus groups. Common themes included issues related to
      communication, competing demands, and the challenges of a paper-based medication
      administration record. Concerns frequently were associated with the timeliness
      and accuracy of the medication administration process. Recognition of staff
      concerns are an important first step in improving the nursing home medication use
      process. Staff insight provided clarification related to impediments to safe
      medication practices. This study provides insight into how technology can improve
      the nursing home medication use process.

PMID- 17436865
TI  - Relationship between assault frequency and length of hospitalization in older
      patients with dementia--determining the maximum benefit of inpatient treatment.
AB  - In this quantitative study, the author examined the relationship between duration
      of hospitalization and frequency of assaultive behavior in 42 older long-term
      patients with dementia in a Canadian psychiatric hospital. The study instrument
      used for data collection was existing incident reporting forms routinely
      completed in Canadian regional psychiatric hospitals. A secondary analysis was
      conducted using data previously collected on a regular basis by the psychiatric
      hospital serving as the study site. A significant negative correlation was found
      between the number of assaults committed and the number of months spent in the
      hospital, with significantly fewer assaults occurring in the second year of
      hospitalization compared with the first year. Male patients were observed to be
      significantly more assaultive than female patients. Findings suggest that the
      maximum benefit for patients hospitalized for assaultive behavior is obtained
      during the first 2 years of inpatient treatment and that patients within this
      population who are no longer assaultive may be more appropriately cared for in
      nursing homes. Based on these findings, resources should be allocated to assist
      with the transition of formerly assaultive patients with dementia from a
      psychiatric hospital to a nursing home. This scenario forecasts the development
      of a challenging new role for nurses.

PMID- 17436866
TI  - Family participation in care plan meetings: promoting a collaborative
      organizational culture in nursing homes.
AB  - In this study, the author evaluated a project in The Netherlands that aimed to
      promote family members' participation in care plan meetings at a psychogeriatric
      nursing home. The small-scale pilot project, which was conducted in four wards of
      the nursing home, was designed to involve families in health care decisions by
      allowing family members to participate in care plan meetings. Both qualitative
      (participant observation and interview) and quantitative (observation matrix and
      index analysis) approaches were used to evaluate the project. Findings showed
      family members were involved in approximately half of the interactions, and many
      of the questions family members asked were not about the illness, but about its
      effects. This study indicates there is a need for family members to participate
      in the multidisciplinary care plan meeting.

PMID- 17436867
TI  - Death in the nursing home: resident, family, and staff perspectives.
AB  - The actual experience of dying in the United States is far different from the
      expressed desires of most Americans. Although most Americans express a preference
      for dying at home, 73% of Americans die in medical institutions, with 23% dying
      in nursing homes (Teno, 2004). In this article, the author examines end-of-life
      care in the nursing home. A literature review identified more than 100 published
      articles relevant to end-of-life care in nursing homes. Of these, the author
      evaluated empirical research studies from the perspectives of residents, family
      members, and nursing home staff with findings specific to seriously ill nursing
      home residents. By identifying problematic issues and contributing factors,
      nurses can modify their practice to improve end-of-life care and substantially
      reduce suffering for nursing home residents and their families.

PMID- 17436868
TI  - Informal caregiving and Body Mass Index among older adults.
AB  - The authors sought to obtain nationally representative estimates of the time of
      informal caregiving provided to older adults classified into the four standard
      Body Mass Index (BMI) classifications. They estimated multivariate regression
      models using data from the 2000 Health and Retirement Study to determine the
      weekly hours of informal caregiving for older adults classified into the four
      standard BMI classifications. In the fully adjusted models, being underweight was
      associated with receiving significantly more informal care, however, obesity was
      not associated with more informal care. The implications of these findings are
      discussed in terms of nursing practice and research to prevent weight loss and
      frailty.

PMID- 17436869
TI  - Use of Magnetorheological fluid in a force feedback glove.
AB  - Magnetorheological fluid (MRF) is a smart material that has the property of
      changing its viscosity when exposed to a magnetic field. By placing this fluid
      into a sealed cylinder with an electromagnet piston as a core, a controllable
      resistance motion dampener can be created. A novel exoskeleton mechanical power
      transmission system was designed, utilizing rapid prototype parts, to transmit
      these resistive forces to the user's fingertips. A first iteration force feedback
      glove was developed and tested on human subjects for overall usability. The
      eventual goal of the system is to provide an alternative force producing system
      for exercises and rehabilitation. The entire system is lightweight, low power,
      and easily portable.

PMID- 17436870
TI  - A virtual reality environment for designing and fitting neural prosthetic limbs.
AB  - Building and testing novel prosthetic limbs and control algorithms for functional
      electrical stimulation (FES) is expensive and risky. Here, we describe a virtual
      reality environment (VRE) to facilitate and accelerate the development of novel
      systems. In the VRE, subjects/patients can operate a simulated limb to interact
      with virtual objects. Realistic models of all relevant musculoskeletal and
      mechatronic components allow the development of entire prosthetic systems in VR
      before introducing them to the patient. The system is used both by engineers as a
      development tool and by clinicians to fit prosthetic devices to patients.

PMID- 17436871
TI  - AudioMUD: a multiuser virtual environment for blind people.
AB  - A number of virtual environments have been developed during the last years. Among
      them there are some applications for blind people based on different type of
      audio, from simple sounds to 3-D audio. In this study, we pursued a different
      approach. We designed AudioMUD by using spoken text to describe the environment,
      navigation, and interaction. We have also introduced some collaborative features
      into the interaction between blind users. The core of a multiuser MUD game is a
      networked textual virtual environment. We developed AudioMUD by adding some
      collaborative features to the basic idea of a MUD and placed a simulated virtual
      environment inside the human body. This paper presents the design and usability
      evaluation of AudioMUD. Blind learners were motivated when interacted with
      AudioMUD and helped to improve the interaction through audio and interface design
      elements.

PMID- 17436872
TI  - Technical feasibility of teleassessments for rehabilitation.
AB  - BACKGROUND: technical feasibility was evaluated for conducting standard motor
      assessment instruments in a remote setting. Remote assessment was compared to co
      located assessment for five clinical evaluation instruments: joint range-of
      motion (ROM), manual muscle test (MMT), Berg sit-to-stand, Berg forward reach,
      and timed up and go (TUG). METHODS: co-located and remote rooms were in the same
      building connected by broadband video and audio. Ten subjects without impairments
      participated, but were given simulated impairments to mimic the patient
      population commonly seen in rehabilitation clinics. One therapist performed all
      co-located testing while another performed all remote assessments. Measurements
      followed standard clinical methods. Data were analyzed using repeated measures
      ANOVA and paired t-tests. RESULTS: no differences were found between co-located
      and remote assessments except for some cases using screen-based ROM measures.
      Remote ROM tests using snapshots and a virtual goniometer were preferred. A
      digital dynamometer added no additional information to a visually-based remote
      MMT assessment.

PMID- 17436873
TI  - Technical and patient performance using a virtual reality-integrated
      telerehabilitation system: preliminary finding.
AB  - Telerehabilitation is the provision of rehabilitation services at a distance by a
      therapist at a remote location. Integration with virtual reality (VR) is a
      relatively new addition to this field. This paper describes the technical and
      patient performance of a telerehabilitation application the remote console
      (ReCon) that is integrated with a VR system. The VR system consists of the
      Rutgers Ankle prototype robot, a local PC which is connected with a remote PC
      connected over the Internet. Six individuals in the chronic phase poststroke
      participated in a four week training program. They used the robot to interact
      with two VR simulations, while the therapist was in the same room during the
      first three weeks or in another room during the fourth week. Technical and
      patient performance was assessed in the transition from the third to the fourth
      week of training. Technical performance of the system was assessed based on
      bandwidth and lag of message transmission, which were found to be suitable for
      clinic-to-clinic communication. Patient performance (in terms of accuracy of
      ankle movement, exercise duration and training efficiency, mechanical power of
      the ankle, and number of repetitions) did not decrease during telerehabilitation
      in the fourth week. These preliminary findings over a short telerehabilitation
      intervention support the feasibility of remote monitoring of VR-based
      telerehabilitation without adverse effects on patient performance.

PMID- 17436874
TI  - Telerehabilitation using a virtual environment improves upper extremity function
      in patients with stroke.
AB  - In this paper, we describe our experience in designing a virtual environment
      based (VE) telerehabilitation system, and the results of a clinical study of the
      first 11 subjects with stroke to use the system. Our telerehabilitation system
      allows a therapist to conduct interactive VE treatment sessions remotely with a
      patient who is located at home. The system, software architecture, and
      development experience are described. Results of the clinical study on subjects
      with stroke showed significant improvements in upper extremity function following
      30 1-h VE treatment sessions as measured by three standard clinical tests: Fugl
      Meyer test of motor recovery (FM) (p < 0.0001), Wolf motor test (WMT) (p =
      0.0097, and shoulder strength (ShS) (p = 0.0027). Grip strength (GS) showed a
      trend toward improvement (p = 0.025). These changes were maintained, for the most
      part, at four-months follow-up (FM +7.6, WMT -18.4 s, ShS, +169%, GS, +53%).

PMID- 17436875
TI  - Telerehabilitation using the Rutgers Master II glove following carpal tunnel
      release surgery: proof-of-concept.
AB  - Carpal tunnel syndrome is caused by the compression of the median nerve as it
      transits the carpal tunnel, with an incidence of about 1% of the population. If
      surgery is needed, the treatment involves decompression of the median nerve
      followed sometimes by musculoskeletal outpatient rehabilitation. This paper
      presents a proof-of-concept pilot clinical trial in which the Rutgers Masters II
      haptic glove was tested on five subjects, who were two weeks post-hand surgery.
      Subjects trained for 13 sessions, 30 min per session, three sessions per week,
      and had no conventional outpatient therapy. Computerized measures of performance
      showed group effects in hand mechanical energy (1200% for the virtual ball
      squeezing and DigiKey exercises and 600% for the power putty exercise).
      Improvement in their hand function was also observed (a 38% reduction in virtual
      pegboard errors, and 70% fewer virtual hand ball errors). Clinical strength
      measures showed increases in grip (by up to 150%) and key pinch (up to 46%)
      strength in three of the subjects, while two subjects had decreased strength
      following the study. However, all five subjects improved in their tip pinch
      strength of their affected hand (between 20%-267%). When asked whether they would
      recommend the virtual reality exercises to others, four subjects very strongly
      agreed and one strongly agreed that they would.

PMID- 17436876
TI  - EEG-based synchronized brain-computer interfaces: a model for optimizing the
      number of mental tasks.
AB  - The information-transfer rate (ITR) is commonly used to assess the performance of
      brain-computer interfaces (BCIs). Various studies have shown that the optimal
      number of mental tasks to be used is fairly low, around 3 or 4. We propose an
      experimental validation as well as a formal approach to demonstrate and confirm
      that this optimum is user and BCI design dependent. Even if increasing the number
      of mental tasks to the optimum indeed leads to an increase of the ITR, the gain
      remains small. This might not justify the added complexity in terms of protocol
      design.

PMID- 17436877
TI  - A comparative study on generating training-data for self-paced brain interfaces.
AB  - Direct brain interface (BI) systems provide an alternative communication and
      control solution for individuals with severe motor disabilities, bypassing
      impaired interface pathways. Most BI systems are aimed to be operated by
      individuals with severe disabilities. With these individuals, there is no
      observable indicator of their intent to control or communicate with the BI
      system. In contrast, able-bodied subjects can perform the desired physical
      movements such as finger flexion and one can observe the movement as the
      indicator of intent. Since no external knowledge of intention is available for
      individuals with severe motor disabilities, generating the data for system
      training is problematic. This paper introduces three methods for generating
      training-data for self-paced BI systems and compares their performances with four
      alternative methods of training-data generation. Results of the offline analysis
      on the electroencephalogram data of eight subjects during self-paced BI
      experiments show that two of the proposed methods increase true positive rates
      (at fixed false positive rate of 2%) over that of the four alternative methods
      from 50.8%-58.4% to about 62% which corresponds to 3.6%-11.2% improvement.

PMID- 17436878
TI  - Electrical stimulation of the paralyzed orbicularis oculi in rabbit.
AB  - Dysfunction of the seventh cranial nerve often results in facial paralysis and
      loss of the ability to blink the eye, which can lead to corneal scarring,
      diminished vision, and potential loss of the eye. This study investigated the
      potential of electrical stimulation of the orbicularis oculi muscle as a means of
      restoring blink function. An animal model of orbicularis paralysis was created by
      sectioning the seventh cranial nerve in rabbit. Twenty paralyzed and five normal
      rabbits were acutely implanted with a subcutaneous stimulating electrode near the
      margin of the upper eyelid. Biphasic current controlled stimulation pulses were
      delivered between implanted contacts at the medial and lateral edges of the
      eyelid. Strength-duration curves for lid twitch threshold were generated, and
      quantitative measurements of lid closure were made for systematically varied
      parameters including pulse amplitude, pulse width, number of pulses delivered,
      and duration of paralysis prior to stimulation. Normal rabbits achieved a greater
      degree of lid closure due to electrical stimulation than rabbits that had been
      surgically paralyzed. Of rabbits that had been paralyzed, those demonstrating
      evidence of at least partial reinnervation achieved a greater degree of lid
      closure than those demonstrating persistent denervation. Trains of 10 ms biphasic
      pulses delivered at 50 Hz were found to be the most effective means of eliciting
      lid closure for the range of parameters tested.

PMID- 17436879
TI  - Human nerve stimulation thresholds and selectivity using a multi-contact nerve
      cuff electrode.
AB  - Testing of the recruitment properties and selective activation capabilities of a
      multi-contact spiral nerve cuff electrode was performed intraoperatively in 21
      human subjects. The study was conducted in two phases. An exploratory phase with
      ten subjects gave a preliminary overview of the data and data collection process
      and a systematic phase with eleven subjects provided detailed recruitment
      properties. The mean stimulation threshold of 25 +/- 17 nC was not significantly
      different than previous studies in animal models but much lower than muscle
      electrodes. The selectivity, defined as the percent of total activation of the
      first muscle recruited before another muscle reached threshold, ranged from 27%
      to 97% with a mean of 55%. In each case, the muscle that was selectively
      activated was the first muscle to branch distal to the cuff location. This study
      serves as a preliminary evaluation of nerve cuff electrodes in humans prior to
      chronic implant in subjects with high tetraplegia.

PMID- 17436880
TI  - Methodology and design flow for assisted neural-model implementations in FPGAs.
AB  - Field programmable gate arrays (FPGAs) have previously been shown as high
      performance platforms for neural-modeling applications. Implementations have
      traditionally been time-consuming and error-prone, requiring the neural modeler
      to work outside of their expert domain. This paper demonstrates a new approach to
      the development of neural models using an auto-generation toolkit. This design
      tool enables model construction-level alterations (e.g., adjustment of model
      population size or insertion/deletion of an ionic conductance) within hours and
      parameter changes on-the-fly. The approach is validated on a 40-neuron pre
      Botzinger complex population model consisting of Hodgkin-Huxley style
      conductances and fully interconnected synapses. A total of 1880 parameters are on
      the-fly user tunable on a free-running model. The resulting implemented model
      performs at a theoretical 8.7 x real-time utilizing 90% of logic elements within
      a Xilinx Virtex-4 XC4VSX35-fg676-10 FPGA.

PMID- 17436881
TI  - Stochastic estimation of arm mechanical impedance during robotic stroke
      rehabilitation.
AB  - This paper presents a stochastic method to estimate the multijoint mechanical
      impedance of the human arm suitable for use in a clinical setting, e.g., with
      persons with stroke undergoing robotic rehabilitation for a paralyzed arm. In
      this context, special circumstances such as hypertonicity and tissue atrophy due
      to disuse of the hemiplegic limb must be considered. A low-impedance robot was
      used to bring the upper limb of a stroke patient to a test location, generate
      force perturbations, and measure the resulting motion. Methods were developed to
      compensate for input signal coupling at low frequencies apparently due to human
      machine interaction dynamics. Data was analyzed by spectral procedures that make
      no assumption about model structure. The method was validated by measuring simple
      mechanical hardware and results from a patient's hemiplegic arm are presented.

PMID- 17436882
TI  - Linear summation of torque produced by selective activation of two motor
      fascicles.
AB  - Linear summation of torque was observed while applying selective activation to
      two different motor fascicles in the cat sciatic nerve. The excitatory stimulus
      was applied to two or more contacts housed in a four contact self-sizing spiral
      cuff electrode. To achieve a linear summation of torque, a delay between the two
      stimuli that was longer than the length of the facilitatory period but less than
      the length of the refractory period was used. Using a 900-micros delay between
      pulses, linear summation of two different torque outputs was successfully
      achieved in 125 out of 129 trials across five cats. These trials were performed
      using cuff electrodes that were in place for periods ranging up to 352 days. The
      results of these studies support the hypothesis that a single self-sizing spiral
      cuff with multiple contacts and a single lead may be used in place of several
      muscle-based electrodes each with its own separate lead.

PMID- 17436883
TI  - The optimal controller delay for myoelectric prostheses.
AB  - A tradeoff exists when considering the delay created by multifunctional
      prosthesis controllers. Large controller delays maximize the amount of time
      available for EMG signal collection and analysis (and thus maximize
      classification accuracy); however, large delays also degrade prosthesis
      performance by decreasing the responsiveness of the prosthesis. To elucidate an
      "optimal controller delay" twenty able-bodied subjects performed the Box and
      Block Test using a device called PHABS (prosthetic hand for able bodied
      subjects). Tests were conducted with seven different levels of controller delay
      ranging from nearly 0-300 ms and with two different artificial hand speeds. Based
      on repeted measures ANOVA analysis and a linear mixed effects model, the optimal
      controller delay was found to range between approximately 100 ms for fast
      prehensors and 125 ms for slower prehensors. Furthermore, the linear mixed
      effects model shows that there is a linear degradation in performance with
      increasing delay.

PMID- 17436884
TI  - Graphical tactile displays for visually-impaired people.
AB  - This paper presents an up-to-date survey of graphical tactile displays. These
      devices provide information through the sense of touch. At best, they should
      display both text and graphics (text may be considered a type of graphic). Graphs
      made with shapeable sheets result in bulky items awkward to store and transport;
      their production is expensive and time-consuming and they deteriorate quickly.
      Research is ongoing for a refreshable tactile display that acts as an output
      device for a computer or other information source and can present the information
      in text and graphics. The work in this field has branched into diverse areas,
      from physiological studies to technological aspects and challenges. Moreover,
      interest in these devices is now being shown by other fields such as virtual
      reality, minimally invasive surgery and teleoperation. It is attracting more and
      more people, research and money. Many proposals have been put forward, several of
      them succeeding in the task of presenting tactile information. However, most are
      research prototypes and very expensive to produce commercially. Thus the goal of
      an efficient low-cost tactile display for visually-impaired people has not yet
      been reached.

PMID- 17436885
TI  - Digital emulation of pulse frequency modulation for neuroprosthetic sensory
      feedback.
AB  - Pulse frequency modulation (PFM) is a method of encoding information where the
      instantaneous frequency of a pulse train carries the signal's information. PFM is
      of particular interest to those working towards interfacing prosthetic devices
      directly with the human nervous system. In this paper, we consider the effects of
      directly implementing PFM with a digital microprocessor. We consider three
      digital PFM algorithms: two are deterministic, and the third has a probabilistic
      nature that has desirable time-averaged and ensemble behavior. For each
      algorithm, we analytically bound the error between the desired pulse frequency
      and the actual frequency output by the microprocessor. We aim to provide tools
      for the design and analysis of closed-loop neuroprosthetic systems containing
      PFM.

PMID- 17436886
TI  - An intelligent powered wheelchair to enable mobility of cognitively impaired
      older adults: an anticollision system.
AB  - Older adults with cognitive impairments are generally prohibited from using
      powered wheelchairs, because of the high risk of collisions with people and
      objects. This paper describes and presents the preliminary results of a system
      that uses an infrared sensor to provide anticollision and a prompting system for
      a powered wheelchair that helps guide the user safely past obstacles. Trials with
      the prototyped system detected collisions and stopped the chair in 95% of trials
      with an object and generated no false alarms.

PMID- 17436887
TI  - Force control strategies while driving electric powered wheelchairs with
      isometric and movement-sensing joysticks.
AB  - Innovations to control interfaces for electric powered wheelchairs (EPWs) could
      benefit 220000 current users and over 125000 individuals who desire mobility but
      cannot use a conventional motion sensing joystick (MSJ). We developed a digital
      isometric joystick (IJ) with sophisticated signal processing and two control
      functions. In a prior study, subjects' driving accuracy with our IJ was
      comparable to using an MSJ. However, we observed subjects using excessive force
      on the IJ possibly because its rigid post provides no positional feedback. Thus,
      this paper examines the time-series data recorded in the previous study to
      characterize subjects' force control strategies since weakness is a concern.
      Eleven EPW users with upper limb impairments drove an EPW using an IJ with two
      different control functions and an MSJ in a Fitts' law paradigm. Subjects relied
      upon positional feedback from the MSJ and used appropriate force. In contrast,
      subjects using the IJ with either control function applied significantly higher
      force than necessary (p < 0.0001 and p = 0.0058). Using higher average force was
      correlated with quicker trial times but not associated with accuracy. Lack of
      positional feedback may result in use of excess isometric force. Modifying
      control functions, adjusting gain, or providing additional training or feedback
      might address this problem.

PMID- 17436888
TI  - Will the below-inflation pay deal add to a new recruitment crisis.

PMID- 17436889
TI  - The gang's all here.
AB  - Glugs cartoon characters feature in a handbook and training course to help health
      visitors tackle eating and weight problems in children. The Glugs spread the
      message of eating healthily.

PMID- 17436891
TI  - Home delivery. Interview by Barbara Millar.
AB  - Nurse/paramedic teams act as first responders to some emergency calls and prevent
      unnecessary A&E admissions.

PMID- 17436890
TI  - Blood simple.
AB  - New recommendations are aimed at making blood transfusions safer for patients and
      less complicated for nurses to administer.

PMID- 17436892
TI  - Pathophysiology and classification of stroke.
AB  - There are a wide variety of causes of stroke and as many different forms of
      presentation, depending on the area of the brain affected. This article describes
      how different types of stroke present and outlines the likely outcome for
      patients for each type.

PMID- 17436893
TI  - Improving the numeracy skills of nurse prescribers.
AB  - With the expansion of nurse prescribing to include the whole British National
      Formulary, it is essential that all prescribing nurses can accurately calculate
      and check medication doses. A more uniform approach to professional education for
      nurse prescribers is needed. This process would be assisted by dissemination of
      existing good practice and adjustments to the current national standards of
      assessment.

PMID- 17436894
TI  - Cervical screening in an Orthodox Jewish community.
AB  - This article discusses the possible conflicts of interest in offering cervical
      screening to Orthodox Jewish women. Women in this community are at lower risk of
      cervical intraepithelial neoplasia than the general population and may object to
      screening because of religious reasons. The author suggests that national targets
      should be flexible to accommodate different cultures. Practice nurses can then
      concentrate on providing the most appropriate care for different ethnic
      minorities.

PMID- 17436895
TI  - Fatigue in patients receiving palliative care.
AB  - This article discusses fatigue in patients receiving palliative care. The article
      initially considers the prevalence of fatigue in different groups of palliative
      care patients, then addresses how it manifests before reviewing how it can be
      assessed and managed. The focus of the article is on palliative care but it draws
      on, and has relevance for, chronic disease more widely.

PMID- 17436896
TI  - Obsessive compulsive disorder.

PMID- 17436897
TI  - My turning point.

PMID- 17436898
TI  - Raising a research profile.

PMID- 17436899
TI  - Veterinarians and organic farmers have the same goal.

PMID- 17436900
TI  - An ethicist's commentary on veterinary medicine taking moral stands.

PMID- 17436901
TI  - Keeping up with the Joneses--comparison of fees.

PMID- 17436902
TI  - Status of Porcine circovirus diseases in western Canada.

PMID- 17436903
TI  - Small animal deworming protocols, client education, and veterinarian perception
      of zoonotic parasites in western Canada.
AB  - Questionnaires were mailed to veterinarians in western Canada to determine dog
      and cat deworming protocols and the association between perceived zoonotic risk
      and perceived prevalence of endoparasites and deworming protocols. Of the
      responding veterinarians (545), 13% and 39% recommended deworming protocols
      consistent with established guidelines for puppies and kittens, respectively.
      Mixed animal practitioners and high-perceived prevalence of Toxocara cati were
      associated with increased appropriate kitten deworming (P < 0.01 and P = 0.04,
      respectively). High-perceived zoonotic concern of Toxocara canis was associated
      with increased appropriate puppy deworming (P = 0.01). Sixty-eight percent of
      veterinarians noted an established hospital deworming protocol, although only 78%
      followed the protocol. Forty-four percent of veterinarians stated they discussed
      with all clients the zoonotic risk of animal-derived endoparasites, whereas the
      remainder discussed it only under particular circumstances or not at all. Most
      small animal deworming protocols recommended in western Canada begin too late to
      inhibit endoparasite shedding. Increased educational efforts directed at
      veterinarians are warranted.

PMID- 17436904
TI  - Effects of isoflurane on Tei-index of myocardial performance in healthy dogs.
AB  - Recently, the Tei-index, a noninvasive index that combines systolic and diastolic
      time intervals, has been proposed to assess global cardiac performance. However,
      the effects of isoflurane on the Tei-index have not been characterized. This
      study aimed at studying the effects of 1.0 minimal alveolar concentration
      isoflurane anesthesia on the pre-ejection period (PEP), left ventricular ejection
      time (LVET), PEP/LVET ratio, isovolumic relaxation time (IVRT), stroke index
      (SI), cardiac index (CI), heart rate (HR), and the Tei-index in healthy
      unpremedicated dogs. We observed significant increases in PEP, PEP/LVET ratio,
      IVRT, and TEI, whose maximal increases obtained throughout the study were 47%,
      48%, 78%, and 56%, respectively. The LVET and HR did not change significantly,
      whereas the SI and CI decreased during anesthesia (29% and 26%, respectively). In
      conclusion, isoflurane produced direct effects on the Tei-index. The changes in
      systolic and diastolic parameters were supportive of this finding and were
      consistent with an overall impairment of left ventricular function during
      anesthesia.

PMID- 17436905
TI  - Evaluation of a hand-held lactate analyzer in dogs.
AB  - A hand-held lactate test device and a blood gas auto analyzer were compared. The
      objective of the study was to evaluate the performance of the hand-held device in
      dogs in a clinical setting. Blood lactate levels were evaluated on 30 samples
      from healthy client-owned dogs and 48 samples from client-owned dogs with various
      diseases. A blood sample was collected from each healthy dog by either jugular or
      cephalic venipuncture and from each sick dog from the jugular, cephalic, or
      saphenous vein, or from an arterial catheter if applicable. One and a half
      milliliters of the blood sample was immediately transferred to a heparinized
      vacutainer tube. Enough blood was then drawn from the heparinized tube to allow
      split sample simultaneous analysis with both machines. Samples from the sick dogs
      represented a wide range of clinically relevant lactate values. Good agreement
      between lactate values from both devices was obtained in both sick and healthy
      dogs. Lactate values in the healthy group (< 2.9 mmol/L with the hand-held
      device, < 2.6 mmol/L with the blood gas analyzer) were similar to those
      previously reported (< 2.5 mmol/L). The results of this study support the use of
      the hand-held device in dogs in a clinical setting.

PMID- 17436906
TI  - Identification of normal parameters for ultrasonographic examination of the
      equine large colon and cecum.
AB  - Six healthy horses were examined by using transabdominal ultrasonography, as
      described (1-3), to evaluate activity and size of the large colon and cecum at
      various locations. Using size and number of sacculations, activity patterns and
      contractile frequency; significant differences that would allow ultrasonographic
      identification of dorsal versus ventral colons, if they were displaced, were not
      found. The cecum had significantly greater activity than the colon, and a trend
      was seen towards smaller sacculations in the cecum than in the large colon.

PMID- 17436907
TI  - B-cell lymphoma in a dog with ehrlichiosis (Ehrlichia canis) and systemic
      histoplasmosis (Histoplasma capsulatum).
AB  - A mixed breed dog treated for ehrlichiosis and systemic histoplasmosis developed
      a refractory thrombocytopenia. When an abdominal mass was detected, exploratory
      laparotomy and biopsies confirmed lymphoma, which on immunohistochemical stains
      was determined to be of B-cell origin. Conceivably, the B-cell lymphoma in this
      dog was associated with chronic inflammation from ehrlichiosis, histoplasmosis,
      or both.

PMID- 17436908
TI  - Suspect osteogenesis imperfecta in a male kitten.
AB  - A 4.5-month-old, male domestic shorthair was presented with bilateral femoral
      fractures after falling from a low height. Radiographs revealed reduced radio
      opacity and thin cortices of all long bones. A presumptive diagnosis of
      osteodystrophy, secondary to osteogenesis imperfecta, was made on postmortem
      examination.

PMID- 17436909
TI  - Porcupine quills in raccoons as an indicator of rabies, distemper, or both
      diseases: disease management implications.
AB  - A relationship was detected between the presence of embedded porcupine quills and
      the diagnosis of rabies in raccoons in eastern Canada during 1999-2004. No
      relationship was found between the presence of quills in raccoons and the
      diagnosis of canine distemper. Raccoons with embedded quills should be submitted
      for rabies testing.

PMID- 17436910
TI  - Nasal rhinosporidiosis in a mule.
AB  - A mass was removed from the nostril of a mule that exhibited unilateral epistaxis
      and nasal discharge. Impression smears revealed oval structures consistent with
      spores of Rhinosporidium seeberi. Microscopically, the mass was composed of
      fibrovascular granulomatous tissue containing sporangia R. seeberi. Surgical
      excision and antifungal treatment proved curative.

PMID- 17436911
TI  - Atypical presentation of cutaneous T-cell lymphosarcoma in a 19-month-old
      Holstein heifer.
AB  - A 19-month-old Holstein heifer was presented with bilateral auricular masses.
      Multiple cutaneous masses and prefemoral lymphadenopathy were also found. On post
      mortem, masses affecting internal viscera were observed. The heifer was
      seronegative for Bovine leukemia virus (BLV). The cutaneous form of sporadic
      juvenile lymphosarcoma was diagnosed and determined to be ofT-cell origin.

PMID- 17436913
TI  - Diagnostic ophthalmology ophtalmologie diagnostique. Left internal
      ophthalmoplegia.

PMID- 17436912
TI  - Radiation therapy for pituitary tumors in the dog and cat.

PMID- 17436914
TI  - Secondary hepatogenous photosensitization in a llama (Lama glama) bred in the
      state of Sao Paulo, Brazil.

PMID- 17436915
TI  - Obesity and spine surgery: relation to perioperative complications.
AB  - OBJECT: Many patients undergoing elective thoracic or lumbar fusion procedures
      are obese, but the contribution of obesity to complications in spine surgery has
      not been defined. The authors retrospectively assessed the prevalence of obesity
      in a cohort of patients undergoing thoracic and lumbar fusion and correlate the
      presence of obesity with the incidence of operative complications. METHODS: A
      retrospective review of consecutive patients treated by a single surgeon (J.K.R.)
      over a 36-month period at either Rush University Medical Center or the
      Neurological and Orthopedic Institute of Chicago was performed. The authors
      identified 332 elective thoracic and lumbar spine surgery cases; the cohort was
      restricted to include only patients with symptomatic degenerative conditions in
      need of an anterior, posterior, or combined anterior-posterior fusion. Cases of
      trauma, tumor, and infection and any case in which the procedure was performed
      for emergency indications were excluded. A total of 97 cases were identified; of
      these 86 procedures performed in 84 patients had adequate follow-up material for
      inclusion in the present study. A broad definition of complications was used.
      Complications were divided into adverse events (minor) and significant
      complications (major) based on their impact on patient outcome. Stepwise
      multivariate logistic regression was used to identify which variables had a
      significant effect on the risk of complications. Variables considered were body
      mass index (BMI), height, weight, age, sex, presence or absence of diabetes
      mellitus (DM) and/or hypertension, number of levels fused (single compared with
      multiple), and type of surgery performed. The mean BMI for the cohort was 28.8
      (95% confidence interval 24.4-30.3); 60 patients (71.4%) were considered
      overweight or obese (BMI > or = 25). There were 42 complications in 31 patients
      (36.9%); this included 19 significant complications in 17 patients (20.2%).
      Logistic regression revealed that the probability of a significant complication
      was related to BMI (p < 0.04); the chance of a significant complication was 14%
      with a BMI of 25, 20% with a BMI of 30, and 36% with a BMI of 40. Positioning
      related palsies were only found in extremely obese patients (BMI > or = 40). The
      probability of minor complication occurrence increased with age (p < 0.02), not
      BMI. The rate of complications was independent of sex as well as the presence of
      DM or hypertension. A standard collection of complications occurred, including
      wound infection (three cases), cerebrospinal fluid leakage (eight cases, one
      requiring reoperation), deep vein thrombosis (two cases), cardiac events (four
      cases), symptomatic pseudarthrosis (one case), pneumonia (three cases), prolonged
      intubation (two cases), urological issues (eight cases), positioning-related
      palsy (two cases), and neuropathic pain (two cases). CONCLUSIONS: Obesity is a
      prevalent condition in patients undergoing elective fusion for degenerative
      spinal conditions and may increase the prevalence and incidence of perioperative
      complications. In their analysis, the authors correlated increasing BMI and
      increased risk of significant postoperative complications. The correlation of
      obesity and perioperative complications may assist in the preoperative evaluation
      and selection of patients for surgery.

PMID- 17436916
TI  - Anterior approaches to fusion of the cervical spine: a metaanalysis of fusion
      rates.
AB  - OBJECT: Anterior cervical discectomy (ACD), ACD with interbody fusion (ACDF),
      ACDF with placement of an anterior plate system (ACDFP), corpectomy, and
      corpectomy with plate placement are used to fuse the cervical spine. The authors
      conducted a metaanalysis of studies published after 1990 in which fusion rates
      achieved with each procedure were reported for patients with degenerative disease
      at one, two, and three disc levels. METHODS: Twenty-one papers each included data
      on at least 25 patients. In each of the 21 studies the average clinical follow up
      was more than 12 months, and the results were evaluated according to radiographic
      evidence of fusion and delineated by the number of levels fused. Chi-square and
      Fisher exact tests were used for comparisons. The mean age of the patients was
      46.7 years, 46.6% were female, and the mean follow-up period was 39.6 months. The
      studies included 2682 patients and the overall fusion rate was 89.5%. For single
      disc-level disease, fusion rates were 84.9% for ACD, 92.1% for ACDF, and 97.1%
      for ACDFP (p = 0.0002). For two disc-level disease, fusion rates were 79.9% for
      ACDF, 94.6% for ACDFP, 95.9% for corpectomy, and 92.9% for corpectomy with plate
      placement (p = 0.0001). For three disc-level disease, fusion rates were 65.0% for
      ACDF, 82.5% for ACDFP, 89.8% for corpectomy, and 96.2% for corpectomy with plate
      placement (p = 0.0001). The use of anterior plates significantly improved fusion
      for one-level (p < 0.0001), two-level (p < 0.0001), and three-level (p < 0.05)
      ACDF. There was no significant difference in fusion rates between two-level ACDF
      and corpectomy with plate placement. CONCLUSIONS: The anticipated fusion rate is
      one of several factors that may guide surgical decision making. Anterior cervical
      decompression and fusion results in high fusion rates. The results of the
      authors' study show that regardless of the number of levels fused, the use of an
      anterior cervical plate system significantly increases the fusion rate. For two
      disc-level disease, there was no significant difference between ACD with a plate
      system or corpectomy with a plate system. For three-disc-level disease, however,
      the evidence suggests that corpectomy with plate placement is associated with
      higher fusion rates than discectomy with plate placement.

PMID- 17436917
TI  - Cervical high-intensity intramedullary lesions without spinal cord compression in
      achondroplasia.
AB  - OBJECT: In the authors' experience, the appearance of a cervical high-intensity
      intramedullary (CHII) lesion on magnetic resonance (MR) images in the absence of
      local spinal cord compression is frequently observed in patients with
      achondroplasia, although it has been mentioned only sporadically in the
      literature. Hence, the authors conducted a retrospective study in a consecutive
      single-center series of patients with achondroplasia to determine the prevalence
      and imaging features of this entity. They also reviewed the literature. METHODS:
      Cervical MR imaging studies obtained to establish diagnoses in 25 adult patients
      with achondroplasia and assessed at the Leiden University Medical Center after
      neurogenic claudication developed were evaluated for the presence of a CHII
      lesion. Imaging features of the lesion were described, and a literature search
      was performed. The CHII lesion was demonstrated in 16 of 25 adult patients with
      achondroplasia (64%) in the absence of local spinal cord compression. All lesions
      were located at the C-2 level and appeared to be confined to the gray matter. The
      CHII lesion was associated with local spinal cord thinning, most likely
      representing focal atrophy. In their literature search the authors found no
      description of the CHII lesion in adults, although its presence has been
      mentioned as a peculiarity in the pediatric achondroplastic population.
      CONCLUSIONS: In this large series of adults with achondroplasia and symptomatic
      neurogenic claudication, a CHII lesion was frequently depicted on imaging
      studies, but it remains a fully explored imaging phenomenon. Its cause and
      clinical relevance require investigation, as does its prevalence in the general
      achondroplastic population.

PMID- 17436918
TI  - Significance of the double-layer and single-layer signs in the ossification of
      the posterior longitudinal ligament of the cervical spine.
AB  - OBJECT: The purpose of this study was to elucidate the significance of the signs
      of dural penetration, which were previously described by Hida et al. This goal
      was accomplished by an analysis of preoperative computed tomography scans and a
      review of the medical records of patients who underwent removal of the
      ossification of the posterior longitudinal ligament (OPLL) via the anterior
      approach. METHODS: Outcomes in 197 patients with cervical OPLL who underwent
      anterior decompression and fusion were studied retrospectively. The types of
      OPLL, single- and double-layer signs of dural penetration, diameter of the
      central hypodense mass of the double-layer sign, and the presence of actual dural
      penetration were evaluated. Signs of dural penetration were found in 30.5% of
      patients. These signs were much more prevalent in patients with nonsegmental
      OPLL. Dural defects were present in 20 (52.6%) of 38 patients with double-layer
      signs and in three (13.6%) of 22 patients with single-layer signs. Among patients
      in the double-layer sign group, the mean diameter of the central hypodense masses
      was thicker in the group with an actual dural defect. Although not to the degree
      reported by Hida et al., the double-layer sign had a significant association with
      dural defects. In particular, the thicker the central hypodense mass of the
      double-layer sign, the greater the possibility of a dural defect. However, a
      single-layer sign had less significance than a double-layer one. CONCLUSIONS:
      Surgeons should be alert to the increased possibility of a dural defect when
      there is a double-layer sign with a thick central hypodense mass in nonsegmental
      OPLL.

PMID- 17436919
TI  - Treatment of painful osteoporotic compression and burst fractures using
      kyphoplasty: a prospective observational design.
AB  - OBJECT: The aim of this study was to test the hypothesis that kyphoplasty is an
      effective treatment in painful osteoporotic vertebral fractures, even with
      involvement of the posterior cortical wall. METHODS: Between December 2001 and
      May 2004, 74 consecutive patients were treated with kyphoplasty for 118 painful
      osteoporotic compression (38%) or burst (62%) fractures. Additional decompression
      of the spinal canal was performed in six patients, internal fixation in three.
      Data were collected in a prospective observational design until May 2005. The
      preoperative workup included neuroimaging (plain x-ray films, densitometry, short
      tau inversion recovery magnetic resonance imaging, and computed tomography
      scanning) and clinical parameters (general and neurological examinations, visual
      analog scale [VAS], Karnofsky Performance Scale [KPS], and 36-Item Short Form
      Health Survey [SF]-36). At predefined time intervals (at discharge and 6 weeks
      and 3, 6, 12, and 24 months posttherapy) the patients were evaluated (x-ray
      films, neurological status, VAS, KPS, and SF-36). Kyphoplasty led to a
      significant reduction in kyphotic deformity (mean +/- standard error of the mean,
      sagittal index: preoperative 10 +/- 1 degrees, postoperative 5 +/- 1 degrees),
      and an improvement in pain (VAS: preoperative 70 +/- 3, postoperative 23 +/- 2),
      activity (KPS score: preoperative 51 +/- 3, postoperative 71 +/- 2), and mental
      and physical health (SF-36, mental status: preoperative 43, postoperative 58; SF
      36, physical status: preoperative 24, postoperative 35). No secondary narrowing
      of the spinal canal by the retropulsed posterior wall was observed after the
      procedure. Clinical improvement was durable (mean follow up 15 +/- 1.1 months),
      although the VAS score secondarily increased slightly. All patients, who suffered
      from a compression-induced motor deficit, recovered completely during the follow
      up interval. The main procedural complications consisted of one symptomatic
      extravertebral cement leakage (permanent monoparesis) requiring open revision,
      two nerve root contusions (transient radiculopathy), and one wound infection.
      CONCLUSIONS: Kyphoplasty is effective in the treatment of painful osteoporotic
      vertebral compression and burst fractures, at least under medium-term conditions.
      The potential complication of procedure-related secondary narrowing of the spinal
      canal by the retropulsed posterior wall in burst fractures appears to be more of
      a theoretical than an actual risk.

PMID- 17436920
TI  - Surgical results in patients with tuberculosis of the spine and severe lower
      extremity motor deficits: a retrospective study of 48 patients.
AB  - OBJECT: Significant numbers of patients with spinal tuberculosis (TB), especially
      in developing countries, still present late after disease onset with severe
      neurological deficits. The authors conducted a study to assess the outcome in
      these patients. METHODS: Fifty-nine patients with spinal TB and severe motor
      deficits underwent surgery at the authors' center during the past 10 years. Data
      obtained in 48 patients with a minimum of 3 months of follow up (mean follow-up
      period 12.8 months) were analyzed. The disease in 34 patients was characterized
      by Frankel Grade A/B (Medical Research Council Grade 0/5) and in 14 patients by
      Frankel Grade C (unable to walk even with support) at admission. Thirty (88%) of
      the 34 patients with Frankel Grade A/B status and 13 (92.8%) of the 14 patients
      with Frankel Grade C status at admission experienced improvement to Frankel Grade
      D/E (walking with or without support) at the last follow-up examination 3 or more
      months after surgery. The degree of improvement exhibited by patients with a
      Frankel Grade A/B spinal cord injury was comparable to that shown by patients
      with Frankel Grade C status. Even patients with flaccid paraplegia, gross sensory
      deficit, prolonged weakness, spinal cord signal changes demonstrated on magnetic
      resonance imaging, and bladder involvement have experienced dramatic improvement
      in motor function since surgery. A significant number of the patients have shown
      remarkable improvement in other symptoms such as pain (91.6%), spasticity (88%),
      and bladder symptoms (88%). CONCLUSIONS: A significant proportion of patients
      with spinal TB and severe motor deficits experience remarkable improvement after
      surgical decompression and hence should undergo surgery even though they may be
      suffering from paraplegia of considerable duration.

PMID- 17436921
TI  - Effective prevention of surgical site infection using a Centers for Disease
      Control and Prevention guideline-based antimicrobial prophylaxis in lumbar spine
      surgery.
AB  - OBJECT: Antimicrobial prophylaxis (AMP) reduces the rate of surgical site
      infection (SSI) in lumbar spine surgery, but a great deal of variation exists
      regarding the timing and duration of AMP. The authors had previously used
      prophylactic antibiotics for 5 to 7 postoperative days. Based on the Centers for
      Disease Control and Prevention (CDC) guideline, the AMP period was changed to the
      day of surgery only. In the current study, the authors compared the rate of SSI
      in lumbar spine surgeries between two different protocols of AMP. METHODS: Data
      from 1597 consecutive uninfected patients who had undergone lumbar spine surgery
      between January 1999 and September 2004 were reviewed. The pathophysiologies
      among these patients included disc herniation in 686, degenerative
      spondylolisthesis in 340, spinal stenosis in 259, failed lumbar surgeries in 73,
      degenerative scoliosis in 52, isthmic spondylolisthesis in 48, spinal trauma in
      34, foraminal stenosis in 27, spinal tumor in 27, and miscellaneous in 51
      patients. The rate of SSI was compared between the two AMP groups. There were
      1133 patients in the multiple-dose group, and 464 patients in the single-dose
      group. The rate of instrumentation surgery was not statistically different
      between the multiple-dose group (43%) and the single-dose group (39%). The
      overall rate of SSI was 0.7%. The SSI rate was 0.8% in the multiple-dose group
      and 0.4% in the single-dose group; the difference between the two was not
      significant. Regarding the organisms of SSI, resistant strains of bacteria were
      cultured in five (83.3%) of six patients in the multiple-dose group, whereas none
      was cultured in the single-dose group. CONCLUSIONS: Data in the current study did
      not demonstrate a difference in the rate of SSI between the two different AMP
      protocols. Based on the CDC guideline, a single dose of AMP was proven to be
      efficacious for the prevention of SSI in lumbar spine surgeries. A shorter
      duration of first-generation cephalosporin use may effectively prevent the
      emergence of antibiotic-resistant bacterial infection.

PMID- 17436922
TI  - Clinical outcomes and complications after pedicle subtraction osteotomy for
      correction of thoracolumbar kyphosis.
AB  - OBJECT: Many patient complications have been reported after the use of the
      pedicle subtraction osteotomy (PSO) technique. To the authors' knowledge, no
      previous reseachers have reported on the causes of complications after using the
      single-stage PSO technique with a posterior approach. The purpose of this study
      was to investigate complications after the procedure, to clarify the factors
      influencing the complications, and to identify ways to minimize complications.
      METHODS: Records for 67 patients treated with the PSO technique were examined
      retrospectively. All complications were recorded and analyzed in relation to the
      radiological and clinical outcomes. No patient died or became paraplegic as a
      result of surgery. There were 48 surgery-related complications in 27 patients
      (40%): six intraoperative, four perioperative, and 38 late-onset postoperative
      complications. As the study progressed and more patients were treated, the rate
      of intraoperative complications decreased significantly. The incidence of late
      onset complications associated with an adjacent-segment progression of kyphosis
      was lower in patients with a long fusion from a midthoracic vertebra to the
      sacrum or pelvis than in patients treated with a shorter fusion. The C-7 plumb
      line values and postoperative complications were closely correlated with clinical
      results. CONCLUSIONS: Intraoperative complications can be prevented or the risks
      minimized with adequate surgical training. Most of the late-onset complications
      in these patients were related to the progression of kyphosis. The frequency of
      complications was closely correlated with patient satisfaction at follow up.
      Correcting the C-7 plumb line value with minimal complications appeared to lead
      to better clinical results.

PMID- 17436923
TI  - Inhibition of x-irradiation-enhanced locomotor recovery after spinal cord injury
      by hyperbaric oxygen or the antioxidant nitroxide tempol.
AB  - OBJECT: Hyperbaric oxygen (HBO), the nitroxide antioxidant tempol, and x
      irradiation have been used to promote locomotor recovery in experimental models
      of spinal cord injury. The authors used x-irradiation of the injury site together
      with either HBO or tempol to determine whether combined therapy offers greater
      benefit to rats. METHODS: Contusion injury was produced with a weight-drop device
      in rats at the T-10 level, and recovery was determined using the 21-point Basso
      Beattie-Bresnahan (BBB) locomotor scale. Locomotor function recovered
      progressively during the 6-week postinjury observation period and was
      significantly greater after x-irradiation (20 Gy) of the injury site or treatment
      with tempol (275 mg/kg intraperitoneally) than in untreated rats (final BBB
      Scores 10.6 [x-irradiation treated] and 9.1 [tempol treated] compared with 6.4
      [untreated], p < 0.05). Recovery was not significantly improved by HBO (2 atm for
      1 hour [BBB Score 8.2, p > 0.05]). Interestingly, the improved recovery of
      locomotor function after x-irradiation, in contrast with antiproliferative
      radiotherapy for neoplasia, was inhibited when used together with either HBO or
      tempol (BBB Scores 8.2 and 8.3, respectively). The ability of tempol to block
      enhanced locomotor recovery by x-irradiation was accompanied by prevention of
      alopecia at the irradiation site. The extent of locomotor recovery following
      treatment with tempol, HBO, and x-irradiation correlated with measurements of
      spared spinal cord tissue at the contusion epicenter. CONCLUSIONS: These results
      suggest that these treatments, when used alone, can activate neuroprotective
      mechanisms but, in combination, may result in neurotoxicity.

PMID- 17436924
TI  - Identical twins with cervical myelopathy: a case for hereditary cervical
      spondylosis? Report of two cases and review of the literature.
AB  - Although degenerative cervical spondylosis is a common neurosurgical problem, not
      much has been published about the hereditary factors responsible for it. The
      authors report on a set of identical twins who presented to their service at a
      relatively young age with myelopathy due to degenerative cervical disc prolapse
      and who needed surgery. The early age of presentation and the fact that the
      patients were identical twins suggest a genetic element. The authors also review
      the available literature on the genetic factors in the causation of degenerative
      cervical spondylosis. To the best of their knowledge this is the first reported
      instance of identical twins with cervical myelopathy at a young age needing
      curative surgery.

PMID- 17436925
TI  - Intramedullary abscess in association with tumor at the conus medullaris. Report
      of two cases.
AB  - The authors report on two patients with intramedullary tumors complicated by
      abscess formation. Both patients experienced abrupt onset of neurological
      deterioration and poor surgical outcome. An intratumoral abscess developed in
      one, whereas the other had a tumor-associated syrinx in which an intramedullary
      abscess developed. Such a conversion of a syrinx into an abscess has not been
      reported earlier. It is septicemia that underlies all such catastrophic
      complications; therefore, rapid neurological deterioration should always be
      looked on with caution and investigated with contrast-enhanced magnetic resonance
      imaging. Despite poor neurological outcome in such patients, urgent surgical
      intervention is mandatory.

PMID- 17436926
TI  - Cervical stenosis, spinal cord neurapraxia, and the professional athlete.

PMID- 17436927
TI  - Cervical neurapraxia in elite athletes: evaluation and surgical treatment. Report
      of five cases.
AB  - OBJECT: Neurapraxia, transient posttraumatic paralysis of the motor and/or
      sensory tracts in the spinal cord, may be a career-ending event in an athlete.
      Management, rehabilitation, and return-to-play decisions remain controversial.
      METHODS: Five elite football players were evaluated after experiencing episodes
      of neurapraxia. All patients experienced bilateral paresthesias--three in all
      four extremities and two in the upper extremities--lasting a few minutes to more
      than 24 hours. Transient motor deficits occurred in two individuals but caused no
      permanent sequelae. Neuroimaging confirmed the presence of herniated discs, focal
      cord compression, and no parenchymal changes in all cases. All patients underwent
      anterior cervical microdiscectomy and fusion, and cervical plates were placed in
      four. After aggressive rehabilitation and confirmation of fusion ranging from 9
      weeks to 8 months postoperatively, the players were allowed to return to active
      play. Two of the players developed recurrent career-ending disc herniations, one
      above and the other below the fusion level. One player required repeated spinal
      cord decompression. CONCLUSIONS: Neurologically intact athletes with focal cord
      compression due to a single-level herniated disc may safely return to football
      after undergoing decompressive surgery and confirmation of fusion. It appears,
      however, that there may be an increased chance of repeated herniation above or
      below a fused level.

PMID- 17436928
TI  - Spinal cord glioblastoma multiforme induced by radiation after treatment for
      Hodgkin disease. Case report.
AB  - The authors report on a 26-year-old man with a very rare case of radiation
      induced intramedullary spinal cord glioblastoma multiforme, which developed
      several years after radiotherapy for Hodgkin disease.

PMID- 17436929
TI  - A novel approach to sagittal balance restoration following iatrogenic sacral
      fracture and resulting sacral kyphotic deformity. Technical note.
AB  - The authors describe the use of sacral pedicle subtraction osteotomy (PSO) with
      multiple sacral alar osteotomies for the correction of sacral kyphosis and pelvic
      incidence and for achieving sagittal balance correction in cases of fixed
      sagittal deformity after a sacral fracture. In this paper, the authors report on
      a novel technique using a series of sacral osteotomies and a sacral PSO to
      correct a fixed sagittal deformity in a patient with a sacral fracture that had
      healed in a kyphotic position. The patient sustained this fracture after a
      previous surgery for multilevel instrumented fusion. Preoperative and
      postoperative radiographic studies are reviewed and the clinical course and
      outcome are presented. Experts agree that the pelvic incidence is a fixed
      parameter that dictates the morphological characteristics of the pelvis and
      affects spinopelvic orientation and sagittal spinal alignment. An increased
      pelvic incidence is associated with a higher degree of spondylolisthesis in the
      lumbosacral junction, and increased shear forces across this junction. The
      authors demonstrate that the pelvic incidence can be altered and corrected with a
      series of sacral osteotomies to improve sacral kyphosis, compensatory lumbar
      hyperlordosis, and sagittal balance.

PMID- 17436930
TI  - Flat arrangement of the cauda equina in Chiari malformation. Case illustration.

PMID- 17436931
TI  - Direct anterolateral balloon kyphoplasty for a painful C-2 osteolytic malignant
      lesion. Case illustration.

PMID- 17436932
TI  - Titanium cervical cage.

PMID- 17436933
TI  - Thoracic myelopathy.

PMID- 17436934
TI  - Bone morphogenetic protein and fusion.

PMID- 17436935
TI  - Effects of aestivation and starvation on the neutral lipid and phospholipid
      content of Biomphalaria glabrata infected with Schistosoma mansoni.
AB  - The effects of aestivation or starvation on the neutral lipid and phospholipid
      content of Biomphalaria glabrata patently infected with Schistosoma mansoni were
      determined by high-performance thin-layer chromatography-densitometry. Infected
      aestivated snails were maintained in a moist chamber at 24 +/- 1 C and a relative
      humidity of 98 +/- 1%. Infected-starved snails were maintained in artificial
      spring water (ASW) at 23 +/- 1 C without exogenous food. Infected snails (the
      controls) were maintained in ASW at 23 +/- 1 C and fed lettuce ad libitum. The 3
      groups were maintained in the laboratory for 7 days, and then the lipids from the
      digestive gland-gonad complex (DGG) were extracted and analyzed by class.
      Infected-aestivated snails exhibited greater mortality rate and weight loss after
      7 days than did the infected-starved snails. The steryl ester concentration in
      the infected-starved snails was significantly increased (P = 0.010) compared with
      the controls but not compared with infected-aestivated snails; the concentration
      of phosphatidylcholine in infected-aestivated snails was significantly decreased
      (P = 0.007) compared with the controls but not when compared with the infected
      starved snails. Aestivation or starvation had a significant effect on the
      concentration of certain lipid classes in the DGG of B. glabrata infected with S.
      mansoni.

PMID- 17436936
TI  - Comparison of microthrix ultrastructure and morphology on the plerocercoid and
      adult scolex of Calliobothrium cf. verticillatum (Tetraphyllidea:
      Onchobothriidae).
AB  - The distal bothridial surfaces of adult triloculate onchobothriids are covered
      with short structures that have been tentatively classified as very short
      filitriches, but this hypothesis has never been tested. Scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM) were used to
      investigate microthrix morphology in the plerocercoid and adult forms of
      Calliobothrium cf. verticillatum, a triloculate onchobothriid tapeworm from Long
      Island Sound (Connecticut). Plerocercoids of C. cf. verticillatum were collected
      from the anterior midgut ceaca of Pagurus pollicaris Say, 1817 (flat-clawed
      hermit crab), and adults were collected from the spiral intestine of the dusky
      smooth hound Mustelis canis (Mitchell, 1815). Two plerocercoids and 2 adults were
      examined using SEM; 2 plerocercoids and 2 adults were examined using TEM.
      Microthrix distribution and morphology (including measurements of total length,
      base length, shaft length, and base width) were investigated on all surfaces of
      the plerocercoid and adult scolex. Slender filitriches and large bladelike
      spinitriches were observed extending from the tegument of plerocercoid and adult
      forms. The filitriches were found to have significantly narrower bases than the
      spinitriches (65-167 nm vs. 466-1,936 nm, respectively). The scolex proper of the
      plerocercoid and adult forms were found to have filitriches of medium-length and
      bladelike spinitriches. The distal bothridial surfaces differed dramatically in
      microthrix morphology between plerocercoid and adult forms; on the distal
      surfaces of the plerocercoids were long filitriches and bladelike spinitriches.
      However, the distal surfaces of the adults had short structures (previously
      hypothesized to be short filitriches) and a few bladelike spinitriches. Serial
      transverse sections revealed that the short structures on the distal bothridial
      surfaces of the adults were homologous with filitriches. They included all of the
      structural components of a filithrix as well as a base width that conformed to
      the filitriches found on other surfaces. The bothridial margins of the
      plerocercoid and adult forms had a microthrix pattern similar to that seen on the
      proximal bothridial surfaces except that the filitriches on the margins were
      significantly longer than those found anywhere else on the bothridia. The most
      dramatic difference between the plerocercoid and adult forms occurred on the
      distal bothridial surfaces, where the filitriches of the adult cestodes were
      significantly shorter and narrower, and the spinitriches were almost entirely
      lacking.

PMID- 17436937
TI  - Household risk factors for Trypanosoma cruzi seropositivity in two geographic
      regions of Ecuador.
AB  - Few studies on the relationship between environmental factors and Trypanosoma
      cruzi transmission have been conducted in Ecuador. We conducted a cross-sectional
      study of household risk factors for T. cruzi seropositivity in 2 distinct
      geographical regions of Ecuador. Exposure information was collected via household
      surveys, and subjects were tested for serological evidence of T. cruzi infection.
      In total, 3,286 subjects from 997 households were included. In the coastal
      region, factors associated with seropositivity were living in a house with a palm
      roof (odds ratio [OR] = 2.63, 95% confidence interval, [1.61. 4.27]), wood walls
      (OR = 5.75 [2.04, 16.18]), or cane walls (OR = 2.81 11.31, 6.04]), and the
      presence of firewood in the peridomicile (OR = 2.48 [1.54, 4.01]). Accumulation
      of trash outside the home was associated with a reduced risk of seropositivity
      (OR = 0.25 [0.12, 0.51]). In the Andean region, living in a house with adobe
      walls was the only factor predictive of T. cruzi seropositivity. In conclusion,
      risk factors for T. cruzi transmission in Ecuador varied by geographic region,
      probably because of differing behavior of the triatomine vector species in each
      region. An understanding of the transmission dynamics of T. cruzi in a particular
      area is necessary for the development of effective Chagas disease control
      strategies in those areas.

PMID- 17436938
TI  - Structure of the parasite communities of a coral reef fish assemblage (Labridae):
      testing ecological and phylogenetic host factors.
AB  - The role of ecological and phylogenetic processes is fundamental to understanding
      how parasite communities are structured. However, for coral reef fishes, such
      information is almost nonexistent. In this study, we analyzed the structure of
      the parasite communities based on composition, richness, abundance, and biovolume
      of ecto- and endoparasites of 14 wrasse species (Labridae) from Lizard Island,
      Great Barrier Reef, Australia. We determine whether the structure of the parasite
      communities from these fishes was related to ecological characteristics (body
      size, abundance, swimming ability, and diet) and/or the phylogenetic relatedness
      of the hosts. We examined 264 fishes from which almost 37,000 individual
      parasites and 98 parasite categories (types and species) were recorded. Gnathiid
      and cestode larvae were the most prevalent and abundant parasites in most fishes.
      Mean richness, abundance, and biovolume of ectoparasites per fish species were
      positively correlated with host body size only after controlling for the host
      phylogeny, whereas no such correlation was found for endoparasites with any host
      variable. Because most ectoparasites have direct transmission, one possible
      explanation for this pattern is that increased space (host body size) may
      increase the colonization and recruitment of ectoparasites. However,
      endoparasites generally have indirect transmission that can be affected by many
      other variables, such as number of prey infected and rate of parasite
      transmission.

PMID- 17436939
TI  - New genus and species of eudactylinid (Siphonostomatoida: Copepoda) from gill
      lamellae of ornate eagle rays, Aetomylaeus vespertilio (Myliobatidae), collected
      in the Beagle Gulf off northern Australia.
AB  - Janinecaira darkthread n. gen., n. sp. (Eudactylinidae, Siphonostomatoida,
      Copepoda) infects gills of the ornate eagle ray Aetomylaeus vespertilio (Bleeker,
      1852) (Myliobatidae, Myliobatiformes) in the Beagle Gulf (Timor Sea, eastern
      Indian Ocean) off northern Australia. The adult female of Janinecaira darkthread
      n. sp. is most easily distinguished from other eudactylinids (Eudactylinidae) by
      its long genital complex that comprises about 86-90% of the total body length. A
      diagnostic key to genera of Eudactylinidae based on adult females is provided.

PMID- 17436940
TI  - Dactylogyrids (Monogenoidea) parasitizing the gills of spinefoots (Teleostei:
      Siganidae): proposal of Glyphidohaptor n. gen., with two new species from the
      Great Barrier Reef, Australia, and G. plectocirra n. comb. from Ras Mohammed
      National Park, Egypt.
AB  - Nine species of Siganus (Perciformes: Siganidae) were examined for dactylogyrids
      (Monogenoidea) from the Red Sea, Egypt; the Great Barrier Reef, Australia; and
      the South China Sea, China. Species of Tetrancistrum were found on siganids from
      all 3 localities; Pseudohaliotrema spp. were restricted to siganids from the
      Great Barrier Reef; and species representing Glyphidohaptor n. gen. were found on
      siganids from the Red Sea and Great Barrier Reef. Siganus argenteus from the Red
      Sea and Siganus vulpinus from the Great Barrier Reef were negative for
      dactylogyrid parasites. Glyphidohaptor n. gen. is proposed for 3 species (2
      species new to science) and the new species are described: Glyphidohaptor
      phractophallus n. sp. from Siganus fuscescens from the Great Barrier Reef;
      Glyphidohaptor sigani n. sp. from Siganus doliatus (type host), Siganus
      punctatus, Siganus corallinus, and Siganus lineatus from the Great Barrier Reef;
      and Glyphidohaptor plectocirra (Paperna, 1972) n. comb. (= Pseudohaliotrema
      plectocirra Paperna, 1972) from Siganus luridus and Siganus rivulatus from the
      Red Sea.

PMID- 17436941
TI  - Epifaunistic arthropod parasites of the four-striped mouse, Rhabdomys pumilio, in
      the Western Cape Province, South Africa.
AB  - Flea, lice, mite, and tick species associated with 510 Rhabdomys pumilio were
      collected at 9 localities in the Western Cape Province, South Africa. The aims of
      the study were first to quantify the species richness, prevalence, and relative
      mean intensity of infestation of epifaunistic arthropod species associated with
      R. pumilio, and second to determine temporal variations in the mean abundance of
      the parasitic arthropods. Each mouse was examined under a stereoscopic microscope
      and its parasites were removed, identified, and quantified. The epifaunal
      population was made up of more than 25,000 individuals and included 8 flea, 1
      sucking louse, 11 mite, and 13 ixodid tick species. Female-biased sex ratios were
      noted for 9 (30%) of the ectoparasite species. Three undescribed mite and 1
      undescribed tick species were recovered, and new locality records for 2 flea, the
      louse, and 2 mite species were documented. A phoretic host association between a
      nonparasitic mite species, Psylloglyphus uilenbergi kivuensis, and 3 flea
      species, Chiastopsylla rossi, Hypsophthalmus temporis, and Listropsylla
      agrippinae, was recorded. The mean abundance of the parasitic mite and insect
      species were higher during the cold wet season, whereas ticks were more numerous
      during the warm dry months. The large number of ectoparasite species on R.
      pumilio, a locally abundant and regionally widespread species, is of medical and
      veterinary importance particularly in relation to the transmission of pathogens
      such as Anaplasma marginale, Babesia caballi, and Babesia canis to domestic
      animals; Rickettsia conori; Yersinia pestis; and the viral disease Crimean-Congo
      hemorrhagic fever to humans.

PMID- 17436942
TI  - Diverse and atypical genotypes identified in Toxoplasma gondii from dogs in Sao
      Paulo, Brazil.
AB  - The prevalence of Toxoplasma gondii in 118 unwanted dogs from Sao Paulo City, Sao
      Paulo State, Brazil, was determined. Antibodies to T. gondii were assayed by the
      modified agglutination test and found in 42 (35.8%) dogs, with titers of 1:20 in
      10, 1:40 in 6, 1:80 in 5, 1:160 in 5, 1:320 in 6, 1:640 in 7, and 1:1,280 or
      higher in 3. Hearts and brains of 36 seropositive dogs were bioassayed in mice,
      or cats, or both. Tissues from 20 seropositive dogs were fed to 20 T. gondii-free
      cats. Feces of cats were examined for oocysts. Toxoplasma gondii was isolated
      from 15 dogs by a bioassay in mice, from the brain alone of 1, from the heart
      alone of 4, and from both brains and hearts of 10. All infected mice from 5 of 15
      isolates died of toxoplasmosis during primary infection. Four additional isolates
      were obtained by bioassay in cats. Genotyping of these 19 T. gondii isolates
      using polymorphisms at 10 nuclear markers including SAG1, SAG2, SAG3, BTUB, GRA6,
      c22-8, c29-2, L358, PK1, and a new SAG2 (an apicoplast marker Apico) revealed 12
      genotypes. One isolate had Type III alleles at all 11 loci, and the remaining 18
      isolates contained a combination of different alleles and were divided into 11
      genotypes. The absence of Type II in Brazil was confirmed. The result supports
      previous findings that T. gondii population genetics is highly diverse in Brazil.

PMID- 17436943
TI  - The use of MM3 monoclonal antibodies for the early immunodiagnosis of ovine
      fascioliasis.
AB  - This study reports a new capture ELISA (MM3-SERO) for the serodiagnosis of sheep
      fascioliasis, based on the use of the monoclonal antibody (mAb) MM3. Like our
      previously reported indirect ELISA method, based on the use of a FPLC-purified
      fraction (fraction IV) of the Fasciola hepatica excretion/secretion antigens
      (ESAs), this new test was able to detect animals infected with very small numbers
      of metacercariae (5-40) and showed no cross-reaction with sera from sheep
      infected with other parasites, i.e., Moniezia spp., Cysticercus tenuicollis, and
      Dicrocoelium dendriticum. In contrast with these 2 methods, some sera (mainly
      those obtained from animals infected with D. dendriticum) showed high
      reactivities in indirect ELISA with whole F. hepatica ESAs used as control.
      Interestingly, the MM3-SERO ELISA has a better signal-to-noise ratio than the
      fraction-IV ELISA, thus allowing detection of seroconversion in infected sheep on
      average 1 wk earlier (3.2 +/- 0.4 wk postinfection [PI] for MM3-SERO ELISA vs.
      4.2 +/- 0.9 wk PI for fraction IV ELISA). Moreover, the antibody response
      detected with MM3-SERO ELISA was more uniform, with seroconversion always
      occurring at 4 wk PI in sheep with 1-2 flukes and at 3 wk PI in sheep with more
      than 2 flukes. The MM3-SERO ELISA was also used to evaluate the kinetics of
      antibody response against MM3-recognized antigens in sera from sheep
      experimentally infected with F. hepatica and then treated with triclabendazole.
      Our results showed that antibody levels dropped by about 25% during the 4-wk
      observation period following the flukicide treatment, whereas they remained
      invariably high in all sheep left untreated. We conclude that the MM3-SERO ELISA
      is a 100% sensitive and 100% specific test for the early serodiagnosis of sheep
      fascioliasis. Preliminary studies in our laboratory seem to indicate that this
      method may also be useful for the determination of anti-F. hepatica antibodies in
      serum and milk of other ruminants. A commercial version of MM3-SERO is currently
      available from BIO X Diagnostics (La Jemelle, Belgium).

PMID- 17436944
TI  - Prevalence of the bopyrid isopod Probopyrus pandalicola in the grass shrimp,
      Palaemonetes pugio, in four tidal creeks on the South Carolina-Georgia coast.
AB  - The grass shrimp, Palaemonetes pugio, is an important food source for many
      invertebrate and fish species, including several of commercial importance. The
      bopyrid Probopyrus pandalicola prevents reproduction in P. pugio by sexual
      sterilization. The purpose of our research was to determine bopyrid prevalence in
      grass shrimp over the course of a year. Shrimp were collected from 2 estuarine
      systems in South Carolina and 2 estuarine systems in Georgia and examined for
      parasite presence, sex, and gravidity. Site-specific monthly prevalence ranged
      from 0 to 6.3%. Country Club Creek had the maximum mean +/- SE prevalence of 3.1
      +/- 0.3%, and Harbour Town had the minimum of 1.3 +/- 0.3%. Maximum prevalence
      was concurrent with peak gravidity for Moon River; thus, at this site the
      negative effect of this parasite on reproductive output may be greater. Reduced
      egg production may affect grass shrimp abundance and ultimately the recruitment
      success of its predators.

PMID- 17436945
TI  - Distribution and habitat characteristics of Manayunkia speciosa and infection
      prevalence with the parasite Ceratomyxa shasta in the Klamath River, Oregon
      California.
AB  - A survey for Manayunkia speciosa, the freshwater polychaete host for the myxozoan
      parasite Ceratomyxa shasta, was conducted from 2003 to 2005 as part of an
      integrated study of the epizootiology of ceratomyxosis in Klamath River
      salmonids. Substrata samples (n = 257) were collected in a variety of habitats
      from Klamath Lake to the mouth of the Klamath River to document occurrence and
      relative abundance of the polychaete by habitat type and to estimate the
      prevalence of C. shasta within selected polychaete populations. Populations of M.
      specios a were identified throughout the Klamath River within pools (51.6%), eddy
      pools (47.0%), and runs (40.0%). Large populations of M. speciosa were
      consistently found at the inflow to the main-stem reservoirs where densities were
      correlated with distance from the inflow into the reservoir. Using polymerase
      chain reaction assay and composite samples, 12 of 71 populations identified were
      tested for C. shasta, revealing a mean infection prevalence of 0.27%. An area of
      elevated infection prevalence (4.9 and 8.3%) was identified with 2 populations
      below a barrier to salmonid migration, which explains the high infectious spore
      densities demonstrated in concurrent studies and observations of C. shasta
      induced mortality in Klamath River fall Chinook salmon (Oncorhynchus
      tshawytscha).

PMID- 17436946
TI  - Klossiella quimrensis (Apicomplexa: Klossiellidae) causes renal coccidiosis in
      western barred bandicoots Perameles bougainville (Marsupialia: Peramelidae) in
      Western Australia.
AB  - Previous studies have described a range of Klossiella species parasitic in
      marsupial hosts. Klossiella quimrensis is the etiologic agent of renal
      coccidiosis in the peramelid marsupial hosts Isoodon obesulus and Perameles
      gunnii in Eastern Australia, but there is no previous report of klossiellosis in
      Western Australian peramelids. This study describes klossiellosis diagnosed by
      histology of renal tissue sections collected during necropsy of 20 Perameles
      bougainville between 2000 and 2005. Sporonts, sporoblasts, and macrogametes were
      identified within parasitophorous vacuoles of epithelial cells located near the
      renal corticomedullary junction. The prevalence of renal coccidiosis in P.
      bougainville diagnosed by renal histology is estimated at 30%. Only a single
      unsporulated sporocyst was detected by examination of cystocentesis-collected
      urine, indicating that microscopic evaluation of urine samples is an insensitive
      diagnostic test for detection of K. quimrensis in P. bougainville. This infection
      in P. bougainville is indirectly associated with mild multifocal interstitial
      lymphohistiocytic nephritis and is likely to be only minimally pathogenic in
      otherwise healthy individuals. Our study also extends the host and geographic
      range of K. quimrensis to include P. bougainville and Western Australia.

PMID- 17436947
TI  - Trypanosoma cruzi prevalence and epidemiologic trends in lemurs on St. Catherines
      Island, Georgia.
AB  - Lemurs on St. Catherines Island, Georgia were tested for Trypanosoma cruzi
      infection to develop a better understanding of the epizootiology of the parasite
      in nonhuman primates in the southeastern United States. Fifty-six ring-tailed
      (Lemur catta), blue-eyed black (Eulemur macaco flavifrons), and black-and-white
      ruffed (Varecia variegata variegata) lemurs were tested by hemoculture and
      serology to determine the prevalence of T. cruzi in the population. Of those
      tested 3 (5%) were identified as culture positive and 25 (44.6%) as seropositive.
      When hemoculture results were compared with those from a similar study performed
      in 1997, prevalence remained unchanged. Genetic characterization of the 3 culture
      isolates indicated they belong to the T. cruzi IIa group, which is identical to
      strains previously isolated from raccoons on the island. Despite the occurrence
      of T. cruzi in the population, there was no evidence that the health of the
      lemurs was compromised as a result of infection. Based upon prevalence and
      available breeding records we speculate that both vertical and vector-mediated
      transmission play significant roles in the epidemiology of T. cruzi on the
      island. This also represents the first report of autochthonous infection in blue
      eyed black and black-and-white ruffed lemurs.

PMID- 17436948
TI  - Molecular characterization of two myoglobins of Paragonimus westermani.
AB  - Myoglobins (Mbs), globin proteins, are present in high concentrations in
      trematodes. In Paragonimus westermani, 2 cDNAs were found to encode Mbs. The
      first clone, Pwmyo1, codes a total of 149 amino acids with a calculated mass of
      16.6 kDa. The second, Pwmyo2, encodes a 146-amino acid protein with a calculated
      mass of 16.2 kDa. The predicted secondary structures showed the presence of 8
      helices, which is the basic characteristic of Mbs. Sequence alignment revealed a
      high homology with the other trematode Mbs. The 2 clones contained the
      characteristic tyrosyl residues at helical positions B10 and distal E7, which are
      substitutions that have been previously shown to contribute to the high oxygen
      affinity of Mbs. Polyclonal antibodies against the recombinant Mbs were raised
      with no cross-reactivity observed. Immunolocalization revealed the proteins to be
      distributed generally throughout the parenchymal tissues, but absent from the
      tegument and reproductive organs. The cell mass of the eggs of the worm stained
      positive to Pwmyo2 but not Pwmyo1, suggesting the stage-specific expression of
      these Mbs.

PMID- 17436949
TI  - Epizootiology of Myxobolus cerebralis, the causative agent of salmonid whirling
      disease in the Rock Creek drainage of west-central Montana.
AB  - Whirling disease, caused by the myxozoan parasite Myxobolus cerebralis, remains a
      health threat to salmonid fish in the western United States. Although various
      aspects of this host-parasite system have been studied, investigations examining
      the overall epizootiology of whirling disease in an ecosystem are lacking.
      Therefore, in June 1998, studies were initiated in the Rock Creek watershed of
      west-central Montana and continued through 2003 to assess the intensity of
      infection in trout using sentinel cages stationed throughout the drainage.
      Additional studies determined the percentage of the annelid worm, Tubifex
      tubifex, releasing M. cerebralis at various localities in Rock Creek and whether
      there was a seasonal or daily periodicity in the release of the triactinomyxon
      stage of the parasite from T. tubifex. Lastly, habitat and water quality
      parameters, and the effects of habitat restoration on transmission of M.
      cerebralis, were assessed. Overall, the intensity of M. cerebralis infections in
      sentinel trout increased significantly throughout the drainage between June of
      1998 and 2003, with the biggest jump occurring between 1998 and 1999. In
      addition, the range of M. cerebralis expanded considerably over the period of
      study. There was no strict correlation between habitat condition and the
      occurrence of the parasite; fish became heavily infected in optimal and marginal
      habitats. However, fish exposed at a locality that had the lowest habitat ranking
      consistently had the highest intensity of infection. The parasite has apparently
      caused a dramatic decline in rainbow trout densities, but the brown trout
      population numbers have increased, and the overall fish density remains high.
      Although a major habitat restoration project did not seem to have an effect on
      decreasing disease intensity, this was not surprising because the restored area
      was located just downstream from a "hotspot" of infected T. tubifex.

PMID- 17436950
TI  - A new oligacanthorhynchid acanthocephalan described from the great horned owl,
      Bubo virginianus (Strigidae), and red-tailed hawk, Buteo jamaicensis
      (Accipitridae), from central Arizona, U.S.A.
AB  - Oligacanthorhynchus nickoli n. sp. (Acanthocephala: Oligacanthorhynchidae) is
      described from the great-horned owl, Bubo virginianus (Gmelin, 1788) (type host),
      and red-tailed hawk, Buteojamaicensis (Gmelin, 1788), collected in central
      Arizona. The new species is most similar to Oligacanthorhynchus iheringi and
      Oligacanthorhynchus minor, but it differs from all congeners primarily by trunk
      length, proboscis size and armature, egg size, geographical range, and host
      species. It is distinguished from the 9 Oligacanthorhynchus species occurring in
      avian hosts from both the Western and Eastern Hemispheres. Descriptions of
      juvenile forms of O. nickoli from the intestine of B. jamaicensis are provided
      from recently ingested cystacanths with everted proboscides.

PMID- 17436951
TI  - New species of Rhabdias (Nematoda: Rhabdiasidae) and other helminths from Norops
      capito (Sauria: Polychrotidae) from Nicaragua.
AB  - Rhabdias nicaraguensis n. sp. (Rhabditida: Rhabditidae) from the lungs of Norops
      capito (Sauria: Polychrotidae) is described and illustrated. Rhabdias
      nicaraguensis n. sp. represents the 54th species assigned to the genus and the
      12th from the Neotropical realm. Of the 12 Neotropical Rhabdias species,
      nicaraguensis is most similar to tobagoensis and vellardi. These 3 species have
      equatorial placement of the vulva, inflated cuticle, and 6 small circumoral lips.
      Rhabdias nicaraguensis is easily separated from R. tobagoensis by the shape of
      the buccal cavity and from R. vellardi by body size and shape of the tail.
      Rhabdias nicaraguensis differs from both species by host preference, the amount
      of inflated cuticle covering the body, and the phasmids situated posterior to the
      midpoint of the tail.

PMID- 17436952
TI  - A new gymnophallid trematode from the intestine of mice infected with
      metacercariae from the razor clam Sinonovacula constricta.
AB  - Meiogymnophallus sinonovaculae n. sp. (Digenea: Gymnophallidae) is described from
      metacercariae found in the razor clam, Sinonovacula constricta, in the Republic
      of Korea, and adults recovered from the small intestine of experimentally
      infected mice. The worms are characterized by paired clusters of vitelline
      follicles, a well-developed pars prostatica with abundant prostate cells, a
      voluminous undivided seminal vesicle (in adults and metacercariae), and large,
      grouped, domelike sensory papillae on the ventral surface anterior to the ventral
      sucker (in metacercariae). This new species resembles the type species
      Meiogymnophallus affinis, but differs in having compact, elliptical, and 4-5
      lobed vitellaria, and an excretory vesicle with bicornuated anterior arms
      reaching to the oral sucker. This is the second documentation of the presence of
      a species of Meiogymnophallus in the Republic of Korea.

PMID- 17436953
TI  - First larval record of Mesocestoides in carnivora of Tenerife (Canary Islands).
AB  - Larvae of Mesocestoides sp. were recovered in Tenerife (Canary Islands) in 2004
      from the peritoneal cavities of 2 domestic dogs and a domestic cat. Morphological
      and molecular identification were carried out. Mesocestoides litteratus from
      Vulpes vulpes was sequenced for the first time using the ITS-2 region (18S rDNA),
      and was included in the phylogenetic analysis to compare the sequence variability
      among these and other Mesocestoides spp. belonging to different carnivores.
      Phylogenetic studies were carried out based on maximum parsimony and neighbor
      joining analysis. The results showed the relationships between these and other
      previously published Mesocestoides species. Moreover, it is demonstrated that
      Mesocestoides sp. from Tenerife comprises a previously unreported sequence. This
      is the first larval record of Mesocestoides sp. in domestic animals from
      Tenerife, Canary Islands, Spain.

PMID- 17436954
TI  - Further study of Contracaecum pelagicum (Nematoda: Anisakidae) in Spheniscus
      magellanicus (Aves: Spheniscidae) from Argentinean coasts.
AB  - The anisakid species Contracaecum pelagicum Johnston and Mawson, 1942, is
      reported for first time at 2 different sites on the Argentine coast (Peninsula
      Valdes, 42 degrees 04'S, 63 degrees 38'W and Mar del Plata, 38 degrees 05'S, 57
      degrees 38'W), parasitizing the Magellanic penguin, Spheniscus magellanicus
      Foster. Morphometric analysis and further studies of adult specimens of C.
      pelagicum were done using light and scanning electron microscopy. The presence of
      bifurcated interlabia differentiates the present species from most others in the
      genus, except (1) from Contracaecum travassosi, which possesses higher interlabia
      and longer spicules, and a blunt, more constrained tail; (2) from Contracaecum
      rudolphii, which has longer spicules, blunter spicule tips, postparacloacal
      papillae with oblique disposition, and a blunter constrained tail; (3) from
      Contracaecum eudyptulae, which has a blunter tail and longer spicules; and (4)
      from Contracaecum variegatum, which possesses smaller-diameter, hooklike
      extensions on auricle lips, and a less robust interlabium with a more marked
      furrow. In this paper we present the first detailed description of C. pelagicum
      adults from S. magellanicus. Morphometric data between adult specimens of C.
      pelagicum from S. magellanicus and those from the black-browed albatross,
      Diomedea melanophris Temminck, from Argentinean coasts were compared. In
      addition, fourth-stage larvae that parasitized both hosts were assigned to a
      nondeterminated Contracaecum species. Ecological parameters for adults and larvae
      nematodes were calculated.

PMID- 17436955
TI  - A new dicrocoeliid from the bank vole Clethrionomys glareolus (Rodentia:
      Microtidae) from Poland.
AB  - A new dicrocoeliid trematode, Brachylecithum glareoli n. sp., is described from
      the biliary ducts of the bank vole, Clethrionomys glareolus, in southwest Poland.
      This is the first dicrocoeliid species described in rodents from Poland. It is
      characterized mainly by the maximum body width at the level of the vitellaria;
      large, longitudinally oval testes; round, or transversely oval, ovary that is
      smaller than the testes; vitellaria located in the midbody; cirrus sac dorsally
      overlapping ventral sucker, but never reaching beyond half of its length; and
      large, distinctly elongated eggs.

PMID- 17436956
TI  - A new mermithid nematode from Ablabesmyia monilis (L.) (Diptera: Chironomidae) in
      northern Minnesota.
AB  - Limnomermis steineri n. sp. (Nematoda: Mermithidae) is described from the
      hemocoel of male, female, and intersex imagos of Ablabesmyia (s. str.) monilis
      (L.) eclosing from Lake Ozawindib and Lake Alice Bog in northern Minnesota during
      summers 2000-2005. The species is distinguished from other described members of
      the genus. Paramermis rosea is returned to Limnomermis. A review of adequately
      described members of the genus is included. One species of the genus has been
      reported previously from the Nearctic Realm. Emphasis is placed on the need for
      host identification, larger number of specimens of both mermithid sexes, and
      information on the intensity of infections to enable more precise range
      comparisons in mermithid biometrics.

PMID- 17436957
TI  - Two new species of Rhabdias (Nematoda: Rhabdiasidae) from the marine toad, Bufo
      marinus (L.) (Lissamphibia: Anura: Bufonidae), in Central America.
AB  - Two new Rhabdias species are described from the lungs of the cane toad Bufo
      marinus (L.) from Costa Rica and Nicaragua. Rhabdias alabialis n. sp. differs
      from other known species of the genus by the remarkable morphology of its head
      end, i.e., the absence of lips or pseudolabia, the slitlike oral opening, and the
      triangular shape of the buccal capsule in apical view. Rhabdias
      pseudosphaerocephala n. sp. is identified as a form previously known in Central
      and South America as Rhabdias sphaerocephala Goodey, 1924, a species initially
      described from toads in Europe. The new species is differentiated from R.
      sphaerocephala based on head-end morphology and sequences of nuclear rDNA.

PMID- 17436958
TI  - A new rhabdochonid from the blue striped chub Sectator ocyurus (Osteichthyes:
      Kyphosidae) in Chamela Bay, Mexico.
AB  - Megachona chamelensis n. gen., n. sp. is described from the intestinal cecae of
      blue striped chub Sectator ocyurus (Kyphosidae, Perciformes), from Chamela Bay,
      Mexico. Megachona n. gen. most closely resembles Beaninema Caspeta-Mandujano,
      Moravec, and Salgado-Maldonado, 2001; Fellicola Petter and Koie, 1993; and
      Rhabdochona Railliet, 1916. The main characters that distinguish the new genus
      from all other rhabdochonids include a longer than wide funnel-shaped prostom and
      cuticular longitudinal ridges of prostom forming anteriorly subterminal massive
      toothlike structures followed posteriorly by irregularly arranged smaller teeth.
      This finding brings the total number of genera of Rhabdochonidae of marine fish
      in Mexico to 2. The new species is characterized by having a smaller number of
      cuticular longitudinal ridges in the male prostom than in the female prostom,
      forming massive toothlike structures in its subterminal portion, followed by more
      minute teeth in the female than in the male, a slender tail end with a broad tip,
      the distal part of the left spicule with a lanceolate end, a straight right
      spicule without a dorsal barb, 1 pair of precloacal and 3 pairs of postcloacal
      papillae, and a smooth egg surface.

PMID- 17436959
TI  - Two new species of parasitic nematodes from the dogtooth tuna Gymnosarda unicolor
      (Pisces) off the Maldive Islands.
AB  - Two new nematode species, Philometra gymnosardae n. sp. (Philometridae) and
      Heptochona maldivensis n. sp. (Rhabdochonidae), are described from the dogtooth
      tuna Gymnosarda unicolor (Ruppell) (Scombridae, Perciformes) from the Indian
      Ocean off the Maldive Islands (Republic of Maldives). The former species is
      characterized mainly by unequal, conspicuously long (859 and 435 microm)
      spicules; the structure of the caudal end in the male (found in the host's
      stomach); by markedly large, oval cephalic papillae (n = 8) of the outer circle;
      the presence of a small, anterior bulb on the very long esophagus; and 2 large
      caudal projections in the gravid female (parasitic in the host's body cavity).
      This is the first-known species of Philometra whose gravid females are present in
      the body cavity of tuna fishes. Heptochona maldivensis resembles H. stromatei but
      differs mainly in the position of deirids, shape of the muscular esophagus,
      character of postanal papillae, length of the left spicule (648 microm), much
      larger body measurements, location in the host (stomach), and the host type.
      Rhabdochona parastromatei Bilqees, 1971, is synonymized with H. stromatei,
      whereas Heptochona sindica Akram and Pie de Imprenta, 1988, and H. rivdica Akram,
      1988, are invalid names. Heptochona varmai is transferred to another genus as
      Rhabdochona varmai (Gupta and Masoodi, 1990) n. comb. Rhabdochona varmai,
      Heptochona schmidtii Arya, 1991, and Rhabdochona marina Lakshmi and Sudha, 1999,
      are considered species inquirendae.

PMID- 17436960
TI  - A new species of Pomphorhynchus (Acanthocephala: Palaeacanthocephala) in
      freshwater fishes from central Chile.
AB  - This study describes a new species of Pomphorhynchus collected from Percilia
      gillissi Girard, 1855 from the Zanartu canal, between the sister basins of the
      Itata and Laja rivers, in central Chile. Pomphorhynchus moyanoi n. sp. is
      characterized by an asymmetrical, well-differentiated subspherical bulb and 12-14
      longitudinal rows of 13-14 hooks; the third and the fourth hook in each row are
      stout. Among South American species, P. moyanoi n. sp. shows some similarities to
      the Chilean species P. yamagutii Schmidt & Hugghins, 1973, but it differs in
      having a longer neck, larger bulb, and different proboscis armature arrangement.
      Pomphorhynchus moyanoi n. sp. differs from P. patagonicus Ortubay, Ubeda, Semenas
      & Kennedy 1991, in the bulb shape (protuberances), number of rows, fourth hook
      size and basal hook size. Pomphorhynchus moyanoi n. sp. also differs from P.
      sphaericus in the arrangement of hooks (number of rows and hooks per row), length
      and width of the proboscis, neck width, and symmetry of the bulb.

PMID- 17436961
TI  - Two new species of Austrobdella (Hirudinida: Piscicolidae) from Chile.
AB  - Austrobdella coliumicus n. sp. is described from Coliumo Bay, Chile. It is
      characterized by a continuous, external coelomic canal (= marginal lacuna), 5
      pairs of testisacs, accessory gland cells, a body not distinctly divided into
      trachelosome and urosome, 2 pairs of dorsal ocelli on the trachelosome, dorsal
      and ventral segmental ocelli present on the urosome, green overall pigmentation
      with transverse brown bands, and the absence of conducting tissue. Austrobdella
      coliumicus is distinguished from other species of Austrobdella by the presence of
      2 pairs of ocelli on the trachelosome and a more cylindrical body. It is unusual
      that this leech was collected from inside the mantle cavity of the razor clam,
      Ensis macha. Austrobdella losmoliniensis n. sp. is described from the electric
      ray, Discopyge tschudii, collected at Los Molinos, Chile. It is characterized by
      a continuous, external coelomic canal; 5 pairs of testisacs; accessory gland
      cells; a body distinctly divided into trachelosome and urosome; 1 pair of eyes on
      the oral sucker; overall black pigmentation with unpigmented areas; and the
      absence of conducting tissue. Austrobdella losmoliniensis can be distinguished
      from other species of Austrobdella by the combination of 1 pair of eyes on the
      oral sucker and black pigmentation.

PMID- 17436962
TI  - Balb/Cj male mice do not feminize after infection with larval Taenia crassiceps.
AB  - Balb/cJ mice fail to mount an immune response capable of clearing infection with
      larval Taenia crassiceps. Additionally, male Balb/cJ mice display a lag in larval
      growth of approximately 3 wk as compared to growth in female mice. It has been
      reported that male Balb/ cAnN mice generate a protective immune response early in
      infection, and become permissive to larval growth after they feminize (200-fold
      increase in serum estradiol and 90% decrease in serum testosterone). To determine
      if a different strain of Balb/c mice (Balb/cJ) also feminize, serum was collected
      from infected male mice for 16 wk and levels of 17-beta-estradiol and
      testosterone were measured via ELISA. In addition, the mounting responses of 12-
      and 16-wk infected male mice, as well as uninfected control mice, were determined
      after isolation with a female mouse. The results of these experiments show that
      male Balb/cJ mice do not feminize during infection with larval T. crassiceps.
      There was no significant change in serum levels of either 17-beta-estradiol or
      testosterone during the course of infection (> 16 wk). Moreover, there was no
      significant decrease in the number of times infected male mice mounted the female
      mouse as compared to uninfected controls. These results suggest that there may be
      variances between the substrains of Balb/c mice that lead to the phenotypic
      differences reported for male Balb/cJ and Balb/cAnN mice.

PMID- 17436963
TI  - The phylogenetic position of Allocreadiidae (Trematoda: Digenea) from partial
      sequences of the 18S and 28S ribosomal RNA genes.
AB  - Species of Allocreadiidae are an important component of the parasite fauna of
      freshwater vertebrates, particularly fishes, and yet their systematic
      relationships with other trematodes have not been clarified. Partial sequences of
      the 18S and 28S ribosomal RNA genes from 3 representative species of
      Allocreadiidae, i.e., Crepidostomum cooperi, Bunodera mediovitellata, and
      Polylekithum ictaluri, and from 79 other taxa representing 78 families of
      trematodes obtained from GenBank, were used in a phylogenetic analysis to address
      the relationships of Allocreadiidae with other plagiorchiiforms/plagiorchiidans.
      Maximum parsimony and Bayesian analyses of combined 18S and 28S rRNA gene
      sequence data place 2 of the allocreadiids, Crepidostomum cooperi and Bunodera
      mediovitellata, in a clade with species of Callodistomidae and Gorgoderidae,
      which, in turn is sister to a clade containing Polylekithum ictaluri and
      representatives of Encyclometridae, Dicrocoelidae, and Orchipedidae, a grouping
      supported by high bootstrap values. These results suggest that Polylekithum
      ictaluri is not an allocreadiid, a conclusion that is supported by reported
      differences between its cercaria and that of other allocreadiids. Although
      details of the life cycle of callodistomids, the sister taxon to Allocreadiidae,
      remain unknown, the relationship of Allocreadiidae and Gorgoderidae is consistent
      with their larval development in bivalve, rather than gastropod, molluscs, and
      with their host relationships (predominantly freshwater vertebrates). The results
      also indicate that, whereas Allocreadiidae is not a basal taxon, it is not
      included within the suborder Plagiorchiata. No support was found for a direct
      relationship between allocreadiids and opecoelids either.

PMID- 17436964
TI  - Flotillin-1 localization on sporozoites oF Eimeria tenella.
AB  - In an attempt to identify parasite surface components involved in the interaction
      with the host cell, the present research focuses on the rafts of Eimeria tenella
      that might be involved in the host cell invasion process. To that end, this study
      was undertaken to investigate the expression of flotillin-1, which is an
      important component and marker of lipid rafts at the plasma membrane of
      sporozoites of E. tenella. The expression of this plasma membrane protein was
      identified by an antibody that specifically reacts with flotillin- and was
      studied by electron microscopy. Flotillin-1 was found to occur in patches on the
      surface of E. tenella sporozoites. Immunoblot analysis of the total proteins of
      the sporozoites showed only 1 band of approximately 48 kDa. This indicates that
      the antibody exclusively recognized the molecules of flotillin-1 expressed on the
      surface of E. tenella sporozoites. The presence of flotillin-1 on the cellular
      membrane of sporozoites predominantly at the apical tip suggests that flotillin-1
      belongs to the invasion machinery of E. tenella.

PMID- 17436965
TI  - Cryptosporidium and Giardia in marine-foraging river otters (Lontra canadensis)
      from the Puget Sound Georgia Basin ecosystem.
AB  - Species of Cryptosporidium and Giardia can infect humans and wildlife and have
      the potential to be transmitted between these 2 groups; yet, very little is known
      about these protozoans in marine wildlife. Feces of river otters (Lontra
      canadensis), a common marine wildlife species in the Puget Sound Georgia Basin,
      were examined for species of Cryptosporidium and Giardia to determine their role
      in the epidemiology of these pathogens. Using ZnSO4 flotation and immunomagnetic
      separation, followed by direct immunofluorescent antibody detection (IMS/DFA), we
      identified Cryptosporidium sp. oocysts in 9 fecal samples from 6 locations and
      Giardia sp. cysts in 11 fecal samples from 7 locations. The putative risk factors
      of proximate human population and degree of anthropogenic shoreline modification
      were not associated with the detection of Cryptosporidium or Giardia spp. in
      river otter feces. Amplification of DNA from the IMS/DFA slide scrapings was
      successful for 1 sample containing > 500 Cryptosporidium sp. oocysts. Sequences
      from the Cryptosporidium 18S rRNA and the COWP loci were most similar to the
      ferret Cryptosporidium sp. genotype. River otters could serve as reservoirs for
      Cryptosporidium and Giardia species in marine ecosystems. More work is needed to
      better understand the zoonotic potential of the genotypes they carry as well as
      their implications for river otter health.

PMID- 17436966
TI  - Evidence of experimental postcyclic transmission of Bothriocephalus acheilognathi
      in bonytail chub (Gila elegans).
AB  - We examined the role that predation of infected conspecific fish and postcyclic
      transmission might play in the life cycle of the Asian fish tapeworm,
      Bothriocephalus acheilognathi (Cestoda: Pseudophyllidea) Yamaguti, 1934. Young-of
      the-year (YOY) bonytail chub (Gila elegans) were exposed to copepods infected
      with B. acheilognathi and subsequently fed to subadult bonytail chub. Within 1 wk
      after consumption of the YOY chub, subadults were necropsied and found infected
      with gravid and nongravid tapeworms. This study provides evidence that postcyclic
      transfer of B. acheilognathi can occur. Postcyclic transmission may be an
      important life history trait of B. acheilognathi that merits consideration when
      studying the impact and distribution of this invasive and potentially pathogenic
      tapeworm.

PMID- 17436967
TI  - Helminth community of scaled quail (Callipepla squamata) from western Texas.
AB  - Forty-eight scaled quail (Callipepla squamata) were collected during August 2002
      at Elephant Mountain Wildlife Management Area in Brewster County, Texas, and
      examined for helminths. Eight species of helminths were found (5 nematodes and 3
      cestodes), representing 2,811 individuals. Of these species, Gongylonema sp.,
      Procyrnea pileata, and Choanotaenia infundibulum are reported from scaled quail
      for the first time. Prevalence of Aulonocephalus pennula, Gongylonema sp.,
      Oxyspirura petrowi, Physaloptera sp., P. pileata, C. infundibulum, Fuhrmannetta
      sp., and Rhabdometra odiosa was 98, 2, 56, 4, 60, 2, 25, and 35%, respectively.
      Aulonocephalus pennula numerically dominated, accounting for 88% of total worms.
      Statistical analyses were performed on the 5 species with > or = 25% prevalence
      using the after-hatch-year host sample (n = 38). Prevalence of P. pileata was
      higher (P = 0.049) in females than in males and higher (P = 0.037) in the sample
      collected from the site that had spreader dams (berms 1-2 m high and 4-55 m long
      constructed in varying sizes to catch and retain rainfall) than the control site
      (no spreader dams). Higher rank mean abundance of A. pennula and O. petrowi (P =
      0.0001 and P = 0.0052, respectively) was found in the host sample collected from
      the site that had spreader dams than the control site. A host gender-by
      collection site interaction (P = 0.0215) was observed for P. pileata. Findings
      indicate that scaled quail are acquiring indirect life cycle helminths in arid
      western Texas habitats.

PMID- 17436968
TI  - Modification of host erythrocyte membranes by trypsin and chymotrypsin treatments
      and effects on the in vitro growth of bovine and equine Babesia parasites.
AB  - In the present study, we investigated the effects of protease pretreatments of
      host erythrocytes (RBC) on the in vitro growth of bovine Babesia parasites
      (Babesia bovis and B. bigemina) and equine Babesia parasites (B. equi and B.
      caballi). The selected proteases, trypsin and chymotrypsin, clearly modified
      several membrane proteins of both bovine and equine RBC, as demonstrated by SDS
      PAGE analysis; however, the protease treatments also modified the sialic acid
      content exclusively in bovine RBC, as demonstrated by lectin blot analysis. An in
      vitro growth assay using the protease-treated RBC showed that the trypsin-treated
      bovine RBC, but not the chymotrypsin-treated ones, significantly reduced the
      growth of B. bovis and B. bigemina as compared to the control. In contrast, the
      growth of B. equi and B. caballi was not affected by any of these proteases.
      Thus, the bovine, but not the equine, Babesia parasites require the trypsin
      sensitive membrane (sialoglyco) proteins to infect the RBC.

PMID- 17436969
TI  - Gastrointestinal helminth fauna of Enyalius perditus (Reptilia: Leiosauridae):
      relation to host age and sex.
AB  - The purpose of this study was to determine how the gastrointestinal
      helminthofauna varies according to the age and sex of the lizard, Enyalius
      perditus, captured in Ibitipoca State Park in the state of Minas Gerais, Brazil,
      and to discuss the ecological and behavioral significance of these relationships.
      Fifty-five specimens of E. perditus were captured in drop traps, then killed,
      necropsied, and examined for the presence of helminths in the gastrointestinal
      tract. Nematodes, including Strongyluris oscari, Oswaldocruzia subauricularis,
      and Aplectana vellardi, were found. This was the first record of the last-named
      species in reptiles, and the first record of the first 2 species in E. perditus.
      The number of helminths increased with snout-vent length and, therefore, age of
      the lizards. Male E. perditus lizards were more heavily infected by nematodes
      than females; the largest numbers of nematodes occurred in the caecum and large
      intestine.

PMID- 17436970
TI  - Mitotic responses to injected extracts of larval and adult Schistosoma mansoni in
      Biomphalaria glabrata: effects of dose and colchicine treatment.
AB  - Biomphalaria glabrata snails injected with extracts of Schistosoma mansoni
      miracidia, mother sporocyst excretory-secretory product, cercariae, and adults,
      showed increased mitotic activity in histological sections of the amebocyte
      producing organ (APO) relative to water-injected controls. The mitotic response
      was generally higher to extracts adjusted to 1.0 mg protein/ml than to a 10-fold
      lower concentration, although in most cases this increase was not statistically
      significant. Colchicine treatment prior to fixation significantly increased the
      number of mitotic figures in APOs of all groups of extract-injected snails, both
      with respect to water-injected controls and, with 1 exception, relative to
      matched colchicine-untreated snails. Extracts of adult worms elicited a
      pronounced mitotic response, suggesting that adults may share a mitogenic
      molecule with larvae. The high variability in counts of mitotic figures may limit
      the usefulness of this histological method.

PMID- 17436971
TI  - Functional richness, functional evenness, and use of niche space in parasite
      communities.
AB  - Most efforts aimed at elucidating the factors responsible for the variation in
      species richness among different parasite communities have focused on host
      characteristics such as body mass or diet. Independently of host features,
      however, the way in which parasites use resources within the host may also affect
      the species richness of the community. The distribution of parasite individuals
      or biomass in niche space determines whether host resources are used evenly, or
      whether there are gaps in resource use, with some parts of the total niche being
      underutilized. Here, the concepts of functional richness and functional evenness
      are applied to parasite communities for the first time, using simple indices.
      Measurements of the distribution of species in niche space within communities,
      such as mapping the distribution of helminths along the length of the host's
      intestine, is standard practice in parasitology. In such cases, functional
      richness is simply the proportion of the total number of intestine sections
      available that are used by at least 1 worm, whereas functional evenness measures
      the evenness in the distribution of worm numbers or biomass across all niche
      sections that are occupied. Data on cestode communities of elasmobranchs are used
      to illustrate the use of these indices, and to show how important they can be in
      tests of ecological hypotheses. The indices presented here capture essential
      features of resource use in parasite communities, and can be useful tools for
      comparative analyses.

PMID- 17436972
TI  - A comparison of dental caries levels in two communities with different oral
      health prevention strategies stratified in different social classes.
AB  - OBJECTIVES: To compare dental caries levels of schoolchildren stratified in
      different social classes whose domestic water supply had been fluoridated since
      birth (Dublin) with those living in an area where fluoridated salt was available
      (Freiburg). METHODS: A representative, random sample of twelve-year-old children
      was examined and dental caries was recorded using World Health Organization
      criteria. RESULTS: A total of 699 twelve-year-old children were examined, 377
      were children in Dublin and 322 in Freiburg. In Dublin the mean decayed, missing,
      and filled permanent teeth (DMFT) was 0.80 and in Freiburg it was 0.69. An
      examination of the distribution of the DMFT score revealed that its distribution
      is highly positively skewed. For this reason this study provides summary analyses
      based on medians and inter-quartile range and nonparametric rank sum tests. In
      both cities caries levels of children in social class 1 (highest) were
      considerably lower when compared with the other social classes regardless of the
      fluoride intervention model used. The caries levels showed a reduced disparity
      between children in social class 2 (medium) and 3 (lowest) in Dublin compared
      with those in social class 2 and 3 in Freiburg. CONCLUSIONS: The evidence from
      this study confirmed that water fluoridation has reduced the gap in dental caries
      experience between medium and lower social classes in Dublin compared with the
      greater difference in caries experience between the equivalent social classes in
      Freiburg. The results from this study established the important role of salt
      fluoridation where water fluoridation is not feasible.

PMID- 17436973
TI  - Prevalence and severity of dental caries in adolescents aged 12 and 15 living in
      communities with various fluoride concentrations.
AB  - OBJECTIVES: To determine the experience, prevalence, and severity of dental
      caries in adolescents naturally exposed to various fluoride concentrations.
      METHODS: A cross-sectional census was conducted on 1,538 adolescents aged 12 and
      15 years living at high altitude above sea level (> 2,000 m or > 6,560 ft) in
      above-optimal fluoridated communities (levels ranging from 1.38 to 3.07 ppm) of
      Hidalgo, Mexico. Sociodemographic and socioeconomic data were collected using
      questionnaires. Two previously trained and standardized examiners performed the
      dental exams. RESULTS: Caries prevalence was 48.6 percent and mean of decay,
      missing, and filling teeth (DMFT) for the whole population was 1.15 +/- 1.17. In
      terms of severity, 9.6 percent of the adolescents had DMFT > or = 4, and 1.7
      percent had > or = 7. The significant caries index (SiC) was 2.41 in the group of
      12-year-olds, and 3.46 in the 15-year-olds. Higher experience and prevalence were
      observed in girls, in children with dental visit in the past year, those in the
      wealthiest socioeconomic status (SES) (quartiles 2, 3, and 4), those whose locale
      of residence is in San Marcos and Tula Centro, and in fluorosis-free children and
      those with moderate/severe fluorosis. In an analysis of caries severity (DMFT >
      or = 4), both adolescents with very mild/mild and moderate/severe dental
      fluorosis have higher caries severity. CONCLUSIONS: The results indicated that
      caries experience, prevalence, and severity as well as SiC index among 12- and 15
      year-old adolescents were relatively low. Sociodemographic and socioeconomic
      variables commonly associated with dental caries were also observed in Mexican
      adolescents. Unlike other studies, we found that caries increased with higher
      SES. Fluoride exposure (measured through fluorosis presence) does not appear to
      be reducing the caries prevalence (DMFT > 0) or caries severity (DMFT > or = 4)
      in these high-altitude communities.

PMID- 17436974
TI  - Predictors of dental caries development in 1.5-year-old high-risk children in the
      Japanese public health service.
AB  - OBJECTIVES: The purpose of this study was to construct prediction models for 1.5
      year-old children who were at risk for the development of caries. METHODS: The
      participants were 5,107 Japanese children who resided in 21 municipalities in the
      Shizuoka prefecture and received oral health examinations at both 1.5 and 3 years
      old. General practitioners in the respective municipalities conducted the
      examination and the evaluation of plaque deposit. At the examination at 1.5 years
      old, the guardians were asked to complete a questionnaire concerning the child
      care environment and the health habits of the children and themselves. They were
      divided into four groups based on the population of the concerned municipality.
      Approximately 30 percent of the subjects in each group were found to be in the
      high-risk category (deltadft > or = 1 during both examinations). A stepwise
      multivariate logistic regression analysis in each group was performed using high
      risk subjects as the dependent variable and 28 independent variables from the
      examination at 1.5 years old and the questionnaire. RESULTS: A significant model
      could be constructed for each group using eight to 14 independent variables,
      respectively. The variables common to more than three groups are related to the
      child's characteristics, especially sugar consumption, feeding, and caries
      experiences. The predictive ability of the models had a sensitivity of 58.0 to
      64.0 percent and a specificity of 64.1 to 70.5 percent. Because the negative
      predictive value was 77.4 to 80.5 percent, these models might be considered to be
      in the permissible range. CONCLUSIONS: The models could not predict caries risk
      but may be able to predict those cases who will not develop caries.

PMID- 17436975
TI  - Racial and ethnic variation in the provision of dental procedures.
AB  - OBJECTIVES: Most of the available information on racial/ethnic disparities in
      oral health is based on differences in sociodemographic variables related to
      dental disease burden, dental visits, and access to care. However, very little is
      known regarding racial/ethnic variation in the provision of dental procedures.
      This study examined trends in the provision of dental procedures and sought to
      determine whether there are racial/ethnic differences in the provision of dental
      procedures. METHODS: This is a retrospective observational study of patients
      treated at a dental training institution. Data for all patients 18 to 60 years of
      age in axiUm (electronic database) for 2001 to 2003 were analyzed. Data include
      demographic information, poverty status, insurance coverage, dental procedure,
      and race/ethnicity. Separate logistic regression models (by dental procedure
      category and year) were fitted while considering race/ethnicity, insurance
      coverage, poverty status, marital status, and age as possible covariates.
      RESULTS: The total number of dental procedures completed by providers increased
      by 14,000 between 2001 and 2003. African-Americans were significantly less likely
      to have restorative procedures [odds ratio (OR): 0.60, 95 percent confidence
      interval (CI): 0.42 to 0.86], (OR: 0.52, 95 percent CI: 0.38 to 0.73), (OR: 0.46,
      95 percent CI: 0.36 to 0.58) in 2001, 2002, and 2003, respectively, than the
      White population. Significant differences in the use of other dental procedures
      (prosthodontics--removable) and oral surgery procedures by race/ethnicity were
      observed. CONCLUSIONS: Substantial racial/ethnic variation in the provision of
      dental procedures exists. This study presents findings beyond anecdotal
      information on racial/ethnic variation in the provision of dental procedures and
      requires further research to compile more detailed data.

PMID- 17436976
TI  - Coping with toothache pain: a qualitative study of low-income persons and
      minorities.
AB  - OBJECTIVES: This study examined the behavioral impact of toothache pain as well
      as self-care strategies for pain relief among minority and low-income
      individuals. METHODS: Eight focus group sessions were conducted with 66
      participants drawn from low-income non-Hispanic White, non-Hispanic Black, and
      Hispanic adults over the age of 20 who had experienced a toothache during the
      previous 12-month period and who had utilized self-care or care from a
      nondentist. RESULTS: Toothache pain was described as intense, throbbing,
      miserable, or unbearable. Focus group participants indicated that toothache pain
      affected their ability to perform normal activities, such as their job,
      housework, social activities, sleeping, talking, and eating, as well as making
      them depressed and affecting their social interactions. Numerous prescription and
      nonprescription medications as well as home remedies and self-care strategies
      were used for pain relief, although these were generally of limited and uncertain
      benefit. While receiving care at a dental office was the most preferable option
      for care, most participants reported multiple barriers, including the cost of
      dental care that resulted in long delays in seeking dental care. The main reason
      for eventually seeking dental care was the severity of the pain. CONCLUSIONS:
      Although removing financial barriers alone may not lead to preventive dental
      visits, it would facilitate more timely visits to dentists to treat toothache
      pain.

PMID- 17436977
TI  - Prevalence of dental anxiety among 5- to 8-year-old Taiwanese children.
AB  - OBJECTIVES: Many people experience discomfort to a greater or lesser degree about
      the prospect of dental treatment. Dental treatment can be a terrible experience,
      especially for children with dental anxiety. This study estimated the prevalence
      of dental anxiety among 5- to 8-year-old children in Kaohsiung City, Taiwan.
      METHODS: The Children's Fear Survey Schedule-Dental Subscale (CFSS-DS) was
      translated into Chinese, and a receiver operating characteristic (ROC) curve was
      made based on criteria determined from pretest clinical observations of a sample
      population to set a cutoff score. Then, the parental CFSS-DS was used as a
      screening tool to survey the dental anxiety levels of 5- to 8-year-old children
      at kindergartens and elementary schools in Kaohsiung City, Taiwan. Participants
      were selected by stratified random sampling. The stratification was done by
      geographic district, age group, and sex. A total of 3,597 valid questionnaires
      were collected. RESULTS: The Chinese version of the CFSS-DS had an optimal cutoff
      score of 38/39 (sensitivity was 0.857, specificity was 0.882) with an area under
      the ROC curve of 0.912. The estimated prevalence of dental anxiety among 5- to 8
      year-old children in Kaohsiung City was 20.6 percent. The dental anxiety score
      was found to decrease as age increased; primary school boys had significantly
      lower scores. CONCLUSIONS: The prevalence of dental anxiety was found to be high
      for 5- to 8-year-old Taiwanese children. The study's findings point to the urgent
      need for preventive health education and intervention programs in Taiwan to
      promote children's oral health and reduce dental anxiety.

PMID- 17436978
TI  - Oral health in Veterans Affairs patients diagnosed with serious mental illness.
AB  - OBJECTIVES: We evaluated patient and medication treatment factors associated with
      self-reported oral health status in patients diagnosed with serious mental
      illness (SMI) in a large, national sample of patients in the Veterans Affairs
      (VA) health system. METHODS: 4,769 patients (mean age = 55, 7.8 percent women)
      were included from the VA's 1999 National Psychosis Registry (NPR) for whom the
      oral health information gathered by the VA's Large Health Survey of Veterans was
      available. Current (1999) psychotropic medication data were ascertained from the
      NPR. Multivariable logistic regression analyses were used to determine the
      patient factors (e.g., sociodemographic, enabling, and treatment factors)
      associated with poor or fair overall dental health, and with having tooth or
      mouth problems that made it difficult to eat. RESULTS: While 61.0 percent of
      persons with SMI self-reported fair to poor dental health, 34.1 percent reported
      that oral health problems made it difficult for them to eat. Patients who were
      not employed, experiencing financial strain, who smoked, who were prescribed
      tricyclic antidepressants, or prescribed selective serotonin reuptake inhibitors
      were more likely to report poor or fair dental health. These variables were also
      associated with having tooth or mouth problems. CONCLUSIONS: Suboptimal oral
      health was self-reported with substantial prevalence among patients with SMI, a
      problematic finding given its consequences for general health, social
      functioning, and quality of life. Greater efforts are needed to improve oral
      health outcomes among patients with SMI by facilitating access to dental care and
      addressing mutable factors such as smoking and medication side effects.

PMID- 17436979
TI  - Periodontal health status in a cohort of young US Navy personnel.
AB  - OBJECTIVES: Neither the prevalence of periodontal disease nor long-term trends in
      periodontal health among US military personnel has been well studied. The authors
      analyzed dental records to assess the prevalence and severity of periodontal
      disease, characterize changes in periodontal health, and determine the
      associations of age, race, gender, and tobacco use with periodontal status among
      US Navy personnel. METHODS: Dental records from 1,107 personnel who entered
      military service in 1997 were gathered from eight US Navy dental treatment
      facilities. Demographic information, tobacco use status, and periodontal health
      status, as reflected by the Periodontal Screening and Recording (PSR) information
      recorded at each required dental examination during the 4-year observational
      period (1997 to 2001), were collected. To improve sensitivity in measuring the
      extent of periodontal disease, the standard five-point PSR scale was reexpressed
      as a "PSR grade." RESULTS: Over 98 percent of Navy recruits exhibited some level
      of periodontal disease at initial examination. Most (76 percent) exhibited
      gingivitis of varying severity. Over a mean observational period of 3.4 years, 91
      percent of subjects received at least one oral prophylaxis, and over 60 percent
      received two to four prophylaxes. Subjects with severe periodontal conditions
      received as many as 22 appointments for prophylaxis or periodontal therapy. From
      initial to final examination, periodontal status improved for 29.2 percent of
      subjects, deteriorated for 31.3 percent, and remained unchanged for 39.5 percent.
      Subjects presenting initially with healthy periodontia, or gingivitis without
      evidence of periodontitis, tended to deteriorate or remain unchanged, while those
      exhibiting periodontitis tended to improve with periodontal therapy. Race (non
      White) and greater age at entry were significantly associated with increased risk
      for poorer periodontal health at both initial and final examination. CONCLUSIONS:
      Although a needs-based dental care model appears effective in managing
      periodontal disease among those receiving active therapy, patients who receive
      sporadic care may deteriorate over time. To maintain periodontal health in this
      population, appropriate preventive and periodontal therapies should be provided
      soon after entry and repeated at intervals specific to individual patient need.

PMID- 17436980
TI  - Use of dental care by elderly Chinese immigrants in Canada.
AB  - OBJECTIVES: This study examines the predictors for elderly Chinese immigrants'
      use of dental care services. METHODS: In 2003, a study entitled "Health and Well
      Being of Older Chinese in Canada" collected data from seven cities in which 2,272
      Chinese Canadians aged 55 years and older were surveyed. Data from 1,537 of these
      individuals were used to examine the use of dental care services by the elderly
      Chinese. Hierarchical logistic regression analysis was used to examine the
      predicting factors for use of dental care. RESULTS: More than half (52.1 percent)
      of the elder Chinese immigrants did not use any dental care services within the
      past year of the study. Being older, living in Quebec, and having poorer physical
      health reduced the probability that an older Chinese immigrant would use dental
      care services. On the other hand, being an immigrant from Hong Kong, having lived
      in Canada for a longer period of time, strong social support, and having dental
      problems increase the probability of dental service use. DISCUSSION: The findings
      support the need for considering the cultural characteristics and background of
      elderly Chinese immigrants when strengthening oral health promotion. This should
      encompass understanding of the holistic concept of health that includes oral
      health and its connections with other physical health issues.

PMID- 17436981
TI  - Compliance with fluoride supplements provided by a dental hygienist in homes of
      low-income parents of preschool children in Quebec.
AB  - OBJECTIVE: This study aimed to assess the compliance with fluoride supplements
      provided at home by a dental hygienist to mothers of at-risk preschool children.
      METHODS: Participants were recruited during pregnancy of low-income women. On the
      first visit, the mothers of 60 infants aged 6 to 9 months were handed free
      fluoride supplements. A questionnaire was administered at that time and after 6
      and 12 months to assess compliance during the preceding week. RESULTS: At the
      beginning of the study, none of the mothers reported having given fluoride
      supplements, in comparison with 73 percent of mothers of 44 infants who received
      all three visits at the end of follow-up; 48 percent reported fluoride supplement
      use on a daily basis. CONCLUSIONS: Removal of financial and physical barriers and
      personal professional involvement are good strategies to achieve compliance with
      fluoride supplements. Further assessment regarding the possible application of
      this intervention to other professional or cultural contexts is warranted.

PMID- 17436983
TI  - What is a national health policy?
AB  - Unfortunately, most nation states have taken "health policy" to mean "medical
      care policy." Medical care, however, is only one variable in a nation's health
      equation. The article describes what the main components of a national health
      policy should be, including (1) the political, economic, social, and cultural
      determinants of health, the most important determinants of health in any country;
      (2) the lifestyle determinants, which have been the most visible types of public
      interventions; and (3) the socializing and empowering determinants, which link
      the first and second components of a national health policy: the individual
      interventions and the collective interventions. The author discusses the
      indicators that should be used for each component and for each intervention. The
      feasibility of this approach depends to a large degree on the political will of
      the national authorities and the broad understanding of the actual determinants
      of health. A good first step is the National Health Policy plan developed by the
      Swedish social democratic government. This article builds on and expands on that
      model.

PMID- 17436982
TI  - Dental amalgam and multiple sclerosis: a systematic review and meta-analysis.
AB  - OBJECTIVES: Amalgam restorations have long been controversial due to their
      mercury content. Allegations that the mercury may be linked to nervous disorders
      such as Alzheimer's, chronic fatigue syndrome, and multiple sclerosis (MS) have
      fueled the calls for the removal of amalgam restorations from dentists'
      armamentarium. To explore and quantify the association between amalgam
      restorations and MS we have conducted a systematic review and meta-analysis of
      the literature. METHODS: A systematic search in Medline (from 1966 to April
      2006), EMBASE (2006, Week 16), and the Cochrane library (Issue 2, 2006) for
      English-language articles meeting specific definitions of MS and amalgam exposure
      was conducted. Studies were also identified using the references of retrieved
      articles. Studies were independently reviewed by two authors and disagreements
      were resolved by consensus. Studies were selected based on an a priori of defined
      criteria. Odds ratios (ORs) or relative risks were pooled using the random
      effects model. Heterogeneity was assessed using Q statistics. RESULTS: The pooled
      OR for the risk of MS among amalgam users was consistent, with a slight,
      nonstatistically significant increase between amalgam use and risk of MS.
      CONCLUSION: Future studies that take into consideration the amalgam restoration
      size and surface area along with the duration of exposure are needed in order to
      definitively rule out any link between amalgam and MS.

PMID- 17436984
TI  - Is the United States a good model for reducing social exclusion in Europe?
AB  - Advocates of U.S.-style labor market flexibility have long argued that Europe
      could generate jobs and lower unemployment if the continent's economies followed
      the example of the United States. More recently, proponents of the U.S. model
      have suggested that labor market deregulation also holds out the possibility of
      reducing the problem of "social exclusion" in Europe, primarily because
      unemployment is one of the worst forms of social exclusion and contributes to
      other forms of social marginalization. The authors review a broad range of social
      and economic indicators and conclude that the United States fares poorly compared
      with much of Europe on social measures. Meanwhile, U.S.-style flexibility has had
      only mixed success in improving employment outcomes, and the U.S. economy
      consistently provides lower levels of economic mobility than economies in Europe.

PMID- 17436985
TI  - Neoliberalism as a class ideology; or, the political causes of the growth of
      inequalities.
AB  - Neoliberalism is the dominant ideology permeating the public policies of many
      governments in developed and developing countries and of international agencies
      such as the World Bank, International Monetary Fund, World Trade Organization,
      and many technical agencies of the United Nations, including the World Health
      Organization. This ideology postulates that the reduction of state interventions
      in economic and social activities and the deregulation of labor and financial
      markets, as well as of commerce and investments, have liberated the enormous
      potential of capitalism to create an unprecedented era of social well-being in
      the world's population. This article questions each of the theses that support
      such ideology, presenting empirical information that challenges them. The author
      also describes how the application of these neoliberal policies has been
      responsible for a substantial growth of social inequalities within the countries
      where such policies have been applied, as well as among countries. The major
      beneficiaries of these policies are the dominant classes of both the developed
      and the developing countries, which have established worldwide class alliances
      that are primarily responsible for the promotion of neoliberalism.

PMID- 17436986
TI  - Variation of socioeconomic gradients in children's developmental health across
      advanced Capitalist societies: analysis of 22 OECD nations.
AB  - Within societies, there is a well-established relation between socioeconomic
      position and a wide range of outcomes related to well-being, and this relation is
      known to vary in magnitude across countries. Using a large sample of nations, the
      authors explored whether differences in social policies explain differences in
      socioeconomic gradients across nations. Analyses were conducted on reading
      literacy in 15-year-olds, as an outcome related to cognitive development and to a
      host of factors that contribute to future well-being, including educational
      attainment and health. The results show a systematic variation in socioeconomic
      gradients and average scores across countries. Scores were favorable in countries
      with a long history of welfare state regimes, but countries where institutional
      change unfolded more recently and rapidly, or where welfare states are less well
      developed, clustered at the bottom of the rankings. Strong support was found for
      the "flattening up" hypothesis, which suggests that nations with higher average
      scores have less socioeconomic inequality in scores (or flatter gradients).
      Potential explanations for the observed patterns include differences between
      nations in the extent and distribution of income and social goods important for
      children's development.

PMID- 17436987
TI  - How close have universal health systems come to achieving equity in use of
      curative services? A systematic review.
AB  - Most governments in established market economies have developed universal systems
      of health care, but these are being increasingly threatened by widespread health
      sector reforms. Hence, it is more important than ever to monitor the effects of
      policy changes on the ability of universal systems to achieve their equity goals.
      This article provides evidence for such monitoring. The authors present the
      results of a systematic review of equity in use of curative health services in
      universal systems, together with a critical appraisal of the essential components
      of studies to address this question. Of the 79 studies identified that addressed
      the review question, only 26 met the inclusion criteria and adjusted for
      differential health need across socioeconomic groups. The authors found a pro
      rich bias in use of specialist hospital services and a reasonably equitable
      access to primary health care by different socioeconomic groups. There was a wide
      inter-study variation in the difference in utilization rates between people of
      high and low socioeconomic groups. Improvements are needed in the way that equity
      in universal systems is monitored, with particular attention to how "need" is
      defined and to the impact on patients of indirect costs.

PMID- 17436988
TI  - Quantifying the health benefits of primary care physician supply in the United
      States.
AB  - This analysis addresses the question, Would increasing the number of primary care
      physicians improve health outcomes in the United States? A search of the PubMed
      database for articles containing "primary care physician supply" or "primary care
      supply" in the title, published between 1985 and 2005, identified 17 studies, and
      10 met all inclusion criteria. Results were reanalyzed to assess primary care
      effect size and the predicted effect on health outcomes of a one-unit increase in
      primary care physicians per 10,000 population. Primary care physician supply was
      associated with improved health outcomes, including all-cause, cancer, heart
      disease, stroke, and infant mortality; low birth weight; life expectancy; and
      self-rated health. This relationship held regardless of the year (1980-1995) or
      level of analysis (state, county, metropolitan statistical area (MSA), and non
      MSA levels). Pooled results for all-cause mortality suggest that an increase of
      one primary care physician per 10,000 population was associated with an average
      mortality reduction of 5.3 percent, or 49 per 100,000 per year.

PMID- 17436989
TI  - Methods for recruiting white, black, and hispanic working-class women and men to
      a study of physical and social hazards at work: the United for Health study.
AB  - Despite research on work and health having a long-standing concern about unjust
      exposures and inequitable burdens of disease, there are few studies that document
      the joint distribution and health effects of physical and psychosocial hazards
      (e.g., noise, dusts, fumes, and job strain) and social hazards (e.g., racial
      discrimination and gender harassment) encountered at work. Also, there is a
      paucity of data on how these exposures, singly and combined, are distributed in
      relation to sociodemographic characteristics including race/ethnicity, gender,
      socioeconomic position, and nativity. This article presents a conceptual model
      for redressing these knowledge gaps and describes recruitment strategies and the
      characteristics of study participants in the United for Health study. Working
      with labor unions, the authors recruited 14 (67%) of 21 worksites from
      manufacturing, meat processing, retail, and transportation, and 1,282 workers
      (72% response rate), of whom 62 percent were men, 36 percent were women, 39
      percent were black, 23 percent were Hispanic, 25 percent were white, 31% earned
      less than a living wage, 40 percent were below the poverty level, and 23 percent
      had less than a high school education.

PMID- 17436990
TI  - Remapping worker citizenship in contemporary occupational health and safety
      regimes.
AB  - The article draws on the rapidly growing field of citizenship studies to map and
      explore the dynamics of contemporary occupational health and safety (OHS)
      regulation. Using two key dimensions of OHS regulation (protection and
      participation), the author constructs four ideal types of worker citizenship
      (market, public, private industrial, and public industrial citizens).
      Historically, workers have been written into OHS regulatory regimes in each of
      these ways. Most recently lawmakers have created a new species of OHS regimes,
      best described as mandated partial self-regulation. Its distinguishing
      characteristic is its flexibility, such that worker citizenship can take on any
      of the forms previously described, often without changing the statutory
      framework. Using Ontario as an example, the study finds that in the late 20th
      century, workers made significant strides toward public industrial citizenship
      and, surprisingly, even under a neoconservative government, workers successfully
      defended their participatory rights and saw their right to protection modestly
      strengthened through increased enforcement. The conditions under which this
      regime operates, however, constantly threaten to undermine the efficacy of worker
      participation rights and to weaken the enforcement effort. Some suggestions are
      made about using a citizenship discourse to revitalize the worker OHS movement
      and strengthen OHS rights.

PMID- 17436991
TI  - The dispossession of African wealth at the cost of Africa's health.
AB  - This article synthesizes new data about the outflow of Africa's wealth, to reveal
      structural factors behind the continent's ongoing underdevelopment. The flow of
      wealth out of sub-Saharan Africa to the North occurs primarily through
      exploitative debt and finance, phantom aid, capital flight, unfair trade, and
      distorted investment. Although the resource drain from Africa dates back many
      centuries--beginning with unfair terms of trade, amplified through slavery,
      colonialism, and neocolonialism--today, neoliberal (free market) policies are the
      most direct causes of inequality and poverty. They tend to amplify preexisting
      class, race, gender, and regional disparities and to exacerbate ecological
      degradation. Reversing this outflow is just one challenge in the struggle for
      policy measures to establish a stronger funding base for the health sector.

PMID- 17436992
TI  - Patients without borders: the emergence of medical tourism.
AB  - A growing number of patients from the United States and other developed countries
      are traveling abroad with the express purpose of obtaining health care, including
      elective surgery and long-term care. This trend is not innocuous. It can lead
      developing countries to emphasize technology-intensive tertiary care for
      foreigners at the expense of basic health care for their citizens. Moreover, it
      can exacerbate the brain drain from the public to the private sector. The
      examples of Thailand and India suggest the distorting effects of this trend and
      raise questions of social equity in the distribution of scarce resources.

PMID- 17436993
TI  - Effective appeal strategies and denial management.

PMID- 17436994
TI  - Your UB-04 conversion action plan.

PMID- 17436995
TI  - HTM 01 issues explored in depth.
AB  - IHEEM has staged a succession of seminars titled Decontamination: Focus on HTM
      01, and James Verrinder reports on the final event in the series. The new HTM 01
      on disinfection and sterilisation is the first guidance update for over ten years
      and is due to be published soon.

PMID- 17436996
TI  - Handling radioactive therapeutic waste.
AB  - In its development of cancer treatment services, Belfast City Hospital Trust has
      installed a vacuum drainage system for the control and containment of radioactive
      therapeutic waste.

PMID- 17436997
TI  - Correct ladder use in the workplace.
AB  - Falls from ladders and stepladders cause more than 1,000 major injuries a year
      and around 14 deaths. As a result, the Health and Safety Executive (HSE) has
      produced new guidance to help eliminate accidents in the workplace.

PMID- 17436998
TI  - Capturing qualities of blue sky.
AB  - Artificially created melatonin-supressing blue light can improve patient outcomes
      and invigorate healthcare staff. Nicholas Marshall reports.

PMID- 17436999
TI  - Partnership provides wireless solutions.
AB  - Providing wireless communication solutions at one of the country's largest mental
      health facilities is a partnership between South London & Maudsley NHS Trust
      (SLaM) and Ascom which has been in place for more than 10 years. James Verrinder
      visited the Bethlem Royal Hospital to see the site's communication system at
      work.

PMID- 17437000
TI  - Use of antimicrobial technology set to grow.
AB  - Patients are being given a choice of where they can be treated, and hospital
      cleanliness is likely to influence their decision-making process. Increased use
      of antimicrobial technologies could have major importance in the fight against
      the spread of bacteria and germs. Trevor Payne reports.

PMID- 17437001
TI  - Cardiac centre lights up Blackpool.
AB  - A new cardiac centre at Blackpool's Victoria Hospital is described as an
      excellent example of how the ProCure21 process can work.

PMID- 17437002
TI  - Off-site manufacturing significantly beneficial.
AB  - Off-site manufacture of energy centre systems could help the NHS improve its
      track record of delivering major projects on time and on budget, argues Murdo
      MacDonald, major projects manager for Spirax Sarco.

PMID- 17437003
TI  - Reducing high pressure oxygen system risk.
AB  - A risk management approach to the selection of non-metallic materials used in
      high pressure medical oxygen systems is discussed by Ben Johnson, product manager
      at BeaconMedaes.

PMID- 17437004
TI  - Paths to HaI prevention debated.
AB  - Tackling healthcare-acquired infections needs common sense, a clear pursuit of
      good hygiene practice, sound product purchasing and the maintenance of a
      collective responsibility, a specially convened meeting in Staffordshire
      determined. Nicholas Marshall reports.

PMID- 17437005
TI  - 'Gatekeeper' unit defeats legionella.
AB  - Legionella presents an ongoing cause for concern in any sector where duty of care
      responsibilities prevail. Jo Wolters, microbiologist and sector head of TA-Aqua+
      at Tour & Andersson, describes a recently developed method of legionella
      prevention and control.

PMID- 17437006
TI  - Streamlining electrical distribution.
AB  - Schneider Electric Building Systems and Solutions has proved to be an effective,
      valuable partner in the development of a new PFI-funded acute general hospital
      for the Derby NHS Foundation Trust. The first phase of a pound 350 million
      development is now complete, with Schneider Electric providing an innovative, new
      solution to electrical distribution.

PMID- 17437007
TI  - Is uroflowmetry necessary following hypospadias repair?

PMID- 17437008
TI  - First-line treatment with oxaliplatin and capecitabine in patients with advanced
      or metastatic oesophageal cancer: a phase II study.
AB  - This phase II study assessed the safety and efficacy of oxaliplatin and
      capecitabine in patients with advanced oesophageal cancer. Fifty-one eligible
      patients received oxaliplatin 130 mg m(-2) intravenously on day 1 and
      capecitabine 1000 mg m(-2) orally twice daily on days 1 to 14 in a 21-day
      treatment cycle as first-line treatment for advanced oesophageal cancer. Grade 3
      neutropenia was seen in one patient and anaemia in another patient. No grade 4
      haematological toxicities were observed. Grade 4 non-haematological toxicity
      (lethargy) occurred in one patient (2%). Grade 3 non-haematological toxicity was
      seen in 14 (27%) patients (vomiting and polyneuropathy (8%); nausea (6%);
      lethargy and hand-foot syndrome (4%); and anorexia, diarrhoea, and
      hyperbilirubinaemia (each in one patient)). In 22% of the patients, toxicity was
      the reason for stopping the treatment. The overall response rate was 39%. The
      median overall survival was 8 months; the 1-year survival rate was 26%. In the
      quality of life (QoL) analysis, the emotional well-being improved during
      treatment, but the physical functioning scores declined. The fatigue score on the
      symptom scales increased. Overall, the global QoL score did not change during
      treatment. In conclusion, the activity of oxaliplatin and capecitabine is
      comparable with other chemotherapy regimens in advanced oesophageal cancer with a
      low frequency of grade 3/4 toxicity. Because this treatment can be given on an
      outpatient basis, it is probably less toxic than cisplatin-based therapy and
      preserves QoL during treatment, it is a viable treatment option in patients with
      advanced oesophageal cancer.

PMID- 17437009
TI  - What can we learn from geographical comparisons of childhood cancer survival?
AB  - With improvements in treatment for childhood cancer, comparisons of survival
      rates between countries have become important to inform future health policies
      and treatment strategies. Population-based cancer registry data are viewed as the
      gold standard for such comparisons, but even these have potential confounding
      factors. Here, we review the interpretation of recent geographical comparisons of
      childhood cancer survival from the viewpoint of the British Isles, a region with
      a 45-year record of national population-based cancer registration and a national
      childhood cancer clinical trials organisation in place for nearly 30 years. Using
      national data on referral patterns to tertiary paediatric oncology centres, we
      explore some of the reasons for lower survival rates in the past for some tumour
      groups and anticipate continued improvement in the next decade. Participation in
      international clinical trials coincided with rapid gains in survival for
      hepatoblastoma. This exemplifies the potential benefits of international
      collaborative clinical research, particularly for rare subgroups.

PMID- 17437010
TI  - Expression of eEF1A2 is associated with clear cell histology in ovarian
      carcinomas: overexpression of the gene is not dependent on modifications at the
      EEF1A2 locus.
AB  - The tissue-specific translation elongation factor eEF1A2 is a potential oncogene
      that is overexpressed in human ovarian cancer. eEF1A2 is highly similar (98%) to
      the near-ubiquitously expressed eEF1A1 (formerly known as EF1-alpha) making
      analysis with commercial antibodies difficult. We wanted to establish the
      expression pattern of eEF1A2 in ovarian cancer of defined histological subtypes
      at both the RNA and protein level, and to establish the mechanism for the
      overexpression of eEF1A2 in tumours. We show that while overexpression of eEF1A2
      is seen at both the RNA and protein level in up to 75% of clear cell carcinomas,
      it occurs at a lower frequency in other histological subtypes. The copy number at
      the EEF1A2 locus does not correlate with expression level of the gene, no
      functional mutations were found, and the gene is unmethylated in both normal and
      tumour DNA, showing that overexpression is not dependent on genetic or epigenetic
      modifications at the EEF1A2 locus. We suggest that the cause of overexpression of
      eEF1A2 may be the inappropriate expression of a trans-acting factor. The
      oncogenicity of eEF1A2 may be related either to its role in protein synthesis or
      to potential non-canonical functions.

PMID- 17437011
TI  - Heparan sulphate synthetic and editing enzymes in ovarian cancer.
AB  - Several angiogenic growth factors including fibroblast growth factors 1 and 2
      (FGF1 and FGF2) depend on heparan sulphate (HS) for biological activity. We
      previously showed that all cellular elements in ovarian tumour tissue synthesised
      HS but biologically active HS (i.e. HS capable of binding FGF2 and its receptor)
      was confined to ovarian tumour endothelium. In this study, we have sought to
      explain this observation. Heparan sulphate sulphotransferases 1 and 2 (HS6ST1 and
      HS6ST2) attach sulphate groups to C-6 of glucosamine residues in HS that are
      critical for FGF2 activation. These enzymes were strongly expressed by tumour
      cells, but only HS6ST1 was found in endothelial cells. Immunostaining with the
      3G10 antibody of tissue sections pretreated with heparinases indicated that HS
      proteoglycans were produced by tumour and endothelial cells. These results
      indicated that, in contrast to the endothelium, HS produced by tumour cells may
      be modified by cell-surface heparanase (HPA1) or endosulphatase (SULF). Protein
      and RNA analysis revealed that HPA1 was strongly expressed by ovarian tumour
      cells in eight of ten specimens examined. HSULF-1, which removes specific 6-O
      sulphate groups from HS, was abundant in tumour cells but weakly expressed in the
      endothelium. If this enzyme was responsible for the lack of biologically active
      HS on the tumour cell surface, we would expect exogenous FGF2 binding to be
      preserved; we showed previously that this was indeed the case although FGF2
      binding was reduced compared to the endothelium and stroma. Thus, the combined
      effects of heparanase and HSULF could account for the lack of biologically active
      HS in tumour cells rather than deficiencies in the biosynthetic enzymes.

PMID- 17437012
TI  - The expression of p53-induced protein with death domain (Pidd) and apoptosis in
      oral squamous cell carcinoma.
AB  - The Pidd (p53-induced protein with death domain) gene was shown to be induced by
      the tumour suppressor p53 and to mediate p53-dependent apoptosis in mouse and
      human cells, through interactions with components of both the mitochondrial and
      the death receptor signalling pathways. To study the role of Pidd in clinical
      tumours, we measured its expression by quantitative reverse transcription-PCR in
      microdissected oral squamous cell carcinomas (OSCC) with and without p53
      mutation. Tumour cell apoptosis was assessed by in situ terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labelling. Tumour proliferation was assessed
      by immunohistochemical staining for the Ki-67 antigen. We found a wide range of
      Pidd expression among OSCC. Statistical analysis revealed an association between
      Pidd expression and apoptotic index (Mann-Whitney test, P<0.001), consistent with
      a role of Pidd in apoptosis in this tumour type. Furthermore, we showed a
      positive correlation between apoptotic index and proliferative index that has not
      been previously described for OSCC. There was no correlation between Pidd
      expression and the p53 mutation status of these tumours, suggesting that Pidd
      expression may be regulated by p53-independent mechanisms. Further
      characterisation of these molecular defects in the control of proliferation and
      apoptosis should help in developing treatments that target OSCC according to
      their biological properties.

PMID- 17437013
TI  - Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia
      dysplasia-adenocarcinoma sequence.
AB  - Hypoxia-associated markers are involved in the progression of several
      malignancies, but are relatively unstudied in Barrett's carcinogenesis. Our aim
      was to assess the immunohistochemical expression of hypoxia-inducible factor
      (HIF)-1alpha, HIF-2alpha, erythropoietin (Epo), Epo receptor (Epo-R), Glut-1 and
      vascular endothelial growth factor (VEGF) along with Ki67/MIB-1 in the Barrett's
      metaplasia-dysplasia-adenocarcinoma sequence. Endoscopic biopsies of normal
      squamous epithelium (NSE) (n=20), columnar-lined oesophagus (CLO) (n=15), CLO
      with intestinal metaplasia (n=20), dysplasia (n=17) and Barrett's type
      adenocarcinoma (n=20) were obtained. Immunohistochemistry was performed on the
      paraffin-embedded tissue. A score was calculated for each marker (range 0-300) by
      multiplying intensity (none 0, weak 1, moderate 2, strong 3) by percentage of
      expression (range 0-100). Significant increases in the expression of HIF-2alpha
      (P=0.014), VEGF (P<0.0001), Epo-R (P<0.0001) and Ki67 (P<0.0001) were found as
      tissue progressed from NSE to adenocarcinoma. HIF-2alpha was expressed late in
      the sequence and was only seen in dysplasia and adenocarcinoma. High HIF-2alpha
      expression was seen in 12 out of 20 Barrett's type adenocarcinoma. The late
      expression of HIF-2alpha in the Barrett's carcinogenesis sequence and its high
      expression in adenocarcinoma suggest that it is worth further investigation as a
      marker of disease progression and therapeutic target.

PMID- 17437014
TI  - In breast carcinoma dysadherin expression is correlated with invasiveness but not
      with E-cadherin.
AB  - Reduction/loss of E-cadherin is associated with the development and progression
      of many epithelial tumours. Dysadherin, recently characterised by members of our
      research team, has an anti-cell-cell adhesion function and downregulates E
      cadherin in a post-transcriptional manner. The aim of the present study was to
      study the role of dysadherin in breast cancer progression, in association with
      the E-cadherin expression and the histological type. We have selected ductal
      carcinoma, which is by far the most common type and lobular carcinoma, which has
      a distinctive microscopic appearance. Dysadherin and E-cadherin expression was
      examined immunohistochemically in 70 invasive ductal carcinomas, no special type
      (NST), and 30 invasive lobular carcinomas, with their adjacent in situ
      components. In ductal as well as in lobular carcinoma dysadherin was expressed
      only in the invasive and not in the in situ component, and this expression was
      independent of the E-cadherin expression. Specifically, all 10 (100%) Grade 1, 37
      out of 45(82.2%) Grade 2 and six out of 15 (40%) Grade 3 invasive ductal
      carcinomas showed preserved E-cadherin expression, while 'positive dysadherin
      expression' was found in six out of 10 (60%) Grade 1, 34 out of 45(75.5%) Grade 2
      and all 15 (100%) Grade 3 neoplasms. None of the 30 infiltrating lobular
      carcinomas showed preserved E-cadherin expression, while all the 30 infiltrating
      lobular carcinomas exhibited 'positive dysadherin expression'. Dysadherin may
      play an important role in breast cancer progression by promoting invasion and,
      particularly in lobular carcinomas, it might also be used as a marker of
      invasion.

PMID- 17437016
TI  - The classification of p53 immunohistochemical staining results and patient
      outcome in ovarian cancer.

PMID- 17437017
TI  - Effect of zoledronic acid on the doxycycline-induced decrease in tumour burden in
      a bone metastasis model of human breast cancer.
AB  - Bone is one of the most frequent sites for metastasis in breast cancer patients
      often resulting in significant clinical morbidity and mortality. Bisphosphonates
      are currently the standard of care for breast cancer patients with bone
      metastasis. We have shown previously that doxycycline, a member of the
      tetracycline family of antibiotics, reduces total tumour burden in an
      experimental bone metastasis mouse model of human breast cancer. In this study,
      we combined doxycycline treatment together with zoledronic acid, the most potent
      bisphosphonate. Drug administration started 3 days before the injection of the
      MDA-MB-231 cells. When mice were administered zoledronic acid alone, the total
      tumour burden decreased by 43% compared to placebo treatment. Administration of a
      combination of zoledronic acid and doxycycline resulted in a 74% decrease in
      total tumour burden compared to untreated mice. In doxycycline- and zoledronate
      treated mice bone formation was significantly enhanced as determined by increased
      numbers of osteoblasts, osteoid surface and volume, whereas a decrease in bone
      resorption was also observed. Doxycycline greatly reduced tumour burden and could
      also compensate for the increased bone resorption. The addition of zoledronate to
      the regimen further decreased tumour burden, caused an extensive decrease in bone
      associated soft tissue tumour burden (93%), and sustained the bone volume, which
      could result in a smaller fracture risk. Treatment with zoledronic acid in
      combination with doxycycline may be very beneficial for breast cancer patients at
      risk for osteolytic bone metastasis.

PMID- 17437019
TI  - The clinical and economic benefits of capecitabine and tegafur with uracil in
      metastatic colorectal cancer.

PMID- 17437020
TI  - Prevalence and distribution of HPV genotypes among HIV-infected women in Zambia.
AB  - We screened 145 HIV-infected non-pregnant women at a tertiary care centre in
      Lusaka, Zambia. Liquid-based cytology and human papillomavirus (HPV) genotyping
      with PGMY09/11 biotinylated primers (Roche Linear Array HPV genotyping test)
      maximised sensitivity of cytology and HPV assessments. Among high-risk (HR)
      types, HPV 52 (37.2%), 58 (24.1%) and 53 (20.7%) were more common overall than
      HPV 16 (17.2%) and 18 (13.1%) in women with high-grade squamous intraepithelial
      lesions or squamous cell carcinoma (SCC) on cytology. High-risk HPV types were
      more likely to be present in women with CD4+ cell counts <200 microl(-1) (odds
      ratios (OR): 4.9, 95% confidence intervals (CI): 1.4-16.7, P=0.01) and in women
      with high-grade or severe cervical cytological abnormalities (OR: 8.0, 95% CI:
      1.7-37.4, P=0.008). Human papillomavirus diversity in high-grade lesions and SCC
      on cytology suggests that HPV 16- and 18-based vaccines may not be adequately
      polyvalent to induce protective immunity in this population.

PMID- 17437021
TI  - Phase-I trial of oral fluoropyrimidine anticancer agent (S-1) with concurrent
      radiotherapy in patients with unresectable pancreatic cancer.
AB  - In this phase-I trial, we evaluated the safety of S-1, a novel oral
      fluoropyrimidine anticancer agent, combined with external-beam radiotherapy
      (EBRT) to determine the maximum-tolerated dose and dose-limiting toxicity (DLT)
      in unresectable pancreatic cancer patients. Patients had histologically proven
      unresectable locally advanced or metastatic pancreatic cancer. S-1 was
      administered orally twice daily. External-beam radiotherapy was delivered in
      fractions of 1.25 Gy x 2 per day, totalling 50 Gy per 40 fractions for 4 weeks. S
      1 was given at five dose levels: 60 mg m(-2) day(-1) on days 1-7 and 15-21 (level
      1), 1-14 (level 2), and 1-21 (level 3a) and 80 mg m(-2) day(-1) on days 1-21
      (level 3b) and 1-28 (level 4). We studied 17 patients: dose levels 1 (four
      patients), 2 (four patients), 3a (three patients), 3b (three patients), and 4
      (three patients). One patient in level 1 (grade 3 vomiting) and two patients in
      level 4 (grade 4 neutropenia and grade 3 anorexia) showed DLT. No DLT was seen
      for levels 2, 3a, and 3b. Clinical effects by computed tomography included 5
      partial responses (35%), 11 cases of stable disease, and one case of progressive
      disease. CA19-9 levels of less than half the starting values were observed in 8
      of 16 (50%) patients. S-1 at a dose of 80 mg m(-2) day(-1) given on days 1-21 is
      safe and recommended for phase-II study in patients with locally advanced and
      unresectable pancreatic cancer when given with EBRT.

PMID- 17437023
TI  - Hubs in biological interaction networks exhibit low changes in expression in
      experimental asthma.
AB  - Asthma is a complex polygenic disease involving the interaction of many genes. In
      this study, we investigated the allergic response in experimental asthma. First,
      we constructed a biological interaction network using the BOND (Biomolecular
      Object Network Databank) database of literature curated molecular interactions.
      Second, we mapped differentially expressed genes from microarray data onto the
      network. Third, we analyzed the topological characteristics of the modulated
      genes. Fourth, we analyzed the correlation between the topology and biological
      function using the Gene Ontology classifications. Our results demonstrate that
      nodes with high connectivity (hubs and superhubs) tend to have low levels of
      change in gene expression. The significance of our observations was confirmed by
      permutation testing. Furthermore, our analysis indicates that hubs and superhubs
      have significantly different biological functions compared with peripheral nodes
      based on Gene Ontology classification. Our observations have important
      ramifications for interpreting gene expression data and understanding biological
      responses. Thus, our analysis suggests that a combination of differential gene
      expression plus topological characteristics of the interaction network provides
      enhanced understanding of the biology in our model of experimental asthma.

PMID- 17437022
TI  - Chemo-hormone therapy of non-well-differentiated endocrine tumours from different
      anatomic sites with cisplatinum, etoposide and slow release lanreotide
      formulation.
AB  - We report the results of a phase II trial in patients with metastatic endocrine
      tumours from different sites, which aimed to evaluate the anti-tumour activity
      and toxicity of a cisplatinum and etoposide regimen administered in combination
      with the somatostatin agonist lanreotide given in slow release formulation.
      Between January 1999 and November 2003, 27 patients with histological diagnoses
      of endocrine tumours with different degrees of differentiation, excluding well
      differentiated carcinoid neoplasms, received intravenous (i.v.) administration of
      cisplatinum (30 mg m(-2)) and etoposide (100 mg m(-2)) on days 1-3 and
      intramuscular administration of 60 mg lanreotide on day 1, in a 21-day cycle. All
      of the patients were evaluable for toxicity and response. The treatment was very
      well tolerated as no grade 4 toxicity was observed. Four patients achieved a
      complete response, six a partial response, 12 experienced disease stabilisation
      and five disease progression. The average time to progression and to survival
      were 9 and 24 months respectively. These results suggest that this chemo-hormone
      therapy regimen is well tolerated and active in patients with non-well
      differentiated endocrine tumours.

PMID- 17437024
TI  - Flexibility in energy metabolism supports hypoxia tolerance in Drosophila flight
      muscle: metabolomic and computational systems analysis.
AB  - The fruitfly Drosophila melanogaster offers promise as a genetically tractable
      model for studying adaptation to hypoxia at the cellular level, but the metabolic
      basis for extreme hypoxia tolerance in flies is not well known. Using (1)H NMR
      spectroscopy, metabolomic profiles were collected under hypoxia. Accumulation of
      lactate, alanine, and acetate suggested that these are the major end products of
      anaerobic metabolism in the fly. A constraint-based model of ATP-producing
      pathways was built using the annotated genome, existing models, and the
      literature. Multiple redundant pathways for producing acetate and alanine were
      added and simulations were run in order to find a single optimal strategy for
      producing each end product. System-wide adaptation to hypoxia was then
      investigated in silico using the refined model. Simulations supported the
      hypothesis that the ability to flexibly convert pyruvate to these three by
      products might convey hypoxia tolerance by improving the ATP/H(+) ratio and
      efficiency of glucose utilization.

PMID- 17437025
TI  - Inferring condition-specific transcription factor function from DNA binding and
      gene expression data.
AB  - Numerous genomic and proteomic datasets are permitting the elucidation of
      transcriptional regulatory networks in the yeast Saccharomyces cerevisiae.
      However, predicting the condition dependence of regulatory network interactions
      has been challenging, because most protein-DNA interactions identified in vivo
      are from assays performed in one or a few cellular states. Here, we present a
      novel method to predict the condition-specific functions of S. cerevisiae
      transcription factors (TFs) by integrating 1327 microarray gene expression data
      sets and either comprehensive TF binding site data from protein binding
      microarrays (PBMs) or in silico motif data. Importantly, our method does not
      impose arbitrary thresholds for calling target regions 'bound' or genes
      'differentially expressed', but rather allows all the information derived from a
      TF binding or gene expression experiment to be considered. We show that this
      method can identify environmental, physical, and genetic interactions, as well as
      distinct sets of genes that might be activated or repressed by a single TF under
      particular conditions. This approach can be used to suggest conditions for
      directed in vivo experimentation and to predict TF function.

PMID- 17437026
TI  - A genome-scale computational study of the interplay between transcriptional
      regulation and metabolism.
AB  - This paper presents a new method, steady-state regulatory flux balance analysis
      (SR-FBA), for predicting gene expression and metabolic fluxes in a large-scale
      integrated metabolic-regulatory model. Using SR-FBA to study the metabolism of
      Escherichia coli, we quantify the extent to which the different levels of
      metabolic and transcriptional regulatory constraints determine metabolic
      behavior: metabolic constraints determine the flux activity state of 45-51% of
      metabolic genes, depending on the growth media, whereas transcription regulation
      determines the flux activity state of 13-20% of the genes. A considerable number
      of 36 genes are redundantly expressed, that is, they are expressed even though
      the fluxes of their associated reactions are zero, indicating that they are not
      optimally tuned for cellular flux demands. The undetermined state of the
      remaining approximately 30% of the genes suggests that they may represent
      metabolic variability within a given growth medium. Overall, SR-FBA enables one
      to address a host of new questions concerning the interplay between regulation
      and metabolism.

PMID- 17437027
TI  - Novel peptide identification from tandem mass spectra using ESTs and sequence
      database compression.
AB  - Peptide identification by tandem mass spectrometry is the dominant proteomics
      workflow for protein characterization in complex samples. Traditional search
      engines, which match peptide sequences with tandem mass spectra to identify the
      samples' proteins, use protein sequence databases to suggest peptide candidates
      for consideration. Although the acquisition of tandem mass spectra is not biased
      toward well-understood protein isoforms, this computational strategy is failing
      to identify peptides from alternative splicing and coding SNP protein isoforms
      despite the acquisition of good-quality tandem mass spectra. We propose, instead,
      that expressed sequence tags (ESTs) be searched. Ordinarily, such a strategy
      would be computationally infeasible due to the size of EST sequence databases;
      however, we show that a sophisticated sequence database compression strategy,
      applied to human ESTs, reduces the sequence database size approximately 35-fold.
      Once compressed, our EST sequence database is comparable in size to other
      commonly used protein sequence databases, making routine EST searching feasible.
      We demonstrate that our EST sequence database enables the discovery of novel
      peptides in a variety of public data sets.

PMID- 17437028
TI  - UV-B responsive microRNA genes in Arabidopsis thaliana.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs that play critical roles in post
      transcriptional gene regulation. In plants, mature miRNAs pair with complementary
      sites on mRNAs and subsequently lead to cleavage and degradation of the mRNAs.
      Many miRNAs target mRNAs that encode transcription factors; therefore, they
      regulate the expression of many downstream genes. In this study, we carry out a
      survey of Arabidopsis microRNA genes in response to UV-B radiation, an important
      adverse abiotic stress. We develop a novel computational approach to identify
      microRNA genes induced by UV-B radiation and characterize their functions in
      regulating gene expression. We report that in A. thaliana, 21 microRNA genes in
      11 microRNA families are upregulated under UV-B stress condition. We also discuss
      putative transcriptional downregulation pathways triggered by the induction of
      these microRNA genes. Moreover, our approach can be directly applied to miRNAs
      responding to other abiotic and biotic stresses and extended to miRNAs in other
      plants and metazoans.

PMID- 17437029
TI  - Pathway redundancy and protein essentiality revealed in the Saccharomyces
      cerevisiae interaction networks.
AB  - The biological interpretation of genetic interactions is a major challenge.
      Recently, Kelley and Ideker proposed a method to analyze together genetic and
      physical networks, which explains many of the known genetic interactions as
      linking different pathways in the physical network. Here, we extend this method
      and devise novel analytic tools for interpreting genetic interactions in a
      physical context. Applying these tools on a large-scale Saccharomyces cerevisiae
      data set, our analysis reveals 140 between-pathway models that explain 3765
      genetic interactions, roughly doubling those that were previously explained.
      Model genes tend to have short mRNA half-lives and many phosphorylation sites,
      suggesting that their stringent regulation is linked to pathway redundancy. We
      also identify 'pivot' proteins that have many physical interactions with both
      pathways in our models, and show that pivots tend to be essential and highly
      conserved. Our analysis of models and pivots sheds light on the organization of
      the cellular machinery as well as on the roles of individual proteins.

PMID- 17437030
TI  - Integrating scientific cultures.

PMID- 17437031
TI  - Do C-reactive protein levels help predict onset of rheumatoid arthritis in women?

PMID- 17437032
TI  - Nrf2/ARE regulated antioxidant gene expression in endothelial and smooth muscle
      cells in oxidative stress: implications for atherosclerosis and preeclampsia.
AB  - Increased generation of reactive oxygen species (ROS) in vascular diseases such
      as atherosclerosis, diabetes, chronic renal failure and preeclampsia readily
      leads to impaired endothelium-dependent relaxation and vascular injury. To
      counteract ROS- and electrophile-mediated injury, cells can induce a number of
      genes encoding phase II detoxifying enzymes and antioxidant proteins. A cis
      acting transcriptional regulatory element, designated as antioxidant response
      element (ARE) or electrophile response element (EpRE), mediates the
      transcriptional activation of genes such as heme oxygenase-1, gamma
      glutamylcysteine synthethase, thioredoxin reductase, glutathione-S-transferase
      and NAD(P)H:quinone oxidoreductase. Other antioxidant enzymes such as superoxide
      dismutase and catalase and non-enzymatic scavengers such as glutathione are also
      involved in scavenging ROS. Nuclear factor-erythroid 2-related factor 2 (Nrf2), a
      member of the Cap nno Collar family of basic region-leucine zipper (bZIP)
      transcription factors, plays an important role in ARE-mediated antioxidant gene
      expression. Kelch-like ECH-associated protein-1 (Keap1) normally sequesters Nrf2
      in the cytoplasm in association with the actin cytoskeleton, but upon oxidation
      of cysteine residues Nrf2 dissociates from Keap1, translocates to the nucleus and
      binds to ARE sequences leading to transcriptional activation of antioxidant and
      phase II detoxifying genes. Protein kinase C (PKC), mitogen-activated protein
      kinases (MAPKs) and phosphotidylinositol 3-kinase (PI3K) have been implicated in
      the regulation of Nrf2/ARE signaling. We here review the evidence that the
      Nrf2/ARE signaling pathway plays an important role in vascular homeostasis and
      the defense of endothelial and smooth muscle cells against sustained oxidative
      stress associated with diseases such as atherosclerosis and preeclampsia.

PMID- 17437033
TI  - Translating blood-borne stimuli: chemotransduction in the carotid body.
AB  - The carotid body can transduce hypoxia and other blood-borne stimuli, perhaps
      including hypoglycaemia, into afferent neural discharge that is graded for
      intensity and which forms the afferent limb of a cardiorespiratory and
      neuroendocrine reflex loop. Hypoxia inhibits a variety of K(+) channels in the
      type I cells of the carotid body, in a seemingly species-dependent manner, and
      the resultant membrane depolarisation is sufficient to activate voltage-gated
      Ca(2+) entry leading to neurosecretion and afferent discharge. The ion channels
      that respond to hypoxia appear to do so indirectly and recent work has therefore
      focussed upon identification of other proteins in the type I cells of the carotid
      body that may play key roles in the oxygen sensing process. Whilst a role for
      mitochondrial and/or NADPH-derived reactive oxygen species (ROS) has been
      proposed, the evidence for their signalling hypoxia in the carotid body is
      presently less than compelling and two alternate hypotheses are currently being
      tested further. The first implicates haemoxygenase 2 (HO-2), which may control
      specific K(+) channel activation through O(2)-dependent production of the
      signalling molecule, carbon monoxide. The second hypothesis suggests a role for
      the cellular energy sensor, AMP-activated protein kinase (AMPK), which can
      inhibit type I cell K(+) channels and increase afferent discharge when activated
      by hypoxia-induced elevations in the AMP: ATP ratio. The apparent richness of
      O(2)-sensitive K(+) channels and sensor mechanisms within this organ may indicate
      a redundancy system for this vital cellular process or it may be that each
      protein contributes differently to the overall response, for example, with
      different O(2) affinities. The mechanism by which low glucose is sensed is not
      yet known, but recent evidence suggests that it is not via closure of K(+)
      channels, unlike the hypoxia transduction process.

PMID- 17437034
TI  - H(2)S and cellular proliferation and apoptosis.
AB  - Hydrogen sulfide (H(2)S) is among a family of endogenous molecules of gas,
      defined as gasotransmitters. In recent years, endogenous production of H(2)S and
      its physiological importance have been realized. Abnormal metabolism and
      functions of H(2)S contribute to or participate in the pathogenesis of many
      diseases. This article reviews recent discoveries on the roles of H(2)S in the
      regulation of cell proliferation and apoptosis. The molecular mechanisms for the
      cellular effects of H(2)S are also recapitulated, including changes in mitogen
      activated protein kinase, cell cycle-related kinase, cell death-related gene and
      ion channels. A better understanding of H(2)S-regualted cell growth or death will
      pave way for future design of novel pharmacological and therapeutic interventions
      for various diseases.

PMID- 17437035
TI  - Effects of arachidonic acid metabolites on airway sensors.
AB  - Arachidonic acid (AA) in the cell membrane produces a variety of metabolites by
      different enzymatic pathways. These lipid metabolites, along with other
      mediators, play an important role in the inflammatory processes. Many of them can
      bind directly to the receptors on the sensory endings and initiate electrical
      impulses to be transmitted to the central nervous system, causing reflex
      responses. These bioactive AA metabolites may also alter the lung mechanics
      (mechanical environment of the sensory ending), and in turn, stimulate sensory
      afferents. In addition, some metabolites may sensitize the sensory endings and
      make them more responsive to other mechanical or chemical stimulation. These
      metabolites may also induce other mediators and modulators to cause physiological
      effects. Furthermore, some of them may attract inflammatory cells to produce a
      localized effect. In short, AA metabolites may come from different sources and
      act through multiple pathways to stimulate airway sensors. This brief review is
      intended to illustrate the underlying mechanisms and help elucidate the
      inflammatory process in the airways.

PMID- 17437036
TI  - Interleukin-6 protects cerebellar granule neurons from NMDA-induced
      neurotoxicity.
AB  - Interleukin-6 (IL-6) is an important cytokine that participates in inflammation
      reaction and cell growth and differentiation in the immune and nervous systems.
      However, the neuroprotection of IL-6 against N-methyl-D-aspartate (NMDA)-induced
      neurotoxicity and the related underlying mechanisms are still not identified. In
      the present study, the cultured cerebellar granule neurons (CGNs) from postnatal
      (8-day) infant rats were chronically exposed to IL-6 for 8 d, and then NMDA (100
      micromol/L) was applied to the cultured CGNs for 30 min. Methyl-thiazole
      tetrazolium (MTT) assay, terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling (TUNEL) method and confocal laser scanning microscope (CLSM) were
      used to detect neuronal vitality, apoptosis and dynamic changes of intracellular
      Ca(2+) levels in the neurons, respectively. Anti-gp130 monoclonal antibody (75
      ng/mL) was employed to the cultured CGNs with IL-6 to inhibit IL-6 activity so as
      to evaluate the role of gp130 (a 130 kDa glucoprotein transducing IL-6 signal) in
      mediating IL-6 neuroprotection. Western blot was used to measure the expressions
      of phospho-signal transducer and activator of transcription 3 (STAT3) and phospho
      extracellular signal regulated kinase 1/2 (ERK1/2) in the cultured CGNs. The NMDA
      stimulation of the cultured CGNs without IL-6 pretreatment resulted in a
      significant reduction of the neuronal vitality, notable enhancement of the
      neuronal apoptosis and intracellular Ca(2+) overload in the neurons. The NMDA
      stimulation of the CGNs chronically pretreated with IL-6 caused a remarkable
      increase in the neuronal vitality, marked suppression of neuronal apoptosis and
      intracellular Ca(2+) overload in the neurons, compared with that in the control
      neurons without IL-6 pretreatment. Furthermore, anti-gp130 antibody blocked the
      inhibitory effect of IL-6 on NMDA-induced intracellular Ca(2+) overload in the
      neurons. The levels of phospho-STAT3 and phospho-ERK1/2 were significantly higher
      in IL-6-pretreated CGNs than those in IL-6-untreated neurons. The results suggest
      that chronic IL-6 pretreatment of CGNs protects the neurons against NMDA-induced
      neurotoxicity. The neuroprotective effect of IL-6 is closely related to its
      suppression of NMDA-induced intracellular Ca(2+) overload and is possibly
      mediated by gp130/JAK-STAT3 and gp130/RAS-ERK1/2 transduction pathways.

PMID- 17437037
TI  - [Effect of opening of mitochondrial ATP-sensitive K(+) channels on the expression
      of hypoxia inducible factor-1alpha and cell proliferation in pulmonary arterial
      smooth muscle cells of rats].
AB  - The objective of this paper was to investigate the effect of mitochondrial ATP
      sensitive K(+) (MitoK(ATP)) channels on the expression of hypoxia inducible
      factor-1alpha (HIF-1alpha) and cell proliferation in pulmonary arterial smooth
      muscle cells (PASMCs) of rats. Cultured PASMCs were divided into six groups as
      follows: (1) normoxia group: cultured under normoxia for 24 h; (2) normoxia +
      diazoxide group: cultured under normoxia with diazoxide, an opener of MitoK(ATP)
      channel, for 24 h; (3) normoxia + 5-HD group: cultured under normoxia with 5
      hydroxydecanoate (5-HD), an antagonist of MitoK(ATP) channel, for 24 h; (4)
      hypoxia group: cultured under hypoxia (37 degrees C, 5% O(2), 5% CO(2), 90% N(2))
      for 24 h; (5) hypoxia + diazoxide group: cultured under hypoxia (37 degrees C, 5%
      O(2), 5% CO(2), 90% N(2)) with diazoxide for 24 h; (6) hypoxia + 5-HD group:
      cultured under hypoxia (37 degrees C, 5% O(2), 5% CO(2), 90% N(2)) with 5-HD for
      24 h. The relative changes in mitochondrial potential were tested with Rhodamine
      123 (R-123) fluorescence technique. Immunohistochemical method was used to trace
      the expression of HIF-1alpha. The proliferation of PASMCs was examined by MTT
      colorimetric assay. The results were as follows: The intensity of R-123
      fluorescence in normoxia + diazoxide group was significantly increased as
      compared with that in normoxia group (P<0.05), and the intensity of R-123
      fluorescence in hypoxia + diazoxide group was also significantly increased as
      compared with that in hypoxia group (P<0.05). 24-hour hypoxia or 24-hour hypoxia
      + diazoxide markedly increased the intensity of R-123 fluorescence in PASMCs as
      compared with normoxia (P<0.05), and the change was more prominant in hypoxia +
      diazoxide group than that in hypoxia group (P<0.05). There was no significant
      difference in the intensity of R-123 fluorescence between normoxia group and
      normoxia + 5-HD group (P>0.05). However, 5-HD weakened the effect of 24-hour
      hypoxia on the intensity of R-123 fluorescence. The intensity of R-123
      fluorescence in hypoxia + 5-HD group was significantly decreased as compared with
      that in hypoxia group (P<0.05). After exposure to hypoxia or hypoxia + diazoxide
      for 24 h, the expression of HIF-1alpha and the proliferation of PASMCs were
      significantly increased as compared with that in normoxia or normoxia + diazoxide
      group (P<0.05), and the change was more significant in hypoxia + diazoxide group
      than that in hypoxia group (P<0.05). There was no significant difference in the
      expression of HIF-1alpha and the proliferation of PASMCs between normoxia group
      and normoxia + 5-HD group (P>0.05). However, the expression of HIF-1alpha and the
      proliferation of PASMCs in hypoxia + 5-HD group were significantly decreased as
      compared with that in hypoxia group (P<0.05). All these results suggest that the
      opening of MitoK(ATP) channels followed by a depolarization of mitochondrial
      membrane might contribute to the increase of the expression of HIF-1alpha and the
      proliferation of PASMCs. This might be a mechanism of the development of hypoxic
      pulmonary hypertension.

PMID- 17437038
TI  - [Changes of vasoactive intestinal polypeptide and vasoactive intestinal
      polypeptide receptor 1 in small intestine and liver during macaque development].
AB  - The present study was aimed to investigate the changes of vasoactive intestinal
      polypeptide (VIP) and VIP receptor 1 (VIPR1) in small intestinal and hepatic
      tissues during macaque development. The tissue samples of small intestine, liver
      and blood samples from peripheral and portal vein of 4 macaques of 6-month fetus,
      2-day neonate, 45-day neonate and adult were obtained after anesthetization. The
      concentration of VIP in blood or tissues of macaques was measured by
      radioimmunoassay. The distribution of VIP in small intestinal or hepatic tissues
      was visualized by immunohistochemical staining. The expression of VIPR1 was
      detected by in situ hybridization. The results showed that: (1) VIP concentration
      in intestinal tissue of 6-month fetus was (20.7+/-14.3) ng/mg protein, and a few
      VIP-positive nerve fibers first appeared in intestinal villus root and submucosal
      layer but not in muscle layer. The intestinal concentration of VIP increased
      gradually with macaque development and reached (514.8+/- 49.2) ng/mg protein in
      adult, significantly higher than that in 6-month fetus (P<0.01). (2) In adult
      animal, VIP-positive nerve fibers became thicker and gradually extended into the
      mucosal crypt, submucosal layer nerve, myenteric nerve plexus of annular muscle
      and indulge muscle, and annular muscle. Correspondingly, the expression of VIPR1
      in intestine was up-regulated during development. (3) On the contrary, the levels
      of VIP and VIPR1 in liver were gradually decreased during development. (4) VIP
      concentration in small intestinal tissue was higher than that in hepatic tissue
      during development. The VIP level in portal vein was also significantly higher
      than that in peripheral blood during development. In conclusion, the levels of
      VIP and VIPR1 in mucosal crypt, submucosal layer nerve, myenteric nerve plexus of
      annular muscle and indulge muscle increase rapidly after birth. Most of VIP from
      intestinal tract is degraded in portal vein before entering liver, suggesting
      that VIP does not metabolize and decompose in liver, and that VIPR1 is only
      present in embryo hepatic blood vessels.

PMID- 17437039
TI  - Recombinant soluble receptor activator of nuclear factor-kappaB inhibits
      parathyroid hormone-induced osteoclastogenesis in vitro.
AB  - The recent identification of receptor activator of nuclear factor-kappaB ligand
      (RANKL)/RANK/osteoprotegerin (OPG) cytokine system has led to a new molecular
      perspective on osteoclast biology and bone homeostasis. Specifically, the
      interaction between RANKL and RANK is responsible for osteoclast differentiation.
      In the present study, we evaluated whether soluble RANK (sRANK) could act as an
      antagonist of RANKL and down-regulate osteoclastogenesis and bone resorption in
      vitro. The prokaryotic expression vector coding for sRANK was constructed. Then
      the construct was introduced into E. coli Origami B (DE3) competent cells and
      recombinant sRANK was successfully produced and purified through affinity
      chromatography. sRANK reduced osteoclast-like cell (OLC) formation and resorption
      pit formation induced by parathyroid hormone (PTH) in a dose-dependent manner. In
      addition, sRANK significantly inhibited PTH-induced mRNA expression of carbonic
      anhydrase II and tartrate-resistant acid phosphatase in murine bone marrow cells
      as confirmed by using semi-quantitative RT-PCR. The down-regulation was highly
      correlated with the effect of sRANK on OLC formation from marrow cells. These
      data demonstrate the anti-resorptive effects of sRANK in vitro and highlight the
      potential of sRANK as a novel therapeutic approach to bone disorders
      characterized by enhanced bone resorption.

PMID- 17437040
TI  - alpha1-adrenergic receptors activate AMP-activated protein kinase in rat hearts.
AB  - To test the hypothesis that AMP-activated protein kinase (AMPK) is possibly the
      downstream signaling molecule of certain subtypes of adrenergic receptor (AR) in
      the heart, we evaluated AMPK activation mediated by ARs in H9C2 cells, a rat
      cardiac source cell line, and rat hearts. The AMPK-alpha subunit and the
      phosphorylation level of Thr(172)-AMPK-alpha subunit were subjected to Western
      blot analysis. Osmotic minipumps filled with norepinephrine (NE), phenylephrine
      (PE) or vehicle [0.01% (W/V) vitamin C solution] were implanted into male Sprague
      Dawley rats subcutaneously. The pumps delivered NE or PE continuously at the rate
      of 0.2 mg/kg per hour. After 7-day infusion, the activity of AMPK was examined
      following immunoprecipitation with anti-AMPK-alpha antibody. At the cellular
      level, we found that NE elevated AMPK phosphorylation level in a dose- and time
      dependent manner, with the maximal effect at 10 micromol/L NE after 10-minute
      treatment. This effect was insensitive to propranolol, a specific beta-AR
      antagonist, but abolished by prazosin, an alpha(1)-AR antagonist, suggesting that
      alpha(1)-AR but not beta-AR mediated the phosphorylation of AMPK. Moreover, the
      results from rat models of 7-day-infusion of AR agonists demonstrated that the
      activity of AMPK was significantly higher in NE (7.4-fold) and PE (6.0-fold)
      infusion groups than that in the vehicle group (P<0.05, n=6). On the other hand,
      no obvious cardiac hypertrophy and tissue fibrosis changes were observed in PE
      infused rats. Taken together, our results demonstrate that alpha(1)-AR
      stimulation enhances the activity of AMPK, indicating an important role of
      alpha(1)-AR stimulation in the regulation of AMPK in the heart. Understanding the
      activation of AMPK mediated by alpha(1)-AR might have clinical implications in
      the therapy of heart failure.

PMID- 17437041
TI  - Changes in the firing activity of serotonergic neurons in the dorsal raphe
      nucleus in a rat model of Parkinson's disease.
AB  - In the present study, changes in the neuronal activity of serotonergic neurons in
      the dorsal raphe nucleus (DRN) and the effect of the selective 5-HT(1A) receptor
      antagonist WAY-100635 in a rat model of Parkinson's disease (PD) were
      investigated by using extracellular single unit recording. Rat model of PD was
      produced by microinjection of 6-hydroxydopamine (6-OHDA) into the substantia
      nigra pars compacta on the right side of the brain. The results showed that the
      mean spontaneous firing rate of DRN serotonergic neurons in the control and 6
      OHDA-lesioned rats were (1.76+/-0.11) spikes/s (n=24) and (2.43+/-0.17) spikes/s
      (n=21), respectively. The firing rate of serotonergic neurons in 6-OHDA-lesioned
      rats was significantly higher than that in the control rats (P<0.001). In the
      control rats, 92% (22/24) of the neurons fired regularly and 8% (2/24) fired in
      bursts. In rats with 6-OHDA lesions, 9% (2/21) of neurons fired regularly, 43%
      (9/21) exhibited irregular pattern and 48% (10/21) fired in bursts. The
      percentage of DRN serotonergic neurons firing in bursts was obviously higher in 6
      OHDA-lesioned rats than that in the control rats (P<0.001). Local injection of
      WAY-100635 (3 microg in 200 nL) into the DRN significantly increased the firing
      rate of serotonergic neurons with no change in firing pattern in the control rats
      (n=19, P<0.002), but did not change the firing rate and firing pattern of
      serotonergic neurons in 6-OHDA-lesioned rats (n=17, P>0.05). These results
      suggest the dysfunction of 5-HT(1A) receptor in 6-OHDA-lesioned rats and the
      involvement of the DRN in the pathophysiological mechanism of PD.

PMID- 17437042
TI  - [Changes of bone morphogenetic protein-7 and inhibitory Smad expression in
      streptozotocin-induced diabetic nephropathy rat kidney].
AB  - The present study was designed to observe the expressions of bone morphogenetic
      protein-7 (BMP-7) and inhibitory Smads in kidney of rats with diabetic
      nephropathy (DN), and explore the possible mechanism of DN. Male Wistar rats
      weighing 180-220 g were single injected with streptozocin (STZ, 55 mg/kg body
      weight) for 2, 4, 8 and 16 weeks to induce DN. Blood glucose, kidney weight/body
      weight and 24-hour urine protein in the control and DN rats were examined; the
      expressions of BMP-7, Smad6 and Smad7 were detected by using immunohistochemical
      techniques, Western blot and real-time PCR. The results showed that blood glucose
      and 24-hour urine protein in DN rats were higher than that in the control rats
      and kidney weight/body weight was also elevated in DN rats, especially in 16-week
      STZ-induced rats. The expressions of BMP-7 and Smad6 proteins in DN rats were
      elevated, while BMP-7 mRNA expression was increased 2 weeks after STZ injection
      and decreased 16 weeks after STZ injection. The expressions of Smad7 protein and
      mRNA were elevated in DN rats 2 weeks after STZ injection and decreased 16 weeks
      after STZ injection. In addition, the expressions of transforming growth factor
      beta1 (TGF-beta1) and collagen type I (COL-I) mRNA were increased in DN rats.
      These results suggest in the early stage of DN, increase in BMP-7 and inhibitory
      Smad expression may play a role in the feedback regulation and restrain the
      development of DN.

PMID- 17437043
TI  - [Spatial-temporal distribution of glycogen synthase kinase 3beta and adenomatous
      polyposis coli protein are involved in the injury and repair of airway epithelial
      cells induced by scratching].
AB  - To investigate the roles of glycogen synthase kinase 3beta (GSK3beta) and
      adenomatous polyposis coli (APC) protein in wound repair of airway epithelial
      cells (AECs), we established a wound model of airway epithelium in vitro. Then
      the following tests were undertaken: (1) Western blot was used to detect the
      levels of total GSK3beta and phosphorylated GSK3beta in human bronchial
      epithelial (16HBE) cells; (2) The localizations of APC protein was observed by
      using immunofluorescence technique; (3) Immunoprecipitation was used to
      investigate the relationship between APC protein and GSK3beta during the repair
      of 16HBE cells. The results were as follows: (1) The level of phosphorylated
      GSK3beta increased 0.5 h after scratching (P<0.05), reached a maximum at 6 h
      (P<0.05), and maintained until 12 h, while the total level of GSK3beta remained
      constant; (2) Results of immunofluorescence study showed that APC protein
      clustered with tubulin in the region of the migrating leading cells 6 h after
      scratching, which was dissimilar with that in the cells 0 h after scratching; (3)
      GSK3beta and APC protein were immunoprecipitated and analysed on SDS-PAGE. We
      found that GSK3beta and APC protein were precipitated, indicating that the two
      proteins existed in a complex. After scratching, dissociation of the two proteins
      occurred. Taken together, we conclude that scratching caused a decrease in
      phosphorylation of GSK3beta, and that reduced phosphorylation of GSK3beta
      promoted APC protein to bind to the plus ends of microtubules and stabilize the
      growing ends. These observations suggest that APC protein and GSK3beta may
      synergistically play an important role in the repair of airway epithelium.

PMID- 17437044
TI  - Glycogen synthase kinase 3beta induces cell cycle arrest in a cyclin D1-dependent
      manner in human lung adenocarcinoma cell line A549.
AB  - The effect of glycogen synthase kinase 3beta (GSK3beta) has been repeatedly
      implicated in cell proliferation, but studies on the effect of GSK3beta in
      different cell lines with different stimuli have drawn different conclusions. To
      investigate the direct effect of GSK3beta on cell growth in human lung
      adenocarcinoma cell line A549, we changed its activity by transient transfection
      with two kinds of GSK3beta mutant plasmids, constitutively active form S9A
      GSK3beta and dominant negative form KM-GSK3beta. Twenty-four hours later, cell
      counting, flow cytometry and Western blot detection were made respectively. The
      results showed that enhancing GSK3beta activity caused a decrease in cell number,
      as well as a higher percentage of cells at G(1) phase. Further, the expression of
      cyclin D1 was down-regulated by GSK3beta. Taken together, our observations
      suggest that GSK3beta may induce G(1) cell cycle arrest in a cyclin D1-dependent
      fashion and therefore possibly plays a growth-inhibitory role in A549 cells.

PMID- 17437045
TI  - [Changes of intermedin/adrenomedullin 2 and its receptors in the right ventricle
      of rats with chronic hypoxic pulmonary hypertension].
AB  - The purpose of the present study was to explore the expression changes of
      intermedin/adrenomedullin 2 (IMD/ADM2), a novel small molecular bioactive
      peptide, and its receptors, calcitonin receptor-like receptor (CRLR) and receptor
      activity modifying proteins (RAMP1, RAMP2, RAMP3) in the right ventricle of rats
      with chronic hypoxia-induced pulmonary hypertension. Twenty male Sprague-Dawley
      rats were randomly divided into 4-week hypoxia group and normal control group
      (each n=10). The rats in hypoxia group were placed in an isobaric hypoxic
      chamber, in which O(2) content was maintained at 9%-11% by delivering N(2), and
      CO(2) content was maintained at <3% for 4 weeks (8 h/d, 6 d/week). The rats in
      the control group were housed in room air. The protein levels of IMD/ADM2 and
      adrenomedullin (ADM) in blood plasma and right ventricular tissue were measured
      by radioimmunoassay. The mRNA expressions of IMD/ADM2, ADM and their receptors
      CRLR, RAMP1, RAMP2, RAMP3 in right ventricular tissue were determined by reverse
      transcription-polymerase chain reaction (RT-PCR). The results showed that the
      ratio of right ventricle weight to left ventricle plus septum weight [RV/(LV+S)]
      and mean pulmonary arterial pressure (mPAP) were higher in hypoxia group than
      those in the control group (all P<0.01), suggesting that the rat model of
      pulmonary hypertension was successfully established. However, the mean carotid
      arterial pressure (mCAP) between the two groups had no significant difference.
      Compared with that in the control group, ADM contents in plasma and right
      ventricular tissue in hypoxia group increased by 1.26 and 1.68 folds (all
      P<0.01), respectively. Likewise, IMD/ADM2 contents in blood plasma and right
      ventricular tissue in hypoxia group increased by 0.90 and 1.19 folds (P<0.01),
      respectively, compared with that in the control group. The data of RT-PCR showed
      that mRNA levels of ADM, IMD/ADM2 and RAMP2 in hypoxia group increased by 155.1%
      (P<0.01), 80.9% (P<0.01) and 52.9% (P<0.05), respectively, compared with those in
      the control group. There were no significant differences in mRNA expressions of
      CRLR, RAMP1 and RAMP3 between the two groups (all P>0.05). Taken together, the
      results show that the level of IMD/ADM2 increases in the rats with chronic
      hypoxia-induced pulmonary hypertension.

PMID- 17437046
TI  - Electrophysiological effects of hydrogen sulfide on guinea pig papillary muscles
      in vitro.
AB  - The cardiac electrophysiological effects of hydrogen sulfide (H2S) were examined
      in guinea pig papillary muscles in vitro using intracellular microelectrode
      technique. The results obtained were as follows: (1) the duration of action
      potential (APD) in the normal papillary muscles was decreased by NaHS (H(2)S
      donor, 50, 100, 200 micromol/L) in a concentration-dependent manner; (2) in
      partially depolarized papillary muscles, 100 micromol/L NaHS not only reduced
      APD, but also decreased the amplitude of action potential (APA), overshoot (OS)
      and maximal velocity of depolarization at phase 0 (V(max)); (3) pretreatment with
      ATP-sensitive K(+) (K(ATP)) channel blocker glibenclamide (20 micromol/L)
      partially blocked the effects of NaHS (100 micromol/L); (4) pretreatment with L
      type Ca(2+) channel agonist Bay K8644 (0.5 micromol/L) also partially blocked the
      effects of NaHS (100 micromol/L); (5) pretreatment with Ca(2+)-free Krebs
      Henseleit solution containing glibenclamide (20 micromol/L) completely blocked
      the effects of NaHS (100 micromol/L); (6) APD in the normal papillary muscles was
      increased by DL-propargylglycine (PPG, an inhibitor of cystathionine gamma-lyase,
      200 micromol/L). All these results suggest that the electrophysiological effects
      of H(2)S on papillary muscles in our study are due to an increase in potassium
      efflux through the opening of K(ATP) channels and a decrease in calcium influx.
      Endogenous H(2)S may act as an important regulator in electrophysiological
      characters in papillary muscles.

PMID- 17437047
TI  - Down-regulation of perlecan expression contributes to the inhibition of rat
      cardiac microvascular endothelial cell proliferation induced by hypoxia.
AB  - Exposure of endothelial cells (ECs) to hypoxia leads to a decrease in EC
      proliferation. However, the mechanism by which hypoxia inhibits EC proliferation
      is unclear. Perlecan has been reported to play an important role in regulating EC
      proliferation. We hypothesized that perlecan was involved in the hypoxia-induced
      inhibition of EC proliferation. To test this hypothesis, rat cardiac
      microvascular ECs were cultured under normoxic or hypoxic conditions for 12 h and
      harvested for determination of perlecan mRNA expression using real-time reverse
      transcription-polymerase chain reaction (RT-PCR). The results showed that
      exposure of ECs to hypoxia for 12 h induced a decrease in perlecan mRNA
      expression (61.72%, P<0.05). Concomitantly, the down-regulation of endogenous
      perlecan induced by hypoxia or the neutralization of endogenous perlecan with
      anti-perlecan antibody significantly inhibited EC proliferation and
      responsiveness to basic fibroblast growth factor (bFGF), and decreased focal
      adhesion kinase (FAK) expression and extracellular signal-regulated kinase 1/2
      (ERK1/2) activation. These data indicate that down-regulation of perlecan
      expression contributes to hypoxia-induced inhibition of rat cardiac microvascular
      EC proliferation by suppressing FAK-mediated and ERK1/2-dependent growth signals.

PMID- 17437048
TI  - [Effect of hypoxia on the gene profile of human bone marrow-derived mesenchymal
      stem cells].
AB  - Our previous study demonstrates that hypoxia promotes human bone marrow-derived
      mesenchymal stem cell (hMSC) proliferation. The aim of the present study was to
      investigate the gene profile involved in this process by using cDNA microarray.
      Cultured hMSCs were treated with hypoxia (3% O(2)) for 4 h, 12 h, 24 h, 36 h, 48
      h and 72 h, respectively. Then these cells were collected to prepare total RNA.
      Hypoxia-induced gene expression profile was examined and analyzed by GenePix Pro
      4.0 software. Some of cDNA microarray results were confirmed by RT-PCR.
      Microarray analysis identified that 282 genes expressed differentially, of which
      most were involved in metabolism. The number of differentially expressed genes at
      different hypoxia time points was different, and most genes were regulated after
      24-hour hypoxia. Among the 282 differentially expressed genes, 4 hypoxia
      inducible factor 1 (HIF-1) targeted genes and 10 genes that changed at 3
      continuous time points were found. The results obtained indicated that 4 HIF-1
      targeted genes, i.e., transforming growth factor beta3 (TGFbeta3), phospho
      glycerate kinase 1 (PGK1), insulin-like growth factor binding protein 3 (IGFBP3)
      and BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), displayed up
      regulated pattern at 36 h under hypoxia. BNIP3 displayed a dynamically up
      regulated pattern at 12, 36 and 72 h under hypoxia. However, TGFbeta3 and PGK1
      were down-regulated at 72 h. In addition, the gene expressions of adenylate
      kinase 3-like 1 (HAC), neurofilament light polypeptide 68 kDa (NEFL), N-myc
      downstream regultated gene 1 (NDRG1), discoidin domain receptor family member 1
      (DDR1), tribbles homolog 3 (TRIB3), nucleoprotein (AHNAK) and eukaryotic
      elongation factor selenocyteine-tRNA-specific (EESTS) were up-regulated.
      Moreover, the gene expressions of EESTS, NEFL were up-regulated at 5 different
      time points under hypoxia. Furthermore, it was found that the gene expressions of
      histone cluster 1 (HIS1) and transferring receptor (TFRC) were down-regulated.
      These results suggest that the proliferation of hMSCs induced by hypoxia is a
      complex process in which a number of genes may be involved.

PMID- 17437049
TI  - [Low extracellular pH increases the persistent sodium current in guinea pig
      ventricular myocytes].
AB  - Whole-cell and cell-attached patch-clamp techniques were used to record the
      changes of persistent sodium current (I(Na.P)) in ventricular myocytes of guinea
      pig to investigate the effect of low extracellular pH on I(Na.P) and its
      mechanism. The results showed that low extracellular pH (7.0, 6.8 and 6.5)
      obviously increased the amplitude of whole-cell I(Na.P) in a [H(+)] concentration
      dependent manner. Under the condition of extracellular pH 6.5, I(Na.P) was
      markedly augmented from control (pH 7.4) value of (0.347+/-0.067) pA/pF to
      (0.817+/- 0.137) pA/pF (P<0.01, n=6), whereas the reducing agent dithiothreitiol
      (DTT, 1 mmol/L) reversed the increased IN(Na.P) from (0.817+/-0.137) pA/pF to
      (0.233+/-0.078) pA/pF (P<0.01 vs pH 6.5, n=6). Decreasing extracellular pH to 6.5
      also increased the persistent sodium channel activity in cell-attached patches.
      The mean open probability and mean open time were increased from control value of
      0.021+/-0.007 and (0.899+/-0.074) ms to 0.205+/-0.023 and (1.593+/-0.158) ms,
      respectively (both P<0.01, n=6), and such enhancement was reversed by application
      of 1 mmol/L DTT [to 0.019+/-0.005 and (0.868+/-0.190) ms, both P<0.01 vs pH 6.5,
      n=6]. Furthermore, protein kinase C (PKC) inhibitor bisindolylmaleimide (BIM, 5
      micromol/L) reduced the enhanced mean open probability and mean open time at pH
      6.5 from 0.214+/-0.024 and (1.634+/-0.137) ms to 0.025+/-0.006 and (0.914+/
      0.070) ms, respectively (both P<0.01 vs pH 6.5, n=6). The results demonstrate
      that low extracellular pH markedly increases I(Na.P) in guinea pig ventricular
      myocytes, in which activation of PKC may be involved.

PMID- 17437050
TI  - [Decreased A-type potassium current mediates the hyperexcitability of nociceptive
      neurons in the chronically compressed dorsal root ganglia].
AB  - The excitability of nociceptive neurons increases in the intact dorsal root
      ganglion (DRG) after a chronic compression, but the underlying mechanisms are
      still unclear. The aim of this study was to investigate the ionic mechanisms
      underlying the hyperexcitability of nociceptive neurons in the compressed
      ganglion. Chronic compression of DRG (CCD) was produced in adult rats by
      inserting two rods through the intervertebral foramina to compress the L4 DRG and
      the ipsilateral L5 DRG. After 5-7 d, DRG somata were dissociated and placed in
      culture for 12-18 h. In sharp electrode recording model, the lower current
      threshold and the depolarized membrane potential in the acutely dissociated CCD
      neurons were detected, indicating that hyperexcitability is intrinsic to the
      soma. Since voltage-gated K(+) (Kv) channels in the primary sensory neurons are
      important for the regulation of excitability, we hypothesized that CCD would
      alter K(+) current properties in the primary sensory neurons. We examined the
      effects of 4-aminopyridine (4-AP), a specific antagonist of A-type potassium
      channel, on the excitability of the control DRG neurons. With 4-AP in the
      external solution, the control DRG neurons depolarized (with discharges in some
      cells) and their current threshold decreased as the CCD neurons demonstrated,
      indicating the involvement of decreased A-type potassium current in the
      hyperexcitability of the injured neurons. Furthermore, the alteration of A-type
      potassium current in nociceptive neurons in the compressed ganglion was
      investigated with the whole-cell patch-clamp recording model. CCD significantly
      decreased A-type potassium current density in nociceptive DRG neurons. These data
      suggest that a reduction in A-type potassium current contributes, at least in
      part, to the increase in neuron excitability that may lead to the development of
      pain and hyperalgesia associated with CCD.

PMID- 17437051
TI  - Dissipation and residues of spinosad in eggplant and soil.

PMID- 17437052
TI  - Application of Aspergillus fumigatus xylanase for quality improvement of waste
      paper pulp.

PMID- 17437053
TI  - Enhancement of lead uptake by hyperaccumulator plant species Sedum alfredii hance
      using EDTA and IAA.

PMID- 17437054
TI  - Obstructive suburethral mass after transurethral injection of
      dextranomer/hyaluronic acid copolymer.
AB  - Dextranomer/hyaluronic acid copolymer (Zuidex(R)) is a new bulking agent. There
      is little data about the complications of using this substance as urethral
      bulking agent for the treatment of urinary stress incontinence. We are presenting
      a 59-year-old female patient who developed a suburethral mass and urinary
      retention after zuidex urethral injection. A stepwise approach for treatment was
      followed. Complete excision of the mass was the only curative procedure that
      succeeded.

PMID- 17437055
TI  - An 11-bp duplication in the promoter region of the VHL gene in a patient with
      cerebellar hemangioblastoma and renal oncocytoma.
AB  - Central nervous system hemangioblastomas are benign vascular tumours that may
      present sporadically or as manifestation of the von Hippel-Lindau (VHL) disease.
      VHL Syndrome is a rare autosomal dominant disorder characterized, besides
      hemangioblastomas, by susceptibility to multifocal and bilateral renal cell
      carcinoma and cysts, retinal angiomas, pheochromocytoma, epididymis cystoadenoma,
      pancreatic cysts and/or islet cell tumours. Germline mutations of VHL tumour
      suppressor gene cause the VHL disease, while somatic mutations have been
      associated with sporadic hemangioblastomas and clear-cell renal carcinomas. We
      identified an 11-bp duplication in the promoter region of the VHL gene in a VHL
      affected individual. Functional analysis revealed that this variant affects the
      binding or the binding affinity of one or more transcription factors that
      regulate the transcription of VHL in vivo, reducing the endogenous levels of VHL
      mRNA. Moreover, consistent with the "two hits" model, microsatellite analysis of
      hemangioblastoma tissue from this patient revealed Allelic Imbalance for the
      chromosomal region near the VHL gene. We propose that these molecular events,
      through a loss of pVHL function, lead to the onset of the VHL-related tumours in
      that individual.

PMID- 17437056
TI  - Human xylosyltransferases in health and disease.
AB  - The xylosyltransferases I and II (XT-I, XT-II, EC 2.4.2.26) catalyze the transfer
      of xylose from UDP-xylose to selected serine residues in the proteoglycan core
      protein, which is the initial and ratelimiting step in glycosaminoglycan
      biosynthesis. Both xylosyltransferases are Golgi-resident enzymes and transfer
      xylose to similar core proteins acceptors. XT-I and XT-II are differentially
      expressed in cell types and tissues, although the reason for the existence of two
      xylosyltransferase isoforms in all higher organisms remains elusive. Serum
      xylosyltransferase activity was found to be a biochemical marker for the
      assessment of disease activity in systemic sclerosis and for the diagnosis of
      fibrotic remodeling processes. Furthermore, sequence variations in the XT-I and
      XT-II coding genes were identified as risk factors for diabetic nephropathy,
      osteoarthritis or pseudoxanthoma elasticum. These findings point to the important
      role of the xylosyltransferases as disease modifiers in pathologies which are
      characterized by an altered proteoglycan metabolism. The present review discusses
      recent advances in mammalian xylosyltransferases and the impact of
      xylosyltransferases in proteoglycan-associated diseases.

PMID- 17437057
TI  - Glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated
      receptors.
AB  - Glycogen synthase 2 (Gys-2) is the ratelimiting enzyme in the storage of glycogen
      in liver and adipose tissue, yet little is known about regulation of Gys-2
      transcription. The peroxisome proliferator-activated receptors (PPARs) are
      transcription factors involved in the regulation of lipid and glucose metabolism
      and might be hypothesized to govern glycogen synthesis as well. Here, we show
      that Gys-2 is a direct target gene of PPARalpha, PPARbeta/delta and PPARgamma.
      Expression of Gys-2 is significantly reduced in adipose tissue of PPARalpha-/-,
      PPARbeta/delta-/- and PPARgamma+/- mice. Furthermore, synthetic PPARbeta/delta,
      and gamma agonists markedly up-regulate Gys-2 mRNA and protein expression in
      mouse 3T3-L1 adipocytes. In liver, PPARalpha deletion leads to decreased glycogen
      levels in the refed state, which is paralleled by decreased expression of Gys-2
      in fasted and refed state. Two putative PPAR response elements (PPREs) were
      identified in the mouse Gys-2 gene: one in the upstream promoter (DR-1prom) and
      one in intron 1 (DR-1int). It is shown that DR-1int is the response element for
      PPARs, while DR-1prom is the response element for Hepatic Nuclear Factor 4 alpha
      (HNF4alpha). In adipose tissue, which does not express HNF4alpha, DR-1prom is
      occupied by PPARbeta/delta and PPARgamma, yet binding does not translate into
      transcriptional activation of Gys-2. Overall, we conclude that mouse Gys-2 is a
      novel PPAR target gene and that transactivation by PPARs and HNF4alpha is
      mediated by two distinct response elements.

PMID- 17437058
TI  - Targeted inhibition of Livin resensitizes renal cancer cells towards apoptosis.
AB  - Cancer cells are typically characterized by apoptosis deficiency. In order to
      investigate a possible role for the anti-apoptotic livin gene in renal cell
      cancer (RCC), we analyzed its expression in tumor tissue samples and in RCC
      derived cell lines. In addition, we studied the contribution of livin to the
      apoptotic resistance of RCC cells by RNA interference (RNAi). Livin gene
      expression was detected in a significant portion of RCC tumor tissue specimens
      (13/14, 92.9%) and tumor-derived cell lines (12/15, 80.0%). Moreover, targeted
      inhibition of livin by RNAi markedly sensitized RCC cells towards proapoptotic
      stimuli, such as UV irradiation or the chemotherapeutic drugs etoposide, 5
      fluorouracil, and vinblastine. These effects were specific for livin expressing
      tumor cells. We conclude that livin can contribute significantly to the apoptosis
      resistance of RCC cells. Targeted inhibition of livin could represent a novel
      therapeutic strategy to increase the sensitivity of renal cancers towards pro
      apoptotic agents.

PMID- 17437059
TI  - Structure and function of bacterial cold shock proteins.
AB  - Cold shock proteins (Csps) comprise a family of small proteins that are
      structurally highly conserved and bind to single-stranded nucleic acids via their
      nucleic acid binding motifs RNP1 and RNP2. Bacterial Csps are mainly induced
      after a rapid temperature downshift to regulate the adaptation to cold stress,
      but are also present under normal conditions to regulate other biological
      functions. The structural unit characteristic for Csps occurs also as a cold
      shock domain (CSD) in other proteins and can be found in wide variety of
      organisms from bacteria to vertebrates. Important examples are the Y-box proteins
      that are known to be involved in regulation of several transcription and
      translation processes. This review describes the role of Csps in protein
      expression during cold shock with special emphasis on structural aspects of Csps.

PMID- 17437060
TI  - Retrospective analysis of etiopathogenesis of all cases of endophthalmitis at a
      large tertiary referral center.
AB  - PURPOSE: To report a large, consecutive series of endophthalmitis of all causes
      managed at a tertiary referral retina center. METHODS: Retrospective chart review
      of all cases diagnosed with endophthalmitis that received reatment and follow-up
      between January 2000 and January 2005. RESULTS: A total of 67 patients were
      diagnosed with endophthalmitis. The most common cause was postoperative
      endopthalmitis after cataract surgery. Initial management was vitreous needle
      biopsy with intravitreal antimicrobial injection in a majority of cases (79%).
      Vitreous cultures were positive in 32 eyes (44.4%); the most common isolate was
      coagulase negative Staphylococci. Final visual acuity was improved in 61% of
      patients. More than a third (38%) had vision worse than count fingers. Twenty
      eight eyes (39%) needed pars plana vitrectomy for secondary complications as a
      consequence of endophthalmitis. CONCLUSIONS: Cataract surgery remains the most
      common cause of endophthalmitis in this large tertiary referral retina center.
      Endophthalmitis resolved with vitreous needle biopsy and intravitreal injections
      in more than half of the cases. However, more than a third of patients required
      additional vitreoretinal surgery for secondary complications. More than a third
      of patients had nonfunctional vision after the resolution of endophthalmitis,
      which highlights the severity of this condition in the current expanding era of
      office-based intravitreal pharmacotherapy for retinal diseases.

PMID- 17437061
TI  - Vogt-Koyanagi-Harada disease in elderly Japanese patients.
AB  - PURPOSE: The purpose of this study was to evaluate the characteristics of Vogt
      Koyanagi-Harada (VKH) disease in elderly (age > or =65 years) Japanese patients.
      METHODS: We reviewed the medical records of all patients diagnosed with VKH
      disease at the Department of Ophthalmology, Oita University Hospital between
      October 1982 and March 2005. Data extracted included age, gender, prodromal
      symptoms, visual acuity, ocular manifestations, extraocular findings, human
      leukocyte antigen (HLA), ocular complications, treatment, and smoldering
      inflammation. RESULTS: Of the 68 patients with VKH disease, seven (10%) were
      classified as elderly at onset. The incidence of optic disk hyperemia, choroidal
      detachment, and cataract was significantly higher in the elderly patients than
      the non-elderly patients (<65 years). The total dose of corticosteroid used was
      higher in the elderly. The incidence of smoldering inflammation was more frequent
      in the elderly. Final visual acuity was preserved relatively well in the elderly.
      CONCLUSION: The significantly higher incidence of optic disk hyperemia, choroidal
      detachment, and cataract, and the more frequent smoldering inflammation in
      elderly VKH patients indicate that special attention should be paid to these
      parameters in elderly patients.

PMID- 17437062
TI  - Vogt-Koyanagi-Harada disease presenting as optic neuritis.
AB  - Vogt-Koyanagi-Harada (VKH) disease is a granulomatous multisystem inflammatory
      disorder that classically affects the uvea, inner ear, meninges, and skin. We
      report three patients who presented with initial findings suggestive of bilateral
      optic neuritis requiring CSF analysis and brain images. None of these patients
      had extraocular changes. Fluorescein angiography of the retina led to the
      diagnosis of VKH disease in all patients. Vogt-Koyanagi-Harada disease should be
      included in differential diagnosis of bilateral optic neuritis, even when
      extraocular manifestations of the disease are absent. In such cases, fluorescein
      angiography will aid diagnosis.

PMID- 17437063
TI  - A functional genomics approach to (iso)flavonoid glycosylation in the model
      legume Medicago truncatula.
AB  - Analysis of over 200,000 expressed sequence tags from a range of Medicago
      truncatula cDNA libraries resulted in the identification of over 150 different
      family 1 glycosyltransferase (UGT) genes. Of these, 63 were represented by full
      length clones in an EST library collection. Among these, 19 gave soluble proteins
      when expressed in E. coli, and these were screened for catalytic activity against
      a range of flavonoid and isoflavonoid substrates using a high-throughput HPLC
      assay method. Eight UGTs were identified with activity against isoflavones,
      flavones, flavonols or anthocyanidins, and several showed high catalytic
      specificity for more than one class of (iso)flavonoid substrate. All tested UGTs
      preferred UDP-glucose as sugar donor. Phylogenetic analysis indicated that the
      Medicago (iso)flavonoid glycosyltransferase gene sequences fell into a number of
      different clades, and several clustered with UGTs annotated as glycosylating non
      flavonoid substrates. Quantitative RT-PCR and DNA microarray analysis revealed
      unique transcript expression patterns for each of the eight UGTs in Medicago
      organs and cell suspension cultures, and comparison of these patterns with known
      phytochemical profiles suggested in vivo functions for several of the enzymes.

PMID- 17437064
TI  - Regulatory gene candidates and gene expression analysis of cold acclimation in
      winter and spring wheat.
AB  - Freezing tolerance in plants develops through acclimation to cold by growth at
      low, above-freezing temperatures. Wheat is one of the most freezing-tolerant
      plants among major crop species and the wide range of freezing tolerance among
      wheat cultivars makes it an excellent model for investigation of the genetic
      basis of cold tolerance. Large numbers of genes are known to have altered levels
      of expression during the period of cold acclimation and there is keen interest in
      deciphering the signaling and regulatory pathways that control the changes in
      gene expression associated with acquired freezing tolerance. A 5740 feature cDNA
      amplicon microarray that was enriched for signal transduction and regulatory
      genes was constructed to compare changes in gene expression in a highly cold
      tolerant winter wheat cultivar CDC Clair and a less tolerant spring cultivar,
      Quantum. Changes in gene expression over a time course of 14 days detected over
      450 genes that were regulated by cold treatment and were differentially regulated
      between spring and winter cultivars, of these 130 are signaling or regulatory
      gene candidates, including: transcription factors, protein kinases, ubiquitin
      ligases and GTP, RNA and calcium binding proteins. Dynamic changes in transcript
      levels were seen at all periods of cold acclimation in both cultivars. There was
      an initial burst of gene activity detectable during the first day of CA, during
      which 90% of all genes with increases in transcript levels became clearly
      detectable and early expression differential between the two cultivars became
      more disparate with each successive period of cold acclimation.

PMID- 17437065
TI  - Activation of the imprinted Polycomb Group Fie1 gene in maize endosperm requires
      demethylation of the maternal allele.
AB  - Imprinting refers to the epigenetic regulation of gene expression that is
      dependent upon gene inheritance from the maternal or paternal parent. Previously,
      we have identified two maize homologs of the single Arabidopsis Polycomb Group
      gene FIE. Here, we report on the expression pattern of these genes in individual
      gametes before and after fertilization, and on the role of DNA methylation in
      determining the maternal expression of the Fie1 gene. We found that Fie1 is
      neither expressed in the sperm, egg cell nor central cell before fertilization.
      Activation of the Fie1 maternal allele occurs around two days after pollination
      (DAP) in the primary endosperm and peaks at 10-11 DAP coinciding with endosperm
      transition from mitotic division to endoreduplication. In contrast, Fie2 is
      expressed in the egg cell and more intensively in the central cell similar to
      Arabidopsis FIE, which strongly supports the hypothesis that it functions as a
      repressor of endosperm development before fertilization. Using MSRE-PCR and
      bisulfite sequencing, we could show that the methylated inactive state is the
      default status of Fie1 in most tissues. In the endosperm the paternal Fie1 allele
      remains methylated and silent, but the maternal allele appears hypomethylated and
      active, explaining mono-allelic expression of Fie1 in the endosperm. Taking
      together, these data demonstrate that the regulation of Fie1 imprinting in maize
      is different from Arabidopsis and that Fie1 is likely to have acquired important
      novel functions for endosperm development.

PMID- 17437066
TI  - Tissue biocompatibility of new biodegradable drug-eluting stent materials.
AB  - Drug-eluting stents are a recent innovation for endovascular and endourethral
      purposes. The aim of this study was to assess the biocompatibility of new
      biodegradable drug-eluting stent materials in vivo. Rods made of SR-PLDLA (self
      reinforced poly-96L,4D: -lactic acid) covered with P(50L/50D)LA and rods made of
      96L/4D SR-PLA and covered with P(50L/50D)LA including indomethacin 3.3
      microg/mm(2)or dexamethasone 1.5 microg/mm(2), were inserted into the dorsal
      muscles of 20 rabbits serving as test animals. Rods made of silicone and
      organotin-positive polyvinylchloride were used as negative and positive controls.
      The animals were sacrificed after 1 week, 1 month, 2 months or 4 months.
      Histological changes attributable to the operative trauma were seen in all
      specimens at 1 week and 1 month. At 2 months both dexamethasone and indomethacin
      induced less fibrosis than the plain SR-PLDLA covered with P(50L/50D)LA without
      drug. At 4 months dexamethasone induced both chronic inflammatory changes and
      foreign body reaction, whereas the reactions in the indomethacin and drug-free
      plain SR-PLDLA groups were insignificant. The new biodegradable drug-eluting
      stent materials are highly biocompatible. Drug-eluting biodegradable stents may
      offer a promising new treatment modality for vascular and urethral diseases.
      However, further studies are needed to demonstrate their feasibility and
      efficacy.

PMID- 17437067
TI  - Novel fabrication of a polymer scaffold with a dense bioactive ceramic coating
      layer.
AB  - A novel method of coating a polymeric scaffold with a dense ceramic layer was
      developed. This method exploits the fact that only one of the two interlaced 3-D
      channels formed in a ceramic dual-scaffold can be infiltrated with a polymer.
      Firstly, a 3-D graphite network prepared by the rapid prototyping (RP) method was
      dip-coated with hydroxyapatite (HA) slurry, followed by heat-treatment at 1250
      degrees C for 3 h in air. This created an additional 3-D channel through the
      removal of the graphite network, while preserving the pre-existing 3-D channel.
      Thereafter, only one channel was infiltrated with a molten poly(epsilon
      caprolactone) (PCL) polymer at 140 degrees C for 12 h, producing a PCL scaffold
      with a dense, uniform HA coating layer. The sample showed high compressive
      strength with ductile behavior, due to the nature of the PCL polymer, and an
      excellent cellular response afforded by the bioactive HA coating layer. The
      results indicate that this novel technique provides a highly versatile method of
      coating various polymeric scaffolds with bioactive layers in order to endow them
      with advanced functionalities.

PMID- 17437068
TI  - In vitro evaluation of the use of zeolites as biomaterials: effects on simulated
      body fluid and two types of cells.
AB  - Various zeolites were kept in simulated body fluid (SBF) for different periods of
      time. Possible changes that may occur in the crystalline structures of zeolites
      and the chemical composition of SBF were determined by various analysis
      techniques after this treatment. The possible effects of two different zeolites
      on the morphology and viability of chronic myelogeneous leukemia and swiss albino
      fibroblast culture cells were also investigated. It was determined that when
      different types of zeolites were kept in the SBF for up to 14 days, their crystal
      structures were not affected. Observable amounts of Si were detected in the SBF
      samples after their treatment with all the zeolites investigated. Another
      variation in the chemical composition of SBF, worth to mention, was the increase
      of about 10% in its K content after the treatment carried out by using
      clinoptilolite. The zeolites KA and silicalite, which allowed the lowest and
      highest amount of silicon transfer into the SBF, respectively, were observed not
      to have any significant biological effect on the two different cell generations
      investigated under the conditions used in this study.

PMID- 17437069
TI  - Evaluation of polymerization in fluoride-containing composite resins.
AB  - Fluoride-containing restorative materials are frequently utilized to delay or
      inhibit caries. The quality of the fluoride-containing composite resins was
      evaluated by testing their microhardness, polymerization shrinkage, thermal
      expansion coefficient, and surface morphology. Some of them were evaluated in
      conjunction with the thermocycling process. The microhardness values of the
      thermocycled specimens were similar to those of the specimens immersed only in
      distilled water. Among the specimens, Surefil showed the highest (68.6 +/- 1.2
      Hv) value. A linear correlation was found between microhardness and the filler
      content (vol%) of the specimens regardless of their states. Polymerization
      shrinkage rapidly increased during the light curing, and then it reached a
      plateau. The shrinkage values increased as the specimens became thicker. In a
      temperature range of 30 approximately 80 degrees C, the coefficients of thermal
      expansion of the control specimens ranged between 43 x 10(-6)/ degrees C and 77 x
      10(-6)/ degrees C. An inverse correlations were observed between the filler
      content (vol%) and the coefficient of thermal expansion and between microhardness
      and the coefficient of thermal expansion of the control specimens. Tetric Ceram
      showed a perforated or "Swiss-cheese" morphology after thermocycling. It was
      unique and occurred only in this product.

PMID- 17437070
TI  - Factor structure evaluation of the childhood autism rating scale.
AB  - This study investigated the factor structure of the Childhood Autism Rating Scale
      (CARS). Principal components analysis (PCA) and principal axis factor analysis
      (PAF) evaluated archival data from children presenting to a university clinic
      with suspected autism spectrum disorders (ASDs; N = 164). PCA did not replicate
      components identified by DiLalla and Rogers (1994, Domains of the Childhood
      Autism Rating Scale: Relevance for diagnosis and treatment. Journal of Autism and
      Developmental Disorders, 24(2), 115-128) and Stella, Mundy, and Tuchman (1999,
      Social and nonsocial factors in the Childhood Autism Rating Scale. Journal of
      Autism and Developmental Disorders, 29(4), 307-317). PAF identified correlated
      Social-Communication, Social Interaction, Stereotypies and Sensory Abnormalities,
      and Emotional Regulation factors. Results differed across studies; however, each
      identified ASD related constructs conceptually consistent with DSM-IV. Although
      its development predates the DSM-IV, and many newer measures are available, the
      CARS' psychometric properties, conceptual relevance, and flexible administration
      procedures support its continued use as a screening device in the diagnostic
      decision-making process.

PMID- 17437071
TI  - [Perioperative patient management. Evaluation of subjective stress and demands of
      patients undergoing elective gynaecological surgery].
AB  - BACKGROUND: The aim of this investigation was to assess the extent of stress and
      demands in patients during preparation for general anesthesia for elective
      surgical procedures. PATIENTS AND METHODS: A total of 52 female patients
      scheduled for elective gynecological surgery under general anesthesia were
      included in this prospective study. The extent and time course of actual demands
      describing perceived emotional stress was assessed at close intervals using the
      German version of the Questionnaire for Actual Demands (KAB). Pre-operative and
      postoperative anxiety was assessed using part one of Spielberger's state-trait
      anxiety inventory (STAI-X1). This was compared to hemodynamic (heart rate und
      blood pressure) and endocrinal stress parameters [cortisol concentration in serum
      and saliva, prolactin and dehydroepiandrosteronesulfate (DHEA-S) in serum].
      Postoperatively, all patients were asked to rate the quality of care during
      preparation for general anesthesia. RESULTS: The extent of patients' demands and
      stress during preparation for general anesthesia could be quantified by the short
      questionnaire for the actual demands (KAB). So-called objective stress parameters
      like hemodynamic and endocrinal data alone did not correlate with perceived
      stress. However, the subjective information correlated with the nature of the
      underlying diagnosis. The postoperative assessment of quality of care during
      preparation for general anesthesia did not correlate with the course of actual
      demands and stress. CONCLUSION: In future studies assessing the perioperative
      management of patients and quality of care, standardized testing questionnaires
      should be preferred, instead of vegetative parameters alone, to reliably evaluate
      perioperative demands and stress in surgical patients.

PMID- 17437072
TI  - [Strategies for quality assessment of emergency helicopter rescue systems. The
      Graz model].
AB  - PURPOSE: Preclinical emergency medical treatment necessitates a comprehensive
      interdisciplinary knowledge by the emergency physician as well as a high level of
      manual dexterity. The quality of treatment therefore depends on the level of
      education and continuous training in emergency medical techniques. Based on an
      evaluation of the frequency of life-saving interventions by a physician-staffed
      rescue helicopter system, strategies for in-hospital training of relevant skills
      are suggested. MATERIAL AND METHODS: At the outset, 10 important areas of
      treatment (e.g. intubation, chest tube etc.) and their frequency in emergency
      medical services were defined as the standard to be attained by emergency
      physicians within 1 year. The selection of the areas of treatment was based to
      some extent on international recommendations. The actual frequencies of the
      prehospital interventions were compared to the required minimum numbers by
      retrospective analysis of the helicopter rescue database (NACA-X). RESULTS:
      During the observation period of 1 year, 20 emergency physicians responded to 956
      prehospital emergency calls. A life-threatening condition requiring an on-site
      intervention occurred in only 521 (54.5%) patients, so that the majority of
      physicians did not perform the required minimum number of interventions. In order
      to maintain their level of skill, the emergency physicians were required to
      undertake additional training at the local university hospital. CONCLUSION: The
      frequency of on-site life-saving interventions in emergency medicine is
      insufficient to fulfill the quota necessary to maintain adequate training of
      emergency physicians. Only a link-up program at a hospital for primary care can
      ensure an adequate training level.

PMID- 17437074
TI  - A key player in biomedical sciences and clinical service in China, Chinese
      Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC).
AB  - The Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College
      (PUMC) is the largest medical institution in China and has a leading high-level
      multidisciplinary medical research and medial service. Under the CAMS and PUMC
      infrastructure, there are 17 biomedical institutes and 6 large hospitals, which
      cover most fields of the human disease-related research. CAMS and PUMC has always
      attached great emphasis on the control and cure of severe diseases, as well as a
      series of innovative drug researches, and has made significant progress in those
      fields. The long-term goals for CAMS and PUMC in the future development are:
      reaching the international advanced level in the areas of severe disease
      prediction, prevention, control, diagnosis, and research on drug innovation;
      establishing theoretical and technological system for explanation of the
      mechanism of severe diseases, which possesses Chinese style and represents the
      frontier level in the world, and at the same time, providing scientific support
      for the prevention and treatment of severe disease and making contribution to the
      establishment and development of a harmonious society in China.

PMID- 17437073
TI  - The promise of TRAIL--potential and risks of a novel anticancer therapy.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising
      new anticancer biotherapeutic. As shown by many preclinical studies, TRAIL
      efficiently induces apoptosis in numerous tumor cell lines but not in the
      majority of normal cells. However, an increasing number of publications report on
      a predominance of TRAIL resistance in primary human tumor cells, which require
      sensitization for TRAIL-induced apoptosis. Sensitization of cancer cells by
      treatment with chemotherapeutic drugs and irradiation has been shown to restore
      TRAIL sensitivity in many TRAIL-resistant tumor cells. Accordingly TRAIL
      treatment has been successfully used in different in vivo models for the
      treatment of tumors also in combination with chemotherapeutics without
      significant toxicity. However, some reports demonstrated toxicity of TRAIL alone
      or in combination with chemotherapeutic drugs in normal cells. This review
      summarizes data concerning the apoptosis-inducing pathways and efficacy of TRAIL,
      alone or in combination with chemotherapeutic drugs, in primary cancer cells
      compared to the unwanted effects of TRAIL treatment on normal tissue. We discuss
      the different in vitro tumor cell models and the potential of different
      recombinant forms of TRAIL or agonistic antibodies to TRAIL death receptors. Most
      preclinical studies show a high efficiency of a combinatorial TRAIL-based therapy
      in animal models and in primary human ex vivo tumor cells with a low toxicity in
      normal cells. Accordingly clinical phase I/II studies have begun and will be
      developed further with caution.

PMID- 17437075
TI  - [Efficacy of multikinase inhibitors in the treatment of advanced renal cell
      cancer. A snapshot].
AB  - Due to the chemoresistance of renal cell cancer, cytokine-based therapeutic
      approaches were considered the standard treatment for patients with metastatic
      disease. At present, data that are available from a few phase II/III studies,
      dealing both with the first- and second-line treatment of patients suffering from
      systemic progression of RCC, indicate the significantly higher clinical efficacy
      of multikinase inhibitors when compared with cytokine-based therapeutic regimens.
      In this context, sorafenib (Nexavar, BAY 43-9006) and sunitinib (Sutent, SU
      011248) are the most frequently applied and most intensively investigated
      substances. In Germany, with regard to a phase III study reported at the ASCO
      congress in 2006, sunitinib received approval for the first-line therapy of
      metastatic RCC. The application of multikinase inhibitors follows the principle
      of targeting such mediators that are considered to be substantially involved in
      the pathogenesis and particularly progression of renal cell cancer within
      relatively well-defined molecular pathways. The aim of the present paper is to
      address and to critically discuss the clinical data that are currently available
      regarding the therapeutic efficacy of kinase inhibitors during the treatment of
      metastatic RCC.

PMID- 17437076
TI  - Biliary cystic intraductal papillary mucinous tumor and
      cystadenoma/cystadenocarcinoma: differentiation by CT.
AB  - PURPOSE: To identify differential findings of biliary cystic intraductal
      papillary mucinous tumor (IPMT) and biliary cystadenoma/cystadenocarcinoma on CT
      images. MATERIALS AND METHODS: Records of 7 patients with biliary cystic IPMT and
      17 patients with biliary cystadenoma/cystadenocarcinoma were accessed. A
      pathologist reviewed gross morphologic and microscopic findings and confirmed the
      diagnosis. Two radiologists who were blind to the pathologic diagnosis reviewed
      CT images regarding size of cystic mass, mural nodule, septa, calcification,
      dilatation of the proximal, and distal bile ducts to the tumor, and the results
      were analyzed using multivariate analysis. RESULTS: Mural nodule and dilatation
      of the bile ducts distal to the cystic tumor were more commonly seen in patients
      with cystic IPMT than in patients with biliary cystadenoma/cystadenocarcinoma and
      these are statistically significant, the P values being 0.029 and 0.016,
      respectively. Size of the cystic tumor, presence of septa, calcification, and
      dilatation of the bile duct proximal to the cystic tumor were not statistically
      different. CONCLUSION: Biliary cystic IPMT could be differentiated from biliary
      cystadenoma/cystadenocarcinoma on CT images based on the presence of mural
      nodules and dilatation of the bile ducts distal to the cystic tumor.

PMID- 17437077
TI  - Can we out-run the diabetes epidemic?

PMID- 17437078
TI  - Comment on: Nathan DM, Buse JB, Davidson MB et al (2006) Management of
      hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and
      adjustment of therapy. A consensus statement from the American Diabetes
      Association and the European Association for the Study of Diabetes. Diabetologia
      49:1711-1721.

PMID- 17437079
TI  - Development of diabetes in obese, insulin-resistant mice: essential role of
      dietary carbohydrate in beta cell destruction.
AB  - AIMS/HYPOTHESIS: The role of dietary carbohydrate in the pathogenesis of type 2
      diabetes is still a subject of controversial debate. Here we analysed the effects
      of diets with and without carbohydrate on obesity, insulin resistance and
      development of beta cell failure in the obese, diabetes-prone New Zealand Obese
      (NZO) mouse. MATERIALS AND METHODS: NZO mice were kept on a standard diet (4%
      [w/w] fat, 51% carbohydrate, 19% protein), a high-fat diet (15, 47 and 17%,
      respectively) and a carbohydrate-free diet in which carbohydrate was exchanged
      for fat (68 and 20%, respectively). Body composition and blood glucose were
      measured over a period of 22 weeks. Glucose tolerance tests and euglycaemic
      hyperinsulinaemic clamps were performed to analyse insulin sensitivity. Islet
      morphology was assessed by immunohistochemistry. RESULTS: Mice on carbohydrate
      containing standard or high-fat diets developed severe diabetes (blood glucose
      >16.6 mmol/l, glucosuria) due to selective destruction of pancreatic beta cells
      associated with severe loss of immunoreactivity of insulin, glucose transporter 2
      (GLUT2) and musculoaponeurotic fibrosarcoma oncogene homologue A (MafA). In
      contrast, mice on the carbohydrate-free diet remained normoglycaemic and
      exhibited hyperplastic islets in spite of a morbid obesity associated with severe
      insulin resistance and a massive accumulation of macrophages in adipose tissue.
      CONCLUSIONS/INTERPRETATION: These data indicate that the combination of obesity,
      insulin resistance and the inflammatory response of adipose tissue are
      insufficient to cause beta cell destruction in the absence of dietary
      carbohydrate.

PMID- 17437080
TI  - Variants of transcription factor 7-like 2 (TCF7L2) gene predict conversion to
      type 2 diabetes in the Finnish Diabetes Prevention Study and are associated with
      impaired glucose regulation and impaired insulin secretion.
AB  - AIMS/HYPOTHESIS: We investigated the association of variants of the transcription
      factor 7-like 2 (TCF7L2) gene with: (1) incident diabetes in the Finnish Diabetes
      Prevention Study (DPS, Study I); (2) type 2 diabetes and impaired glucose
      regulation (i.e. IGT or IFG) in a cross-sectional study (Study II); and (3)
      insulin secretion, insulin sensitivity and adipose tissue expression of TCF7L2 in
      offspring of type 2 diabetic probands (III). SUBJECTS AND METHODS: Study I (the
      DPS) included 507 individuals with IGT who were randomly allocated to control and
      intervention groups and followed for an average of 3.9 years to monitor for
      progression to diabetes. Study II was a population-based cross-sectional study of
      1,766 men, aged 50-70 years, randomly selected from the population of Kuopio,
      eastern Finland. Study III included 238 non-diabetic offspring of patients with
      type 2 diabetes. Genotyping of rs12255372 and rs7903146 of TCF7L2 was carried
      out. RESULTS: In the DPS, the TT genotype of rs12255372 was significantly
      associated with an adjusted 2.85-fold risk (95% CI 1.17-6.95, p = 0.021) of
      incident diabetes in the control group, but not in the intervention group. In
      Study II, the adjusted odds ratio in subjects with the TT genotype was 3.40 (1.45
      7.97, p = 0.005) for the comparison of diabetic subjects with normoglycaemic
      subjects. The T allele of rs12255372 was significantly associated with decreased
      insulin secretion (Studies II, III). Expression of TCF7L2 in adipose tissue
      tended to be lower in subjects with the TT risk genotypes of rs12255372 and
      rs7903146. CONCLUSIONS/INTERPRETATION: The variant of rs12255372 of TCF7L2 was
      associated with incident type 2 diabetes in the DPS and in a separate population
      based cross-sectional study. Impaired insulin secretion is likely to be the main
      cause for our findings.

PMID- 17437081
TI  - Human high-density lipoprotein particles prevent activation of the JNK pathway
      induced by human oxidised low-density lipoprotein particles in pancreatic beta
      cells.
AB  - AIMS/HYPOTHESIS: We explored the potential adverse effects of pro-atherogenic
      oxidised LDL-cholesterol particles on beta cell function. MATERIALS AND METHODS:
      Isolated human and rat islets and different insulin-secreting cell lines were
      incubated with human oxidised LDL with or without HDL particles. The insulin
      level was monitored by ELISA, real-time PCR and a rat insulin promoter construct
      linked to luciferase gene reporter. Cell apoptosis was determined by scoring
      cells displaying pycnotic nuclei. RESULTS: Prolonged incubation with human
      oxidised LDL particles led to a reduction in preproinsulin expression levels,
      whereas the insulin level was preserved in the presence of native LDL
      cholesterol. The loss of insulin production occurred at the transcriptional
      levels and was associated with an increase in activator protein-1 transcriptional
      activity. The rise in activator protein-1 activity resulted from activation of c
      Jun N-terminal kinases (JNK, now known as mitogen-activated protein kinase 8
      [MAPK8]) due to a subsequent decrease in islet-brain 1 (IB1; now known as MAPK8
      interacting protein 1) levels. Consistent with the pro-apoptotic role of the JNK
      pathway, oxidised LDL also induced a twofold increase in the rate of beta cell
      apoptosis. Treatment of the cells with JNK inhibitor peptides or HDL countered
      the effects mediated by oxidised LDL. CONCLUSIONS/INTERPRETATION: These data
      provide strong evidence that oxidised LDL particles exert deleterious effects in
      the progression of beta cell failure in diabetes and that these effects can be
      countered by HDL particles.

PMID- 17437082
TI  - The anterior-posterior laxity after total knee arthroplasty inserted with a
      ligament tensor.
AB  - Goal of this study is to determine the anterior-posterior laxity in 30 degrees of
      knee flexion for a posterior cruciate retaining total knee arthroplasty with a
      relative dished insert and implanted with a ligament tensor. Furthermore, the
      correlation between these AP laxities and the postoperative range of motion (ROM)
      and postoperative Knee Society Score (KSS) is analysed. Fifty-one balanSys total
      knee arthroplasties were performed in 49 patients between 1998 and 2000. These
      arthroplasties are analysed with respect to AP laxity (Rolimeter), ROM and KSS
      with a mean follow-up of 4.6 years. The mean anterior laxity is 2.8 mm with no
      posterior laxities at all. The average postoperative ROM is 110 degrees with an
      average KSS of 142. No correlations between AP-laxity and postoperative ROM or
      between AP-laxity and postoperative KSS are found. A posterior cruciate retaining
      TKA with a relative dished insert and implanted with a tensor is very stable in
      the anterior-posterior direction in 30 degrees of knee flexion. This limited
      laxity does not seem to disadvantage the mean postoperative ROM and KSS, when
      compared to other TKA studies.

PMID- 17437084
TI  - Posterior double PCL sign: a case report of unusual MRI finding of bucket-handle
      tear of medial meniscus.
AB  - Among the MRI signs of bucket-handle tears of medial meniscus, double posterior
      cruciate ligament (PCL) sign denotes a low signal band anterior and parallel to
      the PCL, which looks like another PCL in MR images. If the bucket-handle fragment
      subsequently tears at the anterior horn, the torn meniscal substance can be
      displaced to the posterosuperior region of the PCL, and looks like another PCL
      behind the original PCL. We propose the lesion be called the "posterior double
      PCL sign" in contrast to the ordinary double PCL sign. We present a case showing
      the posterior double PCL sign.

PMID- 17437083
TI  - A meta-analysis of stability of autografts compared to allografts after anterior
      cruciate ligament reconstruction.
AB  - Allografts have recently become increasingly popular for anterior cruciate
      ligament reconstruction (ACLR) in the United States even though many studies have
      shown high allograft failure rates (Gorschewsky et al. in Am J Sports Med
      33:1202, 2005; Pritchard et al. in Am J Sports Med 23:593, 2005; Roberts et al.
      in Am J Sports Med 19:35, 2006) and no meta-analysis or systematic review of
      allograft clinical stability rates in comparison to autog rafts has previously
      been performed. We hypothesized that allografts would demonstrate overall lower
      objective stability rates compared to autografts. To test this hypothesis we
      performed a meta-analysis of autograft and allograft stability data. A pubmed
      literature search of all allograft series in humans published in English was
      performed. Articles were then bibliographically cross-referenced to identify
      additional studies. Series inclusion criteria were arthrometric follow-up data
      using at least 30 lb or maximum manual force, stratified presentation of
      stability data and minimum two-year follow-up. Twenty allograft series were thus
      selected and compared to a previously published data set of all BPTB and
      Hamstring (HS) autograft ACLR series using the same study inclusion criteria and
      analytic and statistical methodology. IKDC standards of 0-2 mm (normal) and >5 mm
      (abnormal) side-to-side differences were adopted to compare studies. Normal
      stability for all autografts was 72 versus 59% for all allografts (P < 0.01).
      Abnormal stability was 5% for all autografts versus 14% for all allografts (P <
      0.01). Bone-patellar-tendon-bone (BPTB) autograft normal stability was 66% versus
      57% for BPTB allografts (P < 0.01). Abnormal BPTB autograft stability was 6
      versus 16% for BPTB allograft. Hamstring autograft normal or abnormal stability
      rates were 77% and 4% and were compared to soft tissue allografts as a group
      which were 64% and 12% (P < 0.01). This is the first meta-analysis comparing
      autograft to allograft stability in ACLR. Allografts had significantly lower
      normal stability rates than autografts. The allograft abnormal stability rate,
      which usually represents graft failure, was significantly higher than that of
      autografts: nearly three times greater. It would therefore appear that autografts
      are the graft of choice for routine ACLR with allografts better reserved for
      multiple ligament-injured knees where extra tissue may be required.

PMID- 17437085
TI  - Evaluation of BioCorkscrew and Bioknotless RC suture anchor rotator cuff repair
      fixation: an in vitro biomechanical study.
AB  - This in vitro biomechanical study used cadaveric specimens to compare the rotator
      cuff repair fixation provided by BioCorkscrew and Bioknotless RC suture anchors.
      Three cm wide by 1-cm long full-thickness supraspinatus defects were repaired
      using either two BioCorkscrew suture anchors with combined vertical and
      horizontal mattress sutures (n = 7) or three Bioknotless RC suture anchors with
      simple sutures (n = 7). Therefore, the BioCorkscrew suture anchor group had two
      sutures per anchor (four total sutures), while the Bioknotless RC suture anchor
      group had one suture per anchor (three total sutures). Two-phase cyclic (5-100 N,
      1,000 cycles and 5-180 N, 2,000 cycles) and load to failure tests (31 mm/s) were
      performed. Non-parametric statistics were used to compare group differences (P <
      0.05). All of the BioCorkscrew group specimens (seven of seven) completed the two
      phase cyclic test regimen without failure or gapping >/= 5 mm, compared to only
      three of seven of the Bioknotless RC group (Fisher's Exact test = 0.03). Groups
      did not differ for repair site gapping during the 5-100 N cyclic test phase
      (Fisher's Exact test = 0.77), however more of the Bioknotless RC group displayed
      gapping >/= 5 mm during the 5-180 N cyclic test phase than the BioCorkscrew group
      (P = 0.02). The BioCorkscrew group also displayed greater yield load during load
      to failure testing (492.2 +/- 204 N vs. 296.4 +/- 155 N, P = 0.03). In this in
      vitro biomechanical study, the BioCorkscrew group with combined vertical and
      horizontal mattress sutures displayed greater cyclic test survival, less repair
      site gapping, and superior yield load compared to the Bioknotless RC group with
      simple sutures. These results in human cadaveric rotator cuff-humerus specimens
      suggest better immediate post-operative repair site strength and a reduced need
      for post-operative restrictions. Clinical studies are needed to determine how
      these rotator cuff repair modes withstand the forces of early rehabilitation and
      activities of daily living that potentially influence patient outcomes.

PMID- 17437086
TI  - Characteristics of cell-mediated, anti-listerial immunity induced by a naturally
      avirulent Listeria monocytogenes serotype 4a strain HCC23.
AB  - The characteristics of cell-mediated, anti-listerial immune response initiated by
      an avirulent Listeria monocytogenes serotype 4a strain HCC23 was assessed.
      Similar to virulent strain EGD, avirulent strain HCC23 grew readily within
      macrophage-like J774 cells, but nonhemolytic strain ATCC 15313 did not. Compared
      with EGD, HCC23 induced a relatively low level of gamma interferon (IFN-gamma) in
      mice, and ATCC 15313 stimulated no detectable IFN-gamma. The percentages of gated
      CD4 T cells from mice immunized with EGD and HCC23 showed a notable drop (to 30%)
      at 21 days post exposure in comparison with that (about 50%) from ATCC 15313
      injected or untreated mice; and the percentage of gated NK cells from EGD
      immunized group was markedly higher than those from other treatment groups. Mice
      immunized with HCC23 and EGD developed an equally strong protective immunity
      against listeriosis that was effective in both short and long terms, but those
      injected with ATCC 15313 or saline succumbed to listeriosis within 6 days of
      challenge.

PMID- 17437088
TI  - Eberhard Denk wins ABC Best Paper Award.

PMID- 17437087
TI  - Stress-induced relapse to cocaine seeking: roles for the CRF(2) receptor and CRF
      binding protein in the ventral tegmental area of the rat.
AB  - RATIONALE: Footshock reinstates cocaine seeking in cocaine-experienced rats by
      inducing corticotropin-releasing factor (CRF) and glutamate release in the
      ventral tegmental area (VTA) and thus activating VTA dopaminergic neurons.
      Footshock-induced VTA glutamate release, dopamine activation and reinstatements
      are blocked by VTA administration of a alpha-helical CRF, a nonselective CRF
      receptor antagonist. The effects of selective CRF antagonists have not yet been
      reported. OBJECTIVE: The present studies were designed to explore the roles of
      VTA CRF receptor subtypes and CRF-BP in these effects induced by footshock.
      METHODS: Rats were first trained to lever-press for intravenous cocaine (1
      mg/infusion/0.13 ml, FR-1 schedule), and then tested under extinction conditions
      until response rates returned to the pretraining baseline. Reinstatements, VTA
      glutamate and dopamine levels [microdialysis with high performance liquid
      chromatography (HPLC)] were then assessed, under various pharmacological
      conditions, after mild inescapable footshock. RESULTS: Footshock-induced
      reinstatement of cocaine seeking and release of VTA glutamate and dopamine were
      blocked by selective blockade of VTA CRF(2) receptors (CRF(2)Rs) but not
      CRF(1)Rs. VTA perfusion of CRF or CRF(2)R agonists that have strong affinity for
      CRF-BP mimicked the effects induced by footshock while CRFR agonists that do not
      bind CRF-BP were ineffective. CRF(6-33), which competes for the CRF binding site
      on CRF-BP, attenuated the effects of CRF or urocortin I on VTA glutamate and
      dopamine release and on reinstatement of cocaine seeking. CONCLUSIONS: The
      present studies revealed a role of VTA CRF-BP and suggest an involvement of
      CRF(2)R in the effectiveness of stress in triggering glutamate and dopamine
      release and cocaine seeking in drug-experienced animals.

PMID- 17437089
TI  - Analysis of cysteine-containing proteins using precolumn derivatization with N-(2
      ferroceneethyl)maleimide and liquid chromatography/electrochemistry/mass
      spectrometry.
AB  - N-(2-ferroceneethyl)maleimide (FEM) is introduced as an electroactive
      derivatizing agent for thiol functionalities in proteins. Using appropriate
      reaction conditions, the derivatization is completed within five minutes and no
      unspecific labeling of free amino functions is observed. Liquid
      chromatography/electrochemistry/mass spectrometry was used to detect the reaction
      products. The reagent is a useful tool for determining the number of free thiol
      groups or the total number of free and disulfide-bound thiol groups in proteins.
      The electrochemical cell provides additional information, because the increase in
      mass spectrometric response upon electrochemical oxidation of the neutral
      ferrocene to the charged ferrocinium groups is monitored. The method was
      successfully applied to the analysis of native proteins and their tryptic
      digests.

PMID- 17437090
TI  - A comparison of three solvent-free techniques coupled with gas chromatography for
      determining trihalomethanes in urine samples.
AB  - The analysis of volatile organic compounds in samples of biological fluids
      characterized by complex matrices is highly challenging. This paper presents a
      comparison of the results obtained in this field using three solvent-free
      techniques: thin-layer headspace with autogenous generation of liquid sorbent
      (TLHS) and membrane separation of the trace substances (pervaporation, PV), both
      of which are coupled to direct aqueous injection gas chromatography-electron
      capture detection (TLHS-DAI-GC-ECD and PV-DAI-GC-ECD), as well as conventional
      static headspace analysis followed by GC analysis with ECD detection (HS-GC-ECD).
      Basic validation parameters of the HS-GC-ECD, TLHS-DAI-GC-ECD and PV-DAI-GC-ECD
      procedures were calculated for water and urine samples. The calibration curves
      for all procedures were linear within the concentration range examined. The
      intermediate precisions of the procedures were good and reached about 10% (for
      all analytes) for HS-GC-ECD and TLHS-DAI-GC-ECD. The poorest results were
      obtained for PV-DAI-GC-ECD: about 20% for all analytes. The lowest method
      detection limits were obtained for the TLHS-DAI-GC-ECD procedure: below 0.0022
      microg/L for all analytes. The enrichment factors did not differ significantly
      between water and urine samples, indicating little or no matrix effect in all
      procedures.

PMID- 17437091
TI  - Multitechnique mass-spectrometric approach for the detection of bovine
      glutathione peroxidase selenoprotein: focus on the selenopeptide.
AB  - Glutathione peroxidase (isolated from bovine erythrocytes) and its behaviour
      during alkylation and enzymatic digestion were studied by various hyphenated
      techniques: gel electrophoresis-laser ablation (LA) inductively coupled plasma
      (ICP) mass spectrometry (MS), size-exclusion liquid chromatography-ICP MS,
      capillary high-performance liquid chromatography (capHPLC)-ICP MS, matrix
      assisted laser desorption/ionization (MALDI) time-of-flight (TOF) MS,
      electrospray MS, and nanoHPLC-electrospray ionization (ESI) MS/MS. ESI TOF MS and
      MALDI TOF MS allowed the determination of the molecular mass but could not
      confirm the presence of selenium in the protein. The purity of the protein with
      respect to selenium species could be evaluated by LA ICP MS and size-exclusion
      chromatography (SEC)-ICP MS under denaturating and nondenaturating conditions,
      respectively. SEC-ICP MS and capHPLC-ICP MS turned out to be valuable techniques
      to study the enzymolysis efficiency, miscleavage and artefact formation during
      derivatization and tryptic digestion. For the first time the parallel ICP MS and
      ESI MS/MS data are reported for the selenocysteine-containing peptide extracted
      from the gel; capHPLC-ICP MS allowed the sensitive detection of the selenopeptide
      regardless of the matrix and nanoHPLC-electrospray made possible its
      identification.

PMID- 17437092
TI  - Real-time PCR detection of telomerase activity using specific molecular beacon
      probes.
AB  - Telomerase is a potentially important biomarker and a prognostic indicator of
      cancer. Several techniques for assessing telomerase activity, including the
      telomeric repeat amplification protocol (TRAP) and its modified versions, have
      been developed. Of these methods, real-time quantitative TRAP (RTQ-TRAP) is
      considered the most promising. In this work, a novel RTQ-TRAP method is developed
      in which a telomeric repeats-specific molecular beacon is used. The use of the
      molecular beacon can improve the specificity of the RTQ-TRAP assay, making the
      method suitable for studying the overall processivity results and the turnover
      rate of telomerase. In addition, the real-time, closed-tube protocol used
      obviates the need for post-amplification procedures, reduces the risk of
      carryover contamination, and supports high throughput. Its performance in
      synthetic telomerase products and cell extracts suggests that the developed
      molecular beacon assay can further enhance the clinical utility of telomerase
      activity as a biomarker/indicator in cancer diagnosis and prognosis. The method
      also provides a novel approach to the specific detection of some particular gene
      sequences to which sequence-specific fluorogenic probes cannot be applied
      directly. Figure Real-time PCR detection of telomerase activity using specific
      molecular beacon probes.

PMID- 17437093
TI  - Explicit contextual information selectively contributes to predictive switching
      of internal models.
AB  - Many evidences suggest that the central nervous system (CNS) acquires and
      switches internal models for adaptive control in various environments. However,
      little is known about the neural mechanisms responsible for the switching. A
      recent computational model for simultaneous learning and switching of internal
      models proposes two separate switching mechanisms: a predictive mechanism purely
      based on contextual information and a postdictive mechanism based on the
      difference between actual and predicted sensorimotor feedbacks. This model can
      switch internal models solely based on contextual information in a predictive
      fashion immediately after alteration of the environment. Here we show that when
      subjects simultaneously adapted to alternating blocks of opposing visuomotor
      rotations, explicit contextual information about the rotations improved the
      initial performance at block alternations and asymptotic levels of performance
      within each block but not readaptation speeds. Our simulations using separate
      switching mechanisms duplicated these effects of contextual information on
      subject performance and suggest that improvement of initial performance was
      caused by improved accuracy of the predictive switch while adaptation speed
      corresponds to a switch dependent on sensorimotor feedback. Simulations also
      suggested that a slow change in output signals from the switching mechanisms
      causes contamination of motor commands from an internal model used in the
      previous context (anterograde interference) and partial destruction of internal
      models (retrograde interference). Explicit contextual information prevents
      destruction and assists memory retention by improving the changes in output
      signals. Thus, the asymptotic levels of performance improved.

PMID- 17437094
TI  - Pilomatricomas in children: imaging characteristics with pathologic correlation.
AB  - BACKGROUND: Although pilomatricoma commonly occurs in children, there is still a
      poor understanding of the imaging characteristics of pilomatricoma and lack of
      agreement regarding its imaging findings and histopathologic features.
      OBJECTIVES: To characterize the radiologic appearance of pilomatricomas on US,
      CT, and MR and to correlate the imaging findings with histopathologic features.
      MATERIALS AND METHODS: The imaging findings of 47 pilomatricomas on US (n = 17),
      CT (n = 31), and MR (n = 5) were retrospectively evaluated. Pathologic specimens
      of all cases were reviewed and compared with imaging findings. RESULTS: All
      lesions were well-circumscribed, subcutaneous nodules with partial attachment to
      the overlying skin. On US, the lesions were mostly hyperechoic with posterior
      acoustic shadowing and hypoechoic rim. On CT, they appeared as enhancing soft
      tissue masses with varying amounts of calcification. MR findings were internal
      reticulations and patchy areas on T2-weighted images and contrast-enhanced T1
      weighted images, corresponding to edematous stroma on pathology. Peritumoral
      inflammatory changes and connective capsule on pathology were well correlated
      with imaging findings. CONCLUSION: Pilomatricoma should be considered when US or
      CT shows a well-defined hyperechoic or calcific nodule in subcutaneous fat
      attached to the skin in children. MR images may be helpful in diagnosis.
      Pathologic findings are well correlated with imaging findings.

PMID- 17437095
TI  - Benefit of fluoroscopically guided intraarticular, long-acting corticosteroid
      injection for subtalar arthritis in juvenile idiopathic arthritis.
AB  - BACKGROUND: Children with arthritis may endure a lifetime of disfigurement,
      dysfunction, and pain if acute inflammation progresses to chronic changes in the
      joint cartilage and underlying bone. Intraarticular steroids have become an
      integral component of treatment, but at times are difficult to deliver to joints,
      such as the subtalar joint, that have complex anatomies. OBJECTIVE: We describe
      our technique and outcomes using fluoroscopically guided intraarticular subtalar
      steroid injection in patients with active symptoms of juvenile idiopathic
      arthritis (JIA). MATERIALS AND METHODS: Fluoroscopically guided subtalar joint
      injections were performed in 38 children (mean age 6.7 years). Medical records
      were reviewed retrospectively and improvement was evaluated clinically by the
      degree of foot movement in eversion and inversion. RESULTS: Subtalar joint
      injection was technically successful in 100% of the JIA patients with improvement
      in physical symptoms in 34/38 (89%). Of the 38 children, 32 were followed up
      within 13 weeks of the initial injection and, therefore, satisfied the
      eligibility criteria for resolution of arthritis. Of these 32 children, 14 showed
      clinical resolution (44%). The mean duration of improvement was 1.2 +/- 0.9
      years. Children with a longer interval (>1 year) from diagnosis to treatment had
      significantly less resolution (P = 0.04). Local subcutaneous atrophy or
      hypopigmentation were observed in 53% of the children after steroid injection
      (20/38). These minor complications were associated with a greater volume of
      steroid injected into the site per child (P = 0.02). CONCLUSION: Fluoroscopically
      guided subtalar joint injection is an effective treatment for subtalar
      arthropathy. Prompt referral for intraarticular steroid treatment in the acute
      phase improves response. Skin changes often occur at the injection site, and
      specific precautions should be employed to reduce this risk. Prospective study is
      indicated to determine the most effective treatment strategy to prevent long-term
      pain and disability.

PMID- 17437096
TI  - Pediatric gastrointestinal vascular anomalies: imaging and therapeutic issues.
AB  - Vascular anomalies are an uncommon cause of gastrointestinal bleeding. Imaging
      plays an important role in the diagnosis and therapy of these anomalies. Accurate
      diagnosis, classification and awareness of associated syndromes are mandatory for
      applying the appropriate management. In this pictorial essay we review the
      classification, imaging characteristics and treatment of gastrointestinal
      vascular anomalies.

PMID- 17437097
TI  - Construction of an S-layer protein exhibiting modified self-assembling properties
      and enhanced metal binding capacities.
AB  - The functional S-layer protein gene slfB of the uranium mining waste pile isolate
      Bacillus sphaericus JG-A12 was cloned as a polymerase chain reaction product into
      the expression vector pET Lic/Ek 30 and heterologously expressed in Escherichia
      coli Bl21(DE3). The addition of His tags to the N and C termini enabled the
      purification of the recombinant protein by Ni-chelating chromatography. The Ni
      binding capacity of the His-tagged recombinant S-layer protein was compared with
      that of the wild-type S layer. The inductively coupled plasma mass spectrometry
      analyses demonstrate a significantly enhanced Ni binding capability of the
      recombinant protein. In addition, the self-assembling properties of the purified
      modified S-layer proteins were studied by light microscopy and scanning electron
      microscopy. Whereas the wild-type S-layer proteins re-assembled into regular
      cylindric structures, the recombinant S-layer proteins reassembled into regular
      sheets that formed globular agglomerating structures. The nanoporous structure of
      the protein meshwork, together with its enhanced Ni binding capacity, makes the
      recombinant S-layer attractive as a novel self-assembling biological template for
      the fabrication of metal nanoclusters and construction of nanomaterials that are
      of technical interest.

PMID- 17437098
TI  - Glutamate production by Corynebacterium glutamicum: dependence on the
      oxoglutarate dehydrogenase inhibitor protein OdhI and protein kinase PknG.
AB  - We recently showed that the activity of the 2-oxoglutarate dehydrogenase complex
      (ODHC) in Corynebacterium glutamicum is controlled by a novel regulatory
      mechanism that involves a 15-kDa protein called OdhI and serine/threonine protein
      kinase G (PknG). In its unphosphorylated state, OdhI binds to the E1 subunit
      (OdhA) of ODHC and, thereby, inhibits its activity. Inhibition is relieved by
      phosphorylation of OdhI at threonine-14 by PknG under conditions requiring high
      ODHC activity. In this work, evidence is provided that the dephosphorylation of
      phosphorylated OdhI is catalyzed by a phospho-Ser/Thr protein phosphatase encoded
      by the gene cg0062, designated ppp. As a decreased ODHC activity is important for
      glutamate synthesis, we investigated the role of OdhI and PknG for glutamate
      production under biotin limitation and after addition of Tween-40, penicillin, or
      ethambutol. A DeltaodhI mutant formed only 1-13% of the glutamate synthesized by
      the wild type. Thus, OdhI is essential for efficient glutamate production. The
      effect of a pknG deletion on glutamate synthesis was dependent on the induction
      conditions. Under strong biotin limitation and in the presence of ethambutol, the
      DeltapknG mutant showed significantly increased glutamate production, offering a
      new way to improve production strains.

PMID- 17437100
TI  - Giant cell tumor complicating Paget disease of long bone.
AB  - Giant cell tumor (GCT) is a rare complication of Paget disease of bone. It
      usually occurs in the skull or pelvic bones of patients with long-standing
      polyostotic disease. This report describes a 62-year-old patient who presented
      with monostotic Paget disease of the distal femur complicated by GCT. He had a 2
      year history of discomfort and pain in his left knee. Conventional plain films
      and MRI demonstrated the characteristic bone changes of Paget disease and an
      associated lytic lesion involving the epiphyseal and metaphyseal regions of the
      distal femur. A diagnostic curettage showed the characteristic histopathologic
      features of Paget disease and GCT. There was no evidence of malignancy. The
      clinicopathologic features of this rare lesion are described and correlated with
      a review of the literature.

PMID- 17437101
TI  - Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma.
AB  - OBJECTIVE: The objective was to elucidate clinical and imaging features of
      skeletal involvement, recurrences, and metastases of extraskeletal myxoid
      chondrosarcoma. MATERIALS AND METHODS: Included in this series are 4 patients,
      aged 44 to 65 years, 3 of whom were men and 1 a woman. RESULTS: The primary
      lesions were in the thigh (n = 3) and the upper arm (n = 1). Three patients with
      multiple metastases died of the disease, 2 were considered to have local
      recurrence in the adjacent bone. Skeletal metastases occurred after lung
      metastases in 2 cases, and before lung metastases in 1 case. Typical imaging
      findings are well-defined lesions with no sclerotic margin or matrix
      mineralization. A slow, but persistent growth is noted on the imaging features.
      CONCLUSION: Although skeletal metastases of chondrosarcoma of bone and soft
      tissue are rare, myxoid chondrosarcomas, currently classified tumors of uncertain
      differentiation, rarely metastasize and/or recur in the bones. The imaging
      features are typically of a localized lesion with cortical disruption or
      expansion.

PMID- 17437102
TI  - Cortico-medullary continuity in bizarre parosteal osteochondromatous
      proliferation mimicking osteochondroma on imaging.
AB  - Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is
      an unusual surface-based lesion of bone found most commonly in the hands and
      feet. In the original description of the lesion and in all publications that
      followed, one of the key imaging characteristics used to define this entity was
      the lack of cortico-medullary continuity with the underlying bone. The authors
      present 4 unique cases of pathologically proven BPOP in which cortico-medullary
      continuity with the underlying bone was demonstrated on imaging. It is believed
      that florid reactive periostitis, BPOP and turret osteochondroma may reflect
      points along the same continuum with trauma the likely inciting event. The
      authors suggest that, given this continuum, it may be possible to have BPOP
      lesions demonstrating overlapping imaging features with osteochondroma. If this
      is the case, strict adherence to the standard imaging criterion of lack of
      continuity between the lesion and the underlying bone may lead to misdiagnosis of
      these unusual cases of BPOP as osteochondromas.

PMID- 17437103
TI  - Radiographic measures of thoracic kyphosis in osteoporosis: Cobb and vertebral
      centroid angles.
AB  - OBJECTIVE: Several measures can quantify thoracic kyphosis from radiographs, yet
      their suitability for people with osteoporosis remains uncertain. The aim of this
      study was to examine the validity and reliability of the vertebral centroid and
      Cobb angles in people with osteoporosis. DESIGN AND PATIENTS: Lateral radiographs
      of the thoracic spine were captured in 31 elderly women with osteoporosis.
      Thoracic kyphosis was measured globally (T1-T12) and regionally (T4-T9) using
      Cobb and vertebral centroid angles. Multisegmental curvature was also measured by
      fitting polynomial functions to the thoracic curvature profile. Canonical and
      Pearson correlations were used to examine correspondence; agreement between
      measures was examined with linear regression. RESULTS: Moderate to high intra-
      and inter-rater reliability was achieved (SEM = 0.9-4.0 degrees ). Concurrent
      validity of the simple measures was established against multisegmental curvature
      (r = 0.88-0.98). Strong association was observed between the Cobb and centroid
      angles globally (r = 0.84) and regionally (r = 0.83). Correspondence between
      measures was moderate for the Cobb method r = 0.72), yet stronger for the
      centroid method (r = 0.80). The Cobb angle was 20% greater for regional measures
      due to the influence of endplate tilt. CONCLUSIONS: Regional Cobb and centroid
      angles are valid and reliable measures of thoracic kyphosis in people with
      osteoporosis. However, the Cobb angle is biased by endplate tilt, suggesting that
      the centroid angle is more appropriate for this population.

PMID- 17437104
TI  - Comparison of 99mTc-annexin A5 with 18F-FDG for the detection of atherosclerosis
      in ApoE-/- mice.
AB  - PURPOSE: (99m)Tc-annexin A5, a marker of ongoing apoptosis, and (18)F-FDG, a
      marker of the increased metabolism of inflammatory cells, are supposed to be
      useful in the detection of metabolically active atheroma. This study reports a
      comparison of the intralesional distribution of these tracers in relation to
      lesion development in ApoE-/- mice. METHODS: Male ApoE-/- mice (n = 12-14/group)
      were maintained on a Western-type diet after the age of 5 weeks. At 25 weeks,
      (99m)Tc-annexin A5 or (18)F-FDG was injected and the aortas were harvested for
      autoradiography (ARG) and Oil Red O staining. Regional radioactivity accumulation
      was compared in relation to the Oil Red O staining score (ranging from 0 to 3, a
      semiquantitative parameter for evaluating lesion development). RESULTS: Both
      (99m)Tc-annexin A5 and (18)F-FDG showed preferential uptake into atherosclerotic
      lesions, with higher uptake levels for (18)F-FDG (mean, 56.07 %IDxkg/m(2)) than
      for (99m)Tc-annexin A5 (mean, 10.38 %IDxkg/m(2)). The regional uptake levels of
      each tracer correlated with the Oil Red O staining score (r = 0.65, p < 0.05 for
      (99m)Tc-annexin A5; r = 0.56, p < 0.05 for (18)F-FDG). The uptake ratios of
      advanced lesions (score >0.5) to early lesions (score <0.5) were significantly
      higher for (99m)Tc-annexin A5 than for (18)F-FDG (f = 4.73, p = 0.03).
      CONCLUSION: Both (99m)Tc-annexin A5 and (18)F-FDG accumulate in atherosclerotic
      lesions and correlate with the severity of each lesion. The higher absolute
      uptake levels of (18)F-FDG may be advantageous for lesion detection, whereas the
      preferential uptake of (99m)Tc-annexin A5 in advanced lesions may be a useful
      indicator of late-stage lesions or vulnerable plaque transformation.

PMID- 17437105
TI  - Regional CBF changes in Parkinson's disease: the importance of functional
      neuroimaging analyses.

PMID- 17437107
TI  - FDOPA PET has clinical utility in brain tumour imaging: a proposal for a revision
      of the recent EANM guidelines.

PMID- 17437108
TI  - Regional CBF changes in Parkinson's disease: a correlation with motor
      dysfunction.
AB  - PURPOSE: The purpose of this study was to further localize cerebral perfusion
      abnormalities, and to better correlate these abnormalities with the clinical
      severity of Parkinson's disease (PD). METHODS: A single-photon emission computed
      tomography (SPECT) study was performed on 27 patients with PD and 24 age-matched
      controls. SPECT images were spatially normalized, concatenated, and then
      decomposed using Infomax independent component analysis (ICA). The resulting
      image components were separated by logistic regression into two subspaces:
      "disease-related" components whose subject weights differed between groups, and
      "disease-unrelated" components. The resultant regional cerebral blood flow (rCBF)
      subspace images were normalized to global CBF for each subject, and then
      processed using statistical parametric mapping to compare rCBF values between PD
      and control subjects. RESULTS: In the disease-related image subspace, patients
      with PD exhibited significantly higher adjusted rCBF in the putamen, globus
      pallidum, thalamus, brainstem, and the anterior lobe of the cerebellum, and
      significant hypoperfusion in the parieto-temporo-occipital cortex, the
      dorsolateral prefrontal cortex, the insula, and the cingulate gyrus. The motor
      Unified Parkinson's Disease Rating Scale scores correlated negatively with rCBF
      in the insula and cingulate gyrus. In the disease-unrelated image subspace, no
      brain voxels exhibited a significant group difference. CONCLUSION: ICA-based
      separation of normalized images into disease-related and disease-unrelated
      subspaces revealed many disease-related group blood flow differences. The regions
      revealed by ICA are consistent with the current model of PD. These rCBF changes
      in PD have not been fully demonstrated in any single functional imaging study
      previously.

PMID- 17437109
TI  - Ideal entry point for the thoracic pedicle screw during the free hand technique.
AB  - We have attempted to determine the spatial orientation of the base of the
      superior articular process in relation to the centre of the pedicle and then
      measure the transverse and sagittal screw angles using this ideal pedicle screw
      entry point - the base of the superior articular process at the junction of the
      lateral one-third and medial two-thirds. The proposed advantages of this
      technique are the easily identifiable entry point, the well-defined transverse
      and sagittal screw angles and a very low incidence of medial and inferior pedicle
      violation.

PMID- 17437110
TI  - Comparative analysis of pedicle screw versus hybrid instrumentation in adolescent
      idiopathic scoliosis surgery.
AB  - The expectations of both the patient and surgeon have been greatly revised in the
      last 10 years with the introduction of pedicle screws (PS) in spinal surgery. In
      this study, we have retrospectively evaluated and compared the results of PS
      instrumentation and the Hybrid System (HS), the latter consists of pedicle
      screws, sublaminar wire and hooks. The mean follow-up period was 60.1 months
      (range: 49-94 months) for the patients of the HS group and 29.3 months (range: 24
      35 months) for those of the PS group. In the HS group, pedicle screws were used
      at the thoracolumbar junction and lumbar vertebra, the bilateral
      pediculotransverse claw hook configuration was used at the cranial end of the
      instrumentation, sublaminar wire was used on the concave side of the apical
      region and the compressive hook was used on the convex side. In the PS group, PS
      were used on the concave sides at all levels and on the convex side of the
      cranial and caudal end of instrumentation, in the transition zone and at the
      apex. The two groups were comparable for variables such as mean age, preoperative
      Cobb angle, thoracic kyphosis angle, lordosis angle, coronal balance, flexibility
      of the curve, apical vertebra rotation (AVR), apical vertebra rotation (AVT) and
      the number of vertebrae included in the fusion (p>0.05). The parameters of values
      of correction, ratio of correction loss, AV derotation, AVT correction ratio,
      amount of blood loss, operation time, postoperative global coronal and sagittal
      balance, thoracic kyphosis angle and lumbar lordosis angle were measured at the
      last follow-up and used for comparing the HS and PS groups. There was no
      statistically significant difference between the groups for correction ratio,
      postoperative coronal balance, postoperative thoracic kyphosis and lumbar
      lordosis angle, operation time, amount of blood loss and number of fixation
      points (p>0.05) The difference for the ratio of correction loss, AV derotation
      angle and the AVT correction ratio at the last follow-up visit and for the total
      follow-up period between the groups was found to be statistically significant
      (p<0.05). Although it is possible to obtain a similar amount of correction by
      either instrumentation system, the loss of correction seems to be lower with the
      more rigid PS construction. The PS system also has a stronger effect on vertebral
      bodies, thereby providing better AV de-rotation. There was no significant
      difference (p>0.05) between the groups in terms of correction rate, postoperative
      coronal and sagittal balance, operation time, blood loss and number of fixation
      points. This may indicate that anchor points are more important than the use--or
      not--of screws. Correction durability and AV de-rotation was better with PS
      instrumentation, while AVT was better corrected by HS instrumentation (p<0.05).
      We propose that the reason for the better correction of AVT with HS
      instrumentation is the forceful translation offered by the sublaminar wire at the
      apical region, while the reason for the better correction durability of the PS
      instrumentation may be due to the fact that multiple pedicle screws which afford
      three-column control are better at maintaining the correction and preventing late
      deterioration.

PMID- 17437111
TI  - Kinetics of CXCR-4 and adhesion molecule expression during autologous stem cell
      mobilisation with G-CSF plus AMD3100 in patients with multiple myeloma.
AB  - AMD3100, a competitive antagonist of CXCR-4, disrupts the binding of its ligand,
      stromal cell-derived factor-1 (SDF-1), and facilitates stem cell mobilisation in
      patients with haematological malignancies. This study investigated the
      differential kinetics of CXCR-4 and adhesion molecule expression and their impact
      on stem cell yield during mobilisation with granulocyte-colony stimulating factor
      (G-CSF) (days 1-4) followed by AMD3100 in 10 patients with multiple myeloma. A
      four-colour flow cytometry-based determination of CXCR-4, VLA-4, L-selectin,
      PECAM, LFA-1 and CD44 expression on CD34+ cells and measurement of SDF-1
      concentration were performed at different time points. After G-CSF alone, CXCR-4
      expression on patients' blood and marrow CD34+ cells was significantly lower than
      in the healthy controls (p < 0.001), but allowed no prediction of stem cell
      yield. Except in the single poorly mobilising patient, AMD3100 led to a further
      significant decrease of CXCR4 (p = 0.001), which inversely correlated with the
      CD34+ counts in the blood (p = 0.005). SDF-1 level in patients' marrow was
      positively correlated with CXCR-4 expression on CD34+ cells (p = 0.011). It is
      interesting to note that the expression of adhesion molecules remained unaffected
      by AMD3100 administration. Further studies will define the possible prognostic
      role of AMD3100 mediated changes in CXCR-4 expression for the prediction of stem
      cell yield attainable with this new mobilisation regimen.

PMID- 17437112
TI  - Suboptimal doses of low molecular weight heparin and acute venous
      thromboembolism. Data from the RIETE registry.
AB  - The objective was to assess the use of suboptimal doses (60-149 UI kg(-1) day(
      1)) of low molecular weight heparin (LMWH) in the treatment of acute venous
      thromboembolism (VTE) in actual clinical practice and to evaluate the outcomes
      compared to standard doses (> or = 150 UI kg(-1) day(-1)). Retrospective analysis
      of data from a multicenter registry of patients with VTE (RIETE; Registro
      Informatizado de Enfermedad TromboEmbolica). Patient characteristics,
      antithrombotic treatments, and 3-month outcomes were analyzed. We studied 12,302
      patients with VTE; 10,524 patients were treated initially only with LMWH; 1,547
      patients received suboptimal LMWH (mean = 122 UI kg(-1) day(-1)), and 8,977
      patients received full-dose LMWH (mean = 191 UI kg(-1) day(-1)). The suboptimal
      group included significantly more patients with recent major bleeding, weight
      more than 100 kg, raised creatinine, or deep vein thrombosis. No significant
      differences in mortality rate (7.7 vs 7.8%), VTE recurrence (2.7 vs 2.3%), or
      fatal hemorrhage (0.6 vs 0.6%) occurred between the suboptimal and the standard
      group. Major bleeding episodes occurred more frequently in the patients with
      pulmonary embolism treated with suboptimal LMWH (4.5 vs 2.4%; p = 0.02). In the
      multivariate analysis, after adjusting for bleeding risk factors, major
      hemorrhage was not associated with the heparin dose. Suboptimal doses of LMWH are
      used in actual clinical practice in a reduced group of patients at an outcome
      rate not very different to that of standard doses. Bleeding episodes depend more
      on the patient's characteristics than on the LMWH dose. Randomized trials should
      be performed to corroborate these results.

PMID- 17437113
TI  - Overexpression of AeNHX1, a root-specific vacuolar Na+/H+ antiporter from
      Agropyron elongatum, confers salt tolerance to Arabidopsis and Festuca plants.
AB  - Agropyron elongatum, a species in grass family, has a strong tolerance to salt
      stress. To study the molecular mechanism of Agropyron elongatum in salt
      tolerance, we isolated a homolog of Na(+)/H(+) antiporters from the root tissues
      of Agropyron plants. Sequence analysis revealed that this gene encodes a putative
      vacuolar Na(+)/H(+) antiporter and was designated as AeNHX1. The AeNHX1-GFP
      fusion protein was clearly targeted to the vacuolar membrane in a transient
      transfection assay. Northern analysis indicated that AeNHX1 was expressed in a
      root-specific manner. Expression of AeNHX1 in yeast Na(+)/H(+) antiporter mutants
      showed function complementation. Further, overexpression of AeNHX1 promoted salt
      tolerance of Arabidopsis plants, and improved osmotic adjustment and
      photosynthesis which might be responsible for normal development of transgenic
      plants under salt stress. Similarly, AeNHX1 also functioned in transgenic Festuca
      plants. The results suggest that this gene might function in the roots of
      Agropyron plants, and its expression is involved in the improvement of salt
      tolerance.

PMID- 17437114
TI  - Wide hilar hepaticojejunostomy: the optimum method of reconstruction after
      choledochal cyst excision.
AB  - Standard reconstruction after choledochal cyst excision is by Roux-en-Y
      hepaticojejunostomy to the common hepatic duct. Long-term follow up studies have
      shown a 10% incidence of late complications, including anastomotic stricture. By
      extending the bilio-enteric anastomosis along the left hepatic duct, a wide hilar
      bilio-enteric anastomosis is created which may help to minimize late anastomotic
      complications. Forty-one consecutive patients (24 girls, 18 infants) with a
      median age of 2.3 years (range 44 days to 15.6 years) and median weight 11.5 kg
      (range 2.1-59 kg) underwent radical choledochal cyst excision with a wide hilar
      hepaticojejunostomy. Thirty-eight were followed-up both clinically and by
      ultrasound scan and biochemical liver function tests for a median of 2.7 years
      (range 0.1-12.5 years). The median width of the hilar hepaticojejunostomy was 8
      mm (range 6-25 mm) in 18 infants, and 15 mm (range 10-25 mm) in 22 older
      children. In one patient it was not measured. Only one surgical complication
      occurred--a self-limiting bile leak which settled spontaneously. Median
      postoperative stay was 6 days (range 5-21 days). No patient has had an episode of
      cholangitis or adhesive small bowel obstruction to date. Postoperative
      biochemical liver function tests have remained normal in all but one child (with
      pre-existing biliary cirrhosis). After radical resection of a choledochal cyst, a
      wide hilar hepaticojejunostomy is a, safe, effective and durable reconstructive
      technique that can be performed at any age and may help to minimize the long-term
      risk of complications.

PMID- 17437115
TI  - Congenital esophageal stenosis associated with esophageal atresia: new concepts.
AB  - Congenital esophageal stenosis (CES) is suspected by a fixed intrinsic narrowing
      of the esophagus that affects the normal swallowing mechanism. The diagnosis is
      only confirmed by histopathologic picture, which may show fibromuscular disease
      (FMD) or tracheobronchial remnants (TBR). The latter involves ciliated pseudo
      stratified columnar epithelium, seromucous glands or cartilage each alone or in
      combination. The aim of this study is to document the usefulness of histologic
      picture of surgical specimens obtained from the lower esophageal pouch (LEP)
      during primary repair in detecting cases of CES associated with esophageal
      atresia (EA) with or without tracheoesophageal fistula (TEF). Over an 8-year
      period, 57 consecutive cases operated upon for EA with or without TEF were
      subjected for histologic examination of surgical specimens obtained from the tip
      of the LEP. Cases that histologically showed FMD or TBR were included. The
      usefulness of this histologic picture as a diagnostic and therapeutic aid is
      assessed. Methods of treatment and outcome were also reviewed. Eight patients out
      of 57 (14%) had a histologic picture suggestive of CES, two with FMD, four with
      TBR without cartilage and two with cartilage. Out of 57 patients, 23 developed
      strictures, six of them had positive biopsies suggestive of CES. One patient with
      TBR without cartilage did not have stricture. Another case of pure atresia had
      LEP resection and gastric pull up showed cartilage involving the whole lower
      esophagus. Excluding the case of pure EA with gastric pull up, all patients
      suffered from feeding problems and recurrent aspiration. Fluoroscopic barium
      studies showed late onset minor dysmotility in five patients and late onset major
      dysmotility in two. All cases studied showed significant gastro-esophageal reflux
      (GER). Stricture was seen at the anastomotic site extending distally in the two
      fibromuscular cases and one case with cartilage, at the anastomotic site in three
      cases with TBR without cartilage. Anti reflux surgical procedures were performed
      in four patients without benefit in two patients with major dysmotility.
      Dilatation was successful in the three patients with TBR without cartilage. One
      patient with cartilage had resection of the anastomotic site and required
      frequent dilatations and is now doing well. A case of FMD did not improve after
      frequent dilatations and myotomy together with Nissen's fundoplication and
      required resection while the other case of FMD responded partially to
      dilatations. Cartilage in cases of CES requires surgical resection. Those with
      TBR without cartilage may not develop stricture. If stricture develops, it
      responds well to dilatation and patients have good clinical outcomes. Unlike
      isolated CES, GER is a significant feature in CES with EA. Anti reflux procedures
      should be avoided before definitive surgery for the stricture and if necessary a
      partial wrap with gastrostomy is recommended. CES should be considered in the
      etiology of anastomotic stricture. Taking a surgical specimen routinely from the
      tip of the LEP during primary esophageal repair for histologic studies is highly
      recommended.

PMID- 17437116
TI  - Amelanotic spitzoid melanoma in a prepubescent boy.
AB  - The diagnosis of malignant melanoma (MM) in children is difficult due to its
      uncommon occurrence as well histological similarities to Spitz nevus. A case of
      MM of the foot in an 11-year-old boy is reported illustrating the histological
      overlap between Spitz nevus and MM. In our patient, both the primary foot lesion
      and the regional inguinal metastases were amelanotic, further increasing the
      diagnostic difficulty. The literature on MM in children is limited and the
      documentation of such unusual cases is necessary to improve the knowledge on this
      disease.

PMID- 17437117
TI  - Biliary atresia: interdisciplinary initiatives focus on a rare disease.
AB  - During the last decade, biliary atresia (BA) has attained more interest and the
      frequency of BA-related publications has increased continuously. Pediatric
      hepatologists and pediatric surgeons are very active in improving diagnosis and
      treatment modalities of BA patients, in order to prolong the survival rate of
      their native liver. Together with transplant surgeons, the bridging of BA
      patients to liver transplantation (LTx) becomes optimized and as a consequence of
      this interdisciplinary approach, the overall survival of babies with BA has
      already reached 90%. Furthermore, basic research into the still unknown origin of
      BA has advanced, and numerous scientific programs have already linked together.
      The overriding interest is to discover at least BA's etiology and to turn the
      treatment of BA patients from a symptomatic to a causative approach.
      Interdisciplinary and international programs are mandatory and already existing
      initiatives in Europe, the United States and Japan are going to coordinate their
      registries, clinical trials and basic research studies for the benefit of the
      patients and solve the riddle of BA.

PMID- 17437118
TI  - The use of Surgisis for abdominal wall reconstruction in the separation of
      omphalopagus conjoined twins.
AB  - Abdominal wall reconstruction in omphalopagus twins poses a difficult
      reconstructive challenge, as separation often results in a large abdominal wall
      defect. A number of options are available for closure, including tissue flaps,
      expanders and patches made of foreign material. Surgisis is a new biodegradable
      small intestine scaffolding substrate that permits tissue in-growth and results
      in a permanent durable scar. We describe its use in abdominal wall reconstruction
      after separation of a set of conjoined twins. A set of omphalopagus conjoined
      twins shared liver and abdominal wall. After separation at 6 months of age, Twin
      A's abdomen could be closed primarily, but Twin B could not. A 4-ply Surgisis
      mesh was used in the upper abdominal closure, and a skin flap was created, to
      completely cover the patch. Both twins survived the operation. A small portion of
      the skin flap over the Surgisis broke down, healing by secondary intention. In
      follow up of over 18 months post procedure, there have been no wound infections
      and the abdominal wall is intact with no evidence of a hernia. Surgisis can be
      successfully used for the reconstruction of complex abdominal wall defects in the
      pediatric patient, including reconstruction after separation of conjoined twins.

PMID- 17437119
TI  - Involvement of P38 MAP kinase in the augmentation of UVB-mediated apoptosis via
      the epidermal platelet-activating factor receptor.
AB  - Platelet-activating factor (PAF) is a group of phosphocholines with various
      biological effects, which are mediated by the PAF receptor (PAF-R). Our previous
      studies have demonstrated that ultraviolet B radiation (UVB) is a potent stimulus
      for PAF production, and that the presence of the PAF-R on epithelial cells
      results in an augmentation of UVB-induced apoptosis. Inasmuch as PAF-R activation
      results in numerous signal transduction pathways, the present study was designed
      to characterize the signal transduction pathway responsible for PAF-R-mediated
      enhanced UVB-induced cytotoxicity. Using a model system of PAF-R-negative and 
      positive epithelioid KB cells, we demonstrate that inhibitors of p38 MAP kinase
      block the augmentation of UVB-mediated apoptosis seen in PAF-R-positive KB cells.
      In contrast, pharmacological and/or molecular inhibition of other pathways linked
      to PAF-R activation including ERK MAP kinase and NFkappaB do not affect PAF-R
      mediated cytotoxicity. This study demonstrates the important role that p38 MAP
      kinase plays in PAF-R-mediated augmentation of UVB cytotoxicity.

PMID- 17437120
TI  - Skull base surgery for malignancy: when not to operate.
AB  - The purpose of this paper is to detail the contraindications for surgery, with
      curative intent for those patients who suffer from a head and neck malignancy
      that invades the intracranial space. This is based on a 30-year experience of
      over 250 patients. The most important contraindications are anatomical. Surgery
      is not done if the following structures are invaded: brain stem, eloquent
      portions of the cerebrum, superior sagittal sinus, both internal carotid
      arteries, both cavernous sinuses and certain vital bridging veins. Certain tumor
      factors are absolute but are occasionally relative contraindications: such as
      distant metastatic disease especially if multiple and at multiple anatomic sites.
      Some tumors that behave in a particularly virulent fashion that defy complete
      resection but are often difficult to predict preoperatively. Lack of patient
      medical fitness or absence of patient commitment to the operative procedure is
      make-up two serious contraindications to surgery.

PMID- 17437121
TI  - Magnetic resonance imaging of the clavicular ossification.
AB  - Assessment of the degree of ossification of the medial clavicular epiphyseal
      cartilage is of vital importance in forensic age diagnostics of living
      individuals aged more than 18 years. To date, reference studies on the assessment
      of clavicular ossification using imaging procedures only relate to conventional
      radiography and computed tomography (CT). In this study, magnetic resonance (MR)
      scans of 54 sternoclavicular joints of bodies aged between 6 and 40 years were
      evaluated prospectively. All of the examined medial clavicular epiphyseal
      cartilages permitted an assessment of the degree of ossification. Stage 2 was
      first observed at the age of 15.0 years, the earliest age at which stage 3 was
      observed was 16.9 years, and stage 4 was first observed at the age of 23.8 years.
      The observed age intervals of the respective degrees of ossification correspond
      to the known data from X-ray and CT scan examinations. The achieved results
      should be examined with a larger number of cases. A modified examination protocol
      is required for the MR examination of the medial clavicular epiphyseal cartilage
      for the purpose of forensic age diagnostics of living individuals.

PMID- 17437122
TI  - Long-term follow-up of polypoidal choroidal vasculopathy after photodynamic
      therapy with verteporfin.
AB  - PURPOSE: To report on the clinical features of three cases of polypoidal
      choroidal vasculopathy (PCV) during long-term follow-up after photodynamic
      therapy (PDT). DESIGN: Interventional case reports. METHODS: Among the
      participants in the Japanese Age-Related Macular Degeneration Trial (JAT) at our
      hospital, a PCV was seen in three eyes at baseline on retrospective analysis of
      indocyanine green angiography (ICGA) using fundus camera. We report the clinical
      features of these cases during more than 4 years follow-up. RESULTS: The mean
      number of PDT treatments was 5.7. Improved visual acuity (VA) and cessation of
      fluorescein leakage was achieved within 18 months in all eyes; however,
      subretinal hemorrhage and subfoveal fluid recurred due to new or recurrent PCV.
      The final VA decreased markedly in two eyes. CONCLUSIONS: The eyes with PCV,
      which had been treated successfully with PDT, may have developed new or recurrent
      PCV during long-term follow-up. Periodical ICGA would be needed to detect
      abnormal choroidal vascular changes.

PMID- 17437123
TI  - Bevacizumab (Avastin) treatment in patients with retinal angiomatous
      proliferation.
AB  - AIM: To determine the anatomical and functional outcome after injection of
      bevacizumab (Avastin, Genentech) in eyes with retinal angiomatous proliferation
      (RAP). DESIGN: Prospective interventional case series. METHODS: Sixteen eyes of
      16 consecutive patients with visual loss due to RAP underwent intravitreal
      injections of 1.25 mg (0.05 ml) bevacizumab. Best corrected visual acuity
      testing, fluorescein and ICG-angiography as well as OCT imaging were performed at
      baseline and at each follow-up visit within a 3-month period. RESULTS: Mean
      visual acuity pre-injection was 0.68 +/- 0.36 logMAR (n = 16), mean reading
      ability 0.58 +/- 0.26 logRAD (n = 11). Far vision increased significantly by a
      mean of 1.7 +/- 2 lines 4 weeks after the injection (p = 0.004), as did reading
      (0.6 +/- 2.3 lines, p > 0.05). Both remained stable up to 3 months. Central
      retinal thickness decreased from 367 +/- 112 microm (mean+/-SD) to 272 +/- 123
      microm 3 months after injection (p = 0.006). Leakage decreased angiographically
      in 12 eyes (75%) and remained stable in four eyes (25%). Re-injection of
      bevacizumab within the 3-month follow-up period was performed once in eight eyes,
      and twice in one eye. No adverse events were observed. CONCLUSION: Intravitreal
      bevacizumab (Avastin) resulted in a reduction of leakage, intra- and subretinal
      fluid. An increase in visual acuity was seen already 4 weeks after first
      injection. However, a complete occlusion of feeder vessels could not be achieved
      within this 3-month period. Randomized clinical trials would be required to
      evaluate dose and frequency of injections and possible beneficial effects of
      combination therapies, as well as the long-term results.

PMID- 17437124
TI  - Progression detection in glaucoma can be made more efficient by using a variable
      interval between successive visual field tests.
AB  - BACKGROUND: This study aimed to gain insight into the optimal spacing in time for
      visual field tests for progression detection in glaucoma. METHODS: Three
      perimetric strategies for progression detection were compared by means of
      simulation experiments in a theoretical cohort. In strategies 1 and 2, visual
      field testing was performed with fixed-spaced inter-test intervals, using
      intervals of 3 and 6 months respectively. In strategy 3, the inter-test interval
      was kept at 1 year as long as the fields appeared unchanged. Then, as soon as
      progression was suspected, confirmation or falsification were performed promptly.
      Follow-up fields were compared against a baseline assuming linear deterioration,
      using various progression criteria. Outcome measures were: (1) specificity, (2)
      time delay until the diagnosis of definite progression, and (3) number of
      required tests. RESULTS: Strategies 2 and 3 had a higher specificity than
      strategy 1. Strategies 1 and 3 detected progression earlier than strategy 2. The
      number of required visual field tests was lowest for strategy 3. CONCLUSION:
      Perimetry in glaucoma can be optimised by postponing the next test under
      apparently stable field conditions and bringing the next test forward once
      progression is suspected.

PMID- 17437125
TI  - Efficacy and safety of intravenous injection of lidocaine in the treatment of
      acute primary angle-closure glaucoma: a pilot study.
AB  - AIMS: To study the safety and effectiveness of a combination of both intravenous
      injection of lidocaine and intraocular pressure-lowering medications, in the
      intraocular pressure control and relief of symptoms of refractory acute primary
      angle-closure glaucoma (PACG). METHODS: Five consecutive patients with their
      first attack of acute PACG, with intraocular pressure > or = 45 mmHg and a
      failure to release from the attack under antiglaucomatous medications for 4
      hours, were recruited into the study. On presentation, each patient received
      topical pilocarpine and timolol, and systemic acetazolamide and mannitol as
      primary treatment. Then the patients accepted 2% lidocaine by intravenous
      injection at dose of 0.8 mg/kg in concert with antiglaucomatous medications. The
      intraocular pressures after intravenous injection at 30 minutes, and then at 1,
      2, 4, 12, and 24 hours, were documented by applanation tonometry. Symptoms,
      visual acuity, intraocular pressure, corneal edema, angle status on gonioscopy,
      pupillary size, and reaction were also measured. RESULTS: Six eyes of five
      patients seen with acute PACG were recruited. The mean intraocular pressure was
      reduced from 50.83 +/- 5.34 mmHg to 39.5 +/- 3.45 mmHg at 30 minutes after
      intravenous injection, and then to 33.3 +/- 3.56 mmHg at 1 hour, and 24.55 +/-
      5.09 mmHg at 2 hours after intravenous injection. The mean intraocular pressure
      was less than 21 mmHg at 4 hours and beyond. There was instant symptomatic relief
      for all patients. No complications were encountered. CONCLUSIONS: From this
      preliminary study, intravenous injection of lidocaine seems to be safe and
      effective in controlling intraocular pressure and eliminating symptoms in acute
      PACG. But the exact efficacy and safety need further investigation in large case
      studies.

PMID- 17437126
TI  - A quantitative analysis of the effect of cycle length on arrhythmogenicity in
      hypokalaemic Langendorff-perfused murine hearts.
AB  - The clinically established proarrhythmic effect of bradycardia and antiarrhythmic
      effect of lidocaine (10 microM) were reproduced in hypokalaemic (3.0 mM K(+))
      Langendorff-perfused murine hearts paced over a range (80-180 ms) of baseline
      cycle lengths (BCLs). Action potential durations (at 90% repolarization,
      APD(90)s), transmural conduction times and ventricular effective refractory
      periods (VERPs) were then determined from monophasic action potential records
      obtained during a programmed electrical stimulation procedure in which
      extrasystolic stimuli were interposed following regular stimuli at successively
      decreasing coupling intervals. A novel graphical analysis of epicardial and
      endocardial, local and transmural relationships between APD(90), corrected for
      transmural conduction time where appropriate, and VERP yielded predictions in
      precise agreement with the arrhythmogenic findings obtained over the entire range
      of BCLs studied. Thus, in normokalaemic (5.2 mM K(+)) hearts a statistical
      analysis confirmed that all four relationships were described by straight lines
      of gradients not significantly (P > 0.05) different from unity that passed
      through the origin and thus subtended constant critical angles, theta with the
      abscissa (45.8 degrees +/- 0.9 degrees , 46.6 degrees +/- 0.5 degrees , 47.6
      degrees +/- 0.5 degrees and 44.9 degrees +/- 0.8 degrees , respectively).
      Hypokalaemia shifted all points to the left of these reference lines,
      significantly (P < 0.05) increasing theta at BCLs of 80-120 ms where arrhythmic
      activity was not observed ( approximately 63 degrees , approximately 54 degrees ,
      approximately 55 degrees and approximately 58 degrees , respectively) and further
      significantly (P < 0.05) increasing theta at BCLs of 140-180 ms where arrhythmic
      activity was observed ( approximately 68 degrees , approximately 60 degrees ,
      approximately 61 degrees and approximately 65 degrees , respectively). In
      contrast, the antiarrhythmic effect of lidocaine treatment was accompanied by a
      significant (P < 0.05) disruption of this linear relationship and decreases in
      theta in both normokalaemic ( approximately 40 degrees , approximately 33 degrees
      , approximately 39 degrees and approximately 41 degrees , respectively) and
      hypokalaemic ( approximately 40 degrees , approximately 44 degrees ,
      approximately 50 degrees and approximately 48 degrees , respectively) hearts.
      This extended a previous approach that had correlated alterations in transmural
      repolarization gradients with arrhythmogenicity in murine models of the
      congenital long QT syndrome type 3 and hypokalaemia at a single BCL. Thus, the
      analysis in terms of APD(90) and VERP provided a more sensitive indication of the
      effect of lidocaine than one only considering transmural repolarization gradients
      and may be particularly applicable in physiological and pharmacological
      situations in which these parameters diverge.

PMID- 17437128
TI  - Ecological release in lizard assemblages of neotropical savannas.
AB  - We compare lizard assemblages of Cerrado and Amazonian savannas to test the
      ecological release hypothesis, which predicts that niche dimensions and abundance
      should be greater in species inhabiting isolated habitat patches with low species
      richness (Amazonian savannas and isolated Cerrado patches) when compared with
      nonisolated areas in central Cerrado with greater species richness. We calculated
      microhabitat and diet niche breadths with data from 14 isolated Cerrado patches
      and Amazon savanna areas and six central Cerrado populations. Morphological data
      were compared using average Euclidean distances, and lizard abundance was
      estimated using the number of lizards captured in pitfall traps over an extended
      time period. We found no evidence of ecological release with respect to
      microhabitat use, suggesting that historical factors are better microhabitat
      predictors than ecological factors. However, data from individual stomachs
      indicate that ecological release occurs in these areas for one species
      (Tropidurus) but not others (Ameiva ameiva, Anolis, Cnemidophorus, and
      Micrablepharus), suggesting that evolutionary lineages respond differently to
      environmental pressures, with tropidurids being more affected by ecological
      factors than polychrotids, teiids, and gymnophthalmids. We found no evidence that
      ecological release occurs in these areas using morphological data. Based on
      abundance data, our results indicate that the ecological release (density
      compensation) hypothesis is not supported: lizard species are not more abundant
      in isolated areas than in nonisolated areas. The ecology of species is highly
      conservative, varying little from assemblage to assemblage. Nevertheless,
      increases in niche breadth for some species indicate that ecological release
      occurs as well.

PMID- 17437127
TI  - Both Hoxc13 orthologs are functionally important for zebrafish tail fin
      regeneration.
AB  - Hox genes are re-expressed during regeneration in many species. Given their
      important role in body plan development, it has been assumed, but not directly
      shown, that they play a functional role in regeneration. In this paper we show
      that morpholino-mediated knockdown of either Hoxc13a or Hoxc13b during the
      process of zebrafish tail fin regeneration results in a significant reduction of
      regenerative outgrowth. Furthermore, cellular proliferation within the blastema
      is directly affected in both knockdowns. Hence, similar to the demonstration of
      unique functions of multiple Hox genes during limb formation, both Hoxc13
      orthologs have distinct functions in regeneration.

PMID- 17437129
TI  - Focal and segmental glomerulosclerosis in children: a longitudinal assessment.
AB  - Recent data suggest that the histologic finding of focal and segmental
      glomerulosclerosis (FSGS) is increasing among children. There are, however,
      limited longitudinal pediatric data on prevalence, demographics, and steroid
      responsiveness in FSGS. We identified 201 consecutive nephrotic children
      diagnosed between 1977 and 2002 with 2 years follow-up; 51% had undergone renal
      biopsy due to steroid sequelae or resistance; 48 children with FSGS were
      diagnosed. Compared with non-FSGS children, FSGS children were older at diagnosis
      (6.9 years vs 4.4 years, P<0.02), more likely girls (54% vs 28%, P<0.02), Black
      or Hispanic (42% vs 16%, P<0.001), and the FSGS was more likely to be steroid
      resistant (73% vs 10%, P<0.001). To assess for longitudinal differences, we
      grouped children by presentation: pre-1985, between 1985 and 1995, and post-1995.
      There was no difference in proportion of children biopsied or diagnosed with FSGS
      during each interval. Among FSGS children, there was no difference in racial or
      gender composition in each period, but there was a difference in age at diagnosis
      (2.6 vs 5.7 vs 8.5 years; P=0.01), also observed in the non-FSGS children (2.2 vs
      3.9 vs 4.9 years; P=0.02). In contradistinction to non-FSGS children, there was a
      marked increase in steroid resistance with FSGS (43% vs 62% vs 86%; P=0.03).

PMID- 17437130
TI  - Glomerular eNOS gene expression during postnatal maturation and AT1 receptor
      inhibition.
AB  - Glomerular maturation increases from immature superficial to advanced
      juxtamedullary nephrons, while nephrogenesis continues postnatally in porcine
      kidneys. Endothelial NOS, eNOS, shows significant postnatal renal developmental
      regulation, perhaps mediated by Angiotensin II (AII). The objective was to
      compare eNOS mRNA gene expression between superficial and juxtamedullary
      glomeruli obtained from piglets and adult pigs utilizing laser capture
      microdissection during basal conditions and, to determine the role of the AII AT1
      receptor, AT1, after chronic AT1 inhibition (AT1X) with candesartan. Superficial
      glomerular eNOS expression was lowest in newborns (NB) and at 7 days, and was
      highest in 14, 21 day old piglets and adults. Juxtamedullary glomerular eNOS,
      while similar in NB, 14, 21 day and adult, dipped to the lowest level at 7 days.
      Juxtamedullary glomerular eNOS expression in the NB was 7 fold greater than in
      superficial glomeruli. AT1X did not change eNOS expression in adult glomeruli.
      AT1X significantly reduced NB eNOS expression in both superficial, 90+/-10%, and
      juxtamedullary glomeruli, 89+/-5% respectively. In conclusion, eNOS gene
      expression demonstrates significant differences between NB superficial and
      juxtamedullary glomeruli, significant postnatal developmental regulation of both
      glomerular locations, and this expression may be mediated in the NB by AII via
      the AT1 receptor.

PMID- 17437131
TI  - Normative blood pressure data in the early neonatal period.
AB  - There has been a temporal trend towards increased birth weight over the past
      three decades. This increase in birth weight may have resulted in an increase in
      neonatal blood pressure. Neonatal hypertension is becoming more common,
      especially in neonatal intensive care unit survivors. Current normative values
      are required to assist in diagnosis and appropriate management of neonatal
      hypotension and hypertension. The objective of this study was to determine
      normative blood pressure readings in healthy term neonates. Term neonates from
      the postnatal ward were enrolled from August 2003 to August 2005. Exclusion
      criteria included infants of mothers with preeclampsia, hypertension of any
      cause, gestational diabetes, type 1 diabetes mellitus and illicit substance use,
      infant congenital or chromosomal anomaly, admission to the neonatal intensive
      care unit or possible sepsis. Of the 406 infants enrolled, 218 were male. The
      median systolic, diastolic and mean blood pressures on day 1 of life were 65
      mmHg, 45 mmHg, and 48 mmHg, respectively. On day 4, these values had increased to
      70 mmHg, 46 mmHg and 54 mmHg. There was a significant elevation in blood pressure
      from day 1 to day 2 of life. There was no significant difference in blood
      pressure readings with respect to birth weight or length. The only significant
      difference between the sexes was a lower mean and diastolic pressure on day 2 in
      boys. This study has provided current normative blood pressure readings of
      healthy term neonates that can be used to assess both hypotension and
      hypertension in the term neonate. No increase in blood pressure was noted from
      previous studies.

PMID- 17437132
TI  - Genetic approaches to human renal agenesis/hypoplasia and dysplasia.
AB  - Congenital abnormalities of the kidney and urinary tract are frequently observed
      in children and represent a significant cause of morbidity and mortality. These
      conditions are phenotypically variable, often affecting several segments of the
      urinary tract simultaneously, making clinical classification and diagnosis
      difficult. Renal agenesis/hypoplasia and dysplasia account for a significant
      portion of these anomalies, and a genetic contribution to its cause is being
      increasingly recognized. Nevertheless, overlap between diseases and challenges in
      clinical diagnosis complicate studies attempting to discover new genes underlying
      this anomaly. Most of the insights in kidney development derive from studies in
      mouse models or from rare, syndromic forms of human developmental disorders of
      the kidney and urinary tract. The genes implicated have been shown to regulate
      the reciprocal induction between the ureteric bud and the metanephric mesenchyme.
      Strategies to find genes causing renal agenesis/hypoplasia and dysplasia vary
      depending on the characteristics of the study population available. The
      approaches range from candidate gene association or resequencing studies to
      traditional linkage studies, using outbred pedigrees or genetic isolates, to
      search for structural variation in the genome. Each of these strategies has
      advantages and pitfalls and some have led to significant discoveries in human
      disease. However, renal agenesis/hypoplasia and dysplasia still represents a
      challenge, both for the clinicians who attempt a precise diagnosis and for the
      geneticist who tries to unravel the genetic basis, and a better classification
      requires molecular definition to be retrospectively improved. The goal appears to
      be feasible with the large multicentric collaborative groups that share the same
      objectives and resources.

PMID- 17437133
TI  - Hyperostosis with hyperphosphatemia and tumoral calcinosis: a case report.
AB  - The combination of hyperostosis and hyperphosphatemia is very rare. In this case
      report, we present a boy with a combination of diffuse hyperostosis and
      hyperphosphatemia. We evaluated most possible known causes of hyperphosphatemia
      and hyperostosis. He had normal renal function and serum parathormone level.
      Concerning some few similar cases, most of them from Middle Eastern countries, we
      present this combination (diffuse hyperostosis and hyperphosphatemia) as a new
      syndrome to be discussed in pediatric textbooks.

PMID- 17437134
TI  - Chronic glomerulonephritis associated with IgG subclass deficiency.
AB  - We experienced two patients with IgG subclass deficiency who suffered from
      chronic glomerulonephritis (GN). Patient 1 was a 17-year-old girl with IgG
      subclass deficiency (combined deficiency of IgG2 and IgG4). Renal biopsy was
      performed when she was aged 16 years, and she was diagnosed with
      membranoproliferative GN. Patient 2 was a 16-year-old girl with IgG subclass
      deficiency (combined deficiency of IgG2, IgG3, and IgG4). Renal biopsy was
      performed when she was aged 15 years, and she was diagnosed with membranous
      nephropathy. We examined the glomerular deposition patterns of their IgG
      subclasses. Furthermore, we compared their clinical and laboratory findings with
      those of three patients with IgG subclass deficiency without GN. Patients with GN
      suffered infections more frequently than those without GN. The serum levels of
      IgG (especially IgG1) and IgM were higher in patients with GN than in those
      without GN. In patient 1 IgG1 and IgG3 were deposited in a mesangiocapillary
      pattern, but, in patient 2, only IgG1 was deposited in a capillary pattern. Thus,
      the different patterns of IgG subclass deficiency between the two patients may be
      responsible for their different glomerular pathologies. To the best of our
      knowledge, this is the first report of chronic GN in patients with IgG subclass
      deficiency.

PMID- 17437135
TI  - Gene flow in maize fields with different local pollen densities.
AB  - The development of maize (Zea mays L.) varieties as factories of pharmaceutical
      and industrial compounds has renewed interest in controlling pollen dispersal.
      The objective of this study was to compare gene flow into maize fields of
      different local pollen densities under the same environmental conditions. Two
      fields of approximately 36 ha were planted with a nontransgenic, white hybrid, in
      Ankeny, Iowa, USA. In the center of both fields, a 1-ha plot of a yellow-seeded
      stacked RR/Bt transgenic hybrid was planted as a pollen source. Before flowering,
      the white receiver maize of one field was detasseled in a 4:1 ratio to reduce the
      local pollen density (RPD). The percentage of outcross in the field with RPD was
      42.2%, 6.3%, and 1.3% at 1, 10, and 35 m from the central plot, respectively. The
      percentage of outcross in the white maize with normal pollen density (NPD) was
      30.1%, 2.7%, and 0.4%, respectively, at these distances. At distances greater
      than 100 m, the outcross frequency decreased below 0.1 and 0.03% in the field
      with RPD and NPD, respectively. A statistical model was used to compare pollen
      dispersal based on observed outcross percentages. The likelihood ratio test
      confirmed that the models of outcrossing in the two fields were significantly
      different (P is practically 0). Results indicated that when local pollen is low,
      the incoming pollen has a competitive advantage and the level of outcross is
      significantly greater than when the local pollen is abundant.

PMID- 17437136
TI  - Is there a sagittal imbalance of the spine in isthmic spondylolisthesis? A
      correlation study.
AB  - Recent studies suggested a predominant role of spinopelvic parameters to explain
      lumbosacral spondylolisthesis pathogeny. We compare the pelvic incidence and
      other parameters of sagittal spinopelvic balance in adolescents and young adults
      with developmental spondylolisthesis to those parameters in a control group of
      healthy volunteers. We compared the angular parameters of the sagittal balance of
      the spine in a cohort of 244 patients with a developmental L5-S1
      spondylolisthesis with those of a control cohort of 300 healthy volunteers. A
      descriptive and correlation study was performed. The L5 anterior slipping and
      lumbosacral kyphosis in spondylolisthesis patients was described using multiple
      regression analysis study. Our study demonstrates that the related measures of
      sagittal spinopelvic alignment are disturbed in adolescents and young adults with
      developmental spondylolisthesis. These subjects stand with an increased sacral
      slope, pelvic tilt and lumbar lordosis but with a decreased thoracic kyphosis.
      Pelvic incidence was significantly higher in spondylolisthesis patients as
      compared with controls but was not clearly correlated with the grade of slipping.
      We showed the same "sagittal balance strategy" in spondylolisthesis patients as
      in the control group regarding correlations between pelvic incidence, sacral
      slope, pelvic tilt and lumbar lordosis. We believe that the lumbosacral kyphosis
      is a stronger factor than pelvic incidence which need to be taken into account as
      a predominant factor in theories of pathogenesis of lumbosacral spondylolithesis.
      We thus believe that increased lumbar lordosis associated with L5-S1
      spondylolisthesis is secondary to the high pelvic incidence and is an important
      factor causing high shear stresses at the L5-S1 pars interarticularis. However,
      the "local" sagittal imbalance of the lumbosacral junction is compensated by
      adjacent mobile segments in the upper lumbar spine, the pelvis orientation and
      the thoracic spine. The result is not optimal but a satisfactory global sagittal
      balance of the trunk, even in the most severe grade of slipping.

PMID- 17437138
TI  - Experimental and theoretical investigations of spectroscopic properties of
      azobenzene derivatives in solution.
AB  - The UV-Vis spectra of series of polymethylmethacrylate (PMMA) copolymers with
      attached trans-azobenzene derivatives were measured in 1,1,2-trichloroethane. In
      order to gain some insight into the recorded spectra, the quantum chemical
      calculations were performed for the substituted azobenzenes using both
      configuration interaction with single excitations method (CIS) as well as density
      functional theory (DFT) with B3LYP and PBE0 functionals. The calculations were
      performed in solvent. In particular, we found that the PBE0 excitation energies
      are in very good agreement with the experimental data.

PMID- 17437137
TI  - Rational proteomics of PKD1. I. Modeling the three dimensional structure and
      ligand specificity of the C_lectin binding domain of Polycystin-1.
AB  - Polycystin-1 (Pc-1) is the 4303 amino acid multi-domain glycoprotein product of
      the polycystic kidney disease-1 (PKD1) gene. Mutations in this gene are
      implicated in 85% of cases of human autosomal dominant polycystic disease.
      Although the biochemistry of Pc-1 has been extensively studied its three
      dimensional structure has yet to be determined. We are combining bioinformatics,
      computational and biochemical data to model the 3D structure and function of
      individual domains of Pc-1. A three dimensional model of the C-type lectin domain
      (CLD) of Pc-1 (sequence region 405-534) complexed with galactose (Gal) and a
      calcium ion (Ca(+2)) has been developed (the coordinates are available on
      request, e-mail: pletnev@hwi.buffalo.edu). The model has alpha/beta structural
      organization. It is composed of eight beta strands and three alpha helices, and
      includes three disulfide bridges. It is consistent with the observed Ca(+2)
      dependence of sugar binding to CLD and identifies the amino acid side chains
      (E499, H501, E506, N518, T519 and D520) that are likely to bind the ligand. The
      model provides a reliable basis upon which to map functionally important residues
      using mutagenic experiments and to refine our knowledge about a preferred sugar
      ligand and the functional role of the CLD in polycystin-1.

PMID- 17437139
TI  - Octopuses (Octopus bimaculoides) and cuttlefishes (Sepia pharaonis, S.
      officinalis) can conditionally discriminate.
AB  - In complex navigation using landmarks, an animal must discriminate between
      potential cues and show context (condition) sensitivity. Such conditional
      discrimination is considered a form of complex learning and has been associated
      primarily with vertebrates. We tested the hypothesis that octopuses and
      cuttlefish are capable of conditional discrimination. Subjects were trained in
      two maze configurations (the conditions) in which they were required to select
      one of two particular escape routes within each maze (the discrimination).
      Conditional discrimination could be demonstrated by selecting the correct escape
      route in each maze. Six of ten mud-flat octopuses (Octopus bimaculoides), 6 of 13
      pharaoh cuttlefish (Sepia pharaonis), and one of four common cuttlefish (S.
      officinalis) demonstrated conditional discrimination by successfully solving both
      mazes. These experiments demonstrate that cephalopods are capable of conditional
      discrimination and extend the limits of invertebrate complex learning.

PMID- 17437140
TI  - Memories and anticipations control responding by rats (Rattus norvegicus) in a
      Pavlovian procedure.
AB  - In Experiment 1 each rat received two different fixed series of three trials
      each. The unconditioned stimulus occurred on Trial 1 of one series and on Trial 3
      of the other series, all other trials being nonreinforced. Previous Pavlovian
      investigations have shown that rats can remember the immediately prior reward
      outcome and anticipate the immediately subsequent reward outcome. Experiment 1
      demonstrated that rats could remember and anticipate even more remote reward
      outcomes. In Experiment 2 two groups received a series of two nonrewarded trials
      followed by a rewarded trial. It was demonstrated that a change in the
      conditioned stimulus (CS) from Trial 2 to Trial 3, which occurred in one group,
      produced weaker responding than in the other group that did not experience such
      CS change. On the basis of these findings it was suggested that the rats
      organized the trials of a series into a unit or chunk. This was concluded for two
      reasons. First, remembering and anticipating remote reward outcomes strongly
      suggests that responding is being controlled by events extending beyond the
      current trial. Secondly, the experimental manipulations employed in the Pavlovian
      situation here are similar to those used in prior human learning and animal
      instrumental learning investigations concerned with chunking. Thus, it would
      appear that chunking is a ubiquitous phenomenon appearing in human serial
      learning (e.g., Bower and Winzenz 1969; Crowder 1976), in animal instrumental
      learning (e.g., Capaldi 1992; Hulse and Dorsky 1977; Terrace 1987), and now in
      Pavlovian learning.

PMID- 17437141
TI  - Do orangutans (Pongo pygmaeus) know when they do not remember?
AB  - Metacognition refers to the ability to monitor and control one's own cognitive
      activities such as memory. Although recent studies have raised an interesting
      possibility that some species of nonhuman animals might possess such skills,
      subjects often required a numerous number of training trials to acquire the
      effective use of metacognitive responses. Here, five orangutans (Pongo pygmaeus)
      were tested whether they were able to escape spatial memory tests when they did
      not remember the location of preferred reward in a relatively small number of
      trials. The apes were presented with two identical cups, under one of which the
      experimenter hid a preferred reward (e.g., two grapes). The subjects were then
      presented with a third container, "escape response", with which they could
      receive a less preferred but secure reward (e.g., one grape). The orangutans as a
      group significantly more likely selected the escape response when the baiting of
      the preferred reward was invisible (as compared to when it was visible) and when
      the hiding locations of the preferred reward were switched (as compared to when
      they remained unchanged). Even when the escape response was presented before the
      final presentation of the memory test, one orangutan successfully avoided the
      test in which she would likely err. These findings indicate that some orangutans
      appear to tell when they do not remember correct answers in memory tests.

PMID- 17437142
TI  - Nearly automated analysis of coronary Doppler flow velocity from transthoracic
      ultrasound images: validation with manual tracings.
AB  - Coronary flow velocity reserve is obtained by manual tracings of transthoracic
      coronary Doppler flow velocity profiles as the ratio of stress versus baseline
      diastolic peak velocities. This approach introduces subjectivity in the
      measurements and limits the information which could be exploited from the Doppler
      velocity profile. Accordingly, our goals were to develop a technique for nearly
      automated detection of Doppler coronary flow velocity profile, and automatically
      compute both conventional and additional amplitude, derivative and temporal
      parameters, and validate it with manual tracings. A total of 100 patients (17
      normals, 15 patients with severe coronary stenosis, 41 with connective tissue
      disease and 27 with diabetes mellitus) were studied. Linear correlation and Bland
      Altman analyses showed that the proposed method was highly accurate and
      repeatable compared to the manual measurements. Comparison between groups
      evidenced significant differences in some of the automated parameters, thus
      representing potentially additional indices useful for the noninvasive diagnosis
      of microcirculatory or coronary artery disease.

PMID- 17437143
TI  - Macadamia nut consumption modulates favourably risk factors for coronary artery
      disease in hypercholesterolemic subjects.
AB  - Macadamia nuts are rich source of monounsaturated fats (oleic and palmitoleic
      acids) and contain polyphenol compounds, therefore, their consumption can be
      expected to impart health benefits to humans. This study was conducted to examine
      the effects of consuming macadamia nuts in hypercholesterolemic male individuals
      on plasma biomarkers of oxidative stress, coagulation and inflammation. Seventeen
      hypercholesterolemic male subjects were given macadamia nuts (40-90 g/day),
      equivalent to 15% energy intake, for a period of 4 weeks. As expected,
      monounsaturated fatty acids (16:1n-7, 18:1n-9 and 20:1n-9) were elevated in the
      plasma lipids of all volunteers following intervention with macadamia nuts.
      Plasma markers of inflammation (leukotriene, LTB(4)) and oxidative stress (8
      isoprostane) were significantly lower (1,353 +/- 225 vs. 1,030 +/- 129 pg/mL and
      876 +/- 97 vs. 679 +/- 116 pg/mL, respectively) within 4 weeks following
      macadamia nut intervention. There was a non-significant (23.6%) reduction in the
      plasma TXB(2)/PGI(2) ratio following macadamia nut consumption. This study
      demonstrates, for the first time, that short-term macadamia nut consumption
      modifies favourably the biomarkers of oxidative stress, thrombosis and
      inflammation, the risk factors for coronary artery disease, despite an increase
      in dietary fat intake. These data, combined with our previous results on
      cholesterol-lowering effects of macadamia nuts, suggest that regular consumption
      of macadamia nuts may play a role in the prevention of coronary artery disease.

PMID- 17437144
TI  - Interpersonal skill in medicine: the essential partner of verbal communication.
AB  - Medical educators have promoted skillful communication as a means for doctors to
      develop positive relationships with their patients. In practice, communication
      tends to be defined primarily as what doctors say, with less attention to how,
      when, and to whom they say it. These latter elements of communication, which
      often carry the emotional content of the discourse, are usually referred to as
      interpersonal skills. Although recognized as important by some educators,
      interpersonal skills have received much less attention than task-oriented, verbal
      aspects. Moreover, the field lacks a common language and conceptualization for
      discussing them. This paper offers a framework for describing interpersonal
      skills and understanding their relationship to verbal communication and describes
      an interpersonal skill-set comprised of Understanding, Empathy, and Relational
      Versatility.

PMID- 17437145
TI  - Dielectric properties of the plasma membrane of cultured murine fibroblasts
      treated with a nonterpenoid extract of Azadirachta indica seeds.
AB  - Neem oil is a natural product obtained from the seeds of the tree Azadirachta
      indica. In this report, we investigate the alterations of the biophysical
      properties of the plasma membrane caused by treatment with the nonterpenoid
      fraction of neem oil that we defined as methanolic extract (MEX). The dose
      response effect was evaluated and a MEX-dependent cytoxicity evidenced. The
      effect of MEX on the plasma membrane was studied by a well-established dielectric
      spectroscopy technique: electrorotation, which allows single-cell analysis. Our
      results show a structural/functional alteration of the plasma membrane with an
      evident increase of specific capacitance and conductance. The biological
      implications of this effect are discussed.

PMID- 17437146
TI  - Extracellular interaction between hCD98 and the PDZ class II domain of hCASK in
      intestinal epithelia.
AB  - The extracellular domain of the glycoprotein-associated integrin hCD98 protrudes
      into the basolateral extracellular space of the intestine and contains a PDZ
      class II-binding domain (GLLLRFPYAA, amino acids 520-529). Protein-protein
      interaction studies in vitro as well as in human colonic sections and Caco2-BBE
      cells have revealed that hCD98 coimmunoprecipitated with the basolateral membrane
      associated guanylate kinase hCASK and that this interaction occurred in a PDZ
      domain-dependent manner. These novel results, which provide the first evidence
      for a PDZ domain-dependent interaction between a membrane protein and an
      extracellular protein, open a new field of investigation related to extracellular
      signaling in cell biology.

PMID- 17437147
TI  - Evidence for vertical inheritance and loss of the leukotoxin operon in genus
      Mannheimia.
AB  - The Mannheimia subclades belong to the same bacterial genus but have taken
      divergent paths toward their distinct lifestyles. M. haemolytica + M. glucosida
      are potential pathogens of the respiratory tract in the mammalian suborder
      Ruminantia, whereas M. ruminalis, the supposed sister group, lives as a commensal
      in the ovine rumen. We have tested the hypothesis that horizontal gene transfer
      of the leukotoxin operon has catalyzed pathogenic adaptation and speciation of M.
      haemolytica + M. glucosida, or other major subclades, by using a strategy that
      combines compositional and phylogenetic methods. We show that it has been
      vertically inherited from the last common ancestor of the diverging Mannheimia
      subclades, although several strains belonging to M. ruminalis have lost the
      operon. Our analyses support that divergence within M. ruminalis following
      colonization of the ovine rumen was very rapid and that functional decay of most
      of the leukotoxin operons occurred early when the adaptation to the rumen was
      fastest, suggesting that antagonistic pleiotropy was the main contributor to
      losses in the radiating lineages of M. ruminalis. To sum up, the scenario derived
      from these analyses reflects two aspects. On one hand, it opposes the hypothesis
      of horizontal gene transfer as a catalyst of pathogenic adaptation and
      speciation. On the other hand, it indicates that losses of the leukotoxin operons
      in the radiating lineages of M. ruminalis have catalyzed their adaptation to a
      commensal environment and reproductive isolation (speciation).

PMID- 17437148
TI  - Novel group I introns encoding a putative homing endonuclease in the
      mitochondrial cox1 gene of Scleractinian corals.
AB  - Analyses of mitochondrial sequences revealed the existence of a group I intron in
      the cytochrome oxidase subunit 1 (cox1) gene in 13 of 41 genera (20 out of 73
      species) of corals conventionally assigned to the suborder Faviina. With one
      exception, phylogenies of the coral cox1 gene and its intron were concordant,
      suggesting at most two insertions and many subsequent losses. The coral introns
      were inferred to encode a putative homing endonuclease with a LAGLI-DADG motif as
      reported for the cox1 group I intron in the sea anemone Metridium senile.
      However, the coral and sea anemone cox1 group I introns differed in several
      aspects, such as the intron insertion site and sequence length. The coral cox1
      introns most closely resemble the mitochondrial cox1 group I introns of a sponge
      species, which also has the same insertion site. The coral introns are also more
      similar to the introns of several fungal species than to that of the sea anemone
      (although the insertion site differs in the fungi). This suggests either a
      horizontal transfer between a sponge and a coral or independent transfers from a
      similar fungal donor (perhaps one with an identical insertion site that has not
      yet been discovered). The common occurrence of this intron in corals strengthens
      the evidence for an elevated abundance of group I introns in the mitochondria of
      anthozoans.

PMID- 17437149
TI  - A stochastic model of nonenzymatic nucleic acid replication: "elongators"
      sequester replicators.
AB  - The origin of nucleic acid template replication is a major unsolved problem in
      science. A novel stochastic model of nucleic acid chemistry was developed to
      allow rapid prototyping of chemical experiments designed to discover sufficient
      conditions for template replication. Experiments using the model brought to
      attention a robust property of nucleic acid template populations, the tendency
      for elongation to outcompete replication. Externally imposed denaturation
      renaturation cycles did not reverse this tendency. For example, it has been
      proposed that fast tidal cycling could establish a TCR (tidal chain reaction)
      analogous to a PCR (polymerase chain reaction) acting on nucleic acid polymers,
      allowing their self-replication. However, elongating side-reactions that would
      have been prevented by the polymerase in the PCR still occurred in the simulation
      of the TCR. The same finding was found with temperature and monomer cycles. We
      propose that if cycling reactors are to allow template replication,
      oligonucleotide phenotypes that are capable of favorably altering the flux ratio
      between replication and elongation, for example, by facilitating sequence
      specific cleavage within templates, are necessary; accordingly the minimal
      replicase ribozyme may have possessed restriction functionality.

PMID- 17437150
TI  - Hemolytic anemia secondary to modified blalock-taussig shunt.
AB  - The Norwood procedure with a modified Blalock-Taussig shunt (MBTS) is the first
      of the three-stage surgical palliation for infants with hypoplastic left heart
      syndrome. We report a patient with schistocytic hemolytic anemia that developed
      following a right MBTS with a Gore-Tex graft. Hemolysis associated with a MBTS
      has not been previously reported in the literature. Multiple packed red blood
      cell transfusions were required due to desaturation and hypoxemia. Hemi-Fontan
      procedure was performed early for chronic anemia. Hemolysis resolved post
      operatively even though the patient subsequently required a Gore-Tex central
      shunt for persistent cyanosis.

PMID- 17437151
TI  - Bipedicle orbicularis oculi flap in the reconstruction of the lower eyelid
      ectropion.
AB  - BACKGROUND: Lower eyelid ectropion is conventionally reconstructed with a local
      flap or full-thickness skin graft. However, scar contracture and recurrence of
      ectropion often occur. This article describes an effective surgical technique for
      lower eyelid ectropion repair using a bipedicle orbicularis oculi muscle or
      myocutaneous flap from the upper eyelid. METHODS: This study prospectively
      analyzed collected data on the bipedicle orbicularis oculi muscle or myocutaneous
      flap from the upper eyelid in reconstruction of lower eyelid ectropion between
      1995 and 2004. The flap was used in 12 eyelid procedures for the correction of
      lower eyelid ectropion, in 10 cases with traumatic ectropion, and in 1 case with
      bilateral congenital ectropion. In these cases, a strip of orbicularis oculi
      muscle or a myocutaneous flap from the upper eyelid with two pedicles attached in
      the medial and lateral canthus was advanced to the lower eyelid to suspend the
      eyelid and repair the skin defect. RESULTS: No problem of flap viability was
      encountered in any of the patients, and all healed well. Deformities were
      corrected, and evaluation showed satisfactory function and appearance during 0.5
      to 6 years (average, 2 years) of follow-up evaluation. Eyelid malposition and
      bulkiness of the lower eyelid occurred in the early stages, but disappeared
      gradually about 3 months after the operation. There was no flap contraction,
      recurrent deformity, or significant donor site morbidity in the follow-up period.
      The incision scars were almost invisible. CONCLUSIONS: The application of
      bipedicle orbicularis oculi muscle or a myocutaneous flap from the upper eyelid
      in reconstruction of lower eyelid ectropion is effective and reduces
      postoperative morbidity.

PMID- 17437152
TI  - Magnesium sulphate as an adjuvant to total intravenous anesthesia in
      septorhinoplasty: a randomized controlled study.
AB  - BACKGROUND: The current study was designed to assess the effect of magnesium
      sulphate infusion on hemodynamic parameters, neuromuscular blocking, propofol
      consumption, serum concentration of magnesium ions, and recovery from anesthesia
      during total intravenous anesthesia. METHODS: For this study, 60 patients
      undergoing septorhinoplasty operations were randomly allocated to receive
      magnesium sulphate (group M) or saline (group C) intravenously. The patients in
      group M received 15% magnesium sulphate 50 mg/kg in 100 ml of saline, and those
      in group C received an equal volume of saline before induction of anesthesia
      followed by 8 mg/kg/h infusion of either magnesium sulphate (group M) or an equal
      volume of saline (group C) until the end of surgery. Anesthesia was induced and
      maintained with propofol, remifentanil infusions, and vecuronium in both groups.
      RESULTS: Propofol requirements were significantly lower in group M than in group
      C (p < 0.05). The hemodynamic variables were similar in the two groups. The
      neuromuscular potency of vecuronium was greater in group M than in group C (p <
      0.05). The verbal numeric scale values for pain were found to be significantly
      lower in group M than in group C (p < 0.05). Whereas the serum magnesium was in
      the normal range at the induction of anesthesia in the both groups, it was
      significantly lower in group C than in group M postoperatively (p < 0.05).
      CONCLUSION: Magnesium sulphate can be used safely as an adjuvant to total
      intravenous anesthesia for day case surgeries, with the effect from
      potentialization of neuromuscular blockade taken into consideration.

PMID- 17437153
TI  - Determination of normal calf and ankle values among medical students.
AB  - The current study was undertaken to determine the mean values of surface
      measurements from right and left calves and ankles. These measurements were taken
      from 150 second-year medical students (75 women and 75 men, ages 18 to 23 years)
      from Cukurova University in Turkey using a flexible standard measuring tape. The
      mean values for calf circumference, length of the medial head of the
      gastrocnemius muscle, distance between the inferior border of the medial head of
      the gastrocnemius muscle and the medial malleolus of tibia, and ankle
      circumference were analyzed. The observations presented in the report have
      defined anatomic parameters that need to be taken into consideration when
      cosmetic surgical procedures are performed in the calf and ankle area for this
      population.

PMID- 17437154
TI  - The "golden thread lift": radiologic findings.
AB  - A 48-year-old patient reported pain in her face and neck. Within 10 years she had
      undergone three "golden thread lift" suspension procedures, the last one 2 years
      previously. Skull radiographs showed complete fragmentation of all the implants
      into small pieces, and a total loss of their vector orientation.

PMID- 17437155
TI  - A surgical algorithm using open rhinoplasty for correction of traumatic twisted
      nose.
AB  - In this series, the authors present their experience with correction of the
      traumatic twisted nose in Asians using open rhinoplasty. A standard surgical
      algorithm was followed to determine treatment strategies for 92 patients with
      traumatic twisted nose at the Tri-Service General Hospital in Taiwan between 1
      August 2001 and 1 June 2004. A retrospective chart review was performed to
      collect patient data and surgical details. A follow-up self-evaluation survey
      regarding satisfaction with nasal function and aesthetics was distributed to all
      the participants. All the patients underwent open rhinoplasties under general
      anesthesia. The 87 males and 5 females were 15 to 53 years of age (mean, 28
      years). Their postoperative periods were uneventful and without complications.
      Patient self-evaluations were largely positive, reporting improvement in nasal
      function. The authors propose a simple surgical algorithm using open rhinoplasty
      for optimal correction of traumatic twisted nose deformities. The algorithm,
      which is adaptable to a variety of anatomic deformities, guides surgical decision
      making that yields consistently satisfactory functional and aesthetic results.

PMID- 17437156
TI  - Study of efficacy of bilayer mesh device versus conventional polypropelene hernia
      system in inguinal hernia repair: early results.
AB  - BACKGROUND: The Prolene hernia system (PHS) is a three-dimensional mesh device
      that combines three approaches to hernia repair, but its high cost precludes its
      widespread use in developing countries. We describe our experience with an
      indigenous bilayer mesh device that works on a similar principle, and compare its
      efficacy with conventional PHS. MATERIALS AND METHODS: A total of 84 patients
      with unilateral/bilateral primary uncomplicated inguinal hernia were recruited
      for the study over a 1-year period and randomized into two groups. Group 1, which
      consisted of 40 patients, received the indigenous device, and group 2, 44
      patients, received conventional PHS. Mean operative time and the patients' visual
      assessment scores (VAS) for pain were primary outcome measures. Patient were
      reviewed in out patients department at intervals of 3 months, and the incidence
      of complications and recurrence was noted. This was the secondary outcome
      measure. RESULTS: The two group were comparable in terms of age, type of hernia,
      and mean duration of follow-up. The mean operative time was 32.1 min (+/- 5.5)
      and 33.25 (+/- 5.3) in groups 1 and 2, respectively, and the mean VAS score was
      2.25 and 2.27 in the respective groups. There was no statistically significant
      difference. Similarly, the was no significant difference in incidence of
      complications noted between the two groups (3/40 versus 4/44, respectively).
      There were no recurrences noted during the period of observation. CONCLUSIONS:
      The indigenous bilayer device described in this study combines the advantages of
      two well-publicized techniques of hernia repair: inlay repair and onlay repair.
      It offers the benefits of conventional PHS repair but is far less expensive and
      is quite suitable for routine use in centers like ours in a developing nation,
      where financial resources are a constraint.

PMID- 17437157
TI  - Attenuation of Kupffer cell function in acute on chronic liver injury enhanced
      engraftment of transplanted hepatocytes.
AB  - BACKGROUND: The present study was designed to elucidate the relationship of
      engraftment efficiency of transplanted cells and Kupffer cell function in mice
      with acute on chronic liver injury and acute liver injury. METHODS: The recipient
      dipeptidyl peptidase IV knockout (DPPIV(-/-)) mice were divided into two groups:
      (1) the acute on chronic liver injury group (CCl(4)/APAP group) that received
      CCl(4) (1 ml/kg) twice a week for 4 weeks following one dose of acetaminophen
      (APAP), 600 mg/kg; (2) the acute liver injury group (APAP-only group) that
      received a single dose of APAP at 600 mg/kg. DPPIV(+/+) hepatocytes were
      transplanted 24 h after APAP intoxication. Engraftment efficiency was evaluated
      at day 7 and day 14 after transplantation. The tumor necrosis factor-alpha (TNF
      alpha) mRNA expression level of Kupffer cells immediately before cell
      transplantation was compared between the two groups before and after
      lipopolysaccharide (LPS, 100 ng/ml) stimulation. RESULTS: The number of
      transplanted cells and clusters in each 100x microscopic field were higher in the
      CCl(4)/APAP group at both day 7 (21.5 +/- 6.3 versus 8.3 +/- 4.0, p < 0.001; 14.9
      +/- 4.6 versus 6.6 +/- 3.4, p < 0.001, respectively) and day 14 (17.3 +/- 4.4
      versus 10.2 +/- 3.3, p = 0.001; 12.6 +/- 3.2 versus 7.9 +/- 1.6, p = 0.004,
      respectively). After LPS stimulation, the expression level of TNF-alpha was lower
      (175.7 +/- 54.6 versus 465.6 +/- 64.2, p = 0.002), and the increment of TNF-alpha
      expression was also less significant in the CCl(4)/APAP group (1.5-fold versus
      6.5-fold, p = 0.014). CONCLUSIONS: Chronic liver injury desensitized Kupffer
      cells and reduced TNF-alpha expression, two results that correlated with the
      increased engraftment of transplanted cells.

PMID- 17437158
TI  - Angioplasty for non-arteriosclerotic renal artery stenosis: the efficacy of
      cutting balloon angioplasty versus conventional angioplasty.
AB  - PURPOSE: We examined the efficacy of conventional balloon angioplasty and cutting
      balloon angioplasty (CBA) for the treatment of non-arteriosclerotic renal artery
      stenosis (RAS). MATERIALS AND METHODS: From 1993 to 2005, 20 patients underwent
      27 percutaneous transluminal renalangioplasty (PTRA) for non-arteriosclerotic RAS
      (men: 8, women: 12, 25.5 +/- 2 years old; 16 fibromuscular dysplasia (FMD), 4
      Takayasu disease). We evaluated the efficacy of CBA by comparing the rate of
      initial technical success and surgical conversion. RESULTS: Before the clinical
      authorization of CBA, three of twelve patients (25 %) underwent surgical bypass
      due to the failure of PTRA due to the hardness of the lesion. After the approval
      of cutting balloon, we performed CBA in four cases (2 FMD,2 Takayasu disease) to
      dilate hard lesions, within which a properly sized balloon could not dilate due
      to their hardness, or to reduce the risk of local dissection. Initial successes
      were obtained in all patients (8/8, 100%) and none of the patients underwent
      surgical conversion. Despite of the good initial result, restenosis was observed
      in three cases within 6 month (3/4, 75%). Additional interventions were performed
      in all patients, then, the severity of the restenotic lesion was found not to be
      exceeded comparing with the initial lesion. CONCLUSION: The cutting balloon
      angioplasty may be safe and useful procedure for hard lesions of RAS caused by
      non-arteriosclerotic disease? especially fibromuscular dysplasia. The cutting
      balloon may provide the initial success, but the effect on long-term patency is
      still controversial.

PMID- 17437159
TI  - Risks of oral sodium phosphate for pre-colonoscopy bowel preparation in children:
      response to Drs. Hassall and Lobe.

PMID- 17437160
TI  - A novel mutation in the LRP5 gene is associated with osteoporosis-pseudoglioma
      syndrome.

PMID- 17437161
TI  - A relationship between pharmacokinetics (PK) and the efficacy of infliximab for
      patients with rheumatoid arthritis: characterization of infliximab-resistant
      cases and PK-based modified therapy.
AB  - Infliximab, a chimeric anti-tumor necrosis factor alpha (TNF-alpha) monoclonal
      antibody, has been recognized as significantly improving the course of rheumatoid
      arthritis (RA); however, a subset of patients shows poor responses. To understand
      the mechanism underlying such unresponsiveness, I examined the clinical
      pharmacokinetics (PK) of infliximab, using time-serum concentration profiles
      obtained from 21 RA patients who had received infliximab therapy in combination
      with methotrexate (MTX). At week 14 of therapy, 15 cases achieved good or
      moderate responses in the European League Against Rheumatism (EULAR) criteria,
      and 3 cases resulted in nonresponders. The others discontinued therapy because of
      severe adverse effects or aggravation of disease activities. The means of
      distribution volume and elimination half-life (t (1/2)) during the first 2 weeks
      were 0.05 l/kg and 9.5 days, respectively. Through 14 weeks, most good and
      moderate responders maintained serum concentrations of more than 1 microg/ml,
      even immediately before the next infusions. Only 3 cases among good or moderate
      responders showed undetectable levels of trough serum concentration at week 14.
      In contrast, the PK profiles of all nonresponders except one showed rapid
      clearance during therapy. These data support the idea that the rapid clearance of
      infliximab is the main cause of poor therapeutic responses. I also found that the
      t (1/2) during the first 2 weeks is inversely correlated to the disease activity
      scores for 28 joints at the start of treatment, suggesting that TNF-alpha levels
      may determine the disease activity of RA. For patients who showed a rapid
      clearance of infliximab, the increased use of prednisone or MTX was beneficial to
      achieve sufficient clinical responses. The addition of tacrolimus was effective
      to improve the clinical outcomes of nonresponders. Thus PK data apparently offer
      guidance when modified treatment for infliximab-resistant RA patients is being
      considered.

PMID- 17437162
TI  - Prospective study of low-dose cyclosporine A in patients with refractory lupus
      nephritis.
AB  - We evaluated the efficacy and safety of low-dose cyclosporine A (CsA) in patients
      with refractory lupus nephritis. Nine patients with systemic lupus erythematosus
      who had lupus nephritis resistant to previous treatment with glucocorticoids and
      immunosuppressants other than CsA were enrolled in a prospective, open-label
      study. All patients initially received 2.5 mg/kg per day of CsA; the dosage was
      adjusted to reach a blood trough level of 80-150 ng/ml. The urinary protein
      concentration decreased significantly 2 weeks after the initiation of treatment.
      After 30 weeks of CsA treatment, the mean urinary protein concentration was more
      than 50% lower than the baseline value, and urinary casts had decreased
      significantly. There were no significant changes in the levels of serum
      creatinine, serum anti-double-stranded DNA antibodies, or CH50 during any part of
      the study. The dose of glucocorticoids was significantly tapered by approximately
      50%, without any disease flare. Hypertension developed in one patient, but was
      controlled with antihypertensive agents. Our results suggest that low-dose CsA
      therapy is an effective and less toxic alternative to conventional
      cyclophosphamide therapy for the management of refractory lupus nephritis.

PMID- 17437164
TI  - Long-term results of open elbow synovectomy for rheumatoid arthritis.
AB  - Long-term results of open synovectomy of the elbow with rheumatoid arthritis (RA)
      were reviewed in 15 elbows. The subjects were evaluated at two time points with
      average follow-up periods of 4 and 8.7 years, and the results were compared
      between the two follow-ups. The Mayo Clinic performance score showed significant
      improvement in pain, motion, and daily function from the intermediate to the long
      term follow-up. Overall results were satisfactory with little time-dependent
      deterioration in radiological grading, confirming the long-term effectiveness of
      this procedure.

PMID- 17437163
TI  - Influence of methotrexate dose on its efficacy and safety in rheumatoid arthritis
      patients: evidence based on the variety of prescribing approaches among
      practicing Japanese rheumatologists in a single institute-based large
      observational cohort (IORRA).
AB  - The optimal methotrexate dose differs between rheumatoid arthritis (RA) patients,
      and dose-escalation strategies also differ among rheumatologists. By taking
      advantage of the heterogeneous methotrexate dosing that occurs among Japanese
      rheumatologists, we analyzed the efficacy and safety of different methotrexate
      doses. A large observational cohort of RA patients, IORRA, was established in
      2000. A dataset from April 2003 that included 4578 RA patients was used for a
      cross-sectional analysis, while a dataset of 1649 patients who received
      methotrexate from October 2000 to October 2005 was used for a longitudinal
      analysis. The cross-sectional analysis included 12 rheumatologists who prescribed
      methotrexate to more than 60 patients. Mean methotrexate dose ranged widely (4.8
      9.0 mg/week) among rheumatologists with a significant positive relationship
      between average methotrexate dose and the percentage of patients with Disease
      Activity in 28 Joints (DAS28) scores below 3.2. During the longitudinal analysis,
      both methotrexate prescription frequency and the average dose prescribed by 16
      rheumatologists increased. Overall disease activity as assessed by DAS28-area
      under the curve (AUC) and disability progression as assessed by Japanese version
      of the Health Assessment Questionnaire (JHAQ)-slope inversely correlated with the
      extent of methotrexate use. This study demonstrated that extensive methotrexate
      use effectively suppressed RA disease activity and inhibits disability
      progression. In addition, we have found that it is critical to pay attention to
      patient-reported adverse reactions.

PMID- 17437165
TI  - Replacement of the first metatarsophalangeal joint with a Swanson implant
      accompanied by open-wedge osteotomy of the first metatarsal bone for hallux
      valgus in rheumatoid arthritis.
AB  - Hallux valgus is very common in rheumatoid arthritis (RA) and mostly accompanied
      by varus deformity of the first metatarsal bone, which is often corrected in
      surgeries for hallux valgus in nonarthritic condition, but rarely in RA. We
      performed the replacement of the first metatarsophalangeal (MTP) joint with a
      Swanson hinge toe implant accompanied with open-wedge osteotomy of the first
      metatarsal bone, aiming at reconstruction of a functioning first MTP joint
      without recurrence of hallux valgus. Fifteen feet of 11 patients with RA were
      studied with a mean follow-up period of 45.1 months. The American Orthopaedic
      Foot and Ankle Society (AOFAS) scale improved significantly from 39 points
      preoperatively to 81.7 at the last follow-up. The hallux valgus angle (HVA),
      angle between the first and second metatarsal bones (M1/2), and that between the
      first and fifth (M1/5), measured on standing anteroposterior radiographs,
      decreased significantly from 49.8 degrees, 16.7 degrees, and 34.4 degrees
      preoperatively to 10.9 degrees, 8.7 degrees, and 22.2 degrees at the last follow
      up, respectively. Union of the corrected first metatarsal bone was recognized in
      all cases and no such problems as infection, dislocation, or implant fracture
      were observed. These data suggest that replacement of the first MTP joint with a
      Swanson implant accompanied with open-wedge osteotomy of the first metatarsal
      bone can be a useful option for hallux valgus in RA.

PMID- 17437166
TI  - Celecoxib prevents juxta-articular osteopenia and growth plate destruction
      adjacent to inflamed joints in rats with collagen-induced arthritis.
AB  - The effect of celecoxib, a selective cyclooxygenase-2 inhibitor, on juxta
      articular osteopenia and growth plate destruction adjacent to inflamed joints was
      investigated in rats with collagen-induced arthritis. Forty rats were assigned to
      the following six groups: (1) an untreated arthritis group; (2-5) arthritis rats
      receiving indomethacin (3 mg/kg per day), dexamethasone (0.2 mg/kg per day), or
      celecoxib (5 or 50 mg/kg per day), and (6) normal control rats. Drugs were
      administered for 2 weeks from the onset of arthritis. Then the hind paws were
      measured. Juxta-articular osteopenia and growth plate destruction adjacent to
      inflamed joints were also assessed using plain radiography, bone mineral density
      measurement, histology, and histomorphometry. Each treatment reduced
      inflammation, but only dexamethasone and high-dose celecoxib prevented bone loss
      adjacent to inflamed joints and significantly decreased bone resorption. In
      contrast, no treatment affected bone formation parameters. Growth plate
      destruction adjacent to inflamed joints was prevented by indomethacin,
      dexamethasone, and high-dose celecoxib. Although dexamethasone abolished
      inflammation, growth plate destruction was still observed. In conclusion, among
      the various drugs tested, only celecoxib had a preventive effect on both growth
      plate destruction and bone loss adjacent to inflamed joints in this arthritis
      model.

PMID- 17437167
TI  - Step-up versus primary intensive approach to the treatment of interstitial
      pneumonia associated with dermatomyositis/polymyositis: a retrospective study.
AB  - Corticosteroids (CS) are the standard initial treatment for interstitial
      pneumonia (IP) associated with dermatomyositis (DM)/polymyositis (PM). However,
      many patients fail to respond and have significantly high mortality even if
      immunosuppressive drugs (ISDs) are subsequently added, while a more intensive
      initial approach using ISDs is suggested to improve their survival. We conducted
      a retrospective study to examine the association between initial therapeutic
      approaches and clinical outcomes of active IP in DM/PM patients. We reviewed
      medical records of 34 consecutive DM/PM patients who had active IP defined by the
      presence of pulmonary function abnormality or active symptoms, and compared
      clinical outcome between those patients to whom ISDs were added if CS alone did
      not result in a favorable response (a step-up approach) and those who were
      started on ISDs simultaneously with CS (a primary intensive approach). Clinical
      endpoints were death, pulmonary death, and progression or improvement of
      pulmonary function. The step-up approach was used in 20 patients, to 11 of whom
      ISDs were eventually added after a median of 2.0 weeks, while the primary
      intensive approach was used in 14 patients. The primary intensive approach group
      had significantly better survival than the step-up approach group (P = 0.030 by
      the log-rank test). These two groups did not differ significantly in demographic
      characteristics and baseline clinical and laboratory features. Intensive approach
      by starting ISDs simultaneously with CS in the initial treatment for active IP in
      DM/PM patients was associated with better survival, emphasizing the impact of
      initial treatment on their survival. Prospective clinical investigation of this
      approach is now needed, but the limited clinical utility of CS as an initial
      treatment might ethically challenge clinical-trial designing.

PMID- 17437168
TI  - Intermittent intravenous cyclophosphamide pulse therapy for the treatment of
      active interstitial lung disease associated with collagen vascular diseases.
AB  - The availability of intravenous cyclophosphamide (CYC) pulse therapy for collagen
      vascular diseases (CVD)-associated interstitial lung disease (ILD) has been
      indicated. However, the standard protocol concerning the dosage and the interval
      of CYC infusion has not yet been established. The aim of this study is to
      elucidate the efficacy and the safety of our "divided administration" protocol of
      CYC for the treatment of CVD-ILD. The treatment protocol consists of two steps:
      step 1, CYC 400-500 mg at 10-day intervals for at least 30 days, and step 2, CYC
      500 mg at 14-day intervals for at least 4 weeks. The ILD activities were
      monitored by respiratory symptoms, serum levels of KL-6 (a serological marker of
      IP), chest computed tomography (CT), and pulmonary function tests. Seventeen
      patients [nonspecific interstitial pneumonia (NSIP), 12 patients; usual
      interstitial pneumonia (UIP), 4; lymphocytic interstitial pneumonia (LIP), 1]
      accomplished the study protocol. The sessions of CYC infusion ranged from 5 to 20
      (mean, 8.3). In all patients, respiratory symptoms were improved and the serum
      levels of KL-6 were decreased (from 1572 +/- 904 to 978 +/- 392 U/ml; P < 0.01).
      Chest CT findings were improved in 4 patients (23.5%): they were all classified
      as NSIP; not deteriorated, 13 patients (76.5%). An improvement in the vital
      capacity percentage (%VC) was recognized in 10 patients (78.6%) and in diffusing
      capacity of carbon monoxide (%DLco) in 8 patients (61.5%). Nevertheless, mean %VC
      and mean %DLco did not change significantly. No major adverse event(s) occurred.
      The efficacy and safety of our "divided administration" protocol of CYC for CVD
      ILD was demonstrated.

PMID- 17437169
TI  - Inositol 1,4,5-trisphosphate receptors are autoantibody target antigens in
      patients with Sjogren's syndrome and other systemic rheumatic diseases.
AB  - IP(3)R2 and IP(3)R3 double knock-out mice present with exocrine dysfunctions such
      as secretion deficits of saliva and pancreatic juice. Therefore, we investigated
      whether the presence of antibodies to IP(3)Rs could be found in patients with
      Sjogren's syndrome, and the location of the epitopes. Subjects included 35
      primary Sjogren's syndrome, 39 secondary Sjogren's syndrome, 144 rheumatoid
      arthritis, and 96 other connective tissue disease patients. As controls, 33
      healthy subjects were included. Immunoblot was conducted using recombinant
      proteins IP(3)R1, IP(3)R2, and IP(3)R3 made from full-length cDNA, and core,
      T604, and EL for epitope mapping. Antibodies to IP(3)R1 in sera from patients
      with primary Sjogren's syndrome, secondary Sjogren's syndrome, and rheumatoid
      arthritis were found to be positive in 17 of 35 (48.6%), 13 of 39 (33%), and 34
      of 124 (27.4%) cases, respectively. These frequencies were significantly higher
      than the 1 of 33 (3.0%) found in normal healthy subjects. The frequency of anti
      IP(3)R2 antibodies in rheumatoid arthritis was found to be higher than those
      found in Sjogren's syndrome, systemic lupus erythematosus, and systemic
      sclerosis. Anti-IP(3)R2 antibodies found in rheumatoid arthritis primarily
      recognized residues 578-2171 of the internal coupling and regulatory domain. On
      the other hand, anti-IP(3)R1 found in Sjogren's syndrome recognized residues 224
      604 of the core protein IP(3)R1. Anti-IP(3)R1 antibodies were present in 48.6% of
      primary Sjogren's syndrome and in 3.0% of normal healthy subjects. Anti-IP(3)R2
      antibodies were detected most frequently in rheumatoid arthritis. Locations of
      the antigenic epitopes were found to differ among the disease conditions.

PMID- 17437170
TI  - A case of life-threatening refractory polychondritis successfully treated with
      combined intensive immunosuppressive therapy with methotrexate.
AB  - Relapsing polychondritis (RP) is a rare disease of unknown etiology causing
      systematic inflammation and resulting in destruction of cartilaginous tissues. We
      describe here an 18-year-old Japanese woman who developed severe airway stenosis
      as the initial symptom with auricular, nasal, and ocular inflammation. The effect
      of high dose oral steroid, methylprednisolone pulse therapy, and cyclophosphamide
      was temporary and her conditioning was worsening. Finally we added methotrexate
      to the immunosuppressive treatment and achieved reduction of disease activity.
      This case illustrates the potentially fatal sudden onset of airway inflammation
      that can occur with this disorder, and the effectiveness of methotrexate.

PMID- 17437171
TI  - A case of relapsing polychondritis with bilateral sensorineural hearing loss and
      perforation of the nasal septum at the onset.
AB  - A 33-year-old woman suffered from epistaxis and perforation of the nasal septum.
      Based on a biopsy of nasal mucosa, Wegener's granulomatosis was suspected
      initially. Her nasal symptoms improved spontaneously, but tinnitus, hearing loss,
      and dizziness appeared within 3 months. Laboratory analyses revealed no
      inflammation, and antineutrophil cytoplasmic antibodies were negative. Audiometry
      revealed bilateral sensorineural hearing loss. A second biopsy of the nasal
      septum showed an inflammatory change in the cartilage. Thus we diagnosed early
      stage relapsing polychondritis.

PMID- 17437172
TI  - A case of antiphospholipid antibody syndrome that manifested in the course of
      basal cell carcinoma.
AB  - A case of antiphospholipid antibody syndrome (APS) is presented, which manifested
      5 years after onset of basal cell carcinoma (BCC). There were multiple collateral
      veins due to portal vein thrombosis. Because immunological abnormalities
      including anti-cardiolipin beta(2) glycoprotein-I antibody improved after
      surgical resection of BCC, it is likely that APS had occurred as a paraneoplastic
      syndrome with BCC. This case suggests that it is necessary to investigate the
      presence of APS when BCC is complicated by some coagulopathies.

PMID- 17437173
TI  - A case of dermatomyositis complicated with pneumomediastinum.
AB  - We herein describe a 16-year-old boy with pneumomediastinum, pneumothorax, and
      subcutaneous emphysema as the initial symptoms of dermatomyositis (DM). His
      pneumomediastinum disappeared after strict bed rest and he was thereafter
      successfully treated with oral prednisolone and cyclosporine A. His condition was
      further complicated with mild interstitial lung disease, arrhythmia, and skin
      ulcers on his fingertips, right elbow, ear, and sacral region. Pneumomediastinum
      is a rare complication of DM and its pathogenesis remains unclear. We review the
      literature and discuss the possible mechanism of this disease.

PMID- 17437174
TI  - Hodgkin's lymphoma initially presenting with polymyalgic symptoms: a case report.
AB  - The association of polymyalgic symptoms and lymphoma is a rare event whose
      pathogenesis remains to be clarified. Here, we describe a case of a 75-year old
      man with Hodgkin's lymphoma, who had presented with polymyalgic symptoms
      suggesting polymyalgia rheumatica. An intensive investigation with respect to
      malignancy was initially negative. Corticosteroid treatment was administered
      first and a dramatic clinical improvement was achieved. Four months later, when
      the corticosteroid treatment was tapered off, the initial manifestations
      reappeared. After the development of lymph node enlargement, the patient was
      diagnosed by lymph node biopsy as having Hodgkin's lymphoma. The lymphadenopathy
      and musculoskeletal manifestations all responded well to chemotherapy. Hodgkin's
      lymphoma should be considered in the differential diagnosis of PMR. These
      musculoskeletal syndromes should alert the physician to possible paraneoplastic
      manifestations of an evolving neoplasm.

PMID- 17437175
TI  - Insufficiency fracture of the acetabulum without apparent trauma.
AB  - A 76-year-old woman presented history of left hip joint pain on walking, which
      occurred after she bent to move a planter. Plain radiographs showed no fracture.
      Bone scintigraphy revealed accumulation, and magnetic resonance imaging showed a
      low signal area on T1-weighted images. We diagnosed an insufficiency fracture and
      pain decreased naturally on conservative treatment. Insufficiency fracture of the
      acetabulum should be considered when elderly patients have hip joint pain.
      Magnetic resonance imaging and bone scintigraphy is most useful for the
      diagnosis.

PMID- 17437176
TI  - Successful treatment of a patient with refractory adult Still's disease by
      tacrolimus.
AB  - Adult Still's disease (ASD) is a systemic rheumatic disease characterized by high
      spiking fever, erythema, polyarthritis, and increased levels of C-reactive
      protein, ferritin, and interleukin (IL)-18. Recently, biological agents targeting
      proinflammatory cytokines such as tumor necrosis factor (TNF) alpha, IL-1, and IL
      6 have been described as effective treatments for refractory ASD. Herein, we
      present a patient with ASD, who was successfully treated by tacrolimus
      concomitant with corticosteroid, while infliximab and etanercept were not
      effective. Tacrolimus may be one of the drugs for the ASD patients refractory to
      the conventional treatments including TNF inhibitors.

PMID- 17437177
TI  - Severe subcutaneous generalized edema in a patient with dermatomyositis.
AB  - Subcutaneous generalized edema associated with dermatomyositis (DM)/polymyositis
      (PM) is extremely rare. Herein we report a case of severe subcutaneous
      generalized edema complicating DM. A 78-year-old woman was hospitalized in our
      department because of massive edema in the four limbs. Elevated muscle enzymes,
      heliotrope rash, results of electromyography, and muscle biopsy confirmed the
      diagnosis of DM. The absence of other diseases that could cause the symptoms
      indicated that massive edema was correlated with the pathophysiology of DM.
      Although myopathy and edema responded well to oral prednisolone, dysphagia
      persisted. We conclude that subcutaneous generalized edema can occur during the
      course of DM/PM, and subcutaneous vasculopathy may be involved in the
      pathogenesis of DM/PM.

PMID- 17437178
TI  - Therapeutic efficacy and safety profile of infliximab in active systemic lupus
      erythematosus.
AB  - Since levels of the proinflammatory cytokine tumor necrosis factor alpha
      (TNFalpha) are significantly increased in systemic lupus erythematosus (SLE) and
      may be involved in the disease pathogenesis, we report on the safety and efficacy
      of infliximab, a chimeric monoclonal antibody directed against TNFalpha, given to
      a patient with difficult-to-treat active nonrenal SLE. This patient, who failed
      to remit with full doses of glucocorticoids, hydroxychloroquine, methotrexate,
      and azathioprine, went into sustained remission with the addition of infliximab
      infusions. Glucocorticoids could be tapered off completely.

PMID- 17437179
TI  - Association of diabetes with mammographic breast density and breast cancer in the
      Minnesota breast cancer family study.
AB  - Data from the Minnesota Breast Cancer Family Study cohort (n=6,130 women) were
      used to examine the association of type II diabetes with mammographic percent
      density and incident breast cancer (BC). Exposures and outcomes were self
      reported. The first set of analyses evaluated diabetes (DM) as a risk factor for
      breast cancer. A total of 403 women (6.6%) reported a diagnosis of type II
      diabetes and 333 women reported an incident breast cancer. Women who reported
      type II diabetes had an age-adjusted relative risk (RR) for breast cancer of 1.44
      (95% CI 0.89-2.32) compared to those who did not. Adjustment for covariates
      strengthened the association (RR 1.61, 95% CI 0.98-2.62). Mammograms were
      retrieved on women over the age of 40 and percent density was estimated with a
      user-assisted thresholding program. Cross-sectional analyses revealed that mean
      levels of mammographic density were not statistically significantly different
      between diabetic and non-diabetic women. Results were similar within strata of
      menopausal status. Breast cancer cases with diabetes did not have a significantly
      higher percent density than cases without diabetes. Our findings suggest that
      breast cancer risk may be increased among women with type II diabetes, but that
      type II diabetes does not significantly influence mammographic breast density.

PMID- 17437180
TI  - Alcohol consumption, cigarette smoking, and endometrial cancer risk: results from
      the Netherlands Cohort Study.
AB  - OBJECTIVE: To examine the association between alcohol consumption, cigarette
      smoking, and endometrial cancer. METHODS: In 1986, the Netherlands Cohort Study
      was initiated. A self-administered questionnaire on dietary habits and other
      cancer risk factors was completed by 62,573 women. Follow-up for cancer was
      established by record linkage to the Netherlands Cancer Registry. RESULTS: After
      11.3-years of follow-up, 280 incident endometrial cancer cases were available for
      analyses. In multivariate analysis, the rate ratio (RR) for alcohol users versus
      non-users was 1.06 (95% Confidence Interval (95% CI)=0.78-1.43). There were
      neither dose-dependent trends nor associations with different types of beverages.
      The RR for former and current smokers versus never-smokers was 0.83 (95% CI=0.58
      1.20) and 0.59 (95% CI=0.40-0.88), respectively. These estimates did not change
      significantly when body mass index (BMI) and age at menopause were added to the
      models. CONCLUSIONS: There is no association between alcohol consumption and
      endometrial cancer. Current smoking is associated with a reduced risk of
      endometrial cancer. This association is neither mediated by BMI nor by age at
      menopause.

PMID- 17437181
TI  - Estimating riverine discharge of nitrogen from the South Korea by the mass
      balance approach.
AB  - The main objective of this research was to estimate the total mass of nitrogen
      discharged from various sources in Korea using the mass balance approach. Three
      different nitrogen mass balances were presented: (1) agricultural activities
      including raising crops and animal husbandry; (2) domestic activities, and (3)
      activities in forest and urban areas. These nitrogen balances were combined to
      estimate riverine discharge of nitrogen to the ocean in national scale. Nitrogen
      inputs include atmospheric deposition, biological nitrogen fixation, application
      of inorganic fertilizers/manures, animal feed/imported foodstuffs, and meat/fish.
      Nitrogen outputs include ammonia volatilization, denitrification, human/animal
      waste generation, crop/meat production, and riverine discharge to the ocean. The
      estimated total nitrogen input in Korea was 1,194.5 x 10(3) tons N/year. Nitrogen
      discharged into rivers was estimated as 408-422 x 10(3) tons N/year, of which 66
      71% was diffuse in origin. The estimated diffuse discharges for land uses were
      estimated as 82 x 10(3) tons N/year from agricultural areas, 7 x 10(3) tons
      N/year from forestry and 75 x 10(3) tons N/year from urban and industrial areas.

PMID- 17437182
TI  - Inducible expression of phospholipid transfer protein (PLTP) in transgenic mice:
      acute effects of PLTP on lipoprotein metabolism.
AB  - One main determinant in high-density lipoprotein (HDL) metabolism is phospholipid
      transfer protein (PLTP), a plasma protein that is associated with HDL. In
      transgenic mice overexpressing human PLTP we found that elevated plasma PLTP
      levels dose-dependently increased the susceptibility to diet-induced
      atherosclerosis. This could be mainly due to the fact that most functions of PLTP
      are potentially atherogenic, such as decreasing plasma HDL levels. To further
      elucidate the role of PLTP in lipoprotein metabolism and atherosclerosis we
      generated a novel transgenic mouse model that allows conditional expression of
      human PLTP. In this mouse model a human PLTP encoding sequence is controlled by a
      Tet-On system. Upon induction of PLTP expression, our mouse model showed a
      strongly increased PLTP activity (from 3.0 +/- 0.6 to 11.4 +/- 2.8 AU, p <
      0.001). The increase in PLTP activity resulted in an acute decrease in plasma
      cholesterol of 33% and a comparable decrease in phospholipids. The decrease in
      total plasma cholesterol and phospholipids was caused by a 35% decrease in HDL
      cholesterol level and a 41% decrease in HDL-phospholipid level. These results
      demonstrate the feasibility of our mouse model to induce an acute elevation of
      PLTP activity, which is easily reversible. As a direct consequence of an increase
      in PLTP activity, HDL-cholesterol and HDL-phospholipid levels strongly decrease.
      Using this mouse model, it will be possible to study the effects of acute
      elevation of PLTP activity on lipoprotein metabolism and pre-existing
      atherosclerosis.

PMID- 17437183
TI  - Reconstitution of the water-oxidizing complex in manganese-depleted photosystem
      II preparations using synthetic binuclear Mn(II) and Mn(IV) complexes: production
      of hydrogen peroxide.
AB  - Reconstitution of Mn-depleted PSII particles with synthetic binuclear Mn
      complexes (one Mn(II)(2) complex and one Mn(IV)(2) complex) was examined. In both
      cases the electron-transfer rates in the reconstituted systems were found to be
      up to 75-82% of that measured in native PSII but the oxygen evolution activity
      remained lower (<5-40%). However, hydrogen peroxide was also produced by the
      reconstituted samples. These samples therefore represent a new type of
      reconstituted PSII that generates hydrogen peroxide as the final product in
      reconstituted PSII centers.

PMID- 17437184
TI  - Group I introns and GNRA tetraloops: remnants of 'The RNA world'?
AB  - GNRA tetraloops, found in high frequency in natural RNAs, make loop-receptor
      interactions, stabilizing the tertiary structure of Group I introns, a class of
      small RNAs. Analyzing 230 Group I introns, to study the distribution and sequence
      pattern of the GNRA tetraloops, we suggest that these features reflect the
      ancestral nature of these catalytic molecules, in a prebiotic RNA world. The
      adenosine rich GNRA tetraloops would have interacted with each other through long
      range RNA-RNA interactions to form higher order structures forming potential
      sites that render the propensity for the short RNAs to bind to metal ions from
      the prebiotic pool, aiding them to act as metalloenzymes.

PMID- 17437185
TI  - Clostridium difficile toxin A-induced apoptosis is p53-independent but depends on
      glucosylation of Rho GTPases.
AB  - Clostridium difficile toxin A (TcdA) is one of two homologous
      glucosyltransferases that mono-glucosylate Rho GTPases. HT29 cells were
      challenged with wild-type and mutant TcdA to investigate the mechanism by which
      apoptosis is induced. The TcdA-induced re-organization of the actin cytoskeleton
      led to an increased number of cells within the G2/M phase. Depolymerization of
      the actin filaments with subsequent G2/M arrest, however, was not causative for
      apoptosis, as shown in a comparative study using latrunculin B. The activation of
      caspase-3, -8, and -9 strictly depended on the glucosylation of Rho GTPases.
      Apoptosis measured by flow cytometry was completely abolished by a pan-caspase
      inhibitor (z-VAD-fmk). Interestingly, cleavage of procaspase-3 and Bid was not
      inhibited by z-VAD-fmk, but was inhibited by the calpain/cathepsin inhibitor
      ALLM. Cleavage of procaspase-8 was susceptible to inhibition by z-VAD-fmk and to
      the caspase-3 inhibitor Ac-DMQD-CHO, indicating a contribution to the activation
      of caspase-3 in an amplifying manner. Although TcdA induced mitochondrial damage
      and cytochrome c release, p53 was not activated or up-regulated. A p53
      independent apoptotic effect was also checked by treatment of HCT 116 p53(-/-)
      cells. In summary, TcdA-induced apoptosis in HT29 cells depends on glucosylation
      of Rho GTPases leading to activation of cathepsins and caspase-3.

PMID- 17437187
TI  - Community-driven learning activities, creating futures: 30,000 people can't be
      wrong - can they?
AB  - A major vehicle for the practice of community psychology is through the
      organization of community-based activities. My colleagues and I have developed
      many programs for community learning centers, in-school and after school
      programs, and community technology centers. In the last 10 years, 30,000 people
      (mostly children) have participated in activities designed for enjoyment and
      learning, with a view to adding protective factors and reducing negative factors
      in at-risk communities. Development of these programs for literacy, education,
      life and work skills, has increasingly followed a community responsive model.
      Within each program, we created explicit images of future success. That is,
      people could see themselves being successful where they normally fail: self
      modeling with feedforward. Data reports show that individuals generalized and
      maintained their new skills and attitudes, but the sustainability of programs has
      been variable. Analysis of the variations indicates the importance of program
      level feedforward that brings the future into the present. The discussion
      includes consideration of how individual-level and community-level practices can
      inform each other.

PMID- 17437186
TI  - Is readmission a valid indicator of the quality of inpatient psychiatric care?
AB  - Early return to hospital is a frequently measured outcome in mental health system
      performance monitoring yet its validity for evaluating quality of inpatient care
      is unclear. This study reviewed research conducted in the last decade on
      predictors of early readmission (within 30 to 90 days of discharge) to assess the
      association between this indicator and quality of inpatient psychiatric care.
      Only 13 studies met inclusion criteria. Results indicated that risk is greatest
      in the 30-day period immediately after discharge. There was modest support that
      attending to stability of clinical condition and preparing patients for discharge
      can protect against early readmission. A history of repeated admission increases
      risk, suggesting that special efforts are required to break the revolving door
      cycle. The authors identified a need for more standardization in measurement of
      client status at discharge and related care processes, more intervention studies
      on discharge practices, and studies of the effect of community care on early
      readmission.

PMID- 17437188
TI  - African American adolescent mothers and grandmothers: a multigenerational
      approach to parenting.
AB  - This study is an adaptation and extension of Apfel and Seitz's (Family Relations,
      40(4), 421-429, 1991) models of adolescent parenting and adolescent-grandmother
      relationships to a sample of 148 African American, first-time adolescent mothers
      and their 6-month-old infants. The Parental Supplemental model, in which
      adolescent mothers and grandmothers shared caregiving, described 63% of Apfel and
      Seitz's (1991) sample and 66% of the current sample. Shared caregiving was not
      associated with conflict in the adolescent mother-grandmother relationship.
      Adolescent mothers who had caregiving responsibilities and a supportive
      adolescent-grandmother relationship also reported competence in their parenting
      role. Findings provide support for Apfel and Seitz's Parental Apprentice model,
      in which young mothers gain competence through direct caregiving experience in
      the context of a supportive relationship.

PMID- 17437189
TI  - Exploring the complexities of familism and acculturation: central constructs for
      people of Mexican origin.
AB  - We examined the relationships between three dimensions of familism: importance of
      family, family support, and family conflict with acculturation, assessed
      orthogonally (Mexican and American cultural contributions assessed
      independently), and the relative contribution these factors make to psychological
      adjustment among 248 (124 women, 124 men) adults of Mexican origin. After
      controlling for sociodemographic characteristics, positive associations were
      found between importance of family and the biculturalism of Mexican and American
      cultural identity; family support and Mexican cultural identity; but no
      associations between family conflict and level of acculturation. Psychological
      well-being was positively associated with Mexican cultural identity and family
      support, whereas psychological distress was associated with greater family
      conflict and lower family support. The greater relative contribution of Mexican
      cultural identity to familism and well-being, and the importance of assessing
      acculturation orthogonally are discussed.

PMID- 17437190
TI  - Community types and mental health: a multilevel study of local environmental
      stress and coping.
AB  - Research has found that neighborhood structural characteristics can influence
      residents' mental health. Few studies, however, have explored the proximal
      reasons behind such influences. This study investigates how different types of
      communities, in terms of environmental stressors (social and physical disorder
      and fear of crime) and social resources (informal ties and formal organizational
      participation), affect well-being, depression, and anxiety in adult residents.
      Data are from a survey of 412 residents nested in 50 street blocks. Block
      stressors and resources were cluster analyzed to identify six block types. After
      controlling for several individual- and block-level characteristics, results from
      multilevel models suggest that in communities facing relatively few stressors,
      higher levels of formal participation are associated with better mental health.
      Because high levels of formal participation were not found in communities with
      higher levels of stressors, the impact of participation in such contexts could
      not be examined. However, results suggest that in communities where stressors are
      more common, isolation from neighbors may have a protective effect on mental
      health.

PMID- 17437191
TI  - Social support, sense of community in school, and self-efficacy as resources
      during early adolescence: an integrative model.
AB  - Influences of different sources of social support (from parents and friends),
      school sense of community, and self-efficacy on psychosocial well being (as
      measured by self-reported life satisfaction and psychological symptoms) in early
      adolescence were investigated in an integrative model. The model was tested using
      structural equation modeling. Multi-group comparisons were used to estimate
      differences between sex and age groups. The survey sample was composed of 7,097
      students in Northern Italy (51.4% male) divided into three age cohorts
      (equivalent to 6th, 8th, and 10th grades with median ages of 11, 13, and 15).
      Findings obtained using SEM were consistent with self-efficacy and school sense
      of community mediating effects of social support on psychosocial adjustment. The
      multi-group comparison indicates a need for more complex developmental models and
      more research on how changing forms of support interact with each other as their
      effects also change during this important stage of the life. Implications for
      primary prevention and cross-cultural comparisons are discussed.

PMID- 17437192
TI  - Impact of fetal-maternal microchimerism on women's health--a review.
AB  - Microchimerism is defined by the presence of circulating cells, bi-directionally
      transferred from one genetically distinct individual to another. It occurs either
      physiologically during pregnancy, or iatrogenically after blood transfusion and
      organ transplants. The migrated cells may persist for decades. Much controversy
      exists around the role of microchimeric cells in the pathogenesis of various
      diseases and around their role in tissue repair. Microchimerism has been
      investigated in different autoimmune disorders, such as systemic sclerosis,
      systemic lupus erythematosus, autoimmune thyroid diseases, primary biliary
      cirrhosis and juvenile inflammatory myopathies. Recent data have demonstrated the
      promising role of microchimeric cells in the maternal response to tissue injuries
      by differentiating into many lineages. Therefore, further understanding of fetal
      maternal microchimerism may help in anticipating its implications in disease as
      well as in more general women's health issues.

PMID- 17437193
TI  - Sonographic diagnosis of fetal cerebral ventriculomegaly: an update.
AB  - Dilatation of the fetal cerebral ventricles (ventriculomegaly) is a generic
      sonographic sign that is common to several pathological entities carrying
      different prognoses. The main causes of fetal ventriculomegaly are aqueductal
      stenosis, Chiari II malformation, Dandy-Walker complex, and agenesis of the
      corpus callosum. Ventriculomegaly is easily recognized by ultrasound by measuring
      the atrial width. This simple measure allows the recognition of mild forms of
      ventricular dilatation and is used in screening for ventriculomegaly. However,
      although the diagnosis of ventriculomegaly is easy, the prenatal identification
      of the cause of ventricular dilatation is a more difficult task. For this purpose
      the evaluation of the posterior fossa in association with the visualization of
      the corpus callosum is useful. Research into the causes of ventriculomegaly is
      clinically useful, since the prognosis mainly depends on the etiology and on the
      presence of associated abnormalities. In this article the role of prenatal
      sonography in determining the cause of the ventriculomegaly is reviewed, as well
      as the prognostic value of the prenatal sonographic findings.

PMID- 17437195
TI  - Impact of progesterone on cytokine-stimulated nuclear factor-kappaB signaling in
      HeLa cells.
AB  - OBJECTIVE: A key event in the pathways leading to preterm labor may be the
      activation of nuclear factor-kappaB (NF-kappaB) in the fetal membranes and the
      cervix. Anti-inflammatory agents, such as the corticosteroids, inhibit the
      activation of NF-kappaB. We proposed to investigate the effects of progesterone
      pretreatment on cytokine-stimulated activation of NF-kappaB in HeLa cells, a
      human cervical epithelial cell line. METHODS: HeLa cells were pretreated with 10(
      7) M progesterone for 24 hours and exposed to 1 ng/mL interleukin-1beta (IL
      1beta) for 1 hour. Nuclear and cytosolic extracts were subjected to Western blot
      analysis using anti-p65 and anti-inhibitory protein-kappaBalpha (anti
      IkappaBalpha) antibodies. Densitometric data (n=5) were compared using Kruskal
      Wallis test. RESULTS: Pretreatment with progesterone interfered with IL-1beta
      induced IkappaBalpha degradation. However, progesterone pretreatment resulted in
      a significant decrease in NF-kappaB protein subunit p65 in the cytoplasm.
      Pretreatment with progesterone did not reduce the amount of nuclear p65 and did
      not interfere with nuclear translocation of p65. CONCLUSION: Our observations
      suggest that any possible role played by progesterone in preterm labor prevention
      is not exerted through anti-inflammatory mechanisms of NF-kappaB down-regulation.

PMID- 17437194
TI  - Human beta-defensin-2: a natural antimicrobial peptide present in amniotic fluid
      participates in the host response to microbial invasion of the amniotic cavity.
AB  - OBJECTIVE: Human beta-defensin-2 (HBD-2) is a potent antimicrobial peptide that
      is part of the innate immune response. The purpose of this study was to determine
      whether HBD-2 is present in amniotic fluid and if its concentration changes with
      microbial invasion of the amniotic cavity (MIAC) and labor. STUDY DESIGN:
      Amniotic fluid was retrieved by amniocentesis from 318 patients in the following
      groups: (1) mid-trimester (n=75); (2) term not in labor (n=28) and in labor
      (n=51); (3) preterm labor and intact membranes without MIAC who delivered at term
      (n=36), who delivered preterm without MIAC (n=52), and preterm labor with MIAC
      who delivered preterm (n=25); and (4) preterm premature rupture of membranes
      (preterm PROM) with (n=25) and without MIAC (n=26). MIAC was defined as a
      positive amniotic fluid culture for microorganisms. Amniotic fluid HBD-2
      concentrations were determined using a sensitive and specific ELISA. Non
      parametric statistics were used for analysis. RESULTS: (1) HBD-2 was detected in
      all amniotic fluid samples; (2) the concentration of HBD-2 did not change with
      gestational age from mid-trimester to term (p=0.8); (3) intra-amniotic infection
      was associated with a significant increase in amniotic fluid concentrations of
      HBD-2 in both women with preterm labor and intact membranes, and women with
      preterm PROM (p<0.05 for each comparison); (4) patients with preterm labor and a
      negative amniotic fluid culture who delivered preterm had a higher median
      amniotic fluid HBD-2 concentration than those with preterm labor who delivered at
      term (p=0.001); and (5) among patients with preterm labor without MIAC, those who
      had intra-amniotic inflammation (amniotic fluid white blood cell count>100 cells
      per mL) had a higher median amniotic fluid concentration of HBD-2 than those
      without this condition (p<0.002). CONCLUSION: (1) Amniotic fluid contains HBD-2,
      a natural antimicrobial peptide, and this may account for some of the
      antimicrobial activity of amniotic fluid; (2) amniotic fluid HBD-2 concentrations
      are increased in women with MIAC, regardless of the membrane status (intact
      membranes or PROM); and (3) we propose that amniotic fluid HBD-2 is part of the
      innate immune system within the amniotic cavity.

PMID- 17437196
TI  - Paradoxical scalloped placenta with polyhydramnios in twin-twin transfusion
      syndrome.
AB  - OBJECTIVE: To describe the paradoxical occurrence of a scalloped placenta in the
      presence of polyhydramnios and assess its clinical significance in pregnancies
      complicated by twin-twin transfusion syndrome (TTTS) treated with laser therapy.
      METHODS: All patients who underwent laser therapy for TTTS between January 2003
      and April 2004 were studied. TTTS was diagnosed and staged using the Quintero
      staging system. Normally the placenta is characterized by undulations of the
      fetal-placental surface visible by ultrasound (scalloped placenta). Patients with
      polyhydramnios will typically have a flattened, smooth, non-scalloped placenta.
      Operative tapes were reviewed and placental type assigned. Pre-, intra-, and
      postoperative characteristics of each study patient were obtained. RESULTS:
      Fifteen of 120 patients (12.5%) were noted to have a scalloped placenta despite
      having polyhydramnios. There was no difference in mean gestational age at laser
      treatment (20.3+/-0.5 vs. 19.6+/-0.6 weeks, p=0.66) or in stage (p=0.07) between
      the two groups. The median and range preoperative maximum vertical pocket (MVP)
      in the recipient gestational sac differed significantly between the scalloped and
      non-scalloped patients (8.3 (8-12) vs. 10.5 (8-17), p=0.001). All 15 patients
      (100%) with a scalloped placenta required an amnioinfusion to expose all vascular
      anastomoses, while amnioinfusion was necessary in only 28 of the 105 patients
      (26.7%, p<0.001) with a non-scalloped placenta. Postoperative patent placental
      vessel was identified by surgical pathology in 6.7% of the scalloped placenta
      group vs. 1.9% of the non-scalloped placenta group (p=NS). CONCLUSION: The
      definition of TTTS requires an MVP>or=8 cm in the recipient sac. Most patients
      will have a flattened placenta as a result of polyhydramnios in this sac. Our
      data show that a paradoxical scalloped placenta may still be present in
      approximately 12.5% of patients. This preoperative sonographic finding alerts to
      the potential need for amnioinfusion during laser therapy for TTTS to disclose
      all vessels to avoid missing placental vascular anastomoses. Amniocenteses should
      be avoided if possible in patients considering laser therapy to minimize the
      likelihood of iatrogenic placental scalloping.

PMID- 17437197
TI  - Outcome of subsequent delivery after a previous early preterm cesarean section.
AB  - OBJECTIVE: To determine the vaginal birth after cesarean section (VBAC) rate and
      risk of uterine rupture in women with a previous early preterm cesarean section.
      METHODS: Women who delivered their first child by cesarean section between 26 and
      34 weeks of gestation were included in a retrospective cohort study. Medical
      charts were reviewed for characteristics of the index pregnancy and delivery.
      Information of the subsequent delivery was obtained from the medical charts or
      from information of the attending gynecologist if the delivery was elsewhere.
      RESULTS: Two hundred and forty-six women were included: 131 (53.3%) women had a
      subsequent pregnancy, 64 (26.0%) had no subsequent pregnancy, and from 51 (20.7%)
      women no information could be obtained. Of the 131 women with a subsequent
      pregnancy, 93 (71.0%) underwent a trial of labor (TOL) and 80 (86.0%) achieved a
      vaginal delivery, resulting in a VBAC rate of 61.1%. One uterine rupture occurred
      with favorable neonatal outcome. The uterine rupture rate for the whole cohort
      was 0.8% (95% CI 0.02-4.0) and for the group of women undergoing a TOL 1.1% (95%
      CI 0.03-5.8). CONCLUSION: In this small series of women with a previous early
      preterm cesarean section the VBAC rate was high (61.1%) and the uterine rupture
      rate was 1.1%.

PMID- 17437198
TI  - Impact of clinical and histologic correlates of maternal and fetal inflammatory
      response on gestational age in preterm births.
AB  - OBJECTIVE: To evaluate the impact of clinical and histopathologic correlates
      related to maternal and fetal inflammatory responses (MIR and FIR) on degree of
      preterm birth. METHODS: Pathology reports and clinical data from 577 singleton
      preterm births (<37 weeks of gestation) that took place between 1998 and 2004
      were analyzed according to decreasing gestational age (>or=33 weeks, 29-32 weeks,
      and <29 weeks). MIR was defined by presence of subchorionitis, chorioamnionitis,
      deciduitis, or free membranitis; FIR was defined by presence of funisitis or
      chorionic plate vasculitis. The associations between MIR alone and MIR with FIR
      and gestational age subgroups were assessed using logistic regression. RESULTS:
      The presence of FIR in addition to MIR was more strongly associated with degree
      of prematurity than the presence of MIR alone, especially for those born at <29
      weeks (OR=10.1 (95% CI 4.3-23.7) and OR=5.3 (95% CI 2.3-12.5), respectively).
      These associations remained significant after adjusting for maternal race,
      clinical signs of chorioamnionitis, medically indicated birth, and intrapartum
      corticosteroid, tocolysis and antibiotic use, and after stratification by
      clinical signs of chorioamnionitis and medically indicated birth. CONCLUSIONS:
      The combined presence of MIR and FIR is associated with a higher risk of extreme
      preterm birth (<29 weeks) than MIR alone, suggesting a contributory role of FIR
      in the pathophysiology of preterm birth.

PMID- 17437199
TI  - Fetal ST segment heart rate analysis in labor: improvement of intervention
      criteria using interpolated base deficit.
AB  - OBJECTIVE: The addition of ST waveform analysis (STAN, Neoventa, Sweden) to fetal
      heart rate (FHR) tracings has been demonstrated to improve fetal outcome and
      reduce operative delivery rates, though the actual level of fetal acidosis at
      which STAN indicates intervention has not been assessed. We sought to determine
      if FHR ST segment analysis recommends intervention at appropriate levels of fetal
      acidosis. METHODS: FHR tracings of 10 acidotic and 10 non-acidotic infants with
      FHR tracings having a minimum of one STAN flag were retrospectively analyzed.
      Fetal base deficit (BD) was calculated by interpolation throughout the FHR
      tracing and STAN 'action' and 'ignore' flags assigned a fetal BD value. A
      secondary analysis was performed with a revised interpretation of FHR reassuring
      status. RESULTS: The mean (+/-SD) BD of the first STAN action was significantly
      greater than the first 'ignore' (4.0+/-2.1 vs. 3.0+/-0.8 mmol/L, p<0.05).
      Clarified STAN criteria for reassuring vs. non-reassuring FHR resulted in a first
      action BD of 6.0+/-2.0 mmol/L with 90% sensitivity and 100% specificity for
      prediction of fetal acidosis. CONCLUSION: The STAN monitor discriminates
      increasing levels of fetal BD. With clarification of the criteria for reassuring
      FHR, the calculated BDs of action flags are an appropriate threshold for emergent
      intervention, successfully predict acidotic fetuses, and avoid unnecessary
      intervention.

PMID- 17437200
TI  - Maternal and neonatal outcome after cesarean section: the impact of anesthesia.
AB  - BACKGROUND: Among the anesthetic technologies used, regional anesthesia is
      becoming the most common in cesarean section (CS) deliveries. Aim. This
      retrospective survey examined the variables taken into account when selecting the
      anesthetic technique to be used, and how this choice affects the outcome for the
      mother and the newborn. METHODS: One thousand eight hundred and seventy elective
      and emergency CS were evaluated for anesthetic technique used, indications, and
      maternal and neonatal outcome. RESULTS: Of the 611 elective CS (32.6%), 206
      (33.8%) were performed under general anesthesia and 405 (66.2%) under regional
      anesthesia. Of the 1259 emergency CS performed (67.4%), 525 (41.9%) were under
      general anesthesia and 734 (58.1%) under regional anesthesia. Conditions
      associated with a newborn 1-minute Apgar score of <7 were general anesthesia and
      multiple pregnancy (p<0.01); a 5-minute Apgar score of <7 was only associated
      with multiple pregnancy. The most important factor for very low Apgar scores was
      the presence of fetal malformations. Whatever the chosen technique, neither
      maternal deaths directly or indirectly due to the anesthesia nor major maternal
      and perinatal complications were found. CONCLUSIONS: This survey confirms the
      preference for regional anesthesia during elective cesarean sections and for
      general anesthesia in emergency situations. Moreover, newborn outcome was found
      not to be influenced either by the technique used or by the character of the
      procedure.

PMID- 17437201
TI  - Should we continue screening rhesus D positive women for the development of
      atypical antibodies in late pregnancy?
AB  - OBJECTIVE: The purpose of this study was to calculate the incidence of the new
      development of atypical antibodies (other than anti-rhesus D) in women attending
      for antenatal care, and to assess the clinical impact and cost-effectiveness of a
      second test to detect these antibodies. METHOD: A three-year retrospective
      analysis was undertaken to calculate the number of rhesus positive women who
      developed new antibodies in the last trimester of pregnancy. RESULTS: Of 13,143
      rhesus positive women, 20 (0.15%) developed new antibodies; fetal outcome was not
      compromised in any of these cases. CONCLUSION: Repeat testing in late pregnancy
      would appear an unnecessary expense in our population.

PMID- 17437202
TI  - Transabdominal cerclage: can we predict who fails?
AB  - OBJECTIVE: To examine the outcome of pregnancies in women with transabdominal
      cerclage (TAC) and to determine whether aspects of the obstetric history predict
      failure. METHODS: This was a cohort study of pregnant women referred for a
      transabdominal cerclage between 1978 and 2004. Records were reviewed for
      obstetric history and maternal demographics. Predictor variables were prior
      pregnancy loss, prior vaginal cerclage, associated factors for TAC, and maternal
      age. The outcome variable was delivery of an infant beyond 24 weeks who survived
      the neonatal period. Outcomes were compared using Student's t-test, standard z
      test, and Chi-square test. RESULTS: Eighty-eight women delivered 96 pregnancies
      after TAC placement. The fetal salvage rate prior to TAC was 18%, 93% after the
      procedure (p<0.001). Delivery beyond 37 weeks occurred in 70% of pregnancies.
      Maternal age, prior cerclage history, associated factors for TAC, or previous
      delivery of a viable infant did not predict the eight failures out of the 96
      pregnancies. CONCLUSION: Women with TAC had a higher rate of successful
      pregnancies than prior to TAC. Neither maternal age nor prior pregnancy loss
      predicted failure. However with such a high success rate, we would have needed
      948 women to do so. TAC is an option for women with a poor obstetric history
      including failed vaginal cerclage.

PMID- 17437203
TI  - STAN-recorded intrapartum loss of beat-to-beat variation associated with
      prolonged QT-interval: indicative for fetal hypocalcemia?

PMID- 17437204
TI  - Delayed severe HPA-5b neonatal alloimmune thrombocytopenia: a case report.

PMID- 17437205
TI  - Right atrial myxoma mimicking an atrial thrombus in the third trimester of
      pregnancy.

PMID- 17437207
TI  - The creation of Adam and God-placenta.

PMID- 17437208
TI  - Embryo-fetal toxicity signals for 17alpha-hydroxyprogesterone caproate in high
      risk pregnancies: a review of the non-clinical literature for embryo-fetal
      toxicity with progestins.
AB  - OBJECTIVE: A large National Institutes of Health (NIH) study showed that pharmacy
      compounded 17alpha-hydroxyprogesterone caproate (17-OHP-C) reduced the incidence
      of preterm birth. The study results included a signal that 17-OHP-C may be
      associated with an increase in the rate of miscarriages and stillbirths. The most
      probable cause of an increased incidence of miscarriage/stillbirths may be the
      use of 17-OHP-C in high-risk patients. The current search of the non-clinical
      literature was performed to identify whether there were any signals from studies
      in animals that might suggest concerns for the safe use of progestins generally,
      and 17-OHP-C specifically, in the prevention of preterm birth in humans. METHODS:
      An extensive literature search was performed for progesterone, 17
      hydroxyprogesterone, and 17-OHP-C, using Medline and Toxline databases,
      textbooks, and then the obtained publications. Because 17-OHP-C does not have a
      standardized clinical formulation or optimal route of administration identified,
      all formulations, vehicles, routes and doses were included in the search, as well
      as treatment during any stage of pregnancy. All publications obtained were
      reviewed for relevancy; those in German, French, Italian or Russian were
      translated. RESULTS: None of the relevant non-clinical studies conducted in mice,
      rats, rabbits, guinea pigs, horses or non-human primates met current standards
      for determining reproductive and developmental effects as part of the process of
      drug development. Most studies focused on the potential of 17-OHP-C for
      teratogenicity. Many studies used supra-pharmacologic and/or high multiples of
      human exposure in their study design. Overall, 17-OHP-C was consistently shown to
      be less potent than progesterone, and neither progesterone nor 17-OHP-C
      consistently adversely affected maternal weight, embryo-fetal viability or caused
      malformations. One study in rhesus monkeys raises concerns because
      resorption/abortion occurred at the human equivalent dose of 17-OHP-C, 10 mg/kg;
      this finding did not occur in cynomolgus monkeys. The absence of information
      regarding the serum levels of both progesterone and 17-OHP-C in the animal
      studies and in humans, as well as presumed inter-species metabolic differences,
      make it difficult to conclude that the findings with 17-OHP-C in rhesus monkeys
      and the signal in the NIH trial are related. A few studies in rats raised
      questions regarding potential effects on postnatal development, but in the
      absence of better study designs, the relevancy of these findings to human risk
      are also questionable at best. CONCLUSION: There is a signal for embryo-fetal
      toxicity associated with 17-OHP-C in the two largest clinical trials conducted to
      date; there is also a signal for embryo-fetal toxicity with 17-OHP-C in rhesus
      monkeys and possibly one in rodent species. The relationship between these
      signals is unclear given the absence of state-of-the-art reproductive toxicology
      studies and human pharmacokinetic studies.

PMID- 17437209
TI  - Placental histopathologic features in patients with thrombophilic mutations.
AB  - The purpose of this article is to review the histopathologic findings in the
      placenta of women with a known thrombophilic mutation. The findings range from
      normal to severe pathologic features including decidual vasculopathy, placental
      infarctions, syncytial knotting, maternal floor infarction, fetal thrombotic
      vasculopathy, vasculitis, and chronic villitis. They are, however, not
      pathognomonic of thrombophilic states, nor are necessarily markers of perinatal
      damage. The prospective evaluation of cases with known thrombophilic mutations
      and the application of tissue microarray examination of the placenta may allow
      identification of major histopathologic features and molecular parameters
      associated with maternal and/or fetal thrombophilic states. This may assist
      clinicians in their consultation with patients and optimize management in future
      pregnancies.

PMID- 17437210
TI  - Intensive insulin therapy in pregnancy: strategies for successful implementation
      in pregestational diabetes mellitus.
AB  - The role of intensive insulin therapy (IIT) in the reduction of long-term
      diabetes-related complications is well established. Normal blood glucose level
      prior to and during pregnancy is critical in reducing both short- and long-term
      morbidity and mortality in mother and infant. IIT in pregnancy, though
      occasionally challenging, is necessary to achieve and maintain normal blood
      glucose level during pregnancy. Current knowledge and recent advances in insulin
      formulations and delivery systems have improved our ability to achieve glycemic
      targets in pregnancy while limiting maternal and fetal morbidity. The objective
      of this review is to discuss contemporary strategies for successful use of IIT in
      pregnancy.

PMID- 17437211
TI  - Effects of vitamin E on the response of the fetal middle cerebral artery to the
      pressure test.
AB  - OBJECTIVE: To examine the effects of the maternal administration of vitamin E on
      the vasoreactivity of the middle cerebral artery (MCA) in preterm fetuses. STUDY
      DESIGN: The vasoconstrictive response of the proximal segment of the MCA to brief
      and partial external occlusions of the umbilical vein (pressure test) was studied
      in 22 fetuses between 21 and 35 weeks of gestation, before, and 3 to 7 days
      after, the maternal administration of oral vitamin E (50 mg daily). RESULTS: The
      vasoconstrictive activity of the MCA was eliminated in 15 fetuses (68.2%),
      unchanged in six (27.3%), and decreased in one (4.5%). In the latter seven cases,
      vasoconstriction of the proximal MCA in response to the pressure test was
      eliminated by increasing the vitamin E dosage to 100 mg/day. CONCLUSION: Vitamin
      E administered to the mothers had a pronounced effect on the proximal MCA
      reactivity in preterm fetuses.

PMID- 17437212
TI  - Deceleration area of fetal heart rate trace and fetal acidemia at delivery: a
      case-control study.
AB  - OBJECTIVE: To assess the correlation between the total deceleration area of the
      fetal heart rate (FHR) pre-delivery trace and intrapartum fetal acid-base status
      in a low risk population. STUDY DESIGN: We analyzed the electronic fetal
      monitoring (EFM) traces of 26 pregnancies with fetuses presenting acidemia at
      delivery and those of thirty controls. All laboring patients had at least 1 hour
      of EFM without interruption. The deceleration area was calculated, after digital
      analysis, with Autocad System 2004. RESULTS: We found that the number of
      decelerations (8.03 +/- 3.77 vs. 4.64 +/- 3.84) and the total deceleration
      area/hour (35.56 +/- 11.87 vs. 17.81 +/- 9.38) were significantly higher in the
      study group than in the control group. CONCLUSIONS: Our results show that
      quantitative analysis of the deceleration areas by digitized cardiotocography may
      have a discriminative capacity to predict fetal acidemia at delivery.

PMID- 17437213
TI  - Investigation of endothelin-1 type A receptor gene polymorphism (-231 G > A) in
      preeclampsia susceptibility.
AB  - OBJECTIVE: Preeclampsia is considered as a multifactorial disorder with a genetic
      predisposition. Alterations in the endothelin-1 (ET-1) system are considered to
      take part in triggering the vasoconstriction seen in preeclampsia. METHODS: In
      order to investigate the possible association of the -231 G > A polymorphism in
      the endothelin-1 type A receptor gene (EDNRA), previously shown to be associated
      with other conditions characterized by vasospasm, we examined 77 Caucasian
      preeclamptic women and 67 matched controls including normotensive subjects
      without history of thromboembolic event, abnormalities in blood pressure,
      proteinuria, edema and preeclampsia. The genotype was assessed by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) on genomic DNA
      extracted from blood samples. Case vs. control allele frequencies and genotype
      distributions were compared. RESULTS: No significant differences were found when
      considering both genotype (chi(2) = 0.58, p = 0.75) and allelic frequencies
      (chi(2) = 0.08, p = 0.77). Furthermore, no significant genotype-related
      difference was found in relation to clinical features, such as gestational age at
      onset, systolic and diastolic blood pressure, proteinuria on admission and
      delivery week. CONCLUSIONS: No association between the -231 G > A polymorphism in
      the EDNRA gene and preeclampsia as well as any correlation with the main clinical
      features of the disorder were found, thus excluding a role for this polymorphism
      in susceptibility to preeclampsia.

PMID- 17437214
TI  - Does cesarean section prevent mortality and cerebral ultrasound abnormalities in
      preterm newborns?
AB  - OBJECTIVE: Despite the increased use of the cesarean section (CS), the rates of
      cerebral palsy, a frequent consequence of brain damage, have remained stable over
      the last decades. Whether an actual decrease in cerebral palsy has been masked by
      increased survival of infants delivered by CS or not, remains undefined. To
      investigate the role of CS, we compared risks of mortality and brain damage, as
      defined by ultrasound (US) abnormalities, in preterm newborns by mode of
      delivery. METHODS: Information on fetal, maternal, and neonatal risk factors was
      collected from the paired clinical records of preterm newborns and mothers. Crude
      and adjusted odds ratios (OR) of mortality and ultrasound abnormalities,
      according to mode of delivery (i.e., vaginal, elective CS, and emergency CS) were
      calculated. All the analyses were controlled for possible confounding by
      indication. RESULTS: In newborns of gestational age <32 weeks, no effect of CS on
      cerebral US abnormalities was found (OR 0.71 and 0.73 for emergency CS and
      elective CS, respectively). None of the maternal and neonatal factors were
      associated with both cerebral US abnormalities and mode of delivery. Among
      newborns of gestational age >or=32 weeks, after controlling for known and
      potential confounders in a multivariate model, the adjusted ORs remained close to
      one for both elective CS and emergency CS. CONCLUSIONS: CS does not reduce
      overall mortality in preterm newborns. No protective effect of CS on US
      abnormalities was found after stratifying by gestational age and controlling for
      possible confounding. These results do not encourage the widespread use of CS in
      preterm labor.

PMID- 17437215
TI  - The influence of maternal epidural analgesia upon intrapartum fetal oxygenation.
AB  - OBJECTIVE: The use of maternal epidural analgesia in labor may be associated with
      non-reassuring fetal heart rate (FHR) patterns. We aimed to assess changes in
      fetal oxygen saturation (FSpO(2)) during epidural analgesia in labor. METHODS:
      This was a prospective observational study. Twenty healthy parturients were
      enrolled following the inclusion criteria. Informed consent was obtained. Mode of
      delivery, use of oxytocin, maternal blood pressure, umbilical cord blood
      analysis, Apgar score, and neonatal outcomes were evaluated. Ropivacaine at a low
      concentration of 0.1% (1 mg/mL) co-administered with an opioid (fentanyl 2.5
      microg/mL) was used. The values of fetal oxygen saturation were registered
      continuously 10 minutes before the administration of the analgesic drug and
      during the following 30 minutes after administration. Pulse oximetry was used
      simultaneously with cardiotocography (CTG). RESULTS: The average value for fetal
      oxygen saturation before the analgesic drug administration was 44.3 +/- 8.8%;
      during the first 10 minutes following administration it was 41.3 +/- 7.2% (p =
      0.25) and during the following 20 minutes it was 43.05% +/- 6.9% (p = 0.63).
      There was no direct relationship between non-reassuring CTG pattern appearance
      and FSpO(2) <30% (RR = 1.11, 95% CI 0.76-1.64). No significant correlation was
      found between FSpO(2) values within the first 30 minutes of epidural analgesia
      and neonatal acidotic status (pH <or=7.00; RR = 0.33, 95% CI 0.04-3.09, and base
      excess <or=-12 mmol/L; RR = 1, 95% CI 0.21-4.71). CONCLUSIONS: There were no
      differences in FSpO(2) values in the first 30 minutes following administration of
      analgesic drugs and most of the cases with non-reassuring CTG patterns had values
      of FSpO(2) constantly >or=30%.

PMID- 17437216
TI  - Antibiotic administration to patients with preterm premature rupture of membranes
      does not eradicate intra-amniotic infection.
AB  - OBJECTIVE: Antibiotic administration has become part of the standard of care for
      patients with preterm premature rupture of membranes (PROM). Yet, the natural
      history of intrauterine infection/inflammation during antibiotic therapy remains
      largely unknown. This study was conducted to determine if antibiotic
      administration to the mother eradicates intra-amniotic infection and/or reduces
      the frequency of intra-amniotic inflammation, a risk factor for impending preterm
      labor/delivery and adverse neonatal outcome. METHODS: A subset of patients with
      preterm PROM admitted to our institution underwent amniocenteses before and after
      antibiotic administration in order to guide clinical management. Amniotic fluid
      analysis consisted of a Gram stain, culture for aerobic and anaerobic bacteria as
      well as genital mycoplasmas, and amniotic fluid white blood cell (WBC) count.
      Microbial invasion of the amniotic cavity (MIAC) was defined as a positive
      amniotic fluid culture. Intra-amniotic inflammation was defined as an amniotic
      fluid WBC count >or=100/mm(3). Patients were given antibiotics and steroids after
      the 24(th) week of gestation. Antibiotic treatment consisted of ampicillin and
      erythromycin for 7 days for patients without evidence of intra-amniotic
      inflammation or MIAC, and ceftriaxone, clindamycin and erythromycin for 10-14
      days for those with intra-amniotic inflammation or MIAC. RESULTS: Forty-six
      patients with preterm PROM whose first amniocentesis was performed between 18 and
      32 weeks (median 27.4 weeks) were included in the study. The overall prevalence
      of intra-amniotic inflammation in the first amniocentesis was 39% (18/46). Seven
      had a positive amniotic fluid culture for microorganisms. At the time of the
      second amniocentesis, six of the seven patients with a positive amniotic fluid
      culture had microorganisms. Of 18 patients with intra-amniotic inflammation at
      admission, only three showed no evidence of inflammation after antibiotic
      treatment. Among patients with no evidence of intra-amniotic inflammation at
      admission, 32% (9/28) developed inflammation despite therapy. Five of these nine
      patients had positive amniotic fluid cultures. CONCLUSIONS: (1) Antibiotic
      administration (ceftriaxone, clindamycin, and erythromycin) rarely eradicates
      intra-amniotic infection in patients with preterm PROM; (2) intra-amniotic
      inflammation developed in one-third of patients who did not have inflammation at
      admission, despite antibiotic administration; (3) a sub-group of patients with
      documented inflammation of the amniotic cavity demonstrated a decrease in the
      intensity of the inflammatory process after antibiotic administration.

PMID- 17437217
TI  - Partial molar pregnancy and coexisting fetus with diploid karyotype.
AB  - OBJECTIVES: To evaluate cases of partial hydatidiform mole coexisting with a live
      fetus, including an observation of our own, and to discuss the proper antenatal
      management of women wishing to continue with a partial molar pregnancy. METHOD: A
      PubMed search was then undertaken, extending over the time period from 1975 to
      2006, using the keywords 'partial hydratidiform mole', 'hydatidiform mole' and
      'coexisting fetus'. RESULTS: At 16 weeks of gestation, an ultrasonographic
      examination revealed a normal fetus with an extremely large, multicystic
      placenta. The woman was informed of future risks but wished to continue with the
      pregnancy. The pregnancy progressed until 28 weeks without any complication but
      ended spontaneously with a vaginal delivery; the fetus had died in utero.
      Pathologic examination of the placenta revealed areas of hydropic degeneration
      and necrosis. Including our own observation, 17 cases of partial hydatidiform
      mole associated with a fetus of normal karyotype have been documented.
      CONCLUSION: Although the rate of adverse perinatal outcome is high, we still
      believe that if amniocentesis or fetal blood sampling reveals a normal karyotype,
      then continuing the affected pregnancy with close follow-up in tertiary centers
      is a feasible choice.

PMID- 17437218
TI  - Prenatal diagnosis of body stalk anomaly in the first trimester of pregnancy.

PMID- 17437219
TI  - Invasion of the amniotic cavity by an uncultured bacterium, a Gram-positive
      coccus.

PMID- 17437220
TI  - Depression and anxiety during pregnancy: a risk factor for obstetric, fetal and
      neonatal outcome? A critical review of the literature.
AB  - OBJECTIVE: Research from the past two decades has suggested a link between
      prenatal maternal psychological distress and adverse obstetric, fetal and
      neonatal outcome. Comparability of study results, however, is complicated by a
      diversity of definitions and measurements of prenatal maternal stress and
      different time points of assessment. Our aim was to critically review studies
      assessing maternal anxiety and depression during pregnancy and their impact on
      obstetric, fetal and neonatal outcome. METHODS: We carried out a computerized
      literature search of PubMed, PsycLIT and EMBASE (1990-2005) and a manual search
      of bibliographies of pertinent articles. In total 35 studies were identified that
      fulfilled the inclusion criteria. RESULTS: Elevated levels of depression and
      anxiety were found to be associated with obstetric outcome (obstetric
      complications, pregnancy symptoms, preterm labor and pain relief under labor),
      and had implications for fetal and neonatal well-being and behavior. However,
      prediction of the impact of mood and anxiety disorders during pregnancy is very
      limited due to methodological problems. Most notably, the majority of the studies
      included pregnant women with elevated symptoms of depressed mood and anxiety and
      did diagnose mood and anxiety disorders. Also, potentially confounding and
      protecting factors as well as biological mechanisms with a possible role in
      adverse outcome in pregnant women with depression and anxiety disorders have
      received little attention. CONCLUSIONS: Enhanced levels of depression and anxiety
      symptoms during pregnancy contribute independently of other biomedical risk
      factors to adverse obstetric, fetal and neonatal outcome. However, conclusions
      for women with mood or anxiety disorders are limited.

PMID- 17437221
TI  - Effect of maternal congenital heart defects on labor and delivery outcome: a
      population-based study.
AB  - OBJECTIVE: The primary objective of this study was to characterize the delivery
      outcome of parturients with congenital heart defects (CHD), from maternal and
      from neonatal perspectives. STUDY DESIGN: A retrospective population-based study
      was conducted, covering a 13-year period (1989-2002) with an aggregate of 151,487
      deliveries of all women with and without CHD. Maternal demographics, obstetrical
      and medical history, delivery outcome, and neonatal outcome were drawn from a
      computerized perinatal database. RESULTS: Sixty-seven women with CHD had 156
      deliveries. The severity of CHD, based on the New York Heart Association (NYHA)
      classification, was I or II in 99.1% of the deliveries. CHD patients had
      significantly higher rates of labor induction and neonatal malformations.
      Maternal CHD was discovered as an independent risk factor associated with
      neonatal malformations (OR 2.10, 95% CI 1.18-3.72). No significant differences
      were noted between women with CHD and the controls regarding maternal morbidities
      and Apgar scores. CONCLUSIONS: The labor outcome of CHD patients with NYHA
      classification I and II resembles that of non-CHD women in a tertiary center
      setting. Neonates of CHD mothers have higher rates of congenital malformations
      even among asymptomatic or mildly symptomatic mothers. A careful sonographic
      follow-up is warranted among all pregnancies of CHD patients.

PMID- 17437222
TI  - Effect of a specialized prenatal clinic on medical student attitudes toward women
      with drinking problems.
AB  - OBJECTIVE: To determine if student attendance at a specialized prenatal clinic
      would yield any change in their comfort level and in their attitudes toward
      pregnant women with drinking problems. METHODS: A total of 117 third-year
      students rotating consecutively on our core obstetrics-gynecology clerkship
      consented to enrolling in this prospective cohort study between February 2004 and
      June 2005. Each was assigned either to attend a half-day prenatal clinic designed
      specifically for women with alcohol and substance use disorders (study group) or
      not to attend the clinic (control group). The students answered anonymously a 15
      question survey (using a 5-point Likert scale from 'strongly disagree' to
      'strongly agree') at the beginning and at the midway point of the eight-week
      clerkship. Scores averaged for each question at the two points were compared
      within and between the two groups using paired-samples and independent-samples t
      tests. RESULTS: No differences in responses to the survey were found between the
      study and control groups at the beginning of the clerkship. Students who attended
      the clinic became more comfortable in inquiring about patient alcohol consumption
      (p<0.001) and about social problems such as domestic violence (p<0.001). After
      attending the clinic, students reported that alcoholism was associated less with
      a weak will (p<0.01) and that group therapy has more importance (p<0.05). In
      contrast, the control group disagreed less that alcohol use was more of a moral
      and legal problem than a medical problem (p<0.05). CONCLUSIONS: An experience at
      this special prenatal clinic improved medical student awareness of complexities
      faced by problem drinkers, enhanced their comfort in talking to pregnant alcohol
      drinkers, and favored more sympathy toward alcoholism in general but not
      necessarily during pregnancy.

PMID- 17437223
TI  - Isolated oligohydramnios in term pregnancy as an indication for induction of
      labor.
AB  - OBJECTIVE: To evaluate the outcome of active induction of labor for isolated
      oligohydramnios in low-risk term gestation. METHODS: This retrospective study
      analyzed the obstetric and perinatal outcome of 412 singleton term pregnancies
      with cephalic presentation and no maternal risk factors or fetal abnormalities.
      Two groups were compared: 206 deliveries after induced labor for isolated
      oligohydramnios, and 206 deliveries matched for gestational age following
      spontaneous labor with normal amniotic fluid index. RESULTS: The overall rate of
      cesarean deliveries and cesarean deliveries for nonreassuring fetal status, and
      operative vaginal delivery rates and those for nonreassuring fetal status were
      higher in the oligohydramnios group than in the control group. There were no
      differences between groups in neonatal outcome or perinatal morbidity or
      mortality. CONCLUSION: Active induction of labor in term low risk gestations with
      isolated oligohydramnios translated into higher labor induction, operative
      vaginal delivery and cesarean section rates. This led to increased maternal risk
      and an increase in costs with no differences in neonatal outcome.

PMID- 17437224
TI  - Amino acids in amniotic fluid in the 15th-16th weeks of gestation and preterm
      labor.
AB  - OBJECTIVE: To investigate amino acids in amniotic fluid collected at the time of
      genetic amniocentesis. METHODS: We analyzed 128 fluids from the 15(th) week of
      gestation and 53 from the 16(th) week of gestation from normal pregnancies, and
      eight in the 15(th) week and seven in the 16(th) week from pregnancies that lead
      to preterm deliveries. We calculated the mean values for each week and the ratios
      between each pair of amino acids. The data for both groups (normal and preterm
      delivery) were compared. RESULTS: The most abundant amino acid in both groups was
      alanine. The comparisons of the groups showed significant differences for
      isoleucine in the 15(th) gestational week (p<0.05). Some amino acids had
      different evolutions between both gestational ages on comparing the normal group
      and preterm group. Eighteen ratios in the 15(th) week showed significant
      differences (mainly in the ratios of arginine and taurine), and three in the
      16(th) week. CONCLUSIONS: The amino acid profiles in amniotic fluid, particularly
      in the 15(th) week of gestation, showed differences in the pregnancies that lead
      to preterm delivery.

PMID- 17437225
TI  - Evaluation of the use of umbilical artery Doppler flow studies and outcome of
      pregnancies at a secondary hospital.
AB  - OBJECTIVE: To investigate the use of a personal computer (PC)-based, continuous
      wave Doppler machine by a trained midwife at a secondary hospital to assess
      umbilical artery flow velocity waveforms (FVW) in referred women. METHODS:
      Pregnant women referred for suspected poor fetal growth were evaluated from June
      2002 through December 2004. The Umbiflow apparatus, consisting of a Pentium 3 PC
      with an ultrasound transducer plugged into the USB port and software, was used to
      analyze the FVW of the umbilical artery. Pregnancies in which the resistance
      index (RI) was <75(th) percentile (P75) were not further evaluated for fetal well
      being unless the clinical condition of the mother changed. Pregnancies with an RI
      >or=P75 were followed up according to a specific protocol. Primary end points
      were intrauterine death and intrauterine growth restriction. RESULTS: A total of
      572 singleton pregnancies were followed up. Significantly more infants were small
      for-gestational-age when the RI was >P95 (55.6%) than those between P75 and P95
      (41.2%) or <P75 (27.2%). Perinatal mortality rates were 13.2, 39.1 and 41.7 for
      women with RIs <P75, P75-95 and >P95, respectively. CONCLUSIONS: A normal Doppler
      FVW of the umbilical artery is less likely to be followed by perinatal death.

PMID- 17437226
TI  - Maternal and neonatal outcome following cerebrovascular accidents during
      pregnancy.
AB  - OBJECTIVE: To assess the clinical characteristics of maternal and neonatal
      outcome among women with cerebrovascular accidents (CVA) during pregnancy.
      METHODS: Our computerized database was used to identify patients with CVA during
      pregnancy and puerperium from January 1988 to March 2004. Their medical records
      were identified and reviewed. RESULTS: There were 16 cases of CVA among 173,803
      deliveries, giving a risk of almost one case per 10,000 pregnant women. Out of 16
      patients, 14 (88%) had a stroke and the remaining two cases were diagnosed with
      venous thrombosis. Of those 14 cases, nine (64%) had ischemic strokes and five
      (36%) had hemorrhagic strokes. Ten of the CVAs occurred antepartum, two
      intrapartum and four postpartum. Hypertensive disorders were diagnosed in 75%
      (12/16) of the patients. Out of these 12 patients with hypertension, 9 (75%)
      suffered from preeclampsia. One woman had a history of chronic hypertension.
      Smoking was associated with 63% (10/16) of the cases. There were two maternal
      deaths, both in women who had hemorrhagic strokes, and both in the first half of
      the study (1994 and 1996). Nine out of 16 women (56%), were delivered within 48
      hours of the CVA including 7 (78%) antepartum, and two (22%) intrapartum.
      Cesarean deliveries were performed in 11/16 women (69%) including 8/10 with CVAs
      occurring antepartum, 1/2 intrapartum and 2/4 postpartum. One case of neonatal
      mortality was identified in a patient who was delivered at 24 gestational weeks.
      CONCLUSIONS: (1) Hypertensive disorders and smoking were the most important
      factors associated with CVA during pregnancy. (2) Maternal mortality was high
      among patients with CVA during pregnancy. (3) Neonatal outcome was considered
      generally good in cases of CVA.

PMID- 17437227
TI  - Gestational age at initiation of 17-hydroxyprogesterone caproate (17P) and
      recurrent preterm delivery.
AB  - OBJECTIVE: To compare rates of recurrent preterm birth between women starting
      treatment with 17alpha-hydroxyprogesterone caproate (17P) at 16-20.9 weeks of
      gestation versus 21-26.9 weeks. METHODS: Women enrolled in an outpatient program
      of education, nursing assessment and weekly 17P injections beginning at 16-26.9
      weeks were eligible. Included were patients with singleton pregnancies and a
      history of preterm delivery (PTD). Pregnancy outcome was compared between women
      starting 17P at 16-20.9 weeks (n=156) and those starting 17P at 21-26.9 weeks
      (n=119) using Fisher's exact and Mann-Whitney U test statistics (p<0.05
      considered significant). RESULTS: Mean gestational age at delivery (36.8 +/- 3.0
      vs. 36.7 +/- 2.5) and rates of PTD at <37 weeks (40.4% vs. 48.7%), <35 weeks
      (16.7% vs. 16.8%) and <32 weeks (5.1% vs. 5.0%) were similar between the groups;
      all p > 0.05. CONCLUSIONS: Rates of preterm delivery were similar in patients
      initiating 17P at 16-20.9 or 21-26.9 weeks. A larger sample size is warranted in
      order to confirm our findings.

PMID- 17437228
TI  - The impact of maternal age, body mass index and maternal weight gain on the
      glucose challenge test in pregnancy.
AB  - OBJECTIVE: The aim of this study was to determine whether maternal age,
      prepregnancy and mid-trimester body mass index (BMI), or excessive mid-pregnancy
      weight gain predict abnormal glucose challenge test (GCT) results. METHODS: A
      retrospective chart review of 75 consecutive singleton pregnancies was performed.
      Patients were screened at 24-28 weeks of gestation with a 50-g oral GCT.
      Prepregnancy BMI and pregnancy weight gain up to the time of GCT testing, as well
      as other demographic data, were recorded. Statistical analysis included
      regression analysis and Student's t-test, receiver-operator characteristic curve
      and multivariate logistic regression. RESULTS: Maternal age and prepregnancy and
      mid-trimester BMI were significantly higher in women with an abnormal GCT
      (p<0.05). A direct correlation was found between these parameters and GCT results
      (R(2)=0.08, R(2)=0.102 and R(2)=0.116, respectively; p<0.05). Mid-trimester
      maternal BMI of >or=30 kg/m(2) and maternal age >or=32 years are the optimal
      predictors of abnormal GCT results. CONCLUSIONS: Mid-trimester maternal BMI of
      >or=30 kg/m(2) and maternal age >or=32 years are useful predictors of abnormal
      GCT results. We suggest that these factors should also be considered when
      selective screening for gestational diabetes mellitus is practiced.

PMID- 17437229
TI  - Body segmentation went wrong but promptly corrected.

PMID- 17437230
TI  - A mild case of amniotic fluid embolism?

PMID- 17437231
TI  - Management of fetal death after 20 weeks of gestation complicated by placenta
      previa.

PMID- 17437233
TI  - Renal effects of ibuprofen for the treatment of patent ductus arteriosus in
      premature infants.
AB  - In recent years ibuprofen has been proposed for the treatment of patent ductus
      arteriosus (PDA) as it has been proved to be equally as effective as indomethacin
      and shows fewer cerebral blood flow, intestinal and renal hemodynamic effects. A
      number of studies and several meta-analyses comparing both drugs are now
      available that debate whether indomethacin or ibuprofen should be used for PDA
      prophylaxis or closure. This review examines the available knowledge on the
      specific issue of the effects of ibuprofen on kidney function, as improved renal
      tolerance is a major argument in favor of its use in the routine treatment of
      PDA. There is sufficient evidence to consider that ibuprofen, at the currently
      proposed dosing regimen, has a similar efficacy to indomethacin but is better
      tolerated by the neonatal kidney when employed for the treatment of established
      PDA. However, adverse effects of ibuprofen have been evidenced both in trials on
      the use of ibuprofen for the prevention of PDA and of intraventricular hemorrhage
      periventricular hemorrhage (IVH-PVH), and in experimental studies on a neonatal,
      anesthetized animal model. Thus ibuprofen, as with other cyclooxygenase (COX)
      inhibitors, may not be exempt from causing renal adverse effects, especially in
      circumstances when renal prostaglandin activation is maximal (i.e., when
      administrated early after birth, in more immature patients and in certain
      situations such as in the anesthetized rabbit). However, although the issue has
      been addressed extensively in the last decades, there is insufficient evidence
      that therapeutic intervention in PDA is beneficial in terms of mortality or
      clinically significant morbidity outcomes. Studies aimed at resolving this key
      issue are still needed.

PMID- 17437234
TI  - Chorionic villus sampling significantly affects fetal cardiovascular function.
AB  - OBJECTIVE: To assess the effects of chorionic villus sampling (CVS) on fetal
      heart rate (FHR). METHODS: A prospective longitudinal study was conducted among
      300 patients undergoing transabdominal CVS between 8 and 13 weeks of gestation.
      Duration of the procedure, number of needle passes, sample weight, maternal age,
      fetal gender, and FHR response to CVS were recorded. RESULTS: The FHR before but
      not after CVS was inversely correlated with gestational age (r = -0.406, p <
      0.001). Conversely, following CVS, no correlation was observed between FHR and
      gestational age (r = -0.06, p = 0.27). The difference between FHR after CVS and
      that obtained before CVS (delta FHR) increased with increasing gestational age at
      sampling (r = 0.372, p < 0.0001), decreased with increasing specimen weight (r = 
      0.16, p = 0.01) and increased with increasing maternal age (r = 0.22, p <
      0.0001). Duration of the procedure, fetal gender and number of needle passes did
      not affect delta FHR. Multiple logistic regression indicated that gestational age
      at CVS and maternal age but not the other variables significantly affected delta
      FHR and together they accounted for over 22% of the variance (R(2) = 0.224, p <
      0.0001). CONCLUSIONS: In summary, our results suggest that acute fetal
      hemodynamic changes accompany CVS and that these changes vary with gestational
      age.

PMID- 17437235
TI  - The relationship between hiccups and heart rate in the fetus.
AB  - OBJECTIVE: The purpose of this study was to determine the effect of fetal hiccups
      on fetal heart rate from 20 weeks of gestation onward. METHODS: One thousand four
      hundred and fifty-six collected fetal heart rate tracings from three cohorts that
      participated in longitudinal studies of fetal neurobehavioral development were
      reviewed retrospectively for fetal hiccups. Tracings were recorded at four-week
      intervals from 20 weeks. A hiccup-free period before or after the episode of
      hiccups was used as the control fetal heart rate; thus each fetus was used as its
      own control. The paired t-test was used for statistical analysis. RESULTS: From
      28 weeks onward, the mean fetal heart rate increased with hiccups reaching
      statistical significance at 32 weeks. Fetal heart rate variability was unaffected
      by hiccups until 36 weeks, at which time it decreased during hiccup periods.
      CONCLUSION: This change in response to fetal hiccups may represent another
      neurodevelopment milestone for the fetus.

PMID- 17437236
TI  - Is there a preferred gestational age threshold of viability?: a survey of
      maternal-fetal medicine providers.
AB  - OBJECTIVE: To characterize variation and factors associated with the perceived
      gestational age for the threshold of viability among maternal-fetal medicine
      (MFM) providers. METHODS: We performed a web-based online survey of 1375 MFM
      providers. For this secondary analysis, a subset of survey questions targeted
      toward perceptions of the limit of viability was analyzed to identify how the
      respondents viewed the optimal threshold of viability gestational age.
      Comparative statistics were performed to assess various characteristics that
      influence the perceived threshold of viability. RESULTS: Five hundred and eight
      providers (37%), representing all 50 states and 13 countries, responded to the
      survey. The reported threshold of viability varied among survey respondents: 22
      weeks, 2.0%; 23 weeks, 37.2%; 24 weeks, 55.3%; 25 weeks, 3.4%; and 26 weeks,
      2.2%. No significant differences were noted in the reported threshold of
      viability with respect to practitioner age (<50 years old vs. > or =50 years old,
      p = 0.42), nursery availability (level III vs. other, p = 0.46), and years in
      practice (<10 years vs. > or =10 years, p = 0.86). Significant differences in the
      reported threshold of viability were noted with respect to practitioner gender
      with males tending to have a lower gestational age threshold than females (p =
      0.005). Significant differences were also noted among practitioners from academic
      vs. community/private practice settings (p = 0.008). A logisitic regression
      model, adusting for both gender and practice setting, revealed that male gender
      was independently associated with selection of a threshold of viability less than
      24 weeks of gestation: male gender OR 1.8 (95% CI 1.3-2.7, p = 0.002); academic
      practice setting OR 1.1 (95% CI 0.8-1.6, p = 0.50). CONCLUSIONS: Perceived
      threshold of viability among MFM providers varies with the majority of
      practitioners identifying 23-24 weeks of gestation. Significant difference,
      however, exists between practitioner genders.

PMID- 17437237
TI  - Evaluation of the utero-placental circulation by three-dimensional Doppler
      ultrasound in the second trimester of normal pregnancy.
AB  - OBJECTIVE: To define normative data with three-dimensional (3D) Doppler
      ultrasound in the second trimester spiral arteries and placental volume blood
      flow. METHODS: An entry criterion was a documented singleton pregnancy at 14-25
      weeks with normal outcome. Each patient had a 3D power Doppler exam. Automatic
      volume acquisition of the placental and spiral arteries blood flow was obtained.
      We calculated vascularization index (VI), flow index (FI) and vascularization
      flow index (VFI). The patients were further divided into subgroups based on two
      gestational week intervals. The outcome measure was normal pregnancy outcome.
      RESULTS: One hundred ninety-nine patients were included in this study. Placental
      and spiral arteries vascular indices slowly increased indicating progressive
      development of vascular network and increase in the volume blood flow. The range
      for placental VI was 11.43-14.63, FI was 37.44-40 and VFI was 4.77-6.06. The
      range for spiral arteries VI was 19-20.91, FI was 39.66-41.1 and VFI was 8.49
      8.92. The mean gestational age at delivery was 38.18 weeks. CONCLUSION: We
      defined normal 3D power Doppler vascular indices in pregnancies between 14 and 25
      weeks of singleton gestation. The study indicated that placental and spiral
      arteries volume blood flow increased with the advancement of gestational age.

PMID- 17437238
TI  - The relationship between utilization of prenatal care and Down syndrome live
      births.
AB  - OBJECTIVE: This study evaluated whether utilization of prenatal care, as measured
      by the Kessner index, affects the number of Down syndrome live births. METHODS: A
      retrospective analysis of birth certificate data of Down syndrome live births
      comparing 1989 to 2001 by year, maternal age, gestational age at first prenatal
      visit, and adequacy of prenatal care according to Kessner categories of adequacy
      of prenatal care. RESULTS: Down syndrome live births were inversely correlated
      with adequacy of prenatal care. Reductions in Down syndrome live births were seen
      in all categories of prenatal care in all age groups. In 2001 a minimum 30%
      reduction was seen in any category rising to a 58% reduction in women > or =35
      years with adequate prenatal care. The largest reductions were seen in women > or
      =35 years of age. CONCLUSIONS: Reductions in Down syndrome live births occurred
      in all age groups between 1989 and 2001. Utilization of prenatal care as measured
      by the Kessner index was associated with reductions in Down syndrome live births,
      with a greater reduction in women > or =35 years of age.

PMID- 17437239
TI  - Shoulder dystocia without versus with brachial plexus injury: a case-control
      study.
AB  - OBJECTIVE: To delineate factors that differentiate shoulder dystocia with and
      without brachial plexus injury (BPI). STUDY DESIGN: A case-control study culled
      from an established shoulder dystocia database. Cases of shoulder dystocia
      related BPI were identified and matched (1:1) with a control group of shoulder
      dystocia in which BPI did not result. Odds ratios (OR) and 95% confidence
      intervals (CI) were calculated. RESULTS: From 1980 to 2002, there were 89 978
      deliveries with 46 cases of dystocia and BPI. The rate of dystocia with BPI was
      0.5 per 1000 births and of permanent BPI, 0.9/10 000 deliveries. The two groups
      were similar for maternal demographics, diabetes, gestational age, induction, use
      of epidural, the duration of labor, operative vaginal delivery, rate of
      macrosomia, and maneuvers used to relieve the dystocia. Fracture of the clavicle
      occurred significantly less often among those without (2%) vs. with BPI (17%; OR
      0.10, 95% CI 0.01, 0.88). CONCLUSIONS: Neither antepartum nor intrapartum factors
      can differentiate the patient who will have shoulder dystocia with vs. without
      BPI.

PMID- 17437240
TI  - Maternal health outcomes two years after term breech delivery.
AB  - OBJECTIVE: To evaluate maternal health outcomes two years after term breech
      delivery. DESIGN: This was a non-randomized single-center prospective cohort
      study. Mothers were asked to fill out questionnaires at two years postpartum to
      judge their health in the previous three to six months. Outcomes of the planned
      cesarean section group were compared with outcomes of the planned vaginal
      delivery group, whether or not a vaginal birth was realized or an emergency
      cesarean section was performed. RESULTS: One hundred and eighty-three women
      completed a follow-up questionnaire at two years postpartum. Outcomes of the
      planned cesarean section group were compared with outcomes of the planned vaginal
      delivery group, whether or not a vaginal birth was realized or an emergency
      cesarean section was performed. No differences in maternal experiences concerning
      breastfeeding, taking care of her child and the relationship with her partner
      were found between the two groups. Also, no differences were found in all
      investigated maternal health items, or in sexual activity and fertility.
      CONCLUSION: Maternal health outcomes two years after term breech delivery were
      similar after planned cesarean section and planned vaginal delivery.

PMID- 17437241
TI  - Toxicity of corticosteroids and catecholamines for mice neuronal cell cultures:
      Role of preservatives.
AB  - OBJECTIVE: To confirm previous reports on dexamethasone and sulfite
      neurotoxicity, and to investigate methylprednisolone, dopamine, and dobutamine
      neurotoxicity. METHODS: Pure dexamethasone, injectable dexamethasone containing
      sodium metabisulfite (Soludecadron), pure methylprednisolone, injectable
      methylprednisolone (Solu-Medrol), pure dopamine, injectable dopamine containing
      potassium metabisulfite (Revivan), pure dobutamine, injectable dobutamine
      containing sodium metabisulfite (Dobutrex), and sodium metabisulfite were added
      to the medium of mixed glial-neuronal cell cultures at concentrations of 0.1, 1,
      10, and 100 microM. Cell damage induced by glucocorticoids was assessed by
      measuring the release of lactate dehydrogenase (LDH) from the injured cells into
      the extracellular fluid during the 24 hours of exposure to drugs. Cell damage
      induced by catecholamines was assessed using the fluorescent dye propidium iodide
      (PI) method 24 hours after exposure to the drugs. RESULTS: Methylprednisolone and
      Solu-Medrol did not affect neuronal death, which was increased by dexamethasone
      and Soludecadron at 100 microM and sodium metabisulfite at 10 and 100 microM.
      Neuronal death was significantly increased by dopamine, Revivan, dobutamine,
      Dobutrex, and sulfites at 10 and 100 microM concentrations. CONCLUSIONS: In vitro
      dexamethasone, Soludecadron, and sulfites increase neuronal cell death, while
      methylprednisolone and Solu-Medrol are not neurotoxic; dopamine and dobutamine
      were found neurotoxic independently from sulfite toxicity.

PMID- 17437242
TI  - Maternal plasma interleukin-6, interleukin-1beta and C-reactive protein as
      indicators of tocolysis failure and neonatal outcome after preterm delivery.
AB  - OBJECTIVE: To investigate whether maternal serum interleukin-6 (IL-6),
      interleukin-1beta (IL-1beta) and high sensitive C-reactive protein (CRP) could be
      used as markers of tocolysis failure and adverse neonatal outcome in pregnancies
      with preterm labor (PL). METHODS: Forty-seven maternal blood samples taken
      because of PL at admission and delivery were analyzed. Control samples were taken
      from 20 gravidas with normal pregnancies. Differences in interleukins and CRP
      levels with or without chorioamnionitis, connatal infection or periventricular
      leukomalacia (PVL) were analyzed. Cut-off values were estimated for prediction of
      tocolysis failure and adverse neonatal outcome. RESULTS: All three parameters
      were significantly higher in patients delivering prematurely than in patients
      delivering at term. All three parameters were significantly higher with than
      without histologic chorioamnionitis (p < 0.001), with than without connatal
      infection (p < 0.01), with than without PVL (p < 0.01 for IL-6 and IL-1beta, p <
      0.05 for CRP), and in pregnancies with preterm premature rupture of membranes
      (PPROM) delivered within 48 hours compared to those more prolonged (p < 0.01).
      Choosing 50.9 pg/mL of IL-6 and a CRP of 19.7 as cut-offs in maternal blood
      admission concentrations for neonatal PVL, resulted in sensitivity of 81% and
      specificity of 91% and sensitivity of 91% and specificity of 81%, respectively.
      At respective maternal blood admission cut-off levels of 27.8 pg/mL of IL-6 and
      8.9 of CRP, both parameters were effective predictors of connatal infection.
      CONCLUSIONS: Maternal blood IL-6 and CRP could become useful in predicting
      tocolysis failure and intrauterine treat for the fetus.

PMID- 17437243
TI  - Fetal cardiac rhabdomyoma: a sheep or a wolf?
AB  - Rhabdomyoma is the most common primary cardiac tumor identified in utero and in
      infancy. Usually it has a benign course, which has prompted an expectant approach
      to its management. We report herein the cases of three patients who presented
      prenatally with cardiac rhabdomyomas. Only one of them had a benign course. The
      other two patients provided recognizable characteristics of rhabdomyomas with an
      unfavorable course and demonstrated that fetal rhabdomyomas can have a fatal
      outcome.

PMID- 17437244
TI  - Conjoined twins: historical perspective and report of a case.
AB  - In this article we review the historically important cases of conjoined twins
      (Biddenden Maids, Siamese twins, Blazek sisters) and contemporary knowledge
      regarding incidence, etiopathogenesis, antenatal diagnosis, antenatal management,
      and outcome of conjoined twins. We also present a case of male
      cephalothoracoomphalopagus, which is extremely rare.

PMID- 17437245
TI  - Tuberculous meningitis in pregnancy presenting as hyperemesis gravidarum.

PMID- 17437246
TI  - Understanding interactions of gastric inhibitory polypeptide (GIP) with its G
      protein coupled receptor through NMR and molecular modeling.
AB  - Gastric inhibitory polypeptide (GIP, or glucose-dependent insulinotropic
      polypeptide) is a 42-amino acid incretin hormone moderating glucose-induced
      insulin secretion. Antidiabetic therapy based on GIP holds great promise because
      of the fact that its insulinotropic action is highly dependent on the level of
      glucose, overcoming the sideeffects of hypoglycemia associated with the current
      therapy of Type 2 diabetes. The truncated peptide, GIP(1-30)NH2, has the same
      activity as the full length native peptide. We have studied the structure of
      GIP(1-30)NH2 and built a model of its G-protein coupled receptor (GPCR). The
      structure of GIP(1-30)NH2 in DMSO-d6 and H2O has been studied using 2D NMR (total
      correlation spectroscopy (TOCSY), nuclear overhauser effect spectroscopy (NOESY),
      double quantum filtered-COSY (DQF-COSY), 13C-heteronuclear single quantum
      correlation (HSQC) experiments, and its conformation built by MD simulations with
      the NMR data as constraints. The peptide in DMSO-d6 exhibits an alpha-helix
      between residues Ile12 and Lys30 with a discontinuity at residues Gln19 and
      Gln20. In H2O, the alpha-helix starts at Ile7, breaks off at Gln19, and then
      continues right through to Lys30. GIP(1-30)NH2 has all the structural features of
      peptides belonging to family B1 GPCRs, which are characterized by a coil at the N
      terminal and a long C-terminal alpha-helix with or without a break. A model of
      the seven transmembrane (TM) helices of the GIP receptor (GIPR) has been built on
      the principles of comparative protein modeling, using the crystal structure of
      bovine rhodopsin as a template. The N-terminal domain of GIPR has been
      constructed from the NMR structure of the N-terminal of corticoptropin releasing
      factor receptor (CRFR), a family B1 GCPR. The intra and extra cellular loops and
      the C-terminal have been modeled from fragments retrieved from the PDB. On the
      basis of the experimental data available for some members of family B1 GPCRs,
      four pairs of constraints between GIP(1-30)NH2 and its receptor were used in the
      FTDOCK program, to build the complete model of the GIP(1-30)NH2:GIPR complex. The
      model can rationalize the various experimental observations including the potency
      of the truncated GIP peptide. This work is the first complete model at the atomic
      level of GIP(1-30)NH2 and of the complex with its GPCR.

PMID- 17437247
TI  - Assessment of anthrax vaccination data in the Defense Medical Surveillance
      System, 1998-2004.
AB  - PURPOSE: Understanding the completeness and accuracy of U.S. military anthrax
      vaccination data is important to the design and interpretation of studies to
      assess the safety of anthrax vaccine. We estimated the agreement between
      electronically recorded anthrax vaccination data in the Defense Medical
      Surveillance System (DMSS) versus anthrax vaccination data abstracted from
      hardcopy medical charts in a representative sample of the U.S. military from 1998
      to 2004. METHODS: Medical chart abstractions were conducted at 28 military
      treatment facilities for 4201 personnel. Abstracted anthrax vaccination data for
      1817 personnel, representing 7400 anthrax vaccine doses, were compared with
      electronically captured data in the DMSS from 1998 to 2004. Sensitivity, positive
      predictive value (PPV), specificity and negative predictive value (NPV) were
      calculated using weighted analyses. RESULTS: Weighted person-level analysis
      revealed DMSS sensitivity = 93.8% (95%CI = 91.1, 95.8), specificity = 87.0%
      (79.0, 92.3), PPV = 85.6% (77.2, 91.3) and NPV = 94.5% (91.7, 96.4). Report of
      anthrax vaccination within a +/-7 days window in both medical chart and DMSS
      electronic data had a sensitivity of 88.3% (85.4, 90.7) and a PPV of 86.6% (84.9,
      88.2) in the vaccine dose-level analysis. CONCLUSIONS: These results support that
      anthrax vaccination data captured by the DMSS are adequate for post-marketing
      surveillance investigations in the U.S. military and are of comparable quality to
      data captured by other vaccine safety databases.

PMID- 17437248
TI  - The sequence TGAAKAVALVL from glyceraldehyde-3-phosphate dehydrogenase displays
      structural ambivalence and interconverts between alpha-helical and beta-hairpin
      conformations mediated by collapsed conformational states.
AB  - The peptide TGAAKAVALVL from glyceraldehyde-3-phosphate dehydrogenase adopts a
      helical conformation in the crystal structure and is a site for two hydrated
      helical segments, which are thought to be helical folding intermediates.
      Overlapping sequences of four to five residues from the peptide, sample both
      helical and strand conformations in known protein structures, which are
      dissimilar to glyceraldehyde-3-phosphate dehydrogenase suggesting that the
      peptide may have a structural ambivalence. Molecular dynamics simulations of the
      peptide sequence performed for a total simulation time of 1.2 micros, starting
      from the various initial conformations using GROMOS96 force field under NVT
      conditions, show that the peptide samples a large number of conformational forms
      with transitions from alpha-helix to beta-hairpin and vice versa. The peptide,
      therefore, displays a structural ambivalence. The mechanism from alpha-helix to
      beta-hairpin transition and vice versa reveals that the compact bends and turns
      conformational forms mediate such conformational transitions. These compact
      structures including helices and hairpins have similar hydrophobic radius of
      gyration (Rgh) values suggesting that similar hydrophobic interactions govern
      these conformational forms. The distribution of conformational energies is
      Gaussian with helix sampling lowest energy followed by the hairpins and coil. The
      lowest potential energy of the full helix may enable the peptide to take up
      helical conformation in the crystal structure of the glyceraldehyde-3-phosphate
      dehydrogenase, even though the peptide has a preference for hairpin too. The
      relevance of folding and unfolding events observed in our simulations to
      hydrophobic collapse model of protein folding are discussed.

PMID- 17437249
TI  - Interaction of S413-PV cell penetrating peptide with model membranes: relevance
      to peptide translocation across biological membranes.
AB  - Cell penetrating peptides (CPPs) have been successfully used to mediate the
      intracellular delivery of a wide variety of molecules of pharmacological interest
      both in vitro and in vivo, although the mechanisms by which the cellular uptake
      occurs remain unclear and controversial. Following our previous work
      demonstrating that the cellular uptake of the S4(13)-PV CPP occurs mainly through
      an endocytosis-independent mechanism, we performed a detailed biophysical
      characterization of the interaction of this peptide with model membranes. We
      demonstrate that the interactions of the S4(13)-PV peptide with membranes are
      essentially of electrostatic nature. As a consequence of its interaction with
      negatively charged model membranes, the S4(13)-PV peptide becomes buried into the
      lipid bilayer, which occurs concomitantly with significant peptide conformational
      changes that are consistent with the formation of a helical structure.
      Comparative studies using two related peptides demonstrate that the
      conformational changes and the extent of cell penetration are dependent on the
      peptide sequence, indicating that the helical structure acquired by the S4(13)-PV
      peptide is relevant for its nonendocytic uptake. Overall, our data suggest that
      the cellular uptake of the S4(13)-PV CPP is a consequence of its direct
      translocation through cell membranes, following conformational changes induced by
      peptide-membrane interactions.

PMID- 17437250
TI  - Preoperative but not postoperative systemic inflammatory response correlates with
      survival in colorectal cancer.
AB  - BACKGROUND: The aim of the present study was to evaluate the relationship between
      the preoperative and postoperative systemic inflammatory response and survival in
      patients undergoing potentially curative resection for colorectal cancer.
      METHODS: One hundred and eighty patients with colorectal cancer were studied.
      Circulating concentrations of C-reactive protein (CRP) were measured before
      surgery and in the immediate postoperative period. RESULTS: The peak in CRP
      concentration occurred on day 2 (P < 0.001). During the course of the study 59
      patients died, 30 from cancer and 29 from intercurrent disease. Day 2 CRP
      concentrations were dichotomized. In univariable analysis, advanced tumour node
      metastasis stage (P = 0.002), a raised preoperative CRP level (P < 0.001) and the
      presence of hypoalbuminaemia (P = 0.043) were associated with poorer cancer
      specific survival. CONCLUSION: Preoperative but not postoperative CRP
      concentrations are associated with poor tumour-specific survival in patients
      undergoing potentially curative resection for colorectal cancer.

PMID- 17437251
TI  - Unconditional efficient one-sided confidence limits for the odds ratio based on
      conditional likelihood.
AB  - We compare various one-sided confidence limits for the odds ratio in a 2 x 2
      table. The first group of limits relies on first-order asymptotic approximations
      and includes limits based on the (signed) likelihood ratio, score and Wald
      statistics. The second group of limits is based on the conditional tilted
      hypergeometric distribution, with and without mid-P correction. All these limits
      have poor unconditional coverage properties and so we apply the general
      transformation of Buehler (J. Am. Statist. Assoc. 1957; 52:482-493) to obtain
      limits which are unconditionally exact. The performance of these competing exact
      limits is assessed across a range of sample sizes and parameter values by looking
      at their mean size. The results indicate that Buehler limits generated from the
      conditional likelihood have the best performance, with a slight preference for
      the mid-P version. This confidence limit has not been proposed before and is
      recommended for general use, especially when the underlying probabilities are not
      extreme.

PMID- 17437252
TI  - Managing arable weeds for biodiversity.
AB  - As a result of the recent intensification of crop production, the abundance and
      diversity of UK arable weeds adapted to cultivated land have declined, with an
      associated reduction in farmland birds. A number of questions need to be
      addressed when considering how these declines can be reversed. Firstly, can the
      delivery of crop production and biodiversity be reconciled by spatially
      separating cropping from designated wildlife areas? A number of subsidised
      environmental schemes in the UK take this approach and are focused on
      establishing vegetation cover on uncropped land. However, because of the lack of
      regular disturbance in these habitats, they are dominated by perennials and they
      therefore have limited potential for promoting the recovery of annual weed
      populations. A number of farmland bird species also rely on the provision of
      resources in field centres, and it is therefore likely that the recovery of their
      populations will rely on weed management options targeted at the cropped areas of
      the field. This raises two further questions. Firstly, is it possible to identify
      beneficial weed species that are relatively poor competitors with the crop and
      also have biodiversity value? Secondly, are the tools available to manage these
      species at acceptable levels while controlling pernicious weeds? A number of
      approaches are being employed to answer these questions, including predicting
      yield loss from weed competition models and exploiting herbicide selectivity. The
      further development of these tools is crucial if farmer opposition to managing
      weeds in crops is to be overcome.

PMID- 17437253
TI  - Monitoring the efficacy and metabolism of phenylcarbamates in sugar beet and
      black nightshade by chlorophyll fluorescence parameters.
AB  - Desmedipham, phenmedipham and a 50% mixture of the two decreased the maximum
      quantum efficiency of photosystem II (F(v)/F(m)) and the relative changes at the
      J step (F(vj)) immediately after spraying in both sugar beet and black nightshade
      grown in the greenhouse. Sugar beet recovered more rapidly from phenmedipham and
      the mixture than from desmedipham. Desmedipham and the mixture irreversibly
      affected F(v)/F(m) and F(vj) in black nightshade at much lower doses than in
      sugar beet. Black nightshade recovered from phenmedipham injury at the highest
      dose in the first experiment (120 g AI ha(-1)) but not in the second experiment
      (500 g AI ha(-1)). The dry matter dose-response relationships and the energy
      pipeline presentation confirmed the same trend. There was a relatively good
      correlation between F(vj) taken 1 day after spraying and dry matter taken 2 or 3
      weeks after spraying. The differential speed of herbicide metabolism between weed
      and crop plays an important role in herbicide selectivity and can be studied by
      using appropriate chlorophyll a fluorescence parameters.

PMID- 17437254
TI  - Bayesian modelling of tuberculosis clustering from DNA fingerprint data.
AB  - A combination of continuous and categorical tests, none of which is a gold
      standard, is often available for classification of subject status in
      epidemiologic studies. For example, tuberculosis (TB) molecular epidemiology uses
      select mycobacterial DNA sequences to provide clues about which cases of active
      TB are likely clustered, implying recent transmission between these cases, versus
      reactivation of previously acquired infection. The proportion of recently
      transmitted cases is important to public health, as different control methods are
      implemented as transmission rates increase. Standard typing methods include
      IS6110 restriction fragment length polymorphism (IS6110 RFLP), but recently
      developed polymerase chain reaction based genotyping modalities, including
      mycobacterial interspersed repetitive unit-variable-number tandem repeat and
      spoligotyping provide quicker results. In addition, it has recently been
      suggested that results from IS6110 RFLP can be used to create a continuous
      measure of genetic relatedness, called the nearest genetic distance. Whichever
      method is used, estimation of cluster rates is rendered difficult by the lack of
      a gold standard method for classifying cases as clustered or not. Since many of
      these methods are relatively new, their properties have not been extensively
      investigated. Misclassification errors subsequently lead to sub-optimal
      estimation of risk factors for clustering. Here we show how Bayesian latent class
      models can be used in such situations, for example to simultaneously analyse
      Mycobacterium tuberculosis DNA data from all three of the above methods. Using
      the data collected at the Public Health Unit in Montreal, we estimate the
      proportion of clustered cases and the operating characteristics of each method
      using information from all three methods combined, including both continuous and
      dichotomous measures from IS6110 RFLP. A misclassification-adjusted regression
      model provides estimates of the effects of risk factors on the clustering
      probabilities. We also discuss how one must carefully interpret any inferences
      that arise from a combination of continuous and dichotomous tests.

PMID- 17437255
TI  - Effect of pyriproxyfen on developing stages and embryogenesis of California red
      scale (CRS), Aonidiella aurantii.
AB  - During the past decade, the insect growth regulator pyriproxyfen has been the
      most used insecticide for controlling the California red scale (CRS), Aonidiella
      aurantii (Maskell), an important pest in citrus groves worldwide. The aim of the
      present research was to develop bioassays for determining the effect of
      pyriproxyfen on developing stages and embryogenesis of CRS that can serve as
      baselines for monitoring resistance. Pyriproxyfen was very effective against
      first- and second-instar nymphs of a susceptible strain of CRS; 0.1 and 0.2 mg AI
      L(-1), resulting in 80 and 100% mortality of first-instar nymphs, and in 62.5 and
      91.7% mortality of second-instar nymphs respectively. According to probit
      analysis, the LC(50) and LC(90) values of pyriproxyfen for first-instar nymphs
      were 0.03 and 0.15 mg AI L(-1), and for second-instar nymphs they were 0.05 and
      0.25 mg AI L(-1) respectively. Pyriproxyfen was quite effective on first-instar
      nymphs of a CRS field strain originating from a citrus grove where two successive
      applications of the compound had been applied. Mortality rates were 86 and 100%
      at concentrations of 0.2 and 0.4 mg AI L(-1) respectively. Pyriproxyfen
      suppressed embryogenesis when CRS females were treated with pyriproxyfen. Young
      CRS females treated with 1.0 and 5.0 mg AI L(-1) pyriproxyfen produced 6.6 N(1)/F
      and 2.4 N(1)/F as compared with 10.9 N(1)/F in untreated control.

PMID- 17437256
TI  - Impact of a Turkish isolate and a plaque-purified variant of SpliNPV-B on larval
      stage development of Spodoptera littoralis (Lepidoptera: Noctuidae) Boisd.
AB  - Baculoviruses can alter the development and physiological status of their insect
      hosts. In the present study, two Spodoptera littoralis nucleopolyhedroviruses
      (SpliNPV-TR1 and SpliNPV-M2) were examined in terms of their effect on the stage
      development of S. littoralis at two doses/concentrations by inoculation of
      neonates or third instars. Both isolates had an acute pathological effect on
      neonates. However, larval development was prolonged (6-36 h) by either infection
      when neonates were infected. When third-instar larvae were inoculated, no
      mortality occurred until insects moulted to later stages. When the isolates were
      compared, more mortality occurred in the fifth instar with SpliNPV-M2 than with
      SpliNPV-TR1, whereas less mortality occurred in the sixth instar with SpliNPV-M2
      than with SpliNPV-TR1. However, none of the isolates demonstrated a dose effect.
      Larvae died at 108-198 h post-inoculation at all infections, and none of them
      pupated. Larval development was retarded (0-126 h) for each stage when third
      instar larvae were inoculated. Consequently, SpliNPV-M2 would be a more effective
      control agent than SpliNPV-TR1 for control of S. littoralis since it kills larvae
      at earlier developmental stages.

PMID- 17437257
TI  - Report of resistance to the neonicotinoid insecticide imidacloprid in
      Trialeurodes vaporariorum (Hemiptera: Aleyrodidae).
AB  - Susceptibilities of UK and mainland European samples of Trialeurodes vaporariorum
      (Westwood) to the neonicotinoid insecticide imidacloprid were investigated over a
      7 year period. All 24 strains collected between 1997 and 2003 showed similar
      baseline levels of susceptibility to that of a known susceptible laboratory
      strain when exposed to a diagnostic concentration (128 mg L(-1)) of formulated
      imidacloprid. Two samples collected during 2004, one from the UK and one from The
      Netherlands, demonstrated reduced susceptibility at this concentration. Using
      dose-response assays, the presence of resistant individuals was disclosed in both
      these strains; some individuals were unaffected at doses high enough to induce
      phytotoxic effects. This report represents the first confirmed cases of
      neonicotinoid resistance inducing control failures in T. vaporariorum, and
      highlights a need for careful vigilance to sustain the effectiveness of
      imidacloprid and related neonicotinoid insecticides.

PMID- 17437258
TI  - Integrated control of pests in tropical and subtropical sweet pepper production.
AB  - Sweet pepper is now grown, in tropical and subtropical areas, under the
      integrated pest management (IPM) tactic of 'physical barrier', whereas it was
      once grown primarily in open fields. This management tactic, when properly
      employed, has the advantage of eliminating many of the larger open-field pests,
      and has resulted in greatly increased pepper yields. However, certain other pest
      populations are exacerbated by this IPM tactic. This paper reviews the primary
      pests and current control tactics in sweet pepper.

PMID- 17437259
TI  - Novel treatment approaches for refractory anxiety disorders.
AB  - The Anxiety Disorders Association of America convened a conference of experts to
      address treatment-resistant anxiety disorders and review promising novel
      approaches to the treatment of refractory anxiety disorders. Workgroup leaders
      and other participants reviewed the literature and considered the presentations
      and discussions from the conference. Authors placed the emerging literature on
      new therapeutic approaches into clinical perspective and identified unmet needs
      and priority areas for future research. There is a relative paucity of efforts
      addressing inadequate response to anxiety disorder treatment. Systematic efforts
      to exhaust all therapeutic options and overcome barriers to effective treatment
      delivery are needed before patients can be considered treatment refractory.
      Cognitive behavioral therapy, especially in combination with pharmacotherapy,
      must be tailored to accommodate the effects of clinical context on treatment
      response. The literature on pharmacologic treatment of refractory anxiety
      disorders is small but growing and includes studies of augmentation strategies
      and non-traditional anxiolytics. Research efforts to discover new pharmacologic
      targets are focusing on neuronal systems that mediate responses to stress and
      fear. A number of clinical and basic science studies were proposed that would
      advance the research agenda and improve treatment of patients with anxiety
      disorders. Significant advances have been made in the development of
      psychotherapeutic and pharmacologic treatments for anxiety disorders.
      Unfortunately, many patients remain symptomatic and functionally impaired.
      Progress in the development of new treatments has great promise, but will only
      succeed through a concerted research effort that systematically evaluates
      potential areas of importance and properly uses scarce resources.

PMID- 17437260
TI  - Do mood disorders alter crying? A pilot investigation.
AB  - Clinical commentators widely interpret crying as a sign of depressed mood.
      However, there is virtually no empirical data on this topic, and the evidence
      that mood disorders alter crying is surprisingly weak. This study compared mood
      disordered patients to a nonpsychiatric reference group on the frequency,
      antecedents, and consequences of crying behavior using a well-validated
      questionnaire measure of crying. Forty-four outpatients diagnosed with three
      forms of mood pathology were age and gender matched to a reference group of 132
      participants sampled to be representative of the Dutch population. Both groups
      completed the Adult Crying Inventory, which provides estimates of the self
      reported frequency, antecedents, and consequences of crying behavior. Depression
      severity and psychiatric symptom severity data were also collected from patients.
      Compared with the reference group, patients with mood pathology reported
      increased cry proneness to negative antecedents. By contrast, patients and
      controls did not differ in reported cry proneness to positive antecedents.
      Patients reported less mood improvement after crying than did controls. Among
      male patients, but not female patients, depression severity was associated with
      increased crying proneness and increased crying frequency. This pilot
      investigation suggests that mood disorders increase the frequency of negative
      emotional crying, and may also alter the functions of this behavior. Mood
      disorders may influence male crying to a greater extent than female crying.
      Future directions designed to clarify the causal pathways between mood disorders
      and alterations in crying behavior are discussed.

PMID- 17437261
TI  - Determination of the enantiomeric excess of chiral carboxylic acids by 31P NMR
      with phosphorylated derivatizing agents from C2-symmetrical diamines containing
      the (S)-alpha-phenylethyl group.
AB  - The use of P(III) and P(V) organophosphorus derivatizing agents prepared from
      C(2) symmetrical (1R,2R)- and (1S,2S)-trans-N,N'-bis-[(S)-alpha-phenylethyl]
      cyclohexane-1,2-diamines 1 and 2, as well as (1R,2R)- and (1S,2S)-trans-N,N'-bis
      [(S)-alpha-phenylethyl]-4-cyclohexene-1,2-diamines 3 and 4 for the determination
      of enantiomeric composition of chiral carboxylic acids by (31)P NMR, is
      described.

PMID- 17437262
TI  - Enantioseparation of phenylglycinol in chiral-modified zeolite HY: a molecular
      simulation study.
AB  - A mechanism has been proposed for the separation of valinol enantiomers using a
      chiral-modified zeolite HY (i.e., zeolite HY containing (+)-(1R;2R)-hydrobenzoin)
      Molecular modeling of chiral-modified zeolite HY employed in enantioselective
      separation. Jirapongphan SS, Warzywoda J, Budil DE, Sacco A Jr. Chirality 2007;
      in press, which accurately predicted the experimentally measured
      enantioseparation. This methodology has been applied to predict the separation of
      an enantiomeric pair of phenylglycinol molecules (a precursor in the synthesis of
      HIV-1 protease inhibitors) using the modified zeolite HY as a CSP. Phenylglycinol
      and valinol molecules are similar in terms of the presence of polar (i.e., amine
      and hydroxyl) groups. These functional groups are important in the proposed
      chiral discrimination. Supercage-based docking simulations yielded an
      enantioselectivity of 1.3 with (+)-(S)-phenylglycinol molecule better retained in
      the zeolite. Also, the simulations predicted two binding modes that were the same
      as those in the valinol system. This suggests that specific structural features
      (i.e., number and type of polar groups), which generate the hypothesized binding
      modes, are required in an enantioseparation utilizing the chiral-modified zeolite
      HY.

PMID- 17437263
TI  - Molecular modeling of chiral-modified zeolite HY employed in enantioselective
      separation.
AB  - Insight into enantioselective separation utilizing chiral-modified zeolite HY
      could be useful in designing a chiral stationary phase for resolving
      pharmaceutical compounds. A model was employed to better understand the
      enantioseparation of valinol in zeolite HY that contains (+)-(1R;2R)-hydrobenzoin
      as a chiral modifier. This model incorporates the zeolite support and accounts
      for the flexible change. Results from grand canonical Monte Carlo and molecular
      dynamics simulations indicate that the associated diastereomeric complex consists
      of a single (+)-(1R;2R)-hydrobenzoin and a single valinol molecules located in
      the zeolite HY supercage. Supercage-based docking simulation predicted an
      enantioselectivity of 2.6 compared with that of 1.4 measured experimentally.
      Also, the supercage-based docking simulation demonstrated a single binding motif
      in the S complex, and two binding motifs in the R complex. The multiple binding
      modes in the R complex resulted in its lower stability. This is hypothesized to
      be the origin of the weaker binding between (-)-(R)-valinol and the chiral
      modifier, and explains why (+)-(R)-valinol is retained more in the chiral
      modified zeolite system studied.

PMID- 17437264
TI  - HPLC on chiral support with polarimetric detection: application to conglomerate
      discovery.
AB  - In conglomerates, each single crystal contains only one of the two possible
      enantiomeric forms--either dextrorotatory or levorotatory. The analysis of a
      single crystal by liquid chromatography on chiral support associated with
      chiroptical detection is a very efficient tool to reveal the occurrence of a
      conglomerate. In terms of rapidity and easiness, this method compares favorably
      with the classical methods used to show this occurrence. Two examples are
      provided.

PMID- 17437265
TI  - Wavelength shifts in solid-state circular dichroism spectra: a possible
      explanation.
AB  - We have devised an artificial sampling approach generating "absorption
      flattening" (AF) on the UV-Vis spectrum of a solution of a chiral compound: Tris
      (ethylendiamine)cobalt(III) chloride (Lambda-Co(en)(3)Cl(3)). We have observed a
      concomitant red shift of the CD maxima. Related CD and absorption spectra have
      been calculated from spectra recorded on diluted homogeneous solutions, thus
      monitoring the effect of AF on both types of data. Experimental data are in good
      agreement with calculated spectra. Simulations with suitable bandshapes show that
      the red shift of the CD spectrum is due to AF. On the basis of these results, we
      conclude that AF is an important cause of distortions in CD spectra for
      inhomogeneous samples. Plans to compensate or at least to take into account this
      effect are presented.

PMID- 17437268
TI  - Age-period-cohort projections of breast cancer incidence in a rapidly
      transitioning Chinese population.
AB  - Breast cancer incidence should be assessed separately in different populations,
      as it differs substantially between Chinese and Caucasian women, and more
      generally in developing versus developed populations. Estimation of future trends
      is important for public health planning. On the basis of the recent breast cancer
      incidence trends, we projected future disease rates in the rapidly transitioning
      Chinese population of Hong Kong. We used local data on breast cancer incidence
      and mid-year population figures for the years 1974-2003. We fitted Poisson age
      period-cohort models with autoregressive priors on the age, period and cohort
      effects, and used projections of these effects to forecast future incidence to
      2018. We found that age-standardized breast cancer incidence would continue to
      rise by approximately 1.1% per annum over the next 15 years, from 45.9 cases in
      1999-2003 to 54.3 per 100,000 (95% credible interval: 50.9, 58.4) in 2014-2018.
      Recent secular incidence increases can be attributed to both ageing and
      intergenerational effects beginning with the postwar baby boomers, whereas there
      is no evidence for important changes by time period. There does not appear to be
      differential cohort-related risk for pre- vs. postmenopausal disease. Unlike most
      other cancers, breast cancer risk in local women would continue to increase in
      the short to medium term, at a similar rate of increase compared with historical
      trends. This could most likely be attributed to Hong Kong's socioeconomic
      developmental history and continuing adoption of westernized lifestyle changes.

PMID- 17437269
TI  - Targeted delivery of doxorubicin to the rat brain at therapeutic levels using MRI
      guided focused ultrasound.
AB  - The clinical application of chemotherapy to brain tumors has been severely
      limited because antitumor agents are typically unable to penetrate an intact
      blood-brain barrier (BBB). Although doxorubicin (DOX) has been named as a strong
      candidate for chemotherapy of the central nervous system (CNS), the BBB often
      prevents cytotoxic levels from being achieved. In this study, we demonstrate a
      noninvasive method for the targeted delivery of DOX through the BBB, such that
      drug levels shown to be therapeutic in human tumors are achieved in the normal
      rat brain. Using MRI-guided focused ultrasound with preformed microbubbles
      (Optison) to locally disrupt the BBB and systemic administration of DOX, we
      achieved DOX concentrations of 886 +/- 327 ng/g tissue in the brain with minimal
      tissue effects. Tissue DOX concentrations of up to 5,366 +/- 659 ng/g tissue were
      achieved with higher Optison doses, but with more significant tissue damage. In
      contrast, DOX accumulation in nontargeted contralateral brain tissue remained
      significantly lower for all paired samples (p < 0.001). These results suggest
      that targeted delivery by focused ultrasound may render DOX chemotherapy a viable
      treatment option against CNS tumors, despite previous accessibility limitations.
      In addition, MRI signal enhancement in the sonicated region correlated strongly
      with tissue DOX concentration (r = 0.87), suggesting that contrast-enhanced MRI
      could perhaps indicate drug penetration during image-guided interventions. Our
      technique using MRI-guided focused ultrasound to achieve therapeutic levels of
      DOX in the brain offers a large step forward in the use of chemotherapy to treat
      patients with CNS malignancies.

PMID- 17437270
TI  - Inhibition of breast tumor growth and angiogenesis by a medicinal herb: Ocimum
      gratissimum.
AB  - Ocimum sp. is a traditionally used medicinal herb, which shows anti-oxidant, anti
      carcinogenic, radio-protective and free radical scavenging properties. So far no
      detailed studies have been reported on its effects on human cancers. Thus, we
      analyzed its effects on human breast cancer utilizing in vitro and in vivo
      methodologies. Aqueous extracts were prepared from the mature leaves of Ocimum
      gratissimum (OG) cultivated devoid of pesticides. Tumor progression and
      angiogenesis related processes like chemotaxis, proliferation, apoptosis, 3D
      growth and morphogenesis, angiogenesis and tumor growth were studied in the
      presence or absence of the extract, and in some experiments a comparison was made
      with purified commercially available eugenol, apigenin and ursolic acid. Aqueous
      OG leaf extract inhibits proliferation, migration, anchorage independent growth,
      3D growth and morphogenesis and induction of COX-2 protein in breast cancer
      cells. A comparative analysis with eugenol, apigenin and ursolic acid showed that
      the inhibitory effects on chemotaxis and 3D morphogenesis of breast cancer cells
      were specific to OG extract. In addition, OG extracts reduced tumor size and
      neoangiogenesis in a MCF10 DCIS.com xenograft model of human DCIS. This is the
      first detailed report showing that OG leaf extract may be of value as a breast
      cancer preventive and therapeutic agent and might be considered as additional
      additive in the arsenal of components aimed at combating breast cancer
      progression and metastasis.

PMID- 17437272
TI  - Cervical screening by visual inspection, HPV testing, liquid-based and
      conventional cytology in Amazonian Peru.
AB  - Cervical cancer is an important public health problem in many developing
      countries, where cytology screening has been ineffective. We compared four tests
      to identify the most appropriate for screening in countries with limited
      resources. Nineteen midwives screened 5,435 women with visual inspection (VIA)
      and collected cervical samples for HPV testing, liquid-based cytology (LBC) and
      conventional cytology (CC). If VIA was positive, a doctor performed magnified
      VIA. CC was read locally, LBC was read in Lima and HPV testing was done in
      London. Women with a positive screening test were offered colposcopy or
      cryotherapy (with biopsy). Inadequacy rates were 5% and 11% for LBC and CC
      respectively, and less than 0.1% for VIA and HPV. One thousand eight hundred
      eighty-one women (84% of 2,236) accepted colposcopy/cryotherapy: 79 had carcinoma
      in situ or cancer (CIS+), 27 had severe- and 42 moderate-dysplasia on histology.
      We estimated a further 6.5 cases of CIS+ in women without a biopsy. Sensitivity
      for CIS+ (specificity for less than moderate dysplasia) was 41.2% (76.7%) for
      VIA, 95.8% (89.3%) for HPV, 80.3% (83.7%) for LBC, and 42.5% (98.7%) for CC.
      Sensitivities for moderate dysplasia or worse were better for VIA (54.9%) and
      less favourable for HPV and cytology. In this setting, VIA and CC missed the
      majority of high-grade disease. Overall, HPV testing performed best. VIA gives
      immediate results, but will require investment in regular training and
      supervision. Further work is needed to determine whether screened-positive women
      should all be treated or triaged with a more specific test.

PMID- 17437271
TI  - Prostaglandin F(2alpha) stimulates motility and invasion in colorectal tumor
      cells.
AB  - Increased expression of cyclooxygenase-2 (COX-2) and subsequent prostaglandin
      production is an important event in several human malignancies, including
      colorectal cancer. COX-2 mediated prostanoid synthesis has been shown to play a
      key role in tumor progression with prostaglandin E(2) (PGE(2)) being shown to
      promote tumor growth, invasion and angiogenesis. The role of the other
      prostaglandins produced by COX-2 in tumors remains poorly understood. We have
      shown that colorectal tumor cells produce prostaglandin F(2alpha) (PGF(2alpha))
      and provide evidence that PGF(2alpha) may play an important role in colorectal
      tumorigenesis. Our data show that PGF(2alpha) is secreted by both colorectal
      adenoma and carcinoma-derived cell lines at levels in excess of those detected
      for PGE(2). These cell lines were also found to express the PGF(2alpha) receptor
      (FP) indicating potential autocrine effects of PGF(2alpha). This finding is
      further supported by an in vivo immunohistochemical study of FP expression in
      resected colon tissue. These data show epithelial expression of FP in normal
      colorectal mucosa and also in colorectal adenomas and carcinomas. We compared the
      relative abilities of PGF(2alpha) and PGE(2) to induce cell motility in vitro in
      colorectal tumor cell lines and show the first evidence of prostaglandin-induced
      cell motility in colorectal adenoma cell lines. PGF(2alpha) induced cell motility
      with equivalent potency to PGE(2) in all the cell lines tested and was also shown
      to increase the invasion of carcinoma-derived cells into reconstituted basement
      membrane. These data show that PGF(2alpha) may play an important role in the
      malignant progression of colorectal tumors.

PMID- 17437273
TI  - Risk of human T-lymphotropic virus type I-associated diseases in Jamaica with
      common HLA types.
AB  - Human T-lymphotropic virus-I (HTLV-I) causes adult T-cell leukemia/lymphoma (ATL)
      and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We
      postulated a higher disease risk for people with common human leukocyte antigen
      (HLA) types, due to a narrower immune response against viral or neoplastic
      antigens, compared to people with uncommon types. HLA class-I (A,B) and class-II
      (DRB1, DQB1) allele and haplotype frequencies in 56 ATL patients, 59 HAM/TSP
      patients and 190 population-based, asymptomatic HTLV-I-infected carriers were
      compared by logistic regression overall (score test) and with odds ratios (ORs)
      for common types (prevalence >50% of asymptomatic carriers) and by prevalence
      quartile. HTLV-I proviral load between asymptomatic carriers with common versus
      uncommon types was compared by t-test. ATL differed from asymptomatic carriers in
      overall DQB1 allele and class-I haplotype frequencies (p </=</= 0.04). ATL risk
      was increased significantly with common HLA-B (OR 2.25, 95% CI 1.19-4.25) and
      DRB1 (OR 2.11, 95% CI 1.13-3.40) alleles. Higher prevalence HLA-B alleles were
      associated with higher ATL risk (OR 1.14 per quartile, p(trend) = 0.02).
      Asymptomatic carriers with common HLA-B alleles had marginally higher HTLV-I
      proviral load (p = 0.057). HAM/TSP risk did not differ consistently with common
      HLA types. Thus, ATL risk, but not HAM/TSP risk, was increased with higher
      prevalence HLA-B alleles. Perhaps breadth of cellular immunity affects risk of
      this viral leukemia/lymphoma.

PMID- 17437274
TI  - Dietary patterns and risk of laryngeal cancer: an exploratory factor analysis in
      Uruguayan men.
AB  - Laryngeal carcinoma is a common malignancy among Uruguayan men. A number of case
      control and prospective studies have studied the role of diet in this malignancy.
      To our knowledge, this is the first study that has explored broad dietary
      patterns by factor (principal components) analysis. The results of this study
      retained 6 dietary patterns. Pattern 5 (drinker) was directly associated with
      risk of laryngeal carcinoma (OR 3.8, 95% CI 1.9-7.5), whereas the Pattern 2
      (healthy) was protective (OR 0.6, 95% CI 0.3-1.2). Finally, the Pattern 6
      (western) displayed a significant increase in risk of 3.2 (95% CI 1.6-6.2). Most
      dietary patterns were associated with supraglottic cancer, supporting a possible
      etiological difference between supraglottic and glottic carcinomas. This study
      also suggests that the analysis of dietary patterns might be a useful approach
      for investigating nutritional factors implicated in laryngeal carcinogenesis.

PMID- 17437275
TI  - Novel mutations in the ZEB1 gene identified in Czech and British patients with
      posterior polymorphous corneal dystrophy.
AB  - We describe the search for mutations in six unrelated Czech and four unrelated
      British families with posterior polymorphous corneal dystrophy (PPCD); a
      relatively rare eye disorder. Coding exons and intron/exon boundaries of all
      three genes (VSX1, COL8A2, and ZEB1/TCF8) previously reported to be implicated in
      the pathogenesis of this disorder were screened by DNA sequencing. Four novel
      pathogenic mutations were identified in four families; two deletions, one
      nonsense, and one duplication within exon 7 in the ZEB1 gene located at 10p11.2.
      We also genotyped the Czech patients to test for a founder haplotype and lack of
      disease segregation with the 20p11.2 locus we previously described. Although a
      systematic clinical examination was not performed, our investigation does not
      support an association between ZEB1 changes and self reported non-ocular
      anomalies. In the remaining six families no disease causing mutations were
      identified thereby indicating that as yet unidentified gene(s) are likely to be
      responsible for PPCD.

PMID- 17437276
TI  - Aberrant splicing is a common mutational mechanism in MKS1, a key player in
      Meckel-Gruber syndrome.
AB  - Meckel-Gruber syndrome (MKS) is an autosomal recessive, usually lethal
      multisystemic disorder characterized by early developmental anomalies of the
      central nervous system, cystic kidney dysplasia, hepatobiliary ductal plate
      malformation, and postaxial polydactyly. Three MKS loci have been mapped and
      recently, two genes were identified: MKS1 on 17q22 in Caucasian kindreds and MKS3
      on 8q22 in Omani and Pakistani families, putting MKS on the growing list of
      ciliary disorders ("ciliopathies"). We performed linkage analysis for MKS1-3 in
      14 consanguineous and/or multiplex families of different ethnic origins with
      histologic diagnosis and at least three classic MKS manifestations in each
      kindred. Unexpectedly, only five families were linked to any of the known MKS
      loci, clearly indicating further locus heterogeneity. All five families showed
      homozygosity for MKS1 and, intriguingly, were of non-Caucasian origin. MKS1
      sequencing revealed no mutation in two of these pedigrees, whereas different,
      novel splicing defects were identified in the three other families and an
      additional sporadic German patient. Given that all of our mutations and two of
      the in total four known MKS1 changes cause aberrant splicing (while the other two
      known mutations were frameshift mutations), we hypothesize that splicing defects
      are a crucial mutational mechanism in MKS1 which apparently is one of the main
      loci and key players in MKS. Our results indicate that MKS1 mutations are not
      restricted to the Caucasian gene pool and suggest further genetic heterogeneity
      for MKS. Overall, our data have immediate implications for genetic counselling
      and testing approaches in MKS.

PMID- 17437277
TI  - Missense and silent mutations in COL2A1 result in Stickler syndrome but via
      different molecular mechanisms.
AB  - Stickler syndrome due to mutations in COL2A1 is usually the result of premature
      termination codons and nonsense mediated decay resulting in haploinsufficiency of
      type II collagen. Here we present two missense mutations and one apparently
      silent mutation that each result in Stickler syndrome, but via different
      molecular mechanisms. One alters the translation initiating ATG codon. The second
      mutation is a unique glycine substitution in the minor collagen helix of the
      procollagen. To our knowledge a glycine substitution has not previously been
      reported in this region of fibrillar procollagens. The third mutation appears to
      be a silent change altering a GGC codon to GGT both for glycine, but use of a
      splicing reporter assay demonstrates that it results in missplicing and a shift
      in the reading frame.

PMID- 17437278
TI  - One hit, two hits, three hits, more? Genomic changes in the development of
      retinoblastoma.
AB  - The childhood eye cancer retinoblastoma is initiated by the loss of both alleles
      of the prototypic tumor suppressor gene, RB1. However, a large number of
      cytogenetic and comparative genomic hybridization (CGH) studies have shown that
      these M1 and M2 mutational events--although necessary for initiation--are not the
      only genomic changes in retinoblastoma. Some of these subsequent changes, which
      we have termed M3 to Mn, are likely crucial for tumor progression not only in
      retinoblastoma but also in other cancers. Moreover, genes showing genomic change
      in cancer are more stable markers and, therefore, possible therapeutic targets
      than genes simply differentially expressed. In this review, we provide the first
      comprehensive summary of the genomic evidence implicating gain of 1q, 2p, 6p, and
      13q, and loss of 16q in retinoblastoma oncogenesis, including karyotype, CGH, and
      microarray CGH data. We discuss the search for candidate oncogenes and tumor
      suppressor genes within these regions, including the candidates (KIF14, MDM4,
      MYCN, E2F3, DEK, CDH11, and others), plus associations between genomic changes
      and clinical parameters. We also review studies of other regions of the
      retinoblastoma genome, the epigenetic changes of aberrant methylation of MGMT,
      RASSF1A, CASP8, and MLH1, and the roles microRNAs might play in this cancer.
      Although many candidate genes have yet to be functionally validated in
      retinoblastoma, work in this field lays out a molecular cytogenetic pathway of
      retinoblastoma development. Candidate cancer genes carry diagnostic, prognostic,
      and therapeutic implications beyond retinoblastoma.

PMID- 17437280
TI  - Women with Saethre-Chotzen syndrome are at increased risk of breast cancer.
AB  - The Saethre-Chotzen syndrome is an autosomal, dominantly inherited
      craniosynostosis caused by mutations in the basic helix-loop-helix transcription
      factor gene TWIST1. This syndrome has hitherto not been associated with an
      increased risk of cancer. However, recent studies, using a murine breast tumor
      model, have shown that Twist may act as a key regulator of metastasis and that
      the gene is overexpressed in subsets of sporadic human breast cancers. Here, we
      report a novel association between the Saethre-Chotzen syndrome and breast
      cancer. In 15 Swedish Saethre-Chotzen families, 15 of 29 (52%) women carriers
      over the age of 25 had developed breast cancer. At least four patients developed
      breast cancer before 40 years of age, and five between 40 and 50 years of age.
      The observed cases with breast cancer (n = 15) are significantly higher than
      expected (n = 0.89), which gives a standardized incidence ratio (SIR) of 16.80
      (95% CI 1.54-32.06). Our finding of a high frequency of breast cancer in women
      with the Saethre-Chotzen syndrome identifies breast cancer as an important and
      previously unrecognized symptom characteristic of this syndrome. The results
      strongly suggest that women carriers of this syndrome would benefit from genetic
      counseling and enrolment in surveillance programs including yearly mammography.
      Our results also indicate that the TWIST1 gene may be a novel breast cancer
      susceptibility gene. Additional studies are, however, necessary to reveal the
      mechanism by which TWIST1 may predispose to early onset breast cancer in Saethre
      Chotzen patients.

PMID- 17437281
TI  - CRTC1/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary
      and thyroid glands and Warthin's tumors: implications for histogenesis and
      biologic behavior.
AB  - We analyzed 55 primary salivary gland tumors including 22 mucoepidermoid
      carcinomas (MECs) to determine the association of MECT1/TORC1/CRTC1-MAML2 fusion
      transcript to tumor types, level of MEC differentiation and clinicopathologic
      parameters. Our primary salivary gland tumors were composed of 22 MECs, 11
      Warthin's tumors, 10 adenoid cystic carcinomas, two basaloid carcinomas, five
      salivary duct carcinomas, and five adenocarcinomas, not otherwise specified. We
      also included, for the first time, three primary MECs of the thyroid gland. We
      used nested RT-PCR and subsequent sequencing techniques for detection and
      verification of the fusion transcript in fresh and archival specimens. Eighteen
      (81%) of the 22 primary salivary and one of the three thyroid glands with MEC
      were positive for the fusion transcript. The transcript was detected equally in
      low, intermediate and high grade as well as low and high stage MECs. Significant
      correlation between fusion negative tumors and distant metastasis was noted (P =
      0.005). Four (36%) of the 11 Warthin's tumors were also positive for the
      transcript. None of the 22 primary non-MEC gland salivary carcinomas were
      positive for the transcript. We conclude that the CRTC1/MAML2 transcript may be
      detected in both low and high grade MEC, that fusion negative tumors may define a
      subset of biologically aggressive MEC's tumors, that the fusion is present in
      primary MECs of the thyroid gland and is also detectable in Warthin's tumor, and
      that a subset of MECs can be targeted for therapeutic intervention.

PMID- 17437282
TI  - Fronto-striatal dysfunction and potential compensatory mechanisms in male
      adolescents with fragile X syndrome.
AB  - Response inhibition is an important facet of executive function. Fragile X
      syndrome (FraX), with a known genetic etiology (fragile X mental retardation-1
      (FMR1) mutation) and deficits in response inhibition, may be an ideal condition
      for elucidating interactions among gene-brain-behavior relationships. Functional
      magnetic resonance imaging (fMRI) studies have shown evidence of aberrant neural
      activity when individuals with FraX perform executive function tasks, though the
      specific nature of this altered activity or possible compensatory processes has
      yet to be elucidated. To address this question, we examined brain activation
      patterns using fMRI during a go/nogo task in adolescent males with FraX and in
      controls. The critical comparison was made between FraX individuals and age,
      gender, and intelligent quotient (IQ)-matched developmentally delayed controls;
      in addition to a control group of age and gender-matched typically developing
      individuals. The FraX group showed reduced activation in the right ventrolateral
      prefrontal cortex (VLPFC) and right caudate head, and increased contralateral
      (left) VLPFC activation compared with both control groups. Individuals with FraX,
      but not controls, showed a significant positive correlation between task
      performance and activation in the left VLPFC. This potential compensatory
      activation was predicted by the interaction between FMR1 protein (FMRP) levels
      and right striatal dysfunction. These results suggest that right fronto-striatal
      dysfunction is likely an identifiable neuro-phenotypic feature of FraX and that
      activation of the left VLPFC during successful response inhibition may reflect
      compensatory processes. We further show that these putative compensatory
      processes can be predicted by a complex interaction between genetic risk and
      neural function.

PMID- 17437283
TI  - Magnetic resonance imaging as a tool for in vivo and ex vivo anatomical
      phenotyping in experimental genetic models.
AB  - This article describes a suite of computational approaches suitable for deriving
      various quantitative phenotypes from structural magnetic resonance (MR) images
      obtained in rodents and used subsequently in genetic studies of complex traits.
      We begin by introducing the basic principles of genetic studies of complex traits
      in experimental models. We then illustrate the use of MR-based computational
      anatomy in vivo and ex vivo, and in combination with histology. This work was
      carried out in two inbred strains of rats, namely spontaneously hypertensive rats
      and Brown Norway rats; these are parental strains of the only existing panel of
      recombinant inbred strains of rats. The rats were scanned in vivo at two time
      points (at 8 and 12 weeks of age) and ex vivo (at 12 weeks of age). We describe
      between-strain differences and across-time changes in brain and kidney volumes,
      as well as regional variations in brain structure using surface- and deformation
      based approaches. We conclude by discussing the power of the population-based
      computational analysis of MR images, and their fusion with histology, in studies
      of complex traits.

PMID- 17437285
TI  - Heritability of brain volume, surface area and shape: an MRI study in an extended
      pedigree of baboons.
AB  - To evaluate baboons (Papio hamadryas) as a primate model for the study of the
      genetic control of brain size and internal structure, we performed high
      resolution (<500 microm) magnetic resonance imaging on 109 pedigreed baboons.
      Quantitative genetic analysis of these MR images using a variance components
      approach indicates that native (untransformed) brain volume exhibits significant
      heritability among these baboons (h(2) = 0.52, P = 0.0049), with age and sex also
      accounting for substantial variation. Using global spatial normalization, we
      transformed all images to a standard population-specific reference, and
      recalculated the heritability of brain volume. The transformed images generated
      heritability estimates of h(2) = 0.82 (P = 0.00022) for total brain volume, h(2)
      = 0.86 (P = 0.0006) for cerebral volume, h(2) = 0.73 (P = 0.0069) for exposed
      surface area of the cerebrum and h(2) = 0.67 (P = 0.01) for gray matter volume.
      Regional differences in the genetic effects on brain structure were calculated
      using a voxel-based morphometry (VBM) approach. This analysis of regional
      variation shows that some areas of motor cortex and the superior temporal gyrus
      show relatively high heritability while other regions (e.g. superior parietal
      cortex) exhibit lower heritability. The general pattern of regional differences
      is similar to that observed in previous studies of humans. The present study
      demonstrates that there is substantial genetic variation underlying individual
      variation in brain size and structure among Papio baboons, and that broad
      patterns of genetic influence on variation in brain structure may be similar in
      baboons and humans.

PMID- 17437286
TI  - Depressive symptoms and SSRI use in pediatric oncology patients.
AB  - This review of depressive symptoms in pediatric cancer patients describes the
      challenge of recognizing depression in this group, prevalence, risk factors, and
      treatment, primarily with the selective serotonin reuptake inhibitors (SSRIs).
      Pediatric oncologists prescribe SSRIs, but there is limited data regarding their
      use in this setting. Adverse effects, pharmacokinetics and metabolism of SSRIs
      are reviewed to provide a reference for physicians and inform choices for SSRI
      prescription. Ongoing research includes incorporation of routine screening
      measures for depression and future studies might focus on physician recognition
      and prospectively evaluating treatment for children with cancer and depressive
      symptoms.

PMID- 17437284
TI  - Cortical mapping of genotype-phenotype relationships in schizophrenia.
AB  - Although schizophrenia is highly heritable, the search for susceptibility genes
      has been challenging. The "endophenotype" approach is an alternative method for
      measuring phenotypic variation that may make it easier to identify susceptibility
      genes in the context of complexly inherited traits. Neuroimaging methods in
      particular offer a powerful way to bridge the neurobiology of genes and behavior.
      Such investigations may be further empowered by complementary strategies
      involving chromosomal abnormalities associated with schizophrenia, which can help
      to localize causative genes and better understand the genetic complexity of the
      illness. Here, we illustrate our use of these convergent approaches, with a focus
      on neuroimaging studies using novel computational brain mapping algorithms, to
      investigate genetic influences on brain structure in the development of
      psychosis. These studies provide compelling evidence that specific genetic loci
      suspected to predispose to schizophrenia may affect quantitative variation in
      neural indicators underlying the neurobehavioral phenotype, and illustrate how
      genetic-neuroimaging paradigms can improve our understanding of the pathogenesis
      of this highly disabling mental illness.

PMID- 17437287
TI  - Evidence-based guidelines for following stage 1 seminoma.
AB  - BACKGROUND: The authors developed evidence-based guidelines for a follow-up
      schedule after orchiectomy for stage 1 seminoma. Required investigations,
      frequency of assessment, overall duration of follow-up, and management strategies
      were identified. METHODS: A systematic review of the literature was performed of
      prospective studies in stage 1 seminoma. Studies published after 1980 were
      considered eligible for inclusion. Data extracted included relapse-free rates,
      number of patients at risk, and relapse locations. Five strategies were
      identified: Surveillance, Extended-Field Radiotherapy, Para-aortic Radiotherapy,
      and either 1 or 2 cycles of Carboplatin Chemotherapy. For each strategy, Kaplan
      Meier relapse-free estimates were used to calculate weighted-mean cumulative
      hazards of relapse over time. These were used to calculate semiannual weighted
      mean relapse hazards. RESULTS: Seventeen prospective studies with a total of 5561
      patients were identified. Actuarial data on relapse was available in 5013 (90.1%)
      patients, and 92.9% of all relapses had location data reported. Annual hazard
      rates for relapse were determined. CONCLUSIONS: Evidence-based recommendations
      for follow-up frequency based on risk of relapse were formulated. The authors
      suggested 3 times per year when the risk is >5%, 2 times per year when the risk
      is 1% to 5%, and annually until the risk is <0.3%. Investigations should reflect
      location(s) at risk of relapse and include computed tomography of the abdomen and
      pelvis for surveillance and adjuvant carboplatin, whereas for para-aortic
      radiotherapy, pelvic computed tomography alone is required. These recommendations
      offer the possibility of maximal patient convenience and optimal healthcare
      resource allocation without compromising disease control.

PMID- 17437288
TI  - Statistical methods for describing developmental milestones with censored data:
      effects of birth weight status and sex in neonatal pigtailed macaques.
AB  - Neurobehavioral tests are used to assess early neonatal behavioral functioning
      and detect effects of prenatal and perinatal events. However, common measurement
      and data collection methods create specific data features requiring thoughtful
      statistical analysis. Assessment response measurements are often ordinal scaled,
      not interval scaled; the magnitude of the physical response may not directly
      correlate with the underlying state of developmental maturity; and a subject's
      assessment record may be censored. Censoring occurs when the milestone is
      exhibited at the first test (left censoring), when the milestone is not exhibited
      before the end of the study (right censoring), or when the exact age of attaining
      the milestone is uncertain due to irregularly spaced test sessions or missing
      data (interval censoring). Such milestone data is best analyzed using survival
      analysis methods. Two methods are contrasted: the non-parametric Kaplan-Meier
      estimator and the fully parametric interval censored regression. The methods
      represent the spectrum of survival analyses in terms of parametric assumptions,
      ability to handle simultaneous testing of multiple predictors, and accommodation
      of different types of censoring. Both methods were used to assess birth weight
      status and sex effects on 14 separate test items from assessments on 255 healthy
      pigtailed macaques. The methods gave almost identical results. Compared to the
      normal birth weight group, the low birth weight group had significantly delayed
      development on all but one test item. Within the low birth weight group, males
      had significantly delayed development for some responses relative to females.

PMID- 17437289
TI  - Graft versus leukemia effect against juvenile myelomonocytic leukemia after
      unrelated cord blood transplantation.
AB  - A 13-month-old female underwent unrelated cord blood transplantation (CBT) for
      juvenile myelomonocytic leukemia (JMML). In spite of progression of the disease
      after a conditioning regimen with high-dose chemotherapy, a complete remission
      was induced in concordance with development of acute GVHD after reduction of the
      immunosupressant. She has been in complete remission for 1 year after
      transplantation. This case illustrates that CBT can provide a potent graft versus
      leukemia (GVL) effect against JMML.

PMID- 17437290
TI  - Presentation of acute promyelocytic leukemia as granulocytic sarcoma.
AB  - Granulocytic sarcoma (GS) is a localized tumor composed of immature myeloid
      cells. This extramedullary tumor can present before, concurrent with or after the
      diagnosis of acute myeloid leukemia. GS is extremely uncommon in acute
      promyelocytic leukemia (APL). As a proportion of patients never develop systemic
      disease, correct and timely diagnosis may be rather difficult, but is a
      prerequisite for optimal outcome. GS should be considered in the differential
      diagnosis of children with unusual bone lesions. We describe a patient with GS
      who presented with symptoms mimicking osteomyelytis or rheumatoid disease.

PMID- 17437291
TI  - Dyspnea as the first manifestation of primary pancreatic lymphoma.

PMID- 17437292
TI  - Mouse behavioral mutants have neuroimaging abnormalities.
AB  - Impaired cognitive, memory, or motor performance is a distinguishing
      characteristic of neurological diseases. Although these symptoms are frequently
      the most evident in human patients, additional markers of disease are critical
      for proper diagnosis and staging. Noninvasive neuroimaging methods have become
      essential in this capacity and provide means of evaluating disease and tracking
      progression. These imaging methods are also becoming available to scientists in
      the research laboratory for assessment of animal models of neurological disease.
      Imaging in mouse models of neurological disease is of particular interest, owing
      to the availability of inbred strains and genetic manipulation tools that permit
      detailed investigation of the roles of various genes and gene products in disease
      pathogenesis. However, the relative prevalence of neuroimaging abnormalities in
      mice exhibiting neurological symptoms has not been reported. This prevalence has
      both theoretical and practical value because it is influenced by both the
      sensitivity of macroscopic anatomical measures to underlying genetic and disease
      processes and by the efficiency of neuroimaging in detecting and characterizing
      these effects. In this paper, we describe a meta-analysis of studies involving
      behavioral mouse mutants at our laboratory. In summary, we have evaluated 15
      different mutant genotypes, of which 13 showed abnormal neuroimaging findings.
      This indicates a surprisingly high prevalence of neuroimaging abnormalities (87%)
      and suggests that disease processes affecting behavior generally alter
      neuroanatomy as well. As a consequence, neuroimaging provides a highly sensitive
      marker of neurological disease in mice exhibiting abnormal behavior.

PMID- 17437293
TI  - Individual variation in neural correlates of sadness in children: a twin fMRI
      study.
AB  - Functional neuroimaging studies show substantial individual variation in brain
      activation accompanying the experience of emotion, including sadness. Here we
      used functional magnetic resonance imaging (fMRI) in 104 pairs of 8-year-old
      twins (47 MZ, 57 DZ) to assess genetic-environmental contributions to individual
      differences in neural activation in two prefrontal cortex (PFC) areas previously
      shown to be involved in sadness. No genetic effects were found for any area,
      individual environmental factors entirely accounting for individual variation in
      brain activation related to sadness. Sadness being the prevailing mood in
      depression, these findings may be of relevance to the etiology of childhood
      depressive disorders.

PMID- 17437294
TI  - Functional organization of human visual cortex in occipital polymicrogyria.
AB  - Polymicrogyrias (PMG) are cortical malformations resulting from developmental
      abnormalities. In animal models PMG has been associated with abnormal anatomy,
      function, and organization. The purpose of this study was to describe the
      function and organization of human polymicrogyric cortex using functional
      magnetic resonance imaging. Three patients with epilepsy and bilateral
      parasagittal occipital polymicrogyri were studied. They all had normal vision as
      tested by Humphrey visual field perimetry. The functional organization of the
      visual cortex was reconstructed using phase-encoded retinotopic mapping analysis.
      This method sequentially stimulates each point in the visual field along the axes
      of a polar-coordinate system, thereby reconstructing the representation of the
      visual field on the cortex. We found normal cortical responses and organization
      of early visual areas (V1, V2, and V3/VP). The locations of these visual areas
      overlapped substantially with the PMG. In five out of six hemispheres the
      reconstructed primary visual cortex completely fell within polymicrogyric areas.
      Our results suggest that human polymicrogyric cortex is not only organized in a
      normal fashion, but is also actively involved in processing of visual information
      and contributes to normal visual perception.

PMID- 17437295
TI  - Structural brain magnetic resonance imaging of pediatric twins.
AB  - To explore the relative impact of genetic and nongenetics factors on human brain
      anatomy during childhood and adolescence development, a collaborative team from
      the Child Psychiatry Branch of the National Institute of Mental Health and
      Virginia Commonwealth University is applying structural equation modeling to
      brain morphometric data acquired via magnetic resonance imaging from a large
      sample of monozygotic and dizygotic pediatric subjects. In this report, we
      discuss methodologic issues related to pediatric neuroimaging twin studies and
      synthesize results to date from the project. Current sample size from the ongoing
      longitudinal study is approximately 150 twin pairs. Consistent themes are: (1)
      heritability is high and shared environmental effects low for most brain
      morphometric measures; (2) the cerebellum has a distinct heritability profile;
      (3) genetic and environmental factors contribute to the development of the cortex
      in a regional and age specific manner; and (4) shared genetic effects account for
      more of the variance than structure specific effects. Understanding of influences
      on trajectories of brain development may shed light on the emergence of
      psychopathology during childhood and adolescence and ultimately may guide
      therapeutic interventions.

PMID- 17437296
TI  - Pattern of body-wall muscle differentiation during embryonic development of
      Enchytraeus coronatus (Annelida: Oligochaeta; Enchytraeidae).
AB  - The plesiomorphic arrangement of body-wall musculature within the annelids is
      still under discussion. While polychaete groups show a great variety of patterns
      in their somatic muscles, the musculature of soil-living oligochaetes was thought
      to represent the characteristic pattern in annelids. Oligochaete body-wall
      muscles consist of an outer continuous layer of circular and an inner continuous
      layer of longitudinal muscles, forming a closed tube. Since designs of adult body
      musculature are influenced by evolutionary changes, additional patterns found
      during embryogenesis can give further information about possible plesiomorphic
      features. In oligochaetes, detailed cell-lineage analyses document the origin of
      the mesoderm and consequently the muscles, but later processes of muscle
      formation remain unclear. In the present work, body-wall muscle differentiation
      was monitored during embryogenesis of thesoil-living oligochaete Enchytraeus
      coronatus (Annelida) by phalloidin staining. Primary circular muscles form in a
      discrete anterior-to-posterior segmental pattern, whereas emerging longitudinal
      muscles are restricted to one ventral and one dorsal pair of primary strands,
      which continuously elongate towards posterior. These primary muscles establish an
      initial muscle-template. Secondary circular and longitudinal muscles subsequently
      differentiate in the previous spaces later in development. The prominent ventral
      primary longitudinal muscle strands on both sides eventually meet at the ventral
      midline due to neurulation, which moves the ventral nerve cord into a coelomic
      position, closing the muscle layers into a complete tube. This early embryonic
      pattern in E. coronatus resembles the adult body-wall muscle arrangements in
      several polychaete groups as well as muscle differentiation during embryonic
      development of the polychaete Capitella sp. I.

PMID- 17437297
TI  - Reappraisal of patterns of nonmarine cryptodiran turtle carotid circulation:
      evidence from osteological correlates and soft tissues.
AB  - The turtle cranial circulation has been employed as an important source of
      phylogenetic information, but recent conflicting hypotheses of relationship
      within Testudinata suggest reevaluation of the utility of characters drawn from
      this complex. As a component of a comprehensive character analysis, the
      osteological correlates of the nonmarine cryptodiran turtle carotid circulation
      are herein subjected to high-resolution X-ray computed tomography, reassessed,
      and statistically investigated. Three different patterns of osteological
      correlates, indicating three disparate cranial circulatory patterns, are
      described, and this finding is corroborated by evidence from circulatory soft
      tissues. Members of the Trionychia and Kinosternoidea exhibit patterns that
      differ from the more widespread condition found in testudinoid taxa. This result
      differs from previous work, which has indicated the presence of only two major
      cranial circulatory patterns, and suggests that while cranial circulatory
      features may be phylogenetically informative, the information contained within
      them indicates patterns of relationship different from those previously
      hypothesized.

PMID- 17437298
TI  - Assessment of non-response bias in a survey of residential magnetic field
      exposure in Taiwan.
AB  - We assessed potential non-response bias in obtaining information on residential
      extremely low-frequency power frequency magnetic field (MF) in Taiwan. All
      households occupied by children aged less than 7 years in two study districts,
      one in an urban town and the other in a rural town, were visited and solicited
      for on-site measurements in late 2003. The initial response rate was only 32%
      (33/104, urban) and 60% (61/101, rural). In the same season 1 year later, we
      performed a second survey of those who declined to be measured at the initial
      survey and successfully measured another 77 residences (50 and 27 for urban and
      rural districts, respectively). The two districts were selected mainly because
      the local public health officers were quite willing to assist the initial survey
      and to inform residents of the second survey. Except for meteorological
      conditions, the two surveys came up with very similar findings regarding
      residential characteristics and power facilities surrounding the houses. The mean
      residential MF for the urban residences was .121 and .140 micro-Tesla (microT) (P
      = .620) for the two surveys. The corresponding figures for the rural residences
      were .119 and .115 microT (P = .802). Although limited in its scope, this study
      tends to indicate that measurement studies of residential MF are less likely to
      suffer from serious selection bias if sampling is confined within a small
      district where people have similar socioeconomic characteristics.

PMID- 17437299
TI  - Developmental strategy of the endoparasite Xenos vesparum (strepsiptera,
      Insecta): host invasion and elusion of its defense reactions.
AB  - To successfully complete its endoparasitic development, the strepsipteran Xenos
      vesparum needs to elude the defense mechanisms of its host, the wasp Polistes
      dominulus. SEM and TEM observations after artificial infections allow us to
      outline the steps of this intimate host-parasite association. Triungulins, the
      mobile 1st instar larvae of this parasite, are able to "softly" overcome
      structural barriers of the larval wasp (cuticle and epidermis) without any
      traumatic reaction at the entry site, to reach the hemocoel where they settle.
      The parasite molts 48 h later to a 2nd instar larva, which moves away from the
      1st instar exuvium, molts twice more without ecdysis (a feature unique to
      Strepsiptera) and pupates, if male, or develops into a neotenic female. Host
      encapsulation involves the abandoned 1st larval exuvium, but not the living
      parasite. In contrast to the usual process of encapsulation, it occurs only 48 h
      after host invasion or later, and without any melanization. In further
      experiments, first, we verified Xenos vesparum's ability to reinfect an already
      parasitized wasp larva. Second, 2nd instar larvae implanted in a new host did not
      evoke any response by hemocytes. Third, we tested the efficiency of host defense
      mechanisms by implanting nylon filaments in control larval wasps, excluding any
      effect due the dynamic behavior of a living parasite; within a few minutes, we
      observed the beginning of a typical melanotic encapsulation plus an initial
      melanization in the wound site. We conclude that the immune response of the wasp
      is manipulated by the parasite, which is able to delay and redirect encapsulation
      towards a pseudo-target, the exuvia of triungulins, and to elude hemocyte attack
      through an active suppression of the immune defense and/or a passive avoidance of
      encapsulation by peculiar surface chemical properties.

PMID- 17437300
TI  - Chemical synthesis and in vitro biocompatibility tests of poly (L-lactic acid).
AB  - Polylactic acid 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. This article discusses the synthesis
      and characterization of poly-L-lactic acid, obtained through two synthetic
      routes: direct polycondensation reactions without organic solvents, and in a
      supercritical medium. Tin complexes were used as catalysts in both polymerization
      reactions. The polymers were characterized by (1)HNMR, IR, GPC, DSC, and TGA
      techniques. In vitro biocompatibility tests were performed with human alveolar
      bone osteoblasts and there were assessed cell adhesion, proliferation and
      viability. The poly condensation reaction proved to be an excellent synthetic
      route to produce PLA polymers with different molar mass. The formation of
      polymers from lactic acid monomer was confirmed through techniques utilized. It
      was observed that cell adhesion and viability was not disturbed by the presence
      of the polymer, although the proliferation rate was decreased when compared to
      control.

PMID- 17437301
TI  - The roles of aquaporin-4 in brain edema following neonatal hypoxia ischemia and
      reoxygenation in a cultured rat astrocyte model.
AB  - Aquaporin-4 (AQP4), a water channel protein, is abundantly expressed in
      astrocytes and plays a key role in the development of brain edema. However, it is
      not clear whether AQP4 contributes to astrocytic swelling in hypoxia-ischemia
      (HI). To investigate the roles of AQP4 in astrocytic swelling during HI and
      reoxygenation, we measured AQP4 expression and astrocytic cellular volume in
      cultured rat astrocytes following HI and reoxygenation. RNA interference was used
      to knockdown AQP4 expression (AQP4(-/-)). Real-time polymerase chain reaction and
      Western blot analysis were used to detect the inhibitory efficiency of AQP4. We
      found that the maximal inhibition of AQP4 mRNA and protein in astrocytes after
      AQP4 siRNA transfection (AQP4(-/-)) was approximately 77 and 85%, respectively,
      compared to wild-type AQP4 (AQP4(+/+)) expression. Cellular volume in both AQP4(
      /-) and AQP4(+/+) astrocytes was significantly increased during HI compared to
      cells cultured in normoxia (P<0.05). However, cellular volume during HI in AQP4(
      /-) astrocytes was significantly less than that in AQP4(+/+) astrocytes (P<0.05).
      After reoxygenation, the cellular volume gradually decreased to control levels at
      7 days in AQP4(-/-) but at 5 days in AQP4(+/+) astrocytes. The different roles of
      AQP4 during HI and reoxygenation suggest that AQP4 knockdown may protect against
      water influx in the formation of astrocyte swelling during HI, and may also delay
      water clearance in the resolution of astrocyte swelling during reoxygenation. In
      conclusion, AQP4 mediates bidirectional transport of water across astrocytes
      during HI and reoxygenation. AQP4 manipulation may serve as a novel therapeutic
      strategy during different periods of hypoxic-ischemic brain edema in neonates.

PMID- 17437302
TI  - Immunohistochemical in situ characterization of orthopedic implants on polymethyl
      metacrylate embedded cutting and grinding sections.
AB  - When investigating the tissue reaction on orthopedic implants, the cellular
      activity at the bone-implant interface is of special interest. Preparation of
      undecalcified bone sections with methylmetacrylate (MMA)-based resins allows
      evaluation of the host tissue reactions with the implant in situ. However, the
      technical workup is demanding and few reports exist on the immunohistochemical
      characterization of these sections. Rat (R), sheep (S), and human (H) samples
      were investigated. R specimens contained intramedullary rods in the rat tibia. S
      specimens were sheep tibiae with an external fixator. H specimens were obtained
      from deceased patients. Specimens were embedded in MMA-based Technovit 9100N
      using cold polymerization. Sections of 10-15 microm thickness were obtained and
      prepared for immunohistochemical staining. Good morphological detail was
      preserved in all specimens providing information about mineralization, recent
      bone formation, and bone-implant contact. The following antibodies could
      reproducibly be detected specifically: Osteopontin (R, S, H), Osteonectin,
      Cathepsin D (R, S), von Willebrand factor (R, H), Osteocalcin, ED 1 (R), CD 3, CD
      68, Keratin (H). Control procedures without adding primary antibodies showed no
      unspecific staining. Reliable detection of immunohistochemical markers of bone
      resorption, bone formation, inflammation, and angiogenesis at undecalcified
      sections with the implant in situ appears promising in enhancing our
      understanding of the cellular activity and cell-matrix interactions at the bone
      implant interface.

PMID- 17437303
TI  - Uptake of nickel from 316L stainless steel into contacting osteoblastic cells and
      metal ion interference with BMP-2-induced alkaline phosphatase.
AB  - Bone cells contacting nickel (Ni)-containing implant materials may be affected by
      Ni species via disturbed signaling pathways involved in bone cell development.
      Here we analyze effects of the Ni-containing steel 316L and major metal
      constituents thereof on bone morphogenetic protein-2 (BMP-2)-induced alkaline
      phosphatase (ALP) of MC3T3-E1 cells. While cells grew normally on 316L, cellular
      Ni content increased 10-fold vs. control within 4 days. With respect to the major
      components of 316L, Ni2+ (3-50 microM) was most inhibitory to BMP-2-induced ALP,
      whereas even 50 microM Fe3+, Cr3+, Mo5+, or Mn2+ had no such effect. In line with
      this, BMP-2-induced ALP was significantly reduced in cells on 316L. This effect
      was not prevented by the metal ion chelator diethylenetriaminepentaacetic acid
      (DTPA). Instead, DTPA abolished the stimulatory effect of BMP-2 on ALP, pointing
      to chelatable metal ions involved. Zn2+, as one possible candidate, antagonized
      the Ni2+ inhibition of BMP-2-induced ALP in both MC3T3-E1 and human bone marrow
      stromal cells. Results show that cells contacting 316L steel are exposed to
      increased concentrations of Ni which suffice to impair BMP-2-induced ALP
      activity. Zn2+, as a competitor of this inhibition, may help to restore normal
      osteoblastic function and bone development under these conditions.

PMID- 17437304
TI  - Mechanical stimulation of TMJ condylar chondrocytes encapsulated in PEG
      hydrogels.
AB  - Temporomandibular joint (TMJ) disorders are most commonly associated with TMJ
      disc dislocation and osteoarthritis, which can cause erosion of the articular
      cartilage on the head of the mandibular condyle. There has been little attention
      focused on treating the damaged condylar cartilage. Therefore, the overall goal
      of this research is to create a tissue engineering therapy for resurfacing the
      damaged cartilage of the condylar process with healthy living tissue. Initially,
      bovine condylar cartilage explants were studied to understand the tissue
      structure, composition, and gene expression of the native tissue. The cell
      response of isolated condylar chondrocytes encapsulated in photopolymerized
      poly(ethylene glycol) hydrogels as a tissue engineering scaffold was examined in
      the presence and absence of dynamic loading for up to three days of culture.
      Condylar chondrocyte viability was maintained within the PEG hydrogel constructs
      over the culture period and loading conditions. Cell response was examined
      through real-time RTPCR for collagen types I and II and aggrecan, nitric oxide
      production, cell proliferation, proteoglycan (PG) synthesis, and spatial
      distribution of extracellular matrix through histology. This study demonstrates
      that PEG hydrogel constructs are suitable for condylar chondrocyte encapsulation
      in the absence of loading. However, dynamic compressive strains resulted in
      inhibition of gene expression, cell proliferation, and PG synthesis.

PMID- 17437305
TI  - Contrasting potential of nitric oxide and peroxynitrite to mediate
      oligodendrocyte injury in multiple sclerosis.
AB  - Nitric oxide (NO) and peroxynitrite (ONOO(-)) are potential mediators of the
      injury and cytotoxicity occurring over time to oligodendrocytes in multiple
      sclerosis (MS) lesions. Our in vitro results indicate that human adult CNS
      derived oligodendrocytes are relatively resistant to NO-mediated damage. In
      contrast, human oligodendrocytes are highly susceptible to peroxynitrite-mediated
      injury. In situ, we found that inducible nitric oxide synthase (iNOS) was
      expressed in astrocytes and macrophages in all active demyelinating and
      remyelinating MS lesions examined, yet no correlation was found between numbers
      of glial cells expressing iNOS and the extent of oligodendrocyte cell death.
      Nitrotyrosine groups, indicative of the presence of peroxynitrite in vivo, could
      be detected on astrocytes, macrophages, and oligodendrocytes in MS lesions. High
      numbers of nitrotyrosine-positive oligodendrocytes were found in one MS case that
      featured extensive oligodendrocyte cell death. Our results indicate that NO alone
      is unlikely to induce oligodendrocyte injury, whereas its more potent byproduct
      peroxynitrite is a potential mediator of injury to oligodendrocytes in MS.

PMID- 17437306
TI  - Effects of calcium ion-implantation of titanium on bone cell function in vitro.
AB  - The modification of titanium (Ti) surfaces by ion-implantation has previously
      been reported to enhance osseointegration in vivo. However, the mechanisms
      underlying the apparently improved biocompatibility of these novel implant
      materials are unknown. The aim of this study is, therefore, to determine the
      precise effects of calcium ion-implanted Ti on the functional activity of bone
      cells in vitro. Flow cytometry (FCM) and the reverse transcriptase polymerase
      chain reaction (RT-PCR) were used to measure the response of bone-derived cells
      to key bone-associated components, including alkaline phosphatase (ALP), bone
      morphogenetic protein receptor-1B (BMPR-1B), bone sialoprotein (BSP), osteonectin
      (ON), and osteopontin (OPN). FCM analysis showed that BMPR-1B, BSP and
      particularly OPN were significantly up-regulated in MG-63 cells cultured on Ca
      implanted Ti compared with control nonimplanted Ti. Moreover, the effects of this
      novel Ca-Ti surface were found to be mediated, at least partly, via gene
      activation, since RT-PCR demonstrated the presence of notably elevated levels of
      OPN mRNA transcripts in the MG-63 cells. These findings thus show that Ti
      surfaces implanted with Ca ions can enhance the expression of certain bone
      associated components in vitro, and suggest that this effect could be the cause
      of the potential benefit of this material on bone in vivo.

PMID- 17437307
TI  - Thrombin potently enhances swelling-sensitive glutamate efflux from cultured
      astrocytes.
AB  - High concentrations of thrombin (Thr) have been linked to neuronal damage in
      cerebral ischemia and traumatic brain injury. In the present study we found that
      Thr markedly enhanced swelling-activated efflux of (3)H-glutamate from cultured
      astrocytes exposed to hyposmotic medium. Thr (0.5-5 U/mL) elicited small (3)H
      glutamate efflux under isosmotic conditions and increased the hyposmotic
      glutamate efflux by 5- to 10-fold, the maximum effect being observed at 15%
      osmolarity reduction. These Thr effects involve its protease activity and are
      fully mimicked by SFFLRN, the synthetic peptide activating protease-activated
      receptor-1. Thr potentiation of (3)H-glutamate efflux was largely dependent on a
      Thr-elicited increases in cytosolic Ca(2+) (Ca(2+) (i)) concentration
      ([Ca(2+)](i)). Preventing Ca(2+) (i) rise by treatment with EGTA-AM or with the
      phospholipase C blocker U73122 reduced the Thr-increased glutamate efflux by 68%.
      The protein kinase C blockers Go6976 or chelerythrine reduced the Thr effect by
      19%-22%, while Ca/calmodulin blocker W7 caused a 63% inhibition. In addition to
      this Ca(2+)-sensitive pathway, Thr effect on glutamate efflux also involved
      activation of phosphoinositide-3 kinase (PI3K), since it was reduced by the PI3K
      inhibitor wortmannin (51% inhibition). Treating cells with EGTA-AM plus
      wortmannin essentially abolished Thr-dependent glutamate efflux. Thr-activated
      glutamate release was potently inhibited by the blockers of the volume-sensitive
      anion permeability pathway, NPPB (IC(50) 15.8 microM), DCPIB (IC(50) 4.2 microM),
      and tamoxifen (IC(50) 6.6 microM. These results suggest that Thr may contribute
      to the excitotoxic neuronal injury by elevating extracellular glutamate release
      from glial cells. Therefore, this work may aid in search of neuroprotective
      strategies for treating cerebral ischemia and brain trauma.

PMID- 17437308
TI  - [Al(Al3R3)2]: prototype of a metalloid Al cluster or a sandwich-stabilized Al
      atom?

PMID- 17437309
TI  - Highly enantioselective and diastereoselective cycloaddition of cyclopropanes
      with nitrones and its application in the kinetic resolution of 2-substituted
      cyclopropane-1,1-dicarboxylates.

PMID- 17437310
TI  - Metal-assisted multicomponent reactions involving carbon monoxide--towards
      heterocycle synthesis.

PMID- 17437311
TI  - Total synthesis of the potent antitumor macrolides pladienolide B and D.

PMID- 17437312
TI  - Carbonylation of methanol on metal-acid zeolites: evidence for a mechanism
      involving a multisite active center.

PMID- 17437313
TI  - Enthalpy-driven three-state switching of a superhydrophilic/superhydrophobic
      surface.

PMID- 17437314
TI  - Total synthesis of the marine natural product (-)-cribrostatin 4 (renieramycin
      H).

PMID- 17437315
TI  - The use of unsymmetrical indirect covariance NMR methods to obtain the equivalent
      of HSQC-NOESY data.
AB  - We have recently demonstrated that unsymmetrical indirect covariance NMR methods
      can be used to mathematically calculate the equivalent of low sensitivity,
      hyphenated NMR experiments by combining data from a pair of higher sensitivity
      experiments. The present report demonstrates the application of this method to
      the combination of HSQC and NOESY spectra to provide results comparable to HSQC
      NOESY data, albeit with greater sensitivity and with considerably less
      spectrometer time.

PMID- 17437316
TI  - Hormonal imprinting: phylogeny, ontogeny, diseases and possible role in present
      day human evolution.
AB  - Hormonal (chemical) imprinting which was first observed (and named) by us in the
      seventies of the last century, is a general biological phenomenon which takes
      place when the developing receptor meets its target hormone for the first time.
      Under the effect of imprinting, receptors mature and reach their maximal binding
      capacity. It also influences the cells' hormone production and different
      functions depending on receptors and hormones. Hormonal imprinting is present
      already at the unicellular level causing the development of specific receptors
      and helping the easier recognition of useful or harmful surrounding molecules.
      The phenomenon is an important factor in the survival of the species, as the
      effect of imprinting is transmitted to the progeny cell generations. At the same
      time it possibly helps the selection of molecules which are suitable for acting
      as hormones in higher ranked animals. In mammals, hormonal imprinting takes place
      perinatally and determines the function of receptor-signal-transduction systems
      as well as hormone production for life. However, there are other critical
      imprinting periods for continuously developing cells. Excess of the target
      hormones or presence of foreign molecules which are able to bind to the
      receptors, provoke faulty imprinting in the critical periods with life-long
      morphological, biochemical, functional or behavioural consequences. As many
      receptor-bound foreign molecules are used as medical treatments and many such
      molecules are present around us and inside us as environmental pollutants, they-
      causing faulty imprinting--are able to predispose the (human) organism to
      cardiovascular, endocrine, metabolic and cancerous diseases. It seems likely that
      this effect is connected with disturbance of DNA methylation process in the
      critical periods of life. There are some signs of the transgenerational effect of
      faulty imprinting and this could be manifested in the evolution of humans by an
      epigenetic route.

PMID- 17437317
TI  - Dichlorodiphenyldichloroethylene concentrations in umbilical cord of newborns and
      determinant maternal factors.
AB  - OBJECTIVE: The aim was to identify exposure levels to
      dichlorodiphenyltrichloroethane (DDT) and to assess maternal factors as
      determinants of the serum dichlorodiphenyldichloroethylene (DDE) concentration in
      umbilical cord in newborns from the Mexican Pacific coastal area of Oaxaca State.
      MATERIALS AND METHODS: A cross-sectional study was conducted of 86 paired mothers
      and newborns from the Oaxaca community of Pochutla. Blood and umbilical cord
      blood samples were collected to determine DDT and DDE by GC. Information
      concerning possible determinant factors with regard to pesticide concentration
      was obtained by means of a questionnaire. RESULTS: A positive correlation between
      maternal and umbilical cord serum DDE concentration was observed (geometric mean
      of 7.69 microg g(-1) and 7.29, respectively). Multiple analyses showed that
      significant maternal factors related to umbilical cord serum DDE concentrations
      were: always having lived in the same community; low to high socioeconomic
      strata; accumulated breast-feeding time. CONCLUSIONS: The determinant factors
      observed in this study must be considered in future studies for the
      quantification of organochlorine concentration. In addition, these factors must
      be taken into account when preventive actions to minimize in utero exposure to
      these pesticides are carried out.

PMID- 17437318
TI  - PKD1 inhibits cancer cells migration and invasion via Wnt signaling pathway in
      vitro.
AB  - The approximately 14 kb mRNA of the polycystic kidney disease gene PKD1 encodes a
      large ( approximately 460 kDa) protein, termed polycystin-1 (PC-1), that is
      responsible for autosomal dominant polycystic kidney disease (ADPKD). The unique
      organization of its multiple adhesive domains (16 Ig-like domains/PKD domains)
      suggests that it may play an important role in cell-cell/cell-matrix
      interactions. Here we demonstrated that PKD1 promoted cell-cell and cell-matrix
      interactions in cancer cells, indicating that PC-1 is involved in the cell
      adhesion process. Furthermore in this study, we showed that PKD1 inhibited cancer
      cells migration and invasion. And we also showed that PC-1 regulated these
      processes in a process that may be at least partially through the Wnt pathway.
      Collectively, our data suggest that PKD1 may act as a novel member of the tumor
      suppressor family of genes.

PMID- 17437319
TI  - Decreased serum dependence in the growth of NIH3T3 cells from the overexpression
      of human nuclear receptor-binding SET-domain-containing protein 1 (NSD1) or
      fission yeast su(var)3-9, enhancer-of-zeste, trithorax 2 (SET2).
AB  - Nuclear receptor-binding SET-domain-containing protein 1 (NSD1), a culprit gene
      for Sotos syndrome, contains a su(var)3-9, enhancer-of-zeste, trithorax (SET)
      domain that is responsible for histone methyltransferase activity and other
      domains such as plant homeodomain (PHD) and proline-tryptophan-tryptophan-proline
      (PWWP) involved in protein-protein interactions in the C-terminal half of NSD1.
      To elucidate the function of NSD1 on cell growth, we overexpressed NSD1 in NIH3T3
      cells. Cells overexpressing NSD1 grew in the presence of 2% serum, whereas vector
      transfected cells did not. Overexpression of the C-terminal half of NSD1 but not
      the N-terminal half of NSD1 also produced cell growth under low serum
      concentration. Furthermore, overexpression in NIH3T3 of Schizosaccharomyces pombe
      SET2 which has a SET domain but not PHD or PWWP domains conferred the reduced
      serum dependence. Thus, the SET domain of NSD1 is involved in cell growth by
      modulating serum dependence.

PMID- 17437320
TI  - The importance of hormone receptor analysis in osteosarcoma cells growth
      submitted to treatment with estrogen in association with thyroid hormone.
AB  - Bone tumor incidence in women peaks at age 50-60, coinciding with the menopause.
      That estrogen (E2) and triiodothyronine (T3) interact in bone metabolism has been
      well established. However, few data on the action of these hormones are
      available. Our purpose was to determine the role of E2 and T3 in the expression
      of bone activity markers, namely alkaline phosphatase (AP) and receptor activator
      of nuclear factor kappaB ligand (RANKL). Two osteosarcoma cell lines: MG-63
      (which has both estrogen (ER) and thyroid hormone (TR) receptors) and SaOs-29 (ER
      receptors only) were treated with infraphysiological E2 associated with T3 at
      infraphysiological, physiological, and supraphysiological concentrations. Real
      time RT-PCR was used for expression analysis. Our results show that, in MG-63
      cells, infraphysiological E2 associated with supraphysiological T3 increases AP
      expression and decreases RANKL expression, while infraphysiological E2 associated
      with either physiological or supraphysiological T3 decreases both AP and RANKL
      expression. On the other hand, in SaOs-2 cells, the same hormone combinations had
      no significant effect on the markers' expression. Thus, the analysis of hormone
      receptors was shown to be crucial for the assessment of tumor potential growth in
      the face of hormonal changes. Special care should be provided to patients with T3
      and E2 hormone receptors that may increase tumor growth.

PMID- 17437321
TI  - Biochemical effects of chlorpyrifos and deltamethrin on altered antioxidative
      defense mechanisms and lipid peroxidation in rat liver.
AB  - Pesticides such as organophosphorus and organochlorine compounds commonly used in
      agriculture for achieving better quality products are toxic substances and lead
      to generation of reactive oxygen species (ROS) which have harmful effects on
      human health. While pyrethroid pesticides are used in preference to
      organophosphates and organochlorines due to their high effectiveness, low
      toxicity to non-target organisms and easy biodegradability, they may also produce
      oxidative stress. Thus, we investigated the effects of chlorpyrifos (CP, an
      organophosphate) and deltamethrin (DM, a pyrethroid pesticide) treatments at low
      and high doses on lipid peroxidation (LPO) and antioxidant enzyme activities such
      as SOD, GSH-Px and CAT in rat liver following 16 weeks exposure. Antioxidative
      defence mechanisms and lipid peroxidation in rat liver tissues display different
      responses depending on different pesticide treatments and doses. Biochemical
      analysis showed that administrations of the chlorpyrifos and deltamethrin cause
      liver damage. In the present study, we observed that lipid peroxidation levels
      are higher at high doses than at low doses, but DM caused more pronounced
      increase than CP. Experimentally, we have also observed that oxidant-antioxidant
      balance is more affected by deltamethrin treatment than by chlorpyrifos.

PMID- 17437322
TI  - Influence of maternal systemic lupus erythematosus on first-trimester combined
      screening for chromosomal abnormalities.
AB  - OBJECTIVE: To explore the effect of maternal systemic lupus erythematosus (SLE)
      on first-trimester screening markers for Down syndrome. METHODS: A retrospective
      study was conducted on 1150 normal singleton fetuses that underwent first
      trimester combined screening for Down syndrome. Fetal delta nuchal translucency
      (NT), maternal serum PAPP-A and free beta-hCG were compared between pregnancies
      with SLE (n = 10) and without preexisting maternal disease (n = 1140). RESULTS:
      The medians +/- SD for delta NT, log(10) MoM of PAPP-A and free beta-hCG +/- SD
      in pregnancies with SLE and without maternal disease were - 0.18 +/- 0.29 versus 
      0.18 +/- 0.33, 0.005 +/- 0.32 versus 0.02 +/- 0.26, and 0.22 +/- 0.19 versus -
      0.014 +/- 0.28, with a p value of 0.7, 0.98 and 0.03, respectively. CONCLUSIONS:
      Patients with preexisting SLE have increased maternal serum-free beta-hCG levels
      in the first-trimester. But, because of the multimodal procedure of risk
      calculation there is no significant difference in the screen-positive rate after
      the combined first-trimester screening for trisomy 21.

PMID- 17437323
TI  - Four cases of fetal hypoechoic hepatomegaly associated with Trisomy 21 and
      transient abnormal myelopoiesis.
AB  - OBJECTIVE: Our objective was to determine the clinical significance of fetal
      hypoechoic hepatomegaly and serial change of liver sizes. METHODS: The liver
      sizes of four fetuses with hypoechoic hepatomegaly were serially estimated by
      liver length, as measured from the dome of the right hemidiaphragm to the tip of
      the right lobe. RESULTS: All cases were associated with trisomy 21 or transient
      abnormal myelopoiesis (TAM). Two cases were trisomy 21 with TAM, one case was a
      phenotypically normal newborn, who had developed TAM during the fetal period, and
      the last case was trisomy 21 without TAM. In the last case, it is speculated that
      TAM had developed and regressed completely before birth. Two cases, whose
      hepatomegaly had improved before birth, showed good prognosis and the other two
      cases, in whom improvement had not been observed, resulted in death after birth
      by liver failure. CONCLUSION: These experiences show that one of the differential
      diagnoses of hypoechoic hepatosplenomegaly is TAM and that the change of live
      size is a predictor of prognosis.

PMID- 17437324
TI  - Prenatal thrombosis of the inferior vena cava and the renal veins.
AB  - OBJECTIVE: This manuscript discusses the clinical presentation, diagnosis,
      pathophysiology and possible etiologies of prenatal thrombosis of the inferior
      vena cava and renal veins. METHODS: Eleven cases were identified through a
      Medline search of the English literature. These cases were reviewed, together
      with a recent case that was treated in our medical center. RESULTS: Fetal
      thrombosis in the aforementioned vessels, presented as hydrops fetalis (33%),
      acute fetal distress (42%), or as an incidental prenatal ultrasound finding
      (25%). Underlying maternal conditions were present in 58%, and included chronic
      conditions (hypertension and diabetes mellitus), acute conditions (pyelonephritis
      and preeclampsia) and thrombophilia. In 42% cases, the prenatal ultrasound scan
      revealed an enlarged and hyper-echogenic affected kidney. CONCLUSION:
      Intrauterine fetal venous thrombosis is a rare phenomenon, probably attributed to
      a multifactorial process. These factors may include inherited thrombophilia as
      well as prothrombotic clinical conditions.

PMID- 17437325
TI  - Prenatal diagnosis of complete trisomy 19q.
AB  - This communication presents the first case of complete trisomy 19q, prenatally
      detected by ultrasound investigation. Real-time high-resolution ultrasound
      examination was performed at 19 weeks of gestation. After termination of the
      pregnancy, autopsy investigation was done. GTG-banding, fluorescence in situ
      hybridization m-(FISH) analysis, and FISH analysis with a 19q subtelomeric
      specific probe were used for identification of the fetal karyotype. Sonographic
      examination revealed an enlarged cisterna magna, cerebellar hypoplasia and
      aplasia of the inferior part of the vermis, combined and bilateral kidney
      malformations, significant nuchal fold, absence of fetal nasal bones, and
      intracardial calcifications. Autopsy confirmed ultrasound findings, but also
      revealed situs viscerum inversus of the lungs. Fetal karyotype was defined as:
      46,XY,der(21)t(19;21)(q11;p13)mat. Our ultrasound and autopsy findings will
      certainly contribute to better knowledge of phenotype characterization of this
      rare chromosomal disorder.

PMID- 17437326
TI  - Use of desmopressin in elderly patients in Denmark.
AB  - PURPOSE: Against the background of the approval of the use of desmopressin in the
      treatment of nocturia in adults, the aim of the present study was to describe
      patterns of its use in elderly patients in Denmark from 2000 to 2004. METHODS:
      Data were obtained from the Danish Register of Medicinal Product Statistics on
      nationwide sales of desmopressin and two commonly used measures of drug
      utilisation: 1-year prevalence (number of patients treated at least once during 1
      year/1000 inhabitants) and therapeutic intensity (Daily Defined Doses (DDD)/1000
      inhabitants/day). RESULTS: In 2002, the 1-year prevalence rose ranging from a 5
      fold increase among men aged 60-69 years to a 14-fold increased prevalence in men
      >/=90 years. In women, relative increases of the same magnitude were noted.
      Similarly, marked increases of the therapeutic intensities were observed in both
      men and women in 2002, this was followed by steady growth in most age groups. By
      the end of the study period in 2004, the highest therapeutic intensities were
      observed in men (1.06 DDD/1000 inhabitants/day) and women (0.92 DDD/1000
      inhabitants/day) aged 80-89 years. CONCLUSION: After approval in 2002 of the use
      of desmopressin in the management of nocturia in adults, a substantial increased
      utilisation was observed in patients >/=80 years. Given the high prevalence of
      risk factors for hyponatremia in these elderly patients, the pattern of
      utilisation is noteworthy and may need to be reviewed.

PMID- 17437327
TI  - Molecular packing and symmetry of two-dimensional crystals.
AB  - Periodic arrangements on surfaces resulting from monolayer formation are critical
      in determining the electronic structure of thin films, the adhesion of surface
      coatings, the properties of lubricants, and the polymorphic form of
      heteronucleated crystals. Unlike substrate-directed chemisorption, the process of
      physisorption is highly responsive to molecular structure and stands out as a
      controllable method of creating variable surface patterns with periodicities on
      the low end of the nanoscale. Despite decades of study focused upon such ordered
      structures, the principles guiding the formation of these two-dimensional
      crystals have been obscured by the lack of a systematic and critical compilation.
      Thus, prediction of two-dimensional structure based upon the composition of the
      individual building blocks remains in its infancy. Here we demonstrate through
      the compilation and analysis of a database of two-dimensional structures that
      molecular-scale patterns are dictated by the same factors that determine bulk
      crystal structure, but these factors give rise to different preferred packing
      symmetries. In marked contrast to three-dimensional systems, achiral molecules in
      two-dimensional crystals are likely to adopt chiral structures, and racemic
      mixtures are expected to produce enantiopure domains. The determination of plane
      group frequencies allowed experimental verification of Kitaigorodskii's 50-year
      old theory of close packing as applied to two-dimensional tiling. This
      fundamental comparison between bulk crystals and physisorbed monolayers provides
      new tools and directions for future exploration in the engineering of surfaces
      with prescribed two-dimensional patterns.

PMID- 17437328
TI  - Self-excited drop oscillations in electrowetting.
AB  - We studied millimeter-sized aqueous sessile drops in an ambient oil environment
      in a classical electrowetting configuration with a wire-shaped electrode placed
      at a variable height above the substrate. Within a certain range of height and
      above a certain threshold voltage, the drop oscillates periodically between two
      morphologies where it is either attached to the wire or detached from it. We
      determine the range of control parameters, wire height, and voltage in which
      oscillations occur and explain it by a simple capillary model. Furthermore, we
      analyze the dynamics of the oscillations using high-speed video microscopy and
      numerical fluid dynamics modeling. We develop a one-dimensional harmonic
      oscillator model that describes the dependence of the drop oscillations on the
      relevant intrinsic (surface tension, viscosity, density) and extrinsic (wire
      height, voltage) parameters.

PMID- 17437330
TI  - Calculating optimal modulation periods to maximize the peak capacity in two
      dimensional HPLC.
AB  - Theoretical calculations are presented to optimize modulation period for maximum
      total peak capacity in comprehensive two-dimensional HPLC (2D-HPLC) taking into
      account the effect of modulation on the apparent peak capacity of the first
      dimension (1D) separation. Results indicate that modulation periods are most
      favorable when they are adjusted to approximately 2.2-4 times the standard
      deviation of a 1D peak in order to avoid excessively short run times at the
      second dimension (2D). Data are presented that effective peak capacities of
      several thousand in 60 min can be expected for practical 2D-HPLC conditions,
      utilizing 1D gradient elution followed by 2D isocratic elution, that remain at
      approximately 50-70% of the theoretical maximum peak capacity. This work suggests
      that lower modulation frequencies and longer 2D separation times than previously
      proposed are favorable under realistic chromatographic conditions, alleviating
      some practical problems associated with 2D-HPLC.

PMID- 17437329
TI  - Proteomic mapping of 4-hydroxynonenal protein modification sites by solid-phase
      hydrazide chemistry and mass spectrometry.
AB  - The modification of proteins by the cytotoxic, reactive aldehyde 4-hydroxynonenal
      (HNE) is known to alter protein function and impair cellular mechanisms. In order
      to identify susceptible amino acid sites of HNE modification within complex
      biological mixtures by microcapillary liquid chromatography and linear ion trap
      tandem mass spectrometry, we have developed a solid-phase capture and release
      strategy that utilizes reversible hydrazide chemistry to enrich HNE-modified
      peptides. To maximize the detection of fragment ions diagnostic of HNE
      modification, both neutral loss-dependent acquisition of MS/MS/MS spectra and the
      pulsed Q dissociation operation mode were employed. When the solid-phase
      hydrazide enrichment strategy was applied to a yeast lysate treated with HNE, 125
      distinct amino acid sites of HNE modification were mapped on 67 different
      proteins. The endogenous susceptibility of many of these proteins to HNE
      modification was demonstrated by analyzing HNE-treated yeast cell cultures with a
      complementary biotin hydrazide enrichment strategy. Further analysis revealed
      that the majority of amino acid sites susceptible to HNE modification were
      histidine residues, with most of these sites being flanked by basic amino acid
      residues, and predicted to be solvent exposed. These results demonstrate the
      effectiveness of this novel strategy as a general platform for proteome-scale
      identification of amino acid sites susceptible to HNE modification from within
      complex mixtures.

PMID- 17437331
TI  - Electrochemistry and electrocatalytic properties of hemoglobin in layer-by-layer
      films of SiO2 with vapor-surface sol-gel deposition.
AB  - In this paper, layer-by-layer {Hb/SiO2}n films assembled by alternate adsorption
      of positively charged hemoglobin (Hb) and vapor-surface sol-gel deposition of
      silica at 50 degrees C onto a glassy carbon electrode were reported. The result
      films were characterized with cyclic voltametery, electrochemical impedance
      spectroscopy, UV-vis spectroscopy, and SEM, and the direct electrochemical and
      electrocatalytic properties of Hb in these layer-by-layer films were
      investigated. A pair of well-defined quasi-reversible cyclic voltammetric peaks
      were observed, and the formal potential of the heme FeIII/FeII redox couple was
      found to be -0.330 V(vs SCE). The electron-transfer behavior of Hb in {Hb/SiO2}n
      films was dependent on the vapor temperature, the number of layers, and the pH of
      the Hb solution, based on which a set of optimized conditions for film
      fabrication was inferred. The hemoglobin in{Hb/SiO2}n films displayed good
      electrocatalytic activity to the reduction of hydrogen peroxide, and H2O2 had
      linear current response from 1.0 x 10(-6) to 2.0 x 10(-4) M with a detection
      limit of 5.0 x 10(-7) M (S/N = 3). The apparent heterogeneous electron-transfer
      rate constant (ks) was 1.02 +/- 0.03 s(-1), and the apparent Michaeli-Menten
      constant (Kmapp) was 0.155 mM, indicating a potential application in the third
      generation biosensor.

PMID- 17437332
TI  - Concentration gradient immunoassay. 1. An immunoassay based on interdiffusion and
      surface binding in a microchannel.
AB  - We describe a novel microfluidic immunoassay method based on the diffusion of a
      small-molecule analyte into a parallel-flowing stream containing a cognate
      antibody. This interdiffusion results in a steady-state gradient of antibody
      binding site occupancy transverse to convective flow. In contrast to the
      diffusion immunoassay (Hatch, A.; Kamholz, A. E.; Hawkins, K. R.; Munson, M. S.;
      Schilling, E. A.; Weigl, B. H.; Yager, P. Nat. Biotechnol. 2001, 19, 461-465.),
      this antibody occupancy gradient is interrogated by a sensor surface coated with
      a functional analogue of the analyte. Antibodies with at least one unoccupied
      binding site may specifically bind to this functionalized surface, leading to a
      quantifiable change in surface coverage by the antibody. SPR imaging is used to
      probe the spatial distribution of antibody binding to the surface and, therefore,
      the outcome of the assay. We show that the pattern of antibody binding to the SPR
      sensing surface correlates with the concentration of a model analyte (phenytoin)
      in the sample stream. Using an inexpensive disposable microfluidic device, we
      demonstrate assays for phenytoin ranging in concentration from 75 to 1000 nM in
      phosphate buffer. At a total volumetric flow rate of 90 nL/s, the assays are
      complete within 10 min. Inclusion of an additional flow stream on the side of the
      antibody stream opposite to that of the sample enables simultaneous calibration
      of the assay. This assay method is suitable for rapid quantitative detection of
      low molecular weight analytes for point-of-care diagnostic instrumentation.

PMID- 17437333
TI  - Concentration gradient immunoassay. 2. Computational modeling for analysis and
      optimization.
AB  - A novel microfluidic surface-based competition immunoassay, termed the
      concentration gradient immunoassay (described in detail in a companion paper
      (Nelson, K.; Foley, J.; Yager, P. Anal. Chem. 2007, 79, 3542-3548.) uses surface
      plasmon resonance (SPR) imaging to rapidly measure the concentration of small
      molecules. To conduct this assay, antibody and analyte are introduced into the
      two inlets of a T-sensor (Weigl, B. H.; Yager, P. Science 1999, 283, 346-347.
      Kamholz, A. E.; Weigl, B. H.; Finlayson, B. A.; Yager, P. Anal. Chem. 1999, 71,
      5340-5347). Several millimeters downstream, antibody molecules with open binding
      sites can bind to a surface functionalized with immobilized antigen. This space-
      and time-dependent binding can be sensitively observed using SPR imaging. In this
      paper, we describe a complex three-dimensional finite element model developed to
      better understand the dynamic processes occurring with this assay. The model
      shows strong qualitative agreement with experimental results for small-molecule
      detection. The model confirms the experimental finding that the position within
      the microchannel at which the antibody binds to the immobilized analyte may be
      used to quantify the concentration of analyte in the sample. In addition, the
      model was used to explore the sensitivity of assay performance to parameters such
      as antibody and analyte concentrations, thereby giving insight into ways to
      optimize analysis speed and accuracy. Given the experimental verification of the
      computational results, this model serves as an efficient method to explore the
      influence of the flow rate, microchannel dimensions, and antibody concentration
      on the sensitivity of the assay.

PMID- 17437334
TI  - Ultraperformance liquid chromatography-tandem mass spectrometry analysis of
      stimulatory drugs of abuse in wastewater and surface waters.
AB  - Ultraperformance liquid chromatography coupled to electrospray tandem mass
      spectrometry was used for the rapid and simultaneous analysis of 15 stimulatory
      drugs in water. Cocaine, amphetamine-related compounds, LSD, ketamine, PCP,
      fentanyl, and metabolites, among the controlled drugs, and nicotine, caffeine,
      and their metabolites, among the noncontrolled drugs, were studied.
      Chromatographic separation was achieved in less than 4.5 min, with improved peak
      resolution and sensitivity. Identification and quantification of the compounds of
      interest was performed by selected reaction monitoring, using an electrospray
      ionization source. Isotope dilution (except for paraxanthine) was used for
      quantitation. Quality parameters of the method were established, and limits of
      quantification were obtained for controlled drugs in surface waters from 0.1 to
      3.1 ng/L and in wastewaters from 0.2 to 4.0 ng/L. Run-to-run and day-to-day
      precisions were evaluated in different water matrixes (Milli-Q water, surface
      water, wastewater). To assess the presence of these drugs in real water samples,
      the optimized method was applied to the analysis of wastewater and surface river
      water. The analysis of several samples from wastewater treatment plants in
      northeast Spain revealed the presence of drugs such as cocaine and amphetamine
      related compounds, in both influent and effluent samples. Cocaine metabolite and
      MDMA (ecstasy) were also found in surface waters while nicotine and caffeine were
      detected in all the analyzed samples. The results obtained demonstrate that the
      presence of these drugs in the aquatic media must be considered a matter of
      environmental concern.

PMID- 17437335
TI  - Online preconcentration by transient isotachophoresis in linear polymer on a
      poly(methyl methacrylate) microchip for separation of human serum albumin
      immunoassay mixtures.
AB  - Online preconcentration of human serum albumin (HSA) and its immunocomplex with a
      monoclonal antibody by on-chip transient isotachophoresis is reported. An 800
      fold signal enhancement was achieved following the preconcentration on standard
      cross-channel microchips made of poly (methyl methacrylate). Sample injection,
      preconcentration, and separation were done continuously and controlled solely by
      a sequential voltage switching program. The preconcentration was followed by on
      chip nondenaturing gel electrophoresis in methylcellulose solution. The method
      was applied to microchip electrophoresis immunoassay of HSA. Baseline separation
      of HSA and its immunocomplex was achieved in 25 s in the first 1 cm of the
      microchannel. In a direct immunoassay, the minimum detectable concentration of
      fluorescent labeled HSA by laser-induced fluorescence detection was 7.5 pM.

PMID- 17437336
TI  - Determination of (Oxy)thioarsenates in sulfidic waters.
AB  - Although it has long been known that soluble arsenic-sulfur (As-S) compounds
      exist in sulfidic waters and may play significant roles in several important
      processes in the biogeochemical arsenic cycle, no suitable analytical methods
      exist for their determination. We provide evidence that the four homologue
      (oxy)thioarsenates, mono-, di-, tri-, and tetrathioarsenate (AsO3S3-, AsO2S23-,
      AsOS33- and AsS43-), can be formed in geochemical model reactions between
      arsenite and sulfide under anoxic conditions (through currently unknown reaction
      mechanisms) and that these compounds appear to be major As species in natural
      sulfidic waters. These As-S species are quantified by anion-exchange
      chromatography-inductively coupled plasma mass spectrometry (AEC-ICPMS) with
      instrumental detection limits of approximately 0.1 nmol of As L(-1) in undiluted
      samples; arsenite, arsenate, and monomethylarsenate are quantified as well, but
      dimethylarsenate cannot be analyzed by this technique. Sulfur in the eluting
      peaks can be measured as SO+ with detection limits of approximately 0.1 micromol
      of S L(-1). The (oxy)thioarsenates were synthesized in solution and characterized
      by electrospray-tandem mass spectrometry (ES-MS-MS). In geochemical model
      solutions, we confirmed that both the AEC-ICPMS retention times and the ES-MS-MS
      spectra of the reaction products of sulfide and arsenite matched the synthesized
      (oxy)thioarsenate standards; for natural waters, the mass spectrometric
      confirmation was unsuccessful, due to matrix interferences.

PMID- 17437337
TI  - Multicolor quantum dot encoding for polymeric particle-based optical ion sensors.
AB  - Multicolor quantum dot-encoded polymeric microspheres are prepared with
      controllable and uniform doping levels that function as chemical sensors on the
      basis of bulk optode theory. TOP/TOPO-capped CdSe quantum dots and CdTe quantum
      dots capped with CdS (lambdaem = 610 and 700 nm, lambdaex = 510 nm) are blended
      with a THF solution of poly(methyl methacrylate-co-decyl methacrylate), poly(n
      butylacrylate), or poly(vinyl chloride) plasticized with bis(2-ethylhexyl)
      sebacate without a need for ligand exchange. Polymeric microspheres are generated
      under mild, nonreactive conditions with a particle caster that breaks down a
      polymer stream containing the quantum dots into fine droplets by the vibration of
      a piezocrystal. The resulting microspheres exhibit uniform size and fluorescence
      emission intensities. Fluorescent bar codes are obtained by subsequent doping of
      two quantum dots with different colors and mass ratios into the microspheres. A
      linear relationship is found between the readout fluorescence ratio of the two
      types of nanocrystals and the mixing ratio. Quantum dot-encoded ion sensing
      optode microspheres are prepared by simultaneous doping of sodium ionophore X,
      chromoionophore II, a lipophilic tetraphenylborate cation exchanger, and TOPO
      capped CdSe/CdS quantum dot as the fluorescent label. A net positive charge of
      the quantum dots is found to induce an anion-exchange effect on the sensor
      function, and therefore, an increased concentration of the lipophilic cation
      exchanger is required to achieve proper ion sensing properties. The modified
      quantum dot-labeled sodium sensing microspheres show satisfactory sodium response
      between 10(-4) and 0.1 M at pH 4.8, with excellent selectivity toward common
      interferences. The amount of the carried positive charges of the CdSe quantum
      dots is estimated as 2.8 mumol/g of quantum dots used in this study.

PMID- 17437338
TI  - NMR studies of interactions between C-terminal tail of Kir2.1 channel and PDZ1,2
      domains of PSD95.
AB  - Control of surface expression of inwardly rectifying potassium (Kir) channels is
      important for regulating membrane excitability. Kir2 channels have been shown to
      interact directly with PDZ-containing proteins in the postsynaptic density (PSD).
      These scaffold proteins, such as PSD95, bind to Kir2.1 channels via a PDZ-binding
      motif (T/S-x-Phi) in the C-terminal tail (SEI428). By utilizing a
      multidimensional solution NMR approach, we show that the previously unresolved
      structure of Kir2.1 tail (residues 372-428) is highly flexible. Using in vitro
      binding assays, we determined that shortening the flexible tail of Kir2.1
      preceding the C-terminal region (residues 414-428) does not significantly disrupt
      PDZ binding. We also investigated which amino acids in the Kir2.1 tail associated
      with PSD95 PDZ1,2 by NMR spectroscopy, revealing that a stretch of 12 C-terminal
      amino acids is involved in interaction with both PDZ domains (residues 417-428).
      Deletion of the 11 amino acids preceding the C-terminal tail, Delta414-424,
      completely disrupts binding to PSD95 PDZ1,2. Therefore, the molecular interfaces
      formed between PDZ domains and Kir2.1 tail involve regions outside the previously
      identified binding motif (SEI428) and may be important for additional channel
      specific interactions with associating PDZ-containing proteins.

PMID- 17437339
TI  - Prenylation of Ras facilitates hSOS1-promoted nucleotide exchange, upon Ras
      binding to the regulatory site.
AB  - The oncoprotein Ras is anchored in lipid membranes due to its C-terminal lipid
      modification. The ubiquitously expressed Ras nucleotide exchange-factor hSOS1
      promotes nucleotide exchange and thus Ras activation. This reaction is enhanced
      by a positive feedback loop whereby activated Ras binds to an allosteric site of
      SOS to enhance GEF activity. Here we present biochemical data showing that
      prenylation of both active site bound and allosterically bound N-Ras is required
      for efficient hSOS1-promoted nucleotide exchange. Our results indicate that
      prenyl sensitivity of the allosteric feedback-activation is mediated by the PH
      domain of hSOS1. Farnesylation of Ras thereby allows hSOS1 to bind even GDP
      loaded allosteric regulator to maintain basal hSOS1-activity.

PMID- 17437340
TI  - Expression of atrial natriuretic peptide, progesterone, apoptosis-related
      proteins and caspase-3 in in vitro luteinized and leptin-treated porcine
      granulosa cells.
AB  - OBJECTIVE: Our aim was to examine the expression patterns of ANP, the rate of
      apoptosis bcl-2 and p53 expression and caspase-3 activity and progesterone (P)
      production in porcine granulosa cells (pGCs) stimulated in vitro for
      luteinization and after treatment with leptin. METHODS: Freshly isolated
      prepubertal pGCs were cultured as monolayers for 24 h, subsequently FSH was
      supplemented for 24 h, and finally LH was added to a part of the cells for 24 h
      to induce luteinization. The effect of leptin on in vitro luteinized pGCs was
      tested by the addition of 10 ng/ml human recombinant leptin (hrL) 24 h after LH
      administration. Indirect immunofluorescence for ANP, bcl-2 and p53 expression was
      used, P production was assayed by direct enzyme immunoassay (EIA) and
      colorimetric AcDEVD-Pna assay for caspase-3 activity was applied. RESULTS:
      Stimulation of prepubertal pGCs with FSH resulted in a moderate expression of ANP
      and elevation in P production. When FSH treatment was followed by LH, the
      pronounced expression of ANP was observed in all cells. Suppressive effect of FSH
      and LH on p53 expression and caspase-3 activity with parallel increase in bcl-2
      expression and increased P production was observed. The treatment of in vitro
      luteinized (FSH/LH-stimulated) pGCs with leptin did not influence the expression
      of ANP. However, in FSH/LH plus leptin treated cells the concomitant increase in
      bcl-2 expression and parallel inhibitory effect on p53 expression and caspase-3
      activity was noted, compared to control cells without any significant increase in
      P production. CONCLUSION: The present data demonstrated the positive relationship
      between ANP expression and P production in pGCs stimulated for luteinization in
      vitro by FSH and LH, as well as their antiapoptotic role mediated presumably by
      cGMP accumulation in the luteinized pGCs. A direct anti-apoptotic effect of
      leptin on in vitro luteinized pGCs, without any significant modulation of P
      production, was documented.

PMID- 17437341
TI  - Vitamin D and its metabolites--supply of patients with various endocrine
      disorders and comparison of analytical methods.
AB  - OBJECTIVE: Vitamin D is important not only for its effect on the homeostasis of
      calcium, but also for its anti-proliferative, pro-differentiation, pro-apoptotic
      and immuno-modulating effects in the tissues of living organisms. This work
      describes the results of serum 25(OH)D (n=2175) and 1alpha,25(OH)2D (n=2271)
      radioimmunoassays (RIA) conducted at the Institute of Endocrinology in Prague
      (Czech Republic) during the period of 2004-2006. METHODS: Serum concentrations of
      vitamin D metabolites were determined by RIA kits from IDS Ltd., Boldon, UK. In a
      group of 20 healthy volunteers, results obtained using the RIA kit were compared
      with those obtained after serum extraction with acetonitrile, subsequent
      chromatographic (RP HPLC) separation of 25(OH)D and its detection in collected
      fractions using the same RIA kit from IDS. RESULTS: The mean concentrations +/-
      S.D. in the samples studied were 76.4 +/- 45.6 nmol/l for 25(OH)D and 88.9 +/-
      45.1 pmol/l for 1alpha,25(OH)2D. The mean concentrations of both metabolites were
      higher in women than in men, but only the difference for 1alpha,25(OH)2D) was
      statistically significant (p=0.0000). The lowest concentrations of 25(OH)D or
      1alpha,25(OH)2D were found in patients with hyperparathyroidism, the highest
      concentrations those treated with cholecalciferol for osteoporosis and vitamin D
      deficiency. The relationship between 25(OH)D and 1alpha,25(OH)2D was expressed by
      the equation 1alpha,25(OH)2D = 71.0845 + 0.1890 * 25(OH)D (n=1065, p=0.0000,
      R2=0.0343). Based on the RIA results, only 4 % of individuals were inadequately
      supplied with 25(OH)D, 79 % were supplied adequately and almost 17 % were
      supplied more than adequately. Similarly, 1alpha,25(OH)2D shows inadequate
      concentration in 15 % of the individuals tested, 59 % of these individuals were
      within the reference range and 26 % had values exceeding the upper limit of the
      reference range. The mean concentrations of 25(OH)D obtained by HPLC separation
      were in average by 8 % higher than those obtained using only the RIA kit.
      CONCLUSION: Interpretation of studies dealing with vitamin D stores must be based
      on precise and correct analytical procedures. However, only a few information
      exists about the influence of other vitamin D metabolites and conjugates on the
      concentration of immunoanalytically measured serum 25(OH)D or 1alpha,25(OH)2D.

PMID- 17437342
TI  - Intraoperative parathyroid hormone measurement in thyroidectomized patients:
      preliminary report.
AB  - BACKGROUND: Hypocalcemia is the most frequent complication after thyroid surgery.
      Intraoperative measurement of parathormone levels (ioPTH) in patients undergoing
      thyroid surgery has been recently described as an accurate method of predicting
      postoperative parathyroid dysfunction. The aim of the study was to evaluate
      utility of ioPTH and parathormone level measured 24 hours after surgery (24PTH)
      as prognostic factors of hypoparathyroidism and consequent hypocalcemia. SUBJECTS
      AND METHODS: Fifty-four patients (50 females and 4 males) underwent 55
      operations: subtotal thyroidectomy (44), total thyroidectomy (8), completion
      thyroidectomy due to goiter reoccurrence and cancer (2 and 1 patients,
      respectively). PTH and serum calcium levels were assessed one day prior to
      surgery, intraoperatively during wound closure, on the first postoperative day
      and 2 months after surgery. Hypoparathyroidism was defined as parathormone level
      less than 15 pg/ml. RESULTS: Seventeen patients presented ioPTH levels below 15
      pg/ml. Twelve of them had low 24PTH levels. Only one patient with ioPTH (but not
      24PTH) below 15 pg/ml developed persistent hypoparathyroidism, resulting in low
      parathormone level 2 months after surgery. Three investigated subjects with ioPTH
      greater than 15 pg/ml had low 24PTH levels but none of them developed persistent
      hypoparathyroidism. One patient with ioPTH and 24PTH within reference range
      presented hypoparathyroidism at the 2-month follow-up, presumably due to
      postoperative iodotherapy. CONCLUSIONS: This study suggests that ioPTH and 24PTH
      levels are not useful prognostic factors of persistent hypoparathyroidism but may
      indicate transient parathyroid gland dysfunction.

PMID- 17437343
TI  - Potential benefit of oral calcium/vitamin D administration for prevention of
      symptomatic hypocalcemia after total thyroidectomy.
AB  - OBJECTIVE: To evaluate routine oral calcium and vitamin D administration for
      preventing symptoms of hypocalcemia after total thyroidectomy. SUBJECTS AND
      METHODS: A total of 487 consecutive patients were prospectively randomized into
      two groups in terms of routine oral calcium and vitamin D supplementation: In the
      control group (244 patients) the treatment was not routinely started after
      surgery, whereas the treated group (243 patients) received routine
      supplementation that started on postoperative day 1. RESULTS: Patients of treated
      group had only minor hypocalcemia symptoms, whereas 7 patients of control group
      experienced carpopedal spasm as a major symptom (p<0.001). None of the patients
      in the treated group required intravenous calcium administration. Average
      hospital stay of the treated group patients was significantly shorter than that
      of control group (p<0.001). CONCLUSIONS: Routine postoperative calcium and
      vitamin D supplementation therapy may be useful for the prevention of symptomatic
      hypocalcemia after total thyroidectomy and may allow for a safe and early
      discharge from the hospital.

PMID- 17437344
TI  - Anaplastic thyroid carcinoma with long term survival after combined treatment:
      case report.
AB  - Anaplastic thyroid carcinoma (ATC) is associated with an almost uniformly rapid
      and lethal clinical course. ATC grows rapidly and invades surrounding tissues at
      an early stage. Despite surgery, chemotherapy and radiotherapy, few patients with
      ATC live more than 1 year follow-up diagnosis. The mean survival is reported to
      be only 7.2 months. Treatment of ATC is still controversial because of its rarity
      and advanced stage at the time of diagnosis. We report herein an unusual case of
      ATC, 35 year old woman. She is alive without evidence of recurrence more than 36
      months after combined therapy.

PMID- 17437345
TI  - Prostate tumours--histological classification and molecular aspects of prostate
      tumorigenesis.

PMID- 17437346
TI  - Improvement in the evaluation of Fos-neuropeptide colocalization by employing
      free-floating cryosections of delicate thickness: double and triple colored
      immunohistochemistry.
AB  - OBJECTIVE: The present study was aimed to select a methodical approach to
      optimize the thickness of cryo-processed free-floating sections for precise
      recognition between a single Fos signal and Fos/neuropeptide colocalizations in
      sequential double or triple colored immunohistochemical stainings. For this
      purpose brain sections of variable (5-20 microm) thickness were tested utilizing
      enzyme-substrate detection system employing oxytocin (OXY) and vasopressin (AVP)
      antisera. METHODS: The animals were perfused by fixative 90 min after i.p.
      administration of 5 ml of hypertonic saline (1.5 M NaCl) which was used to
      stimulate the hypothalamic osmosensitive neurons. The brains were removed, soaked
      with 30% sucrose in 0.1 M PBS, cryo-sectioned throughout the hypothalamus into 5,
      10, 15, and 20 microm thick coronal sections, collected and washed in 0.2 M
      glycine buffer for 10-15 min, and finely stored in 0.1 M PBS. Single Fos and
      Fos/OXY and Fos/ OXY/AVP colocalizations were processed employing avidin-biotin
      peroxidase (ABC) complex and diaminobenzidine chromogen with or without adding
      Nickel chloride salt as a black and blue color inducer. Evaluation of the Fos
      neuropeptide co-labeled perikarya manifestation was performed on a computerized
      Leica light microscopy. RESULTS: The present data demonstrate that cryoprocessing
      enables generate free- floating sections of 5, 10, 15, and 20 microm thickness.
      Except the 5 microm thickness, all the other sections sizes tested exhibited well
      preserved tissue stability and excellent immunohistochemical properties either
      for single Fos reaction or double Fos/OXY and triple Fos/OXY/AVP costainings.
      CONCLUSIONS: We adapted and optimized Fos immunohistochemistry for use of fixed
      and cryocut processed free-floating brain sections. The present data indicate
      that except 5 mum thickness all the other sorts of cryosections tested were
      sufficiently resilient for performing a sequential double or triple colored
      immunohistochemical stainings. However, 10 mum thickness reached the borderline
      of the handling safety, therefore, 15 mum section thickness will be the thickness
      of the choice recommended, which gave relevant immunoreaction, retained good
      tissue preservation, and ensured an appropriate clarity for accurate recognition
      between a single and colocalized Fos signals.

PMID- 17437348
TI  - Community engagement: leadership tool for catastrophic health events.
AB  - Disasters and epidemics are immense and shocking disturbances that require the
      judgments and efforts of large numbers of people, not simply those who serve in
      an official capacity. This article reviews the Working Group on Community
      Engagement in Health Emergency Planning's recommendations to government decision
      makers on why and how to catalyze the civic infrastructure for an extreme health
      event. Community engagement--defined here as structured dialogue, joint problem
      solving, and collaborative action among formal authorities, citizens at-large,
      and local opinion leaders around a pressing public matter--can augment officials'
      abilities to govern in a crisis, improve application of communally held resources
      in a disaster or epidemic, and mitigate community wide losses. The case of
      limited medical options in an influenza pandemic serves to demonstrate the civic
      infrastructure's preparedness, response, and recovery capabilities and to
      illustrate how community engagement can improve pandemic contingency planning.

PMID- 17437349
TI  - Public health response to an anthrax attack: an evaluation of vaccination policy
      options.
AB  - A discrete-time, deterministic, compartmental model was developed and analyzed to
      provide insight into how the use of anthrax vaccine before or after a large-scale
      attack can reduce casualties. The model accounts for important response and
      protection factors such as antibiotic and vaccine efficacy, the protective
      effects of buildings, the timing of emergency response, and antibiotic adherence
      and vaccine coverage in the population prior to the attack. The relative benefit
      of pre- versus post-exposure vaccination is influenced by the timing of the post
      exposure antibiotic distribution campaign as well as assumptions of antibiotic
      adherence. The results indicate that, regardless of which vaccination policy is
      adopted, a rapid and effective post-attack medical response has a large impact on
      the number of lives that can be saved by a post-exposure prophylaxis (PEP)
      campaign. A sensitivity analysis of the model indicates that uncertainty in
      medical efficacy and the time to initiate a PEP campaign are the model parameters
      that have the greatest impact on the number of predicted deaths. It is shown that
      for each day that a mass prophylaxis campaign is delayed, more casualties and
      deaths result than for each day that the completion of the campaign is delayed.

PMID- 17437350
TI  - Bioterrorism-related inhalational anthrax: can extrapolated adult guidelines be
      applied to a pediatric population?
AB  - OBJECTIVE: Since the 2001 anthrax attacks, an extensive body of literature has
      evolved, but there has been a limited focus on the management of pediatric
      specific issues. We looked at the symptom complexes of all pediatric patients
      presenting to the emergency department of our hospital during this period and
      examined whether their presentations would likely allow current guidelines to be
      used as potential screening criteria to identify children infected with anthrax.
      METHODS: We retrospectively reviewed emergency department records of all adult
      and pediatric patients (up to the age of 21 years) at Inova Fairfax Hospital
      during this time, when a large, and at the time ill-defined, group in the
      Washington, DC, metropolitan area was at risk for pulmonary anthrax. Two cases of
      anthrax infection were identified at this hospital in exposed adult postal
      workers. Screening algorithms (described by Mayer et al. and Hupert et al.) were
      applied to adult and pediatric patients with the presence of fever (38 degrees
      C), tachycardia, or other symptoms compatible with pulmonary anthrax.
      Specifically, the usefulness of these guidelines as potential screening tools to
      identify possibly infected children was examined. RESULTS: Of 767 pediatric
      patients seen in the emergency department during the study period, 312 met
      criteria for review (41%; 95% CI: 37-44%). Four adult patients (0.4%; 95% CI: 0.1
      0.9%) had at least five clinical symptoms, fever, and tachycardia; two of them
      had inhalational anthrax. No pediatric patient presented with five or more
      clinical symptoms. Twelve children (3.9%; 95% CI: 2-6.6%) presented with four
      clinical symptoms; five of the 12 had neither fever nor tachycardia. Children,
      particularly infants and toddlers, presented with nonspecific symptom complexes
      primarily limited to fever, vomiting, cough, and trouble breathing. CONCLUSIONS:
      Existing guidelines are likely to be unreliable as a screening tool for
      inhalational anthrax in children, largely because of the children's inability to
      adequately communicate a suggestive symptom complex.

PMID- 17437351
TI  - Regional approaches to hospital preparedness.
AB  - This article describes issues related to the engagement of hospitals and other
      community partners in a coordinated regional healthcare preparedness and response
      effort. The report is based on interviews with public health and hospital
      representatives from 13 regions or states across the country. It aims to identify
      key ingredients for building successful regional partnerships for healthcare
      preparedness as well as critical challenges and policy and practical
      recommendations for their development and sustainability.

PMID- 17437352
TI  - Regulating biorisks: developing a coherent policy logic (part II).
AB  - This is the second of two articles that empirically details the working practices
      of regulators charged with overseeing biological research. The first article
      considered how regulators from the Biological Agents Unit of the UK Health and
      Safety Executive went about implementing the British legislation controlling work
      with biological agents and genetically modified organisms prior to the terrorist
      attacks of 11 September 2001 and the ensuing anthrax letters in the U.S. This
      second article continues the investigation of the Biological Agents Unit's
      working practices by considering how its activities have changed and adapted to
      the new, post-9/11 policy and regulatory environment. The main argument put
      forward in the articles is that an understanding of the implementation processes-
      that is, the strategies adopted by regulatory agencies and the styles employed by
      agency regulators in their interactions with those regulated--is critical to
      developing a coherent policy logic for the emerging regulatory regime around
      biorisks.

PMID- 17437353
TI  - Biosecurity in Scandinavia.
AB  - This article investigates the extent to which biosecurity measures are recognized
      and have been implemented in the Nordic countries, in the absence of formalized
      security standards and legislation. Two trials were undertaken: first, a broad
      combined biosafety and biosecurity questionnaire survey of the Nordic countries,
      and, second, a focused on-site audit of 22 facilities, with 94 laboratories, in
      Denmark. Both trials indicated that external security had been partially
      implemented but that little attention had been paid to internal security and the
      establishment of biosecurity. It was demonstrated that the backgrounds and
      identities of insiders were rarely checked and that they could have gained access
      to both pathogen inventory lists and freezers in many facilities. In 81% of
      pathogen-containing facilities, pathogens were not routinely and centrally
      accounted for. The authors recommend the establishment of a legal framework
      congruent with international standards and obligations; novel governmental
      national biosecurity authorities, requiring a fusion of both microbiological and
      technical expertise and legislative powers; and the formulation of a new code of
      conduct termed "Good Biosecurity Practice."

PMID- 17437354
TI  - Passage of S. 3678: the Pandemic and All-Hazards Preparedness Act.

PMID- 17437355
TI  - High-containment biodefense research laboratories: meeting report and center
      recommendations.

PMID- 17437356
TI  - Biocontainment patient care units.

PMID- 17437357
TI  - Engineering adeno-associated virus for one-step purification via immobilized
      metal affinity chromatography.
AB  - Adeno-associated virus (AAV) is a promising vehicle for gene therapy, which will
      rely on the generation of high-titer, high-purity recombinant vectors. However,
      numerous purification protocols can involve challenging optimization or
      scalability issues, and most AAV serotypes do not bind heparin or sialic acid,
      used for AAV2/3 or AAV4/5 purification, requiring the development of new
      chromatography strategies. Immobilized metal affinity chromatography (IMAC)
      allows for robust protein purification via affinity tags such as the
      hexahistidine (His(6)) sequence. Through the combination of a diverse AAV2
      library and rational peptide insertions, we have located an optimal His(6) tag
      insertion site within the viral capsid. This mutant and a related AAV8 variant
      can be purified from clarified cell lysate in a single gravity column step at
      infectious particle yields exceeding 90%. Furthermore, injection of IMAC-purified
      vector into the brain demonstrates that it mediates high-efficiency gene delivery
      in vivo, equivalent to that of wild-type capsid, with minimal immune cell
      activation. This affinity chromatography method may offer advantages in ease of
      purification, final vector purity, and process scalability. Moreover, a combined
      rational design and high-throughput library selection approach can aid in the
      design of enhanced viral gene delivery vectors.

PMID- 17437359
TI  - Warning! Danger Will Robinson! Lyme disease clinical practice guidelines of the
      Infectious Diseases Society of America, activist patients, antitrust law, and
      prosecutorial zeal.

PMID- 17437358
TI  - Noggin inhibits postoperative resynostosis in craniosynostotic rabbits.
AB  - Inhibition of bone formation after surgery to correct craniosynostosis would
      alleviate the need for secondary surgeries and decrease morbidity and mortality.
      This study used a single dose of Noggin protein to prevent resynostosis and
      improve postoperative outcomes in a rabbit model of craniosynostosis.
      INTRODUCTION: Craniosynostosis is defined as the premature fusion of one or more
      of the cranial sutures, which causes secondary deformations of the cranial vault,
      cranial base, and brain. Current surgical intervention involves extirpation of
      the fused suture to allow unrestricted brain growth. However, resynostosis of the
      extirpated regions often occurs. Several bone morphogenetic proteins (BMPs), well
      described inducers of ossification, are involved in bone healing. This study
      tested the hypothesis that a postoperative treatment with Noggin, an
      extracellular BMP inhibitor, can inhibit resynostosis in a rabbit model of human
      familial nonsyndromic craniosynostosis. MATERIALS AND METHODS: Thirty-one New
      Zealand white rabbits with bilateral coronal suture synostosis were divided into
      three groups: (1) suturectomy controls (n = 13); (2) suturectomy with BSA in a
      slow-resorbing collagen vehicle, (n = 8); and (3) suturectomy with Noggin in a
      slow-resorbing collagen vehicle (n = 10). At 10 days of age, a 3 x 15-mm coronal
      suturectomy was performed. The sites in groups 2 and 3 were immediately filled
      with BSA-loaded gel or Noggin-loaded gel, respectively. Serial 3D-CT scan
      reconstructions of the defects and standard radiographs were obtained at 10, 25,
      42, and 84 days of age, and the sutures were harvested for histological analysis.
      RESULTS: Radiographic analysis revealed that Noggin-treated animals had
      significantly greater coronal suture marker separation by 25 days and
      significantly greater craniofacial length at 84 days of age compared with
      controls. 3D-CT analysis revealed that Noggin treatment led to significantly
      greater defect areas through 84 days and to increased intracranial volumes at 84
      days of age compared with other groups. Histological analysis supported CT data,
      showing that the untreated and BSA-treated groups had significant healing of the
      suturectomy site, whereas the Noggin-treated group had incomplete wound healing.
      CONCLUSIONS: These data support our hypothesis that inhibition of BMP activity
      using Noggin may prevent postoperative resynostosis in this rabbit model. These
      findings also suggest that Noggin therapy may have potential clinical use to
      prevent postoperative resynostosis in infants with craniosynostosis.

PMID- 17437360
TI  - Surgical Infection Society-Europe: why do patients die postoperatively?

PMID- 17437361
TI  - Predictors of efficacy and health resource utilization in treatment of
      complicated intra-abdominal infections: evidence for pooled clinical studies
      comparing tigecycline with imipenem-cilastatin.
AB  - BACKGROUND: Duration of intravenous (IV) treatment, surgical/radiologic
      interventions for infection control, and hospital length of stay (LOS) are
      important cost considerations in complicated intra-abdominal infections (cIAIs).
      METHODS: Data were pooled from two multinational, double-blind studies conducted
      in hospitalized adults with cIAIs who were randomized (1:1) to receive
      tigecycline (100 mg IV initial dose then 50 mg IV every 12 h) or imipenem
      cilastatin (500 mg IV every 6 h) for 5 to 14 days in order to assess tigecycline
      safety and efficacy. This report focuses on developing predictors of cure and
      health care resource utilization, including the need for repeat
      surgical/radiologic interventions, duration of IV antibiotic therapy, and
      hospital LOS. Multiple regression models were applied for each of the above
      outcomes, incorporating both baseline and on-treatment potential covariates.
      Logistic modeling was used for categorical outcomes (cure; repeat
      surgical/radiologic interventions) and least squares modeling for continuous
      outcomes (duration of IV antibiotic therapy; LOS). Stepwise selection was used to
      retain only those predictors found to be significant (p < 0.05) independent risk
      factors. RESULTS: The most common causative pathogen was Escherichia coli
      (63.0%), with 63.3% of the patients exhibiting polymicrobial infections. The most
      common cIAI diagnosis was complicated appendicitis (51.9%). Lack of clinical cure
      (+ 6.1 days; p < 0.0001), perforation of the intestine (+3.7 days; p < 0.0001),
      an Acute Physiology and Chronic Health Evaluation (APACHE) score >15 (+3.1 days;
      p=0.039), abnormal plasma sodium concentration (+3.7 days; p=0.026), and repeat
      surgical/radiologic intervention (+2.2 days; p=0.0097) were identified as key
      risk factors for longer LOS. Inadequate source control was associated with
      reduced odds of cure, longer IV treatment duration (+1.5 days; p=0.007), and
      longer LOS. The treatment groups did not differ in terms of LOS, IV treatment
      duration, or clinical cure. CONCLUSION: Tigecycline was similar to imipenem
      cilastatin in terms of both efficacy and health resource utilization. Risk
      factors identified in this study for both outcome measures are offered as support
      for guiding clinical practice.

PMID- 17437362
TI  - Inguinal lymph node biopsy in patients infected with the human immunodeficiency
      virus is safe.
AB  - BACKGROUND AND PURPOSE: The incidence of postoperative complications in human
      immunodeficiency virus (HIV)-infected patients remains controversial. Published
      data suggest that these patients are at higher risk for postoperative surgical
      site infections (SSIs) than are uninfected patients if the site is contaminated.
      To determine the incidence of postoperative SSI in HIV-infected patients
      undergoing aseptic surgery at uncontaminated sites, we performed a prospective
      case series analysis. We hypothesized that the rate of postoperative SSI would be
      low for this aseptic procedure, irrespective of CD4(+) lymphocyte counts.
      Additionally, we monitored the rates of other complications, namely, hematoma,
      dorsal vein thrombosis, epididymitis, lymphocele, and suture extrusion. METHODS:
      From May 1, 2000, through January 31, 2006, we performed 137 sterile inguinal
      lymph node biopsies in 44 HIV-infected patients as part of a funded study
      evaluating the role of peripheral lymphatic tissue in the pathophysiology of HIV
      infection. Postoperatively, we followed all patients for a minimum of 30 days.
      RESULTS: Postoperatively, we noted one instance each (0.7%) of infection, dorsal
      vein thrombosis with epididymitis (0.7%), and lymphocele and two cases each
      (1.4%) of hematoma and suture extrusion. The CD4(+) count at the time of biopsy
      did not correlate with postoperative complications. CONCLUSIONS: Inguinal lymph
      node biopsy in HIV-infected patients is safe, irrespective of CD4(+) lymphocyte
      count.

PMID- 17437363
TI  - Tissue and fluid penetration of garenoxacin in surgical patients.
AB  - BACKGROUND AND PURPOSE: Garenoxacin is a novel des-F(6)-quinolone that exhibits
      broad-spectrum activity against a wide range of aerobic and anaerobic pathogens
      of clinical importance. This study examined the penetration of garenoxacin into
      sinus mucosa, incisional skin, subcutaneous tissue, bile, adipose tissue,
      striated muscle, bone, gallbladder wall, liver, small and large bowel mucosa, and
      mesenteric lymph nodes relative to the plasma concentration after an oral 600 mg
      dose. METHODS: A series of 30 patients, ages 20 to 83 years, undergoing elective
      surgery were enrolled. Patients received a single 600 mg oral dose of garenoxacin
      before surgery. Blood and tissue specimens were collected at surgery 3-5 h post
      dose, and garenoxacin concentrations were determined using validated liquid
      chromatography/tandem mass spectrometry assays designed specifically for each
      tissue and biofluid. RESULTS: The mean plasma or bile (mcg/mL) and tissue (mcg/g)
      concentrations ( +/- standard deviation) were plasma 5.71 +/- 3.44, bile 7.59 +/-
      9.96, adipose tissue 0.90 +/- 0.54, subcutaneous tissue 1.19 +/- 1.23, incisional
      skin 3.06 +/- 1.74, striated muscle 3.92 +/- 2.54, bone 2.82 +/- 2.42, sinus
      mucosa 5.26 +/- 3.84, liver 1.84 +/- 0.75, gallbladder 11.59 +/- 11.94, large
      intestine 12.13 +/- 9.34, small intestine 15.66 +/- 19.20, and mesenteric lymph
      node 3.10 +/- 2.44. CONCLUSION: After a single 600 mg oral dose, garenoxacin
      penetrates well into selected tissues and fluids. In addition, the tissue and
      fluid concentrations at 3-5 hours post-dose exceeded the minimum inhibitory
      concentration-90% of most targeted pathogens, suggesting that garenoxacin would
      be effective in the treatment of sinus, skin and skin structure, and intra
      abdominal infections.

PMID- 17437364
TI  - Addition of vasopressin to norepinephrine as independent predictor of mortality
      in patients with refractory septic shock: an observational study.
AB  - OBJECTIVE: To identify predictors of 28-day mortality among patients with
      refractory septic shock treated with norepinephrine with or without vasopressin.
      DESIGN: Prospective observational cohort study. SETTING: A 1,200-bed academic
      medical center. PATIENTS: One hundred thirty-seven patients with septic shock
      treated with norepinephrine with or without vasopressin. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: The 28-day mortality rate was 37.2% (n = 51). By
      multivariate analysis, significant predictors of death were norepinephrine plus
      vasopressin administration (adjusted odds ratio [AOR], 13.96; 95% confidence
      interval [CI] 6.47, 30.08; p = 0.001), lack of goal-directed fluid administration
      during initial resuscitation (AOR 15.82; 95% CI 6.16, 40.61; p = 0.003),
      inappropriate initial antimicrobial therapy (AOR 8.95; 95% CI 2.93, 27.33; p =
      0.05), and higher Acute Physiology and Chronic Health Evaluation (APACHE) II
      score (AOR 1.14; 95% CI 1.07, 1.21; p = 0.033). Patients who received
      norepinephrine plus vasopressin (n = 68) had a significantly higher mortality
      rate than patients managed with norepinephrine alone (n = 69) 28 days after the
      initiation of vasopressors (54.4% vs. 20.3%; p < 0.001). This finding was
      confirmed in patients matched optimally across treatment groups. CONCLUSIONS: Our
      study found an association between the use of norepinephrine plus vasopressin and
      28-day mortality in refractory septic shock. In view of its known mechanism of
      action, vasopressin contributed to this excess mortality. Further recommendations
      regarding the use of vasopressin await the results of large randomized trials
      evaluating its efficacy and safety for septic shock.

PMID- 17437365
TI  - In vitro antibacterial efficacy of MONOCRYL plus antibacterial suture
      (Poliglecaprone 25 with triclosan).
AB  - BACKGROUND: This study evaluated the in vitro efficacy of poliglecaprone 25
      suture with triclosan against gram-positive and gram-negative bacteria. METHODS:
      Poliglecaprone 25 sutures with and without triclosan were tested for in vitro
      efficacy against Staphylococcus aureus, methicillin-resistant Staphylococcus
      aureus (MRSA), Staphylococcus epidermidis, methicillin-resistant Staphylococcus
      epidermidis (MRSE), Klebsiella pneumoniae, and Escherichia coli by a zone of
      inhibition assay. The suture also was tested against Escherichia coli in a
      colonization assay in a dynamic model simulating in vivo conditions. An in vitro
      triclosan diffusion assay and a sustained efficacy assay were performed by
      concurrent high-performance liquid chromatography and zone of inhibition assay.
      To assess stability, antibacterial efficacy testing was performed on samples held
      more than five months at elevated temperature. RESULTS: Poliglecaprone 25 suture
      with triclosan demonstrated significant in vitro efficacy against a range of
      bacteria. The suture sustained in vitro efficacy for 11 days, corresponding to
      the in vitro triclosan diffusion profile. CONCLUSION: Triclosan reduced in vitro
      colonization of poliglecaprone 25 suture by several strains of bacteria compared
      with untreated control sutures.

PMID- 17437366
TI  - In vivo antibacterial efficacy of MONOCRYL plus antibacterial suture
      (Poliglecaprone 25 with triclosan).
AB  - BACKGROUND: This study evaluated the ability of poliglecaprone 25 suture with
      triclosan to inhibit bacterial colonization by Escherichia coli and
      Staphylococcus aureus in mouse and guinea pig models. METHODS: Test and control
      sutures (3-4 cm) were implanted subcutaneously in the dorsal-lateral regions
      (control on the left side, test on the right side, approximately 3-5 cm apart) in
      10 female Hartley guinea pigs (300-400 g) and 10 Swiss Webster mice (20-35 g) via
      a 20-gauge catheter. The test material was poliglecaprone 25 suture with
      triclosan (2-0, undyed), and the control material was poliglecaprone 25 suture (2
      0, undyed). In the guinea pig model, each implantation site was challenged
      directly with 4x10(5) colony-forming units (cfu) of S. aureus, whereas in the
      mouse model, each implantation site was challenged directly with 1.3x10(7) cfu of
      E. coli through an indwelling catheter. At 48 h post-implantation, the control
      and test sutures were explanted, and bacterial enumeration was performed.
      RESULTS: There was a significant difference (p < 0.05) in the number of bacteria
      recovered in the study groups 48 h post-implantation. Poliglecaprone 25 suture
      with triclosan produced a 3.4-log reduction in S. aureus and a 2-log reduction in
      E. coli compared with standard poliglecaprone 25 suture without triclosan under
      the same challenge conditions. The difference between the study groups in the
      number of bacteria recovered was significant (p < 0.05). CONCLUSION:
      Poliglecaprone 25 suture with triclosan inhibited bacterial colonization of the
      suture compared with untreated suture after direct in vivo challenge with S.
      aureus and E. coli in animal models.

PMID- 17437367
TI  - Evaluating empiric treatment options for secondary peritonitis using
      pharmacodynamic profiling.
AB  - BACKGROUND: Selecting an appropriate agent for empiric antibiotic therapy for
      secondary peritonitis is challenging. The pathogens responsible, aerobic gram
      negative bacilli in particular, are becoming more resistant to antibiotics. The
      purpose of this study was to predict the ability of common antimicrobial regimens
      to achieve optimal pharmacodynamic exposure against aerobic bacteria implicated
      in secondary peritonitis, while considering current national resistance trends.
      METHODS: Monte Carlo simulation was used to model pharmacodynamic endpoints and
      compare the cumulative fraction of response (CFR) for imipenem-cilastatin,
      meropenem, ertapenem, piperacillin/tazobactam, ceftazidime, ceftriaxone,
      ciprofloxacin, and levofloxacin against isolates of species associated with
      secondary peritonitis. Minimum inhibitory concentration (MIC) distributions for
      isolates collected in North America were obtained from the 2004 MYSTIC database.
      Pharmacokinetic parameters were derived from the literature; the endpoints
      evaluated included free drug time above the MIC (fT(>MIC)) and the area under the
      concentration-time curve to MIC ratio (AUC:MIC). RESULTS: The simulation
      predicted that several compounds would have a superior probability of providing
      appropriate coverage of aerobic bacteria: Imipenem-cilastatin (98.6% CFR at 1 g
      q8h), meropenem (98.2% CFR at 1 g q8h), ertapenem (91.7% CFR at 1 g q24h),
      piperacillin/ tazobactam (93.7% CFR at 3.375 g q6h), ceftazidime (91.1% CFR at 2
      g q8h), and cefepime (92.9% CFR at 1 g q12h and 95.8% CFR at 2 g q12h).
      Ceftriaxone, ciprofloxacin, and levofloxacin exhibited CFRs < 82%. CONCLUSIONS:
      Considering contemporary susceptibility data for aerobic bacteria, monotherapy
      with any of the three carbapenems or piperacillin/tazobactam 3.375 g q6h would
      provide optimal exposure for the pathogens commonly encountered in secondary
      peritonitis. Cefepime (in combination with metronidazole to provide anti
      anaerobic coverage) also would be an acceptable choice, as would ceftazidime
      given at 2 g q8h (again in combination with metronidazole). Despite the
      popularity of combination therapy based on ciprofloxacin, levofloxacin, or
      ceftriaxone with metronidazole, these choices appear to be inferior to the other
      options because of emerging antibiotic resistance, particularly in E. coli.

PMID- 17437368
TI  - Klebsiella pneumoniae necrotizing fasciitis and septic arthritis: an appearance
      in the Western hemisphere.
AB  - BACKGROUND: Necrotizing fasciitis caused by Klebsiella pneumoniae is rare, with
      11 documented cases in the literature, all occurring in Asia and the Middle East.
      These reports have become more frequent in recent years in association with the
      emergence of the highly virulent K1 capsular serotype of Klebsiella. We report a
      case of Klebsiella necrotizing fasciitis and con-current septic arthritis in the
      Western hemisphere. METHODS: Case report and review of the literature. RESULTS:
      Our patient, a 50-year-old Cambodian man with advanced hepatitis B-associated
      cirrhosis, who had last visited an endemic area six months prior to presentation,
      was hospitalized after several days of left knee and thigh pain. He was
      hypotensive, tachycardic, and bacteremic with K. pneumoniae. A computed
      tomography scan showed gas in the tissues of the thigh and left knee joint.
      Despite aggressive surgical debridement and antibiotic therapy, the patient died
      on day three. Serotyping of blood, wound, and synovial cultures revealed K1-type
      K. pneumoniae. CONCLUSIONS: Although K. pneumoniae is common, monomicrobial
      necrotizing fasciitis and septic arthritis caused by this pathogen has not been
      reported previously outside Asia, where it is rare. The appearance of this
      infection in the Western hemisphere may reflect geographic spread of the
      aggressive K1 phenotype. Physicians treating patients with symptoms and signs of
      necrotizing fasciitis or septic arthritis, particularly in the setting of
      underlying chronic illness or recent travel to Asia, should consider K.
      pneumoniae as a potential cause and treat accordingly.

PMID- 17437369
TI  - Inguinal site infection as a rare cause of secondary peritonitis: report of a
      case.
AB  - BACKGROUND: Many rare conditions may cause secondary peritonitis. Injection site
      infection as a primary source of peritonitis has not been reported. METHODS: Case
      report and review of the pertinent English-language literature. RESULTS: We
      describe a 39-year-old intravenous drug user who presented with peritonitis.
      During the surgical exploration, all abdominal organs were intact, but there was
      an orifice in the pelvic peritoneum that was related to an inguinal site
      infection. Cultures of both the inguinal area and the peritoneal cavity discharge
      revealed Staphylococcus aureus. CONCLUSIONS: Physicians should be aware of
      secondary peritonitis induced by self-injection of illicit substances in
      proximity to the peritoneal envelope.

PMID- 17437370
TI  - Antibiotic use in the treatment of soft tissue abscesses: a survey of current
      practice.

PMID- 17437378
TI  - You can get here from there.
AB  - During one of the several unsuccessful admission interviews I had before finally
      being admitted to a graduate program, an interviewer asked me what kind of
      research I would like to do as a psychologist. "I plan to validate the Rorschach"
      was my reply. "And what will you do if you find the Rorschach isn't valid?" was
      the interviewer's next question. I don't recall my answer but it was obviously
      inadequate because such an unlikely possibility hadn't occurred to me, and I
      wasn't admitted to that program. Looking back, it is very clear how one thing led
      to another so that instead of validating the Rorschach, I ended up exploring the
      contribution of genetic factors to stress ulcers in rats and children's
      personality.

PMID- 17437379
TI  - Rorschach test findings at the beginning of treatment and 2 years later, with a
      30-year follow-up.
AB  - In this article, I report a case containing 2 Rorschach assessments-the first
      (R1) 30 years ago at the beginning of a 4-year period of psychotherapy and the
      second (R2) 2 years later. I also recently contacted the patient to obtain
      information about his life during the 26 years since termination. This report
      examines the 2 Rorschach protocols-combining the Comprehensive System (CS; Exner,
      2003) structural summaries with thematic content analysis-in relation to the
      patient's history, treatment, and 30-year outcome. I focus on the change between
      R1 and R2, particularly the shift from an introversive to an ambitent EB and a
      corresponding shift from 6 Y responses on R1 to 6 m responses on R2. In the
      clinical interpretation, I considered these shifts in a context of the patient's
      patterns of managing destabilization and overstimulation.

PMID- 17437380
TI  - Factor analysis of the Dutch-language version of the MCMI-III.
AB  - We analyzed the factor structure of the Dutch-language version of the MCMI-III
      (Millon, Millon, Davis, & Grossman, 2006) using exploratory factor analysis on
      data obtained from a heterogeneous White sample (n = 1,210). We identified 4
      factors: General Maladjustment, Aggression/Social Deviance, Paranoid/Delusional
      Thinking, and Emotional Instability/Detachment. This structure was invariant
      across scale composition (linear dependent vs. independent scales), factor
      analytic method (principal factor vs. principal component solutions), and sample
      characteristics (gender 'male-female' and setting 'clinical-forensic.' Studies
      that have used previous MCMI (Millon, 1969/1983b) versions have also found 4
      similar factors, whereas studies that have used the American version of the MCMI
      III have only found 3 factors. However, differences between the Dutch and
      American version were completely determined by factor analytic decisions. The
      factor structure of the MCMI-III appeared to be cross-culturally invariant.

PMID- 17437381
TI  - Maladaptive correlates of the failure to forgive self and others: further
      evidence for a two-component model of forgiveness.
AB  - In a sample composed of 162 young adults, we examined the generalizability of an
      orthogonal, 2-component model of forgiveness previously reported by Ross,
      Kendall, Matters, Rye, and Wrobel (2004). Furthermore, we examined the
      relationship of these two components with maladaptive personality characteristics
      as measured by the Schedule for Nonadaptive and Adaptive Personality (SNAP;
      Clark, 1993), with an emphasis on Five-factor model markers of personality. Using
      multiple measures of forgiveness, principal components analysis supported a 2
      component model representing self-forgiveness and other forgiveness. Despite the
      independence of self-forgiveness and other forgiveness, zero order correlations
      with SNAP scales supported convergent more than discriminant validity. In
      contrast, hierarchical multiple regression analyses emphasized the discriminant
      validity of self-forgiveness and other forgiveness. Among indices of Neuroticism,
      Extraversion, and Agreeableness, Negative Temperament (+) was the sole predictor
      of self-forgiveness. In contrast, Positive Temperament (+), Aggression (-), and
      Histrionic PD (-) were most associated with other forgiveness. Overall, these
      findings support the validity of these factors and highlight the importance of
      self-forgiveness in clinical assessment.

PMID- 17437382
TI  - An analysis of a cross-cultural personality inventory: the IPIP Big-Five factor
      markers in Croatia.
AB  - In this article, we describe the factor structure in both self-reports and peer
      ratings of the items in a cross-cultural Big-Five inventory in Croatia. Using 2
      versions of an inventory developed from the International Personality Item Pool
      (IPIP; Goldberg, 1999), this is one of the first cross-national analyses of these
      IPIP measures. A large sample of university students (N = 519) used the
      translated Croatian version of the 100-item IPIP Big Five inventory to describe
      themselves, and they were also described by 515 of their acquaintances on the
      same instrument. In separate analyses of both self-reports and peer ratings, the
      100-item and 50-item versions of these IPIP measures showed clear Five-factor
      orthogonal structures that were nearly identical to the American structure. These
      factors were strongly related on a one-to-one basis with those derived from a
      Croatian translation of Goldberg's (1992) bipolar rating scales.

PMID- 17437383
TI  - MMPI-2 profiles of women with eating disorders in a Dutch day treatment sample.
AB  - In this study, we examined the MMPI-2 (Butcher, Dahlstrom, Graham, Tellegen, &
      Kaemmer, 1989) profiles of 324 Dutch patients with eating disorders at an eating
      disorder day treatment program. We studied the MMPI-2 profiles in 5 diagnostic
      eating disorder groups. All diagnostic subgroups showed high mean elevations of
      the T scores on the same 6 or 7 scales. Remarkable similarities existed between
      the mean profile configurations. The MMPI-2 distinguished especially in that
      patients with restricting anorexia nervosa scored lower on one Validity scale
      (F), two Clinical scales (1 and 2) and several Supplementary and Content scales
      of the MMPI-2 compared to the other groups. Only on the validity Scale L did they
      score higher. The MMPI-2 also distinguished patients with the bulimia nervosa
      purging type who scored higher on Scale 9 and different on several Content and
      Supplementary scales. We discuss results with regard to other studies of MMPI
      (Hathaway & McKinley, 1983) and MMPI-2 profiles of women with anorexia nervosa,
      bulimia nervosa, and eating disorder not otherwise specified in inpatient and
      outpatient settings.

PMID- 17437384
TI  - The Experiences in Close Relationship Scale (ECR)-short form: reliability,
      validity, and factor structure.
AB  - We developed a 12-item, short form of the Experiences in Close Relationship Scale
      (ECR; Brennan, Clark, & Shaver, 1998) across 6 studies. In Study 1, we examined
      the reliability and factor structure of the measure. In Studies 2 and 3, we cross
      validated the reliability, factor structure, and validity of the short form
      measure; whereas in Study 4, we examined test-retest reliability over a 1-month
      period. In Studies 5 and 6, we further assessed the reliability, factor
      structure, and validity of the short version of the ECR when administered as a
      stand-alone instrument. Confirmatory factor analyses indicated that 2 factors,
      labeled Anxiety and Avoidance, provided a good fit to the data after removing the
      influence of response sets. We found validity to be equivalent for the short and
      the original versions of the ECR across studies. Finally, the results were
      comparable when we embedded the short form within the original version of the ECR
      and when we administered it as a stand-alone measure.

PMID- 17437385
TI  - Capturing the four-factor structure of psychopathy in college students via self
      report.
AB  - A number of self-report psychopathy scales have been used successfully in both
      clinical and nonclinical settings. However, their factor structure does not
      adequately capture the four factors (Interpersonal, Affective, Lifestyle, and
      Antisocial) recently identified in the Psychopathy Checklist-Revised (PCL-R;
      Hare, 2003) and related measures. This deficit was addressed by upgrading the
      Self Report Psychopathy Scale (SRP-II; Hare, Hemphill, & Harpur, 1989). In Study
      1 (N = 249), an exploratory factor analysis of this experimental version revealed
      oblique factors similar to those outlined by Hare (2003). In Study 2 (N = 274),
      confirmatory factor analysis (CFA) confirmed this structure, that is, four
      distinct but intercorrelated factors. The factors exhibited appropriate construct
      validity in a nomological network of related personality measures. Links with
      self-reports of offensive activities (including entertainment preferences and
      behavior) also supported the construct validity of the oblique four-factor model.

PMID- 17437386
TI  - Bandwidth and fidelity on the NEO-Five Factor Inventory: replicability and
      reliability of Saucier's (1998) item cluster subcomponents.
AB  - Many users of the NEO-Five Factor Inventory (NEO-FFI; Costa & McCrae, 1992) are
      unaware that Saucier (1998) developed item cluster subcomponents for each broad
      domain of the instrument similar to the facets of the Revised NEO Personality
      Inventory (Costa & McCrae, 1992). In this study, I examined the following: the
      replicability of the subcomponents in young adult university and middle-aged
      community samples; whether item keying accounted for additional covariance among
      items; subcomponent correlations with a measure of socially desirable responding;
      subcomponent reliabilities; and subcomponent discriminant validity with respect
      to age-relevant criterion items expected to reflect varying associations with
      broad and narrow traits. Confirmatory factor analyses revealed that all
      subcomponents were recoverable across samples and that the addition of method
      factors representing positive and negative item keying improved model fit. The
      subcomponents correlated no more with a measure of socially desirable responding
      than their parent domains and showed good average reliability. Correlations with
      criterion items suggested that subcomponents may prove useful in specifying which
      elements of NEO-FFI domains are more or less related to variables of interest. I
      discuss their use for enhancing the precision of findings obtained with NEO-FFI
      domain scores.

PMID- 17437387
TI  - Validation of the SASB Introject Surface in a Norwegian clinical and nonclinical
      sample.
AB  - In this study, we examined the reliability and construct validity of the
      Structural Analysis of Social Behavior Introject Surface, Intrex long form A
      (SASB-IS; Benjamin, 1995) in 2 Norwegian samples. The fit of the 8 SASB-IS scales
      to the structural requirements of a circumplex model with relaxed equal spacing
      constraints was reasonably good in an outpatient sample, but poor in a normal
      reference sample. The deviations from the equal spacing based on an ideal
      circumplex model, however, seem to have minimal implications for the utility of
      the instrument in clinical assessment. The reliability of the SASB-IS was
      acceptable on most scales, but two scales had unacceptable low reliability.
      Correspondence with external criteria supported the validity of the SASB-IS in
      both samples. Profile patterns related to different segments of the introject
      circumplex model were systematically related to severity of psychopathology:
      Hostile and accepting patterns of self-relatedness formed polar opposites;
      control patterns and intermediate patterns gave intermediate pathology scores.

PMID- 17437388
TI  - Dimensionality of the Rosenberg Self-Esteem Scale and its relationships with the
      Three-and the Five-factor personality models.
AB  - We investigated the dimensionality of the French version of the Rosenberg Self
      Esteem Scale (RSES; Rosenberg, 1965) using confirmatory factor analysis. We
      tested models of 1 or 2 factors. Results suggest the RSES is a 1-dimensional
      scale with 3 highly correlated items. Comparison with the Revised NEO-Personality
      Inventory (NEO-PI-R; Costa, McCrae, & Rolland, 1998) demonstrated that
      Neuroticism correlated strongly and Extraversion and Conscientiousness moderately
      with the RSES. Depression accounted for 47% of the variance of the RSES. Other
      NEO-PI-R facets were also moderately related with self-esteem.

PMID- 17437390
TI  - Disaster surge planning in Australia: measuring the immeasurable.

PMID- 17437391
TI  - Inhaled insulin: where are we and where might we go?

PMID- 17437392
TI  - The Surge Capacity for People in Emergencies (SCOPE) study in Australasian
      hospitals.
AB  - OBJECTIVES: To measure physical assets in Australasian hospitals required for the
      management of mass casualties as a result of terrorism or natural disasters.
      DESIGN AND SETTING: A cross-sectional survey of Australian and New Zealand
      hospitals. PARTICIPANTS: All emergency department directors of Australasian
      College for Emergency Medicine (ACEM)-accredited hospitals, as well as private
      and non-ACEM accredited emergency departments staffed by ACEM Fellows in
      metropolitan Sydney. MAIN OUTCOME MEASURES: Numbers of operating theatres,
      intensive care unit (ICU) beds and x-ray machines; state of preparedness using
      benchmarks defined by the Centers for Disease Control and Prevention in the
      United States. RESULTS: We found that 61%-82% of critically injured patients
      would not have immediate access to operative care, 34%-70% would have delayed
      access to an ICU bed, and 42% of the less critically injured would have delayed
      access to x-ray facilities. CONCLUSIONS: Our study demonstrates that physical
      assets in Australasian public hospitals do not meet US hospital preparedness
      benchmarks for mass casualty incidents. We recommend national agreement on
      disaster preparedness benchmarks and periodic publication of hospital performance
      indicators to enhance disaster preparedness.

PMID- 17437393
TI  - Does a diagnosis of the metabolic syndrome provide additional prediction of
      cardiovascular disease and total mortality in the elderly? The Dubbo Study.
AB  - OBJECTIVE: To assess whether a diagnosis of the metabolic syndrome (MetS)
      improves the prediction of cardiovascular disease or total mortality beyond that
      already provided by conventional risk factors. DESIGN AND SETTING: A longitudinal
      cohort study conducted in Dubbo, New South Wales. PARTICIPANTS: 2805 men and
      women aged 60 years and older living in the community, first assessed in 1988
      1989 and followed for 16 years. MAIN OUTCOME MEASURES: Coronary heart disease
      (CHD) events, ischaemic stroke events, and total mortality. RESULTS: MetS was
      present in 31% of men and 34% of women. Crude CHD, ischaemic stroke, and total
      mortality rates were higher in the presence of MetS in men and women. In
      proportional hazards models that included conventional risk factors, but excluded
      variables used to define the presence of MetS, MetS was a significant predictor
      of CHD, stroke and total mortality. In men, the respective hazard ratios were
      1.64 (95% CI, 1.37-1.96), 1.31 (95% CI, 0.97-1.77), and 1.53 (95% CI, 1.30-1.79).
      In women, the respective hazard ratios were 1.70 (95% CI, 1.43-2.02), 1.37 (95%
      CI, 1.04-1.82), and 1.35 (95% CI, 1.15-1.59). The use of MetS variables on an
      ordinal scale produced broadly similar conclusions. CONCLUSIONS: A diagnosis of
      MetS provides additional prediction of CHD events, stroke events, and total
      mortality beyond that provided by other conventional risk factors.

PMID- 17437394
TI  - Cancer screening in Queensland men.
AB  - OBJECTIVES: To describe the self-reported use of prostate specific antigen (PSA)
      tests, faecal occult blood tests (FOBTs), and whole-body skin examinations among
      Queensland men, reasons for use, and the personal characteristics of men
      undergoing the tests for cancer screening. SETTING AND DESIGN: Data were obtained
      from the Queensland Cancer Risk Study (QCRS), a population-based telephone survey
      conducted in 2004, which used random sampling stratified by age, sex, and
      geographic location. PARTICIPANTS: All men aged 50-75 years who participated in
      the QCRS (n = 2336). MAIN OUTCOME MEASURES: Use of PSA test, FOBT, or whole-body
      skin examination, specifically as a screening procedure; the probability of being
      screened; and associations with sociodemographic factors, risk behaviour, and
      cancer experience. RESULTS: More than a third of men reported never having been
      screened for prostate, colorectal, or skin cancer. Of those who had been
      screened, the odds of PSA testing being reported were more than two times greater
      than the odds of whole-body skin examination (adjusted odds ratio [OR], 2.54; 95%
      CI, 1.49-4.32), and the odds of reporting an FOBT were less (adjusted OR, 0.48;
      95% CI, 0.22-1.04). Men who participated in cancer screening tended to be older,
      white, living with a partner, and to have private health insurance. Smokers were
      less likely to be screened with any of the three screening tests. CONCLUSIONS: Of
      these three cancer screening tests, the FOBT has the best evidence for reducing
      mortality and yet is the least frequently used by Queensland men. There are
      disparities in reported screening prevalence between the specific tests and
      across certain population subgroups.

PMID- 17437395
TI  - Trends in hospital admissions and mortality from asthma and chronic obstructive
      pulmonary disease in Australia, 1993-2003.
AB  - OBJECTIVE: To examine evolving changes in asthma and chronic obstructive
      pulmonary disease (COPD) in South Australia and Australia as a whole from the
      perspective of hospital admissions, ventilatory support and mortality data.
      DESIGN: Retrospective analyses, for the period 1993-2003, of hospital separations
      data from the Australian Institute of Health and Welfare and the Integrated South
      Australian Activity Collection, and mortality data from the Australian Bureau of
      Statistics and South Australian hospital morbidity collection. MAIN OUTCOME
      MEASURES: Hospital separations, ventilatory support episodes, mortality rates,
      burden-of-disease rankings. RESULTS: Between 1993 and 2003, in SA and nationally,
      hospital separations for asthma declined but separations for COPD increased
      significantly. Falling mortality rates from asthma in both men and women, and
      from COPD in men, contrast with increasing rates of COPD-related hospitalisation
      and mortality in women. CONCLUSIONS: Hospital admissions and mortality associated
      with asthma have fallen. Admission rates for COPD are declining for men, but
      there is no indication that admission rates for women have reached a peak. There
      is a need for higher prioritisation of COPD, including policies to reduce smoking
      in women, and medical practice initiatives to support primary and secondary
      prevention, pulmonary rehabilitation and appropriate drug therapies.

PMID- 17437396
TI  - Amoebiasis: current status in Australia.
AB  - Entamoeba histolytica is one of the most common parasitic infections worldwide,
      infecting about 50 million people and resulting in 40,000-100,000 deaths a year.
      In Australia, people at risk of infection include immigrants, travellers
      returning from countries of high endemicity, Indigenous people, and men who have
      sex with men. Clinical manifestations range from asymptomatic carriage to
      invasive disease. Amoebic colitis and amoebic liver abscess are the most common
      invasive manifestations observed in Australia. Diagnosis depends on a high index
      of suspicion and laboratory investigations. Molecular methods (using the
      polymerase chain reaction) are the most sensitive for identifying and
      differentiating Entamoeba species. Treatment should always include a luminal
      agent to eradicate colonisation, prevent spread and/or reduce the risk of
      invasive disease. Medical therapy can successfully cure invasive disease,
      including amoebic liver abscesses.

PMID- 17437397
TI  - Fatal late-onset ornithine transcarbamylase deficiency after coronary artery
      bypass surgery.

PMID- 17437398
TI  - Reporting units for therapeutic drug monitoring: a correctable source of
      potential clinical error.
AB  - Variation between laboratories and reference sources in the units used for
      reporting pathology results raises the possibility of medical error. Data
      submitted to the RCPA Quality Assurance Programs demonstrate wide variation in
      the units used for reporting therapeutic drug concentrations. This potential
      source of medical error needs to be addressed by all parties involved in
      communicating drug concentrations and providing support information.

PMID- 17437399
TI  - Pseudomonas chloronychia in a patient with nail psoriasis.

PMID- 17437400
TI  - A woman with abnormal ears and an unusual voice.

PMID- 17437401
TI  - On the merits of writing to the next of kin after the death of your patient: an
      Australian perspective.

PMID- 17437402
TI  - Potential impact of AUSFTA on Australia's blood supply.

PMID- 17437403
TI  - Prevocational medical training and the Australian Curriculum Framework for Junior
      Doctors: a junior doctor perspective.

PMID- 17437404
TI  - Medical education registrars: new thoughts on old problems.

PMID- 17437405
TI  - Caspase 3 attenuates XIAP (X-linked inhibitor of apoptosis protein)-mediated
      inhibition of caspase 9.
AB  - During apoptosis, the initiator caspase 9 is activated at the apoptosome after
      which it activates the executioner caspases 3 and 7 by proteolysis. During this
      process, caspase 9 is cleaved by caspase 3 at Asp(330), and it is often inferred
      that this proteolytic event represents a feedback amplification loop to
      accelerate apoptosis. However, there is substantial evidence that proteolysis per
      se does not activate caspase 9, so an alternative mechanism for amplification
      must be considered. Cleavage at Asp(330) removes a short peptide motif that
      allows caspase 9 to interact with IAPs (inhibitors of apoptotic proteases), and
      this event may control the amplification process. We show that, under
      physiologically relevant conditions, caspase 3, but not caspase 7, can cleave
      caspase 9, and this does not result in the activation of caspase 9. An IAP
      antagonist disrupts the inhibitory interaction between XIAP (X-linked IAP) and
      caspase 9, thereby enhancing activity. We demonstrate that the N-terminal peptide
      of caspase 9 exposed upon cleavage at Asp330 cannot bind XIAP, whereas the
      peptide generated by autolytic cleavage of caspase 9 at Asp315 binds XIAP with
      substantial affinity. Consistent with this, we found that XIAP antagonists were
      only capable of promoting the activity of caspase 9 when it was cleaved at
      Asp315, suggesting that only this form is regulated by XIAP. Our results
      demonstrate that cleavage by caspase 3 does not activate caspase 9, but enhances
      apoptosis by alleviating XIAP inhibition of the apical caspase.

PMID- 17437406
TI  - The iron-responsive element (IRE)/iron-regulatory protein 1 (IRP1)-cytosolic
      aconitase iron-regulatory switch does not operate in plants.
AB  - Animal cytosolic ACO (aconitase) and bacteria ACO are able to switch to RNA
      binding proteins [IRPs (iron-regulatory proteins)], thereby playing a key role in
      the regulation of iron homoeostasis. In the model plant Arabidopsis thaliana, we
      have identified three IRP1 homologues, named ACO1-3. To determine whether or not
      they may encode functional IRP proteins and regulate iron homoeostasis in plants,
      we have isolated loss-of-function mutants in the three genes. The aco1-1 and aco3
      1 mutants show a clear decrease in cytosolic ACO activity. However, none of the
      mutants is affected in respect of the accumulation of the ferritin transcript or
      protein in response to iron excess. cis-acting elements potentially able to bind
      to the IRP have been searched for in silico in the Arabidopsis genome. They
      appear to be very rare sequences, found in the 5'-UTR (5'-untranslated region) or
      3'-UTR of a few genes unrelated to iron metabolism. They are therefore unlikely
      to play a functional role in the regulation of iron homoeostasis. Taken together,
      our results demonstrate that, in plants, the cytosolic ACO is not converted into
      an IRP and does not regulate iron homoeostasis. In contrast with animals, the RNA
      binding activity of plant ACO, if any, would be more likely to be attributable to
      a structural element, rather than to a canonical sequence.

PMID- 17437407
TI  - BioClips of symmetric and asymmetric cell division.
AB  - Animations have long been used as tools to illustrate complex processes in such
      diverse fields as mechanical engineering, astronomy, bacteriology and physics.
      Animations in biology hold particular educational promise for depicting complex
      dynamic processes, such as photosynthesis, motility, viral replication and
      cellular respiration, which cannot be easily explained using static two
      dimensional images. However, these animations have often been restrictive in
      scope, having been created for a specific classroom or research audience. In
      recent years, a new type of animation has emerged called the BioClip
      (http://www.bioclips.com) that strives to present science in an interactive
      multimedia format, which is, at once, informative and entertaining, by combining
      animations, text descriptions and music in one portable cross-platform document.
      In the present article, we illustrate the educational value of this new
      electronic resource by reviewing in depth two BioClips our group has created
      which describe the processes of symmetric and asymmetric cell division
      (http://www.wormclassroom.org/cb/bioclip).

PMID- 17437408
TI  - Upregulation of brain expression of P-glycoprotein in MRP2-deficient TR(-) rats
      resembles seizure-induced up-regulation of this drug efflux transporter in normal
      rats.
AB  - PURPOSE: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter
      that is expressed predominantly at the apical domain of hepatocytes but seems
      also to be expressed at the apical membrane of brain capillary endothelial cells
      that form the blood-brain barrier (BBB). MRP2 is absent in the transport
      deficient (TR(-)) Wistar rat mutant, so that this rat strain was very helpful in
      defining substrates of MRP2 by comparing tissue concentrations or functional
      activities of compounds in MRP2-deficient rats with those in transport-competent
      Wistar rats. By using this strategy to study the involvement of MRP2 in brain
      access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a
      substrate for MRP2 in the BBB. However, one drawback of such studies in
      genetically deficient rats is the fact that compensatory changes with
      upregulation of other transporters can occur. This prompted us to study the brain
      expression of P-glycoprotein (Pgp), a major drug efflux transporter in many
      tissues, including the BBB, in TR(-) rats compared with nonmutant (wild-type)
      Wistar rats. METHODS: The expression of MRP2 and Pgp in brain and liver sections
      of TR(-) rats and normal Wistar rats was determined with immunohistochemistry, by
      using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp
      antibody C219, respectively. RESULTS: Immunofluorescence staining with the MRP2
      antibody was found to label a high number of microvessels throughout the brain in
      normal Wistar rats, whereas such labeling was absent in TR(-) rats. TR(-) rats
      exhibited a significant up-regulation of Pgp in brain capillary endothelial cells
      compared with wild-type controls. No such obvious upregulation of Pgp was
      observed in liver sections. A comparable overexpression of Pgp in the BBB was
      obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments
      with systemic administration of the Pgp substrate phenobarbital and the selective
      Pgp inhibitor tariquidar in TR(-) rats substantiated that Pgp is functional and
      compensates for the lack of MRP2 in the BBB. CONCLUSIONS: The data on TR(-) rats
      indicate that Pgp plays an important role in the compensation of MRP2 deficiency
      in the BBB. Because such a compensatory mechanism most likely occurs to reduce
      injury to the brain from cytotoxic compounds, the present data substantiate the
      concept that MRP2 performs a protective role in the BBB. Furthermore, our data
      suggest that TR(-) rats are an interesting tool to study consequences of
      overexpression of Pgp in the BBB on access of drugs in the brain, without the
      need of inducing seizures or other Pgp-enhancing events for this purpose.

PMID- 17437409
TI  - Differential cellular gene expression in ganglioglioma.
AB  - PURPOSE: Gangliogliomas (GGs) are neuronal-glial tumors highly associated with
      epilepsy. We hypothesized that the expression of select gene families including
      neurotransmitter receptor subunits and growth factors would be distinct in
      neurons and astrocytes within GG compared with adjacent cortex and that these
      changes would yield insights into seizure onset and lesion formation. METHODS:
      Candidate gene expression was defined in single immunohistochemically labeled
      neurons and astrocytes microdissected from GG specimens compared with neurons and
      astrocytes microdissected from morphologically intact cortex adjacent to the GG
      or normal control cortex. RESULTS: Differential expression of 16 genes including
      glutamate transporter (EAAC1) and receptor (NMDA2C, mGluR5), growth factor
      (hepatocyte growth factor), and receptor (platelet derived growth factor receptor
      beta, fibroblast growth factor receptor 3) mRNAs was detected in GG neurons
      compared with control neurons. In astrocytes, altered expression of p75NGF,
      mGluR3, TGFbeta3 and Glt-1 mRNAs was detected. Nestin mRNA, a gene that exhibits
      enhanced expression in balloon cell cortical dysplasia, was increased in GG
      neurons. Because of the morphological similarities between GG and cortical
      dysplasia, we show that there is activation of the mTOR cascade in GG as
      evidenced by enhanced expression of phospho-p70S6kinase and phosphoribosomal S6
      proteins. CONCLUSION: We find differential candidate gene expression in neurons
      and astrocytes in GG compared with adjacent cortex and show that there is
      activation of the mTOR pathway. These changes highlight pathways that may be
      pivotal for epileptogenesis and lesion growth.

PMID- 17437410
TI  - Lack of support for a role for RLIP76 (RALBP1) in response to treatment or
      predisposition to epilepsy.
AB  - BACKGROUND: Multidrug transporters are postulated to contribute to antiepileptic
      drug (AED) resistance. The transporter best studied is P-glycoprotein, an ATP
      Binding Cassette (ABC) transporter superfamily member. RLIP76 is suggested to be
      an energy-dependent non-ABC transporter, reducing AED blood-brain barrier
      penetration, with a more important role than P-glycoprotein. Knowledge of which
      transporters may be critical in drug resistance is important for design of
      potential therapies. We tested the hypothesis that RLIP76 mediates AED resistance
      using methods complementary to those in the original report. METHODS: Double
      labeling fluorescent immunohistochemistry localized RLIP76 expression. Population
      genetics was used to explore association of variation in the RLIP76-encoding gene
      with drug-response and epilepsy phenotypes. Comparative protein structure
      modeling and bioinformatic annotation were used to predict RLIP76 structure and
      features. RESULTS: In normal and epileptogenic brain tissue, immunoreactivity for
      RLIP76 was cytoplasmic, with colocalization with a neuronal, but not an
      endothelial, marker. Genotyping of six tagging SNPs, representing common genetic
      variation in RLIP76, in patients with epilepsy responsive (n = 262) or resistant
      (n = 107) to AEDs showed no association with phenotype at any level. RLIP76
      genotypic and haplotypic frequencies in 783 patients with epilepsy and 359
      healthy controls showed no association with epilepsy susceptibility. RLIP76 is
      not predicted to have transmembrane localization or ATPase activity. CONCLUSIONS:
      No support for RLIP76 itself in directly mediating resistance to AEDs nor in
      increasing susceptibility to epilepsy was found. More evidence is required before
      either a role for RLIP76 in drug resistance can be accepted or focus directed
      away from other transporters, such as P-glycoprotein.

PMID- 17437411
TI  - Fetal exposure to GABA-acting antiepileptic drugs generates hippocampal and
      cortical dysplasias.
AB  - PURPOSE: The management of epilepsy during pregnancy entails a number of
      concerns. While seizures may affect adversely maternal and fetal outcome,
      antiepileptic drugs (AEDs) may increase the incidence of congenital abnormalities
      and possibly affect postnatal cognitive development in the offspring.
      Experimental animal studies can aid in assessing teratogenic features associated
      with individual AEDs and/or with seizures, and to identify the mechanisms
      involved. The purpose of this study was to investigate the consequences of
      prenatal exposure to (a) different AEDs and (b) maternal seizures on brain
      maturational processes in rats. METHODS: Pregnant rats received from embryonic
      days 14 to 19 intraperitoneal injections of carbamazepine (20 mg/kg/day),
      vigabatrin (200 mgkg/day), and valproate (100 mg/kg/day) at doses not widely
      different from those used clinically. Pups exposed to AEDs in utero were analyzed
      postnatally. Animals born to "kindled" pregnant animals that had experienced one
      generalized convulsive seizure per day during the same gestational period were
      analyzed in parallel. RESULTS: Prenatal exposure to vigabatrin and valproate,
      which act on GABA signaling, induced hippocampal and cortical dysplasias, which
      were likely to result from a neuronal migration defect and neuronal death. By
      contrast, offspring of rats exposed to carbamazepine (which at the dose used
      produced low plasma concentrations) or to generalized convulsive seizures showed
      no clear-cut evidence of dysplasias. CONCLUSIONS: We suggest that AEDs that
      increase the extracellular concentration of GABA might induce severe neuronal
      migration disorders. Drugs acting through other molecular targets would also
      perturb cortical maturation. The potential clinical relevance of these results
      should be a subject of future research.

PMID- 17437412
TI  - Induction of the Wnt inhibitor, Dickkopf-1, is associated with neurodegeneration
      related to temporal lobe epilepsy.
AB  - Inhibition of the Wnt pathway by the secreted glycoprotein, Dickkopf-1 (Dkk-1)
      has been related to processes of excitotoxic and ischemic neuronal death. We now
      report that Dkk-1 is induced in neurons of the rat olfactory cortex and
      hippocampus degenerating in response to seizures produced by systemic injection
      of kainate (12 mg/kg, i.p.). There was a tight correlation between Dkk-1
      expression and neuronal death in both regions, as shown by the different
      expression profiles in animals classified as "high" and "low" responders to
      kainate. For example, no induction of Dkk-1 was detected in the hippocampus of
      low responder rats, in which seizures did not cause neuronal loss. Induction of
      Dkk-1 always anticipated neuronal death and was associated with a reduction in
      nuclear levels of beta-catenin, which reflects an ongoing inhibition of the
      canonical Wnt pathway. Intracerebroventricular injections of Dkk-1 antisense
      oligonucleotides (12 nmol/2 microL) substantially reduced kainate-induced
      neuronal damage, as did a pretreatment with lithium ions (1 mEq/kg, i.p.), which
      rescue the Wnt pathway by acting downstream of the Dkk-1 blockade. Taken
      collectively, these data suggest that an early inhibition of the Wnt pathway by
      Dkk-1 contributes to neuronal damage associated with temporal lobe epilepsy. We
      also examined Dkk-1 expression in the hippocampus of epileptic patients and their
      controls. A strong Dkk-1 immunolabeling was found in six bioptic samples and in
      one autoptic sample from patients with mesial temporal lobe epilepsy associated
      with hippocampal sclerosis. Dkk-1 expression was undetectable or very low in
      autoptic samples from nonepileptic patients or in bioptic samples from patients
      with complex partial seizures without neuronal loss and/or reactive gliosis in
      the hippocampus. Our data raise the attractive possibility that drugs able to
      rescue the canonical Wnt pathway, such as Dkk-1 antagonists or inhibitors of
      glycogen synthase kinase-3beta, reduce the development of hippocampal sclerosis
      in patients with temporal lobe epilepsy.

PMID- 17437413
TI  - A multicenter study of BRD2 as a risk factor for juvenile myoclonic epilepsy.
AB  - PURPOSE: Although complex idiopathic generalized epilepsies (IGEs) are recognized
      to have a significant genetic component, as yet there are no known common
      susceptibility variants. It has recently been suggested that variation in the
      BRD2 gene confers increased risk of juvenile myoclonic epilepsy (JME), which
      accounts for around a quarter of all IGE. Here we examine the association between
      the candidate causal SNP (the promoter variant rs3918149) and JME in five
      independent cohorts comprising in total 531 JME cases and 1,390 healthy controls.
      METHODS: The strongest candidate causal variant from the original report
      (rs3918149) was genotyped across all five cohorts. In an effort to identify novel
      candidate causal polymorphisms, previously unscreened regions of UTR were
      resequenced. RESULTS: We observed a significant effect in a small sample
      recruited in Britain (genotype p = 0.001, allele p = 0.001), a borderline
      significant effect in a sample recruited in Ireland and no association in larger
      samples of German, Australian, and Indian populations. There was no association
      with other common forms of epilepsy or any other clear candidate casual variants
      in or near the BRD2 region. CONCLUSIONS: The replication of an effect in the
      British cohort and suggestive evidence from that recruited in Ireland but lack of
      replication from the larger German, Australian, and Indian cohorts is surprising
      and difficult to explain. Further replication in carefully matched populations is
      required. Results presented here do not, however, support a strong effect for
      susceptibility to JME across populations of European descent.

PMID- 17437414
TI  - Postictal single-cell firing patterns in the hippocampus.
AB  - PURPOSE: Patients with epilepsy have varying degrees of postictal impairment
      including confusion and amnesia. This impairment adds substantially to the
      disease burden of epilepsy. However, the mechanism responsible for postictal
      cognitive impairment is unclear. The purpose of this study was to study single
      cell firing patterns in hippocampal cells after spontaneous seizures in rats
      previously subjected to status epilepticus. METHODS: In this study, we monitored
      place cells and interneurons in the CA1 region of the hippocampus before and
      after spontaneous seizures in six epileptic rats with a history of status
      epilepticus. Place cells fire action potentials when the animal is in a specific
      location in space, the so-called place field. Place cell function correlates well
      with performance in tasks of visual-spatial memory and appears to be an excellent
      surrogate measure of spatial memory. RESULTS: Twelve spontaneous seizures were
      recorded. After the seizures, a marked decrease in firing rate of action
      potentials from place cells was noted, whereas interneuron firing was unchanged.
      In addition, when place cell firing fields persisted or returned, they had
      aberrant firing fields with reduced coherence and information content. In
      addition to postictal suppression of firing patterns, seizures led to the
      emergence of firing fields in previously silent cells, demonstrating a postictal
      remapping of the hippocampus. CONCLUSIONS: These findings demonstrate that
      postictal alterations in behavior are not due solely to reduced neuronal firing.
      Rather, the postictal period is characterized by robust and dynamic changes in
      cell-firing patterns resulting in remapping of the hippocampal map.

PMID- 17437415
TI  - Historical perspective on PTZ-induced seizures.

PMID- 17437417
TI  - Translational mini-review series on vaccines: Peptide vaccines for myeloid
      leukaemias.
AB  - The graft-versus-leukaemia (GVL) effect following allogeneic stem cell
      transplantation is clear evidence that T lymphocytes can control and eliminate
      myeloid leukaemias. The successful identification of a range of leukaemia
      specific antigens (LSA) in recent years has stimulated efforts to induce
      leukaemia specific T cell responses to these antigens with peptide vaccines. An
      ideal LSA should be restricted in its expression to leukaemia including
      progenitor cells, intrinsically connected with the leukaemic phenotype, and
      capable of inducing strong cytotoxic T cell responses to the leukaemia. Peptides
      from three well-characterized LSA, the breakpoint cluster region-abelson (BCR
      ABL) fusion protein of chronic myelogenous leukaemia, proteinase-3 and Wilms
      tumour 1 protein, serve as the basis for several clinical trials using peptide
      and adjuvants to treat patients with a variety of myeloid malignancies.
      Preliminary results from these studies indicate that these peptides induce immune
      responses which can translate into clinical responses which include complete
      remissions from leukaemia. These promising early results point the way to
      optimizing the administration of peptide vaccines and suggest ways of combining
      vaccination with allogeneic stem cell transplantation to boost GVL effects.

PMID- 17437418
TI  - Translational mini-review series on vaccines: Monitoring of human papillomavirus
      vaccination.
AB  - Persistent infection with oncogenic human papillomavirus (HPV) is a necessary
      cause of cervical cancer. Moreover, HPV type 16 (and to a lesser degree HPV type
      18) is linked with more rare cancers, namely cancer of the vulva, vagina, penis,
      anus, oropharynx and larynx. Effective prophylactic vaccines have been developed.
      In this review, we briefly address immunological aspects of HPV infection and the
      results of HPV vaccination trials. Internationally standardized monitoring and
      evaluation of prophylactic HPV vaccination programmes will be essential for
      arriving at the most (cost-)effective strategies for cancer control.

PMID- 17437420
TI  - Increased serum high mobility group box-1 level in Churg-Strauss syndrome.
AB  - Churg-Strauss syndrome (CSS) is a rare form of systemic vasculitis occurring in
      patients with asthma and hypereosinophilia; however, its mechanisms involved in
      the severe tissue inflammation with vasculitis are poorly understood. High
      mobility group box 1 (HMGB1) protein, originally identified as a DNA binding
      protein, also has potent pro-inflammatory and proangiogenic properties. In this
      study, we hypothesized that HMGB1 might be associated with CSS, and examined
      serum HMGB1 levels and compared those of asthma patients and healthy volunteers.
      We also investigated HMGB1 expression in the lesion, and eosinophil HMGB1 amount
      in CSS patients. We found that the serum HMGB1 levels in CSS patients were
      significantly higher than those of asthma patients and healthy volunteers.
      Eosinophils in the CSS lesion expressed HMGB1 and HMGB1 level in eosinophils from
      CSS patients was significantly higher than that of asthma patients, while there
      was no significant difference in HMGB1 levels in peripheral mononuclear cells.
      The serum HMGB1 level in CSS patients decreased after the steroid therapy, and
      showed significant positive correlations with several molecules, including
      soluble interleukin-2 receptor, soluble thrombomodulin, and eosinophil cationic
      protein in sera. We propose that HMGB1 might contribute to the pathogenesis of
      CSS.

PMID- 17437419
TI  - The chemokine network. I. How the genomic organization of chemokines contains
      clues for deciphering their functional complexity.
AB  - Chemokines are a superfamily of small structurally related cytokines that have
      evolved to form a complex network of proteins that typically regulate leucocyte
      traffic but also carry very diverse sets of immune and non-immune functions. Two
      general features of cytokines, redundancy and promiscuity, are particularly
      prominent in chemokines. In part, these properties result from repeated processes
      of gene duplication and diversification, which has led to the present complex
      genomic map of chemokines, which contains cases of non-allelic isoforms, copy
      number polymorphisms and classical allelic variation. This genomic complexity is
      compounded with pre-translational and post-translational mechanisms resulting in
      a complex network of proteins whose essential functions are maintained,
      constituting a remarkable case of robustness reminiscent of crucial metabolic
      pathways. This reflects the adaptation of a system under strong evolutive
      pressure, supporting the concept that the chemokine system is essential for the
      coordination, regulation and fine-tuning of the type of immune response. In this
      first review, we analyse currently available data on the chemokine superfamily,
      focusing on its complex genomic organization. Genes encoding essential
      inflammatory chemokines are grouped into defined chromosomal locations as
      clusters and miniclusters that, from the genetic point of view, can be considered
      single entities given their overall functions (many ligands of a cluster bind to
      a few shared receptors). We will try to interpret this genomic organization of
      chemokines in relation to the main functions acquired by each individual member
      or by each cluster. In a second review, we shall focus on the relationship of
      chemokine variability and disease susceptibility.

PMID- 17437421
TI  - Time-course of Toll-like receptor 2 expression, as a predictor of recurrence in
      patients with bacterial infectious diseases.
AB  - The clinical course of bacterial infectious diseases is often variable,
      especially in elderly patients. Thus, new biological markers have been sought to
      predict the disease outcome. Recent studies have revealed that Toll-like receptor
      (TLR) 2 and/or TLR4 on circulating monocytes are significantly up-regulated in
      bacterial infections. However, the lack of reliable quantification methods
      hampers extensive study on the modulation of these molecules in response to the
      patient's clinical condition. In this study, we developed a new quantitative flow
      cytometric analysis system for TLR2. We then carried out a longitudinal study on
      TLR2 expression levels on monocytes from patients suffering from bacterial
      infectious diseases during and after antibiotic treatment. The clinical outcome
      divided 37 patients into 'cure' (n = 24) and 'recurrence' (n = 13) groups. A
      significant difference between the two groups was recognized in the TLR2 levels
      just after antibiotic treatment (antibody-binding sites/cell, 4395 +/- 784 versus
      5794 +/- 1484, P < 0.001). The risk of recurrence was associated significantly
      with TLR2 (P < 0.001), but not C-reactive protein (P = 0.351) levels assayed
      during the first remission. Furthermore, antibiotic effectiveness was associated
      inversely with TLR2 levels during antibiotic administration (P < 0.001). Taken
      together, TLR2 expression levels on monocytes provide critical information for
      planning treatment against bacterial infectious diseases.

PMID- 17437422
TI  - Lymphocyte-hepatic stellate cell proximity suggests a direct interaction.
AB  - Recent functional research studies suggest an anti-fibrotic role for natural
      killer (NK) cells coupled with a profibrotic role for CD8 cells. However, the
      morphological cellular interplay between the different cell types is less clear.
      To investigate lymphocyte/hepatic stellate cell (HSC) interactions, hepatic
      fibrosis was induced by administering carbon tetrachloride (CCl4)
      intraperitoneally (i.p.) for 4 weeks in C57Bl/6 mice. Animals were killed at 0,
      1, 2, 3 and 4 weeks. Liver sections were stained for Sirius red. Confocal
      microscopy was used to evaluate alpha smooth-muscle actin (alphaSMA) and
      lymphocyte subsets in liver sections. At weeks 0 and 4, liver protein extracts
      were assessed for alphaSMA by Western blotting and isolated liver lymphocytes as
      well as HSC were analysed by fluorescence activated cell sorter (FACS). Similar
      to the results obtained from classical Sirius red staining and alphaSMA blotting,
      analysis of liver sections by confocal microscopy revealed a marked and
      continuous accumulation of alphaSMA staining along sequential experimental check
      points after administering CCl4. Although the number of all liver lymphocyte
      subsets increased following fibrosis induction, FACS analysis revealed an
      increase in the distribution of liver CD8 subsets and a decrease of CD4 T cells.
      Confocal microscopy showed a significant early appearance of CD8 and NK cells,
      and to a lesser extent CD4 T cells, appearing only from week 2. Lymphocytes were
      seen in proximity only to HSC, mainly in the periportal area and along fibrotic
      septa, suggesting a direct interaction. Notably, lymphocyte subsets were
      undetectable in naive liver sections. Freshly isolated HCS show high expression
      of major histocompatibility complex (MHC) class II and CD11c. In the animal model
      of hepatic fibrosis, lymphocytes infiltrate into the liver parenchyma and it is
      thought that they attach directly to activated HSC. Because HSCs express
      CD11c/class II molecules, interactions involving them might reflect that HSCs
      have an antigen-presenting capacity.

PMID- 17437423
TI  - Therapeutic effect of a new immunosuppressive agent, everolimus, on interleukin
      10 gene-deficient mice with colitis.
AB  - A limited number of therapeutic strategies are currently available for patients
      with inflammatory bowel disease (IBD). In particular, the maintenance therapy
      after remission in Crohn's disease (CD) is not satisfactory and new approaches
      are needed. Interleukin-10 gene-deficient (IL-10-/-) mice, a well-characterized
      experimental model of CD, develop severe chronic colitis due to an aberrant Th1
      immune response. Everolimus, an inhibitor of the mammalian target of rapamycin
      (mTOR), a new immunosuppressive reagent, has been used successfully in animal
      models for heart, liver, lung and kidney transplantation. In the present study,
      we examined the efficacy of everolimus in the treatment of chronic colitis in an
      IL-10-/- mouse model. Everolimus was administered orally for a period of 4 weeks
      to IL-10-/- mice with clinical signs of colitis. The gross and histological
      appearances of the colon and the numbers, phenotype and cytokine production of
      lymphocytes were compared with these characteristics in a control group. The 4
      week administration of everolimus resulted in a significant decrease in the
      severity of colitis, together with a significant reduction in the number of CD4+
      T cells in the colonic lamina propria as well as IFN-gamma production in colonic
      lymphocytes. Everolimus treatment of established colitis in IL-10-/- mice
      ameliorated the colitis, probably as a result of decreasing the number of CD4+ T
      cells in the colonic mucosa and an associated reduction in IFN-gamma production.

PMID- 17437424
TI  - Inhalation of glutamic acid decarboxylase 65-derived peptides can protect against
      recurrent autoimmune but not alloimmune responses in the non-obese diabetic
      mouse.
AB  - Systemic administration of islet-derived antigens has been shown to protect
      against diabetes in the non-obese diabetic (NOD) mouse by the induction of
      antigen-specific regulatory T cells. Bystander regulation to related and
      unrelated islet-derived antigens (intramolecular and intermolecular recognition)
      in this context is recognized. We tested if intranasal administration of glutamic
      acid decarboxylase 65 (GAD 65)-derived peptides could protect against both
      autoimmune and, through bystander regulation, alloimmune responses in a NOD mouse
      model. Spontaneously diabetic female NOD mice underwent islet transplantation
      from either C57Bl/6 or NOD islet donors. Islet recipients were treated with
      intranasal GAD 65-derived peptides or control (ovalbumin) peptide pre- and post
      transplantation. In-vitro analysis of the effect of inhalation was defined using
      lymph node proliferation assays and supernatant analysis for cytokines. GAD 65
      derived peptide inhalation resulted in significant protection against recurrent
      autoimmune disease, with the generation of an interleukin (IL)-10-producing
      immune phenotype in a syngeneic islet transplant model. This phenotype, however,
      was not robust enough to protect against alloimmune responses. Inhalation of GAD
      derived peptides induces an immunoregulatory response that protects against
      recurrent autoimmune, but not alloimmune responses in the NOD mouse.

PMID- 17437425
TI  - In vivo treatment with the herbal phenylethanoid acteoside ameliorates intestinal
      inflammation in dextran sulphate sodium-induced colitis.
AB  - Recently we demonstrated that in inflammatory bowel disease (IBD) macrophage
      oxidative burst activity is increased and NADPH oxidase mRNA is induced. The
      herbal phenylethanoid acteoside isolated from Plantago lanceolata L. was shown to
      exhibit anti-oxidative potential. Using the dextran sulphate sodium (DSS)-induced
      colitis model, in this study we have assessed whether systemic application of
      acteoside affects colitis. Colitis was induced by DSS in Balb/c mice. Treatment
      with acteoside (120, 600 microg/mouse/day) was performed intraperitoneally. The
      colon lengths were determined. Colonic tissue was scored histologically (max.
      score 8) by a blinded investigator. T cells isolated from mesenteric lymph nodes
      (MLN) were stimulated with anti-CD3 antibody in the presence of interleukin (IL)
      2 (final concentration 10 U/ml). After incubation for 24 h, IL-1beta, IL-6, IL-12
      tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma levels in
      supernatants were analysed by the beadlyte cytokine detection system.
      Histological scoring of colonic tissue revealed that application of acteoside was
      followed by a significantly improved histological score. In acute colitis the
      histological score was 3.2 with acteoside versus 5.2 with phosphate-buffered
      saline (PBS) (P < 0.02). In chronic colitis both 120 microg (3.3 versus 5.2) or
      600 microg acteoside (3.0 versus 5.2) significantly ameliorated colitis (both P <
      0.02). Stimulated MLN from mice with chronic DSS-induced colitis treated with
      acteoside showed a significant down-regulation of IFN-gamma secretion (195 pg/ml
      with 600 microg acteoside versus 612 pg/ml with PBS, P < 0.02). Inhibition of
      oxidative burst activity with acteoside reduced mucosal tissue damage in DSS
      colitis and could be a therapeutic alternative for IBD treatment. Further studies
      of this agent are warranted.

PMID- 17437426
TI  - What is the role of inflammation in the pathogenesis of prostate cancer?

PMID- 17437427
TI  - Aspirin use and transrectal ultrasonography-guided prostate biopsy: a national
      survey.

PMID- 17437428
TI  - The modern management of upper urinary tract urothelial cancer: tumour diagnosis,
      grading and staging.

PMID- 17437429
TI  - The modern management of upper tract urothelial cancer: surgical treatment.

PMID- 17437430
TI  - Upper urinary tract transitional cell carcinoma: current treatment overview of
      minimally invasive approaches.

PMID- 17437431
TI  - Testicular tumours in children: a single-institutional experience.
AB  - OBJECTIVE: To report our experience of testicular and paratesticular tumours in
      children, as such tumours are rare, and historically yolk sac tumour has been
      described as the most common lesion in children, but recent reports suggest that
      benign testicular lesions might be more common. PATIENTS AND METHODS: We reviewed
      retrospectively the records of children treated for testicular tumours from 1998
      to 2005. The patients' age, clinical presentation, diagnostic procedures,
      treatment methods, histopathological findings, and outcome were recorded.
      Patients aged>144 months and those with non-primary metastatic lesions were
      excluded. RESULTS: In all, 11 patients met our criteria, with a mean age of 37
      months (range 9 days to 144 months). Pathological analysis revealed teratoma in
      four patients, yolk sac tumour in two, epidermoid cysts in two, extrarenal
      nephroblastomatosis in one, and paratesticular rhabdomyosarcomas in two. The most
      common clinical presentation was a painless testicular mass. Depending on the
      clinical presentation and pathology, scrotal ultrasonography, tumour markers
      (alpha-fetoprotein and beta-human chorionic gonadotrophin), and/or staging
      computed tomography (CT) were obtained in eight patients. All patients had a
      radical orchidectomy. Three patients had elevated tumour markers that normalized
      after orchidectomy. CT revealed extensive mediastinal adenopathy in one patient
      with rhabdomyosarcoma. Chemotherapy was administered to both patients with
      rhabdomyosarcoma. CONCLUSION: Although there were few patients, most of the
      lesions were benign tumours, with the most common histological subtype being
      teratoma. As both malignant and paratesticular lesions occurred at a significant
      frequency, we would continue to advocate an initial radical inguinal approach at
      which time testis-sparing could be considered if the preoperative evaluation was
      favourable, and frozen-section analysis at the time of surgery confirms a benign
      lesion.

PMID- 17437432
TI  - Clinical outcome following post-chemotherapy retroperitoneal lymph node
      dissection in men with intermediate- and poor-risk nonseminomatous germ cell
      tumour.
AB  - OBJECTIVE: To evaluate the outcome in patients treated with chemotherapy and
      retroperitoneal lymph node dissection (RPLND) after an initial diagnosis of
      International Germ Cell Cancer Collaborative Group (IGCCCG) intermediate- and
      poor-risk metastatic nonseminomatous testicular germ cell tumour (NSGCT), as the
      integration of chemotherapy and surgery in managing advanced NSGCT continues to
      develop. PATIENTS AND METHODS: Between 1989 and 2003, 157 patients initially
      diagnosed with IGCCCG intermediate- and poor-risk NSGCT had RPLND after
      chemotherapy at the authors' institution, with a median follow-up of 36 months.
      Progression-free probability (PFP) and disease-specific survival (DSS) were
      estimated using the Kaplan-Meier method. Cox proportional hazards regression
      analysis was used to assess the prognostic significance of risk factors for
      disease progression after RPLND. RESULTS: In all, 68 (43%) and 89 (57%) patients
      were assigned as intermediate- and poor-risk, respectively. At the time of RPLND
      the median residual retroperitoneal mass was 3.0 cm and 29 (19%) men had elevated
      serum tumour markers (alpha-fetoprotein, human chorionic gonadotrophin, or both).
      Retroperitoneal residual masses were completely resected in 147 (94%) patients;
      retroperitoneal histology revealed fibrosis in 73 (47%), teratoma in 63 (40%) and
      viable GCT in 21 (13%). The 5-year overall DSS and PFP were 81% and 70%,
      respectively. Patients with poor-risk NSGCT were at no greater risk of disease
      progression than those with intermediate-risk NSGCT. In a multivariate analysis,
      residual mass size, incomplete surgical resection and the presence of teratoma
      and viable germ cell cancer independently predicted disease progression after
      RPLND. CONCLUSIONS: Patients with advanced NSGCT have long-term freedom from
      disease progression when chemotherapy is combined with resection of residual
      masses. Our data suggest that the tumour response to chemotherapy, coupled with
      complete resection of all residual masses, predicts long-term freedom from
      disease progression.

PMID- 17437433
TI  - 'Skipping' is still a problem with radiofrequency ablation of small renal
      tumours.
AB  - OBJECTIVE: To evaluate the homogeneity and extent of necrosis obtained with next
      generation radiofrequency ablation (RFA) equipment and techniques, as incomplete
      tumour necrosis, or 'skipping', has been documented after RFA of renal tumours
      and subsequent partial nephrectomy, but this was assumed to result from
      insufficient energy deposition with first-generation low-energy generators.
      PATIENTS AND METHODS: In all, 17 patients with solitary renal tumours of <or=4 cm
      were treated with RFA under laparoscopic control. A state-of-the-art monopolar
      RFA generator and 15 G multi-tined needle probes were used. The probe tines were
      deployed to create an ablation zone>0.5-1.0 cm beyond the sonographically
      controlled tumour borders. Target temperatures of 105 degrees C were applied in
      three cycles for 10-30 min at up to 150 W. Tumours were then removed by
      laparoscopic partial nephrectomy and specimens evaluated by detailed histology.
      RESULTS: The mean (range) resected tumour size was 22 (11-40) mm, the mean RFA
      time was 39 (27-59) min and the mean surgical resection time was 25 (12-45) min.
      In 13 patients, haemostasis was sufficient to avoid the renal pedicle being
      clamped. Intraoperative repeated positive margins in one patient required a
      laparoscopic radical nephrectomy. Thirteen (76%) renal masses showed
      histologically complete ablation of the entire tumour. Of the four RFA failures,
      three tumours were >3 cm in diameter, two were highly vascularized and three had
      a very heterogeneous tissue texture. CONCLUSION: Even with state-of-the-art
      technology, skipping remains a problem with RFA for small renal masses and
      renders the technique unreliable.

PMID- 17437434
TI  - Renal tumour size measured radiologically before surgery is an unreliable
      variable for predicting histopathological features: benign tumours are not
      necessarily small.
AB  - OBJECTIVE: To compare histopathological findings as a function of radiological
      tumour size, as published data suggest that small renal tumours are often benign
      and large tumours are renal cell cancer (RCC). PATIENTS AND METHODS: Data from
      543 surgically treated patients with solid renal tumours were analysed
      retrospectively. Tumour size measured by computed tomography (CT) before surgery
      was stratified into seven subgroups (cm): 0-2, 2.1-3, 3.1-4, 4.1-5, 5.1-6, 6.1-7
      and >7, and correlated with final histology. RESULTS: In all, 80 lesions (14.7%)
      were benign on final histology; tumour size did not correlate with benign
      histology (P=0.660). Histopathological tumour size was not statistically
      significant different (P=0.521) from measured tumour size on CT, and there was no
      statistical significance between CT and histopathological tumour size (P=0.528).
      Only 13 (17%) of lesions were correctly defined as benign on CT before surgery,
      whereas 67 (83%) were considered to be suspicious for malignant disease. Only one
      patient with a tumour correctly defined as benign had a radical nephrectomy; by
      contrast, 28 of 67 (42%) had a radical nephrectomy for benign lesions not
      correctly identified as benign on CT before surgery (P<0.001). CONCLUSION:
      Substantially many renal masses are benign, independent of tumour size. Radical
      nephrectomy could potentially have been avoided in 42% of patients with benign
      renal tumours. These data provide a good argument for the use of a more refined
      preoperative diagnostic evaluation, in particular needle biopsy.

PMID- 17437435
TI  - Prognostic accuracy of an artificial neural network in patients undergoing
      radical cystectomy for bladder cancer: a comparison with logistic regression
      analysis.
AB  - OBJECTIVE: To compare the prognostic performance of an artificial neural network
      (ANN) with that of standard logistic regression (LR), in patients undergoing
      radical cystectomy for bladder cancer. PATIENTS AND METHODS: From February 1982
      to February 1994, 369 evaluable patients with non-metastatic bladder cancer had
      pelvic lymph node dissection and radical cystectomy for either stage Ta-T1 (any
      grade) tumour not responding to intravesical therapy, with or with no carcinoma
      in situ, or stage T2-T4 tumour. LR analysis based on 12 variables was used to
      identify predictors of overall 5-year survival, and the ANN model was developed
      to predict the same outcome. The LR analysis, based on statistically significant
      predictors, and the ANN model were the compared for their accuracy in predicting
      survival. RESULTS: The median age of the patients was 63 years, and overall 201
      of them died. The tumour stage and nodal involvement (both P<0.001) were the only
      statistically independent predictors of overall 5-year survival on LR analysis.
      Based on these variables, LR had a sensitivity and specificity for predicting
      survival of 68.4% and 82.8%, respectively; corresponding values for the ANN were
      62.7% and 86.1%. For LR and ANN, the positive predictive values were 78.6% and
      76.2%, and the negative predictive values were 73.9% and 76.5%, respectively. The
      index of diagnostic accuracy was 75.9% for LR and 76.4% for ANN. CONCLUSIONS: The
      ANN accurately predicted the survival of patients undergoing radical cystectomy
      for bladder cancer and had a prognostic performance comparable with that of LR.
      As ANNs are based on easy-to-use software that can identify nonlinear
      interactions between variables, they might become the preferred tool for
      predicting outcome.

PMID- 17437436
TI  - Immunohistochemical markers in urinary bladder carcinomas from paraffin-embedded
      archival tissue after storage for 5-70 years.
AB  - OBJECTIVE: To evaluate archival tissue specimens from bladder tumours and seek
      molecular changes in samples collected over seven decades previously, as although
      the frequencies of some cancer types have remained stable during the last 50
      years, the incidence of others, including bladder tumours, has increased
      significantly, and molecular analyses of bladder cancer over periods with an
      increasing incidence are of interest as the findings might reflect varying
      external influences. MATERIALS AND METHODS: Immunohistochemical staining with the
      biological markers p53 protein, p16 protein, epidermal growth factor receptor
      (EGFR), cytokeratin 7 and high molecular weight 34betaE12 cytokeratin (HMW
      cytokeratin, characteristic of basal cells) was used on archival, paraffin wax
      embedded autopsy/biopsy tissue material collected from 144 patients with invasive
      bladder cancer (World Health Organisation grade II and III). The cases were
      selected from the periods 1932-48, 1950-59, 1960-70 and 1990-2004. Control
      immunohistochemistry was done on available normal tissue (i.e. connective and
      fatty tissue, heart, lungs and normal urinary bladder epithelium) obtained from
      the autopsies. RESULTS: The normal tissues were all largely negative for EGFR,
      had <1% positively stained nuclei for p53 and strong positive reactions for p16,
      and in epithelial tissues the two cytokeratins were detected. The positive scores
      for HMW-cytokeratin in the tumour tissue decreased significantly from
      approximately 90% to 30% over the 70 years. For p53 there was a higher fraction
      of positive scores (borderline significant) with time. The p16-positive tumours
      showed no significant variation, with the highest frequency of positive scores in
      recent years. Overexpression of EGFR in the tumours was significantly correlated
      with the occurrence of HMW-cytokeratin and decreased from approximately 85% to
      65% (not significant), with the lowest frequency in the samples from 1990 to
      2004. Autolysis after death or long storage periods did not compromise good
      quality in the histochemical analyses of the autopsy tissue. CONCLUSION: The
      higher frequency of HMW-cytokeratin, lower p53 accumulation and more EGFR
      expression in grade II and III urinary bladder carcinomas from the 1930s could
      indicate different phenotypes in bladder cancer during this 70-year period. The
      successful detection of these protein markers in old archival material allows
      larger retrospective studies that might increase the understanding of molecular
      carcinogenesis in bladder cancer.

PMID- 17437437
TI  - Reliability of preoperative diagnostics and location of lymph node metastases in
      presumed unilateral prostate cancer.
AB  - OBJECTIVE: To investigate the reliability of preoperative diagnostics in
      predicting the true histopathological stage and grade of prostate cancer, and to
      examine whether lymph node (LN) metastases in unilateral prostate cancer are
      located unilaterally and therefore whether it is justified to dissect only the
      ipsilateral LNs in presumed unilateral disease. PATIENTS AND METHODS: LN
      metastases in clinically localized prostate cancer are often located near the
      internal iliac vessels. They will be detected by extended or sentinel pelvic LN
      dissection (PLND). Both techniques might be time-consuming and require extensive
      surgical experience. In all, 564 men with impalpable or unilateral palpable
      prostate cancer and positive biopsy cores only in one prostate lobe had a radical
      prostatectomy (RP) combined with radio-guided PLND and in some cases an extended
      PLND. RESULTS: A median of six sentinel LNs (mean, seven) and six non-sentinel
      LNs (mean, seven) were dissected per patient; 52 of 564 men (9.2%) had positive
      LNs. Most men with unilateral disease had LN metastases on the same side of the
      pelvis. Comparing the clinical stage and grade with the tumour stage and grade of
      the RP specimen, there was a high percentage of upstaging and upgrading even in
      men with only one positive biopsy core. CONCLUSION: Unilateral prostate cancer
      preferentially metastasizes to the ipsilateral pelvic LNs. Because there are a
      few cases of bilateral LN metastases even in unilateral disease, and as it is not
      possible to reliably predict unilateral disease on the basis of biopsy features,
      PLND only on the tumour-bearing side has a high risk of understaging, and would
      possibly leave LN metastases behind.

PMID- 17437438
TI  - Magnetic resonance imaging-directed transrectal ultrasonography-guided biopsies
      in patients at risk of prostate cancer.
AB  - OBJECTIVE: To evaluate whether using endorectal-coil magnetic resonance imaging
      (erMRI) before transrectal ultrasonography (TRUS)-guided biopsies of the prostate
      increases the yield of cancer in a high-risk population, and in a subset analysis
      to compare the yield with high-field (3 T) vs lower field (1.5 T) MRI. PATIENTS
      AND METHODS: Between March 2003 and November 2005, 26 consecutive patients had
      erMRI before their TRUS biopsy of the prostate (median age 62 years, range 32
      76). The median prostate-specific antigen (PSA) level was 8.40 (2.1-85.9) ng/mL.
      All patients had at least one previous negative prostate biopsy (median 3, range
      1-12). Twenty-three patients had at least one risk factor for prostate cancer
      (family history, high PSA velocity, low percentage of free PSA, prostatic
      intraepithelial neoplasia or atypical small acinar proliferation on previous
      biopsy). MRI studies consisted of T2-weighted and dynamic contrast-enhanced (DCE)
      imaging studies. RESULTS: There was a close correlation between T2-weighted and
      DCE images (85% agreement, P<0.001). Neither T2-weighted nor DCE imaging
      correlated with a higher yield for cancer on final biopsy (T2, positive
      predictive value, PPV, 20%, negative PV, NPV, 14%, P=0.21; DCE, PPV 21%, NPV 15%,
      P=0.26). Combining the two methods did not improve the cancer yield. There was no
      significant difference in the probability of cancer based on 1.5 T or 3 T imaging
      (17% vs 16%, P=0.88). CONCLUSION: Although erMRI before TRUS-guided biopsies
      tended to give higher cancer yields the difference was not statistically
      significant. Reasons for this might include suboptimal localisation of the MRI
      findings and the biopsy location. Better methods for fusing MRI and TRUS images
      are presently being developed at our institution to allow more accurate
      targeting.

PMID- 17437439
TI  - Pre-clinical and clinical evaluation of estramustine, docetaxel and thalidomide
      combination in androgen-independent prostate cancer.
AB  - OBJECTIVE: To evaluate the combination of docetaxel plus estramustine (which
      prolongs survival in patients with androgen-independent prostate cancer, AIPC),
      and thalidomide (that also adds to docetaxel activity), both pre-clinically and
      clinically in AIPC. PATIENTS, MATERIALS AND METHODS: In the pre-clinical
      evaluation we injected PC3 cells subcutaneously into severely combined
      immunodeficient mice and started treatment after the tumour volume reached 50
      mm3. We also evaluated the combination using luciferase-labelled PC3M-luc-C6
      cells in nude mice. We enrolled 20 patients with metastatic progressive AIPC into
      a phase II clinical trial to evaluate this combination. Docetaxel (30 mg/m2) was
      administered every week, for 3 of 4 weeks. The dose of thalidomide was 200 mg/day
      and estramustine was given three times a day at 1, 2, 3, 8, 9, 10, 15, 16 and 17
      days. RESULTS: In the mice, thalidomide with docetaxel plus estramustine reduced
      tumour volume by 88% at 17 days vs the control treatment (p=0.001). The
      combination of docetaxel, estramustine and thalidomide nearly eradicated the
      signal from the luciferase-expressing PC3M cells in the metastasis model.
      Clinically, the progression-free time was 7.2 months with this combination; 18 of
      20 patients had a decline of half or more in prostate-specific antigen level and
      two of 10 patients with soft-tissue lesions had a partial response on computed
      tomography. There were 24 grade 3 and two grade 4 complications associated with
      this combination. There was a statistically significant association between
      overall survival and the CYP1B1*3 genotype (P=0.013). CONCLUSION: Docetaxel-based
      chemotherapy is now regarded as a standard regimen for metastatic AIPC. The
      combination of estramustine, docetaxel and thalidomide is an advantageous
      treatment in pre-clinical models of prostate cancer and is a safe, tolerable and
      active regimen in patients with AIPC.

PMID- 17437440
TI  - Post-stroke urinary incontinence with impaired awareness of the need to void:
      clinical and urodynamic features.
AB  - OBJECTIVE: To describe a clinical subtype of urinary incontinence (UI) after a
      stroke, i.e. with impaired awareness of the need to void (IA-UI), and to compare
      it to urge UI after a stroke for the risk factors and medium-term outcome.
      PATIENTS AND METHODS: In a consecutive sample of 315 hospitalized stroke patients
      who were clinically stable and able to communicate, 65 with UI were identified
      (27 urge UI, 38 IA-UI). All had a comprehensive clinical assessment and cerebral
      computed tomography (CT). Cysto-urethrometry was performed in seven patients with
      IA-UI. RESULTS: Of the 38 patients with IA-UI, 16 were partially aware of
      leakage, but not of bladder fullness; the remaining 22 denied leakage. Patients
      with IA-UI were more functionally impaired (P=0.001), had more visible new CT
      lesions (24 of 38 vs 10 of 27, P=0.04) and less frontal lobe involvement (seven
      of 24 vs seven of 10, P=0.05) than those with urge UI. Ten of 12 patients with
      parietal lobe involvement denied leakage; no particular lesion pattern was found
      in those with partial awareness. Two patients had normal cysto-urethrometry, four
      showed terminal detrusor overactivity, and one had an incompetent urethral
      closure mechanism. In all, bladder sensation was reduced or absent. Only two of
      the surviving patients had regained continence after 1 year, whereas half of
      those with urge UI had become continent. CONCLUSION: IA-UI after a stroke differs
      from urge UI in clinical and prognostic respects, and probably reflects greater
      brain damage. It might explain the prognostic importance of stroke-related UI.
      There are various urodynamic patterns. Patients with better preserved insight
      might benefit from early awareness training and even from additional medical
      treatment if bladder overactivity is present; this needs further investigation.

PMID- 17437441
TI  - Robotic radical prostatectomy: outcomes of 500 cases.
AB  - OBJECTIVE: To report the outcomes of 500 robotically assisted laparoscopic
      radical prostatectomies (RALPs), a minimally invasive alternative for treating
      prostate cancer. PATIENTS AND METHODS: In all, 500 patients had RALP over a 30
      month period. A transperitoneal six-port approach was used in each case, with the
      da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA, USA).
      Prospective data collection included quality-of-life questionnaires, basic
      demographics (height, weight and body mass index), prostate specific antigen
      (PSA) levels, clinical stage and Gleason grade. Variables assessed during RALP
      were operative duration, estimated blood loss (EBL) and complications, and after
      RALP were hospital stay, catheter time, pathology, PSA level, return of
      continence and potency. RESULTS: The mean (range) duration of RALP was 130 (51
      330) min; all procedures were successful, with no intraoperative transfusions or
      deaths. The mean EBL was 10-300 mL; 97% of patients were discharged home on the
      first day after RALP with a mean haematocrit of 36%. The mean duration of
      catheterization was 6.9 (5-21) days. The positive margin rate was 9.4% for all
      patients; i.e. 2.5% for T2 tumours, 23% for T3a and 53% for T4. The overall
      biochemical recurrence free (PSA level<0.1 ng/mL) survival was 95% at mean follow
      up of 9.7 months. There was complete continence at 3 and 6 months in 89% and 95%
      of patients, respectively. At 1 year 78% of patients were potent (with or without
      the use of oral medications), 15% were not yet able to sustain erections capable
      of intercourse, and another 7% still required injection therapy. CONCLUSION: RALP
      is a safe, feasible and minimally invasive alternative for treating prostate
      cancer. Our initial experience with the procedure shows promising short-term
      outcomes.

PMID- 17437442
TI  - Robotically assisted laparoscopic pyeloplasty: a transatlantic comparison of
      techniques and outcomes.
AB  - OBJECTIVE: To report a comparison of two techniques of robotically assisted
      laparoscopic dismembered pyeloplasty (RALDP), and their associated outcomes, for
      treating pelvi-ureteric junction obstruction (PUJO), evaluating the potential
      differences in the initial 50 cases of two centres in North America and Europe.
      PATIENTS AND METHODS: Between November 2001 and August 2005, 100 patients had
      transperitoneal RALDP for PUJO in one centre in the USA (group 1) and one in
      France (group 2). Group 1 consisted of 50 patients (30 males and 20 females, mean
      age 31 years, range 16-62) and group 2 of 50 patients (17 males and 32 females,
      one bilateral PUJO; mean age 39 years, range 17-81). The right side was affected
      in 30 (60%) patients in group 1 and 32 (64%) in group 2. Differences in
      preoperative evaluation, surgical technique and follow-up were evaluated.
      RESULTS: In group 1 all procedures were completed laparoscopically. One
      conversion was necessary in group 2 due to technical difficulties. The mean
      operative duration was 122 min (group 1) and 127 min (group 2); the estimated
      blood loss was negligible (<100 mL) in both groups. Surgical findings included 15
      patients with crossing vessels in group 1 and 28 in group 2. There were no peri
      operative complications in either group. The mean hospital stay was 1.1 days in
      group 1 and 5.8 days in group 2, reflecting differences in practice patterns. All
      patients were asymptomatic at stent removal and in subsequent clinical
      evaluations in both groups. CONCLUSION: The combination of results form both
      series provide information suggesting that the robotically assisted approach is a
      viable treatment option. The results reflect some differences in techniques,
      follow-up and practice patterns, but the outcomes were equally effective on both
      continents. Further follow-up will allow us to determine the long-term efficacy.

PMID- 17437443
TI  - Differential expression of facilitative glucose transporters in normal and tumour
      kidney tissues.
AB  - OBJECTIVE: To investigate the differences in the pattern of glucose transporter
      (GLUT) gene expression between normal and tumour tissues and among histological
      subtypes of renal cell carcinomas (RCCs), as malignant cells are characterized by
      increased glucose uptake and use. MATERIALS AND METHODS: Enhanced glucose uptake
      probably depends on the overexpression of GLUT, usually GLUT1 and/or GLUT3, but
      there are few comprehensive studies to evaluate the relative expression pattern
      and level of GLUT in normal and tumour kidney tissues, especially of the recently
      identified GLUT genes. In all, 71 kidney surgical samples were evaluated using
      reverse transcriptase-polymerase chain reaction (RT-PCR) for GLUT1-14 in normal
      and tumour (clear cell, papillary and chromophobe RCC, and oncocytoma) tissues.
      The expression levels for GLUT1-5, 9, 10 and 12 were quantified by real-time
      quantitative PCR. RESULTS: The RT-PCR results showed that normal kidney tissue
      expresses all the GLUT isoforms. In clear cell RCC GLUT1 expression increased
      (P<0.001) while GLUT4, 9 and 12 decreased (P<0.001). In papillary RCC there were
      no significant increases in GLUT expression, with only GLUT12 significantly
      expressed at lower levels (P<0.001). In chromophobe RCC the expression of GLUT4
      increased (P<0.05), and GLUT2 and 5 decreased (P<0.01), whereas in oncocytoma
      tissue there were no significant changes in the expression of GLUT1 (P<0.01), 2,
      5, 9 (P<0.001) and 10 (P<0.05). CONCLUSIONS: These results suggest that high
      affinity GLUTs might have a major role in enhanced glucose uptake in kidney
      tumours, and that histopathological types are characterized by specific patterns
      of GLUT expression.

PMID- 17437444
TI  - The expression of vascular endothelial growth factor is associated with the risk
      of cancer progression after radical prostatectomy.
AB  - OBJECTIVE: To analyse the prognostic value of vascular endothelial growth factor
      (VEGF) in men with clinically localized prostate cancer. PATIENTS AND METHODS:
      Paraffin wax-embedded sections from the radical prostatectomy (RP) specimens of
      40 men operated for clinically localized prostate cancer were used to build
      tissue microarrays. Of these patients, 17 had cancer progression and bone
      metastases after RP (group 1), and 23 remained free-of-tumour recurrence after RP
      (group 2). VEGF-A expression was examined in the RP specimens using
      immunohistochemistry. RESULTS: The groups had similar tumour characteristics in
      terms of prostate-specific antigen level, Gleason score, and pathological stage.
      VEGF-A expression was significantly higher in group 1 than in group 2 (P=0.046).
      In logistic regression analysis, VEGF-A expression was the most significant
      predictive factor of cancer progression after RP. CONCLUSION: VEGF-A expression
      in prostate cancer tissue is associated with the risk of cancer progression after
      RP. These results suggest that VEGF-A expression has a prognostic impact in
      clinically localized prostate cancer.

PMID- 17437446
TI  - And my prostate just keeps growing!

PMID- 17437447
TI  - The effect of male circumcision on sexuality.

PMID- 17437448
TI  - Young men with prostate cancer: are they different and how should they be
      managed?

PMID- 17437449
TI  - Psagraph: a simple graphical and useful tool for follow-up and decision on biopsy
      and treatment of patients with prostatic diseases.

PMID- 17437450
TI  - Clinically significant prostate cancer found incidentally in radical
      prostatectomy specimens.

PMID- 17437452
TI  - The Vattikuti Institute prostatectomy.

PMID- 17437453
TI  - Surgical principles of omentoplasty in urology.

PMID- 17437455
TI  - A family systems-based model of organizational intervention.
AB  - Employee assistance professionals are expected to be proficient at intervening in
      organizations and creating meaningful behavioral change in interpersonal
      functioning. Because of their training in family systems theories and concepts,
      marriage and family therapists (MFTs) are well suited to serve organizations as
      "systems consultants." Unfortunately, the authors were unable to identify any
      family systems-based models for organizational intervention that have been
      empirically tested and supported. In this article, the authors present a family
      systems-based model of intervention that they developed while working in an
      employee assistance program (EAP). They also present research that was used to
      refine the model and to provide initial support for its effectiveness.

PMID- 17437456
TI  - Organizational Systems Questionnaire (OSQ) Validity Study.
AB  - Marriage and family therapists (MFTs), who are trained in systems theory and
      consult with complex and difficult systems (e.g., couples and families), are
      uniquely suited to both assess and intervene in broader organizational systems.
      However, MFTs are in need of more systemically designed assessment tools to guide
      and inform their interventions with organizational systems. This study examined
      the construct and concurrent validity of the Organizational Systems Questionnaire
      (OSQ). The OSQ is designed to use a systemic framework to measure the construct
      of organizational functioning. Participants were simultaneously administered the
      Abridged Job Description Index, Organizational Commitment Questionnaire, Stress
      in General, and Communication Satisfaction Questionnaire scales along with the
      OSQ. The OSQ demonstrated good construct validity, factor analysis indicates it
      is measuring one global factor of organizational functioning, reliability was
      strong (alpha = .91), and it showed high levels of internal consistency. The OSQ
      also demonstrated positive concurrent validity with acceptable levels of
      correlation with the other organizational measures. Overall, the OSQ was found to
      be a useful and psychometrically sound single-factor measure of organizational
      functioning.

PMID- 17437457
TI  - The role of family therapists in veterinary medicine: opportunities for clinical
      services, education, and research.
AB  - Marriage and family therapists (MFTs) are applying their specific skill set in a
      variety of arenas. A new area for collaboration is veterinary medicine. The
      veterinary medical profession is emphasizing the importance of non-biomedical
      skills such as communication skills, acknowledging that human clientele are
      likely to view their pets as family members, and discussing veterinarian personal
      well-being. Each of these trends has clear application for intervention by MFTs.
      A discussion of how MFTs may be uniquely positioned to assist veterinary medicine
      is presented. An example of collaboration between MFT and veterinary medicine at
      Kansas State University is highlighted. Recommendations are made for development
      of effective educational relationships and possible private sector
      collaborations.

PMID- 17437458
TI  - Attachment-based family therapy: adherence and differentiation.
AB  - This study examined the fidelity of attachment-based family therapy (ABFT) for
      depressed adolescents. Trained observers used the therapist behavior rating scale
      (3rd version) to code therapist behaviors in 45 sessions of ABFT and 45 sessions
      each from two empirically based treatments for adolescent substance abusers:
      multidimensional family therapy (MDFT) and cognitive-behavioral therapy (CBT).
      Results indicate that ABFT therapists employed essential ABFT interventions, such
      as focusing on vulnerable affect, highlighting attachment-related themes, and
      promoting adolescent-parent reattachment through in-session enactments. In
      accordance with the sequential nature of the treatment, these interventions were
      used more extensively during the early stage of treatment, when there is a
      greater focus on reattachment. ABFT was perfectly discriminable from CBT, with
      ABFT therapists using more restructuring and reattachment interventions and CBT
      therapists using more signature CBT interventions, such as cognitive monitoring
      and homework. ABFT was also discriminable from MDFT, with ABFT therapists placing
      a greater emphasis on reattachment. These results suggest that ABFT is a viable
      and differentiated treatment. Together with prior findings supporting its
      efficacy, ABFT should be considered a promising new approach for working with
      depressed adolescents and their families.

PMID- 17437459
TI  - Forgiveness and therapy: a critical review of conceptualizations, practices, and
      values found in the literature.
AB  - This article is a critical review of how forgiveness is conceptualized in the
      family therapy, counseling, and clinical psychology literature. A systematic
      analysis of themes in a fairly comprehensive set of texts was carried out. Three
      main dimensions emerged along which therapist authors' viewpoints can be located:
      essentiality, intentionality, and benevolence. Therapy practices and values that
      correspond with positions along these dimensions are presented. The analysis
      reveals that greater exploration is needed regarding how forgiveness is related
      to diversity (e.g., gender, culture, religion, etc.), marginalization, and
      relations of power. Our objective is to provide a conceptual map for clinicians
      so that they might locate their own thinking about forgiveness and be better
      equipped to work sensitively with the forgiveness views and values of their
      clients.

PMID- 17437460
TI  - Engaging suffering: towards a mindful re-visioning of family therapy practice.
AB  - The myth of problem-free living is easily identifiable in Western culture through
      its childhood fairy tales and modern love stories. Even if inadvertently, the
      field of mental health perpetuates this myth with the very concept of "mental
      health," which implies a state without suffering. Using mindfulness, Buddhists
      assume an alternative stance towards suffering: rather than eliminate it, they
      compassionately engage it. This article explores the potentials of mindfulness as
      an alternative approach to suffering within the context of marriage and family
      therapy. Family therapists can integrate mindfulness principles into their work
      to help clients shift how they relate to the unique forms of suffering that one
      encounters in intimate relationships, such as abuse, divorce, rejection, and
      loss.

PMID- 17437461
TI  - Responding to remediation and gatekeeping challenges in supervision.
AB  - Thirty faculty in randomly selected Commission on Accreditation for Marriage and
      Family Therapy Education (COAMFTE) programs representing four geographical
      regions of the United States were asked to respond to a survey that included
      seven brief vignettes depicting gatekeeping and remediation challenges
      supervisors may face when working with therapists-in-training. Research
      participants were asked to select from among a range of 17 response options and
      were also asked to provide a rationale for the selection of their responses. The
      response rate for the mailed survey was 34%. Telephone interviews were conducted
      with three respondents who had provided especially detailed responses to the open
      ended portions of the mailed survey and who also volunteered to be questioned
      regarding how supervision decisions are made. Results support the conclusion that
      COAMFTE faculty take their gatekeeping function seriously as they balance
      commitments to multiple stakeholders. When presented with hypothetical "bare
      bones" vignettes, the supervisors in our study consistently recommended talking
      with the student in order to more fully understand the context of the student's
      performance problem before deciding how to proceed. Supervisors recommended a
      variety of remediation efforts, but reserved the most severe consequences, such
      as probation, dismissal, and filing an ethics complaint, for the vignette
      involving dishonesty and lack of personal integrity.

PMID- 17437462
TI  - Therapeutic alliance and treatment progress in couple psychotherapy.
AB  - This study examined the ability of the therapeutic alliance to predict treatment
      progress on individual- and relationship-level variables from the early to middle
      phase of couple treatment. Although alliance did not predict progress in
      individual functioning, it accounted for 5-22% of the variance in improvement in
      marital distress. Women's mid-treatment alliance uniquely predicted improvement
      in marital distress, over and above early treatment alliance. When men's
      alliances with the therapist were stronger than their partners' at session 8,
      couples showed more improvement in marital distress. Treatment response was also
      positively associated with women's ratings of their partners' alliance. Results
      confirm that the therapeutic alliance in conjoint treatment is composed of
      distinct client subsystems that are useful predictors of treatment progress.

PMID- 17437463
TI  - Therapists' prototypical assessment of domestic violence situations.
AB  - Prototypical perceptions by therapists have the potential to influence the
      therapeutic process of assessment. The purpose of this study is to begin to
      develop an understanding of how prototypes might affect marriage and family
      therapists' assessments of domestic violence situations. Participants evaluated
      one of three domestic violence scenarios that were identical in dynamics but
      different in terms of sexual orientation of the couple (i.e., heterosexual, gay,
      or lesbian). The most significant finding was that initial assessments of victim
      and perpetrator identification and power attribution differed depending on the
      sexual orientation of the couple. The "man as perpetrator, woman as victim"
      prototypical paradigm for heterosexual domestic violence emerged. In the same-sex
      scenarios, often "both" partners were perceived to be indicated both as victim
      and perpetrator.

PMID- 17437464
TI  - Relationship violence among couples seeking therapy: common couple violence or
      battering?
AB  - Relationship violence is highly prevalent among couples seeking therapy
      (Ehrensaft and Vivian, 1996; Jouriles and O'Leary, 1985), yet few couple
      therapists regularly assess for violence (Dimidjian, Berns, and Jacobson, 1999),
      and there is limited research on the type of violence most characteristic of
      couples in this population. The current study uses latent class analysis to
      examine types of violence in a sample of 273 therapy-seeking couples. The results
      support a three-class typology, with the groups labeled no violence, low-level
      violence, and moderate-to-severe violence. Comparisons between the classes
      support hypothesized differences between groups in degree of marital satisfaction
      and difficulties in communication, providing further validation of the typology
      among couples seeking treatment. Clinical and research implications are
      discussed.

PMID- 17437468
TI  - The revised international health regulations and their relevance to travel
      medicine.
AB  - The revised International Health Regulations 2005 (IHR 2005) will enter into
      force in June 2007. Here we give an overview of the IHR (2005) and their
      relevance to the travel medicine practitioner. The two specific applications of
      the IHR (2005) most likely to be encountered by travelers are the disinsection of
      aircraft to prevent importation of disease vectors and the yellow fever
      vaccination requirements imposed by certain countries. A model of the revised
      international certificate of vaccination or prophylaxis will be shown. The IHR
      (2005) has moved away from the definition of fixed maximum measures relating to
      specific diseases and in their place focus on the issuance of context-specific
      recommendations, made either on a temporary emergency basis or established for
      routine application in respect of ongoing risks of disease spread.

PMID- 17437469
TI  - Knowledge, attitude, and practices with regard to adult pertussis vaccine booster
      in travelers.
AB  - INTRODUCTION: Pertussis is a worldwide, highly communicable, vaccine-preventable
      respiratory disease and is a frequent but often underestimated cause of prolonged
      cough illness in adults. Immunity from childhood pertussis immunization is
      thought to last only up to 10 years. The incidence of adult pertussis has been
      estimated to be 200 to 500 per 100,000 persons-years. Acellular pertussis
      vaccines have been evaluated in adults and confer safe and effective protection
      and now exist as combination vaccine together with tetanus and diphtheria.
      METHODS: We did a questionnaire survey to assess the knowledge, attitude, and
      practices toward pertussis in adult travelers. We consecutively enrolled all
      travelers who presented at the Travellers' Health & Vaccination Centre in
      Singapore in 1 month. RESULTS: Of 218 consecutively enrolled travelers, 184
      (84.4%) completed the questionnaire; of which 80% were Singaporeans. Seventy
      persons (38%) did not know or gave a wrong answer for the mode of transmission of
      pertussis, 147 (83%) had never heard of a pertussis vaccine for adults, and
      almost none had received an adult pertussis vaccine booster. Travelers from
      Western countries were seven times [95% confidence interval (CI): 2-27] more
      likely than Asians to have knowledge about pertussis; women were 4.27 times (95%
      CI: 1.59-11.53) more likely than men to be aware of the booster vaccine, after
      adjusting for nationality ( p= 0.004). CONCLUSIONS: Knowledge about pertussis was
      poor among adult travelers. Although pertussis was viewed as a serious illness by
      the majority of participants, and 38% expressed the desire to be vaccinated,
      almost no one had received the pertussis vaccine booster. Awareness about
      pertussis, its risks, and prevention via vaccination need to be increased among
      adult travelers. Studies are needed to quantify the risk of pertussis in adult
      travelers.

PMID- 17437470
TI  - Sexual behavior, knowledge of STI prevention, and prevalence of serum markers for
      STI among tour guides in Cuzco/Peru.
AB  - BACKGROUND: Sexual behavior during travel has increasingly become a focus of
      travel medicine research. The perceived freedom when away from home can lead to
      increased casual sexual activities, often unprotected. Local sexual partners,
      particularly those who are in close contact with tourists due to their
      occupation, need to be considered more in research. The purpose of this study was
      to explore the sexual behavior, knowledge of STI prevention, and prevalence of
      serum markers of selected STIs in tour guides in Cuzco/Peru. METHODS: In this
      cross-sectional study, 161 tour guides completed a questionnaire consisting of
      information on demographics, sexual behavior, and knowledge about STI prevention.
      Blood samples of the participants were tested for antibodies against HSV2,
      Chlamydia trachomatis, and Treponema pallidum using commercial enzyme-linked
      immunosorbent assay kits. RESULTS: The majority of guides (65%) were sexually
      active during the year prior to the study and 10% had foreign partners.
      Consistent condom use was reported by 38.1%, but almost 42% did not use condoms.
      In total, 27.6% reported symptoms compatible with STI. Three quarters of the
      participants had previously received information on STI prevention, predominantly
      from health professionals. In total, 22% considered themselves at high risk for
      STI. Antibodies against C trachomatis were prevalent in 15%, while 88.2% were
      against HSV2. None had antibodies against T pallidum. CONCLUSIONS: There is an
      inconsistency in reported sexual behavior and reported knowledge about STI
      prevention. Because of the tour guides' bridging position between potential STI
      carriers in tourists and the local population, the reported nonuse of condoms is
      of concern. The prevalence of serum markers supports this concern, which is
      aggravated by the potential of noncurable infections. Current sexual health
      education strategies seem unsatisfactory, and major modifications are highly
      recommended.

PMID- 17437471
TI  - Current perceptions of travelers' diarrhea treatments and vaccines: results from
      a postal questionnaire survey and physician interviews.
AB  - BACKGROUND: Travelers' diarrhea (TD) occurs at high frequency in individuals from
      industrialized countries visiting destinations in nonindustrialized countries and
      may result in chronic complications such as Guillain-Barre syndrome. METHODS: We
      distributed a questionnaire requesting information on physicians' perceptions of
      currently available TD products, hypothesized TD vaccines, and aspects of
      travelers' behavior. Some physicians also were interviewed by telephone. RESULTS:
      We obtained completed questionnaires from named individuals at 68 UK/US clinics.
      These individuals reported seeing a total of approximately 76,500 travelers per
      year, and estimated that 61% (UK) and 77% (US) of travelers present 2 weeks or
      more predeparture. More US (92%) than UK (43%) travelers are advised to purchase
      TD products. In both countries, 85% of travelers would be prescribed an ideal TD
      vaccine, but only approximately 47% (UK) and approximately 65% (US) would
      purchase this vaccine. About 80% of physicians would recommend an hypothesized
      100% effective Campylobacter vaccine for travelers visiting regions where 30% of
      TD cases are caused by Campylobacter. CONCLUSIONS: Physicians support the concept
      of TD vaccines, including campylobacteriosis vaccines. An ideal TD vaccine might
      be purchased by up to 16% (UK) and 28% (US) of relevant travelers. A 100%
      effective Campylobacter vaccine might be purchased by over 2 million UK/US
      travelers per year.

PMID- 17437472
TI  - Are we doing our best to educate travelers about the risks of acute mountain
      sickness? An on-site prospective study in the Himalayas.
AB  - BACKGROUND: Acute mountain sickness (AMS) affects almost half of those ascending
      to heights over 3,000 m. The knowledge and practices concerning AMS have not been
      adequately studied. METHODS: We conducted a prospective on-site study in the
      Himalayas. Between July and October 2004, we approached a convenience sample of
      trekkers during or after their ascent to high altitudes and provided them with
      detailed questionnaires regarding knowledge of and personal experience with AMS.
      RESULTS: One hundred ninety-two travelers (of whom 106 were Israelis and 86
      Western Europeans) participated in the study. One hundred thirty travelers (68%)
      had received any written/oral information about AMS prior to their departure. The
      most common source of information among Israeli travelers was the travel clinic
      (65%), compared to only 9% among Europeans. Overall, 89% were found to have good
      "basic knowledge" about symptoms of AMS (defined as headache plus > or =2 of the
      following: fatigue, dizziness, nausea, insomnia). Travelers who had received
      information about AMS prior to their trip were significantly more knowledgeable
      about symptoms of AMS (p= 0.0001), and treatment options, such as oxygen,
      medications, and rest (p= 0.023, p= 0.024, p= 0.011, respectively). Only 2% of
      the Israelis versus 16% of the Europeans (p= 0.0004) knew that O(2) was a
      treatment option. Forty-seven percent suffered from AMS, which in 50% began at
      3,000 m. About 33 of 90 (37%) of those who suffered AMS symptoms had
      acetazolamide with them, but only 14 actually used it as treatment. CONCLUSIONS:
      Knowledge of AMS among climbers to high altitudes should be fostered, with
      specific emphasis on practical advice.

PMID- 17437473
TI  - Immunogenicity study of abbreviated rabies preexposure vaccination schedules.
AB  - OBJECTIVE: To evaluate abbreviated preexposure rabies vaccination schedules that
      would reduce cost and shorten time required for completion. METHOD: A random
      prospective immunogenicity study, using a group of 96 volunteer preclinical
      veterinary students, primary school children, and hospital-based health care
      workers. They were divided into six groups and administered abbreviated schedules
      of preexposure tissue culture rabies vaccines. Neutralizing antibodies were
      determined on days 0 and 360, and following boosters on days 367 and 374.
      RESULTS: All subjects, including one group that received only 0.1 mL
      intradermally at two sites on one day, had detectable neutralizing antibody
      titers 1 year later and responded with an accelerated antibody response when
      given booster injections. CONCLUSION: It might be possible to develop a 1-week
      and even one clinic visit preexposure vaccine schedule that would provide at
      least 1 year of immune memory.

PMID- 17437474
TI  - Organ transplantations and rabies transmission.

PMID- 17437475
TI  - The risk of acquiring hepatitis A and B among travelers in selected Eastern and
      Southern Europe and non-European Mediterranean countries: review and consensus
      statement on hepatitis A and B vaccination.

PMID- 17437476
TI  - Spontaneous splenic rupture due to Plasmodium vivax in a traveler: case report
      and review.

PMID- 17437477
TI  - Skin features accompanying imported human African trypanosomiasis: hemolymphatic
      Trypanosoma gambiense infection among two French expatriates with dermatologic
      manifestations.

PMID- 17437478
TI  - Genital schistosomiasis in a traveler coming back from Mali.

PMID- 17437479
TI  - Attendances to emergency departments by ill or injured travelers returning from
      abroad.

PMID- 17437481
TI  - Calcineurin inhibitors and rapamycin: cancer protection or promotion?
AB  - Since the introduction of cyclosporin A (CsA) in the early 1980s, the use of
      immunosuppressants has markedly increased. Already established drugs have proved
      effective in the treatment of a wide range of diseases outside transplantation
      medicine and new immunosuppressants have been developed for more specific
      indications such as psoriasis and atopic dermatitis. Patients in transplantation
      medicine as well as in dermatology have benefited significantly from systemic and
      topical application of both new and established drugs. But are these drugs
      without risks? Cancer-protecting effects have been reported for some of the
      available immunosuppressants. Conversely, other publications and the issue of a
      black box warning by the US Food and Drug Administration have increased concerns
      about cancer-promoting effects. Knowledge of the specific effects as well as
      adverse effects is paramount to ensure an application that is safe and beneficial
      for the patient. Here we review the mechanisms of action and therapeutic
      potential, and critically review recent literature with respect to possible
      carcinogenic side effects of systemic and topical CsA, tacrolimus, pimecrolimus
      and rapamycin.

PMID- 17437482
TI  - mTOR as a potential therapeutic target for treatment of keloids and excessive
      scars.
AB  - Keloid is a dermal fibroproliferative disorder characterized by excessive
      deposition of extracellular matrix (ECM) components such as collagen,
      glycoproteins and fibronectin. The mammalian target of rapamycin (mTOR) is a
      serine/theronine kinase which plays an important role in the regulation of
      metabolic processes and translation rates. Published reports have shown mTOR as
      regulator of collagen expression and its inhibition induces a decrease in ECM
      deposition. Our aim was to investigate the role of mTOR in keloid pathogenesis
      and investigate the effect of rapamycin on proliferating cell nuclear antigen
      (PCNA), cyclin D1, collagen, fibronectin and alpha-smooth muscle actin (alpha
      SMA) expression in normal fibroblasts (NF) and keloid fibroblasts (KF). Tissue
      extracts obtained from keloid scar demonstrated elevated expression of mTOR,
      p70KDa S6 kinase (p70S6K) and their activated forms, suggesting an activated
      state in keloid scars. Serum stimulation highlighted the heightened
      responsiveness of KF to mitogens and the importance of mTOR and p70S6K during
      early phase of wound healing. Application of rapamycin to monoculture NF and KF,
      dose- and time-dependently downregulates the expression of cytoplasmic PCNA,
      cyclin D1, fibronectin, collagen and alpha-SMA, demonstrating the anti
      proliferative effect and therapeutic potential of rapamycin in the treatment of
      keloid scars. The inhibitory effect of rapamycin was found to be reversible
      following recovery in the expression of proteins following the removal of
      rapamycin from the culture media. These results demonstrate the important role of
      mTOR in the regulation of cell cycle and the expression of ECM proteins:
      fibronectin, collagen and alpha-SMA.

PMID- 17437483
TI  - Grape seed proanthocyanidins promote apoptosis in human epidermoid carcinoma A431
      cells through alterations in Cdki-Cdk-cyclin cascade, and caspase-3 activation
      via loss of mitochondrial membrane potential.
AB  - Dietary grape seed proanthocyanidins (GSPs) prevent photocarcinogenesis in mice.
      Here, we report that in vitro treatment of human epidermoid carcinoma A431 cells
      with GSPs inhibited cellular proliferation (13-89%) and induced cell death (1
      48%) in a dose (5-100 mug/ml)- and time (24, 48 and 72 h)-dependent manner. GSP
      induced inhibition of cell proliferation was associated with an increase in G1
      phase arrest at 24 h, which was mediated through the inhibition of cyclin
      dependent kinases (Cdk) Cdk2, Cdk4, Cdk6 and cyclins D1, D2 and E and
      simultaneous increase in protein expression of cyclin-dependent kinase inhibitors
      (Cdki), Cip1/p21 and Kip1/p27, and enhanced binding of Cdki-Cdk. The treatment of
      A431 cells with GSPs (20-80 mug/ml) resulted in a dose-dependent increase in
      apoptotic cell death (26-58%), which was associated with an increased protein
      expression of proapoptotic Bax, decreased expression of antiapoptotic Bcl-2 and
      Bcl-xl, loss of mitochondrial membrane potential, and cleavage of caspase-9,
      caspase-3 and PARP. Pretreatment with the pan-caspase inhibitor (z-VAD-fmk)
      blocked the GSP-induced apoptosis in A431 cells suggesting that GSP-induced
      apoptosis is associated primarily with the caspase-3-dependent pathway. Together,
      our study suggests that GSPs possess chemotherapeutic potential against human
      epidermoid carcinoma cells in vitro, further in vivo mechanistic studies are
      required to verify the chemotherapeutic effect of GSPs in skin cancers.

PMID- 17437484
TI  - Detection of perforin and granzyme B mRNA expressing cells in lichen sclerosus.
AB  - Granzyme B and perforin messenger RNA (mRNA) expression has been shown to be a
      specific in vivo activation marker for cytotoxic cells. The aim of this study was
      to assess the contribution of cell-mediated cytotoxicity in the pathogenesis of
      lichen sclerosus. In situ hybridization and immunohistochemistry were performed
      on serial tissue sections of lesional skin biopsies and normal skin as control.
      Immunohistochemical staining showed that the cellular infiltrate of diseased skin
      consisted predominantly of T cells (CD3+) and some B cells (CD20+). Among T cells
      CD4+ and CD8+ cells were found in about equal numbers. In normal skin samples
      perforin and granzyme B mRNA expressing cells were only rarely found. In
      contrast, in biopsies from diseased skin a high percentage of infiltrating cells
      expressed mRNA for perforin and granzyme B. The perforin and granzyme B
      expressing cells were found in the dermal infiltrate and intraepidermally in
      close proximity to keratinocytes suggesting in situ activation of these cells.
      These findings provide evidence that cell-mediated cytotoxicity plays a
      significant role in tissue destruction in lichen sclerosus.

PMID- 17437485
TI  - Plasma concentration of selected neuropeptides in patients suffering from
      psoriasis.
AB  - The aim of this study was to evaluate plasma levels of substance P (SP),
      calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and
      neuropeptide Y (NPY) during psoriasis course. METHODS: Seventy-three patients
      with psoriasis and 32 healthy volunteers were included. Detailed demographic and
      disease anamnesis was obtained from every patient. The disease severity was
      assessed using the Psoriasis Area and Severity Index score. Plasma levels of SP,
      CGRP, VIP and NPY were measured radioimmunologically. RESULTS: Plasma levels of
      SP and NPY did not significantly differ between patients with psoriasis and
      controls (median SP: 52.8 and 57.9 pg/ml, respectively; P = 0.32; median NPY: 8.5
      and 8.2 pg/ml, respectively; P = 0.67). CGRP plasma concentration was
      significantly elevated in psoriatic individuals both before (median 43.1 pg/ml)
      and after treatment (median 45.4 pg/ml), in comparison with healthy donors
      (median 13.5 pg/ml; P < 0.01 and P = 0.03, respectively). Treatment did not
      significantly influence plasma CGRP levels (P = 0.3). Median VIP plasma
      concentration in psoriatics before treatment was significantly higher compared
      with healthy controls (medians 66.9 and 60.1 pg/ml, respectively; P = 0.04), but
      the therapy resulted in significant decrease in VIP plasma level (median 19.0
      pg/ml; P < 0.001). In psoriatic patients significant correlations were noted
      between NPY and VIP (R = 0.34; P < 0.01), and VIP and CGRP plasma levels, both
      before (R = 0.28; P = 0.03) and after the treatment (R = 0.44; P < 0.01).
      CONCLUSIONS: Based on our results and previous literature data it could be
      suggested that neuropeptides may be involved in the development of psoriatic
      lesions.

PMID- 17437486
TI  - Carboxyfullerenes localize within mitochondria and prevent the UVB-induced
      intrinsic apoptotic pathway.
AB  - Carboxyfullerenes (CF) act as free radical scavengers in many cell settings and
      prevent apoptosis in vitro and in vivo. CF protect normal human keratinocytes
      from UVB-induced apoptosis, although the mechanisms underlying this effect remain
      to be clarified. Double-staining confocal laser microscopy revealed that CF
      penetrate the cell and colocalize with cytokeratin-18 within cytoplasm. This
      localization was confirmed by transmission electron microscopy that showed CF
      intermingled with keratin filaments. Moreover, double-staining with the
      mitochondrial marker anti-F1-ATPase antibody demonstrated that CF are expressed
      in mitochondria. Transmission electron microscopy confirmed that CF actually
      localize within mitochondria. Then, normal human keratinocytes were UVB
      irradiated in the presence or absence of CF at different doses. CF protected
      keratinocytes from apoptosis induced by reactive oxygen species. CF scavenging
      effect is associated with a partial blockade of the UVB-induced intrinsic
      apoptotic pathway by down-modulating caspase-9 activation and cytochrome c
      release, and by inhibiting the down-regulation of the inhibitor of apoptosis
      proteins (IAP) survivin, livin, IAP-1 and IAP-2. Finally, CF prevented the
      cleavage of Bid, up-regulation of Bad and down-regulation of Mcl-1 induced by
      UVB. Taken together, these results indicate that CF penetrate human
      keratinocytes, localize within mitochondria where they act both by scavenging
      free radicals and by protecting cells from apoptosis.

PMID- 17437487
TI  - Reversible transfection of human melanocytes mediated by Cre/loxP site-specific
      recombination system and SV40 large T antigen.
AB  - OBJECTIVE: To study the reversible transfection of human melanocytes mediated by
      simian virus 40 large T antigen (SV40LTAg) and Cre/loxP site-specific
      recombination system. METHODS: The reconstructed SV40LTAg-EGFP-neo-loxP vector
      was transfected into primary cultured human melanocytes with Sofast(TM)
      transfection reagent and the positive cells were selected using G418. After
      expanding culture of these positive cell clones, the expression of SV40LTAg was
      detected by polymerase chain reaction (PCR), reverse transcription-polymerase
      chain reaction (RT-PCR) and immunofluorescent method. After that, these positive
      cells were infected by virus supernatant of Cre-ER(T2) retrovirus vector and Cre
      recombinase was induced to act by tamoxifen. On the 6th and 10th day after Cre
      recombinase acting, the expression of SV40LTAg was detected using the same
      methods as above, and cell tumorigenicity was studied using soft agar assay,
      athymic mouse study and karyotype analysis. On 10th day after tamoxifen
      treatment, cell biological characters were identified with immunofluorescent
      staining and transmission electron microscopy. Then these cells were transplanted
      into vitiligo animal model to observe their melanogenesis ability in vivo.
      RESULTS: The genome DNA and total RNA were isolated from the positive cells
      transfected by SV40LTAg (designated as MCT) and specific 288 bp fragment was
      amplificated using PCR and RT-PCR methods. The results of immunofluorescence
      confirmed the expression of SV40LTAg in cell nucleus. On the 6th day after
      tamoxifen treatment in infected cells by Cre-ER(T2) retrovirus vector (designated
      as MCT-Cre), there could be detected SV40LTAg expression, but on 10th day, there
      could not be detected SV40LTAg expression in cells. These results showed that the
      excised efficiency of Cre recombinase increased along with time prolongation, and
      would obtain complete recombination efficiency. The identification of MCT-Cre
      cell biological characters showed that these cells had normal parent-cell-like
      cell phenotype and no tumorigenicity in vitro. The pigmentation started in 4
      weeks and formed black macula in 3 months after grafting. The pathological
      results showed that there had been significant melanocytes and melanin
      accumulation in epidermis and some hair follicle in transplanted area, which
      confirmed that MCT-Cre had melanogenesis function in vivo. CONCLUSION: Human
      melanocytes could be mediated by reversible transfection by SV40LTAg and Cre/loxP
      site-specific recombination system, which had stable parent-cell-like phenotypic
      characters and no tumorigenicity in vitro; moreover, these cells still had
      melanogenesis function in vivo.

PMID- 17437488
TI  - The expression pattern of prostaglandin E synthase and EP receptor isoforms in
      normal mouse skin and preinvasive skin neoplasms.
AB  - Prostaglandin (PG) E(2), the predominant PG in skin, accumulates in
      experimentally produced mouse skin tumors. PGE(2) induces proliferation of mouse
      keratinocytes in vitro, epidermal hyperplasia and dysplasia, a promoted epidermis
      phenotype, and angiogenesis in keratin 5 promoter (K5) cyclooxygenase (COX)-2
      transgenic NMRI mouse skin in vivo. PGE(2) is synthesized by COX-catalysed
      oxygenation of arachidonic acid to PGH(2) and its conversion to PGE(2) by
      prostaglandin E synthase (PGES) isoforms. PGE(2) signals via PGE(2) receptor
      isoforms EP1-EP4. Here, we investigated the expression profiles of PGES and EP
      receptors in wild type NMRI mouse skin constitutively expressing COX-1 when
      compared with the hyperplastic/dysplastic skin of homozygous K5 COX-2-transgenic
      mice and papillomas of both genotypes, which, in addition to COX-1, overexpress
      COX-2. The three PGES are constitutively expressed in normal and transgenic skin
      independent of the COX expression status. In papillomas, the increased PGE(2)
      levels correlate with an increased expression of mPGES-1 and cPGES. All four EP
      receptors were expressed in normal and transgenic skin. Only EP3 was slightly
      increased in transgenic skin. In papillomas of both genotypes, the expression
      levels of EP1 and EP4 were low when compared with those in wild type back skin.
      EP2 was the predominant receptor in papillomas of wild type and transgenic mice.
      In papillomas of wild type mice EP3 levels were slightly elevated when compared
      with transgenic tumors. EP1 and EP2 were localized in basal keratinocytes,
      sebaceous glands and CD31-positive vessels. Thus, normal and preinvasive mouse
      skin express the complete protein repertoire for PGE(2) biosynthesis and
      signalling.

PMID- 17437489
TI  - Identification of type I interferon-associated inflammation in the pathogenesis
      of cutaneous lupus erythematosus opens up options for novel therapeutic
      approaches.
AB  - Cutaneous lupus erythematosus (CLE) is one of the most common dermatological
      autoimmune disorders worldwide. Recently, several studies provided evidence for a
      pathogenic role of type I interferons (IFNs) in this disease. Plasmacytoid
      dendritic cells are major type I IFN producers in CLE skin lesions. Type I IFNs
      are able to induce the expression of several proinflammatory chemokines,
      including CXCL9 and 10, and enhance the cytotoxic capacity of infiltrating cells.
      Additionally, adhesion molecules and chemokine receptors, such as intercellular
      adhesion molecule-1, cutaneous lymphocyte antigen, E-selectin, CCR4 and CXCR3,
      are involved in the recruitment of potentially autoreactive lymphocytes into the
      skin. Here, we review the role of type I IFNs, adhesion molecules and chemokine
      receptors in CLE and discuss options for novel therapeutic approaches.

PMID- 17437490
TI  - The role of circulatory assistance and heart transplantation in Chagas' disease
      cardiomyopathy.

PMID- 17437491
TI  - The mexican peritoneal dialysis model: a personal reflection.

PMID- 17437492
TI  - Left ventricular circulatory support as bridge to heart transplantation in
      Chagas' disease cardiomyopathy.
AB  - This study was performed to assess the safety and feasibility of the implantation
      of ventricular assist devices (VADs) as a bridge to heart transplantation in
      patients with advanced biventricular failure due to Chagas' disease. Six patients
      were submitted to paracorporeal left VAD implantation, while right ventricular
      dysfunction was managed clinically. The mean time of circulatory support was 27
      days. Two patients were bridged to heart transplantation successfully, while the
      other four patients died under assistance with complications that correlated with
      the final situation of multiple organ failure. Nevertheless, persistent right
      ventricular dysfunction was observed only in one patient who survived more than
      15 days, despite the general significant preoperative compromise of the right
      ventricle. This paradoxical observation indicates that left VAD implantation may
      be regarded as a valuable treatment option for patients with Chagas' disease
      cardiomyopathy who evolve with decompensated heart failure or cardiogenic shock.

PMID- 17437493
TI  - Cardiac magnetic resonance in Chagas' disease.
AB  - American trypanosomiasis (Chagas' disease [CD]) caused by Trypanosoma cruzi is
      endemic in Latin America, where it is one of the leading causes of death. The
      involvement of the heart is crucial in the patients' prognosis. Besides
      lymphocytic myocarditis, cardiomyopathy is associated with several degrees of
      myocardial fibrosis (MF). Myocardial delayed enhancement by cardiac magnetic
      resonance (CMR) has been considered the most accurate method to detect MF in
      ischemic and nonischemic cardiomyopathy, including Chagas' heart disease.
      Additionally, CMR offers a wide variety of imaging tools to evaluate in detail
      morphology, the function and other tissue characterization abilities, such as
      detection of edema and fat. The present article aims to discuss the current
      clinical applicability of CMR to evaluate CD. We also discuss its future as a
      screening tool for very early myocardial involvement, which would allow the
      investigation of new therapeutic methods with potential influence in the natural
      history of CD.

PMID- 17437494
TI  - Allogenous bone grafts improved by bone marrow stem cells and platelet growth
      factors: clinical case reports.
AB  - In order to increase the amount of available bone where dental implants must be
      placed, the present study has associated platelet-rich plasma (PRP) and
      mononuclear cells (MNCs) from bone marrow aspirate and bone scaffold (BS) in 32
      patients aged between 45 and 75 years old. The MNC attainment and the adherence
      to the BS were confirmed through histology, cell culture, and scanning electron
      microscopy. The clinical results, analyzed by computed tomography, have showed
      that the scaffolds were well integrated and adapted to the cortical bone. We can
      conclude that the process of healing observed in the patients was due to the
      presence of mesenchymal stem cell in MNC fraction in the bone grafts.

PMID- 17437495
TI  - Adenoviral expression of calmodulin antisense reduces hypertrophy in cultured
      cardiomyocytes.
AB  - Sustained myocardial hypertrophy is associated with an increased risk of sudden
      death and progression to heart failure. Multiple signal pathways are involved in
      cardiac hypertrophy and understanding their interaction may point to new
      therapeutic targets. In this work, we tested the hypothesis that adenovirus
      mediated calmodulin (CaM) antisense expression will reduce the intracellular
      availability of CaM and inhibit the hypertrophic response. Three recombinant
      adenoviruses were constructed: AdASCaM, containing the AntiSense sequence of CaM
      and the enhanced green fluorescent protein (GFP) coding sequence; AdCaM,
      containing the coding sequence of CaM and the GFP sequence; and the AdGFP,
      containing the GFP coding sequence. Neonatal rat ventricular cardiomyocytes were
      infected with AdASCaM, AdCaM, or AdGFP and stimulated with phenylephrine (PE, 50
      microM) or angiotensin II (AngII, 10 microM) for 48 h and cell surface area
      measured with planimetry. After PE treatment, the surface areas of cardiomyocytes
      infected with AdASCaM or AdGFP were 411 +/- 174.3 micro(2) and 832.6 +/- 372.3
      micro(2), respectively (P < 0.01). After AngII treatment, the surface areas of
      cardiomyocytes infected with AdASCaM or AdGFP were 441.5 +/- 149.2 micro(2) and
      726 +/- 328.3 micro(2), respectively (P < 0.01). Adenoviral expression of the CaM
      antisense (AdASCaM) significantly inhibited PE or AngII-induced cardiomyocyte
      hypertrophy. Cardiomyocytes infected with the AdCaM showed increased area when
      compared with those infected with the AdGFP. These results suggest that
      adenovirus-mediated changes in CaM expression may alter hypertrophy in cardiac
      myocytes.

PMID- 17437496
TI  - Lyophilized bovine pericardium treated with a phenethylamine-diepoxide as an
      alternative to preventing calcification of cardiovascular bioprosthesis:
      preliminary calcification results.
AB  - This study investigated the calcification process that occurred on chemically
      treated bovine pericardium substrata through tests with simulated body fluid
      solutions. The use of bovine pericardium bioprosthetic valves in heart valve
      surgery has a significant drawback due to the calcification processes. Thus, many
      routes such as chemical treatments in the substratum or the adoption of systemic
      therapies are considered in the literature with the intention to inhibit or to
      decelerate this process. The presented treatment using the two different
      phenetylamine-diepoxide solutions showed no effects on calcification experiments
      as showed by the tests. However, the lyophilized bovine pericardium samples,
      treated with both solutions, did not show any detectable phosphate deposits. The
      lyophilization of bovine pericardium before chemical treatments with cross-link
      agents as epoxy compounds may be an alternative to the conventional calcification
      prevention methods, but further investigations are recommended to check if the
      same behavior is found in all lyophilized systems.

PMID- 17437497
TI  - Pulse pressure respiratory variation as an early marker of cardiac output fall in
      experimental hemorrhagic shock.
AB  - Pulse pressure (DeltaPp) and systolic pressure (DeltaPs) variations have been
      recommended as predictors of fluid responsiveness in critically ill patients. We
      hypothesized that changes in DeltaPp and DeltaPs parallel alterations in stroke
      volume (SV) and cardiac output (CO) during hemorrhage, shock, and resuscitation.
      In anesthetized and mechanically ventilated mongrel dogs, a graded hemorrhage (20
      mL/min) was induced to a target mean arterial pressure (MAP) of 40 mm Hg, which
      was maintained for additional 30 min. Total shed-blood volume was then
      retransfused at a 40 mL/min rate. CO, SV, right atrial pressure (RAP), pulmonary
      artery occlusion pressure (PAOP), and continuous mixed venous oxygen saturation
      (SvO(2)) were assessed. Both DeltaPp and DeltaPs were calculated from direct
      arterial pressure waveform. Removal of about 9% of estimated blood volume
      promoted a reduction in SV (14.8 +/- 2.2 to 10.6 +/- 1.3 mL, P < 0.05). At
      approximately 18% blood volume removal, significant changes in CO (2.4 +/- 0.2 to
      1.5 +/- 0.2 mL/min, P < 0.05), DeltaPp (12.6 +/- 1.4 to 15.8 +/- 2.0%, P < 0.05),
      and SvO(2) (82 +/- 1.4 to 73 +/- 1.7%, P < 0.05) were observed. Alterations in
      MAP, RAP, PAOP, and DeltaPs could be detected only after each animal had lost
      over 36% of estimated initial blood volume. There was correlation between blood
      volume loss and SV, CO, and SvO(2), as well as between blood loss and MAP,
      DeltaPp, and DeltaPs. Blood volume loss showed no correlation with cardiac
      filling pressures. DeltaPp is a useful, early marker of SV and CO for the
      assessment of cardiac preload changes in hemorrhagic shock, while cardiac filling
      pressures are not.

PMID- 17437498
TI  - Comparing oxygen transfer performance between three membrane oxygenators: effect
      of temperature changes during cardiopulmonary bypass.
AB  - Recently, a new oxygenator (Dideco 903 [D903], Dideco, Mirandola, Italy) has been
      introduced to the perfusion community, and we set about testing its oxygen
      transfer performance and then comparing it to two other models. This evaluation
      was based on the comparison between oxygen transfer slope, gas phase arterial
      oxygen gradients, degree of blood shunting, maximum oxygen transfer, and
      diffusing capacity calculated for each membrane. Sixty patients were randomized
      into three groups of oxygenators (Dideco 703 [D703], Dideco; D903; and Quadrox,
      Jostra Medizintechnik AG, Hirrlingen, Germany) including 40/20 M/F of 68.6 +/-
      11.3 years old, with a body weight of 71.5 +/- 12.1 kg, a body surface area (BSA)
      of 1.84 +/- 0.3 m(2), and a theoretical blood flow rate (index 2.4 times BSA) of
      4.4 +/- 0.7 L/min. The maximum oxygen transfer (VO(2)) values were 313 mL
      O(2)/min (D703), 579 mL O(2)/min (D903), and 400 mL O(2)/min (Quadrox), with the
      D903 being the most superior (P < 0.05). Oxygen (O(2)) gradients were 320 mm Hg
      (D703), 235 mm Hg (D903), and 247 mm Hg (Quadrox), meaning D903 and Quadrox are
      more efficient versus the D703 (P < 0.05). Shunt fraction (Qs/Qt) and diffusing
      capacity (DmO(2)) were comparable (P = ns). Diffusing capacity values indexed to
      BSA (DmO(2)/m(2)) were 0.15 mL O(2)/min/mm Hg/m(2) (D703), 0.2 mL O(2)/min/mm
      Hg/m(2) (D903), and 0.18 mL O(2)/min/mm Hg/m(2) (Quadrox) with D903 outperforming
      D703 (P < 0.0005). During hypothermia (32.0 +/- 0.3 degrees C), there was a lower
      absolute and relative VO(2 )for all three oxygenators (P = ns). The O(2)
      gradients, DmO(2) and DmO(2)/m(2), were significantly lower for all oxygenators
      (P < 0.01). Also, Qs/Qt significantly rose for all oxygenators (P < 0.01). The
      oxygen transfer curve is characteristic to each oxygenator type and represents a
      tool to quantify oxygenator performance. Using this parameter, we demonstrated
      significant differences among commercially available oxygenators. However, all
      three oxygenators are considered to meet the oxygen needs of the patients.

PMID- 17437499
TI  - Dynamic characteristics of a magnetically levitated impeller in a centrifugal
      blood pump.
AB  - Centrifugal blood pumps that employ hybrid active/passive magnetic bearings to
      support noncontact impellers have been developed in order to reduce bearing wear,
      pump size, the power consumption of the active magnetic bearing, and blood
      trauma. However, estimates made at the design stage of the vibration of the
      impeller in the direction of passive suspension during pump operation were
      inaccurate, because the influence of both the pumping fluid and the rotation of
      the impeller on the dynamic characteristics was not fully recognized. The purpose
      of this study is to investigate the dynamic characteristics in a fluid of a
      magnetically levitated rotating impeller by measuring both the frequency response
      to sinusoidal excitation of the housing over a wide frequency range and the
      displacement due to input of a pulsatile flow during left ventricular (LV)
      assist. The excitation tests were conducted under conditions in which the
      impeller was levitated in either air or water, and with or without rotation. The
      experimental and analytical results indicate that vibration of the impeller due
      to the external force in water was decreased, compared with that in air due to
      the hydraulic force of water. The axial resonant frequency rose quadratically
      with rotational speed, and the tilt mode had two resonant frequencies while
      rotating due to the gyroscopic effect. With the pump inserted into a mock
      systemic circulatory loop, the dynamic stability of the impeller when pulsatile
      pressure was applied during LV assist was verified experimentally. The amplitudes
      of vibration in response to the pulsatile flow in the passively constrained
      directions were considerably smaller in size than the dimensions of initial gaps
      between the impeller and the pump housing.

PMID- 17437500
TI  - A nonsurgical technique for blood access in extracorporeal affinity adsorption of
      antibodies in rats.
AB  - Monoclonal antibodies for targeting cytotoxic conjugates to tumor cells are
      currently being evaluated together with extracorporeal affinity adsorption. The
      aim of the adsorption was to reduce undesired side effects in normal organs and
      to increase the tumor-to-normal tissue ratios. This technique is also applicable
      to several other therapeutic areas such as immune-mediated disorders, that is,
      autoimmunity, allergy, and transplantation rejection. We describe an improved
      technique for extracorporeal affinity adsorption of radiolabeled biotinylated
      antibodies in rats. Blood access is established through the tail artery and tail
      vein, without surgical insertion of permanent catheters. This technique is
      simple, does not require surgery, and causes only minimal stress to the animals.
      In addition, experiments can be carried out on several animals simultaneously.
      This new technique is of considerable benefit for studying extracorporeal
      affinity adsorption in rats, as experiments can be carried out with negligible
      anatomical and physiological interventions, compared to previously used
      techniques.

PMID- 17437501
TI  - Mechanical stress activates platelets at a subhemolysis level: an in vitro study.
AB  - A feasibility study is performed to quantify sheep platelets (PLTs) and to
      identify the relationship between PLT count and hemolysis as a consequence of
      mechanical stress. Six adult, healthy Dorset sheep have been used for in vitro
      blood sampling test procedures in a hemoresistometer device (HRM). In each
      experiment, blood of the same animal was exposed to six different shear rates.
      Free hemoglobin levels and PLT count for each shear rate were detected. In all
      animals (A-F), hemolysis increased significantly between the shear rates of 2325
      and 3100/s (P < 0.05) and the mean PLT count dropped immediately (contact, low
      shear) 40% in the beginning, between the shear rates of 0 and 775/s (P < 0.05).
      PLT count increased slightly as soon as hemolysis started. At higher shear rates,
      hemolysis increased and PLTs reduced further. Precise counting of PLTs indicates
      that PLTs are consumed dramatically at very low shear (by contact) and further by
      applied mechanical stress when hemolysis is obvious. A repetition of these tests
      with human blood could indicate species differences.

PMID- 17437502
TI  - Low uptake of colorectal cancer screening 3 yr after release of national
      recommendations for screening.
AB  - BACKGROUND: National guidelines recommending colorectal cancer (CRC) screening
      for average risk Canadians were released in 2001. The current study determined
      rates of CRC screening and predictors of screening 3 yr after the guidelines were
      released. METHOD: A population-based random digit dial telephone survey of 1,808
      Alberta men and women aged 50-74 yr assessed awareness about, and self-reported
      rates of, screening. RESULTS: More average risk women than men reported a recent
      screening with a home fecal occult blood test (FOBT) (14.0%vs 9.8%, P= 0.013) but
      men had slightly higher rates of screening endoscopy in the past 5 yr (4.3%vs
      1.6%, P= 0.003). Overall, only 14.3% of average risk adults (N = 1,476) were up
      to-date on CRC screening. Multivariable predictors of being up-to-date on CRC
      screening differed for men and women although a doctor's recommendation for
      screening was a strong predictor for both genders (men OR 5.0, 2.9-8.3, women OR
      3.8, 2.3-6.5). Screening for other cancers was also an important predictor in
      both men and women. CONCLUSION: Three years after the release of national
      guidelines, rates of screening among average risk adults aged 50-74 yr were very
      low. Public education programs and primary care interventions to specifically
      invite average risk adults for screening may be required to increase CRC
      screening rates.

PMID- 17437503
TI  - Therapeutic drug use in women with Crohn's disease and birth outcomes: a Danish
      nationwide cohort study.
AB  - BACKGROUND: Crohn's disease (CD) is associated with increased risk of adverse
      birth outcomes. However, existing studies have not taken into account the impact
      of drug treatment. We examined the impact of drug treatment on birth outcomes-
      low birth weight (LBW), preterm birth, LBW at term, and congenital abnormalities
      (CAs)--among CD women. METHODS: A nationwide Danish cohort study of 900 children
      born to CD women between 1996 and 2004, based on the National Registry of
      Patients, the Birth Registry, and the nationwide prescription database.
      Pregnancies were classified according to receipt of prescriptions for CD
      medication: no drugs (reference group), 5-aminosalicylic acid (5
      ASA)/sulfasalazine, steroids, and azathioprine (AZA)/6-mercaptopurine (6-MP). We
      used logistic regression analyses to estimate the relative risk of birth outcomes
      with 95% confidence intervals. We used a proxy measure for disease activity.
      RESULTS: Preterm births were more prevalent among steroid- and AZA/6-MP-exposed
      women (12.3% and 25%, respectively) compared with the reference group (6.5%). CAs
      were more prevalent among AZA/6-MP-exposed compared with reference group (15.4%vs
      5.7%). Among steroid exposed, the risk of preterm birth was 1.4 (95% CI 0.6-3.3).
      Among AZA/6-MP exposed, the risk of preterm birth and CAs was 4.2 (95% CI 1.4
      12.5) and 2.9 (95% CI 0.9-8.9), respectively. CONCLUSIONS: The relative risk of
      adverse birth outcomes among CD women varied by type of drugs prescribed during
      pregnancy. The risk of preterm birth and CAs was greater when AZA/6-MP was
      prescribed, even after adjusting for confounders. However, further information is
      needed to determine whether the associations are causal.

PMID- 17437504
TI  - Clustering of inflammatory bowel disease with immune mediated diseases among
      members of a northern california-managed care organization.
AB  - BACKGROUND AND AIMS: Previous studies provide evidence that some immune-mediated
      diseases occur at greater frequency among inflammatory bowel disease (IBD)
      patients than in the general population. The present study examined the co
      occurrence of IBD with common immune-mediated disorders including asthma,
      psoriasis, type 1 diabetes, rheumatoid arthritis, multiple sclerosis, systemic
      lupus erythematosus, vitiligo, autoimmune thyroiditis (Grave's and Hashimoto's),
      and chronic glomerulonephritis. METHODS: We conducted a cross-sectional study
      among members of the Kaiser Permanente Medical Care Program for the period 1996
      2005. A total of 12,601 patients with at least two IBD diagnoses in computerized
      visit data were ascertained. Four persons without IBD were matched to each IBD
      patient on age, gender, and length of enrollment. Information on co-occurring
      diseases was obtained from computerized visit data for 1996-2005. Conditional
      logistic regression was used to estimate the odds ratio and 95% confidence
      interval for the association of IBD with immune-mediated disorders after
      adjusting for smoking. RESULTS: Seventeen percent of the IBD patients and 10% of
      the persons without IBD had a diagnosis for at least one immune-mediated disease.
      IBD patients were more likely to have asthma (1.5, 95% CI 1.4-1.6), psoriasis
      (1.7, 95% CI 1.5-2.0), rheumatoid arthritis (1.9, 95% CI 1.5-2.3), and multiple
      sclerosis (2.3, 95% CI 1.6-3.3). CONCLUSIONS: Among the immune-mediated diseases
      we studied, most were more common in IBD patients than in persons without IBD,
      suggesting that IBD shares common etiologic factors with other immune-mediated
      diseases.

PMID- 17437506
TI  - The effects of the number of rubber bands placed at each endoscopic session upon
      variceal outcomes: a prospective, randomized study.
AB  - AIM: To determine the role of the number of bands placed per session upon patient
      related and procedural-related outcomes. METHODS: Patients were assigned to
      receive as many bands as could be possibly placed (group 1) or up to a maximum of
      six bands (group 2) per session. The primary outcome measured was the number of
      sessions to achieve obliteration. Other outcomes measured included: rebleeding,
      variceal recurrence, mortality (within 6 wk and within 1 yr), complications,
      banding and total procedure times, and number of bands misfired. RESULTS: A total
      of 86 patients were enrolled: 45 in group 1 and 41 in group 2. The two groups had
      similar age, Child-Pugh scores, grade of varices at entry. The overall proportion
      of patients achieving obliteration was 56% (53% and 59% for groups 1 and 2,
      respectively). Despite receiving significantly more mean bands per session,
      patients in group 1 required similar (mean +/- SEM) number of sessions to
      obliteration (2.9 +/- 0.3 vs 3.3 +/- 0.3) and total number of bands (20.0 +/- 2.4
      vs 16.6 +/- 1.8) to achieve this goal compared with group 2. The overall
      proportion of patients with variceal rebleeding was 25%, the 1-yr variceal
      recurrence 31.3%, and the overall early- and 1-yr mortality were 18.6% and 33.7%,
      respectively. These proportions were similar in the two groups. Banding and total
      procedure times were significantly longer and associated with significantly more
      misfired bands per session in group 1. CONCLUSION: Compared with a maximum of six
      bands per session, the placement of >6 bands per session was not associated with
      better patient outcomes but with significantly more prolonged banding and total
      procedure times and significantly more misfired bands.

PMID- 17437505
TI  - Predictors of medication adherence in inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: This study reports cross-sectional medication adherence data
      from year 1 of the Manitoba Inflammatory Bowel Disease (IBD) Cohort Study, a
      longitudinal, population-based study of multiple determinants of health outcomes
      in IBD in those diagnosed within 7 yr. METHODS: A total of 326 participants
      completed a validated multi-item self-report measure of adherence, which assesses
      a range of adherence behaviors. Demographic, clinical, and psycho-social
      characteristics were also assessed by survey. Adherence was initially considered
      as a continuous variable and then categorized as high or low adherence for
      logistic regression analysis to determine predictors of adherence behavior.
      RESULTS: Using the cutoff score of 20/25 on the Medication Adherence Report
      Scale, high adherence was reported by 73% of men and 63% of women. For men,
      predictors of low adherence included diagnosis (UC: OR 4.42, 95% CI 1.66-11.75)
      and employment status (employed: OR 11.27, 95% CI 2.05-62.08). For women,
      predictors of low adherence included younger age (under 30 versus over 50 OR
      3.64, 95% CI 1.41-9.43; under 30 vs. 40-49 yr: OR 2.62, 95% CI 1.07-6.42). High
      scores on the Obstacles to Medication Use Scale strongly related to low adherence
      for both men (OR 4.05, 95% CI 1.40-11.70) and women (OR 3.89, 95% CI 1.90-7.99).
      5-ASA use (oral or rectal) was not related to adherence. For women,
      immunosuppressant use versus no use was associated with high adherence (OR 4.49,
      95% CI 1.58-12.76). Low trait agreeableness was associated with low adherence (OR
      2.03, 95% CI 1.12-3.66). CONCLUSIONS: Approximately one-third of IBD patients
      were low adherers. Predictors of adherence differed markedly between genders,
      although obstacles such as medication cost were relevant for both men and women.

PMID- 17437507
TI  - Hygiene could affect GERD prevalence independently: a population-based study in
      Tehran.
AB  - OBJECTIVE: Population-based data on gastroesophageal reflux disease (GERD) in
      Iran are limited. Current study is going to determine the prevalence of GERD in
      Tehran, Iran, and its association with potential risk factors. METHODS: In this
      cross-sectional study, a random clustered sample of Tehran province permanent
      households was selected from the latest postcodes. Data were collected by direct
      interview for each person aged 18-65 yr. GERD was defined as the existence of at
      least weekly episodes of heartburn and/or acid regurgitation during the last 6
      months. All participants were asked about past and recent sanitary conditions,
      oral hygiene, and smoking. Odds ratios and 95% confidence intervals (CI) were
      calculated using multivariable analysis. RESULTS: Interview was performed with
      2,561 eligible subjects (42.3% men). Response rate was 84.8%. The prevalence of
      GERD was 21.2% (95% CI 18.7-23.7). According to multivariable logistic regression
      analyses, individuals whose drinking water was obtained from well or tank during
      childhood were more prone to experience GERD symptoms (OR 1.54, 95% CI 1.03-1.77
      and OR 2.46, 95% CI 1.53-3.96, respectively). We also detected significant
      associations with increasing number of missing teeth (P value for linear trend =
      0.02) and history of unpurified water consumption during past 10 yr (P < 0.001).
      Current smokers had a higher prevalence of reflux (OR 1.82, 95% CI 1.32-2.51).
      CONCLUSION: The prevalence of GERD in our Iranian population was considerably
      higher than that reported from other Asian studies approaching western figures.
      GERD prevalence was significantly associated with the history of unpurified water
      consumption, poor sanitary conditions of childhood, number of missing teeth, and
      smoking in this population.

PMID- 17437508
TI  - Normal DXA bone mineral density but frail cortical bone in Turner's syndrome.
AB  - CONTEXT: Patients with Turner's syndrome have normal bone mineral density by dual
      energy X-ray absorptiometry (DXA), but a predisposition for fractures.
      Quantitative ultrasonography (QUS) measures cortical bone strength. OBJECTIVE: To
      compare QUS with DXA in patients with Turner's syndrome. PATIENTS AND METHODS:
      Twenty-seven Turner's syndrome patients, aged 21.1 +/- 6.3 years (mean +/- SD),
      were evaluated by DXA, measuring two-dimensional bone mineral density (BMD), and
      QUS, measuring speed of sound (SOS) of the radius and tibia. The results were
      compared to sex- and age-matched (Ctr A, n = 53) and height-matched (Ctr B, n =
      34) control groups. RESULTS: Fracture incidence per 1000 women years was 4.76 in
      Ctr A, 5 in Ctr B and 7.69 in Turner's patients. In Turner's syndrome patients,
      QUS results were significantly lower than in controls, whereas DXA Z-scores were
      not different from reference values. Correlation between tibia and radius SOS and
      height and age in controls (P < 0.0001) was not evident in Turner's syndrome.
      Oestrogen or growth hormone therapy had no effect on either QUS or DXA
      parameters. CONCLUSIONS: Bone fragility in Turner's syndrome is reflected by low
      SOS but not by DXA BMD. Low QUS, which assesses the cortical bone only, supports
      a defect in cortical bone in Turner's syndrome. Lack of SOS correlation with age,
      height and hormonal therapy in Turner's syndrome suggests a primary bone defect,
      rather than enhanced resorption of endocrine origin.

PMID- 17437509
TI  - Abnormal puberty in paediatric Cushing's disease: relationship with adrenal
      androgen, sex hormone binding globulin and gonadotrophin concentrations.
AB  - OBJECTIVE: Paediatric Cushing's disease is frequently associated with abnormal
      puberty. We addressed the hypothesis that prepubertal patients show excessive
      virilization and pubertal patients show suppression of LH and FSH secretion.
      DESIGN AND MEASUREMENTS: Serum androstenedione (A4), dehydroepiandrosterone
      sulphate (DHEAS), testosterone (T), and sex hormone binding globulin (SHBG) were
      determined at diagnosis and converted to standard deviation scores. LH, FSH
      concentrations were also determined. Severity of CD was assessed from the
      sleeping midnight cortisol concentration. Puberty was staged and excessive
      virilization defined as advance in pubic hair stage for breast stage or
      testicular volume (TV). PATIENTS: Twenty-seven CD patients (17 male, 10 female),
      median age 13.4 years (range 5.9-17.8) were studied. RESULTS: In the CD group as
      a whole, A4, DHEAS, T standard deviation scores (SDS) values were normal. SHBG
      SDS values (n = 19) were low (median -1.93, -4.32-0.86) correlating with BMI (r =
      -0.49). A4, DHEAS, T, SHBG, LH and FSH did not correlate with midnight cortisol,
      but A4 and T SDS correlated with ACTH at 09.00 h (both r = 0.51). Thirteen
      patients (11 male, 2 female) had excessive virilization with increased A4 (P =
      0.033), DHEAS (P = 0.008), testosterone (P = 0.033) and decreased SHBG (P =
      0.004) compared with subjects without excessive virilization. Pubertal boys (TV >
      or = 4 ml) (n = 7) and girls (breasts > or = stage 2) (n = 8) had low median LH
      and FSH. Boys had an LH concentration of 1.2 mU/l (0.3-3.5), FSH, 0.9 mU/l (0.2
      6.4) and median T SDS, -1.95 (-3.8-4.65), while girls had an LH concentration of
      1 mU/l (0.3-7.4). CONCLUSIONS: Many patients had abnormal puberty and excessive
      virilization associated with increased adrenal androgens and decreased SHBG.
      Pubertal patients had low LH and FSH suggesting impaired pituitary-gonadal axis
      function.

PMID- 17437510
TI  - Variability in hydrocortisone plasma and saliva pharmacokinetics following
      intravenous and oral administration to patients with adrenal insufficiency.
AB  - OBJECTIVE: The best method for determining hydrocortisone replacement therapy is
      not well defined. This study aimed to assess interindividual variability in
      cortisol pharmacokinetics and to investigate whether measurement of salivary
      cortisol provides a useful alternative to plasma concentration measurements.
      DESIGN: Intravenous (IV) and oral crossover. PATIENTS: Twenty-seven patients with
      primary or secondary adrenal insufficiency who had been on stable replacement
      therapy for at least 3 months. MEASUREMENTS: Plasma and salivary concentrations
      of cortisol were measured up to 8 h following administration of hydrocortisone.
      RESULTS: After IV administration, Cmax ranged from 715 to 8313 nmol/l, area under
      the curve (AUC) from 1112 to 12 177 nmol h/l and cortisol clearance had a median
      (range) of 0.267 (0.076-0.540) l/h/kg. After oral administration, Cmax ranged
      from 422 to 1554 nmol/l, AUC 1081-5471 nmol h/l and oral clearance had a median
      (range) of 0.267 (0.081-0.363) l/h/kg. There was no clear relationship between
      paired saliva and plasma cortisol concentrations after IV or oral dosing. Plasma
      and salivary AUC(2-8 h) after IV administration were highly correlated (r2 =
      0.77) but differences between predicted and measured plasma AUCs ranged from 3%
      to 90%. There was a poor correlation between plasma and saliva AUC(2-6 h) after
      oral administration (r2 = 0.16). CONCLUSIONS: The wide interindividual
      variability in plasma and salivary profiles of cortisol following the
      administration of IV and oral hydrocortisone to patients with adrenal
      insufficiency and the poor correlation between salivary and plasma measurements
      suggest that salivary cortisol measurements cannot be used for individual
      hydrocortisone dosage adjustment.

PMID- 17437511
TI  - Characteristics of cardiac and vascular structure and function in Prader-Willi
      syndrome.
AB  - OBJECTIVE: Prader-Willi syndrome (PWS) is a genetic obesity syndrome
      characterized by hyperphagia, behavioural disturbance and intellectual
      disability. PWS appears to be associated with a high incidence of sudden death,
      suspected to be cardiopulmonary in origin. We therefore sought to provide an
      assessment of cardiac and vascular structure and function in patients with PWS.
      PATIENTS: Nine patients with genetically confirmed PWS, mean age 28 years, body
      mass index (BMI) 42 kg/m2, were compared with nine age- and gender-matched lean
      controls. MEASUREMENTS: Lipid parameters, high-sensitivity C-reactive protein (hs
      CRP) and fasting glucose and insulin were measured. To assess cardiac structure
      and function, a resting electrocardiogram (ECG), exercise stress test, 24-h
      continuous ECG monitoring, and echocardiogram were obtained. Patients and control
      subjects also underwent comprehensive noninvasive vascular assessment, including
      venous-occlusion forearm plethysmography, brachial artery flow-mediated
      dilatation (FMD), radial artery tonometry and carotid intima-media thickness
      (IMT) measurements. RESULTS: All patients with PWS had significantly elevated hs
      CRP (> 3.0 mg/l) (mean 11.5 mg/l, median 11.47, interquartile range: 4.48-15.8
      mg/l), compared with controls (P < 0.001). Five of nine patients with PWS had
      subnormal exercise capacity (< 4 mets on exercise stress testing). Twenty-four
      hour ECG monitoring revealed prolonged sinus pauses in one patient, up to 4.8 s,
      requiring pacemaker insertion. Microvascular function as assessed by peak
      hyperaemic flow response was decreased in PWS (6.1 +/- 1.0 times baseline flow
      vs. controls 13.5 +/- 1.6 times baseline flow, P = 0.01). Other measures were
      similar between PWS and controls. CONCLUSIONS: This group of PWS patients had
      significantly raised levels of the inflammatory marker hs-CRP and evidence of
      microcirculatory dysfunction, both of which are associated with coronary artery
      disease and early sudden death. The sinus node dysfunction may in itself be a
      risk factor for sudden cardiac death.

PMID- 17437512
TI  - Variation in GH and IGF-I assays limits the applicability of international
      consensus criteria to local practice.
AB  - BACKGROUND: There is increasing reliance on consensus criteria for decision
      making. Recent criteria state that acromegaly is excluded by a nadir GH during an
      oral glucose tolerance test (OGTT) of < 1 microg/l and a normal level of IGF-I.
      OBJECTIVE: To study GH and IGF-I assay performance close to cut-off values for
      active acromegaly. DESIGN AND METHODS: Two serum samples known to give borderline
      results were sent to all centres participating in the UK National External
      Quality Assessment Service (NEQAS). Sample A was assigned to be a nadir during an
      OGTT and sent for GH assessment to 104 centres. Sample B, with a clinical
      scenario, was sent to 23 centres that measure IGF-I, and these centres were asked
      to measure IGF-I, interpret the result and provide the source of their reference
      ranges (RRs). RESULTS: For sample A, the median GH was 2.6 mU/l (range 1.04-3.5
      mU/l). Applying a conversion factor (CF) of 2.0 (1 microg/l = 2 mU/l), the most
      negatively biased method classified 10% of the values consistent with acromegaly,
      while the most positively biased method classified all values as consistent with
      the diagnosis. Applying a CF of 3.0 (1 microg/l = 3 mU/l), only 11% of results
      were consistent with acromegaly. For sample B, the median IGF-I was 50.8 nmol/l
      (range 24.3-60.9 nmol/l). All centres used age-related RRs. There was a 50%
      variation in the upper limit of the RRs between centres. Overall, 30% of the IGF
      I results were against the diagnosis. There was little agreement in the RRs
      quoted by centres using the same method. CONCLUSION: Variability in assay
      performance, coupled with use of inappropriate CFs and RRs, undermines the
      applicability of international consensus criteria to local practice.

PMID- 17437513
TI  - Menopausal hormone therapy and gallbladder disease: the Study of Health in
      Pomerania (SHIP).
AB  - OBJECTIVE: Several studies suggest that oral menopausal hormone therapy (MHT) is
      associated with an increased risk of gallbladder disease. It has been
      hypothesized that nonoral MHT may reduce the risk of cholelithiasis. The
      objective of the present study was to analyse the association between (1) use of
      life-time MHT (ever use) and gallbladder disease and (2) nonoral use of MHT and
      gallbladder disease. DESIGN: Cross-sectional study using population-based data
      from the Study of Health in Pomerania (SHIP). POPULATION: The study population
      included 994 postmenopausal women, aged 40-79 years. The subgroup of current oral
      and nonoral MHT users comprised 139 women. METHODS AND MEASUREMENTS:
      Sociodemographic, medical and reproductive characteristics were based on computer
      assisted personal interviews, and selected laboratory parameters were analysed.
      Gallbladder disease was defined by either a prior history of cholecystectomy or
      the presence of current sonographically diagnosed gallstones. Data analyses
      consisted of descriptive, bivariable and multivariable procedures. We performed
      Poisson regression with Huber/White standard errors to investigate the
      association between ever use, current nonoral use of MHT and gallbladder disease.
      RESULTS: We found no significant association between ever use of MHT and
      gallbladder disease and sonographically diagnosed gallstones in fully adjusted
      analyses. Women who used MHT had a significantly higher risk for cholecystectomy
      compared to nonusers. There was no association between nonoral use of MHT and
      gallbladder disease. CONCLUSIONS: Our analyses do not lend support to the
      hypothesis that use of MHT is associated with gallbladder disease.

PMID- 17437514
TI  - Lack of electrocardiographic changes in women with polycystic ovary syndrome.
AB  - OBJECTIVE: The aim of the present study was to investigate the potential
      alterations in electrocardiographic (ECG) pattern in patients with polycystic
      ovary syndrome (PCOS). PATIENTS: Fifty PCOS patients and 50 age- and body mass
      index-matched healthy women were studied. METHODS: We assessed hormonal and
      metabolic pattern, and performed ECG analysis for evaluating PQ interval, QRS
      duration, minimum and maximum QT interval corrected for heart rate (QT(c)min and
      QT(c)max, respectively), corrected QT dispersion (QT(c)d), corrected J point/T
      wave interval (JTend(c)), corrected JTmax interval (JTmax(c)), and corrected Tmax
      end interval (Tmax-end(c)). RESULTS: QT(c)min (399 +/- 21 vs. 396 +/- 25 ms, P =
      0.51); QT(c) max (445 +/- 25 vs. 443 +/- 27 ms, P = 0.70); and QT(c)d (46 +/- 13
      vs. 47 +/- 15 ms, P = 0.72); JTend(c) (337 +/- 14 vs. 336 +/- 16 ms(1/2), P =
      0.74); and JTmax(c) (256 +/- 22 vs. 258 +/- 21 ms(1/2), P = 0.64); Tmax-end(c)
      (81 +/- 18 vs. 78 +/- 19 ms(1/2), P = 0.42) were not significantly different
      between PCOS and healthy women. CONCLUSION: Despite profound differences in
      hormonal and metabolic pattern, our data demonstrate no significant difference in
      ECG pattern in PCOS compared to healthy controls.

PMID- 17437515
TI  - Quantitative measurement of thyroid blood flow for differentiation of painless
      thyroiditis from Graves' disease.
AB  - OBJECTIVE: Differentiation between destruction-induced thyrotoxicosis and Graves'
      thyrotoxicosis is important for selection of proper therapy. It is, however,
      often difficult to make this distinction without measurement of radioactive
      iodine uptake. We investigated the possibility that assessment of thyroid blood
      flow would allow differentiation between the two entities. PATIENTS AND
      MEASUREMENTS: One hundred and fourteen untreated patients with thyrotoxicosis (56
      Graves' disease, 28 painless thyroiditis, 30 subacute thyroiditis) and 25 normal
      controls were examined. Serum levels of freeT4 (FT4), freeT3 (FT3) and TSH were
      measured by chemiluminescent immunoassay, and anti-TSH receptor antibodies (TSH
      binding inhibitory immunoglobulin, TBII) were measured by enzyme-linked
      immunosorbent assay. Thyroid volume and blood flow (TBF) were measured
      quantitatively by ultrasonography. RESULTS: TBF was significantly higher in
      Graves' disease (mean +/- 1SD: 14.9 +/- 6.4%, P < 0.0001) than in painless
      thyroiditis (0.8 +/- 0.5%), subacute thyroiditis (0.9 +/- 0.7%) and in normal
      controls (0.8 +/- 0.5%). All patients with Graves' disease had TBF values of more
      than 4% and all patients with painless thyroiditis and subacute thyroiditis had
      TBF values less than 4%. TBF values significantly correlated with values of
      radioactive iodine uptake (RAIU) either at 3 h (r = 0.492, P < 0.01) or 24 h (r =
      0.762, P < 0.001) within the Graves' disease and painless thyroiditis groups.
      There was no relationship between TBF values and thyroid volumes or values of
      TBII in the Graves' disease group. All patients with Graves' disease had positive
      TBII of 15% or more. Three of 28 patients with painless thyroiditis and one of 30
      patients with subacute thyroiditis had positive TBII. CONCLUSION: TBF was
      quantitatively measured by power Doppler ultrasonography and was more effective
      than TBII for differentiation between destruction-induced thyrotoxicosis
      (painless or subacute thyroiditis) and Graves' thyrotoxicosis. TBF values of less
      than 4% in untreated thyrotoxic patients are laboratory signals of destruction
      induced thyrotoxicosis and if these are determined, the radioactive iodine uptake
      test can be omitted for differential diagnosis of these two types of
      thyrotoxicosis.

PMID- 17437516
TI  - Genetic analysis of the PAX8 gene in children with congenital hypothyroidism and
      dysgenetic or eutopic thyroid glands: identification of a novel sequence variant.
AB  - OBJECTIVE: To analyse the coding region of PAX8 in individuals with congenital
      (CH) or post neonatal hypothyroidism due to dysgenetic (TD) or eutopic thyroid
      glands. DESIGN AND PATIENTS: Forty-three children with CH and TD (13 agenesis, 23
      ectopia, and seven hypoplasia), one subject with post neonatal onset of
      hypothyroidism and thyroid ectopia, 15 children with CH and eutopic thyroid
      glands and six euthyroid adults with thyroid hemiagenesis were enrolled as cases,
      along with 120 healthy individuals as controls. MEASUREMENTS: Exons 2-8 of the
      PAX8 were directly sequenced. HeLa and HEK293 cells were transfected with PAX8
      wild-type (PAX8-WT), mutant PAX8, p300, thyroid transcription factor 1 (TTF-1)
      and thyroglobulin promoter pGL3 (TG prom-pGL3). Synergism of TTF-1 with PAX8-WT
      vs. mutant and activity of PAX8-WT vs. mutant in accompaniment with p300 on TG
      prom-pGL3 were also assessed. The luminescence produced by PAX8-WT and mutant
      PAX8 was measured. RESULTS: Among patients and controls only a 15-year-old girl
      with thyroid ectopia showed a heterozygous transition of cytosine to thymine at
      position 674 in exon 6, which changed a conserved threonine at position 225 to
      methionine (PAX8-T225M). Her father and sister harboured PAX8-T225M without
      abnormal thyroid phenotypes. PAX8-T225M and PAX8-WT similarly increased
      luciferase activity and had a similar synergistic effect with TTF-1. At 500 ng
      p300, however, PAX8-T225M could not significantly increase TG promoter activity
      when compared to PAX8-T225M alone, while PAX8-WT +500 ng p300 induction was
      significantly higher than PAX8-WT alone (P < 0.001). Cotransfection of TTF-1
      together with PAX8-T225M resulted in rescuing of the lack of synergism with p300.
      CONCLUSIONS: PAX8 mutations in congenital hypothyroidism due to dysgenetic or
      orthotopic thyroid glands are rare. PAX8-T225M is probably a rare variant.

PMID- 17437517
TI  - Thyroid cysts: a new extra-adrenal site of aldosterone synthase expression and
      increased aldosterone content.
AB  - BACKGROUND: The rapid re-accumulation of fluid following aspiration of thyroid
      cystic lesions suggests that active transport of sodium and water may be involved
      in volume regulation of these lesions. In this study we address the possibility
      that aldosterone may take part in this process. SUBJECTS AND METHODS: Thirty-one
      patients (29 women and two men), with a mean age of 52.7 +/- 13.2 years (range:
      27-77 years) underwent evaluation for thyroid nodules that had a sonographic
      cystic component. Cystic fluid obtained by FNA biopsy was sent for cytological
      examination and biochemical measurements. In 10 patients, material was collected
      for RNA extraction and determination of aldosterone synthase expression by RT-PCR
      amplification. RESULTS: All lesions were benign, cystic, colloid nodules. Cyst
      fluid aldosterone levels as measured by routine radioimmunoassay (RIA) were
      elevated above the normal plasma levels in all but five patients. Mean
      aldosterone levels were 27.1 +/- 22.9 ng/dl (SD) (range: 5.9-117.5 ng/dl). In
      contrast, cyst cortisol values were in the low, low normal serum range (6.2 +/-
      2.9 microg/dl, range: 0.2-10.2 microg/dl). Sodium, chloride and potassium levels
      were 137 +/- 4.7 mEq/l, 98 +/- 5 mEq/l and 4.9 +/- 1.4 mEq/l, respectively.
      Plasma aldosterone levels were normal in all patients tested. To confirm these
      results, 12 samples were assayed after extraction and chromatography using a
      highly specific antibody. Cyst aldosterone levels in this group were elevated
      above the normal serum range in all but one patient (mean concentration: 24.5 +/-
      14.6 ng/dl, range: 8.72-40.1 ng/dl). In this group, 18(OH)B levels were within
      the normal plasma range (12-55 ng/dl) in all but one patient (34.9 +/- 17 ng/dl).
      Furthermore, aldosterone synthase mRNA expression was found in aspirates of four
      of 10 patients. CONCLUSIONS: The increased aldosterone concentration and the
      presence of aldosterone synthase expression suggest that aldosterone may be
      locally produced and secreted in thyroid tissue. The pathophysiological
      implications of this finding remain to be established.

PMID- 17437518
TI  - Intraoperative parathyroid hormone assay improves outcomes of minimally invasive
      parathyroidectomy mainly in patients with a presumed solitary parathyroid adenoma
      and missing concordance of preoperative imaging.
AB  - OBJECTIVE: Intraoperative parathyroid hormone assay (IOPTH) is often used during
      minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism
      (pHPT). However, several investigators have reported conflicting outcomes,
      throwing doubt on the real influence of this adjunct on surgical decision-making.
      The aim of this study was to determine the impact of routine use of IOPTH on the
      success rate of MIP as the primary outcome, and whether it value-added to
      surgical decision-making during the operations at our institution. DESIGN: The
      results of MIP were determined on postoperative follow-up in 177 consecutive
      patients with pHPT and compared with the results of preoperative imaging,
      findings at surgery and the value-added accuracy of IOPTH in surgical decisions.
      PATIENTS: All 177 patients had biochemically documented pHPT and all were
      referred for first-time surgery. MEASUREMENTS: Group 1 patients (n = 62)
      underwent a unilateral neck exploration (UNE) without IOPTH, and group 2 patients
      (n = 115) underwent MIP (either video-assisted or open) with IOPTH. The primary
      outcome was the cure rate, whereas the secondary outcome was the value-adding of
      IOPTH to surgical decision-making during MIP. RESULTS: Of the group 1 vs. 2
      patients, 57/62 (91.9%) vs. 114/115 (99.1%) were cured (P = 0.01). Five (8.1%) of
      the group 1 patients were hypercalcaemic postoperatively, owing to an additional,
      overlooked, hyperfunctioning parathyroid gland, whereas among the 115 group 2
      patients, 104 (90.4%) underwent resection of a single parathyroid adenoma, met
      the Miami criterion, and were cured. The remaining 11 (9.6%) patients did not
      have an adequate reduction in parathyroid hormone levels and underwent further
      neck exploration, with resection of additional hyperfunctioning parathyroids in
      nine of them. One group 2 patient was not cured. However, a decrease of less than
      50% of intraoperative parathyroid hormone (iPTH) assay correctly identified the
      risk of persistent disease in that patient. Another patient in group 2 had a
      false-negative IOPTH result. The value-added accuracy of IOPTH (correct assay
      based surgeon's decision of further neck exploration) was demonstrated in 3 of 78
      group 2 patients with concordant results of both imaging studies vs. 7 of 37
      group 2 patients with only one positive imaging study, or 3.8 vs. 18.9% of
      patients (P = 0.007). CONCLUSIONS: Routine use of IOPTH significantly improves
      cure rates of MIP in comparison to open image-guided UNE without IOPTH. It is a
      valuable adjunct in surgical decision-making, allowing for intraoperative
      recognition and resection of additional hyperfunctioning parathyroid tissue
      missed by preoperative imaging studies. IOPTH offers substantial value-adding to
      surgical decision-making, particularly in patients with only one positive imaging
      study result, and significantly improves the success rate of MIP in these
      patients. However, in patients with concordant results of two imaging studies,
      the assay offers significantly lower value-adding to surgical decisions, as a
      vast majority of patients are cured after removal of a two-image-indexed
      parathyroid lesion. Despite this, we strongly advocate routine use of IOPTH in
      all patients undergoing MIP, as this adjunct offers maximum safety for the
      patient and confidence for the surgeon.

PMID- 17437519
TI  - Reduced maternal corticosteroid-binding globulin and cortisol levels in pre
      eclampsia and gamete recipient pregnancies.
AB  - OBJECTIVE: To measure and contrast maternal cortisol and corticosteroid-binding
      globulin (CBG) levels in pregnancies with normal outcomes, pre-eclampsia,
      intrauterine growth restriction (IUGR) and in gamete recipients. STUDY DESIGN:
      Prospective study of 93 women at high risk of pre-eclampsia, including gamete
      recipients (n = 22) and 33 controls. Plasma total and free cortisol and CBG were
      measured every 2 weeks from 16 weeks' gestation until delivery. RESULTS: Forty
      two per cent of the high-risk group had complications, including pre-eclampsia (n
      = 11), gestational hypertension (n = 16) and small-for-gestational-age (SGA)
      neonates (n = 12). There were no complications in the controls. In all groups,
      plasma CBG concentrations increased progressively across gestation (P < 0.05), in
      parallel to total cortisol, but fell significantly from 36 weeks' gestation
      onwards, with a corresponding rise in free cortisol concentrations. In pre
      eclampsia and gestational hypertension, plasma CBG, and total and free cortisol
      concentrations were lower from 36 weeks onwards (P < 0.05). In IUGR, plasma CBG
      concentrations were suppressed from 28 weeks' gestation until delivery (P <
      0.05), but with no significant difference in plasma total and free cortisol.
      Gamete recipients had significantly lower plasma CBG from 20 weeks' gestation
      onwards, and plasma total and free cortisol were reduced at 24 and 32 weeks
      onwards, respectively. CONCLUSIONS: Maternal plasma CBG, total and free cortisol
      concentrations are reduced in pre-eclampsia/gestational hypertension, and
      markedly reduced in gamete recipients. Low CBG may be due to reduced synthesis or
      enhanced inflammation-driven degradation. Low maternal cortisol may be due to a
      lack of placental corticotropin-releasing hormone or reduced maternal ACTH,
      driving cortisol production. Low maternal cortisol may influence the foetal
      hypothalamic-pituitary-adrenal axis and disease patterns later in life following
      complicated pregnancy.

PMID- 17437520
TI  - The adaptation and relationship of FGF-23 to changes in mineral metabolism in
      Graves' disease.
AB  - OBJECTIVE: The aim of this study was to observe the changes in bone and mineral
      metabolism and to confirm the regulation of fibroblast growth factor-23 (FGF-23)
      in untreated Graves' disease. PATIENTS AND MEASUREMENTS: The study comprised 39
      patients, with or without Graves' disease. The Graves' disease group was made up
      of 21 newly diagnosed patients, enrolled before starting treatment. Their disease
      was determined by biochemical and radiological means. The control group was
      composed of 18 people who were proven to be euthyroid without any diseases
      affecting bone and mineral metabolism. FGF-23, calcium, phosphate, PTH, 25
      hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels and
      bone turnover markers were compared between these groups. RESULTS: Serum calcium
      and phosphate, plasma FGF-23 and free T4 were significantly higher in the Graves'
      disease group than in the healthy control group (P < 0.05). The bone turnover
      markers serum osteocalcin and C-terminal cross-linked telopeptide of type 1
      collagen (s-CTx) were also significantly elevated in the Graves' disease group,
      and had a positive correlation with free T4 levels. However, there was no
      significant decrease in PTH and 1,25(OH)2D in the Graves' disease group. Plasma
      levels of FGF-23 exhibited a positive correlation with serum phosphate levels and
      with free T4 levels (P < 0.05). CONCLUSIONS: These findings suggest that FGF-23
      is physiologically related to serum phosphate homeostasis, as indicated
      indirectly by the changes in bone and mineral metabolism, in untreated Graves'
      disease.

PMID- 17437521
TI  - Differences between endocrinologists and endocrine surgeons in management of the
      solitary thyroid nodule.
AB  - BACKGROUND: It is not known whether management of the solitary thyroid nodule
      differs between endocrinologists and endocrine surgeons. METHODS: A questionnaire
      containing a hypothetical case (a 42-year-old euthyroid woman with a 2-x-3-cm
      solitary thyroid nodule) and 13 clinical variations was sent to endocrinologists
      and endocrine surgeons in Australia. RESULTS: The response rate was 51%,
      including 122 endocrinologists and 48 endocrine surgeons. For the index case,
      serum thyroid-stimulating hormone (TSH), fine needle aspiration biopsy (FNAB) and
      ultrasonography were widely used by both groups, but thyroid antibody tests and
      scintigraphy were ordered more commonly by endocrinologists. In the setting of
      benign cytology, treatment differed significantly between specialties for the
      index case (endocrinologists: no treatment 78%, surgery 11%, thyroxine 11%;
      surgeons: no treatment 73%, surgery 25%, thyroxine 2%; P = 0.032). Treatment
      recommendations also differed significantly for 12 of the 13 clinical variations.
      In particular, for a patient with a suppressed serum TSH concentration, a
      majority of endocrinologists recommended radioiodine treatment, whereas surgeons
      favoured surgery (endocrinologists: radioiodine 53%, surgery 22%, no treatment
      25%; surgeons: surgery 60%, radioiodine 11%, no treatment 27%; P < 0.001). For
      most of the variations, a higher proportion of surgeons than endocrinologists
      recommended surgical treatment. Comparison with previous surveys of European
      Thyroid Association and American Thyroid Association members (predominantly
      endocrinologists) demonstrated considerable international differences in
      management. CONCLUSION: There are clinically significant differences between
      Australian endocrinologists and endocrine surgeons in management of the solitary
      thyroid nodule, and international differences in management of this disorder.

PMID- 17437522
TI  - Biochemical characterization of the recombinant human Nogo-A ectodomain.
AB  - Nogo-A is a physiologically relevant inhibitor of neuronal growth and
      regeneration in the myelin of the adult human central nervous system and has
      attracted considerable attention as a molecular target for the treatment of
      spinal cord injuries. To gain insight into the structural and functional
      properties of the large extramembrane region that is characteristic for the Nogo
      A splice form of this member of the Reticulon family of membrane proteins, we
      cloned and expressed the region comprising residues 334-966 as a soluble
      homogeneous protein in the periplasm of Escherichia coli. SDS/PAGE, under
      nonreducing conditions, and a systematic substitution analysis of all six Cys
      residues of Nogo-A indicated that this domain forms two structural disulfide
      bonds among Cys residues 424, 464, 559 and 597, whereas the Cys residues at
      positions 699 and 912 seem to be dispensable for folding. The occurrence of a hot
      spot for host cell proteases and a limited proteolysis experiment suggest that
      the N-terminal region of Nogo-A up to residue 373 is structurally disordered.
      Although analytical gel permeation chromatography revealed a large apparent
      molecular size for the recombinant Nogo-A fragment, indicating oligomer
      formation, data from analytical ultracentrifugation and dynamic light scattering
      support a stable monomeric quaternary structure. Notably, the CD spectrum is
      indicative of a high content of random coil, such that Nogo-A exhibits--at least
      in part--features of a natively unfolded protein. Nevertheless, the protein
      fragment identified in this study, as well as its biochemical analysis, provide a
      promising starting point for future investigations to track down globular
      subdomains and functionally important regions as well as putative receptor
      binding sites therein.

PMID- 17437523
TI  - Solution structure of an M-1 conotoxin with a novel disulfide linkage.
AB  - The M-superfamily of conotoxins has a typical Cys framework (-CC-C-C-CC-), and is
      one of the eight major superfamilies found in the venom of the cone snail.
      Depending on the number of residues located in the last Cys loop (between Cys4
      and Cys5), the M-superfamily family can be divided into four branches, namely M
      1, -2, -3 and -4. Recently, two M-1 branch conotoxins (mr3e and tx3a) have been
      reported to possess a new disulfide bond arrangement between Cys1 and Cys5, Cys2
      and Cys4, and Cys3 and Cys6, which is different from those seen in the M-2 and M
      4 branches. Here we report the 3D structure of mr3e determined by 2D (1)H NMR in
      aqueous solution. Twenty converged structures of this peptide were obtained on
      the basis of 190 distance constraints obtained from NOE connectivities, as well
      as six varphi dihedral angle, three hydrogen bond, and three disulfide bond
      constraints. The rmsd values about the averaged coordinates of the backbone atoms
      were 0.43 +/- 0.19 A. Although mr3e has the same Cys arrangement as M-2 and M-4
      conotoxins, it adopts a distinctive backbone conformation with the overall
      molecule resembling a 'flying bird'. Thus, different disulfide linkages may be
      employed by conotoxins with the same Cys framework to result in a more
      diversified backbone scaffold.

PMID- 17437524
TI  - Upregulation of endothelial adhesion molecules by lysophosphatidylcholine.
      Involvement of G protein-coupled receptor GPR4.
AB  - Lysophosphatidylcholine induces expression of adhesion molecules; however, the
      underlying molecular mechanisms of this are not well elucidated. In this study,
      the intracellular signaling by which lysophosphatidylcholine upregulates vascular
      cell adhesion molecule-1 and P-selectin was delineated using YPEN-1 and HEK293T
      cells. The results showed that lysophosphatidylcholine dose-dependently induced
      expression of vascular cell adhesion molecule-1 and P-selectin, accompanied by
      the activation of transcription factor nuclear factor kappaB. However, the
      nuclear factor kappaB inhibitor caffeic acid phenethyl ester (CAPE) and the
      antioxidant N-acetylcysteine only partially blocked lysophosphatidylcholine
      induced adhesion molecules. Subsequently, we found that the
      lysophosphatidylcholine receptor G protein-coupled receptor 4 (GPK4) was
      expressed in YPEN-1 cells and triggered the cAMP/protein kinase A/cAMP response
      element-binding protein pathway, resulting in upregulation of adhesion molecules.
      Further evidence showed that overexpression of human GPK4 enhanced
      lysophosphatidylcholine-induced expression of adhesion molecules in YPEN-1 cells,
      and enabled HEK293T cells to express adhesion molecules in response to
      lysophosphatidylcholine. In conclusion, the current study suggested two pathways
      by which lysophosphatidylcholine regulates the expression of adhesion molecules,
      the lysophosphatidylcholine/nuclear factor-kappaB/adhesion molecule and
      lysophosphatidylcholine/GPK4/cAMP/protein kinase A/cAMP response element-binding
      protein/adhesion molecule pathways, emphasizing the importance of the
      lysophosphatidylcholine receptor in regulating endothelial cell function.

PMID- 17437526
TI  - Hepatitis C virus and malignancy.
AB  - Hepatitis C virus (HCV) is a hepatotropic virus that causes chronic hepatitis,
      fibrosis and cirrhosis. HCV is associated with the development of primary liver
      tumors, namely hepatocellular carcinoma, cholangiocarcinoma and lymphoma. This
      article reviews HCV-related malignancies, and their prevalence and probable
      oncogenesis.

PMID- 17437525
TI  - Spatio-temporal profiling and degradation of alpha-amylase isozymes during barley
      seed germination.
AB  - Ten genes from two multigene families encode barley alpha-amylases. To gain
      insight into the occurrence and fate of individual isoforms during seed
      germination, the alpha-amylase repertoire was mapped by using a proteomics
      approach consisting of 2D gel electrophoresis, western blotting, and mass
      spectrometry. Mass spectrometric analysis confirmed that the 29 alpha-amylase
      positive 2D gel spots contained products of one (GenBank accession gi|113765) and
      two (gi|4699831 and gi|166985) genes encoding alpha-amylase 1 and 2,
      respectively, but lacked products from seven other genes. Eleven spots were
      identified only by immunostaining. Mass spectrometry identified 12 full-length
      forms and 12 fragments from the cultivar Barke. Products of both alpha-amylase 2
      entries co-migrated in five full-length and one fragment spot. The alpha-amylase
      abundance and the number of fragments increased during germination. Assessing the
      fragment minimum chain length by peptide mass fingerprinting suggested that alpha
      amylase 2 (gi|4699831) initially was cleaved just prior to domain B that
      protrudes from the (betaalpha)(8)-barrel between beta-strand 3 and alpha-helix 3,
      followed by cleavage on the C-terminal side of domain B and near the C-terminus.
      Only two shorter fragments were identified of the other alpha-amylase 2
      (gi|166985). The 2D gels of dissected tissues showed alpha-amylase degradation to
      be confined to endosperm. In contrast, the aleurone layer contained essentially
      only full-length alpha-amylase forms. While only products of the above three
      genes appeared by germination also of 15 other barley cultivars, the cultivars
      had distinct repertoires of charge and molecular mass variant forms. These
      patterns appeared not to be correlated with malt quality.

PMID- 17437527
TI  - An infectious and selectable full-length replicon system with hepatitis C virus
      JFH-1 strain.
AB  - AIM: The hepatitis C virus (HCV) strain JFH-1 was cloned from a patient with
      fulminant hepatitis. A JFH-1 subgenomic replicon and full-length JFH-1 RNA
      efficiently replicate in cultured cells. In this study, an infectious, selectable
      HCV replicon containing full-length JFH-1 cDNA was constructed. METHODS: The full
      genome replicon was constructed using the neomycin-resistant gene, EMCV IRES and
      wild-type JFH-1 cDNA. Huh7 cells were transfected with RNA synthesized in vitro,
      and then cultured with G418. Independent colonies were cloned to establish cell
      lines that replicate the full-length HCV replicon. RESULTS: HCV RNA replication
      was detected in each isolated cell line. HCV proteins and HCV RNA were secreted
      into culture medium, and exhibited identical density profiles. Interestingly,
      culture supernatants of the replicon cells were infectious for naive Huh7 cells.
      Long-term culture did not affect replication of replicon RNA in the replicon
      cells, but it reduced core protein secretion and infectivity of culture
      supernatant. Culture supernatant obtained after serial passage of replicon virus
      was infectious for Huh7 cells. CONCLUSIONS: Selectable infection was established
      using HCV replicon containing full-length genotype 2a JFH-1 cDNA. This system
      might be useful for HCV research.

PMID- 17437528
TI  - Identification of exocytotic membrane proteins, syntaxin-1 and SNAP-25, in
      Entamoeba histolytica from hamster liver.
AB  - Entamoeba histolytica is a protozoan parasite causing dysentery and in some cases
      liver abscesses. These effects have been attributed to cytolytic substances
      released by exocytosis. In this study, the presence of the proteins syntaxin-1
      and SNAP-25, which are assumed to be involved in exocytosis, were examined by
      immunohistochemistry, immunoelectron microscopy and western blot analysis.
      Syntaxin-1 and SNAP-25 were expressed in the vesicular, vacuolar and plasma
      membranes of E. histolytica trophozoites. It can be concluded that these proteins
      might be involved in exocytosis processes.

PMID- 17437529
TI  - Expression of vascular endothelial-cadherin in human hepatocellular carcinoma
      tissues.
AB  - AIM: Angiogenesis is important in tumor growth and progression to metastasis.
      Vascular endothelial (VE)-cadherin is an endothelial cell-specific cadherin
      required for angiogenesis, but its expression in hepatocellular carcinoma (HCC)
      tissues has not been examined. METHODS: Expression of VE-cadherin was analyzed in
      31 HCC frozen tissue specimens by immunohistochemical and immunoelectron
      microscopic procedures. In addition, the association of its expression with
      clinicopathological parameters was investigated to determine the possible
      diagnostic or predictive value of VE-cadherin expression in neoplastic and non
      neoplastic liver lesions. RESULTS: Immunoreactive VE-cadherin expression was
      faint or barely detectable on sinusoidal endothelial cells of normal liver but
      was evident on sinusoidal or capillary endothelium of chronic hepatitis,
      cirrhosis, and HCC tissues. VE-cadherin expression was more intense on capillary
      endothelium of HCC tissues in 26 (84%) of 31 patients than on sinusoidal
      endothelium of surrounding non-tumorous liver tissues with chronic liver
      diseases. The intensity or intracapillary extent of positive stain for VE
      cadherin on capillary endothelium of HCC tissues was significantly associated
      with tumor size, capsular invasion and tumor cell differentiation in HCC.
      CONCLUSIONS: Intense VE-cadherin expression was evident in capillary endothelium
      of HCC tissues, giving the first indication of association with
      clinicopathological features of HCC patients.

PMID- 17437530
TI  - Pathological analysis of oxyphilic granular hepatocytes and hepatocellular
      mitochondria in chronic hepatitis C.
AB  - AIM: Oxyphilic granular hepatocyte (OGH) results from hepatocellular changes
      associated with chronic hepatitis. The histopathological significance of OGH has
      not been clarified. METHODS: The subjects consisted of two groups of patients
      with hepatitis C: one group of patients who had undergone liver biopsy 3.8 times
      on average, and were followed for 8 years on average, and one group of
      hepatocellular carcinoma (HCC) patients who had undergone hepatectomy. The
      following items were examined: frequency of OGH, relationship between OGH and the
      degree of fibrosis and inflammation; amount of mitochondria in resected tissues;
      activity of mitochondrial enzymes; relationship between the development of HCC
      and OGH; and relationship between the duration of infection and OGH in the post
      transfusion patients. RESULTS: The incidence of OGH was 35.3% in liver biopsy
      patients and 46.9% in resected patients. A higher stage of fibrosis was
      associated with a higher frequency of OGH. Not only OGH but also hepatocyte
      mitochondria in the peripheral zone increased with the progression of fibrosis.
      Hepatocytes with or without increased mitochondria were randomly distributed. The
      mitochondrial enzyme activity was increased in hepatocytes with increased
      mitochondria. In the post-transfusion patients, a longer duration of infection
      and a higher stage of fibrosis were associated with a higher frequency of OGH. A
      high percentage of patients with OGH developed HCC. CONCLUSION: Mitochondrial
      changes are important histological findings related to the progression of liver
      lesions and the possible development of HCC.

PMID- 17437531
TI  - An early age-related increase in the frequency of CD4+ Foxp3+ cells in BDC2.5NOD
      mice.
AB  - The role of regulatory T cells (Treg) in maintaining tolerance to self has been
      intensively scrutinized, particularly since the discovery of Foxp3 as a Treg
      specific transcription factor. The BDC2.5NOD transgenic mouse is an excellent
      model of immunoregulation because it has a very low incidence of diabetes despite
      a highly autoreactive T-cell repertoire. It has previously been shown that
      reactivity against islets decreases with age in BDC2.5NOD mice. Here we show that
      there is a markedly higher frequency of Foxp3(+) Treg in the CD4(+) subset of 16
      20-week-old mice compared with 4- or 8-week-old mice. This phenomenon can be
      observed in the spleen, thymus, pancreatic draining lymph nodes and the pancreas
      itself. We show that this early age-related increase in the frequency of Foxp3(+)
      cells does not occur in wild-type NOD, BALB/c or C57BL/6 mice. Further, we show
      that, in contrast to some reports on Treg in wild-type NOD mice, the suppressive
      function of BDC2.5NOD Treg from 16- to 20-week-old mice is intact and comparable
      to that from 4- to 8-week-old mice both in vitro and in vivo. Our data offer
      insights into the long-term protection of BDC2.5NOD mice from diabetes and an
      explanation for the age-related decrease in anti-islet responses seen in
      BDC2.5NOD mice.

PMID- 17437532
TI  - A paracrine role for chemoattractant receptor-homologous molecule expressed on T
      helper type 2 cells (CRTH2) in mediating chemotactic activation of CRTH2+ CD4+ T
      helper type 2 lymphocytes.
AB  - Activation of human CRTH2(+) CD4(+) T helper type 2 (Th2) cells with anti
      CD3/anti-CD28 led to time-dependent production of prostaglandin D(2) (PGD(2))
      which peaked at 8 hr. The production of PGD(2) was completely inhibited by
      cotreatment with the cyclo-oxygenase inhibitor diclofenac (10 microm) but was not
      affected by cotreatment with ramatroban, a dual antagonist of both the
      thromboxane-like prostanoid (TP) receptor and the chemoattractant receptor
      homologous molecule expressed on Th2 cells (CRTH2). Supernatants from activated
      CRTH2(+) CD4(+) Th2 cells caused a concentration-dependent increase in the
      migration of naive CRTH2(+) CD4(+) Th2 cells compared to supernatants from
      unstimulated CRTH2(+) CD4(+) Th2 cells. The level of chemotactic activity peaked
      at 8 hr after activation, corresponding to the peak levels of PGD(2), but
      production of chemotactic activity was only partially inhibited by the cyclo
      oxygenase inhibitor diclofenac. In contrast, ramatroban completely inhibited the
      chemotactic responses of naive Th2 cells to supernatants from activated CRTH2(+)
      CD4(+) Th2 cells collected up to 8 hr after activation, although supernatants
      collected 24 hr after activation were less sensitive to inhibition by ramatroban.
      The selective TP antagonist SQ29548 did not inhibit migration of Th2 cells,
      implicating CRTH2 in this response. These data suggest that CRTH2 plays an
      important paracrine role in mediating chemotactic activation of Th2 cells.
      Interestingly, although PGD(2) is produced from Th2 cells and contributes to this
      paracrine activation, it appears that additional CRTH2 agonist factors are also
      produced by activated Th2 cells and the production of these factors occurs
      independently of the cyclo-oxygenase pathway of the arachidonic acid metabolism.

PMID- 17437533
TI  - BAC to immunology--bacterial artificial chromosome-mediated transgenesis for
      targeting of immune cells.
AB  - Thirty years after the first transgenic mouse was produced, a plethora of genetic
      tools has been developed to study immune cells in vivo. A powerful development is
      the bacterial artificial chromosome (BAC) transgenic approach, combining
      advantages of both conventional transgenic and knock-in gene-targeting
      strategies. In immunology the potential of BAC transgenic technology has yet to
      be fully harvested and, combined with a variety of elegant genetic tools, it will
      allow the analysis of complex immunological processes in vivo. In this short
      review, we discuss the applications of BACs in immunology, such as identification
      of regulatory regions, expression and cell-fate mapping, cell ablation,
      conditional mutations and the generation of humanized mice.

PMID- 17437535
TI  - Down-regulation of GRK2 after oxygen and glucose deprivation in rat hippocampal
      slices: role of the PI3-kinase pathway.
AB  - G protein-coupled receptor kinase 2 (GRK2) modulates G protein-coupled receptor
      desensitization and signaling. We previously described down-regulation of GRK2
      expression in vivo in rat neonatal brain following hypoxia-ischemia. In this
      study, we investigated the molecular mechanisms involved in GRK2 down-regulation,
      using organotypic cultures of neonatal rat hippocampal slices exposed to oxygen
      and glucose deprivation (OGD). We observed a 40% decrease in GRK2 expression 4 h
      post-OGD. No changes in GRK2 protein occurred after exposure of hippocampal
      slices to glucose deprivation only. No significant alterations in GRK2 mRNA
      expression were detected, suggesting a post-transcriptional effect of OGD on GRK2
      expression. Blockade of the proteasome pathway by MG132 prevented OGD-induced
      decrease of GRK2. It has been shown that extracellular signal-regulated kinase
      dependent phosphorylation of GRK2 at Ser670 triggers its turnover via the
      proteasome pathway. However, despite a significant increase of pSer670-GRK2 after
      OGD, inhibition of the extracellular signal-regulated kinase pathway by PD98059
      did neither prevent the hypoxia-ischemia-induced increase in pSer670-GRK2 nor the
      down-regulation of GRK2 protein. Interestingly, inhibition of phosphoinositide-3
      kinase with wortmannin inhibits both OGD-induced phosphorylation of GRK2 on
      Ser670 and the GRK2 decrease. In conclusion, OGD-induced phosphoinositide-3
      kinase-dependent phosphorylation of GRK2 on Ser670 is a novel mechanism leading
      to down-regulation of GRK2 protein via a proteasome-dependent pathway.

PMID- 17437534
TI  - CXCR6 is expressed on T cells in both T helper type 1 (Th1) inflammation and
      allergen-induced Th2 lung inflammation but is only a weak mediator of chemotaxis.
AB  - Numerous chemokine receptors are increased in number on T cells in inflamed
      tissues. Our objective was to examine CXCR6 expression on lymphocytes during
      immune and inflammatory reactions and its potential for mediating T-cell
      recruitment. The cDNA for rat CXCR6 was cloned and monoclonal antibodies (mAbs)
      to CXCR6 were developed. CXCR6 was present on 4-6% of CD4 and CD8 T cells in
      blood, normal lymph nodes (LNs) and the spleen, primarily on memory T cells. In
      vitro antigen re-stimulation of LN T cells from animals with autoimmune arthritis
      and experimental autoimmune encephalomyelitis (EAE) increased the proportion of
      CXCR6(+) T cells to 35-50% and anti-T-cell receptor (TCR) activation to 60-80%.
      In vivo, after antigen challenge of LNs there was only a small increase in
      CXCR6(+) T cells on the lymphoblasts in the LNs, and a much higher percentage of
      T cells were CXCR6(+) in virus-induced peritoneal exudates (approximately 47%)
      and in allergen-induced lung inflammation (33%). Chemotaxis of CXCR6-expressing
      inflammatory T cells to CXCL16 was poor, but that to CXCL10 was robust. We
      conclude that few T cells in normal and antigen-challenged LNs are CXCR6(+),
      whereas a high proportion of in vitro activated T cells and T cells from
      inflammatory sites are CXCR6(+), but these cells migrate poorly to CXCL16. This
      suggests that CXCR6 may contribute to T-cell positioning and activation, rather
      than recruitment. CXCR6 is also expressed on T cells not only in T helper type 1
      (Th1) inflammation (arthritis and EAE) but also, as shown here, in Th2
      inflammation, where it is increased after allergen challenge.

PMID- 17437536
TI  - Presenilin dependence of phospholipase C and protein kinase C signaling.
AB  - Presenilins (PSs) are involved in processing several proteins such as the amyloid
      precursor protein (APP), as well as in pathways for cell death and survival. We
      previously showed that some familial Alzheimer's disease PS mutations cause
      increased basal and acetylcholine muscarinic receptor-stimulated phospholipase C
      (PLC) activity which was gamma-secretase dependent. To further evaluate the
      dependence of PLC on PSs we measured PLC activity and the activation of variant
      protein kinase C (PKC) isoforms in mouse embryonic fibroblasts (MEFs) lacking
      either PS1, PS2, or both. PLC activity and PKCalpha and PKCgamma activations were
      significantly lower in PS1 and PS2 double knockout MEFs after PLC stimulation.
      Protein levels of PKCalpha and PKCgamma were lower in PS1 and PS2 double knockout
      MEFs. In contrast, PKCdelta levels were significantly elevated in PS1 and PS2
      double knockout as well as in PS1 knockout MEFs. Also, PKCdelta levels were
      lowered after transfection of PS1 into PS1 knockout or PS double knockout MEFs.
      Using APP knockout MEFs we showed that the expression of PKCalpha, but not the
      other PKC isoforms is partially dependent on APP and can be regulated by APP
      intracellular domain (AICD). These results show that PLC and PKC activations are
      modulated by PS and also that PSs differentially regulate the expression of PKC
      isoforms by both APP/AICD-dependent and independent mechanisms.

PMID- 17437537
TI  - Sphingolipids are necessary for nicotinic acetylcholine receptor export in the
      early secretory pathway.
AB  - The nicotinic acetylcholine receptor (AChR) is the prototype ligand-gated ion
      channel, and its function is dependent on its lipid environment. In order to
      study the involvement of sphingolipids (SL) in AChR trafficking, we used
      pharmacological approaches to dissect the SL biosynthetic pathway in CHO-K1/A5
      cells heterologously expressing the muscle-type AChR. When SL biosynthesis was
      impaired, the cell surface targeting of AChR diminished with a concomitant
      increase in the intracellular receptor pool. The SL-inhibiting drugs increased
      unassembled AChR forms, which were retained at the endoplasmic reticulum (ER).
      These effects on AChR biogenesis and trafficking could be reversed by the
      addition of exogenous SL, such as sphingomyelin. On the basis of these effects we
      propose a 'chaperone-like' SL intervention at early stages of the AChR
      biosynthetic pathway, affecting both the efficiency of the assembly process and
      subsequent receptor trafficking to the cell surface.

PMID- 17437539
TI  - A cell-biological model of p75NTR signaling.
AB  - Neurotrophin stimulation of tropomyosin-related kinase (Trk) and p75 receptors
      influences cellular processes such as proliferation, growth, differentiation, and
      other cell-specific functions, as well as regeneration. In contrast to Trk
      receptors, which have a well-defined trophic role, p75 has activities ranging
      from trophism to apoptosis. Continued neurotrophin stimulation of differentiating
      neurons transforms the initially trophic character of p75 signaling into negative
      growth control and overstimulation leads to apoptosis. This function shift
      reflects the signaling effects of ceramide that is generated upon stimulation of
      p75. The use of ceramide signaling by p75 may provide a key to understanding the
      cell-biological role of p75. The review presents arguments that the control of
      cell shape formation and cell selection can serve as an organizing principle of
      p75 signaling. Concurrent stimulation by neurotrophins of p75 and Trk receptors
      constitutes a dual growth control with antagonistic and synergistic elements
      aimed at optimal morphological and functional integration of cells and cell
      populations into their context.

PMID- 17437538
TI  - Brain energy metabolism and neurotransmission at near-freezing temperatures: in
      vivo (1)H MRS study of a hibernating mammal.
AB  - The brain of a hibernating mammal withstands physiological extremes that would
      result in cerebral damage and death in a non-hibernating species such as humans.
      To examine the possibility that this neuroprotection results from alterations in
      cerebral metabolism, we used in vivo(1)H NMR spectroscopy at high field (9.4 T)
      to measure the concentration of 18 metabolites (neurochemical profile) in the
      brain of 13-lined ground squirrels (Spermophilus tridecemlineatus) before,
      during, and after hibernation. Resolved in vivo(1)H NMR spectra were obtained
      even at low temperature in torpid hibernators ( approximately 7 degrees C). The
      phosphocreatine-to-creatine ratio was increased during torpor (+143%) indicating
      energy storage, and remained increased to a lesser extent during interbout
      arousal (IBA) (+83%). The total gamma-aminobutyric acid concentration was
      increased during torpor (+135%) and quickly returned to baseline during IBA.
      Glutamine (Gln) was decreased (-54%) during torpor but quickly returned to normal
      levels during IBA and after terminal arousal in the spring. Glutamate (Glu) was
      also decreased during torpor (-17%), but remained decreased during IBA (-20%
      compared with fall), and returned to normal level in the spring. Our observation
      that Glu and Gln levels are depressed in the brain of hibernators suggests that
      the balance between anaplerosis and loss of Glu and Gln (because of glutamatergic
      neurotransmission or other mechanisms) is altered in hibernation.

PMID- 17437540
TI  - Nidogen is a prosurvival and promigratory factor for adult Schwann cells.
AB  - Schwann cells provide a favorable microenvironment for successful regeneration of
      the injured peripheral nerve. Even though the roles of extracellular matrix
      proteins in the Schwann cell physiology have long been studied, the precise
      function of nidogen, a ubiquitous component of the basal lamina, in Schwann cells
      is unknown. In this study, we show that the protein and mRNA messages for
      nidogens are up-regulated in the sciatic nerve after sciatic nerve transection.
      We demonstrate that recombinant nidogen-1 increased the process formation of
      Schwann cells cultured from adult rat sciatic nerves and that nidogen-1 prevented
      Schwann cells from serum-deprivation-induced death. In addition, nidogen-1
      promoted spontaneous migration of Schwann cells in two-independent migration
      assays. The Schwann cell responses to the recombinant nidogen-1 were specific
      because the nidogen-binding ectodomain of tumor endothelial marker 7 inhibited
      the nidogen responses without affecting Schwann cell response to laminin.
      Finally, we found that beta1 subunit-containing integrins play a key role in the
      nidogen-induced process formation, survival, and migration of Schwann cells.
      Altogether, these results indicate that nidogen has a prosurvival and
      promigratory activity on Schwann cells in the peripheral nerve.

PMID- 17437541
TI  - Syndapin I and endophilin I bind overlapping proline-rich regions of dynamin I:
      role in synaptic vesicle endocytosis.
AB  - Dynamin I mediates vesicle fission during synaptic vesicle endocytosis (SVE). Its
      proline-rich domain (PRD) binds the Src-homology 3 (SH3) domain of a subset of
      proteins that can deform membranes. Syndapin I, amphiphysin I, and endophilin I
      are its major partners implicated in SVE. Syndapin binding is controlled by
      phosphorylation at Ser-774 and Ser-778 in the dynamin phospho-box. We now define
      syndapin and endophilin-binding sites by peptide competition and site-directed
      mutagenesis. Both bound the same region of the dynamin PRD and both exhibited
      unusual bidirectional binding modes around core PxxP motifs, unlike amphiphysin
      which employed a class II binding mode. Endophilin binds to tandem PxxP motifs in
      the sequence (778)SPTPQRRAPAVPPARPGSR(796) in dynamin, with SPTPQ being an
      overhang sequence. In contrast, syndapin binding involves two components in the
      region (772)RRSPTSSPTPQRRAPAVPPARPGSR(796). It required a single PxxP core and a
      non-PxxP N-terminally anchored extension which bridges the phospho-box and may
      contribute to binding specificity and affinity. Syndapin binding is exquisitely
      sensitive to the introduction of negative charges almost anywhere along this
      region, explaining why it is a highly tuned phospho-sensor. Over-expression of
      dynamin point mutants that fail to bind syndapin or endophilin inhibit SVE in
      cultured neurons. Due to overlapping binding sites the interactions between
      dynamin and syndapin or endophilin were mutually exclusive. Because syndapin acts
      as a phospho-sensor, this supports its role in depolarization-induced SVE at the
      synapse, which involves dynamin dephosphorylation. We propose syndapin and
      endophilin function either at different stages during SVE or in mechanistically
      distinct types of SVE.

PMID- 17437542
TI  - Lysophosphatidylcholine potentiates Ca2+ influx, pore formation and p44/42 MAP
      kinase phosphorylation mediated by P2X7 receptor activation in mouse microglial
      cells.
AB  - The P2X7 receptor (P2X7R) is an ATP-gated ion channel highly expressed in
      microglia. P2X7R plays important roles in inflammatory responses in the brain.
      However, little is known about the mechanisms regulating its functions in
      microglia. Lysophosphatidylcholine (LPC), an inflammatory phospholipid that
      promotes microglial activation, may have some relevance to P2X7R signaling in
      terms of microglial function. In this study, we examined its effects on P2X7R
      signaling in a mouse microglial cell line (MG6) and primary microglia. LPC
      facilitated the sustained increase in the intracellular Ca(2+) concentration
      ([Ca(2+)](i)) through P2X7R channels activated by ATP or BzATP. The potentiated
      increase in [Ca(2+)](i) was actually inhibited by P2X7R antagonists, brilliant
      blue G and oxidized ATP. The potentiating effect of LPC was not observed with P2Y
      receptor systems, which are also expressed in MG6 cells. G2A, a receptor for LPC,
      was expressed in MG6 cells, but not involved in the facilitating effect of LPC on
      the P2X7R-mediated change in [Ca(2+)](i). Furthermore, LPC enhanced the P2X7R
      associated formation of membrane pores and the activation of p44/42 mitogen
      activated protein kinase. These results suggest that LPC may regulate microglial
      functions in the brain by enhancing the sensitivity of P2X7R.

PMID- 17437543
TI  - Blood-brain barrier disruption induces in vivo degeneration of nigral
      dopaminergic neurons.
AB  - We have evaluated the possibility that changes in the vascular system may
      constitute a contributing factor for the death of nigral dopaminergic neurons in
      Parkinson's disease. Thus, we have employed intranigral injections of vascular
      endothelial growth factor (VEGF), the most potent inducer of blood-brain barrier
      (BBB) permeability. A single dose of 1 mug of VEGF, chosen from a dose-response
      study, highly disrupted the BBB in the ventral mesencephalon in a time-dependent
      manner. A strong regional correlation between BBB disruption and loss of tyrosine
      hydroxylase-positive neurons was evident. Moreover, Fluoro-Jade B labelling
      showed the presence of dying neurons in the substantia nigra in response to VEGF
      injection. High number of TUNEL-positive nuclei was observed in this area along
      with activation of caspase 3 within nigral dopaminergic neurons. Analysis of the
      glial population demonstrated a strong inflammatory response and activation of
      astroglia in response to BBB disruption. We conclude that disruption of the BBB
      may be a causative factor for degeneration of nigral dopaminergic neurons.

PMID- 17437544
TI  - Transcriptome analysis reveals altered cholesterol metabolism during the
      neurodegeneration in mouse scrapie model.
AB  - To identify the dynamic transcriptional alterations in CNS during the development
      of prion disease, brains of scrapie-infected mice and age-matched, mock
      inoculated controls were analyzed immediately before inoculation and at different
      time points post-inoculation using Affymetrix microarray technique. A total of
      449 probe sets, representing 430 genes, showed differential expression between
      scrapie- and mock-inoculated mice over the time course. These genes could be
      separated into two clusters according to expression patterns: the genes in
      cluster 1 demonstrated lower mRNA levels in scrapie-infected brains when compared
      with mock-inoculated brains, whereas genes in cluster 2 showed higher mRNA levels
      in scrapie-infected brains. Functional analysis of differentially expressed genes
      revealed the most severely affected biological process: cholesterol metabolism.
      The expression patterns of the cholesterol-related genes indicated an inhibited
      cholesterol synthesis in the diseased brains. Conspicuously, a number of cluster
      1 genes, including some of cholesterol-related genes, showed not only decreasing
      mRNA levels in scrapie-infected brains but also increasing mRNA levels in mock
      inoculated brains with increasing age. Quantitative RT-PCR analysis of some
      cholesterol-related genes in untreated mice suggested that changes of the
      examined genes observed in mock-inoculated brains are mainly age related. This
      finding indicated a link between age-related genes and scrapie-associated
      neurodegeneration.

PMID- 17437545
TI  - Delayed treatment with cannabidiol has a cerebroprotective action via a
      cannabinoid receptor-independent myeloperoxidase-inhibiting mechanism.
AB  - We examined the neuroprotective mechanism of cannabidiol, non-psychoactive
      component of marijuana, on the infarction in a 4 h mouse middle cerebral artery
      (MCA) occlusion model in comparison with Delta(9)-tetrahydrocannabinol (Delta(9)
      THC). Release of glutamate in the cortex was measured at 2 h after MCA occlusion.
      Myeloperoxidase (MPO) and cerebral blood flow were measured at 1 h after
      reperfusion. In addition, infarct size and MPO were determined at 24 and 72 h
      after MCA occlusion. The neuroprotective effect of cannabidiol was not inhibited
      by either SR141716 or AM630. Both pre- and post-ischemic treatment with
      cannabidiol resulted in potent and long-lasting neuroprotection, whereas only pre
      ischemic treatment with Delta(9)-THC reduced the infarction. Unlike Delta(9)-THC,
      cannabidiol did not affect the excess release of glutamate in the cortex after
      occlusion. Cannabidiol suppressed the decrease in cerebral blood flow by the
      failure of cerebral microcirculation after reperfusion and inhibited MPO activity
      in neutrophils. Furthermore, the number of MPO-immunopositive cells was reduced
      in the ipsilateral hemisphere in cannabidiol-treated group. Cannabidiol provides
      potent and long-lasting neuroprotection through an anti-inflammatory CB(1)
      receptor-independent mechanism, suggesting that cannabidiol will have a
      palliative action and open new therapeutic possibilities for treating
      cerebrovascular disorders.

PMID- 17437547
TI  - Involvement of KCNQ2 subunits in [3H]dopamine release triggered by depolarization
      and pre-synaptic muscarinic receptor activation from rat striatal synaptosomes.
AB  - KCNQ2 and KCNQ3 subunits encode for the muscarinic-regulated current (I(KM)), a
      sub-threshold voltage-dependent K+ current regulating neuronal excitability. In
      this study, we have investigated the involvement of I(KM) in dopamine (DA)
      release from rat striatal synaptosomes evoked by elevated extracellular K+
      concentrations ([K+]e) and by muscarinic receptor activation. [3H]dopamine
      ([3H]DA) release triggered by 9 mmol/L [K+]e was inhibited by the I(KM) activator
      retigabine (0.01-30 micromol/L; Emax = 54.80 +/- 3.85%; IC50 = 0.50 +/- 0.36
      micromol/L). The I(KM) blockers tetraethylammonium (0.1-3 mmol/L) and XE-991 (0.1
      30 micromol/L) enhanced K+-evoked [3H]DA release and prevented retigabine-induced
      inhibition of depolarization-evoked [3H]DA release. Retigabine-induced inhibition
      of K+-evoked [3H]DA release was also abolished by synaptosomal entrapment of
      blocking anti-KCNQ2 polyclonal antibodies, an effect prevented by antibody pre
      absorption with the KCNQ2 immunizing peptide. Furthermore, the cholinergic
      agonist oxotremorine (OXO) (1-300 micromol/L) potentiated 9 mmol/L [K+]e-evoked
      [3H]DA release (Emax = 155 +/- 9.50%; EC50 = 25 +/- 1.80 micromol/L). OXO (100
      micromol/L)-induced [3H]DA release enhancement was competitively inhibited by
      pirenzepine (1-10 nmol/L) and abolished by the M3-preferring antagonist 4
      diphenylacetoxy N-methylpiperidine methiodide (1 micromol/L), but was unaffected
      by the M1-selective antagonist MT-7 (10-100 nmol/L) or by Pertussis toxin (1.5-3
      microg/mL), which uncouples M2- and M4-mediated responses. Finally, OXO-induced
      potentiation of depolarization-induced [3H]DA release was not additive to that
      produced by XE-991 (10 micromol/L), was unaffected by retigabine (10 micromol/L),
      and was abolished by synaptosomal entrapment of anti-KCNQ2 antibodies.
      Collectively, these findings indicate that, in rat striatal nerve endings, I(KM)
      channels containing KCNQ2 subunits regulate depolarization-induced DA release and
      that I(KM) suppression is involved in the reinforcement of depolarization-induced
      DA release triggered by the activation of pre-synaptic muscarinic
      heteroreceptors.

PMID- 17437546
TI  - Excitotoxicity-related endocytosis in cortical neurons.
AB  - Recent studies showed that endocytosis is enhanced in neurons exposed to an
      excitototoxic stimulus. We here confirm and analyze this new phenomenon using
      dissociated cortical neuronal cultures. NMDA-induced uptake (FITC-dextran or FITC
      or horseradish peroxidase) occurs in these cultures and is due to endocytosis,
      not to cell entry through damaged membranes; it requires an excitotoxic dose of
      NMDA and is dependent on extracellular calcium, but occurs early, while the
      neuron is still intact and viable. It involves two components, NMDA-induced and
      constitutive, with different characteristics. Neither component involves specific
      binding of the endocytosed molecules to a saturable receptor. Strikingly,
      molecules internalized by the NMDA-induced component are targeted to neuronal
      nuclei. This component, but not the constitutive one, is blocked by a c-Jun N
      terminal protein kinase inhibitor. In conclusion, an excitotoxic dose of NMDA
      triggers c-Jun N-terminal protein kinase-dependent endocytosis in cortical
      neuronal cultures, providing an in vitro model of the excitotoxicity-induced
      endocytosis reported in intact tissues.

PMID- 17437548
TI  - Nicotine induces tyrosine hydroxylase plasticity in the neurodegenerating
      striatum.
AB  - It has been shown that nicotine prevents the loss of dopamine (DA) in the corpus
      striatum (CS) after 6-hydroxydopamine injection in the substantia nigra. To study
      the role of the enzyme tyrosine hydroxylase (TH; EC 1.14.16.2) in this
      experimental paradigm, we have examined its activity by assessing the
      accumulation of l-3,4-dihydroxyphenylalanine after inhibiting the subsequent
      enzyme in the DA synthetic pathway, aromatic l-amino acid decarboxylase, with 3
      hydroxybenzylhydrazine. In addition the amount of TH protein was assessed by
      western blotting and its distribution in the CS was examined using
      immunohistochemical methods. 6-hydroxydopamine injection produced a significant
      decrease in DA levels and l-3,4-dihydroxyphenylalanine accumulation, as well as
      decreases in TH protein and TH immunoreactive fibres in the CS. After nicotine
      treatment, the decrease in TH protein in the CS was significantly reduced, with a
      concomitant preservation of TH activity, but nicotine did not alter the number of
      TH immunoreactive fibres. The activity and amount of TH did not change in the
      contralateral (intact) CS. Thus, nicotine induces long lasting TH plasticity in
      the degenerating CS. A synergistic action of nicotine-activated and lesion
      originated signals appears necessary for the expression of this neuronal
      molecular plasticity.

PMID- 17437549
TI  - Mitogen-activated protein kinase phosphatase-1 (MKP-1) preferentially
      dephosphorylates p42/44MAPK but not p38MAPK in rat pinealocytes.
AB  - We recently reported a diurnal and norepinephrine (NE) -induced expression of
      mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in the rat pineal
      gland and postulated that this MKP-1 expression might impact adrenergic-regulated
      arylalkylamine-N-acetyltransferase (AA-NAT) activity via modulation of MAPKs. In
      this study, we investigated the effect of depletion of MKP-1 expression by using
      doxorubicin, a topoisomerase inhibitor that suppresses the expression of MKP-1 in
      other cell types and small interfering RNA targeted against Mkp1 in NE-stimulated
      pinealocytes. We found that both treatments were effective in inhibiting NE
      induction of MKP-1 expression. Moreover, both treatments also resulted in a
      prolonged activation of p42/44MAPK and an increase in AA-NAT induction by NE. In
      contrast, treatment of pinealocytes with PD98059, an inhibitor of MAPK kinase,
      reduced NE-stimulated AA-NAT activity. Interestingly, suppressing MKP-1
      expression had no effect on the time profile of NE-stimulated p38MAPK activation.
      These results indicate that MKP-1 modulates the profile of AA-NAT activity by
      selectively shaping the activation profile of p42/44MAPK but not that of p38MAPK.

PMID- 17437550
TI  - Caffeic acid phenethyl ester reduces neurovascular inflammation and protects rat
      brain following transient focal cerebral ischemia.
AB  - Ischemic stroke is a neurovascular disease treatable by thrombolytic therapy, but
      the therapy has to be initiated within 3 h of the incident. This therapeutic
      limitation stems from the secondary injury which results mainly from oxidative
      stress and inflammation. A potent antioxidant/anti-inflammatory agent, caffeic
      acid phenethyl ester (CAPE) has potential to mitigate stroke's secondary injury,
      and thereby widening the therapeutic window. We observed that CAPE protected the
      brain in a dose-dependent manner (1-10 mg/kg body weight) and showed a wide
      therapeutic window (about 18 h) in a rat model of transient focal cerebral
      ischemia and reperfusion. The treatment also increased nitric oxide and
      glutathione levels, decreased lipid peroxidation and nitrotyrosine levels, and
      enhanced cerebral blood flow. CAPE down-regulated inflammation by blocking
      nuclear factor kappa B activity. The affected mediators included adhesion
      molecules (intercellular adhesion molecule-1 and E-selectin), cytokines (tumor
      necrosis factor-alpha and interleukin-1beta) and inducible nitric oxide synthase.
      Anti-inflammatory action of CAPE was further documented through reduction of ED1
      (marker of activated macrophage/microglia) expression. The treatment inhibited
      apoptotic cell death by down-regulating caspase 3 and up-regulating anti
      apoptotic protein Bcl-xL. Conclusively, CAPE is a promising drug candidate for
      ischemic stroke treatment due to its inhibition of oxidative stress and
      inflammation, and its clinically relevant wide therapeutic window.

PMID- 17437552
TI  - 'Mild Uncoupling' does not decrease mitochondrial superoxide levels in cultured
      cerebellar granule neurons but decreases spare respiratory capacity and increases
      toxicity to glutamate and oxidative stress.
AB  - Cultured rat cerebellar granule neurons were incubated with low nanomolar
      concentrations of the protonophore carbonylcyanide-p-trifluoromethoxyphenyl
      hydrazone (FCCP) to test the hypothesis that 'mild uncoupling' could be
      neuroprotective by decreasing oxidative stress. To quantify the uncoupling,
      respiration and mitochondrial membrane potential (Deltapsi(m)) were determined in
      parallel as a function of FCCP concentration. Deltapsi(m) dropped by less than 10
      mV before respiratory control was lost. Conditions for the valid estimation of
      matrix superoxide levels were determined from the rate of oxidation of the matrix
      targeted fluorescent probe MitoSOX. No significant change in the level of matrix
      superoxide could be detected on addition of FCCP while respiratory control was
      retained, although cytoplasmic superoxide levels measured by dihydroethidium
      oxidation increased. 'Mild uncoupling' by 30 nmol/L FCCP did not alleviate
      neuronal dysregulation induced by glutathione depletion and significantly
      enhanced that due to menadione-induced oxidative stress. Low protonophore
      concentrations enhanced N-methyl-d-aspartate receptor-induced delayed calcium
      deregulation consistent with a decrease in the spare respiratory capacity
      available to match the bioenergetic demand of chronic receptor activation. It is
      concluded that the 'mild uncoupling' hypothesis is not supported by this model.

PMID- 17437551
TI  - Identification, physiological actions, and distribution of TPSGFLGMRamide: a
      novel tachykinin-related peptide from the midgut and stomatogastric nervous
      system of Cancer crabs.
AB  - In most invertebrates, multiple species-specific isoforms of tachykinin-related
      peptide (TRP) are common. In contrast, only a single conserved TRP isoform,
      APSGFLGMRamide, has been documented in decapod crustaceans, leading to the
      hypothesis that it is the sole TRP present in this arthropod order. Previous
      studies of crustacean TRPs have focused on neuronal tissue, but the recent
      demonstration of TRPs in midgut epithelial cells in Cancer species led us to
      question whether other TRPs are present in the gut, as is the case in insects.
      Using direct tissue matrix assisted laser desorption/ionization Fourier transform
      mass spectrometry, in combination with sustained off-resonance irradiation
      collision-induced dissociation, we found that at least one additional TRP is
      present in Cancer irroratus, Cancer borealis, Cancer magister, and Cancer
      productus. The novel TRP isoform, TPSGFLGMRamide, was present not only in the
      midgut, but also in the stomatogastric nervous system (STNS). In addition, we
      identified an unprocessed TRP precursor APSGFLGMRG, which was detected in midgut
      tissues only. TRP immunohistochemistry, in combination with preadsorption
      studies, suggests that APSGFLGMRamide and TPSGFLGMRamide are co-localized in the
      stomatogastric ganglion (STG), which is contained within the STNS. Exogenous
      application of TPSGFLGMRamide to the STG elicited a pyloric motor pattern that
      was identical to that elicited by APSGFLGMRamide, whereas APSGFLGMRG did not
      alter the pyloric motor pattern.

PMID- 17437553
TI  - Estimating heart rate and RSA from the mattress-recorded kinetocardiogram.
AB  - This article describes a method for extracting heart rate (HR) and respiratory
      sinus arrhythmia (RSA) from the kinetocardiogram (KCG) recorded from
      accelerometers embedded in a mattress topper. Validation has been performed via
      comparison with simultaneously recorded ECG. All-night estimates of HR and RSA
      magnitude derived from both methods were highly correlated. KCG-derived estimates
      of HR were slightly lower, and those of RSA magnitude higher, than those derived
      from ECG. These biases are consistent with the need to constrain KCG estimation
      to periods free of body movement. Mattress actigraphy represents a zero-burden
      method of obtaining intensive longitudinal indices of cardiac status.

PMID- 17437554
TI  - Range of sensory gating values and test-retest reliability in normal subjects.
AB  - This article characterizes gating in normal subjects using P50, N100, and P200
      components in a paired-click paradigm and compares the test-retest reliabilities
      of the three components. Sixty-seven normal subjects had gating data from a
      standard paired-click paradigm; 30 had test-retest data. The test-retest
      reliability of the amplitudes, latencies, and sensory gating indices derived from
      the P50, N100, and P200 responses were compared. Measured gating ratios showed
      either normal or positively skewed distributions. Test-retest reliability of the
      P50 gating ratio did not reach significance, but N100 and P200 ratios showed
      better reliability (.50 and .64). The P50 difference score was more reliable
      (.61), and the N100 and P200 test-retest reliabilities of difference scores were
      high (.83 and .81, respectively). N100 and P200 attenuation is reliable; further
      work is needed to develop more reliable P50 gating measures.

PMID- 17437555
TI  - Predictive information and error processing: the role of medial-frontal cortex
      during motor control.
AB  - We have recently provided evidence that an error-related negativity (ERN), an ERP
      component generated within medial-frontal cortex, is elicited by errors made
      during the performance of a continuous tracking task (O.E. Krigolson & C.B.
      Holroyd, 2006). In the present study we conducted two experiments to investigate
      the ability of the medial-frontal error system to evaluate predictive error
      information. In two experiments participants used a joystick to perform a
      computer-based continuous tracking task in which some tracking errors were
      inevitable. In both experiments, half of these errors were preceded by a
      predictive cue. The results of both experiments indicated that an ERN-like
      waveform was elicited by tracking errors. Furthermore, in both experiments the
      predicted error waveforms had an earlier peak latency than the unpredicted error
      waveforms. These results demonstrate that the medial-frontal error system can
      evaluate predictive error information.

PMID- 17437556
TI  - Does the error negativity reflect response conflict strength? Evidence from a
      Simon task.
AB  - The error (-related) negativity (Ne or ERN) has been related to detecting the
      mismatch between incorrectly executed and appropriate responses or,
      alternatively, to the degree of conflict between different response alternatives.
      In this study different levels of response conflict were generated by
      manipulating task difficulty in a Simon task. According to the product of
      incorrect and subsequent correct EMG activation, the amount of conflict in error
      trials was indeed larger for the easy than for the hard condition. In contrast,
      Ne/ERN amplitudes did not differ between difficulty conditions, nor was the
      amount of conflict mirrored by Ne/ERN amplitude. Therefore, the present data are
      at variance with the hypothesis that the Ne/ERN reflects the degree of response
      conflict.

PMID- 17437557
TI  - A critical review of adaptive genetic variation in Atlantic salmon: implications
      for conservation.
AB  - Here we critically review the scale and extent of adaptive genetic variation in
      Atlantic salmon (Salmo salar L.), an important model system in evolutionary and
      conservation biology that provides fundamental insights into population
      persistence, adaptive response and the effects of anthropogenic change. We
      consider the process of adaptation as the end product of natural selection, one
      that can best be viewed as the degree of matching between phenotype and
      environment. We recognise three potential sources of adaptive variation:
      heritable variation in phenotypic traits related to fitness, variation at the
      molecular level in genes influenced by selection, and variation in the way genes
      interact with the environment to produce phenotypes of varying plasticity. Of all
      phenotypic traits examined, variation in body size (or in correlated characters
      such as growth rates, age of seaward migration or age at sexual maturity)
      generally shows the highest heritability, as well as a strong effect on fitness.
      Thus, body size in Atlantic salmon tends to be positively correlated with
      freshwater and marine survival, as well as with fecundity, egg size, reproductive
      success, and offspring survival. By contrast, the fitness implications of
      variation in behavioural traits such as aggression, sheltering behaviour, or
      timing of migration are largely unknown. The adaptive significance of molecular
      variation in salmonids is also scant and largely circumstantial, despite
      extensive molecular screening on these species. Adaptive variation can result in
      local adaptations (LA) when, among other necessary conditions, populations live
      in patchy environments, exchange few or no migrants, and are subjected to
      differential selective pressures. Evidence for LA in Atlantic salmon is indirect
      and comes mostly from ecological correlates in fitness-related traits, the
      failure of many translocations, the poor performance of domesticated stocks,
      results of a few common-garden experiments (where different populations were
      raised in a common environment in an attempt to dissociate heritable from
      environmentally induced phenotypic variation), and the pattern of inherited
      resistance to some parasites and diseases. Genotype x environment interactions
      occurr for many fitness traits, suggesting that LA might be important. However,
      the scale and extent of adaptive variation remains poorly understood and probably
      varies, depending on habitat heterogeneity, environmental stability and the
      relative roles of selection and drift. As maladaptation often results from
      phenotype-environment mismatch, we argue that acting as if populations are not
      locally adapted carries a much greater risk of mismanagement than acting under
      the assumption for local adaptations when there are none. As such, an
      evolutionary approach to salmon conservation is required, aimed at maintaining
      the conditions necessary for natural selection to operate most efficiently and
      unhindered. This may require minimising alterations to native genotypes and
      habitats to which populations have likely become adapted, but also allowing for
      population size to reach or extend beyond carrying capacity to encourage
      competition and other sources of natural mortality.

PMID- 17437558
TI  - Petroleum hydrocarbon contamination in boreal forest soils: a mycorrhizal
      ecosystems perspective.
AB  - The importance of developing multi-disciplinary approaches to solving problems
      relating to anthropogenic pollution is now clearly appreciated by the scientific
      community, and this is especially evident in boreal ecosystems exposed to
      escalating threats of petroleum hydrocarbon (PHC) contamination through expanded
      natural resource extraction activities. This review aims to synthesize
      information regarding the fate and behaviour of PHCs in boreal forest soils in
      both ecological and sustainable management contexts. From this, we hope to
      evaluate potential management strategies, identify gaps in knowledge and guide
      future research. Our central premise is that mycorrhizal systems, the ubiquitous
      root symbiotic fungi and associated food-web communities, occupy the structural
      and functional interface between decomposition and primary production in northern
      forest ecosystems (i.e. underpin survival and productivity of the ecosystem as a
      whole), and, as such, are an appropriate focal point for such a synthesis. We
      provide pertinent basic information about mycorrhizas, followed by insights into
      the ecology of ecto- and ericoid mycorrhizal systems. Next, we review the fate
      and behaviour of PHCs in forest soils, with an emphasis on interactions with
      mycorrhizal fungi and associated bacteria. Finally, we summarize implications for
      ecosystem management. Although we have gained tremendous insights into
      understanding linkages between ecosystem functions and the various aspects of
      mycorrhizal diversity, very little is known regarding rhizosphere communities in
      PHC-contaminated soils. This makes it difficult to translate ecological knowledge
      into environmental management strategies. Further research is required to
      determine which fungal symbionts are likely to survive and compete in various
      ecosystems, whether certain fungal - plant associations gain in ecological
      importance following contamination events, and how PHC contamination may
      interfere with processes of nutrient acquisition and exchange and metabolic
      processes. Research is also needed to assess whether the metabolic capacity for
      intrinsic decomposition exists in these ecosystems, taking into account
      ecological variables such as presence of other organisms (and their involvement
      in syntrophic biodegradation), bioavailability and toxicity of mixtures of PHCs,
      and physical changes to the soil environment.

PMID- 17437559
TI  - Ecological correlates of body size in relation to cell size and cell number:
      patterns in flies, fish, fruits and foliage.
AB  - Body size is important to most aspects of biology and is also one of the most
      labile traits. Despite its importance we know remarkably little about the
      proximate (developmental) factors that determine body size under different
      circumstances. Here, I review what is known about how cell size and number
      contribute to phenetic and genetic variation in body size in Drosophila
      melanogaster, several fish, and fruits and leaves of some angiosperms. Variation
      in resources influences size primarily through changes in cell number while
      temperature acts through cell size. The difference in cellular mechanism may also
      explain the differences in growth trajectories resulting from food and
      temperature manipulations. There is, however, a poorly recognized interaction
      between food and temperature effects that needs further study. In addition, flies
      show a sexual dimorphism in temperature effects with the larger sex responding by
      changes in cell size and the smaller sex showing changes in both cell size and
      number. Leaf size is more variable than other organs, but there appears to be a
      consistent difference between how shade-tolerant and shade-intolerant species
      respond to light level. The former have larger leaves via cell size under shade,
      the latter via cell number in light conditions. Genetic differences, primarily
      from comparisons of D. melanogaster, show similar variation. Direct selection on
      body size alters cell number only, while temperature selection results in
      increased cell size and decreased cell number. Population comparisons along
      latitudinal clines show that larger flies have both larger cells and more cells.
      Use of these proximate patterns can give clues as to how selection acts in the
      wild. For example, the latitudinal pattern in D. melanogaster is usually assumed
      to be due to temperature, but the cellular pattern does not match that seen in
      laboratory selection at different temperatures.

PMID- 17437560
TI  - Parasite recruitment and oceanographic regime: evidence suggesting a relationship
      on a global scale.
AB  - We here investigate the relationship between oceanographic processes and
      variability in parasite recruitment to host populations using existing data from
      host-parasite systems encountering differing hydrographic conditions. Combined
      epidemiological data obtained from both exploited fish and cephalopod populations
      indicate that variability in recruitment of parasite infracommunities tends to be
      associated with major current systems of the World's oceans. It appears that
      instability in water masses caused by physical perturbations (e.g. water mass
      convergence and turbulent mixing in upwelling systems) is associated with
      instability of trophic interactions over time, which in turn leads to a paucity
      of parasite communities in that area. The likely relationship between parasite
      recruitment and oceanographic regime should be extremely useful to the fishing
      industry and also as an indicator of ecosystem health.

PMID- 17437561
TI  - The role of chemical communication in mate choice.
AB  - Chemical signals are omnipresent in sexual communication in the vast majority of
      living organisms. The traditional paradigm was that their main purpose in sexual
      behaviour was to coordinate mate and species recognition and thus pheromones were
      conserved in structure and function. In recent years, this view has been
      challenged by theoretical analyses on the evolution of pheromones and empirical
      reports of mate choice based on chemical signals. The ability to measure
      precisely the quantity and quality of chemicals emitted by single individuals has
      also revealed considerable individual variation in chemical composition and
      release rates, and there is mounting evidence that prospecting mates respond to
      this variation. Here, we review the evidence for pheromones as indicators of mate
      quality and examine the extent of their use in individual mate assessment. We
      begin by briefly defining the levels of mate choice--species recognition, mate
      recognition and mate assessment. We then explore the degree to which pheromones
      satisfy the key criteria necessary for their evolution and maintenance as cues in
      mate assessment; that is, they should exhibit variation across individuals within
      a sex and species; they should honestly reflect an individual's quality and thus
      be costly to produce and/or maintain; they should display relatively high levels
      of heritability. There is now substantial empirical evidence that pheromones can
      satisfy all these criteria and, while measurements of the actual metabolic cost
      of pheromone production remain to some degree lacking, trade-offs between
      pheromone production and various fitness-related characters such as growth rate,
      immunocompetence and longevity have been reported for a range of species. In the
      penultimate section, we outline the growing number of studies where the
      consequences of chemical-based mate assessment have been investigated,
      specifically focussing on the reported direct and genetic benefits accrued by the
      receiver. Finally, we highlight potential areas for future research and in
      particular emphasise the need for interdisciplinary research that combines
      exploration of chemical, physiological and behavioural processes to further our
      understanding of the role of chemical cues in mate assessment.

PMID- 17437562
TI  - Integrating animal temperament within ecology and evolution.
AB  - Temperament describes the idea that individual behavioural differences are
      repeatable over time and across situations. This common phenomenon covers
      numerous traits, such as aggressiveness, avoidance of novelty, willingness to
      take risks, exploration, and sociality. The study of temperament is central to
      animal psychology, behavioural genetics, pharmacology, and animal husbandry, but
      relatively few studies have examined the ecology and evolution of temperament
      traits. This situation is surprising, given that temperament is likely to exert
      an important influence on many aspects of animal ecology and evolution, and that
      individual variation in temperament appears to be pervasive amongst animal
      species. Possible explanations for this neglect of temperament include a
      perceived irrelevance, an insufficient understanding of the link between
      temperament traits and fitness, and a lack of coherence in terminology with
      similar traits often given different names, or different traits given the same
      name. We propose that temperament can and should be studied within an
      evolutionary ecology framework and provide a terminology that could be used as a
      working tool for ecological studies of temperament. Our terminology includes five
      major temperament trait categories: shyness-boldness, exploration-avoidance,
      activity, sociability and aggressiveness. This terminology does not make
      inferences regarding underlying dispositions or psychological processes, which
      may have restrained ecologists and evolutionary biologists from working on these
      traits. We present extensive literature reviews that demonstrate that temperament
      traits are heritable, and linked to fitness and to several other traits of
      importance to ecology and evolution. Furthermore, we describe ecologically
      relevant measurement methods and point to several ecological and evolutionary
      topics that would benefit from considering temperament, such as phenotypic
      plasticity, conservation biology, population sampling, and invasion biology.

PMID- 17437563
TI  - Paternal kin discrimination: the evidence and likely mechanisms.
AB  - One of the most important assumptions of kin selection theory is that individuals
      behave differently towards kin than non-kin. In mammals, there is strong evidence
      that maternal kin are distinguished from non-kin via familiarity. However, little
      is known about whether or not mammals can also recognize paternal kin as many
      female mammals, including primates, mate with multiple males near the time of
      conception, potentially concealing paternal kinship. Genetic data in several
      mammalian species with a promiscuous mating system and male-biased dispersal
      reveal a high skew in male reproduction which leads to co-residing paternal half
      siblings. In most primates, individuals also form stable bisexual groups creating
      opportunities for males to interact with their offspring. Here I consider close
      paternal kin co-resident in the same social group, such as father-offspring and
      paternal half-siblings (i.e. animals sharing the same father but who were born to
      different mothers) and review mammalian studies of paternal kin discrimination.
      Furthermore, I summarize the most likely mechanisms of paternal kin
      discrimination (familiarity and phenotype matching). When familiarity is the
      underlying mechanism, mothers and/or the sire could mediate familiarity among
      paternal half-siblings as well as between fathers and offspring assuming mothers
      and/or fathers can assess paternity. When animals use phenotype matching, they
      might use their fathers' template (when the father is present) or self (when the
      father is absent) to assess paternal kinship in others. Available evidence
      suggests that familiarity and phenotype matching might be used for paternal kin
      discrimination and that both mechanisms might apply to a wide range of social
      mammals characterized by a high skew in male reproduction and co-residence of
      paternal kin. Among primates, suggested evidence for phenotype matching can often
      have an alternative explanation, which emphasizes the crucial importance of
      controlling for familiarity as a potential confounding variable. However, the
      mechanism/s used to identify paternal kin might differ within a species (as a
      function of each individual's specific circumstances) as well as among species
      (depending upon the key sensory modalities of the species considered). Finally, I
      discuss the possible cues used in paternal kin discrimination and offer
      suggestions for future studies.

PMID- 17437565
TI  - Is the twist hazardous to your health?

PMID- 17437566
TI  - Sporadic isolated left ventricular noncompaction: dread disease or not?

PMID- 17437567
TI  - Clinical implications of various follow up strategies after catheter ablation of
      atrial fibrillation.

PMID- 17437568
TI  - Quality of life among implantable cardioverter-defibrillator recipients in the
      primary prevention therapeutic era.
AB  - BACKGROUND: Although patients receiving implantable cardioverter-defibrillators
      (ICDs) for primary prevention of sudden cardiac death are the fastest growing
      segment of the ICD recipient population, the quality-of-life (QOL) effects of the
      ICD among primary prevention patients are not well understood. The purpose of
      this study was to measure and compare the health-related QOL among primary and
      secondary prevention ICD recipients, and to determine predictive factors for high
      or low QOL in each group. METHODS: Forty-five primary prevention and 75 secondary
      prevention ICD recipients receiving routine care in electrophysiology clinics
      within the University of Pennsylvania Health System were assessed using several
      well-validated general and ICD-specific QOL instruments. RESULTS: Between primary
      and secondary prevention patients, there were no significant differences in
      EuroQol 5D (medians: 0.84 vs 0.84, P = 0.71), Health Utilities Index (medians:
      0.88 vs 0.85, P = 0.95), Short Form-12 aggregate physical summary (means: 45 vs
      46, P = 0.64), and Short Form-12 aggregate mental summary (means: 46 vs 47, P =
      0.93) scores. Both primary and secondary prevention patients viewed their devices
      favorably according to the Florida Patient Acceptance Survey scale, with no
      significant differences between group means (80 vs 83, P = 0.71). However,
      substantial fractions of both primary and secondary prevention recipients had
      particular concerns about lifting (40%), sexual activity (19%), and driving
      (14%). CONCLUSIONS: QOL does not significantly differ between primary prevention
      and secondary prevention ICD recipients. Device recipients had comparable QOL to
      published, nationwide QOL estimates among non-ICD patients of similar age. The
      ICD was highly acceptable to most primary and secondary prevention patients.

PMID- 17437569
TI  - Electromagnetic interference from wireless video-capsule endoscopy on implantable
      cardioverter-defibrillators.
AB  - OBJECTIVES: The purpose of this study was to evaluate potential interference
      between the Pill-cam video-capsule and implanted cardio-defibrillators (ICD) in
      both in vitro and in vivo test environments. METHODS: Phase I consisted of in
      vitro testing utilized 6 ICD models. Each was placed in a saline gel bath in
      conjunction with a tool designed to emit the same wave length as the Pill-Cam
      (the Test Cap). Tests were performed at both the manufacturer's nominal and most
      sensitive settings with the test probe placed at 1, 5, 10, and 15 cm from three
      different points. There were emissions of 10-, 30-, and 60- second duration at
      each location. Phase II was the in vivo study utilizing patients with implanted
      ICDs for standard clinical reasons who were undergoing evaluation with the Test
      Cap. RESULTS: In Phase I, 864 tests were performed involving the 6 ICDs. There
      was totally normal behavior in 5 of the devices. The Biotronik Belos (Berlin,
      Germany) demonstrated oversensing and delivery of inappropriate therapy. In phase
      II, 6 patients underwent a total number of 288 tests (48 in each patient). There
      were 4 men and 2 women, mean age 61 (33-77) and none demonstrated any adverse
      interactions. CONCLUSIONS: In patients with devices identical to those evaluated
      that showed no interference, the use of the Pill-Cam is safe. However, in
      patients with a Biotronik Belos ICD (or any other nontested ICD) the use of the
      Pill-Cam should be done only in-hospital, after suspended ICD therapy and in
      conjunction with close monitoring.

PMID- 17437570
TI  - Optimal sensed atrio-ventricular interval determined by paced QRS morphology.
AB  - BACKGROUND: In cardiac resynchronization therapy (CRT), the atrio-ventricular
      (AV) and interventricular (VV) intervals have to be optimized. For maximal
      optimization, the paced and sensed AV intervals have to be determined. We
      hypothesized that the morphology of the paced QRS complex at the optimal paced AV
      interval (PAV) can be used to determine the optimal sensed AV (SAV) interval in
      patients with normal AV conduction. PATIENTS AND METHODS: In 16 patients with
      implanted CRT devices, the optimal PAV and V-V interval were determined by
      invasive measurement of left ventricle (LV) dP/dt(max). A 12-lead
      electrocardiogram (ECG) was recorded at the optimum setting. Subsequently, during
      atrial sensing ventricular pacing, the SAV interval was changed until the QRS
      morphology was identical to the morphology at the optimal PAV interval. The
      optimal SAV interval was verified by repeated measurement of LV dP/dt(max).
      RESULTS: By optimization of the PAV and VV interval, the LV dP/dt(max) increased
      from 639 +/- 204 to 789 +/- 223 mmHg/s (+23%; P = 0.0000002). The optimized PAV
      was 149 +/- 19 ms; the optimized SAV was 100 +/- 20 ms and the corresponding LV
      dP/dt(max) at this interval was 774 +/- 204 ms (+21%; P = 0.000004). LV
      dP/dt(max) at optimized SAV - 20 ms and optimized SAV + 20 ms was 747 +/- 213
      mmHg/s (P = 0.00004) and 751 +/- 203 mmHg/s (P = 0.0000003), respectively. The
      mean difference in optimized PAV and optimized SAV was 49 +/- 17 ms, ranging from
      20 to 80 ms. CONCLUSIONS: The QRS morphology at optimized PAV can be used as a
      template to determine the optimal SAV, provided that the patient has normal AV
      conduction.

PMID- 17437571
TI  - The right ventricular outflow tract: the road to septal pacing.
AB  - BACKGROUND: Pacing from the right ventricular apex is associated with long-term
      adverse effects on left ventricular function. This has fuelled interest in
      alternative pacing sites, especially the septal aspect of the right ventricular
      outflow tract (RVOT). However, it is a common perception that septal RVOT pacing
      is difficult to achieve. METHODS AND RESULTS: In this article, we will review the
      anatomy of the RVOT and discuss the importance of standard radiographic views and
      the 12-lead electrocardiogram in aiding lead placement. We will also describe a
      method utilizing a novel stylet shape, whereby a conventional active-fixation,
      stylet-driven lead can be easily and reliably deployed onto the RVOT septum.

PMID- 17437572
TI  - Adaptive bi-atrial pacing improves the maintenance of sinus rhythm.
AB  - INTRODUCTION: Multiple pacing modalities have been shown to individually decrease
      atrial fibrillation (AF) burden and relieve symptoms of AF. This investigation
      retrospectively evaluated whether a combination of bi-atrial pacing with dynamic
      atrial overdrive (DAO) AF suppression would further decrease AF burden as
      compared to AF suppression (DAO) alone. METHODS AND RESULTS: A total of 33
      patients were retrospectively evaluated. Patients (n = 16) were identified from
      the Deborah Heart and Lung Center pacemaker database with DAO programmed on at
      time of implantation. Patients (n = 17) were identified with bi-atrial pacing
      leads in right atrium and mid to distal coronary sinus who also had DAO
      programmed on at the time of implant. Evaluation of interrogated pacing data
      revealed Percent Time in Mode Switch (18.2%+/- 7.2% vs 0.59%+/- 0.08%) to be
      significantly lower (P = 0.014) in the bi-atrial paced group. In addition, there
      were less mode switches per day (MSPD) in the bi-atrial paced group (0.62 +/-
      0.43 MSPD) versus control (4.40 +/- 3.24 MSPD) (P = 0.06). CONCLUSION: Bi-atrial
      pacing while used in conjunction with an adaptive pacing suppression algorithm
      (DAO) may successfully be used to inhibit PAF.

PMID- 17437573
TI  - Cardiac tamponade as complication of active-fixation atrial lead perforations:
      proposed mechanism and management algorithm.
AB  - BACKGROUND: Cardiac tamponade is a rare complication after implantation of dual
      chamber pacemaker or defibrillator systems. Its pathophysiology and optimal
      management are not currently well established. METHODS: Three cases of cardiac
      tamponade following successful implantation of transvenous dual chamber
      pacemakers with active-fixation atrial leads were identified. RESULTS: All three
      patients with post-implant cardiac tamponade were suspected to have the same
      etiology of bleeding into the pericardial space. This was due to protrusion of
      the helix of the active-fixation atrial pacing lead through the atrial wall with
      subsequent abrasion of visceral pericardial layer and bleeding from the atrium
      through the perforation. In two patients, the perforation sites were visualized
      and repaired during open thoracotomy in the operating room. The third patient
      underwent lead repositioning under fluoroscopic guidance in the electrophysiology
      laboratory. CONCLUSION: Based on the reviewed cases, we describe the
      pathophysiology of, and recommend a safe conservative algorithm for, the
      management of cardiac tamponade after successful transvenous lead implantation.
      Percutaneous pericardiocentesis with placement of the pericardial drain followed
      by lead repositioning under fluoroscopic guidance with surgical backup appears to
      be safe and effective.

PMID- 17437574
TI  - Reverse electrical remodeling of the atria post cardioversion in patients who
      remain in sinus rhythm assessed by signal averaging of the P-wave.
AB  - OBJECTIVES: This study was designed to determine whether the signal-averaged
      electrocardiogram of the P-wave (SAPW) is an independent predictor of recurrence
      of atrial fibrillation (AF) post cardioversion (CV), and to assess atrial
      remodeling using SAPW. BACKGROUND: There are limited electrophysiologic data to
      predict the recurrence of AF post-CV. The electrical remodeling that occurs post
      CV is poorly understood. METHODS: Sixty-four patients with persistent AF
      undergoing CV were prospectively enrolled. SAPW parameters were measured the day
      of CV and repeated at 1 month. These SAPW parameters were compared to other
      baseline indices for the recurrence of AF. RESULTS: Sixty patients (94%) had
      successful CV. At 1 month, 22 (37%) maintained sinus rhythm (SR). The SAPW total
      duration decreased significantly in those who remained in SR (159 ms +/- 19 to
      146 ms +/- 17; P < 0.0001). Only the duration of AF (46 +/- 50 days vs 147 +/-
      227 days, P = 0.03) and the presence of left ventricular hypertrophy (LVH, 12% vs
      65%, P = 0.0006) were significantly associated with recurrence of AF. Atrial size
      strongly correlated with the SAPW duration in patients who remained in SR (R(2)=
      0.67, P = 0.003) but not in those who returned to AF (R(2)= 0.11, P = 0.65).
      CONCLUSIONS: Atrial electrical reverse remodeling occurs in patients with AF who
      maintain SR post-CV. This remodeling is likely inversely related to the duration
      of AF and LVH. SAPW duration does not predict recurrence of AF post-CV.

PMID- 17437575
TI  - Elimination of fluoroscopy use in a pediatric electrophysiology laboratory
      utilizing three-dimensional mapping.
AB  - OBJECTIVES: The aim of this study was to quantify fluoroscopy use in catheter
      ablation procedures using a three-dimensional mapping system as the primary
      source of catheter guidance. BACKGROUND: Three-dimensional mapping allows
      continuous visualization of the location of mapping and ablation catheter
      electrodes. It has been shown to decrease fluoroscopy times. However, the extent
      to which it can decrease fluoroscopy time has not been completely defined.
      METHODS: Thirty patients (mean age 12.9 years; range 4-27 years) with reentrant
      supraventricular tachycardia underwent catheter ablation using standard
      protocols. Mapping was performed using the EnSite system (St. Jude Medical, St
      Paul, MN, USA) in the NavX mode (NavX). Eighteen patients had AVNRT, 12 had AVRT.
      Fluoroscopy times were compared to an age-matched and rhythm-matched control
      population. RESULTS: Procedural success was achieved in 30 of 30 patients (100%).
      Mean procedure time was 3.27 hours (range 1.83-5.8 hours). Mean fluoroscopy time
      was 1.05 minutes (range 0-14.8 minutes). Twenty-four of 30 (80%) received no
      fluoroscopy. Mean fluoroscopy time for the control group was 21.37 minutes (range
      5.13-77.13 minutes). Thus fluoroscopy time was 95% less in the study group
      compared to control (1.05 +/- 2.96 vs 21.37 +/- 18.35 minutes, P < 0.001).
      CONCLUSIONS: NavX was used to effectively guide catheters during ablation
      procedures resulting in a significant decrease in fluoroscopy use. In 80% of the
      procedures, no fluoroscopy was used. Further advances in the technology may
      permit additional decreases in x-ray exposure for the 20% of patients who
      required it.

PMID- 17437576
TI  - A nonfluoroscopic approach for electrophysiology and catheter ablation procedures
      using a three-dimensional navigation system.
AB  - BACKGROUND: Three-dimensional (3D) electroanatomical navigation systems decrease
      the fluoroscopy time of electrophysiology and ablation procedures. The aim of
      this study was to assess the safety and efficacy of a complete nonfluoroscopic
      approach for electrophysiologic studies and right-sided catheter ablations for
      supraventricular tachycardia in patients with normal cardiac anatomy using a 3D,
      surface electrode-based navigation system (NavX, St. Jude Medical, St. Paul, MN,
      USA). METHODS AND RESULTS: Electrophysiologic studies were performed in 26
      consecutive cases (12.7 +/- 7.5 years) using NavX without fluoroscopy. The
      procedure time was 98.7 +/- 49.7 minutes. Nonfluoroscopic catheter ablations were
      performed in 24 of 28 consecutive patients. Cryoablation was used in 23 of 24.
      The procedure time was 193.5 +/- 80 minutes. The coronary sinus access was
      obtained in 32.1 +/- 12 (range: 15-60) seconds. No complications occurred. All
      patients (n = 19) who underwent cryoablation for right-sided arrhythmia
      substrates with conventional fluoroscopic guidance in addition to NavX were used
      as a control group (10.1 +/- 5.2 years). Catheter ablation success rate of the
      control group (16/19, 84%) was not significantly different compared to the
      patients who underwent ablation without fluoroscopy (22/24, 92%). The procedure
      time was also not significantly different between the two groups (P = NS).
      CONCLUSION: This study demonstrates that nonfluoroscopic electrophysiologic
      studies and right-sided catheter ablations for supraventricular tachycardia can
      be safely and effectively performed in the majority of patients with normal
      cardiac anatomy using NavX. Further studies will be necessary in order to
      establish the potential utility of NavX in eliminating or decreasing radiation
      exposure for other electrophysiology procedures.

PMID- 17437577
TI  - Radiofrequency ablation of the ventricular tachycardia with arrhythmogenic right
      ventricular cardiomyopathy using non-contact mapping.
AB  - BACKGROUND: Intracardiac non-contact mapping provides a rapid and accurate
      isopotential mapping that facilitates catheter ablation of the ventricular
      tachyarrhythmias in arrhythmogenic right ventricular cardiomyopathy (ARVC).
      METHODS: Thirty-two consecutive patients (26 men and 6 women, mean 37.2 +/- 13.8
      years) were treated with ablation. Fourteen patients had a history of syncope/pre
      syncope. Two patients had an implantable cardiac defibrillator (ICD) previously
      implanted. RESULTS: There were 67 ventricular tachycardias (VTs) induced in the
      32 patients. The average VT rate was 210 +/- 32.2 (130-310) bpm. There were 42
      episodes of VT that had a heart rate > or =200 bpm and 24 of the 32 patients
      (75%) had > or =2 morphologies of VT. Regional ablation was applied by targeting
      the earliest VT activation sites under the guidance of non-contact mapping. Acute
      success was achieved in 84.4% (27/32) patients, and significant improvement was
      seen in 15.6% (5/32) patients as evidenced by a slower rate of VT. None of the
      patients experienced syncope/pre-syncope or sudden death during the 28.6 +/- 16
      (9-72) month follow-up. There were no complications of the procedure. At the end
      of follow-up, 81.3% of the patients were free of VT without medication while the
      rest of the patients achieved a modified success. CONCLUSIONS: The rapid
      ventricular tachyarrhythmias in ARVC patients can be abolished or improved
      significantly by regional RF catheter ablation under the guidance of non-contact
      mapping. There was no sudden cardiac arrest or death in those patients without
      ICD implantation. Delayed efficacy may occur in some patients after ablation.

PMID- 17437578
TI  - Demonstration of ventricular myocardial extensions into the pulmonary artery and
      aorta beyond the ventriculo-arterial junction.
AB  - BACKGROUND: A subgroup of outflow tract (OT) ventricular tachycardias (VT)
      originate from the aortic sinuses or the main stem of the pulmonary artery. The
      anatomic substrate for these tachycardias is unknown. The aim of this study was
      to investigate the presence of ventricular myocardial extensions (VME) into the
      pulmonary artery (PA) and aorta (Ao) beyond the ventriculo-arterial junction
      (VAJ) and determine the anatomical and histological characteristics of these
      muscle extensions. METHODS: Ninety-five consecutive human hearts obtained at
      autopsy were studied. Longitudinal strips of tissue containing each cusp, aortic,
      and pulmonary artery walls and left and right ventricular outflow tracts were
      excised and histologically analyzed. Anatomical measurements, including length
      and thickness of VMEs, obtained at autopsy, were made. RESULTS: VMEs beyond the
      VAJ were found in 21 of 95 (22%) patients studied. VMEs were found in 16 of 95
      PAs (17%) and 7 of 95 Aos (7%) were examined. VMEs were located within the
      adventitia in 23 (88%) and on the epicardial surface in three (12%). The majority
      of VMEs were in continuity with the underlying ventricular OT muscle tissue.
      Myocellular hypertrophy and fibrosis were present in 19 (73%) and fatty tissue
      between the layers of VME in 18 (69%). Clinical data were available in 14 of 21
      patients with positive VME. None of the patients (clinical data available group)
      had history of cardiac disease or signs or symptoms (palpitations or syncope) of
      cardiac disease. CONCLUSIONS: VMEs into the PA and Ao beyond the VAJ are
      relatively common. It seems that their mere presence does not predispose to OT
      VTs. There are probably intrinsic arrhythmogenic properties in tissues specific
      to these regions in those patients who develop OT VTs.

PMID- 17437579
TI  - Influence of comorbidities and medication use on tilt table test outcome in
      elderly patients.
AB  - BACKGROUND: The tilt table test (TTT) is a useful diagnostic tool in people with
      unexplained syncope, dizziness, and falls. However, preexisting comorbidities and
      medications affecting hemodynamic response might affect TTT outcome (i.e.
      presence or absence of vasomotor syncope). We studied the influence of these
      compounding factors on TTT outcome. METHODS: One hundred and sixty-four elderly
      patients with a mean (+/-SD) age of 80.0 +/- 6.1 years (M:F 104:60) underwent
      TTT. Heart rate and blood pressure were recorded continuously using a noninvasive
      device (Task Force Monito, CNS systems, Graz, Austria). Predictors of TTT outcome
      in a backward regression analysis included age, gender, comorbidities (chronic
      heart failure, hypertension, diabetes, and cerebrovascular disease), and drugs
      (beta-blockers, angiotensin-converting enzyme inhibitors, calcium channel
      blockers, diuretics, digoxin, opioids, antidepressants, and nonsteroidal
      antiinflammatory agents). RESULTS: TTT was positive in 30 patients (18.3%). None
      of the above factors were a significant predictor of TTT outcome. The use of
      calcium channel blockers predicted a drop in systolic blood pressure after 2
      minutes of TTT (P = 0.048, R(2)= 0.018). However, this was not associated with
      significant changes in heart rate and did not influence TTT outcome. CONCLUSION:
      The TTT outcome was not influenced by comorbidities or medications. TTT is a
      reliable diagnostic tool in a population characterized by significant
      comorbidities and polypharmacy.

PMID- 17437580
TI  - Ventricular tachycardia in non-compaction of left ventricle: is this a frequent
      complication?
AB  - BACKGROUND: Isolated left ventricular non-compaction is the result of incomplete
      myocardial morphogenesis, leading to persistence of the embryonic myocardium. The
      condition is recognized by an excessively prominent trabecular meshwork and deep
      intertrabecular recesses of the left ventricle. Whether these intertrabecular
      recesses are a favorable substrate for ventricular arrhythmias is unclear. Some
      reports have found that the fatal ventricular arrhythmias may occur in
      approximately half of the patients. In this report we investigated about this
      association. METHODS AND RESULTS: In total we evaluated a continuous series of
      238 patients affected by non-compaction. Periodic Holter monitoring was performed
      every 6 months for 4 years. Only 11 patients had documented ventricular
      tachycardia, which was sustained in two cases and non-sustained in nine. In no
      cases we observed ventricular fibrillation. CONCLUSIONS: Non-compaction alone
      does not seem to be a risk factor for malignant ventricular arrhythmias.

PMID- 17437581
TI  - Transition of narrow into wide complex tachycardia with left bundle branch block
      morphology and varying QRS duration: what is the mechanism?

PMID- 17437582
TI  - VF and fatal cardiac arrest following ICD therapy delivery: what is the cause?

PMID- 17437583
TI  - Electrical cardioversion for AF-the state of the art.

PMID- 17437584
TI  - Transvenous implantation of a coronary sinus lead for left ventricular pacing
      after cutting balloon angioplasty.
AB  - We describe a patient in whom a localized proximal vein stenosis at the only
      possible target vein precluded placement of a coronary sinus lead for left
      ventricular (LV) pacing. After multiple attempts to perform venoplasty with both
      compliant and noncompliant balloons, a cutting balloon relieved the obstruction,
      and an LV pacing lead was successfully placed in the midportion of this lateral
      vein.

PMID- 17437585
TI  - Implantation of a biventricular implantable cardioverter defibrillator via the
      femoral vein.
AB  - Permanent pacing with access gained via the femoral vein has been described since
      1980. Here we describe implantation of a biventricular implantable cardioverter
      defibrillator (ICD) in a case where normal implantation using thoracic venous
      access was not possible due to anatomical anomalies. The advantages of this
      technique over epicardial pacing in such a case are discussed, as are the
      practical difficulties involved when applying this technique to the implantation
      of a biventricular ICD.

PMID- 17437586
TI  - A left-sided accessory pathway revisited with remote retrograde magnetic
      navigation.
AB  - Accessory pathways can be ablated with a high success rate. Occasionally,
      recurrences appear after successful procedures, sometimes shortly after the end
      of the procedure. We describe a successful ablation using remote magnetic
      navigation of a single catheter using stored vectors after recurrence of
      accessory pathway conduction while the patient was still in the electrophysiology
      laboratory.

PMID- 17437587
TI  - Uncommon etiology of syncope in a patient with isolated ventricular
      noncompaction.
AB  - Isolated noncompaction of left ventricular myocardium (IVNC) is categorized as an
      unclassified cardiomyopathy by the World Health Organization. We describe the
      case of a 29-year-old woman who was diagnosed with IVNC after suffering two
      syncopes caused by an atrioventricular nodal reentrant tachycardia (AVNRT) that
      was successfully ablated. We report successful radiofrequency ablation in an
      adult with this cardiomyopathy. Although the presence of syncope in these
      patients obliged us to rule out a ventricular tachycardia as the most probable
      etiology, our case shows how an exhaustive study is needed to look for other
      possible and curable causes.

PMID- 17437588
TI  - Value of pacemaker atrial diagnostic data in patients with paroxysmal atrial
      fibrillation: an opportunity to improve rates of warfarin utilization.
AB  - Atrial diagnostic data within implantable devices provide an opportunity to
      assess the frequency and quantity of atrial fibrillation (AF) episodes (AF
      burden) and its impact on appropriate warfarin anticoagulation. Cardiologists
      were given clinical scenarios to review with different types of pacemaker
      diagnostic data in an elderly patient with risk factors for stroke. AF specific
      data was associated with increased warfarin utilization, but only at intermediate
      rates. Potential reasons and clinical implications are discussed.

PMID- 17437589
TI  - Dislodgement of atrial lead of the CRT-D system and its migration into the pocket
      presenting as its absence on chest x-ray.
AB  - Lead dislodgement and migration is a known complication after implantation of
      cardiac rhythm devices. We present a case of dislodgement of atrial lead of the
      CRT-D system and its migration into the device pocket. The device itself had
      rotated by 90 degrees but the right and left ventricular leads were not at all
      affected. The case is unique because the lead had coiled up and was lying behind
      the device in the pocket and hence was not even seen on a chest x-ray.

PMID- 17437590
TI  - Panic attack like episodes possibly associated with pramipexole therapy in
      Parkinson's disease.

PMID- 17437591
TI  - Spontaneous cerebrospinal fluid hypovolaemia: a therapeutic dilemma?

PMID- 17437599
TI  - Superficial siderosis of the CNS: selective central myelin vulnerability and
      peripheral myelin sparing demonstrated by MRI.

PMID- 17437600
TI  - Change of brain MRI findings in a patient with intravascular malignant
      lymphomatosis.

PMID- 17437601
TI  - Oculopalatal and cerebellar limb tremor due to hypertrophic olivary degeneration.

PMID- 17437602
TI  - Cardioembolic stroke and ischemic small bowel infarction in a Chagas' disease
      patient.

PMID- 17437603
TI  - IVIg-induced acute polyneuroradiculitis in a patient with CIDP?

PMID- 17437604
TI  - The influence of anaemia on stroke prognosis and its relation to N-terminal pro
      brain natriuretic peptide.
AB  - Anaemia is a negative prognostic factor for patients with heart failure and
      impaired renal function, but its role in stroke patients is unknown. Furthermore,
      anaemia has been shown to influence the level of N-terminal pro-brain natriuretic
      peptide (NT-proBNP), but this is only investigated in patients with heart
      failure, not in stroke patients. Two-hundred-and-fifty consecutive, well-defined
      ischemic stroke patients were investigated. Mortality was recorded at 6 months
      follow-up. Anaemia was diagnosed in 37 patients (15%) in whom stroke severity was
      worse than in the non-anaemic group, whilst the prevalence of renal affection,
      smoking and heart failure was lower. At 6 months follow-up, 23 patients were
      dead, and anaemia had an odds ratio of 4.7 when adjusted for age, Scandinavian
      Stroke Scale and a combined variable of heart and/or renal failure and/or
      elevation of troponin T using logistic regression. The median NT-proBNP level in
      the anaemic group was significantly higher than in the non-anaemic group, and in
      a multivariate linear regression model, anaemia remained an independent predictor
      of NT-proBNP. Conclusively, anaemia was found to be a negative prognostic factor
      for ischemic stroke patients. Furthermore, anaemia influenced the NT-proBNP level
      in ischemic stroke patients, an important aspect when interpreting NT-proBNP in
      these patients.

PMID- 17437605
TI  - Neurologic manifestations of ulcerative colitis.
AB  - Ulcerative colitis (UC) has traditionally been considered to be an inflammatory
      disease limited to the colonic mucosa. However, since it has been shown that UC
      is frequently accompanied by various extraintestinal disorders, there is
      increasing evidence that UC may also manifest in the nervous system. The
      following review focuses particularly on these possible manifestations of UC,
      both in the peripheral (PNS), and in the central nervous system (CNS). A
      systematic literature search according to the MEDLINE database was performed for
      this purpose. Although a reliable differentiation may clinically not always be
      possible, three major pathogenic entities can be differentiated: (i)
      cerebrovascular disease as a consequence of thrombosis and thromboembolism; (ii)
      systemic and cerebral vasculitis; (iii) probably immune mediated neuropathy and
      cerebral demyelination. With the exception of thromboembolism and sensorineural
      hearing loss, evidence for a causal relationship relies merely on single case
      reports or retrospective case series. Considering the CNS-manifestations,
      similarities between UC-associated disorders of the white matter and acute
      disseminated encephalomyelitis (ADEM) are obvious. Epileptic seizures,
      unspecified encephalopathies and confusional states are most likely epiphenomena
      that have to be regarded symptomatic rather than as own entities. A prospective
      study on the neurologic aspects of UC would be very welcome.

PMID- 17437606
TI  - Contribution of clinical screening to carrier detection in a large Chinese family
      with Fabry disease due to a novel alpha-galactosidase A gene deletion.
AB  - Diagnosis of heterozygous Fabry patients is difficult because of its variable
      clinical manifestations and overlapping serum alpha-galactosidase A (AGA)
      activity between carriers and non-carriers. We tried to facilitate diagnosis of
      heterozygous Fabry patients by detailed clinical examination. We analyzed
      clinical presentations, biochemical, electrophysiological and genetic
      characteristics of 16 patients with Fabry disease in a large Chinese family. Male
      patients demonstrated significantly higher pain scores, poorer renal function,
      and higher frequency of hypohidrosis and corpora angiokeratomas than female
      patients. Interestingly, all the males and females had corneal verticilata by
      slit lamp examination. However, there was no association of serum AGA activity
      with renal function or pain symptom scores. The results indicated that detailed
      ocular and neurological examination might provide an alternative way of detecting
      heterozygous patients. We also report a novel large deletion spanning across the
      joint of Alu repetitive elements in introns 1 and 2 with resultant exon 2
      deletion in a Chinese family with Fabry disease.

PMID- 17437607
TI  - A study of clinical, MRI and multimodality evoked potentials in neurologic Wilson
      disease.
AB  - The aims of this study were evaluate motor, somatosensory, visual and auditory
      brainstem evoked potential (MEP, SEP, VEP, ABER) changes in Wilson disease (WD)
      and correlate these with magnetic resonance imaging (MRI) and clinical findings.
      Neurologic WD diagnosed on the basis of clinical, ceruloplasmin and Kayser
      Fleischer ring were evaluated including pedigree charting, hepatic, renal,
      hematologic and osteoarticular manifestations. Blood counts, serum chemistry,
      MRI, MEP to tibialis anterior, tibial SEP, VEP and ABER were performed. Evoked
      potential (EP) changes were correlated with clinical and MRI findings. Eighteen
      WD patients were recruited from 17 families whose mean age was 16 years. Movement
      disorders were present in 14, cognitive decline in 12 and pyramidal signs in 12
      patients. MRI revealed involvement of basal ganglia in 80%, thalamus in 40%,
      brain stem in 46.7% and subcortical white matter in 53.3%. MEP was abnormal in
      35.7%, SEP in 30.8%, VEP in 57% and ABER in 61.5% patients; the latter three EP
      changes were subclinical. Frequency and number of EP abnormalities were higher
      with increasing severity of illness. SEP, VEP and ABER reveals subclinical
      abnormality and MEP helps in documenting both clinical and subclinical
      abnormalities. Number of EP abnormalities increases with increasing clinical
      severity of WD.

PMID- 17437608
TI  - Education and training of European neurologists in dementia.
AB  - The aim of this study was to describe the present involvement of neurologists in
      dementia management in European countries. Data were obtained from a
      questionnaire that members of The European Federation of Neurological Societies
      Scientific Panel on Dementia responded to. Information was obtained from 25
      countries in Europe. A progressive decrease in the teaching activity from medical
      school to board-certified neurologists was reported. Teaching of medical students
      in dementia is obligatory in most countries, whereas there is no formal
      obligatory education in dementia after graduation from medical school. Further,
      in only half of the countries that responded to the questionnaire, obligatory
      courses in dementia are part of the training in neurology. Except for one
      country, the post-graduate training programs of board-certified neurologists do
      not include dementia as an obligatory topic. In only 10 of 25 countries,
      guidelines for neurologists on dementia evaluation have been published in local
      language. It is recommended to include obligatory teaching and training in
      dementia in the catalogue of minimum requirements for specialist training in
      neurology and this teaching should also be part of the ongoing update of
      certified neurologists.

PMID- 17437609
TI  - Gelatinolytic activity of matrix metalloproteinase-2 and matrix metalloproteinase
      9 in rat brain after implantation of 9L rat glioma cells.
AB  - The matrix metalloproteinases (MMPs) have come to be highlighted by their close
      relation to the cell invasion of gliomas. The inhibitors of MMPs have undergone
      extensive development because of its effectiveness against tumor invasion and
      angiogenesis. Therefore, a suitable animal model is necessary for searching new
      MMPs inhibitors against gliomas. In this study, we established an experimental
      model by implanting 9L glioma cells stereotactically into Fisher344 (F344) rat's
      brain, and the expression and enzymatic activity of MMP-2 and MMP-9 in 9L glioma
      cells and in tumor tissue was determined by means of reverse transcription
      polymerase chain reaction (RT-PCR), sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) zymography, in situ film zymography and
      immunostaining. The results of RT-PCR showed that the mRNA level of MMP-2 in 9L
      glioma cells was higher than that of MMP-9, and the mRNA expression of MMP-9 was
      increased along with the growth of malignant gliomas. SDS-PAGE zymography
      revealed that the expression of MMP-2 and MMP-9 were significantly increased in
      tumor tissues, and the MMP-9 wasn't detected in normal tissue. The positive stain
      of MMP-2 and MMP-9 was enhanced with the growth of malignant gliomas, especially
      for MMP-9. The expression of active gelatinase was found in tumor tissue. In
      conclusion, the expression of active MMP-2 and MMP-9 was increased in 9L/F344 rat
      brain during the growth of malignant gliomas at different time intervals, which
      indicate that 9L/F344 animal model may be a prospective animal model to test new
      MMPs inhibitors.

PMID- 17437610
TI  - A population-based study on awareness of stroke in Turkey.
AB  - Stroke is the second most common cause of mortality and a major cause of long
      term disability of adults in most countries. This study was performed to
      determine the level of knowledge and awareness regarding risk factors and warning
      signs of stroke in a selected sample. This cross-sectional study was carried out
      in Aydin between November and December 2005, utilizing a study sample of 920
      people registered at urban health centers. The questionnaire, prepared by the
      investigators, was administered by 20 trained students utilizing face-to-face
      interviews at participants' homes. Two-thirds of the participants knew the organ
      effected by stroke. The participants reported that stroke was a consequence of
      occlusion (28.0%) or bleeding (18.0%) in brain arteries. Paralysis/weakness of
      one side of the body (37.1%), speech impairment (26.8%) and numbness of one side
      of the body (14.2%) were reported as three major stroke warning signs. Sixty-four
      percent of the participants knew at least one of these risk factors. Their
      primary sources of information were family and friends. Our study showed the
      great need for increasing awareness of risk factors and warning signs for stroke,
      perhaps utilizing community based education programs and the mass media.

PMID- 17437612
TI  - Plasma lipid peroxidation and progression of disability in multiple sclerosis.
AB  - Oxidative stress has been implicated in the pathophysiology of multiple sclerosis
      (MS), but its relation to disease progression is uncertain. To evaluate the
      relationship of plasma lipid peroxidation with progression of disability in MS,
      we measured blood plasma fluorescent lipid peroxidation products (PFLPP) levels
      in 23 patients with RRMS with a benign course, 32 with secondary progressive MS,
      24 with primary progressive MS and 30 healthy controls. None of the patients had
      a relapse within the previous 3 months. Progression of disability was evaluated
      during a follow-up period of 5 years by the Expanded Disability Status Scale
      (EDSS) and the Multiple Sclerosis Severity Score (MSSS). We found plasma PFLPP
      levels elevated in patients with MS compared with controls (P < 0.0001), but
      there was no difference between patients with a benign and progressive disease
      course. There was no correlation between PFLPP levels and worsening of disability
      on the EDSS and speed of progression on the MSSS. Our data suggest that there is
      no relation between the degree of oxidative stress in plasma and progression of
      disability in MS.

PMID- 17437611
TI  - Brain serotonin transporter binding in non-depressed patients with Parkinson's
      disease.
AB  - Early post-mortem data suggest that damage to brain serotonin neurones might play
      a role in some features (e.g., depression) of Parkinson's disease (PD). However,
      it is not known whether such damage is a typical characteristic of living
      patients with PD or whether the changes are regionally widespread. To address
      this question we measured, by positron emission tomography imaging, levels of the
      brain serotonin transporter (SERT), a marker for serotonin neurones, as inferred
      from binding of [11C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)
      benzonitrile (DASB), a second generation SERT radioligand, in subcortical and
      cerebral cortical brain areas of clinically advanced non-depressed (confirmed by
      structured psychiatric interview) patients with PD. SERT binding levels in PD
      were lower than those in controls in all examined brain areas, with the changes
      statistically significant in orbitofrontal cortex (-22%), caudate (-30%), putamen
      (-26%), and midbrain (-29%). However, only a slight non-significant reduction (
      7%) was observed in dorsolateral pre-frontal cortex, an area implicated in major
      depression. Our imaging data suggests that a modest, regionally widespread loss
      of brain serotonergic innervation might be a common feature of advanced PD.
      Further investigation will be required to establish whether SERT binding is more
      or less decreased in those patients with PD who also have major depressive
      disorder.

PMID- 17437613
TI  - High prevalence of restless legs syndrome in multiple sclerosis.
AB  - Despite the fact that multiple sclerosis (MS) patients often include leg
      restlessness as a sensory symptom, MS is not mentioned amongst symptomatic
      restless legs syndrome (RLS) forms. The aim of this study was to estimate RLS
      prevalence in a large population of MS patients, comparing clinical and MRI
      findings between patients with and without RLS. Each of the 156 MS patients (100
      females, 56 males, mean age 40.7 +/- 10.4) enrolled in a prospective study
      underwent a medical history interview, a neurological examination with the
      assessment of the Expanded Disability Status Scale (EDSS), and a structured
      questionnaire to verify the presence and features of RLS. Conventional brain
      spinal MRIs of 99 subjects were also evaluated and compared between patients with
      and without RLS. Fifty-one subjects (32.7%) (mean age 43.8 +/- 12.8) met the
      criteria for RLS. In a few patients (8.5%), the RLS preceded clinical MS onset,
      whilst in the remaining cases the RLS was followed by or was simultaneous with
      clinical MS onset. Comparing the RLS group with the group without RLS, no
      significant differences were found in MS duration, gender, and referred sleep
      habits. The primary progressive MS course was more represented in the RLS group,
      which also showed a higher EDSS score. RLS is a very common finding in MS
      patients and should be considered amongst the symptomatic RLS forms. RLS is also
      associated with higher disability.

PMID- 17437614
TI  - Cerebral blood flow in patients with diffuse axonal injury--examination of the
      easy Z-score imaging system utility.
AB  - To evaluate the utility of easy Z-score imaging system (eZIS) in 27 diffuse
      axonal injury (DAI) cases. Twenty-seven DAI patients were examined with an
      magnetic resonance imaging (MRI) T2* sequence and with eZIS (seven women, 20 men;
      age range, 19-35 years; median age: 26.6 years). In this investigation, we
      excluded patients who exhibited complications such as acute subdural hematoma,
      acute epidural hematoma, intracerebral hematoma, or brain contusion. We examined
      the neuropsychological tests and correlated with findings from MRI/eZIS.
      Furthermore, we evaluated the degree of ventricular enlargement in the bifrontal
      cerebroventricular index (CVI). Patients were divided into two groups: the
      enlargement group (bifrontal CVI > 35%, 12 patients) and the non-enlargement
      group (bifrontal CVI < 35%, 15 patients). All of the patients showed cognitive
      deficits as observed from the neuropsychological test results. Fifteen out of 27
      patients by MRI T1/T2 weighted images and fluid attenuated inversion recovery
      (FLAIR), 22 out of 27 patients by MRI T2* weighted images and 24 out of 27
      patients by eZIS showed abnormal findings. In MRI T2* weighted imaging, the white
      matter from the frontal lobe, corpus callosum, and brainstem showed abnormal
      findings. With eZIS, 22 patients (81.5%) showed blood flow degradation in the
      frontal lobe, and 12 patients (44.4%) in cingulate gyrus. In the enlargement
      group, Functional Independence Measure, Mini-Mental State Examination, Verbal IQ
      (VIQ)/Full Scale IQ (FIQ), Trail Making Test-B (TMT-B), and Non-paired of Miyake
      Paired Test were significantly lower. Amongst 12 patients without ventricular
      enlargement who had no abnormal findings in MRI T1/T2 weighted images and FLAIR,
      abnormal findings were detectable in seven patients with MRI T2* weighted imaging
      and to 10 patients with eZIS. Results of the MRI examination alone cannot fully
      explain DAI frontal lobe dysfunction. However, addition of the eZIS-assisted
      analysis derived from the single photon emission computed tomography (SPECT) data
      enabled us to understand regions where blood flow was decreased, i.e., where
      neuronal functions conceivably might be reduced.

PMID- 17437615
TI  - Relevant imaging findings of cerebral aspergillosis on MRI: a retrospective case
      based study in immunocompromised patients.
AB  - The aim of the study was to assess neuroimaging patterns of cerebral
      aspergillosis with magnetic resonance imaging (1.5 T). The clinical and imaging
      data of nine patients were reviewed. Patients were included in the study if the
      diagnosis of aspergillosis was confirmed by either biopsy, autopsy, aspergillus
      antigen determination and/or neuroradiological and clinical response to specific
      treatment. Four patients had single or multiple abscesses presenting as ring
      enhancing lesions on T1-weighted images, hypointensity of the ring on T2-weighted
      MR images and low to high signal intensity on diffusion-weighted imaging. Four
      patients had single or multiple infarctions affecting all compartments of the
      brain with hyperintensities on T2-weighted images in three of four patients,
      irregular parenchymal contrast enhancement in all patients and hemorrhagic
      transformation of the infarcted parenchyma in one patient. Diffusion-weighted
      images were positive in all ischemic areas. One patient with paranasal sinusitis
      developed a mycotic aneurysm of the internal carotid artery. Cerebral
      aspergillosis presents three principal neuroimaging findings: areas consistent
      with infarction; ring lesions consistent with abscess formation following
      infarction; and dural or vascular infiltration originating from paranasal
      sinusitis or orbital infiltration. Recognition of these patterns in cerebral
      aspergillosis may lead to more timely and effective diagnosis and treatment.

PMID- 17437616
TI  - The societal costs of intracerebral hemorrhage in Spain.
AB  - This study estimates the lifetime societal costs associated with incident
      intracerebral hemorrhage (ICH) in Spain. An epidemiological model of ICH
      incidence, survival and morbidity was developed using retrospective data from 28
      hospitals in Andalusia and published data identified in a systematic literature
      review. Data on resource utilization and costs were obtained from five hospitals
      in the Canary Islands, whereas cost of outpatient care, informal care and lost
      productivity were obtained from standardized questionnaires completed by
      survivors of ICH. The lifetime societal costs of incident ICH in Spain is
      estimated at 46,193 euros per patient. Direct medical costs accounted for 32.7%
      of lifetime costs, whilst 67.3% were related to indirect costs. One-third of
      direct medical costs over the first year were attributable to follow-up care,
      including rehabilitation. Indirect costs were dominated by costs of informal care
      (71.2%). The aggregated lifetime societal costs for the estimated 12,534 Spanish
      patients with a first-ever ICH in 2004 was 579 million euros. ICH implies
      substantial costs to society primarily due to formal and informal follow-up care
      and support needed after hospital discharge. Interventions that offer survival
      benefits without improving patients' functional status are likely to further
      increase the societal costs of ICH.

PMID- 17437617
TI  - Proteomic identification of potential protein markers in cerebrospinal fluid of
      GBS patients.
AB  - Increased protein level in the cerebrospinal fluid (CSF) is a characteristic of
      patients with Guillain-Barre syndrome (GBS), an acute inflammatory autoimmune
      disorder in the peripheral nervous system (PNS). However, the molecular
      mechanisms underlying the disease remain poorly understood and so far no reliable
      disease-related markers are available. By comparing the CSF proteome of GBS
      patients with control subjects suffering from other neurological disorders, it
      may be possible to identify proteins that involve in the disease process and thus
      to study the pathogenesis of GBS. We used two-dimensional difference gel
      electrophoresis (2D DIGE) technique, in combination with matrix-assisted laser
      desorption ionization time of flight mass spectrometry (MALDI-TOF MS), to
      determine the abnormal CSF proteins in GBS patients. Our data showed that the
      levels of six proteins and their isoforms in CSF were significantly altered in
      GBS patients compared with controls. Haptoglobin, apolipoprotein A-IV and PRO2044
      (unnamed protein) were considerably increased in the CSF of GBS patients, whereas
      transthyretin, apolipoprotein E and fibrinogen were considerably decreased. We
      concluded that these six proteins may be involved in the pathogenesis of GBS and
      call for further studying the role of these proteins in the pathogenesis of the
      disease.

PMID- 17437618
TI  - Episodic muscle pain, stiffness, and weakness associated with tubular aggregates
      and myoedema.
AB  - We report a 28-year-old man who suffered from episodic muscle pain, stiffness and
      weakness. His serum creatine kinase (CK) levels were found to be elevated. He
      presented with slight proximal muscle weakness and calf hypertrophy. Muscle
      biopsy revealed fiber size variation and tubular aggregates (TA). Muscle magnetic
      resonance imaging showed areas of edema. Other muscle pathologies known to be
      associated with TAs or myoedema were ruled out.

PMID- 17437619
TI  - Glutathione-S-transferase T1 and M1 gene polymorphisms in Greek patients with
      multiple sclerosis: a pilot study.
AB  - Oxidative stress has been implicated in the pathogenesis of multiple sclerosis
      (MS). Glutathione-S-transferases (GSTs) are detoxification enzymes, evolved to
      protect cells against reactive oxygen metabolites. Both GSTT1 and GSTM1 genes
      exhibit a homozygous deletion polymorphism (null genotype) leading to abolished
      enzyme activity. We studied the impact of the GSTT1 and GSTM1 polymorphisms on MS
      susceptibility in a case-control study of 47 Greek patients and 165 controls.
      Correlations between genotype, gender and disability status were also
      investigated. The incidence of both GSTT1 and GSTM1 genotypes did not differ
      significantly between controls and patients. A significantly increased frequency
      of GSTM1 null genotype was found amongst female patients (65.5%) as compared with
      males (33.3%, P =0.04). The results suggest that GSTT1 and GSTM1 have no major
      pathogenetic role on the MS occurrence, nor any strong modifying effect on the
      disability status. The higher incidence of GSTM1 null genotype observed in female
      patients, suggests a possible role of the GSTM1 detoxification pathway in a
      gender-dependent manner.

PMID- 17437620
TI  - Mitofusin 2 gene mutation (R94Q) causing severe early-onset axonal polyneuropathy
      (CMT2A).
AB  - Charcot-Marie-Tooth disease (CMT) has been classified into two types:
      demyelinating forms (CMT1) and axonal forms (CMT2). Mutations in the CMT2A locus
      have been linked to the KIF1B and the mitofusin 2 (MFN2) genes. Here, we report a
      German patient with CMT2 with an underlying spontaneous mutation (c.281G-->A) in
      the MFN2 gene. Clinically, the patient presented with early-onset CMT that was
      not associated with additional central nervous system pathology. The disease
      course was rapidly progressive in the first years and slowed afterwards. We also
      suggest that single patients with early-onset axonal polyneuropathies should be
      screened for MFN2 mutations.

PMID- 17437621
TI  - Intracranial dissemination of primary spinal cord anaplastic oligodendroglioma.
AB  - We report the first case of a 22-year-old man, with a previously neurosurgically
      treated intramedullary anaplastic oligodendroglioma (World Health Organization
      grade III), who developed 19 months later two histologically proven intracranial
      metastases. We support a hypothesis whereby the anaplastic parts of tumors have
      spread along the spinal cord and brainstem via the cerebrospinal fluid pathways,
      a process that could be promoted by surgical manipulation, although the relative
      contribution of the two factors remains speculative.

PMID- 17437622
TI  - Cognitive dysfunction and hypogonadotrophic hypogonadism in a Brazilian patient
      with mitochondrial neurogastrointestinal encephalomyopathy and a novel ECGF1
      mutation.
AB  - Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is caused by
      mutations in the thymidine phosphorylase gene (ECGF1). We present the first
      detailed report of a Brazilian MNGIE patient, harboring a novel ECGF1 homozygous
      mutation (C4202A, leading to a premature stop codon, S471X). Multiple deletions
      and the T5814C change were found in mitochondrial DNA. Together with
      gastrointestinal symptoms, endocrine involvement and memory dysfunction, not
      reported in MNGIE to date, were the most preeminent features.

PMID- 17437623
TI  - Post-ictal fever: a rare symptom of partial seizures.
AB  - Although fever may induce seizures, especially in children, its occurrence
      following epileptic spells has been rarely described, except from generalized
      convulsive status epilepticus. We present two patients suffering from focal
      seizures accompanied by episodes of post-ictal fever, and review similar reports
      in the literature of the last 40 years. Temperature changes following non
      convulsive seizures might be induced by gene upregulation occurring in the
      hypothalamus, the nucleus tractus solitarius, or in other brain regions,
      producing a local inflammatory response. Direct propagation of electrical
      discharges seems less consistent with the timing of development of this symptom.
      Heterogeneity of reported clinical features argues against the assumption of a
      definite localizing or lateralizing value for post-ictal fever.

PMID- 17437624
TI  - White matter changes in Leber's hereditary optic neuropathy: MRI findings.
AB  - Leber's hereditary optic neuropathy is a mitochondrial disorder causing bilateral
      optic nerve degeneration. It is sometimes associated with clinical signs of
      multiple sclerosis. We report MRI findings in two patients with LHON-MS and
      comment on possible distinguishing features of this disease entity.

PMID- 17437626
TI  - Decreased respiratory symptoms in cannabis users who vaporize.
AB  - Cannabis smoking can create respiratory problems. Vaporizers heat cannabis to
      release active cannabinoids, but remain cool enough to avoid the smoke and toxins
      associated with combustion. Vaporized cannabis should create fewer respiratory
      symptoms than smoked cannabis. We examined self-reported respiratory symptoms in
      participants who ranged in cigarette and cannabis use. Data from a large Internet
      sample revealed that the use of a vaporizer predicted fewer respiratory symptoms
      even when age, sex, cigarette smoking, and amount of cannabis used were taken
      into account. Age, sex, cigarettes, and amount of cannabis also had significant
      effects. The number of cigarettes smoked and amount of cannabis used interacted
      to create worse respiratory problems. A significant interaction revealed that the
      impact of a vaporizer was larger as the amount of cannabis used increased. These
      data suggest that the safety of cannabis can increase with the use of a
      vaporizer. Regular users of joints, blunts, pipes, and water pipes might decrease
      respiratory symptoms by switching to a vaporizer.

PMID- 17437625
TI  - Influence of oxygen on asexual blood cycle and susceptibility of Plasmodium
      falciparum to chloroquine: requirement of a standardized in vitro assay.
AB  - OBJECTIVE: The main objective of this study was to assess the influence of gas
      mixtures on in vitro Plasmodium falciparum growth and 50% inhibitory
      concentration (IC50) for chloroquine. METHODS: The study was performed between
      February 2004 and December 2005. 136 Plasmodium falciparum isolates were used to
      evaluate gas mixtures effect on IC50 for chloroquine by isotopic microtest. The
      oxygen effect on asexual blood cycle of 3D7 and W2 clones was determined by thin
      blood smears examination and tritiated hypoxanthine uptake. RESULTS: From 5% O2
      to 21% O2 conditions, no parasiticide effect of O2 concentration was observed in
      vitro on the clones 3D7 and W2. A parasitostatic effect was observed during the
      exposure of mature trophozoites and schizonts at 21% O2 with an increase in the
      length of schizogony. The chloroquine IC50 at 10% O2 were significantly higher
      than those at 21% O2, means of 173.5 nM and 121.5 nM respectively (p < 0.0001).
      In particular of interest, among the 63 isolates that were in vitro resistant to
      chloroquine (IC50 > 100 nM) at 10% O2, 17 were sensitive to chloroquine (IC50 <
      100 nM) at 21% O2. CONCLUSION: Based on these results, laboratories should use
      the same gas mixture to realize isotopic microtest. Further studies on comparison
      of isotopic and non-isotopic assays are needed to establish a standardized in
      vitro assay protocol to survey malaria drug resistance.

PMID- 17437627
TI  - Vanillin production using metabolically engineered Escherichia coli under non
      growing conditions.
AB  - BACKGROUND: Vanillin is one of the most important aromatic flavour compounds used
      in the food and cosmetic industries. Natural vanillin is extracted from vanilla
      beans and is relatively expensive. Moreover, the consumer demand for natural
      vanillin highly exceeds the amount of vanillin extracted by plant sources. This
      has led to the investigation of other routes to obtain this flavour such as the
      biotechnological production from ferulic acid. Studies concerning the use of
      engineered recombinant Escherichia coli cells as biocatalysts for vanillin
      production are described in the literature, but yield optimization and
      biotransformation conditions have not been investigated in details. RESULTS:
      Effect of plasmid copy number in metabolic engineering of E. coli for the
      synthesis of vanillin has been evaluated by the use of genes encoding feruloyl
      CoA synthetase and feruloyl hydratase/aldolase from Pseudomonas fluorescens BF13.
      The higher vanillin production yield was obtained using resting cells of E. coli
      strain JM109 harbouring a low-copy number vector and a promoter exhibiting a low
      activity to drive the expression of the catabolic genes. Optimization of the
      bioconversion of ferulic acid to vanillin was accomplished by a response surface
      methodology. The experimental conditions that allowed us to obtain high values
      for response functions were 3.3 mM ferulic acid and 4.5 g/L of biomass, with a
      yield of 70.6% and specific productivity of 5.9 micromoles/g x min after 3 hours
      of incubation. The final concentration of vanillin in the medium was increased up
      to 3.5 mM after a 6-hour incubation by sequential spiking of 1.1 mM ferulic acid.
      The resting cells could be reused up to four times maintaining the production
      yield levels over 50%, thus increasing three times the vanillin obtained per gram
      of biomass. CONCLUSION: Ferulic acid can be efficiently converted to vanillin,
      without accumulation of undesirable vanillin reduction/oxidation products, using
      E. coli JM109 cells expressing genes from the ferulic acid-degrader Pseudomonas
      fluorescens BF13. Optimization of culture conditions and bioconversion
      parameters, together with the reuse of the biomass, leaded to a final production
      of 2.52 g of vanillin per liter of culture, which is the highest found in the
      literature for recombinant strains and the highest achieved so far applying such
      strains under resting cells conditions.

PMID- 17437628
TI  - Attitudes towards terminal sedation: an empirical survey among experts in the
      field of medical ethics.
AB  - BACKGROUND: "Terminal sedation" regarded as the use of sedation in (pre-)terminal
      patients with treatment-refractory symptoms is controversially discussed not only
      within palliative medicine. While supporters consider terminal sedation as an
      indispensable palliative medical treatment option, opponents disapprove of it as
      "slow euthanasia". Against this background, we interviewed medical ethics experts
      by questionnaire on the term and the moral acceptance of terminal sedation in
      order to find out how they think about this topic. We were especially interested
      in whether experts with a professional medical and nursing background think
      differently about the topic than experts without this background. METHODS: The
      survey was carried out by questionnaire; beside the provided answering options
      free text comments were possible. As test persons we chose the 477 members of the
      German Academy for Ethics in Medicine, an interdisciplinary society for medical
      ethics. RESULTS: 281 completed questionnaires were returned (response rate =
      59%). The majority of persons without medical background regarded "terminal
      sedation" as an intentional elimination of consciousness until the patient's
      death occurs; persons with a medical background generally had a broader
      understanding of the term, including light or intermittent forms of sedation. 98%
      of the respondents regarded terminal sedation in dying patients with treatment
      refractory physical symptoms as acceptable. Situations in which the dying process
      has not yet started, in which untreatable mental symptoms are the indication for
      terminal sedation or in which life-sustaining measures are withdrawn during
      sedation were evaluated as morally difficult. CONCLUSION: The survey reveals a
      great need for research and discussion on the medical indication as well as on
      the moral evaluation of terminal sedation. Prerequisite for this is a more
      precise terminology which describes the circumstances of the sedation.

PMID- 17437629
TI  - Identification of a set of KSRP target transcripts upregulated by PI3K-AKT
      signaling.
AB  - BACKGROUND: KSRP is a AU-rich element (ARE) binding protein that causes decay of
      select sets of transcripts in different cell types. We have recently described
      that phosphatidylinositol 3-kinase/AKT (PI3K-AKT) activation induces
      stabilization and accumulation of the labile beta-catenin mRNA through an
      impairment of KSRP function. RESULTS: Aim of this study was to identify
      additional KSRP targets whose stability and steady-state levels are enhanced by
      PI3K-AKT activation. First, through microarray analyses of the AU-rich
      transcriptome in pituitary alphaT3-1 cells, we identified 34 ARE-containing
      transcripts upregulated in cells expressing a constitutively active form of AKT1.
      In parallel, by an affinity chromatography-based technique followed by microarray
      analyses, 12 mRNAs target of KSRP, additional to beta-catenin, were identified.
      Among them, seven mRNAs were upregulated in cells expressing activated AKT1. Both
      steady-state levels and stability of these new KSRP targets were consistently
      increased by either KSRP knock-down or PI3K-AKT activation. CONCLUSION: Our study
      identified a set of transcripts that are targets of KSRP and whose expression is
      increased by PI3K-AKT activation. These mRNAs encode RNA binding proteins,
      signaling molecules and a replication-independent histone. The increased
      expression of these gene products upon PI3K-AKT activation could play a role in
      the cellular events initiated by this signaling pathway.

PMID- 17437630
TI  - Development of a decision support tool to facilitate primary care management of
      patients with abnormal liver function tests without clinically apparent liver
      disease [HTA03/38/02]. Abnormal Liver Function Investigations Evaluation (ALFIE).
AB  - BACKGROUND: Liver function tests (LFTs) are routinely performed in primary care,
      and are often the gateway to further invasive and/or expensive investigations.
      Little is known of the consequences in people with an initial abnormal liver
      function (ALF) test in primary care and with no obvious liver disease. Further
      investigations may be dangerous for the patient and expensive for Health
      Services. The aims of this study are to determine the natural history of
      abnormalities in LFTs before overt liver disease presents in the population and
      identify those who require minimal further investigations with the potential for
      reduction in NHS costs. METHODS/DESIGN: A population-based retrospective cohort
      study will follow up all those who have had an incident liver function test (LFT)
      in primary care to subsequent liver disease or mortality over a period of 15
      years (approx. 2.3 million tests in 99,000 people). The study is set in Primary
      Care in the region of Tayside, Scotland (pop approx. 429,000) between 1989 and
      2003. The target population consists of patients with no recorded clinical signs
      or symptoms of liver disease and registered with a GP. The health technologies
      being assessed are LFTs, viral and auto-antibody tests, ultrasound, CT, MRI and
      liver biopsy. The study will utilise the Epidemiology of Liver Disease In Tayside
      (ELDIT) database to determine the outcomes of liver disease. These are based on
      hospital admission data (Scottish Morbidity Record 1), dispensed medication
      records, death certificates, and examination of medical records from Tayside
      hospitals. A sample of patients (n = 150) with recent initial ALF tests or
      invitation to biopsy will complete questionnaires to obtain quality of life data
      and anxiety measures. Cost-effectiveness and cost utility Markov model analyses
      will be performed from health service and patient perspectives using standard NHS
      costs. The findings will also be used to develop a computerised clinical decision
      support tool. DISCUSSION: The results of this study will be widely disseminated
      to primary care, as well as G.I. hospital specialists through publications and
      presentations at local and national meetings and the project website. This will
      facilitate optimal decision-making both for the benefit of the patient and the
      National Health Service.

PMID- 17437631
TI  - Sub-cellular localization and post-translational modifications of the Plasmodium
      yoelii enolase suggest moonlighting functions.
AB  - BACKGROUND: Enolase (2-Phospho-D-glycerate hydrolase; EC 4.2.1.11) is one of the
      glycolytic enzymes, whose levels are highly elevated in malaria parasite infected
      red blood cells. In several organisms, enolases have been shown to have diverse
      non glycolytic (moonlighting) biological functions. As functional diversity of a
      protein would require diverse sub-cellular localization, the possibility of
      involvement of Plasmodium enolase in moonlighting functions was examined by
      investigating its sub-cellular distribution in the murine malarial parasite,
      Plasmodium yoelii. METHODS: Cellular extracts of P. yoelii were fractionated in
      to soluble (cytosolic) and particulate (membranes, nuclear and cytoskeletal)
      fractions and were analysed by one and two-dimensional gel electrophoresis. These
      were probed by Western blotting using antibodies raised against recombinant
      Plasmodium falciparum enolase. Immunofluorescence assay was used for in situ
      localization. Fe+3 based metal affinity chromatography was used to isolate the
      phospho-proteome fraction from P. yoelii extracts. RESULTS: Apart from the
      expected presence of enolase in cytosol, this enzyme was also found to be
      associated with membranes, nuclei and cytoskeletal fractions. Nuclear presence
      was also confirmed by in situ immunofluorescence. Five different post
      translationally modified isoforms of enolase could be identified, of which at
      least three were due to the phosphorylation of the native form. in situ
      phosphorylation of enolase was also evident from the presence of enolase in
      purified phosphor-proteome of P. yoelii. Different sub-cellular fractions showed
      different isoform profiles. CONCLUSION: Association of enolase with nuclei, cell
      membranes and cytoskeletal elements suggests non-glycolytic functions for this
      enzyme in P. yoelii. Sub-cellular fraction specific isoform profiles indicate the
      importance of post-translational modifications in diverse localization of enolase
      in P. yoelii. Further, it is suggested that post-translational modifications of
      enolase may govern the recruitment of enolase for non-glycolytic functions.

PMID- 17437632
TI  - Chlamydia and gonorrhoea in pregnant Batswana women: time to discard the
      syndromic approach?
AB  - BACKGROUND: Chlamydia and gonorrhoea are major causes of morbidity among women in
      developing countries. Both infections have been associated with pregnancy-related
      complications, and case detection and treatment in pregnancy is essential. In
      countries without laboratory support, the diagnosis and treatment of cervical
      infections is based on the syndromic approach. In this study we measured the
      prevalence of chlamydia and gonorrhoea among antenatal care attendees in
      Botswana. We evaluated the syndromic approach for the detection of cervical
      infections in pregnancy, and determined if risk scores could improve the
      diagnostic accuracy. METHODS: In a cross-sectional study, 703 antenatal care
      attendees in Botswana were interviewed and examined, and specimens were collected
      for the identification of C trachomatis, N gonorrhoeae and other reproductive
      tract infections. Risk scores to identify attendees with cervical infections were
      computed based on identified risk factors, and their sensitivities,
      specificities, likelihood ratios and predictive values were calculated. RESULTS:
      The prevalence of chlamydia was 8%, and gonorrhoea was found in 3% of the
      attendees. Symptoms and signs of vaginal discharge did not predict cervical
      infection, and a syndromic approach failed to identify infected women. Age
      (youth) risk factor most strongly associated with cervical infection. A risk
      score with only sociodemographic factors had likelihood ratios equivalent to risk
      scores which incorporated clinical signs and microscopy results. However, all the
      evaluated risk scores were of limited value in the diagnosis of chlamydia and
      gonorrhoea. A cut-off set at an acceptable sensitivity to avoid infected
      antenatal care attendees who remained untreated would inevitably lead to
      considerable over-treatment. CONCLUSION: Although in extensive use, the syndromic
      approach is unsuitable for diagnosing cervical infections in antenatal care
      attendees in Botswana. None of the evaluated risk scores can replace this
      management. Without diagnostic tests, there are no adequate management strategies
      for C trachomatis and N gonorrhoeae in pregnant women in Botswana, a situation
      which is likely to apply to other countries in sub-Saharan Africa. Screening for
      cervical infections in pregnant women is an essential public health measure, and
      rapid tests will hopefully be available in developing countries within a few
      years.

PMID- 17437633
TI  - Cancer cell: using inflammation to invade the host.
AB  - BACKGROUND: Inflammation is increasingly recognized as an important component of
      tumorigenesis, although the mechanisms involved are not fully characterized. The
      invasive capacity of cancers is reflected in the classic metastatic cascade:
      tumor (T), node (N) and metastasis (M). However, this staging system for cancer
      would also have a tumoral biological significance. PRESENTATION OF THE
      HYPOTHESIS: To integrate the mechanisms that control the inflammatory response in
      the actual staging system of cancer. It is considered that in both processes of
      inflammation and cancer, three successive phenotypes are presented that represent
      the expression of trophic functional systems of increasing metabolic complexity
      for using oxygen. TESTING THE HYPOTHESIS: While a malignant tumor develops it
      express phenotypes that also share the inflammatory response such as: an ischemic
      phenotype (anoxic-hypoxic), a leukocytic phenotype with anaerobic glycolysis and
      migration, and an angiogenic phenotype with hyperactivity of glycolytic enzymes,
      tumor proliferation and metastasis, and cachexia of the host. The increasing
      metabolic complexity of the tumor cell to use oxygen allows for it to be
      released, migrate and proliferate, thus creating structures of growing
      complexity. IMPLICATION OF THE HYPOTHESIS: One aim of cancer gene therapy could
      be the induction of oxidative phosphorylation, the last metabolic step required
      by inflammation in order to differentiate the tissue that it produces.

PMID- 17437634
TI  - The innate immune repertoire in cnidaria--ancestral complexity and stochastic
      gene loss.
AB  - BACKGROUND: Characterization of the innate immune repertoire of extant cnidarians
      is of both fundamental and applied interest--it not only provides insights into
      the basic immunological 'tool kit' of the common ancestor of all animals, but is
      also likely to be important in understanding the global decline of coral reefs
      that is presently occurring. Recently, whole genome sequences became available
      for two cnidarians, Hydra magnipapillata and Nematostella vectensis, and large
      expressed sequence tag (EST) datasets are available for these and for the coral
      Acropora millepora. RESULTS: To better understand the basis of innate immunity in
      cnidarians, we scanned the available EST and genomic resources for some of the
      key components of the vertebrate innate immune repertoire, focusing on the
      Toll/Toll-like receptor (TLR) and complement pathways. A canonical Toll/TLR
      pathway is present in representatives of the basal cnidarian class Anthozoa, but
      neither a classic Toll/TLR receptor nor a conventional nuclear factor (NF)-kappaB
      could be identified in the anthozoan Hydra. Moreover, the detection of complement
      C3 and several membrane attack complex/perforin domain (MAC/PF) proteins suggests
      that a prototypic complement effector pathway may exist in anthozoans, but not in
      hydrozoans. Together with data for several other gene families, this implies that
      Hydra may have undergone substantial secondary gene loss during evolution. Such
      losses are not confined to Hydra, however, and at least one MAC/PF gene appears
      to have been lost from Nematostella. CONCLUSION: Consideration of these patterns
      of gene distribution underscores the likely significance of gene loss during
      animal evolution whilst indicating ancient origins for many components of the
      vertebrate innate immune system.

PMID- 17437635
TI  - Development of a one-step embryonic stem cell-based assay for the screening of
      sprouting angiogenesis.
AB  - BACKGROUND: Angiogenesis assays are important tools for the identification of
      regulatory molecules and the potential development of therapeutic strategies to
      modulate neovascularization. Although numerous in vitro angiogenesis models have
      been developed in the past, they exhibit limitations since they do not
      recapitulate the entire angiogenic process or correspond to multi-step procedures
      that are not easy to use. Convenient, reliable, easily quantifiable and
      physiologically relevant assays are still needed for pharmacological screenings
      of angiogenesis. RESULTS: Here, we have optimized an angiogenesis model based on
      ES cell differentiation for screening experiments. We have established conditions
      leading to angiogenic sprouting of embryoid bodies during ES cell differentiation
      in type I three-dimensional collagen gels. Immunostaining experiments carried out
      during these cultures showed the formation of numerous buds comprising CD31
      positive cells, after 11 days of culture of ES cells. Moreover, this one-step
      model has been validated in response to activators and inhibitors of
      angiogenesis. Sprouting was specifically stimulated in the presence of VEGF and
      FGF2. Alternatively, endothelial sprouting induced by angiogenic activators was
      inhibited by angiogenesis inhibitors such as angiostatin, TGFbeta and PF4.
      Sprouting angiogenesis can be easily quantified by image analysis after
      immunostaining of endothelial cells with CD31 pan-endothelial marker. CONCLUSION:
      Taken together, these data clearly validate that this one-step ES differentiation
      model constitutes a simple and versatile angiogenesis system that should
      facilitate, in future investigations, the screening of both activators and
      inhibitors of angiogenesis.

PMID- 17437636
TI  - Assessment of funnel plot asymmetry and publication bias in reproductive health
      meta-analyses: an analytic survey.
AB  - BACKGROUND: Despite efforts to assure high methodological standards, systematic
      reviews may be affected by publication bias. The objective of this study was to
      evaluate the occurrence of publication bias in a collection of high quality
      systematic reviews on reproductive health. METHODS: Systematic reviews included
      in the Reproductive Health Library (RHL), issue No 9, were assessed. Funnel plot
      was used to assess meta-analyses containing 10 or more trials reporting a binary
      outcome. A funnel plot, the estimated number of missing studies and the adjusted
      combined effect size were obtained using the "trim and fill method". Meta
      analyses results that were not considered to be robust due to a possible
      publication bias were submitted to a more detailed assessment. RESULTS: A total
      of 21 systematic reviews were assessed. The number of trials comprising each one
      ranged from 10 to 83 (median = 13), totaling 379 trials, whose results have been
      summarized. None of the reviews had reported any evaluation of publication bias
      or funnel plot asymmetry. Some degree of asymmetry in funnel plots was observed
      in 18 of the 21 meta-analyses evaluated (85.7%), with the estimated number of
      missing studies ranging from 1 to 18 (median = 3). Only for three meta-analyses,
      the conclusion could not be considered robust due to a possible publication bias.
      CONCLUSION: Asymmetry is a frequent finding in funnel plots of meta-analyses in
      reproductive health, but according to the present evaluation, less than 15% of
      meta-analyses report conclusions that would not be considered robust. Publication
      bias and other sources of asymmetry in funnel plots should be systematically
      addressed by reproductive health meta-analysts. Next amendments in Cochrane
      systematic reviews should include this type of evaluation. Further studies
      regarding the evolution of effect size and publication bias over time in
      systematic reviews in reproductive health are needed.

PMID- 17437637
TI  - Clofibrate treatment in pigs: effects on parameters critical with respect to
      peroxisome proliferator-induced hepatocarcinogenesis in rodents.
AB  - BACKGROUND: In rodents treatment with fibrates causes hepatocarcinogenesis,
      probably as a result of oxidative stress and an impaired balance between
      apoptosis and cell proliferation in the liver. There is some debate whether
      fibrates could also induce liver cancer in species not responsive to peroxisome
      proliferation. In this study the effect of clofibrate treatment on peroxisome
      proliferation, production of oxidative stress, gene expression of pro- and anti
      apoptotic genes and proto-oncogenes was investigated in the liver of pigs, a non
      proliferating species. RESULTS: Pigs treated with clofibrate had heavier livers
      (+16%), higher peroxisome counts (+61%), higher mRNA concentration of acyl-CoA
      oxidase (+66%), a higher activity of catalase (+41%) but lower concentrations of
      hydrogen peroxide (-32%) in the liver than control pigs (P < 0.05);
      concentrations of lipid peroxidation products (thiobarbituric acid-reactive
      substances, conjugated dienes) and total and reduced glutathione in the liver did
      not differ between both groups. Clofibrate treated pigs also had higher hepatic
      mRNA concentrations of bax and the proto-oncogenes c-myc and c-jun and a lower
      mRNA concentration of bcl-XL than control pigs (P < 0.05). CONCLUSION: The data
      of this study show that clofibrate treatment induces moderate peroxisome
      proliferation but does not cause oxidative stress in the liver of pigs. Gene
      expression analysis indicates that clofibrate treatment did not inhibit but
      rather stimulated apoptosis in the liver of these animals. It is also shown that
      clofibrate increases the expression of the proto-oncogenes c-myc and c-jun in the
      liver, an event which could be critical with respect to carcinogenesis. As the
      extent of peroxisome proliferation by clofibrate was similar to that observed in
      humans, the pig can be regarded as a useful model for investigating the effects
      of peroxisome proliferators on liver function and hepatocarcinogenesis.

PMID- 17437638
TI  - Does PGA external stenting reduce compliance mismatch in venous grafts?
AB  - BACKGROUND: Autogenous vein grafting is widely used in regular bypassing
      procedures. Due to its mismatch with the host artery in both mechanical property
      and geometry, the graft often over expands under high arterial blood pressure and
      forms a step-depth where eddy flow develops, thus causing restenosis, fibrous
      graft wall, etc. External stents, such as sheaths being used to cuff the graft,
      have been introduced to eliminate these mismatches and increase the patency.
      Although histological and immunochemical studies have shown some positive effects
      of the external stent, the mechanical mismatch under the protection of an
      external stent remains poorly analyzed. METHODS: In this study, the jugular veins
      taken from hypercholesterolemic rabbits were transplanted into the carotid
      arteries, and non-woven polyglycolic acid (PGA) fabric was used to fabricate the
      external stents to study the effect of the biodegradable external stent. Eight
      weeks after the operation, the grafts were harvested to perform mechanical tests
      and histological examinations. An arc tangent function was suggested to describe
      the relationship between pressure and cross-sectional area to analyse the
      compliance of the graft. RESULTS: The results from the mechanical tests indicated
      that grafts either with or without external stents displayed large compliance in
      the low-pressure range and were almost inextensible in the high-pressure range.
      This was very different from the behavior of the arteries or veins in vivo. The
      data from histological tests showed that, with external stents, collagen fibers
      were more compact, whilst those in the graft without protection were looser and
      thicker. No elastic fiber was found in either kind of grafts. Furthermore, grafts
      without protection were over-expanded which resulted in much bigger cross
      sectional areas. CONCLUSION: The PGA external extent contributes little to the
      reduction of the mechanical mismatch between the graft and its host artery while
      remodeling develops. For the geometric mismatch, it reduces the cross-section
      area, therefore matching with the host artery much better. Although there are
      some positive effects, conclusively the PGA is not an ideal material for external
      stent.

PMID- 17437639
TI  - Effects of curcumin on retinal oxidative stress and inflammation in diabetes.
AB  - BACKGROUND: Oxidative stress and inflammation are implicated in the pathogenesis
      of retinopathy in diabetes. The aim of this study is to examine the effect of
      curcumin, a polyphenol with antioxidant and anti-inflammatory properties, on
      diabetes-induced oxidative stress and inflammation in the retina of rats.
      METHODS: A group of streptozotocin-induced diabetic rats received powdered diet
      supplemented with 0.05% curcumin (w/w), and another group received diet without
      curcumin. The diets were initiated soon after induction of diabetes, and the rats
      were sacrificed 6 weeks after induction of diabetes. The retina was used to
      quantify oxidative stress and pro-inflammatory markers. RESULTS: Antioxidant
      capacity and the levels of intracellular antioxidant, GSH (reduced form of
      glutathione) levels were decreased by about 30-35%, and oxidatively modified DNA
      (8-OHdG) and nitrotyrosine were increased by 60-70% in the retina of diabetic
      rats. The levels of interleukin-1beta (IL-1beta) and vascular endothelial growth
      factor (VEGF) were elevated by 30% and 110% respectively, and the nuclear
      transcription factor (NF-kB) was activated by 2 fold. Curcumin administration
      prevented diabetes-induced decrease in the antioxidant capacity, and increase in
      8-OHdG and nitrotyrosine; however, it had only partial beneficial effect on
      retinal GSH. Curcumin also inhibited diabetes-induced elevation in the levels of
      IL-1beta, VEGF and NF-kB. The effects of curcumin were achieved without
      amelioration of the severity of hyperglycemia. CONCLUSION: Thus, the beneficial
      effects of curcumin on the metabolic abnormalities postulated to be important in
      the development of diabetic retinopathy suggest that curcumin could have
      potential benefits in inhibiting the development of retinopathy in diabetic
      patients.

PMID- 17437640
TI  - PRNP promoter polymorphisms are associated with BSE susceptibility in Swiss and
      German cattle.
AB  - BACKGROUND: Non-synonymous polymorphisms within the prion protein gene (PRNP)
      influence the susceptibility and incubation time for transmissible spongiform
      encephalopathies (TSE) in some species such as sheep and humans. In cattle, none
      of the known polymorphisms within the PRNP coding region has a major influence on
      susceptibility to bovine spongiform encephalopathy (BSE). Recently, however, we
      demonstrated an association between susceptibility to BSE and a 23 bp
      insertion/deletion (indel) polymorphism and a 12 bp indel polymorphism within the
      putative PRNP promoter region using 43 German BSE cases and 48 German control
      cattle. The objective of this study was to extend this work by including a larger
      number of BSE cases and control cattle of German and Swiss origin. RESULTS:
      Allele, genotype and haplotype frequencies of the two indel polymorphisms were
      determined in 449 BSE cattle and 431 unaffected cattle from Switzerland and
      Germany including all 43 German BSE and 16 German control animals from the
      original study. When breeds with similar allele and genotype distributions were
      compared, the 23 bp indel polymorphism again showed a significant association
      with susceptibility to BSE. However, some additional breed-specific allele and
      genotype distributions were identified, mainly related to the Brown breeds.
      CONCLUSION: Our study corroborated earlier findings that polymorphisms in the
      PRNP promoter region have an influence on susceptibility to BSE. However, breed
      specific differences exist that need to be accounted for when analyzing such
      data.

PMID- 17437641
TI  - An insight into the sialome of the oriental rat flea, Xenopsylla cheopis (Rots).
AB  - BACKGROUND: The salivary glands of hematophagous animals contain a complex
      cocktail that interferes with the host hemostasis and inflammation pathways, thus
      increasing feeding success. Fleas represent a relatively recent group of insects
      that evolved hematophagy independently of other insect orders. RESULTS: Analysis
      of the salivary transcriptome of the flea Xenopsylla cheopis, the vector of human
      plague, indicates that gene duplication events have led to a large expansion of a
      family of acidic phosphatases that are probably inactive, and to the expansion of
      the FS family of peptides that are unique to fleas. Several other unique
      polypeptides were also uncovered. Additionally, an apyrase-coding transcript of
      the CD39 family appears as the candidate for the salivary nucleotide hydrolysing
      activity in X.cheopis, the first time this family of proteins is found in any
      arthropod salivary transcriptome. CONCLUSION: Analysis of the salivary
      transcriptome of the flea X. cheopis revealed the unique pathways taken in the
      evolution of the salivary cocktail of fleas. Gene duplication events appear as an
      important driving force in the creation of salivary cocktails of blood feeding
      arthropods, as was observed with ticks and mosquitoes. Only five other flea
      salivary sequences exist at this time at NCBI, all from the cat flea C. felis.
      This work accordingly represents the only relatively extensive sialome
      description of any flea species. Sialotranscriptomes of additional flea genera
      will reveal the extent that these novel polypeptide families are common
      throughout the Siphonaptera.

PMID- 17437642
TI  - Possible role of the cavernous sinus veins in cerebrospinal fluid absorption.
AB  - The purpose of this investigation was to enhance our understanding of
      cerebrospinal fluid (CSF) absorption pathways. To achieve this, Microfil (a
      coloured silastic material) was infused into the subarachnoid space (cisterna
      magna) of sheep post mortem, and the relevant tissues examined macroscopically
      and microscopically. The Microfil was taken up by an extensive network of
      extracranial lymphatic vessels in the olfactory turbinates. In addition however,
      Microfil also passed consistently through the dura at the base of the brain.
      Microfil was noted in the spaces surrounding the venous network that comprises
      the cavernous sinus, in the adventitia of the internal carotid arteries and
      adjacent to the pituitary gland. Additionally, Microfil was observed within the
      endoneurial spaces of the trigeminal nerve and in lymphatic vessels emerging from
      the epineurium of the nerve. These results suggest several unconventional
      pathways by which CSF may be removed from the subarachnoid space. The movement of
      CSF to locations external to the cranium via these routes may lead to its
      absorption into veins and lymphatics outside of the skull. The physiological
      importance of these pathways requires further investigation.

PMID- 17437643
TI  - Prediction of flexible/rigid regions from protein sequences using k-spaced amino
      acid pairs.
AB  - BACKGROUND: Traditionally, it is believed that the native structure of a protein
      corresponds to a global minimum of its free energy. However, with the growing
      number of known tertiary (3D) protein structures, researchers have discovered
      that some proteins can alter their structures in response to a change in their
      surroundings or with the help of other proteins or ligands. Such structural
      shifts play a crucial role with respect to the protein function. To this end, we
      propose a machine learning method for the prediction of the flexible/rigid
      regions of proteins (referred to as FlexRP); the method is based on a novel
      sequence representation and feature selection. Knowledge of the flexible/rigid
      regions may provide insights into the protein folding process and the 3D
      structure prediction. RESULTS: The flexible/rigid regions were defined based on a
      dataset, which includes protein sequences that have multiple experimental
      structures, and which was previously used to study the structural conservation of
      proteins. Sequences drawn from this dataset were represented based on feature
      sets that were proposed in prior research, such as PSI-BLAST profiles,
      composition vector and binary sequence encoding, and a newly proposed
      representation based on frequencies of k-spaced amino acid pairs. These
      representations were processed by feature selection to reduce the dimensionality.
      Several machine learning methods for the prediction of flexible/rigid regions and
      two recently proposed methods for the prediction of conformational changes and
      unstructured regions were compared with the proposed method. The FlexRP method,
      which applies Logistic Regression and collocation-based representation with 95
      features, obtained 79.5% accuracy. The two runner-up methods, which apply the
      same sequence representation and Support Vector Machines (SVM) and Naive Bayes
      classifiers, obtained 79.2% and 78.4% accuracy, respectively. The remaining
      considered methods are characterized by accuracies below 70%. Finally, the Naive
      Bayes method is shown to provide the highest sensitivity for the prediction of
      flexible regions, while FlexRP and SVM give the highest sensitivity for rigid
      regions. CONCLUSION: A new sequence representation that uses k-spaced amino acid
      pairs is shown to be the most efficient in the prediction of the flexible/rigid
      regions of protein sequences. The proposed FlexRP method provides the highest
      prediction accuracy of about 80%. The experimental tests show that the FlexRP and
      SVM methods achieved high overall accuracy and the highest sensitivity for rigid
      regions, while the best quality of the predictions for flexible regions is
      achieved by the Naive Bayes method.

PMID- 17437644
TI  - The ability of natural tolerance to be applied to allogeneic tissue: determinants
      and limits.
AB  - BACKGROUND: Transplant rejection has been considered to occur primarily because
      donor antigens are not present during the development of the recipient's immune
      system to induce tolerance. Thus, transplantation prior to recipient immune
      system development (pre-immunocompetence transplants) should induce natural
      tolerance to the donor. Surprisingly, tolerance was often not the outcome in such
      'natural tolerance models'. We explored the ability of natural tolerance to
      prevent immune responses to alloantigens, and the reasons for the disparate
      outcomes of pre-immunocompetence transplants. RESULTS: We found that internal
      transplants mismatched for a single minor-H antigen and 'healed-in' before immune
      system development were not ignored but instead induced natural tolerance. In
      contrast, multiple minor-H or MHC mismatched transplants did not consistently
      induce natural tolerance unless they carried chimerism generating passenger
      lymphocytes. To determine whether the systemic nature of passenger lymphocytes
      was required for their tolerizing capacity, we generated a model of localized vs.
      systemic donor lymphocytes. We identified the peritoneal cavity as a site that
      protects allogeneic lymphocytes from killing by NK cells, and found that systemic
      chimerism, but not chimerism restricted to the peritoneum, was capable of
      generating natural tolerance. CONCLUSION: These data provide an explanation for
      the variable results with pre-immunocompetence transplants and suggest that
      natural tolerance to transplants is governed by the systemic vs. localized nature
      of donor antigen, the site of transplantation, and the antigenic disparity.
      Furthermore, in the absence of systemic lymphocyte chimerism the capacity to
      establish natural tolerance to allogeneic tissue appears strikingly limited.
      REVIEWERS: This article was reviewed by Matthias von Herrath, Irun Cohen, and Wei
      Ping Min (nominated by David Scott).

PMID- 17437646
TI  - A novel small molecule that selectively inhibits glioblastoma cells expressing
      EGFRvIII.
AB  - BACKGROUND: Mutations of the epidermal growth factor receptor (EGFR) are a
      possible molecular target for cancer therapy. EGFR is frequently amplified in
      glioblastomas and 30 to 40% of glioblastomas also express the deletion mutation
      EGFRvIII. This frequent oncogenic mutation provides an opportunity for
      identifying new anti-glioblastoma therapies. In this study, we sought small
      molecule inhibitors specific for cancer cells expressing EGFRvIII, using isogenic
      parental cells without EGFRvIII as a control. RESULTS: A screen of the NCI small
      molecule diversity set identified one compound, NSC-154829, which consistently
      inhibited growth of different human glioblastoma cells expressing EGFRvIII, but
      permitted normal growth of matched control cells. NSC-154829 had no previously
      established medicinal use, but has a purine-like structural component. Further
      experiments showed this compound increased apoptosis in cells with EGFRvIII, and
      moderately affected the expression of p21, independent of any changes in p53
      levels or in Akt phosphorylation. CONCLUSION: These initial results suggest that
      NSC-154829 or a closely related structure might be further investigated for its
      potential as an anti-glioblastoma drug, although its precise molecular mechanism
      is still undefined.

PMID- 17437645
TI  - Body mass index is associated with reduced exhaled nitric oxide and higher
      exhaled 8-isoprostanes in asthmatics.
AB  - BACKGROUND: Recently, it has been shown that increasing body mass index (BMI) in
      asthma is associated with reduced exhaled NO. Our objective in this study was to
      determine if the BMI-related changes in exhaled NO differ across asthmatics and
      controls, and to determine if these changes are related to increased airway
      oxidative stress and systemic levels of leptin and adiponectin. METHODS:
      Observational study of the association of BMI, leptin, and adiponectin with
      exhaled nitric oxide (NO) and exhaled 8-isoprostanes in 67 non-smoking patients
      with moderate to severe persistent asthma during baseline conditions and 47
      controls. Measurements included plasma levels of leptin, adiponectin, exhaled
      breath condensates for 8-isoprostanes, exhaled NO, pulmonary function tests, and
      questionnaires regarding asthma severity and control. RESULTS: In asthmatics, BMI
      and the ratio of leptin to adiponectin were respectively associated with reduced
      levels of exhaled NO (beta = -0.04 [95% C.I. -0.07, -0.1], p < 0.003) and (beta =
      -0.0018 [95% C.I. -0.003, -0.00034], p = 0.01) after adjusting for confounders.
      Also, BMI was associated with increased levels of exhaled 8-isoprostanes (beta =
      0.30 [95% C.I. 0.003, 0.6], p = 0.03) after adjusting for confounders. In
      contrast, we did not observe these associations in the control group of healthy
      non-asthmatics with a similar weight distribution. CONCLUSION: In adults with
      stable moderate to severe persistent asthma, but not in controls, BMI and the
      plasma ratio of leptin/adiponectin is associated with reduced exhaled NO. Also,
      BMI is associated with increased exhaled 8-isoprostanes. These results suggest
      that BMI in asthmatics may increase airway oxidative stress and could explain the
      BMI-related reductions in exhaled NO.

PMID- 17437647
TI  - Study of gene function based on spatial co-expression in a high-resolution mouse
      brain atlas.
AB  - BACKGROUND: The Allen Brain Atlas (ABA) project systematically profiles three
      dimensional high-resolution gene expression in postnatal mouse brains for
      thousands of genes. By unveiling gene behaviors at both the cellular and
      molecular levels, ABA is becoming a unique and comprehensive neuroscience data
      source for decoding enigmatic biological processes in the brain. Given the
      unprecedented volume and complexity of the in situ hybridization image data, data
      mining in this area is extremely challenging. Currently, the ABA database mainly
      serves as an online reference for visual inspection of individual genes; the
      underlying rich information of this large data set is yet to be explored by novel
      computational tools. In this proof-of-concept study, we studied the hypothesis
      that genes sharing similar three-dimensional expression profiles in the mouse
      brain are likely to share similar biological functions. RESULTS: In order to
      address the pattern comparison challenge when analyzing the ABA database, we
      developed a robust image filtering method, dubbed histogram-row-column (HRC)
      algorithm. We demonstrated how the HRC algorithm offers the sensitivity of
      identifying a manageable number of gene pairs based on automatic pattern
      searching from an original large brain image collection. This tool enables us to
      quickly identify genes of similar in situ hybridization patterns in a semi
      automatic fashion and consequently allows us to discover several gene expression
      patterns with expression neighborhoods containing genes of similar functional
      categories. CONCLUSION: Given a query brain image, HRC is a fully automated
      algorithm that is able to quickly mine vast number of brain images and identify a
      manageable subset of genes that potentially shares similar spatial co
      distribution patterns for further visual inspection. A three-dimensional in situ
      hybridization pattern, if statistically significant, could serve as a fingerprint
      of certain gene function. Databases such as ABA provide valuable data source for
      characterizing brain-related gene functions when armed with powerful image
      querying tools like HRC.

PMID- 17437650
TI  - Oral decontamination with chlorhexidine reduces the incidence of nosocomial
      pneumonia.

PMID- 17437651
TI  - Maxillary sinus haematoma.
AB  - The maxillary sinus haematoma is an uncommon cause of a maxillary sinus mass. It
      presents with a variety of symptoms, the most common being epistaxis. Although
      histologically benign, it may be clinically progressive. Radiological findings
      can range from a benign appearance to a more aggressive process, including bony
      erosion. Surgical evacuation is the mainstay of therapy. We describe our
      experience in managing this condition and review available literature on the
      subject.

PMID- 17437652
TI  - Jugular foramen meningocoele in a patient with neurofibromatosis type 1.
AB  - OBJECTIVE: We present a rare case of a jugular foramen meningocoele in a 48-year
      old female, with neurofibromatosis type 1, presenting with positional vertigo. We
      also postulate possible underlying pathophysiological mechanisms. METHOD: We
      describe the imaging findings of this rare entity and review the literature on
      skull base meningocoeles, particularly in the context of neurofibromatosis type
      1. RESULTS: A computed tomography scan revealed smooth expansion of the jugular
      foramen. Magnetic resonance imaging showed a fluid filled lesion expanding the
      jugular foramen and communicating with cerebrospinal fluid of the
      cerebellomedullary cistern superiorly. CONCLUSION: Skull base meningocoeles are a
      rare entity and we believe that this is the first reported case of a meningocoele
      causing enlargement of the jugular foramen in a patient with neurofibromatosis
      type 1. The meningocoele may have resulted from a severe form of dural ectasia or
      from dysplastic, weakened bone at the skull base.

PMID- 17437648
TI  - Evolutionary origins of insulin resistance: a behavioral switch hypothesis.
AB  - BACKGROUND: Insulin resistance, which can lead to a number of diseases including
      type 2 diabetes and coronary heart disease, is believed to have evolved as an
      adaptation to periodic starvation. The "thrifty gene" and "thrifty phenotype"
      hypotheses constitute the dominant paradigm for over four decades. With an
      increasing understanding of the diverse effects of impairment of the insulin
      signaling pathway, the existing hypotheses are proving inadequate. PRESENTATION
      OF THE HYPOTHESIS: We propose a hypothesis that insulin resistance is a socio
      ecological adaptation that mediates two phenotypic transitions, (i) a transition
      in reproductive strategy from "r" (large number of offspring with little
      investment in each) to "K" (smaller number of offspring with more investment in
      each) and (ii) a transition from "stronger to smarter" or "soldier to diplomat"
      i.e. from relatively more muscle dependent to brain dependent lifestyle. A common
      switch could have evolved for the two transitions since the appropriate
      environmental conditions for the two transitions are highly overlapping and
      interacting. TESTING THE HYPOTHESIS: Gestational insulin resistance diverts more
      energy through the placenta, resulting in increased investment per offspring. On
      the other hand, insulin resistance is associated with reduced ovulation. The
      insulin signaling pathway is also related to longevity. Insulin resistance
      diverts more nutrients to the brain as compared to muscle. Also, hyperinsulinemia
      has direct positive effects on cognitive functions of the brain. The hypothesis
      gets support from known patterns in human clinical data and recent research on
      the molecular interactions in the insulin signaling pathway. Further we state
      many predictions of the hypothesis that can be tested experimentally or
      epidemiologically. IMPLICATIONS OF THE HYPOTHESIS: The hypothesis can bring about
      a significant change in the line of treatment as well as public health policies
      for the control of metabolic syndrome.

PMID- 17437653
TI  - Differential neurotoxicity of tricyclic antidepressants and novel derivatives in
      vitro in a dorsal root ganglion cell culture model.
AB  - BACKGROUND AND OBJECTIVE: Tricyclic antidepressants are commonly employed orally
      to treat major depressive disorders and have been shown to be of substantial
      benefit in various chronic pain conditions. Among other properties they are
      potent Na+ channel blockers in vitro and show local anaesthetic properties in
      vivo. The present study aimed to determine their differential neurotoxicity, and
      that of novel derivatives as prerequisite for their potential use in regional
      anaesthesia. METHODS: To directly test neurotoxicity in adult peripheral neurons,
      the culture model of dissociated adult rat primary sensory neurons was employed.
      Neurons were incubated for 24 h with amitriptyline, N-methyl-amitriptyline,
      doxepin, N-methyl-doxepin, N-propyl-doxepin, desipramine, imipramine and
      trimipramine at 100 mumol, and at concentrations correlating to their respective
      potency in blocking sodium channels. RESULTS: All investigated substances showed
      considerable neurotoxic potency as represented in significantly decreased neuron
      numbers in cultures as compared to controls. Specifically, doxepin was more
      neurotoxic than amitriptyline, and both imipramine and trimipramine were more
      toxic than desipramine or amitriptyline. Novel derivatives of tricyclic
      antidepressants were, in general, more toxic than the parent compound.
      CONCLUSIONS: Tricyclic antidepressants and novel derivatives thereof show
      differential neurotoxic potential in vitro. The rank order of toxicity relative
      to sodium channel blocking potency was desipramine < amitriptyline < N-methyl
      amitriptyline < doxepin < trimipramine < imipramine < N-methyl doxepin < N-propyl
      doxepin.

PMID- 17437654
TI  - Effect of midazolam, dexamethasone and their combination on the prevention of
      nausea and vomiting following strabismus repair in children.
AB  - BACKGROUND: Postoperative nausea and vomiting is a common complication following
      strabismus surgery. This randomized and double-blind study was designed to
      evaluate the efficacy of midazolam alone or in combination with dexamethasone in
      reducing the incidence of postoperative nausea and vomiting in children
      undergoing strabismus repair. METHODS: One hundred ASA I children, aged 4-12 yr,
      scheduled to undergo elective strabismus surgery, were enrolled. No premedication
      was given. Anaesthesia was induced with sevoflurane, nitrous oxide and oxygen.
      After induction, fentanyl 2 microg kg-1 and cisatracurium 0.1 mg kg-1 were
      administered and an endotracheal tube was inserted. After induction of
      anaesthesia and before start of surgery, patients were randomly allocated into
      one of four groups of 25 children each to receive placebo, midazolam 50 microg kg
      1, dexamethasone 0.5 mg kg-1 or a combination of midazolam 50 microg kg-1 and
      dexamethasone 0.5 mg kg-1. Episodes of nausea, and retching and vomiting were
      recorded during the first 24 h after surgery. RESULTS: The incidence of
      postoperative nausea was 48%, 32%, 12% and 0% with placebo, dexamethasone,
      midazolam and the midazolam-dexamethasone combination, respectively. The
      incidence of vomiting was 52% and 32% with placebo and dexamethasone,
      respectively; no child vomited with midazolam alone, or with the midazolam
      dexamethasone combination. CONCLUSION: Prophylactic midazolam with or without
      dexamethasone reduces the incidence of PONV in children undergoing strabismus
      repair.

PMID- 17437656
TI  - Assessment of three different mortality prediction models in four well-defined
      critical care patient groups at two points in time: a prospective cohort study.
AB  - BACKGROUND AND OBJECTIVE: Mortality prediction systems have been calculated and
      validated from large mixed ICU populations. However, in daily practice it is
      often more important to know how a model performs in a patient subgroup at a
      specific ICU. Thus, we assessed the performance of three mortality prediction
      models in four well-defined patient groups in one centre. METHODS: A total of 960
      consecutive adult patients with either severe head injury (n = 299), multiple
      injuries (n = 208), abdominal aortic aneurysm (n = 267) or spontaneous
      subarachnoid haemorrhage (n = 186) were included. Calibration, discrimination and
      standardized mortality ratios were determined for Simplified Acute Physiology
      Score II, Mortality Probability Model II (at 0 and 24 h) and Injury Severity
      Score. Effective mortality was assessed at hospital discharge and after 1 yr.
      RESULTS: Eight hundred and fifty-five (89%) patients survived until hospital
      discharge. Over all four patient groups, Mortality Probability Model II (24 h)
      had the best predictive accuracy (standardized mortality ratio 0.62) and
      discrimination (area under the receiver operating characteristic curve 0.9), but
      Simplified Acute Physiology Score II performed well for patients with
      subarachnoid haemorrhage. Overall calibration was poor for all models (Hosmer
      Lemeshow Type C-values between 20 and 26). Injury Severity Score had the worst
      discrimination in trauma patients. All models over-estimated hospital mortality
      in all four patient groups, and these estimates were more like the mortality
      after 1 yr. CONCLUSIONS: In our surgical ICU, Mortality Probability Model II (24
      h) performed slightly better than Simplified Acute Physiology Score II in terms
      of overall mortality prediction and discrimination; Injury Severity Score was the
      worst model for mortality prediction in trauma patients.

PMID- 17437655
TI  - Ipsilateral shoulder pain after thoracotomy surgery: a prospective, randomized,
      double-blind, placebo-controlled evaluation of the efficacy of infiltrating the
      phrenic nerve with 0.2%wt/vol ropivacaine.
AB  - BACKGROUND: The aim of this prospective, randomized, double-blind, placebo
      controlled study was to evaluate the efficacy of phrenic nerve infiltration with
      ropivacaine 0.2% on the incidence and severity of ipsilateral shoulder pain after
      thoracotomy in patients receiving continuous thoracic epidural analgesia.
      METHODS: Fifty ASA physical status II-III patients, receiving thoracic epidural
      analgesia for post-thoracotomy pain, were randomly allocated to receive
      infiltration of the ipsilateral phrenic nerve with either ropivacaine 0.2% 10 mL
      (ropivacaine, n = 25), or saline 0.9% (control, n = 25) just before lung
      expansion and chest closure. A blinded observer recorded the incidence and
      severity of ipsilateral shoulder pain 6, 12, 24, 36 and 48 h after surgery.
      Postoperative respiratory function was also evaluated with blood gas analyses.
      RESULTS: The cumulative incidences of ipsilateral shoulder pain during the first
      24 h after surgery were 8/25 in the ropivacaine and 16/25 in the control groups
      (P = 0.047), with median (range) onset times for shoulder pain of 2 (2-24) h with
      ropivacaine and 0.5 (0.5-24) h in controls (P = 0.005). No differences were
      reported on the second postoperative day. The areas under the curves of the
      amount of pain over time were 0 (0-2760) mm h for the ropivacaine and 350 (0
      1900) mm h for the control groups (P = 0.06). Postoperatively, similar reductions
      in indices of oxygenation were observed in both groups. CONCLUSIONS: Phrenic
      nerve infiltration with ropivacaine 0.2% 10 mL reduced the incidence and delayed
      the onset of ipsilateral shoulder pain during the first 24 h after open lung
      resection, with no clinically relevant effects on respiratory function.

PMID- 17437657
TI  - Endogenous nitric oxide reduces the efficacy of the endothelin system to maintain
      blood pressure during high epidural anaesthesia in conscious dogs.
AB  - BACKGROUND AND OBJECTIVE: During high epidural anaesthesia, endothelin only
      contributes minimally to blood pressure stabilization. This phenomenon could
      result from the inhibitory action of nitric oxide on the endothelin system. To
      clarify this, we studied the interaction between nitric oxide and endothelin
      during high epidural anaesthesia in conscious dogs, in comparison to the
      interaction of nitric oxide and vasopressin. METHODS: Six animals were used in 45
      individual experiments randomly arranged as follows: N-omega-nitro-arginine
      methylester 0.3-10 mg kg-1 under physiological conditions or during high epidural
      anaesthesia (lidocaine 1%) and N-omega-nitro-arginine-methylester (l-NAME) 0.3-10
      mg kg-1 after preceding endothelin (Tezosentan(R)) or vasopressin (beta-mercapto
      beta,beta-cyclo-penta-methylene-propionyl-O-Me-Tyr-Arg-vasopressin) receptor
      blockade under physiological conditions or during high epidural anaesthesia.
      During control experiments normal saline was injected either intravenously (n =
      5) or into the epidural space (n = 4). RESULTS: N-omega-nitro-arginine
      methylester increased mean arterial pressure dose-dependently in all groups.
      However, this effect was substantially reduced in the presence of the endothelin
      receptor antagonist compared to N-omega-nitro-arginine-methylester alone, both
      under control conditions (7 +/- 3 vs. 21 +/- 3 mmHg; P < 0.05) and during high
      epidural anaesthesia (17 +/- 3 vs. 30 +/- 1 mmHg; P < 0.05). Blockade of
      vasopressin showed no similar relationship with N-omega-nitro-arginine
      methylester. CONCLUSIONS: The diminished increase in mean arterial pressure after
      injection of N-omega-nitro-arginine-methylester only during endothelin receptor
      blockade indicates that endogenous nitric oxide inhibits the action of endothelin
      during high epidural anaesthesia and might thus explain the reduced efficacy of
      endothelin in maintaining blood pressure during high epidural anaesthesia.

PMID- 17437658
TI  - Charter on continuing medical education/continuing professional development
      approved by the UEMS Specialist Section and European Board of Anaesthesiology.
AB  - The mission of the Section and Board of Anaesthesiology of the European Union of
      Medical Specialists (EUMS/UEMS) is to harmonize training and medical practice in
      all European countries to continuously improve the quality of care. The need for
      continuous medical education in the field of anaesthesiology has long been
      recognized. However, specialty-based competencies are not the only requirements
      for successful medical practice. The need to acquire medical, managerial,
      ethical, social and personal communication skills on top of specialty-based
      competencies has developed into the principle of continuous professional
      development, which embraces both objectives. The Section and Board of
      Anaesthesiology of the EUMS/UEMS has approved a proposal of its Standing
      Committee on Continuous Medical Education/Continuous Professional Development to
      adopt the following charter on the subject.

PMID- 17437659
TI  - Novel paradigm for treating vasculopathy in systemic sclerosis: vascular
      progenitor cells and statins.

PMID- 17437660
TI  - The molecular pathogenesis of Chlamydia-induced arthritis: where do we stand?

PMID- 17437661
TI  - Nitric oxide synthases and osteoarthritis.
AB  - The production of nitric oxide (NO) by chondrocytes is increased in human
      osteoarthritis. The excessive production of NO inhibits matrix synthesis and
      promotes its degradation. Furthermore, by reacting with oxidants such as
      superoxide anion, NO promotes cellular injury and renders the chondrocyte
      susceptible to cytokine-induced apoptosis. Thus, NO produced by activated
      chondrocytes in diseased cartilage may modulate disease progression in
      osteoarthritis and should therefore be considered a potential target for
      therapeutic intervention.

PMID- 17437662
TI  - Monitoring cartilage turnover.
AB  - In arthritic diseases, the stability of the extracellular matrix of articular
      cartilage is compromised by extensive proteolytic breakdown associated with
      alterations of synthesis of the proteins of the tissue leading to cartilage loss.
      This article reviews developments in assays of biochemical markers of cartilage
      matrix turnover and studies investigating their use. Because type II collagen and
      aggrecan are the most abundant proteins of the cartilage matrix, current
      biochemical markers are based mainly on immunologic reagents detecting their
      synthesis and degradation. Clinical studies indicate that some markers of type II
      collagen may be useful to predict disease progression in osteoarthritis and
      rheumatoid arthritis. Conversely, major achievements have been made in the
      development of immunoassays detecting the various fragments of aggrecan released
      by matrix metalloproteases or aggrecanases, but their use has been limited mostly
      to investigating cartilage turnover in ex vivo experiments. Because of the
      complexity of the mechanisms involved in arthritic joint damage, only a
      combination of different biochemical markers reflecting the various aspects of
      synthesis and degradation of matrix molecules will likely provide efficient
      cartilage turnover monitoring.

PMID- 17437663
TI  - The utility of nutraceuticals in the treatment of osteoarthritis.
AB  - Osteoarthritis (OA) treatment is limited by the inability of prescribed
      medications to alter disease outcome. As a result, patients with OA often take
      food substances called nutraceuticals in an attempt to affect the structural
      changes that occur within a degenerating joint. The role of nutraceuticals in OA
      management can be defined only by an evidence-based approach to support their
      use. This paper reviews the clinical trials studying glucosamine, chondroitin
      sulfate, vitamin C, vitamin E, and avocado-soybean unsaponifiables. It highlights
      the need for additional randomized, placebo-controlled trials to further define
      the utility of nutraceuticals in OA treatment.

PMID- 17437664
TI  - Treatment of osteoarthritis with anakinra.
AB  - Osteoarthritis (OA) is the most common form of arthritis and one of the leading
      causes of disability worldwide. The incidence of OA increases with age, and as
      longevity increases, it will cause a significant socioeconomic burden. No disease
      modifying therapy is available for OA. Recent research has highlighted the role
      of inflammation in the progression of OA. Interleukin-1 appears to have a
      significant role in disease progression. Since the interleukin-1 receptor
      antagonist (IL-1Ra) anakinra has been used successfully in the treatment of the
      inflammation and bone destruction of rheumatoid arthritis, some have suggested
      that it may be able to retard the disease progression of OA. This article reviews
      the data on the use of anakinra in OA treatment.

PMID- 17437666
TI  - Ibandronate injections in postmenopausal women with osteoporosis.

PMID- 17437665
TI  - Cardiovascular risk, hypertension, and NSAIDs.
AB  - During the past 2 years, a great deal of evaluation has been conducted on the
      cardiovascular (CV) effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and
      selective cyclooxygenase (COX)-2 inhibitors. This review focuses on the effects
      of the NSAIDs and COX-2 inhibitors on blood pressure and CV events. Clinical
      trial databases for NSAIDs and COX-2 inhibitors have shown varying levels of
      destabilization of blood pressure control in treated hypertensive patients as
      well as variable incident rates of the development of arrhythmias, congestive
      heart failure, myocardial infarction, and stroke. Nonselective and COX-2
      selective NSAIDs can be used carefully in arthritis patients with hypertension
      and stable CV disorders (excluding congestive heart failure and moderate to
      severe kidney dysfunction) when the individual clinical benefit of anti
      inflammatory therapy outweighs the CV and gastrointestinal risk.

PMID- 17437667
TI  - Denosumab in postmenopausal women with low bone mineral density.

PMID- 17437668
TI  - Cost-effectiveness modeling research of pharmacologic therapy to prevent
      osteoporosis-related fractures.
AB  - Osteoporotic fractures are common among postmenopausal women and elderly men, and
      they cause substantial direct medical costs and loss of quality of life. The
      potential costs of widespread intervention strategies to reduce the incidence of
      fractures are also quite high. Therefore, the cost-effectiveness of such
      interventions is highly significant to large-scale health insurers and healthcare
      systems. Most modeling studies to date have examined the cost-effectiveness of
      pharmacologic treatment for subsets of postmenopausal women selected on the basis
      of bone mineral density and/or prevalent vertebral fracture. They generally
      suggest that oral bisphosphonates and raloxifene are cost-effective therapies for
      these subsets. Increasingly, modeling studies of treatments for those selected on
      the basis of absolute fracture risk rather than bone density criteria are being
      done to establish absolute fracture risk thresholds at which various treatments
      are cost-effective.

PMID- 17437670
TI  - Absolute fracture risk.
AB  - Clinical evaluation of patients with low bone mass attempts to determine which
      patients should be offered one of the effective therapies for fracture
      prevention. Current guidelines are primarily based on bone density. Risk factors
      are used, but their contribution to fracture risk is not easily assessed. The
      combination of bone density and risk factors can be used to assess absolute
      fracture risk, the risk of fracture over a period of time expressed as a percent.
      This model will allow identification of patients who would benefit most from
      treatment.

PMID- 17437669
TI  - Kyphoplasty and vertebroplasty: how good is the evidence?
AB  - The absence of Level I evidence undermines the credibility of all clinical
      studies pertaining to percutaneous vertebral augmentation (ie, kyphoplasty and
      vertebroplasty). The powerful desire to relieve suffering in the frail elderly
      cannot substitute for a rigorously designed randomized controlled trial comparing
      vertebral augmentation with continued nonoperative care. Though the level of
      available evidence is currently inadequate, its quality is improving.

PMID- 17437671
TI  - Osteoporosis in men: pathophysiology and treatment.
AB  - Osteoporosis has long been long considered a disease of the aging female
      skeleton. However, it is now clear that men are also at risk for this disorder.
      Epidemiologic studies have confirmed that osteoporotic fractures in men are an
      increasing public health problem, in part due to increased longevity and
      increased public awareness. Recent large-scale population studies in men have led
      to advances in our understanding of bone fragility and its treatment in men. This
      article reviews what is known about the factors in men that lead to acquisition,
      maintenance, and loss of bone, as well as new insights into causes, pathogenesis,
      and treatment of osteoporosis in men.

PMID- 17437672
TI  - Emerging consensus on prevention and treatment of glucocorticoid-induced
      osteoporosis.
AB  - Glucocorticoid-induced osteoporosis is a common but still relatively neglected
      problem, with a low level of awareness among primary and secondary care
      physicians. Fractures appear early after initiation of treatment, and effective
      prophylaxis requires primary prevention in those at high risk of fracture.
      Bisphosphonates are the treatment of choice, and calcium and vitamin D
      supplements are also indicated in the majority of individuals. Organized care
      programs together with the use of evidence-based guidelines have the potential to
      improve significantly the management of this serious complication of
      glucocorticoid therapy.

PMID- 17437674
TI  - Revisiting the link between allergic rhinitis and asthma.

PMID- 17437673
TI  - Not just calcium and vitamin D: other nutritional considerations in osteoporosis.
AB  - Calcium and vitamin D are the mainstays of nutritional intervention for the
      prevention and treatment of osteoporosis. However, conditions that alter
      nutritional status as well as other nutrients should be considered when
      diagnosing and treating osteoporosis and osteopenia. Current research supports
      the early diagnosis and treatment of anorexia nervosa to prevent associated bone
      loss and increased risk of fracture. Weight restoration in patients with anorexia
      nervosa is central to bone mass stabilization. Other nutritional considerations
      include nutrients such as vitamin B-12 and vitamin K that may reduce fracture
      risk by increasing bone mineral density as well as the improvement of bone
      microarchitecture. Diets high in fruits and vegetables contribute nutrients such
      as magnesium associated with bone health and may also produce an alkaline
      environment, reducing calcium excretion and thus improving bone density.

PMID- 17437677
TI  - Sensing the air around us: the voltage-gated-like ion channel family.
AB  - Ion channels are a complex set of proteins having many important physiologic and
      potentially pathologic roles. The flow of ions through these channels and the
      subsequent cellular depolarization can trigger complex mechanisms such as cardiac
      rhythm, hormone secretion, and numerous sensory experiences. The transient
      receptor potential (TRP) channels are an important means for multiple organ
      systems to interact with their environment. The various TRP channel subfamilies
      respond to voltage or to ligands such as G-protein coupled receptors. Their
      ability to sense temperature, pain, stretch, and osmolarity among others enables
      them to mediate responses such as smooth muscle contraction, cough, or sensation
      of pain.

PMID- 17437679
TI  - The power of the placebo.
AB  - The placebo is much more than a control medicine in a clinical trial. The placebo
      response is the largest component of any allergy treatment and consists of two
      components: nonspecific effects (eg, natural recovery) and a "true placebo
      effect" that is the psychological therapeutic effect of the treatment. Belief in
      the beneficial nature of the treatment is a key component of the true placebo
      effect, and can be enhanced by factors such as interaction with the physician and
      the sensory impact of the treatment. Negative beliefs can generate a nocebo
      effect that may explain some psychogenic illnesses; this is the basis of much
      research in psychoneuroimmunology. An understanding of the placebo and nocebo
      effects is important for general allergy practice, and harnessing the power of
      the true placebo effect is a major challenge to modern medicine.

PMID- 17437678
TI  - Alpha and beta glucocorticoid receptors: relevance in airway diseases.
AB  - Glucocorticoids (GCs) are the most common and effective drugs for treating
      inflammatory airway respiratory diseases. Despite their efficacy, some patients
      respond poorly to GC treatment. Alterations in the expression of the receptor
      that mediates GC actions, the glucocorticoid receptor (GR), are one of the
      potential mechanisms that would explain GC insensitivity. In this review, we
      present an update on the GR gene and its products, namely GRalphaand GRbeta, as
      well as their alterations in disease. GRalpha has a widespread distribution and
      is responsible for the induction and repression of target genes, whereas GRbeta
      can act as a dominant negative inhibitor of GRalpha-mediated transactivation and
      transrepression. Very low GRbeta mRNA levels have been detected in a number of
      cells and tissues, which often contradict GRbeta protein data. Nevertheless, an
      association between GC insensitivity and increased GRbeta expression has been
      reported in asthma, nasal polyposis, and ulcerative colitis, and in vitro,
      certain pro-inflammatory cytokines upregulate GRbeta expression. However, the
      role of GRbeta in modulating GC sensitivity in vivo has been highly debated and
      is as yet unclear.

PMID- 17437680
TI  - Nasonasal reflexes, the nasal cycle, and sneeze.
AB  - The nasal mucosa is a complex tissue that interacts with its environment and
      effects local and systemic changes. Receptors in the nose receive signals from
      stimuli, and respond locally through afferent, nociceptive, type C neurons to
      elicit nasonasal reflex responses mediated via cholinergic neurons. This efferent
      limb leads to responses in the nose (eg, rhinorrhea, glandular hyperplasia,
      hypersecretion with mucosal swelling). Anticholinergic agents appear useful
      against this limb for symptomatic relief of a "runny nose." Chronic exposure to
      allergens can lead to hyperresponsiveness of the nasal mucosa. As a result,
      receptors upregulate specific ion channels to increase the sensitivity and
      potency of their reflex response. Nasal stimuli also affect distant parts of the
      body. Nerves in the sinus mucosa cause vasodilation; the lacrimal glands can be
      stimulated by nasal afferent triggers. Even the cardiopulmonary system can be
      affected via the trigeminal chemosensory system, where sensed irritants can lead
      to changes in tidal volume, respiratory rate, and blink frequency. The sneeze is
      an airway defense mechanism that removes irritants from the nasal epithelial
      surface. It is generally benign, but can lead to problems in certain
      circumstances. The afferent pathway involves histamine-mediated depolarization of
      H1 receptor-bearing type C trigeminal neurons and a complex coordination of
      reactions to effect a response.

PMID- 17437681
TI  - Nonallergic rhinitis in children.
AB  - Nonallergic rhinitis in children is a medical condition that has not been well
      defined and the true incidence is unknown. Current treatment recommendations are
      based on data obtained from adult studies. The mechanisms of pediatric
      nonallergic rhinitis are also unclear. The concept that laryngopharyngeal reflux
      (LPR) events may play a critical role in the pathogenesis of upper airway disease
      is presently under investigation. Although LPR is being better delineated and
      appropriate methods of diagnosis and treatment are being studied, substantial
      evidence links LPR with several disease states including rhinitis, sinus disease,
      and middle ear disease. Due to the lack of information concerning the etiology of
      nonallergic rhinitis in children, LPR should be considered in the differential
      diagnosis of a child with negative skin tests and chronic rhinitis symptoms. The
      clinician should especially give attention to this diagnosis when a child
      presents with recurrent co-morbid conditions such as chronic sinusitis or
      persistent middle ear disease.

PMID- 17437682
TI  - The way the wind blows: implications of modeling nasal airflow.
AB  - Nasal airflow is important for the many physiological functions of the nose,
      which include the warming and humidifying of inspired air; the filtration of
      airborne pollutants; and the sense of smell and nasal pungency. Until recently,
      airflow properties in the nose could only be understood using qualitative in
      vitro models of humans or in vivo studies in rodents. Recent advances in
      constructing three-dimensional geometric models of human nasal passages from CT
      scans, coupled with computational fluid dynamic modeling, has been a valuable
      tool for quantifying airflow and transport of gases, heat, particles, and
      aerosols in the human nose. Additionally, these techniques hold significant
      promise for evaluating and predicting the impact and successful remediation of a
      variety of clinical conditions on olfaction and nasal patency and setting
      guidelines for safe levels of exposure to inhaled materials.

PMID- 17437683
TI  - Leukotriene synthesis inhibitors versus antagonists: the pros and cons.
AB  - It has been recognized for many years that leukotrienes play an important role in
      mediating various effects of the allergic reaction. Recent evidence has shown
      that they play a role in other diseases. Leukotrienes can be separated into the
      fairly well-characterized cysteinyl leukotrienes and the less well-characterized
      leukotriene B(4). Effects of the leukotrienes are mediated through receptors that
      are expressed on a variety of cell types and can be modulated based on the
      inflammatory environment present. The pharmaceutical industry has long been
      interested in blocking leukotriene action. As such, two approaches have been
      developed that led to drugs approved for treating allergic disease. The most
      widely used class is the cysteinyl type 1 receptor antagonists, which block
      binding of the cysteinyl leukotrienes to the cell. The second class is an
      inhibitor of the 5-lipoxygenase enzyme that prevents synthesis of both the
      cysteinyl leukotrienes and leukotriene B(4). This review focuses on the role that
      leukotrienes play in various diseases, with the emphasis on allergic diseases,
      and considers the rationale for choosing either a leukotriene antagonist or
      synthesis inhibitor as a treatment option.

PMID- 17437684
TI  - Rodent models of allergic rhinitis: relevance to human pathophysiology.
AB  - Rodent models of allergic airways disease employ a wide range of test allergens,
      sensitization and provocation protocols, animal strains, and experimental
      endpoints. Studies of experimental asthma, especially the use of murine models,
      have contributed significantly to the understanding of the genetics and immune
      mediated pathophysiology of pulmonary airways during allergy. By comparison,
      rodent models of allergic rhinitis are less well developed. Recent interest in
      the potential mechanistic links between asthma and allergic rhinitis has
      increased the need for relevant animal studies directed at upper airways
      responses. Specifically, the nature of nasal airway remodeling in response to
      chronic activation of allergic pathways and its relationship to airway occlusion
      is not well described. This cursory review discusses current approaches to
      assessing nasal obstruction in rodent models, and how the histopathologic
      analysis might be improved to facilitate understanding of the pathogenesis of
      allergic rhinitis in humans.

PMID- 17437687
TI  - [Treatment of depression in children and adolescents].

PMID- 17437685
TI  - Are there reasons why adult asthma is more common in females?
AB  - Many epidemiological studies suggest that women are at increased risk of
      developing adult-onset asthma and also suffer from more severe disease than men.
      These gender differences appear to be the product of biological sex differences
      as well as sociocultural and environmental differences. The biological sex
      differences include genetic, pulmonary, and immunological factors. There is
      compelling evidence that sex hormones are major determinants of at least these
      biological sex differences. This paper explores the current literature regarding
      effects of sex hormones on immune function, resident lung cells, and regulation
      of local processes in the lung to shed light on underlying mechanisms of gender
      differences in asthma. More research is needed to understand these mechanisms in
      order to improve treatment of women with asthma.

PMID- 17437686
TI  - Tumor necrosis factor inhibitors for the treatment of asthma.
AB  - Asthma is a unique form of chronic airway inflammation characterized by
      reversible airway obstruction, airway hyperresponsiveness and the production of
      specific inflammatory mediators. Local activation of both immune and nonimmune
      cells in the lung triggers the release of these immunomodulator molecules. Among
      them, tumor necrosis factor (TNF)-alpha, a multipotent pro-inflammatory mediator,
      plays a critical role in immunoregulation of asthma by contributing to
      bronchopulmonary inflammation and airway hyperresponsiveness. Blocking TNF-alpha
      activity has already shown outstanding efficacy in other chronic inflammatory
      diseases including rheumatoid arthritis, Crohn's disease, and psoriasis. The
      successful treatment of these other chronic inflammatory diseases provides hope
      that TNF inhibitors may have application for the treatment of asthma. Recent
      developments in animal models and clinical trials in patients with severe asthma
      provide strong support for the concept that blocking TNF-alpha activity
      represents a new approach in asthma therapy. In this review, we address the
      multipotential role of TNF-alpha in asthma and the efficacy and safety of TNF
      alpha blocking agents in asthma.

PMID- 17437688
TI  - [Evidence for psychopharmacological treatment of depression in children and
      adolescents?].
AB  - Depression in children and adolescents is relatively prevalent and may have
      serious consequences. Treatment of depressive disorders may be psychotherapeutic
      or psychopharmacological. A systematic literature search was performed and the
      evidence for a psychopharmacological treatment of depressive disorders in
      children and adolescents was described. Emphasis is put on treatment with
      selective serotonin reuptake inhibitors as these are the best-documented agents
      in the treatment of depression in children and adolescents.

PMID- 17437689
TI  - [What evidence is there for treating depression in children and adolescents with
      cognitive therapy?].
AB  - Depression in children and adolescents is relatively prevalent and may have
      serious consequences. Treatment of depressive disorders may be psychotherapeutic
      or psychopharmacological. A systematic literature search was performed, and the
      evidence for treatment of depressive disorders in children and adolescents with
      cognitive behavioural therapy is described.

PMID- 17437691
TI  - [Ganglion--cysts of the hand and wrist].
AB  - Ganglion cysts of the hand and wrist occur most frequently during the second
      through fourth decade and women are more frequently affected than men. Ganglion
      cysts may arise in any location in the hand and wrist but are usually adjacent to
      joins or tendons and sometimes bones. Patients often present with a history of an
      asymptomatic mass and many patients seek the advice of a physician because of the
      cosmetic appearance of the cyst. Observation is acceptable in most instances.
      Indication for operative treatment includes pain, interference with activity,
      nerve compression and ulceration of the mucous cysts.

PMID- 17437690
TI  - [Vitamin D and breast cancer].
AB  - Active vitamin D increases the differentiation and exerts antiproliferative
      effects in cancer cells. Recent data suggest that vitamin D is activated locally
      in cancer cells. Ecologic studies have shown an inverse correlation between
      breast cancer mortality and sun exposure and dietary vitamin D intake. In
      clinical studies an impaired vitamin D status is associated with a 20-30%
      increased breast cancer incidence and 10-20% increased mortality. As vitamin D
      insufficiency is common, it is important to clarify whether vitamin D status
      affects the risk and prognosis of breast cancer.

PMID- 17437692
TI  - [Melatonin against surgical stress].
AB  - Surgery is associated with oxidative stress. Oxidative stress is correlated with
      postoperative myocardial ischaemia. It has been shown that the endogenous hormone
      melatonin has antioxidant effects. A potential benefit of melatonin has been
      proven in experimental studies as well as in neonates. Melatonin has not been
      used in adult patients with acute oxidative stress. A potential beneficial effect
      of melatonin in patients after surgery is possible and should be investigated in
      the future.

PMID- 17437693
TI  - [Anti-TNFalpha treatment of juvenile uveitis].
AB  - INTRODUCTION: To present our experience with anti-TNFalpha treatment of juvenile
      idiopatic arthritis (JIA) associated uveitis. MATERIALS AND METHODS: All 11
      children with severe uveitis were monitored between 2001 and 2005. Nine of the
      children had JIA and a set of twins had a rare hereditary granulomatous disease,
      Blau's syndrome. The patients were selected and the reason for starting anti
      TNFalpha treatment was an insufficient response in the arthritis or uveitis to
      previous therapy. RESULTS: In all patients the anti-TNFalpha treatment reduced
      the activity of uveitis. The response to treatment was related to 1) visual
      acuity and 2) the reduction of systemic immune-suppressing agents. All 11
      children are still on anti-TNFalpha treatment. CONCLUSION: Anti-TNFalpha was
      effective in treating uveitis in all 11 patients. In patients with active uveitis
      associated JIA not responding to corticosteroids and methotrexate and with
      declined vision the trend is to start anti-TNFalpha treatment early in the
      inflammatory disease to prevent long term complications to the eyes. The results
      indicate a superiority of infliximab over Eternacept in the treatment of uveitis.

PMID- 17437694
TI  - [Health economic consequences of the choice of follicle stimulating hormone
      alternatives in IVF treatment].
AB  - INTRODUCTION: There is a choice between two types of hormones for stimulation of
      the follicles in IVF treatment - recombinant FSH and the urine-derived
      menotrophin. A literature review by NICE (2004) in the United Kingdom documented
      that the two types of hormones were equally effective and safe, which is why it
      was recommended to use the cheaper urine-derived hormone. Based on the EISG study
      (European and Israeli Study Group), the aim was to analyse the health economic
      consequences of the choice between the two types of hormone in IVF treatment in
      Denmark. MATERIALS AND METHODS: In a prospective cost-effectiveness analysis
      (health care sector perspective), menotrophin and recombinant FSH (Gonal-F) were
      compared. Differences in costs were compared with differences in effects of the
      two alternatives. RESULTS: The total costs for the average patient are lower when
      using menotrophin compared with recombinant FSH. Furthermore, the cost per
      clinical pregnancy was lower with menotrophin compared with recombinant FSH
      hormone. Menotrophin is therefore less expensive both for the patient as well as
      for the health care sector. The use of menotrophin instead of recombinant FSH can
      result in savings of up to DKK 16 million on the drug budget--savings that could
      finance 1,400 additional IVF cycles. CONCLUSION: The analysis shows that urine
      derived menotrophin is a cost-effective alternative to recombinant FSH with a
      potential for considerable savings for patients as well as the public drug
      budget.

PMID- 17437695
TI  - [3-year follow-up of a child psychiatric cohort].
AB  - INTRODUCTION: Publications on prospective follow-up studies of Danish child
      psychiatric cohorts are scarce. Such studies are necessary in order to be able to
      inform patients about the natural course and prognosis of child psychiatric
      disorders. MATERIALS AND METHODS: Baseline data is obtained from 110 children,
      ie. 91 boys and 19 girls (4-13 years old) assessed in 2 child and adolescent
      psychiatric outpatient clinics in Denmark. As part of the baseline assessment,
      the children were clinically diagnosed and covered most of the child
      psychopathological spectrum. Baseline information included demographic data,
      assessment of symptom-load by means of The Child Behavior Checklist (CBCL) and a
      global function score. The children in the cohort were assessed once a year using
      the CBCL and the Teachers Report Form (TRF). RESULTS: The symptom-load is
      declining, although still high during the follow-up period. The decline in total
      behaviour problem scores was greater in the group of children diagnosed with
      emotional and behavioural disorders compared to those with neuropsychiatric
      disorders (Attention deficits and Autism spectrum disorders). CONCLUSION: In
      spite of the relatively small sample size, this follow-up study identifies
      important issues of prognostic value in this clinical child psychiatric
      outpatient population. The material may be useful as a 'treatment as usual' group
      in future clinical outcome studies.

PMID- 17437696
TI  - [250th anniversary of Rigets hospital. King Frederik's Hospital, the old and new
      Rigshospital].

PMID- 17437697
TI  - [Spontaneous hemothorax from a fibrous pleural tumour in an expectant father. Is
      the delivery room a dangerous place for men?].
AB  - A 34-year-old male was admitted to our department with dyspnoea and severe pain
      in the left hemithorax. The symptoms had started suddenly three days before in
      the delivery room when his child was being born. An X-ray of the chest showed a
      tumour in the left side of the mediastinum and a large left pleural effusion.
      This was confirmed by CT, which revealed a round mass 11 cm in diameter. During
      the operation a benign solitary fibrous tumour was radically resected from the
      pleura and a large hemothorax was removed. This unusual presentation with severe
      bleeding from a pleural tumour was most probably initiated by the expectant
      father's excitement during his wife's labour.

PMID- 17437698
TI  - [Autologous reconstruction with a femoral vein in cases of infection in synthetic
      prosthetic vascular grafts].
AB  - Infection in central prosthetic vascular grafts is a serious threat to both life
      and limb of the patient. Replacement of the infected material with autologous
      graft material is the logical treatment. Only recently, however, has it been
      demonstrated that it is possible to remove the patient's own femoral vein and use
      it as an arterial conduit. We report our initial experience with the first three
      operations performed in this country.

PMID- 17437699
TI  - Lightness and brightness.

PMID- 17437700
TI  - Global primary production.

PMID- 17437701
TI  - Aging without functional senescence in honey bee workers.

PMID- 17437702
TI  - Behaviour: begging is a joint effort in banded mongooses.
AB  - Lack of competition for food items in banded mongoose litters allows pups to
      benefit from more demanding siblings, suggesting that in this species begging may
      not be entirely selfish.

PMID- 17437703
TI  - Molecular motors: a tale of two filaments.
AB  - Cargos that are transported along actin frequently switch filaments. New work on
      single myosin V motors provides insight into this switching and its regulation,
      as well as revealing that myosin V diffuses on microtubules.

PMID- 17437704
TI  - PLK1 inhibitors: setting the mitotic death trap.
AB  - Polo-like kinase 1 (Plk1) regulates mitotic progression in all eukaryotes and has
      been implicated in the transformation of human cells. Analysis of the cytological
      and anti-tumor activities of BI 2536, a novel, selective pharmacological
      inhibitor of Plk1, has connected chemistry and biology to the bedside.

PMID- 17437705
TI  - Conservation ecology: area trumps mobility in fragment bird extinctions.
AB  - Tropical forest understory birds are highly sensitive to habitat fragmentation.
      Recent results from a monumental Amazonian fragmentation experiment show that
      habitat needs of these specialized birds make mobility a liability, leading to
      their extinctions from forest fragments.

PMID- 17437706
TI  - Cell death: hook, line and linker.
AB  - The programmed death of particular cells in Caenorhabditis elegans and Drosophila
      has been shown to occur by non-apoptotic programs regulated by developmental
      timing. Such alternative programs may be used as a general mechanism to eliminate
      differentiated, functional cells.

PMID- 17437707
TI  - Morphogenesis: joining the dots to shape an embryo.
AB  - In the study of morphogenesis, how upstream signalling events are intricately
      linked to downstream cytoskeletal organisation is not entirely understood. Recent
      work in the Drosophila embryo has begun to shed light on this problem.

PMID- 17437708
TI  - Circadian rhythms: per2bations in the liver clock.
AB  - A master circadian clock resides in the brain and is required to synchronize the
      clocks in peripheral tissues such as the liver. Until now, it has been unclear
      how the central clock synchronizes the peripheral ones. New work points to one of
      the core clock genes, mPer2, as an essential link in this chain.

PMID- 17437709
TI  - Aging: a young mind in old bees.
AB  - A new surprising study suggests that various cognitive abilities and motosensory
      functions remain perfectly intact as honeybee workers age. How do these findings
      fit in with a buzzing life?

PMID- 17437710
TI  - Human evolution: thrifty genes and the dairy queen.
AB  - Two new studies of genes that have experienced positive selection since the
      origin of pastoral agriculture help explain the incidence of lactose tolerance
      and diabetes, but cast considerable doubt on the popular thrifty genes
      hypothesis.

PMID- 17437711
TI  - A sliding restriction enzyme pauses.

PMID- 17437712
TI  - A left-handed RNA double helix bound by the Z alpha domain of the RNA-editing
      enzyme ADAR1.
AB  - The A form RNA double helix can be transformed to a left-handed helix, called Z
      RNA. Currently, little is known about the detailed structural features of Z-RNA
      or its involvement in cellular processes. The discovery that certain interferon
      response proteins have domains that can stabilize Z-RNA as well as Z-DNA opens
      the way for the study of Z-RNA. Here, we present the 2.25 A crystal structure of
      the Zalpha domain of the RNA-editing enzyme ADAR1 (double-stranded RNA adenosine
      deaminase) complexed to a dUr(CG)(3) duplex RNA. The Z-RNA helix is associated
      with a unique solvent pattern that distinguishes it from the otherwise similar
      conformation of Z-DNA. Based on the structure, we propose a model suggesting how
      differences in solvation lead to two types of Z-RNA structures. The interaction
      of Zalpha with Z-RNA demonstrates how the interferon-induced isoform of ADAR1
      could be targeted toward selected dsRNAs containing purine-pyrimidine repeats,
      possibly of viral origin.

PMID- 17437713
TI  - Functional differentiation of proteins: implications for structural genomics.
AB  - Structural genomics is a broad initiative of various centers aiming to provide
      complete coverage of protein structure space. Because it is not feasible to
      experimentally determine the structures of all proteins, it is generally agreed
      that the only viable strategy to achieve such coverage is to carefully select
      specific proteins (targets), determine their structure experimentally, and then
      use comparative modeling techniques to model the rest. Here we suggest that
      structural genomics centers refine the structure-driven approach in target
      selection by adopting function-based criteria. We suggest targeting functionally
      divergent superfamilies within a given structural fold so that each function
      receives a structural characterization. We have developed a method to do so, and
      an itemized survey of several functionally rich folds shows that they are only
      partially functionally characterized. We call upon structural genomics centers to
      consider this approach and upon computational biologists to further develop
      function-based targeting methods.

PMID- 17437714
TI  - Crystal structure of RNase T, an exoribonuclease involved in tRNA maturation and
      end turnover.
AB  - The 3' processing of most bacterial precursor tRNAs involves exonucleolytic
      trimming to yield a mature CCA end. This step is carried out by RNase T, a member
      of the large DEDD family of exonucleases. We report the crystal structures of
      RNase T from Escherichia coli and Pseudomonas aeruginosa, which show that this
      enzyme adopts an opposing dimeric arrangement, with the catalytic DEDD residues
      from one monomer closely juxtaposed with a large basic patch on the other
      monomer. This arrangement suggests that RNase T has to be dimeric for substrate
      specificity, and agrees very well with prior site-directed mutagenesis studies.
      The dimeric architecture of RNase T is very similar to the arrangement seen in
      oligoribonuclease, another bacterial DEDD family exoribonuclease. The catalytic
      residues in these two enzymes are organized very similarly to the catalytic
      domain of the third DEDD family exoribonuclease in E. coli, RNase D, which is
      monomeric.

PMID- 17437715
TI  - ATP ground- and transition states of bacterial enhancer binding AAA+ ATPases
      support complex formation with their target protein, sigma54.
AB  - Transcription initiation by the sigma54 form of bacterial RNA polymerase requires
      hydrolysis of ATP by an enhancer binding protein (EBP). We present SAS-based
      solution structures of the ATPase domain of the EBP NtrC1 from Aquifex aeolicus
      in different nucleotide states. Structures of apo protein and that bound to
      AMPPNP or ADP-BeF(x) (ground-state mimics), ADP-AlF(x) (a transition-state
      mimic), or ADP (product) show substantial changes in the position of the GAFTGA
      loops that contact polymerase, particularly upon conversion from the apo state to
      the ADP-BeF(x) state, and from the ADP-AlF(x) state to the ADP state. Binding of
      the ATP analogs stabilizes the oligomeric form of the ATPase and its binding to
      sigma54, with ADP-AlF(x) having the largest effect. These data indicate that ATP
      binding promotes a conformational change that stabilizes complexes between EBPs
      and sigma54, while subsequent hydrolysis and phosphate release drive the
      conformational change needed to open the polymerase/promoter complex.

PMID- 17437716
TI  - The dynamics of signal triggering in a gp130-receptor complex.
AB  - gp130 is a shared signal-transducing membrane-associated receptor for several
      hematopoietic cytokines. The 30 A resolution cryo-electron microscopy (cryo-EM)
      structure of the Interleukin 11(IL-11)-IL-11 Receptor-gp130 extracellular complex
      reveals the architecture and dynamics of this gp130-containing signaling complex.
      Normal-mode analysis reveals a repertoire of conformational changes that could
      function in signal triggering. This suggests a concerted mechanism of signaling
      involving all the components of the complex. This could provide a general
      mechanism of signal transfer for cytokines utilizing the JAK-STAT signaling
      cascade.

PMID- 17437717
TI  - BstYI bound to noncognate DNA reveals a "hemispecific" complex: implications for
      DNA scanning.
AB  - DNA recognition by proteins is essential for specific expression of genes in a
      living organism. En route to a target DNA site, a protein will often sample
      noncognate DNA sites through nonspecific protein-DNA interactions, resulting in a
      variety of conformationally different binding states. We present here the crystal
      structure of endonuclease BstYI bound to a noncognate DNA. Surprisingly, the
      structure reveals the enzyme in a "hemispecific" binding state on the pathway
      between nonspecific and specific recognition. A single base pair change in the
      DNA abolishes binding of only one monomer, with the second monomer bound
      specifically. We show that the enzyme binds essentially as a rigid body, and that
      one end of the DNA is accommodated loosely in the binding cleft while the other
      end is held tightly. Another intriguing feature of the structure is Ser172, which
      has a dual role in establishing nonspecific and specific contacts. Taken
      together, the structure provides a snapshot of an enzyme in a "paused"
      intermediate state that may be part of a more general mechanism of scanning DNA.

PMID- 17437718
TI  - Quasi-atomic model of bacteriophage t7 procapsid shell: insights into the
      structure and evolution of a basic fold.
AB  - The existence of similar folds among major structural subunits of viral capsids
      has shown unexpected evolutionary relationships suggesting common origins
      irrespective of the capsids' host life domain. Tailed bacteriophages are emerging
      as one such family, and we have studied the possible existence of the HK97-like
      fold in bacteriophage T7. The procapsid structure at approximately 10 A
      resolution was used to obtain a quasi-atomic model by fitting a homology model of
      the T7 capsid protein gp10 that was based on the atomic structure of the HK97
      capsid protein. A number of fold similarities, such as the fitting of domains A
      and P into the L-shaped procapsid subunit, are evident between both viral
      systems. A different feature is related to the presence of the amino-terminal
      domain of gp10 found at the inner surface of the capsid that might play an
      important role in the interaction of capsid and scaffolding proteins.

PMID- 17437719
TI  - NMR structural studies of the ItchWW3 domain reveal that phosphorylation at T30
      inhibits the interaction with PPxY-containing ligands.
AB  - In this work, we study the role of phosphorylation as a regulatory mechanism for
      the interaction between the E3 ubiquitin ligase ItchWW3 domain and two PPxY
      motifs of one of its targets, the Epstein-Barr virus latent membrane protein 2A.
      Whereas ligand phosphorylation only diminishes binding, domain phosphorylation at
      residue T30 abrogates it. We show that two ItchWW domains can be phosphorylated
      at this position, using CK2 and PKA kinases and/or with stimulated T lymphocyte
      lysates. To better understand the regulation process, we determined the NMR
      structures of the ItchWW3-PPxY complex and of the phosphoT30-ItchWW3 variant. The
      peptide binds the domain using both XP and tyrosine grooves. A hydrogen bond from
      T30 to the ligand is also detected. This hydrogen-bond formation is precluded in
      the variant, explaining the inhibition upon phosphorylation. Our results suggest
      that phosphorylation at position 30 in ItchWW domains can be a mechanism to
      inhibit target recognition in vivo.

PMID- 17437720
TI  - The structure of the C-terminal KH domains of KSRP reveals a noncanonical motif
      important for mRNA degradation.
AB  - The AU-rich element (ARE) RNA-binding protein KSRP (K-homology splicing regulator
      protein) contains four KH domains and promotes the degradation of specific mRNAs
      that encode proteins with functions in cellular proliferation and inflammatory
      response. The fourth KH domain (KH4) is essential for mRNA recognition and decay
      but requires the third KH domain (KH3) for its function. We show that KH3 and KH4
      behave as independent binding modules and can interact with different regions of
      the AU-rich RNA targets of KSRP. This provides KSRP with the structural
      flexibility needed to recognize a set of different targets in the context of
      their 3'UTR structural settings. Surprisingly, we find that KH4 binds to its
      target AREs with lower affinity than KH3 and that KSRP's mRNA binding, and mRNA
      degradation activities are closely associated with a conserved structural element
      of KH4.

PMID- 17437721
TI  - Structural basis for selective inhibition of Mycobacterium tuberculosis protein
      tyrosine phosphatase PtpB.
AB  - Tyrosine kinases and phosphatases establish the crucial balance of tyrosine
      phosphorylation in cellular signaling, but creating specific inhibitors of
      protein Tyr phosphatases (PTPs) remains a challenge. Here, we report the
      development of a potent, selective inhibitor of Mycobacterium tuberculosis PtpB,
      a bacterial PTP that is secreted into host cells where it disrupts unidentified
      signaling pathways. The inhibitor, (oxalylamino-methylene)-thiophene sulfonamide
      (OMTS), showed an IC(50) of 440 +/- 50 nM and >60-fold specificity for PtpB over
      six human PTPs. The 2 A resolution crystal structure of PtpB in complex with OMTS
      revealed a large rearrangement of the enzyme, with some residues shifting >27 A
      relative to the PtpB:PO(4) complex. Extensive contacts with the catalytic loop
      provide a potential basis for inhibitor selectivity. Two OMTS molecules bound
      adjacent to each other, raising the possibility of a second substrate
      phosphotyrosine binding site in PtpB. The PtpB:OMTS structure provides an
      unanticipated framework to guide inhibitor improvement.

PMID- 17437722
TI  - Comparison of three-year clinical outcome of sirolimus- and paclitaxel-eluting
      stents versus bare metal stents in patients with ST-segment elevation myocardial
      infarction (from the RESEARCH and T-SEARCH Registries).
AB  - Sirolimus-eluting stents (SESs) recently proved to be superior to bare metal
      stents (BMSs) in decreasing the need for repeat revascularization in patients
      with ST-segment elevation myocardial infarction (STEMI) at 1 year. Whether this
      also holds for paclitaxel-eluting stents (PESs) is currently unclear and the long
      term relatively efficacy of the 2 drug-eluting stents is currently unknown. We
      investigated the 3-year efficacy of SESs and PESs versus BMSs in patients with
      STEMI. Primary angioplasty was performed in a consecutive group of 505 patients
      (BMSs in 183, SESs in 186, PESs in 136). At 3 years, the cumulative mortality
      rate was comparable in the 3 groups: 13.3% in the BMS group, 11.5% in the SES
      group, and 12.4% in the PES group (nonsignificant for all). The rate of target
      vessel revascularization (TVR) was 12.0% in the BMS group compared with 8.0% and
      7.7% in the SES and PES groups, respectively (p = 0.12 for BMS vs SES, 0.30 for
      BMS vs PES, 0.62 for SES vs PES). The cumulative incidence of death, MI, or TVR
      was 25.5% in the BMS group compared with 17.9% and 20.6% in the SES and PES
      groups, respectively (p = 0.06 for BMS vs SES, 0.32 for BMS vs PES, 0.45 for SES
      vs PES). Angiographic stent thrombosis occurred in 2.4% of all patients (BMS
      1.6%, SES 2.7%, PES 2.9%). In conclusion, in this relatively small consecutive
      patient cohort, the use of SESs and PESs was no longer associated with
      significantly lower rates of TVR and major adverse cardiace events in patients
      with STEMI after 3 years of follow-up. A high frequency of stent thrombosis was
      observed in the 2 drug-eluting stent groups.

PMID- 17437723
TI  - Evaluation by optical coherence tomography of neointimal coverage of sirolimus
      eluting stent three months after implantation.
AB  - Confirming complete neointimal coverage after implantation of a drug-eluting
      stent is clinically important because incomplete stent coverage is responsible
      for late thrombosis and sudden cardiac death. Optical coherence tomography is a
      high-resolution (approximately 10 microm) imaging technique capable of detecting
      a thin layer of neointimal hyperplasia (NIH) inside a sirolimus-eluting stent
      (SES) and stent malapposition. This investigation evaluated stent exposure and
      malapposition 3 months after SES implantation using optical coherence tomography
      in a different clinical presentations, such as acute coronary syndrome (ACS) and
      non-ACS. Motorized optical coherence tomographic pullback (1 mm/s) was performed
      at 3-month follow-up to examine consecutive implanted 31 SESs in 21 lesions in 21
      patients (9 with ACS and 12 with non-ACS). NIH thickness inside each strut and
      percent NIH area in each cross section were measured. In total, 4,516 struts in
      567-mm single-stented segments were analyzed. Overall, NIH thickness and percent
      NIH area were 29 +/- 41 microm and 10 +/- 4%, respectively. Rates of exposed
      struts and exposed struts with malapposition were 15% and 6%, respectively. These
      were more frequent in patients with ACS than in those with non-ACS (18% vs 13%, p
      <0.0001; 8% vs 5%, p <0.005, respectively). In conclusion, neointimal coverage
      over a SES at 3-month follow-up is incomplete in ACS and non-ACS. Our study
      suggests that dual antiplatelet therapy might be continued >3 months after SES
      implantation.

PMID- 17437724
TI  - Analysis of 36 reported cases of late thrombosis in drug-eluting stents placed in
      coronary arteries.
AB  - Drug-eluting stents (DESs) have decreased the incidence of in-stent restenosis.
      Within the past 2 years several cases on late stent thrombosis (LST) have been
      reported. This study analyzed and reviewed all published cases of LST in DESs to
      explore possible trends not previously reported. We applied a Medline search
      using the key word "drug eluting stents." All 845 positive matches in March 2006
      were screened for case reports of LST in DESs, defined as angiographic stent
      thrombosis >or=30 days after deployment. We included reported LSTs from
      randomized trials, observational registry reports, and letters to the editor if
      information regarding timing from stent deployment to clinical event, vessel,
      stent diameter and length, and antiplatelet regimen were available. There was no
      significant difference in the incidence of LST between sirolimus- and paclitaxel
      eluting stents. Median time from stent deployment to clinical event was 242 days
      (total range 39 to 927). If aspirin and clopidogrel were discontinued, median
      time to clinical event was 7 days (3 to 150). In comparison, if only clopidogrel
      was discontinued, median time to clinical event was 30 days (14 to 690, p
      <0.0001). There was no significant difference in stent diameter and length
      between sirolimus- and paclitaxel-eluting stents. Forty-two percent of events
      occurred in relation to a surgical procedure for which the 2 antiplatelet agents
      or clopidogrel alone was discontinued. In conclusion, there was a strong
      association between occurrence of LST and cessation of dual antiplatelet therapy.
      Patients who continued on aspirin had a significant delay to the clinical event.
      Efforts should be made to maintain patients on aspirin during routine surgical
      procedures.

PMID- 17437725
TI  - Safety of sirolimus-eluting stenting and its effect on restenosis in patients
      with unstable angina pectoris (a SIRIUS substudy).
AB  - The SIRIUS study was a double-blinded, randomized trial of the sirolimus-eluting
      stent (SES) to evaluate its effect on the rate of restenosis. The present report
      is a retrospective analysis of short- and long-term outcomes of SESs compared
      with bare metal stents (BMSs) in a subgroup of patients with unstable angina
      enrolled in the trial. Of 1,058 patients randomized in SIRIUS, 533 (50.4%) had
      unstable angina pectoris and 490 had stable angina. In the unstable angina group,
      patients treated with SESs and BMSs had similar clinical and angiographic
      characteristics. The stenting procedure was highly successful in the 2 groups
      (95.9% and 97.4%, respectively) with similar immediate angiographic results and
      short-term (in-hospital) clinical event rates. At 1-year follow-up, compared with
      BMSs, patients with unstable angina treated with SESs had significantly lower
      rates of target lesion revascularization (5.5% vs 22.3%, p <0.0001), target
      vessel failure (10.9% vs 26.3%, p <0.0001), and major adverse cardiac events
      (8.4% vs 24.8%, p <0.0001). Stent thrombosis was a rare event, with only 1
      patient (0.4%) in each group during the first 30 days. Late thrombosis occurred
      in 2 patients (0.7%) in the BMS group but in none of the SES group. In
      conclusion, in the higher risk subgroup of patients with unstable angina, SESs
      are as safe as BMSs in decreasing restenosis and the need for repeat
      revascularization. This is reflected by a significant decrease in major adverse
      cardiac events and target vessel failure. Patients with unstable angina
      undergoing percutaneous coronary intervention who meet the entry criteria of the
      SIRIUS study should be preferentially treated with SESs.

PMID- 17437726
TI  - Usefulness of serum N-terminal pro-brain natriuretic peptide to predict in-stent
      restenosis in patients with preserved left ventricular function and normal
      troponin I levels.
AB  - The level of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a strong
      predictor of mortality in patients with acute coronary syndrome and may be a
      strong prognostic marker in patients with chronic coronary artery disease. We
      investigated whether NT-pro-BNP could predict in-stent restenosis (ISR) in
      asymptomatic patients with preserved left ventricular (LV) systolic function who
      underwent percutaneous coronary intervention. We measured serum NT-pro-BNP levels
      in 249 patients (61 +/- 9 years of age; 73% men) with preserved LV systolic
      function (ejection fraction >50%) who underwent follow-up coronary angiography.
      Initial diagnoses were stable angina in 50 (20%), unstable angina in 133 (53%),
      and myocardial infarction in 66 (27%). Baseline characteristics between groups
      with ISR (n = 92) and without ISR (n = 157) were similar. The level of NT-pro-BNP
      was higher in patients with ISR than in those without ISR (222 +/- 327 vs 94 +/-
      136 pg/ml, p = 0.001). In the ISR group, NT-pro-BNP level was higher in patients
      with left anterior descending coronary artery ISR (n = 53, 312 +/- 479 pg/ml)
      than in those with left circumflex coronary artery ISR (n = 19, 115 +/- 98 pg/ml,
      p = 0.018). At the standard cutoff of >200 pg/ml, a high NT-pro-BNP level
      indicated a high probability of ISR (odds ratio 2.18, 95% confidence interval 1.0
      to 4.5, p = 0.038). In multivariate analysis, NT-pro-BNP level was an independent
      predictor for ISR. In conclusion, NT-pro-BNP could be a predictor of ISR in
      asymptomatic patients with preserved LV systolic function.

PMID- 17437727
TI  - Impact of baseline platelet count in patients undergoing primary percutaneous
      coronary intervention in acute myocardial infarction (from the CADILLAC trial).
AB  - Despite the well-recognized role of platelets in the pathogenesis of acute
      myocardial infarction (AMI) and in the vascular responses to angioplasty, the
      relation between platelet count and outcomes after primary percutaneous coronary
      intervention (PCI) in AMI is unknown. We therefore determined the effect of
      baseline platelet count on clinical and angiographic outcomes of patients with
      AMI undergoing primary PCI. In the prospective, randomized CADILLAC trial,
      platelet count on admission was available in 2,021 of 2,082 patients (97.0%).
      Angiographic results and outcomes at 30 days and 1 year were stratified by
      quartiles of platelet count. Median platelet count was 231 x 10(9)/L (range 38 to
      709). Primary PCI angiographic success rates were independent of platelet count.
      The 30-day incidence of target vessel thrombosis or reocclusion increased
      steadily across the higher quartiles of baseline platelet count (0.2%, 0.6%,
      1.0%, and 2.0%, p = 0.027). At 1 year, patients with a baseline platelet count
      >or=234 versus <234 x 10(9)/L had higher rates of death or reinfarction (8.9% vs
      4.5%, p <0.0001), death (5.8% vs 3.1%, p = 0.002), and reinfarction (3.4% vs
      1.6%, p = 0.008). By multivariable analysis, a higher baseline platelet count was
      the strongest predictor of 1-year death or reinfarction (hazard ratio [HR] per
      10,000 increase in platelet count 1.02, 95% confidence interval [CI] 1.02 to
      1.07, p <0.0001) and independently predicted reinfarction (HR 1.06, 95% CI 1.02
      to 1.09, p = 0.002) and cardiac mortality (HR 1.03, 95% CI 1.00 to 1.06, p =
      0.055) at 1 year. In conclusion, a higher baseline platelet count in patients
      with AMI is a powerful independent predictor of death and reinfarction within the
      first year after primary PCI.

PMID- 17437728
TI  - Comparison of two antiplatelet regimens (aspirin alone versus aspirin +
      ticlopidine or clopidogrel) after intracoronary implantation of a carbofilm
      coated stent.
AB  - Stent thrombosis (ST) is an infrequent (0.5% to 1.5%) complication of
      intracoronary stenting, with severe clinical consequences. This multicenter,
      randomized study evaluated the clinical outcome in 479 patients (598 lesions
      treated) who underwent elective coronary stenting with a Carbofilm-coated stent
      (CarboStent) who met prespecified eligibility criteria and were randomly assigned
      to receive aspirin alone (n = 235) or aspirin plus a thienopyridine antiplatelet
      regimen (n = 244). Clinical, angiographic, and procedural characteristics were
      similar between groups. The primary end point was the incidence of 30-day ST;
      secondary end points included major vascular or bleeding complications within 30
      days and death, acute myocardial infarction, and target vessel revascularization
      at 6 months. ST occurred in 4 patients (1.4%) in the aspirin-only group and in 1
      patient (0.3%) in the aspirin-plus-thienopyridine group (relative risk 0.23, 95%
      confidence interval 0.03 to 2.08, p = NS). After careful review of cases, 89
      patients (19%) with protocol deviations were identified. When they were excluded
      from the analysis, no ST was observed in either group. Secondary end points were
      reached by 4% of the aspirin-alone group and 8% of the aspirin-plus
      thienopyridine group (relative risk 2.35, 95% confidence interval 0.94 to 5.85, p
      = NS). In conclusion, after optimal intracoronary implantation of the CarboStent,
      antiplatelet therapy with aspirin alone was safe and provided efficacy comparable
      to aspirin plus a thienopyridine in the prevention of ST.

PMID- 17437729
TI  - Relation between leucocyte count, myonecrosis, myocardial perfusion, and outcomes
      following primary angioplasty.
AB  - We examined whether leukocytosis is a negative prognostic factor in patients who
      underwent primary percutaneous coronary intervention (PCI) for acute myocardial
      infarction (AMI), and, if so, determined whether it is associated with impaired
      myocardial perfusion. Previous studies have identified leukocytosis as a
      predictor of mortality in AMI. Whether this association holds in patients how
      have undergone primary PCI using contemporary pharmacotherapy and correlates with
      impaired myocardial perfusion is unknown. Clinical outcomes and reperfusion
      success, using Thrombolysis In Myocardial Infarction (TIMI) flow and myocardial
      blush grades, were examined according to tertiles of baseline leukocyte count in
      1,268 patients who underwent primary PCI for AMI in the CADILLAC trial. Patients
      with higher leukocyte count were younger and more likely to be current smokers.
      Preprocedure TIMI grade 0 flow was more frequent in patients with higher
      leukocyte counts, but postprocedural TIMI grade 3 flow rates were equally high
      (>94%) in all 3 groups. Myocardial blush grade 2/3 was achieved at similar rates
      after PCI in patients with low, intermediate, and high baseline leukocyte counts
      (52.0% vs 51.5% vs 50.1%, p = 0.8). Higher baseline leukocyte counts were
      associated with greater myonecrosis (p <0.0001) and increased mortality at 1 year
      (2.7% vs 4.6% vs 5.4%, respectively, p = 0.047). By multivariate analysis,
      baseline leukocyte count (in increments of 1,000, hazard ratio 1.07, 95%
      confidence interval 1.02 to 1.10, p = 0.005) and peak creatine phosphokinase
      (hazard ratio 1.22, 95% confidence interval 1.14 to 1.29, p <0.001) were
      independent predictors of 1-year mortality. In conclusion, baseline leukocytosis
      is an independent correlate of larger infarct and increased mortality after
      primary PCI in AMI, an effect not explained by decreased myocardial perfusion.

PMID- 17437730
TI  - Cyphering the complexity of coronary artery disease using the syntax score to
      predict clinical outcome in patients with three-vessel lumen obstruction
      undergoing percutaneous coronary intervention.
AB  - The Syntax score (SXscore) was recently developed as a comprehensive angiographic
      scoring system aiming to assist in patient selection and risk stratification of
      patients with extensive coronary artery disease undergoing contemporary
      revascularization. A validation of this angiographic classification scheme is
      lacking. We assessed its predictive value in patients who underwent percutaneous
      intervention (PCI) for 3-vessel disease and explored its performance in
      comparison with the modified lesion classification system of the American Heart
      Association/American College of Cardiology. The SXscore, applied to 1,292 lesions
      in 306 patients who underwent PCI for 3-vessel disease in the Arterial
      Revascularization Therapies Study Part II, was 4 to 54.5, and after a median of
      370 days (range 274 to 400) predicted the rate of major adverse cardiac and
      cerebrovascular events (hazard ratio 1.08/U increase, 95% confidence interval
      1.05 to 1.11, p <0.0001), with patients in the highest SXscore tertile having a
      significantly higher event rate (27.9%) than patients in the lowest tertile
      (8.7%, hazard ratio 3.5, 95% confidence interval 1.7 to 7.4, p = 0.001). By
      multivariable analyses, SXscore independently predicted outcome with an almost
      fourfold adjusted increase in the risk of major adverse cardiac and
      cerebrovascular events in patients with high versus low values based on the
      discrimination level provided by classification and regression tree analysis.
      Compared with the modified lesion classification scheme of the American Heart
      Association/American College of Cardiology, SXscore showed a greater
      discrimination ability (c-index 0.58 +/- 0.08 vs 0.67 +/- 0.08, respectively, p
      <0.001) and a better goodness of fit with the Hosmer-Lemeshow statistic. In
      conclusion, the SXscore is a promising tool to risk stratify outcome in patients
      with extensive coronary artery disease undergoing contemporary PCI.

PMID- 17437731
TI  - Comparison of efficacy and safety of lower-dose to higher-dose oral prednisone
      after percutaneous coronary interventions (the IMPRESS-LD study).
AB  - This study assessed clinical and angiographic efficacies of oral treatment with
      prednisone at low-dose (LD) versus the previous high-dose (HD) immunosuppressive
      dosage used after percutaneous coronary interventions (PCIs) with bare metal
      stents in patients with multivessel coronary artery disease. Forty-three patients
      with multivessel disease successfully treated with multiple PCIs were matched to
      the previous HD IMPRESS-2/MVD study population. The 43 patients were treated for
      103 coronary stenoses and received 30-day oral prednisone treatment (LD group 1
      mg/kg for 5 days, 0.5 mg/kg for 10 days, 0.25 mg/kg for 15 days) and were
      compared retrospectively with the 43 patients in the HD IMPRESS-2/MVD study with
      116 treated coronary lesions (HD group 1 mg/kg for 10 days, 0.5 mg/kg for 20
      days, 0.25 mg/kg for 15 days). The primary clinical end point was 12-month event
      free survival rate (defined as freedom from death, myocardial infarction, and
      need for target vessel revascularization). The secondary end point was
      angiographic restenosis at 8 months assessed by quantitative coronary
      angiography. Event-free survival rates were 74% and 93% in the LD and HD groups,
      respectively (relative risk 4.6, 95% confidence interval 1.18 to 17.8, p =
      0.019). Restenosis was observed in 4 lesions (4%) in the HD group and in 20
      lesions (22%) in the LD group (p <0.001). Mean late lumen loss was 0.61 +/- 0.35
      mm, and the loss index was 31.3 +/- 21.6% in the HD group compared with 0.87 +/-
      0.61 mm and 52.03 +/- 25.1% in the LD group (p = 0.03 and 0.02, respectively). In
      conclusion, antirestenotic efficacy of oral treatment with prednisone after
      conventional PCI is dose sensitive. A 50% dose decrease in oral prednisone, as
      tested in this study, is less effective than the previously tested HD IMPRESS
      therapeutic scheme.

PMID- 17437732
TI  - Relation of polymorphisms in five genes to long-term aortocoronary saphenous vein
      graft patency.
AB  - Saphenous veins grafts (SVGs) continue to be used as conduits for coronary bypass
      surgery in nearly 350,000 patients annually in the United States. A possible
      genetic contribution to SVG longevity has not been well studied. We analyzed 168
      single nucleotide polymorphisms from 150 candidate genes in 155 patients (2.1
      SVGs/patient) followed for 10 +/- 4 years who underwent coronary angiography for
      clinical indications. Age at coronary bypass was 54 +/- 8 years, 61% were men,
      and 39% had diabetes mellitus. At the time of study entry, 76% were on statins.
      SVG patency (<70% diameter stenosis, no intervention), the primary study end
      point, was 60% at 5 years and 19% at 10 years. After adjustment for other factors
      associated with SVG patency (male gender, p = 0.007; low low-density lipoprotein,
      p = 0.016), 7 polymorphisms in 5 genes were associated with SVG patency (p
      <0.01). In conclusion, these data represent an initial step toward the use of a
      personalized genetic approach to coronary revascularization.

PMID- 17437733
TI  - Comparison of magnetic resonance perfusion imaging versus invasive fractional
      flow reserve for assessment of the hemodynamic significance of epicardial
      coronary artery stenosis.
AB  - This study evaluated whether first-pass perfusion cardiovascular magnetic
      resonance (FP-CMR) could predict the hemodynamic significance of epicardial
      coronary artery stenosis as defined by invasively determined fractional flow
      reserve at coronary angiography. In 19 patients with known coronary artery
      disease (CAD), the hemodynamic relevance of 22 stenoses (mean angiographic
      severity 73 +/- 9%) was determined using fractional flow reserve measurements
      (cutoff 0.75). Results were compared with a territorial index of myocardial
      perfusion reserve (MPR) derived from FP-CMR. In addition, 9 age-matched patients
      with low prevalence of risk factors and without CAD at angiography served as a
      control group. A cutoff of 1.5 for MPR separated hemodynamically relevant from
      nonrelevant stenoses with a sensitivity and specificity of 92% and 92%,
      respectively. The area under the receiver-operator characteristic curve was 0.97.
      In the patient group, territories supplied by arteries without significant
      stenosis (<or=50%) showed a lower MPR compared with the control group (p
      <0.0001), suggesting the presence of microvascular dysfunction. In conclusion, FP
      CMR may be useful for assessment of the hemodynamic relevance of angiographically
      undetermined CAD.

PMID- 17437734
TI  - Value of electrocardiographically gated single-photon emission computed
      tomographic myocardial perfusion scintigraphy in a cohort of symptomatic
      postmenopausal women.
AB  - The aim of this study is to prospectively evaluate the clinical value of
      electrocardiographically gated single-photon emission computed tomographic
      myocardial perfusion scintigraphy (MPS) imaging in a cohort of postmenopausal
      women with symptoms suggestive of ischemic heart disease. Forty-six
      postmenopausal women with no history of coronary artery disease (CAD), but with
      typical or atypical angina and >or=1 risk factor for CAD, were enrolled and
      underwent both coronary angiography and technetium-99m sestamibi MPS with
      exercise (n = 36) or pharmacologic stress (n = 10). All women were followed up
      for 5.0 +/- 3 years for the occurrence of hospitalization for acute coronary
      syndrome, myocardial infarction, and/or new-onset or worsening angina. CAD
      prevalence (>or=50% diameter stenosis) was 62% (26 of 42 patients). Fifteen
      patients (36%) had 1-vessel disease, 7 (17%) had 2-vessel disease, and 4 (10%)
      had 3-vessel disease. Diagnostic sensitivity and specificity of the exercise
      electrocardiogram were 67% and 69%, respectively. By comparison, sensitivity of
      MPS was 88% and specificity was 87.5% (p <0.0001). Cox survival analysis showed 3
      and 5-year cumulative event-free survival rates of 97% and 94% for patients with
      normal MPS results compared with 60% and 48% for those with abnormal MPS findings
      (p <0.001). In conclusion, results of this study indicate high diagnostic and
      prognostic accuracy for MPS in symptomatic postmenopausal women.

PMID- 17437735
TI  - Polymorphisms in the paraoxonase and endothelial nitric oxide synthase genes and
      the risk of early-onset myocardial infarction.
AB  - In young patients, the accumulative burden of traditional cardiovascular risk
      factors may not be as significant as in an older population. Genetic risk factors
      were suggested to have a role in the early development of myocardial infarction
      (MI). However, data about the association between polymorphisms in heart disease
      related genes and the early onset of a first MI are limited. In the present
      study, age at onset of a first MI was related to individual single-nucleotide
      polymorphisms in each of 18 prespecified candidate genes in a cohort of 814
      patients enrolled in the Thrombogenic Factors and Recurrent Coronary Events
      (THROMBO) Study. Multivariate regression analysis showed in patients who had the
      high-risk genotypes of paraoxonase 1 (PON1) Q192R and endothelial nitric oxide
      synthase (eNOS) E298D that ages at onset of a first MI were 1.8 (p = 0.02) and
      3.5 years (p = 0.02) earlier than in noncarriers of the genotypes, respectively.
      Consistently, high-risk genotypes of the PON1 Q192R and eNOS E298D polymorphisms
      were significantly associated with onset of a first MI at age <50 years (adjusted
      odds ratio 1.70, p = 0.005, adjusted odds ratio 2.15, p = 0.01, respectively). In
      conclusion, our findings suggest that high-risk genotypes of the PON1 Q192R and
      eNOS E298D polymorphisms are independently associated with a significantly
      earlier occurrence of coronary events.

PMID- 17437736
TI  - Association of size of myocardial scar and persistence of ST-segment elevation
      after healing of anterior wall myocardial infarction.
AB  - Half the patients who survive ST-segment elevation anterior myocardial infarction
      continue to have ST elevation (STE) 6 months after the event. The mechanism for
      this and its clinical significance are unclear. There are data to suggest that
      larger infarcts are more likely to have persistent changes in the ST segment.
      This study is designed to test this association further using a novel means of
      assessing the presence and magnitude of myocardial scar using cardiac magnetic
      resonance imaging (MRI). Delayed imaging by MRI after injection of gadolinium is
      commonly used to detect myocardial scar through the appearance of delayed
      contrast hyperenhancement. Consecutive patients referred for myocardial viability
      imaging were reviewed. The volume of scar as a percentage of anterior wall volume
      was calculated, and the 26 patients with scar involving >or=10% of the anterior
      wall were selected for inclusion. All had an electrocardiogram recorded within 15
      days of MRI, and none had an intervening cardiac event. Observers unaware of MRI
      findings independently measured ST-segment changes. Nine patients had STE >1 mm
      and 17 did not. Mean anterior scar volume in the group without STE was 31.9 +/-
      17.1% of the anterior wall volume compared with 50.3 +/- 15.9% in the group with
      STE >1 mm (p = 0.01). The larger the myocardial scar, the more likely STE was to
      be present. Only 1 of 10 patients (10%) with scar in the anterior wall <30% had
      such an elevation compared with 3 of 9 (33%) with scar size of 30% to 49% and 5
      of 7 (78%) with scars >or=50%. In conclusion, persistent anterior STE is
      associated with the size of myocardial scar detected using MRI.

PMID- 17437737
TI  - Effect of left ventricular scar size, location, and transmurality on left
      ventricular remodeling with healed myocardial infarction.
AB  - Studies of patients with acute myocardial infarction (MI) suggest that anterior
      transmural infarcts are associated with greater left ventricular (LV) remodeling
      compared with nontransmural nonanterior infarctions. It is unclear whether this
      relation also exists in long-term survivors of MI. Cardiac magnetic resonance
      imaging was used to explore the relation between myocardial scar size,
      localization, transmurality, and degree of long-term LV remodeling in patients
      with healed MI. Subjects were recruited from a registry of patients with healed
      MI who participated in the OPTIMAAL trial. Cardiac magnetic resonance imaging was
      performed to assess LV mass, volumes, LV ejection fraction, and myocardial
      scarring, adjusting for myocardial ischemia. Fifty-seven patients (mean age 69 +/
      10 years mean ejection fraction 49 +/- 13%) were studied 4.4 +/- 0.4 years after
      MI. Anterior scar was found in 19 patients and nonanterior scar in 33, whereas 5
      patients did not show myocardial scar. Transmural scar was evident in 36
      patients. In the 52 patients with scar, average total scar size was 13 +/- 8% of
      total LV mass. There was a strong linear relation between scar size and LV end
      diastolic volume index (r = 0.81, p <0.0001), end-systolic volume index (r =
      0.86, p <0.0001), and LV ejection fraction (r = -0.74, p <0.0001). In
      multivariate analysis, scar size was the strongest independent predictor of
      ejection fraction and LV volumes independently of scar localization and
      transmurality. In conclusion, in the studied cohort, there was a linear relation
      between scar size and ejection fraction and LV volumes. This relation was
      independent of scar location and transmurality.

PMID- 17437738
TI  - Electrocardiographic recording and timeliness of clinician evaluation in the
      emergency department in patients presenting with chest pain.
AB  - Acute chest pain (CP), a leading symptom of persons presenting to emergency
      departments (EDs), may represent a life-threatening emergency or nonurgent
      condition requiring routine outpatient follow-up. In either case, rapid provision
      of an electrocardiogram and clinician evaluation are essential for determining
      appropriate treatment or discharge from the ED. Data from the National Hospital
      Ambulatory Medical Care Survey were used to estimate the proportion of hospital
      ED visits for a chief symptom of CP in adults aged >or=25 years with
      documentation of both an electrocardiogram and mean and/or median wait time to
      see a clinician in the ED. In 2004, adults aged >or=25 years made nearly 5.3
      million (men 2.5, women 2.8) CP-ED visits. Patients arrived by means of ambulance
      in only 25% of visits. Overall, a quarter of the patients with CP visits waited
      <10 minutes to see a physician in 2003 to 2004. Mean wait time was 36 +/- 1.7
      (SE) minutes, an increase of 5 minutes from that in 1997 to 1998. In 2003 to
      2004, provision of an electrocardiogram was documented for about 80% of all
      patients with CP-related ED visits and 90% of those with visits for
      undifferentiated or cardiac CP. The odds of having an electrocardiogram taken in
      the ED increased (p <or=0.05) for older adults, men, and those triaged as
      emergency cases (vs unknown or no triage) or who waited <10 minutes to see a
      physician (vs >or=10-minute wait time). A large proportion of visits were for
      undifferentiated CP (54%). Cardiac CP accounted for 16% (3% ischemic) and
      noncardiac CP accounted for 30% of visits. Median wait times for a physician were
      12 minutes for those with ischemic CP, 15 minutes for those with other cardiac
      CP, 18 minutes for those with undifferentiated CP, and 25 minutes for those with
      noncardiac CP. From 1993 to 2004, ED visits for CP increased for younger (25 to
      64 years) adults (1993: 15.6 per 1,000 population, 2.5 million visits vs 2004:
      20.9 per 1,000, 4.0 million) and decreased for older adults (>or=65 years) (1993:
      9.7 per 1,000; 1.5 million vs 2004: 7.3 per 1,000; 1.3 million). In conclusion,
      most ED patient visits for undifferentiated and cardiac CP included an
      electrocardiogram and timely clinician evaluation.

PMID- 17437739
TI  - Impact of blood transfusions in patients presenting with anemia and suspected
      acute coronary syndrome.
AB  - Anemia has been shown to predict adverse events in patients presenting with acute
      coronary syndromes and non-ST-elevation myocardial infarctions (MIs). Less is
      known about the value of blood transfusions in this setting. We sought to
      evaluate the impact of red blood cell transfusions on outcomes. Transfusion in
      anemic patients admitted with suspected acute coronary syndrome/non-ST-elevation
      MIs led to a significant increase in 30-day recurrent MI or death (odds ratio
      3.05, 95% confidence interval 1.80 to 5.17, p <0.001). This relation persisted
      after adjusting for significant univariate predictors: hypotension on
      presentation, pulmonary edema, and increased troponin-I levels (odds ratio 2.57,
      95% confidence interval 1.41 to 4.69, p <0.001). In conclusion, the risk versus
      benefit of transfusion in patients presenting with an acute coronary syndrome
      needs careful assessment.

PMID- 17437740
TI  - Analytic approaches to establish the diagnostic accuracy of coronary computed
      tomography angiography as a tool for clinical decision making.
AB  - Although 64-slice multidetector coronary computed tomography angiography (CTA)
      has been reported to have excellent test characteristics for the detection of
      significant coronary artery disease, current analytic approaches may not
      appropriately reflect the process of clinical decision making. Thirty-seven
      patients (29 men; mean age 63 +/- 11 years) who underwent coronary CTA for
      clinical indications followed by invasive coronary angiography within 4 weeks
      were studied. Computed tomography angiograms were analyzed independently for the
      presence of significant coronary artery stenosis (>or=50% luminal narrowing) by 2
      observers blinded to invasive coronary angiographic results. The diagnostic test
      performance of coronary CTA was determined with and without inclusion of
      unassessable segments. Because stenosis could not be excluded in unassessable
      segments, these segments were counted as positive for stenosis. Sensitivity,
      specificity, and positive (PPV) and negative predictive values of CTA for
      detecting significant stenoses on assessable segments were 85% (51 of 60, 95%
      confidence interval [CI] 76% to 94%), 99% (414 of 416, 95% CI 99 to 100), 96%
      (95% CI 51 of 53), and 98% (95% CI 414 of 423), respectively. Overall, 13% of
      coronary segments (70 of 546) were not assessable using CTA (heavy calcium in 48
      segments). By including these segments, PPV decreased from 96% to 60% (74 of
      123), whereas sensitivity improved from 85% to 89% (95% CI 74 of 83). In
      conclusion, the clinical utility of coronary CTA may be limited by a low PPV in
      patients with a high prevalence of coronary artery disease.

PMID- 17437741
TI  - Acute myocardial infarction in patients with versus without aortic valve
      sclerosis and effect of statin therapy (from the Heart and Soul Study).
AB  - Aortic sclerosis is associated with cardiovascular events in patients without
      coronary heart disease (CHD), but it is unclear whether this association exists
      in patients with established CHD or is independent of baseline cardiac disease
      severity. It is also unclear whether statins modify this association. In a
      prospective cohort study of 814 outpatients with established CHD and no evidence
      of aortic stenosis, the association of aortic sclerosis with subsequent
      cardiovascular events was examined using a multivariable Cox proportional hazards
      model. Of 814 participants, 324 (40%) had aortic sclerosis. During 4 years of
      follow-up, 10% with aortic sclerosis experienced a myocardial infarction (MI)
      compared with 5% of those without aortic sclerosis (hazard ratio [HR] 1.8, 95%
      confidence interval [CI] 1.1 to 3.1, p = 0.02). This association was unchanged
      after adjustment for potential confounders and mediators (HR 2.4, 95% CI 1.3 to
      4.8, p = 0.009). However, the association between aortic sclerosis and MI
      appeared to differ by statin use (p = 0.15 for interaction). Aortic sclerosis
      predicted subsequent MI in subjects not administered statins (adjusted HR 4.1,
      95% CI 1.1 to 15.7, p = 0.04), but not in those administered statins (adjusted HR
      1.7, 95% CI 0.8 to 3.9, p = 0.18). In conclusion, aortic sclerosis was present in
      40% of patients with CHD and is independently associated with a 2.4-fold
      increased rate of subsequent MI. Statins may attenuate the increased risk of
      future MI in patients with aortic sclerosis.

PMID- 17437742
TI  - Relation of depression to coronary endothelial function.
AB  - The purpose of this study was to determine the association between depression and
      coronary endothelial function and cardiac risk factors in men and women without
      obstructive coronary artery disease. Patients with no significant coronary artery
      disease who underwent invasive coronary endothelial function assessment with
      acetylcholine were studied. Men and women were divided into 2 groups: those with
      depression and those without. Endothelial function and risk factor profiles were
      compared between the 2 groups. Seven hundred fifty-nine patients were studied,
      603 (79%) without depression and 156 (21%) with depression. Patients with
      depression were more likely to be women (71% vs 60%, p = 0.02), have greater body
      mass indexes (29.9 +/- 6.7 vs 28.2 +/- 5.9 kg/m(2), p = 0.002), and be diabetic
      (12% vs 6%, p = 0.02). Depressed patients also had higher levels of C-reactive
      protein (0.35 vs 0.30 mg/dl, p = 0.02). There was no difference in the change in
      coronary blood flow or diameter in response to acetylcholine between the 2 groups
      in men and women. In conclusion, the results of this study demonstrate that
      depression is not associated with coronary endothelial dysfunction in men and
      women without significant coronary artery disease. It is, however, associated
      with a cluster of cardiac risk factors that are linked to the progression of
      atherosclerotic disease.

PMID- 17437744
TI  - Comparison of prognostic significance of amino-terminal pro-brain natriuretic
      Peptide versus blood urea nitrogen for predicting events in patients hospitalized
      for heart failure.
AB  - N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and blood urea nitrogen
      (BUN) predict outcomes in patients with heart failure (HF). However, it is
      unknown whether NT-pro-BNP is a better prognostic marker than BUN in patients
      hospitalized with HF. Chart reviews were performed on 257 consecutively
      hospitalized patients with HF whose NT-pro-BNP levels were drawn at the time of
      admission. The ability of NT-pro-BNP and BUN to predict the primary end point
      (death or readmission <30 days after discharge) was determined. Seventy-three
      patients (28%) reached the primary end point. Patients who reached the primary
      end point had significantly higher NT-pro-BNP and BUN levels. On multivariate
      regression analysis, the predictive values of BUN and NT-pro-BNP were very
      similar: the hazard ratio for NT-pro-BNP greater than the median was 1.81 (p =
      0.044), and the hazard ratio for BUN greater than the median was 1.83 (p =
      0.039). Analysis of the associations between NT-pro-BNP, BUN, and 30-day death or
      readmission as end points showed that BUN is a better predictor of outcomes
      (hazard ratio 3.15, p = 0.012) than NT-pro-BNP (hazard ratio 1.44, p = 0.399). In
      conclusion, in patients admitted to hospitals with HF, BUN is at least an equal
      prognosticator of HF rehospitalization or death as NT-pro-BNP. BUN outperforms NT
      pro-BNP in predicting mortality in patients with advanced HF. If admitting
      physicians are confident that the diagnosis of HF is correct, then admission NT
      pro-BNP adds little to clinical management.

PMID- 17437743
TI  - Anemia as a risk factor for kidney function decline in individuals with heart
      failure.
AB  - Chronic kidney disease (CKD), anemia, and declining kidney function are
      recognized as risk factors for adverse outcomes in patients with heart failure.
      This analysis was conducted to evaluate whether anemia is a risk factor for
      kidney function decrease in patients with heart failure. Data from the Studies of
      Left Ventricular Dysfunction (SOLVD), a randomized trial of enalapril versus
      placebo in patients with ejection fractions <or=35%, were analyzed. After
      randomization, creatinine measurements were taken at 2 weeks, 6 weeks, 4 months,
      and every 4 months thereafter. The glomerular filtration rate (GFR) was estimated
      using the Modification of Diet in Renal Disease Study (MDRD) equation, and GFR
      slope was calculated. "Rapid decrease" was defined as a decrease in the GFR of
      >or=6 ml/min/1.73 m(2)/year. Anemia was defined as baseline hematocrit <36%.
      Multivariate logistic regression weighted by the number of GFR assessments was
      used to test the relation between anemia and rapid decrease. We also evaluated
      whether CKD (baseline GFR </=60 ml/min/1.73 m(2)) modified the relation between
      anemia and rapid decrease. In the 6,360 subjects, the mean age was 59 years, 31%
      had CKD, and 6% had anemia. Median follow-up was 2 years. In multivariate
      analysis, anemia was associated with a 1.30 increased odds (95% confidence
      interval 1.18 to 1.45) of rapid decrease in GFR. In subjects with CKD, anemia was
      associated with a 1.71 increased odds (95% confidence interval 1.43 to 2.05) of
      rapid decrease, while in subjects without CKD, anemia was associated with a 1.16
      increased odds (95% confidence interval 1.03 to 1.31) of rapid decrease (p for
      interaction <0.001). In conclusion, anemia is associated with a rapid decrease in
      kidney function in patients with heart failure, particularly in those with
      underlying CKD.

PMID- 17437745
TI  - Prognostic importance of pulmonary hypertension in patients with heart failure.
AB  - Pulmonary hypertension is a well-known complication in heart failure, but its
      prognostic importance is less well established. This study assessed the risk
      associated with pulmonary hypertension in patients with heart failure with
      preserved or reduced left ventricular (LV) ejection fractions. Patients with
      known or presumed heart failure (n = 388) underwent the echocardiographic
      assessment of pulmonary systolic pressure and LV ejection fraction. Patients were
      followed for up to 5.5 years. Increased pulmonary pressure was associated with
      increased short- and long-term mortality (p <0.0001 and p = 0.003, respectively).
      This relation was also present when stratifying patients by reduced or preserved
      LV function. A Cox proportional-hazards model apportioned a 9% increase in
      mortality per 5 mm Hg increase in right ventricular systolic pressure (p =
      0.0008), independent of age and known chronic obstructive lung disease, heart
      failure, and impaired renal function. In conclusion, pulmonary hypertension is
      associated with increased short- and long-term mortality in patients with reduced
      LV ejection fractions and also in patients with preserved LV ejection fractions.

PMID- 17437746
TI  - Ventricular arrhythmias during left ventricular assist device support.
AB  - Left ventricular assist devices (LVADs) have been used effectively as a "bridge"
      to cardiac transplantation and as destination therapy in patients with advanced
      heart failure. Ventricular arrhythmias (VAs) have been reported to occur in LVAD
      supported patients, although their incidence, risk factors, and clinical
      significance have not been characterized. In this study, 111 patients who
      received LVAD support as a bridge to cardiac transplantation at the University of
      Pittsburgh Medical Center from January 1987 to June 2001 were evaluated.
      Clinically significant VA was defined as ventricular fibrillation, sustained
      ventricular tachycardia, or nonsustained ventricular tachycardia with symptoms
      requiring antiarrhythmic therapy. Patients were grouped on the basis of the
      presence or absence of VAs. VAs occurred in 24 patients (22%) during device
      support. Ischemic heart disease was the cause of heart failure in 71% of patients
      (17 of 24) in the VA group and 45% of patients (39 of 87) in the group without
      VAs (p <0.05). The mortality rate was significantly higher (p <0.001) during LVAD
      support in the group with VAs (33%) compared with the group without VAs (18%). In
      the group with VAs, the early (<or=1 week) occurrence of VAs was associated with
      a significantly higher (p <0.001) mortality rate (54%) compared with late (>1
      week) occurrence (9%). In conclusion, although clinically significant VAs occur
      in patients with heart failure receiving LVAD support, the overall incidence is
      low. VAs are more frequent in patients with ischemic heart failure, and their
      occurrence is associated with greater mortality. The occurrence of VAs early
      after LVAD implantation, in particular, predicts a higher mortality rate.

PMID- 17437747
TI  - The independent prognostic value of contractile and coronary flow reserve
      determined by dipyridamole stress echocardiography in patients with idiopathic
      dilated cardiomyopathy.
AB  - The aim of this study was to evaluate the prognostic value of Doppler
      echocardiographically derived coronary flow reserve (CFR) in assessing inotropic
      response in patients with idiopathic dilated cardiomyopathy (IDC). One hundred
      thirty-two patients with IDC (90 men; mean age 62 +/- 11 years) were evaluated by
      transthoracic dipyridamole (0.84 mg/kg in 10 minutes) stress echocardiography.
      All patients had ejection fractions <40% (mean 33 +/- 7%) and angiographically
      normal coronary arteries, with New York Heart Association class <or=III. CFR was
      assessed in the left anterior descending coronary artery by pulsed Doppler as the
      ratio of maximal peak vasodilation (dipyridamole) to rest diastolic flow
      velocity. Inotropic reserve was identified as rest-stress variation in wall
      motion score index >0.25. All patients were followed for a median of 24 months.
      Mean CFR was 2.0 +/- 0.5. On individual patient analysis, 48 patients had normal
      CFR (>2), and 84 had abnormal CFR. The mean wall motion score index at rest was
      2.0 +/- 0.33 and decreased to 1.8 +/- 0.4 at peak dipyridamole dose (p <0.000).
      Forty-two patients (32%) had inotropic reserve. During follow-up, 19 patients
      died, and 34 showed worsening of New York Heart Association class. The worst
      outcomes were observed in those patients with abnormal CFR and no inotropic
      reserve with high-dose dipyridamole. In a Cox model, mitral insufficiency (hazard
      ratio [HR] 1.7, 95% confidence interval [CI] 1.1 to 2.8), New York Heart
      Association class (HR 2.0, 95% CI 1.1 to 3.7), abnormal CFR (HR 2.8, 95% CI 1.0
      to 8.5), wall motion score index at rest (HR 3.5, 95% CI 1.3 to 9.8), and the
      absence of inotropic reserve with high-dose dipyridamole (HR 2.3, 95% CI 1.06 to
      5.1) were independent predictors of survival. In conclusion, in patients with
      IDC, CFR is often impaired. Reduced CFR and the absence of an inotropic response
      during vasodilator stress are additive in predicting a worse prognosis.

PMID- 17437748
TI  - Sinus of Valsalva aneurysms--47 years of a single center experience and
      systematic overview of published reports.
AB  - A retrospective study was undertaken to review demographic data, clinical
      presentation, outcomes, and long-term results of surgical repair of sinus of
      Valsalva aneurysms (SVAs). SVAs are a rare anomaly. Surgery is the treatment of
      choice. A retrospective review of an institutional database identified 86
      patients who underwent SVA repair from 1956 to 2003. Follow-up ranged from 3
      months to 40 years. The median age was 45 years (range 5 to 80). Approximately
      44% of the patients had associated aortic regurgitation. Ruptures occurred in 34%
      of patients. The predominant fistula was from the right sinus of Valsalva to the
      right ventricle. Most (65%) were diagnosed by echocardiography, and the remaining
      (35%) were diagnosed on cardiac catheterization. All subjects underwent SVA
      repair. Seventy-two patients (84%) underwent other cardiac procedures at the time
      of aneurysm repair. Six patients (7%) died perioperatively, and the actuarial 10
      year survival rate was 63%. In conclusion, echocardiography is the most
      frequently used diagnostic tool. The most common site of the aneurysm was the
      right coronary sinus. The concomitant surgical repair of associated ventricular
      septal defect, atrial septal defect, and the aortic valve is often required.
      Elective surgical repair can be performed with low risk.

PMID- 17437749
TI  - A non-biased assessment of the usefulness of computed tomographic angiography.

PMID- 17437750
TI  - Regulatory changes for the treatment of patients with heart attacks.
AB  - This editorial discusses the urgent need to reform the regulatory system that
      currently impedes treatment for patients with heart attacks. Existing regulations
      and practices often direct ambulances carrying patients with heart attacks to
      under-equipped facilities, and the absence of necessary advertising guidelines
      results in hospitals without the latest lifesaving technologies intentionally
      misdirecting patients to their facilities through misleading marketing. As a
      result, patients die needlessly. Two congressional responses are recommended in
      this editorial to address this national public health crisis. First, Congress
      should enact legislation similar to that which it created for trauma care,
      resulting in patients in need of critical cardiac care being directed to the most
      appropriate, not merely the closest, facility. Second, Congress should enact
      legislation that would make Medicare participation conditional on hospitals'
      following guidelines on how they may advertise their ability to treat patients
      with heart attacks. In conclusion, Congress should act to save the lives of
      patients with heart attacks currently being lost as a consequence of regulatory
      and market failures.

PMID- 17437751
TI  - The evolving definition of systemic hypertension.

PMID- 17437752
TI  - Fatal and widespread skeletal myopathy confirmed morphologically years after
      initiation of simvastatin therapy.
AB  - A patient is described in whom fatal myopathy occurred, and its cause appears to
      be the consequence of simvastatin therapy.

PMID- 17437753
TI  - Pulmonary hypertension in neurofibromatosis.
AB  - Two cases of severe pulmonary arterial hypertension in patients with
      neurofibromatosis are reported. The published research is reviewed. In
      conclusion, it is suggested that the association between these conditions be
      recognized in the classification of pulmonary hypertension.

PMID- 17437754
TI  - Cross-sectional or longitudinal comparison of mortality among statin and
      nonstatin users.

PMID- 17437755
TI  - Left bundle branch block: a diagnostic challenge in cardiology.

PMID- 17437756
TI  - Left ventricular mass assessment by real-time three-dimensional echocardiography.

PMID- 17437757
TI  - Statin use and age at death: evidence of a flawed analysis.

PMID- 17437761
TI  - Venous thromboembolism and cancer.

PMID- 17437762
TI  - The influence of working memory on reading growth in subgroups of children with
      reading disabilities.
AB  - This 3-year longitudinal study determined whether (a) subgroups of children with
      reading disabilities (RD) (children with RD only, children with both reading and
      arithmetic deficits, and low verbal IQ readers) and skilled readers varied in
      working memory (WM) and short-term memory (STM) growth and (b) whether growth in
      an executive system and/or a phonological storage system mediated growth in
      reading performance. A battery of memory and reading measures was administered to
      84 children (11-17 years of age) across three testing waves spaced 1 year apart.
      The results showed that skilled readers yielded higher WM growth estimates than
      did the RD groups. No significant differentiation among subgroups of children
      with RD on growth measures emerged. Hierarchical linear modeling showed that WM
      (controlled attention), rather than STM (phonological loop), was related to
      growth in reading comprehension and reading fluency. The results support the
      notion that deficient growth in the executive component of WM underlies RD.

PMID- 17437763
TI  - This month in clinical urology.

PMID- 17437766
TI  - Concerns for the future of urological research.

PMID- 17437767
TI  - Molecularly targeted therapies for renal cell cancer: TRAIL research advances.

PMID- 17437768
TI  - Prostate cancer--more information and more questions.

PMID- 17437769
TI  - Excision and primary anastomosis.

PMID- 17437770
TI  - Resident teaching: the orphan of increased clinical productivity.

PMID- 17437771
TI  - Hemospermia.
AB  - PURPOSE: With current diagnostic modalities the proportion of patients diagnosed
      with idiopathic hemospermia has decreased dramatically. The dilemma now is how
      far to investigate these patients since in the majority it is a benign and self
      limiting symptom. MATERIALS AND METHODS: We reviewed the literature on
      hemospermia with particular emphasis on etiology, diagnosis and management. A
      Medline search of the literature for the last 40 years was done and all relevant
      articles were studied in full. RESULTS: Etiological factors are often categorized
      into the various pathophysiological mechanisms. Most cases of hemospermia are the
      result of iatrogenic, inflammatory and infective pathologies. A literature review
      of the etiological studies of hemospermia identified a total of 33 tumors (25
      prostatic) in 931 cases (3.5%). In patients younger than 40 years an infective
      cause in the urogenital tract is the most common etiological factor. Often only
      simple, tailored investigations and appropriate treatment are required. In
      patients older than 40 years with persistent hemospermia or associated symptoms
      such as hematuria it is essential to exclude urogenital malignancy. History,
      examination and simple investigation should also suffice in this group. If the
      diagnosis is still unclear, further investigation in the form of transrectal
      ultrasound, magnetic resonance imaging and cystoscopy is of proven benefit.
      Treatment for hemospermia depends on the underlying pathological condition. In
      most cases bleeding is slight and self-limited, and it may be managed
      expectantly. CONCLUSIONS: The majority of patients can be treated with minimal
      investigations and simple reassurance. In older patients or those with persistent
      hemospermia or associated symptoms modern diagnostic techniques are of proven
      benefit.

PMID- 17437773
TI  - Epithelializing stent for benign prostatic hyperplasia: a systematic review of
      the literature.
AB  - PURPOSE: We systematically reviewed the literature on the effectiveness,
      durability and safety of the UroLume stent for men with benign prostatic
      hyperplasia. MATERIALS AND METHODS: We searched the MEDLINE and EMBASE databases
      for 1989 to 2005. Reference lists of included studies and review articles were
      also searched. We contacted the UroLume manufacturer and key authors for
      additional information. Primary outcomes were treatment failure and urological
      symptom scores. Secondary outcomes were uroflow parameters and minor
      complications. Two reviewers independently assessed the methodological quality of
      the studies and extracted data. RESULTS: A total of 20 case series evaluated the
      UroLume stent in a total of 990 patients with benign prostatic hyperplasia. Of
      the patients 84% who were catheter dependent voided spontaneously after stent
      insertion. Ten studies assessed symptoms before stent insertion and at some point
      within 1 year after stent insertion. All reported decreases in symptom scores,
      including Madsen-Iversen by 7.9 to 14.3 points and International Prostate Symptom
      Score by 10 to 12.4 points. Peak urine flow rates increased by 4.2 to 13.1 ml per
      second. A total of 104 stents (16%) failed in 606 patients who were evaluable at
      1 year and migration was the commonest cause of failure (38 stents or 37%). Most
      patients initially experienced perineal pain or irritative voiding symptoms
      following stent placement. CONCLUSIONS: Of men who were catheter dependent 84%
      voided spontaneously after insertion of a UroLume stent and the improvement in
      symptoms was similar to that seen after transurethral prostate resection.
      However, 1 of 6 men needed the UroLume removed within a year because of
      complications. Inadequate followup prevented conclusions on stent durability
      beyond 1 year. This review supports the recommendation that stents should be
      considered only in patients at high risk.

PMID- 17437774
TI  - Male genital morphology and function: an evolutionary perspective.
AB  - PURPOSE: The genitals are at the forefront of evolution. Advantageous features of
      genital form and function determine which individuals pass their genes to future
      generations. The male genitalia are primarily for sperm deposition but additional
      functions of the penis and its accessory structures are being identified.
      MATERIALS AND METHODS: The literature regarding genital evolution was reviewed.
      RESULTS: This review explains key theories regarding the mechanisms of genital
      evolution. Also discussed are the anatomical and functional adaptations among
      different species that have evolved to optimize fertilization success. Finally,
      these evolutionary influences are discussed in the context of clinically relevant
      human genital morphology and function. CONCLUSIONS: The function of the genitalia
      extends beyond simple sperm transfer. Genital morphology evolves to provide the
      primary and secondary functionality that is critical for successful mating. By
      considering the form and function of human genital morphology in an evolutionary
      context we gain not only an appreciation for its design, but also the potential
      for a deeper understanding of our treatment goals.

PMID- 17437775
TI  - The discovery of the cavernous nerves and development of nerve sparing radical
      retropubic prostatectomy.
AB  - PURPOSE: This review is of the events that led up to the discovery of the
      cavernous nerves and the development of nerve sparing radical retropubic
      prostatectomy. MATERIALS AND METHODS: The correspondence between Pieter J. Donker
      and Patrick C. Walsh, along with the publication folders describing the anatomy
      of the dorsal vein complex, pelvic plexus and cavernous nerves, and pelvic
      fascia, are reviewed. RESULTS: Serendipity had a major role in the fateful
      meeting of Pieter J. Donker and Patrick C. Walsh on February 13, 1981 when they
      dissected out the cavernous nerves in a stillborn male infant. During the next
      year intraoperative observations identified the capsular arteries and veins of
      the prostate as the likely microscopic landmark that could be used in the adult
      male pelvis to identify the microscopic cavernous nerves. Twenty-five years ago,
      on April 26, 1982, the first purposeful nerve sparing radical prostatectomy was
      performed. One year following surgery patient sexual function was normal, and 25
      years later he has retained his quality of life and an undetectable prostate
      specific antigen. CONCLUSIONS: The events that led up to the first nerve sparing
      radical prostatectomy illustrate the influence of serendipity on discovery.

PMID- 17437776
TI  - Bladder and upper tract urothelial cancer.
AB  - PURPOSE: While there are data available indicating the incidence and prevalence
      of bladder and upper tract urothelial cancer, population level data on resource
      use, costs and patterns of care for these cancers are limited. We quantified the
      economic impact of caring for patients with bladder and upper tract urothelial
      cancer, and determined the primary drivers for such costs in the population in
      the United States. MATERIALS AND METHODS: The analytical methods used to generate
      these results have been described previously. RESULTS: An increasing proportion
      of patients with bladder and upper tract urothelial cancer were being treated in
      the outpatient setting. Most care was provided by urologists and visit frequency
      was directly related to disease stage. Only a small proportion of patients
      potentially eligible for chemotherapy, ie those with advanced disease, sought
      specialized care from oncologists. Office based diagnostic tests such as cytology
      were not commonly done, although a substantial number of patients with bladder
      cancer underwent cystoscopy. The use of excretory urography in these patients was
      decreasing, while the use of computerized tomography was increasing. Ileal
      conduits were the most frequently performed type of urinary diversion following
      cystectomy. The cystectomy rate remained unchanged for a decade. Intravesical
      therapy was done infrequently in patients with bladder cancer. Annual costs for
      treating bladder and upper urinary tract cancers were $1 billion and $64 million,
      respectively, in 2000. These costs represented a $164 million increase over 1994
      levels, which outpaced inflation. CONCLUSIONS: The costs of treating bladder
      cancer increased steadily during a 6-year period despite a decrease in inpatient
      care. Coupled with a lack of substantial change in transurethral resection and
      cystectomy rates, this suggests that the primary cost drivers are increased
      outpatient testing, eg computerized tomography and cystoscopy, and an increase in
      the number of diagnosed cases. Greater focus on selective use of testing
      modalities, preventive care such as smoking cessation and earlier identification
      of patients at risk may help curtail further expenditure with regard to managing
      bladder and upper urinary tract cancers.

PMID- 17437777
TI  - Cryptorchidism and hypospadias.
AB  - PURPOSE: We quantified the burden of cryptorchidism and hypospadias in the United
      States by identifying trends in the use of health care resources and estimating
      the economic impact of the disease. MATERIALS AND METHODS: The analytical methods
      used to generate these results were described previously. RESULTS: Cryptorchidism
      is managed almost exclusively in the outpatient setting and insufficient data
      were available on inpatient health care use. Annual inpatient hospitalizations
      for hypospadias decreased by 75% between 1994 and 2000 from 2,669 (2.2/100,000
      children) to 849 (0.6/100,000). Between 1992 and 2000 there were 611,647
      physician office visits (96/100,000 per year) with undescended testis listed as
      the primary diagnosis. The rate of physician office visits for hypospadias by
      commercially insured boys younger than 3 years increased significantly from
      429/100,000 in 1994 to 655/100,000 in 2002. The annualized rate of 18/100,000 in
      1994 to 1996 remained relatively constant during these 3 years. Orchiopexy rates
      were highest in 0 to 2-year-old children, as generally recommended, but a
      substantial minority of these procedures was done in 3 to 10-year-old children.
      Geographic variation was noted with higher ambulatory surgery rates in the
      Northeast and Midwest than in the South and West. Data on commercially insured
      boys younger than 3 years revealed a 1.5-fold overall increase in the rate of
      hypospadias surgery from 321/100,000 in 1994 to 468/100,000 in 2002, reflecting
      the known increase in hypospadias incidence in the United States during the late
      1990 s. CONCLUSIONS: Average cost per hospitalization for hypospadias exceeded
      $5,389 with costs per case higher in children 3 years or older, although there
      were more cases in children younger than 3 years. The cost per case of
      hypospadias was higher in the Northeast and South than in the other regions. Data
      on cryptorchidism are too sparse to provide insights into its downstream economic
      costs.

PMID- 17437778
TI  - Ureteropelvic junction obstruction.
AB  - PURPOSE: We quantified the burden of ureteropelvic junction obstruction in the
      United States by identifying trends in the use of health care resources and
      estimating the economic impact of the disease. MATERIALS AND METHODS: The
      analytical methods used to generate these results were described previously.
      RESULTS: Inpatient hospitalization rates were highest in children younger than 3
      years. Most patients were male and hospitalizations occurred almost exclusively
      at urban centers. Patients with a primary diagnosis of ureteropelvic junction
      obstruction between 1994 and 2000 had an overall decrease in the age adjusted
      rate of inpatient hospitalization from 1.1/100,000 to 0.8/100,000. Physician
      office visits by Medicare beneficiaries with ureteropelvic junction obstruction
      as the primary diagnosis showed stable overall age adjusted rates during the
      reported years. Between 1999 and 2003 mean inpatient length of stay and cost per
      child hospitalized with the primary diagnosis of ureteropelvic junction
      obstruction was 2.9 days and $7,728, respectively. Average length of stay
      decreased more for children than for adults but total inpatient spending remained
      stable at about $12 million. CONCLUSIONS: The majority of ureteropelvic junction
      obstructions are diagnosed in the perinatal period. Surgical intervention for
      pediatric patients has decreased with time, while there has been an increasing
      trend toward the conservative management of this condition.

PMID- 17437779
TI  - Vesicoureteral reflux and ureteroceles.
AB  - PURPOSE: We quantified the burden of vesicoureteral reflux and ureteroceles in
      the United States by identifying trends in the use of health care resources and
      estimating the economic impact of the diseases. MATERIALS AND METHODS: The
      analytical methods used to generate these results were described previously.
      RESULTS: Annual inpatient hospitalizations for vesicoureteral reflux increased
      slightly between 1994 and 2000 from 6.4/100,000 to 7.0/100,000 children, although
      this trend did not attain statistical significance. Inpatient hospitalization for
      ureteroceles remained relatively stable between 1994 and 2000 at an average of
      approximately 2,818 cases annually (1.0/100,000 to 1.1/100,000 children). The
      rates of visits to physician offices doubled during the 1990 s for commercially
      insured children (12/100,000 in 1994 and 26/100,000 in 2002) and children covered
      by Medicaid (43/100,000 in 1996 and 85/100,000 in 2000). Overall the rate of
      ambulatory surgery visits by commercially insured children increased from
      3.4/100,000 in 1998 to 4.8/100,000 in 2002. Similar estimates were not available
      for children covered by Medicaid. Emergency room use by children with a primary
      diagnosis of vesicoureteral reflux was rare, reflecting the trend toward delivery
      of care at physician offices, ambulatory surgery centers and inpatient hospitals.
      No reliable data could be obtained on outpatient visits or ambulatory surgery for
      ureteroceles. In 2000 total expenditures for inpatient pediatric vesicoureteral
      reflux were $47 million, an increase of more than $10 million since 1997. Based
      on data from 2000 the yearly national inpatient expenditures from ureterocele
      treatment were an estimated $4 million. CONCLUSIONS: The economic impact of
      inpatient treatment for pediatric vesicoureteral reflux is considerable. If other
      service types such as pharmaceuticals, and outpatient and ambulatory services
      were considered, the observed impact of this condition would certainly be
      greater. Importantly the costs of prophylactic medical therapy and emerging
      therapies such as Deflux are not accounted for in this estimate. Furthermore,
      indirect economic costs, such as work loss to parents of children with pediatric
      vesicoureteral reflux, were not considered, causing an even greater
      underestimation of the true costs associated with the condition. Although the
      National Association of Children's Hospitals and Related Institutions, and the
      Health Care Cost and Utilization Project Kids' Inpatient Database include data on
      ureteroceles, the data were limited and, thus, they could not be used to
      determine reliable cost trends. Available data indicate that the mean cost per
      ureterocele case was almost $8,000 with little variation observed across ages,
      regions or sexes.

PMID- 17437780
TI  - Male urethral stricture disease.
AB  - PURPOSE: The incidence of urethral stricture disease in the United States is
      unknown. We estimated the impact of urethral stricture disease by determining its
      prevalence, costs and other measures of burden, including side effects and the
      need for surgical intervention. MATERIALS AND METHODS: Analyses of services for
      urethral stricture disease were performed in 10 public and private data sets by
      epidemiological, biostatistical and clinical experts. RESULTS: Male urethral
      stricture disease occurred at a rate as high as 0.6% in some susceptible
      populations and resulted in more than 5,000 inpatient visits yearly. Yearly
      office visits for urethral stricture numbered almost 1.5 million between 1992 and
      2000. The total cost of urethral stricture diseases in 2000 was almost $200
      million, not including medication costs. A diagnosis of urethral stricture
      increased health care expenditures by more than $6,000 per individual yearly in
      insured populations after controlling for comorbidities. Urethral stricture
      disease appeared to be more common in the elderly population and in black
      patients, as measured by health care use. In most data sets services provided for
      urethral stricture disease decreased with time. Patients with urethral stricture
      disease appeared to have a high rate of urinary tract infection (41%) and
      incontinence (11%). CONCLUSIONS: Despite decreasing rates of urethral strictures
      with time the burden of urethral stricture disease is still significant,
      resulting in hundreds of millions of dollars spent and hundreds of thousands of
      caregiver visits yearly.

PMID- 17437781
TI  - Erectile dysfunction.
AB  - PURPOSE: Male sexual health has taken on increased importance as the United
      States population ages, develops coexisting medical conditions and undergoes
      interventions that can affect sexual function. We characterized the burden and
      severity of disease, treatment patterns and economic consequences of erectile
      dysfunction. MATERIALS AND METHODS: The analytical methods used to generate these
      results were described previously. RESULTS: Erectile dysfunction was self
      reported by almost 1 of 5 men and it increased with age. Erectile dysfunction may
      have been more commonly reported in Hispanic men and in those with a history of
      diabetes, obesity, smoking and hypertension. In most databases black American men
      had rates of use for office visits and inpatient hospital care that were twice
      those of other racial groups, although these rates were not controlled for
      comorbid conditions or other regional and socioeconomic factors. The use of
      diagnostic tests markedly decreased, while pharmacological therapy, especially
      with oral phosphodiesterase-5 inhibitors, markedly increased. Penile implant
      surgery continued to be performed with most patients electing inflatable devices.
      Extrapolating from the population based estimates of erectile dysfunction
      prevalence and current use trends showed that the cost of treatment nationwide
      could reach $15 billion if all men sought treatment. CONCLUSIONS: The burden of
      disease due to erectile dysfunction in the United States will increase with the
      aging of the male population, increasing prevalence of comorbid conditions,
      expanded treatment seeking behavior and costs of pharmaceutical therapy. Accurate
      estimates of economic cost will require better understanding of pathogenesis,
      treatment seeking behavior, patient preference for therapies, success of
      treatments and relative satisfaction with oral pharmacotherapy and penile
      implants.

PMID- 17437782
TI  - Does stage T3a renal cell carcinoma embrace a homogeneous group of patients?
AB  - PURPOSE: Renal cell carcinoma invading the perinephric fat is classified as a
      stage T3a tumor in the 2002 TNM version. Based on long-term followup we examined
      the prognostic significance of this definition. MATERIALS AND METHODS: We
      evaluated the outcome in 237 consecutive patients with localized renal cell
      carcinoma operated on between January 1985 and December 1997. Median followup was
      8 years. Disease-free survival was analyzed using univariate and multivariate
      analyses. Based on this we proposed and tested a new TNM system against the 2002
      TNM version. RESULTS: Tumor recurrence was diagnosed in 48 patients (20.2%) at a
      median of 21.5 months. Diameter based analysis of stage T3a revealed that this
      was an inhomogeneous group that included patients with small tumors and an
      excellent prognosis along with patients with large tumors and a poor prognosis.
      Based on this information we initiated a modified TNM staging system that ignores
      perinephric fat invasion. In the proposed staging system stage T1a includes
      tumors 4 cm or less and stage T1b includes tumors more than 4 but 7 cm or less.
      Stage T2 is divided into T2a-tumors greater than 7 but 10 cm or less and T2b
      tumors greater than 10 cm. Stage T3a is reserved for renal vein tumor invasion.
      The proposed TNM performed better than the 2002 version using the Nagelkerke R(2)
      test (0.439 vs 0.359), and the Hosmer and Lemeshow test (0.335 vs 0.191).
      CONCLUSIONS: The current definition of stage T3a renal cell carcinoma embraces an
      inhomogeneous group of patients with marked differences in prognosis. We believe
      that tumor invasion into the perinephric fat does not necessarily predict
      aggressive biological behavior.

PMID- 17437783
TI  - Impact of clinicopathological parameters in patients treated for renal cell
      carcinoma.
AB  - PURPOSE: We determined the impact of clinical and pathological factors in the
      outcome of patients with renal cell carcinoma treated surgically. MATERIALS AND
      METHODS: We retrospectively reviewed the records of 230 consecutive patients
      after radical or partial nephrectomy. We analyzed clinical (incidental or
      symptomatic disease) and pathological (tumor size, histological type, Fuhrman
      nuclear grade, microvascular invasion and lymph node involvement) parameters.
      Disease-free and cancer specific survival curves were individualized for each
      parameter and on multivariate analysis. RESULTS: Median postoperative followup
      was 34.3 months, median time to recurrence was 22 months and mean overall
      survival was 130 months. A total of 40 patients (17.3%) presented with local
      and/or metastatic recurrence and 32 (13.9%) died of the disease. Five-year
      disease-free and cancer specific survival rates on univariate analysis were 56.7%
      and 64% for symptomatic tumors, 76.6% and 68% for clear cell carcinoma, 26.9% and
      39% for sarcomatoid tumors, 34.7% and 47.5% for high grade tumors, 26.7% and
      39.7% for microvascular invasion, 37.5% and 49.1% for tumors larger than 7 cm,
      and 11% and 32% for lymph node involvement, respectively. On univariate analysis
      patients with lymph node involvement and microvascular invasion had a poor
      prognosis. Multivariate analysis showed that the single independent prognostic
      factor was microvascular invasion. CONCLUSIONS: This study points out different
      clinical and pathological prognostic factors of survival in patients treated for
      renal cell carcinoma. Microvascular invasion was the only independent prognostic
      factor on multivariate analysis.

PMID- 17437785
TI  - Tumor size predicts synchronous metastatic renal cell carcinoma: implications for
      surveillance of small renal masses.
AB  - PURPOSE: Active surveillance of small incidental renal masses is associated with
      slow radiographic growth and a low risk of metastatic progression. Radiographic
      tumor size, in the absence of histological data, is the only prognostic indicator
      available when considering active surveillance. To better define the relationship
      between tumor size and the metastatic potential of small renal masses, we
      investigated whether radiographic tumor size predicts for the presence of
      synchronous metastases in renal cell carcinoma. MATERIALS AND METHODS: We
      reviewed our institutional tumor registry to identify sporadic pathologically
      verified renal cell carcinoma treated during an 8-year period. We analyzed data
      regarding primary tumor size and the presence of biopsy proven synchronous
      metastatic disease at presentation. All N+M0 and nonpathologically confirmed M+
      disease was excluded from analysis. RESULTS: We compared 110 cases of renal cell
      carcinoma with biopsy proven synchronous metastatic disease at presentation to
      250 controls with clinically localized renal cell carcinoma. Tumors associated
      with synchronous metastasis were significantly larger than localized lesions
      (median 8.0 cm [range 2.2 to 20.0] vs 4.5 cm [range 0.3 to 17.5], p <0.0001). The
      probability of synchronous metastasis increased with increasing primary tumor
      size (p <0.0001). There were no patients with tumors 2 cm or smaller who
      presented with biopsy confirmed metastatic disease and less than 5% (5 of 110) of
      all synchronous metastasis occurred in tumors 3.0 cm or smaller. Logistic
      regression models determined that the odds of synchronous metastasis increased by
      22% for each 1 cm increase in tumor size. CONCLUSIONS: Radiographic tumor size is
      a significant clinical predictor of the presence of biopsy proven synchronous
      metastatic renal cell carcinoma. In our series the odds of presenting with
      synchronous, biopsy proven metastatic disease increased by 22% with each 1 cm
      increase in tumor size. A 100% odds increase, or doubling of the risk of
      metastasis, occurs with a 3.5 cm increase in primary tumor size. These data have
      important implications for extent of disease evaluations in patients with large
      tumors and for the active surveillance of small enhancing renal masses.

PMID- 17437788
TI  - Prospective multicenter phase II study of gemcitabine plus platinum salt for
      metastatic collecting duct carcinoma: results of a GETUG (Groupe d'Etudes des
      Tumeurs Uro-Genitales) study.
AB  - PURPOSE: Collecting duct carcinoma of the kidney is a rare and aggressive
      neoplasm of the distal collecting tubules for which there is no established
      treatment. Since the histology of collecting duct carcinoma is similar to that of
      urothelial carcinoma, the standard chemotherapy regimen defined by a gemcitabine
      and platinum salts combination was prospectively investigated in patients with
      metastatic collecting duct carcinoma. MATERIALS AND METHODS: A total of 23
      patients with metastatic collecting duct carcinoma with no prior systemic
      chemotherapy were treated with 1,250 mg/m(2) gemcitabine on days 1 and 8 plus 70
      mg/m(2) cisplatin or carboplatin (AUC 5) in patients with renal insufficiency on
      day 1. The drugs were repeated every 21 days for 6 cycles according to toxicity
      and efficacy. The objective response rate was the primary end point. RESULTS:
      There were 1 complete and 5 partial responses for an objective response rate of
      26% (95% CI 8 to 44). Median progression-free and overall survival was 7.1 (95%
      CI 3 to 11.3) and 10.5 months (95% CI 3.8 to 17.1), respectively. Toxicity was
      mainly hematological with grade 3-4 neutropenia and thrombocytopenia in 52% and
      43% of patients, respectively. The severity of granulocytopenia and the number of
      metastatic sites were associated with overall survival on univariate and
      multivariate analyses. CONCLUSIONS: To our knowledge this is the first
      prospective, multicenter, phase II study showing that the platinum salts
      combination is an active and safe regimen as first line treatment in patients
      with metastatic collecting duct carcinoma. This platinum based chemotherapy
      should be considered the standard regimen in these patients.

PMID- 17437789
TI  - Renal cell carcinoma with tumor thrombus extension into the vena cava:
      prospective long-term followup.
AB  - PURPOSE: We prospectively evaluated long-term survival in patients with renal
      cell carcinoma extending to the inferior vena cava. MATERIALS AND METHODS: From
      1993 and thereafter we followed 86 men and 48 women with a median age of 64 years
      (range 28 to 86) with renal cell carcinoma and tumor thrombus involvement of the
      inferior vena cava. Cancer specific survival was analyzed based on clinical
      therapy, tumor extent, thrombus level and grading. RESULTS: Median followup was
      16.4 months (range 0 to 178.9). At the time of this report 97 cancer specific
      deaths had occurred. Of the 134 patients 111 underwent radical nephrectomy,
      cavotomy and thrombus extraction, of whom 30 had distant metastases at surgery,
      and 23 were treated with embolization and immunotherapy. These nonsurgical
      patients who refused surgery had a high tumor load or a low Karnofsky performance
      status that may have affected survival. They died at a median of 6.9 months
      (range 0.1 to 23.6). Patients treated surgically, including those with
      metastases, had a significantly higher median survival of 19.8 months (range 0 to
      178.9). Surgical patients with localized tumor (N0M0) had significantly higher
      median survival than those with metastatic (NxM1) disease (51.7 months, range 0
      to 178.9 vs 6.9, range 0.6 to 149.7). Surgical patients with metastatic disease
      who underwent interferon and interleukin based immunotherapy had significantly
      higher median survival than those who did not (13.5 months, range 2.5 to 149.7 vs
      5.1, range 0.6 to 24.0). On multivariate analysis localized tumor stage (N0M0) vs
      advanced tumor stage (N+M0 and NxM1), Fuhrman grade groups 1 and 2 vs 3 and 4,
      and tumor thrombus levels I and II vs III and IV were independent prognostic
      factors. CONCLUSIONS: Currently radical surgery represents the only chance of
      long-term survival for patients with renal cell carcinoma and tumor thrombus
      extension in the inferior vena cava. Median cancer specific survival is
      significantly higher with localized tumor. However, even with metastatic disease
      radical surgery can prolong survival, especially when immunotherapy is added.
      Fuhrman grade and tumor thrombus level are also prognostic factors.

PMID- 17437791
TI  - Analysis of complications following partial and total nephrectomy for renal
      cancer in a population based sample.
AB  - PURPOSE: We determined the frequency and predictors of complications of partial
      and total nephrectomy in a population based sample. MATERIALS AND METHODS: There
      were 3,019 partial and 18,575 total nephrectomies identified from the Nationwide
      Inpatient Sample data set of the Healthcare Cost and Utilization Project (2000 to
      2003). The prevalence of International Classification of Diseases, 9th Revision
      coded complications following nephrectomy was determined. Hospital and patient
      related factors associated with the occurrence of a complication were determined
      by logistic regression analysis. We evaluated the impact of complications on in
      hospital mortality, length of stay and hospital charges. RESULTS: Respiratory,
      digestive and bleeding complications were the most common, with similar patterns
      for partial nephrectomy and total nephrectomy. Significant predictors of
      complications after total nephrectomy included age, male sex, comorbidity
      severity index and hospital location (rural vs urban), while comorbidity was the
      only significant predictor for partial nephrectomy complications. Any
      complication had a significant impact on in-hospital mortality, total charges and
      length of stay. Digestive and urinary complications, hemorrhage, and
      postoperative infections had a significant impact on in-hospital mortality after
      partial nephrectomy, while these same complications, in addition to respiratory
      and cardiac complications, had a significant impact on total charges and length
      of stay. All except digestive complications had a significant impact on
      mortality, hospital charges and length of stay for patients undergoing total
      nephrectomy. CONCLUSIONS: In a population based cohort partial nephrectomy and
      total nephrectomy are associated with low morbidity and mortality profiles, and
      all complications affect mortality, length of hospital stay and charges.

PMID- 17437794
TI  - Behavior of urothelial carcinoma with respect to anatomical location.
AB  - PURPOSE: Urothelial carcinoma is a disease of the entire urothelium. Recent
      molecular insights suggest that the biology of some upper urinary tract and
      bladder urothelial carcinoma differ. These differences may affect tumor
      phenotype. Observational studies conflict as to the significance of anatomical
      location on the behavior of urothelial carcinoma. We compared the biological
      outcome in a large series of urothelial carcinoma with respect to anatomical
      location. MATERIALS AND METHODS: We analyzed urothelial carcinoma in 425 patients
      treated at 4 centers according to stage and anatomical location, including the
      bladder in 275, the ureter in 67 and the renal pelvis in 79. Relapse surveillance
      was performed for a median of 46 months (range 2 to 216). A separate invasive
      bladder urothelial carcinoma population was also included to pathologically
      balance upper and lower tract urothelial carcinoma cases to allow behavioral
      comparisons. RESULTS: As a whole, upper urinary tract urothelial carcinoma is
      more invasive and worse differentiated than bladder cancer (chi-square test
      p<0.0001 and 0.015, respectively). In pathologically matched cohorts recurrence
      to less aggressive disease, progression to more advanced disease and death
      occurred in 37%, 40% and 44% of patients with bladder urothelial carcinoma, and
      in 41%, 44% and 43% of those with upper urinary tract urothelial carcinoma,
      respectively. Multivariate analysis revealed that tumor stage and grade (Cox
      p=0.0001 and 0.012, respectively) but not location were associated with behavior.
      CONCLUSIONS: Urothelial carcinoma behaves identically in the upper and lower
      urinary tracts when stage and grade are considered. The majority of tumors
      relapse within 5 years of excision. The current move to minimally
      invasive/nephron sparing techniques for urothelial carcinoma of the upper urinary
      tract appears safe. Care could be analogous to that for bladder urothelial
      carcinoma.

PMID- 17437796
TI  - Endoscopic management of upper tract urothelial carcinoma in patients with a
      history of bladder urothelial carcinoma.
AB  - PURPOSE: Endoscopic management of renal pelvis and ureteral urothelial carcinoma
      is gaining acceptance as a conservative treatment modality. Patients with a
      history of bladder urothelial carcinoma are at high risk for upper tract
      recurrence. We evaluate the role of endoscopic management of upper tract
      urothelial carcinoma in patients with a history of primary bladder urothelial
      carcinoma. MATERIALS AND METHODS: We retrospectively reviewed 90 patients with a
      history of primary bladder urothelial carcinoma who underwent endoscopic
      treatment of localized upper tract urothelial carcinoma between 1983 and 2004.
      RESULTS: Median patient age at diagnosis was 73 years (range 50 to 90). A total
      of 13 (14.4%) patients previously underwent cystectomy. With a median followup of
      4.3 years (range 0.1 to 17), 105 upper tract urothelial carcinoma recurrences
      developed in 55 patients at a mean of 0.6 years (range 22 days to 5.9 years). Of
      these recurrences 76 were amenable to endoscopic management while 29 required
      nephroureterectomy. In 38 patients there were 91 bladder recurrences. At last
      followup 48 patients died, 17 of urothelial carcinoma at a median of 3.4 years
      (range 1 to 10). Cancer specific survival at 5 years for this cohort was 71.2%.
      Risk of death from urothelial carcinoma was significantly associated with stage
      (RR 3.23) and grade (RR 4.05) of upper tract urothelial carcinoma, imperative
      indication (RR 4.30), and treatment of bladder urothelial carcinoma with
      cystectomy (RR 3.34). CONCLUSIONS: Endoscopic management of upper tract
      urothelial carcinoma in patients with primary bladder urothelial carcinoma
      demonstrates a significant local recurrence rate. Furthermore, 5-year cancer
      specific survival is low. These patients represent a high risk cohort requiring
      strict ureteroscopic followup after endoscopic management is instituted.

PMID- 17437798
TI  - Patterns of recurrence and outcomes following induction bacillus Calmette-Guerin
      for high risk Ta, T1 bladder cancer.
AB  - PURPOSE: The standard approach to treatment for patients with high risk Ta, Tis,
      or T1 bladder cancer that persists or recurs after bacillus Calmette-Guerin is
      radical cystectomy in medically fit patients. Maintenance bacillus Calmette
      Guerin has been shown in both SWOG (Southwest Oncology Group) and EORTC (European
      Organization for Research and Treatment of Cancer) studies to reduce the
      probability of disease worsening events. As new drugs come on line and experience
      with maintenance and combination immunotherapy increases, there may be a tendency
      to delay definitive local therapy and thereby expose patients to a higher risk of
      progression to invasive and potentially metastatic disease. We explored a large
      prospective data set from the SWOG 8507 randomized trial of maintenance bacillus
      Calmette-Guerin to better understand this risk and specifically to assess the
      impact of timing of recurrence on survival. MATERIALS AND METHODS: The database
      includes 501 evaluable patients who were treated with induction bacillus Calmette
      Guerin and then were randomized to maintenance bacillus Calmette-Guerin or
      observation. Recurrence patterns were defined as early (less than 12 months
      following randomization) or late (12 or more months after randomization).
      Patients were identified who underwent cystectomy at any time after induction
      bacillus Calmette-Guerin. All patients were followed for life for determination
      of vital status. Outcome measure of overall survival was assessed using Kaplan
      Meier analysis and adjustment for covariates was done with proportional hazards
      models. Survival was defined from date of randomization to death from any cause.
      RESULTS: A total of 501 patients were randomized after induction bacillus
      Calmette-Guerin, of whom 251 had recurrence and 229 died. Of the patients who
      died 59% had recurrence following randomization. Early recurrence was not
      associated with a higher risk of death compared to late recurrence (p=0.68).
      There was no evidence that bacillus Calmette-Guerin affected the relationship of
      timing of relapse and survival. There was no difference in progression to T2 or
      greater between early and late recurrence (38 of 117, 32% vs 34 of 134, 25%;
      p=0.21). Cystectomy was performed infrequently as 56 of 251 patients who had
      recurrence underwent the operation. Patients who had early recurrence had a
      slightly higher cystectomy rate than those with late recurrence (32 of 117, 27%
      vs 24 of 134, 18%; p=0.07). Among 394 patients with no evidence of disease at
      randomization those who underwent cystectomy for T2 or greater disease had a
      higher risk of death compared to patients who underwent cystectomy for Tis or T1
      disease (HR 1.76; 95% CI 0.77, 4.00; p=0.18). CONCLUSIONS: There was no
      association of the timing of recurrence after induction bacillus Calmette-Guerin
      on long-term survival probability. When patients had early recurrence there was a
      slightly higher probability of cystectomy but not progression to muscle invasive
      cancer. When cystectomy was performed the 5-year postoperative survival
      probability was lower than that reported in contemporary series.

PMID- 17437801
TI  - Early prostate cancer antigen expression in predicting presence of prostate
      cancer in men with histologically negative biopsies.
AB  - PURPOSE: Early prostate cancer antigen is a nuclear matrix protein that was
      recently shown to be expressed in prostate adenocarcinoma and adjacent benign
      tissue. Previous studies have demonstrated early prostate cancer antigen
      expression in benign prostate tissue up to 5 years before a diagnosis of prostate
      carcinoma, suggesting that early prostate cancer antigen could be used as a
      potential predictive marker. MATERIALS AND METHODS: We evaluated early prostate
      cancer antigen expression by immunohistochemistry using a polyclonal antibody
      (Onconome Inc., Seattle, Washington) on benign biopsies from 98 patients.
      Biopsies were obtained from 4 groups that included 39 patients with first time
      negative biopsy (group 1), 24 patients with persistently negative biopsies (group
      2), 8 patients with initially negative biopsies who were subsequently diagnosed
      with prostate carcinoma (group 3) and negative biopsies obtained from 27 cases
      where other concurrent biopsies contained prostate carcinoma (group 4). Early
      prostate cancer antigen staining was assessed by 2 of the authors who were blind
      to the group of the examined sections. Staining intensity (range 0 to 3) and
      extent (range 1 to 3) scores were assigned. The presence of intensity 3 staining
      in any of the blocks of a biopsy specimen was considered as positive for early
      prostate cancer antigen for the primary outcome in the statistical analysis. In
      addition, as secondary outcomes we evaluated the data using the proportion of
      blocks with intensity 3 early prostate cancer antigen staining, the mean of the
      product of staining intensity and staining extent of all blocks within a biopsy,
      and the mean of the product of intensity 3 staining and extent. RESULTS: Primary
      outcome analysis revealed the proportion of early prostate cancer antigen
      positivity to be highest in group 3 (6 of 8, 75%) and lowest in group 2 (7 of 24,
      29%, p=0.04 for differences among groups). A relatively higher than expected
      proportion of early prostate cancer antigen positivity was present in group 1 (23
      of 39, 59%). Early prostate cancer antigen was negative in 41% of group 4 who
      were known to harbor prostate carcinoma. The proportion of early prostate cancer
      antigen positivity was statistically significantly lower in group 2 than in each
      of the other groups when compared pairwise. A lower proportion of early prostate
      cancer antigen positivity was encountered in older archival tissue blocks
      (p<0.0001) pointing to a potential confounding factor. Corrected for block age,
      group 3 was the only group to remain statistically significantly different in
      early prostate cancer antigen positivity compared to the reference group 2.
      Similar findings were obtained when adjustments for patient age were made and
      when analysis was based on secondary outcome measurements. CONCLUSIONS: Our study
      showed a higher proportion of early prostate cancer antigen expression in initial
      negative prostate biopsy of patients who were diagnosed with prostate carcinoma
      on subsequent followup biopsies. We found a relatively high proportion of early
      prostate cancer antigen positivity (59%) in the group with first time negative
      biopsies and a potential 41% rate of false-negative early prostate cancer antigen
      staining in benign biopsies from cases with documented prostate carcinoma on
      concurrent cores. The lower early prostate cancer antigen positivity in cases
      with older blocks raises the question of a confounding effect of block age.
      Additional studies on the antigenic properties of early prostate cancer antigen
      in archival material are required to further delineate the usefulness of early
      prostate cancer antigen immunostaining on biopsy material.

PMID- 17437802
TI  - Influence of prostate volume and percent free prostate specific antigen on
      prostate cancer detection in men with a total prostate specific antigen of 2.6 to
      10.0 ng/ml.
AB  - PURPOSE: Percent free prostate specific antigen and prostate specific antigen
      density have been independently shown to increase the specificity of prostate
      cancer screening in men with prostate specific antigen levels between 4.1 and
      10.0 ng/ml. Recent data suggest the total prostate specific antigen cutoff for
      performing a biopsy should be 2.6 ng/ml. We assessed the influence of percent
      free prostate specific antigen and prostate volume on cancer detection in men
      with a prostate specific antigen between 2.6 and 10.0 ng/ml. MATERIALS AND
      METHODS: From 1991 to 2005 all transrectal ultrasound guided prostate biopsies
      (5,587) for abnormal digital rectal examination and/or increased age specific
      prostate specific antigen were evaluated. A total of 1,072 patients with a
      prostate specific antigen between 2.6 and 10.0 ng/ml and any percent free
      prostate specific antigen were included in study. The cancer detection rate was
      calculated for each percent free prostate specific antigen/volume stratum.
      RESULTS: Prostate cancer was detected in 296 patients (27.6%). The mean age and
      prostate specific antigen of the patients with benign pathology and prostate
      cancer were similar. Mean percent free prostate specific antigen was 17.5% and
      14.1% (p>0.05), and the mean volume was 62.0 and 46.0 cc (p=0.001), respectively.
      The strongest risk factors for a positive biopsy were percent free prostate
      specific antigen (odds ratio 0.004, p<0.001), volume (OR 0.977, p<0.001) and
      digital rectal examination (OR 1.765, p=0.007), but not total prostate specific
      antigen (p=0.303). When stratified by volume and percent free prostate specific
      antigen, distinct risk groups were identified. The probability of detecting
      cancer inversely correlated with prostate volume and percent free prostate
      specific antigen. CONCLUSIONS: In men with prostate specific antigen levels
      between 2.6 and 10.0 ng/ml, the probability of detecting cancer was inversely
      proportional to prostate volume and percent free prostate specific antigen. This
      table may assist in predicting patient risk for harboring prostate cancer.

PMID- 17437803
TI  - Risk of prostate cancer for young men with a prostate specific antigen less than
      their age specific median.
AB  - PURPOSE: We previously reported that the median prostate specific antigen for men
      40 to 49 years old is 0.7 ng/ml and that a baseline prostate specific antigen
      between 0.7 and 2.5 ng/ml is associated with a 14.6-fold increased risk of
      prostate cancer. Although this suggests the need for close followup of men in
      their 40s with a prostate specific antigen level greater than 0.7 ng/ml, the
      appropriate screening strategy for men with a level less than the age specific
      median is unclear. MATERIALS AND METHODS: From a large prostate cancer screening
      study 581 participants 40 to 49 years old with a baseline prostate specific
      antigen level less than 0.7 ng/ml were identified. All men were classified as
      high risk due to a positive family history and/or black heritage. Changes in
      prostate specific antigen over time, the cancer detection rate and pathological
      tumor features were examined as a function of the baseline prostate specific
      antigen. RESULTS: At a median followup of 13 months 2 patients with an initial
      prostate specific antigen level less than 0.7 ng/ml reached the threshold for
      biopsy, and a single patient was diagnosed with prostate cancer. A significantly
      greater proportion of men with a baseline prostate specific antigen level greater
      than the age specific median had a prostate specific antigen velocity greater
      than 0.75 ng/ml per year (9% vs 3%, p=0.009) and were diagnosed with prostate
      cancer before age 50 (4.6% vs 0.16%, p<0.0001). CONCLUSIONS: Men 40 to 49 years
      old with a prostate specific antigen less than the age specific median have a low
      risk of prostate cancer in the short term. Performing a baseline prostate
      specific antigen measurement in the fifth decade led to few additional biopsies,
      and was extremely useful for risk stratification since men with levels greater or
      less than the age specific median had strikingly different risk profiles.

PMID- 17437804
TI  - Finasteride improves the sensitivity of digital rectal examination for prostate
      cancer detection.
AB  - PURPOSE: Men undergoing screening for prostate cancer are recommended to undergo
      digital rectal examination and prostate specific antigen measurement. We
      previously presented data from the Prostate Cancer Prevention Trial indicating
      that finasteride improves the performance characteristics of prostate specific
      antigen for cancer detection. In the current study we report the impact of
      finasteride on digital rectal examination sensitivity and specificity. MATERIALS
      AND METHODS: We examined the sensitivity and specificity of digital rectal
      examination in Prostate Cancer Prevention Trial subjects receiving finasteride or
      placebo who underwent prostate biopsy, had prostate specific antigen measurement
      and digital rectal examination within 1 year before biopsy and were on treatment
      at biopsy. RESULTS: Of 9,423 men in the finasteride group 4,579 and 5,112 of
      9,459 in the placebo group met study evaluation requirements. Of 4,579 men in the
      finasteride group 695, including 264 with Gleason 7 or greater and 81 with
      Gleason 8 or greater, and 1,111 of 5,112 in the placebo group, including 240 with
      Gleason 7 or greater and 55 with Gleason 8 or greater, were diagnosed with
      prostate cancer. In men in the placebo and finasteride groups digital rectal
      examination sensitivity was greater for detecting higher grade tumors. The
      sensitivity of digital rectal examination was significantly greater for cancer
      detection in men receiving finasteride than placebo (21.3% vs 16.7%, p=0.015).
      Digital rectal examination sensitivity was also greater for detecting high grade
      (Gleason 7 or greater and 8 or greater) cancers in men receiving finasteride but
      this did not attain statistical significance. Digital rectal examination
      specificity was similar in men receiving finasteride or placebo. CONCLUSIONS:
      Finasteride significantly improves prostate cancer detection with digital rectal
      examination.

PMID- 17437806
TI  - Discovery and validation of 3 novel DNA methylation markers of prostate cancer
      prognosis.
AB  - PURPOSE: About 15% of men experience prostate specific antigen recurrence after
      radical prostatectomy. A DNA methylation based molecular test could provide
      important information to predict which patients are most likely to experience
      recurrence. MATERIALS AND METHODS: We performed a genome-wide scan to find
      aberrantly methylated loci in prostate cancer from patients with early
      recurrence, high Gleason score or advanced stage. We discovered 441 candidate
      methylation markers and further analyzed 62 candidates in a methylation
      microarray study of 304 frozen prostatectomy samples. RESULTS: Methylation of 25
      markers was significantly changed in high Gleason score (8-10) vs low Gleason
      score (2-6) cancers. Methylation levels of the 3 marker candidates GPR7, ABHD9
      and an expressed sequence tag on chromosome 3 (Chr3-EST) were significantly
      increased in patients who did vs did not experience early PSA recurrence
      (Bonferroni correction p<0.05). Furthermore, these markers were also informative
      when the sample set was restricted to 68 mid range Gleason score (6 or 7) samples
      only. We developed real-time polymerase chain reaction assays for ABHD9 and Chr3
      EST, and measured methylation in paraffin embedded, formalin fixed prostatectomy
      samples from an independent set of 223 patients. Methylation of the 2 markers was
      significantly higher in patients with early PSA recurrence compared to that in
      patients who did not experience PSA recurrence. CONCLUSIONS: We report that
      methylation of the 3 novel markers GPR7, ABHD9 and Chr3-EST is significantly
      associated with prostate cancer prognosis. Incorporation of these methylation
      markers into clinical practice will result in more accurate prediction of which
      patients are likely to experience PSA recurrence.

PMID- 17437808
TI  - Patterns of local failure following prostate brachytherapy.
AB  - PURPOSE: We describe biopsy results in patients with prostate cancer treated with
      brachytherapy. MATERIALS AND METHODS: A total of 1,562 men with localized
      prostate cancer were treated with permanent prostate brachytherapy, of whom 508
      agreed to ultrasound guided biopsies 2 years after the completion of all therapy.
      Median followup was 6.7 years (range 2 to 14.6) and median prostate specific
      antigen was 7.4 ng/ml (range 0.3 to 300). Disease was categorized as Gleason
      score less than 7 in 74.8% of patients, stage T2a or less in 64.2%, low risk in
      43.1%, intermediate risk in 24.2% and high risk in 32.7%. Of the 508 men 315
      (62%) received (125)I, 110 (21.7%) received (103)Pd and 83 (16.3%) received
      (103)Pd and external beam radiotherapy. A total of 237 men (46.7%) received a
      short course of hormonal therapy (3 to 9 months). Subsequent biopsies were
      performed after 2 years if initial biopsy was positive or prostate specific
      antigen increased. Post-implantation dosimetry results were grouped into low,
      normal and high dose. Associations were tested by chi-square analysis. Survival
      functions were calculated with Kaplan-Meier analysis and Cox regression. RESULTS:
      A total of 643 biopsies were performed in 508 men between 2 and 11 years after
      implantation. Of the 508 men 39 (7.7%) had a final positive biopsy. Positive
      biopsy was associated with high prostate specific antigen (p=0.035), stage
      (p=0.003), risk (p=0.024), no hormonal therapy (p=0.002) and low dose (p<0.0001).
      On multivariate analysis only dose and hormonal therapy were significant
      (p<0.0001 and p=0.004, respectively). Of the patients 80% were free of PSA
      failure at 10 years if final biopsy was negative compared to 27.3% with a
      positive biopsy (p<0.0001). Death from prostate cancer was associated with a
      positive biopsy (OR 18.5, 95% CI 2.3-143, p<0.0001). Of the 52 men with a
      positive biopsy at year 2, 23 (44.2%) had negative results on subsequent biopsy,
      while 10 of the 456 (2.2%) with negative 2-year biopsies showed positive results.
      Positive biopsy occurred in the prostate only in 31 of 39 men (79.5%), in the
      prostate and seminal vesicles in 3 (7.7%), and in the seminal vesicles only in 5
      (12.8%). CONCLUSIONS: Patients undergoing prostate brachytherapy must receive an
      adequate radiation dose to eradicate local disease. Hormonal therapy may benefit
      local control in patients with intermediate to high risk disease. Extraprostatic
      biopsies should be performed in patients with local failure who are considering
      salvage therapy to rule out seminal vesicle involvement.

PMID- 17437812
TI  - Laparoscopic extraperitoneal radical prostatectomy in complex surgical cases.
AB  - PURPOSE: Patients with a high body mass index, previous pelvic surgery or large
      prostate size are not considered ideal candidates for radical prostatectomy. We
      assessed the impact of body mass index, previous pelvic surgery and prostate
      weight on perioperative and pathological outcomes in patients treated exclusively
      with laparoscopic extraperitoneal radical prostatectomy. MATERIALS AND METHODS:
      From January 2004 to May 2005, 300 patients underwent laparoscopic
      extraperitoneal radical prostatectomy. Patients were divided into groups,
      including body mass index groups 1 (25 kg/m(2) or less), 2 (25.1 to 30), 3 (30.1
      to 36) and 4 (greater than 36); prostate weight groups 1 (20 gm or less), 2 (20.1
      to 40), 3 (40.1 to 60) and 4 (more than 60); and prior surgery groups 1 (no
      previous pelvic or prostatic surgery) and 2 (previous pelvic or prostatic
      surgery). RESULTS: Logistic regression demonstrated that body mass index, large
      prostate size and previous pelvic surgery did not affect margin status. The
      Kruskal-Wallis test was performed to analyze if body mass index, large prostate
      size and previous pelvic surgery had an effect on perioperative variables. Only
      prostate weight correlated with a delay in Foley catheter removal (3 days,
      p=0.0005). The Wilcoxon rank sum test showed that patients with a higher body
      mass index had a slightly prolonged hospital stay (16 hours, p=0.02). Patients
      with a prostate of more than 40 gm had slightly increased blood loss (56 cc,
      p=0.03), which did not affect the transfusion rate. CONCLUSIONS: Laparoscopic
      extraperitoneal radical prostatectomy can be performed in complex surgical cases
      without increased perioperative morbidity. Obese patients and those with a large
      prostate who prefer surgery as a treatment option for localized prostate cancer
      may benefit from the advantages that laparoscopic extraperitoneal radical
      prostatectomy offers.

PMID- 17437815
TI  - Do tumor volume, tumor volume ratio, type of nerve sparing and surgical
      experience affect prostate specific antigen recurrence after laparoscopic radical
      prostatectomy? A matched pair analysis.
AB  - PURPOSE: We assessed the impact of tumor volume, tumor volume ratio (tumor volume
      to-prostate volume), surgical experience and type of nerve sparing procedure on
      biochemical recurrence after laparoscopic radical prostatectomy. MATERIALS AND
      METHODS: Of 1,600 laparoscopic radical prostatectomies performed between March
      1999 and May 2006 we evaluated 555 patients who had at least 24 months of
      followup and received neither neoadjuvant nor adjuvant therapy. Of 555 patients
      81 had biochemical recurrence and were match paired in 3 groups with those
      without recurrence. Matching decisions were based on factors such as age,
      preoperative prostate specific antigen, pathological stage, Gleason score,
      surgical margin status with localization, tumor volume, type of nerve sparing
      procedure, surgeon and date of operation that are related to surgical experience.
      We evaluated the impact of tumor volume and tumor volume ratio, type of nerve
      sparing procedure and surgeon on biochemical recurrence, and excluded the factor
      being investigated in each matched pair. RESULTS: Tumor volumes were 3.58 vs 3.3
      cc and tumor volume ratios were 0.081 vs 0.071 in the biochemical recurrence and
      no biochemical recurrence groups, respectively (p=0.026 and p=0.040). At the
      second match pair the numbers of nonnerve sparing, unilateral and bilateral nerve
      sparing procedures were 65, 12 and 4 vs 62, 13 and 6, respectively, without
      statistical significance. At the last match pair the volume of cases for the
      first generation and the other generations were 56 and 25 vs 59 and 22,
      respectively, also without statistical significance. CONCLUSIONS: Although
      surgical experience based on an adequate training program and type of nerve
      sparing procedure do not have a significant impact on biochemical recurrence,
      tumor volume and tumor volume ratio do.

PMID- 17437819
TI  - Adjuvant weekly docetaxel for patients with high risk prostate cancer after
      radical prostatectomy: a multi-institutional pilot study.
AB  - PURPOSE: Patients with adverse pathological features are at high risk for
      recurrence following radical prostatectomy. To improve outcomes in this
      population we performed a phase II study of adjuvant docetaxel in these high risk
      patients. MATERIALS AND METHODS: Patients with nonmetastatic radical
      prostatectomy at greater than 50% risk for recurrence by 3 years were eligible.
      Pathological findings were centrally reviewed and risk assessment was based on a
      validated multivariate Cox proportional hazards model. Treatment consisted of 6
      cycles of 35 mg/m(2) docetaxel weekly given 4 to 12 weeks following surgery.
      Progression was defined as a prostate specific antigen of 0.4 ng/ml or greater,
      radiological/pathological evidence of recurrent disease or death from any cause.
      To screen for the potential benefit of adjuvant weekly docetaxel we used nomogram
      predicted progression-free survival as a historical control. RESULTS: A total of
      77 patients were registered between April 2002 and January 2004. Two patients had
      grade IV hyperglycemia and 20 had grade III toxicity. At a median followup of
      29.2 months (range 1.6 to 39.2) 46 of 76 evaluable cases (60.5%) progressed.
      Observed median progression-free survival was 15.7 months (95% CI 12.8-25.1).
      Predicted median progression-free survival in a matched population was 10 months.
      Seven patients died, including 4 of prostate cancer, 1 with intra-abdominal
      bleeding during treatment and 2 of pneumonia and sudden cardiac death,
      respectively, following treatment. CONCLUSIONS: Adjuvant docetaxel for prostate
      cancer is feasible with significant reversible but acceptable toxicity. The
      actual median progression-free survival of 15.7 months was longer than the
      nomogram predicted rate for this patient population. Adjuvant docetaxel treatment
      should be further evaluated in phase III trials in patients with high risk
      prostate cancer.

PMID- 17437820
TI  - Effect of medical management on recurrent stone formation following percutaneous
      nephrolithotomy.
AB  - PURPOSE: Percutaneous nephrolithotomy is a commonly used procedure for treatment
      of large or complex renal calculi. In some instances postoperative residual stone
      fragments are an unavoidable result. Yet to our knowledge no study has examined
      the impact of medical management on stone formation in patients with or without
      residual fragments following percutaneous nephrolithotomy. Thus, we have
      conducted the first investigation of aggressive medical management following
      percutaneous nephrolithotomy and its impact on stone formation rates in patients
      with and without residual fragments. MATERIALS AND METHODS: A total of 70
      patients who underwent percutaneous nephrolithotomy and received counseling
      regarding selective medical management following a comprehensive metabolic
      evaluation, were identified. Patients were placed into 4 groups following
      percutaneous nephrolithotomy, that is stone-free or residual fragments, who
      underwent or did not undergo medical therapy. New stone formation was assessed by
      spontaneous stone passage in the absence of residual stone fragments, stone
      passage without change in the number of residual fragments, surgical removal of
      newly formed stones, or appearance of new stones or increase in size of stone or
      fragments on abdominal radiographs. Stone remission rates were also calculated.
      RESULTS: Selective medical therapy significantly decreased stone formation rates
      in the stone-free (0.67 stones per patient per year vs 0.02) and residual
      fragment groups (0.67 stones per patient per year vs 0.02) as determined by the
      Wilcoxon signed rank test (p<0.0001). Moreover, remission was observed in a
      higher proportion of patients in the medically treated stone-free and residual
      fragment groups (87% and 77%) when compared to the same groups without medical
      therapy (29% and 21%, chi-square test p<0.0001). CONCLUSIONS: Our findings
      suggest that comprehensive metabolic evaluation and aggressive medical management
      can control active stone formation and growth in patients with or without
      residual stone fragments after percutaneous nephrolithotomy. Given the inherent
      morbidity and increased costs attendant with repeat procedures, medical
      management should be instituted in patients following percutaneous
      nephrolithotomy without regard to stone-free status.

PMID- 17437822
TI  - Bowel dysfunction after transposition of intestinal segments into the urinary
      tract: 8-year prospective cohort study.
AB  - PURPOSE: Bowel function may be disturbed after intestinal segments are transposed
      into the urinary tract to reconstruct or replace the bladder. In 1997 our group
      was the first to report major bowel dysfunction in a cohort of such patients. Up
      to 42% of those who were asymptomatic preoperatively described new bowel symptoms
      postoperatively including explosive diarrhea, nocturnal diarrhea, fecal urgency,
      fecal incontinence and flatus leakage. We now describe bowel symptoms in this
      same cohort 8 years later (2005). MATERIALS AND METHODS: A total of 116 patients
      were evaluable. Of the remaining 37 from the original study 30 had died, 5 no
      longer wished to be involved and 2 could not be located. Patients were asked to
      complete postal questionnaires identical to those used in the first followup,
      assessing the severity of bowel symptoms and quality of life using 2 validated
      instruments. Responses were compared with those from the original study. The
      Nottingham Health Profile quality of life scores were also compared to age and
      sex matched norms. RESULTS: There were 96 patients (83%) who completed 8-year
      followup questionnaires, including 43 after ileal conduit diversion (group 1), 17
      after clam enterocystoplasty for overactive bladder (group 2), 18 after bladder
      reconstruction for neurogenic bladder dysfunction (group 3) and 18 with bladder
      replacement for nonneurogenic causes (group 4). High prevalence rates of bowel
      symptoms persisted with no statistically significant differences between the 2
      times. Of those with symptoms in 2005, approximately 50% had reported similar
      symptoms in 1997. Patients treated with clam enterocystoplasty (group 2) still
      reported the highest prevalence (59%) of troublesome diarrhea with 1 in 2 on
      regular antidiarrheal medication. They also had high rates of fecal incontinence
      (47%), fecal urgency (41%) and nocturnal bowel movement (18%), and a large number
      reported a moderate or severe adverse effect on work (36%), social life (50%) and
      sexual activity (43%). High rates were also reported by patients with neurogenic
      bladder dysfunction, including 50% with troublesome diarrhea. This symptom was
      reported by 19% after ileal conduit and by 17% after bladder replacement for
      nonneurogenic causes. The impact of bowel symptoms on everyday activities and
      quality of life persisted, remaining most severe after clam enterocystoplasty,
      with 24% regretting undergoing the procedure because of subsequent bowel
      symptoms. CONCLUSIONS: After more than 8 years, operations involving
      transposition of intestinal segments continue to be associated with high rates of
      bowel symptoms which impact everyday activities. These are particularly
      troublesome following enterocystoplasty for overactive bladder and bladder
      reconstruction for neurogenic bladder dysfunction. These risks should influence
      patient selection and potential patients should be warned before undergoing
      surgery.

PMID- 17437823
TI  - The technique of vessel sparing excision and primary anastomosis for proximal
      bulbous urethral reconstruction.
AB  - PURPOSE: We present a technique not previously described for proximal bulbous or
      bulbomembranous urethral reconstruction of excision and primary anastomosis. The
      technique has the potential advantages of preserving the proximal urethral blood
      supply. MATERIALS AND METHODS: From June 2003 to October 2006, 10 patients
      underwent vessel sparing urethral reconstruction including 3 after radical
      prostatectomy, 6 following straddle trauma and 1 potentially with a congenital
      stricture. A plane was developed between the urethra and the proximal blood
      supply at the bulbospongiosum, allowing for division of the urethra without
      dividing the spongy tissue of the corpus spongiosum or the arteries to the bulb.
      Only 7 patients are presented for data analysis because the other 3 have not had
      sufficient followup to date. RESULTS: Patient age range was 15 to 72 years (mean
      47). The patient with a congenital stricture was 2 years old. Stricture length
      ranged from 0.5 to 2.5 cm (mean 1.5). The patients who had undergone radical
      prostatectomy were either incontinent or were believed to be possibly rendered
      incontinent after the urethral reconstruction. At a mean followup of 12.5 months
      (range 6 to 38) all 7 patients had patent urethras, 2 were incontinent and 1
      underwent implantation with an AMS 800 sphincter using a transcorporal approach.
      As of this writing all 10 patients are apparently stricture-free. CONCLUSIONS:
      Preservation of blood supply is always a noble achievement in surgery. However,
      it technically often requires significant effort. In patients after radical
      prostatectomy with proximal anterior urethral or bulbomembranous strictures,
      preserving the blood supply possibly decreases cuff erosion when undergoing later
      implantation Many patients (approximately 12% lifetime risk of prostate cancer)
      will require radical prostatectomy and may later require a sphincter. Further
      studies are warranted to evaluate the benefit of applying this technique in all
      suitable patients.

PMID- 17437824
TI  - Long-term followup for excision and primary anastomosis for anterior urethral
      strictures.
AB  - PURPOSE: We report our experience and long-term followup of patients undergoing
      excision and primary anastomotic reconstruction for anterior urethral strictures.
      MATERIALS AND METHODS: From July 1986 to May 2006 the charts of 260 patients who
      underwent excision with primary anastomosis at our center for bulbar urethral
      stricture were reviewed. Patient age ranged from 14 to 78 years (mean 38.4),
      stricture length ranged 0.5 to 4.5 cm (mean 1.9). Patients who had surgery within
      the last 5 years were contacted by telephone if their 6-month postoperative
      cystoscopic evaluation was patent and they had not visited the clinic afterward.
      RESULTS: After a mean followup of 50.2 months 257 patients (98.8%) were symptom
      free and required no further procedures. Recurrent stricture occurred early in 2
      patients and late in 1 patient. Two patients opted for intermittent dilations,
      and a single direct visual internal urethrotomy was performed in 1 patient 4
      years postoperatively. One of the patients who elected dilation subsequently
      elected urethral reconstruction, which was done successfully. Complications
      encountered were position related neuropraxia in 9 (3.4%), early urinary tract
      infection in 13 (5%), chest related in 5 (1.9%), scrotalgia in 4 (1.5%) and wound
      related in 4 (1.5%). All resolved within the early postoperative period. Erectile
      dysfunction was encountered in 6 (2.3%) patients, of whom 4 had a history of
      significant straddle trauma, 4 responded well to oral pharmacotherapy and 1
      elected to not have the erectile dysfunction treated. CONCLUSIONS: Excision with
      primary anastomosis for anterior urethral stricture has a high success rate of
      98.8% with durable long-term results in most patients. Complications are few, of
      short duration and self-limited. Where applicable, we believe that the procedure
      clearly is the choice for short anterior urethral strictures.

PMID- 17437826
TI  - The relationships among measures of incontinence severity in women undergoing
      surgery for stress urinary incontinence.
AB  - PURPOSE: We assessed the relationships among severity measures of urinary
      incontinence in women with stress predominant symptoms enrolled in a randomized
      clinical trial comparing 2 surgical techniques (Burch colposuspension vs
      pubovaginal sling) for stress urinary incontinence. MATERIALS AND METHODS: A
      total of 655 women underwent a standardized preoperative assessment that included
      the Medical, Epidemiological and Social Aspects of Aging questionnaire,
      Urogenital Distress Inventory, Incontinence Impact Questionnaire, 3-day voiding
      diary, 24-hour pad test, a supine empty bladder stress test and Valsalva leak
      point pressure measurements. Correlations were estimated using Spearman
      correlation coefficients and 95% confidence intervals. T tests at alpha=0.05 were
      conducted to compare the distributions of the continuous severity measure between
      patients with positive and negative supine empty bladder stress test. RESULTS:
      Baseline mean scores on Medical, Epidemiological and Social Aspects of Aging,
      Urogenital Distress Inventory and Incontinence Impact Questionnaire were 25.8,
      151 and 171, respectively. Mean incontinence episode frequency and pad weight
      were 3.2 per day and 43.5 gm, respectively. Supine empty bladder stress test was
      positive in 218 patients, and 428 patients had valid Valsalva leak point pressure
      measurements with a mean Valsalva leak point pressure of 80 cm H(2)O. Weak to
      moderate correlations were observed between Medical, Epidemiological and Social
      Aspects of Aging, incontinence episode frequency, pad weight, Incontinence Impact
      Questionnaire and Urogenital Distress Inventory. On the other hand, Valsalva leak
      point pressure correlated poorly with all variables measured. The sensitivity and
      specificity of the supine empty bladder stress test to predict intrinsic
      sphincter dysfunction were 49% and 60%, respectively. CONCLUSIONS: Urinary
      incontinence severity measures correlate moderately with each other at best.
      While Medical, Epidemiological and Social Aspects of Aging demonstrated stronger
      correlations with the other measures of severity and quality of life, Valsalva
      leak point pressure did not. Supine empty bladder stress test did not demonstrate
      a clinically significant association among severity measures.

PMID- 17437827
TI  - Symptoms suggestive of chronic pelvic pain syndrome in an urban population:
      prevalence and associations with lower urinary tract symptoms and erectile
      function.
AB  - PURPOSE: We determined the prevalence of symptoms suggestive of chronic pelvic
      pain syndrome in an urban population and assessed associations with lower urinary
      tract symptoms and erectile dysfunction. MATERIALS AND METHODS: Men participating
      in a voluntary health examination free of charge that was organized by the
      Department of Preventive Health of the City of Vienna were analyzed. All
      participants completed 3 validated questionnaires on chronic pelvic pain syndrome
      (National Institutes of Health-Chronic Prostatitis Symptom Index), lower urinary
      tract symptoms (International Prostate Symptom Score) and erectile dysfunction
      (International Index of Erectile Function-5). RESULTS: A total of 1,765 men with
      a mean +/- SD age of 46.3 +/- 0.3 years (range 20 to 79) entered this study. The
      mean National Institutes of Health-Chronic Prostatitis Symptom Index score
      increased from 4.0 +/- 0.3 in the youngest age group of 20 to 29-year-old men to
      6.3 +/- 0.6 in those 70 to 79 years old. The overall prevalence of symptoms
      suggestive of chronic pelvic pain syndrome, defined by a pain score of 4 or
      greater and perineal/ejaculatory pain, was 2.7% and it revealed no age
      dependence, such as the pain score. In contrast, urinary symptom and quality of
      life scores increased with age. International Index of Erectile Function-5 score
      was 20.6 +/- 0.3 for men without chronic pelvic pain symptoms vs 18.3 +/- 0.7 for
      men with mild symptoms and 16.5 +/- 1.1 for men with moderate/severe symptoms. A
      National Institutes of Health-Chronic Prostatitis Symptom Index score in the
      upper quartile was associated with 8.3-fold increased odds of erectile
      dysfunction. CONCLUSIONS: The prevalence of symptoms suggestive of chronic pelvic
      pain syndrome in this large cohort of men participating in a health screening
      project was 2.7% and it revealed no age dependence. Our study suggests that
      chronic pelvic pain syndrome has a negative impact on erectile function.

PMID- 17437828
TI  - Computerized tomographic angiography for renal donor evaluation leads to a higher
      exclusion rate.
AB  - PURPOSE: We compared the exclusion rate for potential living renal donors
      evaluated with computerized tomography angiography and radionuclide renal
      scintigraphy (renal scan) vs excretory urogram, renal scan and renal
      arteriography. MATERIALS AND METHODS: From March 2004 through February 2006, 603
      consecutive patients were evaluated as potential living renal donors. From March
      2004 through February 2005, 270 consecutive patients underwent evaluation with
      excretory urogram, renal scan and renal angiography (group 1). Of these patients
      16 underwent computerized tomography to evaluate abnormalities detected on
      excretory urogram. From March 2005 through February 2006, 333 consecutive
      patients underwent evaluation with computerized tomography angiography and renal
      scan (group 2). The number of patients excluded for medical reasons and/or
      radiographic abnormalities was determined for the 2 groups. RESULTS: More than
      twice as many patients evaluated with computerized tomography were excluded. In
      group 1, 7% of patients (20 of 270) were excluded from donation due to
      radiographic findings vs 16% (53 of 333) in group 2 (p=0.0016). Of the patients
      26% and 23% were excluded from renal donation for medical reasons in groups 1 and
      2, respectively (p=0.5059). CONCLUSIONS: Multidetector row computerized
      tomography angiography increases the detection of incidental radiographic
      abnormalities as well as the renal donor exclusion rate. The increased
      sensitivity of computerized tomography angiography has created a dilemma for
      those determining patient eligibility for kidney donation because the clinical
      significance of many of these findings is unclear. Additional studies should
      address the significance of these incidental findings so that patients are not
      needlessly excluded from kidney donation.

PMID- 17437831
TI  - Sexual function is a determinant of poor quality of life for women with treatment
      refractory interstitial cystitis.
AB  - PURPOSE: Interstitial cystitis significantly negatively impacts quality of life.
      The demographic and clinical factors associated with decreased quality of life in
      these patients have not been well studied. MATERIALS AND METHODS: Women with
      moderate/severe interstitial cystitis enrolled in a clinical trial of
      intravesical bacillus Calmette-Guerin were studied. Demographic data and
      responses to questionnaires were evaluated at baseline, including the O'Leary
      Sant Interstitial Cystitis Symptom Index and Problem Index, University of
      Wisconsin Interstitial Cystitis Inventory, Medical Outcomes Study sexual
      functioning scale, and the physical composite and mental composite scales of the
      Medical Outcomes Study Short Form Health Status Survey. Three composite indexes
      were constructed (from the O'Leary-Sant Interstitial Cystitis Symptom Index,
      O'Leary-Sant Interstitial Cystitis Problem Index, pain/urgency Likert scales and
      24-hour voiding diary) to document the severity, frequency and bother of pain,
      urinary urgency and frequency (frequency composite index). Linear and
      multivariate regression models were used to examine predictors of the physical
      composite and mental composite scales of the Medical Outcomes Study Short Form
      Health Status Survey. Medical Outcomes Study sexual functioning scale data were
      available for 163 of the 217 women in the trial. RESULTS: Physical composite
      scale (median 36) and mental composite scale (median 42) were lower than the
      standard population value of 50. Multivariate models showed that employment, pain
      composite index and Medical Outcomes Study sexual functioning scale (all p<0.001)
      predicted physical composite scale, while only Medical Outcomes Study sexual
      functioning scale (p<0.001) remained a strong predictor of mental composite
      scale. CONCLUSIONS: Sexual functioning, employment and pain issues predict mental
      and physical quality of life. In particular, this study identifies sexual
      functioning as a primary predictor of mental quality of life in women with long
      standing interstitial cystitis. It is suggested that sexual functioning may be a
      salient therapeutic target in the multifaceted treatment of patients with
      interstitial cystitis.

PMID- 17437832
TI  - Office based flexible cystoscopy may be less painful for men allowed to view the
      procedure.
AB  - PURPOSE: An experienced urology nurse observed that patients seemed to tolerate
      the procedure better when allowed to see the monitor in real time during office
      based cystoscopy. We assessed the impact of this on visual analog scale pain
      scores. MATERIALS AND METHODS: A total of 100 consecutive male patients underwent
      flexible cystoscopy, as performed by a single surgeon during the study period.
      Patients were randomized into 2 groups. Patients in group 1 were allowed to
      visualize the video screen with the surgeon, while patients in group 2 had the
      screen positioned so that only the surgeon could visualize the procedure. Water
      soluble lubricant was used on all endoscopes and all men received 10 cc 2%
      viscous lidocaine intraurethral before cystoscopy. No sedatives or analgesics
      were administered. All patients provided consent before the procedure and they
      were asked to record their pain experience on a 100 mm visual analog pain scale
      as soon as the surgeon left the room. RESULTS: Men who were allowed to visualize
      the cystoscopy had lower visual analog scale pain scores than those who were
      unable to visualize the screen (14 vs 23, Wilcoxon rank sum test p=0.02).
      CONCLUSIONS: To our knowledge no study has shown the impact of distraction of
      cystoscopic findings on procedure pain levels. Men viewing cystoscopy on the
      video monitor experienced an approximately 40% decrease in the pain level
      compared to those who did not view the procedure on the monitor. We encourage
      office urologists to incorporate this useful point of technique during flexible
      cystoscopy.

PMID- 17437833
TI  - Racial disparities in the surgical management of stress incontinence among female
      Medicare beneficiaries.
AB  - PURPOSE: The relationship between urinary incontinence and race/ethnicity is
      poorly understood. We analyzed Medicare claims data to identify racial
      differences in the diagnosis, treatment and outcomes of women with stress urinary
      incontinence. MATERIALS AND METHODS: We analyzed the 1999 to 2001 Medicare Public
      Use Files provided by the Centers for Medicare and Medicaid Services on a 5%
      national random sample of beneficiaries. Women 65 years or older with a diagnosis
      of stress urinary incontinence were identified on the basis of International
      Classification of Diseases, 9th revision codes. Those who underwent an autologous
      or synthetic sling procedure during the index period were identified on the basis
      of Physicians Current Procedural Terminology Coding System, 4th edition codes.
      Racial differences in diagnosis, treatment and outcomes were compared. RESULTS:
      Of all female Medicare beneficiaries older than 65 years overall only 1.1% had a
      claim that listed a diagnosis of stress urinary incontinence. White women were
      more likely than nonwhite women to have a claim listing a diagnosis of stress
      urinary incontinence. Approximately 27,120 slings were performed on the Medicare
      population during the study period. Among women with a diagnosis of stress
      urinary incontinence white and Hispanic women were disproportionately more likely
      to undergo a sling than were black or Asian women (p<0.01). After controlling for
      age and comorbidities, nonwhite women undergoing sling surgery were twice as
      likely to develop nonurological complications, pelvic organ prolapse and urinary
      obstruction within 1 year postoperatively. CONCLUSIONS: We identified racial
      differences in the frequency of diagnosis of stress urinary incontinence,
      frequency of sling procedures and rate of postoperative complications after sling
      surgery. Further research is necessary to determine whether such differences are
      due to racial differences in incontinence incidence and severity or disparities
      in care for minorities.

PMID- 17437834
TI  - Prostate cancer knowledge among low income minority men.
AB  - PURPOSE: We identified sociodemographic characteristics that predict poor disease
      understanding in low income, uninsured men with prostate cancer. MATERIALS AND
      METHODS: A total of 399 low income, uninsured men with prostate cancer
      participating in the Men's Health Survey done by researchers at University of
      California-Los Angeles Jonsson Comprehensive Cancer Center completed
      questionnaires assessing their knowledge of prostate cancer. Logistic regression
      was used to identify sociodemographic factors, eg age, education level, language
      preference, ethnicity and relationship status, associated with poor prostate
      cancer knowledge. RESULTS: Most subjects were Latino (54% or 213 of 399), spoke
      English (53% or 213 of 399) and had a high school education or less (86% or 344
      of 399). In the multivariate model increasing age (p<0.014) and less than a high
      school education (p<0.012) were associated with lower knowledge of disease, while
      Latino ethnicity and relationship status were not. CONCLUSIONS: Among low income
      men with prostate cancer increasing age and less formal education were associated
      with lower knowledge of disease. Further study is needed to determine the roles
      of language preference and ethnicity in the understanding of the disease in
      patients with prostate cancer.

PMID- 17437836
TI  - Health related quality of life in Japanese men with localized prostate cancer
      treated with current multiple modalities assessed by a newly developed Japanese
      version of the Expanded Prostate Cancer Index Composite.
AB  - PURPOSE: Health related quality of life in Japanese men with localized prostate
      cancer treated with current multidisciplinary treatment modalities was assessed
      using a newly developed Japanese version of the Extended Prostate Cancer Index
      Composite. We evaluated psychometric properties of the Japanese version of the
      Extended Prostate Cancer Index Composite. MATERIALS AND METHODS: A cross
      sectional analysis of health related quality of life was done in 460 patients
      treated with radical prostatectomy, external beam radiation therapy, permanent
      (125)I seed implantation androgen deprivation therapy or watchful waiting.
      Patients were enrolled in January to July 2005. Serum testosterone was measured
      in all participants. RESULTS: Missing values ranged from 0.4% to 16.3% with 10%
      or greater observed for 15 of 50 items (30%). A missing value of 10% or greater
      correlated with higher age and lower educational background (p<0.05). Internal
      consistency reliability was 0.7 or higher for almost all subscales except the
      bowel function and hormonal function subscales. Test-retest reliability and
      factor validity were successfully verified. Known groups validity revealed
      significant improvement in urinary domain scores with time in patients treated
      with radical prostatectomy plus permanent (125)I seed implantation. Bowel domain
      scores were worse in patients treated with external beam radiation therapy
      compared to the other modalities. Decreased hormonal domain scores correlated
      with low serum testosterone (p<0.001). Salvage androgen deprivation therapy after
      radical prostatectomy negatively influenced sexual function but not sexual
      bother. CONCLUSIONS: Reliability and validity of the Japanese version of the
      Extended Prostate Cancer Index Composite were verified, although revision is
      needed for it to be more comprehensible for elderly patients and those with low
      education. It can be used for cross-cultural assessment of health related quality
      of life in patients with localized prostate cancer treated with current
      multidisciplinary treatment modalities.

PMID- 17437837
TI  - Laparoscopic treatment of urachal remnants in children.
AB  - PURPOSE: Urachal remnants are generally treated with the open method. We
      evaluated the role of laparoscopy for this anomaly in a consecutive series of 27
      children treated during a 12-year period. MATERIALS AND METHODS: A total of 27
      children with a median age of 4.7 years presented with urachal remnants between
      1993 and 2006. Two different laparoscopic approaches were used. In the first 9
      children a 5 mm laparoscope was inserted at the umbilicus, with working trocars
      in the left and right upper abdominal wall. In the remaining patients the
      laparoscope was placed at the left lower abdominal wall, with working ports
      placed at the left lower and upper abdomen. The working ports were 2 mm trocars.
      The urachal remnants were ligated and excised by electrocautery, and the bladder
      sided stump was ligated with 2 sutures. No drains were used. The specimen were
      exteriorized via the umbilicus. RESULTS: Median operative time was 35 minutes.
      There were no intraoperative or postoperative complications, and no recurrences.
      Cosmetic results were excellent. CONCLUSIONS: The laparoscopic approach for
      urachal remnants is safe, allows for better visualization of the anatomy and
      yields a cosmetic result that is superior to the open approach.

PMID- 17437838
TI  - Percutaneous nephrolithotomy in children: lessons learned in 5 years at a single
      institution.
AB  - PURPOSE: We retrospectively compared morbidity and success rates in children who
      underwent percutaneous nephrolithotomy with 3 different sizes of instruments.
      MATERIALS AND METHODS: Percutaneous nephrolithotomy was performed using adult
      instruments via a 26Fr tract in 23 patients, using pediatric instruments via a
      20Fr tract in 13 and using minimal access (14Fr) in 10. Percutaneous
      nephrolithotomy was performed using general anesthesia with parenteral antibiotic
      prophylaxis. Cystoscopy and retrograde pyelography were performed, and 5Fr to 6Fr
      soft ureteral catheters were placed during each procedure initially. Percutaneous
      access was established via fluoroscopic guidance with the patient in the prone
      position. Pneumatic, ultrasonic and holmium laser lithotriptors were used for in
      situ lithotripsy. A 14Fr nephrostomy catheter was placed at the end of the
      procedure in the 26Fr and 20Fr groups, and in the minimal access group the
      ureteral stent was left indwelling in cases of atraumatic procedure with no
      residual fragments. RESULTS: Mean patient age was 13.2, 5.9 and 6.3 years,
      respectively, in the 26Fr, 20Fr and minimal access groups (p=0.000). Sex
      distribution, previous surgery, stone size, surgery and fluoroscopy times, mean
      hemoglobin decrease and hospitalization time did not differ between the groups.
      However, blood transfusion rate was higher in groups 1 and 2. Stone-free rates
      were 69.5%, 80% and 90%, respectively, in groups 1 to 3. Overall, adjuvant shock
      wave lithotripsy treatment was needed in 3 children. CONCLUSIONS: Smaller
      instrument size to 20Fr did not significantly increase the operative time, and
      resulted in the same success rates as the adult sized devices. However, low blood
      transfusion rates were only reached in the minimal access percutaneous
      nephrolithotomy group.

PMID- 17437839
TI  - Management of multiple failed repairs of the phallus using tissue expanders: long
      term postpubertal results.
AB  - PURPOSE: We present the long-term results of our experience with application of
      tissue expanders for phallic reconstruction in patients with a history of
      multiple surgical repairs. MATERIALS AND METHODS: We retrospectively reviewed the
      medical records of 16 patients who underwent penile tissue expansion for
      treatment of failed phallic reconstruction. The patients were 5 to 22 years old
      (mean age 9.9) at the time of the procedure. The original diagnoses were
      congenital adrenal hyperplasia (1 patient), partial penile amputation (1),
      epispadias (3) and proximal hypospadias (11). We used different shapes and
      numbers of tissue expanders according to the estimated skin augmentation
      requirement for final reconstructive surgery. The injection port was placed at
      the suprapubic area lateral to the penile base, with a small incision between the
      anticipated expander pouch and the reservoir. Penile tissue expanders were
      inflated by injections after 1 to 2 weeks postoperatively. Definitive
      reconstructive surgery was then planned and the tissue expander was removed at
      penile reconstruction at 2 to 11 months (mean 4.6) after implantation. RESULTS:
      Only 1 tissue expander was removed due to erosion. However, sufficient expanded
      skin was available for urethral reconstructions and penile skin coverage in all
      patients (100%). There were 2 cases of overlying penile skin redness, which
      resolved with temporary balloon deflation. Two patients had urethrocutaneous
      fistulas, which were successfully repaired later. Two additional patients
      required meatal dilation/urethromeatoplasty for meatal stenosis. These
      complications were corrected within 1 year postoperatively. After a long-term
      followup of 3 to 10 years (mean 6.5) as patients progressed through puberty, only
      3 had mild chordee. At the end of followup acceptable cosmetic and functional
      results were achieved in 13 patients (81%). CONCLUSIONS: Tissue expansion is
      associated with few complications and good cosmetic results for phallic
      reconstruction in patients with minimal residual skin available for additional
      reconstructive efforts after repeated surgeries.

PMID- 17437840
TI  - Reoperative laparoscopic pyeloplasty in children: comparison with open surgery.
AB  - PURPOSE: We assessed the feasibility of pediatric redo laparoscopic pyeloplasty
      in comparison to redo open pyeloplasty for safety, efficacy, operative time,
      blood loss, postoperative analgesic requirements, length of hospitalization,
      complications, need for readmission and subsequent procedures. MATERIALS AND
      METHODS: We performed a retrospective chart review of consecutive patients
      undergoing reoperative pyeloplasty between June 2003 and July 2006. RESULTS: A
      total of 10 patients (11 redo pyeloplasties) were divided into 2 groups, ie those
      undergoing redo open (4) and laparoscopic (6) pyeloplasty. Groups were similar in
      age, sex, weight, laterality, and number and type of prior interventions to
      repair ureteropelvic junction obstruction. Surgical time for redo laparoscopic
      pyeloplasty was longer than for redo open pyeloplasty (290 vs 203 minutes,
      p<0.05). Success rate was the same in both groups (80%). The redo laparoscopic
      pyeloplasty group had a shorter hospital stay (mean 2.5 vs 4.6 days, p<0.05),
      decreased use of parenteral narcotics (0.2 vs 5 mg/kg, p<0.01), and a trend
      toward decreased oral narcotics (0.2 vs 2.1 mg/kg, p=0.09) and fewer
      complications (0 vs 4, p<0.05). CONCLUSIONS: We confirm the feasibility of redo
      laparoscopic pyeloplasty in the pediatric population. In experienced hands
      pediatric redo laparoscopic pyeloplasty can be performed safely with a success
      rate similar to that of open surgery, and it may provide a faster recovery with
      decreased narcotic requirements and morbidity. Further studies are needed to
      better define the role of laparoscopic pyeloplasty for secondary ureteropelvic
      junction obstruction in the pediatric population.

PMID- 17437841
TI  - Urinary tract infections and bladder dysfunction after renal transplantation in
      children.
AB  - PURPOSE: Urinary tract infection remains a major cause of morbidity in pediatric
      renal transplant recipients. In otherwise healthy children bladder dysfunction
      increases the susceptibility to urinary tract infection. The aims of this study
      were to determine whether bladder dysfunction affects the incidence of urinary
      tract infection after renal transplantation, and to assess the impact of
      recurrent urinary tract infections on graft function. MATERIALS AND METHODS: We
      evaluated bladder function with a questionnaire, uroflowmetry and bladder
      ultrasound, and renal function with clearance of inulin or iohexol (glomerular
      filtration rate) in 68 recipients of renal transplants 5 to 20 years old, at 1 to
      15 years after transplantation, with and without recurrent urinary tract
      infections. RESULTS: Bladder dysfunction was equally common in children with and
      without recurrent urinary tract infections (68% vs 74%, not significant).
      Therefore, it had no effect on the incidence of recurrent urinary tract
      infections. Graft function deteriorated at a faster rate in patients with
      recurrent urinary tract infections than in those without (mean glomerular
      filtration rate 45 vs 57 ml per minute per 1.73 m(2) at 4 years after
      transplantation, p=0.02). CONCLUSIONS: Bladder dysfunction did not predispose
      patients to recurrent urinary tract infections. Graft function declined with time
      in all patients but the rate of deterioration was faster in the group with
      recurrent urinary tract infections.

PMID- 17437842
TI  - Leiomyoma of the urethra and bladder.

PMID- 17437843
TI  - Lower extremity venous obstruction secondary to congenital bladder diverticulum.

PMID- 17437844
TI  - Enhancement of death receptor 4 mediated apoptosis and cytotoxicity in renal cell
      carcinoma cells by subtoxic concentrations of doxorubicin.
AB  - PURPOSE: TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) triggers
      apoptosis in various tumor cells by engaging death receptors 4 and 5. We
      investigated the effect of chemotherapeutic agents on death receptor 4 mediated
      apoptosis in human renal cell carcinoma cells using HGS-ETR1, which is a human
      monoclonal agonistic antibody specific for death receptor 4. MATERIALS AND
      METHODS: Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Synergy was assessed by isobolographic
      analysis. RESULTS: Treatment of the ACHN human renal cell carcinoma cell line
      with HGS-ETR1 combined with 5-fluorouracil, vinblastine or gemcitabine did not
      overcome resistance to these agents. However, treatment with HGS-ETR1 combined
      with doxorubicin had a synergistic cytotoxic effect. Synergy was also achieved in
      another human renal cell carcinoma cell line, Caki-1, and in 5 freshly derived
      renal cell carcinoma cell cultures. A synergistic effect was also observed with
      HGS-ETR1 combined with the doxorubicin derivatives epirubicin, pirarubicin or
      amrubicin. The synergy achieved in cytotoxicity with HGS-ETR1 and doxorubicin was
      also achieved in apoptosis. Sequential treatment with doxorubicin followed by HGS
      ETR1 induced significantly more cytotoxicity than reverse treatment or
      simultaneous treatment (p<0.05). Doxorubicin remarkably increased the cell
      surface expression of death receptor 4 in renal cell carcinoma cells. The
      combination of doxorubicin and HGS-ETR1 significantly activated the caspase
      cascade, including caspase-8, 9, 6 and 3, which are the downstream molecules of
      death receptors. CONCLUSIONS: These findings indicate that doxorubicin sensitizes
      renal cell carcinoma cells to death receptor 4 mediated apoptosis through the
      induction of death receptor 4 and the activation of caspases, suggesting that
      combination therapy of doxorubicin and HGS-ETR1 might be effective as renal cell
      carcinoma therapy.

PMID- 17437846
TI  - Identification of a recurrent t(4;6) chromosomal translocation in prostate
      cancer.
AB  - PURPOSE: We developed and describe a practical method by which primary prostate
      cancer specimens can be screened for recurrent chromosomal translocations, which
      is a potential source of fusion genes, as well as a process by which identified
      translocations can be mapped to define the genes involved. MATERIALS AND METHODS:
      A series of 7 prostate cancer cell lines and 25 transiently established primary
      cell cultures, which were sourced from tissue harvested at 16 radical
      prostatectomies and 9 channel transurethral prostate resections, were screened
      for chromosomal translocations using multiplex-fluorescence in situ hybridization
      technology. A series of fluorescence in situ hybridization based breakpoint
      mapping experiments were performed to identify candidate genes involved in
      regions associated with recurrent translocation. RESULTS: Our analysis identified
      the repetition of 2 translocations in prostate cancer lines, that is t(1;15) and
      t(4;6), at a frequency of 28% and 57%, respectively. More significantly 4 of the
      25 subsequently established primary cultures (16%) also revealed a t(4;6)
      translocation. Using the LNCaP cell line the breakpoints involved were mapped to
      the t(4;6)(q22;q15) region and a number of candidate genes were identified.
      CONCLUSIONS: We found that the t(4;6) translocation is also a repeat event in
      primary cell cultures from malignant prostate cancer. Breakpoint mapping showed
      that the gene UNC5C loses its promoter and first exon as a direct result of the
      translocation in the 4q22 region. As such, we identified it as a possible
      contributor to a putative fusion gene in prostate cancer.

PMID- 17437845
TI  - Adenoviral mediated interferon-alpha 2b gene therapy suppresses the pro
      angiogenic effect of vascular endothelial growth factor in superficial bladder
      cancer.
AB  - PURPOSE: Intravesical adenovirus mediated interferon-alpha gene transfer has a
      potent therapeutic effect against superficial human bladder carcinoma xenografts
      growing in the bladder of athymic nude mice. We determined whether the inhibition
      of angiogenesis might contribute to the antitumor effect. MATERIALS AND METHODS:
      We treated several human urothelial carcinoma cells with adenovirus mediated
      interferon-alpha 2b and monitored its effects on the production of angiogenic
      factors using real-time reverse-transcription polymerase chain reaction, Western
      blotting, and immunohistochemical analysis and a gel shift based transcription
      factor array. To assess the role of adenovirus mediated interferon 2b in
      angiogenic activity we used in vitro invasion assays and evaluated the anti
      angiogenic effects of adenovirus mediated interferon gene therapy in an
      orthotopic murine model of human superficial bladder cancer. RESULTS: In
      adenovirus mediated interferon-alpha infected 253J B-V cells vascular endothelial
      growth factor was decreased and anti-angiogenic interferon-gamma inducible
      protein 10 was up-regulated. In contrast, the addition of as much as 100,000 IU
      recombinant interferon had no apparent effect on vascular endothelial growth
      factor production. Conditioned medium derived from adenovirus mediated interferon
      2b infected 253J B-V cells greatly decreased the invasive potential of human
      endothelial cells and down-regulated their matrix metalloproteinase 2 expression
      compared to controls. Furthermore, adenovirus mediated interferon 2b blocked pro
      angiogenic nuclear signals, such as the transcription factors activating protein
      1 and 2, stimulating protein-1, nuclear factor kappaB and c-myb. In vivo
      experiments revealed significant vascular endothelial growth factor down
      regulation and decreased tumor vessel density in the adenovirus mediated
      interferon 2b treated group compared to controls. CONCLUSIONS: Treatment with
      adenovirus mediated interferon 2b increases the angiostatic activity of the
      bladder cancer microenvironment. This inhibition may prove beneficial for
      treating superficial bladder cancer with adenovirus mediated interferon-alpha and
      hopefully contribute to a decreased recurrence rate of this neoplasm.

PMID- 17437847
TI  - Increased expression of cyclooxygenase-2 correlates with resistance to radiation
      in human prostate adenocarcinoma cells.
AB  - PURPOSE: Cyclooxygenase-2 functions as a survival factor by protecting cells from
      apoptosis. We analyzed cyclooxygenase-2 expression in LNCaP-COX-2 and LNCaP-Neo
      cell lines treated with irradiation. MATERIALS AND METHODS: LNCaP-COX-2 and LNCaP
      Neo cells were treated with 0 to 500 microM celecoxib and a dose response curve
      was generated. A clonogenic assay was performed in which cells were subjected to
      irradiation (0 to 6 Gy) with or without celecoxib. Cyclooxygenase-2 protein and
      other relevant proteins were measured by immunohistochemistry Western blot
      analysis after irradiation and celecoxib treatment. RESULTS: The 2 studied cell
      lines experienced cytotoxic effects of celecoxib in a dose related manner.
      Clonogenic assays demonstrated that LNCaP-COX-2 cells were significantly more
      resistant to radiation therapy than LNCaP-Neo cells. Furthermore, the addition of
      celecoxib sensitized LNCaP-Neo and LNCaP-COX-2 cells to the cytocidal effects of
      radiation. Moreover, cyclooxygenase-2 over expression was associated with the
      over expression of pAkt and carbonic anhydrase. In this cell line irradiation
      alone was associated with increased expression of cyclooxygenase-2 and carbonic
      anhydrase. Combination therapy with irradiation and celecoxib down-regulated
      cyclooxygenase-2, pAKT and carbonic anhydrase. LNCaP-Neo cells expressed carbonic
      anhydrase and pAkt. Irradiation of these cells increased carbonic anhydrase and
      pAkt expression. Combination therapy with irradiation and celecoxib down
      regulated carbonic anhydrase and pAkt. CONCLUSIONS: Cyclooxygenase-2 expression
      is also associated with pAkt and carbonic anhydrase expression. Down-regulation
      of cyclooxygenase-2 by celecoxib is associated with decreased expression of
      cyclooxygenase-2, pAkt and carbonic anhydrase, and eventual radiation
      sensitization, which is a phenomenon that may have clinical usefulness.

PMID- 17437848
TI  - The expression and function of androgen receptor coactivator p44 and protein
      arginine methyltransferase 5 in the developing testis and testicular tumors.
AB  - PURPOSE: The role of androgen receptor coactivators in testicular development and
      cancer formation is unclear. p44/Mep50 was identified as an androgen receptor
      coactivator that functions in a complex with protein arginine methyltransferase
      5. We studied the expression of p44 and protein arginine methyltransferase 5 in
      developing fetal testis and adult testicular tumors, including seminomas and
      Leydig cell tumors. MATERIALS AND METHODS: A total of 30 human fetal testes from
      abortuses at a gestational age of 10 to 40 weeks, 33 human seminomas and 11 human
      Leydig cell tumors were retrieved from the archives of the departments of
      pathology. Immunohistochemistry was performed with affinity purified p44 and IgG
      purified protein arginine methyltransferase 5 polyclonal antibodies. RESULTS:
      Protein arginine methyltransferase 5 and p44 were expressed predominantly as
      nuclear proteins in fetal Leydig cells and human adult nonneoplastic testes,
      including germ cells and Leydig cells, while they were expressed in the cytoplasm
      of germ cells of the fetal testis. Expression was strongest in the fetal testis
      during the second trimester. Compared to adult nonneoplastic testes, human
      seminoma and Leydig tumor cells showed a marked decrease in nuclear expression of
      p44 and protein arginine methyltransferase 5 with a concomitant marked increase
      in cytoplasmic expression of these proteins. Furthermore, average testicular size
      was increased by 29% in p44(+/-) heterzygotic mice. CONCLUSIONS: These results
      suggest distinct functions of the nuclear and the p44/protein arginine
      methyltransferase 5 complexes in the developing fetal testis and in the
      oncogenesis of testicular tumors. Further studies are needed to confirm the
      functional relevance of these findings.

PMID- 17437849
TI  - Diamond-like carbon coatings on ureteral stents--a new strategy for decreasing
      the formation of crystalline bacterial biofilms?
AB  - PURPOSE: Any catheter material placed in the urinary tract provides a surface for
      bacterial colonization and, therefore, it is susceptible to encrustation with
      crystalline bacterial biofilm. Encrustation and blockage by biofilms remain a
      major complication in patient care. Most patients with indwelling ureteral stents
      experience irritative symptoms related to these implants and many experience
      discomfort. MATERIALS AND METHODS: Plasma deposited diamond-like amorphous carbon
      coatings are well-known for their excellent biocompatibility. A low temperature,
      low pressure plasma enhanced chemical vapor deposition technology was developed
      especially for coating polymeric medical implants with diamond-like carbon. We
      investigated the ability of diamond-like carbon to decrease the formation of
      crystalline bacterial biofilm as well as stent related side effects and
      discomfort. Diamond-like carbon coated ureteral Double-J stents were tested in
      vivo. RESULTS: In 10 patients with heavy encrustation, different underlying
      diseases and a stent removal frequency of less than 6 weeks due to encrustation a
      total of 26 diamond-like carbon coated stents were successfully tested for their
      ability to decrease the extent of crystalline biofilm formation. There was a
      2,467-day period of experience with diamond-like carbon coated stents. No
      primarily stent related complications occurred. No crystalline biofilm formation
      was observed in vivo. Excellent and facile handling, a less painful replacement
      procedure and high tolerance of application were reported by physicians and
      patients. Due to low friction the coated stents could be placed and removed much
      more easily than standard stents. The frequency and severity of symptomatic
      urinary tract infections were distinctly decreased. CONCLUSIONS: Diamond-like
      carbon coating is a new strategy to improve the surface properties of ureteral
      stents. This novel surface effectively decreases friction, encrustation
      tendencies and biofilm formation.

PMID- 17437850
TI  - The protective role of heme oxygenase-1 induction on testicular tissues after
      testicular torsion and detorsion.
AB  - PURPOSE: Testicular torsion-detorsion has been identified as an ischemia
      reperfusion type of injury. We elucidated the protective role of heme oxygenase-1
      super induction on testicular torsion-detorsion injury. MATERIALS AND METHODS:
      Adult male Sprague-Dawley rats were randomly allocated to undergo testicular
      torsion-detorsion, immediately followed by injection of normal saline, the heme
      oxygenase-1 inducer hemin or hemin plus the heme oxygenase-1 inhibitor tin
      protoporphyrin. Another set of rats that underwent sham operation, immediately
      followed by injection of normal saline, hemin or hemin plus tin protoporphyrin,
      served as controls. Testes were harvested 4 and 24 hours after detorsion,
      respectively, in the experimental groups or at comparable time points in the
      control groups. RESULTS: Histological evaluation confirmed that torsion-detorsion
      caused significant testicular tissue injury. Torsion-detorsion also caused
      significant increases in the testicular levels of nitric oxide, malondialdehyde,
      myeloperoxidase activity and heme oxygenase-1. The heme oxygenase-1 inducer hemin
      significantly enhanced the heme oxygenase-1 expression induced by torsion
      detorsion and in turn attenuated testicular injury, and increases in nitric
      oxide, malondialdehyde and myeloperoxidase activity. In addition, the protective
      effects of hemin were significantly offset by the heme oxygenase-1 inhibitor tin
      protoporphyrin. CONCLUSIONS: Super induction of heme oxygenase-1 protects testes
      from torsion-detorsion injury.

PMID- 17437851
TI  - Local and systemic effects of endoluminal pelvic perfusion of isoproterenol: a
      dose response investigation in pigs.
AB  - PURPOSE: Isoproterenol (Sygehus Apotekerne Danmark, Copenhagen, Denmark) is a
      beta-adrenergic agonist known to cause upper urinary tract relaxation. We studied
      the local effect on pelvic pressure and the systemic effects of endoluminal
      perfusion with isoproterenol in a porcine model. MATERIALS AND METHODS: Pigs
      weighing 40 kg were studied. Catheters were placed in the renal pelvis for
      pressure measurement and perfusion, and a catheter was used to drain the bladder.
      Blood pressure and heart rate were recorded. In 6 pigs in group 1 the pelvic
      pressure increase was examined at increasing flow rates of 0, 2, 5, 8, 10 and 15
      ml per minute with saline containing 0, 10(-3), 10(-2), 10(-1), 1 and 10
      microg/ml isoproterenol. Blood values of isoproterenol were analyzed. In 6 pigs
      in group 2 the pelvis was perfused at a flow rate of 8 ml per minute with saline
      containing 0, 10(-5), 10(-4), 10(-3), 10(-2), 10(-1), 1 and 10 microg/ml
      isoproterenol. RESULTS: In group 1 endoluminal perfusion with isoproterenol
      inhibited the pelvic pressure increase due to perfusion at all concentrations of
      isoproterenol. At a perfusion rate of 8 ml per minute the maximal effect (a 78%
      decrease) was achieved using 0.1 microg/ml isoproterenol without cardiovascular
      side effects. In group 2 all isoproterenol concentrations caused significant
      inhibition of the pressure-flow relationship in a dose dependent matter. A 64%
      decrease in the pressure increase due to saline perfusion was achieved at 0.1
      microg/ml isoproterenol without concomitant significant cardiovascular side
      effects. Isoproterenol was only detected in plasma during perfusion with 1 and 10
      microg/ml isoproterenol, which caused significant cardiovascular side effects in
      the latter case. CONCLUSIONS: Isoproterenol significantly inhibits the pressure
      increase due to perfusion in the normal porcine renal pelvis without concomitant
      cardiovascular side effects. Isoproterenol is a safe drug in this porcine model
      and, hence, it is potentially useful during endourological procedures.

PMID- 17437852
TI  - Up-regulation of estrogen responsive genes in hypospadias: microarray analysis.
AB  - PURPOSE: An unexplained increase in the incidence of hypospadias has been
      reported, and yet to our knowledge the molecular events and their regulation
      leading to hypospadias remain unknown, although environmental compounds capable
      of endocrine activity are suspected. We screened on a global scale abnormalities
      in gene expression in human hypospadiac tissue compared to those in
      nonhypospadiac tissue. Additionally, microarray analysis of tissue from a pair of
      fraternal twins, including 1 with and 1 without hypospadias, served as a control
      for genetic variability. We hypothesized that gene expression would differ
      between hypospadiac vs nonhypospadiac tissue and fraternal twin data would show
      patterns similar to those of group data on hypospadiac and nonhypospadiac tissue.
      MATERIALS AND METHODS: Microarray analysis was performed on tissue from patients
      with and without hypospadias, and from a pair of fraternal twins, including 1
      with and 1 without hypospadias. Analysis incorporated the expression of 22,000
      genes. RESULTS: We found significant differences in gene expression, specifically
      with a group of genes, including CYR61, CTGF, ATF3 and GADD45beta, known to be
      responsive to estrogen or to interact with estrogen receptor. CONCLUSIONS: Our
      findings provide support for the hypothesis that endocrine active environmental
      compounds may contribute to the development of hypospadias. Additionally,
      regulation of these genes may have a role in formation of the urethra.

PMID- 17437853
TI  - Novel mutations involving the INSL3 gene associated with cryptorchidism.
AB  - PURPOSE: Cryptorchidism affects 1% to 9% of full-term male neonates. Hypospadias
      is the second most frequent congenital anomaly seen in newborn males. These
      pathological conditions are part of the testicular dysgenesis syndrome. Insulin
      like factor 3 and LGR8 (leucine-rich repeat-containing G protein-coupled receptor
      8), acting as a hormone and a receptor, respectively, are involved in control of
      the first phase of testicular descent via gubernacular development. MATERIALS AND
      METHODS: The study group consisted of 184 patients, of whom 52 presented with
      unilateral cryptorchidism, 37 presented with bilateral cryptorchidism, 19
      presented with cryptorchidism and hypospadias, 1 presented with bilateral
      cryptorchidism and micropenis, and 75 presented with isolated hypospadias. A
      control panel consisted of 270 controls, including 127 fertile, and 143 fertile
      noncryptorchid males. Insulin-like factor 3 mutations were analyzed by direct
      sequencing and restriction enzyme digestion. We analyzed the ability of the
      mutant insulin-like factor 3 peptides identified in this study to activate LGR8
      receptor in an ex vivo assays. RESULTS: We identified 3 novel insulin-like factor
      3 variants, including C-19G, V18M and R105H, in 3 of the 109 patients (2.75%) but
      in none of the 270 controls. The V18M mutation in the insulin-like factor 3
      signal peptide had a significant deleterious effect in activating LGR8 receptor
      in ex vivo studies (p<0.05). To our knowledge we report the first variant in the
      promoter region of the insulin-like factor 3 gene in a patient with
      cryptorchidism in association with micropenis. CONCLUSIONS: Mutations involving
      the insulin-like factor 3 gene may contribute to other anomalies of male genital
      development, such as micropenis.

PMID- 17437854
TI  - Re: The epidemiology of renal cell carcinoma.

PMID- 17437855
TI  - Re: The interpretation of serum prostate specific antigen in men receiving 5alpha
      reductase inhibitors: a review and clinical recommendations.

PMID- 17437857
TI  - Re: Long-term follow-up and clinical characteristics of testicular Leydig cell
      tumor: experience with 24 cases.

PMID- 17437858
TI  - Re: Neurological bypass for sensory innervation of the penis in patients with
      spina bifida.

PMID- 17437860
TI  - Re: Choices.

PMID- 17437861
TI  - The role of KIT in the management of patients with gastrointestinal stromal
      tumors.
AB  - In recent years, immunohistochemical staining for KIT (CD117) has become integral
      to the diagnosis of gastrointestinal stromal tumors (GISTs), nearly 90% of which
      harbor activating mutations in the KIT receptor tyrosine kinase gene.
      Approximately 80% of patients with metastatic GIST show at least some clinical
      response to the targeted small molecule KIT inhibitor imatinib. The response to
      imatinib is closely correlated with the presence and type of KIT mutation. GISTs
      with the most common KIT exon 11 mutations have the highest response rate by far,
      whereas GISTs lacking mutations in KIT or the alternative receptor tyrosine
      kinase PDGFRA show much lower rates of response to imatinib. Less than 5% of
      GISTs are KIT-immunonegative; and many of these tumors have activating mutations
      of PDGFRA, some of which are also inhibited by imatinib. Most patients who
      initially respond to imatinib become resistant and eventually progress, which
      coincides with the selection of imatinib-resistant secondary KIT mutations in the
      kinase domain. Sunitinib has recently been approved for patients with GIST,
      principally those who fail imatinib therapy; and additional small molecule
      inhibitors are in the pipeline. It is becoming evident that alternative
      approaches to direct KIT inhibition will be required for long-term survival of
      patients with advanced GISTs. This review examines the role of KIT in the
      diagnosis and management of patients with GIST.

PMID- 17437862
TI  - "Med-X": a medical examiner surveillance model for bioterrorism and infectious
      disease mortality.
AB  - We created a model surveillance system (Med-X) designed to enable medical
      examiners and coroners to recognize fatal infections of public health importance
      and deaths due to bioterrorism. All individuals who died in New Mexico and fell
      under medical examiner jurisdiction between November 23, 2000, and November 22,
      2002, were prospectively evaluated using sets of surveillance symptoms and
      autopsy-based pathologic syndromes. All infectious disease deaths were evaluated
      to identify the specific causative agent. Of 6104 jurisdictional cases, 250
      (4.1%) met Med-X criteria, of which 141 (56.4%) had a target pathologic syndrome.
      Ultimately, 127 (51%) of the 250 cases were due to infections. The causative
      organism was identified for 103 (81%) of the infectious disease deaths, of which
      60 (58.3%) were notifiable conditions in New Mexico. Flu-like symptoms, fever and
      respiratory symptoms, and encephalopathy or new-onset seizures had predictive
      values positive for fatal infections of 65%, 72%, and 50%, respectively, and are
      useful as autopsy performance criteria. Before the development of surveillance
      criteria, 37 (14.8%) of the cases ordinarily would not have been autopsied
      resulting in a 1% increase in autopsy workload. Med-X is an effective method of
      detecting infectious disease deaths among medical examiner cases. Uniform
      criteria for performing medical examiner autopsies and reporting cases to public
      health authorities enhance surveillance for notifiable infectious diseases and
      increase the likelihood of recognizing deaths related to bioterrorism.

PMID- 17437863
TI  - The root and root canal morphology of the human mandibular first premolar: a
      literature review.
AB  - The purpose of this study was to undertake a comprehensive literature review of
      the root and root canal morphology of the mandibular first premolar. Published
      studies citing the anatomy and morphology of mandibular premolars report data for
      over 6,700 teeth. These studies were divided into anatomical studies reporting
      number of roots, number of canals, and apical morphology. Variations because of
      sex and ethnic background have also been reported, along with case reports of
      anomalies. Approximately 98% of the teeth in these studies were single-rooted.
      The incidence of two roots was 1.8%. Three roots when reported were found in 0.2%
      of the teeth studied. Four roots were rare and were found in less than 0.1% of
      the teeth studied. Studies of the internal canal morphology revealed that a
      single canal was present in 75.8% of the teeth. Two or more canals were found in
      24.2% of the teeth studied. A single apical foramen was found in 78.9% of the
      teeth, whereas 21.1% had two or more apical foramina. The role of genetics and
      racial variation may result in differences of incidence of root number and canal
      number in human populations. The dental literature is not unique in studying
      ethnicity and sex variations. Higher incidences of teeth with additional canals
      and roots have been reported in Chinese, Australian, and sub-Sahara African
      populations. Physical anthropology studies seem to show the lowest incidence in
      Western Eurasian, Japanese and American Arctic populations. The root and root
      canal morphology of this tooth can be complex and requires careful evaluation
      prior to root canal therapy.

PMID- 17437864
TI  - The C-shaped root canal configuration: a review.
AB  - Recognition of unusual variations in the canal configuration is critical because
      it has been established that the root with a single tapering canal and apical
      foramen is the exception rather than the rule. The early recognition of these
      configurations facilitates cleaning, shaping, and obturation of the root canal
      system. "C" configuration, which is an important anatomic variation, presents a
      thin fin connecting the root canals. Because of the importance of its true
      diagnosis and treatment, a comprehensive review of published information and
      investigations about it in addition to approaches for its treatment is necessary.

PMID- 17437865
TI  - Vascular endothelial growth factor and its relationship with the dental pulp.
AB  - The dental pulp is a loose connective tissue located within rigid dentinal walls.
      Therefore, when subjected to a stimulus, the pulpal tissue has little expansion
      capacity. The defense mechanisms of this tissue include the formation of tertiary
      dentin as well as the production of signaling molecules that help in the repair.
      The dentin matrix is rich in growth factors (GFs) that, when diluted and diffused
      into the pulp tissue, aid the healing process of the dentinopulpar complex. The
      angiogenic GFs participate in this event. Vascular endothelial growth factor
      (VEGF), a potent mitogen for endothelial cells, promotes endothelial cell
      survival and angiogenesis. Among its receptors, VEGFR-2 seems to be the most
      intimately associated with mitogenic activities, cell migration, vascular
      permeability, and survival of endothelial cells. This literature review addresses
      the cell-signaling process that occurs in response to a pulp stimulus up to its
      transduction in the target cell, describing the VEGF, as well as its
      characteristics and receptors. The reported studies have correlated the
      expression of VEGF and its potential functions that may have an impact on several
      dental specialties, thus indicating that further clinical investigations should
      be conducted in order to translate the results obtained until this moment
      primarily in laboratory experiments.

PMID- 17437866
TI  - Comparison of electrical, thermal, and pulse oximetry methods for assessing pulp
      vitality in recently traumatized teeth.
AB  - Pulse oximeter is a well-established and noninvasive method for measuring
      vascular health by evaluating oxygen saturation. This study compared the efficacy
      of a custom-made pulse oximeter dental probe with the electric pulp testing and
      thermal testing for measuring pulp vitality status of recently traumatized
      permanent teeth. Readings for pulp vitality for 17 recently traumatized maxillary
      incisors were taken with custom-made pulse oximeter dental probe (group 1),
      electrical pulp tester (group 2), and thermal testing (group 3) over a 6-month
      period. The proportion of recently traumatized teeth showing a positive
      responsiveness in thermal/electric pulp tests increased from no teeth showing
      responsiveness on day 0 to 29.4% teeth on the 28th day, 82.35% of teeth at 2
      months, and 94.11% teeth at 3 months. However, pulse oximeter gave positive
      vitality readings that remained constant over the study period from day 0 to 6
      months in all patients.

PMID- 17437867
TI  - Detection and eradication of microorganisms in root-filled teeth associated with
      periradicular lesions: an in vivo study.
AB  - This study determined the presence of microorganisms by culture and polymerase
      chain reaction in asymptomatic root-filled teeth with periradicular lesions.
      Furthermore, a disinfecting regimen using sodium hypochlorite (NaOCl),
      ethylenediaminetetraacetic acid (EDTA), chlorhexidine digluconate (CHX)
      irrigation, and calcium hydroxide (Ca(OH)(2)) dressing was assessed. After
      removal of the root-filling material, specimens of 20 cases undergoing
      retreatment were sampled. Moreover, the canals were sampled after each step of
      the disinfecting regimen. Prevalence of microorganisms was 60% by culture and 65%
      by polymerase chain reaction. In four of those samples (31%), DNA of Enterococcus
      faecalis was found. After further root canal preparation and irrigation using
      NaOCl and EDTA, microorganisms could be detected in none of the teeth. Thus, CHX
      and Ca(OH)(2) could not show further disinfection. In contrast, microorganisms
      were found in two teeth after the interappointment dressing. It may be concluded
      that proper root canal preparation and irrigation using NaOCl and EDTA are
      sufficient for decontamination of the root canal system during endodontic
      retreatment.

PMID- 17437868
TI  - Reduction in the cultivable bacterial populations in infected root canals by a
      chlorhexidine-based antimicrobial protocol.
AB  - The present clinical study was conducted to assess the bacterial reduction after
      chemomechanical preparation using 0.12% chlorhexidine digluconate solution as an
      irrigant and the additive antibacterial effect of intracanal dressing with
      calcium hydroxide (Ca(OH)(2)) associated with 0.12% chlorhexidine digluconate
      gel. According to stringent inclusion/exclusion criteria, 13 teeth with primary
      intraradicular infections and chronic apical periodontitis were selected and
      followed in the study. Bacterial samples were taken at the baseline (before
      treatment) (S1), after chemomechanical preparation using chlorhexidine (CHX) as
      an irrigant (S2), and after a 7-day dressing with Ca(OH)(2)/CHX paste (S3).
      Cultivable bacteria recovered from infected root canals at the three stages were
      counted and identified by means of 16S ribosomal RNA gene sequencing analysis. At
      S1, all canals were positive for bacteria, with the mean number of 3.5 taxa per
      canal (range, 2-9). At S2, 7 cases (53.8%) still harbored cultivable bacteria,
      with a mean number of 1.7 taxon per canal (range, 1-4). At S3, only one case
      (7.7%) was positive for the presence of bacteria. The great majority of taxa
      found in posttreatment samples were gram-positive bacteria. A significantly high
      reduction in bacterial counts was observed between S1 and S2 and S1 and S3
      (p<0.001). Also, significant differences were observed for comparisons involving
      S2 and S3 samples with regard to both quantitative bacterial reduction (p=0.014)
      and number of cases yielding negative cultures (p=0.01). It was concluded that
      chemomechanical preparation with 0.12% CHX solution as an irrigant significantly
      reduced the number of intracanal bacteria but failed to render the canal free of
      cultivable bacteria in about one half of the cases. Application of a 7-day
      intracanal dressing with Ca(OH)(2)/CHX paste further increased significantly the
      number of cases yielding negative cultures.

PMID- 17437869
TI  - An investigation into differential diagnosis of pulp and periapical pain: a
      PennEndo database study.
AB  - Nine hundred fifty-one emergency and 997 nonemergency patients seeking endodontic
      treatment were the basis of this study. Variables of interest were 10 pain
      descriptors, percussion and palpation tests, causative factors, and paired pulpal
      and periapical diagnoses. A higher number of patients suffering from symptomatic
      pulpal conditions sought emergency care. Odds of caries being a causative factor
      were high in symptomatic pulps compared with asymptomatic pulpal and periapical
      conditions. Higher odds ratios were obtained for sharp pain in symptomatic pulps
      versus symptomatic periapical conditions. Conversely, odds ratios for dull pain
      were higher in symptomatic periapical conditions compared with asymptomatic
      periapical conditions. Percussion and palpation tests were significant in
      differentially diagnosing between pulpal and periapical conditions. In
      conclusion, caries was associated with painful pulpitis. The results confirm the
      differential diagnostic power of sharp and dull pain and percussion and palpation
      tests. Several symptoms previously believed to have differential diagnostic power
      were found insignificant.

PMID- 17437870
TI  - The incidence of mechanical allodynia in patients with irreversible pulpitis.
AB  - The mechanisms of odontogenic pain are complex and incompletely understood. Cases
      of irreversible pulpitis are thought to represent a localized inflammatory
      response to bacterial challenge in dental pulp tissue. The presenting symptoms
      are classically defined by exaggerated painful episodes to thermal stimuli that
      may linger after cessation of the stimulus. However, the associated incidence of
      mechanical allodynia, defined as reduced mechanical pain threshold to masticatory
      forces, has not been characterized. This study evaluated pain intensity ratings
      and the presence of mechanical allodynia reported by 993 consecutive dental
      patients presenting for tooth extraction in a community health center. After
      clinical and radiographic examinations, the pulpal/periradicular diagnostic
      categories were normal pulp/normal periradicular (n=792 patients), irreversible
      pulpitis/normal periradicular (n=86), or irreversible pulpitis/acute
      periradicular periodontitis (n=115). The rank order for the mean values of pain
      intensity ratings was irreversible pulpitis/acute periradicular periodontitis >
      irreversible pulpitis/normal periradicular > normal/normal (p<0.05 for all
      comparisons). The incidence of mechanical allodynia in patients presenting with
      irreversible pulpitis was 57.2%, indicating that periradicular mechanical
      allodynia contributes to early stages of odontogenic pain because of inflammation
      of vital pulpal tissue.

PMID- 17437871
TI  - In vitro activity of amoxicillin, clindamycin, doxycycline, metronidazole, and
      moxifloxacin against oral Actinomyces.
AB  - Actinomyces spp have been increasingly associated with endodontic infections.
      However, the antimicrobial susceptibility of this genus has not been studied
      extensively. The objective of this study was to determine the susceptibility of
      oral isolates of Actinomyces naeslundii, Actinomyces gerencseriae, Actinomyces
      israelii, Actinomyces viscosus, and Actinomyces odontolyticus to amoxicillin,
      clindamycin, doxycycline, metronidazole, and moxifloxacin using in vitro assays.
      The minimum inhibitory concentration (MIC) of each bacterial isolate was
      determined by using E-test strips (AB Biodisk, Solna, Sweden). The MIC(90) was
      0.19 microg/mL for amoxicillin, 0.25 microg/mL for doxycycline, 0.50 microg/mL
      for moxifloxacin, and 1.00 microg/mL for clindamycin. However, metronidazole was
      not active against any of the Actinomyces spp tested (MIC(90)>256 microg/mL).

PMID- 17437872
TI  - The influence of root canal sealer on extended intracanal survival of
      Enterococcus faecalis with and without gelatinase production ability in obturated
      root canals.
AB  - Enterococcus faecalis can survive for extended periods in obturated root canals.
      In this study, the hypotheses tested were that long-term survival of E. faecalis
      is dependent on (1) the type of endodontic sealer and (2) the capacity for
      microbial gelatinase activity, a potential "virulence" trait identified
      previously in clinical isolates. Root canals of extracted human canines (n=95)
      were inoculated with either E. faecalis OG1RF or its gelatinase-negative mutant
      E. faecalis TX5128. After 48 hours of incubation at 37 degrees C, canals were
      obturated with gutta-percha and either the epoxy-resin-based AH-Plus (Dentsply,
      De Trey, Konstanz, Germany), the silicone-based RoekoSeal (Coltene/Whaledent,
      Langenau, Germany), or zinc oxide eugenol-based Roth's sealer (Root Canal Cement
      Type 801; Roth International Ltd, Chicago, IL). Access cavities were sealed.
      After 8 months of incubation at 37 degrees C, viable E. faecalis was recovered
      from more teeth sealed with RoekoSeal (95%) compared with AH-Plus (40%)
      (p=0.0004, Fisher's exact test) and Roth's sealer (45%) (p=0.0012, Fisher's exact
      test). In the RoekoSeal groups, viable counts of E. faecalis OG1RF were higher
      than E. faecalis TX5128 (p=0.03, Mann-Whitney U test) suggesting that gelatinase
      activity plays a role in long-term survival of E. faecalis in obturated root
      canals.

PMID- 17437873
TI  - An in vitro comparison of the antimicrobial effects of various endodontic
      medicaments on Enterococcus faecalis.
AB  - The purpose of this in vitro study was to investigate the antimicrobial action of
      Dermacyn (Oculus Innovative Sciences, Petaluma, CA), BioPure MTAD (Dentsply Tulsa
      Dental, Johnson City, TN), 2% chlorhexidine (CHX; Ultradent, West Jordan, UT),
      and 5.25% sodium hypochlorite (NaOCl) against Enterococcus faecalis (American
      Type Culture Collection 4082). Eighteen Petri dishes of BHI agar were inoculated
      with E faecalis. Each Petri dish had five saturated paper disks placed. Four of
      the disks were saturated with a different test solution, and the last paper disk
      served as the control and was saturated with sterile distilled water. The plates
      were randomly distributed into two groups. Group one (n=9) was incubated
      aerobically and group 2 (n=9) was incubated anaerobically for 48 hours at 37
      degrees C. The largest diameter of the zones of microbial inhibition was measured
      in millimeters and recorded. Statistical analysis was performed with repeated
      measures analysis of variance. BioPure MTAD showed significantly (p<0.05) more
      zones of microbial inhibition than 5.25% NaOCl, 2% CHX, and Dermacyn. Sodium
      hypochlorite and CHX showed significantly (p<0.05) more zones of microbial
      inhibition than Dermacyn. The zone of inhibition between NaOCl and CHX was not
      significant (p>0.05). The control group showed no microbial inhibition.

PMID- 17437874
TI  - Effect of propolis on survival of periodontal ligament cells: new storage media
      for avulsed teeth.
AB  - Propolis is a multifunctional material used by bees in the construction and
      maintenance of their hives. Propolis possesses several biologic activities such
      as anti-inflammatory, antibacterial, antioxidant, antifungal, antiviral, and
      tissue regenerative, among others. The purpose of this study was to determine the
      ability of propolis to serve as a temporary storage medium for the maintenance of
      periodontal ligament (PDL) cell viability of avulsed teeth. PDL cells were
      obtained from healthy third molars and cultured in Dulbecco's Modified Eagles
      Medium (DMEM). Cultures were subjected to 10% propolis solution, 20% propolis
      solution, long-shelf life light milk with lower fat content (milk), Hank's
      Balanced Salt Solution, tap water as the negative control, and DMEM as the
      positive control. Tissue culture plates were incubated with experimental media at
      37 degrees C for 1, 3, 6, 12, or 24 hours. PDL cell viability was assessed by
      trypan blue exclusion. Statistical analysis of the data was accomplished by using
      one-way analysis of variance complemented by the Tukey test. The level of
      significance was 5% (p<0.05). The results showed that 10% propolis was a more
      effective storage medium than other groups. In conclusion, propolis can be
      recommended as a suitable transport medium for avulsed teeth.

PMID- 17437875
TI  - Performance of ultrasonic retrograde systems.
AB  - The aim of this study was to evaluate variations in power output of different
      Piezon-Master 400 (Electro Medical Systems, Nyon, Switzerland) ultrasonically
      driven generators and analytic handpieces at a range of power settings. A
      scanning laser vibrometer was used to measure the maximum vibration displacement
      amplitude of a KiS 2D tip. Ten repeat scans were made of the unloaded tip
      oscillation at six power settings. Data were acquired from four different
      generators and handpieces. Linear trend lines fitted to all tip data showed that
      none of the generator/handpiece combinations produced a linear increase in tip
      displacement amplitude with increasing power setting. A univariate analysis of
      variance (general linear model) showed that generator, handpiece, and power were
      all significant variables (p<0.0001). This study showed that there is significant
      variability in the power output between generators, and not all Analytic
      handpieces performed consistently when compared with each other.

PMID- 17437876
TI  - Comparison of passive ultrasonic debridement between fluted and nonfluted
      instruments in root canals.
AB  - The purpose of this study was to determine if passive ultrasonic irrigation using
      finger spreaders was more effective than standard files in removing debris after
      root canal instrumentation. Eighty-five straight canals were instrumented and
      then passively ultrasonically irrigated with either fluted files or nonfluted
      finger spreaders for 3 minutes or 1 minute. Images of split canal lumens were
      imported into Adobe Photoshop CS2 (Adobe Systems, San Jose, CA), and percentage
      of debris remaining was calculated. Analysis of variance and Student Newman-Keuls
      post hoc tests (p<0.05) showed that when comparing the entire canal, 3 minutes of
      activation with a file had significantly less debris remaining than 1 minute of
      activation with a spreader. There was a trend for 1 minute of activation with a
      file to have less debris than either 3 minutes or 1 minute of activation with a
      spreader. When comparing apical, middle, or coronal thirds between groups, no
      significant differences were found. The use of a nonfluted spreader did not
      improve debris removal.

PMID- 17437877
TI  - Calcium loss from root canal dentin following EDTA, EGTA, EDTAC, and tetracycline
      HCl treatment with or without subsequent NaOCl irrigation.
AB  - The aim of this study was to determine the extent of calcium removal on root
      canal dentin after 17% EDTA, 17% EGTA, 15% EDTAC, and 1% tetracycline-HCl
      treatment; with or without subsequent use of 2.5% NaOCl. Extracted single-rooted
      human teeth were bisected longitudinally and the root halves (n=100) were
      isolated with nail varnish, leaving the root canal exposed. The samples were
      immersed in the test solutions for 1 and 5 minutes, after which the amount of
      calcium ion (Ca(2+)) release into the solutions was determined by flame
      photometry. Regardless of treatment time, all single (treatment solution only)
      and combined (treatment solution with subsequent NaOCl application) irrigation
      regimens removed significantly more Ca(2+) than control treatment (distilled
      water). Compared with other groups, treatment with 17% EDTA and 17% EDTA + 2.5%
      NaOCl resulted in the maximum amount of Ca(2+) removal from root canal dentin
      (p<0.05). All combined-treatment groups except 17% EGTA + 2.5% NaOCl removed
      significantly more Ca(2+) than their single-treatment versions (p<0.05). Within
      each test group, extending the treatment time to 5 minutes resulted in
      significantly more Ca(2+) removal (p<0.05).

PMID- 17437878
TI  - Evaluation of the efficiency of a new file removal system in comparison with two
      conventional systems.
AB  - A novel file-removal system (FRS) was designed to address weak points of
      conventional file-removal methods. The purpose of this study was to compare file
      removal time and dentin removal rates among the FRS, the Masserann kit (Micro
      Mega, Besancon, France), and an ultrasonic file-removal method. Ninety extracted
      mandibular incisors with separated nickel titanium files were divided into 3
      groups of 30 teeth each. Groups 1, 2, and 3 had file-removal attempts made by
      using the Masserann kit, a CPR-7 titanium ultrasonic tip (Obtura-Spartan Corp.,
      Fenton, MO), and the FRS, respectively. Each group had three operators removing
      the separated files. Pre-/postoperative digital radiographs were downloaded into
      image analyzing software that calculated the amount of dentin removed. The FRS
      needed less time and had less dentin loss than the others (p<0.05). There were
      statistical differences between the experienced operator and less experienced
      operators regarding the file-removal time and the dentin removal rates (p<0.05).

PMID- 17437879
TI  - Effect of immersion in sodium hypochlorite on torque and fatigue resistance of
      nickel-titanium instruments.
AB  - This study investigated the effect of immersion in sodium hypochlorite (NaOCl) on
      torque and fatigue resistance of two nickel-titanium files. Size 25 .04 ProFile
      and RaCe files were immersed in 5.25% NaOCl for 1 or 2 hours at temperatures of
      21 degrees C and 60 degrees C. Torque and angle at failure were measured
      according to ISO 3630-1. Resistance to cyclic fatigue was determined by counting
      rotations to breakage in a 90 degrees curve with a 5-mm radius. Data were
      analyzed by 2-way analysis of variance. Torsional resistance of both rotaries was
      not significantly affected by immersion in NaOCl, except after 2 hours of
      immersion at 60 degrees C. Resistance to cyclic fatigue decreased significantly
      for ProFile and RaCe instruments after immersion in NaOCl. Spontaneous fractures
      occurred in 28 of 160 files during immersion in NaOCl. In conclusion, nickel
      titanium rotaries have reduced resistance to cyclic fatigue after contact with
      heated NaOCl and may then be considered single-use instruments.

PMID- 17437880
TI  - Effects of short-term chemical disinfection of gutta-percha cones: identification
      of affected microbes and alterations in surface texture and physical properties.
AB  - The aims of this study were to identify microorganisms on the surface of gutta
      percha (GP) cones using a polymerase chain reaction (PCR) and to evaluate the
      sterilization effect of 5.25% sodium hypochlorite (NaOCl), 2% chlorhexidine
      (CHX), and ChloraPrep on these bacteria. Alterations of the surface texture and
      physical properties of GP cone after chemical sterilization were compared. A
      total of 150 GP cones were randomly selected in endodontic clinics, and a PCR
      assay was performed to identify the contaminating microorganisms. After
      inoculation with the same microorganisms followed by drying for 1 day, the GP
      cones were immersed in the three chemical disinfectants. The sterilization
      effects were assessed by measuring the turbidity and through subculturing. The
      changes in surface texture were observed by scanning electron microscopy, and
      Instron 5500 (Instron Corp, Canton, MA) was used to measure the tensile strength
      and elongation rate of the GP cones after chemical sterilization. Statistical
      analysis was performed. Results indicate that 19.4% of GP cones from the clinic
      were contaminated, and all the species belonged to the genus Staphylococcus.
      Three chemical disinfectants were all effective in the rapid disinfection of GP
      cones against Staphylococcus spp, and 1-minute immersion of the GP cones was
      adequate for disinfection. Microphotographs of the NaOCl-soaked cone showed a
      cluster of cuboidal crystals. The tensile strength between the NaOCl- and CHX
      soaked groups was significantly different (p<0.05), but there was no significant
      difference between the NaOCl- and ChloraPrep-soaked groups (p>0.05). All
      disinfectants significantly increased the elongation rate of the GP cones
      compared with fresh GP cones (p<0.05), especially in the ChloraPrep (Medi-flex,
      Leawood, KS). These results show that the three chemical disinfectants are
      effective agents for the rapid sterilization of GP cones. However, further
      research will be needed to determine the clinical relevance of the changes in
      physical properties.

PMID- 17437881
TI  - Advanced noninvasive light-activated disinfection: assessment of cytotoxicity on
      fibroblast versus antimicrobial activity against Enterococcus faecalis.
AB  - Recent interest in light-activated disinfection demands insight on the
      selectivity towards bacterial cells compared with mammalian cells. This study was
      aimed to evaluate the cytotoxicity and selectivity of an advanced noninvasive
      light-activated disinfection (ANILAD) developed in our laboratory. The extent of
      cytotoxic effect of methylene blue activated by visible light of wavelength 664
      nm was tested and compared with sodium hypochlorite (NaOCl) under in vitro and ex
      vivo conditions on fibroblast L929 cells. Simultaneous evaluation of cytotoxicity
      and antibacterial effect was also conducted to study the specificity of light
      activated therapy (LAT) toward prokaryotic cells (Enterococcus faecalis). The
      cytotoxicity was evaluated by 3-(4, 5-dimethylthiazol-2- yl)-2, 5
      diphenyltetrazolium bromide assay and trypan blue viability test, whereas colony
      forming units were determined to evaluate bacterial viability. Data from both in
      vitro and ex vivo experiments showed that cytotoxicity was significantly less in
      LAT compared with NaOCl (p<0.001). E faecalis cells were killed at a faster rate
      than fibroblasts. An irradiation dose producing 97.7% bacterial killing showed
      only 30% fibroblast dysfunction. This study indicated that ANILAD produced an
      insignificant effect on mammalian cells.

PMID- 17437882
TI  - Influence of the endodontic treatment on mechanical properties of root dentin.
AB  - This study evaluated the effect of endodontic treatment and storage time on the
      flexural and ultimate tensile strength of root dentin. Eighty bovine teeth were
      divided into endodontically treated (ET) and endodontically untreated (NT) teeth.
      The ET canals were instrumented and irrigated with sodium hypochlorite 1.0%.
      Roots were filled with gutta-percha and zinc-oxide/eugenol cement by the lateral
      condensation technique. Tests were performed as follows: t1, immediately; t2, 7
      days; t3, 15 days; and t4, 30 days after extraction for NT groups or after
      extraction and endodontic treatment for ET groups (n= 0). Roots were axially cut
      into two halves, one half was used to obtain bars for performing the four-bending
      flexural test and the other half to obtain slices that were trimmed resulting in
      hourglass-shaped specimens for microtensile testing. Samples were submitted to
      the tests, and the data were statistically analyzed. Results indicated that
      endodontic treatment potentiated by time elapsed after endodontic treatment can
      affect the physical properties of dentin.

PMID- 17437883
TI  - Micromorphology of enamel surface after vital tooth bleaching.
AB  - The aim of the present study was to assess microroughness changes of enamel
      surfaces after bleaching procedures with 10% and 16% concentrations of carbamide
      peroxide by confocal laser scanning microscopy. Twenty caries-free incisors,
      extracted for periodontitis reasons, were sectioned into two halves of
      experimental and control specimens. The teeth were divided into two groups, and
      the experimental specimens were exposed to either 10% or 16% carbamide peroxide
      for 4 hours per 7 days. Measurements were made at three randomly selected 140 x
      100 microm areas of 10 experimental and control specimens per group at the same
      crown level. Microroughness was measured in "total roughness" (Rt) and "average
      roughness" (Ra) descriptor values. The statistical analysis showed significantly
      higher microroughness according to Rt values and Ra values for both groups of
      carbamide peroxide exposed enamel surfaces.

PMID- 17437884
TI  - Comparison of the EndoVac system to needle irrigation of root canals.
AB  - Past studies have shown that current irrigation methods are effective at cleaning
      root canals coronally but less effective apically. To be effective, endodontic
      irrigants should ideally be delivered near working length. The purpose of this
      study was to compare the efficacy of the EndoVac irrigation system and needle
      irrigation to debride root canals at 1 and 3 mm from working length. One tooth of
      each matched pair was instrumented and irrigated by using the EndoVac, which uses
      negative pressure to deliver irrigating solutions to working length. The other
      tooth of the matched pair was instrumented and irrigated with a 30-gauge ProRinse
      irrigating needle. All teeth were irrigated with sodium hypochlorite (NaOCl) and
      ethylenediaminetetraacetic acid (EDTA) for a predetermined amount of time, and
      total volume of irrigant used was recorded. After instrumentation and irrigation,
      the teeth were fixed, decalcified, and sectioned at 1 mm and 3 mm from working
      length. Serial sections were made and digitally photographed. The amount of
      remaining debris was determined as a percentage of the area of the canal lumen.
      Remaining debris and total irrigant were analyzed by using the Wilcoxon signed
      rank test at the 5% confidence level. At the 1-mm level, significantly less
      debris was found in the EndoVac group (p=0.0347). At the 3-mm level, there was no
      significant difference between groups. Significantly more irrigant was delivered
      with the EndoVac (p<0001). This study showed significantly better debridement at
      1 mm from working length by using the EndoVac compared with needle irrigation.

PMID- 17437885
TI  - An FTIR study of the setting reaction of various endodontic sealers.
AB  - The aim of the present study was to investigate the correlation between setting
      time and setting conversion in endodontic sealers. The sealers tested were Roth's
      811, Endion, Sealapex, and AH-26 Silverfree. The setting time was recorded
      according to International Standardization Organization 6876 specification,
      whereas the setting conversion was monitored by micro-multiple internal
      reflection Fourier transform infrared spectroscopy immediately after mixing,
      before the setting time, at the setting time, and after the setting time. In
      Roth's 811, which showed the longest setting time, all free eugenol was consumed
      at the setting time. The setting conversion of Endion, Sealapex, and AH-26
      Silverfree continued after the setting time. No correlation was found between
      setting time and setting conversion because of the different setting mechanisms
      involved in the materials tested.

PMID- 17437886
TI  - Primer on the human genome.
AB  - The study of the expression patterns of many genes, or even the entire genome, is
      now routinely possible. Such powerful tools have enabled hypothesis-generating
      research at a scale never before possible. Moreover, spatially or temporally
      linked gene and protein expression, implying co-regulation and functional
      relatedness, has led to the identification of particular clusters of genes
      important for fundamental biologic processes, such as development and cancer. Not
      only is this expected to yield further mechanistic insights into disease
      processes, but perhaps most exciting, it will likely establish the foundation of
      predictive medicine, in which understanding of individual genomic signatures
      leads to the use of appropriately targeted therapy. LEARNING OBJECTIVE: At the
      conclusion of this learning activity, participants should be able to understand
      the fundamental tenets of molecular biology as they relate to the field of
      genomics.

PMID- 17437887
TI  - Nail matrix biopsy of longitudinal melanonychia: diagnostic algorithm including
      the matrix shave biopsy.
AB  - Longitudinal melanonychia (LM) may represent nail matrix melanocyte activation
      (defined as a normal number of melanocytes with increased production of melanin),
      benign hyperplasia, or melanoma, in addition to multiple nonmelanocyte
      pathologies, including hemorrhage and infection. This article details an
      algorithmic approach to LM, including a careful history and physical examination,
      dermoscopy, and ability to sample the matrix using 3 biopsy techniques, a 3-mm
      punch excision, a lateral longitudinal excision, and a matrix shave biopsy.
      Facility with all 3 techniques will allow the physician to procure appropriate
      nail matrix specimens for diagnosis.

PMID- 17437888
TI  - Basal cell carcinoma of the nail unit.
AB  - We report a case of a 70-year-old white male with a basal cell carcinoma of the
      left thumb nail unit. Excision of the tumor via Mohs micrographic surgery was
      completed in 2 stages. The defect was repaired with a full thickness skin graft.
      Five months later the nail unit healed without complications. Prior to this
      report, 21 cases of basal cell carcinoma have been reported in the world
      literature. This case, as well as the prior reports, are reviewed with a focus on
      time to diagnosis, location, excisional technique, and method of repair.

PMID- 17437889
TI  - Cell cycle and apoptosis regulators in Spitz nevi: comparison with melanomas and
      common nevi.
AB  - BACKGROUND: Deregulated cell cycle control is one of the hallmarks of tumor
      development. The expression of different cell cycle regulators has been used in
      various neoplasms as an adjunct to diagnosis. OBJECTIVE: We sough to determine
      the expression of cell cycle and apoptosis regulators in Spitz nevi and to
      appraise its value as a diagnostic adjunct in the differential diagnosis from
      melanomas and common nevi. METHODS: Ki-67, p-27, p-16, p-53, p-21, Rb, cyclin D1,
      cyclin A, cyclin B1, bcl-2, and bax expression was assessed by
      immunohistochemistry in 10 Spitz nevi and was compared with 16 melanomas and 20
      common nevi immunohistochemical expression. RESULTS: P-27 (60% +/- 20.13), p-16
      (62.00% +/- 10.85), and bcl-2 (46.00% +/- 42.47) were highly expressed in Spitz
      nevi, whereas Ki-67 (2.80% +/- 2.55), Rb (3.75% +/- 4.55), p-53 (2.30% +/- 0.10),
      cyclin A (0.70% +/- 1.56), B1 (0.20% +/- 0.34), and bax (2.65% +/- 6.37)
      demonstrated a limited expression. Cyclin D1 (8.60% +/- 7.30) and p-21 (6.40% +/-
      5.37) showed a moderate expression. The expression of bax (P = .001), Ki-67 (P <
      .0001), Rb (P < .0001), p-16 (P < .0001), cyclin A (P < .0001), and cyclin B1 (P
      < .0001) was significantly higher in melanomas in comparison with Spitz nevi,
      whereas p-27 expression was significantly higher in Spitz nevi (P < .0001). A
      trend for significant difference in favor of melanomas was also observed for p-53
      (P = .002). On the other hand, no difference was detected for bcl-2 (P = .275), p
      21 (P = .055), or cyclin D1 (P = .077). Spitz nevi demonstrated a trend for a
      higher expression for p-21 (P = .008) and cyclin D1 (P = .006), whereas they
      exhibited lower p-16 (P = .004) in comparison with common nevi. LIMITATIONS: The
      number of Spitz nevi was relatively small. CONCLUSION: Spitz nevi differ from
      melanomas in their immunohistochemical pattern of expression of cell cycle and
      apoptosis regulators and more closely resemble common benign nevi.

PMID- 17437890
TI  - Age distribution of biopsied junctional nevi.
AB  - BACKGROUND: Junctional nevi are traditionally associated with children and
      younger patients. We noticed that these lesions are also often found in elderly
      patients. OBJECTIVE: We sought to determine if junctional nevi are found in all
      age groups. METHODS: All biopsy reports for junctional nevi for the year 2001 at
      the Penn State Milton S. Hershey Medical Center were reviewed. Age of patients
      and locations for these nevi were noted and the results analyzed. RESULTS: The
      age distribution of junctional nevi shows that these lesions occur with similar
      frequency in the young and in the elderly. Lesions were more frequent in non-sun
      exposed skin. LIMITATIONS: The age distribution between biopsied nevi and nevi
      not biopsied may be different. Sampling error may also lead to mis-classification
      of nevi. CONCLUSION: Junctional nevi are common in all age groups.

PMID- 17437891
TI  - Antipsoriatic biologic agents for the treatment of atopic dermatitis.
AB  - Dialogues in Dermatology, a monthly audio program from the American Academy of
      Dermatology, contains discussions between dermatologists on timely topics.
      Commentaries from Dialogues Editor-in-Chief Warren R. Heymann, MD, are provided
      after each discussion as a topic summary and are provided here as a special
      service to readers of the Journal of the American Academy of Dermatology.

PMID- 17437892
TI  - "Anisotrichosis": a novel term to describe pattern alopecia.

PMID- 17437894
TI  - Melanocytic nevus with focal atypical epithelioid components (clonal nevus) is a
      combined nevus.

PMID- 17437895
TI  - Keratin intermediate filament retraction is linked to plakoglobin-dependent
      signaling in pemphigus vulgaris.

PMID- 17437897
TI  - Patient adherence with treatment.

PMID- 17437898
TI  - Is postsurgical sternal erythema synonymous with reticular telangiectatic
      erythema?

PMID- 17437899
TI  - Reconsidering liver biopsies during methotrexate therapy.

PMID- 17437900
TI  - Acne, breast cancer, and androgens.

PMID- 17437901
TI  - A satellite symposium of the 1st European Congress of Immunology Paris, France,
      September 2006, Aging Research in Immunology: the genomic facet in Paris.

PMID- 17437903
TI  - Multimodality comparison of neuroimaging in pediatric traumatic brain injury.
AB  - Traumatic brain injury is a common cause of death and disability in children;
      early neuroimaging has assumed an increasingly important role in evaluating the
      extent and severity of injury. Several imaging methods were assessed in a study
      of 40 children with traumatic brain injury: computed tomography (CT), T(2)
      weighted magnetic resonance imaging (MRI), fluid-attenuated inversion recovery
      (FLAIR) MRI, and susceptibility-weighted imaging (SWI) MRI to determine which
      were most valuable in predicting 6-12 month outcomes as classified by the
      Pediatric Cerebral Performance Category Scale score. Patients were subdivided
      into three groups: (1) normal, (2) mild disability, and (3) moderate/severe
      disability/persistent vegetative state. T(2), FLAIR, and SWI showed no
      significant difference in lesion volume between normal and mild outcome groups,
      but did indicate significant differences between normal and poor and between mild
      and poor outcome groups. Computed tomography revealed no significant differences
      in lesion volume between any groups. The findings suggest that T(2), FLAIR, and
      SWI MRI sequences provide a more accurate assessment of injury severity and
      detection of outcome-influencing lesions than does CT in pediatric traumatic
      brain injury patients. Although CT was inconsistent at lesion detection/outcome
      prediction, it remains an essential part of the acute traumatic brain injury work
      up to assess the need for neurosurgic intervention.

PMID- 17437904
TI  - Levetiracetam monotherapy in children with epilepsy.
AB  - Although levetiracetam has shown efficacy in children with epilepsy, when used as
      adjunctive therapy, limited data are available regarding its use as monotherapy.
      The objective of this study is to evaluate the efficacy and tolerability of
      levetiracetam monotherapy in a cohort of pediatric patients with epilepsy. A
      retrospective analysis of pediatric epilepsy patients receiving levetiracetam at
      a single institution was performed over a 3-year period. Eighty-one patients were
      identified, 18 of whom received levetiracetam as monotherapy (mean age, 9.6
      years). Epilepsy types were partial in 14 and generalized in 4. Conversion to
      levetiracetam monotherapy occurred in 16 patients due to lack of efficacy or
      adverse events, and 2 patients were initially started on monotherapy. Dose range
      of levetiracetam was 14-60 mg/kg, and duration of therapy ranged from 2-24
      months. Eleven patients became seizure free on levetiracetam, one had at least
      50% reduction in seizures, and six others had no change in seizure frequency.
      Adverse events included worsening of behavior, irritability, and possible
      cognitive changes, seen in 4 patients. Levetiracetam was discontinued in seven
      patients overall. Levetiracetam monotherapy appeared to be effective and well
      tolerated in this group of children with epilepsy and warrants further
      investigation in a well-controlled, prospective study.

PMID- 17437902
TI  - Ischemic spinal cord infarction in children without vertebral fracture.
AB  - Spinal cord infarction in children is a rare condition that is becoming more
      widely recognized. There are few reports in the pediatric literature
      characterizing etiology, diagnosis, treatment, and prognosis. The risk factors
      for pediatric ischemic spinal cord infarction include obstruction of blood flow
      associated with cardiovascular compromise or malformation, iatrogenic or
      traumatic vascular injury, cerebellar herniation, thrombotic or embolic disease,
      infection, and vasculitis. In many children, the cause of spinal cord ischemia in
      the absence of vertebral fracture is unknown. Imaging diagnosis of spinal cord
      ischemia is often difficult, due to the small transverse area of the cord,
      cerebrospinal fluid artifact, and inadequate resolution of magnetic resonance
      imaging. Physical therapy is the most important treatment option. The prognosis
      is dependent on the level of spinal cord damage, early identification and
      reversal of ischemia, and follow-up with intensive physical therapy and medical
      support. In addition to summarizing the literature regarding spinal cord
      infarction in children without vertebral fracture, this review article adds two
      cases to the literature that highlight the difficulties and controversies in the
      management of this condition.

PMID- 17437905
TI  - Semiological seizure classification: before and after video-EEG monitoring of
      seizures.
AB  - The study objective was to assess the applicability and reliability of the
      semiological seizure classification in children with epilepsy in outpatient
      clinics. Ninety patients (age range, 2-16 years) who experienced clinical
      seizures during prolonged video-electroencephalogram (EEG) monitoring were
      evaluated. Semiological seizure classification was performed, first based on
      history obtained from parents of the patient during outpatient follow-up visits
      and then based on video EEG-monitoring. Kappa statistics (kappa) were used to
      evaluate the consistency of the two rounds of semiological seizure
      classification. Classification based on history yielded the following
      distribution: simple motor seizures (66.3%), aura (28%), complex motor seizures
      (15.8%), special seizures (15.8%), dialeptic seizures (9.3%), and autonomic
      seizures (3.7%). Classification based on video EEG-monitoring yielded a different
      distribution: simple motor seizures (55.7%), complex motor seizures (26.9%),
      automotor seizures (26.9%), aura (23%), dialeptic seizures (22.1%), special
      seizures (9.6%), and autonomic seizures (1.9%). Negative myoclonic seizures
      (kappa = 1, P = 0.000) and hypermotor seizures (kappa = 0.85, P = 0.000) had
      excellent consistency; somatosensory aura (kappa = 0.26, P = 0.012) and automotor
      seizures (kappa = 0.28, P = 0.004) had the lowest consistency. The families or
      doctors often defined simple motor seizures (decrease of 10.6% from before to
      after monitoring, kappa = 0.44); the proportion of complex motor seizures changed
      rather from before to after monitoring (11.1%, kappa = 0.33). Generally, parents
      can describe seizures quite well. We suggest that semiological seizure
      classification is a reliable method applicable for everyday use during outpatient
      visits, especially if seizure semiology is evaluated individually for each
      component or if the semiological seizure classification is modified or refined
      for some seizure components (tonic, clonic, versive, conscious, automotor
      seizures).

PMID- 17437906
TI  - Focal cerebral mantle disruption in fetal hydrocephalus.
AB  - A variety of developmental brain anomalies have been described in individuals
      with fetal hydrocephalus, regardless of etiology. Examples include callosal
      dysgenesis, periventricular gray matter heterotopia, hippocampal and white matter
      hypoplasia, and cortical polygyration. The present report draws attention to
      another anomaly not reported in previous case series of fetal hydrocephalus:
      focal cerebral mantle disruption. Neonatal imaging findings (where available) and
      post-shunt, stable-state magnetic resonance imaging, or pathological findings
      were reviewed in 77 subjects with fetal hydrocephalus (55 myelomeningocele, 16
      sporadic aqueductal stenosis, 6 miscellaneous). Of these, 12 subjects (15.6%)
      demonstrated a combination of absence of the septum pellucidum and severe
      thinning or absence of the posteromesial cerebral mantle. On axial sequences,
      this combination created the illusion of a common ventricle, as in lobar
      holoprosencephaly. All 12 subjects had massive hydrocephalus at birth,
      accompanied in 7 by posteromesial ventricular diverticula. Two subjects, and one
      other subject with distinct lateral ventricles, demonstrated unilateral or
      bilateral mantle clefts suggestive of schizencephaly. Close radiological (n = 2)
      or pathological (n = 1) inspection showed that the clefts were only partially
      lined with gray matter and contained a transverse gliotic membrane. These
      findings are consistent with the hypothesis that massive early fetal
      hydrocephalus may completely disrupt cerebral mantle formation, particularly in
      the posteromesial hemispheres.

PMID- 17437907
TI  - Ischemic stroke in children with critical illness: a poor prognostic sign.
AB  - A consecutive case series of 55 children (0-17 years old) with arterial ischemic
      stroke is reported. Twenty of these children were critically ill at the time
      their stroke occurred. Mortality among these 20 children was 40%, compared with
      3% in non-critically ill children with arterial ischemic stroke; overall
      mortality in this case series was 16%. Mortality resulted primarily from the
      underlying illness. Prognosis after stroke is markedly worsened in children with
      premorbid critical illness.

PMID- 17437908
TI  - Childhood-onset idiopathic intracranial hypertension: relation of sex and
      obesity.
AB  - The purpose of the present study was to perform a meta-analysis of all children
      with idiopathic intracranial hypertension reported since 1997 combined with our
      experience in order to investigate sex distribution and frequency of obesity
      among young children up 11 years of age vs adolescents at age 12-17 years.
      Overall, 244 children diagnosed with idiopathic intracranial hypertension were
      found suitable for the proposed meta-analysis: 132 (54%) were younger than 11
      years of age; 72 (55%) were male and 60 (44%) were female. In contrast, of 112
      older children (age 12-17 years), 79 (70%) were female. The association between
      age and obesity could be analyzed in 147 patients: only 19 (26%) out of 74
      younger children up to age 11 years were reportedly obese, whereas 47 (64%) out
      of 73 older children were found obese. Differences in age at presentation, sex,
      and obesity were statistically significant (P < 0.01). Thus, a wide-scale meta
      analysis of childhood-onset idiopathic intracranial hypertension revealed that
      the female/male ratio in children younger than age 11 years seems to be fairly
      equal, with a relatively low rate of obesity, contrasting to a majority of
      females in the group of adolescents at high risk to become obese.

PMID- 17437909
TI  - Peripheral neuropathy in cardiofaciocutaneous syndrome.
AB  - A young adult male with cardiofaciocutaneous syndrome developed gait
      deterioration in childhood, with later evolution of distal wasting. His physical
      examination revealed intention tremor, distal weakness of the upper limbs with
      atrophy of the thenar, hypothenar, and interossei muscles, a wide-based gait, and
      large-fiber sensory loss in all limbs. Neuroimaging revealed stable mild chronic
      communicating hydrocephalus. Nerve conduction studies and electromyography
      demonstrated a moderately severe axonal neuropathy. The present case is, to our
      knowledge, the first reported case of peripheral neuropathy in association with
      cardiofaciocutaneous syndrome. The latter is a rare disorder, with significant
      comorbidities, in which a peripheral neuropathy may be under-recognized as a late
      cause of functional deterioration.

PMID- 17437910
TI  - Childhood status epilepticus and excitotoxic neuronal injury.
AB  - This report describes the case of an 11-year-old girl with a prior history of
      epilepsy and multiple episodes of status epilepticus who presented with
      generalized convulsive status epilepticus and left hemiclonic seizures. Magnetic
      resonance imaging, including diffusion-weighted sequences and spectroscopy, and
      neuropathology at autopsy were consistent with excitotoxic neuronal injury to the
      hippocampus, cortex, thalamus, mammillary bodies, and cerebellum. Review of the
      literature revealed 11 similar cases that support the hypothesis of excitotoxic
      neuronal cell death after status epilepticus.

PMID- 17437911
TI  - Partial deletion of LIS1: a pitfall in molecular diagnosis of Miller-Dieker
      syndrome.
AB  - Miller-Dieker syndrome represents a microdeletion syndrome spanning the LIS1
      locus at 17p13.3, the deletion of which leads to lissencephaly. A fluorescence in
      situ hybridization study using an LIS1 probe is considered the standard
      laboratory diagnostic method for Miller-Dieker syndrome. This report documents a
      Miller-Dieker syndrome patient who tested normal when a commercially available
      LIS1 fluorescence in situ hybridization study probe was used but was later
      demonstrated to have a partial deletion of the LIS1 locus. The present case
      exemplifies a major shortcoming of commercially available fluorescence in situ
      hybridization studies for the diagnosis of microdeletion syndromes such as Miller
      Dieker syndrome: that is, relatively small deletion can potentially remain
      undetected.

PMID- 17437912
TI  - Two cases of fatal meningitis due to Fusobacterium necrophorum.
AB  - It is extremely important to consider Fusobacterium necrophorum as a cause of
      meningitis in children after otitis or other upper respiratory tract infections,
      because of its increasing incidence. A high index of suspicion and prompt
      microbiological identification are mandatory; as this organism is often
      penicillin-resistant, prolonged antibiotic therapy is required and invasive
      infection carries a high risk of fatal cerebral vessel thrombosis. This report
      presents two fatal cases who presented to our pediatric intensive care unit in
      December 2004.

PMID- 17437913
TI  - Neuroimage findings in 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency.
AB  - A case of 2-methyl-3-hydroxybutyryl-coenzyme A dehydrogenase deficiency, an X
      linked defect of isoleucine degradation, is reported. A 10-month-old male infant
      with developmental regression, visual impairment, movement disorder, and
      seizures, he suffered acute deterioration with multiorganic failure after a
      respiratory infection. Laboratory studies revealed hyperlactacidemia and
      increased excretion of 2-methyl-3-hydroxybutyric acid (2M3HBA) and tiglylglycine
      (TG). The diagnosis was established by molecular genetic analysis of the involved
      X-chromosome gene HADH2. The patient was hemizygous for the mutation R130C (c.
      388C>T). Magnetic resonance imaging disclosed frontotemporal atrophy and
      bilateral signal abnormalities in the putamina. The presence of basal ganglia
      abnormalities and lactic acidemia, also shared by mitochondrial disorders,
      suggests a common pathophysiologic mechanism of damage.

PMID- 17437914
TI  - Contrast-induced seizures after cardiac catheterization in a 6-year-old child.
AB  - Neurologic complications of cardiac catheterization are usually embolic events
      resulting in stroke or seizures of vascular origin. Contrast-induced seizures
      have been rarely described in children. This report presents clinical,
      neuroimaging, and follow-up data of a 6-year-old female subjected to cardiac
      catheterization for aortic coarctation who developed contrast-induced generalized
      seizures. Although rare, this condition adds to the neurologic complications of
      cardiac catheterization in children and should be considered in the differential
      diagnosis of seizures of vascular origin with obvious therapeutic and prognostic
      implications.

PMID- 17437915
TI  - Acute motor axonal neuropathy--an atypical presentation.
AB  - Guillain-Barre syndrome, an autoimmune disorder of the peripheral nervous system,
      is divided into several subtypes according to clinico-pathologic findings and
      epidemiologic characteristics. A pure motor variant without involvement of the
      sensory nerves has been reported in rare cases. This report details the clinical,
      immunologic, and serial electrophysiologic findings of two patients with an
      acute, exclusively motor, axonal neuropathy.

PMID- 17437916
TI  - Neonatal hypocalcemic seizures in siblings exposed to topiramate in utero.
AB  - We describe two siblings with neonatal hypocalcemic seizures whose mother took
      topiramate during both pregnancies. Apart from hypocalcemia, the patients had no
      identifiable etiology for their seizures. Although biochemical data suggested
      that the hypocalcemia was caused by hypoparathyroidism, no disorders typically
      associated with this condition were identified in the patients. We propose that
      topiramate exposure in utero led to hypoparathyroidism and subsequent
      hypocalcemia via effects on protein kinase A signaling, resulting in hypocalcemic
      seizures. Neonates exposed to topiramate in utero should be monitored for
      hypocalcemic seizures.

PMID- 17437917
TI  - Grandpa and I have dystrophinopathy? Approach to asymptomatic hyperCKemia.

PMID- 17437918
TI  - Congenital cytomegalovirus infection associated with corpus callosum agenesis.

PMID- 17437930
TI  - The complexities of homeopathic prescribing or how do we decide to do what we do?

PMID- 17437931
TI  - What do homeopathic dentists do?

PMID- 17437932
TI  - Outcomes from homeopathic prescribing in dental practice: a prospective, research
      targeted, pilot study.
AB  - BACKGROUND AND AIMS: A base for targeted research development in dental
      homeopathy can be founded on systematic collection and analysis of relevant data
      obtained by dentists in clinical practice. With these longer-term aims in mind,
      we conducted a pilot data collection study, in which 14 homeopathic dentists
      collected clinical and outcome data over a 6-month period in their practice
      setting. METHODS: A specifically designed Excel spreadsheet enabled recording of
      consecutive dental appointments under the following main headings: date; patient
      identity (anonymised), age and gender; dental condition/complaint treated;
      whether chronic or acute, new or follow-up case; patient-assessed outcome (7
      point Likert scale: -3 to +3) compared with first appointment; homeopathic
      medicine/s prescribed; whether any other medication/s being taken for the
      condition. Spreadsheets were submitted monthly via e-mail to the project co
      ordinator for data synthesis and analysis. RESULTS: Practitioners typically
      submitted data regularly and punctually, and most data cells were completed as
      required, enabling substantial data analysis. The mean age of patients was 46.2
      years. A total of 726 individual patient conditions were treated overall. There
      was opportunity to follow-up 496 individual cases (positive outcome in 90.1%;
      negative in 1.8%; no change in 7.9%; outcome not recorded in 0.2%). Sixty-four of
      these 496 patients reported their outcome assessment before the end of the
      homeopathic appointment. Strongly positive outcomes (scores of +2 or +3) were
      achieved most notably in the frequently treated conditions of pericoronitis,
      periodontal abscess, periodontal infection, reversible pulpitis, sensitive
      cementum, and toothache with decay. CONCLUSIONS: This multi-practitioner pilot
      study has indicated that systematic recording of practice data in dental
      homeopathy is both feasible and capable of informing future research. A refined
      version of the spreadsheet can be employed in larger-scale research-targeted data
      collection in the dental practice setting.

PMID- 17437933
TI  - Individualized homeopathic treatment of trigeminal neuralgia: an observational
      study.
AB  - OBJECTIVE: To evaluate individualized classical homeopathy in the treatment of
      idiopathic trigeminal neuralgia (ITN) METHOD: 15 patients with physician
      confirmed trigeminal neuralgia were treated with homeopathy. Patients received
      individualized homeopathic medicines as oral liquid 30C once per month and were
      followed-up at the end of first, second, third and fourth month. Visual analogue
      scale (VAS) was used for the evaluation of pain intensity and descriptive
      criteria were used for evaluation of attack frequency. RESULT: All 15 patients
      completed treatment. The results for both the reduction of pain intensity and
      attack frequency were statistically significant (P<0.001) during the four-month
      evaluation. We observed overall reductions of more than 60% in pain intensity
      using homeopathic treatment. CONCLUSION: The results suggest that homeopathic
      treatment is an effective and safe method in the treatment of ITN.

PMID- 17437934
TI  - Patients treated by homeopaths registered with the Society of Homeopaths: a pilot
      study.
AB  - BACKGROUND: There is little information on the types of symptoms for which
      patients request homeopathic treatment from Society of Homeopaths (SoH)
      homeopaths in the UK. OBJECTIVES: A preliminary study to gain information about
      characteristics of patients requesting treatment from SoH professional (non
      medically qualified) homeopaths--including symptoms and general well-being.
      RESULTS: 37 homeopaths returned data on 482 patients covering 1419 consultations
      over a 2 year period. Patients were mostly female and predominantly aged 40-59.
      CONCLUSIONS: As well as obtaining preliminary data about these patients, this
      study has also resulted in greater knowledge of audit and research methods in the
      profession. The results of this preliminary descriptive study will inform a
      future, larger prospective controlled observational study.

PMID- 17437935
TI  - Clinical management of babesiosis in dogs with homeopathic Crotalus horridus
      200C.
AB  - Homeopathic Crotalus horridus 200C was evaluated in 13 clinical cases of
      babesiosis in dogs, compared with another 20 clinical cases treated with
      diminazine. Babesiosis is an important tropical tick-borne haemoprotozoan disease
      in dogs clinically manifested by anorexia, dehydration, temperature,
      dullness/depression, diarrhoea/constipation, pale mucosa, hepatomegaly,
      vomiting/nausea, splenomegaly, distended abdomen/ascites, yellow coloured urine,
      emaciation/weight loss, and occular discharge. The diagnosis of babesiosis was
      based on cytological evidence of Babesia gibsoni in freshly prepared blood
      smears. The dogs were treated with oral C. horridus 200C, 4 pills four times
      daily for 14 days (n=13) or diminazine aceturate 5 mg/kg single intramuscularly
      dose (n=20). All the dogs were administered 5% Dextrose normal saline at 60 ml/kg
      intravenously for 4 days. Initial clinical scores were similar in both groups and
      showed similar progressive improvement with the two treatments over 14 days.
      Parasitaemia also improved in both groups, but haematological values showed no
      change. No untoward reactions were observed. It appears that C. horridus is as
      effective in causing clinical recovery in moderate cases of canine babesiosis
      caused by Babesia gibsoni as the standard drug diminazine. Large scale randomized
      trials are indicated for more conclusive results.

PMID- 17437936
TI  - In vivo study of the anti-inflammatory effect of Rhus toxicodendron.
AB  - BACKGROUND: Homeopathic Rhus toxicodendron (Rhus tox) is used in various
      inflammatory conditions. We screened its effect compared to succussed ethanol
      controls and appropriate active controls. METHOD: We initially experimented with
      Rhus tox 6, 12, 30 and 200 cH, using carrageenan-induced paw oedema in rats. The
      6 cH dilution appeared most effective and was used in subsequent assays. We used
      pre-treatment and single treatment regimes in Wistar rats, and mice. RESULTS: We
      found significant reductions compared to control in carrageenan-induced paw
      oedema, vascular permeability, writhing induced by intraperitoneal acetic acid
      and stress induced gastric lesions. CONCLUSIONS: Rhus tox in homeopathic dilution
      appears to interfere with inflammatory processes involving histamine,
      prostaglandins and other inflammatory mediators.

PMID- 17437937
TI  - The vital sensation of the minerals: reducing uncertainty in homeopathic
      prescribing.
AB  - We illustrate the 'vital sensation' of mineral-based homeopathic medicines as
      revealed by an interview style based on a synthesis of the Bombay method and
      Scholten's, understanding derived from the periodic table. The 'Bombay method',
      described by Rajan Sankaran, builds on homeopathic teaching giving a structure to
      guide the gathering and synthesising homeopathic data. The concept of 'levels'
      gives a route to the deepest reflection of the vital disturbance, the vital
      sensation. Moving through the levels of fact, symptom, emotion, delusion and
      finally vital sensation provides valuable prescribing information. These aspects
      are discussed in conjunction with the kingdoms: plant, mineral and animal,
      focusing on the mineral kingdom. By synthesizing information relating to the
      concepts of vital sensation and kingdom we can reduce uncertainly in homeopathic
      prescribing.

PMID- 17437938
TI  - Can homeopathy learn something from psychoanalysis?
AB  - This paper attempts to demonstrate how some insights from psychoanalysis can be
      useful in homeopathic treatment. I discuss three concepts: I illustrate these
      concepts with the case of a 23-year-old woman with chronic fatigue syndrome. (1)
      The working alliance: comparing medical alliance with a psychodynamic alliance.
      (2) The dream-function: serious somatic disorders can be the result of a blocked
      dream function, the restoration of the capacity to dream may lead to the
      disappearance of these disorders, homeopathy can help in this process. (3) The
      transgenerational influence: some traumatic, concealed events from the lives of
      ancestors can influence their descendants.

PMID- 17437939
TI  - Hypothesis: do homeopathic medicines exert their action in humans and animals via
      the vomeronasal system?
AB  - There is significant debate on the nature of the active therapeutic ingredient in
      homeopathic medicines and whether the effect of homeopathic medicines is exerted
      locally. This paper accepts that there is an active therapeutic ingredient in
      homeopathic medicines that acts pharmacologically in the body and proposes a
      possible receptor site. The vomeronasal organ (Jacobson's organ) is the receptor
      site for the detection of non-odorant molecules, eg pheromones, in reptiles,
      amphibians and mammals. The organ forms the main part of a chemoreceptor system
      known as the vomeronasal system. This paper proposes that it is this system that
      constitutes the receptor for homeopathic medicines in both animal and human
      subjects.

PMID- 17437940
TI  - Bayesian homeopathy: talking normal again.
AB  - Homeopathy has a communication problem: important homeopathic concepts are not
      understood by conventional colleagues. Homeopathic terminology seems to be
      comprehensible only after practical experience of homeopathy. The main problem
      lies in different handling of diagnosis. In conventional medicine diagnosis is
      the starting point for randomised controlled trials to determine the effect of
      treatment. In homeopathy diagnosis is combined with other symptoms and personal
      traits of the patient to guide treatment and predict response. Broadening our
      scope to include diagnostic as well as treatment research opens the possibility
      of multi factorial reasoning. Adopting Bayesian methodology opens the possibility
      of investigating homeopathy in everyday practice and of describing some aspects
      of homeopathy in conventional terms.

PMID- 17437941
TI  - 20 years ago: The British Homoeopathic Journal, April 1987.

PMID- 17437942
TI  - Ultradilute hybrid DNA dot-blot phenomenon.

PMID- 17437943
TI  - Bronchodilators, fatal asthma, rebound effect and similitude.

PMID- 17437944
TI  - Proceedings of the 2nd TMS Symposium on Biological Materials Science, March 12
      16, 2006, San Antonio, Texas, USA.

PMID- 17437948
TI  - [Some neurological and psychiatric complications of the disorders of the
      hypothalamo-hypophyseal system].
AB  - Connection between the central nervous system and the endocrine system is
      extremely complex. The hypothalamus serves as a crucial centre for the
      integration and coordination of autonomic functions by neuronal and hormonal
      pathways. It plays a central role in the homeostatic regulation of internal
      physiological conditions. It controls growth and reproduction, stress reactions,
      and determines rhythmicity, periodicity and timing of physiological processes.
      Beside its well-known functions, antidiuretic hormone has a role in social
      behavior as it enhances aggression via vasopressin receptor 1A. Oxitocin is
      affected in the formation of maternal behavior, and in other social interactions,
      like the pair bounding, as well as in analgesia and pain modulation. The
      corticotrop-releasing hormone acts as a neurotransmitter, it has a special role
      in stress-behavior, anxiety, and depression, and it blocks deep sleeping. Among
      the neurotransmitters and neuropeptids of the hypothalamus, serotonin,
      norepinephrine, GABA, cholecystokinin, neuropeptide-Y, Agouti-related protein,
      alpha-MSH and ghrelin have essential importance in the eating disorders. The
      levels of leptin and galanin determine whether formation of anabolic or catabolic
      neurotransmitters should take place. In the thermoregulation the central
      thermoreceptors play role, and suprachiasmatic nucleus is responsible for
      circadian rhythm, through "timing genes". The diseases of the hypothalamus cause
      most frequently bulimia or anorexia, hypersomnia, impotency, and attacks of
      anxiety. The most common expansive process of the hypothalamus is
      craniopharyngioma. The lack or diminution of vasopressin causes diabetes
      insipidus, while inappropriate antidiuretic hormone secretion induces Schwartz
      Barter syndrome. Frohlich-, Kleine-Levin- or Prader-Willi syndromes have
      characteristic neuropsychiatric features. The main psychiatric symptom of
      hypopituitarism is a combination of dementia and delirium. The most
      characteristic neurological sign of pituitary adenoma is the visual field defect.
      Carpal tunnel syndrome, obstructive sleeping apnoe and headache are typical
      neurological features in somatotrop adenomas.

PMID- 17437949
TI  - [The effects of seasonal variations and weather conditions on the occurrence of
      heart attacks in Hungary between 2000-2004].
AB  - INTRODUCTION: The onset of acute myocardial infarct shows circadian and seasonal
      variations, that are influenced by sex, age and the changes of weather conditions
      as well. AIM: The purpose of our present study is to investigate whether a
      seasonal variation can be found in the onset of myocardial infarctions during the
      period under investigation, and whether certain meteorological factors (air
      temperature, atmospheric pressure, front movements) influence the incidence of
      myocardial infarction. METHODS: Retrospective analysis has been carried out on
      patients admitted because of acute myocardial infarct in Hungary between 2000 and
      2004 ( n=81.956). Data have been taken from the database of the National Health
      Insurance Fund Administration based on the International Classification of
      Diseases (ICD). Weather related data were provided by the National Meteorology
      Service. RESULTS: Regarding seasonal distribution the peak incidence period of
      acute myocardial infarct was spring, whereas the lowest number of events was
      observed during the summer months. There was a marked difference in the number of
      events per season ( p<0.001). A medium level negative correlation was found
      between the monthly average temperature and the occurrence of heart attack ( r=
      0.404) during the period examined. A positive correlation was shown between front
      movements and the of number of events per season ( r=0.053). CONCLUSION: Our
      findings show that certain meteorological factors may be related to the onset of
      acute myocardial infarct, however, a number of other factors may also play an
      important role.

PMID- 17437950
TI  - [Complex analysis of prognostic factors in chronic lymphocytic leukemia].
AB  - INTRODUCTION: Many new prognostic factors established in recent years in chronic
      lymphocytic leukemia. May help predicting survival. AIMS: The goal of the present
      study was to determine the frequency and the correlation of these novel
      prognostic factors in samples of 419 leukemia patients. METHODS: The mutation
      status of the IgH gene was evaluated in 160 cases. RESULTS: In 62% of cases, non
      mutated IgH gene was found, the heavy chain family usage was different in mutated
      and non-mutated cases. The CD38 expression demonstrated 78% concordance with the
      mutation status, the ZAP-70 expression failed to show any correlation.
      Cytogenetic abnormalities were seen in 76% of cases, the most frequent were
      del(13q) (57%), trisomy 12 (15%), del(11q) (12%) and del(17p) (6%). 95% of cases
      with del(11q) harbored non-mutated, 74% of cases with del(13q) as the sole
      anomaly demonstrated mutated IgH genes. CONCLUSIONS: The parameters analysed are
      not independent of each other, utilization of them in the clinical routine needs
      careful planning.

PMID- 17437951
TI  - [The pathophysiology, clinical signs and therapy of urate nephropathy].
AB  - Tumor lysis syndrome is an oncologic emergency that is characterized by severe
      electrolyte abnormalities. The syndrome occurs in patients with
      lymphoproliferative malignancies, most often after chemotherapy, but also
      spontaneously. The pathophysiology involves tumor cell lysis resulting in the
      release of potassium, phosphate and uric acid. The deposition of uric acid and
      calcium phosphate crystals in the renal tubules may lead to acute renal failure.
      The treatment consists in hydration, correction of the acidosis and hyperkalemia,
      use of allopurinol and recombinant urate oxidase (rasburicase) for preventing
      urate nephropathy and haemodialysis. The authors report a case of a patient with
      acute myeloid leukemia, who developed severe tumor lysis syndrome after
      chemotherapy.

PMID- 17437952
TI  - [Intravascular lymphomatosis: diagnostic problems of a rare disease].
AB  - Intravascular lymphomatosis is a rare systemic disease characterized by
      proliferation of malignant B or rarely T lymphocytes. Skin and the brain are
      predominantly affected. We describe a patient presenting with focal neurological
      signs and progressive dementia. Cerebral neuroimaging findings were nonspecific.
      Postmortem examination revealed intravascular proliferation of atypical
      mononuclear cells in the lumens of small vessels in all organs. The authors
      conclude that diagnosis requires a high index of suspicion and pathological
      examination of the affected organs, but is rarely made ante mortem.

PMID- 17437953
TI  - [Markusovszky's cult in the county Vas and in the hospital of Szombathely].

PMID- 17437956
TI  - Lung cancer mortality at a UK tin smelter.
AB  - BACKGROUND: An earlier study of mortality among male former employees at a tin
      smelter in Humberside, UK, had identified excess mortality from lung cancer,
      which appeared to be associated with occupational exposure. AIMS: The aim of the
      present study was to investigate the relationship between lung cancer mortality
      and quantitative measures of exposure. METHODS: Using available records of
      occupational hygiene measurements, we established exposure matrices for arsenic,
      cadmium, lead, antimony and polonium-210 ((210)Po), covering the main process
      areas of the smelter. We established work histories from personnel record cards
      for the previously defined cohort of 1462 male employees. Three different methods
      of extrapolation were used to assess exposures prior to 1972, when no measurement
      results were available. Lung cancer mortality was examined in relation to
      cumulative inhalation exposure by Poisson regression analysis. RESULTS: No
      significant associations could be found between lung cancer mortality and simple
      cumulative exposure to any of the substances studied. When cumulative exposures
      were weighted according to time since exposure and attained age, significant
      associations were found between lung cancer mortality and exposures to arsenic,
      lead and antimony. CONCLUSIONS: The excess of lung cancer mortality in the cohort
      can most plausibly be explained if arsenic is the principal occupational
      carcinogen (for which the excess relative risk diminishes with time since
      exposure and attained age) and if there is a contribution to excess mortality
      from an enhanced prevalence of smoking within the cohort. The implications of the
      dose-response for arsenic exposure for risk estimation merit further
      consideration.

PMID- 17437957
TI  - Deaf college students' perceptions of their social-emotional adjustment.
AB  - This study examined differences between deaf and hearing students' perceptions of
      their social emotional adjustment as they transition to college. The 16PF
      Adolescent Personality Questionnaire Life Difficulties Scale was completed by 205
      deaf students and 185 hearing students. A multivariate analyses of variance and
      subsequent univariate tests found that deaf students rated themselves as
      experiencing significantly higher home life difficulties than hearing students,
      and deaf students rated themselves as having fewer coping difficulties than
      hearing students. Results also revealed a hearing status by gender interaction
      with deaf females rating themselves significantly higher on worry than deaf
      males, hearing females, and hearing males. An exploratory factor analysis of the
      Life Difficulties subscales yielded three factors of life difficulties for deaf
      college students but only two factors for hearing college students. These
      findings suggest that there are differences between deaf and hearing students who
      are transitioning to college with regards to their social-emotional adjustment.

PMID- 17437958
TI  - Elevated basal slippage mutation rates among the Canidae.
AB  - The remarkable responsiveness of dog morphology to selection is a testament to
      the mutability of mammals. The genetic sources of this morphological variation
      are largely unknown, but some portion is due to tandem repeat length variation in
      genes involved in development. Previous analysis of tandem repeats in coding
      regions of developmental genes revealed fewer interruptions in repeat sequences
      in dogs than in the orthologous repeats in humans, as well as higher levels of
      polymorphism, but the fragmentary nature of the available dog genome sequence
      thwarted attempts to distinguish between locus-specific and genome-wide origins
      of this disparity. Using whole-genome analyses of the human and recently
      completed dog genomes, we show that dogs possess a genome-wide increase in the
      basal germ-line slippage mutation rate. Building on the approach that gave rise
      to the initial observation in dogs, we sequenced 55 coding repeat regions in 42
      species representing 10 major carnivore clades and found that a genome-wide
      elevated slippage mutation rate is a derived character shared by diverse wild
      canids, distinguishing them from other Carnivora. A similarly heightened slippage
      profile was also detected in rodents, another taxon exhibiting high diversity and
      rapid evolvability. The correlation of enhanced slippage rates with major
      evolutionary radiations suggests that the possession of a "slippery" genome may
      bestow on some taxa greater potential for rapid evolutionary change.

PMID- 17437959
TI  - First trimester maternal serum ischaemia-modified albumin: a marker of hypoxia
      ischaemia-driven early trophoblast development.
AB  - BACKGROUND: A hypoxic intrauterine environment is believed to play a pivotal role
      in physiological trophoblast development. Ischaemia-modified albumin (IMA) is
      used in the measurement of cardiac ischaemia. We aimed to test the hypothesis
      that maternal serum IMA may be elevated in early pregnancy as a measurable
      manifestation of intrauterine ischaemia. METHODS: Prospective observational study
      in healthy women with singleton pregnancies (n=66) and non-pregnant controls
      (n=26). Maternal serum IMA levels were measured at 11-13 weeks of gestation and
      in non-pregnant women. RESULTS: The median IMA level in the pregnant group
      [115.14 kU/l; interquartile range (IQR) 102.33-124.71 kU/l] was significantly
      higher (P<0.001) than in non-pregnant controls (73.71 kU/l; IQR 60.38-82.78
      kU/l). During pregnancy, absolute values of IMA were higher than the
      concentration used for the diagnosis of myocardial ischaemia (>95 kU/l) in 86% of
      women. CONCLUSIONS: In early pregnancy, IMA levels were above the concentration
      used for the diagnosis of myocardial ischaemia in most women, and should
      therefore not be used as a marker for cardiac ischaemia in pregnancy. Maternal
      serum IMA is elevated to supra-physiological levels in early normal pregnancy
      supporting the hypothesis that normal trophoblast development is associated with
      a hypoxic intrauterine environment, although other mechanisms leading to an IMA
      increase cannot be excluded.

PMID- 17437960
TI  - The number of small antral follicles (2-6 mm) determines the outcome of endocrine
      ovarian reserve tests in a subfertile population.
AB  - BACKGROUND: Ovarian reserve is related to age and can be estimated by ovarian
      reserve tests (ORTs), such as antral follicle count (AFC) and various endocrine
      parameters. The endocrine function of a follicle is related to its size. The aim
      of this study is to evaluate which sizes of antral follicles are most closely
      correlated with age and the outcome of endocrine ORTs. METHODS: In total 474
      subfertile, ovulatory patients, recruited from two fertility centers in The
      Netherlands, participated in this prospective cohort study. The following ORTs
      were performed: AFC (follicles from 2 to 10 mm), basal FSH, basal inhibin B
      (bInhB), clomiphene citrate challenge test and inhibin B after stimulation with
      clomiphene citrate. RESULTS: The number of small follicles (2-6 mm) declined with
      age; the number of larger follicles (7-10 mm) remained constant. Independent of
      age, the number of small follicles was significantly related to all ORTs
      (P<0.001, except bInhB P=0.005). The number of larger follicles was only
      significantly related to bInhB (P=0.009). CONCLUSIONS: The number of small antral
      follicles (2-6 mm) is significantly related to age and also, independent of age,
      to all endocrine ORTs tested, suggesting the number of small antral follicles
      represents the functional ovarian reserve.

PMID- 17437961
TI  - A role for tachykinins in the regulation of human sperm motility.
AB  - BACKGROUND: Tachykinins and tachykinin receptors are widely distributed in the
      male reproductive tract and appear to be involved in reproduction. However, the
      function and expression of tachykinins and their receptors in human spermatozoa
      remain poorly studied. We analysed the effects of tachykinins on sperm motility
      and characterized the population of tachykinin receptors in human spermatozoa.
      METHODS AND RESULTS: Motility analysis was performed following World Health
      Organization guidelines and we found that substance P (SP), human hemokinin-1
      (hHK-1), neurokinin A (NKA) and neurokinin B (NKB) produced concentration
      dependent increases in sperm progressive motility. The effects of tachykinins
      were antagonized by the NK(1) receptor-selective antagonist SR 140333, the NK(2)
      receptor-selective antagonist, SR 48968 and, to a lesser extent, also by the
      NK(3) receptor-selective antagonist SR 142801. Immunocytochemistry studies showed
      expression of the NK(1), NK(2) and NK(3) tachykinin receptor proteins in
      spermatozoa with different major sites of localization for each receptor. Western
      blot analysis confirmed the presence of tachykinin receptors in sperm cell
      homogenates. RT-PCR demonstrated expression of the genes that encode SP/NKA
      (TAC1), NKB (TAC3) and hHK-1 (TAC4) but not the genes TACR1, TACR2 and TACR3
      encoding NK(1), NK(2) and NK(3) receptors, respectively. CONCLUSIONS: These
      results show for the first time that the NK(1), NK(2) and NK(3) tachykinin
      receptor proteins are present in human spermatozoa. Our findings suggest that
      tachykinins, probably acting through these three tachykinin receptors, play a
      role in the regulation of human sperm motility.

PMID- 17437962
TI  - Effects of hydrophobic amino acid substitution in Pleurotus ostreatus proteinase
      A inhibitor 1 on its structure and functions as protease inhibitor and
      intramolecular chaperone.
AB  - We previously demonstrated that Pleurotus ostreatus proteinase A inhibitor 1
      (POIA1) could function as an intramolecular chaperone of subtilisin BPN', as in
      the case of the propeptide of subtilisin BPN', and that its Phe44 --> Ala mutant,
      which lost its tertiary structure, could not assist the refolding of subtilisin
      BPN'. In this study, we examined the effects of hydrophobic amino acid
      substitutions at other sites and substitutions of Phe44 with other hydrophobic
      residues on the structure and functions of POIA1. These mutations were introduced
      into POIA1cm that had been obtained by the substitution of the C-terminal six
      residues of POIA1 with those of the propeptide of subtilisin BPN'. When Ile32 or
      Ile64 was substituted with Ala, the tertiary structure of the resultant mutant
      was markedly destroyed, and the activities as a protease inhibitor and an
      intramolecular chaperone were significantly lowered. Among the position 44
      mutants, the Phe44 --> Val mutant was a much less effective intramolecular
      chaperone with conversion to a digestible inhibitor, possibly owing to
      destruction of the tertiary structure. On the other hand, the Phe44 --> Leu or
      Ile mutant maintained its tertiary structure, and hence could function as a more
      effective intramolecular chaperone than the Phe44 --> Val mutant. Furthermore,
      since the Phe44 --> Leu mutant was a more susceptible inhibitor than POIA1cm, the
      halo formed around a colony of Bacillus cells transformed with a plasmid encoding
      this mutant was larger than others. These results clearly show the close
      relationship between the tertiary structure and functions of POIA1 as a protease
      inhibitor and an intramolecular chaperone, and that a combination of such
      inhibitory properties and intramolecular chaperone activity of POIA1 might affect
      the diameter of the halo formed around Bacillus colonies in vivo.

PMID- 17437963
TI  - Comparison of Etest with agar dilution for testing the susceptibility of
      Pseudomonas aeruginosa and other multidrug-resistant bacteria to colistin.

PMID- 17437964
TI  - Abcg2/Bcrp1 mediates the polarized transport of antiretroviral nucleosides
      abacavir and zidovudine.
AB  - The bioavailability and targeted distribution of abacavir (ABC) and zidovudine
      (AZT) to viral reservoirs may be influenced by efflux transporters. The purpose
      of this study was to characterize the interaction of these nucleoside reverse
      transcriptase inhibitors with the Abcg2/Bcrp1 transporter, the murine homolog of
      human breast cancer resistance protein (BCRP), using a Bcrp1-transfected Madin
      Darby canine kidney II cell model. Intracellular accumulation of ABC and AZT was
      significantly reduced by approximately 90% and approximately 70%, respectively,
      in Bcrp1-transfected cells compared with the wild-type cells. Both ABC and AZT
      showed significantly increased basolateral-to-apical (B-to-A) and decreased
      apical-to-basolateral (A-to-B) transport in Bcrp1 cells compared with wild-type
      directional flux. The efflux ratio (ratio of B-to-A to A-to-B) in Bcrp1
      transfected cells was 22 for ABC and 11 for AZT. N-(4-[2-(1,2,3,4-tetrahydro-6,7
      dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine
      carboxamide (GF120918) inhibited this difference in accumulation between the two
      cell variants with an EC(50) of 1.32 +/- 0.3 microM for ABC and 0.31 +/- 0.1
      microM for AZT. Potent and highly cooperative inhibition by Ko143 (3-(6-isobutyl
      9-methoxy-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[1',2':1,6]pyrido[3,4
      b]indol-3-yl)-propionic acid tert-butyl ester) was observed with an EC(50) of 121
      +/- 5 nM for ABC and 19.2 +/- 1.5 nM for AZT (Hill coefficient approximately 3
      6). Probenecid, an organic anion inhibitor known to influence AZT
      biodistribution, had no effect on cellular accumulation in the Bcrp1 model. These
      studies characterize the Bcrp1-mediated transport of ABC and AZT and show that
      prototypical BCRP inhibitors GF120918 and Ko143 can inhibit the Bcrp1-mediated
      transport of these important antiretroviral compounds. The functional expression
      of BCRP at critical barriers, such as the intestinal enterocytes, brain capillary
      endothelium, and target lymphocytes, could influence the bioavailability and
      targeted delivery of these drugs to sanctuary sites.

PMID- 17437965
TI  - The prokinetic cinitapride has no clinically relevant pharmacokinetic interaction
      and effect on QT during coadministration with ketoconazole.
AB  - The present clinical trial was designed to evaluate the possible pharmacokinetic
      and electrocardiographic interactions of the gastroenteric prokinetic drug
      cinitapride with ketoconazole. The safety and tolerability of the study
      treatments were also evaluated. After a placebo-controlled, double-blind,
      crossover design, 16 healthy male (n = 8) and female (n = 8) volunteers were
      randomized into four treatment groups of four subjects (two males and two
      females): cinitapride (CTP; 1 mg t.i.d.) + ketoconazole (KET; 200 mg b.i.d.), CTP
      + placebo (PL), PL+KET, and PL+PL. Treatments were given for 7 days with a
      washout period of 14 days between crossover treatments. Cinitapride is rapidly
      absorbed after oral administration and is metabolized by the cytochrome P450
      CYP3A4 and CYP2C8 isozymes. At steady state, coadministration with ketoconazole,
      a potent CYP3A4 inhibitor, increased mean C(max,ss) and AUC(tau) by 1.63- and
      1.98-fold, respectively. Measurement of mean QTc interval or baseline-corrected
      QTc intervals on day 7 showed small increases that were due to the effects of
      ketoconazole alone. Comparing CTP+KET versus PL+KET, the differences between mean
      increases in the QTc parameters were always less than 2 ms. Finally, no outlier
      increase of the QTc interval versus baseline >60 ms was identified after any
      treatment. The study showed that cinitapride, either given alone or after
      coadministration with ketoconazole 200 mg b.i.d., had no effect on cardiac
      repolarization as measured by changes in the heart rate-corrected QT interval on
      the surface electrocardiogram.

PMID- 17437966
TI  - Successful coronary sinus lead placement after stenting of coronary vein
      stenosis.
AB  - In this paper, we describe a 62-year-old man with ischemic cardiomyopathy who
      underwent biventricular pacing and left ventricular lead could be implanted after
      stenting of a coronary vein stenosis.

PMID- 17437967
TI  - Prediction of sudden death in heart failure patients: a novel perspective from
      the assessment of the peak ectopy rate.
AB  - AIMS: In patients with heart failure (HF), the association between sudden death
      and arrhythmic pattern at 24-h Holter monitoring [number of ventricular premature
      contractions per hour (VPCs/h) and presence of non-sustained ventricular
      tachycardia (NSVT)] has previously been investigated with conflicting results.
      Since both VPCs/h and NSVT disregard the time course of arrhythmic events, we
      developed a new index based on the short-term peak rate of ectopies and
      investigated its prognostic power in HF patients. METHODS AND RESULTS: We studied
      200 HF patients in sinus rhythm [age: [median (interquartile range)] 54 years [47
      58], left ventricular ejection fraction (LVEF): 23% [19-28], New York Heart
      Association (NYHA) class II-III: 88%]. For each patient, the Holter recording was
      automatically scanned shifting a 30 beat window one beat at a time, and the
      maximum number of ectopic beats found in a window was named peak ectopy rate
      (PEAK_ER). The association between PEAK_ER and sudden death was assessed by Cox
      proportional hazards regression analysis. Survival analysis was also carried out
      adjusting for NYHA class, aetiology, LVEF, left ventricular end diastolic
      diameter, blood urea nitrogen, amiodarone, Digoxin, beta-blockers, NSVT, VPCs/h,
      and the standard deviation of all normal-to-normal beats. During a 5-year follow
      up [31 (12-60) months], 23 patients died of sudden death. Out of the arrhythmic
      markers, PEAK_ER but not VPCs/h and NSVT was significantly associated with sudden
      death in univariable analysis (RR: 1.08, 95% CI: 1.02-1.14, P = 0.005) and after
      adjustment for covariates (RR: 1.09, 95% CI: 1.03-1.15, P = 0.004). CONCLUSIONS:
      The investigation of the time course of arrhythmic events provides independent
      information in the identification of patients at increased risk of sudden death
      and may therefore be considered in the development of treatment strategies in HF
      patients.

PMID- 17437968
TI  - A multidisciplinary approach is required to increase the quality of phase II/III
      clinical studies on biotherapies in oncology.

PMID- 17437969
TI  - Identification and characterization of a new tom40 isoform, a central component
      of mitochondrial outer membrane translocase.
AB  - Newly synthesized precursors are transported into mitochondria through an outer
      membrane translocase, TOM. Tom40, a central pore-forming component, interacts
      directly with precursors to help them translocate across the outer membrane. We
      identified a new isoform of rat Tom40, Tom40B, which is conserved among mammals
      and exhibits significant similarities to Tom40 in other eukaryotes. Tom40B is an
      integral protein localized on the mitochondrial outer membrane, and expressed
      widely in all tissues examined except testis. Deletion mutant analysis revealed
      that the 28 amino acid residues at the carboxyl terminus were crucial for the
      mitochondrial targeting of Tom40B. Tom40B co-precipitated with other Tom
      components and formed a large protein complex. Furthermore, Tom40B directly bound
      to precursors of the matrix-targeted proteins with high affinities, comparable to
      those of Tom40A, a previously identified isoform. These findings indicate that
      Tom40B is a functional component of mitochondrial outer membrane translocase.

PMID- 17437970
TI  - Risk scores for risk stratification in acute coronary syndromes: useful but
      simpler is not necessarily better.
AB  - AIMS: Our objectives were (i) to compare the discriminatory performance of the
      Thrombolysis in Myocardial Infarction risk score (TIMI RS), Platelet glycoprotein
      IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy risk
      score (PURSUIT RS), and Global Registry of Acute Cardiac Events risk score (GRACE
      RS) for in-hospital and 1 year mortality across the broad spectrum of non-ST
      elevation acute coronary syndromes (ACS) and (ii) to determine their incremental
      prognostic utility beyond overall risk assessment by physicians. METHODS AND
      RESULTS: We calculated the TIMI RS, PURSUIT RS, and GRACE RS for 1,728 patients
      with non-ST-elevation ACS in the prospective, multicentre, Canadian ACS II
      Registry. Discriminatory performance was measured by the c-statistic (area under
      receiver-operating characteristic curve) and compared by the method described by
      DeLong. TIMI RS, PURSUIT RS, and GRACE RS all demonstrated good discrimination
      for in-hospital death (c-statistics = 0.68, 0.80, 0.81, respectively, all P <
      0.001) and 1 year mortality (c-statistics = 0.69, 0.77, 0.79, respectively, all P
      < 0.0001). However, PURSUIT RS and GRACE RS performed significantly better than
      the TIMI RS in predicting in-hospital (P = 0.036 and 0.02, respectively) and 1
      year (P = 0.006 and 0.001, respectively) outcomes. In multivariable analysis
      adjusting for the use of in-hospital revascularization, stratification by
      tertiles of risk scores (into low, intermediate, and high-risk groups) furnished
      independent and greater prognostic information compared with risk assessment by
      treating physicians for 1 year outcome. CONCLUSION: Compared with TIMI RS, both
      PURSUIT RS and GRACE RS allow better discrimination for in-hospital and 1 year
      mortality in patients presenting with a wide range of ACS. All three risk scores
      confer additional important prognostic value beyond global risk assessment by
      physicians. These validated risk scores may refine risk stratification, thereby
      improving patient care in routine clinical practice.

PMID- 17437972
TI  - Duplex arteriography for lower extremity revascularization.
AB  - Duplex arteriography may be a potential replacement of preoperative standard
      contrast arteriography for peripheral arterial imaging in lower extremity
      revascularization procedures. In patients with chronic or acute ischemia, a well
      performed duplex arteriography offers several practical advantages over contrast
      arteriography: it is noninvasive; it does not require nephrotoxic agents; it is
      portable and can be done expeditiously; color flow and waveform analysis provide
      a better estimation of the hemodynamic significance of occlusive disease; it
      allows direct visualization of the entire artery and not only of the lumen thus
      enabling plaque characterization; with color flow and power Doppler techniques,
      it is possible to identify patent arteries subjected to very low flow states; and
      it can detect occluded arterial aneurysms thereby avoiding unnecessary attempts
      at thromboembolectomies. High-quality arterial ultrasonography performed by a
      highly skilled and well-trained vascular technologist may represent an
      alternative to conventional arteriography for patients in need of primary or
      secondary lower extremity revascularization.

PMID- 17437973
TI  - Commentary on "Duplex arteriography for lower extremity revascularization".

PMID- 17437974
TI  - Duplex-guided balloon angioplasty of lower extremity arteries.
AB  - The conventional balloon angioplasty of infrainguinal arteries requires the use
      of fluoroscopy and injection of contrast material. We attempted to perform 360
      balloon angioplasties of the superficial femoral (SFA) and/or popliteal arteries
      under duplex guidance in 274 patients to avoid the nephrotoxic effect of contrast
      and eliminate or minimize radiation exposure. Critical ischemia was the
      indication in 35% of cases and severe claudication in 65%. Infrapopliteal
      angioplasties of 80 arteries were attempted in 54 cases (15% of all cases) in
      order to improve the run-off after completion of femoral-popliteal angioplasties.
      For femoral-popliteal segment, overall technical success was 95% (342/360 cases).
      For infrapopliteal arteries, technical success was achieved in 77 of 80 cases,
      with an overall success rate of 96%. Twelve-month patency rates for TASC class A,
      B, C, and D lesions were 90%, 59%, 52%, and 46%, respectively. PAVF <100 mL/min
      was the most powerful predictor of 30-day and 6-month arterial thrombosis
      following femoral/popliteal balloon angioplasties.Duplex-guided balloon
      angioplasty and stent placement appears to be a safe and effective technique for
      the treatment of femoral-popliteal and infrapopliteal arterial occlusive disease.
      PAVF <100 mL/min is the most powerful predictor of early (30 days) and midterm (6
      month) arterial thrombosis following femoral-popliteal interventions.

PMID- 17437975
TI  - Commentary on "Duplex-guided balloon angioplasty and stenting for occlusive and
      stenotic lesions of the infrainguinal arteries".

PMID- 17437976
TI  - Treatment of failing lower extremity arterial bypasses under ultrasound guidance.
AB  - Endovascular repair of failing infrainguinal bypasses can effectively improve
      patency and limb salvage results in selected cases. We attempted to perform
      balloon angioplasties of 47 failing grafts in 3 patients under duplex guidance to
      eliminate or diminish the use of nephrotoxic contrast material and radiation
      exposure. The technical success was 98% (46/47 cases). One case of the outflow
      lesion in the plantar artery could not be traversed with the guidewire due to
      extreme tortuosity. Overall local complications rate was 4% (2 cases). One vein
      bypass pseudoaneurysm caused by rupture with cutting balloon was repaired by
      patch angioplasty and 1 SFA pseudoaneurysm at the puncture site required open
      repair. Overall 6- and 12-month primary patency rates were 70% and 50%,
      respectively.Duplex guidance of failing infrainguinal arterial bypasses appears
      to be an effective treatment modality. Advantages include visualization of the
      puncture site, accurate selection of the proper size balloon, and confirmation of
      the adequacy of the technique by hemodynamic and imaging parameters. Additional
      benefits are avoidance of radiation exposure and contrast material in most cases.

PMID- 17437977
TI  - Commentary on "Treatment of failing lower extremity arterial bypasses under
      ultrasound guidance".

PMID- 17437978
TI  - Duplex-assisted internal carotid artery balloon angioplasty and stent placement.
AB  - Carotid artery balloon angioplasty and stenting (CBAS) is gaining popularity as
      an adequate alternative to carotid endarterectomy (CEA) in selected patients.
      Unfortunately, the substantial amount of contrast media used for CBAS,
      traditionally performed under fluoroscopic guidance, may impair renal function in
      patients with diabetes or ones with elevated serum creatinine. We attempted to
      apply duplex assistance to limit or eliminate the use of contrast during CBAS.
      Fluoroscopy was utilized to assist manipulation of the guidewire into the aorta
      and the common carotid artery, and positioning of the distal cerebral protection
      device. Selective catheterization of the internal and external carotid arteries
      was performed under ultrasound guidance. Balloons and stent were successfully
      deployed with ultrasound guidance alone in all cases. Appropriate stent
      apposition and arterial patency were confirmed by duplex in all cases. One
      ipsilateral stroke (2.9%) occurred intraoperatively with almost complete clinical
      recovery in 4 months. On-table biplanar cerebral arteriogram performed in this
      patient was normal. No early (30-day) mortalities were in the series. Duplex
      assisted CBAS is feasible and may reduce the need for contrast media in selected
      patients with high risk for renal failure. Additional advantages include guidance
      of the femoral puncture, precise position of the balloon and stent and B-mode and
      hemodynamic confirmation of the adequacy of the technique.

PMID- 17437979
TI  - Commentary on "Duplex-assisted internal carotid artery balloon angioplasty and
      stent placement".

PMID- 17437980
TI  - Duplex-guided repair of failing or nonmaturing arterio-venous access for
      hemodialysis.
AB  - Diagnostic arteriography and balloon angioplasty of failing or nonmaturing
      arterio-venous (AV) access is based upon using nephrotoxic contrast. Patients not
      yet on dialysis with borderline renal function with nonmaturing AV accesses or
      ones with an allergy to contrast media present a therapeutic challenge. We have
      used duplex scanning as an alternative imaging modality to guide endovascular
      therapy in 10 cases (9 autologous and 1 prosthetic). Six target AV accesses (60%)
      were used for dialysis. Number of stenoses ranged from 1 to 5 per AV access.
      Short access sheath insertion, wire and balloon passage, and inflation were
      guided by duplex only. Balloon size (5-8 mm in diameter) was chosen based on
      duplex measurements. Cutting balloons (4 x 20 mm and 5 x 20 mm) were used for
      dilatation of recoiling lesions in 4 cases. One patient had a self-expanding
      stent placed under duplex-guidance for recoiling lesion in the junction of the
      brachial and axillary veins. Angioplasty of failing AV access can be performed
      under duplex guidance alone. Duplex guidance offers very important advantages of
      hemodynamic evaluation for recoiling lesions and need for stenting. Avoidance of
      contrast use for repair of nonfunctioning AV access can be a useful option in
      patients with renal failure not yet on dialysis or in cases of allergy.

PMID- 17437981
TI  - Commentary on "Duplex-guided repair of failing or nonmaturing arterio-venous
      access for hemodialysis".

PMID- 17437982
TI  - Diagnosis and management of pseudoaneurysms.
AB  - Pseudoaneurysms develop at the site of arterial access when there is failure to
      establish adequate hemostasis. The number of percutaneous diagnostic and
      therapeutic coronary and peripheral vascular interventions has increased and with
      it a commensurate rise in the incidence of pseudoaneurysms is observed. Clinical
      examination and color-flow duplex ultrasound identify the majority of
      pseudoaneurysms. Ultrasound-guided thrombin injection has been shown to be the
      ideal method to treat the vast majority of false aneurysms. In a small number of
      cases, alternative endovascular techniques or open surgical repair is required.

PMID- 17437983
TI  - Commentary on "Diagnosis and management of pseudoaneurysms".

PMID- 17437984
TI  - Reflux testing and imaging for endovenous ablation.
AB  - Endovenous ablation is a newer therapy for treating superficial veins in patients
      with chronic venous disease. The saphenous veins and their accessory veins can be
      treated. Radiofrequency and laser energy are used to ablate the veins. Accurate
      ultrasound mapping is needed to plan and perform these procedures. The length and
      the number of the veins treated are determined. The diameter of the vein, its
      distance from the skin, and segments with tortuosity, thrombosis, and anatomic
      variations are documented. During the procedure the access in the vein, and the
      introduction of the wire, sheath, catheter, and tumescent anesthesia are done
      under ultrasound guidance. The success of the procedures and the complications
      are monitored. In most studies, the failure rate is 10% or less at 2 years, and
      the prevalence of deep vein thrombosis is less than 3%. Currently, endovenous
      ablation has become the method of choice for treating superficial veins and it
      has almost replaced the traditional ligation and stripping.

PMID- 17437985
TI  - Commentary on "Reflux testing and imaging for endovenous ablation".

PMID- 17437986
TI  - Radiofrequency ablation of incompetent perforator veins.
AB  - Chronic venous insufficiency continues to be a major source of disability and
      cost, with accompanying socio-economic burdens. Incompetent perforator veins play
      a significant role in chronic venous insufficiency. This article describes the
      technique of radiofrequency ablation of incompetent perforating veins for
      patients with chronic venous insufficiency. Patient evaluation, the evolution of
      the treatment technique, and details of current treatment are provided.
      Radiofrequency ablation of incompetent perforating veins is feasible, has
      promising early results, and extends the armamentarium of minimally invasive
      venous treatments.

PMID- 17437987
TI  - The bedside insertion of inferior vena cava filters using ultrasound guidance.
AB  - Since the introduction of inferior vena cava (IVC) filters more than 30 years
      ago, there has been a steady improvement in the design, ease, and safety of the
      delivery systems. Today, all of the commonly used filters can be placed via a
      peripheral vein by using standard percutaneous Seldinger technique. However, this
      typically requires fluoroscopy, intravenous contrast agents, radiation exposure,
      and transport of the patient to the interventional or operating suite. In the
      multiply injured trauma or critically-ill intensive care unit patient, often
      requiring inotropic and ventilator support, transport to these facilities can be
      hazardous. In addition, these patients frequently have a combination of
      neurospinal and long bone injuries, which require skeletal immobilization, thus
      further complicating transportation. Advancing technology with portable duplex
      ultrasound and improved deep abdominal duplex imaging has allowed for routine
      diagnostic evaluation of the IVC, renal veins, and surrounding visceral
      structures. This degree of accuracy has allowed numerous centers to gain
      experience with ultrasonic imaging of the IVC and insertion site after a filter
      has been placed. A logical progression has evolved to the point in which, today,
      duplex ultrasound can be used to guide the insertion of IVC filters. The
      following describes, in detail, a technique for the percutaneous placement of an
      IVC filter at the bedside using only duplex ultrasound guidance. The article also
      briefly compares and contrasts this technique with an alternate technique using
      intravascular ultrasound. Vena caval interruption can be safely performed under
      ultrasound guidance in a monitored, intensive care unit environment. In selected
      intensive care unit or multiply injured trauma patients, this will reduce the
      risk, complexity and cost of transport for these critically ill patients. Duplex
      guided IVC filter placement also reduces procedural costs compared to an
      operating room or interventional suite, and eliminates intravenous contrast
      material exposure.

PMID- 17437988
TI  - Commentary on "The bedside insertion of inferior vena cava filters using
      ultrasound guidance".

PMID- 17437989
TI  - Commentary. Aspirin plus dipyridamole versus aspirin alone after cerebral
      ischaemia of arterial origin (ESPRIT): randomised controlled trial.

PMID- 17437990
TI  - Mechanistic insights and identification of two novel factors in the C. elegans
      NMD pathway.
AB  - The nonsense-mediated mRNA decay (NMD) pathway selectively degrades mRNAs
      harboring premature termination codons (PTCs). Seven genes (smg-1-7, for
      suppressor with morphological effect on genitalia) that are essential for NMD
      were originally identified in the nematode Caenorhabditis elegans, and orthologs
      of these genes have been found in several species. Whereas in humans NMD is
      linked to splicing, PTC definition occurs independently of exon boundaries in
      Drosophila. Here, we have conducted an analysis of the cis-acting sequences and
      trans-acting factors that are required for NMD in C. elegans. We show that a PTC
      codon is defined independently of introns in C. elegans and, consequently,
      components of the exon junction complex (EJC) are dispensable for NMD. We also
      show a distance-dependent effect, whereby PTCs that are closer to the 3' end of
      the mRNA are less sensitive to NMD. We also provide evidence for the existence of
      previously unidentified components of the NMD pathway that, unlike known smg
      genes, are essential for viability in C. elegans. A genome-wide RNA interference
      (RNAi) screen resulted in the identification of two such novel NMD genes, which
      are essential for proper embryonic development, and as such represent a new class
      of essential NMD genes in C. elegans that we have termed smgl (for smg lethal).
      We show that the encoded proteins are conserved throughout evolution and are
      required for NMD in C. elegans and also in human cells.

PMID- 17437991
TI  - The tumor suppressor microRNA let-7 represses the HMGA2 oncogene.
AB  - HMGA2, a high-mobility group protein, is oncogenic in a variety of tumors,
      including benign mesenchymal tumors and lung cancers. Knockdown of Dicer in HeLa
      cells revealed that the HMGA2 gene is transcriptionally active, but its mRNA is
      destabilized in the cytoplasm through the microRNA (miRNA) pathway. HMGA2 was
      derepressed upon inhibition of let-7 in cells with high levels of the miRNA.
      Ectopic expression of let-7 reduced HMGA2 and cell proliferation in a lung cancer
      cell. The effect of let-7 on HMGA2 was dependent on multiple target sites in the
      3' untranslated region (UTR), and the growth-suppressive effect of let-7 on lung
      cancer cells was rescued by overexpression of the HMGA2 ORF without a 3'UTR. Our
      results provide a novel example of suppression of an oncogene by a tumor
      suppressive miRNA and suggest that some tumors activate the oncogene through
      chromosomal translocations that eliminate the oncogene's 3'UTR with the let-7
      target sites.

PMID- 17437992
TI  - The transcription factor HIF-1alpha plays a critical role in the growth factor
      dependent regulation of both aerobic and anaerobic glycolysis.
AB  - Mammalian cells are believed to have a cell-intrinsic ability to increase glucose
      metabolism in response to hypoxia. Here we show that the ability of hematopoietic
      cells to up-regulate anaerobic glycolysis in response to hypoxia is dependent on
      receptor-mediated signal transduction. In the absence of growth factor signaling,
      hematopoietic cells fail to express hypoxia-inducible transcription factor (Hif
      1alpha) mRNA. Growth factor-deprived hematopoietic cells do not engage in glucose
      dependent anabolic synthesis and neither express Hif-1alpha mRNA nor require HIF
      1alpha protein to regulate cell survival in response to hypoxia. However, HIF
      1alpha is adaptive for the survival of growth factor-stimulated cells, as
      suppression of HIF-1alpha results in death when growing cells are exposed to
      hypoxia. Growth factor-dependent HIF-1alpha expression reprograms the
      intracellular fate of glucose, resulting in decreased glucose-dependent anabolic
      synthesis and increased lactate production, an effect that is enhanced when HIF
      1alpha protein is stabilized by hypoxia. Together, these data suggest that HIF
      1alpha contributes to the regulation of growth factor-stimulated glucose
      metabolism even in the absence of hypoxia.

PMID- 17437993
TI  - Pharmacologic disruption of Polycomb-repressive complex 2-mediated gene
      repression selectively induces apoptosis in cancer cells.
AB  - Polycomb-repressive complex 2 (PRC2)-mediated histone methylation plays an
      important role in aberrant cancer gene silencing and is a potential target for
      cancer therapy. Here we show that S-adenosylhomocysteine hydrolase inhibitor 3
      Deazaneplanocin A (DZNep) induces efficient apoptotic cell death in cancer cells
      but not in normal cells. We found that DZNep effectively depleted cellular levels
      of PRC2 components EZH2, SUZ12, and EED and inhibited associated histone H3 Lys
      27 methylation (but not H3 Lys 9 methylation). By integrating RNA interference
      (RNAi), genome-wide expression analysis, and chromatin immunoprecipitation (ChIP)
      studies, we have identified a prominent set of genes selectively repressed by
      PRC2 in breast cancer that can be reactivated by DZNep. We further demonstrate
      that the preferential reactivation of a set of these genes by DZNep, including a
      novel apoptosis affector, FBXO32, contributes to DZNep-induced apoptosis in
      breast cancer cells. Our results demonstrate the unique feature of DZNep as a
      novel chromatin remodeling compound and suggest that pharmacologic reversal of
      PRC2-mediated gene repression by DZNep may constitute a novel approach for cancer
      therapy.

PMID- 17437994
TI  - Single- and double-stranded DNA: building a trigger of ATR-mediated DNA damage
      response.

PMID- 17437995
TI  - Hippo signaling in organ size control.
AB  - The control of organ (or organism) size is a fundamental aspect of life that has
      long captured human imagination. What makes an elephant grow a million times
      larger than a mouse? How do our two hands develop independently of each other yet
      reach very similar size? How does a liver precisely regenerate its original mass
      when two-thirds of it is removed? The recent discovery of a novel signaling
      network in Drosophila, known as the Hippo (Hpo) pathway, might provide an
      important entry point to these fascinating questions. The Hpo pathway consists of
      several negative growth regulators acting in a kinase cascade that ultimately
      phosphorylates and inactivates Yorkie (Yki), a transcriptional coactivator that
      positively regulates cell growth, survival, and proliferation. Components of the
      Hpo pathway are highly conserved throughout evolution, suggesting that this
      pathway may function as a global regulator of tissue homeostasis in all metazoan
      animals. Here, I provide a historical review of this potent growth-regulatory
      pathway and highlight outstanding questions that will likely be the focus of
      future investigation.

PMID- 17437996
TI  - The structural determinants of checkpoint activation.
AB  - Here, we demonstrate that primed, single-stranded DNA (ssDNA) is sufficient for
      activation of the ATR-dependent checkpoint pathway in Xenopus egg extracts. Using
      this structure, we define the contribution of the 5'- and 3'-primer ends to Chk1
      activation when replication is blocked and ongoing. In addition, we show that
      although ssDNA is not sufficient for checkpoint activation, the amount of ssDNA
      adjacent to the primer influences the level of Chk1 phosphorylation. These
      observations define the minimal DNA requirements for checkpoint activation and
      suggest that primed ssDNA represents a common checkpoint activating-structure
      formed following many types of damage.

PMID- 17437997
TI  - SirT3 is a nuclear NAD+-dependent histone deacetylase that translocates to the
      mitochondria upon cellular stress.
AB  - In humans, there are at least seven Sir2-like proteins (SirT1-7) with diverse
      functions, including the regulation of chromatin structure, and metabolism. SirT3
      levels have been shown to correlate with extended life span, to localize to the
      mitochondria, and to be highly expressed in brown adipose tissue. In humans,
      SirT3 exists in two forms, a full-length protein of approximately 44 kDa and a
      processed polypeptide lacking 142 amino acids at its N terminus. We found that
      SirT3 not only localizes to the mitochondria, but also to the nucleus under
      normal cell growth conditions. Both the full-length and processed forms of SirT3
      target H4-K16 for deacetylation in vitro and can deacetylate H4-K16 in vivo when
      recruited to a gene. Using a highly specific antibody against the N terminus of
      SirT3, we found that SirT3 is transported from the nucleus to the mitochondria
      upon cellular stress. This includes DNA damage induced by Etoposide and UV
      irradiation, as well as overexpression of SirT3 itself.

PMID- 17437998
TI  - Single-stranded DNA-binding proteins regulate the abundance of LIM domain and LIM
      domain-binding proteins.
AB  - The LIM domain-binding protein Ldb1 is an essential cofactor of LIM-homeodomain
      (LIM-HD) and LIM-only (LMO) proteins in development. The stoichiometry of Ldb1,
      LIM-HD, and LMO proteins is tightly controlled in the cell and is likely a
      critical determinant of their biological actions. Single-stranded DNA-binding
      proteins (SSBPs) were recently shown to interact with Ldb1 and are also important
      in developmental programs. We establish here that two mammalian SSBPs, SSBP2 and
      SSBP3, contribute to an erythroid DNA-binding complex that contains the
      transcription factors Tal1 and GATA-1, the LIM domain protein Lmo2, and Ldb1 and
      binds a bipartite E-box-GATA DNA sequence motif. In addition, SSBP2 was found to
      augment transcription of the Protein 4.2 (P4.2) gene, a direct target of the E
      box-GATA-binding complex, in an Ldb1-dependent manner and to increase endogenous
      Ldb1 and Lmo2 protein levels, E-box-GATA DNA-binding activity, and P4.2 and beta
      globin expression in erythroid progenitors. Finally, SSBP2 was demonstrated to
      inhibit Ldb1 and Lmo2 interaction with the E3 ubiquitin ligase RLIM, prevent RLIM
      mediated Ldb1 ubiquitination, and protect Ldb1 and Lmo2 from proteasomal
      degradation. These results define a novel biochemical function for SSBPs in
      regulating the abundance of LIM domain and LIM domain-binding proteins.

PMID- 17438000
TI  - CHD4/Mi-2beta activity is required for the positioning of the
      mesoderm/neuroectoderm boundary in Xenopus.
AB  - Experiments in Xenopus have illustrated the importance of extracellular
      morphogens for embryonic gene regulation in vertebrates. Much less is known about
      how induction leads to the correct positioning of boundaries; for example,
      between germ layers. Here we report that the neuroectoderm/mesoderm boundary is
      controlled by the chromatin remodeling ATPase CHD4/Mi-2beta. Gain and loss of
      CHD4 function experiments shifted this boundary along the animal-vegetal axis at
      gastrulation, leading to excess mesoderm formation at the expense of
      neuroectoderm, or vice versa. This phenotype results from specific alterations in
      gene transcription, notably of the neural-promoting gene Sip1 and the mesodermal
      regulatory gene Xbra. We show that CHD4 suppresses Sip1 transcription by direct
      binding to the 5' end of the Sip1 gene body. Furthermore, we demonstrate that
      CHD4 and Sip1 expression levels determine the "ON" threshold for Nodal-dependent
      but not for eFGF-dependent induction of Xbra transcription. The CHD4/Sip1
      epistasis thus constitutes a regulatory module, which balances mesoderm and
      neuroectoderm formation.

PMID- 17437999
TI  - Polycomb genes interact with the tumor suppressor genes hippo and warts in the
      maintenance of Drosophila sensory neuron dendrites.
AB  - Dendritic fields are important determinants of neuronal function. However, how
      neurons establish and then maintain their dendritic fields is not well
      understood. Here we show that Polycomb group (PcG) genes are required for
      maintenance of complete and nonoverlapping dendritic coverage of the larval body
      wall by Drosophila class IV dendrite arborization (da) neurons. In esc, Su(z)12,
      or Pc mutants, dendritic fields are established normally, but class IV neurons
      display a gradual loss of dendritic coverage, while axons remain normal in
      appearance, demonstrating that PcG genes are specifically required for dendrite
      maintenance. Both multiprotein Polycomb repressor complexes (PRCs) involved in
      transcriptional silencing are implicated in regulation of dendrite arborization
      in class IV da neurons, likely through regulation of homeobox (Hox) transcription
      factors. We further show genetic interactions and association between PcG
      proteins and the tumor suppressor kinase Warts (Wts), providing evidence for
      their cooperation in multiple developmental processes including dendrite
      maintenance.

PMID- 17438001
TI  - CARMA3 deficiency abrogates G protein-coupled receptor-induced NF-{kappa}B
      activation.
AB  - G protein-coupled receptors (GPCRs) play pivotal roles in regulating various
      cellular functions. Although many GPCRs induce NF-kappaB activation, the
      molecular mechanism of GPCR-induced NF-kappaB activation remains largely unknown.
      CARMA3 (CARD and MAGUK domain-containing protein 3) is a scaffold molecule with
      unknown biological functions. By generating CARMA3 knockout mice using the gene
      targeting approach, here we show CARMA3 is required for GPCR-induced NF-kappaB
      activation. Mechanistically, we found that CARMA3 deficiency impairs GPCR-induced
      IkappaB kinase (IKK) activation, although it does not affect GPCR-induced
      IKKalpha/beta phosphorylation, indicating that inducible phosphorylation of
      IKKalpha/beta alone is not sufficient to induce its kinase activity. We also
      found that CARMA3 is physically associated with NEMO/IKKgamma, and induces
      polyubiquitination of an unknown protein(s) that associates with NEMO, likely by
      linking NEMO to TRAF6. Consistently, we found TRAF6 deficiency also abrogates
      GPCR-induced NF-kappaB activation. Together, our results provide the genetic
      evidence that CARMA3 is required for GPCR-induced NF-kappaB activation.

PMID- 17438002
TI  - SWI/SNF is required for transcriptional memory at the yeast GAL gene cluster.
AB  - Post-translational modification of nucleosomal histones has been suggested to
      contribute to epigenetic transcriptional memory. We describe a case of
      transcriptional memory in yeast where the rate of transcriptional induction of
      GAL1 is regulated by the prior expression state. This epigenetic state is
      inherited by daughter cells, but does not require the histone acetyltransferase,
      Gcn5p, the histone ubiquitinylating enzyme, Rad6p, or the histone methylases,
      Dot1p, Set1p, or Set2p. In contrast, we show that the ATP-dependent chromatin
      remodeling enzyme, SWI/SNF, is essential for transcriptional memory at GAL1.
      Genetic studies indicate that SWI/SNF controls transcriptional memory by
      antagonizing ISWI-like chromatin remodeling enzymes.

PMID- 17438003
TI  - Are we overestimating left ventricular abnormalities in end-stage renal disease?

PMID- 17438005
TI  - Erythropoietin ameliorates renal dysfunction during endotoxaemia.
AB  - BACKGROUND: Sepsis has a high mortality (50-80%) when associated with acute renal
      failure (ARF). Oxidant injury and proinflammatory cytokines and chemokines have
      been shown to increase with endotoxaemia-related ARF. Since erythropoietin (EPO)
      has been demonstrated to possess anti-oxidant and anti-inflammatory properties,
      EPO may have therapeutic efficacy for treating ARF associated with endotoxaemia.
      METHODS: Wild-type mice were given 2.5 mg/kg of intraperitoneal (i.p.) endotoxin,
      lipopolysaccharide (LPS), and studied 16 h later. Thirty minutes prior to LPS,
      the mice were given either EPO or vehicle. RESULTS: During endotoxaemia, EPO was
      found to significantly attenuate the renal dysfunction, as assessed by glomerular
      filtration rate (48.1 +/- 12.4 microl/min vs 136.7 +/- 30.2, P < 0.05). Renal
      blood flow and mean arterial pressure were not significantly different between
      the two groups. The renal dysfunction during endotoxaemia was associated with a
      decrease in renal superoxide dismutase (SOD). The EPO-related renal protection
      was associated with reversal of the effects of endotoxin on renal SOD.
      CONCLUSION: This is the first demonstration of a renal protective effect of EPO
      on endotoxin-related renal dysfunction.

PMID- 17438006
TI  - Insulin resistance and muscle wasting in non-diabetic end-stage renal disease
      patients.
AB  - BACKGROUND: Insulin resistance (IR) is prevalent in uraemia. Recent experimental
      studies suggested IR to be a central mechanism for uraemic malnutrition. However,
      it is not known whether IR is related to muscle wasting in non-diabetic end-stage
      renal disease (ESRD) patients. METHODS: We cross-sectionally assessed IR and
      muscle wasting in 21 non-diabetic ESRD patients who admitted for the initiation
      of dialysis. For the assessment of muscle wasting, lean body mass was measured
      (LBMm) by dual energy X-ray absorptiometry and compared with the estimated LBM
      (LBMe) from the prediction equation derived from healthy controls using the ratio
      of LBMm/LBMe. For measurement of IR, the homoeostasis model (HOMA-IR) was used.
      In addition, among patients who chose continuous ambulatory peritoneal dialysis,
      muscle was sampled during catheter insertion from the rectus abdominis to measure
      14-kDa actin fragments, a marker of muscle protein degradation. RESULTS: Patients
      with a low LBMm/LBMe ratio (<1.00) showed higher HOMA-IR and fat mass (FM) (%
      body weight) and lower LBM (% body weight) than those with a high LBMm/LBMe ratio
      (>or=1.00). LBMm/LBMe ratio was negatively correlated with HOMA-IR, regardless of
      obesity. By multiple regression analysis, HOMA-IR was an independent factor
      affecting LBMm/LBMe ratio. Furthermore, in the muscle samples, patients with high
      HOMA-IR had lower LBMm/LBMe ratios and stronger bands for the 14-kDa actin
      fragments than did patients with low HOMA-IR. CONCLUSION: These results suggest
      that IR seems to be associated with muscle wasting in non-diabetic ESRD patients.

PMID- 17438007
TI  - Somatic mutations of the von Hippel-Lindau disease gene in renal carcinomas
      occurring in patients with long-term dialysis.
AB  - BACKGROUND: Renal cell carcinoma (RCC) frequently occurs in patients with long
      term dialysis. Long-term dialysis causes distinctive pathological changes in the
      kidney, which is known as acquired cystic disease of the kidney (ACDK). It is of
      great interest to know whether RCCs occurring in the dialytic kidneys harbour the
      same or similar mutations of the von Hippel-Lindau (VHL) gene as conventional
      dialysis-unrelated clear cell RCCs so often do. METHODS: Renal cancer tissues
      (eight clear cell, two papillary, one Bellini duct and three of the so-called
      dialysis-specific renal carcinomas) from 13 patients undergoing long-term
      dialysis were examined for somatic mutations of the VHL disease gene. By means of
      laser capture microdissection, cancerous and surrounding non-cancerous renal
      tissues from dialytic patients were subjected to PCR-based direct sequencing of
      the VHL gene. RESULTS: Direct forward and reverse sequencing showed that three
      tumours possessed VHL gene mutations (713delG, 500-504del5-bp and 709A>G). These
      three mutations were identified in clear cell carcinomas occurring in association
      with end-stage renal disease undergoing dialysis for 194, 147 and 125 months.
      None of the non-tumour tissues or other carcinoma tissues analysed, including
      dialysis-specific carcinoma, possessed VHL gene mutations. CONCLUSION: These
      results indicate that VHL tumour-suppressor gene mutation is involved in clear
      cell carcinoma in association with long-term dialysis. Mutation of the VHL gene
      was not found in any of the dialysis-specific RCCs studied herein.

PMID- 17438008
TI  - A ten-year single-centre experience in children on chronic peritoneal dialysis-
      significance of percutaneous placement of peritoneal dialysis catheters.
AB  - BACKGROUND: Chronic peritoneal dialysis (CPD) in children is an important
      modality of renal replacement therapy. The ideal method for inserting CPD
      catheters remains still controversial. Minimal invasive techniques are becoming
      more popular. This study was performed in order to evaluate the efficiency, the
      complication profile and the survey of percutaneously placed CPD catheters in
      children, retrospectively. METHODS: This study was carried out on 108 peritoneal
      catheters implanted in 93 patients (45 girls, 48 boys), aged 8.0+/-4.2 years
      (range: 3 months to 16 years) during the period between December 1995 and
      November 2005. In the study group, 32 children were transplanted, 15 were
      transferred to haemodialysis and 18 patients died. All catheters implanted by
      percutaneous route were Tenckhoff swan-neck double-cuff paediatric catheters.
      Placement procedure was performed in our unit by us. Statistical analysis was
      made by chi-square and Kaplan-Meier methods. RESULTS: During 2670 CPD months we
      observed a total of 108 catheter-related complications: 82 catheter infections
      including exit-site and/or tunnel infection (1/32.5 patient-months), 10
      dislocations, six drainage problems and six kinks. The incidence of all
      complications was one complication every 24.72 dialysis months. Overall, the
      incidence of peritonitis was one episode per 18.1 patient-months. Pseudomonas
      spp. and Staphylococcus aureus were the two most common causes of infections.
      Fifteen catheters were removed due to catheter-related causes: drainage problems
      (six patients), catheter dislocation (three patients), omental capture (two
      patients) kink (two patients) and tunnel infection (two patients). The catheter
      survival rate was 92.4% at 1 year, 83% at 2 years and 63% at 10 years; patient
      survival in the 93 children was 91% at 1 year, 84% at 2 years and 48% at 10
      years. Younger patients were at increased risk of exit-site and tunnel infections
      (P<0.05) but the difference in catheter survival time between the age groups was
      not significant (P>0.05). In complications, no statistical difference was
      observed between early and delayed catheter use groups (P>0.05). We compared the
      two periods (period 1, December 1995 to November 2000; period 2, December 2000 to
      November 2005), for complications of CPD. The risk of catheter migration was
      greater in period 1 than in period 2 (P=0.04). CONCLUSIONS: The percutaneous
      technique performed by experienced nephrologists is a reliable, safe and cost
      effective method for placement of PD catheters. In our opinion, the skill for CPD
      catheter placement must be part of the paediatric nephrologist training.

PMID- 17438009
TI  - Effect of JNK inhibition on cisplatin-induced renal damage.
AB  - BACKGROUND: Cisplatin therapy is effective against many tumours, however, the
      nephrotoxicity of this drug is a dose-limiting factor. Apoptosis and necrosis of
      tubular cells and inflammatory events contribute to the cisplatin-induced
      nephrotoxicity. Cisplatin promotes increased production of reactive oxygen
      species, which can activate c-jun N-terminal kinase (JNK) that is a mediator of
      apoptosis and can lead to increased expression of proinflammatory mediators that
      could intensify the cytotoxic effects of cisplatin. In this study, we evaluated
      the effect that SP600125, a selective inhibitor of phosphorylated JNK (p-JNK),
      has on the renal damage caused by cisplatin use. METHODS: A total of 33 male
      Wistar rats received SP600125 (15 mg/kg/day, s.c., diluted in polyethylene
      glycol) for 4 days. At 24 h after the first dose, those 33 rats, plus an
      additional 30, were injected with cisplatin (5 mg/kg, i.p.). In addition, 18
      control rats were injected with saline, and 12 rats with polyethylene glycol. At
      2 and 5 days after saline or cisplatin injection, blood and urine samples were
      collected for measurement of creatinine, sodium and potassium, and the kidneys
      removed for histological, immunohistochemical and Western blot studies. RESULTS:
      Cisplatin-treated rats presented higher plasma creatinine, as well as greater
      immunostaining for ED1 (macrophages/monocytes), p-JNK, apoptotic cells, and
      tubular cell necrosis in the renal cortices and outer medullae. The increase of p
      JNK expression was also confirmed by Western blot analysis. All of these
      alterations were attenuated by treatment with SP600125. CONCLUSION: The
      protective effect of SP600125 on cisplatin-induced renal damage seems to be
      related to the reduction in the apoptotic cell death and to the restriction of
      renal inflammation.

PMID- 17438010
TI  - Atherogenesis and inflammation--was Virchow right?

PMID- 17438011
TI  - The A467T and W748S POLG substitutions are a rare cause of adult-onset ataxia in
      Europe.

PMID- 17438014
TI  - Sir Charles Sherrington's the integrative action of the nervous system: a
      centenary appreciation.
AB  - In 1906 Sir Charles Sherrington published The Integrative Action of the Nervous
      System, which was a collection of ten lectures delivered two years before at Yale
      University in the United States. In this monograph Sherrington summarized two
      decades of painstaking experimental observations and his incisive interpretation
      of them. It settled the then-current debate between the "Reticular Theory" versus
      "Neuron Doctrine" ideas about the fundamental nature of the nervous system in
      mammals in favor of the latter, and it changed forever the way in which
      subsequent generations have viewed the organization of the central nervous
      system. Sherrington's magnum opus contains basic concepts and even terminology
      that are now second nature to every student of the subject. This brief article
      reviews the historical context in which the book was written, summarizes its
      content, and considers its impact on Neurology and Neuroscience.

PMID- 17438015
TI  - Promoting anatomical plasticity and recovery of function after traumatic injury
      to the central or peripheral nervous system.

PMID- 17438016
TI  - Adeno-associated virus-mediated L1 expression promotes functional recovery after
      spinal cord injury.
AB  - Paucity of permissive molecules and abundance of inhibitory molecules in the
      injured spinal cord of adult mammals prevent axons from successful regeneration
      and, thus, contribute to the failure of functional recovery. Using an adeno
      associated viral (AAV) vector, we expressed the regeneration-promoting cell
      adhesion molecule L1 in both neurons and glia in the lesioned spinal cord of
      adult mice. Exogenous L1, detectable already 1 week after thoracic spinal cord
      compression and immediate vector injection, was expressed at high levels up to 5
      weeks, the longest time-period studied. Dissemination of L1-transduced cells
      throughout the spinal cord was wide, spanning over more than 10 mm rostral and 10
      mm caudal to the lesion scar. L1 was not detectable in the fibronectin-positive
      lesion core. L1 overexpression led to improved stepping abilities and muscle
      coordination during ground locomotion over a 5-week observation period. Superior
      functional improvement was associated with enhanced reinnervation of the lumbar
      spinal cord by 5-HT axons. Corticospinal tract axons did not regrow beyond the
      lesion scar but extended distally into closer proximity to the injury site in AAV
      L1-treated compared with control mice. The expression of the neurite outgrowth
      inhibitory chondroitin sulphate proteoglycan NG2 was decreased in AAV-L1-treated
      spinal cords, along with reduction of the reactive astroglial marker GFAP. In
      vitro experiments confirmed that L1 inhibits astrocyte proliferation, migration,
      process extension and GFAP expression. Analyses of intracellular signalling
      indicated that exogenous L1 activates diverse cascades in neurons and glia. Thus,
      AAV-mediated L1 overexpression appears to be a potent means to favourably modify
      the local environment in the injured spinal cord and promote regeneration. Our
      study demonstrates a clinically feasible approach of promising potential.

PMID- 17438017
TI  - Electrophysiological evidence that olfactory cell transplants improve function
      after spinal cord injury.
AB  - Transplants of cells obtained from the olfactory system are a potential treatment
      for spinal cord injury and a number of clinical trials are in progress. However,
      the extent to which transplants improve recovery of function remains unclear and
      there are contradictory reports on the extent to which they support axonal
      regeneration. Here, we have used anatomical and electrophysiological techniques
      to investigate the repair promoted by olfactory cell transplants after a dorsal
      column lesion. Since the use of olfactory cells of varying type and origin may
      contribute to the differing outcomes of previous studies, regeneration of dorsal
      column axons was compared following transplants of pure olfactory ensheathing
      cells from neonatal animals and mixed olfactory cells from both neonatal and
      adult rats. Two to three months after lesioning, numerous regenerating fibres
      could be seen in each type of transplant. However, tracing of ascending dorsal
      column fibres showed that few regenerated beyond the lesion, even when
      transplanted with mixed olfactory cells from the adult olfactory bulb which have
      previously been reported to support regeneration which bridges a lesion. Despite
      the absence of axonal regeneration across the injury site, olfactory cell
      transplants led to improved spinal cord function in sensory pathways investigated
      electrophysiologically. When cord dorsum potentials (CDPs), evoked by electrical
      stimulation of the L4/L5 dorsal roots, were recorded from the spinal cord above
      and below a lesion at the lumbar 3/4 level, CDPs recorded from transplanted
      animals were significantly larger than those recorded from lesioned controls. In
      addition, sensory evoked potentials recorded over the sensorimotor cortex were
      larger and detectable over a more extensive area in transplanted animals. These
      results provide direct evidence that transplants of olfactory cells preserve the
      function of circuitry in the region of the lesion site and of ascending pathways
      originating near the injury. These actions, rather than axonal regeneration, may
      help ameliorate the effects of spinal cord injury.

PMID- 17438018
TI  - Peri-infarct depolarizations lead to loss of perfusion in ischaemic gyrencephalic
      cerebral cortex.
AB  - In the light of accumulating evidence for the occurrence of spontaneous cortical
      spreading depression and peri-infarct depolarizations in the human brain injured
      by trauma or aneurysmal subarachnoid haemorrhage, we used DC electrode recording
      and laser speckle imaging to study the relationship between depolarization events
      and perfusion in the ischaemic, gyrencephalic brain. In 14 adult male cats
      anaesthetized with chloralose, one cerebral hemisphere was exposed and the middle
      cerebral artery occluded. Surface cortical perfusion in core and penumbral
      territories was imaged semiquantitatively at intervals of 13 s for 4 h. Cortical
      surface DC potential was recorded. Time interval between changes in DC potential
      and in perfusion was examined, and this comparison was repeated using
      microelectrodes for DC potential in five similar experiments in a second
      laboratory. Mean pre-occlusion perfusion was 11707 +/- 4581 units (equivalent to
      CBF (cerebral blood flow) approximately 40.5 +/- SD 14.4 ml/100 g/min), and fell
      on occlusion to 5318 +/- 2916 (CBF approximately 17.1 +/- 8.3), 5291 +/- 3407
      (CBF approximately 17.0 +/- 10.1), and 6711 +/- 3271 (CBF approximately 22.2 +/-
      9.6), quickly recovering to 8704 +/- 4581 (CBF approximately 29.5 +/- 14.4), 9741
      +/- 4499 (CBF approximately 33.3 +/- 14.1) and 10 314 +/- 3762 (CBF approximately
      35.4 +/- 11.4) on the core, intermediate and outer penumbral gyri, respectively.
      Mean perfusion later fell secondarily on core and intermediate gyri but, overall,
      was preserved on the outer (upper level of perfusion) gyrus during the period of
      observation. Pattern and severity of transient changes in perfusion associated
      with depolarization events varied with gyral location; falls in perfusion were
      sometimes profound and irreversible, and followed rather than preceded
      depolarization. In this model of occlusive stroke, reductions in perfusion linked
      to peri-infarct depolarization events contribute to secondary deterioration in
      penumbral areas. The findings suggest that such events play a central rather than
      a subsidiary role in cerebral infarction in the gyrencephalic brain.

PMID- 17438019
TI  - Abnormal folate metabolism in foetuses affected by neural tube defects.
AB  - Folic acid supplementation can prevent many cases of neural tube defects (NTDs),
      whereas suboptimal maternal folate status is a risk factor, suggesting that
      folate metabolism is a key determinant of susceptibility to NTDs. Despite
      extensive genetic analysis of folate cycle enzymes, and quantification of
      metabolites in maternal blood, neither the protective mechanism nor the
      relationship between maternal folate status and susceptibility are understood in
      most cases. In order to investigate potential abnormalities in folate metabolism
      in the embryo itself, we derived primary fibroblastic cell lines from foetuses
      affected by NTDs and subjected them to the dU suppression test, a sensitive
      metabolic test of folate metabolism. Significantly, a subset of NTD cases
      exhibited low scores in this test, indicative of abnormalities in folate cycling
      that may be causally linked to the defect. Susceptibility to NTDs may be
      increased by suppression of the methylation cycle, which is interlinked with the
      folate cycle. However, reduced efficacy in the dU suppression test was not
      associated with altered abundance of the methylation cycle intermediates, s
      adenosylmethionine and s-adenosylhomocysteine, suggesting that a methylation
      cycle defect is unlikely to be responsible for the observed abnormality of folate
      metabolism. Genotyping of samples for known polymorphisms in genes encoding
      folate-associated enzymes did not reveal any correlation between specific
      genotypes and the observed abnormalities in folate metabolism. These data suggest
      that as yet unrecognized genetic variants result in embryonic abnormalities of
      folate cycling that may be causally related to NTDs.

PMID- 17438020
TI  - Meningeal B-cell follicles in secondary progressive multiple sclerosis associate
      with early onset of disease and severe cortical pathology.
AB  - Intrathecal antibody production is a hallmark of multiple sclerosis and humoral
      immunity is thought to play an important role in the inflammatory response and
      development of demyelinated lesions. The presence of lymphoid follicle-like
      structures in the cerebral meninges of some multiple sclerosis patients indicates
      that B-cell maturation can be sustained locally within the CNS and contribute to
      the establishment of a compartmentalized humoral immune response. In this study
      we examined the distribution of ectopic B-cell follicles in multiple sclerosis
      cases with primary and secondary progressive clinical courses to determine their
      association with clinical and neuropathological features. A detailed
      immunohistochemical and morphometric analysis was performed on post-mortem brain
      tissue samples from 29 secondary progressive (SP) and 7 primary progressive (PP)
      multiple sclerosis cases. B-cell follicles were detected in the meninges entering
      the cerebral sulci of 41.4% of the SPMS cases, but not in PPMS cases. The SPMS
      cases with follicles significantly differed from those without with respect to a
      younger age at multiple sclerosis onset, irreversible disability and death and
      more pronounced demyelination, microglia activation and loss of neurites in the
      cerebral cortex. Cortical demyelination in these SPMS cases was also more severe
      than in PPMS cases. Notably, all meningeal B-cell follicles were found adjacent
      to large subpial cortical lesions, suggesting that soluble factors diffusing from
      these structures have a pathogenic role. These data support an immunopathogenetic
      mechanism whereby B-cell follicles developing in the multiple sclerosis meninges
      exacerbate the detrimental effects of humoral immunity with a subsequent major
      impact on the integrity of the cortical structures.

PMID- 17438021
TI  - Neural basis of category-specific semantic deficits for living things: evidence
      from semantic dementia, HSVE and a neural network model.
AB  - Studies of patients with semantic impairments following brain damage offer key
      insights into the cognitive and neural organization of semantic memory.
      Especially important in this regard are studies of category-specific semantic
      impairment. We report a direct comparison of semantic deficits in two groups
      suffering from different diseases: semantic dementia (SD) and herpes simplex
      virus encephalitis (HSVE). Although pathology in both disorders is centred on the
      anterior temporal lobes bilaterally, category-specific semantic impairment is
      rarely observed in SD yet commonly found in HSVE. Using a combination of
      neuropsychology and computational neuroscience, we tested the possibility that
      category-specific deficits for living things depend not solely upon the location
      of damage within the cortical semantic network but also critically upon the type
      of impairment. When the semantic representations within the model are degraded or
      'dimmed' then a generalized, global semantic impairment results (as found in SD)
      but when the representations are distorted then a category-specific pattern
      emerges (as per HSVE). Three novel predictions from this model were tested and
      confirmed, thereby adding weight to the hypothesis that both type and
      distribution of pathology can be critical in producing neuropsychological
      phenomena.

PMID- 17438022
TI  - The HlyU protein is a positive regulator of rtxA1, a gene responsible for
      cytotoxicity and virulence in the human pathogen Vibrio vulnificus.
AB  - Vibrio vulnificus is an opportunistic human pathogen that preferentially infects
      compromised iron-overloaded patients, causing a fatal primary septicemia with
      very rapid progress, resulting in a high mortality rate. In this study we
      determined that the HlyU protein, a virulence factor in V. vulnificus CMCP6, up
      regulates the expression of VV20479, a homologue of the Vibrio cholerae RTX
      (repeats in toxin) toxin gene that we named rtxA1. This gene is part of an operon
      together with two other open reading frames, VV20481 and VV20480, that encode two
      predicted proteins, a peptide chain release factor 1 and a hemolysin
      acyltransferase, respectively. A mutation in rtxA1 not only contributes to the
      loss of cytotoxic activity but also results in a decrease in virulence, whereas a
      deletion of VV20481 and VV20480 causes a slight decrease in virulence but with no
      effect in cytotoxicity. Activation of the expression of the rtxA1 operon by HlyU
      occurs at the transcription initiation level by binding of the HlyU protein to a
      region upstream of this operon.

PMID- 17438023
TI  - Role of motility and the flhDC Operon in Escherichia coli MG1655 colonization of
      the mouse intestine.
AB  - Previously, we reported that the mouse intestine selected mutants of Escherichia
      coli MG1655 that have improved colonizing ability (M. P. Leatham et al., Infect.
      Immun. 73:8039-8049, 2005). These mutants grew 10 to 20% faster than their parent
      in mouse cecal mucus in vitro and 15 to 30% faster on several sugars found in the
      mouse intestine. The mutants were nonmotile and had deletions of various lengths
      beginning immediately downstream of an IS1 element located within the regulatory
      region of the flhDC operon, which encodes the master regulator of flagellum
      biosynthesis, FlhD(4)C(2). Here we show that during intestinal colonization by
      wild-type E. coli strain MG1655, 45 to 50% of the cells became nonmotile by day 3
      after feeding of the strain to mice and between 80 and 90% of the cells were
      nonmotile by day 15 after feeding. Ten nonmotile mutants isolated from mice were
      sequenced, and all were found to have flhDC deletions of various lengths. Despite
      this strong selection, 10 to 20% of the E. coli MG1655 cells remained motile over
      a 15-day period, suggesting that there is an as-yet-undefined intestinal niche in
      which motility is an advantage. The deletions appear to be selected in the
      intestine for two reasons. First, genes unrelated to motility that are normally
      either directly or indirectly repressed by FlhD(4)C(2) but can contribute to
      maximum colonizing ability are released from repression. Second, energy normally
      used to synthesize flagella and turn the flagellar motor is redirected to growth.

PMID- 17438025
TI  - Identification of transferrin-binding domains in TbpB expressed by Neisseria
      gonorrhoeae.
AB  - The transferrin iron acquisition system of Neisseria gonorrhoeae is necessary for
      iron uptake from transferrin in the human host and requires the participation of
      two distinct proteins: TbpA and TbpB. TbpA is a TonB-dependent outer membrane
      transporter responsible for the transport of iron into the cell. TbpB is a lipid
      modified protein, for which a precise role in receptor function has not yet been
      elucidated. These receptor complex proteins show promise as vaccine candidates;
      therefore, it is important to identify surface-exposed regions of the proteins
      required for wild-type functions. In this study we examined TbpB, which has been
      reported to be surface exposed in its entirety; however, this hypothesis has
      never been tested experimentally. We placed the hemagglutinin (HA) epitope into
      TbpB with the dual purpose of examining the surface exposure of particular
      epitopes as well as their impact on receptor function. Nine insertion mutants
      were created, placing the epitope downstream of the signal peptidase II cleavage
      site. We report that the HA epitope is surface accessible in all mutants,
      indicating that the full-length TbpB is completely surface exposed. By expressing
      the TbpB-HA fusion proteins in N. gonorrhoeae, we were able to examine the impact
      of each insertion on the function of TbpB and the transferrin acquisition
      process. We propose that TbpB is comprised of two transferrin-binding-competent
      lobes, both of which are critical for efficient iron uptake from human
      transferrin.

PMID- 17438024
TI  - Heterogeneity in the activity of Mexican Helicobacter pylori strains in gastric
      epithelial cells and its association with diversity in the cagA gene.
AB  - Helicobacter pylori CagA is translocated into gastric epithelial cells by a type
      IV secretion system and interacts with the Src homology 2 phosphatase, altering
      cell morphology. Multiple EPIYA motifs in CagA are associated with increased
      activity in cells and with gastric cancer. The aim of this work was to study the
      heterogeneity in activity in cells of multiple H. pylori single colonies isolated
      from a single patient and its association with polymorphism in cagA. The presence
      of cagA, cagE, cagT, and cag10 was studied with 318 H. pylori isolates from the
      antra and corpora of 18 patients. AGS gastric epithelial cells were infected with
      75 isolates, and interleukin-8 (IL-8) secretion, cytoskeletal changes, CagA
      translocation, and tyrosine phosphorylation were measured. The cagA 3'-variable
      region was sequenced for 30 isolates to determine the number and types of EPIYA
      motifs. Isolates from an individual stomach were usually genetically related and
      had quantitatively similar phenotypic effects on cells (IL-8 induction and
      cytoskeletal changes). However, strains from different patients with similar CagA
      EPIYA motif patterns varied widely in these phenotypes. Among isolates with an
      EPIYA-ABC pattern, the phenotype was variable: IL-8 induction ranged from 200 to
      1,200 pg/ml, and morphological changes occurred in 20 to 70% of cells. In several
      cases, cagA sequence diversity appeared to explain the lack of CagA activity, as
      isolates with an EPIYA-ACC pattern or a modified B motif had reduced cell
      activity. cag pathogenicity island-positive H. pylori isolates displayed a high
      level of heterogeneity in the capacity to induce IL-8 secretion and morphological
      changes; an absent or modified B motif was associated with low activity.

PMID- 17438026
TI  - RyhB, an iron-responsive small RNA molecule, regulates Shigella dysenteriae
      virulence.
AB  - Regulation of bacterial gene expression by small RNA (sRNA) molecules is an
      increasingly recognized phenomenon but one that is not yet fully understood. We
      show that the sRNA RyhB suppresses several virulence-associated phenotypes of
      Shigella dysenteriae, a causative agent of bacillary dysentery in humans. The
      virulence genes repressed by S. dysenteriae RyhB include those encoding the type
      III secretion apparatus, its secreted effectors, and specific chaperones.
      Suppression of Shigella virulence occurs via RyhB-dependent repression of the
      transcriptional activator VirB, leading to reduced expression of genes within the
      VirB regulon. Efficient repression of virB is mediated by a single-stranded
      region of RyhB that is distinct from the region required for repression of
      Shigella sodB. Regulation of virB by RyhB implicates iron as an environmental
      factor contributing to the complex regulation of Shigella virulence determinants.

PMID- 17438028
TI  - The cytotoxic necrotizing factors from Yersinia pseudotuberculosis and from
      Escherichia coli bind to different cellular receptors but take the same route to
      the cytosol.
AB  - The cytotoxic necrotizing factors CNF1 and CNF2 produced by pathogenic
      Escherichia coli strains and CNF(Y) of Yersinia pseudotuberculosis constitutively
      activate small GTPases of the Rho family. They deamidate a glutamine (Gln63 in
      RhoA), which is crucial for GTP hydrolysis. CNF1 and CNF(Y) exhibit 61% identity
      on the amino acid level, with equal distribution over the whole molecule.
      Although the two toxins are homologous in the receptor binding domain, we show
      that they bind to different cellular receptors. CNF(Y) does not enter Caco-2 and
      CHO-K1 cells, which are responsive to CNF1. In contrast, HeLa, Hep-2, and HEK 293
      cells do respond to both toxins. Competition studies with catalytically inactive
      mutants of the toxins revealed that binding of CNF1 has no influence on the
      uptake of CNF(Y) into HeLa cells. In contrast, uptake of CNF1 is retarded after
      preincubation of HeLa cells with the catalytically inactive mutant of CNF(Y),
      suggesting that the toxin receptors overlap. Moreover, we compared the pathways
      of the toxins from receptor binding into the cytosol and showed that both toxins
      are taken up independent of the presence of clathrin or lipid rafts and are
      released into the cytosol from acidified endosomes.

PMID- 17438027
TI  - Expression and cellular localization of molecules of the gp82 family in
      Trypanosoma cruzi metacyclic trypomastigotes.
AB  - A member of the Trypanosoma cruzi gp82 family, expressed on metacyclic
      trypomastigote surface and identified by monoclonal antibody (MAb) 3F6, plays a
      key role in host cell invasion. Apart from the gp82 defined by MAb 3F6, no
      information is available on members of this protein family. From cDNA clones
      encoding gp82 proteins sharing 59.1% sequence identity, we produced the
      recombinant proteins J18 and C03, the former containing and the latter lacking
      the epitope for MAb 3F6. Polyclonal antibodies to J18 and C03 proteins were
      generated and used, along with MAb 3F6, to analyze the expression and cellular
      localization of gp82 family members in metacyclic forms of CL and G strains,
      which belong to highly divergent genetic groups. By two-dimensional gel
      electrophoresis and immunoblotting, molecules of 82 to 86 kDa, focusing at pH 4.6
      to 5.4, and molecules of 72 to 88 kDa, focusing at pH 4.9 to 5.7, were visualized
      in CL and G strains, respectively. Flow cytometry and microscopic analysis
      revealed in both strains similar expression of MAb 3F6-reactive gp82 in live and
      permeabilized parasites, indicating its surface localization. The reaction of
      live parasites of both strains with anti-J18 antibodies was weaker than with MAb
      3F6 and was increased by permeabilization. Anti-C03 antibodies bound
      predominantly to flagellar components in permeabilized G strain parasites, but in
      the CL strain the flagellum was not the preferential target for these antibodies.
      Host cell invasion of metacyclic forms was inhibited by J18 protein, as well as
      by MAb 3F6 and anti-J18 antibodies, but not by C03 protein or anti-C03
      antibodies.

PMID- 17438029
TI  - T cells are essential for bacterial clearance, and gamma interferon, tumor
      necrosis factor alpha, and B cells are crucial for disease development in
      Coxiella burnetii infection in mice.
AB  - Coxiella burnetii, the etiological agent of Q fever, has two phase variants.
      Phase I has a complete lipopolysaccharide (LPS), is highly virulent, and causes Q
      fever in humans and pathology in experimental animals. Phase II lacks an LPS O
      side chain, is avirulent, and does not grow well in immunocompetent animals. To
      understand the pathogenicity of Q fever, we investigated the roles of immune
      components in animals infected with Nine Mile phase I (NM I) or Nine Mile phase
      II (NM II) bacteria. Immunodeficient mice, including SCID mice (deficient in T
      and B cells), SCIDbg mice (deficient in T, B, and NK cells), nude mice (deficient
      in T cells), muMT mice (deficient in B cells), bg mice (deficient in NK cells),
      mice deficient in tumor necrosis factor alpha (TNF-alpha(-/-) mice), and mice
      deficient in gamma interferon (IFN-gamma(-/-) mice), were compared for their
      responses to infection. SCID, SCIDbg, nude, and IFN-gamma(-/-) mice showed high
      susceptibility to NM I, and TNF-alpha(-/-) mice showed modest susceptibility.
      Disease caused by NM I in SCID, SCIDbg, and nude mice progressed slowly, while
      disease in IFN-gamma(-/-) and TNF-alpha(-/-) mice advanced rapidly. B- and NK
      cell deficiencies did not enhance clinical disease development or alter bacterial
      clearance but did increase the severity of histopathological changes,
      particularly in the absence of B cells. Mice infected with NM II showed no
      apparent clinical disease, but T-cell-deficient mice had histopathological
      changes. These results suggest that T cells are critical for clearance of C.
      burnetii, either NM I or NM II, that IFN-gamma and TNF-alpha are essential for
      the early control of infection, and that B cells are important for the prevention
      of tissue damage.

PMID- 17438031
TI  - Memory CD4 T cells enhance primary CD8 T-cell responses.
AB  - CD4 T-cell help is required for optimal memory CD8 T-cell responses. We have
      found that engaging preexisting CD4 Th1, but not Th2, memory cells at the time of
      CD8 T-cell priming results in increased CD8 effector responses to both bacterial
      and viral pathogens. The enhanced responses are characterized by increased
      numbers of cytokine-producing, antigen-specific cells. These findings suggest
      that engaging endogenous memory Th1 cells may increase cellular responses in an
      immunotherapy or vaccination setting.

PMID- 17438030
TI  - Evaluation of the role of LcrV-Toll-like receptor 2-mediated immunomodulation in
      the virulence of Yersinia pestis.
AB  - Pathogenic members of the Yersinia genus require the translocator protein LcrV
      for proper function of the type III secretion apparatus, which is crucial for
      virulence. LcrV has also been reported to play an independent immunosuppressive
      role via the induction of interleukin-10 (IL-10) through stimulation of Toll-like
      receptor 2 (TLR2). To investigate the LcrV-TLR2 interaction in vitro, His-tagged
      recombinant LcrV (rLcrV) from Yersinia pestis was cloned and expressed in
      Escherichia coli and purified through Ni-nitrilotriacetic acid column
      chromatography. High concentrations (5 microg/ml) of rLcrV stimulated TLR2 in
      vitro. Fractionation of rLcrV preparations via gel filtration revealed that only
      a minor component consisting of high-molecular-weight multimers or aggregates has
      TLR2 stimulating activity. Dimer and tetramer forms of rLcrV, which constitute
      the bulk of the material, do not have this activity. To investigate the potential
      role of LcrV/TLR2 in plague pathogenesis, we infected wild-type and TLR2(-/-)
      mice with virulent Y. pestis. No discernible difference between the two mouse
      strains in severity of disease or kinetics of survival after subcutaneous
      challenge was observed. IL-6, tumor necrosis factor, and IL-10 levels from spleen
      homogenates; bacterial load; and the extent of inflammation observed in organs
      from mice infected intravenously were also indistinguishable in both mouse
      strains. Taken together, our data indicate that the most abundant molecular
      species of Y. pestis LcrV do not efficiently activate TLR2-signaling and that
      TLR2-mediated immunomodulation is unlikely to play a significant role in plague.

PMID- 17438032
TI  - Both complement- and fibrinogen-dependent mechanisms contribute to platelet
      aggregation mediated by Staphylococcus aureus clumping factor B.
AB  - Staphylococcus aureus can stimulate activation and aggregation of platelets,
      which are thought to be factors in the development of infective endocarditis.
      Previous studies have identified clumping factor A (ClfA) and fibronectin binding
      proteins A and B (FnBPA and FnBPB) as potent platelet aggregators. These proteins
      are able to stimulate rapid platelet aggregation by either a fibrinogen- or a
      fibronectin-dependent process which also requires antibodies specific to each
      protein. Slower aggregation has been seen in other systems where specific
      fibrinogen binding ligands are absent and platelet aggregation is mediated by
      complement and specific antibodies. Bacteria expressing ClfB aggregate platelets
      with a longer lag time than ClfA or FnBPA and FnBPB. In order to investigate
      whether ClfB causes platelet aggregation in a complement- or fibrinogen-dependent
      manner, a non-fibrinogen-binding mutant of ClfB (ClfB Q235A) was constructed.
      Lactococcus lactis expressing ClfB Q235A was able to stimulate platelet
      aggregation in platelet-rich plasma without a significant increase in lag time.
      The requirements for platelet aggregation were investigated using gel-filtered
      platelets. Fibrinogen and specific anti-ClfB antibodies were found to be
      sufficient to allow platelet aggregation mediated by the wild-type ClfB protein.
      It seems that ClfB causes platelet aggregation by a fibrinogen-dependent
      mechanism. The non-fibrinogen-binding ClfB mutant was unable to stimulate
      platelet aggregation under these conditions. However, bacteria expressing ClfB
      Q235A caused platelet aggregation in a complement-dependent manner which required
      specific anti-ClfB antibodies.

PMID- 17438033
TI  - Rapid escape of the dot/icm mutants of Legionella pneumophila into the cytosol of
      mammalian and protozoan cells.
AB  - The Legionella pneumophila-containing phagosome evades endocytic fusion and
      intercepts endoplasmic reticulum (ER)-to-Golgi vesicle traffic, which is believed
      to be mediated by the Dot/Icm type IV secretion system. Although phagosomes
      harboring dot/icm mutants are thought to mature through the endosomal-lysosomal
      pathway, colocalization studies with lysosomal markers have reported
      contradictory results. In addition, phagosomes harboring the dot/icm mutants do
      not interact with endocytosed materials, which is inconsistent with maturation of
      the phagosomes in the endosomal-lysosomal pathway. Using multiple strategies, we
      show that the dot/icm mutants defective in the Dot/Icm structural apparatus are
      unable to maintain the integrity of their phagosomes and escape into the
      cytoplasm within minutes of entry into various mammalian and protozoan cells in a
      process independent of the type II secretion system. In contrast, mutants
      defective in cytoplasmic chaperones of Dot/Icm effectors and rpoS, letA/S, and
      letE regulatory mutants are all localized within intact phagosomes. Importantly,
      non-dot/icm L. pneumophila mutants whose phagosomes acquire late endosomal
      lysosomal markers are all located within intact phagosomes. Using high-resolution
      electron microscopy, we show that phagosomes harboring the dot/icm transporter
      mutants do not fuse to lysosomes but are free in the cytoplasm. Inhibition of ER
      to-Golgi vesicle traffic by brefeldin A does not affect the integrity of the
      phagosomes harboring the parental strain of L. pneumophila. We conclude that the
      Dot/Icm transporter is involved in maintaining the integrity of the L.
      pneumophila phagosome, independent of interception of ER-to-Golgi vesicle
      traffic, which is a novel function of type IV secretion systems.

PMID- 17438034
TI  - Genome sequence of a clinical isolate of Campylobacter jejuni from Thailand.
AB  - Campylobacter jejuni CG8486, which belongs to the HS4 complex, was isolated from
      a patient with inflammatory diarrhea in Thailand. This strain caused a diarrheal
      disease in ferrets comparable to that caused by C. jejuni strain 81-176, but it
      was much less invasive for epithelial cells in vitro than 81-176. Complete genome
      sequencing of CG8486 revealed a 1.65-Mb genome that was very similar to the other
      two published genomes of clinical isolates of C. jejuni, the genomes of 81-176
      and NCTC 11168, with a limited number of CG8486-specific genes mapping outside
      the hypervariable carbohydrate biosynthesis loci. These data suggest that the
      genes required for induction of inflammatory diarrhea are among the genes shared
      by CG8486 and 81-176 but that either major changes in the carbohydrate loci
      and/or more subtle changes in other genes may modulate virulence.

PMID- 17438036
TI  - Inhibition of Enterococcus faecium adherence to collagen by antibodies against
      high-affinity binding subdomains of Acm.
AB  - Strains of Enterococcus faecium express a cell wall-anchored protein, Acm, which
      mediates adherence to collagen. Here, we (i) identify the minimal and high
      affinity binding subsegments of Acm and (ii) show that anti-Acm immunoglobulin Gs
      (IgGs) purified against these subsegments reduced E. faecium TX2535 strain
      collagen adherence up to 73 and 50%, respectively, significantly more than the
      total IgGs against the full-length Acm A domain (28%) (P < 0.0001). Blocking Acm
      adherence with functional subsegment-specific antibodies raises the possibility
      of their use as therapeutic or prophylactic agents.

PMID- 17438035
TI  - Virulence potential of Ehrlichia chaffeensis strains of distinct genome
      sequences.
AB  - Human monocytic ehrlichiosis, one of the most frequent life-threatening tick
      borne zoonoses, is caused by Ehrlichia chaffeensis that lacks endotoxin and
      peptidoglycan. While sequence polymorphisms in several genes in E. chaffeensis
      strains have been reported, global genomic divergence and biological differences
      among strains are unknown. The objectives of the present study were to compare
      the genome sequences of strains of E. chaffeensis and to examine the virulence
      potentials of the strains with defined genome sequences. Genomic DNA was
      extracted from purified E. chaffeensis strains Wakulla and Liberty, and
      comparative genome hybridization was performed using a densely tiled microarray
      of 147,027 chromosome positions of the E. chaffeensis strain Arkansas genome. The
      results revealed that 4,663 and 5,325 positions in the chromosomes of strains
      Wakulla and Liberty, respectively, were different from those in the chromosome of
      strain Arkansas, including three common major polymorphic chromosomal regions. Of
      various functional categories, the differences were most concentrated in genes
      predicted to encode cell envelope proteins. Of all the open reading frames
      (ORFs), 21 omp-1 (p28 gene) paralogs, nine genes encoding hypothetical proteins,
      two genes encoding ankyrin repeat proteins, and hemE contained the most
      differences. Several highly polymorphic ORFs were confirmed by sequencing. When
      the E. chaffeensis strains were inoculated into severe combined immunodeficiency
      mice, the order of the severity of clinical signs and the bacterial burden
      detected in mice was Wakulla > Liberty > Arkansas. Severe diffuse inflammation
      and granulomatous inflammation were evident in the livers of mice infected with
      strains Wakulla and Arkansas, respectively, but not in the livers of mice
      infected with strain Liberty. These results revealed distinct virulence
      phenotypes of E. chaffeensis strains with defined genome sequences.

PMID- 17438037
TI  - Assessment of the kinetics of Treponema pallidum dissemination into blood and
      tissues in experimental syphilis by real-time quantitative PCR.
AB  - Little is known about the size and kinetics of treponemal burdens in blood and
      tissues during acquired or experimental syphilitic infection. We used real-time
      quantitative PCR to measure Treponema pallidum DNA levels in rabbits infected
      intratesticularly with the prototype Nichols strain. At the outset, we performed
      a series of in vitro blood spiking experiments to determine the effect of blood
      processing procedures on the distribution of treponemes in various blood
      components. T. pallidum DNA levels in plasma and whole blood were approximately
      10-fold higher than those in serum and more than 200-fold greater than those in
      peripheral blood mononuclear cells (PBMCs). Ten rabbits were inoculated
      intratesticularly with doses of treponemes ranging from 4 x 10(7) to 2 x 10(8)
      organisms. In five rabbits, T. pallidum DNA levels were measured sequentially in
      serum, plasma, whole blood, and PBMCs until sacrifice at peak orchitis, at which
      time brain, kidney, liver, spleen, and testicles were harvested; blood and organs
      were also harvested at orchitis from the other five rabbits. T. pallidum DNA was
      detected in plasma within 24 h postinfection. Treponeme levels in whole blood and
      blood components increased significantly with the development of peak orchitis.
      Overall, levels in serum and PBMCs were lower than those in plasma and whole
      blood; this disparity was particularly marked at early time points. Significantly
      greater numbers of spirochetes were found in the spleen than in liver, kidney, or
      brain tissue at the time of sacrifice. Our findings highlight the remarkable
      capacity of T. pallidum to disseminate from the site of infection to blood and
      tissues, and they identify the spleen as a prime target for treponemal invasion.

PMID- 17438038
TI  - Invasion pathways and malaria severity in Kenyan Plasmodium falciparum clinical
      isolates.
AB  - The invasion of erythrocytes by Plasmodium falciparum occurs through multiple
      pathways that can be studied in vitro by examining the invasion of erythrocytes
      treated with enzymes such as neuraminidase, trypsin, and chymotrypsin. We have
      studied the invasion pathways used by 31 Kenyan P. falciparum isolates from
      children with uncomplicated or severe malaria. Six distinct invasion profiles
      were detected, out of eight possible profiles. The majority of isolates (23 of
      31) showed neuraminidase-resistant, trypsin-sensitive invasion, characteristic of
      the pathway mediated by an unknown parasite ligand and erythrocyte receptor "X."
      The neuraminidase-sensitive, trypsin-sensitive phenotype consistent with invasion
      mediated by the binding of parasite ligand erythrocyte binding antigen 175 to
      glycophorin A, the most common invasion profile in a previous study of Gambian
      field isolates, was seen in only 3 of 31 Kenyan isolates. No particular invasion
      profile was associated with severe P. falciparum malaria, and there was no
      significant difference in the levels of inhibition by the various enzyme
      treatments between isolates from children with severe malaria and those from
      children with uncomplicated malaria (P, >0.1 for all enzymes; Mann-Whitney U
      test). These results do not support the hypothesis that differences in invasion
      phenotypes play an important role in malaria virulence and indicate that
      considerable gaps remain in our knowledge of the molecular basis of invasion
      pathways in natural P. falciparum infections.

PMID- 17438039
TI  - A functional NADPH oxidase prevents caspase involvement in the clearance of
      phagocytic neutrophils.
AB  - Neutrophils play a prominent role in host defense. Phagocytosis of bacteria leads
      to the formation of an active NADPH oxidase complex that generates reactive
      oxygen species for bactericidal purposes. A critical step in the resolution of
      inflammation is the uptake of neutrophils by macrophages; however, there are
      conflicting reports on the mechanisms leading to the apoptosis of phagocytic
      neutrophils. The aim of this study was to clarify the role of effector caspases
      in these processes. Caspase activity was measured by DEVDase activity assays or
      immunofluorescence detection of active caspase-3. With normal human and wild-type
      murine neutrophils there was no caspase activation following phagocytosis of
      Staphylococcus aureus. However, caspase activity was observed in phagocytic
      neutrophils with a defective NADPH oxidase, including neutrophils isolated from X
      linked gp91(phox) knockout chronic granulomatous disease mice. These results
      indicate that a functional NADPH oxidase and the generation of oxidants in the
      neutrophil phagosome prevent the activation of the cytoplasmic caspase cascade.

PMID- 17438040
TI  - Identification of a Campylobacter jejuni protein that cross-reacts with cholera
      toxin.
AB  - The question of whether Campylobacter jejuni produces a cholera toxin-like toxin
      (CTLT) has been controversial. The objective of this study was to identify the
      factor that cross-reacts with CT from C. jejuni. Filtrates of C. jejuni grown in
      four different liquid media reported to promote CTLT production were tested by
      Chinese hamster ovary (CHO) cell elongation assay and for reactivity with CT
      antibody using GM1 ganglioside enzyme-linked immunosorbent assay (ELISA) and
      immunoblotting. Protein sequence was determined by matrix-assisted laser
      desorption ionization-time of flight (MALDI TOF-TOF). Filtrates from seven
      reference strains reported to produce CTLT and from 80 clinical strains were
      negative in the CHO cell assay, but those from three reference strains and 16
      clinical strains were positive by GM1 ELISA. All strains tested, including C.
      jejuni NCTC 11168, which does not contain a CT gene homologue, possessed a 53-kDa
      protein which reacted with CT antibody by immunoblotting. This band was
      identified as the major outer membrane protein, PorA, of C. jejuni. CT antibody
      reacted by immunoblotting with a recombinant PorA, but antibody to the
      recombinant PorA did not react with CT. Our results indicate that C. jejuni does
      not produce a functional CTLT, but the reactivity of PorA with CT antibody would
      lead to the erroneous conclusion that C. jejuni produces a functional CTLT.

PMID- 17438041
TI  - Solution structure and dynamics of DNA duplexes containing the universal base
      analogues 5-nitroindole and 5-nitroindole 3-carboxamide.
AB  - Universal bases hybridize with all other natural DNA or RNA bases, and have
      applications in PCR and sequencing. We have analysed by nuclear magnetic
      resonance spectroscopy the structure and dynamics of three DNA oligonucleotides
      containing the universal base analogues 5-nitroindole and 5-nitroindole-3
      carboxamide. In all systems studied, both the 5-nitroindole nucleotide and the
      opposing nucleotide adopt a standard anti conformation and are fully stacked
      within the DNA duplex. The 5-nitroindole bases do not base pair with the
      nucleotide opposite them, but intercalate between this base and an adjacent
      Watson-Crick pair. In spite of their smooth accommodation within the DNA double
      helix, the 5-nitroindole-containing duplexes exist as a dynamic mixture of two
      different stacking configurations exchanging fast on the chemical shift
      timescale. These configurations depend on the relative intercalating positions of
      the universal base and the opposing base, and their exchange implies nucleotide
      opening motions on the millisecond time range. The structure of these nitroindole
      containing duplexes explains the mechanism by which these artificial moieties
      behave as universal bases.

PMID- 17438042
TI  - Multicopy blaOXA-58 gene as a source of high-level resistance to carbapenems in
      Acinetobacter baumannii.
AB  - The mechanisms at the origin of heterogeneous carbapenem resistance levels
      observed among Acinetobacter baumannii isolates collected in 2005 in a large
      University Hospital of Rome, Italy, were investigated. These isolates were
      related and possessed similar plasmids carrying the carbapenem-hydrolyzing
      oxacillinase gene bla(OXA-58) but showed variable levels of resistance to
      carbapenems. Analysis of sequences surrounding the bla(OXA-58) gene showed
      genetic variability, with the presence in several isolates of multiple copies of
      the bla(OXA-58) gene; this extra copy number was likely related to an IS26
      mediated transposition or recombination process.

PMID- 17438043
TI  - Isoniazid bactericidal activity and resistance emergence: integrating
      pharmacodynamics and pharmacogenomics to predict efficacy in different ethnic
      populations.
AB  - Isoniazid, administered as part of combination antituberculosis therapy, is
      responsible for most of the early bactericidal activity (EBA) of the regimen.
      However, the emergence of Mycobacterium tuberculosis resistance to isoniazid is a
      major problem. We examined the relationship between isoniazid exposure and M.
      tuberculosis microbial kill, as well as the emergence of resistance, in our in
      vitro pharmacodynamic model of tuberculosis. Since single-nucleotide
      polymorphisms of the N-acetyltransferase-2 gene lead to two different clearances
      of isoniazid from serum in patients, we simulated the isoniazid concentration
      time profiles encountered in both slow and fast acetylators. Both microbial kill
      and the emergence of resistance during monotherapy were associated with the ratio
      of the area under the isoniazid concentration-time curve from 0 to 24 h (AUC(0
      24)) to the isoniazid MIC. The time in mutant selection window hypothesis was
      rejected. Next, we utilized the in vitro relationship between the isoniazid AUC(0
      24)/MIC ratio and microbial kill, the distributions of isoniazid clearance in
      populations with different percentages of slow and fast acetylators, and the
      distribution of isoniazid MICs for isonazid-susceptible M. tuberculosis clinical
      isolates in Monte Carlo simulations to calculate the EBA expected for
      approximately 10,000 patients treated with 300 mg of isoniazid. For those patient
      populations in which the proportion of fast acetylators and the isoniazid MICs
      were high, the average EBA of the standard dose was approximately 0.3 log(10)
      CFU/ml/day and was thus suboptimal. Our approach, which utilizes preclinical
      pharmacodynamics and the genetically determined multimodal distributions of serum
      clearances, is a preclinical tool that may be able to predict the EBAs of various
      doses of new antituberculosis drugs.

PMID- 17438044
TI  - Association between embB codon 306 mutations and drug resistance in Mycobacterium
      tuberculosis.
AB  - embB306 mutants were detected in both ethambutol (EMB)-resistant and EMB
      susceptible strains of Mycobacterium tuberculosis. Multidrug-resistant (MDR)
      strains had a higher proportion of embB306 mutants than non-MDR strains (odds
      ratio, 6.78; P < 0.001). The embB306 locus is a candidate marker for rapid
      detection of MDR and extremely drug resistant tuberculosis.

PMID- 17438045
TI  - Statistical methods for establishing quality control ranges for antibacterial
      agents in Clinical and Laboratory Standards Institute susceptibility testing.
AB  - Quality control (QC) ranges for antimicrobial agents against QC strains for both
      dilution and disk diffusion testing are currently set by the Clinical and
      Laboratory Standards Institute (CLSI), using data gathered in predefined
      structured multilaboratory studies, so-called tier 2 studies. The ranges are
      finally selected by the relevant CLSI subcommittee, based largely on visual
      inspection and a few simple rules. We have developed statistical methods for
      analyzing the data from tier 2 studies and applied them to QC strain
      antimicrobial agent combinations from 178 dilution testing data sets and 48 disk
      diffusion data sets, including a method for identifying possible outlier data
      from individual laboratories. The methods are based on the fact that dilution
      testing MIC data were log normally distributed and disk diffusion zone diameter
      data were normally distributed. For dilution testing, compared to QC ranges
      actually set by CLSI, calculated ranges were identical in 68% of cases, narrower
      in 7% of cases, and wider in 14% of cases. For disk diffusion testing, calculated
      ranges were identical to CLSI ranges in 33% of cases, narrower in 8% of cases,
      and 1 to 2 mm wider in 58% of cases. Possible outliers were detected in 8% of
      diffusion test data but none of the disk diffusion data. Application of
      statistical techniques to the analysis of QC tier 2 data and the setting of QC
      ranges is relatively simple to perform on spreadsheets, and the output enhances
      the current CLSI methods for setting of QC ranges.

PMID- 17438046
TI  - Relationship of blood level and susceptibility in voriconazole treatment of
      histoplasmosis.

PMID- 17438047
TI  - The L80I substitution in the reverse transcriptase domain of the hepatitis B
      virus polymerase is associated with lamivudine resistance and enhanced viral
      replication in vitro.
AB  - Long-term lamivudine (LMV) treatment of chronic hepatitis B almost inevitably
      engenders viral resistance. Mutations that result in the replacement of the
      methionine at position 204 of the deoxynucleoside triphosphate-binding site of
      the hepatitis B virus (HBV) reverse transcriptase (rt) by isoleucine, valine, or
      (rarely) serine (rtM204I/V/S) confer high-level resistance to LMV but reduce
      replication efficiency. The subsequent selection or coselection of secondary
      mutations that partially restore replication efficiency is common and may
      influence drug resistance. Genotyping has shown that LMV treatment can select for
      HBV rtL80V/I mutants, but their prevalence and phenotype have not been
      documented. Analysis of a large sequence database revealed that rtL80V/I occurred
      almost exclusively in association with LMV resistance, and 85% of these isolates
      encoded rtL80I. Coselection of rtL80V/I occurred in 46% of isolates in which LMV
      resistance was attributable to rtM204I but only 9% of those in which resistance
      was attributable to rtM204V. Moreover, rtL80V/I did not occur in HBV genotype A
      isolates but occurred at similar frequencies in genotype B, C, and D isolates. In
      vitro phenotyping showed that although the rtL80I mutant by itself replicated
      less efficiently and was hypersensitive to LMV compared to the replication
      efficiency and sensitivity of its wild-type parent, the presence of rtL80I
      enhanced the replication efficiency of rt204I/V mutants without significantly
      affecting LMV resistance. Molecular modeling revealed that rt80 does not interact
      directly with the enzyme's substrates. Collectively, these results suggest that
      coselection of rtL80V/I and rtM204I/V occurs because the former compensates for
      the loss of replication efficiency associated with the acquisition of LMV
      resistance, particularly in the case of rtM204I.

PMID- 17438048
TI  - In vitro susceptibility of Sporothrix schenckii to six antifungal agents
      determined using three different methods.
AB  - The in vitro susceptibility of Sporothrix schenckii to antifungal drugs has been
      determined with three different methods. Nineteen Peruvian clinical isolates of
      S. schenckii were tested against amphotericin B (AB), flucytosine (FC),
      fluconazole (FZ), itraconazole (IZ), voriconazole (VZ), and ketoconazole (KZ).
      Modified NCCLS M38-A, Sensititre YeastOne (SYO), and ATB Fungus 2 (ATBF2) methods
      were used to determine the MICs. ATCC isolates of Candida parapsilosis, Candida
      krusei, and Aspergillus flavus were used for quality control. Sporothrix inocula
      were prepared with the mycelial form growing on potato dextrose agar at 28 +/- 2
      degrees C. MICs of AB, FC, FZ, and IZ were determined with all three methods, VZ
      with M38-A and SYO, and KZ with only SYO. The three methods showed high MICs of
      FZ and FC (MIC(90) of 0.5 microg/ml), being homogeneously lower than those of IZ
      and KZ. The M38-A method showed a variable MIC range of VZ (4.0 to 16 microg/ml);
      the geometric mean (GM) was 9.3 mug/ml. The MIC range of AB was wide (0.06 to 16
      microg/ml), but the GM was 1.2 microg/ml, suggesting that the MIC is strain
      dependent. Agreement (two log(2) dilutions) between commercial techniques and the
      modified M38-A method was very high with FZ, IZ, and FC. In AB and VZ, the
      agreement was lower, being related to the antifungal concentrations of each
      method. The highest activity against S. schenckii was found with IZ and KZ. Lack
      of activity was observed with FZ, VZ, and FC. When AB is indicated for
      sporotrichosis, the susceptibility of the strain must be analyzed. Commercial
      quantitative antifungal methods have a limited usefulness in S. schenckii.

PMID- 17438049
TI  - Antiplasmodial activity of aryltetralone lignans from Holostylis reniformis.
AB  - Extracts from Holostylis reniformis were tested in vivo against Plasmodium
      berghei and in vitro against a chloroquine-resistant strain of Plasmodium
      falciparum. The hexane extract of the roots was the most active, causing 67%
      reduction of parasitemia in vivo. From this extract, six lignans, including a new
      (7'R,8S,8'S)-3',4'-methylenedioxy-4,5-dimethoxy-2,7'-cyclolignan-7-one, were
      isolated and tested in vitro against P. falciparum. The three most active lignans
      showed 50% inhibitor concentrations of < or =0.32 microM. An evaluation of
      minimum lethal dose (30%) values showed low toxicity for these lignans in a
      hepatic cell line (Hep G2A16). Therefore, these compounds are potential
      candidates for the development of antimalarial drugs.

PMID- 17438050
TI  - Biochemical characterization of PER-2 and genetic environment of blaPER-2.
AB  - PER-2 was the first detected and the second most prevalent extended-spectrum beta
      lactamase in clinical pathogens isolated in Argentina and was also reported only
      in other South American countries. Citrobacter freundii 33587 was isolated in
      1999 in Buenos Aires and was resistant to all tested beta-lactams except
      cephamycins and carbapenems. The strain produced both plasmid-borne TEM-1 and PER
      2 (pI 5.4), which could be transferred by conjugation. By PCR screening, thermal
      asymmetric interlaced PCR, and DNA sequencing, we detected an ISPa12/IS1387a
      insertion sequence upstream of bla(PER-2), previously reported as also being
      associated with bla(PER-1). The presence of similar structures upstream of
      bla(PER-1) and bla(PER-2) suggests a common origin and mobilization. Compared to
      bla(PER-1) genes, an additional putative promoter for bla(PER-2) was found. PER-2
      kinetic analysis showed its high hydrolysis efficiencies toward both CTX and CAZ
      (k(cat)/K(m), 0.76 and 0.43 microM(-1).s(-1), respectively).

PMID- 17438051
TI  - blaVIM-2-harboring integrons isolated in India, Russia, and the United States
      arise from an ancestral class 1 integron predating the formation of the 3'
      conserved sequence.
AB  - The metallo-beta-lactamase gene bla(VIM-2) was identified in a strain of
      Pseudomonas aeruginosa isolated in India. The integron encoding bla(VIM-2) was
      virtually identical to those recently found in the United States and Russia.
      These unusual structures are likely to have arisen from an ancestral integron
      predating the formation of the 3' conserved sequence.

PMID- 17438052
TI  - Evidence and possible consequences of the phosphorylation of nucleoside reverse
      transcriptase inhibitors in human red blood cells.
AB  - The intracellular metabolism of nucleoside reverse transcriptase inhibitors
      (NRTI) in mononuclear cells has been thoroughly studied, but that in red blood
      cells (RBC) has been disregarded. However, the phosphorylation of other analogous
      nucleosides (in particular, ribavirin) has been described previously. In this
      study, we investigated for the first time the phosphorylation of NRTI in human
      RBC. The presence of intracellular zidovudine (AZT) monophosphate, AZT
      triphosphate, lamivudine (3TC) triphosphate, and tenofovir (TFV) diphosphate, as
      well as endogenous dATP, dGTP, and dTTP, in RBC collected from human
      immunodeficiency virus-infected patients was examined. We observed evidence of a
      selective phosphorylation of 3TC, TFV, and endogenous purine deoxynucleosides to
      generate their triphosphate moieties. Conversely, no trace of AZT phosphate
      metabolites was found, and only faint dTTP signals were visible. A comparison of
      intracellular TFV diphosphate and 3TC triphosphate levels in RBC and peripheral
      blood mononuclear cells (PBMC) further highlighted the specificity of NRTI
      metabolism in each cell type. These findings raise the issue of RBC involvement
      in drug-drug interaction, drug pharmacokinetics, and drug-induced toxicity.
      Moreover, the typical preparation of PBMC samples by gradient density
      centrifugation does not prevent their contamination with RBC. We demonstrated
      that the presence of RBC within PBMC hampers an accurate determination of
      intracellular TFV diphosphate and dATP levels in clinical PBMC samples. Thus, we
      recommend removing RBC during PBMC preparation by using an ammonium chloride
      solution to enhance both the accuracy and the precision of intracellular drug
      monitoring.

PMID- 17438053
TI  - Transient loss of high-level mupirocin resistance in Staphylococcus aureus due to
      MupA polymorphism.
AB  - Spontaneous loss of MupA-mediated high-level mupirocin resistance was observed in
      Staphylococcus aureus, although the isolate gave a PCR-positive test result for
      mupA. Sequencing of the mupA gene identified a single base-pair deletion that
      resulted in a frameshift mutation and loss of functional protein. Reversion to
      the wild-type allele and restoration of high-level resistance occurred with high
      frequency (>10(-6)), indicating the transient nature of MupA polymorphism.

PMID- 17438054
TI  - Isoniazid induces its own resistance in nonreplicating Mycobacterium
      tuberculosis.
AB  - Isoniazid (INH) resistance is most frequent among drug-resistant Mycobacterium
      tuberculosis clinical isolates. This study was conducted to investigate whether
      INH could induce its own resistance. During INH susceptibility testing in BACTEC
      12B and MGIT 960 media, weekly subcultures were made from the drug-containing
      media into fresh medium without drug and susceptibility testing was performed.
      Rifampin (RIF) was used as a control drug. M. tuberculosis H37Rv and three
      clinical isolates were tested in this study. INH-resistant subcultures were
      analyzed for catalase activity, INH susceptibility, and mutations associated with
      INH resistance. With inoculum size (10(4) bacilli) smaller than a size that
      contains spontaneously INH-resistant mutants, INH was found to induce resistance
      to itself in INH-tolerant persisters but not to other drugs. The minimum time
      required for induction of INH resistance was 5 to 6 days. In contrast, RIF did
      not induce RIF resistance. Eight subcultures with INH-induced resistance were
      analyzed, and two had a MIC of 0.4 microg/ml INH and six had MICs of over 2
      microg/ml INH. Four of the eight subcultures with INH-induced resistance had lost
      catalase activity, with three having katG mutations. Despite being a powerful
      frontline tuberculosis drug, INH has the potential drawback of inducing its own
      stable genetic resistance in INH-tolerant persisters. This finding helps to
      explain the higher frequency and prevalence of INH-resistant isolates than
      isolates with resistance to other drugs in patients.

PMID- 17438055
TI  - Beta-lactam resistance in Haemophilus parasuis Is mediated by plasmid pB1000
      bearing blaROB-1.
AB  - beta-Lactam resistance in Haemophilus parasuis is an emerging phenomenon that has
      not yet been characterized from a molecular perspective. Clinical high-level beta
      lactam-resistant isolates from Spain bore a novel plasmid, pB1000, expressing a
      functionally active ROB-1 beta-lactamase. Pulsed-field gel electrophoresis was
      applied for the first time to H. parasuis and showed that beta-lactam resistance
      is due to clonal spread of a resistant strain, BB1018, bearing pB1000.

PMID- 17438056
TI  - Polyamine effects on antibiotic susceptibility in bacteria.
AB  - Biogenic polyamines (e.g., spermidine and spermine) are a group of essential
      polycationic compounds found in all living cells. The effects of spermine and
      spermidine on antibiotic susceptibility were examined with gram-negative
      Escherichia coli and Salmonella enterica serovar Typhimurium bacteria and
      clinical isolates of Pseudomonas aeruginosa and with gram-positive Staphylococcus
      aureus bacteria, including methicillin-resistant S. aureus (MRSA). Exogenous
      spermine exerted a dose-dependent inhibition effect on the growth of E. coli, S.
      enterica serovar Typhimurium, and S. aureus but not P. aeruginosa, as depicted by
      MIC and growth curve measurements. While the MICs of polymyxin and ciprofloxacin
      were in general increased by exogenous spermine and spermidine in P. aeruginosa,
      this adverse effect was not observed in enteric bacteria and S. aureus. It was
      found that spermine and spermidine can decrease the MICs of beta-lactam
      antibiotics in all strains as well as other types of antibiotics in a strain
      dependent manner. Significantly, the MICs of oxacillin for MRSA Mu50 and N315
      were decreased more than 200-fold in the presence of spermine, and this effect of
      spermine was retained when assessed in the presence of divalent ions (magnesium
      or calcium; 3 mM) or sodium chloride (150 mM). The effect of spermine on the
      sensitization of P. aeruginosa and MRSA to antibiotics was further demonstrated
      by population analysis and time-killing assays. The results of checkerboard
      assays with E. coli and S. aureus indicated a strong synergistic effect of
      spermine in combination with beta-lactams and chloramphenicol. The decreased MICs
      of beta-lactams implied that the possible blockage of outer membrane porins by
      exogenous spermine or spermidine did not play a crucial role in most cases. In
      contrast, only the MIC of imipenem against P. aeruginosa was increased by
      exogenous spermine and spermidine, and this resistance effect was abolished in a
      mutant strain devoid of the outer membrane porin OprD. In E. coli, the MICs of
      carbenicillin, chloramphenicol, and tetracycline were decreased in two acrA
      mutants devoid of a major efflux pump, AcrAB. However, retention of the spermine
      effect on antibiotic susceptibility in two acrA mutants of E. coli suggested that
      the AcrAB efflux pump was not the target for a synergistic effect by spermine and
      antibiotics and ruled out the hypothesis of spermine serving as an efflux pump
      inhibitor in this organism. In summary, this interesting finding of the effect of
      spermine on antibiotic susceptibility provides the basis for a new potential
      approach against drug-resistant pathogens by use of existing beta-lactam
      antibiotics.

PMID- 17438057
TI  - Time-kill and synergism studies of ceftobiprole against Enterococcus faecalis,
      including beta-lactamase-producing and vancomycin-resistant isolates.
AB  - Ceftobiprole (BAL9141) is an investigational cephalosporin with broad in vitro
      activity against gram-positive cocci, including enterococci. Ceftobiprole MICs
      were determined for 93 isolates of Enterococcus faecalis (including 16 beta
      lactamase [Bla] producers and 17 vancomycin-resistant isolates) by an agar
      dilution method following the Clinical and Laboratory Standards Institute
      recommendations. Ceftobiprole MICs were also determined with a high inoculum
      concentration (10(7) CFU/ml) for a subset of five Bla producers belonging to
      different previously characterized clones by a broth dilution method. Time-kill
      and synergism studies (with either streptomycin or gentamicin) were performed
      with two beta-lactamase-producing isolates (TX0630 and TX5070) and two vancomycin
      resistant isolates (TX2484 [VanB] and TX2784 [VanA]). The MICs of ceftobiprole
      for 50 and 90% of the isolates tested were 0.25 and 1 microg/ml, respectively.
      All Bla producers and vancomycin-resistant isolates were inhibited by
      concentrations of </=1 and </=4 microg/ml, respectively, at the standard inoculum
      concentration. Ceftobiprole MICs at a high inoculum concentration for a subset of
      five Bla(+) E. faecalis isolates were </=1 microg/ml. Bactericidal activity was
      observed against four isolates tested at concentrations as low as 1 microg/ml
      regardless of the production of beta-lactamase or vancomycin resistance. A
      combination of ceftobiprole (0.5 microg/ml) and streptomycin (25 microg/ml) was
      synergistic against Bla(+) TX0630 and TX5070. Ceftobiprole (0.5 microg/ml) plus
      gentamicin (10 microg/ml) was synergistic against VanB isolate TX2484 and showed
      enhanced killing, but not synergism, against TX2784 (VanA), despite the absence
      of high-level resistance to gentamicin. In conclusion, ceftobiprole exhibited
      good in vitro activity against E. faecalis, including Bla(+) and vancomycin
      resistant strains, and exhibited synergism with aminoglycosides against selected
      isolates.

PMID- 17438058
TI  - Prophylactic effect of dietary seaweed Fucoidan against enteral prion infection.
AB  - Dietary seaweed fucoidan delays the onset of disease of enterally infected mice
      with scrapie when given orally for 6 days after infection, but not when given
      before the infection. This effect was not modified at a tested fucoidan dose
      range and appeared to reach the maximum level at a concentration of 2.5% or less
      in feed. Daily uptake of fucoidan might be prophylactic against prion diseases
      caused by ingestion of prion-contaminated materials, although further evaluation
      of its pharmacology remains to be done.

PMID- 17438059
TI  - A novel Giardia lamblia nitroreductase, GlNR1, interacts with nitazoxanide and
      other thiazolides.
AB  - The nitrothiazole analogue nitazoxanide [NTZ; 2-acetolyloxy-N-(5-nitro-2
      thiazolyl)benzamide] represents the parent compound of a class of drugs referred
      to as thiazolides and exhibits a broad spectrum of activities against a wide
      variety of helminths, protozoa, and enteric bacteria infecting animals and
      humans. NTZ and other thiazolides are active against a wide range of other
      intracellular and extracellular protozoan parasites in vitro and in vivo, but
      their mode of action and respective subcellular target(s) have only recently been
      investigated. In order to identify potential targets of NTZ and other thiazolides
      in Giardia lamblia trophozoites, we have developed an affinity chromatography
      system using the deacetylated derivative of NTZ, tizoxanide (TIZ), as a ligand.
      Affinity chromatography on TIZ-agarose using cell extracts of G. lamblia
      trophozoites resulted in the isolation of an approximately 35-kDa polypeptide,
      which was identified by mass spectrometry as a nitroreductase (NR) homologue
      (EAA43030.1). NR was overexpressed as a six-histidine-tagged recombinant protein
      in Escherichia coli, purified, and then characterized using an assay for oxygen
      insensitive NRs with dinitrotoluene as a substrate. This demonstrated that the NR
      was functionally active, and the protein was designated GlNR1. In this assay
      system, NR activity was severely inhibited by NTZ and other thiazolides,
      demonstrating that the antigiardial activity of these drugs could be, at least
      partially, mediated through inhibition of GlNR1.

PMID- 17438060
TI  - Paradoxical effect of Echinocandins across Candida species in vitro: evidence for
      echinocandin-specific and candida species-related differences.
AB  - Paradoxical growth of some Candida isolates occurs at concentrations above the
      MIC for echinocandins. In 60 Candida bloodstream isolates from cancer patients
      (20 C. albicans isolates and 10 isolates each of C. parapsilosis, C. tropicalis,
      C. krusei, and C. glabrata), paradoxical growth was more frequent with
      caspofungin than micafungin or anidulafungin, was unrelated to MIC, and was
      strikingly absent in C. glabrata isolates.

PMID- 17438061
TI  - Sensitivity of monkey B virus (Cercopithecine herpesvirus 1) to antiviral drugs:
      role of thymidine kinase in antiviral activities of substrate analogs and
      acyclonucleosides.
AB  - Herpes B virus (B virus [BV]) is a macaque herpesvirus that is occasionally
      transmitted to humans where it can cause rapidly ascending encephalitis that is
      often fatal. To understand the low susceptibility of BV to the acyclonucleosides,
      we have cloned, expressed, and characterized the BV thymidine kinase (TK), an
      enzyme that is expected to "activate" nucleoside analogs. This enzyme is similar
      in sequence and properties to the TK of herpes simplex virus (HSV), i.e., it has
      a broad substrate range and low enantioselectivity and is sensitive to inhibitors
      of HSV TKs. The BV enzyme phosphorylates some modified nucleosides and
      acyclonucleosides and l enantiomers of thymidine and related antiherpetic
      analogs. However, the potent anti-HSV drugs acyclovir (ACV), ganciclovir (GCV),
      and 5-bromovinyldeoxyuridine were poorly or not phosphorylated by the BV enzyme
      under the experimental conditions. The antiviral activities of a number of
      marketed antiherpes drugs and experimental compounds were compared against BV
      strains and, for comparison, HSV type 1 (HSV-1) in Vero cell cultures. For most
      compounds tested, BV was found to be about as sensitive as HSV-1 was. However, BV
      was less sensitive to ACV and GCV than HSV-1 was. The abilities of thymidine
      analogs and acyclonucleosides to inhibit replication of BV in Vero cell culture
      were not always proportional to their substrate properties for BV TK. Our studies
      characterize BV TK for the first time and suggest new lead compounds, e.g., 5
      ethyldeoxyuridine and pencyclovir, which may be superior to ACV or GCV as
      treatment for this emerging infectious disease.

PMID- 17438062
TI  - First case of emergence of atovaquone resistance in Plasmodium falciparum during
      second-line atovaquone-proguanil treatment in South America.

PMID- 17438063
TI  - Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T
      cells that facilitate tumor development.
AB  - We previously reported (Bell, D., P. Chomarat, D. Broyles, G. Netto, G.M. Harb,
      S. Lebecque, J. Valladeau, J. Davoust, K.A. Palucka, and J. Banchereau. 1999. J.
      Exp. Med. 190: 1417-1426) that breast cancer tumors are infiltrated with mature
      dendritic cells (DCs), which cluster with CD4(+) T cells. We now show that CD4(+)
      T cells infiltrating breast cancer tumors secrete type 1 (interferon gamma) as
      well as high levels of type 2 (interleukin [IL] 4 and IL-13) cytokines.
      Immunofluorescence staining of tissue sections revealed intense IL-13 staining on
      breast cancer cells. The expression of phosphorylated signal transducer and
      activator of transcription 6 in breast cancer cells suggests that IL-13 actually
      delivers signals to cancer cells. To determine the link between breast cancer,
      DCs, and CD4(+) T cells, we implanted human breast cancer cell lines in nonobese
      diabetic/LtSz-scid/scid beta2 microglobulin-deficient mice engrafted with human
      CD34(+) hematopoietic progenitor cells and autologous T cells. There, CD4(+) T
      cells promote early tumor development. This is dependent on DCs and can be
      partially prevented by administration of IL-13 antagonists. Thus, breast cancer
      targets DCs to facilitate its development.

PMID- 17438066
TI  - Discovery of ligands for Nurr1 by combined use of NMR screening with different
      isotopic and spin-labeling strategies.
AB  - A comprehensive approach to target screening, hit validation, and binding site
      determination by nuclear magnetic resonance (NMR) spectroscopy is presented. NMR
      (19)F signal perturbation was used to screen a small compound library and
      identify candidate ligands to the target of interest. Ligand dissociation
      constants were measured using a pegylated form of the protein, which resulted in
      a 2-fold increase in the strength of the saturation transfer difference signal.
      The initial small-molecule hits were further optimized by combining a residue
      specific labeling strategy, to identify the specific sites of interaction with
      the protein, with a second site screening approach based on relaxation
      enhancement using a paramagnetic probe. The advantages of this combination
      strategy in the identification and optimization of weak binding chemical entities
      early in a program are illustrated with the discovery of a low micromolar ligand
      (K(d) = 20 microM) for Nurr1 and identification of the binding site location
      through residue-specific (15)N isotope labeling and derivatization of Cys
      residues with 2-mercaptoethanol-1-(13)C.

PMID- 17438064
TI  - Fetal gene defects precipitate platelet-mediated pregnancy failure in factor V
      Leiden mothers.
AB  - We describe a mouse model of fetal loss in factor V Leiden (FvL) mothers in which
      fetal loss is triggered when the maternal prothrombotic state coincides with
      fetal gene defects that reduce activation of the protein C anticoagulant pathway
      within the placenta. Fetal loss is caused by disruption of placental
      morphogenesis at the stage of labyrinth layer formation and occurs in the absence
      of overt placental thrombosis, infarction, or perfusion defects. Platelet
      depletion or elimination of protease-activated receptor 4 (Par4) from the mother
      allows normal placentation and prevents fetal loss. These findings establish a
      cause-effect relationship for the observed epidemiologic association between
      maternal FvL status and fetal loss and identify fetal gene defects as risk
      modifiers of pregnancy failure in prothrombotic mothers. Pregnancy failure is
      mediated by Par4-dependent activation of maternal platelets at the fetomaternal
      interface and likely involves a pathogenic pathway independent of occlusive
      thrombosis. Our results further demonstrate that the interaction of two given
      thrombosis risk factors produces markedly disparate consequences on disease
      manifestation (i.e., thrombosis or pregnancy loss), depending on the vascular bed
      in which this interaction occurs.

PMID- 17438065
TI  - A subset of dendritic cells induces CD4+ T cells to produce IFN-gamma by an IL-12
      independent but CD70-dependent mechanism in vivo.
AB  - Interferon (IFN)-gamma, a cytokine critical for resistance to infection and
      tumors, is produced by CD4(+) helper T lymphocytes after stimulation by cultured
      dendritic cells (DCs) that secrete a cofactor, interleukin (IL)-12. We have
      identified a major IL-12-independent pathway whereby DCs induce IFN-gamma
      secreting T helper (Th)1 CD4(+) T cells in vivo. This pathway requires the
      membrane-associated tumor necrosis family member CD70 and was identified by
      targeting the LACK antigen from Leishmania major within an antibody to CD205 (DEC
      205), an uptake receptor on a subset of DCs. Another major DC subset, targeted
      with 33D1 anti-DCIR2 antibody, also induced IFN-gamma in vivo but required IL-12,
      not CD70. Isolated CD205(+) DCs expressed cell surface CD70 when presenting
      antigen to T cell receptor transgenic T cells, and this distinction was
      independent of maturation stimuli. CD70 was also essential for CD205(+) DC
      function in vivo. Detection of the IL-12-independent IFN-gamma pathway was
      obscured with nontargeted LACK, which was presented by both DC subsets. This in
      situ analysis points to CD70 as a decision maker for Th1 differentiation by
      CD205(+) DCs, even in Th2-prone BALB/c animals and potentially in vaccine design.
      The results indicate that two DC subsets have innate propensities to
      differentially affect the Th1/Th2 balance in vivo and by distinct mechanisms.

PMID- 17438067
TI  - "Plate cherry picking": a novel semi-sequential screening paradigm for cheaper,
      faster, information-rich compound selection.
AB  - This work describes a novel semi-sequential technique for in silico enhancement
      of high-throughput screening (HTS) experiments now employed at Novartis. It is
      used in situations in which the size of the screen is limited by the readout
      (e.g., high-content screens) or the amount of reagents or tools (proteins or
      cells) available. By performing computational chemical diversity selection on a
      per plate basis (instead of a per compound basis), 25% of the 1,000,000-compound
      screening was optimized for general initial HTS. Statistical models are then
      generated from target-specific primary results (percentage inhibition data) to
      drive the cherry picking and testing from the entire collection. Using
      retrospective analysis of 11 HTS campaigns, the authors show that this method
      would have captured on average two thirds of the active compounds (IC(50) < 10
      microM) and three fourths of the active Murcko scaffolds while decreasing
      screening expenditure by nearly 75%. This result is true for a wide variety of
      targets, including G-protein-coupled receptors, chemokine receptors, kinases,
      metalloproteinases, pathway screens, and protein-protein interactions. Unlike
      time-consuming "classic" sequential approaches that require multiple iterations
      of cherry picking, testing, and building statistical models, here individual
      compounds are cherry picked just once, based directly on primary screening data.
      Strikingly, the authors demonstrate that models built from primary data are as
      robust as models built from IC(50) data. This is true for all HTS campaigns
      analyzed, which represent a wide variety of target classes and assay types.

PMID- 17438068
TI  - Expression of human nuclear receptors in plants for the discovery of plant
      derived ligands.
AB  - Plants have the potential to produce a wide array of secondary metabolites that
      have utility as drugs to treat human diseases. To tap this potential, functional
      human nuclear receptors have been expressed in plants to create in planta
      screening assays as a tool to discover natural product ligands. Assays have been
      designed and validated using 3 nuclear receptors: the estrogen receptor (ER), the
      androgen receptor (AR), and the heterodimeric retinoid X receptor-alpha plus
      thyroid hormone receptor-beta (RXRA/THRB). Nuclear receptor-reporter constructs
      have been expressed in plants to detect the presence of natural ligands that are
      produced de novo in several plant species during different stages of development,
      in various tissues, and in response to different stress elicitors. Screening
      experiments with ER, AR, and RXRA/THRB have been conducted, leading to the
      identification of plant sources of natural product ligands of human nuclear
      receptors. This in planta screen has led to the identification of previously
      unreported ER ligands, providing evidence of the complementary value of this
      approach to current in vitro high-throughput screening assays.

PMID- 17438069
TI  - A simple, no-wash cell adhesion-based high-throughput assay for the discovery of
      small-molecule regulators of the integrin CD11b/CD18.
AB  - The leukocyte-specific integrin CD11b/CD18 plays a key role in the biological
      function of these cells and represents a validated therapeutic target for
      inflammatory diseases. Currently, the low affinity interaction between CD11b/CD18
      integrin and its respective ligand poses a challenge in the development of cell
      based adhesion assays for the high-throughput screening (HTS) environment. Here
      the authors describe a simple cell-based adhesion assay that can be readily used
      for HTS for the discovery of functional regulators of CD11b/CD18. The assay
      consistently produces acceptable Z' values (> 0.5) for HTS. After testing the
      assay using 2 established blocking antibodies as reference biologicals, the
      authors performed a proof-of-concept primary screen using a library of 6612
      compounds and identified both agonist and antagonist hits.

PMID- 17438070
TI  - Enhancing recombinant protein quality and yield by protein stability profiling.
AB  - The reliable production of large amounts of stable, high-quality proteins is a
      major challenge facing pharmaceutical protein biochemists, necessary for
      fulfilling demands from structural biology, for high-throughput screening, and
      for assay purposes throughout early discovery. One strategy for bypassing
      purification challenges in problematic systems is to engineer multiple forms of a
      particular protein to optimize expression, purification, and stability, often
      resulting in a nonphysiological sub-domain. An alternative strategy is to alter
      process conditions to maximize wild-type construct stability, based on a specific
      protein stability profile (PSP). ThermoFluor, a miniaturized 384-well thermal
      stability assay, has been implemented as a means of monitoring solution-dependent
      changes in protein stability, complementing the protein engineering and
      purification processes. A systematic analysis of pH, buffer or salt identity and
      concentration, biological metals, surfactants, and common excipients in terms of
      an effect on protein stability rapidly identifies conditions that might be used
      (or avoided) during protein production. Two PSPs are presented for the kinase
      catalytic domains of Akt-3 and cFMS, in which information derived from a
      ThermoFluor PSP led to an altered purification strategy, improving the yield and
      quality of the protein using the primary sequences of the catalytic domains.

PMID- 17438071
TI  - High-throughput screening for norepinephrine transporter inhibitors using the
      FLIPRTetra.
AB  - Monoamine transporters regulate the concentration of neurotransmitters in the
      synapse following neurotransmission and are very important drug targets in the
      pharmaceutical industry. Because of the labor-intensive nature of functional
      uptake assays using radioactive substrates, high-throughput screening for
      monoamine transporter inhibitors has been limited to radioligand binding assays.
      In this article, the authors describe the development of a 384-well, high
      throughput functional screening assay for norepinephrine transporter inhibitors
      using the FLIPR(Tetra) and a recently identified fluorescent substrate, 4-(4
      dimethylaminostyryl)- N-methyl-pyridinium (ASP(+)).

PMID- 17438072
TI  - The UNC-45 chaperone mediates sarcomere assembly through myosin degradation in
      Caenorhabditis elegans.
AB  - Myosin motors are central to diverse cellular processes in eukaryotes. Homologues
      of the myosin chaperone UNC-45 have been implicated in the assembly and function
      of myosin-containing structures in organisms from fungi to humans. In muscle, the
      assembly of sarcomeric myosin is regulated to produce stable, uniform thick
      filaments. Loss-of-function mutations in Caenorhabditis elegans UNC-45 lead to
      decreased muscle myosin accumulation and defective thick filament assembly,
      resulting in paralyzed animals. We report that transgenic worms overexpressing
      UNC-45 also display defects in myosin assembly, with decreased myosin content and
      a mild paralysis phenotype. We find that the reduced myosin accumulation is the
      result of degradation through the ubiquitin/proteasome system. Partial proteasome
      inhibition is able to restore myosin protein and worm motility to nearly wild
      type levels. These findings suggest a mechanism in which UNC-45-related proteins
      may contribute to the degradation of myosin in conditions such as heart failure
      and muscle wasting.

PMID- 17438073
TI  - Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand
      breaks.
AB  - The DNA-dependent protein kinase catalytic subunit (DNA-PK(CS)) plays an
      important role during the repair of DNA double-strand breaks (DSBs). It is
      recruited to DNA ends in the early stages of the nonhomologous end-joining (NHEJ)
      process, which mediates DSB repair. To study DNA-PK(CS) recruitment in vivo, we
      used a laser system to introduce DSBs in a specified region of the cell nucleus.
      We show that DNA-PK(CS) accumulates at DSB sites in a Ku80-dependent manner, and
      that neither the kinase activity nor the phosphorylation status of DNA-PK(CS)
      influences its initial accumulation. However, impairment of both of these
      functions results in deficient DSB repair and the maintained presence of DNA
      PK(CS) at unrepaired DSBs. The use of photobleaching techniques allowed us to
      determine that the kinase activity and phosphorylation status of DNA-PK(CS)
      influence the stability of its binding to DNA ends. We suggest a model in which
      DNA-PK(CS) phosphorylation/autophosphorylation facilitates NHEJ by destabilizing
      the interaction of DNA-PK(CS) with the DNA ends.

PMID- 17438074
TI  - Three-dimensional structures of the flagellar dynein-microtubule complex by
      cryoelectron microscopy.
AB  - The outer dynein arms (ODAs) of the flagellar axoneme generate forces needed for
      flagellar beating. Elucidation of the mechanisms underlying the chemomechanical
      energy conversion by the dynein arms and their orchestrated movement in
      cilia/flagella is of great importance, but the nucleotide-dependent three
      dimensional (3D) movement of dynein has not yet been observed. In this study, we
      establish a new method for reconstructing the 3D structure of the in vitro
      reconstituted ODA-microtubule complex and visualize nucleotide-dependent
      conformational changes using cryoelectron microscopy and image analysis. As the
      complex went from the rigor state to the relaxed state, the head domain of the
      beta heavy chain shifted by 3.7 nm toward the B tubule and inclined 44 degrees
      inwards. These observations suggest that there is a mechanism that converts head
      movement into the axonemal sliding motion.

PMID- 17438075
TI  - In macrophages, HIV-1 assembles into an intracellular plasma membrane domain
      containing the tetraspanins CD81, CD9, and CD53.
AB  - In macrophages, HIV-1 has been shown to bud into intracellular structures that
      contain the late endosome marker CD63. We show that these organelles are not
      endosomes, but an internally sequestered plasma membrane domain. Using
      immunofluorescence microscopy and immunoelectron microscopy, we find that HIV-1
      buds into a compartment that contains the tetraspanins CD81, CD9, and CD53. On
      uninfected macrophages, these proteins are seen at the cell surface and in
      intracellular vacuole-like structures with a complex content of vesicles and
      interconnected membranes that lack endosome markers, including CD63.
      Significantly, these structures are accessible to small tracers (horseradish
      peroxidase or ruthenium red) applied to cells at 4 degrees C, indicating that
      they are connected to the cell surface. HIV assembles on, and accumulates within,
      these intracellular compartments. Furthermore, CD63 is recruited to the virus
      containing structures and incorporated into virions. These results indicate that,
      in macrophages, HIV-1 exploits a previously undescribed intracellular plasma
      membrane domain to assemble infectious particles.

PMID- 17438076
TI  - Early endosomes associated with dynamic F-actin structures are required for late
      trafficking of H. pylori VacA toxin.
AB  - Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are endocytosed by a
      clathrin- independent pathway into vesicles named GPI-AP-enriched early endosomal
      compartments (GEECs). We recently showed that the vacuolating toxin VacA secreted
      by Helicobacter pylori is endocytosed into the GEECs (Gauthier, N.C., P. Monzo,
      V. Kaddai, A. Doye, V. Ricci, and P. Boquet. 2005. Mol. Biol. Cell. 16:4852
      4866). Unlike GPI-APs that are mostly recycled back to the plasma membrane, VacA
      reaches early endosomes (EEs) and then late endosomes (LEs), where vacuolation
      occurs. In this study, we used VacA to study the trafficking pathway between
      GEECs and LEs. We found that VacA routing from GEECs to LEs required polymerized
      actin. During this trafficking, VacA was transferred from GEECs to EEs associated
      with polymerized actin structures. The CD2-associated protein (CD2AP), a docking
      protein implicated in intracellular trafficking, bridged the filamentous actin (F
      actin) structures with EEs containing VacA. CD2AP regulated those F-actin
      structures and was required to transfer VacA from GEECs to LEs. These results
      demonstrate that sorting from GEECs to LEs requires dynamic F-actin structures on
      EEs.

PMID- 17438077
TI  - A signal from inside the peroxisome initiates its division by promoting the
      remodeling of the peroxisomal membrane.
AB  - We define the dynamics of spatial and temporal reorganization of the team of
      proteins and lipids serving peroxisome division. The peroxisome becomes competent
      for division only after it acquires the complete set of matrix proteins involved
      in lipid metabolism. Overloading the peroxisome with matrix proteins promotes the
      relocation of acyl-CoA oxidase (Aox), an enzyme of fatty acid beta-oxidation,
      from the matrix to the membrane. The binding of Aox to Pex16p, a membrane
      associated peroxin required for peroxisome biogenesis, initiates the biosynthesis
      of phosphatidic acid and diacylglycerol (DAG) in the membrane. The formation of
      these two lipids and the subsequent transbilayer movement of DAG initiate the
      assembly of a complex between the peroxins Pex10p and Pex19p, the dynamin-like
      GTPase Vps1p, and several actin cytoskeletal proteins on the peroxisomal surface.
      This protein team promotes membrane fission, thereby executing the terminal step
      of peroxisome division.

PMID- 17438078
TI  - Sending proteins to dense core secretory granules: still a lot to sort out.
AB  - The intracellular sorting of peptide hormone precursors to the dense core
      secretory granules (DCSGs) is essential for their bioactivation. Despite the
      fundamental importance of this cellular process, the nature of the sorting
      signals for entry of proteins into DCSGs remains a source of vigorous debate.
      This review highlights recent discoveries that are consistent with a model in
      which several protein domains, acting in a cell-specific fashion and at different
      steps in the sorting process, act in concert to regulate the entry of proteins
      into DCSGs.

PMID- 17438079
TI  - Identification of a novel functional specificity signal within the GPI anchor
      signal sequence of carcinoembryonic antigen.
AB  - Exchanging the glycophosphatidylinositol (GPI) anchor signal sequence of neural
      cell adhesion molecule (NCAM) for the signal sequence of carcinoembryonic antigen
      (CEA) generates a mature protein with NCAM external domains but CEA-like
      tumorigenic activity. We hypothesized that this resulted from the presence of a
      functional specificity signal within this sequence and generated CEA/NCAM
      chimeras to identify this signal. Replacing the residues (GLSAG) 6-10 amino acids
      downstream of the CEA anchor addition site with the corresponding NCAM residues
      resulted in GPI-anchored proteins lacking the CEA-like biological functions of
      integrin modulation and differentiation blockage. Transferring this region from
      CEA into NCAM in conjunction with the upstream proline (PGLSAG) was sufficient to
      specify the addition of the CEA anchor. Therefore, this study identifies a novel
      specificity signal consisting of six amino acids located within the GPI anchor
      attachment signal, which is necessary and sufficient to specify the addition of a
      particular functional GPI anchor and, thereby, the ultimate function of the
      mature protein.

PMID- 17438080
TI  - Dyssomnias and parasomnias in early childhood.
AB  - OBJECTIVES: Our aim for this study was to determine the prevalence of dyssomnias
      and various parasomnias in early childhood and to describe their temporal
      evolution, gender differences, and correlates. METHODS: This research is part of
      a longitudinal study of child development. A randomized, 3-level, stratified
      survey design was used to study a representative sample of infants who were born
      in 1997-1998 in the province of Quebec (Canada). When the children were 2.5 years
      of age, 1997 families agreed to be interviewed. The presence of dyssomnias or
      parasomnias was obtained from a self-administered questionnaire that was
      completed by the mother at each round of measures. RESULTS: The percentage of
      children with frequent night wakings decreased steadily from 36.3% at age 2.5 to
      13.2% at age 6. Similarly, the percentage of children who had difficulty falling
      asleep at night decreased significantly from 16.0% at ages 3.5 and 4 to 10% at
      age 5 and to 7.4% at age 6. The overall prevalence of each parasomnia for the
      period studied was as follows: somnambulism, 14.5%; sleep terrors, 39.8%;
      somniloquy, 84.4%; enuresis, 25.0%; bruxism, 45.6%; and rhythmic movements, 9.2%.
      Persistent somnambulism at age 6 was significantly correlated with sleep terrors
      and somniloquy. Persistent sleep terrors at age 6 were also correlated with
      somniloquy. Finally, persistent sleep terrors at age 6 were correlated with
      frequent night wakings. Separation anxiety was associated with persistent night
      wakings and with somnambulism, bruxism, sleep terrors, and somniloquy.
      CONCLUSIONS: There is a high prevalence of night wakings and sleep-onset
      difficulties in preschool children. Parasomnias are highly prevalent in early
      childhood and are associated with separation anxiety. However, they have little
      impact on sleep duration.

PMID- 17438081
TI  - Diagnosis of common variable immunodeficiency in a patient with primary ciliary
      dyskinesia.
AB  - In this case report we describe the first account in the literature of a patient
      with primary ciliary dyskinesia and common variable immunodeficiency. A 17-year
      old boy with previously diagnosed Kartagener syndrome and stable lung disease
      developed a deteriorating clinical course that prompted the search for a
      secondary diagnosis. Although both of these rare conditions can result in similar
      lung pathology, they require different management strategies, which illustrates
      the need to consider associated diagnoses in complicated clinical situations.

PMID- 17438082
TI  - Brain abnormalities in patients with hyperimmunoglobulin E syndrome.
AB  - OBJECTIVES: Hyperimmunoglobulin E syndrome is a multisystem disorder with
      abnormalities of the immunologic, connective tissue, and skeletal tissue systems.
      Central nervous system abnormalities have not been considered a feature of
      hyperimmunoglobulin E syndrome. We aimed to determine whether central nervous
      system abnormalities detected on brain MRI exist in hyperimmunoglobulin E
      syndrome and to characterize any identified abnormalities. PATIENTS AND METHODS:
      Fifty patients aged from 3 to 52 years (mean: 24 years) with established
      diagnoses of hyperimmunoglobulin E syndrome had MRI of the brain as part of an
      hyperimmunoglobulin E syndrome natural history protocol. Abnormalities were
      described, measured, counted, and mapped. Patient charts were reviewed for
      neurologic findings and blood pressure measurements. RESULTS: Focal brain lesions
      exhibiting high signal intensities on flow-attenuated inversion recovery and on
      T2-weighted techniques were found in 35 of the 50 patients. The focal
      hyperintensities were predominantly in the white matter of the cerebral
      hemispheres, and the number ranged from 2 to >50. The hyperintensities occurred
      more frequently in adults than in children, and no association with elevated
      blood pressure was found. Five patients had lacunar infarctions. Chiari type 1
      malformations were found in 9 of 50 patients. Two patients had infectious
      complications presenting on MRI as cerebritis in 1 patient and as a hemorrhagic
      infarct in the other; both were found on autopsy to be fungal. Neurologic
      abnormalities were present in 1 patient with a lacunar infarction, the 2 patients
      with infectious complications, and in 1 patient with a subarachnoid hemorrhage
      secondary to a berry aneurysm. CONCLUSIONS: Central nervous system abnormalities
      are common in hyperimmunoglobulin E syndrome. Focal T2 hyperintensities, not
      appreciated previously, represent a prominent feature of this rare disease that
      may assist in diagnosis. The etiology and clinical implications of these
      abnormalities remain to be investigated.

PMID- 17438083
TI  - Remission and relapse of Crohn's disease following autologous haematopoietic stem
      cell transplantation for non-Hodgkin's lymphoma.

PMID- 17438084
TI  - Induction and role of regulatory CD4+CD25+ T cells in tolerance to the transgene
      product following hepatic in vivo gene transfer.
AB  - Gene replacement therapy is complicated by the risk of an immune response against
      the therapeutic transgene product, which in part is determined by the route of
      vector administration. Our previous studies demonstrated induction of immune
      tolerance to coagulation factor IX (FIX) by hepatic adeno-associated viral (AAV)
      gene transfer. Using a regulatory T-cell (T(reg))-deficient model (Rag-2(-/-)
      mice transgenic for ovalbumin-specific T-cell receptor DO11.10), we provide first
      definitive evidence for induction of transgene product-specific CD4(+)CD25(+)
      T(regs) by in vivo gene transfer. Hepatic gene transfer-induced T(regs) express
      FoxP3, GITR, and CTLA4, and suppress CD4(+)CD25(-) T cells. T(regs) are detected
      as early as 2 weeks after gene transfer, and increase in frequency in thymus and
      secondary lymphoid organs during the following 2 months. Similarly, adoptive
      lymphocyte transfers from mice tolerized to human FIX by hepatic AAV gene
      transfer indicate induction of CD4(+)CD25(+)GITR(+) that suppresses antibody
      formation to FIX. Moreover, in vivo depletion of CD4(+)CD25(+) T(regs) leads to
      antibody formation to the FIX transgene product after hepatic gene transfer,
      which strongly suggests that these regulatory cells are required for tolerance
      induction. Our study reveals a crucial role of CD4(+)CD25(+) T(regs) in
      preventing immune responses to the transgene product in gene transfer.

PMID- 17438085
TI  - Galectin-1 mediated suppression of Epstein-Barr virus specific T-cell immunity in
      classic Hodgkin lymphoma.
AB  - In Hodgkin lymphoma (HL), the malignant Hodgkin Reed-Sternberg cells interact
      with the host microenvironment to create an immunosuppressive network that
      protects the lymphoma from immune attack. These mechanisms are not fully
      understood. We examined the role of the immunomodulatory protein galectin-1 (Gal
      1) on Epstein-Barr virus-specific CD8(+) T cell responses in HL. Initial studies
      indicated Gal-1 expression in all in vitro established Hodgkin Reed-Sternberg
      cell lines. In situ analysis revealed Gal-1 expression in 26 of 42 classic HL,
      whereas Gal-1 was uniformly negative in nodular lymphocyte predominant HL. Gal
      1(hi) expression was associated with male gender, older patients, reduced CD8(+)
      T cell infiltration at the tumor site, and most importantly, an impaired latent
      membrane protein 1 and 2-specific CD8(+) T-cell responses. In vitro exposure to
      recombinant Gal-1 inhibited proliferation and interferon-gamma expression by
      Epstein-Barr virus-specific T cells. These observations provide an important link
      between the Gal-1-mediated immunomodulatory networks and loss of antigen-specific
      T-cell function in classic HL.

PMID- 17438086
TI  - Phase II cancer trials: out of control?

PMID- 17438087
TI  - The use of epigenetic biomarkers for preclinical detection of hepatocellular
      carcinoma: potential for noninvasive screening of high-risk populations.

PMID- 17438088
TI  - Targeting TRAIL agonistic receptors for cancer therapy.
AB  - Based on preclinical studies demonstrating that tumor necrosis factor-related
      apoptosis-inducing ligand (TRAIL) exerts a potent and cancer cell-specific
      proapoptotic activity, recombinant TRAIL as well as agonistic anti-TRAIL-R1 and
      anti-TRAIL-R2 antibodies recently entered clinical trials. Additionally, gene
      therapy approaches using TRAIL-encoding adenovirus (Ad-TRAIL) are currently being
      developed to overcome the limitations inherent to TRAIL receptor targeting, i.e.,
      pharmacokinetic of soluble TRAIL, pattern of receptor expression, and tumor cell
      resistance. To optimize gene therapy approaches, CD34+ cells transduced with Ad
      TRAIL (CD34-TRAIL+) have been investigated as cellular vehicles for TRAIL
      delivery. Transduced cells exhibit a potent tumor killing activity on a variety
      of tumor cell types both in vitro and in vivo and are also cytotoxic against
      tumor cells resistant to soluble TRAIL. Studies in tumor-bearing nonobese
      diabetic/severe combined immunodeficient mice suggest that the antitumor effect
      of CD34-TRAIL+ cells is mediated by both direct tumor cell killing due to
      apoptosis and indirect tumor cell killing due to vascular-disrupting mechanisms.
      The clinical translation of cell and gene therapy approaches represent a
      challenging strategy that might achieve systemic tumor targeting and increased
      intratumor delivery of the therapeutic agent.

PMID- 17438089
TI  - Vorinostat for treatment of cutaneous manifestations of advanced primary
      cutaneous T-cell lymphoma.
AB  - PURPOSE: To discuss vorinostat approval for treatment of cutaneous manifestations
      of advanced cutaneous T-cell lymphoma (CTCL). EXPERIMENTAL DESIGN: Data from 1
      single-arm, open-label, multicenter pivotal trial and 11 other trials submitted
      to support the new drug application for vorinostat in the treatment of advanced
      primary CTCL were reviewed. The pivotal trial assessed responses by changes in
      overall skin disease score using a severity-weighted assessment tool (SWAT).
      Vorinostat could be considered active in CTCL if observed response rate was at
      least 20% and the lower bound of the corresponding 95% confidence interval (95%
      CI) excluded 5%. Patients reported pruritus relief using a questionnaire and a
      visual analogue scale. RESULTS: The pivotal trial enrolled 74 patients with stage
      IB or higher CTCL. Median number of prior treatments was 3, and 61 patients (82%)
      had stage IIB or higher disease. The objective response rate in the skin disease
      assessed by change in the overall SWAT score from the baseline was 30% (95% CI,
      18.5 to 42.6) in patients with stage IIB or higher disease. Median response
      duration (end of response defined by 50% increase in SWAT score from the nadir)
      was 168 days. Median time to tumor progression was 148 days for overall
      population and 169 days for patients with stage IIB or higher disease. Assessment
      of pruritus relief was considered unreliable. CONCLUSIONS: Vorinostat showed
      activity in CTCL, and skin responses were a clinical benefit. Vorinostat was
      approved for treatment of cutaneous manifestations of CTCL. A nonblinded, single
      arm trial did not allow a reliable assessment of pruritus relief.

PMID- 17438090
TI  - Higher frequency of diploidy in young-onset microsatellite-stable colorectal
      cancer.
AB  - PURPOSE: Colorectal carcinoma (CRC) can be divided into two nonoverlapping
      groups: those that are chromosomally unstable but microsatellite stable (MSS
      CIN+) and those that are chromosomally stable but microsatellite unstable (MSI
      CIN-). However, a third group with neither chromosome nor microsatellite
      instability (MSS CIN-) makes a substantial contribution to the total CRC burden.
      The clinicopathologic features of MSS CIN- CRC are not well delineated. We
      assessed the relationship between age and chromosomal instability (CIN) status as
      measured by ploidy and allelic imbalance in a series of MSS tumors. EXPERIMENTAL
      DESIGN: We studied a prospectively collected series of CRC patients at Mayo
      Clinic Rochester. A total of 84 samples of MSS CRC in patients <or=50 years old
      were identified between 1994 and 1997. A consecutive series of 90 MSS CRC in
      patients >or=65 years old served as a comparison group. CIN status was assessed
      using two techniques: ploidy analysis by flow cytometry and small chromosome
      changes as measured by genomewide fractional allelic imbalance. RESULTS: CRC in
      the young-onset group was more likely to involve the rectum and to be high stage.
      MSS tumors in the young-onset group were more often diploid (46%) than those in
      older patients (26%; P = 0.006). This difference was maintained in the subset of
      MSS CRC that were high stage (42% versus 18%; P = 0.02) and in rectal cancers
      (50% versus 23%; P = 0.04). CONCLUSION: A greater proportion of young patients
      with MSS CRC has diploid tumors than patients who develop MSS CRC over age 65.

PMID- 17438091
TI  - The triple negative paradox: primary tumor chemosensitivity of breast cancer
      subtypes.
AB  - PURPOSE: Gene expression analysis identifies several breast cancer subtypes. We
      examined the relationship of neoadjuvant chemotherapy response to outcome among
      these breast cancer subtypes. EXPERIMENTAL DESIGN: We used immunohistochemical
      profiles [human epidermal growth factor receptor 2-positive (HER2+)/hormone
      receptor-negative for HER2+/estrogen receptor-negative (ER-), hormone receptor
      and HER2- for basal-like, hormone receptor-positive for luminal] to subtype a
      prospectively maintained data set of patients with breast cancer treated with
      neoadjuvant anthracycline-based (doxorubicin plus cyclophosphamide, AC)
      chemotherapy. We analyzed each subtype for clinical and pathologic response to
      neoadjuvant chemotherapy and examined the relationship of response to distant
      disease-free survival and overall survival. RESULTS: Of the 107 patients tested,
      34 (32%) were basal-like, 11 (10%) were HER2+/ER-, and 62 (58%) were luminal.
      After neoadjuvant AC, 75% received subsequent chemotherapy and all received
      endocrine therapy if hormone receptor-positive. The chemotherapy regimen and
      pretreatment stage did not differ by subtype. Clinical response to AC was higher
      among the HER2+/ER- (70%) and basal-like (85%) than the luminal subtypes (47%; P
      < 0.0001). Pathologic complete response occurred in 36% of HER2+/ER-, 27% of
      basal-like, and 7% of luminal subtypes (P = 0.01). Despite initial
      chemosensitivity, patients with the basal-like and HER2+/ER- subtypes had worse
      distant disease-free survival (P = 0.04) and overall survival (P = 0.02) than
      those with the luminal subtypes. Regardless of subtype, only 2 of 17 patients
      with pathologic complete response relapsed. The worse outcome among basal-like
      and HER+/ER- subtypes was due to higher relapse among those with residual disease
      (P = 0.003). CONCLUSIONS: Basal-like and HER2+/ER- subtypes are more sensitive to
      anthracycline-based neoadjuvant chemotherapy than luminal breast cancers.
      Patients that had pathologic complete response to chemotherapy had a good
      prognosis regardless of subtype. The poorer prognosis of basal-like and HER2+/ER-
      breast cancers could be explained by a higher likelihood of relapse in those
      patients in whom pathologic complete response was not achieved.

PMID- 17438092
TI  - ADAM-17 expression in breast cancer correlates with variables of tumor
      progression.
AB  - The ADAMs are a family of membrane proteins possessing a disintegrin and
      metalloprotease domain. One of their main functions is shedding of membrane
      proteins. The aim of this study was to test the hypothesis that ADAM-17 (also
      known as tumor necrosis factor-alpha converting enzyme) is involved in breast
      cancer progression. Overexpression of ADAM-17 in MCF-7 breast cancer cells
      increased in vitro invasion and proliferation, whereas down-regulation of ADAM-17
      expression in MDA-MB-435 cells decreased invasion and proliferation. At both mRNA
      and protein levels, ADAM-17 expression was significantly up-regulated in breast
      cancer compared with normal breast tissue. Using Western blotting, ADAM-17
      protein in breast cancer was shown to exist in two forms migrating with
      approximate molecular masses of 100 and 120 kDa. Based on their known molecular
      mass, these bands were taken to represent the active and precursor forms of ADAM
      17, respectively. The proportion of active to total ADAM-17 increased
      progressively from normal breast tissue to primary breast cancer to lymph node
      metastases (P = 0.017, Kruskal-Wallis test). In primary cancers, the active form
      was expressed more frequently in node-positive compared with node-negative tumors
      (P = 0.034, chi(2) test). Furthermore, in primary carcinomas, both forms of ADAM
      17 correlated significantly (Spearman correlation analysis) with levels of
      urokinase plasminogen activator (precursor form: r = 0.246, P = 0.032, n = 83 and
      active form: r = 0.428, P = 0.0001, n = 83) and proliferating cell nuclear
      antigen (precursor form: r = 0.524, P < 0.0001, n = 73 and active form: r =
      0.365, P = 0.002, n = 73). Our results support the hypothesis that ADAM-17 is
      involved in breast cancer progression.

PMID- 17438093
TI  - Reciprocal regulation of SOCS 1 and SOCS3 enhances resistance to ionizing
      radiation in glioblastoma multiforme.
AB  - PURPOSE: The expression of suppressors of cytokine signaling 1 (SOCS1) and SOCS3
      genes is dysregulated in several solid tumors, causing aberrant activation of
      cell growth and survival signaling pathways. In this study, we analyzed SOCS1 and
      SOCS3 gene expression in glioblastoma multiforme (GBM) and studied the role of
      each protein in GBM cell signaling and radiation resistance. EXPERIMENTAL DESIGN:
      SOCS1 and SOCS3 gene expression was analyzed in 10 GBM cell lines by reverse
      transcription-PCR and Western blotting. SOCS3 expression was also studied in 12
      primary GBM tissues by immunohistochemistry. The methylation status of the SOCS1
      and SOCS3 loci was determined by methylation-specific PCR. Extracellular signal
      regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) activation in GBM
      cell lines overexpressing SOCS1 or lacking SOCS3 was determined by phosphorylated
      specific Western blotting. Radiation responses in SOCS1-positive and SOCS3
      deficient GBM cell lines and fibroblasts from wild-type and SOCS1 or SOCS3
      knockout mice were studied in a clonogenic survival assay. RESULTS: All GBM cell
      lines tested lacked SOCS1 expression, whereas GBM cell lines and primary GBM
      tumor samples constitutively expressed SOCS3. SOCS1 gene repression was linked to
      hypermethylation of the SOCS1 genetic locus in GBM cells. Reintroduction of SOCS1
      or blocking SOCS3 expression sensitized cells to radiation and decreased the
      levels of activated ERK MAPKs in GBM cells. CONCLUSIONS: SOCS1 and SOCS3 are
      aberrantly expressed in GBM cell lines and primary tissues. Altered SOCS gene
      expression leads to increased cell signaling through the ERK-MAPK pathway and may
      play a role in disease pathogenesis by enhancing GBM radioresistance.

PMID- 17438094
TI  - Role of CD14 promoter polymorphisms in Helicobacter pylori infection--related
      gastric carcinoma.
AB  - PURPOSE: Genetic variation in CD14 may affect CD14 expression and susceptibility
      to Helicobacter pylori infection-related cancers. This study examined functional
      single nucleotide polymorphisms (SNP) in the CD14 promoter and their associations
      with risk of developing gastric carcinoma in relation to H. pylori infection.
      EXPERIMENTAL DESIGN: Thirty individual DNAs were sequenced to identify variants,
      and the function of the variants was examined by reporter gene assays. Genotypes
      and haplotypes were analyzed in 470 patients and 470 controls, and odds ratios
      (OR) and 95% confidence intervals (95% CI) were estimated by logistic regression.
      Serologic H. pylori antibody and soluble CD14 (sCD14) levels were measured by
      ELISA. RESULTS: Two SNPs (-651C>T and -260C>T) were identified, of which the 
      260CT and -260TT genotypes were associated with elevated risk of gastric
      carcinoma (OR, 1.77; 95% CI, 1.09-2.85 and OR, 1.95; 95% CI, 1.20-3.16,
      respectively). Haplotype analysis suggested a synergistic effect of the two SNPs
      (OR for the T(-651)-T(-260) haplotype, 3.39 versus OR for the C(-651)-T(-260)
      haplotype, 1.45; P = 0.02), which is consistent with reporter gene assays. A
      multiplicative joint effect between H. pylori infection and -260C>T polymorphism
      was observed (OR for the presence of both -260TT genotype and H. pylori
      infection, 4.03; 95% CI, 1.80-9.04). Patients had significantly higher sCD14 than
      controls (1,866 +/- 2,535 ng/mL versus 1,343 +/- 2,119 ng/mL; P < 0.001), and
      this difference was associated with the CD14 -260 polymorphism and H. pylori
      infection. CONCLUSIONS: Functional polymorphism in CD14 is associated with
      greater risk of H. pylori-related gastric carcinoma, which might be mediated by
      elevated sCD14.

PMID- 17438095
TI  - c-Kit/PDGFRA gene status alterations possibly related to primary imatinib
      resistance in gastrointestinal stromal tumors.
AB  - PURPOSE: To correlate morphologic changes with molecular, biochemical, and
      cytogenetic profiles in gastrointestinal stromal tumor (GIST) patients before and
      after imatinib treatment. EXPERIMENTAL DESIGN: We investigated 132 tumor samples
      obtained from 35 patients with advanced disease who underwent resective surgery
      after imatinib treatment according to the European Organization for Research and
      Treatment of Cancer-Soft Tissue and Bone Sarcoma Group protocol. On the basis of
      imaging findings, 27 patients were responders and 8 progressors, and retaining
      this radiological subdivision, we analyzed posttreatment morphologic changes
      correlating them with molecular, biochemical, and cytogenetic analyses. RESULTS:
      On the basis of morphology (residual viable cellularity/proliferation markers),
      three subgroups were identified showing high, moderate, or low response. All of
      the progressing cases clustered in the low-response subgroup, whereas the
      responding cases were distributed in all three subgroups. The correlation between
      morphology and the molecular findings showed that secondary mutations segregated
      with the low-response subgroup, whereas c-Kit primary resistance mutations were
      randomly distributed in the three subgroups. Fluorescence in situ hybridization
      analysis of c-Kit/PDGFRA genes showed that all of the progressing cases were
      disomic. Referring to morphology, among the responding cases, a disomic pattern
      was mainly restricted to the high responders, whereas the moderate and low
      responders were aneusomic. Comparison of post-imatinib genomic profiles with the
      23 available primary tumors showed that 17 cases carried the same cytogenetic
      pattern. Overall, 12 of the 27 primary tumors presented a gain/loss of c
      Kit/PDGFRA gene copy number. CONCLUSIONS: Our findings show that c-Kit/PDGFRA
      genomic alterations were present at disease onset in 1/3 of the examined cases.
      They therefore represent an early event possibly related to primary imatinib
      resistance in GISTs.

PMID- 17438096
TI  - Predicting hepatocellular carcinoma by detection of aberrant promoter methylation
      in serum DNA.
AB  - PURPOSE: Most hepatocellular carcinomas (HCC) are diagnosed at an advanced stage.
      Hypermethylation of CpG islands in promoter regions is now recognized as an
      important early event in carcinogenesis and detection of methylated DNA has been
      suggested as a potential biomarker for early detection of cancer. There are no
      studies on epigenetic changes in samples from HCC patients before diagnosis. We
      explored the possible diagnostic value of aberrant promoter hypermethylation of
      three tumor suppressor genes in serum DNA for early detection of HCC.
      EXPERIMENTAL DESIGN: Aberrant promoter hypermethylation was investigated in DNA
      isolated from the serum of 50 HCC patients who provided repeated blood samples
      before diagnosis and 50 controls enrolled in a cancer screen program in Taiwan.
      Methylation-specific PCR was used to determine the methylation status of p16,
      p15, and ras association domain family 1A (RASSF1A). RESULTS: Among cases,
      aberrant methylation was found in serum DNA 1 to 9 years before clinical HCC
      diagnosis. RASSF1A had the highest frequency of hypermethylation with 35 (70%)
      cases having at least one positive sample compared with 22 (44%) for p16 and 12
      (22%) for p15. Six subjects were hypermethylation negative for all three genes.
      For the 50 controls, promoter hypermethylation was found in three and two
      subjects for RASSF1A and p16, respectively; none had methylation of p15. A
      receiver operating characteristic curve that included clinical risk factors (age,
      HBsAg status, anti-hepatitis C virus status, smoking, and alcohol status) and
      hypermethylation biomarkers gave an overall predictive accuracy of 89% with
      sensitivity and specificity 84% and 94%, respectively. CONCLUSIONS: The analysis
      of epigenetic changes on RASSF1A, p16, and p15 tumor suppressor genes in serum
      DNA may be a valuable biomarkers for early detection in populations at high risk
      of HCC.

PMID- 17438097
TI  - Serum cytokine profiling as a diagnostic and prognostic tool in ovarian cancer: a
      potential role for interleukin 7.
AB  - PURPOSE: To evaluate if serum cytokine levels could be used as diagnostic or
      prognostic markers in ovarian cancer. EXPERIMENTAL DESIGN: A cytokine bead array
      was done to simultaneously analyze 14 cytokines in the sera of 187 ovarian cancer
      patients with complete clinicopathologic data and follow-up, 45 patients with
      benign ovarian tumors, and 50 healthy controls. Serum levels of the well-known
      serum tumor marker CA-125 were routinely measured in all patients. RESULTS: Serum
      levels of CA-125, interleukin 6 (IL-6), IL-7, and IL-10 were elevated in ovarian
      cancer patients compared with patients with benign ovarian tumors. Analyzing the
      cytokines in combination with CA-125 showed that a combination of IL-7 and CA-125
      serum levels could accurately predict 69% of the ovarian cancer patients, without
      falsely classifying patients with benign pelvic mass. The cytokines IL-6, IL-7,
      IL-8, IL-10, monocyte chemotactic protein-1 (MCP-1), and IP-10 and CA-125 were
      associated with disease-free and overall survival in univariate analysis. In
      multivariate analysis, IL-7 and IP-10 were independent predictors of overall
      survival, although after inclusion of the clinicopathologic parameters, only
      stage and residual disease remained as independent predictors of survival.
      CONCLUSIONS: IL-7 levels were found to be strongly associated with ovarian cancer
      and could be used in combination with CA-125 to distinguish between malignant and
      benign ovarian tumors.

PMID- 17438098
TI  - Systemic interleukin-2 and adoptive transfer of lymphokine-activated killer cells
      improves antibody-dependent cellular cytotoxicity in patients with relapsed B
      cell lymphoma treated with rituximab.
AB  - PURPOSE: Murine models have shown that antibody-dependent cellular cytotoxicity
      (ADCC) can be improved with addition of lymphokine-activated killer (LAK) cells
      to monoclonal antibodies. A pilot trial of rituximab and LAK cells in patients
      with rituximab-refractory CD20+ lymphoma was conducted to evaluate this approach.
      EXPERIMENTAL DESIGN: Ten patients received 3 million units/m2 of interleukin-2
      (IL-2) i.v. qd on days 1 to 5 and leukapheresed on days 8, 9, and 10. The
      leukapheresis product was cultured with IL-2 for 48 h to produce LAK cells.
      Patients then received 375 mg/m2 i.v. rituximab and LAK cells on days 10, 11, and
      12. The patients also received 3 million units/m2 of IL-2 i.v. for 5 days
      starting day 10. For safety purposes, the first three patients did not receive
      any LAK cell infusions. RESULTS: The LAK cell infusions improved the ADCC
      activity of peripheral blood lymphocytes compared with pretreatment activity and
      prevented the decline in ADCC seen after infusion of rituximab alone. Therapy was
      well tolerated and the most clinically significant toxicities were fever and
      fatigue. Two patients achieved a partial remission and five had stable disease.
      CONCLUSIONS: The results from these studies suggest that the addition of LAK
      cells to rituximab augments ADCC in patients with rituximab-refractory lymphoma.

PMID- 17438099
TI  - Phase II trials published in 2002: a cross-specialty comparison showing
      significant design differences between oncology trials and other medical
      specialties.
AB  - PURPOSE: Phase II trials play an essential role in drug development pathway, and
      their conclusions often impact the decision to embark on large, pivotal trials.
      However, the determination of agent activity is highly dependent on trial design.
      Formal comparisons of phase II trial designs across medical specialties are
      uncommon. We hypothesized that there are significant differences in the design of
      trials conducted by oncologists and those conducted by other medical and surgical
      specialties. EXPERIMENTAL DESIGN: We screened MEDLINE for the abstracts of phase
      II trials published in 2002. All abstracts were analyzed and classified by a
      priori defined variables, including study type, intervention, subspecialty,
      journal impact factor, method of control, and study conclusions. RESULTS: Our
      search yielded 703 abstracts of phase II trials published in 2002. A total of
      586/703 (83%) were trials on antineoplastic agents. Twenty percent (143/703) of
      the trials included explicit control subjects. Oncology trials, as compared with
      all trials done by other specialties, were significantly less likely to use
      control subjects (13% versus 56%, P < 0.001) and were less likely to conclude
      that the investigational intervention was safe and efficacious and/or worthy of
      additional investigation (76% versus 89%, P < 0.01). CONCLUSIONS: There are
      significant differences in the phase II trials published in oncology compared
      with those conducted by other medical and surgical specialties. The impact that
      such differences have on the efficiency of drug development should be
      investigated.

PMID- 17438100
TI  - Phase I study of aerosolized SLIT cisplatin in the treatment of patients with
      carcinoma of the lung.
AB  - PURPOSE: To investigate the safety and pharmacokinetics of aerosolized Sustained
      Release Lipid Inhalation Targeting (SLIT) Cisplatin in patients with lung
      carcinoma. EXPERIMENTAL DESIGN: Phase I, dose-escalating study of SLIT Cisplatin
      given in two sessions daily. Safety data, including laboratory variables, adverse
      events, pulmonary function tests, and radiographic imaging, were collected and
      analyzed for all patients to determine toxicity. Pharmacokinetic monitoring was
      done during the first course. RESULTS: Seventeen patients and one tracheostomy
      patient on compassionate use received treatment. Aerosolized cisplatin was well
      tolerated. No dose-limiting toxicity was observed at the maximum delivered dose.
      Safety data showed no hematologic toxicity, nephrotoxicity, ototoxicity, or
      neurotoxicity. Most common adverse events were nausea (64.7%), vomiting (47.1%),
      dyspnea (64.7%), fatigue (64.7%), and hoarseness (47.1%). Pharmacokinetic data
      showed very low plasma platinum levels only with the longest repeated
      inhalations. Common Toxicity Criteria grade 2 decrease in forced expiratory
      volume in one second and diffusing lung capacity for carbon monoxide after one
      course occurred both in two patients and grade one decrease in forced expiratory
      volume in one second and diffusing lung capacity for carbon monoxide in six and
      five patients, respectively. Direct airway deposition via the tracheostomy
      resulted in clinical deterioration after two cycles best described as bronchitis,
      completely reversible within days. Overall response: stable disease in 12
      patients and progressive disease in 4 patients (one patient received one cycle).
      CONCLUSIONS: Aerosolized liposomal cisplatin was found to be feasible and safe.

PMID- 17438101
TI  - Multiplex analysis of serum cytokines in melanoma patients treated with
      interferon-alpha2b.
AB  - PURPOSE: Interferon (IFN)-alpha2b is the only Food and Drug Administration
      approved treatment for operable high-risk melanoma that has been shown to
      significantly and durably prolong relapse-free survival (RFS) of patients with
      stage IIB-III melanoma. Development of reliable serum assays may contribute to
      the development of methods for earlier detection of melanoma and the selection of
      patients who may be most susceptible to current available interventions with
      IFNalpha. EXPERIMENTAL DESIGN: A powerful high-throughput xMAP multiplex
      immunobead assay technology (Luminex Corp., Austin, TX) was used to
      simultaneously test 29 cytokines, chemokines, angiogenic as well as growth
      factors, and soluble receptors in the sera of 179 patients with high-risk
      melanoma and 378 healthy individuals. RESULTS: Serum concentrations of
      interleukin (IL)-1alpha, IL-1beta, IL-6, IL-8, IL-12p40, IL-13, granulocyte
      colony-stimulating factor, monocyte chemoattractant protein 1 (MCP-1), macrophage
      inflammatory protein (MIP)-1alpha, MIP-1beta, IFNalpha, tumor necrosis factor
      (TNF)-alpha, epidermal growth factor, vascular endothelial growth factor (VEGF),
      and TNF receptor II were found to be significantly higher in patients with
      resected high-risk melanoma compared with healthy controls. Bayesian Network
      algorithm classification of the data offered 90% sensitivity at 98% specificity
      with 96.5% of melanoma patients distinguished from healthy individuals. IFN
      alpha2b therapy resulted in a significant decrease of serum levels of
      immunosuppressive and tumor angiogenic/growth stimulatory factors (VEGF,
      epidermal growth factor, and hepatocyte growth factor) and increased levels of
      antiangiogenic IFN-gamma inducible protein 10 (IP-10) and IFN-alpha. Pretreatment
      levels of proinflammatory cytokines IL-1beta, IL-1alpha, IL-6, TNF-alpha, and
      chemokines MIP-1alpha and MIP-1beta were found to be significantly higher in the
      serum of patients with longer RFS values of 1 to 5 and >5 years when compared
      with patients with shorter RFS of <1 year. CONCLUSION: These data show that
      multiplexed analysis of serum biomarkers is useful for the evaluation of
      prognostic markers of clinical outcome and potential predictive markers of
      response to IFN-alpha2b in patients with high-risk operable melanoma.

PMID- 17438102
TI  - Cholecystokinin down-regulation by RNA interference impairs Ewing tumor growth.
AB  - PURPOSE: Tumors of the Ewing family are characterized by chromosomal
      translocations that yield chimeric transcription factors, such as EWS/FLI1, which
      regulate the expression of specific genes that contribute to the malignant
      phenotype. In the present study, we show that cholecystokinin (CCK) is a new
      target of the EWS/FLI1 oncoprotein and assess its functional role in Ewing tumor
      pathogenesis. EXPERIMENTAL DESIGN: Relevant EWS/FLI1 targets were identified
      using a combination of cell systems with inducible EWS/FLI1 expression, Ewing
      tumors and cell lines, microarrays, and RNA interference with doxycycline
      inducible small hairpin RNA (shRNA) vectors. A doxycycline-inducible CCK-shRNA
      vector was stably transfected in A673 and SK-PN-DW Ewing cell lines to assess the
      role of CCK in cell proliferation and tumor growth. RESULTS: Microarray analysis
      revealed that CCK was up-regulated by EWS/FLI1 in HeLa cells. CCK was
      overexpressed in Ewing tumors as compared with other pediatric malignancies such
      as rhabdomyosarcoma and neuroblastoma, with levels close to those detected in
      normal tissues expressing the highest levels of CCK. Furthermore, EWS/FLI1
      knockdown in A673 and SK-PN-DW Ewing cells using two different doxycycline
      inducible EWS/FLI1-specific shRNA vectors down-regulated CCK mRNA expression and
      diminished the levels of secreted CCK, showing that CCK is a EWS/FLI1 specific
      target gene in Ewing cells. A doxycycline-inducible CCK-specific shRNA vector
      successfully down-regulated CCK expression, reduced the levels of secreted CCK in
      Ewing cell lines, and inhibited cell growth and proliferation in vitro and in
      vivo. Finally, we show that Ewing cell lines and tumors express CCK receptors and
      that the growth inhibition produced by CCK silencing can be rescued by culturing
      the cells with medium containing CCK. CONCLUSIONS: Our data support the
      hypothesis that CCK acts as an autocrine growth factor stimulating the
      proliferation of Ewing cells and suggest that therapies targeting CCK could be
      promising in the treatment of Ewing tumors.

PMID- 17438103
TI  - Silencing of hypoxia inducible factor-1alpha by RNA interference attenuates human
      glioma cell growth in vivo.
AB  - PURPOSE: Higher-grade gliomas are distinguished by increased vascular endothelial
      cell proliferation and peritumoral edema. These are thought to be instigated by
      vascular endothelial growth factor, which, in turn, is regulated by cellular
      oxygen tension. Hypoxia inducible factor-1alpha (HIF-1alpha) is a main responder
      to intracellular hypoxia and is overexpressed in many human cancers, including
      gliomas. EXPERIMENTAL DESIGN: We investigated the role of HIF-1alpha in glioma
      growth in vivo using RNA interference (RNAi) in U251, U87, and U373 glioma cells.
      RESULTS: We found that RNAi can be used to significantly attenuate glioma growth
      by reducing HIF-1alpha levels constitutively using short hairpin RNAs and
      transiently using small interfering RNAs (siRNA). HIF-1alpha levels on average
      were reduced 55% in normoxia and 71% in hypoxia. Vascular endothelial growth
      factor and GLUT-1 levels were reduced 81% and 71%, respectively, in the stable
      HIF-1alpha-reduced clones. These clones showed significant growth attenuation (up
      to 73%) compared with negative controls when grown in vivo in mouse flanks.
      Cellular proliferation was also reduced significantly, as determined by MIB-1
      staining. Treating gliomas grown in mouse flank transiently with siRNA against
      HIF-1alpha by intratumoral injection resulted in a significant reduction of HIF
      1alpha activity. This activity was followed using a hypoxia-responsive luciferase
      construct that enabled hypoxia imaging in vivo. Tumor volume in these siRNA
      injection experiments was reduced by 50% over the negative controls. CONCLUSIONS:
      These results indicate that transient RNAi directed against HIF-1alpha can
      effectively curb glioma growth in vivo.

PMID- 17438104
TI  - In vivo imaging of oral mucositis in an animal model using optical coherence
      tomography and optical Doppler tomography.
AB  - PURPOSE: To assess noninvasive optical coherence tomography (OCT) and optical
      Doppler tomography (ODT) for early detection and evaluation of chemotherapy
      induced oral mucositis. EXPERIMENTAL DESIGN: Cheek pouches of 10 Syrian golden
      hamsters were imaged using OCT/ODT during development of chemotherapy-induced
      mucositis. I.p. injections of 5-fluorouracil and mechanical irritation induced
      oral lesions. At 2, 4, 7, and 11 days, one hamster was sacrificed and processed
      for histopathology. OCT images were visually examined; ODT results were
      semiquantified. Imaging data were compared with histologic findings. RESULTS:
      During the development of mucositis, OCT/ODT identified the following events: (a)
      change in epithelial thickness (beginning on day 2), (b) loss of surface
      keratinized layer continuity (beginning on day 4), (c) loss of epithelial (day 4
      onwards) and submucosal integrity (day 7 onwards), (d) changes in axial blood
      flow velocity (increased on days 2 and 4; decreased on day 7), and (e) changes in
      blood vessel size (diameter doubled on day 2; quadrupled on day 4; unchanged on
      day 7). The semiquantitative imaging-based scoring system identified the severity
      of mucositis as defined by histopathology. The combination of imaging criteria
      used allowed for the detection of early, intermediate, and late mucositic
      changes. Imaging data gave higher scores compared with clinical scores early on,
      suggesting that the imaging-based diagnostic scoring was more sensitive to early
      mucositic change than the clinical scoring system. Once mucositis was
      established, imaging and clinical scores converged. CONCLUSION: OCT/ODT
      identified chemotherapy-induced oral changes before their clinical manifestation,
      and the proposed scoring system for oral mucositis was validated for the
      semiquantification of mucositic change.

PMID- 17438105
TI  - A novel chromogranin-A promoter-driven oncolytic adenovirus for midgut carcinoid
      therapy.
AB  - PURPOSE: The use of replication-selective oncolytic adenoviruses is an emerging
      therapeutic approach for cancer, which thus far has not been employed for
      carcinoids. We therefore constructed Ad[CgA-E1A], a novel replication-selective
      oncolytic adenovirus, where the chromogranin A (CgA) promoter controls expression
      of the adenoviral E1A gene. EXPERIMENTAL DESIGN: The Ad[CgA-E1A] virus was
      evaluated for E1A protein expression, replication ability, and cytolytic activity
      in various cell lines. It was also evaluated for treatment of xenografted human
      carcinoid tumors in nude mice. To use Ad[CgA-E1A] for the treatment of carcinoid
      liver metastases, it is important that normal hepatocytes do not support virus
      replication to minimize hepatotoxicity. We therefore evaluated CgA protein
      expression in normal hepatocytes. We also evaluated CgA gene expression in normal
      hepatocytes and microdissected tumor cells from carcinoid metastases. RESULTS: We
      found that Ad[CgA-E1A] replicates similarly to wild-type virus in tumor cells
      with neuroendocrine features, including the BON carcinoid cell line and the SH-SY
      5Y neuroblastoma cell lines, whereas it is attenuated in other cell types. Thus,
      cells where the CgA promoter is active are selectively killed. We also found that
      Ad[CgA-E1A] is able to suppress fast-growing human BON carcinoid tumors in nude
      mice. Furthermore, CgA is highly expressed in microdissected cells from carcinoid
      metastases, whereas it is not expressed in normal hepatocytes. CONCLUSION: Ad[CgA
      E1A] is an interesting agent for the treatment of carcinoid liver metastases in
      conjunction with standard therapy for these malignancies.

PMID- 17438106
TI  - The tyrosine kinase inhibitor imatinib mesylate enhances the efficacy of
      photodynamic therapy by inhibiting ABCG2.
AB  - PURPOSE: The ATP-binding cassette protein ABCG2 (breast cancer resistance
      protein) effluxes some of the photosensitizers used in photodynamic therapy (PDT)
      and, thus, may confer resistance to this treatment modality. Tyrosine kinase
      inhibitors (TKI) can block the function of ABCG2. Therefore, we tested the
      effects of the TKI imatinib mesylate (Gleevec) on photosensitizer accumulation
      and in vitro and in vivo PDT efficacy. EXPERIMENTAL DESIGN: Energy-dependent
      photosensitizer efflux and imatinib mesylate's effects on intracellular
      accumulation of clinically used second- and first-generation photosensitizers
      were studied by flow cytometry in murine and human cells with and without ABCG2
      expression. Effects of ABCG2 inhibition on PDT were examined in vitro using cell
      viability assays and in vivo measuring photosensitizer accumulation and time to
      regrowth in a RIF-1 tumor model. RESULTS: Energy-dependent efflux of 2-(1
      hexyloxethyl)-2-devinyl pyropheophorbide-a (HPPH, Photochlor), endogenous
      protoporphyrin IX (PpIX) synthesized from 5-aminolevulenic acid, and the
      benzoporphyrin derivative monoacid ring A (BPD-MA, Verteporfin) was shown in
      ABCG2+ cell lines, but the first-generation multimeric photosensitizer porfimer
      sodium (Photofrin) and a novel derivative of HPPH conjugated to galactose were
      minimally transported. Imatinib mesylate increased accumulation of HPPH, PpIX,
      and BPD-MA from 1.3- to 6-fold in ABCG2+ cells, but not in ABCG2- cells, and
      enhanced PDT efficacy both in vitro and in vivo. CONCLUSIONS: Second-generation
      clinical photosensitizers are transported out of cells by ABCG2, and this effect
      can be abrogated by coadministration of imatinib mesylate. By increasing
      intracellular photosensitizer levels in ABCG2+ tumors, imatinib mesylate or other
      ABCG2 transport inhibitors may enhance efficacy and selectivity of clinical PDT.

PMID- 17438107
TI  - The human T-box mesodermal transcription factor Brachyury is a candidate target
      for T-cell-mediated cancer immunotherapy.
AB  - PURPOSE: Identification of tumor antigens is essential in advancing immune-based
      therapeutic interventions in cancer. Particularly attractive targets are those
      molecules that are selectively expressed by malignant cells and that are also
      essential for tumor progression. EXPERIMENTAL DESIGN AND RESULTS: We have used a
      computer-based differential display analysis tool for mining of expressed
      sequence tag clusters in the human Unigene database and identified Brachyury as a
      novel tumor antigen. Brachyury, a member of the T-box transcription factor
      family, is a key player in mesoderm specification during embryonic development.
      Moreover, transcription factors that control mesoderm have been implicated in the
      epithelial-mesenchymal transition (EMT), which has been postulated to be a key
      step during tumor progression to metastasis. Reverse transcription-PCR analysis
      validated the in silico predictions and showed Brachyury expression in tumors of
      the small intestine, stomach, kidney, bladder, uterus, ovary, and testis, as well
      as in cell lines derived from lung, colon, and prostate carcinomas, but not in
      the vast majority of the normal tissues tested. An HLA-A0201 epitope of human
      Brachyury was identified that was able to expand T lymphocytes from blood of
      cancer patients and normal donors with the ability to lyse Brachyury-expressing
      tumor cells. CONCLUSIONS: To our knowledge, this is the first demonstration that
      (a) a T-box transcription factor and (b) a molecule implicated in mesodermal
      development, i.e., EMT, can be a potential target for human T-cell-mediated
      cancer immunotherapy.

PMID- 17438108
TI  - HLA-DQB1*02-restricted HPV-16 E7 peptide-specific CD4+ T-cell immune responses
      correlate with regression of HPV-16-associated high-grade squamous
      intraepithelial lesions.
AB  - PURPOSE: The fact that up to 30% of established high-grade squamous
      intraepithelial lesions (HSIL) of the cervix regress spontaneously presents the
      opportunity to identify clinically relevant human papillomavirus (HPV) viral
      epitopes associated with disease outcome. Two human HPV antigens, E6 and E7, are
      functionally required for initiation and maintenance of cervical cancer precursor
      lesions and invasive cervical cancer. The identification and characterization of
      endogenously processed HPV antigenic epitopes in closely characterized patient
      cohorts will provide insight into the reasons for success or failure of
      therapeutic approaches. EXPERIMENTAL DESIGN: We characterized the HPV-16 E6/E7
      specific T-cell epitopes using E6/E7 overlapping peptide pools with peripheral
      blood lymphocytes obtained from normal healthy donors. We then analyzed the
      difference in the HPV-16 T-cell immune responses in HPV-16+ HSIL patients with or
      without spontaneous regression of lesions using the statistical methods. RESULTS:
      We have identified an HPV-16 E7-specific CD4+ T-cell epitope [amino acids (aa) 71
      85] that was restricted by HLA-DQB1*0201. Analysis of peripheral blood
      lymphocytes obtained from 14 HLA-DQB1*02 patients with HPV-16+ HSILs showed that
      the HPV-16+ E7 peptide (aa 71-85)-specific CD4+ T-cell immune response was
      significantly higher in the group of patients with regression compared with the
      patients without regression (P value <0.05). CONCLUSIONS: The HPV-16 E7 peptide
      specific CD4+ T-cell immune response correlates with spontaneous regression of
      established HPV16+ HSILs. Thus, this E7 epitope may be useful for the
      characterization of HPV-specific immune responses in patients infected with HPV
      16 or immunized with HPV vaccines.

PMID- 17438109
TI  - Activated pregnenolone X-receptor is a target for ketoconazole and its analogs.
AB  - PURPOSE: Variations in biotransformation and elimination of microtubule-binding
      drugs are a major cause of unpredictable side effects during cancer therapy.
      Because the orphan receptor, pregnenolone X-receptor (PXR), coordinately
      regulates the expression of paclitaxel metabolizing and transport enzymes,
      controlling this process could improve therapeutic outcome. EXPERIMENTAL DESIGN:
      In vitro RNA-, protein-, and transcription-based assays in multiple cell lines
      derived from hepatocytes and PXR wild-type and null mouse studies were employed
      to show the effects of ketoconazole and its analogues on ligand-activated PXR
      mediated gene transcription and translation. RESULTS: The transcriptional
      activation of genes regulating biotransformation and transport by the liganded
      human nuclear xenobiotic receptor, PXR, was inhibited by the commonly used
      antifungal ketoconazole and related azole analogs. Mutations at the AF-2 surface
      of the human PXR ligand-binding domain indicate that ketoconazole may interact
      with specific residues outside the ligand-binding pocket. Furthermore, in
      contrast to that observed in PXR (+/+) mice, genetic loss of PXR results in
      increased (preserved) blood levels of paclitaxel. CONCLUSIONS: These studies show
      that some azole compounds repress the coordinated activation of genes involved in
      drug metabolism by blocking PXR activation. Because loss of PXR maintains blood
      levels of paclitaxel upon chronic dosing, ketoconazole analogues may also serve
      to preserve paclitaxel blood levels on chronic dosing of drugs. Our observations
      may facilitate new strategies to improve the clinical efficacy of drugs and to
      reduce therapeutic side effects.

PMID- 17438110
TI  - Proteomics of canine lymphoma identifies potential cancer-specific protein
      markers.
AB  - PURPOSE: Early diagnosis of cancer is crucial for the success of treatment of the
      disease, and there is a need for markers whose differential expression between
      disease and normal tissue could be used as a diagnostic tool. Spontaneously
      occurring malignancies in pets provide a logical tool for translational research
      for human oncology. Lymphoma, one of the most common neoplasms in dogs, is
      similar to human non-Hodgkin's lymphoma and could serve as an experimental model
      system. EXPERIMENTAL DESIGN: Thirteen lymph nodes from normal dogs and 11 lymph
      nodes from dogs with B-cell lymphoma were subjected to proteomic analysis using
      two-dimensional PAGE separation and matrix-assisted laser desorption/ionization
      time-of-flight analysis. RESULTS: A total of 93 differentially expressed spots
      was subjected to matrix-assisted laser desorption/ionization time-of-flight
      tandem mass spectrometry analysis, and several proteins that showed differential
      expression were identified. Of these, prolidase (proline dipeptidase),
      triosephosphate isomerase, and glutathione S-transferase were down-regulated in
      lymphoma samples, whereas macrophage capping protein was up-regulated in the
      lymphoma samples. CONCLUSIONS: These proteins represent potential markers for the
      diagnosis of lymphoma and should be further investigated in human samples for
      validation of their utility as diagnostic markers.

PMID- 17438111
TI  - Characterization and magnetic resonance imaging of a rat model of human B-cell
      central nervous system lymphoma.
AB  - PURPOSE: The incidence of primary central nervous system lymphoma (PCNSL) is
      increasing. Therapeutic approaches remain controversial. An animal model that
      mimics the clinical situation would be useful for evaluating PCNSL biology and
      treatment. EXPERIMENTAL DESIGN: Nude rats received intracerebral (caudate
      nucleus, n = 49) or intraventricular (n = 4) inoculation of human B-lymphoma cell
      line MC116. Two to five weeks after tumor inoculation, magnetic resonance imaging
      (MRI) was done (n = 24), and rat brains were assessed for pathology. Five rats
      each received whole-brain radiotherapy (WBRT, 20 Gy) or high-dose i.v.
      methotrexate (3 g/m2). RESULTS: Intracerebral tumors developed in 84% of
      evaluable animals with no pretreatment, 79% of rats pretreated with 4 Gy total
      body irradiation, and 92% of rats pretreated with cyclophosphamide (300 mg/m2).
      MRI showed abnormal T2 signal and gadolinium enhancement on T1-weighted images,
      consistent with tumor growth 19 to 24 days after inoculation. Tumor cells
      staining positively for B-lymphoma markers infiltrated within the inoculated
      hemisphere, along fiber tracks to the contralateral hemisphere, and along the
      subarachnoid space and ventricles. Tumors showed reactive gliosis.
      Intraventricular tumor cell injection resulted in periventricular parenchymal
      infiltration in both hemispheres. Radiation and methotrexate were effective in
      vitro, but only WBRT was clearly effective after 1 week in the intracerebral
      model. CONCLUSION: This model closely mimics human PCNSL in terms of imaging,
      histology, and treatment sensitivity and will be useful for the development of
      future therapeutic strategies for PCNSL.

PMID- 17438112
TI  - Effect of epidermal growth factor receptor inhibitor class in the treatment of
      head and neck cancer with concurrent radiochemotherapy in vivo.
AB  - PURPOSE: To optimally integrate epidermal growth factor receptor (EGFR)
      inhibitors into the clinical treatment of head and neck cancer, two important
      questions must be answered: (a) does EGFR inhibition add to the effects of
      radiochemotherapy, and (b) if so, which method of inhibiting EGFR is superior (an
      EGFR antibody versus a small molecule tyrosine kinase inhibitor)? We designed an
      in vivo study to address these questions. EXPERIMENTAL DESIGN: Nude mice with
      UMSCC-1 head and neck cancer xenografts received either single, double, or triple
      agent therapy with an EGFR inhibitor (either cetuximab or gefitinib),
      gemcitabine, and/or radiation for 3 weeks. Tumor volumes and animal weights were
      measured for up to 15 weeks. Immunoblotting and immunofluorescent staining were
      done on tumors treated with either cetuximab or gefitinib alone. RESULTS: The
      addition of an EGFR inhibitor significantly delayed the tumor volume doubling
      time, from a median of 40 days with radiochemotherapy (gemcitabine and radiation)
      alone, to 106 days with cetuximab and 66 days with gefitinib (both P < 0.005).
      Cetuximab resulted in significantly less weight loss than gefitinib. Immunoblot
      analysis and immunofluorescent staining of tumors show that although levels of
      phosphorylated AKT and extracellular signal-regulated kinase were decreased
      similarly in response to cetuximab or gefitinib, cetuximab caused prolonged
      suppression of pEGFR, pSTAT3, and Bcl(XL) compared with gefitinib. CONCLUSIONS:
      EGFR inhibition, particularly with cetuximab, improves the effectiveness of
      radiochemotherapy in this model of head and neck cancer. The correlation of
      response with prolonged suppression of EGFR, STAT3, and Bcl(XL) offers the
      possibility that these may be candidate biomarkers for response.

PMID- 17438113
TI  - Ursodeoxycholic acid versus sulfasalazine in colitis-related colon carcinogenesis
      in mice.
AB  - PURPOSE: Inflammation influences carcinogenesis. In the current study, we
      investigated whether ursodeoxycholic acid (UDCA) can inhibit colitis-related
      mouse colon carcinogenesis and compared it with the effects of sulfasalazine.
      EXPERIMENTAL DESIGN: Male CD-1 mice were given a single i.p. injection of
      azoxymethane followed by 1-week oral exposure of 1% dextran sodium sulfate in
      drinking water. They are then maintained on a basal diet mixed with UDCA (0.016%,
      0.08%, or 0.4%) or sulfasalazine (0.05%) for 17 weeks. At week 20, the tumor
      inhibitory effects of both chemicals were assessed by counting the incidence and
      multiplicity of colonic neoplasms. The immunohistochemical expression of the
      proliferating cell nuclear antigen labeling index in colonic epithelial
      malignancies was also assessed. Finally, at week 5, the mRNA expressions for
      cyclooxygenase-2, inducible nitric oxide synthase, peroxisome proliferator
      activated receptor-gamma, and tumor necrosis factor-alpha were measured in
      nontumorous mucosa. RESULTS: Feeding the mice with UDCA at all doses
      significantly inhibited the multiplicity of colonic adenocarcinoma. The treatment
      also significantly lowered the proliferating cell nuclear antigen labeling index
      in the colonic malignancies. UDCA feeding reduced the expression of inducible
      nitric oxide synthase and tumor necrosis factor-alpha mRNA in the colonic mucosa,
      while not significantly affecting the expression of cyclooxygenase-2 mRNA and
      peroxisome proliferator-activated receptor-gamma mRNA. Sulfasalazine caused a
      nonsignificant reduction in the incidence and multiplicity of colonic neoplasia
      and did not affect these mRNA expression. CONCLUSIONS: Our findings suggest that
      UDCA rather than sulfasalazine could serve as an effective suppressing agent in
      colitis-related colon cancer development in mice.

PMID- 17438114
TI  - Polymorphisms of MTHFD, plasma homocysteine levels, and risk of gastric cancer in
      a high-risk Chinese population.
AB  - PURPOSE: Accumulative evidence suggests that folate has a protective effect on
      gastric cancer. The methylenetetrahydrofolate dehydrogenase (MTHFD) plays an
      important role in folate and homocysteine metabolisms, and polymorphisms of MTHFD
      may result in disturbance of the folate-mediated homocysteine pathway. The aim of
      this study is to test the hypothesis that genetic variants of MTHFD and plasma
      homocysteine levels are associated with risk of gastric cancer and modulated by
      genotypes of methylenetetrahydrofolate reductase (MTHFR). EXPERIMENTAL DESIGN: We
      genotyped G1958A and T401C in MTHFD and C677T in MTHFR and detected total plasma
      homocysteine (tHcy) levels in a case-control study of 589 gastric cancer cases
      and 635 cancer-free controls in a high-risk Chinese population. RESULTS: The
      variant genotypes of MTHFD 1958AA and 401CC were associated with a significantly
      increased risk of gastric cancer [adjusted odds ratio (OR), 2.05; 95% confidence
      interval (95% CI), 1.34-3.13 for 1958AA; adjusted OR, 1.43; 95% CI, 1.14-1.80 for
      401CC] compared with 1958GG/GA and 401TT/TC genotypes, respectively. Both of the
      effects were more evident in the subjects carrying MTHFR 677CT/TT genotypes. The
      average tHcy level was significantly higher in gastric cancer cases than in
      controls (P < 0.01), and the upper quartile of tHcy (>13.6 micromol/L) was
      associated with an 82% significantly increased risk of gastric cancer, compared
      with the lowest quartile of tHcy (<or=8.0 micromol/L; adjusted OR, 1.82; 95% CI,
      1.20-2.75). CONCLUSIONS: The strong associations between MTHFD variants and the
      plasma tHcy levels and gastric cancer risk suggest, for the first time, a
      possible gene-environment interaction between genetic variants of folate
      metabolizing genes and high tHcy levels in gastric carcinogenesis.

PMID- 17438115
TI  - Formation of transmembrane helices in vivo--is hydrophobicity all that matters?

PMID- 17438116
TI  - Membrane protein insertion: the biology-physics nexus.

PMID- 17438117
TI  - Experimental measures of amino acid hydrophobicity and the topology of
      transmembrane and globular proteins.

PMID- 17438118
TI  - Partitioning of amino acid side chains into lipid bilayers: results from computer
      simulations and comparison to experiment.

PMID- 17438119
TI  - Elementary mechanisms producing facilitation of Cav2.1 (P/Q-type) channels.
AB  - The regulation of Ca(V)2.1 (P/Q-type) channels by calmodulin (CaM) showcases the
      powerful Ca(2+) decoding capabilities of CaM in complex with the family of Ca(V)1
      2 Ca(2+) channels. Throughout this family, CaM does not simply exert a binary
      on/off regulatory effect; rather, Ca(2+) binding to either the C- or N-terminal
      lobe of CaM alone can selectively trigger a distinct form of channel modulation.
      Additionally, Ca(2+) binding to the C-terminal lobe triggers regulation that
      appears preferentially responsive to local Ca(2+) influx through the channel to
      which CaM is attached (local Ca(2+) preference), whereas Ca(2+) binding to the N
      terminal lobe triggers modulation that favors activation via Ca(2+) entry through
      channels at a distance (global Ca(2+) preference). Ca(V)2.1 channels fully
      exemplify these features; Ca(2+) binding to the C-terminal lobe induces Ca(2+)
      dependent facilitation of opening (CDF), whereas the N-terminal lobe yields
      Ca(2+)-dependent inactivation of opening (CDI). In mitigation of these
      interesting indications, support for this local/global Ca(2+) selectivity has
      been based upon indirect inferences from macroscopic recordings of numerous
      channels. Nagging uncertainty has also remained as to whether CDF represents a
      relief of basal inhibition of channel open probability (P(o)) in the presence of
      external Ca(2+), or an actual enhancement of P(o) over a normal baseline seen
      with Ba(2+) as the charge carrier. To address these issues, we undertake the
      first extensive single-channel analysis of Ca(V)2.1 channels with Ca(2+) as
      charge carrier. A key outcome is that CDF persists at this level, while CDI is
      entirely lacking. This result directly upholds the local/global Ca(2+) preference
      of the lobes of CaM, because only a local (but not global) Ca(2+) signal is here
      present. Furthermore, direct single-channel determinations of P(o) and kinetic
      simulations demonstrate that CDF represents a genuine enhancement of open
      probability, without appreciable change of activation kinetics. This enhanced
      opening mechanism suggests that the CDF evoked during action-potential trains
      would produce not only larger, but longer-lasting Ca(2+) responses, an outcome
      with potential ramifications for short-term synaptic plasticity.

PMID- 17438120
TI  - Probing the cavity of the slow inactivated conformation of shaker potassium
      channels.
AB  - Slow inactivation involves a local rearrangement of the outer mouth of voltage
      gated potassium channels, but nothing is known regarding rearrangements in the
      cavity between the activation gate and the selectivity filter. We now report that
      the cavity undergoes a conformational change in the slow-inactivated state. This
      change is manifest as altered accessibility of residues facing the aqueous cavity
      and as a marked decrease in the affinity of tetraethylammonium for its internal
      binding site. These findings have implications for global alterations of the
      channel during slow inactivation and putative coupling between activation and
      slow-inactivation gates.

PMID- 17438121
TI  - Calcium channels are models of self-control.

PMID- 17438123
TI  - Structural features of the guide:target RNA duplex required for archaeal box C/D
      sRNA-guided nucleotide 2'-O-methylation.
AB  - Archaeal box C/D sRNAs guide the 2'-O-methylation of target nucleotides using
      both terminal box C/D and internal C'/D' RNP complexes. In vitro assembly of a
      catalytically active Methanocaldococcus jannaschii sR8 box C/D RNP provides a
      model complex to determine those structural features of the guide:target RNA
      duplex important for sRNA-guided nucleotide methylation. Watson-Crick pairing of
      guide and target nucleotides was found to be essential for methylation, and
      mismatched bases within the guide:target RNA duplex also disrupted nucleotide
      modification. However, dependence upon Watson-Crick base-paired guide:target
      nucleotides for methylation was compromised in elevated Mg(2+) concentrations
      where mismatched target nucleotides were modified. Nucleotide methylation
      required that the guide:target duplex consist of an RNA:RNA duplex as a target
      ribonucleotide within a guide RNA:target DNA duplex that was not methylated.
      Interestingly, D and D' target RNAs exhibited different levels of methylation
      when deoxynucleotides were inserted into the target RNA or when target
      methylation was carried out in elevated Mg(2+) concentrations. These observations
      suggested that unique structural features of the box C/D and C'/D' RNPs
      differentially affect their respective methylation capabilities. The ability of
      the sR8 box C/D sRNP to methylate target nucleotides positioned within highly
      structured RNA hairpins suggested that the sRNP can facilitate unwinding of
      double-stranded target RNAs. Finally, increasing target RNA length to extend
      beyond those nucleotides that base pair with the sRNA guide sequence
      significantly increased sRNP turnover and thus nucleotide methylation. This
      suggests that target RNA interaction with the sRNP core proteins is also
      important for box C/D sRNP-guided nucleotide methylation.

PMID- 17438124
TI  - Structural differences within the loop E motif imply alternative mechanisms of
      viroid processing.
AB  - Viroids replicate via a rolling circle mechanism, and cleavage/ligation requires
      extensive rearrangement of the highly base-paired native structure. For Potato
      spindle tuber viroid (PSTVd), the switch from cleavage to ligation is driven by
      the change from a multibranched tetraloop structure to a loop E conformation.
      Here we present evidence that processing of Citrus viroid III (CVd-III), a member
      of a related group of viroids that also replicate in the nucleus, may proceed via
      a distinct pathway. Chemical probing of PSTVd and CVd-III miniRNAs with DMS and
      CMCT revealed that the loop E motifs of these two viroids have quite different
      tertiary structures. As shown by temperature gradient gel electrophoresis, the
      presence of two likely Watson-Crick GC pairs results in a significant overall
      stabilization of the CVd-III loop E-like motif. Unlike PSTVd, the upper strand of
      the CVd-III loop E-like motif cannot fold into a GNRA tetraloop, and comparison
      of suboptimal structures indicates that the initial cleavage event could occur on
      the 5' side of the only GU wobble pair in a helix involving a nearby pair of
      inverted repeats. According to our model, rearrangement of 3' sequences into a
      hairpin stem containing an identical arrangement of GC, GU, and CG base pairs and
      a second cleavage event is followed by formation of loop E, which serves to align
      the 5' and 3' termini of the CVd-III monomer prior to ligation. Because ligation
      would occur within loop E itself, stabilization of this motif may be needed to
      hold the 5' and 3' termini of CVd-III in position for the host ligase.

PMID- 17438126
TI  - NF-kappaB regulation of YY1 inhibits skeletal myogenesis through transcriptional
      silencing of myofibrillar genes.
AB  - NF-kappaB signaling is implicated as an important regulator of skeletal muscle
      homeostasis, but the mechanisms by which this transcription factor contributes to
      muscle maturation and turnover remain unclear. To gain insight into these
      mechanisms, gene expression profiling was examined in C2C12 myoblasts devoid of
      NF-kappaB activity. Interestingly, even in proliferating myoblasts, the absence
      of NF-kappaB caused the pronounced induction of several myofibrillar genes,
      suggesting that NF-kappaB functions as a negative regulator of late-stage muscle
      differentiation. Although several myofibrillar promoters contain predicted NF
      kappaB binding sites, functional analysis using the troponin-I2 gene as a model
      revealed that NF-kappaB-mediated repression does not occur through direct DNA
      binding. In the search for an indirect mediator, the transcriptional repressor
      YinYang1 (YY1) was identified. While inducers of NF-kappaB stimulated YY1
      expression in multiple cell types, genetic ablation of the RelA/p65 subunit of NF
      kappaB in both cultured cells and adult skeletal muscle correlated with reduced
      YY1 transcripts and protein. NF-kappaB regulation of YY1 occurred at the
      transcriptional level, mediated by direct binding of the p50/p65 heterodimer
      complex to the YY1 promoter. Furthermore, YY1 was found associated with multiple
      myofibrillar promoters in C2C12 myoblasts containing NF-kappaB activity. Based on
      these results, we propose that NF-kappaB regulation of YY1 and transcriptional
      silencing of myofibrillar genes represent a new mechanism by which NF-kappaB
      functions in myoblasts to modulate skeletal muscle differentiation.

PMID- 17438127
TI  - Analysis of the assembly profiles for mitochondrial- and nuclear-DNA-encoded
      subunits into complex I.
AB  - Complex I of the respiratory chain is composed of at least 45 subunits that
      assemble together at the mitochondrial inner membrane. Defects in human complex I
      result in energy generation disorders and are also implicated in Parkinson's
      disease and altered apoptotic signaling. The assembly of this complex is poorly
      understood and is complicated by its large size and its regulation by two
      genomes, with seven subunits encoded by mitochondrial DNA (mtDNA) and the
      remainder encoded by nuclear genes. Here we analyzed the assembly of a number of
      mtDNA- and nuclear-gene-encoded subunits into complex I. We found that mtDNA
      encoded subunits first assemble into intermediate complexes and require
      significant chase times for their integration into the holoenzyme. In contrast, a
      set of newly imported nuclear-gene-encoded subunits integrate with preexisting
      complex I subunits to form intermediates and/or the fully assembly holoenzyme.
      One of the intermediate complexes represents a subassembly associated with the
      chaperone B17.2L. By using isolated patient mitochondria, we show that this
      subassembly is a productive intermediate in complex I assembly since import of
      the missing subunit restores complex I assembly. Our studies point to a mechanism
      of complex I biogenesis involving two complementary processes, (i) synthesis of
      mtDNA-encoded subunits to seed de novo assembly and (ii) exchange of preexisting
      subunits with newly imported ones to maintain complex I homeostasis. Subunit
      exchange may also act as an efficient mechanism to prevent the accumulation of
      oxidatively damaged subunits that would otherwise be detrimental to mitochondrial
      oxidative phosphorylation and have the potential to cause disease.

PMID- 17438128
TI  - Bcl-XL/Bax proteins direct the fate of embryonic cortical precursor cells.
AB  - In the developing mouse brain, the highest Bcl-X(L) expression is seen at the
      peak of neurogenesis, whereas the peak of Bax expression coincides with the
      astrogenic period. While such observations suggest an active role of the Bcl-2
      family proteins in the generation of neurons and astrocytes, no definitive
      demonstration has been provided to date. Using combinations of gain- and loss-of
      function assays in vivo and in vitro, we provide evidence for instructive roles
      of these proteins in neuronal and astrocytic fate specification. Specifically, in
      Bax knockout mice, astrocyte formation was decreased in the developing cortices.
      Overexpression of Bcl-X(L) and Bax in embryonic cortical precursors induced
      neural and astrocytic differentiation, respectively, while inhibitory RNAs led to
      the opposite results. Importantly, inhibition of caspase activity, dimerization,
      or mitochondrial localization of Bcl-X(L)/Bax proteins indicated that the
      differentiation effects of Bcl-X(L)/Bax are separable from their roles in cell
      survival and apoptosis. Lastly, we describe activation of intracellular signaling
      pathways and expression of basic helix-loop-helix transcriptional factors
      specific for the Bcl-2 protein-mediated differentiation.

PMID- 17438129
TI  - Osteoblast autonomous Pi regulation via Pit1 plays a role in bone mineralization.
AB  - The complex pathogenesis of mineralization defects seen in inherited and/or
      acquired hypophosphatemic disorders suggests that local inorganic phosphate
      (P(i)) regulation by osteoblasts may be a rate-limiting step in physiological
      bone mineralization. To test whether an osteoblast autonomous phosphate
      regulatory system regulates mineralization, we manipulated well-established in
      vivo and in vitro models to study mineralization stages separately from cellular
      proliferation/differentiation stages of osteogenesis. Foscarnet, an inhibitor of
      NaP(i) transport, blocked mineralization of osteoid formation in osteoblast
      cultures and local mineralization after injection over the calvariae of newborn
      rats. Mineralization was also down- and upregulated, respectively, with under-
      and overexpression of the type III NaP(i) transporter Pit1 in osteoblast
      cultures. Among molecules expressed in osteoblasts and known to be related to
      P(i) handling, stanniocalcin 1 was identified as an early response gene after
      foscarnet treatment; it was also regulated by extracellular P(i), and itself
      increased Pit1 accumulation in both osteoblast cultures and in vivo. These
      results provide new insights into the functional role of osteoblast autonomous
      P(i) handling in normal bone mineralization and the abnormalities seen in
      skeletal tissue in hypophosphatemic disorders.

PMID- 17438130
TI  - Peroxisome proliferator-activated receptor alpha regulates a microRNA-mediated
      signaling cascade responsible for hepatocellular proliferation.
AB  - Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) leads
      to hepatocellular proliferation and liver carcinomas. The early events mediating
      these effects are unknown. A novel mechanism by which PPARalpha regulates gene
      expression and hepatocellular proliferation was uncovered. MicroRNA (miRNA)
      expression profiling demonstrated that activated PPARalpha was a major regulator
      of hepatic miRNA expression. Of particular interest, let-7C, an miRNA important
      in cell growth, was inhibited following 4-h treatment and 2-week and 11-month
      sustained treatment with the potent PPARalpha agonist Wy-14,643 in wild-type
      mice. let-7C was shown to target c-myc via direct interaction with the 3'
      untranslated region of c-myc. The PPARalpha-mediated induction of c-myc via let
      7C subsequently increased expression of the oncogenic mir-17-92 cluster; these
      events did not occur in Pparalpha-null mice. Overexpression of let-7C decreased c
      myc and mir-17 and suppressed the growth of Hepa-1 cells. Furthermore, using the
      human PPARalpha-expressing mouse model, which is responsive to Wy-14,643 effects
      on beta-oxidation and serum triglycerides but resistant to hepatocellular
      proliferation and tumorigenesis, we demonstrated a critical role for let-7C in
      liver oncogenesis. Wy-14,643 treatment did not inhibit let-7C or induce c-myc and
      mir-17 expression. These observations reveal a let-7C signaling cascade critical
      for PPARalpha agonist-induced liver proliferation and tumorigenesis.

PMID- 17438131
TI  - Cytokine activation of p38 mitogen-activated protein kinase and apoptosis is
      opposed by alpha-4 targeting of protein phosphatase 2A for site-specific
      dephosphorylation of MEK3.
AB  - alpha-4 is an essential gene and is a dominant antiapoptotic factor in various
      tissues that is a regulatory subunit for type 2A protein phosphatases. A
      multiplexed phosphorylation site screen revealed that knockdown of alpha-4 by
      small interfering RNA (siRNA) increased p38 mitogen-activated protein kinase
      (MAPK) and c-Jun phosphorylation without changes in JNK or ERK. FLAG-alpha-4
      coprecipitated hemagglutinin-MEK3 plus endogenous protein phosphatase 2A (PP2A)
      and selectively enhanced dephosphorylation of Thr193, but not Ser189, in the
      activation loop of MEK3. Overexpression of alpha-4 suppressed p38 MAPK activation
      in response to tumor necrosis factor alpha (TNF-alpha). The alpha-4 dominant
      negative domain (DND) (residues 220 to 340) associated with MEK3, but not PP2A,
      and its overexpression sensitized cells to activation of p38 MAPK by TNF-alpha
      and interleukin-1beta, but not by ansiomycin or sorbitol. The response was
      diminished by nocodazole or by siRNA knockdown of the Opitz syndrome protein Mid1
      that binds alpha-4 to microtubules. Interference by alpha-4 DND or alpha-4 siRNA
      increased caspase 3/7 activation in response to TNF-alpha. Growth of transformed
      cells in soft agar was enhanced by alpha-4 and suppressed by alpha-4 DND. The
      results show that alpha-4 targets PP2A activity to MEK3 to suppress p38 MAPK
      activation by cytokines, thereby inhibiting apoptosis and anoikis.

PMID- 17438132
TI  - Microphthalmia transcription factor isoforms in mast cells and the heart.
AB  - The microphthalmia transcription factor (Mitf) is critical for the survival and
      differentiation of a variety of cell types. While on the transcript level it has
      been noted that melanocytes and cardiomyocytes express specific Mitf isoforms,
      mast cells express several isoforms, mainly Mitf-H and Mitf-MC, whose function
      has not been thoroughly investigated. We found that in mast cells the expression
      of the specific Mitf isoforms is dependent on physiological stimuli that cause a
      major shifting of promoter usage and internal splicing. For example, activation
      of the c-kit signaling pathway almost totally abolished one of the main splice
      isoforms. Since cardiomyocytes express only the Mitf-H isoform, they were an
      ideal system to determine this isoform's physiological role. We identified that
      the expression of myosin light-chain 1a (MLC-1a) is regulated by Mitf-H.
      Interestingly, the transactivation of MLC-1a by Mitf-H in cardiomyocytes is
      decreased by overexpression of the splice form with exon 6a. In conclusion, we
      found that there is physiological switching of Mitf isoforms and that the
      promoter context and the cell context have a combined influence on gene
      expression programs.

PMID- 17438133
TI  - cPGES/p23 is required for glucocorticoid receptor function and embryonic growth
      but not prostaglandin E2 synthesis.
AB  - A number of studies have identified cytosolic prostaglandin E(2) synthase
      (cPGES)/p23 as a cytoplasmic protein capable of metabolism of prostaglandin E(2)
      (PGE(2)) from the cyclooxygenase metabolite prostaglandin endoperoxide (PGH(2)).
      However, this protein has also been implicated in a number of other pathways,
      including stabilization of the glucocorticoid receptor (GR) complex. To define
      the importance of the functions assigned to this protein, mice lacking detectible
      cPGES/p23 expression were generated. cPGES/p23(-/-) pups die during the perinatal
      period and display retarded lung development reminiscent of the phenotype of GR
      deficient neonates. Furthermore, GR-sensitive gluconeogenic enzymes are not
      induced in the prenatal period. However, unlike GR-deficient embryos, cPGES/p23(
      /-) embryos are small and a proliferation defect is observed in cPGES/p23(-/-)
      fibroblasts. Analysis of arachidonic acid metabolites in embryonic tissues and
      primary fibroblasts failed to support a function for this protein in PGE(2)
      biosynthesis. Thus, while the growth retardation of the cPGES/p23(-/-) pups and
      decreased proliferation of primary fibroblasts identify functions for this
      protein in addition to GR stabilization, it is unlikely that these functions
      include metabolism of PGH(2) to PGE(2).

PMID- 17438134
TI  - Constitutively activated Stat3 induces tumorigenesis and enhances cell motility
      of prostate epithelial cells through integrin beta 6.
AB  - The persistent activation of signal transducer and activator of transcription 3
      (Stat3) is a common feature of prostate cancer. However, little is known about
      the Stat3 targets that may mediate prostate tumorigenesis. The introduction of an
      activating mutant form of Stat3 (Stat3-C) into immortalized prostate epithelial
      cells resulted in tumorigenesis. Stat3-C-expressing cells had decreased E
      cadherin levels, increased numbers of lamellipodia and stress fibers, and
      enhanced migratory capacities compared to vector control-expressing cells, with a
      concomitant increase in the expression of integrin beta6 and its ligand,
      fibronectin (FN). Exogenously added FN increased cellular migration, with a
      concomitant loss of E-cadherin expression. The blockade of integrin alphavbeta6
      in Stat3-C-expressing cells inhibited migration, increased E-cadherin levels, and
      reduced colony formation in soft agar. These results demonstrate the sufficiency
      of constitutively activated Stat3 in mediating prostate tumorigenesis and
      identify novel Stat3 targets that are involved in promoting cell migration and
      transformation.

PMID- 17438135
TI  - Dissecting molecular steps in chromatin domain activation during hematopoietic
      differentiation.
AB  - GATA factors orchestrate hematopoiesis via multistep transcriptional mechanisms,
      but the interrelationships and importance of individual steps are poorly
      understood. Using complementation analysis with GATA-1-null cells and mice
      containing a hypomorphic allele of the chromatin remodeler BRG1, we dissected the
      pathway from GATA-1 binding to cofactor recruitment, chromatin loop formation,
      and transcriptional activation. Analysis of GATA-1-mediated activation of the
      beta-globin locus, in which GATA-1 assembles dispersed complexes at the promoters
      and the distal locus control region (LCR), revealed molecular intermediates,
      including GATA-1-independent and GATA-1-containing LCR subcomplexes, both
      defective in promoting loop formation. An additional intermediate consisted of an
      apparently normal LCR complex and a promoter complex with reduced levels of total
      RNA polymerase II (Pol II) and Pol II phosphorylated at serine 5 of the carboxy
      terminal domain. Reduced BRG1 activity solely compromised Pol II and serine 5
      phosphorylated Pol II occupancy at the promoter, phenocopying the LCR-deleted
      mouse. These studies defined a hierarchical order of GATA-1-triggered events at a
      complex locus and establish a novel mechanism of long-range gene regulation.

PMID- 17438136
TI  - Spreds are essential for embryonic lymphangiogenesis by regulating vascular
      endothelial growth factor receptor 3 signaling.
AB  - Spred/Sprouty family proteins negatively regulate growth factor-induced ERK
      activation. Although the individual physiological roles of Spred-1 and Spred-2
      have been investigated using gene-disrupted mice, the overlapping functions of
      Spred-1 and Spred-2 have not been clarified. Here, we demonstrate that the
      deletion of both Spred-1 and Spred-2 resulted in embryonic lethality at embryonic
      days 12.5 to 15.5 with marked subcutaneous hemorrhage, edema, and dilated
      lymphatic vessels filled with erythrocytes. This phenotype resembled that of Syk(
      /-) and SLP-76(-/-) mice with defects in the separation of lymphatic vessels from
      blood vessels. The number of LYVE-1-positive lymphatic vessels and lymphatic
      endothelial cells increased markedly in Spred-1/2-deficient embryos compared with
      WT embryos, while the number of blood vessels was not different. Ex vivo colony
      assay revealed that Spred-1/2 suppressed lymphatic endothelial cell proliferation
      and/or differentiation. In cultured cells, the overexpression of Spred-1 or Spred
      2 strongly suppressed vascular endothelial growth factor-C (VEGF-C)/VEGF receptor
      (VEGFR)-3-mediated ERK activation, while Spred-1/2-deficient cells were extremely
      sensitive to VEGFR-3 signaling. These data suggest that Spreds play an important
      role in lymphatic vessel development by negatively regulating VEGF-C/VEGFR-3
      signaling.

PMID- 17438137
TI  - MLN8054, a small-molecule inhibitor of Aurora A, causes spindle pole and
      chromosome congression defects leading to aneuploidy.
AB  - Aurora A kinase plays an essential role in the proper assembly and function of
      the mitotic spindle, as its perturbation causes defects in centrosome separation,
      spindle pole organization, and chromosome congression. Moreover, Aurora A
      disruption leads to cell death via a mechanism that involves aneuploidy
      generation. However, the link between the immediate functional consequences of
      Aurora A inhibition and the development of aneuploidy is not clearly defined. In
      this study, we delineate the sequence of events that lead to aneuploidy following
      Aurora A inhibition using MLN8054, a selective Aurora A small-molecule inhibitor.
      Human tumor cells treated with MLN8054 show a high incidence of abnormal mitotic
      spindles, often with unseparated centrosomes. Although these spindle defects
      result in mitotic delays, cells ultimately divide at a frequency near that of
      untreated cells. We show that many of the spindles in the dividing cells are
      bipolar, although they lack centrosomes at one or more spindle poles. MLN8054
      treated cells frequently show alignment defects during metaphase, lagging
      chromosomes in anaphase, and chromatin bridges during telophase. Consistent with
      the chromosome segregation defects, cells treated with MLN8054 develop aneuploidy
      over time. Taken together, these results suggest that Aurora A inhibition kills
      tumor cells through the development of deleterious aneuploidy.

PMID- 17438138
TI  - Proteasome activity modulates chromatin modifications and RNA polymerase II
      phosphorylation to enhance glucocorticoid receptor-mediated transcription.
AB  - The 26S proteasome modulates steroid hormone receptor-dependent gene
      transcription at least in part by regulating turnover and recycling of
      receptor/transcriptional DNA complexes, thereby ensuring continued hormone
      response. For the glucocorticoid receptor (GR), inhibition of proteasome-mediated
      proteolysis or RNA interference-mediated depletion of specific proteasome
      subunits results in an increase in gene expression. To facilitate transcription,
      proteasome inhibition alters at least two features associated with modification
      of chromatin architecture and gene transcription. First, proteasome inhibition
      increases trimethyl histone H3K4 levels with a corresponding accumulation of this
      modification on GR-regulated promoters in vivo. Secondly, global levels of
      phosphorylated RNA polymerase II (Pol II) increase, together with hormone
      dependent association of the phosphorylated Pol II, with the promoter and the
      body of the activated gene. We propose that apart from modulating receptor
      turnover, the proteasome directly influences both the transcription machinery and
      chromatin structure, factors integral to nuclear receptor-regulated gene
      transcription.

PMID- 17438139
TI  - Synaptic scaffolding molecule alpha is a scaffold to mediate N-methyl-D-aspartate
      receptor-dependent RhoA activation in dendrites.
AB  - Synaptic scaffolding molecule (S-SCAM) interacts with a wide variety of molecules
      at excitatory and inhibitory synapses. It comprises three alternative splicing
      variants, S-SCAMalpha, -beta, and -gamma. We generated mutant mice lacking
      specifically S-SCAMalpha. S-SCAMalpha-deficient mice breathe and feed normally
      but die within 24 h after birth. Primary cultured hippocampal neurons from mutant
      mice have abnormally elongated dendritic spines. Exogenously expressed S
      SCAMalpha corrects this abnormal morphology, while S-SCAMbeta and -gamma have no
      effect. Active RhoA decreases in cortical neurons from mutant mice.
      Constitutively active RhoA and ROCKII shift the length of dendritic spines toward
      the normal level, whereas ROCK inhibitor (Y27632) blocks the effect by S
      SCAMalpha. S-SCAMalpha fails to correct the abnormal spine morphology under the
      treatment of N-methyl-d-aspartate (NMDA) receptor inhibitor (AP-5),
      Ca(2+)/calmodulin kinase inhibitor (KN-62), or tyrosine kinase inhibitor (PP2).
      NMDA treatment increases active RhoA in dendrites in wild-type hippocampal
      neurons, but not in mutant neurons. The ectopic expression of S-SCAMalpha, but
      not -beta, recovers the NMDA-responsive accumulation of active RhoA in dendrites.
      Phosphorylation of extracellular signal-regulated kinase 1/2 and Akt and calcium
      influx in response to NMDA are not impaired in mutant neurons. These data
      indicate that S-SCAMalpha is a scaffold required to activate RhoA protein in
      response to NMDA receptor signaling in dendrites.

PMID- 17438140
TI  - Viable mice with compound mutations in the Wnt/Dvl pathway antagonists nkd1 and
      nkd2.
AB  - Gradients of Wnt/beta-catenin signaling coordinate development and physiological
      homeostasis in metazoan animals. Proper embryonic development of the fruit fly
      Drosophila melanogaster requires the Naked cuticle (Nkd) protein to attenuate a
      gradient of Wnt/beta-catenin signaling across each segmental anlage. Nkd inhibits
      Wnt signaling by binding the intracellular protein Dishevelled (Dsh). Mice and
      humans have two nkd homologs, nkd1 and nkd2, whose encoded proteins can bind Dsh
      homologs (the Dvl proteins) and inhibit Wnt signaling. To determine whether nkd
      genes are necessary for murine development, we replaced nkd exons that encode Dvl
      binding sequences with IRES-lacZ/neomycin cassettes. Mutants homozygous for each
      nkd(lacZ) allele are viable with slightly reduced mean litter sizes.
      Surprisingly, double-knockout mice are viable, with subtle alterations in cranial
      bone morphology that are reminiscent of mutation in another Wnt/beta-catenin
      antagonist, axin2. Our data show that nkd function in the mouse is dispensable
      for embryonic development.

PMID- 17438141
TI  - Orphan glutamate receptor delta1 subunit required for high-frequency hearing.
AB  - The function of the orphan glutamate receptor delta subunits (GluRdelta1 and
      GluRdelta2) remains unclear. GluRdelta2 is expressed exclusively in the Purkinje
      cells of the cerebellum, and GluRdelta1 is prominently expressed in inner ear
      hair cells and neurons of the hippocampus. We found that mice lacking the
      GluRdelta1 protein displayed significant cochlear threshold shifts for
      frequencies of >16 kHz. These deficits correlated with a substantial loss of type
      IV spiral ligament fibrocytes and a significant reduction of endolymphatic
      potential in high-frequency cochlear regions. Vulnerability to acoustic injury
      was significantly enhanced; however, the efferent innervation of hair cells and
      the classic efferent inhibition of outer hair cells were unaffected. Hippocampal
      and vestibular morphology and function were normal. Our findings show that the
      orphan GluRdelta1 plays an essential role in high-frequency hearing and ionic
      homeostasis in the basal cochlea, and the locus encoding GluRdelta1 represents a
      candidate gene for congenital or acquired high-frequency hearing loss in humans.

PMID- 17438142
TI  - Toll and IMD pathways synergistically activate an innate immune response in
      Drosophila melanogaster.
AB  - The inducible expression of antimicrobial peptide genes in Drosophila
      melanogaster is regulated by the conserved Toll and peptidoglycan recognition
      protein LC/immune deficiency (PGRP-LC/IMD) signaling pathways. It has been
      proposed that the two pathways have independent functions and mediate the
      specificity of innate immune responses towards different microorganisms.
      Scattered evidence also suggests that some antimicrobial target genes can be
      activated by both Toll and IMD, albeit to different extents. This dual activation
      can be mediated by independent stimulation or by cross-regulation of the two
      pathways. We show in this report that the Toll and IMD pathways can interact
      synergistically, demonstrating that cross-regulation occurs. The presence of
      Spatzle (the Toll ligand) and gram-negative peptidoglycan (the PGRP-LC ligand)
      together caused synergistic activation of representative target genes of the two
      pathways, including Drosomycin, Diptericin, and AttacinA. Constitutive activation
      of Toll and PGRP-LC/IMD could mimic the synergistic stimulation. RNA interference
      assays and promoter analyses demonstrate that cooperation of different NF-kappaB
      related transcription factors mediates the synergy. These results illustrate how
      specific ligand binding by separate upstream pattern recognition receptors can be
      translated into a broad-spectrum host response, a hallmark of innate immunity.

PMID- 17438143
TI  - Ca2+ -dependent interaction of S100A1 with F1-ATPase leads to an increased ATP
      content in cardiomyocytes.
AB  - S100A1, a Ca(2+)-sensing protein of the EF-hand family that is expressed
      predominantly in cardiac muscle, plays a pivotal role in cardiac contractility in
      vitro and in vivo. It has recently been demonstrated that by restoring Ca(2+)
      homeostasis, S100A1 was able to rescue contractile dysfunction in failing rat
      hearts. Myocardial contractility is regulated not only by Ca(2+) homeostasis but
      also by energy metabolism, in particular the production of ATP. Here, we report a
      novel interaction of S100A1 with mitochondrial F(1)-ATPase, which affects F(1)
      ATPase activity and cellular ATP production. In particular, cardiomyocytes that
      overexpress S100A1 exhibited a higher ATP content than control cells, whereas
      knockdown of S100A1 expression decreased ATP levels. In pull-down experiments, we
      identified the alpha- and beta-chain of F(1)-ATPase to interact with S100A1 in a
      Ca(2+)-dependent manner. The interaction was confirmed by colocalization studies
      of S100A1 and F(1)-ATPase and the analysis of the S100A1-F(1)-ATPase complex by
      gel filtration chromatography. The functional impact of this association is
      highlighted by an S100A1-mediated increase of F(1)-ATPase activity. Consistently,
      ATP synthase activity is reduced in cardiomyocytes from S100A1 knockout mice. Our
      data indicate that S100A1 might play a key role in cardiac energy metabolism.

PMID- 17438145
TI  - Astroglia-derived retinoic acid is a key factor in glia-induced neurogenesis.
AB  - Astroglial cells are essential components of the neurogenic niches within the
      central nervous system. Emerging evidence suggests that they are among the key
      regulators of postnatal neurogenesis. Although astrocytes have been demonstrated
      to possess the potential to instruct stem cells to adopt a neuronal fate, little
      is known about the nature of the glia-derived instructive signals. Here we
      propose that all-trans retinoic acid, one of the most powerful morphogenic
      molecules regulating neuronal cell fate commitment, may be one of the glia
      derived factors directing astroglia-induced neurogenesis. According to data
      obtained from several complementary approaches, we show that cultured astrocytes
      express the key enzyme mRNAs of retinoic acid biosynthesis and actively produce
      all-trans retinoic acid. We show that blockage of retinoic acid signaling by the
      pan-RAR antagonist AGN193109 prevents glia-induced neuron formation by
      noncommitted stem cells. Therefore, we provide strong in vitro evidence for
      retinoic acid action in astroglia-induced neuronal differentiation.

PMID- 17438144
TI  - Smad7 antagonizes transforming growth factor beta signaling in the nucleus by
      interfering with functional Smad-DNA complex formation.
AB  - Smad7 plays an essential role in the negative-feedback regulation of transforming
      growth factor beta (TGF-beta) signaling by inhibiting TGF-beta signaling at the
      receptor level. It can interfere with binding to type I receptors and thus
      activation of receptor-regulated Smads or recruit the E3 ubiquitin ligase Smurf
      to receptors and thus target them for degradation. Here, we report that Smad7 is
      predominantly localized in the nucleus of Hep3B cells. The targeted expression of
      Smad7 in the nucleus conferred superior inhibitory activity on TGF-beta
      signaling, as determined by reporter assay in mammalian cells and by its effect
      on zebrafish embryogenesis. Furthermore, Smad7 repressed Smad3/4-, Smad2/4-, and
      Smad1/4-enhanced reporter gene expression, indicating that Smad7 can function
      independently of type I receptors. An oligonucleotide precipitation assay
      revealed that Smad7 can specifically bind to the Smad-responsive element via its
      MH2 domain, and DNA-binding activity was further confirmed in vivo with the
      promoter of PAI-1, a TGF-beta target gene, by chromatin immunoprecipitation.
      Finally, we provide evidence that Smad7 disrupts the formation of the TGF-beta
      induced functional Smad-DNA complex. Our findings suggest that Smad7 inhibits TGF
      beta signaling in the nucleus by a novel mechanism.

PMID- 17438146
TI  - A1 adenosine receptor upregulation accompanies decreasing myocardial adenosine
      levels in mice with left ventricular dysfunction.
AB  - BACKGROUND: It is well known that adenosine levels are increased during ischemia
      and protect the heart during ischemia/reperfusion. However, less is known about
      the role of adenosine-adenosine receptor (AR) pathways in hearts with left
      ventricular dilation and dysfunction. Therefore, we assessed adenosine levels and
      selective AR expression in transgenic mice with left ventricular systolic
      dysfunction secondary to overexpression of tumor necrosis factor-alpha (TNF 1.6).
      METHODS AND RESULTS: Cardiac adenosine levels were reduced by 70% at 3 and 6
      weeks of age in TNF 1.6 mice. This change was accompanied by a 4-fold increase in
      the levels of A1-AR and a 50% reduction in the levels of A2A-AR. That the
      increase in A1-AR density was of physiological significance was shown by the fact
      that chronotropic responsiveness to the A1-AR selective agonist 2-chloro-N6
      cyclopentanyladenosine was enhanced in the TNF 1.6 mice. Similar changes in
      adenosine levels were found in 2 other models of heart failure, mice
      overexpressing calsequestrin and mice after chronic pressure overload, suggesting
      that the changes in adenosine-AR signaling were secondary to myocardial
      dysfunction rather than to TNF overexpression. CONCLUSIONS: Cardiac dysfunction
      secondary to the overexpression of TNF is associated with marked alterations in
      myocardial levels of adenosine and ARs. Modulation of the myocardial adenosine
      system and its signaling pathways may be a novel therapeutic target in patients
      with heart failure.

PMID- 17438147
TI  - Pathological correlates of late drug-eluting stent thrombosis: strut coverage as
      a marker of endothelialization.
AB  - BACKGROUND: Late stent thrombosis (LST) after Cypher and Taxus drug-eluting stent
      placement has emerged as a major concern. Although the clinical predictors of LST
      have been reported, specific morphological and histological correlates of LST
      remain unknown. METHODS AND RESULTS: From a registry totaling 81 human autopsies
      of drug-eluting stents, 46 (62 lesions) had a drug-eluting stent implanted >30
      days. We identified 28 lesions with thrombus and compared those with 34 of
      similar duration without thrombosis using computer-guided morphometric and
      histological analyses. LST was defined as an acute thrombus within a coronary
      artery stent in place >30 days. Multiple logistic generalized estimating
      equations modeling demonstrated that endothelialization was the best predictor of
      thrombosis. The morphometric parameter that best correlated with
      endothelialization was the ratio of uncovered to total stent struts per section.
      A univariable logistic generalized estimating equations model of occurrence of
      thrombus in a stent section versus ratio of uncovered to total stent struts per
      section demonstrated a marked increase in risk for LST as the number of uncovered
      struts increased. The odds ratio for thrombus in a stent with a ratio of
      uncovered to total stent struts per section >30% is 9.0 (95% CI, 3.5 to 22).
      CONCLUSIONS: The most powerful histological predictor of stent thrombosis was
      endothelial coverage. The best morphometric predictor of LST was the ratio of
      uncovered to total stent struts. Heterogeneity of healing is a common finding in
      drug-eluting stents with evidence of LST and demonstrates the importance of
      incomplete healing of the stented segment in the pathophysiology of LST.

PMID- 17438148
TI  - Targeting platelets in acute experimental stroke: impact of glycoprotein Ib, VI,
      and IIb/IIIa blockade on infarct size, functional outcome, and intracranial
      bleeding.
AB  - BACKGROUND: Ischemic stroke is a frequent and serious disease with limited
      treatment options. Platelets can adhere to hypoxic cerebral endothelial cells by
      binding of their glycoprotein (GP) Ib receptor to von Willebrand factor. Exposure
      of subendothelial matrix proteins further facilitates firm attachment of
      platelets to the vessel wall by binding of collagen to their GPVI receptor. In
      the present study, we addressed the pathogenic role of GPIb, GPVI, and the
      aggregation receptor GPIIb/IIIa in experimental stroke in mice. METHODS AND
      RESULTS: Complete blockade of GPIb alpha was achieved by intravenous injection of
      100 microg Fab fragments of the monoclonal antibody p0p/B to mice undergoing 1
      hour of transient middle cerebral artery occlusion. At 24 hours after transient
      middle cerebral artery occlusion, cerebral infarct volumes were assessed by 2,3,5
      triphenyltetrazolium chloride staining. In mice treated with anti-GPIb alpha Fab
      1 hour before middle cerebral artery occlusion, ischemic lesions were reduced to
      approximately 40% compared with controls (28.5+/-12.7 versus 73.9+/-17.4 mm3,
      respectively; P<0.001). Application of anti-GPIb alpha Fab 1 hour after middle
      cerebral artery occlusion likewise reduced brain infarct volumes (24.5+/-7.7 mm3;
      P<0.001) and improved the neurological status. Similarly, depletion of GPVI
      significantly diminished the infarct volume but to a lesser extent (49.4+/-19.1
      mm3; P<0.05). Importantly, the disruption of early steps of platelet activation
      was not accompanied by an increase in bleeding complications as revealed by
      serial magnetic resonance imaging. In contrast, blockade of the final common
      pathway of platelet aggregation with anti-GPIIb/IIIa F(ab)2 fragments had no
      positive effect on stroke size and functional outcome but increased the incidence
      of intracerebral hemorrhage and mortality after transient middle cerebral artery
      occlusion in a dose-dependent manner. CONCLUSIONS: Our data indicate that the
      selective blockade of key signaling pathways of platelet adhesion and aggregation
      has a different impact on stroke outcome and bleeding complications. Inhibition
      of early steps of platelet adhesion to the ischemic endothelium and the
      subendothelial matrix may offer a novel and safe treatment strategy in acute
      stroke.

PMID- 17438150
TI  - Phosphodiesterase 1 upregulation in pulmonary arterial hypertension: target for
      reverse-remodeling therapy.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a life-threatening disease,
      characterized by vascular smooth muscle cell hyperproliferation. The
      calcium/calmodulin-dependent phosphodiesterase 1 (PDE1) may play a major role in
      vascular smooth muscle cell proliferation. METHODS AND RESULTS: We investigated
      the expression of PDE1 in explanted lungs from idiopathic PAH patients and animal
      models of PAH and undertook therapeutic intervention studies in the animal
      models. Strong upregulation of PDE1C in pulmonary arterial vessels in the
      idiopathic PAH lungs compared with healthy donor lungs was noted on the mRNA
      level by laser-assisted vessel microdissection and on the protein level by
      immunohistochemistry. In chronically hypoxic mouse lungs and lungs from
      monocrotaline-injected rats, PDE1A upregulation was detected in the structurally
      remodeled arterial muscular layer. Long-term infusion of the PDE1 inhibitor 8
      methoxymethyl 3-isobutyl-1-methylxanthine in hypoxic mice and monocrotaline
      injected rats with fully established pulmonary hypertension reversed the
      pulmonary artery pressure elevation, structural remodeling of the lung
      vasculature (nonmuscularized versus partially muscularized versus fully
      muscularized small pulmonary arteries), and right heart hypertrophy. CONCLUSIONS:
      Strong upregulation of the PDE1 family in pulmonary artery smooth muscle cells is
      noted in human idiopathic PAH lungs and lungs from animal models of PAH.
      Inhibition of PDE1 reverses structural lung vascular remodeling and right heart
      hypertrophy in 2 animal models. The PDE1 family may thus offer a new target for
      therapeutic intervention in pulmonary hypertension.

PMID- 17438151
TI  - Poly(ADP-ribose) polymerase inhibition reduces atherosclerotic plaque size and
      promotes factors of plaque stability in apolipoprotein E-deficient mice: effects
      on macrophage recruitment, nuclear factor-kappaB nuclear translocation, and foam
      cell death.
AB  - BACKGROUND: Poly(ADP-ribose) polymerase (PARP) was suggested to play a role in
      endothelial dysfunction that is associated with a number of cardiovascular
      diseases. We hypothesized that PARP may play an important role in atherogenesis
      and that its inhibition may attenuate atherosclerotic plaque development in an
      experimental model of atherosclerosis. METHODS AND RESULTS: Using a mouse
      (apolipoprotein E [ApoE](-/-)) model of high-fat diet-induced atherosclerosis, we
      demonstrate an association between cell death and oxidative stress-associated DNA
      damage and PARP activation within atherosclerotic plaques. PARP inhibition by
      thieno[2,3-c]isoquinolin-5-one reduced plaque number and size and altered
      structural composition of plaques in these animals without affecting sera lipid
      contents. These results were corroborated genetically with the use of ApoE(-/-)
      mice that are heterozygous for PARP-1. PARP inhibition promoted an increase in
      collagen content, potentially through an increase in tissue inhibitor of
      metalloproteinase-2, and transmigration of smooth muscle cells to intima of
      atherosclerotic plaques as well as a decrease in monocyte chemotactic protein-1
      production, all of which are markers of plaque stability. In PARP-1(-/-)
      macrophages, monocyte chemotactic protein-1 expression was severely inhibited
      because of a defective nuclear factor-kappaB nuclear translocation in response to
      lipopolysaccharide. Furthermore, PARP-1 gene deletion not only conferred
      protection to foam cells against H2O2-induced death but also switched the mode of
      death from necrosis to apoptosis. CONCLUSIONS: Our results suggest that PARP
      inhibition interferes with plaque development and may promote plaque stability,
      possibly through a reduction in inflammatory factors and cellular changes related
      to plaque dynamics. PARP inhibition may prove beneficial for the treatment of
      atherosclerosis.

PMID- 17438152
TI  - Direct intramyocardial but not intracoronary injection of bone marrow cells
      induces ventricular arrhythmias in a rat chronic ischemic heart failure model.
AB  - BACKGROUND: Therapeutic efficacy of bone marrow (BM) cell injection for treating
      ischemic chronic heart failure has not been established. In addition,
      experimental data are lacking on arrhythmia occurrence after BM cell injection.
      We hypothesized that therapeutic efficacy and arrhythmia occurrence induced by BM
      cell injection may be affected by the cell delivery route. METHODS AND RESULTS:
      Three weeks after left coronary artery ligation, wild-type female rats were
      injected with 1x10(7) mononuclear BM cells derived from green fluorescent protein
      transgenic male rats through either a direct intramyocardial or a retrograde
      intracoronary route. Both intramyocardial and intracoronary injection of BM cells
      demonstrated similar improvement in left ventricular ejection fraction measured
      by echocardiography and a similar graft size analyzed by real-time polymerase
      chain reaction for the Y chromosome-specific Sry gene. Noticeably,
      intramyocardial injection of BM cells induced frequent ventricular premature
      contractions (108+/-73 per hour at 7 days after BM cell injection), including
      multiform, consecutive ventricular premature contractions and ventricular
      tachycardia for the initial 14 days; intracoronary injection of BM cells and
      intramyocardial injection of phosphate-buffered saline rarely induced
      arrhythmias. Immunohistochemistry demonstrated that intramyocardial BM cell
      injection formed distinct cell clusters containing donor-derived cells and
      accumulated host-derived inflammatory cells in the infarct border zone, whereas
      intracoronary BM cell injection provided more homogeneous donor cell
      dissemination with less inflammation and without disrupting the native myocardial
      structure. CONCLUSIONS: BM cell injection is able to improve cardiac function in
      ischemic chronic heart failure but has a risk of arrhythmia occurrence when the
      intramyocardial route is used. Such arrhythmias may be prevented by using the
      intracoronary route.

PMID- 17438153
TI  - Heredity of endothelin secretion: human twin studies reveal the influence of
      polymorphism at the chromogranin A locus, a novel determinant of endothelial
      function.
AB  - BACKGROUND: Endothelial dysfunction predisposes to vascular injury in association
      with hypertension. Endothelin (ET-1) is a potent vasoactive peptide that is
      synthesized and released by the vascular endothelium and is a marker of
      endothelial function. Chromogranin A (CHGA) regulates the storage and release of
      catecholamines and may have direct actions on the microvasculature. CHGA, a
      candidate gene for intermediate phenotypes that contribute to hypertension, shows
      a pattern of single nucleotide polymorphism variations that alter the expression
      and function of this gene both in vivo and in vitro. METHODS AND RESULTS: In a
      study of twins (n=238 pairs), plasma ET-1 was 58+/-5% (P<0.0001) heritable.
      Plasma ET-1 was both correlated and associated with chromogranin fragment levels,
      and the 2 were influenced by shared genetic determination (pleiotropy [rhoG]; for
      the CHGA precursor, rhoG=0.318+/-0.105; P=0.0032). We therefore hypothesized that
      variation in the CHGA gene may influence ET-1 secretion. Carriers of the CHGA
      promoter -988G, -462A, and -89A minor alleles showed significantly higher mean
      plasma ET-1 than their major allele homozygote counterparts (P=0.02, P=0.006,
      P=0.03, respectively). Analysis of a linkage disequilibrium block that spans
      these 3 single nucleotide polymorphisms showed a significant association between
      the GATACA haplotype and plasma ET-1 (P=0.0075). In cultured human umbilical vein
      endothelial cells, CHGA caused dose-dependent secretion of ET-1 over a brief (<1
      hour) time course at relatively low concentrations of CHGA (10 to 100 nmol/L)
      with a threshold concentration (10 nmol/L) in the range found circulating in
      humans in vivo. CONCLUSIONS: These results suggest that common, heritable
      variation in expression of the human CHGA gene influences endothelial ET-1
      secretion in vivo, explained by a CHGA stimulus/ET-1 secretion coupling in
      endothelial cells in vitro. The findings document a previously unsuspected
      interaction between the sympathochromaffin system and the endothelium and suggest
      novel genetic and cell biological approaches to the prediction, diagnosis, and
      mechanism of endothelial dysfunction in human disease.

PMID- 17438154
TI  - Catecholamine release-inhibitory peptide catestatin (chromogranin A(352-372)):
      naturally occurring amino acid variant Gly364Ser causes profound changes in human
      autonomic activity and alters risk for hypertension.
AB  - BACKGROUND: Chromogranin A, coreleased with catecholamines by exocytosis, is
      cleaved to the catecholamine release-inhibitory fragment catestatin. We
      identified a natural nonsynonymous variant of catestatin, Gly364Ser, that alters
      human autonomic function and blood pressure. METHODS AND RESULTS: Gly364Ser
      heterozygotes and controls underwent physiological and biochemical phenotyping,
      including catecholamine production, chromogranin A precursor, and its catestatin
      product. Case-control studies replicated effects of the gene on blood pressure in
      the population. Gly364Ser displayed diminished inhibition of catecholamine
      secretion from cultured neurons. Gly/Ser heterozygotes displayed increased
      baroreceptor slope during upward deflections (by approximately 47%) and downward
      deflections (by approximately 44%), increased cardiac parasympathetic index (by
      approximately 2.4-fold), and decreased cardiac sympathetic index (by
      approximately 26%). Renal norepinephrine excretion was diminished by
      approximately 26% and epinephrine excretion by approximately 34% in Gly/Ser
      heterozygotes. The coalescent dated emergence of the variant to approximately
      70,000 years ago. Gly364Ser was in linkage disequilibrium with 1 major
      Chromogranin A promoter haplotype, although promoter haplotypes did not predict
      autonomic phenotypes. The 364Ser variant was associated with lower diastolic
      blood pressure in 2 independent/confirmatory groups of patients with
      hypertension; genotype groups differed by approximately 5 to 6 mm Hg, and the
      polymorphism accounted for approximately 1.8% of population diastolic blood
      pressure variance, although a significant gene-by-sex interaction existed, with
      an enhanced effect in men. CONCLUSIONS: The catestatin Gly364Ser variant causes
      profound changes in human autonomic activity, both parasympathetic and
      sympathetic, and seems to reduce risk of developing hypertension, especially in
      men. A model for catestatin action in the baroreceptor center of the nucleus of
      the tractus solitarius accounts for these actions.

PMID- 17438155
TI  - Images in cardiovascular medicine. Neonatal tuberous sclerosis and multiple
      cardiac arrhythmias.

PMID- 17438156
TI  - Images in cardiovascular medicine. Definitive diagnosis of pulmonary artery sling
      in a critically ill infant with high-resolution computed tomography.

PMID- 17438157
TI  - Images in cardiovascular medicine. Percutaneous closure of a false aneurysm of
      the right ventricle in a congenital heart disease patient.

PMID- 17438158
TI  - Letter by Padfield et al regarding article, "Randomized trial of atorvastatin for
      reduction of postoperative atrial fibrillation in patients undergoing cardiac
      surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of Myocardial
      Dysrhythmia After Cardiac Surgery) study".

PMID- 17438159
TI  - Letter by Shroff and Orlandi regarding article, "Randomized trial of atorvastatin
      for reduction of postoperative atrial fibrillation in patients undergoing cardiac
      surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of Myocardial
      Dysrhythmia After Cardiac Surgery) study".

PMID- 17438160
TI  - Viewpoint: Obesity in Europe. Interview by Barry Shurlock.

PMID- 17438161
TI  - Brugada syndrome in children: don't ask, don't tell?

PMID- 17438162
TI  - The obese hypertensive: the weight of evidence against beta-blockers.

PMID- 17438163
TI  - Molecular magnetic resonance imaging in cardiovascular medicine.

PMID- 17438164
TI  - Young academic surgeons participating in laboratory and translational research.

PMID- 17438165
TI  - Gender and the surgical workforce.

PMID- 17438166
TI  - Predicting future staffing needs at teaching hospitals: use of an analytical
      program with multiple variables.
AB  - OBJECTIVE: To develop a model to predict future staffing for the surgery service
      at a teaching hospital. SETTING: Tertiary hospital. INTERVENTIONS: A computer
      model with potential future variables was constructed. Some of the variables were
      distribution of resident staff, fellows, and physician extenders; salary/wages;
      work hours; educational value of rotations; work units, inpatient wards, and
      clinics; future volume growth; and efficiency savings. Outcomes Number of staff
      to be hired, staffing expense, and educational impact. RESULTS: On a busy general
      surgery service, we estimated the impact of changes in resident work hours,
      service growth, and workflow efficiency in the next 5 years. Projecting a
      reduction in resident duty hours to 60 hours per week will require the hiring of
      10 physician assistants at a cost of $1 134 000, a cost that is increased by $441
      000 when hiring hospitalists instead. Implementing a day of didactic and
      simulator time (10 hours) will further increase the costs by $568 000. A 10%
      improvement in the efficiency of floor care, as might be gained by advanced
      information technology capability or by regionalization of patients, can mitigate
      these expenses by as much as 21%. On the other hand, a modest annual growth of 2%
      will increase the costs by $715 000 to $2 417 000. CONCLUSIONS: To simply replace
      residents with alternative providers requires large amounts of human and fiscal
      capital. The potential for simple efficiencies to mitigate some of this expense
      suggests that traditional patterns of care in teaching hospitals will have to
      change in response to educational mandates.

PMID- 17438167
TI  - Midlevel practitioner workforce analysis at a university-affiliated teaching
      hospital.
AB  - OBJECTIVE: To quantify midlevel practitioner (MLP) staffing requirements based on
      the volume and complexity of patient care and the duty-hour constraints of the
      Accreditation Council for Graduate Medical Education 80-hour workweek. DESIGN:
      Data extracted from Eclipsys Sunrise Decision Support Manager, the hospital
      financial budget, and census reports; and MLP, resident, and subspecialty fellow
      clinical, operative, and on-call schedules, and educational curriculum. Fiscal
      year 2005 patient census and hours of required care were defined by attending
      physician service and/or patient care location. Volume of patient care activity
      for MLPs, residents, and subspecialty fellows were established by verified self
      reporting methodology. SETTING: Urban teaching hospital with 867 beds, of which
      116 are surgical beds (which include 36 intensive care unit beds and 12 step-down
      beds). PARTICIPANTS: Attending physicians, MLPs, residents, and subspecialty
      fellows. MAIN OUTCOME MEASURES: Coverage index (available staffing hours
      [residents, subspecialty fellows, and MLPs] divided by the clinical coverage
      schedule), and the workload staffing efficiency index (number of clinical hours
      of patient care activities divided by the hours of available staff for a specific
      clinical service). RESULTS: The workload staffing efficiency index and the
      coverage index identified 4 services that benefited from the addition of new
      MLPs. CONCLUSION: We developed a quantitative MLP staffing methodology based on
      patient volume and the type and complexity of direct and indirect patient care
      activities, encompassing the roles and availability of residents, subspecialty
      fellows, and MLPs.

PMID- 17438168
TI  - Sonographic hematoma-guided vs wire-localized lumpectomy for breast cancer: a
      comparison of margins and volume of resection.
AB  - HYPOTHESIS: Sonographic hematoma-guided (SHG) lumpectomy achieves better margin
      clearance with a smaller volume of resection compared with wire-localized (WL)
      lumpectomy. DESIGN: Retrospective study. SETTING: University Comprehensive Breast
      Center. PATIENTS: Consecutive patients treated over 6 months at the breast center
      with stereotactic biopsy-proven cancers that were not visualized on
      ultrasonography. The SHG and WL techniques were compared. MAIN OUTCOME MEASURES:
      The matching variables were age, mammographic abnormality, tumor size and type,
      and lymph node status. The outcome variables were the closest margin of
      resection, volume of resection, resection index (resection volume divided by
      tumor volume), and rate of margin revision. RESULTS: Twenty-nine patients had SHG
      lumpectomy and 34 had WL lumpectomy. The SHG and WL groups were similar in age,
      mammographic abnormality, tumor size and type, and lymph node status. The median
      (interquartile range) closest margin was 5.0 (5-8) mm in the SHG group vs 3.5 (1
      7) mm in the WL group (P = .01). The median (interquartile range) resection
      volume was 85.0 (60-128) cm(3) in the SHG group vs 143.4 (54-229) cm(3) in the WL
      group (P = .048). The median (interquartile range) resection index was 77.1 (51
      220) in the SHG group vs 315.9 (89-3025) in the WL group (P = .003). The margin
      was revised in 1 (3.4%) of the patients who underwent SHG lumpectomy vs 5 (14.7%)
      of the patients who underwent WL lumpectomy (P = .20). CONCLUSIONS: Sonographic
      hematoma-guided lumpectomy is superior to WL lumpectomy in obtaining adequate
      margins while minimizing the volume of resection.

PMID- 17438169
TI  - Evolving patterns in the detection and outcomes of pancreatic neuroendocrine
      neoplasms: the Massachusetts General Hospital experience from 1977 to 2005.
AB  - OBJECTIVE: To assess changing patterns in the detection and outcomes of
      pancreatic neuroendocrine neoplasms (PNENs). DESIGN: Retrospective review from
      May 21, 1977, through September 16, 2005. SETTING: Massachusetts General
      Hospital, a tertiary care center. PATIENTS: We evaluated 168 patients (51% male;
      mean age, 56 years) who underwent surgery for histologically confirmed PNENs.
      MAIN OUTCOME MEASURES: Surgical outcomes, survival, and changes in presentation
      of PNENs in 2 time groups: 1977-1999 (77 patients) and 2000-2005 (91 patients).
      RESULTS: Ninety-eight patients (58.3%) had nonfunctioning PNENs, 86 of which were
      incidental. Insulinomas were the most common type of functional neoplasm (33.3%),
      followed by gastrinomas and glucagonomas; 12 patients (7.1%) had multiple
      endocrine neoplasia type 1. Of the neoplasms, 107 (63.7%) were located in the
      pancreatic body or tail. A pancreaticoduodenectomy was performed in 37 patients
      (22.0%), distal pancreatectomy was done in 88 (52.4%), and the rest had either
      middle segment pancreatectomy or enucleation. There were no operative deaths. We
      classified 76.8% of neoplasms as benign; of those classified as malignant, 25.6%
      had liver metastases. Of the patients, 10.1% received adjuvant therapy. Complete
      follow up was available in 90.5% of patients (mean, 63.3 months). Five- and 10
      year actuarial survival rates were 77% and 62%, respectively. Incidentally
      discovered nonfunctioning neoplasms were significantly more frequent in the last
      5 years (60.4% vs 40.3%; P = .007), with a trend toward smaller neoplasms (mean,
      4.2 cm vs 5.6 cm; P = .19) and lesser likelihood of malignancy (21.8% vs 40.0%; P
      = .08). CONCLUSIONS: We report a large single-center experience with PNENs.
      Increasing numbers of PNENs are being resected, largely owing to the incidental
      detection of nonfunctioning neoplasms. This may lead to the treatment of smaller
      and less malignant neoplasms.

PMID- 17438170
TI  - Enhancing compliance with Medicare guidelines for surgical infection prevention:
      experience with a cross-disciplinary quality improvement team.
AB  - HYPOTHESIS: The Center for Medicare and Medicaid Services instituted standardized
      reporting of measures aimed at surgical infection prevention (SIP). The
      complexity and number of medical personnel involved in antibiotic administration
      requires multiple disciplines to successfully improve compliance. DESIGN: Survey
      study. SETTING: Tertiary care university hospital. PATIENTS: All patients
      undergoing the following operations from July 2004 through December 2005 were
      monitored for compliance with SIP: (1) coronary artery bypass graft, (2) other
      cardiac, (3) vascular, (4) hysterectomy, (5) colon resection, (6) hip
      arthroplasty, and (7) knee arthroplasty. INTERVENTION: A team including a
      surgeon, an anesthesiologist, nurses (preoperative, operating room, and floor), a
      pharmacist, a hospital infection control committee member, and quality
      improvement and operations specialists was created in July 2004. Hospital
      guidelines for SIP were defined, personnel roles defined and processes
      standardized, and communication/education for health care professionals was
      enhanced. MAIN OUTCOME MEASURES: Compliance with 3 SIP measures over 3
      consecutive periods of 6 months each: (1) percentage of patients receiving
      antibiotics within 1 hour of incision, (2) percentage of patients with
      appropriately selected antibiotics, and (3) percentage of patients with
      antibiotics discontinued within 24 hours of operation end time. RESULTS: One
      thousand seventy-two patients were monitored. Measure 1 compliance improved from
      72.25% to 83.78% (P<.001, Cochran-Armitage trend test); improvement or high
      performance (>90% compliance) was demonstrated in 5 of 7 services. Measure 2
      compliance remained uniformly high (approximately 98%). Measure 3 compliance
      improved from 54.5% to 87.16% (P<.001); improvement was seen in 5 of 7 services.
      CONCLUSIONS: The clearly defined roles of a cross-disciplinary team and the
      process improvements discussed in this article can easily be implemented in other
      institutions. These elements were integral to our success in improving the timely
      delivery and discontinuation of prophylactic surgical antibiotics.

PMID- 17438171
TI  - Initial experience with laparoscopic inferior epigastric vessel ligation for
      delayed transverse rectus abdominus musculocutaneous flap breast reconstruction.
AB  - HYPOTHESIS: Transverse rectus abdominus musculocutaneous (TRAM) flap breast
      reconstruction provides excellent cosmetic results. Pedicle flap viability is
      greatly enhanced by prereconstruction inferior epigastric vessel ligation, which
      encourages collateral arterial flow (delayed TRAM). We report our initial
      experience with laparoscopic inferior epigastric vessel ligation. DESIGN:
      Prospective case series. SETTING: Tertiary academic center. PATIENTS: Female
      patients with breast cancer who chose pedicle TRAM reconstruction. INTERVENTIONS:
      Vessel ligations were performed 7 to 14 days prior to reconstruction. Abdominal
      access was achieved with a 3-mm umbilical trocar. A 5-mm trocar was placed
      lateral to the rectus sheath in the right lower quadrant. Five-millimeter Teflon
      clips were used to ligate the vessels near their origin. MAIN OUTCOME MEASURES:
      Complications of surgery and subsequent flap viability. RESULTS: From January
      2001 to July 2006, 130 patients had laparoscopic inferior epigastric vessel
      ligation, of whom 123 patients had bilateral ligation. Additional procedures in
      conjunction with vessel ligation were performed in 38 patients (sentinel node
      biopsy [27], bilateral oophorectomy [7], liver biopsy [2], breast biopsy [1], and
      Nissen fundoplication [1]). Median operative time for those patients undergoing
      ligation only was 32.6 minutes (range, 14-121 minutes). The inferior epigastric
      vessels were not identified in 2 patients. Metastatic breast cancer involving the
      liver was found in 1 patient. There were no conversions or complications.
      Subsequent TRAM flap viability was excellent in most cases, with 1 complete flap
      necrosis in a high-risk, morbidly obese patient. CONCLUSION: Laparoscopic
      inferior epigastric vessel ligation for delayed TRAM flap breast reconstruction
      is a safe, effective procedure.

PMID- 17438172
TI  - Surgeon profiling: a key to optimum operating room use.
AB  - HYPOTHESIS: A high-efficiency Pod, composed of 3 parallel-processing operating
      rooms (ORs) and a dedicated 3-bed miniature postanesthesia care unit, can be
      filled with surgeons capable of converting time saved from parallel processing
      into incremental volume. DESIGN: Statistical and mathematical modeling. SETTING:
      Academic medical center with 52 serial-processing ORs, 1 parallel-processing OR,
      and a congested postanesthesia care unit. PARTICIPANTS: Elective surgical cases
      (N = 58 356) performed by a single surgical service without a preoperative
      intensive care unit bed request from April 1, 2004, through March 31, 2006.
      INTERVENTIONS: Results from our parallel-processing OR (n = 1729) were
      extrapolated to all other cases (n = 56 627) to estimate the duration of key
      process time intervals as if they were performed using parallel processing. Cases
      that could yield incremental throughput using parallel processing were labeled
      "good." Total good case hours per week were then aggregated for each surgeon.
      Main Outcomes Measures Surgeons with 4.5 hours per week or more of good case time
      had a "profile" suitable for a 9-hour block in The Pod every 2 weeks. RESULTS: Of
      the 352 profiled surgeons, 30 had 4.5 hours per week or more of good case time,
      more than filling the 15 blocks per week. CONCLUSIONS: The high-efficiency OR Pod
      can fill each of its 3 ORs with case/surgeon combinations that should yield
      additional throughput. Surgeon profiles based on stringent efficiency targets
      maximize the throughput potential of The Pod's active ORs and more than
      compensate for the OR turned miniature postanesthesia care unit.

PMID- 17438173
TI  - Quality assessment in high-acuity surgery: volume and mortality are not enough.
AB  - HYPOTHESIS: A new quality assessment model for high-acuity surgery links process
      improvements with hospital costs and patient-centered outcomes and accurately
      reflects the clinical and economic impact of variance in patient acuity at the
      level of the practice and health care professional. DESIGN: Retrospective case
      series and cost analysis. SETTING: University tertiary care referral center.
      PATIENTS: A total of 296 patients undergoing elective pancreatic resection in 5
      years. MAIN OUTCOME MEASURES: Expected preoperative morbidity (evaluated using
      POSSUM [Physiologic and Operative Severity Score for the Enumeration of Mortality
      and Morbidity]) was compared with observed morbidity (according to the Clavien
      complication scheme) and was correlated with total hospital costs per patient.
      RESULTS: As volume increased annually, patient acuity (expected morbidity) rose
      and complications declined. Overall, observed and expected morbidity rates were
      equal (54.1% vs 55.1%), for an observed-expected ratio of 0.98. Process
      improvement measures contributed to a steady decrease in the observed-expected
      morbidity ratio from 1.34 to 0.81 during the 5-year period. This decrease was
      strongly associated with significant cost savings as total costs per patient
      declined annually (from $31 541 to $18 829). This performance assessment model
      predicts that a 0.10 decrease in the observed-expected morbidity ratio equates to
      a $2549 cost savings per patient in our practice. CONCLUSIONS: Despite increasing
      patient acuity, better clinical and economic outcomes were achieved across time.
      Approaches that mitigate the impact of preoperative risk can effectively deliver
      quality improvement, as illustrated by a reduced observed-expected morbidity
      ratio. This approach is valuable in analyzing performance and process
      improvements and can be used to assess intrapractice and interpractice variations
      in high-acuity surgery.

PMID- 17438174
TI  - Lifelong surgical education: adapt, change, or wither.

PMID- 17438175
TI  - Image of the month. Kasabach-Merritt syndrome in a giant cavernous liver
      hemangioma.

PMID- 17438176
TI  - Image of the month. Cystic mesothelioma.

PMID- 17438177
TI  - Staged hair transplantation in cicatricial alopecia after carbon dioxide laser
      assisted scar tissue remodeling.

PMID- 17438178
TI  - A randomized, double-blind, placebo-controlled trial of pentoxifylline for the
      treatment of recurrent aphthous stomatitis.
AB  - OBJECTIVE: To evaluate pentoxifylline for the treatment of recurrent aphthous
      stomatitis. DESIGN: A 60-day, randomized, double-blind, placebo-controlled trial
      with a 60-day no treatment follow-up. SETTING: An oral medicine specialist
      referral center in Manchester. PARTICIPANTS: Forty-nine volunteers who passed the
      initial assessment for recurrent aphthous stomatitis entered a pretrial phase in
      which their eligibility for the trial phase of the study was assessed. Sixteen
      subjects were deemed ineligible, and 7 failed to attend or withdrew. The
      remaining 26 subjects were randomized to placebo or treatment. Six subjects
      withdrew because of adverse effects, and 1 was unavailable for follow-up.
      INTERVENTION: Pentoxifylline (also called oxpentifylline), 400 mg 3 times daily,
      or matching placebo. MAIN OUTCOME MEASURE: A reduction in the median pain score,
      ulcer size, number of ulcers, or total number of ulcer episodes. RESULTS:
      Patients taking pentoxifylline had less pain and reported smaller and fewer
      ulcers compared with baseline. Patients taking placebo reported no improvement in
      these variables. Patients taking pentoxifylline also reported more ulcer-free
      days than those taking placebo. However, the differences were small and, with the
      exception of median ulcer size (P = .05), did not reach statistical significance.
      Adverse effects were common with pentoxifylline, but not significantly different
      from those experienced by patients taking placebo. CONCLUSIONS: Although
      pentoxifylline may have some benefit in the treatment of recurrent aphthous
      stomatitis, the benefit is limited. It may have a role in the treatment of
      patients unresponsive to other treatments, but cannot yet be recommended as a
      first-line treatment.

PMID- 17438179
TI  - Treatment of oral erosive lichen planus with 1% pimecrolimus cream: a double
      blind, randomized, prospective trial with measurement of pimecrolimus levels in
      the blood.
AB  - OBJECTIVES: To evaluate the efficacy of 1% pimecrolimus cream in treating oral
      erosive lichen planus and to assess its tolerance. DESIGN: Double-blind
      randomized trial with placebo control. SETTING: Outpatients of the Department of
      Dermatology, University Hospital of Nice, from December 21, 2004, to April 19,
      2005. PATIENTS: Fourteen consecutive patients with oral erosive lichen planus
      confirmed by histological examination and with a clinical score superior to 3. Of
      the 14 patients, 2 did not meet the inclusion criteria and 12 were enrolled in
      the trial. INTERVENTION: The intervention was 1% pimecrolimus cream or its
      vehicle, which was applied on ulcerated lesions twice a day for 4 weeks. MAIN
      OUTCOME MEASURES: The efficacy of the treatment was quantified using a 12-point
      clinical score. The blood level of pimecrolimus was analyzed on days 0
      (baseline), 14, and 28. RESULTS: In the placebo group, the mean score was 4.67 on
      day 0 vs 3.33 on day 28 (P = .22). In the pimecrolimus group, the mean score was
      6.83 on day 0 vs 3.33 on day 28 (P = .04). In the pimecrolimus group, blood
      concentrations of pimecrolimus were always above the threshold (mean value, 2.84
      ng/mL; extreme values, 0-6.19 ng/mL). Pimecrolimus cream was well tolerated, and
      only transient burning sensations were reported by some subjects. Each of the
      patients in the pimecrolimus group whose condition improved subsequently relapsed
      when assessed 1 month after treatment. CONCLUSIONS: The 1% pimecrolimus cream
      seems to be an effective and well-tolerated treatment for oral erosive lichen
      planus. The finding of systemic levels of pimecrolimus after mucosal applications
      necessitates long-term study because it seems that long-term application is
      required to maintain clinical improvement.

PMID- 17438180
TI  - Store-and-forward teledermatology in skin cancer triage: experience and
      evaluation of 2009 teleconsultations.
AB  - OBJECTIVE: To evaluate a store-and-forward teledermatology system aimed at the
      routine triage of patients with skin cancer. DESIGN: A multicenter, longitudinal,
      4-phase, descriptive and evaluation study of a referred sample of patients
      attended through teleconsultation between March 2004 and July 2005 (n = 2009).
      Clinical and dermoscopical examination and histopathological study were
      considered the gold standard. SETTING: A skin cancer unit of a public university
      hospital and 12 primary care centers in southern Spain. PATIENTS: The study
      population comprised patients with circumscribed lesions fulfilling at least 1 of
      the following criteria: changes in ABCD criteria (asymmetry, border irregularity,
      color variegation, and diameter >6 mm), recent history, multiple melanocytic
      lesions, symptoms, and/or patient's application for surgical treatment and
      concern about moles. INTERVENTIONS: Diagnosis, diagnostic category (malignant
      lesions, high-risk lesions, benign lesions, special lesions, and other lesions),
      diagnostic confidence level on a 3-point scale, and management decision (referral
      vs nonreferral) were listed after the evaluation of each teleconsultation. A face
      to-face evaluation and biopsy of selected patients were performed. MAIN OUTCOME
      MEASURES: The filtering percentage, as the percentage of patients not referred to
      the face-to-face clinic, as well as waiting intervals and pick-up or skin cancer
      detection rates were evaluated as effectiveness indicators. Reliability measures
      (kappa agreement), accuracy, and diagnostic performance indicators (validity)
      were also evaluated. RESULTS: The filtering percentage was 51.20% (95% confidence
      interval [CI], 49.00%-53.40%). The waiting interval to attend the clinic was
      12.31 days (95% CI, 8.22-16.40 days) through teledermatology and 88.62 days (95%
      CI, 38.42-138.82 days; P<.001) for the letter referral system. Pick-up rates were
      2.02% (95% CI, 1.10%-2.94%) for malignant melanoma and 27.94% (95% CI, 24.98%
      30.90%) or 1:3.71 for patients with any malignant or premalignant lesion.
      Intraobserver agreement was kappa = 0.91 (95% CI, 0.89-0.93) for the management
      decision and kappa = 0.95 (95% CI, 0.94-0.96) for the diagnosis. Interobserver
      concordance was kappa = 0.83 (95% CI, 0.78-0.88) for the management decision and
      kappa = 0.85 (95% CI, 0.79-0.91) for the diagnosis. Accuracy was kappa = 0.81
      (95% CI, 0.78-0.84). Sensitivity was 0.99 (95% CI, 0.98-1.00); specificity, 0.62
      (95% CI, 0.56-0.69); pretest likelihood, 0.42 (95% CI, 0.37-0.47); positive
      posttest likelihood, 0.65 (95% CI, 0.61-0.69); and negative posttest likelihood,
      0.01 (95% CI, 0.00-0.05). CONCLUSION: Store-and-forward teledermatology has
      demonstrated in this series to be an effective, accurate, reliable, and valid
      approach for the routine management of patient referrals in skin cancer and
      pigmented lesion clinics.

PMID- 17438181
TI  - Melanoma outcomes for Medicare patients: association of stage and survival with
      detection by a dermatologist vs a nondermatologist.
AB  - OBJECTIVE: To determine whether a difference in melanoma outcomes exists in the
      United States between tumors detected by dermatologists vs those detected by
      nondermatologists. DESIGN: Retrospective analysis of linked data from the
      Medicare enrollment and claims files from the Centers for Medicare and Medicaid
      Services and the National Cancer Institute's Surveillance, Epidemiology, and End
      Results program database from 1991 to 1996. The registries are from 12 US sites.
      PATIENTS: A study sample comprised of 2020 subjects. MAIN OUTCOME MEASURES: Tumor
      characteristics (Breslow thickness and histologic ulceration), stage at
      diagnosis, and survival and mortality rates. RESULTS: Tumor detection by a
      dermatologist vs nondermatologist was associated with an earlier stage melanoma
      (stage 0, stage I, and stage II vs stage III and stage IV; chi(2) test, P<.01)
      and a thinner tumor (Breslow thickness, 0.86 mm vs 1.00 mm; P<.05). At all time
      points (6 months, 2 years, and 5 years), patients whose melanoma was detected by
      dermatologists had better survival rates (98%, 87%, and 74%, respectively, for
      those whose melanoma was detected by dermatologists vs 95%, 79%, and 69%,
      respectively, for nondermatologists; P<.05). Non-cancer-related mortality was
      similar for the 2 groups, but the patients whose tumors were detected by
      dermatologists had lower cancer-related mortality (13% vs 21%; P<.01) and overall
      mortality (29% vs 37%; P<.01). Multivariate analysis showed that age, sex, stage
      at diagnosis, and melanoma detection by a dermatologist were all significantly
      predictive of survival. CONCLUSIONS: Earlier stage melanoma and improved survival
      are associated with detection by a dermatologist rather than by a
      nondermatologist. Increasing access to dermatologists, particularly for older
      patients, may represent one approach to improving melanoma-related health
      outcomes.

PMID- 17438182
TI  - Multiple melanomas after treatment for Hodgkin lymphoma in a non-Dutch p16-Leiden
      mutation carrier with 2 MC1R high-risk variants.
AB  - BACKGROUND: A 19-base pair germline deletion in exon 2 of the CDKN2A (cyclin
      dependent kinase inhibitor 2A) gene (Leiden mutation) has been detected in Dutch
      families with familial melanomas. The penetrance of CDKN2A mutations varies
      widely and is influenced by environmental and unrelated genetic factors such as
      variants in the MC1R gene. OBSERVATIONS: We describe a 25-year-old German woman
      who developed 8 invasive melanomas and 6 in situ melanomas after radiation
      therapy and polychemotherapy for Hodgkin lymphoma. Genetic testing revealed a
      constitutional CDKN2A Leiden mutation in the proband and her sister, mother, and
      mother's sister. The proband also carried high-risk MC1R variant alleles R151C
      and R160W, which she had inherited from her father and her mother, respectively.
      The less affected mutation carrier sister did not have high-risk MC1R variant
      alleles. Analysis of DNA from paraffin-embedded tissues showed loss of
      heterozygosity at CDKN2A loci in all 3 melanomas studied but not in Hodgkin
      lymphoma. The pedigree revealed several types of cancers on both sides of the
      family, but no Dutch ancestors were found. No mutations in the CDK4, B-raf, and N
      ras genes were detected either in the germline or in tumors from the patient.
      CONCLUSION: This study shows the variability of the penetrance of the CDKN2A
      Leiden mutation within the same family, which could be due to genetic or
      exogenous factors.

PMID- 17438183
TI  - AKT1 overexpression in endothelial cells leads to the development of cutaneous
      vascular malformations in vivo.
AB  - BACKGROUND: Vascular malformations are clinical disorders in which endothelial
      cells fail to remodel and/or undergo programmed cell death, leading to abnormal
      persistence of blood vessels. The abnormal persistence of vessels makes therapy
      difficult because these lesions are resistant to interventions that are effective
      against hemangiomas. Akt1 is a serine-threonine protein kinase, which is a key
      mediator of resistance to programmed cell death. Our objective was to determine
      whether sustained activation of Akt1 could lead to vascular malformation in mice.
      OBSERVATIONS: We examined the effect of constitutive activation of Akt1 in murine
      endothelial cells (MS1 cells). Overexpression of active AKT1 in MS1 cells led to
      the development of vascular malformations, characterized by wide endothelial
      lumens and minimal investment of smooth muscle surrounding the vessels. The
      histologic features of these vascular malformations is distinct from ras
      transformed MS1 cells (angiosarcoma) and suggest that differing signal
      abnormalities give rise to human vascular malformations vs malignant vascular
      tumors. CONCLUSIONS: Inhibition of Akt signaling may be useful in the treatment
      of vascular malformations. Examination of problematic hemangiomas and vascular
      malformations for the presence of activated Akt or downstream targets of Akt,
      such as mammalian target of rapamycin (mTOR), may predict response to treatment
      with Akt inhibitors or rapamycin. This study provides a potential rationale for
      the systemic and topical use of these inhibitors for vascular malformations and
      hemangiomas.

PMID- 17438184
TI  - Cosmetic permanent fillers for soft tissue augmentation: a new contraindication
      for interferon therapies.
AB  - BACKGROUND: Most of the new fillers used for soft tissue augmentation in
      aesthetic dermatology are considered well tolerated, but very little data are
      available on their long-term tolerability, especially in patients receiving
      immunomodulatory therapy. OBSERVATIONS: A 48-year-old woman presented with
      disfiguring facial edema 10 weeks after she began antiviral therapy with
      peginterferon alfa-2a and ribavirin for chronic hepatitis C infection. The major
      affected sites had been treated 10 years before with Artecoll, a permanent filler
      containing polymethylmethacrylate. A treatment attempt with allopurinol was
      initiated while antiviral therapy was continued and was successfully completed
      after 6 months. Despite significant improvement, extended plastic surgery was
      necessary for facial reconstruction. CONCLUSIONS: The normal host response to a
      cosmetic filler is a weak granulomatous reaction. Interferon and other
      immunostimulatory medications can lead to an exacerbation of this preexisting low
      grade chronic inflammation that is quite similar to interferon-triggered
      sarcoidosis. This potential long-term risk has medicolegal implications for
      informed consent and for the potential use of both permanent fillers and
      interferon.

PMID- 17438185
TI  - Oral lichen planus: a case series with emphasis on therapy.
AB  - BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disorder that can
      cause local irritation and discomfort with attendant poor dentition and
      nutrition. Although a range of therapeutic options is available, data on the long
      term efficacy of treatments for this chronic disease are limited. To identify
      agents that might be effective in OLP treatment over a longer term, and to
      explore their sequential use in treatment-refractory patients, we studied
      patients who received multiple OLP therapies and who were followed up for an
      average of more than 2 years. OBSERVATIONS: We performed a retrospective medical
      record review of 50 patients with histologically confirmed OLP. Patients were
      treated according to a therapeutic ladder of sequential treatments, beginning
      with topical corticosteroids and progressing through topical immunomodulators,
      systemic retinoids, methotrexate, and thalidomide. The best responses were
      observed in previously untreated patients. Most patients eventually achieved a
      substantial response with limited toxic effects. CONCLUSIONS: Our results
      identify low-dose methotrexate as an agent with substantial activity in OLP. We
      also demonstrate that a laddered therapeutic approach to patients with this
      disease can achieve substantial lesion regression even in heavily pretreated and
      treatment-refractory patients.

PMID- 17438186
TI  - New and old therapeutics for oral ulcerations.

PMID- 17438187
TI  - Phenotypic variation in familial melanoma: consequences for predictive DNA
      testing.

PMID- 17438188
TI  - Indoor UV tanning youth access laws: update 2007.

PMID- 17438189
TI  - Papules and plaques on the nose. Nodular localized primary cutaneous amyloidosis.

PMID- 17438190
TI  - Erythema and blistering of the left leg. Fixed drug eruption (FDE).

PMID- 17438191
TI  - Tender erythema of the left lower extremity. Disseminated Aspergillus fumigatus
      infection with concurrent active cytomegalovirus infection (CMV).

PMID- 17438192
TI  - Keratotic papules on the right side of the neck and back. Localized Darier
      disease (DD).

PMID- 17438193
TI  - Melanoma of the foot and ankle: a case series of an underrecognized entity.

PMID- 17438194
TI  - Treatment of hyperhidrosis with oxybutynin.

PMID- 17438195
TI  - Topical calcineurin inhibitors revisited.

PMID- 17438196
TI  - Tuberous necrobiosis lipoidica.

PMID- 17438197
TI  - National Eczema Association and topical calcineurin inhibitor labeling.

PMID- 17438198
TI  - Histopathologic findings of disseminated coccidioidomycosis with hyphae.

PMID- 17438199
TI  - Involution: the natural evolution of pigmented Spitz and Reed nevi?

PMID- 17438200
TI  - Dermoscopic vascular patterns in nodular "pure" amelanotic melanoma.

PMID- 17438201
TI  - Molecular phylogenetic and embryological evidence that feeding larvae have been
      reacquired in a marine gastropod.
AB  - Evolutionary transitions between different modes of development in marine
      invertebrates are thought to be biased toward the loss of feeding larvae. Because
      the morphology of feeding larvae is complex and nonfeeding larvae or encapsulated
      embryos with benthic development often have simplified morphologies, it is
      presumed to be easier to lose a larval stage than to reacquire it. Some authors
      have gone so far as to suggest that feeding larvae, morphologically similar to
      the ancestral feeding larvae, cannot be reacquired. However, the larval
      structures of some groups, most notably gastropods, are often retained in the
      encapsulated embryos of species that hatch as benthic juveniles. Therefore the re
      evolution of feeding larvae using the same structures may be possible in these
      groups. Here we present the first well-substantiated case for the recent re
      evolution of feeding larvae within a clade of direct-developers. DNA sequence
      data show that Crepipatella fecunda, a species of calyptraeid gastropod with
      planktotrophic development, is nested within a clade of species with direct
      development, and that Crepipatella dilatata, a species with direct development,
      appears to be paraphyletic with respect to C. fecunda. Observation of the embryos
      of C. dilatata shows that the features necessary for larval feeding and swimming
      are retained in the encapsulated veligers, suggesting that heterochronic shifts
      in hatching time and changes in nurse-egg allotment could have resulted in the re
      evolution of feeding larvae in this species.

PMID- 17438202
TI  - Time and extent of ciliary response to particles in a non-filtering feeding
      mechanism.
AB  - Mechanisms of suspension feeding are usually described by the physics of
      inanimate filters. High-speed videorecordings in this study demonstrated that sea
      urchin larvae concentrate particles without filtration. They actively captured
      individual particles. At most times and places, the effective strokes of the
      swimming/feeding ciliary band were away from the circumoral field. Cilia of this
      band responded to particles by a reversal of beat that redirected the particle
      toward the circumoral field. A change of beat occurred along approximately 80
      micro m of ciliary band during particle capture. Cilia responded 0.02 to 0.06 s
      after the particle was within reach of effective strokes and reversed beat,
      usually for about 0.1 to 0.2 s. The whole event (disruption of forward beat)
      generally lasted between 0.13 and 0.5 s. These observations imply reversed
      movement of a parcel of water much larger than the included captured particle,
      but particles are nevertheless greatly concentrated because water is directed
      toward the circumoral field only when and where a particle is sensed. Thus most
      of the concentration of particles occurs by a temporarily and locally redirected
      current, without filtration, and size and quality of particles captured depends
      on sensory capabilities, not the mechanics of filtration.

PMID- 17438203
TI  - Biomechanics and energy cost of the amphipod Corophium volutator filter-pump.
AB  - The integrated function of the setal filter-basket and the pleopodal pump in the
      burrowing amphipod Corophium volutator was studied by video-microscopy in order
      to evaluate the energy costs of filter feeding. Video-microscope observations
      indicated that, in general, nine short, water-pumping beat cycles of the pleopods
      are succeeded by one slow cycle that coincides with cleaning of the setal filter
      and transient slowdown of inhalant water velocity. The position of the plumose
      setal filter on the second pair of gnathopods ensures that all water runs through
      the filter-basket. The fine V-shaped bristles on the setae enlarge the total
      filter area so that the velocity of water flowing through the filter is
      relatively slow, about 2.5 mm s(-1), giving rise to a resistance of about 2.9 mm
      H(2)O, which is the most important contribution to the total pressure drop in the
      system. In "standard" individuals of C. volutator with lengths of 3 and 6 mm, the
      normal operating pump pressure and pumping rate were, respectively, 2.6 and 3.1
      mm H(2)O, and 18.3 and 85.5 ml h(-1); the overall pump efficiencies were 5.1% and
      11.6%, respectively. These results show that the Corophium filter-pump is
      comparable to other low-pressure biological pumps in filter-feeding marine
      invertebrates, such as mussels, polychaetes, ascidians, and bryozoans.

PMID- 17438204
TI  - Cost of protein synthesis and energy allocation during development of antarctic
      sea urchin embryos and larvae.
AB  - Cold environments represent a substantial volume of the biosphere. To study
      developmental physiology in subzero seawater temperatures typically found in the
      Southern Ocean, rates and costs of protein synthesis were measured in embryos and
      larvae of Sterechinus neumayeri, the Antarctic sea urchin. Our analysis of the
      "cost of living" in extreme cold for this species shows (1) that cost of protein
      synthesis is strikingly low during development, at 0.41 +/- 0.05 J (mg protein
      synthesized)(-1) (n = 16); (2) that synthesis cost is fixed and independent of
      synthesis rate; and (3) that a low synthesis cost permits high rates of protein
      turnover at -1 degrees C, at rates comparable to those of temperate species of
      sea urchin embryos developing at 15 degrees C. With a low synthesis cost, even at
      the highest synthesis rates measured (gastrulae), the proportion of total
      metabolism accounted for by protein synthesis in the Antarctic sea urchin was 54%
      a value similar to that of temperate sea urchin embryos. In the Antarctic sea
      urchin, up to 87% of metabolic rate can be accounted for by the combined energy
      costs of protein synthesis and the sodium pump. We conclude that, in Antarctic
      sea urchin embryos, high rates of protein synthesis can be supported in extreme
      cold environments while still maintaining low rates of respiration.

PMID- 17438205
TI  - Kinematics of soft-bodied, legged locomotion in Manduca sexta larvae.
AB  - Caterpillar crawling is distinct from that of worms and molluscs; it consists of
      a series of steps in different body segments that can be compared to walking and
      running in animals with stiff skeletons. Using a three-dimensional kinematic
      analysis of horizontal crawling in Manduca sexta, the tobacco hornworm, we found
      that the phase of vertical displacement in the posterior segments substantially
      led changes in horizontal velocity and the segments appeared to pivot around the
      attached claspers. Both of the motions occur during vertebrate walking. In
      contrast, vertical displacement and horizontal velocity in the anterior proleg
      bearing segments were in phase, as expected for running gaits coupled by elastic
      storage. We propose that this kinematic similarity to running results from the
      muscular compression and release of elastic tissues. As evidence in support of
      this proposal, the compression and extension of each segment were similar to
      harmonic oscillations in a spring, although changes in velocity were 70 degrees
      out of phase with displacement, suggesting that the spring was damped.
      Measurements of segment length within, and across, intersegmental boundaries show
      that some of these movements were caused by folding of the body wall between
      segments. These findings demonstrate that caterpillar crawling is not simply the
      forward progression of a peristaltic wave but has kinetic components that vary
      between segments. Although these movements can be compared to legged locomotion
      in animals with stiff skeletons, the underlying mechanisms of caterpillar
      propulsion, and in particular the contribution of elastic tissues, remain to be
      discovered.

PMID- 17438206
TI  - How does metabolic rate scale with egg size? An experimental test with sea urchin
      embryos.
AB  - The consequences of changes in egg size for the development of marine
      invertebrates have been the subject of much theoretical and experimental work.
      Models that explore larval developmental modes in the context of maternal
      investment per offspring are often couched in an energetic framework, but the
      relationships between egg size and the energetics of larval development are
      poorly understood. We used blastomere separations to examine how experimental
      reductions in egg size affected (1) larval metabolic rate and (2) larval
      resistance to starvation. We found that separating blastomeres at the 2- and 4
      cell stage resulted in average reductions of 50% and 75%, respectively, in larval
      metabolic rate. This suggests that, in an experimental context, mass-specific
      metabolic rate does not change with egg size. We also found that a 50% reduction
      in egg volume did not reduce the resistance of larvae to starvation when
      particulate food was withheld. This suggests that the material supplied to larvae
      in the egg is used primarily for construction of the larval body, rather than as
      a buffer against starvation or as a means of reducing reliance on exogenous fuel
      to sustain maintenance metabolism.

PMID- 17438207
TI  - Effects of salinity on spawning and early development of the tube-building
      polychaete Hydroides elegans in Hong Kong: not just the sperm's fault?
AB  - Ambient salinities drop dramatically during monsoon season in Hong Kong coastal
      waters, posing a number of problems for externally fertilizing species like the
      polychaete Hydroides elegans. In this study, we investigated (1) whether adults
      would retain their gametes when external salinity dropped to levels too low to
      support fertilization and development, and (2) whether failure of development at
      low salinity reflects a failure of fertilization or a failure of fertilized eggs
      to cleave. Adults released eggs and sperm in the laboratory even at the lowest
      salinity tested, a practical salinity (S) of 5, and yet very few eggs cleaved at
      salinities below about 22. By mixing gametes at high salinity and then
      transferring the fertilized eggs to low-salinity seawater, we found that
      salinities below about 22 reduced the percentage of fertilized eggs that cleaved.
      Similarly, mixing gametes at salinities as low as 15 and then transferring the
      eggs to full-strength seawater (S = 30) rescued a substantial number of eggs,
      many more of which cleaved after their transfer to the higher salinity. The
      results suggest that failure of early development at low salinity in this species
      in large part reflects an inability of newly fertilized eggs to complete meiosis
      and cleave, rather than simply a failure of fertilization.

PMID- 17438208
TI  - Analysis of calcium concentration fluctuations in hepatopancreatic R cells of
      Marsupenaeus japonicus during the molting cycle.
AB  - In this study we examined the fluctuations of the intracellular calcium
      concentration in isolated hepatopancreatic R cells during the four molting stages
      of the prawn Marsupenaeus japonicus. In addition, we used the Fura-2-AM
      fluorescence technique to investigate the release of calcium from mitochondria
      and ATP-sensitive calcium stores (endoplasmic reticulum (ER), Golgi, and nucleus)
      into cytoplasm during the molting cycle. Results demonstrate that both the
      cytosolic free calcium concentration and the total cell calcium (free, bound to
      calcium-binding proteins, and stored in amorphous form) in the R cells strictly
      depend upon the molting cycle. Interestingly, the total cell calcium was higher
      (approximately 10 mmol l(-1)) in postmolt than in premolt (approximately 1 mmol
      l(-1)) and intermolt (approximately 0.3 mmol l(-1)). The calcium released from
      mitochondria was higher during premolt than during postmolt and intermolt, but
      the amount of calcium released from ATP-sensitive calcium stores was similar
      during all four stages. All together, our results suggest that the mitochondria
      ATP-sensitive calcium stores system does not play a key role in calcium storage
      during the molting cycle but that it is involved in transcellular calcium flux.
      We hypothesize that lysosome or membrane-clad concretion vacuoles could represent
      the main site of calcium storage in hepatopancreatic R cells.

PMID- 17438209
TI  - Mitochondrial delivery is essential for synaptic potentiation.
AB  - Mitochondria, as portable generators that power synaptic function, regulate the
      ATP supply and calcium homeostasis in the neuron. As molecular interactions
      within the synapses before and after the potentiation are beginning to be
      elucidated, the deciding moment during the tetanic stimulation that gives rise to
      the strengthening of the synapse remains a mystery. Here, I recorded electrically
      from an intact Drosophila nervous system, while simultaneously using time-lapse
      confocal microscopy to visualize mitochondria labeled with green fluorescent
      protein. I show that tetanic stimulation triggers a fast delivery of mitochondria
      to the synapse, which facilitates synaptic potentiation. Rotenone, an inhibitor
      of mitochondrial electron transport chain complex I, suppresses mitochondrial
      transport and abolishes the potentiation of the synapse. Expression of
      neurofibromin, which improves mitochondrial ATP synthesis in the neuron, enhances
      the movements of mitochondria to the synapse and promotes post-tetanic
      potentiation. These findings provide unprecedented evidence that the
      mitochondrial delivery to the synapse is critical for cellular learning.

PMID- 17438210
TI  - Transient bilateral finger tremor after brain death.

PMID- 17438211
TI  - What's the problem with generic antiepileptic drugs?: a call to action.

PMID- 17438212
TI  - Chili peppers, nerve regeneration, and clinical trial design.

PMID- 17438213
TI  - Position statement on the coverage of anticonvulsant drugs for the treatment of
      epilepsy.

PMID- 17438214
TI  - Impaired reinnervation in HIV infection following experimental denervation.
AB  - OBJECTIVE: To determine whether abnormalities in peripheral nerve regeneration
      are present in HIV-infected individuals. DESIGN: We studied human epidermal nerve
      fiber reinnervation by collateral and regenerative sprouting using validated
      cutaneous nerve injury models in healthy control subjects and those infected with
      HIV. Characteristics associated with the degree of reinnervation were identified.
      METHODS: Seventy-one healthy volunteers and 22 HIV+ individuals underwent topical
      capsaicin treatment at the distal lateral thigh resulting in complete epidermal
      denervation. Regenerative sprouting was quantified in skin biopsies at intervals
      up to 100 days. Five healthy subjects and 5 HIV+ individuals underwent a 3-mm
      distal thigh punch skin biopsy to create an intracutaneous axotomy, followed 2
      months later by a 4-mm overlapping biopsy. The collateral sprouting distance was
      measured. RESULTS: The mean rate of regenerative sprouting was highest for
      healthy control subjects (0.17 +/- 0.073 fibers/mm/day), followed by HIV+
      subjects without neuropathy (0.13 +/- 0.06) and then HIV+ subjects with
      neuropathy (0.097 +/- 0.07) (p = 0.002). Regenerative sprouting was significantly
      associated with the baseline intraepidermal nerve fiber density (p < 0.001) but
      not with HIV viral load, HIV duration, CD4 cell count, or ApoE epsilon4 status.
      HIV+ individuals were also found to have a reduced collateral sprouting rate
      compared to controls (5.31 mum +/- 0.73 vs 9.78 mum +/- 1.5/day, p = 0.03).
      CONCLUSIONS: Abnormalities in both regenerative and collateral sprouting are
      present in people infected with HIV, and are detectable in subjects with and
      without evidence of peripheral nerve dysfunction. Our results indicate that
      abnormalities in nerve regeneration occur early in HIV infection and provide a
      rationale to include neuropathy-free HIV subjects in regenerative peripheral
      nerve trials.

PMID- 17438215
TI  - Mechanisms of ischemic stroke in HIV-infected patients.
AB  - OBJECTIVE: To evaluate the types and mechanisms of stroke in a large population
      of HIV-infected patients. METHODS: We reviewed records of consecutive HIV
      infected patients with acute stroke admitted to a large metropolitan hospital
      between 1996 and 2004. Stroke mechanism was defined by consensus between two
      cerebrovascular neurologists using TOAST classification. RESULTS: A total of 82
      patients were included, 77 with ischemic stroke and 5 with intracerebral
      hemorrhage. Mean age was 42 years and 89% were African American. Previous
      diagnosis of HIV infection was documented in 91% and AIDS diagnosis in 80%. Mean
      CD4 count was 113 cells/mm(3) and 85% had CD4 count <200 cells/mm(3). A total of
      61% of patients had received combination antiretroviral treatment (CART). The
      mechanism of ischemic stroke was large artery atherosclerosis in 12%, cardiac
      embolism in 18%, small vessel occlusion in 18%, other determined etiology in 23%,
      and undetermined in 29% (including 19% with incomplete evaluation). Vasculitis
      was deemed responsible for the stroke in 10 patients (13%) and hypercoagulability
      in 7 (9%). Protein S deficiency was noted in 10/22 (45%) and anticardiolipin
      antibodies in 9/31 (29%) tested patients. When comparing patients with large or
      small vessel disease (atherothrombotic strokes) vs the rest of the population,
      there were no differences in exposure to CART or CD4 count, but patients with non
      atherothrombotic strokes were younger (p = 0.04). Recent cocaine exposure was
      less common among patients with atherothrombotic strokes (p = 0.02). Strokes were
      fatal or severely disabling in 35% of cases. CONCLUSIONS: Stroke mechanisms are
      variable in HIV-infected patients, with a relatively high incidence of vasculitis
      and hypercoagulability. In our population of severely immunodepressed patients,
      exposure to combination antiretroviral treatment did not significantly influence
      the mechanism of stroke.

PMID- 17438216
TI  - Advanced Parkinson disease treated with rotigotine transdermal system: PREFER
      Study.
AB  - BACKGROUND: In patients experiencing motor fluctuations, a major treatment
      challenge is the reduction of "off" time, particularly upon awakening. Rotigotine
      (Neupro) is a novel dopaminergic agonist with 24-hour transdermal delivery.
      METHODS: A randomized, double-blind, placebo-controlled trial (PREFER Study) was
      performed to assess efficacy and safety with two targeted transdermal doses of
      rotigotine in subjects with advanced Parkinson disease with > or =2.5 hours of
      daily "off" time. Subjects were randomized to receive placebo patches (n = 120)
      or rotigotine up to either 8 mg/24 hours (n = 120) or 12 mg/24 hours (n = 111).
      The primary efficacy measures compared changes from baseline to the end of week
      24 in the number of daily hours "off" and responder rates for subjects achieving
      > or =30% reduction in "off" time. RESULTS: Compared to placebo, there were
      significant decreases in mean "off" time of 1.8 hours/day for the rotigotine 8
      mg/24 hours group and 1.2 hours/day for the 12 mg/24 hours group. For rotigotine
      8 and 12 mg/24 hours groups, > or =30% responder rates were 56.6% and 55.1%
      compared to the 34.5% placebo response. "On" time without dyskinesia after
      awakening was more than doubled in both rotigotine treatment groups vs placebo.
      Drug-related adverse effects included typical dopaminergic side effects, which
      were generally mild/moderate in intensity. Patch application site reactions
      including erythema and pruritus were mild to moderate and transient in the
      majority of instances. CONCLUSIONS: Transdermal rotigotine significantly improved
      "off" time in subjects with Parkinson disease not optimally controlled with
      levodopa and was safe and well tolerated, with typical dopaminergic side effects
      and occasional application site reactions.

PMID- 17438217
TI  - Brain structural alterations before mild cognitive impairment.
AB  - OBJECTIVE: To determine whether alterations of brain structure in normal aged
      individuals precede the development of mild cognitive impairment (MCI) or
      Alzheimer disease (AD). BACKGROUND: Persons with MCI and AD demonstrate cortical
      volume losses vs asymptomatic aged individuals, particularly in the hippocampus,
      amygdala, and entorhinal cortex. It is unknown whether these losses or other
      volumetric changes are present, and to what degree, in cognitively normal
      individuals before the clinical diagnosis of MCI. METHODS: Structural MRI was
      performed on a cross-section of 136 longitudinally examined normal aged subjects.
      All subjects were cognitively normal at the time of their scan, but 23 later
      developed MCI, and 9 of these 23 went on to an AD diagnosis. Extracted volumes
      from voxel-based morphometric analysis were combined with clinical data to
      compare the 23 subjects who eventually developed MCI to 113 subjects who remained
      cognitively normal over an average follow-up of 5.4 years. RESULTS: Initially
      normal subjects who eventually developed MCI demonstrated decreased gray matter
      volumes in the anteromedial temporal lobes bilaterally and left angular gyrus
      while still cognitively normal. CONCLUSION: Structural brain changes in anatomic
      areas involved in higher cognitive processes precede clinical signs and symptoms
      in longitudinally followed normal subjects destined to develop mild cognitive
      impairment.

PMID- 17438218
TI  - Cognitive and motor assessment in autopsy-proven corticobasal degeneration.
AB  - OBJECTIVE: To investigate the clinical features of autopsy-proven corticobasal
      degeneration (CBD). METHODS: We evaluated symptoms, signs, and neuropsychological
      deficits longitudinally in 15 patients with autopsy-proven CBD and related these
      observations directly to the neuroanatomic distribution of disease. RESULTS: At
      presentation, a specific pattern of cognitive impairment was evident, whereas an
      extrapyramidal motor abnormality was present in less than half of the patients.
      Follow-up examination revealed persistent impairment of apraxia and executive
      functioning, worsening language performance, and preserved memory. The motor
      disorder emerged and worsened as the condition progressed. Statistical analysis
      associated cognitive deficits with tau-immunoreactive pathology that is
      significantly more prominent in frontal and parietal cortices and the basal
      ganglia than temporal neocortex and the hippocampus. CONCLUSION: The clinical
      diagnosis of corticobasal degeneration should depend on a specific pattern of
      impaired cognition as well as an extrapyramidal motor disorder, reflecting the
      neuroanatomic distribution of disease in frontal and parietal cortices and the
      basal ganglia.

PMID- 17438219
TI  - Health care costs decline after successful epilepsy surgery.
AB  - BACKGROUND: Surgery is an effective, high-cost procedure used increasingly to
      treat refractory epilepsy. For surgery to be cost-effective, long-term cost
      savings from reduced health care use should provide some offset to the initial
      costs of evaluation and surgery. There is little information about how health
      care costs are affected by evaluation and surgery. OBJECTIVE: To determine
      whether health care costs change when seizures become controlled after surgery.
      METHODS: Health care costs for the 2 years prior to surgical evaluation and for 2
      years afterward were calculated from medical records of 68 subjects with temporal
      lobe epilepsy (TLE) participating in a multicenter observational study. Costs
      were compared among patients who did not have surgery, patients who had
      persisting seizures after surgery, and patients who were seizure free after
      surgery. RESULTS: Antiepileptic drugs (AEDs) accounted for more than half of the
      costs of care in the pre-evaluation period. Total costs for seizure-free patients
      had declined 32% by 2 years following surgery due to less use of AEDs and
      inpatient care. Costs did not change in patients with persisting seizures,
      whether they had surgery or not. In the 18 to 24 months following evaluation,
      epilepsy-related costs were $2,068 to $2,094 in patients with persisting seizures
      vs $582 in seizure-free patients. CONCLUSIONS: Costs remain stable over 2 years
      post-evaluation in patients with temporal lobe epilepsy whose seizures persist,
      but patients who become seizure free after surgery use substantially less health
      care than before surgery. Further cost reductions in seizure-free patients can be
      expected as antiepileptic drugs are successfully eliminated.

PMID- 17438220
TI  - Natalizumab reduces visual loss in patients with relapsing multiple sclerosis.
AB  - OBJECTIVE: To examine the effects of natalizumab on low-contrast letter acuity as
      a prespecified tertiary endpoint in two randomized clinical trials and to
      evaluate the usefulness of low-contrast letter acuity testing as a candidate test
      of visual function in multiple sclerosis (MS). METHODS: AFFIRM and SENTINEL were
      randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical
      trials of natalizumab in relapsing MS. Natalizumab was evaluated as monotherapy
      in AFFIRM and as add-on to interferon beta-1a in SENTINEL. Vision testing was
      performed at 100% contrast (visual acuity) and low-contrast (2.5% and 1.25%).
      RESULTS: The risk of clinically significant visual loss (predefined as a two-line
      worsening of acuity sustained over 12 weeks) at the lowest contrast level (1.25%)
      was reduced in the natalizumab treatment arms by 35% in AFFIRM (hazard ratio =
      0.65; 95% CI: 0.47 to 0.90; p = 0.008) and by 28% in SENTINEL (hazard ratio =
      0.72; 95% CI: 0.54 to 0.98; p = 0.038, Cox proportional hazards models). Mean
      changes in vision scores from baseline were also significantly different,
      reflecting worsening in non-natalizumab groups. CONCLUSIONS: Natalizumab reduces
      visual loss in patients with relapsing multiple sclerosis. Low-contrast acuity
      testing has the capacity to demonstrate treatment effects and is a strong
      candidate for assessment of visual outcomes in future multiple sclerosis trials.

PMID- 17438221
TI  - Steroid-responsive neurologic relapses in a child with a proteolipid protein-1
      mutation.
AB  - A 10-year-old boy developed corticosteroid-responsive relapsing neurologic signs,
      including nystagmus and ataxia. MRI revealed multifocal T2 white matter
      hyperintensities; several were gadolinium-enhancing. CSF contained oligoclonal
      bands. Although the patient met criteria for multiple sclerosis (MS), the
      proteolipid protein-1 gene (PLP1) contained a mutation in exon 3B (c.409C>T),
      predicting a tryptophan-for-arginine substitution. This case raises questions
      about the role of inflammation in PLP1-related disorders and, conversely, PLP1
      mutations in MS.

PMID- 17438222
TI  - Parry Romberg syndrome and linear scleroderma in coup de sabre mimicking
      Rasmussen encephalitis.
AB  - We present one patient with Parry Romberg syndrome and another with linear
      scleroderma in coup de sabre, with focal neurologic deficits and intractable
      seizures arising from the hemisphere ipsilateral to the cutaneous lesion. Brain
      MRI showed progressive hemispheric atrophy. Pathology after functional
      hemispherectomy showed chronic inflammatory features suggestive of Rasmussen
      encephalitis.

PMID- 17438223
TI  - How accurate are bedside hearing tests?
AB  - The accuracy of five bedside hearing tests was evaluated in 107 consecutive
      adults, using pure-tone audiometry as the standard reference. Bedside tests had
      poor sensitivity (< or =0.60), relatively good specificity (> or =0.74), and
      variable positive predictive value (0.24 to 1.0) for detecting hearing loss.
      Sensitivity improved when bedside tests were combined with case history. The
      diagnostic utility of bedside tests routinely administered by neurologists to
      detect hearing loss in adults requires further study.

PMID- 17438224
TI  - Rho GTPases: role in dendrite and axonal growth, mental retardation, and axonal
      regeneration.

PMID- 17438225
TI  - Bilateral medial temporal lesions in Japanese encephalitis.

PMID- 17438226
TI  - Vigabatrin improves paroxysmal dystonia in succinic semialdehyde dehydrogenase
      deficiency.

PMID- 17438227
TI  - Palinacousis in temporal lobe intracerebral hemorrhage.

PMID- 17438228
TI  - Alexander disease with hypothermia, microcoria, and psychiatric and endocrine
      disturbances.

PMID- 17438229
TI  - Subarachnoid hemorrhage is followed by temporomesial volume loss: MRI volumetric
      study.

PMID- 17438230
TI  - Survey of training programs' means for promoting neurology and attracting
      trainees.

PMID- 17438231
TI  - Atypical antipsychotics in the elderly with Parkinson disease and the "black box"
      warning.

PMID- 17438232
TI  - Speech and language delay are early manifestations of juvenile-onset Huntington
      disease.

PMID- 17438233
TI  - Occurrence of CNS demyelinating disease in patients with myasthenia gravis.

PMID- 17438234
TI  - Differential diagnosis and evaluation in pediatric multiple sclerosis.
AB  - The differential diagnosis for multiple sclerosis (MS) in childhood and
      adolescence includes infectious, inflammatory, and neoplastic disorders as well
      as metabolic neurogenetic leukodystrophies, toxic leukodystrophies, and vascular
      conditions. The evaluation is determined by the clinical and neuroradiologic
      presentation. A minimal diagnostic battery is proposed. More expanded evaluations
      are indicated for specific or atypical clinical presentations.

PMID- 17438235
TI  - Acute disseminated encephalomyelitis.
AB  - Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory
      disorder of the CNS characterized by a widespread demyelination that
      predominantly involves the white matter of the brain and spinal cord. The
      condition is usually precipitated by a viral infection or vaccination. The
      presenting features include an acute encephalopathy with multifocal neurologic
      signs and deficits. Children are preferentially affected. In the absence of
      specific biologic markers, the diagnosis of ADEM is still based on the clinical
      and radiologic features. Although ADEM usually has a monophasic course, recurrent
      or multiphasic forms have been reported, raising diagnostic difficulties in
      distinguishing these cases from multiple sclerosis (MS). The International
      Pediatric MS Study Group proposes uniform definitions for ADEM and its variants.
      We discuss some of the difficulties in the interpretation of available literature
      due to the different terms and definitions used. In addition, this review
      summarizes current knowledge of the main aspects of ADEM, including its clinical
      and radiologic diagnostic features, epidemiology, pathogenesis, and outcome. An
      overview of ADEM treatment in children is provided. Finally, the controversies
      surrounding pediatric MS and ADEM are addressed.

PMID- 17438236
TI  - Pediatric multiple sclerosis: a short history of a long story.
AB  - Shortly after multiple sclerosis (MS) was described by Charcot in 1872-1873,
      symptoms of MS were noted in children. At the time of these observations (late
      19th century), the many inherited demyelinating diseases that manifest during
      childhood had not yet been recognized. Once the inherited demyelinating disorders
      became known, MS as a childhood disease was dismissed as a possible diagnosis.
      Only a half century later, with increased understanding of both inherited
      leukodystrophies as well as MS, was it acknowledged that children can develop MS.
      Our present challenges in the differential diagnoses of demyelinating disorders
      presenting in childhood are reflected in the history of pediatric MS.

PMID- 17438237
TI  - Clinical features of children and adolescents with multiple sclerosis.
AB  - There is increasing appreciation that multiple sclerosis (MS) can begin in
      childhood or adolescence, but pediatric MS continues to be a rare entity, with an
      estimated 2 to 5% of patients with MS experiencing their first clinical symptoms
      before age 16. A prompt diagnosis of pediatric MS is important to optimize
      overall management of both the physical and social impact of the disease. The
      widespread use of disease-modifying therapies (DMT) for MS in adults, as early as
      following an initial isolated episode, has led to the use of DMT in children and
      adolescents with MS. However, it is imperative to distinguish pediatric MS from
      other childhood CNS inflammatory demyelinating disorders such as acute
      disseminated encephalomyelitis. Although increasing evidence suggests a slower
      disease course in children with MS compared to adults, significant disability can
      still accumulate by early adulthood. Furthermore, associated neurocognitive
      deficits can impair both academic and psychosocial function at a critical
      juncture in a young person's life. This article reviews the clinical
      characteristics, neuroimaging, paraclinical findings, disease course,
      epidemiology, genetics, and pathophysiology of pediatric MS vis-a-vis adult MS.
      Further research of pediatric MS may advance our understanding of MS
      pathophysiology in general, as well as improve the long-term health care outcomes
      of children and adolescents diagnosed with MS.

PMID- 17438238
TI  - MRI features of pediatric multiple sclerosis.
AB  - BACKGROUND: MRI has revolutionized the diagnostic accuracy of multiple sclerosis
      (MS) in adults, and is now used extensively to evaluate efficacy of
      immunomodulatory therapies. Although MRI has also been used to aid in the
      diagnosis and care of children with MS, the MRI features of MS in children are
      less well understood. METHODS: The present review summarizes the available
      literature on MRI in pediatric MS, outlines the specific features of other
      disorders affecting the CNS white matter in children, compares the MRI appearance
      of MS in children to seminal neuroimaging studies in adult-onset MS, and
      discusses the potential role of advanced MRI technologies in delineating the
      underlying pathobiology of acquired demyelinating disease in children. RESULTS:
      Although the MRI features of MS in children have similarity to adult-onset MS,
      children tend to have fewer lesions and a lower propensity for lesions to enhance
      with gadolinium. The MRI findings in children presenting with a clinical
      phenotype of acute disseminated encephalomyelitis may be indistinguishable from
      the first attack of MS. CONCLUSIONS: MRI criteria specific for pediatric-onset
      multiple sclerosis (MS) and criteria predictive of MS outcome in children
      experiencing a first demyelinating event will be challenged by the overlap in MRI
      features between acute monophasic demyelinating syndromes and MS, particularly in
      younger children. Emergence of new clinically silent lesions on MRI scans
      separated by at least 3 months is characteristic of MS. Newer MRI techniques
      evaluating white matter biochemistry and integrity in the youngest MS patients
      may provide new insights into the relative contributions of inflammation and
      neurodegeneration in MS.

PMID- 17438239
TI  - Treatment of pediatric multiple sclerosis and variants.
AB  - Studies in adult patients with multiple sclerosis (MS) suggest significant
      benefit of early treatment initiation. However, there are no approved therapies
      for children and adolescents with MS. For adult MS, tolerability and efficacy of
      several immunomodulatory and immunosuppressive drugs have been demonstrated.
      Guidelines for the use of these MS therapies in children do not exist. Several
      small cohort studies of the safety and tolerability of disease-modifying
      therapies (DMT) in children and adolescents with MS have been recently reported.
      The side effects of interferon beta (IFNB) and glatiramer acetate (GA) appear to
      be similar to those reported by adults. The long-term tolerability and safety
      have yet to be established and efficacy data have yet to be studied. In view of
      the potential for significant long-term physical and cognitive disability in
      children with MS, and recent evidence that initiation of immunomodulatory therapy
      early in the course of MS improves long-term prognosis, an increasing number of
      children and adolescents with MS are being offered the DMT approved for adults.
      This review summarizes current knowledge of DMT in pediatric MS and experience in
      several centers treating pediatric MS and MS variants such as neuromyelitis
      optica or Devic disease, Balo concentric sclerosis, Marburg acute MS, and
      Schilder disease (myelinoclastic diffuse sclerosis). Finally, an overview of
      symptomatic MS therapies and experiences with these treatments in pediatric
      patients is provided.

PMID- 17438240
TI  - The psychosocial consequences of pediatric multiple sclerosis.
AB  - Although psychological distress and cognitive dysfunction are well documented in
      adults with multiple sclerosis (MS), they are poorly understood in children with
      the disease. Psychosocial difficulty experienced by children and adolescents with
      MS involves factors common to all chronic illnesses in children, as well as MS
      specific factors. The psychosocial manifestations of the disease may affect the
      patient's self-image, role functioning, mood, and cognition to adversely affect
      schooling, interpersonal relationships, and treatment compliance. Furthermore,
      the impact of having a family member with MS may affect overall family
      functioning. Assessment and interventions for psychosocial and cognitive problems
      in pediatric MS should be multidisciplinary in nature and address the child's
      functioning at home, school, and among peers, as well as the effect on the
      family.

PMID- 17438241
TI  - Consensus definitions proposed for pediatric multiple sclerosis and related
      disorders.
AB  - BACKGROUND: The CNS inflammatory demyelinating disorders of childhood include
      both self-limited and lifelong conditions, which can be indistinguishable at the
      time of initial presentation. Clinical, biologic, and radiographic delineation of
      the various monophasic and chronic childhood demyelinating disorders requires an
      operational classification system to facilitate prospective research studies.
      METHODS: The National Multiple Sclerosis Society (NMSS) organized an
      International Pediatric MS Study Group (Study Group) composed of adult and
      pediatric neurologists and experts in genetics, epidemiology, neuropsychology,
      nursing, and immunology. The group met several times to develop consensus
      definitions regarding the major CNS inflammatory demyelinating disorders of
      children and adolescents. RESULTS: Clinical definitions are proposed for
      pediatric multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM),
      recurrent ADEM, multiphasic ADEM, neuromyelitis optica, and clinically isolated
      syndrome. These definitions are considered operational and need to be tested in
      future research and modified accordingly. CONCLUSION: CNS inflammatory
      demyelinating disorders presenting in children and adolescents can be defined and
      distinguished. However, prospective research is necessary to determine the
      validity and utility of the proposed diagnostic categories.

PMID- 17438242
TI  - Challenges in the classification of pediatric multiple sclerosis and future
      directions.
AB  - To improve care for children with multiple sclerosis (MS) and to advance
      understanding of the underlying biologic mechanisms through collaborative
      research studies, criteria for case definitions of pediatric MS and related CNS
      demyelinating disorders were proposed by the International Pediatric MS Study
      Group. Issues raised during development of these definitions and rationale behind
      criteria proposed are summarized in this article, as are potential international
      multicenter research studies that would be facilitated by the application of a
      uniform set of definitions.

PMID- 17438243
TI  - Maintenance of Certification for American Board of Otolaryngology-certified
      otolaryngologists-head and neck surgeons.

PMID- 17438245
TI  - Slide tracheoplasty applied to acquired subglottic and upper tracheal stenosis:
      an experimental study in a canine model.
AB  - OBJECTIVE: To assess the applicability and complications of slide tracheoplasty
      in the management of subglottic and upper tracheal stenosis in experimental
      animals. DESIGN: Subglottic stenosis was induced in 10 dogs by cauterizing the
      subglottic area and the upper 3 to 4 cm of the trachea. After 21 days, the
      severity of stenosis ranged from 30% to 60%. The subglottic area was
      reconstruction with slide tracheoplasty, and the results were evaluated at 4, 12,
      and 24 weeks postoperatively. SUBJECTS: Ten mongrel dogs (Canis familiaris) were
      included in the study, each weighing between 12 and 17 kg. INTERVENTION: Slide
      tracheoplasty. MAIN OUTCOME MEASURE: Patency of the reconstructed segment.
      RESULTS: Follow-up examination revealed no airway obstruction in any animal.
      Examination of the reconstructed segment revealed good healing without
      granulation tissue and a patent endotracheal lumen in all cases.
      Histopathological examination of sections taken at the suture line confirmed
      complete healing without granulation tissue. CONCLUSIONS: Slide tracheoplasty can
      be applied successfully to the subglottic area. It offers many advantages in
      tracheal reconstruction and can be used for the management of acquired subglottic
      stenosis. The vascularized tracheal cartilage heals without granulation tissue
      often seen after cartilage interposition grafts. Furthermore, this technique
      reduces the need for tracheal and laryngeal mobilization for the treatment of
      longer areas of stenosis.

PMID- 17438244
TI  - Multimodal intensification regimens for advanced, resectable, previously
      untreated squamous cell cancer of the oral cavity, oropharynx, or hypopharynx: a
      12-year experience.
AB  - OBJECTIVE: To determine the feasibility of, compliance with, and long-term
      survival with intensification treatment regimens for patients with advanced,
      resectable, previously untreated head and neck squamous cell carcinoma. DESIGN:
      Prospective phase 2 clinical trial (3 similar, consecutively evolved trials).
      SETTING: Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard
      J. Solove Research Institute, The Ohio State University. PATIENTS: One hundred
      twenty-three patients (median age, 60 years; range, 30-78 years) with previously
      untreated, resectable, advanced squamous cell carcinomas of the oral cavity,
      oropharynx, or hypopharynx. INTERVENTIONS: Perioperative cisplatin
      chemoradiotherapy, surgical resection with intraoperative radiotherapy, and
      postoperative paclitaxel and cisplatin chemoradiotherapy. MAIN OUTCOME MEASURES:
      The feasibility, compliance, and long-term survival associated with the 3
      intensification regimens. RESULTS: Compliance with all 3 intensification regimens
      averaged 61% (75/123). Patient-directed noncompliance occurred in 16 patients
      (13%). The average locoregional (112/123, 91%) and systemic (106/123, 86%)
      disease control rates were excellent. Overall long-term disease-specific survival
      was 73%. Median time at risk was 62.5 months (range, 1 day to 100.4 months).
      CONCLUSIONS: The intensification regimens result in excellent disease control
      rates and long-term survival in this particular patient population. Future
      evolution of these regimens will include some modifications to further decrease
      toxic effects followed by phase 2 multi-institutional trials to determine whether
      the single-institutional experience can be duplicated. The results of these
      studies will determine whether phase 3 trials can be proposed.

PMID- 17438246
TI  - A new clinical olfactory function test: cross-cultural influence.
AB  - OBJECTIVE: To investigate whether a new clinical olfactory test, the Odor Stick
      Identification Test for Japanese (OSIT-J), can be used to assess olfactory
      function cross-culturally in a US patient population. DESIGN: Cross-sectional
      prospective study. SETTING: A university medical center otolaryngology clinic.
      PATIENTS: Fifty US patients presenting with complaints of olfactory dysfunction
      from December 2004 to January 2006. INTERVENTIONS: Olfactory testing and patient
      interview. MAIN OUTCOME MEASURES: Comparison of test results obtained with the
      OSIT-J, the Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory
      function test, and patients' self-reported level of olfactory function. Patients'
      opinions regarding the 2 test methods were also recorded. RESULTS: The mean +/-
      SD time required to administer the OSIT-J (8 +/- 1 minutes) was shorter than that
      required for the standard CCCRC test (21 +/- 6 minutes). Significant Spearman
      rank correlations were found between the OSIT-J and CCCRC test scores (r(s) =
      0.80, P<.001, n = 50), and patients' self-reported level of olfactory function
      (r(s) = 0.73, P<.001, n = 50). Although 3 of the 13 odors used in the OSIT-J were
      not familiar to US subjects, patients reported that the OSIT-J was easier, more
      interesting, and the odors used more pleasant than the CCCRC test. CONCLUSIONS:
      Olfactory function tests developed in different countries should be evaluated to
      determine if a cross-cultural bias exists among test odorants. Although a
      cultural bias was detected for a few odorants, this study demonstrates that a
      modified version of the OSIT-J can be used to assess olfactory function in US
      patients.

PMID- 17438247
TI  - Use of laser for dacrocystorhinostomy.
AB  - OBJECTIVE: To compare outcomes between conventional external dacrocystorhinostomy
      (ext DCR) and endonasal laser-assisted DCR (ELADCR). DESIGN: Prospective
      randomized trial. PATIENTS: The study included 210 consecutive patients (244
      eyes) referred to hospital eye and ear, nose, and throat clinics. MAIN OUTCOME
      MEASURES: Success rates and complications of ext DCR and ELADCR were compared
      after lacrimal ducts requiring DCR were randomly chosen and divided into 2 groups
      (ext DCR and ELADCR). RESULTS: The success rate was statistically equal in both
      groups (92.4% for ext DCR and 94.2% for ELADCR); however, morbidity (eg,
      intraoperative hemorrhage and wound scar) and operation time were less in the
      ELADCR group. CONCLUSION: Preoperative patient consultation for selection of the
      surgical modality may help select the procedure of choice for each patient with
      regard to aesthetics, anesthesia, operation time, and costs.

PMID- 17438248
TI  - Comparison of optical rhinometry and active anterior rhinomanometry using nasal
      provocation testing.
AB  - OBJECTIVE: To investigate whether there is a correlation between active anterior
      rhinomanometry (RMM) and optical rhinometry (ORM) data in the detection of
      changes in nasal congestion. DESIGN: In 70 subjects both ORM and RMM were
      performed. Changes in nasal congestion were induced by nasal provocation with
      histamine, allergens, solvent, and xylometazoline hydrochloride, 0.1%. Using
      visual analog scales, subjects rated the degree of nasal congestion and how
      comfortable each of the 2 measures was. In total, 136 measurements were
      evaluated. SUBJECTS: Seventy subjects were included in the study. All had a
      normal otorhinolaryngologic status with no acute or chronic infections.
      INTERVENTIONS: Nasal provocation tests with allergens, histamine, control
      solution, or xylometazoline were performed. MAIN OUTCOME MEASURES: Congestion or
      decongestion of the nasal mucosa was measured via nasal resistance (RMM), changes
      in light absorption of the nasal tissue (ORM), and visual analog scale. RESULTS:
      When comparing the relative change in light extinction in ORM with nasal airflow
      in RMM, we found correlation coefficients up to r = -0.69. Results from RMM were
      correlated with the subjects' ratings of nasal congestion (r = -0.63). In
      comparison, the correlation coefficient between these ratings and ORM was r =
      0.84. In addition, ORM was rated to be more comfortable than RMM. CONCLUSIONS:
      The subjects' ratings of nasal congestion correlated to a higher degree with the
      results from ORM than with those from RMM. In addition, ORM was rated as more
      comfortable than RMM. Overall, ORM appeared to be a valid technique for the
      assessment of changes in nasal congestion.

PMID- 17438249
TI  - Construct validity of the endoscopic sinus surgery simulator: II. Assessment of
      discriminant validity and expert benchmarking.
AB  - OBJECTIVES: To establish discriminant validity of the endoscopic sinus surgery
      simulator (ES3) (Lockheed Martin, Akron, Ohio) between various health care
      provider experience levels and to define benchmarking criteria for skills
      assessment. DESIGN: Prospective multi-institutional comparison study. SETTING:
      University-based tertiary care institution. PARTICIPANTS: Ten expert
      otolaryngologists, 14 otolaryngology residents, and 10 medical students.
      INTERVENTIONS: Subjects completed the ES3's virtual reality curriculum (10 novice
      mode, 10 intermediate mode, and 3 advanced mode trials). Performance scores were
      recorded on each trial. Performance differences were analyzed using analysis of
      variance for repeated measures (experience level as between-subjects factor).
      MAIN OUTCOME MEASURES: Simulator performance scores, accuracy, time to
      completion, and hazard disruption. RESULTS: The novice mode accurately
      distinguished the 3 groups, particularly at the onset of training (mean scores:
      senior otolaryngologists, 66.0; residents, 42.7; students, 18.3; for the paired
      comparisons between groups 1 and 2 and groups 1 and 3, P = .04 and .03,
      respectively). Subjects were not distinguished beyond trial 5. The intermediate
      mode only discriminated students from other subjects (P = .008). The advanced
      mode did not show performance differences between groups. Scores on the novice
      mode predicted those on the intermediate mode, which predicted advanced mode
      scores (r = 0.687), but no relationship was found between novice and advanced
      scores. All groups performed equally well and with comparable consistency at the
      outset of training. Expert scores were used to define benchmark criteria of
      optimal performance. CONCLUSIONS: This study completes the construct validity
      assessment of the ES3 by demonstrating its discriminant capabilities. It
      establishes expert surgeon benchmark performance criteria and shows that the ES3
      can train novice subjects to attain those. The refined analysis of trial
      performance scores could serve educational and skills assessment purposes.
      Current studies are evaluating the transfer of surgical skills acquired on the
      ES3 to the operating room (predictive validity).

PMID- 17438250
TI  - Graded carbon dioxide laser-induced subglottic injury in the rabbit model.
AB  - OBJECTIVE: To conduct an endoscopic and histologic analysis of the subglottic
      effects of various carbon dioxide laser-induced injuries in the rabbit model.
      DESIGN: Animals were assigned to either a control (cricothyroidotomy only) group
      or 4 (cricothyroidotomy and posterior subglottic laser) groups that were injured
      using varying systematically controlled carbon dioxide laser power exposures (5
      W, 8 W, and 12 W), with durations of 2 or 4 seconds, and surface area exposures
      (25% or 40%). SUBJECTS: Twenty-seven New Zealand white rabbits. INTERVENTIONS:
      The subglottis was approached via cricothyroidotomy. Control airways were
      immediately closed, while injured airways were subjected to graded carbon dioxide
      laser exposures prior to closure. Airways were endoscopically monitored
      preoperatively, immediately postoperatively, and on postoperative days 1, 7, 14,
      and 21, after which the animals were humanely killed and subglottic tissue
      harvested for histological evaluation. RESULTS: Clinical observation revealed no
      significantly obstructive (acute) stenosis during the duration of the study.
      Endoscopic visualization revealed the formation of posterior subglottic scarring.
      Histological analysis of the mucosa revealed that use of carbon dioxide laser
      resulted in a statistically significant (unpaired, 2-tailed t test, P<.05)
      proportional thickening of the lamina propria layer, without significant changes
      in the epithelial and cartilaginous layers. In addition, mucosal blood vessel
      size increased proportional to the power of the laser delivered to the area
      (P<.05). CONCLUSIONS: Carbon dioxide laser-induced injury to the subglottis
      caused localized scarring, lamina propria thickening, and increased vascularity,
      which resolved with time and was not associated with significant airway
      obstruction. This model describes a systematic, controlled, and reproducible
      method of investigating subglottic injury.

PMID- 17438251
TI  - Elucidating the role of interleukin 1beta and prostaglandin E2 in upper airway
      mucosal wound healing.
AB  - OBJECTIVES: To determine whether (1) inflammatory mediators IL-1beta (interleukin
      1beta) and prostaglandin E2 (PGE2) in mucosal secretions correlate with
      subglottic mucosal injury; and (2) mucosal fibroblasts contribute to PGE2
      production during mucosal healing. DESIGN: The subglottic mucosa in rabbits was
      wounded by means of varied carbon dioxide laser power and duration. Subglottic
      fibroblasts were exposed to IL-1beta and assayed for production of PGE2.
      SUBJECTS: Thirty-eight New Zealand white rabbits were used. Fibroblasts from
      normal and pathologic human subglottic tissues were grown in culture.
      INTERVENTIONS: Subglottic injury was established in 29 rabbits, and 9 rabbits
      were sham-wounded. Subglottic mucosal secretions were collected at baseline and
      days 1, 3, 7, 14, and 21 postoperatively and assayed for IL-1beta and PGE2 by
      enzyme-linked immunosorbent assay. Tissue was analyzed using quantitative
      polymerase chain reaction. Fibroblast cultures were exposed to IL-1beta and
      analyzed for PGE2 and its synthetic enzymes. RESULTS: Subglottic injury was
      associated with increased levels of IL-1beta and PGE2 in secretions. More
      extensive mucosal injury resulted in higher PGE2 levels at earlier times. Levels
      of IL-1beta were maximal after lesser damage. Expression of IL-beta and cyclo
      oxygenase 2 was elevated after mucosal injury. Fibroblast treatment with IL-1beta
      resulted in translocation of nuclear factor kappaB, up-regulation of PGE2
      synthetic enzymes, and increased production of endogenous PGE2. CONCLUSIONS:
      Mucosal injury is associated with up-regulation of inflammatory genes and
      parallel increases in secretion levels of IL-1beta and PGE2, key mediators of
      inflammation and healing. Subglottic mucosal fibroblasts are a potential source
      of inflammatory mediators after injury or other trauma.

PMID- 17438252
TI  - Synchronous airway lesions and esophagitis in young patients undergoing
      adenoidectomy.
AB  - OBJECTIVE: To determine the prevalence of synchronous airway lesions and
      esophagitis in children younger than 18 months undergoing adenoidectomy for
      adenoid hypertrophy and upper airway obstruction. DESIGN: Retrospective review
      spanning 4.5 years. SETTING: Tertiary care children's hospital. PATIENTS: All
      children younger than 18 months who underwent adenoidectomy for upper airway
      obstruction by 2 pediatric otolaryngologists. EXCLUSION CRITERIA: craniofacial
      dysmorphism and congenital syndromes. INTERVENTIONS: Simultaneous interventions
      during adenoidectomy included flexible nasopharyngolaryngoscopy (n = 32), direct
      laryngoscopy (n = 31), rigid tracheobronchoscopy (n = 30), and esophagoscopy with
      biopsy (n = 32). MAIN OUTCOME MEASURES: Prevalence of synchronous airway lesions
      and histologic esophagitis. RESULTS: Thirty-five children younger than 18 months
      underwent adenoidectomy for airway obstruction (2 also had simultaneous
      tonsillectomy). Synchronous airway lesions were found in 19 (59%) of 32 patients
      who underwent airway endoscopy, including laryngeal edema (n = 9), laryngomalacia
      (n = 8), tracheal vascular compression (n = 4), subglottic stenosis (n = 4),
      midmembranous vocal fold lesions (n = 3), bronchial stenosis (n = 1), and true
      vocal fold immobility (n = 1). Among 32 patients who underwent esophageal biopsy,
      histologic evidence of gastroesophageal reflux disease was found in 10 patients
      (31%), and eosinophilic esophagitis was found in 4 patients (13%). Overall
      prevalence of any synchronous finding (airway and/or esophagus) was 27 (77%) of
      35. CONCLUSIONS: Synchronous airway lesions and esophagitis (both
      gastroesophageal reflux disease and eosinophilic esophagitis) were prevalent
      among children younger than 18 months undergoing adenoidectomy for adenoid
      hypertrophy and upper airway obstruction. The presence of these findings argues
      for consideration of endoscopy during adenoidectomy for very young children.

PMID- 17438253
TI  - Relationship between pediatric obesity and otitis media with effusion.
AB  - OBJECTIVE: To investigate the relationship between pediatric otitis media with
      effusion and obesity, as determined by body mass index (BMI) (calculated as
      weight in kilograms divided by height in meters squared) and serum triglyceride
      (TG) and total cholesterol (TC) concentrations. DESIGN: A prospective,
      nonrandomized, case-control study. SETTING: University-affiliated hospital.
      SUBJECTS: The experimental group comprised 155 children aged 2 to 7 years, who
      received unilateral or bilateral ventilation tube insertion for the treatment of
      otitis media with effusion. The control group comprised 118 children with no
      history of otitis media with effusion, who underwent operations for conditions
      other than ear diseases. Based on BMI and serum TG and TC concentrations, we
      divided the experimental group into 2 subgroups, those who were and were not
      obese. MAIN OUTCOME MEASURES: We determined the difference between the
      experimental and control groups in BMI and serum TG and TC concentrations and the
      difference between the obese and nonobese subgroups in frequency of ventilation
      tube insertion. RESULTS: Mean +/- SD BMI (22.0 +/- 3.4 vs 16.3 +/- 2.4) (P = .01)
      and mean +/- SD TC level (195.0 +/- 31.0 mg/dL vs 159.3 +/- 26.9 mg/dL [5.05 +/-
      0.80 mmol/L vs 4.13 +/- 0.70 mmol/L]) (P = .04), but not mean serum TG level
      (109.4 +/- 40.4 mg/dL vs 90.0 +/- 52.3 mg/dL [1.24 +/- 0.46 mmol/L vs 1.02 +/-
      0.59 mmol/L]) (P = .13), were significantly higher in the experimental group than
      in the control group. Frequency of ventilation tube insertion, however, did not
      differ significantly between the obese and nonobese subgroups, whether divided by
      BMI (P = .10) or serum TG (P = .12) or TC (P = .07) concentration. CONCLUSION:
      Childhood obesity may be associated with the occurrence of otitis media with
      effusion.

PMID- 17438254
TI  - Recovery of dynamic visual acuity in bilateral vestibular hypofunction.
AB  - OBJECTIVE: To determine the effect of vestibular exercises on the recovery of
      visual acuity during head movement in patients with bilateral vestibular
      hypofunction (BVH). DESIGN: Prospective, randomized, double-blinded study.
      SETTING: Outpatient clinic, academic setting. PATIENTS: Thirteen patients with
      BVH, aged 47 to 73 years. INTERVENTION: One group (8 patients) performed
      vestibular exercises designed to enhance remaining vestibular function, and the
      other (5 patients) performed placebo exercises. MAIN OUTCOME MEASURES:
      Measurements of dynamic visual acuity (DVA) during predictable head movements
      using a computerized test; measurement of intensity of oscillopsia using a visual
      analog scale. RESULTS: As a group, patients who performed vestibular exercises
      showed a significant improvement in DVA (P = .001), whereas those performing
      placebo exercises did not (P = .07). Only type of exercise (ie, vestibular vs
      placebo) was significantly correlated with change in DVA. Other factors examined,
      including age, time from onset, initial DVA, and complaints of oscillopsia and
      disequilibrium, were not significantly correlated with change in DVA. Change in
      oscillopsia did not correlate with change in DVA. CONCLUSIONS: Use of vestibular
      exercises is the main factor involved in recovery of DVA in patients with BVH. We
      theorize that exercises may foster the use of centrally programmed eye movements
      that could substitute for the vestibulo-ocular reflex. TRIAL REGISTRATION:
      clinicaltrials.gov Identifier: NCT00411216.

PMID- 17438255
TI  - Relief of idiopathic subjective tinnitus: is gabapentin effective?
AB  - OBJECTIVE: To assess the therapeutic benefit of gabapentin (Neurontin) for
      subjective idiopathic troublesome tinnitus. DESIGN: An 8-week, double-blind,
      randomized clinical trial. SETTING: Academic otolaryngology clinic in St Louis,
      Mo. SUBJECTS: One hundred thirty-five subjects with severe idiopathic subjective
      tinnitus of 6 months' duration or longer. INTERVENTION: Gabapentin, at a
      maintenance dosage of 900 to 3600 mg/d for 8 weeks, or lactose placebo. MAIN
      OUTCOME MEASURE: Change in the Tinnitus Handicap Inventory score from baseline to
      the study end point. RESULTS: The overall change in the Tinnitus Handicap
      Inventory score for the entire cohort from baseline to week 8 was 11.2; the
      change among the 59 subjects randomized to the gabapentin arm was 11.3 and the
      change among the 56 subjects in the placebo arm was 11.0. The difference was 0.03
      (95% confidence interval, -5.5 to 6.2; P = .91). CONCLUSION: Gabapentin is no
      more effective than placebo for the relief of idiopathic subjective tinnitus.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00317850.

PMID- 17438256
TI  - Intramuscular myxoma presenting as a rare posterior neck mass in a young child:
      case report and literature review.
AB  - Intramuscular myxoma (IMM) is an uncommon benign tumor that presents as a slow
      growing, deep-seated mass confined to the skeletal muscle. Histologically, these
      lesions most resemble umbilical cord tissue. They are generally found in the
      proximal thigh, gluteal region, or shoulder girdle and are exceedingly rare neck
      masses in the pediatric population. These tumors most often present as painless,
      deep-seated intramuscular masses that may exhibit symptoms of compression of
      surrounding structures.(1) I report a case of a 22-month-old girl with an IMM in
      the posterior cervical triangle.

PMID- 17438257
TI  - Mycotic pseudoaneurysm of the internal maxillary artery: case report and review
      of the literature.
AB  - Pseudoaneurysms of the internal maxillary artery are rare entities that are most
      commonly caused by trauma. Herein we report a novel case of an internal maxillary
      artery pseudoaneurysm of infectious etiology and discuss the diagnosis and
      treatment of this disease.

PMID- 17438258
TI  - Radiology quiz case 1. Schwannoma of the trigeminal nerve in the pterygopalatine
      fossa.

PMID- 17438259
TI  - Radiology quiz case 2. Organized hematoma of the maxillary sinus.

PMID- 17438260
TI  - Pathology quiz case 1. Actinomycosis of the lip mimicking minor salivary gland
      tumor.

PMID- 17438261
TI  - Pathology quiz case 2. Myxoma of the frontal sinus.

PMID- 17438262
TI  - Pathology quiz case 3. Kikuchi-Fujimoto disease.

PMID- 17438263
TI  - Mouse neutrophilic granulocytes express mRNA encoding the macrophage colony
      stimulating factor receptor (CSF-1R) as well as many other macrophage-specific
      transcripts and can transdifferentiate into macrophages in vitro in response to
      CSF-1.
AB  - The differentiation of macrophages from their progenitors is controlled by
      macrophage colony-stimulating factor (CSF-1), which binds to a receptor (CSF-1R)
      encoded by the c-fms proto-oncogene. We have previously used the promoter region
      of the CSF-1R gene to direct expression of an enhanced green fluorescent protein
      (EGFP) reporter gene to resident macrophage populations in transgenic mice. In
      this paper, we show that the EGFP reporter is also expressed in all granulocytes
      detected with the Gr-1 antibody, which binds to Ly-6C and Ly-6G or with a Ly-6G
      specific antibody. Transgene expression reflects the presence of CSF-1R mRNA but
      not CSF-1R protein. The same pattern is observed with the macrophage-specific
      F4/80 marker. Based on these findings, we performed a comparative array profiling
      of highly purified granulocytes and macrophages. The patterns of mRNA expression
      differed predominantly through granulocyte-specific expression of a small subset
      of transcription factors (Egr1, HoxB7, STAT3), known abundant granulocyte
      proteins (e.g., S100A8, S100A9, neutrophil elastase), and specific receptors
      (fMLP, G-CSF). These findings suggested that appropriate stimuli might mediate
      rapid interconversion of the major myeloid cell types, for example, in
      inflammation. In keeping with this hypothesis, we showed that purified Ly-6G
      positive granulocytes express CSF-1R after overnight culture and can subsequently
      differentiate to form F4/80-positive macrophages in response to CSF-1.

PMID- 17438264
TI  - Role of group-conserved residues in the helical core of beta2-adrenergic
      receptor.
AB  - G protein-coupled receptors (GPCRs) belonging to class A contain several highly
      conserved (>90%) amino acids in their transmembrane helices. Results of
      mutational studies of these highly conserved residues suggest a common mechanism
      for locking GPCRs in an inactive conformation and for their subsequent activation
      upon ligand binding. Recently, a second set of sites in the transmembrane helices
      has been identified in which amino acids with small side chains, such as Gly,
      Ala, Ser, Thr, and Cys, are highly conserved (>90%) when considered as a group.
      These group-conserved residues have not been recognized as having essential
      structural or functional roles. To determine the role of group-conserved residues
      in the beta(2)-adrenergic receptor (beta(2)-AR), amino acid replacements guided
      by molecular modeling were carried out at key positions in transmembrane helices
      H2-H4. The most significant changes in receptor expression and activity were
      observed upon replacement of the amino acids Ser-161 and Ser-165 in H4.
      Substitution at these sites by larger residues lowered the expression and
      activity of the receptor but did not affect specific binding to the antagonist
      ligand dihydroalprenolol. A second site mutation, V114A, rescued the low
      expression of the S165V mutant. Substitution of other group-conserved residues in
      H2-H4 by larger amino acids lowered receptor activity in the order Ala-128, Ala
      76, Ser-120, and Ala-78. Together these data provide comprehensive analysis of
      group-conserved residues in a class A GPCR and allow insights into the roles of
      these residues in GPCR structure and function.

PMID- 17438265
TI  - Four domains of p300 each bind tightly to a sequence spanning both
      transactivation subdomains of p53.
AB  - The transcriptional coactivator p300 binds to and mediates the transcriptional
      functions of the tetrameric tumor suppressor p53. Both proteins consist of
      independently folded domains linked by intrinsically disordered sequences. A well
      studied short sequence of the p53 transactivation domain, p53(15-29), binds
      weakly to four folded domains of p300 [Taz1/cysteine-histidine-rich region 1
      (CH1), Kix, Taz2/CH3, IBiD], with dissociation constants (K(D)) in the 100 muM
      region. However, we found that a longer N-terminal transactivation domain
      construct p53(1-57) bound tightly to each p300 domain. Taz2/CH3 had the greatest
      affinity (K(D) = 27 nM) and competes with the N-terminal domain of Mdm2 for the
      p53 N terminus. p300 thus can protect the N terminus of p53 against the binding
      of other proteins. Mutations of p53 that abrogate transactivation (L22Q/W23S,
      W53Q/F54S) greatly weakened binding to each p300 domain, linking phenotypic
      defects to weakened coactivator binding. We propose a complex between tetrameric
      p53 and p300 in which four domains of p300 wrap around the four transactivation
      domains of p53.

PMID- 17438266
TI  - Environmental effects on parasitic disease transmission exemplified by
      schistosomiasis in western China.
AB  - Environmental effects on the transmission of many parasitic diseases are well
      recognized, but the role of specific factors like climate and agricultural
      practices in modulating transmission is seldom characterized quantitatively.
      Based on studies of Schistosoma japonicum transmission in irrigated agricultural
      environments in western China, a mathematical model was used to quantify
      environmental impacts on transmission intensity. The model was calibrated by
      using field data from intervention studies in three villages and simulated to
      predict the effects of alternative control options. Both the results of these
      interventions and earlier epidemiological findings confirm the central role of
      environmental factors, particularly those relating to snail habitat and
      agricultural and sanitation practices. Moreover, the findings indicate the
      inadequacy of current niclosamide-praziquantel strategies alone to achieve
      sustainable interruption of transmission in some endemic areas. More generally,
      the analysis suggests a village-specific index of transmission potential and how
      this potential is modulated by time-varying factors, including climatological
      variables, seasonal water-contact patterns, and irrigation practices. These time
      variable factors, a village's internal potential, and its connectedness to its
      neighbors provide a framework for evaluating the likelihood of sustained
      schistosomiasis transmission and suggest an approach to quantifying the role of
      environmental factors for other parasitic diseases.

PMID- 17438268
TI  - An instrument for direct observations of seismic and normal-mode rotational
      oscillations of the Earth.
AB  - The rotations around the vertical axis associated with the normal mode
      oscillations of the Earth and those induced by the seismic and other disturbances
      have been very difficult to observe directly. Such observations will provide
      additional information for 3D modeling of the Earth and for understanding
      earthquakes and other underground explosions. In this paper, we describe the
      design of an instrument capable of measuring the rotational motions associated
      with the seismic oscillations of the Earth, including the lowest frequency normal
      mode at nu approximately 3.7 x 10(-4) Hz. The instrument consists of a torsion
      balance with a natural frequency of nu(0) approximately 1.6 x 10(-4) Hz, which is
      observed by an autocollimating optical lever of high angular resolution and
      dynamic range. Thermal noise limits the sensitivity of the apparatus to
      amplitudes of approximately 1.5 x 10(-9) rad at the lowest frequency normal mode
      and the sensitivity improves as nu(-3/2) with increasing frequency. Further
      improvements in sensitivity by about two orders of magnitude may be achieved by
      operating the balance at cryogenic temperatures. Alternatively, the instrument
      can be made more robust with a reduced sensitivity by increasing nu(0) to
      approximately 10(-2) Hz. This instrument thus complements the ongoing effort by
      Igel and others to study rotational motions using ring laser gyroscopes and
      constitutes a positive response to the clarion call for developments in rotation
      seismology by Igel, Lee, and Todorovska [H. Igel, W.H.K. Lee and M.I. Todorovska,
      AGU Fall Meeting 2006, Rotational Seismology Sessions: S22A,S23B, Inauguration of
      the International Working Group on Rotational Seismology (IWGoRS)].

PMID- 17438267
TI  - The dynein light chain 8 binding motif of rabies virus phosphoprotein promotes
      efficient viral transcription.
AB  - Recent studies indicate that the interaction between rabies virus (RV)
      phosphoprotein and the dynein light chain 8 (LC8) is essential for RV
      pathogenesis. Through its association with the dynein motor complex, LC8 has been
      suggested as a molecular factor that links the viral ribonucleoprotein to the
      host cell transport system. Recent structural investigations, however, dispute
      this model. To understand the role of LC8 in RV pathogenesis, we generated
      recombinant RVs with or without the LC8 binding domain (LC8-BD) deleted from the
      RV phosphoprotein. Peripheral infection of adult mice showed that removal of the
      LC8-BD did not inhibit entry into the CNS, although it prevented onset of RV
      induced CNS disease. However, deletion of the LC8-BD significantly attenuated
      viral transcription and replication in the CNS. Studies in RAG2 knockout (KO)
      mice infected with the same recombinant RVs confirmed this finding and indicated
      that the adaptive immune system is not a factor in the attenuation of viral
      replication early in the infection. In cell culture, the deletion of the LC8-BD
      greatly attenuated growth on neuronal cells whereas the growth pattern on
      nonneuronal cells remained unchanged. However, deletion of the LC8-BD did not
      affect production of RV virions. We provide evidence that removal of the LC8-BD
      decreases primary transcription. In this study, we propose that LC8 does not play
      a role in the retrograde axonal transport of RV and that the deletion of the LC8
      BD impairs the infectivity of the virions by reducing early transcription and
      replication in neurons.

PMID- 17438269
TI  - Complex spatial group patterns result from different animal communication
      mechanisms.
AB  - We present previously undescribed spatial group patterns that emerge in a one
      dimensional hyperbolic model for animal group formation and movement. The
      patterns result from the assumption that the interactions governing movement
      depend not only on distance between conspecifics, but also on how individuals
      receive information about their neighbors and the amount of information received.
      Some of these patterns are classical, such as stationary pulses, traveling waves,
      ripples, or traveling trains. However, most of the patterns have not been
      reported previously. We call these patterns zigzag pulses, semizigzag pulses,
      breathers, traveling breathers, and feathers.

PMID- 17438270
TI  - Bacteriophage N4 virion RNA polymerase interaction with its promoter DNA hairpin.
AB  - Bacteriophage N4 minivirion RNA polymerase (mini-vRNAP), the RNA polymerase
      (RNAP) domain of vRNAP, is a member of the T7-like RNAP family. Mini-vRNAP
      recognizes promoters that comprise conserved sequences and a 3-base loop-5-base
      pair (bp) stem DNA hairpin structure on single-stranded templates. Here, we
      defined the DNA structural and sequence requirements for mini-vRNAP promoter
      recognition. Mini-vRNAP binds a 20-nucleotide (nt) N4 P2 promoter
      deoxyoligonucleotide with high affinity (K(d) = 2 nM) to form a salt-resistant
      complex. We show that mini-vRNAP interacts specifically with the central base of
      the hairpin loop (-11G) and a base at the stem (-8G) and that the guanine 6-keto
      and 7-imino groups at both positions are essential for binding and complex salt
      resistance. The major determinant (-11G), which must be presented to mini-vRNAP
      in the context of a hairpin loop, appears to interact with mini-vRNAP Trp-129.
      This interaction requires template single-strandedness at positions -2 and -1.
      Contacts with the promoter are disrupted when the RNA product becomes 11-12 nt
      long. This detailed description of vRNAP interaction with its promoter hairpin
      provides insights into RNAP-promoter interactions and explains how the injected
      vRNAP, which is present in one or two copies, recognizes its promoters on a
      single copy of the injected genome.

PMID- 17438271
TI  - Accumulation of NFAT mediates IL-2 expression in memory, but not naive, CD4+ T
      cells.
AB  - In contrast to naive CD4+ T cells, memory CD4+ T cells rapidly express high
      levels of effector cytokines in response to antigen stimulation. The molecular
      mechanism for this specific behavior is not well understood. The nuclear factor
      of activated T cells (NFAT) family of transcription factors plays an important
      role in the transcription of many cytokine genes. Here we show that memory CD4+ T
      cells rapidly induce NFAT-mediated transcription upon T cell receptor ligation
      whereas NFAT activation in naive CD4+ T cells requires longer periods of
      stimulation. The difference in kinetics correlates with the low levels of NFATc1
      and NFATc2 proteins present in naive CD4+ T cells and their high levels in memory
      CD4+ T cells. Accordingly, IL-2 expression requires NFAT activation only in
      memory CD4+ T cells whereas it is NFAT-independent in naive CD4+ T cells. Thus,
      the accumulation of NFATc1 and NFATc2 in memory CD4+ T cells represents a
      previously uncharacterized regulatory mechanism for the induction of early gene
      expression after antigen stimulation.

PMID- 17438272
TI  - Cyanobacterial clock, a stable phase oscillator with negligible intercellular
      coupling.
AB  - Accuracy in cellular function has to be achieved despite random fluctuations
      (noise) in the concentrations of different molecular constituents inside and
      outside the cell. The circadian oscillator in cyanobacteria is an example of
      resilience to noise. This resilience could be either the consequence of
      intercellular communication or the intrinsic property of the built-in biochemical
      network. Here we investigate the intercellular coupling hypothesis. A short
      theoretical depiction of interacting noisy phase oscillators, confirmed by
      numerical simulations, allows us to discriminate the effect of coupling from
      noise. Experimentally, by studying the phase of concurrent populations of
      different initial phases, we evaluate a very small upper limit of the
      intercellular coupling strength. In addition, in situ entrainment experiments
      confirm our ability to detect a coupling of the circadian oscillator to an
      external force and to describe explicitly the dynamic change of the mean phase.
      We demonstrate, therefore, that the cyanobacterial clock stability is a built-in
      property as the intercellular coupling effect is negligible.

PMID- 17438273
TI  - Borrelia burgdorferi intercepts host hormonal signals to regulate expression of
      outer surface protein A.
AB  - The Borrelia burgdorferi infectious cycle requires that the organism adapt to
      vast differences in environmental conditions found in its tick and mammalian
      hosts. Previous studies have shown that B. burgdorferi accomplishes this
      accommodation in part by regulating expression of its surface proteins. Outer
      surface protein A (OspA) is a borrelial protein important in colonization of the
      tick midgut. OspA is up-regulated when the organism is in its tick host and down
      regulated when it is in a mammalian host. However, little is known about how it
      is up-regulated again in a mammalian host in preparation for entry into a feeding
      tick. Here, we report that the host neuroendocrine stress hormones, epinephrine
      and norepinephrine, are specifically bound by B. burgdorferi and result in
      increased expression of OspA. This recognition is specific and blocked by
      competitive inhibitors of human adrenergic receptors. To determine whether
      recognition of catecholamines, which are likely to be present at the site of a
      tick bite, may play a role in preparing the organism for reentry into a tick from
      a mammalian host, we administered a beta-adrenergic blocker, propranolol, to
      infected mice. Propranolol significantly reduced uptake of B. burgdorferi by
      feeding ticks and decreased expression of OspA in B. burgdorferi recovered from
      ticks that fed on propranolol-treated mice. Our studies suggest that B.
      burgdorferi may co-opt host neuroendocrine signals to inform the organism of
      local changes that predict the presence of its next host and allow it to prepare
      for transition to a new environment.

PMID- 17438274
TI  - Using theory and computation to model nanoscale properties.
AB  - This article provides an overview of the use of theory and computation to
      describe the structural, thermodynamic, mechanical, and optical properties of
      nanoscale materials. Nanoscience provides important opportunities for theory and
      computation to lead in the discovery process because the experimental tools often
      provide an incomplete picture of the structure and/or function of nanomaterials,
      and theory can often fill in missing features crucial to understanding what is
      being measured. However, there are important challenges to using theory as well,
      as the systems of interest are usually too large, and the time scales too long,
      for a purely atomistic level theory to be useful. At the same time, continuum
      theories that are appropriate for describing larger-scale (micrometer) phenomena
      are often not accurate for describing the nanoscale. Despite these challenges,
      there has been important progress in a number of areas, and there are exciting
      opportunities that we can look forward to as the capabilities of computational
      facilities continue to expand. Some specific applications that are discussed in
      this paper include: self-assembly of supramolecular structures, the thermal
      properties of nanoscale molecular systems (DNA melting and nanoscale water
      meniscus formation), the mechanical properties of carbon nanotubes and diamond
      crystals, and the optical properties of silver and gold nanoparticles.

PMID- 17438275
TI  - Derepression of the NC80 motif is critical for the photoactivation of Arabidopsis
      CRY2.
AB  - Cryptochromes are blue light receptors that regulate photomorphogenesis in plants
      and the circadian clock in animals and plants. Arabidopsis cryptochrome 2 (CRY2)
      mediates blue light inhibition of hypocotyl elongation and photoperiodic control
      of floral initiation. CRY2 undergoes blue light-induced phosphorylation, which
      was hypothesized to be associated with CRY2 photoactivation. To further
      investigate how light activates CRY2, we analyzed the physiological activities
      and phosphorylation of various CRY2 fusion proteins in transgenic plants. Our
      results showed that an 80-residue motif, referred to as NC80, was sufficient to
      confer the physiological function of CRY2. The GUS-NC80 fusion protein expressed
      in transgenic plants is constitutively active but unphosphorylated, suggesting
      that the blue light-induced CRY2 phosphorylation causes a conformational change
      to derepress the NC80 motif. Consistent with this hypothesis, the CRY2 C-terminal
      tail was found to be required for the blue light-induced CRY2 phosphorylation but
      not for the CRY2 activity. We propose that the PHR domain and the C-terminal tail
      of the unphosphorylated CRY2 form a "closed" conformation to suppress the NC80
      motif in the absence of light. In response to blue light, the C-terminal tail of
      CRY2 is phosphorylated and electrostatically repelled from the surface of the PHR
      domain to form an "open" conformation, resulting in derepression of the NC80
      motif and signal transduction to trigger photomorphogenic responses.

PMID- 17438276
TI  - Intravesicular and intervesicular interaction by orthogonal multivalent host
      guest and metal-ligand complexation.
AB  - Host vesicles composed of amphiphilic beta-cyclodextrin CD1 recognize metal
      coordination complexes of the adamantyl-functionalized ethylenediamine ligand L
      via hydrophobic inclusion in the beta-cyclodextrin cavities at the vesicle
      surface. In the case of Cu(II) and L, the resulting coordination complex was
      exclusively CuL(2), and the interaction with the host vesicles was
      intravesicular, unless the concentration of metal complex and vesicles was high
      (>0.1 mM). In the case of Ni(II) and L, a mixture was formed consisting of mainly
      NiL and NiL(2), the interaction with the host vesicles was effectively
      intervesicular, and addition of the guest-metal complex resulted in aggregation
      of the vesicles into dense, multilamellar clusters even in dilute solution [1
      microM Ni(II)]. The metal-L complex could be eliminated by a strong chelator such
      as EDTA, and the intervesicular interaction could be suppressed by a competitor
      such as unmodified beta-cyclodextrin. The result from this investigation is that
      the strongest metal-coordination complex [Cu(II) with L] binds exclusively
      intravesicularly, whereas the weakest metal-coordination complex [Ni(II) with L]
      binds predominantly intervesicularly and is the strongest interfacial binder.
      These experimental observations are confirmed by a thermodynamic model that
      describes multivalent orthogonal interactions at interfaces.

PMID- 17438277
TI  - miR-150, a microRNA expressed in mature B and T cells, blocks early B cell
      development when expressed prematurely.
AB  - MicroRNAs (miRNAs) are a family of approximately 22-nt noncoding RNAs that can
      posttranscriptionally regulate gene expression. Several miRNAs are specifically
      expressed in hematopoietic cells. Here we show that one such miRNA, miR-150, is
      mainly expressed in the lymph nodes and spleen and is highly up-regulated during
      the development of mature T and B cells; expression of miR-150 is sharply up
      regulated at the immature B cell stage. Overexpression of miR-150 in
      hematopoietic stem cells, followed by bone marrow transplantation, had little
      effect on the formation of either mature CD8- and CD4-positive T cells or
      granulocytes or macrophages, but the formation of mature B cells was greatly
      impaired. Furthermore, premature expression of miR-150 blocked the transition
      from the pro-B to the pre-B stage. Our results indicate that miR-150 most likely
      down-regulates mRNAs that are important for pre- and pro-B cell formation or
      function, and its ectopic expression in these cells blocks further development of
      B cells.

PMID- 17438278
TI  - Network of general and specialty J protein chaperones of the yeast cytosol.
AB  - J proteins are obligate cochaperones of Hsp70s, stimulating their ATPase activity
      and thus allowing them to function in multiple cellular processes. In most
      cellular compartments, an Hsp70 works with multiple, structurally divergent J
      proteins. To better understand the functional specificity of J proteins and the
      complexity of the Hsp70:J protein network, we undertook a comprehensive analysis
      of 13 J proteins of the cytosol of the yeast Saccharomyces cerevisiae. Phenotypes
      caused by the absence of four proteins, Sis1, Jjj1, Jjj3, and Cwc23, could not be
      rescued by overexpression of any other cytosolic J protein, demonstrating the
      distinctive nature of J proteins. In one case, that of Zuo1, the phenotypic
      effects of the absence of a J protein could be rescued by overexpression of only
      one other J protein, Jjj1, which, like Zuo1, is ribosome-associated. In contrast,
      the severe growth phenotype caused by the absence of the cytosol's most abundant
      J protein, Ydj1, was substantially rescued by expression of J domain-containing
      fragments of many cytosolic J proteins. We conclude that many functions of Hsp70
      chaperone machineries only require stimulation of Hsp70's ATPase activity by J
      protein partners. However, a subset of Hsp70 functions requires specific J
      protein partners, likely demanding either sublocalization within the compartment
      or binding to specific client proteins.

PMID- 17438280
TI  - Evolutionary dynamics of olfactory receptor genes in Drosophila species.
AB  - Olfactory receptor (OR) genes are of vital importance for animals to find food,
      identify mates, and avoid dangers. In mammals, the number of OR genes is large
      and varies extensively among different orders, whereas, in insects, the extent of
      interspecific variation appears to be small, although only a few species have
      been studied. To understand the evolutionary changes of OR genes, we identified
      all OR genes from 12 Drosophila species, of which the evolutionary time is
      roughly equivalent to that of eutherian mammals. The results showed that all
      species examined have similar numbers ( approximately 60) of functional OR genes.
      Phylogenetic analysis indicated that the ancestral species also had similar
      numbers of genes, but there were frequent gains and losses of genes that occurred
      in each evolutionary lineage. It appears that tandem duplication and random
      inactivation of duplicate genes are the major factors of gene number change.
      However, chromosomal rearrangements have contributed to the establishment of
      genome-wide distribution of OR genes. These results suggest that the repertoire
      of OR genes in Drosophila has been quite stable compared with the mammalian
      genes. The difference in evolutionary pattern between Drosophila and mammals can
      be explained partly by the differences of gene expression mechanisms and partly
      by the environmental and behavioral differences.

PMID- 17438279
TI  - Gene expression in vivo shows that Helicobacter pylori colonizes an acidic niche
      on the gastric surface.
AB  - Helicobacter pylori is a gastric-dwelling pathogen responsible, with acid
      secretion, for peptic ulcer and a 20-fold increase in the risk of gastric cancer.
      Several transcriptomes have been described after short-term exposure to acidity
      in vitro, but there are no data identifying the effects of chronic gastric
      exposure on bacterial gene expression. Comparison of the in vivo to the in vitro
      transcriptome at pH 7.4 identified several groups of genes of known function that
      increased expression >2-fold, and three of these respond both to acidity in vitro
      and to gastric infection. Almost all known acid acclimation genes are highly up
      regulated. These include ureA, ureB, and rocF and the pH-gated urea channel,
      ureI. There is also up-regulation of two groups of motility and chemotaxis genes
      and for pathogenicity island genes, especially cagA, a predictor for
      pathogenicity. Most of these genes interact with HP0166, the response element of
      the pH-sensing two-component histidine kinase, HP0165/HP0166, ArsRS. Based on the
      pH profile of survival of ureI deletion mutants in vitro and their inability to
      survive in gastric acidity, the habitat of the organism at the gastric surface is
      acidic with a pH < or = 4.0. Hence, the pH of the habitat of H. pylori on the
      surface of the stomach largely determines the regulation of these specific groups
      of genes.

PMID- 17438281
TI  - Chimaerin and Rac regulate cell number, adherens junctions, and ERK MAP kinase
      signaling in the Drosophila eye.
AB  - The chimaerin family of Rac GTPase-activating proteins (GAPs) has been implicated
      in neural development and tumor progression, although the cellular mechanisms of
      their effects are poorly understood. To study their physiologic function, we used
      the Drosophila retina as a model system. Reduced expression of the fly chimaerin
      ortholog RhoGAP5a in the pupal eye led to an excess of interommatidial pigment
      cells, aberrant cell contacts, and an increase in activated ERK that localized
      specifically to the plasma membrane. Reducing RhoGAP5A levels suppressed the
      effects of disrupted EGF receptor signaling. Perturbation of Rac activity led to
      similar phenotypes, whereas coexpression of Rac and RhoGAP5A-dsRNAi resulted in
      the elimination of adherens junctions between interommatidial cells. Our results
      reveal a role for chimaerin in the regulation of ERK signaling and cell-cell
      adhesion and have implications for its participation in epithelial development
      and tumor progression.

PMID- 17438282
TI  - Reevolution of sexuality breaks Dollo's law.
AB  - The dominance of sexual reproduction is still an unresolved enigma in
      evolutionary biology. Strong advantages of sex have to exist, because only a few
      parthenogenetic taxa persist over evolutionary timescales. Oribatid mites (Acari)
      include outstanding exceptions to the rule that parthenogenetically reproducing
      taxa are of recent origin and doomed to extinction. In addition to the existence
      of large parthenogenetic clusters in oribatid mites, phylogenetic analyses of
      this study and model-based reconstruction of ancestral states of reproduction
      imply that Crotoniidae have reevolved sexuality from parthenogenetic ancestors
      within one of those clusters. This reversal in reproductive mode is unique in the
      animal kingdom and violates Dollo's law that complex ancestral states can never
      be reacquired. The reevolution of sexuality requires that ancestral genes for
      male production are maintained over evolutionary time. This maintenance likely is
      true for oribatid mites because spanandric males exist in various species,
      although mechanisms that enable the storage of genetically ancestral traits are
      unclear. Our findings present oribatid mites as a unique model system to explore
      the evolutionary significance of parthenogenetic and sexual reproduction.

PMID- 17438283
TI  - Resveratrol stimulates AMP kinase activity in neurons.
AB  - Resveratrol is a polyphenol produced by plants that has multiple beneficial
      activities similar to those associated with caloric restriction (CR), such as
      increased life span and delay in the onset of diseases associated with aging. CR
      improves neuronal health, and the global beneficial effects of CR have been
      postulated to be mediated by the nervous system. One key enzyme thought to be
      activated during CR is the AMP-activated kinase (AMPK), a sensor of cellular
      energy levels. AMPK is activated by increases in the cellular AMP:ATP ratio,
      whereupon it functions to help preserve cellular energy. In this regard, the
      regulation of dietary food intake by hypothalamic neurons is mediated by AMPK.
      The suppression of nonessential energy expenditure by activated AMPK along with
      the CR mimetic and neuroprotective properties of resveratrol led us to
      hypothesize that neuronal activation of AMPK could be an important component of
      resveratrol activity. Here, we show that resveratrol activated AMPK in Neuro2a
      cells and primary neurons in vitro as well as in the brain. Resveratrol and the
      AMPK-activating compound 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside
      (AICAR) promoted robust neurite outgrowth in Neuro2a cells, which was blocked by
      genetic and pharmacologic inhibition of AMPK. Resveratrol also stimulated
      mitochondrial biogenesis in an AMPK-dependent manner. Resveratrol-stimulated AMPK
      activity in neurons depended on LKB1 activity but did not require the NAD
      dependent protein deacetylase SIRT1 during this time frame. These findings
      suggest that neuronal activation of AMPK by resveratrol could affect neuronal
      energy homeostasis and contribute to the neuroprotective effects of resveratrol.

PMID- 17438284
TI  - Mechanism of the myosin catalyzed hydrolysis of ATP as rationalized by molecular
      modeling.
AB  - The intrinsic chemical reaction of adenosine triphosphate (ATP) hydrolysis
      catalyzed by myosin is modeled by using a combined quantum mechanics and
      molecular mechanics (QM/MM) methodology that achieves a near ab initio
      representation of the entire model. Starting with coordinates derived from the
      heavy atoms of the crystal structure (Protein Data Bank ID code 1VOM) in which
      myosin is bound to the ATP analog ADP.VO(4)(-), a minimum-energy path is found
      for the transformation ATP + H(2)O --> ADP + P(i) that is characterized by two
      distinct events: (i) a low activation-energy cleavage of the P(gamma)
      O(betagamma) bond and separation of the gamma-phosphate from ADP and (ii) the
      formation of the inorganic phosphate as a consequence of proton transfers
      mediated by two water molecules and assisted by the Glu-459-Arg-238 salt bridge
      of the protein. The minimum-energy model of the enzyme-substrate complex features
      a stable hydrogen-bonding network in which the lytic water is positioned
      favorably for a nucleophilic attack of the ATP gamma-phosphate and for the
      transfer of a proton to stably bound second water. In addition, the P(gamma)
      O(betagamma) bond has become significantly longer than in the unbound state of
      the ATP and thus is predisposed to cleavage. The modeled transformation is viewed
      as the part of the overall hydrolysis reaction occurring in the closed enzyme
      pocket after ATP is bound tightly to myosin and before conformational changes
      preceding release of inorganic phosphate.

PMID- 17438285
TI  - Terrestrial-style feeding in a very early aquatic tetrapod is supported by
      evidence from experimental analysis of suture morphology.
AB  - There is no consensus on when in the fish-tetrapod transition suction feeding,
      the primary method of prey capture in the aquatic realm, evolved into the direct
      biting on prey typical of terrestrial animals. Here, we show that differences in
      the morphology of selected cranial sutures between species that span the fish
      tetrapod transition (the Devonian osteolepiform fish Eusthenopteron, the aquatic
      Devonian tetrapod Acanthostega, and the Permian terrestrial tetrapod Phonerpeton)
      can be used to infer when terrestrial feeding first appeared. Our approach
      consists of defining a sutural morphospace, assigning functional fields to that
      morphospace based on our previous measurements of suture function made during
      feeding in the living fish Polypterus, inferring the functions of the fossil
      sutures based on where they fall in the morphospace, and then using the
      correlation between feeding mode and the patterns of inferred suture function
      across the skull roof in taxa where feeding mode is unambiguous to infer the
      feeding mode practiced by Acanthostega. Using this procedure, we find that the
      suture morphologies of Acanthostega are inconsistent with the hypothesis that it
      captured prey primarily by means of suction, which suggests that it may have
      bitten directly on prey at or near the water's edge. Thus, our data strongly
      support the hypothesis that the terrestrial mode of feeding first emerged in
      aquatic taxa.

PMID- 17438286
TI  - Stepwise formation of the bacterial flagellar system.
AB  - Elucidating the origins of complex biological structures has been one of the
      major challenges of evolutionary studies. The bacterial flagellum is a primary
      example of a complex apparatus whose origins and evolutionary history have proven
      difficult to reconstruct. The gene clusters encoding the components of the
      flagellum can include >50 genes, but these clusters vary greatly in their numbers
      and contents among bacterial phyla. To investigate how this diversity arose, we
      identified all homologs of all flagellar proteins encoded in the complete genome
      sequences of 41 flagellated species from 11 bacterial phyla. Based on the
      phylogenetic occurrence and histories of each of these proteins, we could
      distinguish an ancient core set of 24 structural genes that were present in the
      common ancestor to all Bacteria. Within a genome, many of these core genes show
      sequence similarity only to other flagellar core genes, indicating that they were
      derived from one another, and the relationships among these genes suggest the
      probable order in which the structural components of the bacterial flagellum
      arose. These results show that core components of the bacterial flagellum
      originated through the successive duplication and modification of a few, or
      perhaps even a single, precursor gene.

PMID- 17438287
TI  - Distinct contribution of electrostatics, initial conformational ensemble, and
      macromolecular stability in RNA folding.
AB  - We distinguish the contribution of the electrostatic environment, initial
      conformational ensemble, and macromolecular stability on the folding mechanism of
      a large RNA using a combination of time-resolved "Fast Fenton" hydroxyl radical
      footprinting and exhaustive kinetic modeling. This integrated approach allows us
      to define the folding landscape of the L-21 Tetrahymena thermophila group I
      intron structurally and kinetically from its earliest steps with unprecedented
      accuracy. Distinct parallel pathways leading the RNA to its native form upon its
      Mg(2+)-induced folding are observed. The structures of the intermediates
      populating the pathways are not affected by variation of the concentration and
      type of background monovalent ions (electrostatic environment) but are altered by
      a mutation that destabilizes one domain of the ribozyme. Experiments starting
      from different conformational ensembles but folding under identical conditions
      show that whereas the electrostatic environment modulates molecular flux through
      different pathways, the initial conformational ensemble determines the
      partitioning of the flux. This study showcases a robust approach for the
      development of kinetic models from collections of local structural probes.

PMID- 17438288
TI  - Recruitment of an inhibitory hippocampal network after bursting in a single
      granule cell.
AB  - The hippocampal CA3 area, an associational network implicated in memory function,
      receives monosynaptic excitatory as well as disynaptic inhibitory input through
      the mossy-fiber axons of the dentate granule cells. Synapses made by mossy fibers
      exhibit low release probability, resulting in high failure rates at resting
      discharge frequencies of 0.1 Hz. In recordings from functionally connected pairs
      of neurons, burst firing of a granule cell increased the probability of glutamate
      release onto both CA3 pyramidal cells and inhibitory interneurons, such that
      subsequent low-frequency stimulation evoked biphasic excitatory/inhibitory
      responses in a CA3 pyramidal cell, an effect lasting for minutes. Analysis of the
      unitary connections in the circuit revealed that granule cell bursting caused
      powerful activation of an inhibitory network, thereby transiently suppressing
      excitatory input to CA3 pyramidal cells. This phenomenon reflects the high
      incidence of spike-to-spike transmission at granule cell to interneuron synapses,
      the numerically much greater targeting by mossy fibers of inhibitory interneurons
      versus principal cells, and the extensively divergent output of interneurons
      targeting CA3 pyramidal cells. Thus, mossy-fiber input to CA3 pyramidal cells
      appears to function in three distinct modes: a resting mode, in which synaptic
      transmission is ineffectual because of high failure rates; a bursting mode, in
      which excitation predominates; and a postbursting mode, in which inhibitory input
      to the CA3 pyramidal cells is greatly enhanced. A mechanism allowing the
      transient recruitment of inhibitory input may be important for controlling
      network activity in the highly interconnected CA3 pyramidal cell region.

PMID- 17438289
TI  - Kruppel-like factor 15 is a regulator of cardiomyocyte hypertrophy.
AB  - Cardiac hypertrophy is a common response to injury and hemodynamic stress and an
      important harbinger of heart failure and death. Herein, we identify the Kruppel
      like factor 15 (KLF15) as an inhibitor of cardiac hypertrophy. Myocardial
      expression of KLF15 is reduced in rodent models of hypertrophy and in biopsy
      samples from patients with pressure-overload induced by chronic valvular aortic
      stenosis. Overexpression of KLF15 in neonatal rat ventricular cardiomyocytes
      inhibits cell size, protein synthesis and hypertrophic gene expression. KLF15
      null mice are viable but, in response to pressure overload, develop an eccentric
      form of cardiac hypertrophy characterized by increased heart weight, exaggerated
      expression of hypertrophic genes, left ventricular cavity dilatation with
      increased myocyte size, and reduced left ventricular systolic function.
      Mechanistically, a combination of promoter analyses and gel-shift studies suggest
      that KLF15 can inhibit GATA4 and myocyte enhancer factor 2 function. These
      studies identify KLF15 as part of a heretofore unrecognized pathway regulating
      the cardiac response to hemodynamic stress.

PMID- 17438290
TI  - Vitellogenin, juvenile hormone, insulin signaling, and queen honey bee longevity.
AB  - In most animals, longevity is achieved at the expense of fertility, but queen
      honey bees do not show this tradeoff. Queens are both long-lived and fertile,
      whereas workers, derived from the same genome, are both relatively short-lived
      and normally sterile. It has been suggested, on the basis of results from
      workers, that vitellogenin (Vg), best known as a yolk protein synthesized in the
      abdominal fat body, acts as an antioxidant to promote longevity in queen bees. We
      explored this hypothesis, as well as related roles of insulin-IGF-1 signaling and
      juvenile hormone. Vg was expressed in thorax and head fat body cells in an age
      dependent manner, with old queens showing much higher expression than workers. In
      contrast, Vg expression in worker head was much lower. Queens also were more
      resistant to oxidative stress than workers. These results support the hypothesis
      that caste-specific differences in Vg expression are involved in queen longevity.
      Consistent with predictions from Drosophila, old queens had lower head expression
      of insulin-like peptide and its putative receptors than did old workers. Juvenile
      hormone affected the expression of Vg and insulin-IGF-1 signaling genes in
      opposite directions. These results suggest that conserved and species-specific
      mechanisms interact to regulate queen bee longevity without sacrificing
      fecundity.

PMID- 17438291
TI  - The same genomic region conditions clonal deletion and clonal deviation to the
      CD8alphaalpha and regulatory T cell lineages in NOD versus C57BL/6 mice.
AB  - Clonal deviation is a mechanism by which immature thymocytes expressing a self
      reactive T cell antigen receptor (TCR) are rescued from clonal deletion by
      adopting an alternative differentiation pathway resistant to apoptosis. Here, we
      confirm and generalize previous indications that genetic alleles in NOD mice
      condition ineffective clonal deviation toward the CD8alphaalpha lineage, a
      peculiar population of TCRalphabeta lymphocytes that electively colonizes the
      intraepithelial lymphocyte pool in the gut. Thymic selection of CD8alphaalpha
      cells was very age-dependent, occurring almost exclusively in the postnatal
      period. Fewer CD8alphaalpha cells were found in the thymus and intraepithelial
      lymphocytes of BDC2.5 TCR transgenic mice on the NOD than on the C57BL/6 (B6)
      background; this paucity extended to standard NOD mice, albeit to a lesser
      extent. CD8alphaalpha cells resided in the BDC2.5 pancreatic infiltrate, and they
      were more abundant on the B6 than the NOD background, correlating with
      aggressivity of the lesion. A (B6(g7) x NOD)F(2) intercross in agonist-challenged
      BDC2.5 fetal thymic organ cultures demonstrated the existence of a major
      quantitative trait locus on chromosome 3, coincident with an interval associated
      with resistance to clonal deletion. A replicate linkage confirmed these positions
      and showed that the same region also controls clonal deviation toward the
      CD4(+)FoxP3(+) regulatory T cell lineage. That clonal deviation toward the
      CD8alphaalpha and regulatory T cell pathways share genetic control further
      highlights the similarities between these two "rescue lineages," consistent with
      an immunoregulatory role for CD8alphaalpha cells.

PMID- 17438292
TI  - Hairpin extensions enhance the efficacy of mycolyl transferase-specific antisense
      oligonucleotides targeting Mycobacterium tuberculosis.
AB  - We have investigated the efficacy of modifying gene-specific antisense
      phosphorothioate oligodeoxyribonucleotides (PS-ODNs) by the addition of 5' and 3'
      hairpin extensions. As a model system, we have targeted the Mycobacterium
      tuberculosis 30/32-kDa mycolyl transferase protein complex genes encoding three
      highly related enzymes (antigens 85 A, B, and C). Whereas the addition of a
      hairpin extension at only one end of the PS-ODNs did not improve their inhibitory
      capacity, the addition of hairpin extensions at both ends enhanced their capacity
      to inhibit M. tuberculosis multiplication in comparison with unmodified PS-ODNs.
      A combination of three 5'-, 3'-hairpin-modified PS-ODNs (HPS-ODNs) targeting each
      of the three mycolyl transferase transcripts inhibited bacterial growth in broth
      culture by approximately 1.75 log units (P < 0.0001) and in human THP-1
      macrophages by approximately 0.4 log units (P < 0.0001), which to our knowledge
      has not previously been demonstrated for any PS-ODN; reduced target gene
      transcription by > or =90%; caused approximately 90% reduction in mycolyl
      transferase expression; and increased bacterial sensitivity to isoniazid by 8
      fold. The growth-inhibitory effect of the HPS-ODNs was gene-specific. Mismatched
      HPS-ODNs had no growth-inhibitory capacity. This study demonstrates that 5'- and
      3'-HPS-ODNs are highly efficacious against M. tuberculosis and supports the
      further development of antisense technology as a therapeutic modality against
      tuberculosis.

PMID- 17438293
TI  - Connecting protein structure with predictions of regulatory sites.
AB  - A common task posed by microarray experiments is to infer the binding site
      preferences for a known transcription factor from a collection of genes that it
      regulates and to ascertain whether the factor acts alone or in a complex. The
      converse problem can also be posed: Given a collection of binding sites, can the
      regulatory factor or complex of factors be inferred? Both tasks are substantially
      facilitated by using relatively simple homology models for protein-DNA
      interactions, as well as the rapidly expanding protein structure database. For
      budding yeast, we are able to construct reliable structural models for 67
      transcription factors and with them redetermine factor binding sites by using a
      Bayesian Gibbs sampling algorithm and an extensive protein localization data set.
      For 49 factors in common with a prior analysis of this data set (based largely on
      phylogenetic conservation), we find that half of the previously predicted binding
      motifs are in need of some revision. We also solve the inverse problem of
      ascertaining the factors from the binding sites by assigning a correct protein
      fold to 25 of the 49 cases from a previous study. Our approach is easily extended
      to other organisms, including higher eukaryotes. Our study highlights the utility
      of enlarging current structural genomics projects that exhaustively sample fold
      structure space to include all factors with significantly different DNA-binding
      specificities.

PMID- 17438294
TI  - The zebrafish candyfloss mutant implicates extracellular matrix adhesion failure
      in laminin alpha2-deficient congenital muscular dystrophy.
AB  - Mutations in the human laminin alpha2 (LAMA2) gene result in the most common form
      of congenital muscular dystrophy (MDC1A). There are currently three models for
      the molecular basis of cellular pathology in MDC1A: (i) lack of LAMA2 leads to
      sarcolemmal weakness and failure, followed by cellular necrosis, as is the case
      in Duchenne muscular dystrophy (DMD); (ii) loss of LAMA2-mediated signaling
      during the development and maintenance of muscle tissue results in myoblast
      proliferation and fusion defects; (iii) loss of LAMA2 from the basement membrane
      of the Schwann cells surrounding the peripheral nerves results in a lack of motor
      stimulation, leading to effective denervation atrophy. Here we show that the
      degenerative muscle phenotype in the zebrafish dystrophic mutant, candyfloss
      (caf) results from mutations in the laminin alpha2 (lama2) gene. In vivo time
      lapse analysis of mechanically loaded fibers and membrane permeability assays
      suggest that, unlike DMD, fiber detachment is not initially associated with
      sarcolemmal rupture. Early muscle formation and myoblast fusion are normal,
      indicating that any deficiency in early Lama2 signaling does not lead to muscle
      pathology. In addition, innervation by the primary motor neurons is unaffected,
      and fiber detachment stems from muscle contraction, demonstrating that muscle
      atrophy through lack of motor neuron activity does not contribute to pathology in
      this system. Using these and other analyses, we present a model of lama2 function
      where fiber detachment external to the sarcolemma is mechanically induced, and
      retracted fibers with uncompromised membranes undergo subsequent apoptosis.

PMID- 17438295
TI  - Molecular basis of coiled-coil formation.
AB  - Coiled coils have attracted considerable interest as design templates in a wide
      range of applications. Successful coiled-coil design strategies therefore require
      a detailed understanding of coiled-coil folding. One common feature shared by
      coiled coils is the presence of a short autonomous helical folding unit, termed
      "trigger sequence," that is indispensable for folding. Detailed knowledge of
      trigger sequences at the molecular level is thus key to a general understanding
      of coiled-coil formation. Using a multidisciplinary approach, we identify and
      characterize here the molecular determinants that specify the helical
      conformation of the monomeric early folding intermediate of the GCN4 coiled coil.
      We demonstrate that a network of hydrogen-bonding and electrostatic interactions
      stabilize the trigger-sequence helix. This network is rearranged in the final
      dimeric coiled-coil structure, and its destabilization significantly slows down
      GCN4 leucine zipper folding. Our findings provide a general explanation for the
      molecular mechanism of coiled-coil formation.

PMID- 17438296
TI  - Disruption of innate immunity due to mitochondrial targeting of a picornaviral
      protease precursor.
AB  - Mitochondrial antiviral signaling protein (MAVS) is an essential component of
      virus-activated signaling pathways that induce protective IFN responses. Its
      localization to the outer mitochondrial membrane suggests an important yet
      unexplained role for mitochondria in innate immunity. Here, we show that
      hepatitis A virus (HAV), a hepatotropic picornavirus, ablates type 1 IFN
      responses by targeting the 3ABC precursor of its 3C(pro) cysteine protease to
      mitochondria where it colocalizes with and cleaves MAVS, thereby disrupting
      activation of IRF3 through the MDA5 pathway. The 3ABC cleavage of MAVS requires
      both the protease activity of 3C(pro) and a transmembrane domain in 3A that
      directs 3ABC to mitochondria. Lacking this domain, mature 3C(pro) protease is
      incapable of MAVS proteolysis. HAV thus disrupts host signaling by a mechanism
      that parallels that of the serine NS3/4A protease of hepatitis C virus, but
      differs in its use of a stable, catalytically active polyprotein processing
      intermediate. The unique requirement for mitochondrial localization of 3ABC
      underscores the importance of mitochondria to host control of virus infections
      within the liver.

PMID- 17438297
TI  - Specificity of the medaka enteropeptidase serine protease and its usefulness as a
      biotechnological tool for fusion-protein cleavage.
AB  - We cloned two distinct cDNAs for enteropeptidase (EP) from the intestine of the
      medaka, Oryzias latipes, which is a small freshwater teleost. The mRNAs code for
      EP-1 (1,036 residues) and EP-2 (1,043 residues), both of which have a unique,
      conserved domain structure of the N-terminal heavy chain and C-terminal catalytic
      serine protease light chain. When compared with mammalian EP serine proteases,
      the medaka enzyme exhibited extremely low amidolytic activity for small synthetic
      peptide substrates. Twelve mutated forms of the medaka EP protease were produced
      by site-directed mutagenesis. Among them, one mutant protease, E173A, was found
      to have considerably reduced nonspecific hydrolytic activities both for synthetic
      and protein substrates without serious reduction of its Asp-Asp-Asp-Asp-Lys
      (D(4)K)-cleavage activity. For the cleavage of fusion proteins containing a D(4)K
      cleavage site, the medaka EP proteases were shown to have advantages over their
      mammalian counterparts. Based on our present data, we propose that the E173A
      mutant is the most appropriate protease to specifically cleave proteins
      containing the D(4)K cleavage sequence.

PMID- 17438298
TI  - Growth, innovation, scaling, and the pace of life in cities.
AB  - Humanity has just crossed a major landmark in its history with the majority of
      people now living in cities. Cities have long been known to be society's
      predominant engine of innovation and wealth creation, yet they are also its main
      source of crime, pollution, and disease. The inexorable trend toward urbanization
      worldwide presents an urgent challenge for developing a predictive, quantitative
      theory of urban organization and sustainable development. Here we present
      empirical evidence indicating that the processes relating urbanization to
      economic development and knowledge creation are very general, being shared by all
      cities belonging to the same urban system and sustained across different nations
      and times. Many diverse properties of cities from patent production and personal
      income to electrical cable length are shown to be power law functions of
      population size with scaling exponents, beta, that fall into distinct
      universality classes. Quantities reflecting wealth creation and innovation have
      beta approximately 1.2 >1 (increasing returns), whereas those accounting for
      infrastructure display beta approximately 0.8 <1 (economies of scale). We predict
      that the pace of social life in the city increases with population size, in
      quantitative agreement with data, and we discuss how cities are similar to, and
      differ from, biological organisms, for which beta<1. Finally, we explore possible
      consequences of these scaling relations by deriving growth equations, which
      quantify the dramatic difference between growth fueled by innovation versus that
      driven by economies of scale. This difference suggests that, as population grows,
      major innovation cycles must be generated at a continually accelerating rate to
      sustain growth and avoid stagnation or collapse.

PMID- 17438299
TI  - Structures and spectral signatures of protonated water networks in
      bacteriorhodopsin.
AB  - Networks of internal water molecules are thought to provide proton transfer
      pathways in many enzymatic and photosynthetic reactions. Extremely broad
      absorption continua observed in recent IR spectroscopic measurements on the
      photodriven proton pump bacteriorhodopsin (BR) suggest such networks may also
      serve as proton storage and release sites for these reactions. By combining
      electronic structure calculations with molecular mechanical force fields, we
      examine the dynamics and the resulting IR spectra of two protonated water
      networks, H+.(H2O)3 and H+.(H2O)4, in the release pocket of the initial state of
      BR, which possibly serve as proton donors to the extracellular surface. For both
      network sizes, topologically similar structures are found, which are anchored at
      residues E194 and E204 and stabilized by additional hydrogen bonds from
      neighboring protein side chains. These protonated water networks assume neither
      the classic Zundel nor Eigen motives but prefer wire-like topologies. Upon
      gauging calculated IR spectra of finite clusters with experimental gas-phase
      data, it is possible to link spectral features computed for these chain-like
      structures in the initial state of the BR photocycle to the measured absorption
      continua, in particular for the larger H+.(H2O)4 network. Furthermore, the free
      energy of proton dislocation along these chains is found to be within the range
      that is easily accessible at room temperature because of fluctuations.

PMID- 17438300
TI  - Real-time control of the energy landscape by force directs the folding of RNA
      molecules.
AB  - The rugged folding-energy landscapes of RNAs often display many competing minima.
      How do RNAs discriminate among competing conformations in their search for the
      native state? By using optical tweezers, we show that the folding-energy
      landscape can be manipulated to control the fate of an RNA: individual RNA
      molecules can be induced into either native or misfolding pathways by modulating
      the relaxation rate of applied force and even be redirected during the folding
      process to switch from misfolding to native folding pathways. Controlling folding
      pathways at the single-molecule level provides a way to survey the manifold of
      folding trajectories and intermediates, a capability that previously was
      available only to theoretical studies.

PMID- 17438301
TI  - Out-of-office blood pressure control among treated subjects.

PMID- 17438303
TI  - Sympathetic activity, heart failure, obesity, and metabolic syndrome: is there
      any role for obstructive sleep apnea?

PMID- 17438305
TI  - Prolonged activation of the baroreflex abolishes obesity-induced hypertension.
AB  - Prolonged electrical activation of the carotid baroreflex produces sustained
      reductions in sympathetic activity and arterial pressure in normotensive dogs.
      The main goal of this study was to assess the influence of prolonged baroreflex
      activation on arterial pressure and neurohormonal responses in 6 dogs with
      obesity-induced hypertension. After control measurements, the diet was
      supplemented with cooked beef fat for 6 weeks, whereas sodium intake was held
      constant. After 4 weeks of the high-fat diet, there were increments in body
      weight from 25.8+/-0.7 to 38.6+/-1.0 kg, mean arterial pressure from 97+/-2 to
      110+/-3 mm Hg, heart rate from 67+/-3 to 91+/-4 bpm, and plasma norepinephrine
      concentration from 141+/-35 to 280+/-52 pg/mL. Plasma glucose and insulin
      concentrations were elevated, but increases in plasma renin activity during the
      initial weeks of the high-fat diet were not sustained. During week 5, baroreflex
      activation resulted in sustained reductions in mean arterial pressure, heart
      rate, and plasma norepinephrine concentration; at the end of week 5, these values
      were 87+/-2 mm Hg, 77+/-4 bpm, and 166+/-45 pg/mL, respectively. These suppressed
      values returned to week 4 levels during a 7-day recovery period after baroreflex
      activation. There were no changes in plasma glucose or insulin concentrations, or
      plasma renin activity during prolonged baroreflex activation. These findings
      indicate that baroreflex activation can chronically suppress the
      sympathoexcitation associated with obesity and abolish the attendant hypertension
      while having no effect on hyperinsulinemia or hyperglycemia.

PMID- 17438304
TI  - Norepinephrine, via beta-adrenoceptors, regulates bumetanide-sensitive
      cotransporter type 1 expression in thick ascending limb cells.
AB  - The sympathetic nervous system, via norepinephrine, regulates renal sodium
      transport, and chronic sympathetic activation causes sustained increases in blood
      pressure by reducing sodium excretion. Our previous studies show that chronic
      norepinephrine infusion increases the abundance of the bumetanide-sensitive
      cotransporter type 1, the apical sodium transporter of the thick ascending limb
      of Henle's loop. The present study was initiated to elucidate the mechanisms by
      which norepinephrine regulates the protein levels of this transporter in an
      immortalized thick ascending limb epithelial cell line. Treatment with
      norepinephrine, either alone or in the presence of actinomycin D or
      cycloheximide, had no effect on cotransporter mRNA levels. Treatment with
      norepinephrine, however, increased bumetanide-sensitive cotransporter type 1
      protein levels (70% increase versus control; P=0.012), and pretreatment with
      cycloheximide blocked the effect of norepinephrine on bumetanide-sensitive
      cotransporter type 1 protein levels. To further elucidate the mechanism, thick
      ascending limb cells were treated with norepinephrine in the presence of
      phentolamine (alpha-adrenoceptor blocker), propranolol (beta-adrenoceptor
      blocker), SQ22536 (adenylyl cyclase inhibitor), PD098059 (mitogen-activated
      protein kinase pathway inhibitor), H-89 (protein kinase A inhibitor), or
      staurosporine (protein kinase C inhibitor). Treatment with propranolol, SQ22536,
      and H-89 abolished the effects of norepinephrine on bumetanide-sensitive
      cotransporter type 1 protein levels, whereas staurosporine had no effect.
      Treatment with PD098059 partially inhibited the effects of norepinephrine (40%
      decrease versus norepinephrine; P=0.03), and treatment with phentolamine
      potentiated the effects of norepinephrine (30% increase versus norepinephrine;
      P=0.02) on bumetanide-sensitive cotransporter type 1 protein levels. We conclude
      that regulation of bumetanide-sensitive cotransporter type 1 by norepinephrine
      proceeds via the beta-adrenoceptor receptor-cAMP-protein kinase A pathway that
      involves in part mitogen-activated protein kinases and that alpha-adrenoceptor
      activation negatively regulates bumetanide-sensitive cotransporter type 1 protein
      levels.

PMID- 17438306
TI  - Uninephrectomy in young age or chronic salt loading causes salt-sensitive
      hypertension in adult rats.
AB  - The importance of nephron endowment and salt intake for the development of
      hypertension is under debate. The present study was designed to investigate
      whether reduced nephron number, after completion of nephrogenesis, or chronic
      salt loading causes renal injury and salt-sensitive hypertension in adulthood.
      Rats were operated at 3 weeks of age (after completed nephrogenesis) and then
      subjected to either normal or high-salt diets for 6 to 8 weeks. Four different
      experimental groups were used: sham-operated animals raised with normal-salt diet
      (controls) or high-salt diet (HS) and uninephrectomized animals raised with
      normal-salt diet (UNX) or high-salt diet (UNX+HS). In the adult animals, renal
      and cardiovascular functions were evaluated and blood pressure recorded
      telemetrically under different sodium conditions (normal, high, and low).
      Hypertension was present in UNX+HS (122+/-9 mm Hg), UNX (101+/-3 mm Hg), and HS
      (96+/-1 mm Hg) groups on normal-salt diets compared with the controls (84+/-2 mm
      Hg), and the blood pressure was salt sensitive (high- versus normal-salt diet;
      23+/-3, 9+/-2, 7+/-2, and 1+/-1 mm Hg, respectively). The hypertensive groups
      (UNX+HS, UNX, and HS) had increased diuresis and reduced ability to concentrate
      urine. The glomerular filtration rate (milliliters per minute) in anesthetized
      rats was reduced in the UNX+HS (2.36+/-0.30) and UNX animals (2.00+/-0.31)
      compared with both HS animals (3.55+/-0.45) and controls (3.01+/-0.35).
      Hypertensive groups displayed reduced plasma renin concentrations during high
      sodium conditions and hypertrophic kidneys and hearts with various degrees of
      histopathologic changes. In conclusion, at a young age after completed
      nephrogenesis, uninephrectomy or chronic salt loading causes renal and
      cardiovascular injury with salt-sensitive hypertension.

PMID- 17438307
TI  - Exercise training restores baroreflex sensitivity in never-treated hypertensive
      patients.
AB  - The effects of exercise training on baroreflex control of sympathetic nerve
      activity in human hypertension are unknown. We hypothesized that exercise
      training would improve baroreflex control of muscle sympathetic nerve activity
      (MSNA) and heart rate (HR) in patients with hypertension and that exercise
      training would reduce MSNA and blood pressure (BP) in hypertensive patients.
      Twenty never-treated hypertensive patients were randomly divided into 2 groups:
      exercise-trained (n=11; age: 46+/-2 years) and untrained (n=9; age: 42+/-2 years)
      patients. An age-matched normotensive exercise-trained group (n=12; age: 42+/-2
      years) was also studied. Baroreflex control of MSNA (microneurography) and HR
      (ECG) was assessed by stepwise intravenous infusions of phenylephrine and sodium
      nitroprusside and analyzed by linear regression. BP was monitored on a beat-to
      beat basis. Exercise training consisted of three 60-minute exercise sessions per
      week for 4 months. Under baseline conditions (before training), BP and MSNA were
      similar between hypertensive groups but significantly increased when compared
      with the normotensive group. Baroreflex control of MSNA and HR was similar
      between hypertensive groups but significantly decreased when compared with the
      normotensive group. In hypertensive patients, exercise training significantly
      reduced BP (P<0.01) and MSNA (P<0.01) levels and significantly increased
      baroreflex control of MSNA and HR during increases (P<0.01 and P<0.03,
      respectively) and decreases (P<0.01 and P<0.03, respectively) in BP. The baseline
      (preintervention) difference in baroreflex sensitivity between hypertensive
      patients and normotensive individuals was no longer observed after exercise
      training. No significant changes were found in untrained hypertensive patients.
      In conclusion, exercise training restores the baroreflex control of MSNA and HR
      in hypertensive patients. In addition, exercise training normalizes MSNA and
      decreases BP levels in these patients.

PMID- 17438309
TI  - Quality improvement and ethical oversight.

PMID- 17438308
TI  - Alteration of volume-regulated chloride movement in rat cerebrovascular smooth
      muscle cells during hypertension.
AB  - The cerebrovascular remodeling is a prominent feature of hypertension and
      considered a major risk factor for stroke. Cerebrovascular smooth muscle cells
      meet volume challenge during this pathophysiological process. Our previous
      studies suggest that volume regulated chloride channels may be critical to the
      cell cycle of vascular smooth muscle cells. However, it is unknown whether the
      volume-regulated chloride movement is altered in hypertension. Therefore, we
      directly measured the concentration of intracellular chloride ([Cl(-)](i)) in rat
      basilar arterial smooth muscle cells isolated from control rats and rats that
      were made hypertensive for 1 to 12 weeks after partial renal artery constriction
      (2-kidney, 2-clip method) using a 6-methoxy-N-ethylquinolinium iodide
      fluorescence probe. The [Cl(-)](i) in isotonic solution showed no difference in
      all of the groups. After hypotonic perfusion, the reduction in [Cl(-)](i) was
      more prominent in hypertensive cerebrovascular smooth muscle cells than in sham
      control cells. Genistein, a protein tyrosine kinase inhibitor, inhibited
      hypotonic-induced reduction in [Cl(-)](i), whereas sodium orthovanadate, a
      protein-tyrosine phosphatase inhibitor, enhanced hypotonic-induced reduction in
      [Cl(-)](i) in both groups. The percentage inhibition of reduction in [Cl(-)](i)
      by genistein on volume-regulated chloride movement has a positive correlation
      with blood pressure levels in the 2-kidney, 2-clip hypertensive group, as is the
      case for the percentage increase of reduction in [Cl(-)](i) by sodium
      orthovanadate. Antihypertensive therapy with the angiotensin-converting enzyme
      inhibitor captopril completely reversed abnormal volume-regulated chloride
      movement in hypertensive rats. We conclude that volume-regulated chloride
      movement is augmented in rat cerebrovascular smooth muscle cells in proportion to
      the severity of hypertension.

PMID- 17438311
TI  - Summaries for patients. Sequential therapy versus standard triple-drug therapy
      for Helicobacter pylori eradication.

PMID- 17438310
TI  - The ethics of using quality improvement methods in health care.
AB  - Quality improvement (QI) activities can improve health care but must be conducted
      ethically. The Hastings Center convened leaders and scholars to address ethical
      requirements for QI and their relationship to regulations protecting human
      subjects of research. The group defined QI as systematic, data-guided activities
      designed to bring about immediate improvements in health care delivery in
      particular settings and concluded that QI is an intrinsic part of normal health
      care operations. Both clinicians and patients have an ethical responsibility to
      participate in QI, provided that it complies with specified ethical requirements.
      Most QI activities are not human subjects research and should not undergo review
      by an institutional review board; rather, appropriately calibrated supervision of
      QI activities should be part of professional supervision of clinical practice.
      The group formulated a framework that would use key characteristics of a project
      and its context to categorize it as QI, human subjects research, or both, with
      the potential of a customized institutional review board process for the overlap
      category. The group recommended a period of innovation and evaluation to refine
      the framework for ethical conduct of QI and to integrate that framework into
      clinical practice.

PMID- 17438312
TI  - Summaries for patients. Adherence to nonnucleoside reverse transcriptase
      inhibitor-based HIV therapy and patient outcomes.

PMID- 17438313
TI  - Summaries for patients. Successful treatment of aminoglycoside-resistant
      endocarditis with ampicillin and ceftriaxone.

PMID- 17438314
TI  - Sequential therapy versus standard triple-drug therapy for Helicobacter pylori
      eradication: a randomized trial.
AB  - BACKGROUND: Antimicrobial resistance has decreased eradication rates for
      Helicobacter pylori infection worldwide. OBJECTIVE: To determine whether
      sequential treatment eradicates H. pylori infection better than standard triple
      drug therapy for adults with dyspepsia or peptic ulcers. DESIGN: Randomized,
      double-blind, placebo-controlled trial. SETTING: Two Italian hospitals between
      September 2003 and April 2006. PATIENTS: 300 patients with dyspepsia or peptic
      ulcers. MEASUREMENTS: (13)C-urea breath test, upper endoscopy, histologic
      evaluation, rapid urease test, bacterial culture, and assessment of antibiotic
      resistance. INTERVENTION: A 10-day sequential regimen (40 mg of pantoprazole, 1 g
      of amoxicillin, and placebo, each administered twice daily for the first 5 days,
      followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of
      tinidazole, each administered twice daily for the remaining 5 days) or standard
      10-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of
      amoxicillin, each administered twice daily). RESULTS: The eradication rate
      achieved with the sequential regimen was significantly greater than that obtained
      with the standard treatment in the intention-to-treat analysis (89% vs. 77%; P =
      0.0134; difference, 12% [95% CI, 3% to 20%]), the modified intention-to-treat
      analysis (91% vs. 78%; P = 0.0022; difference, 13% [CI, 5% to 21%]), and the per
      protocol analysis (93% vs. 79%; P = 0.0013; difference, 14% [CI, 6% to 21%]).
      Sequential therapy was significantly more effective in patients with
      clarithromycin-resistant strains (89% vs. 29%; P = 0.0034). The incidence of
      major and minor side effects did not differ between therapy groups (17% in both
      groups). One patient (0.7%) in the standard therapy group discontinued treatment
      because of side effects. LIMITATIONS: Follow-up was incomplete in 4.6% and 2.7%
      patients in the sequential therapy and standard therapy groups, respectively. The
      results may not be generalizable to other countries. Sequential therapy may be
      more effective because it includes 1 additional antibiotic (tinidazole) that is
      not contained in standard therapy. CONCLUSIONS: Sequential therapy is
      statistically significant compared with standard therapy for eradicating H.
      pylori infection and is statistically significantly more effective in patients
      with clarithromycin-resistant strains. Side effects are similar with both
      treatment regimens and are rarely severe enough to cause discontinuation of
      therapy. ClinicalTrials.gov registration number: NCT00403364.

PMID- 17438315
TI  - Adherence to nonnucleoside reverse transcriptase inhibitor-based HIV therapy and
      virologic outcomes.
AB  - BACKGROUND: Adherence of 95% or more to unboosted protease regimens is required
      for optimal virologic suppression in HIV-1-infected patients. Whether the same is
      true for nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy is
      unclear. OBJECTIVE: To assess the relationship between adherence to NNRTI-based
      therapy and viral load in treatment-naive patients. DESIGN: Observational cohort
      study. SETTING: Private-sector HIV and AIDS disease management program in South
      Africa. PATIENTS: 2821 adults infected with HIV who began NNRTI-based therapy
      between January 1998 and March 2003 (2764 patients [98%] were enrolled after
      December 2000). MEASUREMENTS: Adherence was assessed by monthly pharmacy claims.
      The primary end point was sustained viral load suppression (<400 copies/mL) in
      100% of recorded viral load measurements throughout follow-up. Secondary end
      points included time to initial viral load suppression and time to subsequent
      virologic failure (>400 copies/mL). RESULTS: The median follow-up period was 2.2
      years (interquartile range, 1.7 to 2.7 years). The proportion of patients with
      sustained viral load suppression ranged from 13% (41 of 325 patients) in patients
      who filled less than 50% of antiretroviral drug prescriptions to 73% (725 of 997
      patients) in those who filled 100% of antiretroviral drug prescriptions. Each 10%
      increase in pharmacy claim adherence greater than 50% was associated with a mean
      absolute increase of 0.10 in the proportion of patients with sustained virologic
      suppression (P < 0.001). Predictors for shorter time to virologic failure after
      initial suppression in multivariable Cox regression included CD4+ T-cell counts
      of 0.50 x 10(9) cells/L or less (hazard ratio, 1.60 [95% CI, 1.22 to 2.10] vs.
      CD4+ T-cell counts >0.20 x 10(9) cells/L), baseline viral load greater than 10(5)
      copies/mL (hazard ratio, 1.39 [CI, 1.14 to 1.70]), nevirapine-based regimen
      (hazard ratio, 1.43 [CI, 1.16 to 1.75]), and low pharmacy claim adherence (hazard
      ratio, 1.58 [CI, 1.48 to 1.69], per 10% decrease in adherence to 50%).
      LIMITATIONS: Observational study with adherence stratification at study end and
      lack of standardized timing for outcome measurement. CONCLUSION: Virologic
      outcomes improve in a linear dose-response manner as adherence to NNRTI-based
      regimens increases beyond 50%.

PMID- 17438316
TI  - Brief communication: treatment of Enterococcus faecalis endocarditis with
      ampicillin plus ceftriaxone.
AB  - BACKGROUND: High-level aminoglycoside resistance (HLAR) that precludes
      bactericidal synergism with penicillins or glycopeptides and nephrotoxicity
      related to aminoglycoside treatment are major problems in treating Enterococcus
      faecalis endocarditis. OBJECTIVE: To evaluate the efficacy and safety of
      ampicillin plus ceftriaxone for treating endocarditis due to E. faecalis with and
      without HLAR. DESIGN: Observational, open-label, nonrandomized, multicenter
      clinical trial. SETTING: 13 centers in Spain. PATIENTS: 21 patients with HLAR E.
      faecalis endocarditis and 22 patients with non-HLAR E. faecalis endocarditis. All
      were at risk for nephrotoxicity related to aminoglycoside use. INTERVENTION: 6
      week course of intravenous ampicillin, 2 g every 4 hours, plus intravenous
      ceftriaxone, 2 g every 12 hours. MEASUREMENTS: Clinical and microbiological
      outcomes. RESULTS: The clinical cure rate at 3 months was 67.4% (29 of 43
      patients) among all episodes. During treatment, 28.6% of patients with HLAR E.
      faecalis endocarditis and 18.2% of patients with non-HLAR E. faecalis
      endocarditis died of infection-related causes. The rate of clinical and
      microbiological cure in patients who completed the protocol was 100% in the HLAR
      E. faecalis endocarditis group. No episodes of breakthrough bacteremia occurred,
      although there were 2 relapses in the non-HLAR E. faecalis endocarditis group.
      Treatment was withdrawn in 1 case because of fever and skin rash. LIMITATIONS:
      The study had a small sample and was observational. CONCLUSION: The combination
      of ampicillin and ceftriaxone is effective and safe for treating HLAR E. faecalis
      endocarditis and could be a reasonable alternative for patients with non-HLAR E.
      faecalis endocarditis who are at increased risk for nephrotoxicity.

PMID- 17438317
TI  - Meta-analysis: chondroitin for osteoarthritis of the knee or hip.
AB  - BACKGROUND: Previous meta-analyses described moderate to large benefits of
      chondroitin in patients with osteoarthritis. However, recent large-scale trials
      did not find evidence of an effect. PURPOSE: To determine the effects of
      chondroitin on pain in patients with osteoarthritis. DATA SOURCES: The authors
      searched the Cochrane Central Register of Controlled Trials (1970 to 2006),
      MEDLINE (1966 to 2006), EMBASE (1980 to 2006), CINAHL (1970 to 2006), and
      conference proceedings; checked reference lists; and contacted authors. The last
      update of searches was performed on 30 November 2006. STUDY SELECTION: Studies
      were included if they were randomized or quasi-randomized, controlled trials that
      compared chondroitin with placebo or with no treatment in patients with
      osteoarthritis of the knee or hip. There were no language restrictions. DATA
      EXTRACTION: The authors extracted data in duplicate. Effect sizes were calculated
      from the differences in means of pain-related outcomes between treatment and
      control groups at the end of the trial, divided by the pooled SD. Trials were
      combined by using random-effects meta-analysis. DATA SYNTHESIS: 20 trials (3846
      patients) contributed to the meta-analysis, which revealed a high degree of
      heterogeneity among the trials (I2 = 92%). Small trials, trials with unclear
      concealment of allocation, and trials that were not analyzed according to the
      intention-to-treat principle showed larger effects in favor of chondroitin than
      did the remaining trials. When the authors restricted the analysis to the 3
      trials with large sample sizes and an intention-to-treat analysis, 40% of
      patients were included. This resulted in an effect size of -0.03 (95% CI, -0.13
      to 0.07; I2 = 0%) and corresponded to a difference of 0.6 mm on a 10-cm visual
      analogue scale. A meta-analysis of 12 trials showed a pooled relative risk of
      0.99 (CI, 0.76 to 1.31) for any adverse event. LIMITATIONS: For 9 trials, the
      authors had to use approximations to calculate effect sizes. Trial quality was
      generally low, heterogeneity among the trials made initial interpretation of
      results difficult, and exploring sources of heterogeneity in meta-regression and
      stratified analyses may be unreliable. CONCLUSIONS: Large-scale, methodologically
      sound trials indicate that the symptomatic benefit of chondroitin is minimal or
      nonexistent. Use of chondroitin in routine clinical practice should therefore be
      discouraged.

PMID- 17438318
TI  - Narrative review: antiretroviral therapy to prevent the sexual transmission of
      HIV-1.
AB  - Antiretroviral therapy (ART) has prolonged and improved the lives of persons
      infected with HIV. Theoretically, it can also be used to prevent the transmission
      of HIV. The pharmacology of ART in the male and female genital tract can be
      expected to affect the success of the intervention, and ART agents differ
      considerably in their ability to concentrate in genital tract secretions.
      Emergency ART is considered to be the standard of care after occupational
      exposures to fluids or tissues infected with HIV. More recently, ART for
      prophylaxis after nonoccupational HIV exposures has been widely used and most
      countries have developed specific guidelines for its implementation. However,
      developing clinical trials to prove the efficacy of ART postexposure prophylaxis
      has not been possible. Experiments with rhesus macaques suggest that therapy must
      be offered as soon as possible after exposure (within 72 hours) and must be
      continued for 28 days. Additional nonhuman primate experiments have demonstrated
      protection from HIV infection with ART preexposure prophylaxis, and several
      clinical trials are under way to evaluate the safety and efficacy of this
      approach. The degree to which ART offered to infected persons reduces
      infectiousness is of considerable public health importance, but the question has
      not been sufficiently answered. This article provides a review of the data on the
      use of ART to prevent the sexual transmission of HIV and identify challenges to
      improving and clarifying this approach.

PMID- 17438319
TI  - Linking cost sharing to value: an unrivaled yet unrealized public health
      opportunity.
AB  - As the financial burden of cost sharing continues to rise, patients increasingly
      avoid necessary care, thereby contributing to the high morbidity and mortality of
      the U.S. population compared with that of other developed countries. The
      rationale for cost sharing is often based on the moral hazard argument, which
      states that individuals may overuse care if they do not share in its costs. We
      evaluate this argument in detail, using it to distinguish between appropriate and
      inappropriate settings for cost sharing. Cost sharing may be appropriate when
      health services are of low value (low ratio of benefits to costs), whereas it is
      inappropriate when health services are of high value (high ratio of benefits to
      costs). In practice, cost sharing is rarely linked to value, and therefore much
      of the cost sharing that currently occurs is inappropriate and harmful. Cost
      effectiveness analysis is an objective method to estimate the value of health
      services and may be a way to systematically evaluate whether cost-sharing
      policies are appropriate. Systematic efforts to discourage inappropriate cost
      sharing may improve public health.

PMID- 17438320
TI  - Optimal treatment of chronic obstructive pulmonary disease: the search for the
      magic combination of inhaled bronchodilators and corticosteroids.

PMID- 17438321
TI  - Hungering for HAART.

PMID- 17438322
TI  - Chondroitin for pain in osteoarthritis.

PMID- 17438323
TI  - Reducing the incidence of high-altitude pulmonary edema.

PMID- 17438324
TI  - Reducing the incidence of high-altitude pulmonary edema.

PMID- 17438325
TI  - Lack of evidence for recommended low-density lipoprotein cholesterol treatment
      targets.

PMID- 17438326
TI  - Lack of evidence for recommended low-density lipoprotein cholesterol treatment
      targets.

PMID- 17438327
TI  - The perils of PERRLA.

PMID- 17438328
TI  - First-line therapy for hypertension.

PMID- 17438329
TI  - Posttraumatic stress disorder needs to be recognized in primary care.

PMID- 17438330
TI  - Critical role for transcription coactivator peroxisome proliferator-activated
      receptor (PPAR)-binding protein/TRAP220 in liver regeneration and PPARalpha
      ligand-induced liver tumor development.
AB  - Disruption of the gene encoding for the transcription coactivator peroxisome
      proliferator-activated receptor (PPAR)-binding protein (PBP/TRAP220/DRIP205/Med1)
      in the mouse results in embryonic lethality. Here, we have reported that targeted
      disruption of the Pbp/Pparbp gene in hepatocytes (Pbp(DeltaLiv)) impairs liver
      regeneration with low survival after partial hepatectomy. Analysis of cell cycle
      progression suggests a defective exit from quiescence, reduced BrdUrd
      incorporation, and diminished entry into G(2)/M phase in Pbp(DeltaLiv)
      hepatocytes after partial hepatectomy. Pbp(DeltaLiv) hepatocytes failed to
      respond to hepatocyte growth factor/scatter factor, implying that hepatic PBP
      deficiency affects c-met signaling. Pbp gene disruption also abolishes primary
      mitogen-induced liver cell proliferative response. Striking abrogation of CCl(4)
      induced hepatocellular proliferation and hepatotoxicity occurred in Pbp(DeltaLiv)
      mice pretreated with phenobarbital due to lack of expression of xenobiotic
      metabolizing enzymes necessary for CCl(4) activation. Pbp(DeltaLiv) mice,
      chronically exposed to Wy-14,643, a PPARalpha ligand, revealed a striking
      proliferative response and clonal expansion of a few Pbp(fl/fl) hepatocytes that
      escaped Cre-mediated gene deletion in Pbp(DeltaLiv) livers, but no proliferative
      expansion of PBP null hepatocytes was observed. In these Pbp(DeltaLiv) mice, none
      of the Wy-14,643-induced hepatic adenomas and hepatocellular carcinomas was
      derived from PBP(DeltaLiv) hepatocytes; all liver tumors developing in
      Pbp(DeltaLiv) mice maintained non-recombinant Pbp alleles and retained PBP
      expression. These studies provide direct evidence in support of a critical role
      of PBP/TRAP220 in liver regeneration, induction of hepatotoxicity, and
      hepatocarcinogenesis.

PMID- 17438331
TI  - Functional analysis of activating receptor LMIR4 as a counterpart of inhibitory
      receptor LMIR3.
AB  - The leukocyte mono-Ig-like receptor (LMIR) belongs to a new family of paired
      immunoreceptors. In this study, we analyzed activating receptor LMIR4/CLM-5 as a
      counterpart of inhibitory receptor LMIR3/CLM-1. LMIR4 is expressed in myeloid
      cells, including granulocytes, macrophages, and mast cells, whereas LMIR3 is more
      broadly expressed. The association of LMIR4 with Fc receptor-gamma among
      immunoreceptor tyrosine-based activation motif-bearing molecules was
      indispensable for LMIR4-mediated functions of bone marrow-derived mast cells, but
      dispensable for its surface expression. Cross-linking of LMIR4 led to Lyn- and
      Syk-dependent activation of bone marrow-derived mast cells, resulting in cytokine
      production and degranulation, whereas that of LMIR3 did not. The triggering of
      LMIR4 and TLR4 synergistically caused robust cytokine production in accordance
      with enhanced activation of ERK, whereas the co-ligation of LMIR4 and LMIR3
      dramatically abrogated cytokine production. Notably, intraperitoneal
      administration of lipopolysaccharide strikingly up-regulated LMIR3 and down
      regulated LMIR4, whereas that of granulocyte colony-stimulating factor up
      regulated both LMIR3 and LMIR4 in granulocytes. Cross-linking of LMIR4 in bone
      marrow granulocytes also resulted in their activation, which was enhanced by
      lipopolysaccharide. Collectively, these results suggest that the innate immune
      system is at least in part regulated by the qualitative and quantitative balance
      of the paired receptors LMIR3 and LMIR4.

PMID- 17438332
TI  - Resolution of the nuclear localization mechanism of glycogen synthase kinase-3:
      functional effects in apoptosis.
AB  - Mechanisms regulating the nuclear localization of glycogen synthase kinase-3beta
      (GSK3beta) remained enigmatic despite the crucial regulation by nuclear GSK3beta
      of important cellular functions. These include regulation of gene expression,
      cell cycle progression, and apoptosis, achieved by the phosphorylation by GSK3 of
      nuclear substrates (e.g. numerous transcription factors). We resolved this
      mechanism by identifying a bipartite nuclear localization sequence (NLS) that is
      necessary for the nuclear accumulation of GSK3beta and is sufficient to drive
      yellow fluorescent protein into the nucleus. Despite the NLS, most GSK3beta is
      cytosolic, sequestered in protein complexes that, although still mobile in the
      cytosol, block the NLS. Conditions promoting nuclear translocation of GSK3beta
      release it from cytosolic complexes, allowing the NLS to direct nuclear import.
      Using this information to prepare a nucleus-excluded active GSK3 construct, we
      found that the antiapoptotic effect of GSK3beta in tumor necrosis factor-induced
      apoptosis is mediated by cytosolic, not nuclear, GSK3beta. Identification of a
      GSK3beta NLS allows new strategies to decipher and manipulate its subcellular
      actions regulating gene expression and apoptosis and its involvement in diseases.

PMID- 17438333
TI  - Regulation of snf1 protein kinase in response to environmental stress.
AB  - The Saccharomyces cerevisiae Snf1 protein kinase, a member of the Snf1/AMPK (AMP
      activated protein kinase) family, has important roles in metabolic control,
      particularly in response to nutrient stress. Here we have addressed the role of
      Snf1 in responses to other environmental stresses. Exposure of cells to sodium
      ion stress, alkaline pH, or oxidative stress caused an increase in Snf1 catalytic
      activity and phosphorylation of Thr-210 in the activation loop, whereas treatment
      with sorbitol or heat shock did not. Inhibition of respiratory metabolism by
      addition of antimycin A to cells also increased Snf1 activity. Analysis of
      mutants indicated that the kinases Sak1, Tos3, and Elm1, which activate Snf1 in
      response to glucose limitation, are also required under other stress conditions.
      Each kinase sufficed for activation in response to stress, but Sak1 had the major
      role. In sak1Delta tos3Delta elm1Delta cells expressing mammalian
      Ca(2+)/calmodulin-dependent protein kinase kinase alpha, Snf1 was activated by
      both sodium ion and alkaline stress, suggesting that stress signals regulate Snf1
      activity by a mechanism that is independent of the upstream kinase. Finally, we
      showed that Snf1 protein kinase is regulated differently during adaptation of
      cells to NaCl and alkaline pH with respect to both temporal regulation of
      activation and subcellular localization. Snf1 protein kinase becomes enriched in
      the nucleus in response to alkaline pH but not salt stress. Such differences
      could contribute to specificity of the stress responses.

PMID- 17438334
TI  - The interleukin-22/STAT3 pathway potentiates expression of inducible nitric-oxide
      synthase in human colon carcinoma cells.
AB  - Inducible nitric-oxide synthase (iNOS) has been identified as a marker and
      mediator of disease in human colonic inflammation and carcinogenesis.
      Accordingly, identification of mediators that trigger iNOS in colon
      carcinoma/epithelial cells is an important topic of current research. Here we
      demonstrate that interleukin (IL)-22, a newly described member of the IL-10
      cytokine family, potently synergizes with interferon (IFN)-gamma for iNOS
      expression in human DLD-1 colon carcinoma cells. Detection of both IL-22 receptor
      chains and STAT3 phosphorylation proved robust IL-22 responsiveness of these
      cells. Short interfering RNA technology identified STAT3 as being crucial for up
      regulation of iNOS. Compared with IFNgamma, STAT1 phosphorylation by IL-22 was
      insufficient. IL-22 did not stabilize IL-1beta/tumor necrosis factor
      alpha/IFNgamma-induced iNOS mRNA. IL-22 also failed to amplify expression of the
      prototypic IFNgamma-inducible parameters IL-18-binding protein and CXCL-10,
      indicating that IL-22 is not a general amplifier of IFNgamma functions. This
      assumption is furthermore supported by the observation that IL-22 was unable to
      enhance cellular activation of the pro-inflammatory transcription factor nuclear
      factor-kappaB. In contrast, IL-22 increased iNOS promoter activation as detected
      by using DLD-1 cells stably transfected with a corresponding 16-kb promoter
      construct (pNOS2(16)-Luc). IL-22 likewise enhanced iNOS in Caco-2 colon carcinoma
      cells. With IL-22 we introduce a novel potent determinant of iNOS expression in
      human colon carcinoma/epithelial cells. Considering the eminent functions of
      STAT3 and iNOS in inflammation and carcinogenesis, IL-22 may represent a novel
      target for immunotherapeutic intervention.

PMID- 17438335
TI  - Disruption of the aspartate to heme ester linkage in human myeloperoxidase:
      impact on ligand binding, redox chemistry, and interconversion of redox
      intermediates.
AB  - In human heme peroxidases the prosthetic group is covalently attached to the
      protein via two ester linkages between conserved glutamate and aspartate residues
      and modified methyl groups on pyrrole rings A and C. Here, monomeric recombinant
      myeloperoxidase (MPO) and the variants D94V and D94N were produced in Chinese
      hamster ovary cell lines. Disruption of the Asp(94) to heme ester bond decreased
      the one-electron reduction potential E'(0) [Fe(III)/Fe(II)] from 1 to -55 mV at
      pH 7.0 and 25 degrees C, whereas the kinetics of binding of low spin ligands and
      of compound I formation was unaffected. By contrast, in both variants rates of
      compound I reduction by chloride and bromide (but not iodide and thiocyanate)
      were substantially decreased compared with the wild-type protein. Bimolecular
      rates of compound II (but not compound I) reduction by ascorbate and tyrosine
      were slightly diminished in D94V and D94N. The presented biochemical and
      biophysical data suggest that the Asp(94) to heme linkage is no precondition for
      the autocatalytic formation of the other two covalent links found in MPO. The
      findings are discussed with respect to the known active site structure of MPO and
      its complexes with ligands.

PMID- 17438336
TI  - Tumor necrosis factor-alpha stimulates focal adhesion kinase activity required
      for mitogen-activated kinase-associated interleukin 6 expression.
AB  - Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase that
      promotes cell migration, survival, and gene expression. Here we show that FAK
      signaling is important for tumor necrosis factor-alpha (TNFalpha)-induced
      interleukin 6 (IL-6) mRNA and protein expression in breast (4T1), lung (A549),
      prostate (PC-3), and neural (NB-8) tumor cells by FAK short hairpin RNA knockdown
      and by comparisons of FAK-null (FAK(-/-)) and FAK(+/+) mouse embryo fibroblasts.
      FAK promoted TNFalpha-stimulated MAPK activation needed for maximal IL-6
      production. FAK was not required for TNFalpha-mediated nuclear factor-kappaB or c
      Jun N-terminal kinase activation. TNFalpha-stimulated FAK catalytic activation
      and IL-6 production were inhibited by FAK N-terminal but not FAK C-terminal
      domain overexpression. Analysis of FAK(-/-) fibroblasts stably reconstituted with
      wild type or various FAK point mutants showed that FAK catalytic activity, Tyr
      397 phosphorylation, and the Pro-712/713 proline-rich region of FAK were required
      for TNFalpha-stimulated MAPK activation and IL-6 production. Constitutively
      activated MAPK kinase-1 (MEK1) expression in FAK(-/-) and A549 FAK short hairpin
      RNA-expressing cells rescued TNFalpha-stimulated IL-6 production. Inhibition of
      Src protein-tyrosine kinase activity or mutation of Src phosphorylation sites on
      FAK (Tyr-861 or Tyr-925) did not affect TNFalpha-stimulated IL-6 expression.
      Moreover, analyses of Src(-/-), Yes(-/-), and Fyn(-/-) fibroblasts showed that
      Src expression was inhibitory to TNFalpha-stimulated IL-6 production. These
      studies provide evidence for a novel Src-independent FAK to MAPK signaling
      pathway regulating IL-6 expression with potential importance to inflammation and
      tumor progression.

PMID- 17438337
TI  - ACAT2 stimulates cholesteryl ester secretion in apoB-containing lipoproteins.
AB  - Previous studies in nonhuman primates revealed a striking positive correlation
      between liver cholesteryl ester (CE) secretion rate and the development of
      coronary artery atherosclerosis. CE incorporated into hepatic VLDL is necessarily
      synthesized by ACAT2, the cholesterol-esterifying enzyme in hepatocytes. We
      tested the hypothesis that the level of ACAT2 expression, in concert with
      cellular cholesterol availability, affects the CE content of apolipoprotein B
      (apoB)-containing lipoproteins. In a model system of lipoprotein secretion using
      COS cells cotransfected with microsomal triglyceride transfer protein and
      truncated forms of apoB, ACAT2 expression resulted in a 3-fold increase in
      microsomal ACAT activity and a 4-fold increase in the radiolabeled CE content of
      apoB-lipoproteins. After cholesterol-cyclodextrin (Chol-CD) treatment, CE
      secretion was increased by 27-fold in ACAT2-transfected cells but by only 7-fold
      in control cells. Chol-CD treatment also caused the percentage of CE in the apoB
      lipoproteins to increase from 3% to 33% in control cells and from 16% to 54% in
      ACAT2-transfected cells. In addition, ACAT2-transfected cells secreted 3-fold
      more apoB than control cells. These results indicate that under all conditions of
      cellular cholesterol availability tested, the relative level of ACAT2 expression
      affects the CE content and, hence, the potential atherogenicity, of nascent apoB
      containing lipoproteins.

PMID- 17438338
TI  - Increased peripheral lipid clearance in an animal model of amyotrophic lateral
      sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common adult motor neuron
      disease, causing motor neuron degeneration, muscle atrophy, paralysis, and death.
      Despite this degenerative process, a stable hypermetabolic state has been
      observed in a large subset of patients. Mice expressing a mutant form of Cu/Zn
      superoxide dismutase (mSOD1 mice) constitute an animal model of ALS that, like
      patients, exhibits unexpectedly increased energy expenditure. Counterbalancing
      for this increase with a high-fat diet extends lifespan and prevents motor neuron
      loss. Here, we investigated whether lipid metabolism is defective in this animal
      model. Hepatic lipid metabolism was roughly normal, whereas gastrointestinal
      absorption of lipids as well as peripheral clearance of triglyceride-rich
      lipoproteins were markedly increased, leading to decreased postprandial
      lipidemia. This defect was corrected by the high-fat regimen that typically
      induces neuroprotection in these animals. Together, our findings show that energy
      metabolism in mSOD1 mice shifts toward an increase in the peripheral use of
      lipids. This metabolic shift probably accounts for the protective effect of
      dietary lipids in this model.

PMID- 17438339
TI  - Effects of apoA-V on HDL and VLDL metabolism in APOC3 transgenic mice.
AB  - Apolipoprotein A-V (apoA-V) and apoC-III are exchangeable constituents of VLDL
      and HDL. ApoA-V counteracts the effect of apoC-III on triglyceride (TG)
      metabolism with poorly defined mechanisms. To better understand the effects of
      apoA-V on TG and cholesterol metabolism, we delivered apoA-V cDNA into livers of
      hypertriglyceridemic APOC3 transgenic mice by adenovirus-mediated gene transfer.
      In response to hepatic apoA-V production, plasma TG levels were reduced
      significantly as a result of enhanced VLDL catabolism without alternations in
      VLDL production. This effect was associated with reduced apoC-III content in
      VLDL. Increased apoA-V production also resulted in decreased apoC-III and
      increased apoA-I content in HDL. Furthermore, apoA-V-enriched HDL was associated
      with enhanced LCAT activity and increased cholesterol efflux. This effect, along
      with apoE enrichment in HDL, contributed to HDL core expansion and alpha-HDL
      formation, accounting for significant increases in both the number and size of
      HDL particles. As a result, apoA-V-treated APOC3 transgenic mice exhibited
      decreased VLDL-cholesterol and increased HDL-cholesterol levels. ApoA-V-mediated
      reduction of apoC-III content in VLDL represents an important mechanism by which
      apoA-V acts to ameliorate hypertriglyceridemia in adult APOC3 transgenic mice. In
      addition, increased apoA-V levels accounted for cholesterol redistribution from
      VLDL to larger HDL particles. These data suggest that in addition to its TG
      lowering effect, apoA-V plays a significant role in modulating HDL maturation and
      cholesterol metabolism.

PMID- 17438340
TI  - Diabetes or peroxisome proliferator-activated receptor alpha agonist increases
      mitochondrial thioesterase I activity in heart.
AB  - Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a
      transcriptional regulator of the expression of mitochondrial thioesterase I (MTE
      I) and uncoupling protein 3 (UCP3), which are induced in the heart at the mRNA
      level in response to diabetes. Little is known about the regulation of protein
      expression of MTE-I and UCP3 or about MTE-I activity; thus, we investigated the
      effects of diabetes and treatment with a PPAR alpha agonist on these parameters.
      Rats were either made diabetic with streptozotocin (55 mg/kg ip) and maintained
      for 10-14 days or treated with the PPAR alpha agonist fenofibrate (300 mg/kg/day)
      for 4 weeks. MTE-I and UCP3 protein expression, MTE-1 activity, palmitate export,
      and oxidative phosphorylation were measured in isolated cardiac mitochondria.
      Diabetes and fenofibrate increased cardiac MTE-I mRNA, protein, and activity (
      approximately 4-fold compared with controls). This increase in activity was
      matched by a 6-fold increase in palmitate export in fenofibrate-treated animals,
      despite there being no effect in either group on UCP3 protein expression. Both
      diabetes and fenofibrate caused significant decreases in state III respiration of
      isolated mitochondria with pyruvate + malate as the substrate, but only diabetes
      reduced state III rates with palmitoylcarnitine. Both diabetes and specific PPAR
      alpha activation increased MTE-I protein, activity, and palmitate export in the
      heart, with little effect on UCP3 protein expression.

PMID- 17438341
TI  - The effect of visual performance feedback on teacher use of behavior-specific
      praise.
AB  - This study evaluated the effects of visual performance feedback (VPF) on teacher
      use of behavior-specific praise. In addition to receiving individual VPF,
      teachers participated in group consultation focused on increasing competence in
      the use of behavior-specific praise. Three general education elementary teachers
      and six students participated in the study. Classroom peer composite data were
      also collected. Teacher and student behaviors were monitored across baseline and
      VPF conditions in a multiple baseline design. The results indicated that VPF
      resulted in an increase in behavior-specific praise for participating students
      across all teachers relative to baseline. Additionally, teachers increased their
      use of behavior-specific praise with classroom peers. The findings highlight the
      need for direct assessment of intervention implementation and for the collection
      of peer data to identify collateral intervention effects.

PMID- 17438342
TI  - Outcome for children with autism who began intensive behavioral treatment between
      ages 4 and 7: a comparison controlled study.
AB  - This study extends findings on the effects of intensive applied behavior analytic
      treatment for children with autism who began treatment at a mean age of 5.5
      years. The behavioral treatment group (n = 13, 8 boys) was compared to an
      eclectic treatment group (n = 12, 11 boys). Assignment to groups was made
      independently based on the availability of qualified supervisors. Both behavioral
      and eclectic treatment took place in public kindergartens and elementary schools
      for typically developing children. At a mean age of 8 years, 2 months, the
      behavioral treatment group showed larger increases in IQ and adaptive functioning
      than did the eclectic group. The behavioral treatment group also displayed fewer
      aberrant behaviors and social problems at follow-up. Results suggest that
      behavioral treatment was effective for children with autism in the study.

PMID- 17438343
TI  - Are parent-reported outcomes for self-directed or telephone-assisted behavioral
      family intervention enhanced if parents are observed?
AB  - The study examined the effects of conducting observations as part of a broader
      assessment of families participating in behavior family intervention (BFI). It
      was designed to investigate whether the observations improve intervention
      outcomes. Families were randomly assigned to different levels of BFI or a
      waitlist control condition and subsequently randomly assigned to either
      observation or no-observation conditions. This study demonstrated significant
      intervention and observation effects. Mothers in more intensive BFI reported more
      improvement in their child's behavior and their own parenting. Observed mothers
      reported lower intensity of child behavior problems and more effective parenting
      styles. There was also a trend for less anger among mothers who were observed and
      evidence of an observation-intervention interaction for parental anger, with
      observed mothers in more intensive intervention reporting less anger compared to
      those not observed. Implications for clinical and research intervention contexts
      are discussed.

PMID- 17438344
TI  - The effectiveness of an experimental treatment when compared to care as usual
      depends on the type of care as usual.
AB  - In psychotherapy, effectiveness of an experimental treatment often is compared to
      care as usual. However, little if any attention has been paid to the
      heterogeneity of care as usual. The authors examined the effectiveness of
      manualized behavior therapy on school-aged disruptive behavior disordered (DBD)
      children in everyday clinical practice. A total of 77 DBD children (8-13 years)
      were randomly assigned to the Utrecht Coping Power Program (UCPP) condition or
      the care as usual condition. Care as usual consisted of family therapy (FT) or
      behavior therapy (BT). Decrease in parent-reported overt aggression was
      significantly larger in the UCPP condition than in the FT condition, but UCPP and
      BT did not differ significantly in this respect. The effect sizes of difference
      scores on other variables were more in favor of UCPP when compared to FT than to
      BT. The comparison of an experimental treatment to care as usual depends on the
      type of usual treatment.

PMID- 17438345
TI  - Individuals with mental illness can control their aggressive behavior through
      mindfulness training.
AB  - Verbal and physical aggression are risk factors for community placement of
      individuals with serious and persistent mental illness. Depending on the
      motivations involved, treatment typically consists of psychotropic medications
      and psychosocial interventions, including contingency management procedures and
      anger management training. Effects of a mindfulness procedure, Meditation on the
      Soles of the Feet , were tested as a cognitive behavioral intervention for verbal
      and physical aggression in 3 individuals who had frequently been readmitted to an
      inpatient psychiatric hospital owing to their anger management problems. In a
      multiple baseline across subjects design, they were taught a simple meditation
      technique, requiring them to shift their attention and awareness from the anger
      producing situation to the soles of their feet, a neutral point on their body.
      Their verbal and physical aggression decreased with mindfulness training; no
      physical aggression and very low rates of verbal aggression occurred during 4
      years of follow-up in the community.

PMID- 17438346
TI  - Errorless compliance training: success-focused behavioral treatment of children
      with Asperger syndrome.
AB  - Errorless compliance training is a noncoercive, success-focused approach to
      treatment of problem behavior in children. The intervention involves graduated
      exposure of a child to increasingly more challenging requests at a slow enough
      rate to ensure that noncompliance rarely occurs, providing parents with many
      opportunities to reinforce cooperative responses and rendering punishment
      unnecessary. The authors evaluated this approach with three boys with
      characteristics of Asperger syndrome. Mothers first delivered a range of requests
      to their children and recorded child responses. For each child, the authors
      calculated compliance probability for all requests and categorized them into four
      probability levels, from those yielding high compliance (Level 1) to those that
      commonly led to opposition (Level 4). Treatment began with delivery of Level 1
      requests. Requests from Levels 2 through 4 were faded in sequentially over
      several weeks. All three children demonstrated substantial generalized
      improvement in compliance.

PMID- 17438347
TI  - An HIV-preventive intervention for youth living with HIV.
AB  - As the number of youth infected with HIV rises, secondary prevention programs are
      needed to help youth living with HIV meet three goals: (a) increase self-care
      behaviors, medical adherence, and health-related interactions; (b) reduce
      transmission acts; and (c) enhance their quality of life. This article describes
      an intervention program for youth living with HIV. Youth engage in small-group
      activities with other infected peers to modify their behavioral patterns. The
      intervention aims to (a) reduce substance use and sexual behaviors that may
      transmit or enhance transmission of the HIV virus; (b) reduce negative impacts of
      substance use on seeking and utilizing health care, assertiveness, and adherence
      to health regimens; and (c) enhance the quality of life to maintain behavior
      changes over time. Interventions that target youth living with HIV are warranted.
      A variety of delivery strategies are discussed for secondary interventions.

PMID- 17438348
TI  - Immunohistochemical expression of RARalpha, RARbeta, and Cx43 in breast tumor
      cell lines after treatment with lycopene and correlation with RT-QPCR.
AB  - Lycopene, the major carotenoid found in tomatoes, is a potent antioxidant
      associated with the prevention of degenerative diseases such as breast cancer.
      This effect could be due to the interaction between lycopene and retinoic acid
      receptors as well as the stimulation of gap junction communication and synthesis
      of connexin 43. The expression of the RARalpha, RARbeta, and Cx43 proteins was
      analyzed using immunohistochemistry in two breast cancer cell lines, MCF-7 and
      MDA-MB-231, and in a fibrocystic dystrophy cell line, MCF-10a, after a 48-hr
      exposure to 10 microM lycopene. A real-time quantitative PCR analysis was then
      performed to measure mRNA expression. RARalpha and Cx43 expression were increased
      at both mRNA and protein levels in two breast cell lines.

PMID- 17438349
TI  - Immunohistochemical localization of cadherin and catenin adhesion molecules in
      the murine growth plate.
AB  - Mouse tibial growth plates were examined for the presence of adhesion molecules
      using immunohistochemistry and RT-PCR. All of the components of the classical
      cadherin/catenin complex (cadherin, alpha-, beta-, and gamma-catenin), as well as
      a heavy presence of p120, were identified in the murine growth plate. All of the
      major cadherins (1-5, 11, 13, and 15) were, for the first time, identified and
      localized in the murine growth plate. We have demonstrated that most of the
      cadherins and catenins reside in the zone of hypertrophy. Only alpha-catenin and
      E-, P-, R-, and VE-cadherin were found in all regions of the growth plate. The
      results for T-cadherin were inconclusive.

PMID- 17438350
TI  - Immunolocalization and cell expression of lung resistance-related protein (LRP)
      in normal and tumoral human respiratory cells.
AB  - Lung resistance-related protein (LRP) is an integral part of the multidrug
      resistance (MDR) phenotype involved in cell resistance toward xenobiotics or
      chemotherapy. The aim of this study was to compare the intracellular localization
      and cell expression of LRP in normal bronchial cells and their tumoral
      counterparts from non-small cell lung cancer (NSCLC). LRP expression was also
      investigated concurrently with DNA ploidy and chromosome 16 (lrp gene locus)
      aberrations. Confocal microscopy showed that LRP localization was exclusively
      intracytoplasmic regardless of the cell type and was never observed in the
      nuclear pore complex. Flow cytometry demonstrated a similar level of LRP
      expression in normal bronchial cells and in cancer cells from NSCLC samples. FISH
      analysis, performed to evaluate the number of chromosome 16 and lrp loci,
      demonstrated a significant gain of chromosome 16 in DNA aneuploid tumors.
      Furthermore, we did not find any link between LRP expression and DNA ploidy
      status or chromosome 16 number. These results suggest that LRP expression
      observed in NSCLC, maintained through the carcinogenesis process of respiratory
      cells, is not altered by the increased number of copies of chromosome 16 and
      probably controlled by mechanisms different from those of MRP1 expression,
      whereas both proteins are associated with the MDR phenotype.

PMID- 17438351
TI  - Ontogeny of intrinsic innervation in the human thymus and spleen.
AB  - The ontogeny of the innervation of human lymphoid organs has not been studied in
      detail. Our aim was to assess the nature and distribution of parenchymal nerves
      in human fetal thymus and spleen. We used the peroxidase immunohistochemical
      technique with antibodies specific to neuron-specific enolase (NSE),
      neurofilaments (NF), PGP9.5, S100 protein, and tyrosine hydroxylase (TH) and
      evaluated our results with image analysis. In human fetal thymus, NSE-, NF-, S100
      , PGP9.5-, and TH-positive nerves were identified associated with large blood
      vessels from 18 gestational weeks (gw) onwards, increasing in density during
      development. Their branches penetrated the septal areas at 20 gw, reaching the
      cortex and the corticomedullary junction between 20 and 23 gw. Few nerve fibers
      were seen in the medulla in close association with Hassall's corpuscles. In human
      fetal spleen, NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers were
      localized in the connective tissue surrounding the splenic artery at 18 gw.
      Perivascular NSE-, NF-, S100-, PGP9.5-, and TH-positive nerve fibers were seen
      extending into the white pulp, mainly in association with the central artery and
      its branches, increasing in density during gestation. Scattered NSE-, NF-, S100-,
      PGP9.5-, and TH-positive nerve fibers and endings were localized in the red pulp
      from 18 gw onward. The predominant perivascular distribution of most parenchymal
      nerves implies that thymic and splenic innervation may play an important
      functional role during intrauterine life.

PMID- 17438352
TI  - Sarcoglycan subcomplex expression in normal human smooth muscle.
AB  - The sarcoglycan complex (SGC) is a multimember transmembrane complex interacting
      with other members of the dystrophin-glycoprotein complex (DGC) to provide a
      mechanosignaling connection from the cytoskeleton to the extracellular matrix.
      The SGC consists of four proteins (alpha, beta, gamma, and delta). A fifth
      sarcoglycan subunit, epsilon-sarcoglycan, shows a wider tissue distribution.
      Recently, a novel sarcoglycan, the zeta-sarcoglycan, has been identified. All
      reports about the structure of SGC showed a common assumption of a tetrameric
      arrangement of sarcoglycans. Addressing this issue, our immunofluorescence and
      molecular results showed, for the first time, that all sarcoglycans are always
      detectable in all observed samples. Therefore, one intriguing possibility is the
      existence of a pentameric or hexameric complex considering zeta-sarcoglycan of
      SGC, which could present a higher or lower expression of a single sarcoglycan in
      conformity with muscle type--skeletal, cardiac, or smooth--or also in conformity
      with the origin of smooth muscle.

PMID- 17438353
TI  - Localization of sulfonylurea receptor subunits, SUR2A and SUR2B, in rat heart.
AB  - To understand the possible functions and subcellular localizations of
      sulfonylurea receptors (SURs) in cardiac muscle, polyclonal anti-SUR2A and anti
      SUR2B antisera were raised. Immunoblots revealed both SUR2A and SUR2B expression
      in mitochondrial fractions of rat heart and other cellular fractions such as
      microsomes and cell membranes. Immunostaining detected ubiquitous expression of
      both SUR2A and SUR2B in rat heart in the atria, ventricles, interatrial and
      interventricular septa, and smooth muscles and endothelia of the coronary
      arteries. Electron microscopy revealed SUR2A immunoreactivity in the cell
      membrane, endoplasmic reticulum (ER), and mitochondria. SUR2B immunoreactivity
      was mainly localized in the mitochondria as well as in the ER and cell membrane.
      Thus, SUR2A and SUR2B are not only the regulatory subunits of sarcolemmal K(ATP)
      channels but may also function as regulatory subunits in mitochondrial K(ATP)
      channels and play important roles in cardioprotection.

PMID- 17438354
TI  - What does DNA methylation surrogate?

PMID- 17438355
TI  - Risk prediction of gastric cancer by analysis of aberrant DNA methylation in non
      neoplastic gastric epithelium.
AB  - BACKGROUND: Aberrant DNA methylation is one of the major events in
      carcinogenesis. Promoter DNA methylation is also present in various non
      neoplastic tissues including gastric epithelium as age-related phenomenon,
      suggesting that it occurs early in the process of tumorigenesis. AIM: We aimed to
      clarify the relationship of aberrant DNA methylation in non-neoplastic gastric
      epithelia with the risk of gastric cancer, Helicobactor pylori infection, and the
      degree of H. pylori-induced gastritis. METHODS: 89 patients enrolled in this
      study. The status of aberrant DNA methylation was compared in two groups of
      patients: 43 cases with gastric cancer (mean age 65.9 years [29-91], F:M = 0.30,
      intestinal type [n = 25], diffuse type [n = 18]) and 46 age- and sex-matched
      patients without gastric cancer (peptic ulcer diseases [n = 11], gastritis [n =
      35]) as a control group. Genomic DNA was extracted directly from non-neoplastic
      epithelia of antral biopsies obtained by endoscopy. The promoter methylation
      status of the p14 and p21 genes was determined by methylation-specific-polymerase
      chain reaction (MSP). The promoter methylation status of the p16 gene was
      quantified by digital densitographic analysis following MSP. The degree of
      gastritis in the antrum was assessed according to the updated Sydney system. The
      PG I/II ratio was calculated based on the data of serum PG I and PG II levels
      measured by radioimmunoassay. RESULTS: In all 89 subjects, CpG island methylation
      was found in 25.8% for p14, 52.8% for p16, 1.1% for p21. Among non-cancer
      patients, the methylation frequency of the p14 gene was significantly higher in
      H. pylori-positive than in H. pylori-negative patients (38.5 vs. 10.0%, p =
      0.03). The mean (+/- SD) methylation levels of the p16 gene in non-neoplastic
      gastric epithelium was significantly higher in gastric cancer cases both in all
      patients and in H. pylori-positive patients (0.45 +/- 0.31 vs. 0.20 +/- 0.17; p =
      0.019, 0.45 +/- 0.31 vs. 0.20 +/- 0.17; p = 0.016, respectively). The methylation
      level of the p16 gene was also associated with the presence of intestinal-type
      gastric cancer (p = 0.017). The methylation level of the p16 gene was
      significantly higher in patients with intestinal metaplasia (IM) than those
      without (p = 0.04). Furthermore, the methylation level of the p16 gene was
      correlated with lower PG l/ll ratio (p = 0.04). The methylation of the p21gene
      was found in only 1 patient with gastric cancer. CONCLUSIONS: Our data suggest
      that promoter of the p14 gene may be one of the specific regions whose
      methylation is closely associated with H. pylori infection. Methylation levels of
      the p16 gene seem to be accumulated in the progression of gastric mucosal atrophy
      and IM, and thus may be associated with the presence of gastric cancer especially
      for intestinal-type histopathology.

PMID- 17438356
TI  - Reviewing the structural features of autologous platelet-leukocyte gel and
      suggestions for use in surgery.
AB  - The therapeutic use of autologously prepared platelet-leukocyte gel (PLG) is a
      relatively new technology which might stimulate and accelerate soft-tissue and
      bone healing. The effectiveness of this procedure lies in the exogenous delivery
      of a wide range of platelet growth factors, intentionally released from
      autologously prepared PLG. The rationale to employ this technique is to mimic
      physiological wound healing and reparative tissue processes. Despite an increase
      in clinical PLG applications, the structures and kinetics of this biological
      material have not been completely examined. Electron microscopic imaging was
      performed to evaluate platelet-leukocyte gel structures. Furthermore, directions
      for PLG application are presented, based on results from published articles in
      various surgical disciplines. In conclusion, PLG can be useful in a wide range of
      clinical applications to enhance healing following surgical procedures, since
      exogenous applied PLG releases instantly platelet growth factors, in the presence
      of leukocytic cells.

PMID- 17438357
TI  - Role of heparin on TNF-alpha and IL-6 levels in liver regeneration after partial
      hepatic resection.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of heparin on TNF
      alpha and interleukin (IL)-6 levels and the complement system in liver
      regeneration in a murine model. MATERIALS AND METHODS: 32 Wistar albino female
      rats weighing between 180 and 250 g were included in the study. The rats were
      divided into four groups as follows: group 1, treated with partial (50%)
      hepatectomy and intravenous heparin 1,000 IU/kg in repeated daily doses; group 2,
      treated with sham operation and intravenous heparin 1,000 IU/kg in repeated daily
      doses; group 3, treated with partial (50%) hepatectomy, and group 4 (controls),
      treated with only sham operation. Before the surgical intervention and after a
      general anesthetic had been administered to all rats, blood was taken from the
      left ventricle of each rat, and each sample was assessed to determine total
      complement hemolytic activity (CH(50)/ml). On the 5th postoperative day, blood
      was taken to assess CH(50) activity and the levels of TNF-alpha and IL-6 via
      ELISA. Each rat was then killed by decapitation after which gravimetric analysis
      and immunohistochemical staining for proliferating cell nuclear antigen (PCNA)
      were performed. RESULTS: Serum CH(50) activity of group 1 was 4% as compared to
      51% in group 3 (p = 0.01). The serum TNF-alpha level of group 1 was 43 pg/ml as
      compared to 86 pg/ml in group 3 (p = 0.002). The serum IL-6 level of group 1 was
      19 pg/ml as compared to 44 pg/ml in group 3 (p = 0.02). The serum IL-6 level of
      group 2 was 4 pg/ml as compared to 44 pg/ml in group 3 (p = 0.005). According to
      the results of gravimetric analysis, the mean regeneration rate of group 1 was
      4.4% as compared to 22% of group 3 (p = 0.001). The mean PCNA index values of
      group 2 was the highest of all groups (p = 0.01). However, the mean PCNA index
      value of group 1 was the lowest of all groups (p = 0.01). CONCLUSION: Because of
      its anti-inflammatory action via the complement system, heparin produced an
      unfavorable effect on liver regeneration.

PMID- 17438358
TI  - Favorable tissue effects of quantum molecular resonance device (Vesalius)
      compared with standard electrocautery. A novel paradigm in lung surgery.
AB  - BACKGROUND: Electrosurgical devices are largely employed in thoracic surgery but
      their use is burdened by extensive necrosis and second intention healing.
      METHODS: A rat model of thoracotomy was performed on 46 adult male rats using a
      standard electrocautery or a new quantum molecular resonance (QMR) instrument
      called Vesalius. Skin, muscle and lung specimens were obtained immediately and 2
      weeks after surgery to evaluate acute and late effects. RESULTS: Both in the
      short- and long-term study, Vesalius produced less severe tissue damage than that
      of standard electrocautery. CONCLUSIONS: The use of the QMR device may provide an
      alternative to gold-standard electrosurgical devices in thoracic surgery.

PMID- 17438359
TI  - Neuregulin-1 attenuates neointimal formation following vascular injury and
      inhibits the proliferation of vascular smooth muscle cells.
AB  - Neuregulin-1 (NRG-1) is expressed in vascular endothelial cells, and its
      receptors are localized to the underlying smooth muscle cells. However, the role
      of NRG-1 in vascular function and injury is largely unknown. First, the
      expression of NRG-1 and its receptors (erbB receptors) was analyzed after balloon
      injury to the rat carotid artery. NRG-1 and erbB expression levels were low in
      uninjured vessels; however, NRG-1 and erbB4 were upregulated following injury. We
      then examined the effect of NRG-1 on neointimal formation following balloon
      injury. NRG-1 was administered by tail-vein injection prior to injury and every 2
      days following injury. Two weeks after injury, NRG-1-treated animals demonstrated
      a 50% reduction in lesion size compared with controls receiving the vehicle. To
      examine possible mechanisms for NRG-1 action, we examined its effects on vascular
      smooth muscle cell (VSMC) function. Rat VSMC cultures were pretreated with NRG-1
      for 24 h and then stimulated with platelet-derived growth factor. NRG-1
      significantly decreased platelet-derived growth factor-stimulated VSMC
      proliferation and migration. These findings suggest that NRG-1 may be a novel
      therapeutic candidate for the treatment of restenosis and atherosclerosis.

PMID- 17438360
TI  - The anti-apoptotic activity of albumin for endothelium is mediated by a partially
      cryptic protein domain and reduced by inhibitors of G-coupled protein and PI-3
      kinase, but is independent of radical scavenging or bound lipid.
AB  - Increased vascular disease occurs with low albumin (human serum albumin, HSA),
      possibly reflecting specific inhibition of endothelial apoptosis reported for
      tissue culture. Despite the reported specificity for endothelial protection by
      HSA, the high but physiological concentrations needed appear more consistent with
      non-specific low-affinity interactions. We reconcile this contradiction by
      demonstrating protection is mediated by a partially cryptic HSA protein domain,
      which becomes more exposed and active following cyanogen bromide fragmentation (p
      < 0.001). Also, although others reported HSA radical scavenging and bound lipids
      as important for inhibiting apoptosis in non-endothelial cell types, we
      demonstrate the protective effect for endothelium is unaffected when HSA radical
      scavenging is blocked by alkylation, or following delipidation. Further probing
      the mechanism responsible, we found that the G-coupled protein inhibitors
      pertussis toxin and suramin reduced protection of endothelium by HSA (p < 0.005),
      while the tyrosine kinase inhibitor genistein had no effect. Consistent with a
      role for phosphoinositide 3 kinase (PI3K) was inhibition by both wortmannin and
      LY294002 (p < 0.05), as well as phosphorylation of Akt, while MAP kinase
      inhibitors had no effect. We conclude the active site in HSA inhibiting
      endothelial apoptosis is partially cryptic, and acts via a G-coupled protein PI3K
      dependent mechanism.

PMID- 17438361
TI  - Activity of endothelium-derived hyperpolarizing factor is augmented in
      monocrotaline-induced pulmonary hypertension of rat lungs.
AB  - The mechanism of endothelium-dependent vasodilator signaling involves three
      components such as nitric oxide, prostacyclin, and endothelium-derived
      hyperpolarizing factor (EDHF). Although EDHF is distinct from nitric oxide and
      prostacyclin, it requires activation of Ca(2+)-sensitive K(+) channels (K(Ca))
      and cytochrome P(450) metabolites. However, the physiological role of EDHF in the
      pulmonary circulation is unclear. Thus, we tested if EDHF would regulate vascular
      tone in rat lungs of control and monocrotaline (MCT)-induced pulmonary
      hypertension. Inhibition of EDHF with a combination of K(Ca) blockers,
      charybdotoxin (50 nM) plus apamin (50 nM), increased baseline vascular tone in
      MCT-induced hypertensive lungs. Thapsigargin (TG; 100 nM), an inhibitor of Ca
      ATPase, caused greater EDHF-mediated vasodilation in MCT-induced hypertensive
      lungs. TG-induced vasodilation was abolished with the charybdotoxin-apamin
      combination. Sulfaphenazole (10 muM), a cytochrome P(450) inhibitor, reduced the
      TG-induced vasodilation in MCT-induced hypertensive lungs. RT-PCR analysis
      exhibited an increase in K(Ca) mRNA in MCT-treated lungs. These results indicate
      the augmentation of tonic EDHF activity, at least in part, through the alteration
      in cytochrome P(450) metabolites and the upregulation of K(Ca) expression in MCT
      induced pulmonary hypertension.

PMID- 17438362
TI  - Oxidation as a post-translational modification that regulates autophagy.
AB  - The toxicity associated with accumulation of reactive oxygen species (ROS) has
      led to the evolution of various defense strategies to overcome oxidative stress,
      including autophagy. This pathway is involved in the removal and degradation of
      damaged mitochondria and oxidized proteins. At low levels, however, ROS act as
      signal transducers in various intracellular pathways. In a recent study we
      described the role of ROS as signaling molecules in starvation-induced autophagy.
      We showed that starvation stimulates formation of ROS, specifically H(2)O(2), in
      the mitochondria. Furthermore, we identified the cysteine protease HsAtg4 as a
      direct target for oxidation by H(2)O(2), and specified a cysteine residue located
      near the HsAtg4 catalytic site as critical for this regulation. Here we focus on
      Atg4, the target of regulation, and discuss possible mechanisms for the
      regulation of this enzyme in the autophagic process.

PMID- 17438363
TI  - Nitric oxide-induced cell death in the heart: the role of autophagy.
AB  - There is unequivocal evidence of autophagy in the heart, both in human hearts
      from patients who experienced heart failure and in experimental models of
      myocardial ischemia and reperfusion. Whether autophagy is involved in the
      pathophysiology of these conditions is controversial as studies suggest
      inhibition of Beclin 1 can increase or decrease cardiomyocyte cell injury.
      Increased beclin 1 expression, however, has been consistently identified in
      myocardial ischemia/reperfusion. Because of the role of nitric oxide (NO) in
      myocardial ischemia/reperfusion as well as in heart failure, we sought to
      determine whether NO and its byproduct peroxynitrite alter the expression of some
      genes involved in autophagy in the heart. Neonatal mouse cardiomyocytes were
      treated with SIN-1 (3-morpholinosydnonimine), which releases NO and accelerates
      formation of peroxynitrite. Gene expression was evaluated using RNA labeled and
      hybridized to cDNA microarrays. SIN-1 treatment induced significant changes in
      five caspases. In contrast, there were no changes in three genes involved in
      autophagy, namely beclin 1, Atg5l and Atg12l. Several different time periods were
      examined; a short time period, 2h, to more closely model myocardial ischemia
      reperfusion and a long time period, 20 h, that more closely represents sustained
      injury. In summary, evidence to date suggests that NO is not involved in
      increased beclin 1 expression in ischemia/reperfusion injury in the heart and
      would be unlikely to account for the signs of autophagy in the hearts of patients
      with heart failure.

PMID- 17438364
TI  - Chaperone-mediated autophagy and aging: a novel regulatory role of lipids
      revealed.
AB  - A wide pool of cytosolic proteins is selectively degraded in lysosomes by
      chaperonemediated autophagy (CMA). Binding of these proteins to a receptor at the
      lysosomal membrane is the limiting step in CMA. Levels of this receptor are
      tightly regulated through changes in its degradation, multimeric organization and
      dynamic distribution between the lysosomal membrane and lumen. We have now
      reported that subcompartmentalization of the receptor in discrete lipid
      microdomains at the lysosomal membrane regulates its engagement in each of these
      processes-degradation, multimerization and membrane retrieval. Changes in the
      lipid composition of the membrane thus affect the dynamics of the receptor and,
      consequently, CMA activity. As an example of CMA dysfunction resulting from
      perturbation of the lipid composition of the lysosomal membrane, we discuss here
      a second study in which we analyzed the changes in the dynamics of the receptor
      during aging. CMA activity decreases with age primarily due to a decrease in the
      levels of the CMA receptor at the lysosomal membrane. Now we have found that age
      related alterations in the lipid composition of the discrete microdomains at the
      lysosomal membrane are behind the reduced lysosomal levels of the receptor and,
      consequently, the declined CMA activity that occurs during aging.

PMID- 17438365
TI  - Macroautophagy as a pathomechanism in sporadic inclusion body myositis.
AB  - Skeletal muscle fibers show a high level of constitutive and starvation-induced
      macroautophagy. Sporadic Inclusion Body Myositis (sIBM) is the most common
      acquired skeletal muscle disease in patients above the age of 50 years and is
      characterized by inflammation and intracellular accumulation of aggregate-prone
      proteins such as amyloid precursor protein (APP)/beta-amyloid,
      hyperphosphorylated tau, and presenilin. In a recent study, we found that muscle
      fibers of sIBM patients show increased frequencies of Atg8/LC3(+) autophagosomes
      and that intracellular APP/beta-amyloid colocalized with Atg8/LC3 in degenerating
      fibers. Colocalization of APP/beta-amyloid with LC3(+) autophagosomes was further
      associated with upregulation of major histocompatibility complex (MHC) class I
      and class II molecules and T cell infiltration. These findings indicate that
      APP/beta-amyloid is a substrate for autophagy in skeletal muscle fibers and
      suggest that degradation of aggregate-prone proteins via macroautophagy can be
      linked with both immune-mediated and degenerative tissue damage. A better
      understanding of this pathway in skeletal muscle and in the inflammatory
      environment of sIBM might provide a rationale for novel therapeutic strategies
      targeting pathogenic protein aggregation.

PMID- 17438366
TI  - BH3-only proteins and BH3 mimetics induce autophagy by competitively disrupting
      the interaction between Beclin 1 and Bcl-2/Bcl-X(L).
AB  - Beclin 1 has recently been identified as novel BH3-only protein, meaning that it
      carries one Bcl-2-homology-3 (BH3) domain. As other BH3-only proteins, Beclin 1
      interacts with anti-apoptotic multidomain proteins of the Bcl-2 family (in
      particular Bcl-2 and its homologue Bcl-X(L)) by virtue of its BH3 domain, an
      amphipathic alpha-helix that binds to the hydrophobic cleft of Bcl-2/Bcl-X(L).
      The BH3 domains of other BH3-only proteins such as Bad, as well as BH3-mimetic
      compounds such as ABT737, competitively disrupt the inhibitory interaction
      between Beclin 1 and Bcl-2/Bcl-X(L). This causes autophagy of mitochondria
      (mitophagy) but not of the endoplasmic reticulum (reticulophagy). Only ER
      targeted (not mitochondrion-targeted) Bcl-2/Bcl-X(L) can inhibit autophagy
      induced by Beclin 1, and only Beclin 1-Bcl-2/Bcl-X(L) complexes present in the ER
      (but not those present on heavy membrane fractions enriched in mitochondria) are
      disrupted by ABT737. These findings suggest that the Beclin 1-Bcl-2/Bcl-X(L)
      complexes that normally inhibit autophagy are specifically located in the ER and
      point to an organelle-specific regulation of autophagy. Furthermore, these data
      suggest a spatial organization of autophagy and apoptosis control in which BH3
      only proteins exert two independent functions. On the one hand, they can induce
      apoptosis, by (directly or indirectly) activating the mitochondrion
      permeabilizing function of pro-apoptotic multidomain proteins from the Bcl-2
      family. On the other hand, they can activate autophagy by liberating Beclin 1
      from its inhibition by Bcl-2/Bcl-X(L) at the level of the endoplasmic reticulum.

PMID- 17438367
TI  - Relationship between autophagy and apoptotic cell death in human neuroblastoma
      cells treated with paraquat: could autophagy be a "brake" in paraquat-induced
      apoptotic death?
AB  - Paraquat (PQ) (1, 1'-dimethyl-4, 4'-bipyridinium dichloride), a widely used
      herbicide, has been suggested as a potential etiologic factor for the development
      of Parkinson's disease (PD). In neurons from patients with PD display
      characteristics of autophagy, a degradative mechanism involved in the recycling
      and turnover of cytoplasmic constituents from eukaryotic cells. Low
      concentrations of paraquat have been recently found to induce autophagy in human
      neuroblastoma cells, and ultimately the neurons succumb to apoptotic death.
      Whereas caspase inhibition retarded cell death, autophagy inhibition accelerated
      the apoptotic cell death induced by paraquat. These findings suggest a
      relationship between autophagy and apoptotic cell death in human neuroblastoma
      cells treated with paraquat and open a new line of investigation to advance our
      knowledge regarding the origin of PD.

PMID- 17438368
TI  - The inhibitory effects of nanosize delivery system for antisense oligonucleotide
      of hTERT on EC9706 cells.
AB  - A nanosize delivery system (NDS) for oligonucleotides (ODNs) was established, and
      the effects mediated by NDS containing the antisense oligonucleotides (ASODNs)
      for hTERT mRNA on EC9706 cells were investigated by methyl thiazolyl tetrazolium
      (MTT) assay, RT-PCR, immunohistochemistry and flow cytometry. The inhibitory
      effects of ASODNs-NDS on EC9706 cells proliferation had a concentration-dependent
      and time-dependent manner. There was a significant difference in inhibitory rate
      between cell control group and ASODNs (I --> VIII)-NDS groups (p < 0.05).
      However, no significant difference was found between cell control group and NDS
      group, SODN (sense oligonucleotide) group or ASODNs group (p > 0.05). After
      transfection of ASODNs-NDS for 72 h, the level of hTERT mRNA decreased observably
      compared with cell control group (p < 0.05), and cells apoptosis appeared in the
      ASODNs-NDS groups. The ASODNs complementary to the sites to which Sp1 and c-myc
      bind had stronger effects on EC9706 cell proliferation and apoptosis.

PMID- 17438369
TI  - The RUNX2 transcription factor cooperates with the YES-associated protein, YAP65,
      to promote cell transformation.
AB  - The Runt box domain DNA-binding transcription factors (RUNX) play key roles in
      hematopoietic, bone, and gastric development. These factors regulate angiogenesis
      and tumorigenic events, functioning as either activators or repressors of target
      genes. Although RUNX2 is an essential bone maturation factor, it has also been
      found to promote transformation in vivo and cell proliferation in vitro, perhaps
      by associating with specific coactivators or corepressors. Adenoviral-mediated
      overexpression of dominant negative RUNX2 or specific reduction of RUNX2 with RNA
      interference inhibits cell proliferation. To determine whether RUNX2 also plays a
      role in cell transformation, RUNX2 interactions with the coactivator Yes
      associated protein (YAP65) were examined. RUNX2 associated with YAP65 via a
      proline-rich segment in the C-terminal domain (PPPY) and coexpression of RUNX2
      and YAP65 significantly increased foci formation and anchorage-independent growth
      relative to each factor alone. However, in contrast to wild-type RUNX2, a mutant
      RUNX2(P409A), which does not bind YAP65, did not cooperate with YAP65 to promote
      anchorage-independent growth. RUNX2 is a strong repressor of the cyclin-dependent
      kinase inhibitor p21(CIP1), which is known to mediate cell transformation.
      Overexpression of YAP65 prevented RUNX2-dependent downregulation of p21(CIP1)
      protein expression while promoting cell transformation. The RUNX2(P409A) mutant
      retained the ability to bind DNA and repress the p21(CIP1) promoter as shown by
      DNA precipitation and luciferase-reporter assays, respectively, but was not able
      to relieve repression of the p21(CIP1) promoter. Therefore, these results reveal
      a novel function of the RUNX2 and YAP65 interaction in oncogenic transformation
      that may be mediated by modulation of p21(CIP1) protein expression.

PMID- 17438370
TI  - Inflammation in obesity is the common link between defects in fatty acid
      metabolism and insulin resistance.
AB  - Over the past two decades increases in obesity, due to high caloric intakes and
      immobilizing technologies, has led to a surge in type 2 diabetes. In obesity
      elevated circulating fatty acids set-off a pro-inflammatory cascade that
      increases the production of tumour necrosis factor-alpha(TNFalpha) from
      macrophages. Obesity is associated with blunted skeletal muscle fatty acid
      oxidation, accumulation of bioactive lipids and insulin resistance. The factors
      contributing to defects in fatty acid metabolism are not understood but new data
      demonstrates that increased TNFalpha in obesity increases protein phosphatase 2C
      (PP2C), which in turn suppresses the activity of AMP-activated protein kinase
      (AMPK), a critical regulator of energy metabolism.(1) These data identify a novel
      mechanism by which inflammation in obesity is a precursor to defects in skeletal
      muscle fatty acid oxidation that generates a vicious cycle exacerbating the
      development of insulin resistance.

PMID- 17438371
TI  - Detection and identification of transcription factors as interaction partners of
      alien in vivo.
AB  - Interacting proteins are often involved in the same cellular processes, and thus
      the identification of interacting partners of a given protein with unknown
      function may give insight into the physiological role of this protein. For the
      detection of protein-protein interactions of the corepressor Alien we used a
      proteomic approach comprising mass spectrometry and immunological techniques. We
      assessed solely endogenously expressed proteins. In this study we present for the
      first time that Alien is interacting within a network of proteins involved in
      transcriptional regulation, DNA repair, and cell cycle in vivo. In this way we
      detected protein interactions of Alien involving nucleophosmin, ERCC3, TRIP11, as
      well as CRSP3.

PMID- 17438372
TI  - High-throughput screening by RNA interference: control of two distinct types of
      variance.
AB  - The availability of genome-wide RNAi libraries has enabled researchers to rapidly
      assess the functions of thousands of genes; however the fact that these screens
      are run in living biological systems add complications above and beyond that
      normally seen in high-throughput screening (HTS). Specifically, error due to
      variance in both measurement and biology are large in such screens, leading to
      the conclusion that the majority of "hits" are expected to be false positives.
      Here, we outline basic guidelines for screen development that will help the
      researcher to control these forms of variance. By running a large number of
      positive and negative control genes, error of measurement can be accurately
      estimated and false negatives reduced. Likewise, by using a complex readout for
      the screen, which is not easily mimicked by other biological pathways and
      phenomena, false positives, can be minimized. By controlling variance in these
      ways, the researcher can maximize the utility of genome-wide RNAi screening.

PMID- 17438374
TI  - Recent arguments against germ cell renewal in the adult human ovary: is an
      absence of marker gene expression really acceptable evidence of an absence of
      oogenesis?
AB  - In 2004, a study from our lab published in the journal Nature reignited a
      worldwide debate over the validity of the dogma that mammalian females are
      incapable of oocyte and follicle production during postnatal life. Amidst
      widespread skepticism, we forged ahead and published a second study in 2005 in
      the journal Cell, which not only reaffirmed with different experimental
      approaches that this dogma is invalid but also identified cells in bone marrow
      (BM) and blood of adult female mice that could generate oocytes contained within
      immature follicles in the ovaries of recipient females following transplantation.
      Although this work has been the subject of extensive critical commentary as well,
      two recent reports from others have confirmed the germline potential of adult BM
      derived cells in mice. Further, independent corroboration of the results and
      conclusions presented in our earlier Nature paper is also now available. However,
      three papers have been published that purportedly question our work and
      conclusions. The first is a paper by Eggan et al. published in the journal
      Nature, which attempts to draw conclusions about the germline potential of BM
      derived cells after focusing solely on ovulated eggs while ignoring what may be
      occurring at the level of oogenesis in the ovaries. The second, from Veitia and
      colleagues, attempts to draw the same conclusions as Eggan et al. from a single
      clinical case report of a female Fanconi anemia patient who conceived a
      genetically-related daughter after allogeneic bone marrow transplantation. The
      third is a report from Liu et al. just released in the journal Developmental
      Biology that claims to provide evidence refuting the possibility that adult
      female mammals produce new oocytes. However, all of the data presented in this
      latter report are derived from gene expression studies that the authors say fail
      to show the occurrence of meiosis or germ cell mitosis in adult human ovaries.
      Given that more than three years have passed since our initial study challenging
      the dogma was published, it is our belief that continuing arguments against the
      possibility of postnatal oogenesis in mammals should be based on more rigorous
      experimental approaches than simply an absence of evidence, especially from gene
      expression analyses. Further, the interpretations offered by Liu et al. of their
      results are not as straightforward as they contend since some of their data can
      also be viewed as supportive of postnatal oogenesis in reproductive age women.

PMID- 17438373
TI  - Regulation of SCF(SKP2) ubiquitin E3 ligase assembly and p27(KIP1) proteolysis by
      the PTEN pathway and cyclin D1.
AB  - The PTEN tumor suppressor functions as a phosphatase of phosphatidylinositol
      3,4,5-trisphosphate (PIP3) and negatively regulates the PI 3-kinase signaling
      pathway. Our previous studies showed that PTEN expression causes accumulation of
      cyclin-dependent kinase inhibitor p27(Kip1) and G(1) cell cycle arrest. Here, we
      show that PTEN negatively regulates expression of cyclin D1 and that cyclin D1
      plays a unique role in p27 proteolysis. Coexpression of cyclin D1, but not cyclin
      E, is sufficient to restore p27 levels in PTEN-expressing cells. Conversely, loss
      of cyclin D1 by siRNA causes p27 accumulation. Silencing of the cyclin D1 gene or
      inhibition of the PI 3-kinase pathway prevents formation of the SCF(SKP2)
      complex, with a simultaneous increase in CUL1 binding to CAND1. CAND1-CUL1
      binding is known to block the accessibility of CUL1 to SKP1 and (SKP2). We have
      found that CUL1 is less neddylated in cells that have lost cyclin D1 expression.
      Using an in vitro extract system, we found that the extracts prepared from cells
      lacking cyclin D1 have reduced activity to neddylate CUL1, in a manner similar to
      extracts from cells treated with a PI 3-kinase inhibitor or in G(0) resting
      cells. Consistently, the steady state levels of CUL1 neddylation were found lower
      under these conditions. Our studies reveal that PTEN/PI 3-kinase signaling and
      cyclin D1 control a novel pathway that regulates assembly of the SCF(SKP2)
      complex by modulating cullin neddylation and CAND1 binding at the G(1)/S cell
      cycle transition.

PMID- 17438375
TI  - The role of angiopoietin 2 in hyperoxia-induced acute lung injury.
AB  - Hyperoxia-induced acute lung injury (HALI) is characterized by an influx of
      inflammatory cells, increased pulmonary permeability, endothelial and epithelial
      cell death. In a murine model and in vitro, we found Angiopoietin 2 to be a
      critical mediator of lung oxidant injury, inflammation, edema, and regulator of
      necrotic cell death pathways. The clinical significance of our findings was
      highlighted by the detection of increased Angiopoietin 2 levels in patients with
      ALI.

PMID- 17438376
TI  - Minimally invasive valve surgery.
AB  - Minimally invasive heart valve surgery has evolved significantly over the past 10
      years and now comprises safe and efficient operations for most patients. The main
      goals of minimally invasive heart valve surgery are to reduce surgical trauma,
      increase patient satisfaction, reduce morbidity, and lower costs while still
      providing durable and safe valve repair or replacement. After a decade of
      refinements, studies have shown that minimally invasive heart valve surgery is a
      safe and effective procedure with similar if not improved perioperative morbidity
      and mortality rates compared with conventional valve surgery. Patients derive a
      variety of tangible benefits from these new surgical approaches, including less
      pain, shorter lengths of hospital stay, and faster return to preoperative
      functional levels. Minimally invasive heart valve surgery should be an option for
      any patient undergoing heart valve surgery today.

PMID- 17438377
TI  - Nutriceuticals in cardiovascular disease: psyllium.
AB  - In recent years, there has been a growing interest in the use of dietary fiber in
      health maintenance and disease prevention. A deficiency of fiber in the Western
      diet may be contributing to the current epidemics of diabetes mellitus, coronary
      artery disease (CAD), and colonic cancer. The awareness of fiber as a dietary
      supplement may have contributed to the reported 30% decline in death rate from
      CAD observed over the past 15 years. Psyllium is a soluble gel-forming fiber that
      has been shown to bind to the bile acids in the gut and prevent their normal
      reabsorption, similar to the bile acid sequestrant drugs. Psyllium is useful as
      an adjunct to dietary therapy (step 1 or step 2 American Heart Association [AHA]
      diet) in the treatment of patients with mild-to-moderate hypercholesterolemia. In
      combination with other cholesterol-lowering drugs, such as statins, psyllium
      provides an added benefit on cholesterol lowering, and is well tolerated and cost
      effective.

PMID- 17438378
TI  - On the value of doing nothing: anger and cardiovascular disease in clinical
      practice.
AB  - Type A behavior, anger, and hostility have all been described as psychosocial
      risk factors or potential risk factors for cardiovascular disease (CVD). However,
      in the populations evaluated, the methods used to measure these traits and the
      endpoints used to determine outcomes have varied widely. The results of these
      studies have also been quite disparate. The present article reviews data from all
      the existing quantitative (meta-analytic) and qualitative systematic review
      articles that cover this topic, using the Database of Abstracts of Reviews of
      Effects (DARE) criteria. We conclude that the existing data do not support a
      meaningful clinical relationship between current measurements of these traits and
      the development of CVD.

PMID- 17438379
TI  - Clinical significance of minor nonspecific ST-segment and T-wave abnormalities in
      asymptomatic subjects: a systematic review.
AB  - The purpose of the study is to examine the prevalence and significance of minor
      nonspecific ST-segment and T-wave abnormalities (NSSTTA) in the prediction of
      future cardiovascular disease (CVD) events. Minor NSSTTA are commonly encountered
      in clinical practice. To date, there have been no systematic reviews focusing on
      the prevalence and prognostic importance of these findings. Literature searches
      of MEDLINE (1966-2005) were supplemented with searches of bibliographies from key
      articles. We focused on isolated minor NSSTTA in healthy middle-aged or elderly
      populations, including men, women, blacks, and whites, and the association of
      isolated minor NSSTTA with incident cardiovascular and coronary events. Isolated
      minor NSSTTA are common in middle-aged white men (ranging from 3.6% to 10.3%),
      and seem to be even more prevalent in women, blacks, and the elderly. In the 3
      studies that examined isolated minor NSSTTA, the multivariable-adjusted hazard
      ratios for coronary mortality ranged from 1.24 to 1.66. Although gender, race,
      and age-specific differences in the prognostic significance of minor NSSTTA are
      not clear because of limited data, minor NSSTTA in asymptomatic patients are an
      important risk factor for coronary and cardiovascular mortality, independent of
      traditional risk factors. Minor NSSTTA are prevalent in asymptomatic individuals,
      and they confer increased risk for CVD and coronary heart disease (CHD),
      independent of traditional risk factors. Future studies with standardized
      methodology are needed to elucidate the physiological significance of minor
      NSSTTA and to further describe gender, race, and age-related differences in the
      prevalence and prognostic significance of minor NSSTTA.

PMID- 17438380
TI  - Pulmonary artery hypertension: caveolin-1 and eNOS interrelationship: a new
      perspective.
AB  - Pulmonary artery hypertension (PAH) is a sequela of a number of disparate
      diseases, often with a fatal consequence. Endothelial dysfunction is considered
      to be an early event during the development of PAH. Impaired availability of
      bioactive nitric oxide (NO) is a key underlying feature in most forms of clinical
      and experimental PAH. NO, generated by catalytic activity of endothelial NO
      synthase (eNOS) on l-arginine, modulates vascular function and structure. For
      optimal activation, eNOS is targeted to caveolae, the flask-shaped invaginations
      found on the surface of plasmalemmal membrane of a variety of cells, including
      endothelial cells. Caveolin-1, the major coat protein of caveolae, regulates eNOS
      activity. Evidence is accumulating to suggest that caveolin-1 may play a
      significant role in the pathogenesis of PAH. This review is intended to summarize
      recent findings indicating a role for caveolin-1 and caveolin-1/eNOS
      interrelationship in PAH.

PMID- 17438381
TI  - Transient apical ballooning: sheep in wolves' garb.
AB  - Takotsubo cardiomyopathy is a unique acute cardiac syndrome characterized by
      typical ischemic chest symptoms, an elevated ST segment on the electrocardiogram,
      and elevated cardiac disease markers. It is often misdiagnosed as acute
      myocardial infarction. Coronary angiography usually shows no evidence of
      obstructive atherosclerotic coronary artery disease. Left ventriculography and
      echocardiography reveal a peculiar regional systolic dysfunction with akinesis of
      the midventricle and apex and compensatory hyperkinesis of the basal ventricular
      segments. This syndrome has been shown to have a distinct temporal relationship
      with intense emotional stressors, and is characterized by an excellent clinical
      recovery when appropriate conservative measures are taken during the acute phase
      of the illness. In this review, we highlight the proposed pathophysiology and
      clinical manifestations of this recognized reversible form of myocardial failure.

PMID- 17438382
TI  - Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial
      agonist approved for smoking cessation.
AB  - Tobacco smoking remains a significant health problem in the United States. It has
      been associated with staggering morbidity and mortality, specifically due to
      malignancies and cardiovascular disease. Smoking cessation can be difficult and
      frequently requires pharmacologic interventions in addition to nonpharmacologic
      measures. Previously available agents are nicotine replacement products and
      bupropion, which increased quit rates by about 2-fold compared with placebo.
      Varenicline is the first drug in a new class known as the selective alpha4beta2
      nicotinic receptor partial agonists. In several randomized, double-blind, 52-week
      clinical trials involving healthy chronic smokers, varenicline demonstrated
      superiority to placebo and bupropion in terms of efficacy measures. Additionally,
      it improved tobacco withdrawal symptoms and reinforcing effects of smoking in
      relapsed patients. Patients should start therapy in combination with tobacco
      cessation counseling 1 week before quit date and continue the regimen for 12
      weeks. The dose of varenicline should be titrated to minimize nausea. The
      recommended dosage is 0.5 mg once daily (QD) on days 1-3; titrate to 0.5 mg twice
      daily (BID) on days 4-7; and 1 mg BID starting on day 8. An additional 12-week
      maintenance therapy may be considered for those who achieve abstinence. The most
      common side effects are nausea (30%), insomnia (18%), headache (15%), abnormal
      dreams (13%), constipation (8%), and abdominal pain (7%). Overall, varenicline is
      a breakthrough in the management of tobacco addiction and has demonstrated good
      efficacy in motivated quitters. It also provides an option for smokers who cannot
      tolerate other pharmacologic interventions.

PMID- 17438383
TI  - Development of a novel, accurate, automated, rapid, high-throughput technique
      suitable for population-based carrier screening for Fragile X syndrome.
AB  - PURPOSE: To develop a high-throughput, automated, accurate method suitable for
      population-based carrier detection of fragile X syndrome. METHODS: We developed a
      new method called capillary Southern analysis that allows automated high
      throughput screening for expanded fragile X mental retardation 1 (FMR1) alleles.
      Initially samples are analyzed by a multiplex polymerase chain reaction that
      contains an internal control to establish gender. All females heterozygous for
      two normal alleles are reported as normal without further analysis. All females
      homozygous at the FMR1 locus (24% of all analysis) are then analyzed by capillary
      Southern analysis. Theoretically this method can detect expansion as high as 2000
      CGG repeats, although in our series the largest nonmosaic FMR1 present was 950
      CGG repeats. After assay development, we performed capillary Southern analysis on
      995 female and 557 male samples submitted for fragile X syndrome testing by
      polymerase chain reaction and Southern blot. RESULTS: The polymerase chain
      reaction/capillary Southern analysis technique identified 100% of six female
      premutation carriers, seven full mutation carrier females, one premutation male,
      and five affected males. There was only one discrepancy between analysis by
      polymerase chain reaction/Southern blot and analysis by polymerase chain
      reaction/capillary Southern analysis. A single female sample appeared to be
      heterozygous for a premutation allele by polymerase chain reaction/capillary
      Southern analysis but was negative by Southern blot. It is possible this patient
      is a mosaic for the premutation allele, but because samples were deidentified, we
      were unable to determine whether this was a true false positive. CONCLUSION: We
      have developed an automated, high-throughput technique capable of detecting
      carriers of fragile X syndrome with 100% sensitivity and at least 99.5%
      specificity. This should allow population-based carrier detection for the most
      commonly inherited form of mental retardation.

PMID- 17438384
TI  - Abdominal visceral findings in patients with Marfan syndrome.
AB  - PURPOSE: Marfan syndrome is an autosomal dominant disorder historically defined
      by well-characterized features in the cardiovascular, ocular, and skeletal
      systems. To date, there have been no reports concerning abdominal visceral
      findings in this disorder. The purpose of this study was to determine the
      prevalence of abdominal visceral findings in patients with Marfan syndrome.
      METHODS: Computed tomography or magnetic resonance studies of 69 patients with
      Marfan syndrome and an age- and sex-matched cohort of control subjects were
      reviewed. The presence of abdominal visceral findings was noted. Chi-square and
      Student t tests were used to determine significance of differences between the
      patient and control groups. This retrospective study was approved by the local
      institutional review board and determined to be exempt from Health Insurance
      Portability and Accountability Act reporting requirements. RESULTS: Renal cysts
      were present in 41 Marfan patients (59.4%) versus 21 control subjects (30.4%),
      P=0.001. The average number of renal cysts was greater in Marfan patients than
      controls (2.4 vs. 0.9, P=0.005). Hepatic cysts were present in 24 Marfan patients
      (34.8%) versus 12 control patients (17.3%), P=0.02. The average number of hepatic
      cysts was also greater in Marfan patients than controls (0.9 vs. 0.3, P=0.027).
      Cholelithiasis was present in 12 Marfan patients (18.1%) versus one control
      patient (1.5%), P<0.001. CONCLUSIONS: Marfan syndrome patients have liver and
      renal cysts more often, in increased number, and at an earlier age than controls,
      in addition to an increased prevalence of cholelithiasis. Further study will be
      needed to relate these findings to recent developments concerning the underlying
      molecular genetics of this disorder.

PMID- 17438385
TI  - Cognitive dysfunction in adults with Van der Woude syndrome.
AB  - PURPOSE: Van der Woude syndrome is an autosomal dominant disorder manifested in
      clefts of the lip and/or palate and lip pits. There is phenotypic and genotypic
      overlap between Van der Woude syndrome and isolated cleft of the lip and/or
      palate. Subjects with isolated cleft of the lip and/or palate have been shown to
      have cognitive dysfunction. Given the similarities between Van der Woude syndrome
      and isolated cleft of the lip and/or palate, the current study was designed to
      evaluate the pattern of cognitive function in adults with Van der Woude syndrome.
      METHODS: Fourteen adults with Van der Woude syndrome were compared with age- and
      gender-matched controls. A battery of cognitive tests was administered to
      determine general IQ as well as more specific cognitive performance measures.
      RESULTS: All subjects with Van der Woude syndrome showed deficits in performance
      on an executive function task. In addition, males with Van der Woude syndrome had
      significantly lower scores on intelligence measures and on a verbal fluency task
      compared with controls. CONCLUSION: The pattern of cognitive function in Van der
      Woude syndrome is very similar to that seen in isolated cleft of the lip and/or
      palate. In addition, the findings have a significant gender effect in which males
      are more severely affected than females. This pattern is common to other
      conditions with a neurodevelopmental etiology, supporting the notion that the
      cognitive deficits of Van der Woude syndrome and isolated cleft of the lip and/or
      palate are due to abnormal brain development.

PMID- 17438386
TI  - Association between IRF6 and nonsyndromic cleft lip with or without cleft palate
      in four populations.
AB  - PURPOSE: The interferon regulatory factor 6 (IRF6), the gene that causes van der
      Woude syndrome has been shown to be associated with nonsyndromic cleft lip with
      or without palate in several populations. This study aimed to confirm the
      contribution of IRF6 to cleft lip with or without palate risk in additional Asian
      populations. METHODS: A set of 13 single nucleotide polymorphisms was tested for
      association with cleft lip with or without palate in 77 European American, 146
      Taiwanese, 34 Singaporean, and 40 Korean case-parent trios using both the
      transmission disequilibrium test and conditional logistic regression models.
      RESULTS: Evidence of linkage and association was observed among all four
      populations; and two specific haplotypes [GC composed of rs2235373-rs2235371
      (p.V274I) and AAG of rs599021-rs2235373-rs595918] showed the most significant
      over- and undertransmission among Taiwanese cases (P=9x10(-6) and P=5x10(-6),
      respectively). The AGC/CGC diplotype composed of rs599021-rs2235373-rs2013162
      showed almost a 7-fold increase in risk among the Taiwanese sample (P<10(-3)).
      These results confirmed the contribution of this gene to susceptibility of oral
      clefts across different populations; however, the specific single nucleotide
      polymorphisms showing statistical significance differed among ethnic groups.
      CONCLUSION: The high-risk genotypes and diplotypes identified here may provide a
      better understanding of the etiological role of this gene in oral clefts and
      potential options for genetic counseling.

PMID- 17438387
TI  - Replication and refinement of linkage of posterior polymorphous corneal dystrophy
      to the posterior polymorphous corneal dystrophy 1 locus on chromosome 20.
AB  - PURPOSE: The study purpose was to identify the genetic basis of posterior
      polymorphous corneal dystrophy, an autosomal dominant disorder of the corneal
      endothelium that is associated with the development of corneal edema,
      necessitating corneal transplantation for visual rehabilitation. Glaucoma also
      develops in up to 40% of patients with posterior polymorphous corneal dystrophy.
      METHODS: Linkage analysis, using microsatellite markers previously used to
      demonstrate linkage of posterior polymorphous corneal dystrophy to the chromosome
      20 candidate region known as posterior polymorphous corneal dystrophy 1, was
      performed in 29 members of a family with posterior polymorphous corneal
      dystrophy. Thirty-four microsatellite markers were used to refine the posterior
      polymorphous corneal dystrophy 1 interval. TCF8, located on chromosome 10, was
      screened in an affected family member to exclude posterior polymorphous corneal
      dystrophy 3. RESULTS: Significant evidence of linkage to the posterior
      polymorphous corneal dystrophy 1 interval was obtained with both single-point and
      multipoint analyses. The largest single-point log odds ratio score obtained was
      4.38 (theta=0) at marker D20S471; within 4.7 Mbp (7.2 cM) of D20S471 eight
      markers provided single-point log odds ratio scores of greater than 3.00 and
      three markers provided single-point log odds ratio scores greater than 4.00. The
      largest multipoint log odds ratio score obtained was 4.83, found across the
      adjacent markers D20S844, D20S191, D20S484, and D20S111. The support interval for
      posterior polymorphous corneal dystrophy 1 in the family we report is
      approximately 13.5 Mbp (10 cM) long and lies between the markers D20S182 and
      D20S195. Eleven markers have multipoint log odds ratio scores greater than 4.0
      within this region. No coding region mutations were identified in TCF8 in an
      affected member of the family, effectively excluding posterior polymorphous
      corneal dystrophy 3. CONCLUSIONS: The originally described 19.8 cM posterior
      polymorphous corneal dystrophy 1 candidate disease interval has been refined to a
      10 cM interval between markers D20S182 and D20S195. A portion of this refined
      interval overlaps a more recently reported posterior polymorphous corneal
      dystrophy 1 interval, with only 20 known and predicted genes mapped to the 2.4 cM
      common interval.

PMID- 17438388
TI  - Characteristics and perspectives of families waiting to adopt a child with Down
      syndrome.
AB  - PURPOSE: The study's purpose was to obtain information on the characteristics and
      perspectives of families interested in adopting children with Down syndrome.
      METHODS: A questionnaire-based survey was administered to individuals and
      families on a waiting list to adopt children with Down syndrome. Information on
      (1) demographic, (2) family structure, (3) Down syndrome exposure, (4) Down
      syndrome knowledge, (5) reasons for considering adoption, (6) adoption process,
      and (7) perspective on raising children with Down syndrome was assessed. RESULTS:
      From 199 mailed surveys, there were 72 respondents (36.2%) of whom six had
      previously adopted a child with Down syndrome. Forty-eight percent learned of the
      possibility of adopting children with Down syndrome through the Internet, whereas
      only one respondent obtained this information from a medical professional. The
      primary reasons for considering adoption were that prospective adoptive families
      were equipped with the necessary resources and had previous positive experiences
      with individuals who have Down syndrome. CONCLUSIONS: Many families are eager to
      adopt children with Down syndrome. Interest in this option stems from having
      resources to care for these children and previous positive experiences with
      individuals with Down syndrome. Information regarding adoption was rarely
      obtained from health care providers. When counseling pregnant women diagnosed
      with a Down syndrome fetus, adoption should be discussed so that all options
      regarding pregnancy management may be explored.

PMID- 17438389
TI  - Copy number analysis of survival motor neuron genes by multiplex ligation
      dependent probe amplification.
AB  - PURPOSE: To determine the copy number of survival motor genes using multiplex
      ligation-dependent probe amplification. METHODS: Three hundred seventy-three
      subjects were recruited and divided into three groups. Group 1 included 310
      subjects without a history of muscular atrophy, Group 2 consisted of 18 patients
      and 45 carriers of spinal muscular atrophy, and Group 3 included 20 subjects who
      were previously tested with denatured high-performance liquid chromatography. The
      copy number of survival motor neuron 1 and survival motor neuron 2 genes was
      determined with a commercially available multiplex ligation-dependent probe
      amplification kit. RESULTS: Twenty-one genotypes of the survival motor neuron
      genes could be clearly defined in this series. The whole process of genotyping
      took <48 hours. In Group 1, 2:2 (survival motor neuron 1:survival motor neuron 2)
      was most common (52.90%), followed by 2:1 (30.32%); six (1.94%) subjects were
      found to be carriers of 1:2 or 1:3. In Group 2, all 18 patients had zero copies
      of the survival motor neuron 1 gene and variable copies of the survival motor
      neuron 2 gene. In Group 3, three subjects who had been told they were carriers of
      spinal muscular atrophy turned out to be noncarriers by multiplex ligation
      dependent probe amplification. All 51 carriers from Groups 1 and 2 had one copy
      of the survival motor neuron 1 gene and one to four copies of the survival motor
      neuron 2 gene. CONCLUSION: Multiplex ligation-dependent probe amplification is a
      simple and efficient method for copy number analysis of survival motor neuron
      genes. It can be used to detect the homozygous and heterozygous survival motor
      neuron deletion of spinal muscular atrophy.

PMID- 17438391
TI  - Joy, work, and health care management.

PMID- 17438390
TI  - Bax gene G(-248)A promoter polymorphism is associated with increased lifespan of
      the neutrophils of patients with osteomyelitis.
AB  - BACKGROUND: Patients with osteomyelitis have a decreased rate of spontaneous
      apoptosis of their peripheral blood neutrophils. The G(-248)A polymorphism in the
      promoter region of the bax gene is associated with prolonged peripheral blood
      neutrophil survival in leukemic patients and may play some role in osteomyelitis.
      METHODS: Bax G(-248)A promoter polymorphism was detected by DNA amplification
      using polymerase chain reaction, followed by restriction fragment length
      polymorphism analysis. Spontaneous apoptosis of peripheral blood neutrophils was
      measured by propidium iodide, annexin V, and flow cytometry, and Bax was
      quantified by Western blotting. RESULTS: The bax promoter polymorphism A allele
      was significantly more frequent in 80 patients with osteomyelitis than in 220
      healthy donors (18.1% vs. 10.6%, chi=4.84, odds ratio=1.81, 95% confidence
      interval=1.06-3.07, P=.028). Carriers of the A allele had a lower apoptotic rate
      of their peripheral blood neutrophils compared with noncarriers (33.3+/-16.7 vs.
      43.1+/-3.1, P=.036). Patients with the AA genotype showed a lower expression of
      the Bax protein compared with carriers of other genotypes (P=.038). CONCLUSIONS:
      Substitution of a nucleotide G-->A at position -248 in the bax gene was more
      frequent in patients with osteomyelitis and was associated with a longer lifespan
      of their peripheral blood neutrophils and lower Bax protein expression. These
      findings may play a role in the pathogenesis of osteomyelitis.

PMID- 17438392
TI  - Building customer capital through knowledge management processes in the health
      care context.
AB  - BACKGROUND: Customer capital is a value generated and an asset developed from
      customer relationships. Successfully managing these relationships is enhanced by
      knowledge management (KM) infrastructure that captures and transfers customer
      related knowledge. The execution of such a system relies on the vision and
      determination of the top management team (TMT). The health care industry in
      today's knowledge economy encounters similar challenges of consumerism as its
      business sector. Developing customer capital is critical for hospitals to remain
      competitive in the market. PURPOSES: This study aims to provide taxonomy for
      cultivating market-based organizational learning that leads to building of
      customer capital and attaining desirable financial performance in health care.
      With the advancement of technology, the KM system plays an important moderating
      role in the entire process. METHODOLOGY/APPROACH: The customer capital issue has
      not been fully explored either in the business or the health care industry. The
      exploratory nature of such a pursuit calls for a qualitative approach. This study
      examines the proposed taxonomy with the case hospital. The lessons learned also
      are reflected with three US-based health networks. FINDINGS: The TMT incorporated
      the knowledge process of conceptualization and transformation in their
      organizational mission. The market-oriented learning approach promoted by TMT
      helps with the accumulation and sharing of knowledge that prepares the hospital
      for the dynamics in the marketplace. Their key knowledge advancement relies on
      both the professional arena and the feedback of customers. The
      institutionalization of the KM system and organizational culture expands the
      hospital's customer capital. PRACTICE IMPLICATIONS: The implication is twofold:
      (1) the TMT is imperative for the success of building customer capital through KM
      process; and (2) the team effort should be enhanced with a learning culture and
      sharing spirit, in particular, active nurse participation in decision making and
      frontline staff's role in providing a delightfully surprising patient experience.

PMID- 17438393
TI  - The effect of payer mix on the adoption of information technologies by hospitals.
AB  - BACKGROUND: Numerous studies have examined the relationship between organization
      characteristics and hospital adoption of information technology (IT). However, no
      known study has examined whether patient characteristics of those treated at a
      given hospital influences the decision to adopt IT. PURPOSE: The present study
      combines primary and secondary data to examine the effect of payer mix (the
      combination of payers that make up a given hospital's patient discharges) on IT
      adoption in hospitals. METHODS: Survey data from Florida hospitals were combined
      with the state's hospital discharge database. Multiple regression analyses were
      used to analyze the data. RESULTS: When examining Medicare, Medicaid, traditional
      commercial insurance, and managed-care plans, only an increase of managed-care
      patients, as a percentage of hospital discharges, was associated with a
      significant increased likelihood to adopt clinical and administrative IT
      applications by hospitals. PRACTICE IMPLICATIONS: Our results suggest that
      increasing cost pressures associated with managed-care environments are driving
      hospitals' adoption of clinical and administrative IT systems as such adoption is
      expected to improve hospital efficiency and lower costs. Given that such cost
      pressures are also emergent in Medicare, Medicaid, and traditional third-party
      payment environments, an opportunity exists for these parties to motivate
      hospital IT adoption as a means for cost reduction.

PMID- 17438394
TI  - The influence of payer mix on electronic health record adoption by physicians.
AB  - BACKGROUND: Numerous studies have examined the relationship between physician
      practice characteristics and electronic health record (EHR) adoption. Little is
      known about how payer mix influences physicians' decisions to implement EHR
      systems. PURPOSE: This study examines how different proportions of Medicare,
      Medicaid, and privately insured patients in physicians' practices influence EHR
      adoption. METHODOLOGY: Data from a large-scale survey of physician's use of
      information technologies in Florida were analyzed. Physicians were categorized
      based on their responses to questions regarding the proportion of patients in
      their practice that use Medicare, Medicaid, or private insurance products. The
      binary dependent variable of interest was EHR adoption among physicians. Adjusted
      odds ratios (ORs) were computed using logistic regression modeling techniques.
      The model examined the effect of changes in each payer type on EHR adoption,
      controlling for various practice characteristics. FINDINGS: Physicians with the
      highest percentage of Medicaid patients in their practices were significantly
      less likely to indicate using an EHR system when compared with those in the low
      volume Medicaid group (OR = 0.690; 95% confidence interval [CI] = 0.50-0.95). No
      differences in EHR adoption were detected among physicians in the low, median,
      and high Medicare volume classifications. Among the private payer
      classifications, physicians whose practices were in the median group indicated
      significantly greater EHR use than those with relatively low levels of privately
      insured patients (OR = 1.62; 95% CI = 1.16-2.27). Those in the high-volume
      private payer group were also more likely than the low-volume group to have an
      EHR system, but this trend did not reach statistical significance (OR = 1.44; 95%
      CI = 0.96-2.16). PRACTICE IMPLICATIONS: Governmental insurance programs are
      either not influencing or negatively influencing EHR adoption among physicians in
      Florida. Given the quality and cost benefits associated with EHR use
      (particularly for health care payers), policymakers should consider strategies to
      incentivize or reward EHR adoption among doctors who care for Medicare and
      Medicaid patients.

PMID- 17438395
TI  - Predictors of registered nurses' organizational commitment and intent to stay.
AB  - BACKGROUND: Health care reform has significantly altered employment relations.
      Research findings suggest that the presence or absence of supportive work
      environments helps explain the differences observed in employee attitudes and
      turnover intentions. PURPOSES: The purposes of this study were to examine
      frontline registered nurses' (RNs') perceptions of organizational culture and
      attitudes and behaviors and test a model linking culture to outcome
      (organizational commitment and intent to stay). METHODOLOGY: A non-experimental
      predictive survey design was used to test the model in a sample (N = 343) of
      acute care RNs employed in one Canadian province. Data were collected with the
      following scales: Emotional Climate, Practice Issues, Collaborative Relations,
      Psychological Contract Violation, General Job Satisfaction, Organizational
      Commitment Questionnaire, and Intent to Stay. FINDINGS: The response rate was
      29.4%. Most respondents were middle aged and diploma prepared, were in their
      current positions for 5 years or more, had 10 or more years of nursing
      experience, and worked full time. Despite moderate levels of job satisfaction,
      RNs held negative perceptions of culture (emotional climate, practice-related
      issues, and collaborative relations), trust, and commitment and were unlikely to
      stay with current employers. Structural equation modeling provided support for
      the impact of culture, trust, and satisfaction on commitment and partial support
      for intent to stay, explaining 45 and 31% of the variance, respectively. PRACTICE
      IMPLICATIONS: The development and implementation of policies and interventions
      aimed at creating more supportive work environments and greater trust in
      employers and job satisfaction have merit. The most obvious benefit from such
      strategic interventions is the potential for improving RNs' organizational
      commitment and reducing turnover intentions.

PMID- 17438396
TI  - Relationship between management philosophy and clinical outcomes.
AB  - BACKGROUND: Medical research continues to focus overwhelmingly on biomedical
      interventions, such as drugs, devices, and procedures. The dysfunctional health
      care cultures and systems need more attention for quality of care to improve
      further. PURPOSE: The existing health services management research has not used a
      systematic theoretical framework to predict the effects of organizational
      variables on clinical outcomes. This study tests the theoretical model proposed
      by N. Khatri, A. Baveja, S. Boren, and A. Mammo (2006). METHODOLOGY: This study
      surveyed employees from hospitals in Missouri. The sample consisted of 77
      respondents from 16 hospitals. FINDINGS: The control-based management approach
      (Management Control and Silos) was found to be positively associated with Culture
      of Blame and negatively with Learning From Mistakes. In contrast, the commitment
      based approach (Fair Management Practices and Employee Participation) was
      negatively associated with Culture of Blame and positively with Learning From
      Mistakes, Camaraderie, and Motivation. Mediating variables of Learning From
      Mistakes and Camaraderie showed a significant negative relationship with Medical
      Errors. Learning From Mistakes, Camaraderie, and Motivation all showed a
      significant positive relationship with Quality of Patient Care. The mediating
      variables had much stronger relationships with Medical Errors and Quality of
      Patient Care than did the independent variables, lending support to the proposed
      mediation. IMPLICATIONS FOR PRACTICE: Health care organizations can improve the
      quality of care and reduce medical errors significantly by enhancing learning
      from mistakes and boosting camaraderie and morale of their employees. They can do
      so by breaking down silos in their structures, implementing just and fair
      management practices, and involving employees in decision making.

PMID- 17438397
TI  - Coordination between formal providers and informal caregivers.
AB  - BACKGROUND: The increased "outsourcing" of care-related tasks to patients and
      their informal caregivers is part of a broader trend in service industries toward
      engaging customers as "coproducers" of service outcomes. As both quasi-patients
      and quasi-providers, caregivers may play a critical role in successful
      coproduction, but they require coordination with care providers to play this role
      effectively. When tasks are highly interdependent, uncertain, and time
      constrained, as they often are in health care, relational forms of coordination
      are expected to be most effective. PURPOSES: This study explores the effects of
      coordination between formal providers and informal caregivers on caregiver
      preparation to provide care at home and the effect of caregiver preparation on
      patient outcomes. Gittell's theory of relational coordination posits that
      effective coordination occurs through frequent, high-quality communication that
      is supported by relationships of shared goals, shared knowledge, and mutual
      respect. We extend the relational coordination model, previously used to examine
      coordination between formal providers, to encompass coordination of care between
      formal providers and informal caregivers. METHODOLOGY: We surveyed patients
      before and 12 weeks after knee replacement surgery to assess outcomes. At 6 weeks
      postsurgery, we surveyed their caregivers regarding coordination with providers
      and preparation to provide care. FINDINGS: We found that relational coordination
      between formal providers and caregivers improves caregiver preparation to provide
      care, which, in turn, is positively associated with patients' freedom from pain,
      functional status, and mental health. IMPLICATIONS: Providers should be
      encouraged to attend to the interpersonal aspects of their interactions with
      caregivers to promote relational coordination, which may ultimately benefit the
      patient's health. It is not enough, however, to urge providers to build shared
      goals, shared knowledge, and mutual respect with patients and caregivers.
      Dedicated resources and support are needed, given the context of constrained
      resources and brief encounters in which providers deliver care.

PMID- 17438398
TI  - Increasing the relevance of research to health care managers: hospital CEO
      imperatives for improving quality and lowering costs.
AB  - BACKGROUND: Evidence-based management assumes that available research evidence is
      consistent with the problems and decision-making conditions faced by those who
      will utilize this evidence in practice. PURPOSE: This article attempts to
      identify how hospital leaders view key determinants of hospital quality and
      costs, as well as the fundamental ways these leaders "think" about solutions to
      quality and cost issues in their organizations. The objective of this analysis is
      to better inform the research agenda and approaches pursued by health services
      research so that this research reflects the "realities" of practice in hospitals.
      METHODS: We conducted a series of semistructured interviews with a convenience
      sample of eight hospital and three health system leaders. Questions focused on
      current and future challenges facing hospitals as they relate to hospital
      quality, costs, and efficiency, and potential solutions to those challenges.
      FINDINGS: Nine major organizational and managerial factors emerged from the
      interviews, including staffing, evidence-based practice, information technology,
      data availability and benchmarking, and leadership. Hospital leaders tend to
      think about these factors systemically and consider process-related factors as
      the important drivers of cost and quality. PRACTICE IMPLICATIONS: The results
      suggest a need to expand the methods utilized by health services researchers to
      make their research more relevant to health care managers. Expanding research
      methods to reflect the systemic way that managers view the challenges and
      solutions facing their organizations may enhance the application of research
      findings into management practice. Finally, better communication is needed
      between the research and practice communities. Researchers must learn to think
      more like managers if their research is to be relevant, and managers must learn
      to more effectively communicate their issues with the research community and
      frame their problems in researchable terms.

PMID- 17438399
TI  - Nurses' intent to leave the profession: issues related to gender, ethnicity, and
      educational level.
AB  - BACKGROUND: The increase in demand for registered nurses will exceed supply by
      29% by 2020, which is due in part to difficulties in retaining the existing
      nursing workforce. The researchers postulated that nursing professionals are
      experiencing a higher level of job dissatisfiers than motivators, and this is
      causing a high percentage of nurses to consider leaving the profession. Prior
      research has found that nurses' dissatisfaction with their working environments
      is a predictor of their intent to leave their professions; however, few have
      addressed the demographic characteristics of the population as predictors of this
      intent. PURPOSE: The purpose of this study was to explore issues relating to the
      retention of the existing nursing workforce. This article describes the results
      of a research study that was designed to identify and evaluate the variables that
      contribute to nurses' intent to leave their profession and the relationships of
      gender, ethnicity, and educational levels to this intent. METHODOLOGY: Data were
      collected from 284 nurses, of which 46% indicated that they were considering
      leaving their profession. Using multiple regression analysis, the researchers
      were able to test whether certain groups (according to gender, ethnicity, and
      education levels) had a greater intent to leave the profession and what factors
      were related to each subgroups' intent to leave. FINDINGS: The results of this
      study revealed that (a) nurses who are male, are White-non-Hispanic, or have less
      than a master's degree are more inclined to consider leaving the nursing
      profession, and (b) benefits were a more important consideration to male and
      White-non-Hispanic nurses regarding their intent to leave the nursing profession.
      PRACTICE IMPLICATIONS: In today's environment of low reimbursement and high cost
      containment, health care managers need to focus on those items that will have the
      greatest impact on retaining high-quality nurses because nurses "make the
      critical, cost-effective difference in providing safe, high-quality patient
      care."

PMID- 17438400
TI  - Do corporate chains affect quality of care in nursing homes? The role of
      corporate standardization.
AB  - BACKGROUND: Chain-owned nursing homes have become the predominant type of
      provider in the United States, but little is known about their management
      structures. Prior research has found that chain ownership has significant effects
      on health outcomes, but why that is the case is not well understood. PURPOSE:
      This study examines the effects of corporate-mandated standardization and
      corporate-sponsored training in administrative and clinical processes on the
      total number of deficiencies reported for a facility and on the percentage of
      residents with pressure ulcers for chain-owned facilities in Michigan and North
      Carolina. METHODOLOGY: Data on the corporate practices of standardization and
      training were collected in a mail survey of facility administrators in Michigan
      in 2001 and North Carolina in 2002. We received responses from 117 of 239 chain
      owned facilities in Michigan and 86 of 270 in North Carolina. Survey responses
      were merged with facility characteristics taken from the On-line Survey,
      Certification, and Report System. Seemingly unrelated regression was used to
      estimate the effects of standardization on the count of health deficiencies and
      percentage of residents with pressure ulcers simultaneously. FINDINGS: Health
      deficiencies, but not pressure ulcers, were lower in facilities of chains with
      greater overall corporate standardization. More detailed analysis revealed that
      standardization of facilities' physical plant lowered both deficiencies and
      pressure ulcers and standardization of clinical activities lowered pressure
      ulcers (but not deficiencies). In contrast, standardization of administrative
      practices increased pressure ulcers (but not deficiencies). PRACTICE
      IMPLICATIONS: Corporate standardization of resident-centered activities such as
      clinical guidelines and common facility layouts may contribute to superior
      resident care, whereas primary reliance on administrative standardization may
      interfere with residents' needs. Chains need to balance administrative efficiency
      with the local needs of individual chain-owned facilities and their residents.

PMID- 17438401
TI  - A comparative analysis of the community contributions and profits of Virginia's
      hospitals.
AB  - BACKGROUND: In return for receiving favorable treatment from the government, U.S.
      general hospitals are expected to provide contributions to their community
      consisting of charity care, bad debt, and taxes paid. Recently, the Government
      Accountability Office proposed that an analysis that compares what for-profit and
      nonprofit hospitals contribute be conducted. PURPOSE: For 72 Virginia hospitals,
      it is determined whether (a) for-profit hospitals' community contributions exceed
      their profits and (b) nonprofit hospitals' community contributions exceed the for
      profits' contributions in addition to the nonprofits' forgone taxes.
      METHODOLOGY/APPROACH: Based on audited fiscal year 2004 financial statements, six
      null hypotheses were tested for significant differences between the two
      independent variables, namely, hospital charter and size, and the three dependent
      variables, including (a) operating income, (b) the ratio of community
      contributions to net patient revenues, and (c) the ratio of community
      contributions to operating income. FINDINGS: No significant differences were
      found to exist between (a) hospital charter and operating income, (b) hospital
      charter and the percentage of community contributions to net patient revenues,
      and (c) hospital charter and the percentage of community contributions to
      operating income. The community contributions of nonprofits exceeded their taxes
      forgone by a wide margin, but they fell short of exceeding the for-profits'
      community contributions plus the taxes forgone by a very slight margin. PRACTICE
      IMPLICATIONS: Hospital management, in conjunction with health care policy
      planners, needs to develop mutually acceptable standards regarding the required
      level of hospitals' community contributions. It is proposed that the most
      equitable standard is "quartile comparisons" for a given hospital's financial
      performance and its level of community contributions. Furthermore, to reduce
      charity care, it is imperative that high-cost hospital treatment of primary
      health care for indigent patients be shifted to lower cost delivery systems.

PMID- 17438402
TI  - In vivo endothelial denudation disrupts smooth muscle caveolae and differentially
      impairs agonist-induced constriction in small arteries.
AB  - Experiments were performed to determine the effects of endothelial denudation in
      vivo on vasoconstrictor responses of mouse tail artery segments in vitro. A
      sterile wire (70 microm diameter) was inserted into tail arteries of anesthetized
      mice to mechanically denude the endothelium, and the animals were allowed to
      recover for 48 hours. The function of pressurized tail artery segments was then
      studied in vitro. Intimal injury markedly reduced endothelium-dependent
      relaxation to acetylcholine. Constriction evoked by the selective alpha1
      adrenoceptor (alpha1-AR) agonist, phenylephrine, was not affected by in vivo
      endothelial denudation, indicating that the contractile function of vascular
      smooth muscle cells (VSMCs) was not impaired. However, constriction to the
      selective alpha2-AR agonist UK14304 or to endothelin-1 was significantly
      inhibited. Confocal microscopy of intact tail arteries localized caveolin-1 to
      punctuate structures, arranged in rows on or close to the surface of VSMCs. After
      in vivo endothelial denudation, this pattern was disrupted and caveolin-1 was
      localized to intracellular sites. When VSMC caveolae were disrupted in control
      arteries using the cholesterol acceptor methyl-beta-cyclodextrin, there was a
      similar impairment in constriction to endothelin-1 or alpha2-AR stimulation, but
      not alpha1-AR activation. These results suggest that intimal injury to small
      cutaneous arteries disrupts VSMC surface caveolae and selectively impairs
      constriction to stimuli that are dependent on these structures for signaling.

PMID- 17438403
TI  - Carvedilol reduces elevated B-type natriuretic peptide in dialyzed patients
      without heart failure: cardioprotective effect of the beta-blocker.
AB  - Elevated plasma B-type natriuretic peptide (BNP) predicts future cardiovascular
      events in dialyzed patients without heart failure. We investigated whether
      carvedilol reduces the elevated BNP in these patients. Asymptomatic patients on
      chronic hemodialysis with elevated BNP but without clinical signs of heart
      failure were randomly assigned to receive either carvedilol (n = 10) or nothing
      (control group, n = 10). BNP and malondialdehyde-low density lipoprotein (MDA
      LDL) were measured, and ultrasound cardiography was performed at baseline and at
      3 months. Carvedilol reduced the concentrations of BNP (551 +/- 90 to 237 +/- 174
      ng/L, P < 0.01) and MDA-LDL (174 +/- 63 to 85 +/- 23 U/L, P < 0.01) and increased
      the velocity ratio of E to A waves of the transmitral flow (E/A: 0.59 +/- 0.04 to
      0.71 +/- 0.05, P < 0.05), while no such alterations were observed in the control
      group. The reduction in BNP concentration was correlated with that in MAD-LDL and
      the increase in the E/A. There was a significant correlation between the increase
      in the E/A and the reduction in MDA-LDL concentration. Thus, carvedilol reduces
      the elevated BNP by improving left ventricular diastolic function in dialyzed
      patients without heart failure, which may be attributable to the antioxidant
      property of the beta-blocker. Administering carvedilol may improve the prognosis
      in this population.

PMID- 17438404
TI  - In vitro and in vivo effects of the atrial selective antiarrhythmic compound
      AVE1231.
AB  - The novel compound AVE1231 was investigated in order to elucidate its potential
      against atrial fibrillation. In CHO cells, the current generated by hKv1.5 or
      hKv4.3 + KChIP2.2b channels was blocked with IC50 values of 3.6 microM and 5.9
      microM, respectively. In pig left atrial myocytes, a voltage-dependent outward
      current was blocked with an IC50 of 1.1 microM, mainly by accelerating the time
      constant of decay. Carbachol-activated IKACh was blocked by AVE1231 with an IC50
      of 8.4 microM. Other ionic currents, like the IKr, IKs, IKATP, ICa, and INa were
      only mildly affected by 10 microM AVE1231. In guinea pig papillary muscle the
      APD90 and the upstroke velocity were not significantly altered by 30 microM
      AVE1231. In anesthetized pigs, oral doses of 0.3, 1, and 3 mg/kg AVE1231 caused a
      dose-dependent increase in left atrial refractoriness (LAERP), associated by
      inhibition of left atrial vulnerability to arrhythmia. There were no effects on
      the ECG intervals, ventricular monophasic action potentials, or ventricular
      refractory periods at 3 mg/kg AVE1231 applied intravenously. In conscious goats,
      both AVE1231 (3 mg/kg/h iv) and dofetilide (10 microg/kg/h iv) significantly
      prolonged LAERP. After 72 hours of tachypacing, when LAERP was shortened
      significantly (electrical remodelling), the prolongation of LAERP induced by
      AVE1231 was even more pronounced than in sinus rhythm. In contrast, the effect of
      dofetilide was strongly decreased. The present data demonstrate that AVE1231
      blocks early atrial K channels and prolongs atrial refractoriness with no effects
      on ECG intervals and ventricular repolarisation, suggesting that it is suited for
      the prevention of atrial fibrillation in patients.

PMID- 17438405
TI  - Vasorelaxant effects of icariin on isolated canine coronary artery.
AB  - Owing to its cardiovascular therapeutical effects, icariin, a flavonoid isolated
      from Epimedii herba, is considered to be the major active constituent of Epimedii
      herba. The aim of this study is to investigate the effect of icariin on
      precontracted coronary artery isolated from canine. Coronary artery segments were
      isolated from normal anesthetized Beagle dogs and cut into 5-mm rings. The rings
      were mounted in an organ chamber and contracted by either 40 mM KCl or 10 microM
      PGF2alpha, and vasorelaxant tone to icariin was measured. Treatment of icariin
      could significantly produce a relaxation of precontracted coronary arterial rings
      with intact endothelium in a concentration-dependent manner. Comparatively, the
      vasorelaxation disappeared in denuded-endothelium rings. Furthermore, the
      vasorelaxant effect of icariin was blocked by Nomega-Nitro- L-arginine Methyl
      Ester (L-NAME), 1H-[1, 2, 4]-oxadiazolo [4, 3-a] quinoxalin-1-one (ODQ) but not
      by indomethacin and glibenclamide, respectively. Tetraethylammonium (TEA) could
      partly antagonize the vasorelaxant effect triggered by icariin. There was no
      significant gene expression difference of the endothelial nitric oxide synthase
      (eNOS) gene in coronary arterial rings among the different concentrations of
      icariin by RT-PCR, but the activity of eNOS was increased in a concentration
      dependent manner after icariin exposure. These results suggest that icariin
      produces NO-dependent relaxation in the isolated canine coronary artery, and the
      possible mechanism is involved in the activation of eNOS protein and NO-cGMP
      pathway.

PMID- 17438406
TI  - Cardioprotective properties of humoral factors released from rat hearts subject
      to ischemic preconditioning.
AB  - Myocardial protection can be achieved by transfer of coronary effluent from
      ischemically preconditioned to non-preconditioned hearts. This study was designed
      to test the hypothesis that preconditioned effluent from rat hearts purified by
      Sep-Pak C-18 cartridges could induce remote cardioprotection against
      ischemia/reperfusion (I/R) injury through the activation of protein kinase C
      signaling pathway. Buffer-perfused rat hearts were subject to 30 min ischemia and
      60 min reperfusion. The myocardial I/R injury was assessed by postischemic
      contractile function recovery and infarct size. The protective effect of coronary
      effluent collected during ischemic preconditioning (IPC) was tested in non
      preconditioned hearts in presence or absence of a PKC inhibitor, chelerythrine.
      Infarct size was 17 +/- 2% in preconditioned versus 37 +/- 1% in control hearts
      (P < 0.001). Hearts perfused with fresh preconditioned effluent had infarct sizes
      of 16 +/- 3% versus 36 +/- 1% in hearts treated with non-preconditioned effluent.
      The cardioprotective effect was lost when the effluent was left at room
      temperature during 24 h (infarct size, 40 +/- 3%) or heated to 70 degrees C (26
      +/- 4%, P < 0.05) or 100 degrees C (39 +/- 1%, P < 0.001). The lyophilized
      effluent was stable for 30 days, and its purification in a Sep-Pak C-18 column
      resulted in a hydrophobic fraction that reduced the infarct size to 17 +/- 2%
      versus 38 +/- 2% for the hydrophilic fraction. Chelerythrine (100 microM)
      inhibited the reduction of infarct size induced by IPC (35 +/- 4%) or hydrophobic
      fraction (37 +/- 3%). Recovery of the contractile function at reperfusion was
      higher in preconditioned group (74 +/- 6% versus 17 +/- 7% in control, P < 0.001)
      and hydrophobic fraction (66 +/- 7% versus 8 +/- 4% in hydrophilic fraction, P <
      0.001). Similarly, chelerythrine was able to abrogate the contractile function
      recovery (12 +/- 6%, P < 0.001 versus preconditioned group and 19 +/- 7%, P <
      0.001 versus hydrophobic fraction). In conclusion, the cardioprotective factors
      released in the coronary effluent by IPC are thermolabile hydrophobic substances
      with molecular weights higher than 3.5 kDa and acting through PKC activation.

PMID- 17438407
TI  - Sarpogrelate hydrochloride, a selective 5-HT2A antagonist, improves vascular
      function in patients with peripheral arterial disease.
AB  - Peripheral arterial disease (PAD) is 1 of the major manifestations of
      atherosclerosis. PAD is associated with endothelial dysfunction. Sarpogrelate
      hydrochloride, a selective 5-HT2A antagonist, has been widely used as an anti
      platelet agent for the treatment of PAD. There is no information on whether
      endothelial function is improved after initiation of sarpogrelate treatment in
      patients with PAD. The purpose of this study was to evaluate the effects of
      sarpogrelate on endothelial function in patients with PAD. We divided PAD
      patients into 2 groups: those treated with sarpogrelate at a dose of 100 mg 3
      times per day orally for 12 weeks (sarpogrelate group, n = 10), and those who
      remained on conventional therapy (control group, n = 11). Forearm blood flow
      (FBF) and leg blood flow (LBF) responses to reactive hyperemia (RH) and
      sublingual administration of nitroglycerin (NTG) were measured using strain-gauge
      plethysmography. After 12 weeks of sarpogrelate administration, FBF and LBF
      responses during RH showed significant increases from 13.2 +/- 1.7 to 18.1 +/-
      2.2 mL/min per 100 mL tissue (P < 0.01) and from 8.2 +/- 0.9 to 14.2 +/- 2.1
      mL/min per 100 mL tissue (P < 0.05), respectively. Sarpogrelate-induced
      augmentation of FBF and LBF responses to RH was maintained at 24 weeks. No change
      was observed in the control group at each follow-up time point. The changes in
      FBF and LBF after sublingual NTG were similar during follow-up periods in the 2
      groups. These findings suggest that long-term oral administration of sarpogrelate
      improves vascular function in patients with PAD.

PMID- 17438408
TI  - Zotarolimus, a novel sirolimus analogue with potent anti-proliferative activity
      on coronary smooth muscle cells and reduced potential for systemic
      immunosuppression.
AB  - Sirolimus (rapamycin) is an immunosuppressant used in preventing allograft
      rejection and in drug-eluting stents to prevent restenosis after angioplasty.
      Zotarolimus, an analogue of sirolimus, was designed to have a shorter in vivo
      half-life. Zotarolimus was found to be mechanistically similar to sirolimus in
      having high-affinity binding to the immunophilin FKBP12 and comparable potency
      for inhibiting in vitro proliferation of both human and rat T cells. Rat
      pharmacokinetic studies with intravenous dosing demonstrated terminal elimination
      half-lives of 9.4 hours and 14.0 hours for zotarolimus and sirolimus,
      respectively. Given orally, T1/2 values were 7.9 hours and 33.4 hours,
      respectively. Consistent with its shorter duration, zotarolimus showed a
      corresponding and statistically significant 4-fold reduction in potency for
      systemic immunosuppression in 3 rat disease models. Pharmacokinetic studies in
      cynomolgus monkey underpredicted the half-life difference between zotarolimus and
      sirolimus apparent from recent clinical data. In vitro inhibition of human
      coronary artery smooth muscle cell proliferation by zotarolimus was comparable to
      sirolimus. Drug-eluting stents for local delivery of zotarolimus to the vessel
      wall of coronary arteries are in clinical development. The pharmacological
      profile of zotarolimus suggests it may be advantageous for preventing restenosis
      with a reduced potential for causing systemic immunosuppression or other side
      effects.

PMID- 17438409
TI  - In vivo cardiac electrophysiologic and antiarrhythmic effects of an isoquinoline
      IKur blocker, ISQ-1, in rat, dog, and nonhuman primate.
AB  - The cardiac electrophysiologic effects of ISQ-1, an isoquinolinone I(Kur)
      blocker, were characterized in vivo. In rat, ISQ-1 elicited maximal 33% to 36%
      increases in atrial and ventricular refractoriness at a plasma concentration of
      11.5 microM. In African green monkey, ISQ-1 increased atrial refractory period
      (maximal 17% at plasma concentration up to 20 microM) with no effect on
      ventricular refractory period or ECG QTc. Likewise in dog, ISQ-1 increased atrial
      refractory period (maximal 16% at plasma concentration up to 2 microM) with no
      effect on ventricular refractory period or QTc. In contrast, studies with
      ibutilide in nonhuman primate and dog demonstrated concomitant increases in
      atrial and ventricular refractoriness and QTc. Additionally, in a dog model of
      atrial flutter, ISQ-1 terminated ongoing flutter at doses (2.5 +/- 0.5 mg/kg IV)
      that selectively prolonged atrial refractoriness (13% increase), whereas flutter
      termination with ibutilide occurred at doses that increased both atrial and
      ventricular refractoriness as well as QTc. Of note, the cardiac
      electrophysiologic profiles displayed by ISQ-1 in these species were similar to
      those reported previously by our lab with a structurally distinct I(Kur) blocker.
      Taken together, these results further support the inhibition of I(Kur) as an
      approach to terminate atrial arrhythmia.

PMID- 17438410
TI  - Oxidation of low-density lipoprotein cholesterol following administration of
      poloxamer 407 to mice results from an indirect effect.
AB  - Atherosclerosis is an inflammatory response to accumulation of cholesterol in the
      artery wall. Low-density lipoproteins (LDL) accumulate and are oxidized to
      proinflammatory compounds in the arterial intima during hypercholesterolemia,
      leading to activation of endothelial cells, macrophages, and T cells. We sought
      to define the role of oxidized LDL (oxLDL) in the poloxamer 407 (P-407)-induced
      mouse model of dose-dependent hyperlipidemia and atherosclerosis developed in our
      laboratory. The hyperlipidemic agent P-407 was evaluated for its ability to
      oxidize native LDL in vitro as determined by measuring the rate of formation of
      conjugated dienes, as well as malondialdehyde (MDA) production using the
      thiobarbituric acid reactive substances assay. Additionally, plasma obtained from
      C57BL/6 mice treated with P-407 for 100 days and maintained on either a normal
      diet or a diet supplemented with 0.5% w/w cholic acid was assayed for both MDA
      and lipid hydroperoxide content. Lastly, plasma from these same groups of mice
      was analyzed for the presence of immunoglobulin (Ig) G and IgM autoantibodies
      against oxLDL. Our results indicate that P-407 is unable to directly oxidize
      native LDL in vitro. However, plasma obtained from P-407-treated mice
      demonstrated a significant (P < 0.05) increase in the content of oxidized lipids,
      but showed a significant (P < 0.05) decrease in the concentration of lipid
      hydroperoxides when compared to controls. Both plasma IgG and IgM antibodies to
      MDA-modified LDL (MDA-LDL) were significantly (P < 0.05) elevated in P-407
      treated mice, as was IgG1 anti-MDA-LDL, whereas the titer of IgG2a anti-MDA-LDL
      was significantly (P < 0.05) reduced. We suggest that P-407 causes oxidation of
      LDL in vivo by an indirect mechanism and we further conclude that P-407-induced
      hypercholesterolemia in C57BL/6 mice is associated with T cell-dependent (IgG)
      and T cell-independent (IgM) B-cell responses to MDA-LDL.

PMID- 17438417
TI  - Bacteria in Crohn's disease: mechanisms of inflammation and therapeutic
      implications.
AB  - Microbial agents are implicated in each of the most prevalent etiologic
      hypotheses of Crohn's disease. Although chronic infection with a specific,
      persistent pathogen cannot be excluded, it is more likely that Crohn's disease is
      caused by an overly aggressive immune response to normal commensal enteric
      bacteria. The complex, predominantly anaerobic microbiota in the distal ileum and
      colon provide a constant source of antigens and adjuvants that stimulate chronic
      immune-mediated inflammation in genetically susceptible hosts. Host genetic
      susceptibility in the form of defective mucosal barrier function, bacterial
      killing or processing can lead to enhanced exposure to luminal bacteria and their
      immunologically active components, whereas defective immunoregulation can lead to
      lack of appropriate immunosuppression. Either process can lead to overly
      aggressive T-cell responses to normal bacteria that causes tissue damage.
      Transient infection with pathogenic organisms could serve as environmental
      triggers to initiate inflammatory responses that are perpetuated in susceptible
      hosts by commensal microbial antigens. In addition, commensal bacteria such as
      Escherichia coli recovered from the ileum of patients with recurrent Crohn's
      disease after resection can contain virulence factors that mediate epithelial
      attachment, invasion, and resistance to killing. Finally, Western diet,
      antibiotic use, hygiene, and public health practices may have altered the balance
      of beneficial versus aggressive microbial species. Crohn's disease patients
      exhibit enhanced humoral and T-cell responses to common commensal bacterial and
      fungal antigens. These observations may help identify clinically relevant patient
      subsets and suggest novel therapeutic approaches to restore a beneficial balance
      of enteric microbiota, enhanced microbial killing, and inhibit aggressive T-cell
      responses to microbial antigens.

PMID- 17438418
TI  - Effects of bacteria on the enteric nervous system: implications for the irritable
      bowel syndrome.
AB  - A unified scenario emerges when it is considered that a major impact of stress on
      the intestinal tract is reflected by symptoms reminiscent of the diarrhea
      predominant form of irritable bowel syndrome. Cramping abdominal pain, fecal
      urgency, and explosive watery diarrhea are hallmarks not only of diarrhea
      predominant irritable bowel syndrome, but also of infectious enteritis, radiation
      induced enteritis, and food allergy. The scenario starts with stress-induced
      compromise of the intestinal mucosal barrier and continues with microorganisms or
      other sensitizing agents crossing the barrier and being intercepted by enteric
      mast cells. Mast cells signal the presence of the agent to the enteric nervous
      system (ie, the brain-in-the-gut), which uses one of the specialized programs
      from its library of programs to remove the "threat." This is accomplished by
      stimulating mucosal secretion, which flushes the threatening agent into the lumen
      and maintains it in suspension. The secretory response then becomes linked to
      powerful propulsive motility, which propels the secretions together with the
      offending agent rapidly in the anal direction. Cramping abdominal pain
      accompanies the strong propulsive contractions. Urgency is experienced when
      arrival of the large bolus of liquid distends the recto-sigmoid region and
      reflexly opens the internal anal sphincter, with continence protection now
      provided only by central reflexes that contract the puborectalis and external
      anal sphincter muscles. Sensory information arriving in the brain from receptors
      in the rapidly distending recto-sigmoid accounts for the conscious sensation of
      urgency and might exacerbate the individual's emotional stress. The symptom of
      explosive watery diarrhea becomes self-explanatory in this scenario.

PMID- 17438419
TI  - Long-term variability of GDx VCC retinal nerve fiber layer thickness
      measurements.
AB  - PURPOSE: To evaluate the long-term variability of GDx VCC retinal nerve fiber
      layer (RNFL) thickness measurements. METHODS: The study enrolled a cohort of
      glaucoma suspects who did not develop any evidence of visual field damage or
      change in the appearance of the optic nerve during an average follow-up of 9.1+/
      3.2 years. Subjects underwent ocular imaging using the commercially available GDx
      VCC scanning laser polarimeter. At each visit, each eye was imaged 3 times.
      Subjects underwent repeated testing with GDx VCC at approximately 12-month
      intervals during their follow-up. In total, 255 examinations were obtained in 31
      eyes of 31 individuals during an average GDx VCC follow-up time of 26.0+/-8.9
      months. A random effects analysis of variance model was used to estimate
      intraclass correlation coefficients and long-term and short-term variability
      estimates. RESULTS: Intraclass correlation coefficients ranged from 0.77 to 0.86
      for GDx VCC parameters. Short-term variability estimates ranged from 2.45 to 3.89
      microm for RNFL thickness parameters, whereas the short-term variability estimate
      for the parameter Nerve Fiber Indicator was 3.71. Long-term variability was
      slightly higher than short-term variability for all parameters. For RNFL
      thickness parameters, long-term variability estimates ranged from 3.21 to 4.97
      microm, whereas for the parameter Nerve Fiber Indicator the long-term variability
      estimate was 4.93. CONCLUSIONS: RNFL measurements obtained with the GDx VCC were
      found to be highly reproducible in a long-term test-retest situation, supporting
      the use of this instrument for longitudinal assessment of the RNFL.

PMID- 17438420
TI  - Decreased plasma cortisol in response to intramuscular ACTH in ocular
      hypertensives and primary open-angle glaucomas.
AB  - PURPOSE: To determine if there is a difference in response of the adrenal gland
      to intramuscular adrenocorticotropic hormone (ACTH) between normals and ocular
      hypertensives (OHs) plus primary open-angle glaucomas (POAGs) without pigmented
      angles. METHODS: Intramuscular ACTH was given to 29 normals and 24 OH plus POAG
      hospitalized in a Clinical Study Unit. Blood samples were obtained at baseline (0
      hours) before administration of intramuscular ACTH and 4, 8, and 24 hours after
      administration of intramuscular ACTH for analysis of plasma cortisol/body mass
      index (BMI). RESULTS: The OH plus POAG group showed lower cortisol/BMI values
      compared with the normal group at 4, 8, and 24 hours with a significantly lower
      peak/BMI value (P=0.030). Multivariate analyses with the peak plasma cortisol/BMI
      level as the dependent variable showed that a lower peak plasma/BMI was
      associated with the OH plus POAG group. Also, a lower peak plasma cortisol/BMI
      level was associated with a lower 0-hour cortisol/BMI (Log). CONCLUSIONS:
      Compared with normals, the OH plus POAG subjects showed lower plasma cortisol
      levels in response to intramuscular ACTH. This observation suggests adrenal
      suppression in the OH plus OAG group.

PMID- 17438421
TI  - A comparison of structural measurements using 2 Stratus optical coherence
      tomography instruments.
AB  - PURPOSE: To compare measures of peripapillary retinal nerve fiber layer (RNFL)
      thickness, optic disc topography, and central foveal thickness generated using 2
      different Stratus optical coherence tomography (OCT) instruments. METHODS: Ten
      normal subjects and 10 glaucoma subjects were included. One randomly selected eye
      per subject was scanned consecutively using a fast RNFL thickness protocol, fast
      macular thickness map, and fast optic disc protocol by 2 experienced operators on
      2 instruments. The order of the machines and operators were randomized. The
      output power of each machine was measured using an optical power meter. For each
      OCT measurement 2 factor fixed effects analyses of variance were performed and a
      restricted maximum likelihood variance component analysis of the proportion of
      variance due to subject, operator, and machine was calculated. RESULTS:
      Significant differences (P<or=0.003) between OCT instruments were observed in
      average, superior, and inferior RNFL thickness and central foveal thickness
      values among normal eyes; and average and superior RNFL thickness and cup/disc
      area ratio values among glaucomatous eyes. Overall, the intermachine variability
      (0.0% to 16.4%) was larger than the interoperator variability (0.0% to 2.4%) for
      all OCT measurements. In the glaucoma group the variability due to machine
      differences was 2.6 microm for the average RNFL thickness, 5.7 microm for the
      superior RNFL thickness, 0 microm for the inferior RNFL thickness, 0.03 microm
      for the cup/disc area ratio, 0.01 microm for the cup/disc vertical ratio, and 2.8
      microm for the average foveal thickness. CONCLUSIONS: Measurements of RNFL
      thickness, optic disc topography, and central foveal thickness significantly
      differ between OCT instruments.

PMID- 17438422
TI  - Comparison of localized retinal nerve fiber layer defects between a low-teen
      intraocular pressure group and a high-teen intraocular pressure group in normal
      tension glaucoma patients.
AB  - PURPOSE: To compare the features of localized retinal nerve fiber layer (RNFL)
      defects between a low-teen intraocular pressure (IOP) group and a high-teen IOP
      group in normal-tension glaucoma (NTG) patients. METHODS: Seventy-seven eyes of
      77 NTG patients showing localized RNFL defects on RNFL photographs and
      corresponding visual filed defects at the initial visit to a glaucoma specialist
      were selected for this study. Patients with range of diurnal IOP within low-teen
      or high-teen in both eyes were included. All participants completed refraction,
      diurnal IOP measurement, central corneal thickness (CCT) measurement,
      stereoscopic disc photography, RNFL photography, and automated perimetry. On RNFL
      photograph, approximation of the defect to the macula (angle alpha) and width of
      the defects (angle beta) were measured to represent RNFL defects. The patients
      were divided into 2 groups according to the level of IOP. A low-teen group had
      highest IOP of <or=15 mm Hg (group A) and a high-teen group had lowest IOP of >15
      mm Hg (group B). Age at diagnosis, percentage of male patients, systemic disease,
      refraction, CCT, highest IOP, angle alpha, angle beta, and mean deviation and
      pattern standard deviation of visual field were compared between the 2 groups.
      RESULTS: Age at diagnosis of NTG, age distribution, percentage of male patients,
      systemic disease, spherical equivalent of refraction, CCT, mean deviation, and
      pattern standard deviation were not different between the 2 groups. Highest IOP
      was 13.8+/-1.2 mm Hg in group A and 19.2+/-1.4 mm Hg in group B (P<0.001). Angle
      alpha was significantly smaller in group A than in group B (37.0+/-14.0 vs.
      56.5+/-21.2 degrees, P<0.001), whereas angle beta was not different between the 2
      groups (39.9+/-17.9 vs. 37.5+/-15.9 degrees, P=0.54). There were no significant
      correlations between spherical equivalent and angle alpha (r=-0.03, P=0.82),
      between spherical equivalent and angle beta (r=-0.04, P=0.74), and between angle
      alpha and angle beta (r=-0.21, P=0.07). CONCLUSIONS: Localized RNFL defect was
      closer to the center of the macula in group A than in group B, whereas width of
      defects was not different between the 2 groups. These findings provide indirect
      evidence to suggest that more than one pathogenic mechanism may exist in the
      development of RNFL defects in NTG.

PMID- 17438423
TI  - The influence of learning effect on frequency doubling technology perimetry
      (Matrix).
AB  - PURPOSE: To determine learning effect in healthy patients without perimetric
      experience, tested with the frequency doubling technology perimetry, with the new
      model Matrix. PATIENTS AND METHODS: Frequency doubling technology in the 30-2
      threshold mode was performed on 37 healthy subjects. Each subject was tested
      twice in different sessions. The test always began with the right eye (RE) and
      continued with the left eye (LE). To evaluate learning effect the results of the
      REs at the first session were compared with those of the LE. The following
      parameters were evaluated: foveal threshold (FT), reliability indexes, mean
      defect (MD), pattern standard deviation (PSD), glaucoma hemifield test (GHT),
      duration of examination. RESULTS: At the first session the average values of RE
      were FT=30.81 db, MD=-1 db, PSD=3.01 db, and duration of the examination=383.27
      "and of LE were FT=30.73, MD=-0.79 db, PSD=2.97 db, and duration of examination
      382.62." At the second session the average values of RE were FT=32.22 db,
      MD=+0.16 db, PSD 2.75 db, and duration of examination=374.97 db. The reliability
      was different and the GHT between the RE and LE in the first and second session
      was also different. CONCLUSIONS: A learning effect was observed between the first
      and the second sessions and the results of the GHT appeared improved. This above
      all should be taken into account when considering the clinical use of this test
      to avoid erroneous diagnostic conclusions.

PMID- 17438424
TI  - Glaucoma detection by Stratus OCT.
AB  - PURPOSE: To investigate the diagnostic accuracy of retinal nerve fiber layer
      thickness (RNFLT) summary report parameters from Stratus optical coherence
      tomography (OCT) in glaucoma patients. PATIENTS AND METHODS: We obtained Stratus
      OCT measurements of peripapillary circle scans (average values) of the regular
      image resolution "FAST RNFLT" protocol, and of 1 circle scan of the high
      resolution "RNFLT" protocol in one eye of each of 62 glaucoma patients with mild
      or moderate visual field (VF) loss and 90 healthy subjects. Sensitivity,
      specificity, and diagnostic accuracy [(true positive+true negative)/all] were
      evaluated for all summary report parameters including the newer (eg, "Imax," the
      maximum thickness point in the inferior quadrant) at the normative limits of the
      Stratus OCT. RESULTS: The diagnostic accuracy of full circle RNFLT using the 5%
      normal limit was 89% with the FAST RNFLT and 87% with the RNFLT protocol; this
      was at least as good as any other parameter. The diagnostic performance of the 2
      protocols did not differ significantly for most parameters. In eyes with mild VF
      loss (n=39) diagnostic sensitivities reached 72% and 77% at specificities >or=95%
      using the FAST RNFLT and RNFLT protocol, respectively. CONCLUSIONS: The
      diagnostic accuracy of the full circle RNFLT was as good as any Stratus OCT
      parameter on the basis of the peripapillary RNFL thickness measurements,
      including localized measurements. The sensitivity was moderately high in patients
      with mild glaucomatous VF loss. There seems to be room for further development of
      OCT interpretation tools for early diagnosis of glaucoma.

PMID- 17438425
TI  - Diurnal fluctuation and concordance of intraocular pressure in glaucoma suspects
      and normal tension glaucoma patients.
AB  - PURPOSE: The study objective was to determine the concordance of intraocular
      pressure (IOP) in glaucoma suspects (GS) and normal tension glaucoma (NTG)
      patients. METHODS: This was a retrospective review of diurnal curves of untreated
      GS and NTG patients. No subject had IOP greater than 21 mm Hg. We defined GS
      patients as having suspicious optic nerves with normal visual fields, and NTG
      patients as having glaucomatous optic nerves with associated visual field loss.
      Goldmann applanation tonometry was performed at 10:00, 13:00, 16:00, 19:00,
      22:00, and 07:00. Linear association of OD and OS IOP was estimated using Pearson
      correlation coefficient (r). The diurnal period was divided into 7 time intervals
      of 3, 6, 9, 12, 15, 18, and 21 hours, and the absolute difference in change in
      IOP between fellow eyes and probability that it was within 3 mm Hg were
      calculated. RESULTS: The study included 68 GS and 95 NTG subjects. The diurnal
      curves of the OD and OS showed a parallel course in both groups. The average
      correlations (r) of OD and OS IOP over the 6 time points were 0.78 and 0.81 for
      GS and NTG, respectively. The mean absolute difference in IOP change between OD
      and OS over the 6 time intervals ranged between 1.4 and 1.9 mm Hg for GS, and 1.3
      and 1.5 mm Hg for NTG subjects. The probability that this difference was within 3
      mm Hg ranged between 87% and 94% for GS, and 86% and 93% for NTG subjects.
      CONCLUSIONS: The diurnal variation in IOP between the 2 eyes in GS and NTG is
      largely concordant in approximately 90% of the time.

PMID- 17438426
TI  - Lifetime visual disability in open-angle glaucoma and ocular hypertension.
AB  - PURPOSE: To study how many of the patients with treated glaucoma or ocular
      hypertension go blind during their lifetime and which factors are associated with
      blindness. PATIENTS: The data on 106 consecutive patients who had died between
      1991 and 2002 was retrospectively evaluated. At diagnosis 39 patients had primary
      open-angle glaucoma, 27 had exfoliation glaucoma, and 40 had ocular hypertension.
      METHODS: Clinical records and causes of death were reviewed. Visual disability at
      the last visit before death was evaluated. Outcome measures were visual handicap
      and blindness based on visual acuity and/or visual fields. RESULTS: At the last
      visit, 17 patients [16%, 95% confidence interval (CI) 9-23] were visually
      handicapped. Thirteen patients (14%) were bilaterally blind. Glaucoma was the
      cause of blindness in one or both eyes in 16 patients (15%, 95% CI 8-22) and in
      both eyes in 6 patients (6%, 95% CI 1-10). In the analysis of only 1 eye of each
      patient, the cumulative incidence of glaucoma-caused blindness was 6% (95% CI 2
      11) at 5 years, 9% (95% CI 4-15) at 10 years, and 15% (95% CI 9-23) at 15 years.
      An advanced stage of glaucoma at diagnosis, fluctuation in intraocular pressure
      during treatment, the presence of exfoliation syndrome, and poor patient
      compliance increased the occurrence of blindness. Positive family history of
      glaucoma and vascular causes of death had no effect on visual outcome.
      CONCLUSIONS: Glaucoma-caused blindness was associated with an advanced stage of
      glaucoma at diagnosis, fluctuation of intraocular pressure during treatment, the
      presence of exfoliation syndrome, and poor patient compliance. The risk of going
      blind from glaucoma in both eyes was 6%.

PMID- 17438427
TI  - Systemic high-sensitivity C-reactive protein levels in normal-tension glaucoma
      and primary open-angle glaucoma.
AB  - PURPOSE: To determine the systemic high-sensitivity C-reactive protein (hsCRP)
      level in patients with normal tension glaucoma (NTG) and primary open-angle
      glaucoma (POAG). MATERIALS AND METHODS: With the exclusion of patients with
      cardiovascular and other systemic diseases, 40 patients with NTG, 40 with POAG,
      and 40 normal controls were enrolled in this study. Each patient underwent blood
      sampling for hsCRP, biochemistry, and lipid profile analysis. RESULTS: Each group
      had similar demographic parameters including the age, sex, body mass index, heart
      rate, and blood pressure. There was no statistically significant difference in
      the hsCRP and biochemistry results between the 3 groups. The lipid profile
      exhibited a mild elevation in the patients with POAG. CONCLUSIONS: Our data
      revealed no difference in the hsCRP level between NTG, POAG, and normal controls
      after exclusion of patients with cardiovascular and other systemic diseases.
      Systemic vascular inflammation may not be a major cause in the pathogenesis of
      glaucoma in those without histories of cardiovascular diseases.

PMID- 17438428
TI  - Corneal endothelial cell changes after trabeculectomy and deep sclerectomy.
AB  - PURPOSE: To compare the effect of trabeculectomy and deep sclerectomy on the
      corneal endothelium. METHODS: This prospective comparative study investigated 62
      eyes of 62 patients scheduled for a single trabeculectomy (n=18), a single deep
      sclerectomy (n=14), a combined trabeculectomy and phacoemulsification (n=11), or
      a combined deep sclerectomy and phacoemulsification (n=19). Exclusion criteria
      were history of corneal disease, ocular trauma, inflammation, or previous
      glaucoma or cataract surgery. Preoperative, 3-month and 1-year postoperative
      noncontact specular microscopies were performed on central and superior corneas.
      Endothelial cells were counted with a computer-assisted analyzer. RESULTS: In
      central cornea, a statistically significant postoperative endothelial cell loss
      was found after trabeculectomy and deep sclerectomy (alone and combined with
      cataract extraction) at 3 and 12 months. Cell loss was 7% after penetrating
      surgery and 2.6% after nonpenetrating surgery (noncombined surgeries). This
      difference in cell loss was statistically significant. Cell loss increased
      significantly over the course of the study at 12 months (9.6% and 4.5%,
      respectively). Cell loss was also significantly higher after trabeculectomy than
      sclerectomy in upper cornea only in noncombined surgeries. No statistically
      significant difference in coefficient of variation of cell size (CV) and
      percentage of cell hexagonality (Hex %) was noted. CONCLUSIONS: Endothelial cell
      loss was moderate 3 and 12 months after glaucoma surgery. However, it was greater
      after trabeculectomy, suggesting less corneal damage after deep sclerectomy. This
      observation deserves further clinical study.

PMID- 17438429
TI  - Continuous intraocular pressure (IOP) measurement during glaucoma drainage device
      implantation.
AB  - PURPOSE: To measure the effect of the implantation of a glaucoma drainage device
      on the intraocular pressure (IOP) during the implantation surgery. METHOD: We
      implanted telemetry devices into 1 eye each of 3 white New Zealand rabbits. Once
      the telemetry was found to be working and the rabbits had fully recovered from
      surgery, we implanted a glaucoma drainage device into the same eye while
      continually monitoring the IOP with the telemetry devices. RESULTS: During
      surgery IOP was extremely variable, however, extremely high pressures were
      recorded in association with suturing and viscoelastic injection. DISCUSSION: The
      fact that pressures are significantly raised during some surgical events should
      make surgeons aware that manipulations need to be kept as short as possible to
      prevent further potential damage to glaucomatous optic nerves. There is a
      possibility of dramatically raising the IOP during surgery, specifically in
      complicated cases requiring prolonged manipulation and/or forcible deepening of
      the anterior chamber. In such cases, it may be a good idea to time the duration
      of manipulations to prevent prolonged episodes of elevated IOP.

PMID- 17438430
TI  - Oxidative stress in glaucoma: a burden of evidence.

PMID- 17438431
TI  - The use of local anesthetic techniques for closed forearm fracture reduction in
      children: a survey of academic pediatric emergency departments.
AB  - BACKGROUND: Although local anesthetic techniques (hematoma blocks, nerve blocks,
      intravenous regional anesthesia) for forearm fracture reduction are well
      described and commonly used in adults, it is unclear how often these techniques
      are used in children. OBJECTIVE: To characterize the use of local anesthesia for
      pediatric closed forearm fracture reduction by pediatric and orthopedic
      physicians practicing in teaching hospitals in Canada and the United States.
      METHODS: An on-line survey targeting physicians practicing in hospitals with
      pediatric emergency medicine (PEM) fellowships in Canada and the United States
      was sent to the PEM fellowship director and orthopedic department head at each
      hospital. RESULTS: Sixty-three orthopedic surgeons and 69 PEM physicians were
      invited to participate in the survey, and 63% responded of all invited
      participants. All respondents routinely use sedation for forearm fracture
      reduction. Local anesthesia is used by 78% of respondents (55% rarely, 28%
      sometimes, and 17% frequently). Hematoma blocks are used by 92% of respondents
      who use local anesthesia; 20% use Bier blocks, and 2% use cubital blocks. Among
      respondents who never use local anesthesia, all believe that sufficient analgesia
      is obtained from procedural sedation alone, and 35% believe that local anesthesia
      is ineffective. CONCLUSIONS: Local anesthetic techniques are used only
      occasionally by those surveyed. More studies examining the use of local
      anesthesia for forearm fractures in children are necessary to evaluate the need
      for more widespread use.

PMID- 17438432
TI  - Evaluation of a child guidance model for visits for mental disorders to an inner
      city pediatric emergency department.
AB  - BACKGROUND: To address a rising trend of emergency department (ED) visits for
      mental disorders (VMD), our ED implemented a child guidance model for their
      efficient evaluation and disposition. OBJECTIVES: The main objective of our study
      was to evaluate the impact of the child guidance model on the ED length of stay
      (LOS) and ED costs on children with VMD. METHODS: We conducted a retrospective
      chart analysis on 1031 VMD visits made to an inner-city tertiary care pediatric
      ED in 2002 (1.4% of the total 2002 ED visits). We collected demographic and LOS
      information on all VMD visits. The child guidance model was implemented June
      2002, after which we divided the VMD cases into 2 groups based on the presence or
      absence of the model. We performed a cost analysis to assess the impact of the
      model on LOS and determined the opportunity costs of prolonged LOS of the VMD
      visits as compared with 500 non-VMD visits. RESULTS: The average LOS of VMD
      visits was longer than that of the 500 non-VMD visits (236.04 minutes +/- 162.82
      vs. 134.69 minutes +/- 95.19; mean difference, 101.34 minutes; P = 0.001). The
      LOS was significantly reduced after the model was implemented (259.49 minutes +/-
      171.12 vs. 216.39 +/- 152.95 minutes, P = 0.00). The lost revenue due to extended
      VMD LOS was calculated as opportunity costs of $201,173.30, whereas the cost
      savings during the study period due to reduced LOS after the model was
      implemented was $10,651. CONCLUSIONS: This study suggests that children with VMD
      visits contribute a substantial resource burden in the ED, and focused
      interventions such as the child guidance model in the ED can significantly
      decrease LOS and reduce ED costs.

PMID- 17438433
TI  - Pediatric Procedural Sedation in the Community Emergency Department: results from
      the ProSCED registry.
AB  - OBJECTIVES: Emergency department procedural sedation practices for children have
      been reported for pediatric tertiary care centers. This report describes these
      same practice patterns and outcomes for community hospital-based general
      emergency physicians (EPs) in their treatment of pediatric patients. METHODS: The
      Procedural Sedation in the Community Emergency Department registry is a
      prospective observational database composed of consecutive EP-directed procedural
      sedation cases in community hospitals. Information on sedation cases is collected
      at the time of the patient encounter and entered into an Internet-accessed
      database. RESULTS: A total of 1028 procedural sedations were performed on 977
      patients at 14 study sites, with 341 procedures performed in 339 patients younger
      than 21 years. The most common specified pediatric procedures performed included
      laceration repairs (n = 86, 25%), shoulder relocations (n = 78, 23%), and
      fracture care of the upper extremity (n = 56, 16%). Medications used included
      ketamine (n = 141, 41%), midazolam (n = 10, 32%), etomidate (n = 54, 16%),
      fentanyl (n = 51, 15%), and propofol (n = 47, 14%). Complications were reported
      in 2 cases (0.6%), 1 episode of apnea requiring a reversal agent and 1 episode of
      hypoxia responsive to supplemental oxygen. Of procedures attempted, 339 (99.4%)
      were successfully completed. Emergency physicians both directed the sedation and
      performed the procedure in 252 cases (74%), whereas in another 69 cases (20%),
      they directed the sedation for another physician performing the procedure. In 20
      cases (5.8%), the EP directed sedation for a painless diagnostic study.
      CONCLUSIONS: Community EPs in the Procedural Sedation in the Community Emergency
      Department registry deliver safe and effective pediatric sedation using a broad
      selection of agents.

PMID- 17438434
TI  - Parental administration of analgesic medication in children after a limb injury.
AB  - OBJECTIVE: To document parental administration of analgesic medication to
      children with pain from acute limb injury before coming to the emergency
      department (ED). METHODS: Research assistants interviewed parents of children 0
      to 18 years old who presented to the ED with acute limb injury, asking about
      analgesic use before arriving to the ED. Parents were also asked for personal and
      demographic information. Parents who did not give pharmacological analgesia were
      asked why they decided not to administer medications. All parents were asked if
      they will administer analgesia in the future. RESULTS: A total of 72% of parents
      administered analgesia (pharmacological or others) to their children. Only 28% of
      the children received pharmacological analgesics before arriving to the ED.
      Child's mean age was higher for the group receiving medications, compared with
      those not receiving medications (99 +/- 50 vs 122 +/- 52 months, respectively; P
      = 0.005). The main parental concern about analgesic use was of potential masking
      of the clinical signs and symptoms before being seen by a physician. CONCLUSIONS:
      Prehospital analgesic administration by parents is mainly nonpharmacological
      largely because of parental concern of interference with medical assessment or
      underestimating the child's pain. Parental concern of masking symptoms and
      parental perception of no pain in a child were significant factors in determining
      parental comfort level in using pharmacological analgesics.

PMID- 17438435
TI  - Accuracy of weight estimation methods for children.
AB  - OBJECTIVES: To evaluate differences in accuracy of 2 weight estimation methods
      for children when compared with measured weights: the Broselow-Luten tape
      (patient's height as the predictor) and the devised weight estimation method
      (DWEM) (patient's height and body habitus as predictors). METHODS: Information
      was obtained prospectively on a convenience sample of patients presenting through
      triage on nonconsecutive days at the Children's Hospital Emergency Department.
      Weight was measured in kilograms, and a measured length or height in centimeters
      was obtained, as well as 2 independent assessments of body habitus. Weights were
      then estimated using the Broselow-Luten tape and the DWEM. This study evaluated 4
      separate weight classes: less than or equal to 10 kg, 10.1 to 20 kg, 20.1 to 36
      kg, and 36.1 kg or more. One hundred children were recruited into each weight
      class, for a total of 400 children. Comparisons of estimations with measured
      weights were made using the Pearson correlation coefficient method. Mean
      percentage errors were calculated for weight estimations by both methods.
      RESULTS: Both the Broselow-Luten and DWEM weight estimations when compared with
      measured weights showed statistical correlation (using the Pearson correlation
      coefficient). However, the Broselow-Luten method had a negative mean percentage
      error in all weight classes, and the DWEM had a negative mean percentage error in
      classes greater than 20 kg, indicating an underestimation of weight in those
      classes. CONCLUSIONS: Although both the Broselow-Luten and DWEM weight
      estimations show statistical correlation with measured weights, the Broselow
      Luten method underestimates weights in all weight classes, and the DWEM
      underestimates weights in the weight classes greater than 20 kg.

PMID- 17438436
TI  - Rhinopharyngeal B-cell non-hodgkin lymphoma: unusual presentation with massive
      hematemesis.
AB  - Lymphomas are the third most frequent type of childhood cancer after acute
      leukemias and brain tumors. Symptoms at diagnosis are extremely different
      depending on several factors such as histological subtype, disease extent, and
      site of tumor. We report an unusual presentation describing a case of epistaxis
      of the posterior nasal fossa with severe hematemesis.

PMID- 17438437
TI  - Cardiotoxicity associated with accidental bupropion ingestion in a child.
AB  - Bupropion, an atypical antidepressant commonly used for depression and smoking
      cessation, is well known to cause seizures in both therapeutic use and overdose,
      but cardiac effects have been reported as minimal, usually sinus tachycardia. We
      describe an ingestion of bupropion estimated to be greater than 2 g by a 3-year
      old boy that resulted in seizures. The child was decontaminated with whole bowel
      irrigation (WBI), and he experienced aspiration of polyethylene glycol and
      electrolyte solution used for the WBI. The patient ultimately developed
      hypotension and bradycardia requiring cardiopulmonary resuscitation due to the
      effects of the bupropion combined with the complications of WBI. In contrast to
      previous literature, which showed few clinical effects aside from seizures from
      ingestion of bupropion by children, our case highlights the dangers of pediatric
      bupropion ingestion and highlights risks of WBI.

PMID- 17438438
TI  - Presentation of systemic lupus erythematosus in emergency department.
AB  - Systemic lupus erythematosus (SLE) is a multisystem inflammatory disease that is
      often difficult to diagnose in the emergency department. It is an autoimmune
      disease with great variability in presentation and course. Moreover, the atypical
      or incomplete presentation is common in children and can result in delay in
      diagnosis. Consideration of the possibility of SLE is important when evaluating a
      patient with symptoms and/or signs suggesting multisystem disease. The emergency
      physician must maintain a high degree of suspicion for the early diagnosis and
      management of this important condition. We present 3 children who presented to
      emergency department with different initial manifestations of SLE.

PMID- 17438439
TI  - Acute acalculous cholecystitis in a child returning from the Ivory Coast.
AB  - Acute cholecystitis is an uncommon occurrence in children. Acute acalculous
      cholecystitis (AAC) has various etiology; among them are a wide variety of
      infectious agents. We report the case of a 7-year-old child who presented AAC due
      to plasmodium falciparum infection. The causes of AAC are discussed.

PMID- 17438440
TI  - Haemophilus influenzae Type f sepsis in an immunocompetent child.
AB  - Invasive infections due to Haemophilus influenzae non-type b have been reported
      to be on the increase with the decline in invasive H.influenzae type b infections
      after the introduction of the conjugate H.influenzae type b vaccine. We report a
      case of H. influenzae type f sepsis in a fully immunized, immunocompetent, and
      previously healthy 9-month-old child.

PMID- 17438441
TI  - ECGs in the ED.

PMID- 17438442
TI  - Alternative airway devices for use in children requiring prehospital airway
      management: update and case discussion.
AB  - This manuscript reviews the latest literature on alternative airways for use in
      children requiring prehospital airway management. Case discussions serve as a
      springboard for discussion of alternatives to bag-mask ventilation and
      endotracheal intubation for management of ventilation in infants and children in
      the prehospital setting. Few airway procedures have been studied with any rigor
      in this setting, and most of the data that are available are extrapolated from
      adults. Laryngeal mask airway may be the best alternative airway with the most
      promise to add to the armamentarium of the prehospital provider, but no
      controlled trial to date has been conducted.

PMID- 17438444
TI  - Guidelines to practice: the process of planning and implementing a pediatric
      sedation program.
AB  - OBJECTIVE: Pediatric sedation practices vary among institutions and even within
      the same institution depending on providers and location. We planned to implement
      a pediatric procedural sedation program for a tertiary care pediatric emergency
      department to standardize sedation practices among emergency physicians. METHODS:
      An interactive contextual planning model was adapted, and several tasks were
      initiated simultaneously. The director of pediatric emergency medicine and
      clinical director of the institution approved the proposal for the sedation
      program. Needs assessment surveys and focus group interviews were conducted to
      identify educational needs of the target audience and infuse a sense of
      ownership. A grant was obtained from the institution because the budget exceeded
      available divisional funds. Other pediatric sedation guidelines and published
      literature were used to produce a sedation handbook and pocket card. Interim
      approval was obtained from the Drugs and Therapeutics Committee and the Patient
      Care Committee. RESULTS: The program was successfully implemented after all
      physicians and nurses working in the emergency department attended a half-day
      sedation course and completed a multiple-choice examination. Random chart audits
      verify that the emergency physicians are performing almost all procedural
      sedations now as per protocol. CONCLUSIONS: Implementing a structured program
      facilitates guideline adherence. Adapting a flexible contextual planning model
      was successful in translating guidelines to practice where resources were
      limited, and the target audience was highly trained adult learners.

PMID- 17438445
TI  - Is cardiopulmonary resuscitation warranted in children who suffer cardiac arrest
      post trauma?
AB  - The use of cardiopulmonary resuscitation (CPR) is accepted universally for
      patients with cardiovascular compromise. However, outcomes from CPR in subsets of
      trauma patients may not be as good as initially thought. This article reviews the
      literature on outcomes from traumatic arrest in both adults and children.
      Outcomes for adults and children are similar, although the types of injuries may
      differ. Patients with asystolic arrest at the scene have very poor survival, and
      those who do survive sustain severe neurological injury. Recognizing that most
      providers would feel uncomfortable at not attempting resuscitation, the length
      and degree of aggressiveness of CPR is addressed. Finally, we discuss possible
      reasons to resuscitate. Organ donation and the ethics of nontherapeutic
      ventilation and other strategies to increase the donor pool are discussed. We
      hope to stimulate discussion around a very difficult issue.

PMID- 17438447
TI  - Errors in diagnosing salt poisoning in children.

PMID- 17438448
TI  - What's new in shock, May 2007?

PMID- 17438449
TI  - Sex differences in the long-term outcome after a severe thermal injury.
AB  - We have recently shown that during the acute phase, postburn female pediatric
      burn patients had significantly increased levels of anabolic hormones with an
      associated decreased hypermetabolism leading to a significant shorter intensive
      care unit stay compared with male patients. The aim of the present study was to
      determine possible differences between girls and boys in body composition,
      hypermetabolism, and hormone pattern in the long term. Sixty-two children (1-16
      years old) who sustained a severe thermal injury (>or=40% total body surface
      area) were included into the study. Patients were further divided into girls (n =
      22) and boys (n = 40). Patient demographics, nutritional support, and mortality
      were noted. Resting energy expenditure (REE) was measured by indirect
      calorimetry, body composition by dual-energy x-ray absorptiometry (Hologic Inc,
      Waltham, Mass) at discharge, 3, 6, 9, 12, 18, and 24 months after burn. In
      addition, blood was drawn at the same time points, and serum hormones were
      measured. There were no significant differences between girls and boys for
      demographics, nutritional intake, or concomitant injuries. Predicted REE was
      significantly decreased in girls at discharge, 6, 12, and 18 months postburn (P <
      0.05). Dual-energy x-ray absorptiometry scan showed that girls had improved
      change in bone mineral content and percent fat compared with boys (P < 0.05).
      There were no differences in changes in height, body weight, lean body mass, and
      total fat between groups. Girls had significantly higher levels of insulinlike
      growth factor 1, insulinlike growth factor binding protein 3, free thyroxine
      index, T4, and insulin when compared with boys (P < 0.05). No differences were
      found for T3 uptake, osteocalcin, cortisol, growth hormone, and parathyroid
      hormone (PTH) between groups. Data indicate that girls have a reduced REE
      associated with changes in bone content and endogenous anabolic hormones.

PMID- 17438450
TI  - Alterations in inflammatory capacity and TLR expression on monocytes and
      neutrophils after cardiopulmonary bypass.
AB  - Cardiopulmonary bypass (CPB) is associated with immune paresis, which predisposes
      to the development of postoperative sepsis. The aims of this study were to
      characterize the ex vivo cytokine responses to bacterial cell wall components in
      whole blood from patients undergoing CPB and to determine whether altered
      leukocyte expression of Toll-like receptors (TLRs) is involved in immune paresis
      after CPB. We recruited 6 patients undergoing routine cardiac surgery with CPB.
      Preoperatively, at the end of CPB and 20 h later, blood was obtained,
      anticoagulated, and leukocyte surface expression of CD14, TLR2, and TLR4 was
      quantified by flow cytometry. In addition, blood was incubated at 37 degrees C in
      the presence of peptidoglycan (PepG) and/or lipopolysaccharide (LPS), and plasma
      cytokines were measured by enzyme immunoassay. At the end of CPB, ex vivo
      production of tumor necrosis factor alpha, interleukin (IL) 1beta, IL-8, and IL
      10 in response to PepG or LPS was virtually abolished (P < 0.05). The following
      day, there was recovery of all cytokine responses to PepG. Tumor necrosis factor
      alpha and IL-1beta responses to LPS partially recovered, whereas IL-8 and IL-10
      responses recovered. At the end of CPB, there was more than 50% reduction in
      neutrophil TLR2 and TLR4 expression (P < 0.05), with recovery to baseline the
      following day. There was a 29% reduction in monocyte TLR4 expression at the end
      of CPB (P < 0.05) and more than 120% increase in monocyte TLR2 and 4 expression
      the following day (P < 0.05). In conclusion, reduced ex vivo production of
      cytokines cannot be fully accounted for by downregulation of TLR expression,
      although receptor upregulation may contribute to the later recovery of
      responsiveness.

PMID- 17438451
TI  - Pancreatic cellular injury after cardiac surgery with cardiopulmonary bypass:
      frequency, time course and risk factors.
AB  - Although often clinically silent, pancreatic cellular injury (PCI) is relatively
      frequent after cardiac surgery with cardiopulmonary bypass; and its etiology and
      time course are largely unknown. We defined PCI as the simultaneous presence of
      abnormal values of pancreatic isoamylase and immunoreactive trypsin (IRT). The
      frequency and time evolution of PCI were assessed in this condition using assays
      for specific exocrine pancreatic enzymes. Correlations with inflammatory markers
      were searched for preoperative risk factors. One hundred ninety-three patients
      submitted to cardiac surgery were enrolled prospectively. Blood IRT, amylase,
      pancreatic isoamylase, lipase, and markers of inflammation (alpha1-protease
      inhibitor, alpha2-macroglobulin, myeloperoxidase) were measured preoperatively
      and postoperatively until day 8. The postoperative increase in plasma levels of
      pancreatic enzymes and urinary IRT was biphasic in all patients: early after
      surgery and later (from day 4 to 8 after surgery). One hundred thirty-three
      patients (69%) experienced PCI, with mean IRT, isoamylase, and alpha1-protease
      inhibitor values higher for each sample than that in patients without PCI. By
      multiple regression analysis, we found preoperative values of plasma IRT >or=40
      ng/mL, amylase >or=42 IU/mL, and pancreatic isoamylase >or=20 IU/L associated
      with a higher incidence of postsurgery PCI (P < 0.005). In the PCI patients, a
      significant correlation was found between the 4 pancreatic enzymes and urinary
      IRT, total calcium, myeloperoxidase, alpha1-protease inhibitor, and alpha2
      macroglobulin. These data support a high prevalence of postoperative PCI after
      cardiac surgery with cardiopulmonary bypass, typically biphasic and clinically
      silent, especially when pancreatic enzymes were elevated preoperatively.

PMID- 17438452
TI  - Macrophage migration inhibitory factor (MIF) in meningococcal septic shock and
      experimental human endotoxemia.
AB  - Macrophage migration inhibitory factor (MIF) is a mediator of innate immunity and
      important in the pathogenesis of septic shock. Lipopolysaccharide (LPS) and tumor
      necrosis factor (TNF) alpha are reported to be inducers of MIF. We studied MIF
      and cytokines in vivo in patients with meningococcal disease, in human
      experimental endotoxemia, and in whole blood cultures using a newly developed
      sensitive and specific enzyme-linked immunosorbent assay. Twenty patients with
      meningococcal disease were investigated. For the human endotoxemia model, 8
      healthy volunteers were intravenously injected with 2 ng/kg Escherichia coli LPS.
      Whole blood from healthy volunteers was incubated with LPS or heat-killed
      meningococci. Macrophage migration inhibitory factor concentration in blood was
      increased during meningococcal disease and highest in the patients presenting
      with shock compared with patients without shock. Plasma concentration of MIF
      correlated with disease severity, the presence of shock and with the cytokines
      interleukin (IL) 1beta, IL-10, IL-12, and vascular endothelial growth factor, but
      not with TNF-alpha. MIF was not detected in blood in experimental endotoxemia,
      nor after stimulation of whole blood with LPS or meningococci, although high
      levels of TNF-alpha were seen in both models. In conclusion, MIF is increased in
      patients with meningococcal disease and highest in the presence of shock.
      Macrophage migration inhibitory factor cannot be detected in a human endotoxemia
      model and is not produced by whole blood cells incubated with LPS or
      meningococci.

PMID- 17438453
TI  - Altered levels and molecular forms of granzyme k in plasma from septic patients.
AB  - Granzyme K (GrK) is a member of a highly conserved group of potent serine
      proteases specifically found in the secretory granules of cytotoxic T lymphocytes
      and natural killer cells. Based on the report indicating that inter-alpha
      inhibitor proteins are the physiological inhibitors of GrK and on previous
      findings that showed a significant decrease in plasma inter-alpha inhibitor
      proteins in patients with sepsis, it was our aim to determine whether increased
      levels of uninhibited GrK would contribute to the development of sepsis. To test
      this hypothesis, a competitive enzyme-linked immunosorbent assay system was
      developed; and the levels of GrK were measured in plasma samples obtained from
      healthy controls and 2 sets of patients with sepsis: patients admitted to the
      emergency department with a putative diagnosis of sepsis and patients with severe
      sepsis enrolled in a clinical trial. In addition, the molecular form(s) of GrK
      present in these samples was analyzed by Western blot. The levels of GrK were
      significantly increased in emergency department patients compared with healthy
      controls and significantly decreased in patients with severe sepsis enrolled in a
      clinical trial compared with healthy controls. GrK was detected as high-molecular
      weight protein complexes in healthy controls but as complexes of lower molecular
      weight in the septic patients. The decrease in complex size correlated with the
      appearance of a band at 26 kDa similar to the size of free GrK. Our results
      indicate that plasma levels of GrK could serve as a useful diagnostic marker to
      stage sepsis, permitting better classification of septic patients and enabling
      targeting of specific treatments, and may play a functional role in the
      development of sepsis.

PMID- 17438454
TI  - Origin of immunomodulation after soft tissue trauma: potential involvement of
      extracellular heat-shock proteins.
AB  - Severe injury may lead to immunosuppression, multiple organ failure, and death.
      The aim of the study was to investigate the direct impact of soft tissue
      destruction on the development of trauma-associated immunomodulation. Hip surgery
      was considered to represent an isolated soft tissue trauma that allowed for the
      examination of changes taking place locally at the site of trauma or systemically
      with regard to monocyte function and leukocyte redistribution. Peripheral blood
      and wound fluid collected from the drains of 21 patients after hip surgery were
      analyzed to determine the cellular composition and/or the responsiveness of
      mononuclear cells (MNCs) to lipopolysaccharide (LPS). Different factors present
      in the wound fluids were tested for their capacity to modulate the MNC of healthy
      individuals with regard to cytokine and chemokine secretion. We found that
      various factors, including heat-shock protein (HSP) 60 and HSP70, were locally
      released at the site of soft tissue trauma and could be detected in wound fluids.
      The wound fluid-derived MNC (but not the peripheral blood-derived MNC) showed an
      impaired capacity to release TNF-alpha after LPS stimulation. Cell-free wound
      fluid suppressed in healthy individuals the LPS-induced TNF-alpha secretion by
      MNC. After surgery, granulocytosis was found in peripheral blood and in wound
      fluids, but monocytopenia was restricted to wound fluids. In parallel, wound
      fluids induced in healthy individuals the release by MNC of distinct chemokines
      specific for granulocytes and monocytes. These wound fluid-mediated effects of
      TNF-alpha suppression and chemokine induction could be mimicked by recombinant
      human HSP70 and, in part, by HSP60. Thus, tissue-derived factors, such as HSP70
      released after injury, suppress monocyte function and, therefore, might favor the
      development of immunosuppression after severe injury.

PMID- 17438455
TI  - Increases in serum macrophage migration inhibitory factor in patients with severe
      sepsis predict early mortality.
AB  - This prospective study aimed to delineate the association between the serum
      levels of macrophage migration inhibitory factor (MIF) and the risks of early
      mortality in 112 patients who presented with clinically severe sepsis. Previous
      studies showed that elevated serum MIF levels on the first day are associated
      with an increased risk of 28-day mortality. Nonsurvivors may be the sickest
      population on arrival. Not all patients with severe sepsis follow the same
      clinical pathway, however, and the sequential change in MIF might be an important
      predictor of mortality. We hypothesized that, for septic patients, in addition to
      serum MIF levels on day 1, the percentage of change in MIF between days 1 and 2
      after arriving in the emergency department predicts the probability of early
      mortality. Serum MIF levels were measured on days 1 (emergency department
      arrival) and 2 (24 h after arrival). Patients with a high percentage of increase
      between MIF levels on days 1 and 2 had higher 3-day (odds ratio, 1.8; 95%
      confidence interval, 1.2-2.6; P = 0.003) and 7-day mortalities (odds ratio, 1.4;
      95% confidence interval, 1.0-1.9; P = 0.03) after adjusting for age and day-1
      serum MIF levels. In conclusion, an increase in serum MIF from the first to
      second day of admission in patients with severe sepsis indicates a higher risk of
      early mortality; therefore, these patients need more aggressive therapeutic
      intervention.

PMID- 17438456
TI  - Mice depleted of alphabeta but not gammadelta T cells are resistant to mortality
      caused by cecal ligation and puncture.
AB  - The present study was undertaken to determine whether the mice depleted of
      alphabeta or gammadelta T cells show resistance to acute polymicrobial sepsis
      caused by cecal ligation and puncture (CLP). T-cell receptor beta knockout
      (betaTCRKO) and T-cell receptor delta knockout (deltaTCRKO) mice were used. An
      additional group of mice was treated with an antibody against the alphabeta T
      cell receptor to induce alphabeta T-cell depletion; a subset of alphabeta T cell
      deficient mice was also treated with anti-asialoGM1 to deplete natural killer
      (NK) cells. The mice underwent CLP and were monitored for survival, temperature,
      acid-base balance, bacterial counts, and cytokine production. The betaTCRKO mice
      and the wild-type mice treated with anti-beta T-cell receptor (anti-TCRbeta)
      antibody showed improved survival after CLP compared with wild-type mice. The
      treatment of alphabeta T cell-deficient mice with anti-asialoGM1further improved
      survival after CLP, especially when the mice were treated with imipenem. The
      improved survival observed in alphabeta T cell-deficient mice was associated with
      less hypothermia, improved acid-base balance, and decreased production of the
      proinflammatory cytokines interleukin (IL) 6 and macrophage inflammatory protein
      (MIP) 2. Compared with wild-type controls, the overall survival was not improved
      in deltaTCRKO mice. The concentrations of IL-6 and MIP-2 in plasma and cytokine
      mRNA expression in tissues were not significantly different between wild-type and
      deltaTCRKO mice. These studies indicate that mice depleted of alphabeta but not
      of gammadelta T cells are resistant to mortality in an acutely lethal model of
      CLP. The depletion of NK cells caused further survival benefit in alphabeta T
      cell-deficient mice. These findings suggest that alphabeta T and NK cells mediate
      or facilitate CLP-induced inflammatory injury.

PMID- 17438457
TI  - Fluid resuscitation in severe sepsis and septic shock: albumin, hydroxyethyl
      starch, gelatin or ringer's lactate-does it really make a difference?
AB  - The aim of this study was to investigate whether the type of i.v. fluid
      administered has an impact on outcome in an animal model of septic shock. The
      study included 28 anesthetized, invasively monitored, mechanically ventilated
      female sheep (29.5 +/- 4.0 kg), which received 0.5 g/kg body weight of feces into
      the abdominal cavity to induce peritonitis. During the surgical operation and 4 h
      after feces spillage, only Ringer's lactate (RL) was administered in all animals.
      Thereafter, animals were randomized to receive continuous infusions of RL (n = 7)
      alone or combined with either 20% albumin (n = 7, volume ratio to RL 1:10) or 6%
      hydroxyethyl starch (HES) (n = 7, volume ratio to RL 1:1), or gelatin alone (n=
      7, no volume limitation). Fluid resuscitation was titrated to maintain pulmonary
      artery occlusion pressure at baseline levels throughout the experiment. No
      antibiotics or vasoactive drugs were administered, and animals were monitored
      until their spontaneous death. Hemodynamic variables were better with HES and
      albumin than with the other fluids, as reflected by higher stroke volume, cardiac
      index, and oxygen delivery (all P < 0.05). Hydroxyethyl-starch-treated animals
      also had lower arterial lactate concentrations (P < 0.01). However, times to
      develop hypotension and oliguria were similar in all groups. Blood interleukin
      (IL) 6 concentrations were significantly increased in all groups. The mean
      survival time was similar in all groups. In this clinically relevant model of
      prolonged septic shock, albumin and HES solution resulted in higher cardiac
      output, oxygen delivery, and lower blood lactate levels than gelatin and RL;
      however, the choice of i.v. fluid did not affect outcome.

PMID- 17438458
TI  - Resuscitation with hydroxyethyl starch solution prevents nuclear factor kappaB
      activation and oxidative stress after hemorrhagic shock and resuscitation in
      rats.
AB  - Fluid resuscitation is vital for treating traumatic hemorrhagic shock (HS), but
      reperfusion is believed to have the adverse consequences of generating reactive
      oxygen species and inflammatory cytokines, both of which cause multiple organ
      dysfunctions. We investigated the effects of various resuscitation fluids on the
      changes of redox-sensitive molecules after HS and fluid resuscitation (HS/R). We
      induced HS by bleeding male Sprague-Dawley rats to a blood pressure of 30 to 40
      mmHg for 60 minutes. Thirty minutes later, the rats were killed (HS group) or
      immediately resuscitated with shed blood (HS + BL group), L-isomer lactated
      Ringer's solution (HS + LR group), or hydroxyethyl starch (HS + HES group). After
      HS, we found a significant increase in nuclear factor kappaB DNA binding
      activity, which was effectively inhibited using HES solution or blood
      resuscitation. Moreover, resuscitation with blood or LR solution, but not HES
      solution, induced significant oxidative stress, manifested by a high ratio of
      oxidized glutathione to reduced glutathione in the lungs, liver, and spleen. HS
      alone, however, did not increase the ratio of the oxidized glutathione to reduced
      glutathione in all organs. Although the protein expression of anti-apoptotic Bcl
      2 and pro-apoptotic Bax varied in different organs, we found that resuscitation
      using HES solution prevented the HS-induced reduction of the Bcl-2/Bax ratio in
      the heart. HES solution was an appropriate resuscitation fluid in reversing
      nuclear factor kappaB activation, maintaining the Bcl-2/Bax ratio, and preventing
      oxidative stress after acute HS.

PMID- 17438459
TI  - Effects of intra-abdominal administration of recombinant tissue plasminogen
      activator on coagulation, fibrinolysis and inflammatory responses in experimental
      polymicrobial peritonitis.
AB  - Peritonitis represents a procoagulant state because of activated coagulation and
      inhibited fibrinolysis. Intra-abdominal fibrin deposition-entrapping bacteria
      prevents bacterial spread but impairs bacterial clearance. Activating intra
      abdominal fibrinolysis by recombinant tissue-type plasminogen activator (r-tPA)
      early during peritonitis may enhance bacterial clearance and reduce inflammation.
      This study examines effects of abdominal r-tPA lavage on local and distant
      coagulation, fibrinolysis, and inflammatory responses in experimental
      polymicrobial peritonitis. Twenty-four hours after cecal ligation and puncture,
      mice were exposed to therapeutic abdominal lavage with varying doses of r-tPA or
      saline (controls). Coagulation, fibrinolysis, and inflammation were assessed in
      abdominal, systemic, and pulmonary compartments (n = 6 per group per time point).
      Survival was assessed during 96 h (n = 16 per group). Highest-dose (2 mg/mL) r
      tPA lavage caused immediate death. High-dose (0.5 mg/mL) r-tPA lavage increased
      fibrinolysis, demonstrated by low abdominal plasminogen activator inhibitor 1
      levels and elevated pulmonary tPA levels, resulting in reduced abdominal
      bacterial load, chemokine levels, leukocyte influx, and thrombin generation,
      along with less pulmonary fibrin depositions and organ damage on histological
      examination (P < 0.05 vs. saline lavage). Low-dose (0.05 mg/mL) r-tPA lavage
      showed hardly any effect compared with saline lavage. Adversely, abdominal and
      plasma interleukin (IL) 12 were elevated, whereas IL-10 levels were decreased
      after high-dose r-tPA lavage (P < 0.05 vs. saline). Survival rate was not
      affected by any dose of r-tPA lavage compared with saline lavage. Delayed local
      stimulation of fibrinolysis by peritoneal r-tPA lavage enhanced intra-abdominal
      bacterial clearance and reduced intra- and extra-abdominal coagulation responses
      in a dose-dependent manner. Survival rate was unaffected likely due to adverse
      changes in IL-12 and IL-10 levels.

PMID- 17438461
TI  - Disruption of skeletal myocytes initiates superoxide release: contribution of
      NADPH oxidase.
AB  - Generation of reactive oxygen species (ROS) as an early local reaction to muscle
      crush injury has frequently been predicted. However, although it is known that
      severe inflammatory reactions occurring after major muscle trauma originate
      mainly from early local incidents within the injured tissue, no detailed studies
      exist on the local generation of ROS in response to myocyte destruction thus far.
      Therefore, in this study, ROS formation after lethal mechanical damage was
      examined using a model of scraping injury to cultured C2C12 skeletal myocytes and
      superoxide detection by lucigenin chemiluminescence, nitrotetrazolium blue
      chloride reduction, or electron spin resonance spectroscopy. Mechanical rupture
      of myocytes resulted in an immediate release of superoxide from the damaged cells
      that could be substantially blocked by the superoxide scavengers superoxide
      dismutase (51%), tiron (95%), and MAMA/NO (93%) and by hypoxia (83% inhibition).
      Superoxide generation was primarily confined to the myocytes' membrane fraction
      and 7- to 8-fold enhanced by the addition of NADH or NADPH. The NADPH-enhanced
      superoxide generation could largely be diminished by the NAD(P)H oxidase
      inhibitors diphenyleneiodonium and apocynin in cell lysates (97% and 35%
      inhibition, respectively) and in isolated membrane fractions (61% and 63%
      inhibition). We thus conclude that immediately after myocyte damage, large
      amounts of superoxide are formed that predominantly originate from membrane-bound
      electron-transferring enzymes, especially NAD(P)H oxidase. This suggests a
      decisive role of ROS in the pathogenesis of tissue trauma, with superoxide being
      an initiator of the signaling mechanism from injured myocytes to the surrounding
      tissue and, potentially, to the whole body.

PMID- 17438460
TI  - Etanercept attenuates the development of cerulein-induced acute pancreatitis in
      mice: a comparison with TNF-alpha genetic deletion.
AB  - TNF-alpha plays a pivotal role in the pathogenesis of acute pancreatitis. Recent
      studies have shown that TNF-alpha inhibition significantly ameliorates the course
      of experimental acute pancreatitis, but in this context, the effects of
      Etanercept, a novel anti-TNF-alpha agent, have not been investigated so far. The
      aims of the present study are (i) to assess the effects of pharmacological
      inhibition of TNF-alpha by means of Etanercept on the inflammatory response and
      apoptosis in a murine model of necrotizing acute pancreatitis and (ii) to compare
      the results to those observed in TNF-alpha receptor 1 knockout (TNFR1-KO) mice.
      Necrotizing acute pancreatitis was induced in TNF-alpha wild type for TNFR1 (WT)
      and TNFR1-KO mice by intraperitoneal injection of cerulein (hourly x5, 50
      microg/kg). In another group of WT mice, Etanercept was administered (5 or 10
      mg/kg, s.c.) at 1 h after first cerulein injection. Control groups received
      saline treatment. After 24 h, biochemical, histological, and immunohistochemical
      evidences of acute pancreatitis developed in all cerulein-treated mice; apoptosis
      was also present in the pancreas. Contrarily, pancreatitis histological features,
      amylase and lipase levels, pancreas water content, and myeloperoxidase activity
      were reduced in a similar degree in Etanercept-treated and TNFR1-KO mice.
      Likewise, in these two groups, immunohistochemical stainings and terminal
      deoxynucleotidyltransferase-mediated UTP nick-end labeling assay were found
      negative. TNF-alpha receptor 1 gene deletion and Etanercept administration
      ameliorate the course of experimental acute pancreatitis in a similar degree.
      Future studies on clinical applications of Etanercept in pancreatitis seem
      promising.

PMID- 17438462
TI  - Muscarinic receptor-independent activation of cyclic adenosine monophosphate
      dependent protein kinase in rostral ventrolateral medulla underlies the
      sympathoexcitatory phase of cardiovascular responses during mevinphos
      intoxication in the rat.
AB  - As inhibitors of acetylcholinesterase, clinical presentations of poisoning from
      organophosphate compounds are generally believed to entail overstimulation by the
      accumulated acetylcholine on muscarinic receptors at peripheral and central
      synapses. That some patients still yielded to acute organophosphate poisoning
      despite repeated dosing of atropine suggests that cellular mechanisms that are
      independent of muscarinic receptor activation may also be engaged in
      organophosphate poisoning. The present study was undertaken to test the
      hypothesis that muscarinic receptor-independent activation of cyclic adenosine
      monophosphate-dependent protein kinase A (PKA) in rostral ventrolateral medulla
      (RVLM), a medullary site where sympathetic vasomotor tone originates and where
      the organophosphate poison mevinphos (Mev) acts, is involved in the
      cardiovascular responses exhibited during organophosphate intoxication. In
      Sprague-Dawley rats, microinjection bilaterally of Mev (10 nmol) into the RVLM
      significantly augmented PKA activity in ventrolateral medulla that was not
      antagonized by coadministration of an equimolar concentration (1 nmol) of
      atropine or selective muscarinic receptor type M1 (pirenzepine), M2
      (methoctramine), M3 (4-diphenyl-acetoxy-N-dimethylpiperidinium), or M4
      (tropicamide) inhibitor. Comicroinjection of two selective PKA antagonists (100
      pmol), N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide and
      (9R,10S,12S)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H
      diindolol[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-1][1,6]benzodiazocine-10-carboxylic
      acid, significantly blunted the initial sympathoexcitatory cardiovascular
      response and the accompanying augmentation of nitric oxide synthase (NOS I)
      expression in the ventrolateral medulla exhibited during Mev intoxication; the
      secondary sympathoinhibitory phase and associated elevation in NOS II expression
      were unaffected. We conclude that whereas a muscarinic receptor-independent
      augmentation of PKA activity in the ventrolateral medulla was manifested
      throughout acute Mev intoxication, this activation was preferentially involved in
      the sympathoexcitatory phase by an upregulation of NOS I expression.

PMID- 17438463
TI  - Hypertonic 15% sodium pyruvate offers no initial resuscitation advantage compared
      with 8% hypertonic NACl in sheep with multiple hemorrhages.
AB  - Initial fluid resuscitation of hemorrhagic shock might be enhanced by the
      infusion of monocarboxylate-energy substrates. We evaluated hemodynamics,
      metabolism, and fluid dynamics for initial resuscitation of hemorrhage using
      small volume 15% sodium pyruvate solution (HPY) compared with osmotically matched
      8% hypertonic saline (HS). Instrumented conscious sheep were hemorrhaged 25 mL/kg
      at time zero through 15 min (T0-T15) and 5 mL/kg for 5 min at T50 to T55 and T70
      to T75. Fluid resuscitation from T30 to T180 was performed by a computer
      controlled closed-loop system, which titrated infusion rate to a mean arterial
      pressure of 90 mmHg. Initial infusion was 4 mL/kg of either HPY or HS, followed
      by the administration of lactated Ringer. Both HPY and HS restored cardiac index
      similarly. The lactate/pyruvate ratio was used to assess metabolic debt and was
      significantly higher (T180), whereas oxygen delivery was significantly lower
      (T120) with HPY versus HS. Total fluid administered was similar, with 43.7 +/-
      6.2 mL/kg for HPY and 39.4 +/- 6.8 mL/kg for HS. Plasma volume was similarly
      increased and approached baseline values for both groups. Initial resuscitation
      with small volume HPY offered no hemodynamic or metabolic advantage compared with
      small volume HS when the fluids were infused to an end point pressure.

PMID- 17438464
TI  - Hypoxic preconditioning induces delayed cardioprotection through p38 MAPK
      mediated calreticulin upregulation.
AB  - The protective mechanisms of hypoxic preconditioning (HPC) involve the mitigation
      of cellular calcium overload in cardiomyocytes. The sarcoplasmic reticulum (SR)
      chaperone calreticulin (CRT) plays an important role in regulating calcium
      homeostasis and is upregulated by HPC. The goal of this study was to show whether
      the late cardioprotection of HPC is mediated by calreticulin upregulation and to
      demonstrate whether the calreticulin induction is mediated by p38 MAPK
      phosphorylation. Hypoxic preconditioning was induced by hypoxemic hypoxic
      exposure by a 24-h period of normoxic reoxygenation before undergoing LAD
      occlusion in rats or hypoxia/reoxygenation (H/R) in cardiomyocytes. Ca uptake and
      release of the SR vesicles was determined by use of Ca and the Millipore
      filtration technique. Western blotting analysis was used to detect calreticulin
      expression and activity of p38 MAPK. Hypoxic preconditioning induced calreticulin
      upregulation and attenuated H/R injury in neonatal cardiomyocytes and myocardial
      ischemia injury by increasing calcium uptake and reducing calcium release in SR.
      Hearts from the HPC group were more resistant to sustained ischemia and had much
      stronger phosphorylation of p38 MAPK than sham operation. Inhibition of p38 MAPK
      with SB202190 (a selective p38 MAPK inhibitor) abolished the calreticulin
      upregulation and cardioprotection by HPC. Hypoxic preconditioning upregulates
      calreticulin expression through a p38 MAPK signaling pathway and protects
      cardiomyocytes from H/R (and ischemia) injury.

PMID- 17438465
TI  - Glucocorticoids do not protect against the lethal effects of experimental
      heatstroke in baboons.
AB  - The mortality and neurological morbidity in heatstroke have been attributed to
      the host's inflammatory responses to heat stress, suggesting that anti
      inflammatory therapy may improve outcome. We tested the hypothesis that a high
      dose of dexamethasone protects baboons against the lethal effects of heatstroke.
      Ten anesthetized baboons (Papio hamadryas) were assigned randomly to
      dexamethasone (n = 5) or control group (n = 5). Dexamethasone (2 mg/kg i.v.) was
      administered in four divided doses every 6 h starting immediately before heat
      stress and continuing during cooling. All animals were heat-stressed in a
      prewarmed neonatal incubator at 44 degrees C to 47 degrees C until systolic blood
      pressure fell less than 90 mmHg and then cooled passively at the ambient
      temperature. Mortality and neurological morbidity were noted, and biochemical
      markers of tissue injury/organ dysfunction were determined. Circulating
      interleukin (IL) 6 and complement components (C3 and C4) were measured
      sequentially. All heat-stressed animals had systemic inflammation indicated by
      increased plasma IL-6 and decreased C3 and C4 levels. Dexamethasone attenuated
      the complement system activation and maintained a higher plasma concentration of
      IL-6, with a significant augmentation of arterial blood pressure. Dexamethasone
      did not prevent the occurrence of severe heatstroke but unexpectedly aggravated
      significantly the tissue injury and multiorgan system dysfunction. Two animals
      (40%) in the control group and one in the steroid group survived (P > 0.05).
      Dexamethasone failed to protect the baboons from the lethal effects of
      heatstroke. These results do not support clinical testing of corticosteroids as
      beneficial in preventive or therapeutic strategies for the treatment of
      heatstroke in humans.

PMID- 17438466
TI  - Effects of positive end-expiratory pressure in an experimental model of acute
      myocardial infarct in wistar rats.
AB  - Our purpose in this study was to access the pulmonary effects of mechanical
      ventilation with positive end-expiratory pressure (PEEP; 10 cmH2O) or without
      PEEP (zero PEEP-ZEEP) in a rat model of acute myocardial infarction that resulted
      in hypotension but not in pulmonary congestion. METHODS: Wistar rats were
      anesthetized (1.5% isoflurane) and myocardial infarct was induced by ligature of
      the anterior interventricular coronary artery. Rats with myocardial infarct were
      compared with sham-operated (Sham) and closed thorax groups. RESULTS AND
      CONCLUSION: There was a significant decrease in MAP in the acute myocardial
      infarct group (92.5 +/- 4.2 mmHg) when compared with closed chest group (113.0 +/
      4.4 mmHg). There was no significant difference between acute myocardial infarct
      and Sham groups in PEEP or ZEEP. Mechanical ventilation for 120 min resulted in a
      significant increase in respiratory system elastance in the groups ventilated
      with ZEEP (2.59 +/- 0.17 and 2.32 +/- 0.17 cmH2O.mL, Sham and acute myocardial
      infarct groups, respectively). This effect of mechanical ventilation was not
      observed in the presence of PEEP in both groups. There was no significant
      increase in the amount of perivascular pulmonary edema measured in all groups
      studied. Mean airspace linear intercept and lung tissue distortion index also did
      not show statistically significant difference between Sham and acute myocardial
      infarct groups. We conclude that in this experimental model of acute myocardial
      infarct (12.4 +/- 4.1% area of necrotic tissue and 26.4 +/- 4.0% area of ischemic
      tissue), there was a protective pulmonary effect of PEEP.

PMID- 17438467
TI  - Serum metal ion exposure after total knee arthroplasty.
AB  - All metal implants release metal ions because of corrosion. This has been studied
      and debated, especially in metal-on-metal total hip arthroplasties. Total knee
      arthroplasty implants have large metal surface areas and therefore substantial
      potential for corrosion. We determined changes in serum levels of metal ions in
      41 patients after cemented unconstrained total knee arthroplasty without patellar
      resurfacing, 18 with unilateral total knee arthroplasty (median, 66 months after
      surgery) and 23 patients with bilateral total knee arthroplasties (75 and 50
      months after first and second surgeries, respectively). Serum concentrations of
      chromium, cobalt, and molybdenum were analyzed and related to the number of total
      knee arthroplasties and compared with those of 130 control patients without
      implants. The median chromium, cobalt, and molybdenum concentrations were 0.92,
      3.28, and 2.55 microg/L, respectively, in the unilateral total knee arthroplasty
      sample and 0.98, 4.28, and 2.40 microg/L, respectively, in the bilateral total
      knee arthroplasty sample. We observed no difference between the serum levels in
      patients with unilateral and bilateral arthroplasties, but the serum levels of
      chromium and cobalt of both study groups were greater than those of the control
      group (less than 0.25 microg/L). The patients who had total knee arthroplasty had
      molybdenum profiles that were similar to those of the control group (median, 2.11
      microg/L).

PMID- 17438468
TI  - Tuberculosis of the spine: a review.
AB  - We analyzed 124 papers published in the English language literature to define the
      indications and timing of surgery in spinal TB and to evaluate the outcome of
      various surgical procedures for kyphosis and neural outcome. Surgery in spinal
      tuberculosis is indicated for diagnostic dilemma, neural complications, and
      prevention of kyphosis progression. Up to 76% canal encroachment is compatible
      with a normal neurologic state as the spinal cord tolerates gradually developing
      compression. Patients with relatively preserved cord size, but with
      edema/myelitis and predominantly fluid compression on MRI respond well to
      nonoperative treatment. We believe patients with extradural compression by
      granulation tissue with little fluid component compressing or constricting the
      cord circumferentially with cord edema/myelitis or myelomalacia need early
      surgical decompression. Transthoracic transpleural anterior decompression and
      extrapleural anterolateral decompression have similar results in the dorsal
      spine. Instrumented stabilization helps prevent graft-related complications when
      postdebridement defects exceed two disc spaces (4-5 cm). Progression of kyphosis
      may occur in a short-segment disease despite instrumented stabilization. Its
      outcome in a long-segment disease needs observation. The correction of healed
      kyphosis requires multistage surgery and is fraught with complications.
      Prospective studies are needed to define surgical approach, steps, stages,
      problems, and obstacles to correct severe kyphosis in spinal TB.

PMID- 17438469
TI  - Surgical debridement and parenteral antibiotics in infected revision total knee
      arthroplasty.
AB  - Whether surgical debridement and parenteral antibiotics with prosthesis retention
      for infected revision TKA eradicates infection is not well established. We sought
      to determine the prevalence of reinfection. Between 1992 and 2003, we
      prospectively followed 40 consecutive patients with deep infection after revision
      TKA. These patients had no prosthesis loosening or malalignment. Using the
      classification of Tsukayama et al, 10, 20, and 10 patients had Types I (acute
      postoperative), II (late chronic), and III (acute hematogenous) infections,
      respectively. All had surgical debridement and parenteral antibiotics with
      retention of their existing prostheses. The patients were followed for a minimum
      of 3 years (range, 36-143 months). Successful implant salvage was achieved in 12
      of the 40 patients (30%). However, likelihood of success depended on the type of
      infection: patients with Type I infections (seven of 10) and patients with Type
      III infections (five of 10) retained their prostheses more often than patients
      with Type II infections (zero of 20). We recommend early debridement and
      retention of the prosthesis with Type I or Type III infections in revised TKAs,
      but primary removal for Type II infections.

PMID- 17438470
TI  - Intramuscular hemangioma: recurrence risk related to surgical margins.
AB  - The best treatment for intramuscular hemangiomas is unclear in part because the
      outcome is variable, with recurrence rates ranging from 18% to 61%. This variance
      is due to deficiencies in previous reports such as an inadequate population size,
      lack of life table analyses, lack of uniform pathologic criteria, and loose or
      absent definition of surgical margins. Our goal was to address these deficiencies
      and support or refute previous results. We identified 110 patients between 1981
      and 2005. There were 48 males and 62 females with an average age of 22 years at
      the time of consult. Kaplan-Meier analysis showed 76% of patients managed
      initially without excision were surgery-free at 2 years and 66% at 5 years. For
      patients treated with surgery, 86% and 73% were recurrence free at 2 and 5 years,
      respectively. There were substantial differences in local recurrence when
      stratified by margin: 93% of patients were recurrence free at 5 years when the
      excision was marginal and wide, 65% when intralesional without any gross
      remaining tumor, and 33% when intralesional with gross remaining tumor. Surgical
      margins and tumor size were the only identified risk factors for recurrence.

PMID- 17438471
TI  - Reconstruction of noncontained proximal tibial defects with divergent screws and
      cement.
AB  - Postoperative fracture is a well described complication following curettage and
      cementation of aggressive benign bone tumors. We asked whether: (1) the addition
      of diverging screws that engage the opposite cortex increase the strength and
      rigidity of the construct in the proximal tibia compared with (a) cement alone
      and (b) would cement with intramedullary Steinmann pins; and (2) the modes of
      failure be different for those constructs. The average load to failure for tibias
      reconstructed with cement augmented with diverging screws (6321 +/- 681 N) was
      higher than for tibias reconstructed with cement alone (2343 +/- 222 N). The
      average load to failure for tibias reconstructed with cement augmented with
      diverging screws (6885 +/- 445 N) was higher than for tibias reconstructed with
      cement and intramedullary Steinmann pins (5218 +/- 941 N). Furthermore,
      constructs with cement augmented with diverging screws were less likely to fail
      by an intraarticular fracture than other types of constructs. Our data support
      the use of diverging screws that engage the opposite cortex to augment the
      strength of the construct when using acrylic cement to fill noncontained defects
      after curettage of the proximal tibia. This more stable, stronger construct might
      allow earlier mobilization and rehabilitation after curettage, with a decreased
      risk of fracture.

PMID- 17438472
TI  - Radiotherapy to bone has utility in multifocal metastatic renal carcinoma.
AB  - Renal cell carcinoma metastases to bone are classically considered
      radioresistant. We reviewed 28 patients who underwent irradiation for metastatic
      renal cell carcinomas to bone to test the hypothesis that irradiation of renal
      metastases to bone provides adequate palliation in carefully selected patients.
      Metastases were multifocal in all patients. All patients were followed until
      death. Overall, 36 index radiotherapy treatments were given as palliative initial
      treatment for 36 osseous metastatic sites. Twenty-five of 36 sites (69.5%) had no
      subsequent radiotherapy. Eight sites (22.2%) underwent repeat radiotherapy at a
      mean 28.9 weeks after treatment. Two (5.6%) additional sites underwent surgery at
      the site at an average 74 weeks later, and a pathologic fracture occurred at one
      (2.8%) site 3 weeks after irradiation. Overall, 33 of 36 (91.7%) sites had only
      radiotherapy as their source of palliation. Median times to return to
      pretreatment pain and functional levels, however, were 2 months and 1 month,
      respectively. Radiotherapy to osseous sites appears to control pain for the short
      term and generally prevents fractures and avoids the need for surgery in renal
      cell carcinoma patients with multiple bone metastases.

PMID- 17438473
TI  - Web-based resources for orthopaedic oncology information.
AB  - With the increasing reliance of patients on the Internet for medical information,
      accessible and comprehensive resources are important. We retrieved orthopaedic
      oncology information sites for patients and professionals from three search
      engines. We evaluated 70 sites with two raters, plus an additional nine sites
      suggested by Musculoskeletal Tumor Society members. Only five patient sites and
      seven provider sites met our inclusion criteria. Of these, only one of each was
      peer-reviewed. In contrast to other disease states such as melanoma or bladder
      cancer, there are relatively few orthopaedic oncology sites available on the Web.

PMID- 17438474
TI  - Indeterminate pulmonary nodules in patients with sarcoma affect survival.
AB  - We prospectively studied 331 sarcoma patients treated between April 1999 and
      December 2004 to see if small, indeterminate pulmonary nodules are of prognostic
      significance. Seventy-one (21%) had indeterminate pulmonary nodules on initial
      spiral CCT. Twenty of 71 (28%) patients with indeterminate nodules progressed
      with metastatic disease. Metastatic disease developed in 18/20 (90%) in the area
      of the original indeterminate nodule. The presence of tiny (<5 mm) indeterminate
      nodules was not a prognostic variable, however, the presence of nodules > or =5
      mm was associated with worse 3 year disease-free survival compared to those with
      no nodules or tiny nodules (81% versus 49%) but better than those with definite
      metastatic disease at presentation (49% versus 5%). Because patients with
      pulmonary nodules > or =5 mm are at increased risk for metastatic disease
      compared to patients with normal CCT or those with <5 mm nodules but better
      survival than patients with Stage IV disease, we believe a new staging system of
      these patients should be considered and recommend careful followup.

PMID- 17438475
TI  - Direct internal kyphectomy for severe angular tuberculous kyphosis.
AB  - We describe a direct internal kyphectomy through a modified costotransversectomy,
      an extrapleural approach to the kyphus that does not jeopardize already
      compromised pulmonary function. A curved longitudinal incision is made 6 to 8 cm
      lateral to the midline. The posterior 5 cm of the two to three crowded ribs at
      the apex are resected. The segmental intercostal nerves are preserved as a guide
      into the spinal canal. Two to three pedicles at the apex are resected. The pleura
      are elevated with blunt dissection leading to the internal kyphus. Removal of the
      posterior half of the collapsed vertebrae is performed with a high-speed burr;
      the posterior walls are removed last to avoid forward migration of the dural sac
      as the decompression progresses. Cortical strut grafting is then performed as far
      anteriorly as the exposure permits. We treated five patients with paraparesis of
      healed disease with this approach. Preoperatively the mean kyphosis was 114
      degrees. Neurological improvement was obtained in two patients. At a mean
      followup of 5 years, solid anterior fusion was achieved in four patients. One
      patient died 5 months after surgery because of chest infection.

PMID- 17438476
TI  - Painful tibial lesion in a 16-year-old girl.

PMID- 17438477
TI  - Coaxial extendible knee equalizes limb length in children with osteogenic
      sarcoma.
AB  - We assessed our ability to achieve limb length equality (LLE) in children
      following limb-sparing surgery for distal femur osteogenic sarcoma using coaxial
      extendible prostheses in 12 children, averaging 11.6 years old at the time of
      tumor resection (range, 5.9-15.5 years). All but one child achieved clinical limb
      length equality. There were 23 extensions, averaging 3.8 extensions per patient
      (range, 1-5), by an average 13 mm per extension and an average total extension of
      49.3 mm per patient extended. Eight children underwent revision surgery after an
      average of 45.1 months (range, 3-115 months). Aseptic loosening occurred more
      frequently among children with greater femoral diameter growth. The overall
      prosthetic survival was 60% at 3 years and 35% at 5 years. The survival until
      aseptic loosening at 3 and 5 years was 85% and 45%, respectively. Press-fit
      components survived longer than cemented stems. None of the devices loosened. At
      skeletal maturity the MSTS functional scores averaged 25. Using a coaxial
      extendible implant, we efficiently achieved LLE in this population. Prosthetic
      revision was needed frequently. Younger age and longer resection percentages were
      associated with shorter prosthetic survival and higher revision/aseptic loosening
      rates. Femoral diameter growth may contribute to loosening. Early experience with
      this extendible implant is promising.

PMID- 17438478
TI  - Discontinuation and modification of highly active antiretroviral therapy in HIV
      infected Ugandans: prevalence and associated factors.
AB  - BACKGROUND: Data on discontinuation and modification of highly active
      antiretroviral therapy (HAART) are scarce among sub-Saharan African populations.
      We sought to estimate the prevalence and to identify factors associated with
      these phenomena in our resource-limited setting. METHODS: Patients were recruited
      into this cross-sectional study from 2 treatment centers in Kampala, Uganda.
      Discontinuation and modification were assessed by self-report using
      semistructured quantitative and unstructured qualitative interviews.
      Discontinuation was defined as the simultaneous stopping of all antiretrovirals
      for at least 1 month, and modification as the changing of at least 1
      antiretroviral used in an initial HAART regimen. Factors independently associated
      with each outcome were assessed using multivariate logistic regression. RESULTS:
      Of 686 subjects evaluated, 94 (13.7%) had ever discontinued therapy, whereas 175
      (25.5%) had ever modified their regimen. The median CD4 count was 175
      (interquartile range: 66-297) cells/microL. Factors associated with
      discontinuation were HAART experience before starting the current regimen (odds
      ratio [OR] = 3.70, 95% confidence interval [CI]: 2.13 to 6.25), use of
      alternative medicines (OR = 2.18, 95% CI: 1.06 to 4.47), hospitalization (OR =
      2.36, 95% CI: 1.32 to 4.20), and 1 year or less on HAART (OR = 11.11, 95% CI:
      5.00 to 25.00). Modification was associated with more than 3 months' duration on
      HAART (OR = 3.13, 95% CI: 1.16 to 8.33) and being unmarried (OR = 1.64, 95% CI:
      1.02 to 2.70). CONCLUSIONS: The proportions of discontinuation and modification
      of antiretroviral therapy (ART) observed in our resource-poor setting pose a
      challenge to the limited treatment options presently available. Drug cost as a
      major reason for discontinuation of HAART has major implications for ART programs
      that charge fees in resource-limited settings.

PMID- 17438479
TI  - Field adherence to highly active antiretroviral therapy in HIV-infected adults in
      Abidjan, Cote d'Ivoire.
AB  - OBJECTIVES: To estimate adherence to highly active antiretroviral therapy (HAART)
      and its determinants in HIV-infected adults followed in field conditions in
      Abidjan. METHODS: A standardized questionnaire was administered to all
      consecutive adults on HAART who attended 3 urban HIV outpatient clinics. Patients
      were asked to self-report their pill intake during the previous 7 days, and, when
      necessary, to explain the reason(s) why they missed at least 1 intake. The
      adherence rate was estimated as the number of pills actually taken divided by the
      number of pills that should have been taken. The association of incomplete
      adherence (adherence rate<90%) with patients' characteristics was studied using
      multivariate logistic regression. RESULTS: Three hundred eight patients
      (male/female ratio: 1:1, mean time on HAART: 22 months) were interviewed. The
      median self-reported adherence rate was 78% (interquartile range: 65%-90%), with
      76% of patients considered as incompletely adherent (adherence rate<90%). The
      most frequent self-reported reasons for missing at least 1 intake were an
      antiretroviral drug being out of stock in the clinic pharmacy (28%), the fear of
      drug side effects (27%), the impossibility of paying the drug's price (20%), and
      the intervention of traditional practitioners (18%). The only variables
      significantly independently associated with incomplete adherence were a school
      level>or=secondary (odds ratio [OR]=1.88; P=0.03) and the absence of a patient's
      long-term formal commitment to adhere to HAART (OR=3.08; P=0.01). CONCLUSIONS:
      These data illustrate the difficulty in obtaining high levels of adherence in
      field conditions in Abidjan. Sustainable access to treatment should be promoted
      by combating access barriers such as running out of drugs and costs that are too
      high.

PMID- 17438480
TI  - Transmission rates in consecutive pregnancies exposed to single-dose nevirapine
      in Soweto, South Africa and Abidjan, Cote d'Ivoire.
AB  - BACKGROUND: Large numbers of women receive single-dose nevirapine (sdNVP) to
      prevent mother-to-child transmission (MTCT) of HIV; over time, an increasing
      proportion will return to prevention of MTCT programs for a second pregnancy.
      Because sdNVP selects resistance in a high percentage of women, we compared the
      effectiveness of sdNVP in preventing peripartum MTCT in successive pregnancies.
      METHODS: Prospective cohorts were recruited from MTCT programs in South Africa
      and Cote d'Ivoire. HIV-1-infected women and their infants exposed to sdNVP in 2
      consecutive pregnancies-used alone or with zidovudine (ZDV) or ZDV plus
      lamivudine-were included. RESULTS: The median age of women at their initial
      exposure to sdNVP in Soweto (n = 120) and Abidjan (n = 41) was 26 (interquartile
      range [IQR]: 22-29) years and 28 (IQR: 24-31) years, respectively, and their
      median delivery interval was 21 (IQR: 15-29) months and 26 (IQR: 20-32) months,
      respectively. Transmission rates in Soweto and in Abidjan were 11.1% and 13.2%
      for the first pregnancy and 11.1% and 5.4% for the second pregnancy (P = 1.000
      and P = 0.449 for Soweto and Abidjan, respectively, in unpaired analysis).
      CONCLUSION: This analysis suggests that the effectiveness of sdNVP when used in
      successive pregnancies is probably not impaired, possibly because viral
      resistance selected by prior exposure to sdNVP may wane with time.

PMID- 17438481
TI  - Effects of insulin on hepatic inflammation induced by ethanol and burn injury in
      a murine model of critical illness.
AB  - In recent, landmark clinical trials, insulin to maintain euglycemia in critically
      ill patients improved clinical outcomes, including decreased all-cause mortality.
      Novel antiinflammatory effects of insulin have recently been described. Thermal
      injury is an excellent model of critical illness. The addition of ethanol to the
      model is of great clinical relevance because nearly 50% of the patients admitted
      to hospitals for burn injuries have ethanol in their circulation. Utilizing a
      murine model of critical illness (ethanol and skin burn), we tested the
      hypothesis that insulin treatment in ethanol-exposed, burn-injured mice reduced
      hepatic inflammation, a potential mechanism for the benefit of insulin. Adult
      male C57BL/6 mice were given a single intraperitoneal injection of ethanol or
      saline, were given a 15% total body full-thickness skin burn, or were sham-burned
      and killed 24 hours later. In each group, half the animals were given
      subcutaneous injections of the long-lasting basal insulin glargine; the other
      half, the appropriate vehicle. Hepatic inflammatory markers, including
      polymorphonuclear infiltration, a chemokine, an important adhesion molecule,
      proinflammatory cytokines, and nuclear factor kappaB, were measured, and all were
      increased by ethanol and/or burn. These increases were prevented by insulin. An
      antiinflammatory cytokine was reduced by ethanol and/or burn. Insulin prevented
      this decrease. Thus, insulin has a substantial antiinflammatory effect, and this
      may underlie its dramatic clinical benefit in critical illness.

PMID- 17438482
TI  - Inhibition of rho-kinase impairs fibroblast stress fiber formation, confluence,
      and contractility in vitro.
AB  - Rho kinase is an enzyme that has been implicated in pathological wound healing.
      In our study, we aimed to characterize the dosages of Y-27632 (a competitive
      inhibitor of rho kinase) at which fibroblast stress fiber formation is inhibited,
      to determine the effect of Y-27632 on fibroblast confluence, and to determine the
      effect of varying concentrations of Y-27632 on fibroblast-mediated gel
      contraction. First, 3T3 fibroblasts were exposed to various concentrations of Y
      27632, and stress fiber dissolution was assessed with immunofluorescence. Next,
      10 microM Y-27632 was applied to 3T3 fibroblast monolayer cultures immediately
      after plating and at 8 hours after plating to determine the effect on fibroblast
      confluence. Finally, a three-dimensional model was used to assess the effect of Y
      27632 on gel contraction. Increasing doses of Y-27632 resulted in a dose
      dependent increase in stress fiber dissolution as well as a dose-dependent
      inhibition of gel contraction. Median number of days to confluence were 3, 5, and
      6 after no, immediate, and delayed incubation with Y-27632, respectively (P <
      .05). Our results further characterize the dosages at which Y-27632 may be most
      effective in the modulation of wound contraction in burn patients. In addition,
      our confluence study suggests that patients need not necessarily be pretreated
      with Y-27632.

PMID- 17438483
TI  - Initial reconstruction of sustained neck and facial burns.
AB  - Approximately 50% of burn injuries involve the neck and head region. Because both
      appearance and function must be taken into account with burns of this area,
      several consecutive reconstructions will be performed. With a focus on improving
      outcome after burn injury, we underline the method of grafting as a very
      important element in primary surgery. With our special excision and grafting
      technique, we aim to achieve a reconstruction that deals with mobility and
      aesthetics. Consequently, necessary reconstructive procedures may be fewer and of
      less magnitude. We describe this surgical technique in detail. In this study we
      surgically treated 39 patients with sustained facial and neck burns. For 22
      patients this surgical treatment circumvented the need to perform any secondary
      reconstructions. The proposed treatment involves a special grafting technique
      after pretreatment with a topical agent in combination with early pressure
      therapy.

PMID- 17438485
TI  - Incidence of hepatic dysfunction is equivalent in burn patients receiving
      oxandrolone and controls.
AB  - Oxandrolone has been shown to improve lean muscle mass in patients with burns.
      Hepatic dysfunction is a known side effect of treatment with oxandrolone. The
      purpose of this study was to examine the incidence of hepatic dysfunction in our
      series of burn patients receiving oxandrolone. Fourteen patients who received
      oxandrolone (5 mg, n = 8; 10 mg, n = 6) were identified from our prospectively
      collected burn database. The records of 61 control patients also were reviewed.
      Demographics such as age, comorbidities, and burn size were recorded. The
      incidence of hepatic dysfunction was determined by the presence of abnormal liver
      function tests. The study and control groups were similar in age and burn size.
      Two of the eight (25%) oxandrolone patients receiving 5 mg and four of the six
      (67%) oxandrolone patients receiving 10 mg had evidence of hepatic dysfunction.
      Twenty six of the 61 (43%) control patients had evidence of hepatic dysfunction
      (P = NS). There appears no significant increased incidence of hepatic dysfunction
      in burn patients who received oxandrolone compared to those who did not.

PMID- 17438486
TI  - Management of scalp toxic epidermal necrolysis and cranial osteomyelitis with
      serratus anterior myocutaneous pedicle flap: a case report.
AB  - The aim of this report is to describe the management of scalp toxic epidermal
      necrolysis (TEN) and cranial osteomyelitis complicating malignant glioma therapy.
      A 21-year-old man developed TEN while being radiated and receiving antineoplastic
      and anticonvulsant therapies for a malignant intracranial glioma. The strategy
      used to manage the above situation included withdrawal of the medications causing
      TEN, meticulous dermatological wound care, resection of residual glioma,
      debridement of scalp and bone, and reconstruction of the scalp and calvarial
      defect with a myocutaneous vascularized free flap. The scalp wounds have healed
      completely in a cosmetically acceptable fashion and the patient remains free of
      tumor recurrence approximately 18 months after surgery, having completed a course
      of systemic chemotherapy. TEN may complicate the use of anticonvulsant and
      antineoplastic medications in malignant glioma patients. Withdrawal of the
      offending agent and immune suppressant medications, skin care and infection
      control, tumor resection to diminish steroid use, and reconstruction of scalp and
      calvarial defects with a vascularized myocutaneous flap facilitate wound healing
      and permit resumption of antineoplastic therapies.

PMID- 17438487
TI  - Carbon monoxide-induced status epilepticus in an adult.
AB  - There have been numerous reports documenting the occurrence of self-limiting
      seizures after carbon monoxide poisoning in the pediatric population. However,
      the literature has been less informative concerning the adult population. This
      report documents a 70-year-old female who was found to be in nonconvulsive status
      epilepticus after acute carbon monoxide poisoning with a carboxyhemoglobin level
      of 35%. To our knowledge, this is the first report of acute carbon monoxide
      poisoning inducing nonconvulsive status epilepticus in an adult. This report adds
      to the growing body of knowledge concerning acute carbon monoxide poisoning by
      further exploring the very complex symptomatology that presents in the adult
      population.

PMID- 17438488
TI  - The reported effects of bullying on burn-surviving children.
AB  - There is a trend of increasing childhood aggression in America, which has been
      tied to bullying. Although there is growing research concerning bullying in the
      general pediatric population, there are limited data on bullying and its effects
      on children with disfigurements and physical limitations. This study was
      conducted to assess burned children's experience with bullying. A pretest was
      administered regarding experience with bullying and teasing. A curriculum
      regarding bullying, which incorporated the Harry Potter and the Sorcerer's Stone
      movie, was presented. After reviewing bullying depicted in the film and
      participating in a class regarding bullying, children were invited to complete a
      survey regarding their experience with bullying. A total of 61% of these children
      reported being bullied at school; 25% reported experiencing headaches or
      stomachaches due to bullying, and 12% reported staying home from school. Nearly
      25% reported bullying as a big problem. Of those with visible scars (55%), a full
      68% reported bullying as a problem, versus 54% with hidden scars (P < .05).
      However, those with visible scars were no more likely to tell an adult (54%) than
      those without (56%). Children were much more willing to disclose personal
      bullying experiences after participating in the class (57%) than before (45%) (P
      < .01). This study revealed that bullying impacts many burn-injured children and
      has negative effects on their physical and mental well-being. Many children (with
      visible or hidden scars) did not seek adult intervention for the problem.
      Participation in a bullying course appears to give children a forum that
      increases their willingness to disclose personal bullying experiences and can
      provide them with prevention information and a safe place to seek help.

PMID- 17438489
TI  - The phenomenon of "fluid creep" in acute burn resuscitation.
AB  - Several reports have documented that modern burn patients receive far more
      resuscitation fluid than predicted by the Parkland formula-a phenomenon termed
      "fluid creep." This article reviews the incidence, consequences, and possible
      etiologies of fluid creep in modern practice and uses this information to propose
      some therapeutic strategies to reduce or eliminate excessive fluid resuscitation
      in burn care. A literature review was performed of historical references that
      form the foundation of modern fluid resuscitation, as well as reports of fluid
      creep and its consequences. The original Parkland formula required a 24-hour
      volume of 4 ml/kg/%TBSA lactated Ringer's solution followed by an infusion of 0.3
      0.5 ml/kg/ %TBSA plasma. Modern iterations of this formula have omitted the
      colloid bolus. Numerous exceptions to the formula have been noted, most
      consistently patients with inhalation injuries. In contrast, recent reports
      document greatly increased fluid requirements in unselected patients, which seems
      to consist largely of progressive edema formation in unburned areas, increasing
      after the first 8 hours post-burn. This has been linked to occurrence of the
      abdominal compartment syndrome and other serious complications. Strategies to
      reduce fluid creep include the avoidance of early overresuscitation, use of
      colloid as a routine component of resuscitation or for "rescue," and adherence to
      protocols for fluid resuscitation. Fluid creep is a significant problem in modern
      burn care. Review of original investigations of burn shock, coupled with modern
      reports of fluid creep, suggests several mechanisms by which this problem can be
      controlled. Prospective trials of these therapies are needed to confirm their
      effectiveness.

PMID- 17438490
TI  - Intravenous colistin for the treatment of multi-drug resistant, gram-negative
      infection in the pediatric burn population.
AB  - The rising incidence of multi-drug resistant (MDR) gram-negative infections in
      the intensive care unit (ICU) continues to challenge clinicians and has resulted
      in reemergence of the glycopeptide antibiotic colistin. Over the past 11 years,
      14 patients at a tertiary pediatric burn center were treated with colistin for
      gram-negative infections resistant to all tested antibiotics. This study reviews
      the safety of such treatment and the outcome for this cohort of patients. All
      hospitalized patients treated with intravenous colistin between 1990 and 2005
      were identified. A retrospective chart review was performed for each patient.
      Demographic data, along with information regarding the type and severity of
      injury, were collected. Data with respect to microbiology, renal status, and
      neurological events were also noted. Over an 11-year period, we identified 14
      children infected with pan-resistant gram-negative organisms requiring 16 courses
      of colistin. Two children (14.3%) developed significant rises in serum creatinine
      concentration; however, no child required renal replacement therapy or developed
      neurologic complications attributable to colistin. Favorable response rate was
      78.6% (11/14), and overall mortality was 14.3% (2/14); both deaths were
      attributed to sepsis. In our experience with 14 children treated with intravenous
      colistin, two developed a significant elevation in serum creatinine concentration
      during the course of therapy and neurotoxicity was not reported. Colistin should
      be dispensed with great caution, but it appears to have an acceptable safety
      profile in children and may be used in select cases of infection with highly
      resistant gram-negative organisms.

PMID- 17438491
TI  - Skin grafting impairs postsynaptic cutaneous vasodilator and sweating responses.
AB  - This study tested the hypothesis that postsynaptic cutaneous vascular responses
      to endothelial-dependent and -independent vasodilators, as well as sweat gland
      function, are impaired in split-thickness grafted skin 5 to 9 months after
      surgery. Intradermal microdialysis membranes were placed in grafted and adjacent
      control skin, thereby allowing local delivery of the endothelial-dependent
      vasodilator, acetylcholine (ACh; 1 x 10(-7) to 1 x 10(-1) M at 10-fold
      increments) and the endothelial-independent nitric oxide donor, sodium
      nitroprusside (SNP; 5 x 10(-8) to 5 x 10(-2) M at 10-fold increments). Skin blood
      flow and sweat rate were simultaneously assessed over the semipermeable portion
      of the membrane. Cutaneous vascular conductance (CVC) was calculated from the
      ratio of laser Doppler-derived skin blood flow to mean arterial blood pressure.
      deltaCVC responses from baseline to these drugs were modeled via nonlinear
      regression curve fitting to identify the dose of ACh and SNP causing 50% of the
      maximal vasodilator response (EC50). A rightward shift in the CVC dose response
      curve for ACh was observed in grafted (EC50 = -2.61 +/- 0.44 log M) compared to
      adjacent control skin (EC50 = -3.34 +/- 0.46 log M; P = .003), whereas the mean
      EC50 for SNP was similar between grafted (EC50 = -4.21 +/- 0.94 log M) and
      adjacent control skin (EC50 = -3.87 +/- 0.65 log M; P = 0.332). Only minimal
      sweating to exogenous ACh was observed in grafted skin whereas normal sweating
      was observed in control skin. Increased EC50 and decreased maximal CVC responses
      to the exogenous administration of ACh suggest impairment of endothelial
      dependent cutaneous vasodilator responses in grafted skin 5 to 9 months after
      surgery. Greatly attenuated sweating responses to ACh suggests either abnormal or
      an absence of functional sweat glands in the grafted skin.

PMID- 17438492
TI  - Impaired cutaneous vasodilation and sweating in grafted skin during whole-body
      heating.
AB  - The aim of this investigation was to identify the consequences of skin grafting
      on cutaneous vasodilation and sweating in split-thickness grafted skin during
      indirect whole-body heating 5 to 9 months after surgery. In addition,
      thermoregulatory function was examined at donor skin sites on a separate day.
      Skin blood flow and sweat rate (SR) were assessed from both grafted (n = 14) or
      donor skin (n = 11) and compared with the respective adjacent control skin during
      indirect whole-body heating. Cutaneous vascular conductance (CVC) was calculated
      from the ratio of skin blood flow (arbitrary units; au) to mean arterial
      pressure. Whole-body heating significantly increased internal temperature (37.0
      +/- 0.1 degrees C to 37.8 +/- 0.1 degrees C; P < .05). Cutaneous vasodilation
      (ie, the increase in CVC from baseline, deltaCVC) during whole-body heating was
      significantly attenuated in grafted skin (deltaCVC = 0.14 +/- 0.15 au/mm Hg)
      compared with adjacent control skin (deltaCVC = 0.84 +/- 0.11 au/mm Hg; P < .05).
      Increases in sweat rate (deltaSR) were also significantly lower in grafted skin
      (deltaSR = 0.08 +/- 0.08 mg/cm2/min) compared with adjacent control skin (deltaSR
      = 1.16 +/- 0.20 mg/ cm2/min; P < .05). Cutaneous vasodilation and sweating during
      heating were not significantly different between donor sites (deltaCVC = 0.71 +/-
      0.19 au/mm Hg; deltaSR = 1.04 +/- 0.15 mg/cm2/min) and adjacent control skin
      (deltaCVC = 0.50 +/- 0.10 au/mm Hg; deltaSR = 0.83 +/- 0.17 mg/cm2/min). Greatly
      attenuated or absence of cutaneous vasodilation and sweating suggests impairment
      of thermoregulatory function in grafted skin, thereby, diminishing the
      contribution of this skin to overall temperature control during a heat stress.

PMID- 17438493
TI  - Epidemiology of hospitalized burn patients in Shandong Province: 2001-2005.
AB  - The aim of the article was to describe the epidemiology of burn injuries
      requiring hospitalization at Shandong Provincial Hospital and to provide
      information necessary for the design and implementation of effective prevention
      programs. The records of patients with burn injury admitted to our burn unit over
      a 5-year period (1 January 2001 to 31 December 2005) were reviewed. Medical
      record review provided basic demographic information and details on the extent of
      injury, time of day burns occurred, month of admission, cause of burn, accident
      site, first aid, number of operations, length of hospital stay, and mortality.
      There was no trend in annual admissions. The male-to-female ratio was 3:1. The
      age distribution of burn patients showed peaks occurring at the age groups of 0
      to 10 and 20 to 30 years. Over the course of a day, burn injuries occurred most
      frequently from 1700 to 1900 hours. Scalds accounted for 45.23% (502) of the 1110
      patients, and flame burns accounted for 42.33% (471). Only 29% of all patients
      received proper first aid with cool water or burn cream. The average length of
      hospital stay was 22 days. Children under 10 years and adults between 20 and 30
      years of age are the most susceptible populations, and first aid is performed
      poorly in Shandong Province. Burn prevention and first aid education campaigns
      should be launched to encourage safe lifestyle and work habits.

PMID- 17438494
TI  - Patrimonie de Docteur Baux--Baux scores >> 100 gleaned from 170,791 admissions: a
      glimmer from the National Burn Repository.

PMID- 17438495
TI  - Length of hospitalization: an important parameter for burned patients.

PMID- 17438496
TI  - A dangerous sequele of frostbite: third-degree ear burn.

PMID- 17438497
TI  - Assessment of cooling on an acute scald burn injury in a porcine model.
AB  - The current Australian and New Zealand Burn Association (ANZBA) recommended Burns
      First Aid Treatment is place the burn under cool running water for 20 minutes.
      Wet towels and water spray also have been used frequently. No scientific data
      exist to compare the effectiveness of these methods of cooling. This study sought
      to determine experimental evidence for current Burns First Aid Treatment
      recommendations and the optimal mode of cooling. Four partial-thickness scald
      burn injuries were induced in 10 piglets each. First aid was then applied for 20
      minutes via cool running water, wet towels, or water spray, with no treatment as
      a control. At day 1 and day 9, biopsies and clinical photographs were assessed in
      a blinded manner. The control group showed worsening or no change of depth over
      the course of 9 days. The outcomes with wet towels and water spray were variable.
      Cool running water consistently demonstrated improvement in wound recovery over
      the course of 9 days (P < .05). This study demonstrated that cool running water
      appeared the most effective first aid for an acute scald burn wound in a porcine
      model compared with wet towels and water spray.

PMID- 17438498
TI  - The microvasculature in cutaneous wound healing in the female red Duroc pig is
      similar to that in human hypertrophic scars and different from that in the female
      Yorkshire pig.
AB  - The female red Duroc pig has been found to be a promising model of hypertrophic
      scarring. The female Yorkshire pig has been demonstrated to heal in a very
      different manner, more resembling human normotrophic scarring. Given these
      observations, we studied microvessel density, an important aspect of wound
      healing, in human hypertrophic scars and the scars of the female Duroc and
      Yorkshire pigs. We studied microvessel density in uninjured skin; hypertrophic
      scars at 6 months or less, 7 to 12, and longer than 12 months; female Duroc
      tissues at 3 weeks and 3 and 5 months; and similar Yorkshire tissue, including
      uninjured skin and shallow and deep wounds. Antifactor VIII-related antigen was
      used to mark the endothelial cells. Computed assessment of microvessel density
      was used to quantify the microvasculature. In human hypertrophic scars, the
      microvessels were increased dramatically, and microvessel density and area were
      significantly elevated. We found similar results in the Duroc tissues at 5 months
      after deep wounding. In contrast, we found far less microvasculature and, at 5
      months, the values had returned to normal in the Yorkshire tissues. This
      quantitative study of microvessel density further validates the female Duroc pig
      as an animal model of hypertrophic scarring and the female Yorkshire pig as a
      control.

PMID- 17438499
TI  - Burned breast reconstruction by expanded artificial dermal substitute.
AB  - Full-thickness anterior chest wall burns result in contractures that may restrict
      the development of breast in young female patients. The management of postburn
      contractured anterior chest wall scars and unilateral breast hypoplasia with the
      expansion of bilayered artificial skin is herein presented for the first time in
      literature to the best of our knowledge. A 21-year-old female with chest wall
      contractures after thermal injury she had suffered at the age of 27 months was
      managed in three stages. The first stage included release and excision of
      contractures and scars, submuscular insertion of anatomical tissue expander, and
      coverage of the anterior chest wall with Integra artificial skin (Skin, Johnson &
      Johnson Medical, Division of Ethicon, Inc., Sommerville, NJ). One month later,
      the outer silicone layer of Integra was substituted by a split-thickness skin
      autograft and the expander was partly inflated with saline. During the third
      stage and after overexpansion of the expander had been completed, the expander
      was removed and a permanent silicone implant was subsequently inserted. No
      immediate or late complications were observed. At 17 months, the breast contour
      remains stable, no recontracture has occurred, and the patient evaluates the
      result as very satisfactory. Expansion of artificial skin Integra appears to be a
      reliable and safe alternative for reconstruction of the burned breast, lacking
      the morbidity associated with deep donor sites of full-thickness skin autografts
      or flaps.

PMID- 17438500
TI  - Reverse second dorsal metacarpal artery flap for reconstruction of fourth-degree
      burn wounds of the hand.
AB  - We sought to show how severe soft-tissue injuries of the proximal index finger
      caused by fourth-degree electrical burns to the hand may be surgically
      reconstructed. Soft-tissue coverage was provided with a reverse second dorsal
      metacarpal artery flap in two patients. Both digits were successfully salvaged by
      use of this reconstructive method. Both donor sites were closed primarily and
      healed without difficulty. The reverse second dorsal metacarpal artery flap
      provides well-vascularized tissue without excess bulk and allows near-normal hand
      function.

PMID- 17438501
TI  - Innate lymphocyte subsets and their immunoregulatory roles in burn injury and
      sepsis.
AB  - The vast majority of clinical and basic science research on the immune
      consequences of burn injury and sepsis conducted during the last three decades
      has focused mainly on the roles of macrophages, neutrophils and, to a lesser
      extent, conventional T lymphocytes. During recent years, however, it has become
      increasingly clear that minor subsets of innate immune cells, innate regulatory
      lymphocytes in particular, are central to processes involved in both protective
      immunity and immunopathology. Recent reports by our laboratory and others have
      just begun to shed light on the critical roles of innate lymphocyte subsets,
      including natural killer T cells, natural killer cells, gamma-delta T cells, and
      naturally occurring CD4+CD25+ regulatory T cells during the immune response to
      burn injury and sepsis. Given their emerging importance and documented upstream
      regulatory capacities over macrophage, dendritic cell, and T lymphocyte
      functions, innate regulatory lymphocytes represent attractive new targets for
      therapeutic intervention for the overall immune paralysis that occurs with injury
      and sepsis. Here, we provide an overview of the current state of knowledge of
      these particular cell subsets in the immune response to burn injury and sepsis.

PMID- 17438502
TI  - Noodles stay hotter longer.
AB  - During a 10-year period, a high incidence of burns from prepared noodle soup was
      noticed at the Baltimore Regional Burn Center. Because of the perceived severity
      of these burns, we took a more systematic look at the burns resulting from this
      type of soup to determine its effect on patient hospitalization and also examined
      the properties of the soup itself. All medical records of pediatric patients
      admitted to the Center between 1989 and 1999 with scald burns from various types
      of soup were retrospectively reviewed and divided into the Noodle Soup group, and
      the Other Soup group. The scald burns were compared as well as the physical
      properties of prepared noodle soup and tap water. Of 27 pediatric admissions for
      soup burns, 10 were from noodle soup and 17 from other types. Difference in
      average age and average total percentage of body surface area affected was not
      significant for the burns from either type of soup. However, the average length
      of stay for patients with noodle soup burns was significantly longer than for
      those with other types of soup burns (P < .010). Also, the cooling curve for
      noodle soup is much slower than for normal tap water. Noodle soup causes a
      significantly longer hospital stay than other types of soup. Because the boiling
      temperature of water and noodle soup is about the same, but the cooling curve of
      noodle soup is much slower, noodle soup may present a greater danger to children
      than other types of soup.

PMID- 17438503
TI  - Determination of inter-rater reliability in pediatric burn scar assessment using
      a modified version of the Vancouver Scar Scale.
AB  - The Vancouver Scar Scale is too subjective for our needs and is not culturally
      sensitive to our Aboriginal clients. The VSS was modified by developing a color
      scale to aid with vascularity rating. This study was designed to measure the
      inter-rater reliability of the modified Vancouver Scar Scale (MVSS). Three raters
      assessed 14 pediatric patients, resulting in a total of 32 scars. Data were
      analyzed using a Spearman Rank Order Correlation, intraclass correlation
      coefficient, and the kappa statistic. All subtests were shown to have significant
      (P < .05) correlations except for the pigmentation subtest. Because the
      pigmentation subtest has poor reliability, its inclusion in scar assessment
      should be questioned. Results indicate that only total scores of the MVSS should
      be used when determining burn scar outcomes because individual subtest scores
      appear to have little reliability. Further modifications to the MVSS followed by
      additional research with greater numbers of subjects are warranted.

PMID- 17438504
TI  - Comparison of fibrin sealant and staples for attaching split-thickness autologous
      sheet grafts in patients with deep partial- or full-thickness burn wounds: a
      phase 1/2 clinical study.
AB  - We undertook a multicenter, randomized, controlled, phase 1/2 clinical study to
      investigate the safety and efficacy of a fibrin sealant containing 4 IU/ml
      thrombin (FS 4IU) for the attachment of autologous sheet grafts in patients with
      deep partial-thickness or full-thickness burn wounds. Fibrin sealant (FS 4IU) was
      compared with staples for adherence of sheet grafts in 40 patients. Patients had
      to have burn wounds measuring 40% TBSA or less with two comparable test sites
      measuring between 1% and 4% TBSA each. Wound beds were prepared before treatment
      assignment, which was randomized. Percent area of hematoma/seroma at Day 1 (P =
      .0138) and questionable viability at Day 5 (P = .0182) were significantly less
      for FS 4IU-treated sites. Median percent area of graft survival on Day 14 was
      100% for both treatments (P = .3525). The percentage of completely closed sites
      generally was greater for FS 4IU-sites on Days 5 to 91; the maximum difference
      occurred at Day 28 (79.5% vs 59%; P = .0215). The safety profile of FS 4IU was
      excellent as indicated by the lack of any related serious adverse experiences.
      These findings indicate that FS 4IU is safe and effective for fixation of skin
      grafts, with outcomes similar to or better than staple fixation. The data suggest
      that FS 4IU is a promising candidate for further clinical studies focusing on
      skin graft adhesion and burn wound healing.

PMID- 17438505
TI  - Extended time to wound closure is associated with increased risk of heterotopic
      ossification of the elbow.
AB  - Heterotopic ossification (HO) is a well-recognized complication of burn injury
      that can result in significantly compromised limb function. The etiology and
      optimal treatment strategy for HO remain elusive. The purpose of this study was
      to examine the relationship between delay in elbow wound closure and the
      development of HO. We performed a case-control study to examine the relationship
      between delay in wound closure and development of HO. Cases (HO patients) were
      identified using our patient registry and matched with patients of similar age,
      burn size, and sex who did not develop HO. Time to wound closure was compared
      using bivariate statistics and the odds for developing HO based on time to wound
      closure was modeled using multivariate logistic regression. During the study
      period, a total of 45 patients developed elbow HO. When compared with controls
      matched for age, burn size, and sex, elbow wounds were open significantly longer
      in the cases than in the controls (48.7 days vs 24.2 days, P < .01). On
      multivariate logistic regression, the adjusted odds ratio was 1.08 (95% CI 1.04
      1.12, P < .01). Time to elbow wound closure significantly impacts the risk of
      development of heterotopic ossification. Therefore, to minimize risk of HO
      formation, increased attention is warranted to optimize time to wound closure
      over joints. In addition, consideration of other soft tissue coverage options
      such as local flaps, including fascia or muscle flaps, may be warranted in cases
      of very deep elbow buns with high risk of skin graft failure.

PMID- 17438506
TI  - The effect of positioning devices and pressure therapy on outcome after full
      thickness burns of the neck.
AB  - The postoperative management of full-thickness burns of the neck can be a
      challenge for burn therapists despite the availability of many treatment
      modalities to minimize scar hypertrophy and contracture. Interventions include
      pressure appliances, massage, exercise, and positioning devices. The objective of
      this study was to identify factors associated with the development of neck
      contractures and optimal treatment strategies for their prevention. We performed
      a retrospective chart review of all patients admitted to our pediatric burn
      center between 1989 and 2003 with acute full-thickness neck burns. Rehabilitation
      protocols used for each patient were examined. The necessity of a reconstructive
      procedure was analyzed, as well as time from initial grafting to that procedure.
      We identified 49 eligible subjects. Patients ranged in age from 0.6 to 14.2 years
      at the time of injury. The number of factors present which inhibited both
      positioning and application of pressure to the neck was found to be significantly
      related to the need for neck reconstruction (P < .01). Patients who had
      tracheostomies had a mean time to neck reconstruction of 20.3 months compared
      with 43.4 months in patients without tracheostomies (P < .05). Also, although not
      statistically significant, greater than 80% of patients who were discharged with
      reduced range of motion of the neck required reconstruction compared with fewer
      than 65% of patients with normal neck range. Delayed pressure and positioning of
      the neck after skin grafting result in an earlier and more frequent need for neck
      reconstruction.

PMID- 17438508
TI  - Time to school re-entry after burn injury is quite short.
AB  - Returning to school is an important indicator of functional aptitude and
      emotional adjustment in school-aged patients after burn injury. Only two reports
      in the burn literature provide objective data on time to school re-entry.
      However, these analyses did not address the impact of patient and burn injury
      characteristics on time to return to school. The purpose of this study was to
      determine the time for school re-entry and to identify the factors associated
      with re-entry time in a cohort of burned children treated at our burn center. We
      performed a retrospective review of all school age children treated at our burn
      center from 1997 to 2003 who were entered into a federally funded longitudinal
      research database for patients with severe burn injury. Time to school re-entry
      after discharge was calculated for each patient, and multivariate regression was
      used to identify the factors associated with longer time to return to school. A
      total of 64 patients were included in this study. The average time to school re
      entry was 10.5 days (range, 0-40) and the median time was 7.5 days. Gender
      (male), age, and length of hospital stay were significantly associated (P < .05)
      with longer time to return to school. The average time to school return is quite
      short. Further studies are needed to increase understanding of the factors
      influencing longer time to re-entry and also to examine children's experiences
      upon re-entry.

PMID- 17438509
TI  - Use of high-frequency percussive ventilation in inhalation injuries.
AB  - Inhalation injury causes significant morbidity and mortality, accounting for
      nearly 80% of non-fire-related deaths and affecting nearly 25% of all patients
      hospitalized with thermal injury. High-frequency percussive ventilation (HFPV)
      has been reported to decrease both the incidence of pulmonary barotrauma and
      pneumonia in inhalation injury. It has evolved into a ventilatory modality
      promoted to rapidly remove airway secretions and improve survival of patients
      with smoke inhalation injury. From 1997 to 2005, a total of 92 patients with
      inhalation injury were treated with HFPV. This group was compared with 130
      patients treated with conventional mechanical ventilation between 1997 and 2005.
      The diagnosis of inhalation injury was made on admission, based on the following
      clinical criteria: injury in a closed space, carbonaceous sputum, and/or positive
      bronchoscopy (presence of carbonaceous deposits, erythema or ulceration). Both
      modes of ventilation were begun within 24 hours of injury. Both groups were
      similar with respect to demographics and injury severity. The mean number of
      ventilator days, days in the intensive care unit, length of stay, and incidence
      of pneumonia did not differ significantly between groups. Twenty-six of 92 (28%)
      patients treated with HFPV, and 56 of 130 with conventional mechanical
      ventilation (43%) died. There was a significant decrease in both overall
      morbidity and mortality in the subset of patients with < or = 40% TBSA treated
      with HFPV. Future randomized, controlled trials are needed to determine the
      precise role of HFPV in the treatment of inhalation injuries.

PMID- 17438510
TI  - A silver impregnated antimicrobial dressing reduces hospital length of stay for
      pediatric patients with burns.
AB  - We sought to study whether the application of a novel silver impregnated
      antimicrobial dressing (Aquacel Ag, ConvaTec, Princeton, NJ) affects the hospital
      length of stay in pediatric patients with partial-thickness burns. A
      retrospective review of Burn Registry Data from a large children's hospital burn
      unit was conducted to answer this question. Pediatric patients admitted with
      partial-thickness burns treated with Aquacel Ag from January 2005 through August
      2005 were included in the study (n = 39). The comparison group of patients
      treated with silver sulfadiazine (SSD; Par Pharmeceuticals, Woodcliff, NJ) cream
      was matched for age and %TBSA burned from the same time period the previous year
      (n = 40). Analysis was conducted for intent to treat. Mean length of stay for
      control patients treated with SSD was significantly longer (8.36 days) compared
      with Aquacel Ag-treated patients (4.48 days; p = .002, t-test for unequal
      variances). Length of stay for both groups was significantly associated with
      %TBSA burned (p < .001, r2 = .38). Post-hoc analysis controlling for %TBSA burned
      revealed an adjusted mean length of stay for the control group that was longer
      than that of the Aquacel Ag group (5.9 days vs. 3.8 days, respectively). These
      data confirm that application of a new burn dressing (Aquacel Ag) reduces
      hospital length of stay. Reduction in the complexity and number of dressing
      changes needed with use of Aquacel Ag, in combination with significantly reduced
      length of stay, should result in a significant cost savings in the care of this
      patient population.

PMID- 17438511
TI  - The role of complementary and alternative medicine during the menopausal
      transition.

PMID- 17438512
TI  - The role of local vaginal estrogen for treatment of vaginal atrophy in
      postmenopausal women: 2007 position statement of The North American Menopause
      Society.
AB  - OBJECTIVE: To create an evidence-based position statement published by The North
      American Menopause Society (NAMS) on the role of local vaginal estrogen therapy
      (ET) for the treatment of vaginal atrophy in postmenopausal women. DESIGN: NAMS
      followed the general principles established for evidence-based guidelines to
      create this document. A panel of clinicians and researchers acknowledged to be
      experts in the field of genitourinary disease was enlisted to review, synthesize,
      and interpret the current evidence on vaginal ET for vaginal atrophy, develop
      conclusions, and make recommendations. Their advice was used to assist the NAMS
      Board of Trustees in publishing this position statement. RESULTS: Randomized
      controlled trials, albeit limited, have shown that low-dose, local vaginal
      estrogen delivery is effective and well tolerated for treating vaginal atrophy.
      All of the low-dose vaginal estrogen products approved in the United States for
      treatment of vaginal atrophy are equally effective at the doses recommended in
      labeling. CONCLUSIONS: The choice of therapy should be guided by clinical
      experience and patient preference. Progestogen is generally not indicated when
      low-dose estrogen is administered locally for vaginal atrophy. Data are
      insufficient to recommend annual endometrial surveillance in asymptomatic women
      using vaginal ET. Vaginal ET should be continued for women as long as distressful
      symptoms remain. For women treated for non-hormone-dependent cancer, management
      of vaginal atrophy is similar to that for women without a cancer history. For
      women with a history of hormone-dependent cancer, management recommendations are
      dependent upon each woman's preference in consultation with her oncologist.

PMID- 17438513
TI  - Are blood glucose levels affected by menopause?

PMID- 17438514
TI  - Cross-cultural comparisons of health-related quality of life in Australian and
      Japanese midlife women: the Australian and Japanese Midlife Women's Health Study.
AB  - OBJECTIVE: The purpose of this study was to address (1) the existence of an
      association between menopausal status and the health-related quality of life
      (HRQOL) in Australian and Japanese women and (2) the relative contributions of
      menopausal status, modifiable lifestyle risk factors, health, and
      sociodemographic factors on HRQOL. DESIGN: The Australian and Japanese Midlife
      Women's Health Study (AJMWHS) was a multisite, population-based study conducted
      in 2001 to 2002. Measures were conducted on data collected from a survey
      questionnaire used for a sample of women from Australia and Japan. HRQOL was
      assessed with seven subscales from the Short Form-36. RESULTS: The differences
      seen in physical functioning, general health, and vitality are significant. The
      results support an effect of country of residence on physical functioning and
      general health. The impact of menopausal status on HRQOL was significantly
      associated with bodily pain and role-emotional. The country of residence did have
      a modifying effect on the relationship between menopausal status and physical
      functioning. After control for confounders, there was a significant difference
      between Australian and Japanese women for HRQOL. Menopausal status was not
      associated with HRQOL in the areas of general health and physical functioning.
      Modifiable lifestyle risk factors contributed more highly to HRQOL for the
      Australian women than for the Japanese women. If the women had a lowered body
      mass index, undertook physical activity, consumed dietary phytoestrogens, and
      used alcohol, their physical functioning seemed to be better. Differences were
      seen in the contributions to HRQOL in these areas, with lower body mass index in
      the Australian women and physical activity in the Japanese women being the
      highest predictors. Somatic and psychological symptoms seem to negatively affect
      both Japanese and Australian women's physical functioning, contributing more than
      sociodemographic factors, menopausal status, and behavioral determinants combined
      to general health and physical functioning. CONCLUSIONS: It is important that
      that consideration be given to incorporating the same tool within the cross
      cultural design of studies so that comparisons between cultures and patterns of
      healthy aging can be made. The research suggests that there seems to be
      variations across Australian and Japanese midlife women in some areas of HRQOL
      and some factors that contribute to these areas.

PMID- 17438515
TI  - Estrogen effects on arteries vary with stage of reproductive life and extent of
      subclinical atherosclerosis progression.
AB  - The past several years have been marked by confusion and controversy concerning
      whether estrogens are cardioprotective. The issue is of utmost public health
      importance because coronary heart disease (CHD) remains the leading cause of
      death among postmenopausal women. Fortunately, a unifying hypothesis has emerged
      that reproductive stage is a major determinant of the effect of estrogens on
      atherosclerosis progression, complications, and plaque vulnerability.
      PREMENOPAUSAL YEARS: Premenopausal atherosclerosis progression seems to be an
      important determinant of postmenopausal atherosclerosis and thus the risk for
      CHD. Clearly, plasma lipids/lipoproteins influence this progression; however,
      estradiol deficiency seems to be the major modulator. Both monkeys and women with
      premenopausal estrogen deficiency develop premature atherosclerosis, an effect
      that can be prevented in both species by estrogen-containing oral contraceptives.
      PERIMENOPAUSAL/EARLY POSTMENOPAUSAL YEARS: During this stage, there are robust
      estrogen benefits. Monkeys given estrogens immediately after surgical menopause
      have a 70% inhibition in coronary atherosclerosis progression. Estrogen treatment
      prevented progression of atherosclerosis of women in the Estrogen in the
      Prevention of Atherosclerosis Trial. A meta-analysis of women younger than 60
      years given hormone therapy had reduced total mortality (relative risk = 0.61,
      95% CI: 0.39-0.95). LATE POSTMENOPAUSAL YEARS: This stage is one in which there
      are no or possible deleterious estrogen effects. Monkeys lose CHD benefits of
      estrogens when treatment is delayed. The increase in CHD events associated with
      initiating hormone therapy 10 or more years after menopause seems to be related
      to up-regulation of the plaque inflammatory processes and plaque instability and
      may be down-regulated by statin pretreatment.

PMID- 17438516
TI  - Age at natural menopause in Yazd, Islamic Republic of Iran.
AB  - OBJECTIVE: With increasing life expectancy, menopause is an increasingly
      important aspect of women's health. Although research suggests that age at
      menopause varies in different ethnic groups, data on age at menopause among
      Iranian women are limited. We recorded the age at natural menopause among women
      in a population-based study in Yazd, Islamic Republic of Iran, in 2006. DESIGN:
      This cross-sectional study estimates age at natural menopause among a sample of
      346 menopausal women through cluster sampling and according to their age and the
      onset of menopause (12 months of consecutive menstrual cessation). RESULTS: We
      found that the mean (SD) age at menopause was 47.39 (5.089) years (95% CI: 46.85
      47.92) and the median age was 48 years. The Iranian women demonstrated a moderate
      to high frequency of reporting four symptoms in vasomotor, vaginal, sleep
      related, emotional, and somatic categories. Physical factors (height, weight,
      body mass index, handedness) and sociodemographic factors (educational level,
      income) were not significantly related to early mean age at menopause.
      CONCLUSIONS: This study provides an estimate of age at menopause for Iranian
      center women, which is similar to the overall estimates previously reported for
      Iranian populations. Different factors influence age at natural menopause;
      however, there has not been a study in which this factor has been confirmed as a
      significant factor.

PMID- 17438517
TI  - Optimization of culture conditions for porcine corneal endothelial cells.
AB  - PURPOSE: To optimize the growth condition of porcine corneal endothelial cells
      (PCEC), we evaluated the effect of coculturing with a feeder layer (irradiated
      3T3 fibroblasts) with the addition of various exogenous factors, such as
      epidermal growth factor (EGF), nerve growth factor (NGF), bovine pituitary
      extract (BPE), ascorbic acid, and chondroitin sulfate, on cell proliferation,
      size, and morphology. METHODS: PCEC cultures were seeded at an initial cell
      density of 400 cells/cm(2) in the presence or absence of 20,000 murine-irradiated
      3T3 fibroblast/cm(2) in the classic media Dulbecco's Modified Eagle's Medium
      (DMEM) supplemented with 20% fetal bovine serum (FBS). Mean cell size and
      bromodeoxyuridine incorporation was assessed at various passages. Growth
      promoting factors were studies by seeding PCEC at 8,000 cells/cm(2) in DMEM with
      20% FBS or Opti-MEM I supplemented with 4% FBS and one of the following
      additives: EGF (0.5, 5, 25 ng/ml), NGF (5, 20, 50 ng/ml), BPE (25, 50, 100, 200
      microg/ml), ascorbic acid (10, 20, 40 microg/ml) and chondroitin sulfate (0.03,
      0.08, 1.6%), alone or in combination. Cell number, size and morphology of PCEC
      were assessed on different cell populations. Each experiment was repeated at
      least twice in three sets. In some cases, cell cultures were maintained after
      confluence to observe post-confluence changes in cell morphology. RESULTS: Co
      cultures of PCEC grown in DMEM 20% FBS with a 3T3 feeder layer improved the
      preservation of small polygonal cell shape. EGF, NGF, and chondroitin sulfate did
      not induce proliferation above basal level nor did these additives help maintain
      a small size. However, chondroitin sulfate did help preserve a good morphology.
      BPE and ascorbic acid had dose-dependent effects on proliferation. The
      combination of BPE, chondroitin sulfate, and ascorbic acid significantly
      increased cell numbers above those achieved with serum alone. No noticeable
      changes were observed when PCEC were cocultured with a 3T3 feeder layer in the
      final selected medium. CONCLUSIONS: Improvements have been made for the culture
      of PCEC. The final selected medium consistently allowed the growth of a contact
      inhibited cell monolayer of small, polygonal-shaped cells.

PMID- 17438518
TI  - Linkage and association of myocilin (MYOC) polymorphisms with high myopia in a
      Chinese population.
AB  - PURPOSE: To test the association between myocilin gene (MYOC) polymorphisms and
      high myopia in Hong Kong Chinese by using family-based association study.
      METHODS: A total of 162 Chinese nuclear families, consisting of 557 members, were
      recruited from an optometry clinic. Each family had two parents and at least one
      offspring with high myopia (defined as -6.00D or less for both eyes). All
      offspring were healthy with no clinical evidence of syndromic disease and other
      ocular abnormality. Genotyping was performed for two MYOC microsatellites (NGA17
      and NGA19) and five tag single nucleotide polymorphisms (SNPs) spreading across
      the gene. The genotype data were analyzed with Family-Based Association Test
      (FBAT) software to check linkage and association between the genetic markers and
      myopia, and with GenAssoc to generate case and pseudocontrol subjects for
      investigating main effects of genetic markers and calculating the genotype
      relative risks (GRR). RESULTS: FBAT analysis showed linkage and association with
      high myopia for two microsatellites and two SNPs under one to three genetic
      models after correction for multiple comparisons by false discovery rate. NGA17
      at the promoter was significant under an additive model (p=0.0084), while NGA19
      at the 3' flanking region showed significant results under both additive
      (p=0.0172) and dominant (p=0.0053) models. SNP rs2421853 (C>T) exhibited both
      linkage and association under additive (p=0.0009) and dominant/recessive
      (p=0.0041) models. SNP rs235858 (T>C) was also significant under additive (p=4.0E
      6) and dominant/recessive (p=2.5E-5) models. Both SNPs were downstream of NGA19
      at the 3' flanking region. Positive results for these SNPs were novel findings. A
      stepwise conditional logistic regression analysis of the case-pseudocontrol
      dataset generated by GenAssoc from the families showed that both SNPs could
      separately account for the association of NGA17 or NGA19, and that both SNPs
      contributed separate main effects to high myopia. For rs2421853 and with C/C as
      the reference genotype, the GRR increased from 1.678 for G/A to 2.738 for A/A
      (p=9.0E-4, global Wald test). For rs235858 and with G/G as the reference, the GRR
      increased 2.083 for G/A to 3.931 for A/A (p=2.0E-2, global Wald test). GRR
      estimates thus suggested an additive model for both SNPs, which was consistent
      with the finding that, of the three models tested, the additive model gave the
      lowest p values in FBAT analysis. CONCLUSIONS: Linkage and association was shown
      between the MYOC polymorphisms and high myopia in our family-based association
      study. The SNP rs235858 at the 3' flanking region showed the highest degree of
      confidence for association.

PMID- 17438519
TI  - HTRA1 promoter polymorphism predisposes Japanese to age-related macular
      degeneration.
AB  - PURPOSE: To study the effect of candidate single nucleotide polymorphisms (SNPs)
      on chromosome 10q26, recently shown to be associated with wet age-related macular
      degeneration (AMD) in Chinese and Caucasian cohorts, in a Japanese cohort.
      METHODS: Using genomic DNA isolated from peripheral blood of wet AMD cases and
      age-matched controls, we genotyped two SNPs, rs10490924, and rs11200638, on
      chromosome 10q26, 6.6 kb and 512 bp upstream of the HTRA1 gene, respectively,
      using temperature gradient capillary electrophoresis (TGCE) and direct
      sequencing. Association tests were performed for individual SNPs and jointly with
      SNP complement factor H (CFH) Y402H. RESULTS: The two SNPs, rs10490924 and
      rs11200638, are in complete linkage disequilibrium (D'=1). Previous sequence
      comparisons among seventeen species revealed that the genomic region containing
      rs11200638 was highly conserved while the region surrounding rs10490924 was not.
      The allelic association test for rs11200638 yielded a p-value <10(-11). SNP
      rs11200638 conferred disease risk in an autosomal recessive fashion: Odds ratio
      was 10.1 (95% CI 4.36, 23.06), adjusted for SNP CFH 402, for those carrying two
      copies of the risk allele, whereas indistinguishable from unity if carrying only
      one risk allele. CONCLUSIONS: The HTRA1 promoter polymorphism, rs11200638, is a
      strong candidate with a functional consequence that predisposes Japanese to
      develop neovascular AMD.

PMID- 17438520
TI  - Haplotype-tagging interleukin-10 promoter polymorphism is associated with reduced
      risk of retinal artery occlusion.
AB  - PURPOSE: Pro- and anti-inflammatory cytokines, including interleukin 10 (IL-10),
      play an essential role in atherogenesis. Increased IL-10 production has been
      found among carriers of the IL10 [TCATA] haplotype, which is formed by five
      polymorphisms at position -3575, -2763, -1082, -819, and -592 in the promoter
      region of the IL10 gene. Due to linkage disequilibrium, the presence of the
      [TCATA] haplotype can be unequivocally determined by analysis of the IL10-592C>A
      polymorphism. The purpose of the present study was to investigate a hypothesized
      association between the haplotype-tagging IL10 -592C>A polymorphism and the
      presence of retinal artery occlusion (RAO). METHODS: The present case-control
      study was comprised of 194 patients with RAO and 257 normal control subjects.
      Genotypes of the IL10 -592C>A polymorphism were determined by fluorogenic
      exonuclease (TaqMan) assay. RESULTS: Carriers of the IL10 -592A-allele,
      indicating the presence of the IL10 [TCATA] haplotype, were found significantly
      more often in controls than among patients with RAO (48.6% versus 36.1%;
      p=0.008). In a logistic regression analysis after adjusting for age, sex,
      arterial hypertension, diabetes mellitus, hypercholesterolemia, and smoking
      habits, carriage of the IL10 -592A-allele was associated with an odds ratio of
      0.65 (95% CI: 0.44-0.97) for RAO. CONCLUSIONS: Our data suggest that the IL10
      [TCATA] haplotype, identified by the presence of the IL10 -592A-allele, may exert
      a protective effect against RAO.

PMID- 17438521
TI  - Electroretinographic features of the retinopathy, globe enlarged (rge) chick
      phenotype.
AB  - PURPOSE: The purpose of the study was to characterize the electroretinographic
      features of the autosomal recessive retinopathy, globe enlarged (rge) phenotype,
      in chickens (Gallus gallus). METHODS: Dark-adapted, light-adapted intensity
      series and light-adapted 30 Hz flicker responses were recorded from rge and age
      matched normal control chicks from one to 270 days of age. Retinal sections from
      rge and control retinas were examined in 7 and 270-day-old chicks. RESULTS:
      Electroretinogram (ERG) thresholds of rge birds were raised, the intensity
      response plots were shifted toward brighter intensities, and retinal sensitivity
      was reduced. The leading slope of the dark- and light-adapted a-waves was more
      shallow than normal, suggesting altered photoreceptor responses. The inner
      retinal components to the ERG were also abnormal; there was a marked lack of
      oscillatory potentials and an abnormally smooth and broad shape to the b-wave.
      Additionally, the b-wave was supernormal in response to brighter stimuli in the
      earlier stages of the disease. There was a progressive deterioration in ERG
      amplitudes with age that mirrored a slowly progressive thinning of the
      photoreceptor layer. CONCLUSIONS: The rge chicken has unusual ERG changes from an
      early age with altered waveforms and initially they develop a supernormal b-wave.
      This is followed by a progressive reduction of ERG amplitudes with age. The
      changes suggest that both photoreceptor and inner retinal responses are abnormal.
      Additional studies are needed to further elucidate the origin of the abnormal ERG
      components in the rge chick.

PMID- 17438522
TI  - alpha-Crystallin distribution in retinal pigment epithelium and effect of gene
      knockouts on sensitivity to oxidative stress.
AB  - PURPOSE: To investigate the susceptibility of retinal pigment epithelium (RPE)
      from alphaA (-/-) and alphaB (-/-) mice to oxidative stress, and the subcellular
      changes of alphaA and alphaB-crystallins under oxidative stress. METHODS: The
      effect of hydrogen peroxide (H(2)O(2)) on apoptosis in RPE from alphaA (-/-),
      alphaB (-/-), and wild type (wt) mice was assessed by TUNEL and
      AnnexinV/Propidium Iodide assays. H(2)O(2)-induced changes in caspase-3 activity
      and mitochondrial permeability transition (MPT) were determined. Human RPE in
      early passages (2-4) were starved in 1% FBS-containing Dulbecco's modified Eagle
      medium (DMEM) and treated with H(2)O(2) for 24 h. Gene expression was quantitated
      by real time PCR. Confocal microscopy was used to examine alpha-crystallin
      compartmentalization. Whole cell and mitochondrial alpha-crystallin protein
      amounts were examined by transmission electron microscopy (TEM) and Western blot
      analysis. RESULTS: RPE from alphaA (-/-), alphaB (-/-) mice exhibited increased
      susceptibility to apoptosis induced by H(2)O(2), increased caspase-3 activation,
      and increased MPT. Treatment of human RPE with H(2)O(2) resulted in a dose
      dependent decrease in alphaB-crystallin mRNA expression. Confocal microscopy and
      subcellular fractionation of RPE showed that H(2)O(2) treatment decreased
      cytosolic and mitochondrial pools of alphaB-crystallin but caused no change in
      alphaA-crystallin content. TEM confirmed changes in expression of alphaA and
      alphaB-crystallins with oxidative stress. CONCLUSIONS: Lack of alpha-crystallins
      renders RPE cells more susceptible to apoptosis from oxidative stress.
      Mitochondrial alpha-crystallins may play an important role in the protection from
      increased susceptibility of RPE in oxidative stress.

PMID- 17438523
TI  - Involvement of ER stress in retinal cell death.
AB  - PURPOSE: To clarify whether endoplasmic reticulum (ER) stress is involved in
      retinal cell death, using cultured retinal ganglion cells (RGC-5, a rat ganglion
      cell line transformed with E1A virus), and transgenic mice ER stress-activated
      indicator (ERAI) mice carrying a human XBP1 and venus a variant of green
      fluorescent protein (GFP) fusion gene. METHODS: RGC-5 damage was induced by
      tunicamycin, and cell viability was measured by double nuclear staining (Hoechst
      33342 and either YO-PRO-1 or propidium iodide). The expressions of glucose
      regulated protein 78(GRP78)/BiP, the phosphorylated form of eukaryotic initiation
      factor 2alpha (p-eIF2alpha), and C/EBP-homologous (CHOP) protein after
      tunicamycin (in vitro or in vivo) or N-methyl-D-aspartate (NMDA; in vivo)
      treatment were measured using immunoblot or immunostaining. ERAI mice carrying
      the F-XBP1-DBD-venus expression gene were used to monitor ER-stress in vivo.
      Twenty-four hours after intravitreal injection of tunicamycin or NMDA, or after
      raising intraocular pressure (IOP), the retinal fluorescence intensity was
      visualized in anesthetized animals using an ophthalmoscope and in retinal
      flatmount or cross-section specimens using laser confocal microscopy. RESULTS:
      Treatment with tunicamycin induced apoptotic cell death in RGC-5 and also induced
      production of ER stress-related proteins (BiP, the phosphorylated form of
      eIF2alpha, and CHOP protein). In vivo, tunicamycin induced retinal ganglion cell
      (RGC) loss and thinning of the inner plexiform layer, 7 days after intravitreal
      injection. In flatmounted retinas of ERAI mice, the fluorescence intensity
      arising from the XBP-1-venus fusion protein, indicating ER-stress activation, was
      increased at 24 h after tunicamycin, NMDA, or IOP elevation. In transverse cross
      sections from ERAI mice, the fluorescence intensity was first increased in cells
      of the ganglion cell and inner plexiform layers at 12 and 24 h, respectively,
      after NMDA injection, and it was localized to ganglion and amacrine cells at 12
      and 24 h, respectively, and to microglial cells at 72 h. BiP and CHOP were
      increased at 12 h after NMDA injection, and the increases persisted for the
      remainder of the 72 h observation period. CONCLUSIONS: These data indicate that
      ER-stress may play a pivotal role in RGC death, whether induced by NMDA or IOP
      elevation.

PMID- 17438524
TI  - Low prevalence of lecithin retinol acyltransferase mutations in patients with
      Leber congenital amaurosis and autosomal recessive retinitis pigmentosa.
AB  - PURPOSE: To determine the the prevalence of pathogenic mutations in the gene
      encoding lecithin retinol acyltransferase (LRAT) in patients from North America
      with either Leber congenital amaurosis (LCA) or autosomal recessive retinitis
      pigmentosa (ARRP). METHODS: Exon 1, exon 2, and the coding region of exon 3 of
      LRAT were PCR-amplified and directly sequenced from the leukocyte DNA of 82
      unrelated patients with LCA and 190 unrelated patients with ARRP. RESULTS: One
      isocoding change was found in this screen of LRAT (Glu114 GAG>GAA; c.342), and 5
      other sequence changes were found in intronic or untranslated regions of the
      gene. None of these changes were predicted to affect the encoded protein and were
      therefore deemed non-pathogenic. CONCLUSIONS: LRAT mutations are likely a rare
      cause of LCA among patients from North America.

PMID- 17438525
TI  - The loss of transcriptional inhibition by the photoreceptor-cell specific nuclear
      receptor (NR2E3) is not a necessary cause of enhanced S-cone syndrome.
AB  - PURPOSE: To investigate functional consequence on photoreceptor-cell specific
      nuclear receptor (NR2E3) transcriptional activity of enhanced S-cone syndrome
      (ESCS) mutations localized in ligand binding domain (LBD). METHODS: Point
      mutations were introduced into the LBD of full length and Gal4 chimeric NR2E3
      receptors and transcriptional activity was investigated by using transient co
      transfection assay on corresponding luciferase reporters. Expression and DNA
      binding properties of transfected mutant and wild-type receptors were tested by
      Western blotting and gel shift assay. RESULTS: Our analysis show that two ESCS
      mutations, missense mutations R385P and M407K, abolished NR2E3 repressive
      activity in the context of full-length and Gal4 chimeric receptors, while W234S
      and R311Q mutants retained their repressive activity in both assays. All mutant
      receptors maintained their stability and DNA binding ability. CONCLUSIONS: These
      results showed that NR2E3 mutations localized in LBD induce ESCS disease without
      affecting inhibitory activity as recorded in vitro. This demonstrates the absence
      of correlation between transcriptional inhibition and ESCS phenotype. This
      analysis suggests that NR2E3 might have transcriptional activation properties not
      yet identified.

PMID- 17438526
TI  - Frequent methylation-associated silencing of a candidate tumor-suppressor,
      CRABP1, in esophageal squamous-cell carcinoma.
AB  - Epigenetic alterations and the resulting inactivation of tumor suppressor genes
      often contribute to the development of various cancers. To identify novel
      candidates that may be silenced by aberrant methylation in esophageal squamous
      cell carcinoma (ESCC), we analysed ESCC cell lines by a recently developed method
      known as bacterial artificial chromosome array-based methylated CpG island
      amplification (BAMCA), and selected candidates through BAMCA-assisted strategy.
      In the course of this program, we identified frequent CpG methylation-dependent
      silencing of the gene encoding cellular retinoic acid binding protein 1 (CRABP1)
      in our panel of ESCC cell lines. Expression of CRABP1 mRNA was restored in gene
      silenced ESCC cells after treatment with 5-aza 2'-deoxycytidine. The DNA
      methylation status of the CRABP1 CpG island with clear promoter activity
      correlated inversely with expression of this gene. CpG methylation of CRABP1 was
      frequently observed in primary ESCC tissues as well. Restoration of CRABP1
      expression in ESCC cells lacking the protein reduced cell growth by inducing
      arrest at G(0)-G(1), whereas knockdown of the gene in cells expressing CRABP1
      promoted cell growth. Among 113 primary ESCC tumors, the absence of
      immunoreactive CRABP1 was significantly associated with de-differentiation of
      cancer cells and with distant lymph-node metastases in the patients. These
      results indicate that CRABP1 appears to have a tumor-suppressor function in
      esophageal epithelium, and its epigenetic silencing may play a pivotal role
      during esophageal carcinogenesis. Its expression status in biopsies or resected
      tumors might serve as an index for identifying ESCC patients for whom combined
      therapeutic modalities would be recommended.

PMID- 17438527
TI  - Polyomavirus small T antigen transactivates genes by its ability to provoke the
      synthesis and the stabilization of MYC.
AB  - DNA tumor viruses are capable of driving quiescent cells into the cell cycle. In
      case of polyomaviridae, two viral proteins, the large and the small (ST) T
      antigens are responsible for this outcome. ST interacts with the protein
      phosphatase PP2A and with chaperons of the dnaK type and leads to the
      transactivation of several genes, which play a role in S-phase induction. One of
      these is the transcription factor myelocytomatosis (MYC), which by itself is an
      important regulator of growth. Microarray analysis has revealed several ST
      induced genes, which are also targets of MYC; hence, ST may induce these genes
      via MYC. Experiments shown here are in line with this assumption. MYC-regulated
      genes are induced by ST at later times than MYC and a MYC responsive promoter is
      stimulated by ST. Regulation of MYC occurs through signal transduction pathways,
      which are co-ordinated by PP2A suggesting that they may be targets of ST. Here,
      we show that this is the case as important kinases involved in these pathways
      appear in the active phosphorylated form in the presence of ST. Inhibition of
      these kinases interferes with MYC induction and inhibition of MYC activity blocks
      ST-mediated transactivation.

PMID- 17438528
TI  - Centriole overduplication through the concurrent formation of multiple daughter
      centrioles at single maternal templates.
AB  - Abnormal centrosome numbers are detected in virtually all cancers. The molecular
      mechanisms that underlie centrosome amplification, however, are poorly
      characterized. Based on the model that each maternal centriole serves as a
      template for the formation of one and only one daughter centriole per cell
      division cycle, the prevailing view is that centriole overduplication arises from
      successive rounds of centriole reproduction. Here, we provide evidence that a
      single maternal centriole can concurrently generate multiple daughter centrioles.
      This mechanism was initially identified in cells treated with the peptide vinyl
      sulfone proteasome inhibitor Z-L(3)VS. We subsequently found that the formation
      of more than one daughter at maternal centrioles requires cyclin E/cyclin
      dependent kinase 2 as well as Polo-like kinase 4 and that overexpression of these
      proteins mimics this phenotype in the absence of a proteasome inhibitor.
      Moreover, we show that the human papillomavirus type 16 E7 oncoprotein stimulates
      aberrant daughter centriole numbers in part through the formation of more than
      one daughter centriole at single maternal templates. These results help to
      explain how oncogenic stimuli can rapidly induce abnormal centriole numbers
      within a single cell-division cycle and provide insights into the regulation of
      centriole duplication.

PMID- 17438529
TI  - Loss of Arf causes tumor progression of PDGFB-induced oligodendroglioma.
AB  - In a subset of gliomas, the platelet-derived growth factor (PDGF) signaling
      pathway is perturbed. This is usually an early event occurring in low-grade
      tumors. In high-grade gliomas, the subsequent loss of the INK4a-ARF locus is one
      of the most common mutations. Here, we dissected the separate roles of Ink4a and
      Arf in PDGFB-induced oligodendroglioma development in mice. We found that there
      were differential functions of the two tumor suppressor genes. In tumors induced
      from astrocytes, both Ink4a-loss and Arf-loss caused a significantly increased
      incidence compared to wild-type mice. In tumors induced from glial progenitor
      cells there was a slight increase in tumor incidence in Ink4a-/- mice and Ink4a
      Arf-/- mice compared to wild-type mice. In both progenitor cells and astrocytes,
      Arf-loss caused a pronounced increase in tumor malignancy compared to Ink4a-loss.
      Hence, Ink4a-loss contributed to tumor initiation from astrocytes and Arf-loss
      caused tumor progression from both glial progenitor cells and astrocytes. Results
      from in vitro studies on primary brain cell cultures suggested that the PDGFB
      induced activation of the mitogen-activated protein kinase pathway via
      extracellular signal-regulated kinase was involved in the initiation of low-grade
      oligodendrogliomas and that the additional loss of Arf may contribute to tumor
      progression through increased levels of cyclin D1 and a phosphoinositide 3-kinase
      dependent activation of p70 ribosomal S6 kinase causing a strong proliferative
      response of tumor cells.

PMID- 17438532
TI  - Innovation and improvement in the treatment of obesity and diabetes.

PMID- 17438530
TI  - Stat5 activation inhibits prolactin-induced AP-1 activity: distinct prolactin
      initiated signals in tumorigenesis dependent on cell context.
AB  - The essential role of prolactin (PRL) in normal mammary gland growth and
      differentiation has implicated this hormone in the development and progression of
      breast cancer. Although Stat5 is the best-characterized mediator of PRL signals,
      PRL also activates multiple other signals, whose roles in normal and pathologic
      processes are not well understood. We have shown that PRL stimulates activating
      protein-1 (AP-1) activity in breast cancer cells, and can cooperate with
      estradiol in this pathway. AP-1 modulates many processes critical for
      carcinogenesis, including cell proliferation, survival, transformation, invasion
      and angiogenesis, and is elevated in many neoplasms, including breast tumors.
      Here, we investigated the relationship between PRL signals to AP-1 and Stat5. We
      found that PRL activation of Stat5a and Stat5b, but not Stat1 or Stat3, reduced
      PRL signals to AP-1, without altering estradiol-induced AP-1 activity. The
      truncation mutant, Stat5/Delta53C, but not Stat5Y699F, was an effective
      inhibitor, consistent with a requirement for Stat5 dimerization and nuclear
      accumulation, but not its C-terminal transactivation activity. The association of
      Stat5 with AP-1 proteins suggests that this underlies the inhibition.
      Predictably, the ability of PRL to activate Stat5 and AP-1 was inversely related
      in mammary cell lines. Further, reduction of Stat5 protein with siRNA in T47D
      cells, which contain elevated Stat5, increased PRL-induced AP-1 signals,
      transcripts for the AP-1 target, matrix metalloproteinase-2 and associated
      invasive behavior. This study points to the importance of cell context in
      determining the spectrum of PRL-induced actions, which is critical for
      understanding the contributions of PRL to breast cancer.

PMID- 17438535
TI  - Is the Dx for welfare Rx?
AB  - Welfare recipients in the United States are three times as likely to suffer from
      depression and anxiety as average Americans. Although affordable pharmacotherapy
      options are readily available in more affluent parts of society, welfare programs
      are ineffective in facilitating diagnosis and therapy that could help the
      affected improve their lives and even ultimately become gainfully employed and
      off taxpayer-supported welfare programs. To the benefit of all, more "bang for
      the buck" is within reach with common pharmacotherapy, but the question remains:
      who will wake up and champion the obvious?

PMID- 17438536
TI  - Aggressive management of obesity in children and young adults: the known
      challenges and potential opportunities.
AB  - The world is confronted with an impending epidemic of premature cardiovascular
      disease (CVD) that is being fueled by an increase in the prevalence of central
      obesity.

PMID- 17438537
TI  - Grapefruit juice, a glass full of drug interactions?
AB  - Numerous reports have documented drug interactions with grapefruit juice (GFJ)
      that occur via inhibition of CYP3A enzymes. As reported by Glaeser et al. in the
      March 2007 issue of this journal, there is increasing recognition that GFJ may
      also affect the activity of influx (e.g., OATPs) and efflux (e.g., P
      glycoprotein) transporters. This commentary focuses on these interactions between
      GFJ and drug transporters.

PMID- 17438538
TI  - Glutathione-S-transferase (GST) M1 null genotype and combined GSTM1 and GSTT1
      null genotypes as a risk factor for alcoholic mild liver dysfunction.

PMID- 17438539
TI  - Pharmacotherapy for the treatment of patients with type 2 diabetes mellitus:
      rationale and specific agents.
AB  - Type 2 diabetes, the most common form of diabetes, is characterized by
      abnormalities in hepatic glucose production, insulin resistance, and a
      progressive decline in beta-cell function over time. To treat effectively the
      individual with type 2 diabetes, the provider must have a thorough understanding
      of the underlying pathophysiology to provide treatment that precisely addresses
      the metabolic abnormalities. Currently, the provider who cares for subjects with
      type 2 diabetes can choose an antidiabetic agent from no less than eight
      pharmacologic classes. These classes include agents that increase insulin
      secretion, improve insulin action, and delay absorption of carbohydrates. The
      newer treatments available, specifically incretin therapy, address a previously
      unmet need in diabetes by modulating glucose supply. The currently available
      agents can be combined and combination therapy markedly improves glycemic
      control. This allows the provider to design regimens to specifically address
      underlying abnormalities. A review of all currently available agents is provided.

PMID- 17438542
TI  - Catalyzing collaboration.

PMID- 17438540
TI  - New targets for obesity pharmacotherapy.
AB  - An understanding of the mechanisms that regulate energy homeostasis is essential
      for understanding novel obesity therapies. The status of energy reserves is
      communicated to the brain by adiposity and satiety signals. These signals modify
      either anabolic or catabolic pathways and, consequently, alter food intake in
      line with signaled energy requirements. New antiobesity therapies are in
      development that target anabolic or catabolic regulatory networks to reduce food
      intake and/or increase energy expenditure to promote weight loss.

PMID- 17438543
TI  - EuCheMS.

PMID- 17438544
TI  - Assembling iron-sulfur clusters in the cytosol.

PMID- 17438545
TI  - Measuring H2O2 produced in response to cell surface receptor activation.

PMID- 17438546
TI  - Chemical probes of neural stem cell self-renewal.

PMID- 17438547
TI  - High-throughput screening flows along.

PMID- 17438548
TI  - Methyllysine analogs: rewriting the code.

PMID- 17438552
TI  - Involvement of annexin A2 in anti-beta2GPI/beta2GPI-induced tissue factor
      expression on monocytes.

PMID- 17438551
TI  - Engineering Escherichia coli for production of functionalized terpenoids using
      plant P450s.
AB  - Terpenoids are a highly diverse class of natural products that have historically
      provided a rich source for discovery of pharmacologically active small molecules,
      such as paclitaxel (Taxol) and artemisinin. Unfortunately, these secondary
      metabolites are typically produced in low abundance in their host organism, and
      their isolation consequently suffers from low yields and high consumption of
      natural resources. Furthermore, chemical synthesis of terpenoids can also be
      difficult to scale for industrial production. For these reasons, an attractive
      alternative strategy is to engineer metabolic pathways for production of
      pharmaceuticals or their precursors in a microbial host such as Escherichia coli.
      A key step is developing methods to carry out cytochrome P450 (P450)-based
      oxidation chemistry in vivo. Toward this goal, we have assembled two heterologous
      pathways for the biosynthesis of plant-derived terpenoid natural products, and we
      present the first examples of in vivo production of functionalized terpenoids in
      E. coli at high titer using native plant P450s.

PMID- 17438553
TI  - Mitotic phosphorylation of PRC1 at Thr470 is required for PRC1 oligomerization
      and proper central spindle organization.
AB  - During cell division, chromosome segregation is orchestrated by the interaction
      of spindle microtubules with the centromere. A dramatic remodeling of interpolar
      microtubules into an organized central spindle between the separating chromatids
      is required for the initiation and execution of cytokinesis. Central spindle
      organization requires mitotic kinesins, the chromosomal passenger protein
      complex, and microtubule bundling protein PRC1. PRC1 is phosphorylated by Cdc2 at
      Thr470 and Thr481 during mitosis. However, the functional relevance of PRC1
      phosphorylation at Thr470 has remained elusive. Here we show that expression of
      the non-phosphorylatable mutant PRC1(T470A) but not the phospho-mimicking mutant
      PRC1(T470E) causes aberrant organization of the central spindle.
      Immunoprecipitation experiment indicates that both PRC1(T470A) and PRC1(T470E)
      mutant proteins associate with wild-type PRC1, suggesting that phosphorylation of
      Thr470 does not alter PRC1 self-association. In addition, in vitro co
      sedimentation experiment showed that PRC1 binds to microtubule independent of the
      phosphorylation state of Thr470. Gel-filtration experiment suggested that
      phosphorylation of Thr470 promotes oligomerization of PRC1. Given the fact that
      prevention of the Thr470 phosphorylation inhibits PRC1 oligomerization in vitro
      and causes an aberrant organization of central spindle in vivo, we propose that
      this phosphorylation-dependent PRC1 oligomerization ensures that central spindle
      assembly occurs at the appropriate time in the cell cycle.

PMID- 17438550
TI  - Foldamers as versatile frameworks for the design and evolution of function.
AB  - Foldamers are sequence-specific oligomers akin to peptides, proteins and
      oligonucleotides that fold into well-defined three-dimensional structures. They
      offer the chemical biologist a broad pallet of building blocks for the
      construction of molecules that test and extend our understanding of protein
      folding and function. Foldamers also provide templates for presenting complex
      arrays of functional groups in virtually unlimited geometrical patterns, thereby
      presenting attractive opportunities for the design of molecules that bind in a
      sequence- and structure-specific manner to oligosaccharides, nucleic acids,
      membranes and proteins. We summarize recent advances and highlight the future
      applications and challenges of this rapidly expanding field.

PMID- 17438554
TI  - Cilia containing 9 + 2 structures grown from immortalized cells.
AB  - Cilia depend on their highly differentiated structure, a 9 + 2 arrangement, to
      remove particles from the lung and to transport reproductive cells. Immortalized
      cells could potentially be of great use in cilia research. Immortalization of
      cells with cilia structure containing the 9 + 2 arrangement might be able to
      generate cell lines with such cilia structure. However, whether immortalized
      cells can retain such a highly differentiated structure remains unclear. Here we
      demonstrate that (1) using E1a gene transfection, tracheal cells are
      immortalized; (2) interestingly, in a gel culture the immortalized cells form
      spherical aggregations within which a lumen is developed; and (3) surprisingly,
      inside the aggregation, cilia containing a 9 + 2 arrangement grow from the cell's
      apical pole and protrude into the lumen. These results may influence future
      research in many areas such as understanding the mechanisms of cilia
      differentiation, cilia generation in other existing cell lines, cilia disorders,
      generation of other highly differentiated structures besides cilia using the gel
      culture, immortalization of other ciliated cells with the E1a gene, development
      of cilia motile function, and establishment of a research model to provide
      uniform ciliated cells.

PMID- 17438555
TI  - Clinical efficacy of group-based treatment for childhood obesity compared with
      routinely given individual counseling.
AB  - OBJECTIVE: The aim of the study was to compare the efficacy of group treatment
      stressing a health-promoting lifestyle with routine counseling in the treatment
      of childhood obesity. DESIGN AND SUBJECTS: Seventy obese children (weight for
      height 115-182%) aged 7-9 years were randomized either to routine counseling (two
      appointments for children) or to family-based group treatment (15 separate
      sessions for parents and children). These sessions included nutrition education,
      physical activity education and behavioral therapy. OUTCOME MEASURES: Children's
      weights and heights were measured at baseline, after the 6-month intervention and
      after the 6-month follow-up. The change of weight for height based on Finnish
      growth charts was used as the primary, and changes in body mass index (BMI) and
      BMI standard deviation scores (BMI-SDS) as secondary outcome measures. RESULTS:
      Children attending the group treatment lost more weight for height (6.8%) than
      children receiving routine counseling (1.8%) (P=0.001). The difference was
      significant when the data were analyzed in four groups by the cut-off limits of
      0, -5 and -10% for the change in weight for height. The respective decreases in
      BMI were 0.8 vs 0.0 (P=0.003) and in BMI-SDS 0.3 vs 0.2 (P=0.022). The results
      remained similar in adjusted analyses. Both group and routine programs were
      feasible with a high, 87-99%, participation rate in sessions and appointments and
      very low, 3% or less, attrition rate from the programs. Six months after the
      intervention, beneficial effects were partly lost, but for changes in weight for
      height and BMI, the differences between the two treatment programs still were
      significant, and for BMI-SDS, there was a trend. CONCLUSIONS: Family-based group
      treatment that stresses a health-promoting lifestyle and is given separately for
      parents and children, offers an effective mode of therapy to treat obese school
      aged children.

PMID- 17438557
TI  - Inflammation and iron deficiency in the hypoferremia of obesity.
AB  - CONTEXT: Obesity is associated with hypoferremia, but it is unclear if this
      condition is caused by insufficient iron stores or diminished iron availability
      related to inflammation-induced iron sequestration. OBJECTIVE: To examine the
      relationships between obesity, serum iron, measures of iron intake, iron stores
      and inflammation. We hypothesized that both inflammation-induced sequestration of
      iron and true iron deficiency were involved in the hypoferremia of obesity.
      DESIGN: Cross-sectional analysis of factors anticipated to affect serum iron.
      SETTING: Outpatient clinic visits. PATIENTS: Convenience sample of 234 obese and
      172 non-obese adults. MAIN OUTCOME MEASURES: Relationships between serum iron,
      adiposity, and serum transferrin receptor, C-reactive protein, ferritin, and iron
      intake analyzed by analysis of covariance and multiple linear regression.
      RESULTS: Serum iron was lower (75.8+/-35.2 vs 86.5+/-34.2 g/dl, P=0.002), whereas
      transferrin receptor (22.6+/-7.1 vs 21.0+/-7.2 nmol/l, P=0.026), C-reactive
      protein (0.75+/-0.67 vs 0.34+/-0.67 mg/dl, P<0.0001) and ferritin (81.1+/-88.8 vs
      57.6+/-88.7 microg/l, P=0.009) were higher in obese than non-obese subjects.
      Obese subjects had a higher prevalence of iron deficiency defined by serum iron
      (24.3%, confidence intervals (CI) 19.3-30.2 vs 15.7%, CI 11.0-21.9%, P=0.03) and
      transferrin receptor (26.9%, CI 21.6-33.0 vs 15.7%, CI 11.0-21.9%, P=0.0078) but
      not by ferritin (9.8%, CI 6.6-14.4 vs 9.3%, CI 5.7-14.7%, P=0.99). Transferrin
      receptor, ferritin and C-reactive protein contributed independently as predictors
      of serum iron. CONCLUSIONS: The hypoferremia of obesity appears to be explained
      both by true iron deficiency and by inflammatory-mediated functional iron
      deficiency.

PMID- 17438558
TI  - Prevalence of impaired glucose regulation in German school-leaving students.
AB  - The increase in prevalence of obesity in childhood and adolescence appears to be
      followed by a rise of type 2 diabetes (T2D) cases in youth. Studies from the
      United States indicated that more than 1 in 10 adolescents may have disturbed
      glucose metabolism and that ethnicity and socioeconomic status are major
      determinants of (pre) diabetes prevalence. Since data for European countries are
      rare, we conducted a cross-sectional survey in 721 school-leaving boys and girls
      (mean age 15.5 years) in Dusseldorf (Germany). In our population from a
      predominantly low socioeconomic background, a total of 2.5% had impaired fasting
      glucose, impaired glucose tolerance or T2D. Hence, our study does not confirm the
      alarming data from high-risk US. American populations, but, nevertheless provides
      evidence for the necessity of public health interventions aiming at primary
      prevention of obesity and T2D in children and adolescents.

PMID- 17438559
TI  - Does using ethnic specific criteria improve the usefulness of the term metabolic
      syndrome? Controversies and suggestions.
AB  - The metabolic syndrome (MetS) is an important tool that identifies populations at
      increased risk for cardiovascular disease (CVD) and type 2 diabetes, targeting
      them for preventive measures. The criteria for the identification of the MetS
      were initially constructed from data in Caucasian populations. Recent research
      suggests that the current criteria for the MetS may not accurately characterize
      disease risk in non-Caucasian populations, either over or underestimating the
      risk in certain ethnic groups. Altering the criteria for each population by
      making ethnic-specific cutoffs as has been done with waist circumference will
      help in more accurate characterization. Using different combinations of the MetS
      criteria for different ethnic groups based CVD risk and factor analysis needs
      consideration. With better characterizations of patient populations, the ultimate
      goal would be to make MetS more accurate for predicting CVD risk while retaining
      the ease of screening afforded by the MetS. The proposed alterations of
      definition and criteria of the MetS would ensure its continued viability and
      sustainability.

PMID- 17438560
TI  - Concerning ephedra alkaloids for weight loss.

PMID- 17438561
TI  - Tolerance and autoimmunity: entwined pathways lead to immunological tolerance.

PMID- 17438562
TI  - Quantitative insights into stochastic monoallelic expression of cytokine genes.
AB  - Gene expression from both parental alleles is beneficial by masking the effects
      of deleterious recessive mutations and by reducing the noise in gene expression
      in diploid organisms. However, a class of genes are expressed preferentially or
      strictly from a single allele. The selective advantage of avoiding biallelic
      expression is clear for allelic-excluded antigen receptor and odorant receptor
      genes, genes undergoing X-chromosome inactivation in females and parental genomic
      imprinted genes. In contrast, there is no clear biological rationale for the
      predominant and stochastic monoallelic expression of cytokine genes in the immune
      system, and the underlying mechanism is elusive and controversial. A
      clarification of the mechanism of predominant monoallelic expression would be
      instrumental in better understanding its eventual biological functional. This
      prompted the development of a quantitative framework that could describe the
      dynamics of the pattern of allele expression of the IL-10 gene, from which
      general quantitative insights could be gained. We report that the experimental
      observations on these patterns of allelic expression cannot be easily reconciled
      with a simple model of stochastic transcriptional activation, in which the two
      alleles are, at any time, equally competent for transcription. Instead, these
      observations call into action a general model of eukaryotic transcriptional
      regulation according to which the locus competence for transcription is dynamic,
      involving multiple, cooperative and stochastic modification steps. In this model,
      the probability that an allele becomes transcriptionally active is a function of
      the number of chromatin modifications that it accumulated. On the basis of the
      properties of this model, we argue that predominant monoallelic expression might
      have had no adaptive role, and may have evolved under indirect selection for low
      frequency of expressing cells.

PMID- 17438563
TI  - The implantable cardioverter-defibrillator: patient care and quality of life.

PMID- 17438564
TI  - Total aortic root replacement versus valve-sparing surgery: providing a basis for
      comparison.

PMID- 17438565
TI  - Is clinical inertia a common barrier to patient care in type 2 diabetes mellitus?

PMID- 17438566
TI  - What is the prevalence and prognostic significance of esophageal varices in
      patients with hepatocellular carcinoma?

PMID- 17438567
TI  - How much symptom overlap is there between microscopic colitis and IBS?

PMID- 17438568
TI  - Sensation of defecation in patients with spinal cord injury.
AB  - STUDY DESIGN: For this study, a descriptive, explorative design was used.
      OBJECTIVES: As a result of spinal cord injury (SCI) patients may have a partial
      or complete loss of the sensations of defecation. To compensate this impairment,
      nurses initiate bowel management programs. Therefore, they need information about
      sensations of defecation. Accordingly, the research questions explore which
      sensations of defecation are reported by patients with SCI and whether they can
      be used to improve bowel care. SETTING: The Gemeinschaftskrankenhaus Herdecke and
      the Berufsgenossenschaftlichen Kliniken Bergmannsheil in Bochum, Germany.
      METHODS: A convenience sample of 27 patients with SCI was interviewed using a
      semistructured questionnaire. For data analysis, the frequency of the reported
      sensations was counted. RESULTS: The results of the study show that the
      participants' defecation was indicated by abdominal sensations (n=20) or a
      prickling sensation (n=11) emerging mainly in the head. Additional signals
      comprised increased spasticity (n=10), cutis anserina (n=8) and sweating (n=6).
      Seventeen participants sensed actual defecation and 15 perceived its cessation.
      Six participants were able to initiate defecating according to their sensations.
      CONCLUSIONS: The assessment of sensations of defecation in patients with SCI may
      indicate whether a bowel-management program with a consistent schedule for
      defecation is needed or if physiological defecation can be trained.

PMID- 17438571
TI  - Screening for fracture risk is mandatory in renal transplant patients on even low
      dose maintenance steroids.

PMID- 17438572
TI  - Should kidney transplantation be delayed in adolescents?

PMID- 17438573
TI  - Prospects for the use of NK cells in immunotherapy of human cancer.
AB  - Current insights into the molecular specificities that regulate natural killer
      (NK)-cell function suggest that it might be possible to design NK-cell-based
      immunotherapeutic strategies against human cancer. Here, we describe evidence for
      NK-cell targeting of human tumours and address crucial questions that, in our
      opinion, require consideration for the development of successful NK-cell-based
      therapies. Appropriately used, we predict that NK cells will have a role, both
      directly and in combination with other treatment modalities, in future treatment
      of cancer.

PMID- 17438574
TI  - New developments in FcepsilonRI regulation, function and inhibition.
AB  - The high-affinity Fc receptor for IgE (FcepsilonRI), a multimeric immune
      receptor, is a crucial structure for IgE-mediated allergic reactions. In recent
      years, advances have been made in several important areas of the study of
      FcepsilonRI. The first area relates to FcepsilonRI-mediated biological responses
      that are antigen independent. The second area encompasses the biological
      relevance of the distinct signalling pathways that are activated by FcepsilonRI;
      and the third area relates to the accumulated evidence for the tight control of
      FcepsilonRI signalling through a broad array of inhibitory mechanisms, which are
      being developed into promising therapeutic approaches.

PMID- 17438575
TI  - Graft-versus-host disease.
AB  - Allogeneic haematopoietic stem-cell transplantation (SCT) is a curative therapy
      for haematological malignancies and inherited disorders of blood cells, such as
      sickle-cell anaemia. Mature alphabeta T cells that are contained in the
      allografts reconstitute T-cell immunity and can eradicate malignant cells in the
      recipient. Unfortunately, these T cells recognize the recipient as 'non-self' and
      employ a wide range of immune mechanisms to attack recipient tissues in a process
      known as graft-versus-host disease (GVHD). The full therapeutic potential of
      allogeneic haematopoietic SCT will not be realized until approaches to minimize
      GVHD, while maintaining the positive contributions of donor T cells, are
      developed. This Review focuses on research in mouse models pursued to achieve
      this goal.

PMID- 17438576
TI  - Sentinel headaches in patients with subarachnoid hemorrhage: implications for
      patient management.

PMID- 17438577
TI  - Metabolic FDG-PET imaging in breast cancer: implications for treatment
      stratification.

PMID- 17438578
TI  - Borderline breast core needle histology: predictive values for malignancy in
      lesions of uncertain malignant potential (B3).
AB  - Breast core needle biopsy (CNB) is an accurate test but may result in borderline
      histology (lesions of uncertain malignant potential or B3). This is an evaluation
      of the largest series (to date) of B3 histology, which focuses on estimating
      positive predictive values (PPV) for malignancy. We identified all B3 CNBs over a
      10-year period in a single institution (N=372) from a series of 4035 consecutive
      needle biopsies. We describe the imaging findings, and report excision histology
      outcomes (N=279) and category-specific PPV for B3 lesions using two approaches
      including estimates based on subjects who had either excision or follow-up
      (N=328). B3 represented 9.2% of all CNB results. Excision histology was benign in
      181 (64.9%) and malignant in 98 (35.1%) subjects (61 ductal carcinoma in situ, 37
      invasive carcinoma). Positive predictive value for malignancy (based on excision
      histology) was 35.1% (95% CI: 29.5-40.7) and PPV (based on excision or review)
      was 29.9% (95% CI: 24.9-34.8). Lesion-specific PPV (estimates in parentheses for
      excision or follow-up) was atypical ductal hyperplasia 44.7% (40.6%); lobular
      intraepithelial neoplasia 60.9% (58.3%); papillary lesion 22.7% (15.9%); radial
      scar 16.7% (12.3%); phyllodes tumour 12.5% (12.5%); and B3 not specified 20.0%.
      Approximately one-third of CNB results classified as B3 are malignant on
      excision, and the likelihood of malignancy varies substantially between specific
      lesion groups. Whereas cases may be selectively managed without surgery, the
      majority warrant excision biopsy based on our estimates. Research is needed to
      improve differentiation between malignant and benign diseases in B3 lesions using
      diagnostic or predictive methods.

PMID- 17438583
TI  - Early fatal Rhizopus infection on voriconazole prophylaxis following allogeneic
      stem cell transplantation.

PMID- 17438584
TI  - Low-dose cidofovir treatment of BK virus-associated hemorrhagic cystitis in
      recipients of hematopoietic stem cell transplant.
AB  - In recipients of hematopoietic stem cell transplants (HSCTs), BK virus (BKV) has
      been associated with late-onset hemorrhagic cystitis (HC). In our institution,
      HSCT recipients with BKV-associated HC are treated with 1 mg/kg of cidofovir
      weekly. We identified HSCT recipients with BKV-associated HC, treated with weekly
      cidofovir. Microbiological response was defined as at least a one log reduction
      in urinary BKV viral load; clinical response was defined as improvement in
      symptoms and stability or reduction in the grade of cystitis. Nineteen allogeneic
      HSCT patients received a mean of 4.5 weekly doses of cidofovir. HC occurred at a
      mean of 68.7 days after transplant. A clinical response was detected in 16/19
      (84%) patients, and 9/19 (47%) had a measurable microbiological response (8/10
      nonresponders had a BKV viral load above the upper limit of the assay before
      treatment). Fourteen out of nineteen (74%) patients had no significant increase
      in serum creatinine. Five patients with renal dysfunction resolved after
      completion of the therapy and removal of other nephrotoxic agents. We conclude
      that weekly low-dose cidofovir appears to be a safe treatment option for BKV
      associated HC. Although the efficacy of low-dose cidofovir is not proven, a
      prospective trial is warranted.

PMID- 17438585
TI  - Epidemiology of bacteremia and factors associated with multi-drug-resistant gram
      negative bacteremia in hematopoietic stem cell transplant recipients.
AB  - The incidence of Gram-negative bacteremia has increased in hematopoietic stem
      cell transplant (HSCT) recipients. We prospectively collected data from 13
      Brazilian HSCT centers to characterize the epidemiology of bacteremia occurring
      early post transplant, and to identify factors associated with infection due to
      multi-drug-resistant (MDR) Gram-negative isolates. MDR was defined as an isolate
      with resistance to at least two of the following: third- or fourth-generation
      cephalosporins, carbapenems or piperacillin-tazobactam. Among 411 HSCT, fever
      occurred in 333, and 91 developed bacteremia (118 isolates): 47% owing to Gram
      positive, 37% owing to Gram-negative, and 16% caused by Gram-positive and Gram
      negative bacteria. Pseudomonas aeruginosa (22%), Klebsiella pneumoniae (19%) and
      Escherichia coli (17%) accounted for the majority of Gram-negative isolates, and
      37% were MDR. These isolates were recovered from 20 patients, representing 5% of
      all 411 HSCT and 22% of the episodes with bacteremia. By multivariate analysis,
      treatment with third-generation cephalosporins (odds ratio (OR) 10.65, 95%
      confidence interval (CI) 3.75-30.27) and being at one of the hospitals (OR 9.47,
      95% CI 2.60-34.40) were associated with infection due to MDR Gram-negative
      isolates. These findings may have important clinical implications in the decision
      of giving prophylaxis and selecting the empiric antibiotic regimen.

PMID- 17438586
TI  - Flow cytometry with anti HLA-antibodies: a simple but highly sensitive method for
      monitoring chimerism and minimal residual disease after HLA-mismatched stem cell
      transplantation.
AB  - Transplantation of HLA-mismatched stem cells may allow determination of chimerism
      status of single cells by differential expression of HLA molecules. Monoclonal
      antibodies against HLA antigens can be used to determine the HLA type of sub
      populations by standard flow cytometry. Blood samples from 23 patients
      transplanted from HLA-mismatched family donors were monitored using HLA-specific
      antibodies. Suitable antibodies could be found for all donor recipient pairs by
      using differences in HLA Bw4 and Bw6 groups or other serological antigens.
      Pretransplant controls of donor and recipient were used to correct for variable
      fluorescence intensities of the antibodies and sub-populations. Owing to the high
      sensitivity, cell populations with a minimum frequency of 0.1% were detectable.
      Flow-cytometric analysis was confirmed by chimerism analysis of
      immunomagnetically isolated T cells by standard PCR technique. In addition to
      chimerism evaluation, HLA antibodies improved the detection of leukemic cells
      after transplantation with aberrant phenotype. In conclusion, flow cytometry
      using antibodies against HLA antigens is an interesting tool for determination of
      chimerism and minimal residual disease after HLA-mismatched transplantation.
      Information about the chimerism status is given on a single-cell level and allows
      fast and convenient analysis of sub-populations.

PMID- 17438587
TI  - World Marrow Donor Association guidelines for use of HLA nomenclature and its
      validation in the data exchange among hematopoietic stem cell donor registries
      and cord blood banks.
AB  - Since the advent of the European Marrow Donor Information System in the first
      half of the last decade, fully automated data exchange between registry computer
      systems has been playing an ever-increasing role in the international search for
      unrelated donors of blood progenitor cells. This exchange, however, was hampered
      by different local conventions used to present HLA data and complicated by the
      need to extend the official WHO nomenclature to accommodate the registries'
      information systems and to cross-validate HLA data obtained with different
      methods and/or at different loci. The guidelines presented here have been
      developed by the World Marrow Donor Association to standardize the nomenclature
      to be used and the validation checks to be applied in the international
      electronic exchange of HLA-typing data among unrelated volunteer hematopoietic
      stem cell donor registries and umbilical cord blood banks. Two reference web
      sites have been designated to maintain and update the approved HLA nomenclature
      and all the ancillary information needed by the conventions described here.

PMID- 17438588
TI  - Symptom burden in patients undergoing autologous stem-cell transplantation.
AB  - Patients who undergo autologous peripheral blood stem cell (PBSC) transplantation
      experience multiple symptoms that adversely affect quality of life. We assessed
      symptoms during the acute phase of autologous PBSC transplantation to determine
      the severity of individual symptoms and to determine overall symptom profiles in
      100 patients with multiple myeloma or non-Hodgkin's lymphoma. Study subjects
      completed the blood and marrow transplantation module of the M. D. Anderson
      Symptom Inventory before hospitalization, during conditioning, on day of
      transplantation, at nadir (the time of lowest white blood cell count) and on day
      30 post-transplantation. Additional symptom, quality-of-life and medical status
      measures were collected. Symptom means were mild at baseline, intensified during
      conditioning, peaked at nadir and decreased by day 30. At nadir, the most severe
      symptoms for the entire patient sample were lack of appetite, fatigue, weakness,
      feeling sick, disturbed sleep, nausea and diarrhea. Cancer diagnosis was a
      significant predictor of changes in symptoms over time. The patterns of fatigue,
      pain, sleep disturbance and lack of appetite were significantly different for
      patients with multiple myeloma as compared with patients with non-Hodgkin's
      lymphoma.

PMID- 17438589
TI  - Ocular circulation in diabetic patients with coronary artery disease.
AB  - PURPOSE: To evaluate the ocular circulation in diabetic patients with coronary
      artery disease (CAD). METHODS: Thirty diabetic patients with diabetic retinopathy
      of grade 20 or 35, as evaluated by the Early Treatment Diabetic Retinopathy
      Study, were studied. They were divided into those without CAD (15 cases) and
      those with CAD (over 75% stenosis of carotid artery; 15 cases). All underwent
      standard ophthalmic examinations and orbital color Doppler imaging. Fifteen
      healthy controls underwent the same examinations. RESULTS: The peak systolic
      velocity in the central retinal artery was significantly lower in the two
      diabetic groups. The end-diastolic velocity in the central retinal artery was
      significantly lower only in the diabetic patients with CAD. There were no
      significant intergroup differences in blood flow velocities in the ophthalmic
      artery, short posterior ciliary artery, and central retinal vein. The blood flow
      waves were flattened in the diastolic phase for all orbital arteries in
      significantly more eyes in the diabetic patients with CAD. Echocardiography,
      performed only in the diabetic patients with CAD, showed that 10 cases (67%) had
      reduced systolic functions and/or diastolic functions and/or asynergy of the left
      ventricle. CONCLUSIONS: A decrease in blood flow velocities in the diastolic
      phase was found in diabetic patients with CAD. The findings indicate that this is
      probably related to the decrease in cardiac output.

PMID- 17438590
TI  - Current awareness on yeast.

PMID- 17438591
TI  - Clinical paradigms revisited.

PMID- 17438592
TI  - Clinical paradigms revisited.

PMID- 17438593
TI  - Gene symbol: LMNA.

PMID- 17438594
TI  - Clinical paradigms revisited.

PMID- 17438595
TI  - Gene symbol: MUTYH.

PMID- 17438596
TI  - Gene symbol: ATP7B.

PMID- 17438597
TI  - Gene symbol: PRPF31.

PMID- 17438598
TI  - Gene symbol: ATP7B.

PMID- 17438599
TI  - Gene symbol: SRY.

PMID- 17438600
TI  - Gene symbol: ARSA.

PMID- 17438602
TI  - What will the UK's hospital services look like in the future?

PMID- 17438601
TI  - Cuban doctors working abroad defect to the USA.

PMID- 17438603
TI  - Gene symbol: BRCA1.

PMID- 17438604
TI  - Gene symbol: LDB3.

PMID- 17438605
TI  - Gene symbol: SCN1A.

PMID- 17438606
TI  - Gene symbol: KCNH2.

PMID- 17438607
TI  - Gene symbol: SCN5A.

PMID- 17438608
TI  - Gene symbol: KCNH2.

PMID- 17438610
TI  - Gene symbol: SCN5A.

PMID- 17438609
TI  - Gene symbol: KCNQ1.

PMID- 17438611
TI  - Gene symbol: ARSA.

PMID- 17438612
TI  - Gene symbol: MUTYH.

PMID- 17438614
TI  - Gene symbol: MUTYH.

PMID- 17438613
TI  - Gene symbol: MUTYH.

PMID- 17438615
TI  - Gene symbol: CRB1.

PMID- 17438618
TI  - Gene symbol: MYH7.

PMID- 17438619
TI  - Gene symbol: MYH7.

PMID- 17438620
TI  - Gene symbol: SCN1A.

PMID- 17438621
TI  - [Lung cancer in Strandby].

PMID- 17438622
TI  - Gene symbol: LDB3.

PMID- 17438623
TI  - Gene symbol: ATP7B.

PMID- 17438624
TI  - Gene symbol: FBN1.

PMID- 17438625
TI  - Gene symbol: NOTCH3.

PMID- 17438626
TI  - Gene symbol: LMNA.

PMID- 17438627
TI  - Gene symbol: MUTYH.

PMID- 17438628
TI  - Gene symbol: LMNA.

PMID- 17438629
TI  - Gene symbol: MUTYH.

PMID- 17438630
TI  - The paradox of plenty: implications for performance measurement and pay for
      performance.

PMID- 17438631
TI  - Making the right things easier: physicians and evidence-based medicine.

PMID- 17438632
TI  - Employer perspective: transparency in health care.

PMID- 17438633
TI  - Health plan perspective: transparency and building a sustainable marketplace.

PMID- 17438634
TI  - Consumer perspective: health care communications.

PMID- 17438635
TI  - NLRB decision may harm patient care.

PMID- 17438636
TI  - Retroperitoneal approach.

PMID- 17438637
TI  - Forty-five years of schizophrenia: personal reflections.
AB  - Views about schizophrenia can change dramatically, even within one lifetime. In
      order to illustrate such changes over last forty-five years, this article uses
      the example of 'Mandy', a composite woman patient with a diagnosis of
      schizophrenia. It shows that, although there have been many advances over this
      period, understanding of schizophrenia continues to be elusive, and treatments
      remain imperfect. Therefore, as perspectives shift and the ground moves beneath
      us, the psychiatric profession needs to anchor itself firmly in the stories our
      patients tell us.

PMID- 17438638
TI  - [On the commentary (Akt. Urologie 2006;37:394-395].

PMID- 17438639
TI  - Intratracheal stent: prosthesis or orthesis?

PMID- 17438640
TI  - [Pro and contra. Renal partial resection: laparoscopy versus percutaneous
      ablative kidney tumor therapy. Pro laparoscopy].

PMID- 17438641
TI  - [Pro percutaneous-ablative tumor therapy].

PMID- 17438642
TI  - [How to stop recurrent macrohematuria in iliac-ureteral fistula].

PMID- 17438643
TI  - [From competitor to partner].

PMID- 17438644
TI  - Cooperation is key, say neuromuscular-disease researchers.

PMID- 17438645
TI  - [Slovenia: through reforms to a welfare state].

PMID- 17438646
TI  - [How a repressed doctoral student became a researcher of "repressed science": the
      scientific and the personal in the creative destiny of M. G. Iaroshevski].

PMID- 17438647
TI  - [The tragic story of the refusal to offer D. I. Mendeleev a position in the
      Russian Academy of Sciences in the 1880's].

PMID- 17438648
TI  - [Russian scientific emigration to Paris in the 19th century: general views and
      lessons].

PMID- 17438649
TI  - Chronic liver disease in a patient with sickle cell anemia.
AB  - Various disorders of the hepatobiliary system can occur due to sickling in
      patients with sickle cell anemia. Pathology and frequency of these disorders are
      not clearly known. Liver biopsies of these patients show erythrocytosis,
      erythrophagocytosis, sinusoidal dilatation and hyperplasia in Kupffer cells. We
      present a 21-year-old male patient diagnosed with sickle cell anemia who
      developed chronic liver disease, together with a review of the literature.

PMID- 17438650
TI  - Urinary metabolites and health effects in workers exposed chronically to
      chloronitrobenzene.
AB  - For workers exposed to 4-chloronitrobenzene (4CNB), the major metabolites were
      determined. Urine were analysed before and after acid hydrolysis to qualify the
      free and conjugated metabolites of 4CNB. Three conjugated metabolites were
      identified in exposed workers: the mercapturic acid N-acetyl-S-(4-nitrophenyl)-L
      cysteine (NANPC) was the only metabolite detected in non-hydrolysed urine, and
      accounted for approximately 51% of the total metabolites detected. The two
      remaining metabolites 4-chloroaniline (4CA) and 2-chloro-5-nitrophenol (CNP) were
      identified as cleavage products in hydrolysed urine, and accounted for
      approximately 18 and 30% of the total metabolites detected, respectively. No
      metabolites were found in factory controls within the limits of quantitation
      (LOQ) of the assay. There is a moderate correlation between NANPC and both 4CA
      and CNP. The correlation between 4CA and CNP is minor. The correlation between
      the total metabolites and both 4CA and CNP are good. The best correlation was
      found between the total metabolites and NANPC. There is a moderate inverse
      correlation between age and the creatinine levels. The raw metabolite levels CNP
      and NANPC decrease with age. The urine metabolites increase and correlate
      significantly with the creatinine levels. 4CA, NANPC and the total metabolite
      levels correlate with the haemoglobin adduct levels. NANPC is the most
      appropriate biomarker in the urine for a recent absorbed dose of 4CNB, since
      NANPC reflects the levels of 4CA and CNP and is the most prevalent metabolite
      detected in all the exposed workers.

PMID- 17438651
TI  - Comparison of biomarkers in workers exposed to 2,4,6-trinitrotoluene.
AB  - 2,4,6-Trinitrotoluene (TNT) is an important occupational and environmental
      pollutant. In TNT-exposed humans, notable toxic manifestations have included
      aplastic anaemia, toxic hepatitis, cataracts, hepatomegaly, and liver cancer.
      Therefore, methods were developed to biomonitor workers exposed to TNT. The
      workers were employed in a typical ammunition factory in China. The external dose
      (air levels and skin exposure), the internal dose (urinary metabolites), the
      biologically effective dose (haemoglobin adducts, urinary mutagenicity),
      biological effects (chromosomal aberrations and health effects), and individual
      susceptibility (genotypes of xenobiotic-metabolizing enzymes) were determined.
      Haemoglobin-adducts of TNT, 4-amino-2,6-dinitrotoluene (4ADNT) and 2-amino-4,6
      dinitrotoluene (2ADNT), and the urinary metabolites of TNT, 4ADNT and 2ADNT, were
      found in all workers and in some controls. The levels of the haemoglobin-adducts
      or the urinary metabolites correlated weakly with the skin or air levels of TNT.
      The urinary mutagenicity determined in a subset of workers correlated strongly
      with the levels of 4ADNT and 2ADNT in urine. The haemoglobin-adducts correlated
      moderately with the urinary metabolites and with the urinary mutagenicity. The
      genotypes of glutathione S-transferases (GSTM1, GSTT1, GSTP1) and N
      acetyltransferases (NAT1, NAT2) were determined. In general, the genotypes did
      not significantly influence the haemoglobin-adduct levels and the urine
      metabolite levels. However, TNT-exposed workers who carried the NAT1 rapid
      acetylator genotype showed an increase in urinary mutagenicity and chromosomal
      aberrations as compared with slow acetylators. The haemoglobin adduct 4ADNT was
      significantly associated with a risk of hepatomegaly, splenomegaly and cataract;
      urine metabolites and genotypes were not associated with health effects. These
      results indicate that a set of well-selected biomarkers may be more informative
      regarding exposure and effect than routinely performed chemical measurements of
      pollutants in the air or on the skin.

PMID- 17438653
TI  - Peroxisomal proteomic approach for protein profiling in blue mussels (Mytilus
      edulis) exposed to crude oil.
AB  - Peroxisomal proteomic protein profiles of exposure to marine pollution have been
      recently introduced in biomonitoring experiments. However, laboratory experiments
      to study the independent effect of common pollutants are needed to define a
      minimal protein expression signature (PES) of exposure to a specific pollutant.
      The aim of this study was to obtain PESs in blue mussels (Mytilus edulis) exposed
      to two different crude oil mixtures for future application in biomonitoring areas
      affected by oil spills. In the study, peroxisome-enriched fractions from
      digestive gland of M. edulis (L., 1758) were analysed by two-dimensional
      fluorescence difference electrophoresis (DIGE) and mass spectrometry (MS) after 3
      weeks of exposure to crude oil mixtures: crude oil or crude oil spiked with
      alkylated phenols (AP) and extra polycyclic aromatic hydrocarbons (PAH) in a
      laboratory flow-through system. A minimal PES composed by 13 protein spots and
      unique PESs of exposure to the two different mixtures were identified. A total of
      22 spots from the two-dimensional maps that had shown a significant increase or
      decrease in abundance in each of the exposed groups exposed were analysed. The
      hierarchical clustering analysis succeeded in discriminating the exposed groups
      from the control groups based on the unique PES. The PESs obtained were
      consistent with protein patterns obtained in previous field experiments. The
      results suggest that the protein profiles obtained by peroxisomal proteomics
      could be used to assess oil exposure in marine pollution assessments.

PMID- 17438652
TI  - Biomarkers of exposure to environmental tobacco smoke in infants.
AB  - Non-invasive biomonitoring of exposure to environmental tobacco smoke (ETS) by
      means of hair is attractive in children, although systematic evaluation is
      required in infants. The objective was to compare nicotine and cotinine
      concentrations in hair and plasma and parentally reported exposure to ETS in a
      birth cohort of 411 infants. Plasma was collected from 356 six-month-old infants
      and hair samples were collected from 368 one-year-old infants. Concentrations of
      nicotine and cotinine were measured by an optimized gas chromatography-mass
      spectrometry (GC/MS)-based method requiring 4 mg hair or 200 microl plasma.
      Information was obtained on the number of days with ETS exposure during the first
      year of life, the smoking habits of the parents, and the number of cigarettes
      smoked per day in the home. All three parentally reported indices of ETS exposure
      were significantly associated with the biomarkers, with clear dose response
      relationships. There was a significant association between days with ETS exposure
      and nicotine in hair at relatively low exposure levels (10-99 days per year),
      whereas the other biomarkers only showed significant increases at higher exposure
      levels. In conclusion, nicotine in hair appears to be the biomarker most strongly
      associated with parental reports on exposure to ETS in infants.

PMID- 17438654
TI  - Polymorphisms of 5,10-methylenetetralydrofolate reductase (MTHFR), fruit and
      vegetable intake, and the risk of stomach cancer.
AB  - Stomach cancer is a serious public health problem in China. 5,10
      Methylenetetralydrofolate reductase (MTHFR) may be involved in both DNA
      methylation and DNA synthesis. Folate deficiency is associated with cancer risk
      that may be modulated by a genetic variation in the MTHFR gene in folate
      metabolism. The main goal of this study was to evaluate the association between
      polymorphisms of the MTHFR gene and the risk of stomach cancer. This study also
      explored the modification effects of fruit and vegetable intake (one of the main
      constituents is folate) on the risk of this disease. A population-based case
      control study was conducted in Taixing, China, consisting of 206 newly diagnosed
      cases with primary stomach cancer and 415 healthy population controls.
      Polymorphisms of MTHFR C677T and A1298C were assayed by polymerase chain reaction
      restricted fragment length polymorphism (PCR-RFLP) techniques. The data were
      analysed using the logistic regression model. No obvious association between the
      MTHFR A1298C polymorphism and the risk of stomach cancer was observed in this
      study. The frequencies of 677 C/C, C/T, and T/T were 34.5, 50.9, and 14.6%,
      respectively, in controls. The frequency of the MTHFR 677 wild homozygotic
      genotype was 25.8% in cases, which was lower than that in controls (34.5%). The
      adjusted odds ratio (OR) for the MTHFR 677 any T genotype was 2.05 (95%
      confidence interval (CI), 1.26-3.34) when compared with the C/C genotype. In the
      low fruit and vegetable intake group an increasing trend was observed with the T
      allele exposure, p = 0.0056. The adjusted ORs were 1.68 (95% CI = 0.86-3.29) for
      the C/T genotype and 3.58 (95% CI = 1.46-8.75) for the T/T genotype,
      respectively. The MTHFR 677 any T genotype was associated with an increased risk
      of primary stomach cancer among the Chinese population. Folate deficiency might
      modify the MTHFR gene polymorphism and influence the risk of stomach cancer.

PMID- 17438655
TI  - Association between nucleotide excision repair gene polymorphisms and chromosomal
      damage in coke-oven workers.
AB  - The associations between several genetic polymorphisms of nucleotide excision
      repair genes (NER) and chromosome damage level were studied among 140 coke-oven
      workers exposed to a high level of polyaromatic hydrocarbons (PAHs) and 66 non
      exposed workers. Seven polymorphisms with functional potential in five NER genes
      (ERCC1, ERCC2, ERCC4, ERCC5 and ERCC6) were genotyped in the 206 study subjects.
      Multivariate analysis of covariance revealed that coke-oven workers with the
      ERCC1 19007 CC genotype had significantly higher cytokinesis-block micronucleus
      frequency (CBMN) (10.5 +/- 6.8 per thousand) than those with CT (8.1 +/- 6.6 per
      thousand, p = 0.01) or TT (6.6 +/- 3.7-/ per thousand p = 0.05) or CT+TT
      genotypes (7.5 +/- 6.3 per thousand, p = 0.004). The ERCC6 A3368G polymorphism
      was also associated with CBMN frequency among coke-oven workers. Subjects with
      the AA genotype have a significantly higher CBMN frequency (10.0 +/- 6.9 per
      thousand) than those with AG (6.7 +/- 4.2 per thousand, p = 0.05) or AG+GG
      genotypes (6.6 +/- 4.1 per thousand, p = 0.02). Stratification analysis revealed
      the significant associations between ERCC1 C19007T and ERCC6 A3368G, and the CBMN
      frequencies were only found among older workers. In addition, a significant
      association between ERCC2 G23591A polymorphism and CBMN frequencies was also
      found among older coke-oven workers. The results suggest that polymorphisms of
      ERCC1 C19007T, ERCC6 A3368G and ERCC2 G23591A are associated with the CBMN
      frequencies among coke-oven workers.

PMID- 17438657
TI  - [Gene polymorphism and gene expression in schizophrenia].
AB  - The author reviews relevant data on the neuropathology and molecular genetics of
      schizophrenia. Anatomical alterations are localized mainly in the hippocampus,
      dorsal thalamus and dorsolateral prefrontal cortex, and involve the morphology
      and molecular structure of the neurons and synapses. Several susceptibility genes
      [including COMT, dysbindin, neuregulin, DISCI, RGS4, GRM3, G72, PPP3CC, CHRNA7,
      PRODH2, Aktl, 5qGABA(A)] having physiological function in the brain have been
      identified and this supports the view of schizophrenia as a disorder of cerebral
      synaptic function. NMDA receptor-mediated glutamate transmission may be
      particularly involved, but disturbances of dopamine and GABA signalling seem to
      be linked as well. Based on recent data, an agreement is emerging between the
      roles of the genes on the molecular and synaptic levels and the understanding of
      the disorder at the neural systems level.

PMID- 17438656
TI  - P38 MAPK inhibitors suppress biomarkers of hypertension end-organ damage,
      osteopontin and plasminogen activator inhibitor-1.
AB  - The assessment of target organ damage is important in defining the optimal
      treatment of hypertension and blood pressure-related cardiovascular disease. The
      aims of the present study were (1) to investigate candidate biomarkers of target
      organ damage, osteopontin (OPN) and plasminogen activator inhibitor-1 (PAI-1), in
      models of malignant hypertension with well characterized end-organ pathology; and
      (2) to evaluate the effects of chronic treatment with a p38 MAPK inhibitor. Gene
      expression, plasma concentrations, and renal immunohistochemical localization of
      OPN and PAI-1 were measured in stroke-prone spontaneously hypertensive rats on a
      salt-fat diet (SFD SHR-SP) and in spontaneously hypertensive rats receiving
      N(omega)-nitro-L-arginine methyl ester (L-NAME SHR). Plasma concentrations of OPN
      and PAI-1 increased significantly in SFD SHR-SP and L-NAME SHR as compared with
      controls, (2.5-4.5-fold for OPN and 2.0-9.0-fold for PAI-1). The plasma levels of
      OPN and PAI-1 were significantly correlated with the urinary excretion of albumin
      (p < 0.0001). Elevations in urinary albumin, plasma OPN and PAI-1 were abolished
      by chronic treatment (4-8 weeks) with a specific p38 MAPK inhibitor, SB-239063AN.
      OPN immunoreactivity was localized predominantly in the apical portion of tubule
      epithelium, while PAI-1 immunoreactivity was robust in glomeruli, tubules and
      renal artery endothelium. Treatment with the p38 MAPK inhibitor significantly
      reduced OPN and PAI-1 protein expression in target organs. Kidney gene expression
      was increased for OPN (4.9- and 7.9-fold) and PAI-1 (2.8- and 11.5-fold) in SFD
      SHR-SP and L-NAME SHR, respectively. In-silico pathway analysis revealed that
      activation of p38 MAPK was linked to OPN and PAI-1 via SPI, c-fos and c-jun;
      suggesting that these pathways may play an important role in p38 MAPK-dependent
      hypertensive renal dysfunction. The results suggest that enhanced OPN and PAI-1
      expression reflects end-organ damage in hypertension and that suppression
      correlates with end-organ protection regardless of overt antihypertensive action.

PMID- 17438658
TI  - [Insight into illness and compliance in schizophrenic disorders].
AB  - Poor insight into illness is a characteristic and common phenomenon in
      schizophrenic disorders. Lack of insight may lead to poor clinical outcome, thus,
      research focused on this phenomenon could help develop effective treatment
      strategies. The relationship between compliance with treatment and insight is
      complex and it may be influenced mostly by specific components of insight. The
      aim of the present study was to review the current definitions of insight, the
      tools and questionnaires used for its measurement, as well as the relationship
      between insight and psychopathological symptoms. Three theoretical models
      developed for the explanation of impaired insight are described; the
      Psychological Defence Model, the Cognitive Deficit Model, and the
      Neuropsychological Deficit Model. The neurocognitive bases of impaired insight is
      given special attention in this article. Administration of second generation
      antipsychotics and psychosocial interventions (psychoeducation with problem
      solving procedures and motivating techniques) can improve insight, and enhance
      compliance with treatment, thus, optimizing long-term therapeutic outcome for
      schizophrenia patients.

PMID- 17438659
TI  - [Psychological aspects of home advantage].
AB  - It has been shown that home teams supported by their audience win over 50% of the
      games in sports competitions. Researchers have also been paying increased
      attention to this topic during the last 10-15 years. Their main goal, in addition
      to verifying the existence of this phenomenon, was to find explanatory factors
      which can be associated - at least partly - with the development of home
      advantage. Our study demonstrates the biological basis of this phenomenon through
      the connection between the hormone system and territoriality, moreover, it
      discusses in detail the four possible contributing factors: noise of the
      supporting audience; familiarity; travel and rules. Latest research has
      emphasized an evolutionary explanation of home advantage, which, beyond the
      context of sports competitions, tries to give an answer to the differences found
      between male and female coping strategies.

PMID- 17438660
TI  - [Assessment of therapeutic adherence using questionnaires in patients with
      schizophrenia].
AB  - INTRODUCTION: Continuous antipsychotic therapy is an essential part of treatment
      in schizophrenia and discontinuation increases the risk of psychotic relapses.
      Therapeutic adherence is a parameter influenced by multiple factors (affecting
      the doctor, the patient and his relatives), and its extent is determined by the
      interaction of these factors. The aim of this study was to identify factors which
      affect the schizophrenic patient's willingness to adhere to a treatment. METHODS:
      A survey was conducted using a self-rated questionnaire about compliance.
      Patients with schizophrenia, their relatives and their attending doctors filled
      out the questionnaires. Subjects were invited to participate from all over
      Hungary in order to make the sample as representative as possible. RESULTS: 909
      patients with schizophrenia, 73 doctors and 423 patient's relatives participated
      in this study. 41% of patients acknowledged that sometimes they decide
      voluntarily not to follow the instructions, while their doctors think that this
      rate is 57%. Almost half of the patients (42%) forget to take the medication, or
      they miss it because of other cognitive dysfunctions. In the opinion of doctors
      (49%) and relatives (55%) this problem affects more patients. CONCLUSION: It is
      imperative to improve adherence to treatment in patients with schizophrenia
      because missing a dose is a frequent problem even in those showing partial
      adherence and because such instances of non-adherence can have serious health
      consequences.

PMID- 17438661
TI  - [Investigation of the life situation of schizophrenic and paranoid patients at
      the Mental Health Care Institution in the City of Debrecen].
AB  - Even today we have to reckon with the serious personal and social consequences of
      schizophrenic diseases. In spite of medical treatment and nursing, psychiatric
      nursing homes have not been able to obtain real improvement in those serious
      consequences. AIM: To survey whether an improvement can be detected as compared
      to the situation 25 years ago: how the disease affects the fate and progress of
      our patients in certain areas (marital status, employment, disability,
      guardianship). METHOD: Doctors' notes and information obtained by nurses during
      visits about patients belonging to categories F20.029.9 of ICD, compared to a
      group of patients not suffering from schizophrenia (F40.0-F60.9). RESULTS: The
      data of 2,397 patients in total have been processed. Of these, 893 belonged to
      categories F20-29. Compared to the 1,504 patients not suffering from
      schizophrenia, only a 1/3 of them were employed and 12 times as many were on
      disability pension. Among those of 35-54 years of age, there were four times as
      many singles, fewer were married, and five times fewer had an employment, three
      times as many received disability pension. Less than 10% of those in category F20
      were employed, compared to 49% in the other group. The need for long-time
      treatment and nursing is shown by the fact that while the majority of those
      belonging to categories F40-69, no longer need nursing at about the age of 50,
      approximately 40% of those in F20 have to be nursed in their old age as well.
      CONCLUSION: There is a lot to be done to improve the quality of life of the
      patients and their rehabilitation. In these important tasks, both psychiatric
      nursing taking place in the residential area (community psychiatry) and social
      care will play an indispensable role.

PMID- 17438662
TI  - [Study of suicides and homicides between 1867 and 2004 with a historical
      epidemiological method].

PMID- 17438663
TI  - Umbilical cord length in urinary tract abnormalities associated with
      oligohydramnios: evidence regarding developmental pathogenesis.
AB  - We performed a retrospective review of the length of the umbilical cords of
      stillborn fetuses with renal agenesis, cystic kidneys, and bladder outlet
      obstruction and compared the cord length with normative data. Among the 41 cases,
      31 had umbilical cord lengths that were shorter than average. However, the
      remaining 10 cases had an average to increased cord length. Urinary output in
      those cases might have been sufficient in early pregnancy to allow adequate fetal
      activity and sufficient umbilical cord lengthening. We suggest that the length of
      the umbilical cord can have implications relative to the developmental
      pathogenesis of some congenital urinary tract abnormalities.

PMID- 17438664
TI  - Ultrastructural features of gaucher disease treated with enzyme replacement
      therapy presenting as mesenteric mass lesions.
AB  - The classical ultrastructural features of Gaucher disease include large numbers
      of intracytoplasmic, membrane-bound lysosomal inclusions containing
      characteristic tubular structures on an electron-lucent background, representing
      the periodic acid schiff (PAS)-positive Gaucher cells identifiable on light
      microscopy. Following enzyme replacement therapy (ERT), many of the
      manifestations of the condition are ameliorated, but persistent mesenteric
      lymphadenopathy has been reported, the ultrastructural features of which
      previously have not been described. Two children, aged 4 and 8 years old,
      respectively, both presented with persistent abdominal lymphadenopathy whilst
      receiving ERT for Gaucher disease. Needle core biopsies were carried out, that
      demonstrated collections of macrophages and only scattered storage-type cells on
      light microscopy. PAS staining was negative in one case and only focally positive
      in the other Electron microscopic examination, however, confirmed the cells
      represented macrophages, the cytoplasm of which contained scattered abnormal
      inclusions containing occasional twisted tubular structures of the type reported
      in classic Gaucher disease. ERT in Gaucher disease appears to reduce accumulation
      of the metabolic products at many sites. But for uncertain reasons, abdominal
      lymphadenopathy may occur containing macrophages that do not form granulomas or
      classic Gaucher cells on light microscopy. These probably represent incomplete
      clearance, incomplete/partial enzyme replacement, or possibly an unusual response
      to a relatively small amount of storage material.

PMID- 17438665
TI  - Pediatric HIV infection: diagnostic laboratory methods.
AB  - The diagnosis of HIV-1 infection in infants and children continues to present
      challenges. Currently available virologic assays are sensitive and specific and
      allow early detection of perinatally acquired HIV infection. Identification soon
      after birth allows for the rapid initiation of antiretroviral therapy and
      preservation of the infant's immune system. Serologic diagnostic methods,
      including HIV-ELISA, Western blot, and immunofluorescence Assay can be used to
      make the diagnosis of HIV infection in infants older than 18 months of age,
      children, and adolescents. Recently developed rapid tests allow for testing
      outside clinical sites, provide results in a short period of time, and allow for
      prompt initiation of effective prophylaxis in cases of exposure particularly
      maternal to child transmission. We discuss here the diagnostic management of HIV
      exposed infants and HIV-infected children.

PMID- 17438666
TI  - Pediatric HIV infection: immune and viral evaluation.
AB  - Advances in laboratory methods have driven improvements in the management and
      treatment of HIV infection. The methods to accurately and rapidly diagnose HIV
      infection in infants and children have been outlined in the previous article. In
      this review, the laboratory evaluation of infected children is described and
      methods to monitor progression of disease and response to therapy outlined.

PMID- 17438667
TI  - Otocephaly: report of five new cases and a literature review.
AB  - Otocephaly, characterized by mandibular hypoplasia or agnathia, ventromedial
      auricular malposition (melotia) and/or auricular fusion (synotia), and
      microstomia with oroglossal hypoplasia or aglossia, is an extremely rare
      anomalad, identified in less than 1 in 70,000 births. The malformation spectrum
      is essentially lethal, because of ventilatory problems, and represents a
      developmental field defect of blastogenesis primarily affecting thefirst
      branchial arch derivatives. Holoprosencephaly is the most commonly identified
      association, but skeletal, genitourinary, and cardiovascular anomalies, and situs
      inversus have been reported. Polyhydramnios may be the presenting feature, but
      prenatal diagnosis has been uncommon. We present five new cases of otocephaly,
      the largest published series to date, with comprehensive review of the literature
      and an update of research in the etiopathogenesis of this malformation complex.
      One of our cases had situs inversus, and two presented with unexplained
      polyhydramnios. Otocephaly, while quite rare, should be considered in the
      differential diagnosis of this gestational complication.

PMID- 17438668
TI  - Complex disease, gender and epigenetics.
AB  - Gender differences in susceptibility to complex disease such as asthma, diabetes,
      lupus, autism and major depression, among numerous other disorders, represent one
      of the hallmarks of non-Mendelian biology. It has been generally accepted that
      endocrinological differences are involved in the sexual dimorphism of complex
      disease; however, specific molecular mechanisms of such hormonal effects have not
      been elucidated yet. This paper will review evidence that sex hormone action may
      be mediated via gene-specific epigenetic modifications of DNA and histones. The
      epigenetic modifications can explain sex effects at DNA sequence polymorphisms
      and haplotypes identified in gender-stratified genetic linkage and association
      studies. Hormone-induced DNA methylation and histone modification changes at
      specific gene regulatory regions may increase or reduce the risk of a disease.
      The epigenetic interpretation of sexual dimorphism fits well into the epigenetic
      theory of complex disease, which argues for the primary pathogenic role of
      inherited and/or acquired epigenetic misregulation rather than DNA sequence
      variation. The new experimental strategies, especially the high throughput
      microarray-based epigenetic profiling, can be used for testing the epigenetic
      hypothesis of gender effects in complex diseases.

PMID- 17438669
TI  - Novel approaches to treatment of advanced colorectal cancer with anti-EGFR
      monoclonal antibodies.
AB  - The standard treatment of metastatic colorectal cancer (mCRC) is combination of 5
      fluorouracil/folinic acid with irinotecan or oxaliplatin-based chemotherapy.
      Epidermal growth factor receptor (EGFR) is overexpressed in 70%-80% of colorectal
      cancers (CRC). EGFR overexpression is known to be involved in carcinogenic
      processes, such as cell proliferation, apoptosis, angiogenesis and metastasis.
      Monoclonal antibodies targeting EGFR have shown antitumor activity and improved
      the efficacy of chemotherapy. Cetuximab is a chimeric immunoglobulin (Ig) G1 anti
      EGFR monoclonal antibody (MoAb). Several clinical studies have shown cetuximab,
      either as a single agent or in combination with irinotecan, having promising
      efficacy in patients with metastatic CRC. Cetuximab with 5-fluorouracil/LV
      (leucovorin) plus irinotecan or oxaliplatin-based chemotherapy has shown higher
      response rate and longer time to progression as first-line treatment of mCRC.
      Currently, there are no data showing that addition of cetuximab would prolong
      overall survival in randomized studies. Panitumumab, a fully human IgG2
      monoclonal antibody, has also shown antitumor activity against EGFR-expressing
      mCRC with less allergic reaction. Anti-EGFR MoAbs are well tolerated and have
      limited overlapping toxicities in combination with other cytotoxic drugs. The
      most common side effect of anti-EGFR MoAb is an acneform skin rash, which is a
      surrogate marker of efficacy of treatment with MoAbs. In this review, we will
      discuss the use of anti-EGFR MoAbs in the treatment of mCRC, with focus on
      cetuximab and panitumumab.

PMID- 17438670
TI  - Central and peripheral clocks in cardiovascular and metabolic function.
AB  - The molecular circadian clock entrains biological rhythms to a 24-hour schedule.
      Aspects of cardiovascular physiology and, indeed, the incidence of myocardial
      infarction and stroke are also subject to diurnal variation. The use of rodent
      models of disrupted clock function has begun to elucidate the role of the
      molecular clock in the pathophysiology of cardiovascular and metabolic disease.

PMID- 17438671
TI  - The role of transcription factors implicated in anterior pituitary development in
      the aetiology of congenital hypopituitarism.
AB  - The anterior pituitary gland is a central regulator of growth, reproduction and
      homeostasis, and is the end-product of a carefully orchestrated pattern of
      expression of signalling molecules and transcription factors leading to the
      development of this complex organ secreting six hormones from five different cell
      types. Naturally occurring and transgenic murine models have demonstrated a role
      for many of these molecules in the aetiology of combined pituitary hormone
      deficiency (CPHD). These include the transcription factors HESX1, PROP1, POU1FI,
      LHX3, LHX4, TBX19 (TPIT), SOX3 and SOX2. The expression pattern of these
      transcription factors, their interaction with co-factors and their impact on
      target genes dictate the phenotype that results when the gene encoding the
      relevant transcription factor is mutated. The highly variable phenotype may
      consist of isolated hypopituitarism, or more complex disorders such as septo
      optic dysplasia (SOD) and holoprosencephaly. Since mutations in any one
      transcription factor are uncommon, and since the overall incidence of mutations
      in known transcription factors is low in patients with CPHD, it is clear that
      many genes remain to be identified, and characterization of these will further
      elucidate the pathogenesis of these complex conditions, and also shed light on
      normal pituitary development.

PMID- 17438672
TI  - Understanding the molecular basis of celiac disease: what genetic studies reveal.
AB  - Celiac disease (CD) is characterized by a chronic immune reaction in the small
      intestine to the gluten proteins that are present in a (Western) daily diet.
      Besides the well known involvement of the HLA class II histocompatibility antigen
      (HLA)-DQ2.5 and -DQ8 heterodimers (encoded by particular combinations of the HLA
      DQA1 and -DQB1 gene) in CD and the minor contribution of the CTLA-4 gene,
      recently the myosin IXB (MYO9B) gene has also been found to be genetically
      associated. This review covers the general aspects of CD as well as current
      insight into important molecular aspects. We evaluate the role of susceptibility
      genes in CD by following gluten along its path from ingestion to uptake in the
      body, which leads us through the three aspects of CD's pathology. The first is
      the presence of gluten in the lumen of the intestine, where it is broken down by
      several enzymes. The second is the intestinal barrier through which gluten
      peptides pass. The third is the reaction of the immune system in response to
      gluten peptides, in which both the innate and the adaptive immune systems play a
      role. Our main conclusion, based on the current genetic and functional studies,
      is that we should look for causal genes in the barrier function as well as in the
      immune systems.

PMID- 17438674
TI  - Advances in treating insomnia.
AB  - Too often, insomnia is treated as a symptom without investigation of the cause.
      Insomnia may be a condition unto itself (primary insomnia), or it may be
      associated with a medical or psychiatric condition (comorbid insomnia), and it
      may be acute or chronic. Inadequate treatment often leads to significant
      frustration and lost productivity. We review the classification, pathophysiology,
      and treatment of insomnia and discuss how we can minimize its adverse
      consequences.

PMID- 17438673
TI  - Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR)
      family of genes protect against age-related macular degeneration:
      characterization, ethnic distribution and evolutionary implications.
AB  - BACKGROUND: Variants in the complement factor H gene (CFH) are associated with
      age-related macular degeneration (AMD). CFH and five CFH-related genes (CFHR1-5)
      lie within the regulators of complement activation (RCA) locus on chromosome
      1q32. Aims and Methods. In this study, the structural and evolutionary
      relationships between these genes and AMD was refined using a combined genetic,
      molecular and immunohistochemical approach. RESULTS: We identify and characterize
      a large, common deletion that encompasses both the CFHR1 and CFHR3 genes. CFHR1,
      an abundant serum protein, is absent in subjects homozygous for the deletion.
      Genotyping analyses of AMD cases and controls from two cohorts demonstrates that
      deletion homozygotes comprise 1.1% of cases and 5.7% of the controls (chi
      square=32.8; P= 1.6 E-09). CFHR1 and CFHR3 transcripts are abundant in liver, but
      undetectable in the ocular retinal pigmented epithelium/choroid complex. AMD
      associated CFH/CFHR1/CFHR3 haplotypes are widespread in human populations.
      CONCLUSION: The absence of CFHR1 and/or CFHR3 may account for the protective
      effects conferred by some CFH haplotypes. Moreover, the high frequencies of the
      402H allele and the delCFHR1/CFHR3 alleles in African populations suggest an
      ancient origin for these alleles. The considerable diversity accumulated at this
      locus may be due to selection, which is consistent with an important role for the
      CFHR genes in innate immunity.

PMID- 17438675
TI  - At what age should we discontinue colon cancer screening in the elderly?

PMID- 17438676
TI  - Recognizing and managing fibromuscular dysplasia.
AB  - Fibromuscular dysplasia typically occurs in young women and most commonly
      presents with hypertension, transient ischemic attack, stroke, or an asymptomatic
      cervical bruit. The disease is nonatherosclerotic and noninflammatory and most
      often affects the renal and carotid arteries, although almost any artery can be
      involved. On angiography, affected blood vessels characteristically resemble a
      string of beads in the most common type of fibromuscular dysplasia, medial
      fibroplasia. Patients with renal artery stenosis and hypertension or renal
      impairment should be treated with percutaneous transluminal angioplasty without a
      stent. Patients with fibromuscular dysplasia of the internal carotid artery
      should also be treated with angioplasty if they develop focal neurologic symptoms
      such as a transient ischemic attack or stroke.

PMID- 17438677
TI  - An 18-year-old with effort-related arm swelling.

PMID- 17438678
TI  - Managing varicella zoster infection in pregnancy.
AB  - Varicella zoster virus (VZV) infection can be serious for pregnant women and
      their babies, although it is rare. The implications of primary VZV infection vary
      with the gestational age at infection. For the mother, the risk of severe illness
      is greatest after mid-pregnancy, when she is relatively immunocompromised. For
      the fetus, the risk of congenital infection is greatest when maternal infection
      occurs in the first or second trimester. Maternal infection is preventable by
      preconception vaccination.

PMID- 17438679
TI  - HIV screening for all: the new standard of care.
AB  - The US Centers for Disease Control and Prevention has revised its recommendations
      for screening for human immunodeficiency virus (HIV) (MMWR Recomm Rep 2006;
      55(RR14):1-17) and now recommends HIV screening for all patients age 13 to 64
      years in all health care settings, including hospital emergency departments,
      urgent care clinics, inpatient services, sexually transmitted disease clinics,
      tuberculosis clinics, and primary care offices.

PMID- 17438680
TI  - Neuropathic pain.

PMID- 17438681
TI  - [The effect of nutrition support on the modulation of immune disturbance after
      burns].

PMID- 17438682
TI  - [The pattern of nuclear factor-kappaB activation in rats with endotoxin shock and
      its role in biopterin-mediated nitric oxide induction].
AB  - OBJECTIVE: To investigate the pattern of nuclear factor-kappaB (NF-kappaB)
      activation in rats with lipopolysaccharide( LPS) shock, and to explore the
      mechanism of NF-kappaB signal pathway in the biopterin-mediated nitric oxide(NO)
      induction, as well as its role in the development of multiple organ dysfunction
      syndrome ( MODS) secondary to endotoxin challenge. METHODS: Fourty-seven male
      Wistar rats were randomly divided into control group ( C, n = 8) , LPS group ( n
      = 24, with 8 rats at each time-points, and shock model was made by injection of
      same dosage of LPS) , and pyrrolidine dithiocarbamate (PDTC) treatment group (
      PDTC, n = 15, with 5 rats at each time-points, and the rats were injected with
      LPS and PDTC). The rats were sacrificed at 2,6,12 post-injection hour( PIH) , and
      the blood and tissue samples from liver, lungs and kidneys were harvested for the
      determination of NF-KB activity, GTP cyclohydrolase I (GTP-CH I ) , and inducible
      nitric oxide synthase (iNOS) mRNA expression in the liver, lungs and kidneys,
      plasma and tissue content of biopterin and NO, as well as hepatic and renal
      function, and pulmonary myeloperoxidase activity. RESULTS: NF-kappaB DNA binding
      activity in LPS group was rapidly enhanced in liver, lungs and kidneys after
      endotoxin challenge when compared with that in controls (e. g. in pulmonary
      tissue it was 26+/-6) , and it reached the peak at 2 PIH, which was 291 +/-44 in
      pulmonary tissue( P <0. 01). GTP-CH I mRNA expression and biopterin levels in the
      liver, lung and kidney of each group were obviously higher than those in control
      group( P <0.05 or 0.01) , and it maintained at high levels at 12 PIH.
      Additionally, different degrees of dysfunction of the above mentioned organs was
      observed. Treatment with PDTC, an inhibitor of NF-KB signal transduction pathway,
      could reduce NF-kappaB DNA binding activity, inhibit GTP-CH I and iNOS/NO mRNA
      expression, as well as BH4, and NO levels in various tissues. Meanwhile the
      multiple organ damage was significantly ameliorated by PDTC pretreatment.
      CONCLUSION: Endotoxin challenge can rapidly lead to activation of NF-kappaB in
      various tissues, and NF-KB pathway might markedly up-regulate the production of
      biopterin/NO following endotoxic shock. Inhibition of NF-kappaB pathway
      attenuates inflammatory response and ameliorates multiple organ dysfunction,
      which might be associated with its down-regulation of the excessive activation of
      iNOS mediated by biopterin.

PMID- 17438683
TI  - [Influence of signal transduction modulators on the secretory function of T
      lymphocytes in severely scalded mice and its mechanism].
AB  - OBJECTIVE: To investigate the influence of various signal transduction modulators
      on the splenic T lymphocytes secretion of IL-2 and IL-10 in severely scalded
      mice, and to explore its mechanism. METHODS: The mice were inflicted with 18%
      TBSA full-thickness scald by high-pressure heat vapour, and T lymphocytes were
      isolated from murine splenocytes through nylon wool column at 12 and 96 post
      scald hours (PSH). Then the cells were divided into following groups: i. e.
      control, scald, scald and modulator [1 ml of 50 micromol/L PKC inhibitor ( H-7) ,
      30 micromol/L tetradecanoylphorbol-13-acetate (TPA) , 10micromol/L nonreceptor
      tyrosine protein kinase inhibitor (herbimycin) , 25 microg/ml of mitogen
      activated protein kinase kinase inhibitor (PD098059) , 100 nmol/L Calcium
      ionophore ( A23187) were added to the cells, respectively] groups. The scald
      group was subdivided into S1 (with scald at 12 PSH) and S2 (with scald at 96 PSH)
      groups. The modulator group was subdivided into modulator, S1 and modulator( the
      modulators were added into cells at 12 PSH) , and S2 and modulator( the
      modulators were added to cells at 96 PSH) groups. The influence of modulators to
      T lymphocyte secretion of IL-2 and IL-10 were observed. RESULTS: After the
      addition of H-7, the IL-2 and IL-10 levels in each group were obviously lower
      than that in controls( P <0. 05 or 0.01) , and that in S1 and H7 group, S2 and H7
      group were obviously lower than that in scald group at corresponding time-points(
      P <0.01). The levels of IL-10, and especially IL-2 were elevated by TPA, but they
      were markedly lower than that in control group after PD098059 pretreatment. The
      secretion of IL-2 and IL-10 was significantly suppressed by herbimycin in S1 and
      herbimycin, and S2 and herbimycin groups, but those in Sl and A21387[ (2 417+/
      39) pg/ml, (2 793+/-25)pg/ml] , S2 and A21387 [ (921+/-50) pg/ml, (2 633+/
      35)pg/ml] groups were evidently higher than those in S1[ (1 542+/-40)pg/ml, (2
      390+/-15)pg/ml] , S2 [(328+/-19)pg/ml, (1 618+/-21)pg/ml,( P <0.05 or
      <0.01)]groups. CONCLUSION: PKC, calcium, MAPKK and TPK play critical roles in the
      dysfunction of splenic T lymphocyte secretion of IL-2 and IL-10 in severely
      scalded mice, among which TPK and PKC are mainly targeted to IL-2 secretion, and
      MAPKK is targeted to IL-10 secretion. TPA and A23187 can markedly rectify the
      disturbance of IL-2/IL-10 secretion ratio by increasing the IL-2 secretion after
      scald.

PMID- 17438684
TI  - [Influence of the escharectomy during stock stage on the peripheral lymphocyte
      apoptosis and the antigen presentation function of monocytes in peripheral blood
      of scalded rats].
AB  - OBJECTIVE: To investigate the influence of escharectomy at different time-points
      after burn injury on the lymphocyte apoptosis and the antigen presentation
      function of monocytes in peripheral blood of scalded rats. METHODS: One hundred
      and thirty-six Wistar rats were randomly divided into normal control ( C,n = 8 ),
      scald ( S, n = 64,without treatment after scald) , A ( n = 40, with escharectomy
      at 36 post-burn hour( PSH) ) , B ( n = 24, with escharectomy at 72 PSH ) groups.
      The rats in A , B, S groups were inflicted with 30% TBSA full-thickness scald.
      The rats in S group were sacrificed on 6,12,24,72,120,168,216, 288 PSH, while
      those in A and B groups were sacrificed at 72 -288 PSH, 168 -288PSH,
      respectively. The rats in C group were also sacrificed as control. The apoptotic
      rate of peripheral lymphocytes, the positive expression rate of MHC- II in
      mononuclear cells, the changes in concentration of IL-4 and gamma-IFN were
      determined in each group. The correlation of above indices were also analyzed.
      RESULTS: (1) The apoptotic rate of peripheral lymphocyte in S group were
      increased dramatically at 6PSH, peaking at 24 PSH( 18. 19+/-1.42% ) , then
      decreasing gradually, reaching the lowest level at 72 PSH(8. 25+/-0.56% ) , then
      it increased gradually again, approaching almost the peak value at 288 PSH( 17.81
      +/- 1.99% ). The values were all obviously higher than those in C group( P
      <0.05). The apoptotic rates of peripheral lymphocyte in A and B groups were
      evidently lower than that in S group ( P <0. 01). (2) The positive expression
      rate of MHC-II in monocyte was decreased sharply at 6 PSH, and it was 20% lower
      than that in C group (37. 2 +/- 2. 4% ) at 24 PSH. It then increased gradually,
      but it was significantly lower than that in A, B groups at 288 PSH (18. 8 +/-2.
      8, P <0.01). (3) The plasma level of y-IFN in S group increased gradually from 6
      PSH on, peaking at 24 PSH(440. 8 +/-25. 1 )ng/L,then decreasing gradually , and
      it reached the lowest level at 288 PSH (51.3 +/-37.0) ng/L. The IL-4 level in S
      group was increased gradually ,peaking at 288 PSH (78. 1+/-2. 8) ng/L. (4) There
      was negative correlation between the expression rate of MHC- II in S group and IL
      4/gamma-IFN ratio in escharectomy groups during 72 - 288 PSH ( r = - 0. 96, P <
      0. 05). CONCLUSION: Eacharectomy after scald can inhibit peripheral lymphocyte
      apoptosis, slow down the insertional tendency of IL-4/gamma-IFN , and ameliorate
      the antigen presentation function of monocytes. Moreover, escharectomy during
      shock stage can markedly promote the immune function of monocytes.

PMID- 17438685
TI  - [Influence of induced nitric oxide synthase expression on apoptosis of thymocyte
      in burn rats].
AB  - OBJECTIVE: To investigate the influence of induced nitric oxide synthase (iNOS)
      expression on apoptosis of thymocyte in burn rats, and to explore the
      relationship between NO and pathological lesion of the thymus gland in burn rats.
      METHODS: Fifty-six male Wistar rats were enrolled in the study and randomized
      into control( C, n = 8,without treatment) , burn ( B, n = 24) , and S
      methylisothiourea( SMT, n = 24) groups. Equal amount of isotonic saline solution
      and SMT(7. 5 mg/kg) were respectively intravenously infused into the rats in B
      and SMT groups after being inflicted with 30% TBSA full-thickness burns. The
      weight of thymus gland in each group were weighed, and thymocyte apoptosis and
      iNOS expression were determined with TUNEL method and immunohistochemistry,
      respectively at 6,24,72 postburn hours( PBH) , with 8 rats at each time-point.
      The number of apoptotic cells and the density of iNOS positive cells in thymus
      was measured by stereological method. RESULTS: The weight of thymus in B group at
      24 and 72 PBH [ (153+/- 14) , (91+/-22) mg] were obviously heavier than those in
      C group, but much lighter than those in SMT group ( P < 0.01). A few apoptotic
      cells and iNOS positive cells were observed in cortex and medulla of thymus in C
      group, while they were observed in B group at 6 PBH, and the number of cells
      began to increase at 24 PBH, distributing in medulla,parenchyma, the boundary of
      cortex, and medulla under capsule. The iNOS positive cells in B group at 24 PBH
      were distributed around the interlobular septum. A large number of cortical cells
      with brown staining were observed in B group at 72 PBH, and the number of iNOS
      positive cells also increased, with scattered distribution and clear cell
      boundary. Fewer positive cells with uneven distribution, no iNOS positive cells,
      and few apoptotic foci were observed in SMT group after burns. The density of
      apoptotic cells in B group at 24 and 72 PBH was (2. 428 +/-0. 728) x 10(
      5)/microm(3) and (5. 586 +/- 1.233) x 10(-5)/microm(3), respectively, which was
      obviously higher than that in C and SMT group. The density of iNOS positive cells
      in B group was increased in a time-dependent manner( P <0. 05). CONCLUSION: The
      apoptotic rate of thymocyte in severely burn rats increases early after burns.
      The up-regulation of iNOS expression in thymus can promote apoptosis of
      thymocytes, while SMT can partially ameliorate this phenomenon.

PMID- 17438686
TI  - [Experimental study on cryopreservation of immature dendritic cells derived from
      cord blood].
AB  - OBJECTIVE: To investigate the biological properties of immature dendritic cells(
      imDC) derived from cord blood before and after cryopreservation, so as to provide
      a method for preservation of imDC. METHODS: Immature dendritic cells were
      generated from human cord blood (CB) monocytes and cultured with rhGM-CSF and
      rhIL-4, and 10% DMSO was added into culture medium as cryopreservation reagent.
      After freezing in - 80 degrees C refrigerator, the cells were finally
      cryopreserved in - 196 degrees C liquid nitrogen, and then thawed with 40 'C
      water, and they were finally named frozen-thawed imDC. The morphology of imDC
      were observed with light microscope, and TBR were calculated. Cellular surface
      markers for DC maturation were determined with flow cytometry, and the ability of
      the cells to stimulate proliferation of non-sensitized T lymphocyte was
      determined with allogeneic mixed lymphocyte reaction. RESULTS: Monocyte (MNC)
      from cord blood could differentiate into DC after GM-CSF and rhIL-4 induction.
      Under light microscope, the cells showed irregular morphology, with branch-like
      prominence on the cell surface. Similar changes were also observed with scan
      electron microscope. The cryopreserved imDC were resistant to trypan blue
      staining, and TBR was (86. 8 +/- 1. 3) % . There was no obvious difference in the
      cell morphology between cryopreserved and fresh imDCs. The expression of cell
      surface markers and maturation markers in imDCs before cryopreservation were as
      follows: CDla(62 +/-8)% , CD14 (18 +/- 7)% , HLA-DR (67 +/- 5)% , CD80 (13+/-7)%,
      CD 86 (12+/- 5) % . Though the expression of CD80, CD86 and CD83 of cryopreserved
      imDC increased to (15 +/-5)% , (17 +/-5)% and (7.4 +/-3. 3)% , respectively( P
      <0.05), they still possessed the phenotype of imDC. There exhibited no obvious
      difference in cmp value between fresh imDC[ (463 +/- 104) min(-1) ] and
      cryopreserved imDC[ (512 +/-78 )min(-1) ] , ( P > 0. 05 ). The cpm in control
      group was (488 +/- 197 ) min'. The stimulation index in all groups was lower than
      2, and both fresh imDC and cryopreserved imDC could not stimulate the
      proliferation of non-sensitized T lymphocyte. CONCLUSION: The cryopreserved imDC
      exhibits immature characteristic in cell phenotypes, function and good cell
      activity, indicating that the method of cryopreservation of imDC is feasible.

PMID- 17438687
TI  - [Influence of the VEGF antibody targeted vascular therapy on the expression of
      collagen type I in hyperplastic].
AB  - OBJECTIVE: To investigate the influence of the vascular endothelial growth
      factor( VEGF) antibody targeted vascular therapy on the expression of human
      collagen type I in hyperplastic scar of nude mice. METHODS: The hyperplastic scar
      from one female burn patient with 1% TBSA deep-partial thickness burns were
      implanted into subcutaneous skin of scapular region of 48 nude mice. Three weeks
      later, the nude mice were divide into large dose (LA) , medium dose (MD) , small
      dose (SD) and control groups, with 12 mice in each group. The mice in LA,MD and
      SD groups were injected with 200 microl of 15,10, 5 microg/ml VEGF monoclonal
      antibody diluted in 0.01 mol/L PBS, respectively in the scar twice a week for 3
      weeks, while those in C group were injected with equal amount of 0. 01 mol/L PBS.
      The area and volume of the scar in each group were calculated and histological
      changes were observed, and the expression of collagen type I mRNA and its protein
      in each group were determined 3 days after treatment. RESULTS: The volume of scar
      in LA, MD, SD and C groups were (55.3 +/-4.1, 67.9 +/-5.7, 78.9 +/-5.5, 85.0
      +7.3) mm(3), respectively. Compared with that in C group, the volume of the scar
      were significantly decreased in AD and MD groups ( P <0.05). A few number of
      vessels and fibroblasts were observed in LD, MD groups, with decreased number of
      collagen fibers arranged in order. Compared with that in C group ,The expression
      of procollagen type I mRNA and its protein in C group was obviously higher than
      those in LD and MD groups ( P < 0. 05) , but it was similar to those in SD group.
      CONCLUSION: VEGF targeted vascular therapy is beneficial for the inhibition of
      the angiopoietins of hyperplastic scar, the expression of collagen , and the
      growth of scar.

PMID- 17438688
TI  - [Repair of the scar in the midface by skin expansion with parallel juxtaposed
      skin expanders].
AB  - OBJECTIVE: To explore a new method for the repair of the scar in the midface.
      METHODS: Parallel juxtaposed expansion of the skin and soft-tissue of jaw, face,
      neck and posterior aspect of auricle was performed to repair the scar in the
      midface of 15 patients. The operation consisted of two steps. In the first step,
      two expanders were placed subcutaneously under the subskin of jaw, face, neck and
      posterior aspect of the auricle, respectively, and they were expanded timely to
      create adequate superfluous skin and soft tissue. In the second step, the
      expanded skin flap was rotated and advanced to repair the the scar in the
      midface. RESULTS: Parallel juxtaposed expansion was performed to repair the scar
      in the midface of 15 patients. The incision was comparatively concealed, the
      colour and elasticity of the skin transplant, and the facial contours were
      satisfactory. CONCLUSION: Parallel juxtaposed expansion of the skin soft-tissue
      of jaw, face, neck and posterior auricular is beneficial for the repair of the
      scar in the midface.

PMID- 17438689
TI  - [Expression of insulin in the brain tissue of rats after scald].
AB  - OBJECTIVE: To observe the expression of insulin in the brain tissue of rat after
      scald. METHODS: Fifteen Wistar rats subjected to 30% TBSA scald were enrolled in
      the study. Zamboni fixating solution was infused into left ventricle and the
      brain tissue was harvested at 4, 12 and 24 post-scald hours (PSH) for the
      detection of insulin expression with fluorescent immunohistochemistry, with 5
      rats at each time-point. Another group of 10 rats were enrolled as controls.
      RESULTS: There exhibited no obvious insulin expression in the brain tissue of
      rats in the control group. Insulin immune responsive positive cells were detected
      in the olfactory bulb and cerebral cortex of rats at 4 PBH. These cells were big
      with oval and fusiform shape, big, round, transparent nuclei, and prominent
      processes. The positive insulin substance was mainly distributed in cytoplasm,
      and some in the processes of cells. No insulin immune-responsive cells were
      observed in rat brain tissue at 12 and 24 PSH. CONCLUSION: The brain have the
      potentiality of self-biosynthesis of insulin, but very little of synthesized
      insulin exists in normal states, but the amount increases after scald.

PMID- 17438690
TI  - [Repair of massive soft tissue defect in upper and lower extremities with free
      transmidline bi-lobed scapular skin flap].
AB  - OBJECTIVE: To evaluate the result of free transmidline bi-lobed scapular skin
      flap transplantation to repair massive soft tissue defects in upper and lower
      extremities. METHODS: Free transmidline bi-lobed scapular skin flap was designed
      according to the characteristics of scapular skin and its vasculature, and they
      were used to repair massive soft tissue defects in upper and lower extremities as
      a result of hot crush injury and avulsion injury in 9 patients. The survival of
      the flap, the blood supply, the color and elasticity of the flap, as well as scar
      contraction and impairment in function were observed after operation. RESULTS:
      The largest flap formed with the horizontal branch and descending branch
      circumflex scapular artery were 31 x 14 cm and 22 x 16 cm, respectively. The
      horizontal branch went across the spinal midline for 10 cm. All skin flaps
      survived with good elasticity and without necrosis. The grafted skin was
      excellent in the appearance and elasticity, with no scar contracture , and
      function of the injured extremities recovered well 2 to14 months after the
      operation. CONCLUSION: Free transmidline bi-lobed scapular skin flap is an ideal
      procedure for the repair of massive soft tissue defects in upper and lower
      extremities.

PMID- 17438691
TI  - [Observation of the effect of early fluid resuscitation on hepatic fatty
      degeneration in rats after severe scald].
AB  - OBJECTIVE: To investigate the efficacy of early fluid resuscitation on hepatic
      steatosis in rats after severe scald. METHODS: One hundred and forty-four Sprague
      Dawley rats were enrolled in the study. In thirty-six rats skin of 30% TBSA was
      treated with cold water to serve as sham injury group. All other rats were
      inflicted with 30% full-thickness scald, and they were subdivided into 3 groups,
      i. e. scald group(S, without resuscitation), delayed resuscitation group ( DR,
      with Ringer's solution at 6 post-scald hour(PSH) ) and early resuscitation group(
      ER, with Ringer's solution immediately after scald). The hepatic tissues of the
      rats were harvested at 0.5, 1.0,2.0,3.0,7.0 post-scald hour( PSH) and on 21.0 PSD
      for the observation of pathological changes with light-microscope and
      transmission electron microscope. The serum contents of TC, TG, HDL, ALP were
      determined at the same time-points. Body weight of each rat was measured before
      blood sampling, and total liver weight after blood sampling. Liver weight/body
      weight ratio was recorded. RESULTS: Compared with sham injury group, the fat
      denaturation degree of hepatic tissue in ER group was obviously less than that in
      S and DR group . The serum level of high density lipoprotein (TC) , triglyceride
      ( TG) , and alkaline phosphatase (ALP) after scald increased ranking as S > DR >
      ER, while the level of HDL decreased in that order. The liver weight/body weight
      ratio of the rats in DR group on 1.0 PSD was obviously elevated compared with
      that in ER group( P <0. 05) , and there exhibited significant difference of liver
      weight/body weight ratio between DR and ER groups on 7. 0 PSD ( P < 0. 01). The
      liver steatosis had obvious negative correlation with HDL content after scald( r
      = -0. 37, P <0.01) , but it had positive correlation with the ALP content( r = 0.
      45, P <0. 01), TG content( r = 0. 25, P <0. 01) and liver weight/body weight
      ratio( r = 0. 440, P <0. 01). The remaining parameters showed no correlation with
      the liver steatosis. CONCLUSION: Fluid resuscitation immediately after scald can
      ameliorate hepatic fatty degeneration, reduce its incidence, and beneficial to
      recovery of liver damage to a certain extent.

PMID- 17438692
TI  - [The antibacterial effect of cecropin B on pseudomonas aeruginosa infection of
      wounds in mice].
AB  - OBJECTIVE: To investigate the antibacterial effect of a particular antimicrobial
      peptide Cecropin B(CB) on Pseudomonas aeruginosa infection of wound in mice.
      METHODS: Thirty ICR mice were enrolled in the study, and the Pseudomonas
      aeruginosa infection model was reproduced by excision of the full layer of dorsal
      skin with an area of 1 cm x 1 cm. Then they were randomly divided into C (
      control, n = 10, with wet compress of isotonic saline at 3 postinjury hour( PIH)
      ) , M (with hydropathic compress of 100 g/L mafenide at 3 PIH), A (with wet
      compress of 1 000 mg/L Cecropin B at 3 PIH) groups. The changes in body
      temperature and hemogram in each group were determined before and 4 days after
      injury. Quantitative examination were used to detect the quantity of bacteria in
      muscular tissue of the wounds, and the survival of the mice were observed on 4
      post-injury day( PID). RESULTS: The wounds were moist with more exudation in C
      group,while that in other groups were dry without obvious exudation. The body
      temperature of the majority of the mice in each group were elevated, but the
      number of leucocytes in each group was lowered after operation. The quantity of
      bacteria in muscle in A group[ (42 +/- 50) CFU/g] was obviously lower than that
      in M group [(886+/-804) CFU/g, P <0.05] , and it was all obviously lower than
      that in C group[ (41 +/-28) x 10(5) CFU/g, P <0.01]. The number of surviving mice
      after 4 PID in C group was evidently smaller than that in A and M groups( P <0.
      05). CONCLUSION: The cecropin B possesses obvious anti-bacterial effect on the
      Pseudomonas Aeruginosa infected wounds of ICR mice, and it can reduce the
      mortality.

PMID- 17438693
TI  - [Effect of NF-kappaB activation on the early expression of tumor necrosis factor
      alpha and myocardial dysfunction in burned rats].
AB  - OBJECTIVE: To investigate the effect of NF-kappaB activation on the early
      expression of proinflammatory cytokines in myocardium and early myocardial
      dysfunction in burn rats. METHODS: One hundred and seventy Wistar rats were
      enrolled in the study and randomly divided into three groups, i. e. control( C, n
      = 20, with isotonic saline solution) , burn ( B, n = 90, with isotonic solution
      after burns) and pyrrolidine dithiocarbamate (PDTC, n =60, with isotonic saline
      and 250 mg/kg PDTC after burns) groups. The rats in B and PDTC groups were
      inflicted with 35% TBSA full-thickness burns on the back. The activity of
      myocardial NF-kappaB was determined by electrophoretic mobility shift assay at 1
      , 3, 6, 12,24 postburn hours (PBH), with expression of integral absorbance ( A )
      value . The expression of myocardial tumor necrosis factor alpha ( TNF-alpha)
      mRNA was assessed by reverse transcription polymerase chain reaction( RT-PCR) and
      in situ hybridization at 6, 12 PBH, with expression ofA value. The left
      ventricular systolic pressure( LVSP) , the left ventricular end diastolic
      pressure (LVEDP) ,the maximum rate of rise of left ventricular pressure ( +/-
      dp/dt max) were also observed at 3, 6, 12,24 PBH. RESULTS The activity of
      myocardial NF-KB in B group was markedly increased at 1 PBH [ (20. 3+/-3. 4) x
      104A ] ,which was obviously higher than that in C group (2. 2 +/- 0. 4) x 104A ,
      P <0.01]. It peaked at 3 PBH, and was still evidently higher than that in C group
      at 24 PBH ( P <0. 01). The expression of TNF-alpha mRNA was obviously higher than
      that in C group at 3 PBH ( P < 0. 01) , peaking at 6 PBH, and it was mainly
      expressed in myocardium. The expression of LVSP and +/- dp/dt max were lower, but
      LVEDP was higher than that in C group during 3 -24 PBH ( P <0.01).

PMID- 17438694
TI  - [Influence of mixed grafting of vascular endothelial cells and fibroblasts on the
      angiogenesis of artificial dermis].
AB  - OBJECTIVE: To evaluate the effects of mixed grafting of vascular endothelial
      cells and fibroblasts on the angiogenesis of artificial dermis. METHODS: Full
      thickness skin defects with the size of 2. 5 cm x 2. 5 cm were made on the back
      of 27 Wistar rats, and they were randomized into endothelium group ( cultured
      vascular endothelial cells were mixed into 0. 5 ml fibrin glue, and evenly
      sprayed onto wound bed in density of 1.0 x 10(5)/cm(2) before artificial dermis
      grafting) , mixed grafting group( cultured vascular endothelial cells and
      fibroblasts were mixed into 0. 5ml fibrin glue, and evenly sprayed onto wound bed
      in density of 1.0 x 10(5)/cm(2) before artificial dermis grafting) , and control
      group( with spraying of equal amount of fibrin glue on the wound bed). Each group
      consisted of 9 rats and 18 wounds. On 5 and 10 post-grafting day (PGF) , the
      grafts and surrounding tissue were harvested for the observation of neo-vascular
      growth with HE staining, VEGF antibody staining, Masson's trichrome staining and
      India ink staining. Evans blue perfusion method was also used to measure the
      angiogenesis of micro-vascular vessels on 5 PGD. RESULTS: The growth of new
      vessels was observed in each group on 5 PGD with HE staining, VEGF antibody
      staining, Masson's trichrome staining and India ink staining. Under high power
      field, the number of new vessels in endothelium and mixed grafting groups was
      (14. 2 3.6) and (12.1 +/- 2. 5) , which were obviously higher than that in
      control group (3.9 +/- 1.6, P < 0.05). On 10 PGD, angiogenesis and increased
      synthesis of collagen tissue were observed in both wound bed and artificial
      dermis. On 5 PGD, the amount of absorbed Even blue extracted from the grafted
      dermis in endothelium group (0. 167 +/-0. 058) and mixed grafting group (0. 155
      +/- 0. 046) was significantly higher than that in control group (0. 066+/-0. 024,
      P <0. 05). CONCLUSION: Mixed grafting of homogenous vascular endothelial cells
      and fibroblasts is beneficial for the promotion of neovascularization,
      acceleration of angiogenesis and maturation of artificial dermis during the wound
      healing process.

PMID- 17438695
TI  - [Clinical observation of xenoskin to cover microskin graft in the treatment of
      patients with deep burns].
AB  - OBJECTIVE: To explore the feasibility of application of xenoskin as microskin
      graft covering. METHODS: Ten patients with deep and extensive burns were enrolled
      in the study. A white pig weighing about 50kg was cleaned and shaved(without
      boiled water treatment) after being slaughtered. After conventional disinfection,
      two pieces of skin with little amount of fat were removed from the pig and
      processed to full-thickness or split-thickness skin. Before operation they were
      perforated and autogeneic microskin was scattered onto it. After escharectomy
      they were grafted on the wound, and the wound was dressed and bandaged with
      pressure. The rejection of the xenoskin, the survival of the microskin grafts,
      the wound healing time,and the functional recovery of the patients 1 year after
      operation were observed. RESULTS: The porcine skin was intact, and stuck well to
      the wound within 2 post-operation weeks ( POW). But it turned to form a dry scab,
      and gradually separated from the autogeneic microskin during 4 - 5 POW. The
      xenoskin completely fell off and the wound healed during 6 - 8 POW . The wound
      healing time of the 10 patients was 42 - 56 days [ (50 +/- 5) d]. Though there
      were thin scars 1 year after operation, the elasticity and function of the skin
      were normal. CONCLUSION: It is feasible to use porcine skin as a substitute of
      alloskin to cover autogenous microskin.

PMID- 17438696
TI  - [Influence of adenovirus transfection on the maturation characteristics of human
      immature dendritic cells].
AB  - OBJECTIVE: To observe the changes in the phenotype characteristics and immune
      function after transfection of cord blood derived immature dendritic cells( imDC)
      with Adeasy-EGFP adenovirus vector, and to explore the function of IL-10 in
      inhibition of imDC maturation. METHODS: Immature dendritic cells were generated
      from human cord blood(CB) monocyte cultured with rhGM-CSF and rhIL-4. The
      recombinant adenovirus vector AdEASY-EGFP was transduced into immature dendritic
      cells on the third day with or without adding IL-10. The expression of cell
      maturation marker CD83, CD86 and HLA-DR were determined with flow cytometry.
      Allogeneic mixed leukocyte reaction( MLR) was used to examine the imDC's ability
      to promote T cell proliferation. RESULTS: The expression of surface maturation
      markers of imDC after transfection with adenovirus were significantly up
      regulated ( CD86:46+/-10; CD83: 38 +/- 7; HLA-DR: 82 + 12) , and its ability to
      promote T cell proliferation was also obviously increased( SI > 2. 0). However,
      the expression of surface maturation markers of imDC after IL-10 treatment had
      lower mature phenotypes expression after transduction (CD86:8 +/- 5; CD83: 9 +/-
      3; HLA-DR:63 +/- 12), and T cell stimulating ability was decreased comparing with
      adenovirus transfection groups. CONCLUSION: Adenovirus can be transduced into
      imDC with high efficiency, but transfection itself can promote imDC's maturation.
      IL-10 treatment can inhibit the tendency to maturation stimulated by adenovirus
      transduction efficiently.

PMID- 17438697
TI  - [Clinical analysis of abdominal compartment syndrome in patients with serious
      burn injury].
AB  - OBJECTIVE: To summarize the clinical management of abdominal compartment syndrome
      (ACS) in burn patients with severe burn injury. METHODS: Twelve serious burn
      patients with abdominal compartment syndrome hospitalized in our center from
      January 2001 to April 2005 were enrolled in the study. Among them 3 patients were
      treated with conservative method, 4 with escharectomy of abdominal wall, 5 with
      laparotomy for decompression. The clinical results were analyzed statistically.
      Bladder pressure, central venous pressure, systolic blood pressure and arterial
      blood oxygen partial pressure (PaO2 ) were measured and compared before and after
      operation. RESULTS: Among these 12 patients, 5 died with the overall mortality of
      41.67%. But only 3 died among 9 patients undergone operation. Most of patients
      were oliguric,with abnormal bladder pressure, central venous pressure, and
      systolic blood pressure 24 hours before operation. But these parameters were
      significantly improved after operation ( P <0. 01). CONCLUSION: Early abdominal
      escharectomy and timely abdominal decompression are vital for the management of
      ACS in burn patients.

PMID- 17438699
TI  - Acta Oncologica--achievements during 2006 and a look at the future.

PMID- 17438698
TI  - [Amelioration of insulin resistance after scald by c-Jun N-terminal kinase
      inhibitor in rat].
AB  - OBJECTIVE: To investigate the role and mechanism of c-Jun N-terminal kinase (JNk)
      inhibitor (SP600125) in amelioration of insulin resistance after scald. METHODS:
      Twenty-four Sprague-Dawley rats were randomized into sham (the process of scald
      was mimicked by water at room temperature) , scald, scald and SP600125 groups.
      The rats were inflicted with 30% TBSA full-thickness scald in the latter two
      groups. Euglycemic-hyperinsulinemic glucose clamp experiment was carried out 4
      days after scald. SP600125 was administered to the rats in scald and SP600125 2
      hrs before Euglycemic-hyperinsulinemic glucose clamp was performed. Changes in
      the phospho-Serine307 and phospho-tyrosine of IRS-1 activity, as well as
      expression of phospho-JNK in muscles were determined. RESULTS: Euglycemic
      Hyperinsulinemic Glucose Clamps experiment showed that the infusion rate of 100
      g/L glucose in sham, scald, scald and SP600125 groups were (12. 33 +/-0. 42) ,
      (6. 61 +/-0. 27) , (11. 11 +/-0. 68) mgx kg(-1) x min(-1) , respectively ( P
      <0.01). The level of IRS-1 Serine307 phosphorylation and JNK activity in muscles
      were significantly increased, while insulin-induced tyrosine phosphorylation of
      IRS-1 decreased markedly after scald. Compared with scald group, the level of IRS
      1 Serine307 phosphorylation and JNK activity in scald and SP600125 group were
      decreased but tyrosine phosphorylation was elevated. CONCLUSION: SP600125 can
      partially ameliorate insulin resistance after scald by inhibition of JNK
      activation, and decrease the level of IRS-1 phospho-serine307.

PMID- 17438700
TI  - Clinical trials information monologues transform to dialogues.

PMID- 17438701
TI  - Optimized protein extraction from cryopreserved brain tissue samples.
AB  - Optimal standard conditions for protein extraction and solubilization from frozen
      tissue samples have been examined. Quantitative differences in specific protein
      amounts or post-translational modifications underlie many, if not all, disease
      states. Maximal and standardized extraction and solubilization of protein from
      diseased or healthy tissue is important to make the whole protein complement
      available for proteomic analysis, and to make the best use of a precious
      resource. Minimal degradation of the protein amino acid backbone, or of
      phosphorylated amino acid side chains, during sample preparation is essential to
      preserve the analytical utility of the extract. We have investigated parameters
      of brain tissue disintegration, and of extraction/solubilization temperature,
      time and volume and have reached 98% extraction of brain tissue, corresponding to
      about 100 microg protein per mg tissue wet weight, by an SDS-based method: Tissue
      disintegration in the frozen state, by ball mill grinding followed by extraction
      and solubilization in 2% SDS for 10 min, at 70 degrees C, in a volume
      corresponding to ten times the tissue wet weight, with shaking. The treatment
      with SDS sample buffer can inhibit protease and phosphatase activity. Moreover,
      endogenous enzymes can be inhibited by incubation at high pH. The resulting
      protein extracts can be used for both one-dimensional SDS gel-electrophoresis and
      for two-dimensional isoelectric focusing/SDS electrophoresis. The proposed
      standard protocol has the potential to find wide application where protein
      extraction, solubilization, identification and quantitation from cryopreserved
      clinical samples are desirable.

PMID- 17438702
TI  - Multiplex PCR for the detection of BCL-1/IGH and BCL-2/IGH gene rearrangements-
      clinical validation in a prospective study of blood and bone marrow in 258
      patients with or suspected of non-Hodgkin's lymphoma.
AB  - We have designed a multiplex PCR, which allows for fast and high throughput
      demonstration of the BCL-1/IGH and BCL-2/IGH fusion DNA observed primarily in
      mantle cell- and follicular non-Hodgkin's lymphoma (NHL). Blood (PB) and/or bone
      marrow (BM) from 258 patients suspected of NHL have prospectively been evaluated.
      Eleven patients (4%) were found t(11;14)+ and 37 patients (14%) t(14;18)+.
      Comparing these results to standard diagnostic methods of PB and/or BM identified
      PCR+ samples that were normal by morphology (BCL-1/IGH: 1/11; BCL-2/IGH: 17/37).
      Equally important, patients who were not clonal in PB and/or BM by flow cytometry
      were identified as PCR+ (BCL-1/IGH: 3/11; BCL-2/IGH: 23/37). We conclude that
      this multiplex approach allows for easy and sensitive molecular determination of
      molecular lesions in NHL, which have diagnostic and prognostic importance.

PMID- 17438703
TI  - Polymorphisms in XPD, XPC and the risk of death in patients with urinary bladder
      neoplasms.
AB  - We conducted a follow-up study on 311 patients with urinary bladder neoplasms to
      investigate the association of polymorphisms in DNA repair and cell growth
      regulatory genes with the clinical outcomes of this disease. We found that
      patients carrying the variant allele of XPD (K751Q) polymorphism were at lower
      risk of death (p = 0.04) than the noncarriers. Patients that were simultaneous
      carriers of variant alleles from XPD (K751Q) and XPC (K939Q) polymorphisms,
      showed lower risk of death than the other patients (p = 0.001). The variant
      allele carriers of MSH6 (G39E) polymorphism showed a higher risk for highly
      malignant disease (TaG3 +T1) than the non-carriers (p = 0.03). The variant allele
      carriers of XRCC1 (R399Q) polymorphism showed lower risk for recurrence (TaG2; p
      = 0.05) and death (T2+; p = 0.03) after instillation and radiotherapy than the
      non-carriers. After radiotherapy, an inverse association of the variant allele of
      OGG1 (S326C) polymorphism was observed with the risk of death (T2 +; p = 0.04). A
      significant low-risk for stage progression (p = 0.03) was observed in patients
      carrying the variant allele of H-ras (H27H) polymorphism. Our results are
      consistent with the notion that the XPD (K751Q) polymorphism either individually
      or in combination with the XPC (K939Q) polymorphism modulates the risk of death
      in patients with urinary bladder neoplasms.

PMID- 17438705
TI  - Participating in a cancer clinical trial? The balancing of options in the
      loneliness of autonomy: a grounded theory interview study.
AB  - Cancer patients asked to participate in a randomised trial including chemotherapy
      at two university centres and a satellite centre were interviewed about
      perceptions and experiences (14 trial participating and 15 trial declining
      patients). The central phenomenon was a constant, cautious balancing of personal
      options searching for maximised effect, personal safety, trust, confidence and
      being cared for. Almost all developed a treatment preference and this was
      decisive for choices. Trial participants strongly wished to get the experimental
      treatment perceived as superior. They felt their freedom of choice being limited
      by randomisation. In contrast, trial decliners almost all focused on graver
      adverse effects related to the experimental treatment. A trusting and confident
      doctor-patient relationship was valued strongly. Yet, most breast cancer patients
      treated at the two large centres experienced a general lack of personal trust,
      confidence and being taken care of. The major reason was patients meeting too
      many physicians perceived as incompetent and unprepared. In contrast, the ovarian
      cancer patients treated at the satellite centre were content and satisfied with
      the main reason being the low number of physicians who were perceived as
      prepared, empathetic and knowledgeable. All patients expressed a feeling of
      "loneliness of autonomy" lacking sufficient knowledge and other resources to make
      educated choices.

PMID- 17438704
TI  - A short communication course for physicians improves the quality of patient
      information in a clinical trial.
AB  - We investigated whether a short course in communication skills for physicians
      would improve the quality of informed consent in a randomized clinical adjuvant
      trial on breast cancer. In this prospective, case-controlled intervention study,
      physicians and research nurses who introduced the cancer treatment trial to
      patients at three of the participating hospitals first attended a one-day
      communication skills course. The quality of informed consent was then evaluated
      by addressing a standardized questionnaire, QuIC, to trial patients at the three
      intervention hospitals and at control hospitals. Response rate was 90.0% (n =
      288). Of the patients treated by the intervention group, 73% were very satisfied
      with the information received compared with 56% of those of the control group (p
      = 0.003). The patients of the intervention group considered the time given for
      making their decision sufficient more often than those of the controls (98% vs.
      90%, p = 0.004). The patients of the intervention group recalled more often than
      those of the controls that the physician had also offered other therapeutic
      options than the trial treatment (91% vs. 97%, p = 0.032). They also understood
      the main aim of the study better than the patients of the controls (89% vs. 78%,
      p = 0.030). In conclusion, a short communication skills course for the trial
      physicians and nurses improved the quality of informed consent and patient
      satisfaction in the trial.

PMID- 17438706
TI  - Prevalence of Norwegian patients diagnosed with childhood cancer, their working
      ability and need of health insurance benefits.
AB  - The object of this study was in a population-based material to investigate the
      prevalence of patients diagnosed with childhood cancer, and compared to the
      general population to assess working ability, yearly income and need for health
      insurance benefits in patients surviving at least five years after treatment for
      childhood CNS tumours or hematological malignancies. During the period January 1,
      1970 to December 31, 2002 the prevalence in the Norwegian population of patients
      diagnosed with any childhood cancer increased from 12.2 (473/3 888 305) to 65.1
      (2944/4 524 066) per 100 000 population. The proportion of survivors in need of
      any health insurance benefit was for CNS tumours 47.1% and for hematological
      malignancies 21.0%. The proportion in the age group 16-67 receiving disability
      pension for CNS tumours was 94/454 (20.7%) compared to 21/575 (3.7%) for patients
      treated for hematological malignancies (p < 0.001). Of patients given
      radiotherapy 25/70 (35.7%) received disability pension, compared to 90/959 (9.4%)
      in unirradiated patients, p < 0.001. Yearly income and working ability was
      particularly low for CNS tumour survivors. This study illustrates loss of working
      capability associated with pediatric cancer and treatment and long-term
      requirement of health insurance benefits.

PMID- 17438707
TI  - Emotional and behavioral problems in children of parents recently diagnosed with
      cancer: a longitudinal study.
AB  - This study examines the prevalence of problems in children within four months
      after a parent's cancer diagnosis (T1) and six (T2) and twelve months (T3)
      afterwards. Sixty-nine ill parents and 57 spouses completed the Child Behavior
      Checklist for 57 primary school (aged 4-11 years) and 66 adolescent children
      (aged 12-18 years). Adolescents completed the self-report version. Children's
      functioning was compared to that of the norm group and a sample of families that
      were confronted with parental cancer between one to five years before study
      participation (retrospective study). Most children were reported as having a
      similar level as or fewer problems than was reported in the norm and
      retrospective studies. Reported problems decreased with time, but children who
      initially had more problems remained vulnerable during the year. Fathers and
      mothers highly agree in their perception of children's behavior, with the
      exception of adolescent daughters' behavior. Agreement between mothers and
      adolescent daughters was high, whereas agreement between fathers and adolescent
      sons and daughters, and mothers and adolescent sons was low to moderate. The
      outcomes suggest that most children do not experience problems shortly after the
      parent's diagnosis and were functioning over time on a level equal to or better
      than that of their peers. Differences in informant's perceptions appear and
      remain of interest.

PMID- 17438708
TI  - Prospective analysis of quality of life in the first year after colorectal cancer
      surgery.
AB  - Little is known of how the quality of life (QOL) of patients with colorectal
      cancer changes with time following an operation, and whether or not there are
      predictors of QOL after one year in this population. The European Organization
      for Research and Treatment of Cancer QLQ-C30 QOL questionnaire was administered
      to patients before their operation for colorectal cancer, and monthly following
      the operation for up to one year. Multivariate regression analysis was performed
      to examine the predictors of QOL one year after the operation. One hundred
      patients with a mean age of 64 years participated. The scores of five QOL
      dimensions (physical function, role function, fatigue, pain, and dyspnoea)
      dropped significantly below the preoperative values at one month following the
      operation. The scores returned to the preoperative values within three months
      following the operation. The scores of seven QOL dimensions (global QOL,
      emotional function, social function, insomnia, appetite loss, diarrhea, and
      financial difficulties) had improved within three months after the operation.
      Other scores, including cognitive function, nausea and vomiting, and constipation
      remained unchanged. Stepwise regression analyses showed that preoperative
      performance status predicted various QOL scales one year following the operation.
      The overall QOL of colorectal cancer patients became stabilized about three
      months after the operation.

PMID- 17438709
TI  - "Between Men": a psychosocial rehabilitation programme for men with prostate
      cancer.
AB  - The aim of this study was to evaluate the effect of psychosocial rehabilitation
      on newly diagnosed prostate cancer patients. The "Between Men" programme
      consisted of seven weekly sessions of physical training (Phys) alone, information
      (Info) alone or physical training plus information (PhysInfo). After diagnoses,
      patients (n = 211) were consecutively included, stratified and randomised to one
      of four groups: Phys, Info, PhysInfo or standard care control (C). A nurse
      specialised in urology, an urologist and a physiotherapist performed the
      interventions. Patients were followed up during one year with mailed standardised
      questionnaires. It could not be assumed that the "Between Men" programme had any
      effect on patients' anxiety and depression (HADS). Health-related quality of life
      (HRQOL) was associated with stage of disease but not with psychosocial
      intervention. Thus, Physical Function (PF), Role Function (RF) and Fatigue (FA)
      were inferior among patients with, than without, metastases of prostate cancer
      both at baseline and at the 12-month follow-up. This randomized study did not
      demonstrate any significant effect of psychosocial rehabilitation among prostate
      cancer patients. Considering the low rate (1/2), of included/eligible patients a
      less complicated design (intervention versus control) would have been preferred
      in order to increase power.

PMID- 17438710
TI  - Factors associated with return to work after breast cancer treatment.
AB  - Relatively few studies have addressed problems regarding return to work after
      primary treatment for early-stage breast cancer. The purpose of this study was to
      investigate whether socio-economic and treatment-related factors were associated
      with problems of returning to work among pre-menopausal women included in a
      randomized trial of adjuvant endocrine therapy. The duration of all endocrine
      treatments in the trial was two years. At 24 months after randomization 35 of the
      222 recurrence-free patients (16%) had not returned to work. The use of adjuvant
      endocrine therapy was associated with a twofold increase in the odds ratio of not
      having returned to work, although the confidence interval of this ratio was wide
      and included unity. Tumour stage was negatively associated with work status,
      possibly because of its association with adjuvant chemotherapy and radiotherapy
      to the regional nodes. Age and investigated social factors (educational level,
      matrimonial status and presence of under-age children) were not significantly
      associated with return to work. Determining the significance of other social
      factors such as vocational motivation, level of income and vocational
      rehabilitation merits further research.

PMID- 17438711
TI  - The psychometric properties of the Swedish Multidimensional Fatigue Inventory MFI
      20 in four different populations.
AB  - The Multidimensional Fatigue Inventory (MFI-20) scale is widely used for
      measuring fatigue in cancer care. This questionnaire has been translated into
      Swedish and used in Swedish cancer populations, and the aim of this study was to
      test the validity and reliability of the Swedish version in four populations,
      with a total of 584 patients. The participants were classified into four groups:
      palliative cancer patients, cancer patients receiving radiation therapy, non
      cancer outpatients, and a group of hospital staff. The MFI-20 consists of five
      subscales of fatigue: General Fatigue (GF), Physical Fatigue (PF), Reduced
      Motivation (RM), Reduced Activity (RA) and Mental Fatigue (MF). We have tested
      the convergent validity of the MFI-20 using the Category Ratio instrument (CR
      10). The validity and the reliability of MFI-20 were acceptable. All subscales of
      the MFI-20 were correlated, and all were also correlated with the CR-10 score (p
      < or = 0.001). General Fatigue was highly correlated with Physical Fatigue for
      the three patient groups, but this was not the fact for healthy staff. Deleting
      some items increased Cronbach's alpha of the subscale to which these items
      belonged (where alpha measures the reliability of the results). The level of non
      response was low (less than 1.2%) and there was no pattern to the items omitted.
      We conclude that the MFI-20 is a valid and reliable instrument for measuring
      fatigue in patients and in healthy individuals. The results support, to some
      extent, earlier findings and one item can be removed from the Swedish version of
      the MFI-20.

PMID- 17438712
TI  - Dual-isotope lymphoscintigraphy using albumin nanocolloid differentially labeled
      with 111In and 99mTc.
AB  - The aim of this study was to develop and evaluate 111In- and 99mTc-labeled
      derivatives of albumin nanocolloid (NC) for dual-label lymphoscintigraphy to
      allow simultaneous comparison of lymphatic flow from different tissue planes
      draining a tumour bed for accurate identification of sentinel lymph nodes (SLN).
      Using the chelator, p-isothiocyanatobenzyl-1,4,7, 10-tetraazacyclododecane
      1,4,7,10-tetraacetic acid (DOTA), 111In-DOTA-NC and 99mTc-DOTA-NC were compared
      in vitro with respect to stability of labeling, colloidal status and particle
      size, then in vivo by measuring their clearance rates from a subcutaneous
      injection depot. 111In-DOTA-NC and 99mTc-DOTA-NC were indistinguishable on the
      basis of in vitro criteria. Their in vivo clearance rates, however, were
      disparate (0.0015 to 0.075 min(-1) for 111In and 0.0072 to 0.067 min(-1) for
      99mTc), 111In being faster in three studies and markedly slower in three. This
      demonstrates that even when dual-labeled radiotracers behave identically in
      vitro, they will not necessarily do so in vivo. Further work is needed to develop
      dual-labeled NC.

PMID- 17438713
TI  - 111In-pentetreotide scintigraphy in medulloblastoma: a comparison with magnetic
      resonance imaging.
AB  - Medulloblastoma (MB) is a primitive neuroectodermal tumour constituting a grade
      IV brain malignancy. Early and correct detection of recurrence or metastasis is
      desirable for follow-up of patients in this entity. Frequent expression of
      somatostatin receptors by MB lesions facilitates functional tumour imaging by
      somatostatin receptor scintigraphy (SRS). To investigate the value of SRS in the
      follow-up of MB, the results of ten consecutive patients (seven children and
      three adults) undergoing additional imaging with 111In-pentetreotide were
      reviewed. Four, 24 and 48 h p.i. planar and whole body images as well as a SPECT
      study at 4 h p.i. were acquired after intravenous injection of 109 +/- 35 MBq
      111In-pentetreotide (Octreoscan). SRS yielded 11 positive and ten negative
      imaging results, compared to 17 positive and four negative in magnetic resonance
      imaging (MRI). The lesion-by-lesion analysis with a total of 44 lesions revealed
      a sensitivity, specificity, positive predictive value (PPV) and negative
      predictive value (NPV) of 42%, 83%, 94%, 18% for SRS and 89.5%, 50%, 92%, 43% for
      MRI. Based on a per-patient analysis, considering the patient as to be either
      tumour-free or tumour-positive by one imaging modality, the following values for
      sensitivity, specificity, PPV and NPV were obtained: 61%, 100%, 100%, 30% for SRS
      and 94%, 67%, 94%, 67% for MRI. MRI remains the first step imaging technique in
      medulloblastoma patients before and after surgery and during the follow-up
      providing the highest sensitivity. However, to improve specificity and contribute
      to correct diagnosis in MB 111In-pentetreotide scintigraphy should be considered
      as a confirmatory second step imaging tool, especially in case of equivocal MRI
      results. Moreover, a positive SRS scan might serve as a reference before and
      after somatostatin receptor targeted radiotherapy.

PMID- 17438714
TI  - Protein, glucose and lipid metabolism in the cancer cachexia: A preliminary
      report.

PMID- 17438715
TI  - Adrenal insufficiency occurring seven years after nephrectomy for renal cell
      cancer.

PMID- 17438716
TI  - [Hepatic and the portal vein resection in the surgical treatment of
      hepatocellular carcinoma].
AB  - Modern problems of the portal vein resection while hepatectomy performance are
      enlighted. Indications for resection of the portal vein bifurcation zone are
      adduced, various methods of portoplasty are depicted. New methods of the portal
      vein passability restoration in disparity of its sutured parts diameters are
      proposed. The results of hepatectomy combined with portal vein resection are
      studied.

PMID- 17438717
TI  - [Atypical endoscopic papillotomy in diagnostic-treatment algorhythm for
      obstruction of terminal part of the common biliary duct].
AB  - The results of atypical endoscopic papillotomy with subsequent transpapillary
      intervention, performed in the clinic in 2001-2006 for the diagnosis-treatment
      aim in 1090 patients, suffering obstruction of terminal part of common biliary
      duct, were studied. Complications had occurred in 62 (5.7%) patients, bleeding-
      in 34 (3.1%) of them. All the patients had survived.

PMID- 17438718
TI  - [Characteristics of laparoscopic interventions in the patients with calculous
      cholecystitis complicated with hepatic cirrhosis].
AB  - Operative interventions in the patients suffering calculous cholecystitis on the
      hepatic cirrhosis background are accompanied by multiple complications. During
      ten year period laparoscopic cholecystectomy was conducted in the clinics in 138
      patients suffering hepatic cirrhosis. In 12 patients, admitted to the hospital
      for obturation jaundice, endoscopic retrograde cholangiopancreaticography and
      endoscopic papillotomy were primarily done. In 3-7 days after successful removal
      of calculi from the ducts the laparoscopic cholecystectomy was performed. In 39
      (28.3%) of patients complications had occurred, the most frequent of which was
      intraabdominal hemorrhage, as well as gastrointestinal bleeding from the
      varicosely changed esophageal veins in the early postoperative period--in 15
      (10.8%). Two patients died as a consequence of postoperative hemorrhage occurring
      from varicosely changed esophageal veins, developed on the hepatocellular
      insufficiency background.

PMID- 17438719
TI  - [Indices of the external respiratory function in patients suffering from hepatic
      cirrhosis with ascitic syndrome].
AB  - The changes of external respiration indices in the patients suffering hepatic
      cirrhosis, complicated by ascitis and portal hypertension, were studied.
      Application of method of the ascitic liquor extracorporeal ultrafiltration and
      sorption with its subsequent return into venous system was proposed. The
      morphological changes of pulmonary parenchyma, which coincided with lowering of
      the external respiration indices in the patients, were studied.

PMID- 17438720
TI  - [The choice of surgical tactics in complicated forms of hepatic echinococcosis].
AB  - Surgical tactics in complicated forms of hepatic echinococcosis was proposed,
      basing on the analysis of surgical treatment results, obtained in 378 patients
      suffering this disease. The method of biliary fistula closure, using the flap,
      modelled of fibrous capsule of echinococcal cyst was elaborated. The trapeziform
      flap was modelled from fibrous capsule after performance of conventional
      echinococcectomy. The sutures were put on the fistula aperture edges along its
      circumference 2-3 mm each other apart and to them the flap apex was sutured. On
      completion of the sutures tying the fistula aperture was closed alike with
      hermetic patch.

PMID- 17438721
TI  - [Clinical, morphological, and microbiological characteristics of the Mallory
      Weiss syndrome].
AB  - The profound clinico-morphological and immunological analysis was performed in
      patients suffering Mallory-Weiss syndrome (MWS). Doing endoscopic and
      morphological investigations the most dangerous foci of the affection were
      revealed and there links with the disease course severity and the recurrences
      rate established. The signs of unstable haemostasis were revealed according to
      the endoscopic investigation data. Morphological changes of gastric mucosa in
      patients suffering MWS are similar to those in duodenal ulcer disease.
      Polymorphism of mucosal microorganisms with E. coli, Streptococcus beta
      haemoliticus, Klebsiella pneumoniae, Candida albicans predominance, which severe
      the disease course and cause the haemorrhage recurrence, was characteristic for
      MWS in 85% of observations. These causing agents are sensitive to II-III
      generation cephalosporins and fluoroquinolons in 75% of observations. The complex
      of conservative treatment must include, besides restorational, untiulcer,
      antihelicobacter and antibacterial therapy.

PMID- 17438722
TI  - [Effect of the biliary decompression method on the postoperative period course in
      patients suffering from obturation jaundice].
AB  - The changes of markers of the systemic inflammatory answer syndrome, depending on
      the biliary decompression method applied, were studied in 231 patients, operated
      on for obturation jaundice.

PMID- 17438723
TI  - [Surgical methods in the treatment of pancreatic pseudocysts].
AB  - The results of treatment of 209 patients suffering pancreatic pseudocysts are
      adduced. The pseudocyst maturity degree determines the method of treatment
      choice. Optimal combination of conservative and the puncture methods constitute
      the main principle of treatment of acute pancreatic pseudocysts.

PMID- 17438724
TI  - [Using ultrasonography in the diagnosis and treatment of pancreatic cancer].
AB  - The results of miniinvasive interventions under the ultrasonographic control,
      performed in 125 patients suffering pancreatic cancer, were analyzed. Trepan
      biopsy of pancreatic gland was applied in preoperative examination algorhythm.
      The biliary ducts transcutaneous transhepatic decompression application had
      permitted to increase the frequency of the elective radical operations
      performance, to lower the general and postoperative mortality rate (from 23.3 to
      6.5%) as well as the frequency of early postoperative complications (from 12.4 to
      6.8%).

PMID- 17438725
TI  - [Application of cava-filter for surgical prophylaxis of pulmonary
      thromboembolism].
AB  - Results of treatment of 148 patients, in whom deep veins thrombosis of v. cava
      inferior (VCI) system had occurred, were analyzed. Cava-filter (CF) was applied
      in 50 patients. CF "Osot" and temporary CF-thrombextractor were implanted for
      pulmonary thromboembolism (PTE) prophylaxis. Temporary CF-thrombextractors were
      implanted in 41 (66%) patients, the current CF "Osot"--in 21 (44%), the temporary
      one "Osot"--in 21 (44%), temporary CF with subsequent change for current one--in
      12 (19%). The PTE recurrence was not observed, the VCI thrombosis had occurred
      after CF implantation in 3.2% of observations.

PMID- 17438726
TI  - [Comparison of surgical treatment efficacy in patients with complex
      extrasphincteric rectal fistulas using principal operative methods].
AB  - We have analyzed results of treatment of 211 patients with complex
      extrasphincteric rectal fistulas. We have used the different methods of
      treatment, in particular, method of Ryzhih, method of "integrated" block and
      method of "packing" rectal fistulas using autothrombin glue. Estimation of
      results was based on two main criteria: the postoperative relapses rate and
      postoperative incontinence rate. The method of "integrated" block and the method
      of "packing" of rectal fistulas using autothrombin glue give less postoperative
      relapses rate and the incontinence rate en immediate and remote period after
      intervention.

PMID- 17438727
TI  - [Changes of acid-producing function of the stomach before and after operation
      performed for gastric ulcer type I].
AB  - The gastric acid-producing function changes were analyzed in 48 patients
      suffering gastric ulcer (Johnson-I type), using the computer pH-metry. The
      dependence of the gastric glands acid-production on the ulcer defect localization
      was established. Hyperchlorhydria was revealed in 84.6% of patients suffering
      gastric distal third ulcer and in its subcardial localization--in 30.8%. In the
      late follow-up period after the operation, performed for gastric ulcer disease,
      the gastric stump capacity to restore its glands production of acid depends
      mainly on the method of surgical procedure applied. The best indices were
      revealed after application of organpreserving method--the partial resection of
      gastric ischemized segment according to L. Ya. Kovahlchuk combined with selective
      proximal vagotomy, comparing with such after application of resectional methods
      according to Billroth.

PMID- 17438728
TI  - [First experience of the hip joint prosthesis using DePuy ASR system].
AB  - The system of the hip joint total endoprosthesis DePuy owes undoubted advantages
      over standard metal-polymer systems and constitutes the optimal one on the modern
      stage of endoprosthesis development for young patients, it permits to escape the
      revision prosthesis. Early return of the patients to labour activity and short
      period of adaptation constitute economical efficacy of the construction applied.

PMID- 17438729
TI  - [Changes of biochemical content of the duodenal mucosa in early recurrence of
      bleeding].
AB  - Using the duodenal bleeding and its early recurrence modelling on 48 mongrel dogs
      the dynamics of content of general protein, urea and glucose in duodenal mucosa
      were investigated. There was established that the dynamics of investigated
      indices of anterior and posterior duodenal wall appeared different and that the
      level of urea while early recurrence of duodenal bleeding owes consistent
      tendency for lowering, especially in posterior duodenal wall. The glucose level
      in these both walls is merely stable.

PMID- 17438730
TI  - [Reconstruction of the arteries in the femoro-popliteal segment in the leg large
      subcutaneous vein insufficiency].

PMID- 17438731
TI  - [Method of fastening of the treatment apparatus on the sternocostal frame].

PMID- 17438732
TI  - [The method of the common biliary duct plasty for partial excision of its
      anterior wall during cholecystectomy].

PMID- 17438733
TI  - [Not Available].

PMID- 17438734
TI  - [Not Available].

PMID- 17438735
TI  - [Not Available].

PMID- 17438736
TI  - [Not Available].

PMID- 17438737
TI  - [Not Available].

PMID- 17438738
TI  - [Not Available].

PMID- 17438739
TI  - [Not Available].

PMID- 17438740
TI  - [Not Available].

PMID- 17438741
TI  - [Not Available].

PMID- 17438742
TI  - [Not Available].

PMID- 17438743
TI  - [Not Available].

PMID- 17438744
TI  - More triclosan trouble.

PMID- 17438745
TI  - Indoor air is a major source of PCBs.

PMID- 17438746
TI  - Closing the phosphorus loop.

PMID- 17438747
TI  - What history can teach us about the future costs of U.S. nuclear power.

PMID- 17438748
TI  - Photochemical modeling of emissions trading of highly reactive volatile organic
      compounds in Houston, Texas. 1. Reactivity based trading and potential for ozone
      hot spot formation.
AB  - As part of the State Implementation Plan for attaining the National Ambient Air
      Quality Standard for ozone, the Texas Commission of Environmental Quality has
      created a Highly Reactive Volatile Organic Compounds (HRVOC) Emissions Cap and
      Trade Program for industrial point sources in the Houston/Galveston/Brazoria
      area. This program has a number of unique features, including its focus on a
      limited group of ozone precursors and its provisions for trading emissions based
      on atmospheric reactivity. This series of papers examines the potential air
      quality impacts of this new emission trading program through photochemical
      modeling of potential trading scenarios; this first paper in the series describes
      the air quality modeling methods used to assess potential trades, the potential
      for localized increases in ozone concentrations (ozone "hot spots") due to HRVOC
      emission trading, and the use of reactivity scales in the trading. When HRVOC
      emissions are traded on a mass basis, the simulations indicate that trading of
      HRVOC allowances between facilities resulted in less than 0.15 ppb (<0.13%) and
      0.06 ppb (<0.06%) increases in predicted maximum, area-wide 1-h averaged and 8-h
      averaged ozone concentrations, respectively. Maximum decreases in ozone
      concentrations associated with trading, as opposed to across-the-board
      reductions, were larger than the increases. All of these changes are small
      compared to the maximum changes in ozone concentrations due to the VOC emissions
      from these sources (up to 5-10 ppb for 8 h averages; up to 30 ppb for 1-h
      averages). When emissions of HRVOCs are traded for other, less reactive
      emissions, on a reactivity weighted basis, air quality simulations indicate that
      daily maximum ozone concentrations increased by less than 0.3%. Because these
      relatively small changes (< 1%) are for unlikely trading scenarios designed to
      produce a maximum change in ozone concentrations (all emissions traded into
      localized regions), the simulations indicate that the implementation of the
      trading program, as currently configured and possibly expanded, is unlikely to
      cause localized increases in ozone concentrations ("hot spots").

PMID- 17438749
TI  - Photochemical modeling of emissions trading of highly reactive volatile organic
      compounds in Houston, Texas. 2. Incorporation of chlorine emissions.
AB  - As part of the State Implementation Plan for attaining the National Ambient Air
      Quality Standard for ozone, the Texas Commission of Environmental Quality has
      created a Highly Reactive Volatile Organic Compounds (HRVOC) Emissions Cap and
      Trade Program for industrial point sources in the Houston/Galveston/Brazoria
      area. This series of papers examines the potential air quality impacts of this
      new emission trading program through photochemical modeling of potential trading
      scenarios; this paper examines the air quality impact of allowing facilities to
      trade chlorine emission reductions for HRVOC allocations on a reactivity weighted
      basis. The simulations indicate that trading of anthropogenic chlorine emission
      reductions for HRVOC allowances at a single facility or between facilities, in
      general, resulted in improvements in air quality. Decreases in peak 1-h averaged
      and 8-h averaged ozone concentrations associated with trading chlorine emissions
      for HRVOC allocations on a Maximum Incremental Reactivity (MIR) basis were up to
      0.74 ppb (0.63%) and 0.56 ppb (0.61%), respectively. Air quality metrics based on
      population exposure decreased by up to 3.3% and 4.1% for 1-h and 8-h averaged
      concentrations. These changes are small compared to the maximum changes in ozone
      concentrations due to the VOC emissions from these sources (5-10 ppb for 8-h
      averages; up to 30 ppb for 1-h averages) and the chlorine emissions from the
      sources (5-10 ppb for maximum concentrations over wide areas and up to 70 ppb in
      localized areas). The simulations indicate that the inclusion of chlorine
      emissions in the trading program is likely to be beneficial to air quality and is
      unlikely to cause localized increases in ozone concentrations ("hot spots").

PMID- 17438750
TI  - Population level impacts of cooling water withdrawals on harvested fish stocks.
AB  - Trillions of gallons are withdrawn every year from U.S. rivers, estuaries, lakes,
      and coastal waters to cool the turbines of power plants and other equipment in
      manufacturing facilities. In the process, large numbers of aquatic organisms die
      from entrainment into the plant or impingement against the outer portion of the
      intake structure. In this paper, we develop a generalized age-structured
      population model with density dependent survival of sub-adult age classes, and we
      use the model to perform a screening analysis of the effects of entrainment and
      impingement for 15 harvested fish stocks off the California and Atlantic coasts.
      Stock sizes are estimated to be depressed by entrainment and impingement by less
      than 1% in 10 of the 15 cases considered, between 1 and 3% in two cases, and
      between 20 and 80% in three cases. A variety of sensitivity analyses are
      conducted to evaluate the influence of several sources of model and parameter
      uncertainties.

PMID- 17438751
TI  - Emissions of levoglucosan, methoxy phenols, and organic acids from prescribed
      burns, laboratory combustion of wildland fuels, and residential wood combustion.
AB  - Biomass combustion emissions make a significant contribution to the overall
      particulate pollution in the troposphere. Wildland or prescribed burns and
      residential wood combustion emissions can vary due to differences in fuel,
      season, time of day, and the nature of the combustion. Inadequate understanding
      of the relevance of these biomass combustion emissions is due to the lack of
      characterization of open combustion emissions and the limited understanding of
      the differences between these and residential wood combustion. To provide new
      insight to biomass combustion emissions, sampling was conducted in several types
      of conditions. Semi-volatile organic compounds (SVOC) were collected during four
      separate prescribed burns in three different ecosystems, Mariposa Sequoia Grove
      within Yosemite National Park, CA, desert brushes of central rural Nevada, and
      Toiyabye National Forest near Lake Tahoe, NV. SVOC samples were also collected
      under controlled conditions for several wildland fuels, including conifer
      needles, wildland grasses, and sagebrush. Fireplace emissions from simulated
      residential wood combustion were also collected and are included here for
      comparison. A high degree of variability was found in the emissions of organic
      carbon, elemental carbon, levoglucosan, methoxy phenols, and organic acids. The
      variability in the emissions of levoglucosan does not correlate with the PM2.5
      gravimetric mass and thus may affect source apportionment estimates.

PMID- 17438752
TI  - Factors associated with sources, transport, and fate of volatile organic
      compounds and their mixtures in aquifers of the United States.
AB  - Factors associated with sources, transport, and fate of volatile organic
      compounds (VOCs) in groundwater from aquifers throughout the United States were
      evaluated using statistical methods. Samples were collected from 1631 wells
      throughout the conterminous United States between 1996 and 2002 as part of the
      National Water-Quality Assessment (NAWQA) Program of the U.S. Geological Survey.
      Water samples from wells completed in aquifers used to supply drinking water were
      analyzed for more than 50 VOCs. Wells were primarily rural domestic water
      supplies (1184), followed by public water supplies (216); the remaining wells
      (231) supplied a variety of uses. The median well depth was 50 meters. Age-date
      information shows that about 60% of the samples had a fraction of water recharged
      after 1953. Chloroform, toluene, 1,2,4-trimethyl-benzene, and perchloroethene
      were some of the frequently detected VOCs. Concentrations generally were less
      than 1 microg/L. Source factors include, in order of importance, general land-use
      activity, septic/sewer density, and sites where large concentrations of VOCs are
      potentially released, such as leaking underground storage tanks. About 10% of all
      samples had VOC mixtures that were associated with concentrated sources; 20% were
      associated with dispersed sources. Important transport factors included
      well/screen depth, precipitation/groundwater recharge, air temperature, and
      various soil characteristics. Dissolved oxygen was strongly associated with VOCs
      and represents the fate of many VOCs in groundwater. Well type (domestic or
      public water supply) was also an important explanatory factor. Results of
      multiple analyses show the importance of (1) accounting for both dispersed and
      concentrated sources of VOCs, (2) measuring dissolved oxygen when sampling wells
      to help explain the fate of VOCs, and (3) limiting the type of wells sampled in
      monitoring networks to avoid unnecessary variance in the data, or controlling for
      this variance during data analysis.

PMID- 17438753
TI  - Atmospheric methane: trends and cycles of sources and sinks.
AB  - For more than 20 years the global emissions and the lifetime of methane have
      probably been constant, so the buildup of methane in the atmosphere has been
      slowing down for as long. During this time, there have been periodic events
      occurring every seven to eight years, when global methane concentrations
      increased by some 10 ppb and later fell back, in some cases due to temporary
      increases of emissions from the northern tropics that spread to the global scale.
      These conclusions are derived from the accumulated global observations that now
      span 23 years and define the role of human activities in the recent cycle of
      atmospheric methane.

PMID- 17438754
TI  - In-cabin commuter exposure to ultrafine particles on Los Angeles freeways.
AB  - Worldwide people are exposed to toxic ultrafine particles (UFP, with diameters
      (dp) less than 100 nm) and nanoparticles (NP, dp < 50 nm) under a variety of
      circumstances. To date, very limited information is available on human exposure
      to freshly emitted UFP and NP while traveling on major roads and freeways. We
      report in-cabin and outdoor measurements of particle number concentration and
      size distributions while driving three vehicles on Los Angeles freeways. Particle
      number concentrations and size distributions were measured under different
      vehicle ventilation settings. When the circulation fan was set to on, with
      substantial external air intake, outside changes in particle counts caused
      corresponding in-cabin changes approximately 30-60 s later, indicating an maximal
      air exchange rate of about 120-60 h(-1). Maximum in-cabin protection
      (approximately 85%) was obtained when both fan and recirculation were on. In
      cabin and outdoor particle size distributions in the 7.9-217 nm range were
      observed to be mostly bimodal, with the primary peak occurring at 10-30 nm and
      the secondary at 50-70 nm. The vehicle's manufacture-installed particle filter
      offered an in-cabin protection of about 50% for particles in the 7-40 nm size
      range and 20-30% for particles in the 40 to approximately 200 nm size range. For
      an hour daily commute exposure, the in-vehicle microenvironment contributes
      approximately 10-50% of people's daily exposure to UFP from traffic.

PMID- 17438755
TI  - Arsenic and manganese contamination of drinking water resources in Cambodia:
      coincidence of risk areas with low relief topography.
AB  - Arsenic contamination of groundwater has been identified in Cambodia, where some
      100,000 family-based wells are used for drinking water needs. We conducted a
      comprehensive groundwater survey in the Mekong River floodplain, comprising an
      area of 3700 km(2) (131 samples, 30 parameters). Seasonal fluctuations were also
      studied. Arsenic ranged from 1 to 1340 microg L(-1) (average 163 microg L(-1)),
      with 48% exceeding 10 microg L(-1). Elevated manganese levels (57% >0.4 mg L(-1))
      are posing an additional health threat to the 1.2 million people living in this
      area. With 350 people km(-2) potentially exposed to chronic arsenic poisoning,
      the magnitude is similar to that of Bangladesh (200 km(-2)). Elevated arsenic
      levels are sharply restricted to the Bassac and Mekong River banks and the
      alluvium braided by these rivers (Kandal Province). Arsenic in this province
      averaged 233 microg L(-1) (median 100 microg L(-1)), while concentrations to the
      west and east of the rivers were <10 microg L(-1). Arsenic release from Holocene
      sediments between the rivers is most likely caused by reductive dissolution of
      metal oxides. Regions exhibiting low and elevated arsenic levels are co-incident
      with the present low relief topography featuring gently increasing elevation to
      the west and east of a shallow valley-understood as a relict of pre-Holocene
      topography. The full georeferenced database of groundwater analysis is provided
      as Supporting Information.

PMID- 17438756
TI  - Concentrations and chiral signatures of polychlorinated biphenyls in outdoor and
      indoor air and soil in a major U.K. conurbation.
AB  - Concentrations and chiral signatures of polychlorinated biphenyls (PCBs) were
      measured in outdoor air (using polyurethane foam (PUF)--disk passive samplers)
      and surface soil samples taken at approximately monthly intervals over 1 year at
      10 locations on a rural-urban transect across the West Midlands of the U.K. In
      both air and soil, concentrations clearly decrease with increasing distance from
      the city center, supporting the existence of an urban "pulse", that indicate the
      West Midlands conurbation to be a source of PCBs to the wider environment.
      Concentrations of PCBs in outdoor air samples in this study are well below those
      reported previously for indoor air in the West Midlands. This, combined with
      comparison of chiral signatures in outdoor air and soil with those in samples of
      indoor air taken in the West Midlands, suggest strongly that the principal
      contemporary source of PCBs in this conurbation is ventilation of indoor air and
      not volatilization from soil. Future reductions in PCB concentrations in outdoor
      air and ultimately human exposure appear best achieved by action to remove
      remaining sources of PCBs from existing structures.

PMID- 17438757
TI  - Inland subsurface water system role for coastal nitrogen load dynamics and
      abatement responses.
AB  - We simulate and analyze long-term dynamics of coastal nitrogen (N) loading and
      the inland source changes and processes that may have determined its development
      over the past 60-year period and may govern its possible future responses to
      various N source management scenarios. With regard to processes, the results show
      that average basin-scale N delivery fractions to the coast may not be
      representative of the coastal impacts of either diffuse or point inland sources.
      The effects of inland source changes may be greatly redistributed in space-time
      and delayed by slow N transport and mass transfer processes in the subsurface
      water system of coastal catchments. Extrapolation of current N transport
      attenuation conditions for quantification of future abatement effects may
      therefore be misleading if the extrapolation models do not realistically
      represent delayed long-term influences of slow subsurface processes. With regard
      to policy, the results show that and why national Swedish and international
      Baltic Sea region policies for coastal N load abatement may be difficult or
      impossible to achieve by inland source abatement only. Large mitigation of both
      point and diffuse sources may be necessary to achieve targeted coastal N load
      reductions fast and maintain them also in the long term.

PMID- 17438758
TI  - Coupling passive air sampling with emission estimates and chemical fate modeling
      for persistent organic pollutants (POPs): a feasibility study for Northern
      Europe.
AB  - Passive air samplers (polyurethane foam disks) were deployed at 23 background
      locations along a broadly west-east transect in 8 northern European countries and
      analyzed for PCBs, PBDEs, PAHs, and a range of organochlorine pesticides (HCB,
      DDTs, and DDEs). PCBs and PAHs were highest at the center of the transect
      (Denmark) and lowest in northern Norway. HCB was relatively uniformly
      distributed, reflecting its persistence and high degree of mixing in air. Higher
      DDE and DDT levels occurred in Eastern Europe and at several sites in Central
      Europe. PBDE levels were generally similar at all sites, but lower for some
      locations in Eastern Europe and Ireland. Emissions information for PCBs, HCB, and
      PBDEs was used as input for a multi-media chemical fate model, to generate
      predicted air concentrations and compare with these measured values. Different
      scenarios were highlighted by this exercise: (i) country and compound
      combinations where the national inventory gave predicted air concentrations in
      close agreement with those measured (e.g., PCBs in the UK); (ii) country and
      compound combinations where predicted concentrations were well below those
      measured, but where advection of emissions from elsewhere is likely to be
      important (e.g., PCBs in Norway); (iii) consistent underestimation of compound
      concentrations by the emissions modeling (i.e., HCB); and (iv) general
      overestimation of ambient concentrations (i.e., PBDEs). Air mass trajectory
      analysis showed the likely role of long-range atmospheric transport (LRAT) on
      national levels. In general, advection from the south and west of Europe appeared
      to contribute to ambient POPs levels for countries in the center and northeast of
      the transect. Guidelines are presented as to how countries that want to assess
      their POPs source inventories can do so with this relatively cheap initial
      screening approach.

PMID- 17438759
TI  - Vertical and temporal distribution of persistent organic pollutants in Toronto.
      1. Organochlorine pesticides.
AB  - From May to September 2005, five passive air samples were deployed over five, 1
      month periods at five elevations on the CN Tower in Toronto, Canada, to
      investigate the vertical distribution, seasonality, and sources of organochlorine
      pesticides. A strong seasonality was observed between spring and the end of
      summer. Vertical profiles differed for different pesticide classes. For instance,
      alpha- and gamma-hexachlorocyclohexane exhibited higher concentrations (60-80 pg
      m(-3), respectively) near the ground during the spring and early summer,
      suggesting that surface-air exchange within the city or nearby Lake Ontario may
      be important sources. The vertical profile for chlordane isomers was variable,
      suggesting that both advective and local inputs are important. For dieldrin, no
      obvious trend with elevation was observed, suggesting that concentrations could
      reflect a regional air mass contamination. Strongest seasonality was observed for
      the endosulfans, a widely used pesticide in North America, that reached peak
      concentrations of 750-850 pg m(-3) during June/July. Advective inputs of
      endosulfan from regional or more distant agricultural regions can explain the
      relatively uniform concentrations with elevation throughout the study period. The
      approach used in this study demonstrates that monthly average vertical
      concentration profiles differ between pesticide groups and reflect their use as
      well as the relative magnitude of input from local versus regional sources.

PMID- 17438760
TI  - Market basket survey shows elevated levels of As in South Central U.S. processed
      rice compared to California: consequences for human dietary exposure.
AB  - We report the largest market basket survey of arsenic (As) in U.S. rice to date.
      Our findings show differences in transitional-metal levels between polished and
      unpolished rice and geographical variation in As and selenium (Se) between rice
      processed in California and the South Central U.S. The mean and median As grain
      levels for the South Central U.S. were 0.30 and 0.27 mimcrog As g(-1),
      respectively, for 107 samples. Levels for California were 41% lower than the
      South Central U.S., with a mean of 0.17 microg As g(-1) and a median of 0.16
      microg As g(-1) for 27 samples. The mean and median Se grain levels for the South
      Central U.S. were 0.19 microg Se g(-1). Californian rice levels were lower,
      averaging only 0.08 and 0.06 microg Se g(-1) for mean and median values,
      respectively. The difference between the two regions was found to be significant
      for As and Se (General Linear Model (GLM): As p < 0.001; Se p < 0.001). No
      statistically significant differences were observed in As or Se levels between
      polished and unpolished rice (GLM: As p= 0.213; Se p= 0.113). No significant
      differences in grain levels of manganese (Mn), cobalt (Co), copper (Cu), or zinc
      (Zn) were observed between California and the South Central U.S. Modeling arsenic
      intake for the U.S. population based on this survey shows that for certain groups
      (namely Hispanics, Asians, sufferers of Celiac disease, and infants) dietary
      exposure to inorganic As from elevated levels in rice potentially exceeds the
      maximum intake of As from drinking water (based on consumption of 1 L of 0.01 mg
      L(-1) In. As) and Californian state exposure limits. Further studies on the
      transformation of As in soil, grain As bioavailability in the human
      gastrointestinal tract, and grain elemental speciation trends are critical.

PMID- 17438761
TI  - Atmospheric trends and radiative forcings of CF4 and C2F6 inferred from firn air.
AB  - The atmospheric histories of two potent greenhouse gases, tetrafluoromethane
      (CF4) and hexafluoroethane (C2F6), have been reconstructed for the 20th century
      based on firn air measurements from both hemispheres. The reconstructed
      atmospheric trends show that the mixing ratios of both CF4 and C2F6 have
      increased during the 20th century by factors of approximately 2 and approximately
      10, respectively. Initially, the increasing mixing ratios coincided with the rise
      in primary aluminum production. However, a slower atmospheric growth rate for CF4
      appears to be evident during the 1990s, which supports recent aluminum industry
      reports of reduced CF4 emissions. This work illustrates the changing relationship
      between CF4 and C2F6 that is likely to be largely the result of both reduced
      emissions from the aluminum industry and faster growing emissions of C2F6 from
      the semiconductor industry. Measurements of C2F6 in the older firn air indicate a
      natural background mixing ratio of <0.3 parts per trillion (ppt), demonstrating
      that natural sources of this gas are negligible. However, CF4 was deduced to have
      a preindustrial mixing ratio of 34 -1 ppt (-50% of contemporary levels). This is
      in good agreement with the previous work of Harnisch et al. (18) and provides
      independent confirmation of their results. As a result of the large global
      warming potentials of CF4 and C2F6, these results have important implications for
      radiative forcing calculations. The radiative forcings of CF4 and C2F6 are shown
      to have increased over the past 50 years to values in 2001 of 4.1 x 10(-3) Wm(-2)
      and 7.5 x 10(-4) Wm(-2), respectively, relative to preindustrial concentrations.
      These forcings are small compared to present day forcings due to the major
      greenhouse gases but, if the current trends continue, they will continue to
      increase since both gases have essentially infinite lifetimes. There is,
      therefore, a large incentive to reduce perfluorocarbon emissions such that
      through the implementation of the Kyoto Protocol, the atmospheric growth rates
      may decline in the future.

PMID- 17438762
TI  - Reaction of polycyclic aromatic hydrocarbons adsorbed on silica in aqueous
      chlorine.
AB  - The reaction of polycyclic aromatic hydrocarbons (PAHs) previously adsorbed on
      silica gel or diatomaceous earth with sodium hypochlorite was carried out to
      elucidate their reactivity to aqueous chlorine. It was demonstrated that the PAHs
      adsorbed on silica reacted more rapidly than the PAHs themselves in water,
      leading to the formation of many chlorinated and oxidized derivatives. A similar
      reaction in the presence of potassium bromide was found to preferentially produce
      corresponding brominated derivatives. These reactions seem to proceed through
      PAHs adsorbed on the silica surface and halogenating agents, the electrophilicity
      of which may be raised by the catalytic effect of the silanol group of the silica
      surface. These findings from the environmental viewpoint suggest that the
      reaction of hydrophobic compounds adsorbed on sediment cannot be neglected.

PMID- 17438763
TI  - Altitudinal gradients of PBDEs and PCBs in fish from European high mountain
      lakes.
AB  - A first case of temperature-dependent distribution of polybromodiphenyl ethers
      (PBDEs) in remote areas is shown. Analysis of these compounds in fish from
      Pyrenean lakes distributed along an altitudinal transect shows higher
      concentrations at lower temperatures, as predicted in the global distillation
      model. Conversely, no temperature-dependent distribution is observed in a similar
      transect in the Tatra mountains (Central Europe) nor in fish from high mountain
      lakes distributed throughout Europe. The fish concentrations of
      polychlorobiphenyls (PCBs) examined for comparison showed significant temperature
      correlations in all these studied lakes. Cold trapping of both PCBs and PBDEs
      concerned the less volatile congeners. In the Pyrenean lake transect the
      concentrations of PCBs and PBDEs in fish were correlated despite the distinct use
      of these compounds and their 40 year time lag of emissions to the environment.
      Thus, temperature effects have overcome these anthropogenic differences
      constituting at present the main process determining their distributions. These
      cases of distinct PBDEs and PCBs behavior in high mountains likely reflect early
      stages in the environmental distribution of the former since they have been under
      secondary redistribution processes over much shorter time than the latter.

PMID- 17438764
TI  - Beach sand and sediments are temporal sinks and sources of Escherichia coli in
      Lake Superior.
AB  - The Duluth Boat Club (DBC) Beach, located in the Duluth-Superior harbor of Lake
      Superior, is frequently closed in summer due to high counts of Escherichia coli,
      an indicator of fecal contamination. However, the sources of bacteria
      contributing to beach closure are currently unknown. In this study, we
      investigated the potential sources of E. coli contaminating the DBC beach by
      using modified rep-PCR (HFERP) DNA fingerprinting. Over 3600 E. coli strains were
      obtained from 55 lake water, 25 sediment, and 135 sand samples taken from five
      transects at the DBC beach at 11 different times during the summer through fall
      months of 2004 and 2005. Potential sources of E. coli at this beach were
      determined by using a known-source DNA fingerprint library containing unique E.
      coli isolates from wildlife, waterfowl, and treated wastewater obtained near
      Duluth, MN. Amounts E. coli in the samples were enumerated by membrane filtration
      counting, and the presence of potentially pathogenic E. coli was determined by
      using multiplex PCR. E. coli counts in all samples increased during the summer
      and early fall (Julyto September). While E. coli in spring samples originated
      mainly from treated wastewater effluent, the percentage of E. coli from waterfowl
      increased from summer to fall. DNA fingerprint analyses indicated that some E.
      coli strains may be naturalized, and autochthonous members of the microbial
      community in the beach sand and sediments were examined. However, multiplex PCR
      results indicated that <1% of the E. coli strains at the DBC was potentially
      pathogenic. Our results also suggest that wave action may influence the early
      colonization and homogeneous distribution of E. coli in beach sand and the
      subsequent release of sand or sediment-borne E. coli into lake water. Taken
      together, these results indicate that sand and sediment serve as temporal sources
      and sinks of human and waterfowl-derived E. coli that contribute to beach
      closures.

PMID- 17438765
TI  - PCDD/F contamination over time in Japanese paddy soils.
AB  - Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs)were analyzed in
      preserved paddy soils periodically collected from 7 sites around Japan since 1960
      to trace the changes in concentrations, to elucidate their sources, and to
      estimate their mass balance in Japanese paddy fields. Concentrations of sigma
      PCDD/Fs in paddy soils from all sites increased during the 1960s and the 1970s,
      then decreased. The results of principal component analysis and chemical mass
      balance based on functional relationship analysis indicate that the increase in
      sigma PCDD/F concentrations in paddy soils was due to the increased use of
      pentachlorophenol (PCP) and chlornitrofen (CNP); more than 95% of PCDD/Fs in all
      paddy soils were derived from impurities in these herbicides. The half-lives of
      PCDD/F for disappearance from the paddy soils were estimated to be 10 to 20 years
      (mean: 17.3 years). The estimated PCDD/F mass balance using the above half-life
      during the past 40 years in paddy fields indicates that about 80% of PCDD/Fs have
      disappeared. The soil puddling (mechanically mixing of paddy soil with pooled
      irrigation water) is implied as one reason for the PCDD/F disappearance from
      paddy fields. However, as the amounts of PCDD/Fs added through the use of PCP and
      CNP were extremely large, PCDD/F concentrations in Japanese paddy soils will
      decrease gradually, and PCDD/F runoff from paddy fields to surrounding catchments
      will continue.

PMID- 17438766
TI  - Bioaccumulation, temporal trend, and geographical distribution of synthetic musks
      in the marine environment.
AB  - Bioaccumulation of synthetic musks in a marine food chain was investigated by
      analyzing marine organisms at various trophic levels, including lugworm, clam,
      crustacean, fish, marine mammal, and bird samples collected from tidal flat and
      shallow water areas of the Ariake Sea, Japan. Two of the polycyclic musks, HHCB
      and AHTN, were the dominant compounds found in most of the samples analyzed,
      whereas nitro musks were not detected in any of the organisms, suggesting greater
      usage of polycyclic musks relative to the nitro musks in Japan. The highest
      concentrations of HHCB were detected in clams (258-2730 ng/g lipid wt.), whereas
      HHCB concentrations in mallard and black-headed gull were low, and comparable
      with concentrations in fish and crab. These results are in contrast to the
      bioaccumulation pattern of polychlorinated biphenyls; for which a positive
      correlation between the concentration and the trophic status of organisms was
      found. Such a difference in the bioaccumulation is probably due to the metabolism
      and elimination of HHCB in higher trophic organisms. Temporal trends in
      concentrations of synthetic musks were examined by analyzing tissues of marine
      mammals from Japanese coastal waters collected during 1977-2005. HHCB
      concentrations in marine mammals have shown significant increase since the early
      1990s, suggesting a continuous input of this compound into the marine
      environment. Comparison of the time trend for HHCB with those for PCBs and PBDEs
      suggested that the rates of increase in HHCB concentrations were higher than the
      other classes of pollutants. To examine the geographical distribution of HHCB, we
      have analyzed tissues of fish, marine mammals, and birds collected from several
      locations. Synthetic musks were not detected in a sperm whale (pelagic species)
      from Japanese coastal water and in eggs of south polar skua from Antarctica.
      While the number of samples analyzed is limited, these results imply a lack of
      long-range transportation potential of synthetic musks in the environment.

PMID- 17438767
TI  - Particle concentration and Characteristics near a major freeway with heavy-duty
      diesel traffic.
AB  - This study presents the number, surface and volume concentrations, and size
      distribution of particles next to the 1-710 freeway during February through April
      2006. 1-710 has the highest ratio (up to 25%) of heavy-duty diesel vehicles in
      the Los Angeles highway network. Particle concentration measurements were
      accompanied by measurements of black carbon, elemental and organic carbon, and
      gaseous species (CO, CO2). Using the incremental increase of CO2 over the
      background to calculate the dilution ratio, this study makes it possible to
      compare particle concentrations measured next to the freeway to concentrations
      measured in roadway tunnels and in vehicle exhaust. In addition to the effect of
      the dilution ratio on the measured particle concentrations, multivariate linear
      regressions showed that light and heavy organic carbon concentrations are
      positively correlated with the particle volume in the nucleation and accumulation
      modes, respectively. Solar radiation was also positively correlated with the
      particle surface concentration and the particle volume in the accumulation (40
      638 nm) mode, presumably as a result of secondary particle formation. The methods
      developed in this study may be used to decouple the effect of sampling position,
      meteorology, and fleet operation on particle concentrations in the proximity of
      freeways, roadway tunnels, and in street canyons.

PMID- 17438768
TI  - Surface irrigation reduces the emission of volatile 1,3-dichloropropene from
      agricultural soils.
AB  - Low-cost, practicable techniques are required to limit the release of volatile
      organic compound-containing fumigants such as 1,3-D to the atmosphere. In this
      study, we aimed to quantify 1,3-D diffusion and emission from laboratory soil
      columns maintained under realistic conditions and thereby assess the efficacy of
      soil irrigation as a technique for reducing emissions. In two soils (one
      relatively high, and one relatively low, in organic matter), irrigation led to a
      limiting of upward diffusion of the fumigant and to the maintenance of higher
      soil gas concentrations. Therefore, rather than being emitted from the column,
      the 1,3-D was maintained in the soil where it was ultimately degraded. As a
      consequence, emission of 1,3-D from the irrigated columns was around half of
      thatfrom the nonirrigated columns. It is concluded that surface irrigation
      represents an effective, low-cost, and readily practicable approach to lessening
      the environmental impact of 1,3-D fumigant use. In addition, the higher organic
      matter soil exhibited emissions of around one-fifth of the lower organic matter
      soil in both irrigated and nonirrigated treatments, due to markedly enhanced
      degradation of the fumigant. Organic matter amendment of soils may, therefore,
      also represent an extremely effective, relatively low-cost approach to reducing
      1,3-D emissions.

PMID- 17438769
TI  - Serum concentrations of 11 polyfluoroalkyl compounds in the u.s. population: data
      from the national health and nutrition examination survey (NHANES).
AB  - We measured the concentrations of 11 polyfluoroalkyl compounds (PFCs), including
      perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and
      perfluorohexane sulfonic acid (PFHxS) in 1562 serum samples collected from a
      representative U.S. population 12 years of age and older in the 1999-2000
      National Health and Nutrition Examination Survey. Participants represented both
      sexes, three race/ethnicities (non-Hispanic blacks, non-Hispanic whites, and
      Mexican-Americans), and four age categories (12-19 years, 20-39 years, 40-59
      years, and 60 years and older). PFCs were extracted from 100 microL of serum
      using on-line solid-phase extraction coupled to isotope dilution-high performance
      liquid chromatography-tandem mass spectrometry; limits of detection ranged from
      0.05 to 0.2 ng/ mL. PFOS, PFOA, PFHxS, and perfluorooctane sulfonamide were
      detected in all samples analyzed; 2-(N-ethyl-perfluorooctane sulfonamido) acetic
      acid, 2-(N-methyl-perfluorooctane sulfonamido) acetic acid, and perfluorononanoic
      acid were detected in more than 90% of samples, which suggests prevalent
      exposures to several PFCs in the U.S. population. The concentrations of most PFCs
      were similar regardless of the participants' ages but were higher in males than
      in females. Mexican Americans had lower concentrations than non-Hispanic blacks
      and non-Hispanic whites, whose concentrations were similar. Higher education was
      associated with higher concentrations of PFOS and PFOA. These data will serve as
      a nationally representative baseline of the U.S. population's exposure to PFCs to
      which other populations can be compared, and will play an important role in
      public health by helping set research priorities, ranging from health effects
      studies to defining sources and pathways of exposure.

PMID- 17438770
TI  - Volatilization of parathion and chlorothalonil from a potato crop simulated by
      the PEARL model.
AB  - The volatilization of pesticides from crop canopies in the field should be
      modeled within the context of evaluating environmental exposure. A model concept
      based on diffusion through a laminar air-boundary layer was incorporated into the
      PEARL model (pesticide emission assessment at regional and local scales) and used
      to simulate volatilization of the pesticides parathion and chlorothalonil from a
      potato crop in a field experiment. Rate coefficients for the competing processes
      of plant penetration, wash off, and phototransformation in the canopy had to be
      derived from a diversity of literature data. Cumulative volatilization of the
      moderately volatile parathion (31% of the dosage in 7.6 days) could be simulated
      after calibrating two input data derived for the related compound parathion
      methyl. The less volatile and more slowly transformed chlorothalonil showed 5%
      volatilization in 7.6 days, which could be explained by the simulation. Simulated
      behavior of the pesticides in the crop canopy roughly corresponded to published
      data.

PMID- 17438771
TI  - Isomers of dechlorane plus in Lake Winnipeg and Lake Ontario food webs.
AB  - The extent of bioaccumulation of the syn- and anti-isomers of Dechlorane Plus
      (DP) is assessed in archived food web samples from Lake Winnipeg and Lake
      Ontario. Concentrations of the isomers were determined using purified analytical
      solutions of individual isomers as opposed to the technical mixture. The syn
      isomer was consistently detected in all samples from both lakes; the anti-isomer
      was detected in all Lake Ontario samples, but only 45% of the samples from Lake
      Winnipeg. The pattern of bioaccumulation was different for the isomers in Lake
      Winnipeg. The anti-isomer was dominant in higher trophic level (TL) organisms
      like walleye [arithmetic mean +/- 1 x standard error: 730 +/- 120 pg/g, lipid
      weight (1w)] and goldeye (760 +/- 170 pg/g, Iw) while the syn-isomer dominated
      the lower TL organisms like zooplankton (550 +/- 40 pg/g, Iw) and mussels (430 +/
      140 pg/g, Iw). In Lake Ontario, the extent of bioaccumulation of the isomers and
      concentrations was greatest in the lower TL benthic organism, Diporeia (syn, 1307
      +/- 554; and anti, 3108 +/- 898 pg/g Iw) and also high in zooplankton (syn, 719;
      and anti, 1332 pg/g Iw). This suggests that the isomers are bioavailable in
      sediment and that, despite their molecular size, diffusion from the water column
      into zooplankton can occur. Differences in the mean fractional abundance of the
      anti-isomer (mean fanti = mean concentration of the anti-isomer divided by sum of
      mean syn- and anti-concentrations) were pronounced in sediments between lakes
      (Lake Winnipeg mean fanti = 0.610, Lake Ontario mean fanti = 0.860) and the
      extent of enrichment (anti-) and depletion (syn-) of the isomers were more marked
      in Lake Winnipeg biota. There were also differences in the biomagnification
      potentials, as measured bythe trophic magnification factor (TMF), between the
      isomers in the Lake Winnipeg food web; no statistically significant TMFs for
      either isomer were found for the

PMID- 17438772
TI  - Impact of pH on Cu accumulation kinetics in earthworm cytosol.
AB  - We studied the interaction between toxic stress and accumulation in the earthworm
      Aporrectodea caliginosa, as induced by different soil copper pools and soil
      constituents (especially pH). Earthworms were exposed in quartz sand, spiked
      soils, and field soils with different Cu concentrations and varying soil
      composition. The copper content in the earthworms was determined in the
      following: the cytosolic fraction, a granular fraction and a fraction consisting
      of tissue fragments, cell membranes and intact cells. The highest amount of Cu
      was found in the cytosolic fraction. The other fractions varied only slightly in
      response to changes in any of the copper pools in soil. Cytosolic copper was the
      best predictor of Cu availability to earthworms collected from soils at constant
      pH, as statistically significant correlations were obtained with pore water pCu
      at constant pH in earthworms exposed in quartz sand. This correlation was lost
      for cytosolic Cu concentrations in earthworms exposed to spiked soils and field
      soils at differing pHs. Instead, cytosolic copper correlated well to Cu in either
      pore water or solid phase. Soil pH not only plays an important role in the
      availability of metals and therefore on their uptake fluxes, but internal
      competition of Cu2+ and H+ at physiologically active binding sites also explained
      these apparent contradictions and increased the predictability of body burdens
      significantly.

PMID- 17438773
TI  - Comparative analysis of three tetrachloroethene to ethene halorespiring consortia
      suggests functional redundancy.
AB  - Three anaerobic, dechlorinating consortia were enriched from different sites
      using methanol and tetrachloroethene (PCE) and maintained for approximately 3
      years. These consortia were evaluated using chemical species analysis including
      distribution of dechlorination products, production of organic acids and methane,
      and using qualitative and quantitative PCR (qPCR), terminal restriction fragment
      length polymorphism (TRFLP), and denaturing gradient gel electrophoresis (DGGE)
      with primers specific to Dehalococcoides 16S rRNA gene sequences. TRFLP and
      analysis of organic acids revealed differing fermentative populations in each
      consortium, which were dominated by acetogens. Monitoring methane production
      combined with qPCR for archaea showed that complete dechlorination of PCE-to
      ethene occurred in the presence and absence of methanogens. The 16S rRNA gene
      based analyses demonstrated that enrichment with PCE resulted in dechlorinating
      communities dominated by Dehalococcoides and Dehalobacter, and that up to four
      different PCE-dechlorinating organisms coexisted in one consortium. Further, the
      DGGE analysis suggested that at least one consortium contained multiple
      Dehalococcoides strains. The combined analysis of 16S rRNA and reductive
      dehalogenase genes suggested that one consortium contained a member of the
      Dehalococcoides "Cornell" group with the ability to respire VC.

PMID- 17438774
TI  - Importance of dissolved neutral mercury sulfides for methyl mercury production in
      contaminated sediments.
AB  - Biotic transformation of inorganic mercury, Hg(II), to mono methyl mercury (MeHg)
      is proposed to be largely controlled by passive uptake of neutral Hg complexes by
      sulfate reducing bacteria (SRB). In this study, the chemical speciation of Hg(II)
      in seven locally contaminated sediments covering environments such as (i)
      brackish water, (ii) low-productivity freshwater, and, (iii) high-productivity
      freshwater was related to potential Hg methylation rates, determined by
      incubation at 23 degrees C for 48 h under N2(g), and to total MeHg concentrations
      in sediments. Pore water speciation was modeled considering Hg complexes with
      halides, organic thiols [Hg(SR)2(aq), associated to dissolved organic matter],
      monosulfides, and bisulfides. The sum of neutral mercury sulfides [Hg(SH)20(aq)]
      and [HgS0(aq)] was significantly, positively (p < 0.001, n = 20) correlated to
      the specific methylation rate constant (Km, day(-1)) at depths of 5-100 cm in two
      brackish water sediments. Total Hg, total mercury sulfides or Hg(SR)2(aq) in pore
      water gave no significant relationships with Km. In two subsets of freshwater
      sediments, neutral mercury sulfides were positively correlated to total Hg in
      pore water, and therefore, total Hg also gave significant relationships with Km.
      The sum of [Hg(SH)20(aq)] and [HgS0(aq)] was significantly, positively correlated
      to total sediment MeHg (microg kg-1) in brackish waters (p < 0.001, n = 23), in
      southern, high-productivity freshwaters (p < 0.001, n = 20), as well as in
      northern, low-productivity freshwater (p = 0.048, n = 6). The slopes (b, b') of
      the relationships Km (day-1) = a + b([Hg(SH)20(aq)] + [HgS0(aq)]) and MeHg
      (microg kg-1) = a' + b'([Hg(SH)20(aq)] + [HgS0(aq)]) showed an inverse
      relationship with the C/N ratio, supposedly reflecting differences in primary
      production and energy-rich organic matter availability among sites. We conclude
      that concentrations of neutral inorganic mercury sulfide species, together with
      the availability of energy-rich organic matter, largely control Hg methylation
      rates in contaminated sediments. Furthermore, Hg(SH)20(aq) is suggested to be the
      dominant species taken up by MeHg producing bacteria in organic-rich sediments
      without formation of HgS(s).

PMID- 17438775
TI  - The copper-mobilizing-potential of dissolved organic matter in soils varies 10
      fold depending on soil incubation and extraction procedures.
AB  - Copper is mobilized in soil by dissolved organic matter (DOM) but the role of DOM
      quality in this process is unclear. A one-step resin-exchange method was
      developed to measure the Cu-Mobilizing-Potential (CuMP) of DOM at pCu 11.3 and pH
      7.0, representing background values. The CuMP of DOM was measured in soil
      solutions of 13 uncontaminated soils with different DOM extraction methods. The
      CuMP, expressed per unit dissolved organic carbon (DOC), varied 10-fold and
      followed the order water extracts > 0.01 M CaCl2 extracts > pore water. Soil
      solutions, obtained from soils that were stored air-dry for a long time or were
      subjected to drying-wetting cycles, had elevated DOC concentration, but the DOM
      had a low CuMP. Prolonged soil incubations decreased the DOC concentration and
      increased the CuMP, suggesting that most of the initially elevated DOM is less
      humified and has lower Cu affinity than DOM remaining after incubation. A
      significant positive correlation between the specific UV-absorption of DOM
      (indicating aromaticity) and CuMP was found for all DOM samples (R(2) = 0.58). It
      is concluded that the DOC concentration in soil is an insufficient predictor for
      the Cu mobilization and that DOM samples isolated from air-dried soils are
      distinct from those of soils kept moist.

PMID- 17438776
TI  - Role of sediment resuspension in the remobilization of particulate-phase metals
      from coastal sediments.
AB  - The release of particulate-phase trace metals due to sediment resuspension has
      been investigated by combining erosion chamber experiments that apply a range of
      shear stresses typically encountered in coastal environments with a shear stress
      record simulated by a hydrodynamic model. Two sites with contrasting sediment
      chemistry were investigated. Sediment particles enriched in silver, copper, and
      lead, 4-50 times greater than the bulk surface-sediment content, were the first
      particles to be eroded. As the shear-stress level was increased in the chamber,
      the total mass eroded increased, butthe enrichment of these trace metals fell,
      approaching the bulk-sediment content. From the temporal distribution of shear
      stress generated by the hydrodynamic model for a site in Boston Harbor,
      resuspension fluxes were estimated. The erosion threshold of this site is
      exceeded during spring tides, releasing the particles enriched in trace metals
      into the water column. Due to the higher trace metal content and the regularity
      of resuspension, low-energy resuspension events (up to a shear stress of 0.2
      N/m(2)) contribute up to 60% of the resuspension metal flux in an average year.
      The estimated annual quantity of copper and lead resuspended into the water
      column is higher than estimates of the total riverine flux for these metals.
      These results indicate that sediment resuspension is a very important mechanism
      for releasing metals into the water column and provide new insight into the
      chemical and physical processes controlling the long-term fate of trace metals in
      contaminated sediments.

PMID- 17438777
TI  - Efflorescence transitions of ammonium sulfate particles coated with secondary
      organic aerosol.
AB  - Ammonium sulfate particles were generated by atomization and introduced into a
      smog chamber where they were coated with secondary organic aerosol from
      ozonolysis of limonene or alpha-pinene. These mixed particles were then sampled
      with a humidified Tandem-DMA system where a monodisperse aerosol population was
      selected, humidified, and dried to observe the relative humidity (RH) at which
      the particles returned to the original dry diameter. The volume fraction of
      secondary organic aerosol (SOA) in the mixed particles ranged from 0.59 to 0.94
      for limonene SOA and 0.54 to 0.72 for alpha-pinene SOA. Efflorescence RHs for our
      mixed aerosols were in the range of 28-34%, similar to our observation of 32% ERH
      for pure ammonium sulfate nanoparticles. These findings indicate that the effect
      of SOA on the ERH of inorganic salts in the atmosphere may be negligible.

PMID- 17438778
TI  - Wavelength dependence of the photochemical reduction of iron in arctic seawater.
AB  - Chemiluminescence measurements of the photochemical reduction of iron in cold,
      high-latitude waters (79 degrees N) show that a significant fraction (20%) of the
      dissolved iron is reduced when exposed to sunlight. The reduction is immediately
      initiated and the transition to a steady-state concentration of approximately 200
      pM photochemical Fe(II) is achieved within approximately 40 s. The photochemical
      Fe(ll) is reoxidized to Fe(III) in less than a minute upon blocking the sunlight,
      much faster than expected, which is ascribed to reaction with photochemically
      produced oxidants. Using filters to block different ranges of the incident
      sunlight it was found that 35% of the photochemical Fe(II) was produced in the UV
      B range (300-315 nm), 30% in the range 315-360 nm, and 30% at higher wavelengths.
      Measurements of light attenuation as a function of depth indicate that
      photochemical Fe(II) at a depth of 5 m in high-latitude waters should amount to
      approximately10% of that at the surface. The fast kinetics modulate the paramount
      importance that photochemical reactions may have on the bioavailability of iron
      in surface waters.

PMID- 17438779
TI  - Growth and yields of dechlorinators, acetogens, and methanogens during reductive
      dechlorination of chlorinated ethenes and dihaloelimination of 1 ,2
      dichloroethane.
AB  - The population dynamics of a mixed microbial culture dechlorinating
      trichloroethene (TCE), cis-1,2-dichloroethene (cDCE), 1,2-dichloroethane (1,2
      DCA), and vinyl chloride (VC) to ethene were studied. Quantitative PCR revealed
      that Dehalococcoides, Geobacter, Sporomusa, Spirochaetes, and Methanomicrobiales
      phylotypes grew in short-term experiments. Both Geobacter and Dehalococcoides
      populations grew during TCE dechlorination to cDCE, but only Dehalococcoides
      populations grew during further dechlorination to ethene. The cell yields for
      Dehalococcoides determined in this study were similar on an electron equivalent
      basis regardless of the chlorinated compound transformed: (0.9+/-0.3) x 10(8)16S
      rRNA gene copies/microelectron equivalent (microeeq) ethene produced during cDCE
      dechlorination, (1.5 +/-0.3) x 10(8) copies/microeeq ethene produced during VC
      dechlorination, and (1.6+/-0.8) x 10(8) copies/ u,eeq ethene produced during 1,2
      DCA dihaloelimination. The yield for the Geobacter population on TCE was
      estimated to be (1+/-0.5) x 10(8) copies/microeeq cDCE produced. Calculations
      showed that the Geobacter population was likely responsible for approximately 80%
      of the TCE dechlorinated to cDCE in this experiment. Acetogenesis by a Sporomusa
      population was the main competition to dechlorination for reducing equivalents.
      Sporomusa did not transform any chlorinated substrates tested, but was capable of
      converting methanol to acetate and hydrogen for dechlorination. Understanding the
      functions of various populations in mixed communities may explain why
      Dehalococcoides spp. are active at some sites and not others, and may also assist
      in optimizing the growth of bioaugmentation cultures, both in the laboratory and
      in the field.

PMID- 17438780
TI  - Hydrogen thresholds and steady-state concentrations associated with microbial
      arsenate respiration.
AB  - H2 thresholds for microbial respiration of arsenate (As(V)) were investigated in
      a pure culture of Sulfurospirillum arsenophilum. H2 was consumed to threshold
      concentrations of 0.03-0.09 nmol/L with As(V) as terminal electron acceptor,
      allowing for a Gibbs free-energy yield of 36-41 kJ per mol of reaction. These
      thresholds are among the lowest measured for anaerobic respirers and fall into
      the range of denitrifiers or Fe(III)-reducers. In sediments from an arsenic
      contaminated aquifer in the Red River flood plain, Vietnam, H2 levels decreased
      to 0.4-2 nmol/L when As(V) was added under anoxic conditions. When As-(V) was
      depleted, H2 concentrations rebounded by a factor of 10, a level similar to that
      observed in arsenic-free controls. The sediment-associated microbial population
      completely reduced millimolar levels of As(V) to arsenite (As-(III)) within a few
      days. The rate of As(V)-reduction was essentially the same in sediments amended
      with a pure culture of S. arsenophilum. These findings together with a review of
      observed H2 threshold and steady-state values suggest that microbial As(V)
      respirers have a competitive advantage over several other anaerobic respirers
      through their ability to thrive at low H2 levels.

PMID- 17438781
TI  - Growth of Dehalococcoides strains with chlorophenols as electron acceptors.
AB  - Dehalococcoides strains reductively dechlorinate a wide variety of halogenated
      compounds including chlorinated benzenes, biphenyls, naphthalenes, dioxins, and
      ethenes. Recent genome sequencing of the two Dehalococcoides strains CBDB1 and
      195 revealed the presence of 32 and 18 reductive dehalogenase homologous genes,
      respectively, and therefore suggested an even higher dechlorinating potential
      than previously anticipated. Here, we demonstrate reductive dehalogenation of
      chlorophenol congeners by Dehalococcoides strains CBDB1 and 195. Strain CBDB1
      completely converted 2,3-dichlorophenol, all six trichlorophenols, all three
      tetrachlorophenols, and pentachlorophenol to lower chlorinated phenols. Observed
      dechlorination rates in batch cultures with cell numbers of 10(7) mL(-1) amounted
      up to 35 microM day(-1). Chlorophenols were preferentially dechlorinated in the
      ortho position, but also doubly flanked and singly flanked meta- or para-chlorine
      substituents were removed. We used a newly designed computer-assisted direct cell
      counting protocol and quantitative PCR to demonstrate that strain CBDB1 uses
      chlorophenols as electron acceptors for respiratory growth. The growth yield of
      strain CBDB1 with 2,3-dichlorophenol was 7.6 x 10(13) cells per mol of Cl-
      released, and the growth rate was 0.41 day(-1). For strain 195, fast ortho
      dechlorination of 2,3-dichlorophenol, 2,3,4-trichlorophenol, and 2,3,6
      trichlorophenol was detected, with only the ortho chlorine removed. Because
      chlorinated phenolic compounds are widely distributed as natural components in
      anaerobic environments, our results reveal one mode in which the Dehalococcoides
      species could have survived through earth history.

PMID- 17438782
TI  - Adsorption of pathogenic prion protein to quartz sand.
AB  - Management responses to prion diseases of cattle, deer, and elk create a
      significant need for safe and effective disposal of infected carcasses and other
      materials. Furthermore, soil may contribute to the horizontal transmission of
      sheep scrapie and cervid chronic wasting disease by serving as an environmental
      reservoirforthe infectious agent. As an initial step toward understanding prion
      mobility in porous materials such as soil and landfilled waste, the influence of
      pH and ionic strength (l) on pathogenic prion protein (PrPsc) properties (viz.
      aggregation state and zeta-potential) and adsorption to quartz sand was
      investigated. The apparent average isoelectric point of PrPsc aggregates was 4.6.
      PrPsc aggregate size was largest between pH 4 and 6, and increased with
      increasing l at pH 7. Adsorption to quartz sand was maximal near the apparent
      isoelectric point of PrPsc aggregates and decreased as pH either declined or
      increased. PrPsc adsorption increased as suspension l increased, and reached an
      apparent plateau at l approximately 0.1 M. While trends with pH and l in PrPsc
      attachment to quartz surfaces were consistent with predictions based on Born-DLVO
      theory, non-DLVO forces appeared to contribute to adsorption at pH 7 and 9 (l =
      10 mM). Our findings suggest that disposal strategies that elevate pH (e.g.,
      burial in lime or fly ash), may increase PrPsc mobility. Similarly, PrPsc
      mobility may increase as a landfill ages, due to increases in pH and decreases in
      l of the leachate.

PMID- 17438783
TI  - Watershed processing of atmospheric polychlorinated biphenyl inputs.
AB  - Indirect atmospheric deposition of PCBs was examined in subwatersheds of the
      Delaware River Estuary. Tributary PCB loads and atmospheric PCB concentrations
      were used to understand the pass-through efficiencies for nine rivers/ creeks for
      which PCB inputs appeared to be dominated by atmospheric deposition. The pass
      through efficiency, E, was calculated from tributary loads and atmospheric
      deposition fluxes. Unfortunately, uncertainties in the gaseous and dry particle
      deposition velocities, vg and vd, respectively, render the calculated atmospheric
      deposition fluxes highly uncertain. In order to circumvent this problem, export
      of PCBs from the watershed was related directly to atmospheric PCB concentrations
      via a new mass transfer coefficient, the watershed delivery rate or vws, which
      describes the process by which the watershed transfers PCBs from the airto the
      River's main stem. vws increases with increasing chlorination and is
      significantly correlated with vapor pressure. This trend suggests that the
      transfer of PCBs from the atmosphere to the River via the watershed is more
      efficient for high molecular weight PCBs than for low molecular weight PCBs. This
      may indicate that the selected watersheds are at or close to equilibrium with
      respect to gaseous exchange of PCBs, such that lower molecular weight congeners
      undergo substantial revolatilization after deposition. The magnitude of the pass
      through efficiency, E, depends on the deposition velocities used to calculate the
      atmospheric deposition flux, but when congener-specific deposition velocities are
      used, E is independent of vapor pressure and is relatively constant at about 3%.

PMID- 17438784
TI  - Stability of metal-glutathione complexes during oxidation by hydrogen peroxide
      and Cu(II)-catalysis.
AB  - Thiol-containing ligands such as glutathione (GSH) are expected to degrade in the
      presence of oxygen; however, complexation by Hg, Ag, and other trace metals may
      protect free thiol functional groups (R-S-) from oxidation, leading to
      persistence in surface water environments. In this study, the stability of GSH
      complexes with Hg2+, Ag+, and other metals including Cd2+, Zn2+, and Pb2+ was
      assessed during exposure to two potential environmental oxidants: H202 and Cu2+.
      The results indicated that Hg-(GSH)2 and Ag(GSH) complexes were completely stable
      for at least 2 days in the presence of either H202 or Cu2+. In contrast, free GSH
      oxidized within minutes to hours. Complexation by Cd, Zn, and Pb slightly
      decreased or did not significantly affect the oxidation rate of GSH, depending
      upon the pH (tested between pH 6 and 9). Thermodynamic modeling of GSH speciation
      demonstrated that the observed oxidation rates were not consistent with predicted
      free GSH3- concentration. These results indicated that Cd-, Zn-, and Pb-GSH
      complexes were susceptible to oxidation by a mechanism that differs from GSH3-
      oxidation. In contrast, Hg- and Ag-GSH complexes were inert for days, suggesting
      that they are stable for relatively long periods in the oxic water column. These
      results demonstrate that coordination of Hg(II) and Ag(I) to thiol-containing
      ligands can potentially increase persistence and transport in surface waters.

PMID- 17438785
TI  - Monod kinetics for aerobic biodegradation of petroleum hydrocarbons in
      unsaturated soil microcosms.
AB  - We use Monod kinetics to calibrate previously published data that documentthe
      aerobic biodegradation of hydrocarbon vapors in soil microcosms from a weathered
      petroleum spill site. Monod kinetics offer insight into biodegradation mechanics
      because they address biomass growth as well as substrate depletion. A blend of
      five aromatics and five alkanes dose the microcosm sets at four strengths, and a
      finite difference model describes the response superimposed across the
      constituent substrates. An observed initial biomass X0 of 125 g biomass/m(3) soil
      moisture and an endogendous decay rate b of 0.102 day(-1) calibrate all four
      dosages and agree with heterotrophic plate counts. Common maximum specific growth
      rates microMJ and half saturation constants KSJ calibrate each constituent across
      the four dosages. The biodegradable alkanes exhibit microMJ values ranging from
      0.0190 to 0.0996 day(-1), while the aromatic rates vary from 0.0946 to 0.322 day(
      1). One of the alkanes (2,2,4-trimethylpentane) is recalcitrant. The half
      saturation constants range from 0.000083 to 0.000355 g substrate/m(3) soil
      moisture for the biodegradable alkanes, which imply zero-order kinetics. The
      aromatic KSJ values vary from 5.02 to 14.3 g substrate/m(3) soil moisture, and
      suggest first-order kinetics. The yield YJ increases with dosage concentration
      for all the biodegradable constituents, varying from 0.0533 to 1.58 g biomass/g
      substrate.

PMID- 17438786
TI  - Metabolism of BTEX and naphtha compounds to methane in oil sands tailings.
AB  - Naphtha, comprising low molecular weight aliphatics and aromatics (C3-C14), is
      used as a diluent in processing of bitumen from oil sands. A small fraction (<1%)
      is lost to tailings waste and incorporated into mature fine tailings (MFT). BTEX
      (benzene, toluene, ethylbenzene, and xylenes) and whole naphtha were assessed for
      biodegradation under methanogenic conditions using MFT from an oil sands tailings
      settling basin. MFT spiked with 0.05-0.1% w/v of BTEX compounds produced up to
      2.1 (+/-0.1) mmol of methane during 36 weeks of incubation. Metabolism of 0.5
      1.0% w/v naphtha in MFT yielded up to 5.7 (+/-0.2) mmol of methane during 46
      weeks of incubation. Gas chromatographic analyses showed that BTEX degraded in
      the sequence: toluene > o-xylene > m- plus p-xylene > ethylbenzene > benzene.
      Only 15-23% of whole naphtha, mainly n-alkanes (in the sequence: nonane > octane
      > heptane) and some BTEX compounds (toluene > o-xylene > m-xylene), was
      metabolized. Other naphtha constituents, such as iso-paraffins and naphthenes,
      remained unchanged during this period. These results suggest that the microbial
      communities in the MFT can readily utilize certain fractions of unrecovered
      naphtha in oil sands tailings and support methanogenesis in settling basins.
      Current study findings could influence extraction process, MFT management, and
      reclamation options.

PMID- 17438787
TI  - Controlled OH radical production via ozone-alkene reactions for use in aerosol
      aging studies.
AB  - We present a novel method for continuous, stable OH radical production for use in
      smog chamber studies, especially those focused on organic aerosol aging. Our
      source produces OH radicals from the reaction of 2,3-dimethyl-2-butene and ozone
      and is unique as a method that requires neither NOx nor UV photolysis of a
      radical precursor. Typical radical concentrations are in the range of (4-8) x
      10(6) molec cm(-3) and are easily sustainable over experimental time scales of
      several hours. We discuss design considerations, radical production capability
      under different operating conditions, and the core source chemistry. As a proof
      of concept we present preliminary results from oxidation of n-hexacosane aerosol
      observed with an Aerodyne Aerosol Mass Spectrometer. The extent of hexacosane
      oxidation is sufficient to significantly change the organic aerosol mass spectrum
      by virtue of fast heterogeneous uptake of OH radicals at the particle surface,
      with a calculated uptake coefficient gamma = 1.04 +/-0.21.

PMID- 17438788
TI  - Source-dependent variation in hydroxyl radical production by airborne particulate
      matter.
AB  - Epidemiological studies suggest exposure to airborne particles is responsible for
      a wide range of adverse health effects, potentially arising from particle-induced
      oxidative stress. A highly sensitive fluorescence method was employed to measure
      the production of hydroxyl radical by a broad range of particle types including
      urban dust, diesel particulate matter, coal fly ash, kaolinite, and silica.
      Little or no production of *OH was observed in the absence of an added electron
      donor or H202. In the presence of a biological electron donor (NADPH, 3 mM), the
      rate of *OH production (ROH) for 3 mg/mL of these particles varied from 23 nM s(
      1) for diesel particulate matter (SRM 2975) to 0.20 nM s(-1) for coal fly ash
      (SRM 2689). No detectable *OH was produced by kaolinite or silica. Hydroxyl
      radical formation was eliminated under anaerobic conditions and in the presence
      of catalase, indicating that 02 and H202 are required for its generation. Partial
      inhibition of *OH formation by superoxide dismutase (SOD) was also observed in
      some cases, suggesting that superoxide (O2*-) is also involved. The metal
      chelator deferoxamine mesylate (DFX) in most cases suppressed *OH formation, but
      diethylenetriaminepentaacetic acid (DTPA) generally enhanced it, implicating
      metal ion reactions in OH generation as well. The dependence of ROH on NADPH
      concentration further implicates particle surface reactions in *OH formation. To
      our knowledge, these measurements provide the first quantitative estimate of ROH
      for a broad range of particle types.

PMID- 17438789
TI  - Accumulation, whole-body depletion, and debromination of decabromodiphenyl ether
      in male sprague-dawley rats following dietary exposure.
AB  - Decabromodiphenyl ether (BDE-209) isthe major component in the flame-retardant
      formulation DecaBDE which is incorporated into numerous consumer goods ranging
      from upholsteries to electronics. Because of the high volume of DecaBDE produced,
      its presence in consumer products and the environment, and the finding of BDE-209
      in the blood of exposed workers, the extent of bioavailability, persistence, and
      potential debromination are important issues. To measure the bioconcentration,
      distribution, reductive debromination, and whole-body half-lives of BDE-209 after
      multiple low doses in an animal model, we dosed rats with a commercial DecaBDE
      (0.3 microg/g of diet) for 21 days and measured tissue polybrominated diphenyl
      ether levels during a 21 day withdrawal period. BDE-209, three nona-BDEs, and
      four octa-BDEs accumulated in the rats and distributed proportionately throughout
      the body. Only 5% of the total BDE-209 dose was present as parent compound in the
      rats after 21 days of dosing and <4% in the feces, suggesting extensive
      metabolism. A nona-BDE (BDE-207) and two octa-BDEs (BDEs-201 and -197) appeared
      to form via meta-debromination(s) of BDE-209 to a minimal extent (1% of the total
      BDE-209 dose). The wholebody half-lives tended to increase with decreasing
      bromination; however, two octa-BDEs, presumably forming from debromination,
      increased in the rats after 21 days of withdrawal and demonstrated the potential
      for BDE-209 to form more persistent lipophilic compounds in vivo.

PMID- 17438790
TI  - Did smoke from the Kuwait oil well fires affect Iranian archaeological heritage?
AB  - The combustion of crude oil produces a wide range of pollutants, including gases,
      volatile organic compounds, polycyclic aromatic hydrocarbons, acid compounds
      (e.g., sulfuric acid), and soot. Several of these pollutants have been linked
      with the deterioration and blackening of monuments. The paper reports the results
      of an investigation on the causes of the soiling of cultural remains at important
      archaeological sites in the provinces of Khuzestan and Fars, in southern Iran,
      assumed to be an effect of the Persian Gulf oil well fires of 1991. Different
      analytical techniques were applied to characterize the mineralogical composition
      of the damage layers, investigate the deposition of atmospheric particles,
      measure the anion concentrations, and identify and quantify the carbon
      components. The results showed that the black deposits on the surfaces of the
      Iranian monuments considered are mainly microbiotic crusts produced by
      cyanobacterial growth. No evidence was found of the deposition of particulate
      matter (smoke) produced by the Kuwait oil fires during the Gulf War.

PMID- 17438791
TI  - Formation of chloroform and other chlorinated byproducts by chlorination of
      triclosan-containing antibacterial products.
AB  - Triclosan is a widely used antibacterial agent found in many personal hygiene
      products. Although it has previously been established that pure triclosan and
      free chlorine readily react, interactions between triclosan-containing consumer
      products and free chlorine have not previously been analyzed in great depth.
      Sixteen double-blinded solutions including both triclosan-containing (1.14-3.12
      mg triclosan/g product) and triclosan-free products were contacted with free
      chlorine at pH 7. Products detected included (chlorophenoxy) phenols, 2,4
      dichlorophenol, 2,4,6-trichlorophenol, and chloroform. The daughter product
      yields were found to be highly variable and were dependent on the antimicrobial
      product investigated, the free chlorine to triclosan ratio, and the temperature
      at which the study was conducted. Lowering the temperature from 40 to 30 degrees
      C resulted in a decreased average chloroform yield from 0.50 to 0.37 mol
      chloroform/mol triclosan consumed after 1 min of reaction time for an initial
      free chlorine concentration of 4.0 mg/L as Cl2. At 40 degrees C the average molar
      chloroform yields decreased to 0.29 and <0.1 when the initial free chlorine
      concentration was decreased to either 2.0 or 1.0 mg/L as Cl2, respectively. Field
      experiments, in which Atlanta, GA and Danville, VA tap waters were augmented with
      various soap products, exhibited results varying from the laboratory experiments
      in that different productyields were observed. These differences are attributed
      to the chlorine demand of constituents in the tap water. A simple exposure model
      suggests that exposure to chloroform can be significant under some conditions.

PMID- 17438792
TI  - Equilibrium distribution of polysulfide ions in aqueous solutions at different
      temperatures by rapid single phase derivatization.
AB  - Polysulfides are abundant form of reduced sulfur compounds whose distribution in
      aquatic systems continues to pose environmental challenge. The Gibbs free-energy
      of formation, enthalpy of formation, and standard entropy of inorganic
      polysulfides were derived based on measurements of the temperature-dependent
      distribution of inorganic polysulfides in supersaturated aqueous polysulfide
      solutions. The data complements the relevant Gibbs free-energy data that were
      derived in our recent publication. The thermodynamic data show that the average
      polysulfide length is increased and polysulfides dissolve better at elevated
      temperatures, though the extent of this increase is pH dependent. At high pH (pH
      > 10) increasing the temperature from 25 to 80 degrees C results in a 5.6%
      increase in the concentration of polysulfide bound sulfur (i.e., dissolved
      zerovalent sulfur) and increases the average chain length (n) by 0.2 sulfur
      atoms, whereas at pH 8.2 the n increases by 0.25, and the dissolved polysulfide
      sulfur increases threefold.

PMID- 17438793
TI  - Microbial and chemical assessment of regions within New Orleans, LA impacted by
      Hurricane Katrina.
AB  - The city of New Orleans, LA was severely impacted by flooding and wind damage
      following landfall of Hurricane Katrina in August 2005. The city's drinking water
      infrastructure was severely compromised and massive amounts of sediment were
      redeposited throughout the flooded region. Thousands of homes were water-damaged
      resulting in the rapid growth of mold. In September and October 2005 a
      convenience sample of selected homes, tap water, surface water, and sediment
      within New Orleans was assessed for mold contamination, microbial contamination,
      and heavy metal concentrations. At selected sites, indoor mold spore
      concentrations were compared to outdoor concentrations. The purpose of this study
      was to conduct a baseline environmental assessment in an effort to identify
      public health threats caused by wind and flood damage. Surface waters contained
      high concentrations of bacterial indicators whereas no bacteria were detected in
      tap water, even from taps containing no chlorine residual. Sediment samples
      contained concentrations of lead and arsenic similarto pre-Katrina
      concentrations. Outdoor total spore (sp) concentrations ranged from >6500 to 84
      713 sp/m(3). Indoor concentrations ranged from 6142 to 735 123 sp/m(3). For the
      13 locations with matched indoor/ outdoor samples, the mean indoor/outdoor spore
      ratio was 4.11 (ranging from 0.27 to >11.44). Inside 5 of the 13 homes, total
      spore counts/m(3) exceeded 100 000, with measurements in the moldiest home
      exceeding 700 000 sp/ m(3). In conclusion, surface waters had high concentrations
      of bacterial contamination but no bacterial indicators were present in tap water.
      Sediment samples did not have appreciable increases in lead or arsenic. Flooded
      homes, however, contained substantial concentrations of mold which could present
      a public health exposure route to individuals repopulating and restoring the City
      of New Orleans.

PMID- 17438794
TI  - Chemical indices and methods of multivariate statistics as a tool for odor
      classification.
AB  - Industrial and agricultural off-gas streams are comprised of numerous volatile
      compounds, many of which have substantially different odorous properties. State
      of-the-art waste-gas treatment includes the characterization of these molecules
      and is directed at, if possible, either the avoidance of such odorants during
      processing or the use of existing standardized air purification techniques like
      bioscrubbing or afterburning, which however, often show low efficiency under
      ecological and economical regards. Selective odor separation from the off-gas
      streams could ease many of these disadvantages but is not yet widely applicable.
      Thus, the aim of this paper is to identify possible model substances in selective
      odor separation research from 155 volatile molecules mainly originating from
      livestock facilities, fat refineries, and cocoa and coffee production by
      knowledge-based methods. All compounds are examined with regard to their
      structure and information-content using topological and information-theoretical
      indices. Resulting data are fitted in an observation matrix, and similarities
      between the substances are computed. Principal component analysis and k-means
      cluster analysis are conducted showing that clustering of indices data can depict
      odor information correlating well to molecular composition and molecular shape.
      Quantitative molecule describtion along with the application of such statistical
      means therefore provide a good classification tool of malodorant structure
      properties with no thermodynamic data needed. The approximate look-alike shape of
      odorous compounds within the clusters suggests a fair choice of possible model
      molecules.

PMID- 17438795
TI  - Application of land use regression to estimate long-term concentrations of
      traffic-related nitrogen oxides and fine particulate matter.
AB  - Land use regression (LUR) is a promising technique for predicting ambient air
      pollutant concentrations at high spatial resolution. We expand on previous work
      by modeling oxides of nitrogen and fine particulate matter in Vancouver, Canada,
      using two measures of traffic. Systematic review of historical data identified
      optimal sampling periods for NO and N02. Integrated 14-day mean concentrations
      were measured with passive samplers at 116 sites in the spring and fall of 2003.
      Study estimates for annual mean NO and NO2 ranged from 5.4-98.7 and 4.8-28.0 ppb,
      respectively. Regulatory measurements ranged from 4.8-29.7 and 9.0-24.1 ppb and
      exhibited less spatial variability. Measurements of particle mass concentration
      (PM2.5) and light absorbance (ABS) were made at a subset of 25 sites during
      another campaign. Fifty-five variables describing each sampling site were
      generated in a Geographic Information System (GIS) and linear regression models
      for NO, NO2, PM2.5, and ABS were built with the most predictive covariates.
      Adjusted R(2) values ranged from 0.39 to 0.62 and were similar across traffic
      metrics. Resulting maps show the distribution of NO to be more heterogeneous than
      that of NO2, supporting the usefulness of this approach for assessing spatial
      patterns of traffic-related pollution.

PMID- 17438796
TI  - A spatial model of urban winter woodsmoke concentrations.
AB  - In many urban areas, residential wood burning is a significant wintertime source
      of PM2.5. In this study, we used a combination of fixed and mobile monitoring
      along with a novel spatial buffering procedure to estimate the spatial patterns
      of woodsmoke. Two-week average PM2.5 and levoglucosan (a marker for wood smoke)
      concentrations were concurrently measured at upto seven sites in the study
      region. In addition, pre-selected routes spanning the major population areas in
      and around Vancouver, B.C. were traversed during 19 cold, clear winter evenings
      from November, 2004 to March, 2005 by a vehicle equipped with GPS receiver and a
      nephelometer. Fifteen-second-average values of light scattering coefficient (bsp)
      were adjusted for variations between evenings and then combined into a single,
      highly resolved map of nighttime winter bsp levels. A relatively simple but
      robust (R(2) = 0.64) land use regression model was developed using selected
      spatial covariates to predict these temporally adjusted bsp values. The bsp
      values predicted by this model were also correlated with the measured average
      levoglucosan concentrations at our fixed site locations (R(2) = 0.66). This
      model, the first application of land use regression for woodsmoke, enabled the
      identification and prediction of previously unrecognized high woodsmoke regions
      within an urban airshed.

PMID- 17438797
TI  - Kinetic analysis of microbial reduction of Fe(III) in nontronite.
AB  - Microbial reduction of structural Fe(III) in nontronite (NAu-2) was studied in
      batch cultures under non-growth condition using Shewanella putrefaciens strain
      CN32. The rate and extent of structural Fe(III) reduction was examined as a
      function of electron acceptor [Fe(III)] and bacterial concentration. Fe(ll)
      sorption onto NAu-2 and CN32 surfaces was independently measured and described by
      the Langmuir expression with the affinity constant (log K) of 3.21 and 3.30 for
      NAu-2 and bacteria, respectively. The Fe(II) sorption capacity of NAu-2 decreased
      with increasing NAu-2 concentration, suggesting a particle aggregation effect. An
      empirical equation for maximum sorption capacity was derived from the sorption
      isotherms as a function of NAu-2 concentration. The total reactive surface
      concentration of Fe(III) was proposed as a proxy for the "effective" or
      bioaccessible Fe(III) concentration. The initial rate of microbial reduction was
      first-order with respect to the effective Fe-(III) concentration. A kinetic
      biogeochemical model was assembled that incorporated the first-order rate
      expression with respect to the effective Fe(III) concentration, Fe(II) sorption
      to cell and NAu-2 surfaces, and the empirical equation for maximum sorption
      capacity. The model successfully described the experimental results with variable
      NAu-2 concentration. The initial rate of microbial reduction of Fe(III) in NAu-2
      increased with increasing cell concentration from 10(2) up to approximately 10(8)
      cells/mL, and then leveled off with further increase. A saturation-type kinetics
      with respect to cell concentration was required to describe microbial reduction
      of Fe(III) in NAu-2 as a function of cell concentration. Overall, our results
      indicated that the kinetics of microbial reduction of Fe(III) in NAu-2 can be
      modeled at variable concentration of key variables (clay and cell concentration)
      by considering the surface saturation, Fe(II) production, and its sorption to NAu
      2 and cell surfaces.

PMID- 17438798
TI  - Indicators for the exposure assessment of transformation products of organic
      micropollutants.
AB  - Environmental transformation products of organic micropollutants have the
      potential to be similarly or even more mobile, persistent, ortoxic than their
      parent compounds. They should, therefore, be included in chemical hazard and risk
      assessment procedures as well as in the assessment of soil and water quality. To
      fulfill this requirement most efficiently, screening approaches that select
      relevant transformation products for detailed assessment are needed. This paper
      presents two process-based multimedia, multispecies models that allow us to
      quantitatively estimate the environmental fate of transformation products. The
      resulting exposure patterns are assessed with two indicators: joint persistence
      (JP), which describes the temporal extent of environmental exposure to a parent
      compound and its transformation products, and the predicted relative aquatic
      concentrations (RAC), which estimate the relative concentrations of parent
      compounds and their transformation products in surface water bodies. As a case
      study, JP and RAC are calculated for 16 pesticides and their relevant
      transformation products. The results for the JP indicator confirm the importance
      of considering transformation products in the assessment of overall persistence;
      for example, in the context of PBT assessments. Comparison of RAC results with
      monitoring data on herbicides and their transformation products shows the
      suitability of our approach for estimating relative concentrations in surface
      water, and as a consequence, its usefulness in identifying transformation
      products for future water quality monitoring programs. Transformation products of
      triketones and other highly used acidic herbicides are specifically identified as
      targets.

PMID- 17438799
TI  - Determining the extent of biodegradation of fuels using the diastereomers of
      acyclic isoprenoids.
AB  - Improved testing and remediation procedures for sites contaminated with petroleum
      hydrocarbons are a priority in remote cold regions such as Antarctica, where
      costs are higher and remediation times are longer. Isoprenoid/n-alkane ratios are
      commonly used to determine the extent of biodegradation at low levels but are not
      useful once the n-alkanes have been removed. This study demonstrates how the
      diastereomers of the acyclic isoprenoids can be used to determine the extent of
      biodegradation in moderately biodegraded fuel in soils from a bioremediation
      trial at Casey Station, Antarctica. The biological diastereomers of pristane
      (meso; RS = SR) are depleted more rapidly during moderate biodegradation than the
      geological or mature diastereomers (RR and SS), and thus, the ratio of pristane
      diastereomers can determine the level of biodegradation. The statistical
      difference among mean diastereomer ratios for samples grouped according to the
      biodegradation scale and pristane/phytane ratios was highly significant. The
      ratios of norpristane and phytane diastereomers also change with biodegradation
      in a similar fashion, and different levels of sensitivity exist for each.
      Additional benefits are that the method can be performed on conventional gas
      chromatographs by non-specialist chemists and that the ratios are independent of
      evaporation and do not necessarily require a non-biodegraded reference (T0)
      sample. This study details a simple alternative method for determining the extent
      of biodegradation of fuels at moderate levels that can be applied to a wide range
      of petroleum products.

PMID- 17438800
TI  - Analysis of sugars and sugar polyols in atmospheric aerosols by chloride
      attachment in liquid chromatography/negative ion electrospray mass spectrometry.
AB  - Sugars and sugar polyols are relatively abundant groups of water-soluble
      constituents in atmospheric aerosols. This paper describes a method that uses
      liquid chromatography-mass spectrometry (LC-MS) to analyze sugars and sugar
      polyols in atmospheric aerosols, ranging from C3 sugar alcohols to
      trisaccharides. Postcolumn addition of chloroform in acetonitrile was found to
      greatly enhance ionization of these compounds by forming chloride adduct ions in
      the negative-ion mode using electrospray ionization. A gradient elution program
      starting at 5%:95% H20/acetonitrile and ending at 30%:70% H2O/acetonitrile
      provides baseline separations of the sugars and sugar polyols on an amino-based
      carbohydrate column. The detection limits based on quantification of [M + 35Cl]-
      adduct ions were in the order of 0.1 microM. By eliminating the need for
      derivatization, this LC-MS based method provides a simpler alternative method to
      the commonly used and more laborious gas-chromatography based methods. It also
      has an additional advantage of being able to quantify trisaccharide sugars. The
      method was applied to analyze 30 ambient samples of fine particulate matter
      collected at a site away from urban centers in Hong Kong. The sugar compounds
      positively identified and detected in the ambient samples included four sugar
      alcohols (glycerol, erythritol, xylitol, and mannitol), three monosacchride
      sugars (xylose, fructose, and glucose), two disaccharides (sucrose, trehalose),
      two trisaccharides (melezitose, raffinose), and one anhydrosugar (levoglucosan).
      The sum of these sugar and sugar polyol compounds ranged from 38 to 1316 ng m(
      3), accounting for an average of 1.3% organic carbon mass. Through the use of a
      principal component analysis of the ambient measurements, the mono- to
      trisactharide sugars and C3-C5 sugar polyols were identified to be mainly
      associated with soil/soil microbiota while the anhydrosugar (levoglucosan) was
      associated with biomass burning.

PMID- 17438801
TI  - Application of flow cytometry for the assessment of preservation and recovery
      efficiency of bioaerosol samplers spiked with Pantoea agglomerans.
AB  - Exposure assessment of biological aerosols requires trade-offs between efficient
      sampling of airborne microorganisms as either particles or viable units. The main
      objective of this work was to characterize aspects of bioaerosol measurement
      efficiency. A known concentration of the vegetative bacteria Pantoea agglomerans
      was spiked onto different samplers (AGI-30, BioSampler, and membrane filters) and
      then run for increasing time periods using HEPA filtered air. Measurement
      efficiency was evaluated based on total, viable, and culturable counts. Total and
      viable counts were determined by flow-cytometry (FCM); culturable counts were
      evaluated by standard plating. FCM as a method for assaying viability showed
      excellent agreement with known proportions of live/dead organisms (slope = 0.82,
      R(2) = 0.99). P. agglomerans recoveries (total, viable, and culturable) in order
      of best sampler performance included the BioSampler (75%, 52%, and 50%),
      filtration (50%, 13%, and 2%), and the AGI-30 (<30%, 15%, and 5%). The difference
      between viability and culturability provided an indication of viable but
      nonculturable (VBNC) cells. VBNC efficiency for sampling by filter, AGI-30, and
      BioSampler was 80%, 50%, and 100%, respectively. This research helps characterize
      recovery, survival, and culturability efficiencies while sampling environmentally
      sensitive airborne bacteria for purposes of exposure assessment, epidemiologic
      studies, and homeland security.

PMID- 17438802
TI  - Evaporative light scattering: a novel detection method for the quantitative
      analysis of humic-like substances in aerosols.
AB  - The chemical composition of organic atmospheric aerosols is only poorly
      understood. Although a significant fraction of organic aerosols consists of humic
      like substances (HULIS), only little is known about this class of compound, and
      accurate quantification remains difficult, partly due to the lack of appropriate
      standards. Here, evaporative light-scattering detection (ELSD) was applied for
      the first time to quantify water-soluble HULIS in aerosol particles smaller than
      1 microm. This detection method was shown to be suitable for the quantification
      of compounds with unknown structures and lacking appropriate quantification
      standards. As compared to organic carbon determination of isolated HULIS, no
      organic carbon/organic mass (OC/OM) conversion factor needs to be applied with
      ELSD and therefore eliminates this significant uncertainty factor of the OC/OM
      method, which is frequently used to quantify HULIS. Solid-phase extraction and
      size-exclusion chromatography were applied to separate inorganic ions and low
      molecular weight compounds from HULIS before ELSD quantification. The ELSD itself
      provides an additional separation step where low volatility HULIS are separated
      from high volatility, small compounds. Electrospray ionization mass spectrometry
      was used to identify the molecular weight range of the compounds quantified with
      ELSD. The most intensive peaks were in the range of m/z 200-500, with some masses
      upto m/z800. We showed that UV detection using fulvic acid as surrogate
      quantification standard underestimates the HULIS concentration by a factor of 1.1
      to 2.5, which is in agreement with earlier studies. During a 6 week winter 2005
      2006 campaign at a suburban site near Zurich, Switzerland, an average of 1.1
      microg/m(3) HULIS was found, which is about4-6% of the total particle mass
      smaller than 1 microm (PM1) and 10-35% of the organic matter in PM1.

PMID- 17438803
TI  - Source attribution of water-soluble organic aerosol by nuclear magnetic resonance
      spectroscopy.
AB  - The functional group compositions of atmospheric aerosol water-soluble organic
      compoundswere obtained employing proton nuclear magnetic resonance (1H NMR)
      spectroscopy in a series of recent experiments in several areas of the world
      characterized by different aerosol sources and pollution levels. Here, we discuss
      the possibility of using 1H NMR functional group distributions to identifythe
      sources of aerosol in the different areas. Despite the limited variability of
      functional group compositions of atmospheric aerosol samples, characteristic 1H
      NMR fingerprints were derived for three major aerosol sources: biomass burning,
      secondary formation from anthropogenic and biogenic VOCs, and emission from the
      ocean. The functional group patterns obtained in areas characterized by one of
      the above dominant source processes were then compared to identify the dominant
      sources for samples coming from mixed sources. This analysis shows that H NMR
      spectroscopy can profitably be used as a valuable tool for aerosol source
      identification. In addition, compared to other existing methodologies, it is able
      to relate the source fingerprints to integral chemical properties of the organic
      mixtures, which determine their reactivity and their physicochemical properties
      and ultimately the fate of the organic particles in the atmosphere.

PMID- 17438804
TI  - Initial test results for a passive surface water fluxmeter to measure cumulative
      water and solute mass fluxes.
AB  - The theoretical concept and initial test results of a Passive Surface Water
      Fluxmeter (PSFM) to directly and simultaneously measure cumulative water and
      solute mass fluxes in surface water flow systems are presented. The PSFM consists
      of a symmetric hydrofoil that is vertically installed in a stream and one or more
      sorbent columns that are connected to the nonuniform flow field around the
      hydrofoil. Depending on the ambient flow velocity, a flow occurs through each
      column, which elutes portions of initially present "resident" tracers in the
      column, while, at the same time, solutes in the water (e.g., contaminants or
      nutrients) are retained in the sorbent column. Quantification of the resident
      tracer mass remaining and the mass of solutes sorbed in the column enables
      determination of the local cumulative or time-averaged water and solute mass
      fluxes. Laboratory flume experiments show good agreement with independent
      measurements (R(2) > or = 0.96) for instantaneous water fluxes (tested range: 0.3
      0.7 m/s), cumulative water fluxes (50-600 L/cm(2)), and cumulative nitrate fluxes
      (0.4-5.1 g/cm(2)). Future work is required to validate the PSFM performance under
      a larger range of flow velocities, transient flow, and transport conditions and
      for different hydrofoil shapes.

PMID- 17438805
TI  - Extra-cellular polysaccharides, soluble microbial products, and natural organic
      matter impact on nanofiltration membranes flux decline.
AB  - Extra-cellular polysaccharides (EPS), soluble microbiological products (SMP),
      dispersed bacterial cells, and a well-characterized natural organic matter (NOM)
      isolate were observed to determine their influence on the flux decline of model
      nanofiltration membrane systems. Biofouling tests were conducted using bench
      scale, flat-sheet membrane modules, fed with particle-free (laboratory) waters
      and natural waters, some of which were augmented with readily biodegradable
      organic carbon. The modules were operated 6.7 x 10(5) Pa, and 21+/- 2 degrees C.
      Membrane flux-decline was associated with increases in surface EPS mass: between
      30 and 80% of normalized flux decline occurred when membrane-associated EPS
      content increased from 5to 50 microg/ cm2. As judged by standard culturing,
      heterotrophic cell densities recovered from membrane biofilm samples showed no
      significant correlations with the different carbon sources present in the
      feedwaters, or flux decline rates. Results suggested that, in the absence of
      microbiological activity, SMP and NOM have intrinsic membrane fouling properties
      at levels that are operationally significant to commercial-scale membrane
      treatment practices. Results also suggested that SMP may have a biofouling
      potential significantly greater than some types of NOM. Trends obtained relating
      these compounds with flux decline were successfully described by expanding
      existing resistance-in-series models.

PMID- 17438806
TI  - Kinetic analysis of competition between aerosol particle removal and generation
      by ionization air purifiers.
AB  - Ionization air purifiers are increasingly used to remove aerosol particles from
      indoor air. However, certain ionization air purifiers also emit ozone. Reactions
      between the emitted ozone and unsaturated volatile organic compounds (VOC)
      commonly found in indoor air produce additional respirable aerosol particles in
      the ultrafine (<0.1 microm) and fine (<2.5 microm) size domains. A simple kinetic
      model is used to analyze the competition between the removal and generation of
      particulate matter by ionization air purifiers under conditions of a typical
      residential building. This model predicts that certain widely used ionization air
      purifiers may actually increase the mass concentration of fine and ultrafine
      particulates in the presence of common unsaturated VOC, such as limonene
      contained in many household cleaning products. This prediction is supported by an
      explicit observation of ultrafine particle nucleation events caused by the
      addition of D-limonene to a ventilated office room equipped with a common
      ionization air purifier.

PMID- 17438807
TI  - Trichloroethylene uptake into fruits and vegetables: three-year field monitoring
      study.
AB  - Trichloroethylene (TCE) contaminated groundwater migrating into communities
      surrounding Hill Air Force Base (HAFB) in northern Utah prompted a multiyear
      monitoring program (2001-2003) to examine the extent of TCE uptake and transfer
      into edible fruits. During the initial sampling in fall 2001, TCE was detected in
      a small fraction of the 167 fruit and tree core samples collected from 17 private
      residences. Samples were analyzed using headspace gas chromatography (GC) with
      electron capture detection (ECD) with limited confirmation by mass spectrometry
      (MS) in selected ion monitoring mode. In fall 2002, over 300 samples were
      collected from the same general locations sampled in 2001. No TCE was found in
      any of the fruit or vegetable samples above the method detection limit (MDL) for
      the headspace GC/MS method (approximately 0.1 microg/ kg fresh weight, depending
      on sample size), but TCE was again detected in several fruit tree trunk core
      samples. The detection of TCE in fruit in 2001, but not in 2002, may have been
      due to improvements in the analytical procedure or changes in the environmental
      conditions impacting transfer to fruit. The 2003 monitoring focused on repeated
      sampling over several months at five locations that were selected to represent
      the range of exposure scenarios evaluated during the previous years. No TCE was
      identified in any of the fruit above the MDL during 2003, however TCE was again
      found in tree core samples as observed in 2001 and 2002.

PMID- 17438808
TI  - Decolorization of kraft bleaching effluent by advanced oxidation processes using
      copper (II) as electron acceptor.
AB  - Two advanced oxidation processes (AOPs), TiO2/UV/O2 and TiO2/UV/Cu (II), were
      used to remove color from a Kraft bleaching effluent. The optimal decoloration
      rate was determined by multivariate analysis, obtaining a mathematical model to
      evaluate the effect among variables. TiO2 and Cu (II) concentrations and the
      reaction times were optimized. The experimental design resulted in a quadratic
      matrix of 30 experiments. Additionally, the pH influence on the color removal was
      determined by multivariate analysis. Results indicate that color removal was 94%
      at acidic pH (3.0) in the presence of Cu (11) as an electron acceptor. Under this
      condition, the biodegradation of the effluent increased from 0.3 to 0.6.
      Moreover, 70% of COD (chemical oxygen demand) was removed, and the ecotoxicity,
      measured by Daphnia magna, was reduced. Photocatalytic oxidation to remove the
      color contained in the Kraft mill bleaching effluent was effective under the
      following conditions: short reaction time, acidic pH values, and without the
      addition of oxygen due to the presence of Cu (II) in the effluent. Moreover,
      residual Cu (II) was a minimum (0.05.mg L(-1)) and was not toxic to the next
      biological stage. The experimental design methodology indicated that a quadratic
      polynomial model may be used to representthe efficiencyfor degradation of the
      Kraft bleach pulp effluent by a photocatalytic process.

PMID- 17438809
TI  - PCDD/F emissions and distributions in Waelz plant and ambient air during
      different operating stages.
AB  - Significant formation of polychlorinated dibenzo-p-dioxins and dibenzofurans
      (PCDD/Fs) has been observed in a typical Waelz process plant. In 2005, the Waelz
      plant investigated was equipped with a dust settling chamber (DSC), a venturi
      cooling tower, a cyclone (CY), and baghouse filter (BF). In early 2006 activated
      carbon injection (ACI) was adopted to reduce PCDD/F emissions from the plant
      investigated. Samplings of flue gases and ash were simultaneously conducted at
      different sampling points in the Waelz plantto evaluate removal efficiency and
      partitioning of PCDD/Fs between the gas phase and particulates. As the operating
      temperature of the dust settling chamber (DSC) is increased from 480 to 580
      degrees C, the PCDD/F concentration measured at the DSC outlet decreases from
      1220 to 394 ng-l-TEQ/Nm3. By applying ACI, the PCDD/F concentrations of stack gas
      decrease from 139-194 to 3.38 ng-l-TEQ/ Nm(3) (a reduction of 97.6-98.3%) while
      the PCDD/F concentration of reacted ash increases dramatically from 0.97 to 29.4
      ng-l-TEQ/g, as the activated carbon injection rate is controlled at 40 kg/h.
      Additionally, ambient air PCDD/F concentrations were measured in the vicinity of
      this facility during different operating stages (shutdown, and operation with and
      without ACI). The ambient PCDD/F concentration measured downwind and 2.5 km from
      the Waelz plant decreases from 568 to 206 fg-I-TEQ/m(3) after ACI has been
      applied to collect the dioxins. Due to the high PCDD/F removal efficiency
      achieved with ACI + BF, about 24.3 and 3980 ng-l-TEQ/kg EAF-dust treated are
      discharged via stack gas and reacted ash, respectively, in this facility.

PMID- 17438810
TI  - Interrelated effects of aeration and mixed liquor fractions on membrane fouling
      for submerged membrane bioreactor processes in wastewater treatment.
AB  - The interactions of mixed liquor fractions and their impacts on membrane fouling
      were examined at different sparging aeration intensities for submerged hollow
      fiber membrane bioreactors (MBR) in wastewater treatment. The mixed liquor
      samples were fractioned by size into MLSS, colloids quantified by colloidal TOC,
      and dissolved solutes. The experimental results showed that their significance in
      membrane fouling was strongly related to aeration intensity. In the absence of
      sparging aeration, both MLSS and colloids contributed to membrane fouling which
      was further enhanced by their interactions. For the tested membrane module
      operated at the vigorous aeration intensity typically employed in practice,
      however, the deposition of colloids was identified as the most important
      mechanism controlling membrane fouling rates. In contrast, much fewer effects
      were exerted by MLSS: the overall fouling rates were increased initially, and
      then reduced with increasing concentration of MLSS. Thus, the aeration-induced
      turbulence should be considered for properly assessing the mixed liquor fouling
      potential for wastewater MBR processes. Finally, little difference in fouling
      rates was observed with the use of cyclic aeration mode as compared to continuous
      aeration mode.

PMID- 17438811
TI  - Photochemical production of reactive oxygen species by C60 in the aqueous phase
      during UV irradiation.
AB  - The objective of this study was to investigate photochemical production of
      singlet oxygen (1O2) and superoxide radical anion (02*-) by C60 in water. It was
      demonstrated that photoexcited C60 in the aqueous phase efficiently mediated
      transfer of absorbed energy to oxygen and produced singlet oxygen when associated
      with surfactant (Triton X100 and Brij 78) or polymer (polyvinylpyrrolidone),
      which is consistent with previously observed behavior in organic solvents.
      However, when C60 was present as colloidal aggregate suspension, prepared through
      solvent exchange or sonication, this intrinsic character was lost. Similarly, C60
      associated with surfactant mediated electron transfer from electron donor
      (triethylamine) to oxygen producing superoxide radical, while C60 aggregates and
      C60 associated with polymer did not. These results suggestthat the ability of C60
      to mediate energy and electron transfer may be affected by the degree of C60
      aggregation in the aqueous phase as well as characteristics of associated
      stabilizing molecules. Dependence of photochemical reactivity of C60 on its
      dispersion status in the aqueous phase is critical in assessing environmental
      impact and cytotoxicity of this material, as C60 associated with model natural
      organic matter was found to exist in aggregate form and did not produce reactive
      oxygen species under UV irradiation.

PMID- 17438812
TI  - Effect of heavy metals on the sorption of hydrophobic organic compounds to wood
      charcoal.
AB  - Black carbon (BC) is believed to be an important adsorbent of organic pollutants.
      A complex suite of heavy metals and organic pollutants is commonly present in
      many situations. An issue that has received little direct attention is the effect
      of heavy metals on sorption of organic compounds to BC. We found that
      coadsorption of Cu2+ at an environmentally relevant, comparable concentration (50
      mg L-1) decreases sorption of both the polar compound, 2,4-dichlorophenol (DCP),
      and nonpolar compounds, 1,2-dichlorobenzene (DCB) and naphthalene (NAP), by 30
      60%, as measured bythe change in the distribution coefficient (Kd). This was
      attributed to surface complexation of CU2+ to form hydration shells of dense
      water that directly compete with organics for adsorption surface area. In
      contrast, coadsorption of Ag+ increases sorption of the organic solutes, which
      was accounted for by the decline in hydrophilicity of the local region around Ag+
      complexed functionalities due to softness of the cation, leading to mitigated
      competitive sorption of water. Coadsorption of heavy metal ions to nonporous
      graphite, a model of the BC graphene (polycyclic aromatic) structure that has no
      0-containing groups, however, only slightly inhibits organic adsorption due to
      the low affinities of metal ions to graphite surface. The results of the present
      study showed that the presence of coexisting heavy metals greatly affects
      sorption of organic pollutants on BC and thereby their fate and transport.

PMID- 17438813
TI  - Sorption characteristics of polycyclic aromatic hydrocarbons in aluminum smelter
      residues.
AB  - High temperature carbon oxidation in primary aluminum smelters results in the
      release of polycyclic aromatic hydrocarbons (PAH) into the environment. The main
      source of PAH are the anodes, which are composed of petroleum coke (black carbon,
      BC) and coal tar pitch. To elucidate the dominant carbonaceous phase controlling
      the environmental fate of PAH in aluminum smelter residues (coke BC and/or coal
      tar), the sorptive behavior of PAHs has been determined, using passive samplers
      and infinitesink desorption methods. Samples directly from the wet scrubber were
      studied as well as ones from an adjacent 20-year old storage lagoon and roof dust
      from the smelter. Carbon-normalized distribution coefficients of native PAHs were
      2 orders of magnitude higher than expected based on amorphous organic carbon
      (AOC)/water partitioning, which is in the same order of magnitude as reported
      literature values for soots and charcoals. Sorption isotherms of laboratory
      spiked deuterated phenanthrene showed strong (-100 times stronger than AOC) but
      nonetheless linear sorption in both fresh and aged aluminum smelter residues. The
      absence of nonlinear behavior typical for adsorption to BC indicates that PAH
      sorption in aluminum smelter residues is dominated by absorption into the semi
      solid coal tar pitch matrix. Desorption experiments using Tenax showed that fresh
      smelter residues had a relatively large rapidly desorbing fraction of PAH (35
      50%), whereas this fraction was strongly reduced (11-16%) in the lagoon and roof
      dust material. Weathering of the coal tar residue and/or redistribution of PAH
      between coal tar and BC phases could explain the reduced availability in aged
      samples.

PMID- 17438814
TI  - The ROH,UV concept to characterize and the model uv/H202 process in natural
      waters.
AB  - A new concept is introduced to characterize and model the UV/H2O2 advanced
      oxidation process (AOP) in water. Similarto the Rct concept used to describe OH
      radical exposure per ozone dose, the ROH,UV concept is defined as the
      experimentally determined *OH radical exposure per UV fluence. ROH,UV was
      determined by examining the destruction of a probe compound, para-chlorobenzoic
      acid in four different waters: DI water and three natural waters. ROH,UV was
      found to be affected greatly by water quality, specifically background *OH
      radical scavenging, which competed forthe formed *OH radical with the probe
      compound, and background UV absorbance, which screened UV irradiation from the
      hydrogen peroxide. The ROH,UV values determined in the experiments using low
      pressure Hg lamp were greater than those for the medium-pressure Hg lamp .
      Finally, the ROH,UV concept was utilized to calculate an overall scavenging
      factor for each water matrix, and this was successfully utilized in conjunction
      with the steady-state *OH radical model to improve the prediction of the
      oxidation of endocrine-disrupting compounds 17-alpha-ethinyl estradiol and 17
      beta-estradiol in the natural waters.

PMID- 17438815
TI  - Electron transfer from a solid-state electrode assisted by methyl viologen
      sustains efficient microbial reductive dechlorination of TCE.
AB  - The ability to transfer electrons, via an extracellular path, to solid surfaces
      is typically exploited by microorganisms which use insoluble electron acceptors,
      such as iron-or manganese-oxides or inert electrodes in microbial fuel cells. The
      reverse process, i.e., the use of solid surfaces or electrodes as electron donors
      in microbial respirations, although largely unexplored, could potentially have
      important environmental applications, particularly for the removal of oxidized
      pollutants from contaminated groundwater or waste streams. Here we show, for the
      first time, that an electrochemical cell with a solid-state electrode polarized
      at -500 mV (vs standard hydrogen electrode), in combination with a low-potential
      redox mediator (methyl viologen), can efficiently transfer electrochemical
      reducing equivalents to microorganisms which respire using chlorinated solvents.
      By this approach, the reductive transformation of trichloroethene, a toxic yet
      common groundwater contaminant, to harmless end-products such as ethene and
      ethane could be performed. Furthermore, using a methyl-viologen-modified
      electrode we could even demonstrate that dechlorinating bacteria were able to
      accept reducing equivalents directly from the modified electrode surface. The
      innovative concept, based on the stimulation of dechlorination reactions through
      the use of solid-state electrodes (we propose for this process the acronym BEARD:
      Bio-Electrochemically Assisted Reductive Dechlorination), holds promise for in
      situ bioremediation of chlorinated-solvent-contaminated groundwater, and has
      several potential advantages over traditional approaches based on the subsurface
      injection of organic compounds. The results of this study raise the possibility
      that immobilization of selected redox mediators may be a general strategy for
      stimulating and controlling a range of microbial reactions using insoluble
      electrodes as electron donors.

PMID- 17438816
TI  - Structural study of the incorporation of heavy metals into solid phase formed
      during the oxidation of EDTA by permanganate at high pH.
AB  - Properties of solid phases formed during the oxidation of EDTA by permanganate in
      a high-pH, high-ionic strength solution, and the retention of Cu2+, Ni2+, and
      Zn2+ by them were examined. Morphologically, the solids were agglomerates of
      particles with sizes <100 nm. X-ray absorption spectroscopy (XAS) analysis
      indicated that these particles were birnessite. Its precipitation was accompanied
      by the removal of Zn2+ and Cu2+ released as a result of the breakdown of their
      complexes with EDTA. However, Ni2+ was not removed from the supernatant. Cu2+ was
      strongly bound by birnessite and exhibited little mobility in the pH range from 3
      to 14. Zn2+ was more mobile, especially at pH > 12. XAS showed that Cu2+ binding
      sites were located within MnO6 octahedra-comprised sheets that constitute
      birnessite while Zn2+ was positioned between them.

PMID- 17438817
TI  - Household hazardous waste data for the UK by direct sampling.
AB  - The amount of household hazardous waste (HHW) disposed of in the United Kingdom
      (UK) requires assessment. This paper describes a direct analysis study carried
      out in three areas in southeast England involving over 500 households. Each
      participating householder was provided with a special bin in which to place items
      corresponding to a list of HHW. The amount of waste collected was split into nine
      broad categories: batteries, home maintenance (DIY), vehicle upkeep, pesticides,
      pet care, pharmaceuticals, photographic chemicals, household cleaners, and
      printer cartridges. Over 1 T of waste was collected from the sample households
      over a 32-week period, which would correspond to an estimated 51,000 T if
      extrapolated to the UK population for the same period or over 7,000 T per month.
      Details of likely disposal routes adopted by householders were also sought,
      demonstrating the different pathways selected for different waste categories. Co
      disposal with residual household waste dominated for waste batteries and
      veterinary medicines, hence avoiding classification as hazardous waste under new
      UK waste regulations. The information can be used to set a baseline for the
      management of HHW and provides information for an environmental risk assessment
      of the disposal of such wastes to landfill.

PMID- 17438818
TI  - Leaching assessments of hazardous materials in cellular telephones.
AB  - Protocols for assessing the risks of discarded electronic products (e-waste) vary
      across jurisdictions, complicating the tasks of manufacturers and regulators. We
      compared the Federal Toxicity Characteristic Leaching Procedure (TCLP),
      California's Waste Extraction Test (WET), and the Total Threshold Limit
      Concentration (TTLC) on 34 phones to evaluate the consistency of hazardous waste
      classification. Our sample exceeded TCLP criteria only for lead (average 87.4 mg
      L(-1); range = 38.2-147.0 mg L(-1); regulatory limit = 5.0 mg L(-1), but failed
      TTLC for five metals: copper (average 203 g kg(-1); range = 186-224 g kg(-1);
      limit = 2.50 g kg(-1), nickel (9.25 g kg(-1); range = 6.34-11.20 g kg(-1); limit
      = 2.00 g kg(-1)), lead (10.14 g kg(-1); range = 8.2211.60 g kg(-1); limit = 1.00
      g kg-1), antimony (1.02 g kg(-1); range = 0.86-1.29 g kg(-1); limit = 0.50 g kg(
      1)), and zinc (11.01 g kg(-1); range = 8.82-12.80 g kg(-1); limit = 5.00 g kg(
      1). Thresholds were not exceeded for WET. We detected several organic compounds,
      but at concentrations below standards. Brominated flame retardants were absent.
      These results improve existing environmental databases for e-waste and highlight
      the need to review regulatory testing for hazardous waste.

PMID- 17438819
TI  - A new method to determine the ratio of electricity production from fossil and
      biogenic sources in waste-to-Energy plants.
AB  - New directives of the European Union require operators of waste-to-energy (WTE)
      plants to report the amount of electricity that is produced from renewable
      sources in the waste feed. Until now, the standard method to determine the
      portion of renewable electricity is sorting the wastes into defined fractions of
      fossil organic and biogenic waste components and determining the lower heating
      value of these fractions. Out of it the amount of electricity production from
      renewables is calculated. This practice is labor and cost intensive. Therefore,
      it is usually carried out once a year which provides only a snapshot analysis of
      limited significance. This paper proposes a method to calculate the portion of
      electricity produced from renewable materials in waste continuously by solving a
      set of equations. All data required are either available from literature or from
      operating data routinely measured in WTE plants. The advantages are statistically
      derived uncertainty of the result, temporal resolution of the result down to
      daily mean values, low implementation efforts, and virtually no operational
      costs. An example of the implementation of the method to a 60 000 tons per year
      WTE plant is given.

PMID- 17438820
TI  - Ex situ aqueous mineral carbonation.
AB  - The U.S. Department of Energy's National Energy Technology Laboratory (NETL)
      located in Albany, OR (formerly the Albany Research Center) has studied ex situ
      mineral carbonation as a potential option for carbon dioxide sequestration.
      Studies focused on the reaction of Ca-, Fe-, and Mg-silicate minerals with
      gaseous CO2 to form geologically stable, naturally occurring solid carbonate
      minerals. The research included resource evaluation, kinetic studies, process
      development, and economic evaluation. An initial cost estimate of approximately
      $69/ton of CO2 sequestered was improved with process improvements to $54/ton. The
      scale of ex situ mineral carbonation operations, requiring 55 000 tons of mineral
      to carbonate, the daily CO2 emissions from a 1-GW, coal-fired power plant, may
      make such operations impractical.

PMID- 17438821
TI  - Environmental consequences of water pumped from greater New Orleans following
      Hurricane Katrina: chemical, toxicological, and infaunal analysis.
AB  - The U.S. Army Engineer Research and Development Center Environmental Laboratory,
      Vicksburg, MS, conducted a study to determine the extent to which Hurricane
      Katrina floodwaters in the New Orleans, Louisiana area may have had impacts on
      wildlife habitat and other biological resources in surrounding areas. These
      studies were conducted as part of the Interagency Performance Evaluation
      Taskforce, an investigation of environmental impacts originating from the failure
      of the hurricane protection system during Hurricane Katrina. This paper presents
      data regarding the effects of pumped floodwaters on sediment chemistry, toxicity,
      and benthic invertebrate assemblages near pumping stations that discharged
      floodwaters into marshes near Chalmette and Violet, Louisiana. Chemical
      contamination of sediments was observed and varied among sample locations (e.g.,
      outfall locations, wastewater treatment plant, canals, and wetlands); however,
      trends in the chemistry data were not always consistent with bioassay results. A
      comparison of the sediment chemistry data from this study with three other
      studies reporting concentrations of chemicals in sediments within the city of New
      Orleans suggested that sediments and associated contaminants present within the
      levees were not pumped into the marsh in appreciable quantities.

PMID- 17438822
TI  - Monitoring the effects of pulp and paper effluent is restricted in genetically
      distinct populations of common bully (Gobiomorphus cotidianus).
AB  - The common bully (Gobiomorphus cotidianus), a small-bodied New Zealand native
      fish species, was used to monitor population impacts of multiple effluents in the
      Tarawera River, New Zealand. In an initial survey, the absence of reproductive
      development at the expected spawning time for common bullywas observed in a
      population downstream of effluent discharges. Subsequently, we examined the
      hypotheses that the observed changes were due to effluent exposure, migratory
      patterns, or genetic differences between populations. Liver detoxification enzyme
      activity and stable isotopes provided evidence against upstream migration of
      sexually mature bully. The observed presence of developed gonads in the
      downstream population during winter season resulted in the rejection of the
      hypothesis that reproductive failure was due to effluent exposure, and itwas
      concluded that there were substantial differences in reproductive timing. Genetic
      analyses of two upstream, one downstream, and one population from a nearby
      coastal river indicated the upstream (reference) and downstream (effluent
      exposed) bully in the river formed genetically distinct populations. The
      identification of a nearby river population with similar reproductive timing and
      high genetic similarity to the effluent-exposed population suggests that the
      observed differences in the genetics of the downstream population were not caused
      by effluent exposure. The genetic analysis did highlight the lack of downstream
      dispersion and gene flow in the river which could possibly be related to
      anthropogenic stress.

PMID- 17438823
TI  - Analytical and functional characterization of microcystins [Asp3]MC-RR and
      [Asp3,Dhb7]MC-RR: consequences for risk assessment?
AB  - The microcystin (MC) producing P. rubescens occurs in pre-alpine lakes and may
      impact fishery success, bathing, and raw water quality. P. rubescens extracts,
      characterized via LC-MS, contained the two MC-RR variants [Asp3]MC-RR and
      [Asp3,Dhb7]MC-RR. The protein-phosphatase-inhibition assay (cPPIA with
      phosphatases 1 and 2A) in its capability to quantify [Asp3]MC-RR, [Asp3,Dhb7]MC
      RR, and MC-RR was compared to HPLC-DAD and anti-Adda-ELISA. The IC50 values (PP1
      and PP2A) determined for MC-LR, MC-RR, and [Asp3]MC-RR were in the same range
      (1.9-3.8 and 0.45-0.75 nM). A 50-fold higher concentration of [Asp3,Dhb7]MC-RR
      (29.8 nM) was necessary to inhibit the PP2A by 50%. The PP1-IC50 of [Asp3,Dhb7]MC
      RR was 22-fold higher (56.4 nM) than those of the other MCs, suggesting that
      specific structural characteristics are responsible for its weaker PPI capacity.
      Western blots demonstrated that [Asp3,Dhb7]MC-RR does not covalently bind to PP1.
      [Asp3,Dhb7]MC-RR has comparable in vivo LD50 values to MC-RR, despite a far lower
      PP-inhibiting capacity, suggesting that toxicodynamic and toxicokinetic
      characteristics of [Asp3,Dhb7]MC-RR are responsible for its high in vivo
      toxicity. The data demonstrate that cPPIA analysis of [Asp3,Dhb7]MC-RR-containing
      samples prevent reliable MC determination and lead to underestimation of
      potential toxicity.

PMID- 17438824
TI  - Single cell level microalgal ecotoxicity assessment by confocal microscopy and
      digital image analysis.
AB  - In ecotoxicological studies involving environmental contaminants, rapid and multi
      parametric optical detection based methods have definite advantages over
      traditional growth inhibition assays. In this context, a confocal laser scanning
      microscopy (CLSM) based method to assess ecotoxicity arising out of biocide
      insult to marine microalgae is reported. Using this technique, the effect of in
      use concentrations of chlorine (an oxidizing biocide) on a marine diatom
      (Cocconeis scutellum Ehrenb) was determined based on inhibition of chlorophyll
      autofluorescence and esterase activity (probed by fluorescein diacetate (FDA)
      staining). Determination of mean fluorescence intensity (MFI) per cell by
      collecting auto-fluorescence from single cells in x, y and z dimensions permitted
      reproducible toxicity evaluation at single-cell level. Chlorine-induced
      inhibition of autofluorescence in laboratory cultures was dose-dependent.
      Additional data on metabolic activity of the diatom cells following chlorine
      exposure was collected by FDA staining. Our results demonstrate that chlorine, an
      antifouling biocide commonly used in cooling water systems, causes significant
      reduction in chlorophyll autofluorescence and esterase activity in diatoms in
      short-term exposure experiments. Tests employing multiple organisms and multiple
      toxicity endpoints are superior to standard algal growth inhibition assays for
      they provide a better understanding of algal-algal interactions and real impact
      in the environment. The combined autofluorescence-FDAtechnique described here is
      rapid and has clear advantages in terms of using environmentally relevant
      toxicant and cell concentrations. Additional microalgal species and toxicity end
      points can be employed in order to develop multi-species and multiparameter
      bioassay using confocal microscopy.

PMID- 17438825
TI  - Toxicity of parked motor vehicle indoor air.
AB  - The interior of motor vehicles is made of a wide variety of synthetic materials,
      which emit volatile organic compounds (VOC). We tested the health effects of
      emissions from vehicles exposed to "parked in sunshine" conditions. A new and a 3
      year old vehicle with identical interior were exposed to 14 000 W of light.
      Indoor air was analyzed by GC-MS. Toxicity of extracts of indoor air was assayed
      in human primary keratinocytes, human lung epithelial A549 cell line, and Chinese
      hamster V79 lung fibroblasts. In addition, toxicity after metabolic activation by
      CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2B6, and CYP2E1 was assayed. The effect on
      type I allergic reaction (IgE-mediated immune response), type IV allergic
      reaction (T-cell mediated immune response), and irritative potential was
      evaluated also. A total of 10.9 and 1.2 mg/m(3) VOC were found in new and used
      motor vehicle indoor air, respectively. The major compounds in the new vehicle
      were o,m,p-xylenes, C3 and C4-alkylbenzenes, dodecane, tridecane, and
      methylpyrrolidinone. In the used vehicle they were acetone, methylpyrrolidinone,
      methylcyclohexane, acetaldehyde, o,m,p-xylenes, ethylhexanol, and toluene. No
      toxicity was observed in any cell line with or without metabolic activation.
      Neither did we find an effect on type IV sensitization or an irritative
      potential. A slight but statistically significant aggravating effect on IgE
      mediated immune response of only the new vehicle indoor air was determined (p <
      0.05). The IgE-response modulating effect of indoor air might be relevant for
      atopic individuals. Else no direct toxicity, no toxicity after metabolic
      activation by cytochrome P450, and no irritative or type IV sensitizing potential
      of motor vehicle indoor air were found, neither from the new nor used vehicle.
      Our investigations indicated no apparent health hazard of parked motor vehicle
      indoor air.

PMID- 17438826
TI  - A screening level index for assessing the impacts of veterinary medicines on dung
      flies.
AB  - Veterinary parasiticides are administered to livestock to control a wide range of
      parasites. Following excretion, these substances may persist in the environment
      and impact nontarget organisms. This paper describes a simple screening-based
      index for predicting the effects of veterinary parasiticides on dung flies using
      data on parasiticide toxicity, animal husbandry, and parasiticide use. The
      utility of the index has been assessed, at the farm scale for a number of
      dipteran species, using data from a survey of farms in England and insect ecology
      and ecotoxicological data. The results indicate that a large proportion (35%) of
      parasiticide treatments in England will have no impact on dung fly populations.
      In terms of individual parasiticides, the macrocyclic lactone doramectin was
      predicted to have the highest impact on English dipteran populations with a
      maximum reduction in the population of horn flies on one farm of 28%. Ivermectin
      pour-on had the next highest impact (6.8%), followed by eprinomectin (6.4%), and
      ivermectin injection (4.1%). Due to a lack of data, it was not possible to assess
      the effects of the benzimidazole parasiticides (oxfendazole and fenbendazole),
      morantel and permethrin. The approach is simple, nondata-intensive and has the
      potential to be a valuable tool for use in environmental risk assessment or
      management of new and existing veterinary parasiticides.

PMID- 17438827
TI  - Effect of a fullerene water suspension on bacterial phospholipids and membrane
      phase behavior.
AB  - Several fullerene-based nanomaterials generate reactive oxygen species that can
      damage cells. In this study, we investigated the effect of buckminsterfullerene
      (C60) introduced as colloidal aggregates in water (nC60) on bacterial membrane
      lipid composition and phase behavior. Pseudomonas putida (Gram-negative) and
      Bacillus subtilis (Gram-positive) responded to nC60 by altering membrane lipid
      composition, phase transition temperature, and membrane fluidity. P. putida
      decreased its levels of unsaturated fatty acids and increased the proportions of
      cyclopropane fatty acids in the presence of nC60, possibly to protect the
      bacterial membrane from oxidative stress. Fourier transform infrared spectroscopy
      measurement of intact bacterial cells showed slightly increased phase transition
      temperatures (Tm) and increased membrane fluidity for cells grown in the presence
      of high, growth-inhibiting concentrations (0.5 mg L(-1)) of nC60. B. subtilis
      responded to a low dose of nC6o (0.01 mg L(-1)) by significantly increasing the
      levels of iso- and anteiso-branched fatty acids (from 5.8 to 31.5% and 12.9 to
      32.3% of total fatty acids, respectively) and to a high, growth-inhibiting
      concentration of nC60 (0.75 mg L-1) by increasing synthesis of monounsaturated
      fatty acids. In contrast to P. putida, B. subtilis response was a decrease in Tm
      and an increase in membrane fluidity. These findings represent the first
      demonstrated physiological adaptation response of bacteria to a manufactured
      nanomaterial, and they showthat response inlipid composition and membrane phase
      behavior depends on both the nC60 concentration and the cell wall morphology.

PMID- 17438828
TI  - Novel estrogen receptor-related Transcripts in Marisa cornuarietis; a freshwater
      snail with reported sensitivity to estrogenic chemicals.
AB  - We have isolated novel molluskan steroid receptor transcripts orthologous to
      vertebrate estrogen receptors (ERs) and estrogen receptor-related receptors
      (ERRs) from the freshwater snail Marisa cornuarietis. Radiolabeled ligand binding
      analyses showed that neither recombinant receptor protein specifically bound
      17beta-estradiol over the range applied (0.3-9.6 nM). These novel receptor
      transcripts have thus been designated mcER-like and mcERR respectively.
      Quantitative PCR revealed mcER-like to be expressed ubiquitously throughout a
      range of male and female structures studied, including neural and reproductive
      tissues. Highest absolute levels were seen in the male penis-sheath complex. The
      mcERR mRNA was also expressed ubiquitously throughout all male and female tissues
      analyzed here, with very low absolute transcript numbers in female accessory sex
      structures compared to other tissues.

PMID- 17438829
TI  - Comment on "antibiotic resistance genes as emerging contaminants: studies in
      northern Colorado".

PMID- 17438830
TI  - Atopy patch test in the diagnosis of food allergy in children with atopic
      dermatitis.
AB  - Atopic eczema/dermatitis syndrome (AEDS) is one of the most common chronic
      allergic diseases in children. Among the allergens found to be relevant in AEDS,
      aeroallergens and food allergens are the most important. The exposure of these
      patients to their relevant protein allergens can trigger an exacerbation or
      maintain the disease. AEDS is frequently associated with food allergy, which
      complicates the management in approximately 40% of these children. Atopy patch
      test (APT) can help in detecting food allergies in children with AEDS. The
      earliest publication on patch testing in eczema was described in 1937 by
      Rostenberg, but the first controlled clinical trial was provided by Mitchell in
      1982. APT with food allergens were introduced into clinical use in 1996 by the
      group of Isolauri. APT test is performed epicutaneously with typical immediate
      type allergens (aeroallergens or foods). As a number of apparently minor test
      modifications greatly influence the sensitivity, specificity, and reproducibility
      of the APT, the European Task Force on Atopic Dermatitis (ETFAD) has developed a
      standardized APT technique. APT has developed into a valuable additional tool in
      the diagnostic work-up of food allergy in infants and children with atopic
      dermatitis.

PMID- 17438831
TI  - PAR index in the evaluation of the stability of the orthodontic treatment
      results. A review.
AB  - The evaluation of the treatment results is normally done to estimate the nature
      and quality of work, so that justice can be done to the work that we do and also
      that the patients will be satisfied. The primary motive of every orthodontist
      should be to treat the patient effectively and successfully with long lasting
      results. Thus the patients are to be assessed, using an appropriate method. PAR
      index was developed in the recent years to evaluate the treatment results and it
      is considered as a simple, objective and a reliable manner for evaluating the
      stability after orthodontic treatment. The index can be applied to different
      components of the dentition and scores are applied to each component after which
      the individual scores are multiplied with their respective weightings to balance
      the impact of the individual components of the overall result. They are then
      summed up to establish an overall total. In this manner, the method was carried
      out for the study casts of the three different phases of the treatment i.e.
      before the onset of the treatment, immediately after treatment and 2 years after
      treatment for assessing the stability after orthodontic treatment.

PMID- 17438832
TI  - Evaluation of the stability after orthodontic treatment using PAR index.
AB  - The aim of the present study is to establish the results using the scores
      obtained from the methodology that was applied for assessing the stability after
      2 years post orthodontic treatment and stability in a sample of 69 individuals.
      After applying PAR index to the collected group of patients, a series of scores
      were obtained, which were then needed to be evaluated further to establish the
      results. The scores were evaluated using the nomogram. A comparison was done
      between the post treatment and the 2 years post treatment PAR weighting scores to
      determine if the results were stable after orthodontic treatment. The majority of
      the orthodontic patients were treated to a good standard and that the results
      appeared to be stable.

PMID- 17438833
TI  - Our approach to the spastic hip subluxation and dislocation in children with
      cerebral palsy.
AB  - The purpose of this study was to evaluate the effectiveness of our approach to
      the spastic hip subluxation and dislocation in children with cerebral palsy. We
      evaluated 56 hips in our consecutive patients who had been operated on at our
      department between January 2003 and December 2005. There were done soft-tissue
      release procedures in 42 hips, osseous reconstructive surgery in 11 hips and
      osseous palliative surgery in 3 hips. The duration of follow-ups was 1-3 years
      after surgery. We achieved good result in 15 hips after soft-tissue release,
      fifteen hips had a fair result, nine a poor result and three a failure. No
      redislocation was observed after osseous surgery in our patients. Two patients
      observed no pain after osseous palliative surgery, transient pain in the hip was
      in one case. In all hips the range of motion (abduction) was increased. The
      personal hygiene and possibilities of rehabilitation were improved. Childhood is
      the optimal time to intervene to maximize the function of the patient with
      cerebral palsy. The musculoskeletal treatment of the child prevents future
      problems with pain and deformity.

PMID- 17438834
TI  - Paleopathological findings of dry skulls with plagiocephaly.
AB  - In literature, plagiocephaly is defined as abnormal asymmetrical head shape with
      unilateral flattening of the anterior and/or posterior part of the skull. It is
      classified as synostotic or deformational. Synostotic plagiocephaly is the result
      of premature unilateral fusion of neurocranim sutures. Positional plagiocephaly
      is caused by asymmetrical intrauterine and/or postnatal external forces. The
      authors report findings of both types of plagiocephaly in the dry skull
      collection from pertaining Broumov Ossuary (13th-18th century), Czech Republic.
      In the paper, the incidence of paleopathological asymmetrical skull deformities
      is discussed in the context with recent clinical data.

PMID- 17438835
TI  - Lithium microdialysis and its use for monitoring of stomach and colon submucosal
      blood perfusion--a pilot study using ischemic preconditioning in rats.
AB  - During shock, exposure of gut to ischemia determines patient's survival. Ischemic
      preconditioning (ISP) elevates nitric oxide and blood perfusion, whereby it
      protects organs against subsequent severe ischemia/reperfusion. Using appropriate
      flow marker, microdialysis may serve to monitor interstitial microcirculation.
      Hence, our aim was to test the reliability of lithium as a flow marker (lithium
      microdialysis, LM) on an ISP model. Rats were divided into three groups. Two
      (ischemic and preconditioned) groups underwent 30 min celiac artery occlusion
      (CAO) with 2.5 h reperfusion. 25 min before CAO, the latter experienced 5 min
      ischemia. Sham-operated animals served as controls. LM in stomach and colon
      submucosa, serum nitric oxide, hepatic and pancreatic enzymes were measured. In
      stomach, LM indicated a decrease in blood perfusion evoked by CAO (p < 0.01) in
      both experimental groups. During reperfusion, the ischemic animals showed a
      restoration of microcirculation, unlike the preconditioned ones, whose blood
      perfusion failed to regenerate (p < 0.001). For any group, LM showed no
      microcirculation modification in colon. Serum analytes remained unchanged. We
      conclude that LM appears to be a potentially suitable indicator of
      gastrointestinal interstitial microcirculation. However, we failed to demonstrate
      any beneficial effect of ISP on pancreas, systemic nitric oxide and local/remote
      microcirculation within studied organs.

PMID- 17438836
TI  - Reactivation potency of new group of acetylcholinesterase reactivators and their
      comparison with currently available oximes.
AB  - In this work, in vitro potency of novel serie of monoquaternary pyridinium oximes
      to reactivate cyclosarin-inhibited acetylcholinesterase (AChE) was tested.
      Currently available oximes (pralidoxime, obidoxime, trimedoxime, HI-6 and BI-6)
      were used as oximes for comparison. As resulted, none of tested new reactivators
      was able to reactivate AChE inhibited by cyclosarin. Also pralidoxime, obidoxime
      and trimedoxime did not reach good reactivation results. Only oximes HI-6 and BI
      6 achieved sufficient reactivation potency. From obtained results, it can be
      deduced, that only reactivators with oxime group in position two are able to
      reactivate cyclosarin-inhibited AChE.

PMID- 17438837
TI  - Frequency of neonatal hypoglycemia in large for gestational age infants of non
      diabetic mothers in a community maternity hospital.
AB  - Large for gestational age (LGA) infants are at increased risk for hypoglycemia.
      The aim of the study was to determine the frequency of neonatal hypoglycemia in
      LGA infants of non-diabetic mothers in a Community Maternity Hospital in
      Gaziantep, Turkey. Hospital records of 5229 infants of non-diabetic mothers were
      examined retrospectively. Newborns with birth weight more than 4000 g were
      defined as LGA. The control group consisted of 100 appropriate for gestational
      age (AGA) newborns. Capillary blood glucose was measured at the second hour of
      life. Glucose values lower than 40 mg/dL (2.2 mmol/L) were defined as
      hypoglycemia. Ninety-six (1.8%) of the 5229 infants were found to be LGA. The
      mean capillary glucose levels of the LGA newborns were significantly lower than
      those of the AGA newborns (54 mg/dL (3.0 mmol/L) vs. 95 mg/dL (5.2 mmol/L), p <
      0.0001). Neonatal hypoglycemia was established in 16 of 96 LGA infants (16.7%).
      In the control group hypoglycemia was absent. The rate of hypoglycemia in LGA
      infants was significantly higher than the rate in the AGA infants (p = 0.0000).
      As hypoglycemia is not rare in LGA infants and can have serious consequences,
      blood glucose levels should be screened routinely in LGA infants.

PMID- 17438838
TI  - Asymptomatic aneurysmal portosystemic venous shunt: a case report and review of
      the literature.
AB  - Spontaneous intrahepatic portosystemic venous shunt (SIPSVS) is relatively rare
      and not well recognized. Herein, we report 75-year-old female of an aneurysmal
      portosystemic venous shunt detected by colour Doppler ultrasound in check-up
      examination. A direct vascular communication between left portal vein and middle
      hepatic vein was confirmed by CT-angiography. The cause of intrahepatic
      portosystemic venous shunt is disputed. This abnormality, mainly described in
      cirrhotic liver and rarely in healthy liver, is usually revealed by hepatic
      encephalopathy or glycoregulation disorders. However, with improvements in
      imaging the number of reports of SIPSVS identified incidentally in patients
      without definite symptoms increasing.

PMID- 17438839
TI  - Nitric oxide and systemic sclerosis.

PMID- 17438840
TI  - [Surgical approaches of anterior skull base tumors].
AB  - OBJECTIVE: Study for surgical approaches on anterior skull base tumors. METHOD:
      All 37 cases with anterior skull base tumors were surgically treated. Twenty-one
      cases were treated with anterior craniofacial approaches: Frontal subcranial
      combined with total maxillectomy in 8 cases or/with orbital exenteration in 5
      cases, combined with lateral rhinotomy in 1 cases, combined with naso
      translocation with medial maxillectomy in 7 cases. Partial or total maxillary
      swing combined with naso pyramid translocation in 13 cases. Frontonasal, fronto
      orbital and midface degloving in one case respectively. RESULT: Of the 27
      malignant cases the 3 and 5-year survival rates were 81.9% (22/27) and 62.9%
      (17/27) respectively, and one tumor free case living well more than 9 years.
      There were no recurrence in 10 cases with benign tumor. CONCLUSIONS: Various
      craniofacial approaches except lateral rhinotomy provide directly satisfactory
      tumor exposure and facilitate enbloc resection of the naso paranasal sinus tumor
      with intracranial extension. Partial or total maxillary swing combined with naso
      pyramid translocation is good for tumor involving the skull base without
      intracranial invasion. The fronto-nasal pyramid translocation is good for removal
      of the upper part of nasal tumor with intracranial extension on well developed
      frontal sinus. The fronto orbital approach is proper for removal of fronto
      sphenoid tumor and midface degloving may be used in selected cases.

PMID- 17438841
TI  - [Resection tumor of the anterior skull base region with extend external frontal
      sinus approach].
AB  - OBJECTIVE: To study a better surgical approach for the resection of tumor in the
      anterior skull base and the fronto-orbito-ethmoidal region. METHOD: Extend
      external frontal sinus approach was made in the lesion side. The incision can be
      extended outward to the nasal side or superciliary arch according to the tumors
      extent and size so as to get a full exposure of tumors of anterior skull base,
      fronto-orbito-ethmoidal region, or exterior margin of arcola. RESULT: From
      January 1998 to December 2003, 28 patients suffered tumors of anterior skull base
      and fronto orbito-ethmoidal region were received tumors resection through this
      approach. Postoperatively, no death or recurrence have occurred up to now in 8
      cases of benign tumors, and the one-year survival rate was 95% (19/20), the three
      year survival rate was 61.5% (8/13), and the five-year survival rate was 57.1%
      (4/7) in 20 cases of malignant tumors. CONCLUSION: This approach provide good
      exposure. Bleeding is little, operation field is clear, operating is easy re
      establish skull base is convenience, surgical trauma is small, and reaction is
      mild when using decohesion tumors and block blood supply in skull base method. We
      believe this approach is a better method for resection of tumors in anterior
      skull base and the fronto-orbito-ethmoidal region.

PMID- 17438842
TI  - [The perioperative glycemic control in chronic rhinosinusitis coexisting
      diabetes].
AB  - OBJECTIVE: To evaluate the method of the perioperative blood glucose control in
      chronic rhinosinusitis coexisting diabetes. METHOD: Twenty-two cases of chronic
      rhinosinusitis coexisting diabetes were investigated retrospectively, including
      one case of type 1 diabetes and 21 cases of type 2 diabetes. The study cohort was
      divided into two groups, the one was complication group and the other was non
      complication group. The patients in complication group were injected insulin to
      control blood glucose level, and the patients in non-complication group were
      prescribed oral medicine. RESULT: Blood glucose levels below 9.0 mmol/L in
      complication group and below 7.0 mmol/L in non-complication group were both the
      surgical indication for the patients in this research cohort. Twenty-one cases
      were completely recovered and one case made progress significantly. CONCLUSION:
      The detection of blood and urine glucose levels must be the routine item before
      the nasal endoscopic surgery. To control blood glucose levels in type 2 diabetes
      with non-complication, oral medicine is the first choice, in type 1 diabetes and
      type 2 diabetes with complication, insulin should be first considered.

PMID- 17438843
TI  - [Analysis of sphenoid sinus malignant tumor misdiagnosis].
AB  - OBJECTIVE: To investigate the clinical characteristics, therapeutic efficacy and
      misdiagnosis status of sphenoid sinus malignant tumor in order to improve the
      diagnosis rate. METHOD: Analysing and summarizing 18 patients with sphenoid sinus
      malignant tumor in our department from 1996 to 2005. RESULT: The metastatic
      nasopharyngeal carcinoma is the most of sphenoid sinus malignant tumor,the second
      is chordocarcinoma and non-Hodgkin lymphoma, its clinical manifestation was
      headache (78%), sight alteration (50%), cranial nerve palsy (39%), nose bleed
      (11%); the clinical diagnosis rate was 56%. CONCLUSION: The nasal endoscopy is
      the convention examination for these patients with sphenoid sinus malignant tumor
      whose imageology diagnosis is of limitation.

PMID- 17438844
TI  - [The application, observation and discussion of indications about no packing
      after ESS].
AB  - OBJECTIVE: To study the safety and feasibility after functional Endoscopic
      surgery(FESS), without no nasal packing in 74 patients,compare these patients
      with 20 packing patients, and discuss the possibility and indication of avoiding
      packing. METHOD: No nasal packing after FESS in 74 patients, the measures had
      been taken to reduce postoperative bleeding including appropriate case-chosen,
      medical administration before and after operation, alleviation of trauma in
      operation, and meticulous sinus clearance to prevent synechia. RESULT: The
      postoperative blood loss were less than 50 ml. No bleeding complication happened
      out of the 74 no-packing patients, the blood exudation ceased timely after FESS.
      CONCLUSION: The nasal packing could be avoided in the majority of FESS through
      proper management. This choice will reduce the discomfort and the cost of the
      patients who have to receive FESS procedure, and increase their compliance.

PMID- 17438845
TI  - [Measurement of components of the phospholipid of the surfactant in irrigating
      fluid from the nasopharynx of patients with chronic sinusitis].
AB  - OBJECTIVE: To investigate the effect of chronic sinusitis on components of the
      phospholipid of nasopharyngeal surfactant, and to study biochemical component of
      phospholipid of surface active substance. METHOD: The concentrations of
      surfactant in nasopharyngeal irrigating fluid were implemented in normal controls
      and patients with chronic sinusitis. Components of phospholipid such as
      Phosphatidylserine, Phosphatidylethanolamine, Phosphatidylcholine and
      Sphingophospholipid were measured by the high-performance liquid chromatograph.
      RESULT: Results showed as follows (1) There was surfactant in nasopharynx. 4
      compositions of phospholipid could be measured. (2) Compared with controls,
      Phosphatidylserine signficantly decreased in patients with chronic sinusitis (P <
      0.05). (3) Only Phosphatidylserine signficantly decreased between sinusitis III
      stages and controls (P < 0.05). The rests had no signficant difference between
      chronic sinusitis' stages and controls, and among stages. But as the chronic
      sinusitis' stages proceeded, proportion of Phosphatidylserine may decreased.
      CONCLUSION: (1) There is surfactant in nasopharynx, nasopharyngeal surfactant is
      made of Phosphatidylserine, Phosphatidylethanolamine, Phosphatidylcholine and
      Sphingophospholipid. The proportion of Phosphatidylcholine shows most, and
      determines biochemical effect of nasopharyngeal surfactant. (2) chronic sinusitis
      may cause decrease of some components of nasopharyngeal surfactant. (3) As the
      chronic sinusitis' stages proceed, the proportion of some phospholipids
      progressively decrease. Which, above assessed, may cause the change of surfactant
      in eustachian tube, and cause dysfunction of middle ear and eustachian tube.

PMID- 17438846
TI  - [Analysis of 167 postnasal drip syndromes ambulatory treatment].
AB  - OBJECTIVE: Carry out analysis on to diagnosing the result that the patient cures
      for postnasal drip syndrome cases, discuss the disease curing method. METHOD: One
      hundred and sixty-seven patients who diagnosed postnasal drip syndrome makes a
      definite diagnosis that the patient adopt a decongestant, part system such as
      using glucocorticoid, improving the sticky film cilium function treats. RESULT:
      All above follow-up of one-hundred and sixty-seven example patients three mouths.
      With subjectivity, if symptom improve action appraises an index, there are 153
      cases have different improve. Fourteen cases don't feel their symptom improved
      obviously. Have efficiency amounting to 94%. CONCLUSION: Despite of Postnasal
      drip syndrome cause of disease complicated. If it is cured by systemic
      medication, it will get ideal therapeutic efficacy.

PMID- 17438847
TI  - [Clinical analysis of rhinogenous ophthalmocele].
AB  - OBJECTIVE: To investigate the diagnosis and treatment of rhinogenous
      ophthalmocele, to reduce misdiagnosis and missed diagnosis rate. METHOD: Sixty
      two patients with rhinogenous ophthalmocele disease in our hospital from January
      1998 to October 2005 were retrospectively analyzed. RESULT: Sixty-two patients
      with rhinogenous ophthalmocele disease, 18 frontal-ethmoid sinus cystic, 12
      nasosinusitis, 6 fungal frontal sinusitis, 10 maxillary sinus carcinoma, 4
      olfactory nerve tumour, 6 traumatic carotid cavernous fistula, 6 ethmoidal sinus
      osteoma. The rhinogenous ophthalmocele caused by frontal-ethmoid sinus cystic and
      nasosinusitis and ethmoidal sinus osteoma were cured. The maxillary sinus
      carcinomas were followed up for 5 years, 2 examples are alive, 2 examples are
      lost. The olfactory nerve tumours were death in 2 years after operation. The 2
      traumatic carotid cavernous fistula were death, 4 were cured. CONCLUSION: The
      disease with rhinogenous ophthalmocele was easily misdiagnosed for the low
      incidence of the disease. According to eyes reasons of ophthalmocele, choose the
      suitable operational method, it is satisfied with the result of treatment.

PMID- 17438848
TI  - [The role of protein kinase C and activator protein-1 signal cascade in the
      regulation of expression of interleukin-5 in T lymphocyte of allergic rhinitis].
AB  - OBJECTIVE: To explore the role of protein kinase C (PKC) and activator protein-1
      (AP-1) in the signal transduction cascade in the expression of interleukin-5 (IL
      5) by peripheral blood T lymphocytes from allergic rhinitis. METHOD: Twenty-five
      allergic rhinitis patients and twenty-three deflection of nasal septum(DNS)
      persons in the study. T lymphocytes were isolated and purified from peripheral
      blood of each person and randomly divided into 3 groups: group A, blank (DNS and
      AR); group B, PKC excitomotor 12-myristate 13-acetate (DNS PMA and AR PMA); group
      C , PMA and curcumin (DNS PMA/curcumin and AR PMA/curcumin). ELISA was used to
      assess the expression of IL-5 in supernatants, and immunocytochemical staining
      for the activation of AP-1. RESULT: The percentage of cells of active AP-1, IL-5
      protein in supernatants of allergic rhinitis T lymphocytes stimulated with PMA
      were significantly higher than those of allergic rhinitis T lymphocytes
      stimulated without PMA (P < 0.01) and with PMA and curcumin (P < 0.01); than
      those of deflection of nasal septum T lymphocytes stimulated with PMA (P < 0.01),
      with PMA and curcumin (P < 0.01) and without PMA. The percentage of cells of
      active AP-1, IL-5 protein in supernatants of allergic rhinitis T lymphocytes
      stimulated with PMA and curcumin were significantly lower than those of allergic
      rhinitis T lymphocytes stimulated with PMA (P < 0.01); but significantly higher
      than those of allergic rhinitis T lymphocytes stimulated without PMA and those of
      deflection of nasal septum T lymphocytes stimulated. There were good positive
      correlation between the percentage of cells of active AP-1 and IL-5 protein in
      supernatants (r = 0.92, P < 0.01). CONCLUSION: AP-1 may participate in the signal
      transduction of PKC-triggered expression of IL-5 in allergic rhinitis T
      lymphocytes. This suggests the activation of PKC/AP-1 signal transduction cascade
      of T lymphocytes may play an important role in the pathogenesis of allergic
      rhinitis.

PMID- 17438849
TI  - [Expression and significance of Eotaxin and Eotaxin-2 in nasal polyposis and
      nasal polyp tissue].
AB  - OBJECTIVE: To study the expression of Eotaxin and Eotaxin-2 in nasal polyposis
      and nasal polyp and explore the different mechanism between polyposis and polyp.
      METHOD: Fifteen cases of nasal polyposis, thirteen cases of polyp and eight cases
      of normal middle turbinate were studied with immunohistochemical SP method to
      detect the expression of Eotaxin and Eotaxin-2. RESULT: There were significant
      differences between either two groups about the expression of Eotaxin-2 (P <
      0.05). The expression of Eotaxin in nasal polyposis and polyp were dramatically
      higher than in controls (P < 0.05), the expression of Eotaxin between nasal
      polyposis and polyp was no remarkable difference (P > 0.05). CONCLUSION: Both of
      Eotaxin and Eotaxin-2 likely play key roles in the inflammatory reaction process
      of nasal polyposis and polyp. The different expression of Eotaxin-2 between nasal
      polyposis and polyp demonstrates it may be one of the main causes in the
      different mechanism of the two diseases.

PMID- 17438850
TI  - [Effects of systemic corticosteroids on expression of Eotaxin in nasal polyps].
AB  - OBJECTIVE: To observe the effects of systemic corticosteroids on the expression
      of Eotaxin in nasal polyps. METHOD: The SP immunohistochemical methods were
      applied to detected the expression of Eotaxin in nasal polyps before and after
      corticosteroids therapy. The optical density of positive cells in mucosal
      epithelia, vascular endothelia, inflammatory cells was measured by using HPIAS
      2000 image-conduct system. RESULT: The expression of Eotaxin was positive in the
      cytoplasm of the mucosal epithelia,the inflammatory cells and the vascular
      endothelia in nasal polyps. The expression of Eotaxin was significantly reduced
      in the mucosal epithelia, the inflammatory cells and the vascular endothelia of
      nasal polyps after treated with corticosteroids compared with pre-treated.
      CONCLUSION: Inhibiting the expression of Eotaxin in mucosal epithelia,
      inflammatory cells and vascular endothelia of nasal polyps, reducing recruitment
      and activation of eosinophil and relieving eosinophil inflammatory reaction in
      nasal polyps may be one of mechanisms of systemic corticosteroids therapy on the
      nasal polyps.

PMID- 17438851
TI  - [Nasal vestibular cyst: a report of forty two cases and investigation of its
      pathogenesis].
AB  - OBJECTIVE: To investigate the pathogenesis of nasal vestibular cyst. METHOD:
      Forty two case of nasal vestibular cyst were retrospectively analyzed, including
      clinical manifestation, pathological findings, surgical therapy efficacy. RESULT:
      Of these 42 cases of the type of lining epithelia, pseudostratified columnar
      epithelium was identified in 24 cases, stratified squamous epithelium in five
      cases, simple cuboidal epithelium in five cases, and two kinds of above mentioned
      epithelia in eight cases. Goblet cells were present in 23 cases. Surgical
      excision was performed via the labiogingival groove approach for all patients.
      The duration of follow-up ranged from 6 months to 10 years. No postoperative
      recurrences were found. CONCLUSION: The abnormal development of nasolacrimal duct
      systems may take an important role in the pathogenesis of nasal vestibular cyst.
      According to this, we considered the total excision via the sublabial approach is
      more reasonable surgery than endoscopic marsupialization, but it is need further
      observation.

PMID- 17438852
TI  - [Erythromycin effects on apoptosis of epithelial cell in nasal polyps].
AB  - OBJECTIVE: To study the effect of erythromycin on apoptosis in epithelial cell
      and investigate the significance of epithelial cell apoptosis in nasal polyps
      forming. METHOD: Epithelial cell collected from thirty nasal polyps and six
      inferior turbinates were cultured in Dulbecco Eagle and Ham F12 (1:1) and divided
      into two groups, one cultured with Erythromycin(Erythromycin group), another
      cultured without Erythromycin (control group). Apoptosis was detected by terminal
      deoxynucleotidyl transferase mediated dUTP nick end labeling. RESULT: The AI
      (apoptosis index) of epithelial cell in nasal polyps after cultured for 1,3,5
      days with erythromycin were respectively (33.23 +/- 6.50)%, (38.21 +/- 7.22)% and
      (52.63 +/- 7.86)%. The AI of epithelial cell in inferior turbinates were
      respectively (31.02 +/- 5.60)%, (32.13 +/- 7.15)% and (39.64 +/- 7.48)%. There
      were significant difference between two groups at 5 day after culture (P < 0.05).
      CONCLUSION: Erythromycin promoted apoptosis of epithelial cell in nasal polyps.

PMID- 17438853
TI  - [GJB6 gene mutation analysis in Chinese nonsyndromic deaf population].
AB  - OBJECTIVE: To investigate the contribution of GJB6 gene (encoding connexin 30)
      mutation in Chinese population with sporadic non-syndromic hearing impairment.
      METHOD: Three hundred and seventy-two nonsyndromic hearing impairment patients
      and 182 normal controls were first tested for GJB6 del(GJB6 > D13S1830) using
      specific PCR primers. Then PCR was performed with a pair of primer flanking the
      whole coding sequence of GJB6 gene. Sequencing of GJB6 whole coding sequence PCR
      products was subsequently applied in all subjects with hearing loss and normal
      controls. RESULT: None of the patients and normal controls carried GJB6 del (GJB6
      > D13S1830). Two single base pair changes were detected , one in the patient
      group and the other in the control group. The mutation found in the patient group
      was not detected in the control subjects. CONCLUSION: Mutation of GJB6 gene is
      not frequent in Chinese non-syndromic hearing-loss population. Screening for GJB6
      gene can be ranked as unconventional deaf gene test in China temporarily.

PMID- 17438854
TI  - [Three dimensional reconstruction study of multi-slice helical CT imaging on
      optic canal area].
AB  - OBJECTIVE: To investigate the accuracy and clinical application of multi-slice
      spiral CT imaging on optic canal area. METHOD: Forty intact specimens of human
      corpse head were tested with three dimensional reconstruction of multi-slice
      spiral CT imaging. The results of radiology and anatomy were compared on adjacent
      structures of optic canal interior wall and its developmental relationship with
      sphenoid sinus. RESULT: (1) The high spatial resolution of integrity could be
      obtained with dimensional processing technique. The anatomical structure of optic
      canal and its surrounding area could be demonstrated clearly. (2) With the
      technique of virtual endoscopy, the interior reconstruction of optic canal could
      demonstrate the inner topography of optic canal, the reconstruction image of
      which was identical to that of the control subjects. (3) There was no significant
      difference between the data of multi-slice spiral CT imaging and that of anatomy
      (P > 0.05). CONCLUSION: Associated application of dimensional processing
      technique and virtual endoscopy, not only can the subtle structures of optic
      canal be demonstrated and measured, but also the detailed information on spatial
      relationships of optic canal area can be provided for operation.

PMID- 17438855
TI  - [The morphological study of eroded auditory ossicles by cholesteatoma].
AB  - OBJECTIVE: To observe the morphology of eroded auditory ossicles obtained in
      middle ear surgery for cholesteatoma and to investigate the mechanism of bone
      erosion in cholesteatoma. METHOD: The morphology of eroded auditory ossicles in 8
      cholesteatoma cases and 2 normal cases were observed with light microscopy. The
      ultrastructure of eroded auditory ossicles in 5 cholesteatoma cases and the
      ultrastructure of control bones in external ear canal of 2 cases were observed
      and compared with transmission electron microscopy. RESULT: Osteomyelitis and
      multinucleate osteoclasts with ruffled borders were observed in the eroded
      auditory ossicles of cholesteatoma. Intramembranous and endochondral ossification
      were both observed. The obvious bone destruction and remodeling were observed
      consistently. CONCLUSION: Osteoclasts and Osteomyelitis are both responsible for
      bone destruction in cholesteatoma. Intramembranous and endochondral ossification
      may co-participate in bone remodeling. Osteogenesis is also a basic pathologic
      phenomena in cholesteatoma. The obvious bone destruction and remodeling can
      coexist in cholesteatoma cases.

PMID- 17438856
TI  - [Clinical analysis of otitis media with effusion in adults and children].
AB  - OBJECTIVE: To explore the different and common features between adults and
      children with otitis media with effusion (OME) on course of disease, clinical
      characteristics and audiometric changes. METHOD: Pure tone audiometry,
      tympanogram and clinical information were analyzed and compared between 34 cases
      of adults and 42 cases of children with OME. RESULT: The course of disease was
      relatively short in children. The adenoid vegetation inflammation was more
      frequently found in children, while the OME occurred more often in adults. The
      air conduction and bone conduction threshold increased both in children and
      adults, particularly at high frequencies of 2 and 4 kHz. The bone conduction
      threshold at 4 kHz in adults was significantly higher than that in children (P <
      0.05). In the cases with C type tympanogram, the negative pressure in adults was
      even lower than that in children (P < 0.05). CONCLUSION: The OME in children is
      often relatively shorter in course of disease, which is mainly caused by adenoid
      vegetation. Sensorineural deafness can occur both in children and adults,
      especially at high frequencies. OME in children is less severe, however, it may
      lead to negative effects in learning and cognition, which should be diagnosed and
      managed in time.

PMID- 17438857
TI  - [Diagnosis and treatment of congenital abnormality in external and middle ear].
AB  - OBJECTIVE: To investigate the clinical characters, methods of evaluation before
      surgery and effects of treatment of congenital abnormality in external and middle
      ear. METHOD: The data of 21 cases (22 ears) with congenital abnormalities in
      external and middle ear who received operation in ENT Department of the First
      Affiliated Hospital of Zhengzhou University during 5 years from June 2000 to June
      2005 were analyzed. RESULT: Malformations of middle ear were presented in all
      cases. These mainly consisted of small tympanic cavities in 16 ears (72.7%),
      ossicular chain anomalies in 20 ears (90.9%) and facial nerve abnormalities in 8
      ears (36.4%). The hearing improvement was observed in 15 ears (68.2%) after
      surgery, of which 9 ears had hearing improvement greater than 30 dB. Long term
      (0.5 to approximately 5 years) follow-up demonstrated that the hearing in 17 ears
      were kept unchanged after surgery. The postoperative complications were external
      auditory canal stenosis in 4 ears and lateralization of the tympanic membrane in
      2 ears. CONCLUSION: Careful evaluation of the hearing and CT of congenital
      abnormalities of external and middle ear before operation are important.
      Maintenance of width of the external acoustic meatus and prevention of infection
      are crucial in the treatment of congenital abnormalities of external and middle
      ear.

PMID- 17438858
TI  - [Normative data of disyllabic Mandarin speech test materials for normally hearing
      people].
AB  - OBJECTIVE: To analyze the reliability of disyllabic Mandarin speech test
      materials (MSTM) which had previously been evaluated the equivalence of
      difficulty, and to establish the performance-intensity function (P-I function)
      for people with normal hearing. METHOD: Thirty-five subjects (the age-range 18-25
      years) with normal hearing who speak Mandarin well in their daily lives were
      enrolled in this study. Five of them participated the pilot study, which aimed to
      identify a presentation level for the formal test. The other thirty subjects
      participated in the formal speech perception test. The results were analyzed
      statistically using SPSS 11.0 software. Nine lists of the Mandarin disyllabic
      materials with equal difficulty were utilized. RESULT: P-I function was y = 
      200.9 + 13.4x - 0.14x2. The sound pressure level of speech corresponding to a 50%
      recognition score was 26.4 dB SPL, or 6.4 dB HL. CONCLUSION: This study has
      established the P-I function of the Mandarin disyllabic materials with equal
      difficulty, which provides the normative data for identifying the normal hearing
      in a clinical setting.

PMID- 17438859
TI  - [The application of spiral CT in diagnosing the otitis media with cholesteatoma].
AB  - OBJECTIVE: To discuss the application of spiral CT imaging of temporal bone in
      diagnosing the chronic otitis media with cholesteatoma. METHOD: The clinical data
      and spiral CT manifestation of 104 cases of chronic otitis media with
      cholesteatoma were retrospectively analyzed. All the diagnoses were confirmed by
      operation and pathology. RESULT: Spiral CT imaging could accurately show the
      signs of soft-tissue occupancy and bony-erosion of by cholesteatoma in middle ear
      which originated from various sites and of various sizes. Comparing the CT
      imaging before surgery and the findings during the operation, the consistency in
      bone erosion was 89.1%, in soft-tissue occupancy was 94.4% and in invasion of
      ossicle chain was 89.3%. CONCLUSION: Spiral CT imaging plays an important role in
      diagnosing cholesteatoma and especially the bony-erosion and the soft-tissue
      occupancy, which can provide crucial information for the surgery.

PMID- 17438860
TI  - [Facial nerve root combing scraping for hemifacial spasm].
AB  - OBJECTIVE: To explore the effective intracranial surgical method for hemifacial
      spasm which can be operated more safely and easily. METHOD: Twenty-five cases of
      hemifacial spasm underwent intracranial facial nerve root combing scraping by
      improved retrosigmoid approach. The compressing vessels were found in 10 cases
      and could be removed easily. Both microvascular decompression and facial nerve
      root combing scraping were performed to reduce recurrence. The other cases with
      perforating artery or without any compressing vessels underwent the facial nerve
      root combing scraping and cutting off partially for about 1/6 to approximately
      1/5 neural fibers. RESULT: Hemifacial spasms were obliterated in 22 cases (88%)
      after operation, obviously relieved in 2 cases (8%), invalid in 1 case (4%).
      Varied facial nerve paralysis was observed in 25 patients, but no hearing
      disturbance and other serious complication occurred. Follow-up for 2 to
      approximately 8 years showed there were recurrences in 2 cases (8%) and the
      facial nerve paralysis of 25 cases recovered in 1 to approximately 6 months after
      operation. CONCLUSION: The facial nerve root combing scraping is an effective and
      safe microsurgical procedure which has wide-ranged indication and less
      complication. It is very important to select suitable treatment for the patient
      individually during the operation to improve the efficacy and lower the risk.

PMID- 17438861
TI  - [The primary culture of rats cochlear sensory epithelial cell and the
      significance of expression of hair cell characteristic markers of CSEC].
AB  - OBJECTIVE: To further investigate the mechanisms of hair cell generation or
      regeneration, the primary culture systems of cochlear sensory epithelial cell
      (CSEC) of rats were established. METHOD: Cochlear sensory epithelial (containing
      the organ of Corti) of postnatal day 1 (P1) rats was isolated by mechanical
      dissociation. The explants were grown on sterilized disposable plastic
      dishes,cultured in Dulbecco modified Eagle medium(DMEM), and observed daily by
      inverted microscopy. The culture medium was changed twice a week. The pure CSEC
      was harvested by the limiting dilution method. CSEC was identified by
      immunocytochemical method with cytokeratin 18, vimentin, Brn3. a, Calretinin,
      BrdU and ultrastructural examination with transmission electron microscopy. The
      markers of epithelial cell and the markers of hair cell were used to identify the
      origin and character of CSEC. CSEC mitotic division was detected by BrdU staining
      of nuclear DNA. RESULT: The fresh explants were light yellow. The morphology of
      CSEC couldn't be seen clearly under the inverted microscope because of the
      complex structures of cochlear sensory epithelial. CSEC grew out of the explants
      usually at 2nd culture day. Fibroblast like cells (FLC) around the CSEC grew
      faster than CSEC, but could easily be excluded. Pure CSEC may grow into monolayer
      with 'cobblestone-like' appearance and show a large, flat, polygonal epithelial
      morphotype with big, round nuclei. Some cells showed 'Dome' formation, probably
      due to fluid collection underneath the cell monolayer. The culture CSEC
      coexpressed cytokeratin 18 and vimentin has rich microvilli and complex tight
      junction,which indicated the epithelial origination of CSEC. Coexpressed of the
      Brn3. a and Calretinin of the hair cell characteristic markers suggested the
      culture cell may represent rat progenitor hair cell. BrdU staining showed CSEC
      produced new hair cell-like cell (progenitor hair cell) by the mitotic division.
      CONCLUSION: The primary culture systems of cochlear sensory epithelial cell of
      rats were successfully established in vitro. CSEC coexpressed the characteristic
      markers of the immature hair cell,which identified the culture cell may represent
      progenitor cell of rats hair cell. It may be a suitable model for in-depth
      investigation the molecular mechanisms of hair cell generation or regeneration.

PMID- 17438862
TI  - Validation of HPLC method for determination of atorvastatin in tablets and for
      monitoring stability in solid phase.
AB  - A rapid high performance liquid chromatographic method was developed and
      validated for determination of atorvastatin in pharmaceutical dosage forms, and
      for evaluation of its stability in the solid phase. Separation of atorvastatin
      was successfully achieved on a C-18 column utilizing water--acetonitrile at the
      volumetric ratio of 48:52, adjusted to pH 2.0 with 80% ortho-phosphoric acid. The
      detection wavelength was 245 nm. The method was validated and the response was
      found to be linear in the drug concentration range of 0.04 mg/mL - 0.4 mg/mL. The
      mean values +/- RSD of the slope and the correlation coefficient were 8.192 +/-
      0.260 and 0.999, respectively. The RSD values for intra- and interday precision
      were < 1.00% and 0.90%, respectively. The degradation kinetic of atorvastatin at
      363 K in a relative humidity of 76.4% was observed to be autocatalytic first
      order reaction. The kinetic parameters were as follows: k (where k represents the
      velocity constant; s(-1)) = (1.42 +/- 0.19) 10(-6); t(0.5) (where t(0.5)
      represents the time needed for a 50% decay of atorvastatin; days) = 32.82 +/-
      0.9; t(0.1) (where t(0.1) represents the time needed for a 10% decay of
      atorvastatin; days) = 13.86 +/- 0.8.

PMID- 17438863
TI  - Thermal stability of 1,4-dihydropyridine derivatives in solid state.
AB  - The effect of temperature and air humidity on the stability of 7 derivatives of
      1,4-dihydropyridine (nifedipine, nisoldipine, nitrendipine, nimodipine,
      nicardipine, felodipine and amlodipine) in solid state has been studied by
      accelerated testing. Quantitative analysis of the compounds studied was made by
      UV spectrophotometry, identification of the thermodegradation products and
      reference to the standard were made by thin layer chromatography (TLC), UV
      spectra and the reaction with KMnO4. Thermodegradation of the derivatives studied
      was found not to occur in dry air, whereas at air humidity it occurred according
      to the first order reaction at a similar rate for all derivatives. The main
      product of thermodegradation of the derivatives with the nitro substituent was a
      nitrozoderivative formed as a result of dihydropyridine ring aromatisation
      accompanied by water molecule elimination.

PMID- 17438864
TI  - Synthesis of oxiran-2-ylmethyl and oxiran-2-ylmethoxy derivatives of some 4
      azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-diones as potential beta-adrenolytics.
AB  - A series of aminoalkanol derivatives of 10-(diphenylmethylene)-4
      azatricyclo[5.2.1.0(2.6)]dec-8-ene-3,5-dione and 4-hydroxy-4
      azatricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione have been prepared. The
      pharmacological profile of selected compounds was evaluated for their affinities
      at beta-adrenoceptors. The investigated compounds exhibit modest affinity for
      these receptors.

PMID- 17438865
TI  - Synthesis and antimicrobial activity of 3-(4'-hydroxy-3'-methylphenyl)-5
      [(substuted) phenyl]-4,5-dihydro-1H-1-pyrazolyl-4-pyridylmethanone derivatives.
AB  - A series of 3-(4'-hydroxy-3'-methylphenyl)-5-[(substituted) phenyl]-4,5-dihydro
      1H-1-pyrazolyl-4-pyridylmethanone derivatives were synthesized by the reaction
      between isoniazid (INH) and various chalcones and were tested for their
      antimicrobial activity in vitro against Staphylococcus aureus 209p, Escherichia
      coli ESS 2231, Aspergillus fumigatus, Candida albicans, Candida albicans ATCC
      10231, Candida krusei GO3 and Candida glabrata HO5. Among the synthesized
      compounds, all the compounds possess the significant antibacterial activity.
      Compounds I(III) and I(x), i.e. 3-(4'-hydroxy-3'-methylphenyl)-5-(4"
      dimethylaminophenyl)-4,5-dihydro-1H-1-pyrazolyl-4-pyridyl methanone and 3-(4'
      hydroxy-3'-methylphenyl)-5-(2",6"-dichlorophenyl)-4,5-dihydro-1H-1-pyrazolyl-4
      pyridylmethanone were found to be the most active agents against used bacterial
      and fungal strains with minimum inhibitory concentration of less than 0.5
      microg/mL and were equally active as standard drugs Ofloxacin and Fluconazole.

PMID- 17438866
TI  - Analysis of aqueous extract of Inonotus obliquus.
AB  - Water-soluble melanin complexes were extracted with hot water from Inonotus
      obliquus fungus. They were characterized before and after reaction with diluted
      hydrochloric acid. The organic components as products of degradation of melanin
      complexes were separated by column chromatography and analyzed by GC-MS method.

PMID- 17438867
TI  - Evaluation of purity of certain pediatric preparations of plant origin and its
      significance for the safety of pharmacotherapy microbiological contamination of
      pediatric preparations of plant origin.
AB  - Microorganisms inhabiting medicinal plants belong to either saprophytic or
      pathogenic flora. Even those microorganisms which are characterized by low
      pathogenicity, under favorable conditions may infect people who have had contact
      with them. Compound tea bags contain increased levels of bacteria in view of
      pharmacopoeic norms. Single plant tea bags contain less bacteria and granulated
      teas have the lowest content. On the other hand, the latter reveal higher level
      of fungal contamination. Processing of herbs, including brewing decreases the
      amount of microorganisms in herbal products.

PMID- 17438868
TI  - Influence of additives and storage temperature on physicochemical and
      microbiological properties of eye drops containing ceftazidime.
AB  - The purpose of the studies was to examine the influence of additives and the
      storage temperature on the physicochemical properties of the eye drops containing
      ceftazidime and on the antimicrobial activity of ceftazidime in the eye drops
      stored for 30 days at the temperature of 4 degrees C and 2 degrees C. The eye
      drops were 1% sterile aqueous solutions of Biotum (Ceftazidimum) in citrate
      buffer of pH 6.18-6.30, which were preserved with 0.002% thiomersal or 0.001%
      phenylmercuric borate mixed with 0.4% beta-phenylethyl alcohol. The viscosity of
      the eye drops was increased with polyvinyl alcohol. The pharmaceutical
      compatibility test showed the pharmaceutical interaction of 1% solution of Biotum
      with thiomersal at the concentration higher than 0.003%, with 0.01% chlorhexidine
      diacetate and with 15% polyvinylpyrrolidone. As the criteria of the qualitative
      assessment of both freshly prepared eye drops and those stored at the temperature
      of 4 degrees C and 20 degrees C, the following analyses were considered:
      organoleptic analysis (color, clarity, and smell), sterility, pH, osmotic
      pressure and viscosity. The antimicrobial activity of ceftazidime and the
      preservation efficiency of thiomersal and phenylmercuric borate in the eye drops
      were determined using methods of the Polish Pharmacopoeia VI (PPh VI). The
      antimicrobial activity of ceftazidime in the drops was especially influenced by
      their storage temperature. After 30 days of storage at the temperature of 4
      degrees C, there was no decrease of antimicrobial activity of ceftazidime
      detected in the eye drops. However, when the eye drops were stored at the
      temperature of 20 degrees C, the decrease of antimicrobial activity of
      ceftazidime was observed already after 14 days. After 30 days of storage both at
      the temperature of 4 degrees C and 20 degrees C, neither pH nor viscosity of the
      eye drops changed; however, the osmotic pressure was decreased.

PMID- 17438869
TI  - In vitro investigation of sodium diclofenac adsorption on sucralfate.
AB  - Adsorption of sodium diclofenac was investigated in the presence of sucralfate--a
      cytoprotective agent preventing gastropathy, adverse effect of diclofenac.
      Evaluation of adsorption was performed by means of a static method in vitro
      taking into account pH of the environment, temperature, concentration of the
      investigated agents and the form of sucralfate. Findings obtained prove that
      sodium diclofenac is adsorbed on sucralfate in all investigated pH ranges and the
      capability of sucralfate binding depends on its form, temperature and
      environmental pH. The highest binding was observed at pH 5.0 in the presence of
      sucralfate, which at this pH has the form of a suspension, while the lowest--at
      pH 1.5 in the presence of sucralfate in the form of paste. Low values of
      adsorption temperature of diclofenac as well as the relationship between the
      level of its adsorption and environmental pH are the dominating factors pointing
      to the physical and exothermic adsorption.

PMID- 17438870
TI  - Preparation and evaluation of modified release ibuprofen microspheres with
      acrylic polymers (Eudragit) by quasi-emulsion solvent diffusion method: effect of
      variables.
AB  - The aim of this study was to prepare and evaluate microspheres containing
      ibuprofen. Microspheres were prepared by modified quasi-emulsion solvent
      diffusion method. The influence of formulation factors (drug-polymer ratio,
      volumes of solvent, polyvinyl alcohol concentration and type of polymer) on the
      morphology, particle size distribution, drug loading capacity, micromeritical
      properties and the in vitro release characteristics of the microspheres were
      investigated. Physical characterizations of ibuprofen microspheres were also
      carried out using scanning electron microscopy, X-ray diffractometry and IR
      spectrophotometry. It was found that the yield of preparation was dependent on
      the initial temperature gradient between the emulsion phases. When there was an
      initial difference of temperature between the aqueous phase and dispersed
      emulsion phases, yield of preparation was increased distinctly. The drug loading
      capacities were very high for all formulations of the microspheres which were
      obtained. Mean particle size changed by changing the drug-polymer ratio, volumes
      of solvent or polyvinyl alcohol concentration. The flow properties were much
      improved over those of the original crystals. In vitro dissolution results showed
      that the release rate of ibuprofen was modified in all formulations. Although
      ibuprofen release rates from Eudragit RS microspheres were very slow, they were
      fast from Eudragit RL microspheres. These results observed that if Eudragit RS
      and Eudragit RL are used in combination, optimum release profiles may be
      obtained.

PMID- 17438871
TI  - Effect of penetration enhancers on skin permeation of trazodone hydrochloride
      from matrix type transdermal formulation through mouse and human cadaver
      epidermis.
AB  - A transdermal dosage form of trazodone hydrochloride (TZN) may be useful in the
      treatment of moderate to severe depression in schizophrenic patients by providing
      prolonged duration of action. It will also improve patient compliance and
      bioavailability. Controlled input of TZN would attenuate fluctuating plasma level
      of TZN resulting from oral therapy. The aim of the current investigation was to
      evaluate its flux and the effects of various penetration enhancers, viz.,
      isopropyl myristate (IPM), isopropyl palmitate (IPP), butanol and octanol on
      transdermal permeation from matrix-based formulations through the skin. The
      enhancing effect on the permeation of TZN was determined using the mouse and
      human cadaver epidermis. In vitro permeation data were collected at 37 degrees C
      using Keshary-Chien diffusion cells. The skin permeation was then evaluated by
      measuring the steady state permeation flux of TZN, enhancement ratio and the
      diffusion parameter. The highest enhancing effect was obtained with IPM followed
      by butanol, octanol and IPP. In general, higher fluxes were observed through
      mouse epidermis as compared with the human cadaver epidermis. The skin retention
      of TZN for both the species in the presence of different enhancers was nearly 3
      times higher than for the control formulation. Based on the observed results, a
      transdermal patch of about 70 cm2 consisting of 10 % IPM should be able to attain
      and maintain therapeutic plasma concentration of TZN at 0.75 mg/mL over a period
      of 24 h.

PMID- 17438872
TI  - The influence of staphylococcin T (StT) on the mouse fibroblasts (3T3) viability,
      an in vitro experiment.
AB  - Staphylococcin T (StT) is a bacteriocin, which can serve as an antibiotic. The
      influence of StT on the mammalian cells viability should be examined before its
      possible applications. The aim of this work was to study the influence of StT on
      mouse fibroblasts viability in vitro. StT was delivered as a deposit in agar. 3T3
      fibroblasts were used in viability tests. Cells were incubated with StT for 24
      and 48 h. In the first controls, cells grew without the agar block, in the second
      controls, the agar block contained no StT. Trypan blue exclusion test was
      performed. Growth inhibition of sensitive strain SAU-209P was observed after 24 h
      incubation with cell culture medium containing StT. Antimicrobial activity of StT
      in culture medium was confirmed even after 2 months. The viability of 3T3 cells
      in the second control group was 50% lower than in the first and 25% higher than
      in StT treated group during the first day. It was noticed mechanical damage of
      growing cells caused by agar blocks. The number of cells cultured with StT was
      similar to that of second control group after 2 days. There were no changes in
      morphology of cells in all groups. It follows that StT had unimportant influence
      on the fibroblasts (3T3) viability in culture. StT may be considered for future
      animal trails.

PMID- 17438873
TI  - Effect of Vita Glucan on some antioxidant parameters of the human blood. In vitro
      study.
AB  - Recently, beta-glucan has been postulated to modulate antioxidant enzyme activity
      (superoxide dismutase-SOD) as well as to inhibit lipid peroxidation in studies
      concerning rats or rabbits. There are very few reports on antioxidant effect of
      beta-glucan in the human blood. The study was aimed to estimate influence of Vita
      Glucan (VG) on SOD and catalase (CAT) activities as well as on total antioxidant
      power measured as ferric reducing activity and ascorbate concentration (FRASC) in
      the human blood in vitro. SOD activities were measured according to Fridovich's
      method, CAT activity by Aebi's and FRASC value by Benzi's one. Results of this
      study have shown that Vita Glucan at concentrations 42.5, 85, 170, and 340 mg x
      100 mL(-1) increased markedly activities of antioxidant enzymes and FRASC values
      in human red blood cells hemolysates.

PMID- 17438874
TI  - [Primum-non nocere! Do we abandon liver biopsy?].

PMID- 17438875
TI  - Transient elastography--an alternative to liver biopsy in patients with chronic
      hepatitis C?
AB  - Liver fibrosis is the main determinant of clinical outcomes of chronic hepatitis
      C. Liver biopsy is still considered the gold-standard for assessing liver
      fibrosis. However, liver biopsy is an invasive procedure associated with
      morbidity and mortality and has several limitations. Moreover, liver biopsy is
      not well accepted by the patients, especially when repeated examinations are
      needed, and its accuracy in assessing fibrosis is questionable due to sampling
      errors, intraobserver and interobserver discrepancies. Therefore, over the last
      years there has been an increasing interest and desire for non-invasive tests to
      assess the stage of liver fibrosis in patients with chronic hepatitis C. There
      are three main groups of non-invasive methodologies for the assessment of liver
      fibrosis: serum markers, imaging techniques, and transient elastrography. This
      review summarizes current information on transient elastography used for non
      invasive diagnosis of liver fibrosis in patients with chronic hepatitis C.

PMID- 17438876
TI  - [Obesity in children: new controversies and present prevention measures].
AB  - The authors realise a synthesis on classical data and recent pathogenic
      explanations in childhood obesity. The obesity is a nutritional disorder of great
      interest nowadays and surpasses the incidence of the major problem of pediatrics
      until now--the malnutrition. There is documented data concerning the global
      incidence of obesity which is continuously growing when it comes to children.
      That is why the prophylaxis must become a priority by using measures in the first
      period of life (natural feeding, the need of late diversification, the avoidance
      of hyperproteic diets). The recent pathogenic data and the long term populational
      studies change the old conceptions regarding the risk of some categories of
      children. Thus mother's malnutrition, the low birth weight, children that
      followed hyperproteic diets paradoxically represent categories of risk for
      obesity. A recent recorded phenomenon, which amplifies the risk for obesity is
      the early adiposity rebound which is recorded nowadays even for ages lower than
      five years. There are described the hormonal mechanisms involved in appetite and
      satiety up to the receptor level: leptin, ghrelin, adiponectin, endocannabinoid
      receptors. There are pointed out all the long term risk elements (high birth
      weight, low birth weight, the pregnant woman's nutrition) and the modern medical
      treatments for obesity.

PMID- 17438877
TI  - [Vasospastic angina].
AB  - Vasospastic angina is associated with ventricular arrhythmias, acute myocardial
      infarction and sudden arrhythmic death. The main ischemic mechanism in
      vasospastic angina is coronary spasm. Because the demonstration of spontaneous
      coronary spasm is difficult, a number of methods which can provoke spasm in
      susceptible patients were imagined. The most used clinical methods of diagnostic
      provocation testing were analyzed.

PMID- 17438878
TI  - [Erythema toxicum neonatorum].
AB  - (ETN) is a benign, self limited, asymptomatic skin condition, that only occurs
      during the neonatal period. This clinical entity is caractherized by small,
      sterile, erythematous papules, vesicles, and occasionally pustules, appearing on
      the trunk, extremities, and the face. The lesions are transitory, appear after 1
      2 day of life, and regres after 5-14 days. ETN occurs in 30-50% of full-term
      infants, and just in 5% of preterm infants, with no significant differences based
      on race or sex. The ethiology or pathophysiology of ETN are uncertain, but the
      presence of the eosinophilic infiltrate in the lesions of erythema suggests an
      allergic ethiology, even no allergens have been identified. The treatment is not
      required, and the prognosis is excellent with spontaneous resolution.

PMID- 17438879
TI  - [Malnutrition and complex nutritional therapy in cystic fibrosis].
AB  - Good nutrition is essential for normal growth and development. Cystic fibrosis
      (CF) is commonly associated with energy deficiency in children. Malnutrition is a
      very frequent complication and contributes significantly toward morbidity in CF.
      Although malnutrition due to pancreatic enzyme insufficiency is correctable, the
      majority of CF patients are underweight and have short stature. During the last
      few decades, improved treatment measures and nutritional support in CF have
      increased survival and quality of life in these patients. Patients with CF must
      receive a hypercaloric and hyper-proteic diet, with a high fat content, a normal
      quantity of carbohydrates and with pancreatic and liposoluble vitamin supplements
      in case of pancreatic insufficiency.

PMID- 17438880
TI  - [Epidemiology, risk factors and morphopathology of choledocholithiasis].
AB  - Gallstones are a major cause of morbidity worldwide, and cholecystectomies are
      the most common elective abdominal operations performed in the United States. Our
      understanding of the pathogenesis and treatment of gallstones has changed
      dramatically over the past decade. This article reviews the current knowledge of
      the epidemiology, etiology and morphopathology of common bile duct stones. Large
      studies in which sonographic screening or necropsy data were used to estimate the
      prevalence of gallstone disease in different populations and to define risk
      factors, amenable to prevention. Within a population, gallstones occur
      sporadically but not randomly; specific risk factors have been identified that
      predict stone formation. Based in large part on composition, gallstones are
      categorized as cholesterol, black pigment, or brown pigment stones, with each
      category having a unique epidemiology and characteristic risk factors.

PMID- 17438881
TI  - [Endothelial dysfunction assessment using vascular ultrasound in heart failure
      patients].
AB  - Endothelial dysfunction is an important factor leading to atherosclerosis,
      hypertension and heart failure. Flow mediated dilatation (endothelium dependent
      function) can be evaluated by vascular ultrasound. We investigated 71 heart
      failure patients (36 men-50.7%, 35 women-49.3%). The evaluation methods were:
      electrocardiogram, vascular ultrasound, echocardiography, chest X ray,
      hematological and biochemical tests. The statistical correlations were performed
      between clinical data, morphologic and hemodynamic parameters. Our results showed
      that endothelial dysfunction was present in all heart failure patients but it did
      not correlate with hemodynamic parameters. Elastic arterial parameters variation
      correlated with heart failure severity and flow mediated vasodilation.

PMID- 17438882
TI  - [Conventional ultrasound in the diagnosis of bile duct calculi].
AB  - Transabdominal ultrasound (US) is one of the most useful methods in the diagnosis
      of biliary stones. AIM OF THE STUDY: To appreciate the value of US in the
      diagnosis of bile duct stones. MATERIAL AND METHOD: 989 patients, explored in the
      Institute of Gastroenterology and Hepatology Iasi by US compared with ERCP, MRCP,
      operative diagnosis and the final diagnostic. RESULTS: The sensitivity of US in
      the detection of bile duct stones was 78.39% and specificity was 72.22% in the
      first group of 650 patients, and bile duct stones were identified in 139 cases of
      339 of the second group where US could not identify the cause of bile duct
      dilatations. DISCUSSION: The results were comparable with the most recent studies
      in the literature. CONCLUSION: US is an efficient method for the diagnosis of
      bile duct stones in many cases and remains the first step in the diagnosis.

PMID- 17438883
TI  - Allergic reactions to antithyroid drugs are associated with autoimmunity a
      retrospective case-control study.
AB  - Thiamazole is the most used antithyroid drug for thyrotoxicosis in Basedow
      Graves' (BG) (autoimmune) disease and in toxic multinodular goitre (TMG) (non
      autoimmune). This study aims to find whether allergic reactions to thiamazole
      occur more frequently during the treatment of BG than of TMG. METHOD:
      Retrospective study, of 128 patients newly diagnosed and treated for
      thyrotoxicosis in the first 6 months of 2006, in the Endocrinology Department of
      "Elias" Hospital, Bucharest. Cases were all patients treated with thiamazole who
      developed allergic reactions. Controls were all patients treated with thiamazole
      without allergic reactions. Risk factor was considered to be the presence of BG.
      RESULTS: Cases group consisted of 6 patients. All 6 started treatment with
      thiamazole for BG, and developed allergic reactions after 2-4 weeks of treatment.
      When thiamazole was withdrawn, allergic symptoms ceased under antihistamines and
      steroids. In order to control the thyrotoxicosis, antihistamines and oral
      steroids was administered, together with thiamazole in slow increasing doses.
      After about 4 weeks under this combination, a tolerance to thiamazole seems to
      appear. Control group consisted of 122 patients who started thiamazole: 66 for BG
      and 56 for TMG (without allergic reactions). CONCLUSION: Allergy to thiamazole
      was significantly associated with the autoimmune BG, and not with TMG (p = 0.03,
      OR = 11.04). None of the patients with TMG developed allergic reactions to the
      drug. Tolerance to this drug may occur.

PMID- 17438884
TI  - [Postmenopausal osteoporosis. Digital Rx radiogrammetry in the diagnosis and
      follow-up of treatment with alfacalcidol].
AB  - Postmenopausal osteoporosis is characterised by an increased resorption of
      trabecular bone, a consequence of estrogen deficit. Changes in vitamin D
      metabolism are also an important contributors to the development of osteoporosis
      in postmenopausal women. Vitamin D and its active metabolites (Alfacalcidol,
      Calcitriol) perform important functions in regulation of the calcium balance and
      the bone metabolism. Aim of our study was to determine the efficacy of
      Alfacalcidol (Alpha D3) in reducing the loss of bone mass. 391 postmenopausal
      women with osteopenia and 165 postmenopausal women with osteoporosis were treated
      24 months with Alfacalcidol. The bone mineral density (BMD) was measured by
      Digital Rx Radiogrammetry (DXR). In osteopenic women treated with 0.5 mg
      Alfacalcidol, bone mineral density increased after 12 and 24 months with 3.4% and
      2.3%. In osteoporotic women the increase of BMD was 1.8% and 2.4% after 12 and
      respectively 24 months. On the control group BMD decreased with 3.4% after 24
      months. In our study Alfacalcidol confirmed the abolishment of the loss of bone
      mass.

PMID- 17438885
TI  - [Oxidative stress and immune response in eumenorrheic underweight patients].
AB  - Malnutrition is known to induce a state of immunodeficiency and a predisposition
      to death from infectious diseases. During fasting or starvation, it appears that
      oxidative stress is decreased. The goal of our study was to assess the
      interrelation between nutritional factors, oxidative stress and immune response.
      The malondialdehyde (MDA)-marker of lipid peroxidation, white blood cell count,
      differential count and hormonal status (FSH, LH, and cortisol) were followed in
      eumenorrheic underweight patients. MDA was significantly lower and lymphocyte
      count was significantly increased in eumenorrheic underweight patients as
      compared to normal weight patients. Gonadal and adrenal axes were found normal in
      eumenorrheic underweight patients. Body mass index was positively correlated with
      MDA and negatively correlated with lymphocyte count. Low levels of lipid
      peroxidation and non-suppressed immune function in underweight patients may be
      explained by an increased sensitivity to leptin but further studies are
      requested.

PMID- 17438886
TI  - [Clinical and epidemiologic aspects of attention deficit hyperactivity syndrome
      (ADHD) in ambulatory practice].
AB  - The purpose of the study was to determine the prevalence and to describe the
      clinical presentations of Attention Deficit Hyperkinetic Syndrome in the
      pediatric patients of the Outpatient Specialty Clinic of the "Sf. Spiridon"
      University Hospital of Iasi (a pediatric neuro-psychiatry practice and a general
      pediatric practice). The studied group consisted of 51 children and adolescents
      ages 2 years 6 month-18 years of age (urban environment 34 children--66%, rural
      environment 17 children--34% ; male gender 36 children--70%, female gender 15
      children--30%). The pediatric patients represented a prevalence of 1.9% of the
      Attention Deficit Hyperkinetic Syndrome having the main features: motor and
      psychological instability, lack of attention, negativism, impulsivity, and social
      and school integration difficulties. The existence in 40% of cases of family
      problems (couple pathology, parents with psychiatric disorders, alcoholism, etc)
      proves the importance of the family patterns description in the apparition and
      evolution of Attention Deficit Hyperkinetic Syndrome. The study performed
      underlines the existence of the Attention Deficit Hyperkinetic Syndrome, the
      necessity of multi-disciplinary intervention with the purpose of precise and on
      time diagnosis of this syndrome, to ensure a better integration of these children
      and teenagers in the social and school environment.

PMID- 17438887
TI  - [Varicella-zoster infection--extreme clinical aspects].
AB  - Infections with the varicella-zoster (VZ) virus are a constant of our everyday
      practice. The aim of the present study is that of underlining unusual aspects of
      the infection with the VZ virus--primary infection in adults and herpes zoster in
      children. If varicella, or chickenpox, has been traditionally considered a
      childhood disease, nowadays, an increased number of adults are affected by
      primary infections. On the contrary, more and more children present the secondary
      form of the infection, which appears as herpes zoster, a disease usually
      diagnosed in adults. MATERIAL AND METHODS: We studied the observation papers of
      adult patients with varicella, hospitalized in our clinic during 2004-2005 and we
      analyzed the herpes zoster manifestations in non-HIV children, diagnosed with the
      disease during the same period of time. RESULTS: During 2004-2005, 34 adult
      patients were diagnosed with varicella, while 10 children presented herpes
      zoster. 16 of the adults with varicella were 25-34 years old. One of the children
      with herpes zoster was less than one year old. All the adults with varicella were
      treated with acyclovir; in 14 cases, the therapy was supplemented with
      rifampicin. All the children with herpes zoster came from rural areas. The
      pathology that determined the decrease of general immunity was represented by
      neoplasia (3 cases), malnutrition and rickets (2 cases), associated infectious
      pathologies--bronchopneumonia (3 cases). CONCLUSIONS: Varicella in adults has an
      increased incidence, which is underestimated, in our opinion. Its loud clinical
      manifestations impose the therapy with acyclovir. Herpes zoster in children
      reveals significant subsidiary pathologies and a depressed immune system that
      impose special medical care and many days of hospitalization.

PMID- 17438888
TI  - [The co-infection with hepatitis virus B and D--cases admitted in the infectious
      diseases hospital from Iasi, Romania (2003-2005)].
AB  - Despite the major medical advance, over 350 million people worldwide still have
      chronic infection with hepatitis B virus and HBV-associated liver disease remains
      a major cause of morbidity and mortality. 15-50% of patient VHB infected have
      serological markers for VHD co-infection. We retrospectively studied 252 cases of
      acute hepatitis B (AHB) admitted in our hospital between 2003-2005; 12 of them
      (4.76%) had a co-infection with hepatitis D virus. Most of the patients were
      young males with an urban origin. The route of transmission was unknown in 8/12
      cases. Abdominal pain was more frequent during the onset of the disease than in
      AHB (p < 0.05). A cholestatic pattern was noted in 9 cases. The frequency of
      severe/ fulminant cases was greater then in AHB. The HBsAg was absent in 3
      patients, and the HBV-DNA was present at low levels in 3/12 patients tested. Two
      patients had HBsAg present 6 month later.

PMID- 17438889
TI  - [Etiopathogenical relationship between ENT pathology and tabacco smoke].
AB  - The upper aerodigestive tract is the first compartment of the human body that
      takes contact with the harmful components of the tobacco smoke. The passage of
      the smoke, whether in an active or even passive smoker determines some
      alterations in the ENT area, which is directly exposed to the harmful action of
      the tobacco smoke. In this study we intend to analyze the relations between the
      ENT pathology exemplified at all levels (nasal, laryngeal, ear) and the tobacco
      smoke. Based on some studies, this paper describes the alterations that occur at
      the level of the nasal fossae, oral cavity, larynx and pharynx, and also at the
      level of the ear. The article analyses the relationship between these alterations
      and the determined pathology. Based on the statistic studies, we relate the
      active and passive smoke with the possibility of the development of neoplasia in
      some organs of the ENT area. In conclusion we insist on the necessity that the
      medical publications as well as the mass media to incriminate smoking as the most
      relevant risk factor in the development of cancer in the upper mentioned organs,
      in the twenty first century where tobacco is considered a worldwide epidemic.

PMID- 17438890
TI  - [Bilateral breast cancer (BBC). Considerations on a series of 20 cases].
AB  - The aim of this study was to assess breast cancer incidence, diagnostic
      possibilities in clinical treatable stages and the prognosis in a series of
      breast cancer patients repeatedly treated in the same unit, by the same team.
      Diagnostic difficulties in the early stage of the contralateral cancer constitute
      a proven reality even in our cases. The detection of the second metachronous
      breast tumor was done and evaluated mostly in an more advanced stage than the
      initial tumours. This might be explained by the delayed visit to the doctor. Most
      BBC were lobular carcinoma. Adjuvant therapy--chemotherapy, antiestrogens,
      ovariectomy--do not prevent the appearance of the second tumoral site.

PMID- 17438891
TI  - [The assessment of empiric antibiotherapy in acute secondary peritonitis].
AB  - The adequate use of antibiotics, according to the international guidelines of
      antimicrobial therapy, is, in addition to surgery, an important part of the
      management of intra-abdominal infections. The aim of the study was to assess the
      efficacy of empiric antibiotherapy in acute peritonitis of digestive cause.
      MATERIAL AND METHODS: A retrospective study was carried out on a series of 75
      cases of acute peritonitis, admitted in the IIIrd Surgical Unit, in the period
      2003-2005. Perforated duodenal ulcer was the cause of diffuse peritonitis in 46 %
      of the cases, followed by acute appendicitis (31%) and traumatic perforation of
      the small bowel (11 %). The most frequent bacteria encountered was E. coli (62
      %), while Klebsiella, Enterobacter and Acinetobacter were present in nearly 8% of
      the cases. Ertapenem as single agent was preferred in 36.8% of the patients and
      an association of third generation cephalosporins or aminoglycoside with
      metronidazole in 33.4%. RESULTS: the efficiency of the treatment was assessed in
      regard to clinical (fever) and laboratory (leucocytosis) data, the duration of
      treatment and hospital stay. The outcome was appreciated as good in almost 73% of
      the patients treated with ertapenem, and 52% respectively for combined therapy.
      CONCLUSION: the authors recommend the use of penems as monotherapy in the empiric
      treatment of acute peritonitis following digestive perforation.

PMID- 17438892
TI  - [Gastroduodenal ulcer refractory to conservative treatment].
AB  - This is a 20-year retrospective study on 205 patients in which surgery for
      gastroduodenal ulcer was performed. In 51 one of these patients (24,8%) surgery
      was required by drug therapy failure, cases labeled as drug-resistant ulcers.
      Some causes of drug therapy failure are discussed, failure being also recorded in
      patients who benefited from modem ulcer drugs that proved only partially
      effective. The authors emphasize that surgery can no longer represent a
      therapeutic option, an utter substantiation not only from the surgeon but also
      from the entire team of specialists in various investigation types and
      therapeutics being mandatory.

PMID- 17438893
TI  - [Congenital oropharyngeal tumors in the newborn: problems in team diagnosis and
      treatment].
AB  - There are a great variety of lesions of oral cavity which may require surgical
      intervention in neonatal period. The differential diagnoses include tumors
      (malignant, teratoma, cystic hygroma, lymphangioma, hemangioma), congenital
      epulis, dermoid cysts, ranula. Congenital epulis of the newborn is a rare tumour
      which is usually benign. Epulis is also known as a congenital gingival granular
      cell tumour because of its histological features. Female babies are affected 8-10
      times more often than males. Epulis is located on the maxillary ridge twice as
      often as on the mandible, mostly as single tumours but rarely as multiple
      tumours. The histogenesis of the tumour is unknown. Spontaneous regression of
      congenital epulis has been reported in a few cases. However, surgical excision is
      generally indicated due to interference with feeding or respiration. Recurrence
      of the tumour after surgery has not been reported yet. We report two cases of
      congenital epulis, one in 2 hour female neonate and one in a 7 days male neonate.
      In spite of the rarity of this pathology, the interval between presentation in
      this two cases was ten days. In one case it was an antenatal diagnosis by
      ultrasonography, in the other it was associated a genital anomalies
      (hypospadias). The treatment was surgical excision. The intra- and postoperative
      course was uneventful.

PMID- 17438894
TI  - [Cytologic examination of the axillary lavage fluid obtained during modified
      radical mastectomy].
AB  - The axillary dissection is part of the breast cancer surgical protocol. We have
      cytologically analyzed the axillary lavage fluid obtained during 67 modified
      radical mastectomy. Our results showed good correlation between the node status,
      histological grading and the cytological diagnosis of the axillary lavage fluid.
      As some other dissemination assessment techniques showed important prognostic
      value, the cytologic analysis of the axillary lavage fluid also seems to be a
      prognostic parameter.

PMID- 17438895
TI  - [The value of transvaginal ultrasonography in the follow-up of postmenopausal
      women's endometrium].
AB  - Endometrial cancer remains, today, a serious problem, especially for
      postmenopausal women. The aim of our study was to evaluate the utility of the
      transvaginal ultrasound examination in the management of the endometrial
      abnormalities in postmenopausal women. We included, in a prospective cohort, 49
      successive postmenopausal women: 34 with metrorrhagia (group I) and 15 with no
      symptoms (group II) and we compared the results obtained by ultrasound
      examination, Pap smear and endometrial biopsy. Patients in group I had a higher
      frequency of risk factors and thick and abnormal endometrium. Unlike Pap smear,
      ultrasound examination and biopsy had comparable values. We could conclude that
      transvaginal sonography is a reliable technique for the endometrium evaluation in
      the postmenopausal women. Ultrasound exam could select the cases (without any
      symptoms) for endometrial biopsy and detect associated gynecological pathology.

PMID- 17438896
TI  - [Reconstructive surgical procedures in the treatment of tissue defects of cervico
      facial oncological pathology].
AB  - The frequency of head and neck cancer is on an ascending path and a lot of cases
      are discovered in advanced stages. The treatment is difficult and requires the
      use of reconstructive methods to solve the tissue defects. The authors conducted
      a retrospective study on 121 cases solved in the ENT Department of "Sf. Spiridon"
      University Hospital Iasi hospitalized with oncologic pathology in advanced
      stages, between 2000-2004. The tissue defects after surgical excision were solved
      by different types of myocutaneous flaps, necessary to cover or reconstruct
      visceral or cervicofacial tissue defects. We insisted on difficulties and
      complications that can appear after this kind of oncological surgery. The results
      of this study generally prove the usefulness of the myocutaneous flaps in the
      treatment of the advanced head and neck cancer.

PMID- 17438897
TI  - [Gastrocolic fistulas. Review of three cases].
AB  - Gastrocolic fistula (GCF) is a rare and severe lesion appearing traditionally as
      a complication of inadequate gastric surgery or in the context of stomach or
      colon malignancy, but actually arising from many different gastrointestinal
      conditions. Three patients with GCF, admitted and operated in our clinic, are
      presented. The first case, a man aged 36 years, was a classical one, with a
      G(jejuno)CF appearing three years after a gastrectomy with Reichel-Polya
      reconstruction for duodenal ulcer, resolved by a "revision gastrectomy" en block
      with segmental resection of the jejunum and transverse colon. The second case,
      also a man aged 43 years, presented a spontaneous GCF determined by a gastric
      carcinoma, that required an en block enlarged gastro-colectomy. The last case, a
      61 year-old woman, presented three weeks after an emergency concomitant
      cholecystectomy and appendicectomy, with clinical manifestation suggesting a
      subphrenic abscess. Although a contrast-enhanced CT revealed a communication
      between the great curvature of the stomach and the splenic flexure of the colon,
      no fistula was found at laparotomy (spontaneous healing?). However, the terminal
      ileum and ascending colon had a suggestive appearance of Crohn's disease
      (confirmed by pathology) and a right colectomy was done. Excepting the rare
      situation of spontaneous or after medical treatment healing, the mainstay therapy
      of GCF is the case-adapted surgery.

PMID- 17438898
TI  - [Prenatal diagnostic of congenital unilateral hydronephrosis with megaureter--a
      case presentation].
AB  - Unilateral mild hydronephrosis with ureteral dilatation is a condition that can
      be detected by careful prenatal ultrasound examination. We present such a case,
      in a 26 year pregnant woman with hereditary antecedents (mother with Ombredan
      disease). The fetal ultrasound at 34 weeks indicated a left anechogenic sinuous
      image, identified as dilated ureter, and connected to a grade 2 hydronephrotic
      kidney. Normal data regarding the other kidney and the bladder made us recommend
      a close follow-up, considering this case as with a good prognosis. After birth,
      reassessment was favourable, and at 1 year follow-up the child was in good
      condition, and the kidney functional. We conclude that this case is a unilateral
      congenital megaureter, of probably obstructive origins, with a mild
      hydronephrosis. A good outcome was suggested by the late diagnostic, unilateral
      condition, and normal fetal ultrasound description regarding morphology, biometry
      and amniotic fluid.

PMID- 17438899
TI  - [Effects of sudden abdominal decompression on the cardio-pulmonary function].
AB  - The authors present certain observations on a female patient with large uterine
      fibroma, HTA and obesity who underwent a cardiac stop in the moment of excising
      fibroma out of the peritoneal cavity ; she was resuscitated but the cardiac stop
      repeated for two times and finally she survived. Four months later, total
      hysterectomy with bilateral adnexectomy was performed with no incidences. We
      discuss on the intraabdominal pressure increase effect (IAP) more than 10-15 mmHg
      determining an intraabdominal hypertension (IAH) with negative effects on the
      tissular and cell perfusions and producing an "abdominal compartment syndrome"
      (ACS). Intraabdominal hypertension has a significant consequence on the cardio
      vascular system by reducing the cardiac pre-charge, cardiac contractility
      decrease, cardiac flow decrease and post-charge increase. All these changes
      reduce the heart ability to fit to sudden abdominal decompression and producing a
      vacuum into the abdominal vessels and stopping the heart by a more significant
      reducing of the pre-charge and cardiac flow.

PMID- 17438900
TI  - [Risks and difficulties in the treatment of malignant tumors of the lower face].
AB  - The extensive malignant tumors of the face impose numerous problems regarding the
      surgical treatment due to, on one hand to their extension and on the other hand,
      to the aggressivity of the histological entity. The histopathology and the
      grading of these tumors are very helpful in orientating the specialist to choose
      the best therapeutic protocol in each case.

PMID- 17438901
TI  - [Retrograde intramedullary fixation of distal femoral fractures].
AB  - Distal femoral fractures are a therapeutical challenge due to the high rate of
      complications. Classic implants like DCS or condylar blade plate require large
      incisions and also generate a high rate of malunion and nonunion. Retrograde
      femoral nail is an implant recently used in our department and the purpose of
      this paper is to present the surgical technique. We treated 6 patients using this
      method and results were very good in all cases. Operative steps are presented:
      preoperative planning, incision (we used open technique), guide insertion, nail
      insertion and screw looking. A review of literature shows that there are many
      authors considering that internal fixation with retrograde nail is a good choice
      in distal femoral fractures.

PMID- 17438902
TI  - [Recruiting maneuvers in ALI/ARDS].
AB  - Mechanical ventilation, a life saving procedure in ARDS aims to optimally
      ventilate the patient and to avoid at the same time the ventilator induced lung
      injury (VILI). In ARDS the lung contains a variable portion of collapsed alveoli
      witch impair the normal oxygenation. While the positive end-expiratory pressure
      (PEEP) can prevent further alveolar collapse the recruiting maneuvers are able to
      open the already collapsed ones. Multiple recruiting maneuvers are reported in
      the literature but there is no consensus regarding the optimal one(s), as each
      maneuver is only partially efficient and has several down falls. While in animal
      studies theses maneuvers have proved their efficiency and safety, there are not
      enough humans studies to guide the decision on how, when and which technique
      should be used.

PMID- 17438903
TI  - [Intra-abdominal pressure on the functions of abdominal and thoracic organs].
AB  - A certain pressure exists within closed cavities such as the skull, the abdomen,
      the thorax, therefore allowing a good supplying to the organs inside. Variations
      of intraabdominal pressure (IAP) over 10 mmHg will cause an intraabdominal
      hypertension (IAH) altering both the tissue and cell blood pressure and having an
      impact on some organs, thus achieving the co-called "abdominal compartment
      syndrome" (ACS). Intraabdominal pressure increase can lead to some negative
      effects on both the intra- and extra-abdominal organs such as: cardiovascular,
      renal, respiratory and digestive systems. ACS is defined as a pathologic status
      originating from the intraabdominal pressure increase over 20-25 mmHg, values
      determining a perfusion pressure decrease within the abdominal organs (APP). IAP
      followed by IAH occurs in ileus, abdominal tumors, intraabdominal hemorrhage and
      in some morbid conditions: obesity, hepatic cirrhosis with ascites, pregnancy.
      Central nervous system is affected as an IAP increase will cause an intracranial
      pressure increase (ICI) with cell perfusion decrease; it occurred by means of the
      jugular vein compression and the central venous flow reducing. As a conclusion,
      IAP increase is associated by clinical manifestations with local and general
      effect finally producing organic failure, too.

PMID- 17438904
TI  - [New trends in the scientific anthropo-cultural psychiatric expertise].
AB  - Starting from the "epistemological naturalization of sciences of life", the
      authors present the complex content of medico-legal psychiatric examination, from
      which will result its scientific structure. The ontological, epistemological,
      hermeneutical and axiological content of this type of examination emphasize its
      methodological structure in the purpose of combining in a creative way its
      humanistic and scientific features.

PMID- 17438905
TI  - 99mTc isonitrils biophysical aspects in pulmonary tuberculosis. Part I. In vivo
      evaluation of 99mTc MIBI and 99mTc Tetrofosmin biophysical localization
      mechanisms.
AB  - The aim of our study was to compare the role of lung perfusion scintigraphy with
      1mTc MIBI and 99mTc Tetrofosmin (Mw) for the initial diagnostic evaluation of
      pulmonary tuberculosis-PTB). MATERIAL AND METHOD: Two groups of new PTB diagnosed
      patients, without treatment, were studied: group I--41 patients were imaged with
      99mTc MIBI (sex ratio men:women = 17:24, mean age 25 years, 26 positive
      Mycobacterium Tuberculosis (MT) smears, 15 negative MT smears), group II--40
      patients were imaged with 99mTc Mw (sex ratio men:women = 21:19; mean age: 32.5
      years; 31 positive MT smears, 9 negative MT smears. Both groups received a 7.4
      MBq (0.2 mCi)/kg radiotracer i.v. dose. Two anterior planar 3000000 counts/image
      on the thorax, one at 15 minutes and the other at 60 minutes after radiotracer
      administration and a SPECT acquisition were performed. For 99mTc Mw, three extra
      images were, in addition, performed, at 5, 90 and 120 minutes, in order to
      compare its kinetic with the known 99mTc MIBI kinetic. Clinical, radiological
      (Rx) and bacteriologic assessments of the patients were also done. RESULTS:
      Qualitatively, radiotracer uptake classification was coded: without uptake (-);
      low uptake (+); moderate uptake (++); high uptake (+++). Three identical interest
      regions were drawn: on the pathologic site, on a homolateral normal pulmonary
      field and on a myocardial field. The quantification has been assessed using three
      indexes (counts/pixel): I1= lesion/ normal; I2 = lesion/heart; I3 = normal/heart.
      We have found a significant difference between the mean value of I1:1.484, in the
      case of 99mTc MIBI versus 1.95 in the case of 99mTc Mw. The sensibility of the
      method was 96% for 99mTc MIBI versus 94% for 99mTc Mw, the specificity being 86 %
      for 99mTc MIBI versus 88% for 99mTc Mw. CONCLUSION: Both radiotracers are useful
      for the imaging evaluation of PTB, and can give evidence of new sites, related to
      radiology. The contrast between pathologic and normal uptake is more evident in
      99rTc Mw images than in 99mTc MIBI images, how it was demonstrated by the index
      quantification. The in vivo uptake kinetic for 99mTc Mw seems to be similar with
      that of 99mTc MIBI for the first 60 minutes but, at 120 minutes showed delayed
      washout. This can be useful in the differential diagnosis from other lung disease
      where the radiotracer kinetic is different.

PMID- 17438906
TI  - [Vascular molecular markers for determination of disease free survival (DFS) of
      breast cancer].
AB  - The heterogeneity of the evolution of breast cancer complicates patient
      management. The use of vascular markers as prognostic factors is a new and
      promising tool in medical oncology. Research data of the current decade
      demonstrate that angiogenesis plays substantial role in growth and spread of
      malignant tumor. At present, immunohistochemical determination of intratumoral
      microvascular density represents one of the more promising new prognostic
      indicators in breast cancer that needs to be further investigated to identify and
      standardize the method of choice to be tested in prospective clinical studies.
      Consequently markers of angiogenic activity have receiving increasing attention.
      By analyzing the evolution of 209 cases of breast cancer enrolled in a
      prospective study reaching the 5th year of follow up, we provide herein data
      supporting that Factor VIII and CD34 could be reliable markers for prognosis of
      DFS. Tumors with lower expression of Factor VIII and CD34 have a better
      prognostic and lower potential metastatic. The Factor VIII comparative with CD34
      represents a more faithful prognostic marker. Angiogenesis markers have also
      become a putative therapeutic target.

PMID- 17438907
TI  - [Cigarette smoke extract induces endothelium dysfunction in isolated rabbit
      pulmonary arteries via an oxidative mechanism].
AB  - In early stages of COPD, lacking hypoxemia, pulmonary arteries yet show
      endothelial abnormalities. This vascular impairment could be assigned to noxious
      effects of some cigarette smoke components. The aim of the present study was to
      investigate the effect of cigarette smoke extract (CSE) on endothelial vasomotor
      function in isolated rabbit pulmonary arteries in the presence or absence of a
      natural antioxidant with superoxide dismutase activity (SODn). After incubation
      of vascular rings with CSE (5% in organ bath) vascular responses to acetylcholine
      (endothelial-dependent vasodilator agent) and sodium nitroprusside (endothelial
      independent vasodilator agent) were evaluated. Our results showed the impairment
      of endothelial dependent vasodilation (maximal relaxation expressed as % was
      28.32 +/- 10.15 vs. 46.36 +/- 8.04 in the group coincubated with SODn, p < 0.01)
      while endothelial independent relaxation was preserved (maximal response
      expressed as % was 95.04 +/- 7.40 vs. 97.54 +/- 4.58 in the group coincubated
      with natural antioxidant, p = NS). In conclusion, the hydrosoluble components of
      CSE induced endothelial vasomotor function impairment, most probable, via an
      oxidative mechanism.

PMID- 17438908
TI  - [Modulation of the platelet function by diet supplemented with flaxseed and
      vitamin E in diabetic hamsters].
AB  - The aim of our study was to assess the platelet aggregation and adhesiveness in
      diabetic and non-diabetic hamsters receiving or not a diet supplemented with
      flaxseed (rich in'alpha-linolenic acid) and vitamin E. Forty-eight 6-month old
      male Golden Syrian hamsters were distributed in either control (non-diabetic) and
      diabetic group (STZ, 50 mg/kg body weight, i.p.). The control and diabetic groups
      received one of the following diets 1. control diet (rich in linoleic acid) ; 2.
      diet supplemented with flaxseed (15% flaxseed); 3. diet supplemented with
      flaxseed and vitamin E (40 mg/kg body weight); 4. diet supplemented with flaxseed
      and vitamin E. We measured platelet aggregation and adhesiveness after 20 weeks
      from the beginning of the experiment. In diabetic hamsters, only the diet
      supplemented with both flaxseed and vitamin E resulted in significant reduction
      of platelet aggregation (5.5 +/- 5.2 mOD/min vs. 10.3 +/- 3.8 mOD/min) and
      adhesiveness (9.7 +/- 3.9% vs. 23.4 +/- 10.6%) as compared to diabetic animals
      fed with control diet. In non-diabetic animals, flaxseed rich diet alone was
      efficient in lowering platelet functions as compared to linoleic acid rich diet.
      Mixed diet containing flaxseed and vitamin E was more effective than flaxseed
      alone in modulating platelet functions in diabetic hamsters. These observations
      indicate that vitamin E exerts important effects on determinants of oxidation and
      platelet functions and potentiates the flaxseed effects in experimental diabetes.

PMID- 17438909
TI  - [Diagnostic testing in fragile X syndrome].
AB  - Fragile X syndrome is the most common inherited cause of mental retardation. It
      is caused by a progressive expansion of polymeric (CGG)n trinucleotide repeats
      located on the FMR1 gene at Xq27.3. The spectrum of clinical involvement is
      broad, clinical diagnosis being difficult especially in young children. Hence,
      all cases of mental retardation without obvious cause should be tested for
      fragile X syndrome; the relatives of such a case need to be offered genetic
      counseling. Cytogenetic and molecular diagnostic tests are available. Recently,
      an immunocytochemical test has been described to identify fragile X patients,
      based on detection of FMR1 protein in cells using a monoclonal antibody. This
      method is used for screening, PCR based tests and Southern blot hybridization
      being the diagnostic tests for mutation and pre-mutation detection. Prenatal
      diagnosis is possible.

PMID- 17438910
TI  - [The utilization of Dacron as interposition material in the treatment of the
      temporomandibular ankylosis--retrospective study: 1993-2005].
AB  - The treatment of temporomandibular ankylosis, indifferently by anatomoclinical
      type or etiologic factor (trauma, infection, rheumatism), is exclusively
      surgical. The frequent indication in the temporomandibular ankylosis of types I
      and II Topazian remains the neo-articular modeling osteotomy with or without
      interposition. A clinical and retrospective study of 25 patients diagnosed with
      temporomandibular ankylosis (unilateral or bilateral) was performed. The patients
      were operated between 1993- 2005 by interpositional arthroplasty after resection
      of the joint osseous block. From 32 surgical procedures in temporomandibular
      ankylosis, the Dacron was used for 29 interventions. The qualities of this
      material were confirmed by good results obtained after 1-12 years of following.
      The mobility of the mandible and postoperative mouth opening were in normal
      limits with lack of complications or recurrences. The technique is simple and the
      interposition material is well tolerated by the body. The Dacron texture is soft,
      elastic, resistant with physically and chemically stable. It is easy to be
      modeled, perfectly adaptable on resting osseous mass, and it is integrates intra
      new joint by penetration of the connective fibrous in itself. Given these facts,
      the interposition material of Dacron plays the role of the fibrocartilage in the
      temporomandibular joint.

PMID- 17438911
TI  - [Canine tooth transposition study on a group of patients orthodontically
      treated].
AB  - The dental transposition is an eruption anomaly, which occurs in this process
      towards the final stage and that represents the switching of 2 teeth that are
      next to each other. The tooth that most often is involved in transposition is the
      canine tooth, most frequently the upper one, which switches places either with
      the first premolar either with the lateral incisor. Under a clinical aspect, the
      transposition can be total (complete) or partial (incomplete), the latter
      reported both for crowns and roots. The clinical manifestation of the anomaly
      imposes the characteristic signs and the individualized therapeutical attitude.
      The dental transposition must be differentiated within the eruption anomalies
      from the transmigration, which defines the displacement of a tooth inside the
      bone beyond the median line, this tooth usually being the lower canine. Our
      study, which was conducted on a small group of 34 patients, shows the results of
      the analysis of the anomaly versus the gender, the type of the transposition, the
      affected maxillary etc.

PMID- 17438912
TI  - [A maxillary premolar reconstruction with a glass fiber reinforced post].
AB  - This paper presents the case of a 37 years old female patient who needed a
      reconstruction of an endodontic treated' second maxillary premolar. The patient
      presented large areas of occlusal abrasion caused by bruxism, therefore the
      solution consisted of a reconstruction with a non-metallic post reinforced with
      glass fibers. In such cases, the excessive occlusal forces developed by bruxism
      can produce a radicular fracture if the tooth would be reconstructed with a rigid
      metallic post. The glass-fiber reinforced post has some important qualities,
      which render it more suitable in most clinical cases: it is easy to use; has the
      ability to bond with restorative resins; decreases the risk of tooth fracture and
      provides better esthetics.

PMID- 17438913
TI  - [Epidemiology of viral hepatitis B in the Iasi County in the interval 1990-2005].
AB  - Viral hepatitis and especially hepatitis B (HVB) continue to represent major
      health problems. In Romania, the morbidity from HVB is still 3 to 5 times higher
      than in Western Europe and North America. In the Iasi County, the effectiveness
      of the preventive measures is proven by a curve of morbidity values close to or
      even below those recorded at national level. As a result of the preventive
      interventions, in the interval 1996-2005, the morbidity from HVB was lower in all
      age groups as compared to the interval 1990-1995. The significant decrease in
      morbidity following the introduction of a vaccination program and the
      preservation of a constantly descending trend reflect the favourable change in
      the epidemiological process of HVB.

PMID- 17438914
TI  - Dietary imbalance in some communities of Transylvania.
AB  - The relationship between diet intake and nutritional needs may be the most
      important factor which influences the health status from a nutritional point of
      view. Essential for maintaining health status is to keep this two constituents in
      balance. To evaluate the diet and nutritional status, we enrolled in an
      observational cross-sectional study, a population of 312 people, 202 females and
      110 males, categorized by age (20-40 years, 41-65 years and over 65 years) and by
      physical exertion (low, medium and high). The food intake was under reference
      values in the case of vegetable proteins (-9.99%), carbohydrates (-24.17%) and
      energy (-10.29%) and over the reference values of animal fats (+24.15%) in the
      female population and under the reference values of carbohydrates (-24.44%) and
      over these values in the case of animal fats (+29.83%), total fats (+13.78%) and
      animal proteins (+15.02%) in the male population of the study. The investigation
      of the arterial pressure shows that 18.5% of females and 13.5% of males have
      arterial hypertension which means that for the entire study population the
      incidence was 16%. This data correlated with the values of body mass index which
      were over the normal values in 35.5% of females and 23.5% of males, and in 32.38%
      of the whole study population, indicated a high percent of overweight and
      together with the deficiency from the lipids metabolism shows the significance of
      the effect of the over-intake of fats, especially from animal origin, on the
      health status and in particular, on the cardiovascular system. On the other hand,
      the body mass indices were found under the low limits in 23.5% of females and in
      15.3% of males, and in 21.3% of the study population, thus the correlation with
      the low carbohydrate and energy intake is obvious.

PMID- 17438915
TI  - [Soliciting a model of a child emergency care unit in road accidents in the year
      2005].
AB  - This paper describes the specific model of burden due to child road traffic
      injuries upon the emergency care unit from a university paediatric hospital
      during 2005 year. A total number of 193 road trauma cases required emergency care
      to this hospital. Distribution by seasons pointed out the highest number in
      summer (31.1%) and comparing the observed repartition by seasons with an expected
      symmetrical repartition there have been obtained significant differences between
      seasons (p < 0.02). The regular number of cases was 1-2 daily. The burden of road
      trauma was unequal, more boys (58.5%) being injured than girls and children
      living in urban areas recorded similar rates of injuries with those from rural
      areas. The median age of injured children was nine years, approximately one third
      of cases being included in 5-9 years age group. The leading non-fatal injuries
      requiring emergency care as a result of road traffic collisions have been:
      multiple trauma--166, intracranial injury--128, fractured lower limbs--31,
      fractured upper limbs--20 cases. Approximately one third of these cases required
      admission in hospital for complex care, one third have been referred to another
      hospital (neurosurgery and maxillo-facial clinic) and one third have been
      discharged after 24 hours of hospitalized monitoring. In conclusion, more road
      traffic injuries arrived in the emergency care unit of the studied university
      paediatric hospital during summer without a specific distribution by weekdays,
      but with a higher probability of being a boy aged 5-9 years, presenting multiple
      trauma especially intracranial injury and requiring specialised hospital care.

PMID- 17438916
TI  - Immune status to polioviruses in the child population of Romania between 2002
      2005 as indicated by serological investigation in cases of acute flaccid
      paralysis (AFP) and facial paralysis (FP) and its use as a "national reference
      value" to evaluate the vaccination coverage in particular groups of healthy
      children.
AB  - Although the European region is polio free since 2002, the risk of importation
      from endemic regions remains present and a high level of population immunity must
      be maintained. In Romania during the period 2002-2005, 101 FP cases, 91 AFP cases
      and 29 healthy contacts (living in groups with low social and sanitary status,
      relatively low vaccination coverage named "at risk") could have been investigated
      serologically. Antibody prevalences for poliovirus types 1, 2, and 3 were: 97.2%,
      98% and 81.2% for FP cases; 96.7%, 94.5% and 85.7% for AFP cases, and 85.7%,
      82.1% and 53% for the group of healthy children at risk. The risk of the
      emergence and spread of cVDPVs remains present especially in "at risk" groups
      with the gaps in immunity, even in countries where indigenous wild polioviruses
      have already been eradicated.

PMID- 17438917
TI  - Oral streptococcal strains isolated from odontogenic infections and their
      susceptibility to antibiotics.
AB  - The aim of this study was to identify at species level and to investigate the
      antibiotic susceptibility of oral streptococcal strains isolated from 100 pus
      samples collected from Romanian patients with different odontogenic infections.
      The isolates were identified at species level using the Rapid ID 32 STREP system
      and their susceptibility was testing by the Etest, against: penicillin G,
      ampicillin, erythromycin, clindamycin and tetracycline. For the investigation of
      erythromycin resistance phenotype the disk diffusion test was used. The isolates
      belonged to several species, with Streptococcus anginosus and Streptococcus
      oralis predominating. Reduced susceptibility to beta-lactam antibiotics was found
      only among the isolates belonging to S. mitis and S. sanguinis groups. Resistance
      to erythromycin was detected among all species, except for: S. constellatus, S.
      intermedius and S. gordonii, and the M phenotype was established, while
      resistance to tetracycline was detected within all species but S. gordonii. In
      contrast, clindamycin was fully active. As most odontogenic infections are mixed
      infections, often involving strictly anaerobic bacteria, which are frequently
      beta-lactamase producers, the association of a penicillin and a beta-lactamase
      inhibitor, like Amoxiclav, is recommended when the antimicrobial treatment is
      necessary.

PMID- 17438918
TI  - Correlation between linezolid zone diameter and minimum inhibitory concentration
      values determined by regression analysis.
AB  - Linezolid is a new synthetic antibiotic belonging to the oxazolidinone class,
      available for the therapy of gram-positive infections, caused by methicillin
      resistant staphylococci, vancomycin-resistant enterococci and penicillin
      resistant pneumococci. The aim of the study was to determine the in vitro
      activity of linezolid against staphylococci strains and also to determine the
      relationship between the minimum inhibitory concentration (MIC) and inhibition
      zone diameter by calculating the regression analysis. We tested one hundred S.
      aureus isolates, obtained from healthy persons (naso-pharyngeal swabs) during
      2005 year. The antibiotic susceptibility of strains was determined by disk
      diffusion standardized method and by agar dilution method using a multipoint
      inoculator. The relationship between the diameter of the inhibition zone produced
      by a linezolid disc impregnated with a fixed amount (30 eg) was determined by
      regression performed with the least squares method, considering the log2 of the
      minimum inhibitory concentrations (MICs) as the independent variable and the zone
      diameter as the dependent variable. The MIC values expressed in logarithmic form
      are plotted against inhibition zone diameter (arithmetic scale) of the same
      strain. The activity of linezolid against staphylococci was very good, with MIC
      90 of 1 mg/l. All strains were fully sensitive. The regression line for linezolid
      passes through a continuous series of points that all are approximately located
      on the a straight line. For each of the MIC values the differences result no
      greater than 23 mm in diameter sizes were registered. Regression equation was y= 
      0.188x + 8.048. In conclusion, the regression line analysis calculated for
      linezolid, demonstrates a significant correlation between MIC values and the
      inhibition zone diameters obtained by a 30 mg disc.

PMID- 17438919
TI  - [Contributions to chemical study of the raw polysaccharide isolated from the
      fresh pressed juice of white cabbage leaves].
AB  - In traditional medicine fresh pressed juice of white cabbage leaves is used in
      the treatment of many diseases in which immunity disorders are involved: diabetes
      mellitus, rheumatism, gastric ulcer, cirrhosis, cancer. The efficiency of fresh
      cabbage juice might be due to an immunomodulatory activity. Polysaccharides are
      hydrosoluble compounds for which there have been pointed out immunomodulatory
      effects in recent years. This is the reason why a raw polysaccharide was isolated
      from the fresh pressed juice of white cabbage leaves. The raw polysaccharide was
      purified and submitted to a chemical study based on analysis of proteic component
      (quantification of total nitrogen, total proteins and soluble proteins) and
      analysis of polysaccharides component (isolation and characterization of main
      polysaccharides fractions, identification of main sugar components,
      quantification of uronic acids). Further in vitro studies will evaluate the
      immunomodulatory capacity of this polysaccharide.

PMID- 17438920
TI  - [New biological active derivatives of indomethacin and acetylsalicylic acid.
      Synthesis, physico-chemical characterisation and structure validation].
AB  - It is well known that niflumic acid glycinamide has a good antiinflammatory
      action useful in gum inflammatory diseases. The objective of this study was to
      obtain new glycinamides of acetylsalicylic acid and indomethacin, which could
      have a better antiinflammatory action than niflumic acid glycinamide. The study
      presents the synthesis, physico-chemical characterisation and structure
      validation of these glycinamides.

PMID- 17438921
TI  - Morphological changes in the liver after the administration of piroxicam and its
      complexes with Bio-Ions Cu (II), Co (II), Zn (II) to the rats.
AB  - In this research we present the results of the liver histopathological
      examinations after the administration of the Piroxicam (Pirox) and its complex
      combinations with metal bio-ions Cu (II), Co (II), Zn (II) to rats (White Wistar,
      150-180 gr.). The results of the histological investigations are presented
      separately for each compound revealing the modifications after 24 hours and after
      7 days. The hepatic lesions are noted in the case of Zn-Pirox after 24 hours and
      after 7 days, as well. The complexes Cu-Pirox and Co-Pirox don't produce hepatic
      modifications either after 24 hours or after 7 days according to our histological
      investigations.

PMID- 17438925
TI  - [Professional burnout syndrome, an increasing reality].

PMID- 17438926
TI  - [Practical approach to professional burnout].

PMID- 17438927
TI  - [Preventing and caring for professional burnout].

PMID- 17438928
TI  - [Hardiness, a resource for coping with stress].

PMID- 17438929
TI  - ["Salutogenic" personalities].

PMID- 17438930
TI  - [To build for oneself an armor of light and pride].

PMID- 17438931
TI  - [Patient-controlled morphine analgesia pump].

PMID- 17438932
TI  - [Diabetic education workshops in Roanne].

PMID- 17438933
TI  - [Nurse's role in a clinical research unit].

PMID- 17438934
TI  - [Unhealthy kilos].

PMID- 17438935
TI  - [Enoxaparine].

PMID- 17438936
TI  - [Fasting and post-prandial glycemia].

PMID- 17438937
TI  - [Prevention and campaign against abuse with Alma France].

PMID- 17438938
TI  - Alginate-cellulose sulphate-oligocation microcapsules: optimization of mass
      transport and mechanical properties.
AB  - Microcapsules based on polyelectrolyte complexation, where the inner phase
      involves a blend of alginate and sodium cellulose sulphate (SCS), have mechanical
      and transport properties which are relatively insensitive to the chemical
      composition of the rigid polyanion. Specifically, the bursting force of 400- and
      1000 microm microcapsules increase slightly with the degree of substitution of
      the SCS, though the molar mass of the SCS appears to influence the transport
      properties more strongly than its composition. The concentration of the sodium
      chloride in the gelling batch can be varied rather extensively, with optimum
      properties at approximately half (i.e. 0.5 M) the level typically employed for
      the formation of cell-containing microcapsules. This indicates that the
      microcapsule properties can be tuned for biocompatability, without concern that
      changes to the polymer microstructure or reaction process conditions would
      adversely influence the bursting force or molar mass cut-off of the capsules. The
      alginate-SCS blend, which is typical equimass, can be slightly increased in
      favour of the SCS (to 55 wt%) if one seeks to mechanically optimize the system.
      The substitution of the oligocation polymethylene-co-guanidine with pDADMAC seems
      strongly undesirable. Similarly, the replacement of SCS with
      sulphoethylcellulose, while possible, offers no important advantages. The overall
      optimum conditions appear to be for a SCS with a DS of 2, prepared at 1.2 wt% of
      total cation with alginate. The ideal ratio, for mechanical and transport
      properties, of SCS to alginate is 55:45 (wt:wt), which represents a subtle
      modification from the classical formulation with very good biocompatability.

PMID- 17438939
TI  - Preparation and properties of electrophoretic microcapsules for electronic paper.
AB  - This paper shows two types of microcapsules used for electrophoretic display. One
      is prepared by in-situ polymerization which is based on urea, melamine and
      formaldehyde and another by complex coacervation, which is composed of gelatin
      and gum Arabic. Microcapsules attract interests of many research groups for
      longer lifetime of electrophoretic display by reducing agglomerization or lateral
      movements of nanoparticles. The gelatin microcapsules were more attractive in
      providing more uniform microcapsule coverage on electrodes due to their
      flexibility as compared to the melamine-urea microcapsules. The properties of
      microcapsules were characterized by FTIR, OM, SEM and TGA. Migration of
      nanoparticles in the two types of microcapsules was also observed when an
      electric field was applied.

PMID- 17438941
TI  - Investigating the effects of surfactants on the size and hydrolytic stability of
      poly(adipic anhydride) particles.
AB  - The present study investigates the effects of surfactants (<0.01% v/v) on the
      size and hydrolytic stability of poly(adipic anhydride) (pAA) micro- and
      nanospheres fabricated using a modified phase inversion technique. Overall,
      surfactants increased the output yield by roughly 20%. Lecithin produced the
      greatest reduction in the volumetric particle size (dvol) compared to particles
      fabricated with no surfactant (dvol = 530 +/- 300 nm and 2.2 +/- 1.1 microm,
      respectively). In addition, sorbitan monooleate produced spheres with smaller
      numeric diameters (dnum) than the control but appeared to induce aggregation
      (dvol = 7.7 +/- 12.5 microm). The dnum and dvol were not dependent on the
      hydrophobicity of the surfactant (R2 = 0.36 and 0.03, respectively) or the
      apparent surface tension of the non-solvent (NS) phase (R2 = 0.44 and 0.04,
      respectively). In addition, quantitative DSC and FT-IR analysis confirmed that
      altering the particle size could also influence the hydrolytic stability of pAA.

PMID- 17438940
TI  - Polymethylene-co-guanidine based capsules: a mechanistic study of the formation
      using alginate and cellulose sulphate.
AB  - Capsules have been prepared based on a polyanion blend of sodium alginate and
      sodium cellulose sulphate, gelled in the presence of calcium chloride and sodium
      chloride. In a second step a membrane was formed via the addition of
      polymethylene-co-guanidine (PMCG), an oligocation. A mechanistic study examined
      the influences of pH, ionic strength, gelation and reaction times as well as the
      molar mass of the polyanions on the transport and mechanical properties. The
      ratio of alginate-to-cellulose sulphate in the polyanion blend was also varied
      and it was found that both mechanical resistance to compression as well as the
      pore size of the membrane decreased as the percentage of cellulose sulphate was
      reduced. The maximum mechanical strength was observed to correspond to the
      minimum in viscosity of the polyanion blend with, for low NaCl levels, a 3:1
      alginate:cellulose sulphate level providing the largest resistance to
      deformation. The ability to decouple the molar mass cut-off and mechanical
      resistance is viewed as an important advantage of alginate/cellulose
      sulphate/PMCG capsules. Capsules were transplanted into mice to a maximum of 102
      days, after which animals were sacrificed and capsules retrieved. Over 90% of the
      capsules were recovered from the peritoneal cavity with the mechanical properties
      of the explanted capsules observed to decrease as a function of implantation
      time, likely as a result of ion exchange. The capsules were, however, relatively
      free from any rejection which is a quite unusual result for cation containing
      systems. It is believed that the reason PMCG-based microcapsules function well in
      vivo is that they provide a net negative charge on the surface. Higher molar mass
      polycations such as poly-L-lysine provide a net positive charge, inducing
      inflammation.

PMID- 17438942
TI  - Physicochemical properties of film-coated melt-extruded pellets.
AB  - The purpose of this study was to investigate the physicochemical properties of
      poly(ethylene oxide) (PEO) and guaifenesin containing beads prepared by a melt
      extrusion process and film-coated with a methacrylic acid copolymer. Solubility
      parameter calculations, thermal gravimetric analysis (TGA), scanning electron
      microscopy (SEM), modulated differential scanning calorimetry (MDSC), X-ray
      powder diffraction (XRPD) and high performance liquid chromatography (HPLC) were
      used to determine drug/polymer miscibility and/or the thermal processibility of
      the systems. Powder blends of guaifenesin, PEO and functional excipients were
      processed using a melt-extrusion and spheronization technique and then film
      coated in a fluidized bed apparatus. Solubility parameter calculations were used
      to predict miscibility between PEO and guaifenesin, and miscibility was confirmed
      by SEM and observation of a single melting point for extruded drug/polymer blends
      during MDSC investigations. The drug was stable following melt-extrusion as
      determined by TGA and HPLC; however, drug release rate from pellets decreased
      upon storage in sealed HDPE containers with silica desiccants at 40 degrees C/75%
      RH. The weight loss on drying, porosity and tortuosity determinations were not
      influenced by storage. Recrystallization of guaifenesin and PEO was confirmed by
      SEM and XRPD. Additionally, the pellets exhibited a change in adhesion behaviour
      during dissolution testing. The addition of ethylcellulose to the extruded powder
      blend decreased and stabilized the drug release rate from the thermally processed
      pellets. The current study also demonstrated film-coating to be an efficient
      process for providing melt-extruded beads with pH-dependent drug release
      properties that were stable upon storage at accelerated conditions.

PMID- 17438943
TI  - Preparation of microcapsules with self-microemulsifying core by a vibrating
      nozzle method.
AB  - Incorporation of drugs in self-microemulsifying systems (SMES) offers several
      advantages for their delivery, the main one being faster drug dissolution and
      absorption. Formulation of SMES in solid dosage forms can be difficult and, to
      date, most SMES are applied in liquid dosage form or soft gelatin capsules. This
      study has explored the incorporation of SMES in microcapsules, which could then
      be used for formulation of solid dosage forms. An Inotech IE-50 R encapsulator
      equipped with a concentric nozzle was used to produce alginate microcapsules with
      a self-microemulsifying core. Retention of the core phase was improved by
      optimization of encapsulator parameters and modification of the shell forming
      phase and hardening solution. The mean encapsulation efficiency of final batches
      was more than 87%, which resulted in 0.07% drug loading. It was demonstrated that
      production of microcapsules with a self-microemulsifying core is possible and
      that the process is stable and reproducible.

PMID- 17438944
TI  - The preparation of sustained release erythropoietin microparticle.
AB  - PURPOSE: Protein microencapsulation in biodegradable polymers is a promising
      route to provide for sustained release. The erythropoietin (EPO) microparticles
      are using human serum albumin (HSA) and poly-L-lysine (PK) as the protection
      complex to increased EPO integrity, entrapped efficiency and active EPO release
      by w/o/w solvent evaporation techniques. The optimum formulation development
      process was also reported by using FITC-OVA as a model protein. METHODS: The
      model protein FITC-ovalbumin and EPO are protected by human serum albumin and
      poly-L-lysine complex and encapsulated in 50:50 poly(DL-lactide-co-glycolide) by
      a w/o/w solvent evaporation method. Protein active integrity and degradation
      compound is measured by size-exclusion chromatography. Protein-loaded
      microparticle physical properties and in vitro active and degradation compounds
      release profile are characterized. RESULTS: High active integrity protein loading
      efficiency and particle yield of EPO or OVA-HSA/PK-loaded PLG microparticles are
      successfully produced by a w/o/w solvent evaporation method. Varied protection
      protein complex formulations and encapsulation processes are investigated. The
      high OVA model protein loading efficiency (80.2%), FITC-OVA content (0.24 microg
      mg(-1)) and yield (72.4%) are obtained by adding 100 microg mL(-1) FITC-OVA
      complex with 10% HSA/0.05% PK (Mw 1.5-3 kD) in the initial solution to protect
      the model protein. In vitro release profiles show more active OVA release from
      HSA/PK OVA-loaded than OVA-loaded only microparticles and also the amount of
      degraded protein that comes out after 3 weeks incubated in the PBS medium for OVA
      loaded only microparticles is observed. The same formulation and preparation
      process resulted in EPO loading efficiency (68.4%), EPO content (0.23 microg mg(
      1)) and yield (76.1%) for HSA/PK EPO-loaded microparticles. In vitro release
      profiles show active EPO sustained release over 7 days. Using HSA/PK as carried
      in the primary emulsion of EPO-loaded microparticles resulted in less burst
      release% than EPO-loaded only microparticles.

PMID- 17438945
TI  - Literature alerts.

PMID- 17438946
TI  - [To learn from teaching: the way to be an academic leader].

PMID- 17438947
TI  - [Mechanisms of aging and its theories].
AB  - The velocity of aging is rather different in various species, and even in various
      tissues and cells of the same individual. Both genetic and environmental factors
      affect aging process. It is evident that life expectancy mainly relates to
      environment, while maximum life-span of a species more depends on its genetic
      background. Poor environment possibly affects genes or their products and then
      influences the process of human senescence. As aspect of genetic causes, aging is
      not totally depends on one gene, but rather on the interaction of networks of
      activated or repressed genes and their products. DNA (especially, mitochondrial
      DNA) is not as stable as previously conceived. The stability of genetic
      substance, including genes, could be affected by stresses from external or
      internal environment, which are particularly induced by harmful substances, such
      as reactive oxygen species, leading to accelerate aging process.

PMID- 17438948
TI  - [Advances in cardiovascular system endocrine].
AB  - Bioactive substances secreted from various cells of heart and vessels play a very
      important role in functional homeostasis of cardiovascular system. Discoveries of
      new bioactive peptides not only boost the cognition of the diseases, but also
      have extensive clinically prospectives in preventing and treating cardiovascular
      diseases. Bioactive peptides secreted from cardiovascular system have both
      multiple forms and diverse functions. The functional complexities of peptides
      correlated with receptor, distribution and expression of receptor subtype, and
      splicing of gene. In additon, the multifunctions of peptides are concerned with
      other fragments of the same peptide precursor, and with the choices of the same
      ligend for multiple receptors.

PMID- 17438949
TI  - [Impacts of modern biology on drug discovery].
AB  - Drug discovery has been improved greatly by series of new ideas and new
      technologies as well as new approaches emerging in the postgenomic era. On the
      one hand, the theoretics of drug discovery become more comprehensive and more
      profound as the development of numerous new disciplines such as genomics,
      proteomics, transcriptomics, metabonomics, bioinformatics and system biology; on
      the other hand, the pathways for new drug discovery are broadened by the
      continuous improvement of technological platforms including computer-aided drug
      design, high throughput screening, high content screening, biochip, transgenic
      and RNAi technology. Based on the recent advances on the modern biology, in this
      article, we specially reviewed the impacts of modern biology on the process of
      drug discovery.

PMID- 17438950
TI  - [Progresses of prospects for hypoxic preconditioning].
AB  - Hypoxic preconditioning (HPC), a strategy of intrinsic cytoprotection developed
      in biological evolution, is designed to be motivated by repetitive exposure of
      organism, organ, tissue and cell to condition of hypoxia. The effect of HPC is
      broadened remotely to protect different organ-tissues in other regions (
      remote/ectopic HPC, r/e HPC ) and crossly to resist a variety of stresses other
      than hypoxia ( cross/ pluripotential HPC, c/pHPC ) from protection of original
      local in situ organ-tissue repeatedly exposed to hypoxia (local/in situ HPC, l/Ii
      HPC). More spaces for development of feasibility and applicability in the
      research on HPC would be expected based on the progresses recently available.

PMID- 17438951
TI  - [Roles of shear stress in atherogenesis].
AB  - Located between circulating blood and vessel wall, vascular endothelial cells
      (ECs) are constantly exposed to shear stress resulting from blood flow. The
      mechanical actions of shear stress can be detected by mechanosensors on ECs and
      converted into specific signaling pathways to mediate the structural and
      functional remodeling. Patterns of shear stress may contribute to the focal
      distribution of atherosclerotic lesions. Here, we review recent advances
      regarding the roles of shear stress in atherogenesis.

PMID- 17438952
TI  - [Effects of ACE2-Ang 1-7-Mas axis on blood vessel].
AB  - The recent identification of angiotensin-converting enzyme 2 (ACE2) and Mas
      receptor opened new recognition of renin-angiotensin system (RAS). ACE2, a
      homologue of angiotensin-converting enzyme (ACE) generates angiotensin 1-7
      directly through cleaving angiotensin II, or indirectly through angiotensin I in
      the body. Ang 1-7 exhibits vasodilatory and antiproliferative effects, and these
      effects were mainly mediated by Mas receptor. So ACE2-angiotensin1-7- Mas axis
      was considered a negative regulation in renin angiotensin system (RAS), and its
      significance has been implicated into hypertension and other cardiovascular
      diseases. The identification of the axis opens a new potential venue for further
      study and understanding of RAS.

PMID- 17438953
TI  - [Long-term regulation of arterial pressure and essential hypertension--II.
      Essential hypertension].
AB  - Although the mechanisms underlying the development of essential hypertension
      remain elusive, many observations point to the kidney as a primary actor and
      sodium as the main culprit (external factor) for development of hypertension.
      Dietary sodium has been existed for several thousands years in human being and it
      seems to be a civilized food habit. However, over the last few decades,
      experimental, observational and clinical data have continuously indicated that
      excess salt intake is positively associated with elevated blood pressure. It was
      also found that aged people is easier to be suffered from essential hypertension.
      By now, essential hypertension is frequently considered as a "civilized" disease,
      a disease of the kidney and the disease frequently occurring in the aged people.
      In the present mini review these features of essential hypertension are discussed
      in more details.

PMID- 17438954
TI  - [Potential role of regulatory T cells in pathogenesis of atherosclerosis].

PMID- 17438955
TI  - [Current progress on cellular oxygen sensors: the family of hypoxia inducible
      factor-1 prolyl hydroxylase].

PMID- 17438956
TI  - [The function of CAPS in Ca(2+)-triggered exocytosis of vesicle].

PMID- 17438957
TI  - [Role of semaphorins in neural development and synaptic plasticity].

PMID- 17438958
TI  - [Interactions between leptin and central glucose-sensing neurons in feeding
      control].

PMID- 17438959
TI  - [Effects of seizures on developmental astrocytic excitability].

PMID- 17438960
TI  - [The role of myofibroblasts on tissue fibrosis and the regulation of
      myofibroblasts].

PMID- 17438961
TI  - [An important marker of pancreatic stem cell--nestin].

PMID- 17438962
TI  - [The author of the year].

PMID- 17438963
TI  - [Forensic evaluation of persons with destructive behavior in the postwar Bosnia
      and Hertzegovina].
AB  - BACKGROUND/AIM: Different persons show forensic differences related to aggressive
      behavior in criminal and violation acts. The aim of this study was to forensicly
      analyze the influence of socio-dynamic conditions and stress in testing the
      forensic hypothesis of hetero-destruction, and analysis of persons with
      destructive behavior in Bosnia and Hertzegovina (B&H) in the period from 1996
      2005. METHODS: The experimental group consisted of 125 persons who had committed
      a crime according to the Criminal Law of B&H and, thus were under security
      measures or treatment The control group consisted of 125 persons who had
      committed a violation. The following psychometric tests/questionnaires were used
      in the study: Eysenek Personality Questionnaire (EPQ), Beck Anxiety Inventory
      (BAI) and Profile Index of Emotions (PIE). RESULTS: There were a significant
      difference between the respondents' groups related to gender (p < 0.01), while
      broken family, migration, and family comorbidity showed insignificant
      differences. EPQ test showed statistically significant differences between the
      groups for all four variables, and Beck test found significant differences only
      for some ones. PIE test proved the relations of the basic emotions confirmed by
      discriminative function. CONCLUSION: High level of hetero-destruction in crime
      was proven in the study. Criminal acts and violations were committed by the
      persons without psychopathology, as well as by the persons with mental diseases,
      which rendered a forensic responsibility and analysis of such an influence on
      behavior.

PMID- 17438964
TI  - [Reduction of myocardial hypertrophy after aortic valve replacement].
AB  - BACKGROUND/AIM: Aortic valve disease - stenosis and regurgitation are the cause
      of increased homodynamic stress of the left ventricle (LV) which then develops an
      adaptive mechanism of cardiac muscle hypertrophy. The aim of this study was to
      establish if aortic valve replacement procedure (AVR) reduces myocardial
      hypertrophy and if it does in what period of time. METHODS: Eighty-six patients
      who had been operated for AVR in the Clinical Centre of Serbia were included in
      this investigation. In the every patient the aortic valve had been replaced with
      a mechanical valve prosthesis. Transthoracic echocardiography examination (TTE)
      was performed in all of the patients before, and one week after the operation,
      while 22 patients were followed-up on a long-term basis. The LV mass was
      determined with the formula according to the Pen convention. RESULTS: In the
      tested group there was significantly more male than female individuals (n = 57
      66.3%, 29-337%). Twelve patients (14%) were operated for isolated aortic
      stenosis, 22 patients (25.6%) for aortic regurgitation, 48 patients (55.8%) for
      combined aortic valve disease, while 4 patients (4.7%0/) for endocarditis.
      Student t test did not show any significant difference in diastolic septal
      thickness before and after the operation (p = 0.88), while it did show that the
      difference in the LV mass before and after the operation was highly significant
      (p = 0.000). This test also showed that, taking the mass of 240 g as the border
      value for hypertrophy of LV, the reduction of LV mass between preoperative and
      early postoperative finding was not significant (p = 0.5), while the reduction in
      LV mass between late and early postoperative examination was statistically
      significant (p = 0.000). In 19 of 22 patients who were followed-up
      postoperatively over a long period (84 months after the operation) significant
      reduction of LV mass was registered. The mean time of the reduction was 27.5
      months. CONCLUSION: This study showed the presence of a significant reduction in
      the LV mass after AVR, and that the mean time required for this process was more
      than two years.

PMID- 17438965
TI  - [Functional effects of preserving the intercostobrachial nerve and the lateral
      thoracic vein during axillary dissection in breast cancer conservative surgery].
AB  - BACKGROUND/AIM: Conventional axillary dissection in breast cancer surgery
      implicates the section of the neurovascular elements passing through the
      dissected tissue: the intercostobrachial nerve (ICBN) and lateral thoracic vein
      (LTV). Preservation of the ICBN during axillary dissection is well documented in
      the literature, with slightly contradictory results of its influence to
      postoperative pain. There is no published data, as far as we know, on the
      functional effects of preserving the LTV. We supposed that ligation of the LTV
      contributes to the emergence of postoperative breast edema, which is common in
      breast cancer conservative surgery. The preservation of venous drainage could
      diminish the frequency of this undesired occurrence. METHODS: In a prospective
      study, 126 patients undergoing axillary node clearance for breast cancer of
      stages I and II were randomly selected for preservation of ICBN and LTV (n=65),
      or for conventional dissection (n=61). Sensory deficit, pain and breast edema as
      a dichotomized characteristics were examined in the first two weeks after the
      surgery. RESULTS: No difference in the number of dissected nodes was seen between
      the two groups (p = 0.7). The loss of sensitivity was significantly less common
      in the group randomized for ICBN preservation (16/65 vs. 30/61,p < 0.005), while
      there was no difference in the pain intensity and duration (49/65 vs 44/61, p >
      0.05). LTV was preserved in 22 patients in the group for preservation, and in
      none of the control group. Breast edema was registered in 33 patients from the
      group for preservation (51%) and in 37 patients from the control group (61%). The
      difference in distribution was not significant, and the same results were
      obtained when the frequency of breast edema in the group with preserved LTV (22
      patients, 10 of them without breast edema) was compared with the all others (p >
      0.05). CONCLUSION: The preservation of the ICBN significantly improved the
      functional effect of the axillary dissection for breast cancer by reducing
      sensory loss, while there was no difference in pain intensity and duration.
      Although we did not prove that the preservation of LTV prevents breast edema
      after conservative surgery for breast cancer, we think that more complex
      analysis, including parameters such as the extent of resection of breast tissue,
      the dimension and constitutional characteristics of the breast, tumor location,
      obesity, and further developments in surgical technique, would reveal at least
      discrete improvements in the functional results of this surgical approach.

PMID- 17438966
TI  - [Effect of acclimation on changes in water and electrolyte homeostasis in
      soldiers during exertional heat stress].
AB  - BACKGROUND/AIM: Exertional heat stress is a common problem in military services.
      The aim of this study was to exemine changes in body water and serum
      concentrations of some electrolites in soldiers during exertional heat stress
      (EHST), as well as effects of 10-day passive or active acclimation in a climatic
      chamber. METHODS: Forty male soldiers with high aerobic capacity, performed EHST
      either in cool (20 degrees C, 16 degrees C WBGT-wet bulb globe temperature), or
      hot (40 degrees C, 25 degrees C WBGT) environment, unacclimatized, or after 10
      days of passive or active acclimation. The subjects were allowed to drink tap
      water ad libitum during EHST. Mean skin (Tsk) and tympanic (Tty) temperatures and
      heart rates (HR) measured physiological strain, while sweat rate (SwR), and serum
      concentrations of sodium, potassium and osmolality measured changes in water and
      electrolite status. Blood samples were collected before and immediately after the
      EHST. RESULTS: Exertional heat stress in hot conditions induced physiological
      heat stress (increase in Tty, HR, and SwR), with significant decrease in serum
      sodium concentration (140.6 +/- 1.52 before vs. 138.5 +/- 1.0 mmol/l after EHST,
      p < 0.01) and osmolality (280.7 +/- 3.8 vs. 277.5 +/- 2.6 mOsm/kg, p < 0.05) in
      the unacclimatized group. The acclimated soldiers suffered no such effects of
      exertional heat stress, despite almost the same degree of heat strain, measured
      by Tty, HR and SwR. CONCLUSION: In the trained soldiers, 10-day passive or active
      acclimation in a climatic chamber can prevent disturbances in water and
      electrolitic balance, i.e. decrease in serum sodium concentrations and osmolality
      induced by exertional heat stress.

PMID- 17438967
TI  - [Prevention of osteoporosis].

PMID- 17438968
TI  - [Myocardial noncompaction--a rarity or something else].

PMID- 17438969
TI  - [Somatostatinoma of the Vater's papilla in a patient with von Recklinghausen's
      disease].
AB  - BACKGROUND: Somatostatinomas of the gastrointestinal tract secret hormon
      somatostatin which can cause "inhibitory syndrom" comprising diabetes mellitus,
      cholelithiasis and steatorrheic diarrhea. It is also secreted by the D cells of
      Langerhans's islands of the pancreas as well as endocrine cells of the stomack,
      small bowel, salivary glands and parafollicular cells of the thiroid gland.
      Somatostatinomas of the digestive tract appear within the pancreas and duodenum.
      Patients suffering from von Recklinghausens's disease are paticularly prone to
      the somatostatinomas of the duodenum. CASE REPORT: In this paper we presented a
      51-year-old female patient with von Recklinghausen's disease in whom, during the
      investigation for obstructive jaundice, tumor of the Vater's papilla was found.
      The patient was submitted to Whipple's duodenopancreatectomy. Histology and
      immunohistochemistry discovered type B glandular carcinoid tumor with strong
      antisomatostatin and mild antigastrin immunoreactivity. The patient stayed
      symptom-free more than four years now. CONCLUSION: Patients with von
      Recklinghausen's disease should be examined for other tumors, particularly
      carcinoids of the duodenum and papilla, especially if the signs of cholestasis
      are present.

PMID- 17438970
TI  - [Comorbidity of eating disorder and alcohol dependency].
AB  - INTRODUCTION: Epidemiological studies suggest that a high prevalence of alcohol
      addiction exists in female patients diagnosed with eating disorder in comparison
      to general population. For the purpose of explanation of the relationship of
      these disorders many conceptual models have been proposed. CASE REPORT: We
      presented a female patient displaying a comorbidity of eating disorder and
      alcohol dependency. We analyzed phenomenological similarities, personal
      characteristics and bio-psychological predisposition in order to ensure better
      understanding of the nature of the correlation of the two mentioned disorders.
      CONCLUSION: Even though, these days we find the synonym for eating disorders in
      the phrase "food addiction", it is impossible to categorize such a complex group
      of disorders to an addictive process. Moreover, we could assume that there exists
      a common psychobiological vulnerability which predisposes the development of one
      and/or the other disorder. To date knowledge has a significant implication for
      the development of new strategy in treating this comorbidity.

PMID- 17438971
TI  - [How the present Military Medical Academy was founded].

PMID- 17438972
TI  - [Prevalence, incidence, mortality, letality, morbidity].

PMID- 17438980
TI  - [Management of schizophrenia].

PMID- 17438981
TI  - [Clinical aspects of schizophrenia].

PMID- 17438982
TI  - [Gestalt therapy as possible care choice].

PMID- 17438983
TI  - [From the schizophrenic patient to the nurse's being, reflection on the
      protocols!].

PMID- 17438984
TI  - [Care trajectory and psychoses].

PMID- 17438985
TI  - [Care propositions for schizophrenia, a long history].

PMID- 17438987
TI  - [Management of schizophrenia].

PMID- 17438986
TI  - [Psycho-education for families of schizophrenic patients].

PMID- 17438988
TI  - [Nursing interview, challenges in a new mental health practice].

PMID- 17438989
TI  - [Isolation room and physical restraint].

PMID- 17438990
TI  - Georgia hospital hit by F3 tornado--all patients evacuated through the ED.
AB  - When an F3 tornado severely damaged a hospital in Americus, GA, all patients had
      to be evacuated through the emergency department. Fifty-three patients were
      evacuated by area ambulances and a school bus to other hospitals in the region.
      The hospital advises others to have an internal evacuation plan as well as two
      way radios, a megaphone to direct staff and volunteers, and additional security.
      A temporary treatment area was set up at a local church.

PMID- 17438991
TI  - How to set up emergency treatment area at a church.

PMID- 17438992
TI  - OSHA pandemic guidance reinforces need to plan.
AB  - As the new guidance from the Occupational Safety and Health Administration (OSHA)
      points out, there are practical steps you can take to protect your staff and to
      prepare for the inevitable increased absenteeism should a pandemic occur. Cross
      train staff in three or four functions so they can fill in for others if needed.
      Encourage employees who are sick to stay home, to reduce the likelihood of
      spreading disease and to combat employees coming to work when they are not at
      their best. By reassuring staff they will be safe if they report to work, you can
      keep attendance numbers as high as possible.

PMID- 17438993
TI  - If pandemic strikes, how much staff will you have?
AB  - A survey of your staff can give you insight into the reasons why they would not
      come to work during a pandemic and point to new strategies that might encourage
      them to come to work. Ask them to prioritize their reasons for staying home,
      ranking them from one to 10. Keep the responses anonymous, which will encourage
      your staff to respond to the questions honestly. Make it possible for staff
      members who opt to stay home to still work by manning the call-in center.

PMID- 17438994
TI  - Age can make a difference in patient satisfaction.
AB  - A survey demonstrates that not all patients will perceive the care they receive
      in the same manner. Learning facts like these about your customers will help you
      improve your patient satisfaction efforts. Young adult patients are the least
      likely to be satisfied and do not understand the necessity of long waits.
      Building loyalty with younger patients can pay dividends for years to come.
      Breaking down satisfaction survey data into subpopulations can help point out the
      areas in which you need to improve.

PMID- 17438995
TI  - Boundaries. Remembering who we are.

PMID- 17438996
TI  - A perfect fit. Help vendors and manufacturers help you.

PMID- 17438997
TI  - It's not the pulse. Heart rate and the ability to pump blood.

PMID- 17438998
TI  - Preventing blogorrhea. Can you control employees' Internet activity?

PMID- 17438999
TI  - Multimillion mistakes. A study finds $402 million in Medicare overpayments to the
      ambulance industry.

PMID- 17439000
TI  - Distant early ECG warning.

PMID- 17439001
TI  - Out-of-hospital STEMI alert.

PMID- 17439002
TI  - Cold care.

PMID- 17439003
TI  - Beyond the basics: vascular emergencies.

PMID- 17439004
TI  - Recognition & treatment of foot injuries.
AB  - Traumatic foot injuries can be isolated; however, they often occur in conjunction
      with other injuries. Recognizing the mechanism of injury will aid you in
      predicting foot-injury patterns. Thorough foot examination will help identify the
      injury. Proper immobilization and treatment are essential to long-term recovery.

PMID- 17439005
TI  - Coping with violent people: a multi-part series.

PMID- 17439006
TI  - Tips leadership. Little white lies: is a lie always a lie?

PMID- 17439007
TI  - Evaluation of Daphne genkwa diterpenes: fingerprint and quantitative analysis by
      high performance liquid chromatography.
AB  - Daphne genkwa contains a novel class of anticancer diterpene esters that inhibit
      DNA topoisomerase I. Fingerprint and quantitative analysis by HPLC were performed
      in order to characterise and evaluate D. genkwa. A standard fingerprint of Daphne
      diterpene esters from the root extract was first established by HPLC-UV, and the
      major peaks in the fingerprint profile were preliminarily determined using HPLC
      MS. The principal Daphne diterpene esters, yuanhuacine (1), yuanhuadine (2),
      yuanhuajine (3) and yuanhuagine (4), were isolated and identified using a
      combination of UV, IR, MS, 1H-NMR and 13C-NMR spectral data. Quantitative
      analysis indicated that 1 was the principal component in the root, and that 2 was
      the major component in the buds. The average extraction rates of 1 and 2 were
      0.0151 and 0.0033% (n=10) from the root, respectively, and 0.0020 and 0.0078%
      (n=3) from the buds, respectively.

PMID- 17439008
TI  - Comparison of the capabilities of accelerated solvent extraction and sonication
      as extraction techniques for the quantification of kavalactones in Piper
      methysticum (Kava) roots by high performance liquid chromatography with ultra
      violet detection.
AB  - A conventional extraction technique of sonication has been compared, in terms of
      extraction efficiency, extraction time and amount of solvent, with the more novel
      technique of accelerated solvent extraction for the extraction of kavain from the
      powdered roots of Piper methysticum (Kava) with acetone. The extracts were
      analysed using high-performance liquid chromatography with ultra violet
      detection. The effects of varying solvent volume and extraction time upon the
      quantity of kavain extracted with sonication, and the effects of varying
      temperature upon the kavain extraction efficiency by ASE, were investigated. ASE
      was found to be more efficient with respect to time and solvent volume required;
      however, a good agreement was found between the kavain concentration obtained
      using both extraction techniques.

PMID- 17439009
TI  - Enhanced solvent extraction of polar lipids associated with rubber particles from
      Hevea brasiliensis.
AB  - Biochemical studies of lipids bound to rubber particles have been complicated due
      to the solubility of polyisoprene chains in most extracting solvents and the
      rather delicate nature of polar lipids that are often denatured when traditional
      solvent extraction techniques are employed. In this paper, we describe a
      traditional technique and accompanying solvents that permit optimal extraction of
      rubber particle bound lipids. The technique, which is validated after
      characterizing the lipid extracts by elemental analysis, silica column adsorption
      and thin layer chromatography, appeared more suitable for extracting total lipids
      with optimal glycolipid and phospholipid contents. This technique is proposed as
      an alternative to traditional extraction methods used for solid natural rubber as
      it offers advantages with respect to ease of application, extract quality,
      extraction yields and reproducibility.

PMID- 17439010
TI  - A comparative study of multilayer perceptron neural networks for the
      identification of rhubarb samples.
AB  - Artificial neural networks have gained much attention in recent years as fast and
      flexible methods for quality control in traditional medicine. Near-infrared (NIR)
      spectroscopy has become an accepted method for the qualitative and quantitative
      analyses of traditional Chinese medicine since it is simple, rapid, and non
      destructive. The present paper describes a method by which to discriminate
      official and unofficial rhubarb samples using three layer perceptron neural
      networks applied to NIR data. Multilayer perceptron neural networks were trained
      with back propagation, delta-bar-delta and quick propagation algorithms. Results
      obtained using these methods were all satisfactory, but the best outcomes were
      obtained with the delta-bar-delta algorithm.

PMID- 17439011
TI  - Preparative isolation and purification of geniposide from gardenia fruits by
      centrifugal partition chromatography.
AB  - The iridoid glycoside, geniposide was purified by centrifugal partition
      chromatography (CPC) with a two-phase solvent system composed of ethyl
      acetate:isopropanol:water (3:2:5, v/v) from an 80% methanolic extract of fruits
      of Gardenia jasminoides. Preparative CPC yielded 56.2 mg of geniposide in a one
      step separation of 500 mg of extract, with a purity of 95% as determined by HPLC.
      Isolated geniposide was identified from its 1H-NMR, 13C-NMR and MS spectra.

PMID- 17439013
TI  - A new method for the authentication of plant samples by analyzing fingerprint
      chromatograms.
AB  - Chemical analysis by high-performance liquid chromatography or capillary
      electrophoresis of plant pulverized samples, juices or extracts is an excellent
      method for the authentication of medicinal plant species and their products,
      particularly when morphological authentication is not possible. In the
      conventional procedure, chromatograms are integrated and the heights or areas of
      several peaks are used in a supervised pattern recognition method to confirm the
      authenticity of the product. We propose a new section approach in analysing
      chromatograms, where chromatograms are split into sections, which are described
      by four variables (number of peaks in the section, average retention time of
      peaks in the section, total area of peaks in the section and average area of
      peaks in the section), and these variables are then used in statistical analysis.
      The method is especially useful when the peaks on the chromatogram are not well
      separated and it is not easy to link individual peaks on one chromatogram with
      corresponding peaks on other chromatograms. In comparison with the standard
      procedure, our approach in analyzing chromatographic data of willow-herb
      (Epilobium and Chamaenerion spp.) extracts was more objective, gave better
      results and was also easier to perform.

PMID- 17439012
TI  - HPLC-photodiode array detection analysis of curcuminoids in Curcuma species
      indigenous to Indonesia.
AB  - An optimized HPLC method with photodiode array detection was developed and
      applied to analyse the curcuminoids curcumin, demethoxycurcumin, and bis
      demethoxycurcumin in rhizomes of Curcuma mangga Val &. v. Zijp, C. heyneana Val.
      & v. Zijp, C. aeruginosa Roxb. and C. soloensis Val. (Zingiberaceae), indigenous
      to Indonesia. The method was validated with an isocratic system, a short run time
      of 10 min and a baseline separation. The curcuminoid content was 0.18-0.47% for
      C. mangga, 0.98-3.21% for C. heyneana, 0.02-0.03% for C. aeruginosa and 0.40% for
      C. soloensis.

PMID- 17439014
TI  - Steroidal constituents of rice (Rryza sativa) hulls with algicidal and herbicidal
      activity against blue-green algae and duckweed.
AB  - Two new compounds, 14-methyl stigmast-9(11)-en-3alpha-ol-3beta-D-glucopyranoside
      (1) and cholest-11-en-3beta, 6beta, 7alpha, 22beta-tetraol-24-one-3beta
      palmitoleate (2), along with the known compound beta-sitosteryl-3beta-D
      glucopyranosyl-6'-linoleiate (3), were isolated from the methanolic extract of
      rice (Oryza sativa) hulls. The structures of the two new compounds were
      elucidated using one- and two-dimensional NMR in combination with IR, EI/MS,
      FAB/MS, HR-EI/MS and HR-FAB/MS. In bioassays with blue-green algae, Microcystis
      aeruginosa UTEX 2388 and duckweed, Lemna paucicostata Hegelm 381, the efficacy of
      bioactivity of the two new compounds linearly increased as the concentration
      increased from 0.3 to 300 IgM. Compared with momilactone A, compounds 1 and 2
      showed similar and higher inhibitory activities against the growth of M.
      aeruginosa at a concentration of 300 microM. However, compound 2 was similar to
      momilactone A in inhibiting L. paucicostata growth at a concentration of 300
      microM. As a result, compound 2 appears to have a strong potential for the
      environmentally friendly control of weed and algae that are harmful to water
      logged rice.

PMID- 17439015
TI  - Application of atmospheric pressure chemical ionisation mass spectrometry in the
      identification and differentiation of Panax species.
AB  - An HPLC-MS method using an atmospheric pressure chemical ionisation (APCI) source
      has been developed to assist in the differentiation of three ginseng species:
      Panax quinquefolium (American ginseng), P. ginseng (Chinese ginseng) and P.
      notoginseng (sanqi) species. The differentiation method relies on the
      identification of ginsenosides Rf and F11 and notoginsenoside R1. R1 is observed
      in both P. notoginseng and Chinese ginseng, whilst F1, is found exclusively in
      the American species. The presence of these compounds permits the definitive
      identification of the species to be made. The APCI ionisation source has been
      employed to tackle the matrix interference in analysing Chinese medicinal
      materials and to minimise the associated matrix effects that are commonly
      encountered with other ionisation modes. Moreover, the method allows direct
      interface to conventional HPLC systems. More importantly, chemical reference
      standards of ginsenosides are not required in this method. This technique
      provides an alternative approach to analysing high molecular weight polar
      compounds that typically encountered in complex matrices of Chinese medicinal
      materials.

PMID- 17439016
TI  - Demonstration of long-chain n-alkyl caffeates and delta7-steryl glucosides in the
      bark of Acacia species by gas chromatography-mass spectrometry.
AB  - The GC-MS identification of several abundant long-chain aliphatic n-alkyl
      caffeates, together with other phydroxycinnamic acid esters, in the
      dichloromethane extracts of the bark of Acacia dealbata and A. melanoxylon, is
      reported. In addition, the unambiguous differentiation between two delta7-steryl
      glucosides (namely, spinasteryl glucoside and dihydrospinasteryl glucosides) and
      the homologous delta5-steryl glucosides was achieved based on the EI-MS
      fragmentation features of their trimethylsilyl derivatives.

PMID- 17439017
TI  - Quantification of nepetalactones in catnip (Nepeta cataria L.) by HPLC coupled
      with ultraviolet and mass spectrometric detection.
AB  - Nepetalactones, the major chemical components of catnip (Nepeta cataria L.), were
      analysed by reversed-phase HPLC coupled with UV and MS detection. Two major
      nepetalactones, Z,E-nepetalactone and E,Z-nepetalactone, were successfully
      identified and quantified. The linearity range for Z,E-nepetalactone was
      determined as 0.00655-0.655 mg/mL with a correlation coefficient of 0.9999, and
      the linearity range of E,Z-nepetalactone was found to be 0.00228-0.456 mg/mL with
      a correlation coefficient of 0.9999, under UV detection at 228 nm. The linearity
      ranges were from 0.00164 to 0.0328 mg/mL, with a correlation coefficient of
      0.9999, for ZE-nepetalactone and 0.00114-0.0228 mg/mL, with a correlation
      coefficient of 0.9999, for E,Z-nepetalactone by MS detection with selected ion
      monitoring of ion peak m/z 167. The MS detection was found to be more sensitive
      than UV detection and this method was validated as simple, reliable and sensitive
      for catnip nepetalactone analysis. This method can be used for identification and
      fingerprinting of catnip products.

PMID- 17439019
TI  - Current awareness in phytochemical analysis.

PMID- 17439018
TI  - A single HPLC-PAD-APCI/MS method for the quantitative comparison of phenolic
      compounds found in leaf, stem, root and fruit extracts of Vaccinium
      angustifolium.
AB  - A method was developed for the analysis of Vaccinium angustifolium Ait. (Lowbush
      blueberry), which is a widely used natural health product, particularly for the
      treatment of diabetic symptoms. While the anthocyanin content of the fruit has
      been well characterized, the chemistry of the vegetative parts used in supportive
      therapy for diabetes has been largely ignored. Using a metabolomics-based
      approach for compound identification with an emphasis on phenolic metabolites, a
      single HPLC-PAD-APCI/ MS method was developed for the separation and quantitation
      of the major metabolites found in the 95% ethanol extracts of leaf, stem, root
      and fruit. The leaf extract contained high concentrations of chlorogenic acid
      (approximately 100 microg/mg extract) and a variety of quercetin glycosides that
      were also detected in the fruit and stem extracts. Flavan-3-ol monomers (+)
      catechin and (-)-epicatechin were found in all plant parts but their procyanidin
      dimers were exclusively identified in the stem and root. The accuracy and
      precision of the presented method were corroborated by low intra- and inter-day
      variations in quantitative results in all plant part extracts. Further validation
      of the extraction and analytical protocols focused on identified compounds with
      reputed anti-diabetic activity, revealing recoveries greater than 80% and
      detection limits of 0.12-2.73 microg/mL.

PMID- 17439020
TI  - Current applications of the intraoperative parathyroid hormone assay in
      parathyroid surgery.
AB  - Parathyroid hormone measurement using a two-site immunochemiluminometric assay
      has allowed for a rapid and accurate technique that has found its way into the
      operative armamentarium of some parathyroid surgeons. It can be used to assess
      the completeness of parathyroid gland resection and allow for a minimally
      invasive parathyroidectomy. This operative approach has become a popular
      marketing tool, providing patients with confidence in their surgical outcome. The
      purpose of this review is to provide the surgeon with the practical points and
      pitfalls of the use of intraoperative parathyroid hormone in the treatment of
      parathyroid disease.

PMID- 17439021
TI  - The friendship and letters of Alfred Blalock and Tinsley Harrison.

PMID- 17439022
TI  - The value of scoring achalasia: a comparison of current systems and the impact on
      treatment--the surgeon's viewpoint.
AB  - Heller myotomy in patients with achalasia promises better long-term success than
      pneumatic dilation, especially in younger patients, and therefore has evolved as
      the primary treatment option. The aim of this study was to evaluate the impact of
      different disease-specific severity scores on achalasia treatment. Fifty
      consecutive patients undergoing pneumatic dilation (n = 25) or myotomy (n = 25)
      were assessed pre- and postinterventionally by clinical evaluation using the
      Eckardt Score, the Vantrappen Classification, and the Adams's Stages, as well as
      by radiologic and manometric studies and by subjective evaluation. The Eckardt
      Score and the Vantrappen Classification correlated significantly with each other.
      The Eckardt Score, because of its widest range and interval-level measurement
      properties converting the score to the Eckardt Stages, tends toward being the
      most useful system for clinical practice. The indication for myotomy or dilation
      therapy can not be set by a specific cut-off point in any system and remains an
      individual decision, including the aspects of the patient's age and failed prior
      options.

PMID- 17439023
TI  - Complications of thyroidectomy and parathyroidectomy in the rural community
      hospital setting.
AB  - The objective of this study was to examine the complications encountered in a
      series of 150 consecutive thyroid and parathyroid procedures performed by a
      single surgeon in a rural community hospital setting. The goal was to demonstrate
      that these procedures may be performed safely and with outcomes equivalent to
      those of academic hospitals in major metropolitan areas despite the lack of
      availability of specific technologies that are being increasingly used for these
      procedures in tertiary care settings. Specifically, these include intraoperative
      parathyroid hormone measurements, intraoperative recurrent laryngeal nerve
      monitoring, and the use of the gamma probe for detection of parathyroid adenoma.
      A retrospective chart review was conducted on a series of 150 patients undergoing
      any thyroid or parathyroid operation by a single surgeon in a rural setting over
      a 4-year period. Data was reported regarding success at achieving the goal of the
      operation and any perioperative complications such as recurrent laryngeal nerve
      injury, permanent hypoparathyroidism, wound hematoma, infection, or pneumonia.
      One hundred thirty-one thyroid procedures were performed (71 lobectomies, 60
      total or near total procedures) for a diverse range of patholological conditions:
      multinodular goiter, 76 (50.7%) patients, follicular adenoma, 9 (6.0%) patients,
      Hashimoto's thyroiditis, 13 (8.7%) patients, papillary carcinoma, 14 (9.3%)
      patients, follicular carcinoma, 5 (3.3%) patients, follicular variant of
      papillary carcinoma, 13 (8.7%) patients, and medullary carcinoma, 1 (0.7%)
      patient. Nineteen successful parathyroid explorations were performed for primary
      hyperparathyroidism. The overall incidence of recurrent nerve injury was 1.33 per
      cent overall (0.99% for each nerve encountered). The incidence of transient
      postoperative hypocalcemia was 13 per cent, with one patient suffering permanent
      hypoparathyroidism (0.8%). Two patients developed wound hematomas requiring
      evacuation. The overall complication rate with respect to recurrent laryngeal
      nerve injury and permanent hypoparathyroidism was consistent with or below that
      that in recent large series, despite the absence of specialized equipment for
      nerve monitoring. The success of identifying parathyroid adenoma was 100 per
      cent, despite the absence of intraoperative parathormone assays, and the decision
      not to perform radio-guided parathyroidectomy. We conclude that outcomes and
      complications in thyroid and parathyroid surgical procedures are largely
      dependent on surgeon skill and experience, and can be performed safely in the
      community setting by an experienced general surgeon despite the absence of
      advanced technology in this setting. We encourage all surgeons to continually
      examine their operative results with all technically demanding procedures when
      deciding the composition of their individual practices.

PMID- 17439024
TI  - Relationship between initial margin status for invasive breast cancer and
      residual carcinoma after re-excision.
AB  - Little data exists addressing the relationship between initial margin status in a
      specimen from an excisional biopsy and the presence of residual carcinoma in a
      subsequent specimen from lumpectomy or mastectomy. We sought to determine the
      relationship between initial margin status and the presence of residual invasive
      cancer, and to identify any relationship to other variables. This study was a
      retrospective review of pathology reports of 582 early-stage invasive duct
      carcinomas with open excisional biopsies. The initial specimen was classified
      into one of six margin categories: multiply focally positive (n = 174), focally
      positive (n = 132), margins < 1 mm (n = 98), margins 1 to 2 mm (n = 20), margins
      > 2 mm (n = 46), and margins undetermined (n = 90). All patients had a subsequent
      definitive second procedure. Pathology reports from the second procedure revealed
      the presence of residual invasive cancer by initial margin status as follows: in
      30 per cent of the initial procedures with multiply focally positive margins, in
      22 per cent with focally positive margins, in 8 per cent, 15 per cent, and 4 per
      cent with margins of < 1 mm, 1 to 2 mm, and > 2 mm, respectively, and in 28 per
      cent with undetermined margins. Women with palpable tumors, larger tumor size,
      and positive axillary nodes were more likely to have multiply focal and focally
      positive margins. Multiply focally positive and focally positive margins had
      similar residual invasive carcinoma rates and should be re-excised. All clear
      margins were equivalent; thus, re-excision was not necessary.

PMID- 17439025
TI  - Multiple indomethacin-induced jejunal ulcerations with perforation: a case report
      with histology.
AB  - Gastric and duodenal inflammation and ulceration are well-known complications of
      nonsteroidal anti-inflammatory (NSAID) usage. However, small bowel ulceration and
      perforation secondary to NSAID use is uncommon and has rarely been reported in
      the literature. We describe a perforated jejunal ulcer that developed in a
      patient using indomethacin for treatment of ankylosing spondylitis. We performed
      a literature review of NSAID-induced small bowel injury and compared the
      histology of NSAID-related injury with more familiar causes of small bowel
      perforation.

PMID- 17439026
TI  - Lung protective ventilation strategies: have we applied them in trauma patients
      at risk for acute lung injury and acute respiratory distress syndrome?
AB  - Lung protective ventilation strategies for patients with acute lung injury (ALI)
      and acute respiratory distress syndrome (ARDS) are well documented, and many
      medical centers fail to apply these strategies in ALI/ARDS. The objective of this
      study was to determine if we apply these strategies in trauma patients at risk
      for ALI/ARDS. We undertook a retrospective review of trauma patients mechanically
      ventilated for > or = 4 days with an ICD-9 for traumatic pneumothorax,
      hemothorax, lung contusion, and/or fractured ribs admitted from May 1, 1999
      through April 30, 2000 (Group 1), the pre-ARDS Network study, and from May 1,
      2003 through April 30, 2004 (Group 2), the post-ARDS Network study. Tidal volume
      (VT)/kg admission body weight, VT/kg ideal body weight (IBW), and plateau and
      peak pressures were analyzed with respect to mortality. VT/Kg admission body
      weight and IBW were significantly reduced when comparing Group 1 with Group 2
      (9.27 to 8.03 and 11.67 to 10.04, respectively). VT/kg IBW was greater (P < 0.01)
      for patients who died in Group 1 (13.81) compared with patients who lived (10.29)
      or died (9.89) in Group 2. Peak and plateau pressures were greater (P < 0.01) in
      patients who died in Group 1 than patients who lived or died in Group 2. A strict
      ARDS Network ventilation strategy (VT < 6 mL/kg) is not followed, rather a low
      plateau/peak pressure strategy is used, which is a form of lung protective
      ventilation.

PMID- 17439027
TI  - Traumatic renal artery occlusion in a patient with a solitary kidney: case report
      of treatment with endovascular stent and review of the literature.
AB  - Renal artery occlusion after blunt trauma is a rare occurrence, and the optimal
      treatment for this condition has not been established. To our knowledge,
      endovascular repair for blunt renal artery occlusion in a solitary kidney has not
      been described in the literature. This case report describes a 42-year-old woman
      with a solitary left kidney presenting with total occlusion of the left renal
      artery after a significant crush injury. She was successfully treated by
      percutaneous placement of an endovascular stent. Postprocedure, the patient
      developed acute renal failure requiring temporary dialysis. At follow-up 4 months
      later, the patient has normal urinary output and a normal creatinine.

PMID- 17439028
TI  - An appraisal of trauma in the elderly.
AB  - To review the trends of trauma in the elderly experienced at our trauma center
      compared with other Level I trauma centers. This was a retrospective trauma
      registry analysis (1996-2003) of 2783 blunt trauma in elderly (BTE) and 4568
      adult (BTA) patients in a Level 1 trauma center. Falls and motor vehicular
      crashes were the most common mechanisms noted in 47 per cent and 31 per cent (84%
      and 13% in BTE, 25% and 42% in BTA). BTE were sicker, with higher Injury Severity
      Scores (ISS), lengths of stay, and mortality (5% vs 2%, P value < 0.05). ISS was
      5.2-fold higher in nonsurvivors to survivors in BTA and 2.4-fold in BTE.
      Elevation in ISS resulted in higher linear increase in mortality in BTE (vs BTA)
      at any ISS level. Mortality in patients with ISS > or = 25 was 43.5 per cent vs
      23.8 per cent. ISS > or = 50 had 31 per cent adult survivors but no elderly
      survivors. Among isolated injuries, head trauma in the elderly carried the
      highest mortality, at 12 per cent (19% in patients with an Abbreviated Injury
      Score > or = 3). Abdominal injuries were the most lethal (18.3% and 41.2% in
      patients with an Abbreviated Injury Score > or = 3) in multiple trauma victims
      (41% vs 18% in isolated trauma). There was 4.4-fold increased mortality in the
      presence of thoracic trauma. Combined head, chest, and abdominal trauma carried
      the worst prognosis. Thirty-four per cent of BTE and 88 per cent of BTA patients
      were discharged home. Elderly patients need more aggressive therapy, as they are
      sicker with higher mortality.

PMID- 17439029
TI  - Classification of lymph node metastases from gastric cancer: comparison between N
      site and N-number systems. Our experience and review of the literature.
AB  - The tumor, node, metastasis (TNM) system has become the principal method for
      assessing the extent of disease, determining prognosis in gastric cancer
      patients, and affecting the therapy strategies. The extent of lymph node
      metastasis is the most important prognostic factor. The aim of this study was to
      compare the N-classifications of the 4th and the 5th-6th TNM editions and to
      evaluate retrospectively the prognostic value of the 2002 TNM edition. We
      evaluated 344 patients who underwent curative total or subtotal gastrectomy.
      Nodal involvement was detected in 221 (64%) patients. Median follow-up period was
      76 months. Thirty per cent of the old N1 patients were reclassified as pN2
      (18.5%) and pN3 (11.3%). Eighty-eight per cent of the old N2 patients were
      reclassified as pN1 (75%) and pN3 (13.7%). In reclassifying the patients,
      statistically significant changes were reported between 1987 and 2002 TNM stage
      grouping, mainly in stage IIIB and IV. The 5-year survival rate per stage group
      did not statistically differ between the 4th and the 5th-6th editions, although a
      diminutive trend was registered in the IIIA stage. pTNM stage, nodal numerical
      stage, nodal topographical stage, and depth of tumor invasion resulted in
      significantly independent prognostic factors. Our data confirm the simplicity and
      easy application of the new stadiation and the better prognostic stratification
      of the N-stage. The pN3 group showed a worse prognosis independent of location.
      On the other hand, prognostic value of pN1 and pN2 stage is lower, probably
      depending on lymph node location. In multivariate analysis, the difference
      between old and new TNM staging is low. Hence, we suggest comparing lymph node
      location and number in larger series. In our series, in pT1 tumors, neither pN2
      nor pN3 involvement was found. Hence, in our opinion, for correct N-staging, 10
      lymph nodes in early gastric cancer and at least 16 in the other pT-stages seem
      sufficient for a real pN0 stadiation.

PMID- 17439030
TI  - Anterior mediastinal herniation of the transverse colon after an omental flap
      transposition.
AB  - Poststernotomy mediastinitis continues to be an infrequent but serious
      complication after cardiac surgery. We present a case of a 59-year-old man who
      developed a deep sternal wound infection after an emergency cardiac surgery.
      Omental transposition flap was used to cover the sternal defect. Several days
      later, the patient developed a transverse colon herniation into the anterior
      mediastinum that required emergency exploration and colon resection. The patient
      survived after a difficult hospital course. Indications, technical points, and
      possible complications of using omental flap transposition are discussed.

PMID- 17439031
TI  - The contribution of acute cholecystitis, obesity, and previous abdominal surgery
      on the outcome of laparoscopic cholecystectomy.
AB  - The aim of this study was to evaluate the impact of acute cholecystitis (AC),
      obesity, and previous abdominal surgery on laparoscopic cholecystectomy (LC)
      outcomes. Records of 1940 patients undergoing LC in 1992 and 2004 were reviewed
      in order to assess the independent and joint effects of the above risk factors on
      conversion, morbidity, operation time, and hospital stay. In multivariate
      regression analysis, adjusting for sex and age, AC alone and in combination with
      obesity or previous abdominal surgery increased the risk of conversion and
      complications and was associated with prolonged operation time and hospital stay
      compared with the patients without any of the risk factors (reference group). The
      independent and joint effects of obesity and previous abdominal surgery were
      significant only on operation time. On the contrary, previous upper abdominal
      surgery alone and in combination with AC was associated with 3- and 17-fold
      relative odds of conversion, respectively. The combined presence of AC, obesity,
      and previous abdominal surgery yielded an odds ratio for conversion of 7.5 and
      for complications of 10.7, as well as a longer operation time and hospital stay.
      The presence of previous upper abdominal surgery with AC and obesity had a
      substantial effect on conversion, with an odds ratio of 87.1 compared with the
      reference group. LC is safe in patients with AC, previous abdominal surgery, or
      obesity. However, the presence of inflammation alone or in combination with
      obesity and/or previous (especially upper) abdominal surgery is the main factor
      that influences the adverse outcomes of LC.

PMID- 17439032
TI  - Nephron-sparing radical excision of a giant perirenal liposarcoma involving a
      solitary kidney.
AB  - We describe our experience in a patient with a congenital solitary kidney encased
      by a perirenal liposarcoma managed by nephron-sparing excision. The best
      predictor of survival with liposarcoma is complete resection of the tumor.
      Generally a diffuse peri-renal liposarcoma arising within Gerota's fascia would
      necessitate a radical nephrectomy. Having a congenitally solitary kidney, this
      patient refused nephrectomy, therefore a kidney-sparing excision of his
      liposarcoma was attempted. To obtain negative margins and to provide a nephron
      sparing excision, the capsule of the kidney was resected with the mass. Direct
      extension into the diaphragm necessitated an en bloc resection of 4 x 6 cm of the
      left hemidiaphragm. The defect was reconstructed with a Gortex patch graft.
      Pathology revealed a 32 x 22 x 8-cm liposarcoma with areas of sclerosing
      liposarcoma and poorly differentiated spindle cell sarcoma, focally Grade 3 of 3,
      with the remaining tumor being Grade 1. There was diaphragmatic invasion, but all
      surgical margins were negative. At 22 months CT follow-up, the patient has no
      radiographic evidence of disease. Excision of this mass with the renal capsule
      allowed our patient to be margin negative and maintain normal renal function.
      This is the only report in the literature describing nephron-sparing resection of
      a giant perirenal liposarcoma involving a solitary kidney.

PMID- 17439033
TI  - Total pulmonectomy in trauma: a still unresolved problem--our experience and
      review of the literature.
AB  - Emergency pneumonectomy for trauma is associated with very high mortality.
      Despite significant improvement of the intensive care resources, results of this
      procedure have not been improved during the last 20 years. When performed because
      of hemorrhagic shock, pneumonectomy is almost always fatal. We present a series
      of four patients who underwent total pneumonectomy in our trauma center. The main
      purpose of this study was to describe pathophysiologic changes and to discuss
      possible therapeutic alternatives based on the literature review after this
      operation.

PMID- 17439034
TI  - Delayed neurologic deficit after infrarenal endovascular aortic aneurysm repair.
AB  - Spinal cord ischemia is a rare and devastating complication after elective
      abdominal aortic aneurysm repair. It has recently been reported to occur after
      endovascular aortic aneurysm repair. We report the first case of delayed
      neurologic deficit after endovascular aortic aneurysm repair using the Zenith
      (Cook) device.

PMID- 17439035
TI  - Minimally invasive procedures for diagnosis of traumatic right diaphragmatic
      tears: a method for correct diagnosis in selected patients.
AB  - Traumatic rupture of the diaphragm is no longer uncommon. Because of the
      increasing frequency of motor vehicle accidents, the rate of blunt trauma to the
      chest and abdomen, which are the most common causes of diaphragmatic rupture, is
      increased as well. However, the diagnosis is frequently missed or delayed because
      of the lack of sensitivity and specificity of imaging modalities. Diagnostic
      laparoscopy is considered a standard tool for penetrating injuries to the left
      diaphragm and is widely practiced in selected cases. Right diaphragmatic tears,
      however, are more difficult to diagnose because of the sealing effect of the
      liver. Blunt abdominal trauma can cause large right diaphragmatic tears, causing
      liver incarcerations and respiratory compromise, therefore demanding the need for
      a comparable diagnostic tool. A high index of suspicion, together with knowledge
      of the mechanism of trauma, is the key factor for the correct diagnosis. Once the
      diagnosis has been considered, diagnostic laparoscopy and/or diagnostic
      thoracoscopy should be performed to confirm or rule out this injury. Factors
      suggestive of a right diaphragmatic tear include newly or progressive elevation
      of the right diaphragm and respiratory distress without underlining lung injury.
      The timing of the procedure should be in accordance with the hemodynamic and
      respiratory status of the patient. This procedure should be performed
      semielectively if there are no other indications for surgical intervention.

PMID- 17439036
TI  - Splenic rupture: an unusual complication of colonoscopy.
AB  - Splenic injury is a known, albeit rare, complication of diagnostic and
      therapeutic colonoscopy. Within a 6-month period, we observed two colonoscopic
      splenic injuries. We report these two cases of splenic injury who presented
      differently after colonoscopy: one presented as frank hemorrhagic shock, and the
      other as a subacute splenic hemorrhage with symptomatic anemia. The first patient
      presented with hemorrhagic shock several hours after a diagnostic colonoscopy and
      required an emergency splenectomy. The second patient presented with symptomatic
      anemia several days after a diagnostic colonoscopy and was treated by
      angiographic embolization. Clinical presentation and discussion of the mechanisms
      of injury, available treatment options, and strategies for preventing
      colonoscopic splenic injuries are presented. Awareness of this complication is
      paramount in early recognition and management of this potentially life
      threatening injury.

PMID- 17439037
TI  - Poorly differentiated carcinoma arising in a Warthin's tumor of the parotid
      gland: pathogenesis, histopathology, and surgical management of malignant
      Warthin's tumors.
AB  - Warthin's tumor is a benign lymphoepithelial neoplasm representing 10 per cent of
      all parotid gland tumors. Malignant transformation of a Warthin's tumor is an
      extremely rare event. We report a case of a patient with poorly differentiated
      carcinoma arising from a Warthin's tumor, as well as review the pathogenesis,
      histopathology, and surgical management of malignant Warthin's tumors.

PMID- 17439038
TI  - Ischemic colitis: an uncommon manifestation of pheochromocytoma.
AB  - Pheochromocytoma are rare neuroectodermal tumors, responsible for less than 1 per
      cent of cases of hypertension. The protean manifestations of pheochromocytomas
      arise from the effects of catecholamine hypersecretion upon alpha and beta
      receptors. The lesion may infrequently present with gastrointestinal complaints
      ranging from constipation and nausea to megacolon and ischemic colitis. Ischemic
      colitis in association with pheochromocytoma occurs from intense splanchnic
      vasoconstriction. A case of pheochromocytoma presenting as ischemic colitis is
      reported.

PMID- 17439039
TI  - Mesenteric venous thrombophlebitis--septic thrombophlebitis of the inferior
      mesenteric vein: an unusual manifestation of diverticulitis.
AB  - We report a case of a 57-year-old female patient who presented with fever,
      abdominal pain, and bacteremia. A CT scan demonstrated sigmoid diverticulitis and
      air within the inferior mesenteric vein. The patient underwent exploratory
      laparotomy and sigmoid colectomy. She was discharged without complications.
      Septic thrombophlebitis of the inferior mesenteric vein is a rare complication of
      diverticulitis. It may manifest as bacteremia not responding to intravenous
      antibiotics. CT scan findings are diagnostic, and include evidence of
      intraluminal gas within the inferior mesenteric vein. As with any case of
      complicated diverticulitis, the treatment is surgical resection of the involved
      colon.

PMID- 17439040
TI  - Recurrent metachronous metastatic multifocal renal cell carcinoma to the
      pancreas.
AB  - Renal cell carcinoma (RCC) metastatic to the pancreas may present synchronously
      or years after the initial diagnosis. In the absence of more widespread disease,
      surgical extirpation is recommended and is often associated with long-term
      survival. Most patients present with isolated metastases, with the vast majority
      of the literature pertaining to this select group. Multifocal metastases and
      recurrent metastatic disease after previous surgical resection of the pancreas
      for RCC have been less well described. Most often, surgery has been performed in
      these latter populations, although data with respect to long-term survival
      remains incomplete. Despite the use of routine CT, multifocal disease is often
      discovered unexpectedly at the time of surgical exploration or on final
      pathologic analysis, and diagnostic strategies to improve recognition of this
      entity have been incompletely assessed. Management of recurrent metastatic and
      multifocal RCC to the pancreas within the context of the existing literature is
      suggested.

PMID- 17439041
TI  - The use of spray electrocautery to control presacral bleeding: a report of four
      cases.
AB  - Bleeding originating from the presacral venous plexus during pelvic operations is
      difficult to control, constituting a potentially life-threatening complication.
      Although suture ligatures, packing, and placement of tacks are established
      hemostatic techniques, they are often proved to be ineffective. We report a
      simple novel technique using spray diathermy for managing this severe
      complication. We have applied our method in four patients, two undergoing low
      anterior resection, and the others undergoing abdominoperineal resection for
      rectal cancer, that manifested severe presacral bleeding during rectal
      mobilization. Electrocautery at spray setting was applied slightly above the
      target bleeders at the presacral fascia, delivering a high-frequency electrical
      current in combination with drainage suction. In all cases, the method resulted
      in successful hemostasis. Applying spray electrocautery is a simple and effective
      method for controlling presacral bleeding. The advantages of using such a method
      instead of conventional hemostatic techniques include the option of varying the
      degree of haemostatic effect by altering the frequency and the volume of electric
      current.

PMID- 17439042
TI  - Colorectal lymphangioma.
AB  - Lymphangiomas of the colon are historically rare benign tumors. Only 331 cases
      have been reported in the world medical literature between 1931 and 2004. With
      widespread use of colonoscopy, however, they are being found more frequently. We
      report the case of a 74-year-old woman in whom a colonoscopy revealed a 3 x 4-cm
      submucosal lesion in the cecum that was eventually diagnosed as a lymphangioma. A
      CT of the abdomen showed a soft-tissue mass in the cecum and a low-density
      hepatic lesion. An endoscopic ultrasound of the colon showed a 3 x 4-cm
      hypoechoic lesion with internal septa arising from the submucosal layer of the
      cecum. This lesion resembled a vascular malformation; therefore a biopsy specimen
      was not taken. Pathologic findings of a specimen taken after a subsequent right
      hemicolectomy identified a submucosal lymphangioma. Published reports indicate
      that colonoscopy cures most lesions smaller than 2.5 cm in diameter. Resection
      should be reserved for larger lesions or those in patients exhibiting protein
      losing enteropathy.

PMID- 17439043
TI  - An atypical computed tomographic finding of colonic lipoma.

PMID- 17439044
TI  - Compost-based waste treatments: virtuous or vicious bioprocessing?

PMID- 17439045
TI  - Assessment of municipal solid waste compost quality using standardized methods
      before preparation of plant growth media.
AB  - The quality of compost and its suitability for agricultural application depend
      upon physical and chemical parameters such as water-holding capacity, porosity,
      pH, electrical conductivity, C/N ratio, available nutrients and the absence of
      toxic substances. In the present study a complete characterization of an
      industrial municipal solid waste compost (MSWC) based on standardized European
      methods (CEN) for soil improvers and growing media was obtained, and compared
      with the quality of other Spanish composted biowaste and conventional substrates
      such as peat and pine bark. The MSWC was obtained from the main composting plant
      in Galicia (Spain), which processes organic waste that has been separated at
      origin and collected from more than 100 000 inhabitants. The MSWC presented a
      lower C/N ratio (15) than peat (84) and composted pine bark (CPB) (211), but had
      a similar ratio to other marketed MSWC. The nutrients and heavy metals were
      extracted using different recommended solvents (water, CaCl2 + diethylen triamin
      pentaacetic acid, and aqua regia). The nutrient concentrations of composted urban
      waste or manure were much higher than those of peat, CPB or pine bark. On the
      basis of the results of the plant tolerance test, the MSWC could be employed
      directly as a soil improver, but would need to be diluted with other low-salt
      components such as peat or CPB before being used as a growing media.

PMID- 17439046
TI  - Emissions from baled municipal solid waste: II. Effects of different treatments
      and baling techniques on the emission of volatile organic compounds.
AB  - This paper focuses on the volatile organic compound emissions from baled
      municipal solid waste (MSW). The analytical methodology was based on sampling
      with adsorbent tubes once a month during seven occasions within a time period of
      1 year. Automated analyses were carried out on-line work-up with thermal
      desorption directly connected to a gas chromatograph-mass spectrometer. The
      effect of different baling techniques, cylindrical and rectangular baling was
      compared. It was found that cylindrically baled MSW emitted larger concentration
      of esters than their rectangular counter parts. Conversely, aromatic compounds
      emissions dominated in rectangularly baled MSW. This indicates that different
      degradation mechanisms operate in the waste bales. Cylindrical and rectangular
      bales are generally wrapped with six layers of 250 microm thick low density
      polyethylene (LDPE). It was observed that by wrapping an extra six layers of LDPE
      film onto the bales, the emissions from cylindrical bales increased while
      emissions from the rectangular counterpart decreased. Over time, the volatile
      organic compound emissions from cylindrical bales decreased two orders of
      magnitudes from 96.2 +/- 20.8 microg m(-3) in September 2003 to 0.80 +/- 0.07
      microg m(-3) in July 2004. The rectangular bales exhibited an almost identical
      relative emission reduction from 54.4 +/- 4.3 microg m(-3) in September 2003 to
      0.46 +/- 0.02 microg m(-3) in July 2004. Future work will concentrate on full
      scale storages, taking into account waste type, storage size, temperature
      development and the different baling techniques among other variables.

PMID- 17439047
TI  - Improving the adsorption capacity and solid structure of natural volcanic soil
      using a foaming-sintering process based on recycled polyethylene terephthalate
      (PET).
AB  - The volcanic soils of southern Chile have demonstrated a high capacity to adsorb
      environmental pollutants, but for an industrial application, a stable solid
      material is necessary. The objective of this work was to produce a stable ceramic
      material through a process involving volcanic soil-polyurethane foam produced
      with recycled polyethylene terephthalate (PET)-polyols, and further thermal
      treatment. The selected foam formulation with 35.4% volcanic soil (< 63 microm)
      seems to be the most suitable for thermal treatment, with temperature steps at
      700, 850, 1000 and 1200 degrees C. The porous ceramic material obtained has a
      stable solid form and an improved chlorophenols adsorption capacity (comparable
      to natural zeolites) that makes it suitable for advanced wastewater treatment and
      landfill leachate depuration.

PMID- 17439048
TI  - Recycling of aged refuse from a closed landfill.
AB  - In this study, refuse excavated from a typical refuse landfill in Shanghai after
      8-10 years of placement was characterized in terms of particle size, total
      nitrogen, total phosphorus, and biodegradable matter. The refuse contained a
      large and diverse population of micro-organisms with a high capacity for
      decomposing refractory organic matter present in some wastewaters, including
      leachate. It was found that the aged refuse was quite stable after about a decade
      of decomposition in the warm, humid climate of southern China. The fine fractions
      resembled and had the properties of black soil, a medium that is suitable for
      green construction, organic fertilizer, or as bioreactor media for biological
      treatment of organic wastewaters. Excavation of the aged refuse would make about
      50% of the space available for fresh refuse. The plastics, glass, textiles, and
      cans can be readily mechanically separated and recycled after cleaning. It is
      estimated that at least 200 millions tonnes of such aged refuse are available in
      China alone, and at least 10 times that much is buried worldwide. Hence, the
      evaluation of mined landfill waste and consideration of its potential uses is of
      great significance.

PMID- 17439049
TI  - Optimal solid waste collection routes identified by the ant colony system
      algorithm.
AB  - In the present paper, the Ant Colony System (ACS) algorithm is used for the
      identification of optimal routes in the case of municipal solid waste (MSW)
      collection. The proposed MSW management system is based on a geo-referenced
      spatial database supported by a geographic information system (GIS). The GIS
      takes into account all the required parameters for solid waste collection. These
      parameters include static and dynamic data, such as the positions of waste bins,
      the road network and the related traffic, as well as the population density in
      the area under study. In addition, waste collection schedules, truck capacities
      and their characteristics are also taken into consideration. Spatio-temporal
      statistical analysis is used to estimate inter-relations between dynamic factors,
      like network traffic changes in residential and commercial areas. The user, in
      the proposed system, is able to define or modify all of the required dynamic
      factors for the creation of alternative initial scenarios. The objective of the
      system is to identify the most cost-effective scenario for waste collection, to
      estimate its running cost and to simulate its application. Finally, the results
      of the ACS algorithm are compared with the empirical method currently used by the
      Municipality of Athens.

PMID- 17439050
TI  - Lessons learned for a more efficient knowledge and technology transfer to South
      American countries in the fields of solid waste and contaminated sites
      management.
AB  - The present paper describes the development, performance and conclusions derived
      from three know-how and technology transfer projects to South American countries.
      The first project comprised a collaborative study by European and South American
      universities to find sustainable solutions for Chilean and Ecuadorian leather
      tanneries which had underachieving process performances. The second project
      consisted of investigations carried out in a Brazilian municipality to enhance
      its municipal solid waste management system. The final collaborative programme
      dealt with the initial identification, evaluation and registration of suspected
      contaminated sites in an industrial region of Chile. The detailed objectives,
      methods and procedures applied as well as the results and conclusions obtained in
      each of the three mentioned projects are presented, giving special attention to
      the organizational aspects and to the practical approach of each programme,
      concluding with their main advantages and disadvantages for identifying a set of
      qualitative and quantitative suggestions, and to establish transferable methods
      for future applications.

PMID- 17439051
TI  - Anaerobic digestion potential of urban organic waste: a case study in Malmo.
AB  - A study of existing organic waste types in Malmo, Sweden was performed. The
      purpose was to gather information about organic waste types in the city to be
      able to estimate the potential for anaerobic treatment in existing digesters at
      the wastewater treatment plan (WWTP). The urban organic waste types that could
      have a significant potential for anaerobic digestion amount to about 50 000
      tonnes year(-1) (sludge excluded). Some of the waste types were further evaluated
      by methane potential tests and continuous pilot-scale digestion. Single-substrate
      digestion and co-digestion of pre-treated, source-sorted organic fraction of
      municipal solid waste, wastewater sludge, sludge from grease traps and fruit and
      vegetable waste were carried out. The experiments showed that codigestion of
      grease sludge and WWTP sludge was a better way of making use of the methane
      potential in the grease trap sludge than single-substrate digestion. Another way
      of increasing the methane production in sludge digesters is to add source-sorted
      organic fraction of municipal solid waste (SSOFMSW). Adding SSOFMSW (20% of the
      total volatile solids) gave a 10-15% higher yield than could be expected by
      comparison with separate digestion of sludge respective SSOFMSW. Co-digestion of
      sludge and organic waste is beneficial not just for increasing gas production but
      also for stabilizing the digestion process. This was seen when co-digesting fruit
      and vegetable waste and sludge. When co-digested with sludge, this waste gave a
      better result than the separate digestion of fruit and vegetable waste.
      Considering single-substrate digestion, SSOFMSW is the only waste in the study
      which makes up a sufficient quantity to be suitable as the base substrate in a
      full-scale digester that is separated from the sludge digestion. The two types of
      SSOFMSW tested in the pilot-scale digestion were operated successfully at
      mesophilic temperature. By adding SSOFMSW, grease trap sludge and fruit and
      vegetables waste to sludge digesters at the wastewater treatment plant, the
      yearly energy production from methane could be expected to increase from 24 to 43
      GWh.

PMID- 17439052
TI  - Modelling C and N mineralization during decomposition of anaerobically digested
      and composted municipal solid waste.
AB  - Application of municipal solid waste (MSW) to arable land can be used to close
      the nutrient cycle between urban and rural areas. The aim of the current study
      was to quantify net N mineralization and respiration from composted MSW (CMSW)
      and anaerobically digested MSW (ADMSW) applied to soil, and to test whether a
      simple relationship between net N mineralization and respiration that was
      developed for plant materials, was applicable for these types of MSW. In a
      laboratory experiment, CMSW and ADMSW were incorporated into soil and incubated
      at 15 degrees C. During the 149-day experiment, netN mineralization and
      respiration were determined. Cumulative respiration derived from both MSW types
      was very steep during the first 30 days, after which it levelled off. However,
      calculated on the basis of applied C, the ADMSW was 10 times more degradable than
      the CMSW. Both MSW types caused initial net N immobilization followed by re
      mineralization. A simple model based on the relationship between net N
      mineralization and respiration was only applicable for the MSW after significant
      modifications. If farmers are to recognize CMSW and ADMSW as valuable
      fertilizers, it is important that they can be produced with higher maturity, in
      order to avoid initial N immobilization.

PMID- 17439053
TI  - Report: environmental assessment of Darmstadt (Germany) municipal waste
      incineration plant.
AB  - The focus of this study was the emissions from waste incineration plants using
      Darmstadt (Germany) waste incineration plant as an example. In the study the
      emissions generated by incineration of the waste were considered using three
      different approaches. Initially the emissions from the waste incineration plant
      were assessed as part of the impact of waste management systems on the
      environment by using a Municipal Solid Waste Management System (MSWMS) assessment
      tool (also called: LCA-IWM assessment tool). This was followed by a comparison
      between the optimal waste incineration process and the real situation. Finally a
      comparison was made between the emissions from the incineration plant and the
      emissions from a vehicle.

PMID- 17439054
TI  - Report: treatment of commercial, construction and demolition waste in North Rhine
      Westphalia: policy-making and operation options.
AB  - This paper summarizes a long-term-investigation of the mechanical treatment of
      commercial, construction and demolition waste materials in North Rhine-Westphalia
      in the light of applied operation standards and a disposal ban on untreated
      waste. It is shown how both the allocation of output materials from mechanical
      treatment plants and the subsequent treatment channels have changed since
      enforcement of the ban in 2005. Based on the findings of the investigation, two
      waste management scenarios offering alternative policies have been defined and
      are discussed. It is suggested that consistent enforcement of the ban affects
      both the diversion of waste to incineration and the recovery of materials on a
      regional scale. On the other hand, potential energy recovery may be fully
      exploited only insofar as operators of mechanical treatment plants concentrate
      their business on the production of refuse-derived fuel.

PMID- 17439055
TI  - Is health care ready for supply chain standards? Industry groups collaborate with
      NAHIT to identify protocols. Interview by Alan Joch.

PMID- 17439056
TI  - Things to know when choosing an MMIS.

PMID- 17439057
TI  - Using education to ensure hand hygiene compliance.

PMID- 17439058
TI  - Lower endoscope costs with repair reduction plan.

PMID- 17439059
TI  - Protect health care workers from excessive radiation.

PMID- 17439060
TI  - Troubleshooting sterilization.

PMID- 17439061
TI  - Automation, off-site warehouse save costs.

PMID- 17439062
TI  - Cardinal Health sells pharmaceutical services unit. What the transition means for
      hospitals.

PMID- 17439063
TI  - Effective policies and procedures play important role in patient safety.

PMID- 17439064
TI  - [Recent insights into the pathogenesis of abdominal symptoms in functional bowel
      disorders].
AB  - In the gut, 5-HT acts as a paracrine signalling molecule released by
      enterochromaffin cells and as a transmitter released by some descending
      serotonergic interneurons. It has a prominent role in the regulation of motility,
      vascular tone, secretion and perception both in normal and under certain
      pathophysiological conditions, such as the carcinoid syndrome and the irritable
      bowel syndrome (IBS). Serotonin is known to markedly influence bowel function by
      activating at least five receptor types (5-HT(1,2,3,4,7)). Among all 5-HT
      receptors, those belonging to the 5-HT3 (a ionotropic receptor) and 5-HT4 (a
      metabotropic receptor) type are the most extensively studied in gastroenterology,
      resulting in commercially available (although not worldwide) serotonergic agents
      for the treatment of IBS and functional dyspepsia. Recently, 5-HT7 receptors have
      been found to participate in the accommodation process of the circular muscle
      during the preparatory phase of ileal peristalsis. Since an exaggerated
      accommodation of the gut wall may contribute to abdominal distension and
      bloating, 5-HT7 receptor ligands may offer innovative opportunities for the
      pharmacological treatment of functional bowel disorders.

PMID- 17439065
TI  - [Telomerase activity: a molecular marker for early diagnosis of bladder tumor].
AB  - Quantitative evaluation of telomerase activity in voided urine represents a
      molecular test for early diagnosis of bladder tumor. This test shows a high
      accuracy, mainly in males bladder tumor, and could be an important non invasive
      diagnostic tool for bladder cancer detection in high-risk groups screening
      programs.

PMID- 17439066
TI  - [When a doctor must treat a collegue].
AB  - The literature about the physician emotional life underlined how to care a
      collegue generates stress. However this situation is not so much investigated.
      The aim of this article is to investigate the nature of the relation and of the
      physician inner life when the doctor meets a patient-doctor, by means of
      narratives and a qualitative analysis. Having a colleague as patient seems to be
      very challenging and to evocke struggling feelings difficult to handle with well
      known stategies.

PMID- 17439067
TI  - [Evaluation of the reliality of an oncotropic drug in diagnostics of the
      retrosternal lesions].
AB  - Aim of this research is the evaluation of an oncotropic drug in diagnostics of
      substernal goiter. We used the SESTA-MIBI in 26 patients with cervico-mediastinal
      goiter and evaluated the pre and intra operating data with the histopathological
      specimen. The radiodrug has noticed profit in the differential from neoplastic
      and colloidal tissue, even if in a few cases it has also demostrated affinity for
      the benign adenomas. When the fine aspirated needle biopsy has turned out
      inadwisable or not setting, the MIBI methodical has been of special help. The
      extent of the use of this radiodrug also to parathyroid and cardiac pathology has
      made the economical costs cheaper and promoted the routine use of the
      methodology.

PMID- 17439068
TI  - [Panhypopituitarism from pituitary metastases of breast cancer].
AB  - Metastases to the pituitary gland are uncommon causes of hypopituitarism, to be
      particularly considered in patients affected with disseminated cancers, arising
      in the breast or in the lung. Differential diagnosis could be correctly addressed
      by the concomitant presence of diabetes insipidus, due to the prominent
      involvement of the posterior lobe, and by some neuroradiological findings. We
      report the case of a 58-year-old woman, suffering from advanced breast cancer,
      who developed diabetes insipidus and anterior hypopituitarism. Magnetic resonance
      images showed diffuse encephalic metastatic lesions, with a thickened pituitary
      stalk, loss of high signal intensity of posterior lobe and a mildly enlarged and
      inhomogeneously enhanced adenohypophysis. Substitutive hormonal therapy was
      started, but the patient died five months later due to the progression of the
      neoplastic disease.

PMID- 17439069
TI  - [Recent advances on the role of chemokines/chemokine receptors in the
      pathogenesis of idiopathic pulmonary fibrosis].
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung
      disease characterized by fibrosis in the lung parenchyma and collagen deposition
      leading to respiratory failure. Different etiopathogenetic hypothesis have been
      formulated during the last years and many studies recently published demonstrated
      that in most of processes suggested for the onset and the development of IPF,
      chemokines and chemokine receptors are involved. Dysregulated expression of
      chemokines and their receptors during inflammatory processes might also alter the
      equilibrium between angiostatic and angiogenic processes leading to
      neovascularization in the lung tissue. Studies on chemokines/chemokine receptors
      could shed light on the mechanisms involved in IPF and draw new therapeutic
      strategies to block the progression of the disease.

PMID- 17439070
TI  - [Obesity in adolescents: physical correlated pathologies, and therapeutic state
      of art].
AB  - Obese adolescents are prone to several pathologies, which may begin in this
      period of life and have a continuity in adult age. In this review the author
      tries first to explain the obesity definition in infants, children, and
      adolescents. Some pathologies may appear in adolescent age. First of all, some
      features of the so called metabolic syndrome; furthermore, hormonal alteration
      during and after puberty, genital appearance in the obese adolescent male,
      respiratory problems as apnea, asthma, and the Pickwick syndrome. The non
      alcoholic fat liver disease is also described, and the orthopedic problems as
      well, owing to the overweight: from abnormal body posture to structural
      consequences on the skeleton. Finally, some remarks concerning pharmacological
      and surgical approach are presented.

PMID- 17439071
TI  - [Obesity and adolescence: psychological factors and family relationships].
AB  - The importance of psychological problems for children obesity and the role of the
      family context in favouring both pathology appearance and maintenance and
      eventually the failure of a correct dietetic therapy are presented. Particularly,
      maternal attitudes are underlined: obese children's mothers tend to make the
      family their exclusive centre of interest. They also tend to dedicate themselves
      to their children with possessiveness and hyper-protection. They seem to have an
      insistent requirement of idealisation of their own role as parents and reward
      expectations that confirm the efficiency of the care they provide their children.
      Moreover the psychological features of obese adolescents with anxious and
      depressive personality traits related to impulsivity and emotional immaturity are
      analysed.

PMID- 17439073
TI  - 2007 thresholds for Conditional Accreditation and Preliminary Denial of
      Accreditation.

PMID- 17439072
TI  - [Burning mouth syndrome].
AB  - Burning mouth syndrome (BMS) is characterized by burning sensations of the oral
      cavity in the absence of abnormalities of the oral mucosa. BMS predominantly
      affects middle-aged women. This condition has a multifactorial etiology. Multiple
      approaches to treatment have been described. This article examines BMS, its
      related factors, and treatment options.

PMID- 17439075
TI  - Correction: Home Care Applicability Grid.

PMID- 17439077
TI  - Correction: Standard PC.13.20, element of performance 3 for ambulatory care.

PMID- 17439078
TI  - Correction: medication management chapter for behavioral health care.

PMID- 17439079
TI  - Establish quality with data, word-of-mouth.

PMID- 17439080
TI  - Physician recruitment tactics offer docs peace of mind.

PMID- 17439081
TI  - Are retail clinics a valid business model or a passing fad?

PMID- 17439082
TI  - Strategies to aid retention, foster growth, or accomplish both.

PMID- 17439083
TI  - [An 8-year prospective follow-up study of physicians departing health care in
      Belgium (1994-2002)].
AB  - Several OECD countries have capped the number of physicians to be licensed to
      practice. However, a relevant cap must take into account changes in physician
      activities. We set out to study the transitions leading physicians to leave
      health care or to stop any activity in health system. These transitions were
      assessed using a register of medical practice. We studied changes in activity
      between 1994 and 2002 for about 19,840 physicians who in 1994 were already
      working for 5 years and were in 2002 less than 65 years old. After 8 years of
      career, one physician out of 20 were inactive in health system. Some medical
      specialties such as surgery and radiotherapy had a greater risk of leaving health
      care while GP's had a lower risk. Gender differences in leaving health system
      were mostly non-existant in younger age groups but then increased with age. Among
      physicians aged 55 and over, women were more likely to leave health system. We
      conclude that the percentage of physicians leaving health care after 5 years of
      practice is significant and deserve being taken into account for manpower
      planning and that planning should be aware of that some groups of physicians are
      more at risk than others to leave health care. Qualitative studies would help
      understand better this drop out.

PMID- 17439084
TI  - [Utilization and under-utilization of health care in Belgium and other
      countries].
AB  - Utilization of health care is a major concern in the debates about public
      expenditures and the regulation of human health resources. Concerns regarding
      inappropriate services are regularly mentioned in Belgium. Our study aims at
      assessing the utilization of health care, with a particular focus on the impact
      of morbidity, and a possible sub-consumption behaviour. The probability of having
      had a medical encounter with a general practitioner or with a specialist during
      the latest year and the probability of a frequency of encounters higher than
      national average is assessed thanks to logistic regressions. The functional
      limitations and the chronic conditions (mainly the poly-pathology) are major
      factors related to patient encounters with medical doctors. In the future, the
      number of individuals suffering from functional limitations and/or chronic
      illness will increase due to the ageing of the population. The pressure on health
      expenditures will increase also if: the frequency of encounters is adequate, as
      recommended by the "guidelines" for some illnesses and, the frequency of
      encounters increases due to the evolution of other factors that have been put
      forward by our logistic regressions. However, any sub-consumptions cannot be
      simply labeled as additional real needs, because these are also linked to some
      characteristics of the patients. Consequently, problems of subconsumption cannot
      be easily solved just by increasing medical supply.

PMID- 17439085
TI  - [Nature and magnitude of the need for dental care in Belgium: the point of view
      of dentists].
AB  - In most countries, oral and dental problems (decay, gingivitis, parodontitis,..)
      are frequent and impact on overall health. Such problems can often be avoided and
      treated. Health professionals and patients become gradually more aware of the
      importance of oral health. Oral hygiene and other measures may prevent several
      problems, which is beneficial to individuals and to public health, since the
      consequences of oral diseases are very expensive for all. Our study aims to
      analyze the features of the profession and to assess their possible evolution in
      the future. The design of our study combines two approaches: a quantitative study
      -based on data of the national health insurance scheme regarding utilization of
      care- and a qualitative study based on deep-interviews of dentists. According to
      the latter, dental care is expensive for the patient and also for professionals.
      The workload becomes heavier because patients expect too much. It is expanding,
      due to longer life expectancy and to medical progress which enables to conserve
      natural dentition, thus requiring extra care for the surviving teeth. These
      factors explain the increase of dental services which we highlight for the last
      20 years; for the future, most of services are expected to expand, mainly for
      elderly (65 + years), One exception is noticeable: a probable decrease of
      "traditional care" for young and adult populations (<65 years). The authorities
      should take these trends into account in order to cover such new requirements,
      while also introducing measures in order to limit potential undue demand.
      However, a few socioeconomic groups remain out of the care system: all disabled
      persons living in institutions (inter alia elderly in nursing homes);
      furthermore, the population of low socioeconomic status is unaware of the
      benefits of a good oral hygiene; professionals denounce these gaps of the system
      and suggest improvements. Education about oral hygiene should also be promoted;
      consequently, the profession of oral hygienist should obtain an official license.

PMID- 17439086
TI  - [Informal health care in Belgium].
AB  - Research on the provision of care is mostly based on household sample surveys,
      which cannot measure the prevalence of caregiving in the general population. In
      order to appraise the individuals' involvement in the provision of informal care,
      specific questions on the care provided were included in Belgium's 2001 Census.
      Using data from the census we aim at analyzing how the provision and the amount
      of informal care, varies with respect to the individual's socio-economic
      characteristics. We found that 1 out 10 Belgians provide informal care. As
      expected, most caregivers can be found among middle-aged women. Yet, the
      percentage of men and women providing informal care at home is quite similar. The
      education level has an unexpected influence on the provision of care: more
      educated individuals are more likely to be caregivers while lesser educated
      individuals are more likely to provide more hours of care. Given that informal
      care is a valuable resource for meeting the care needs of today's societies, more
      attention should be given to the consequences of providing it. Indeed, not
      considering the negative aspects of providing informal care, such as the
      deterioration in the health status of caregivers or the competing demands between
      working and caring, can lead to a reduction of the amount of informal care
      provided.

PMID- 17439087
TI  - The joint operation: "The Single Wealth is Man".

PMID- 17439088
TI  - ISUIA, ISAT and the National Study of Subarachnoid Haemorrhage: changing trends
      and implications for neurovascular services in the United Kingdom and Ireland.

PMID- 17439089
TI  - Pituitary apoplexy: retrospective review of 30 patients--is surgical intervention
      always necessary?
AB  - The objective of this article is to review clinical outcomes in patients
      presenting with pituitary apoplexy and compare the results of conservative and
      surgical management. It took the form of a retrospective review of 30 patients
      (23M, 7F; age range: 17-86 years) with pituitary apoplexy diagnosed between 1988
      and 2004. Presenting features included headache in 27 patients, 'collapse' in
      three and vomiting in 14. Complete blindness occurred in four patients, monocular
      blindness in two, decreased visual acuity in 12, visual field loss in 10 and
      ophthalmoplegia in 15. Only five had no initial visual deficit. CT was the
      initial mode of imaging in 22 patients: three such scans were initially reported
      as 'normal' and a further 10 as pituitary tumour only, with no haemorrhage. Ten
      patients proceeded to early pituitary surgery and 20 were managed conservatively.
      There was one death 24 days after admission in a patient with multiple co
      morbidities. Of the six patients with blindness, three (two conservatively
      treated) regained partial vision. Of the remaining 19 patients with visual
      deficits, 10 (two surgically treated) recovered fully and eight (four surgically
      treated) partly so. At latest follow-up the following pituitary hormone
      deficiencies were identified: ACTH 19; TSH 20; testosterone 18; ADH (diabetes
      insipidus) eight. Later recurrence of a pituitary adenoma was observed in seven
      cases (including six of the 10 surgically treated patients). There was no
      evidence that those patients managed surgically had a better outcome. Early
      neurosurgical intervention may not be required in most patients presenting with
      pituitary apoplexy.

PMID- 17439090
TI  - Transcranial doppler ultrasonography as an early outcome forecaster following
      severe brain injury.
AB  - Knowledge of post-traumatic cerebral haemodynamic disturbances might be
      beneficial for predicting the management outcome when measuring the basal
      cerebral arteries blood flow velocity by ultrasonic transcranial Doppler device
      immediately after severe head injury. Thirty patients who sustained severe brain
      injury underwent an early blood velocity measuring by transcranial Doppler
      ultrasonography during a 1-year period of study. The standard technique of
      measuring the mean blood flow velocity in the middle cerebral artery was applied.
      The outcome was assessed at 6-month follow-up by the Glasgow Outcome Score. The
      middle cerebral artery low blood flow velocity, and the increased values of the
      pulsatility index significantly correlated to an unfavourable outcome.
      Transcranial Doppler ultrasonography for measuring the middle cerebral artery
      blood flow velocity has been proved worthy as a possible predictor of severe head
      injury management outcome. This non-invasive and simple procedure could be
      engaged in the daily management of severely brain-injured patients.

PMID- 17439091
TI  - Laminectomy for lumbar canal stenosis: a safe and effective treatment.
AB  - Lumbar canal stenosis (LCS) is a common condition affecting elderly patients for
      which a significant number undergo surgery. The validity and safety of simple
      laminectomy in this condition is not fully understood. Furthermore, the presence
      of pre-existing spondylolisthesis is controversial with respect to the need for
      additional spinal stabilization. We prospectively studied a consecutive cohort of
      100 patients with clinical and radiological LCS under the care of a single spinal
      surgeon. Outcome measures (SF-36, visual analogue scores for back and leg
      symptoms, and the Roland/Morris back pain scores) were assessed preoperatively, 3
      months postsurgery and at long-term (median 2 years) follow-up. We have shown a
      significant improvement in outcome sustained in the long-term with minimal
      morbidity. Patients with pre-existing spondylolisthesis accounted for 23% of the
      cohort and, having received identical treatment, showed no significant difference
      in outcome compared with patients with normal alignment.

PMID- 17439092
TI  - Intraoperative mapping of sacral nervous system (S2-4).
AB  - Electrophysiological mapping of the sacral nervous system was used during
      operations on 80 patients with conus and cauda equina lesions. At surgery, under
      controlled muscle relaxation, the sacral neural elements (S2-4) were mapped using
      direct mono-polar stimulation and recording of compound muscle action potentials
      (CMAPs) from the external anal sphincter (EAS). Responses were obtained in 86.25%
      (69/80) of the patients. In 33 (82.5%) out of 40 patients with preoperative
      deficits involving the S2-4 segments, CMAPs could be elicited. Identification of
      nerve roots was useful in dissection of lipomyelomeningocoeles, tumour excisions
      and untethering of filum terminale. In three patients, stimulation of the filum
      terminale elicited motor responses and, hence, it was not sectioned.
      Intraoperative mapping of the S2-4 nerve roots under controlled muscle relaxation
      is feasible in a majority of patients, including those with deficits involving S2
      4. This method was useful in sparing viable nerve roots during surgery in conus
      and cauda equina regions, and identification of 'functional' filum terminale.

PMID- 17439093
TI  - Changes in plasma phenytoin level following craniotomy.
AB  - Phenytoin is often used to prevent postcraniotomy seizures, but is not always
      effective. We investigate changes in plasma phenytoin level ([phenytoin])
      following craniotomy. The [phenytoin] in 28 patients who were receiving phenytoin
      (oral/ intravenous) and undergoing a craniotomy were prospectively measured 24 h
      preoperatively, immediately pre- and postcraniotomy, 24 and 48 h postoperatively.
      Factors examined included patients' age, sex, pathology, preoperative
      [phenytoin], operative duration and blood loss. Fifteen patients had [phenytoin]
      concentrations outside the therapeutic range. Twenty-five patients experienced a
      decrease in [phenytoin] immediately postcraniotomy: pre-, post- and 24 h
      postcraniotomy mean [phenytoin] were 13.4, 10.0 and 12.9 mg/l, respectively.
      Preoperative [phenytoin], operative duration and blood loss had significant
      correlation with the decrease in [phenytoin] (p < 0.05). In conclusion, < 50% of
      the patients had therapeutic preoperative [phenytoin]. In most patients,
      [phenytoin] decreases by 26% after craniotomy and returns to preoperative level
      within 24 h. These may contribute to early postoperative seizure development.

PMID- 17439094
TI  - Lumbar cerebrospinal fluid pressure waves versus intracranial pressure waves in
      idiopathic normal pressure hydrocephalus.
AB  - The aim of this study was to explore how the lumbar cerebrospinal fluid pressure
      (CSFP) waves recorded during lumbar infusion compared with the intracranial
      pressure (ICP) waves recorded, either during lumbar infusion or during long-term,
      overnight monitoring. For this purpose, we assessed 27 simultaneous lumbar
      CSFP/ICP recordings made during lumbar infusion and 27 long-term, overnight ICP
      recordings in 27 consecutive idiopathic normal pressure hydrocephalus (iNPH)
      patients. Pressure waves during lumbar infusion were explored by computing pulse
      pressure amplitude and mean single wave pressure of every corresponding CSFP/ICP
      wave pair; among our 27 lumbar CSFP/ICP recordings a total of 35,532 CSFP/ICP
      wave pairs were available for analysis. We as well computed mean values of pulse
      pressure amplitude (i.e. mean CSFP wave amplitude or mean ICP wave amplitude) and
      mean values of mean single wave pressure (i.e. mean CSFP or mean ICP) during
      consecutive 6-s time windows, as well as average values for the individual
      recordings. During lumbar infusion, the cerebrospinal fluid pulse pressure
      amplitudes were about 2 mmHg smaller than the corresponding intracranial pulse
      pressure amplitudes. The mean CSFP wave amplitudes recorded during lumbar
      infusion correlated significantly with the mean ICP wave amplitudes recorded
      either during lumbar infusion or during long-term, overnight ICP monitoring. In
      21 of 27 lumbar infusion tests (78%), the presence of elevated lumbar mean CSFP
      waves was related to presence of elevated mean ICP wave amplitudes during long
      term, overnight ICP monitoring. Hence, the lumbar cerebrospinal fluid pulse
      pressure amplitudes recorded during lumbar infusion could be used to predict the
      intracranial pulse pressure amplitudes recorded during long-term, overnight ICP
      monitoring.

PMID- 17439095
TI  - Garre's chronic diffuse sclerosing osteomyelitis of the sacrum: a rare condition
      mimicking malignancy.
AB  - Garre's chronic diffuse sclerosing osteomyelitis (DSOM) is a rare disease that
      occurs most commonly in the mandible. We present a case of sacral DSOM that
      simulated an expanding destructive sacral tumour. Treatment was conducted on the
      basis of the available experience with the mandibular form of the disease, with
      partial symptomatic relief, but progressive sclerosis of the sacral lesion. To
      the best of our knowledge, this is the first case initially presenting in the
      sacrum. As an osteolytic expanding lesion simulating malignancy, it is important
      to recognize this entity in the sacrum.

PMID- 17439096
TI  - Orbital roof growing fractures: a report of four cases and literature review.
AB  - Trivial injuries among paediatric patients are usually underestimated. Such
      injuries may account for delayed problems such as growing fractures of skull
      vault. Growing fracture of the orbital roof is rarely reported. Four cases of
      paediatric cranial trauma with growing orbital roof fractures are presented.
      Three cases required only dural repair, while the fourth patient underwent both
      duraplasty and cranioplasty, due to a large orbital roof defect. At follow-up,
      all had satisfactory outcome. Trivial injuries among children should be evaluated
      with caution. The development of orbital symptomatology should ask for a complete
      radiological survey. The orbital roof growing fractures are potentially important
      cause of orbital problems. The dural repair alone, usually provides satisfactory
      outcome, while calvarial bone graft may be of help in cases with large bony
      defects. Early diagnosis and management of such cases may prevent permanent
      neurological deficits.

PMID- 17439097
TI  - Herpes zoster of the trigeminal nerve following microvascular decompression.
AB  - A patient developed herpes zoster of the maxillary division of the trigeminal
      nerve after microvascular decompression. Varicella zoster virus lies dormant in
      the Gasserian ganglion until reactivation and can cause herpes zoster
      ophthalmicus. This can result in serious ocular complications including
      blindness. Antiviral agents are effective if commenced promptly.

PMID- 17439098
TI  - Remodelling potential of paediatric cervical spine after type II odontoid peg
      fracture.
AB  - We describe a case of odontoid process fracture below the synchondrosis
      associated with delayed diagnosis and anterior subluxation of C1 over C2. This
      was treated with an in situ posterior occipitocervical fusion. Long-term follow
      up of 7 years showed excellent remodelling of the deformity.

PMID- 17439099
TI  - Multiple gangliogliomas of the optic pathway.
AB  - We report a case of multiple gangliogliomas of the optic pathway in an 18-year
      old boy. He presented with visual disturbance mainly in his left eye, non
      specific headaches, and episodes of sensory disturbance in his left arm. Visual
      acuity was 6/9 and 6/24 in his right and left eye respectively. He did not have
      any Lisch nodules. Optic atrophy was noted in his left eye. MRI scan revealed
      multiple enhancing lesions involving the optic chiasm, left optic tract, right
      lateral geniculate body, and right optic radiation in the temporal lobe.
      Stereotactic biopsy of the temporal tumour confirmed ganglioglioma. Multiple
      gangliogliomas of the optic pathway has not been hitherto described.

PMID- 17439100
TI  - CSF diversion in benign intracranial hypertension using a lumbo-atrial shunt.
AB  - An obese woman with benign intracranial hypertension had been managed for several
      years with lumbo-peritoneal shunting. Following a bilopancreatic procedure
      performed for management of her obesity dense peritoneal adhesions caused
      repeated shunt failure. The shunt system was successfully converted to a lumbo
      atrial system.

PMID- 17439101
TI  - Unusual recurrence of pleomorphic xanthoastrocytoma.

PMID- 17439102
TI  - Bilateral huge calcified chronic subdural haematomas ['armoured brain'] in an
      adult patient with a coexistent VA shunt infection.

PMID- 17439103
TI  - Modeling of branching ratio uncertainty in chemical networks by Dirichlet
      distributions.
AB  - Validation of complex chemical models relies increasingly on uncertainty
      propagation and sensitivity analysis with Monte Carlo sampling methods. The
      utility and accuracy of this approach depend on the proper definition of
      probability density functions for the uncertain parameters of the model. Taking
      into account the existing correlations between input parameters is essential to a
      reliable uncertainty budget for the model outputs. We address here the problem of
      branching ratios between product channels of a reaction, which are correlated by
      the unit value of their sum. We compare the uncertainties on predicted time
      dependent and equilibrium species concentrations due to input samples, either
      uncorrelated or explicitly correlated by a Dirichlet distribution. The method is
      applied to the case of Titan ionospheric chemistry, with the aim of estimating
      the effect of branching ratio correlations on the uncertainty balance of
      equilibrium densities in a complex model.

PMID- 17439104
TI  - Photophysics of alpha,omega-diphenyloctatetraene in the vapor phase.
AB  - Fluorescence and fluorescence excitation spectra of diphenyloctatetraene vapor
      have been measured at different temperatures from 98 to 136 degrees C and at
      different buffer gas pressures from 0 to 300 Torr. The fluorescence quantum
      yields were determined as functions of the excitation energy and buffer gas
      pressure. It is shown that diphenyloctatetraene vapor exhibits weak fluorescence
      from the S2 (1(1)Bu) state in addition to the fluorescence from the S1 (2(1)Ag)
      state. The quantum yield of the S1 fluorescence is shown to decrease with
      decreasing pressure and with increasing excitation energy. The electronic
      relaxation processes of diphenyloctatetraene vapor are discussed based on the
      pressure and excitation-energy dependence of the fluorescence quantum yield.

PMID- 17439105
TI  - Reduced multireference coupled-cluster method: barrier heights for heavy atom
      transfer, nucleophilic substitution, association, and unimolecular reactions.
AB  - The recently developed reduced multireference coupled-cluster method with singles
      and doubles (RMR CCSD) that is perturtatively corrected for triples [RMR CCSD(T)]
      is employed to compute the forward and reverse barrier heights for 19 non
      hydrogen-transfer reactions. The method represents an extension of the
      conventional single-reference (SR) CCSD(T) method to multireference situations.
      The results are compared with a benchmark database, which is essentially based on
      the SR CCSD(T) results. With the exception of seven cases, the RMR CCSD(T)
      results are almost identical with those based on SR CCSD(T), implying the
      abatement of MR effects at the SD(T) level relative to the SD level. Using the
      differences between the RMR CCSD(T) and CCSD(T) barrier heights as a measure of
      MR effects, modified values for barrier heights of studied reactions are given.

PMID- 17439106
TI  - The substituted alkyne 3-heptyne is eclipsed.
AB  - Although butane exists in staggered anti and gauche conformations, when the ethyl
      groups are separated by a C[triple bond]C triple bond (3-hexyne), the stable
      conformation changes to eclipsed, (1)C(2v). Using rotational microwave
      spectroscopy, we have studied another example, 3-heptyne, the C[triple bond]C
      elongated analogue of pentane. The most stable conformer of pentane has anti-anti
      (AA) conformations about the central C-C bonds (C(2v)) and the next most stable
      has a gauche dihedral angle (GA, C1). This microwave study determines that the
      extended analogue of the AA form is not staggered about the C[triple bond]C axis
      but eclipsed (Cs). Also, the elongated analogue of the GA conformer is also not
      staggered but nearly eclipsed. The conformations of low-polarity substituted
      acetylenes is determined by dispersion attractions between the end groups. A
      microwave study of the AA and GA conformers of pentane is also reported.

PMID- 17439107
TI  - Hydration and water-exchange mechanism of the UO2 2+ ion revisited: the validity
      of the "n + 1" model.
AB  - Hydration and water-exchange mechanism of the UO2(2+) ion was studied by the
      B3LYP calculations. Relative Gibbs energies in aqueous phase of the 4-, 5-, and 6
      fold uranyl(VI) hydrates were compared. A model with a complete first hydration
      shell and one water in the second shell was used (which is called "n + 1" model)
      to compare the energy of the UO2(2+) ion with different hydration numbers. The n
      + 1 model tends to overestimate the overall stability of the complex, and this
      type of model should be carefully used for the determination of the coordination
      number or the coordination mode such as unidentate or bidentate. A stable 5-fold
      uranyl(VI) hydrate goes through a very rapid water-exchange process via an
      associative (A-) mechanism keeping the 5-fold uranyl(VI) the dominant species.

PMID- 17439108
TI  - Luminescent chemical waves in the Cu(II)-catalyzed oscillatory oxidation of SCN-
      ions with hydrogen peroxide.
AB  - The oscillatory oxidation of thiocyanate ions with hydrogen peroxide, catalyzed
      by Cu2+ ions in alkaline media, was so far observed as occurring simultaneously
      in the entire space of the batch or flow reactor. We performed this reaction for
      the first time in the thin-layer reactor and observed the spatiotemporal course
      of the above process, in the presence of luminol as the chemiluminescent
      indicator. A series of luminescent patterns periodically starting from the random
      reaction center and spreading throughout the entire solution layer was reported.
      For a batch-stirred system, the bursts of luminescence were found to correlate
      with the steep decreases of the oscillating Pt electrode potential. These novel
      results open possibilities for further experimental and theoretical
      investigations of those spatiotemporal patterns, including studies of the
      mechanism of this chemically complex process.

PMID- 17439109
TI  - Matrix isolation infrared spectroscopic and theoretical study of group IV metal
      oxide clusters: M2O2 and M2O4.
AB  - Dinuclear titanium, zirconium, and hafnium oxide clusters, M2O2 and M2O4 (M = Ti,
      Zr, Hf) have been prepared and characterized by matrix isolation infrared
      spectroscopy and quantum chemical calculations. The M2O2 clusters were formed
      through the reactions of metal dimers and O2 in solid argon upon sample
      annealing. Theoretical calculations indicate that the Ti2O2 cluster has a singlet
      ground state with a nonplanar cyclic C(2v) structure with a strong Ti-Ti bond,
      while the Zr2O2 and Hf2O2 clusters have planar cyclic structures. The M2O4
      clusters were characterized to have a closed-shell singlet ground state with a
      nonplanar C2h symmetry, which were formed from the dimerization of the metal
      dioxide molecules.

PMID- 17439110
TI  - Theoretical study on the second hyperpolarizabilities of phenalenyl radical
      systems involving acetylene and vinylene linkers: diradical character and spin
      multiplicity dependences.
AB  - We have investigated the static second hyperpolarizabilities (gamma) of the
      singlet diradical systems with intermediate diradical character involving
      phenalenyl radicals connected by acetylene and vinylene pi-conjugated linkers, 1
      and 2, using the hybrid density functional theory. For comparison, we have also
      examined the gamma values of the closed-shell and pure diradical systems with
      almost the same molecular size as 1 and 2. In agreement with our previous
      prediction of the diradical character dependence of gamma, it turns out that the
      gamma values of 1 and 2 are significantly enhanced compared to those of the
      closed-shell and pure diradical systems. In the present case, distinct
      differences in gamma values are not observed between the two pi-conjugated
      linkers, though the diradical character is found to depend on the kind of linker.
      Furthermore, we have investigated the spin multiplicity effect on gamma. Changing
      from the singlet to the triplet state, the gamma values of the systems with
      intermediate diradical character in the singlet state are quite reduced, though
      those of the pure diradical systems are hardly changed. Such spin multiplicity
      dependence of gamma is understood by considering the difference of diradical
      character between their singlet states together with the Pauli principle. The
      present results provide a possibility of a novel control scheme of gamma for
      phenalenyl radical systems involving pi-conjugated linkers by adjusting the
      diradical character through the change of the linked position of pi-conjugated
      linkers and the spin multiplicity.

PMID- 17439111
TI  - The structure of uracil: a laser ablation rotational study.
AB  - The jet-cooled rotational spectrum of uracil has been investigated using laser
      ablation molecular beam Fourier transform microwave (LA-MB-FTMW) spectroscopy.
      The quadrupole structure originated by the two 14N nuclei of uracil has been
      completely resolved and assigned. This provides a definitive method to establish
      the pyrrolic or pyrimidinic nature of the N nuclei and allows us to conclude that
      the observed tautomer of uracil in the gas phase is the diketo form. From the
      rotational constants of the isotopic species detected, a structure of uracil has
      been determined.

PMID- 17439112
TI  - Novel series of potent, nonsteroidal, selective androgen receptor modulators
      based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones.
AB  - Recent interest in orally available androgens has fueled the search for new
      androgens for use in hormone replacement therapy and as anabolic agents. In
      pursuit of this, we have discovered a series of novel androgen receptor
      modulators derived from 7H-[1,4]oxazino[3,2-g]quinolin-7-ones. These compounds
      were synthesized and evaluated in competitive binding assays and an androgen
      receptor transcriptional activation assay. A number of compounds from the series
      demonstrated single-digit nanomolar agonist activity in vitro. In addition, lead
      compound (R)-16e was orally active in established rodent models that measure
      androgenic and anabolic properties of these agents. In this assay, (R)-16e
      demonstrated full efficacy in muscle and only partially stimulated the prostate
      at 100 mg/kg. These data suggest that these compounds may be utilized as
      selective androgen receptor modulators or SARMs. This series represents a novel
      class of compounds for use in androgen replacement therapy.

PMID- 17439113
TI  - Malaria-infected mice are cured by a single dose of novel artemisinin
      derivatives.
AB  - We disclose here for the first time the curative activity of a new generation of
      trioxane dimers, designed logically and prepared easily from the natural trioxane
      artemisinin in only four or five chemical steps that would be easily accomplished
      also on a manufacturing scale. Four of these trioxane dimers cure malaria
      infected mice after only a single subcutaneous dose, and two other dimers cure
      after three oral doses.

PMID- 17439114
TI  - Binding of nitrate to a CuII-cyclen complex bearing a ferrocenyl pendant:
      synthesis, solid-state X-ray structure, and solution-phase electrochemical and
      spectrophotometric studies.
AB  - The reaction of Cu(NO3)2.3H2O with the ligand 1-(ferrocenemethyl)-1,4,7,10
      tetraazacyclododecane (L) in acetonitrile leads to the formation of a blue
      complex, [Cu(L)(NO3)][NO3] (C1). The X-ray structure determination shows an
      unexpected binding of a nitrate anion in that the CuII center is surrounded by
      four N atoms of the 1,4,7,10-tetraazacyclododecane (cyclen) macrocycle and two O
      atoms from a chelating nitrate anion, both Cu-O distances being below the sums of
      the van de Waals radii. Hydrogen-bonding interactions in the crystal lattice and
      a weak interaction between a second nitrate O and the CuII center in C1 give rise
      to a highly distorted CuII geometry relative to that found in the known structure
      of [Cu(cyclen)(NO3)][NO3] (C5). Electrochemical studies in acetonitrile
      containing 0.1 M [Bu4N][NO3] as the supporting electrolyte showed that oxidation
      of C1 in this medium exhibits a single reversible one-electron step with a formal
      potential E degrees f of +85 mV vs Fc0/+ (Fc = ferrocene). This process is
      associated with oxidation of the ferrocenyl pendant group. Additionally, a
      reversible one-electron reduction reaction with an E degrees f value of -932 mV
      vs Fc0/+, attributed to the CuII/I redox couple, is detected. Gradual change of
      the supporting electrolyte from 0.1 M [Bu4N][NO3] to the poorly coordinating
      [Bu4N][PF6] electrolyte, at constant ionic strength, led to a positive potential
      shift in E degrees f values by +107 and +39 mV for the CuII/I(C1) and Fc0/+(C1)
      redox couples, respectively. Analysis of these electrochemical data and UV-vis
      spectra is consistent with the probable presence of the complexes C1,
      [Cu(L)(CH3CN)2]2+ (C2), [Cu(L)(CH3CN)(NO3)]+ (C3), and [Cu(L)(NO3)2] (C4) as the
      major species in nitrate-containing acetonitrile solutions. In weakly solvating
      nitromethane, the extent of nitrate complexation remains significant even at low
      nitrate concentrations, due to the lack of solvent competition.

PMID- 17439115
TI  - Varying acidity of aqua ligands in dependence on the microenvironment in
      mononucleobase (nb) complexes of type cis- and trans-[Pt(NH3)2(nb)(H2O)]n+.
AB  - Aqua ligands in mixed aqua/nucleobase metal complexes are potential sites of acid
      base catalysis and/or, when present as hydroxo ligands, can directly be involved
      in hydrolysis reactions. pKa values of close to 7 are consequently of particular
      interest and potential significance. Here we report on the differential acidity
      of aqua complexes in model nucleobase (nb) complexes of cis- and trans-[Pt(NH3)2
      (nb)(H2O)]n+ and discuss reasons as to why the nb in cis complexes influences the
      pKa (pKa 4.8-7.0), whereas in trans complexes the pKa values are rather constant
      (pKa approximately 5.2-5.3). The results of DFT calculations of a series of
      mono(nucleobase) complexes derived from cis-Pt(NH3)2 are critically examined with
      regard to the role of exocyclic groups of nucleobases in stabilizing aqua/hydroxo
      ligands through intracomplex hydrogen bond formation. This applies in particular
      to the exocyclic amino groups of nucleobases, for which gas-phase calculations
      suggest that they may act as H bond acceptors in certain cases, yet in the
      condensed phase this appears not to be the case.

PMID- 17439116
TI  - Transformation of AeIn4 Indides (Ae=Ba, Sr) into an AeAu2In2 structure type
      through gold substitution.
AB  - The title compounds were prepared from the elements by high-temperature solid
      state synthesis techniques. X-ray structural analyses shows that BaAu2In2 (1) and
      SrAu2In2 (2) crystallize in a new orthorhombic structure, Pnma, Z=4 (a=8.755(2),
      8.530(2) A; b=4.712(1), 4.598(1) A; c=12.368(3), 12.283(4) A, respectively). Gold
      substitutes for 50% of the indium atoms in the tetragonal BaIn4 and monoclinic
      SrIn4 parents to give this new and more flexible orthorhombic structure. The Ae
      atoms in this structure are contained within chains of hexagonal prisms built of
      alternating In and Au that have additional augmenting atoms around their waists
      from further condensation of parallel displaced chains. The driving forces for
      these structural changes are in part the shorter Au-In distances (2.72 and 2.69
      A) relative to d(In-In) in the parents, presumably because of relativistic
      contractions with Au. Generalities about such centered prismatic building blocks
      and their condensation modes in these and related phases are described. Band
      structure calculations (EHTB) demonstrate that the two compounds are metallic,
      which is confirmed by measurements of the resistivity of 1 and the magnetic
      susceptibilities of both.

PMID- 17439118
TI  - Transition state analysis of model and enzymatic prenylation reactions.

PMID- 17439117
TI  - Molecular analysis of the benastatin biosynthetic pathway and genetic engineering
      of altered fatty acid-polyketide hybrids.
AB  - The entire gene locus encoding the biosynthesis of the potent glutathione-S
      transferase inhibitors and apoptosis inducers benastatin A and B has been cloned
      and sequenced. The cluster identity was unequivocally proven by deletion of
      flanking regions and heterologous expression in S. albus and S. lividans.
      Inactivation and complementation experiments revealed that a KSIII component
      (BenQ) similar to FabH is crucial for providing and selecting the rare hexanoate
      PKS starter unit. In the absence of BenQ, several novel penta- and hexacyclic
      benastatin derivatives with antiproliferative activities are formed. In total,
      five new compounds were isolated and fully characterized, and the chemical
      analysis was confirmed by derivatization. The most intriguing observation is that
      the ben PKS can utilize typical straight and branched fatty acid synthase
      primers. If shorter straight-chain starters are utilized, the length of the
      polyketide backbone is increased, resulting in the formation of an extended,
      hexacyclic ring system reminiscent of proposed intermediates in the griseorhodin
      and fredericamycin pathways. Analysis and manipulation of the hybrid fatty acid
      polyketide pathway provides strong support for the hypothesis that the number of
      chain elongations is dependent on the total size of the polyketide chain that is
      accommodated in the PKS enzyme cavity. Our results also further substantiate the
      potential of metabolic engineering toward polyphenols with altered substituents
      and ring systems.

PMID- 17439119
TI  - Protein tyrosine phosphatase oligomerization studied by a combination of 15N NMR
      relaxation and 129Xe NMR. Effect of buffer containing arginine and glutamic acid.
AB  - 15N NMR relaxation and 129Xe NMR chemical shift measurements offer complementary
      information to study weak protein-protein interactions. They have been applied to
      study the oligomerization equilibrium of a low-molecular-weight protein tyrosine
      phosphatase in the presence of 50 mM arginine and 50 mM glutamic acid. These
      experimental conditions are shown to enhance specific protein-protein
      interactions while decreasing nonspecific aggregation. In addition, 129Xe NMR
      chemical shifts become selective reporters of one particular oligomer in the
      presence of arginine and glutamic acid, indicating that a specific Xe binding
      site is created in the oligomerization process. It is suggested that the multiple
      effects of arginine and glutamic acid are related to their effective excluded
      volume that favors specific protein association and the destabilization of
      partially unfolded forms that preferentially interact with xenon and are
      responsible for nonspecific protein aggregation.

PMID- 17439120
TI  - S(N)Ar displacements with 6-(fluoro, chloro, bromo, iodo, and
      alkylsulfonyl)purine nucleosides: synthesis, kinetics, and mechanism1.
AB  - SNAr reactions with 6-(fluoro, chloro, bromo, iodo, and alkylsulfonyl)purine
      nucleosides and nitrogen, oxygen, and sulfur nucleophiles were studied. Pseudo
      first-order kinetics were measured with 6-halopurine compounds, and comparative
      reactivities were determined versus a 6-(alkylsulfonyl)purine nucleoside. The
      displacement reactivity order was: F > Br > Cl > I (with BuNH2/MeCN), F > Cl
      approximately Br > I (with MeOH/1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)/MeCN),
      and F > Br > I > Cl [with K+ -SCOCH3/dimethyl sulfoxide (DMSO)]. The order of
      reactivity with a weakly basic arylamine (aniline) was: I > Br > Cl > F (with 5
      equiv of aniline in MeCN at 70 degrees C). However, those reactions with aniline
      were autocatalytic and had significant induction periods ( approximately 50 min
      for the iodo compound and approximately 6 h for the fluoro analogue). Addition of
      trifluoroacetic acid (TFA) eliminated the induction period, and the order then
      was F > I > Br > Cl (with 5 equiv of aniline and 2 equiv of TFA in MeCN at 50
      degrees C). The 6-(alkylsulfonyl)purine nucleoside analogue was more reactive
      than the 6-fluoropurine compound with both MeOH/DBU/MeCN and iPentSH/DBU/MeCN and
      was more reactive than the Cl, Br, and I compounds with BuNH2 and aniline/TFA.
      Titration of the 6-halopurine nucleosides in CDCl3 with TFA showed progressive
      downfield 1H NMR chemical shifts for H8 (larger) and H2 (smaller). The major site
      of protonation as N7 for both the 6-fluoro and 6-bromo analogues was confirmed by
      large upfield shifts ( approximately 16 ppm) of the 15N NMR signal for N7 upon
      addition of TFA (1.6 equiv). Mechanistic considerations and resolution of prior
      conflicting results are presented.

PMID- 17439121
TI  - Closo-alanes (Al4H4, AlnHn+2, 4 <or= n <or= 8): a new chapter in aluminum hydride
      chemistry.
AB  - Anion photoelectron spectroscopy and density functional theory were employed to
      study aluminum hydride clusters, AlnHm- (4 <or= n <or= 8, 0 <or= m <or= 10).
      Photoelectron spectra revealed that Al4H4, Al4H6, and a family of species with
      general formula AlnHn+2 (5 <or= n <or= 8) have small adiabatic electron
      affinities and large HOMO-LUMO gaps (ranging from 0.5 to 1.9 eV) relative to
      those of their stoichiometric neighbors, implying their enhanced stabilities.
      Formulas reminiscent of boranes led us to investigate whether Wade's rules could
      be applied to alanes as well. DFT calculations showed that the AlnHn+2 (5 <or= n
      <or= 8) family adopts n-vertex polyhedral closo-structures with two extra
      hydrogen atoms occupying opposite bridging positions in agreement with the Wade's
      (n + 1) rule. These can be viewed as aluminum versions of hypothetical
      diprotonated closo-borane dianions (BnHn2- + 2H+). In addition, Al4H4 assumes a
      closo-tetrahedral geometry, while Al4H6 takes on a distorted tetrahedral (D2d)
      structure with two counter-positioned bridging hydrogen atoms and has the largest
      HOMO-LUMO gap (1.9 eV) of all the alanes we studied. All of these species can be
      understood in terms of underlying polyhedral skeletal electron pair theory
      (PSEPT) concepts. Although, the herein studied alanes do not have direct borane
      analogues, the ability to understand their structures in terms of the Wade-Mingos
      rules and the underlying PSEPT concepts suggests that they can be considered as
      borane analogues, thereby opening a new chapter in aluminum hydride chemistry.

PMID- 17439122
TI  - Practical synthesis of enantiomerically pure beta2-amino acids via proline
      catalyzed diastereoselective aminomethylation of aldehydes.
AB  - Proline-catalyzed diastereoselective aminomethylation of aldehydes using a chiral
      iminium ion, generated from a readily prepared precursor, provides alpha
      substituted-beta-amino aldehydes with 85:15 to 90:10 dr. The alpha-substituted
      beta-amino aldehydes can be reduced to beta-substituted-gamma-amino alcohols, the
      major diastereomer of which can be isolated via crystallization or column
      chromatography. The amino alcohols are efficiently transformed to protected beta2
      amino acids, which are valuable building blocks for beta-peptides, natural
      products, and other interesting molecules. Because conditions for the
      aminomethylation and subsequent reactions are mild, beta2-amino acid derivatives
      with protected functional groups in the side chain, such as beta2-homoglutamic
      acid, beta2-homotyrosine, and beta2-homolysine, can be prepared in this way. The
      synthetic route is short, and purifications are simple; therefore, this method
      enables the preparation of protected beta2-amino acids in useful quantities.

PMID- 17439123
TI  - Sir2 deacetylases exhibit nucleophilic participation of acetyl-lysine in NAD+
      cleavage.

PMID- 17439124
TI  - Small-molecule inhibitors of protein geranylgeranyltransferase type I.

PMID- 17439125
TI  - Tuning the release rate of acidic degradation products through macromolecular
      design of caprolactone-based copolymers.
AB  - Macromolecular engineering is presented as a tool to control the degradation rate
      and release rate of acidic degradation products from biomedical polyester ethers.
      Three different caprolactone/1,5-dioxepan-2-one (CL/DXO) copolymers were
      synthesized: DXO/CL/DXO triblock, CL/DXO multiblock, and random cross-linked
      CL/DXO copolymer. The relation of CL and DXO units in all three copolymers was
      60/40 mol %. The polymer discs were immersed in phosphate buffer solution at pH
      7.4 and 37 degrees C for up to 364 days. After different time periods degradation
      products were extracted from the buffer solution and analyzed. In addition mass
      loss, water absorption, molecular weight changes, and changes in thermal
      properties were determined. The results show that the release rate of acidic
      degradation products, a possible cause of acidic microclimates and inflammatory
      responses, is controllable through macromolecular design, i.e., different
      distribution of the weak linkages in the copolymers.

PMID- 17439126
TI  - Structure-based engineering of a plant type III polyketide synthase: formation of
      an unnatural nonaketide naphthopyrone.
AB  - Pentaketide chromone synthase (PCS) from Aloe arborescens is a novel plant
      specific type III polyketide synthase (PKS) that produces 5,7-dihydroxy-2
      methylchromone from five molecules of malonyl-CoA. On the basis of the crystal
      structures of wild-type and M207G mutant PCS, the F80A/Y82A/M207G triple mutant
      was constructed and shown to produce an unnatural novel nonaketide naphthopyrone
      by sequential condensations of nine molecules of malonyl-CoA. This is the first
      demonstration of the formation of a nonaketide by the structurally simple type
      III PKS. A homology model predicted that the active-site cavity volume of the
      triple mutant is increased to 4 times that of the wild-type PCS.

PMID- 17439127
TI  - Counterions release from electrostatic complexes of polyelectrolytes and proteins
      of opposite charge: a direct measurement.

PMID- 17439128
TI  - Synthesis of hollow iron nanoframes.

PMID- 17439129
TI  - Synthesis and reactions of 20 pi-electron beta-tetrakis(trifluoromethyl)-meso
      tetraphenylporphyrins.

PMID- 17439130
TI  - Synthesis of organic photodimeric cage molecules based on cycloaddition via metal
      ligand directed assembly.

PMID- 17439131
TI  - An efficient and chemoselective iron catalyst for the hydrogenation of ketones.

PMID- 17439132
TI  - A unified synthetic approach to polyketides having both skeletal and
      stereochemical diversity.
AB  - An efficient systematic approach to the diversity-oriented synthesis of
      polyketides has been developed to provide both skeletal and stereochemical
      diversity. Each synthetic intermediate is also a desired polyketide fragment and
      no protecting group manipulations are required. A first-generation synthesis
      provides a 74-membered polyketide library comprising six different skeletal
      classes, each in one to five steps from propargylic alcohol precursors. A study
      of epoxyol opening reactions revealed unusual reactivity trends based on epoxide
      configuration.

PMID- 17439133
TI  - Copper-catalyzed cyclization of steroidal acylaminoacetylenes: syntheses of novel
      11beta-aryl-17,17- spiro[(4'H,5'-methylene)oxazol]-substituted steroids.
AB  - A variety of novel 11beta-aryl-17,17-spiro[(4'H,5'-methylene)oxazol]-substituted
      steroids have been synthesized in moderate to good yields via copper-catalyzed
      cyclization of acylaminoacetylenes. The best result was obtained with a catalytic
      amount of CuI in 1:1 benzene-Et3N at 90 degrees C for 30 min (Ar = 3,4
      difluorophenyl; R = ethyl; 97% yield).

PMID- 17439134
TI  - Thermal and photochemical racemization of chiral aromatic sulfoxides via the
      intermediacy of sulfoxide radical cations.
AB  - Efficient racemization of enantiomerically pure methyl aryl sulfoxides was
      obtained by N-methylquinolinium tetrafluoborate (NMQ+) sensitized photolysis and
      by one-electron oxidation catalyzed by tris(2,2'-bipyridyl)ruthenium(III)
      hexafluorophosphate.

PMID- 17439135
TI  - Synthesis of multisubstituted furans, pyrroles, and thiophenes via ynolates.
AB  - An efficient synthetic method for the preparation of multisubstituted furans,
      thiophenes, and pyrroles using ynolates was developed. This novel formal [4 + 1]
      annulation by C2-C3 and C3-C4 bond formations includes cycloaddition,
      cyclization, decarboxylation, and dehydration as key steps.

PMID- 17439136
TI  - Highly enantioselective alpha-aminoxylation of aldehydes and ketones with a
      polymer-supported organocatalyst.
AB  - The first catalytic enantioselective alpha-aminoxylation of aldehydes and ketones
      using an insoluble, polymer-supported organocatalyst (1) derived from trans-4
      hydroxyproline is reported (ee: 96-99%). Reaction rates in the aminoxylation of
      cyclic ketones with 1 are higher than those reported with l-proline. The
      insoluble nature of 1 simplifies workup conditions and allows catalyst recycling
      without an apparent decrease in enantioselectivity or yield.

PMID- 17439137
TI  - Ene-yne tetrahydrofurans from the sponge Xestospongia muta. exploiting a weak CD
      effect for assignment of configuration.
AB  - Seven new brominated ene-yne tetrahydrofurans (THFs), mutafurans A-G, were
      isolated from the Bahamian sponge Xestospongia muta. The absolute configuration
      of the natural products was assigned as (5R,8S) by interpretation of the Cotton
      effect arising from weak perturbation of an ene-yne chromophore by a propargylic
      THF ring.

PMID- 17439138
TI  - Carbocupration of 1-alkynylphosphines followed by trapping with electrophiles.
AB  - Treatment of 1-alkynylphosphine with magnesium dialkylcuprate in ether results in
      regio- and stereoselective syn-carbocupration. The alkenylcopper intermediate
      reacts with electrophile, which leads to allylation, acylation, and
      phosphination. The phosphination offers a new route to gem-diphosphinoalkene, an
      interesting phosphorus-based organic structure.

PMID- 17439139
TI  - Effects of enrichment of refined olive oil with phenolic compounds from olive
      leaves.
AB  - The possibility of preparing olive oil, with the same nutritional value and
      stability characteristics found in virgin olive oil, by the enrichment of refined
      olive oil with olive leaf polyphenols was studied. To obtain antioxidant phenols
      similar to those found in virgin olive oil, these components were extracted from
      the leaves of several olive cultivars from the Northern region of Portugal,
      namely, Carrasca, Ripa, Negruche, Cordovil, Verdeal, Madural, and Bical
      cultivars, under several conditions. The concentration of a leaf extract required
      for addition to refined olive oil to obtain the same stability as virgin olive
      oil was determined. The extract from 1 kg of leaves was sufficient to fortify 50
      320 L of refined olive oil to a similar stability as a virgin olive oil sample
      depending on the metal concentration of the oil, cultivar, and time of the year
      when the leaves were picked.

PMID- 17439140
TI  - Simultaneous determination of neonicotinoid insecticides in agricultural samples
      by solid-phase extraction cleanup and liquid chromatography equipped with diode
      array detection.
AB  - Effective sample pretreatment procedures based on solid-phase extraction (SPE)
      for multiresidue determination of seven neonicotinoid insecticides in
      agricultural products were investigated. After extraction with acetone and
      concentration, the insecticides in aqueous sample extracts were transferred into
      organic solvent phases with a Chem Elut SPE cartridge. Finally, the eluate from
      the cartridge was cleaned up with a SPE cartridge packed with graphitized carbon
      black and aminopropyl silica gel, which showed a higher cleanup efficiency than
      the classical silica gel SPE cartridge. Seven insecticides were separated on a
      reversed-phase C18 column and a gradient system of methanol and phosphate
      solution based on high-performance liquid chromatography. The established
      multiresidue determination has been applied to several artificially spiked
      agricultural samples, with the result that the average recoveries were excellent,
      with the exception of nitenpyram. The limit of detection of the method ranged
      from 0.01 to 0.03 mg/kg for the insecticides.

PMID- 17439141
TI  - Conformational and rheological changes in catfish myosin as affected by different
      acids during acid-induced unfolding and refolding.
AB  - Changes in the conformation of catfish (Ictalurus punctatus) myosin due to (i)
      anions, (ii) acid pH, and (iii) salt addition were determined using tryptophan
      fluorescence, hydrophobicity measurements, differential scanning calorimetry, and
      circular dichroism. The relationship between conformation and storage modulus
      (G') of acid-treated myosin was studied. Three acids, HCl, H2SO4, and H3PO4, were
      used for unfolding myosin at three acidic pH conditions, 1.5, 2.0, and 2.5.
      Unfolded myosin was refolded to pH 7.3. Denaturation and unfolding of myosin was
      significantly (p < 0.05) lower when salt (0.6 M NaCl) was present during acid
      unfolding than in the absence of salt. When salt was added before unfolding, the
      alpha-helix content of myosin treated at pH 1.5 was significantly lower than that
      treated at pH 2.5. When salt was added after refolding, the alpha-helix content
      of myosin was unaffected by different pH treatments. The G' of myosin increased
      with an increase in myosin denaturation. The G' of myosin was significantly (p <
      0.05) higher when salt was added to myosin after refolding than before acid
      unfolding. Among the different anion treatments, the G' of acid-treated myosin
      decreased in the order Cl- approximately SO42- > PO43-. Among the different pH
      treatments, the G' of myosin treated at pH 1.5 was significantly (p < 0.05)
      higher than myosin treated at pH 2.5. The conditions that would result in maximum
      myosin denaturation and maximum G' were unfolding of myosin at pH 1.5 using Cl-
      (from HCl) followed by refolding at pH 7.3 and subsequent addition of 0.6 M NaCl.

PMID- 17439142
TI  - Acid gelation in heated and unheated milks: interactions between serum protein
      complexes and the surfaces of casein micelles.
AB  - The acid-induced interactions between different protein particles in milk (casein
      micelles and serum protein/kappa-casein complexes) were studied in a series of
      different mixtures of heated and unheated proteins using diffusing wave
      spectroscopy (DWS) and small deformation rheology. The measurements were made as
      functions of pH during acidification by addition of glucono-delta-lactone (GDL).
      Heat treatment (85 degrees C, 10 min) affected the composition of the serum and
      the reactivity of casein micellar surface based on the pH at which the casein
      micelles aggregated during acidification. It was observed that the gel points as
      defined by DWS and rheology did not always coincide. The experiments showed that
      all systems containing heated serum proteins gelled at a higher pH than those
      containing unheated serum proteins. For systems containing heated micelles, an
      intermediate network can be formed between heat-induced aggregates of serum
      proteins and kappa-casein formed at the surfaces of the micelles and dispersed as
      soluble complexes in the serum. This can explain the observation that DWS
      measurements detected aggregation of casein micelles at an earlier stage than did
      rheology. For systems containing unheated micelles and soluble complexes from
      heated milk, the results appear to be explained only by a direct interaction
      between soluble serum protein complexes and the casein micelles themselves, once
      the pH has decreased to below about 5.5. Comparison of the different systems
      studied gives a more complete description of the possible mechanism of
      interaction of the different protein materials during the acid-induced
      coagulation of milk-based systems.

PMID- 17439143
TI  - Optimization of the trienzyme extraction for the microbiological assay of folate
      in vegetables.
AB  - Response surface methodology was applied to optimize the trienzyme digestion for
      the extraction of folate from vegetables. Trienzyme extraction is a combined
      enzymatic digestion by protease, alpha-amylase, and conjugase (gamma-glutamyl
      hydrolase) to liberate the carbohydrate and protein-bound folates from food
      matrices for total folate analysis. It is the extraction method used in AOAC
      Official Method 2004.05 for assay of total folate in cereal grain products.
      Certified reference material (CRM) 485 mixed vegetables was used to represent the
      matrix of vegetables. Regression and ridge analysis were performed by statistical
      analysis software. The predicted second-order polynomial model was adequate (R2 =
      0.947), without significant lack of fit (p > 0.1). Both protease and alpha
      amylase have significant effects on the extraction. Ridge analysis gave an
      optimum trienzyme digestion time: Pronase, 1.5 h; alpha-amylase, 1.5 h; and
      conjugase, 3 h. The experimental value for CRM 485 under this optimum digestion
      was close to the predicted value from the model, confirming the validity and
      adequacy of the model. The optimized trienzyme digestion condition was applied to
      five vegetables and yielded higher folate levels than the trienzyme digestion
      parameters employed in AOAC Official Method 2004.05.

PMID- 17439144
TI  - Comparison of the forage and grain composition from insect-protected and
      glyphosate-tolerant MON 88017 corn to conventional corn (Zea mays L.).
AB  - The next generation of biotechnology-derived products with the combined benefit
      of herbicide tolerance and insect protection (MON 88017) was developed to
      withstand feeding damage caused by the coleopteran pest corn rootworm and over
      the-top applications of glyphosate, the active ingredient in Roundup herbicides.
      As a part of a larger safety and characterization assessment, MON 88017 was grown
      under field conditions at geographically diverse locations within the United
      States and Argentina during the 2002 and 2003-2004 field seasons, respectively,
      along with a near-isogenic control and other conventional corn hybrids for
      compositional assessment. Field trials were conducted using a randomized complete
      block design with three replication blocks at each site. Corn forage samples were
      harvested at the late dough/early dent stage, ground, and analyzed for the
      concentration of proximate constituents, fibers, and minerals. Samples of mature
      grain were harvested, ground, and analyzed for the concentration of proximate
      constituents, fiber, minerals, amino acids, fatty acids, vitamins, antinutrients,
      and secondary metabolites. The results showed that the forage and grain from MON
      88017 are compositionally equivalent to forage and grain from control and
      conventional corn hybrids.

PMID- 17439145
TI  - Extraction and separation of water-soluble proteins from different wheat species
      by acidic capillary electrophoresis.
AB  - Optimization of protein extraction and a capillary zone electrophoresis method
      for water-soluble protein analysis in wheat is described. The optimal separation
      was obtained with a 50 microm i.d. x 27 cm (20 cm to detector) uncoated capillary
      filled with 0.1 M phosphoric acid/beta-alanine, pH 2.5, buffer containing urea (1
      M), 0.05% (w/v) hydroxypropylmethylcellulose, and 20% (v/v) acetonitrile.
      Separation was carried out at 15 kV and 35 degrees C for 9 min. Extract stability
      was also investigated within 2 h from the extraction. Good visual peak parameters
      and a higher sensitivity can be obtained when 30% ethanol is used as an
      extraction medium. The method was successfully used to analyze extracts obtained
      from whole and refined meals of six Triticum spp. Moreover, the described
      methodology could be applied to the discrimination of species with different
      ploidy levels and to the detection of durum wheat adulteration, as well as to
      screen wheat collections for enzymes involved with the quality of wheat
      derivatives.

PMID- 17439146
TI  - Effectiveness of microsatellite DNA markers in checking the identity of protected
      designation of origin extra virgin olive oil.
AB  - Collina di Brindisi is an Italian extra virgin olive oil that obtained the mark
      of protected designation of origin (PDO) according to EC Regulation 2081/92. The
      varietal requirements of the official production protocol of this oil foresee
      that this oil is prepared from cultivar Ogliarola (minimum 70%) and other Olea
      europaea L. cultivars that are diffused in the production area, accounting for a
      maximum of 30%. The aim of this work was to verify the effectiveness of
      microsatellite analysis in verifying the identity of Collina di Brindisi PDO
      olive oil. A preliminary assessment of product's quality by means of chemical
      analyses was also carried out. Microsatellite analysis clarified that the generic
      name Ogliarola, indicated in the technical sheet of this PDO oil, actually
      corresponded to the Ogliarola salentina cultivar. Furthermore, the obtained
      results showed that the examination of a limited number of DNA microsatellites
      enables the identification of the Ogliarola salentina cultivar in this PDO oil.

PMID- 17439147
TI  - Identification of an allele attributable to formation of cucumber-like flavor in
      wild tomato species (Solanum pennellii) that was inactivated during
      domestication.
AB  - Carbon 6 (C6)-aldehydes formed by fatty acid 13-hydroperoxide lyase (13HPL)
      specific to fatty acid 13-hydroperoxides (13-HPO) are important flavor
      constituents in fresh tomato fruits. C9-aldehydes are usually formed by 9/13HPL
      showing dual specificity to 9- and 13-HPOs and are scarcely found in tomato
      fruits. Mature red fruits of one of the introgression lines, IL1-4, generated by
      hybridization of a cultivated tomato (Solanum lycopersicon) to its wild relative
      Solanum pennellii, form high amounts of C9-aldehydes upon homogenization. The IL1
      4 fruits showed high 9/13HPL activity. One of the genes isolated from IL1-4
      showed a high similarity to plant 9/13HPLs. Recombinant proteins expressed in
      Escherichia coli showed 9/13HPL activity. Cleaved amplified polymorphic sequence
      analyses indicated that the gene was specific to IL1-4 and S. pennellii. S.
      lycopersicon had a gene having high similarity to the S. pennellii gene. It was
      absent in IL1-4. Among the differences of amino acid residues found between the
      two genes, a Cys to Ser exchange may be responsible for the inactivation of
      resultant protein product of S. lycopersicon gene because the Cys is an essential
      amino acid residue for HPL activity. From these observations, it could be assumed
      that a tomato gene corresponding to S. pennellii 9/13HPL gene had been
      inactivated through domestication of tomatoes.

PMID- 17439148
TI  - Studies on the effect of Amadoriase from Aspergillus fumigatus on peptide and
      protein glycation in vitro.
AB  - Amadoriase I is a fructosyl amine oxidase from Aspergillus fumigatus that
      catalyzes the oxidation of Amadori products (APs) producing glucosone, H2O2, and
      the corresponding free amine. All the enzymes of this family discovered so far
      only deglycate small molecular weight products and are inactive toward large
      molecular weight substrates, such as glycated BSA or ribonuclease A. Therefore,
      they cannot be used to reverse protein glycation occurring in diabetes or in
      foods. In this paper, the effect of Amadoriase I added during the in vitro
      reaction between glucose and peptides having different polarities or proteins
      with molecular weights ranging from to 5 to 66 kDa was tested. The formation of
      APs was monitored by ESI-MS of intact glycated protein or peptides and by
      measuring the Nepsilon-(1-deoxy-d-fructos-1-yl)-L-lysine and furosine
      concentrations. Results showed that the formation of APs is reduced up to 80%
      when peptides and glucose are incubated in the presence of Amadoriase. The effect
      is more evident for hydrophobic peptides. In protein-glucose systems, the effect
      was dependent on the molecular weight and steric hindrance being negligible for
      BSA and at a maximum for insulin, where the formation of APs was reduced up to
      60%. These findings indicate new potential applications of Amadoriase I as an
      efficient tool for inhibiting protein glycation in real food systems.

PMID- 17439149
TI  - Conformation of Napin (Brassica juncea) in salts and monohydric alcohols:
      contribution of electrostatic and hydrophobic interactions.
AB  - Napin from mustard (Brassica juncea L.) is a seed storage protein consisting of
      two subunits linked through disulfide bonds and is predominantly helical in
      nature. Resistance to trypsin digestion and allergenicity limit its food
      applications. The role of disulfide linkages, electrostatic as well as
      hydrophobic interactions, in napin stability have been investigated through
      spectroscopic methods, employing different fluorescent probes and additives. The
      subunits are hydrophilic in nature and possess extended structure. With the
      addition of 0.5 M NaCl, the surface hydrophobicity of napin decreases, whereas
      the helical content increases by 25%. In the presence of NaCl, emission maximum
      shifts toward shorter wavelength and the Stern-Volmer constant decreases from 6.5
      to 3.4 M-1, indicating compaction of napin. Na2SO4 has no significant effect on
      the structure due to the lack of a hydrophobic core. In the presence of
      monohydric alcohols and trifluoroethanol, there is an increase in ordered
      structure. These studies indicate that the structure of napin, which is
      hydrophilic in nature, is stabilized by electrostatic interactions, in addition
      to disulfide linkages.

PMID- 17439150
TI  - Evaluation of the performance of flow-through anodic fenton treatment in amide
      compound degradation.
AB  - A flow-through anodic Fenton treatment (FAFT) system based on the batch AFT
      technology was previously developed to degrade pesticides in aqueous solution. As
      one of a series of benchtop and pilot-scale studies in process optimization, the
      goal of the reported work is to evaluate the performance of the FAFT system under
      various operating conditions, which is critical to bringing this technology into
      practical general use in the field. For this purpose, the removal efficiency of
      the parent pesticide and the concentration of the hydroxyl radical in FAFT were
      calculated on the basis of a previously developed FAFT kinetic model and used for
      the evaluation. N,N-Diethyl-3-methylbenzamide (DEET), an insect repellent, was
      used as a chemical probe. Experimental data showed that the key to a high
      treatment efficiency is to operate the FAFT system to achieve a maximum *OH
      production with a minimum input of energy and chemicals. For the anodic half
      cell, the system should be operated under flow-through conditions with a self
      developed optimum pH of 3.0, a relatively high flow rate, and the initial
      effluent recycled within 6-10 min to the FAFT system for further treatment; for
      the cathodic half-cell, it should have a fixed volume and be entirely replaced by
      another batch of cathodic solution only when the pH reaches a very high value.
      The delivery rate of the ferrous iron should be maintained at an electrolytic
      current between 0.01 and 0.02 A; the ratio of H2O2/Fe2+ should be between 5:1 and
      10:1. NaCl was found to be the best electrolyte, with concentrations of 0.01-0.02
      and 0.08 M in the anodic and cathodic half-cells, respectively. The FAFT system
      was successfully applied to degrade various model amide compounds and DEET
      formulations, which suggests the likelihood of extending this approach to other
      pesticide-containing wastewaters.

PMID- 17439151
TI  - Weakening of salmonella with selected microbial metabolites of berry-derived
      phenolic compounds and organic acids.
AB  - Gram-negative bacteria are important food spoilage and pathogenic bacteria. Their
      unique outer membrane (OM) provides them with a hydrophilic surface structure,
      which makes them inherently resistant to many antimicrobial agents, thus
      hindering their control. However, with permeabilizers, compounds that
      disintegrate and weaken the OM, Gram-negative cells can be sensitized to several
      external agents. Although antimicrobial activity of plant-derived phenolic
      compounds has been widely reported, their mechanisms of action have not yet been
      well demonstrated. The aim of our study was to elucidate the role of selected
      colonic microbial metabolites of berry-derived phenolic compounds in the
      weakening of the Gram-negative OM. The effect of the agents on the OM
      permeability of Salmonella was studied utilizing a fluorescence probe uptake
      assay, sensitization to hydrophobic antibiotics, and lipopolysaccharide (LPS)
      release. Our results show that 3,4-dihydroxyphenylacetic acid, 3
      hydroxyphenylacetic acid, 3-(3,4-dihydroxyphenyl)propionic acid (3,4-diHPP), 3-(4
      hydroxyphenyl)propionic acid, 3-phenylpropionic acid, and 3-(3
      hydroxyphenyl)propionic acid efficiently destabilized the OM of Salmonella
      enterica subsp. enterica serovar Typhimurium and S. enterica subsp. enterica
      serovar Infantis as indicated by an increase in the uptake of the fluorescent
      probe 1-N-phenylnaphthylamine (NPN). The OM-destabilizing activity of the
      compounds was partially abolished by MgCl2 addition, indicating that part of
      their activity is based on removal of OM-stabilizing divalent cations.
      Furthermore, 3,4-dihydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, and 3,4
      diHPP increased the susceptibility of S. enterica subsp. enterica serovar
      Typhimurium strains for novobiocin. In addition, organic acids present in
      berries, such as malic acid, sorbic acid, and benzoic acid, were shown to be
      efficient permeabilizers of Salmonella as shown by an increase in the NPN uptake
      assay and by LPS release.

PMID- 17439152
TI  - Identification, characterization, epitope mapping, and three-dimensional modeling
      of the alpha-subunit of beta-conglycinin of soybean, a potential allergen for
      young pigs.
AB  - Soybean meal (SBM), the major byproduct of soybean oil extraction, is the main
      protein source for swine diets globally. In the United States, 8.6 million metric
      tons of SBM was used in swine rations in 2004. The pathological effect and
      immunological response of SBM feeding have been demonstrated in swine. In this
      study, we have utilized plasma collected from piglet feed with SBM in immunoblot
      analysis to detect proteins that elicited antigenic responses. We have identified
      soybean beta-conglycinin alpha-subunit as being a potential allergen for young
      piglets. Characterization of this protein indicated that deglycosylation and
      pepsin digestion did not eliminate immunoreactivity of this protein. Epitope
      mapping utilizing planar cellulose supports technology (SPOT) showed that three
      peptides spanning amino acids S185-R231 were critical for the allergenicity. A
      computer-generated three-dimensional structure model of the alpha-subunit of beta
      conglycinin indicated that the antigenic epitopes were located on the surface of
      the protein. Information from this study may assist in the construction of
      recombinant nonallergenic soybean protein useable for both immunotherapy and the
      potential production of hypoallergenic soybean plants.

PMID- 17439153
TI  - Genetic variability of carotenoid concentration and degree of esterification
      among tritordeum (xTritordeum Ascherson et Graebner) and durum wheat accessions.
AB  - The higher carotenoid content (commonly referred as "yellow pigment content") of
      tritordeum seeds as compared to wheat and the potential of this species as a
      donor of useful traits to wheat led us to investigate the detailed carotenoid
      composition of 53 accessions of hexaploid tritordeums originating from different
      stages of the tritordeum breeding program developed at IAS-CSIC. In addition,
      seven durum wheat accessions were also studied for comparison. Lutein was the
      unique carotenoid detected, either free or esterified with fatty acids. On
      average, tritordeum had 5.2 times more carotenoids than durum wheat, which
      suggests a high potential of this species to become a functional food. In
      addition, the most outstanding result of this work is the high esterification
      degree of lutein found in tritordeums as compared to durum wheat. This difference
      may indicate the differential esterification ability between tritordeum and durum
      wheat species. The implications of this high level of lutein esterification on
      both carotenoid accumulation and stability are discussed.

PMID- 17439154
TI  - Caspase activation by anticancer drugs: the caspase storm.
AB  - This study measures the time-dependence of cellular caspase activation by
      anticancer drugs and compares it with that of cellular respiration. Intracellular
      caspase activation and cellular respiration were measured during continuous
      exposure of Jurkat, HL-60, and HL-60/MX2 (deficient in topoisomerase-II) cells to
      dactinomycin, doxorubicin, and the platinum (Pt) compounds cisplatin,
      carboplatin, and oxaliplatin. Caspase activation was measured using the
      fluorogenic compound N-acetyl-asp-glu-val-asp-7-amino-4-trifluoromethyl coumarin
      (Ac-DEVD-AFC). We show that this substrate rapidly enters cells where it is
      efficiently cleaved at the aspartate residue by specific caspases, yielding the
      fluorescent compound 7-amino-4-trifluoromethyl coumarin (AFC). Following cell
      disruption, released AFC was separated on HPLC and detected by fluorescence. The
      appearance of AFC in cells was blocked by the pancaspase inhibitor
      benzyloxycarbonyl-val-ala-asp-fluoromethylketone, thus establishing that
      intracellular caspases were responsible for the cleavage. Caspase activity was
      first noted after about 2 h of incubation with doxorubicin or dactinomycin, the
      production of AFC being linear with time afterward. Caspase activation by
      doxorubicin was delayed in HL-60/MX2 cells, reflecting the critical role of
      topoisomerase-II in doxorubicin cytotoxicity. For both drugs, caspase activity
      increased rapidly between approximately 2 and approximately 6 h, went through a
      maximum, and decreased after approximately 8 h ("caspase storm"). Cisplatin
      treatment induced noticeable caspase activity only after approximately 14 h of
      incubation, and the fluorescent intensity of AFC became linear with time at
      approximately 16 h. Exposure of the cells to all of the drugs studied led to
      impaired cellular respiration and decreased cellular ATP, concomitant with
      caspase activation. Thus, the mitochondria are rapidly targeted by active
      caspases.

PMID- 17439155
TI  - Effect of feed and bleed rate on hybridoma cells in an acoustic perfusion
      bioreactor: metabolic analysis.
AB  - For the development of optimal perfusion processes, insight into the effect of
      feed and bleed rate on cell growth, productivity, and metabolism is essential. In
      the here presented study the effect of the feed and bleed rate on cell metabolism
      was investigated using metabolic flux analysis. Under all tested feed and bleed
      rates the biomass concentration as calculated from the nitrogen balance (biomass
      nitrogen) increased linearly with an increase in feed rate, as would be expected.
      However, depending on the size of the feed and bleed rate, this increase was
      attained in two different ways. At low feed and bleed rates (Region I) the
      increase was obtained through an increase in viable-cell concentration, while the
      cellular-nitrogen content remained constant. At high feed and bleed rates (Region
      II) the increase was attained through an increase in cellular-nitrogen content,
      while the cell concentration remained constant. Per gram biomass-nitrogen, the
      specific consumption and production rates of the majority of the nutrients and
      products were identical in both regions, as were most of the fluxes. The major
      difference between the two regions was an increased flux from pyruvate to lactate
      and a decreased flux of pyruvate toward citrate in region II. The decreased in
      flux at the level of citrate can either be balanced by a decreased out-flux
      toward lipid biosynthesis leading to a lower fraction of lipids in the cell, by a
      decreased out-flux toward the citric acid cycle resulting in a decreased energy
      generation, or by a combination of these. Finally, the specific productivity
      increases less than the nitrogen content per cell in region II, which implies
      that for obtaining maximum production rates it is important to increase the cell
      density and not only the biomass density.

PMID- 17439156
TI  - Molecular dynamics simulations to investigate the domain swapping mechanism of
      human cystatin C.
AB  - Human cystatin C (HCC), one of the amyloidgenic proteins, has been proved to form
      a dimeric structure via a domain swapping process and then cause amyloid deposits
      in the brains of patients suffering from Alzheimer's disease. HCC monomer
      consists of a core with a five-stranded antiparallel beta-sheet (beta region)
      wrapped around a central helix. The connectivity of these secondary structures
      is: (N)-beta1-alpha-beta2-L1-beta3-AS-beta4-L2-beta5-(C). In this study, various
      molecular dynamics simulations were conducted to investigate the conformational
      changes of the monomeric HCC at different temperatures (300 and 500 K) and pH
      levels (2, 4, and 7) to gain insight into the domain swapping mechanism. The
      results show that high temperature (500 K) and low pH (pH 2) will trigger the
      domain swapping process of HCC. We further proposed that the domain swapping
      mechanism of HCC follows four steps: (1) the alpha-helix moves away from the beta
      region; (2) the contacts between beta2 and beta3-AS disappear; (3) the beta2-L1
      beta3 hairpin unfolds following the so-called "zip-up" mechanism; and finally (4)
      the HCC dimer is formed. Our study shows that high temperature can accelerate the
      unfolding of HCC and the departure of the alpha-helix from the beta-region,
      especially at low pH value. This is attributed to the fact that that low pH
      results in the protonation of the side chains of Asp, Glu, and His residues,
      which further disrupts the following four salt-bridge interactions stabilizing
      the alpha-beta interface of the native structure: Asp15-Arg53 (beta1-beta2),
      Glu21/20-Lys54 (helix-beta2), Asp40-Arg70 (helix-AS), and His43-Asp81 (beta2-AS).

PMID- 17439157
TI  - From peptide to protein: comparative analysis of the substrate specificity of N
      linked glycosylation in C. jejuni.
AB  - The gram-negative bacterium Campylobacter jejuni was recently discovered to
      contain a general N-linked protein glycosylation pathway. Central to this pathway
      is PglB, a homologue of the Stt3p subunit of the eukaryotic oligosaccharyl
      transferase (OT), which is involved in the transfer of an oligosaccharide from a
      polyisoprenyl pyrophosphate carrier to the asparagine side chain of proteins
      within the conserved glycosylation sites D/E-X1-N-X2-S/T, where X1 and X2 can be
      any amino acids except proline. Using a library of peptide substrates and a
      quantitative radioactivity-based in vitro assay, we assessed the amino acids at
      each position of the consensus glycosylation sequence for their impact on
      glycosylation efficiency, whereby the sequence DQNAT was found to be the optimal
      acceptor substrate. In the context of a full-length folded protein, the
      differences between variations of the glycosylation sequences were found to be
      consistent with the trends observed from their peptidyl counterparts, though less
      dramatic because of additional influences. In addition to characterizing the
      acceptor preferences of PglB, we also assessed the selectivity toward the glycan
      donor. Interestingly, despite recent reports of relaxed selectivity toward the
      glycan donor, PglB was not found to be capable of utilizing glycosyl donors such
      as dolichyl-pyrophosphate-chitobiose, which is the minimum substrate for the
      eukaryotic OT process.

PMID- 17439158
TI  - Green fluorescent protein ground states: the influence of a second protonation
      site near the chromophore.
AB  - The photophysical properties of most green fluorescent protein mutants (GFPs) are
      strongly affected by pH. This effect must be carefully taken into account when
      using GFPs as fluorescent probes or indicators. Usually, the pH-dependence of
      GFPs is rationalized on the basis of the ionization equilibrium of the
      chromophore phenol group. Yet many different mutants show spectral behavior that
      cannot be explained by ionization of this group alone. In this study, we propose
      a general model of protonation comprising two ionization sites (2S model). Steady
      state optical measurements at different pH and temperature and pH-jump relaxation
      experiments were combined to highlight the thermodynamic and kinetic properties
      of paradigmatically different GFP variants. Our experiments support the 2S model.
      For the case of mutants in which E222 is the second protonation site,
      thermodynamic coupling between this residue's and the chromophore's ionization
      reactions was demonstrated. In agreement with the 2S model predictions, X-ray
      analysis of one of these mutants showed the presence of two chromophore
      populations at high pH.

PMID- 17439159
TI  - Fluorescence quenching by nucleotides of the plasma membrane H+-ATPase from
      Kluyveromyces lactis.
AB  - The yeast plasma membrane H+-ATPase isolation procedure was improved; a highly
      pure enzyme (90-95%) was obtained after centrifugation on a trehalose
      concentration gradient. H+-ATPase kinetics was slightly cooperative: Hill number
      = 1.5, S0.5 = 800 microM ATP, and turnover number = 36 s-1. In contrast to those
      of other P-type ATPases, H+-ATPase fluorescence was highly sensitive to
      nucleotide binding; the fluorescence decreased 60% in the presence of both 5 mM
      ADP and AMP-PNP. Fluorescence titration with nucleotides allowed calculation of
      dissociation constants (Kd) from the binding site; Kd values for ATP and ADP were
      700 and 800 microM, respectively. On the basis of amino acid sequence and
      homology model analysis, we propose that binding of the nucleotide to the N
      domain is coupled to the movement of a loop beta structure and to the exposure of
      the Trp505 residue located in the loop. The recombinant N-domain also displayed a
      large hyperbolic fluorescence quenching when ATP binds; however, it displayed a
      higher affinity for ATP (Kd = 100 microM). We propose for P-type ATPases that
      structural movements during nucleotide binding could be followed if a Trp residue
      is properly located in the N-domain. Further, we propose the use of trehalose in
      enzyme purification protocols to increase the purity and quality of the isolated
      protein and to perform structural studies.

PMID- 17439161
TI  - Protein-derived cofactors. Expanding the scope of post-translational
      modifications.
AB  - Recent advances in enzymology, structural biology, and protein chemistry have
      extended the scope of the field of cofactor-dependent enzyme catalysis. It has
      been documented that catalytic and redox-active prosthetic groups may be derived
      from post-translational modification of amino acid residues of proteins. These
      protein-derived cofactors typically arise from the oxygenation of aromatic
      residues, covalent cross-linking of amino acid residues, or cyclization or
      cleavage of internal amino acid residues. In some cases, the post-translation
      modification is a self-processing event, whereas in others, another processing
      enzyme is required. The characterization of protein-derived cofactors and their
      mechanisms of biogenesis introduce a new dimension to our current views about
      protein evolution and protein structure-function relationships.

PMID- 17439160
TI  - A remote substrate docking mechanism for the tec family tyrosine kinases.
AB  - During T cell signaling, Itk selectively phosphorylates a tyrosine within its own
      SH3 domain and a tyrosine within PLCgamma1. We find that the remote SH2 domain in
      each of these substrates is required to achieve efficient tyrosine
      phosphorylation by Itk and extend this observation to two other Tec family
      kinases, Btk and Tec. Additionally, we detect a stable interaction between the
      substrate SH2 domains and the kinase domain of Itk and find that addition of
      specific, exogenous SH2 domains to the in vitro kinase assay competes directly
      with substrate phosphorylation. On the basis of these results, we show that the
      kinetic parameters of a generic peptide substrate of Itk are significantly
      improved via fusion of the peptide substrate to the SH2 domain of PLCgamma1. This
      work is the first characterization of a substrate docking mechanism for the Tec
      kinases and provides evidence of a novel, phosphotyrosine-independent regulatory
      role for the ubiquitous SH2 domain.

PMID- 17439162
TI  - Phase behavior of aqueous suspensions of Mg(2)Al layered double hydroxide: the
      competition among nematic ordering, sedimentation, and gelation.
AB  - Birefringence observations and rheological measurements were used to monitor the
      phase behavior of Mg/Al (the molar ratio of Mg(2+) to Al(3+) being 2:1) layered
      double hydroxide (LDH) suspensions. The suspensions of concentration lower than
      16% (w/w) appear isotropic (I) between crossed polarizers. In contrast, the
      suspensions of concentration between 16% and 30% (w/w) showed an isotropic (I)
      nematic (N) biphasic coexistence. Detailed observations led us to divide the
      suspensions in the gap into three groups according to their behaviors: the
      suspensions with concentration between 16% and 25% (w/w) experienced an I-N phase
      transition and particle sedimentation simultaneously, while the suspensions of
      25% to 27% (w/w) showed I-N transition after particle sedimentation, and in the
      suspension of 30% (w/w), a critical sol-gel transition appeared with an I-N
      transition. Above 33% (w/w), the gel network hindered a complete I-N separation
      in the suspensions. Upon raising the NaCl concentration, the liquid crystalline
      phase transition and the sol-gel transition shifted to higher particle
      concentrations. The facts demonstrate that the phase behavior of aqueous LDH
      suspensions is controlled by the competition among liquid crystal phase
      transition, sedimentation, and gelation.

PMID- 17439163
TI  - Viscoelasticity of a nonionic lamellar phase.
AB  - The linear viscoelastic properties of a nonionic lamellar phase in C-orientation
      were studied as a function of temperature by small-amplitude oscillatory
      measurements in the frequency range 0.5-5 Hz. An almost solid-like elastic
      response was observed at all studied temperatures, from 42 to 20 degrees C. In
      this range, the elastic modulus was found to increase strongly with decreasing
      temperature. The elasticity is attributed to screw dislocations connecting layers
      in the stack, and the data thus suggest that the density of screw dislocations
      decreases with increasing temperature. The lamellar phase forms an "onion"
      texture when continuously sheared at lower temperatures. It is argued that a
      possible origin for the shear-induced "onion" texture is the instability of the
      screw dislocations in shear flow. By 2H NMR experimentation, we also find the
      formation of a random mesh phase at lower temperatures. The presence of
      equilibrium bilayer perforations, however, does not correlate with the "onion"
      stability.

PMID- 17439164
TI  - Viscoelastic micellar solutions in a mixed nonionic fluorinated surfactants
      system and the effect of oils.
AB  - Formation and rheological behavior of viscoelastic wormlike micelles in aqueous
      solution of a mixed system of nonionic fluorinated surfactants, perfluoroalkyl
      sulfonamide ethoxylate, C8F17SO2N(C3H7)(CH2CH2O)nH (abbreviated as C8F17EOn) was
      studied. In the water-surfactant binary system C8F17EO20 forms an isotropic
      micellar solution over wide concentration range (>85 wt %) at 25 degrees C. With
      successive addition of C8F17EO1 to the aqueous C8F17EO20 solution, viscosity of
      the solution increases swiftly, and a viscoelastic solution is formed. The
      oscillatory rheological behavior of the viscoelastic solution can be described by
      Maxwell model at low-frequency region, which is typical of wormlike micelles.
      With further addition of C8F17EO1, the viscosity decreases after a maximum and
      phase separation occurs. Addition of a small amount of fluorinated oils to the
      wormlike micellar solution disrupts the network structure and decreases the
      viscosity sharply. It is found that polymeric oil, PFP (F-(C3F6O)nCF2CF2COOH),
      decreases the viscosity more effectively than the perfluorodecalin (PFD). The
      difference in the effect of oil on rheological properties is explained in terms
      of the solubilization site of the oils in the hydrophobic interior of the
      cylindrical aggregates, and their ability to induce rod-sphere transition.

PMID- 17439165
TI  - A hierarchical self-assembly route to three-dimensional polymer-quantum dot
      photonic arrays.
AB  - We demonstrate a new hierarchical self-assembly strategy for the formation of
      photonic arrays containing quantum dots (QDs), in which sequential self-assembly
      steps introduce organization on progressively longer length scales, ranging from
      the nanoscale to the microscale regimes. The first step in this approach is the
      self-assembly of diblock copolymers to form block ionomer reverse micelles (SA1);
      within each micelle core, a single CdS QD is synthesized to yield the hybrid
      building block BC-QD. Once SA1 is completed, the hydrophobic BD-QD building
      blocks are blended with amphiphilic block copolymer stabilizing chains in an
      organic solvent; water addition induces secondary self-assembly (SA2) to form
      quantum dot compound micelles (QDCMs). Finally, aqueous dispersions of QDCMs are
      slowly evaporated to induce the formation of three-dimensional (3D) close-packed
      arrays in a tertiary self-assembly step (SA3). The resulting hierarchical
      assemblies, consisting of a periodic array of hybrid spheres each containing
      multiple CdS QDs, exhibit the collective property of a photonic stop band, along
      with photoluminescence arising from the constituent QDs. A high degree of
      structural control is possible at each level of organization by judicious
      selection of experimental variables, allowing various parameters governing the
      collective optical properties, including QD size, nanoparticle spacing, and
      mesocale periodicity, to be independently tuned. The resulting control over
      optical properties via successive self-assembly steps should provide new
      opportunities for hierarchical materials for QD lasers and all-optical switching.

PMID- 17439167
TI  - Folding of the 25 residue Abeta(12-36) peptide in TFE/water: temperature
      dependent transition from a funneled free-energy landscape to a rugged one.
AB  - The free-energy landscape of the Alzheimer beta-amyloid peptide Abeta(12-36) in a
      40% (v/v) 2,2,2-trifluoroethanol (TFE)/water solution was determined by using
      multicanonical molecular dynamics simulations. Simulations using this enhanced
      conformational sampling technique were initiated from a random unfolded
      polypeptide conformation. Our simulations reliably folded the peptide to the
      experimental NMR structure, which consists of two linked helices. The shape of
      the free energy landscape for folding was found to be strongly dependent on
      temperature: Above 325 K, the overall shape was funnel-like, with the bottom of
      the funnel coinciding exactly with the NMR structure. Below 325 K, on the other
      hand, the landscape became increasingly rugged, with the emergence of new
      conformational clusters connected by low free-energy pathways. Finally, our
      simulations reveal that water and TFE solvate the polypeptide in different ways:
      The hydrogen bond formation between TFE and Abeta was enhanced with decreasing
      temperature, while that between water and Abeta was depressed.

PMID- 17439166
TI  - An experimentally derived database of candidate Ras-interacting proteins.
AB  - We used a TAP-tag approach to identify candidate binding proteins for the related
      Ras family GTPases: H-Ras, R-Ras, and Rap1A. Protein complexes were isolated from
      mouse fibroblasts, and component proteins were identified by a combination of
      nanoflow HPLC and tandem mass spectrometry. H-Ras was found to associate with
      numerous cytoskeletal proteins including talin-1. R-Ras and Rap1A each associated
      with various signaling molecules, many of which are membrane-associated. Thus, we
      have established the first database of potential Ras interactors in mammalian
      cells.

PMID- 17439168
TI  - Unusual spin transition behavior in 2,6-bis((pyrazol-3-yl)-pyridine) iron(II)-bis
      oxalato-platinate(II).
AB  - [Fe(bpp)2][Pt(ox)2].H2O (with bpp=2,6-bis(pyrazol-3-yl)-pyridine and ox=oxalate)
      was prepared, and its spin crossover behavior was characterized. The two-step
      spin transition behavior changes over several cycles. The original behavior is
      restored when the sample is allowed to relax for a week. Furthermore, the ST
      exhibits a strong dependence on the heating and cooling rate. Heating the
      compound at 1 K/min leads to a spin transition with a third step and a second
      plateau at gammaHS approximately 0.8. Quenching the sample to 77 K also affects
      the spin transition behavior. The kinetic relaxation is followed after quenching
      and after light-induced excited spin state trapping experiments.

PMID- 17439169
TI  - Replica exchange with solute tempering: efficiency in large scale systems.
AB  - We apply the recently developed replica exchange with solute tempering (REST) to
      three large solvated peptide systems: an alpha-helix, a beta-hairpin, and a
      TrpCage, with these peptides defined as the "central group". We find that our
      original implementation of REST is not always more efficient than the replica
      exchange method (REM). Specifically, we find that exchanges between folded (F)
      and unfolded (U) conformations with vastly different structural energies are
      greatly reduced by the nonappearance of the water self-interaction energy in the
      replica exchange acceptance probabilities. REST, however, is expected to remain
      useful for a large class of systems for which the energy gap between the two
      states is not large, such as weakly bound protein-ligand complexes.
      Alternatively, a shell of water molecules can be incorporated into the central
      group, as discussed in the original paper.

PMID- 17439170
TI  - Multichromophoric Forster resonance energy transfer from b800 to b850 in the
      light harvesting complex 2: evidence for subtle energetic optimization by purple
      bacteria.
AB  - This work provides a detailed account of the application of our multichromophoric
      Forster resonance energy transfer (MC-FRET) theory (Phys. Rev. Lett. 2004, 92,
      218301) for the calculation of the energy transfer rate from the B800 unit to the
      B850 unit in the light harvesting complex 2 (LH2) of purple bacteria. The model
      Hamiltonian consists of the B800 unit represented by a single bacteriochlorophyll
      (BChl), the B850 unit represented by its entire set of BChls, the electronic
      coupling between the two units, and the bath terms representing all environmental
      degrees of freedom. The model parameters are determined, independent of the rate
      calculation, from the literature data and by a fitting to an ensemble line shape.
      Comparing our theoretical rate and a low-temperature experimental rate, we
      estimate the magnitude of the BChl-Qy transition dipole to be in the range of 6.5
      7.5 D, assuming that the optical dielectric constant of the medium is in the
      range of 1.5-2. We examine how the bias of the average excitation energy of the
      B800-BChl relative to that of the B850-BChl affects the energy transfer time by
      calculating the transfer rates based on both our MC-FRET theory and the original
      FRET theory, varying the value of the bias. Within our model, we find that the
      value of bias 260 cm-1, which we determine from the fitting to an ensemble line
      shape, is very close to the value at which the ratio between MC-FRET and FRET
      rates is a maximum. This provides evidence that the bacterial system utilizes the
      quantum mechanical coherence among the multiple chromophores within the B850 in a
      constructive way so as to achieve efficient energy transfer from B800 to B850.

PMID- 17439171
TI  - Fabrication of "tadpole"-like magnetite/multiwalled carbon nanotube
      heterojunctions and their self-assembly under external magnetic field.
AB  - Novel "tadpole"-like Fe3O4/multiwalled carbon nanotube (MWCNT) heterojunctions
      were successfully synthesized by position-selectively attaching Fe3O4 sphere on
      the tips of MWCNTs through a straightforward and effective polyol-medium
      solvothermal method. Transmission and scanning electron microscopy (TEM and SEM)
      and X-ray diffraction (XRD) investigations show these Fe3O4 spheres are
      constructed with tiny nanocrystallites (approximately 5 nm in average diameter),
      which were preferentially aggregated in an oriented pattern on the open ends of
      the MWCNT template. Magnetic investigation indicates this novel Fe3O4/MWCNT
      hybrid presents superparamagnetic behavior. The size and corresponding magnetic
      performance of these magnetite/MWCNT hybrids can be adjustable to some extent for
      specific applications through altering the reaction parameters. Furthermore,
      these tadpolelike nanocomposites can orient and self-assemble into one
      dimensional structure under external magnetic field, displaying great potential
      in precise manipulation and organization of carbon nanotube-based structures into
      integrated functional system.

PMID- 17439172
TI  - Interaction of urea with pluronic block copolymers by 1H NMR spectroscopy.
AB  - Solution 1H NMR techniques were used to characterize the interaction of urea with
      poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO)
      triblock copolymers. The urea was established to interact selectively with the
      PEO blocks of the block copolymer, and the interaction sites were found not to
      change with increasing temperature. Such interactions influence the self-assembly
      properties of the block copolymer in solution by increasing the hydration of the
      block copolymers and stabilizing the gauche conformation of the PPO chain.
      Therefore, urea increases the critical micellization temperature (CMT) values of
      PEO-PPO-PEO copolymers, and the effect of urea on the CMT is more pronounced for
      copolymers with higher PEO contents and lower for those with increased contents
      of PPO segments.

PMID- 17439175
TI  - Perfluoroalkylated 4,13-diaza-18-crown-6 ethers: synthesis, phase-transfer
      catalysis, and recycling studies.
AB  - A series of N,N'-dialkyl-4,13-diaza-18-crown-6 lariat ethers possessing two C8H17
      (2), (CH2)3C8F17 (3), (CH2)3C10F21 (4), and (CH2)2C8F17 (5) side arms were
      synthesized in good yields by N-alkylation of 4,13-diaza-18-crown-6. Potassium
      picrate could be extracted from an aqueous solution into an organic phase by all
      of the perfluoroalkylated macrocycles demonstrating their potential to be used as
      phase-transfer catalysts, and preliminary studies on a classical nucleophilic
      substitution established that they each gave higher catalytic activities under
      solid-liquid than under liquid-liquid phase-transfer conditions. The light
      fluorous macrocycles gave similar, if not better, catalytic activity compared to
      the parent, non-fluorinated phase-transfer catalyst 2 under solid-liquid
      conditions in conventional organic solvents in both an aliphatic and an aromatic
      nucleophilic substitution. N,N'-Bis(1H,1H,2H,2H,3H,3H-perfluoroundecyl)-4,13
      diaza-18-crown-6 (3) was recycled six times in the iodide displacement reaction
      of 1-bromooctane and four times in the fluoride displacement reaction of 2,4
      dinitrochlorobenzene using fluorous solid-phase extraction without any loss in
      activity.

PMID- 17439174
TI  - The synthesis and inhibitory activity of dethiotrypanothione and analogues
      against trypanothione reductase.
AB  - Trypanothione reductase (TR) catalyzes the NADPH-dependent reduction of
      trypanothione disulfide (1). TR plays a central role in the trypanosomatid
      parasite's defense against oxidative stress and has emerged as a promising target
      for antitrypanosomal drugs. We describe the synthesis and activity of
      dethiotrypanothione and analogues (2-4) as inhibitors of Trypanosoma cruzi TR.
      The syntheses of these macrocycles feature ring-closing olefin metathesis (RCM)
      reactions catalyzed by ruthenium catalyst 17. Derivative 4 is our most potent
      inhibitor with a Ki=16 microM.

PMID- 17439173
TI  - Viral inhibition studies on sulfated lignin, a chemically modified biopolymer and
      a potential mimic of heparan sulfate.

PMID- 17439176
TI  - Reducing power of simple polyphenols by electron-transfer reactions using a new
      stable radical of the PTM series, tris(2,3,5,6-tetrachloro-4-nitrophenyl)methyl
      radical.
AB  - The synthesis and characterization of a new radical and its use for testing the
      antioxidant activity of polyphenols by electron transfer are reported. This new
      and stable species of magnetic nature, tris(2,3,5,6-tetrachloro-4
      nitrophenyl)methyl (TNPTM) radical, has been characterized by electron
      paramagnetic resonance and its molecular structure determined by X-ray analysis.
      This new radical of the PTM (perchlorotriphenylmethyl) series, unlike 2,2
      diphenyl-1-picrylhydrazyl (DPPH) radical, is stable in conditions of hydrogen
      abstraction reactions. TNPTM radical is able to discriminate between the
      antioxidant activities of catechol and pyrogallol in hydroxylated solvent
      mixtures such as chloroform/methanol (2:1). These features determine the
      antioxidant/pro-oxidant character and the biological activities of natural and
      synthetic flavonoids.

PMID- 17439178
TI  - Solid-phase synthesis of N-nosyl- and N-Fmoc-N-methyl-alpha-amino acids.
AB  - We report here a convenient and simple solid-phase synthesis of N-nosyl-N-methyl
      alpha-amino acids and N-Fmoc-N-methyl-alpha-amino acids, important building
      blocks for the synthesis of conformationally restricted and protease-resistant
      natural peptides and peptide analogues. The methodology involves the use of 2
      chlorotrityl chloride resin to temporarily protect the carboxylic group of alpha
      amino acids and of diazomethane as the reagent to methylate the sulfonamidic
      function. The approach developed is particularly efficient also with alpha-amino
      acids bearing appropriately protected functionalized side chains.

PMID- 17439177
TI  - Studies on the intramolecular cyclizations of bicyclic delta-hydroxynitriles
      promoted by triflic anhydride.
AB  - Studies have been conducted to investigate the reactivity of several bicyclic
      delta-hydroxynitriles with triflic anhydride in dichloromethane. The reactions of
      the analogues derived from 1-indanone and 1-tetralone lead to annulated enones.
      These products arise from an initial elimination reaction that generates an
      alkene, followed by the addition of the carbon-carbon double bond to the
      activated cyano group. The intramolecular cyclization of the derivative obtained
      from 1-benzosuberone unexpectedly followed a different path, giving a cyclic
      imidate as the major product. In this case, the activated cyano group is directly
      attacked by the hydroxyl group of the starting delta-hydroxynitrile. Theoretical
      calculations provide a rationale for the observed reactivity pattern. Both the
      formation of the triflate via its protonated form, its subsequent ionization to
      the carbocation, and the cyclization of the resulting alkene to the enone become
      less favorable when the size of the ring increases due to conformational effects.
      The opposite trend is observed for the competing Pinner-type cyclization to the
      imidate. An alternative mechanism for the formation of the lactams from the
      cyclic imidates under acid-catalyzed conditions has also been proposed.

PMID- 17439179
TI  - Facile synthesis of Janus "double-concave" tribenzo[a,g,m]coronenes.
AB  - Hexabutoxytribenzo[a,g,m]coronenes have been prepared in three steps from readily
      accessible hexabutoxytriphenylene. Single-crystal X-ray diffraction analysis
      reveals that these molecules can adopt an extraordinary "double-concave"
      conformation that makes them ideal hosts for the binding of different guest
      molecules at each face.

PMID- 17439180
TI  - A new unusual natural pigment from Selaginella sinensis and its noticeable
      physicochemical properties.
AB  - A new unusual pigment with a novel carbon framework named selaginellin (1) was
      isolated from the acetone extract of Selaginella sinensis, and its methoxy
      derivative (1a) was synthesized. Both selaginellin 1 and 1a are racemic
      compounds. The structure of selaginellin 1 was established as (R,S)-4-[(4'
      hydroxy-4-(hydroxymethyl)-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4
      hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one and 1a as (R,S)-4-[(4'-methoxy-4
      (methoxymethyl)-3-((4-methoxyphenyl)ethynyl)biphenyl-2-yl)(4
      methoxyphenyl)methylene]-2,5-cyclohexadien-1-one by the analysis of one- and two
      dimensional NMR data, HR-ESIMS, EI-MS, IR, UV, CD, and single-crystal X-ray
      experiments, and the mechanism of their color change according to different pH
      values and fluorescent properties was studied.

PMID- 17439181
TI  - A highly stereoselective synthesis of (-)-(ent)-julifloridine from the
      cyclization of an alanine-derived chloroamine with an acetylenic sulfone.
AB  - The cyclization of gamma-chloroamine 11, derived from l-alanine, and acetylenic
      sulfone 12 afforded the dehydropiperidine 19 via conjugate addition followed by
      intramolecular alkylation of the corresponding sulfone-stabilized anion. An
      unexpected acid-catalyzed desulfonylation of 19 occurred in one step via
      desilylation and tautomerization of the enamine moiety to the corresponding
      aldehyde, followed by elimination of p-toluenesulfinic acid. The highly
      stereoselective reduction of the resulting unsaturated aldehyde 25 with sodium
      cyanoborohydride produced piperidine 23 with a diastereomeric ratio of >98:2. (-)
      (ent)-Julifloridine (8) was obtained by Swern oxidation of 23, followed by Wittig
      olefination and hydrogenation/debenzylation.

PMID- 17439182
TI  - Probing molecular shape. 1. Conformational studies of 5
      hydroxyhexahydropyrimidine and related compounds.
AB  - Understanding the factors that determine molecular shape enables scientists to
      begin to understand and tailor molecular properties and reactivity. Many
      biomolecules and bioactive compounds contain aliphatic heterocyclic rings whose
      conformations play a major role in their biological activity. The interplay of a
      number of factors, both steric and electronic, is examined for 5
      hydroxyhexahydropyrimidine (1) and related compounds with use of spectroscopy and
      molecular modeling.

PMID- 17439183
TI  - Chemotherapeutic interventions targeting HIV interactions with host-associated
      carbohydrates.

PMID- 17439184
TI  - Reactions of C-H bonds in water.

PMID- 17439185
TI  - Spontaneous stretching of DNA in a two-dimensional nanoslit.
AB  - DNA molecules in silicon dioxide-glass fluidic nanoslits spontaneously extend at
      the lateral sidewalls of the slit. The nanoslit geometry, however, physically
      confines polymer molecules to two spatial dimensions; further reduction in
      configurational entropy resulting in axially stretched molecules arises
      spontaneously and appears to be electrostatically mediated. The observations not
      only shed light on electrostatic interactions of charged soft matter with like
      charged confining walls but also offer a new method to stretch DNA in solution.

PMID- 17439186
TI  - Sub-10 nm device fabrication in a transmission electron microscope.
AB  - We show that a high-resolution transmission electron microscope can be used to
      fabricate metal nanostructures and devices on insulating membranes by
      nanosculpting metal films. Fabricated devices include nanogaps, nanodiscs,
      nanorings, nanochannels, and nanowires with tailored curvatures and multi
      terminal nanogap devices with nanoislands or nanoholes between the terminals. The
      high resolution, geometrical flexibility, and yield make this fabrication method
      attractive for many applications including nanoelectronics and nanofluidics.

PMID- 17439187
TI  - Plasmonic nanosensors for imaging intracellular biomarkers in live cells.
AB  - Here we present the first intracellular molecular imaging platform using
      multifunctional gold nanoparticles which incorporate both cytosolic delivery and
      targeting moieties on the same particle. The utility of these intracellular
      sensors was demonstrated by monitoring actin rearrangement in live fibroblasts.
      We observed a strong molecular specific optical signal associated with effective
      targeting of actin filaments. These multifunctional nanosensors can be adapted to
      target various intracellular processes especially where transfection or cytotoxic
      labels are not feasible.

PMID- 17439188
TI  - Buckling of lipid tubules in shrinking liquid droplets.
AB  - Self-assembled hollow lipid tubules are interesting and potentially useful
      supramolecular structures. Here, we study the deformation of lipid tubules of 1,2
      bis(tricosa-10,12-diynoyl)-sn-glycero-3-phosphocholine (DC8,9PC) trapped inside
      liquid droplets on glass substrates. The interface tension of the shrinking
      liquid droplets exerts a compression force on the ends of the trapped lipid
      tubules, and causes them to buckle. This provides a method to measure their
      mechanical properties. The Young's modulus of the DC8,9PC lipid tubules is
      estimated to approximately 1.07 GPa. As the strain energy of the buckled tubules
      builds up, they poke through the interface of shrinking liquid droplets and then
      adhere onto glass substrates to form looplike shapes.

PMID- 17439189
TI  - Manipulating the crystalline state of pharmaceuticals by nanoconfinement.
AB  - We show that nanoconfinement is a handle to rationally produce and stabilize
      otherwise metastable or transient polymorphs of pharmaceuticals, as required for
      controllable and efficient drug delivery. The systematic investigation of
      crystallization under confinement unveils thermodynamic properties of metastable
      polymorphs not accessible otherwise and may enhance the understanding of the
      crystallization behavior of pharmaceuticals in general. As an example in this
      case, we studied acetaminophen confined to inexpensive and biocompatible
      nanoporous host systems. Calorimetric and X-ray scattering data clearly evidence
      that either the stable polymorph form I or the metastable polymorph form III can
      be stabilized in high yields. Thermodynamic parameters for form III of
      acetaminophen are reported, and strategies to manipulate the crystalline state in
      pores by thermal treatments are presented.

PMID- 17439190
TI  - Nanodimensional organostannoxane molecular assemblies.
AB  - Organooxotin cages, clusters, and coordination polymers containing [Sn 2(mu-O)],
      [Sn 2(mu-OH)], [Sn 2(mu-O) 2], [Sn 2(mu-OH) 2], and [Sn 3(mu 3-O)(mu-OR) 3]
      building blocks have been assembled by the reactions of organotin precursors with
      phosphonic, phosphinic, carboxylic, or sulfonic acids. Various synthetic
      methodologies including Sn-C bond cleavage reactions and solventless procedures
      have been utilized to generate several nanodimensional organostannoxane
      assemblies. The synthesis, structure, and structural interrelationship of these
      diverse organostannoxane compounds are discussed. The synthetic knowledge gained
      to prepare specific organostannoxane structural forms in high yields has been
      utilized for the construction of dendrimer-like molecules. These contain a
      central stannoxane core and a functional periphery. The functional periphery can
      be readily modulated to assemble photoactive, electroactive, or multisite
      coordinating molecules. The synthesis, structure, and potential uses of these
      compounds are discussed.

PMID- 17439191
TI  - Anion binding involving pi-acidic heteroaromatic rings.
AB  - Anions are essential species in biological systems and, particularly, in enzyme
      substrate recognition. Therefore, the design and preparation of anion receptors
      is a topical field of supramolecular chemistry. Most host-guest systems
      successfully developed are based on noncovalent (ionic and hydrogen-bonded)
      interactions between anions and ammonium-type functionalities or Lewis acid
      groups. However, since the past 5 years, an alternative route toward the
      synthesis of efficient anion hosts has emerged, namely, the use of "anion-pi"
      interactions involving nitrogen-containing electron-deficient aromatic rings, as
      the result of several favorable theoretical investigations. In this Account, the
      state of the (new) art in this growing area of anion-binding research is
      presented and several selected examples from our work and that of other groups
      will be discussed.

PMID- 17439192
TI  - Measurements and automated mechanism generation modeling of OH production in
      photolytically initiated oxidation of the neopentyl radical.
AB  - Production of OH in the reaction of the neopentyl radical with O2 has been
      measured by a laser photolysis/cw absorption method for various pressures and
      oxygen concentrations at 673, 700, and 725 K. The MIT Reaction Mechanism
      Generator (RMG) was used to automatically generate a model for this system, and
      the predicted OH concentration profiles are compared to present and literature
      experimental results. Several reactions significantly affect the OH profile. The
      experimental data provide useful constraints on the rate coefficient for the
      formally direct chemical activation reaction of neopentyl radical with O2 to form
      OH (CH3)3CCH2 + O2 --> OH + 3,3-dimethyloxetane (Rxn 1) At 673 K and 60 Torr, log
      k(1) (cm(3) molecule(-1) s(-1)) = -13.7 +/- 0.5. Absolute absorbance measurements
      on OH and I indicate that the branching ratio for R + O2 to OH is about 0.03
      under these conditions. The data suggest that the ab initio neopentyl + O2
      potential energy surface of Sun and Bozzelli is accurate to within 2 kcal mol(
      1).

PMID- 17439193
TI  - Noncovalent interactions of Cu+ with N-donor ligands (pyridine, 4,4-dipyridyl,
      2,2-dipyridyl, and 1,10-phenanthroline): collision-induced dissociation and
      theoretical studies.
AB  - Collision-induced dissociation of complexes of Cu+ bound to a variety of N-donor
      ligands (N-L) with Xe is studied using guided ion beam tandem mass spectrometry.
      The N-L ligands examined include pyridine, 4,4-dipyridyl, 2,2-dipyridyl, and 1,10
      phenanthroline. In all cases, the primary and lowest-energy dissociation channel
      observed corresponds to the endothermic loss of a single intact N-L ligand.
      Sequential dissociation of additional N-L ligands is observed at elevated
      energies for the pyridine and 4,4-dipyridyl complexes containing more than one
      ligand. Ligand exchange processes to produce Cu+Xe are also observed as minor
      reaction pathways in several systems. The primary cross section thresholds are
      interpreted to yield 0 and 298 K bond dissociation energies (BDEs) after
      accounting for the effects of multiple ion-neutral collisions, the kinetic and
      internal energy distributions of the reactants, and dissociation lifetimes.
      Density functional theory calculations at the B3LYP/6-31G* level are performed to
      obtain model structures, vibrational frequencies, and rotational constants for
      the neutral N-L ligands and the Cu+(N-L)x complexes. The relative stabilities of
      the various conformations of these N-L ligands and Cu+(N-L)x complexes as well as
      theoretical BDEs are determined from single point energy calculations at the
      B3LYP/6-311+G(2d,2p) level of theory using B3LYP/6-31G* optimized geometries.
      Excellent agreement between theory and experiment is observed for all complexes
      containing one or two N-L ligands, while theory systematically underestimates the
      strength of binding for complexes containing more than two N-L ligands. The
      ground-state structures of these complexes and the trends in the sequential BDEs
      are explained in terms of stabilization gained from sd-hybridization and
      repulsive ligand-ligand interactions. The nature of the binding interactions in
      the Cu+(N-L)x complexes are examined via natural bond orbital analyses.

PMID- 17439194
TI  - Production of free radicals and triplets from contact radical pairs and from
      photochemically generated radical ions.
AB  - The quantum yields of triplets and free radicals (or radical ions) that escaped
      recombination in photochemically created primary radical pairs (or radical ion
      pairs) are calculated. As the products of monomolecular photodissociation, the
      neutral radicals appear at contact, while the ions are initially distributed over
      the space due to distant photoionization (bimolecular electron transfer) in the
      liquid solution. The diffusional dependence of the quantum yields is shown to be
      different when recombination starts from contact or from separated reactants. The
      experimental data for recombination of ionized perylene with aromatic amine
      counterions is well fitted with the noncontact initial distribution provided the
      recombination is also noncontact and even more distant than ionization.

PMID- 17439195
TI  - Stress dependence of sapphire cathodoluminescence from optically active oxygen
      defects as a function of crystallographic orientation.
AB  - The cathodoluminescence (CL) spectrum of the synthetic sapphire single crystal
      has been studied with respect to the different crystallographic planes of the
      crystal in order to describe the tensorial stress dependence of the band related
      to oxygen defects. Experiments provide the link between CL spectral shift and
      stress, which is referred to as the piezo-spectroscopic (PS) relationship. Using
      the biaxial stress field developed at the tip of cracks generated from the
      corners of a Vickers indentation, we clearly detected stress dependence for the
      cumulative band arising from the F+-center transition of optically active oxygen
      vacancies. The matrix of PS coefficients along different crystallographic axes of
      single-crystal sapphire could be precisely determined. The shallow nature of the
      electron probe may enable the characterization of surface stress fields with a
      spatial resolution that may not be easily available by conventional laser probes.
      The PS calibration results collected on oxygen-defect bands allow the direct
      determination of unknown surface residual stress fields stored in sapphire
      substrates for electronics applications.

PMID- 17439196
TI  - Polarization consistent basis sets. 4: the elements He, Li, Be, B, Ne, Na, Mg,
      Al, and Ar.
AB  - Polarization consistent basis sets, optimized for density functional
      calculations, are proposed for the elements He, Li, Be, B, Ne, Na, Mg, Al, and
      Ar. The basis sets for He, B, Ne, Al, and Ar are assigned based on the previously
      proposed basis sets for H, C-F, and Si-Ar. The basis sets for Li, Be, Na, and Mg
      are defined based on energetic analysis along the lines used in previous work and
      the performance for molecular systems. The performance for atomization energies
      is comparable to those for systems composed of the elements H, C-F, and Si-Ar.

PMID- 17439197
TI  - Density functional theory study on anti-resonance in preresonance Raman
      scattering for naphthalene molecules.
AB  - The anti-resonance phenomenon in preresonance Raman scattering is investigated on
      the basis of the direct Taylor expansion of the electric dipole transition
      moments in vibrational Raman tensors with respect to vibrational normal
      coordinates. A time-dependent density functional theory treatment is applied to
      compute the anti-resonance of a nontotally symmetric vibrational model for
      naphthalene molecules, and the model spectra agree favorably with experiment.
      This direct evaluation approach may provide a method of predicting anti-resonance
      and studying its origin.

PMID- 17439198
TI  - Tight-binding density functional theory: an approximate Kohn-Sham DFT scheme.
AB  - The DFTB method is an approximate KS-DFT scheme with an LCAO representation of
      the KS orbitals, which can be derived within a variational treatment of an
      approximate KS energy functional. But it may also be related to cellular Wigner
      Seitz methods and to the Harris functional. It is an approximate method, but it
      avoids any empirical parametrization by calculating the Hamiltonian and overlap
      matrices out of DFT-derived local orbitals (atomic orbitals, AO's). The method
      includes ab initio concepts in relating the Kohn-Sham orbitals of the atomic
      configuration to a minimal basis of the localized atomic valence orbitals of the
      atoms. Consistent with this approximation, the Hamiltonian matrix elements can
      strictly be restricted to a two-center representation. Taking advantage of the
      compensation of the so-called "double counting terms" and the nuclear repulsion
      energy in the DFT total energy expression, the energy may be approximated as a
      sum of the occupied KS single-particle energies and a repulsive energy, which can
      be obtained from DFT calculations in properly chosen reference systems. This
      relates the method to common standard "tight-binding" (TB) schemes, as they are
      well-known in solid-state physics. This approach defines the density-functional
      tight-binding (DFTB) method in its original (non-self-consistent) version.

PMID- 17439199
TI  - Vibrational levels of methanol calculated by the reaction path version of
      MULTIMODE, using an ab initio, full-dimensional potential.
AB  - An accurate potential energy surface has been determined for methanol from ab
      initio potential data at the CCSD(T) level of theory with an aug-cc-pVTZ basis.
      The resulting potential function is valid over all twelve vibrational degrees of
      freedom for all near-equilibrium and torsional configurations. A torsional
      reaction path has been derived for this potential, from which the low-lying
      vibrational levels of methanol have been calculated by the reaction path version
      of MULTIMODE. Comparisons with experiment and other calculations are made.

PMID- 17439200
TI  - Nature of the aqueous hydroxide ion probed by X-ray absorption spectroscopy.
AB  - X-ray absorption spectra of aqueous 4 and 6 M potassium hydroxide solutions have
      been measured near the oxygen K edge. Upon addition of KOH to water, a new
      spectral feature (532.5 eV) emerges at energies well below the liquid water pre
      edge feature (535 eV) and is attributed to OH- ions. In addition to spectral
      changes explicitly due to absorption by solvated OH- ions, calculated XA spectra
      indicate that first-solvation-shell water molecules exhibit an absorption
      spectrum that is unique from that of bulk liquid water. It is suggested that this
      spectral change results primarily from direct electronic perturbation of the
      unoccupied molecular orbitals of first-shell water molecules and only secondarily
      from geometric distortion of the local hydrogen bond network within the first
      hydration shell. Both the experimental and the calculated XA spectra indicate
      that the nature of the interaction between the OH- ion and the solvating water
      molecules is fundamentally different than the corresponding interactions of
      aqueous halide anions with respect to this direct orbital distortion. Analysis of
      the Mulliken charge populations suggests that the origin of this difference is a
      disparity in the charge asymmetry between the hydrogen atoms of the solvating
      water molecules. The charge asymmetry is induced both by electric field effects
      due to the presence of the anion and by charge transfer from the respective ions.
      The computational results also indicate that the OH- ion exists with a
      predominately "hyper-coordinated" solvation shell and that the OH- ion does not
      readily donate hydrogen bonds to the surrounding water molecules.

PMID- 17439202
TI  - Synthesis and in vitro antiprotozoal activities of dicationic 3,5
      diphenylisoxazoles.
AB  - 3,5-bis(4-amidinophenyl)isoxazole (3)-an analogue of 2,5-bis(4
      amidinophenyl)furan (furamidine) in which the central furan ring is replaced by
      isoxazole-and 42 novel analogues were prepared by two general synthetic pathways.
      The 43 isoxazole derivatives were assayed against Trypanosoma brucei rhodesiense
      (T. brucei rhodesiense) STIB900, Plasmodium falciparum (P. falciparum) K1, and
      rat myoblast L6 cells (for cytotoxicity) in vitro. Eleven compounds (3, 13, 16
      18, 22, 26, 29, 31, 37, and 41) exhibited antitrypanosomal IC50 values less than
      10 nM, five of which displayed cytotoxic indices (ratios of cytotoxic IC50 to
      antiprotozoal IC50 values) at least 10 times higher than that of furamidine.
      Eighteen compounds (4-8, 12, 14, 18-22, 25, 26, 28, 29, 32, and 43) were more
      active against P. falciparum than furamidine, with IC50 values less than 15 nM.
      Fourteen of these compounds had cytotoxic indices ranging between 10 and 120
      times higher than that of furamidine, and five analogues exhibited high
      selectivity for P. falciparum over T. brucei rhodesiense.

PMID- 17439203
TI  - Cluj and related polynomials applied in correlating studies.
AB  - A counting polynomial P(G,x) is a description of a graph property P(G) in terms
      of a sequence of numbers so that the exponents express the extent of its
      partitions while the coefficients are related to the frequency of the occurrence
      of partitions. Basic definitions and properties of Cluj counting polynomials
      CJ(G,x) and their relation with Omega(G,x) and NOmega(G,x) polynomials are
      presented. Analytical relations for the calculation of such polynomials and their
      single-number descriptors in some classes of planar polyhexes are derived. The
      ability of these descriptors to predict the boiling point, chromatographic
      retention index, and resonance energy for some planar polyhex compounds, as well
      as the toxicity of a set of dibenzofurans, is demonstrated.

PMID- 17439204
TI  - Cyclometallated iridium and platinum complexes with noninnocent ligands.
AB  - The electronic properties of the cyclometalated (CwedgeN) complexes of iridium
      and platinum metals with a catechol ligand have been studied experimentally and
      computationally. The synthesis and characterization of (p-tolylpyridine)Ir(3,5-di
      tert-butylcatechol) (abbreviated Ir-sq) and (2,4-diflorophenylpyridine)Pt(3,5-di
      tert-butylcatechol) (abbreviated Pt-sq) are reported along with their structural,
      spectral, and electrochemical properties. Reaction of the 3,5-di-tert
      butylcatechol (DTBCat) ligand with the prepared cyclometalated metal complex was
      carried out in air in the presence of a base. The resulting complexes are air
      stable and are paramagnetic with the unpaired electron residing mainly on the
      catechol ligand. The bond lengths obtained from X-ray structure analysis and the
      theoretical results suggest the semiquinone form of the catechol ligand. Low
      energy, intense (approximately 10(3) M-1 cm-1) transitions are observed in the
      visible to near-infrared region (600-700 nm) of the absorption spectra of the
      metal complexes. Electrochemically, the complexes exhibit a reversible reduction
      of the semiquinone form to the catechol form of the ligand and an irreversible
      oxidation to the unstable quinone form of the ligand. The noninnocent catechol
      ligand plays a significant role in the electronic properties of the metal
      complexes. Density functional theory (DFT) and time-dependent density functional
      theory (TD-DFT) calculations on the two open-shell molecules provide the ground
      state and excited-state energies of the molecular orbitals involved in the
      observed low-energy transitions. The spin density in the two complexes resides
      mainly on the catechol ligand. The intense transition arises from excitation of
      the beta electron from a HOMO-n (n = 1 or 2 here) to the LUMO, rather than from
      the excitation of the unpaired alpha electron.

PMID- 17439205
TI  - Exploring lanthanide luminescence in metal-organic frameworks: synthesis,
      structure, and guest-sensitized luminescence of a mixed europium/terbium-adipate
      framework and a terbium-adipate framework.
AB  - Two lanthanide-organic frameworks were synthesized via hydrothermal methods.
      Compound 1 ([(Eu,Tb)(C6H8O4)3(H2O)2].(C10H8N2), orthorhombic, Pbcn, a = 21.925(2)
      A, b = 7.6493(7) A, c = 19.6691(15) A, alpha = beta = gamma = 90 degrees, Z = 4)
      takes advantage of the similar ionic radii of the lanthanide elements to induce a
      mixed-lanthanide composition. Compound 2 ([Tb2(C6H8O4)3(H2O)2].(C10H8N2),
      orthorhombic, Pbcn, a = 21.866(3) A, b = 7.6101(10) A, c = 19.646(3) A, alpha =
      beta = gamma = 90 degrees, Z = 8) is the terbium-only analogue of compound 1.
      Solid-state measurements of their luminescence behavior demonstrate that the
      neutral guest molecule (4,4'-dipyridyl) residing in the extraframework channels
      is successful in sensitizing lanthanide ion emission. In compound 1,
      columinescence occurs, and both lanthanide ions show emission. Additionally,
      quantum yield and lifetime measurements support the premise that the Tb3+ center
      is also acting to sensitize the Eu3+, effectively enhancing Eu3+ emission.

PMID- 17439206
TI  - Au3SnP7@black phosphorus: an easy access to black phosphorus.
AB  - Black phosphorus can be prepared under low-pressure conditions at 873 K from red
      phosphorus via the addition of small quantities of gold, tin, and tin(IV) iodide.
      Au3SnP7, AuSn, and Sn4P3 were observed as additional phases. Tin(IV) iodide
      remains unreacted during the preparation process. The crystal structure of black
      phosphorus was redetermined from single crystals. P (295 K): a = 3.316(1) A, b =
      10.484(2) A, c = 4.379(1) A, V = 152.24(6) A3, space group Cmce (No. 64). Solid
      state 31P MAS NMR spectroscopy and X-ray powder diffraction were performed to
      substantiate the high crystal quality of black phosphorus. A possible mechanism
      for the formation is discussed in terms of the comparable structural features of
      black phosphorus and Au3SnP7. Thermodynamic calculations showed that the only
      relevant gas-phase species, P4, and the transport reactions are not suitable for
      the preparation of orthorhombic black phosphorus at temperatures above 773 K. A
      kinetically controlled mechanism must be favored instead of a thermodynamically
      controlled formation. The new preparation method of black phosphorus represents
      an easy and effective way to avoid complicated preparative setups, toxic
      catalysts, or "dirty" flux methods and is of general interest in elemental
      chemistry.

PMID- 17439207
TI  - Preparation and coordination complex of the first imine-bridged
      tetrathiafulvalene-pyridine donor ligand.
AB  - The first imine-bridged pyridyltetrathiafulvalene building block (TTF-CH=N-Py, 1)
      has been synthesized via the Schiff base condensation of formyltetrathiafulvalene
      and 2-aminopyridine. The preparation, X-ray crystal structure, electrochemical
      and magnetic characterization of a 1:1 copper complex [CuII(hfac)2(TTF-CH=N-Py)]
      (2) are reported. The crystal structure reveals that the imine N atom
      participates in chelation to the paramagnetic center, thus making this ligand an
      attractive precursor for the assembly of pi-d systems.

PMID- 17439208
TI  - Structural study of amorphous tellurium(II) halides TeCl2-xIx (x = 0.5, 0.1): X
      ray diffraction and reverse Monte Carlo simulations.
AB  - The addition of small amounts of iodine to thermodynamically instable TeCl2
      yields amorphous, glassy tellurium(II) halides TeCl2-xIx (0.1 < x < 0.5), which
      were prepared by rapid quenching of melts with the respective compositions. At
      ambient temperature, these glassy solids are sufficiently stable to be handled
      and investigated by analytical methods. High-energy X-ray diffraction and reverse
      Monte Carlo simulations of two compositions TeCl2-xIx, x = 0.1 and 0.5, show that
      these glasses are made up of structural fragments that are present in both
      tellurium tetrahalides and in low-valent tellurium subhalides. In both glasses,
      the Te-Te bonding shows narrow coordination distribution with a mean total
      coordination number for the Te atoms of 4.1 +/- 1.3 and a mean Te-Te coordination
      number of 0.7 +/- 0.7. Accordingly, the mean Cl-Te coordination number is 1.7 +/-
      0.8 and the mean I-Te coordination number is 1.6 +/- 0.7. The medium-range order
      increases with increasing iodine content.

PMID- 17439209
TI  - Tuning the selectivity/specificity of fluorescent metal ion sensors based on N2S2
      pyridine-containing macrocyclic ligands by changing the fluorogenic subunit:
      spectrofluorimetric and metal ion binding studies.
AB  - Two new fluorescent chemosensors for metal ions have been synthesized and
      characterized, and their photophysical properties have been explored; they are
      the macrocycles 5-(2-quinolinylmethyl)-2,8-dithia-5-aza-2,6-pyridinophane (L5)
      and 5-(5-chloro-8-hydroxyquinolinylmethyl)-2,8-dithia-5-aza-2,6-pyridinophane
      (L6). Both systems have a pyridyl-thioether-containing 12-membered macrocycle as
      a binding site. The coordination properties of these two ligands toward CuII,
      ZnII, CdII, HgII, and PbII have been studied in MeCN/H2O (1:1 v/v) and MeCN
      solutions and in the solid state. The stoichiometry of the species formed at 25
      degrees C have been determined from absorption, fluorescence, and potentiometric
      titrations. The complexes [CuL5](ClO4)(2).1/2MeCN, [ZnL5(H2O)](ClO4)2,
      [HgL5(MeCN)](ClO4)2, [PbL5(ClO4)2], [Cu3(5-Cl-8-HDQH-1)(L6H-1)2](ClO4)(3).7.5H2O
      (HDQ=hydroxyquinoline), and [Cu(L6)2](BF4)(2).2MeNO2 have also been characterized
      by X-ray crystallography. A specific CHEF-type response of L5 and L6 to the
      presence of ZnII and CdII, respectively, has been observed at about pH 7.0 in
      MeCN/H2O (1:1 v/v) solutions.

PMID- 17439210
TI  - Rich pseudopolymorphic behavior of the tetranuclear [Ni4(dpyatriz)2(NO3)8]
      complex.
AB  - Reaction of nickel(II) nitrate with the dpyatriz ligand, namely 2,4,6
      tris(bis(pyridin-2-yl)amino)-1,3,5-triazine, in acetonitrile produces a
      tetranuclear NiII coordination compound,
      [Ni4(dpyatriz)2(NO3)8(CH3CN)2(H2O)2].2CH3CN (1), the crystal structure of which
      has been determined by X-ray diffraction using a synchrotron source. 1 has been
      characterized by IR and UV-vis spectroscopy, elemental and thermogravimetric
      analyses, and magnetic susceptibility measurements. Its solid-state structure
      exhibits remarkable anion...pi interactions between coordinated nitrate ions and
      the triazine rings. In addition, a thorough X-ray powder diffraction study has
      revealed a number of pseudopolymorphic phases (2-5), resulting from various
      degrees of hydration/solvation of the [Ni4(dpyatriz)2] core. The interconversion
      scheme among the different phases has been determined using controlled heating,
      and the basic structural features of the different pseudopolymorphs have been
      assessed through ab initio powder diffraction methods.

PMID- 17439211
TI  - Pd catalysis on dendronized solid support: generation effects and the influence
      of the backbone structure.
AB  - Recent studies revealed that catalysts, prepared on dendronized support,
      frequently exhibit enhanced activity and selectivity as compared to their non
      dendronized analogues. Regretfully, in early studies of the supported dendritic
      catalysis, no particular attention was paid to the coordinative nature of the
      dendritic backbone. In this study, we functionalized Wang polystyrene support
      with three types of dendritic templates: poly(aril benzyl ether), poly(aryl
      benzyl thioether), and poly(aryl benzyl amine). These dendronized resins were
      further decorated with phosphine ligands on the periphery and complexed with a
      Pd(0) catalytic precursor. The catalysis of the Heck and Suzuki reactions of
      bromobenzene with the first to third generation supported dendritic catalysts was
      examined and compared to that of the non-dendritic analogues. All of the examined
      reactions revealed a positive dendritic effect, reflected in up to 5-fold
      increase in yield, in the most prominent case. The reasons for the observed
      effect are the proximity of the ligating sites translated into reduced cross
      linking and, probably, the increased distance of the catalyst from the polymer
      matrix. We proved, however, that the latter could not be achieved with a linear
      spacer. Although the Suzuki reaction was rather insensitive to the backbone
      structure, the Heck reaction catalysis at 80 degrees C exhibited substantial
      sensitivity to the nature of the dendritic backbone, with the polyether structure
      demonstrating the best outcome. This is the first demonstration of the influence
      of the coordinative ability of the backbone on the activity of a supported
      dendritic catalyst.

PMID- 17439212
TI  - Artificial G-wire switch with 2,2'-bipyridine units responsive to divalent metal
      ions.
AB  - Development of a guanine nanowire (G-wire) that is controllable and can be
      switched by external signals is important for the creation of molecular
      electronic technologies. Here, we constructed a G-wire in which the thymines of
      the main chain of d(G4T4G4) were replaced with 2,2'-bipyridine units, which have
      two aromatic rings that rotate arbitrarily upon coordination with metal ions.
      Circular dichroism of the DNA oligonucleotides with or without the 2,2'
      bipyridine unit showed that divalent metal ions induce the bipyridine-containing
      oligonucleotide to switch from an antiparallel to a parallel G-quadruplex. Native
      polyacrylamide gel electrophoresis showed that the parallel-stranded G-quadruplex
      DNA had a high-order structure. Circular dichroism and native gel electrophoresis
      analyses suggested that adding Na2EDTA causes a reverse structural transition
      from a parallel-stranded high-order structure to an antiparallel G-quadruplex.
      Moreover, atomic force microscopy showed a long nanowire ( approximately 200 nm)
      in the presence of Ni2+ but no significant image in the absence of Ni2+ or in the
      presence of both Ni2+ and Na2EDTA. These observations revealed that the parallel
      stranded high-order structure is a G-wire containing numerous DNA oligonucleotide
      strands bound together via divalent metal ion-2,2'-bipyridine complexes. Finally,
      we found that alternating addition of Ni2+ and Na2EDTA can cycle the G-wire
      between the high-order and disorganized structures, with an average cycling
      efficiency of 0.95 (i.e., 5% loss per cycle). These results demonstrate that a
      DNA oligonucleotide incorporating the 2,2'-bipyridine unit acts as a G-wire
      switch that can be controlled by chemical input signals, namely, divalent metal
      ions.

PMID- 17439213
TI  - Study of the coalescence of acoustic bubbles as a function of frequency, power,
      and water-soluble additives.
AB  - The effect that surface-active solutes, such as aliphatic alcohols and sodium
      dodecyl sulfate (SDS), have on the extent of bubble coalescence in liquids under
      different sonication conditions has been investigated by measuring the volume
      change of the solution following a period of sonication. In general, the
      adsorption of surface-active solutes onto the bubble surface retards bubble
      coalescence. Within the limitations of the measurement method and the systems
      studied, bubble coalescence does not appear to be dependent on the applied
      acoustic power. Also, varying the applied acoustic frequency has a minimal effect
      on the extent of bubble coalescence in systems where long-range electrostatic
      repulsion between bubbles, imparted by the adsorbed surface-active solutes,
      dominates. However, when short-range steric repulsion (or other short-range
      repulsive forces) is the primary factor in inhibiting bubble coalescence, the
      dependence on the applied acoustic frequency becomes apparent, with less
      coalescence inhibition at higher frequencies. It is also concluded that SDS does
      not reach an equilibrium adsorption level at the bubble/solution interface under
      the sonication conditions used. On the basis of this conclusion, a method is
      proposed for estimating nonequilibrium surface excess values for solutes that do
      not fully equilibrate with the bubble/solution interface during sonication. For
      the case of SDS in the presence of excess NaCl, the method was further employed
      to estimate the maximum lifetime of bubbles in a multibubble field. It was
      concluded that an acoustic bubble in a multibubble field has a finite lifetime,
      and that this lifetime decreases with increasing applied frequency, ranging from
      up to 0.35 +/- 0.05 ms for 213 kHz to 0.10 +/- 0.05 ms for 1062 kHz. These
      estimated lifetimes equate to a bubble in a multibubble field undergoing an upper
      limit of 50-200 oscillations over its lifetime for applied ultrasound frequencies
      between 200 kHz and 1 MHz.

PMID- 17439214
TI  - Oxoclusters of the lanthanides begin to resemble solid-state materials at very
      small cluster sizes: structure and NIR emission from Nd(III).
AB  - The reaction of Nd(SePh)3 with SeO2 and Hg in pyridine gives the dodecanuclear
      cluster [(py)18Nd12O6Se4(Se2)4(SePh)4(Se2Ph)2Hg2(SePh)4][(Hg(SePh)3]2. In this
      compound the 12 Nd(III) ions are stacked in four sets of Nd3, with pairs of
      tetrahedral oxo ligands separating the Nd3 planes and Se, SeSe, SePh, pyridine,
      and HgSePh groups encapsulating the oxo core. Both the Nd-O bond lengths and the
      geometries about the oxo ions are remarkably similar to those found in solid
      state Nd2O3. Near-IR emission experiments indicate that the cluster emission
      properties are less intense than those of highly emissive (DME)2Nd(SC6F5)3 or
      (THF)8Nd8O2Se2(SePh)16 but brighter than the nonemissive solid-state compound
      Nd2O3. Intensity variations are interpreted in terms of concentration quenching
      and phonon relaxation.

PMID- 17439215
TI  - Biodegradable nanogels prepared by atom transfer radical polymerization as
      potential drug delivery carriers: synthesis, biodegradation, in vitro release,
      and bioconjugation.
AB  - Stable biodegradable nanogels cross-linked with disulfide linkages were prepared
      by inverse miniemulsion atom transfer radical polymerization (ATRP). These
      nanogels could be used for targeted drug delivery scaffolds for biomedical
      applications. The nanogels had a uniformly cross-linked network, which can
      improve control over the release of encapsulated agents, and the nanogels
      biodegraded into water-soluble polymers in the presence of a biocompatible
      glutathione tripeptide, which is commonly found in cells. The biodegradation of
      nanogels can trigger the release of encapsulated molecules including rhodamine
      6G, a fluorescent dye, and Doxorubicin (Dox), an anticancer drug, as well as
      facilitate the removal of empty vehicles. Results obtained from optical
      fluorescence microscope images and live/dead cytotoxicity assays of HeLa cancer
      cells suggested that the released Dox molecules penetrated cell membranes and
      therefore could suppress the growth of cancer cells. Further, OH-functionalized
      nanogels were prepared to demonstrate facile applicability toward bioconjugation
      with biotin. The number of biotin molecules in each nanogel was determined to be
      142,000, and the formation of bioconjugates of nanogels with avidin was confirmed
      using optical fluorescence microscopy.

PMID- 17439216
TI  - Highly Efficient Au(I)-catalyzed intramolecular addition of beta-ketoamide to
      unactivated alkenes.

PMID- 17439217
TI  - Two-faced reactivity of alkenes: cis- versus trans-aminopalladation in aerobic Pd
      catalyzed intramolecular aza-Wacker reactions.
AB  - A number of different PdII catalyst systems have been reported recently for the
      Wacker-type aerobic oxidative cyclization of alkenes bearing tethered nitrogen
      nucleophiles. This study examines the stereochemistry of the aminopalladation
      step with five different catalyst systems: Pd(OAc)2/DMSO (A), PdX2/pyridine [X =
      OAc (B), O2CCF3 (C)], Pd(IMes)(O2CCF3)2(OH2) (D), and Pd(O2CCF3)2/(-)-sparteine
      (E). Use of a stereospecifically deuterated cyclopentene substrate reveals that
      four of the five catalyst systems (A, B, C, and E) promote exclusive cis
      aminopalladation of the alkene, whereas both cis- and trans-aminopalladation
      occur with the N-heterocyclic-carbene (NHC) catalyst system. If stoichiometric
      Bronsted base (NaOAc, Na2CO3) is added to the latter reaction conditions,
      however, only cis-aminopalladation is observed. The identity of the nitrogen
      nucleophile also affects the aminopalladation pathway, with results ranging from
      exclusively cis- to exclusively trans-aminopalladation. These results have
      important implications for ongoing efforts to develop enantioselective methods
      for Pd-catalyzed oxidative amination of alkenes.

PMID- 17439218
TI  - Cyclodimerization of alkynes with phosphine-free ruthenium carbene complexes:
      carbene consumption by a shunted alkyne oligomerization.

PMID- 17439219
TI  - Unsaturated platinum-rhenium cluster complexes. Synthesis, structures and
      reactivity.
AB  - Two new compounds PtRe3(CO)12(PBut3)(micro-H)3, 9, and PtRe2(CO)9(PBut3)(micro
      H)2, 10, were obtained from the reaction of Pt(PBut3)2 with Re3(CO)12(micro-H3),
      8, at room temperature. Compound 9 contains a butterfly cluster of four metals
      formed by the insertion of the platinum atom from a Pt(PBut3) group into one of
      the hydride-bridged metal-metal bonds of 8. The three hydrido ligands are
      bridging ligands across each of three new Pt-Re bonds. Compound 10 contains a
      triangular PtRe2 cluster with two hydrido ligands; one bridges a Pt-Re bond, and
      the other bridges the Re-Re bond. The new compound Pt2Re2(CO)7(PBut3)2(micro-H)2,
      11, was obtained from the reaction of 8 with Pt(PBut3)2 in hexane at reflux.
      Compound 11 was also obtained from 10 by reaction with an additional quantity of
      Pt(PBut3)2. Compound 11 contains a tetrahedral cluster of four metal atoms with
      two dynamically active hydrido ligands. A CO ligand on one of the two platinum
      atoms also exchanges between the two platinum atoms rapidly on the NMR time
      scale. Compound 11 is electronically unsaturated and was found to add hydrogen at
      room temperature to form the tetrahydrido cluster complex,
      Pt2Re2(CO)7(PBut3)2(micro-H)4, 12. Compound 12 has a structure similar to 11 but
      contains one triply bridging hydrido ligand, two edge bridging hydrido ligands,
      and one terminal hydrido ligand on one of the two platinum atoms. A kinetic
      isotope effect D/H of 1.5(1) was determined for the addition of H2 to 11.
      Hydrogen can be eliminated from 12 by heating to 97 degrees C or by the
      application of UV-vis irradiation at room temperature. Compound 12 adds CO at
      room temperature to yield the complex Pt2Re2(CO)8(PBut3)2(micro-H)4, 13, which
      contains a planar cluster of four metal atoms with a Pt-Pt bond and four edge
      bridging hydrido ligands. Compounds 11 and 12 react with Pt(PBut3)2 to yield the
      known five metal cluster complexes Pt3Re2(CO)6(PBut3)3(micro-H)2, 14, and
      Pt3Re2(CO)6(PBut3)3(micro-H)4, 15, respectively. Density functional calculations
      confirm the hydride positions in the lowest energy structural isomers of 11 and
      12 and suggest a mechanism for H2 addition to 11 that occurs on the Pt atom with
      the lower coordination number.

PMID- 17439220
TI  - Nigricanosides A and B, antimitotic glycolipids isolated from the green alga
      Avrainvillea nigricans collected in Dominica.

PMID- 17439221
TI  - A concise synthesis of butylcycloheptylprodigiosin.
AB  - A short and efficient total synthesis of the tripyrrole alkaloid
      butylcycloheptylprodigiosin is described. Key to the brevity of the approach is a
      two-step synthesis of macrocyclic formylpyrrole 4 from cyclononenone 6.

PMID- 17439222
TI  - Alkyne as a spectator ligand for the nickel-catalyzed multicomponent connection
      reaction of diphenylzinc, 1,3-butadiene, aldehydes, and amines.
AB  - Under nickel catalysis, in the presence of 3-hexyne, the aldimines of aromatic
      amines react with Ph2Zn and one molecule of butadiene to provide 1 exclusively,
      while the aldimines of aliphatic amines react with Ph2Zn and two molecules of
      butadiene to provide 2 exclusively, where 3-hexyne serves as a spectator ligand
      controlling the selective formation of 1 and 2.

PMID- 17439223
TI  - Total synthesis of eustifolines A-D and glycomaurrol via a divergent Diels-Alder
      strategy.
AB  - The Diels-Alder reaction between a quinone monoimine and cyclic diene allows for
      the construction of substituted carbazoles in a regiospecific manner. This
      methodology has sucessfully been employed in a divergent strategy, culminating in
      the synthesis of eustifolines A-D and glycomaurrol.

PMID- 17439224
TI  - Chiral molecular clips control orthogonal crystalline organization.
AB  - Chiral molecular clips constitute a robust system for crystal engineering studies
      and undergo several levels of orthogonal organization including heterochiral
      dimerization, H-bond or metal-ligand mediated tape formation, and longitudinal
      packing of the tapes.

PMID- 17439226
TI  - Computational study of the stereochemistry of intramolecular carbolithiation of
      an alkene by a secondary alkyllithium: stereochemistry change caused by a single
      THF molecule of solvation.
AB  - Theoretical calculations reveal that the 40:1 ratio of trans- to cis-2
      methylcyclopentylmethyllithium formed in the cyclization of 6-lithio-1-heptene by
      intramolecular carbolithiation is due to steric crowding in the transition state
      for the cis-cyclization pathway when a single THF molecule complexes the lithium
      cation. In the absence of this specific solvation, the cis-cyclization pathway is
      predicted to be slightly favored.

PMID- 17439225
TI  - Synthesis of L-kedarosamine in protected form and its efficient incorporation
      into an advanced intermediate to kedarcidin chromophore.
AB  - An efficient route to the complex L-kedarosamine alpha-glycosidic ether 2, a
      synthetic precursor to kedarcidin chromophore, is described. Central to the
      route, which is suitable for the preparation of multigram amounts of material, is
      a short synthetic sequence from D-threonine to protected L-kedarosamine
      derivatives and methodology for their alpha-selective coupling with appropriate
      hydroxyl acceptors.

PMID- 17439227
TI  - Benzimidazole-based tripodal receptor: highly selective fluorescent chemosensor
      for iodide in aqueous solution.
AB  - We synthesized a novel tripodal fluorescent receptor bearing benzimidazole motifs
      as recognition sites in the pods of the receptor. The recognition behavior of the
      receptor toward various anions was evaluated in CH3CN/H2O (9:1, v/v) solution.
      The receptor showed changes in fluorescent intensity only with I-, but it showed
      no significant changes on addition of other anions such as F-, Cl-, Br-, HSO4-,
      NO3-, CH3COO-, and H2PO4-.

PMID- 17439228
TI  - Dinuclear zinc-catalyzed enantioselective Aza-Henry reaction.
AB  - The dinuclear zinc catalyst 1a was found to catalyze the addition of nitroalkanes
      to carbamate-protected imines. This aza-Henry reaction proceeds with high
      enantioselectivity when various carbamate-protected imines are used. alpha,beta
      Unsaturated imines proved to be a particularly useful class of substrate
      routinely giving the alpha-nitro amine products in high enantiomeric excess.

PMID- 17439229
TI  - Late watergrass (Echinochloa phyllopogon): mechanisms involved in the resistance
      to fenoxaprop-p-ethyl.
AB  - Fenoxaprop-p-ethyl (FE), 2-[4-[(6-chloro-2-benzoxazolyl)oxy]phenoxy] propanoate,
      ethyl ester (R), is an aryloxyphenoxypropionate herbicide for postemergence
      control of annual and perennial grasses in paddy fields; its site of action is
      acetyl-coenzyme A carboxylase (ACCase), an enzyme in fatty acids biosynthesis.
      The possible mechanism(s) of resistance to FE in a resistant biotype of
      Echinochloa phyllopogon was examined, namely, absorption, translocation, and
      metabolism of FE and ACCase susceptibility to fenoxaprop acid (FA). Studies of
      the in vitro inhibition of ACCase discounted any differential active site
      sensitivity as the basis of resistance to FE. There were differences in
      absorption rates between biotypes from 3 to 48 h after application (HAA).
      Biotypes did not differ in either the amounts or the rates of FE translocated;
      98% of applied [14C]FE remaining in the treated leaf. However, there was a good
      correlation between the rate of herbicide metabolism and the plant resistance.
      The R biotype produced 5-fold less FA and approximately 2-fold more nontoxic
      (polar) metabolites 48 HAA than the S biotype. Moreover, the higher rate of GSH
      conjugation in the resistant biotype as compared to the susceptible one indicates
      that GSH and cysteine conjugation is the major mechanism of resistance of the R
      biotype against FE toxicity.

PMID- 17439230
TI  - Biotransformation of common bean (Phaseolus vulgaris L.) flavonoid glycosides by
      bifidobacterium species from human intestinal origin.
AB  - Bifidobacteria strains from human origin were screened for the specific activity
      (beta-glucosidase activity) involved in the metabolism of dietary flavonoids.
      Five strains with high beta-glucosidase activity were selected for further
      metabolism analyses (high-performance liquid chromatography separations) of
      flavonoid glycosides occurring in Phaseolus vulgaris L. (common bean) seeds and
      seedlings. All selected strains were found to be active in the conversion of
      kaempferol 3-O-glucoside, daidzin, genistin, and glycitin into their aglyconic
      forms. No metabolites were detected after the fermentation tests with the
      diglucosidic compound kaempferol 3-O-xylosylglucoside. In addition, to verify the
      effective bioavailability of flavonoid aglycones, the degradation rates of
      daidzein, genistein, glycitein, and kaempferol, following incubation with
      selected strains, were monitored. The results showed that the five selected
      strains of bifidobacteria, being active in the biotranformation of flavonoid
      glycosides occurring in common bean seeds and seedlings, could be considered as
      probiotic dietary adjuncts to improve the nutritional and health properties of
      flavonoid-based products, comprising hypothetical common bean food derivatives.

PMID- 17439231
TI  - Structural constituents of the seagrass Posidonia australis.
AB  - Large amounts of seagrass, Posidonia australis, wash onto beaches in South
      Australia each year, causing substantial environmental problems. It was of
      interest to assess the potential for an economic use of this seagrass-such as for
      animal nutrition. Structural constituents of P. australis (green, freshly
      deposited, and both washed and unwashed samples from dried deposits on the beach)
      were examined and compared. Glucose, galactose, and mannose were the dominant
      sugars (>10 g kg-1 of dry matter) in the soluble fraction of nonstarch
      polysaccharides in all seagrass forms. The content of the insoluble constituents
      of the nonstarch polysaccharides was significantly higher than soluble nonstarch
      polysaccharide constituents (P < 0.01). Data showed that the major constituents
      of the Posidonia cell wall are cellulose and lignin (190-209 and 145-154 g kg-1,
      respectively). The crude protein content of Posidonia ranged from 54 to 61 g kg
      1. Results showed no biologically significant compositional differences between
      the four different forms of seagrass tested. Dry, unwashed seagrass, which is
      readily available in large quantities and easily harvested, may have potential as
      a foodstuff for ruminant animals.

PMID- 17439232
TI  - Structural motifs of syringyl peroxidases are conserved during angiosperm
      evolution.
AB  - The most distinctive variation in the monomer composition of lignins in vascular
      land plants is that between the two main groups of seed plants. Thus, whereas
      gymnosperm (softwood) lignins are typically composed of guaiacyl (G) units,
      angiosperm (hardwood) lignins are largely composed of similar levels of G and
      syringyl (S) units. However, there are some studies that suggest that certain
      angiosperm peroxidases are unable to oxidize sinapyl alcohol, and a coniferyl
      alcohol shuttle has been proposed for oxidizing S units during the biosynthesis
      of lignins. With this in mind, a screening of the presence of S peroxidases in
      angiosperms (including woody species and forages) was performed. Contrarily to
      what might be expected, the intercellular washing fluids from lignifying tissues
      of 25 woody, herbaceous, and shrub species, belonging to both monocots and
      dicotyledons, all showed both S peroxidase activities and basic peroxidase
      isoenzymes analogous, with regard the isoelectric point, to the Zinnia elegans
      basic peroxidase isoenzyme, the only S peroxidase that has been fully
      characterized. These results led to the protein database in the search for
      homologies between angiosperm peroxidases and a true eudicot S peroxidase, the Z.
      elegans peroxidase. The findings showed that certain structural motifs of S
      peroxidases are conserved within the first 15 million years of angiosperm
      history, because they are found in peroxidases from the two major lineages of
      flowering plants, eumagnoliids and eudicotyledons, of note being the presence of
      these peroxidases in Amborella and Nymphaeales, which represent the first stages
      of angiosperm evolution. These phylogenetic studies also suggest that guaiacyl
      peroxidases apparently constitute the most "evolved state" of the plant
      peroxidase family evolution.

PMID- 17439233
TI  - Polyunsaturated fatty acids (PUFAs) content of the fungus Mortierella alpina
      isolated from soil.
AB  - Twenty-five isolates of Mortierella spcies were prepared, which can be used for
      the production of polyunsaturated fatty acids (PUFAs)-rich oil for nutritional
      supplements. The fatty acid contents were determined after heterotrophic
      fermentation. The content of total fatty acids (TFAs) in the cell dry weight of
      all isolates including two commercially purchased Mortierella alpina strains
      ranged from 207.51 to 370.11 mg/g, whereas PUFAs were the dominant fatty acid
      type. The highest PUFA-containing strain, M. alpina SC9, was identified and
      confirmed as a new strain of M. alpina through comparison analysis of the
      sequences of internal transcribed spacers 1 and 2 (ITS1 and ITS2) and the 5.8S
      rDNA region. During a 7-day fermentation, the PUFAs content of M. alpina SC9
      varied between 189.83 and 240.00 mg/g, with a remarkable correlation between the
      oleic acid (C18:1, OA) and arachidonic acid (C20:4n-6, AA) contents and between
      the linoleic acid (C18:2n-6, LA) and AA contents, suggesting the PUFA content in
      the fungus is tightly regulated. This study provides a framework of isolation,
      identification, and characterization of an important PUFA-producing species, M.
      alpina.

PMID- 17439234
TI  - Quantitative studies on the formation of phenol/2-furfurylthiol conjugates in
      coffee beverages toward the understanding of the molecular mechanisms of coffee
      aroma staling.
AB  - To gain a more comprehensive knowledge of the contribution of recently identified
      phenol/thiol conjugates to the storage-induced degradation of odorous thiols, the
      concentrations of the sulfury-roasty smelling key odorant 2-furfurylthiol and the
      concentrations of the putative thiol-receptive di- and trihydroxybenzenes
      pyrogallol (1), hydroxyhydroquinone (2), catechol (3), 4-ethylcatechol (4), 4
      methylcatechol (5), and 3-methylcatechol (6), as well as of the phenol/thiol
      conjugates 3-[(2-furylmethyl)sulfanyl]catechol (7), 3-[(2-furylmethyl)sulfanyl]-5
      ethylcatechol (8), 4-[(2-furylmethyl)sulfanyl]hydroxyhydroquinone (9), and 3,4
      bis[(2-furylmethyl)sulfanyl]hydroxyhydroquinone (10) were quantitatively
      determined in fresh and stored coffee beverages by means of stable isotope
      dilution analyses (SIDA). Although 2 was found to be the quantitatively
      predominant trihydroxybenzene in freshly prepared coffee brew, this compound
      exhibited a very high reactivity and decreased rapidly during coffee storage to
      generate the conjugates 9 and 10. After only 10 min, about 60% of the initial
      amount of 2-furfurylthiol in a coffee beverage reacted with 2 to give 9 and 10.
      In contrast, conjugate 7 was found to be exclusively formed during coffee
      roasting because its initial concentration as well as the amount of its putative
      precursor, phenol 3, was not affected by storage. It is interesting to note that
      the concentration of 8 was increased with increasing incubation time, but its
      putative precursor 4 was not affected, thus indicating another formation pathway
      most likely via the chlorogenic acid degradation product 4-vinylcatechol. This
      study demonstrates for the first time that the loss of 2-furfurylthiol during
      coffee storage is mainly due to the oxidative coupling of the odorant to
      hydroxyhydroquinone (2), giving rise to the conjugates 9 and 10.

PMID- 17439236
TI  - Synthesis and characterization of a molecularly imprinted silica gel sorbent for
      the on-line determination of trace Sudan I in Chilli powder through high
      performance liquid chromatography.
AB  - A highly selective imprinted polymer was synthesized by a surface molecular
      imprinting technique in combination with a sol-gel process. The imprinted polymer
      was evaluated by FT-IR and static and kinetic adsorption experiments. The results
      showed that the imprinted sorbent exhibited good recognition and selective
      ability, offered a faster kinetics for the adsorption and desorption of Sudan I
      than the non-imprinted sorbent, a saturated binding capacity (Qmax) that reached
      33.47 mg g-1. The prepared sorbent was applied for the determination of trace
      Sudan I through on-line solid-phase coupled with high-performance liquid
      chromatography (SPE-HPLC). With a loading flow rate of 1.5 mL min-1 for sampling
      50 mL, an enrichment factor of 1266 was achieved. The detection limit (S/N = 3)
      was 1.2 ng L-1, and the peak area precision (RSD) for five replicate detections
      of 0.01 microg L-1 Sudan I was 3.66%. The Sudan I in the chilli powder from the
      local market was determined at three levels (0.25, 0.5, and 1.0 ng g-1) with
      recoveries ranging from 80.31 to 94.02%.

PMID- 17439235
TI  - A new process to develop a cocoa powder with higher flavonoid monomer content and
      enhanced bioavailability in healthy humans.
AB  - Cocoa is a food rich in polyphenols, mainly the flavonoid procyanidins and flavan
      3-ols. The improvement of the cardiovascular function in humans upon cocoa
      consumption has been specifically linked to the presence of flavan-3-ol derived
      metabolites in plasma, especially epicatechin glucuronide. In this context, a
      flavonoid-enriched cocoa-derived product could potentially exert stronger health
      benefits. The aim of the present study was to obtain a cocoa powder with a higher
      flavonoid content (mainly enriched in monomer compounds) and assess its flavonoid
      bioavailability in humans. For this purpose, an unfermented, nonroasted, and
      blanch-treated cocoa powder (A) was obtained. The powder contained four times
      more procyanidins than a conventional (B) cocoa powder. Powder A contained eight
      times more epicatechin and procyanidin B2 than powder B. Cocoa milk drinks were
      prepared with powder A (MDA) and B (MDB). The bioavailability of flavonoids in
      both drinks was assessed in a crossover intervention with healthy volunteers. The
      content of epicatechin glucuronide, the main metabolite detected in plasma, was
      five-fold higher upon consumption of MDA as compared with MDB. The urinary
      excretion of metabolites, mainly methyl epicatechin sulfate, was higher upon MDA
      consumption as compared with MDB, ranging from two- to 12-fold higher depending
      on the metabolite. These results, together with previous reports regarding the
      cardiovascular benefits linked to the presence of procyanidin metabolites in
      plasma, suggest that further clinical trials to validate the health benefits of a
      flavonoid-enriched cocoa powder are warranted.

PMID- 17439237
TI  - Pineapple juice and its fractions in enzymatic browning inhibition of banana
      [Musa (AAA group) Gros Michel].
AB  - The effectiveness of pineapple juice in enzymatic browning inhibition was
      evaluated on the cut surface of banana slices. After storage of banana slices at
      15 degrees C for 3 days, pineapple juice showed browning inhibition to a similar
      extent as 8 mM ascorbic acid but less than 4 mM sodium metabisulfite.
      Fractionation of pineapple juice by a solid-phase C18 cartridge revealed that the
      directly eluted fraction (DE fraction) inhibited banana polyphenol oxidase (PPO)
      about 100% when compared to the control. The DE fraction also showed more
      inhibitory effect than 8 mM ascorbic acid in enzymatic browning inhibition of
      banana puree during storage at 5 degrees C for 24 h. Further identification of
      the DE fraction by fractionation with ion exchange chromatography and
      confirmation using model systems indicated that malic acid and citric acid play
      an important role in the enzymatic browning inhibition of banana PPO.

PMID- 17439238
TI  - Oil and tocopherol content and composition of pumpkin seed oil in 12 cultivars.
AB  - Twelve pumpkin cultivars (Cucurbita maxima D.), cultivated in Iowa, were studied
      for their seed oil content, fatty acid composition, and tocopherol content. Oil
      content ranged from 10.9 to 30.9%. Total unsaturated fatty acid content ranged
      from 73.1 to 80.5%. The predominant fatty acids present were linoleic, oleic,
      palmitic, and stearic. Significant differences were observed among the cultivars
      for stearic, oleic, linoleic, and gadoleic acid content of oil. Low linolenic
      acid levels were observed (<1%). The tocopherol content of the oils ranged from
      27.1 to 75.1 microg/g of oil for alpha-tocopherol, from 74.9 to 492.8 microg/g
      for gamma-tocopherol, and from 35.3 to 1109.7 microg/g for delta-tocopherol. The
      study showed potential for pumpkin seed oil from all 12 cultivars to have high
      oxidative stability that would be suitable for food and industrial applications,
      as well as high unsaturation and tocopherol content that could potentially
      improve the nutrition of human diets.

PMID- 17439240
TI  - Single-cell peptidomics of drosophila melanogaster neurons identified by Gal4
      driven fluorescence.
AB  - Neuropeptides are widespread signal molecules that display a great chemical and
      functional diversity. Predictions of neuropeptide cleavage from precursor
      proteins are not always correct, and thus, biochemical identification is
      essential. Single-cell analysis is valuable to identify peptides processed from a
      single precursor, but also to determine coexpression of further neuropeptides
      from other precursors. We have developed an approach to isolate single identified
      neurons from the fruit fly Drosophila melanogaster for mass spectrometric
      analysis. By using Gal4 promoter lines to drive green fluorescent protein under
      UAS control, we identified specific peptidergic neurons. These neurons were
      isolated singly under a fluorescence microscope and subjected to MALDI-TOF mass
      spectrometry. Two Gal4 lines were used here to identify pigment-dispersing factor
      (PDF) and hugin-expressing neurons. We found that the large PDF expressing clock
      neurons only give rise to a single peptide, PDF. The three different classes of
      hugin expressing neurons all display the same mass signal, identical to pyrokinin
      2. The other peptide predicted from the hugin precursor, hugin gamma, was not
      detected in any of the cells. Single-cell peptidomics is a powerful tool in
      Drosophila neuroscience since Gal4 drivers can be produced for all known
      neuropeptide genes and thus provide detailed information about neuropeptide
      complements in neurons of interest.

PMID- 17439239
TI  - Role of a novel excipient poly(ethylene glycol)-b-poly(L-histidine) in retention
      of physical stability of insulin at aqueous/organic interface.
AB  - The aim of this study was to investigate whether a cationic polyelectrolyte,
      poly(ethylene glycol)-b-poly(L-histidine) diblock copolymer (PEG-polyHis), can
      stabilize insulin, at the aqueous/methylene chloride interface formed during the
      microencapsulation process. Insulin aggregation at this interface was monitored
      spectrophotometrically at 276 nm. The effects of protein concentration, pH of the
      aqueous medium, and the presence of poly(lactic-co-glycolic acid) (PLGA) in
      methylene chloride (MC) on insulin aggregation were observed. For the 2.0 mg/mL
      insulin solutions in phosphate buffer (PB), the effect of addition of Pluronic F
      127 as a positive control and addition of PEG-polyHis as a novel excipient in PB
      was also evaluated at various insulin/polymeric excipient weight ratios. The
      conformation of insulin protected by PEG-polyHis and recovered after interfacial
      exposure was evaluated via circular dichroism (CD) spectroscopy. Greater loss in
      soluble insulin was observed with increasing insulin concentrations. pH 6.0 was
      selected for optimal ionic interactions between insulin and PEG-polyHis based on
      zeta potential and particle size studies. pH 4.5 and 7.4 (no ionic complexation
      between insulin and PEG-polyHis) were selected as controls to compare the
      stabilization effect of PEG-polyHis with that at pH 6.0. Incubation of PEG
      polyHis with insulin at pH 6.0 drastically reduced protein aggregation, even in
      the presence of PLGA. PEG-polyHis and F-127 reduced insulin aggregation in
      noncomplexing pH conditions pointing to the role played by PEG in modulation of
      insulin adsorption at the interface. Far-UV (205-250 nm) CD study revealed
      negligible qualitative effects on soluble insulin's secondary structure after
      interfacial exposure. RP-HPLC and size-exclusion HPLC showed no deamidation of
      insulin or formation of soluble high molecular weight transformation products
      respectively. MALDI-TOF mass spectrometry confirmed the results from
      chromatographic procedures. Radioimmunoassay carried out on select samples showed
      that recovered soluble insulin had retained its immunoreactivity. An experimental
      method to simulate interfacial denaturation of proteins was designed for
      assessment of protein stability at the interface and screening for novel protein
      stabilizers. Understanding and manipulation of such polyelectrolyte-insulin
      complexation will likely play a role in insulin controlled delivery via
      microsphere formulation(s).

PMID- 17439241
TI  - Pressure balance at the liquid-liquid interface of micro countercurrent flows in
      microchips.
AB  - An interfacial pressure balance model was proposed and verified for the
      elucidation of the physical mechanism of micro countercurrent flow in a
      hydrophilic-hydrophobic selective-modification microchannel. We considered the
      conditions of the microflow phase separation, where the phase separation entails
      a single phase flow in each output of the microchannel. In this pressure balance
      model, the pressure difference between the two phases due to pressure loss in
      each phase is balanced by the Laplace pressure generated by the interfacial
      tension at the liquid-liquid interface between the separated phases. When the
      pressure difference between the two phases is sufficiently low, the contact line
      between the two phases is pinned at the boundary between the hydrophilic and the
      hydrophobic surfaces. Since the contact angle is restricted to values between the
      advancing and receding contact angles, the Laplace pressure has a limit. When the
      pressure difference between the two phases exceeds the limiting Laplace pressure,
      one of the phases leaks into the output channel of the other phase, and the phase
      separation fails. In order to experimentally verify this physical picture, a
      microchip with an asymmetric cross section, whose hydraulic diameters were 19 and
      102 mum, was used. In the microchip, a phase separation of a water-toluene micro
      countercurrent flow was achieved under pressure differences between an upper
      limit of 6.9 kPa and a lower limit of -9.3 kPa. The upper limit agreed well with
      the proposed model. The model is also applicable to cocurrent flows, so that it
      is useful for general multiphase microflows in continuous-flow chemical
      processing.

PMID- 17439242
TI  - Efficient and erroneous incorporation of oxidized DNA precursors by human DNA
      polymerase eta.
AB  - Altered oxidative metabolism is a property of many tumor cells. Oxidation of DNA
      precursors, i.e., dNTP pool, as well as DNA is a major source of mutagenesis and
      carcinogenesis. Here, we report the remarkable nature of human DNA polymerase eta
      that incorporates oxidized dNTPs into a nascent DNA strand in an efficient and
      erroneous manner. The polymerase almost exclusively incorporated 8-hydroxy-dGTP
      (8-OH-dGTP) opposite template adenine (A) at 60% efficiency of normal dTTP
      incorporation, and incorporated 2-hydroxy-dATP (2-OH-dATP) opposite template
      thymine (T), guanine (G), or cytosine (C) at substantial rates. The synthetic
      primers having 8-hydroxy-G paired with template A or 2-hydroxy-A paired with
      template T, G, or C at the termini were efficiently extended. In contrast, human
      DNA polymerase iota incorporated 8-OH-dGTP opposite template A with much lower
      efficiency and did not incorporate 2-OH-dATP opposite any of the template bases.
      It did not extend the primers having the oxidized bases at the termini either. We
      propose that human DNA polymerase eta may participate in oxidative mutagenesis
      through the efficient and erroneous incorporation of oxidized dNTPs during DNA
      synthesis.

PMID- 17439244
TI  - High-stability semiquinone intermediate in nitrate reductase A (NarGHI) from
      Escherichia coli is located in a quinol oxidation site close to heme bD.
AB  - Quinol/nitrate oxidoreductase (NarGHI) is the first enzyme involved in
      respiratory denitrification in prokaryotes. Although this complex in E. coli is
      known to operate with both ubi and menaquinones, the location and the number of
      quinol binding sites remain elusive. NarGHI strongly stabilizes a semiquinone
      radical located within the dihemic anchor subunit NarI. To identify its location
      and function, we used a combination of mutagenesis, kinetics, EPR, and ENDOR
      spectroscopies. For the NarGHIH66Y and NarGHIH187Y mutants lacking the distal
      heme bD, no EPR signal of the semiquinone was observed. In contrast, a
      semiquinone was detected in the NarGHIH56Y mutant lacking the proximal heme bP.
      Its thermodynamic properties and spectroscopic characteristics, as revealed by Q
      band EPR and ENDOR spectroscopies, are identical to those observed in the native
      enzyme. The substitution by Ala of the Lys86 residue close to heme bD, which was
      previously proposed to be in a quinol oxidation site of NarGHI (QD), also leads
      to the loss of the EPR signal of the semiquinone, although both hemes are
      present. Enzymatic assays carried out on the NarGHIK86A mutant reveal that the
      substitution dramatically reduces the rate of oxidation of both mena and
      ubiquinol analogues. These observations demonstrate that the semiquinone observed
      in NarI is strongly associated with heme bD and that Lys86 is required for its
      stabilization. Overall, our results indicate that the semiquinone is located
      within the quinol oxidation site QD. Details of the possible binding motif of the
      semiquinone and mechanistic implications are discussed.

PMID- 17439243
TI  - Oxidative folding and N-terminal cyclization of onconase.
AB  - Cyclization of the N-terminal glutamine residue to pyroglutamic acid in onconase,
      an anti-cancer chemotherapeutic agent, increases the activity and stability of
      the protein. Here, we examine the correlated effects of the folding/unfolding
      process and the formation of this N-terminal pyroglutamic acid. The results in
      this study indicate that cyclization of the N-terminal glutamine has no
      significant effect on the rate of either reductive unfolding or oxidative folding
      of the protein. Both the cyclized and uncyclized proteins seem to follow the same
      oxidative folding pathways; however, cyclization altered the relative flux of the
      protein in these two pathways by increasing the rate of formation of a
      kinetically trapped intermediate. Glutaminyl cyclase (QC) catalyzed the
      cyclization of the unfolded, reduced protein but had no effect on the disulfide
      intact, uncyclized, folded protein. The structured intermediates of uncyclized
      onconase were also resistant to QC catalysis, consistent with their having a
      native-like fold. These observations suggest that, in vivo, cyclization takes
      place during the initial stages of oxidative folding, specifically, before the
      formation of structured intermediates. The competition between oxidative folding
      and QC-mediated cyclization suggests that QC-catalyzed cyclization of the N
      terminal glutamine in onconase occurs in the endoplasmic reticulum, probably co
      translationally.

PMID- 17439245
TI  - Regulation of photoactivation in vertebrate short wavelength visual pigments:
      protonation of the retinylidene Schiff base and a counterion switch.
AB  - Xenopus violet cone opsin (VCOP) and its counterion variant (VCOP-D108A) are
      expressed in mammalian COS1 cells and regenerated with 11-cis-retinal. The
      phototransduction process in VCOP-D108A is investigated via cryogenic electronic
      spectroscopy, homology modeling, molecular dynamics, and molecular orbital
      theory. The VCOP-D108A variant is a UV-like pigment that displays less efficient
      photoactivation than the mouse short wavelength sensitive visual pigment (MUV)
      and photobleaching properties that are significantly different. Theoretical
      calculations trace the difference to the protonation state of the nearby glutamic
      acid residue E176, which is the homology equivalent of E181 in rhodopsin. We find
      that E176 is negatively charged in MUV but neutral (protonated) in VCOP-D108A. In
      the dark state, VCOP-D108A has an unprotonated Schiff base (SB) chromophore
      (lambdamax = 357 nm). Photolysis of VCOP-D108A at 70 K generates a bathochromic
      photostationary state (lambdamax = 380 nm). We identify two lumi intermediates,
      wherein the transitions from batho to the lumi intermediates are temperature- and
      pH-dependent. The batho intermediate decays to a more red-shifted intermediate
      called lumi I. The SB becomes protonated during the lumi I to lumi II transition.
      Decay of lumi II forms meta I, followed by the formation of meta II. We conclude
      that even in the absence of a primary counterion in VCOP-D108A, the SB becomes
      protonated during the photoactivation cascade. We examine the relevance of this
      observation to the counterion switch mechanism of visual pigment activation.

PMID- 17439246
TI  - Revealing the molecular determinants of neurotoxin specificity for calcium
      activated versus voltage-dependent potassium channels.
AB  - Potassium channel dysfunction underlies diseases such as epilepsy, hypertension,
      cardiac arrhythmias, and multiple sclerosis. Neurotoxins that selectively inhibit
      potassium channels, alpha-KTx, have provided invaluable information for
      dissecting the contribution of different potassium channels to neurotransmission,
      vasoconstriction, and lymphocyte proliferation. Thus, alpha-KTx specificity
      comprises an important first step in potassium channel-directed drug discovery
      for these diseases. Despite extensive functional and structural studies of alpha
      KTx-potassium channel complexes, none have predicted the molecular basis of alpha
      KTx specificity. Here we show that by minimizing the differences in binding free
      energy between selective and nonselective alpha-KTx we are able to identify all
      of the determinants of alpha-KTx specificity for calcium-activated versus voltage
      dependent potassium channels. Because these determinants correspond to unique
      features of the two types of channels, they provide a way to develop more
      accurate models of alpha-KTx-potassium channel complexes that can be used to
      design novel selective alpha-KTx inhibitors.

PMID- 17439247
TI  - The structure of testis angiotensin-converting enzyme in complex with the C
      domain-specific inhibitor RXPA380.
AB  - Angiotensin I-converting enzyme (ACE) is central to the regulation of the renin
      angiotensin system and is a key therapeutic target for combating hypertension and
      related cardiovascular diseases. Currently available drugs bind both active sites
      of its two homologous domains, although it is now understood that these domains
      function differently in vivo. The recently solved crystal structures of both
      domains (N and C) open the door to new domain-specific inhibitor design, taking
      advantage of the differences between these two large active sites. Here we
      present the first crystal structure at a resolution of 2.25 A of testis ACE
      (identical to the C domain of somatic ACE) with the highly C-domain-specific
      phosphinic inhibitor, RXPA380. Testis ACE retains the same conformation as seen
      in previously determined inhibitor complexes, but the RXPA380 central backbone
      conformation is more similar to that seen for the inhibitor captopril than
      enalaprilat. The RXPA380 molecule occupies more subsites of the testis ACE active
      site than the previously determined inhibitors and possesses bulky moieties that
      extend into the S2' and S2 subsites. Thus the high affinity of RXPA380 for the
      testis ACE/somatic ACE C domain is explained by the interaction of these bulky
      moieties with residues unique to these domains, specifically Phe 391, Val 379,
      and Val 380, that are not found in the N domain. The characterization of the
      extended active site and the binding of a potent C-domain-selective inhibitor
      provide the first structural data for the design of truly domain-specific
      pharmacophores.

PMID- 17439248
TI  - Hepatoprotective role of endogenous interleukin-13 in a murine model of
      acetaminophen-induced liver disease.
AB  - Recent evidence suggests that a deficiency in one or more hepatoprotective
      regulatory mechanisms may contribute to determining susceptibility in drug
      induced liver disease. In the present study, we investigated the role of
      interleukin (IL)-13 in acetaminophen (APAP)-induced liver disease (AILD).
      Following APAP (200 mg/kg) administration to male C57BL/6 wild-type (WT) mice,
      hepatotoxicity developed up to 24 h post-APAP, with a concomitant increase in
      serum IL-13 concentration. Pretreatment of these mice with an IL-13-neutralizing
      antibody exacerbated liver injury, as did APAP administration to IL-13 knockout
      (KO) mice in comparison to WT mice. No difference was observed in either overall
      APAP-protein adduct formation or liver glutathione levels between KO and WT mice
      following APAP administration, suggesting that the increased susceptibility of IL
      13 KO mice to AILD was not due to enhanced APAP bioactivation but rather
      injurious downstream events. In this regard, multiplex antibody arrays were used
      to identify potential IL-13-regulated biomarkers, including various cytokines and
      chemokines, as well as nitric oxide (NO), associated with AILD that were present
      at higher concentrations in the sera of APAP-treated IL-13 KO mice than in WT
      mice. Subsequent inhibition studies determined interferon-gamma, NO, neutrophils,
      natural killer cells, and natural killer cells with T-cell receptors had
      pathologic roles in AILD in IL-13 KO mice. Taken together, these results suggest
      that IL-13 is a critical hepatoprotective factor modulating the susceptibility to
      AILD and may provide hepatoprotection, in part, by down-regulating protoxicant
      factors and cells associated with the innate immune system.

PMID- 17439249
TI  - Decomposition of S-nitrosocysteine via S- to N-transnitrosation.
AB  - S-nitrosothiols are thought to be important intermediates in nitric oxide
      signaling pathways. These compounds are unstable, in part, through their ability
      to donate NO. One model S-nitrosothiol, S-nitrosocysteine, is particularly
      unstable. Recently, it was proposed that this compound decomposed via intra and
      intermolecular transfer of the NO group from the sulfur to the nitrogen to form N
      nitrosocysteine. This primary nitrosamine is expected to rapidly rearrange to
      ultimately form a reactive diazonium ion intermediate. To test this hypothesis,
      we demonstrated that thiirane-2-carboxylic acid is formed during the
      decomposition of S-nitrosocysteine at neutral pH. Acrylic acid was another
      product of this reaction. These results indicate that a small but significant
      amount of S-nitrosocysteine decomposes via S- to N-transnitrosation. The
      formation of a reactive intermediate in this process indicates the potential for
      this reaction to contribute to the toxicological properties of nitric oxide.

PMID- 17439251
TI  - Direct measurement of depletion and hydrodynamic forces in solutions of a
      reversible supramolecular polymer.
AB  - In this paper, the investigation of surface forces in semidilute solutions of a
      nonadsorbing hydrogen-bonded reversible supramolecular polymer is described.
      Colloidal probe atomic force microscopy was used for direct measurement of
      depletion forces. Hydrodynamic drag on the AFM cantilever with the colloidal
      probe was measured both far away from and close to the planar substrate surface.
      The results indicate that the presence of the depletion layer causes slip at the
      surfaces with a large apparent slip length. Our analysis explains how the
      presence of slip enables the measurement of (relatively weak) depletion forces in
      solutions with a high viscosity by significantly reducing the hydrodynamic
      forces. The range and magnitude of the measured depletion forces are
      qualitatively in agreement with previous experiments and theoretical predictions.
      Due to the relatively large experimental error, no quantitative conclusions can
      be drawn. Depletion-induced phase separation of suspensions of stearylated silica
      particles was also observed. Phase separation becomes more pronounced with
      increasing polymer concentration.

PMID- 17439250
TI  - Mechanosensing using drag force for imaging soft biological membranes.
AB  - We investigate physical processes taking place during nanoscale mechanosensing of
      soft biological membranes in liquid environments. Examples include tapping mode
      imaging by atomic force microscope (AFM) and microscopy based on the Brownian
      motion of a nanoparticle in an optical-tweezers-controlled trap. The softness and
      fluidity of the cellular membrane make it difficult to accurately detect (i.e.,
      image) the shape of the cell using traditional mechanosensing methods. The aim of
      the reported work is to theoretically evaluate whether the drag force acting on
      the nanoscale mechanical probe due to a combined effect of intra- and
      extracellular environments can be exploited to develop a new imaging mode
      suitable for soft cellular interfaces. We approach this problem by rigorous
      modeling of the fluid mechanics of a complex viscoelastic biosystem in which the
      probe sensing process is intimately coupled to the membrane biomechanics. The
      effects of the probe dimensions and elastic properties of the membrane as well as
      intra- and extracellular viscosities are investigated in detail to establish the
      structure and evolution of the fluid field as well as the dynamics of membrane
      deformation. The results of numerical simulations, supported by predictions of
      the scaling analysis of forces acting on the probe, suggest that viscous drag is
      the dominant force dictating the probe dynamics as it approaches a biological
      interface. The increase in the drag force is shown to be measurable, to scale
      linearly with an increase in the viscosity ratio of the fluids on either side of
      the membrane, and to be inversely proportional to the probe-to-membrane distance.
      This leads to the postulation of a new strategy for lipid membrane imaging by AFM
      or other mechanosensing methods using a variation in the maximum drag force as an
      indicator of the membrane position.

PMID- 17439252
TI  - Self-assembling DNA dendrimers: a numerical study.
AB  - DNA is increasingly used as a specific linker to template nanostructured
      materials. We present a molecular dynamics simulation study of a simple DNA
      dendrimer model designed to capture the basic characteristics of the biological
      interactions, where selectivity and strong cooperativity play an important role.
      Exploring a large set of densities and temperatures, we follow the progressive
      formation of a percolating large-scale network whose connectivity can be
      described by random percolation theory. We identify the relative regions of
      network formation and kinetic arrest versus phase separation and show that the
      location of the two-phase region can be interpreted in the same framework as
      reduced valency models. This correspondence provides guidelines for designing
      stable, equilibrium self-assembled low-density networks. Finally, we demonstrate
      a relation between bonding and dynamics, by showing that the temperature
      dependence of the diffusion constant is controlled by the number of fully
      unbonded dendrimers.

PMID- 17439253
TI  - Mechanistic insights into the proline-directed enantioselective heterogeneous
      hydrogenation of isophorone.
AB  - The adsorption rates onto a range of platinum single-crystal surfaces of key
      species involved in the proline-directed heterogeneous enantioselective
      hydrogenation of isophorone were investigated by electrochemical means.
      Specifically, the uptakes of the prochiral reactant (isophorone), the chiral
      hydrogenation product (3,3,5-trimethylcyclohexanone), and the chiral directing
      agent ((R)- and (S)-proline) were examined. The effects of R,S chiral kink sites
      on the adsorption of (R,S)-proline were also studied. The reactant adsorbs
      approximately 105 times faster than the chiral modifier so that under conditions
      of competitive adsorption the latter is entirely excluded from the metal surface.
      Supplementary displacement and reaction rate measurements carried out with
      practical Pd/carbon catalysts show that under certain reaction conditions
      isophorone quickly displaces preadsorbed proline from the metal surface. Thus
      both kinetics and thermodynamics ensure that the chiral modifier can play no role
      in any surface-mediated process that leads to enantiodifferentiation. These
      results are fully consistent with the recent proposal1 that the crucial step
      leading to enantiodifferentiation occurs in the solution phase and not at the
      metal surface. In addition, it is found that there is no preferred diastereomeric
      interaction between (R,S)-proline and R,S step kink sites on Pt{643} and Pt{976},
      implying that such sites do not play a role in determining the catalytic behavior
      of supported metal nanoparticles.

PMID- 17439254
TI  - Electrochemiluminescence of Ru(II) complexes immobilized on a magnetic microbead
      surface: distribution of magnetic microbeads on the electrode surface and effect
      of azide ion.
AB  - The electrochemiluminescence (ECL) of magnetic microbeads modified with tris(2,2'
      bipyridine)ruthenium(II) ([Ru(bpy)3]2+) was studied in the presence of tri-n
      propylamine (TPA) to develop highly sensitive ECL detection system, where the
      employed microbead has a diameter of 4.5 microm. The ECL signal of the
      [Ru(bpy)3]2+ derivative-modified magnetic microbeads was found to be affected by
      the geometrical distribution of the magnetic microbeads on the electrode surface.
      The ECL peak intensity increased with increasing the number of the beads on the
      electrode surfaces up to 1.6 x 10(6) beads cm(-2), although above 1.6 x 10(6)
      beads cm(-2), it decreased. The ECL decrease arises from the physical prevention
      of the ECL from reaching the photomultiplier tube by the excessive beads. The
      observed peak ECL signal of the [Ru(bpy)3]2+ derivative-modified magnetic
      microbeads in the presence of NaN3, which serves as a preservative substance,
      mainly appeared at a potential of +0.90 V vs Ag/AgCl where [Ru(bpy)3]2+ is hardly
      oxidized, whereas the ECL signal in the absence of NaN3 appeared at a potential
      of +1.15 V. The presence of NaN3 on the electrode surface retards formation of an
      oxide layer on the electrode surfaces and promotes TPA oxidation. The ECL
      response at +0.90 V was mainly attributed to ECL reaction of excited-state
      [Ru(bpy)3]2+* formed by oxidation of [Ru(bpy)3]+ with TPA radical cation, where
      the [Ru(bpy)3]+ was generated by reduction of [Ru(bpy)3]2+ with TPA radical.

PMID- 17439255
TI  - Template-derived mesoporous carbons with highly dispersed transition metals as
      media for the reactive adsorption of dibenzothiophene.
AB  - Mesoporous carbons with highly dispersed copper, cobalt, and iron were obtained
      from an organic polymer within amorphous silica powder, alumina, and zeolite 13X.
      The materials were characterized using the adsorption of nitrogen, potentiometric
      titration, and elemental analysis. The small metal content (less than 1%) and its
      chelation in the precursor polymers ensure a high dispersion of metallic centers.
      The materials obtained are mainly mesoporous but differ significantly in their
      porosity and surface chemistry, which is linked to the effect of template
      constraints and chemistry and the kind of metal and is related to the differences
      in the carbonization mechanism. On the carbon obtained, the adsorption of
      dibenzothiophene (DBT) from hexane was carried out. The high capacities (up to
      130 mg S/g) obtained were linked to the high volume of mesopores and specific
      interactions of DBT with surface acidic groups and strong interactions of metals
      with dibenzothiophene via S-M sigma bonds or, in the case of copper, via
      interaction of metals with disturbed pi electrons of aromatic rings of DBT.

PMID- 17439256
TI  - Stable amphoteric nanogels made of ovalbumin and ovotransferrin via self
      assembly.
AB  - Ovalbumin and ovotransferrin are two proteins in hen egg white with isoelectric
      points of 4.8 and 6.8, respectively. A convenient and green method was developed
      in this study to prepare ovalbumin-ovotransferrin nanogels: a mixture of the two
      proteins was adjusted to a certain pH and then heated. Heat induced denaturation
      and gelation of the proteins, but the negative charges of ovalbumin prevented the
      proteins from coagulating. Dynamic light scattering, transmission electron
      microscopy, and atomic force microscopy studies reveal the nanogels have a
      spherical shape in both the swell and dry forms. Their apparent hydrodynamic
      diameters are in the range of 100-220 nm depending on the protein concentration
      in the nanogel preparation process. The nanogels display an amphoteric property:
      they carry net positive charges at pH lower than 5.5 and net negative charges at
      pH higher than 5.5. They form redispersible secondary aggregates at pH 5.0-6.0.
      The nanogels are stable in the pH ranges of 2.0-4.0 and 7.0-11.0, and they
      exhibit pH unchangeable but thermoreversible hydrophobicity. Benzoic acid was
      used as a model drug to study the loading ability. The native ovalbumin and
      ovotransferrin cannot bind with benzoic acid, whereas the nanogels with the
      network structure and hydrophobic binding sites can load benzoic acid through
      hydrophobic and electrostatic interactions.

PMID- 17439257
TI  - Emulsification of partially miscible liquids using colloidal particles:
      nonspherical and extended domain structures.
AB  - We present microscopy studies of particle-stabilized emulsions with
      unconventional morphologies. The emulsions comprise pairs of partially miscible
      fluids and are stabilized by colloids. Alcohol-oil mixtures are employed; silica
      colloids are chemically modified so that they have partial wettability. We create
      our morphologies by two distinct routes: starting with a conventional colloid
      stabilized emulsion or starting in the single-fluid phase with the colloids
      dispersed. In the first case temperature cycling leads to the creation of
      extended fluid domains built around some of the initial fluid droplets. In the
      second case quenching into the demixed region leads to the formation of domains
      which reflect the demixing kinetics. The structures are stable due to a jammed,
      semisolid, multilayer of colloids on the liquid-liquid interface. The differing
      morphologies reflect the roles in formation of the arrested state of
      heterogeneous and homogeneous nucleation and spinodal decomposition. The latter
      results in metastable, bicontinuous emulsions with frozen interfaces, at least
      for the thin-slab samples, investigated here.

PMID- 17439258
TI  - Molecular macrocluster formation on silica surfaces in phenol-cyclohexane
      mixtures.
AB  - The adsorption of phenol, an aromatic compound with a hydrogen-bonding group,
      onto a silica surface in cyclohexane was investigated by colloidal probe atomic
      force microscopy (AFM), attenuated total reflection Fourier transform infrared
      spectroscopy (ATR-FTIR), and adsorption isotherm measurements. ATR-FTIR
      measurements on the silica surface indicated the formation of surface
      macroclusters of phenol through hydrogen bonding. The ATR-FTIR spectra were also
      measured on the H-terminated silicon surface to observe the effect of the silanol
      groups on the phenol adsorption. The comparison of the ATR-FTIR spectra for both
      the silicon oxide and H-terminated silicon surfaces proved that the silanol
      groups are necessary for the formation of phenol clusters on the surface. The
      surface force measurement using colloidal probe AFM showed a long-range
      attraction between the two silica surfaces in phenol-cyclohexane mixtures. This
      long-range attraction resulted from the contact of the adsorbed phenol layers for
      the phenol concentrations below 0.6 mol %, at which no significant phenol
      clusters formed in the bulk solution. The attraction started to decrease at 0.6
      mol % phenol due to the exchange of the phenol molecules between the clusters in
      the bulk phase and on the surface. The surface density of phenol in the adsorbed
      layer was calculated on the basis of the long-range attraction and found to be
      much smaller than the liquid phenol density. The plausible structure of the
      adsorbed phenol layer was drawn by referring to the crystal structure of the bulk
      phenol and orientation of the phenol molecules on the surface, estimated by the
      dichroic analysis of ATR-FTIR spectroscopy. The investigation of the phenol
      adsorption on the silica surface in a nonpolar solvent using this novel approach
      demonstrated the effect of the aromatic ring on the surface packing density.

PMID- 17439259
TI  - Sodium polyacrylate adsorption onto anionic and cationic silica in the presence
      of salts.
AB  - Sodium polyacrylate is well known for its application as a scale inhibitor in
      common household products, and the effects of both monovalent and divalent metal
      cations on its structure have been covered by a range of previous publications.
      In the present article, we extend this work by using solvent relaxation NMR to
      look at the adsorption of the polyelectrolyte onto both positively and negatively
      charged silica and how this is altered by calcium chloride. In the anionic case,
      we found that polyacrylate adsorption was predictably very weak, and
      interestingly, perhaps counterintuitively, it was further reduced by calcium
      ions. This is probably linked to NaPA-Ca2+ binding, which changes the
      conformation and charge of the polyelectrolyte. In contrast, NaPA adsorbs very
      strongly on cationic silica, to the point that precipitation often occurs,
      particularly on addition of salt.

PMID- 17439260
TI  - Rupture force analysis and the associated systematic errors in force spectroscopy
      by AFM.
AB  - Force spectroscopy is a new and valuable tool in physical chemistry and
      biophysics. However, data analysis has yet to be standardized, hindering the
      advancement of the technique. In this article, treatment of the rupture forces is
      described in the framework of the Bell-Evans model, and the systematic errors
      associated with the tether effect for approaches that utilize the most probable,
      the median, and the mean rupture forces are compared. It is shown that
      significant systematic errors in the dissociation rate can result from nonlinear
      loading with polymeric tethers even if the apparent loading rate is used in the
      analysis. Analytical expressions for the systematic errors are provided for the
      most probable and median forces. The use of these expressions to correct the
      associated systematic errors is illustrated by the analysis of the measured
      rupture forces between single hexadecane molecules in water. It is noted that the
      measured distributions of rupture forces often contain high forces that are
      unaccounted for by theoretical models. Experimental data indicate that the most
      significant effect of the high forces "tail" is on the dissociation rate obtained
      from the median force analysis whereas the barrier width appears to be
      unaffected.

PMID- 17439261
TI  - Nanostructured copper phthalocyanine-sensitized multiwall carbon nanotube films.
AB  - We report a detailed study of the interaction between surface-oxidized multiwall
      carbon nanotubes (o-MWCNTs) and the molecular semiconductor tetrasulfonate copper
      phthalocyanine (TS-CuPc). Concentrated dispersions of o-MWCNT in aqueous
      solutions of TS-CuPc are stable toward nanotube flocculation and exhibit
      spontaneous nanostructuring upon rapid drying. In addition to hydrogen-bonding
      interactions, the compatibility between the two components is shown to result
      from a ground-state charge-transfer interaction with partial charge transfer from
      o-MWCNT to TS-CuPc molecules orientated such that the plane of the macrocycle is
      parallel to the nanotube surface. The electronegativity of TS-CuPc as compared to
      unsubsubtituted copper phthalocyanine is shown to result from the electron
      withdrawing character of the sulfonate substituents, which increase the molecular
      ionization potential and promote cofacial molecular aggregation upon drying. Upon
      spin casting to form uniform thin films, the experimental evidence is consistent
      with an o-MWCNT scaffold decorated with phthalocyanine molecules self-assembled
      into extended aggregates reminiscent of 1-D linearly stacked phthalocyanine
      polymers. Remarkably, this self-organization occurs in a fraction of a second
      during the spin-coating process. To demonstrate the potential utility of this
      hybrid material, it is successfully incorporated into a model organic
      photovoltaic cell at the interface between a poly(3-hexylthiophene):[6,6]-phenyl
      C61 butyric acid methyl ester bulk heterojunction layer and an indium-tin oxide
      coated glass electrode to increase the light-harvesting capability of the device
      and facilitate hole extraction. The resulting enhancement in power conversion
      efficiency is rationalized in terms of the electronic, optical, and morphological
      properties of the nanostructured thin film.

PMID- 17439262
TI  - Fabrication and electrochemical investigation of layer-by-layer deposited
      titanium phosphate/Prussian blue composite films.
AB  - Composite films of titanium phosphate (TiPS)/Prussian blue (PB) were fabricated
      by the alternative deposition of TiPS layer and PB nanocrystals. The layer of
      TiPS was fabricated by adsorption of hydrated titanium from aqueous Ti(SO4)2
      solution and subsequent reaction with phosphate groups. The layer of PB
      nanocrystals was fabricated by sequential adsorption of FeCl3 solution and
      K4[Fe(CN)6] solution. Regular deposition of TiPS/PB composite films were verified
      by UV-vis absorption spectroscopy and quartz crystal microbalance measurements.
      The successful fabrication of the TiPS/PB composite films was further confirmed
      by X-ray photoelectron spectroscopy and Fourier transform infrared (FT-IR)
      spectroscopy. Instead of producing films of TiPS layers alternating with PB
      nanocrystal layers, the TiPS/PB composite films have a structure in which the
      interstices of the PB nanocrystal films are filled with TiPS component. TiPS/PB
      composite films show enhanced electrochemical properties and improved stability
      in comparison with pure PB films prepared by the multiple sequential adsorption
      process. TiPS/PB composite films have the capability to catalyze the
      electrochemical reduction of H2O2 and can be used as a biosensor for detecting
      H2O2.

PMID- 17439263
TI  - The epidermis of scales in gecko lizards contains multiple forms of beta-keratins
      including basic glycine-proline-serine-rich proteins.
AB  - The epidermis of scales of gecko lizards comprises alpha- and beta-keratins.
      Using bidimensional electrophoresis and immunoblotting, we have characterized
      keratins of corneous layers of scales in geckos, especially beta-keratins in
      digit pad lamellae. In the latter, the formation of thin bristles (setae) allow
      for the adhesion and climbing vertical or inverted surfaces. alpha-Keratins of 55
      66 kDa remain in the acidic and neutral range of pI, while beta-keratins of 13-18
      kDa show a broader variation of pI (4-10). Some protein spots for beta-keratins
      correspond to previously sequenced, basic glycine-proline-serine-rich beta
      keratins of 169-191 amino acids. The predicted secondary structure shows that a
      large part of the molecule has a random-coiled conformation, small alpha helix
      regions, and a central region with 2-3 strands (beta-folding). The latter, termed
      core-box, shows homology with feather-scale-claw keratins of birds and is
      involved in the formation of beta-keratin filaments. Immunolocalization of beta
      keratins indicates that these proteins are mainly present in the beta-layer and
      oberhautchen layer, including setae. The sequenced proteins of setae form bundles
      of keratins that determine their elongation. This process resembles that of
      feather-keratin on the elongation of barbule cells in feathers. It is suggested
      that small proteins rich in glycine, serine, and proline evolved in reptiles and
      birds to reinforce the mechanical resistance of the cytokeratin cytoskeleton
      initially present in the epidermis of scales and feathers.

PMID- 17439264
TI  - Dielectric saturation of the ion hydration shell and interaction between two
      double helices of DNA in mono- and multivalent electrolyte solutions: foundations
      of the epsilon-modified Poisson-Boltzmann theory.
AB  - Potentials of mean force between single Na+, Ca2+, and Mg2+ cations and a highly
      charged spherical macroion in SPC/E water have been determined using molecular
      dynamics simulations. Results are compared to the electrostatic energy
      calculations for the primitive polarization model (PPM) of hydrated cations
      describing the ion hydration shell as a dielectric sphere of low permittivity
      (Gavryushov, S.; Linse, P. J. Phys. Chem. B 2003, 107, 7135). Parameters of the
      ion dielectric sphere and radius of the macroion/water dielectric boundary were
      extracted by means of this comparison to approximate the short-range repulsion of
      ions near the interface. To explore the counterion distributions around a
      simplified model of DNA, the obtained PPM parameters for Na+ and Ca2+ have been
      substituted into the modified Poisson-Boltzmann (MPB) equations derived for the
      PPM and named the epsilon-MPB (epsilon-MPB) theory. epsilon-MPB results for DNA
      suggest that such polarization effects are important in the case of 2:1
      electrolyte and highly charged macromolecules. The three-dimensional
      implementation of the epsilon-MPB theory was also applied to calculation of the
      energies of interaction between two parallel macromolecules of DNA in solutions
      of NaCl and CaCl2. Being compared to results of MPB calculations without the ion
      polarization effects, it suggests that the ion hydration shell polarization and
      inhomogeneous solvent permittivity might be essential factors in the
      experimentally known hydration forces acting between charged macromolecules and
      bilayers at separations of less than 20 A between their surfaces.

PMID- 17439265
TI  - Theoretical prediction of the p53 gene mutagenic mechanism induced by trans-4
      hydroxy-2-nonenal.
AB  - The reaction mechanism of guanine with trans-4-hydroxyl-2-nonenal (4-HNE) and the
      mutagenic mechanism induced by adducts have been theoretically predicted at a
      molecular level from the energy point of view. 4-HNE directly reacts with guanine
      via three steps, yielding eventually four main diastereoisomers: trans-4-HNE-dG
      adducts. A concerted six-atom-centered transition state is proposed for the first
      step, while the last two steps are involved in four-membered-ring transition
      states. The third step is the rate-determining step. The studies of base pairing
      properties of trans-4-HNE-dG adducts with A, T, C, A*, and T* together with the
      relationship between the mutation and structure of trans-4-HNE-dG indicate that
      syn- and anti-conformations of trans-4-HNE-dG around the glycosidic bond are
      favorable for pairing with A* and T*, respectively, in the parental generation.
      As a result, the GC --> CG or GC --> TA mutation may be generated from the syn-4
      HNE-dGA* during replication. Nevertheless, anti-4-HNE-dGT* creates GC --> TA
      mutation or nonmutagenesis. Moreover, syn-4-HNE-dGA* has a slightly higher
      probability to be generated than anti-4-HNE-dGT* in the parental generation;
      therefore, the GC to TA transversion is predominant among the mutations. In
      addition, no correlation between the mutations and the stereochemistry of C6 and
      C8 of trans-4-HNE-dG adducts was found in this work. Our mutational results have
      interpreted well a part of the discrete experimental observations, but the
      mutagenic process itself has not previously been characterized, through either
      computation or experiment.

PMID- 17439266
TI  - Triplet formation of 4-thiothymidine and its photosensitization to oxygen studied
      by time-resolved thermal lensing technique.
AB  - Excited-state dynamics of 4-thiothymidine (S4-TdR) and its photosensitization to
      molecular oxygen in solution with UVA irradiation were investigated. Absorption
      and emission spectra measurements revealed that UVA photolysis of S4-TdR gives
      rise to a population of T1(pipi*), following S2(pipi*) --> S1(npi*) internal
      conversion. In transient absorption measurement, the 355 nm laser photolysis gave
      broad absorption (380-600 nm) bands of triplet S4-TdR. The time-resolved thermal
      lensing (TRTL) signal of S4-TdR containing the thermal component due to decay of
      triplet S4-TdR was clearly observed by the 355 nm laser excitation. The quantum
      yield for S1 --> T1 intersystem crossing was estimated to be unity by a triplet
      quenching experiment with potassium iodide. In the presence of molecular oxygen,
      the photosensitization from triplet S4-TdR gave rise to singlet oxygen O2
      (1Deltag) with a quantum yield of 0.50. Therapeutic implications of such singlet
      oxygen formation are discussed.

PMID- 17439267
TI  - Conformational preferences and cis-trans isomerization of azaproline residue.
AB  - The conformational study of N-acetyl-N'-methylamide of azaproline (Ac-azPro-NHMe,
      the azPro dipeptide) is carried out using ab initio HF and density functional
      methods with the self-consistent reaction field method to explore the effects of
      the replacement of the backbone CHalpha group by the nitrogen atom on the
      conformational preferences and prolyl cis-trans isomerization in the gas phase
      and in solution (chloroform and water). The incorporation of the Nalpha atom into
      the prolyl ring results in the different puckering, backbone population, and
      barriers to prolyl cis-trans isomerization from those of Ac-Pro-NHMe (the Pro
      dipeptide). In particular, the azPro dipeptide has a dominant backbone
      conformation D (beta2) with the cis peptide bond preceding the azPro residue in
      both the gas phase and solution. This may be ascribed to the favorable
      electrostatic interaction or intramolecular hydrogen bond between the prolyl
      nitrogen and the amide hydrogen following the azPro residue and to the absence of
      the unfavorable interactions between electron lone pairs of the acetyl carbonyl
      oxygen and the prolyl Nalpha. This calculated higher population of the cis
      peptide bond is consistent with the results from X-ray and NMR experiments. As
      the solvent polarity increases, the conformations B and B* with the trans peptide
      bond become more populated and the cis population decreases more, which is
      opposite to the results for the Pro dipeptide. The conformation B lies between
      conformations D and A (alpha) and conformation B* is a mirror image of the
      conformation B on the phi-psi map. The barriers to prolyl cis-trans isomerization
      for the azPro dipeptide increase with the increase of solvent polarity, and the
      cis-trans isomerization proceeds through only the clockwise rotation with omega'
      approximately +120 degrees about the prolyl peptide bond for the azPro dipeptide
      in the gas phase and in solution, as seen for the Pro dipeptide. The pertinent
      distance d(N...H-NNHMe) and the pyramidality of imide nitrogen can describe the
      role of this hydrogen bond in stabilizing the transition state structure and the
      lower rotational barriers for the azPro dipeptide than those for the Pro
      dipeptide in the gas phase and in solution.

PMID- 17439268
TI  - Fluorescence probing of temperature-dependent dynamics and friction in ionic
      liquid local environments.
AB  - The solvation dynamics and local orientational friction for a series of four
      ionic liquids have been probed using coumarin 153 (C153) as a function of
      temperature. These ionic liquids are comprised of nonaromatic organic cations
      paired with a common anion, bis(trifluoromethylsulfonyl)imide (NTf(2)-). The
      specific liquids are as follows: N-methyl-tri-N-butylammonium NTf(2)-
      (N(1444)+/NTf(2)-), N-hexyl-tri-N-butylammonium NTf(2)- (N(6444)+/NTf(2)-), N
      methyl-N-butylpyrrolidinium NTf(2)- (Pyrr(14)+/NTf(2)-), and N-methyl-N
      ethoxyethylpyrrolidinium NTf(2)- (Pyrr(1(2O2))+/NTf(2)-). The observed solvation
      dynamics and fluorescence depolarization dynamics occur over a broad range of
      time scales that can only be adequately fit by functions including three or more
      exponential components. Stretched exponential distributions cannot adequately fit
      our data. The solvation and reorientational dynamics of the C153 probe are
      studied over a range of temperatures from 278.2 to 353.2 K. For both the
      solvation dynamics and the probe reorientational dynamics, the observed
      temperature dependence is well fit by a Vogel-Tammann-Fulcher law. To correlate
      the observed microscopic dynamics with macroscopic physical properties,
      temperature-dependent viscosities are also measured. Differential scanning
      calorimetry is used to study the thermodynamics of the phase transitions from the
      liquid to supercooled liquid to glassy states. For the two tetraalkylammonium
      liquids, the observed melting transitions occur near 300 K, so we are able to
      study the dynamics in a clearly supercooled regime. Very long time scale
      orientational relaxation time constants dynamics on the order of 100 ns are
      observed in the C153 fluorescence anisotropy. These are interpreted to arise from
      long-lived local structures in the environment surrounding the C153 probe.

PMID- 17439269
TI  - Alkyl and dendron substituted quinacridones: synthesis, structures, and
      luminescent properties.
AB  - The synthesis of two alkyl substituted quinacridone derivatives, N,N'-di(n-hexyl)
      1,3,8,10-tetramethylquinacridone (1) and N,N'-di(n-hexyl)-2,9-di(t
      butyl)quinacridone (2), and four dendritic quinacridone derivatives, N,N'
      didendritic-1,3,8,10-tetramethylquinacridones (3-G1 and 3-G2) and N,N'
      didendritic-2,9-di(tert-butyl)quinacridones (4-G1 and 4-G2) are reported. X-ray
      crystal structure and thermal analysis revealed that the quinacridone derivatives
      reported in this paper exhibit the evolution from crystalline phase to amorphous
      phase upon varying from alkyl substituted quinacridones to dendritic
      quinacridones. The concentration-dependent 1H NMR, UV-vis, and photoluminescence
      (PL) spectroscopic studies demonstrated the aggregation properties of the
      quinacridone derivatives in solution. For dendritic quinacridones with the
      sufficient shield of dendrons, the fluorescence concentration quenching can be
      significantly suppressed and emission intensity in concentrated solution and
      solid state could be greatly enhanced. Compound 4-G2 displays good solution
      process property and higher PL yield in concentrated solution, suggesting that it
      is a potential candidate for the fabrication of high-performance organic
      electroluminescent devices (OLEDs) on the basis of low-cost solution process
      technique.

PMID- 17439270
TI  - Atomistic mechanisms of phase separation and formation of solid solutions: model
      studies of NaCl, NaCl-NaF, and Na(Cl1-xBrx) crystallization from the melt.
AB  - The crystallization of sodium chloride from its melt and mixtures with other
      sodium halides is investigated by means of transition path sampling molecular
      dynamics simulations. From this we explore the nucleation mechanisms of both the
      solidification and the melting process at the atomistic level of detail. By
      incorporation of impurities the nucleation picture of the eutectic mixtures
      changes considerably. Doping the NaCl crystal with fluoride ions, we observed the
      substitutional defects to act as favored nucleation centers for the melting
      transition. This phenomenon plays a critical role during the solidification
      process of NaCl-NaF melts of low NaF concentration and is demonstrated to account
      for the segregation of fluoride ions. While NaCl-NaF corresponds to a eutectic
      system, we also investigated NaCl-NaBr mixtures. The bromide ions were observed
      to behave very similarly to chloride ions. As a consequence, no phase separation
      occurs and Na(Cl1-xBrx) solid solutions are formed. At the example of these two
      prototypes we demonstrate the study of the atomistic mechanisms related to phase
      separation processes and solid solution formation during the nucleation and
      growth of crystals from multinary melts.

PMID- 17439271
TI  - Contrasts in the 77 K emission spectra, structures, and dynamics of metal-to
      metal and metal-to-ligand charge-transfer excited states.
AB  - The 77 K emission spectrum of trans-[(ms-Me6[14]aneN4)Cr(CNRu(NH3)5)2]5+ has
      components characteristic of ligand field (LF) and metal-to-metal charge transfer
      (MMCT) excited states (ms-Me6[14]aneN4=5,12-meso-5,7,7,12,14,14-hexamethyl
      1,4,8,11-tetraazacyclotetradecane). The LF component of the emission is best
      resolved for irradiations at appreciably higher energies than the MMCT absorption
      band, while only the MMCT emission is observed for irradiations on the low-energy
      side of the MMCT absorption band. The LF emission component from this complex has
      vibronic structure that is very similar to that of the trans-[(ms
      Me6[14]aneN4)Cr(CN)2]+ parent, but it is red-shifted by 560 cm-1 and the
      bandwidths are much larger. The red shift and the larger bandwidths of the
      ruthenated complex are attributed to configurational mixing between the LF and
      MMCT excited states, and the inferred mixing parameters are shown to be
      consistent with the known electron-transfer properties of the Ru(NH3)5 moieties.
      The MMCT excited-state lifetime is about 1 micros at 77 K and am(m)ine
      perdeuteration of this complex leads to an isotope effect of kNH/kND
      approximately 15-20. However, the contribution of the N-H stretching vibration to
      the emission sideband is too weak for a single vibrational mode model to be
      consistent with the observed lifetimes or the isotope effect. These features are
      very similar to those reported previously (J. Phys. Chem. A 2004, 108, 5041) for
      the MMCT emission of trans-[([14]aneN4)Cr{CNRu(NH3)5}2]5+ ([14]aneN4=1,4,8,11
      tetraazacyclotetradecane), with the exception that the higher energy LF emission
      was not well resolved in the earlier work. The energies of the charge transfer
      absorption and emission maxima of both of these Cr(CN)Ru complexes are very
      similar to those of [Ru(NH3)4bpy]2+, but the latter has a 50-fold shorter 77 K
      excited-state lifetime, a 10-fold smaller NH/ND isotope effect, and a very
      different structure of its vibronic sidebands. Thus, the vibronic sidebands imply
      that the dominant excited-state distortions are in the metal-ligand vibrational
      modes for the Cr(CN)Ru complexes and in the bipyridine vibrational modes for the
      [Ru(NH3)4bpy]2+ complex. While an "equivalent" single vibrational mode model
      based on the frequencies and amplitudes of the dominant distortion modes is not
      consistent the observed lifetimes, such models do appear to be a good basis for
      qualitatively distinguishing different classes of excited-state dynamic behavior.
      A multimode, multichannel model may be necessary to adequately describe the
      excited-state dynamics of these simple electron-transfer systems.

PMID- 17439272
TI  - Origins of cooperative noncovalent host-guest chemistry in mixed valence
      complexes.
AB  - The electronic effects resulting from noncovalent host-guest interactions between
      calix[6]arene and a ruthenium dimer, [Ru3O(OAc)6(CO)(ppy)]2-mu-pz (ppy=4-phenyl
      pyridine, pz=pyrazine), are presented. The noncovalent interaction is between the
      calix[6]arene and the ppy ligands of the dimer. The dimer can bind 2 equiv of
      calix[6]arene. The complex [Ru3O(OAc)6(CO)(ppy)]2-mu-pz forms a highly stable
      mixed valence ion with strong electronic coupling between the two Ru3 clusters.
      The strength of the electronic interaction is found to be moderated by
      calix[6]arene binding. Addition of calix[6]arene to the mixed valence ion causes
      the electronic coupling to decrease. The binding of calix[6]arene is found to be
      cooperative. The origins of cooperative binding are developed in terms of the
      potential energy surfaces associated with the symmetric and asymmetric mixed
      valence ion. In particular, it is found that symmetry breaking (through the
      binding of a single calix[6]arene) destabilizes the mixed valence state.
      Restoration of symmetry (through the binding of a second calix[6]arene) increases
      the stability of the mixed valence ion and provides an additional driving force
      for the binding of the second calix[6]arene.

PMID- 17439273
TI  - Structural isotopic effects in the smallest chiral amino acid: observation of a
      structural phase transition in fully deuterated alanine.
AB  - A first study of possible changes instigated by deuteration in amino acids was
      carried out using neutron diffraction, inelastic neutron scattering, and Raman
      scattering in l-alanine, C2H4(NH2)COOH. Careful analysis of the structural
      parameters shows that deuteration of l-alanine engenders significant geometric
      changes as a function of temperature, which can be directly related to the
      observation of new lattice vibration modes in the Raman spectra. The combination
      of the experimental data suggests that C2D4(ND2)COOD undergoes a structural phase
      transition (or a structural rearrangement) at about 170 K. Considering that this
      particular amino acid is a hydrogen-bonded system with short hydrogen bonds
      (O...H approximately 1.8 A), we evoke the Ubbelohde effect to conclude that
      substitution of hydrogen for deuterium gives rise to changes in the hydrogen
      bonding interactions. The structural differences suggest distinct relative
      stabilities for the hydrogenous and deuterated l-alanine.

PMID- 17439274
TI  - Thermodynamic characterization of rare Earth salts of strong polyacid copolymers.
AB  - Stoichiometric La3+, Ce3+, and Nd3+ salts of poly[(vinyl alcohol)-co-(vinyl
      sulfate)] (PVAS) copolymer polyacids have been studied in aqueous solution
      without added salt. All LnPVAS salts were entirely water-soluble in the
      composition and concentration range investigated. Ratios of the vinyl sulfate and
      vinyl alcohol units in the copolymers were between 1:5 and 1:107, leading to
      structural charge densities both above and under the critical value needed for
      counterion condensation of trivalent counterions. Solvent activity, a1, has been
      measured by the gel deswelling method in the concentration range of 5 x 10(-4) to
      1 x 10(-1) mol of counterion/kg of water (0.2-9 w/w% of the polyelectrolyte).
      Results are unusually high for polyelectrolytes (-2 x 10(-6) > ln a1 > -3 x 10(
      4)), and they are comparable with values determined in solutions of uncharged
      polymers. Nevertheless, the different copolymers can be clearly distinguished;
      the water activity is lowered in the order of the vinyl sulfate content of the
      polyelectrolytes, except for the one above the critical charge density. No
      observable difference was caused in the thermodynamic properties by the different
      lanthanide counterions. Reduced osmotic pressure curves and Flory-Huggins pair
      interaction parameters have been calculated; both of them were used to estimate
      degrees of dissociation at zero as well as at finite concentrations. Degrees of
      dissociation are decreasing with increasing concentration or vinyl sulfate
      content of the copolymer. They take values between 8-36% at zero polymer
      concentration and they reach zero value simultaneously at approximately 1 x 10(
      3) mol of polymer chains/kg of water. The average number of released counterions
      per polymer chain (DPn = 1005) approaches to a limit of about 4.4 with increasing
      vinyl sulfate content. This corresponds to average charge distances of b > or =
      19 nm and charge density parameters of xi < or = 0.037. The latter is, however, a
      very low value and indicates a 1/9 contraction compared to the rod-like
      assumption.

PMID- 17439275
TI  - Influence of changes in water properties on reactivity in strongly acidic
      microemulsions.
AB  - Replacing the counterion in sodium bis(2-ethylhexyl)sulfosuccinate (NaOT, usually
      known as AOT or Aerosol OT) with H+ (HOT) allows strongly acidic microemulsions
      to be obtained through the effect of a change in the solvation mechanism of the
      surfactant, where the Na+...OH2 interaction is displaced by a stronger H+...OH2
      interaction. This raises the proportion of water bound to the counterion, which
      is reflected in the FT-IR spectrum for water trapped in the microemulsion and the
      1H NMR spectrum for the hydrogen atoms in the water molecules. In NaOT
      microemulsions, the resonance signal for hydrogen atoms in the water molecules
      increases from delta approximately 3.9 ppm at W = 2 (with W = [H2O]/[NaOT]) to
      delta approximately 4.8 ppm at W = 50. In HOT microemulsions, the disparate
      strength of Na+...OH2 and H+...OH2 interactions results in a decrease in the
      resonance signal for the hydrogen atoms in the water molecules from delta
      approximately 8.6 ppm at W = 2 to delta approximately 4.9 ppm at W = 50. These
      changes in the physical properties of water alter chemical reactivity in a way
      that is clearly apparent in solvolytic processes in NaOT and HOT microemulsions.
      Thus, the rate constants of reactions involving an associative mechanism increase
      with decreasing W in NaOT microemulsions, but decrease with decreasing W in HOT
      microemulsions. The disparate behavior is a result of a decreased nucleophilicity
      of interfacial water in HOT microemulsions relative to NaOT microemulsions. For a
      dissociative process the rate constants are greater in HOT microemulsions than in
      NaOT ones, and increase with increasing W in both types of microemulsions, which
      can be ascribed to an increased electrophilicity of interfacial water in HOT
      microemulsions.

PMID- 17439276
TI  - Effect of pressure on the selectivity for the esterification of ethylene glycol
      with propionic acid in supercritical CO2.
AB  - The esterification of ethylene glycol with propionic acid was investigated in
      supercritical CO2 at 50.0 degrees C. The effect of pressure on equilibrium
      conversion and selectivity of ethylene glycol monopropionate (monoester) and
      ethylene glycol dipropinonate (diester) was studied systematically. It was shown
      that the equilibrium conversion and selectivity was nearly independent of
      pressure as pressure was lower than 9 MPa. At higher pressure, however, the yield
      and selectivity of the diester increased considerably, while those of the
      monoester decreased with increasing pressure. The main reason was that reactants
      and products distributed between the vapor phase and liquid phase at higher
      pressures. The solvent power of CO2 for the diester is stronger than that for the
      monoester. More diester molecules in the liquid phase were extracted into the
      vapor at higher pressures, which shifted equilibrium of the consecutive
      reversible reactions.

PMID- 17439277
TI  - Photoinduced electron transfer between the cationic complexes Ru(NH3)5pz2+ and
      trans-RuCl([15]aneN4)NO2+ mediated by phosphate ion: visible light generation of
      nitric oxide for biological targets.
AB  - The photochemical behavior of the tetraazamacrocyclic complex trans
      RuCl([15]ane)(NO)2+ (RuNO2+) in a 10 mM phosphate buffer solution, pH 7.4, and in
      the presence of Ru(NH3)5pz2+ (Rupz2+) is reported. Irradiation (436 nm) of an
      aqueous solution containing both cationic complexes as PF6- salts labilizes NO
      from RuNO2+ with a quantum yield (phiNO) dependent on the concentration of Rupz2+
      with a maximum value of phiNO (1.03(11)x10(-3) einstein mol-1) found for a
      solution with equimolar concentrations (5x10(-5) M) of the two complexes in
      phosphate buffer solution. The quantitative behavior of this system suggests that
      the two cations undergo preassociation such that photoexcitation of the visible
      absorbing Rupz2+ is followed by electron or energy transfer to RuNO2+, which does
      not absorb appreciably at the excitation wavelength, and this leads to NO release
      from the reduced nitrosyl complex. Notably, the NO release was not seen in the
      absence of phosphate buffer; thus, it appears that phosphate ions mediate NO
      generation, perhaps by facilitating formation of a supramolecular complex between
      the two ruthenium cations. Reexamination of the cyclic voltammetry of Rupz2+
      showed that the electrochemical behavior of this species is also affected by the
      presence of the phosphate buffer.

PMID- 17439278
TI  - pH-dependent phase behavior of carbohydrate-based gemini surfactants. The effects
      of carbohydrate stereochemistry, head group hydrophilicity, and nature of the
      spacer.
AB  - The pH-dependent phase behavior and hydroxide-ion adsorption ability of a series
      of (reduced) carbohydrate-based gemini surfactants were studied between pH 2 and
      12. Static and dynamic light scattering were employed to address transitions in
      the aggregate morphologies and cryo-electron microscopy was used to provide
      further evidence for the morphologies present in solution. Changes in aggregate
      structure as a result of a change in solution pH and an accompanying change in
      protonation state or a change in molecular structure can be rationalized in terms
      of the variations in the packing parameter. In this paper we have focused our
      attention on the size of the carbohydrate moiety, the carbohydrate
      stereochemistry and the nature of the spacer (hydrophobic vs hydrophilic). At
      near neutral pH, most of the gemini surfactants form vesicles. Upon lowering of
      the pH, the vesicles undergo a transition toward wormlike micelles followed by a
      transition to spherical micelles. Upon increasing the solution pH, flocculation
      occurs due to charge neutralization followed at still higher pH by redispersion
      and charge reversal of the vesicles through the specific adsorption of hydroxide
      ions to the vesicular surface. Upon decreasing head group size at constant, but
      low, degrees of protonation, the packing parameter has a tendency to become
      larger than one resulting in the formation of inverted phases. Upon further
      decrease in the head group size, oil droplets are observed. In case of a
      hydrophobic spacer, the carbohydrate stereochemistry affects the pH of the
      transitions, but not the type of the transitions. By contrast, for a hydrophilic
      spacer, the pH of the transitions remains unaffected. Adsorption of hydroxide
      ions at basic pH follows similar trends, but was only found for vesicles and oil
      droplets. The large range of structural variations that we have examined allows a
      better understanding of the requirements for the phase transitions for
      carbohydrate-based gemini surfactants as well as for the physisorption of
      hydroxide ions to interfaces in general.

PMID- 17439280
TI  - ChemGPS-NP: tuned for navigation in biologically relevant chemical space.
AB  - Natural compounds are evolutionary selected and prevalidated by Nature,
      displaying a unique chemical diversity and a corresponding diversity of
      biological activities. These features make them highly interesting for studies of
      chemical biology, and in the pharmaceutical industry for development of new
      leads. Of utmost importance, for the discovery of new biologically active
      compounds, is the identification and charting of the corresponding biologically
      relevant chemical space. The primary key to this is the coverage of the natural
      products' chemical space. Here we introduce ChemGPS-NP, a new tool tuned for
      handling the chemical diversity encountered in natural products research, in
      contrast to previous tools focused on the much more restricted drug-like chemical
      space. The aim is to provide a framework for making compound classification and
      comparison more efficient and stringent, to identify volumes of chemical space
      related to particular biological activities, and to track changes in chemical
      properties due to, for example, evolutionary traits and modifications in
      biosynthesis. Physical-chemical properties not directly discernible from
      structural data can be discovered, making selection more efficient and increasing
      the probability of hit generation when screening natural compounds and analogues.

PMID- 17439279
TI  - Effects of backbone and side chain on the molecular environments of chiral
      cavities in polysaccharide-based biopolymers.
AB  - The effects of the backbone and side chain on the molecular environments in the
      chiral cavities of three commercially important polysaccharide-based chiral
      sorbents--cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC), amylose tris(3,5
      dimethylphenylcarbamate) (ADMPC), and amylose tris[(S)-alpha
      methylbenzylcarbamate] (ASMBC)--are studied by attenuated total reflection
      infrared spectroscopy (ATR-IR), X-ray diffraction (XRD), 13C cross
      polarization/magic-angle spinning (CP/MAS) and MAS solid-state NMR, and density
      functional theory (DFT) modeling. These sorbents are used widely in preparative
      scale chiral separations. ATR-IR is used to determine how the H-bonding states of
      the C=O and NH groups of the polymer depend on the backbone and side chain. The
      changes in the polymer crystallinity are characterized with XRD. The changes in
      the polymer helicity and molecular mobility for polymer-coated silica beads
      (commercially called Chiralcel OD, Chirapak AD, and Chiralpak AS) are probed with
      13C CP/MAS and MAS solid-state NMR. The IR wavenumbers and the NMR chemical
      shifts for the polymer backbone monomers and dimers and the side chains are
      predicted at the DFT/B3LYP/6-311+g(d,p) level of theory. It is concluded that the
      molecular environments of the C=O, NH, and phenyl groups show significant
      differences in intramolecular and intermolecular interactions and in the
      nanostructures of the chiral cavities of these biopolymers. These results have
      implications for understanding how the molecular environments of chiral cavities
      of these polymers affect their molecular recognition mechanisms.

PMID- 17439281
TI  - Methylation of sydnone N-oxides: kinetic and thermodynamic control in the
      alkylation site of an electron-rich heterocycle.
AB  - Methylation of the anionic 4-methylcarboxy 1,2,3-oxadiazolate 3-oxide occurs at
      either the disubstituted ring nitrogen or the oxygen of the N-oxide depending
      upon the conditions and reagents employed. Alkylation with methyl iodide leads to
      N-alkylation, while dimethyl sulfate gives O-alkylation and
      trifluoromethanemethylsulfonate gives a mixture of the two products. The
      regioselectivity of these methylations has been confirmed by X-ray diffraction of
      the two products, and these are in turn correlated with their theoretically
      predicted (B3LYP//6-311++G**) relative energies and vibrational spectra.
      Theoretically, N-alkylation is expected to give an isomer that is over 10 kcal
      mol-1 more stable than the O-alkylated product. As a neat melt the kinetic O
      alkylation product cleanly isomerizes in 2 h when heated to 140 degrees C to give
      the thermodynamic N-methylated isomer. Taken together the results illustrate the
      remarkable new sydnone N-oxide derivatives which are readily accessed in this
      chemistry, with the N-alkylation of the sydnone N-oxide, corresponding to the
      first case of such an N-alkylation for a diazenium diolate.

PMID- 17439282
TI  - Oxidation of 2'-deoxycytidine to four interconverting diastereomers of N1
      carbamoyl-4,5-dihydroxy-2-oxoimidazolidine nucleosides.
AB  - Modification of 2'-deoxycytidine (dCyd) by hydroxyl radicals and direct
      ionization leads to the formation of various oxidation products, including dCyd
      5,6-glycols, 5-hydroxy-2'-deoxycytidine, and ring fragmentation products. The
      mechanism of oxidation is complex and poorly understood. In the present work, we
      have prepared four cis- and trans-diastereomers of N1-(2-deoxy-beta-D-erythro
      pentofuranosyl)-1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine by bromination of
      dCyd followed by peroxidation of the resulting dCyd bromohydrins. The structure
      and stereochemistry of each product were determined by 1H NMR, 13C NMR, and 2D
      NOE analyses. The formation of imidazolidine products involves rearrangement of
      initial 5(6)-hydroxy-6(5)-hydroperoxides to C6-C2 endoperoxides, which
      subsequently decompose by a concerted pathway to imidazolidine products. A
      remarkable feature of the four diastereomers was their ability to interconvert
      via single and successive cycles of ring-chain tautomerism at N1-C5 and N3-C4,
      leading to epimerization of C5 and C4, respectively. The rate of isomerization
      was greater for cis-diastereomers compared to trans-diastereomers, and the rate
      sharply increased with pH (pH 9.0>7.0>5.5).

PMID- 17439283
TI  - Efficient synthesis of beta-D-mannosides and beta-D-talosides by double parallel
      or double serial inversion.
AB  - A neighboring equatorial ester group plays a highly important role in the
      Lattrell-Dax (nitrite-mediated) carbohydrate epimerization reaction, inducing the
      formation of inversion compounds in good yields. On the basis of this effect,
      efficient synthetic routes to beta-D-mannosides and beta-D-talosides, from the
      corresponding beta-D-galactosides and beta-D-glucosides, have been designed. The
      present routes are based on multiple regioselective acylation via the respective
      stannylene intermediates, followed by inversions to the corresponding manno- and
      talopyranoside structures by nitrite or acetate substitution. It was found that
      the ester group was able to induce the inversion of its two neighboring groups in
      high yields following either a double parallel or a double serial inversion
      process. By combination of direct inversion, and neighboring- as well as remote
      group participation, several beta-d-mannoside and beta-D-taloside derivatives
      were very conveniently obtained in good yields.

PMID- 17439284
TI  - Control of surface functionality in poly(phenylenevinylene) dendritic
      architectures.
AB  - The efficient synthesis of new asymmetric poly(phenylenevinylene) dendritic
      macromolecules using a stepwise convergent-growth approach is described. By an
      iterative methodology that made use of the Horner-Wadsworth-Emmons (HWE)
      reaction, dendrons and dendrimers up to the third generation, with eight
      different functional groups located at the periphery, were prepared in good
      yields. Both the number and placement of functionalities can be accurately
      controlled to afford a large variety of dendritic architectures.

PMID- 17439286
TI  - Optimizing biomimetic gelators constructed from amino acid building blocks.
AB  - This paper reports the use of a range of amino acids to construct diverse
      gelators, employing structures in which Boc-protected amino acids are attached to
      either end of an aliphatic diamine spacer chain. The choice of amino acid
      determines whether nanoscale self-assembly takes place and controls the
      properties of the resultant material, while the function of the amino acid (e.g.,
      the optical properties of tryptophan) is translated into the self-assembled
      nanostructured gel.

PMID- 17439285
TI  - Double dearomatization of bis(diphenylphosphinamides) through anionic
      cyclization. A facile route of accessing multifunctional systems with antitumor
      properties.
AB  - The sequential one-pot double dearomatization of bis(N-benzyl-P,P
      diphenylphosphinamides) via anionic cyclization is described for the first time.
      Protonation and alkylation of the dearomatized dianions provide bis(tetrahydro
      2,1-benzazaphospholes) in good yield and with very high regio- and stereocontrol.
      Acid-catalyzed methanolysis of the bisheterocycles affords bis(methyl gamma
      aminophosphinates) stereospecifically. The doubly phosphorylated systems proved
      to be active against a series of cancer cell lines.

PMID- 17439287
TI  - Pyrazolo[1,5-a]pyrimidines. Identification of the privileged structure and
      combinatorial synthesis of 3-(hetero)arylpyrazolo[1,5-a]pyrimidine-6
      carboxamides.
AB  - The pyrazolo[1,5-a]pyrimidine class of compounds has been identified as a
      privileged structure for library synthesis on the basis of several key
      characteristics of the core molecule. A chemical set in excess of 400 compounds
      was synthesized to give 3,6,7-substituted pyrazolo[1,5-a]pyrimidinecarboxamides
      9. To facilitate the rapid preparation of this library, a preparative strategy
      included the synthesis of activated p-nitrophenyl esters, followed by subsequent
      scavenging of the p-nitrophenol leaving group. Excess reagents were also removed
      using scavenging reagents that were found to be compatible with the synthetic
      methodology and that afforded target compounds in acceptable purity and yields.

PMID- 17439288
TI  - Low-energy electron transmission through thin-film molecular and biomolecular
      solids.

PMID- 17439289
TI  - Natural products with maleic anhydride structure: nonadrides, tautomycin,
      chaetomellic anhydride, and other compounds.

PMID- 17439290
TI  - Understanding odd-even effects in organic self-assembled monolayers.

PMID- 17439291
TI  - Submicrometer in-plane integrated surface plasmon cavities.
AB  - The optical properties of in-plane integrated surface plasmon polariton (SPP)
      cavities comprised of a thin film area sandwiched between two one-dimensional
      Bragg SPP mirrors are investigated numerically and experimentally. We discuss the
      resonance condition of these cavities, and we analyze in details the physical
      origin of the dispersion of this resonance. On the basis of numerical results, we
      show that in-plane SPP cavities can be used to achieve local SPP field
      enhancement and antireflecting SPP layers. The numerical results are compared to
      near-field optical images recorded by operating a photon scanning tunneling
      microscope. From the near-field images recorded over cavities with different
      sizes at different frequencies, we verify the resonance condition obtained
      numerically and we measure the quality factor of a submicrometer in-plane
      integrated SPP cavity.

PMID- 17439292
TI  - Reducing medical costs and improving quality via self-management tools.

PMID- 17439293
TI  - Rotavirus infection: a systemic illness?

PMID- 17439294
TI  - Rotavirus antigenemia in children is associated with viremia.
AB  - BACKGROUND: Antigenemia is commonly detected in rotavirus-infected children.
      Although rotavirus RNA has been detected in serum, definitive proof of rotavirus
      viremia has not been shown. We aimed to analyze a defined patient population to
      determine if infectious virus could be detected in sera from children with
      rotavirus antigenemia. METHODS AND FINDINGS: Serum samples obtained upon
      hospitalization from children with gastroenteritis (57 stool rotavirus-positive
      and 41 rotavirus-negative), children with diagnosed bronchiolitis of known (n =
      58) or unknown (n = 17) viral etiology, children with noninfectious, nonchronic
      conditions (n = 17), and healthy adults (n = 28) were tested for rotavirus
      antigen by enzyme immunoassay (EIA). Results of serum antigen testing were
      assessed for association with clinical and immunological attributes of the
      children. Rotavirus antigenemia was detected in 90% (51/57) of children with
      rotavirus-positive stools, in 89% (8/9) of children without diarrhea but with
      rotavirus-positive stools, in 12% (2/17) of children with bronchiolitis of
      unknown etiology without gastroenteritis, and in 12% (5/41) of children with
      gastroenteritis but with rotavirus-negative stools. Antigenemia was not detected
      in sera from children with noninfectious nonchronic conditions, children with
      bronchiolitis of known etiology and no gastroenteritis, or healthy adults.
      Neither age nor timing of serum collection within eight days after onset of
      gastroenteritis significantly affected levels of antigenemia, and there was no
      correlation between antigenemia and viral genotype. However, there was a negative
      correlation between serum rotavirus antigen and acute rotavirus-specific serum
      IgA (r = -0.44, p = 0.025) and IgG (r = -0.40, p = 0.01) titers. We examined 11
      antigen-positive and nine antigen-negative sera for infectious virus after three
      blind serial passages in HT-29 cells using immunofluorescence staining for
      rotavirus structural and nonstructural proteins. Infectious virus was detected in
      11/11 (100%) sera from serum antigen-positive children and in two out of nine
      (22%) sera samples from antigen-negative children (p = 0.002). CONCLUSIONS: Most
      children infected with rotavirus are viremic. The presence of viremia is directly
      related to the detection of antigenemia and is independent of the presence of
      diarrhea. Antigenemia load is inversely related to the titer of antirotavirus
      antibody in the serum. The finding of infectious rotavirus in the blood suggests
      extraintestinal involvement in rotavirus pathogenesis; however, the impact of
      rotavirus viremia on clinical manifestations of infection is unknown.

PMID- 17439295
TI  - Medicines without doctors: why the Global Fund must fund salaries of health
      workers to expand AIDS treatment.

PMID- 17439296
TI  - Antibody to aquaporin 4 in the diagnosis of neuromyelitis optica.
AB  - BACKGROUND: Neuromyelitis optica (NMO) is a demyelinating disease of the central
      nervous system (CNS) of putative autoimmune aetiology. Early discrimination
      between multiple sclerosis (MS) and NMO is important, as optimum treatment for
      both diseases may differ considerably. Recently, using indirect
      immunofluorescence analysis, a new serum autoantibody (NMO-IgG) has been detected
      in NMO patients. The binding sites of this autoantibody were reported to
      colocalize with aquaporin 4 (AQP4) water channels. Thus we hypothesized that AQP4
      antibodies in fact characterize NMO patients. METHODS AND FINDINGS: Based on
      these observations we cloned human water channel AQP4, expressed the protein in a
      eukaryotic transcription/translation system, and employed the recombinant AQP4 to
      establish a new radioimmunoprecipitation assay (RIPA). Indeed, application of
      this RIPA showed that antibodies against AQP4 exist in the majority of patients
      with NMO (n = 37; 21 positive) as well as in patients with isolated
      longitudinally extensive transverse myelitis (n = 6; six positive), corresponding
      to a sensitivity of 62.8% and a specificity of 98.3%. By contrast, AQP4
      antibodies were virtually absent in 291 other participants, which included
      patients with MS (n = 144; four positive), patients with other inflammatory and
      noninflammatory neurological diseases (n = 73; one positive), patients with
      systemic autoimmune diseases (n = 45; 0 positive), and healthy participants (n =
      29; 0 positive). CONCLUSIONS: In the largest series reported so far to our
      knowledge, we quantified AQP4 antibodies in patients with NMO versus various
      other diseases, and showed that the aquaporin 4 water channel is a target antigen
      in a majority of patients with NMO. The newly developed assay represents a highly
      specific, observer-independent, and easily reproducible detection method
      facilitating clinically relevant discrimination between NMO, MS, and other
      inflammatory diseases.

PMID- 17439298
TI  - An incentive solution to the peer review problem.

PMID- 17439297
TI  - Law, responsibility, and the brain.

PMID- 17439299
TI  - Does medicine without evolution make sense?

PMID- 17439300
TI  - The genetics of brain wiring: from molecule to mind.

PMID- 17439301
TI  - High incidence of non-random template strand segregation and asymmetric fate
      determination in dividing stem cells and their progeny.
AB  - Decades ago, the "immortal strand hypothesis" was proposed as a means by which
      stem cells might limit acquiring mutations that could give rise to cancer, while
      continuing to proliferate for the life of an organism. Originally based on
      observations in embryonic cells, and later studied in terms of stem cell self
      renewal, this hypothesis has remained largely unaccepted because of few
      additional reports, the rarity of the cells displaying template strand
      segregation, and alternative interpretations of experiments involving single
      labels or different types of labels to follow template strands. Using sequential
      pulses of halogenated thymidine analogs (bromodeoxyuridine [BrdU],
      chlorodeoxyuridine [CldU], and iododeoxyuridine [IdU]), and analyzing stem cell
      progeny during induced regeneration in vivo, we observed extraordinarily high
      frequencies of segregation of older and younger template strands during a period
      of proliferative expansion of muscle stem cells. Furthermore, template strand co
      segregation was strongly associated with asymmetric cell divisions yielding
      daughters with divergent fates. Daughter cells inheriting the older templates
      retained the more immature phenotype, whereas daughters inheriting the newer
      templates acquired a more differentiated phenotype. These data provide compelling
      evidence of template strand co-segregation based on template age and associated
      with cell fate determination, suggest that template strand age is monitored
      during stem cell lineage progression, and raise important caveats for the
      interpretation of label-retaining cells.

PMID- 17439302
TI  - Peptides encoded by short ORFs control development and define a new eukaryotic
      gene family.
AB  - Despite recent advances in developmental biology, and the sequencing and
      annotation of genomes, key questions regarding the organisation of cells into
      embryos remain. One possibility is that uncharacterised genes having nonstandard
      coding arrangements and functions could provide some of the answers. Here we
      present the characterisation of tarsal-less (tal), a new type of noncanonical
      gene that had been previously classified as a putative noncoding RNA. We show
      that tal controls gene expression and tissue folding in Drosophila, thus acting
      as a link between patterning and morphogenesis. tal function is mediated by
      several 33-nucleotide-long open reading frames (ORFs), which are translated into
      11-amino-acid-long peptides. These are the shortest functional ORFs described to
      date, and therefore tal defines two novel paradigms in eukaryotic coding genes:
      the existence of short, unprocessed peptides with key biological functions, and
      their arrangement in polycistronic messengers. Our discovery of tal-related short
      ORFs in other species defines an ancient and noncanonical gene family in
      metazoans that represents a new class of eukaryotic genes. Our results open a new
      avenue for the annotation and functional analysis of genes and sequenced genomes,
      in which thousands of short ORFs are still uncharacterised.

PMID- 17439303
TI  - From parasite to mutualist: rapid evolution of Wolbachia in natural populations
      of Drosophila.
AB  - Wolbachia are maternally inherited bacteria that commonly spread through host
      populations by causing cytoplasmic incompatibility, often expressed as reduced
      egg hatch when uninfected females mate with infected males. Infected females are
      frequently less fecund as a consequence of Wolbachia infection. However, theory
      predicts that because of maternal transmission, these "parasites" will tend to
      evolve towards a more mutualistic association with their hosts. Drosophila
      simulans in California provided the classic case of a Wolbachia infection
      spreading in nature. Cytoplasmic incompatibility allowed the infection to spread
      through individual populations within a few years and from southern to northern
      California (more than 700 km) within a decade, despite reducing the fecundity of
      infected females by 15%-20% under laboratory conditions. Here we show that the
      Wolbachia in California D. simulans have changed over the last 20 y so that
      infected females now exhibit an average 10% fecundity advantage over uninfected
      females in the laboratory. Our data suggest smaller but qualitatively similar
      changes in relative fecundity in nature and demonstrate that fecundity-increasing
      Wolbachia variants are currently polymorphic in natural populations.

PMID- 17439304
TI  - The failure of environmental education (and how we can fix it).

PMID- 17439306
TI  - [Access to oncological drugs in Europe: the discussion generated by the
      "Karolinska Report"].

PMID- 17439307
TI  - [Knowledge management as a key element in improvements to health organisations].

PMID- 17439305
TI  - Whole-genome analysis of histone H3 lysine 27 trimethylation in Arabidopsis.
AB  - Trimethylation of histone H3 lysine 27 (H3K27me3) plays critical roles in
      regulating animal development, and in several cases, H3K27me3 is also required
      for the proper expression of developmentally important genes in plants. However,
      the extent to which H3K27me3 regulates plant genes on a genome-wide scale remains
      unknown. In addition, it is not clear whether the establishment and spreading of
      H3K27me3 occur through the same mechanisms in plants and animals. We identified
      regions containing H3K27me3 in the genome of the flowering plant Arabidopsis
      thaliana using a high-density whole-genome tiling microarray. The results suggest
      that H3K27me3 is a major silencing mechanism in plants that regulates an
      unexpectedly large number of genes in Arabidopsis (~4,400), and that the
      maintenance of H3K27me3 is largely independent of other epigenetic pathways, such
      as DNA methylation or RNA interference. Unlike in animals, where H3K27m3 occupies
      large genomic regions, in Arabidopsis, we found that H3K27m3 domains were largely
      restricted to the transcribed regions of single genes. Furthermore, unlike in
      animals systems, H3K27m3 domains were not preferentially associated with low
      nucleosome density regions. The results suggest that different mechanisms may
      underlie the establishment and spreading of H3K27me3 in plants and animals.

PMID- 17439308
TI  - [A meta-analysis of the effectiveness of aromatase inhibitors as adjuvant
      treatment for postmenopausal patients with breast cancer].
AB  - OBJECTIVE: To evaluate the efficacy and safety of aromatase inhibitors (AIs) as
      adjuvant hormonal therapy for postmenopausal patients with hormone receptor
      positive breast cancer compared with tamoxifen therapy, or as a subsequential
      treatment to this therapy. METHOD: We carried out a bibliographical search using
      the Medline database and papers presented at the American Society of Clinical
      Oncology and the San Antonio Breast Cancer Symposium conferences. The efficacy
      parameters evaluated were disease-free survival (DFS) and overall survival (OS),
      measured after the follow-up period for each of the tests analysed. The data
      selected were subjected to a stratified meta-analysis according to the different
      strategies used to introduce the AIs. The Mantel-Haenszel odds ratio (MH OR; at
      95% CI) was calculated for each of the parameters evaluated. The principal side
      effects with respect to toxicity, described in the various comparative clinical
      trials, have been listed in a table. RESULTS: Compared to tamoxifen, AIs have
      been shown to increase DFS both as a first-line therapy (MH OR = 0.83; 95% CI:
      0.76-0.92) and when sequentially administered for 2-3 years following 2-3 years
      of tamoxifen treatment (MH OR = 0.65; 95% CI: 0.57-0.75). Similarly, their use
      after 5 years of tamoxifen therapy also produces an increase in DFS (MH OR =
      0.63; 95% CI: 0.51-0.77). As for OS, a statistically significant difference is
      obtained only when the AI is administered following 2-3 years of tamoxifen
      treatment (MH OR = 0.77; 95% CI: 0.64-0.94). In comparison with tamoxifen, AIs
      reduce the incidence of thromboembolic and gynaecologic events, although they
      increase bone toxicity. CONCLUSIONS: The clinical studies evaluated show the
      consistent benefits of AIs at different adjuvant treatment stages; however, we
      have been unable to establish the optimum moment for their introduction due to
      the absence of direct comparisons between the different strategies. We now need
      to focus on the selection of patient sub-groups which could benefit from their
      use as a first-line therapy, the long-term toxicity of AIs, and their capacity to
      increase OS, regardless of the strategy followed, after a longer monitoring
      period. In light of the evidence available, bearing in mind certain limitations,
      we propose criteria for the use of AIs in daily clinical practice.

PMID- 17439309
TI  - [The application of new technologies to hospital pharmacy in Spain].
AB  - OBJECTIVE: To describe the degree of introduction of new technologies in the
      medication use process in pharmacy services in Spain. METHOD: A descriptive study
      via a survey into the degree of introduction of computer systems for: management,
      computerized physician order entry (CPOE), automated unit dose drug dispensing,
      preparation of parenteral nutrition solutions, recording drug administration,
      pharmaceutical care and foreseen improvements. The survey was sent by electronic
      mail to the heads of the pharmacy services of 207 hospitals throughout Spain.
      RESULTS: Response index: 82 hospitals (38.6%). 29 hospitals (36.7%) have a
      modular management system, 24 (30.4%) an integrated one and 34 (44.9%) a modular
      integrated one. CPOE is utilised in 17 (22.4%). According to the size of the
      hospital, between 17.9 and 26.7% of unit dose dispensing is done online with a
      management software; between 5.1 and 33.3% of unit dose dispensing is automated.
      Automation of unit dose dispensing centred in the pharmacy service varies between
      10 and 33.3%. Between 13.2 and 35.7% of automated in-ward dispensing systems are
      utilised. Administration records are kept manually on a computerised sheet at 23
      (31.5%) of the hospitals; at 4 (5.4%) on CPOE and 7 (9.5%) online on the integral
      management programme and 4 (5.4%) on specific nursing softwares. Sixty-three per
      cent foresee the implementation of improvements in the short to medium term.
      CONCLUSIONS: The introduction of new technologies is being developed in Spain
      aiming to improve the safety and management of drugs, and there is a trend
      towards increasing their deployment in the near future. It is hoped that their
      fomentation could help to bring about process reengineering within pharmacy
      services in order to increase the time available for devotion to pharmaceutical
      care.

PMID- 17439310
TI  - [The influence of antiretroviral-resistance tests on treatment effectiveness in
      patients with HIV and virological failure].
AB  - OBJECTIVE: The objective of this study is to determine the influence of
      antiretroviral-resistance tests on the suppression of HIV (< 400 copies/mL) in
      patients with virological failure who require an alternative antiretroviral
      treatment. METHOD: A retrospective observational study on cohorts of adult
      patients. Two groups were defined: cases in which the prescription of
      antiretrovirals was based on resistance tests (group A), and controls in which no
      such test was performed (group B). Each group was divided into two sub-groups
      according to the number of changes in treatment: first treatment change (A1 and
      B1); a subsequent change (A2 and B2). The main variable was defined as the
      proportion of patients with negative viral load (< 400 copies/mL) at the third
      month of treatment; secondary variables were the proportion of patients with
      negative viral load at the sixth month and an average variation in the CD4 level
      at the third and sixth months after this change. RESULTS: A total of 152 patients
      were included in this study, 59 in group A and 93 in group B (control). No
      differences were found in the stage of the disease at the time of administering
      an alternative treatment. 59.3% of the patients in group A and 47.3% of the
      patients in group B had suppressed the HIV viral load at the third month,
      although this difference was not statistically significant (p = 0.149). No
      statistically significant differences were found in the secondary variables.
      CONCLUSIONS: The use of antiretroviral-resistance tests increased effectiveness
      in the response to the selected antiretroviral treatment in the study group,
      although we did not obtain significant differences for the group of patients in
      which these tests were not performed.

PMID- 17439311
TI  - [The prophylaxis against post-liver-transplant hepatitis B re-infection].
AB  - OBJECTIVE: To review the prophylaxis against post-liver transplantation hepatitis
      B reinfection with anti-hepatitis B immunoglobulin and nucleoside analogues.
      METHOD: A bibliographic search was carried out using Pubmed, entering the
      following key words: hepatitis B and liver transplantation and (hepatitis B
      hyperimmune globulin and lamivudine and adefovir dipivoxil) up to June 2006. The
      initial search was filtered using the terms clinical trial, randomized clinical
      trial and review. The data contained in selected studies were reviewed. RESULTS:
      A total of 53 works were found. Prophylaxis with anti-HB immunoglobulin and
      lamivudine is the best strategy for avoiding recurrence of the hepatitis B virus
      in patients undergoing hepatic transplants; achieving very low reinfection rates
      (0-10%) with follow up periods of between 1-5 years. There is a great degree of
      variability (dose, duration and method of HBIg administration) in the
      prophylactic protocols reviewed. The use of low doses of anti-HB immunoglobulin
      (administered intravenously followed by intramuscular administration, or
      administered intramuscularly from the anhepatic stage), and lamivudine in
      patients who receive transplants with a low risk of recurrence, shows
      prophylactic efficacy comparable to the use of high doses of anti-HB
      immunoglobulin. Furthermore, it implies a considerable reduction in costs.
      CONCLUSIONS: The availability of suitably designed clinical trials is required to
      design a more cost-effective protocol and reduce variability.

PMID- 17439312
TI  - [Optimising the quality of the unit dose dispensing process through the
      implementation of the semi-automated Kardex system].
AB  - OBJECTIVE: To evaluate the effect of the incorporation of the semi-automated
      Kardex medication storage and dispensing system on the quality of the filling
      process of medicine trolleys in unit doses. METHOD: The speed of filling medicine
      trolleys in unit doses using the Kardex system was analysed retrospectively (n =
      33,946 dispensings) and compared with the manual filling system (n = 5,284
      dispensings); different filling procedures were used and compared. For each
      filling system and procedure, we obtained information for the number of
      dispensings and the time spent carrying this out. The speed of the process was
      calculated as the number of dispensings per hour. In addition, the drugs
      contained in the Kardex system were checked and the correspondence between both
      the actual and the theoretical content was assessed. RESULTS: The speed of the
      trolley filling process, expressed as the number of dispensings per hour,
      increased from 394 with the manual system (filling trolleys individually, n =
      5,284 dispensings) to 417, 540 and 592 with the Kardex system when trolleys were
      filled individually (n = 16,530 dispensings), or grouped in two (n = 10,369
      dispensings) or in three (n = 7,047 dispensings) respectively, at the start of
      the filling process. The check of the contents in the Kardex system detected 36%
      of trays with differences in quantity, one tray with out of date medication and
      three trays which should in theory have been empty and contained medication.
      CONCLUSIONS: The Kardex system optimises the speed of trolley filling with regard
      to the manual system, provided that the trolleys are grouped at the time of
      starting the preparation. The check of the cabinet contents shows that
      possibilities of error exist, related to its handling, which can be minimised by
      incorporating bar codes into the system s replenishment process.

PMID- 17439314
TI  - [Continuous training in pharmacotherapy for specialists in hospital pharmacy].

PMID- 17439313
TI  - [Treatment of vancomycin-resistant Enterococcus with linezolid in paediatric
      hospitals].
AB  - OBJECTIVE: To describe the use of linezolid in vancomycin-resistant Enterococcus
      infections in a paediatric hospital. METHOD: Retrospective, observational study
      of hospitalised patients at the "Juan P. Garrahan" paediatric hospital receiving
      linezolid for the treatment of vancomycin-resistant Enterococcus, during the
      period between January 2002 and July 2004. RESULTS: During 18 months, linezolid
      was prescribed 17 times for a total of 15 seriously ill patients. The median age
      was 7 years old (range: 1 month-15 years) and the median length of the treatment
      was 15 days, with an average hospital stay of 74 days. Infection with vancomycin
      resistant Enterococcus was microbiologically documented in 11 (73.3%) patients;
      they all responded to treatment with linezolid with the exception of two, who
      died while receiving treatment. The most frequently reported adverse reactions
      were of a haematological nature (55.5%). CONCLUSIONS: Linezolid was effective and
      moderately well tolerated for the treatment of vancomycin-resistant Enterococcus
      in children with life-threatening infections.

PMID- 17439315
TI  - [Treatment costs for metastatic colorectal cancer].

PMID- 17439316
TI  - Food consumption, cytochrome P450 3A4 (CYP3A4) presystemic inhibitors, and
      bioavailability of saquinavir.

PMID- 17439317
TI  - [Efalizumab-induced aseptic meningitis].

PMID- 17439318
TI  - [Metformin-induced acute lactic acidosis].

PMID- 17439319
TI  - Electrophoretic separations of cerebrospinal fluid proteins in clinical
      investigations.
AB  - The cerebrospinal fluid (CSF) is a key sample in the research for novel molecular
      biomarkers of neurodegenerative disorders. CSF represents a repertoire of neuro
      secreted, biosynthesised and metabolised molecular products of the central
      nervous system (CNS). Diffusion of macromolecules from the peripheral circulatory
      system to the CSF is highly regulated by the blood-brain barrier, which prevents
      uncontrolled distribution of proteins in the CNS. The development of reproducible
      high resolution separations of proteins in 2-D electrophoresis methods by the
      advent of immobilised pH gradient has opened the route to multivariate holistic
      protein pattern investigation of CSF into neurodegenerative disorders. Moreover,
      the introduction of pre-fractionation techniques such as free flow
      electrophoresis is currently increasing the dynamic depth of proteome analysis.
      Alzheimer's disease (AD) and other forms of dementia, demyelinating diseases,
      Parkinson's disease (PD), and Creutzfeldt-Jakob disease (CJD) have been evaluated
      for biomarker discovery by CSF investigation in multiple studies. However, the
      statistical design of these clinical cross-sectional investigations remains a
      limited factor given the strong statistical power required for complex
      multivariate analysis. These initial evidences are of particular interest in
      dissecting specific molecular mechanisms. The development of fast and economic
      profiling of CSF by linear matrix assisted laser desorption ionisation time-of
      flight mass spectrometry (MALDI-TOF-MS) is providing a new ancillary technology
      to assess sample quality and pre-analytical requirements. In the following we
      take into account all these issues in the CSF proteomics investigation,
      especially highlighting the possible application in the development of clinical
      molecular biomarkers.

PMID- 17439320
TI  - Haemophilia A: molecular insights.
AB  - Haemophilia A is the most common inherited bleeding disorder caused by defects in
      the F8C gene that encodes coagulation factor VIII. This X-linked recessive
      disorder occurs in approximately 1:5000 males. Haemophilia A is diagnosed based
      on normal prothrombin time, altered activated partial thromboplastin time and
      reduced factor VIII activity in plasma. Carrier females are usually asymptomatic
      and can be identified only by molecular analysis. The most frequent mutations in
      F8C are intron 22 and 1 inversions, which occur in approximately 50% and 5% of
      patients, respectively, with a severe phenotype. Large gene deletions are
      observed in approximately 5% of alleles from patients with severe haemophilia A.
      The remaining severe cases and all moderate and mild cases result from numerous
      point mutations and small insertions/deletions, which are de novo mutations in
      one-third of cases. Thus, molecular diagnosis of carrier status and prenatal
      diagnosis in families without intron 22 or 1 inversions is based on scanning
      techniques or gene sequencing. When the disease-causing mutation cannot be
      identified, molecular diagnosis is performed by linkage analysis of several DNA
      polymorphic markers linked to F8C. Given the clinical heterogeneity among
      haemophilic patients, many groups, including our own, have examined the
      relationships between prothrombotic gene variants and haemophilic phenotype to
      investigate whether prothrombotic gene variants modify clinical expression of the
      disease.

PMID- 17439321
TI  - Quality specifications: self pleasure for clinical laboratories or added value
      for patient management?
AB  - Analytical quality specifications play a key role in assuring and continuously
      improving high-quality laboratory services. However, I believe, that there are
      two "missing links" in the effective management of quality specifications in the
      delivery of laboratory services. The first is the evidence that pre-analytical
      variation and related problems are not taken into great consideration by
      laboratory professionals. The second missing link is the communication of quality
      specifications to clinicians and other possible stakeholders. If quality
      specifications represent "the level of performance required to facilitate
      clinical decision-making", they cannot be used only for internal quality
      management procedures but must be communicated to facilitate clinical reasoning,
      decision-making and patient management. A consensus should be achieved in the
      scientific community on these issues to assure better utilization of laboratory
      data and, ultimately, improved clinical outcomes.

PMID- 17439322
TI  - A724A polymorphism of sarco(endo)plasmic reticulum Ca2+-ATPase 2 (SERCA2) in
      hypertensive patients.
AB  - BACKGROUND: Impaired function of calcium ion transporter sarco(endo)plasmic
      reticulum Ca2+-ATPase2 (SERCA2), encoded by ATP2A2 gene, was observed in
      hypertension. The aim of this study was to screen for mutations in the ATP2A2
      gene, in hypertensive patients compared to healthy controls. METHODS: The
      frequency of a novel mutation in exon 15 of ATP2A2, coding SERCA2, was studied in
      107 hypertensive patients and a control group of 50 healthy volunteers. 24-h
      ambulatory blood-pressure monitoring (ABPM) was carried out. ATP2A2 genotyping
      was performed by denaturing HPLC and sequencing. RESULTS: In exon 15 of the
      ATP2A2 gene, a novel c.2171G>A polymorphism was identified that does not change
      the amino acid sequence. The frequency of the A allele was significantly higher
      in normotensive controls than in hypertensive patients (p=0.017). GA genotype
      carriers demonstrated a tendency towards lower blood pressure values in the
      doctor's office (p=0.367 systolic, p=0.439 diastolic blood pressure) and measured
      by ABPM. CONCLUSIONS: Our results suggest a protective role of the A724A
      (c.2171G>A) polymorphism of ATP2A2 in subjects without hypertension.

PMID- 17439323
TI  - Associations of common polymorphisms in the thymidylate synthase, reduced folate
      carrier and 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine
      monophosphate cyclohydrolase genes with folate and homocysteine levels and venous
      thrombosis risk.
AB  - BACKGROUND: Folate is important in purine and thymidylate synthesis and, via
      homocysteine remethylation, facilitates S-adenosylmethionine-dependent
      transmethylation. Low folate availability leads to hyperhomocysteinemia, which is
      a risk factor for arterial vascular disease and venous thrombosis. Genetic
      variation in folate-metabolizing genes may affect folate availability and hence
      confer a greater risk of venous thrombosis. METHODS: We genotyped the thymidylate
      synthase (TYMS) 28-bp repeat and 6-bp deletion, and the reduced folate carrier
      (RFC1) 80G>A and AICAR transformylase/inosine monophosphate (IMP) cyclohydrolase
      (ATIC) 346C>G polymorphisms in population-based controls (n=431), and assessed
      their effect on plasma total homocysteine (tHcy), and serum and red blood cell
      (RBC) folate. We investigated the associations between these variants and disease
      risk in a retrospective case-control study on recurrent venous thrombosis (n=173)
      as well. RESULTS: None of the genotypes, alone or in combination, were associated
      with major changes in tHcy. However, the TYMS 28-bp repeat was associated with
      serum and RBC folate levels. We found no evidence that the genetic variants
      studied were associated with recurrent venous thrombosis risk. CONCLUSIONS: The
      TYMS 28-bp repeat and 6-bp deletion, and RFC1 80G>A and ATIC 346C>G polymorphisms
      are not associated with tHcy, but we did observe an association between the TYMS
      28-bp repeat and serum and RBC folate in a general population. None of the
      polymorphisms was associated with recurrent venous thrombosis risk.

PMID- 17439324
TI  - Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2
      (PPARgamma-2) gene is associated with greater insulin sensitivity and decreased
      risk of type 2 diabetes in an Iranian population.
AB  - BACKGROUND: The Pro12Ala polymorphism of the peroxisome proliferator-activated
      receptor-gamma2 (PPARgamma-2) gene has been variably associated with insulin
      resistance, obesity and type 2 diabetes in several populations. However, this
      association has not been studied in Iranian subjects and we hypothesized that
      this variation might be associated with insulin resistance, type 2 diabetes and
      related metabolic traits in this population. METHODS: The Pro12Ala genotypes were
      determined by PCR-restriction fragment length polymorphism in 696 unrelated
      subjects including 412 non-diabetic controls and 284 type 2 diabetic patients.
      RESULTS: The frequency of the Ala allele was 9.4% and 5.9% in controls and type 2
      diabetic subjects, respectively [adjusted odds ratio (OR) 0.457, p=0.005]. The
      Ala allele did not show a significant effect on anthropometric and biochemical
      parameters in the type 2 diabetic group, whereas in non-diabetic subjects,
      carriers of the Ala allele had significantly lower fasting insulin (p=0.007) and
      homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.009) levels
      compared to Pro/Pro subjects. Multivariate logistic regression analysis showed
      that Pro12Ala polymorphism was an independent determinant of type 2 diabetes in
      this population. CONCLUSIONS: Our results for a sample of Iranian type 2 diabetes
      cases and controls provide evidence that the Pro/Ala genotype of the PPARgamma-2
      gene is associated with insulin sensitivity and may also have protective role
      against type 2 diabetes.

PMID- 17439325
TI  - A novel frameshift mutation of the lecithin:cholesterol acyltransferase (LCAT)
      gene associated with renal failure in familial LCAT deficiency.
AB  - BACKGROUND: The lecithin:cholesterol acyltransferase (LCAT) gene is located on
      the long arm of chromosome 16 and encodes a highly conserved enzyme that
      catalyzes the formation of most plasma lipoprotein cholesteryl esters. Two
      autosomal recessive disorders, familial LCAT deficiency (FLD) and fish eye
      disease, are associated with germline LCAT mutations. Patients with FLD and fish
      eye disease frequently present with corneal opacity, anemia and renal failure
      with proteinuria. METHODS: We clinically and biochemically characterized a German
      patient with classical FLD and used molecular genetic analysis to identify a
      novel homozygous LCAT mutation within codon 178. RESULTS: The insertion of
      adenine identified is located in one of the two motifs that resemble sequences
      found in several lipases, and results in a frameshift with a stop codon at
      residue 214. Therefore, the mutation alters a large portion of the LCAT enzyme,
      including both protein regions with putative lipase activity. Clinically, the
      female patient presented with corneal opacity, mild anemia and a slow
      deterioration in kidney function that led to a requirement for hemodialysis until
      she received a renal transplant. CONCLUSIONS: The present data provide additional
      insights into the genotype/phenotype correlations of FLD and thus may improve the
      genetic diagnosis of this interesting inborn error of metabolism.

PMID- 17439326
TI  - The c.-292C>T promoter polymorphism increases reticulocyte-type 15-lipoxygenase-1
      activity and could be atheroprotective.
AB  - BACKGROUND: Reticulocyte-type 15-lipoxygenase-1 (ALOX15) has anti-inflammatory
      and inflammatory effects and is implicated in the development of asthma,
      arthritis and atherosclerosis. Previously, we screened the human ALOX15 gene for
      variations because genetic variability in ALOX15 might influence these diseases.
      We found a C>T substitution at position c.-292 in the ALOX15 promoter that
      created a novel binding site for the transcription factor SPI1 and increased
      ALOX15 mRNA levels in monocytes from c.-292CT heterozygous volunteers. METHODS:
      To test whether the higher mRNA levels led to higher ALOX15 activity, we
      performed an activity assay and measured the arachidonic acid metabolite 15(S)
      hydroxy-eicosatetraenoic acid [15(S)-HETE] by HPLC analysis. To test whether this
      polymorphism was associated with coronary artery disease (CAD), we investigated
      its association in a case-control study involving 498 Caucasians. RESULTS: The c.
      292C>T polymorphism was associated with higher enzyme activity in heterozygous
      carriers. Intriguingly, this polymorphism also showed a tendency to be protective
      against atherosclerosis. CONCLUSIONS: These results suggest that increased ALOX15
      activity may attenuate inflammation, which could be caused by an increase in
      15(S)-HETE and eventually by its metabolites, the lipoxins.

PMID- 17439327
TI  - The genetic polymorphisms of beta3-adrenergic receptor (AR) Trp64Arg and beta2-AR
      Gln27Glu are associated with obesity in Chinese male hypertensive patients.
AB  - BACKGROUND: Genetic polymorphisms of beta3-adrenergic receptor (AR) Trp64Arg and
      beta2-AR Gln27Glu may result in significant change in the functions of these
      receptors. The aims of the present study were to investigate the association
      between Trp64Arg, Arg16Gly and Gln27Glu polymorphisms and the susceptibility to
      obesity and hypertension in a Chinese population. METHODS: A total of 437 Chinese
      subjects including 149 obese hypertensive patients, 139 non-obese essential
      hypertensive patients, and 149 non-obese normotensive healthy controls were
      enrolled in the study. Polymerase chain reaction-restriction fragment length
      polymorphism (PCR-RFLP) and allele-specific (AS)-PCR assays were used to identify
      Trp64Arg, Arg16Gly, and Gln27Glu genotypes. RESULTS: The allele frequencies of
      64Arg and 27Glu in the obese hypertensive group were 0.178 and 0.128,
      respectively. Both were significantly higher than in the non-obese hypertensive
      and the control groups (p<0.05). Further analysis showed that this association
      existed only in male hypertensive patients. CONCLUSIONS: These data reveal that
      frequencies of beta3-AR 64Arg and beta2-AR 27Glu were significantly higher in our
      obese hypertensive patients than in the non-obese hypertensive population and
      healthy controls. beta3-AR Trp64Arg and beta2-AR Gln27Glu genetic polymorphisms
      are associated with obesity in Chinese male hypertensive patients.

PMID- 17439328
TI  - Diagnostic performance of combined specific urinary proteins and urinary flow
      cytometry in urinary tract pathology.
AB  - BACKGROUND: Urinalysis comprises three techniques: urinary flow cytometry, test
      strip analysis and determination of specific urinary proteins. We investigated
      the diagnostic possibilities of combining these methods for a cohort of patients
      with a variety of well-documented urological and nephrological pathology.
      METHODS: Urinary samples from 407 in- and out-patients with nephrological or
      urological pathology were retrospectively included in our study. Test strip
      analysis (URISYS 2400), urinary flow cytometry (UF-100) and urinary protein
      analysis [albumin, total protein, alpha1-microglobulin (A1M), alpha2
      macroglobulin (A2M)] were performed. RESULTS: In discriminating upper and lower
      urinary tract infections, A1M and A1M/log(white blood cells) can be used, whereas
      pathological casts only give poor discrimination. The ratio A2M/log(red blood
      cells; RBC) allows differentiation between cystitis and pyelonephritis, while
      glomerular diseases can be recognised by the log(RBCxurinary total protein).
      Combining A2M and urinary albumin allows the determination of acute prostatitis.
      CONCLUSIONS: Using combined parameters provided by various urinalysis techniques,
      ratios can be proposed with diagnostic value for classifying renal and urological
      conditions. Possible integration in computer-based knowledge systems may offer
      valuable information for clinicians dealing with these pathologies.

PMID- 17439329
TI  - Diagnostic accuracy of the FIDIS multiplex fluorescent microsphere
      immunodetection system for anti-extractable nuclear antigen (ENA) antibodies in
      connective tissue diseases.
AB  - BACKGROUND: Anti-extractable nuclear antigen antibodies (ENA) are markers of
      connective tissue diseases (CTDs). METHODS: We compared FIDIS reagents in the
      multiplex fluorescent microsphere immunodetection system to INNO-LIA and
      immunodiffusion for 174 antinuclear antibody-positive patients, 102 with well
      defined CTDs and 72 disease controls. RESULTS: No significant differences were
      found in sensitivity or specificity between FIDIS and immunodiffusion, or between
      FIDIS and INNO-LIA for all anti-ENA in all CTD patients; nor were any differences
      found for individual anti-ENAs within distinct CTDs. The FIDIS sensitivity was
      41% (anti-SSA) and 17% (anti-SSB) in lupus erythematosus (LE) or primary
      Sjogren's syndrome; 5% (anti-ribosome and anti-Sm) in LE; 17% (anti-RNP) in LE or
      mixed CTD; 21% (anti-Scl70) in systemic sclerosis; and 61% (anti-centromere) in
      limited systemic sclerosis. The specificity reached 88%-100%. Receiver operating
      characteristic curve areas did not differ between FIDIS and INNO-LIA. Agreement
      ranged from 91% (anti-SSB) to 99% (anti-Jo1) between FIDIS and INNO-LIA, and from
      95% (anti-Scl70) to 100% (anti-Sm) between FIDIS and immunodiffusion. Samples
      scored positive with all techniques in 83% (anti-centromere), 70% (anti-RNP), 67%
      (anti-Jo1), 60% (anti-SSA), 40% (anti-SSB), 33% (anti-ribosome), 25% (anti-Sm)
      and 13% (anti-Scl70) of cases. CONCLUSIONS: The diagnostic performance of FIDIS
      anti-ENA reagents is comparable to immunodiffusion and INNO-LIA.

PMID- 17439330
TI  - Fluorimetric quantitation of citalopram and escitalopram in plasma: developing an
      express method to monitor compliance in clinical trials.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) in general, and
      citalopram/escitalopram in particular, are widely used to treat clinical
      depression. However, SSRI bioavailability and non-compliance represent major
      issues, especially in the clinical trials setting. In this context, frequent drug
      level measurements for compliance monitoring would be a desirable tool to improve
      clinical outcomes with SSRIs. However, the liquid chromatography techniques
      available are expensive, requiring excessive sample preparation, and suffer from
      high complexity. We sought to develop a rapid method for the measurement of
      citalopram/escitalopram levels in human plasma by fluorimetry. METHODS: A total
      of 34 frozen human plasma samples were thawed at room temperature and repeatedly
      centrifuged in cellulose to remove aggregates, proteins and solids. Fluorescence
      spectra were measured in the range 270-450 nm with excitation at 240 nm on a
      FluoroMax 3 spectrofluorimeter. Control samples contained known concentrations of
      SSRIs. RESULTS: SSRI absorbance spectra were recorded in the range 230-320 nm.
      The shape of the spectra and the absorbance of citalopram and escitalopram were
      very similar, with UV maximum absorbance at 239 nm. The maximum extinction
      coefficient was epsilon239=15,930 M-1 cm-1 for citalopram and epsilon239=13,630 M
      1 cm-1 for escitalopram. The fluorescence spectra of SSRIs are unique and are
      characterized by the presence of two well-defined conjugated spectra with maxima
      at 300 and 382 nm. CONCLUSIONS: Fluorimetry is very suitable for assessment of
      plasma SSRI levels. This inexpensive and efficient technique can objectively and
      reliably quantify drug levels in biological fluids, thereby directly determining
      the level of patient adherence to the prescribed drug regimen. This method will
      be useful in a broad spectrum of applications, from compliance/bioavailability
      assessments in animal and human experiments to utilization in large-scale
      clinical trials.

PMID- 17439331
TI  - Free serum cortisol: quantification applying equilibrium dialysis or
      ultrafiltration and an automated immunoassay system.
AB  - BACKGROUND: Quantification of bioactive, free serum cortisol concentrations can
      characterize adrenocortical function more appropriately compared to total serum
      cortisol measurement. Ultrafiltration or equilibrium dialysis of serum samples
      allow direct measurement of free serum cortisol concentrations but respective
      methods have poorly been validated so far. The aim of our study was to
      investigate the analytical performance of free serum cortisol measurement
      employing equilibrium dialysis and ultrafiltration. METHODS: Two commercially
      available ultrafiltration devices and self-assembled dialysis cells,
      respectively, were studied. Cortisol was quantified in filtrate or dialysate
      using an automated immunoassay system. Using two serum pools, the inter-assay
      coefficient of variation was determined for the three methods and a method
      comparison was performed. RESULTS: Inter-assay coefficients of variation (n=10)
      between 3.2% and 14.8% were observed in the imprecision study. Method comparison
      demonstrated close agreement between free serum cortisol results obtained by
      ultrafiltration and equilibrium dialysis, respectively (equilibrium
      dialysis=1.2xultrafiltration+3.9 nmol/L; r=0.99; n=35). CONCLUSIONS: Direct
      quantification of free serum cortisol after equilibrium dialysis or
      ultrafiltration of the samples offers acceptable reproducibility and results in
      close agreement can be obtained. Both methods can potentially be introduced into
      a routine laboratory setting.

PMID- 17439332
TI  - Percutaneous coronary intervention-induced variations in systemic parameters of
      inflammation: relationship with the mode of stenting.
AB  - BACKGROUND: During percutaneous coronary intervention, the technique of stent
      implantation (both direct and complementary stenting) is guided using both
      clinical and angiographic features. We assessed potential relationships between
      procedural parameters and angioplasty-induced variations in inflammatory
      parameters in patients treated by these two different techniques. METHODS: A
      total of 85 consecutive patients due to undergo stent implantation were
      prospectively enrolled. Inflammation was assessed in terms of C-reactive protein,
      fibrinogen, erythrocyte sedimentation rate and leukocyte count in samples taken
      before and 24 h after angioplasty. Patients were classified based on whether they
      underwent complementary (n=47) or direct stenting (n=38). RESULTS: Inflammation
      after complementary stenting was related to the duration of inflation (r=0.59;
      p<0.001), whereas inflammation after direct stenting was related to the inflation
      pressure (r=0.61; p=0.007), as assessed by C-reactive protein variation. None of
      the other parameters influenced the inflammatory response. CONCLUSIONS: The
      inflammatory response after stent implantation depends on the mode of stenting.
      We therefore hypothesize that the inflammatory response after stenting might be
      related to the histological composition of the atherosclerotic plaques involved.

PMID- 17439333
TI  - Multicentre physiological reference values for the concentration of creatininium
      in plasma and diagnostic specificity of glomerular filtration rate estimated with
      the MDRD equation.
AB  - BACKGROUND: The National Kidney Disease Education Program recommends that
      clinical laboratories, when asked for an estimation of glomerular filtration rate
      in a patient by means of the "four-variable" Modification of Diet in Renal
      Disease (MDRD) Study equation, also provide the measurement result for
      creatininium concentration in plasma and the appropriate reference interval. On
      the other hand, clinical laboratories seeking accreditation for compliance with
      ISO 15189:2003 need to demonstrate that the physiological reference intervals
      communicated to all users of laboratory services are appropriate for the patient
      population served, and for their measurement systems. METHODS: Ten clinical
      laboratories in different regions of Spain collaborated in identifying reference
      individuals and producing reference values for the concentration of creatininium
      in plasma using RD/Hitachi Modular Analytics analysers, and for the volume rate
      of glomerular filtrate in kidneys (glomerular filtration rate), estimated with
      the "four-variable" MDRD Study equation. All the logistic work was carried out in
      co-operation with the supplier of the reagents and analysers (Roche Diagnostics
      Espana, S.L., Sant Cugat del Valles, Catalonia, Spain). Using all the reference
      values obtained by each laboratory, multicentre reference limits were estimated
      non-parametrically. RESULTS AND CONCLUSIONS: Reference intervals estimated in
      this study for concentrations of plasma creatininium are 52-85 micromol/L for
      women and 64-106 micromol/L for men. The diagnostic specificity of the estimated
      glomerular filtration rate is 99.2% when applied to healthy persons to screen for
      chronic kidney disease.

PMID- 17439334
TI  - Serum levels of ischemia-modified albumin in healthy volunteers after exercise
      induced calf-muscle ischemia.
AB  - BACKGROUND: Ischemia-modified albumin (IMA) is an emerging marker of ischemia. To
      investigate the applicability of IMA for the diagnosis of skeletal muscle
      ischemia, we examined IMA changes as measured by the albumin-cobalt binding test,
      in a group of healthy volunteers after standardized exercise-induced calf muscle
      ischemia. METHODS: A total of 12 healthy volunteers underwent standardized
      exercise on a plantar flexion pedal. Ischemic conditions were achieved by
      inflating a femoral blood pressure cuff at incremental pressures of 0, 60, 90,
      120 and 150 mm Hg. Calf muscle ischemia was identified by synchronous 31P
      magnetic resonance spectroscopy, measuring intracellular concentrations of
      phosphocreatine (PCr) and inorganic phosphate (Pi). In addition, IMA, serum
      albumin, lactate, troponin T (TnT) and N-terminal pro-B-type natriuretic peptide
      (NT-proBNP) were measured at baseline and at 5, 10, 30, 360 and 720 min after
      cuff release. RESULTS: Magnetic resonance spectroscopy showed calf muscle
      ischemia in all participants upon exercise and cuff inflation. Circulating IMA
      concentrations increased significantly after cuff release (p=0.03) and returned
      to baseline within 30 min. While we found a significant negative correlation with
      albumin, there was no association of IMA levels with lactate or intracellular
      levels of PCr or Pi in samples obtained at baseline and post-ischemia. TnT and NT
      proBNP remained within the normal range throughout the observation period in all
      participants. CONCLUSIONS: IMA may represent a clinical marker for skeletal
      muscle ischemia, although its lack of specificity requires careful clinical
      interpretation of data. The short period of IMA elevation after ischemic exercise
      requires standardized conditions for use as a diagnostic tool and hints at IMA
      applicability as a marker of prolonged or chronic ischemia.

PMID- 17439335
TI  - Reference intervals for follicle-stimulating hormone, luteinizing hormone and
      prolactin in children and young adults on the bioMerieux Mini-Vidas system.
AB  - We measured serum follicle-stimulating hormone (FSH), luteinizing hormone (LH)
      and prolactin concentrations on a bioMerieux Mini Vidas system in a pediatric
      population ranging in age from 1 to 19 years. Reference intervals were
      established separately for females and males, with stratification by age group
      and by Tanner's pubertal stage. FSH values were higher in females than in males,
      and were lowest in both sexes of age class 2 (4-8 years), increasing thereafter
      to the upper limit for stage PIV (females) and stage PV (males). LH values showed
      a similar pattern of change: concentrations were lowest for class 1 (1-3 years)
      and class 2 (4-8 years), and highest for stage PII (females) and stage PV
      (males). No significant difference was observed according to gender. Prolactin
      values did not differ markedly according to gender or pubertal status.

PMID- 17439336
TI  - Limits of usual biochemical alcohol markers in cord blood at term: a
      fetal/maternal population-based study.
AB  - BACKGROUND: After maternal alcohol consumption during pregnancy, many neonates
      affected by less apparent forms of fetal alcohol syndrome disorder (FASD) do not
      receive proper diagnosis or treatment. There is thus a need for laboratory
      markers for early detection of alcohol-exposed neonates. The aim of our study was
      to assess the efficiency of the usual alcohol biomarkers measured in cord blood
      to identify alcohol-exposed neonates immediately after birth. METHODS: A 1-year
      study was conducted in the labor wards of the maternity units of the Auvergne,
      Central France at the time of term delivery. The patients answered an anonymous
      self-completion survey concerning alcohol use (Alcohol Use Disorder
      Identification Test; AUDIT) during their pregnancy. Aspartate aminotransferase,
      alanine aminotransferase, and gamma-glutamyltransferase concentrations and the
      percentage of carbohydrate-deficient transferrin were measured in maternal and
      cord blood. RESULTS: We collected 870 maternal-fetal sample pairs. Two cases
      (0.2%) of typical FASD were detected. We report a non-significant correlation
      between maternal and cord blood biomarkers. None of the cord blood biomarkers
      differed significantly between newborns of alcohol-exposed and unexposed mothers.
      CONCLUSIONS: We demonstrate that the usual alcohol biomarkers are not effective
      in cord blood for identifying alcohol-exposed neonates.

PMID- 17439337
TI  - Implementing the Stockholm Conference hierarchy of objective quality criteria in
      a routine laboratory.
AB  - BACKGROUND: Analytical performance of clinical laboratory testing should be
      evaluated against objective quality specifications. The Stockholm Conference
      consensus recommendation states that from a hierarchy of quality models, the
      highest-ranking model should be used. This study reports the performance of a
      routine clinical laboratory using these quality recommendations. Quality
      standards recommended for use in manufacturers' package inserts are also compared
      against the objective criteria. METHODS: Imprecision of 22 analytes was monitored
      by analyzing three levels of commercial quality control (QC) material daily over
      a 6-month period. The performance for each analyte was evaluated against defined
      quality specifications based on biological variation and the National Cholesterol
      Education Panel (NCEP) criteria. RESULTS: Overall, objective quality
      specifications were met by the laboratory for 18/22 (82%) analytes. The
      performance for analytes not meeting the criteria was assessed against quality
      targets based on a model lower in the hierarchy, i.e., interlaboratory
      imprecision data derived from an accredited EQA program. All analytes met these
      quality targets. When quality targets set by the manufacturer were applied to
      biological variation and NCEP criteria, results for only 8/22 (36%) analytes met
      the targets. CONCLUSIONS: Objective quality specifications can be consistently
      achieved in a routine laboratory. The hierarchy model of the Stockholm Conference
      should be promoted for global adoption.

PMID- 17439338
TI  - The diffusion of innovations theory could help laboratorians in research
      translation.

PMID- 17439339
TI  - Detection of CYP2D6 polymorphisms *9, *10, and *41 using ARMS-PCR and their
      allelic frequencies in 400 psychiatric patients.

PMID- 17439340
TI  - Toward standardization of carbohydrate-deficient transferrin (CDT) measurements:
      I. Analyte definition and proposal of a candidate reference method.
AB  - An alcohol-associated change in the serum transferrin glycoform pattern,
      carbohydrate-deficient transferrin (CDT), is used as a biomarker of chronic
      moderate to heavy alcohol consumption. A current limitation in CDT analysis is
      the lack of standardization, which hampers clinical and analytical comparison
      between studies. This situation prompted initiation of a Working Group (WG) on
      CDT Standardization under the auspices of the International Federation of
      Clinical Chemistry and Laboratory Medicine (IFCC). The standardization work aims
      to define and validate the analyte, select a reference method, work out
      procedures for the production of reference materials, and make suggestions for
      the clinical usage of CDT. The first recommendation of the WG is that
      disialotransferrin should be the primary target molecule for CDT measurement and
      the single analyte on which CDT standardization is based. It is further
      recommended that HPLC should be the analytical principle considered as the basis
      of an interim reference method until a suitable mass spectrometric reference
      method is established. In clinical use, CDT should be expressed in a relative
      amount (% CDT), to compensate for variations in the total transferrin
      concentration.

PMID- 17439341
TI  - Measurement of free thyroxine in laboratory medicine--proposal of measurand
      definition.

PMID- 17439342
TI  - Impaired percent alpha variability on continuous electroencephalography is
      associated with thalamic injury and predicts poor long-term outcome after human
      traumatic brain injury.
AB  - Continuous electroencephalography (cEEG) is potentially useful in determining
      prognosis in patients with traumatic brain injuries (TBI). The objective of this
      prospective, observational cohort study was to determine if the percent alpha
      variability (PAV) on cEEG was predictive of outcome following TBI. Injury
      characteristics were indexed to assess whether lesions in specific cerebral loci
      were correlated with PAV and patient recovery. Fifty-three TBI patients were
      studied using cEEG recording and serial neuroimaging. Clinical recovery was
      assessed at regular intervals in hospital and following discharge. The principal
      outcome measures included the mean 3-day PAV score, the 7-day PAV pattern,
      delineation of the anatomical sites of brain injury, and the 6-month clinical
      outcome, as measured by the Glasgow Outcome Scale (GOS). Significant univariate
      (p = 0.030) and multivariate (p = 0.008) relations were identified between PAV
      and GOS scores. PAV offered good discrimination between favorable and unfavorable
      6-month outcomes (AUC 0.76) and, with a cutpoint of 0.20, had a sensitivity of
      87% and negative predictive value of 82%. Multivariate modeling revealed that
      injuries of the thalamus (p = 0.009) and basal ganglia (p = 0.016), and the
      presence of diffuse edema (p = 0.009), were the key anatomical predictors of PAV.
      Brainstem injuries (p = 0.020) and indicators of diffuse cerebral trauma, such as
      deep white matter shearing (p = 0.036) and multiple subcortical lesions (p =
      0.033), were the principal determinants of 6-month recovery. Inclusion of PAV
      enhanced the accuracy of prediction models that encompassed a selective
      combination of clinical and anatomical variables (adjusted R(2) = 0.458, p <
      0.001). The two main results of this study are (1) PAV is a sensitive predictor
      of 6-month clinical outcomes following TBI, and (2) injury to the thalamus is
      related to impaired PAV. PAV appears best utilized as a functional adjunct to
      traditional clinical and anatomical predictors.

PMID- 17439343
TI  - Magnetic resonance imaging of diffuse axonal injury: quantitative assessment of
      white matter lesion volume.
AB  - Diffuse axonal injury (DAI) is a common mechanism of traumatic brain injury (TBI)
      for which there is no well-accepted anatomic measures of injury severity. The
      present study aims to quantitatively assess DAI by measuring white matter lesion
      volume visible in fluid-attenuated inversion recovery (FLAIR) weighted images and
      to determine whether higher lesion volumes are associated with unfavorable
      functional outcome 6 months after injury. Twenty-four patients who experienced
      moderate to severe TBI without extra-axial or major cortical contusions were
      included in this study. Lesion volume was assessed by quantifying areas of
      hyperintensities in the white matter utilizing digitized FLAIR images. Two
      independent raters processed the magnetic resonance (MR) images and determined
      the total DAI volume. Functional outcome was assessed at 6 months after injury
      using the Glasgow Outcome Scale-Extended (GOSE). Interclass correlation analyses
      showed very high interrater reliability for each measure between the two raters
      (Interclass Correlation Coefficient = 0.95, p <or= 0.001). Total DAI volume was
      significantly, although modestly, correlated to GOSE (r = -0.453, p = 0.034).
      White matter lesion volume resulting from DAI can be quantitatively and reliably
      assessed from standard FLAIR-weighted MRIs. Patients with greater DAI volume have
      poorer functional outcomes. These methods may be useful in stratifying injury
      severity and for the assessment of DAI-directed therapies.

PMID- 17439344
TI  - Subcellular stress response after traumatic brain injury.
AB  - Traumatic brain injury (TBI) initiates a complex genetic response that may
      include the expression of organelle specific stress genes. We investigated the
      effects of brain trauma on the expression of a number of stress genes by in situ
      hybridization and Western blot analysis including the endoplasmic reticulum (ER)
      stress gene grp78, ER protein processing enzymes calnexin and protein disulphide
      isomerase (PDI), the mitochondrial stress gene hsp60, and the cytoplasmic stress
      gene hsp70. Male Sprague-Dawley rats were subjected either to sham-surgery or
      moderate (1.8-2.2 atm) parasagittal fluid-percussion (F-P) brain injury followed
      by 30 min of either normoxic or hypoxic (30-40 mm Hg) gas levels. Expression of
      grp78 was increased in the ipsilateral cerebral cortex and dentate gyrus
      beginning 4 h after trauma plus hypoxia. Similarly, mRNA encoding the
      mitochondrial hsp60 was induced in the ipsilateral outer cortical layers at 4-24
      h after TBI plus hypoxia. Calnexin and PDI mRNAs were not significantly altered
      following TBI with or without secondary hypoxia. In contrast, mRNA of the
      cytoplasmic hsp70 was strongly induced at 4 h after brain injury in multiple
      brain regions within the injured hemisphere, and this expression was greatly
      enhanced by secondary hypoxia. Because subcellular stress gene expression may
      reflect where unfolded or damaged proteins are abundant, these findings suggest
      that abnormal proteins are localized mainly in the cytoplasm, and to a lesser
      degree in the ER lumen and mitochondria after brain trauma. Thus, distinct parts
      of the cellular machinery respond to traumatic and metabolic stresses in specific
      ways.

PMID- 17439345
TI  - Pretreatment with the cyclosporin derivative, NIM811, improves the function of
      synaptic mitochondria following spinal cord contusion in rats.
AB  - Trauma to the spinal cord causes a cascade of secondary events, such as
      mitochondrial dysfunction, which disrupts cellular functions and ultimately leads
      to cell death. Cyclosporin A (CsA) is a potent immunosuppressant that promotes
      mitochondrial function by inhibiting mitochondrial permeability transition (mPT).
      Clinical trials examining CsA in traumatic brain injury are currently under-way,
      but CsA is potentially neurotoxic. NIM811 is a non-immunosuppressive CsA
      derivative that inhibits mPT at nanomolar concentrations and with significantly
      less cytotoxicity than CsA. In the present study, we investigated the effects of
      NIM811 treatment on mitochondrial bioenergetics and the production of reactive
      oxygen species following spinal cord injury (SCI) in rats. Rats were pretreated
      with NIM811 or vehicle, and after 15 min the rats received a "mild/moderate"
      spinal cord contusion. After 24 h, the spinal cords were rapidly removed and
      synaptosomal mitochondria were isolated. NIM811 pretreatment significantly
      improved mitochondrial respiratory control ratios, and the maximal electron
      transport capacity of complex I and II, as well as their ATP-producing capacity.
      Consistent with the improvements in mitochondrial function, NIM811 pretreatment
      significantly decreased free radical production in isolated mitochondria. These
      studies are the first to demonstrate the therapeutic potential of CsA derivatives
      in a model of SCI, and support the need for continued investigation of compounds
      like NIM811 as an acute treatment for human SCI.

PMID- 17439346
TI  - Trauma-associated inflammatory response impairs embryonic stem cell survival and
      integration after implantation into injured rat brain.
AB  - Pluripotent embryonic stem cells were shown to survive and differentiate into
      mature neuronal cells after implantation in experimental models of Parkinson
      disease and cerebral ischemia. Embryonic stem cell transplantation has also been
      proposed as a potential therapy for cerebral trauma, characteristic of massive
      loss of multiple cell types due to primary insult and secondary sequelae. Green
      fluorescent protein (GFP)-transfected murine embryonic stem cells were implanted
      into the ipsi or contralateral cortex of male Sprague-Dawley rats 72 h after
      fluid-percussion injury. Animals were sacrificed at day 5 or week 7
      postimplantation. Brain sections were examined using conventional and fluorescent
      double-labelling immunohistochemistry. Five days after implantation, clusters of
      GFP-positive cells undergoing partial differentiation along neuronal pathway,
      were detected at the implantation site. However, after 7 weeks, only a few GFP
      positive cells were found, indicating an extensive loss of stem cells during this
      time period. For the first time, we proved the observed cell loss to be mediated
      via phagocytosis of implanted cells by activated macrophages. Cerebral trauma,
      induced 3 days prior to implantation, has activated the inflammatory potential of
      otherwise immunologically privileged tissue. Subsequent cell implantation was
      accompanied by reactive astrogliosis, activation of microglia, as well as a
      massive invasion of macrophages into transplantation sites even if the grafts
      were placed into contralateral healthy hemispheres, remote from the traumatic
      lesion. Our results demonstrate a significant post-traumatic inflammatory
      response, which impairs survival and integration of implanted stem cells and has
      generally not been taken into account in designs of previous transplantation
      studies.

PMID- 17439347
TI  - Phosphorylation of calcium calmodulin-dependent protein kinase II following
      lateral fluid percussion brain injury in rats.
AB  - Traumatic brain injury (TBI) can dramatically increase levels of intracellular
      calcium ([Ca(2+)](i)). One consequence of increased [Ca(2+)](i) would be altered
      activity and function of calcium-regulated proteins, including calcium-calmodulin
      dependent protein kinase II (CaMKII), which is autophosphorylated on
      Thr(286)(pCaMKII(286)) in the presence of calcium and calmodulin. Therefore, we
      hypothesized that TBI would result in increased levels of pCaMKII(286), and that
      such increases would occur early after injury in brain regions known to be
      damaged following lateral fluid percussion TBI (i.e., hippocampus and cortex). In
      order to test this hypothesis, immunostaining of CaMKII was examined in rat
      hippocampus and cortex after lateral fluid percussion (LFP) injury using an
      antibody directed against pCaMKII(286). LFP injury produced a marked increase in
      pCaMKII(286) immunostaining in the hippocampus and overlying cortex 30 min after
      TBI. The pattern of increased immunostaining was uneven, and unexpectedly absent
      in some hippocampal CA3 pyramidal neurons. This suggests that phosphatase
      activity may also increase following TBI, resulting in dephosphorylation of
      pCaMKII(286) in subpopulations of CA3 pyramidal neurons. Western blotting
      confirmed a rapid increase in levels of pCaMKII(286) at 10 and 30 min after brain
      injury, and that it was transient and no longer significantly elevated when
      examined at 3, 8, and 24 h. These results demonstrate that TBI alters the
      autophosphorylation state of CaMKII, an important neuronal regulator of critical
      cell functions, including enzyme activities, cell structure, gene expression, and
      neuronal plasticity, and provide a molecular mechanism that is likely to
      contribute to cell injury and impaired plasticity after TBI.

PMID- 17439348
TI  - low-level laser therapy applied transcranially to mice following traumatic brain
      injury significantly reduces long-term neurological deficits.
AB  - Low-level laser therapy (LLLT) has been evaluated in this study as a potential
      therapy for traumatic brain injury (TBI). LLLT has been found to modulate various
      biological processes. Following TBI in mice, we assessed the hypothesis that LLLT
      might have a beneficial effect on their neurobehavioral and histological outcome.
      TBI was induced by a weight-drop device, and motor function was assessed 1 h post
      trauma using a neurological severity score (NSS). Mice were then divided into
      three groups of eight mice each: one control group that received a sham LLLT
      procedure and was not irradiated; and two groups that received LLLT at two
      different doses (10 and 20 mW/cm(2) ) transcranially. An 808-nm Ga-As diode laser
      was employed transcranially 4 h post-trauma to illuminate the entire cortex of
      the brain. Motor function was assessed up to 4 weeks, and lesion volume was
      measured. There were no significant changes in NSS at 24 and 48 h between the
      laser-treated and non-treated mice. Yet, from 5 days and up to 28 days, the NSS
      of the laser-treated mice were significantly lower (p < 0.05) than the
      traumatized control mice that were not treated with the laser. The lesion volume
      of the laser treated mice was significantly lower (1.4%) than the non-treated
      group (12.1%). Our data suggest that a non-invasive transcranial application of
      LLLT given 4 h following TBI provides a significant long-term functional
      neurological benefit. Further confirmatory trials are warranted.

PMID- 17439349
TI  - Electromagnetic controlled cortical impact device for precise, graded
      experimental traumatic brain injury.
AB  - Genetically modified mice represent useful tools for traumatic brain injury (TBI)
      research and attractive preclinical models for the development of novel
      therapeutics. Experimental methods that minimize the number of mice needed may
      increase the pace of discovery. With this in mind, we developed and characterized
      a prototype electromagnetic (EM) controlled cortical impact device along with
      refined surgical and behavioral testing techniques. By varying the depth of
      impact between 1.0 and 3.0 mm, we found that the EM device was capable of
      producing a broad range of injury severities. Histologically, 2.0-mm impact depth
      injuries produced by the EM device were similar to 1.0-mm impact depth injuries
      produced by a commercially available pneumatic device. Behaviorally, 2.0-, 2.5-,
      and 3.0-mm impacts impaired hidden platform and probe trial water maze
      performance, whereas 1.5-mm impacts did not. Rotorod and visible platform water
      maze deficits were also found following 2.5- and 3.0-mm impacts. No impairment of
      conditioned fear performance was detected. No differences were found between
      sexes of mice. Inter-operator reliability was very good. Behaviorally, we found
      that we could statistically distinguish between injury depths differing by 0.5 mm
      using 12 mice per group and between injury depths differing by 1.0 mm with 7-8
      mice per group. Thus, the EM impactor and refined surgical and behavioral testing
      techniques may offer a reliable and convenient framework for preclinical TBI
      research involving mice.

PMID- 17439350
TI  - Behavioral, histological, and ex vivo magnetic resonance imaging assessment of
      graded contusion spinal cord injury in mice.
AB  - This study characterized the Infinite Horizon (IH) Impactor for use in mouse
      models of contusion spinal cord injury (SCI), and investigated the feasibility
      and reliability of using magnetic resonance imaging (MRI) as a method to
      accurately measure lesion volume after mouse contusion SCI. Eight-week-old female
      C57Bl/6 mice received a mild (30 kilodyne), moderate (50 kilodyne), or severe (70
      kilodyne) contusion injury at the T9 vertebral level. Uninjured control mice
      received a T9 laminectomy only. Functional recovery was assessed using the Basso,
      Beattie, Bresnahan (BBB) and Basso Mouse Scale (BMS) open-field locomotor rating
      scales. Next, 4% paraformaldehyde-perfused spinal cords were collected between
      the T6 and T12 spinal roots, and stored in phosphate-buffered saline (PBS) at 4
      degrees C until MRI analysis. MRI lesion volumes were determined using T1
      weighted images on a 7-Tesla MRI. Histology was performed on 20-microm polyester
      wax-embedded sections processed from the same spinal cords for stereological
      determination of fibronectin lesion volume and myelin basic protein spared white
      matter volume. Area of spared white matter at the epicenter was also analyzed.
      The results demonstrated that the IH Impactor produced precise, graded contusion
      SCI in mice. Lesion volumes were positively correlated with force of impact, and
      negatively correlated with spared white matter and functional recovery.
      Additionally, similar lesion volumes were detected using fibronectin staining and
      MRI analysis, although MRI may be more sensitive for milder injuries. These
      results give researchers more options in how to analyze spinal cord injuries in
      animal models.

PMID- 17439351
TI  - Delayed transplantation with exogenous neurotrophin administration enhances
      plasticity of corticofugal projections after spinal cord injury.
AB  - Functional deficits following spinal cord injury (SCI) result from a disruption
      of corticofugal projections at the lesion site. Not only direct regeneration of
      the severed axons but also anatomical re-organization of spared corticofugal
      pathways can reestablish connections between the supraspinal and spinal motor
      centers. We have previously shown that delayed transplantation of fetal spinal
      cord tissue and neurotrophin administration by two weeks after SCI supported
      recovery of forelimb function in adult rats. The current study determined whether
      the same intervention enhances plasticity of corticofugal fibers at the midbrain
      and spinal cord level. Anterograde tracing of the left corticorubral fibers
      revealed that the animals with transplants and neurotrophins (BDNF or NT-3)
      increased the extent of the traced fibers crossing to the right red nucleus (RN),
      of which the axons are spared by a right cervical overhemisection lesion. More
      neurons in the left motor cortex were recruited by the treatment to establish
      connections with the right RN. The right corticorubral projections also increased
      the density of midline crossing fibers to the axotomized left RN in response to
      transplants and neurotrophins. Transplants plus NT-3, but not BDNF, significantly
      increased the amount of spared corticospinal fibers in the left dorsolateral
      funiculus at the spinal level both rostral and caudal to the lesion. These
      results suggest that corticofugal projections retain the capacity until at least
      two weeks after injury to undergo extensive reorganization along the entire
      neuraxis in response to transplants and neurotrophins. Targeting anatomical
      plasticity of corticofugal projections may be a promising strategy to enhance
      functional recovery following incomplete SCI.

PMID- 17439352
TI  - Rescue of rat anterior horn neurons after spinal cord injury by retrograde
      transfection of adenovirus vector carrying brain-derived neurotrophic factor
      gene.
AB  - We investigated the efficacy of retrograde gene delivery via the sternomastoid
      muscle of recombinant adenovirus vector (AdV) carrying brain-derived neurotrophic
      factor (BDNF) gene for the rescue of injured rat spinal cord. One hundred-thirty
      five adult Sprague-Dawley rats were used in the study with a standard weight
      compression technique to produce spinal cord injury. AdV-BDNF gene or AdV-beta
      galactosidase (AdV-LacZ) gene was injected into the sternomastoid muscle
      immediately after traumatic C4 segment spinal cord injury. AdV-BDNF was
      successfully appeared in the injured cervical spinal cord following injection
      into the sternomastoid muscle. BDNF expression in the anterior horn neurons of
      the cervical spinal cord reached peak levels at 1-2 weeks; and the expression
      persisted at significant levels for approximately 4 weeks after injury. AdV-BDNF
      transfection was associated with increased numbers of intact neurons as confirmed
      by Nissl, cholineacetyltransferase (ChAT), and acetylcholine esterase (AChE)
      staining especially from 2 weeks after injury, compared with the AdV-LacZ
      injected rats. Our results suggest that in vivo targeted retrograde AdV-BDNF-gene
      delivery may enhance neuronal survival following traumatic injury of the spinal
      cord.

PMID- 17439353
TI  - Active range of motion as an indicator for ligament and membrane lesions in the
      upper cervical spine after a whiplash trauma.
AB  - In the present study, we examined whether active range of neck motion (AROM)
      differed between persons with and without a diagnosis of whiplash-associated
      disorder type 2 (WAD2) and explored whether magnetic resonance (MR)-verified
      lesions of specific ligaments or membranes at the craniovertebral junction was
      associated with increased or decreased motion in any particular direction among
      the WAD2 patients. A CROM goniometer was used for registration of flexion,
      extension, side bending (left and right) and rotation (left and right),
      respectively. The neck structures considered were the alar and the transverse
      ligaments, and the tectorial and the posterior atlanto-occipital membranes. Our
      study comprised 87 WAD2 patients and 29 control persons without any known neck
      injury. For comparing mean values of AROM between the groups, t-test and analysis
      of variance (ANOVA) were used. WAD patients had on average a shorter range of
      active motion for all movements compared with the control group. The difference
      was statistically significant for all measures considered, except side bending to
      the left. Among the WAD patients, increasing severity of lesions to the alar
      ligaments was associated with a decrease in maximal flexion and rotation. A
      similar pattern was seen for lesions to the transverse ligament, but the trend
      test was not significant. An abnormal posterior atlanto-occipital membrane was
      associated with shorter range of left rotation, with a significant trend test
      both in analyses with and without adjustment for lesions to other structures. No
      significant association was found in relation to lesions to the tectorial
      membrane, but very few persons had such lesions. These findings indicate that
      soft tissue lesions may affect neck motion as reflected by AROM. However, since
      lesions to different structures seem to affect the same movement, AROM alone is
      not a sufficient indicator for soft-tissue lesions to specific structure in the
      upper cervical spine.

PMID- 17439354
TI  - CPG15, a new factor upregulated after ischemic brain injury, contributes to
      neuronal network re-establishment after glutamate-induced injury.
AB  - Candidate plasticity-related gene 15 (cpg15) encodes a protein that regulates
      dendritic and axonal arbor growth and synaptic maturation. In the present study,
      we investigated the potential role of CPG15 in regulating the neuronal network re
      establishment after ischemic brain injury. In the mouse model with transient
      global ischemia (TGI), CPG15 transcripts and proteins were determined using RT
      PCR and Western blot analyses. Cell proliferation was observed using 5'-bromo-2'
      deoxyuridine-5'-monophosphate (BrdU) labeling. Double immunostaining and
      depletion of soluble CPG15 proteins were performed to examine the cellular
      distribution of CPG15 and the role of soluble CPG15 in the neurite outgrowth
      during the neuronal network re-establishment in primarily cultured hippocampal
      cells after glutamate-induced injury. We demonstrated that CPG15 expression in
      the hippocampus was upregulated at 1-2 weeks after TGI. In the dentate gyrus, the
      number of CPG15 and BrdU positive cells increased concurrently after the injury.
      During the neuronal network re-establishment after the glutamate-induced injury
      of primarily cultured hippocampal cells, CPG15 was mainly located at the ends and
      turn-off regions of the growth cones and in the vesicles. Depletion of soluble
      CPG15 proteins secreted from the hippocampal cells in the culture media
      significantly reduced the neurite outgrowth and neuron-neuron connection. The
      results indicate that CPG15 may function as a new factor required in re
      establishment of neuronal network after the injury. Our findings will be
      important in developing a new strategy to enhance endogenous neurogenesis after
      an ischemic brain injury.

PMID- 17439355
TI  - NMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain
      barrier permeability changes after experimental subarachnoid hemorrhage in the
      rat.
AB  - Increased levels of glutamate and aspartate have been detected after subarachnoid
      hemorrhage (SAH) that correlate with neurological status. The NMDA receptor
      antagonist felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an anti
      epileptic drug that elicits neuroprotective effects in different experimental
      models of hypoxia-ischemia. The aim of this dose-response study was to evaluate
      the effect of FBM after experimental SAH in rats on (1) behavioral deficits
      (employing a battery of assessment tasks days 1-5 post-injury) and (2) blood
      brain barrier (BBB) permeability changes (quantifying microvascular alterations
      according to the extravasation of protein-bound Evans Blue by a
      spectrophotofluorimetric technique 2 days post-injury). Animals were injected
      with 400 muL of autologous blood into the cisterna magna. Within 5 min, rats
      received daily oral administration of FBM (15, 30, or 45 mg/kg) for 2 or 5 days.
      Results were compared with sham-injured controls treated with oral saline or FBM
      (15, 30, or 45 mg/kg). FBM administration significantly ameliorated SAH-related
      changes in Beam Balance scores on days 1 and 2 and Beam Balance time on days 1-3,
      Beam Walking performance on days 1 and 2, and Body Weight on days 3-5. FBM also
      decreased BBB permeability changes in frontal, temporal, parietal, occipital, and
      cerebellar cortices; subcortical and cerebellar gray matter; and brainstem. This
      study demonstrates that, in terms of behavioral and microvascular effects, FBM is
      beneficial in a dose-dependent manner after experimental SAH in rats. These
      results reinforce the concept that NMDA excitotoxicity is involved in the
      cerebral dysfunction that follows SAH.

PMID- 17439356
TI  - Neurotoxic effects of exogenous recombinant tissue-type plasminogen activator on
      the normal rat brain.
AB  - Thrombolytic therapy with intravenous and intra-arterial recombinant tissue-type
      plasminogen activator (rtPA) has been established for the treatment of acute
      ischemic stroke. However, tPA has also been suggested to have neurotoxic effects.
      The purpose of this study was to examine direct neurotoxicity of rtPA in vivo.
      The animals (Wistar rats) were divided to the following three groups: low-dose
      (15 micromol/L) rtPA group (n = 6); high-dose (30 micromol/L) rtPA group (n = 6);
      and control (physiological saline) group (n = 6). The rtPA solution was perfused
      into the cortex via a microdialysis probe. The volume of the lesion was
      quantified histologically by image analysis of the lesions. Blood-brain barrier
      (BBB) disruption was evaluated by intravenous injection of Evans blue, and injury
      to the basal lamina was evaluated by immunohistochemistry using an anti-laminin
      antibody. In the rtPA-perfused animals, a pale lesion was produced around the
      probe, and microscopically, neurons showed necrotic changes. The volume of the
      lesions increased significantly as the concentration of perfused rtPA was
      increased. Marked extravasation of Evans blue was observed, and laminin
      immunoreactivity of blood vessels in the rtPA-induced lesions was lost. These
      results suggest that rtPA promotes acute direct neurotoxicity and participates in
      disruption of the microvascular basal lamina to cause BBB disruption, thereby
      increasing edema formation.

PMID- 17439357
TI  - Viral interleukin-10 gene transfer prevents liver ischemia-reperfusion injury:
      Toll-like receptor-4 and heme oxygenase-1 signaling in innate and adaptive
      immunity.
AB  - Ischemia-reperfusion injury (IRI) contributes to early and late dysfunction of
      liver transplants. We have shown that sentinel Toll-like receptor-4 (TLR4) plays
      a key role in the activation of T cell immune responses during hepatic IRI. We
      have also documented that overexpression of heme oxygenase-1 (HO-1) exerts potent
      cytoprotective effects. This study analyzes how adenovirus (Ad)-based viral
      interleukin-10 (vIL-10) gene transfer affects TLR4 and HO-1 signaling in host
      innate and adaptive immunity during liver IRI. Using a partial lobar warm IRI
      model, groups of wild-type and HO-1(+/-) knockout (KO) mice were assessed for
      severity of hepatocellular damage after 90 min of warm ischemia followed by 6 hr
      of reperfusion. Both wild-type and HO-1 (+/-) KO mice treated with Ad-vIL-10 have
      shown improved hepatic function (serum glutamic-oxaloacetic transaminase levels),
      ameliorated histological signs of IRI (Suzuki's score), decreased neutrophil
      accumulation (myeloperoxidase activity), and depressed tumor necrosis factor
      alpha/IL-1beta, IL-2/interferon-gamma, E-selectin, and macrophage inflammatory
      protein-2 expression. These effects were IL-10 dependent as treatment with
      neutralizing antibody re-created liver IRI. In contrast, untreated wild-type and
      HO-1 (+/-) KO mice, as well as wild-type and HO-1 (+/-) KO mice treated with Ad
      beta-Gal, showed severe hepatocellular damage due to IRI. Unlike in controls,
      wild-type and HO-1 (+/-) KO mice treated with Ad-vIL-10 revealed markedly
      depressed TLR4 and NF-kappaB expression, along with increased HO-1 and Bcl-2/Bcl
      x(L) expression, as compared with respective controls. Thus, vIL-10 gene transfer
      prevents hepatic IRI in association with depressed expression of innate TLR4, and
      adaptive Th1 cytokine/chemokine programs. The induction of antioxidant HO-1 and
      anti-apoptotic Bcl-2/Bcl-x(L) by vIL-10 exerts synergistic cytoprotective
      function against antigen-independent hepatic inflammatory response triggered by
      IRI.

PMID- 17439358
TI  - Magnetic resonance-compatible robotic and mechatronics systems for image-guided
      interventions and rehabilitation: a review study.
AB  - The continuous technological progress of magnetic resonance imaging (MRI), as
      well as its widespread clinical use as a highly sensitive tool in diagnostics and
      advanced brain research, has brought a high demand for the development of
      magnetic resonance (MR)-compatible robotic/mechatronic systems. Revolutionary
      robots guided by real-time three-dimensional (3-D)-MRI allow reliable and precise
      minimally invasive interventions with relatively short recovery times. Dedicated
      robotic interfaces used in conjunction with fMRI allow neuroscientists to
      investigate the brain mechanisms of manipulation and motor learning, as well as
      to improve rehabilitation therapies. This paper gives an overview of the
      motivation, advantages, technical challenges, and existing prototypes for MR
      compatible robotic/mechatronic devices.

PMID- 17439359
TI  - Nanotechnology applications in cancer.
AB  - Cancer nanotechnology is an interdisciplinary area of research in science,
      engineering, and medicine with broad applications for molecular imaging,
      molecular diagnosis, and targeted therapy. The basic rationale is that nanometer
      sized particles, such as semiconductor quantum dots and iron oxide nanocrystals,
      have optical, magnetic, or structural properties that are not available from
      molecules or bulk solids. When linked with tumor targeting ligands such as
      monoclonal antibodies, peptides, or small molecules, these nanoparticles can be
      used to target tumor antigens (biomarkers) as well as tumor vasculatures with
      high affinity and specificity. In the mesoscopic size range of 5-100 nm diameter,
      nanoparticles also have large surface areas and functional groups for conjugating
      to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and
      therapeutic (e.g., anticancer) agents. Recent advances have led to bioaffinity
      nanoparticle probes for molecular and cellular imaging, targeted nanoparticle
      drugs for cancer therapy, and integrated nanodevices for early cancer detection
      and screening. These developments raise exciting opportunities for personalized
      oncology in which genetic and protein biomarkers are used to diagnose and treat
      cancer based on the molecular profiles of individual patients.

PMID- 17439361
TI  - The last word: books as a statistical metaphor for microbial communities.
AB  - Microbial communities contain unparalleled complexity, making them difficult to
      describe and compare. Characterizing this complexity will contribute to
      understanding the ecological processes that drive microbe-host interactions,
      bioremediation, and biogeochemistry. Moreover, an estimate of species richness
      will provide an indication of the completeness of a community profile. Such
      estimates are difficult, however, because community structure rarely fits a well
      defined distribution. We present a model based on the word usage in books to
      illustrate the power of statistical tools in describing microbial communities and
      suggesting biological hypotheses. The model also generates data to test these
      methods when there are insufficient data in the literature. For example, by
      simulating the word distribution in books, we can predict the number of words
      that must be read to estimate the size of the vocabulary used to write the book.
      Combined with other models that have been used to make inaccessible problems
      tractable, our book model offers a unique approach to the complex problem of
      describing microbial diversity.

PMID- 17439362
TI  - Effects of brain evolution on human nutrition and metabolism.
AB  - The evolution of large human brain size has had important implications for the
      nutritional biology of our species. Large brains are energetically expensive, and
      humans expend a larger proportion of their energy budget on brain metabolism than
      other primates. The high costs of large human brains are supported, in part, by
      our energy- and nutrient-rich diets. Among primates, relative brain size is
      positively correlated with dietary quality, and humans fall at the positive end
      of this relationship. Consistent with an adaptation to a high-quality diet,
      humans have relatively small gastrointestinal tracts. In addition, humans are
      relatively "undermuscled" and "over fat" compared with other primates, features
      that help to offset the high energy demands of our brains. Paleontological
      evidence indicates that rapid brain evolution occurred with the emergence of Homo
      erectus 1.8 million years ago and was associated with important changes in diet,
      body size, and foraging behavior.

PMID- 17439363
TI  - Vitamin E regulatory mechanisms.
AB  - Dietary and supplemental vitamin E is absorbed and delivered to the liver, but of
      the various antioxidants with vitamin E activity, only alpha-tocopherol is
      preferentially recognized by the alpha-tocopherol transfer protein (alpha-TTP)
      and is transferred to plasma, while the other vitamin E forms (e.g., gamma
      tocopherol or tocotrienols) are removed from the circulation. Hepatic alpha-TTP
      is required to maintain plasma and tissue alpha-tocopherol concentrations. The
      liver is the master regulator of the body's vitamin E levels in that it not only
      controls alpha-tocopherol concentrations, but also appears to be the major site
      of vitamin E metabolism and excretion. Vitamin Es are metabolized similarly to
      xenobiotics; they are initially omega-oxidized by cytochrome P450s, undergo
      several rounds of beta-oxidation, and then are conjugated and excreted. As a
      result of these various mechanisms, liver alpha-tocopherol and other vitamin E
      concentrations are closely regulated; thus, any potential adverse vitamin E
      effects are limited.

PMID- 17439365
TI  - Interpreting intelligence test results for children with disabilities: is global
      intelligence relevant?
AB  - School psychological and neuropsychological evaluations typically include
      intellectual and other standardized assessment tools in the identification of
      children with disabilities. The clinical utility of intellectual assessment in
      the identification and treatment of these children has been repeatedly
      challenged, with alternatives such as a response to intervention or global
      intelligence score interpretation offered to replace the long-held tradition of
      idiographic interpretation of intellectual factors or subtests for the purpose of
      differential diagnosis and individualized intervention. Replicating previous
      work, this study examined the structure of intellectual functioning for children
      diagnosed with Learning Disability (LD; n=128), Attention-Deficit/Hyperactivity
      Disorder (ADHD; n=71), and traumatic brain injury (TBI; n=29) using regression
      commonality analysis. Across groups, results provide substantial evidence for a
      multifactorial representation of intellectual functioning for children with LD,
      ADHD, or TBI, with little shared variance among factor predictors of FSIQ in each
      analysis. As global intellectual functioning, represented by the shared variance
      among all predictors, was largely absent and instead composed of several discrete
      elements with the requisite specificity for individual interpretation,
      idiographic interpretation appears to be warranted for children with
      disabilities.

PMID- 17439370
TI  - Validity of WAIS-III performance scale subtests completed with the non-dominant
      hand.
AB  - Many patients with hemiplegia use only the non-dominant hand to complete the WAIS
      III. It is not known to what degree this administrative change alters scores on
      specific subtests. To answer this question, we compared scores on Digit Symbol
      Coding, Block Design, Picture Arrangement, Object Assembly, and Symbol Search via
      standard administration (SA) with scores from non-dominant hand administration
      (NDA). Fifty-eight college students were assigned to either SA or NDA groups.
      There were 29 SAs and 29 NDAs with means for age of 19.48 years (SD=1.15) and
      25.68 years (SD=7.46). Relative to the SA group, the average Digit Symbol-Coding
      and Symbol Search scores were reduced by 4.04 and 1.62 points by NDA. Scores on
      the other subtests were not adversely affected by NDA.

PMID- 17439371
TI  - Neuropsychological sequelae of ethylene glycol intoxication: a case study.
AB  - Ingestion of Ethylene glycol (EG) can result in a clinical syndrome marked by
      renal, cardiopulmonary, and neurological dysfunction. We present a case study
      addressing EG intoxication with neurological, radiological, and
      neuropsychological findings several days to weeks after initial ingestion and
      again at follow-up six months later. In our case study, CT scans of the head on
      days one and two post EG ingestion were essentially normal, as was a brain MRI
      six months later. An MRI of the brain on day five revealed nonspecific cerebellar
      white matter abnormalities. Neuropsychological assessment at three to four weeks
      post admission indicated global cognitive impairment with particular deficits in
      attention, processing speed, constructional ability, language, and memory
      retrieval. Results at six months follow-up indicated partial improvement in
      overall cognitive functioning with remaining deficits in processing speed,
      naming, and constructional ability. These findings suggest that EG intoxication
      is capable of causing lasting neuropsychological sequelae despite evidence of
      relatively normal neuroradiologic findings.

PMID- 17439374
TI  - Toward optimal health: Janine A. Smith, M.D., discusses vision impairment in
      women: interviewed by Jodi Godfrey.

PMID- 17439375
TI  - Jennifer fever in academic medicine.

PMID- 17439376
TI  - Reasons for unprotected intercourse in adult women.
AB  - BACKGROUND: Despite the increased availability of contraception, unprotected
      intercourse and unintended pregnancy are common among adult women. We sought to
      identify reasons why adult women at risk of unintended pregnancy have unprotected
      intercourse. METHODS: A comprehensive search of electronic databases of MEDLINE,
      CINAHL, and PSYCHOINFO, from 1995 to 2005, was conducted. Reference lists from
      relevant published papers and reviews related to contraceptive practices and
      pregnancy intendedness were also hand searched. The Bronfenbrenner ecological
      framework was used as a guide in the discussion of the findings. RESULTS: There
      were 16 studies that met inclusion criteria, and these provided numerous reasons
      why adult women had unprotected intercourse. Reasons were found at the
      individual, interpersonal, and societal levels. Individual reasons included
      concerns with contraceptive side effects, a low perceived risk for pregnancy,
      lack of knowledge, and attitudes and beliefs. Interpersonal reasons included
      partners, families, or friends who discouraged the use of contraception. Societal
      reasons included access problems, inconvenience, and cost. CONCLUSIONS: There are
      multiple reasons why women have unprotected intercourse. These reasons were
      located in overlapping domains of influence. Factors in a woman's environment at
      the interpersonal and societal level may significantly influence her
      contraceptive use behavior.

PMID- 17439377
TI  - Understanding barriers for adherence to follow-up care for abnormal pap tests.
AB  - OBJECTIVE: Approximately 4000 women annually will die from preventable and
      treatable cervical cancer. Failure to adhere to follow-up recommendations after
      an abnormal Pap test can lead to development of cervical cancer. This paper
      summarizes the body of literature on adherence to follow-up after an abnormal Pap
      test in order to facilitate development of interventions to decrease morbidity
      and mortality due to cervical cancer. METHODS: We conducted a comprehensive
      search of published literature addressing risk factors for adherence or
      interventions to improve adherence following an abnormal Pap test as the outcome.
      We included peer-reviewed original research conducted in the United States from
      1990 to 2005. RESULTS: Fourteen analytical and twelve experimental studies that
      met our criteria were reviewed. Lesion severity and health beliefs were
      consistently associated with adherence rates. Communication interventions,
      including telephone reminders, counseling, and educational sessions, increased
      follow-up compliance across intervention studies. Inconsistent evidence for
      associations among race, income, and age were found. CONCLUSIONS: Further
      research is needed to reinforce current studies addressing health beliefs and
      social support. Interventions that focus on the interplay among psychological,
      educational, and communication barriers are necessary. These interventions should
      be adapted and applied across various racial/ethnic and socioeconomic groups to
      reach all women with a high-risk profile for invasive cervical cancer.

PMID- 17439378
TI  - Menopause transition stage and endogenous estradiol and follicle-stimulating
      hormone levels are not related to cognitive performance: cross-sectional results
      from the study of women's health across the nation (SWAN).
AB  - BACKGROUND: By one estimate, 60% of women experiencing the menopause transition
      perceive that they have memory problems, but most studies that have used
      cognitive function tests have not substantiated a relation between menopause
      stage and cognitive performance. We sought to describe the cross-sectional
      relation between menopause status, estradiol (E(2)), follicle-stimulating hormone
      (FSH), and measured cognitive function. METHODS: Cross sectional analysis of a
      community-based cohort of midlife women was used. Cognitive tests were the East
      Boston Memory Test, Symbol Digit Modalities, and Digits Span Backward. Menopause
      categories (premenopausal, early perimenopausal, late perimenopausal, and
      postmenopausal) were defined based on menstrual patterns. One set of general
      linear models assessed the relations between each cognitive test and menopause
      transition category, initially adjusted for age, race/ethnicity, education,
      symptoms, self-rated general health, and body mass index (BMI); next, these were
      additionally adjusted for FSH and E(2). A second set of models, stratified by
      menopause status, examined the possible relations between each cognitive test and
      either E(2) or FSH, adjusted for age, race/ethnicity, education, symptoms, self
      related general health, and BMI. RESULTS: The mean age of the analytical sample
      (n = 1657) was 49.7 years. Only 5% of the sample had less than a high school
      education, 16% graduated from high school, and the rest had at least some
      college. The percent of women in each menopause category was premenopausal
      (9.0%), early perimenopausal (57.0%), late perimenopausal (13.4%), postmenopausal
      (20.6%). Although clinical-site adjusted models showed moderate differences
      between menopause transition groups and cognitive performance, no association was
      found between each of the measured cognitive performance tests and menopause
      transition status when adjusting for covariates. Similarly, no association
      between each cognitive test and E(2) or FSH was found. CONCLUSIONS: This study
      does not support a cross-sectional relation between cognitive test performance
      and menopause stage, FSH, or E(2).

PMID- 17439379
TI  - Glucosamine use in pregnancy: an evaluation of pregnancy outcome.
AB  - BACKGROUND: Glucosamine (GLS) is an endogenous aminomonosaccharide. It is used as
      a disease-modifying agent for the treatment of osteoarthritis. There is no
      information regarding its use in pregnancy. Our objective was to determine
      whether GLS treatment in pregnancy is associated with an increased risk of major
      malformations or other adverse outcomes. METHODS: Pregnant women were recruited
      from The Motherisk Program at the Hospital for Sick Children, Toronto, Canada.
      Women exposed to GLS were compared with women exposed to nonteratogenic agents.
      They were matched for gestational age at time of call, maternal age, and
      cigarette and alcohol consumption. Rates of major malformations and other end
      points of interest were compared between the two groups. RESULTS: We were able to
      ascertain the outcomes of 54 women who used GLS during pregnancy (34 during
      organogenesis). There were 50 live births (two sets of twins), 4 spontaneous
      abortions, 1 therapeutic abortion, and 1 stillbirth, with no major malformations.
      The mean birth weight was 3524 +/- 482 g, and the median gestational age at birth
      was 39 weeks (range 37-40). CONCLUSIONS: These limited data suggest no increased
      risk for major malformations or other adverse fetal effects following the use of
      GLS during pregnancy.

PMID- 17439380
TI  - Financial barriers to mammography: who pays out-of-pocket?
AB  - OBJECTIVE: This study investigates how out-of-pocket payments for mammograms vary
      according to the characteristics of women and the states where they reside.
      METHODS: We conducted a cross-sectional analysis for women >or=40 years using
      data from the 2000 National Health Interview Survey (NHIS) Cancer Control Module
      linked with state characteristics. Descriptive tabulations and logistic
      regressions were used to examine characteristics associated with out-of-pocket
      payment for a woman's most recent mammogram for the subset of approximately 7000
      women reporting a mammogram within the past 2 years. RESULTS: In 2000, the
      majority of women who received a mammogram within the past 2 years paid no out-of
      pocket costs: 68% among those aged 40-64 and 85% among those aged >or=66. Among
      women aged 40-64 with a recent mammogram, characteristics associated with paying
      out-of-pocket for the last mammogram were white, non-Hispanic race/ethnicity,
      being uninsured, having non-HMO private coverage, place of residence outside the
      Northeast, in a non-metropolitan county, and in a state with low HMO penetration.
      CONCLUSIONS: Public insurance and HMO coverage have been especially effective in
      eliminating financial barriers to mammography, but women 40-64 years with public
      coverage still lag behind their privately insured counterparts in using
      mammography. Out-of-pocket costs remain a barrier to use for uninsured women.
      Older women, although less likely than younger women to pay out-of-pocket for
      mammograms, remain less likely to use mammography than younger women.

PMID- 17439382
TI  - Carotid artery intima-media thickness after raloxifene treatment.
AB  - BACKGROUND: Raloxifene, a selective estrogen receptor modulator (SERM), decreases
      total and low-density lipoprotein cholesterol (LDL-C) in postmenopausal women and
      inhibits increases in intima-media thickness (IMT) in animal models. We tested
      whether up to 8 years exposure to raloxifene had an effect on subclinical
      atherosclerosis in the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE)
      trial and the follow-up study, the 4-year Continuing Outcomes Relevant to Evista
      (CORE) trial. METHODS: A subsample of postmenopausal women with osteoporosis, who
      had completed the MORE and CORE trials and were on average 68 years of age and 19
      years postmenopausal at randomization into MORE, participated in this substudy.
      Within 6 months of cessation of study drug in CORE, right common carotid artery
      IMT (CIMT) and carotid artery stiffness and arterial compliance were measured at
      one of two sites (San Diego and San Francisco) using high-resolution B-mode
      ultrasound. CIMT and arterial stiffness measures were compared between women who
      had received raloxifene vs. placebo; the primary analysis included only women who
      were >or=80% drug compliant and had used <or=6 months of lipid-lowering
      medication during CORE. RESULTS: For the primary analysis dataset (n = 89), there
      was no significant difference in mean CIMT between the raloxifene and placebo
      groups (0.83 and 0.81 mm, respectively, p = 0.62). Carotid artery stiffness and
      compliance were not significantly different between treatment groups (p = 0.33
      and 0.59, respectively). CONCLUSIONS: These preliminary data suggest that in this
      self-selected group of elderly post-menopausal women with osteoporosis who were
      evaluated within 6 months of cessation of study medication, there were no
      differences between long-term raloxifene treatment and placebo groups in several
      measures of subclinical atherosclerosis.

PMID- 17439381
TI  - The association between soy nut consumption and decreased menopausal symptoms.
AB  - BACKGROUND: Epidemiological studies suggest a low incidence of hot flashes in
      populations that consume dietary soy. The present study examined the effect of
      soy nuts on hot flashes and menopausal symptoms. METHODS: Sixty healthy
      postmenopausal women were randomized in a crossover design to a therapeutic
      lifestyle changes (TLC) diet alone and a TLC diet of similar energy, fat, and
      protein content in which one-half cup soy nuts divided into three or four
      portions spaced throughout the day (containing 25 g soy protein and 101 mg
      aglycone isoflavones) replaced 25 g of nonsoy protein. During each 8-week diet
      period, subjects recorded the number of hot flashes and amount of exercise daily.
      At the end of each 8-week diet period, subjects filled out the menopausal symptom
      quality of life questionnaire. RESULTS: Compared to the TLC diet alone, the TLC
      diet plus soy nuts was associated with a 45% decrease in hot flashes (7.5 +/- 3.6
      vs. 4.1 +/- 2.6 hot flashes day, respectively, p < 0.001) in women with >4.5 hot
      flashes/day at baseline and 41% in those with <or=4.5 hot flashes/day (2.2 +/-
      1.2 vs. 1.3 +/- 1.1, respectively, p < 0.001). Soy nut intake was also associated
      with significant improvement in scores on the menopausal symptom quality of life
      questionnaire: 19% decrease in vasomotor score (p = 0.004), 12.9% reduction in
      psychosocial score (p = 0.01), 9.7% decrease in physical score (p = 0.045), and a
      trend toward improvement in the sexual score, with a 17.7% reduction in symptoms
      (p = 0.129). The amount of exercise had no effect on hot flash reduction.
      CONCLUSIONS: Substituting soy nuts for nonsoy protein in a TLC diet and consumed
      three or four times throughout the day is associated with a decrease in hot
      flashes and improvement in menopausal symptoms.

PMID- 17439383
TI  - Ethnicity and nutrient intake among Arizona WISEWOMAN participants.
AB  - BACKGROUND: Diet quality and risks of chronic disease have been identified, yet
      nutrient intakes from older uninsured populations have been scarcely described.
      METHODS: Using the dietary intake profiles of an older, uninsured, and mostly
      Hispanic sample of Arizona WISEWOMAN participants, two ethnic groups were
      compared: Mexican American and non-Hispanic white women. Sociodemographic data
      related to nutrient intakes were identified. Estimated mean nutrient intakes of
      Mexican Americans (n = 260) and non-Hispanic white (n = 88) women were compared
      based on ethnicity and acculturation levels. Using linear regression models,
      associations of individual characteristics were made on nutrients for which
      reported intakes were less than the estimated average requirement (EAR). RESULTS:
      Mexican Americans had energy, vitamin E, and niacin intakes that were
      significantly lower than those of non-Hispanic whites, whereas vitamin A intake
      was significantly higher among Mexican Americans. Less acculturated Mexican
      American women had significantly higher intakes of vitamin E and folate than
      their more acculturated counterparts. For both ethnic and acculturation groups,
      intakes of vitamin E, calcium, and potassium were lower than the established
      standards in more than 70% of this population. Having a high body mass index
      (BMI) was associated with lower reported energy intake and higher protein and
      potassium intakes, and smoking was associated with lower intakes of vitamin E and
      folate. CONCLUSIONS: Mexican American women had overall lower micronutrient
      intakes compared with uninsured non-Hispanic white older women; this difference
      may be attributed to their underreporting intake.

PMID- 17439384
TI  - Risk factors for poor self-rated health in women at 2 months and 1 year after
      childbirth.
AB  - OBJECTIVE: To investigate risk factors for poor self-rated health (SRH) in
      primiparous and multiparous women 2 months and 1 year after childbirth in a
      nationwide Swedish sample. METHODS: Women were recruited at their first booking
      visit at 593 (97%) antenatal clinics in Sweden during 3 weeks evenly spread over
      1 year (1999-2000). Data were collected by questionnaires in early pregnancy, 2
      months and 1 year after childbirth, and from the Medical Birth Register. In
      total, 2424 women filled in all the questionnaires, including a global question
      on SRH. The representativity of the sample was assessed by comparison with the
      total Swedish birth cohort of 1999. Data were analyzed by logistic regression
      analysis. RESULTS: Physical problems, such as tiredness, musculoskeletal
      symptoms, and abdominal pain, and emotional problems, such as depressive
      symptoms, increased the risk of poor SRH in both primiparas and multiparas at one
      or both time points. Infant-related risk factors in both groups were negative
      experience of breastfeeding (2 months) and infant sleeping problems (1 year), and
      prematurity was a risk factor in primiparas at 2 months. Insufficient social
      support increased the risk in multiparas. In primiparas, outcome of labor, such
      as negative birth experience after operative delivery, was associated with poor
      SRH at 1 year and perineal pain at 2 months. CONCLUSIONS: A new mother's SRH is
      associated with her life situation. Ongoing physical and emotional problems, lack
      of support, and infant factors seem more important than sociodemographic
      background. Mode of delivery and childbirth experience may have a longterm effect
      on SRH.

PMID- 17439385
TI  - Health hazards in middle-aged women with cardiovascular disease: a case-control
      study of swedish women. the women's health in the Lund area (WHILA) study.
AB  - OBJECTIVE: To delineate the health profile in middle-aged women with
      cardiovascular disease (CVD). METHODS: The Women's Health in the Lund Area
      (WHILA) project covered all women born 1935-1945 (n = 10,766) living in the Lund
      area; 6917 (64.2%) women completed a generic questionnaire and underwent physical
      and laboratory assessments. Of the 6917 women, 6416 were postmenopausal women, of
      whom 104 had CVD. For each woman with CVD, two controls were selected and matched
      for age, smoking habits, body mass index (BMI), waist/hip ratio (WHR), low
      density lipoprotein cholesterol (LDL-C), high-density liproprotein cholesterol
      (HDL-C), diastolic blood pressure and hormonal status. RESULTS: One hundred four
      women (1.6%) reported CVD. Forty-nine had a myocardial infarction (MI), 49 had a
      stroke, and 6 women had both events; 71.4% were postmenopausal, with never use of
      hormone therapy (HT) (PM0), and 28.6% were postmenopausal with ever use of HT
      (PMT). Compared with the control group, serum androstendione was lower (p =
      0.004) in the case group, and menopausal estradiol (E(2)) values were less
      frequent (p = 0.037) in cases from the PM0 group. Among psychological and somatic
      symptoms, nervousness (p < 0.05), difficulty relaxing, crying easily, visual
      disturbance (p </= 0.01 for all), dizziness, difficulties in voiding urine,
      shortness of breath, breast tenderness, and constipation (p </= 0.001 for all)
      were more common among women with CVD. Women with CVD expressed less satisfaction
      with feeling healthy, body image, memory loss, irritability, and sexuality (p </=
      0.05 for all). The case group had more problems with daily activities, more days
      spent in hospital during the previous 5 years, and more regular medical
      appointments with healthcare centers, more often had diabetes mellitus (DM) (p <
      0.001 for all), and had experienced more falls in the previous year (p < 0.05).
      Urinary incontinence and decreased body weight were more common among cases (p
      </= 0.01 for both). CONCLUSION: Several health hazards as well as somatic and
      psychological symptoms were more common in subjects with CVD, rendering them more
      susceptible to future disease.

PMID- 17439386
TI  - The prevalence, burden, and treatment of urinary incontinence among women in a
      managed care plan.
AB  - OBJECTIVE: Urinary incontinence (UI) symptoms are common among women, yet only a
      small proportion of women with incontinence receive a diagnosis and treatment. We
      used survey and utilization data to determine the prevalence, burden, and
      treatment use for incontinence among women at Kaiser Permanente in Northern
      California. METHODS: In 2002, we surveyed 6726 female health plan members about
      health issues, including incontinence. We assessed type and bothersomeness of
      incontinence symptoms in the previous 7 days. For survey respondents and a 10%
      sample of female plan members (n = 108,825), we assessed use from 1997 to 2003.
      RESULTS: The survey response rate was 49.7% (3344 of 6726); 44% of respondents
      reported incontinence symptoms in the previous 7 days, with over half of these
      women reporting that these symptoms bothered them. Fifteen percent of women with
      incontinence symptoms had a diagnosis consistent with incontinence in the
      previous 5 years. One third of the women reporting current bothersome
      incontinence and 14 or more incontinence episodes in the last 7 days had a
      diagnosis consistent with incontinence in the previous 5 years. Among women who
      had received medical or surgical treatment for incontinence in the previous 5
      years, approximately half currently report being bothered by their symptoms.
      CONCLUSIONS: Prevalence of bothersome incontinence symptoms among females in a
      prepaid health plan is high. However, only a small proportion of these women
      received a diagnosis or treatment for incontinence symptoms in the last 5 years.
      Efforts to improve the detection and treatment of bothersome incontinence
      symptoms are needed.

PMID- 17439387
TI  - Perceptions of clinical research participation among African American women.
AB  - BACKGROUND: Recruiting minority women into clinical research remains a
      significant challenge to conducting ethnically representative research. The main
      objective of this Office on Women's Health, DHHS-funded e-health database
      evaluation project was to examine African American women 's thoughts and
      perceptions about the clinical research process and about participation in the
      University of Michigan Women's Health Registry research database. METHODS: Thirty
      one African American women were recruited from the community to participate in a
      total of five 90-minute focus group discussions. All sessions were audiotaped and
      transcribed verbatim. Thematic content analysis was used to identify relevant
      themes about participation in clinical research and the Women's Health Registry.
      RESULTS: Ten common trends were identified. (1) Information about the Women's
      Health Registry is not reaching the community. (2) Research is perceived as
      biased to benefit Caucasians. (3) Community involvement by the research team is
      critical for trust to develop. (4) Research directly relevant to African
      Americans or their community will encourage participation. (5) Researchers should
      use existing networks and advertise in appropriate locations. (6) The community
      needs more information concerning research. (7) Compensation is important. (8)
      Research that addresses a personal or family medical problem encourages
      involvement. (9) Minority representation on the research team is a motivator to
      participation. (10) There is limited time for healthcare-related activities.
      CONCLUSIONS: Successful recruitment strategies for African American women should
      feature community-based, culturally appropriate approaches. Online research
      databases for subject recruitment will likely be successful only if implemented
      within a broader community-oriented program.

PMID- 17439388
TI  - Response to "access to cervical cancer screening: training internists so skill
      limitations are not a barrier to care".

PMID- 17439391
TI  - Genomic and morphological changes of neuroblastoma cells in response to three
      dimensional matrices.
AB  - Advances in neural tissue engineering require a comprehensive understanding of
      neuronal growth in 3 dimensions. This study compared the gene expression of SH
      SY5Y human neuroblastoma cells cultured in 3-dimensional (3D) with those cultured
      in 2-dimensional (2D) environments. Microarray analysis demonstrated that, in
      response to varying matrix geometry, SH-SY5Y cells exhibited differential
      expression of 1,766 genes in collagen I, including those relevant to
      cytoskeleton, extracellular matrix, and neurite outgrowth. Cells extended longer
      neurites in 3D collagen I cultures than in 2D. Real-time reverse transcriptase
      polymerase chain reaction experiments and morphological analysis comparing
      collagen I and Matrigel tested whether the differential growth and gene
      expression reflected influences of culture dimension or culture material. SH-SY5Y
      neuroblastoma cells responded to geometry by differentially regulating cell
      spreading and genes associated with actin in similar patterns for both materials;
      however, neurite outgrowth and the expression of the gene encoding for
      neurofilament varied with the type of material. Electron microscopy and
      mechanical analysis showed that collagen I was more fibrillar than Matrigel, with
      larger inter-fiber distance and higher stiffness. Taken together, these results
      suggest complex cell-material interactions, in which the dimension of the culture
      material influences gene expression and cell spreading and the structural and
      mechanical properties of the culture material influence gene expression and
      neurite outgrowth.

PMID- 17439395
TI  - Design criteria for a modular tissue-engineered construct.
AB  - A modular construct, created by the assembly of discrete microscale objects, has
      been proposed to enable the engineering of large, vascularized tissues containing
      multiple cell types. A simple theoretical analysis of the design constraints
      relevant to a modular construct was performed and used to define useable device
      operating ranges. The analysis assumed that the primary design constraint was the
      operating wall shear stress that would lead to a non-thrombogenic endothelial
      cell layer. At the lower end of the desirable shear range, oxygen depletion (over
      the length of the construct) limited the maximum allowed construct length,
      whereas at the upper end of this shear range, construct pressure difference
      limited maximum construct length. To compare with the theoretical analysis, real
      constructs were assembled, and construct porosity was assessed using superficial
      velocity-pressure difference profiles. Significant deviations from ideal
      construct porosity were observed for soft collagen gel constructs. Improvement of
      the module mechanical properties through the use of poloxamine instead of
      collagen as the module material enabled constructs closer to the ideal case to be
      assembled. With such improvements, modular tissue engineering offers a feasible
      strategy for the development of clinically significant whole-organ replacements.

PMID- 17439396
TI  - Inhibitory effect on replicative DNA polymerases, human cancer cell
      proliferation, and in vivo anti-tumor activity by glycolipids from spinach.
AB  - We succeeded in purifying a major glycolipids fraction (i.e., Fraction-II) in the
      class of monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG)
      and sulfoquinovosyl diacylglycerol (SQDG) from spinach using hydrophobic column
      chromatography. Fraction-II inhibited the activities of replicative DNA
      polymerases (pols) such as alpha, delta and epsilon, and mitochondrial pol gamma
      with IC(50) values of 43-79 microg/ml, but had no influence on the activity of
      repair-related pols beta and lambda. MGDG, DGDG, SQDG were purified from Fraction
      II of spinach using silica gel column chromatography, and SQDG was the strongest
      inhibitor of mammalian pols in the three glycolipids. Therefore, SQDG and its
      related compounds were chemically synthesized, and the sulfate group and fatty
      acid moiety of the compound were suggested to be important for pol inhibition.
      These glycolipids showed no effect even on the activities of plant pols,
      prokaryotic pols and other DNA metabolic enzymes such as T4 polynucleotide
      kinase, T7 RNA polymerase and deoxyribonuclease I. Fraction-II also inhibited the
      proliferation of human cervix carcinoma (HeLa) cells with LD(50) values of 57
      microg/ml, and could halt the cell cycle at the G1-phase, and subsequently
      induced severe apoptosis. In an in vivo anti-tumor assay on nude mice bearing
      solid tumors of HeLa cells, Fraction-II was shown to be a promising suppressor of
      solid tumors. Histopathological examination revealed that tumor necrosis with
      hemorrhage was significantly enhanced with Fraction-II in vivo. The spinach
      Fraction-II containing SQDG might be a potent anti-tumor compound, and may be a
      healthy food substance with anti-tumor activity.

PMID- 17439397
TI  - Targeting cell cycle kinases for cancer therapy.
AB  - Many tumor-associated mutations result in the abnormal regulation of protein
      kinases involved in the progression throughout the cell division cycle. The
      cyclin-dependent kinase (CDK) family has received special attention due to their
      function as sensors of the mitogenic signals and their central role in cell
      proliferation. These kinases are frequently upregulated in human cancer most
      frequently due to overexpression of their cyclin partners or inactivation of the
      CDK inhibitors. A plethora of small-molecule CDK inhibitors have been
      characterized in the last years and some of them are currently under clinical
      development. Other serine-threonine protein kinases such as the Aurora proteins
      (mostly Aurora A and B) or Polo-like kinases (PLK1) are receiving increased
      attention as putative cancer targets. Other less studied mitotic kinases such TTK
      (MPS1), BUB and NEK proteins might also be relevant candidates as new targets of
      interest in cancer therapy since they play relevant roles on mitotic progression
      and the spindle checkpoint. Although targeting cell cycle kinases is an efficient
      procedure to arrest cell proliferation, the best strategy to potently and
      specifically inhibit tumor cell proliferation is not obvious yet. Thus, some cell
      cycle kinases may be of interest as targets to abrogate checkpoints and favor
      apoptotic cell death in tumor cells. New biochemical and genetic studies are
      required to clarify the use of these kinases as targets in new opportunities to
      improve cancer therapy.

PMID- 17439398
TI  - Mass spectrometric profiling of low-molecular-weight volatile compounds-
      diagnostic potential and latest applications.
AB  - The theoretical use of mass spectrometric profiling of low-molecular-weight
      volatile compounds, as one possible method to non-invasively and rapidly diagnose
      a variety of diseases, such as cancer, infection, and metabolic disorders has
      greatly raised the profile of this technique over the last ten years. Despite a
      number of promising results, this technique has not been introduced into common
      clinical practice yet. The use of mass spectrometric profiling of exhaled air is
      particularly hampered by various technical problems and basic methodological
      issues which have only been partially overcome. However, breath analysis aside,
      recently published studies reveal completely new ideas and concepts on how to
      establish fast and reliable diagnosis by using this valuable tool. These studies
      focussed on the headspace screening of various bodily fluids and sample fluids
      obtained during diagnostic procedures, as well as microbial cell cultures and
      demonstrated the vast diagnostic potential of this technique in a wide variety of
      settings, predominantly in vitro. It is the aim of the present review to discuss
      the most commonly detected low-molecular-weight volatile compounds and to
      summarize the current potential applications, latest developments and future
      perspectives of this promising diagnostic approach.

PMID- 17439399
TI  - Porphycenes: facts and prospects in photodynamic therapy of cancer.
AB  - The photodynamic process induces cell damage and death by the combined effect of
      a photosensitizer (PS), visible light, and molecular oxygen, which generate
      singlet oxygen ((1)O(2)) and other reactive oxygen species that are responsible
      for cytotoxicity. The most important application of this process with increasing
      biomedical interest is the photodynamic therapy (PDT) of cancer. In addition to
      hematoporphyrin-based drugs, 2nd generation PSs with better photochemical
      properties are now studied using cell cultures, experimental tumors and clinical
      trials. Porphycene is a structural isomer of porphyrin and constitutes an
      interesting new class of PS. Porphycene derivatives show higher absorption than
      porphyrins in the red spectral region (lambda > 600 nm, epsilon > 50000 M-(1)cm(
      1)) owing to the lower molecular symmetry. Photophysical and photobiological
      properties of porphycenes make them excellent candidates as PSs, showing fast
      uptake and diverse subcellular localizations (mainly membranous organelles).
      Several tetraalkylporphycenes and the tetraphenyl derivative (TPPo) induce
      photodamage and cell death in vitro. Photodynamic treatments of cultured tumor
      cells with TPPo and its palladium(II) complex induce cytoskeletal changes,
      mitotic blockage, and dose-dependent apoptotic or necrotic cell death. Some
      pharmacokinetic and phototherapeutic studies on experimental tumors after
      intravenous or topical application of lipophilic alkyl-substituted porphycene
      derivatives are known. Taking into account all these features, porphycene PSs
      should be very useful for PDT of cancer and other biomedical applications.

PMID- 17439400
TI  - Chemical events behind leukoaraiosis: medicinal chemistry offers new insight into
      a specific microcirculation disturbance in the brain (a chemical approach to a
      frequent cerebral phenotype).
AB  - Leukoaraiosis (LA), one of the most frequent causes of cognitive disturbances, is
      presumed to involve vascular demyelinization and cerebral small-vessel diseases.
      Although it has been suggested that the development of LA is associated with
      cerebral circulatory disturbances, the pathomechanism of this circulatory problem
      is not completely understood. Extensive debate is continuing as regards the
      detailed features of the circulatory disturbances in LA. An endothelial
      dysfunction may lead to breakdown of the blood-brain barrier, thereby resulting
      in chronic toxic edema in the perivascular areas. This can then cause the slow
      development of LA. Endothelial dysfunctions may also give rise to molecular
      events involving a shift in the O(2) and CO(2) trafficking system in the red
      blood cells, which will result in special complex microcirculation disturbances
      in the white matter of the brain; these molecular phenomena may therefore account
      for chronic slight hypoxia leading to the development of LA. This article
      discusses these hypothetical alternative molecular events behind LA. The review
      also illustrates how medicinal chemistry can offer new insight into a common, but
      still mysterious cerebral phenotype.

PMID- 17439401
TI  - Biomarkers in COPD.
AB  - Chronic Obstructive Pulmonary Disease is characterized by an abnormal
      inflammatory response of the lungs to noxious particles and gases, caused
      primarily by cigarette smoking. Although COPD affects the lung, it also produces
      significant systemic consequences. Inflammation, proteases-antiproteases
      imbalance, oxidative stress, tissue damage and tissue repair, apoptosis and
      several genes seem to be involved in the pathogenesis of the disease. The
      cellular and molecular events underlying COPD pathogenesis are driven by
      multifunctional molecules including enzymes, cytokines, chemokines, growth
      factors, lipid mediators and their respective receptors. A large number of
      biomarkers evaluated in COPD, showed a high degree of redundancy. Nevertheless,
      current understanding of the pathobiology of COPD suggests a number of biomarkers
      as potential candidates. The development of relevant markers of lung damage,
      pulmonary inflammation, and systemic disease will be essential to our further
      understanding of the natural history of COPD and the discovery of new, effective
      treatments for its progression. This review summarizes recent findings, on
      potential pulmonary biomarkers in the induced sputum, the exhaled air condensate,
      the peripheral blood, the urine, the bronchoalveolar lavage fluid, and in
      selective cases, in bronchial biopsies.

PMID- 17439402
TI  - Evaluation and management of severe asthma.
AB  - Severe and difficult-to-treat asthma patients have impaired health status and
      account for over half of the cost of the disease and probably all of its
      mortality. Guideline-based treatment for these refractory asthma patients
      includes high doses of inhaled steroids and long acting beta2-agonists (LABA) as
      well as additional medication such as theophylline, oral steroids and leukotriene
      antagonists. However, management regimens are rarely successful in these
      patients, the treating physicians are often at a loss and there are still many
      areas of uncertainty regarding steroid-responsiveness, safety issues and maximal
      dosing of inhaled corticosteroids (ICS) and bronchodilators and possible
      differences between ICS preparations. Furthermore, there are many other classes
      of medication that have been or are currently tested in severe asthma: Anti -
      Immunoglobulin E (IgE) seems to have a good clinical effect while results on anti
      - Interleukin 5 (IL-5) are less promising and anti - tumor necrosis factor alpha
      (TNFalpha) treatment is currently being tested in controlled studies. Other
      steroid sparing drugs (cyclosporine, tacrolimus, methotrexate, gold) have been
      used but results are unsatisfactory and side-effects are notable so steroids
      remain the cornerstone of severe asthma treatment. The addition of macrolides is
      beneficial in many cases and this is in step with the evidence of chronic
      chlamydia infection in severe asthma. Although there are case reports supporting
      the use of Immunoglobulin G (IgG), there are no controlled studies supporting
      this type of treatment. In this report, the authors review the various issues of
      guideline based therapy but also new approaches that include anti-IgE antibodies,
      anti-cytokines (anti-IL-5, anti-IL9, anti-TNF).

PMID- 17439403
TI  - Polycomb protein Cbx4 promotes SUMO modification of de novo DNA methyltransferase
      Dnmt3a.
AB  - The 'de novo methyltransferase' Dnmt3a (DNA methyltransferase 3a) has been shown
      to mediate transcriptional repression. Post-translational modification of Dnmt3a
      by SUMOylation affects its ability to transcriptionally repress. However, very
      little is known about how the SUMOylation process is regulated. In the present
      study, we identified a PcG (Polycomb group) protein, Cbx4 (chromobox 4), as a
      specific interaction partner of Dnmt3a. Co-expression of Cbx4 and SUMO-1 (small
      ubiquitin-related modifier-1) along with Dnmt3a in transfected cells results in
      enhanced modification of Dnmt3a with SUMO-1. Purified Cbx4 also promotes
      SUMOylation of Dnmt3a in vitro. The modification occurs in the N-terminal
      regulatory region, including the PWWP (Pro-Trp-Trp-Pro) domain. Our results
      suggest that Cbx4 functions as a SUMO E3 ligase for Dnmt3a and it might be
      involved in the functional regulation of DNA methyltransferases by promoting
      their SUMO modification.

PMID- 17439404
TI  - Firing of transcription and compartmentalization of splicing factors in tomato
      radicle nuclei during germination(1).
AB  - BACKGROUND INFORMATION: Germination is a well-characterized process in which
      embryo cells of seeds experience a programmed transition from quiescence to
      proliferation. For this reason they constitute a very good system to analyse
      nuclear evolution from a dehydrated practically inactive state until the steady
      state of proliferation. We analysed the temporal and spatial organization of
      transcription and splicing factors in nuclei of tomato radicle cells during
      germination. To address this issue we performed in situ immunodetection of
      several markers of these processes: the Z-DNA stretches forming behind the active
      RNA polymerases, the splicing proteins U2B'' and Sm, and the trimethyl guanosin
      cap of small nuclear RNA. The concomitant structural changes of the different
      nuclear compartments were studied in meristematic nuclei by electron microscopy
      and high-resolution cytochemistry for DNA and ribonucleoproteins. RESULTS: In
      quiescent cells practically no Z-DNA stretches were detected and splicing
      components localized mainly to one or two Cajal bodies associated to the
      nucleolus. In early germination, a massive de-condensation of chromatin and
      nucleolar Z-DNA conformation stretches were first detected, followed by the
      relocation of scarce splicing components to the small interchromatin spaces.
      Nucleoplasmic Z-DNA stretches were not detected until 4 h of imbibition and were
      accompanied by an important increase of splicing components in this nuclear
      domain. Soon after the post-germination stage, transcription and splicing
      topology and nuclear organization in meristematic nuclei resemble those in steady
      state growing tomato roots. CONCLUSIONS: Our results demonstrate that, in tomato,
      dormant nuclei splicing factors are stored in nucleolar Cajal bodies. In early
      germination, RNA polymerase I transcription is first activated, whereas mRNA
      transcription is fired later and is accompanied by a massive de-condensation of
      chromatin and accumulation of splicing factors in the interchromatin domains.
      Nucleoplasmic Cajal bodies appear later in germination.

PMID- 17439405
TI  - Mechanisms underlying vasorelaxant action of astragaloside IV in isolated rat
      aortic rings.
AB  - 1. Astragaloside IV is a component from the widely used traditional Chinese herb
      Astragalus membranaceus and its effect on rat aortic ring contraction and
      relaxation were investigated. 2. The aorta from male Sprague-Dawley rats was
      isolated in an organ bath and ring tension was recorded with or without
      endothelium. Cumulative effects of astragaloside IV on vessel contraction and
      relaxation were observed in the presence of various antagonists related to vessel
      activity. 3. Astragaloside IV showed concentration-dependent inhibition of vessel
      contraction induced by phenylephrine and potassium chloride. The amount of
      calcium released from intracellular stores sensitive to phenylephrine was also
      markedly reduced by astragaloside IV. There was dose-dependent vasorelaxation in
      endothelium-intact rings, which was partly inhibited by pre-incubation with
      nitric oxide (NO) synthase (NOS) Nomega-nitro-L-arginine methyl ester and
      guanylate cyclase inhibitor, 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one.
      Astragaloside IV also induced a significant increase in aortic tissue content of
      guanosine 3",5"-cyclic monophosphate (cGMP) both in vivo and in vitro.
      Endothelial NOS inhibitor Nomega-nitro-L-arginine prevented vasodilatation,
      whereas neuronal NOS inhibitor 7-nitroindazole did not show significant influence
      on the vessel relaxation of astragaloside IV. 4. In conclusion, astragaloside IV
      inhibited vessel contraction through blocking calcium influx and intracellular
      calcium release. The endothelium-dependent vessel dilation of astragaloside IV
      was attributed mainly to the endothelium-dependent NO-cGMP pathway.

PMID- 17439406
TI  - Protective role of a novel erythrocyte-derived depressing factor on blood vessels
      of renovascular hypertensive rats.
AB  - 1. We have isolated a novel human erythrocyte-derived depressing factor (EDDF)
      that has a significant antihypertensive effect in various rat models of
      hypertension. The aim of the present study was to examine the mechanisms of
      action of EDDF on vascular function in two-kidney, one-clip (2K1C) renovascular
      hypertensive rats. 2. The EDDF was prepared from human erythrocytes. Experiments
      were performed in 18 male Wistar rats. The vascular ring perfusion assay and a
      two-photon laser scanning fluorescence microscope (TMP) were used to evaluate the
      vascular contractile response. The effects of EDDF on phenylephrine (PE)- and
      noradrenaline (NA)-induced vascular contraction were evaluated in 2K1C
      hypertensive rats. The proliferation and DNA synthesis in vascular smooth muscle
      cells (VSMC) were determined using the [3H]-TdR (thymidine) incorporation and 3
      (4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Flow
      cytometry, reverse transcription-polymerase chain reaction and western blots were
      used to measure cell cycle and apoptotic profiles, platelet-derived growth factor
      (PDGF)-A expression and the activity of extracellular signal-regulated kinase
      (ERK)-1/2, as well as the expression of cyclin D1 and cyclin-dependent kinase
      (CDK) 4. 3. At 10(-5) g/mL, EDDF significantly decreased the PE- and NA-induced
      hypertensive vascular contraction. In addition, EDDF inhibited DNA synthesis in
      primary VSMC from 2K1C rats. The mRNA expression of PDGF-A in VSMC was twofold
      higher in 2K1C rats compared with control rats, whereas EDDF significantly
      inhibited the increment in PDGF-A mRNA expression. In addition, EDDF inhibited
      the phosphorylation of ERK1/2 and decreased the expression of cyclin D1 and CDK4;
      p21 (Cip1) levels were increased after treatment with EDDF. 4. In conclusion,
      EDDF inhibits VSMC proliferation in 2K1C rats through G0/G1 cell cycle arrest.
      The effects may be mediated, in part, by enhanced expression of p21 (Cip1) and
      the inhibition of ERK1/2 phosphorylation and the expression of cyclin D1/CDK4 and
      PDGF-A.

PMID- 17439407
TI  - Thymoquinone supplementation prevents the development of gentamicin-induced acute
      renal toxicity in rats.
AB  - 1. The present study investigated the possible protective effects of thymoquinone
      (TQ), a compound derived from Nigella sativa with strong anti-oxidant properties,
      against gentamicin (GM)-induced nephrotoxicity. 2. A total of 40 adult male
      Wistar albino rats was divided into four groups. Rats in the first group were
      injected daily with normal saline (2.5 mL/kg, i.p.) for 8 consecutive days,
      whereas rats in the second group received TQ (50 mg/L in drinking water) for 8
      consecutive days. Animals in the third group were injected daily with GM (80
      mg/kg, i.p.) for 8 consecutive days, whereas animals in the fourth group received
      a combination of GM (80 mg/kg, i.p.) and TQ (50 mg/L in drinking water) for 8
      consecutive days. 3. Gentamicin resulted in a significant increase in serum
      creatinine, blood urea nitrogen (BUN), thiobarbituric acid-reactive substances
      (TBARS) and total nitrate/nitrite (NOx) and a significant decrease in reduced
      glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT) and ATP levels in
      kidney tissues. 4. Interestingly, TQ supplementation resulted in a complete
      reversal of the GM-induced increase in BUN, creatinine, TBARS and NOx and
      decrease in GSH, GPx, CAT and ATP to control values. Moreover, histopathological
      examination of kidney tissues confirmed the biochemical data, wherein TQ
      supplementation prevents GM-induced degenerative changes in kidney tissues. 5.
      Data from the present study suggest that TQ supplementation prevents the
      development of GM-induced acute renal failure by a mechanism related, at least in
      part, to its ability to decrease oxidative stress and to preserve the activity of
      the anti-oxidant enzymes, as well as it ability to prevent the energy decline in
      kidney tissues.

PMID- 17439408
TI  - Establishment of rat precision-cut fibrotic liver slice technique and its
      application in verapamil metabolism.
AB  - 1. Liver fibrosis is the compensatory state of cirrhosis. In the long
      asymptomatic period, it is imperative to select a proper dosing regimen for drugs
      that are applicable to hepatic fibrosis. Otherwise, progressive deterioration to
      uncompensated cirrhosis may occur. The present study explored the characteristics
      of drug metabolism in fibrotic liver. 2. A rat precision-cut fibrotic liver slice
      (PCFLS) technique was established and the metabolism of verapamil was studied
      employing this technique. A rat hepatic fibrosis model was successfully induced
      integrating complex factors that included a high-fat diet, alcohol and CCl4. The
      PCFLS were incubated under different conditions and lactate dehydrogenase
      leakage, glutathione S-transferase activity and 3[4,5-dimethythiazole-2-yl]-2,5
      diphenyltetrazolium bromide reduction were used as indices to assess PCFLS
      viability. Activities of phase I and phase II metabolizing enzymes were monitored
      following treatment with cytochrome P450 (CYP) inducers. Normal and fibrotic
      liver slices were incubated individually with 10 micromol/L verapamil. The
      concentration of verapamil in the medium was determined by high-performance
      liquid chromatography and intrinsic clearance (Cl(int)) was calculated on the
      basis of the concentration-time curve. 3. The results showed that the PCFLS
      viability remained steady throughout the 6 h of culture when the thickness of
      slices was 300 microm and pH of the medium was 7.0; CYP inducers (phenobarbital
      and ethanol) enhanced CYP2E1, CYP3A1/2 and uridine diphosphate-glucuronate
      transferase (UDPGT) activities, respectively, in a time-dependent manner. The
      Cl(int) (microL/min per mg) values differed significantly between normal (9.7 +/-
      1.8) and fibrotic (5.6 +/- 1.4) liver slices (P < 0.01). 4. These results
      suggested that the PCFLS could remain viable for 2-6 h under appropriate
      conditions. The stability and inducibility of drug-metabolizing enzymes of PCFLS
      were also demonstrated. Furthermore, the metabolic rate of verapamil in PCFLS was
      decreased. These findings add further support to the use of PCFLS as a tool to
      study drug metabolism and to guide clinical medication.

PMID- 17439409
TI  - Studies with ketamine and alfentanil following Freund's complete adjuvant-induced
      inflammation in rats.
AB  - 1. N-Methyl-D-aspartate (NMDA) receptor antagonists suppress inflammatory
      hyperalgesia and the development of acute opioid tolerance. They may also enhance
      opioid-induced antinociception, while suppressing postopioid-induced hyperalgesia
      and opioid-enhanced inflammatory hyperalgesia. 2. The non-competitive NMDA
      receptor antagonist, ketamine, is a racemic chiral drug; its individual
      enantiomers have differing affinities for the NMDA receptor. The anaesthetic and
      antinociceptive potencies of (S)-ketamine are 1.5- and threefold higher,
      respectively, than those of (R)-ketamine in laboratory rodents. 3. The present
      study investigated the effects of racemic ketamine and enantiopure (S)-ketamine
      on inflammatory hyperalgesia in rats, 5 days after intraplantar injection of
      Freund's complete adjuvant (FCA) into one hind paw. First, racemic or (S)
      ketamine was administered alone; second, racemic or (S)-ketamine was administered
      30 min after initiation of i.v. infusions of the micro-opioid agonist,
      alfentanil. 4. Area under the curve (AUC) values for Von Frey paw withdrawal
      threshold (PWT) versus time curves were significantly increased (P < 0.05) for
      both inflamed and non-inflamed hind paws by racemic and (S)-ketamine (5 & 10
      mg/kg, s.c.). Similarly, AUC values for reduction of hind paw volume versus time
      were significantly increased (P < 0.05) by racemic and (S)-ketamine (10 mg/kg,
      s.c.). 5. Alfentanil infusions significantly increased PWT in both hind paws, but
      neither racemic nor (S)-ketamine (5 mg/kg, s.c.) administered 30 min after
      initiation of alfentanil infusion produced further increases in PWT. 6. Racemic
      and (S)-ketamine produced antinociceptive effects in both hind paws, but an
      antihyperalgesic effect per se was not apparent. Additionally, there was a
      possible anti-inflammatory effect of both drugs in the inflamed hind paw. These
      findings complement previous studies in which non-competitive NMDA receptor
      antagonists suppressed behavioural hyperalgesia. 7. However, racemic and (S)
      ketamine did not further enhance alfentanil's antinociceptive effects, although
      they appeared to prolong alfentanil's antinociceptive effects in the non-inflamed
      hind paw. These findings suggest that factors such as time-course, frequency and
      the mode of administration of NMDA receptor antagonists, in addition to the type
      of antinociceptive model (i.e. inflammatory compared with acute) and the
      nociceptive testing procedure (i.e. noxious mechanical compared with low
      threshold stimuli) may influence their effects on opioid-induced antinociception.

PMID- 17439410
TI  - Cyp2c19 genotype and omeprazole hydroxylation phenotype in Chinese Li population.
AB  - 1. CYP2C19 is a polymorphism of cytochrome P450, which is responsible for the
      metabolism of many drugs. The genetic polymorphism shows interethnic variation
      and it has been demonstrated that the frequency of poor metabolizers (PM) and the
      distribution of alleles of CYP2C19 vary among Chinese ethnic nationalities. The
      aim of the present study was to investigate the incidence of CYP2C19 polymorphism
      in the Chinese Li population. 2. One hundred and sixty-five unrelated healthy Li
      subjects were identified with respect to CYP2C19 by genotype and phenotype
      analysis. A polymerase chain reaction-restriction fragment length polymorphism
      method was performed for genotyping. The plasma concentrations of omeprazole and
      5-hydroxyomeprazole were assayed by reversed-phase high-performance liquid
      chromatography and the omeprazole hydroxylation index (HI) was determined. 3. The
      frequency distribution of omeprazole HI is bimodal and the antimode for HI was
      estimated to be 5.6. The prevalence of phenotypic PM in the Li population was
      16.6% (13.7-19.5; 95% CI). Genotype analysis revealed that the frequencies of the
      CYP2C19*1, *2 and *3 alleles in the Li population were 0.617 (0.590-0.644; 95%
      CI), 0.353 (0.327-0.379; 95% CI) and 0.031 (0.021-0.041; 95% CI), respectively.
      The frequency of genotypic PM was 14.7% (11.9-17.5; 95% CI), which almost agreed
      with the frequency of phenotypic PM. Omeprazole HI was significantly different
      among the different genotype groups (P < 0.05). 4. The present study revealed
      that the incidence of the CYP2C19*1, *2 and *3 alleles in Chinese Li population
      is different to that in other ethnic populations of China. There was an obvious
      relationship between CYP2C19 genotype and omeprazole hydroxylation phenotype, and
      about 90% of phenotypic PM can be explained by the CYP2C19*2 and *3 alleles.

PMID- 17439411
TI  - Stress-dependent induction of protein oxidation, lipid peroxidation and anti
      oxidants in peripheral tissues of rats: comparison of three stress models
      (immobilization, cold and immobilization-cold).
AB  - 1. It is known that stress causes disruption of homeostasis and an imbalanced
      anti-oxidant status in several organs. The aim of the present study was to
      determine the effects of three stress models on protein oxidation, lipid
      peroxidation and anti-oxidant enzyme activities in the liver, kidney and heart,
      and to investigate the relationship between corticosterone and some oxidative
      stress parameters. In addition, we investigated the most effective stress model
      for each parameter in each tissue. 2. Thirty-six male Wistar rats (aged 3 months
      old, weighing 220 +/- 20 g) were divided randomly into four groups of nine rats
      each: control (C), immobilization stress (IS), cold stress (CS), and
      immobilization-cold stress (ICS). 3. Results showed that corticosterone levels
      were increased in all stress groups. Levels of protein carbonyl (PC), conjugated
      dienes (CD) and thiobarbituric acid-reactive substances (TBARS) were increased,
      whereas reduced glutathione (GSH) levels were decreased in all tissues of all
      stress groups. Copper, zinc-superoxide dismutase (Cu,Zn-SOD) activities were
      increased in the liver and kidney of all stress groups, but were decreased in
      heart of the IS and CS groups. Catalase (CAT) activities were increased in liver
      of the CS group and in kidney and heart of all stress groups, but were decreased
      in liver of the IS and ICS groups. Selenium-dependent glutathione peroxidase (Se
      GSH-Px) activities were increased in liver of the CS and ICS groups and in heart
      of all stress groups, but were decreased in kidney of the IS group. Also, Se-GSH
      Px activity levels remained unchanged in liver of the IS group and in kidney of
      the CS and ICS groups. The increased CAT activity and unchanged Se-GSH-Px
      activity observed in kidney suggest that H2O2 may be primarily scavenged by CAT.
      4. The strong correlations between corticosterone and oxidative damage markers
      (e.g. protein oxidation, lipid peroxidation and GSH levels) suggest a
      relationship between these parameters. Liver was affected most by the CS model,
      whereas kidney and heart were affected most by ICS model. Stress-induced changes
      in the activities of anti-oxidant enzymes and GSH levels were found to be tissue-
      and enzyme-specific. In conclusion, results of the present study suggest that
      each stress model affects the different organ tissues in different ways.

PMID- 17439412
TI  - Influence of gender on oxidative stress, lipid peroxidation, protein damage and
      apoptosis in hearts and brains from spontaneously hypertensive rats.
AB  - 1. Hypertension leads to oxidative stress, lipid and protein damage, apoptosis
      and impaired cardiac contractile function. However, impact of gender on these
      hypertension-associated abnormalities has not been elucidated. 2. The present
      study evaluated the oxidative stress, lipid/protein damage, apoptosis in heart
      and brain tissues as well as cardiomyocyte contractile function in Wistar Kyoto
      (WKY) and spontaneously hypertensive rats (SHR) of both genders. Oxidative
      stress, lipid peroxidation, protein damage and apoptosis were assessed by
      glutathione (GSH) : reduced glutathione (GSSG) ratio, malondialdehyde (MDA)
      levels, protein carbonyl levels and caspase-3 activity, respectively.
      Cardiomyocyte contractile function was examined including peak shortening (PS),
      time-to-PS (TPS), time-to-90% relengthening (TR90) and maximal velocity of
      shortening/relengthening (+/-dL/dt). The SHR cardiomyocytes displayed reduced PS
      and +/-dL/dt compared with gender-matched WKY counterparts. Male but not female
      SHR cardiomyocytes possessed longer resting cell length, normal TPS and prolonged
      TR90. All mechanical parameters were comparable between male and female WKY rats
      with the exception of a higher TR90 in females. Hypertension did not
      significantly affect the GSH : GSSG ratio in the heart and brain tissues of
      either gender. Brain from female WKY rats displayed a reduced GSH : GSSG ratio.
      The MDA levels were unchanged and elevated, respectively, in SHR heart and SHR
      brain tissues from both genders. Protein carbonyl formation and caspase-3
      activity were elevated in male but not female SHR hearts. Nonetheless, brain
      protein carbonyl level and caspase-3 activity were unaffected by hypertension or
      gender. 3. In summary, these results suggest that gender affects hypertension
      associated oxidative stress, lipid and protein damage, apoptosis in heart and
      brain tissues and cardiomyocyte contractile function.

PMID- 17439413
TI  - CB1 receptor activation in the basolateral amygdala produces antinociception in
      animal models of acute and tonic nociception.
AB  - 1. Recent studies have suggested that the basolateral nucleus of the amygdala
      (BLA) participates in the processing of pain information, especially noxious
      somatic information. Cannabinoid receptors or CB1 mRNA are expressed more in the
      BLA than in other nuclei of the amygdala. Thus, the aim of the present study was
      to examine whether CB1 receptors in the BLA may be involved in modulating acute
      and/or tonic nociceptive processing. 2. Adult rats were exposed to intra-BLA
      microinjection of the cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl
      3-(4-morpholinylmethyl) pyrrolo [1,2,3,-de]-1,4-benzoxazin-6-yl]-1
      naphthalenylmethanone mesylate [WIN 55,212-2 (1, 2.5, 5 or 10 microg/side)] and
      subjected to the tail flick and formalin tests. 3. The rats demonstrated a dose
      dependent increase in latency to withdraw from a thermal noxious stimulus in the
      tail flick test and a decrease in formalin-induced pain behaviours. The
      antinociceptive effects of the CB1 receptor agonist WIN 55,212-2 (10 microg/side)
      in both tests were attenuated in the presence of the selective CB1 receptor
      antagonist, N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl
      1H-pyrazole-3- carboxamide (AM251; 0.55 ng/side). Administration of the CB1
      receptor antagonist AM251 (0.55, 5.5, or 55.5 ng/side) alone did not alter the
      nociceptive thresholds in either test. Bilateral microinjection of the selective
      CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]
      5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528;
      1 microg/side) had no effect on the antinociception produced by WIN 55,212-2,
      suggesting that the antinociceptive actions of WIN 55,212-2 are mediated by CB1
      receptors. 4. The findings suggest the existence of a CB1-mediated inhibitory
      system in the BLA that, when activated, can diminish responsivity to acute and
      tonic noxious stimuli, but that normally has no tonic effect on the response
      threshold of these stimuli.

PMID- 17439414
TI  - siRNA-mediated Bcl-2 and Bcl-xl gene silencing sensitizes human hepatoblastoma
      cells to chemotherapeutic drugs.
AB  - 1. The aim of the present study was to investigate the changes in
      chemotherapeutic drug sensitivity of HepG2 cells transfected with Bcl-2 and Bcl
      xl siRNA expression vectors. 2. Bcl-2 and Bcl-xl siRNA and negative siRNA
      expression vectors were constructed and stably transfected into HepG2 cells.
      Reverse transcriptase-polymerase chain reaction was used to detect the target
      gene expression, and the Bcl-2, Bcl-xl, Bax and caspase-3 protein levels were
      measured using western blots and immunofluorescence. The sensitivity of the cells
      to the chemotherapeutic drugs 5-fluorouracil (5-FU) and 10-hydroxycamptothecin
      (HCPT) was analysed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl
      tetrazoliumbromide (MTT) and flow cytometry. 3. The Bcl-2 and Bcl-xl gene
      expression and corresponding protein levels in Bcl-2 siRNA, Bcl-xl siRNA and Bcl
      2/Bcl-xl siRNA transfected cells were reduced compared with negative siRNA
      transfected or untreated cells. The Bax protein level remained unaltered but the
      caspase-3 level was enhanced when Bcl-2 and Bcl-xl protein levels were reduced.
      The MTT results demonstrated that Bcl-2 and Bcl-xl transfected cells exhibited
      increased sensitivity to 5-FU or HCPT. Flow cytometry demonstrated that the sub
      G1 cell population increased in Bcl-2/Bcl-xl siRNA co-transfected and Bcl-xl
      siRNA and Bcl-2 siRNA transfected cells when compared with negative siRNA or
      untreated cells. The latter trend was strengthened further in the presence of 5
      FU or HCPT. 4. Thus, Bcl-2 and Bcl-xl siRNA-mediated gene silencing, in
      combination with chemotherapy, may be a potential therapeutic strategy against
      human hepatoblastoma.

PMID- 17439415
TI  - Rosiglitazone, an agonist of peroxisome proliferator-activated receptor-gamma,
      prevents contralateral testicular ischaemia-reperfusion injury in prepubertal
      rats.
AB  - 1. Rosiglitazone plays a positive role in the reparation of ischaemia-reperfusion
      (I/R) injury in different tissues. Thus, we examined its biochemical and
      histological effects on the contralateral testes to determine whether exogenous
      rosiglitazone affords any protection against testicular damage. 2. Forty-eight
      prepubertal male Wistar-Albino rats were divided into six groups. Testicular
      torsion was created by rotating the right testis 720 degrees in a clockwise
      direction for 5 h in all groups except group I, which was the sham-control group.
      In group II, bilateral orchiectomy was performed following the torsion period.
      After detorsion both testes were removed in the fifth hour in group III and on
      the seventh day in group IV. In group V, one-shot rosiglitazone (4 mg/kg) was
      administered 40 min before detorsion and both testes were removed following the
      torsion period. In group VI, rosiglitazone was administered (4 mg/kg) 40 min
      before detorsion and for 7 days, and then both testes were harvested. The tissue
      levels of malondialdehyde (MDA) were measured and mean testicular biopsy score
      (MTBS) and mean seminiferous tubule diameter (MSTD) were examined.
      Immunoexpression of endothelial nitric oxide synthase (eNOS) in testes tissues
      was investigated by immunohistochemical studies. 3. In the contralateral testis,
      the MTBS and MSTD values of group VI were significantly higher than those in
      group IV. Immunohistochemically, mild eNOS immunostaining was present in the germ
      cells of the contralateral testes in group IV after I/R. In group VI, intense
      eNOS immunoreactivity was seen in the contralateral testes. 4. Rosiglitazone
      reduces contralateral testicular damage formed after unilateral testicular
      torsion and alleviates the oxidative events.

PMID- 17439416
TI  - 5-HT1A receptor agonist properties of antipsychotics determined by [35S]GTPgammaS
      binding in rat hippocampal membranes.
AB  - 1. 5-Hydroxytryptamine 1A (5-HT1A) receptors have attracted increasing attention
      as a promising target for antipsychotic therapy. Although many atypical
      antipsychotic drugs, including the prototype clozapine, have been reported to be
      partial agonists at 5-HT1A receptors, these results are often fragmental and
      derived mainly from experiments that used cultured cells. 2. In the present
      study, [35S]guanosine 5'-O-(3-thiotriphosphate) ([35S]GTPgammaS) binding assay in
      rat hippocampal membranes was applied to a series of antipsychotic drugs,
      especially atypical antipsychotics. 3. Most, but not all, of atypical
      antipsychotic drugs and the classical antipsychotic drug nemonapride behaved as
      partial agonists at 5-HT1A receptors with varied potencies and relative
      efficacies. The most potent compound was perospirone with a mean EC50 of 27
      nmol/L, followed by aripiprazole (45 nmol/L) > ziprasidone (480 nmol/L) >
      nemonapride (790 nmol/L) > clozapine (3900 nmol/L) > quetiapine (26,000 nmol/L).
      The maximal percentage increases over the basal binding (%Emax) for these
      antipsychotic drugs were 30-50%, with the exception of perospirone (approximately
      15%), whereas 5-HT stimulated the binding to a mean %Emax of 105%. 4. Increasing
      concentrations of the selective and neutral 5-HT1A antagonist WAY100635 shifted
      the concentration-response curve of nemonapride-stimulated [35S]GTPgammaS binding
      to the right and in parallel. 5. The relative efficacy or intrinsic activity of a
      compound was affected differently by the differing concentrations of guanosine
      diphosphate (GDP) in the assay buffer, which should be taken into consideration
      when determining the relative efficacies of these antipsychotics as 5-HT1A
      receptor agonists. 6. These results provide important information concerning the
      relevance of 5-HT1A receptor partial agonist properties in the treatment for
      schizophrenic patients with most, if not all, of atypical antipsychotic drugs.

PMID- 17439417
TI  - Protective effects of vitamins C and E against endometrial damage and oxidative
      stress in fluoride intoxication.
AB  - 1. Fluoride (F) is an essential trace element that has protective effects against
      bone mineral loss. However, it becomes toxic at higher doses and induces some
      adverse effects on a number of physiological functions, including reproduction.
      The aims of this study were to examine F-induced oxidative stress that promotes
      production of reactive oxygen species (ROS) and to investigate the role of
      vitamins C and E against possible F-induced endometrial impairment in rats. 2.
      Rats were divided into three groups: control, F and F plus vitamins. The F group
      was given 100 mg/L orally for 60 days. Combined vitamins were also administered
      orally. Fluoride administration to control rats significantly increased
      endometrial malondialdehyde (MDA) but decreased superoxide dismutase (SOD),
      glutathione peroxidase (GSH-Px) and catalase (CAT) activities. Endometrial
      glandular and stromal apoptosis were investigated by DNA nick end-labelling
      (TUNEL) method on each sample and the mean endometrial apoptotic index (AI) was
      calculated. 3. Vitamin administration with F treatment caused endometrial MDA to
      decrease, but SOD, GSH-Px and CAT activities to increase, all to significant
      levels. Vitamins showed a histopathological protection against F-induced
      endometrial damage. There was a significant difference in the AI between the
      groups. Lymphocyte and eosinophil infiltration in stroma in F-treated rats were
      more than those in the control and F + Vit groups. 4. It can be concluded that
      oxidative endometrial damage plays an important role in F-induced endometrial
      toxicity, and the modulation of oxidative stress with vitamins reduces F-induced
      endometrial damage both at the biochemical and histological levels.

PMID- 17439418
TI  - Lack of blood pressure salt-sensitivity supports a preglomerular site of action
      of nitric oxide in Type I diabetic rats.
AB  - 1. The relationship between sodium intake and blood pressure is affected
      differently by changes in angiotensin (Ang) II and preglomerular resistance, and
      this study measured that relationship to evaluate the link between nitric oxide
      and blood pressure early in diabetes. 2. Rats were chronically instrumented,
      placed on high-sodium (HS = 12 mEq/d) or low-sodium (LS = 0.07 mEq/d) intake
      diets and assigned to either vehicle- (V) or Nomega-nitro-L-arginine methyl ester
      (L-NAME; L) treated groups. Mean arterial pressure (MAP) was measured 18 h/day
      for a 6-day control and 14-day streptozotocin diabetic period in each animal. 3.
      The MAP of the control period averaged 95 +/- 1 and 94 +/- 1 mmHg in the LSV and
      HSV rats and 116 +/- 2 and 124 +/- 1 mmHg in the LSL and HSL rats, respectively
      (LSL vs HSL was significant at P < 0.05). Diabetes increased MAP only in the LSL
      and HSL rats to 141 +/- 2 mmHg and 152 +/- 2, respectively, similar to our
      previous reports, and those respective 25 and 28 mmHg increases were a parallel
      shift in the pressure natriuresis relationship. However, the apparent difference
      between the LSL and HSL groups when compared was a parallel of the control MAP
      difference. Plasma renin activity (PRA) in the control period averaged 1.5 +/-
      0.5 and 8.1 +/- 1.8 ng AI/mL per h in the HSV and LSV rats, and 0.8 +/- 0.2 and
      2.8 +/- 0.5 ng AI/mL per h in the HSL and LSL rats, respectively, and increased
      similarly by 4.6-fold in the HSL and 4.8-fold in the LSL rats during diabetes.
      Glomerular filtration rate (GFR) increased in the vehicle but not the L-NAME
      treated groups, consistent with our previous reports. 4. Thus, the hypertension
      caused by the onset of diabetes in L-NAME-treated rats was not salt-sensitive.
      The normal modulation of PRA by salt intake and the failure of GFR to increase
      are consistent with our hypothesis that nitric oxide may protect against
      hypertension early in diabetes by preventing preglomerular vasoconstriction by
      AngII.

PMID- 17439419
TI  - Endotoxin-induced acute lung injury and organ dysfunction are attenuated by
      pentobarbital anaesthesia.
AB  - 1. Acute lung injury (ALI) as a result of sepsis is a major cause of mortality.
      Certain anaesthetic agents have been reported to suppress pro-inflammatory
      cytokines and inducible nitric oxide (NO) synthase (iNOS) activities. We
      investigated the effects of pentobarbital on ALI and organ functions after the
      administration of endotoxin. 2. Intravenous (i.v.) pentobarbital (20 or 40 mg/kg)
      was administered 5 min after lipopolysaccharide (LPS; 10 or 30 mg/kg via i.v.
      infusion). To avoid hypoxia and/or hypercapnia following anaesthesia, we
      installed a special chamber connected to a rodent ventilator to provide
      ventilation with 95% oxygen content and 5% nitrogen. The animal was kept at
      eucapnic conditions (arterial PCO2 at an average of 38 +/- 2 mmHg). 3. We
      monitored the arterial pressure (AP) and heart rate (HR). Acute lung injury was
      evaluated by lung weight changes, protein concentration in bronchoalveolar
      lavage, and Evans blue leakage. Plasma nitrate/nitrite, methyl guanidine and
      biochemical factors were determined. Pathological and immunofluorescent
      examinations were performed to observe the lung changes and to determine the
      activities of pro-inflammatory cytokines, nitrotyrosine and iNOS. 4.
      Lipopolysaccharide caused dose-dependent systemic hypotension with an increase in
      the extent of ALI. The lung pathology included oedema and inflammatory cell
      infiltration. Accompanying the ALI, LPS elevated plasma nitrate/nitrite, methyl
      guanidine, blood urea nitrogen, lactic dehydrogenase, creatinine phosphokinase,
      glutamic transaminase and amylase. The lung tissue content of tumour necrosis
      factor-alpha, interleukin-lbeta, iNOS and nitrotyrosine was increased following
      LPS administration. These changes were abrogated by pentobarbital anaesthesia. 5.
      Our results indicated that pentobarbital anaesthesia significantly augmented the
      LPS-induced systemic hypotension. However, it attenuated the LPS-induced ALI and
      organ dysfunctions. This agent also improved the survival rate following LPS at
      high and low doses. This mechanism may be related to the inhibitory effects on
      the increases in the production or activity of NO, free radicals, pro
      inflammatory cytokines, nitrotyrosine and iNOS.

PMID- 17439420
TI  - The effects of isosteviol against myocardium injury induced by ischaemia
      reperfusion in the isolated guinea pig heart.
AB  - 1. This study aimed to investigate the protective effects of isosteviol against
      myocardial ischaemia-reperfusion (IR) injury and its effects on mitochondrial
      adenosine triphosphate (ATP)-sensitive potassium channel (mitoK(ATP)) activity in
      vitro. 2. Groups of eight guinea pigs were treated as follows: constant perfusion
      control (PC), IR control, ischaemic preconditioning (IPC) + IR, isosteviol (50,
      250 or 500 nmol) + IR, 5-hydroxydecanoate acid (5-HD) (5 micromol) + isosteviol
      (500 nmol) + IR. The guinea pig heart was isolated and perfused in Langendorff
      mode with modified Tyrode solution at a flow rate of 10 mL/min. Ischaemia was
      introduced for 30 min followed by reperfusion for 20 min. Cardiac function,
      coronary arterial flow rate, lactate dehydrogenase (LDH) and creatine kinase (CK)
      activities in the perfusate were measured prior to ischaemia and at the end of
      reperfusion. 3. There were no significant (P > 0.05) changes in cardiac function
      or markers of cell damage (i.e. activities of LDH and CK) in the PC group. In
      contrast, cardiac function was adversely affected in the IR group, with
      significant (P < 0.05) decreases in left ventricular developing pressure
      (LVDevP), dP/dt(max) and dP/dt(min) compared with baseline and the PC group. In
      addition, there were increases in activity of LDH (20%) and CK (67%) compared
      with baseline and the PC group. 4. Ischaemic preconditioning and pretreatment
      with isosteviol, at all dose levels, resulted in a significant (P < 0.05)
      attenuation of IR injury. Lactate dehydrogenase and CK activities were not
      significantly (P < 0.05) different compared with baseline. Isosteviol did not
      increase coronary flow, suggesting that the protective effect of isosteviol on
      the myocardium was not mediated by dilation of the coronary blood vessels. 5.
      Pretreatment with the mitoK(ATP) blocker 5-HD partially antagonized the effects
      of 500 nmol isosteviol, with a statistically significant attenuation of its
      protective effects on HR, LVDevP, dP/dt(max) and dP/dt(min) compared with
      isosteviol alone pretreatment. 6. The IR injury on the Langendorff perfused
      guinea pig heart was alleviated by isosteviol, which appears to mediate its
      effects through mitoK(ATP) channels. Future research might aim to investigate the
      interaction of isosteviol with mitoK(ATP) channels in order to clarify its
      mechanism of action.

PMID- 17439421
TI  - Drug-related hospital admissions in a generic pharmaceutical system.
AB  - 1. Generically based pharmaceutical systems exist in a few countries of the
      world, such as Iran. Most developed countries have free market pharmaceutical
      systems. Drug-related problems (DRP) have been reported mostly in the Western
      world but few data are available for generic systems. In this study, we tried to
      measure the prevalence of drug-related problems leading to hospital admissions in
      Isfahan, Iran. 2. One thousand consecutive hospital admissions in three major
      teaching hospitals were studied for a period of 6 months for the presence of DRP
      as a cause of hospital admissions. Two subcategories of DRP were considered: (i)
      drug therapy failure; and (ii) adverse drug reactions. Preventability and outcome
      measures were also assessed. Medications responsible for DRP were classified
      according to the Anatomic Therapeutic Chemical (ATC) classification of the World
      Health Organization. 3. Of the 1000 admissions studied, 115 (11.5%) were owing to
      DRP, 81% as a result of drug therapy failure and 19% as adverse drug reactions. A
      total of 106 out of the 115 DRP cases (92%) were either preventable or probably
      preventable, most of which had to do with either prescriber or patient error. An
      overview of DRP showed that 58.3% resulted in complete recovery, 33.9% in
      relative recovery and 7.8% in death. Close to 1% of hospital admissions resulted
      in DRP-related deaths. 4. The overall prevalence of hospital admissions caused by
      DRP is similar to that in free market pharmaceutical systems. The high
      preventability rate of these problems should alert clinicians and policy makers
      to design strategies to curtail this. Also, reasons for differences in subtypes
      of DRP between the results of this study and those of the literature from free
      market systems needs to be investigated further.

PMID- 17439422
TI  - Optimizing dosage of ketamine and xylazine in murine echocardiography.
AB  - 1. Ketamine and xylazine (KX) mixture is the most commonly used anaesthetic drug
      during echocardiography in mice to induce sedation and immobility. Nevertheless,
      the doses of KX reported in the literature vary substantially with associated
      significant difference in cardiac function. To explore the optimal KX dosage and
      observation time for murine echocardiography, we compared the effects of various
      KX combinations on echocardiographic measurement. 2. Mice were anaesthetized with
      ketamine (50 or 100 mg/kg) and xylazine (0-10 mg/kg). Echocardiography was
      performed 5, 10, 20 and 40 min after induction of anaesthesia. Also, cardiac
      function was assessed in mice with and without pressure-overload induced left
      ventricle (LV) hypertrophy and dysfunction, either under anaesthesia with KX or
      whilst conscious. 3. Ketamine at 100 mg/kg alone or together with xylazine at 0.1
      mg/kg was associated with a high and stable heart rate (HR), a high fractional
      shortening (FS) and produced the least effect on LV inner dimension at end of
      diastole (LVIDd). Ketamine and xylazine at 100 and 10 mg/kg, respectively,
      produced a lower and stable FS, but with a low and unstable HR. All other
      combinations resulted in depressed and unstable cardiac function during this
      period. 4. The dose-dependent suppression of FS by xylazine was counteracted
      partly by ketamine. 5. Although in the chronic pressure-overload model LV
      hypertrophy can be detected accurately in both the anaesthetized or conscious
      state, systolic dysfunction was masked partially by higher doses of xylazine (2.5
      or 10 mg/kg) combined with ketamine at 100 mg/kg. 6. With KX anaesthesia, both
      the dose of xylazine and the anaesthetic duration are critical in achieving an
      ideal condition for murine echocardiography. Ketamine at 100 mg/kg alone produces
      acceptable anaesthesia, stable cardiac function with a minimal depressant effect
      and is therefore recommended if single-dose anaesthetic is to be used.

PMID- 17439423
TI  - Writing intelligible English prose for biomedical journals.
AB  - 1. I present a combination of semi-objective and subjective evidence that the
      quality of English prose in biomedical scientific writing is deteriorating. 2. I
      consider seven possible strategies for reversing this apparent trend. These refer
      to a greater emphasis on good writing by students in schools and by university
      students, consulting books on science writing, one-on-one mentoring, using
      'scientific' measures to reveal lexical poverty, making use of freelance science
      editors and encouraging the editors of biomedical journals to pay more attention
      to the problem. 3. I conclude that a fruitful, long-term, strategy would be to
      encourage more biomedical scientists to embark on a career in science editing.
      This strategy requires a complementary initiative on the part of biomedical
      research institutions and universities to employ qualified science editors. 4. An
      immediately realisable strategy is to encourage postgraduate students in the
      biomedical sciences to undertake the service courses provided by many
      universities on writing English prose in general and scientific prose in
      particular. This strategy would require that heads of departments and supervisors
      urge their postgraduate students to attend such courses. 5. Two major publishers
      of biomedical journals, Blackwell Publications and Elsevier Science, now provide
      lists of commercial editing services on their web sites. I strongly recommend
      that authors intending to submit manuscripts to their journals (including
      Blackwell's Clinical and Experimental Pharmacology and Physiology) make use of
      these services. This recommendation applies especially to those for whom English
      is a second language.

PMID- 17439424
TI  - Slow inotropic response of intact left ventricle to sudden dilation critically
      depends on a myocardial dialysable factor.
AB  - 1. Slow inotropic response following a sudden myocardium stretch seems to be an
      autocrine/paracrine mechanism the basis of which is not yet completely defined.
      2. We compared the canine left ventricle (LV) response to sudden dilation when
      the LV was supported by the arterial blood of a support dog with when it was
      supported by an oxygenator + haemodialyser system. 3. A slow inotropic response
      (SIR) after dilation was seen in all six hearts supported by the donor dog,
      attaining 87 +/- 6% of immediate increase, whereas a mere 10% SIR occurred in
      only one out of seven hearts maintained by the oxygenator + haemodialyser. 4.
      These results indicate that SIR genesis involves one or more renewable components
      essential to the intracellular calcium gain elicited by stretch.

PMID- 17439425
TI  - Role of xanthine oxidase in dexamethasone-induced hypertension in rats.
AB  - 1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with
      nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO),
      which is implicated in the production of reactive oxygen species, in
      dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats
      were divided randomly into four treatment groups: saline, dexamethasone (dex),
      allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures
      (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as
      a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5.
      Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P <
      0.001) and bodyweights (P" < 0.01). Allopurinol decreased serum urate from 76 +/-
      5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2
      micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex
      HT. This, together with our previous findings that allopurinol failed to prevent
      adrenocorticotrophic hormone induced hypertension, suggests that XO activity is
      not a major determinant of GC-HT in the rat.

PMID- 17439426
TI  - Quantitative characterization of a repeated acute joint inflammation model in
      rats.
AB  - 1. Chronic pain owing to arthritis is a major clinical problem worldwide. To
      study the underlying pathological mechanisms of chronic pain and the
      effectiveness of different treatments, a number of experimental models have been
      developed over the years. 2. We introduced a new subchronic inflammatory model by
      repeated unilateral administration of carrageenan into the ankle joint of rats,
      and investigated the degree and the time-course of the oedema, and thermal and
      mechanical hyperalgesia. 3. Carrageenan (450 microg) was injected on three
      occasions (on days 1, 4 and 7), and the resulting oedema, thermal hyperalgesia
      (paw withdrawal test) and weight load were characterized in voluntarily walking
      rats daily for 15 days. The effect of diclofenac sodium (3 mg/kg orally daily for
      15 days) was also determined. 4. Repetitive administration of carrageenan caused
      fluctuating oedema and pain responses, which did not normalize within 3 days.
      Exacerbated inflammatory oedema was observed after the second and third
      injections. Oedema and a decreased weight load of the inflamed paw were observed
      throughout the investigation period, and paw withdrawal thresholds to noxious
      thermal stimuli returned to baseline pre-carrageenan values from Day 13. 5. Oral
      diclofenac (3 mg/kg daily for 15 days) significantly decreased oedema within a
      few days (Day 3), whereas its anti-allodynic effect developed only several days
      later (Day 9). However, diclofenac at the applied dose did not influence the
      thermal hyperalgesia. 6. The results suggest that the repeated administration of
      carrageenan might be a suitable model for determining the effects of long-lasting
      treatment.

PMID- 17439428
TI  - Progenitor cells and adult neurogenesis in neurodegenerative diseases and
      injuries of the basal ganglia.
AB  - 1. The subventricular zone (SVZ) of the forebrain that overlies the caudate
      nucleus is one of the principal brain regions in which neurogenesis occurs in the
      human brain, throughout life. 2. In response to the degeneration that occurs in
      the caudate nucleus in Huntington's disease, or in the caudate nucleus or cortex
      in stroke models, the SVZ increases the production of progenitor cells that
      migrate towards the site of the damage where they can differentiate into mature
      neurons and glial cells. The SVZ contains three main cell types and these are
      progenitor cells, glial cells and migratory neuroblasts; glial cells are the most
      common cell type and, in response to Huntington's disease, most of the SVZ cell
      proliferation is glial, but the number of precursor and neuroblasts is also
      increased. 3. The SVZ is enriched in neuroactive compounds, such as neuropeptide
      Y and gamma-aminobutyric acid receptor subunits gamma2, which stimulate ongoing
      neurogenesis. Interestingly, these stimulating cues are upregulated in the SVZ in
      response to Huntington's disease. Thus, the SVZ comprises heterogeneous cell
      types that are maintained in an environment that is permissive to neurogenesis
      and gliogenesis, and responds to neurodegenerative changes in adjacent brain
      regions by increasing progenitor cell proliferation and neurogenesis in an
      attempt to replace the cells that die as a result of neurodegeneration.

PMID- 17439429
TI  - Regulators of adult neurogenesis in the healthy and diseased brain.
AB  - 1. In recent decades evidence has accumulated demonstrating the birth and
      functional integration of new neurons in specific regions of the adult mammalian
      brain, including the dentate gyrus of the hippocampus and the subventricular
      zone. 2. Studies in a variety of models have revealed genetic, environmental and
      pharmacological factors that regulate adult neurogenesis. The present review
      examines some of the molecular and cellular mechanisms that could be mediating
      these regulatory effects in both the normal and dysfunctional brain. 3. The
      dysregulation of adult neurogenesis may contribute to the pathogenesis of
      neurodegenerative disorders, such as Huntington's, Alzheimer's and Parkinson's
      disease, as well as psychiatric disorders such as depression. Recent evidence
      supports this idea and, furthermore, also indicates that factors promoting
      neurogenesis can modify the onset and progression of specific brain disorders,
      including Huntington's disease and depression.

PMID- 17439430
TI  - 5-HT7, neurogenesis and antidepressants: a promising therapeutic axis for
      treating depression.
AB  - 1. There is mounting evidence that a wide range of antidepressants share the
      common feature of increasing hippocampal neurogenesis. The specificity of this
      association has suggested that an ability to increase neurogenesis might be a
      useful paradigm to screen for compounds with antidepressant activity. 2. The hope
      of developing better antidepressants has stimulated research into the molecular
      control of neurogenesis and here we summarize some of the recent findings. We
      also review recent work that highlights 5-HT7 receptor as a promising molecular
      target in the treatment of depression. 3. In summary, it appears that 5-HT7
      antagonism is capable of producing diverse antidepressant-like behavioural
      effects, alters hippocampal neuronal morphology and synergistically regulates
      hippocampal neurogenesis.

PMID- 17439432
TI  - Participatory evaluation (I)--sharing lessons from fieldwork in Asia.
AB  - BACKGROUND: There is a need to study methodologies for evaluating social
      development projects. Traditional methods of evaluation are often not able to
      capture or measure the 'spirit of change' in people, which is the very essence of
      human development. Using participatory methodologies is a positive way to ensure
      that evaluations encourage an understanding of the value of critical analysis
      among service providers and other stakeholders. Participatory evaluation provides
      a systematic process of learning through experiences. METHODS: Practical
      experiences of conducting a number of evaluation studies in social development
      projects have led the author to develop four basic principles of participatory
      evaluation strategies. This has been further conceptualized through an extensive
      literature search. The article develops and shares these principles through
      descriptions of field experiences in Asia. RESULTS: The article illustrates that
      the role of any evaluation remains a learning process, one which promotes a
      climate of reflection and self-assessment. It shows how using participatory
      methods can create this environment of learning. However, one needs to keep in
      mind that participatory evaluation takes time, and that the role and calibre of
      the facilitator are crucial. CONCLUSION: Participatory evaluation methods have
      been recommended for social development projects to ensure that stakeholders
      remain in control of their own lives and decisions.

PMID- 17439433
TI  - Participatory evaluation (II)--translating concepts of reliability and validity
      in fieldwork.
AB  - BACKGROUND: In developing countries participatory methods are a viable way of
      evaluating social development projects. It provides a means to look
      constructively at the strengths and weaknesses in projects, and use the lessons
      learned to improve planning and implementation. One of the challenges faced,
      however, is being able to ensure that the study is sound, reliable and valid, and
      that it is free from bias, thus making the final results trustworthy and of use
      to a larger population. METHODS: This article looks at five steps involved in a
      participatory evaluation process and the ways in which reliability and validity
      have been considered. RESULTS: Participatory studies may be different, but all
      have similar underlying principles as traditional quantitative and qualitative
      studies. Examples from fieldwork in Asia have been used to demonstrate how
      studies can be made credible, so that they have value, influence or the ability
      to encourage changes in thinking, while evaluating social development projects.
      At every stage, the role of the external evaluator remains crucial, and has to be
      that of a facilitator, encouraging participation from everyone. CONCLUSION: Hence
      project evaluations using such a method must be clear in how to remove bias and
      ensure reliability and validity in all the stages of the evaluation, from
      planning to making recommendations. Imaginative and alternative strategies need
      to be developed to examine reliability and validity in the qualitative
      evaluation.

PMID- 17439434
TI  - Unmet health, welfare and educational needs of disabled children in an
      impoverished South African peri-urban township.
AB  - BACKGROUND: Childhood disability in South Africa has failed to receive adequate
      attention from governmental agencies, such as the health, education and social
      welfare departments, despite there being more than 1 million disabled children in
      the country. This study sought to assess the unmet rehabilitation, education and
      welfare needs of disabled children living in a peri-urban township. METHODS: As
      no register of disabled children existed, snowball sampling was used to recruit a
      convenience sample of 156 disabled children living in Orange Farm township near
      Soweto, South Africa. Children's impairments, their health and educational needs,
      and the availability and utilization of services were assessed using a structured
      interview. RESULTS: Few disabled children attended pre-school (35%) or school
      (44%). Only a quarter (26%) of children in need of rehabilitation received such
      services. Children with motor impairments were more likely to receive
      rehabilitation than those with intellectual impairment (44% vs. 8%, P < 0.0001).
      Of the 233 assistive devices required, only 64 (28%) had been issued. Less than
      half (45%) of the children entitled to a social assistance grant were receiving
      it. Lack of money, limited awareness about available services, and bureaucratic
      obstacles were the main reasons offered by caregivers for the low utilization of
      available services and resources. CONCLUSION: Children with disabilities living
      in Orange Farm are not enjoying the rights and services to which they are
      entitled. Innovative, co-ordinated service delivery strategies, and better
      informed caregivers combined with community recognition of, and support for, the
      needs of disabled children are required to address these unmet needs.

PMID- 17439435
TI  - Caregiver experiences, contextualizations and understandings of the burn injury
      to their child. Accounts from low-income settings in South Africa.
AB  - BACKGROUND: Childhood burn injury is a widespread phenomenon with a
      disproportionate concentration in Sub-Saharan Africa. Burn injuries may have far
      reaching and traumatic interpersonal, social and occupational effects for young
      children. There has been scant attention to the caregiver's experience of these
      events. This study sought to explore the caregiver's understanding of the injury
      to their children, the injury causes and its preventability. METHODS: The study
      is based on interviews with 13 caregivers. All informants were the female parents
      or grandparent of children who had sustained a moderate to severe burn injury and
      presented at a children's hospital in Cape Town. The interviews were audio
      recorded, transcribed verbatim and analysed using a synthesis of the grounded
      theory approach with core content analytic steps. RESULTS: Analysis of data
      indicates that information related to the injury event can be separated into the
      child's activities, the activity undertaken by the caregiver at the time of the
      event and the environmental hazards coming into play. The remote factors
      associated with the event were related to the individual caregiver, family
      circumstances, the area's living conditions and the cultural context. The
      caregivers' suggestions for the future focused on the isolation of heat sources,
      caregiver supervision and environmental renovations. CONCLUSIONS: Caregivers
      emphasized the multifactorial nature of the burn injury event and highlighted the
      adverse environmental, domestic and personal circumstances to their child's burn
      injury. Their recommendations for burn prevention avoidance and control are
      consistent with their understanding of the injury aetiology and demonstrate a
      synergy with public health recommendations for environmental and technological
      interventions.

PMID- 17439436
TI  - Exposure of young children working on Mexican tobacco plantations to
      organophosphorous and carbamic pesticides, indicated by cholinesterase
      depression.
AB  - BACKGROUND: Organophosphorous (OP) and carbamic pesticides are used in large
      quantities on tobacco plantations in Nayarit State, Mexico, where up to 3000
      children and their families work. OP and carbamic pesticides are easily inhaled
      or absorbed through the skin and children may be particularly vulnerable to
      pesticides because of their smaller body mass, their height and more regular hand
      mouth contact. The aim of this study is to assess the effect of pesticide
      exposure on acetylcholinesterase levels of very young migrant Mexican tobacco
      workers and younger siblings. METHODS: Blood samples were collected from 160
      children aged 0-14 years during harvest (exposure) and from 62 children in their
      home communities 6-9 months after harvest (baseline). Samples were tested for
      cholinesterase corrected for haemoglobin and ambient temperature. RESULTS:
      Fifteen per cent of children had depression scores ranging from -40% to 190% of
      their baseline levels. Thirty-three per cent of children had depression scores of
      at least 15% and 86% of children were anaemic. CONCLUSION: These results suggest
      that very young children are exposed to potentially harmful and toxic amounts of
      pesticides while working. Further research is needed to assess the actual acute
      and chronic health impacts of such exposures.

PMID- 17439437
TI  - Identifying children with neurological impairment and disability in resource-poor
      countries.
AB  - BACKGROUND: The burden of neurological impairment (NI) in children living in
      resource-poor countries (RPCs) is unknown. This lack of data is caused by
      inappropriate case detection techniques. In RPCs, the most appropriate method
      should be inexpensive, simple, rapid and accurate. This article reviews methods
      used to identify children with NI and disability in RPCs, evaluating their
      effectiveness and suitability. METHODS: A search of relevant articles was
      performed using the National Library of Medicine via PubMed and Medline search
      engines. In addition, bibliographies of reviews were also browsed to identify
      additional articles, particularly those from World Health Organization and United
      Nations sources and from government and unpublished reports. Key phrases used
      included impairment, disability or handicap and the following terms:
      identification, screening, prevalence and developing countries. Studies included
      were those that fulfilled the following criteria; performed in RPCs, presented
      data in detail to allow reanalysis and provided data on cost and validity of the
      methods. RESULTS: Use of the national census, key informants and methods using
      rapid rural appraisal have low sensitivity and are not able to provide adequate
      information on diagnostic categories or risk factors. House-to-house surveys
      using questionnaires have high sensitivities (63-100%) in the detection of
      impairment, but this approach remains relatively expensive and cannot be applied
      to an entire population (e.g. a region or country) and is thus less useful for
      assessing the needs of disability. Furthermore, the sensitivity is decreased in
      the detection of some domains, e.g. cognition. CONCLUSIONS: Most of the
      approaches used for identifying individuals with NI or disability suffer from
      inadequacies, the main ones being low sensitivity and underreporting. To assess
      the burden, nationwide censuses combined with surveys in selected areas of the
      country may be useful. These systems, however, require validation to establish
      their suitability.

PMID- 17439438
TI  - Congenital anomalies in Iran: a cross-sectional study on 1574 cases in the North
      West of country.
AB  - BACKGROUND: At least one congenital anomaly is present in between 1% and 6% of
      all infants throughout the world. The aim of this study was to document some
      epidemiological features of congenital anomalies in the North-West of Iran.
      METHODS: The study cases (n = 1574) comprised all births registered/notified to
      three university-hospitals of Tabriz University of Medical Sciences, Iran, from
      2000 to 2004. RESULTS: Total prevalence of congenital anomalies was 165.5 per 10
      000 births [95% confidence interval (CI): 157-174]. Genito-urinary tract and
      kidney defects, anomalies of nervous system and limb anomalies accounted
      proportionally for more than 65% of anomalies in the region. The total prevalence
      of congenital anomalies in the study area increased from 104.6 per 10 000 births
      in 2000 (95% CI: 90-119) to 170.1 per 10 000 births in 2004 (95% CI: 152-189).
      CONCLUSIONS: It is concluded that the data from this cross-sectional study of
      congenital anomalies in the North-West of Iran may be used as the baseline
      information to establish a population-based registry of birth defects in the area
      for health care and research purposes.

PMID- 17439439
TI  - Validity and reliability of Infant Neurological International Battery for
      detection of gross motor developmental delay in Iran.
AB  - BACKGROUND: Child development screening is important issue for early detection of
      developmental delay and disability. Children in different environment acquire
      developmental abilities at different age. In this paper we report the examination
      of Infant Neurological International Battery (INFANIB) as a screening tool for
      early detection of gross motor developmental delay in Iran. METHODS: In this
      study, we reported the result of a study which was conducted on 6150 consecutive
      4- to 18-month infants who were referred form Karaj Health Network (Tehran
      Province) over a 12-month period. A questionnaire was filled for each child, and
      an evaluation was carried out with INFANIB by occupational therapists. Assessed
      infants had been classified in three categories: normal, transiently abnormal and
      abnormal neuro-development. The transient group infants were divided to normal
      and abnormal group after 3 months' follow-up. The abnormal group was referred to
      developmental centre for neuro-developmental examination. For depicting validity
      of the test, some of the normal, transient and abnormal group was evaluated
      randomly by paediatrician for neuro-developmental exam and for reliability of
      test between paediatrician and occupational therapist 54 infants scored randomly
      by both of them. RESULTS: The INFANIB was valid for normal and abnormal group
      with 90% sensitivity, 83% specificity, 79% positive predictive value and 93%
      negative predictive value (NPV). Also the reliability coefficient between the
      examiners (paediatrician and occupational therapists) was calculated, and the
      intraclass correlation coefficient was 0.90. CONCLUSIONS: Results indicate that
      INFANIB is proposed as an appropriate screening test in developing countries such
      as Iran as a reliable measurement of gross motor developmental delay and short
      time of performing.

PMID- 17439440
TI  - Change and continuity: childbirth and parenting across three generations of women
      in the United Arab Emirates.
AB  - BACKGROUND: The United Arab Emirates (UAE) is a country that has undergone
      remarkable physical, economic and social shifts in its short modern history. And
      while the economic and structural transformations of the society have been well
      documented and publicized, information about the changes and transformations of
      family processes is sparse. This study is one of the first steps towards
      documenting the changes in family processes, namely those related to childbirth
      and parenting, as described by three generations of Emirati women. METHODS:
      Family triads of Grandmothers, Mothers and married Daughters (n = 216) were
      interviewed in local Arabic dialect by Emirati female research assistants. Data
      were analysed using chi square and Analysis of Variance. RESULTS: Generational
      differences were found between the Grandmothers, Mothers and Daughters in: number
      of births, maternal age at first birth, location and type of birth attendant,
      medication during labour and birth, father presence at birth, social support
      following birth, feeding and weaning of infant, and preventive infant health
      care. Changes were not found in the proximity to the mother of the infant during
      sleep. CONCLUSIONS: The age of first birth has risen for Emirati women and the
      birth rate may have dropped. Health care has also significantly improved. These
      results are discussed in relation to government initiatives and physical and
      social change within the UAE and the Middle East.

PMID- 17439441
TI  - Internet addiction among Chinese adolescents: prevalence and psychological
      features.
AB  - BACKGROUND: To investigate the prevalence of Internet addiction among Chinese
      adolescents and to explore the psychological features associated with Internet
      addiction. METHODS: A total of 2620 high school students from four high schools
      in Changsha City were surveyed using Diagnostic Questionnaire for Internet
      Addiction (YDQ), Eysenck Personality Questionnaire (the edition for children,
      EPQ), Time Management Disposition Scale (TMDS) and Strengths and Difficulties
      Questionnaire (SDQ). The mean age of whole sample was 15.19 years (ranging from
      12 years to 18 years). According to the modified YDQ criteria by Beard, 64
      students who were diagnosed as Internet addiction (the mean age: 14.59 years) and
      64 who were diagnosed as being normal in Internet usage (the mean age: 14.81
      years) were included in a case-control study. RESULTS: The rate of Internet use
      among the surveyed adolescents was 88%, among which the incidence rate of
      Internet addiction was 2.4%. The Internet addiction group had significantly
      higher scores on the EPQ subscales of neuroticism, psychoticism, and lie than the
      control group (P < 0.05). The Internet addiction group scored lower than the
      control group on the TMDS subscales of sense of control over time, sense of value
      of time, and sense of time efficacy (P < 0.05). Compared with the control group,
      the Internet addiction group had also significantly higher scores on the SDQ
      subscales of emotional symptoms, conduct problems, hyperactivity, total
      difficulties and lower scores on the subscale of prosocial behaviours (P < 0.05).
      CONCLUSIONS: The present study suggests that Internet addiction is not rare among
      Chinese adolescents. In addition, adolescents with Internet addiction possess
      different psychological features when compared with those who use the Internet
      less frequently.

PMID- 17439442
TI  - Learning from mothers: how myths, policies and practices affect the detection of
      subtle developmental problems in children.
AB  - BACKGROUND: Recent research has revealed increasing concerns over the number of
      children entering school with unidentified developmental problems, even though
      there are ostensibly comprehensive health services available for mothers and
      their children in the pre-school years. Recognizing that early detection and
      early intervention reduce the likelihood of long-term health and educational
      problems, it is important to understand why so many children are not detected
      with developmental problems in their pre-school years. METHODS: This doctoral
      study utilized the knowledge and experience of mothers to draw attention to
      reasons why children with subtle developmental problems are not identified until
      school age. A qualitative methodology utilized a synthesis of interpretive
      biography and literary folkloristics as a method of collecting, reading and
      interpreting personal stories. Three literary theories, arising, respectively,
      from the tenets of semiotics, neoMarxism and post-structuralism, were used to
      critically deconstruct the mothers' stories. RESULTS: The findings highlight a
      number of factors that influence the interaction between mothers, health
      professionals and members of the community, and how these interactions impact on
      the early detection of children's developmental problems. The findings illustrate
      the influence of societal myths on how mothers and health professionals view
      their roles, and on how they think about and respond to the child's problem. They
      also confirm the value placed on professional knowledge and the role it plays in
      communications between mothers and health professionals. Finally, they draw
      attention to how competing arguments about diagnosis and labelling delay
      identification and access to intervention programmes for children. CONCLUSION:
      Health professionals working with mothers and young children should be aware of
      how their values, beliefs and communication styles affect their professional
      practice, especially when interacting with mothers who raise concerns about their
      children. State policies that limit access to early intervention programmes
      should also be reconsidered so that young children are not excluded from
      assistance.

PMID- 17439443
TI  - Can we count them? Scoping data sources on disabled children and their households
      in the UK.

PMID- 17439444
TI  - Why do we need a diagnosis? A qualitative study of parents' experiences, coping
      and needs, when the newborn child is severely disabled.
AB  - BACKGROUND: Communication with parents who are realizing their child is severely
      disabled is a difficult task for professionals. Parents are experiencing great
      emotional stress during the diagnostic process and dissatisfaction with
      disclosure is widespread. The aim of this study was to investigate parents'
      reactions when realizing their child's disability, the impact of the diagnosis
      and parents' ways of coping. METHODS: This was a qualitative, longitudinal study,
      using in-depth interviews with 16 parents of a physically and mentally disabled
      child who had recently been diagnosed as such. Children's age at inclusion ranged
      from 1 to 27 months. Half of the children had an unknown diagnosis. Data were
      analysed using the Grounded Theory method. RESULTS: were validated and approved
      by the interviewed parents. RESULTS: The certainty of the diagnosis was central
      for parents' experiences. First, the emotional reaction of the parents is highly
      influenced by the diagnostic process. Second, parents needed possibilities for
      taking action, and third they found difficulty in coping with an uncertain
      future. These three themes all related to the meaning that parents ascribed to
      the stating of a diagnosis. Parents' needs in relation to communication were
      identified as equality in co-operation with doctors, an empathic professional
      approach, and the child being seen with possibilities despite his or her
      disabilities. CONCLUSIONS: Parents' process of realization was related to the
      diagnostic process, and information and communication should be individualized
      accordingly. Parents wanted to co-operate and they needed possibilities for
      active coping with their situation.

PMID- 17439445
TI  - Social perception of the development of disabled children.
AB  - BACKGROUND: This experiment extends our study of perception of the disabled from
      the realm of personality into child development to determine if our results,
      which reveal prejudice against disabled adults, apply to perceptions of a
      toddler's development. METHODS: Participants watched a video of either a disabled
      or a non-disabled toddler in sessions conducted by either a disabled or a non
      disabled experimenter. Participants rated the target using the Achenbach
      Caregiver-Teacher Report Form for ages 1.5-5 years twice: first, each participant
      imagined being the caregiver of the toddler at age 4 years (self-rating), and
      then the participant envisioned how a typical childcare provider would rate the
      target (other-rating). RESULTS: Data revealed an interaction between the
      experimenter's disability and the source of ratings. For the disabled
      experimenter, participants thought that "others" would perceive more behavioural
      problems than they themselves do. For the non-disabled experimenter, participants
      rated the disabled target more pessimistically in both the self- and other
      ratings. CONCLUSION: As we found in our first study of disabled adults, our
      current results reveal subtle prejudice against disabled children.

PMID- 17439446
TI  - 22q11.2 deletion syndrome: behaviour problems of infants and parental stress.
AB  - BACKGROUND: 22q11.2 deletion syndrome (22q11.2 DS) can be associated with a
      variety of somatic symptoms, developmental delays and psychiatric disorders. At
      present, there is little information on early behaviour problems, and nothing is
      known about parental stress and possible relations between these factors.
      Therefore, the aim of this study was to investigate behaviour problems of infants
      with 22q11.2 DS, and their primary caregivers' stress. METHODS: Parents of
      infants with 22q11.2 DS known to the German 22q11.2 deletion syndrome foundation
      were anonymously asked to fill out several questionnaires, e.g. the Child
      Behavior Checklist (CBCL) 1.5-5. RESULTS: The primary caregivers of 22/30
      children [12 boys and 10 girls aged 1 year 8 months to 3 years 11 months (mean
      age: 2 years 9 months)] sent back filled-out questionnaires. Seventeen out of 21
      children showed motor, and 15/21 language delay. Five out of 21 children were
      rated as clinical on at least one CBCL 1.5-5 scale. The patients' age was
      correlated with anxiety problems, and girls had significantly more sleep problems
      than boys. Compared with the general population, the primary caregivers did not
      experience higher levels of strain, and compared with parents of mentally and/or
      physically handicapped children, their parental stress was significantly lower.
      Parental stress and strain were correlated to a variety of child behaviour
      problems, e.g. externalizing and anxious/depressed behaviour. CONCLUSIONS:
      Longitudinal studies are required to show whether behaviour problems and parental
      stress worsen when 22q11.2 DS patients grow older.

PMID- 17439447
TI  - Early identification: are speech/language-impaired toddlers at increased risk for
      Developmental Coordination Disorder?
AB  - BACKGROUND: Developmental Coordination Disorder (DCD) is a movement skill
      disorder which impacts upon a child's ability to perform age-appropriate self
      care and academic tasks. DCD is commonly comorbid with speech/language learning
      disabilities. AIM: The present study was conducted to determine whether children
      who had been identified with speech/language delays as toddlers demonstrated
      characteristics of DCD and/or speech/language problems at kindergarten age.
      RESULTS: Speech/language and motor assessments who were followed up at 63-80
      months of age. Of the 40 children, 18 showed evidence of significant motor
      impairment and two-thirds of these met diagnostic criteria for DCD at follow-up.
      Twelve children were identified as having persistent speech/language problems
      and, of these, nine presented with significant motor co-ordination difficulties.
      Parental report of gross motor and fine motor problems at follow-up correlated
      highly with actual motor impairment scores. CONCLUSIONS: Young children who are
      in early intervention programmes for speech/language delays may have significant
      co-ordination difficulties that will become more evident at kindergarten age when
      motor deficits begin to impact self-care and academic tasks. Clinical
      implications for early recognition of motor issues by speech/language
      pathologists and the potential use of parental reporting tools are addressed.

PMID- 17439448
TI  - Paediatricians' attitudes about discussing maternal depression during a
      paediatric primary care visit.
AB  - OBJECTIVES: To assess paediatricians' beliefs about discussing maternal
      depressive symptoms during a paediatric visit, and methods paediatricians use to
      identify mothers with depressive symptoms. METHODS: In-depth telephone interviews
      were conducted with 23 primary care paediatricians from a practice-based research
      network. We asked a series of previously developed questions about discussing
      maternal depressive symptoms during a paediatric visit; methods used to identify
      mothers at risk; barriers encountered, and potential strategies to improve
      recognition and treatment of maternal depression. Interviews were audiotaped and
      transcribed. Data were codified and analysed using standard qualitative data
      techniques. RESULTS: All paediatricians agreed that it is appropriate to ask
      mothers about their own health during a well-child visit, because a mother's well
      being affects her children. Paediatricians relied on observational cues to
      identify a mother with depressive symptoms, especially mother-child interactions.
      Few used direct questions or a checklist. Almost all paediatricians felt that
      lack of time was the barrier most often faced in addressing maternal depression.
      Lack of training, inadequate knowledge of resources and distractions encountered
      in the primary care setting were additional barriers cited. One-third of
      paediatricians acknowledged the fear of judgement and stigma that a mother may
      face when discussing maternal stresses. Paediatricians desired better ability to
      refer mothers to social workers for help. CONCLUSIONS: Observational cues are
      used more often than direct questions or screening tools to identify mothers at
      risk of depression. This may under-identify mothers at risk. Paediatricians
      prefer to rely on other professionals, particularly social services, to address
      maternal depression, yet mothers may be hesitant or ambivalent about such
      assistance because of fear of judgement. Paediatricians, in fact, may be the
      professional mothers most want to communicate with. Thus, appreciation of
      mothers' perspectives, empathetic communication skills and knowledge of community
      resources can enhance paediatricians' abilities to assist mothers at risk for
      depression.

PMID- 17439449
TI  - Career choices for paediatrics: national surveys of graduates of 1974-2002 from
      UK medical schools.
AB  - BACKGROUND: Knowledge of UK doctors' career intentions and pathways is essential
      for understanding future workforce requirements. The aim of this study was to
      report career choices for and career progression in paediatrics in the UK.
      METHODS: Postal questionnaire surveys of qualifiers from all UK medical schools
      in nine qualification years since 1974. RESULTS: In total, 74% (24 621/33 412)
      and 73% (20 720/28 459) of doctors responded at 1 and 3 years after graduation.
      Choices for paediatrics 1 year after qualifying fell from 7.8% of 1974 graduates
      to 5.0% of 1983 graduates, increased to 7.2% of 1993 graduates, and since the
      level has remained fairly constant. Approximately twice the percentage of women
      graduates than men graduates indicated a long-term career choice for paediatrics.
      A total of 44% of those who chose paediatrics 1 year after graduation were
      working in it 10 years after qualifying. Experience of the subject as a student,
      and enthusiasm/commitment: what I really want to do, affected long-term career
      choices more for paediatrics than for other medical careers. CONCLUSIONS: The
      proportion of junior doctors wishing to become paediatricians has not changed
      much during the last 30 years. The planned increase in the number of medical
      school graduates is necessary to increase the number of UK-trained consultant
      paediatricians. Medical students who experience enthusiastic and stimulating
      training in paediatrics may be more likely to become paediatricians.

PMID- 17439459
TI  - Role of larval host plants in the climate-driven range expansion of the butterfly
      Polygonia c-album.
AB  - 1. Some species have expanded their ranges during recent climate warming and the
      availability of breeding habitat and species' dispersal ability are two important
      factors determining expansions. The exploitation of a wide range of larval host
      plants should increase an herbivorous insect species' ability to track climate by
      increasing habitat availability. Therefore we investigated whether the
      performance of a species on different host plants changed towards its range
      boundary, and under warmer temperatures. 2. We studied the polyphagous butterfly
      Polygonia c-album, which is currently expanding its range in Britain and
      apparently has altered its host plant preference from Humulus lupulus to include
      other hosts (particularly Ulmus glabra and Urtica dioica). We investigated insect
      performance (development time, larval growth rate, adult size, survival) and
      adult flight morphology on these host plants under four rearing temperatures (18
      28.5 degrees C) in populations from core and range margin sites. 3. In general,
      differences between core and margin populations were small compared with effects
      of rearing temperature and host plant. In terms of insect performance, host
      plants were generally ranked U. glabra > or = U. dioica > H. lupulus at all
      temperatures. Adult P. c-album can either enter diapause or develop directly and
      higher temperatures resulted in more directly developing adults, but lower
      survival rates (particularly on the original host H. lupulus) and smaller adult
      size. 4. Adult flight morphology of wild-caught individuals from range margin
      populations appeared to be related to increased dispersal potential relative to
      core populations. However, there was no difference in laboratory reared
      individuals, and conflicting results were obtained for different measures of
      flight morphology in relation to larval host plant and temperature effects,
      making conclusions about dispersal potential difficult. 5. Current range
      expansion of P. c-album is associated with the exploitation of more widespread
      host plants on which performance is improved. This study demonstrates how
      polyphagy may enhance the ability of species to track climate change. Our
      findings suggest that observed differences in climate-driven range shifts of
      generalist vs. specialist species may increase in the future and are likely to
      lead to greatly altered community composition.

PMID- 17439460
TI  - Regional climate modulates the canopy mosaic of favourable and risky
      microclimates for insects.
AB  - 1. One major gap in our ability to predict the impacts of climate change is a
      quantitative analysis of temperatures experienced by organisms under natural
      conditions. We developed a framework to describe and quantify the impacts of
      local climate on the mosaic of microclimates and physiological states of insects
      within tree canopies. This approach was applied to a leaf mining moth feeding on
      apple leaf tissues. 2. Canopy geometry was explicitly considered by mapping the
      3D position and orientation of more than 26 000 leaves in an apple tree. Four
      published models for canopy radiation interception, energy budget of leaves and
      mines, body temperature and developmental rate of the leaf miner were integrated.
      Model predictions were compared with actual microclimate temperatures. The
      biophysical model accurately predicted temperature within mines at different
      positions within the tree crown. 3. Field temperature measurements indicated that
      leaf and mine temperature patterns differ according to the regional climatic
      conditions (cloudy or sunny) and depending on their location within the canopy.
      Mines in the sun can be warmer than those in the shade by several degrees and the
      heterogeneity of mine temperature was incremented by 120%, compared with that of
      leaf temperature. 4. The integrated model was used to explore the impact of both
      warm and exceptionally hot climatic conditions recorded during a heat wave on the
      microclimate heterogeneity at canopy scale. During warm conditions, larvae in
      sunlight-exposed mines experienced nearly optimal growth conditions compared with
      those within shaded mines. The developmental rate was increased by almost 50% in
      the sunny microhabitat compared with the shaded location. Larvae, however,
      experienced optimal temperatures for their development inside shaded mines during
      extreme climatic conditions, whereas larvae in exposed mines were overheating,
      leading to major risks of mortality. 5. Tree canopies act as both magnifiers and
      reducers of the climatic regime experienced in open air outside canopies.
      Favourable and risky spots within the canopy do change as a function of the
      climatic conditions at the regional scale. The shifting nature of the mosaic of
      suitable and risky habitats may explain the observed uniform distribution of leaf
      miners within tree canopies.

PMID- 17439461
TI  - Ontogenetic colour change and the evolution of aposematism: a case study in panic
      moth caterpillars.
AB  - 1. Aposematism is a widely used antipredator strategy in which an organism
      possesses both warning coloration and unprofitable characters. Theoretical
      evidence suggests that aposematic colour should develop when high opportunity
      costs imposed by crypsis force an organism to engage in conspicuous behaviours.
      Hence, it is expected that ontogenetic colour change (OCC) in larval insects
      should include aposematism when foraging needs compel behavioural modifications
      that preclude a continued state of crypsis. 2. To test this idea, I first
      investigated whether OCC in caterpillars of the panic moth Saucrobotys futilalis
      was indicative of a switch from cryptic to aposematic coloration. I then examined
      the context of panic moth OCC as it related to foraging patterns and behavioural
      conspicuousness. 3. Early Saucrobotys instars are a cryptic green, but later
      instars become progressively more orange and develop black spots. Early instar
      larvae forage cryptically on the inner parenchyma of silked-together host plant
      leaves to avoid predation, but are rapidly forced to engage in conspicuous
      foraging behaviours as they outgrow the resources afforded by their shelters.
      Both coloration and behaviour reach maximal conspicuousness in final instar
      larvae. 4. As predicted, OCC encompassed a change from crypsis to aposematism in
      Saucrobotys. Aposematic function was demonstrated by changes in both antipredator
      behaviour patterns and effectiveness of predator deterrence in early and late
      instars. Moreover, increased opportunity costs of crypsis and behavioural
      conspicuousness coincided with the onset of aposematic coloration. 5. This
      pattern of OCC suggests that aposematic coloration in Saucrobotys develops as a
      response to constraints imposed by crypsis. Moreover, my study illustrates the
      importance of the study of ontogenetic patterns in determining how behaviour,
      morphology, and predator responses interact to influence the initial evolution of
      phenomena such as aposematism.

PMID- 17439462
TI  - Evaluation of reproductive costs for Weddell seals in Erebus Bay, Antarctica.
AB  - 1. Organisms balance current reproduction against future survival and
      reproduction, which results in life-history trade-offs. These trade-offs are also
      known as reproductive costs and may represent significant factors shaping life
      history strategy for many species. 2. Using multistate mark-resight models and 26
      years of mark-resight data (1979-2004), we estimated the costs of reproduction to
      survival and reproductive probabilities for Weddell seals in Erebus Bay,
      Antarctica and evaluated whether this species either conformed to the 'prudent
      parent' reproductive strategy predicted by life-history theory for long-lived
      mammals or alternatively, incurred costs to survival in order to reproduce in a
      variable environment (flexible-strategy hypothesis). 3. Results strongly
      supported the presence of reproductive costs to survival (mean annual survival
      probability was 0.91 for breeders vs. 0.94 for nonbreeders), a notable difference
      for a long-lived mammal, demonstrating that investment in reproduction does
      result in a cost to survival for Weddell seals, contrary to the prudent parent
      hypothesis. 4. Reproductive costs to subsequent reproductive probabilities were
      also present for first-time breeders (mean probability of breeding the next year
      was 31.3% lower for first-time breeders than for experienced breeders), thus
      supporting our prediction of the influence of breeding experience. 5. We detected
      substantial annual variation in survival and breeding probabilities. Breeding
      probabilities were negatively influenced by summer sea-ice extent, whereas weak
      evidence suggested that survival probabilities were affected more by winter sea
      ice extent, and the direction of this effect was negative. However, a model with
      annual variation unrelated to any of our climate or sea-ice covariates performed
      best, indicating that further study will be needed to determine the appropriate
      mechanism or combination of mechanisms underlying this annual variation.

PMID- 17439463
TI  - Age-specific variation in reproduction is largely explained by the timing of
      territory establishment in the New Zealand stitchbird Notiomystis cincta.
AB  - 1. Using data from 327 nests over a consecutive 8-year period we examined age
      specific variation in reproduction in a population of stitchbirds (or hihi)
      Notiomystis cincta and related how differences in reproductive performance were
      linked to the timing of territory establishment and breeding. 2. Across the
      population all reproductive parameters showed a quadratic relationship with an
      increase mainly between the first and second breeding season and a decline after
      the fourth year. A longitudinal analysis showed evidence of senescence by the
      sixth year in the numbers of chicks fledged and recruited. 3. Reproductive
      increases between years 1 and 2 were the result of poor-quality females dying
      after their first breeding season (differential selection hypothesis) in
      combination with surviving females showing improvements in reproduction in their
      second year (individual improvement/constraint hypothesis). 4. There was no
      effect of mate experience or territory quality on improvements in breeding
      between years. 5. The key variable influencing reproductive output was the timing
      of breeding. Birds that started laying earlier were more likely to lay multiple
      clutches in any given season. This was the main difference between first-year and
      older birds; generally first-year birds initiated egg laying later and
      consequently laid fewer clutches. 6. Approximately half of all first-year birds
      did not establish their territory until after the breeding season had begun. This
      delay in territory establishment resulted in these birds delaying breeding, which
      resulted in them having a lower reproductive output relative to all other birds.
      First-year birds that managed to establish their territory before breeding
      commenced, had similar rates of reproduction as older birds. 7. There was a
      positive relationship between the timing of territory establishment during a
      female's first year and her hatching date in the previous breeding season. We
      hypothesize that this was because late-hatched females were less able to
      effectively compete for territories against earlier-hatched members of their
      cohort, and this delayed their establishment and breeding in their first year.
      Thus, this social constraint is likely to be a major factor driving age-specific
      reproductive variation in this population.

PMID- 17439464
TI  - Effects of breeding success, mate fidelity and senescence on breeding dispersal
      of male and female blue-footed boobies.
AB  - 1. Understanding the effects of individual and population factors on variation in
      breeding dispersal (the movement of individuals between successive breeding
      sites) is key to identifying the strategies behind breeders' movements. Dispersal
      is often influenced by multiple factors and these can be confounded with each
      other. We used 13 years of data on the locations, mates, breeding success and
      ages of individuals to tease apart the factors influencing breeding dispersal in
      a colonially breeding long-lived seabird, the blue-footed booby Sula nebouxii. 2.
      Breeding dispersal varied among and within years. Males dispersed further in
      years of higher population density, and late breeding males and females dispersed
      further than early breeders. This temporal variation related to changes in
      competition for territory was taken into account in all tests of individual
      factors influencing breeding dispersal. 3. Individuals that retained their mates
      from the previous year dispersed shorter distances than those that changed their
      mates. 4. The effect of previous breeding success depended on mate fidelity.
      Unsuccessful breeding induced greater dispersal in birds that changed their mates
      but not in birds that retained their mates, indicating that breeders who change
      mates may take their own previous breeding experience into account during habitat
      selection. Faithful individuals may have to stay close to their previous sites to
      encounter their mates. 5. Male divorcees dispersed over shorter distances than
      their former mates, possibly because males contribute more than females to
      establishing territories. 6. Dispersal of males and females declined with
      increasing age over the first 10-11 years of life, then increased in old age,
      possibly due to senescent decay in the ability to compete for mates and
      territories.

PMID- 17439465
TI  - Inferring population trends for the world's largest fish from mark-recapture
      estimates of survival.
AB  - 1. Precise estimates of demographic rates are key components of population models
      used to predict the effects of stochastic environmental processes, harvest
      scenarios and extinction probability. 2. We used a 12-year photographic
      identification library of whale sharks from Ningaloo Reef, Western Australia to
      construct Cormack-Jolly-Seber (CJS) model estimates of survival within a capture
      mark-recapture (CMR) framework. Estimated survival rates, population structure
      and assumptions regarding age at maturity, longevity and reproduction frequency
      were combined in a series of age-classified Leslie matrices to infer the
      potential trajectory of the population. 3. Using data from 111 individuals, there
      was evidence for time variation in apparent survival (phi) and recapture
      probability (p). The null model gave a phi of 0.825 (95% CI: 0.727-0.893) and p =
      0.184 (95% CI: 0.121-0.271). The model-averaged annual phi ranged from 0.737 to
      0.890. There was little evidence for a sex effect on survival. 4. Using
      standardized total length as a covariate in the CMR models indicated a size bias
      in phi. Ignoring the effects of time, a 5-m shark has a phi = 0.59 and a 9 m
      shark has phi = 0.81. 5. Of the 16 model combinations considered, 10 (63%)
      indicated a decreasing population (lambda < 1). For models based on age at first
      reproduction (alpha) of 13 years, the mean age of reproducing females at the
      stable age distribution (A) ranged from 15 to 23 years, which increased to 29-37
      years when alpha was assumed to be 25. 6. All model scenarios had higher total
      elasticities for non-reproductive female survival [E(s(nr))] compared to those
      for reproductive female survival [E(s(r))]. 7. Assuming relatively slow, but
      biologically realistic, vital rates (alpha = 25 and biennial reproduction) and
      size-biased survival probabilities, our results suggest that the Ningaloo Reef
      population of whale sharks is declining, although more reproductive data are
      clearly needed to confirm this conclusion. Combining relatively precise survival
      estimates from CMR studies with realistic assumptions of other vital rates
      provides a useful heuristic framework for determining the vulnerability of large
      oceanic predators for which few direct data exist.

PMID- 17439466
TI  - Sex differences in grey seal diet reflect seasonal variation in foraging
      behaviour and reproductive expenditure: evidence from quantitative fatty acid
      signature analysis.
AB  - 1. Intraspecific variation in diet can be an important component of a species
      niche breadth. We tested the hypothesis that sex differences in seasonal foraging
      behaviour and energy storage of sexually size dimorphic grey seals Halichoerus
      grypus (Fabrisius 1971) are reflected in differences in the diet and niche
      breadth. Diet composition was estimated for 496 adult (226 males, 270 females)
      and 91 juvenile (46 males/45 females; all 6 months old) grey seals sampled
      between 1993 and 2000 using quantitative fatty acid signature analysis. Niche
      breadth and overlap were estimated using the Shannon-Weaver diversity index (H')
      and the Morisita-Horn index (C(H)), respectively. 2. Sand lance Ammodytes dubius
      (Reinhardt 1837) and redfish Sebastes sp. (Cuvier 1829) accounted for a high
      proportion of the diet in both sexes and age groups. However, the diets of adult
      males were significantly more diverse across all seasons (H': males 0.36 +/-
      0.007 vs. females 0.28 +/- 0.007) and less energy dense in spring (male 5.3 +/-
      0.07 kJ g(-1) vs. females 5.6 +/- 0.09 kJ g(-1)) than those of adult females. 3.
      Season and sex explained most of the observed variation in adult diets, but there
      were significant sex-season interactions. These differences were most evident
      during the post-breeding (spring) foraging period when energy acquisition is
      important to female recovery of nutrient stores needed to support pregnancy.
      Females selected fewer and higher quality prey species in spring than males. 4.
      There were no sex differences in the diets of juvenile grey seals. Although many
      of the species overlapped with those eaten by adults, juvenile niche breadth (H':
      0.41 +/- 0.014, n = 91) was significantly broader than that of adults (H': 0.30
      +/- 0.011, n = 115). Juvenile diets were also of lower energy density (5.3 +/-
      0.04 kJ g(-1)) than those of adults (5.6 +/- 0.09 kJ g(-1)), suggesting less
      selectivity in these young and relatively naive predators. 5. Sex-specific
      seasonal changes in diet correspond to seasonal changes in diving behaviour and
      rate of body energy accumulation of adult males and females. Sex-specific
      reproductive requirements appear to be a primary factor generating the
      intraspecific variation in the seasonal foraging ecology of this large marine
      carnivore. However, sex differences in the breadth and energy content of diets
      also suggest the influence of body-size dimorphism as a factor shaping the diet
      of this species.

PMID- 17439467
TI  - Shorebird predation of horseshoe crab eggs in Delaware Bay: species contrasts and
      availability constraints.
AB  - 1. Functional responses -- the relationship between resource intake rate and
      resource abundance -- are widely used in explaining predator-prey interactions
      yet many studies indicate that resource availability is crucial in dictating
      intake rates. 2. For time-stressed migrant birds refuelling at passage sites,
      correct decisions concerning patch use are crucial as they determine fattening
      rates and an individual's future survival and reproduction. Measuring
      availability alongside abundance is essential if spatial and temporal patterns of
      foraging are to be explained. 3. A suite of shorebird species stage in Delaware
      Bay where they consume horseshoe crab Limulus polyphemus eggs. Several factors
      including spawning activity and weather give rise to marked spatial and temporal
      variation in the abundance and availability of eggs. We undertook field
      experiments to determine and contrast the intake rates of shorebird species
      pecking for surface and probing for buried eggs. 4. Whether eggs were presented
      on the sand surface or buried, we demonstrate strong aggregative responses and
      rapid depletion (up to 80%). Depletion was greater at deeper depths when more
      eggs were present. No consistent give-up densities were found. Type II functional
      responses were found for surface eggs and buried eggs, with peck success twice as
      high in the former. Maximum intake rates of surface eggs were up to 83% higher
      than those of buried eggs. 5. Caution is needed when applying functional
      responses predicted on the basis of morphology. Our expectation of a positive
      relationship between body size and intake rate was not fully supported. The
      smallest species, semipalmated sandpiper, had the lowest intake rate but the
      largest species, red knot, achieved only the same intake rate as the mid-sized
      dunlin. 6. These functional responses indicate that probing is rarely more
      profitable than pecking. Currently, few beaches provide egg densities sufficient
      for efficient probing. Areas where eggs are deposited on the sand surface are
      critical for successful foraging and ongoing migration. This may be especially
      true for red knot, which have higher energetic demands owing to their larger body
      size yet appear to have depressed intake rates because they consume smaller prey
      than their body size should permit.

PMID- 17439468
TI  - Agriculture, fertilizers and life history of a coastal seabird.
AB  - 1. Leakage of fertilizers from farmland has affected levels of nitrogen and
      phosphorus in many coastal areas, reducing limitation of primary productivity
      with consequences for timing and magnitude of the annual peak in phytoplankton
      and zooplankton. Such changes in nutrient availability may have affected temporal
      patterns of abundance of marine invertebrates and vertebrates that are the main
      prey of seabirds. 2. We investigated the extent to which changes in the use of
      fertilizers by farmers affected timing of breeding, clutch size, recruitment and
      longevity of a coastal seabird, the Arctic tern Sterna paradisaea Pont., in
      Denmark. 3. Timing of breeding advanced with the increase in use of fertilizers,
      with an effect as a consequence of a phenotypic response of individuals exposed
      to different levels of fertilizers. 4. Annual mean clutch size increased with the
      amount of fertilizer. While individual Arctic terns increased their clutch size
      with fertilizer level, there was no evidence of individual Arctic terns in
      different years changing their clutch size in response to changes in fertilizer
      use. 5. Annual recruitment rate, estimated as the proportion of young that were
      subsequently recovered as adults, was related to fertilizer use. 6. Mean
      longevity, estimated as the maximum age of adult individuals, decreased in
      response to fertilizer use. 7. These findings provide evidence of fertilizer use
      in agriculture having significant indirect effects on timing of reproduction,
      clutch size, recruitment and longevity of a seabird.

PMID- 17439469
TI  - Significance of diet type and diet quality for ecological diversity of African
      ungulates.
AB  - 1. We test two nutritional hypotheses for the ecological diversity of ungulates,
      the browser/grazer (diet type) and diet quality models, among free-ranging
      herbivores in a South African savanna, the Kruger National Park. Tests are based
      on assessment of relationships between diet type and diet quality with body mass
      and hypsodonty, two morphological features that have been associated with both
      elements. 2. We use stable carbon isotope ratios of faeces to reconstruct diet in
      terms of proportions of C(3) plants (browse) and C(4) plants (grass) consumed by
      different species in different seasons. These data are combined with proxies for
      diet quality (per cent nitrogen, neutral detergent fibre, acid detergent fibre,
      and acid detergent lignin) from faeces to track changes in diet quality. 3. Two
      statistical approaches are used in model selection, i.e. tests of significant
      correlations based on linear regression analyses, and an information-theory
      approach (Akaike's Information Criterion) providing insight into strength of
      evidence for models. 4. Results of both methods show that, contrary to many
      predictions, body mass and diet type are not related, but these data confirm
      predictions that diet quality decreases with increasing body size, especially
      during the dry season. Hypsodonty, as expected, varies with diet type, increasing
      with increased grass intake. 5. These findings support both a diet type and diet
      quality model, implying some degree of exclusivity. We propose that congruence
      between models may be achieved through addition of diet quality proxies not
      included here, because hypsodonty is more likely a reflection of the abrasive
      properties of consumed foods, i.e. related to food quality, rather than food
      type. This implies that adaptation to diets of varying quality, through changes
      in body size and dental features, has been the primary mechanism for
      diversification in ungulates. 6. Our interpretation contrasts with several recent
      studies advocating diet type as the primary factor, exemplifying that further
      reconciliation between the two models is needed. We discuss the implications of
      this study for future approaches to achieve a more cohesive understanding of the
      evolutionary outcomes of herbivore nutrition.

PMID- 17439470
TI  - The influence of trophic status and large-scale climatic change on the structure
      of fish communities in Perialpine lakes.
AB  - 1. A recurrent question in ecology is the influence of environmental factors,
      particularly nutrients and climatic variables, on community structure and
      functioning, and their interaction with internal community processes (e.g.
      competition). 2. Perialpine lakes have been subject to two main kinds of human
      induced changes over the last 50 years: eutrophication-reoligotrophication,
      represented by lake-specific changes in total phosphorus concentration (TP), and
      long-term global climatic change, captured by average winter temperature (AWT).
      3. Changes in fish communities (abundance of seven species from fishery data) in
      11 Perialpine lakes during 31 years (1970-2000) were investigated in relation to
      variation in TP and AWT using models incorporating the effects of fish maturation
      age, and potentially discriminating effects on adult survival and recruitment. 4.
      We show that phosphorus concentration affects fish abundance in species-specific
      ways. These effects are mediated by recruitment rather than by adult survival.
      Phosphorus effects are probably modulated by interspecific interactions, as
      increasing TP enhances total community biomass, which in turn is either
      positively or negatively associated with species abundance depending on species
      position in trophic chains. 5. Climatic change has very little effect on fish
      abundances, which is not consistent with the prediction of larger changes in
      species near their southern distribution boundary. 6. We propose several
      hypotheses to account for those findings, and place our study in the wider
      framework of community ecology.

PMID- 17439471
TI  - Intra- and interspecific density-dependent dispersal in an aquatic prey-predator
      system.
AB  - 1. Dispersal intensity is a key process for the persistence of prey-predator
      metacommunities. Consequently, knowledge of the ecological mechanisms of
      dispersal is fundamental to understanding the dynamics of these communities.
      Dispersal is often considered to occur at a constant per capita rate; however,
      some experiments demonstrated that dispersal may be a function of local species
      density. 2. Here we use aquatic experimental microcosms under controlled
      conditions to explore intra- and interspecific density-dependent dispersal in two
      protists, a prey Tetrahymena pyriformis and its predator Dileptus sp. 3. We
      observed intraspecific density-dependent dispersal for the prey and interspecific
      density-dependent dispersal for both the prey and the predator. Decreased prey
      density lead to an increase in predator dispersal, while prey dispersal increased
      with predator density. 4. Additional experiments suggest that the prey is able to
      detect its predator through chemical cues and to modify its dispersal behaviour
      accordingly. 5. Density-dependent dispersal suggests that regional processes
      depend on local community dynamics. We discuss the potential consequences of
      density-dependent dispersal on metacommunity dynamics and stability.

PMID- 17439472
TI  - Body size, competitive interactions, and the local distribution of Triturus
      newts.
AB  - 1. Pairs of European Triturus newt species of similar size tend not to co-occur
      syntopically, suggesting that similarity in body size is associated with
      competitive interactions that prevent coexistence. I tested this hypothesis with
      an experiment involving larvae of four species in 675-L artificial ponds. 2.
      There were strong interactions between most species pairs. Even the small T.
      helveticus had a clear impact on the larger T. alpestris. Pairs of species with
      different body sizes did not interact less strongly. 3. A standard increase in
      competitor biomass (c. 2 g mass at metamorphosis) caused 42% lower expected
      survival from hatching to 1 year of age, regardless of whether the species were
      of similar or different size. In most cases this resulted from delayed
      metamorphosis, reduced size at emergence, and slightly lower larval survival. 4.
      A standard increase in competitor density (0.74 individuals m(-2)) caused a
      greater reduction in expected 1-year survival when the competitor was larger (18%
      decline) than when both species were of similar size (6% decline), primarily
      because the very large T. cristatus consumed the smallest species. 5. These
      findings suggest that species interactions during the larval stage cannot explain
      distribution patterns of same- and different-sized Triturus.

PMID- 17439473
TI  - Changes in landscape composition influence the decline of a threatened woodland
      caribou population.
AB  - 1. Large-scale habitat loss is frequently identified with loss of biodiversity,
      but examples of the direct effect of habitat alterations on changes in vital
      rates remain rare. Quantifying and understanding the relationship between habitat
      composition and changes in vital rates, however, is essential for the development
      of effective conservation strategies. 2. It has been suggested that the decline
      of woodland caribou Rangifer tarandus caribou populations in North America is
      precipitated by timber harvesting that creates landscapes of early seral forests.
      Such habitat changes have altered the predator-prey system resulting in
      asymmetric predation, where predators are maintained by alternative prey (i.e.
      apparent competition). However, a direct link between habitat condition and
      caribou population declines has not been documented. 3. We estimated survival
      probabilities for the threatened arboreal lichen-feeding ecotype of woodland
      caribou in British Columbia, Canada, at two different spatial scales. At the
      broader scale, observed variation in adult female survival rates among 10
      distinct populations (range = 0.67-0.93) was best explained by variation in the
      amount of early seral stands within population ranges and population density. At
      the finer scale, home ranges of caribou killed by predators had lower proportions
      of old forest and more mid-aged forest as compared with multi-annual home ranges
      where caribou were alive. 4. These results are consistent with predictions from
      the apparent competition hypothesis and quantify direct fitness consequences for
      caribou following habitat alterations. We conclude that apparent competition can
      cause rapid population declines and even extinction where changes in species
      composition occur following large scale habitat change.

PMID- 17439474
TI  - Army ants in four forests: geographic variation in raid rates and species
      composition.
AB  - 1. The New World army ants are top predators in the litter of tropical forest,
      but no comprehensive studies exist on variation in assemblage-wide activity and
      species composition. We used standardized protocols to estimate foraging raid
      rates and species composition of army ant communities in four Neotropical
      forests. The study sites spanned approximately 10 degrees latitude, with two
      sites each in Central and South America. 2. We recorded a total of 22 species of
      army ants. The four sites varied in observed and estimated species richness.
      Species overlap was highest between the Central American sites, and lowest
      between the South American sites. 3. Raid activity varied significantly among
      sites. Raid activity per kilometre of trail walks was over four times higher at
      the most active site (Sta. Maria, Venezuela) than at the least active site (Barro
      Colorado Island, Panama). Furthermore, each site showed a different diel pattern
      of activity. For example, raid activity was higher during daylight hours in Costa
      Rica, and higher at night in Venezuela. Raid activity relationships with ambient
      temperature also varied significantly among sites. 4. The overall rate of army
      ant raids passing through 1 m(2) plots was 0.73 raids per day, but varied among
      sites, from 0 raids per day (Panama) to 1.2 raids per day (Venezuela). 5.
      Primarily subterranean species were significantly more abundant in Venezuela, and
      above-ground foragers that form large swarm fronts were least abundant in Panama.
      The site heterogeneity in species abundance and diel activity patterns has
      implications for army ant symbionts, including ant-following birds, and for the
      animals hunted by these top predators.

PMID- 17439475
TI  - Smaller colonies and more solitary living mark higher elevation populations of a
      social spider.
AB  - 1. There appears to be a pattern of decreasing sociality with increasing
      elevation across social spider species in the genus Anelosimus at tropical
      latitudes. Our data suggest that this pattern holds within a single species,
      Anelosimus eximius, on a smaller altitudinal gradient. 2. In comparing colony
      size at six different altitudes in north-eastern Ecuador, we find that the
      lowland A. eximius populations tend to have larger colonies and few solitary
      females. At higher elevations, many of the colonies are small and the proportion
      of solitary females is greater. 3. Contrary to expectation, we also found no
      difference in spider density between the upper elevation and lowland populations.
      This result may be partly due to the fact that upper elevation populations occur
      only at the forest edge (as opposed to both edge and interior) where populations
      at all elevations appear more robust.

PMID- 17439476
TI  - Species interactions and population density mediate the use of social cues for
      habitat selection.
AB  - 1. The perspective that populations and communities are structured by
      antagonistic interactions among individuals has dominated much of ecology. Yet
      how animals use social information to guide decisions, such as habitat selection,
      may be influenced by both positive and negative interactions among individuals.
      Recent theory also suggests that the way animals use social information may be
      substantially influenced by population density, which alters the potential costs
      and benefits of such behaviours. 2. I manipulated cues of two competitors, the
      dominant least flycatcher Empidonax minimus (Baird & Baird) and the subordinate
      American redstart Setophaga ruticilla (Linnaeus), to assess the use of
      conspecific and heterospecific cues during habitat selection, and if population
      density influences these strategies. The experiment consisted of surveying birds
      during a pre-treatment year, which allows for the control and testing the effect
      of baseline densities, and a treatment year, in which treatments were applied
      just prior to settlement. Treatments included broadcasting songs of flycatchers
      and redstarts, and were compared with controls. 3. When controlling for pre
      treatment densities, bird densities, and to a lesser extent arrival dates, during
      the treatment year suggested that flycatchers were attracted to both conspecific
      and heterospecific cues during settlement. Furthermore, attraction was strongest
      for flycatchers in plots with moderate pre-treatment densities. American
      redstarts were rare in the study area but showed apparent attraction to
      conspecifics and avoidance of heterospecifics. 4. These results provide
      experimental evidence for the use of multiple social cues in habitat selection
      and suggest that heterospecific attraction may operate under broader contexts
      than originally envisioned. In such instances, nontarget effects can potentially
      occur when manipulating social cues to elicit settlement in conservation
      strategies. The impact of population density on the use of social cues shown here
      can also influence our understanding of metapopulation dynamics by causing
      complex threshold effects on the likelihood of rescue, which may influence
      metapopulation stability and the likelihood of local extinction.

PMID- 17439477
TI  - Structure and dynamics of an amphibian metacommunity in two regions.
AB  - 1. The concept of metacommunity is based on the hypothesis that species
      occurrence depends on species dynamics and interactions on local and regional
      scales via the movements of individuals between localities. Metacommunity
      approaches are currently being applied to pond breeding taxa such as amphibians.
      2. Given that animal movement is also influenced by the physical quality of the
      matrix to be crossed to reach a breeding habitat and by the affinity of the
      species for specific terrestrial habitats, matrix characteristics may enhance or
      hinder dispersal success. These characteristics would, in turn, affect the
      composition of larval assemblages at local level and, consequently, determine
      metacommunity structure and dynamics. 3. Here we compared the structures and
      dynamics of two metacommunities with the same pool of anurans along similar
      freshwater gradients in two regions that are well differentiated in terms of
      their respective terrestrial matrix. 4. Abundance of tadpole species and species
      assemblage in the two regions were determined principally by local processes (at
      pond level); however, the structure and dynamics of the communities differed. In
      one region species abundance was explained in part by landscape factors and
      consequently showed lower co-occurrence and lower colonization rates (species
      sorting models) indicating that terrestrial habitat could restrict animal
      movements, whereas in the other region higher co-occurrence and higher
      colonization rates (mass effect models) indicated low dispersal limitations.

PMID- 17439478
TI  - Predation as a landscape effect: the trading off by prey species between
      predation risks and protection benefits.
AB  - 1. Predators impose costs on their prey but may also provide benefits such as
      protection against other (e.g. nest) predators. The optimal breeding location in
      relation to the distance from a nesting raptor varies so as to minimize the sum
      of costs of adult and nest predation. We provide a conceptual model to account
      for variation in the relative predation risks and derive qualitative predictions
      for how different prey species should respond to the distance from goshawk
      Accipiter gentilis nests. 2. We test the model predictions using a comprehensive
      collection of data from northern Finland and central Norway. First, we carried
      out a series of experiments with artificial bird nests to test if goshawks may
      provide protection against nest predation. Second, we conducted standard bird
      censuses and nest-box experiments to detect how the density or territory
      occupancy of several prey species varies with distance from the nearest goshawk
      nest. 3. Nest predation rate increased with distance from goshawk nest indicating
      that goshawks may provide protection for birds' nests against nest predation.
      Abundance (or probability of presence) of the main prey species of goshawks
      peaked at intermediate distances from goshawk nests, reflecting the trade-off.
      The abundance of small songbird species decreased with distance from goshawk
      nests. The goshawk poses little risk to small songbirds and they may benefit from
      goshawk proximity in protection against nest predation. Finally, no pattern with
      distance in pied flycatcher territory (nest box) occupation rate or the onset of
      egg-laying was detected. This is expected, as flycatchers neither suffer from
      marked nest predation risk nor are favoured goshawk prey. 4. Our results suggest
      that territory location in relation to the nest of a predator is a trade-off
      situation where adult birds weigh the risk of themselves being predated against
      the benefits accrued from increased nest survival. Prey species appear able to
      detect and measure alternative predation risks, and respond adaptively. From the
      prey perspective, the landscape is a mosaic of habitat patches the quality of
      which varies according to structural and floristic features, but also to the
      spatial distribution of predators.

PMID- 17439479
TI  - Editors' note: Young Author of the Year Award - Elton Prize Nomination.

PMID- 17439480
TI  - Treatment with desipramine improves breathing and survival in a mouse model for
      Rett syndrome.
AB  - Rett syndrome (RS) is a severe X-linked neurological disorder in which most
      patients have mutations in the methyl-CpG binding protein2 (MECP2) gene. No
      effective treatment exists. We previously showed that the Mecp2-deficient mice, a
      mouse model of RS, have highly variable respiratory rhythm and frequent apneas
      due to reduced norepinephrine (NE) content, and a drastic decrease of tyrosine
      hydroxylase (TH)-expressing neurons in the medulla. We showed here that treating
      these mice with desipramine (DMI), which specifically inhibits NE reuptake,
      significantly improved their respiratory rhythm during several weeks. In
      addition, the treatment significantly extended their lifespan. At the cellular
      level, we showed that the reduced number of TH-expressing neurons before
      treatment in the mutant animals was not due to apoptosis. Conversely, we found
      that DMI treatment increased the number of TH-expressing neurons in the mutant
      brainstem to reach wild-type levels. We showed that this increase was not due to
      cellular proliferation. We propose that the Mecp2-deficient TH-expressing neurons
      lose their ability to synthesize TH at some point during their postnatal
      development. Our results suggest that a pharmacological stimulation of the
      noradrenergic system could be a promising approach for the treatment of the
      respiratory dysfunction which causes a significant proportion of death in RS
      patients.

PMID- 17439481
TI  - Recombinant human erythropoietin suppresses symptom onset and progression of G93A
      SOD1 mouse model of ALS by preventing motor neuron death and inflammation.
AB  - Multifactorial pathogenic mechanisms, including inflammation, attenuated survival
      signals and enhanced death signals, are involved in amyotrophic lateral sclerosis
      (ALS). Erythropoietin (EPO) has recently been highlighted as a cytokine with
      various potent neuroprotective effects, including reduction of inflammation,
      enhancement of survival signals and prevention of neuronal cell death. This study
      was undertaken to evaluate the effect of recombinant human EPO (rhEPO) on ALS
      model mice. We treated 96 ALS model mice with vehicle only, or 1, 2.5 or 5 imu of
      rhEPO/g of mouse once every other week after they were 60 days old. The treatment
      significantly prolonged symptom onset and life span, preserved more motor
      neurons, enhanced survival signals, and attenuated inflammatory signals in a dose
      dependent manner. These data suggest that treatment with rhEPO represents a
      potential therapeutic strategy for ALS.

PMID- 17439482
TI  - Wheel running following spinal cord injury improves locomotor recovery and
      stimulates serotonergic fiber growth.
AB  - Exercise, through manual step training, robotic step training or voluntary wheel
      running, is emerging as a promising therapy after spinal cord injury (SCI).
      Animal models provide a tool to investigate the mechanisms by which physical
      activity influences recovery from SCI. In the present study, we extend previous
      experiments showing improved recovery after SCI with both pre- and post-injury
      running in a flat-surface running wheel and investigate mechanisms of recovery.
      We tested a clinically relevant model using post-injury wheel running, in which
      we provided mice with access to wheels either 3 days or 7 days/week. Open field
      behavior, observed for 15 weeks following moderate T9 contusion injury, showed a
      significant linear increase in locomotor improvements across groups, sedentary, 3
      day runners and 7-day runners. Kinematic analysis of treadmill walking revealed
      that both wheel-running groups, 3 and 7 days/week, improved stepping ability
      compared with sedentary controls. Stereological quantification of neuron number
      in the injured segment of the spinal cord revealed no differences between the
      groups. However, stereological quantification of serotonin immunostaining using
      isotropic virtual planes showed increases in serotonin fiber length caudal to the
      lesion in the running groups. These observations suggest that improvement in
      function may be related to changes in serotonin fibers immediately caudal to the
      injury epicenter.

PMID- 17439483
TI  - Preservation of visual cortical function following retinal pigment epithelium
      transplantation in the RCS rat using optical imaging techniques.
AB  - The aim of this study was to determine the extent of cortical functional
      preservation following retinal pigment epithelium (RPE) transplantation in the
      Royal College of Surgeons (RCS) rat using single-wavelength optical imaging and
      spectroscopy. The cortical responses to visual stimulation in transplanted rats
      at 6 months post-transplantation were compared with those from age-matched
      untreated dystrophic and non-dystrophic rats. Our results show that cortical
      responses were evoked in non-dystrophic rats to both luminance changes and
      pattern stimulation, whereas no response was found in untreated dystrophic
      animals to any of the visual stimuli tested. In contrast, a cortical response was
      elicited in most of the transplanted rats to luminance changes and in many of
      those a response was also evoked to pattern stimulation. Although the
      transplanted rats did not respond to high spatial frequency information we found
      evidence of preservation in the cortical processing of luminance changes and low
      spatial frequency stimulation. Anatomical sections of transplanted rat retinas
      confirmed the capacity of RPE transplantation to rescue photoreceptors. Good
      correlation was found between photoreceptor survival and the extent of cortical
      function preservation determined with optical imaging techniques. This study
      determined the efficacy of RPE transplantation to preserve visual cortical
      processing and established optical imaging as a powerful technique for its
      assessment.

PMID- 17439484
TI  - Structural and functional recovery elicited by combined putrescine and
      aminoguanidine treatment after aspirative lesion of the fimbria-fornix and
      overlying cortex in the adult rat.
AB  - Damage to the adult CNS often causes permanent deficits. Based on a lesion model
      of septohippocampal pathway aspiration in the rat, we attempted to promote
      neuronal cell survival and post-traumatic recovery by using a pharmacological
      treatment combining aminoguanidine and putrescine (AGP). The functional recovery
      was followed over 15 weeks before morphological analysis. AGP treatment produced
      a persistent attenuation (approximately 50%) of the lesion-induced hyperactivity,
      a reduction (approximately 60%) in the sensorimotor impairments and an improved
      performance in the water-maze task which did not, however, rely upon improved
      memory capabilities. AGP weakened the lesion-induced decrease in ChAT-positive
      neurons in the medial septum and the extent of thalamic retrograde necrosis (by
      approximately 30% in each case) and resulted in a partial cholinergic
      reinnervation of the dentate gyrus. These promising results support the idea that
      coadministration of putrescine and aminoguanidine might become a potent way to
      foster structural and functional recovery (or compensation) in the adult
      mammalian CNS after injury.

PMID- 17439485
TI  - Enhancement of dopaminergic properties and protection mediated by neuronal
      activation of Ras in mouse ventral mesencephalic neurones.
AB  - The poor differentiation and survival of dopaminergic neurones are practical
      constraints in their therapeutic applications. Here we explored the role of
      neuronally activated Ras in ventral mesencephalon-derived neurospheres generated
      from synRas mouse embryos. The expression of Val12 Ha-Ras transgene and enhanced
      Ras activity was evident after differentiation of the neurospheres with a
      corresponding activating phosphorylation of mitogen-activated protein kinase.
      Phosphorylation of Akt/PKB, the target kinase of phosphoinositide 3-kinase, along
      with phosphorylation of Bad and CREB were enhanced in synRas-derived
      differentiated neurosphere cultures. Furthermore, increased Nurr1 expression was
      associated with elevated numbers of dopaminergic neurones in synRas-derived
      cultures compared with the wild-type. Correspondingly, tyrosine hydroxylase
      promoter assays revealed enhanced transcriptional activation of the promoter in
      synRas-derived cultures. synRas-derived dopaminergic neurones were greatly
      resistant to degeneration induced by various noxious stimuli. Consistently, the
      transgenic expression of activated Ras attenuated the adverse 6-hydroxydopamine
      effects on dopaminergic neurones. Dopaminergic neurones derived from both wild
      type and synRas cultures expressed voltage-gated potassium and sodium currents,
      fired action potentials and exhibited electrical network activity. Thus,
      expression of the transgene promotes survival and enhances differentiation
      towards a dopaminergic cell fate without altering their basic electrical
      properties. Our results suggest that intracellular cell therapy mimicking trophic
      signalling may offer potential benefit in models of human disease associated with
      dopamine neurone dysfunction.

PMID- 17439486
TI  - Valproate robustly increases Sp transcription factor-mediated expression of the
      dopamine transporter gene within dopamine cells.
AB  - Several lines of evidence suggest that valproate, a drug used in the treatment of
      mania and bipolar disorders, epilepsies, and addictions, may modulate dopamine
      transporter (DAT) function, yet the effects of valproate on DAT gene expression
      have not been directly assessed. Utilizing a human dopaminergic cell line and rat
      midbrain dopamine (DA) neurons in organotypic culture, we found that valproate
      increased endogenous DAT gene expression in a concentration- and time-dependent
      manner. Given previous data demonstrating that members of the specificity protein
      (Sp) family of transcription factors are strong trans-activators of DAT gene
      transcription, we investigated the Sp-dependence of valproate effects. Valproate
      induced transcription of a DAT reporter construct was significantly attenuated by
      coexpression of a dominant negative form of Sp, mutation of a Sp-responsive cis
      element, or expression in a Sp-null cellular background (SL-2 cells). Valproate
      significantly altered Sp protein abundance in both dopaminergic model systems
      employed. In summary, valproate treatment significantly increased DAT gene
      expression in a Sp transcription factor-dependent manner. Some of valproate's
      therapeutic effects may involve activation of DAT gene expression.

PMID- 17439487
TI  - Embryonic motor neuron dendrite growth is stunted by inhibition of nitric oxide
      dependent activation of soluble guanylyl cyclase and protein kinase G.
AB  - We have examined the participation of a neuronal nitric oxide synthase (nNOS)
      signaling pathway in the elaboration of motor neuron dendrites during embryonic
      life. During chick embryogenesis, nNOS is expressed by interneurons that surround
      the motor neuron pools in the ventral horn. Pseudorabies virus tracing suggests
      that these cells, while juxtaposed to motor neurons are not synaptically
      connected to them. The downstream effectors, soluble guanylyl cyclase (sGC) and
      protein kinase G (PKG), are found in motor neurons as well as several other
      populations of spinal cord cells. To determine the functional significance of the
      nNOS/sGC/PKG signaling pathway, pharmacological inhibitors were applied to chick
      embryos and the effects on motor neuron dendrites monitored. Inhibition of nNOS
      activity led to a lasting reduction in the overall size and degree of branching
      of the dendritic tree. These alterations in dendritic architecture were also seen
      when the activity of sGC or PKG was blocked. Our results suggest that normal
      motor neuron dendrite elaboration depends, in part, on the activity-dependent
      generation of NO by ventral horn interneurons, which then activates sGC and PKG
      in motor neurons.

PMID- 17439488
TI  - A quantitative trait locus on chromosome 18 is a critical determinant of
      excitotoxic cell death susceptibility.
AB  - C57BL/6J (B6) and FVB/NJ (FVB) mice are phenotypically distinct in their
      susceptibility to seizure-induced cell death after kainate administration.
      Previous studies using quantitative trait loci (QTLs) mapping established that
      the distal region of mouse chromosome 18 contains a gene(s) that is probably
      responsible for the difference in seizure-induced cell death susceptibility
      between two inbred strains, B6 and FVB, that are relatively resistant and
      susceptible, respectively, to seizure-induced cell death. The genetic locus has
      been mapped to a approximately 12-centimorgan region of chromosome 18, designated
      as seizure-induced cell death 1 (Sicd1). In order to confirm the Sicd1 QTL, we
      have developed congenic mouse strains containing the relevant donor segment from
      the resistant B6 strain on the susceptible FVB background, also referred to as
      the FVB.B6-Sicd1 congenic strain. Congenic and FVB littermate controls were
      tested in a seizure-induced cell death paradigm. The presence of B6 chromosome 18
      alleles on an FVB genetic background conferred protection against seizure-induced
      cell death, as compared with FVB littermate controls. To further localize the
      Sicd1 QTL, new congenic lines carrying overlapping intervals of the B6 segment
      were created [interval-specific congenic lines (ISCLs)-1-4] and assessed for
      seizure-induced cell death phenotype. All of the ISCLs exhibited reduced cell
      death associated with the B6 phenotype, as compared with the parental FVB strain.
      The most dramatic of these, ISCL-4, showed a nearly four-fold reduction in the
      extent of seizure-induced cell death. This suggests that ISCL-4 contains the
      putative gene(s) of the Sicd1 QTL.

PMID- 17439489
TI  - Severely impaired neuromuscular synaptic transmission causes muscle weakness in
      the Cacna1a-mutant mouse rolling Nagoya.
AB  - The ataxic mouse rolling Nagoya (RN) carries a missense mutation in the Cacna1a
      gene, encoding the pore-forming subunit of neuronal Ca(v)2.1 (P/Q-type) Ca2+
      channels. Besides being the predominant type of Ca(v) channel in the cerebellum,
      Ca(v)2.1 channels mediate acetylcholine (ACh) release at the peripheral
      neuromuscular junction (NMJ). Therefore, Ca(v)2.1 dysfunction induced by the RN
      mutation may disturb ACh release at the NMJ. The dysfunction may resemble the
      situation in Lambert-Eaton myasthenic syndrome (LEMS), in which autoantibodies
      target Ca(v)2.1 channels at NMJs, inducing severely reduced ACh release and
      resulting in muscle weakness. We tested neuromuscular function of RN mice and
      characterized transmitter release properties at their NMJs in diaphragm, soleus
      and flexor digitorum brevis muscles. Clinical muscle weakness and fatigue were
      demonstrated using repetitive nerve-stimulation electromyography, grip strength
      testing and an inverted grid hanging test. Muscle contraction experiments showed
      a compromised safety factor of neuromuscular transmission. In ex vivo
      electrophysiological experiments we found severely impaired ACh release. Compared
      to wild-type, RN NMJs had 50-75% lower nerve stimulation-evoked transmitter
      release, explaining the observed muscle weakness. Surprisingly, the reduction in
      evoked release was accompanied by an approximately 3-fold increase in spontaneous
      ACh release. This synaptic phenotype suggests a complex effect of the RN mutation
      on different functional Ca(v)2.1 channel parameters, presumably with a positive
      shift in activation potential as a prevailing feature. Taken together, our
      studies indicate that the gait abnormality of RN mice is due to a combination of
      ataxia and muscle weakness and that RN models aspects of the NMJ dysfunction in
      LEMS.

PMID- 17439490
TI  - Subventricular zone-derived neuroblast migration to the olfactory bulb is
      modulated by matrix remodelling.
AB  - In the rodent brain neural progenitor cells are born in the subventricular zone
      and migrate along a pathway called the rostral migratory stream (RMS) into the
      olfactory bulb where they differentiate into several classes of interneurones. In
      the adult, tangential migration in the RMS takes place in 'chains' of cells
      contained within glial tubes. In contrast, neonatal neuroblasts along the RMS
      lack these defined glial tubes and chains, migrating instead as individual cells.
      Time-lapse confocal microscopy of neuroblasts at each of these ages shows that
      individual cells migrate in a saltatory manner with bursts of high speed followed
      by periods of slower speed. Tangential migration within a glial tube is 20%
      faster than migration as individual cells. Neuroblasts may also interact and
      modify the extracellular matrix during migration through expression of a family
      of proteins, the matrix metalloproteinases (MMPs). MMPs are present and active
      along the subventricular zone-olfactory bulb pathway. In the presence of
      inhibitors of MMPs, neuroblast migration rates were reduced only when cells
      migrate individually. Chain migration in the adult was unaffected by MMP
      inhibitors. Taken together, these data suggest that MMPs only influence migration
      as individual cells and not as chains.

PMID- 17439491
TI  - High pressure modulation of NMDA receptor dependent excitability.
AB  - Pressure above 1.1 MPa induces in mammals and humans the high pressure
      neurological syndrome (HPNS). HPNS is characterized by cognitive and motor
      decrements associated with sleep disorders, EEG changes, tremor, and convulsions
      that ultimately may lead to death. Previous theories proposed that augmented
      response of the glutamatergic N-methyl-D-aspartate receptor (NMDAR) or reduced
      GABAergic inhibition may be involved. Recently, we have reported that isolated
      NMDAR response was augmented at high pressure. We now test whether this
      augmentation induces neuronal hyperexcitability. We studied high pressure effects
      on pharmacologically isolated NMDAR field excitatory postsynaptic potentials
      (fEPSPs) and on their efficacy in generating population spikes (PSs). Sprague
      Dawley male rats were used. Hippocampal coronal brain slices were prepared,
      constantly superfused with physiological solutions, gas-saturated at normobaric
      pressure, and compressed up to 10.1 MPa with helium. fEPSPs and PSs were recorded
      from the dendritic and the somatic layers of CA1 pyramidal neurons in response to
      Schaefer collaterals stimulation with trains of five stimuli at 25 Hz. Pressure
      caused PSs to appear earlier in the train. However, PS delay, rise time and decay
      time were increased and PS amplitude, frequency, and number were decreased in the
      last responses in the train. The decrease in late fEPSPs was associated with a
      reduction of the total number of PSs in the train, apparently without a change in
      the synaptic efficacy. These results may partially explain the neuronal
      hyperexcitability observed at pressure. Therefore, it is postulated that
      significant hyperexcitability is attained at pressure only when the normal fast
      fEPSP is intact.

PMID- 17439492
TI  - Central nervous system and non-central nervous system antigen vaccines exacerbate
      neuropathology caused by nerve injury.
AB  - Previously, we showed that autoimmune (central nervous system myelin-reactive) T
      cells exacerbate tissue damage and impair neurological recovery after spinal cord
      injury. Conversely, independent studies have shown T cell-mediated
      neuroprotection after spinal cord injury or facial nerve axotomy (FNAx). The
      antigen specificity of the neuroprotective T cells has not been investigated
      after FNAx. Here, we compared the neuroprotective capacity of autoimmune and non
      autoimmune lymphocytes after FNAx. Prior to axotomy, C57BL/6 mice were immunized
      with myelin basic protein, myelin oligodendrocyte glycoprotein (MOG) or ovalbumin
      (a non-self antigen) emulsified in complete Freund's adjuvant (CFA). FNAx mice
      receiving injections of phosphate-buffered saline (PBS) only (unimmunized) or
      PBS/CFA emulsions served as controls. At 4 weeks after axotomy, bilateral facial
      motor neuron counts were obtained throughout the facial motor nucleus using
      unbiased stereology (optical fractionator). The data show that neuroantigen
      immunizations and 'generic' lymphocyte activation (e.g. PBS/CFA or ovalbumin/CFA
      immunizations) exacerbated neuron loss above that caused by FNAx alone. We also
      found that nerve injury potentiated the effector potential of autoimmune
      lymphocytes. Indeed, prominent forelimb and hindlimb motor deficits were
      accompanied by disseminated neuroinflammation and demyelination in FNAx mice
      receiving subencephalitogenic immunization with MOG. FNAx or neuroantigen (MOG or
      myelin basic protein) immunization alone did not cause these pathological
      changes. Thus, irrespective of the antigens used to trigger an immune response,
      neuropathology was enhanced when the immune system was primed in parallel with
      nerve injury. These data have important implications for therapeutic vaccination
      in clinical neurotrauma and neurodegeneration.

PMID- 17439493
TI  - Functional presynaptic HCN channels in the rat globus pallidus.
AB  - Hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels are
      expressed postsynaptically in the rodent globus pallidus (GP), where they play
      several important roles in controlling GP neuronal activity. To further elucidate
      the role of HCN channels in the GP, immunocytochemical and electrophysiological
      approaches were used to test the hypothesis that HCN channels are also expressed
      presynaptically on the local axon collaterals of GP neurons. At the electron
      microscopic level, immunoperoxidase labelling for HCN1 and HCN2 was localized in
      GP somata and dendritic processes, myelinated and unmyelinated axons, and axon
      terminals. One population of labelled terminals formed symmetric synapses with
      somata and proximal dendrites and were immunoreactive for parvalbumin, consistent
      with the axon collaterals of GABAergic GP projection neurons. In addition,
      labelling for HCN2 and, to a lesser degree, HCN1 was observed in axon terminals
      that formed asymmetric synapses and were immunoreactive for the vesicular
      glutamate transporter 2. Immunogold labelling demonstrated that HCN1 and HCN2
      were located predominantly at extrasynaptic sites along the plasma membrane of
      both types of terminal. To determine the function of presynaptic HCN channels in
      the GP, we performed whole-cell recordings from GP neurons in vitro. Bath
      application of the HCN channel blocker ZD7288 resulted in an increase in the
      frequency of mIPSCs but had no effect on their amplitude, implying that HCN
      channels tonically regulate the release of GABA. Their presence, and predicted
      role in modulating transmitter release, represents a hitherto unidentified
      mechanism whereby HCN channels influence the activity of GP neurons.

PMID- 17439494
TI  - Chronic liver failure in rats impairs glutamatergic synaptic transmission and
      long-term potentiation in hippocampus and learning ability.
AB  - Cognitive function is impaired in patients with liver disease by unknown
      mechanisms. Long-term potentiation (LTP) in the hippocampus is considered the
      basis of some forms of learning and memory. The aims of this work were to assess
      (i) whether chronic liver failure impairs hippocampal LTP; (ii) if this
      impairment may be due to alterations in glutamatergic neurotransmission, and
      (iii) if impairment of LTP is associated with reduced learning ability. It is
      shown that liver failure in Wistar rats induces the following alterations in the
      hippocampus; (i) alters the phosphorylation of NMDA and AMPA receptors; (ii)
      reduces the expression of NMDA and AMPA receptors in membranes, (iii) reduces the
      magnitude of excitatory postsynaptic potentials (EPSPs) induced by activation of
      NMDA or AMPA receptors, and (iv) impairs NMDA receptor-dependent LTP. Liver
      failure also impairs learning of the Morris water maze task. Impairment of
      glutamatergic synaptic transmission and NMDA receptor-mediated responses may be
      involved in the alterations of cognitive function in patients with liver disease.

PMID- 17439495
TI  - Motor activity is modulated via different neuronal circuits in rats with chronic
      liver failure than in normal rats.
AB  - The mechanisms by which liver failure alters motor function remain unclear. It
      has been suggested that liver disease alters the neuronal circuit between basal
      ganglia and cortex that modulates motor function. Activation of group I
      metabotropic glutamate receptors in the nucleus accumbens (NAcc) by injecting (S)
      3,5-dihydroxyphenylglycine (DHPG) activates this circuit and induces locomotion
      We analysed by in vivo brain microdialysis the function of the circuits that
      modulate motor function in rats with liver failure due to portacaval shunt (PCS).
      We inserted cannulae in the NAcc and microdialysis probes in the NAcc, ventral
      pallidum (VP), substantia nigra pars reticulata (SNr), medio-dorsal thalamus
      (MDT), ventro-medial thalamus (VMT) or prefrontal cortex (PFCx). We injected DHPG
      in the NAcc and analysed extracellular neurotransmitters concentration in these
      areas. The results indicate that in control rats DHPG induces locomotion by
      activating the 'normal' neuronal circuit: NAcc --> VP --> MDT --> PFCx. In PCS
      rats this circuit is not activated. In PCS rats, DHPG injection activates an
      'alternative' circuit: NAcc --> SNr --> VMT --> PFCx. This circuit is not
      activated in control rats. DHPG injection increases dopamine in the NAcc of
      control but not of PCS rats, and glutamate in PCS but not in control rats. DHPG
      induced increase in dopamine would activate the 'normal' neuronal circuit, while
      an increase in glutamate would activate the 'alternative' circuit. The
      identification of the mechanisms responsible for altered motor function and
      coordination in liver disease would allow designing treatments to improve motor
      function in patients with hepatic encephalopathy.

PMID- 17439496
TI  - Behavioural and neural deficits induced by rotenone in the pond snail Lymnaea
      stagnalis. A possible model for Parkinson's disease in an invertebrate.
AB  - Parkinson's disease is a neurodegenerative disorder, related to the loss of
      dopamine (DA)-containing neurons in the substantia nigra. In experimental
      animals, both vertebrates and invertebrates, rotenone, a commercially available
      organic pesticide, induces symptoms of Parkinson's disease. We found that that
      rotenone is toxic to the pond snail Lymnaea stagnalis (4-day LC50 0.8 microM).
      Rotenone, at concentrations from 0.1 to 5 microM, caused progressive and
      irreversible behavioural deficits in both acute and chronic exposure. Chronic
      exposure to 0.5 microM rotenone led to a progressive decrease in spontaneous
      locomotion and in feeding, reaching almost 100% inhibition of both behaviours by
      the 7th day of rotenone treatment. In the central nervous system preparation made
      on the 7th day of treatment the postsynaptic potentials evoked by the identified
      dopaminergic RPeD1 neuron disappeared whereas the synaptic inputs received by the
      RPeD1 from a peptidergic neuron (VD4) were still functional. Immunostaining
      revealed that the tyrosine hydroxylase immunoreactivity decreased below the
      detectable level in both the RPeD1 cell body and its axonal processes. Finally,
      HPLC assay showed a significant (25%) decrease in DA level in the CNS by the 7th
      day of rotenone treatment. We conclude that, as in vertebrates, rotenone disrupts
      feeding and locomotion of the model mollusc Lymnaea stagnalis. One possible
      target of rotenone is the dopaminergic neurons in the CNS. We therefore suggest
      that Lymnaea stagnalis is a suitable invertebrate model for the study of
      Parkinson's disease, allowing direct analysis of the response of dopaminergic
      systems to rotenone at behavioural, cellular and neuronal levels.

PMID- 17439497
TI  - Nigrostriatal lesion induces D2-modulated phase-locked activity in the basal
      ganglia of rats.
AB  - There is a debate as to what modifications of neuronal activity underlie the
      clinical manifestations of Parkinson's disease and the efficacy of
      antiparkinsonian pharmacotherapy. Previous studies suggest that release of
      GABAergic striatopallidal neurons from D2 receptor-mediated inhibition allows
      spreading of cortical rhythms to the globus pallidus (GP) in rats with 6
      hydroxydopamine-induced nigrostriatal lesions. Here this abnormal spreading was
      thoroughly investigated. In control urethane-anaesthetized rats most GP neurons
      were excited during the active part of cortical slow waves ('direct-phase'
      neurons). Two neuronal populations having opposite phase relationships with
      cortical and striatal activity coexisted in the GP of 6-hydroxydopamine-lesioned
      rats. 'Inverse-phase' GP units exhibited reduced firing coupled to striatal
      activation during slow waves, suggesting that this GP oscillation was driven by
      striatopallidal hyperactivity. Half of the pallidonigral neurons identified by
      antidromic stimulation exhibited inverse-phase activity. Therefore, spreading of
      inverse-phase oscillations through pallidonigral axons might contribute to the
      abnormal direct-phase cortical entrainment of basal ganglia output described
      previously. Systemic administration of the D2 agonist quinpirole to 6
      hydroxydopamine-lesioned rats reduced GP inverse-phase coupling with slow waves,
      and this effect was reversed by the D2 antagonist eticlopride. Because
      striatopallidal hyperactivity was only slightly reduced by quinpirole, other
      mechanisms might have contributed to the effect of quinpirole on GP oscillations.
      These results suggest that antiparkinsonian efficacy may rely on other actions of
      D2 agonists on basal ganglia activity. However, abnormal slow rhythms may promote
      enduring changes in functional connectivity along the striatopallidal axis,
      contributing to D2 agonist-resistant clinical signs of parkinsonism.

PMID- 17439498
TI  - Region-specific tolerance to cocaine-regulated cAMP-dependent protein
      phosphorylation following chronic self-administration.
AB  - Chronic cocaine self-administration can produce either tolerance or sensitization
      to certain cocaine-regulated behaviours, but whether differential alterations
      develop in the biochemical response to cocaine is less clear. We measured cocaine
      induced phosphorylation of multiple cAMP-dependent and -independent protein
      substrates in mesolimbic dopamine terminal regions following chronic self
      administration. Changes in self-administering rats were compared to changes
      produced by passive yoked injection to identify reinforcement-related regulation,
      whereas acute and chronic yoked groups were compared to identify the development
      tolerance or sensitization in the biochemical response to cocaine. Microwave
      fixed brain tissue was collected immediately following 4 h of intravenous cocaine
      administration, and subjected to Western blot analysis of phosphorylated and
      total protein substrates. Chronic cocaine produced region- and substrate-specific
      tolerance to cAMP-dependent protein phosphorylation, including GluR1(S845)
      phosphorylation in striatal and amygdala subregions and NR1(S897) phosphorylation
      in the CA1 subregion of the hippocampus. Tolerance also developed to cAMP
      independent GluR1(S831) phosphorylation in the prefrontal cortex. In contrast,
      sensitization to presynaptic regulation of synapsin(S9) phosphorylation developed
      in the hippocampal CA3 subregion while cAMP-dependent tyrosine hydroxylase(S40)
      phosphorylation decreased in striatal dopamine terminals. Cocaine-induced ERK and
      CREB(S133) phosphorylation were dissociated in many brain regions and failed to
      develop either tolerance or sensitization with chronic administration. Positive
      reinforcement-related correlations between cocaine intake and protein
      phosphorylation were found only in self-administering animals, while negative
      dose-related correlations were found primarily with yoked administration. These
      regional- and substrate-specific adaptations in cocaine-induced protein
      phosphorylation are discussed in view of their potential impact on the
      development of cocaine addiction.

PMID- 17439499
TI  - Exploring the physiological effects of double-cone coil TMS over the medial
      frontal cortex on the anterior cingulate cortex: an H2(15)O PET study.
AB  - Transcranial magnetic stimulation (TMS) using a double-cone coil over the medial
      frontal cortex has the potential to clarify the function of the anterior
      cingulate cortex (ACC) in cognition, emotion and mood disorders. Following
      demonstration of disruption of performance on psychological tasks closely linked
      to cingulate function using this TMS technique, the current study aimed to
      directly measure the regional distribution of physiological effects of
      stimulation in the brain with H2(15)O PET. Experiment 1 assessed the effect of
      increasing numbers of pulse trains of TMS on regional cerebral blood flow (rCBF).
      Experiment 2 assessed the capacity of medial frontal TMS to modulate brain
      activity associated with the Stroop task using medial parietal TMS as a control
      site of stimulation. SPM99 analyses, using the ACC as a region of interest,
      revealed clusters of increased rCBF during medial frontal TMS in Brodmann area 24
      and reduced rCBF in more ventral ACC, the latter occurring in both experiments.
      In a whole-brain analysis, striking changes in rCBF were observed distal to the
      ACC following medial frontal TMS. Although TMS reliably affected Stroop task
      performance in early trials, there was no interaction between TMS and Stroop
      condition in rCBF. Our results suggest that medial frontal TMS using the double
      cone coil can affect ACC activity. However, a number of more distal cortical
      areas were also affected in these experiments. These additional changes may
      reflect either 'downstream' effects of altered cingulate cortex activity or
      direct effects of the coil.

PMID- 17439500
TI  - Event-related potentials reflect heterogeneity of developmental prosopagnosia.
AB  - Event-related potential (ERP) studies of developmental prosopagnosia (DP) are
      rare. Previous ERP investigations have reported smaller N170 amplitude
      differences between faces and objects in at least three prosopagnosics. The
      present study is based on a combination of behavioural and electrophysiological
      assessment of face processing. The aim was to investigate the face-specificity of
      the N170 in both healthy subjects and a group of DP individuals (N = 4), using
      famous and nonfamous faces, caricatures and houses as stimuli. All prosopagnosic
      subjects showed impairments in recognition of famous faces, memory for faces and
      learning new faces in behavioural assessment. In healthy subjects the largest
      effects were found at parieto-occipital electrode positions (PO7 and PO8), along
      with a familiarity effect at these electrode positions. Thus, parieto-occipital
      areas appear to play an important role in face processing. Three prosopagnosics
      showed reliable N170 amplitude differences between faces and nonface stimuli,
      whereas one DP individual showed significantly reduced amplitude differences
      between faces and nonface objects. The behavioural and electrophysiological data
      support the idea that DP reflects a heterogeneous impairment and that face
      processing deficits are not necessarily correlated with a lack of face-specific
      N170.

PMID- 17439501
TI  - Review article: acidity and volume of the refluxate in the genesis of gastro
      oesophageal reflux disease symptoms.
AB  - BACKGROUND: A number of mechanisms, other than acid reflux, may be responsible
      for the symptoms of gastro-oesophageal reflux disease. AIM: To assess the
      importance of non-acid reflux mechanisms. METHODS: This review is based on
      presentations and discussion at a workshop, where specialists in the field
      analysed data relating to these mechanisms. RESULTS: Weakly acidic reflux, pH (4
      7), detected with impedance-pHmetry is associated with regurgitation and atypical
      gastro-oesophageal reflux disease symptoms. It is not clear whether pepsin and
      trypsin can elicit symptoms, but bile can elicit heartburn. The magnitude of
      reflux-induced oesophageal distension can be determined by high frequency
      ultrasonography and is not reduced by proton pump inhibition, suggesting that
      persisting symptoms 'on' a proton pump inhibitor may still be due to oesophageal
      distension by non-acidic reflux. Exaggerated longitudinal muscle contraction can
      induce non-acid-related heartburn. Preliminary studies showed a positive effect
      of baclofen, surgery or endoscopic procedures to reduce weakly acidic reflux.
      CONCLUSION: Mechanisms other than acid reflux are involved in some of the
      symptoms of gastro-oesophageal reflux disease. Controlled outcome studies are
      needed to clarify their roles and the indications for antireflux procedures in
      patients with persistent symptoms whilst 'on' a proton pump inhibitor.

PMID- 17439502
TI  - Systematic review: renal and other clinically relevant outcomes in hepatorenal
      syndrome trials.
AB  - BACKGROUND: Although reversal of pretransplant renal dysfunction in hepatorenal
      syndrome reduces post-transplant complications, the overall impact on morbidity
      and mortality requires clarification. AIM: To review trials of pharmacologic
      interventions in hepatorenal syndrome, with specific assessment of trial quality
      and study endpoints, including patient survival and renal outcome measures.
      METHODS: Literature search and selection was carried out by a single reviewer.
      Data extraction and quality analysis were carried out by two independent
      reviewers. RESULTS: Of 848 identified articles, 36 were eligible for inclusion.
      Twenty-one were full-text. Only 19% were randomized-controlled trials. About 50%
      of studies included only Type 1 hepatorenal syndrome patients. Serum creatinine,
      urine output and urine sodium were the most common renal outcome measures. Only
      42% defined a primary renal endpoint. About 88% of articles reported mortality
      rates. CONCLUSIONS: Existing literature of pharmacologic agents for use in
      hepatorenal syndrome is limited by poor study design, including non
      randomization, heterogeneous study populations, lack of power, and limited use of
      clinically relevant outcomes. There is insufficient information in most trials to
      judge the impact of pharmacologic therapy on mortality or rates of
      transplantation. The validity of renal outcome measures as surrogate markers of
      more clinically relevant endpoints has not been established.

PMID- 17439503
TI  - Sustained virological response to interferon reduces cirrhosis in chronic
      hepatitis C: a 1,386-patient study from Taiwan.
AB  - BACKGROUND: The long-term benefits of interferon-based therapy on preventing
      cirrhosis at non-cirrhotic stage in chronic hepatitis C patients are not fully
      clarified. AIM: To evaluate the effectiveness of interferon-based therapy
      regarding to cirrhosis prevention in non-cirrhotic chronic hepatitis C patients.
      METHODS: A total of 1386 biopsy-proven, non-cirrhotic chronic hepatitis C
      patients (892 received interferon-based therapy and 494 untreated) were enrolled.
      RESULTS: Fifty-six untreated and 51 treated (24 sustained virologic responders
      and 27 non-responders) patients developed cirrhosis during a mean follow-up
      period of 5.0 (1-16) and 5.1 (1-15.3) years, respectively. The annual incidences
      of cirrhosis in untreated and treated groups were 2.26 and 1.11% (non-responders:
      1.99%, sustained responders: 0.74%), respectively. The 15-year cumulative
      incidence of cirrhosis was significantly lower in treated (9.9%) than untreated
      patients (39.8%, P = 0.0008, log-rank test). The 14.5-year cumulative incidence
      of cirrhosis was significantly lower in sustained responders (4.8%) compared with
      non-responders (21.6%, P = 0.0007) and untreated patients (36.6%, P < 0.0001).
      The difference was not significant between non-responders and untreated controls.
      Cox proportional hazards regression showed sustained virologic responders and
      younger age were independent negative factors for cirrhosis development.
      CONCLUSION: A sustained virologic response secondary to IFN-based therapy could
      reduce cirrhosis development in chronic hepatitis C patients.

PMID- 17439504
TI  - A 5-year prospective study of the late resolution of chronic hepatitis C after
      antiviral therapy.
AB  - BACKGROUND: Persistence of hepatitis C virus (HCV) in serum is assured after any
      course of antiviral therapy that failed to obtain a sustained virological
      response. AIM: To evaluate the long-term effect on serum HCV-RNA of a course of
      pegylated-interferon and ribavirin therapy that was unable to obtain sustained
      response. METHODS: Serum HCV-RNA was determined at monthly intervals in 68 non
      responders, breakthroughs or relapsers and in 52 naive controls enrolled in a
      five-year study. RESULTS: Five genotype 2 or 3 patients (one non-responder, three
      breakthroughs, one relapser) cleared HCV-RNA after the end of therapy or relapse,
      and remained negative until the end of follow-up. HCV-RNA clearance rate in
      genotype 2 and 3 non-responders, breakthroughs or relapsers was higher than in
      controls with the same genotypes (22.7% vs. 0%; log-rank 9.62; P < 0.002). HCV
      RNA at the end of treatment or at relapse was <10(5) IU/mL in the five subjects
      who cleared the virus and <10(4) IU/mL in four of them. None of genotype 1 or 4
      subjects cleared HCV-RNA during follow-up. CONCLUSIONS: Late resolution of HCV
      infection is possible in genotype 2 or 3 patients with low viral load at the end
      of therapy or at relapse. In these subjects, HCV-RNA monitoring is advisable
      during the first year after therapy.

PMID- 17439505
TI  - Fibrosis progression occurs in a subgroup of heavy drinkers with typical
      histological features.
AB  - BACKGROUND: Studies using consecutive liver biopsies constitute an attractive
      approach to gaining insight into the pathogenesis of alcoholic liver disease.
      AIM: To analyse histological factors at baseline, which are predictive of
      fibrosis progression and recurrence of alcoholic hepatitis. RESULTS: A total of
      193 drinkers underwent consecutive biopsies at an interval of 4 years. At
      baseline, 20 had normal livers, 135 steatosis, five fibrosis and 33 alcoholic
      hepatitis. The fibrosis score increased from 1.07 +/- 0.07 to 1.7 +/- 0.94 (P <
      0.001). In multivariate analysis, only steatosis (P = 0.04), alcoholic hepatitis
      (P = 0.0004) and stage of fibrosis (P < 0.0001) were independent predictive
      factors of the fibrosis score at the second biopsy. Cirrhosis developed more
      frequently in patients with steatosis (11%) and alcoholic hepatitis (39%) than in
      others (0%, P < 0.0001). Alcoholic hepatitis recurred more frequently in patients
      with alcoholic hepatitis at baseline: 58% vs. 15%, P < 0.0001. In multivariate
      analysis, alcoholic hepatitis at the first biopsy was the only predictive factor
      of its recurrence (P < 0.0001). CONCLUSIONS: In a large cohort of drinkers with
      consecutive biopsies, steatosis, fibrosis stage and alcoholic hepatitis at
      baseline were independent predictive factors of fibrosis progression. In terms of
      mechanisms, we propose a novel concept of multiple hits of alcoholic hepatitis
      occurring in the same patient.

PMID- 17439506
TI  - Infliximab for the treatment of ulcerative colitis: outcomes in Oxford from 2000
      to 2006.
AB  - BACKGROUND: Infliximab has been shown to be of benefit in the treatment of
      ulcerative colitis but long-term colectomy rates remain unknown. AIMS: To review
      the rate of colectomy after infliximab for ulcerative colitis and to identify
      factors that might predict the need for colectomy. METHODS: We conducted a
      retrospective cohort study of patients with active ulcerative colitis treated
      with infliximab between 2000 and 2006. The primary outcome was colectomy-free
      survival. Disease and treatment characteristics and complications were
      documented. RESULTS: Thirty patients were treated with infliximab for refractory
      ulcerative colitis. Sixteen (53%) came to colectomy a median of 140 days after
      their first infusion (range 4-607). There was no difference in colectomy between
      those receiving infliximab for acute severe ulcerative colitis failing
      intravenous steroids (8/14) and out-patients with steroid-refractory ulcerative
      colitis (8/16). Only 17% (5/30) achieved a steroid-free remission after a median
      follow-up of 13 months (range 2-72). Univariate analysis showed that a younger
      age at diagnosis of colitis was significantly associated with an increased rate
      of colectomy (27.5 years vs. 38.7 years, P = 0.016). CONCLUSION: Over half the
      patients studied came to colectomy. Of those avoiding colectomy, only five (17%)
      sustained a steroid-free remission.

PMID- 17439507
TI  - Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is
      well tolerated and associated with lowered faecal calprotectin.
AB  - BACKGROUND: Inulin and oligofructose promote selective growth of saccharolytic
      bacteria with low inflammatory potential. OBJECTIVE: To test the effect of
      oligofructose-enriched inulin in patients with active ulcerative colitis. DESIGN:
      Prospective, randomized, placebo controlled pilot trial. Eligible patients had
      been previously in remission with mesalazine as maintenance therapy or no drug,
      and presented with a relapse of mild to moderate activity. They were treated with
      mesalazine (3 g/day) and randomly allocated to receive either oligofructose
      enriched inulin (12 g/day, p.o., n = 10) or placebo (12 g/day of maltodextrin,
      p.o., n = 9) for 2 week. Primary endpoint was the anti-inflammatory effect as
      determined by reduction of calprotectin and human DNA in faeces. RESULTS:
      Rachmilewitz score decreased in both groups, reaching statistical significance at
      day 14 (P < 0.05). Oligofructose-enriched inulin was well-tolerated and dyspeptic
      symptoms scale decreased significantly with active treatment but not with
      placebo. At day 7, an early significant reduction of calprotectin was observed in
      the group receiving oligofructose-enriched inulin (day 0: 4377 +/- 659 microg/g;
      day 7: 1033 +/- 393 microg/g, P < 0.05) but not in the placebo group (day 0: 5834
      +/- 1563 microg/g; day 7: 4084 +/- 1395 microg/g, n.s.). Changes in faecal
      concentration of human DNA were not significant. CONCLUSION: In active ulcerative
      colitis, dietary supplementation with oligofructose-enriched inulin is well
      tolerated and is associated with early reduction in faecal calprotectin.

PMID- 17439508
TI  - Assessment of thiopurine methyltransferase enzyme activity is superior to
      genotype in predicting myelosuppression following azathioprine therapy in
      patients with inflammatory bowel disease.
AB  - BACKGROUND: Myelosuppression occurs in 2-7% of inflammatory bowel disease (IBD)
      patients treated with azathioprine, and can be associated with reduced activity
      of thiopurine methyltransferase (TPMT) in some patients. It has been proposed
      that pretreatment assessment of TPMT status reduces the incidence of toxicity and
      is cost-effective. AIMS: To determine if screening for TPMT status predicts side
      effects to azathioprine in patients with IBD and to ascertain whether screening
      by TPMT enzyme activity or genotype is superior. METHODS: Sequential IBD patients
      were identified and azathioprine tolerance recorded. Blood was collected for
      measurement of TPMT activity and TPMT*3C, TPMT*3A and TPMT*2 genotypes. RESULTS:
      Of 130 patients, 25% stopped azathioprine because of toxicity. Four patients
      experienced severe myelosuppression (WCC < 2). Eleven of 17 patients with reduced
      TPMT activity were heterozygotes, including one patient with marked TPMT
      deficiency who experienced severe myelosuppression. There was no association
      between intermediate TPMT deficiency and any side-effect. CONCLUSIONS: Moderate
      reduction of TPMT activity in heterozygotes was not associated with toxicity, but
      very low TPMT activity caused severe myelosuppression in one patient. This would
      have been predicted by measuring TPMT activity but not by genotyping. Measurement
      of TPMT activity may therefore be superior to genotype in predicting severe
      myelosuppression.

PMID- 17439509
TI  - Does body mass index differ between patients with Barrett's oesophagus and
      patients with chronic gastro-oesophageal reflux disease?
AB  - BACKGROUND: Obesity has been demonstrated to be a risk factor for the development
      of gastro-oesophageal reflux disease (GERD). AIM: To perform a prospective cohort
      study to determine whether there was a difference in body mass index (BMI)
      between patients with GERD and patients with Barrett's oesophagus (BE). METHODS:
      We prospectively enrolled patients undergoing endoscopic evaluation for GERD and
      collected information regarding BMI, tobacco and/or alcohol use, and family
      history of GERD. Patients with non-erosive reflux disease underwent confirmatory
      24-h pH testing. RESULTS: Seven hundred and fifty one patients with GERD (mean +/
      s.d. age of 55.4 +/- 14.2 years, 74% male) entered the study, and BE was present
      in 165 (22%, 90% male, 79% Caucasian) patients. The mean GERD symptom duration
      was 10.3 +/- 0.4 years (range 1-62 years) with a mean body mass index of 27.8 +/-
      0.2 kg/m(2) (range 15-55) Compared with patients having GERD alone, patients with
      BE were more likely to be older (P = 0.001), male (P < 0.001), current or prior
      tobacco users (P = 0.002), and with greater duration of GERD symptoms (P <
      0.001). There was no significant difference in the BMI for patients with and
      without BE. CONCLUSIONS: While obesity is a risk factor for both GERD and BMI,
      patients with BE did not demonstrate increased BMI compared with patients having
      chronic GERD.

PMID- 17439510
TI  - Symptom overlap in patients with upper gastrointestinal complaints in the
      Canadian confirmatory acid suppression test (CAST) study: further psychometric
      validation of the reflux disease questionnaire.
AB  - BACKGROUND: The reflux disease questionnaire (RDQ) is a short, patient-completed
      instrument. AIMS: To investigate the psychometric characteristics of the RDQ in
      patients with heartburn-predominant (HB) and non-heartburn predominant (NHB)
      dyspepsia. METHODS: HB (n = 388) and NHB (n = 733) patients were randomized to
      esomeprazole 40 mg daily or twice daily for 1 week, followed by 3 weeks of
      esomeprazole 40 mg daily. RESULTS: High factor loadings (0.78-0.86) supported the
      'regurgitation' dimension of the RDQ. Overlapping factor loadings in the
      'heartburn' and 'dyspepsia' dimensions suggested symptom overlap. All dimensions
      demonstrated high internal consistency (Cronbach's alpha: 0.79-0.90). Intra-class
      correlation coefficients over 4 weeks were good (0.66-0.85). The RDQ showed good
      responsiveness over 4 weeks of treatment, with high effect sizes (> or =0.80).
      Moderate or large symptom improvements were reported by 90% and 77% of HB and NHB
      patients, respectively, following treatment. Patients who responded to acid
      suppression also experienced symptom benefits in all RDQ dimensions. CONCLUSIONS:
      The RDQ is reliable, valid and responsive to change in HB and NHB patients. The
      symptom overlap is important but need not play a major role in determining
      treatment strategy as both patient groups benefited from proton pump inhibitor
      treatment.

PMID- 17439511
TI  - Positive association between gastro-oesophageal reflux disease and irritable
      bowel syndrome in a Chinese population.
AB  - BACKGROUND: Gastro-oesophageal reflux disease and irritable bowel syndrome are
      common diseases which may be related. AIM: To examine the association between
      gastro-oesophageal reflux disease and irritable bowel syndrome in Chinese
      population in Hong Kong. METHODS: Randomly selected ethnic Chinese were invited
      to participate in a telephone survey in 1996. Gastro-oesophageal reflux disease
      was defined as subjects having heartburn and/or acid regurgitation once weekly or
      more. Irritable bowel syndrome was diagnosed according to the Rome I criteria.
      The association between gastro-oesophageal reflux disease and irritable bowel
      syndrome was calculated using a statistical model which allows the odds ratio to
      be measured. RESULTS: One thousand six hundred and forty-nine subjects completed
      the interview (response rate 62%). The population prevalence of gastro
      oesophageal reflux disease and irritable bowel syndrome were 5% and 4%,
      respectively. Thirteen per cent of subjects with gastro-oesophageal reflux
      disease and 11% with irritable bowel syndrome suffered from both gastro
      oesophageal reflux disease and irritable bowel syndrome. The OR of having gastro
      oesophageal reflux disease and irritable bowel syndrome together was estimated to
      be 3 (95% CI: 1.05, 6.27) indicating a positive association between the two
      diseases. This association occurred predominantly in male subjects [OR = 9.3,
      (95% CI: 2.3, 26.2)] but not as strong in females [OR = 1.5, (95% CI: 0.3, 4.3)].
      Younger subjects were statistically more prone to the two diseases. CONCLUSIONS:
      There is a positive association between gastro-oesophageal reflux disease and
      irritable bowel syndrome, and their association occurs predominantly in male
      subjects.

PMID- 17439512
TI  - Rabeprazole-based eradication therapy for Helicobacter pylori: a large-scale
      study in Japan.
AB  - BACKGROUND: Large-scale studies of rabeprazole-based Helicobacter pylori
      eradication therapy have not been reported in Japan. AIMS: To evaluate H. pylori
      eradication by rabeprazole-based therapy with reference to antibiotic
      susceptibility, CYP2C19 genotype, and rabeprazole and clarithromycin dosages.
      METHODS: From 35 centres 479 H. pylori-positive patients with gastric or duodenal
      ulcer were randomized to four treatment groups: Group 1 (10 mg rabeprazole + 750
      mg amoxicillin + 200 mg clarithromycin twice daily for 7 days); Group 2 (10 mg,
      750 mg, 400 mg); Group 3 (20 mg, 750 mg, 200 mg) and Group 4 (20 mg, 750 mg, 400
      mg). RESULTS: Eradication rates were 86% (102 of 119), 89% (97 of 109), 91% (106
      of 116) and 90% (104 of 115) for Groups 1-4, respectively. The eradication rate
      was 95% (360 of 379) for clarithromycin-susceptible strains, and 50% (30 of 60)
      for clarithromycin-resistant strains. The eradication rates were 88% (332 of 379)
      and 96% (77 of 80) in extensive metabolizers and poor metabolizers, respectively.
      CONCLUSIONS: Rabeprazole-based therapies achieved 50% eradication of
      clarithromycin-resistant H. pylori, and even achieved good rates in extensive
      metabolizers. Accordingly, rabeprazole can be recommended as part of a first-line
      proton pump inhibitor-based triple therapy for H. pylori.

PMID- 17439513
TI  - Acute exacerbation of pain in irritable bowel syndrome: efficacy of
      phloroglucinol/trimethylphloroglucinol. A randomized, double-blind, placebo
      controlled study.
AB  - BACKGROUND: Abdominal pain is the predominant symptom in irritable bowel syndrome
      patients. Phloroglucinol and its methylated derivative are antispasmodic agents
      acting on smooth muscle. AIM: To evaluate the efficacy of
      phloroglucinol/trimethylphloroglucinol on pain intensity during an acute
      exacerbation of pain of irritable bowel syndrome over a 1-week period treatment.
      METHODS: Irritable bowel syndrome Rome II patients seeking medical advice for an
      acute exacerbation of abdominal pain were randomized to
      phloroglucinol/trimethylphloroglucinol (62.2 mg P + 80 mg TMP) two pills three
      times daily or placebo for 7 days. Patients were included if they had a pain with
      a minimal intensity of 40 on a 100-mm visual analogue scale, and if pain occurred
      at least 2 days during the week previous inclusion. RESULTS: Three hundred and
      seven patients were included by 78 general practitioners. The intent-to-treat
      population included 300 patients, aged of 46.9 +/- 14.8 years (73% female). The
      relative decrease of pain intensity at day 7 was 57.8 +/- 31.7% vs. 46.3 +/-
      34.7% (Delta = 11.5 +/- 3.8%, [CI(95%): 4.0 ; 19.1], P = 0.0029) and the
      percentage of patients with at least a 50% decrease of pain intensity was 62% vs.
      47% (Delta = 15.3 +/- 5.7%, [CI(95%): 4.1 ; 26.5], P = 0.0078) in
      phloroglucinol/trimethylphloroglucinol and placebo groups, respectively.
      CONCLUSIONS: A 1-week phloroglucinol/trimethylphloroglucinol treatment
      significantly reduces pain intensity in irritable bowel syndrome patients
      consulting their general practitioners for pain exacerbation.

PMID- 17439514
TI  - Elastomer implants in faecal incontinence: a blind, randomized placebo-controlled
      study.
AB  - AIM: To test efficacy and safety of polydimethylsiloxane elastomer implants, a
      silicone biomaterial, in patients with severe faecal incontinence related to an
      impaired internal anal sphincter. METHODS: Subjects were randomized to receive
      three injections of 2.5 mL of either physiological saline or polydimethylsiloxane
      elastomer. After local anaesthesia, an 18 gauge, 2.5-in needle was inserted
      through the perianal skin and laid down into the intersphincteric space.
      Treatment (saline or polydimethylsiloxane elastomer) was administered by means of
      a ratchet gun. Three injections of 2.5 mL each were performed in the area of the
      internal anal sphincter at 3, 7 and 11 o'clock positions. Main end point was the
      percentage of subjects in each treatment arm experiencing a successful treatment,
      defined as a Cleveland Clinic Florida-Faecal Incontinence score <8, 3 months
      after treatment. Secondary end points were quality of life scores, weekly number
      of faecal incontinence episodes, subject acceptance and adverse events rate. Both
      patients and end point assessments were blinded to treatment. RESULTS: 44 women
      (64.3 +/- 9 years) with a baseline Cleveland Clinic Florida-Faecal Incontinence
      score > or =8 were enrolled prospectively; 22 received polydimethylsiloxane
      elastomer and 22 saline treatment. Treatment was well tolerated. At 3 months, the
      percentage of subjects experiencing a successful treatment was not different
      between polydimethylsiloxane elastomer and saline groups (23% vs. 27%,
      respectively, P = 0.73). Moreover, Cleveland Clinic Florida-Faecal Incontinence
      score was not significantly different between polydimethylsiloxane elastomer and
      saline groups (11.7 +/- 4.7 vs. 11.4 +/- 4.5, respectively, P = 0.79).
      CONCLUSIONS: Polydimethylsiloxane elastomer implants cannot be recommended for
      treatment of severe faecal incontinence related to impaired internal anal
      sphincter.

PMID- 17439515
TI  - Bone disease in primary biliary cirrhosis and renal tubular acidosis.

PMID- 17439517
TI  - The two clinico-epidemiological forms of hepatitis E.

PMID- 17439518
TI  - Fulminant liver failure from acute autochthonous hepatitis E in France:
      description of seven patients with acute hepatitis E and encephalopathy.
AB  - Fulminant hepatitis E has not been well characterized in industrialized
      countries. The aim of this study was to prospectively describe patients with
      acute hepatitis E presenting as fulminant hepatic failure, i.e. with
      encephalopathy and prothrombin index <50%. Between February 1997 and April 2005,
      seven patients with encephalopathy were diagnosed with acute hepatitis E using
      viral RNA detection. These patients were compared with 33 patients diagnosed with
      a mild form (absence of encephalopathy) of acute hepatitis E during the same time
      period. Patients were 65 +/- 11 years old. Five were active drinkers and six had
      chronic liver disease. All hepatitis E virus sequences evaluated (5/7) were of
      genotype 3. All patients but two died (71%). Four patients had no travel history.
      When compared with patients with a mild form of acute hepatitis E, active alcohol
      abuse and chronic liver disease were more frequent in patients with the severe
      form. Duration of hospitalization was longer. Aspartate transferase and bilirubin
      levels were significantly higher. Prothrombin index and accelerin levels were
      lower and death was more frequent. Acute nontravel-associated hepatitis E can
      appear as fulminant hepatitis with encephalopathy and coagulation disorders.
      Prognosis is severe and this may be due to the age at which it occurs and
      frequent underlying chronic liver disease.

PMID- 17439519
TI  - Autochthonous hepatitis E in southwest England.
AB  - Although autochthonous hepatitis E has been reported in developed countries, its
      extent and nature in the United Kingdom are unclear. The aim of the present study
      was to report the natural history, lifestyle risk factors and molecular
      epidemiology of autochthonous hepatitis E infection in southwest England. Three
      hundred and thirty-three patients with unexplained hepatitis were tested for
      markers of hepatitis E virus (HEV) infection over a 7-year period. HEV RNA
      isolated from the cases was amplified and characterized. Of the 333 patients, 21
      had autochthonous hepatitis E. Patients were middle-aged or elderly and males
      were more commonly affected. Clinical manifestations ranged from asymptomatic
      infection to severe hepatitis. Of the 21 patients, 20 recovered within 6 weeks.
      None of the cases had travelled to an area endemic for HEV. None of the patients
      were vegetarian and all ate pork. Of the 21 cases, 20 occurred in the spring,
      summer and autumn months. All polymerase-chain-reaction-confirmed cases carried
      HEV genotype 3, which bore close sequence homology to HEV circulating in UK pigs.
      In the United Kingdom, autochthonous hepatitis E may be more common than
      previously recognized. Although the mode of transmission remains to be
      determined, it may be a zoonosis with pigs as a reservoir. Hepatitis E should be
      considered a public health issue in the United Kingdom.

PMID- 17439520
TI  - Hepatitis E virus infection among animals in northern India: an unlikely source
      of human disease.
AB  - Hepatitis E virus (HEV) is a major cause of acute hepatitis in many developing
      countries. Based on data from nonendemic regions, an animal reservoir of HEV has
      been proposed; however, data from HEV-endemic regions are limited. We tested sera
      from 200 pigs, 98 chickens, 86 goats, 58 sheep and 30 buffaloes for anti-HEV IgG
      using two different enzyme immunoassays. Specificity of the detected antibodies
      was confirmed using inhibition assays. Stool specimens from 210 pigs, 94 piglets
      and 37 sheep were tested for HEV-RNA using nested amplification methods; the
      polymerase chain reaction products were sequenced and compared with known human
      and swine HEV sequences. Of the 200 swine sera, 193 and 195, respectively, tested
      positive in the two assays. All goat sera showed anti-HEV reactivity in both the
      assays. Inhibition studies confirmed the HEV specificity of antibodies detected
      in swine and goat sera using both the assays. Sera from sheep, buffalo and
      chickens also showed high rates of apparent reactivity, but inhibition studies
      were unable to confirm the specificity of reactions in these species. One faecal
      specimen showed amplification using Indian swine HEV-specific primers. The
      genomic sequence of the amplicon from this isolate had only 76-79% nucleotide and
      93% amino acid homology with human HEV isolates reported from India and other
      parts of the world, and most closely resembled swine HEV isolates from other
      parts of India. Infection with HEV or a related agent is widespread among animals
      in northern India. However, the swine HEV in India differs genetically from human
      HEV isolates, indicating that pigs may not play an important role in the spread
      of human hepatitis E in endemic regions.

PMID- 17439521
TI  - Clinical responders to antiviral therapy of chronic HCV infection show elevated
      antiviral CD4+ and CD8+ T-cell responses.
AB  - Chronic hepatitis C virus (HCV) infection is characterized by attenuated
      antiviral T-cell responses, making their detection and characterization a
      technological challenge. The role and the dynamics of antiviral T-cell responses
      during antiviral therapy are incompletely understood. To assess HCV-specific T
      cell responses during antiviral therapy of genotype-1-infected patients, we
      adopted a flow cytometric approach to comprehensively evaluate virus-specific
      CD4+ and CD8+ T-cell proliferative responses against pools of genotype- and
      subtype-specific serial, overlapping peptides spanning the entire virus. Studies
      in cross-sectional cohorts of treatment-naive (TN) patients , early and sustained
      clinical virological responders (EVRs and SVRs) or clinical nonresponders (NRs)
      showed that this proliferative assay had significantly greater sensitivity in
      detecting HCV-specific responses, compared with ex vivo cytokine flow cytometry.
      At the same time, it could be used to detect and quantify both CD4+ and CD8+
      responses simultaneously. EVRs and SVRs showed significantly more HCV-specific
      CD4+ and CD8+ responses, compared with either TN patients or NRs. This
      corresponded to a higher magnitude of responses as well as a greater breadth of
      reactivity with higher responses against the core/E1, NS3, NS4 and NS5b regions
      of the virus. Interestingly, both clinical responders and NRs showed higher
      cytomegalovirus-specific CD4+ responses, compared with TN patients. These results
      demonstrate an association between clinically successful antiviral therapy and
      enhanced magnitude and breadth of antiviral responses. Moreover, the study
      demonstrates the clinical relevance of this flow cytometric proliferation assay
      system, in combination with an unbiased library of viral peptides, in evaluating
      the biology of antiviral T-cell responses during infection and therapy.

PMID- 17439522
TI  - Characterization of full-length hepatitis C virus genotype 4 sequences.
AB  - Over 85% of the world's nearly 170 million hepatitis C virus (HCV)-infected
      subjects exist in regions of Africa, Southeast Asia and Middle Eastern countries
      where genotypes 4-6 are very common. In particular, HCV genotype 4 is highly
      prevalent in Egypt with more than 19% of the population infected and chronic HCV
      representing one of the top five leading causes of death, due in part to
      ineffective interferon alpha treatment against this genotype. Despite this, very
      little work has been carried out to characterize the sequence diversity of
      genotype 4, which will be critical to the development of effective vaccines and
      antiviral therapies against this genotype. As a result of the paucity of sequence
      data available for HCV genotype 4, for which only one full genome sequence is
      currently available, we were interested in characterizing additional genotype 4
      sequences and to provide reagents for amplification of this genotype. Here we
      describe seven unique HCV genotype 4a full genomes, in addition to a single
      genotype 4d genome, and characterize their sequence diversity in relation to
      other more closely characterized HCV genotypes.

PMID- 17439523
TI  - Correlation of amino acid variations within nonstructural 4B protein with initial
      viral kinetics during interferon-alpha-based therapy in HCV-1b-infected patients.
AB  - Chronic hepatitis C is a major cause of liver cirrhosis leading to chronic liver
      failure and hepatocellular carcinoma. Different hepatitis C virus (HCV) proteins
      have been associated with resistance to interferon-alpha-based therapy. However,
      the exact mechanisms of virus-mediated interferon resistance are not completely
      understood. The importance of amino acid (aa) variations within the HCV
      nonstructural (NS)4B protein for replication efficiency and viral decline during
      the therapy is unknown. We investigated pretreatment sera from 42 patients with
      known outcome to interferon-based therapy. The complete NS4B gene was amplified
      and sequenced. Mutational analyses of predicted conformational, functional,
      structural and phylogenetic properties of the deduced aa sequences were
      performed. The complete NS4B protein was highly conserved with a median frequency
      of 0.015 +/- 0.009 aa exchanges (median +/- SD, 4.00 +/- 2.31). Especially within
      the predicted transmembranous domains of the NS4B protein, the mean number of aa
      variations was low (median frequency, 0.013 +/- 0.013). Neither the number of aa
      variations nor specific aa exchanges were correlated with HCV RNA serum
      concentration at baseline. A rapid initial HCV RNA decline of >/=1.5 log(10)
      IU/mL at week 2 of interferon-based therapy was associated with a higher
      frequency of nonconservative aa exchanges within the complete NS4B protein in
      comparison with patients with a nonrapid HCV RNA decline (median frequency, 0.011
      +/- 0.005 vs 0.004 +/- 0.003, P = 0.006). Overall, the aa sequence of the NS4B
      protein was highly conserved, indicating an important role for replication in
      vivo. Amino acid variations with relevant changes of physicochemical properties
      may influence replication efficiency, associated with a rapid early virological
      response.

PMID- 17439524
TI  - Prolonged antiviral therapy for hepatitis B virus-infected health care workers: a
      feasible option to prevent work restriction without jeopardizing patient safety.
AB  - To prevent transmission of hepatitis B virus (HBV) from health care workers
      (HCWs) to patients, highly viraemic HCWs are often advised to restrict performing
      exposure prone procedures (EPPs). To prevent loss of highly qualified medical
      personnel and simultaneously minimize transmission risk to patients, we offered
      highly viraemic HCWs antiviral therapy and evaluated the effects of this
      strategy. Eighteen chronic HBV-infected HCWs have been monitored every 3-6 months
      for a median period of 5.6 years (range 1.1-12.5 years). Antiviral therapy was
      offered if HBV DNA was above 10(5) copies/mL and EPPs were performed or active
      liver disease was present. Median HBV DNA levels, the percentage of days with HBV
      DNA above 10(3), 10(4) and 10(5) copies/mL, and reduction of HBV DNA during
      antiviral treatment have been analysed for hepatitis B e antigen (HBeAg)-positive
      and HBeAg-negative HCWs separately. Prolonged viral suppression was achieved in
      both HBeAg-positive, as well as HBeAg-negative HCWs. In HBeAg-negative HCWs
      treatment with interferon or lamivudine maintained HBV DNA levels below 10(5)
      copies/mL. For HBeAg-positive HCWs continuous treatment with tenofovir or
      entecavir was essential for reaching low viraemia persistently. In 2004, median
      HBV DNA levels in both HBeAg-negative and HBeAg-positive HCWs were below 10(3)
      copies/mL and all HCWs executed their professional work full-range. For both
      HBeAg-positive and HBeAg-negative HCWs, antiviral treatment is effective in
      persistent suppression of virus levels below 10(5) copies/mL. This observation
      supports antiviral therapy as a viable management option instead of work
      restriction, with the provision of regular expert monitoring including
      quantification of HBV DNA.

PMID- 17439525
TI  - SEN virus co-infection among HCV-RNA-positive mothers, risk of transmission to
      the offspring and outcome of child infection during a 1-year follow-up.
AB  - SEN is a newly discovered blood-transmissible virus. Among its variants, SENV-D
      and -H are most often associated with non-A, -E hepatitis. Very little is known
      about the risk of vertical transmission of the virus. By using polymerase chain
      reaction with specific primers for SENV-D and -H, we investigated the prevalence
      of SENV-H and -D infection, the transmission rate of SENV infection and clinical
      features of SENV-infected children in 89 hepatitis C virus (HCV)-positive human
      immunodeficiency virus type 1-negative mothers. SENV infection was found in 36
      (40%) mothers, and SENV-D was more frequent than SENV-H infection (34/36, 94%vs
      5/36, 14%, P < 0.01). No difference in SENV infection rates was found between
      injection drug user (IDU) mothers (17/51, 33%) and mothers with no risk for
      bloodborne infection (19/38, 50%, P = ns). SENV-H infection was found only in IDU
      mothers and mothers with HCV genotype1b. Both SENV-D and -H can be transmitted to
      the offspring with an overall rate of 47%. Vertical transmission of HCV does not
      facilitate SENV infection of the offspring. Among 17 SENV-infected children, none
      was co-infected with HCV. Maternal HCV genotype or viral load does not interfere
      with mother-to-infant transmission of SENV. Persistence of SENV infection was
      demonstrated in 100% of infected children after 1-year follow-up, but none had
      clinical evidence of liver disease.

PMID- 17439526
TI  - Transient elastography: a new surrogate marker of liver fibrosis influenced by
      major changes of transaminases.
AB  - Liver stiffness was measured by transient elastography (FibroScan) in 228
      consecutive patients with chronic viral hepatitis, with (115) or without
      cirrhosis (113), to study its correlations with serum transaminases [alanine
      aminotransferase (ALT)], fibrosis stage and surrogate noninvasive markers of
      fibrosis (APRI, FORNS, FibroTest and hyaluronic acid). The dynamic profiles of
      serum transaminases and liver stiffness were compared by multiple testing in 31
      patients during a 6-month follow-up. We identified 8.3 and 14 kPa as the fibrosis
      >/=F2 and cirrhosis cut-offs, respectively: their sensitivities were 85.2%/78.3%;
      specificities 90.7%/98.2%; positive predictive values 93.9%/97.8%; negative
      predictive values 78.8%/81.6%; diagnostic accuracies 87.3%/88.2%. FibroScan
      performed better than the other surrogate markers of fibrosis (P < 0.001). Other
      than fibrosis, other factors independently associated with liver stiffness were
      ALT for all patients and chronic hepatitis patients (P < 0.001), and 12-month
      persistently normal ALT (biochemical remission, P < 0.001) in cirrhotics. In
      patients with biochemical remission either spontaneous or after antiviral therapy
      (48 of 228, 21%), liver stiffness was lower than in patients with identical
      fibrosis stage, but elevated ALT (P < 0.001). The liver stiffness dynamic
      profiles paralleled those of ALT, increasing 1.3- to 3-fold during ALT flares in
      10 patients with hepatitis exacerbations. Liver stiffness remained unchanged in
      21 with stable biochemical activity (P = 0.001). In conclusion, transient
      elastography is a new liver parameter that behaves as a reliable surrogate marker
      of fibrosis in chronic viral hepatitis patients, provided that its relationship
      with major changes of biochemical activity is taken into account.

PMID- 17439527
TI  - Preterm delivery and exposure to active and passive smoking during pregnancy: a
      case-control study from Italy.
AB  - The aim of this study was to assess the relationship between preterm/early
      preterm delivery and active smoking as well as environmental tobacco smoke (ETS)
      exposure in a sample of pregnant Italian women. A case-control study was
      conducted in nine cities in Italy between October 1999 and September 2000. Cases
      of preterm birth were singleton babies born before the 37th gestational week;
      babies born before the 35th gestational week were considered early preterm
      births. Controls were babies with gestational ages >or= 37th week. A total of 299
      preterm cases (including 105 early preterm) and 855 controls were analysed. A
      self-administered questionnaire was used to assess active smoking and ETS
      exposure, as well as potential confounders. Multivariable logistic regression
      analysis showed a relationship between active smoking during pregnancy and
      preterm/early preterm delivery [adjusted ORs: 1.53; 95% CI 1.05, 2.21 and 2.00;
      95% CI 1.16, 3.45, respectively]. A dose-response relationship was found for the
      number of cigarettes smoked daily. The adjusted ORs were 1.54 and 1.69 for
      preterm babies and 1.90 and 2.46 for early preterm babies for 1-10 and >10
      cigarettes/day respectively. ETS exposure was associated with early preterm
      delivery [adjusted OR 1.56; 95% CI 0.99, 2.46] with a dose-response relationship
      with the number of smokers in the home. Smoking during pregnancy was strongly
      associated with preterm delivery with a dose-response effect. ETS exposure in non
      smoking women was associated only with early preterm delivery.

PMID- 17439528
TI  - Does gravidity influence smoking behaviour in pregnancy? A comparison of
      multigravid and primigravid women.
AB  - This study used the data from a retrospective cross-sectional survey to describe
      the prevalence of smoking in pregnancy in a large UK sample, over more than 20
      years of pregnancies. The main objective was to determine whether women in their
      second or subsequent pregnancy are more or less likely than primigravidae to
      change their smoking behaviour. The participants were 7506 ever-pregnant women,
      from 7702 who answered the second stage of a survey of reproductive history in
      2001-02, sent to 10 828 women, aged 18-55 years on the UK electoral register.
      These women gave detailed information on their last pregnancy. The main outcome
      measure was self-reported cigarette consumption in the first trimester of
      pregnancy. Nineteen per cent (1417/7506) of women in this sample smoked in the
      first trimester of the reported pregnancy. The data showed that there had been a
      decrease over the last 20 years in smoking prevalence, but this trend was not
      statistically significant after adjustment for confounding (P(trend) = 0.07).
      There was evidence that multigravidae were more likely to smoke in their
      pregnancies than were primigravidae (adjusted OR = 1.24, [95% CI 1.01, 1.53]),
      with a highly significant trend with increasing pregnancy order (P(trend) <
      0.0001). Over time, women who reported smoking before pregnancy (n = 1926),
      showed a decreasing trend in continuing to smoke the same amount after
      recognising their pregnancies (P(trend) < 0.0001). After adjustment, multigravid
      smokers were almost 75% more likely than primigravid smokers to continue to smoke
      with no change in consumption (adjusted OR = 1.74, [95% CI 1.32, 2.28]), with a
      clear trend found with increasing pregnancy order (P(trend) = 0.001). In this UK
      population-based study, multigravidae were more likely to smoke in pregnancy than
      women pregnant for the first time. If already a smoker, they were much less
      likely to cut down their smoking once they found out they were pregnant,
      regardless of age. This suggests that a great deal of the burden of morbidity
      associated with smoking in pregnancy is in the multigravid group.

PMID- 17439529
TI  - Maternal reproductive and demographic characteristics as risk factors for
      hypospadias.
AB  - This study examined the association of hypospadias risk with several maternal
      reproductive and demographic characteristics: age, parity, body mass index (BMI),
      nausea and vomiting of pregnancy (NVP), multiple pregnancy, fertility treatments
      and procedures, education and race-ethnicity. The study included data on
      deliveries with estimated due dates from October 1997 to December 2000 that were
      part of the National Birth Defects Prevention Study, a multi-state case-control
      study of many birth defects. The analysis included 502 cases with second or third
      degree hypospadias (i.e. the urethra opened at the penile shaft, scrotum or
      perineum) and 1286 male, liveborn, non-malformed controls. Risks were estimated
      from a multivariable logistic regression model that included all exposures of
      interest. Results indicated particularly elevated risks among births to women who
      were primiparae, aged >or=35 years and had a BMI of >26, compared with women who
      were multiparae, aged <30 years and had a BMI of <or=26 [adjusted OR 12.5, 95% CI
      5.1, 30.8]. NVP at least once per day during the second or third month of
      pregnancy vs. no NVP was associated with slightly reduced risk [OR 0.8, 95% CI
      0.6, 1.1]. Multiple birth, fertility treatments and college education were
      associated with increased risks, and Hispanic race-ethnicity was associated with
      reduced risk. Although the potential contribution of underlying maternal
      endocrine parameters to the current findings are unknown, the results do provide
      clues regarding hypospadias aetiology that merit further investigation.

PMID- 17439530
TI  - Reliability and determinants of anogenital distance and penis dimensions in male
      newborns from Chiapas, Mexico.
AB  - Development of the perineum as well as the external genitalia is determined by
      dihydrotestosterone, resulting in a greater anogenital distance (AGD) in males
      than females. In animal experiments with hormonally active agents, anogenital
      distance is used as a bioassay of fetal androgen action. Use of anogenital
      distance in human studies has been rare. Because anogenital distance has been an
      easy-to-measure, sensitive outcome in animal studies, we developed an
      anthropometric protocol for measurement of anogenital distance in human males. In
      this paper we describe the method for measurement of three anogenital distances,
      their reliability, and an assessment of predictors for each in the context of an
      epidemiological study. We compare the reliabilities and predictors to those for
      stretched penis length and penis width. A cross-sectional study of 781 newly
      delivered male infants was conducted in 2002-03 in Chiapas, Mexico. Replicate
      measures were obtained on nearly all subjects. The reliability of the measures of
      anogenital distance (0.82-0.91) were higher than for stretched penis length
      (0.78) and width (0.75). Birthweight and gestational length were more strongly
      related to anogenital distance than to penis length. Anogenital distance was not
      related to penis length (r = 0.03). Our large study clearly shows that AGD can be
      measured well in newborn males, and that the measurements were more reliable than
      those of penis length. Whether AGD measures in humans relate to clinically
      important outcomes, however, remains to be determined, as does its utility as a
      measure of androgen action in epidemiological studies.

PMID- 17439531
TI  - Male factor infertility: a twin study.
AB  - There is a considerable body of literature on the causes of female infertility,
      but far less is known about male factor infertility. We conducted a classical
      twin study to estimate the genetic influence on 12-month male factor infertility.
      The study used the Vietnam Era Twin (VET) Registry, which includes male twin
      pairs born between 1939 and 1957, and who served in the US military between 1965
      and 1975. In 1987, a health survey was mailed to all twins and obtained a 74%
      response rate. The current analyses comprised 1795 complete pairs in which both
      twins were married only once. Proband-wise concordance rates, tetrachoric
      correlations, and a bivariate probit model were used to calculate estimates of
      familial clustering and heritability for male factor infertility. The proband
      concordance rate for male factor infertility was 38% [95% CI 32.8, 42.4] in
      monozygotic (MZ) pairs and 33% [95% CI 28.0, 38.6] in dizygotic (DZ) pairs. The
      tetrachoric correlations for male infertility were 0.15 in MZ and 0.04 in DZ
      pairs. This pattern provides evidence of familial clustering, although genetic
      influence was not evident (P = 0.21). The current study identified that 12-month
      male factor infertility clustered within families. However, results suggest that
      factors unique to individual twins may play a more prominent role in male
      infertility than additive genetic effects or the common environment.

PMID- 17439532
TI  - High familial risks for cerebral palsy implicate partial heritable aetiology.
AB  - Cerebral palsy is the commonest cause of severe childhood disability, the
      aetiology of which is largely unknown. Data on familial aggregation of cerebral
      palsy are very limited. We defined familial risks for siblings who were
      hospitalised because of cerebral palsy in Sweden. A nationwide database for
      neurological diseases was constructed by linking the Multigeneration Register to
      the Hospital Discharge Register for the years 1987-2001. Standardised
      hospitalisation ratios (SHRs) were calculated for affected singletons and twins
      by comparing them with siblings who had no cerebral palsy. A total of 3997
      patients were recorded with cerebral palsy. Familial cerebral palsy was uncommon,
      and it accounted for 1.6% of all cerebral palsy cases. However, for parents who
      had had one affected child the risk of recurrence in another child was
      considerably increased. Parents of one affected child had a 4.8-fold risk of
      having a second affected child, and where the siblings were twins, the risk was
      29-fold. These familial risks were particularly high in some clinical subgroups:
      17-25 in singletons and 37-155 in twins, including hemiplegia, diplegia and
      quadriplegia. The remarkably high familial risks are difficult to explain without
      some contribution of heritable factors. The lack of discordant pairs may suggest
      that heritable factors are disorder type-specific. Affected concordant sibling
      pairs should be subjected to molecular studies aiming at identifying the
      susceptibility gene.

PMID- 17439534
TI  - Maternal employment and breast-feeding initiation: findings from the Millennium
      Cohort Study.
AB  - Maternal employment rates have increased rapidly in recent years and little is
      known about how this influences whether women start breast feeding. We examined
      data from the Millennium Cohort Study to determine whether a mother's employment
      status (full-time, part-time, self-employed, on leave, not employed/student) and
      employment characteristics are related to breast-feeding initiation. This
      analysis comprised 14 830 white mothers from Britain and Ireland (6917 employed)
      with singleton babies, born from 2000 to 2002. Information was obtained on infant
      feeding history and mother's employment when the cohort child was 9 months old.
      We found that women employed full-time were less likely to initiate breast
      feeding than mothers who were not employed/students, after adjustment for
      confounding factors [adjusted rate ratio (aRR) = 0.92; 95% confidence interval
      (CI) 0.89, 0.96]; however, there were no differences in breast-feeding initiation
      between mothers employed part-time, self-employed, or on leave and mothers who
      were not employed/students. Among employed mothers, those who returned to work
      within 4 months postpartum were less likely to start breast feeding than women
      who returned at 5 or 6 months [aRR = 0.95; 95% CI 0.92, 0.99], and women who
      returned within the first 6 weeks were much less likely to start breast feeding
      [aRR = 0.85; 95% CI 0.77, 0.94]. Mothers returning for financial reasons were
      also less likely to initiate breast feeding [aRR = 0.96; 95% CI 0.93, 0.99] than
      those who returned for other reasons. Policies to increase breast feeding should
      address how both the time and circumstances of a mother's return to employment
      postpartum influence whether she decides to start breast feeding.

PMID- 17439535
TI  - A multivitamin supplementation and education intervention as an effective means
      of increasing multivitamin use among postpartum women of Mexican origin.
AB  - Postpartum Hispanic women in the USA are at elevated risk for neural tube defects
      in subsequent pregnancies from the combined effects of ethnicity, folate
      depletion from the prior pregnancy and lactation, and high parity rates with
      short inter-birth intervals. This study evaluated an education programme and
      distribution of a 3-month starter package of multivitamins among Hispanic women
      attending nutrition clinics for low-income women in El Paso, Texas. At 1-6 weeks
      postpartum, 329 subjects were selected to receive education only, multivitamins
      only, education and multivitamins, or no intervention. Multivariable regression
      obtained odds ratios (OR) and 95% confidence intervals [CI] to measure the
      association between intervention status and self-reported multivitamin use at
      least four times per week at 6 and 12 months postpartum, while controlling for
      potential confounding variables. Multivitamin distribution was related to
      consumption at both 6 months (OR = 3.5 [95% CI 1.1, 11.2]) and 12 months (OR =
      6.5 [95% CI 1.5, 28.3]). Multivitamins plus education was most effective in
      increasing multivitamin use at both periods: 6 months (OR = 4.0 [95% CI 1.53,
      11.7]) and 12 months (OR = 6.4 [95% CI 1.7, 24.2]). At enrolment, 66% of women
      regularly took vitamins, and approximately 35% took them at both 6 and 12 months
      postpartum. The education intervention alone was not associated with multivitamin
      use at either 6 months (OR = 0.79 [95% CI 0.3, 2.4]) or 12 months (OR = 3.1 [95%
      CI 0.8, 12.1]). Multivitamin use declines precipitously during postpartum at the
      time Hispanic women may be susceptible to a subsequent pregnancy. This study
      provides evidence that multivitamin starter packs sustain multivitamin usage up
      to 1 year postpartum for a specific high-risk group, but the effect of
      educational intervention alone should be further studied.

PMID- 17439537
TI  - Low-income minority mothers' reports of infant health care utilisation compared
      with medical records.
AB  - This study aimed to investigate mothers' reporting of the nature, location,
      frequency and content of health care visits for their infants, as compared with
      data abstracted from the infants' medical records. It was part of a community
      based parenting intervention designed to improve preventive health care
      utilisation among minority mothers in Washington, DC. Mothers >or=18 years old
      with newborn infants and with poor or no prenatal care were enrolled in the
      study. A total of 160 mother-infant dyads completed the 12-month study. Mothers
      were interviewed when the infants were 4, 8 and 12 months old, and were asked to
      recall infant visits to all health care providers. Medical records from
      identified providers were used for verification. The number and type of
      immunisations given, types of providers visited, and reason for the visits were
      compared. Only about a quarter of mothers agreed with their infants' medical
      records on the number of specific immunisations received. The mothers reported
      fewer polio (1.8 vs. 2.1, P = 0.006), diphtheria and tetanus toxoids and
      pertussis (DTP) (1.8 vs. 2.2, P = 0.002), and Haemophilus influenzae type b (HiB)
      (1.3 vs. 2.1, P < 0.0001) immunisations than were recorded. Similarly, about a
      quarter of the mothers were unaware of any polio, DTP or hepatitis B
      immunisations given, as documented in the medical records, and 38% did not know
      that their infant was immunised for HiB. Nearly half of the mothers recalled more
      infant doctors' visits than were recorded in the medical records (4.1 vs. 3.6
      visits, P = 0.017). The mothers generally disagreed with the providers about the
      reason for a particular visit and reported fewer sick-baby visits (1.5 vs. 3.3, P
      < 0.0001) than the providers recorded. Mothers' reports and medical records
      matched in only 19% of the cases. In 47%, mothers under-reported and in 34% over
      reported the total number of visits. The strongest agreement between mothers'
      reports and medical records was in the case of emergency room visits (63%). In
      conclusion, in this population, mothers' reporting did not match that of
      providers with respect to specific information: the number of immunisations, the
      location where services were provided, and the classification of sick- vs. well
      baby visits. Future studies that evaluate health care utilisation data should
      take these discrepancies into consideration in their selection of information
      source, and in their interpretation of the data.

PMID- 17439536
TI  - The Jerusalem Perinatal Study cohort, 1964-2005: methods and a review of the main
      results.
AB  - The Jerusalem Perinatal Study recorded information on population-based cohorts of
      92 408 live- and stillbirths in 1964-76, and their parents, with active
      surveillance of infant deaths and birth defects. Data on maternal conditions,
      obstetric complications and interventions during labour and delivery were
      recorded for 92% of the births. Subsets were surveyed with antenatal interviews
      in 1965-68 (n = 11 467), paediatric admissions to hospital (n = 17 782) and
      postpartum interviews in 1975-76 (n = 16 912). Data from some offspring were
      linked to records of a health examination at age 17. The offspring, mothers and
      fathers have been traced recently, their vital status assessed, and the data
      linked to Israel's Cancer Registry and Psychiatric Registry. This paper describes
      the different types of data available, their sources, and some potential biases.
      Characteristics of this unique population are shown. Findings from the study are
      reviewed and a list of references is provided. The cohorts provide a unique
      source of data for a wide variety of studies.

PMID- 17439538
TI  - Anticonvulsant therapy for status epilepticus.
AB  - AIMS: To determine whether a particular anticonvulsant is more effective or safer
      than another or placebo in patients with status epilepticus, and to summarize the
      available evidence from randomized controlled trials, and to highlight areas for
      future research in status epilepticus. METHODS: Randomized controlled trials of
      participants with premonitory, early, established or refractory status
      epilepticus using a truly random or quasi-random allocation of treatments were
      included. RESULTS: Eleven studies with 2017 participants met the inclusion
      criteria. Lorazepam was better than diazepam for reducing risk of seizure
      continuation [relative risk (RR) 0.64, 95% confidence interval (CI) 0.45, 0.90]
      and of requirement of a different drug or general anaesthesia (RR 0.63, 95% CI
      0.45, 0.88) with no statistically significant difference in the risk of adverse
      effects. Lorazepam was better than phenytoin for risk of seizure continuation (RR
      0.62, 95% CI 0.45, 0.86). Diazepam 30 mg intrarectal gel was better than 20 mg in
      premonitory status epilepticus for the risk of seizure continuation (RR 0.39, 95%
      CI 0.18, 0.86). CONCLUSIONS: Lorazepam is better than diazepam or phenytoin alone
      for cessation of seizures and carries a lower risk of continuation of status
      epilepticus requiring a different drug or general anaesthesia. Both lorazepam and
      diazepam are better than placebo for the same outcomes. In the treatment of
      premonitory seizures, diazepam 30 mg intrarectal gel is better than 20 mg for
      cessation of seizures without a statistically significant increase in adverse
      effects. Universally accepted definitions of premonitory, early, established and
      refractory status epilepticus are required.

PMID- 17439539
TI  - Pharmacokinetics of inhaled monodisperse beclomethasone as a function of particle
      size.
AB  - AIMS: For optimal efficacy, antiasthma drugs should be delivered to the desired
      region in the airways. To date, the optimal particle size for steroids in adults
      is not known. The aim of the study was to evaluate the pulmonary bioavailability
      for inhaled beclomethasone dipropionate (BDP) aerosols of different particle
      sizes. METHODS: In a randomized single-blind crossover trial, 10 mild asthmatic
      patients inhaled monodisperse BDP aerosols with mass median aerodynamic diameters
      (MMADs) of 1.5, 2.5 and 4.5 microm. Gastrointestinal absorption was blocked by
      activated charcoal. Plasma concentrations of 17-beclomethasone monopropionate (17
      BMP) were measured by liquid chromatography plus mass spectrometry. RESULTS:
      Aerosols with MMADs of 1.5 microm, 2.5 microm, and 4.5 microm gave mean maximum
      concentrations (C(max)) of 17-BMP of 475 pg ml(-1), 1300 pg ml(-1), and 1161 pg
      ml(-1), respectively. The area under the curve (AUC) values of 17-BMP for MMADs
      of 1.5 microm, 2.5 microm, and 4.5 microm were 825 pg ml(-1) h, 2629 pg ml(-1) h,
      and 2276 pg ml(-1) h, respectively. The mean terminal half-time of 17-BMP for all
      three aerosol sizes was around 1.5 h. CONCLUSIONS: Monodisperse BDP aerosols with
      a MMAD of 1.5 microm gave two-three fold lower values for C(max) and AUC than
      those with MMADs of 2.5 and 4.5 microm.

PMID- 17439541
TI  - Evaluation of real-time PCR for the detection and quantification of bacteria in
      chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) embraces a number of pathological
      processes including chronic bronchitis, chronic bronchiolitis and emphysema. The
      chronic and progressive course of COPD is often aggravated by short periods of
      increasing symptoms. Respiratory tract infections (RTIs) are the most common
      causes of COPD exacerbations. Detection and enumeration of respiratory bacteria
      are important techniques in diagnosing RTIs and in the validation of new
      treatment methods. We describe here the development and evaluation of real-time
      PCR assays for the simultaneous direct detection and quantification of a range of
      respiratory bacteria in individuals with COPD during stable periods and during
      acute exacerbations of the disease. Sputum samples from 30 subjects in a COPD
      study were analysed, and results compared with the current gold standard of
      culture. Real-time PCR assays proved highly sensitive, with no cross-reactivity
      with other species. The prevalence of bacteria detected by real-time PCR compared
      with that by culture was substantially higher for Streptococcus pneumoniae,
      Staphylococcus aureus, Haemophilus spp. and Moraxella catarrhalis. Multiple
      pathogens were also found with real-time PCR but were not detected by culture.
      This study demonstrates the potential of such methods in the detection and
      enumeration of respiratory bacteria.

PMID- 17439540
TI  - SLCO1B1 521T-->C functional genetic polymorphism and lipid-lowering efficacy of
      multiple-dose pravastatin in Chinese coronary heart disease patients.
AB  - AIMS: Pravastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitor, which is widely used both in primary and secondary prevention of
      coronary heart disease (CHD). Pravastatin is not subject to metabolism by
      cytochrome P450s, but it is actively transported from blood into target tissues
      (e.g. hepatocytes in the liver) by the organic anion transporting polypeptide 1B1
      (OATP1B1), encoded by SLCO1B1. The aim of the present study was to evaluate the
      impact of SLCO1B1 521T-->C (Val174Ala) functional genetic polymorphism on the
      lipid-lowering efficacy of multiple-dose pravastatin in Chinese patients with
      CHD. METHODS: Forty-five hospitalized patients with CHD prospectively received
      pravastatin as a single-agent therapy (20 mg day(-1) p.o.) for 30 days. Serum
      triglycerides, total cholesterol, low-density lipoprotein-cholesterol and high
      density lipoprotein-cholesterol concentrations were determined before and after
      pravastatin treatment. RESULTS: Pravastatin treatment significantly decreased
      plasma lipids in all patients (P < 0.001). Importantly, we showed an attenuated
      pravastatin pharmacodynamic effect on total cholesterol in patients with 521TC
      heterozygote genotype (from 5.52 +/- 0.51 mmol l(-1) to 4.70 +/- 0.35 mmol l(-1),
      % change -14.5 +/- 6.6%, N = 9) compared with 521TT homozygote genotype (from
      5.47 +/- 1.15 mmol l(-1) to 4.21 +/- 0.89 mmol l(-1), % change -22.4 +/- 10.3%, N
      = 36) (mean +/- SD, P = 0.03, two-tailed test with alpha set at 5%). SLCO1B1 521T
      ->C functional polymorphism did not significantly influence pravastatin
      pharmacodynamics on other plasma lipids (P > 0.05). CONCLUSIONS: The 521T-->C
      polymorphism of SLCO1B1 appears to modulate significantly the total cholesterol
      lowering efficacy of pravastatin in Chinese patients with CHD. Further studies
      are warranted to determine the extent to which SLCO1B1 genetic variation may
      contribute to resistance to pravastatin in Asian patients treated with standard
      doses of pravastatin.

PMID- 17439542
TI  - Helicobacter callitrichis sp. nov., a novel Helicobacter species isolated from
      the feces of the common marmoset (Callithrix jacchus).
AB  - A slowly growing microaerophilic Helicobacter species was isolated from the feces
      of the common marmoset (Callithrix jacchus). This bacterium possessed a pair of
      nonsheathed bipolar flagella, was positive for oxidase, catalase and alkaline
      phosphatase activities, but was negative for gamma-glutamyltranspeptidase and
      urease activity and for nitrate reduction. The bacterium was susceptible to
      nalidixic acid and resistant to cephalotine and did not hydrolyze hippurate. On
      the basis of phenotypic characteristics, 16S rRNA gene sequence analysis and
      whole-cell protein profiles, the isolate represents a new species of the genus
      Helicobacter, for which the name Helicobacter callitrichis sp. nov. is proposed;
      the type strain of the new species is R-204(T) (GenBank accession number
      AY192526).

PMID- 17439543
TI  - Sigma 28 promoter prediction in members of the Gammaproteobacteria.
AB  - A two-step approach was used to predict sigma(28) promoter sequences in a number
      of Gammaproteobacteria. Putative promoters were initially identified upstream of
      motility and chemotaxis genes in test species based on their similarity to the
      Escherichia coli sigma(28) promoter consensus. These sequences were then used to
      generate position specific score matrices that were used iteratively during whole
      genome analyses. The consistent identification of promoter sequences upstream of
      orthologous genes suggested that the predictions were biologically relevant.

PMID- 17439544
TI  - Biosynthesis of open-chain tetrapyrroles in Prochlorococcus marinus.
AB  - Members of the genus Prochlorococcus belong to the most abundant phytoplankton on
      earth. In contrast to other cyanobacteria, Prochlorococcus is characterized by
      divinyl-chlorophyll containing light-harvesting complexes and the lack of
      phycobilisomes. Despite the lack of phycobilisomes, all sequenced genomes of
      Prochlorococcus possess genes that putatively encode enzymes involved in the
      biosynthesis of open-chain tetrapyrrole molecules. Here, biochemical evidence is
      presented indicating that high-light- and low-light-adapted Prochlorococcus
      ecotypes possess genes encoding functional enzymes for the biosynthesis of open
      chain tetrapyrrole molecules. Experiments on recombinant protein as well as
      through complementation studies of a cyanobacterial insertion mutant revealed the
      functionality of the bilin reductases investigated.

PMID- 17439545
TI  - Molecular characterization of MbADGF, a novel member of the adenosine deaminase
      related growth factor in the cabbage armyworm, Mamestra brassicae: the functional
      roles in the midgut cell proliferation.
AB  - To clarify the functional mechanism of the adenosine deaminase-related growth
      factor (ADGF) particularly in the regulation of insect development, the cDNA
      encoding a homologue of ADGF proteins was cloned from the cabbage armyworm,
      Mamestra brassicae, named MbADGF. The purified MbADGF recombinant protein
      stimulated cell proliferation in a dose-dependent manner of SES-MaBr-4 and NIAS
      MaBr-93 cell lines that were derived from fat bodies and haemocytes of M.
      brassicae. The adenosine deaminase activity of MbADGF was detected using
      adenosine and 2'-deoxyadenosine as substrates. Northern analysis demonstrated
      that during the larval development the level of MbADGF in the midgut increased.
      In situ hybridization showed that MbADGF mRNA was expressed in midgut goblet
      cells and in the apical cytoplasm of columnar cells, which suggests that MbADGF
      protein may execute its adenosine deaminase activity at the apical cytoplasm of
      columnar cells to convert adenosine into inosine.

PMID- 17439546
TI  - The nicotinic acetylcholine receptor subunit Mdalpha6 from Musca domestica is
      diversified via post-transcriptional modification.
AB  - Recent studies showed that deletion of a nicotinic acetylcholine receptor (nAChR)
      subunit gene, Dalpha6 in Drosophila melanogaster results in a strain that is
      resistant to spinosad, indicating that Dalpha6 is important for the toxic action
      of this insecticide. To determine if spinosad resistance in house flies was due
      to a mutation(s) of Mdalpha6 (the orthologue of Dalpha6 from house flies), cDNAs
      were cloned and characterized from an insecticide-susceptible and a spinosad
      resistant strain of the house fly, Musca domestica. The cDNAs contain a 1470-bp
      open reading frame encoding 490 amino acid residues, 415-bp 5' untranslated
      region (UTR) and a polymorphic 3'-UTR of approximately 371 bp. The predicted
      mature protein possesses 468 amino acid residues, has the typical features of a
      nAChR alpha subunit and is 97% identical to Dalpha6. Quantitative real-time PCR
      analysis revealed that Mdalpha6 was expressed in the head and the thorax at 1300-
      and 26-fold higher levels, respectively, than in the abdomen. There was no
      difference in the expression level of Mdalpha6 between spinosad-resistant and
      susceptible strains. Ten isoforms arising from alternative splicing were
      characterized, with isoform II being most common. A-to-I RNA editing was examined
      and found at 12 sites: editing at 11 of these sites resulted in an amino acid
      substitution. Mdalpha6 is linked to autosome 1 (spinosad resistance was
      previously shown to be linked to autosome 1). Single nucleotide polymorphisms,
      alternative splicing, mRNA levels and A-to-I RNA editing were compared between
      head and thorax and between insecticide-susceptible and spinosad-resistant
      strains. These comparisons indicate that Mdalpha6 is not responsible for spinosad
      resistance in house flies.

PMID- 17439547
TI  - Melatonin as a potential antihypertensive treatment.
AB  - The number of patients with well-controlled hypertension is alarmingly low
      worldwide and new approaches to treatment of increased blood pressure (BP) are
      being sought. Melatonin has a role in blood pressure regulation. The nighttime
      production of melatonin is found to be reduced in hypertensive individuals.
      Administration of melatonin decreased BP in several animal models of
      hypertension, in healthy men and women, and in patients with arterial
      hypertension. Most promising results were achieved in patients with non-dipping
      nighttime pressure, in which the circadian rhythm of BP variation is disturbed.
      Several potential mechanisms of BP reduction are considered. Melatonin can, via
      its scavenging and antioxidant nature, improve endothelial function with
      increased availability of nitric oxide exerting vasodilatory and hypotensive
      effects. Melatonin seems to interfere with peripheral and central autonomic
      system, with a subsequent decrease in the tone of the adrenergic system and an
      increase of the cholinergic system. Melatonin may act on BP also via specific
      melatonin receptors localized in peripheral vessels or in parts of central
      nervous system participating in BP control. With a large clinical trial using
      melatonin in hypertension treatment, many important questions could be answered,
      such as the dose of melatonin and regimen of its application, the choice of
      patients with greatest possible benefit from melatonin treatment, the potential
      of anti-remodeling effect of melatonin and the interaction of melatonin with
      other antihypertensive drugs.

PMID- 17439548
TI  - Melatonin enhances the rewarding properties of morphine: involvement of the
      nitric oxidergic pathway.
AB  - Melatonin has different interactions with opioids including the enhancement of
      the analgesic effects of morphine and also reversal of tolerance and dependence
      to morphine. The present study assessed the effect of melatonin on morphine
      reward in mice using a conditioned place preference (CPP) paradigm. Our data
      showed that subcutaneous administration of morphine (1-7.5 mg/kg) significantly
      increased the time spent in the drug-paired compartment in a dose-dependent
      manner. Intraperitoneal (i.p.) administration of melatonin (1-40 mg/kg) alone did
      not induce either CPP or conditioned place aversion (CPA), while the combination
      of melatonin (5-20 mg/kg) and sub-effective dose of morphine (0.5 mg/kg) led to
      rewarding effect. We further investigated the involvement of the nitric oxidergic
      pathway in the enhancing effect of melatonin on morphine CPP, by a general nitric
      oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). L-NAME (1
      and 5 mg/kg, i.p.) alone or in combination with morphine (0.5 mg/kg) did not show
      any significant CPP or CPA. Co-administration of L-NAME (5 mg/kg) with an
      ineffective combination of melatonin (1 mg/kg) plus morphine (0.5 mg/kg) produced
      significant CPP that may imply the similarity of action of melatonin and L-NAME
      and involvement of the nitric oxidergic pathway in this regard. Our results
      indicate that pretreatment of animals with melatonin enhances the rewarding
      properties of morphine via a mechanism which may involve the nitric oxidergic
      pathway.

PMID- 17439549
TI  - Quantification of the water/lipid affinity of melatonin and a pinoline derivative
      in lipid models.
AB  - This study assessed the location of melatonin (N-acetyl-5-methoxytryptamine) and
      of a pinoline derivative (GWC22) [6-ethyl-1-(3-methoxyphenyl)-2-propyl-1,2,3,4
      tetrahydro-beta-carboline], when present in lipid assemblies such as linoleate
      micelles, phosphatidylcholine liposomes or low density lipoproteins (LDL). The
      efficiency of radical scavenging by these compounds is highly dependent on their
      partitioning between the lipidic and aqueous phases. We determined the proportion
      of melatonin or GWC22 in the aqueous and lipid phases of each system
      (concentrations of the antioxidants ranging between 3 x 10(-5) and 10(-4) m) by
      assaying melatonin or GWC22 by HPLC/UV detection, or by fluorescence for
      melatonin in micelles. Our results show that melatonin and GWC22 were
      preferentially located in the aqueous phase of micelles (68.4% and 59.0%,
      respectively), whereas only 30.5% of melatonin and 39.0% of GWC22 were found in
      the lipid phase. By contrast, in phosphatidylcholine liposomes, both compounds
      were essentially present in the lipid phase (73.5% for melatonin and 79.1% for
      GWC22, versus 25.9% and 19.5% in the aqueous phase, respectively). In the case of
      LDL, 99.9% of the melatonin added was found in the methanol/water extracting
      phase containing phospholipids, unesterified cholesterol and apolipoprotein B100.
      The partitioning of melatonin and GWC22 in linoleate micelles gave new insights
      on the marked protective effect of GWC22 towards radiation-induced lipid
      peroxidation and allowed us to determine more accurately the lower limit values
      of the reaction rate constants of the two molecules studied with lipid peroxyl
      radicals, i.e. k(LOO.+melatonin)) >or= 9.0 x 10(4)m(-1)s(-1) and k(LOO.+GWC22)
      >or= 3.5 x 10(5)m(-1)s(-1).

PMID- 17439550
TI  - Increased vascular permeability and nitric oxide production in response to
      hypoxia in the pineal gland.
AB  - This study examined the factors that may be involved in altering the function of
      pineal gland in hypoxic conditions. Adult Wistar rats were subjected to hypoxia
      and the pineal gland was examined for the mRNA and protein expression of hypoxia
      inducible factor-1alpha (HIF-1alpha), vascular endothelial growth factor (VEGF),
      endothelial, neuronal and inducible nitric oxide synthase (eNOS, nNOS, iNOS) at 3
      hr-14 days after hypoxic exposure by real time reverse transcription-polymerase
      chain reaction, Western blotting and immunohistochemistry. Upregulated mRNA and
      protein expression of HIF-1alpha, VEGF, eNOS, nNOS and iNOS was observed in
      response to hypoxia. VEGF concentrations as determined by enzyme immunoassay and
      nitric oxide (NO) production measured by colorimetric assay were significantly
      higher after hypoxic exposure when compared with the controls. Melatonin content
      of the pineal gland, as determined by ELISA, was significantly reduced after the
      hypoxic exposure. Dilated blood vessels expressing eNOS were observed in hypoxic
      rats. Cells immunoreactive for VEGF were identified as the astrocytes whereas
      those immunoreactive for iNOS were pinealocytes and macrophages. Our findings
      indicate that excess production of VEGF and NO in pineal gland in response to
      hypoxia may be involved in increased vascular permeability as evidenced by an
      enhanced leakage of rhodamine isothiocyanate (RhIC). The increased vascular
      permeability may allow free access of serum-derived substances in the pineal
      gland that may affect the secretory function of the pinealocytes. Administration
      of exogenous melatonin may be beneficial as it reduced VEGF concentration and NO
      production significantly in hypoxic rats, and leakage of RhIC was concomitantly
      reduced.

PMID- 17439551
TI  - Melatonin and type 2 diabetes - a possible link?
AB  - The aim of the present study was to determine the existence of melatonin membrane
      receptors and to examine the mRNA expression of nuclear orphan receptors in human
      pancreatic tissue, in an effort to explain differences between type 2 diabetic
      and metabolically healthy patients. Molecular and immunocytochemical
      investigations established the presence of the melatonin membrane receptors MT1
      and MT2 in human pancreatic tissue and, notably, also in the islets of
      Langerhans. Results of a calculation model to determine mRNA expression ratios,
      as well as subjective analysis of immunoreactions, showed elevated MT1 receptor
      expression in comparison with MT2 expression. mRNA transcript levels of melatonin
      receptors appeared to be significantly higher in type 2 diabetic patients than in
      a control group. An upregulation of receptor expression in type 2 diabetic
      patients was also observed in immunocytochemical investigations. In addition,
      transcripts of the nuclear orphan receptors RORalpha, RZRbeta, RORgamma and
      RevErbalpha were detected in human pancreatic tissue and islets. In correlation
      with membrane melatonin receptors, data indicate increased mRNA expression levels
      of RORalpha, RZRbeta, and RORgamma in type 2 diabetic patients. Thus, our data
      demonstrate the existence of the melatonin membrane receptors MT1 and MT2 as well
      as mRNA expression of nuclear orphan receptors in human pancreatic tissue, with
      upregulated expression levels in type 2 diabetic patients.

PMID- 17439552
TI  - Melatonin treatment reduces the severity of experimental Trypanosoma cruzi
      infection.
AB  - Prior studies show that melatonin enhances the immune response. This study
      investigated the possible therapeutic effects of melatonin during the course of
      Trypanosoma cruzi infection. T. cruzi-infected male Wistar rats were orally
      treated with 5 mg/kg body weight/day of melatonin. Animals treated with melatonin
      showed a significant reduction in the number of blood trypomastigotes during the
      acute phase of infection compared with untreated animals (P<0.05). A significant
      increase in leucocytes numbers during the peak of parasitaemia was also observed
      (P<0.05). Moreover, both prior and concomitant treatment with melatonin increased
      interleukin-2 levels, especially 9 days postinfection (P<0.05). Histopathological
      observations of heart tissue revealed that melatonin administration also resulted
      in fewer and smaller amastigote burdens, and less inflammatory infiltrate and
      tissue disorganization, indicating a reduced parasitism of this tissue. These
      results show that melatonin is effective in controlling parasite replication and
      suggest that melatonin might serve as an effective therapeutic agent in the
      treatment of American trypanosomiasis.

PMID- 17439553
TI  - Protective effect of melatonin in acetic acid induced colitis in rats.
AB  - Possible protective effects of exogenous melatonin on colonic inflammation were
      studied in rats. Colitis was induced by intracolonic (i.c.) instillation of 4%
      acetic acid (AA) and the resulting injury was assessed after 1 and 48 hr. Diffuse
      hyperemia and bleeding with erosions and ulcerations were observed in the colons
      of vehicle-treated rats. Melatonin administered in doses of 5 and 10 mg/kg
      reduced significantly the extent of gross mucosal damage after intraperitoneal as
      well as i.c. dosing. The inflammation induced increase in colonic wet weight was
      also reduced by melatonin treatment. In the early phase of colonic inflammation
      (60 min), melatonin partly prevented the decrease of reduced glutathione (GSH)
      content and limited lysosomal enzyme, N-acetyl-glucosaminidase and cathepsin D,
      activities induced by AA, with no changes in proteins or acid phosphatase
      activity. Increase of myeloperoxidase activity (MPO) caused by colonic
      inflammation was prevented by melatonin given i.c. As observed 48 hr after AA
      exposure, there was no difference between the effect of vehicle and melatonin on
      the content of GSH. Colitis did not influence the melatonin content of the colon.
      After administration of exogenous melatonin, plasma, pineal and gut melatonin
      tended to increase. The results indicate that melatonin participates in various
      defense mechanisms against colonic inflammatory processes by preserving the
      important endogenous antioxidant reserve of GSH, by preventing lysosomal enzyme
      disruption, by inhibiting enhanced MPO activity, thus reducing the extent of
      colonic damage, mainly in the early phase of colitis.

PMID- 17439554
TI  - NO-donor melatonin derivatives: synthesis and in vitro pharmacological
      characterization.
AB  - Numerous studies document that melatonin possesses a broad-spectrum antioxidant
      activity. It traps a number of reactive oxygen species (ROS) such as hydroxyl and
      peroxyl radicals, singlet oxygen and hypochlorous acid. It also inhibits
      peroxynitrite-induced reactions. It is known that atherosclerosis progression
      involves ROS-induced oxidation of low-density lipoproteins in sub-endothelial
      space and the depletion of nitric oxide (NO) in blood vessels, as well as a
      decreased sensitivity of the vessels to the actions of NO. Considering this, a
      series of new NO-donor antioxidants were designed and synthesized by joining
      melatonin with NO-donor nitrooxy and furoxan moieties as polyvalent agents
      potentially useful for the treatment of cardiovascular diseases involving
      atherosclerotic vascular changes. The in vitro antioxidant properties of the
      resulting products were assessed in the thiobarbituric acid reactive substances
      assay (TBARS), the ABTS(+.) as well as in the alkaline phosphatase (ALP) assay.
      The antioxidant capacities of NO-donor melatonins to inhibit lipoperoxidation
      (TBARS-IC(50)) was predominantly dependent on their lipophilicity, and therefore
      on their partitioning process into membranes. On the other hand, their comparable
      capacity to inhibit protein oxidation (ALP-IC(50)) was independent of their
      lipophilicity and was consistent with their similar ability to participate in
      electron transfer reactions. All the NO-donor melatonins were also evaluated for
      their ability to relax rat aorta strips precontracted with 1 microM
      phenylephrine. Finally, binding affinities and intrinsic activity studies,
      carried out at MT(1) and MT(2) receptor subtypes, showed a rather complex picture
      in need of further investigation.

PMID- 17439555
TI  - AFMK, a melatonin metabolite, attenuates X-ray-induced oxidative damage to DNA,
      proteins and lipids in mice.
AB  - Antioxidant function of melatonin is well established. However, N(1)-acetyl-N(2)
      formyl-5-methoxykynuramine (AFMK), a melatonin metabolite is a sparingly
      investigated biogenic amine, especially in relation to its in vivo antioxidant
      function. We have evaluated the oxidative damage to biomolecules (DNA, protein
      and lipid) induced by X-irradiation in C57BL mice and the prophylactic action of
      AFMK. The extent of DNA damage was analyzed by single-cell gel electrophoresis in
      cerebral cortex and serum 8-hydroxydeoxyguanosine (8-OHdG) levels by enzyme
      linked immunosorbent assay. Oxidative modification of protein and lipid was
      measured in the terms of carbonyl content and 4-HAE + MDA (4-hydroxyalkenal +
      malondialdehyde) status of brain cortex. Radiation exposure dramatically
      augmented the level of 8-OHdG in serum as well as DNA migration in the comet
      tail. AFMK pretreatment significantly inhibited DNA damage. In addition,
      radiation-induced augmentation of protein carbonyl content and HAE + MDA was
      ameliorated by AFMK pretreatment. Whole-body exposure of mice to X-irradiation
      also reduced the level of brain sulfhydryl contents (protein-bound sulfhydryl,
      total sulfhydryl, and nonprotein sulfhydryl) which were significantly protected
      by AFMK. Radiation-induced decline in the total antioxidant capacity of plasma
      was significantly reversed in AFMK pretreated mice. Moreover, AFMK showed a very
      high level of in vitro hydroxyl radical scavenging potential which was measured
      by an electron spin resonance (ESR) study of the 2-hydroxy-5,5-dimethyl-1
      pyrrolineN-oxide (DMPO-OH) adduct. IC(50) values resulting from ESR analysis was
      338.08 nm. The present study indicate that AFMK is a potent antioxidant in both
      in vivo and in vitro systems.

PMID- 17439556
TI  - Chronic administration of melatonin reduces cerebral injury biomarkers in SAMP8.
AB  - Certain effects of melatonin on senescence were investigated. The experimental
      model used was 10-month-old senescence-accelerated mouse prone 8 (SAMP8). The
      mice in the experiment were administered melatonin (10 mg/kg) from the age of 1
      month. Results showed that chronic administration of melatonin decreased cell
      loss in the cerebral cortex and reduced oxidative damage in protein and lipids.
      There are several studies suggesting that the activation of the cdk5/p35 pathway
      at its cleavage to cdk5/p25 may play a role in hyperphosphorylation of tau during
      aging and neurodegenerative diseases. Melatonin not only reduced the cerebral
      aging disturbances, but also prevented tau hyperphosphorylation present in the
      experimental model used in this study. Melatonin reduced cdk5 expression, as well
      as the cleavage of p35 to p25. The other tau kinase studied, GSK3beta, showed a
      reduction in this activity in comparison with SAMP8 nontreated SAMP8. These data
      indicate that melatonin possesses neuroprotective properties against cerebral
      damage gated to senescence. Moreover, these data suggest that the cdk5/GSKbeta
      signaling cascade has a potential role as a target for neurodegenerative diseases
      related to aging.

PMID- 17439557
TI  - Melatonin prevents the estrogenic effects of sub-chronic administration of
      cadmium on mice mammary glands and uterus.
AB  - Cadmium (Cd) is a heavy metal classified as a human carcinogen. Occupational
      exposure, dietary consumption and cigarette smoking are sources of Cd
      contamination. Cd-induced carcinogenicity depends on its oxidative and estrogenic
      actions. A possible role of Cd in breast cancer etiology has been recently
      suggested. Melatonin, because of its antioxidant and antiestrogenic properties
      could counteract the toxic effects of this metalloestrogen. Our aim was both to
      determine the effects of relevant doses of Cd on mice mammary glands and uterus
      and to test whether melatonin would counteract its effects. Female mice of
      different ages and estrogenic status (prepuberal, adult intact, adult
      ovariectomized) were treated with CdCl(2) (2-3 mg/kg, i.p.), melatonin (10
      microg/mL in drinking water), CdCl(2) + melatonin, or diluents. Whereas in
      prepuberal animals Cd disturbs mammary ductal growth and reduces the number of
      terminal end buds, in adults, regardless of the steroidal milieu, Cd exerts
      estrogenic effects on mammary glands, increasing lobuloalveolar development and
      ductal branching. Uterine weight also increased as a result of Cd treatment. The
      effects of Cd are partially inhibited by melatonin. In adult ovariectomized mice,
      Cd concentration in blood of animals treated with CdCl(2) + melatonin was lower
      than in mice receiving only Cd; the opposite effects were found in non-castrated
      animals. As Cd mimics the effect of estrogens, the high incidence of breast
      cancer in tobacco smokers and women working in industries related with Cd could
      be explained because of the properties of this metal. The effects of melatonin
      point to a possible role of this indoleamine as a preventive agent for
      environmental or occupational Cd contamination.

PMID- 17439558
TI  - Melatonin influences the proliferative and differentiative activity of neural
      stem cells.
AB  - Though melatonin has a wide variety of biological functions, its effects on the
      neural stem cells (NSCs) is still unknown. In this study, we examined the effects
      of melatonin at either physiological (0.01-10 nm) or pharmacological
      concentrations (1-100 microM) on the proliferation and neural and astroglial
      differentiation of NSCs derived from the mouse embryo striatum using an in vitro
      culture system. We found that melatonin at pharmacological concentrations, but
      not at physiological concentrations, suppressed epidermal growth factor (EGF)
      stimulated NSC proliferation (increment of viable cells, DNA synthesis and
      neurosphere formation) in a concentration-dependent manner. Furthermore,
      treatment with melatonin at a pharmacological concentration during the
      proliferation period facilitated 1% FBS-induced neural differentiation of NSCs
      without affecting the astroglial differentiation. In contrast, the treatment with
      melatonin at pharmacological concentrations during the differentiation period
      decreased the neural differentiation of the NSCs. As with melatonin, MCI-186, an
      antioxidant, suppressed EGF-stimulated NSC proliferation and facilitated the
      subsequent neural differentiation of NSCs. These results suggest that melatonin
      exerts potent modulatory effects on NSC functions including the suppression of
      the proliferation and facilitation of neuronal differentiation, likely via its
      antioxidant activity. As neurogenesis is thought to play an important role in
      ameliorating the deficit in neurodegenerative diseases, melatonin might be
      beneficially used for the treatment diseases such as cerebral infarction.

PMID- 17439559
TI  - Melatonin reduces oxidative stress because of tooth removal.

PMID- 17439561
TI  - Trials and tribulations of operative vaginal delivery.

PMID- 17439562
TI  - Could a cervical occlusion suture be effective at improving perinatal outcome?
AB  - Cervical weakness and infection have long been regarded as major causes of
      preterm birth. Cervical cerclage has been used extensively to reduce the risk of
      preterm birth arising as a result of cervical weakness, but increasing evidence
      suggests that the cervix plays more than just a mechanical role. Immunological
      function of the cervix and mucus plug is thought to be important in minimising
      the ingress of microbes, which can lead to chorioamnionitis and rupture of the
      amniotic membranes. In this review, we examine the background of traditional
      cervical cerclage and introduce the concept of the occlusion suture and its
      potential benefit in reducing the risk of recurrent preterm prelabour rupture of
      membranes.

PMID- 17439563
TI  - Does methotrexate confer a significant advantage over misoprostol alone for early
      medical abortion? A retrospective analysis of 8678 abortions.
AB  - OBJECTIVE: The objective of this study was to compare efficacy for four medical
      abortion regimens used in one clinic setting: (1) misoprostol alone, (2) oral
      methotrexate + buccal misoprostol, (3) oral methotrexate + vaginal misoprostol,
      and (4) intramuscular methotrexate + vaginal misoprostol. DESIGN: Retrospective
      analysis of data from clinical records. SETTING: An anonymous women's health
      centre in Latin America, providing medical abortion services since 2001 in a
      highly restrictive setting. POPULATION: A total of 8678 women with gestations <56
      days, who sought a medical abortion between April 2002 and December 2004.
      METHODS: Chi-square test was performed to compare patient characteristics by
      abortion outcome (success/failure). The impact of selected variables on method
      success was explored through logistic regression. A second regression analysis
      was conducted with a subsample (n = 4022), for which data on parity and previous
      abortion(s) were available. MAIN OUTCOME MEASURE: Abortion outcome
      (success/failure) at 2-week follow up. RESULTS: Success rates for the three
      methotrexate regimens ranged from 81.7 to 83.5% and did not differ significantly;
      misoprostol-alone regimen had a success rate of 76.8%. Efficacy was significantly
      higher for the three combined methotrexate regimens compared with misoprostol
      alone and remained so in the multivariate model (OR = 1.35). In the final
      regression, lower gestational age, being nulliparous, and having no previous
      abortions were positively correlated with method success. CONCLUSIONS: In this
      real-use setting, methotrexate appears to confer a significant advantage over
      misoprostol alone for early medical abortion. This finding is important for
      settings where mifepristone remains unavailable. Additional factors such as
      gestational age limits and patient preference should be considered in regimen
      selection.

PMID- 17439564
TI  - The effect of hysterectomy or levonorgestrel-releasing intrauterine system on
      sexual functioning among women with menorrhagia: a 5-year randomised controlled
      trial.
AB  - OBJECTIVE: To compare among women with menorrhagia the effect of hysterectomy or
      levonorgestrel-releasing intrauterine system (LNG-IUS) on sexual functioning.
      DESIGN: A randomised controlled trial. SETTING: Five university hospitals in
      Finland. SAMPLE: A total of 236 women, aged 35-49 years. METHODS: Of the women,
      117 were treated by hysterectomy and 119 by LNG-IUS. MAIN OUTCOME MEASURES:
      Sexual functioning was evaluated by modified McCoy sexual scale at baseline and
      at 6 months, 12 months, and 5 years after initiation of treatment (hysterectomy
      or application of LNG-IUS). RESULTS: Among women treated by hysterectomy, sexual
      satisfaction increased and sexual problems decreased. Among LNG-IUS users,
      satisfaction with partner decreased. In addition to treatment modality (P =
      0.02), estrogen therapy (P = 0.01), smoking (P = 0.001), night sweats (P = 0.03),
      vaginal dryness (P = 0.04), hot flushes (P = 0.01), and having someone to ask for
      advice (P = 0.03) and to share worries (P = 0.01) explained changes in sexual
      functioning. CONCLUSIONS: Among women with menorrhagia, hysterectomy improves
      sexual functioning, whereas LNG-IUS does not have such a positive effect.

PMID- 17439565
TI  - A comparison of women's, providers' and ultrasound assessments of pregnancy
      duration among termination of pregnancy clients in South Africa.
AB  - OBJECTIVE: To compare providers' and women's estimates of duration of pregnancy
      with ultrasound estimates for determining medical abortion eligibility. DESIGN:
      Cross-sectional study. SETTING: Public termination of pregnancy (TOP) services in
      three provinces. SAMPLE: A total of 673 women attending the above services for
      TOP. METHODS: Women participating in a medical abortion feasibility study in
      South Africa provided estimates of pregnancy duration and date of last menstrual
      period (LMP). Each woman also had clinical and ultrasound exams. We compared
      estimates using the four methods, calculating the proportion of women in the
      'caution zone' (< or = 8 weeks gestation by woman or provider estimate and > 8
      weeks by ultrasound). MAIN OUTCOME MEASURES: Mean gestational age by each method;
      difference between provider and LMP estimates and ultrasound estimates; and
      percentage of women in the 'caution zone'. RESULTS: Women's estimates of
      pregnancy duration were 19 days fewer than ultrasound estimates (95% CI = -27 to
      63). Mean provider- and LMP-based estimates were two (95% CI = -30 to 35) and
      less than one day(s) (95% CI = -46 to 51) fewer than ultrasound estimates.
      Comparing provider and ultrasound estimates, 15% of women were in the 'caution
      zone'; this fell to 12% if estimates of 9 weeks or fewer were considered
      acceptable. CONCLUSIONS: Provider estimates of gestational age were sufficiently
      accurate for determining eligibility for medical abortion. LMP-based estimates
      were also accurate on average, but included more extreme differences from
      ultrasound estimates. Medical abortion could be provided in TOP facilities
      without ultrasound or with ultrasound on referral.

PMID- 17439566
TI  - Haemodynamic changes in the second half of pregnancy: a longitudinal, noninvasive
      study with thoracic electrical bioimpedance.
AB  - OBJECTIVE: Maternal cardiovascular adaptations to pregnancy are necessary for an
      adequate fetomaternal circulation. However, the time course of physiological
      haemodynamic changes during the second half of pregnancy remains unclear. Various
      methods, invasive and noninvasive, are described to measure these changes. The
      thoracic electrical bioimpedance (TEB) technique is a method which is especially
      suitable to measure haemodynamic changes over time. The aim of the study was to
      determine both individual and group trends of haemodynamic changes in healthy
      pregnant women during the second half of pregnancy by means of TEB. Outcome
      variables are heart rate (HR), stroke volume (SV), cardiac output (CO) and blood
      pressure. DESIGN: Longitudinal study. SETTING: Outpatient antenatal care clinic
      of university hospital. POPULATION: A total of 22 healthy nonsmoking women with
      an uncomplicated singleton pregnancy and without pre-existing vascular disorders
      were invited. METHODS: TEB and blood pressure measurements were performed at each
      regular visit from about 24 weeks of gestation through term age. MAIN OUTCOME
      MEASURES: Trends were calculated with the random effects model. RESULTS: Data
      obtained from 19 women were analysed, with a median of eight (range 3-11)
      measurements. HR showed a linear increase (P < 0.0005) and a quadratic trend (P <
      0.0005). SV decreased linearly (P = 0.046), without a quadratic course. CO
      remained stable over time. CONCLUSION: During the second half of physiological
      pregnancy, significant trends could be determined. An increase in HR, a decrease
      in SV, a stable CO and an increase in systolic and diastolic blood pressures were
      found.

PMID- 17439568
TI  - Neuropsychological outcome of children with asymmetric ventricles or unilateral
      mild ventriculomegaly identified in utero.
AB  - DESIGN: To assess the neuropsychological outcome of children with asymmetric
      ventricles and unilateral ventriculomegaly identified in utero. SETTING: Fetal
      neurology clinic. POPULATION: We assessed 21 children with asymmetric ventricles
      (group 1) and 20 children with unilateral ventriculomegaly (group 2) identified
      in utero and compared them with a group of 20 children with symmetric ventricles
      using a formal neuropsychological tool: the Bayley Scale of Infant Development II
      (BSID-II). MAIN OUTCOME MEASURES: The group of children with unilateral
      ventriculomegaly scored significantly lower than the control group on the mental
      developmental index (MDI) and on the behaviour rating scale (BRS) but not on the
      psychomotor index. The group of children with asymmetric ventricles did not
      differ significantly from the control group on either the MDI or psychomotor
      developmental index but differed from the latter on the BRS. Fifteen percent of
      the children in the asymmetric ventriculomegaly group performed two SDs below
      average compared with 4% of children in the asymmetrical ventricles group and
      none of the control. CONCLUSION: Our results indicate that prenatally observed
      unilateral ventriculomegaly is a significant risk factor for developmental delay.
      The mental and motor outcome of children with asymmetric ventricles is similar to
      that of the control group, but these children are at a significant risk for
      behavioural abnormalities.

PMID- 17439567
TI  - Safety of benzyl benzoate lotion and permethrin in pregnancy: a retrospective
      matched cohort study.
AB  - OBJECTIVE: To assess the safety of benzyl benzoate lotion (BBL) and permethrin,
      topical treatments for scabies, during pregnancy. DESIGN: A retrospective
      controlled cohort study. POPULATION: Refugee and migrant women attending
      antenatal clinics (ANC) on the Thai-Burmese border between August 1993 and April
      2006. METHODS: Women treated with either BBL (25%) or permethrin (4%) were
      identified from a manual search of antenatal records. Each case of scabies was
      matched with four scabies-free controls for gravidity, age, smoking status,
      malaria, period of treatment and gestational age at treatment. Conditional
      Poisson regression was used to estimate risk ratios for outcomes of pregnancy
      (proportion of abortions, congenital abnormalities, neonatal deaths, stillbirths
      and premature babies), mean birthweight and estimated median gestational age, for
      scabies and scabies-free women, independently for BBL and permethrin. RESULTS:
      There were no statistically significant differences in pregnancy outcomes between
      women who were treated with either BBL (n = 444) compared with their matched
      controls (n = 1,776) or permethrin (n = 196) treated women and their matched
      controls (n = 784). Overall, only 10.9% (n = 66) of treatments were in the first
      trimester. Retreatment rates were higher with BBL 16.4%, than permethrin 9.7%, P
      = 0.038. Scabies was more common during cooler periods. CONCLUSION: We found no
      evidence of adverse effects on pregnancy outcome due to topical 25% BBL or 4%
      permethrin.

PMID- 17439569
TI  - The impact of a trial of instrumental delivery in theatre on neonatal outcome.
AB  - OBJECTIVE: To observe the effect of a trial of instrumental delivery in theatre
      on outcome for mother and baby. DESIGN: A prospective observational study.
      METHODS: Relevant maternal and neonatal data were collected for all instrumental
      deliveries of singleton viable pregnancies delivered over a three month period.
      POPULATION: Two hundred and twenty nine consecutive deliveries conducted by
      ventouse or forceps because of fetal distress or dystocia. SETTING: The maternity
      unit of a teaching hospital delivering around 6000 women annually. MAIN OUTCOME
      MEASURES: The decision-to-delivery intervals (DDI), mode of delivery and neonatal
      condition at birth. RESULTS: Sixty (26%) deliveries were managed as a trial in
      theatre, 46 (77%) because of prolonged second stage, with malposition being a
      factor in 39, and 14 (23%) because of fetal distress. The mean +/- SD DDI for
      these 60 deliveries was 59.2 +/- 20.4 minutes (median 58 minutes) compared with
      21.2 +/- 9.0 minutes (median 20 minutes) for 169 delivered in the labour room (P
      < 0.0001). Of these 169 deliveries, 168 were delivered within 46 minutes and 1
      delivered by caesarean section at 60 minutes. Nine women (13%) ultimately
      delivered by caesarean section, eight following a trial in theatre; in seven,
      there was malposition. Deliveries following a trial had slightly less favourable
      cord blood gas results. CONCLUSIONS: Trial of instrumental delivery takes two to
      three times longer than delivery in the labour room; fetal malposition was the
      major indication for the trial of instrumental delivery and reason for failed
      delivery. Adopting the recent guidelines of the Royal College of Obstetricians
      and Gynaecologists, at least 107 (47%) should have been managed as a trial in
      theatre. The added delay in delivery could be damaging to an already hypoxic
      fetus, and the use of a trial should be individually assessed.

PMID- 17439570
TI  - The diagnostic accuracy of external pelvimetry and maternal height to predict
      dystocia in nulliparous women: a study in Cameroon.
AB  - OBJECTIVE: In many developing countries, most women deliver at home or in
      facilities without operative capability. Identification before labour of women at
      risk of dystocia and timely referral to a district hospital for delivery is one
      strategy to reduce maternal and perinatal mortality and morbidity. Our objective
      was to assess the prediction of dystocia by the combination of maternal height
      with external pelvimetry, and with foot length and symphysis-fundus height.
      DESIGN: A prospective cohort study. SETTING: Three maternity units in Yaounde,
      Cameroon. POPULATION: A total of 807 consecutive nulliparous women at term who
      completed a trial of labour and delivered a single fetus in vertex presentation.
      METHODS: Anthropometric measurements were recorded at the antenatal visit by a
      researcher and concealed from the staff managing labour. After delivery, the
      accuracy of individual and combined measurements in the prediction of dystocia
      was analysed. MAIN OUTCOME MEASURES: Dystocia, defined as caesarean section for
      dystocia; vacuum or forceps delivery after a prolonged labour (>12 hours); or
      spontaneous delivery after a prolonged labour associated with intrapartum death.
      RESULTS: Ninety-eight women (12.1%) had dystocia. The combination of a maternal
      height less than or equal to the 5th percentile or a transverse diagonal of the
      Michaelis sacral rhomboid area less than or equal to the 10th percentile resulted
      in a sensitivity of 53.1% (95% CI 42.7-63.2), a specificity of 92.0% (95% CI 89.7
      93.9), a positive predictive value of 47.7% (95% CI 38.0-57.5) and a positive
      likelihood ratio of 6.6 (95% CI 4.8-9.0), with 13.5% of all women presumed to be
      at risk. Other combinations resulted in inferior prediction. CONCLUSION: The
      combination of the maternal height with the transverse diagonal of the Michaelis
      sacral rhomboid area could identify, before labour, more than half of the cases
      of dystocia in nulliparous women.

PMID- 17439571
TI  - Pregnancy outcome in Factor XI deficiency: incidence of miscarriage, antenatal
      and postnatal haemorrhage in 33 women with Factor XI deficiency.
AB  - Pregnancy complications in women with Factor XI deficiency were assessed in this
      retrospective analysis. All nonnulliparous women registered with Factor XI
      deficiency in the East Midlands region were included. Each woman was classified
      into 'bleeder' or 'nonbleeder'. Rates of antenatal and postnatal bleeding and
      miscarriage rate were recorded. A total of 33 women had 105 pregnancies.
      Pregnancy and delivery was uneventful in 70% of the cases. Postpartum haemorrhage
      (PPH) appears increased in women with a 'bleeding' phenotype with a highly
      significant difference between 'bleeders' and 'nonbleeders' (relative risk [RR]
      7.2; CI 1.99-25.9). Miscarriage rate appeared unchanged. We conclude that PPH is
      increased in a subgroup with a bleeding phenotype. Larger studies are needed to
      define the underlying factors.

PMID- 17439572
TI  - Cervical occlusion in women with cervical insufficiency: protocol for a
      randomised, controlled trial with cerclage, with and without cervical occlusion.
AB  - OBJECTIVE: To evaluate the effect of double cerclage compared with a single
      cerclage. DESIGN: Randomised, controlled multicentre trial. SETTING: Ten
      different countries are participating with both secondary and tertiary centres.
      The countries participating are Denmark, Sweden, Germany, United Kingdom, Spain,
      South Africa, Australia and India. This gives both a broad spectrum of diversity
      global and local. We expect a total of 242 women enrolled per year. POPULATION:
      Prophylactic study: 1. History of cervical incompetence/insufficiency. (Delivery
      15 to <36 weeks.) 2. Congenital short cervix (secondary to maternal
      administration of diethyl stilbestrol) or traumatic/surgical damage rendering the
      vaginal approach difficult (e.g. conisation). 3. Cervical suture applied in
      previous pregnancy, successful outcome. 4. Previous failed cerclage. Therapeutic
      study: 5. Secondary cerclage: Short cervix, without the membranes being exposed
      to the vagina. 6. Tertiary cerclage: Short cervix, membranes exposed to the
      vagina. Observational study: Eligible women who refuse to be randomised will
      participate in an observational study. 7. Repeat/requested cervical occlusion.
      METHODS: The women will be randomised between a single (vaginal or abdominal) and
      a double cerclage. The cervical cerclage (McDonald or Shirodkar) as well as the
      abdominal suture will be performed with the same material and technique normally
      used by the participating department. Those randomised to the double cerclage
      will have their external os closed with a continuous nylon 2-0/3-0 suture, in
      addition to the standard single cerclage. Local guidelines concerning
      antibiotics, Heparin, bed rest, tocolytics etc. are followed and recorded in the
      follow-up form. MAIN OUTCOME MEASURES: Primary endpoint is take home baby rate.
      The secondary endpoints are gestational age at delivery, incidence of preterm
      birth (<34+0 days) and number of days in neonatal unit.

PMID- 17439574
TI  - Improving the existing diagnostic strategy by accounting for characteristics of
      the women in the diagnostic work up for postmenopausal bleeding.

PMID- 17439575
TI  - Diminishing sample size and not flattening of the learning curve was responsible
      for the observed results.

PMID- 17439576
TI  - Association between lactate in vaginal fluid and time to spontaneous onset of
      labour from women with suspected prelabour rupture of the membranes.

PMID- 17439579
TI  - Incidence of upper genital tract occlusion following microwave endometrial
      ablation (MEA).

PMID- 17439582
TI  - Intravenous versus oral iron therapy for postpartum anaemia.

PMID- 17439583
TI  - Virtual reality simulation training can improve technical skills during
      laparoscopic salpingectomy for ectopic pregnancy.

PMID- 17439584
TI  - Consensus on the management of obstetric cholestasis. National UK survey.

PMID- 17439585
TI  - Relationship between haemoglobin change and estimated blood loss after delivery.

PMID- 17439588
TI  - In situ hydrogen consumption kinetics as an indicator of subsurface microbial
      activity.
AB  - There are few methods available for broadly assessing microbial community
      metabolism directly within a groundwater environment. In this study, hydrogen
      consumption rates were estimated from in situ injection/withdrawal tests
      conducted in two geochemically varying, contaminated aquifers as an approach
      towards developing such a method. The hydrogen consumption first-order rates
      varied from 0.002 nM h(-1) for an uncontaminated, aerobic site to 2.5 nM h(-1)
      for a contaminated site where sulfate reduction was a predominant process. The
      method could accommodate the over three orders of magnitude range in rates that
      existed between subsurface sites. In a denitrifying zone, the hydrogen
      consumption rate (0.02 nM h(-1)) was immediately abolished in the presence of air
      or an antibiotic mixture, suggesting that such measurements may also be sensitive
      to the effects of environmental perturbations on field microbial activities.
      Comparable laboratory determinations with sediment slurries exhibited hydrogen
      consumption kinetics that differed substantially from the field estimates.
      Because anaerobic degradation of organic matter relies on the rapid consumption
      of hydrogen and subsequent maintenance at low levels, such in situ measures of
      hydrogen turnover can serve as a key indicator of the functioning of microbial
      food webs and may be more reliable than laboratory determinations.

PMID- 17439589
TI  - Utilising multichannel intraluminal impedance for diagnosing GERD: a review.
AB  - The diagnosis of gastroesophageal reflux is sometimes challenging, especially
      when symptoms are unresponsive to high-dose acid suppression. With the advent of
      new technology it is possible to detect and quantify nonacid or weakly acidic
      reflux. Multichannel intraluminal impedance (MII), introduced over 10 years ago,
      is gaining popularity as a reflux detection tool. The ability to detect nonacid
      or weakly acidic reflux events, aerophagia, and to discern true reflux events
      from swallows could make it more a powerful tool than pH detection alone. This is
      a review of the role of MII as it pertains to the diagnosis of GERD and related
      disorders. Studies done on normal subjects and in GERD reveal that nonacid or
      weakly acidic reflux occurs frequently. Several studies have been published that
      document types and frequency or reflux episodes comparing pH to MII. pH
      electrodes fail to detect the majority of nonacid or weakly acidic reflux events.
      MII has revealed nonacid reflux to be less common in untreated GERD subjects than
      in normal subjects. GERD subjects have greater degrees of liquid-type reflux
      events compared to normal subjects who have more gas-type reflux events. In
      treated GERD subjects and normal subjects, proton pump inhibitors do not seem to
      decrease the amount of reflux but render the reflux nonacid or weakly acidic in
      nature. Recently work evaluating atypical symptoms of GERD with MII has been
      published.

PMID- 17439590
TI  - Antireflux stents for palliation of malignant esophagocardial stenosis.
AB  - Placement of self-expanding metal stents (SEMS) for palliation of malignant
      stenoses at the gastroesophageal junction is often associated with stent
      migration and reflux symptoms. SEMS with an antireflux mechanism have been
      developed to overcome the latter problem. The aim of this study was to evaluate
      the safety and efficacy of antireflux Z-stents. Patients with advanced squamous
      cell or adenocarcinoma of the distal esophagus or cardia suffering from dysphagia
      received an antireflux Z-stent. Technical success, complications of the
      procedure, clinical symptoms before and after stent placement, reinterventions
      and survival were recorded. Follow-up was accomplished by patient interviews and
      a standardized questionnaire for primary care physicians. Eighteen consecutive
      patients received an antireflux Z-stent. Seventeen of 18 stents were placed
      technically successful in a single endoscopic procedure. Mean dysphagia score
      improved from 2.2 to 0.6. Four patients (22%) had permanent reflux symptoms, an
      additional nine (50%) were taking proton pump inhibitors on a regular basis. In
      10 patients, a re-intervention was necessary mainly due to dislocation of the
      stent. To ensure adequate nutrition three and two patients received a
      percutaneous gastrostomy and a jejunostomy, respectively. Median survival from
      stent insertion was 54 days (range, 3-201). Although placement of an antireflux Z
      stent is technically feasible, its application is hampered by frequent stent
      migration and insufficient prevention of gastroesophageal reflux. Further
      technical improvements of stents or alternative methods like brachytherapy are
      required for satisfactory palliation of malignant gastroesophageal stenosis.

PMID- 17439591
TI  - Reduction rate of lymph node metastasis as a significant prognostic factor in
      esophageal cancer patients treated with neoadjuvant chemoradiation therapy.
AB  - Tumor regression is used widely as a measure of tumor response following
      radiation therapy or chemoradiation therapy (CRT). In cases of esophageal cancer,
      a different pattern of tumor shrinkage is often observed between primary tumors
      and metastatic lymph nodes (MLNs). Regression of MLNs surrounded by normal tissue
      may be a more direct measure of the response to CRT than regression of a primary
      tumor as exfoliative mechanical clearance does not participate in shrinkage of
      MLNs. In this study we evaluated the significance of the reduction rate (RR) of
      MLNs as a prognostic factor in esophageal cancer patients treated with
      neoadjuvant CRT. Forty-two patients with marked MLNs were selected from 93
      patients with esophageal carcinoma who had received neoadjuvant CRT. The RRs of
      the primary tumor and the MLNs were calculated from computed tomography scans. In
      20 patients, surgical resection was carried out following CRT. Univariate
      analysis was used to determine which of the following variables were related to
      survival: size of the primary tumor and MLNs; RRs of both lesions; degree of
      lymph node (LN) metastasis; clinical stage; and surgical resection. Multivariate
      analysis was then performed to assess the prognostic relevance of each variable.
      The primary tumor was larger than the MLNs in 69% of patients before CRT and in
      40% of patients after CRT. In 79% of the patients, the RR of the primary tumor
      was greater than the RR of the MLNs. The results of the univariate analyses
      showed that a high RR of the MLNs and surgical resection after CRT were
      associated with significantly improved survival. The multivariate analysis
      demonstrated that the RR of MLNs had the strongest influence on survival. The RR
      of LN metastasis should be evaluated as an important prognostic predictor in
      patients with marked LN metastasis of esophageal cancer treated with CRT.

PMID- 17439592
TI  - Non-traumatic vertebral fractures in patients with locally advanced esophageal
      cancer: a previously unreported, unrecognized problem.
AB  - Recent studies suggest cancer therapy may compromise bone integrity. What is the
      rate of vertebral fractures among patients who have received trimodality therapy
      (radiation, chemotherapy, and surgery) for locally advanced esophageal cancer?
      This single-institution, retrospective study attempted to answer this question,
      focusing on 337 patients who had received trimodality therapy for locally
      advanced esophageal cancer between 1996 and 2005. Reports of serial radiographs
      were reviewed to identify vertebral fractures. Duration of follow-up was gathered
      for all esophageal cancer patients with the intention of calculating fracture
      incidence rates. Fracture-related symptoms, types of intervention and fracture
      recurrence were also gleaned from the clinical records. First-time fractures were
      identified in 47 patients, and 45 of these were new since the cancer diagnosis.
      Thus, the first-time fracture incidence rate from the time of cancer diagnosis
      was 12 fractures per 100 patient years. The median time from cancer diagnosis to
      fracture was 9 months. Fifteen (33%) patients were symptomatic. Acknowledging
      that a retrospective study can inadvertently result in information omission, we
      report that pain medications were started in only seven patients (16%), and
      osteoporosis medication in only six (13%). Two patients were hospitalized, and
      two underwent vertebroplasty. The median survival after fracture diagnosis was 36
      months. This report describes a seemingly high fracture incidence rate that
      requires confirmation. If confirmed, future studies should focus on identifying
      risk factors and optimal strategies for the prevention and treatment of vertebral
      fractures in patients with esophageal cancer.

PMID- 17439593
TI  - Tumor-associated macrophages and CD3-zeta expression of tumor-infiltrating
      lymphocytes in human esophageal squamous-cell carcinoma.
AB  - The clinical significance of tumor-associated macrophages (TAMs) and CD3-zeta
      chain expression of tumor-infiltrating lymphocytes (TILs), and their correlation
      in human esophageal squamous cell carcinoma (SCC) are not very clear. Serial
      histological slides from 137 esophageal SCC patients who had undergone tumor
      resection were immunohistochemically studied with anti-CD68, anti-CD3-zeta and
      anti-CD3-epsilon antibodies. TAMs infiltration (expressed as macrophage index,
      M(phi)I) and CD3-zeta expression (judged by Z/E = CD3-zeta+ cells/CD3-epsilon+
      cells ratio) in different tissue compartments were observed. We found that the
      total tumor tissue region had significantly higher macrophage density and lower
      CD3-zeta expression (mean +/- SD: M(phi)I(normal): 225.3 +/- 85.9; Z/E(total):
      0.52 +/- 0.25; n = 137) relative to adjacent histologically normal esophageal
      squamous epithelium (M(phi)I(normal): 60.5 +/- 31.7, P < 0.001; Z/E(normal): 0.79
      +/- 0.35, P = 0.001; n = 70). Significantly higher M(phi)I(stroma) (P = 0.006)
      and lower Z/E(total) (P = 0.016) were detected in patients with lymph node
      metastasis than in those without. Patients with high M(phi)I(total) and
      M(phi)I(cancer) but low Z/E(total) had poorer surgical outcomes. Univariate
      analysis of M(phi)I(total) and multivariate analysis of M(phi)I(total) with
      specific clinico-pathological parameters demonstrated M(phi)I(total) to be an
      independent prognostic factor for survival in esophageal SCC patients (Cox
      proportional hazard model, P = 0.029 and P = 0.031, respectively).

PMID- 17439594
TI  - Serum p53 antibody as a predictor of early recurrence in patients with
      postoperative esophageal squamous cell carcinoma.
AB  - It is reported that surveillance of serum p53 antibody (Ab) is a useful marker in
      detecting esophageal squamous cell carcinoma (ESCC). But there is little reported
      about prognostic significance of serum p53-Ab in postoperative patients with
      ESCC. The aim of this study is to evaluate the significance of preoperative serum
      p53-Ab as a marker of early recurrence after curative resection for ESCC. Enzyme
      linked immunosorvent assay (ELISA) was used to analyze serum p53-Ab before
      treatment in 44 patients with ESCC. Carcinoembryonic antigen (CEA) and squamous
      cell carcinoma antigen (SCC-Ag) were examined by immunoradiometric assay. The
      patients who were strongly positive and positive in serum p53-Ab were more likely
      to have early recurrence after curative resection than seronegative patients.
      There were no significant correlations between CEA, SCC-Ag positivity and early
      recurrence. We found that serum p53-Ab was useful to predict a risk of early
      recurrence after curative surgical resection for ESCC.

PMID- 17439595
TI  - Induction of prostaglandin E synthase by gastroesophageal reflux contents in
      normal esophageal epithelial cells and esophageal cancer cells.
AB  - The synthesis of prostaglandin E2 (PGE2) requires cyclooxygenase (COX) and
      prostaglandin E synthase (PGES). There are two forms of PGES: cytosolic PGES
      (cPGES) and microsomal PGES (mPGES)-1. In this study, we investigated the effects
      of gastroesophageal reflux (GER) contents on PGES and COX-2 in esophageal cells.
      We incubated a human normal esophageal cell line, two esophageal squamous cell
      carcinoma (SCC) cell lines, and two esophageal adenocarcinoma (ADC) cell lines
      with GER contents. The production of PGE2 by these cells was assayed with an
      enzyme immunoassay kit. The protein expression of COX-2, cPGES, and mPGES-1 was
      confirmed by immunoblot analysis. The following results were obtained: GER
      contents induced the expression of COX-2 in all five cell lines. In normal
      esophageal cells, cPGES, but not mPGES-1, was detected in the cytosolic fraction.
      GER contents induced the expression of cPGES in the microsomal fraction. In SCC
      cells, cPGES was expressed in the cytosolic fraction, and mPGES-1 was expressed
      in the microsomal fraction. GER contents induced the expression of mPGES-1 in the
      microsomal fraction. In ADC cells, cPGES was expressed in both the cytosolic and
      microsomal fractions. GER contents induced the expression of both cPGES and mPGES
      1 in the microsomal fraction. In conclusion, our results suggest that GER
      contents induce PGE2 production in esophageal cells. However, there are different
      isoforms of PGES in normal cells, SCC cells, and ADC cells.

PMID- 17439596
TI  - The development of the GERD-HRQL symptom severity instrument.
AB  - The Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL)
      instrument was introduced approximately 10 years ago to provide a quantitative
      method of measuring symptom severity in gastroesophageal reflux disease (GERD).
      Since that time the instrument has been used to assess treatment response to
      medication, endoscopic procedures, and surgery for GERD. However, the development
      of the instrument has progressed over the course of several years, and there is
      no one source which reviews this progress. The purpose of this article is to
      summarize the development and testing of the GERD-HRQL. The GERD-HRQL was
      initially developed to measure the typical symptoms of GERD. It was initially
      determined to have face validity and subsequent studies assessed its content
      validity, criterion validity, concurrent validity, predictive validity and
      construct validity. Reliability was determined by the test-retest method.
      Responsiveness was determined by the effects of treatment. This instrument is
      practical, with little administrative burden. There are few missing responses.
      Because there are 51 possible scores, the instrument has a high level of
      precision; and because of the response anchors, cannot have a floor effect, and
      only 4/372 patients reached the highest score of 50, implying little ceiling
      effect. The instrument has been translated into several languages, and appears
      valid, reliable and practical in each.

PMID- 17439597
TI  - The acute management and surgical reconstruction following failed esophagectomy
      in malignant disease of the esophagus.
AB  - The stomach is the favored organ for reconstruction following esophageal
      resection for malignant disease, but has a 2% failure rate relating to ischemia.
      This event is associated with a high mortality, although appropriate surgical
      management with removal of the conduit can be life-saving. Further reconstruction
      is very challenging. We discuss the management options and surgical techniques
      for these patients. We reviewed of the surgical management of seven patients
      referred to a tertiary center over a 2-year period with failure of their primary
      esophageal reconstruction. Four patients had reconstruction with jejunum (2 free
      transfers and 2 'supercharged' pedicles with microanastomosis in the neck), and
      three with left colon. The route of reconstruction was substernal in four
      patients, subcutaneous in two, and through the left pleural cavity in one. There
      was 0% mortality, and 57% morbidity. The median intensive care unit stay was 2
      days (mean 8, range 1-42). All patients tolerated full enteral nutrition, and had
      a satisfactory functional outcome. Failure of the conduit post-esophagectomy is a
      rare but serious complication, and these patients require complex surgical
      reconstruction. The surgical techniques described require a specialist
      multidisciplinary approach, but good clinical and functional outcomes are
      possible, even in patients with an underlying malignancy.

PMID- 17439598
TI  - Characterization of tissue autofluorescence in Barrett's esophagus by confocal
      fluorescence microscopy.
AB  - High grade dysplasia and early cancer in Barrett's esophagus can be distinguished
      in vivo by endoscopic autofluorescence point spectroscopy and imaging from non
      dysplastic Barrett's mucosa. We used confocal fluorescence microscopy for ex vivo
      comparison of autofluorescence in non-dysplastic and dysplastic Barrett's
      esophagus. Unstained frozen sections were obtained from snap-frozen Barrett's
      esophagus biopsy samples and scanned with confocal fluorescence microscopy (458
      nm excitation; 505-550 nm [green] and > 560 nm [red] emission). Digital
      micrographs were taken from areas with homogenous and specific histopathology.
      Visual inspection and statistical analysis were used to evaluate the image
      datasets. Dysplastic and non-dysplastic Barrett's esophagus epithelia fluoresced
      mainly in the green spectrum and the main sources of autofluorescence were the
      cytoplasm and lamina propria. High-grade dysplasia was differentiated from non
      dysplastic Barrett's esophagus by microstructural tissue changes. However, there
      were no specific changes in either the locations or average intensities of
      intrinsic green and red autofluorescence at the epithelial level that could
      differentiate between dysplastic and non-dysplastic Barrett's esophagus
      epithelia, ex vivo. Detectable differences in autofluorescence between BE and
      dysplasia/cancer in vivo are probably not caused by specific changes in
      epithelial fluorophores but are likely due to other inherent changes (e.g.
      mucosal thickening and increased microvascularity) attenuating autofluorescence
      from the collagen-rich submucosa. Furthermore, confocal fluorescence microscopy
      provides 'histology-like' imaging of Barrett's tissues and may offer a unique
      opportunity to exploit microstructural tissue changes occurring during neoplastic
      transformation for in vivo detection of high-grade dysplasia in Barrett's
      patients using newly developed confocal fluorescence microendoscopy devices.

PMID- 17439599
TI  - Correlation between esophageal contraction amplitude and lower esophageal
      sphincter pressure in patients with nutcracker esophagus.
AB  - Nutcracker esophagus (NE) is a primary esophageal motility disorder characterized
      by high-wave amplitude at the distal esophagus. The aim of this study was to
      analyze patients with NE and determine the relationship between distal esophageal
      contraction amplitude and lower esophageal sphincter (LES) pressure. Esophageal
      manometry tracings of patients with NE, defined as the presence of distal
      contraction amplitude of more than 182 mmHg after wet swallow, were analyzed. LES
      pressure was measured as the mean end-expiratory value. Spearman's correlation
      coefficient analysis was used to compare esophageal contraction amplitude with
      LES pressure. This comparison was also performed in patients with isolated
      hypertensive LES (HLES) and in subjects with normal manometry. Forty patients (25
      female, 15 male; mean age 54 years) with NE were included in the study. Mean (SD)
      distal esophageal contraction amplitude was 230 (35.7) mmHg and mean LES pressure
      was 27.3 (5.7) mmHg. Esophageal contraction amplitude showed a positive
      correlation with LES pressure (r = 0.49, P < 0.01). In contrast, no correlation
      was found in patients with HLES (r = 0.21, P > 0.05) and in those with a normal
      manometric study (r = 0.18, P > 0.05). It is concluded that in patients with
      nutcracker esophagus a positive correlation exists between distal esophageal
      contraction amplitude and LES pressure, suggesting a diffuse hypertensive pattern
      involving smooth muscle at the distal esophagus and adjacent LES.

PMID- 17439600
TI  - Comparison of the effect of a cornstarch thickened formula and strengthened
      regular formula on regurgitation, gastric emptying and weight gain in infantile
      regurgitation.
AB  - The purpose of this study was to evaluate the efficacy of a specially selected
      cornstarch-supplemented formula on clinical symptoms, gastric emptying and weight
      gain in infants with regurgitation. We performed a prospective randomised trial
      evaluating the therapeutic efficacy of two different formula feedings (cornstarch
      thickened formula, group A; 25% strengthened formula, group B) in 81 young
      infants with regurgitation/vomiting > or = 3 times/day. A Tc-99 m milk
      scintigraphy was performed at inclusion and after 2 months to quantify gastric
      emptying time; all studied infants underwent a 2-month period of clinical follow
      up evaluating regurgitation and body weight gain. At inclusion, group A and B had
      a similar age and weight. After the 2-month period of intervention, regurgitation
      and vomiting had both greater decrease (both P < 0.001 at 1 and 2 months) in
      group A (from a score of 4.19 +/- 1.71 to 0.93 +/- 0.42) than in group B (from a
      score of 4.15 +/- 1.68 to 2.89 +/- 1.16). Non-regurgitation symptoms
      (irritability, cough, choking, night-waking) decreased (P = 0.045 at 1 month and
      0.017 at 2 months) in group A (from a score of 18 at baseline to 3 after 8 weeks)
      as compared to group B (from a score of 18 at baseline to 11 after 8 weeks).
      Weight increased more in group A (29.1 +/- 3.9 g/day over 8 weeks) versus group B
      (23.6 +/- 3.5 g/day over 8 weeks) (P < 0.01 at 1 and 2 months) Gastric emptying
      improved significantly in group A as compared with group B (all P < 0.001 for
      T1/2, and residual volume at 60 and 90 min). Ingested feeding volume was
      significantly larger in the group receiving cornstarch-thickened formula, both at
      4 weeks (109.4 +/- 24.5 vs. 98.5 +/- 23.6 mL/meal) (P: 0.042) and at 8 weeks
      (137.6 +/- 27.9 vs. 115.7 +/- 26.5 mL/meal) (P < 0.001). Cornstarch-thickened
      formula feeding decreases the frequency of regurgitation/vomiting, provides
      better body weight gain and has an accelerated gastric emptying in comparison to
      a 25% strengthened regular formula in infants with regurgitation.

PMID- 17439601
TI  - Levels of evidence available for techniques in antireflux surgery.
AB  - The objective of this study was to determine the levels of evidence and grades of
      recommendations available for techniques in antireflux surgery. Areas of
      technical controversy in antireflux surgery were identified and developed into
      eight answerable questions. The external evidence was surveyed using the
      databases Medline and EMBASE. Abstracts and appropriate articles were identified
      from January 1966 to December 2005. A set of search strategies was systematically
      employed to determine the levels of evidence available for each clinical
      question. Primary outcome measures included the determination of levels of
      evidence and grade of recommendation based on The Oxford Center for Evidence
      Based Medicine. Secondary outcome measures included for randomized controlled
      trials were Jadad scores, noting the presence of a sample size calculation, and
      the determination of an effect estimate and the reporting of a confidence
      interval. Higher quality randomized controlled trials (mostly level 2b,
      occasional level 1b) existed to answer three questions: whether to complete a 360
      degrees or partial wrap; whether or not to divide the short gastric vessels; and
      whether to perform laparoscopic or open surgery. Lower quality randomized
      controlled trials were available to determine whether the use of mesh was
      helpful, whether or not to use a bougie catheter for calibration of the wrap, and
      whether an anterior or posterior wrap results in a superior outcome. This was
      deemed to be of inferior grade of recommendation due to the lack (< 2) of trials
      available and the sole presence of level 2b evidence. The final two questions:
      whether to complete fundoplication using a thoracic or abdominal approach and
      whether to use intraoperative manometry relied exclusively upon level 4 evidence
      and thus received a lower grade of recommendation. A higher Jadad score seemed to
      be associated with studies having a higher level of evidence available to answer
      the question. Sample size calculations were given to answer three questions.
      Effect estimate was difficult to interpret given inconsistent findings, composite
      outcomes and lack of reported confidence intervals. In conclusion, antireflux
      surgery has many randomized controlled trials available upon which to base
      clinical practice. Unfortunately, these are generally of poor quality. We
      recommend that esophageal surgeons determine consistent outcome measures and
      endeavor to improve the quality of randomized controlled trials they perform.

PMID- 17439602
TI  - Pseudoachalasia: not only esophago-gastric cancer.
AB  - Pseudoachalasia is a rare clinical entity which has clinical, radiographic and
      manometric features often indistinguishable from achalasia. A small primary
      adenocarcinoma arising at the gastroesophageal junction or a tumor of the distal
      esophagus are the most frequent causes. Rarely, processes other than
      esophagogastric cancers may lead to the development of pseudoachalasia. We
      present three cases of pseudoachalasia in which the primary cause of the disease
      was not an esophagogastric cancer. The causes were a pancreatic carcinoma, a
      breast cancer and an histiocytosis X. Aspects of these three patients' diagnostic
      and therapeutic course are discussed in detail.

PMID- 17439603
TI  - Successful treatment of S-1 + CDDP followed by salvage EMR for a case with
      metastatic Barrett's esophageal cancer.
AB  - A 62-year-old woman with Barrett's esophageal cancer was hospitalized. Abdominal
      CT confirmed metastases to the liver and lymph nodes, for which surgical excision
      and radiotherapy were not indicated. We started chemotherapy with a course of
      daily oral S-1 at a dose of 80 mg/m(2) for 21 days, with a 2-hour drip of
      cisplatin at 60 mg/m(2) on day 8. Breaks of 14 drug-free days were given between
      courses. After two courses, a repeat CT confirmed that the liver and lymph node
      metastases had disappeared; after three courses, another CT confirmed that the
      metastatic foci were still absent, so we judged the disease to be in complete
      remission. Endoscopy and upper GI series confirmed that the primary tumor was
      reduced, and endoscopic mucosal resection performed using the strip biopsy
      method. The excision specimen was well differentiated adenocarcinoma, and mucosal
      invasion, and the excision stump was negative. After two more courses of S-1 +
      cisplatin, chemotherapy has been suspended with the patient's consent, and in the
      21 months after endoscopic mucosal resection, no recurrence has been observed.
      This is a rare case of metastatic Barrett's esophageal cancer in which the
      metastases were eradicated by S-1 + cisplatin, and the primary tumor successfully
      excised by endoscopic mucosal resection after downstaging.

PMID- 17439604
TI  - Esophagectomy for complications of esophageal intramural pseudodiverticulosis.
AB  - This report describes the clinical course of a patient with complications of
      esophageal intramural pseudodiverticulosis. The condition led to fistulization
      and abscess formation in the mediastinum. The initial presentation was for the
      septic process and appropriate antibiotic therapy led to infection control while
      the abscess drained spontaneously back into the esophageal lumen. A long
      stricture affecting the distal half of the esophagus became evident after a few
      months and could not be managed by repeat dilatations. After appropriate
      preparation, subtotal esophagectomy was offered to the patient with an initial
      right thoracic approach followed by laparotomy and left cervical reconstruction.
      A total gastric tube was used for reconstruction and placed in a substernal
      position. An uneventful postoperative evolution led to normal swallowing comfort.

PMID- 17439605
TI  - Down syndrome and esophageal cancer.
AB  - We present two cases of Down syndrome with inoperable esophageal cancer at a
      relatively young age. The first patient had a locally advanced squamous cell
      carcinoma of the distal esophagus. The second had a short circular adenocarcinoma
      of the distal esophagus with peritoneal and liver metastases. The cases are
      discussed with regard to the current literature on Down syndrome and esophageal
      cancer.

PMID- 17439606
TI  - Multinodular leiomyoma of the esophagus with internodular hydropic degeneration
      and bulbous serosal protrusions similar to cotyledonoid uterine leiomyoma.
AB  - Leiomyoma is the most common benign tumor of the esophagus, and usually occurs as
      a solitary mass. We report a case of esophageal leiomyoma which shows
      multinodular growth pattern with bulbous serosal protrusions. The patient was a
      26-year-old woman who had an esophageal ulcerated mass near the gastroesophageal
      junction. Clinical findings were consistent with carcinoma of the gastric cardia.
      Based on the clinical diagnosis, total gastrectomy with distal esophagectomy was
      performed. Histologic appearance of the resected specimen was consistent with
      leiomyoma which had a multinodular growth pattern.

PMID- 17439607
TI  - Introducing desirable transgenes into insect populations using Y-linked meiotic
      drive - a theoretical assessment.
AB  - The use of genetic drive mechanisms to replace native mosquito genotypes with
      individuals bearing antipathogen transgenes is a potential strategy for
      repressing insect transmission of human diseases such as malaria and dengue.
      Antipathogen transgenes have been developed and tested, but efficient gene drive
      mechanisms are lacking. Here we theoretically assess the feasibility of
      introducing antipathogen genes into wild Aedes aegypti populations by using a
      naturally occurring meiotic drive system. We consider the release of males having
      both a Y-linked meiotic drive gene and an X-linked drive-insensitive response
      allele to which an antipathogen gene is linked. We use mathematical models and
      computer simulations to determine how the post-introduction dynamics of the
      antipathogen gene are affected by specific genetic characteristics of the system.
      The results show that when the natural population is uniformly sensitive to the
      meiotic drive gene, the antipathogen gene may be driven close to fixation if the
      fitness costs of the drive gene, the insensitive response allele, and the
      antipathogen gene are low. However, when the natural population has a small
      proportion of an X-linked insensitive response allele or an autosomal gene that
      strongly reduces the effect of the drive gene, the antipathogen gene does not
      spread if it has an associated fitness cost. Our modeling results provide a
      theoretical foundation for further experimental tests.

PMID- 17439608
TI  - The mutation matrix and the evolution of evolvability.
AB  - Evolvability is a key characteristic of any evolving system, and the concept of
      evolvability serves as a unifying theme in a wide range of disciplines related to
      evolutionary theory. The field of quantitative genetics provides a framework for
      the exploration of evolvability with the promise to produce insights of global
      importance. With respect to the quantitative genetics of biological systems, the
      parameters most relevant to evolvability are the G-matrix, which describes the
      standing additive genetic variances and covariances for a suite of traits, and
      the M-matrix, which describes the effects of new mutations on genetic variances
      and covariances. A population's immediate response to selection is governed by
      the G-matrix. However, evolvability is also concerned with the ability of
      mutational processes to produce adaptive variants, and consequently the M-matrix
      is a crucial quantitative genetic parameter. Here, we explore the evolution of
      evolvability by using analytical theory and simulation-based models to examine
      the evolution of the mutational correlation, r(mu), the key parameter determining
      the nature of genetic constraints imposed by M. The model uses a diploid,
      sexually reproducing population of finite size experiencing stabilizing selection
      on a two-trait phenotype. We assume that the mutational correlation is a third
      quantitative trait determined by multiple additive loci. An individual's value of
      the mutational correlation trait determines the correlation between pleiotropic
      effects of new alleles when they arise in that individual. Our results show that
      the mutational correlation, despite the fact that it is not involved directly in
      the specification of an individual's fitness, does evolve in response to
      selection on the bivariate phenotype. The mutational variance exhibits a weak
      tendency to evolve to produce alignment of the M-matrix with the adaptive
      landscape, but is prone to erratic fluctuations as a consequence of genetic
      drift. The interpretation of this result is that the evolvability of the
      population is capable of a response to selection, and whether this response
      results in an increase or decrease in evolvability depends on the way in which
      the bivariate phenotypic optimum is expected to move. Interestingly, both
      analytical and simulation results show that the mutational correlation
      experiences disruptive selection, with local fitness maxima at -1 and +1. Genetic
      drift counteracts the tendency for the mutational correlation to persist at these
      extreme values, however. Our results also show that an evolving M-matrix tends to
      increase stability of the G-matrix under most circumstances. Previous studies of
      G-matrix stability, which assume nonevolving M-matrices, consequently may
      overestimate the level of instability of G relative to what might be expected in
      natural systems. Overall, our results indicate that evolvability can evolve in
      natural systems in a way that tends to result in alignment of the G-matrix, the M
      matrix, and the adaptive landscape, and that such evolution tends to stabilize
      the G-matrix over evolutionary time.

PMID- 17439609
TI  - Genetic analysis of autosomal and X-linked markers across a mouse hybrid zone.
AB  - In this paper, we present results of the first comprehensive study of the
      introgression of both autosomal and sex-chromosome markers across the central
      European portion of the hybrid zone between two house mouse subspecies, Mus
      musculus musculus and M. m. domesticus. More than 1800 individuals sampled from
      105 sites were analyzed with a set of allozyme loci (hopefully representing
      neutral or nearly neutral markers) and X-linked loci (which are assumed to be
      under selection). The zone center is best modeled as a single straight line
      independent of fine-scale local geographic or climatic conditions, being
      maintained by a balance between dispersal and selection against hybrids. The
      width (w) of the multilocus autosomal cline was estimated as 9.6 km whereas the
      estimate for the compound X-chromosome cline was about 4.6 km only. As the former
      estimate is comparable to that of the Danish portion of the zone (assumed to be
      much younger than the central European one), zone width does not appear to be
      related to its age. The strength (B) of the central barrier was estimated as
      about 20 km; with dispersal (sigma) of about 1 km/gen(1/2), this means effective
      selection (s*) is approximately 0.06-0.09 for autosomal loci and about 0.25 for X
      linked loci. The number of loci under selection was estimated as N= 56-99 for
      autosomes and about 380 for X-linked loci. Finally, we highlight some potential
      pitfalls in hybrid zone analyses and in comparisons of different transects. We
      suggest that conclusions about parts of the mouse genome involved in reproductive
      isolation and speciation should be drawn with caution and that analytical
      approaches always providing some estimates should not be used without due care
      regarding the support or confidence of such estimates, especially if conclusions
      are based on the difference between these estimates. Finally, we recommend that
      analysis in two-dimensional space, dense sampling, and rigorous treatment of
      data, including inspection of likelihood profiles, are essential for hybrid zone
      studies.

PMID- 17439610
TI  - Adaptive gamete-recognition divergence in a hybridizing Mytilus population.
AB  - Gamete-recognition proteins often evolve rapidly, but it is not known if their
      divergence occurs within species and corresponds with the evolution of
      reproductive isolation, or if divergence typically accumulates between already
      isolated lineages. We examined the evolution of a candidate gamete-recognition
      protein in several sympatric and allopatric populations of Mytilus blue mussels,
      species that hybridize in nature. Within a single species, Mytilus
      galloprovincialis, we found adaptive divergence of Lysin-M7, a sperm acrosomal
      protein that dissolves the egg vitelline envelope during fertilization. Mytilus
      galloprovincialis Lysin-M7 alleles group into two distinct clades (termed G and
      G(D)), and individual alleles in these clades are separated from each other by at
      least three and up to eleven amino-acid substitutions. Maximum-likelihood
      estimates of selective pressure (dN/dS =omega) implicate selection in the
      divergence between M. galloprovincialis Lysin-M7 clades, and within the G(D)
      clade. Exact tests of population differentiation indicate that the relative
      frequency of G and G(D) Lysin-M7 alleles differs significantly among M.
      galloprovincialis populations. Compared with allopatric Mediterranean samples,
      Lysin-M7 alleles in the G(D) clade are found at elevated frequency in samples
      from the East Atlantic and California, areas of secondary contact and
      hybridization between Mytilus species, and Australia, an area of unknown species
      composition. Adaptive divergence between the alleles most common in allopatry and
      those found at elevated frequency in samples from sympatry suggests that
      selection pressures acting in hybridizing populations, likely following
      Pleistocene secondary contact with M. edulis in the East Atlantic, drove the
      divergence of Lysin-M7 in M. galloprovincialis.

PMID- 17439611
TI  - Adaptive radiation of gall-inducing insects within a single host-plant species.
AB  - Speciation of plant-feeding insects is typically associated with host-plant
      shifts, with subsequent divergent selection and adaptation to the ecological
      conditions associated with the new plant. However, a few insect groups have
      apparently undergone speciation while remaining on the same host-plant species,
      and such radiations may provide novel insights into the causes of adaptive
      radiation. We used mitochondrial and nuclear DNA to infer a phylogeny for 14
      species of gall-inducing Asphondylia flies (Diptera: Cecidomyiidae) found on
      Larrea tridentata (creosote bush), which have been considered to be monophyletic
      based on morphological evidence. Our phylogenetic analyses provide strong support
      for extensive within-host plant speciation in this group, and it demonstrates
      that diversification has involved numerous shifts between different plant organs
      (leaves, buds, flowers, and stems) of the same host-plant species. Within-plant
      speciation of Asphondylia is thus apparently facilitated by the opportunity to
      partition the plant ecologically. One clade exhibits temporal isolation among
      species, which may have facilitated divergence via allochronic shifts. Using a
      novel method based on Bayesian reconstruction, we show that the rate of change in
      an ecomorphological trait, ovipositor length, was significantly higher along
      branches with inferred shifts between host-plant organs than along branches
      without such shifts. This finding suggests that Larrea gall midges exhibit close
      morphological adaptation to specific host-plant parts, which may mediate
      ecological transitions via disruptive selection.

PMID- 17439612
TI  - Parasite-driven genetic change in a natural population of Daphnia.
AB  - A substantial body of theory indicates that parasites may mould the population
      genetic structure of their hosts, but few empirical studies have directly linked
      parasitism to genetic dynamics. We used molecular markers (allozymes) to
      investigate genotype frequency changes in a natural population of the crustacean
      Daphnia magna in relation to an epidemic of the bacterial pathogen Pasteuria
      ramosa. The population experienced a severe epidemic during the study period in
      which parasite prevalence reached 100% of the adult portion of the population.
      The parasite epidemic was associated with genetic change in the host population.
      Clonal diversity was observed to decrease as parasite prevalence increased in the
      population, and tests for differences in the clonal composition of the population
      before, during, and after the epidemic indicated that significant change had
      occurred. A laboratory infection experiment showed that the genotypes which were
      more common following the peak of the parasite epidemic were also the most
      resistant to parasite infection. Thus, this study provides an illustration of
      parasite-mediated selection in the wild.

PMID- 17439613
TI  - The genetic architecture of immune defense and reproduction in male Bombus
      terrestris bumblebees.
AB  - Understanding the architecture of genetic variation, that is the number, effect,
      location, and interaction, of genes responsible for phenotypic variability in
      nature is important for the understanding of microevolutionary processes. In this
      study, we have used a quantitative trait loci (QTL) approach to uncover the
      genetic architecture of fitness-relevant traits associated with reproduction and
      immune defense in male Bombus terrestris bumblebees. Three male reproductive
      investment traits, the number and length of the produced sperm and the size of
      the accessory glands, were studied. Two branches of the insect innate immune
      system, the activation of the Phenoloxidase-cascade and the hemolymph's
      antibacterial activity, were investigated. We found that variation in most of the
      studied traits is based on a network of minor QTLs and epistatic interactions.
      Unexpectedly, there was no evidence for phenotypic or genetic trade-offs between
      the presumably costly investment in immune defense and reproductive effort in
      this population for the measured traits. In fact, we found a positive
      correlation, both, in phenotype and genetic architecture for the number of
      produced sperm and antibacterial activity against an insect pathogen. A major
      finding for all traits analyzed was that the epistatic interactions accounted for
      a major proportion of the explained phenotypic variance. Especially for traits
      involved in immune defense, this pattern highlights the possible role of
      parasites in the evolution and maintenance of recombination and sexual
      reproduction.

PMID- 17439614
TI  - Shorter sperm confer higher competitive fertilization success.
AB  - Spermatozoa exhibit taxonomically widespread patterns of divergent morphological
      evolution. However, the adaptive significance of variation in sperm morphology
      remains unclear. In this study we examine the role of natural variation in sperm
      length on fertilization success in the dung beetle Onthophagus taurus. We
      conducted sperm competition trials between males that differed in the length of
      their sperm and determined the paternity of resulting offspring using amplified
      fragment length polymorphism (AFLP) markers. We also quantified variation in the
      size and shape of the female's sperm storage organ to determine whether female
      morphology influenced the competitiveness of different sperm morphologies. We
      found that fertilization success was biased toward males with relatively shorter
      sperm, but that selection on sperm length was dependent on female tract
      morphology; selection was directional for reduced sperm length across most of the
      spermathecal size range, but stabilizing in females with the smallest
      spermathecae. Our data provide empirical support for the theory that sperm
      competition should favor the evolution of numerous tiny sperm. Moreover, because
      sperm length is both heritable and genetically correlated with condition, our
      results are consistent with a process by which females can accrue genetic
      benefits for their offspring from the incitement of sperm competition and/or
      cryptic female choice, as proposed by the "sexy sperm" and "good sperm" models
      for the evolution of polyandry.

PMID- 17439615
TI  - The form of sexual selection on male genitalia cannot be inferred from within
      population variance and allometry - a case study in Aquarius remigis.
AB  - Male genital morphology in insects and arachnids is characterized by static
      hypoallometry and low intrapopulational levels of phenotypic variation relative
      to other male traits. The one-size-fits-all model of genital evolution attributes
      these patterns to stabilizing sexual selection. This model relies on the
      assumption that the observed patterns of variation and allometry reflect the form
      of sexual selection acting these traits. We test this by examining the patterns
      of scaling and trait variation for a set of genitalic and somatic morphological
      traits in male water striders (Aquarius remigis). This suite of traits is of
      particular interest because previous work has shown that the genitalic traits are
      under strong directional selection whereas the somatic traits are under either
      weak directional or stabilizing selection. Because the selection regime for these
      traits is known, we can, for the first time, test the purported relationship
      between trait variation, scaling, and the form of sexual selection. We show that
      the patterns of variation and scaling of these traits differ sharply from those
      predicted for traits experiencing strong directional sexual selection.
      Specifically, the male genital structures show static hypoallometry and low
      intrapopulational levels of phenotypic variation relative to other male traits,
      in spite of consistent, strong, directional sexual selection. These scaling
      relationships and levels of variation are typical of genital traits in other
      insect species, where they have been presumed to reflect stabilizing sexual
      selection. Our data clearly refute the assumption of the one-size-fits-all
      hypothesis that hypoallometric scaling of genitalic traits implies stabilizing
      selection. We discuss the implications of this finding and propose future
      directions for improving our current understanding of genital evolution in
      arthropods.

PMID- 17439616
TI  - Sexual selection and allometry: a critical reappraisal of the evidence and ideas.
AB  - One of the most pervasive ideas in the sexual selection literature is the belief
      that sexually selected traits almost universally exhibit positive static
      allometries (i.e., within a sample of conspecific adults, larger individuals have
      disproportionally larger traits). In this review, I show that this idea is
      contradicted by empirical evidence and theory. Although positive allometry is a
      typical attribute of some sexual traits in certain groups, the preponderance of
      positively allometric sexual traits in the empirical literature apparently
      results from a sampling bias reflecting a fascination with unusually exaggerated
      (bizarre) traits. I review empirical examples from a broad range of taxa
      illustrating the diversity of allometric patterns exhibited by signal, weapon,
      clasping and genital traits, as well as nonsexual traits. This evidence suggests
      that positive allometry may be the exception rather than the rule in sexual
      traits, that directional sexual selection does not necessarily lead to the
      evolution of positive allometry and, conversely, that positive allometry is not
      necessarily a consequence of sexual selection, and that many sexual traits
      exhibit sex differences in allometric intercept rather than slope. Such diversity
      in the allometries of secondary sexual traits is to be expected, given that
      optimal allometry should reflect resource allocation trade-offs, and patterns of
      sexual and viability selection on both trait size and body size. An unbiased
      empirical assessment of the relation between sexual selection and allometry is an
      essential step towards an understanding of this diversity.

PMID- 17439617
TI  - Song and plumage evolution in the New World orioles (Icterus) show similar
      lability and convergence in patterns.
AB  - Both song and color patterns in birds are thought to evolve rapidly and exhibit
      high levels of homoplasy, yet few previous studies have compared the evolution of
      these traits systematically using the same taxa. Here we reconstruct the
      evolution of song in the New World orioles (Icterus) and compare patterns of
      vocal evolution to previously reconstructed patterns of change in plumage
      evolution in this clade. Individual vocal characters exhibit high levels of
      homoplasy, reflected in a low overall consistency index (CI = 0.27) and retention
      index (RI = 0.35). Levels of lability in song are comparable to those found for
      oriole plumage patterns using the same taxa (CI = 0.31, RI = 0.63), but are
      strikingly dissimilar to the conservative patterns of change seen in the songs of
      oropendolas (Psarocolius, Ocyalus; CI = 0.82, RI = 0.87), a group closely related
      to the orioles. Oriole song is also similar to oriole plumage in exhibiting
      repeated convergence in overall patterns, with some distantly related taxa
      sounding remarkably similar. Thus, both song and plumage in orioles show repeated
      convergence in individual elements and in overall patterns across the clade,
      suggesting that both of these character classes are highly labile between taxa
      yet highly conserved within the genus. Our results provide new insights into the
      tempo and mode of evolution in sexually selected traits within and across clades.

PMID- 17439618
TI  - The phylogeny of the Pentaschistis clade (Danthonioideae, Poaceae) based on
      chloroplast DNA, and the evolution and loss of complex characters.
AB  - We construct a species-level phylogeny for the Pentaschistis clade based on
      chloroplast DNA, from the following regions: trnL-F, trnT-L, atpB-rbcL, rpL16,
      and trnD-psbA. The clade comprises 82 species in three genera, Pentaschistis,
      Pentameris, and Prionanthium. We demonstrate that Prionanthium is nested in
      Pentaschistis and that this clade is sister to a clade of Pentameris plus
      Pentaschistis tysonii. Forty-three of the species in the Pentaschistis clade have
      multicellular glands and we use ancestral character state reconstruction to show
      that they have been gained twice or possibly once, and lost several times. We
      suggest that the maintenance, absence, loss, and gain of glands are correlated
      with leaf anatomy type, and additionally that there is a difference in the degree
      of diversification of lineages that have these different character combinations.
      We propose that both glands and sclerophyllous leaves act as defense systems
      against herbivory, and build a cost/benefit model in which multicellular glands
      or sclerophyllous leaves are lost when the alternative defense system evolves. We
      also investigate the association between leaf anatomy type and soil nutrient type
      on which species grow. There is little phylogenetic constraint in soil nutrient
      type on members of the Pentaschistis clade, with numerous transitions between
      oligotrophic and eutrophic soils. However, only orthophyllous-leaved species
      diversify on eutrophic soils. We suggest that the presence of these glands
      enables the persistence of orthophyllous lineages and therefore diversification
      of the Pentaschistis clade on eutrophic as well as oligotrophic soils.

PMID- 17439619
TI  - Lineages with long durations are old and morphologically average: an analysis
      using multiple datasets.
AB  - Lineage persistence is as central to biology as evolutionary change. Important
      questions regarding persistence include: why do some lineages outlive their
      relatives, neither becoming extinct nor evolving into separate lineages? Do these
      long-duration lineages have distinctive ecological or morphological traits that
      correlate with their geologic durations and potentially aid their survival? In
      this paper, I test the hypothesis that lineages (species and higher taxa) with
      longer geologic durations have morphologies that are more average than expected
      by chance alone. I evaluate this hypothesis for both individual lineages with
      longer durations and groups of lineages with longer durations, using more than 60
      published datasets of animals with adequate fossil records. Analyses presented
      here show that groups of lineages with longer durations fall empirically into one
      of three theoretically possible scenarios, namely: (1) the morphology of groups
      of longer duration lineages is closer to the grand average of their inclusive
      group, that is, their relative morphological distance is smaller than expected by
      chance alone, when compared with rarified samples of their shorter duration
      relatives (a negative group morpho-duration distribution); (2) the relative
      morphological distance of groups of longer duration lineages is no different from
      rarified samples of their shorter duration relatives (a null group morpho
      duration distribution); and (3) the relative morphological distance of groups of
      longer duration lineages is greater than expected when compared with rarified
      samples of their shorter duration relatives (a positive group morpho-duration
      distribution). Datasets exhibiting negative group morpho-duration distributions
      predominate. However, lineages with higher ranks in the Linnean hierarchy
      demonstrate positive morpho-duration distributions more frequently. The relative
      morphological distance of individual longer duration lineages is no different
      from that of rarified samples of their shorter duration relatives (a null
      individual morpho-duration distribution) for the majority of datasets studied.
      Contrary to the common idea that very persistent lineages are special or unique
      in some significant way, both the results from analyses of long-duration lineages
      as groups and individuals show that they are morphologically average. Persistent
      lineages often arise early in a group's history, even though there is no prior
      expectation for this tendency in datasets of extinct groups. The implications of
      these results for diversification histories and niche preemption are discussed.

PMID- 17439620
TI  - The phenotypic and genetic covariance structure of drosphilid wings.
AB  - Evolutionary constraint results from the interaction between the distribution of
      available genetic variation and the position of selective optima. The
      availability of genetic variance in multitrait systems, as described by the
      additive genetic variance-covariance matrix (G), has been the subject of recent
      attempts to assess the prevalence of genetic constraints. However, evolutionary
      constraints have not yet been considered from the perspective of the phenotypes
      available to multivariate selection, and whether genetic variance is present in
      all phenotypes potentially under selection. Determining the rank of the
      phenotypic variance-covariance matrix (P) to characterize the phenotypes
      available to selection, and contrasting it with the rank of G, may provide a
      general approach to determining the prevalence of genetic constraints. In a study
      of a laboratory population of Drosophila bunnanda from northern Australia we
      applied factor-analytic modeling to repeated measures of individual wing
      phenotypes to determine the dimensionality of the phenotypic space described by
      P. The phenotypic space spanned by the 10 wing traits had 10 statistically
      supported dimensions. In contrast, factor-analytic modeling of G estimated for
      the same 10 traits from a paternal half-sibling breeding design suggested G had
      fewer dimensions than traits. Statistical support was found for only five and two
      genetic dimensions, describing a total of 99% and 72% of genetic variance in wing
      morphology in females and males, respectively. The observed mismatch in
      dimensionality between P and G suggests that although selection might act to
      shift the intragenerational population mean toward any trait combination,
      evolution may be restricted to fewer dimensions.

PMID- 17439621
TI  - Discordant divergence times among Z-chromosome regions between two ecologically
      distinct swallowtail butterfly species.
AB  - We investigate multilocus patterns of differentiation between parental
      populations of two swallowtail butterfly species that differ at a number of
      ecologically important sex-linked traits. Using a new coalescent-based approach,
      we show that there is significant heterogeneity in estimated divergence times
      among five Z-linked markers, rejecting a purely allopatric speciation model. We
      infer that the Z chromosome is a mosaic of regions that differ in the extent of
      historical gene flow, potentially due to isolating barriers that prevent the
      introgression of species-specific traits that result in hybrid incompatibilities.
      Surprisingly, a candidate region for a strong barrier to introgression, Ldh, does
      not show a significantly deeper divergence time than other markers on the Z
      chromosome. Our approach can be used to test alternative models of speciation and
      can potentially assign chronological order to the appearance of factors
      contributing to reproductive isolation between species.

PMID- 17439622
TI  - Diversity and trans-arctic invasion history of mitochondrial lineages in the
      North Atlantic Macoma balthica complex (Bivalvia: Tellinidae).
AB  - The history of repeated inter- or transoceanic invasions in bivalve mollusks of
      the circumpolar Macoma balthica complex was assessed from mtDNA COIII sequences.
      The data suggest that four independent trans-Arctic invasions, from the Pacific,
      gave rise to the current lineage diversity in the North Atlantic. Unlike in many
      other prominent North Atlantic littoral taxa, no evidence for (postinvasion)
      trans-Atlantic connections was found in the M. balthica complex. The earliest
      branch of the mtDNA tree is represented by the temperate-boreal North American
      populations (=Macoma petalum), separated from the M. balthica complex proper in
      the Early Pliocene at latest. The ensuing trans-Arctic invasions established the
      North European M. b. rubra, which now prevails on the North Sea and northeast
      Atlantic coasts, about two million years ago, and the currently northwest
      Atlantic M. balthica lineage in the Canadian Maritimes, in the Middle
      Pleistocene. The final reinvasion(s) introduced a lineage that now prevails in a
      number of North European marginal seas and is still hardly distinguishable from
      North Pacific mtDNA (M. b. balthica). We used coalescence simulation analyses to
      assess the age of the latest invasion from the Pacific to the northeast Atlantic.
      The results refute the hypothesis of recent, human-mediated reintroductions
      between northeast Pacific and the North European marginal seas in historical
      times. Yet they also poorly fit the alternative hypotheses of an early
      postglacial trans-Arctic invasion (< 11 thousand years ago), or an invasion
      during the previous Eemian interglacial (120 thousand years ago). Divergence time
      estimates rather fall in the Middle Weichselian before the Last Glacial Maximum,
      in conflict with the conventional thinking of trans-Arctic biogeographical
      connections; an early Holocene reinvasion may still be regarded as the most
      plausible scenario. Today, the most recently invaded Pacific mtDNA lineage is
      found admixed with the earlier established European Atlantic "rubra" lineage in
      the Baltic Sea and in Barents Sea populations east of the Varanger peninsula, and
      it is practically exclusive in the White and Pechora seas. Yet mtDNA does not
      always constitute an unequivocal taxonomic marker at individual level; the
      marginal populations represent hybrid swarms of the Atlantic and Pacific lineages
      in their nuclear genes.

PMID- 17439623
TI  - Biogeographical basis of recent phenotypic divergence among birds: a global study
      of subspecies richness.
AB  - Theory predicts that biogeographic factors should play a central role in
      promoting population divergence and speciation. Previous empirical studies into
      biogeography and diversification have been relatively restricted in terms of the
      geographical area, phylogenetic scope, and the range of biogeographic factors
      considered. Here we present a global analysis of allopatric phenotypic divergence
      (measured as subspecies richness) across more than 9600 bird species. The main
      aim of this study was to examine the extent to which biogeographical factors can
      explain patterns of phenotypic divergence. Analysis of the taxonomic distribution
      of subspecies among species suggests that subspecies formation and extinction
      have occurred at a considerably faster rate than has species formation. However,
      the observed distribution departs from the expectation under a random birth-death
      model of diversification. Across 19 phylogenetic trees, we find no significant
      linear relationship between species age and subspecies richness, implying that
      species age is a poor predictor of subspecies richness. Both subspecies richness
      and subspecies diversification rate are found to exhibit low phylogenetic signal,
      meaning that closely related species do not tend to possess similar numbers of
      subspecies. As predicted by theory, high subspecies richness was associated with
      large breeding range size, island dwelling, inhabitation of montane regions,
      habitat heterogeneity, and low latitude. Of these factors, breeding range size
      was the variable that explained the most variation. Unravelling whether species
      that have invaded previously glacial areas have more or fewer subspecies than
      expected proves to be complicated due to a covariation between the postglacial
      colonization, latitude, geographic range size, and subspecies richness. However,
      the effect of postglacial colonization on subspecies richness appears to be
      small. Mapping the distribution of species' subspecies richness globally reveals
      geographical patterns that correspond to many of the predictions of the
      statistical models, but may also reflect geographical variation in taxonomic
      practice. Overall, we demonstrate that biogeographic models can explain about 30%
      of the global variation in subspecies richness in birds.

PMID- 17439624
TI  - Drifting propagules and receding swamps: genetic footprints of mangrove
      recolonization and dispersal along tropical coasts.
AB  - Two issues that have captured the attention of tropical plant evolutionary
      biologists in recent years are the relative role of long distance dispersal (LDD)
      over vicariance in determining plant distributions and debate about the extent
      that Quaternary climatic changes affected tropical species. Propagules of some
      mangrove species are assumed to be capable of LDD due to their ability to float
      and survive for long periods of time in salt water. Mangrove species responded to
      glaciations with a contraction of their range. Thus, widespread mangrove species
      are an ideal system to study LDD and recolonization in the tropics. We present
      phylogenetic and phylogeographic analyses based on internal transcribed spacers
      region (ITS) sequences, chloroplast DNA (cpDNA), and amplified fragment length
      polymorphisms (AFLPs) of genomic DNA that demonstrate recent LDD across the
      Atlantic, rejecting the hypothesis of vicariance for the widespread distribution
      of the black mangrove (Avicennia germinans). Northern latitude populations likely
      became extinct during the late Quaternary due to frosts and aridification; these
      locations were recolonized afterward from southern populations. In some low
      latitude regions populations went extinct or were drastically reduced during the
      Quaternary because of lack of suitable habitat as sea levels changed. Our
      analyses show that low latitude Pacific populations of A. germinans harbor more
      diversity and reveal deeper divergence than Atlantic populations. Implications
      for our understanding of phylogeography of tropical species are discussed.

PMID- 17439625
TI  - Estimation of the number of individuals founding colonized populations.
AB  - A method for estimating the number of founding chromosomes in an isolated
      population is introduced. The method assumes that n/2 diploid individuals are
      sampled from a population and that alleles are identified at L unlinked loci. The
      population is assumed to have been founded T generations in the past by
      individuals carrying c chromosomes drawn randomly from a known source population,
      which has also been sampled. If c is small and the population grew rapidly after
      it was founded, accurate estimates of c can be obtained and those estimates are
      not sensitive to details of the history of population sizes. If c is larger or
      the population remained small after it was founded, then estimates of c depend on
      the history of population sizes. We test the performance of our method on
      simulated data and demonstrate its use on data from a rainbow trout (Oncorhynchus
      mykiss) population.

PMID- 17439626
TI  - A new hypothesis for the evolution of overproduction of ovules: an advantage of
      selective abortion for females not associated with variation in genetic quality
      of the resulting seeds.
AB  - A new hypothesis for the evolution of overproduction of ovules within flowers is
      proposed: overproduction is a counter-strategy of female seed production in the
      conflict with males and/or offspring. It is advantageous for females to produce a
      uniform size of seeds, whereas it is advantageous for fertilized ovules to absorb
      more resources than this size. If there is a variance in resource absorption
      ability among fertilized ovules, nonuniform seeds are produced. Then, by
      overproducing ovules, females should select fertilized ovules with similar
      resource absorption rates, resulting in seeds of uniform size. A model analysis
      confirmed that this hypothesis works. In the model, the fertilized ovules of a
      plant consist of two genotypes that differ in resource absorption rate. I found
      that overproduction of ovules and selective abortion is advantageous if the
      difference in the resource absorption rates of the genotypes is large. The new
      hypothesis is different from the selective abortion hypothesis in that selecting
      ovules is advantageous even if there are no differences in the genetic quality of
      resulting seeds.

PMID- 17439627
TI  - Testing for heparin-induced thrombocytopenia: are we there yet?

PMID- 17439628
TI  - von Willebrand factor/factor VIII concentrate (Haemate P) dosing based on
      pharmacokinetics: a prospective multicenter trial in elective surgery.
AB  - BACKGROUND: While plasma-derived concentrates containing large amounts of von
      Willebrand factor (VWF) are effective in treating von Willebrand disease (VWD),
      optimal dosing remains to be fully characterized. OBJECTIVES: To determine the
      feasibility of dosing Haemate P VWF/factor VIII (FVIII) concentrate based on
      pharmacokinetics (PK) in the management of surgical subjects with VWD. METHODS:
      VWD subjects scheduled for elective surgery were enrolled in a prospective
      multicenter open-label cohort study. A pre-operative loading dose of VWF/FVIII
      concentrate based upon prior individual subject PK analysis was administered
      followed by postoperative therapeutic/maintenance infusions. RESULTS: Twenty
      eight subjects with types 1, 2A or 3 VWD and one with type 2 M were enrolled.
      Median in vivo recovery of VWF ristocetin cofactor (VWF:RCo) was 1.9 IU dL(-1)
      (IU kg(-1))(-1) with an interquartile range (IQR) of 1.6-2.5 IU dL(-1) (IU kg(
      1))(-1). Median response, half-life and clearance were 74.0% (IQR, 55.5-100%),
      15.6 h (IQR, 9.0-28.4 h) and 3.26 mL kg(-1) h(-1) (IQR, 2.29-5.21 mL kg(-1) h(
      1)), respectively. A PK-guided median VWF:RCo loading dose of 62.4 IU kg(-1)
      (IQR, 50.1-87.0 IU kg(-1)) was administered. Postoperative mean trough VWF:RCo
      levels of 62-73 IU dL(-1) were sufficient to prevent bleeding. Investigators
      rated hemostasis excellent or good in 96.3% of subjects on the day of surgery and
      100% on the next day and on day 14. A subject with multiple risk factors
      developed pulmonary embolism, which resolved without sequelae. CONCLUSIONS:
      Haemate P provided effective and safe hemostasis in VWD subjects undergoing
      elective surgery. Selection of Haemate P loading dose on the basis of VWF PK
      proved feasible.

PMID- 17439629
TI  - Reactive site-dependent phenotypic alterations in plasminogen activator inhibitor
      1 transgenic mice.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is the major physiological
      inhibitor of plasminogen activators (PAs) and plays a role in the regulation of a
      number of physiological processes including the degradation of extracellular
      matrix proteins, cell proliferation and migration, and intracellular signaling.
      AIM: To characterize the effects of durable expression of a stable form of human
      PAI-1 and to characterize important structure-function relationships in PAI-1 in
      vivo. METHODS: We developed transgenic mice lines overexpressing stable variants
      of human PAI-1 under the control of the murine preproendothelin-1 promoter and
      characterized the phenotypic alterations displayed by transgenic mice. RESULTS:
      Transgenic mice expressing an active form of human PAI-1 (PAI-1-stab) display
      complex phenotypic abnormalities including alopecia and hepatosplenomegaly.
      Reactive site mutant transgenic mice expressing inactive PAI-1 exhibit complete
      phenotypic rescue, while transgenic mice expressing PAI-1 with reduced affinity
      for vitronectin manifest all of the phenotypic abnormalities present in PAI-1
      stab transgenic mice. CONCLUSIONS: The protease inhibitory activity of PAI-1
      toward PAs and/or other serine proteases is necessary and sufficient to promote
      complex phenotypic abnormalities and mediates many of the physiological effects
      of PAI-1 in vivo.

PMID- 17439630
TI  - Outcome of the subsequent pregnancy after a first loss in women with the factor V
      Leiden or prothrombin 20210A mutations.
AB  - BACKGROUND: The factor V Leiden (FVL) and prothrombin 20210A (PTm) mutations are
      associated with single late pregnancy loss and recurrent early pregnancy loss.
      The prognosis after an initial loss in women with thrombophilia is uncertain.
      OBJECTIVE: To assess the pregnancy outcome of the second pregnancy after a first
      loss in women with and without either FVL or PTm mutations. METHODS: We selected
      women with a first pregnancy loss out of two family cohorts of first degree
      relatives of probands with FVL or PTm mutations and a history of documented
      venous thromboembolism or premature atherosclerosis. RESULTS: Ninety-three women
      had had a first pregnancy loss and became pregnant a second time. Their risk of
      loss of the subsequent pregnancy was higher than in 825 women with a successful
      first pregnancy [25 vs. 12%, relative risk (RR) 2.0, 95% CI 1.4-3.0]. The live
      birth rate of the second pregnancy after an early first loss (<or= 12 weeks of
      gestation) was 77% (95% CI 62-87) for carriers and 76% (95% CI 57-89) for non
      carriers (RR 1.0, 95% CI 0.8-1.3). After a late first loss (> 12 weeks), the live
      birth rates were 68% (95% CI 46-85) and 80% (95% CI 49-94) for carriers and non
      carriers, respectively (RR 0.9, 95% CI 0.5-1.3). CONCLUSIONS: Women with a first
      pregnancy loss have a 2-fold increased risk of loss of the subsequent pregnancy,
      regardless of their carrier status. More importantly, the outcome of the second
      pregnancy is rather favorable in absolute terms, even for those with
      thrombophilia and a late loss, which raises concern regarding the risks and
      presumed benefits of anticoagulant therapy in these women.

PMID- 17439631
TI  - What is the clinical impact of low plasminogen activator inhibitor-1 (PAI-1)
      activity? A case report and study of the incidence of low PAI-1 antigen in a
      healthy population.

PMID- 17439632
TI  - Autoantibodies against endothelial protein C receptor and the risk of a first
      deep vein thrombosis.
AB  - BACKGROUND: The endothelial protein C receptor (EPCR) binds protein C and
      enhances its activation. Anti-EPCR autoantibodies are found in patients with
      antiphospholipid syndrome and may explain the increased risk of thrombosis in
      these patients. Anti-EPCR autoantibodies have been associated with fetal death
      and myocardial infarction in young women. OBJECTIVES: To determine whether anti
      EPCR autoantibodies are associated with deep vein thrombosis (DVT).
      PATIENTS/METHODS: We measured plasma anti-EPCR autoantibody levels in the Leiden
      Thrombophilia Study (LETS), a population-based case-control study consisting of
      474 patients with a first DVT and 474 control subjects. RESULTS: The estimated
      risk of DVT was increased approximately 2-fold in the presence of elevated IgA,
      IgG or IgM anti-EPCR autoantibodies (i.e. levels above the 90th percentile as
      measured in the control subjects). The risk conferred by anti-EPCR increased in a
      dose-dependent manner for IgA and IgG. When anti-EPCR autoantibodies were
      considered in the co-presence of lupus anticoagulant (LAC) the odds ratio (OR)
      was 6.1 [95% CI 1.3-27.9]. Anti-EPCR without LAC remained associated with DVT (OR
      1.6; 95% CI 1.2-2.1). Anti-EPCR autoantibodies were associated with high levels
      of D-dimer and soluble EPCR in controls, suggestive of a prothrombotic status
      induced by the autoantibodies. CONCLUSIONS: This study demonstrates that the
      presence of anti-EPCR autoantibodies is a moderate risk factor for DVT in the
      general population.

PMID- 17439633
TI  - Quality of oral anticoagulant treatment and risk of subsequent recurrent
      thromboembolism in patients with deep vein thrombosis.

PMID- 17439634
TI  - Acute respiratory tract infections in elderly patients increase systemic levels
      of hemostatic proteins.

PMID- 17439635
TI  - Genotype variation and capsular serotypes of Porphyromonas gingivalis from
      chronic periodontitis and periodontal abscesses.
AB  - Porphyromonas gingivalis is considered an important pathogen in periodontal
      disease. While this organism expresses a number of virulence factors, no study
      combining different virulence polymorphisms has, so far, been conducted. The
      occurrence of combined virulence (Cv) genotypes in 62 isolates of P. gingivalis
      was investigated from subjects displaying either chronic periodontitis or
      periodontal abscess. The Cv genotypes, based on gene variation of fimbriae
      (fimA), Lys-specific cystein proteinase (kgp) and Arg-specific cystein proteinase
      (prpR1/rgpA), were evaluated by PCR. The isolates were also subjected to capsular
      polysaccharide K-serotyping. A total of 18 Cv genotype variants based on fimA:
      kgp: rgpA were identified, of which II:I:A and II:II:A Cv genotypes (53.3%) were
      the two most frequently detected combinations. Moreover, 36% of the isolates were
      K-typeable, with the K6 serotype being the most prevalent (23%). Two isolates had
      the same genotype as the virulent strain W83. The results indicate that chronic
      periodontitis is not associated with a particularly virulent clonal type. A
      highly virulent genotype (e.g. strain W83) of P. gingivalis can be found in
      certain periodontitis patients.

PMID- 17439636
TI  - Purification and biochemical characterization of an extracellular beta
      glucosidase from the wood-decaying fungus Daldinia eschscholzii (Ehrenb.:Fr.)
      Rehm.
AB  - An extracellular beta-glucosidase was purified from culture filtrates of the wood
      decaying fungus Daldinia eschscholzii (Ehrenb.:Fr.) Rehm grown on 1.0% (w/v)
      carboxymethyl-cellulose using ammonium sulfate precipitation, ion-exchange,
      hydrophobic interaction and gel filtration chromatography. The enzyme is
      monomeric with a molecular weight of 64.2 kDa as estimated by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis, and has a pI of 8.55. The enzyme
      catalyzes the hydrolysis of p-nitrophenyl-beta-D-glucopyranoside (PNPG) as the
      substrate, with a K(m) of 1.52 mM, and V(max) of 3.21 U min mg(-1) protein.
      Glucose competitively inhibited beta-glucosidase with a K(i) value of 0.79 mM.
      Optimal activity with PNPG as the substrate was at pH 5.0 and 50 degrees C. The
      enzyme was stable at pH 5.0 at temperatures up to 50 degrees C. The purified beta
      glucosidase was active against PNPG, cellobiose, sophorose, laminaribiose and
      gentiobiose, but did not hydrolyze lactose, sucrose, Avicel or o-nitrophenyl-beta
      d-galactopyranoside. The activity of beta-glucosidase was stimulated by Ca(2+),
      Co(2+), Mg(2+), Mn(2+), glycerol, dimethyl sulfoxide (DMSO), dithiothreitol and
      EDTA, and strongly inhibited by Hg(2+). The internal amino acid sequences of D.
      eschscholziibeta-glucosidase have similarity to the sequences of the family 3
      beta-glucosyl hydrolase.

PMID- 17439637
TI  - Phosphorylation of Type IA restriction-modification complex enzyme EcoKI on the
      HsdR subunit.
AB  - Phosphorylation of Type I restriction-modification (R-M) enzymes EcoKI, EcoAI,
      and EcoR124I - representatives of IA, IB, and IC families, respectively - was
      analysed in vivo by immunoblotting of endogenous phosphoproteins isolated from
      Escherichia coli strains harbouring the corresponding hsd genes, and in vitro by
      a phosphorylation assay using protein kinase present in subcellular fractions of
      E. coli. From all three R-M enzymes, the HsdR subunit of EcoKI system was the
      only subunit that was phosphorylated. Further, evidence is presented that HsdR is
      phosphorylated in vivo only when coproduced with HsdM and HsdS subunits - as part
      of assembled EcoKI restriction endonuclease, while the individually produced HsdR
      subunit is not phosphorylated. In vitro phosphorylation of the HsdR subunit of
      purified EcoKI endonuclease occurs on Thr, and is strictly dependent on the
      addition of a catalytic amount of cytoplasmic fraction isolated from E. coli. So
      far this is the first case of phosphorylation of a Type I R-M enzyme reported.

PMID- 17439638
TI  - Studies of the organization of the human nociceptive withdrawal reflex. Focus on
      sensory convergence and stimulation site dependency.

PMID- 17439639
TI  - Changes of the prescription of hormone therapy in menopausal women: an
      observational study in Taiwan.
AB  - BACKGROUND: To evaluate the impact of the 2002 Women's Health Initiative (WHI)
      study results on the prescription of menopausal hormone therapy (MHT) to treat
      menopause-related symptoms in Taiwan. METHODS: This retrospective study
      participant data collected from women interviewed in 2001 Taiwan's National
      Health Interview Survey (NHIS) and the National Health Insurance (NHI) outpatient
      claims for women being treated for menopause-related symptoms. We compared
      prescriptions made for MHI to women seeking outpatient treatment for menopause
      related symptoms before and after the publication of the 2002 WHI to study its
      effect of prescription behavior in Taiwan. There was one dichotomous outcome
      variable, which was whether MHT was prescribed or not in an outpatient visit to
      treat menopause-related symptoms. RESULTS: Our study included 504 women 45 years
      old or above whose outpatient visits for menopause-related symptoms were covered
      by National Health Insurance in 2002. In total, these 504 women made 2549
      outpatient visits to be treated for these symptoms. The proportion of outpatient
      visits in which MHT was prescribed dropped from 83.0% (n = 1,155) before WHI to
      73.0% (n = 844) after WHI. We found a decrease in likelihood that women would be
      prescribed MHT for menopause-related symptoms after the release of the WHI report
      (OR = 0.36, 95% CI = 0.25 to 0.52, p < 0.05). Gynecologists and obstetricians are
      more likely to prescribe MHT than physicians with other medical specialties
      (5.34; 95% CI = 3.45 to 8.26, p < 0.05). Women with college level educations or
      higher became less likely to be prescribed MHT (Model 2; OR 0.30; 95% CI 0.11
      0.83), and academic medical centers became less likely to prescribe MHT than
      other medical care institutions (Model 3; OR 0.15; 95% CI 0.34-0.63). CONCLUSION:
      The WHI report caused a substantial decline in the use of MHT to treat menopause
      related symptoms in Taiwan. It was found to exert most of its influence in
      patients with higher educations, physicians with specialties other than
      gynecologists and obstetricians, and academic medical centers.

PMID- 17439640
TI  - Evolutionary proteomics identifies amino acids essential for ligand-binding of
      the cytokinin receptor CHASE domain.
AB  - BACKGROUND: In plants the hormone cytokinin is perceived by members of a small
      cytokinin receptor family, which are hybrid sensor histidine kinases. While the
      immediate downstream signaling pathway is well characterized, the domain of the
      receptor responsible for ligand binding and which residues are involved in this
      process has not been determined experimentally. RESULTS: Using a live cell
      hormone-binding assay, we show that cytokinin is bound by a receptor domain
      predicted to be extracellular, the so called CHASE (cyclases, histidine kinase
      associated sensory extracellular) domain. The CHASE domain occurs not only in
      plant cytokinin receptors but also in numerous orphan receptors in lower
      eukaryotes and bacteria. Taking advantage of this fact, we used an evolutionary
      proteomics approach to identify amino acids important for cytokinin binding by
      looking for residues conserved in cytokinin receptors, but not in other
      receptors. By comparing differences in evolutionary rates, we predicted five
      amino acids within the plant CHASE domains to be crucial for cytokinin binding.
      Mutagenesis of the predicted sites and subsequent binding assays confirmed the
      relevance of four of the selected amino acids, showing the biological
      significance of site-specific evolutionary rate differences. CONCLUSION: This
      work demonstrates the use of a bioinformatic analysis to mine the huge set of
      genomic data from different taxa in order to generate a testable hypothesis. We
      verified the hypothesis experimentally and identified four amino acids which are
      to a different degree required for ligand-binding of a plant hormone receptor.

PMID- 17439641
TI  - The evolution of the vertebrate metzincins; insights from Ciona intestinalis and
      Danio rerio.
AB  - BACKGROUND: The metzincins are a large gene superfamily of proteases
      characterized by the presence of a zinc protease domain, and include the ADAM,
      ADAMTS, BMP1/TLL, meprin and MMP genes. Metzincins are involved in the
      proteolysis of a wide variety of proteins, including those of the extracellular
      matrix. The metzincin gene superfamily comprises eighty proteins in the human
      genome and ninety-three in the mouse. When and how the level of complexity
      apparent in the vertebrate metzincin gene superfamily arose has not been
      determined in detail. Here we present a comprehensive analysis of vertebrate
      metzincins using genes from both Ciona intestinalis and Danio rerio to provide
      new insights into the complex evolution of this gene superfamily. RESULTS: We
      have identified 19 metzincin genes in the ciona genome and 83 in the zebrafish
      genome. Phylogenetic analyses reveal that the expansion of the metzincin gene
      superfamily in vertebrates has occurred predominantly by the simple duplication
      of pre-existing genes rather than by the appearance and subsequent expansion of
      new metzincin subtypes (the only example of which is the meprin gene family).
      Despite the number of zebrafish metzincin genes being relatively similar to that
      of tetrapods (e.g. man and mouse), the pattern of gene retention and loss within
      these lineages is markedly different. In addition, we have studied the evolution
      of the related TIMP gene family and identify a single ciona and four zebrafish
      TIMP genes. CONCLUSION: The complexity seen in the vertebrate metzincin gene
      families was mainly acquired during vertebrate evolution. The metzincin gene
      repertoire in protostomes and invertebrate deuterostomes has remained relatively
      stable. The expanded metzincin gene repertoire of extant tetrapods, such as man,
      has resulted largely from duplication events associated with early vertebrate
      evolution, prior to the sarcopterygian-actinopterygian split. The teleost
      repertoire of metzincin genes in part parallels that of tetrapods but has been
      significantly modified, perhaps as a consequence of a teleost-specific
      duplication event.

PMID- 17439642
TI  - From perception to action: phase-locked gamma oscillations correlate with
      reaction times in a speeded response task.
AB  - BACKGROUND: Phase-locked gamma oscillations have so far mainly been described in
      relation to perceptual processes such as sensation, attention or memory matching.
      Due to its very short latency ( approximately 90 ms) such oscillations are a
      plausible candidate for very rapid integration of sensory and motor processes.
      RESULTS: We measured EEG in 13 healthy participants in a speeded reaction task.
      Participants had to press a button as fast as possible whenever a visual stimulus
      was presented. The stimulus was always identical and did not have to be
      discriminated from other possible stimuli. In trials in which the participants
      showed a fast response, a slow negative potential over central electrodes
      starting approximately 800 ms before the response and highly phase-locked gamma
      oscillations over central and posterior electrodes between 90 and 140 ms after
      the stimulus were observed. In trials in which the participants showed a slow
      response, no slow negative potential was observed and phase-locked gamma
      oscillations were significantly reduced. Furthermore, for slow response trials
      the phase-locked gamma oscillations were significantly delayed with respect to
      fast response trials. CONCLUSION: These results indicate the relevance of phase
      locked gamma oscillations for very fast (not necessarily detailed) integration
      processes.

PMID- 17439643
TI  - diArk--a resource for eukaryotic genome research.
AB  - BACKGROUND: The number of completed eukaryotic genome sequences and cDNA projects
      has increased exponentially in the past few years although most of them have not
      been published yet. In addition, many microarray analyses yielded thousands of
      sequenced EST and cDNA clones. For the researcher interested in single gene
      analyses (from a phylogenetic, a structural biology or other perspective) it is
      therefore important to have up-to-date knowledge about the various resources
      providing primary data. DESCRIPTION: The database is built around 3 central
      tables: species, sequencing projects and publications. The species table contains
      commonly and alternatively used scientific names, common names and the complete
      taxonomic information. For projects the sequence type and links to species
      project web-sites and species homepages are stored. All publications are linked
      to projects. The web-interface provides comprehensive search modules with
      detailed options and three different views of the selected data. We have
      especially focused on developing an elaborate taxonomic tree search tool that
      allows the user to instantaneously identify e.g. the closest relative to the
      organism of interest. CONCLUSION: We have developed a database, called diArk, to
      store, organize, and present the most relevant information about completed genome
      projects and EST/cDNA data from eukaryotes. Currently, diArk provides information
      about 415 eukaryotes, 823 sequencing projects, and 248 publications.

PMID- 17439644
TI  - A full Bayesian hierarchical mixture model for the variance of gene differential
      expression.
AB  - BACKGROUND: In many laboratory-based high throughput microarray experiments,
      there are very few replicates of gene expression levels. Thus, estimates of gene
      variances are inaccurate. Visual inspection of graphical summaries of these data
      usually reveals that heteroscedasticity is present, and the standard approach to
      address this is to take a log2 transformation. In such circumstances, it is then
      common to assume that gene variability is constant when an analysis of these data
      is undertaken. However, this is perhaps too stringent an assumption. More careful
      inspection reveals that the simple log2 transformation does not remove the
      problem of heteroscedasticity. An alternative strategy is to assume independent
      gene-specific variances; although again this is problematic as variance estimates
      based on few replications are highly unstable. More meaningful and reliable
      comparisons of gene expression might be achieved, for different conditions or
      different tissue samples, where the test statistics are based on accurate
      estimates of gene variability; a crucial step in the identification of
      differentially expressed genes. RESULTS: We propose a Bayesian mixture model,
      which classifies genes according to similarity in their variance. The result is
      that genes in the same latent class share the similar variance, estimated from a
      larger number of replicates than purely those per gene, i.e. the total of all
      replicates of all genes in the same latent class. An example dataset, consisting
      of 9216 genes with four replicates per condition, resulted in four latent classes
      based on their similarity of the variance. CONCLUSION: The mixture variance model
      provides a realistic and flexible estimate for the variance of gene expression
      data under limited replicates. We believe that in using the latent class
      variances, estimated from a larger number of genes in each derived latent group,
      the p-values obtained are more robust than either using a constant gene or gene
      specific variance estimate.

PMID- 17439645
TI  - Patient adherence to medical treatment: a review of reviews.
AB  - BACKGROUND: Patients' non-adherence to medical treatment remains a persistent
      problem. Many interventions to improve patient adherence are unsuccessful and
      sound theoretical foundations are lacking. Innovations in theory and practice are
      badly needed. A new and promising way could be to review the existing reviews of
      adherence to interventions and identify the underlying theories for effective
      interventions. That is the aim of our study. METHODS: The study is a review of 38
      systematic reviews of the effectiveness of adherence interventions published
      between 1990 and 2005. Electronic literature searches were conducted in Medline,
      Psychinfo, Embase and the Cochrane Library. Explicit inclusion and exclusion
      criteria were applied. The scope of the study is patient adherence to medical
      treatment in the cure and care sector. RESULTS: Significant differences in the
      effectiveness of adherence interventions were found in 23 of the 38 systematic
      reviews. Effective interventions were found in each of four theoretical
      approaches to adherence interventions: technical, behavioural, educational and
      multi-faceted or complex interventions. Technical solutions, such as a
      simplification of the regimen, were often found to be effective, although that
      does not count for every therapeutic regimen.Overall, our results show that,
      firstly, there are effective adherence interventions without an explicit
      theoretical explanation of the operating mechanisms, for example technical
      solutions. Secondly, there are effective adherence interventions, which clearly
      stem from the behavioural theories, for example incentives and reminders.
      Thirdly, there are other theoretical models that seem plausible for explaining
      non-adherence, but not very effective in improving adherence behaviour. Fourthly,
      effective components within promising theories could not be identified because of
      the complexity of many adherence interventions and the lack of studies that
      explicitly compare theoretical components. CONCLUSION: There is a scarcity of
      comparative studies explicitly contrasting theoretical models or their
      components. The relative weight of these theories and the effective components in
      the interventions designed to improve adherence, need to be assessed in future
      studies.

PMID- 17439646
TI  - Beta-D-glucoside utilization by Mycoplasma mycoides subsp. mycoides SC: possible
      involvement in the control of cytotoxicity towards bovine lung cells.
AB  - BACKGROUND: Contagious bovine pleuropneumonia (CBPP) caused by Mycoplasma
      mycoides subsp. mycoides small-colony type (SC) is among the most serious threats
      for livestock producers in Africa. Glycerol metabolism-associated H2O2 production
      seems to play a crucial role in virulence of this mycoplasma. A wide number of
      attenuated strains of M. mycoides subsp. mycoides SC are currently used in Africa
      as live vaccines. Glycerol metabolism is not affected in these vaccine strains
      and therefore it does not seem to be the determinant of their attenuation. A non
      synonymous single nucleotide polymorphism (SNP) in the bgl gene coding for the 6
      phospho-beta-glucosidase (Bgl) has been described recently. The SNP
      differentiates virulent African strains isolated from outbreaks with severe CBPP,
      which express the Bgl isoform Val204, from strains to be considered less virulent
      isolated from CBPP outbreaks with low mortality and vaccine strains, which
      express the Bgl isoform Ala204. RESULTS: Strains of M. mycoides subsp. mycoides
      SC considered virulent and possessing the Bgl isoform Val204, but not strains
      with the Bgl isoform Ala204, do trigger elevated levels of damage to embryonic
      bovine lung (EBL) cells upon incubation with the disaccharides (i.e., beta-D
      glucosides) sucrose and lactose. However, strains expressing the Bgl isoform
      Val204 show a lower hydrolysing activity on the chromogenic substrate p
      nitrophenyl-beta-D-glucopyranoside (pNPbG) when compared to strains that possess
      the Bgl isoform Ala204. Defective activity of Bgl in M. mycoides subsp. mycoides
      SC does not lead to H2O2 production. Rather, the viability during addition of
      beta-D-glucosides in medium-free buffers is higher for strains harbouring the Bgl
      isoform Val204 than for those with the isoform Ala204. CONCLUSION: Our results
      indicate that the studied SNP in the bgl gene is one possible cause of the
      difference in bacterial virulence among strains of M. mycoides subsp. mycoides
      SC. Bgl does not act as a direct virulence factor, but strains possessing the Bgl
      isoform Val204 with low hydrolysing activity are more prone to survive in
      environments that contain high levels of beta-D-glucosides, thus contributing in
      some extent to mycoplasmaemia.

PMID- 17439647
TI  - Are liver and renal lesions in East Greenland polar bears (Ursus maritimus)
      associated with high mercury levels?
AB  - BACKGROUND: In the Arctic, polar bears (Ursus maritimus) bio-accumulate mercury
      as they prey on polluted ringed seals (Phoca hispida) and bearded seals
      (Erignathus barbatus). Studies have shown that polar bears from East Greenland
      are among the most mercury polluted species in the Arctic. It is unknown whether
      these levels are toxic to liver and kidney tissue. METHODS: We investigated the
      histopathological impact from anthropogenic long-range transported mercury on
      East Greenland polar bear liver (n = 59) and kidney (n = 57) tissues. RESULTS:
      Liver mercury levels ranged from 1.1-35.6 microg/g wet weight and renal levels
      ranged from 1-50 microg/g wet weight, of which 2 liver values and 9 kidney values
      were above known toxic threshold level of 30 microg/g wet weight in terrestrial
      mammals. Evaluated from age-correcting ANCOVA analyses, liver mercury levels were
      significantly higher in individuals with visible Ito cells (p < 0.02) and a
      similar trend was found for lipid granulomas (p = 0.07). Liver mercury levels
      were significantly lower in individuals with portal bile duct
      proliferation/fibrosis (p = 0.007) and a similar trend was found for proximal
      convoluted tubular hyalinisation in renal tissue (p = 0.07). CONCLUSION: Based on
      these relationships and the nature of the chronic inflammation we conclude that
      the lesions were likely a result of recurrent infections and ageing but that long
      term exposure to mercury could not be excluded as a co-factor. The information is
      important as it is likely that tropospheric mercury depletion events will
      continue to increase the concentrations of this toxic heavy metal in the Sub
      Arctic and Arctic marine food webs.

PMID- 17439648
TI  - Polymeric nanoparticle-encapsulated curcumin ("nanocurcumin"): a novel strategy
      for human cancer therapy.
AB  - BACKGROUND: Curcumin, a yellow polyphenol extracted from the rhizome of turmeric
      (Curcuma longa), has potent anti-cancer properties as demonstrated in a plethora
      of human cancer cell line and animal carcinogenesis models. Nevertheless,
      widespread clinical application of this relatively efficacious agent in cancer
      and other diseases has been limited due to poor aqueous solubility, and
      consequently, minimal systemic bioavailability. Nanoparticle-based drug delivery
      approaches have the potential for rendering hydrophobic agents like curcumin
      dispersible in aqueous media, thus circumventing the pitfalls of poor solubility.
      RESULTS: We have synthesized polymeric nanoparticle encapsulated formulation of
      curcumin - nanocurcumin - utilizing the micellar aggregates of cross-linked and
      random copolymers of N-isopropylacrylamide (NIPAAM), with N-vinyl-2-pyrrolidone
      (VP) and poly(ethyleneglycol)monoacrylate (PEG-A). Physico-chemical
      characterization of the polymeric nanoparticles by dynamic laser light scattering
      and transmission electron microscopy confirms a narrow size distribution in the
      50 nm range. Nanocurcumin, unlike free curcumin, is readily dispersed in aqueous
      media. Nanocurcumin demonstrates comparable in vitro therapeutic efficacy to free
      curcumin against a panel of human pancreatic cancer cell lines, as assessed by
      cell viability and clonogenicity assays in soft agar. Further, nanocurcumin's
      mechanisms of action on pancreatic cancer cells mirror that of free curcumin,
      including induction of cellular apoptosis, blockade of nuclear factor kappa B
      (NFkappaB) activation, and downregulation of steady state levels of multiple pro
      inflammatory cytokines (IL-6, IL-8, and TNFalpha). CONCLUSION: Nanocurcumin
      provides an opportunity to expand the clinical repertoire of this efficacious
      agent by enabling ready aqueous dispersion. Future studies utilizing nanocurcumin
      are warranted in pre-clinical in vivo models of cancer and other diseases that
      might benefit from the effects of curcumin.

PMID- 17439649
TI  - Molecular biogeography of Europe: Pleistocene cycles and postglacial trends.
AB  - The climatic cycles with subsequent glacial and intergalcial periods have had a
      great impact on the distribution and evolution of species. Using genetic
      analytical tools considerably increased our understanding of these processes. In
      this review I therefore give an overview of the molecular biogeography of Europe.
      For means of simplification, I distinguish between three major biogeographical
      entities: (i) "Mediterranean" with Mediterranean differentiation and dispersal
      centres, (ii) "Continental" with extra-Mediterranean centres and (iii) "Alpine"
      and/or "Arctic" with recent alpine and/or arctic distribution patterns. These
      different molecular biogeographical patterns are presented using actual examples.
      Many "Mediterranean" species are differentiated into three major European genetic
      lineages, which are due to glacial isolation in the three major Mediterranean
      peninsulas. Postglacial expansion in this group of species is mostly influenced
      by the barriers of the Pyrenees and the Alps with four resulting main patterns of
      postglacial range expansions. However, some cases are known with less than one
      genetic lineage per Mediterranean peninsula on the one hand, and others with a
      considerable genetic substructure within each of the Mediterranean peninsulas,
      Asia Minor and the Maghreb. These structures within the Mediterranean sub-centres
      are often rather strong and in several cases even predate the Pleistocene. For
      the "Continental" species, it could be shown that the formerly supposed
      postglacial spread from eastern Palearctic expansion centres is mostly not
      applicable. Quite the contrary, most of these species apparently had extra
      Mediterranean centres of survival in Europe with special importance of the
      perialpine regions, the Carpathian Basin and parts of the Balkan Peninsula. In
      the group of "Alpine" and/or "Arctic" species, several molecular biogeographical
      patterns have been found, which support and improve the postulates based on
      distribution patterns and pollen records. Thus, genetic studies support the
      strong linkage between southwestern Alps and Pyrenees, northeastern Alps and
      Carpathians as well as southeastern Alps and the Dinaric mountain systems, hereby
      allowing conclusions on the glacial distribution patterns of these species.
      Furthermore, genetic analyses of arctic-alpine disjunct species support their
      broad distribution in the periglacial areas at least during the last glacial
      period. The detailed understanding of the different phylogeographical structures
      is essential for the management of the different evolutionary significant units
      of species and the conservation of their entire genetic diversity. Furthermore,
      the distribution of genetic diversity due to biogeographical reasons helps
      understanding the differing regional vulnerabilities of extant populations.

PMID- 17439650
TI  - Selection for tameness modulates the expression of heme related genes in silver
      foxes.
AB  - BACKGROUND: The genetic and molecular mechanisms of tameness are largely unknown.
      A line of silver foxes (Vulpes vulpes) selected for non-aggressive behavior has
      been used in Russia since the 1960's to study the effect of domestication. We
      have previously compared descendants of these selected (S) animals with a group
      of non-selected (NS) silver foxes kept under identical conditions, and showed
      that changes in the brain transcriptome between the two groups are small.
      Unexpectedly, many of the genes showing evidence of differential expression
      between groups were related to hemoproteins. RESULTS: In this study, we use
      quantitative RT-PCR to demonstrate that the activity of heme related genes differ
      between S and NS foxes in three regions of the brain. Furthermore, our analyses
      also indicate that changes in mRNA levels of heme related genes can be well
      described by an additive polygenic effect. We also show that the difference in
      genetic background between the two lines of foxes is limited, as estimated by
      mitochondrial DNA divergence. CONCLUSION: Our results indicate that selection for
      tameness can modify the expression of heme related genes in canid brain regions
      known to modulate emotions and behavior. The possible involvement of heme related
      genes in behavior is surprising. It is possible that hemoglobin modulates the
      behavior of canids by interaction with CO and NO signaling. Another possibility
      is that hemorphins, known to be produced after enzymatic cleavage of hemoglobin,
      are responsible for behavioral alterations. Thus, we hypothesize that hemoglobin
      metabolism can be a functionally relevant aspect of the domestic phenotype in
      foxes selected for tameness.

PMID- 17439651
TI  - Knee kinematics and kinetics in former soccer players with a 16-year-old ACL
      injury--the effects of twelve weeks of knee-specific training.
AB  - BACKGROUND: Training of neuromuscular control has become increasingly important
      and plays a major role in rehabilitation of subjects with an injury to the
      anterior cruciate ligament (ACL). Little is known, however, of the influence of
      this training on knee stiffness during loading. Increased knee stiffness occurs
      as a loading strategy of ACL-injured subjects and is associated with increased
      joint contact forces. Increased or altered joint loads contribute to the
      development of osteoarthritis.The aim of the study was to determine if knee
      stiffness, defined by changes in knee kinetics and kinematics of gait, step
      activity and cross-over hop could be reduced through a knee-specific 12-week
      training programme. METHODS: A 3-dimensional motion analysis system (VICON) and a
      force plate (AMTI) were used to calculate knee kinetics and kinematics before and
      after 12 weeks of knee-specific training in 12 males recruited from a cohort with
      ACL injury 16 years earlier. Twelve uninjured males matched for age, sex, BMI and
      activity level served as a reference group. Self-reported patient-relevant data
      were obtained by the KOOS questionnaire. RESULTS: There were no significant
      changes in knee stiffness during gait and step activity after training. For the
      cross-over hop, increased peak knee flexion during landing (from 44 to 48
      degrees, p = 0.031) and increased internal knee extensor moment (1.28 to 1.55
      Nm/kg, p = 0.017) were seen after training, indicating reduced knee stiffness.
      The KOOS sport and recreation score improved from 70 to 77 (p = 0.005) and was
      significantly correlated with the changes in knee flexion during landing for the
      cross-over hop (r = 0.6, p = 0.039). CONCLUSION: Knee-specific training improved
      lower extremity kinetics and kinematics, indicating reduced knee stiffness during
      demanding hop activity. Self-reported sport and recreational function correlated
      positively with the biomechanical changes supporting a clinical importance of the
      findings. Further studies are needed to confirm these results in women and in
      other ACL injured populations.

PMID- 17439652
TI  - Cost-effectiveness of preventative therapies for postmenopausal women with
      osteopenia.
AB  - BACKGROUND: Limited data are available regarding the cost-effectiveness of
      preventative therapies for postmenopausal women with osteopenia. The objective of
      the present study was to evaluate the cost-effectiveness of raloxifene,
      alendronate and conservative care in this population. METHODS: We developed a
      microsimulation model to assess the incremental cost and effectiveness of
      raloxifene and alendronate relative to conservative care. We assumed a societal
      perspective and a lifetime time horizon. We examined clinical scenarios involving
      postmenopausal women from 55 to 75 years of age with bone mineral density T
      scores ranging from -1.0 to -2.4. Modeled health events included vertebral and
      nonvertebral fractures, invasive breast cancer, and venous thromboembolism (VTE).
      Raloxifene and alendronate were assumed to reduce the incidence of vertebral but
      not nonvertebral fractures; raloxifene was assumed to decrease the incidence of
      breast cancer and increase the incidence of VTEs. Cost-effectiveness is reported
      in $/QALYs gained. RESULTS: For women 55 to 60 years of age with a T-score of 
      1.8, raloxifene cost approximately $50,000/QALY gained relative to conservative
      care. Raloxifene was less cost-effective for women 65 and older. At all ages,
      alendronate was both more expensive and less effective than raloxifene. In most
      clinical scenarios, raloxifene conferred a greater benefit (in QALYs) from
      prevention of invasive breast cancer than from fracture prevention. Results were
      most sensitive to the population's underlying risk of fracture and breast cancer,
      assumed efficacy and costs of treatment, and the discount rate. CONCLUSION: For
      55 and 60 year old women with osteopenia, treatment with raloxifene compares
      favorably to interventions accepted as cost-effective.

PMID- 17439653
TI  - A single nucleotide mutation in Nppc is associated with a long bone abnormality
      in lbab mice.
AB  - BACKGROUND: The long bone abnormality (lbab) mouse is a new autosomal recessive
      mutant characterized by overall smaller body size with proportionate dwarfing of
      all organs and shorter long bones. Previous linkage analysis has located the lbab
      mutation on chromosome 1 between the markers D1Mit9 and D1Mit488. RESULTS: A
      genome-based positional approach was used to identify a mutation associated with
      lbab disease. A total of 122 genes and expressed sequence tags at the lbab region
      were screened for possible mutation by using genomic DNA from lbabl/lbab, lbab/+,
      and +/+ B6 mice and high throughput temperature gradient capillary
      electrophoresis. A sequence difference was identified in one of the amplicons of
      gene Nppc between lbab/lbab and +/+ mice. One-step reverse transcriptase
      polymerase chain reaction was performed to validate the difference of Nppc in
      different types of mice at the mRNA level. The mutation of Nppc was unique in
      lbab/lbab mice among multiple mouse inbred strains. The mutation of Nppc is co
      segregated with lbab disease in 200 progenies produced from heterozygous lbab/+
      parents. CONCLUSION: A single nucleotide mutation of Nppc is associated with
      dwarfism in lbab/lbab mice. Current genome information and technology allow us to
      efficiently identify single nucleotide mutations from roughly mapped disease
      loci. The lbab mouse is a useful model for hereditary human achondroplasia.

PMID- 17439654
TI  - On the functions of the h subunit of eukaryotic initiation factor 3 in late
      stages of translation initiation.
AB  - BACKGROUND: The eukaryotic translation initiation factor 3 (eIF3) has multiple
      roles during the initiation of translation of cytoplasmic mRNAs. How individual
      subunits of eIF3 contribute to the translation of specific mRNAs remains poorly
      understood, however. This is true in particular for those subunits that are not
      conserved in budding yeast, such as eIF3h. RESULTS: Working with stable reporter
      transgenes in Arabidopsis thaliana mutants, it was demonstrated that the h
      subunit of eIF3 contributes to the efficient translation initiation of mRNAs
      harboring upstream open reading frames (uORFs) in their 5' leader sequence.
      uORFs, which can function as devices for translational regulation, are present in
      over 30% of Arabidopsis mRNAs, and are enriched among mRNAs for transcriptional
      regulators and protein modifying enzymes. Microarray comparisons of polysome
      loading in wild-type and eif3h mutant seedlings revealed that eIF3h generally
      helps to maintain efficient polysome loading of mRNAs harboring multiple uORFs.
      In addition, however, eIF3h also boosted the polysome loading of mRNAs with long
      leaders or coding sequences. Moreover, the relative polysome loading of certain
      functional groups of mRNAs, including ribosomal proteins, was actually increased
      in the eif3h mutant, suggesting that regulons of translational control can be
      revealed by mutations in generic translation initiation factors. CONCLUSION: The
      intact eIF3h protein contributes to efficient translation initiation on 5' leader
      sequences harboring multiple uORFs, although mRNA features independent of uORFs
      are also implicated.

PMID- 17439655
TI  - Ulcerated calcification of the interventricular septum causing transient ischemic
      attacks: case report.
AB  - BACKGROUND: Calcific deposits are frequently observed at sites of healed
      myocardial infarcts. Grossly visible calcification of myocardial infarcts and
      calcified intracavitary cardiac thrombi are less common but recently are becoming
      more frequent findings during surgical ventricular restoration procedures. CASE
      PRESENTATION: A 64 year old male diabetic patient experienced two episodes of
      transient ischemic attacks during the last six months. During the diagnostic work
      up he was found to have triple vessel coronary artery disease with mild left
      ventricular dysfunction, akinesia of the anterior-apical wall and hypokinesia of
      the inferior wall. He was referred to our department for coronary artery bypass
      grafting. He underwent elective triple coronary artery bypass and a ventricular
      restoration procedure due to apical wall thinning. The inspection of the left
      ventricle revealed an ulcerated round shape calcification of the interventricular
      septum with a crater filled with clot. We resected the above lesion and covered
      the damaged area with the septal Dacron patch of the modified linear closure. The
      patient was discharged from the hospital on the 11th postoperative day and has
      been doing well 6 months later, with improvement in both ventricular function and
      clinical status. CONCLUSION: The exploration of the left ventricular cavity
      reveals interesting phases of the post-infarction healing process. The suspicion
      of left ventricular thrombosis in patients with ventricular asynergy justifies a
      ventricular exploration during coronary artery bypass surgery.

PMID- 17439656
TI  - The taxonomy of Enterobacter sakazakii: proposal of a new genus Cronobacter gen.
      nov. and descriptions of Cronobacter sakazakii comb. nov. Cronobacter sakazakii
      subsp. sakazakii, comb. nov., Cronobacter sakazakii subsp. malonaticus subsp.
      nov., Cronobacter turicensis sp. nov., Cronobacter muytjensii sp. nov.,
      Cronobacter dublinensis sp. nov. and Cronobacter genomospecies 1.
AB  - BACKGROUND: Enterobacter sakazakii is an opportunistic pathogen that can cause
      infections such as necrotizing enterocolitis, bacteraemia, meningitis and brain
      abscess/lesions. When the species was defined in 1980, 15 biogroups were
      described and it was suggested that these could represent multiple species. In
      this study the taxonomic relationship of strains described as E. sakazakii was
      further investigated. RESULTS: Strains identified as E. sakazakii were divided
      into separate groups on the basis of f-AFLP fingerprints, ribopatterns and full
      length 16S rRNA gene sequences. DNA-DNA hybridizations revealed five
      genomospecies. The phenotypic profiles of the genomospecies were determined and
      biochemical markers identified. CONCLUSION: This study clarifies the taxonomy of
      E. sakazakii and proposes a reclassification of these organisms.

PMID- 17439657
TI  - Bactericidal action of positive and negative ions in air.
AB  - BACKGROUND: In recent years there has been renewed interest in the use of air
      ionisers to control of the spread of airborne infection. One characteristic of
      air ions which has been widely reported is their apparent biocidal action.
      However, whilst the body of evidence suggests a biocidal effect in the presence
      of air ions the physical and biological mechanisms involved remain unclear. In
      particular, it is not clear which of several possible mechanisms of electrical
      origin (i.e. the action of the ions, the production of ozone, or the action of
      the electric field) are responsible for cell death. A study was therefore
      undertaken to clarify this issue and to determine the physical mechanisms
      associated with microbial cell death. RESULTS: In the study seven bacterial
      species (Staphylococcus aureus, Mycobacterium parafortuitum, Pseudomonas
      aeruginosa, Acinetobacter baumanii, Burkholderia cenocepacia, Bacillus subtilis
      and Serratia marcescens) were exposed to both positive and negative ions in the
      presence of air. In order to distinguish between effects arising from: (i) the
      action of the air ions; (ii) the action of the electric field, and (iii) the
      action of ozone, two interventions were made. The first intervention involved
      placing a thin mica sheet between the ionisation source and the bacteria,
      directly over the agar plates. This intervention, while leaving the electric
      field unaltered, prevented the air ions from reaching the microbial samples. In
      addition, the mica plate prevented ozone produced from reaching the bacteria. The
      second intervention involved placing an earthed wire mesh directly above the agar
      plates. This prevented both the electric field and the air ions from impacting on
      the bacteria, while allowing any ozone present to reach the agar plate. With the
      exception of Mycobacterium parafortuitum, the principal cause of cell death
      amongst the bacteria studied was exposure to ozone, with electroporation playing
      a secondary role. However in the case of Mycobacterium parafortuitum,
      electroporation resulting from exposure to the electric field appears to have
      been the principal cause of cell inactivation. CONCLUSION: The results of the
      study suggest that the bactericidal action attributed to negative air ions by
      previous researchers may have been overestimated.

PMID- 17439658
TI  - Identification of two novel glial-restricted cell populations in the embryonic
      telencephalon arising from unique origins.
AB  - BACKGROUND: Considerably less attention has been given to understanding the
      cellular components of gliogenesis in the telencephalon when compared to
      neuronogenesis, despite the necessity of normal glial cell formation for
      neurological function. Early proposals of exclusive ventral oligodendrocyte
      precursor cell (OPC) generation have been challenged recently with studies
      revealing the potential of the dorsal telencephalon to also generate
      oligodendrocytes. The identification of OPCs generated from multiple regions of
      the developing telencephalon, together with the need of the embryonic
      telencephalon to provide precursor cells for oligodendrocytes as well as
      astrocytes in ventral and dorsal areas, raises questions concerning the identity
      of the precursor cell populations capable of generating macroglial subtypes
      during multiple developmental windows and in differing locations. RESULTS: We
      have identified progenitor populations in the ventral and dorsal telencephalon
      restricted to the generation of astrocytes and oligodendrocytes. We further
      demonstrate that the dorsal glial progenitor cells can be generated de novo from
      the dorsal telencephalon and we demonstrate their capacity for in vivo production
      of both myelin-forming oligodendrocytes and astrocytes upon transplantation.
      CONCLUSION: Based on our results we offer a unifying model of telencephalic
      gliogenesis, with the generation of both oligodendrocytes and astrocytes from
      spatially separate, but functionally similar, glial restricted populations at
      different developmental times in the dorsal and ventral CNS.

PMID- 17439660
TI  - Unilateral external ophthalmoplegia in Miller Fisher syndrome: case report.
AB  - BACKGROUND: A description of the diagnostic features of Miller Fisher syndrome.
      CASE PRESENTATION: The clinical presentation, investigation, and subsequent
      progress of our patient with clinical unilateral external ophthalmoplegia.
      CONCLUSION: Our case demonstrates the presentation of clinical unilateral
      external ophthalmoplegia as part of the full triad of Miller Fisher syndrome.

PMID- 17439659
TI  - Should fine needle aspiration biopsy be the first pathological investigation in
      the diagnosis of a bone lesion? An algorithmic approach with review of
      literature.
AB  - BACKGROUND: Fine needle aspiration biopsy (FNAB) is gaining increasing popularity
      in the diagnosis of musculoskeletal lesions; and in many patients, a definitive
      diagnosis can be rendered from aspiration smears alone. Its applicability in bone
      pathology, however, has been controversial due to a high percentage of inadequate
      smears, difficulty in evaluation of tissue architecture and nonspecific results
      in the diagnosis of primary bone lesions. In this study, the value of aspiration
      as the first pathological investigation in the diagnosis of a bone lesion was
      evaluated. METHODS: 91 cases of clinically suspected cases of bone lesions were
      aspirated over a period of two years. Direct or cytospin smears were fixed in 95%
      alcohol and stained by Hematoxylin and Eosin or air-dried and later fixed in
      methanol for May Grunwald Giemsa staining. RESULTS: Of the 91 patients who were
      subjected to FNAB, 81 were considered satisfactory and 10.9 % (10) were
      inadequate?inconclusive for diagnosis. Cyto-histological concordance was obtained
      in 78.5 % (51/65) patients. Positive and negative predictive values were 87.5%
      and 97.2 % respectively. Sensitivity as a preliminary diagnostic technique was
      93.3%, whereas specificity was 94.5 %. Overall, diagnostic accuracy was 94.2 %.
      Metastatic lesions were detected with 100% accuracy. Two cases were reported as
      false positive and one case as false negative. CONCLUSION: Cytology provides
      valuable information to the clinician to make an informed decision regarding
      appropriate therapy. We conclude that time-consuming and costly investigations
      may be reduced by choosing FNAB as the initial pathological diagnostic method for
      skeletal lesions of unknown origin. The choice of radiological examinations,
      laboratory tests and surgical biopsies can be determined after the FNAB
      diagnosis.

PMID- 17439661
TI  - Short-term mortality after perforated or bleeding peptic ulcer among elderly
      patients: a population-based cohort study.
AB  - BACKGROUND: Mortality after perforated and bleeding peptic ulcer increases with
      age. Limited data exist on how the higher burden of comorbidity among elderly
      patients affects this association. We aimed to examine the association of age
      with short-term mortality after perforated and bleeding peptic ulcer and to
      determine the impact of comorbidity on this association. METHODS: In this
      population-based cohort study in three Danish counties between 1991 and 2003 we
      identified two cohorts of patients: those hospitalized with a first-time
      discharge diagnosis of perforated peptic ulcer and those with bleeding peptic
      ulcer. The diagnoses were ascertained from hospital discharge registries and
      mortality through the Danish Civil Registration System. Information on
      comorbidity and use of ulcer-related drugs was obtained through administrative
      medical databases. We computed age-, gender- and comorbidity-standardized 30-day
      mortality rates and used Cox's regression to estimate adjusted 30-day mortality
      rate ratios (MRR) for elderly compared with younger patients. RESULTS: Among
      2,061 patients with perforated peptic ulcer, 743 (36%) were 65-79 years old and
      513 patients (25%) were aged 80+ years. Standardized 30-day mortality was 8.9%
      among patients younger than 65 years rising to 44.6% among patients aged 80+
      years, corresponding to an adjusted MRR of 5.3 (95% CI: 4.0-7.0). Among 7,232
      patients with bleeding peptic ulcer 2,372 (33%) were aged 80+ years. Standardized
      30-day mortality among patients younger than 65 was 4.3% compared with 16.9%
      among patients aged 80+ years, corresponding to an adjusted MRR of 3.7 (95% CI:
      2.9-4.7). Analyses stratified by comorbidity consistently showed high MRRs among
      elderly patients, regardless of comorbidity level. CONCLUSION: Ageing is a strong
      predictor for a poor outcome after perforated and bleeding peptic ulcer
      independently of comorbidity.

PMID- 17439662
TI  - Breast cancer knowledge, attitudes, and screening behaviors among African
      American women: the Black cosmetologists promoting health program.
AB  - BACKGROUND: African American women have higher rates of breast cancer mortality
      than their white counterparts. Studies have suggested that this is partly caused
      by discovery of cancer at a later stage, highlighting the importance of
      encouraging early detection of breast cancer in this population. To guide the
      creation of a breast cancer education intervention and help focus other health
      educators' and clinicians' health promotion efforts, this study explored whether
      a cohort of African American women living in San Diego would demonstrate the
      possession of adequate baseline knowledge about breast cancer screening and
      adherence to widely recommended screening guidelines. METHODS: African American
      women (N = 1,055) from San Diego, California participated in a beauty salon-based
      survey about breast cancer knowledge, attitudes, and screening practices. Women's
      ages ranged from 20 to 94 years, with average age of 42.20 (SD = 13.53) years.
      Thirty-four percent reported completing college and/or some graduate school
      training, and 52% reported having some college or post high school formal
      training. Seventy-five percent of the sample reported working outside their home.
      Participating cosmetologists and their salons were recruited to the study through
      word-of-mouth referral by highly respected African American community leaders.
      RESULTS: Salon clients reported low rates of adherence to recommended breast
      cancer screening guidelines. Of the 1,055 participants, 31% reporting performing
      breast self-exam every month. Of those participants 40 and older, 57% reported
      having had a clinical breast exam and 43% reported having had a mammogram in the
      past year. Knowledge of breast cancer was associated with adherence to screening
      guidelines. While women recognized the serious health threat that breast cancer
      poses and that early detection of breast cancer is important, only 30% of women
      reported feeling well informed about the disease. Many participants demonstrated
      a lack of basic knowledge about breast cancer. The Health Belief Model postulates
      that access to such information is an essential element in the progression toward
      engaging in screening behaviors. CONCLUSION: Data from this study reflect a
      continuing need for increased breast cancer education for African American women.
      In light of the considerable mainstream information available related to breast
      cancer, these data reinforce the need for more breast cancer education programs
      that are clearly intended to attract the attention of African American women.

PMID- 17439663
TI  - cTFbase: a database for comparative genomics of transcription factors in
      cyanobacteria.
AB  - BACKGROUND: Comprehensive identification and classification of the transcription
      factors (TFs) in a given genome is an important aspect in understanding
      transcriptional regulatory networks of a specific organism. Cyanobacteria are an
      ancient group of gram-negative bacteria with strong variation in genome size
      ranging from about 1.6 to 9.1 Mb and little is known about their TF repertoires.
      Therefore, we constructed the cTFbase database to classify and analyze all the
      putative TFs in cyanobacterial genomes, followed by genome-wide comparative
      analysis. DESCRIPTION: In the current release, cTFbase contains 1288 putative TFs
      identified from 21 fully sequenced cyanobacterial genomes. Through its user
      friendly interactive interface, users can employ various criteria to retrieve all
      TF sequences and their detailed annotation information, including sequence
      features, domain architecture and sequence similarity against the linked
      databases. Furthermore, cTFbase provides phylogenetic trees of individual TF
      family, multiple sequence alignments of the DNA-binding domains and ortholog
      identification from any selected genomes. Comparative analysis revealed great
      variability of the TF sequences in cyanobacterial genomes. The high variance on
      the gene number and domain organization would be related to their diverse
      biological functions and their adaptation to various environmental conditions.
      CONCLUSION: cTFbase provides a centralized warehouse for comparative analysis of
      putative TFs in cyanobacterial genomes. The availability of such an extensive
      database would be of great interest for the community of researchers working on
      TFs or transcriptional regulatory networks in cyanobacteria. cTFbase can be
      freely accessible at http://cegwz.com/ and will be continuously updated when the
      newly sequenced cyanobacterial genomes are available.

PMID- 17439664
TI  - Combination of tunicamycin with anticancer drugs synergistically enhances their
      toxicity in multidrug-resistant human ovarian cystadenocarcinoma cells.
AB  - BACKGROUND: The pharmacologic modulatory effects of the antibiotic, tunicamycin
      (TM), on multidrug-resistant human UWOV2 ovarian cancer cells are reported. The
      UWOV2 cell line was derived from a cystadenocarcinoma in a patient refractory to
      combination chemotherapy with actinomycin D, vincristine (VCR), cis
      diaminedichloroplatinum (II) (CDDP) and doxorubicin (DXR). In an attempt to
      explain drug resistance in this cell line, we examined the effects of TM on their
      sensitivity to various anticancer drugs, the uptake, efflux and retention of
      [3H]VCR, and their ability to bind [14C]DXR and [3H]azidopine (AZD), a
      photoaffinity label of the multidrug transporter, P-glycoprotein (Pgp). RESULTS:
      TM effectively decreased the EC50 for DXR, EXR, VCR and CDDP, thus enhancing
      their cytotoxicity. The antibiotic also prolonged the intracellular retention
      time of [3H]VCR and increased the binding of both [14C]DXR and [3H]AZD to the
      cells. CONCLUSION: It is concluded that the pharmacomodulatory effects of TM in
      these cells are mediated by global inhibition of protein and glycoprotein
      synthesis and synergistic interaction with antineoplastic drugs. The ability of
      TM to enhance the sensitivity of drug resistant tumour cells may have impact on
      the design and optimization of novel resistance modifiers to improve the efficacy
      of combination treatment of intractable neoplasms.

PMID- 17439665
TI  - Quaternary structure of Artemia haemoglobin II: analysis of T and C polymer
      alignment and interpolymer interface.
AB  - BACKGROUND: The brine shrimp Artemia expresses four different types of
      haemoglobin subunits namely C1, C2, T1 and T2. Two of these four subunits
      dimerize in different combinations to produce the three isoforms of the
      heterodimeric Artemia haemoglobin: HbI (C1 and C2), HbII (C1 and T2) and HbIII
      (T1 and T2). Previous biochemical, biophysical and computational analyses
      demonstrate that the T and C polymers are rings of nine concatenated globin
      domains, which are covalently joined by interdomain linkers. Two such rings
      stacked coaxially give the functional molecule. This research aimed to construct
      a quaternary structural model of Artemia HbII that shows the interpolymer
      interface and domain-domain alignment, using the MS3D (mass spectrometry for
      three dimensional analysis) approach. This involved introducing chemical
      crosslinks between the two polymers, cleaving with trypsin and analyzing the
      resulting products by mass spectrometry. This was followed by computational
      analysis of the mass spectrometry data using the program SearchXlinks to identify
      putatively crosslinked peptides. RESULTS: Six putative EGS (ethylene glycol bis
      [succinimidylsuccinate]) crosslinked tryptic peptides were identified. All of
      them support a model in which the EF helices of all domains are in contact along
      the interpolymer surface, and Domain 1 of the T-polymer aligns with Domain 1 of
      the C-polymer. Any two adjacent interpolymer domain pairs contact through the
      early Helix H and early Helix A. The orientation of domains is different from the
      subunit proposed model proposed previously by this group. Crosslinking with GMBS
      (N- [gamma-maleimidobutyryloxy]succinimide ester) was also performed, and the
      results show good agreement with this model. CONCLUSION: The interpolymer EF
      contact allows the hydrophobic E and F helices to be buried in the interface and
      therefore allow the complex to solubilize readily to facilitate efficient oxygen
      transport. Furthermore the EF-contact is a common contact in cooperative
      haemoglobins and thus the model is consistent with the cooperative behaviour of
      Artemia HbII.

PMID- 17439668
TI  - Silica, silicosis and tuberculosis.
AB  - Exposure to crystalline silica dust causes multiple diseases, but silicosis and
      silica dust-associated tuberculosis (TB), in particular, are the two diseases
      that remain high on the list of occupational health priorities in low-income
      countries and that still occur in some high-income countries. The prevalence of
      silica-related TB is exacerbated by the human immunodeficiency virus (HIV)
      epidemic in low-income countries. This review describes the morphology of silica
      and the variable potency of the different forms. Sources of crystalline silica
      are discussed, with emphasis on less commonly recognised sources, such as small
      scale mining operations and agriculture. Trends in the prevalence of silicosis
      are also presented. Although efforts have been made for many years in most
      countries to reduce silica dust levels, silicosis continues to occur even in
      young people. The clinical and pathological features and diagnosis of silicosis,
      with emphasis on chest radiography, are described. The high risk of mycobacterial
      infection in silica-exposed individuals is given particular attention, with
      emphasis on control. Treatment for latent TB is recommended. The management of
      silicosis and silica-associated TB, including monitoring for early detection of
      disease and surveillance to identify disease-causing workplaces, are discussed in
      detail. Prevention of disease, in the form of dust control, remains the focus of
      the World Health Organization and International Labour Office Global Elimination
      of Silicosis Campaign. However, clinicians must be aware that silica-associated
      diseases will be around for many years to come.

PMID- 17439669
TI  - Yield of serial sputum specimen examinations in the diagnosis of pulmonary
      tuberculosis: a systematic review.
AB  - Current international tuberculosis (TB) guidelines recommend the microscopic
      examination of three sputum specimens for acid-fast bacilli in the evaluation of
      persons suspected of having pulmonary TB. We conducted a systematic review of
      studies that quantified the diagnostic yield of each of three sputum specimens.
      By searching multiple databases and sources, we identified a total of 37 eligible
      studies. The incremental yield in smear-positive results (in studies using all
      smear-positive cases as the denominator) and the increase in sensitivity (in
      studies that used all culture-positive cases as the denominator) of the third
      specimen were the main outcomes of interest. Although heterogeneity in study
      methods and results presented challenges for data synthesis, subgroup analyses
      suggest that the average incremental yield and/or the increase in sensitivity of
      examining a third specimen ranged between 2% and 5%. Reducing the recommended
      number of specimens examined from three to two (particularly to two specimens
      collected on the same day) could benefit TB control programs, and potentially
      increase case detection for several reasons. A number of operational research
      issues need to be addressed. Studies examining the most effective and efficient
      means to utilize current technologies for microscopic examination of sputum would
      be most useful if they followed an internationally coordinated and standardized
      approach, both to strengthen the country-specific evidence base and to permit
      comparison among studies.

PMID- 17439670
TI  - Introducing brief advice in tuberculosis services.
AB  - There are individual and contextual barriers to the adoption of new routines in
      health care. Health professionals working in tuberculosis (TB) care are unlikely
      to adopt smoking cessation interventions unless they understand the importance of
      such interventions, feel that doing them will produce results and are convinced
      that the interventions should be used. Health professionals need to know what
      they are expected to do and to feel they have the skills or tools necessary. But
      beyond informed, willing and ready health care providers, the health care service
      also needs to provide an encouraging infrastructure. Tobacco cessation has to be
      included in standard practice guidelines on TB case management, and information
      about smoking should be included in the standard monitoring process, with
      appropriate forms. Programme managers and technical advisors need to ask about,
      encourage and support the inclusion of smoking cessation interventions. It is
      advisable for one staff member to coordinate tobacco cessation activities to
      ensure that needed materials are available and to provide assistance and feedback
      to other staff.

PMID- 17439666
TI  - Growth control of the eukaryote cell: a systems biology study in yeast.
AB  - BACKGROUND: Cell growth underlies many key cellular and developmental processes,
      yet a limited number of studies have been carried out on cell-growth regulation.
      Comprehensive studies at the transcriptional, proteomic and metabolic levels
      under defined controlled conditions are currently lacking. RESULTS: Metabolic
      control analysis is being exploited in a systems biology study of the eukaryotic
      cell. Using chemostat culture, we have measured the impact of changes in flux
      (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of
      the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear
      growth-rate-associated trends and discriminates between carbon-sufficient and
      carbon-limited conditions. Genes consistently and significantly upregulated with
      increasing growth rate are frequently essential and encode evolutionarily
      conserved proteins of known function that participate in many protein-protein
      interactions. In contrast, more unknown, and fewer essential, genes are
      downregulated with increasing growth rate; their protein products rarely interact
      with one another. A large proportion of yeast genes under positive growth-rate
      control share orthologs with other eukaryotes, including humans. Significantly,
      transcription of genes encoding components of the TOR complex (a major controller
      of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover,
      integrative studies reveal the extent and importance of post-transcriptional
      control, patterns of control of metabolic fluxes at the level of enzyme
      synthesis, and the relevance of specific enzymatic reactions in the control of
      metabolic fluxes during cell growth. CONCLUSION: This work constitutes a first
      comprehensive systems biology study on growth-rate control in the eukaryotic
      cell. The results have direct implications for advanced studies on cell growth,
      in vivo regulation of metabolic fluxes for comprehensive metabolic engineering,
      and for the design of genome-scale systems biology models of the eukaryotic cell.

PMID- 17439671
TI  - Edward Livingston Trudeau and the outdoor life.

PMID- 17439672
TI  - Determinants of chronic obstructive pulmonary disease in Chinese patients in Hong
      Kong.
AB  - BACKGROUND: The prevalence of chronic obstructive pulmonary disease (COPD) is
      rising in many parts of the world. This is a study of risk factors for COPD in
      Chinese patients in Hong Kong. DESIGN: Case-control study matched by sex and age
      (+/-5 years). METHODS: A total of 289 consecutive patients with COPD were
      recruited from out-patient clinics while healthy controls were recruited from two
      sources: random population and community centres for senior citizens. All
      patients and controls underwent a questionnaire-based interview and spirometry.
      RESULTS: The mean ages of COPD patients and controls were 71.1 +/- 9.4 and 67.5
      +/- 9.3 years, respectively. The male to female ratio of COPD patients was 5 to
      1. Smoking was found to be the most important determinant for COPD, followed by
      poor education and low body mass index adjusted for confounders. A dose-dependent
      relationship was found between the risk of COPD and pack-years smoked. Place of
      birth, exposure to environmental tobacco smoke and a history of asthma and
      tuberculosis were not associated with increased risk of COPD. CONCLUSION: Despite
      a progressive reduction in prevalence, smoking remains the most important
      predictor of COPD in Hong Kong. Greater anti-smoking efforts are warranted.

PMID- 17439673
TI  - Polymorphisms of glutathione S-transferase genes and functional activity in
      smokers with or without COPD.
AB  - OBJECTIVE: To determine the role of polymorphisms of genes regulating glutathione
      S-transferase (GST) and its plasma GST activity in the pathogenesis of chronic
      obstructive pulmonary disease (COPD). DESIGN: Case-control study. METHODS: One
      hundred and sixty-three patients with stable COPD from several community or
      regional hospitals were matched for age and pack-years smoked with the same
      number of health controls from the general population. Each participant underwent
      an interview-based respiratory and smoking questionnaire, lung function testing
      and gave a blood sample. Genotyping was carried out using a polymerase chain
      reaction-based method for polymorphisms of glutathione S-transferase theta 1
      (GSTT1), glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase P 1
      (GSTP1) genes. Plasma GST activity was measured using the spectrofluorometric
      method. RESULTS: There were no significant differences in the distribution of
      various genotypes of polymorphisms of GSTT1, GSTM1 and GSTP1 between COPD
      patients and healthy controls. GST activity was significantly higher in patients
      compared with controls, irrespective of their different genotypes, and was not
      different between patients with different levels of airflow obstruction.
      CONCLUSION: Polymorphisms of GSTT1, GSTM1 and GSTP1 genes are unlikely to be
      involved in the pathogenesis of COPD in Chinese in Hong Kong and Southern China.

PMID- 17439674
TI  - Cerebral cortical dysfunction in chronic obstructive pulmonary disease: role of
      transcranial magnetic stimulation.
AB  - SETTING: Chest and Neurology Departments, Assiut and Al-Azhar University
      Hospitals, Egypt. OBJECTIVES: To study a large population with respect to
      previous preliminary data, using transcranial magnetic stimulation (TMS) as a
      prognostic method for evaluation of cerebral cortical functions during acute
      exacerbation of chronic obstructive pulmonary disease (AE-COPD). DESIGN: In a
      case-control study, 41 patients with AE-COPD and 30 healthy controls were
      included. For all, TMS was used to assess corticospinal pathway function and
      cortical excitability. RESULTS: Patients demonstrated increased motor threshold
      (resting and active), central motor conduction time and increased cortical silent
      period. Significant correlation was identified between TMS parameters and
      pulmonary function tests (forced vital capacity, forced expiratory volume 1%,
      forced expiratory volume in one second) and arterial blood gases (pH, paO(2) and
      HCO(3)), serum chloride and potassium. CONCLUSION: These results indicate that
      the motor cortex is less excitable during AE-COPD. This is attributed to
      reduction of cortical excitability due to chronic hypoxaemia. Therefore, early
      detection of cerebral changes might be in accordance with the importance of early
      O(2) therapy in reducing morbidity and mechanical ventilation dependency in COPD.
      This opens discussion for future early therapeutic use of GABAergic and
      glutaminergic modulating drugs with oxygen to protect the brains of COPD
      patients.

PMID- 17439675
TI  - Effects of a generalised ban on smoking in bars and restaurants, Italy.
AB  - CONTEXT: Italy implemented a law in January 2005 banning smoking in all enclosed
      public spaces. OBJECTIVES: To document perceived obstacles and effects of the law
      and observed client smoking behaviours in bars and restaurants. DESIGN: Four
      surveys were conducted between December 2004 and February 2006. Protocols and
      questionnaires were posted on a public health website to solicit participation
      among local health units (LHUs). Participating LHUs randomly selected 50 bars and
      restaurants using the electronic Yellow Pages. Self-administered questionnaires
      were delivered to owners or managers of selected locales; all of them were
      revisited during peak hours to collect questionnaires and observe client smoking.
      RESULTS: Before the ban, smokers were observed in 31% of locales; 24% of owners
      predicted major financial losses. One year later, no smokers were observed and
      only 7% reported major financial losses. Only 30% had received law enforcement
      visits. Most owners/managers (88%) reported positive attitudes about the law and
      79% reported such attitudes among clients. CONCLUSIONS: The Italian smoking law
      has drastically reduced smoking in bars and restaurants despite minimal
      enforcement visits. Perceived negative effects on profits appear limited, and the
      owners and managers and their clients are satisfied.

PMID- 17439676
TI  - Cryptococcal pneumonia in African miners at autopsy.
AB  - SETTING: Deceased miners from South Africa whose cardiorespiratory organs were
      submitted for autopsy for compensation for occupational lung diseases from 1996
      to 2000. OBJECTIVES: To 1) calculate the prevalence of cryptococcal pneumonia in
      8421 autopsied miners, a population with a high prevalence of human
      immunodeficiency virus (HIV) infection; 2) document the association of
      cryptococcal pneumonia with other pulmonary infection; 3) document the
      association of cryptococcal pneumonia with a clinical diagnosis of cryptococcal
      meningitis; and 4) determine the accuracy of the clinical diagnosis of
      cryptococcal pneumonia. DESIGN: Case series of 589 black miners with histological
      evidence of cryptococcal pneumonia at autopsy, defined as the presence of
      cryptococcal organisms in the lung parenchyma, identified by staining of the
      mucinous capsule. RESULTS: The incidence of cryptococcal pneumonia at autopsy was
      7%. Ninety-seven of the 589 cases (16.5%) had a concomitant respiratory
      infection, most commonly Pneumocystis jirovecii pneumonia (51.5%), followed by
      mycobacterial infection (42.3%). In life, cryptococcal meningitis was diagnosed
      in 46.9% and cryptococcal pneumonia in only 2.7%. CONCLUSION: Although
      tuberculosis remains the most common HIV-associated respiratory disease in
      Africa, it is important to consider the diagnosis of cryptococcal pneumonia in
      acquired immune-deficiency syndrome (AIDS) patients, and to bear in mind the
      possibility of dual pathology.

PMID- 17439677
TI  - Outcomes of HIV-infected children with tuberculosis who are started on
      antiretroviral therapy in Malawi.
AB  - SETTING: Mzuzu Central Hospital, in the northern region of Malawi, which provides
      free antiretroviral therapy (ART) to human immunodeficiency virus (HIV) infected
      adults and children, including those with tuberculosis (TB). OBJECTIVES: To
      compare outcomes in HIV-infected children who have been started on ART because of
      1) active TB, 2) a past history of TB in the last 2 years and 3) a non-TB
      diagnosis. DESIGN: Retrospective data collection using ART patient master cards
      and ART patient registers. RESULTS: Between July 2004 and September 2006, 439
      (11%) children of a total 3908 patients were started on ART. There were 29 with
      active TB, 56 with a past history of TB in the last 2 years and 354 with a non-TB
      diagnosis. The three groups were similar in nutritional indices and CD4
      lymphocyte percentages. The 6-month probability of survival was 0.86 in the
      active TB group, 0.94 in the past history of TB group and 0.89 in the non-TB
      group. 12-month survival probability for the same groups was 0.86, 0.86 and 0.88,
      respectively. CONCLUSION: HIV-infected children with active and previous TB who
      are started on ART have good outcomes that are similar to those of children
      started on ART due to a non-TB diagnosis.

PMID- 17439678
TI  - Identifying barriers to effective tuberculosis control in Senegal: an
      anthropological approach.
AB  - SETTING: Low tuberculosis (TB) cure rates (average 53%) and high treatment
      default rates (average 28%) were reported in Senegal between 1999 and 2001.
      OBJECTIVE: To qualitatively evaluate the ability of TB patients to access and
      complete treatment in Senegal, with a view to helping to develop suitable
      strategies to improve TB control. METHODS: Anthropological study conducted in a
      series of public and private, urban and rural health facilities in 2001 and 2002.
      The qualitative methods used included semi-structured and in-depth interviews of
      health staff, patients and relatives, focus group discussions, and observations
      carried in health facilities. RESULTS: Problems were identified at several levels
      of health care. The main impediments to successful patient outcomes identified
      were: limited access to TB diagnosis and treatment facilities, poor communication
      between health personnel and patients, poor quality information provided to
      patients, poorly applied directly observed treatment, lack of a strategy to trace
      defaulting patients and limited supervision of the treatment units by the
      district leadership team. CONCLUSION: The anthropological analysis of patient
      care is an appropriate means of addressing complex public health problems in
      disease control and identifying solutions that are acceptable, sustainable and
      adapted to the local context.

PMID- 17439679
TI  - Community DOT for tuberculosis in a Brazilian favela: comparison with a clinic
      model.
AB  - SETTING: Rio de Janeiro City, Brazil. OBJECTIVE: To compare community-based
      directly observed treatment (DOT) for tuberculosis (TB), using community health
      workers (CHWs), with clinic-based DOT. DESIGN: In a longitudinal study in a
      cohort of TB patients in a region of Rio de Janeiro city, we evaluated treatment
      modalities and outcomes in 1811 patients diagnosed with TB between 1 January 2003
      and 30 December 2004. Patients were offered DOT when they presented to out
      patient clinics for an initial diagnosis. DOT was provided in the clinic or in
      the community, using CHWs, for patients living in a large favela. Outcomes of
      treatment were assessed using treatment registry databases. RESULTS: Of the 1811
      TB patients, 1215 (67%) were treated under DOT; among these, 726 (60%) received
      clinic-based treatment and 489 (40%) community-based treatment. Patients offered
      community-based treatment were more likely to accept DOT (99%) than those offered
      clinic-based treatment (60%, P<0.001). Treatment success rates for new smear
      positive and retreatment TB cases were significantly higher among those treated
      with community-based DOT compared to clinic-based DOT. CONCLUSION: We conclude
      that using CHWs to deliver DOT in the community may improve TB treatment outcomes
      in selected areas such as urban slums.

PMID- 17439680
TI  - Pulmonary tuberculosis in an indigenous community in the mountains of Ecuador.
AB  - SETTING: An aboriginal community of 653 persons. OBJECTIVE: To determine the
      prevalence of pulmonary tuberculosis (PTB) and to analyse related factors.
      DESIGN: The total population was surveyed; those with chronic productive cough
      were asked to provide sputum specimens. PTB was diagnosed by bacilloscopy (acid
      fast bacilli [AFB]). An analysis of socio-economic factors and clinical history
      associated with chronic cough or positive smear for PTB was carried out using
      multiple correspondence analysis and logistic regression models. RESULTS: Two
      hundred and two patients were identified with chronic cough and 173 with chronic
      productive cough. Chronic cough was associated with having a history of PTB
      (adjusted OR=4.89, 95%CI 2.6-9.4) and with work-related migratory movements
      (adjusted OR=2.05, 95%CI 1.3-3.3). Of 92 coughers with sputum samples analysed,
      44 (47.8%) were PTB-positive, giving a prevalence of 6.7% in the whole
      population. In the groups aged 15-34 and >or=45 years, women had higher
      positivity rates than men, whereas in the group aged 35-44 years rates were
      higher in men. Twenty-seven per cent of families had one to four smear-positive
      members. CONCLUSION: The Tuberculosis Control Programme in the area studied needs
      to be strengthened, taking into account the ethnic context, work-related
      migration and the socio-economic and geographic context.

PMID- 17439681
TI  - A prevalence survey for smear-positive tuberculosis in Thai prisons.
AB  - SETTINGS: Twenty-seven prisons in Thailand. OBJECTIVES: To measure the prevalence
      of smear-positive tuberculosis (TB) and to compare its detection using the World
      Health Organization (WHO) guidelines for prisons or the International Standards
      for Tuberculosis Care (ISTC) criteria. METHOD: Prisoners who were not on TB
      medications and who had not been treated for TB in the previous 6 months were
      enrolled in the survey. Prison nurses conducted a one-time mass screening using
      the WHO questionnaire, with follow-up sputum collection in TB suspects. RESULTS:
      Of 71594 prisoners, 22132 (30.9%) were identified as TB suspects, and 254 were
      confirmed by sputum smear, for a prevalence of 354.8/100000. Males were most
      likely to be diagnosed with TB disease (OR 2.6), as were those transferring in
      from another prison versus new prisoners (OR 3.0). The positive predictive value
      of the WHO criteria was 1.2%, and that of the ISTC standard was 5.9%. CONCLUSION:
      TB prevalence in this survey remained high. WHO guidelines, recognised as a
      standard, require health workers to question prisoners and measure height and
      weight. The ISTC standard, a single question about cough >or=2 weeks, is simple,
      may be asked by non-health personnel and may be a better alternative.

PMID- 17439682
TI  - A survey of tuberculosis prevalence in Hanoi, Vietnam.
AB  - OBJECTIVE: To assess the prevalence of tuberculosis (TB) in Hanoi, Vietnam, in
      2003/2004. METHODS: A random selection was carried out involving 11624 subjects
      from 20 communes within the city. RESULTS: On chest X-ray examination, 317
      subjects (2.73%) showed abnormal lung opacity, of which 17 were sputum smear
      positive, two concentrated smear-positive and three culture-positive, all with
      active TB. The prevalence of sputum smear-positive pulmonary TB was 146 per
      100000 in persons aged >or=15 years (95%CI 65-228). CONCLUSION: This is the first
      large-scale assessment of the prevalence of TB in Hanoi. The prevalence rate was
      higher than expected, suggesting that a significant number of patients with
      active TB, particularly females, remain undiagnosed, thus representing a
      continuing potential source of transmission in the community.

PMID- 17439683
TI  - Steep increases in tuberculosis notification among young men in the
      industrialised districts of Danang, Vietnam.
AB  - BACKGROUND: Tuberculosis (TB) notification is increasing among young adults in
      urban provinces in Vietnam, despite having achieved World Health Organization
      targets for treatment success and case detection. OBJECTIVES: To identify causes
      for non-declining TB case rates in an urban area of Vietnam, and to describe
      trends in new smear-positive pulmonary TB notification by age, sex and district
      in the period 1999-2004 in Danang City, Vietnam. RESULTS: Age and sex
      standardised notification rates declined by 1.3% (95%CI -2.3-0.3%) annually.
      Notification rates among men aged 15-44 in Danang City increased significantly
      (5%, 95%CI 2.4-7.7 annually), most notably in industrialised districts (>or=12%
      annually). CONCLUSION: TB notification rates among young men in an urban setting
      in Vietnam increased most notably in industrialised districts. We hypothesise
      that this is due to poor living and working conditions and internal migration
      rather than to an emerging human immunodeficiency virus epidemic.

PMID- 17439684
TI  - Trend of anti-tuberculosis drug resistance in Korea, 1994-2004.
AB  - SETTING: The 245 health centres through which the National Tuberculosis Programme
      (NTP) is implemented in Korea and the TB Laboratory Network of the Korean
      National Tuberculosis Association. OBJECTIVE: To observe the trend of anti
      tuberculosis drug resistance in Korea from 1994 to 2004 and possible related
      factors. DESIGN: All tuberculosis (TB) patients registered for treatment at the
      health centres for a given period were assessed. RESULTS: Of 2636 new smear
      positive patients from the 2004 survey, 338 cases (12.8%, 95% confidence interval
      [CI] 11.5-14.1) showed resistance to any of the first-line drugs: 261 with
      isoniazid (INH) resistance (9.9%, 95%CI 8.8-11.0) and 71 with multidrug
      resistance (MDR) (2.7%, 95%CI 2.1-3.3). Compared with previous surveys, a
      statistically significant increase in MDR (P=0.00675), any drug resistance
      (P=0.03779), any INH resistance (P=0.00313) and any rifampicin resistance (P =
      0.00176) has been observed among new cases since 1994. Any resistance to second
      line drugs ranged from 0.1% (capreomycin) to 1.1% (para-aminosalicylic acid)
      among new cases and from 1.1% to 3.6% among retreatment cases. Resistance to
      kanamycin and ofloxacin was found in 1.4% and 2.6%, respectively, of new and
      previously treated MDR-TB cases. CONCLUSION: A statistically significant increase
      in drug resistance was noticed among new cases.

PMID- 17439685
TI  - Tuberculosis in non-UK-born persons, England and Wales, 2001-2003.
AB  - SETTING: England and Wales, 2001-2003. OBJECTIVES: To describe demographic and
      clinical characteristics of tuberculosis (TB) in non-UK-born persons and compare
      with UK-born cases to inform public health action and health service provision.
      DESIGN: Analysis of surveillance data. RESULTS: Among the 67% of cases who were
      non-UK-born, TB incidence was 88/100000 compared to 4/100000 among the UK-born.
      UK-born minority ethnic groups were also at increased risk of TB. Although the
      highest TB incidence occurred in recent entrants to the UK, nearly half the cases
      had been resident for >or=5 years. The majority of non-UK-born cases originated
      from South Asia (48%) and sub-Saharan Africa (35%). The demographic
      characteristics of non-UK-born and UK-born cases differed. In addition, non-UK
      born cases were less likely to have pulmonary TB than the UK-born (52% vs. 73%,
      chi(2) P<0.001), but were more likely to have isoniazid-resistant disease (8% vs.
      6%, chi(2) P=0.002), depending on region of birth. CONCLUSIONS: During 2001-2003,
      most TB cases were non-UK-born. TB services need to take the characteristics of
      TB in this group into account. Furthermore, awareness of the risk of disease is
      required among the non-UK-born for many years after arrival into the UK, and
      among UK-born minority ethnic groups.

PMID- 17439686
TI  - Treatment outcome cohort analysis in an integrated DOTS and DOTS-Plus TB program
      in Latvia.
AB  - International guidelines for treatment outcome analysis of tuberculosis cases
      have been published and are widely used. They do not, however, fully address the
      incorporation of multidrug-resistant tuberculosis (MDR-TB) cases. Here we present
      an approach to cohort analysis of treatment outcomes for all registered TB cases,
      including MDR-TB cases. We analyzed all new pulmonary smear- and/or culture
      positive cases registered in Latvia during 2002. Analysis of treatment outcomes
      at 24 months after initial case registration showed overall treatment success at
      84%. This approach to outcome analysis is possible only for settings where MDR-TB
      treatment is established.

PMID- 17439687
TI  - Improving the quality of cohort analysis by incorporating treatment outcomes of
      'transferred in' TB cases.
AB  - Treatment outcomes of patients with tuberculosis (TB) who move between TB units
      ('transferred out') are often not incorporated in the annual cohort analysis.
      Experience from Morocco shows that using a simple method, the outcomes of these
      patients, notified as 'transferred in' cases, can be easily taken into account
      when compiling the annual report on treatment outcomes. With this method the
      treatment success rate increased in Morocco by a median of 5.8% (range 5.0-6.7),
      indicating that the country reached the global target of curing at least 85% of
      the new smear-positive TB cases detected during the period 1995-2003.

PMID- 17439688
TI  - [Inequalities in health and socioeconomics: an epidemiological undertaking in an
      urban area of Argentina].
AB  - OBJECTIVES: To understand how certain socioeconomic factors interact with health
      indicators at the local level, so that health inequalities may be better
      addressed. METHODS: Several epidemiological methods were applied to study the 431
      census block groups of the Lanus municipality in the province of Buenos Aires,
      Argentina, from January 1995 to December 2002. Using a cluster study, the block
      groups were categorized according to demographic and socioeconomic traits. A
      spatial distribution analysis was conducted of each health-related event in terms
      of its geographic location (georeference), and comparisons were drawn using box
      plot charting for each group. Four types of demographic and socioeconomic data
      were gathered from the 1991 National Population and Housing Census: housing
      adequacy, overcrowding, percentage of persons 65 and older in the household, and
      level of education. The health indicators studied were vaccination coverage among
      children entering primary school, teen pregnancy rates, and breast cancer
      mortality rates in women over 40 years old. RESULTS: Teen pregnancy rates fell as
      socioeconomic conditions improved (chi(2) = 60.7452; P = 4.074 x 10(-13)). In
      contrast, the breast cancer mortality rate among women over 40 was higher among
      those with a better standard of living (chi(2) = 12.9766; P = 0.0047). Although
      the average number of children with incomplete vaccination schedules at school
      entry decreased with improved socioeconomic conditions, the difference was not
      statistically significant (chi(2) = 6.3993; P = 0.0937). CONCLUSIONS: The
      combined methodologies confirmed the correlation between socioeconomic factors
      and health indicators, especially regarding teen pregnancy and breast cancer
      mortality rates. The results should be extremely helpful in designing
      interventions aimed at reducing health inequalities at the local level.

PMID- 17439689
TI  - Health-related behaviors and overweight: a study of Latino adolescents in the
      United States of America.
AB  - OBJECTIVES: This study examined, by gender, differences in being overweight among
      adolescents of Mexican, Puerto Rican, and other Latin American heritage who live
      in the United States of America, and investigated the relationships between these
      differences and socioeconomic status, health-related behaviors, and family
      characteristics. METHODS: This cross-sectional survey study obtained and analyzed
      data from nationally representative samples of Latino 8th and 10th graders in the
      Monitoring the Future study from 1991 to 2004 (N = 11 265). RESULTS: A higher
      proportion of Mexican-American girls were overweight than other Latin American
      girls, both before and after adjusting for many confounders. For both genders,
      being overweight was inversely associated with socioeconomic status and frequency
      of vigorous exercise, and positively associated with the amount of television
      viewing. No family characteristic variable examined was associated with
      overweight. CONCLUSIONS: Time spent exercising and time spent watching television
      are two potentially modifiable risk factors that, if targeted, may result in
      important reductions in overweight. The findings indicate the need to identify
      gender- and culturally-appropriate interventions that can increase physical
      activity and reduce sedentary activities among Latino adolescents, particularly
      in families of low socioeconomic status.

PMID- 17439690
TI  - [Lessons learned from an early intervention violence prevention program in
      Medellin, Colombia].
AB  - OBJECTIVE: To describe the components and development of the Early Prevention of
      Violence Program in the city of Medellin, Colombia, and to evaluate the results
      of its first phase, three years after implementation. METHODS: A before (2001)
      and after (2004) study of four variables--direct aggression, indirect aggression,
      prosocial behavior, and scholastic achievement--was conducted among a convenience
      sample of 339 program participants and their families. RESULTS: Several program
      benefits were noted. Decreases in both direct and indirect aggression were
      observed, though the latter was reduced only in girls and in those over 12 years
      old. Prosocial behavior increased among children of all ages and both genders,
      including those who exhibited low levels of prosocial behavior in 2001. In
      addition, improved school performance was seen in the group as a whole. Results
      may have been affected by some changes to the prevention program's implementation
      and by the dangerous nature of the neighborhood, which limited the home visits.
      CONCLUSIONS: The program seems to be an effective intervention for highly
      aggressive children, among whom a decline in direct aggression was observed. It
      also offers preventive benefits, as evidenced by the rise of prosocial behaviors
      in less aggressive children.

PMID- 17439691
TI  - [The effectiveness of the oral cancer prevention and early diagnosis program in
      Sao Paulo, Brazil].
AB  - OBJECTIVE: To evaluate the results of the 2004 oral cancer prevention and early
      diagnosis program carried out in conjunction with the annual flu vaccination
      campaign for the elderly in the state of Sao Paulo, Brazil. METHODS: Data
      concerning the follow-up of patients referred for diagnostic investigation of
      soft tissue lesions identified on visual inspection were collected from the
      reports issued by the State Health Department/Oral Health Technical Center. The
      following two characteristics were evaluated as indicators of the program's
      effectiveness: (1) the number of people whose problem was resolved at the primary
      care level or in referral services and (2) the number of persons with a confirmed
      diagnosis of oral cancer. The following indicators were used to assess program
      ineffectiveness: (1) patients not appearing at the referral unit, (2) inability
      of the primary care services to resolve the problem, and (3) the absence of
      follow-up information on patients. RESULTS: In 2004, 238 087 people >/= 60 years
      old were examined, corresponding to 6.8% of the state population in this age
      group (3 494 555 people). The program was carried out in 23 of the state's 24
      health regions. However, only 8 of the regions recorded follow-up information. Of
      the 5 280 people in the 8 regions who were referred for diagnostic investigation
      of soft tissue lesions, 60.5% had their problem resolved, 0.5% (26 cases) had a
      confirmed diagnosis of oral cancer, and 22.5% did not have the diagnostic
      investigation completed. For 16.5% of the cases referred for further study, there
      was no information available concerning follow-up and outcomes. CONCLUSIONS: The
      oral cancer prevention and early diagnosis program was ineffective, given the
      lack of monitoring of results in most parts of the state of Sao Paulo, and the
      high proportion of patients whose soft tissue lesion was not resolved. The
      usefulness of continuing the program in future years needs to be evaluated.

PMID- 17439692
TI  - The role of public policies in reducing smoking prevalence and deaths: the
      Argentina Tobacco Policy Simulation Model.
AB  - OBJECTIVES: To compare tobacco control policies independently and as a package
      through a simulation model to project smoking prevalence and associated future
      premature mortality in Argentina beginning in 2001. METHODS: A simulation model
      of tobacco control policies known as SimSmoke was modified using data for
      Argentina on population, fertility and mortality, smoking prevalence, and tobacco
      control policies in effect between 2001 and 2004. We used the Argentina Tobacco
      Policy Simulation model (ATPSM) to consider the effect on smoking prevalence of
      changes in taxes and prices, clean air laws, media campaigns, cessation programs,
      and youth access policies on smoking initiation and cessation rates. Smoking
      prevalence and relative risks of smoking were used to estimate smoking
      attributable mortality. The ATPSM was used to project smoking prevalence and
      smoking-attributable deaths during the period 2001-2034. RESULTS: The largest
      reductions in smoking prevalence and premature mortality were predicted for a
      comprehensive tobacco control policy package, but relative reductions of as much
      as 30% were also predicted for large tax increases. Adding a media campaign along
      with programs to publicize and enforce clean air laws, advertising bans, and
      youth access laws would further reduce smoking rates by up to 45% by the year
      2034, and would save almost 16 000 lives per year. CONCLUSIONS: Tobacco control
      policies can substantially reduce smoking rates, which can save many lives.
      Without such policies, deaths from smoking, and associated medical costs, will
      increase. The ATPSM is expected to provide guidance in filling the most important
      information gaps pertinent to both modeling and policy-making in Argentina, e.g.,
      the lack of data on initiation and cessation rates, and the need for studies on
      the impact of policies. Similar models might be developed for other Latin
      American countries.

PMID- 17439693
TI  - [Integrated strategy for dengue prevention and control in the Region of the
      Americas].
AB  - During the last 22 years, the Region of the Americas has seen an upward trend in
      dengue incidence, with epidemics peaking ever higher and recurring every 3-5
      years, almost regularly. A major factor in the spread of the disease has been the
      diminished capacity of national programs to respond with dengue prevention and
      control. This paper evaluates the Integrated Strategy for Dengue Prevention and
      Control-approved by the 44th Directing Council of the Pan American Health
      Organization in September 2003- and its preliminary results. The Integrated
      Strategy for Dengue is a management model designed to strengthen national
      programs, with a focus on reducing morbidity, mortality, and the societal and
      economic burdens produced by outbreaks and epidemics. Currently, 11 of the
      countries in the Region have developed a plan for or implemented a national
      strategy. In addition, a sub-Regional plan has been developed for Central America
      and the Dominican Republic. The Integrated Strategy for Dengue is expected to
      produce a qualitative leap forward in prevention and control through stronger
      partnerships among the State, its various ministries, and governing bodies, at
      all levels; private companies; and the range of community and civil groups. Once
      implemented, this strategy will reduce risk factors for dengue transmission,
      establish an integrated epidemiological surveillance system, decrease Aedes
      aegypti mosquito populations, prepare laboratories to better detect and identify
      the virus, optimize diagnosis and treatment, and, as a result, decrease the
      frequency, magnitude, and severity of dengue outbreaks and epidemics.

PMID- 17439694
TI  - Hyperbaric oxygen in neurological diseases.

PMID- 17439695
TI  - Basic physiology of hyperbaric oxygen in brain.
AB  - Oxygen is the proverbial 'double-edged sword' in that it is a necessity for life
      in moderation and toxic and detrimental to life in excess. This too is the
      dilemma in hyperbaric oxygen (HBO) treatment in cerebral ischemic-anoxic insults
      such as stroke, head injury, near drowning, asphyxia, cardiac arrest, etc., i.e.
      the brain at risk, where regions of ischemia are beside regions of marked
      hyperemia. The natural heterogeneity of normal brain tissue oxygenation compounds
      the problem with different microvascular brain regions living at various levels
      of oxygenation from 0 to arterial PO(2) as an added complication. The application
      of HBO, whether normobaric or hyperbaric, will result in brain tissue oxygenation
      ranging from normoxic to highly hyperoxic with the latter possibly exacerbating
      the injury sustained. On this basis, the application of multiple therapeutic
      interventions may be considered, for example, HBO in combination with free
      radical scavengers or inhibitors of free radical generating enzymes. Despite
      these difficulties in moderating oxygen delivery to treat cerebral ischemic
      anoxic insults, overwhelming preclinical evidence indicates that HBO administered
      during or within 2 hours post-insult effectively attenuates the severity of brain
      damage sustained. The primary disconnection between pre-clinical and clinical
      efficacy of HBO then appears to be the time of application. Clinically, HBO
      therapy is applied at the earliest 6 hours post-insult but usually between 12
      hours or longer post-insult. Pre-hospital application of HBO may be required for
      clear-cut demonstration of clinical efficacy.

PMID- 17439697
TI  - Hyperbaric oxygen and cerebral physiology.
AB  - Hyperbaric oxygen (HBO) therapy is defined by the Undersea and Hyperbaric Medical
      Society (UHMS) as a treatment in which a patient intermittingly breathes 100%
      oxygen under a pressure that is greater than the pressure at sea level [a
      pressure greater than 1 atmosphere absolute (ATA)]. HBO has been shown to be a
      potent means to increase the oxygen content of blood and has been advocated for
      the treatment of various ailments, including air embolism, carbon monoxide
      poisoning, wound healing and ischemic stroke. However, definitive established
      mechanisms of action are still lacking. This has led to uncertainty among
      clinicians, who have understandingly become hesitant in regard to using HBO
      therapy, even in situations where it could prove beneficial. Therefore, this
      review will summarize the literature regarding the effects of HBO on brain
      oxygenation, cerebral blood flow and intracranial pressure in both the healthy
      and injured brains, as well as discuss how changes in these three factors can
      impart protection.

PMID- 17439696
TI  - Endothelial-neutrophil interactions during ischemia and reperfusion injury: basic
      mechanisms of hyperbaric oxygen.
AB  - Ischemia/reperfusion injury plays a central role in the development of tissue
      injury during multiple central nervous system diseases including acute stroke.
      Neutrophil adhesion to the endothelium indicates a major component of
      ischemia/reperfusion pathophysiology, and may be a target for therapeutic
      intervention. Hyperbaric oxygen has been documented to reduce
      ischemia/reperfusion injury in a number of different experimental models and in a
      single human randomized clinical trial. One mechanism responsible for the
      beneficial effect of hyperbaric oxygen in treatment of ischemia/reperfusion
      injury involves suppression of neutrophil-endothelial adhesion. This review
      intends to describe the current basic mechanisms responsible for hyperbaric
      oxygen-mediated inhibition of neutrophil-endothelial interactions following
      ischemia/reperfusion injury.

PMID- 17439698
TI  - HBO and gas embolism.
AB  - Gas embolism, which occurs with the entry of gas into the circulatory system from
      the vein, artery or both, is a potentially serious even fatal condition. The two
      main causes of gas embolism are iatrogenic and diving. The site of entry and the
      signs and symptoms distinguish between arterial and venous embolism. The entering
      gas may be air, but may also be CO(2) or other gases, especially in iatrogenic
      embolism. Supportive care is the primary therapy for venous gas embolism, while
      hyperbaric oxygen therapy in addition to supportive care is the first line of
      treatment for arterial gas embolism. In this article, we will review the
      pathophysiology, etiology, diagnosis and treatment of gas embolism.

PMID- 17439699
TI  - Hyperbaric oxygen and carbon monoxide poisoning: a critical review.
AB  - CO is likely to be the most common cause of poisoning worldwide and often results
      in persistent neuropathologic and cognitive sequelae. While the displacement of
      oxygen from hemoglobin by CO has overshadowed the myriad mechanisms by which CO
      causes injury, mere oxygen displacement has endured as the etiology of CO
      poisonings and perpetuated a cascade of misdiagnosis, misunderstandings and
      confusion regarding how and when to treat CO poisoning. Hyperbaric oxygen
      benefits the brain more than normobaric oxygen by, e.g. improving energy
      metabolism, preventing lipid peroxidation and decreasing neutrophil adherence.
      Randomized controlled trials have definitively shown hyperbaric oxygen as the
      only efficacious therapy for acute CO poisoning if delayed neurological sequelae
      are to be minimized. Normobaric oxygen should not be used between multiple
      hyperbaric oxygen treatments as this can contribute to toxicity. Hyperbaric
      oxygen seems to also have potential in the delayed treatment of CO poisoning
      using multiple treatments of low dose of oxygen; however, oxygen dosing issues
      are not yet fully understood for either acute or delayed treatment. It would
      behoove medical decision-makers to embrace this important tool and make it more
      accessible as well as helping to disseminate to the medical community what is now
      known from the available literature.

PMID- 17439700
TI  - Hyperbaric oxygenation in fluid microembolism.
AB  - Because clinicians require objectively demonstrable neurological deficits to
      confirm a diagnosis, the recognition of embolic events in the nervous system is
      generally restricted to the effects of ischemic necrosis produced by arterial
      occlusion. However, magnetic resonance imaging (MRI) has shown that lesser
      degrees of damage associated with small emboli are common, especially in the mid
      brain, and are usually clinically silent. They are frequently associated with
      atheromatous embolism in the elderly, but microembolic debris, such as fat, is
      common in the systemic venous return of healthy people and generally trapped in
      the microcirculation of the lung being removed by phagocytosis. However,
      pulmonary filtration may fail and microemboli may also pass through an atrial
      septal defect in so-called 'paradoxical' embolism. Studies of bubbles formed on
      decompression in diving have demonstrated the importance of pulmonary filtration
      in the protection of the nervous system and that filtration is size dependant, as
      small bubbles may escape entrapment. Fluid and even small solid emboli, arresting
      in or passing through the cerebral circulation, do not cause infarction, but
      disturb the blood-brain barrier inducing what has been termed the 'perivenous
      syndrome'. The nutrition of areas of the white matter of both the cerebral
      medulla and the spinal cord depends on long draining veins which have been shown
      to have surrounding capillary free zones. Because of the high oxygen extraction
      in the microcirculation of the gray matter of the central nervous system, the
      venous blood has low oxygen content. When this is reduced further by embolic
      events, tissue oxygenation may fall to critically low levels, leading to blood
      brain barrier dysfunction, inflammation, demyelination and eventually, axonal
      damage. These are the hallmarks of the early lesions of multiple sclerosis where
      MR spectroscopy has also shown the presence of lactic acid. Significant elevation
      of the venous oxygen tension requires oxygen to be provided under hyperbaric
      conditions. Arterial tension is typically increased ten-fold breathing oxygen at
      2 atmospheres absolute (ATA), but this results in only a 1.5-fold increase in the
      cerebral venous oxygen tension. The treatment of decompression sickness, and both
      animal and clinical studies, have confirmed the value of oxygen provided under
      hyperbaric conditions in the restoration and preservation of neurological
      function in the 'perivenous' syndrome.

PMID- 17439701
TI  - Hyperbaric oxygen in traumatic brain injury.
AB  - OBJECTIVES: This critical literature review examines historical and current
      investigations on the efficacy and mechanisms of hyperbaric oxygen (HBO)
      treatment in traumatic brain injury (TBI). Potential safety risks and oxygen
      toxicity, as well as HBO's future potential, are also discussed. METHODS:
      Directed literature review. RESULTS: Historically, cerebral vasoconstriction and
      increased oxygen availability were seen as the primary mechanisms of HBO in TBI.
      HBO now appears to be improving cerebral aerobic metabolism at a cellular level,
      namely, by enhancing damaged mitochondrial recovery. HBO given at the ideal
      treatment paradigm, 1.5 ATA for 60 minutes, does not appear to produce oxygen
      toxicity and is relatively safe. DISCUSSION: The use of HBO in TBI remains
      controversial. Growing evidence, however, shows that HBO may be a potential
      treatment for patients with severe brain injury. Further investigations,
      including a multicenter prospective randomized clinical trial, will be required
      to definitively define the role of HBO in severe TBI.

PMID- 17439702
TI  - A review of oxygen therapy in ischemic stroke.
AB  - Neuroprotective drugs have so far failed clinical trials, at high cost, and
      intravenous tissue plasminogen activator (i.v. tPA) remains the only FDA-approved
      acute stroke therapy. Hyperoxia, acting via multiple direct and indirect
      mechanisms, may be a powerful neuroprotective strategy to salvage acutely
      ischemic brain tissue and extend the time window for acute stroke treatment. Of
      the available oxygen delivery methods, hyperbaric oxygen therapy (HBO) appears to
      be the most potent, while even normobaric oxygen therapy (NBO) may be effective
      if started promptly after stroke onset. HBO has so far failed to show efficacy in
      three clinical trials. The failure of these trials is probably attributable to
      factors such as delayed time to therapy, inadequate sample size and use of
      excessive chamber pressures. Previous trials did not assess long-term benefit in
      patients with tissue reperfusion. In this modern era of stroke thrombolysis and
      advanced neuroimaging, oxygen therapy may have renewed significance. If applied
      within the first few hours after stroke onset or in patients with imaging
      evidence of salvageable brain tissue, oxygen therapy could be used to 'buy time'
      for the administration of thrombolytic or neuroprotective drugs. This article
      reviews the history and current rationale for using oxygen therapy in stroke, the
      mechanisms of action of HBO and the results of animal and human studies of
      hyperoxia in cerebrovascular diseases.

PMID- 17439703
TI  - Hyperbaric oxygenation in peripheral nerve repair and regeneration.
AB  - Peripheral nerves are essential connections between the central nervous system
      and muscles, autonomic structures and sensory organs. Their injury is one of the
      major causes for severe and longstanding impairment in limb function. Acute
      peripheral nerve lesion has an important inflammatory component and is considered
      as ischemia-reperfusion (IR) injury. Surgical repair has been the standard of
      care in peripheral nerve lesion. It has reached optimal technical development but
      the end results still remain unpredictable and complete functional recovery is
      rare. Nevertheless, nerve repair is not primarily a mechanical problem and
      microsurgery is not the only key to success. Lately, there have been efforts to
      develop alternatives to nerve graft. Work has been carried out in basal lamina
      scaffolds, biologic and non-biologic structures in combination with neurotrophic
      factors and/or Schwann cells, tissues, immunosuppressive agents, growth factors,
      cell transplantation, principles of artificial sensory function, gene technology,
      gangliosides, implantation of microchips, hormones, electromagnetic fields and
      hyperbaric oxygenation (HBO). HBO appears to be a beneficial adjunctive treatment
      for surgical repair in the acute peripheral nerve lesion, when used at lower
      pressures and in a timely fashion (<6 hours).

PMID- 17439704
TI  - Hippocampal Nogo-A and neo-Timm's staining in amygdala kindling rats.
AB  - PURPOSE: Nogo-A, one of the axon regeneration inhibitors, has been shown to be up
      regulated in both the experimental and human temporal lobe epilepsy. However, the
      role of Nogo-A in mossy fiber sprouting (MFS) relative to epileptogenesis is
      unknown. This work was designed to examine the relationship of the hippocampal
      Nogo-A protein expression with MFS during the development of amygdala kindling.
      METHODS: Using immunohistochemistry and neo-Timm's histological procedures, we
      evaluated the distribution and density of Nogo-A and Nogo-66 receptor (Ng-R)
      expression and MFS in the bilateral hippocampus of amygdala kindling rats.
      RESULTS: Nogo-A expression in the ipsilateral hippocampus gradually increased
      with the development of kindling in the sector CA2-3. In contrast, no increased
      Nogo-A expression was observed in the contralateral hippocampus as the rats
      advanced to stage 5 kindled seizures. Furthermore, poorer Nogo-A and Nogo-66
      receptor (Ng-R) expression were observed in the dentate granule cells as aberrant
      MFS occurred. CONCLUSIONS: In amygdala kindling rats, generalized stage 5
      seizures were not associated with increased Nogo-A expression in the
      contralateral hippocampus supporting the concept that seizures by themselves do
      not induce Nogo-A expression. Furthermore, in the ipsilateral hippocampus, the
      expression of Nogo-A relative to MSF suggests that this protein may partially
      control aberrant synaptic reorganization during epileptogenesis.

PMID- 17439705
TI  - Increased number and differentiation of neural precursor cells in the brainstem
      of superoxide dismutase 1(G93A) (G1H) transgenic mouse model of amyotrophic
      lateral sclerosis.
AB  - The superoxide dismutase 1(G93A G1H) (SOD1(G93A G1H)) transgenic mouse is a model
      of familial human amyotrophic lateral sclerosis (ALS) that has progressive
      neurodegeneration within the spinal cord and brainstem. In this study, we
      investigated the number and differentiation of neural precursor cells (NPCs).
      Nestin-positive NPCs were rarely seen in the nervous system of wild type controls
      or pre-disease mice at post-natal days 30 and 60. With disease onset on post
      natal day 90, nestin labeled NPCs proliferated preferentially in the brainstem
      with maximal number and density at post-natal day 120. NPCs did not double-label
      with CNPase or O(4) markers of oligodendrocytes. The majority of the NPCs co
      labeled with the astrocyte maker glial fibrillary acidic protein (GFAP) and a
      small number with the neuronal marker NeuN. At disease onset, 73 and 10% of NPCs
      co-expressed GFAP and NeuN respectively while at severe disease stage, 80 and 8%
      of the NPCs co-expressed GFAP and NeuN. Proliferating cell nuclear antigen (PCNA)
      was used to confirm that at least some of these cells undergo mitosis. Future
      studies could be directed at controlling the differentiation of these endogenous
      NPCs into neurons and astrocytes in order to ameliorate the degeneration within
      the brainstem of the ALS mouse.

PMID- 17439706
TI  - Doppler ultrasound measurement of blood flow volume in the extracranial internal
      carotid artery for evaluation of brain perfusion after aneurysmal subarachnoid
      hemorrhage.
AB  - Monitoring of cerebral blood flow (CBF) is an essential part in the early
      diagnosis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage
      (SAH). Several methods have been established to monitor cerebral perfusion in
      these patients. During last few years, a new sonographic approach has been
      introduced, the so called 'angle independent ultrasound system' for monitoring
      volume flow in the internal carotid artery (ICA). The angle independent Doppler
      ultrasound system Quantix ND (Cardiosonix Ltd, Israel) determines the diameter of
      the ICA as well as the velocity of blood flow in the extracranial part of this
      vessel. Thus, a determination of the global CBF in the anterior circulation can
      be achieved. Aim of our study was to compare the Quantix ND system and the
      commonly used transcranial Doppler sonography (TCD) in patients suffering from
      aneurysmal SAH. We included 11 patients (eight female and three male; Hunt and
      Hess I-V) and performed post-operatively/post-interventionally daily measurement
      of blood flow volume in the ICA, and determined the blood flow velocity in middle
      and anterior cerebral artery (MCA and ACA) with TCD. Six patients post
      operatively/post-interventionally developed cerebral vasospasm, resulting in
      ischemia and territorial infarction. Three patients were chosen as case studies.
      In contrast to the TCD, we found a strong significant correlation of blood flow
      volume with Quantix ND in the ICA and the occurrence of cerebral infarction
      (p<0.001). These preliminary data justify further investigation of this angle
      independent Doppler ultrasound device. We postulate that this new tool might be
      effective for monitoring the CBF in the critical post-operative/post
      interventional interval following aneurysmal SAH.

PMID- 17439707
TI  - Thalamic hypometabolism on 18FDG-positron emission tomography in medial temporal
      lobe epilepsy.
AB  - OBJECTIVES: Degree of hypometabolism in the thalamus on (18)Fluorodeoxyglucose
      positron emission tomography (FDG-PET) was compared with those of medial and
      lateral temporal lobes in patients with medial temporal lobe epilepsy (mTLE), and
      its relationship with post-operative seizure outcomes was investigated. METHODS:
      Twenty-six patients with mTLE who underwent anterior temporal lobectomy were
      included. Post-operatively, 13 patients became completely seizure-free and 13
      showed residual seizure, regardless of frequency (five patients became almost
      seizure-free, six had rare seizures and two showed significant improvements).
      Degrees of hypometabolism in bilateral thalamus, ipsilateral medial and lateral
      temporal lobes were evaluated visually and semi-quantitatively by determining the
      asymmetry index (AI), a value indicating 100 x (ipsilateral - contralateral)/[1/2
      x (ipsilateral + contralateral)] and the region-to-cerebral hemisphere ratio (R/C
      ratio) being the ratio between averaged counts in each area and those in the
      cerebral hemisphere of the same side. RESULTS: Hypometabolism in the medial
      temporal lobe was visually observed in all patients. Hypometabolism in the
      lateral temporal lobe was observed in 20 patients and was semi-quantitatively
      more prominent than that of the medial temporal lobe. Pathologically, hippocampal
      sclerosis and prominent astrogliosis of the lateral temporal lobe were present in
      all cases. However, while thalamic hypometabolism was visually observed in nine
      patients (in the ipsilateral side of four cases, contralateral side of three and
      on both sides of two), no significant thalamic hypometabolism was semi
      quantitatively observed. No significant differences in metabolic rate in any area
      except for the lateral temporal lobe between seizure-free patients and residual
      seizure patients were seen semi-quantitatively. DISCUSSION: Data indicated that
      metabolism in the lateral temporal lobe of patients with mTLE significantly
      decreased and revealed pathologic glial changes. Thalamic hypometabolism was
      quite mild and did not correlate with post-operative seizure outcome.

PMID- 17439708
TI  - Providing timely dental treatment for young children under general anesthesia is
      a government priority.

PMID- 17439709
TI  - Antibiotic prophylaxis practices in dentistry: a survey of dentists and
      physicians.
AB  - BACKGROUND: A survey was conducted to determine prescribing practices of general
      dental and medical practitioners regarding the use of antibiotics for
      prophylaxis. MATERIALS AND METHODS: A questionnaire with an accompanying letter
      was designed to investigate prescribing practices of general dentists and
      physicians. The survey encompassed demographic data, mechanisms to keep current
      with prophylactic practice, first- and second-line drugs prescribed with doses
      and directions, applicable medical conditions and dental procedures warranting
      antibiotic prophylaxis. Names were chosen randomly from provincial lists and
      ethics approval was granted. Responses were compared with 1997 American Heart
      Association (AHA) guidelines. RESULTS: In all, 1,500 surveys were sent to each
      group, with a response rate of 32% of dentists and 17% of physicians. There was a
      significant difference (p < 0.05) between dentists (95%) and physicians (71%) in
      selecting the correct first-line antibiotic, amoxicillin, and in choosing the
      correct dose of amoxicillin (i.e., 2 g, 1 hour before treatment): 88% of dentists
      and 48% of physicians (p < 0.05). Appropriate second-line drugs were correctly
      selected by 84% of dentists and 67% of physicians--a significant difference (p <
      0.05)--with clindamycin chosen most often (82% and 49%, respectively). Over 90%
      of respondents in both professions correctly identified conditions, such as
      prosthetic heart valve and endocarditis, requiring antibiotic prophylaxis.
      CONCLUSIONS: Clinicians are not always aware of current clinical guidelines, and
      dentists and physicians exhibit different patterns regarding antibiotic
      prescribing. Dentists are more familiar than physicians with current protocols of
      the AHA.

PMID- 17439710
TI  - From clinician to researcher--a first-hand account.
AB  - While teaching and clinical care may be somewhat intuitive, research is much less
      so, and a lack of research experience or opportunity to do research can be
      frustrating to the faculty member who is trying to become well-rounded. In an
      effort to ease the transition from clinical teacher to clinical researcher, the
      faculty of dentistry at Dalhousie University has developed a research mentorship
      program. The purpose of this paper is to report on the opportunities and
      challenges that 2 dental clinicians experienced when they participated in the
      pilot phase of an epidemiologic survey of the oral health status of seniors. In
      their academic role, these 2 clinical examiners, who were full-time faculty
      members, concentrated on classroom and clinical teaching. Although neither had
      previous clinical research experience, both were interested in broadening their
      horizons by engaging in research in the hope of attaining a variety of positive
      outcomes.

PMID- 17439711
TI  - Efficacy of new LED light-curing units in hardening of Class II composite
      restorations.
AB  - PURPOSE: The aim of this study was to determine the efficacy of new light
      emitting diode (LED) curing units in the hardening of Class II composite
      restorations. METHODS AND MATERIALS: Disk specimens 2 mm in diameter and 2.5 mm
      thick were prepared from 2 composites (Vit-l-escence, shade A3, Ultradent;
      Herculite XRV, shade A2, Kerr) in the following manner. An extracted permanent
      molar tooth was prepared to receive a Class II restoration with proximal slot
      only. The tooth was sectioned horizontally on a plane above the gingival floor
      level such that the remaining depth of the proximal box was 4 mm. A Tofflemire
      matrix band and retainer were secured around the tooth. Composite specimens were
      placed below the tooth to coincide with the location of the slot opening at the
      bottom of the gingival floor. The specimens were subjected to light
      polymerization with various combinations of curing cycle and light unit: 1 of 3
      continuous curing cycles (20 seconds, 40 seconds or 60 seconds) and 1 of 2 LED
      units (Utralume-5, Ultradent; IQ Smartlite, Dentsply) or a control quartz
      tungsten-halogen (QTH) unit (Optilux 501, Kerr). Specimens were stored at 37
      degrees C for 24 hours. A hardness tester was used to obtain 4 measurements of
      Knoop hardness number (KHN) for each surface (upper and lower) of each specimen.
      Relative hardness (RH) was calculated as the KHN of the lower surface divided by
      the KHN of the upper surface. Data were analyzed with analysis of variance
      (ANOVA) and Tukey"s test. RESULTS: ANOVA indicated significant differences in
      mean RH among the groups (p < 0.001). RH increased with increasing curing time.
      For the 60-second cycle with Vit-l-escence composite, mean RH was 0.47, 0.25 and
      0.39 for the Ultralume-5, IQ Smartlite and Optilux 501 curing units,
      respectively. For the 60-second cycle with Herculite XRV composite, mean RH was
      0.71, 0.81 and 0.56 for the Ultralume-5, IQ Smartlite and Optilux 501 curing
      units, respectively. CONCLUSIONS: In general, the 2 LED units performed as well
      as the QTH unit; however, brand of composite and curing cycle had significant
      effects on RH values.

PMID- 17439712
TI  - Microleakage of Class II posterior composite restorations with gingival margins
      placed entirely within dentin.
AB  - PURPOSE: Composite restorations are more frequently being placed with margins
      apical to the cementoenamel junction. However, margins within dentin are prone to
      microleakage. The purpose of this in vitro study was to evaluate various
      restorative procedures in terms of their ability to reduce microleakage in
      posterior composite restorations with gingival margins within dentin. We also
      examined the effect of staining time on microleakage. MATERIALS AND METHODS:
      Mesio-occlusal and disto-occlusal preparations were made in 50 extracted molars.
      Teeth were randomly assigned to receive 1 of 5 treatments followed by restoration
      with Z100 composite resin: acid etch (control); Clearfil SE Bond; Prompt-L-Pop;
      Vitrebond/Scotchbond Multipurpose Plus (closed-sandwich technique); or
      Geristore/Tenure (open-sandwich technique). After 48 hours of water storage
      followed by sectioning buccolingually, 1 restoration from each tooth was randomly
      assigned to either 2- or 4-hour immersion in 50% by weight silver nitrate
      solution. Restorations were removed and gingival floors analyzed to determine the
      percentage of surface area stained in each of 3 0.5-mm wide zones. RESULTS:
      Repeated measures ANOVA did not reveal statistically significant differences in
      staining for 2 and 4 hours. Compared with the control group, Clearfil SE bond
      produced statistically significant reductions in leakage in all 3 zones. Prompt-L
      Pop did not reduce leakage significantly except in zone 3 (closest to the pulp).
      Vitrebond and Geristore both reduced microleakage in zones 2 and 3, but the
      reduction was greater with the use of Vitrebond. CONCLUSION: Both Clearfil SE
      Bond and Vitrebond in a closed-sandwich technique were effective methods for
      reducing microleakage within dentin.

PMID- 17439713
TI  - Oral and maxillofacial side effects of radiation therapy on children.
AB  - Radiation therapy of the head and neck frequently results in serious and
      sometimes unavoidable changes to orofacial structures, particularly for children.
      Acute and chronic complications have a great impact on their oral function and
      quality of life. This paper provides an overview of the side effects of radiation
      therapy on children's oral and dental tissues, and highlights appropriate
      preventive guidelines and management strategies to minimize these complications.

PMID- 17439714
TI  - Clinical limitations of Invisalign.
AB  - Adult patients seeking orthodontic treatment are increasingly motivated by
      esthetic considerations. The majority of these patients reject wearing labial
      fixed appliances and are looking instead to more esthetic treatment options,
      including lingual orthodontics and Invisalign appliances. Since Align Technology
      introduced the Invisalign appliance in 1999 in an extensive public campaign, the
      appliance has gained tremendous attention from adult patients and dental
      professionals. The transparency of the Invisalign appliance enhances its esthetic
      appeal for those adult patients who are averse to wearing conventional labial
      fixed orthodontic appliances. Although guidelines about the types of
      malocclusions that this technique can treat exist, few clinical studies have
      assessed the effectiveness of the appliance. A few recent studies have outlined
      some of the limitations associated with this technique that clinicians should
      recognize early before choosing treatment options.

PMID- 17439715
TI  - JNK pathway: diseases and therapeutic potential.
AB  - c-Jun N-terminal protein kinases (JNK), also known as stress-activated protein
      kinases, were originally identified by their ability to phosphorylate the N
      terminal of the transcription factor c-Jun and by their activation in response to
      a variety of stresses. JNK are multifunctional kinases involved in many
      physiological processes. The JNK pathway has been shown to play a major role in
      apoptosis in many cell death paradigms and its association with a variety of
      pathological processes is gradually been recognized. This review will concentrate
      on describing the involvement of the JNK pathway in the context of different
      diseases and the potential to adopt the JNK pathway components as therapeutic
      targets.

PMID- 17439716
TI  - Magnesium lithospermate B possesses inhibitory activity on Na+,K+-ATPase and
      neuroprotective effects against ischemic stroke.
AB  - AIM: To examine if magnesium lithospermate B (MLB) extracted from Danshen, the
      dried roots of Salvia miltiorrhiza, may act as an active component responsible
      for the cardiac therapeutic effect of this traditional Chinese herb via the same
      molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin.
      Moreover, we wanted to test if MLB may provide neuroprotection against ischemic
      stroke as observed for cardiac glycosides. METHODS: Similarity in the chemical
      structure and molecular configuration between MLB and ouabain was analyzed. The
      inhibition potency of MLB and ouabain on Na( +),K( +) -ATPase activity of a
      commercial product, as well as in purified membrane fractions from rat brain and
      heart tissues, was examined and compared. Neuroprotective effect of MLB against
      ischemic stroke was also evaluated using a cortical brain slice-based assay
      model. RESULTS: Dose-dependent inhibition on the commercial Na( +),K( +)-ATPase
      equivalent to that for ouabain was observed for MLB of approximately half dosage
      by weight. This relative potency of ouabain and MLB was also observed for their
      inhibition on Na( +),K( +)-ATPase activity of plasma membrane purified from rat
      tissues, although these 2 inhibitors exhibited somewhat lower competence in these
      crude extracts. In ischemic gerbil brains, post-treatment with MLB significantly
      reduced the infarct size, visualized by 2,3,5-triphenyltetrazolium chloride
      staining, by approximately 55% when compared with the control group. CONCLUSION:
      These results evidently suggest that the cardiac therapeutic effect of Danshen
      should be at least partly attributed to the effective inhibition of Na( +),K( +)
      ATPase by MLB, and that MLB provides anti-ischemic neuroprotection in gerbils
      subjected to focal ischemia and reperfusion.

PMID- 17439717
TI  - A cell-based model of alpha-synucleinopathy for screening compounds with
      therapeutic potential of Parkinson's disease.
AB  - AIM: To develop a cell-based model by stable transfection of SH-SY5Y with mutant
      A53T human alpha-synuclein, recapitulating neurotoxicity of alpha -synuclein
      overexpression. METHODS: The overexpression of mutant alpha -synuclein was
      analyzed by Western blotting, immunocytochemistry, and RT-PCR. Cell viability was
      processed when treated with different concentrations of 1-methyl-4
      phenylpyridinium (MPP+) and exogenous dopamine (DA) for 24, 48, and 72 h by 3
      (4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Early
      apoptosis and late apoptosis/necrosis were analyzed by flow cytometry using
      Annexin V and propidium iodide double staining, respectively. DNA was isolated
      and applied to agarose gel for electrophoresis; the typical DNA
      "ladder"represented severe apoptosis. We also used this model to screen 99
      compounds with therapeutic potential by MTT assay. RESULTS: One of the stably
      transfected clones overexpressed exogenous genes on both the protein level and
      the transcriptive level. Significant differences in cytotoxicity were found
      between the pcDNA3.1(+) group and the pcDNA3.1(+)-hm alpha-synuclein group in the
      presence of the same concentration of MPP+ and DA within the same incubation
      time. The level of either early apoptosis or late apoptosis/necrosis was
      remarkably increased in transfected cells compared with the control after
      treatment with 100 micromol/L MPP+ for 24 h. In addition, the presence of the
      typical DNA "ladder" was observed in the pcDNA3.1(+)-hm alpha-synuclein group
      when treated with 200 micromol/L MPP+ for 48 h. After the screening experiment,
      12 of the 99 compounds were found to decrease DA-induced cytotoxicity on cell
      viability. CONCLUSION: We established a cell-based model which is useful for
      studying the function of alpha-synuclein and screening compounds with therapeutic
      potential. In addition, it was identified that cells overexpressing A53T mutant
      alpha-synuclein were significantly vulnerable against MPP+ or dopamine exposures.

PMID- 17439718
TI  - l-Stepholidine increases the frequency of sEPSC via the activation of D1 dopamine
      signaling pathway in rat prelimbic cortical neurons.
AB  - AIM: To investigate the effect of l-stepholidine (SPD) on the frequency of
      spontaneous excitatory postsynaptic currents (sEPSC) in the pyramidal cells
      between layers V and VI in the prelimbic cortex (PL). METHODS: A whole-cell patch
      clamp in rat brain slices was used. RESULTS: SPD significantly increased the
      frequency of sEPSC in a concentration-dependent manner. A selective D1 dopamine
      receptor antagonist SCH23390 blocked SPD-mediated effects, whereas the D1 agonist
      SKF38393, but not the D2/3 antagonist sulpiride, mimicked SPD-mediated increase
      in the frequency of sEPSC. Moreover, both protein kinase A (PKA) inhibitor N-(2-
      [p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide hydrochloride and protein
      kinase C (PKC) inhibitor chelerythrine attenuated the effect of SPD on sEPSC.
      CONCLUSION: SPD elicits its effect on the frequency of sEPSC on the PL pyramidal
      cells via presynaptic D1 receptors, and is dependent on PKA and PKC signaling
      pathways.

PMID- 17439719
TI  - Time-dependence of cardiomyocyte differentiation disturbed by peroxisome
      proliferator-activated receptor alpha inhibitor GW6471 in murine embryonic stem
      cells in vitro.
AB  - AIM: To investigate the possible roles of peroxisome proliferator-activated
      receptor alpha(PPAR alpha) and the signal pathway regulating the transcription of
      PPAR alpha in the cardiomyocyte differentiation course of murine embryonic stem
      (ES) cells in vitro. METHODS: The expression of PPAR alpha during cardiomyocyte
      differentiation was analyzed using both Western blotting and immunofluorescence.
      Cardiac specific genes and sarcomeric proteins were evaluated when embryoid
      bodies were challenged with PPAR alpha specific inhibitor GW6471 at different
      time courses. The phosphorylation of p38 mitogen-activated protein kinase (MAPK)
      was studied in the differentiation process, and its specific inhibitor SB203580
      was employed to study the function of p38 MAPK on cardiac differentiation and the
      expression of PPAR alpha. RESULTS: The expression of PPAR alpha was observed to
      be at a low level in undifferentiated ES cells and markedly induced with the
      appearance of beating clusters. The inhibition of PPAR alpha by its specific
      inhibitor GW6471 (1X10(-5) mol/L) significantly prevented cardiomyocyte
      differentiation and resulted in the reduced expression of cardiac sarcomeric
      proteins (ie alpha-actinin, troponin-T) and specific genes (ie alpha-MHC, MLC2v)
      in a time-dependent manner. In the differentiation course, p-p38 MAPK was
      maintained at a high level from d 3 followed by a decrease from d 10. The
      inhibition of the p38 MAPK pathway by SB203580 between d 3 and d 7 efficiently
      prevented cardiomyocyte differentiation and resulted in the capture of the
      upregulation of PPAR alpha. CONCLUSION: Taken together, these results showed a
      close association between PPAR alpha and cardiomyocyte differentiation in vitro,
      and p38 MAPK was partly responsible for the regulation of PPAR alpha.

PMID- 17439720
TI  - Hypertonic and isotonic potassium solutions have different effects on vessel
      contractility resulting in differences in optimal resting tension in rat aorta.
AB  - AIM: To compare high K(+ )-induced contraction and optimal resting tension
      measured by two commonly used techniques of hypertonic and isotonic K(+ ) in
      aortas with and without adventitial fat from various age rats. METHODS: Three age
      groups of rats (15, 25, and 62 weeks) were used to prepare thoracic aortic rings
      in which adventitial fat was either removed or left intact. High K(+ ) (30
      mmol/L)-induced contractions were observed under increasing resting tensions of
      1.0, 1.5, 2.0, 2.5, 3.0, and 3.5 g. Optimal resting tension was the resting
      tension at which the aorta showed a maximal contraction. RESULTS: The
      contractions induced by 2 kinds of high K(+ ) were significantly different.
      Hypertonic and isotonic K(+ ) induced a different style of contraction, and the
      pattern varied with different ages. At the age of 15 weeks, isotonic K(+ )
      induced contractions were greater than hypertonic K+-induced contractions.
      However, at the age of 62 weeks, isotonic K(+ )-induced contractions were smaller
      than hypertonic K(+ )-induced contractions. Optimal resting tensions measured by
      2 kinds of high K(+ ) were inconsistent. Optimal resting tensions in different
      kinds of aortic preparations from various age rats were almost a constant of 2 g,
      determined by isotonic K(+ ), but a variable, determined by hypertonic K(+ ). The
      adventitial fat could delay the development of high K(+ )-induced contractions at
      different resting tensions, but had little effect on the maximal contractions.
      CONCLUSION: Hypertonic and isotonic K(+ ) may produce different contractions
      resulting in differences in optimal resting tension in rat aorta.

PMID- 17439721
TI  - Prenatal exposure to lipopolysaccharide results in increases in blood pressure
      and body weight in rats.
AB  - AIM: To investigate the effects of prenatal exposure to lipopolysaccharide (LPS)
      on blood pressure and body weight of offspring in rats. METHODS: Sixteen healthy,
      pregnant rats were randomly divided into 2 groups. The rats in the LPS group were
      injected intraperitoneally with LPS (0.79 mg/kg) on the d 8, d 10, and d 12 of
      gestation. Those in the control group were only treated with normal saline. After
      delivery, all offspring were weighed and blood pressure was measured by the
      tailcuff method once every 2 weeks from the 6th to the 24th week. In the 15th
      week, their food intake was weighed every day. At the end of the 24th week, the
      rats were killed by decapitation. Abdominal adipose tissues were weighed, and the
      serum level of leptin was detected by radioimmunoassay. RESULTS: The offspring
      with prenatal LPS exposure showed increased systemic arterial pressure, heavier
      body weight, elevated food intake, increased adipose tissue weight, and increased
      circulating leptin compared with the controls. CONCLUSION: Prenatal exposure to
      LPS leads to increases in blood pressure and body weight in rats.

PMID- 17439722
TI  - Co-application of ricin A chain and a recombinant adenovirus expressing ricin B
      chain as a novel approach for cancer therapy.
AB  - AIM: To develop a novel ricin-based approach for the safe and effective therapy
      of cancer. METHODS: The ricin A chain (RTA) was expressed in Escherichia coli in
      the form of a 6XHis-tagged fusion protein and purified with Ni(2+)-NTA affinity
      resin. A replication-deficient ricin B chain (RTB)-expression adenovirus green
      fluorescence protein (AdGFP-RTB) was constructed. RTA and AdGFP-RTB were tested
      for cytotoxicity either individually or in combination in human cell lines
      HEK293, HeLa, SMMC7721, and HL7702. Cell viability was determined with trypan
      blue staining or MTT assay. RESULTS: The expression and release of RTB, as well
      as the entry of RTA into AdGFP-RTB-infected cells were confirmed. When RTA and
      AdGFP-RTB was used individually, neither was toxic to the cells. When they were
      applied together, significant cell death was observed in all of the cell lines
      tested. The cell-killing effect correlated with the amount of RTA protein used,
      with cell mortality at about 60% at 4.8 mu g RTA in combination with AdGFP-RTB at
      100 pfu/cell. No major cell killing was seen when RTA was used in combination
      with a control adenovirus AdGFP. The treatment of healthy HeLa cells with the
      virusfree supernatant from AdGFP-RTB/RTA-treated HeLa cells resulted in cell
      death, suggesting the formation of RTA/RTB complex, and a potential by-stander
      effect. CONCLUSION: The new approach was successful in vitro. Further
      modifications of the adenovirus vector, as well as an in vivo study are needed to
      confirm its potential in cancer therapy.

PMID- 17439723
TI  - Neocartilage formation from predifferentiated human adipose derived stem cells in
      vivo.
AB  - AIM: To examine the chondrogenic potential of human adipose derived stem cells
      (hASC) induced by human transforming growth factor beta2 (hTGF beta2) in vitro,
      and to investigate if predifferentiated hASC can produce neocartilage in vivo.
      METHODS: hASC were isolated from subcutaneous adipose tissue and cultured in
      pellets with the addition of hTGF beta2. Chondrogenic differentiation was assayed
      by RT-PCR, Western blotting, toluidine blue staining, and immunohistochemistry
      staining for collagen type II. For the in vivo study, intact induced cell pellets
      or the released cells embedded in alginate gel with different concentrations were
      implanted subcutaneously in nude mice. Specimens were harvested at different time
      points and carried with histological and immunohistochemistry examination to
      evaluate the cartilage formation. RESULTS: RT-PCR analysis revealed that hASC
      produced aggrecan and collagen type II after 7 d of induction and continued
      throughout the culture period. This was also demonstrated by the Western blot
      analysis, positive staining of toluidine blue, and immunohistochemistry for
      collagen type II. After reseeding in the monolayer, the cells isolated from the
      pellets displayed a polygonal morphology compared with the primary spindle shape.
      hASC were released from the induced cell pellets when embedded in alginate gel
      (implanted cell concentration=5X10(6) /mL or higher). They produced neocartilage
      after 12 weeks in vivo culture; however, intact induced cell pellets implanted
      subcutaneously rapidly lost their differentiated phenotype. CONCLUSION:
      Chondrogenesis of hASC in vitro can be induced by combining pellet culture and
      hTGF beta2 treatment. Predifferentiated hASC embedded in alginate gel have the
      ability of producing neocartilage in vivo.

PMID- 17439724
TI  - Nitrofen suppresses cell proliferation and promotes mitochondria-mediated
      apoptosis in type II pneumocytes.
AB  - AIM: To characterize the molecular mechanisms of nitrofen-induced pulmonary
      hypoplasia. METHODS: After administration of nitrofen to cultured type II A549
      pneumocytes, cell proliferation and DNA synthesis were investigated by 3-(4,5-
      dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide colorimetry, colony
      formation assay, flow cytometry and [3H]-thymidine incorporation assay. Apoptosis
      was measured by terminal transferase-mediated dUTP nick-end-labeling, acridine
      orange-ethidium bromide staining and flow cytometry. Expression of proliferating
      cell nuclear antigen (PCNA) and apoptosis-related genes was assayed by
      immunofluorescence, RT-PCR and Western blot. RESULTS: Nitrofen inhibited the cell
      proliferation of A549 cells in a dose- and time-dependent manner, accompanied by
      downregulation of PCNA. As a result, the DNA synthesis of nitrofentreated A549
      cells decreased, while cell cycle was arrested at G0/G1 phase. Moreover, nitrofen
      induced apoptosis of A549 cells, which was not abolished by Z-Val-Ala- Asp(OCH3)-
      fluoromethylketone. In addition, nitrofen decreased the expression of Bcl-x( L),
      but not of Bcl-2, Bax, and Bak, resulting in a loss of mitochondrial membrane
      potential and the nuclear translocation of apoptosis-inducing factor (AIF).
      Meanwhile, nitrofen strongly activated the p38 mitogen-activated protein kinase
      (p38-MAPK). Pretreatment of cells with SB203580 (5 micromol/L) blocked nitrofen
      induced phosphorylation of p38-MAPK and abolished nitrofen-induced AIF
      translocation and apoptosis in A549 cells. CONCLUSION: Nitrofen suppresses the
      proliferation of cultured type II pneumocytes accompanied by the downregulation
      of PCNA, and induces mitochondria-mediated apoptosis involving the activation of
      p38-MAPK.

PMID- 17439725
TI  - Effects of gestrinone on uterine leiomyoma and expression of c-Src in a guinea
      pig model.
AB  - AIM: To investigate the effect of gestrinone on uterine leiomyomas and the
      expression of c-Src, estradiol receptors (ER), and progesterone receptors (PR) in
      a guinea pig model. METHODS: After being oophorectomized, the guinea pigs were
      allocated into random groups. The model group was treated with estradiol benzoate
      (E2) for 16 weeks. In the gestrinone-treated groups, the animals were treated
      with E2 for 6 weeks in advance, and then in combination with gestrinone for 10
      weeks. Histological examination was performed to evaluate whether there were
      leiomyoma features in the animals. The protein levels of c-Src, phospho-(
      416)Src, ER, and PR were assayed by Western blotting and an immunohistochemical
      method. RESULTS: Morphological changes were observed in the myometrium of the
      guinea pig model, including an increase of uterine weights, proliferation of
      uterine smooth muscles, and the formation of nodules. High protein levels of c
      Src, phospho- 416Src, ER, and PR were observed in the myometrium of the guinea
      pig model. In the gestrinone-treated group, there were no nodules observed. The
      histological features of the myometrium were similar to that of the control
      group. Low protein levels of c-Src, phospho-(416 )Src, ER, and PR were observed
      in the gestrinonetreated group. CONCLUSION: The upregulation of c-Src and phospho
      (416 )Src indicated that the activity of c-Src is augmented in the uterine
      leiomyoma model. c-Src was associated with the formation of uterine leiomyomas in
      the model, and gestrinone markedly suppressed the growth of uterine leiomyomas in
      the model. Gestrinone inhibited not only the protein expression of ER and PR, but
      also c-Src and the autophosphorylation of c-Src in the guinea pig leiomyoma
      model.

PMID- 17439726
TI  - Cytotoxic T lymphocyte response induced by an improved synthetic lipopeptide
      vaccine against cervical cancer.
AB  - AIM: To explore cytotoxic T lymphocyte (CTL) response induced by the lipopeptide
      vaccine against cervical cancer. METHODS: The immunological effect inducing CD8+
      T cell-mediated cytotoxicity was investigated in human leukocyte antigen (HLA)-A2
      transgenic mice and peripheral blood mononuclear cells (PBMC) of healthy HLA
      A2.1+blood donor. The activity of specific CTL was measured by using a standard 4
      h( 51)Cr release assay. The content of major histocompatibility complex (MHC) I
      on T2 cells and the expression of immune molecules on dendritic cells (DC) were
      detected by flow cytometry, and the concentrations of interleukin (IL)-12 and
      interferon-gamma were determined by ELISA. RESULTS: The lipopeptide induced a
      strong epitope-specific CTL response both in vivo (transgenic mice) and in vitro
      (human PBMC). This CTL induction was critically dependent on the presence of the
      helper T lymphocyte epitope in transgenic mice, and the presence of a lipid tail
      bypassed the need for an adjuvant. The stability and persistence of the antigenic
      complex formed with the lipopeptide increased in comparison with the CTL parental
      peptide. The lipopeptide could induce the production of IL-12 in DC, but not the
      maturation of DC directly. CONCLUSION: The combination of CTL and the T helper
      epitope and lipid molecule can remarkably improve the immunogenicity of the CTL
      peptide, the mechanism of which is associated with an increase in the stability
      and persistence of the antigenic complex formed with the lipopeptide and in the
      production of IL-12 in DC induced by the lipopeptide. The lipopeptide can be
      considered a more effective vaccine type for human being.

PMID- 17439727
TI  - Effects of notoginosides on proliferation and upregulation of GR nuclear
      transcription factor in hematopoietic cells.
AB  - AIM: To investigate the effects of panax notoginosides (PNS) on the proliferation
      of human hematopoietic stem/progenitor cells, and to explore the signaling
      pathway of the nuclear transcription factor of the glucocorticoid receptor (GR
      NTF) initiated by PNS related with the proliferation. METHODS: The human CD34+
      cells and bone marrow nuclear cells were exposed to PNS at a concentration of 0,
      10, 25, 50, and 100 mg/L, respectively, in semi-solid culture system to observe
      colony forming unite of all lineages, granulocyte, erythrocyte, and megakaryocyte
      (CFUGEMM, CFU-GM, CFU-E, and CFU-MK). Three lineages of human hematopoietic cell
      lines, including granulocytic HL-60, erythrocytic K562, megakaryocytic CHRF- 288,
      and Meg-01 cells were incubated with PNS at 20 mg/L for 14 d. Meanwhile,
      dexamethasone (Dex) was used as a positive control. The nuclear protein of the
      cells was analyzed by Western blotting with monoclonal antibodies against the
      amino or carboxyl terminus of GR-NTF. Electrophoretic mobility shift assay
      performed by using the 32P-radiolabeled GR-NTF consensus oligonucleotide.
      RESULTS: PNS promoted the proliferation of CD34+ cells and significantly raised
      the colony numbers of CFU-GEMM by 34.7%+/-16.0% over the non-PNS control
      (P<0.01). PNS also enhanced the proliferation of CFU-GM, CFU-E, and CFU-MK by
      39.3%+/- 5.7%, 33.3%+/-7.3%, and 26.2%+/-3.2%, respectively. GR-NTF protein
      levels of either the amino or carboxyl terminus in K562, CHRF-288, and Meg-01
      treated by PNS increased by 2.4-2.8 fold and 1.3- 3.9 fold over the untreated
      cells. GR-NTF binding activity, initiated by either PNS or Dex, was apparently
      elevated to form the complex of GR-NTF with DNA as higher density bands in K562
      and CHRF-288 cells, and some activity appeared as a band in HL-60 cells induced
      by PNS. CONCLUSION: PNS displayed the action of hematopoietic growth factor-like
      or synergistic efficacy to promote proliferation of human progenitor cells, may
      play a role in the upregulation of gene expression related to proliferation of
      hematopoietic cells through increasing the GR-NTF synthesis and its DNA binding
      activity.

PMID- 17439728
TI  - Bufalin induces apoptosis in human osteosarcoma U-2OS and U-2OS methotrexate300
      resistant cell lines.
AB  - AIM: To investigate the antiproliferative activity and apoptosis-inducing effects
      of bufalin on human osteosarcoma cell lines. METHODS: U-2OS and U-2OS
      methotrexate (MTX) 300-resistant cell lines were treated with bufalin. Cell
      viability was assessed using the MTT assay. Cell-cycle status, apoptosis-inducing
      effects, and the expression of apoptosis-related proteins were evaluated by flow
      cytometry, fluorescent staining, DNA fragmentation assays, and Western blotting.
      The effect of bufalin on dihydrofolate reductase (DHFR) expression was studied by
      RTPCR and Western blotting. RESULTS: Bufalin inhibited cell growth in both U-2OS
      and U-2OS MTX300 cells. The induction of G2/M cell-cycle arrest was also seen in
      the cells treated with bufalin. The induction of apoptosis by bufalin was
      confirmed by increased expression of the tumor suppressor protein p53 and the
      increased ratio of the Bax/Bcl-2 proteins. Bufalin induced apoptosis to the same
      extent in both cell lines without regard to DHFR levels in the cells. CONCLUSION:
      Bufalin inhibited the growth of and induced apoptosis in both MTX-sensitive and
      MTX-resistant human osteosarcoma U-2OS cells. The apoptosis-inducing effect of
      bufalin was not influenced by the presence of high levels of the DHFR protein.

PMID- 17439729
TI  - Pretreatment with insulin enhances anticancer functions of 5-fluorouracil in
      human esophageal and colonic cancer cells.
AB  - AIM: To investigate the effects of insulin on enhancing 5-fluorouracil (5-FU)
      anticancer functions and its mechanisms in the human esophageal cancer cell line
      (Eca 109) and human colonic cancer cell line (Ls-174-t). METHODS: The effect of
      insulin/5-FU combination treatment on the growth of Eca 109 and Ls-174-t cells
      was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide
      (MTT) assay. After insulin treatment or insulin/5-FU treatment, cell cycle
      distribution of both cell lines was analyzed by flow cytometry. Western blot
      assay was used to assess the expression of caspase-3 and thymidylate synthase
      (TS). Apoptosis was detected by flow cytometry, DNA fragmentation assay, and
      terminal transferase dUTP nick end labeling assay (TUNEL). Moreover, the changes
      of 5-FU uptake after insulin pretreatment were detected by HPLC assay and Western
      blot analysis. RESULTS: We found that insulin enhanced the inhibitory effect of 5
      FU on cell proliferation when Eca 109 cells and Ls-174-t cells were pretreated
      with insulin for the appropriate time. Insulin increased the cell number of the S
      phase and the uptake of 5-FU. Insulin/5-FU treatment enhanced apoptosis of tumor
      cells and upregulated the expression of cleaved caspase-3 compared with 5-FU
      treatment. Moreover, insulin/5-FU treatment induced the changes of free TS and
      the TS ternary complex level compared with 5-FU treatment in Eca 109 and Ls-174-t
      cells. CONCLUSION: These data suggest that insulin enhances anticancer functions
      of 5- FU when it is treated before 5-FU for the appropriate time in human
      esophageal and colonic cancer cell lines.

PMID- 17439730
TI  - Affinity of anticancer drug, daunomycin, to core histones in solution: comparison
      of free and cross-linked proteins.
AB  - AIM: The interaction of anthracycline anticancer drugs with chromatin,
      nucleosomes and histone H1 has been extensively studied. In the present study,
      for the first time, we have investigated the binding of anthracycline antibiotic,
      daunomycin, to free and cross-linked thymus core histones (CL-core) in solution
      and in the absence of DNA. METHODS: Fluorescence, UV/Vis spectroscopy and
      equilibrium dialysis techniques were used. RESULTS: The UV spectroscopy results
      show that daunomycin induces hypochromicity in the absorption spectra of the core
      histones. Fluorescence emission intensity is decreased upon daunomycin binding
      and the process is concentration dependent. The equilibrium dialysis shows that
      the binding is positive cooperative with the binding sites as Scatchard plot and
      Hill Coefficient confirm it. CONCLUSION: The results suggest that daunomycin
      shows much higher affinity to core histones free in solution than to CL-core,
      implying that the binding is most likely due to the accessibility of these
      proteins to the environment. It is suggested that daunomycin binds strongly to
      open state of histones, such as in tumor cells, rather than to their compact
      structure seen in normal chromatin.

PMID- 17439731
TI  - Pharmacokinetic-pharmacodynamic modeling of telmisartan using an indirect
      response model in spontaneously hypertensive rats.
AB  - AIM: To investigate the pharmacokinetic (PK) and the pharmacodynamic (PD)
      properties of telmisartan in spontaneously hypertensive (SH) rats using an
      indirect response and effect-compartment link models, and compare two PK-PD
      models fitting quality. METHODS: The SH rats received a single oral dose of 2, 4,
      and 8 mg/kg of telmisartan. The plasma concentrations of telmisartan were
      determined by the liquid chromatography-mass spectrum method. The mean arterial
      blood pressure was measured to characterize the pharmacodynamics of telmisartan
      by tail-cuff manometry. The relationship for the telmisartan concentration
      hypotensive effect in the SH rats was characterized using an indirect response
      model. RESULTS: The PK parameters showed dose proportionality, with a long
      terminal half-life of 16 h, a clearance of 0.15 Lxkg( -1) xh( -1), and a volume
      of distribution of 5.36 Lxkg( -1) in the study. For the indirect response PD
      model, the estimated K(in) were 36.6, 34.1, and 32.8 %.h( -1), K(out) were 36.7,
      34.6, and 31.9 h( -1); the IC(50) values were 86.2, 95.8, and 91.1 ngxmL( -1);
      and the area under the effect curve (AUEC) were 762.8, 1490.5, and 2086.2 mmHg.h
      at three doses, respectively. For the effect-compartment model, the K(eo) were
      29.4, 33.8, and 28.7 h( -1); the IC(50) values were 78.2, 85.7, and 80.9 ngxmL(
      1), and the AUEC were 781.5, 1602.8, and 2215.7 mmHg.h at three doses,
      respectively. CONCLUSION: According to Akaike's information criterion values, the
      proposed indirect response model provided a more appropriate and good-fitting
      PK/PD characterization of telmisartan than the effect-compartment link model in
      SH rats.

PMID- 17439732
TI  - Artificial pulmonary surfactant as a carrier for intratracheally instilled
      insulin.
AB  - AIM: The relative bioavailabilities and effects on lung injury alleviation of 4
      insulin- artificial pulmonary surfactant (INS-APS) preparations were studied in
      normal rats. The relationship between the minimal surface tension (Gamma(min ))
      of INS-APS and the absorption of insulin was also investigated. METHODS: Four
      formulations of APS [1,2-dipalmitoyl-sn-glycero-3-phosphocholine
      (DPPC)/lecithin/palmitic acid (PA), DPPC/1-hexadecanol (Hex)/tyloxapol (Tyl),
      DPPC/L-alpha-phosphatidyl-DL-glycerol sodium salt (PG), DPPC/Tyl] were prepared
      by thin-film sonication method and direct sonication. The Gamma(min ) of 4 APS
      dispersions was examined with and without INS by pulsating with a bubble surface
      tensiometer. In vivo experiments were performed in which serum glucose change and
      the insulin level were measured by an enzymatic glucose reagent kit and a
      radioimmunology assay kit after IT to rats. The reduction in lung injury by INS
      APS following 7 d of consecutive administration was evaluated by the pulmonary
      edema index (the weight ratio of wet lung to dry lung) and histopathology
      examination. RESULTS: The Gamma(min ) of all APS dispersions were below 10 mN/m.
      There was no significant difference (P> 0.05) between the Gamma(min ) of APS and
      the corresponding INS-APS. In vivo experiments showed a significant glucose level
      decrease and insulin absorption increase (P< 0.05) in the presence of APS,
      compared to the insulin solution alone. From the results, we found that the
      pulmonary edema index values of all the INSAPS groups were significant lower (P<
      0.05) than that of the insulin solution group, and there were no significant
      differences (P> 0.05) between INS/DPPC/Tyl, INS/ DPPC/PG, and the control group.
      The pulmonary edema indices and histopathological observation indicated that INS
      APS could alleviate lung injury. CONCLUSION: The most potent hypoglycemic effect
      and insulin absorption increase in this study were obtained with INS/DPPC/Tyl.
      According to the results, there was a linear correlation between the Gamma(min )
      and relative bioavailability of INS-APS, suggesting a possible effect of the
      Gamma(min ) of carriers on the in vivo absorption of insulin. APS, DPPC/Tyl, and
      DPPC/PG dispersions might be the most efficient insulin pulmonary delivery
      carriers in achieving a lower Gamma(min ), enhancing insulin absorption, and
      decreasing lung injury.

PMID- 17439734
TI  - Age-based clinical and angiographic outcomes after sirolimus-eluting stent
      implantation in patients with coronary artery disease.
AB  - BACKGROUND: Advanced age independently predicts early and late mortality and
      major adverse cardiac events (MACE) after percutaneous coronary intervention
      (PCI). Randomized clinical trials indicate that sirolimus-eluting stent (SES)
      implantation reduces target lesion revascularization (TLR), but there are limited
      data on the impact of age on outcomes following SES implantation in patients with
      coronary artery disease (CAD) in real-world practice. METHODS: A total of 333 CAD
      patients with 453 lesions were enrolled in this study. Subjects were divided into
      two groups according to age: a young group (< 65 years old, 244 patients with 369
      lesions) and elderly group (= 65 years old, 89 patients with 113 lesions).
      Clinical follow-up and quantitative coronary angiography (QCA) were performed
      seven months after PCI. RESULTS: Baseline clinical, demographic, angiographic,
      and procedural chararcteristics were similar in both groups, except that there
      were more female patients in the elderly group (21.3% vs 9.8%, P = 0.006).
      Primary success rate was similar in both groups (96.5% in young group vs 95.7% in
      elderly group, P > 0.05). During angiographic follow-up at 7 months, binary in
      stent restenosis and in-segment restenosis rates were not significantly different
      between the two groups (4.7% vs 1.8%; 9.7% vs 8.8%, P > 0.05 respectively). Both
      sub-acute and late thrombosis rates were similar in the two groups (0.3% vs 0.9%
      and 1.2% vs 0.9%, P > 0.05 respectively). TLR was not significantly different
      between the two groups (6.5% vs 3.5%; P = 0.246). The rates of bleeding, stroke,
      angina rehospitalization during the follow-up period were also similar in both
      groups (P > 0.05 respectively). CONCLUSION: Despite a high-risk clinical profile,
      coronary SES implantation can be safely and effectively performed in elderly
      patients with a similar procedural success rate, a low complication rate, and
      excellent 7-month outcomes.

PMID- 17439735
TI  - A 26-year clinical observation of splenic auto-transplantation and oesophageal
      transection anastomosis: a new treatment strategy in patients with portal
      hypertension.
AB  - BACKGROUND: Surgical treatment options for patients with cirrhosis and portal
      hypertension are complicated. In this study, we evaluated the effectiveness of a
      new treatment strategy, splenic auto-transplantation and oesophageal transection
      anastomosis. We report results from clinical observations, splenic immune
      function and portal dynamics in 274 patients. METHODS: From 1979 to 2005, 274
      cirrhosis patients with portal hypertension underwent the new treatment strategy,
      and were followed up to compare results with those patients who underwent
      traditional surgical treatment. From 1999 to 2002, a randomized controlled trial
      (RCT) was performed on 40 patients to compare their post-operative immune
      function. From 1994 to 2006, another RCT enrolled 28 patients to compare portal
      dynamics using three-dimensional dynamic contrast-enhanced magnetic resonance
      angiography (3D DEC MRA) investigation post operation. RESULTS: Among 274
      patients (mean age 41.8 years), the emergency operative mortality (4.4%),
      selective operative mortality (2.2%), complication rate (17.9%), prevalence of
      hepatic encephalopathy (< 1%), rate of portal hypertension gastritis (PHG)
      bleeding (9.1%), and morbidity of hepatic carcinoma (8%) were similar to those
      patients undergoing traditional operation; the spleen immunology function
      (Tuftsin, IgM) decreased in both groups 2 months post operation, but this
      decrease did not reach statistical significance. Through 3D DCE MRA, the cross
      sectional area and the velocity and volume of blood flow of the main portal vein
      decreased significantly after operation in both groups. The velocity and volume
      of blood flow in the auto-transplantation group was significantly lower than that
      in the control group. CONCLUSIONS: Splenic auto-transplantation and esophageal
      transection anastomosis is a safe, effective, and reasonable treatment strategy
      for patients with portal hypertension with varicial bleeding. It not only can
      correct hypersplenism, but may also achieve complete hemostasis. Spleens auto
      transplanted into the retroperitoneal space can preserve immune function and
      establish broad collateral circulation.

PMID- 17439736
TI  - Weekly gemcitabine as a radiosensitiser for the treatment of brain metastases in
      patients with non-small cell lung cancer: phase I trial.
AB  - BACKGROUND: Conventional treatment for non-small cell lung cancer (NSCLC) brain
      metastases (BM) is whole-brain radiotherapy (WBRT). The efficacy is limited. It
      might be increased by a potent radiosensitizer such as gemcitabine, which is
      believed to cross the disrupted blood-brain barrier. The primary objective of
      this study was to determine the maximum tolerated dose (MTD) of weekly
      gemcitabine given concurrently with WBRT. METHODS: Patients with BM from NSCLC
      were included. The dose of WBRT was 3750 cGy (total 15 times, 3 weeks).
      Gemcitabine was given concurrently with WBRT on days 1, 8 and 15. The starting
      dose was 400 mg/m(2), escalated by 100 mg/m(2) increments. At least three
      patients were included per level. Dose limiting toxicity (DLT) was defined as
      grade 4 hematological or grade 2 neurological toxicity. When two or more patients
      experience DLT, the MTD was reached. RESULTS: A total of 16 patients were
      included; 69% had a performance status (PS) 1 (Eastern Cooperative Oncology
      Group, ECOG). A total of 69% had concurrent active extra cranial diseases. All
      had more than 3 BM. Up to 600 mg/m(2) (level 3) no neurology toxicity was
      observed. At 600 mg/m(2) two out of 9 patients developed grade 4
      thrombocytopenia. One of the two patients' thrombocytopenia was confused with
      disseminated intravascular coagulation (DIC). At 700 mg/m(2) two out of 4
      patients developed neurotoxicities. One developed grade 3 seizure and cognitive
      disorder. Another patient developed suspected grade 2 muscle weakness.
      CONCLUSIONS: The MTD was reached at a dose of 700 mg/m(2). The dose of 600
      mg/m(2) would be considered for further study.

PMID- 17439737
TI  - Modified conditioning regimen busulfan-cyclophosphamide followed by allogeneic
      stem cell transplantation in patients with multiple myeloma.
AB  - BACKGROUND: Allogeneic stem cell transplantation is a potential curative approach
      in patients with multiple myeloma. The very high transplant related mortality
      associated with standard allogeneic stem cell transplantation is currently the
      major limitation to wider use of this potentially curative treatment modality.
      The challenge for clinical investigators is to reduce the incidence of post
      transplant complications for patients receiving autologous hematopoietic stem
      cell transplantion for multiple myeloma. In this study the toxicity and efficacy
      of modified myeloablative conditioning regimen followed by allogeneic stem cell
      transplantation was investigated in patients with multiple myeloma. METHODS: The
      conditioning regimen consisted of hydroxyurea, cytarabine, busulfan,
      cyclophosphamide, and semustine. Ten patients underwent allogeneic
      transplantation among them hydroxyurea (40 mg/kg) was administered twice on day
      10 and cytarabine (2 g/m(2)) was given on day-9, busulfan was administered orally
      in four divided doses daily for 3 days (days-8 to -6). The dose of busulfan was
      12 mg/kg in the protocol followed by cyclophosphamide intravenously over 1 hour
      on days-5 and -4 (1.8 g/m(2)), and with semustine (Me-CCNU) 250 mg/m(2) on day 
      3. RESULTS: Chimerism data were available on all patients and all patients
      achieved full donor chimerism without graft failure. Six patients had not acute
      graft-versus-host disease (GVHD, 36.4%; 95% CI: 13.9% - 38.6%). Two patients
      (18.2%) developed grade I acute GVHD (95% CI: 10.9% - 35.9%) and grade II acute
      GVHD occurred in one patient (9.1%; 95% CI: 8.4% - 32.3%). Severe grade IVa GVHD
      was seen in one patient, who died from acute GVHD. The incidence of chronic GVHD
      was 22.2% (95% CI: 11.7% - 36.7%), among them one died of severe grade IV GVHD
      and one developed multiorgan failure on day +170; the treatment-related mortality
      was 22.0% (95% CI: 10.3% - 34.1%). The overall 4-year survival rate was 67.8%
      (95% CI: 16.3% - 46.7%). The estimated 4-year progression-free survival rate was
      58.5% (95% CI: 13.7% - 41.8%). The 4-year complete remission was 72.7% (95% CI:
      27.8% - 49.6%). One patient relapsed after 4 months and achived the complete
      remission after receiving the donor lymphocyte infusion. CONCLUSIONS: Modified
      conditioning regimen busulfan-cyclophosphamide with peripheral blood stem cells +
      bone marrow cells transplantation result in a low incidence of severe GVHD with a
      relatively low treatment-related mortality, high complete remission rates and a
      long-term survival.

PMID- 17439739
TI  - XIAP as a prognostic marker of early recurrence of nonmuscular invasive bladder
      cancer.
AB  - BACKGROUND: Dysregulation of apoptosis has been implicated not only in
      carcinogenesis and tumor progression but also in tumor recurrence. We
      investigated whether the expression of X-linked inhibitor of apoptosis (XIAP)
      might predict early recurrence in patients with non-muscular invasive bladder
      cancer. METHODS: The cohort comprised 176 consecutive patients with primary
      superficial bladder cancer treated with transurethral resection.
      Immunohistochemical staining using the standard avidin-biotin-peroxidase
      technique and RT-PCR were used to detect XIAP protein and mRNA expressions in
      cancer tissues. The relationship between XIAP expression and clinicopathological
      characteristics, cancer recurrence were analyzed. RESULTS: XlAP expression was
      observed in 108 cases (61.4%) and no expression in 68. There was no correlation
      between XIAP expression rate and the tumor pathological grade, but was an
      apparent trend toward the increased XIAP levels from well (G1) to poor (G3)
      differentiated cancer. Eighty-two (46.6%) patients experienced tumor recurrence
      at a mean of 28.6 months of the follow-up; 66 of them expressed XIAP (61.1%) and
      16 were XIAP negative (23.5%). Twelve patients presented with invasive disease at
      the time of relapse and all of them expressed XIAP. Patients without XIAP
      expression or with low tumor grades had significantly higher recurrence-free
      survival than those with XIAP expression (log rank test P = 0.0015) or high tumor
      grades (log rank test P < 0.001). Multivariate analysis revealed that XIAP
      expression, tumor grade, and tumor number were independent predictors for the
      recurrence of non-muscular invasive bladder cancer (P = 0.004, 0.016, and 0.043,
      respectively). CONCLUSIONS: XIAP may be considered as a new independent
      prognostic marker for early recurrence of non-muscular invasive bladder cancer.

PMID- 17439740
TI  - PET/CT imaging of delayed radiation encephalopathy following radiotherapy for
      nasopharyngeal carcinoma.
AB  - BACKGROUND: With the significant improvement in the survival of patients with
      nasopharyngeal carcinoma (NPC) undergoing radiotherapy and the growing
      availability of the sophisticated imaging modalities, the number of radiation
      encephalopathy (RE) cases relating to NPC radiotherapy is increasing. In this
      study, we investigated the metabolic and density changes of the compromised brain
      tissues during delayed RE using a positron-emission tomography-computed
      tomography (PET/CT) to provide clinical evidences for the diagnosis of delayed RE
      following radiotherapy for NPC. METHODS: The PET/CT manifestations and the
      clinical data of 53 pathologically confirmed NPC patients with delayed RE
      following radical radiotherapy and 15 healthy volunteers were investigated. The
      standardized uptake values (SUV) of the bilateral temporal lobes, the occipital
      lobe and the brain stem were measured respectively; and then the metabolic
      reduction rate of 88 temporal lobes and 13 brain stems were calculated for a
      statistical comparison between the two groups. RESULTS: The earliest case of
      delayed RE in the investigated patients occurred 1.5 years after radiotherapy.
      Delayed RE frequently involved the inferior temporal lobe. For patients with
      delayed RE confirmed by clinical symptoms and imaging findings, PET maintained a
      100% coincidence rate with CT; however, in the 25 temporal lobes of the 35
      delayed RE patients, PET revealed obvious hypometabolic changes whereas CT
      displayed normal density. The incidence of brain stem metabolic reductions was
      24.5% (13/53) in the investigated patients, including 4 patients with
      hypometabolic changes shown by PET and negative finding shown by CT. The
      incidence of granuloma adjacent to the hypometabolic region in the temporal lobe
      was 12.5% (11/88). CONCLUSION: Delayed RE patients exhibit significant
      hypometabolic changes in the inferior temporal lobe, captured by PET much earlier
      than by CT. PET/CT offers a valuable means for the diagnosis of delayed RE in
      subacute stages and granuloma formation.

PMID- 17439741
TI  - Elevation of tumor necrosis factor-alpha, interleukin-1beta and interleukin-6
      levels in aortic intima of Chinese Guizhou minipigs with streptozotocin-induced
      diabetes.
AB  - BACKGROUND: Large animal models with toxin-mediated pancreatic damage have been
      used extensively in researches with respect to diabetes mellitus and
      cardiovascular diabetic complications. The present study aimed to establish
      Chinese Guizhou minipig models with streptozotocin (STZ)-induced diabetes and
      characterize the animal models by analyzing inflammatory cytokine levels in
      aortic wall, such as tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL
      1beta) and interleukin-6 (IL-6). METHODS: Twenty-two male Chinese Guizhou
      minipigs (age, 4 to 6 months; weight, 20 kg to 30 kg) were divided into STZ
      induced diabetic group (n = 12) and control group (n = 10). STZ (125 mg/kg) was
      administrated to induce hyperglycemia and afterwards insulin was used to control
      fasting blood glucose levels below 10 mmol/L. Oral glucose tolerance test (OGTT)
      was performed before and one month after STZ administration and serum
      concentrations of alanine transaminase, asparagine transaminase, albumin, blood
      urea nitrogen, creatinine, lipids and white blood cell count were measured before
      and six months later. Animals in both groups were euthanized after six months and
      pancreas was examined immunohistochemically for islet beta cells. Aortic intima
      of diabetic minipigs and controls was analyzed for TNF-alpha level in tissue
      conditioned medium by Western blot. TNF-alpha, IL-1beta and IL-6 mRNA levels in
      aortic intima were assayed by reverse transcription and polymerase chain reaction
      (RT-PCR). RESULTS: Significant elevation in serum glucose levels was observed one
      month and six months after STZ induction (P < 0.001) and markedly increased OGTT
      values were noted, compared with baseline data. The normal pancreas had many
      irregular sized islets and small clusters of islet beta cells, while in pancreas
      of diabetic minipigs islet beta cells almost disappeared. No statistical
      difference was notified in serum concentrations of biochemical examinations
      before and six months after STZ induction. Western blot demonstrated dramatically
      increased TNF-alpha level in aotic intima conditioned medium, and significant
      elevation of TNF-alpha, IL-1beta and IL-6 mRNA levels was revealed by RT-PCR.
      CONCLUSIONS: The present study has established Chinese Guizhou minipig models
      with STZ-induced diabetes. Inflammatory cytokines (TNF-alpha, IL-1beta and IL-6)
      significantly elevated in aortic intima of diabetic minipigs.

PMID- 17439742
TI  - Dynamic changes in the expression of growth factor receptors in the myocardium
      microvascular endothelium after murine myocardial infarction.
AB  - BACKGROUND: After myocardial infarction, specific growth factors promote cardiac
      angiogenisis, leading to a therapeutic effect. Although this effect is mediated
      by specific receptors in the endothelium of the cardiac microvasculature, few
      studies have investigated dynamic changes in their expression. We explored this
      phenomenon in a murine model. METHODS: We observed the mRNA expression of
      receptors by specific angiogenesis gene microarray at day 3 and day 7 after
      infarction. The vascular endothelial growth factor (VEGF) receptor Flk-1 was
      observed at the protein level at day 3 and day 7 by immunohistochemistry. The
      dynamic expression of fibroblast growth factor receptor-1 (FGFR-1) mRNA in the
      border zone and the noninfarcted zone at day 3, day 7, day 14, and day 42 was
      investigated by real-time PCR. Statistical significance was analyzed with SPSS
      10.0 software using one-way analysis of variance (ANOVA). RESULTS: Three days
      after infarction, 9 receptors in the border zone and 7 receptors in the
      noninfarcted zone were down-regulated. Two receptors in the infarct edge and 5
      receptors in the distant myocardium were up-regulated. However, at day 7, 11
      receptors in the border zone were up-regulated, and only one was down-regulated.
      In the border zone, Flk-1 levels decreased at day 3 but increased significantly
      at day 7. Real-time PCR showed that FGFR-1 mRNA decreased markedly in the border
      zone at day 3 but increased afterward for at least 6 weeks. In the early stage (3
      days) after infarction, the expression of receptors had decreased to some extent.
      However, at day 7, receptor expression was active and had moved from the distant
      noninfarcted zone to the border zone as a part of the acute repair process.
      CONCLUSION: Selecting the proper growth factors to target receptors with
      protective activity, and determining appropriate therapeutic timing may be
      important to the success of therapeutic angiogenesis.

PMID- 17439743
TI  - Effect of fibroblast growth factor 9 on Runx2 gene promoter activity in MC3T3-E1
      and C2C12 cells.
AB  - BACKGROUND: Fibroblast growth factor 9 (FGF9), expressed in brain, kidney and
      developing skeletal tissues, can physiologically inhibit endochondral
      ossification; but little is known about how FGF9 affects osteoblasts and its
      detailed regulatory mechanism. Here we examined the effect of FGF9 on the
      activity of the murine Runt-related transcription factor 2 (Runx2) gene promoter
      in preosteoblast MC3T3-E1 and premyoblast C2C12 cells. METHODS: Plasmids
      containing the Runx2 promoter region were transfected into MC3T3-E1 and C2C12
      cells and stably transfected cell lines were established. The method of
      luciferase reporter gene activation was used to examine the effects of FGF9 on
      the promoter activity. RESULTS: FGF9 (10 ng/ml) increased Runx2 promoter activity
      in MC3T3-E1 cells. When MC3T3-E1 cells were treated with FGF9 plus the various
      inhibitors or activator of the intracellular signaling transducation pathways,
      including 10 micromol/L U0126 (the inhibitor of mitogen-activated protein kinase
      kinase), 10 micromol/L SB203580 (the inhibitor of p38/mitogen activated protein
      kinase), or 1 micromol/L C6 ceramide (an activator of mitogen activated protein
      kinase), the luciferase expression did not change significantly compared with
      that of the cells treated with FGF9 only. However, when C2C12 cells were treated
      with 10 ng/ml FGF9, Runx2 gene promoter activity first decreased and then
      increased over a period of 1 to 5 days. Among the above inhibitors, only U0126
      (10 micromol/L) completely blocked the effects of FGF9 on Runx2 gene promoter
      activity. CONCLUSIONS: Our data showed that FGF9 can affect Runx2 gene promoter
      activity in MC3T3-E1 and C2C12 cells. The action of FGF9 appears to depend partly
      on the mitogen-activated protein kinase kinase/mitogen-activated protein kinase
      pathways in C2C12 cells.

PMID- 17439744
TI  - Enhancement of DNA vaccine-induced immune responses by a 72-bp element from SV40
      enhancer.
AB  - BACKGROUND: Although DNA vaccine is considered as the next generation of vaccine,
      most DNA vaccine candidates are still suffering from the relatively weak
      immunogenicity despite the increased dosage of plasmid DNA administered. In order
      to enhance the immune responses elicited by a codon-optimized HIV gag DNA
      vaccine, a modified plasmid vector pDRVI1.0 and a booster immunization with
      replicating Tiantan vaccinia (RTV) strain expressing the same gene were employed.
      METHODS: Vector pDRVI1.0 was constructed through inserting the 72-bp element from
      the SV40 enhancer, which was reported promoting nuclear transport of plasmid DNA,
      to the upstream of cytomegalovirus enhancer/promoter region of the plasmid vector
      pVR1012. Gene expression levels from expression plasmids based on pDRVI1.0 and
      pVR1012 were tested. Humoral and cellular immune responses induced by DNA vaccine
      alone or DNA prime-RTV boost regimen were determined in mice. RESULTS: It was
      shown that the 72-bp element significantly enhanced the gene expression level in
      non-dividing cells. gag-specific humoral and cellular immune responses induced by
      DNA vaccination were both significantly improved, while the Th1/Th2 balance was
      not obviously affected by the 72-bp element. RTV boosting further significantly
      enhanced DNA vaccine-primed antibody and T cell responses in a Th1-biased manner.
      CONCLUSIONS: The 72-bp SV40 enhancer element should be included in the DNA
      vaccine vector and RTV strain is a very efficient live vector for boosting
      immunization.

PMID- 17439745
TI  - Encapsidating artificial human papillomavirus-16 mE7 protein in human
      papillomavirus-6b L1/L2 virus like particles..
AB  - BACKGROUND: Human papillomaviruses (HPVs) can infect squamous or mucosal
      epithelia and cause cervical cancer or genital warts. Coinfection with multiple
      HPV types is a common finding of many epidemiological studies. Therefore, it is
      necessary to develop a vaccine, which can eradicate established HPV infections
      and prevent other HPV infections. In this study, we generated chimeric virus like
      particles (cVLPs) composed of HPV-6b L1, HPV-6b L2 and one artificial HPV-16 mE7
      proteins. METHODS: The artificial HPV-16 mE7 gene was designed by codon
      modification, point mutation and gene shuffling then chemically synthesized and
      subcloned behind HPV-6b L2. HPV-6b L1 and L2-mE7 were expressed in insect cells
      by using Bac-to-Bac system. The generated cVLPs were purified by CsCl gradient
      ultracentrifuge and analyzed by immunoblot, electron microscope and
      haemagglutination assay. RESULTS: The HPV-6b L1 and L2-mE7 proteins were well
      expressed in insect cells and could selfassemble into cVLPs, whose diameter was
      about 55 nm and similar to that of HPV-6b L1/L2 VLPs. Intact cVLPs could be
      recognized by H6.M48 neutralizing monoclonal antibody and HPV-6b L2 polyclonal
      antibody, while the denatured cVLPs, but not the intact cVLPs, were reactive to
      HPV-16 E7 polyclonal antibody. HPV-6b L1/L2-mE7 cVLPs haemagglutinated mouse
      erythrocytes as efficiently as HPV-6b L1/L2 VLPs did. CONCLUSIONS: The insertion
      of the 158 amino acid HPV-16 mE7 protein behind L2 did not disrupt the correct
      assembling of cVLPs. The morphological characteristics and haemagglutinating
      activity of cVLPs were similar to those of HPV-6b L1/L2 VLPs. The cVLPs retained
      conformational B cell epitopes of HPV-6 VLPs and HPV-16 mE7 protein had an
      internal location in the cVLPs. Therefore, large modified E7 protein with higher
      immunogenicity could be incorporated into cVLPs by fusing to the C-terminus of
      L2, which would help to improve the therapeutic effects of L1/L2-E7 cVLPs.

PMID- 17439747
TI  - Endogenous danger signals trigger hepatic ischemia/reperfusion injury through
      toll-like receptor 4/nuclear factor-kappa B pathway.
AB  - BACKGROUND: Restoration of blood flow to the ischemic liver lobes may
      paradoxically exacerbate tissue injury, which is called hepatic
      ischemia/reperfusion injury (IRI). Toll-like receptor 4 (TLR4), expressed on
      several liver cell types, and the nuclear factor-kappa B (NF-kappaB) signaling
      pathway are crucial to mediating hepatic inflammatory response. Because IRI is
      essentially a kind of profound acute inflammatory reaction evoked by many kinds
      of danger signals, we investigated TLR4/NF-kappaB signaling pathway activation in
      a murine model of partial hepatic IRI. METHODS: Wild-type mice (WT, C3H/HeN) or
      TLR4 mutant mice (C3H/HeJ) were subjected to 45 minutes of partial hepatic
      ischemia followed by 1 hour, 3 hours of reperfusion. Sham group accepted the same
      procedure without the obstruction of blood supply. At the end of reperfusion, the
      compromise of liver function and the histological change of liver sections were
      measured as the severity of liver injury. The level of endotoxin in the portal
      vein was measured by limulus assay. NF-kappaB activation was determined by
      electrophoretic mobility shift assay (EMSA). The levels of tumor necrosis factor
      alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in systemic blood after
      hepatic IRI were assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      The compromise of liver function and the morphological injuries in mutant mice
      were relieved more markedly than those in WT mice after partial hepatic IRI. NF
      kappaB activation in WT mice was stronger than that in TLR4 mutant mice, and both
      were stronger than those in the sham operated mice (P < 0.01). Endotoxin in each
      group was undetectable. The levels of TNF-alpha and IL-1beta in systemic blood
      were elevated in both strains, but lower in the sham operated group. These
      mediators were significantly decreased in TLR4 mutant mice compared with those in
      WT mice (P < 0.01). CONCLUSIONS: The TLR4/NF-kappaB signaling pathway may mediate
      hepatic IRI triggered by endogenous danger signals. Inhibition of the TLR4/NF
      kappaB pathway may be a potential therapeutic target for attenuating
      ischemia/reperfusion-induced tissue damage in some clinical settings.

PMID- 17439748
TI  - Smad4 and ERK2 stimulated by transforming growth factor beta1 in
      rhabdomyosarcoma.
AB  - BACKGROUND: Transforming growth factor beta (TGF-beta) plays an essential role in
      the regulation of normal physiologic processes of cells. TGF-beta has been shown
      to regulate several mitogen-activated protein kinases (MAPK) pathways in several
      epithelial cells. However, the effects of TGF-beta on soft tissue sarcoma are
      seldom reported. Our previous studies suggested that there should be some other
      signal transduction pathways besides Smads, which are important to regulate the
      growth of human embryonal rhabdomyosarcoma (RMS) cells. In the present study, we
      examined the expression and functional relations of extracellular signal
      regulated kinase 2 (ERK2) and Smad4 in human RMS tissue and a RMS cell line, RD.
      METHODS: RD cells and normal human primary skeletal myoblasts (Mb) were treated
      with TGF-beta1 to establish the expression profile of ERK2 at the mRNA and
      protein levels detected by RT-PCR and immunofluorescence. Immunohistochemistry
      was used to detect the expression of ERK2 and Smad4 in 50 tissue specimens of
      human RMS and 23 specimens of normal skeletal muscles. Follow-up of specimens was
      performed 6 months to 70 months later. RESULTS: RD cells and human RMS tissues
      showed the higher expression of ERK2 and Smad4 than the normal control, either
      the protein level or the mRNA level. And, exogenous TGF-beta1 stimulation can
      lead to higher expression of ERK2 and its nuclear translocation, so TGF-beta1 can
      also activated MAPK (ERK2) pathway, resulting in a sustained activation of ERK2
      for at least 2 hours. Immunohistochemistry analysis, however, showed that there
      was no correlation between ERK2 and Smad4 protein. The overexpression of ERK2 and
      Smad4 had no indicative effects on histological subtypes, histological grading,
      gender, age, and prognosis. CONCLUSIONS: In RMS, signaling of TGF-beta1 from cell
      surface to nucleus can also be directed through the MAPK (ERK2) pathway besides
      the TGF-beta1/Smads pathway. The activation of ERK2 by TGF-beta1 may be Smad4
      independent. Moreover, there may be some other tanglesome relationships between
      the TGF-beta1/Smads pathway and the MAPK pathway which takes part in the
      development, invasion and metastasis of tumor cells.

PMID- 17439749
TI  - R5 to X4 coreceptor switch of human immunodeficiency virus type 1 B' and B'/C
      recombinant subtype isolates in China.

PMID- 17439750
TI  - Perivascular epithelioid cell tumor of the uterus: report of three cases.

PMID- 17439751
TI  - [Nursing advanced practice: some thoughts].
AB  - In the article Advanced Nursing Practice role is discussed by a time related path
      and some general considerations on local contest. ANP is also a result of a
      disciplinary and professional development. Many forces driven changes: Health
      systems changes, new vision of Health, new education systems and some local
      challenges that imply practice revision, push to abandon or delegate some common
      nursing practices to assume other responsibilities and roles based on intra and
      inter professional collaboration as a strong value.

PMID- 17439752
TI  - [The nursing profession in the prison: a descriptive survey].
AB  - This article is to notice of the nurse's roll in the prison and the relation
      between patient prisoner - nurse. The aim of this research is to identify often
      aspect of nursing in the prison.

PMID- 17439753
TI  - [Risk management in therapeutic procedures: the integrated flowsheet. Experience
      in a CQI context].
AB  - Medication errors are an important problem in healthcare organizations. The
      Health Ministry and other government bodies have advised personnel directly
      involved in the care process as well as hospital management to adopt methods to
      prevent clinical risk. For this reason, the Sant'Andrea hospital of Rome , after
      analyzing the problem , decided to resolve it by introducing some corrective
      measures such as the integrated medication flowsheet. GOALS: To integrate the
      competence and knowledge necessary to fulfill patients' needs while safeguarding
      the different professional areas; to obtain better standards of quality , safety
      and patient satisfaction while enhancing job satisfaction and integration in all
      the professionals of the equipe.

PMID- 17439754
TI  - [Blood donation and prevention of hepatitis C. A case report from a mobile unit
      of Italian State Police].
AB  - The aim of the present study was to describe and interpret the narrative of a
      police officer's experience regarding C hepatitis. After a blood donation,
      results were positive for anti HCV. He underwent early treatment fort HCV and
      became negative about one year later. Data were collected from a patient
      interview and analysed using a phenomenological method in order to gain insight
      into the way an HCV positive patient lives. A qualitative content analysis was
      used for the content of the interview. The main findings of this study concern
      the real-life experience of C hepatitis, the nurse-patient relationship and blood
      donation as both an expression of solidarity and a means of prevention.

PMID- 17439755
TI  - [The course from Registered Nurse to Bachelor in Science of Nursing: analysis of
      four years of experience in the Nursing School of Padua University (Italy)].
AB  - This article describes the results obtained in four years of rn-bsn course in the
      nursing school of padua university. From the academic years 2001-02, 2002
      students obtained the degree, with good results (medium degree mark: 98/110).
      Student evaluation of the course was good.

PMID- 17439756
TI  - [An integrated project to prevent and minimize medication errors. The Istituti
      Ortopedici Rizzoli of Bologna's experience].
AB  - Medication errors are a well-known problem in healthcare organizations. Several
      studies have shown that medication errors and adverse drug events (ADEs) are the
      biggest causes of adverse events in hospitals. This work will present the
      Istituti Ortopedici Rizzoli of Bologna's project, which has an systemic and
      integrated approach to prevent and minimize medication errors. The project
      performed this activities: a cognitive survey to learn the nurse staff's
      knowledge and perception of risks level; educational activities to sensitize
      nurse staff; a detailed retrospective study, based on the analysis of clinical
      records, to determine the rate of medication errors in the prescription and
      transcription phases; the introduction of a unified tool for medication, which
      eliminates the transcription phase, enable the medication prescription and the
      administered drug to be recorded.

PMID- 17439757
TI  - [Health organization of continuing care communities: a new organization model for
      Public Health in Lazio region].
AB  - In this article times and spaces of care offer the opportunity to reflect on
      nursing moving from an hermeneutic perspective. Our focus has been placed on what
      always undergo the tie that exists between every doing and the con-text in which
      it happens, rather that on the differences of practices in the various places and
      times of nursing activities - home care, hospital, the outpatients' department,
      and so on. According to the hermeneutic perspective, the outcome of nursing
      relation is not exclusively the re-solution of the nursing problem of the
      patient, but also - together with all of that - the possible experience of
      identity new construction (and re-birth) that every experience of disease
      represents.

PMID- 17439758
TI  - Invasive breast cancer.

PMID- 17439759
TI  - Novel approaches to advanced breast cancer: bevacizumab and lapatinib.
AB  - New biological therapies continue to emerge in breast cancer. Recent advances
      with anti-angiogenesis therapies and anti-HER2 therapies highlight the next
      generation of treatments that will be entering clinical practice. Important
      questions regarding these targeted treatments remain, however. There are
      uncertainties as to how best to integrate new drugs into existing treatment
      algorithms, whether to use monotherapy or combination therapy with chemotherapy,
      and how to manage novel side effects seen with these agents. This review
      highlights recent advances with the anti-vascular endothelial growth factor
      antibody, bevacizumab, and the dual kinase inhibitor, lapatinib, in the treatment
      of metastatic breast cancer.

PMID- 17439760
TI  - Phyllodes tumors of the breast: natural history, diagnosis, and treatment.
AB  - Phyllodes tumors of the breast are unusual fibroepithelial tumors that exhibit a
      wide range of clinical behavior. These tumors are categorized as benign,
      borderline, or malignant based on a combination of histologic features. The
      prognosis of phyllodes tumors is favorable, with local recurrence occurring in
      approximately 15% of patients overall and distant recurrence in approximately 5%
      to 10% overall. Wide excision with a greater than 1 cm margin is definitive
      primary therapy. Adjuvant systemic therapy is of no proven value. Patients with
      locally recurrent disease should undergo wide excision of the recurrence with or
      without subsequent radiotherapy.

PMID- 17439761
TI  - Evidence and controversies in the use of post-mastectomy radiation.
AB  - Radiation after mastectomy is recommended for women with positive nodes, larger
      tumors, or positive margins. In addition to its role in reducing the risk for
      locoregional recurrence, it has an additive effect to the survival benefit seen
      with adjuvant systemic therapy. This article reviews the role of post-mastectomy
      radiation (PMRT) based on the recommendations in the 2007 NCCN Breast Cancer
      Clinical Practice Guidelines in Oncology and addresses the risk factors for
      recurrence after mastectomy. The data supporting both improvement in locoregional
      failure and survival are reviewed in detail. This article also discusses
      controversial areas in PMRT, including regional nodal radiation in women with 1
      to 3 positive lymph nodes, PMRT in node-negative women with large tumors, and
      inclusion of internal mammary nodes. The final section discusses radiation field
      design and potential complications.

PMID- 17439762
TI  - Point: Hyperthermia with radiation for chest wall recurrences.
AB  - Treatment of a locoregional recurrence of breast cancer after mastectomy remains
      a clinically challenging problem. Often these patients have undergone prior
      radiotherapy and chemotherapy. Therapeutic options usually include resection or
      additional radiation; however, the long-term control rates are often suboptimal
      with these approaches. Data from several randomized trials suggest that the
      addition of hyperthermia to radiation can increase the response rate for such
      local recurrences. Therefore, in settings where the available therapies are
      unlikely to yield local control (e.g., local/ regional recurrence after prior
      radiation), a reasonable option to consider is radiation with hyperthermia as a
      radiation sensitizer. This article reviews the rationale and supporting
      literature for this recommendation.

PMID- 17439763
TI  - Counterpoint: Hyperthermia with radiation therapy for chest wall recurrences.
AB  - The 2007 National Comprehensive Cancer Network Breast Cancer Clinical Practice
      Guidelines in Oncology include a consideration for hyperthermia (HT) and
      radiation for women with recurrent locoregional advanced breast cancers after
      first-line surgery or radiation failed. Although HT in this setting has been used
      for several decades, recent reports are few. This article reviews the data from
      several recent studies, selected because they included at least 100 patients.
      Unresolved issues of radiation dose, optimal temperature and timing of HT, and
      quality assurance problems with thermometry are apparent from these studies.
      Although clearly an effective treatment option in this clinical scenario, more
      research on HT and radiation is needed before this treatment combination can be
      considered standard care.

PMID- 17439764
TI  - Guidelines for improving breast health care in limited resource countries: the
      Breast Health Global Initiative.
AB  - Breast cancer is an increasingly urgent problem in low- and mid-level resource
      regions of the world. Despite knowing the optimal management strategy based on
      guidelines developed in wealthy countries, clinicians are forced to provide less
      than-optimal care when diagnostic or treatment resources are lacking. For this
      reason, it is important to identify which resources most effectively fill health
      care needs in limited-resource regions, where patients commonly present with more
      advanced disease at diagnosis, and to provide guidance on how new resource
      allocations should be made to maximize improvement in outcome. Established in
      2002, the Breast Health Global Initiative (BHGI) created an international health
      alliance to develop evidence-based guidelines for countries with limited
      resources to improve breast health outcomes. The BHGI serves as a program for
      international guideline development and as a hub for linkage among clinicians,
      governmental health agencies, and advocacy groups to translate guidelines into
      policy and practice. The BHGI collaborated with 12 national and international
      health organizations, cancer societies, and nongovernmental organizations to host
      2 BHGI international summits. The evidence-based BHGI guidelines, developed at
      the 2002 Global Summit, were published in 2003 as a theoretical treatise on
      international breast health care. These guidelines were then updated and expanded
      at the 2005 Global Summit into a fully comprehensive and flexible framework to
      permit incremental improvements in health care delivery, based on outcomes, cost,
      cost-effectiveness, and use of health care services.

PMID- 17439765
TI  - [Effect of combination therapy with hypothermia, magnesium and tirilazad in an
      experimental model of diffuse cerebral ischemia].
AB  - OBJECTIVE: To determine the grade of neuroprotection of combined treatment with
      moderate hypothermia, tirilazad and magnesium sulfate. Cerebral ischemia is one
      of the problems of great interest at present, with limited therapeutic measures.
      Hypothermia, one of the more efficient measures, together with neuroprotector
      pharmaceuticals, could be a valid alternative. DESIGN: Experimental study with a
      control group and two levels of application of therapeutic measures. CONTEXT:
      Experimental laboratory of the Medicine Faculty. PARTICIPANTS AND METHOD: Twenty
      eight Wistar rats underwent global cerebral ischemia of 10 minutes duration by
      the combination of bilateral carotid clamping and controlled hypotension (mean
      arterial pressure: 45 mmHg). Three groups were used: group I, normothermia
      maintenance; group II, moderate hypothermia (32-33 degrees C) for 2 hours; group
      III, hypothermia and administration of tirilazad mesylate and magnesium sulfate
      during the reperfusion and two hours after ischemia. The animals were sacrificed
      at 7 days and, after processing the tissue, the neurons preserved in layer CA1 of
      the hippocampus were counted. RESULTS: There is a significantly greater neuronal
      preservation in group III with regard to group I (55.4 +/- 5.1 versus 38.7 +/-
      8.8, p < 0.0001). If we compare groups II and III, significant differences are
      only obtained on the right side and in the hippocampus considered globally,
      favoring the group with hypothermia and drugs. When groups I and II are compared
      there are no significant differences. CONCLUSIONS: Association of moderate
      hypothermia, magnesium sulfate and tirilazad mesylate in the experimental model
      of transitory global ischemia used is confirmed as an effective neuroprotector
      measure, surpassing the degree of neuronal preservation of hypothermia alone.

PMID- 17439766
TI  - [Percutaneous tracheostomy in ventilated patients].
AB  - INTRODUCTION: Percutaneous tracheostomy is an alternative to conventional
      surgical tracheostomy. It is associated to a more feasible procedure, that is
      less invasive and linked to a lower degree of complications. Herein, we review
      our experience since the implementation of this technique in our Department.
      DESIGN: Retrospective observational. SETTING: Nineteen-bed intensive care
      department, in a general reference teaching hospital. PATIENTS AND METHOD: A
      total of 115 of 130 tracheostomies performed from 2001 to 2003 were
      retrospectively analyzed. Collected data include epidemiological information,
      reason for performing the procedure, maintenance time of artificial airway before
      the tracheostomy and type of ventilatory support or oxygen supplementation before
      and after the procedure. The modified PEEP (PEEP-mod = FiO2 x PEEP) was
      calculated, sedation level received before and 4-6 hours after the technique and
      also 24 hours later, were reviewed. Subsequent patient evolution was collected.
      INTERVENTIONS: Observational study on the results of routine procedures.
      VARIABLES OF INTEREST: Blood gases indicators of effectiveness in oxygen supply
      and the need of mechanical ventilation support. RESULTS: Median age of the 115
      reviewed patients was 65 years. The most common admission reasons were: brain
      vascular accident in 25 cases, head and neck injury in 21, cancer in 11 and
      sepsis in 10 patients. Tracheostomy was indicated because prolonged mechanical
      ventilation in 52 patients, coma in 28 and emergency or scheduled surgery in 10
      cases. Median length of stay in the ICU before tracheostomy was 14 days. Ninety
      two patients were discharged from the ICU, and 52 from the Hospital. The
      remaining patients died during their hospital stay. Serious complications
      appeared in 5 patients (4%); 3 of them were the development of fistulae and all
      of them occurred in patients in whom the tracheostomy was performed in the ICU at
      bedside. Before the procedure, 72 patients were under mechanical ventilation, but
      only 56 received ventilatory support 24 hours after tracheostomy. When PEEP-mod
      values were analyzed, first monitoring of median value was 1.6 (range 0 to 2), 4
      6 hours time median value was 2 (1.4-2.45), and 24 hours later median value was
      1.2 (0-2) (global variation, p < 0.001). CONCLUSIONS: In our experience,
      percutaneous tracheostomy performed at bedside in the ICU is an adequate solution
      with a low complication rate and its makes it possible to reduce the level of
      ventilatory support.

PMID- 17439767
TI  - [Inflammatory state in patients with atrial fibrillation before and after
      electrical cardioversion].
AB  - OBJECTIVE: To assess the inflammatory state in patients with persistent atrial
      fibrillation and to determine the predictive value in the success of
      cardioversion and recurrence at 30 days. DESIGN: Prospective observational case
      control study. PATIENTS: We included consecutively 49 patients with atrial
      fibrillation previously to scheduled electrical cardioversion in Coronary Care
      Unit. Clinical and echocardiographic variables were registered and High-sensivity
      C-reactive protein, interleukin-1beta, interleukin-6 and Tumour Necrosis Factor
      alpha were measured. At 30-days follow-up, rhythm and biomarkers were reassessed.
      As control groups, we recruited 27 healthy volunteers and 16 patients matched for
      age, gender and cardiovascular risk factors. RESULTS: Median age was 66 +/- 10
      years and 38% were women. All the markers were higher in patients than in both
      control groups (p < 0.05). FNT-alpha and Interleukin-6 levels were higher in non
      cardiovertors but only an enlarged atria was related to unsuccessful
      cardioversion (p = 0.036). High-sensivity C-reactive protein values in the higher
      cuartile tended to be related to recurrence of persistent atrial fibrillation (p
      = 0.06). CONCLUSIONS: There is an increased inflammatory state in patients with
      atrial fibrillation. FNT-alpha and Interleukin-6 levels were increased in non
      cardiovertors, but no biomarker was associated with success of cardioversion or
      rhythm state at 30-days. However, higher levels of hs-CRP showed a trend to be
      related to recurrence of atrial fibrillation.

PMID- 17439768
TI  - [Acute respiratory distress syndrome. Conclusions and perspectives in the
      future].

PMID- 17439769
TI  - [Selective digestive decontamination. Why don't we apply the evidence in the
      clinical practice?].
AB  - Selective digestive decontamination (SDD) is a prophylactic strategy whose
      objective is to reduce the incidence of infections, mainly mechanical ventilation
      associated pneumonia in patients who require intensive cares, preventing or
      eradicating the oropharyngeal and gastrointestinal carrier state of potentially
      pathogenic microorganisms. Fifty-four randomized clinical trials (RCTs) and 9
      meta-analysis have evaluated SDD. Thirty eight RCTs show a significant reduction
      of the infections and 4 of mortality. All the meta-analyses show a significant
      reduction of the infections and 5 out of the 9 meta-analyses report a significant
      reduction in mortality. Thus, 5 patients from the ICU with SDD must be treated to
      prevent pneumonia and 12 patients from the ICU should be treated to prevent one
      death. The data that show benefit of the SDD on mortality have an evidence grade
      1 or recommendation grade A (supported by at least two level 1 investigations).
      The aim of this review is to explain the pathogeny of infections in critical
      patients, describe selective digestive decontamination, analyze the evidence
      available on it efficacy and the potential adverse effects and discuss the
      reasons published by the experts who advise against the use of SDD, even though
      it is recognized as the best intervention evaluated in intensive cares to reduce
      morbidity and mortality of the infections.

PMID- 17439770
TI  - [Takotsubo cardiomyopathy: transient apical dysfunction of the left ventricle].
AB  - Transient apical dysfunction syndrome, ballooning or Takotsubo cardiomyopathy is
      a recently described syndrome. It is a disease with a partially known mechanism,
      characterized by the morphology adopted by the left ventricle secondary to
      hypokinesis and dyskinesis of the apical segments and hypercontractibility of the
      basal segments. In most of the cases published, it is a syndrome with ST segment
      elevation in the precordial leads, whose presentation form is also thoracic pain
      or dyspnea, with the possible existence of moderate elevation of cardiac
      biomarkers. On the contrary to the acute coronary syndrome, patients with left
      ventricle dysfunction do not have atherothrombotic disease in the coronary
      arteries. Furthermore, the alterations described have a reversible character.
      Some diagnostic clinical criteria have been proposed and there is presently some
      controversy on them and on the complementary examination needed to diagnose it.

PMID- 17439771
TI  - [Abdominal aorta injury secondary to closed trauma].
AB  - Traumatic injury of the abdominal aorta with total interruption of blood flow is
      uncommon. When there is total obstruction of the artery, the clinical picture is
      dramatic. The most frequent mechanism is compression due to the safety belt
      during a car accident. The patients have absent femoral and distal pulses,
      associated to neuropathy in the lower limbs. We present a case of abdominal aorta
      injury secondary to closed trauma and review the causes, presentation forms and
      management of the injury.

PMID- 17439772
TI  - [ST segment and T wave alternance during transmural myocardial ischemia].

PMID- 17439773
TI  - [Spondylitis, epidural abscess, meningitis and endophthalmitis due to
      Streptococcus agalactiae].

PMID- 17439774
TI  - [Electrocardiographic alterations mimicking ischemic heart disease in a patient
      with tricyclic antidepressive poisoning].

PMID- 17439776
TI  - [Images in intensive medicine].

PMID- 17439778
TI  - Invasive meningococcal disease at a military base in Warsaw, January 2007.

PMID- 17439779
TI  - Identification of the Swedish Chlamydia trachomatis variant among patients
      attending a STI clinic in Oslo, Norway.

PMID- 17439781
TI  - HIV-positive organs used for transplant in Italy due to human error.

PMID- 17439782
TI  - Health risks during the Cricket World Cup in the Caribbean: surveillance and
      assessment in the French departements.

PMID- 17439783
TI  - Seasonal influenza activity in Europe: declining in most countries in the West
      but increasing in the North-East.

PMID- 17439785
TI  - Outbreak of trichinellosis in Spain and Sweden due to consumption of wild boar
      meat contaminated with Trichinella britovi.

PMID- 17439786
TI  - Current measles outbreak in Serbia: a preliminary report.

PMID- 17439787
TI  - Trends in antimicrobial resistance in Europe: update of EARSS results.

PMID- 17439788
TI  - The first isolation of Panton-Valentine leukocidin (PVL) positive community
      acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in Russia.

PMID- 17439789
TI  - Outbreak of Salmonella Typhimurium infection traced to imported cured sausage
      using MLVA-subtyping.

PMID- 17439790
TI  - Tuberculosis: still a concern for all countries in Europe.

PMID- 17439791
TI  - The Stop TB Partnership for Europe: aims and principles.

PMID- 17439792
TI  - Tuberculosis outbreak linked to a pub in North Somerset, England.

PMID- 17439793
TI  - Mumps outbreak in Bulgaria, 2007: a preliminary report.

PMID- 17439795
TI  - Outbreak of severe gastroenteritis with multiple aetiologies caused by
      contaminated drinking water in Denmark, January 2007.

PMID- 17439796
TI  - Tularaemia outbreak in northern Norway.

PMID- 17439797
TI  - Laboratory-confirmed case of toxigenic Corynebacterium ulcerans.

PMID- 17439798
TI  - Local mumps outbreak in Hungary, 2007.

PMID- 17439799
TI  - An outbreak of measles in Apulia, Italy, November 2006-January 2007.

PMID- 17439800
TI  - Universal immunisation with human papillomavirus (HPV) vaccine among females aged
      12-17 recommended in Germany.

PMID- 17439801
TI  - HIV/AIDS in the Czech Republic, 2006.

PMID- 17439802
TI  - New WHO influenza vaccine recommendations for 2007-2008 season, northern
      hemisphere.

PMID- 17439803
TI  - First detected case of community-acquired methicillin-resistant Staphylococcus
      aureus skin and soft tissue infection in Italy.

PMID- 17439804
TI  - First cluster of travel-associated legionnaires' disease detected in Bulgarian
      citizens.

PMID- 17439805
TI  - European immunization week: 16-22 April.

PMID- 17439807
TI  - A hotel-based outbreak of Salmonella enterica subsp. Enterica serovar Enteritidis
      (Salmonella Enteritidis) in the United Kingdom, 2006.
AB  - An outbreak of food-borne Salmonella Enteritidis PT4 occurred in Cumbria, in
      north-west England, in the summer of 2006. Fifteen people, all with positive
      stool samples, met the case definition; three of these were admitted to hospital,
      including one patient who died. Preliminary investigations suggested a link to a
      meal served at a local hotel. A case control study was implemented, together with
      microbiological and environmental investigations. Fifteen microbiologically
      confirmed cases and 27 unmatched controls were included in the study, controls
      being randomly selected from people who had eaten at the hotel on the same day.
      The epidemiological evidence indicated a very strong association between
      infection and consumption of tiramisu made with raw shell eggs, although none
      were available for microbiological investigation. These results are in line with
      other salmonellosis outbreaks that have been associated with the use of raw shell
      eggs in food manufacturing and production. This paper highlights the continuing
      need for a greater awareness by those who work in the food industry of the health
      risks associated with the consumption of raw shell eggs.

PMID- 17439808
TI  - Community outbreak of Legionnaires disease in Vic-Gurb, Spain in October and
      November 2005.
AB  - This paper reports the investigation of a community-acquired outbreak of
      Legionnaires' disease in the municipalities of Vic and Gurb (Central Region of
      Catalonia, Spain). There were 55 cases reported in October and November 2005. An
      epidemiological and environmental investigation was undertaken. Thirty-five case
      patients (64%) lived in Vic or Gurb, while 36% had visited or worked in Vic or
      Gurb during the 10 days before onset of symptoms, but no commonly frequented
      building could be identified. Water probes for culture were obtained from 30
      cooling towers. In five cooling towers of two industrial settings in Gurb (plants
      A and B), Legionella pneumophila (Lp) serogroup 1 was present. Two Lp-1 strains
      were recovered from cooling towers in plants A and B. The Lp-1 strain from plant
      A showed a PGFE profile identical with those obtained from three patients. The
      exposure to Legionella pneumophila apparently occurred in a large area, since 43
      of the 55 cases lived, visited or worked within a distance of 1,800 m from plant
      A, and six cases in a distance between 2,500 and 3,400 m. The inspections of
      cooling towers in plant A revealed inadequate disinfectant doses of biocide, non
      existent maintenance records on weekends and wrong sample points for routine
      microbial check-ups. Weather conditions in October 2005 template temperature and
      high humidity (wind conditions are unappreciable) could have been favourable
      factors in this outbreak together with the flat terrain of Gurb and Vic area,
      explaining the extensive horizontal airborne dissemination of contaminated
      aerosols. The outbreak could have been prevented by proper and correct
      maintenance of the cooling tower at plant A.

PMID- 17439809
TI  - Outbreak of acute gastroenteritis in an Austrian boarding school, September 2006.
AB  - An outbreak of acute gastroenteritis occurred in September 2006 in a boarding
      school in eastern Austria. Of 113 cases, 101 were hospitalised. In order to
      identify the outbreak source, a retrospective cohort study on the group at risk
      was performed, including 222 pupils and 30 staff members. Food exposure in the
      canteen of the school was identified as the most relevant common link among the
      cases in the case series investigation. Although the preliminary microbiological
      investigation made Norovirus infections possible, an in-depth descriptive
      epidemiological investigation later pointed to food intoxication rather than a
      viral infection as the cause of the outbreak. The analytical epidemiological
      investigation implicated boiled rice and chicken wings served in the canteen as
      the most likely source of the outbreak. Staphylococcus aureus was identified as
      the causative agent. Further molecular characterisation revealed that the
      predominant S. aureus type in this outbreak was a new spa type, t2046. The same
      spa type was isolated from stool specimens of the majority of the cases
      investigated, from samples of the incriminated boiled rice, and also from a swab
      of a palmar skin lesion of one of the healthy kitchen workers, who is therefore
      the most likely source of contamination. This outbreak underlines again the
      importance of compliance with the basic guidelines for kitchen hygiene.

PMID- 17439810
TI  - Short summary of Swedres 2005, a report on Swedish antibiotic utilisation and
      resistance.
AB  - "Swedres 2005", the fifth report on Swedish antibiotic utilisation and resistance
      in human medicine, was presented in May 2006. Compared with the rest of Europe,
      antibiotic consumption and resistance levels in Sweden are relatively low.
      However, global travel and trade facilitate the spread of bacteria between
      countries and continents. As a consequence, also in Sweden, increasing resistance
      trends are seen for some pathogens, notably ESBL-producing enterobacteriaceae.

PMID- 17439811
TI  - The 2003 heat wave.
AB  - The July-August 2005 issue of Eurosurveillance focused on the impact on mortality
      of the 2003 heat wave in Europe, with articles that were based on various methods
      and looked at different time periods [1]. The subject of this letter is to
      assess, using a unique methodology, the excess mortality related to the 2003 heat
      wave across the continent.

PMID- 17439812
TI  - Effects of postnatal caffeine exposure on seizure susceptibility in developing
      rats.
AB  - Postnatal caffeine treatment of rats can influence brain excitability during
      development. To study the mechanism involved in the alterations of seizure
      susceptibility, we used an animal model that corresponds to the infants treated
      with caffeine for apnea of prematurity. Seizure susceptibility to four convulsant
      drugs (pentetrazol, picrotoxin, bicuculline and aminophylline) was assessed in 12
      and 25-day-old rats exposed to caffeine at a daily dose of 10 and/or 20 mg/kg
      s.c. at postnatal days 7-11. Our results demonstrated that the changes in
      generalized tonic-clonic seizures (GTCS) are more expressed than changes in
      minimal clonic seizures. There are marked differences among individual
      convulsants with the highest sensitivity of aminophylline-induced seizures and
      nearly complete resistance of bicuculline-induced seizures. The changes in
      individual models are age specific: aminophylline- and picrotoxin-induced
      seizures are more affected in 12- than in 25-day-old rats whereas PTZ-induced
      seizures are more changed by early postnatal caffeine exposure in 25- than in 12
      day-old animal. Taken together, repeated caffeine treatment from postnatal day 7
      to 11 reduces the seizure susceptibility during development and this reduction is
      also model specific.

PMID- 17439813
TI  - Apelin and vascular dysfunction in type 2 diabetes.

PMID- 17439814
TI  - The phenylpropanoid micronutrient chlorogenic acid improves clinical rating
      scores in rabbits following multiple infarct ischemic strokes: synergism with
      tissue plasminogen activator.
AB  - The present study assessed whether chlorogenic acid (CGA), a phenylpropanoid
      molecule that has multiple mechanisms of action would be useful to attenuate
      behavioral deficits associated with embolic strokes using the rabbit small clot
      embolic stroke model (RSCEM). Quantal analysis for each treatment determines the
      quantity of microclots (mg) that produce neurologic dysfunction in 50% of a group
      of animals (P(50)), with intervention considered beneficial if it increases the
      P(50) compared to controls. CGA (50 mg/kg) injected 5 min post-embolization
      significantly increased behavioral function and the P(50) to 3.61+/-0.52 mg
      (n=19) compared to 1.58+/-0.15 mg (n=26) in controls. In addition, CGA also
      increased the P(50) to 2.57+/-0.28 mg (n=18) when administered 1 h post
      embolization, but was ineffective when given 3 h following embolization
      (P(50)=1.22+/-0.24 mg, n=18). For combination studies with the thrombolytic
      tissue plasminogen activator (tPA), we used tPA at a standard dose of 3.3 mg/kg,
      which significantly increased the P(50) to 2.89+/-0.29 mg (n=17) when
      administered 1 h after embolization, but not 3 h after embolization (P(50)=1.54+/
      0.27 mg, n=18). However, when tPA (3.3 mg/kg) was combined with CGA (50 mg/kg)
      and administered 3 h following embolization, there was a significant increase in
      behavioral function as evidenced by an increase in the P(50) value to 3.40+/-0.76
      mg (n=23). In conclusion, as a mono-therapy CGA effectively reduced behavioral
      deficits when given up to 1 h following embolic strokes in rabbits. Moreover,
      there was a synergistic effect of the combination of tPA with CGA when
      administered 3 h following embolization. The results show that the therapeutic
      window for a standard effective dose of tPA could be increased by administration
      of CGA, suggesting that it may be most useful as a co-therapy with a standard
      thrombolytic treatment regimen.

PMID- 17439815
TI  - Percutaneous dynamic hip screw--an additional tip.

PMID- 17439816
TI  - A novel approach to characterize the binding orientation of lysozyme on ion
      exchange resins.
AB  - Much work has been done to qualify and quantify chromatographic adsorption and
      transportation mechanisms in different adsorber materials. An important aspect in
      all studies is the understanding of the binding mechanism between protein and
      resin on a molecular level in order to optimize processes on the level of
      adsorber design. We established a method to determine the binding orientation of
      lysozyme for different materials under various experimental conditions enabling
      us to observe changes in the mode of adsorption. We varied the protein load of
      two different adsorber types, Source 15S, a conventional cation exchange resin
      and EMD Fractogel SO(3), a tentacle-type cation exchanger. We found similar
      preferential binding sites for the interaction between lysozyme and the surface
      of these adsorbers at low surface coverage, however, the tentacle adsorber
      exhibited multi-point binding whereas the binding on Source was limited to one
      binding site only. With increasing protein density on the surface, lysozyme
      rotates from a space-consuming side-on to a space-saving end-on orientation on
      Fractogel, explaining a higher maximum binding capacity for Fractogel. This re
      orientation could not be observed for Source.

PMID- 17439817
TI  - Determination of kinetic and equilibrium regimes in the operation of polar
      organic chemical integrative samplers. Application to the passive sampling of the
      polar herbicides in aquatic environments.
AB  - This work set out the laboratory calibration of the passive samplers such as
      polar organic chemical integrative samplers (POCISs) which preconcentrate
      hydrophilic organic contaminants in aqueous medium. We compared the two different
      configurations available (i.e. pesticide and pharmaceutical POCISs) for sampling
      different classes of herbicides representative of a wide range of polarity
      (5.34>of=log Kow>or=-1.70). The results showed that pharmaceutical configuration
      was probably more convenient for sampling basic, neutral or acidic herbicides.
      Afterward, we performed a kinetic study with the pharmaceutical POCIS only. This
      calibration revealed linear and integrative uptakes of several herbicides for 21
      days. For some compounds like sulcotrione, mesotrione, deisopropylatrazine (DIA)
      and deethylatrazine (DEA), the linear uptake model was only valid for 10 days.
      Lastly, we observed an increase of the sampling rates with the hydrophobicity of
      the herbicides.

PMID- 17439818
TI  - Supramolecular assembly of VDAC in native mitochondrial outer membranes.
AB  - The voltage-dependent anion channel (VDAC) is the most abundant protein in the
      mitochondrial outer membrane (MOM). Due to its localization, VDAC is involved in
      a wide range of processes, such as passage of ATP out of mitochondria, and
      particularly plays a central role in apoptosis. Importantly, the assembly of VDAC
      provides interaction with a wide range of proteins, some implying
      oligomerization. However, many questions remain as to the VDAC structure, its
      supramolecular assembly, packing density, and oligomerization in the MOM is
      unknown. Here we report the so far highest resolution view of VDAC and its native
      supramolecular assembly. We have studied yeast MOM by high-resolution atomic
      force microscopy (AFM) in physiological buffer and found VDAC in two distinct
      types of membrane domains. We found regions where VDAC was packed at high density
      (approximately 80%), rendering the membrane a voltage-dependent molecular sieve.
      In other domains, VDAC has a low surface density (approximately 20%) and the pore
      assembly ranges from single molecules to groups of up to 20. We assume that these
      groups are mobile in the lipid bilayer and allow association and dissociation
      with the large assemblies. VDAC has no preferred oligomeric state and no long
      range order was observed in densely packed domains. High-resolution topographs
      show an eye-shaped VDAC with 3.8 nm x 2.7 nm pore dimensions. Based on the
      observed VDAC structure and the pair correlation function (PCF) analysis of the
      domain architectures, we propose a simple model that could explain the phase
      behavior of VDAC, and illustrates the sensitivity of the molecular organization
      to conditions in the cell, and the possibility for modulation of its assembly.
      The implication of VDAC in cytochrome c release from the mitochondria during cell
      apoptosis has made it a target in cancer research.

PMID- 17439820
TI  - Investigation of bacterial removal during the filtration process in constructed
      wetlands.
AB  - In this study, bacterial removal efficiencies of planted and unplanted subsurface
      vertical flow constructed wetlands are compared. Indicator organisms such as
      faecal coliforms (Escherichia coli, total coliforms) and enterococci, and a
      number of heterotrophic bacteria (heterotrophic plate counts) have been analysed
      from the influent and effluent of the constructed wetlands as well as at
      different depths (water and substrate samples). Furthermore dry matter content
      and total organic carbon (TOC) have been analysed and correlated. The
      investigated systems show a high removal rate for indicator organisms (a log
      removal rate of 2.85 for HPC, 4.35 for E. coli, 4.31 for total coliforms and 4.80
      for enterococci was observed). In general no significant difference in the
      removal efficiency of planted and unplanted vertical flow beds could be measured.
      Only enterococci measured in the substrate samples of the main layer of the
      filter could a statistically significant difference be observed.

PMID- 17439821
TI  - Development of a site-specific ecological risk assessment for contaminated sites:
      part I. A multi-criteria based system for the selection of ecotoxicological tests
      and ecological observations.
AB  - A two modules Decision Support System (DSS-ERAMANIA) was developed in order to
      support the site-specific Ecological Risk Assessment (ERA) for contaminated
      sites. Within the first module, the TRIAD and the Weight of Evidence approaches
      were used to develop a site-specific Ecological Risk Assessment framework
      including three tires of investigation. Selected ecological observations and
      ecotoxicological tests were compared according to Multi Criteria Decision
      Analysis (MCDA) methods and expert judgment, and the obtained ranking was used to
      identify a suitable set of tests, at each investigation tier, to be applied to
      the examined case study. A simplified application of the proposed methodology,
      implemented in the Module 1 of the DSS-ERA-MANIA, is described and discussed.

PMID- 17439822
TI  - A novel intermittent mechanical compression device for stasis prevention in the
      lower limbs during limited mobility situations.
AB  - INTRODUCTION: Intermittent pneumatic mechanical compression is commonly applied
      to obviate venous stasis in patients with increased risk of thromboembolism.
      Aviafit is a small battery-operated intermittent compression device using a
      patented mechanical, non-pneumatic technology. Our objective was to examine its
      ability to prevent venous stasis. MATERIALS AND METHODS: Doppler ultrasonography
      was used to determine venous hemodynamics of 22 healthy volunteers in both legs,
      before applying the Aviafit to one randomly selected leg, upon device activation
      and after 30 min. Each measurement provided values for peak flow velocity (PFV)
      and total volume flow (TVF). RESULTS: The PFV values were significantly higher in
      the treated leg upon activation of the Aviafit and at 30 min, compared to the
      baseline value and to the PFV of the untreated leg at the corresponding time
      points (p<0.001 for each). The TVF increased in the treated leg from baseline of
      48 ml/min to 56 ml/min at T0, and then gradually decreased, similar to the
      untreated leg. At T30, 64% of the treated legs had a higher TVF than their
      untreated counterparts. CONCLUSIONS: The lightweight, battery-operated and user
      friendly Aviafit can provide the same hemodynamic benefits as larger conventional
      intermittent pneumatic compression devices. Its potential advantages for
      prophylaxis of thromboembolism and increased compliance in rehabilitation and
      homecare, and for use during long periods of immobility such as during flights,
      are evident.

PMID- 17439823
TI  - Association of pulse pressure with fibrinolysis in patients with type 2 diabetes.
AB  - INTRODUCTION: Pulse pressure is a potent risk factor for atherosclerotic disease.
      The purpose of this cross-sectional study was to determine whether pulse pressure
      is associated with blood coagulation and fibrinolysis in patients with diabetes.
      MATERIALS AND METHODS: The relationships between pulse pressure and
      atherosclerotic risk factors, including blood coagulation and fibrinolysis
      markers, were investigated in subjects with type 2 diabetes. RESULTS: Pulse
      pressure was found to be significantly correlated with blood fibrinolysis
      markers, such as plasmin-alpha2-antiplasmin complex (PAP) and D-dimer, but not
      with platelets and blood coagulation markers, such as fibrinogen and thrombin
      antithrombin III complex (TAT). The mean pulse pressure levels in the highest
      tertiles of PAP and D-dimer were significantly higher than those in the lowest
      tertiles, while the differences in the mean pulse pressure levels among tertile
      groups of platelets, fibrinogen and TAT were not significant. These relationships
      of pulse pressure with PAP and D-dimer were not altered by adjustment for age,
      sex and history of therapy with antihypertensive and/or antithrombotic drugs. On
      the other hand, neither systolic nor diastolic blood pressure showed significant
      correlations with PAP, D-dimer, platelets, fibrinogen and TAT. Pulse pressure was
      also significantly correlated with age, aortic pulse wave velocity, intima-media
      thickness of the common carotid arteries and serum sialic acid. CONCLUSIONS:
      Pulse pressure is associated with blood fibrinolysis as well as atherosclerotic
      progression in patients with type 2 diabetes. The results of this study suggest
      that pulse pressure affects atherosclerotic progression through altering
      hemostatic functions in patients with diabetes.

PMID- 17439824
TI  - Staphylococcal enterotoxin B increases TIM4 expression in human dendritic cells
      that drives naive CD4 T cells to differentiate into Th2 cells.
AB  - Aberrant T helper (Th)2 polarization plays a critical role in the pathogenesis of
      allergic disorders; the etiology remains unclear. Dendritic cells (DCs) express T
      cell immunoglobulin mucin domain (TIM)4 that ligates TIM1 on CD4 T cells to drive
      them to become Th2 cells, but the pathogenic source of TIM4 is unknown. Here we
      report that a significant increase in TIM4 expression in human DCs was observed
      in response to Staphylococcal enterotoxin B (SEB) stimulation via Toll-like
      receptor (TLR)2 and nucleotide-binding oligomerization domain (NOD)1 pathway.
      Coculture SEB-conditioned DCs with naive CD4 T cells induced Th2 responses that
      could be abolished using TLR2 or NOD1 or TIM4 or TIM1 with counterpart antibodies
      or RNA interference. The results demonstrate that Staphylococcus aureus derived
      SEB promotes the TIM4 production in human DCs. The interaction between TIM4 and
      TIM1 drives naive CD4 T cells to develop to Th2 cells.

PMID- 17439826
TI  - Novel multiplex PCR for the detection of the Staphylococcus aureus superantigen
      and its application to raw meat isolates in Korea.
AB  - A multiplex PCR assay that allows for the rapid screening of the 19 genes that
      encode staphylococcal enterotoxins (SEs) (sea to see, and seg to sei), SE-like
      (SEl) toxins (sej to ser, and seu), and toxic shock syndrome toxin-1 (TSST-1)
      (tst) was developed in this study. These toxins are included in the pyrogenic
      toxin superantigen (PTSAg) family and are responsible for many diseases such as
      staphylococcal food poisoning (SFP) and TSS. The primers were designed based on
      dual priming oligonucleotide (DPO) technology to detect all of the 19 SAg genes
      in three sets of PCR. The developed multiplex PCR was applied to 143
      Staphylococcus aureus strains isolated from pork and chicken meat in Korea.
      Almost 50% of the strains possessed at least one of the 19 SAg genes. The most
      frequently found genes were seg, sei, sem, and sen (53 isolates, 37%), which were
      often found simultaneously in the same isolate. In those isolates, the seo (39
      isolates, 27%) or seu (6 isolates, 4%) genes were frequently found together and
      this combination (seg, sei, sem, sen, and seo or seu) was considered to be a part
      of the enterotoxin gene cluster (egc). The sea gene (10 isolates, 7%) was the
      gene most frequently detected out of all the classical SE genes (sea to see).
      Although these classical SEs are considered to be major etiological factors in
      SFP, newly described SE or SEl genes (seg to ser, and seu) were more frequently
      detected than the classical SE genes in this study. There was no isolate detected
      containing the seb, sec, sek, sel, or seq genes. S. aureus possessing mobile
      genetic elements known to encode these SAg genes, such as egc, were presumed to
      be widely distributed among pork and chicken meats in Korea. The multiplex PCR
      developed in this study could be applied to the investigation of SAg genes in S.
      aureus strains isolated from various sources.

PMID- 17439825
TI  - rRNA gene silencing and nucleolar dominance: insights into a chromosome-scale
      epigenetic on/off switch.
AB  - Ribosomal RNA (rRNA) gene transcription accounts for most of the RNA in
      prokaryotic and eukaryotic cells. In eukaryotes, there are hundreds (to
      thousands) of rRNA genes tandemly repeated head-to-tail within nucleolus
      organizer regions (NORs) that span millions of basepairs. These nucleolar rRNA
      genes are transcribed by RNA Polymerase I (Pol I) and their expression is
      regulated according to the physiological need for ribosomes. Regulation occurs at
      several levels, one of which is an epigenetic on/off switch that controls the
      number of active rRNA genes. Additional mechanisms then fine-tune transcription
      initiation and elongation rates to dictate the total amount of rRNA produced per
      gene. In this review, we focus on the DNA and histone modifications that comprise
      the epigenetic on/off switch. In both plants and animals, this system is
      important for controlling the dosage of active rRNA genes. The dosage control
      system is also responsible for the chromatin-mediated silencing of one parental
      set of rRNA genes in genetic hybrids, a large-scale epigenetic phenomenon known
      as nucleolar dominance.

PMID- 17439827
TI  - Obstructive jaundice caused by bile duct involvement in intra-abdominal non
      Hodgkin lymphoma: An unusual initial manifestation.

PMID- 17439828
TI  - Cutaneous T-cell and NK-cell lymphomas: the WHO-EORTC classification and the
      increasing recognition of specialized tumor types.
AB  - Cases drawn from Session 5 of the 2005 Society for Hematopathology/European
      Association for Haematopathology Workshop on progress in T-cell and natural
      killer (NK)-cell malignancies are used as a framework to review the current
      classification of T-cell and NK-cell malignancies in skin. In comparison with the
      typical pattern and course of mycosis fungoides (MF), selected variants of MF
      that can be difficult to diagnose are discussed. Cutaneous CD30+
      lymphoproliferative disorders are also presented in detail. Particular focus is
      placed on the recognition of rare but clinically more aggressive cytotoxic
      lymphomas in the skin. Overall, diagnostic pitfalls and new information regarding
      disease pathogenesis brought up by the Workshop cases are provided. In addition,
      a general approach to the diagnosis of cutaneous T-cell lymphomas is discussed.

PMID- 17439829
TI  - CD4+/CD56+ hematodermic tumor: the features of an evolving entity and its
      relationship to dendritic cells.
AB  - Described herein is the evolution in the diagnosis and classification of tumors
      that are variously known as blastic or blastoid natural killer cell lymphoma,
      CD4+/CD56+ hematodermic neoplasm, or tumors of plasmacytoid dendritic cell
      lineage. As illustrated by cases submitted to the 2005 Society for
      Hematopathology/European Association for Haematopathology Workshop, these tumors
      display a range of clinical manifestations and various morphologic and
      immunophenotypic features. Recent evidence suggests a close histogenetic
      relationship for most cases to plasmacytoid dendritic cells. We outline the
      typical presenting features and the clinical course of CD4+/CD56+ hematodermic
      tumors, including leukemic relapses with shifts to myelomonocytic
      differentiation. The currently unresolved issues are largely related to the
      limits of this entity, particularly the relationship to myeloid leukemia and
      undifferentiated blastic neoplasms, with which there is diagnostic overlap.
      Although questions remain, delineation of the CD4+/CD56+ hematodermic tumor and
      its improved recognition has already served as a catalyst toward better
      understanding of the multilineage potential of hematopoietic malignancies.

PMID- 17439830
TI  - Influence of blood collection systems on the prothrombin time and international
      sensitivity index determined with human and rabbit thromboplastin reagents.
AB  - Three brands of blood collection tubes were studied for their influence on the
      prothrombin time (PT) and international sensitivity index (ISI) for 5 commercial
      thromboplastin reagents. With all reagents, PTs were shorter in Vacutainer
      (Becton Dickinson Vacutainer Systems, Plymouth, England) samples than in S
      Monovette (Sarstedt, Numbrecht, Germany) or Venosafe (Terumo Europe, Leuven,
      Belgium) samples. ISI values were higher with Vacutainer samples than with S
      Monovette or Venosafe samples. The ISI differences between the tubes were small
      for Thromborel-S (2.1%; Dade Behring, Marburg, Germany) and Hepato Quick (1.1%;
      Diagnostica Stago, Asnieres, France; Roche Diagnostics Nederland, Almere, the
      Netherlands) but greater for Neoplastin Plus (5.5%; Diagnostica Stago; Roche
      Diagnostics Nederland), Simplastin HTF (8.3%; bioMerieux, Durham, NC), and
      Innovin (8.8%; Dade Behring). The PT and ISI differences between the tubes could
      be explained mostly by the effect of magnesium ion contamination in the sodium
      citrate solutions. When PT ratios were transformed into international normalized
      ratios (INRs) using crossover ISI (ie, samples collected with one type of tube
      and ISI determined with another collection system for the PT reagent), the
      differences in mean INRs could be approximately 10%. For ISI calibration of
      reference thromboplastins, blood collection tubes should be used with minimal
      divalent metal ion contamination of the citrate solution.

PMID- 17439831
TI  - A new automated screening assay for the diagnosis of von Willebrand disease.
AB  - A new, automated assay for von Willebrand factor (vWF) activity has recently
      become commercially available (HemosIL vWF activity assay, Instrumentation
      Laboratories, Lexington, MA). We prospectively studied 61 specimens from 58
      patients undergoing laboratory testing for suspicion of von Willebrand disease
      with this new method, in comparison with the established ristocetin cofactor
      method. Assays for factor VIII and vWF antigen were also performed using an
      established method on an MDA-180 coagulation analyzer (bioMerieux, Durham, NC)
      and a new method on an ACL TOP coagulation analyzer (Instrumentation
      Laboratories). Blood types were determined. The results showed no significant
      difference between the assays for factor VIII (mean, 97% for MDA-180 and ACL TOP;
      P = .494) or vWF antigen (mean, MDA-180, 109%; ACL TOP, 111%; P = .766). The mean
      result for the ristocetin cofactor assay was 106% vs 93% with the automated vWF
      activity (P = .007). The automated activity assay was 100% sensitive and 86%
      specific for detecting vWF abnormalities and seems to be a suitable screening
      test. Abnormal results should be followed up with a ristocetin cofactor activity
      assay for confirmation. Further study is recommended to confirm these
      conclusions.

PMID- 17439832
TI  - JAK2 V617F mutation in patients with catastrophic intra-abdominal thromboses.
AB  - Catastrophic intra-abdominal thrombosis can result from a variety of
      prothrombotic states, including polycythemia vera and essential thrombocythemia,
      both of which are frequently associated with an acquired mutation (V617F) in the
      JAK2 gene. To assess the prevalence and clinical implications of this mutation in
      the setting of intra-abdominal thrombosis, JAK2 V617F genotyping was performed in
      42 patients who had catastrophic intra-abdominal thromboses resulting in visceral
      transplants. The prevalence of V617F was compared with that of other
      prothrombotic states for which molecular testing is routinely performed. V617F
      mutations were detected in 7 patients (17%), who were not distinguishable on the
      basis of their peripheral blood cell counts. The median posttransplantation
      survival of V617F+ patients was 17.5 months, compared with 116.4 months for the
      V617F- patients (ratio, 6.6; 95% confidence interval, 6.3-7.0). These results
      highlight the diagnostic usefulness of JAK2 V617F testing in this setting and
      underscore the clinical significance of a positive result.

PMID- 17439833
TI  - Detection by immunofixation of M proteins in hypogammaglobulinemic patients with
      normal serum protein electrophoresis results.
AB  - Serum protein electrophoresis (SPE) demonstrates a monoclonal protein as an M
      spike in the majority of patients with monoclonal gammopathies. However, in
      patients with an apparently normal SPE pattern or hypogammaglobulinemia,
      immunofixation electrophoresis (IFE) can reveal an M protein. We undertook this
      study to determine the yield of reflex IFE testing in patients with
      hypogammaglobulinemia and to identify any laboratory or biochemical parameters
      that would predict a positive IFE result. We evaluated 380 patients with
      hypogammaglobulinemia and a normal SPE pattern. Of 380, 37 (9.7%) had a positive
      IFE result in serum, urine, or both. Of the other laboratory values evaluated, a
      high alpha2-globulin level with an increased alpha2-globulin/alpha1-globulin
      ratio, a low hemoglobin level, and an elevated creatinine level predicted a
      positive IFE result. There was a 2-fold increase in the odds ratio for a positive
      IFE result when the alpha2-globulin/alpha1-globulin ratio was elevated. We
      recommend reflex IFE testing in patients with hypogammaglobulinemia with a normal
      SPE pattern if any of the following are present: elevated alpha2- globulin/alpha1
      globulin ratio, low hemoglobin level, and elevated creatinine level.

PMID- 17439834
TI  - Chemokine receptors are infrequently expressed in malignant and benign
      mesothelial cells.
AB  - We studied chemokine receptor expression in malignant mesothelioma (MM), reactive
      mesothelium (RM), and leukocytes in effusions. The expression of leukocyte
      markers (CD3, CD4, CD8, CD14, CD16, and CD19) and chemokine receptors (CXCR1,
      CXCR4, CCR2, CCR5, and CCR7) was studied in 11 MM and 16 RM specimens using flow
      cytometry. RM specimens showed higher lymphocyte counts (mean rank, 17.6 vs 8.8;
      P = .004), whereas monocyte numbers were higher in MM (mean rank, 19.5 vs 10.2; P
      = .002). CXCR1 (P =.006) and CXCR4 (P = .036) expression was higher in MM
      monocytes. Chemokine receptors were infrequently expressed in MM (0-2/11
      effusions per receptor), whereas RM specimens were uniformly negative. Chemokine
      receptors are widely expressed on leukocytes in MM and RM effusions but are
      infrequently found on cells of mesothelial origin. This finding suggests a major
      role for an autocrine chemokine pathway in leukocytes but not in MM cells. The
      increased monocyte infiltration and their higher chemokine receptor expression in
      MM effusions may have a tumor-promoting rather than tumor-inhibiting effect.

PMID- 17439835
TI  - Diffuse large B-cell lymphoma initially manifesting in the bone marrow.
AB  - We histologically and immunohistochemically studied 37 cases of diffuse large B
      cell lymphoma (DLBCL) initially manifesting in the bone marrow (BM). We also
      compared these cases with the Asian variant of intravascular large B-cell
      lymphoma (AIVL). Histologically, the neoplastic cells of the BM mostly had large
      and round nuclei and formed clusters. Immunohistochemically, all cases were
      positive for B-cell markers. Factor VIII staining revealed neoplastic cells
      within the sinusoids of BM in 8 cases; however, these cells accounted for fewer
      than 20% of the overall neoplastic cells. In several cases, the neoplastic cells
      infiltrated liver, spleen, kidneys, lungs, stomach, and adrenal glands with a
      mainly leukemic and infrequently intravascular pattern. Although our cases share
      some clinical features with AIVL, we consider DLBCL initially manifesting in the
      BM to be a unique entity because the neoplastic cells proliferate mainly in BM,
      with infrequent involvement of the sinusoids and occasional leukemic infiltration
      in various organs.

PMID- 17439836
TI  - Expression of anaplastic lymphoma kinase, tyrosine-phosphorylated STAT3, and
      associated factors in pediatric anaplastic large cell lymphoma: A report from the
      children's oncology group.
AB  - In anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)
      activates (phosphorylates) signal transducer and activator of transcription 3
      (STAT3) with subsequent cytoplasmic expression, in some cases, of survivin and
      tissue inhibitor of metalloprotease 1 (TIMP1). These are inhibitors of apoptosis
      and negative prognostic factors. CD56 is also a negative prognostic marker in
      ALCL. We assayed 40 cases of predominantly ALK+ pediatric ALCL for pSTAT3,
      survivin, TIMP1, and CD56 using immunohistochemical analysis. The patients were
      derived from a Pediatric Oncology Group treatment protocol that showed 72% event
      free survival at 4 years for ALCL. The results show that in advanced-stage
      pediatric ALCL, although most tumors express ALK and a majority show activated
      STAT3, cytoplasmic localization of survivin and TIMP1 is not frequent, nor is
      expression of CD56. This may help, in part, explain the relatively good prognosis
      of pediatric ALCL.

PMID- 17439837
TI  - Prognostic implications of HER-2 status in steroid receptor-positive, lymph node
      negative breast carcinoma.
AB  - Patients with lymph node-negative breast carcinoma (LNNBC) and positive hormone
      receptor (HR) status during estrogen-based endocrine therapy have different
      prognoses. The contribution of HER-2 (human epidermal growth factor receptor-2)
      has not been extensively evaluated. We stained 230 LNNBCs for estrogen and
      progesterone receptors (ER and PR) and HER-2. HER-2 gene status was studied in
      150 randomly selected tumors by chromogenic in situ hybridization and cases with
      discordant or nondefinitive results by fluorescence in situ hybridization.
      Patients with ER+ and/or PR+ tumors were treated with tamoxifen. We found
      positive expression of ER, PR, and HER-2 in 73.7%, 67%, and 27.8%, respectively,
      and HER-2 amplification in 18.0%. Poorer outcome was seen for patients with ER+
      and/or PR+/HER-2 overexpressing tumors and as a trend for patients with HER-2
      amplification. ER/PR and HER-2 expression showed an independent prognostic value.
      In LNNBCs with positive HR status, HER-2 overexpression and/or amplification
      confer an aggressive tumor phenotype, and this might be related to tamoxifen
      unresponsiveness.

PMID- 17439838
TI  - Immunohistochemical evaluation of necrotic malignant melanomas.
AB  - We evaluated 35 cases of malignant melanomas with substantial necrosis
      immunostained with S-100, HMB-45, Melan-A, tyrosinase, PNL2, and microphthalmia
      transcription factor (MITF). Staining patterns were evaluated in viable and
      necrotic areas of the tumors. S-100 was the most sensitive marker (97%) in the
      viable tumors, but necrotic areas demonstrated nonspecific staining. Viable
      tumors stained variably for HMB-45 (25 [71%]), Melan-A (28 [80%]), tyrosinase (30
      [86%]), and PNL2 (23 [66%]). Necrotic areas focally reacted to the same
      antibodies. The necrotic areas that retained immunoreactivity for these markers
      corresponded to areas where the outline of the tumor cells could still be
      recognized as ghost cells on the H&E-stained section. Areas that showed complete
      coagulative necrosis were negative for melanoma markers. MITF variably stained in
      the viable tumors but was completely negative in necrotic areas. Our study
      demonstrated that a combination of antibodies to HMB-45, tyrosinase, and PNL2
      detected melanocytic differentiation in necrotic areas in 80% of cases.

PMID- 17439839
TI  - Hyaline globules (thanatosomes) in gastrointestinal epithelium: pathophysiologic
      correlations.
AB  - Hyaline globules (HGs; thanatosomes) are well-defined morphologic and functional
      entities representing a degenerative phenomenon common to all cell types. We
      present the first quantitative and qualitative study of HGs in normal and
      pathologic gastrointestinal (GI) epithelium from a series of 2,230 biopsies. HGs
      were very rarely found in normal epithelium (1.1%), but their number increased
      significantly in specimens with ischemic injury (47%) and benign regenerative
      proliferation (70%). Their incidence in adenomatous polyps and adenocarcinomas
      was about 11% to 27%. Of the HGs, 2.9% contained nuclear fragments. Our results
      entirely support the unifying morphogenetic concept for HGs. The role of 2
      obligatory morphogenetic factors for the generation of thanatosomes (propensity
      to apoptosis and heterophagy/autophagy) is confirmed. The nature of the third
      factor, ischemic conditions, is specified. Although a nonspecific microscopic
      phenomenon, HGs in the GI tract represented a relatively constant and useful
      histologic marker of enhanced cell turnover and ischemic injury.

PMID- 17439840
TI  - Oral lichen planus and chronic hepatitis C: a controversial association.
AB  - Our aim was to study the possible association between oral lichen planus and
      chronic hepatitis C in patients from the state of Minas Gerais, Brazil. Two
      groups of patients were studied: group 1, 50 patients with oral lichen planus
      evaluated for the presence of chronic hepatitis C; and group 2, 215 patients with
      chronic hepatitis C examined for evidence of oral lichen planus. Diagnosis of
      oral lichen planus in both groups was based on clinical and histologic findings.
      One case of chronic hepatitis C was diagnosed in group 1 (2.0%), which was not
      considered statistically significant (P = .464). In group 2, the prevalence of
      oral lichen planus was 2.3% (5 cases), which showed statistical significance (P =
      .002). Although our results suggest oral lichen planus as an extrahepatic
      manifestation of chronic hepatitis C in the studied population, the association
      between these two entities should be further investigated.

PMID- 17439841
TI  - The relationship of community biopsy-diagnosed cervical intraepithelial neoplasia
      grade 2 to the quality control pathology-reviewed diagnoses: an ALTS report.
AB  - We examined the predictors (cytologic interpretations, pathology review, human
      papillomavirus [HPV] testing results, and colposcopic impressions) of precancer
      among 545 women with clinical center biopsy diagnoses of cervical intraepithelial
      neoplasia (CIN) 2 in the ASCUS LSIL Triage Study. Among women with a CIN 2 biopsy
      result, there was an increasing likelihood that the loop electrosurgical excision
      procedure (LEEP) tissue sample was diagnosed as precancer (CIN 3) with an
      increasing number of clinical risk factors of cervical precancer (high-grade
      squamous intraepithelial lesion [HSIL] cytology, high-grade colposcopy, detection
      of HPV type 16; Ptrend < .0005). In a multivariate model, using a case definition
      of worst histologic diagnosis made by the quality control pathology review of
      biopsy and LEEP tissue samples, HPV-16 was positively associated (odds ratio
      [OR], 4.8; 95% confidence interval [CI], 2.6-8.8) with a CIN 3 diagnosis, whereas
      testing negative for HPV or positive for noncarcinogenic HPV types was negatively
      associated (OR, 0.32; 95% CI, 0.14-0.75) with a CIN 3 diagnosis. Although we
      found clear evidence that HPV-16 detection helped clarify whether a biopsy
      specimen diagnosed as CIN 2 represented HPV infection or cervical precancer, this
      relationship was not sufficiently robust to be clinically useful for reducing the
      overtreatment of women with HPV infection.

PMID- 17439842
TI  - Normal variation in intraepithelial lymphocytes of the terminal ileum.
AB  - The number of intraepithelial lymphocytes (IELs) is often increased in the
      terminal ileum of patients with immune-mediated inflammatory diseases of the
      colon. However, data regarding their number in normal ileal mucosa of
      asymptomatic patients are lacking. We aimed to establish the acceptable range of
      IELs in biopsy specimens of normal ileal mucosa. Ileal mucosal biopsy specimens
      obtained during colonoscopy of 61 asymptomatic patients without endoscopic or
      pathologic evidence of colitis were immunostained for CD3 to assess the number of
      IELs present in each specimen. CD3+ lymphocytes were counted in 3 well-oriented
      villi and results expressed as the average for each biopsy specimen. The study
      group included 25 males and 36 females, ranging in age from 10 to 84 years (mean,
      44.4 years). The mean +/- SD number of ileal CD3+ cells per 100 enterocytes for
      the group was 3.8 +/- 2 (median, 3; range, 0-9). In addition, there was a
      significant inverse relationship between the number of villus IELs and increasing
      age. Occasional IELs (approximately 4/100 villus enterocytes) are normally
      present in ileal biopsy specimens from asymptomatic patients without colitis. One
      should avoid overinterpreting the importance of occasional IELs in ileal biopsy
      specimens from asymptomatic patients.

PMID- 17439843
TI  - Loss of raf-1 kinase inhibitor protein expression is associated with tumor
      progression and metastasis in colorectal cancer.
AB  - Raf-1 kinase inhibitor protein (RKIP) is known as a critical down-regulator of
      the mitogen-activated protein kinase signaling pathway and a potential molecular
      determinant of malignant metastasis. The aim of this study was to determine the
      prognostic significance of RKIP expression in colorectal cancer (CRC).
      Immunohistochemical staining for RKIP was performed on a tissue microarray
      comprising 1,197 mismatch repair (MMR)-proficient and 141 MMRdeficient CRCs. The
      association of RKIP with clinicopathologic features was analyzed. Loss of
      cytoplasmic RKIP was associated with distant metastasis (P = .038), higher N
      stage (P = .032), vascular invasion (P = .01), and worse survival (P = .001) in
      the MMR-proficient group. In MMR-deficient CRCs, loss of cytoplasmic RKIP was
      associated with distant metastasis (P = .043) and independently predicted worse
      survival (P = .004). Methylation analysis of 28 cases showed that loss of RKIP
      expression is unlikely to be due to promoter methylation.Loss of RKIP expression
      is a marker of tumor progression and distant metastasis in MMR-proficient and MMR
      deficient CRCs.

PMID- 17439844
TI  - Extreme sex ratio variation in relation to change in condition around conception.
AB  - Adaptive theory predicts that mothers would be advantaged by adjusting the sex
      ratio of their offspring in relation to their offspring's future reproductive
      success. Studies investigating sex ratio variation in mammals have produced
      notoriously inconsistent results, although recent studies suggest more
      consistency if sex ratio variation is related to maternal condition at
      conception, potentially mediated by changes in circulating glucose level.
      Consequently, we hypothesized that change in condition might better predict sex
      ratio variation than condition per se. Here, we investigate sex ratio variation
      in feral horses (Equus caballus), where sex ratio variation was previously shown
      to be related to maternal condition at conception. We used condition measures
      before and after conception to measure the change in condition around conception
      in individual mothers. The relationship with sex ratio was substantially more
      extreme than previously reported: 3% of females losing condition gave birth to a
      son, whereas 80% of those females that were gaining condition gave birth to a
      son. Change in condition is more predictive of sex ratio than actual condition,
      supporting previous studies, and shows the most extreme variation in mammals ever
      reported.

PMID- 17439845
TI  - Primates follow the 'island rule': implications for interpreting Homo
      floresiensis.
AB  - When the diminutive skeleton of Homo floresiensis was found on the Indonesian
      island of Flores, it was interpreted as an island dwarf, conforming to the
      'island rule' that large animals evolve smaller size on islands, but small
      animals tend to get larger. However, previous studies of the island rule have not
      included primates, so the extent to which insular primate populations undergo
      size change was unknown. We use a comparative database of 39 independently
      derived island endemic primate species and subspecies to demonstrate that
      primates do conform to the island rule: small-bodied primates tend to get larger
      on islands, and large-bodied primates get smaller. Furthermore, larger species
      undergo a proportionally greater reduction in size on islands.

PMID- 17439846
TI  - The benefits of bathing buds: water calyces protect flowers from a
      microlepidopteran herbivore.
AB  - Protective floral structures may evolve in response to the negative effects of
      floral herbivores. For example, water calyces--liquid-filled, cup-like structures
      resulting from the fusion of sepals--may reduce floral herbivory by submerging
      buds during their development. Our observations of a water-calyx plant,
      Chrysothemis friedrichsthaliana (Gesneriaceae), revealed that buds were
      frequently attacked by ovipositing moths (Alucitidae), whose larvae consumed
      anthers and stigmas before corollas opened. Almost 25% of per-plant flower
      production was destroyed by alucitid larvae over two seasons, far exceeding the
      losses to all other floral herbivores combined. Experimental manipulation of
      water levels in calyces showed that a liquid barrier over buds halved per-flower
      alucitid egg deposition and subsequent herbivory, relative to buds in calyces
      without water. Thus, C. friedrichsthaliana's water calyx helps protect buds from
      a highly detrimental floral herbivore. Our findings support claims that sepal
      morphology is largely influenced by selection to reduce floral herbivory, and
      that these pressures can result in novel morphological adaptations.

PMID- 17439847
TI  - Elevated frequency of abnormalities in barn swallows from Chernobyl.
AB  - Ever since the Chernobyl accident in 1986, that contaminated vast areas in
      surrounding countries with radiation, abnormalities and birth defects have been
      reported in human populations. Recently, several studies suggested that the
      elevated frequency of such abnormalities can be attributed to poverty and stress
      in affected human populations. Here, we present long-term results for a free
      living population of barn swallows, Hirundo rustica, demonstrating the presence
      of 11 morphological abnormalities in populations around Chernobyl, but much less
      frequently in an uncontaminated Ukrainian control population and three more
      distant control populations. The presence of these abnormalities in barn swallows
      is associated with reduced viability. These findings demonstrate a link between
      morphological abnormalities and radiation in an animal population that cannot be
      attributed to poverty and stress. The most parsimonious hypothesis for
      abnormalities in animal and human populations alike is that the effects are
      caused by the same underlying cause, viz. radiation derived from the Chernobyl
      accident.

PMID- 17439848
TI  - Orangutans use compliant branches to lower the energetic cost of locomotion.
AB  - Within the forest canopy, the shortest gaps between tree crowns lie between
      slender terminal branches. While the compliance of these supports has previously
      been shown to increase the energetic cost of gap crossing in arboreal animals
      (e.g. Alexander 1991 Z. Morphol. Anthropol. 78, 315-320; Demes et al. 1995 Am. J.
      Phys. Anthropol. 96, 419-429), field observations suggest that some primates may
      be able to use support compliance to increase the energetic efficiency of
      locomotion. Here, we calculate the energetic cost of alternative methods of gap
      crossing in orangutans (Pongo abelii). Tree sway (in which orangutans oscillate a
      compliant tree trunk with increasing magnitude to bridge a gap) was found to be
      less than half as costly as jumping, and an order of magnitude less costly than
      descending the tree, walking to the vine and climbing it. Observations of wild
      orangutans suggest that they actually use support compliance in many aspects of
      their locomotor behaviour. This study seems to be the first to show that elastic
      compliance in arboreal supports can be used to reduce the energetic cost of gap
      crossing.

PMID- 17439849
TI  - The evolution of sexual dimorphism in parasitic cuckoos: sexual selection or
      coevolution?
AB  - Sexual dimorphism is ubiquitous in animals and can result from selection pressure
      on one or both sexes. Sexual selection has become the predominant explanation for
      the evolution of sexual dimorphism, with strong selection on size-related mating
      success in males being the most common situation. The cuckoos (family Cuculidae)
      provide an exceptional case in which both sexes of many species are freed from
      the burden of parental care but where coevolution between parasitic cuckoos and
      their hosts also results in intense selection. Here, we show that size and
      plumage differences between the sexes in parasitic cuckoos are more likely the
      result of coevolution than sexual selection. While both sexes changed in size as
      brood parasitism evolved, we find no evidence for selection on males to become
      larger. Rather, our analysis indicates stronger selection on parasitic females to
      become smaller, resulting in a shift from dimorphism with larger females in
      cuckoos with parental care to dimorphism with larger males in parasitic species.
      In addition, the evolution of brood parasitism was associated with more cryptic
      plumage in both sexes, but especially in females, a result that contrasts with
      the strong plumage dimorphism seen in some other parasitic birds. Examination of
      the three independent origins of brood parasitism suggests that different
      parasitic cuckoo lineages followed divergent evolutionary pathways to successful
      brood parasitism. These results argue for the powerful role of parasite-host
      coevolution in shaping cuckoo life histories in general and sexual dimorphism in
      particular.

PMID- 17439850
TI  - Survival against the odds: ontogenetic changes in selective pressure mediate
      growth-mortality trade-offs in a marine fish.
AB  - For organisms with complex life cycles, variation among individuals in traits
      associated with survival in one life-history stage can strongly affect the
      performance in subsequent stages with important repercussions on population
      dynamics. To identify which individual attributes are the most influential in
      determining patterns of survival in a cohort of reef fish, we compared the
      characteristics of Pomacentrus amboinensis surviving early juvenile stages on the
      reef with those of the cohort from which they originated. Individuals were
      collected at hatching, the end of the planktonic phase, and two, three, four, six
      and eight weeks post-settlement. Information stored in the otoliths of individual
      fish revealed strong carry-over effects of larval condition at hatching on
      juvenile survival, weeks after settlement (i.e. smaller-is-better). Among the
      traits examined, planktonic growth history was, by far, the most influential and
      long-lasting trait associated with juvenile persistence in reef habitats.
      However, otolith increments suggested that larval growth rate may not be
      maintained during early juvenile life, when selective mortality swiftly reverses
      its direction. These changes in selective pressure may mediate growth-mortality
      trade-offs between predation and starvation risks during early juvenile life.
      Ontogenetic changes in the shape of selectivity may be a mechanism maintaining
      phenotypic variation in growth rate and size within a population.

PMID- 17439851
TI  - Virus infection causes specific learning deficits in honeybee foragers.
AB  - In both mammals and invertebrates, virus infections can impair a broad spectrum
      of physiological functions including learning and memory formation. In contrast
      to the knowledge on the conserved mechanisms underlying learning, the effects of
      virus infection on different aspects of learning are barely known. We use the
      honeybee (Apis mellifera), a well-established model system for studying learning,
      to investigate the impact of deformed wing virus (DWV) on learning. Injection of
      DWV into the haemolymph of forager leads to a RT-PCR detectable DWV signal after
      3 days. The detailed behavioural analysis of DWV-infected honeybees shows an
      increased responsiveness to water and low sucrose concentrations, an impaired
      associative learning and memory formation, but intact non-associative learning
      like sensitization and habituation. This contradicts all present studies in non
      infected bees, where increased sucrose responsiveness is linked to improved
      associative learning and to changes in non-associative learning. Thus, DWV seems
      to interfere with molecular mechanism of learning by yet unknown processes that
      may include viral effects on the immune system and on gene expression.

PMID- 17439852
TI  - The parasitic chytrid, Zygorhizidium, facilitates the growth of the cladoceran
      zooplankter, Daphnia, in cultures of the inedible alga, Asterionella.
AB  - In food-web studies, parasites are often ignored owing to their insignificant
      biomass. We provide evidence that parasites may affect trophic transfer in
      aquatic food webs. Many phytoplankton species are susceptible to parasitic fungi
      (chytrids). Chytrid infections of diatoms in lakes may reach epidemic proportions
      during diatom spring blooms, so that numerous free-swimming fungal zoospores (2-3
      microm in diameter) are produced. Analysis shows that these zoospores are rich in
      polyunsaturated fatty acids and sterols (particularly cholesterol), which
      indicates that they provide excellent food for zooplankters such as Daphnia. In
      life-table experiments using the large diatom Asterionella formosa as food,
      Daphnia growth increased significantly in treatments where a parasite was
      present. By grazing on the zoospores, Daphnia acquired important supplementary
      nutrients and were able to grow. When large inedible algae are infected by
      parasites, nutrients within the algal cells are consumed by these chytrids, some
      of which, in turn, are grazed by Daphnia. Thus, chytrids transfer energy and
      nutrients from their hosts to zooplankton. This study suggests that parasitic
      fungi alter trophic relationships in freshwater ecosystems and may be the
      important components in shaping the community and the food-web dynamics of lakes.

PMID- 17439853
TI  - Mitigation of indirect environmental effects of GM crops.
AB  - Currently, the UK has no procedure for the approval of novel agricultural
      practices that is based on environmental risk management principles. Here, we
      make a first application of the 'bow-tie' risk management approach in
      agriculture, for assessment of land use changes, in a case study of the
      introduction of genetically modified herbicide tolerant (GMHT) sugar beet. There
      are agronomic and economic benefits, but indirect environmental harm from
      increased weed control is a hazard. The Farm Scale Evaluation (FSE) trials
      demonstrated reduced broad-leaved weed biomass and seed production at the field
      scale. The simplest mitigation measure is to leave a proportion of rows unsprayed
      in each GMHT crop field. Our calculations, based on FSE data, show that a maximum
      of 2% of field area left unsprayed is required to mitigate weed seed production
      and 4% to mitigate weed biomass production. Tilled margin effects could simply be
      mitigated by increasing the margin width from 0.5 to 1.5 m. Such changes are
      cheap and simple to implement in farming practices. This case study demonstrates
      the usefulness of the bow-tie risk management approach and the transparency with
      which hazards can be addressed. If adopted generally, it would help to enable
      agriculture to adopt new practices with due environmental precaution.

PMID- 17439854
TI  - Carotenoids, oxidative stress and female mating preference for longer lived
      males.
AB  - Some of the most spectacular exaggerated sexual ornaments are carotenoid
      dependent. It has been suggested that such ornaments have evolved because
      carotenoid pigments are limiting for both signal expression and in their role as
      antioxidants and immunostimulants. An implicit assumption of this hypothesis is
      that males which can afford to produce more elaborate carotenoid-dependent
      displays are signalling their enhanced ability to resist parasites, disease or
      oxidative stress and hence would be predicted to live longer. Therefore, in
      species with carotenoid-dependent ornaments where a parent's future longevity is
      crucial for determining offspring survival, there should be a mating preference
      for partners that present the lowest risk of mortality during the breeding
      attempt, as signalled by the ability to allocate carotenoids to sexual displays.
      In an experimental study using three-spined sticklebacks (Gasterosteus
      aculeatus), we show that when dietary carotenoid intake is limited, males attempt
      to maintain their sexual ornament at the expense of body carotenoids and hence
      suffer from reduced reproductive investment and a shorter lifespan. These males
      also suffer from an increased susceptibility to oxidative stress, suggesting that
      this may constitute the mechanism underlying the increased rate of ageing.
      Furthermore, in pairwise mate-choice trials, females preferred males that had a
      greater access to carotenoids and chance of surviving the breeding season,
      suggesting that females can make adaptive mate choice decisions based on a male's
      carotenoid status and potential future longevity.

PMID- 17439855
TI  - Species-specific acquisition and consolidation of long-term memory in parasitic
      wasps.
AB  - Long-term memory (LTM) formation usually requires repeated, spaced learning
      events and is achieved by the synthesis of specific proteins. Other memory forms
      require a single learning experience and are independent of protein synthesis. We
      investigated in two closely related parasitic wasp species, Cotesia glomerata and
      Cotesia rubecula, whether natural differences in foraging behaviour are
      correlated with differences in LTM acquisition and formation. These parasitic
      wasp species lay their eggs in young caterpillars of pierid butterflies and can
      learn to associate plant odours with a successful egg laying experience on
      caterpillars on the odour-producing plant. We used a classical conditioning set
      up, while interfering with LTM formation through translation or transcription
      inhibitors. We show here that C. rubecula formed LTM after three spaced learning
      trials, whereas C. glomerata required only a single trial for LTM formation.
      After three spaced learning trials, LTM formation was complete within 4 h in C.
      glomerata, whereas in C. rubecula, LTM formation took 3 days. Linking
      neurobiology with ecology, we argue that this species-specific difference in LTM
      acquisition and formation is adaptive given the extreme differences in both the
      number of foraging decisions of the two wasp species and in the spatial
      distributions of their respective hosts in nature.

PMID- 17439856
TI  - Origins of radial symmetry identified in an echinoderm during adult development
      and the inferred axes of ancestral bilateral symmetry.
AB  - How the radial body plan of echinoderms is related to the bilateral body plan of
      their deuterostome relatives, the hemichordates and the chordates, has been a
      long-standing problem. Now, using direct development in a sea urchin, I show that
      the first radially arranged structures, the five primary podia, form from a
      dorsal and a ventral hydrocoele at the oral end of the archenteron. There is a
      bilateral plane of symmetry through the podia, the mouth, the archenteron and the
      blastopore. This adult bilateral plane is thus homologous with the bilateral
      plane of bilateral metazoans and a relationship between the radial and bilateral
      body plans is identified. I conclude that echinoderms retain and use the
      bilateral patterning genes of the common deuterostome ancestor. Homologies with
      the early echinoderms of the Cambrian era and between the dorsal hydrocoele, the
      chordate notochord and the proboscis coelom of hemichordates become evident.

PMID- 17439857
TI  - Multiple breeders, breeder shifts and inclusive fitness returns in an ant.
AB  - In social insects, colonies may contain multiple reproductively active queens.
      This leads to potential conflicts over the apportionment of brood maternity,
      especially with respect to the production of reproductive offspring. We
      investigated reproductive partitioning in offspring females (gynes) and workers
      in the ant Formica fusca, and combined this information with data on the genetic
      returns gained by workers. Our results provide the first evidence that
      differential reproductive partitioning among breeders can enhance the inclusive
      fitness returns for sterile individuals that tend non-descendant offspring. Two
      aspects of reproductive partitioning contribute to this outcome. First,
      significantly fewer mother queens contribute to gyne (new reproductive females)
      than to worker brood, such that relatedness increases from worker to gyne brood.
      Second, and more importantly, adult workers were significantly more related to
      the reproductive brood raised by the colony, than to the contemporary worker
      brood. Thus, the observed breeder shift leads to genetic benefits for the adult
      workers that tend the brood. Our results also have repercussions for genetic
      population analyses. Given the observed pattern of reproductive partitioning,
      estimates of effective population size based on worker and gyne samples are not
      interchangeable.

PMID- 17439858
TI  - Infection dynamics: from organ to host population.
AB  - A symposium discussing collaborative research work on infectious diseases
      dynamics was held at Queens' College, University of Cambridge on 25 October 2006.

PMID- 17439859
TI  - Tensile and dynamic mechanical analysis of the distal portion of mussel (Mytilus
      edulis) byssal threads.
AB  - Dynamic mechanical analysis was used to record the behaviour of hydrated and
      dehydrated byssal threads under tensile stress and during dynamic thermal
      cycling. Fresh byssi, and byssi aged two weeks prior to testing, were used to
      further study the effects of age on the mechanical properties of this material.
      It was found that while older threads demonstrated increased stiffness, age did
      not necessarily affect their ultimate tensile strength. Dehydration had a more
      pronounced effect on thread stiffness and also increased the ultimate strength of
      the material. In their dry state, byssal threads displayed multiple yield points
      under tension and these, it is suggested, could equate to different phases within
      the bulk of the material. Dynamic analysis revealed glass transition (Tg) and
      ecologically relevant operational temperatures for byssi, where their modulus
      (E') remained constant. These discoveries are related to the ecological function
      of byssal threads and to the emerging field of biomimetics.

PMID- 17439860
TI  - Bile acids as constituents for dental composites: in vitro cytotoxicity of
      (meth)acrylate and other ester derivatives of bile acids.
AB  - Methacrylic derivatives of bile acids have been synthesized for use as monomers
      in dental composites. Polymeric dental materials are known to leach cytotoxic
      unreacted monomers and degradation products. In this study, the in vitro
      cytotoxicity of bile acids and their derivatives towards 3T3 fibroblasts has been
      evaluated by colorimetric MTT assay and compared with that of the common dental
      monomers BisGMA, UDMA and TEGDMA. In general, the bile acids and their
      derivatives induced mitochondrial dysfunction at similar or higher concentrations
      than the commercial dental monomers. Certain monomers did not influence MTT
      response over their entire range of solubility.

PMID- 17439861
TI  - A system's view of the evolution of life.
AB  - Previous treatments of biological evolution have concentrated upon either the
      general appearance or habits of organisms or the sequences of molecules, such as
      their proteins and DNA (RNA), within species. There is no consideration of the
      changing relationship of the chemistry of organisms to the elements and energy
      available from the environment. In essence, organisms at all times had to
      accumulate certain elements while rejecting others. Central to accumulation were
      C, N, H, P, S, K, Mg and Fe while, as ions, Na, Cl, Ca and other heavy metals
      were largely rejected. In order to form the vital biopolymers, C and H, from CO2
      and H2O, had to be combined generating oxygen. The oxygen then slowly oxidized
      the environment over long periods of time. These environmental changes were
      relatively rapid, unconstrained and continuous, and they imposed a necessary
      sequential adaptation by organisms while increasing the use of energy. Then,
      evolution has a chemical direction in a combined organism/environment ecosystem.
      Joint organization of the initial reductive chemistry of cells and the later need
      to handle oxidative chemistry has also forced the complexity of chemistry of
      organism in compartments. The complexity increased to take full advantage of the
      environment from bacteria to humans in a logical, physical, compartmental and
      chemical sequence of the whole system. In one sense, rejected material can be
      looked upon as waste and, in the context of this article, leads to the
      consideration of the importance of waste from the activities of humankind.

PMID- 17439862
TI  - Why not the private practice of addictionology?.

PMID- 17439863
TI  - Buprenorphine treatment: factors and first-hand experiences for providers to
      consider.
AB  - The viability of using buprenorphine to treat opiate dependence was well
      documented prior to federal approval in October 2002. What has been lacking in
      the literature is "hands-on" experience of providers from a clinical management
      and practice management perspective. This article adds to the knowledge base by
      providing information about buprenorphine treatment as well as anecdotes from
      patients treated by the authors, leading to a detailed list of factors worth
      considering for the treatment provider contemplating adding an opiate-addicted
      population to an existing treatment base.

PMID- 17439864
TI  - Correlation between high methadone doses and methadone serum levels in methadone
      maintenance treatment (MMT) patients.
AB  - AIMS: To evaluate the relation between high methadone doses and methadone serum
      levels in MMT patients. DESIGN: One hundred fifty-one steady methadone-dose
      patients were evaluated for methadone serum levels using GCMS. Urine samples
      during the month prior to the study-day were analysed and defined as positive if
      any sample was positive for any drug. FINDINGS: Methadone dose correlated with
      methadone serum levels (Pearson R = 0.36, P < 0.0005). In 53 patients with no
      drug abuse, correlation was stronger (R = 0.53, P < 0.0005) than in 98 patients
      with any drug abuse (R = 0.25, P = 0.01). CONCLUSIONS: We extended the well
      established correlation between methadone doses and serum levels in patients
      receiving low or moderate (60 to 120 mg/day) to high methadone doses (up to 290
      mg/day).

PMID- 17439865
TI  - Primary care affiliations of adults in a methadone program with onsite care.
AB  - Methadone maintenance treatment programs (MMTP) often provide onsite primary
      care. It is unclear whether patients in these settings consider the MMTP their
      usual source of care. We conducted cross-sectional interviews of 62 adults in an
      inner-city MMTP with onsite primary care to determine their usual source of care.
      Program enrollment ranged from 1 to 27 years (median, 4) and 63% attended > or =
      5 days per week. Seventy-six percent had > or = 1 chronic disease. Only 53%
      reported having a usual source of care, which included hospital-based clinics
      (45%), the MMTP (23%), private physicians (19%), other sites (13%). Patients were
      more likely to identify the MMTP as their usual source of care if they had
      cardiovascular disease (RR 6.9, 95% CI 2.2 to 21.9) or HIV (RR 5.6, 95% CI 1.7 to
      18.5). Successfully promoting appropriate utilization of onsite primary care may
      require a better understanding of MMTP patients' perceptions of primary care.

PMID- 17439866
TI  - Relationship of depression to smoking outcomes in a methadone-maintained
      population.
AB  - The association of depression and successful smoking cessation efforts is
      inconsistent. We test the hypothesis that higher levels of depression complicate
      efforts to quit smoking in a methadone-maintained (MM) population offered
      nicotine replacement and a brief behavioral intervention. We recruited 383
      participants from 2/02 to 5/04; 340 (88.8%) were assessed at follow- up. Current
      depressive symptoms were measured using the Psychiatric Diagnostic Screening
      Questionnaire (PDSQ). Participants were 53% male, 78% Caucasian, with a mean MM
      duration of 153 weeks. Twenty-seven percent met PDSQ screening criteria for Major
      Depressive Disorder (MDD). Participants with higher levels of depressive symptoms
      were significantly less likely to set a quit date (p = .02) but depression was
      not associated significantly with motivation to quit smoking at baseline, time to
      first cigarette, or any behavioral indicator of smoking during the follow-up
      period. Depressive symptoms have little influence on smoking cessation outcomes
      in this population.

PMID- 17439867
TI  - Controlled-release oxycodone admissions in public and private substance abuse
      treatment: associations with organizational characteristics.
AB  - Although non-medical use of controlled-release (CR) oxycodone is increasing,
      little is known about the substance abuse treatment facilities serving
      individuals dependent on this medication. This study examines the associations
      between the characteristics of treatment organizations and two dependent
      variables: any CR-oxycodone admissions and the number of CR-oxycodone admissions
      in the past six months. Face-to-face interviews were conducted with
      administrators of 363 publicly funded and 401 privately funded treatment centers
      in the US. Publicly funded non-profit organizations were less likely to have
      treated this population than government- owned, privately funded non-profit, and
      for-profit treatment centers. Some evidence indicated the availability of
      pharmacotherapies and detoxification services were associated with the dependent
      variables. Twelve-step programs were more likely to have treated oxycodone
      dependent clients. Rural facilities treated significantly more clients than those
      in metropolitan areas. The high prevalence of CR-oxycodone admissions suggests
      the need for widespread training of treatment providers regarding treatment for
      CR-oxycodone dependence.

PMID- 17439868
TI  - Predicting long-term stable recovery from heroin addiction: findings from a 33
      year follow-up study.
AB  - Heroin addiction is increasingly being recognized as a chronic relapsing
      condition, but relatively little is known about long-term recovery processes
      among addicts who attain and maintain long periods of abstinence. This study is
      to identify predictors of long-term stable recovery from heroin addiction based
      on 242 heroin addicts that have been followed for more than 30 years. Results
      showed that recovery and non-recovery groups did not differ in deviant behaviors
      and family/school problems in their earlier lives. Both groups tried formal
      treatment and self-directed recovery ("self-treatment"), often many times. While
      the non-recovered addicts were significantly more likely to use substances in
      coping with stressful conditions, to have spouses who also abused drugs, and to
      lack non-drug-using social support, stable recovery ten years later was predicted
      only by ethnicity, self-efficacy, and psychological distress. These findings
      suggest that in addition to early intervention to curtail heroin addiction,
      increasing self-efficacy and addressing psychological problems are likely to
      enhance the odds of maintaining long-term stable recovery.

PMID- 17439869
TI  - Alcohol and cocaine use and abuse among opioid addicts engaged in a methadone
      maintenance treatment program.
AB  - Alcohol and cocaine abuse result in unsatisfactory treatment outcomes for heroin
      and illicit opioid addicts engaged in Methadone Maintenance Treatment Programs
      (MMTPs). This study aims to clarify the impact of MMT, which focuses on cessation
      of opioid abuse and diminishing psychopathology to acceptable levels
      (stabilization) on alcohol and cocaine abuse. Of specific interest was whether
      reduction of polysubstance abuse and associated psychopathological complications
      diminished illicit opioid abuse and/or increased retention in treatment. Changes
      in cocaine and alcohol use that occurred in 53 heroin addicts who had been
      stabilized were monitored. A control group was composed of patients terminated
      from treatment due to noncompliance with treatment recommendations, poor
      attendance, or failure to have opioid abuse stabilized, within a year. The
      association of psychiatric severity with alcohol and cocaine abuse in these
      methadone maintained patients was assessed. Cessation of illicit opioid abuse and
      retention in treatment are positively correlated with decrease in alcohol and
      cocaine abuse and the absence of the psychosocial complications associated with
      such abuse.

PMID- 17439871
TI  - The impact of gender, depression, and personality on craving.
AB  - Craving plays an important role in the addictive behavior process. The impact of
      gender, emotional state and personality on craving, however, has been
      understudied. Ninety-six women and 86 men seeking treatment for substance
      dependence were investigated regarding the association between personality
      factors (assessed by the Temperament and Character Inventory), depressive/anxiety
      symptomatology (assessed by the Beck Depression Inventory and the Beck Anxiety
      Inventory), and craving intensity (rated in the 7-day and the 24-hour periods
      prior to assessment). Recency of substance use and impulsivity were significantly
      associated with craving intensity for both women and men. Regression analyses
      revealed that depression best predicted craving for women, but not for men. These
      results suggest that while recent substance use and impulsivity can be important
      predictors of craving across gender, depression plays a critical role in craving
      among women. This finding underscores the need for vigorous assessment and
      treatment of comorbid symptomatology in women entering addiction treatment.

PMID- 17439870
TI  - Risk of psychoactive substance dependence among substance users in a trauma
      inpatient population.
AB  - One measure of a substance's addictive risk is the proportion of users who become
      dependent. This study evaluates the lifetime and current risk of substance
      dependence among lifetime substance users' among trauma inpatients and provides a
      relative ranking of addictive risk among the substances. Data on use of 8
      substance groups (alcohol, opiates, marijuana, cocaine, other stimulants,
      sedative-hypnotics, hallucinogens, other drugs) were obtained by interview
      (Structured Clinical Interview for the DSM-III-R) from 1,118 adult trauma
      inpatients. Prevalence of lifetime dependence among lifetime users ranged from
      80.7% for opiates and 70.9% for cocaine to 33.3% for hallucinogens and 26.6% for
      sedative-hypnotics. The rank order of addictive risk was similar to that found in
      the general population. Trauma inpatients had a higher absolute addictive risk
      than the general population, comparable to the risk found in patients in
      treatment for substance use disorders, suggesting the importance of screening
      trauma inpatients for substance dependence.

PMID- 17439873
TI  - "No secrets" and beyond: recent elder abuse policy in England.
AB  - This paper provides an overview of English elder abuse policy including
      guidelines developed for adult protection by their Department of Health in 2000,
      a report released from the House of Commons Health Committee in 2004 on elder
      abuse, related policy changes affecting older adults, the mentally incapacitated,
      and social care regulations, and the launching of public awareness campaigns. In
      contrast to the U.S., English policy subsumes elder abuse within the larger
      category of vulnerable adult protection, steers clear of mandatory reporting,
      emphasizes abuse by formal caregivers rather than domestic violence, relies on a
      multi-agency approach to investigation and intervention, and supports more
      remedial, less punitive regulatory oversight.

PMID- 17439874
TI  - Nursing home statutes: mistreatment definitions.
AB  - INTRODUCTION: Forty-nine states and the District of Columbia have adult
      protective services (APS) related statutes that define adult/elder mistreatment
      found in domestic settings. Institutional adult/elder mistreatment laws are
      administered by the nursing home licensing agencies and may contain different or
      duplicate APS-related mistreatment definitions. The purposes of this paper are to
      describe and summarize the mistreatment definitions in the nursing home licensure
      statutes and compare those definitions with the definitions found in the APS
      related statutes. METHODS: Westlaw and Lexis-Nexis law database systems were used
      to retrieve all adult protective services statutes and institutional licensure
      statutes. Each statute's text was reviewed and coded by two researchers. RESULTS:
      Institutional mistreatment definitions are addressed in 14 of the states and
      District of Columbia's nursing home statutes. No one state has a list of the 27
      different definitions of mistreatment identified in the literature search. The
      common types of mistreatment described were physical and emotional abuse,
      neglect, financial and property exploitation, and sexual abuse. CONCLUSION:
      Standardized definitions of resident-to-resident and institutional specific types
      of mistreatment need to be included in nursing home statutes.

PMID- 17439875
TI  - Recommendations for the elder abuse, health, and justice fields about medical
      forensic issues related to elder abuse and neglect.
AB  - Increased interest in pursuing criminal and civil actions against alleged
      perpetrators of elder abuse and neglect has revealed that efforts to assist
      victims and hold perpetrators accountable are often hampered by the lack of
      knowledge about the detection and diagnosis of elder abuse and neglect and by the
      lack of resources for development of research and assistance in these matters.
      This report sets forth recommendations for the elder abuse, health, and justice
      fields about medical forensic issues related to elder abuse and neglect. The
      recommendations were developed by a "working group" of experts representing an
      array of disciplines that address the problem of elder abuse and neglect pursuant
      to a grant project funded by the National Institute of Justice (NIJ), the
      research, development, and evaluation agency of the U.S. Department of Justice
      (DOJ). The project was conducted by the American Bar Association Commission on
      Law and Aging, with the assistance of the University of California, Irvine School
      of Medicine. This was the final project report submitted to NIJ; it has been
      updated to include information about the availability of reports and products
      from other grant projects that are discussed in the report.

PMID- 17439876
TI  - The prevalence and incidence of intimate partner and interpersonal mistreatment
      in older women in primary care offices.
AB  - Self-report information about mistreatment experiences and perpetrators were
      collected from a large sample of women over 55 years of age who sought care from
      Midwestern primary care offices. A significantly larger proportion of women had
      experienced sexual mistreatment since turning 55 that was perpetrated by an
      intimate partner than committed by an interpersonal perpetrator. The women
      experienced significantly more threats, physical mistreatment, and caregiver
      mistreatment since turning 55, and more threats and caregiver mistreatment within
      the last year by an interpersonal perpetrator than by an intimate partner.
      Several women described different types of perpetrators who had threatened or
      mistreated them. Few women reported the mistreatment to anyone. Implications for
      elder service providers and advocates are discussed.

PMID- 17439877
TI  - Elder abuse in Europe: an overview of recent developments.
AB  - Elder abuse is a global phenomenon. Despite recognition and action several
      decades ago in a number of countries, in many others the phenomena of abuse and
      neglect have been much more recently identified as in need of attention. This
      brief will discuss the situation relating to responses to and interventions in
      elder abuse that have been evolving in a number of countries in the European
      region, which are at different stages of development. The examples provided will
      assist in meeting the worldwide challenge that elder abuse presents.

PMID- 17439878
TI  - Stress regulation in multiple sclerosis: current issues and concepts.
AB  - Since its first description by Charcot, psychological stress has been considered
      a triggering factor for exacerbations in multiple sclerosis, but until recently
      the clinical evidence for a causal relation was weak. Over the past years, a
      growing number of studies have started to elucidate this association and
      highlight potential mechanisms, including brain-immune communication. On 5 June
      2005, a panel of international researchers discussed the current evidence. This
      article summarizes the observational, animal experimental, as well as human
      experimental findings on stress regulation in MS, as well as studies on the
      functioning of the major stress response systems, ie, the hypothalamo-pituitary
      adrenal (HPA) axis and the autonomous nervous system (ANS) in MS. Consensus
      statements from the group to these aspects are given. Research objectives and
      strategies are delineated, as well as clinical implications.

PMID- 17439879
TI  - Increased CD8+ central memory T cells in patients with multiple sclerosis.
AB  - A T-cell-mediated autoimmune process against central nervous system myelin is
      believed to underlie the pathogenesis of multiple sclerosis (MS). Formation of
      immunological memory is based on the differentiation of naive T cells to memory T
      cells after exposure to antigens and specific cytokines. The aim of this study
      was to analyse peripheral blood mononuclear cells in patients with MS for
      different T-cell subsets including naive and memory T cells. Flow cytometry and
      enzyme-linked immunosorbent assay were used to analyse memory T-cell subsets and
      plasma concentration of interleukin-15 (IL-15) in peripheral blood of MS
      patients, patients with other neurological disorders and healthy controls. MS
      patients had a skewed distribution of T cells with an increased level of
      CD8+/CCR7+/CD45RA - central memory T cells (TCM) compared to healthy controls. In
      addition, MS patients showed significantly higher levels of plasma IL-15 than
      healthy controls did. Upregulated CD8+ TCM in MS patients may reflect a
      persistent chronic inflammatory response that may have been induced during early
      stages of the disease. This derangement may be important for maintaining chronic
      inflammation in MS.

PMID- 17439880
TI  - No evidence for association of CTLA-4 gene polymorphisms with the risk of
      developing multiple sclerosis: a meta-analysis.
AB  - We conducted a meta-analysis concerning the association of cytotoxic T lymphocyte
      associated antigen 4 (CTLA-4) gene polymorphisms with the risk of developing
      multiple sclerosis (MS). We identified 18 eligible studies summarizing
      information about 3375 MS cases and 2930 healthy controls. Two polymorphisms were
      of interest: the exon 1 +49 A/G polymorphism (in 18 studies) and the promoter-318
      C/T polymorphism (in 10 studies). Using random-effects methods we found no
      evidence for association of the various contrasts of genotypes (or allele
      frequencies) with the disease. There was significant between-studies
      heterogeneity that could not be explained by the ethnicity of the populations
      studied or by other summary measures (gender, disease course, latitude). The
      major finding of the meta-analysis, apart from the lack of an overall
      association, consists of detecting a significant time trend of the OR for the
      contrast of GA versus GG+AA genotypes of the exon 1 +49 A/G polymorphism. In
      particular, using cumulative meta-analysis we found that the large number of
      conflicting results on the subject was triggered by the early appearance of a
      highly significant published result (a study that indicated a significant
      association of the genotype with the disease).

PMID- 17439881
TI  - Normal-appearing grey and white matter T1 abnormality in early relapsing
      remitting multiple sclerosis: a longitudinal study.
AB  - OBJECTIVE: To investigate the presence and evolution of T(1) relaxation time
      abnormalities in normal-appearing white matter (NAWM) and grey matter (GM), early
      in the course of relapsing-remitting multiple sclerosis (MS). METHODS: Twenty
      three patients with early relapsing-remitting MS and 14 healthy controls were
      imaged six monthly for up to three years. Mean follow-up was 26 months for MS
      patients and 24 months for controls. Dual-echo fast-spin echo and gradient-echo
      proton-density and T(1)-weighted data sets (permitting the calculation of a T(1)
      map) were acquired in all subjects. GM and NAWM T(1) histograms were produced and
      a hierarchical regression model was used to investigate changes in T(1) over
      time. RESULTS: At baseline, significant patient-control differences were seen,
      both in NAWM (P <0.001) and in GM (P =0.01). At follow-up, there was no evidence
      for a serial change in either mean T(1) or peak-location for either NAWM or GM.
      There was weak evidence for a decline in patient NAWM peak-height and also
      evidence for a decline in control GM peak-height. CONCLUSION: There are
      significant and persistent abnormalities of NAWM and GM T(1) in early relapsing
      remitting MS. Further studies should address whether such T(1) measures have a
      role in prognosis or therapeutic monitoring.

PMID- 17439882
TI  - Relationship of triple dose contrast enhanced lesions with clinical measures and
      brain atrophy in early relapsing-remitting multiple sclerosis: a two-year
      longitudinal study.
AB  - Gadolinium (Gd) enhancement of lesions indicates inflammatory lesion activity in
      multiple sclerosis (MS). The question arises whether early inflammatory lesion
      activity--measured sensitively using triple dose Gd--is related to the future
      clinical course, or to the development of brain atrophy that is thought to
      reflect the underlying pathological progression of the disease. In this study, 26
      patients with early relapsing-remitting (RR) MS (median disease duration: 1.7
      years) were followed up over two years. Associations were explored between their
      levels of Gd-lesion enhancement in the first six months and later clinical
      (Expanded Disability Status Scale (EDSS) and MS Functional Composite Score
      (MSFC)) and magnetic resonance imaging (MRI) (brain volume, T(2) and T(1) lesion
      volumes) measures. The extent of Gd-enhancement in the first six months
      correlated weakly with concurrent relapses (P =0.041), but there was no
      consistent correlation with clinical and MRI outcomes at two years. More
      prolonged follow-up is warranted to clarify the relationship between early
      inflammatory lesions and long-term clinical course.

PMID- 17439883
TI  - Brain magnetic resonance imaging findings in relapsing neuromyelitis optica.
AB  - BACKGROUND: Some studies showed abnormalities in brain magnetic resonance imaging
      (MRI) of relapsing neuromyelitis optica (R-NMO) from 12 to 46%. These
      abnormalities are described as compatible/non-compatible with multiple sclerosis
      (MS). OBJECTIVE: To describe the abnormal brain MRI lesions in R-NMO with imaging
      studies conducted with more sensitive white matter change techniques. METHODS:
      Thirty patients with R-NMO were selected. All MRI brain studies were performed
      with a 1.5-T Siemens MRI system according to the Standardized MR Imaging Protocol
      for Multiple Sclerosis from the Consortium of MS Centers Consensus Guidelines.
      RESULTS: Brain MRI images were evaluated in 29 R-NMO cases because in one case
      the MRI images were not appropriate for the study. Of these 29 brain MRI studies,
      19 cases (65.5%) had at least one or more lesions (1-57) and 10 were negative
      (34.4%). Brain MRI findings in 19 cases were characterized in T2/fluid-attenuated
      inversion-recovery (FLAIR) by the presence of subcortical/deep white matter
      lesions in 16 (84.2%) cases (1-50), most of them <3 mm and without juxtacortical
      localization. Periventricular lesions were observed in 13 (68.4%) cases, but
      morphologically they were not oval, ovoid or perpendicularly orientated.
      Infratentorial lesions, all >3 mm, were observed in 4 (21.05%) cases without
      cerebellar involvement. T1 studies demonstrated absence of hypointense regions.
      Optic nerve enhancement was observed in 6/19 patients (31.5%). None of the brain
      MRI abnormalities observed were compatible with Barkhof et al. criteria of MS.
      CONCLUSIONS: This study, based on a Cuban patient population, with long duration
      of disease, good sample size and detailed characterization by MRI, demonstrated
      the brain MRI pattern of R-NMO patients, which is different from MS.

PMID- 17439884
TI  - Vestibular click-evoked myogenic potentials: sensitivity and factors determining
      abnormality in patients with multiple sclerosis.
AB  - Vestibular evoked myogenic potential (VEMP) assesses the sacculo-spinal pathway.
      The aim of our study was to examine sensitivity and factors determining
      abnormality of VEMP, indicative of brainstem dysfunction, in patients with
      multiple sclerosis (MS). Thirty healthy subjects and 30 MS patients were
      examined. All healthy subjects showed a normal biphasic response. Twelve of the
      30 MS patients (40%) had abnormal recordings. There was a significant difference
      between MS patients and control subjects with respect to P13 latency (longer in
      the MS group) and P13-N23 amplitude (lower in the MS group). VEMP abnormalities
      were statistically significantly related to the presence of brainstem
      demyelinative lesions and a weaker correlation was found with disease duration.
      Clinical signs of vestibular dysfunction at any point during the course of the
      disease did not seem to affect the chances of obtaining abnormal VEMPs. Although
      the sensitivity of VEMP in detecting abnormality in MS patients is relatively
      low, its significance is evident in that it is the only electrophysiological
      method that is able to detect dysfunction in central vestibular pathways.

PMID- 17439885
TI  - A three-dimensional approach for understanding the spectrum of idiopathic
      inflammatory demyelinating disorders: importance of the 'attack-related severity'
      axis.
AB  - Understanding the spectrum of idiopathic inflammatory demyelinating disorders
      (IIDD) of the central nervous system is an important issue for accurate diagnosis
      and advancing research on the pathogenesis as well as treatment strategies, but
      the nosology and the classification of the IIDD remains confusing. Until now, we
      have tried to apply each disorder within the spectrum to an adequate co-ordinate
      on a two-dimensional plane. One axis is clinical course and the other is lesion
      distribution. We reviewed some disorders of the IIDD spectrum, and our recent
      findings on the fulminant nature of each attack and the expansion of each lesion,
      which we called attack-related severity in Japanese multiple sclerosis (MS). From
      our findings and the literature, attack-related severity appears to be a third
      important factor, in addition to lesion distribution and clinical course.
      Introduction of the third axis produces a three-dimensional space for a better
      understanding of the heterogeneous characteristics of IIDD and 'MS' syndrome, and
      can advance treatment strategies for these disorders. As severe attacks seem to
      be relatively common in Asians but rare in the west, ethnic-related heterogeneity
      should be considered in understanding the spectrum of IIDD, and there is an
      urgent need to develop a common general concept of the spectrum, especially for
      MS.

PMID- 17439886
TI  - Interferon beta preparations for the treatment of multiple sclerosis patients
      differ in neutralizing antibody seroprevalence and immunogenicity.
AB  - Development of neutralizing antibodies (NAbs) reduces the clinical efficacy of
      interferon beta (IFNbeta) treatment in multiple sclerosis (MS) patients. The aim
      of this study was to evaluate NAb seroprevalence (frequency of patients with
      NAbs) and immunogenicity (titer levels) of IFNbeta preparations in a clinical
      setting. We analysed 1115 consecutive MS patients, treated with one of the three
      available IFNbeta preparations, for an average of 40 months (1-120 months), for
      the presence of NAbs with the MxA protein induction assay. Overall, 32% of
      patients were positive for NAbs with neutralizing titers above 10. The frequency
      of NAbs, ie, the seroprevalence, was 13% in Avonex-treated patients, 43% for
      Betaferon, 39% for Rebif22 and 30% for Rebif44. In addition, the potential to
      induce high titer levels, ie, the immunogenicity, was observed to differ between
      preparations. Avonex, showing the lowest seroprevalence, also showed low
      immunogenicity and typically induced low titers. Betaferon, showing the highest
      seroprevalence when inducing NAbs, induced lower titers compared to Rebif22 and
      Rebif44. Treatment duration over five years only marginally correlated with
      decreased seroprevalence and titer levels. In conclusion, NAbs to IFNbeta are
      common in a clinical setting and the IFNbeta preparations differ not only in NAb
      seroprevalence, but also in immunogenicity.

PMID- 17439887
TI  - Screening for depression among patients with multiple sclerosis: two questions
      may be enough.
AB  - BACKGROUND: Depression among patients with multiple sclerosis (MS) is common and
      has a significant impact on quality of life. As many as two-thirds of depressed
      MS patients receive no treatment for their depression. While guidelines for
      depression management suggest screening, the only validated screening tools are
      questionnaires, which have not been widely implemented in practice. This is the
      first study on the effectiveness of using two questions assessing mood and
      anhedonia (loss of interest or pleasure) in screening for major depressive
      disorder (MDD) in MS. METHODS: MS patients under the care of neurologists were
      recruited from a large health maintenance organization (HMO). The MDD module of
      the Structured Clinical Interview for the DSM-IV and screening questions was
      administered. RESULTS: Of the 260 participants, 26% met the criteria for MDD.
      Among patients with MDD, 67% received no anti-depressant medication. The MDD
      screen identified 99% (95% CI: 91-100%) of cases. DISCUSSION: A brief, two
      question screen is reliable in identifying MS patients with MDD. This suggests
      that asking these two brief questions could identify almost all MS patients
      meeting MDD criteria, with minimal numbers of false positives.

PMID- 17439888
TI  - Walking capacities in multiple sclerosis measured by global positioning system
      odometer.
AB  - We used a global positioning satellite technology odometer to determine the
      maximum objective walking distance capacity (MOWD) of patients with multiple
      sclerosis (MS). The MOWD correlated with Expanded Disability Status Scale (EDSS)
      score (r(2) =0.41; P <0.0001), the MSWS-12 scale (r(2) =0.46; P <0.0001), time to
      walk 10 m (r(2) =0.51; P <0.02) and walking speed (r(2) =0.75; P <0.001).
      Limitation of walking capacities was measurable up to 4550 m, strikingly above
      the 500-m limit of the EDSS. This objective odometer is a promising tool for
      evaluation and follow-up of patients with MS.

PMID- 17439889
TI  - Advanced lightweight cooling-garment technology: functional improvements in
      thermosensitive patients with multiple sclerosis.
AB  - Cooling of thermosensitive patients with multiple sclerosis (MS) can improve
      clinical symptoms. In order to study the effectiveness of an advanced lightweight
      cooling-garment technology based on aquatic evaporation, a single-blinded
      balanced crossover study was performed on 20 patients with an Expanded Disability
      Status Scale score < or =6.5. The results using a tight-cuff cooling-garment
      prototype for peripheral cooling suggest improvement of a timed-walking test, leg
      strength, fine-motor skills and subjective benefits. Preliminary data of the
      heart rate variability (HRV) including six patients suggest that the MS patients
      show an abnormal HRV after sham condition, which is normalized after cooling.
      Technical information was gained about the cooling activity and the
      practicability and handling of the device. These encouraging findings promote
      further adaptations of the prototype to increase its cooling properties and
      ameliorate the practicability of the cooling garment.

PMID- 17439890
TI  - Predictors of well-being among significant others of persons with multiple
      sclerosis.
AB  - OBJECTIVE: To examine patient and significant other characteristics as predictors
      of significant other well-being. METHODS: A total of 74 persons with multiple
      sclerosis (MS) and their significant others participated. Executive functioning
      was measured using neuropsychological tests. Awareness of cognitive deficit was
      measured as the discrepancy between the patient's reports of their abilities and
      objective test results. Awareness of functional deficit was measured as the
      discrepancy between the patient's and significant other's reports of the
      patient's functional abilities. Patient neurobehavioral disturbance was measured
      using a significant-other rated questionnaire. Significant other perceived social
      support and well-being (ie, psychological distress, life satisfaction, and
      general health status) were assessed using questionnaires filled out by the
      significant other. RESULTS: Executive dysfunction, neurobehavioral disturbance,
      and lack of awareness of functional deficits in patients were associated with
      poor well-being outcomes; whereas, lack of awareness of cognitive deficits was
      only weakly related to well-being. Social support was associated with positive
      well-being outcomes. CONCLUSIONS: Diminished insight regarding functional
      limitations may increase significant others' supervisory burden as patients
      attempt activities independently, whereas lack of awareness of cognitive deficits
      may not be directly associated with behavior-relevant impairments that
      significant others find distressing. Social support appears to be a powerful aid
      in diffusing the distress among significant others of MS patients.

PMID- 17439891
TI  - The 795CT polymorphism in osteopontin gene is not associated with multiple
      sclerosis in a Spanish population.
AB  - Multiple sclerosis (MS) is an inflammatory disease affecting the central nervous
      system. The dysregulation of the cytokine network is an important component of
      its pathogenesis. One of the cytokines produced by activated T-cells is
      osteopontin (OPN). OPN enhances the production of the pro-inflammatory cytokines,
      interleukin-12 and interferon-gamma, while reducing interleukin-10 levels.
      Therefore, OPN is considered a pro-inflammatory cytokine, and could play a key
      role in MS pathogenesis. The OPN gene contains several common polymorphisms,
      distributed in two main haplotypes, which may modulate its production or
      activity. A total of 326 MS patients and 484 healthy controls were typed for
      795CT OPN polymorphism. In order to perform a familial study, 51 progenitor pairs
      were also included. No difference was found in the case-control or family study.
      This negative finding is inconsistent with a previous haplotype study in an
      Italian population, where the haplotype associated carried the low-frequency
      allele in position 795. In a Japanese population, a similar study yielded no
      association with this polymorphism. In conclusion, our data suggest that the 795
      polymorphism does not play an etiological role per se and the haplotype structure
      may differ from one population to another.

PMID- 17439892
TI  - Profile of cytokine gene polymorphisms in Iranian multiple sclerosis patients.
AB  - BACKGROUND: Cytokine gene polymorphisms have been extensively studied in
      association with different diseases. The role of cytokine gene polymorphisms in
      multiple sclerosis (MS), as a chronic immune-mediated neurodegenerative disease,
      has been previously reported. MATERIALS AND METHODS: DNA samples were collected
      from 44 patients with relapsing-remitting multiple sclerosis (RRMS) and 140
      unrelated healthy subjects. All participants in this study were matched for
      ethnicity. Cytokine gene SNPs were determined using the PCR-SSP method. RESULTS:
      and discussion We found no significant differences between MS patients and
      controls in most of the studied cytokine genes. Remarkable results were obtained
      for IL-2 GG-330 genotype (P =0.06), IL-6 C-174 allele (P =0.06), CG and GG
      genotypes (P <0.001), and GG (P =0.02) and CG (P <0.001) haplotypes, and TNF
      alpha A-238 allele (P <0.001), GG (P =0.003) and GA (P <0.001) haplotypes. These
      results suggest that polymorphic variations of these pro-inflammatory cytokines
      play an important role in susceptibility to MS.

PMID- 17439893
TI  - Immunosuppressive therapy is more effective than interferon in neuromyelitis
      optica.
AB  - To determine long-term treatment (LTT) of neuromyelitis optica (NMO), we
      retrospectively reviewed therapies of 26 patients with NMO followed in five
      French neurological departments. To assess LTT efficacy, the probability of
      relapse free after LTT was analysed. Patients were divided into two groups
      according to the first treatment receiving interferon beta (IFN Group, seven
      patients) or immunosuppressants (IS Group, 19 patients). The probability of
      relapse was significantly lower in the IS Group (P =0.0007). From our results,
      interferon beta is not recommended, and one of the best current therapeutic
      options for NMO appears to be immunosuppressants.

PMID- 17439894
TI  - Epidemiology of familial multiple sclerosis in Hungary.
AB  - The prevalence of familial aggregation of multiple sclerosis (MS) is estimated
      between 5 and 10%. Studies emphasize the effect of genetic factors over the
      environment of the patients in the development of the disease. We investigated
      familial accumulation of MS in the cases of 1500 patients in five Hungarian MS
      centers. According to our data, the risk of familial MS in Hungary is lower than
      in other countries for which literature data are accessible. The literature does
      not contain any data for the prevalence of familial MS in Hungary and middle
      eastern Europe.

PMID- 17439895
TI  - Prevalence of multiple sclerosis in Santiago de Compostela (Galicia, Spain).
AB  - INTRODUCTION: Multiple sclerosis (MS) is the most common central nervous system
      disease in young adults, and one of the leading causes of disability in this age
      group. OBJECTIVES: To establish the prevalence and incidence of MS in Santiago de
      Compostela (Spain). Material and methods We performed a prospective, case-finding
      study on > 90,188 inhabitants, from 1 January 1998 to 15 September 2003, selected
      as day of prevalence. Sources of information were the University Clinical
      Hospital of Santiago, the hospitals and private clinics of the city,
      rehabilitators, pediatricians, ophthalmologists, psychiatrists, neurosurgeons,
      specialists in internal medicine, primary care physicians, association of
      patients of MS, social services and nongovernmental and religious associations.
      Informative days were programmed for the susceptible population, and campaigns
      were carried out in the media. All patients with Poser diagnostic criteria for
      MS, on the census of Santiago de Compostela as of 15 September 2003, were
      included in the study. RESULTS: On the day of prevalence, 71 patients with MS
      were registered on the census of Santiago de Compostela, therefore, the
      prevalence was 79 cases per 100,000 inhabitants. The incidence of the disease in
      the study period was 5.3 cases per 100,000 inhabitants and year. CONCLUSIONS: The
      prevalence and incidence rates of MS found in Santiago de Compostela are the
      highest reported, to date, in Spain.

PMID- 17439896
TI  - A longitudinal conventional and magnetization transfer magnetic resonance imaging
      study of optic neuritis.
AB  - Eleven consecutive patients with a first episode of acute optic neuritis were
      evaluated, using conventional and magnetization transfer (MT) magnetic resonance
      imaging (MRI), in order to assess the temporal evolution of optic nerve (ON)
      damage and to investigate the correlation of ON damage with visual outcome and
      electrophysiological parameters. Patients underwent neuroophthalmological,
      neurological, electrophysiological, and MRI assessments at baseline and after
      three and 12 months. ON volumes were measured on coronal T1-weighted images using
      a local thresholding segmentation technique. MT ratio (MTR) from the ON was
      derived from gradient echo images. No significant volume difference was detected
      between affected and healthy ON, both at baseline and follow-up. At baseline,
      mean MTR values were significantly higher in affected ON than in healthy ON (P
      =0.001), whereas at months 3 and 12, the mean MTR values were significantly
      reduced in the affected ON (P =0.02 and 0.003, respectively). Mean MTR of the
      affected ON, corrected for healthy ON values, progressively decreased over time
      (P =0.04 at month 3 and P =0.0012 at month 12). On the contrary, MTR values of
      healthy ON remained stable. No correlations were found between MTR measures and
      clinical or electrophysiological data. This study shows the presence of subtle
      pathological changes, possibly due to residual demyelination and subsequent
      additional demyelination and impaired remyelination, in the ON of patients with a
      first episode of optic neuritis. In the early phase of optic neuritis, MT MRI is
      more sensitive than atrophy measurements in detecting disease-related changes.

PMID- 17439897
TI  - Effects of motor cortex rTMS on lower urinary tract dysfunction in multiple
      sclerosis.
AB  - We tested the effects of 5-Hz rTMS over the motor cortex in multiple sclerosis
      (MS) subjects complaining of lower urinary tract symptoms either in the filling
      or voiding phase. Our data show that motor cortex stimulation for five
      consecutive days over two weeks ameliorates the voiding phase of the micturition
      cycle, suggesting that enhancing corticospinal tract excitability might be useful
      to ameliorate detrusor contraction and/or urethral sphincter relaxation in MS
      patients with bladder dysfunction.

PMID- 17439898
TI  - Rapid cognitive screening in multiple sclerosis accomplished by the Free Recall
      and Recognition Test.
AB  - This study sought to investigate the feasibility of the Free Recall and
      Recognition Test (FRRT) as a practical screening tool for cognitive impairment in
      multiple sclerosis (MS). Persons with MS (n = 227) were consecutively recruited
      and assessed with four cognitive tests; FRRT, Symbol Digit Modalities Test
      (SDMT), Paced Auditory Serial Addition Test (PASAT), and the Mini-Mental State
      Examination (MMSE). Disease severity was assessed by the Expanded Disability
      Status Scale (EDSS). The FRRT, which was completed by 99% of the cohort in
      approximately 5 minutes per assessment, correlated significantly with the other
      cognitive tests, as well as with the disease severity rating. A cut-off of 4 for
      the FRRT recall rendered 90% sensitivity and 25% specificity, and a cut-off of
      4.2 for the FRRT recognition resulted in 70% sensitivity and 51% specificity. We
      conclude that the FRRT proved feasible as a practical screening tool for
      cognitive impairment in MS within a clinical setting.

PMID- 17439899
TI  - Impact of depression and disability on quality of life in Iranian patients with
      multiple sclerosis.
AB  - Multiple sclerosis (MS) can influence all aspects of a patient's health. This
      study determines the main factors affecting quality of life (QoL) in Iranian MS
      patients. QoL (Multiple Sclerosis Impact Scale; MSIS-29), disability (Expanded
      Disability Status Scale; EDSS) and depression (Beck Depression Inventory; BDI)
      were assessed in 106 MS patients. EDSS, clinical course and MS duration
      significantly correlated with physical MSIS-29. Depression highly correlated with
      both physical and psychological MSIS-29. Regression analyses showed that
      depression and EDSS predicted physical health. Psychological health was predicted
      by depression. These findings highlight that depression and physical disability
      strongly influence QoL in Iranian MS patients.

PMID- 17439900
TI  - Production of brain-derived neurotrophic factor by mononuclear cells of patients
      with multiple sclerosis treated with glatiramer acetate, interferon-beta 1a, and
      high doses of immunoglobulins.
AB  - Sixty, relapsing remitting (RR) multiple sclerosis (MS) patients, who underwent
      treatment with glatiramer acetate (GA), interferon (IFN)-beta 1a, and
      immunoglobulins (Igs) (20 per treatment group), were assessed for levels of brain
      derived neurotrophic factor (BDNF) in the supernatants of unstimulated and
      stimulated peripheral blood mononuclear cells (PBMCs) in the first year of
      treatment. Phytohemagglutinin (PHA), anti-OKT3 antibody, myelin basic protein
      (MPB) and GA were used as stimuli. Cytokine responses by ELISPOT and
      lymphoproliferative responses were also assessed. The GA-treated MS patient group
      showed a progressive increase in BDNF levels, from baseline to month three;
      thereafter, the levels remained stable and significantly greater compared with
      baseline and controls (ANOVA=P<0.001). IFN-beta 1a had no effect on BDNF
      production, whereas Igs induced a slight decrease (ANOVA=P<0.04). ELISPOT
      analysis revealed a significant decrease of IFN-gamma, an increase of interleukin
      (IL)-4 and IL-5 in GA-treated MS patients, and an increase of IL-10 in patients
      treated with IFN-beta 1a and GA. No significant correlation was found between
      BDNF secretion in the supernatants of PBMCs and cytokine response, lesional load,
      and measures of atrophy. Increased BDNF production related to GA treatment can
      have implications for understanding the mechanism of action of this
      immunomodulatory agent, in light of evidence suggesting its effects in promoting
      neuroprotective immunity in MS patients; however, a clinically measurable effect,
      especially in terms of an impact on actual disease progression, remains to be
      established.

PMID- 17439901
TI  - Clinical and laboratory features of neuromyelitis optica with oligoclonal IgG
      bands.
AB  - Of 23 neuromyelitis optica (NMO) cases, we found two cases with oligoclonal IgG
      bands (OBs). Both patients were positive for NMO-IgG. Their common features were
      long disease duration and co-existing autoimmune diseases (myasthenia gravis and
      sicca syndrome). Although OBs are mostly negative in NMO, which distinguishes it
      from multiple sclerosis (MS), they can be positive by long-standing autoimmunity,
      which may not be directly related to NMO.

PMID- 17439902
TI  - Predicting beta-interferon failure in relapsing-remitting multiple sclerosis.
AB  - Proposed beta-interferon (IFNbeta) treatment failure criteria for patients with
      relapsing-remitting multiple sclerosis (RRMS) have not been validated in clinical
      practice. This study aimed to establish (a) whether IFNbeta attenuated
      accumulation of fixed disability in comparison to a cohort of matched historical
      control subjects from the Sylvia Lawry centre for MS research, and (b) whether
      relapse-based treatment failure criteria or clinical and demographic variables
      had predictive value for the accumulation of fixed disability. Of the 175 IFNbeta
      treated RRMS patients, 60 (34%) developed accumulation of fixed disability over a
      median of five years follow-up, which was significantly less than the rate of
      accumulation of fixed disability in the control group (P<0.0001). Any relapse in
      the treatment period predicted accumulation of fixed disability with a
      sensitivity of 80% and specificity of 43%; patients totally relapse free were
      less likely to develop accumulation of fixed disability (P <0.002). Multivariate
      analysis confirmed that a greater risk of accumulation of fixed disability was
      conferred by a higher Expanded Disability Status Scale (EDSS) score starting
      IFNbeta (P=0.02), and by failure of IFNbeta to completely suppress relapses
      (P=0.004). In conclusion, IFNbeta therapy reduced the accumulation of fixed
      disability in a cohort of RRMS patients, followed for a median of five years.
      Higher baseline EDSS and failure of complete relapse suppression were associated
      with a significantly greater likelihood of accumulation of fixed disability.

PMID- 17439903
TI  - An exploratory study on interferon beta dose effect in reducing size of enhancing
      lesions in multiple sclerosis.
AB  - Sixty-two patients with multiple sclerosis (MS) were imaged monthly over a six
      month (ie, seven monthly magnetic resonance images [MRI]) natural history period
      (NHP). Thereafter, patients were randomized to receive 11 or 33 mug of
      subcutaneously injected interferon beta 1a (IFNp-1 a) with imaging monthly for
      nine months and at months 12, 18 and 24 of therapy phase (TP). In the present
      exploratory post hoc analysis, the authors evaluated IFNbeta-1a dose effect on
      reducing the size of contrast-enhancing lesions (CELs). MRIs performed at months
      0, 3 and 6 of NHP and at months 3, 6, 9, 18 and 24 of TP were analysed. While a
      significant reduction in mean number of CELs was observed in both treatment
      groups of patients, the mean total volume and size of CELs was reduced only in
      patients undergoing therapy with 33 mug of IFNbeta-1a. The latter suggests a
      significant dose effect exerted by IFNbeta-1a in the evolution of CELs'
      dimensions during therapy.

PMID- 17439904
TI  - Prospective clinical and electrophysiological follow-up on a multiple sclerosis
      population treated with interferon beta-1 a: a pilot study.
AB  - OBJECTIVE: To analyse transcranial magnetic stimulation (TMS) variables in a
      prospective six-month follow-up pilot study on patients suffering from relapsing
      remitting multiple sclerosis (RRMS), satisfying inclusion criteria for interferon
      (IFN) beta-1a treatment. BACKGROUND: So far, no predictive factors are available
      as to the course of RRMS treated with IFN beta-1 a. DESIGN/METHODS: Fifteen RRMS
      patients were studied before (month 0 (M0)) and after IFN beta-1a onset (M3, M6).
      The parameters analysed were motor functional score (mFS), Expanded Disability
      Status Scale (EDSS), and TMS variables - central motor conduction time (CMCT) and
      amplitude ratio (AR). RESULTS: Four of the six patients with no motor signs at
      inclusion, subsequently showed signs of pyramidal dysfunction. All had abnormal
      M0_TMS variables. The number of M0_TMS abnormalities per patient was greatest in
      the group that showed mFS worsening, and was significantly correlated with
      M6_EDSS. The M0_CMCT was significantly correlated with M6_EDSS. During follow-up,
      the number of patients with abnormal TMS variables decreased from 12/15 to 4/15,
      and the total number of abnormalities decreased from 33.3 to 16.7%. CONCLUSIONS:
      TMS variables might be predictive of disease progression. The improvement
      observed here in the TMS variables may reflect an improvement in MS patients
      undergoing IFN beta treatment.

PMID- 17439905
TI  - Fampridine-SR in multiple sclerosis: a randomized, double-blind, placebo
      controlled, dose-ranging study.
AB  - OBJECTIVE: To determine the safety of sustained-release 4-aminopyridine in
      subjects with mutiple sclerosis (MS) and to examine dose-related efficacy up to
      40 mg twice daily. METHOD: Multicenter, randomized, double-blind, placebo
      controlled, study. Following a 4-week baseline peroid, subjects were randomly
      assigned to receive Fampridine-SR (n=25, doses from 10 to 40 mg twice daily,
      increasing in 5 mg increments weekly) or placebo (n=11). A battery of assessments
      was performed weekly, including the MS Functional Composite (MSFC), fatigue
      questionnaires, and lower extremity manual muscle testing. RESULTS: The most
      common adverse events were dizziness, insomnia, paresthesia, asthenia, nausea,
      headache, and tremor. Five subjects were discontinued from Fampridine-SR because
      of adverse events at doses greater than 25 mg, and these included convulsions in
      two subjects at doses of 30 and 35 mg twice daily. Improvement were seen in lower
      extremity muscle strength (prospective analysis) and walking speed (post-hoc
      analysis) in the Fampridine-SR group compared to placebo (unadjusted p-values of
      0.01 and 0.03, respectively). There were no significant differences in other MSFC
      measure or fatigue scores. CONCLUSIONS: Future studies should employ doses up to
      20 mg twice daily with lower extremity strength and walking speed as potential
      outcome measures.

PMID- 17439906
TI  - Studies of associations between disability in multiple sclerosis, skin type,
      gender and ultraviolet radiation.
AB  - Recent studies suggest ultraviolet radiation (UVR)/vitamin D is protective
      against the development of multiple sclerosis (MS). We determined if outcome in
      MS is associated with the surrogate for host pigmentation, skin type, and
      parameters of UVR exposure. We used a validated questionnaire to determine skin
      type and UVR exposure during childhood (0-16 years), and early adult life (17-40
      years), in 448 Caucasians with MS. Outcome was assessed using the Kurtzke
      Expanded Disability Status Score (EDSS) and Multiple Sclerosis Severity Scale
      (MSSS). We studied the association of skin type and exposure with dichotomized
      values of EDSS (< and >or=6) and MSSS (continuous variable) using logistic and
      linear regression analyses, respectively. Sex, onset age and MS duration were
      significantly associated with outcome in all patients. In 169 females with
      established disease (>or=10 years), sun sensitive skin types 1 and 2 were
      associated with reduced risk of EDSS >or=6 (odds ratio =0.50; 95% CI = 0.26
      0.97), and higher MSSS values (coefficient = -0.86; 95% CI = -1.67 to -0.05).
      Parameters of UVR exposure were not significantly associated with outcome. These
      preliminary data show an association between skin type and disability in female
      MS patients. They are compatible with independent studies suggesting that
      exposure mediates MS pathogenesis via vitamin D. Further studies are required to
      properly assess these potentially important findings.

PMID- 17439907
TI  - Ginkgo biloba for the improvement of cognitive performance in multiple sclerosis:
      a randomized, placebo-controlled trial.
AB  - OBJECTIVES: To determine if Ginkgo biloba (GB) improves the cognitive performance
      of subjects with multiple sclerosis (MS). METHODS: Randomized, double-blind,
      placebo-controlled trial of GB, 120 mg twice a day or placebo for 12 weeks. The
      primary outcomes were: the long delay free recall from the California Verbal
      Learning Test-II; the Paced Auditory Serial Addition Test; the Controlled Oral
      Word Association Test; the Symbol Digit Modalities Test; Useful Field of View
      Test; and the color-word interference condition from the Stroop Color and Word
      Test. RESULTS: On completion, the GB group (n=20) was 4.5 seconds (95% confidence
      interval (CI) (7.6, 0.9), P=0.015) faster than the placebo group (n=18) on the
      color-word interference condition of the Stroop test. Subjects who were more
      impaired at baseline experienced more improvement with GB (treatment*baseline
      interaction, F=8.10, P=0.008). We found no differences on the other
      neuropsychological tests. Subjects on GB reported fewer cognitive difficulties in
      the Retrospective Memory Scale of the Perceived Deficits Questionnaire than
      subjects on placebo (1.5 points, 95% CI (2.6, 0.3), P=0.016). No serious drug
      related side-effects occurred and GB did not alter platelet function assays.
      CONCLUSION: Overall, GB did not show a statistically significant improvement in
      cognitive function. A treatment effect trend, limited to the Stroop test,
      suggests that GB may have an effect on cognitive domains assessed by this test,
      such as susceptibility to interference and mental flexibility.

PMID- 17439908
TI  - Health-related quality of life in secondary progressive multiple sclerosis.
AB  - Common disability scales in multiple sclerosis (MS) are often weighted towards
      physical disability. Non-motor symptoms such as depression, fatigue and pain
      substantially influence wellbeing in MS. Health-related quality of life (HRQoL)
      measures the broader impact of MS and might indicate less obvious disease
      burdens. We analysed HRQoL, using the Nottingham Health Profile Part I (NHP-I),
      among 345 secondary progressive MS (SPMS) patients participating in a randomized
      trial of interferon-beta1a (IFN-beta1a), 22 mug subcutaneously weekly, or
      matching placebo. The results did not reveal any beneficial effect of IFN-beta1a
      in any outcome measure. NHP-I sub- and sum scores were compared for 217
      population controls and correlated with demographic and clinical disease
      variables. SPMS patients had lower NHP-I sum and all subscores than the controls.
      Patients experiencing disease progression reported worse NHP-I sum scores.
      Increased fatigue, Expanded Disability Status Scale (EDSS) and Arm Index scores
      were independently associated with reduction in several NHP-I subscores. SPMS
      patients had significantly lower HRQoL than controls and physical disability
      (EDSS and Arm Index), disease progression and fatigue strongly influenced this.
      MS.

PMID- 17439909
TI  - Coping and quality of life in one hundred and thirty five subjects with multiple
      sclerosis.
AB  - INTRODUCTION: and objective The aim of this study was to compare coping
      strategies and quality of life (QoL) in multiple sclerosis (MS), as they relate
      to the course of the disease (relapsing-remitting (RR), secondary progressive
      (SP), primary progressive (PP)), while taking depression and anxiety into
      account. METHODS: A total of 135 MS subjects were seen for a semi-structured
      interview in order to collect socio-demographic and clinical information, after
      which there was an assessment of their mental and cognitive states (Mini
      International Neuropsychiatric Interview (MINI), Montgomery and Asberg Depression
      Rating Scale (MADRS), Depressive Mood Scale (EHD), Hamilton Anxiety (HAMA),
      Frontal Assessment Battery (FAB)). All subjects then completed three self-report
      questionnaires; two about coping strategies (Ways of Coping Checklist (WCC),
      Coping with Health, Injuries and Problems Scale (CHIP)) and one about QoL
      (SEP59). RESULTS: The mental health (depression and anxiety) and the
      psychological and social dimensions of QoL were relatively unaffected. However,
      after controlling for age and disability, the disease course had a strong effect
      on both mental health and QoL, with the poorest condition for SPMS and the best
      condition for PPMS. The SPMS patients tend to use emotional coping strategies
      extensively, while the PPMS patients use more instrumental strategies.
      DISCUSSION: Our study clearly demonstrated that psychological and social well
      being were substantially affected by the disease course. These results encourage
      us to develop interventions focused on coping strategies and which are better
      adapted to individual patients.

PMID- 17439910
TI  - The Faces Symbol Test, a newly developed screening instrument to assess cognitive
      decline related to multiple sclerosis: first results of the Berlin Multi-Centre
      FST Validation Study.
AB  - Reliable, language-independent, short screening instruments to test for cognitive
      function in patients with multiple sclerosis (MS) remain rare, despite the high
      number of patients affected by cognitive decline. We developed a new, short
      screening instrument, the Faces Symbol Test (FST), and compared its diagnostic
      test characteristics with a composite of the Digit Symbol Substitution Test
      (DSST) and the Paced Auditory Serial Addition Test (PASAT), in 108 MS patients
      and 33 healthy controls. An Informant-Report Questionnaire, a Self-Report
      Questionnaire, and a neurologist's estimation of the Every Day Life Cognitive
      Status were also applied to the MS patients. The statistical analyses comprised
      of a receiver operating characteristic analysis for test accuracy and for
      confounding variables. The PASAT and DSST composite score estimated that 36.5% of
      the MS patients had cognitive impairment. The FST estimated that 40.7% of the MS
      patients were cognitively impaired (sensitivity 84%; specificity 85%). The FST,
      DSST and PASAT results were significantly correlated with the patients' physical
      impairment, as measured by the Expanded Disability Status Scale (EDSS). The
      results suggest that the FST might be a culture-free, sensitive, and practical
      short screening instrument for the detection of cognitive decline in patients
      with MS, including those in the early stages.

PMID- 17439911
TI  - Caregiver quality of life in multiple sclerosis: a multicentre Italian study.
AB  - The purpose of this study was to evaluate the quality of life (QoL) of multiple
      sclerosis (MS) caregivers, and to determine relationships that may exist between
      caregiver and patient QoL. Patients with definite MS (n=445) and their caregivers
      (n=445) were required to complete the generic, 36-item short-form (SF-36) Health
      Survey. Median SF-36 dimension scores ranged from 55 to 100 for caregivers and
      from 46 to 78 for patients. Although the QoL of MS carers was not as severely
      affected as that of patients, caregiving was associated with lower mental health,
      vitality and general health scores, compared to healthy subjects. Multivariate
      analyses revealed significant differences between the predictors of patient QoL
      and caregiver QoL. The main predictors of patient QoL were Expanded Disability
      Status Scale (EDSS) score, MS course, fatigue and depression. Female gender and
      advanced age were the main predictors of lower QoL in caregivers. In addition,
      patient BDI score was found to be a significant predictor of almost all caregiver
      SF-36 dimension scores, while EDSS score, disease duration and course, and
      patient therapeutic characteristics were found to be predictors of some caregiver
      SF-36 dimension scores. Therefore, caregiver QoL was significantly influenced by
      patient characteristics, and supportive strategies for MS caregivers are
      warranted.

PMID- 17439912
TI  - Correlations between Epstein-Barr virus antibody levels and risk factors for
      multiple sclerosis in healthy individuals.
AB  - BACKGROUND: Female gender, human leukocyte antigen (HLA) DR2, tobacco smoking and
      Epstein-Barr virus (EBV) are established risk factors for multiple sclerosis
      (MS). Their possible interaction however, has been sparsely studied. OBJECTIVES:
      To investigate possible associations between EBV antibody levels and a range of
      other recognized MS risk factors. DESIGN, SETTING AND STUDY POPULATION: Cross
      sectional study undertaken in Denmark based on 517 healthy individuals selected
      from the Danish population. METHODS: We measured change in mean log (anti-Epstein
      Barr viral capsid antigen (VCA) immune globulin G) using linear regression.
      RESULTS: Anti-Epstein-Barr VCA immune globulin G levels were positively
      correlated with female gender and HLA DR2. Furthermore, current smoking and
      cumulative tobacco consumption were positively associated with EBV antibody
      levels. CONCLUSION: The association between Epstein-Barr VCA antibody levels and
      non-viral MS risk factors support the view that EBV is critically involved in the
      etiology of MS. These non-viral MS risk factors may be linked with MS risk
      through EBV-specific immune responses.

PMID- 17439913
TI  - Arg113His mutation of vanishing white matter is not present in multiple
      sclerosis.
AB  - Vanishing white matter (VWM) is a childhood leukoencephalopathy with central
      hypomyelination, white matter rarefaction, and cystic degeneration. Adult onset,
      variable phenotype, and high frequency characterize Arg113His mutation caused by
      G338A polymorphism associated with VWM. A patient with trauma-associated onset,
      and clinical features compatible with multiple sclerosis (MS), was homozygous for
      G338A mutation of eukaryotic translation initiation factor (eIF2B5). The authors
      checked a cohort of 101 MS patients, including 19 with head/neck trauma
      associated onset, and failed to find the mutation, described above, in MS
      chromosomes. Our report does not exclude the presence in MS chromosomes of other
      mutations in the eIF2B gene family.

PMID- 17439914
TI  - Subtle upper limb impairment in asymptomatic multiple sclerosis subjects.
AB  - We evaluated upper limb function in multiple sclerosis (MS) subjects (11
      clinically definite MS patients and seven clinically isolated syndrome (CIS)
      subjects), with a normal upper limb standard neurological examination. Subjects
      performed center-out reaching movements under visual control, with and without
      vision of the hand. Their movements were recorded through a digitizing tablet.
      Motor performance was also related to lesion load, estimated from magnetic
      resonance imaging (MRI). We found that in MS and CIS subjects, under the hand
      vision condition, movements were significantly less smooth, and had a less
      symmetric speed profile. However, the observed impairment did not correlate with
      MRI findings. This result may be interpreted as evidence of a compensatory
      strategy, elicited by subtle alterations in sensorimotor control.

PMID- 17439915
TI  - Down's syndrome and neuromyelitis optica (Devic's disease). An autopsy-proven
      case.
AB  - Neuromyelitis optica (NMO) has been attributed to different underlying
      pathological events. The aim of this paper is to present the first case report of
      a patient with Down's syndrome (DS) who died of a fulminant NMO. A 29-year-old
      woman with DS developed acute transverse myelitis, with complete visual loss and
      swollen optic discs. Two days later, she developed quadriplegia, respiratory
      arrest and died. The anatomical study demonstrated typical findings of DS in the
      brain without demyelinating lesions. A severe destruction of medulla and cervical
      cord with a very high degree of demyelination of the optic nerves was typical of
      monophasic NMO (Devic's disease). Most of the cases of NMO in Cuba are of the
      relapsing form, but this case report is the first one with monophasic NMO and DS
      with a very aggressive course. The link of the pathogenetic relationship between
      DS and NMO remains unclear; it may well be coincidence but the fact that the
      patient died very shortly after the onset suggests, at least on clinical grounds,
      that the presence of DS could have accelerated the fatal evolution of NMO.

PMID- 17439917
TI  - Trigeminally-mediated health effects of air pollutants: sources of inter
      individual variability.
AB  - Trigeminal (ocular and nasal) irritation comprises the dominant symptom complex
      in so-called "problem buildings". Imputed etiologic agents in indoor air include
      extremes of temperature and humidity, the presence of volatile organic compounds,
      combustion products (including tobacco smoke), ozone (from office machines), and
      products of indoor air chemistry. In addition to producing primary irritation,
      mucosal irritants trigger a variety of secondary reflex symptoms, such as nasal
      congestion, rhinorrhea, and sinus pressure, and may predispose to infection in
      the form of sinusitis and otitis media. Marked variability in self-reported
      sensitivity to indoor air pollutants has been observed, with females, younger
      individuals, and people with allergies reporting more symptoms. We report on a
      series of experiments designed to uncover demographic patterns of "nasal irritant
      sensitivity", as well as potential mechanism(s) involved in observed chemesthetic
      variability.

PMID- 17439918
TI  - Early lead exposure increases the leakage of the blood-cerebrospinal fluid
      barrier, in vitro.
AB  - The cell type constructing the blood-brain barrier (BBB) and blood-cerebrospinal
      fluid barrier (BCB) is entirely different, ie, endothelia in BBB and epithelia in
      BCB. Nonetheless, both barriers share a common character--the tight junctions
      (TJ) between adjacent cells. This study investigated the consequence of lead (Pb)
      exposure on the tightness of BCB. In an in vitro BCB transwell model, using
      immortalized choroidal epithelial Z310 cells, we found that early exposure to Pb
      (prior to the formation of tight barrier) at 5 and 10 microM, significantly
      reduced the tightness of BCB, as evidenced by a 20% reduction in transepithelial
      electrical resistance (TEER) values (P <0.05), and >20% increase in the
      paracellular permeability of [(14)C]sucrose (P <0.05). Exposure to Pb after the
      formation of tight barrier, however, did not cause any detectable barrier
      dysfunction. RT-PCR and Western blot analyses on typical TJ proteins revealed
      that Pb exposure decreased both the mRNA and protein levels of claudin-1, with
      the membrane-bound claudin-1 more profoundly affected than cytosolic claudin-1.
      Pb exposure, however, had no significant effect on ZO1 and occludin. These data
      suggest that Pb exposure selectively alters the cellular level of claudin-1,
      which, in turn, reduces the tightness and augments the permeability of tight
      blood-CSF barrier. The immature barrier appears to be more vulnerable to Pb
      toxicity than the mature, well-developed, brain barrier, the fact possibly
      contributing to Pb-induced neurotoxicity among young children.

PMID- 17439919
TI  - Neurosensory effects of chronic human exposure to arsenic associated with body
      burden and environmental measures.
AB  - Exposure to arsenic in drinking water is known to produce a variety of health
      problems, including peripheral neuropathy. Auditory, visual and somatosensory
      impairment have been reported in Mongolian farmers living in the Yellow River
      Valley, where drinking water is contaminated by arsenic. In the present study,
      sensory tests, including pinprick and vibration thresholds, were administered to
      320 residents with well-water arsenic levels, ranging from non-detectable to 690
      microg/L. Vibration thresholds in the second and fifth fingers of both hands were
      measured using a vibrothesiometer. Drinking water, urine and toenail samples were
      obtained to assess arsenic exposure and body burden. Regression analyses
      indicated significant associations of pinprick scores and vibration thresholds
      with all arsenic measures. Vibration thresholds were more strongly associated
      with urinary than water or nail arsenic measures, but odds ratios for decreased
      pinprick sensitivity were highest for the water arsenic measure. Results of the
      current study indicate neurosensory effects of arsenic exposure at concentrations
      well below the 1000 microg/L drinking water level specified by NRC, and suggest
      that non-carcinogenic end-points, such as vibration thresholds, are useful in the
      risk assessment of exposure to arsenic in drinking water.

PMID- 17439920
TI  - Neurobehavioral alterations in rats exposed to acrylonitrile in drinking water.
AB  - This study was carried out on rodents, to explore the neurobehavioral effects of
      acrylonitrile (AN) administered in drinking water. Thirty, male, Sprague-Dawley
      rats were randomly divided into three groups: two exposure groups (50 and 200 ppm
      AN), and one control group (tap water without AN). Three tests, including the
      open field test, rotarod test and spatial water maze, were applied to evaluate
      locomotor activities, motor co-ordination and learning and memory, respectively,
      prior to initiation of the treatment, and at Week 4, 8 and 12 postexposure. There
      were no consistent changes in the open field test, except for locomotion and
      grooming episodes. In the rotarod test, AN significantly decreased the latencies
      to fall in a dose and time-dependent manner. In the spatial water maze test, rats
      exposed to AN for 12 weeks had significantly more training times and longer
      escape latencies than control animals. These findings indicate that oral exposure
      to AN induces neurobehavioral alterations in rats.

PMID- 17439921
TI  - Risk assessment of dietary exposure to methylmercury in fish in the UK.
AB  - Risk assessment of chemicals in food is generally based upon the results of
      toxicological studies in laboratory animals, allowing for uncertainties relating
      to interspecies differences, human variability, and gaps in the database. Use of
      quantitative human data is preferable if available, as in the example of
      methylmercury. Methylmercury is a neurotoxic environmental contaminant, for which
      fish is the main source of dietary exposure. Human data from poisoning incidents
      and epidemiological studies have been used by expert committees to derive a
      guideline intake level for methylmercury, based on the susceptibility of the most
      sensitive lifestage, the developing fetus. In the UK, an expert group of
      nutritionists and toxicologists was formed to review the benefits and risks
      associated with fish consumption. A formal risk-benefit analysis was not possible
      because the nutritional data were not sufficiently quantitative. The Committee on
      Toxicity of Chemicals in Food, Consumer Products and the Environment (COT),
      therefore, modified the risk assessment approach to derive different guideline
      intake levels for different subgroups of the population. The COT opinion was used
      to provide targeted advice on how much fish can be consumed without undue risk
      from the contaminants. Consumption by adults of one weekly portion (140 g) of
      shark, swordfish or marlin, would lead to an exceedance of the guideline intake
      for methylmercury of 40-90%, set to protect the developing fetus, without
      considering intake from the rest of the diet. Pregnant women and women who may
      become pregnant within 1 year were, therefore, advised to avoid consumption of
      these species. Intakes in other adults would be within a higher guideline intake,
      set to protect groups of the population other than the developing fetus. However,
      consumption by children of one weekly portion of these species could lead to an
      exceedance of this guideline intake by up to 60%, without considering intake from
      the rest of the diet. It was, therefore, advised that consumption of these
      species by children should be avoided.

PMID- 17439922
TI  - Cyanide: critical issues in diagnosis and treatment.
AB  - The concern of a terrorist attack using cyanide, as well as the gradual awareness
      of cyanide poisoning in fire victims, has resulted in a renewed interest in the
      diagnosis and treatment of cyanide poisoning. The formerly academic presentation
      of cyanide poisoning must be replaced by more useful knowledge, which will allow
      emergency physicians and rescue workers to strongly suspect cyanide poisoning at
      the scene. Human cyanide poisonings may result from exposure to cyanide, its
      salts, or cyanogenic compounds, while residential fires are the most common
      condition of exposure. In fire victims, recognition of the cyanide toxidrome has
      been hampered by the short half-life in blood and poor stability of cyanide. In
      contrast, carboxyhemoglobin, as a marker of carbon monoxide poisoning, is easily
      measured and long-lasting. No evidence supports the assumption of the arbitrary
      fixed lethal thresholds of 50% for carboxyhemoglobin, and 3 mg/L for cyanide, in
      fire victims. Preliminary data, drawn when comparing pure carbon monoxide and
      pure cyanide poisonings, suggest that a cyanide toxidrome can be defined
      considering signs and symptoms induced by cyanide and carbon monoxide,
      respectively. Prospective studies in fire victims may provide value in clarifying
      signs and symptoms related to both toxicants. Cyanide can induce a life
      threatening poisoning from which a full recovery is possible. A number of
      experimentally efficient antidotes to cyanide exist, whose clinical use has been
      hampered due to serious side effects. The availability of potentially safer
      antidotes unveils the possibility of their value as first-line treatment, even in
      a complex clinical situation, where diagnosis is rapid and presumptive.

PMID- 17439923
TI  - Manganese does not alter the severe neurotoxicity of MPTP.
AB  - We utilized a mice model of Parkinsonism: (1) to evaluate 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity; and (2) to evaluate
      whether manganese (Mn) exposure can affect MPTP-induced neurotoxicity. A 2 x 3
      experimental design (MPTP x+/- Mn) was as follows: SS, MPTP(-) x Mn(-); SLMn,
      MPTP(-) x low Mn(+); SHMn, MPTP(-) x high Mn(+); MpS, MPTP(+) x Mn(-); MpLMn,
      MPTP(+) x low Mn(+); MpHMn, MPTP(+) x high Mn(+). We administered MPTP (30 mg/kg
      per day) to male C57BL/6 mice intraperitoneally, once a day for 5 days.
      Subsequently, mice were treated with either 2 or 8 mg/kg of MnCl(2).4H(2)O
      intraperitoneally, once a day for 3 weeks. Blood and striatal Mn levels were
      elevated in the Mnexposed groups. The number of tyrosine hydroxylase (TH)
      immunoreactive (ir) neurons in the substantia nigra pars compacta were decreased
      significantly in the MPTP-exposed groups. The densities of TH-ir axon terminals
      in caudate-putamen (CPU) were significantly decreased in the MPTP-treated groups.
      However, Mn treatment did not affect MPTP neurotoxicity. The densities of glial
      fibrillary acidic protein (GFAP)-ir astrocytes in the CPU or globus pallidus were
      significantly increased in the MPTP-treated groups. Concentrations of dopamine in
      the striatum were decreased significantly in the MPTP-exposed groups only, but Mn
      had no effect.

PMID- 17439924
TI  - Cholinesterase and monoamine oxidase activity in relation to mercury levels in
      the cerebral cortex of wild river otters.
AB  - Mercury (Hg) is a global pollutant that is neurotoxic to many mammalian species.
      The present study was conducted to determine if the bioaccumulation of Hg by wild
      river otters (Lontra canadensis) could be related to variations in the activities
      of key neurochemical enzymes. River otters were collected from Ontario and Nova
      Scotia (Canada) during the trapping seasons, spanning 2002-2004, and their brains
      were dissected into the cerebral cortex and cerebellum. The activities of
      cholinesterase (ChE) and monoamine oxidase (MAO) were measured from each sample
      and correlated with concentrations of brain Hg from the same animal. Significant
      negative correlations were found between concentrations of brain Hg and ChE
      (total Hg: r= -0.42; MeHg: r= -0.33) and MAO (total Hg: r= -0.31; MeHg: r= -0.42)
      activity in the cerebral cortex. The scatterplots relating concentrations of
      brain Hg and enzyme activity in the cerebral cortex were wedge-shaped, and could
      be fitted with quantile regression modeling, suggesting that Hg may act as a
      limiting factor for ChE and MAO activity. No relationships were found in the
      cerebellum. These data suggest that environmentally relevant concentrations of Hg
      may influence the activities of ChE and MAO in the cerebral cortex of river
      otters, and by extension, other fish-eating mammals.

PMID- 17439925
TI  - Metal transporters in intestine and brain: their involvement in metal-associated
      neurotoxicities.
AB  - The transport of essential metals and other nutrients across tight membrane
      barriers such as the gastrointestinal tract and blood-brain barrier is mediated
      by specific transport mechanisms. Specific transporters take up metals at the
      apical surface and export them at the basolateral surface, and are involved in
      their intracellular distribution. Transporters for each of the major essential
      metals, calcium, iron and zinc, have been identified. These transporters also
      mediate the transport of non-essential metals across tight membrane barriers. For
      example, the intestinal iron transporter divalent metal transporter 1 mediates
      the uptake of lead and cadmium. The levels of essential metals are strictly
      regulated by transporters. When dietary levels of essential metals are low,
      levels of the corresponding transporters increase in the intestine, after which
      there is a greater potential for increased transport of toxic metals. In the
      brain, the strict regulation of metals prevents injury that potentially would
      result from oxidative damage induced by the essential metals iron, copper and
      zinc. Indeed, the oxidative damage found in neurodegenerative diseases is likely
      to be due to higher levels of these metals. Involvement of intracellular
      transporters for copper and zinc has been shown in animal models of Alzheimer's
      disease, raising the possibility that higher levels of iron, zinc and copper
      might be due to a disruption in the activity of transporters. Accordingly,
      exposure to toxicants that affect the activity of transporters potentially could
      contribute to the aetiology/progression of neurodegenerative diseases.

PMID- 17439926
TI  - Personality, mental distress, and subjective health complaints among persons with
      environmental annoyance.
AB  - The aim of this study was to assess possible early determinants of idiopathic
      environmental intolerance (IEI), contributing to an integrated model for the
      development of IEI. Questionnaires concerning personality traits, current mental
      distress, subjective health complaints, work load and satisfaction, and options
      for recovery, were given to 84 persons from the general population attributing
      annoyance to (i) chemicals/smells (smell-annoyed (SA) n= 29); (ii) electrical
      equipment (electrically annoyed (EA) n= 16); and (iii) both smells and
      electricity (generally annoyed (GA) n= 39), but otherwise healthy and in active
      work. Compared to referents (n= 54), the EA and GA groups showed strongly
      elevated scores on 5/6 scales within the trait anxiety/neuroticism personality
      dimension, while the SA group had a slight elevation on only one anxiety scale.
      Current mental distress and subjective health complaints scores were generally
      elevated in the EA and GA groups, but only partially in the SA group. Higher
      proportions of the EA, GA, and SA groups reported low satisfaction with their
      work situation, including more frequent fatigue after work and a higher, and
      often unfulfilled, need for recovery. The findings suggest that trait anxiety is
      prominent already at prodromal stages of IEI, possibly indicating that trait
      anxiety facilitates the acquisition of attribution of health complaints to
      environmental factors.

PMID- 17439927
TI  - Neurologic symptoms in licensed pesticide applicators in the Agricultural Health
      Study.
AB  - Exposure to high levels of many pesticides has both acute and long-term
      neurologic consequences, but little is known about the neurotoxicity of chronic
      exposure to moderate pesticide levels. We analysed cross-sectional data from 18
      782 Caucasian, male, licensed pesticide applicators, enrolled in the Agricultural
      Health Study from 1993 to 1997. Applicators provided information on lifetime
      pesticide use, and 23 neurologic symptoms typically associated with pesticide
      intoxication. Increased risk of experiencing >/=10 symptoms during the year
      before enrollment was associated with cumulative pesticide use, personally mixing
      or applying pesticides, pesticide-related medical care, diagnosed pesticide
      poisoning, and events involving high personal pesticide exposure. Greatest risk
      was associated with use of organophosphate and organochlorine insecticides.
      Results were similar after stratification by pesticide use during the year before
      enrollment, or exclusion of applicators with a history of pesticide poisoning, or
      high-exposure events. Use of pesticide application methods likely to involve high
      personal exposure was associated with greater risk. Groups of symptoms reflecting
      several neurologic domains, including affect, cognition, autonomic and motor
      function, and vision, were also associated with pesticide exposure. These results
      suggest that neurologic symptoms are associated with cumulative exposure to
      moderate levels of organophosphate and organochlorine insecticides, regardless of
      recent exposure or history of poisoning.

PMID- 17439928
TI  - The neurotoxicity of alcohol.
AB  - Patterns of drinking are changing throughout the world and in many countries this
      will be detrimental to the health and welfare of the local population. Even
      uncomplicated alcoholics who have no specific neurological or hepatic problems
      show signs of regional brain damage and cognitive dysfunction. Many of these
      changes are exaggerated and other brain regions damaged in patients who have
      additional vitamin B1 (thiamine) deficiency (Wernicke-Korsakoff syndrome).
      Quantitative neuropathology techniques and improvements in neuroimaging have
      contributed significantly to the documentation of these changes but mechanisms
      underlying the damage are not understood. A human brain bank targeting alcohol
      cases has been established in Sydney, Australia and provides fresh and frozen
      tissue for alcohol researchers. The tissues can be used to test hypotheses
      developed from structural neuropathological studies or from animal models and in
      vitro studies. Identification of reversible pathological changes and preventative
      medical approaches in alcoholism should enhance rehabilitation and treatment
      efforts, thereby mitigating debilitating morbidities and reducing mortality
      associated with this universal public health problem.

PMID- 17439929
TI  - Disease activity as a major risk factor for osteonecrosis in early systemic lupus
      erythematosus.
AB  - This study Identifies the possible risk factors for osteonecrosis (ON) in a
      homogenous group of early system lupus erythematosus (SLE). Forty-six consecutive
      SLE patients (<5 years duration) followed at the Lupus Clinic, were enrolled
      between 2004 and 2005. An extensive clinical and laboratory evaluation using a
      standard electronic protocol established since 1999, including osteonecrosis
      symptoms and appropriate magnetic resonance imaging (MRI), were carried out at 1
      6 months intervals. All other asymptomatic for osteonecrosis patients at study
      entry underwent MRI. ON confirmed by MRI was found in 10 of 46 patients (22%).
      Age, disease duration, clinical vascular features, frequency of thrombophilia and
      hypofibrinolysis factors and the lipoprotein profile were comparable in patients
      with and without osteonecrosis (P > 0.05). Remarkably, the frequency of patients
      with system lupus erythematosus disease activity index (SLEDAI) > or =8 in the
      previous year of osteonecrosis clinical diagnosis was significantly higher when
      compared to patients without this manifestation (60.0% versus 19.4%, P = 0.011),
      supported by the higher glucocorticoid cumulative dose in the same period (P =
      0.045). In contrast, these two parameters evaluated in 13th-24th months preceding
      osteonecrosis diagnosis were similar in patients with and without osteonecrosis
      (P > 0.05). In the logistic regression analysis only SLEDAI remained as an
      independent risk factor for ON (OR = 6.78, CI = 1.05-43.55, P = 0.04). Disease
      activity in the previous year of ON clinical diagnosis is the main predictor
      factor for the development of this complication in early SLE.

PMID- 17439930
TI  - Genetically determined mannan-binding lectin deficiency is of minor importance in
      determining susceptibility to severe infections and vascular organ damage in
      systemic lupus erythematosus.
AB  - Deficiency of mannan-binding lectin (MBL) has been reported to impact
      susceptibility to severe infections and atherosclerosis in systemic lupus
      erythematosus (SLE). In this study, MBL gene polymorphisms were analysed in 143
      SLE patients and the frequency of severe infections and organ damage according to
      SLICC/ACR Damage Index regarding cerebrovascular accidents, angina pectoris,
      coronary by-pass surgery, myocardial infarction and peripheral arterial disease
      leading to significant tissue loss, were recorded during a mean follow-up time of
      15 years from diagnosis. In a multiple logistic regression model, smoking (P =
      0.001), hypertension (P = 0.030), alcohol intake (P = 0.027) and higher
      triglyceride concentration (P = 0.026) were associated with cerebrovascular,
      cardiovascular and peripheral arterial organ damage (CPAD), while the association
      with MBL deficiency did not reach significance (P = 0.098). Alcohol intake (>15
      g/month) was inversely correlated with CPAD (OR = 0.29, 95%CI 0.096-0.87). MBL
      deficiency was not significantly more common in SLE patients with severe
      infections in a multivariate analysis (P > 0.3). In conclusion, classical risk
      factors such as smoking, hypertension, low alcohol intake and elevated
      triglyceride concentration were relatively more important for development of CPAD
      than MBL deficiency in SLE. Furthermore, MBL deficiency did not contribute to
      development of major infections in SLE.

PMID- 17439931
TI  - Capillaroscopy is a dynamic process in mixed connective tissue disease.
AB  - To determine the clinical relevance of 'scleroderma-pattern' (SD-pattern) in
      mixed connective tissue disease (MCTD), 63 (MCTD) patients (Kasukawa's criteria)
      were consecutively selected. The main inclusion criterion was availability of
      previous nailfold capillaroscopy (NC) five years before inclusion. At entry,
      organ involvement and autoantibody evaluation were performed. The mean age and
      disease duration were 45.3 +/- 10 and 8.45 +/- 5.42 years, respectively. SD
      pattern was observed in 41 patients at entry (65%) and in 45 at previous NC
      (71.5%), P = 0.20. Ten patients (16%) changed NC, seven normalized, and three
      developed SD-pattern. Disease duration, number and frequency of organ involvement
      were similar in patients with and without SD-pattern. In contrast, analysis of
      each SD-pattern parameter revealed a significantly lower frequency of
      moderate/severe avascular areas (AA) at entry compared to previous examination
      (26.5 versus 53%, P = 0.013). Moreover, 76% of patients with interstitial lung
      disease (HRCT) had AA at entry, whereas only 24% of patients with this alteration
      did not have this NC finding (P = 0.017). Furthermore, reduced capillary density
      was more frequently observed in patients taking immunosuppressive therapy than in
      those without this medication (66.7 versus 33.3%, P = 0.001). NC in MCTD is a
      dynamic process and analysis of each SD-pattern parameter seems to be a good
      indicator of lung involvement and disease severity.

PMID- 17439932
TI  - Thickened carotid artery intima-media in rheumatoid arthritis is associated with
      elevated anticardiolipin antibodies.
AB  - Antiphospholipid and anti-oxidized LDL (anti-oxLDL) antibodies are associated
      with thrombosis and atherosclerosis. Rheumatoid arthritis (RA) is characterized
      by excess atherosclerosis and cardiovascular diseases. Our aim was to determine
      whether antiphospholipid and anti-oxLDL antibodies are associated with early
      atherosclerotic changes in RA. The levels of IgG and IgM anticardiolipin, IgG and
      IgM anti-beta-2-glycoprotein-I and anti-oxLDL autoantibodies have been evaluated
      in 82 patients having RA. Carotid artery intima-media thickness (IMT) was
      measured in the carotid arteries in the common carotid, bifurcation and internal
      carotid arteries. Elevated levels of IgG anticardiolipin antibodies were detected
      in 17 of 82 (21%) RA patients, including 7 with medium-to-high levels considered
      being clinically relevant. These patients had significantly elevated mean carotid
      and carotid bifurcation IMT compared with RA patients without elevated
      anticardiolipin. No such association was found regarding other autoantibodies
      tested. Anticardiolipin antibodies are prevalent in RA and are associated with
      early atherosclerotic changes, supporting a rational for measuring them in RA,
      and upon detection treat the patients in order to decrease chances of
      atherosclerosis progression and thrombosis.

PMID- 17439933
TI  - Premature telomere shortening in polymorphonuclear neutrophils from patients with
      systemic lupus erythematosus is related to the lupus disease activity.
AB  - We investigated whether premature telomeric loss occurred in peripheral
      polymorphonuclear neutrophils (PMN) as well as mononuclear cells (MNC) from
      patients with systemic lupus erythematosus (SLE). We measured the telomere length
      of MNC and PMN in 60 SLE patients and 26 sex-, race- and age-matched healthy
      volunteers by Southern blotting with chemiluminescence method. The possible
      predisposing factors associated with telomere change were also analysed. We found
      the telomere length of MNC and PMN shortened with age in different degrees in
      both SLE and control groups. Compared to the control group, the telomere length
      was shortened in both SLE-MNC (6.08 kb in SLE versus 6.71 kb in control, P =
      0.0008) and PMN (6.24 kb in SLE versus 6.75 kb in control, P = 0.0025). The
      average reduction in telomere length in SLE patients was equivalent to a
      premature senescence of 16.5 years in MNC and 13.4 years in PMN. In addition, the
      accelerated telomere shortening was more prominent in SLE patients younger than
      45 years old. SLE disease activity (SLEDAI) contributed remarkably to the
      accelerated telomere erosion, at least in PMN. Moreover, the telomere length of
      MNC was significantly shorter than PMN in the same SLE patients with leukopenia
      and lymphopenia. These data suggested that MNC and PMN from patients with SLE
      displayed premature and accelerated telomere shortening that SLE is an
      independent factor for it.

PMID- 17439934
TI  - Chloroquine increases low-density lipoprotein removal from plasma in systemic
      lupus patients.
AB  - Low-density lipoprotein (LDL) pathway in systemic lupus erythematosus (SLE)
      patients taking chloroquine diphosphate (CDP) was evaluated through the kinetic
      behavior of a radioactive cholesterol-rich nanoemulsion (LDE) that resembles the
      LDL lipidic structure. LDE was labeled with (14)C-cholesteryl ester ((14)C-CE),
      then IV injected in inactive female SLE patients: 10 taking CDP (CDP), 10 without
      therapy (NO THERAPY); and 10 normal subjects (CONTROL). Groups were age-matched
      and followed rigorous selection criteria of conditions that interfere in the
      lipid profile. Blood samples were collected in pre-established intervals after
      infusion for radioactivity measurement. Fasting lipoproteins were determined in
      the beginning of kinetic studies. Fractional clearance rate (FCR) of (14)C-CE was
      significantly different in the three groups (P = 0.03). In fact, a greater FCR of
      (14)C-CE was observed in CDP compared to NO THERAPY (0.076 +/- 0.037 versus 0.046
      +/- 0.021 h(-1); P < 0.05) and to CONTROL (0.0516 +/- 0.0125 h(-1); P < 0.05).
      Accordingly, a significant lower total and LDL cholesterol were observed in CDP
      (156 +/- 16 and 88 +/- 16 mg/dl) compared to NO THERAPY (174 +/- 15 and 108 +/-
      17 mg/dl; P < 0.05) and to CONTROL (200 +/- 24 and 118 +/- 23 mg/dl; P < 0.05).
      In contrast, no difference in (FCR) of (14)C-CE of NO THERAPY and CONTROL groups
      was observed. This is the first in vivo demonstration that LDE removal by LDL
      receptor from plasma is increased in SLE patients taking CDP with a consequent
      beneficial decrease in LDL-c levels.

PMID- 17439935
TI  - Bosentan use in systemic lupus erythematosus patients with pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) in patients with systemic lupus
      erythematosus (SLE) is uncommon but is associated with poor survival. This study
      aimed to examine the long-term effects of bosentan, a dual endothelin-1 receptor
      antagonist, on symptomatology, haemodynamics and quality of life measures in SLE
      patients with symptomatic PAH. Four local patients had been followed up
      prospectively with pre-defined protocol during 12-months of bosentan treatment.
      Six minute walk distance (6MWD), NYHA functional class, Borg Dyspnoea Index (BDI)
      and SF-36 were measured at 0, 3, 6, 9 and 12 months. Systolic pulmonary arterial
      pressure (PAP) was measured by transthoracic echocardiography at zero, six and 12
      months. Clinical parameters were analysed, pooling data from other SLE patients
      reported in the literature (n = 4). Bosentan was found to result in significant
      improvement in 6MWD compared to baseline [+24.8 m, +26.2 m, +54 m and +62.7 m at
      three (P = 0.001), six (P = 0.001), nine (P = 0.24) and 12 (P = 0.01) months
      respectively]. A differential effect was found with greater response in patients
      with lower exercise capacity. This was accompanied by decrease in NYHA functional
      class, BDI, transient or sustained drop in systolic PAP and mild improvement in
      SF-36 domains including mental health, vitality, social function and general
      health. Significantly deranged liver function was found in one patient.

PMID- 17439936
TI  - Development of hairy cell leukemia in a patient with antiphospholipid syndrome.
AB  - We present a young woman who was diagnosed as primary antiphospholipid syndrome
      (deep vein thrombosis and pulmonary embolism in 1999; moderate thrombocytopenia
      with high-positive anticardiolipin ELISA tests in 2002, and cerebral thrombosis
      in 2003), and then developed hairy cell leukemia (massive splenomegaly,
      neutropenia, hairy cells in blood smear and bone marrow trephine biopsy in 2004).
      A partial remission was achieved with interferon-alpha 2a therapy. After the
      initiation of 2-chloro-deoxyadenosine therapy, splenomegaly disappeared, the
      percentage of hairy cells on the bone marrow reduced below 1%, platelet count
      returned to normal levels. After complete remission was achieved for hairy cell
      leukemia proved by bone marrow trephine biopsy, antiphospholipid antibodies were
      found to be negative, and no further thromboembolic complications and
      thrombocytopenia were seen. In our literature search, we found only six cases
      that had both antiphospholipid antibodies and hairy cell leukemia. Our case is
      the first case of antiphospholipid syndrome before the development of hairy cell
      leukemia. Both hairy cell leukemia and antiphospholipid syndrome responded to
      lymphocytotoxic treatment with 2-chloro-deoxyadenosine.

PMID- 17439937
TI  - Myocardial infarction in young patients (< or =35 years of age) with systemic
      lupus erythematosus: a case report and clinical analysis of the literature.
AB  - The present study aims to report a-20-year old girl with systemic lupus
      erythematosus (SLE) who developed myocardial infarction (MI) and also aims to
      review acute myocardial infarction (AMI) in young SLE cases (< or =35 years)
      reported in the literature. We conducted a comprehensive review of the English
      literature from 1975 to 2006 to analyse data on MI in SLE patients who had
      developed AMI either at 35 or earlier. In 32 English articles, we identified 49
      SLE patients, plus our case, with AMI. They consist of 41 female and nine male
      patients, their mean age being 24 +/- 6.4 years (range of 5-35). Disease duration
      varied between 0 and 13 years. The lag time between the onset of the SLE
      manifestations and development of AMI was 7.7 +/- 5.4 year (range of 1 month to
      20.5 years). We divided the patients into three subgroups according to their
      coronary involvement type (Group I: normal coronary artery or coronary thrombosis
      (n = 16); Group II: coronary aneurysm/arteritis (n = 12); Group III: coronary
      atherosclerosis (n = 22)). The lag time between the onset of the SLE
      manifestations and development of MI in the subgroups showed variations: Group I
      < Group II < Group III. Both prevalence of renal involvement and steroid therapy
      were higher in patients with coronary atherosclerosis than were in Group I. There
      were one or more risk factors for atherosclerosis in 39 SLE patients. AMI in
      young SLE patients may be seen, albeit rare. We suggest that clinicians should
      have a low threshold for cardiac evaluation in patients with SLE. Also,
      traditional risk factors could be managed through preventive measures.

PMID- 17439938
TI  - Lack of subclinical myocardial ischaemia in Mexican patients with systemic lupus
      erythematosus without traditional risk factors for coronary artery disease.
AB  - The objective of this study was to analyse whether patients with systemic lupus
      erythematosus (SLE) without traditional risk factors for coronary artery disease
      (CAD) develop subclinical myocardial ischaemia in the first years after
      diagnosis. A cross-sectional analysis of a cohort of 200 female SLE patients was
      conducted. We selected those patients who fulfilled the American College of
      Rheumatology (ACR) SLE criteria and had no traditional risk factors for CAD,
      including diabetes mellitus, hypertension, obesity, hyperlipidemia, and smoking.
      After an initial clinical and laboratory examination, patients were evaluated
      using a baseline echocardiogram and a dobutamine and atropine stress
      echocardiogram to search for subclinical myocardial ischaemia. Forty-one patients
      were included in the study. The mean age at the time of the study was 34.5 +/-
      9.56 years (mean +/- SD). The mean age at diagnosis was 30.3 +/- 9.39 years. The
      mean time from diagnosis was 3.9 +/- 3.3 years. Baseline disease activity index
      (MEX-SLEDAI score) showed that 92.6% of patients had disease activity, although
      most patients had mild activity. A dobutamine and atropine stress echocardiogram
      was performed in 40 patients. All 40 patients had negative tests for subclinical
      myocardial ischaemia. Patients without traditional risk factors for CAD do not
      have an increased risk for subclinical myocardial ischaemia in the first years
      after diagnosis. A longitudinal follow-up study of these patients is needed to
      confirm our findings and assess if additional non-traditional risk factors for
      CAD increase the risk for myocardial ischaemia.

PMID- 17439939
TI  - Identification of an ADAM2-ADAM3 complex on the surface of mouse testicular germ
      cells and cauda epididymal sperm.
AB  - Male mice lacking ADAM2 (fertilin beta) or ADAM3 (cyritestin) are infertile;
      cauda epididymal sperm (mature sperm) from these mutant mice cannot bind to the
      egg zona pellucida. ADAM3 is barely present in Adam2-null sperm, despite normal
      levels of this protein in Adam2-null testicular germ cells (TGCs; sperm precursor
      cells). Here, we have explored the molecular basis for the loss of ADAM3 in Adam2
      null TGCs to clarify the biosynthetic and functional linkage of ADAM2 and ADAM3.
      A small portion of total ADAM3 was found present on the surface of wild-type and
      Adam2(-/-) TGCs at similar levels. In the Adam2-null TGCs, however, surface
      localized ADAM3 exhibited an increased amount of an endoglycosidase H-resistant
      form that may be related to instability of ADAM3. Moreover, we found a complex
      between ADAM2 and ADAM3 on the surface of TGCs and sperm. The intracellular
      chaperone calnexin was a component of the testicular ADAM2-ADAM3 complex. Our
      findings suggest that the association with ADAM2 is a key element for stability
      of ADAM3 in epididymal sperm. The presence of the ADAM2-ADAM3 complex in sperm
      also suggests a potential role of ADAM2 with ADAM3 in sperm binding to the egg
      zona pellucida.

PMID- 17439940
TI  - TrkA receptor "hot spots" for binding of NT-3 as a heterologous ligand.
AB  - Neurotrophins signal via Trk tyrosine kinase receptors. Nerve growth factor (NGF)
      is the cognate ligand for TrkA, the brain-derived neurotrophic factor for TrkB,
      and NT-3 for TrkC. NT-3 also binds TrkA as a lower affinity heterologous ligand.
      Because neurotrophin-3 (NT-3) interactions with TrkA are biologically relevant,
      we aimed to define the TrkA "hot spot" functional docking sites of NT-3. The Trk
      extracellular domain consists of two cysteine-rich subdomains (D1 and D3),
      flanking a leucine-rich subdomain (D2), and two immunoglobulin-like subdomains
      IgC1(D4) and IgC2(D5). Previously, the D5 subdomain was defined as the primary
      ligand-binding site of neurotrophins for their cognate receptors (e.g. NGF binds
      and activates through TRKA-D5 hot spots). Here binding studies with truncated and
      chimeric extracellular subdomains show that TRKA-D5 also includes an NT-3 docking
      and activation hot spot (site 1), and competition studies show that the NGF and
      NT-3 hot spots on TRKA-D5 are distinct but partially overlapping. In addition,
      ligand binding studies provide evidence for an NT-3-binding/allosteric site on
      TRKA-D4 (site 2). NT-3 docking on sites 1 and/or 2 partially blocks NGF binding.
      Functional survival studies showed that sites 1 and 2 regulate TrkA activation.
      NT-3 docking on both sites 1 and 2 affords full agonism, which can be additive
      with NGF activation of Trk. However, NT-3 docking solely on site 1 is partially
      agonistic but noncompetitively antagonizes NGF binding and activation of Trk.
      This study demonstrates that Trk signaling is more complex than previously
      thought because it involves several receptor subdomains and hot spots.

PMID- 17439941
TI  - Substrate-mediated regulation of cullin neddylation.
AB  - Cullin-based E3 ligases are a large family of multi-subunit ubiquitin ligases
      with diverse cellular functions, including the regulation of the cell cycle, of
      the DNA damage response, and of various transcription factors. These ligases are
      composed of one of six mammalian cullin homologs (Cul1, Cul2, Cul3, Cul4a, Cul4b,
      and Cul5), the Ring finger containing protein Roc1/Rbx1, and cullin homolog
      specific adaptor and substrate recognition subunits. To be active, cullin-based
      ligases require the covalent modification of a conserved lysine residue in the
      cullin protein with the ubiquitin-like protein Nedd8. We show in this study that
      in intact cells Cul1 neddylation is dependent on binding to adaptor proteins and
      substrate recognition subunits. Mutant Cul1 that is unable to recruit adaptor and
      substrate recognition subunits exhibits markedly reduced neddylation, and
      inhibiting binding of adaptor and substrate recognition subunits to wild type
      Cul1 reduces Nedd8 modification. This regulatory mechanism also extends to other
      cullin-based E3 ligases, including Cul2, Cul3, and Cul4a. The regulation of
      cullin neddylation by adaptor proteins and substrate recognition subunits in
      cells was found to be independent of both CAND1 and the COP9 signalosome, two
      negative regulators of cullin Nedd8 modification. Using hypoxia-inducible factor
      1alpha (HIF-1alpha), a substrate of the Elongin B/C-Cul2-VHL ligase, we
      demonstrate the critical role of substrate binding to promote Cul2 neddylation in
      a manner that does not require substrate ubiquitination but may involve a
      conformational change. These findings suggest a mechanism through which
      availability of substrate recognition subunits and substrates can regulate the
      ubiquitin ligase activity.

PMID- 17439942
TI  - Butein, a tetrahydroxychalcone, inhibits nuclear factor (NF)-kappaB and NF-kappaB
      regulated gene expression through direct inhibition of IkappaBalpha kinase beta
      on cysteine 179 residue.
AB  - Although butein (3,4,2',4'-tetrahydroxychalcone) is known to exhibit anti
      inflammatory, anti-cancer, and anti-fibrogenic activities, very little is known
      about its mechanism of action. Because numerous effects modulated by butein can
      be linked to interference with the NF-kappaB pathway, we investigated in detail
      the effect of this chalcone on NF-kappaB activity. As examined by DNA binding, we
      found that butein suppressed tumor necrosis factor (TNF)-induced NF-kappaB
      activation in a dose- and time-dependent manner; suppressed the NF-kappaB
      activation induced by various inflammatory agents and carcinogens; and inhibited
      the NF-kappaB reporter activity induced by TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1,
      and IKK-beta. We also found that butein blocked the phosphorylation and
      degradation of IkappaBalpha by inhibiting IkappaBalpha kinase (IKK) activation.
      We found the inactivation of IKK by butein was direct and involved cysteine
      residue 179. This correlated with the suppression of phosphorylation and the
      nuclear translocation of p65. In this study, butein also inhibited the expression
      of the NF-kappaB-regulated gene products involved in anti-apoptosis (IAP2, Bcl-2,
      and Bcl-xL), proliferation (cyclin D1 and c-Myc), and invasion (COX-2 and MMP-9).
      Suppression of these gene products correlated with enhancement of the apoptosis
      induced by TNF and chemotherapeutic agents; and inhibition of cytokine-induced
      cellular invasion. Overall, our results indicated that antitumor and anti
      inflammatory activities previously assigned to butein may be mediated in part
      through the direct inhibition of IKK, leading to the suppression of the NF-kappaB
      activation pathway.

PMID- 17439943
TI  - Singar1, a novel RUN domain-containing protein, suppresses formation of surplus
      axons for neuronal polarity.
AB  - Although neuronal functions depend on their robust polarity, the mechanisms that
      ensure generation and maintenance of only a single axon remain poorly understood.
      Using highly sensitive two-dimensional electrophoresis-based proteomics, we
      identified here a novel protein, single axon-related
      (singar)1/KIAA0871/RPIPx/RUFY3, which contains a RUN domain and is predominantly
      expressed in the brain. Singar1 expression became up-regulated during
      polarization of cultured hippocampal neurons and remained at high levels
      thereafter. Singar1 was diffusely localized in hippocampal neurons and moderately
      accumulated in growth cones of minor processes and axons. Overexpression of
      singar1 did not affect normal neuronal polarization but suppressed the formation
      of surplus axons induced by excess levels of shootin1, a recently identified
      protein located upstream of phosphoinositide-3-kinase and involved in neuronal
      polarization. Conversely, reduction of the expression of singar1 and its splicing
      variant singar2 by RNA interference led to an increase in the population of
      neurons bearing surplus axons, in a phosphoinositide-3-kinase-dependent manner.
      Overexpression of singar2 did not suppress the formation of surplus axons induced
      by shootin1. We propose that singar1 ensures the robustness of neuronal polarity
      by suppressing formation of surplus axons.

PMID- 17439944
TI  - The retinoblastoma protein is an essential mediator of osteogenesis that links
      the p204 protein to the Cbfa1 transcription factor thereby increasing its
      activity.
AB  - Bone formation requires the coordinated activity of numerous proteins including
      the transcription factor core-binding factor alpha1 (Cbfa1). Deregulation of
      Cbfa1 results in metabolic bone diseases including osteoporosis and
      osteopetrosis. The retinoblastoma protein (pRb) that is required for osteogenesis
      binds Cbfa1. We reported earlier that the p200 family protein p204, which is
      known to be involved in the differentiation of skeletal muscle myotubes, cardiac
      myocytes, and macrophages, also serves as a cofactor of Cbfa1 and promotes
      osteogenesis. In this study we established that suppression of p204 expression by
      an adenovirus construct encoding p204 antisense RNA inhibited osteoblast-specific
      gene activation by Cbfa1 in an osteogenesis assay involving the pluripotent C2C12
      mesenchymal cell line. Using protein-protein interaction assays we established
      that Cbfa1, pRb, and p204 form a ternary complex in which pRb serves as a linker
      connecting p204 and Cbfa1. Chromatin immunoprecipitation assays revealed the
      binding of such a p204-pRb-Cbfa1 transcription factor complex to the promoter of
      the osteocalcin gene. The pRb requirement of the stimulation of Cbfa1 activity by
      p204 was established in experiments involving p204 mutants lacking one or two pRb
      binding (LXCXE) motifs. Such mutants failed to enhance the Cbfa1-dependent
      transactivation of gene expression as well as osteogenesis. Furthermore, as
      revealed in reporter gene and in vitro osteogenesis assays p204 synergized with
      pRb in the stimulation of Cbfa1-dependent gene activation and osteoblast
      differentiation.

PMID- 17439945
TI  - AKT-dependent HspB1 (Hsp27) activity in epidermal differentiation.
AB  - AKT activity has been reported in the epidermis associated with keratinocyte
      survival and differentiation. We show in developing skin that Akt activity
      associates first with post-proliferative, para-basal keratinocytes and later with
      terminally differentiated keratinocytes that are forming the fetal stratum
      corneum. In adult epidermis the dominant Akt activity is in these highly
      differentiated granular keratinocytes, involved in stratum corneum assembly.
      Stratum corneum is crucial for protective barrier activity, and its formation
      involves complex and poorly understood processes such as nuclear dissolution,
      keratin filament aggregation, and assembly of a multiprotein cell cornified
      envelope. A key protein in these processes is filaggrin. We show that one target
      of Akt in granular keratinocytes is HspB1 (heat shock protein 27). Loss of
      epidermal HspB1 caused hyperkeratinization and misprocessing of filaggrin. Akt
      mediated HspB1 phosphorylation promotes a transient interaction with filaggrin
      and intracellular redistribution of HspB1. This is the first demonstration of a
      specific interaction between HspB1 and a stratum corneum protein and indicates
      that HspB1 has chaperone activity during stratum corneum formation. This work
      demonstrates a new role for Akt in epidermis.

PMID- 17439946
TI  - A novel regulatory role for stromal-derived factor-1 signaling in bone
      morphogenic protein-2 osteogenic differentiation of mesenchymal C2C12 cells.
AB  - Stromal-derived factor 1 (SDF-1) is a chemokine with important functions in
      development and postnatal tissue homeostasis. SDF-1 signaling via the G-protein
      coupled receptor CXCR4 regulates the recruitment of stem and precursor cells to
      support tissue-specific repair or regeneration. In this study we examined the
      contribution of SDF-1 signaling to osteogenic differentiation of mesenchymal
      C2C12 cells induced by bone morphogenic protein 2 (BMP2). Blocking SDF-1
      signaling before BMP2 stimulation by treatment with siRNA, antibodies against SDF
      1 or CXCR4, or the G-protein-coupled receptor inhibitor pertussis toxin strongly
      suppressed BMP2 induction of osteogenic differentiation in C2C12 cells, as
      evidenced by an early decrease in the expression of the myogenesis inhibitor Id1,
      the osteogenic master regulators Runx2 and Osx, the osteoblast-associated
      transcription factors JunB, Plzf, Msx2, and Dlx5, and later of the bone marker
      proteins osteocalcin and alkaline phosphatase. Similarly, blocking SDF-1/CXCR4
      signaling strongly inhibited BMP2-induced osteogenic differentiation of ST2 bone
      marrow stromal cells. Moreover, we found that the interaction between SDF-1 and
      BMP2 signaling was mediated via intracellular Smads and MAPK activation. Our data
      provide the first evidence for a co-requirement of the SDF-1/CXCR4 signaling axis
      in BMP2-induced osteogenic differentiation of C2C12 and ST2 cells and, thus,
      uncover a new potential target for modulation of osteogenesis.

PMID- 17439947
TI  - Ribosomal protein rpS2 is hypomethylated in PRMT3-deficient mice.
AB  - PRMT3 is a type I arginine methyltransferase that resides in the cytoplasm. A
      large proportion of this cystosolic PRMT3 is found associated with ribosomes. It
      is tethered to the ribosomes through its interaction with rpS2, which is also its
      substrate. Here we show that mouse embryos with a targeted disruption of PRMT3
      are small in size but survive after birth and attain a normal size in adulthood,
      thus displaying Minute-like characteristics. The ribosome protein rpS2 is
      hypomethylated in the absence of PRMT3, demonstrating that it is a bona fide, in
      vivo PRMT3 substrate that cannot be modified by other PRMTs. Finally, the levels
      40 S, 60 S, and 80 S monosomes and polyribosomes are unaffected by the loss of
      PRMT3, but there are additional as yet unidentified proteins that co-fractionate
      with ribosomes that are also dedicated PRMT3 substrates.

PMID- 17439948
TI  - Identification of a HoxA10 activation domain necessary for transcription of the
      gene encoding beta3 integrin during myeloid differentiation.
AB  - Transcription of the ITGB3 gene, which encodes beta3 integrin, increases during
      myeloid differentiation. alphavbeta3 integrin mediates adhesion to fibronectin or
      vitronectin and regulates various aspects of the inflammatory response in mature
      phagocytes. In these studies, we found that the homeodomain transcription factor
      HoxA10 interacted with a specific ITGB3 cis element and activated transcription
      of this gene during myeloid differentiation. We also found that increased
      fibronectin adhesion in differentiating myeloid cells was dependent upon this
      HoxA10-induced increase in beta3 integrin expression. We determined that
      activation of ITGB3 transcription required a HoxA10 domain that was not identical
      to the "hexapeptide" that mediates interaction of Hox and Pbx proteins. This
      activation domain was also not identical to a previously identified HoxA10
      repression domain that mediates interaction with transcriptional co-repressors.
      Instead, this HoxA10 activation domain had homology to "PQ" protein-protein
      interaction domains that have been described previously in other transcription
      factors. Consistent with this, we found that the HoxA10 PQ-like domain recruited
      the CREB-binding protein (CBP) to the ITGB3 promoter. This was associated with an
      increase in local histone acetylation in vivo. In immature myeloid cells, we
      previously determined that HoxA10 repressed transcription of the CYBB and NCF2
      genes, which encode the phagocyte oxidase proteins gp91(PHOX) and p67(PHOX),
      respectively. Therefore, our studies indicated that HoxA10 either activates or
      represses gene transcription at various points during myelopoiesis. Our studies
      also suggested that HoxA10 is a bifunctional protein that is involved in dynamic
      regulation of multiple aspects of phagocyte phenotype and function.

PMID- 17439949
TI  - Stress-responsive Gln3 localization in Saccharomyces cerevisiae is separable from
      and can overwhelm nitrogen source regulation.
AB  - Intracellular localization of Saccharomyces cerevisiae GATA family transcription
      activator, Gln3, is used as a downstream readout of rapamycin-inhibited Tor1,2
      control of Tap42 and Sit4 activities. Gln3 is cytoplasmic in cells provided with
      repressive nitrogen sources such as glutamine and is nuclear in cells growing
      with a derepressive nitrogen source such as proline or those treated with
      rapamycin or methionine sulfoximine (Msx). Although gross Gln3-Myc13
      phosphorylation levels in wild type cells do not correlate with nitrogen source
      determined intracellular Gln3-Myc13 localization, the phosphorylation levels are
      markedly influenced by several environmental perturbations. Msx treatment
      increases Snf1-independent Gln3-Myc13 phosphorylation, whereas carbon starvation
      increases both Snf1-dependent and -independent Gln3-Myc13 phosphorylation. Here
      we demonstrate that a broad spectrum of environmental stresses (temperature,
      osmotic, and oxidative) increase Gln3-Myc13 phosphorylation. In parallel, these
      stresses elicit rapid (<5 min for NaCl) Gln3-Myc13 relocalization from the
      nucleus to the cytoplasm. The response of Gln3-Myc13 localization to stressful
      conditions can completely overwhelm its response to nitrogen source quality or
      inhibitor-generated disruption of the Tor1,2 signal transduction pathway. Adding
      NaCl to cells cultured under conditions in which Gln3-Myc13 is normally nuclear,
      i.e. proline-grown, nitrogen-starved, Msx-, caffeine-, and rapamycin-treated wild
      type cells, or ure2Delta cells, results in its prompt relocalization to the
      cytoplasm. Together these data identify a major new level of regulation to which
      Gln3 responds, and adds a new dimension to mechanistic studies of the regulation
      of this transcription factor.

PMID- 17439950
TI  - Small molecule inhibitors of a glycoside hydrolase attenuate inducible AmpC
      mediated beta-lactam resistance.
AB  - The increasing spread of plasmid-borne ampC-ampR operons is of considerable
      medical importance, since the AmpC beta-lactamases they encode confer high level
      resistance to many third generation cephalosporins. Induction of AmpC beta
      lactamase from endogenous or plasmid-borne ampC-ampR operons is mediated by a
      catabolic inducer molecule, 1,6-anhydro-N-acetylmuramic acid (MurNAc) tripeptide,
      an intermediate of the cell wall recycling pathway derived from the
      peptidoglycan. Here we describe a strategy for attenuating the antibiotic
      resistance associated with the ampC-ampR operon by blocking the formation of the
      inducer molecule using small molecule inhibitors of NagZ, the glycoside hydrolase
      catalyzing the formation of this inducer molecule. The structure of the NagZ
      inhibitor complex provides insight into the molecular basis for inhibition and
      enables the development of inhibitors with 100-fold selectivity for NagZ over
      functionally related human enzymes. These PUGNAc-derived inhibitors reduce the
      minimal inhibitory concentration (MIC) values for several clinically relevant
      cephalosporins in both wild-type and AmpC-hyperproducing strains lacking
      functional AmpD.

PMID- 17439951
TI  - Key role of amino acid residues in the dimerization and catalytic activation of
      the autolysin LytA, an important virulence factor in Streptococcus pneumoniae.
AB  - LytA, the main autolysin of Streptococcus pneumoniae, was the first member of the
      bacterial N-acetylmuramoyl-l-alanine amidase (NAM-amidase) family of proteins to
      be well characterized. This autolysin degrades the peptidoglycan bonds of
      pneumococcal cell walls after anchoring to the choline residues of the cell wall
      teichoic acids via its choline-binding module (ChBM). The latter is composed of
      seven repeats (ChBRs) of approximately 20 amino acid residues. The translation
      product of the lytA gene is the low-activity E-form of LytA (a monomer), which
      can be "converted" (activated) in vitro by choline into the fully active C-form
      at low temperature. The C-form is a homodimer with a boomerang-like shape. To
      study the structural requirements for the monomer-to-dimer modification and to
      clarify whether "conversion" is synonymous with dimerization, the biochemical
      consequences of replacing four key amino acid residues of ChBR6 and ChBR7 (the
      repeats involved in dimer formation) were determined. The results obtained with a
      collection of 21 mutated NAM-amidases indicate that Ile-315 is a key amino acid
      residue in both LytA activity and folding. Amino acids with a marginal position
      in the solenoid structure of the ChBM were of minor influence in dimer stability;
      neither the size, polarity, nor aromatic nature of the replacement amino acids
      affected LytA activity. In contrast, truncated proteins were drastically impaired
      in their activity and conversion capacity. The results indicate that dimerization
      and conversion are different processes, but they do not answer the questions of
      whether conversion can only be achieved after a dimer formation step.

PMID- 17439952
TI  - The anti-inflammatory effects of selenium are mediated through 15-deoxy
      Delta12,14-prostaglandin J2 in macrophages.
AB  - Selenium is an essential micronutrient that suppresses the redox-sensitive
      transcription factor NF-kappaB-dependent pro-inflammatory gene expression. To
      understand the molecular mechanisms underlying the anti-inflammatory property of
      selenium, we examined the activity of a key kinase of the NF-kappaB cascade,
      IkappaB-kinase beta (IKKbeta) subunit, as a function of cellular selenium status
      in murine primary bone marrow-derived macrophages and RAW264.7 macrophage-like
      cell line. In vitro kinase assays revealed that selenium supplementation
      decreased the activity of IKKbeta in lipopolysaccharide (LPS)-treated
      macrophages. Stimulation by LPS of selenium-supplemented macrophages resulted in
      a time-dependent increase in 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2)
      formation, an endogenous inhibitor of IKKbeta activity. Further analysis revealed
      that inhibition of IKKbeta activity in selenium-supplemented cells correlated
      with the Michael addition product of 15d-PGJ2 with Cys-179 of IKKbeta, while the
      formation of such an adduct was significantly decreased in the selenium-deficient
      macrophages. In addition, anti-inflammatory activities of selenium were also
      mediated by the 15d-PGJ2-dependent activation of the peroxisome proliferator
      activated nuclear receptor-gamma in macrophages. Experiments using specific
      cyclooxygenase (COX) inhibitors and genetic knockdown approaches indicated that
      COX-1, and not the COX-2 pathway, was responsible for the increased synthesis of
      15d-PGJ2 in selenium-supplemented macrophages. Taken together, our results
      suggest that selenium supplementation increases the production of 15d-PGJ2 as an
      adaptive response to protect cells against oxidative stress-induced pro
      inflammatory gene expression. More specifically, modification of protein thiols
      by 15d-PGJ2 represents a previously undescribed code for redox regulation of gene
      expression by selenium.

PMID- 17439953
TI  - A novel pathway to enhance adipocyte differentiation of 3T3-L1 cells by up
      regulation of lipocalin-type prostaglandin D synthase mediated by liver X
      receptor-activated sterol regulatory element-binding protein-1c.
AB  - Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is expressed in adipocytes
      and is proposed to be involved in the regulation of glucose tolerance and
      atherosclerosis in type 2 diabetes, because L-PGDS gene knock-out mice show
      abnormalities in these functions. However, the role of L-PGDS and the regulation
      mechanism governing its gene expression in adipocytes remain unclear. Here, we
      applied small interference RNA of L-PGDS to mouse 3T3-L1 cells and found that it
      suppressed differentiation of these cells into adipocytes. Reporter analysis of
      the mouse L-PGDS promoter demonstrated that a responsive element for liver
      receptor homolog-1 (LRH-1) at -233 plays a critical role in preadipocytic 3T3-L1
      cells. Moreover, we identified two sterol regulatory elements (SREs) at -194 to
      be cis-elements for activation of L-PGDS gene expression in adipocytic 3T3-L1
      cells. L-PGDS mRNA was induced in response to synthetic liver X receptor agonist,
      T0901317, through activation of the expression of SRE-binding protein-1c (SREBP
      1c) in the adipocytic 3T3-L1 cells. The results of electrophoretic mobility shift
      assay and chromatin immunoprecipitation assay revealed that LRH-1 and SREBP-1c
      bound to their respective binding elements in the promoter of L-PGDS gene. Small
      interference RNA-mediated suppression of LRH-1 or SREBP-1c decreased L-PGDS gene
      expression in preadipocytic or adipocytic 3T3-L1 cells, respectively. These
      results indicate that L-PGDS gene expression is activated by LRH-1 in
      preadipocytes and by SREBP-1c in adipocytes. Liver X receptor-mediated up
      regulation of L-PGDS through activation of SREBP-1c is a novel path-way to
      enhance adipocyte differentiation.

PMID- 17439954
TI  - ArsD residues Cys12, Cys13, and Cys18 form an As(III)-binding site required for
      arsenic metallochaperone activity.
AB  - The ArsA ATPase is the catalytic subunit of the ArsAB pump encoded by the
      arsRDABC operon of Escherichia coli plasmid R773. ArsD is a metallochaperone that
      delivers As(III) to ArsA, increasing its affinity for As(III), thus conferring
      resistance to environmental concentrations of arsenic. R773 ArsD is a homodimer
      with three vicinal cysteine pairs, Cys(12)-Cys(13), Cys(112)-Cys(113), and
      Cys(119)-Cys(120), in each subunit. Each vicinal pair binds As(III) or Sb(III).
      Alignment of the primary sequence of homologues of ArsD indicates that only the
      first vicinal cysteine pair, Cys(12)-Cys(13), and an additional cysteine,
      Cys(18), are conserved. The effect of cysteine-to-alanine substitutions and
      truncations were examined. By yeast two-hybrid analysis, nearly all of the ArsD
      mutants were able to interact with wild type ArsD, indicating that the mutations
      do not interfere with dimerization. ArsD mutants with alanines substituting for
      Cys(112), Cys(113), Cys(119), or Cys(120) individually or in pairs or truncations
      lacking the vicinal pairs retained ability to interact with ArsA and to activate
      its ATPase activity. Cells expressing these mutants retained ArsD-enhanced
      As(III) efflux and resistance. In contrast, mutants with substitutions of
      conserved Cys(12), Cys(13), or Cys(18), individually or in pairs, were unable to
      activate ArsA or to enhance the activity of the ArsAB pump. We propose that ArsD
      residues Cys(12), Cys(13), and Cys(18), but not Cys(112), Cys(113), Cys(119), or
      Cys(120), are required for delivery of As(III) to and activation of the ArsAB
      pump.

PMID- 17439955
TI  - Mutation and haplotype analysis for Duchenne muscular dystrophy by single cell
      multiple displacement amplification.
AB  - Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder with
      mutational heterogeneity. The scarcity of DNA from single cells in
      preimplantation genetic diagnosis (PGD) for DMD limits comprehensive genetic
      testing. Multiple displacement amplification (MDA) is reported to generate large
      amounts of template and give the most complete coverage and unbiased
      amplification to date. Here, we developed mutation and haplotype analysis in
      conjunction with gender determination on MDA products of single cells providing a
      generic approach that widens availability of PGD for female carriers with varied
      mutations. MDA amplified with 98.5% success for single lymphocytes and 94.2%
      success for single blastomeres, which was evaluated on 60 lymphocytes and 40
      blastomeres. A total of six commonly mutant exons, eight short tandem repeat
      markers within dystrophin gene and amelogenin were incorporated into subsequent
      singleplex PCR assays. The mean allele dropout rate was 9.0% for single
      lymphocytes and 25.5% for single blastomeres. None of the blank controls gave a
      positive signal. Genotyping of each pedigree for three families provided 2-3
      fully informative alleles per dystrophin haplotype besides specific mutant exons
      and amelogenin. We suggest that this approach is reliable to identify non-carrier
      female embryos other than unaffected male embryos and reduce the risk of
      misdiagnosis.

PMID- 17439956
TI  - Methylenetetrahydrofolate reductase gene polymorphisms and the risk of
      anencephaly in Mexico.
AB  - The precise etiology of neural tube defects (NTDs) is not known. There is some
      evidence that mutations in MTHFR gene provide susceptibility to NTDs in some
      populations; however, other studies have not found this association. One of the
      problems with previous studies is that they treat NTDs as a homogeneous group,
      when specific defects could have different etiologies. We conducted a case
      control study specifically for anencephaly, based on the Mexican Epidemiological
      Surveillance System of Neural Tube Defects to evaluate its association with
      maternal MTHFR 677C > T and 1298A > C polymorphisms, in three states with high
      frequencies of NTDs: Puebla, Estado de Mexico and Guerrero. We interviewed and
      collected blood samples from 118 case mothers and 112 control mothers. The
      questionnaire included information on their reproductive history, socioeconomic
      characteristics, prenatal care, tobacco and alcohol use, presence of chronic
      diseases, acute illnesses and fever, consumption of multivitamins and drugs
      during the periconceptional period. After adjusting for potential confounders,
      the risk from the mutated homozygous mothers (677TT genotype) was significantly
      higher than that from mothers with 677CC genotype (OR 3.16, 95% CI 1.29-7.73); in
      the case of the heterozygous mothers, an increased risk of anencephaly was
      observed, even though this was not statistically significant (OR 1.81 95% CI 0.78
      4.25). The association found between maternal 677TT genotype and anencephaly and
      the elevated presence of the 677T allele among Mexican women of fertile age urges
      intensifying folic acid supplementation which has proved to modify this genetic
      risk in other populations.

PMID- 17439957
TI  - Complex translational regulation of BACE1 involves upstream AUGs and stimulatory
      elements within the 5' untranslated region.
AB  - BACE1 is the protease responsible for the production of amyloid-beta peptides
      that accumulate in the brain of Alzheimer's disease (AD) patients. BACE1
      expression is regulated at the transcriptional, as well as post-transcriptional
      level. Very high BACE1 mRNA levels have been observed in pancreas, but the
      protein and activity were found mainly in brain. An up-regulation of the protein
      has been described in some AD patients without a change in transcript levels. The
      features of BACE1 5' untranslated region (5' UTR), such as the length, GC
      content, evolutionary conservation and presence of upstream AUGs (uAUGs),
      indicate an important regulatory role of this 5' UTR in translational control. We
      demonstrate that, in brain and pancreas, almost all of the native BACE1 mRNA
      contains the full-length 5' UTR. RNA transfection and in vitro translation show
      that translation is mainly inhibited by the presence of the uAUGs. We provide a
      mutational analysis that highlight the second uAUG as the main inhibitory element
      while mutations of all four uAUGs fully de-repress translation. Furthermore, we
      have evidence that a sequence within the region 222-323 of the BACE1 5' UTR has a
      stimulatory effect on translation that might depend on the presence of trans
      acting factors.

PMID- 17439958
TI  - Thermodynamics and kinetics for base-pair opening in the P1 duplex of the
      Tetrahymena group I ribozyme.
AB  - The thermodynamics and kinetics for base-pair opening of the P1 duplex of the
      Tetrahymena group I ribozyme were studied by NMR hydrogen exchange experiments.
      The apparent equilibrium constants for base pair opening were measured for most
      of the imino protons in the P1 duplex using the base catalysts NH3, HPO4(2-) or
      TRIS. These equilibrium constants were also measured for several modified P1
      duplexes, and the C-2.G23 base pair was the most stable base pair in all the
      duplexes. The conserved U-1*G22 base pair is required for activity of the
      ribozyme and the data here show that this wobble base pair destabilizes
      neighboring base pairs on only one side of the wobble. A 2'-OMe modification on
      the U-3 residue stabilized its own base pair but had little effect on the
      neighboring base pairs. Three base pairs, U-1*G22, C-2*G23 and A2*U21 showed
      unusual equilibrium constants for opening and possible implications of the
      opening thermodynamics of these base pairs on the undocking rates of the P1 helix
      with catalytic core are discussed.

PMID- 17439959
TI  - All APOBEC3 family proteins differentially inhibit LINE-1 retrotransposition.
AB  - Approximately 17% of the human genome is comprised of long interspersed nuclear
      element 1 (LINE-1, L1) non-LTR retrotransposons. L1 retrotransposition is known
      to be the cause of several genetic diseases, such as hemophilia A, Duchene
      muscular dystrophy, and so on. The L1 retroelements are also able to cause colon
      cancer, suggesting that L1 transposition could occur not only in germ cells, but
      also in somatic cells if innate immunity would not function appropriately. The
      mechanisms of L1 transposition restriction in the normal cells, however, are not
      fully defined. We here show that antiretroviral innate proteins, human APOBEC3
      (hA3) family members, from hA3A to hA3H, differentially reduce the level of L1
      retrotransposition that does not correlate either with antiviral activity against
      Vif-deficient HIV-1 and murine leukemia virus, or with patterns of subcellular
      localization. Importantly, hA3G protein inhibits L1 retrotransposition, in
      striking contrast to the recent reports. Inhibitory effect of hA3 family members
      on L1 transposition might not be due to deaminase activity, but due to novel
      mechanism(s). Thus, we conclude that all hA3 proteins act to differentially
      suppress uncontrolled transposition of L1 elements.

PMID- 17439960
TI  - DNA modification by sulfur: analysis of the sequence recognition specificity
      surrounding the modification sites.
AB  - The Dnd (DNA degradation) phenotype, reflecting a novel DNA modification by
      sulfur in Streptomyces lividans 1326, was strongly aggravated when one (dndB) of
      the five genes (dndABCDE) controlling it was mutated. Electrophoretic banding
      patterns of a plasmid (pHZ209), reflecting DNA degradation, displayed a clear
      change from a preferential modification site in strain 1326 to more random
      modifications in the mutant. Fourteen randomly modifiable sites on pHZ209 were
      localized, and each seemed to be able to be modified only once. Residues in a
      region (5'-c-cGGCCgccg-3') including a highly conserved 4-bp central core (5'
      GGCC-3') in a well-documented preferential modification site were assessed for
      their necessity by site-directed mutagenesis. While the central core (GGCC) was
      found to be stringently required in 1326 and in the mutant, 'gccg' flanking its
      right could either abolish or reduce the modification frequency only in the
      mutant, and two separate nucleotides to the left had no dramatic effect. The lack
      of essentiality of DndB for S-modification suggests that it might only be
      required for enhancing or stabilizing the activity of a protein complex at the
      required preferential modification site, or resolving secondary structures
      flanking the modifiable site(s), known to constitute an obstacle for efficient
      modification.

PMID- 17439961
TI  - Mapping translocation breakpoints using a wheat microarray.
AB  - We report mapping of translocation breakpoints using a microarray. We used
      complex RNA to compare normal hexaploid wheat (17,000 Mb genome) to a ditelosomic
      stock missing the short arm of chromosome 1B (1BS) and wheat-rye translocations
      that replace portions of 1BS with rye 1RS. Transcripts detected by a probe set
      can come from all three Triticeae genomes in ABD hexaploid wheat, and sequences
      of homoeologous genes on 1AS, 1BS and 1DS often differ from each other. Absence
      or replacement of 1BS therefore must sometimes result in patterns within a probe
      set that deviate from hexaploid wheat. We termed these 'high variance probe sets'
      (HVPs) and examined the extent to which HVPs associated with 1BS aneuploidy are
      related to rice genes on syntenic rice chromosome 5 short arm (5S). We observed
      an enrichment of such probe sets to 15-20% of all HVPs, while 1BS represents
      approximately 2% of the total genome. In total 257 HVPs constitute wheat 1BS
      markers. Two wheat-rye translocations subdivided 1BS HVPs into three groups,
      allocating translocation breakpoints to narrow intervals defined by rice 5S
      coordinates. This approach could be extended to the entire wheat genome or any
      organism with suitable aneuploid or translocation stocks.

PMID- 17439962
TI  - Loop II of DNA polymerase beta is important for polymerization activity and
      fidelity.
AB  - The accurate replication and transmission of genetic information is critical in
      the life of an organism. During its entire lifespan, the genetic information is
      constantly under attack from endogenous and exogenous sources of damage. To
      ensure that the content of its genetic information is faithfully preserved for
      synthesis and transmission, eukaryotic cells have developed a complex system of
      genomic quality control. Key players in this process are DNA polymerases, the
      enzymes responsible for synthesizing the DNA, because errors introduced into the
      genome by polymerase can result in mutations. We use DNA polymerase beta (pol
      beta) as a model system to investigate mechanisms of preserving fidelity during
      nucleotide incorporation. In the study described here, we characterized the role
      that loop II of pol beta plays in maintaining the activity and fidelity of pol
      beta. We report here that the absence or shortening of loop II compromises the
      catalytic activity of pol beta. Our data also show that loop variants of a
      specific length have a lower fidelity when compared to the wild-type polymerase.
      Taken together, our results indicate that loop II is important for the catalytic
      activity and fidelity of pol beta.

PMID- 17439963
TI  - Recruitment of DNA repair synthesis machinery to sites of DNA damage/repair in
      living human cells.
AB  - The eukaryotic sliding DNA clamp, proliferating cell nuclear antigen (PCNA), is
      essential for DNA replication and repair synthesis. In order to load the ring
      shaped, homotrimeric PCNA onto the DNA double helix, the ATPase activity of the
      replication factor C (RFC) clamp loader complex is required. Although the
      recruitment of PCNA by RFC to DNA replication sites has well been documented, our
      understanding of its recruitment during DNA repair synthesis is limited. In this
      study, we analyzed the accumulation of endogenous and fluorescent-tagged proteins
      for DNA repair synthesis at the sites of DNA damage produced locally by UVA-laser
      micro-irradiation in HeLa cells. Accumulation kinetics and in vitro pull-down
      assays of the large subunit of RFC (RFC140) revealed that there are two distinct
      modes of recruitment of RFC to DNA damage, a simultaneous accumulation of RFC140
      and PCNA caused by interaction between PCNA and the extreme N-terminus of RFC140
      and a much faster accumulation of RFC140 than PCNA at the damaged site.
      Furthermore, RFC140 knock-down experiments showed that PCNA can accumulate at DNA
      damage independently of RFC. These results suggest that immediate accumulation of
      RFC and PCNA at DNA damage is only partly interdependent.

PMID- 17439964
TI  - Recovery of bisulfite-converted genomic sequences in the methylation-sensitive
      QPCR.
AB  - Many methods for the detection of genomic DNA methylation states have appeared.
      Currently, nearly all such methods employ bisulfite-mediated deamination of
      denatured DNA. While this treatment effectively deaminates cytosines to uracils,
      leaving most 5-methylcytosines intact, it also introduces abasic sites that
      generate a significant number of single-strand breaks in DNA. We have
      investigated the interplay of these two processes in order to determine their
      relative effects on the methylation-sensitive QPCR method. The extent of cleavage
      of the input DNA is significant and appears to be an increasing function of DNA
      concentration. Even so, the results suggest that only approximately 10% of a 62
      nt target will be lost due to degradation and targets up to 131 nt will suffer
      only a 20% loss. More significant losses were found to occur during the
      subsequent removal of bisulfite and desulfonation steps that appear to be the
      result of size selectivity associated with matrix binding and elution required
      prior to QPCR in the most commonly used protocols. For biospecimens yielding <1
      microg of DNA, these findings suggest that bisulfite treatment, in current
      implementations of MS-QPCR, result in low recoveries that preclude reliable
      analysis of DNA methylation patterns regardless of target size.

PMID- 17439965
TI  - Specificity, duplex degradation and subcellular localization of antagomirs.
AB  - MicroRNAs (miRNAs) are an abundant class of 20-23-nt long regulators of gene
      expression. The study of miRNA function in mice and potential therapeutic
      approaches largely depend on modified oligonucleotides. We recently demonstrated
      silencing miRNA function in mice using chemically modified and cholesterol
      conjugated RNAs termed 'antagomirs'. Here, we further characterize the properties
      and function of antagomirs in mice. We demonstrate that antagomirs harbor
      optimized phosphorothioate modifications, require >19-nt length for highest
      efficiency and can discriminate between single nucleotide mismatches of the
      targeted miRNA. Degradation of different chemically protected miRNA/antagomir
      duplexes in mouse livers and localization of antagomirs in a cytosolic
      compartment that is distinct from processing (P)-bodies indicates a degradation
      mechanism independent of the RNA interference (RNAi) pathway. Finally, we show
      that antagomirs, although incapable of silencing miRNAs in the central nervous
      system (CNS) when injected systemically, efficiently target miRNAs when injected
      locally into the mouse cortex. Our data further validate the effectiveness of
      antagomirs in vivo and should facilitate future studies to silence miRNAs for
      functional analysis and in clinically relevant settings.

PMID- 17439966
TI  - Wheat Estimated Transcript Server (WhETS): a tool to provide best estimate of
      hexaploid wheat transcript sequence.
AB  - Wheat biologists face particular problems because of the lack of genomic sequence
      and the three homoeologous genomes which give rise to three very similar forms
      for many transcripts. However, over 1.3 million available public-domain Triticeae
      ESTs (of which approximately 850,000 are wheat) and the full rice genomic
      sequence can be used to estimate likely transcript sequences present in any wheat
      cDNA sample to which PCR primers may then be designed. Wheat Estimated Transcript
      Server (WhETS) is designed to do this in a convenient form, and to provide
      information on the number of matching EST and high quality cDNA (hq-cDNA)
      sequences, tissue distribution and likely intron position inferred from rice.
      Triticeae EST and hq-cDNA sequences are mapped onto rice loci and stored in a
      database. The user selects a rice locus (directly or via Arabidopsis) and the
      matching Triticeae sequences are assembled according to user-defined filter and
      stringency settings. Assembly is achieved initially with the CAP3 program and
      then with a single nucleotide polymorphism (SNP)-analysis algorithm designed to
      separate homoeologues. Alignment of the resulting contigs and singlets against
      the rice template sequence is then displayed. Sequences and assembly details are
      available for download in fasta and ace formats, respectively. WhETS is
      accessible at http://www4.rothamsted.bbsrc.ac.uk/whets.

PMID- 17439967
TI  - OPTIMIZER: a web server for optimizing the codon usage of DNA sequences.
AB  - OPTIMIZER is an on-line application that optimizes the codon usage of a gene to
      increase its expression level. Three methods of optimization are available: the
      'one amino acid-one codon' method, a guided random method based on a Monte Carlo
      algorithm, and a new method designed to maximize the optimization with the fewest
      changes in the query sequence. One of the main features of OPTIMIZER is that it
      makes it possible to optimize a DNA sequence using pre-computed codon usage
      tables from a predicted group of highly expressed genes from more than 150
      prokaryotic species under strong translational selection. These groups of highly
      expressed genes have been predicted using a new iterative algorithm. In addition,
      users can use, as a reference set, a pre-computed table containing the mean codon
      usage of ribosomal protein genes and, as a novelty, the tRNA gene-copy numbers.
      OPTIMIZER is accessible free of charge at http://genomes.urv.es/OPTIMIZER.

PMID- 17439968
TI  - RNA polymerase III transcription is repressed in response to the tumour
      suppressor ARF.
AB  - The tumour suppressor protein ARF provides a defence mechanism against
      hyperproliferative stresses that can result from the aberrant activation of
      oncogenes. Accordingly, ARF is silenced or deleted in many human cancers.
      Activation of ARF can arrest growth and cell cycle progression, or trigger
      apoptosis. A principle mediator of these effects is p53, which ARF stabilizes by
      binding and inhibiting MDM2. However, ARF has additional targets and remains able
      to block growth in the absence of p53, albeit less efficiently. For example, ARF
      can suppress rRNA production in a p53-independent manner. We have found that the
      synthesis of tRNA by RNA polymerase III is also inhibited in response to ARF.
      However, in contrast to its effects on rRNA synthesis, ARF is unable to inhibit
      tRNA gene transcription when p53 is ablated. These results add to the growing
      list of cellular changes that can be triggered by ARF induction.

PMID- 17439969
TI  - Mitochondrial diversity within modern human populations.
AB  - With the recent increase in the available number of high-quality, full-length
      mitochondrial sequences, it is now possible to construct and analyze a
      comprehensive human mitochondrial consensus sequence. Using a data set of 827
      carefully selected sequences, it is shown that modern humans contain extremely
      low levels of divergence from the mitochondrial consensus sequence, differing by
      a mere 21.6 nt sites on average. Fully 84.1% of the mitochondrial genome was
      found to be invariant and 'private' mutations accounted for 43.8% of the variable
      sites. Ninety eight percent of the variant sites had a primary nucleotide with an
      allele frequency of 0.90 or greater. Interestingly, the few truly ambiguous
      nucleotide sites could all be reliably assigned to either a purine or pyrimidine
      ancestral state. A comparison of this consensus sequence to several ancestral
      sequences derived from phylogenetic studies reveals a great deal of similarity,
      where, as expected, the most phylogenetically informative nucleotides in the
      ancestral studies tended to be the most variable nucleotides in the consensus.
      Allowing for this fact, the consensus approach provides variation data on the
      positions that do not contribute to phylogenetic reconstructions, and these data
      provide a baseline for measuring human mitochondrial variation in populations
      worldwide.

PMID- 17439970
TI  - The open state of human topoisomerase I as probed by molecular dynamics
      simulation.
AB  - The open state of human topoisomerase I has been probed by molecular dynamics
      simulation, starting from the coordinates of the closed structure of the protein
      complexed with DNA, after elimination of the 22-bp DNA duplex oligonucleotide. A
      repulsion force between the two lips of the protein has been introduced for a
      short time to induce destabilization of the local minimum, after which an
      unperturbed simulation has been carried out for 10 ns. The simulation shows that
      the protein undergoes a large conformational change due to rearrangements in the
      orientation of the protein domains, which however move as a coherent unit, fully
      maintaining their secondary and tertiary structures. Despite movements between
      the domains as large as 80-90 A, the catalytic pentad remains preassembled, the
      largest deviation of the active site backbone atoms from the starting
      crystallographic structure being only 1.7 A. Electrostatic calculation of the
      open protein structure shows that the protein displays a vast positive region
      with the active site residues located nearly at its center, in a conformation
      perfectly suited to interact with the negatively charged supercoiled DNA
      substrate.

PMID- 17439971
TI  - Escherichia coli ribosomal protein L20 binds as a single monomer to its own mRNA
      bearing two potential binding sites.
AB  - Ribosomal protein L20 is crucial for the assembly of the large ribosomal subunit
      and represses the translation of its own mRNA. L20 mRNA carries two L20-binding
      sites, the first folding into a pseudoknot and the second into an imperfect stem
      and loop. These two sites and the L20-binding site on 23S ribosomal RNA are
      recognized similarly using a single RNA-binding site located on one face of L20.
      In this work, using gel filtration and fluorescence cross-correlation
      spectroscopy (FCCS) experiments, we first exclude the possibility that L20 forms
      a dimer, which would allow each monomer to bind one site of the mRNA. Secondly we
      show, using affinity purification and FCCS experiments, that only one molecule of
      L20 binds to the L20 mRNA despite the presence of two potential binding sites.
      Thirdly, using RNA chemical probing, we show that the two L20-binding sites are
      in interaction. This interaction provides an explanation for the single occupancy
      of the mRNA. The two interacting sites could form a single hybrid site or the
      binding of L20 to a first site may inhibit binding to the second. Models of
      regulation compatible with our data are discussed.

PMID- 17439972
TI  - CAF1 plays an important role in mRNA deadenylation separate from its contact to
      CCR4.
AB  - The CAF1 protein is a component of the CCR4-NOT deadenylase complex. While yeast
      CAF1 displays deadenylase activity, this activity is not required for its
      deadenylation function in vivo, and CCR4 is the primary deadenylase in the
      complex. In order to identify CAF1-specific functional regions required for
      deadenylation in vivo, we targeted for mutagenesis six regions of CAF1 that are
      specifically conserved among CAF1 orthologs. Defects in residues 213-215, found
      to be a site required for binding CCR4, reduced the rate of deadenylation to a
      lesser extent and resulted in in vivo phenotypes that were less severe than did
      defects in other regions of CAF1 that displayed greater contact to CCR4. These
      results imply that CAF1, while affecting deadenylation through its contact to
      CCR4, has functions in deadenylation separate from its contact to CCR4. Synthetic
      lethalities of caf1Delta, but not that of ccr4Delta, with defects in DHH1 or
      PAB1, both of which are involved in translation, further supports a role of CAF1
      separate from that of CCR4. Importantly, other mutations in PAB1 that reduced
      translation, while not affecting deadenylation by themselves or when combined
      with ccr4Delta, severely blocked deadenylation when coupled with a caf1 deletion.
      These results indicate that both CAF1 and factors involved in translation are
      required for deadenylation.

PMID- 17439973
TI  - Sequence analysis of p53 response-elements suggests multiple binding modes of the
      p53 tetramer to DNA targets.
AB  - The p53 tetramer recognizes specifically a 20-bp DNA element. Here, we examined
      symmetries encoded in p53 response elements (p53REs). We analyzed base inversion
      correlations within the half-site, as well as in the full-site palindrome. We
      found that p53REs are not only direct repeats of half-sites; rather, two p53 half
      sites couple to form a higher order 20 bp palindrome. The palindrome couplings
      between the half-sites are stronger for the human than for the mouse genome. The
      full-site palindrome and half-site palindrome are controlled by insertions
      between the two half-sites. The most notable feature is that the full-site
      palindrome with coupling between quarter-sites one and four (H14 coupling)
      dominates the p53REs without insertions. The most frequently observed insertion
      in human p53REs of 3 bp enhances the half-site palindrome. The statistical
      frequencies of the coupling between the half-sites in the human genome correlate
      with grouped experimental p53 affinities with p53REs. Examination of known p53REs
      indicates the H14 couplings are stronger for positive regulation than for
      negatively regulated p53REs, with repressors having the lowest H14 couplings. We
      propose that the palindromic sequence couplings may encode such potential
      preferred multiple binding modes of the p53 tetramer to DNA.

PMID- 17439974
TI  - Comparative evaluation of VITEK 2 for antimicrobial susceptibility testing of
      group B Streptococcus.
AB  - OBJECTIVES: Intrapartum antibiotic prophylaxis is recommended to prevent neonatal
      group B streptococcal (GBS) disease in colonized women, and penicillin or
      aminopenicillin constitute the first-line antibiotics. Most isolates are
      resistant to tetracycline, and resistance to macrolide-lincosamide-streptogramin
      (MLS) antibiotics is increasing. Therefore, laboratory testing for MLS resistance
      in GBS is now recommended for penicillin-allergic patients. The aim of this study
      was to compare the antimicrobial susceptibility of GBS as determined by the VITEK
      2 system (bioMerieux, Marcy l'Etoile, France), agar diffusion methods and PCR
      genotypic detection of resistance genes. METHODS: One hundred and ten unrelated
      selected GBS clinical isolates were studied. The antibiotics tested (VITEK 2 and
      agar diffusion method) were benzylpenicillin, ampicillin, erythromycin,
      clindamycin, co-trimoxazole, tetracycline, kanamycin, streptomycin and
      vancomycin. A standardized double-disc (DD) diffusion test was performed for MLS
      antibiotics. Genotypic characterization of tetracycline, MLS and aminoglycoside
      resistance genes was performed by PCR. RESULTS: All strains were susceptible to
      benzylpenicillin, ampicillin and vancomycin [category agreement (CA) between
      VITEK 2 and the diffusion method was 100%]. Ninety-five (86%) strains were
      resistant to tetracycline (CA was 98.9%). Eighty-one strains (73.6%) harboured an
      MLS resistance phenotype; 50 (61.8%) an MLS(B)-constitutive phenotype, 25 (30.8%)
      an MLS(B)-inducible phenotype and 6 (7.4%) an M phenotype. The agreement between
      data of VITEK 2 and the DD diffusion test for the detection of MLS(B)
      constitutive, MLS(B)-inducible and M phenotype isolates was 76%, 36% and 100%,
      respectively. Almost all discrepancies were due to failure to detect erythromycin
      resistance by VITEK 2. CONCLUSIONS: VITEK 2 allows accurate determination of GBS
      susceptibility for the majority of antibiotics, but has to be improved for
      erythromycin. Thus, the DD diffusion test remains the most simple and reliable
      method for macrolide resistance detection among this streptococcal species.

PMID- 17439975
TI  - Evaluation of amino acids as mediators for the antibacterial activity of iodine
      lithium-alpha-dextrin in vitro and in vivo.
AB  - OBJECTIVES: The systemic therapeutic application of iodophores has not yet been
      accepted due to limited availability of safe and effective ionized iodine
      preparations. Here we evaluated the antibacterial activity of iodine-lithium
      alpha-dextrin (ILalphaD) both in vitro and in vivo. METHODS: The MIC values of
      ILalphaD against 189 bacterial isolates in various growth media and in vivo
      toxicity and protective efficacy of ILalphaD in preventing mortality of rats
      infected with Staphylococcus aureus were determined. The intracellular killing of
      S. aureus by neutrophils in the presence of ILalphaD and myeloperoxidase (MPO)
      catalysed oxidation of iodide was also determined. RESULTS: The MIC values of
      ILalphaD against 189 Gram-positive cocci and Gram-negative bacilli ranged between
      124-512 mg/L in growth media and 6.2-12.5 mg/L in buffer solution, and were
      highly variable in the presence of amino acids. We observed protection of S.
      aureus-infected rats from death with significant reduction of bacterial growth in
      organs upon intravenous administration of ILalphaD at doses that are 4-12 times
      lower than maximal in vivo tolerability dose. Intracellular killing of S. aureus
      by neutrophils increased in the presence of ILalphaD probably due to MPO
      catalysed oxidation of iodide into hypoiodous acid. The pattern of ILalphaD
      reaction with amino acids at different pH or halide ion content determined both
      the generation of long-lived secondary oxidants and antibacterial activity.
      CONCLUSIONS: Systemic application of ILalphaD proved to be successful in the rat
      infection model by promoting host defence. Probable mechanisms are increased
      intracellular killing of bacteria by production of hypoiodous acid and iodamines
      as well as anti-inflammatory activity.

PMID- 17439976
TI  - Low-level exposure of MRSA to octenidine dihydrochloride does not select for
      resistance.

PMID- 17439977
TI  - A trial of immunotherapy against Leishmania amazonensis infection in vitro and in
      vivo with Z-100, a polysaccharide obtained from Mycobacterium tuberculosis, alone
      or combined with meglumine antimoniate.
AB  - OBJECTIVES: To determine the efficacy and the immunomodulatory function of Z-100
      alone or combined with meglumine antimoniate on Leishmania amazonensis infection.
      METHODS: The effect of the compounds was evaluated by microscopic counting of
      intracellular amastigotes in macrophages stained with Giemsa, or axenic
      promastigotes, and IC(50) was determined by linear regression. The
      antileishmanial effect of the compounds was assessed in infected BALB/c mice by a
      limiting dilution analysis and the production of gamma interferon (IFN-gamma),
      interleukin 10 (IL-10), IL-4, IgG1 and IgG2a was measured by ELISA. RESULTS: In
      vitro, Z-100 showed antileishmanial activity against intracellular amastigotes of
      L. amazonensis with an IC(50) of 13 mg/L. Moreover, infected macrophages treated
      with Z-100 (12 mg/L) showed smaller parasitophorous vacuoles with fewer parasites
      than the control. In addition, the efficacy of Z-100 plus meglumine antimoniate
      [14 mg/L pentavalent antimony (Sb(v))] was higher (46% inhibition) than either Z
      100 or meglumine antimoniate alone. Nevertheless, no effect of Z-100 on axenic
      promastigotes was observed. Infected BALB/c mice treated with Z-100 (100
      microg/kg) alone did not show any antileishmanial effects in comparison with the
      control group, and IFN-gamma, as well as IL-10 and IL-4, was up-regulated by the
      treatment. In addition, both IgG1 and IgG2a were also increased by the Z-100
      treatment. Although Z-100 plus meglumine antimoniate (14 or 28 mg/kg Sb(v))
      controlled both the parasite load and the footpad swelling in comparison with
      control mice, no significant differences were found with meglumine antimoniate
      alone. CONCLUSIONS: In vitro, Z-100 alone or combined with meglumine antimoniate
      showed an antileishmanial effect on L. amazonensis. However, no effect was
      observed in infected BALB/c mice treated with Z-100, suggesting that the up
      regulation of IL-10 and IL-4 production by the treatment could be interfering
      with the development of a protective Th1-type response. For further understanding
      of the effects of Z-100 in vivo, another strain of mice such as C57BL/6 should be
      tested in future.

PMID- 17439978
TI  - The prevalence of physician self-referral arrangements after Stark II: evidence
      from advanced diagnostic imaging.
AB  - Using data from a large insurer in California, we identified the self-referral
      status of providers who billed for advanced imaging in 2004. Nearly 33 percent of
      providers who submitted bills for magnetic resonance imaging (MRI) scans, 22
      percent of those who submitted bills for computed tomography (CT) scans, and 17
      percent of those who submitted bills for positron-emission tomography (PET) scans
      were classified as "self-referral." Among them, 61 percent of those who billed
      for MRI and 64 percent of those who billed for CT did not own the imaging
      equipment. Rather, they were involved in lease or payment-per-scan referral
      arrangements that might violate federal and state laws.

PMID- 17439979
TI  - Kinematic analysis of thalamic versus subthalamic neurostimulation in postural
      and intention tremor.
AB  - Deep brain stimulation of the thalamus (thalamic DBS) is an established therapy
      for medically intractable essential tremor and tremor caused by multiple
      sclerosis. In both disorders, motor disability results from complex interaction
      between kinetic tremor and accompanying ataxia with voluntary movements. In
      clinical studies, the efficacy of thalamic DBS has been thoroughly assessed.
      However, the optimal anatomical target structure for neurostimulation is still
      debated and has never been analysed in conjunction with objective measurements of
      the different aspects of motor impairment. In 10 essential tremor and 11 multiple
      sclerosis patients, we analysed the effect of thalamic DBS through each contact
      of the quadripolar electrode on the contralateral tremor rating scale,
      accelerometry and kinematic measures of reach-to-grasp-movements. These measures
      were correlated with the anatomical position of the stimulating electrode in
      stereotactic space and in relation to nuclear boundaries derived from
      intraoperative microrecording. We found a significant impact of the stereotactic
      z-coordinate of stimulation contacts on the TRS, accelerometry total power and
      spatial deviation in the deceleration and target period of reach-to-grasp
      movements. Most effective contacts clustered within the subthalamic area (STA)
      covering the posterior Zona incerta and prelemniscal radiation. Stimulation
      within this region led to a mean reduction of the lateralized tremor rating scale
      by 15.8 points which was significantly superior to stimulation within the
      thalamus (P < 0.05, student's t-test). STA stimulation resulted in reduction of
      the accelerometry total power by 99%, whereas stimulation at the ventral thalamic
      border (68%) or within the thalamus proper (2.5%) was significantly less
      effective (P < 0.01). Concomitantly, STA stimulation led to a significantly
      higher increase of tremor frequency and decrease in EMG synchronization compared
      to stimulation within the thalamus proper (P < 0.001). In reach-to-grasp
      movements, STA stimulation reduced the spatial variability of the movement path
      in the deceleration period by 28.9% and in the target period by 58.4%, whereas
      stimulation within the thalamus was again significantly less effective (P <
      0.05), with a reduction in the deceleration period between 6.5 and 21.8% and in
      the target period between 1.2 and 11.3%. An analysis of the nuclear boundaries
      from intraoperative microrecording confirmed the anatomical impression that most
      effective electrodes were located within the STA. Our data demonstrate a profound
      effect of deep brain stimulation of the thalamic region on tremor and ataxia in
      essential tremor and tremor caused by multiple sclerosis. The better efficacy of
      stimulation within the STA compared to thalamus proper favours the concept of a
      modulation of cerebello-thalamic projections underlying the improvement of these
      symptoms.

PMID- 17439980
TI  - A novel progranulin mutation associated with variable clinical presentation and
      tau, TDP43 and alpha-synuclein pathology.
AB  - Mutations in the progranulin (GRN) gene have recently been reported as a cause of
      the frontotemporal dementia (FTD) syndrome. We performed a clinical,
      neuropathological and molecular genetic study of two families with FTD and the
      same novel mutation in GRN. Age of onset ranged from 35 to 75 years and all
      individuals progressed to a severe dementia syndrome with a mean disease duration
      of approximately 6-10 years. Variable clinical presentations included language
      impairment, behaviour change or parkinsonism. Seven total autopsies in the
      families (five in Family 1, two in Family 2) showed gross and microscopic
      evidence of neuronal loss in the neocortex, striatum, hippocampus and substantia
      nigra. All cases with material available for immunohistochemistry had cytoplasmic
      and intranuclear ubiquitin positive, tau negative inclusions that stained best
      with an antibody to the TDP43 protein. In addition, all but one had evidence of
      distinctive tau pathology. Two cases in Family 1 also had alpha-synuclein (SNCA)
      pathology, one with diffuse neocortical inclusions and neurites and unusual
      striatal cytoplasmic inclusions. Affected persons in both families had the same
      mutation in GRN (c.709-2A>G). A minigene construct showed that this mutation
      alters splicing of exon 7 and results in reduced mRNA message in brain. A single
      GRN mutation in these two families was associated with variable clinical
      presentations consistent with the FTD syndrome. All cases had ubiquitin/TDP43
      immuno-positive inclusions and most had additional tau pathology. Two cases had
      SNCA pathology. These findings suggest a link between mutations in GRN and
      aggregation of tau, TDP43 and SNCA.

PMID- 17439981
TI  - Phenotypical spectrum of DOK7 mutations in congenital myasthenic syndromes.
AB  - Dok ('downstream-of-kinase') family of cytoplasmic proteins play a role in
      signalling downstream of receptor and non-receptor phosphotyrosine kinases.
      Recently, a skeletal muscle receptor tyrosine kinase (MuSK)-interacting
      cytoplasmic protein termed Dok-7 has been identified. Subsequently, we and others
      identified mutations in DOK7 as a cause of congenital myasthenic syndromes (CMS),
      providing evidence for a crucial role of Dok-7 in maintaining synaptic structure.
      Here we present clinical and molecular genetic data of 14 patients from 12
      independent kinships with 13 different mutations in the DOK7 gene. The clinical
      picture of CMS with DOK7 mutations is highly variable. The age of onset may vary
      between birth and the third decade. However, most of the patients display a
      characteristic 'limb-girdle' pattern of weakness with a waddling gait and ptosis,
      but without ophthalmoparesis. Respiratory problems were frequent. Patients did
      not benefit from long-term therapy with esterase inhibitors; some of the patients
      even worsened. DOK7 mutations have emerged as one of the major genetic defects in
      CMS. The clinical picture differs significantly from CMS caused by mutations in
      other genes, such as the acetylcholine receptor (AChR) subunit genes. None of the
      patients with DOK7 mutations had tubular aggregates in the muscle biopsy,
      implying that 'limb-girdle myasthenia (LGM) with tubular aggregates' previously
      described in literature may be a pathogenic entity distinct from CMS caused by
      DOK7 mutations.

PMID- 17439982
TI  - Chronic progressive ophthalmoplegia with large-scale mtDNA rearrangement: can we
      predict progression?
AB  - The prognosis of chronic progressive ophthalmoplegia with large-scale
      mitochondrial DNA (mtDNA) may strikingly vary from mild slowly progressive
      myopathy to severe multi-organ involvement. Evaluation of the disease course at
      the beginning of the disease is reputed impossible. To address the existence of
      predictive prognostic clues of these diseases, we classified 69 patients with
      chronic progressive ophthalmoplegia and large size mtDNA deletion into two groups
      according to the presence of manifestations from brain, inner ear or retina.
      These manifestations were present in 29 patients (CPEO/+N group) and absent in 40
      patients (CPEO/-N group). We retrospectively established the clinical history of
      the patients and characterized their genetic alteration (amount of residual
      normal mtDNA molecules, site, size and percentage of the mtDNA deletion in 116
      DNA samples from muscle, blood, urinary and buccal cells). In both clinical
      groups, the disease was progressive and heart conduction defects were frequent.
      We show that the CPEO/+N phenotype segregated with severe prognosis in term of
      rate of progression, multi-organs involvement and rate of survival. Age at onset
      appeared a predictive factor. The risk to develop a CPEO/+N phenotype was high
      when onset was before 9 years of age and low when onset was after 20 years of
      age. The presence and proportion of the mtDNA deletion in blood was also
      significantly associated with the CPEO/+N phenotype. This study is the first to
      establish the natural history of chronic ophthalmoplegia with mtDNA deletion in a
      large series of patients and to look for parameters potentially predictive of the
      patients' clinical course.

PMID- 17439983
TI  - TDP-43 is deposited in the Guam parkinsonism-dementia complex brains.
AB  - TDP-43, a nuclear factor that functions in regulating transcription and
      alternative splicing, was recently identified as a component of the ubiquitin
      positive, tau-negative inclusions specific for frontotemporal lobar degeneration
      (FTLD-U) and amyotrophic lateral sclerosis (ALS). In the present study, we
      carried out immunohistochemical and biochemical analyses of brains of Guamanians
      with the parkinsonism-dementia complex (G-PDC) using anti-TDP-43, anti-tau and
      anti-ubiquitin antibodies. Immunohistochemistry with anti-TDP-43 antibodies
      revealed various types of positive structures in the frontotemporal and
      hippocampal regions of G-PDC cases. Most of these structures were negative for
      tau. By immunoblot analysis with the TDP-43 antibody, an abnormal 45 kDa band, as
      well as a diffuse staining throughout the gel, was detected in the sarkosyl
      insoluble fractions of G-PDC brains. Dephosphorylation has shown that abnormal
      phosphorylation takes place in the accumulated TDP-43 seen in FTLD-U and ALS.
      These results suggest that accumulation of TDP-43 is a common process in certain
      neurodegenerative disorders, including FTLD-U, ALS and G-PDC.

PMID- 17439984
TI  - Modification of the number and phenotype of striatal dopaminergic cells by
      carotid body graft.
AB  - In non-human primates, striatal tyrosine hydroxylase-immunoreactive (TH-ir) cells
      are increased in number after dopamine depletion and in response to trophic
      factor delivery. As carotid body cells contain the dopaminotrophic glial cell
      line-derived neurotrophic factor (GDNF), we evaluated the number, morphology and
      neurochemistry of these TH-ir cells, in the anterior and posterior striatum of
      five monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      which received a graft of carotid body cell aggregates (CBCA) (n = 3) or sham
      surgery (n = 2), and six MPTP-monkeys that were sacrificed 6 months and 3 years
      after the last MPTP dose [MPTP I (n = 3) and MPTP II (n = 3), respectively].
      Three intact monkeys served as controls. A disability rating scale was used for
      the assessment of parkinsonism in all lesioned animals, both before and after
      surgery. For the neurochemical examination, tissue sections were double-labelled
      with antibodies to TH, dopamine transporter, dopa decarboxylase-67, vesicular
      monoamine transporter 2, glutamic acid decarboxylase -67, calbindin, parvalbumin,
      calretinin, neuronal nitric oxide synthase and GDNF. Only animals receiving CBCA
      graft showed a moderate but significant recovery of parkinsonism that persisted
      12 months after the graft. The grafted striatum contained the greatest TH-ir cell
      density (120.4 +/- 10.3 cells/100 mm2), while the control striatum displayed the
      lowest (15.4 +/- 6.8 cells/100 mm2), and MPTP I, MPTP II and sham-operated
      monkeys showed a similar intermediate value (66.1 +/- 6.2, 58.3 +/- 17.2 and 57.7
      +/- 7.0 cells/100 mm2, respectively). In addition, in the post-commissural
      striatum, only CBCA graft induced a significant increase in the TH-ir cell
      density compared to control animals (47.9 +/- 15.9 and 7.9 +/- 3.2,
      respectively). Phenotypically, TH-ir cells were striatal dopaminergic
      interneurons. However, in the grafted animals, the phenotype was different from
      that in control, MPTP and sham-operated monkeys, with the appearance of TH/GDNF
      ir cells and the emergence of two TH-ir subpopulations of different size as the
      two main differentiating features. Our data confirm and extend previous studies
      demonstrating that striatal CBCA grafts produce a long-lasting motor recovery of
      MPTP-monkeys along with an increase in the number and phenotype changes of the
      striatal TH-ir interneurons, probably by the action of the trophic factors
      contained in carotid body cells. The increased number of striatal TH-ir cells
      observed in the grafted striatum may contribute to the improvement of
      parkinsonism observed after the graft.

PMID- 17439985
TI  - Large-scale pathways-based association study in amyotrophic lateral sclerosis.
AB  - Sporadic amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative
      disease, most likely results from complex genetic and environmental interactions.
      Although a number of association studies have been performed in an effort to find
      genetic components of sporadic ALS, most of them resulted in inconsistent
      findings due to a small number of genes investigated in relatively small sample
      sizes, while the replication of results was rarely attempted. Defects in
      retrograde axonal transport, vesicle trafficking and xenobiotic metabolism have
      been implicated in neurodegeneration and motor neuron death both in human disease
      and animal models. To assess the role of common genetic variation in these
      pathways in susceptibility to sporadic ALS, we performed a pathway-based
      candidate gene case-control association study with replication. Furthermore, we
      determined reliability of whole genome amplified DNA in a large-scale association
      study. In the first stage of the study, 1277 putative functional and tagging SNPs
      in 134 genes spanning 8.7 Mb were genotyped in 822 British sporadic ALS patients
      and 872 controls using whole genome amplified DNA. To detect variants with modest
      effect size and discriminate among false positive findings 19 SNPs showing a
      trend of association in the initial screen were genotyped in a replication sample
      of 580 German sporadic ALS patients and 361 controls. We did not detect strong
      evidence of association with any of the genes investigated in the discovery
      sample (lowest uncorrected P-value 0.00037, lowest permutation corrected P-value
      0.353). None of the suggestive associations was replicated in a second sample,
      further excluding variants with moderate effect size. We conclude that common
      variation in the investigated pathways is unlikely to have a major effect on
      susceptibility to sporadic ALS. The genotyping efficiency was only slightly
      decreased ( approximately 1%) and genotyping quality was not affected using whole
      genome amplified DNA. It is reliable for large scale genotyping studies of
      diseases such as ALS, where DNA sample collections are limited because of low
      disease prevalence and short survival time.

PMID- 17439986
TI  - Neural stem cells LewisX+ CXCR4+ modify disease progression in an amyotrophic
      lateral sclerosis model.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized
      by the degeneration of the motor neurons. We tested whether treatment of
      superoxide dismutase (SOD1)-G93A transgenic mouse, a model of ALS, with a neural
      stem cell subpopulation double positive for Lewis X and the chemokine receptor
      CXCR4 (LeX+CXCR4+) can modify the disease's progression. In vitro, after exposure
      to morphogenetic stimuli, LeX+CXCR4+ cells generate cholinergic motor neuron-like
      cells upon differentiation. LeX+CXCR4+ cells deriving from mice expressing Green
      Fluorescent Protein in all tissues or only in motor neurons, after a period of
      priming in vitro, were grafted into spinal cord of SOD1-G93A mice. Transplanted
      transgenic mice exhibited a delayed disease onset and progression, and survived
      significantly longer than non-treated animals by 23 days. Examination of the
      spinal cord revealed integration of donor-derived cells that differentiated
      mostly in neurons and in a lower proportion in motor neuron-like cells.
      Quantification of motor neurons of the spinal cord suggests a significant
      neuroprotection by LeX+CXCR4+ cells. Both VEGF- and IGF1-dependent pathways were
      significantly modulated in transplanted animals compared to controls, suggesting
      a role of these neurotrophins in MN protection. Our results support the
      therapeutic potential of neural stem cell fractions through both neurogenesis and
      growth factors release in motor neuron disorders.

PMID- 17439987
TI  - Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult
      onset, dominant myopathies are associated with the desmin mutation R350P.
AB  - In 1965, an adult-onset, autosomal dominant disorder with a peculiar
      scapuloperoneal distribution of weakness and atrophy was described in a large,
      multi-generation kindred and named 'scapuloperoneal syndrome type Kaeser' (OMIM
      #181400). By genetic analysis of the original kindred, we discovered a
      heterozygous missense mutation of the desmin gene (R350P) cosegregating with the
      disorder. Moreover, we detected DES R350P in four unrelated German families
      allowing for genotype-phenotype correlations in a total of 15 patients carrying
      the same mutation. Large clinical variability was recognized, even within the
      same family, ranging from scapuloperoneal (n = 2, 12%), limb girdle (n = 10, 60%)
      and distal phenotypes (n = 3, 18%) with variable cardiac (n = 7, 41%) or
      respiratory involvement (n = 7, 41%). Facial weakness, dysphagia and
      gynaecomastia were frequent additional symptoms. Overall and within each family,
      affected men seemingly bear a higher risk of sudden, cardiac death as compared to
      affected women. Moreover, histological and immunohistochemical examination of
      muscle biopsy specimens revealed a wide spectrum of findings ranging from near
      normal or unspecific pathology to typical, myofibrillar changes with accumulation
      of desmin. This study reveals that the clinical and pathological variability
      generally observed in desminopathies may not be attributed to the nature of the
      DES mutation alone, but may be influenced by additional genetic and epigenetic
      factors such as gender. In addition, mutations of the desmin gene should be
      considered early in the diagnostic work-up of any adult-onset, dominant myopathy,
      even if specific myofibrillar pathology is absent.

PMID- 17439988
TI  - Heterogeneity of aquaporin-4 autoimmunity and spinal cord lesions in multiple
      sclerosis in Japanese.
AB  - Opticospinal multiple sclerosis (OSMS) in Asians has similar features to the
      relapsing-remitting form of neuromyelitis optica (NMO) seen in Westerners. OSMS
      is suggested to be NMO based on the frequent detection of specific IgG targeting
      aquaporin-4 (AQP4), designated NMO-IgG. The present study sought to clarify the
      significance of anti-AQP4 autoimmunity in the whole spectrum of MS. Sera from 113
      consecutive Japanese patients with clinically definite MS, based on the Poser
      criteria, were assayed for anti-AQP4 antibodies by immunofluorescence using GFP
      AQP4 fusion protein-transfected HEK-293T cells. Sensitivity and specificity of
      the anti-AQP4 antibody assay, 83.3 and 100%, respectively, were calculated using
      serum samples with NMO-IgG status predetermined at the Mayo Clinic. The anti-AQP4
      antibody positivity rate was significantly higher in OSMS patients (13/48, 27.1%)
      than those with CMS (3/54, 5.6%), other neurological diseases (0/52) or healthy
      controls (0/35). None of the 11 patients tested with a brainstem-spinal form of
      MS were positive. Among OSMS patients, the antibody positivity rate was highest
      in OSMS patients with longitudinally extensive spinal cord lesions (LESCLs)
      extending over three vertebral segments and brain lesions that fulfilled the
      Barkhof criteria (5/9, 55.6%). Multiple logistic analyses revealed that emergence
      of the anti-AQP4 antibody was positively associated only with a higher relapse
      rate, but not with optic-spinal presentation or LESCLs. Compared with anti-AQP4
      antibody-negative CMS patients, anti-AQP4 antibody-positive MS patients showed
      significantly higher frequencies of severe optic neuritis, acute transverse
      myelitis and LESCLs while most conditions were also common to anti-AQP4 antibody
      negative OSMS patients. The LESCLs in anti-AQP4 antibody-positive patients were
      located at the upper-to-middle thoracic cord, while those in anti-AQP4 antibody
      negative OSMS patients appeared throughout the cervical-to-thoracic cord. On
      axial planes, the former most frequently showed central grey matter involvement,
      while holocord involvement was predominant in the latter. In contrast, LESCLs in
      anti-AQP4 antibody-negative CMS patients preferentially involved the mid-cervical
      cord presenting a peripheral white matter-predominant pattern, as seen in the
      short lesions. Anti-AQP4 antibody-positive MS patients fulfilling definite NMO
      criteria showed female preponderance, higher relapse rate, greater frequency of
      brain lesions and less frequent responses to interferon beta-1b than anti-AQP4
      antibody-negative OSMS patients with LESCLs. These findings suggested that LESCLs
      are distinct in anti-AQP4 antibody positivity and clinical phenotypes. There were
      cases of anti-AQP4 antibody-positive MS/NMO distinct from CMS, and anti-AQP4
      antibody-negative OSMS with LESCLs in Japanese. This indicated that the
      mechanisms producing LESCLs are also heterogeneous in cases with optic-spinal
      presentation, namely AQP4 autoimmunity-related and -unrelated.

PMID- 17439989
TI  - Impaired verbal associative learning after resection of left perirhinal cortex.
AB  - Some patients considered for left temporal lobectomy for epilepsy present with
      normal verbal learning and no MRI evidence of hippocampal pathology. In order to
      preserve learning function, the surgical approach in these cases often aims at
      sparing the hippocampus. Parahippocampal structures, including the left
      perirhinal region, however, also appear to contribute to some forms of verbal
      learning. We studied aspects of verbal learning in four patients with left
      temporal lobe resections that preserved the hippocampus, but which included
      perirhinal/entorhinal cortices in two cases. Pre- and postoperative T1-weighted
      MRI scans were spatially normalized and residual mesial temporal structures
      identified. The two patients whose resection included perirhinal and entorhinal
      cortices exhibited a marked decrement in the ability to acquire arbitrarily
      related word pairs that persisted at 12-month follow-up. Word list learning
      showed an early postoperative impairment, but recovered to normal levels within
      12 months. In two patients, resection encompassed anterolateral and inferior
      temporal neocortex but spared the perirhinal and entorhinal cortices, amygdala
      and hippocampus. No postoperative change in verbal learning was evident. We
      concluded that hippocampal-sparing left temporal lobe resections result in task
      specific verbal learning deficits when perirhinal/entorhinal tissue is included
      in the resection.

PMID- 17439990
TI  - Barriers to clinical risk scores adoption.

PMID- 17439992
TI  - 'Dying twice': a multi-level model of the roots of AIDS stigma in two South
      African communities.
AB  - We highlight the complex interplay of psychological and social factors driving
      AIDS stigma, drawing on a study of community responses to HIV/AIDS in two
      communities in KwaZulu-Natal, South Africa. We draw on 120 semi-structured
      interviews and focus groups, in which open-ended topic guides were used to
      explore community responses to HIV/AIDS. Drivers of stigma included fear; the
      availability and relevance of AIDS-related information; the lack of social spaces
      to engage in dialogue about HIV/AIDS; the link between HIV/AIDS, sexual
      moralities and the control of women and young people; the lack of adequate
      HIV/AIDS management services; and the way in which poverty shaped people's
      reactions to HIV/AIDS. We discuss the implications of our findings for stigma
      reduction programmes.

PMID- 17439994
TI  - Epilepsy, culture, identity and well-being: a study of the social, cultural and
      environmental context of epilepsy in Cameroon.
AB  - Epilepsy presents an identity of exclusion, which at multiple levels hinders the
      ability to engage with one's community. This article describes an exploratory,
      mixed methods study (N = 42) of the relationship between the social, cultural and
      environmental context and the experience of living with epilepsy in Cameroon.
      Participants were identified as 'epileptics', consequently restrictions placed on
      them reduced their ability to perform traditional roles, affected their social
      value and excluded them from their communities. Participants detail the effects
      of their reduced 'social value' and the challenges they face in attempts to be re
      integrated as productive and functioning members of society.

PMID- 17439995
TI  - Treatment adherence among primary care patients in a historically disadvantaged
      community in South Africa: a qualitative study.
AB  - The present study examined the issue of treatment adherence among a sample of 23
      rural South African patients living with either hypertension or diabetes, or
      both. The sample was asked to participate in qualitative interviews that asked
      about various aspects of their experience of their illness and treatment. The
      analysis of the data focused on the content of participants' concerns and
      difficulties with adhering to treatment recommendations. The themes that emerged
      from the study were participants' attribution of the origin of their illness,
      their subjective experience of their illness, their concerns about the
      consequences of poor adherence, financial problems and psychosocial support.

PMID- 17439993
TI  - Assessing developmental outcomes in children from Kilifi, Kenya, following
      prophylaxis for seizures in cerebral malaria.
AB  - The purpose of the study was to develop a culture-informed measure of
      developmental outcome and to apply it to detect differences in developmental
      level between children with cerebral malaria enrolled in a clinical trial to
      control seizures during the acute phase of the illness. The instrument was
      administered to a sample of 180 children, three and 12 months after discharge
      from hospital. The measure demonstrated high internal consistency, good inter
      observer reliability, age sensitivity and strong relations with parental report
      of child functioning. No association was found between performance, or change in
      performance, with the prophylactic regime administered. The results suggested
      that the use of Phenobarbital in controlling provoked seizures has no observable
      effect on cognitive function.

PMID- 17439996
TI  - The prevalence of chronic fatigue syndrome in Nigeria.
AB  - The present study found adult rates of chronic fatigue syndrome (CFS) in Nigeria
      that were somewhat higher than rates from community-based CFS epidemiologic
      studies in the USA. The rates of chronic fatigue for both adults and children
      were also higher than in existing community-based studies. It is possible that
      the presence of several fatiguing illnesses such as malaria and typhoid, the lack
      of adequate healthcare resources and poverty in Nigeria, place individuals at
      greater risk for fatigue and its syndromes. There is a need for more
      epidemiologic studies on the prevalence and sociodemographic characteristics of
      CFS in developing countries.

PMID- 17439997
TI  - HIV/AIDS support and African pentecostalism: the case of the Redeemed Christian
      Church of God (RCCG).
AB  - International and African discourses on the HIV/AIDS pandemic and intervention
      neglect the role of religion and religious organizations. Social science
      perspectives in tackling health and disease neglect religious doctrines and faith
      central to worldviews and praxis of religious groups. Both aspects are important
      for religious groups and individuals affected by HIV/AIDS. Informed by a
      religious studies paradigm and through the religious ethnography of the Redeemed
      Christian Church of God (RCCG) in Nigeria and the Diaspora, this article
      demonstrates mechanisms employed by African Pentecostals to combat the epidemic
      and provide support for infected members. The RCCG conceptualization of disease
      and healing is central to understanding responses and measures in combating
      HIV/AIDS.

PMID- 17439998
TI  - Emergency conflict-related psychosocial interventions in Sierra Leone and Uganda:
      lessons from Medecins Sans Frontieres.
AB  - Medecins Sans Frontieres has been involved in emergency mental health or
      psychosocial programmes since 1990. In this article the intervention model
      developed for emergency settings is shared. Psychosocial programmes distinguish
      two elements. The 'psycho'-component facilitates the reconnection of the affected
      individual to his environment. The 'socio'-element aims to create an environment
      that facilitates the individual to re-integrate. The nature of mental health and
      psychosocial programmes requires a multidisciplinary approach. Emotional support
      can also be provided by regular medical staff and does not always require a
      specialist. The years ahead of us are important for the development of
      psychosocial interventions. Fundamental issues such as programme evaluation need
      systematic research.

PMID- 17439999
TI  - Integrating mental health into post-conflict rehabilitation: the case of Sierra
      Leonean and Liberian 'child soldiers'.
AB  - This report discusses the relationship between mental health care and post
      conflict rehabilitation in Sierra Leone and Liberia. Data were collected during
      the author's involvement in mental health programmes for extremely distressed so
      called 'child soldiers' in both countries, as well as involvement in co
      ordinating and supporting professionals in charge of the war-affected population.
      Analysis suggested that mental health was neglected. However consideration of
      mental health is crucial to rehabilitation efforts because it facilitates
      understanding and appropriate responses to the difficulties encountered by both
      professionals and demobilized youth, and needs to be incorporated into designing
      policy, training and interventions.

PMID- 17440000
TI  - Mental health policy development and implementation in four African countries.
AB  - The purpose of the research programme introduced in this article is to provide
      new knowledge regarding comprehensive multisectoral approaches to breaking the
      negative cycle of poverty and mental ill-health. The programme undertakes an
      analysis of existing mental health policies in four African countries (Ghana,
      South Africa, Uganda, Zambia), and will carry out and evaluate interventions to
      assist in the development and implementation of mental health policies in those
      countries, over a five-year period. The four countries in which the programme is
      being conducted represent a variety of scenarios in mental health policy
      development and implementation.

PMID- 17440001
TI  - Equity, empowerment and choice: from theory to practice in public health.
AB  - The purpose of this article is to illustrate how a framework that links equity
      and empowerment to improved health outcomes for those who live in poverty can be
      a useful tool for planning and managing health programmes. Using the work of
      Amartya Sen, Susan Rifkin has developed a framework described in the acronym
      CHOICE. The article applies the framework to two case studies from Kenya seeking
      to reduce the disease burdens of malaria and HIV/AIDS. The article examines how
      the process of pursuing equity and empowerment either supports the positive
      health outcomes identified as objectives and/or strengthens these outcomes.

PMID- 17440002
TI  - The politics of behavioural change for environmental health promotion in
      developing countries.
AB  - Behavioural change remains a popular intervention strategy for environmental
      health promotion in developing countries. This article explores the question of
      why behavioural change interventions continue to be widely used as an
      intervention strategy in developing countries and highlights the political
      implications of this approach. It suggests that framing interventions within a
      mainstream environmental health science paradigm serves to perpetuate a
      behavioural intervention approach while foreclosing other options. It also serves
      to perpetuate sexist representations of poor African women; absolves decision
      makers from addressing broader socio-political concerns (such as poverty and
      inequality) that are key to addressing environmental health concerns in
      developing countries; and sets up an expert model for environmental health and
      behavioural health scientists to thrive.

PMID- 17440003
TI  - Health psychology in African settings: a cultural-psychological analysis.
AB  - African settings provide an important context in which to examine the
      relationship between cultural beliefs and health. First, research in African
      settings helps illuminate the sociocultural grounding of health and illness: the
      idea that beliefs play a constitutive role in the experience of distress. Second,
      research in African settings helps to illuminate the cultural grounding of health
      sciences: the idea that theory and practice reflect particular constructions of
      reality. We examine these ideas in the context of three research examples: the
      prominent experience of personal enemies; epidemic outbreaks of genital-shrinking
      panic; and fears about sabotage of vaccines in immunization campaigns.

PMID- 17440004
TI  - ST segment elevation and chest pain during cryoablation of atrial flutter.
AB  - A 61-year-old male was treated with cryoablation for typical atrial flutter.
      Cryoablation was performed percutaneously with an 8-mm tip catheter to achieve a
      bidirectional conduction block of the cavo-tricuspid isthmus. When freezing at
      the point where bidirectional isthmus block occurred, the patient experienced
      chest pain and ECG showed ST segment elevations corresponding to the right
      coronary artery. Cryoablation may be painless per se, but patients should be told
      to report chest discomfort and surface ECG must be followed carefully during
      ablation.

PMID- 17440005
TI  - Reduction of ventricular tachyarrhythmia by treatment of atrial fibrillation in
      ICD patients with dual-chamber implantable cardioverter/defibrillators capable of
      atrial therapy delivery: the REVERT-AF Study.
AB  - AIMS: The purpose of this prospective, randomized, multicentre study was to
      investigate whether the incidence of ventricular tachyarrhythmia can be reduced
      in standard implantable cardioverter/defibrillator (ICD) patients by implanting a
      dual-chamber ICD capable of atrial therapy delivery. METHODS AND RESULTS: A Jewel
      AF or GEM III AT ICD (Medtronic Inc., Minneapolis, MN, USA) was implanted in 122
      patients (62.3 +/- 10.5 years; 84.4% male; coronary artery disease 71.3%; left
      ventricular ejection fraction 39.7 +/- 13.6%; secondary ICD indication 91%).
      Overall, 31.2% of the patients had paroxysmal atrial fibrillation (AF)/atrial
      tachycardia (AT) before ICD implantation (n = 38). Implantable
      cardioverter/defibrillator therapies for AT/AF were activated and de-activated
      every 3 months in a cross-over study design. The mean follow-up was 18.5 +/- 7.7
      months (6.29 +/- 2.2 cross-over/patient). Overall, there were 684 episodes of
      ventricular tachyarrhythmias in 48.4% of patients (n = 59). In 33.6% of patients
      (n = 41), 532 supraventricular tachyarrhythmias occurred. Activation of ICD
      therapies for AT/AF did not result in a reduction of ventricular tachyarrhythmias
      (P = 0.92). Patients with monomorphic ventricular tachycardias (mVTs) as index
      arrhythmia for ICD implantation or inducible mVTs in the electrophysiological
      study had the highest probability of recurrences of ventricular tachyarrhythmias.
      CONCLUSION: For patients with standard indications for ICD therapy and no
      indication for cardiac pacing, a dual-chamber ICD capable of atrial
      tachyarrhythmia treatment offers no benefit concerning a reduction of ventricular
      tachyarrhythmias.

PMID- 17440006
TI  - Efficacy of various intravenous immunoglobulin therapy protocols in autoimmune
      and chronic inflammatory disorders.
AB  - OBJECTIVE: To determine the efficacy of various intravenous immunoglobulin (IVIG)
      protocols used in the treatment of autoimmune and chronic inflammatory disorders.
      DATA SOURCES: Literature retrieval was accessed through MEDLINE (November 1984
      March 2007) and a search was conducted using the term intravenous immunoglobulin.
      References cited in the selected articles were also reviewed. STUDY SELECTION AND
      DATA EXTRACTION: Inclusion criteria for studies were (1) English language, (2)
      randomized controlled trials, (3) defined protocols, (4) a minimum of 15
      patients, and (5) objective criteria provided to assess clinical outcomes and
      course. DATA SYNTHESIS: The therapeutic efficacy of IVIG therapy is well
      established, and defined protocols exist for treatment of Kawasaki disease,
      immune thrombocytopenic purpura, Guillain-Barre syndrome, chronic inflammatory
      demyelinating polyneuropathy, multifocal motor neuropathy, and autoimmune
      mucocutaneous blistering diseases. In the absence of a defined protocol, studies
      have demonstrated that IVIG therapy is effective in the treatment of myasthenia
      gravis, dermatomyositis, stiff person syndrome, antineutrophil cytoplasmic
      antibody positive systemic vasculitides, Graves' ophthalmopathy, and certain
      forms of systemic lupus erythematosus. It might also be of benefit in some
      patients with relapsing-remitting multiple sclerosis. The outcomes are variable
      in these studies. In toxic epidermal necrolysis and Stevens-Johnson syndrome, use
      of IVIG has dramatically influenced clinical response and reduced mortality.
      CONCLUSIONS: The cumulative evidence suggests that the clinical outcomes observed
      are significantly influenced by the use of a defined protocol. There is a need
      for multicenter trials approved by the Food and Drug Administration to better
      define the role of IVIG in many disease states. Such studies would be able to
      establish the indications for use, optimal dose, frequency of infusions, duration
      of therapy, and need for gradual withdrawal versus sudden cessation. Defined
      protocols resulting from the study of a large cohort of patients often convince
      insurance companies to create policies that provide access to IVIG therapy.

PMID- 17440007
TI  - Poor preservation efficacy versus quality and safety of pediatric extemporaneous
      liquids.
AB  - BACKGROUND: Most medicines are available only as solid, adult-strength dosage
      forms from which oral extemporaneous liquids are often prepared for children.
      There are few comprehensive reference lists for the preparation of pediatric
      extemporaneous formulations. Some pediatric reformulations are made by diluting
      the suspending vehicle, and a shelf life of up to 3 months can be used without
      documented microbial stability. Although most commercially available ready-to-use
      vehicles are supplied as preserved formulations, it is still common practice in
      many European dispensaries to prepare and dilute these vehicles as required for
      specific prescriptions. OBJECTIVE: To determine what influence dilution of
      vehicles has on the preservation efficiency of extemporaneous formulations.
      METHODS: Suspending vehicles were made by diluting methylcellulose 1% and simple
      syrup, BP (British Pharmacopoeia) in ratios of 1:1 and 1:4. The efficacy of
      antimicrobial preservation was tested according to the 2007 standards required by
      the BP. RESULTS: Dilution in ratios greater than 1:1 failed the BP 2007 criteria.
      Such dilution represents a potential biohazard, especially to premature, newborn,
      or immunocompromised children, exposing them not only to possible organoleptic
      changes of the preparation, but also to ingestion of either dangerous numbers of
      microorganisms or medicines that may have undergone biotransformation, rendering
      them inactive or toxic. CONCLUSIONS: Significant concerns have been raised
      regarding the quality of extemporaneous preparations. We call for further
      research in this neglected area to address issues of antimicrobial preservation,
      including revision of existing quality assurance monographs. Moreover, these
      monographs should take into account testing that simulates multiple dosing from a
      single storage container during the intended in-use shelf life of multidose
      extemporaneous preparations.

PMID- 17440008
TI  - Impact of a pharmacy resident on hospital length of stay and drug-related costs.
AB  - BACKGROUND: The impact of pharmacy residents' interventions on medical rounds has
      not been well evaluated. OBJECTIVE: To assess the impact of a resident's
      interventions on hospital length of stay, describe the types of interventions,
      and assess drug-related cost savings. METHODS: Using a matched control design, we
      conducted an evaluative study of adults admitted to a general internal medicine
      unit over one month. The study group consisted of patients admitted to the
      service of a medical team that included a pharmacy resident and medical
      residents. The pharmacy resident prospectively collected data on patient
      demographics and interventions made during patient admission and follow-up
      rounds. The control group consisted of patients admitted to the service of a team
      consisting of medical residents only, over the same period. The medical records
      of the control group were retrospectively evaluated for potential interventions.
      RESULTS: Forty patients were enrolled in each group (aged 63 +/- 17 y, mean +/-
      SD). In the study group, 250 of 271 interventions were accepted and fulfilled. In
      the control group, 321 potential interventions were identified. The mean length
      of stay of the study group was significantly lower than that of the control group
      (7.9 +/- 7.2 days vs 10.9 +/- 7.9 days, respectively; p = 0.008). In the study
      group and the control group, the total interventions were related to prescribing
      errors (51.3% vs 45.4%), preventable adverse drug events (32.9% vs 42.3%),
      patient monitoring (14% vs 7%), and drug interactions (1.8% vs 5.3%). In the
      study group, the net drug-related cost savings totaled $2087. CONCLUSIONS: Our
      study demonstrates the positive impact of a pharmacy resident on reducing the
      hospital length of stay and producing drug-related cost savings. Most
      interventions prevented adverse drug events and prescribing errors.

PMID- 17440009
TI  - Argatroban anticoagulation in critically ill patients.
AB  - BACKGROUND: Despite long-term use of argatroban in clinical practice, no dosing
      recommendations exist for critically ill patients with multiple organ dysfunction
      (MODS) and suspected or proven heparin-induced thrombocytopenia (HIT). OBJECTIVE:
      To determine the suitability of argatroban use in critically ill patients with
      MODS and HIT. METHODS: We conducted prospective observation of 24 consecutive
      patients with suspected HIT who were being anticoagulated with argatroban (target
      activated partial thromboplastin time [aPTT] 1.5-2 times normal or 50-60 sec)
      using 2 microg/kg/min in the first 5 patients and 0.2 microg/kg/min in the
      subsequent 19 patients. RESULTS: Infusion of argatroban 2 microg/kg/min over 4
      hours caused bleeding complications in 3 patients as aPTT increased from 51 +/-
      18 to 86 +/- 34 seconds (p = 0.02), prothrombin time (PT) decreased from 76 +/-
      27% to 33 +/- 12% of normal reference values, and international normalized ratio
      (INR) increased from 1.4 +/- 0.4 to 2.5 +/- 0.9 (p = 0.007). Infusion of
      argatroban 0.2 microg/kg/min over 4 hours provided sufficient anticoagulation
      without bleeding complications. The aPTT in this population increased from 44 +/-
      9 to 59 +/- 13 seconds (p < 0.001), and PT and INR remained unchanged (76 +/- 22%
      and 69 +/- 23% of normal reference values, 1.3 +/- 0.3 and after 1.3 +/- 0.3,
      respectively [p = 0.4]). Coagulation variables (aPTT, PT, INR) were significantly
      different between both dosing regimens after 4 hours of infusion (p = 0.042 and p
      = 0.003, respectively). The maintenance dose for target aPTT averaged 0.22 +/-
      0.15 microg/kg/min in both groups. CONCLUSIONS: In critically ill patients with
      MODS, argatroban 2 microg/kg/min, as recommended by the manufacturer, resulted in
      extensive anticoagulation. A tenfold lower starting dose is sufficient and safe
      for effective anticoagulation in this specific patient population.

PMID- 17440010
TI  - Transcriptional profiling of testosterone-regulated genes in the skeletal muscle
      of human immunodeficiency virus-infected men experiencing weight loss.
AB  - CONTEXT: HIV-associated wasting and weight loss remain clinically significant
      concerns even in the era of potent antiretroviral therapy. Although androgen
      treatment increases muscle mass, the cell-intrinsic mechanisms engaged remain
      poorly understood. OBJECTIVE: This study was an unbiased approach to identify
      expression profiles associated with testosterone treatment using genome-wide
      microarray analysis of skeletal muscle biopsies. DESIGN, SETTING, AND
      PARTICIPANTS: Forty-four HIV-positive men with weight loss were randomized to
      receive either 300 mg testosterone enanthate or placebo injections im weekly for
      16 wk. Muscle biopsies were obtained at baseline and on treatment d 14. A subset
      of specimens was chosen for microarray analysis, with changes in selected genes
      confirmed by real-time PCR, Western blot analysis, and in vitro culture of muscle
      precursor cells. RESULTS: Significantly greater gains in body mass (+2.05 and 
      1.07 kg, respectively; P = 0.003) and lean body mass by dual-energy x-ray
      absorptiometry (2.93 vs. 0.35 kg, respectively; P = 0.003) were observed in
      subjects treated with testosterone compared with placebo. Microarray analysis
      revealed up-regulation in genes involved in myogenesis and muscle protein
      synthesis, immune regulation, metabolic pathways, and chromatin remodeling.
      Representative genes were confirmed by real-time PCR and protein expression
      studies. In an independent analysis, gene networks that differentiate healthy
      young men from older men with sarcopenia had substantial overlap with those
      activated by testosterone treatment. CONCLUSIONS: These data provide new insights
      into the mechanisms of androgen action and have implications for both development
      of muscle biomarkers and anabolic therapies for wasting and sarcopenia.

PMID- 17440011
TI  - Exonic duplication of the hepatocyte nuclear factor-1beta gene (transcription
      factor 2, hepatic) as a cause of maturity onset diabetes of the young type 5.
AB  - CONTEXT: Maturity onset diabetes of the young (MODY) type 5 has been described as
      the association of early-onset diabetes and renal disease. Actually, MODY5
      encompasses multiple phenotypes, including nondiabetic progressive renal failure,
      kidney and genital tract malformations, atypical familial hyperuricemic
      nephropathy, pancreas atrophy, and liver test abnormalities. The occurrence of
      MODY5 has been associated with various molecular abnormalities of TCF2, including
      missense, nonsense, small insertion/deletions, and splice site mutations, as well
      as large genomic deletions or single exonic deletion of TCF2. DESIGN: Using
      quantitative multiplex PCR amplification of short fluorescent fragments, we have
      analyzed the TCF2 gene in a French family of which three relatives presented a
      MODY5 phenotype. The proband had an extended clinical phenotype, including
      hyperuricemic nephropathy and early gout, chronic renal failure, renal
      morphological abnormalities, abnormal liver tests, and diabetes. His son had
      almost no clinical expression of the disease, whereas his grandson had a
      restricted but severe renal phenotype present from birth. RESULTS: We show that a
      duplication of the exon 5 of TCF2 is responsible for the MODY5 phenotypes in this
      family. CONCLUSIONS: Thus, we describe a novel molecular mechanism that may be
      responsible for MODY5, and we emphasize the wide intrafamilial variability of
      MODY5 expressivity. These observations suggest that the diagnosis of MODY5 may be
      raised even in subjects with partial phenotypes. They also confirm that
      quantitative multiplex PCR amplification of short fluorescent fragments analysis
      should be the first step of genetic screening in patients with a MODY5 phenotype.

PMID- 17440012
TI  - Epistatic effect of cholesteryl ester transfer protein and hepatic lipase on
      serum high-density lipoprotein cholesterol levels.
AB  - OBJECTIVES: Polymorphisms in the hepatic lipase (LIPC -514C > T) and cholesteryl
      ester transfer protein (CETP I405V) genes affect high-density lipoprotein
      cholesterol (HDL-c) levels, but their relationship with cardiovascular disease
      and their combined effect is unclear. The objectives of the current study were to
      characterize the effect of the hepatic lipase variant, and its interaction with
      the CETP variant, in terms of cholesterol levels, atherosclerosis, and risk of
      myocardial infarction (MI). DESIGN: The study was conducted in the Rotterdam
      Study, a large single-center prospective cohort study in people aged 55 yr and
      older. Lipid levels were analyzed using linear regression models, and risk of MI
      was assessed with Cox proportional hazards models. RESULTS: The hepatic lipase
      variant was associated with an increase in serum HDL-c levels of 0.11 mmol/liter
      in both genders, whereas an increased risk of MI was observed only in men [hazard
      ratio, 1.32 (95% confidence interval, 1.05-1.66) for CT vs. CC and 1.75 (95%
      confidence interval, 1.39-2.20) for TT vs. CC]. This effect was independent of
      serum HDL-c. LIPC -514C > T interacted with CETP I405V with respect to serum HDL
      c concentrations. Those homozygous for both mutations saw a marked elevation in
      HDL-c levels (0.29 mmol/liter, P(interaction) = 0.05). These increased HDL-c
      levels, however, were not inversely associated with atherosclerosis or MI risk.
      CONCLUSIONS: LIPC genotype affects HDL-c levels and risk of MI in males. The
      interaction of this variant with CETP on HDL-c levels helps elucidate the
      underlying mechanisms and suggests that the beneficial effects of CETP inhibition
      may vary in particular subgroups.

PMID- 17440013
TI  - Clinical review: Thyroid dysfunction and effects on coagulation and fibrinolysis:
      a systematic review.
AB  - CONTEXT: Various changes in the coagulation-fibrinolytic system have been
      described in patients with an excess or deficiency of thyroid hormones. The
      purpose of this systematic review is to summarize the effects of hyperthyroidism
      and hypothyroidism on these systems. EVIDENCE ACQUISITION: All published case
      control or interventional cohort studies that evaluated the effects of
      hyperthyroidism and hypothyroidism on the coagulation-fibrinolytic system in vivo
      were identified by a computer-assisted search of the MEDLINE and EMBASE
      electronic databases. A scoring system was used to divide studies into three
      quality categories: high, medium, and low quality. EVIDENCE SYNTHESIS: A total of
      36 papers were included. Because in several papers more than one case-control
      study or both a case-control and intervention study were described, a total of 39
      case-control studies and 24 interventional cohort studies were analyzed. No high
      quality study was identified. Three (7.7%) case-control and eight (33.3%) cohort
      studies were of medium quality. A total of 19 tests were investigated in the
      medium-quality studies. These tests revealed a hypocoagulable state for overt
      hypothyroidism and a hypercoagulable state for overt hyperthyroidism.
      CONCLUSIONS: This analysis confirmed that clinically overt hyperthyroidism and
      hypothyroidism modify the coagulation-fibrinolytic balance, indicating that
      thyroid hormone excess or deficit is the probable main pathophysiological
      mechanism. Patients with overt hypothyroidism and overt hyperthyroidism appear to
      have an increased risk of bleeding and of thrombosis, respectively.

PMID- 17440014
TI  - Peptide products of the neurotrophin-inducible gene vgf are produced in human
      neuroendocrine cells from early development and increase in hyperplasia and
      neoplasia.
AB  - BACKGROUND: Although the neurotrophin-inducible gene vgf is expressed in
      mammalian neurons and endocrine cells, limited data is available in man. AIM: The
      objective of the study was to map proVGF peptides in human endocrine cells during
      development, adulthood, hyperplasia, and tumors. METHODS: Antisera were generated
      against peptides related to internal cleavage or cleavage-amidation sites (rat
      proVGF(422-430) and human proVGF(298-306)-NH2) and the proVGF C-terminal ending
      (human proVGF(607-615)). Developing and normal adult endocrine cells,
      hyperplastic endocrine lesions (thyroid, parathyroid, lung, and stomach), and 120
      tumors (102 endocrine) were studied. Immunogold electron microscopy was performed
      on normal adult pancreas and gut, and Western blotting was performed on extracts
      of control tissues and endocrine tumors. RESULTS: proVGF fragments were revealed
      in developing pituitary, gut, pancreas, and adrenal medulla from 10 gestational
      weeks, in normal adult pituitary and adrenal medulla, pancreatic glucagon, and
      insulin cells and gut serotonin cells, in hyperplastic thyroid calcitonin cells,
      lung P cells, gastric enterochromaffin-like cells, and gastrin cells, and in 88
      of 102 endocrine tumors. At electron microscopy proVGF immunoreactivity was
      restricted to electron-dense granules. Western blotting revealed large molecular
      weight forms and cleavage fragments in both control tissues and tumor extracts.
      CONCLUSIONS: proVGF-related peptides are present in endocrine cells early during
      development and adulthood and increase in hyperplasia and tumors, and proVGF
      fragments could be novel diagnostic tools for endocrine cells and related
      lesions, including tumors.

PMID- 17440015
TI  - Bexarotene-induced hypothyroidism: bexarotene stimulates the peripheral
      metabolism of thyroid hormones.
AB  - OBJECTIVE: Therapy with the retinoid X receptor agonist bexarotene is associated
      with hypothyroidism caused by decreased pituitary TSH secretion. To evaluate the
      effects of bexarotene on peripheral thyroid hormone metabolism, we performed a
      study in athyreotic subjects on a fixed substitution dose with L-T4. DESIGN: The
      design was an open prospective 6-wk intervention study. METHODS: Ten athyreotic
      patients with pulmonary metastases of differentiated thyroid carcinoma received 6
      wk redifferentiation treatment with 300 mg bexarotene/d. L-T4 doses were kept
      stable. Before and in the sixth week of therapy, serum levels of total T4, free
      T4 (FT4), T3, reverse T3 (rT3), and TSH were measured. To study nondeiodinase
      mediated thyroid hormone degradation, serum levels of T4 sulfate (T4S) were
      measured. Recombinant human TSH was administered before and in the sixth week of
      bexarotene therapy. RESULTS: Bexarotene induced profound decreases in total T4
      (56% of baseline), FT4 (47%), T3 (69%), rT3 (51%), and T4S (70%) in all patients,
      whereas TSH levels were not affected. The T3/rT3 ratio increased by 43%, and the
      T4S/FT4 ratio increased by 48%. Serum TSH levels before and after recombinant
      human TSH were unaffected by bexarotene. CONCLUSIONS: In the present study, we
      demonstrate that increased peripheral degradation of thyroid hormones by a
      nondeiodinase-mediated pathway contributes to bexarotene induced-hypothyroidism.

PMID- 17440016
TI  - Etiology of early-onset type 2 diabetes in Indians: islet autoimmunity and
      mutations in hepatocyte nuclear factor 1alpha and mitochondrial gene.
AB  - CONTEXT: Indians are at high risk of developing type 2 diabetes mellitus (T2DM)
      at an early age, despite their lower body mass index. Studies on the etiology of
      patients presenting as early-onset T2DM in this racial group are not available.
      OBJECTIVE: The objective was to delineate the clinical features in young Indian
      patients with T2DM and to determine the role of mutations in the hepatocyte
      nuclear factor 1alpha (HNF1alpha) gene [MODY3 (maturity-onset diabetes of the
      young, type 3)], mitochondrial A3243G mutation, and islet autoimmunity in its
      etiology. DESIGN: This was an observational cohort study. SETTING: The setting
      was an outpatient diabetes clinic in a teaching hospital. PATIENTS: Ninety-six
      consecutive young patients with T2DM (onset, <or=30 yr) were included in the
      study. INTERVENTIONS: Glutamic acid decarboxylase and insulinoma antigen 2
      antibodies, mitochondrial A3243G mutation, and the common HNF1alpha mutation
      P291fsinsC were measured in all patients. The entire HNF1alpha gene was studied
      for mutations in 32 subjects with onset less than 25 yr or with normal weight.
      The common HNF1alpha A98V polymorphism was studied in 91 patients. RESULTS: The
      patients were clinically heterogeneous, with 42% having a normal body mass index.
      Glutamic acid decarboxylase antibodies were present in three (3%) subjects and
      mitochondrial A3243G mutation in one (1%) subject. The P291fsinsC mutation was
      not detected in any patient. A MODY3 mutation (R200W) was detected in one patient
      (3%). In this family, diabetes cosegregated with the R200W mutation in the
      proband and his youngest brother but not in three paternal uncles. The Val 98
      allele was associated with T2DM (allele frequency, 0.14 vs. 0.03 in controls;
      odds ratio, 5.2; P < 0.001). CONCLUSIONS: Despite a significant proportion of
      young Indian patients with T2DM having normal weight, islet autoimmunity, A3243G
      mitochondrial, and HNF1alpha gene mutations were infrequent.

PMID- 17440017
TI  - Alcohol consumption and lipoprotein subclasses in older adults.
AB  - CONTEXT: Limited evidence suggests that alcohol intake may be associated with
      lipoprotein subclass distribution, which could mediate its relationship with
      coronary heart disease. OBJECTIVES: The objective was to determine the
      relationship of alcohol intake with lipoprotein particle subclasses. DESIGN,
      SETTING, AND PARTICIPANTS: The study included a cross-sectional analysis of 1850
      participants of the Cardiovascular Health Study aged 65 yr and older and free of
      clinical cardiovascular disease. MAIN OUTCOME MEASURE: Lipoprotein subclass
      distribution was measured with nuclear magnetic resonance spectroscopy, according
      to self-reported alcohol intake. RESULTS: Alcohol intake was associated with
      total low-density lipoprotein (LDL) particles in a U-shaped manner. Consumers of
      one or more drinks per week had the highest number of large LDL particles,
      whereas consumers of 7-13 drinks per week had the lowest number of small LDL
      particles. Alcohol intake was strongly positively associated with large- and
      medium-sized high-density lipoprotein (HDL) particles but had an inverse
      relationship with concentrations of small HDL particles and small- and medium
      sized very-low-density lipoprotein particles. Average particle sizes of all three
      lipoproteins were positively associated with alcohol intake. Associations were
      generally stronger among women than men but in similar directions. Beverage type
      did not consistently modify these findings. CONCLUSIONS: Alcohol intake is
      associated with less total LDL particles, lower levels of small LDL, HDL, and
      very-low-density lipoprotein particles, and higher levels of large LDL and medium
      and large-sized HDL particles in older adults free of prevalent clinical
      cardiovascular disease.

PMID- 17440018
TI  - Activating transcription factor 6 polymorphisms and haplotypes are associated
      with impaired glucose homeostasis and type 2 diabetes in Dutch Caucasians.
AB  - CONTEXT: Activating transcription factor 6 (ATF6) is critical for initiation and
      full activation of the unfolded protein response. An association between genetic
      variation in ATF6 and type 2 diabetes (DM2) was recently reported in Pima
      Indians. OBJECTIVES: To investigate the broader significance of this association
      for DM2, replication studies in distinct ethic populations are required. We
      investigated ATF6 for its association with DM2 in Dutch Caucasians.
      DESIGN/SETTING: A genetic association study was conducted at an academic research
      laboratory. STUDY PARTICIPANTS: Two independent Dutch cohorts were studied.
      Cohort 1 (n = 154) was used to evaluate genetic variation in the ATF6 gene in
      relation to glucose homeostasis in the general population. Cohort 2 (n = 798)
      consisted of patients with DM2, impaired glucose tolerance, impaired fasting
      glucose, and normoglycemic control subjects, and was used to investigate ATF6
      polymorphisms for their contribution to disturbed glucose homeostasis and DM2.
      MAIN OUTCOME MEASURES: There were 16 tag single nucleotide polymorphisms
      genotyped in all subjects of both cohorts. Those single nucleotide polymorphisms
      included three nonsynonymous coding variants and captured all common allelic
      variation of ATF6. RESULTS: Our data show that common ATF6 variants are
      associated with elevated glucose levels in the general population (cohort 1, P =
      0.005-0.05). Furthermore, the majority of these variants, and haplotypes thereof,
      were significantly associated with impaired fasting glucose, impaired glucose
      tolerance, and DM2 (cohort 2, P = 0.006-0.05). Associated variants differ from
      those identified in Pima Indians. CONCLUSIONS: Our results strengthen the
      evidence that one or more variants in ATF6 are associated with disturbed glucose
      homeostasis and DM2.

PMID- 17440019
TI  - Pulsatile luteinizing hormone amplitude and progesterone metabolite excretion are
      reduced in obese women.
AB  - CONTEXT: Female obesity is linked to abnormal menstrual cycles, infertility,
      reproductive wastage, and deficient LH, FSH, and progesterone secretion.
      OBJECTIVE AND DESIGN: To elucidate the reproductive defects associated with
      obesity, we sampled 18 eumenorrheic (nonpolycystic ovary syndrome) women with a
      mean +/- sem body mass index of 48.6 +/- 1.4 kg/m2 with daily, first morning
      voided urine collections, seven of whom also had early follicular phase 12-h,
      every 10-min blood sampling to assess LH pulses. Daily hormones were compared
      with 11 eumenorrheic, normal-weight controls. A separate control group of 12
      eumenorrheic, normal-weight women was used for the LH pulse studies. MAIN OUTCOME
      MEASURES: Assays for LH (serum and urine) and FSH, and estradiol and progesterone
      metabolites (estrone conjugate and pregnanediol glucuronide; urine) were
      performed. Daily hormones were meaned and normalized to a 28-d cycle length. LH
      pulsations were determined using two objective methods. Group means were compared
      using t tests. RESULTS: Reduced whole-cycle mean, normalized pregnanediol
      glucuronide was observed in obese (38.2 +/- 2.1 microg/mg creatine) compared with
      normal-weight women (181.3 +/- 35.1 microg/mg creatine; P = 0.002), without
      significant differences in LH, FSH, or estrone conjugate. Early follicular phase
      LH pulse frequency did not differ from normal-weight women, but both amplitude
      and mean LH were dramatically reduced in obese women (0.8 +/- 0.1 and 2.0 +/- 0.3
      IU/liter) compared with controls (1.6 +/- 0.2 and 3.4 +/- 0.2 IU/liter; P <
      0.01). CONCLUSIONS: A novel defect in the amplitude but not the frequency of LH
      pulsations appears to underlie the reproductive phenotype of obesity. The deficit
      in pregnanediol glucuronide appears to exceed the deficit in LH. The patterns of
      hypothalamic-pituitary-ovarian axis function unique to the obese state differ
      from other abnormal reproductive states.

PMID- 17440020
TI  - Addition of monofluorophosphate to estrogen therapy in postmenopausal
      osteoporosis: a randomized controlled trial.
AB  - INTRODUCTION: Treatment of osteoporosis with high-dose fluoride alone does not
      reduce fracture risk. We hypothesized that the antifracture efficacy of fluoride
      could be optimized by its use in low doses combined with an antiresorptive agent.
      EXPERIMENTAL SUBJECTS: Subjects included 80 women with postmenopausal
      osteoporosis who had been taking estrogen for at least 1 yr. METHODS: Subjects
      were randomized to receive monofluorophosphate (MFP) (fluoride content of 20
      mg/d) or placebo over 4 yr in a double-blind trial. RESULTS AND DISCUSSION: There
      were progressive increases in lumbar spine bone density over the duration of the
      study (MFP, 22%; placebo, 6%; P < 0.0001). In the trabecular bone of L3, these
      increases were even greater (MFP, 49%; placebo, 2.5%; P < 0.0001). In the
      proximal femur, there were smaller but significant treatment effects (P = 0.015).
      Total body scans and their subregions also showed significantly greater increases
      in the MFP group. Bone formation markers increased significantly in the MFP group
      at yr 1. Hyperosteoidosis was present in biopsies from five of seven MFP
      subjects, with osteomalacia in two of seven. The hazards ratio for vertebral
      fractures was 0.20 (95% confidence interval, 0.05-1.30), and the incidence rate
      ratio was 0.12 (95% confidence interval, 0.06-0.23; P < 0.01). The hazards ratio
      for nonvertebral fractures was 3.3 (95% confidence interval, 0.8-12.0).
      CONCLUSIONS: We conclude that fluoride at 20 mg/d produces substantial increases
      in bone mineral density but still interferes with bone mineralization. This
      indicates that most previous studies with this ion have used toxic doses and that
      much lower doses should be assessed to find a safe dose window for the use of
      this powerful anabolic agent.

PMID- 17440021
TI  - Retinol binding protein-4 levels and clinical features of type 2 diabetes
      patients.
AB  - CONTEXT: Retinol binding protein (RBP)-4 is a recently identified adipocytokine
      that is associated with insulin resistance. OBJECTIVES: The aim was to
      investigate the association between RBP4 and various markers related to insulin
      resistance and diabetic complications in type 2 diabetic patients. The effect on
      RBP4 of the addition of pioglitazone to other diabetic medications was also
      examined. DESIGN, SETTING, PATIENTS, INTERVENTION, AND MAIN OUTCOME MEASURES:
      RBP4 levels were measured in 101 hospitalized patients with type 2 diabetes and
      in 22 nonhospitalized control subjects. Endothelial function was evaluated using
      flow-mediated vasodilatation. In a further 22 nonhospitalized type 2 diabetic
      patients, pioglitazone (30 mg/d) was administered for 12 wk while other
      medications for diabetes were continued. RESULTS: There was a significant
      elevation of RBP4 levels in diabetic patients compared with healthy subjects.
      RBP4 showed significant positive correlations with triglyceride, systolic blood
      pressure, and log urinary albumin excretion, and significant negative
      correlations with high-density lipoprotein cholesterol and flow-mediated
      vasodilatation. In stepwise regression analysis, log urinary albumin excretion,
      triglyceride, and gender showed a significant association with RBP4. RBP4 was
      significantly elevated in patients with proliferative-diabetic retinopathy
      compared with nondiabetic retinopathy and simple-diabetic retinopathy patients.
      The addition of pioglitazone for 12 wk to other diabetic medications the patients
      were already taking did not affect the serum RBP4 concentration. CONCLUSIONS: The
      current study shows that RBP4 is associated with variables related to insulin
      resistance and diabetic complications. The addition of pioglitazone for 12 wk to
      other diabetic medications the patients were already taking did not affect serum
      RBP4 levels.

PMID- 17440022
TI  - Globalized migration and transnational epidemiology.

PMID- 17440023
TI  - Decreased risk of death from coronary heart disease amongst men with higher
      'femininity' scores: a general population cohort study.
AB  - CONTEXT: At all ages men have higher rates of coronary heart disease (CHD) than
      women, although similar proportions of men and women eventually die of CHD.
      Gender differences in CHD incidence and mortality are often explained in relation
      to biological (hormonal) and behavioural risk factors (e.g. smoking), but
      psychological factors and broader social constructions of gender are rarely
      considered. OBJECTIVE: To examine the relationship between measures of gender
      role orientation at baseline in 1988 and mortality from CHD over 17 years (to
      June 2005). DESIGN: Prospective cohort study linked to national mortality
      reporting. SETTING: Socially varied, mainly urban area centred on city of Glasgow
      in West Central Scotland, UK. PARTICIPANTS: In total, 1551 participants (704 men
      and 847 women) aged 55 years took part in detailed interviews with nurses trained
      in survey methods in 1988. These included a wide range of measures of physical
      development and functioning, self reported health and health behaviour, personal
      and social circumstances and a measure of gender role orientation (yielding
      scores for 'masculinity' and 'femininity'). MAIN OUTCOME MEASURES: Mortality from
      CHD up to June 2005 (88 CHD deaths in men; 41 CHD deaths in women). RESULTS:
      After adjusting for smoking, binge drinking, body mass index, systolic blood
      pressure, household income and psychological well-being, higher 'femininity'
      scores in men were associated with a lower risk of CHD death (hazards ratio per
      unit increase in 'femininity' score 0.65, 95% CIs 0.48-0.87, P = 0.004). No such
      relationship was observed amongst women. 'Masculinity' scores were unrelated to
      CHD mortality in either men or women. CONCLUSIONS: These results suggest that
      social constructions of gender influence the risk of ill health, here death from
      CHD. Men who are less able to identify themselves with characteristics identified
      as 'feminine' or expressive (who have a more limited stereotypically masculine
      self-image) may be at increased risk of coronary disease. Further research on the
      link between social constructions of gender and health is needed.

PMID- 17440024
TI  - Blinded trials taken to the test: an analysis of randomized clinical trials that
      report tests for the success of blinding.
AB  - BACKGROUND: Blinding can reduce bias in randomized clinical trials, but blinding
      procedures may be unsuccessful. Our aim was to assess how often randomized
      clinical trials test the success of blinding, the methods involved and how often
      blinding is reported as being successful. METHODS: We analysed a random sample of
      blinded randomized clinical trials indexed in the The Cochrane Central Register
      of Controlled Trials and published in 2001. We identified 1599 blinded trials,
      and noted if they had conducted any test for the success of blinding. We also
      selected 200 trials randomly that did not report any such test, and sent a
      questionnaire to the corresponding authors asking them if they had conducted any
      tests. RESULTS: Thirty-one out of 1599 trials (2%) reported tests for the success
      of blinding. Test methods varied, and reporting was generally incomplete.
      Blinding was considered successful in 14 out of the 31 trials (45%) and unclear
      in 10 (32%). Of the seven trials (23%) reporting unsuccessful blinding the risk
      of a biased trial result was either not addressed or was discounted in six cases.
      We received 130 questionnaires from trial authors (65%) of which 15 (12%)
      informed that they had conducted, but not published, tests. CONCLUSIONS: Blinding
      is rarely tested. Test methods vary, and the reporting of tests, and test
      results, is incomplete. There is a considerable methodological uncertainty how
      best to assess blinding, and an urgent need for improved methodology and improved
      reporting.

PMID- 17440025
TI  - Estimating the number of vertically HIV-infected children eligible for
      antiretroviral treatment in resource-limited settings.
AB  - BACKGROUND: With the gradual roll-out of antiretroviral therapy (ART) to delay
      progression of HIV disease in children in programmes across sub-Saharan Africa
      and resource-limited settings elsewhere, reliable information on the number of
      vertically infected children eligible for such treatment is urgently required.
      METHODS: We present a model to estimate the number of vertically HIV-infected
      children by age who have progressed to moderate to severe disease (MSD) and as
      such are eligible for ART on the basis of clinical disease, allowing for:
      antenatal HIV prevalence, use of interventions to prevent mother-to-child
      transmission (PMTCT), infant feeding policies and availability of co-trimoxazole
      to prevent opportunistic infections that may hasten the onset of serious disease.
      The model assumptions were informed by published evidence and expert opinion;
      rates of progression to serious disease were inferred from mortality of infected
      and uninfected children of HIV-infected mothers; and mortality among children
      treated with ART was based on a study of treated children in Abidjan. To allow
      widespread use the model has been developed using the Excel spreadsheet software.
      RESULTS: With South Africa as a hypothetical example, published antenatal
      prevalence and demographic data, and assuming PMTCT coverage with single dose
      nevirapine of 11%, all exposed and infected children receive co-trimoxazole, and
      various infant feeding policy scenarios, estimated numbers of children eligible
      for ART are presented. CONCLUSIONS: This model is easy to implement and flexible
      and can be used in ART programmes at national and local level.

PMID- 17440028
TI  - Are childhood socio-economic circumstances related to coronary heart disease
      risk? Findings from a population-based study of older men.
AB  - BACKGROUND: The independent influence of childhood social circumstances on health
      in later life remains uncertain. We examined the extent to which childhood socio
      economic circumstances are related to the risk of coronary heart disease (CHD) in
      older British men, taking account of adult social class and behavioural risk
      factors. METHODS: A socio-economically representative sample of 5552 British men
      (52-74 years) with retrospective assessment of childhood socio-economic
      circumstances (father's occupation and childhood household amenities) who were
      followed up for CHD (fatal and non-fatal) for 12 years. RESULTS: Men whose
      childhood social class was manual had an increased hazard ratio (HR) 1.34 (95% CI
      1.11-1.63)-this effect was diminished when adjusted for adult social class and
      adult behavioural risk factors (cigarette smoking, alcohol, physical activity and
      body weight) (HR 1.19; 95% CI 0.97-1.46). Men whose family did not own a car in
      their childhood were at increased CHD risk even after adjustments for adult
      social class and behaviours (HR 1.35, 95% CI 1.04-1.75). Men with combined
      exposure to both childhood and adult manual social class had the highest risk of
      CHD (HR 1.51; 95% CI 1.19-1.91); this was substantially reduced by adjustment for
      adult behavioural risk factors (adjusted HR 1.28; 95% CI 0.99-1.65). CONCLUSIONS:
      Less affluent socio-economic conditions in childhood may have a modest persisting
      influence on risk of CHD in later life.

PMID- 17440029
TI  - Commentary: on the incidence of histological prostate cancer and the probable
      diagnosis of cases with tumours too small to produce symptoms or to attract
      attention on physical examination--the findings of Dr Arnold Rice Rich.

PMID- 17440031
TI  - Race and risk of schizophrenia in a US birth cohort: another example of health
      disparity?
AB  - BACKGROUND: Immigrant groups in Western Europe have markedly increased rates of
      schizophrenia. The highest rates are found in ethnic groups that are
      predominantly black. Separating minority race/ethnicity from immigration in
      Western Europe is difficult; in the US, these issues can be examined separately.
      Here we compared rates of schizophrenia between whites and African Americans and
      evaluated whether the association was mediated by socioeconomic status (SES) of
      family of origin in a US birth cohort. METHODS: Study subjects were offspring of
      women enrolled during pregnancy at Alameda County Kaiser Permanente Medical Care
      Plan clinics (1959-66) in the Child Health and Development Study. For
      schizophrenia spectrum disorders, 12 094 of the 19 044 live births were followed
      over 1981-97. The analysis is restricted to cohort members whose mothers
      identified as African American or white at intake. Stratified proportional
      hazards regression was the method of analysis; the robustness of findings to
      missing data bias was assessed using multiple imputation. RESULTS: African
      Americans were about 3-fold more likely than whites to be diagnosed with
      schizophrenia [Rate Ratio (RR) = 3.27; 95% confidence interval (CI): 1.71-6.27].
      After adjusting for indicators of family SES at birth, the RR was about 2-fold
      (RR = 1.92; 95% CI: 0.86-4.28). Using multiple imputation in the model including
      family SES indicators, the RR for race and schizophrenia was strengthened in
      comparison with the estimate obtained without imputation. CONCLUSION: The data
      indicate substantially elevated rates of schizophrenia among African Americans in
      comparison with whites in this birth cohort. The association may have been partly
      but not wholly mediated by an effect of race on family SES.

PMID- 17440032
TI  - Effects of passive smoking on heart rate variability, heart rate and blood
      pressure: an observational study.
AB  - BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been shown to
      increase the risk for cardiovascular diseases and death, and autonomic
      dysfunction (specifically, reduced heart rate variability (HRV)) is a predictor
      of increased cardiac risk. This study tests the hypothesis that ETS exposure
      reduces HRV in the general population and discusses possible pathways. METHODS:
      This cross-sectional study was conducted between 2001 and 2003 and is part of the
      SAPALDIA (Swiss Cohort Study on Air Pollution and Lung Diseases in Adults) study.
      The analysis included 1218 randomly selected non-smokers aged 50 and above who
      participated in 24-h electrocardiogram recordings. Other examinations included an
      interview, investigating health status (especially respiratory and cardiovascular
      health and health relevant behaviours and exposure to ETS) and measurements of
      blood pressure, body height and weight. RESULTS: Subjects exposed to ETS at home
      or at work for more than 2 h/day had a difference of -15% in total power (95%CI: 
      26 to -3%), low frequency power (-28 to -1%), low/high frequency ratio (-26 to 
      3%) and -18% (-29 to -4%) in ultralow frequency power of HRV compared with
      subjects not exposed to ETS at home or work. We also found a 2.7% (-0.01 to
      5.34%) higher heart rate during the recording in exposed subjects. CONCLUSIONS:
      Exposure to ETS at home and work is associated with lower HRV and with higher
      heart rate in an ageing population. Our findings suggest that exposure to ETS
      increases cardiac risk through disturbances in the autonomic nervous system.

PMID- 17440033
TI  - Angiotensin II-mediated oxidative stress promotes myocardial tissue remodeling in
      the transgenic (mRen2) 27 Ren2 rat.
AB  - Angiotensin II (ANG II) contributes to cardiac remodeling, hypertrophy, and left
      ventricular dysfunction. ANG II stimulation of the ANG type 1 receptor (AT(1)R)
      generates reactive oxygen species via NADPH oxidase, which facilitates this
      hypertrophy and remodeling. This investigation sought to determine whether
      cardiac oxidative stress and cellular remodeling could be attenuated by in vivo
      AT(1)R blockade (AT(1)B) (valsartan) or superoxide dismutase/catalase mimetic
      (tempol) treatment in a rodent model of chronically elevated tissue levels of ANG
      II, the transgenic (mRen2) 27 rat (Ren2). Ren2 rats overexpress the mouse renin
      transgene with resultant hypertension, insulin resistance, proteinuria, and
      cardiovascular damage. Young (6-7 wk old) male Ren2 and age-matched Sprague
      Dawley rats were treated with valsartan (30 mg/kg), tempol (1 mmol/l), or placebo
      for 3 wk. Heart tissue NADPH oxidase (NOX) activity and immunohistochemical
      analysis of subunits NOX2, Rac1, and p22(phox), heart tissue malondialdehyde, and
      insulin-stimulated protein kinase B (Akt) activation were measured. Structural
      changes were assessed with cine MRI, transmission electron microscopy, and light
      microscopy. Increases in septal wall thickness and altered systolic function
      (cine MRI) were associated with perivascular fibrosis and increased mitochondria
      in Ren2 on light and transmission electron microscopy (P < 0.05). AT(1)B, but not
      tempol, reduced blood pressure (P < 0.05); significant improvements were seen
      with both AT(1)B and tempol on NOX activity, subunit expression, malondialdehyde,
      and insulin-mediated activation/phosphorylation of Akt (each P < 0.05).
      Collectively, these data suggest cardiac oxidative stress-induced structural and
      functional changes are driven, in part, by AT(1)R-mediated increases in NADPH
      oxidase activity.

PMID- 17440034
TI  - Adipose tissue distribution in relation to insulin resistance in type 2 diabetes
      mellitus.
AB  - Insulin resistance (IR) is typically more severe in obese individuals with type 2
      diabetes (T2DM) than in similarly obese non-diabetics but whether there are group
      differences in body composition and whether such differences contribute to the
      more severe IR of T2DM is uncertain. DEXA and regional CT imaging were conducted
      to assess adipose tissue (AT) distribution and fat content in liver and muscle in
      67 participants with T2DM (F39/M28, age 60 +/- 7 yr, BMI 34 +/- 3 kg/m(2)) and in
      35 similarly obese, non-DM volunteers (F20/M15, age 55 +/- 8 yr, BMI 33 +/- 2
      kg/m(2)). A biopsy of subcutaneous abdominal AT was done to measure adipocyte
      size. A glucose clamp was performed at an insulin infusion of 80 mU x min(-1) x
      m(-2). There was more severe IR in T2DM (6.1 +/- 2.3 vs. 9.9 +/- 3.3 mg x min(-1)
      x kg FFM(-1); P < 0.01). Group comparisons of body composition parameters was
      performed after adjusting for the effect of age, gender, race, height and total
      fat mass (FM). T2DM was associated with less leg FM (-1.2 +/- 0.4 kg, P < 0.01),
      more trunk FM (+1.1 +/- 0.4 kg, P < 0.05), greater hepatic fat (P < 0.05), and
      more subfascial adipose tissue around skeletal muscle (P < 0.05). There was a
      significant group x sex interaction for VAT (P < 0.01), with greater VAT in women
      with T2DM (P < 0.01). Mean adipocyte size (AS) did not significantly differ
      across groups, and smaller AS was associated with increased leg FM, whereas
      larger AS was related to more trunk FM (both P < 0.05). Group differences in IR
      were less after adjusting for group differences in leg FM, trunk FM, and hepatic
      fat, but these adjustments only partially accounted for the greater severity of
      IR in T2DM. In summary, T2DM, compared with similarly obese nondiabetic men and
      women, is associated with less leg FM and greater trunk FM and hepatic fat.

PMID- 17440035
TI  - Transcriptional response of human dendritic cells to Borrelia garinii--defective
      CD38 and CCR7 expression detected.
AB  - Lyme borreliosis is a disease, which can affect several organs and cause a
      variety of symptoms. In some patients, the infection may become chronic, even
      after antibiotic therapy, and cause persisting damage. Dendritic cells (DC) are
      involved in the initiation of innate and adaptive immune responses. To study
      interactions between Borrelia garinii (Bg), one of the causative agents of Lyme
      borreliosis, and human DC, we used a cDNA microarray to compare the Bg-induced DC
      transcriptional response with the response induced by LPS. The Bg-induced
      response consisted of a smaller number of genes than the LPS-induced response.
      The microarray showed that the ectoenzyme CD38, which has an important role in DC
      chemotaxis and migration to lymph nodes, was strongly up-regulated by LPS but
      practically not at all by Bg. This finding was confirmed with quantitative RT-PCR
      and with flow cytometry at the protein level. In addition, RT-PCR showed that
      CCR7 expression was 11-fold greater in LPS-stimulated than in Bg-stimulated
      cells. These findings suggest that Bg may affect crucial DC functions by blocking
      the up-regulation of important molecules in DC migration to lymph nodes, thus
      affecting further immune responses in Lyme borreliosis infection.

PMID- 17440036
TI  - Diabetes and risk of breast cancer in Asian-American women.
AB  - The role of diabetes in the etiology of breast cancer in Asian-Americans is not
      known. We investigated the relation between diabetes and breast cancer risk in a
      population-based case-control study in Los Angeles County that included 1248
      Asian-American women with incident, histologically confirmed breast cancer and
      1148 control women, who were frequency matched to cases on age, Asian ethnicity
      and neighborhood of residence. The relation between history of diabetes and serum
      concentrations of estrogens, androgens and sex hormone-binding globulin (SHBG)
      was investigated in 212 post-menopausal control women. A history of diabetes was
      statistically significantly associated with breast cancer risk [odds ratio (OR) =
      1.68, 95% confidence interval = 1.15-2.47] after adjusting for reproductive and
      other factors. This increased risk was unchanged after further adjustment for
      body mass index (BMI) and waist to hip ratio (WHR). We found a stronger diabetes
      breast cancer association in women with lower BMI (< or = 22.7) (adjusted OR =
      3.50, P = 0.011) than those with higher BMI (>22.7) (adjusted OR = 1.39, P =
      0.23) but this difference in ORs was not statistically significant. Our results
      also show that the diabetes-breast cancer association was observed only in
      low/intermediate soy consumers (OR = 2.48, P = 0.0008) but not among high soy
      consumers (OR = 0.75, P = 0.41) (P interaction = 0.014). Controls who were
      diabetic showed significantly lower SHBG (20%) (P = 0.02) but higher free
      testosterone levels (26%) (P = 0.08) than women without such a history after
      adjusting for BMI and WHR. Our results support the hypothesis that diabetes may
      have a role in the development of breast cancer, influencing risk via both sex
      hormone and insulin pathways.

PMID- 17440037
TI  - Pharmacological profile of the thyroid hormone receptor antagonist NH3 in rats.
AB  - NH3 is a thyroid hormone receptor (TR) antagonist that inhibits binding of
      thyroid hormones to their receptor and that inhibits cofactor recruitment. It was
      active in a tadpole tail resorption assay, with partial agonist activity at high
      concentrations. We determined the effect of NH3 on the cholesterol-lowering,
      thyroid stimulating hormone (TSH)-lowering, and tachycardic action of thyroid
      hormone (T(3)) in rats. Cholesterol-fed, euthyroid rats were treated for 7 days
      with NH3, and a dose response (46.2-27,700 nmol/kg/day) was determined. We also
      determined the effect of two doses of T(3) on the NH3 dose-response curve. NH3
      decreased heart rate modestly starting at 46.2 nmol/kg/day, but the effect was
      lost at >2920 nmol/kg/day. At 27,700 nmol/kg/day, tachycardia was seen,
      suggesting partial agonist activity. NH3 increased plasma cholesterol to a
      maximum of 27% at 462 nmol/kg/day. At higher doses, cholesterol was reduced,
      suggesting partial agonist activity. Plasma TSH was increased from 46.2 to 462
      nmol/kg/day NH3, but at higher doses, this effect was lost, and partial agonist
      effects were apparent. T(3) at 15.4 and 46.2 nmol/kg/day increased heart rate,
      reduced cholesterol, and reduced plasma TSH. NH3 inhibited the cholesterol
      lowering, TSH-lowering and tachycardic effects of 15.4 nmol/kg/day T(3), but much
      of the effect was lost at >924 nmol/kg/day doses. NH3 had no effect on the
      cholesterol-lowering action of 46.2 nmol/kg/day T(3), but it inhibited the
      tachycardic and TSH suppressant effects up to the 924 nmol/kg/day dose. Single
      doses of 462 and 27,700 nmol/kg caused no TR inhibitory effects. In conclusion,
      NH3 has TR antagonist properties on T(3)-responsive parameters, but it has
      partial agonist properties at higher doses.

PMID- 17440038
TI  - Understanding hearing through deafness.

PMID- 17440039
TI  - Transgene containment by maternal inheritance: effective or elusive?

PMID- 17440040
TI  - Probing nitrogen metabolism in the redox gradient of the Black Sea.

PMID- 17440041
TI  - The Rac1 guanine nucleotide exchange factor Tiam1 mediates EphB receptor
      dependent dendritic spine development.
AB  - Dendritic spines are small, actin-rich protrusions on the surface of dendrites
      that receive the majority of excitatory synaptic inputs in the brain. The
      formation and remodeling of spines, processes that underlie synaptic development
      and plasticity, are regulated in part by Eph receptor tyrosine kinases. However,
      the mechanism by which Ephs regulate actin cytoskeletal remodeling necessary for
      spine development is not fully understood. Here, we report that the Rac1 guanine
      nucleotide exchange factor Tiam1 interacts with the EphB2 receptor in a kinase
      dependent manner. Activation of EphBs by their ephrinB ligands induces the
      tyrosine phosphorylation and recruitment of Tiam1 to EphB complexes containing
      NMDA-type glutamate receptors. Either knockdown of Tiam1 protein by RNAi or
      inhibition of Tiam1 function with a dominant-negative Tiam1 mutant blocks
      dendritic spine formation induced by ephrinB1 stimulation. Taken together, these
      findings suggest that EphBs regulate spine development in part by recruiting,
      phosphorylating, and activating Tiam1. Tiam1 can then promote Rac1-dependent
      actin cytoskeletal remodeling required for dendritic spine morphogenesis.

PMID- 17440042
TI  - Self-organization of actin filament orientation in the dendritic-nucleation/array
      treadmilling model.
AB  - The dendritic-nucleation/array-treadmilling model provides a conceptual framework
      for the generation of the actin network driving motile cells. We have
      incorporated it into a 2D, stochastic computer model to study lamellipodia via
      the self-organization of filament orientation patterns. Essential dendritic
      nucleation submodels were incorporated, including discretized actin monomer
      diffusion, Monte-Carlo filament kinetics, and flexible filament and plasma
      membrane mechanics. Model parameters were estimated from the literature and
      simulation, providing values for the extent of the leading edge-branching/capping
      protective zone (5.4 nm) and the autocatalytic branch rate (0.43/sec). For a
      given set of parameters, the system evolved to a steady-state filament count and
      velocity, at which total branching and capping rates were equal only for specific
      orientations; net capping eliminated others. The standard parameter set evoked a
      sharp preference for the +/-35 degree filaments seen in lamellipodial electron
      micrographs, requiring approximately 12 generations of successive branching to
      adapt to a 15 degree change in protrusion direction. This pattern was robust with
      respect to membrane surface and bending energies and to actin concentrations but
      required protection from capping at the leading edge and branching angles >60
      degrees. A +70/0/-70 degree pattern was formed with flexible filaments
      approximately 100 nm or longer and with velocities < approximately 20% of free
      polymerization rates.

PMID- 17440044
TI  - Congenital hypothyroidism, dwarfism, and hearing impairment caused by a missense
      mutation in the mouse dual oxidase 2 gene, Duox2.
AB  - Dual oxidases generate the hydrogen peroxide needed by thyroid peroxidase for the
      incorporation of iodine into thyroglobulin, an essential step in thyroid hormone
      synthesis. Mutations in the human dual oxidase 2 gene, DUOX2, have been shown to
      underlie several cases of congenital hypothyroidism. We report here the first
      mouse Duox2 mutation, which provides a new genetic model for studying the
      specific function of DUOX2 in the thyroid gland and in other organ systems where
      it is hypothesized to play a role. We mapped the new spontaneous mouse mutation
      to chromosome 2 and identified it as a T>G base pair change in exon 16 of Duox2.
      The mutation changes a highly conserved valine to glycine at amino acid position
      674 (V674G) and was named "thyroid dyshormonogenesis" (symbol thyd) to signify a
      defect in thyroid hormone synthesis. Thyroid glands of mutant mice are goitrous
      and contain few normal follicles, and anterior pituitaries are dysplastic. Serum
      T(4) in homozygotes is about one-tenth the level of controls and is accompanied
      by a more than 100-fold increase in TSH. The weight of adult mutant mice is
      approximately half that of littermate controls, and serum IGF-I is reduced. The
      cochleae of mutant mice exhibit abnormalities characteristic of hypothyroidism,
      including a delayed formation of the inner sulcus and tunnel of Corti and an
      abnormally thickened tectorial membrane. Hearing thresholds of adult mutant mice
      are on average 50-60 decibels (dB) above those of controls.

PMID- 17440045
TI  - Regulation of hepatic Insig-2 by the farnesoid X receptor.
AB  - Activation of the farnesoid X receptor (FXRalpha) affects genes controlling many
      pathways, including those involved in bile acid and glucose homeostasis. Here we
      report that a critical gene involved in cholesterol homeostasis, Insig-2, was
      induced when mice or cultured cells were treated with FXRalpha agonists or
      infected with constitutively active FXRalpha. No such induction was observed in
      agonist-treated FXRalpha-/- mice. Further analysis, which included EMSAs,
      reporter gene activation, and chromatin immunoprecipitation, identified two
      functional FXRalpha response elements within intron 2 of the mouse Insig-2 gene.
      In addition to increasing hepatic Insig-2 protein levels in wild-type mice,
      FXRalpha activation also reduced lanosterol 14alpha-demethylase mRNA levels and 3
      hydroxy-3-methylglutaryl-coenzyme A reductase protein levels. Together, these
      changes likely account for the decrease in cholesterol synthesis observed after
      activation of FXR in primary hepatocytes. In conclusion, the current study links
      hepatic FXRalpha activation to regulation of genes involved in cholesterol
      synthesis.

PMID- 17440046
TI  - Cyclin-dependent kinase 5 differentially regulates the transcriptional activity
      of the glucocorticoid receptor through phosphorylation: clinical implications for
      the nervous system response to glucocorticoids and stress.
AB  - Glucocorticoids, major end effectors of the stress response, play an essential
      role in the homeostasis of the central nervous system and influence diverse
      functions of neuronal cells. We found that cyclin-dependent kinase 5 (CDK5),
      which plays important roles in the morphogenesis and functions of the nervous
      system and whose aberrant activation is associated with development of
      neurodegenerative disorders, interacted with the ligand-binding domain of the
      glucocorticoid receptor (GR) through its activator p35 or its active proteolytic
      fragment p25. CDK5 phosphorylated GR at multiple serines, including Ser203 and
      Ser211 of its N-terminal domain, and suppressed the transcriptional activity of
      this receptor on glucocorticoid-responsive promoters by attenuating attraction of
      transcriptional cofactors to DNA. In microarray analyses using rat cortical
      neuronal cells, the CDK5 inhibitor roscovitine differentially regulated the
      transcriptional activity of the GR on more than 90% of the endogenous
      glucocorticoid-responsive genes tested. Thus, CDK5 exerts some of its biological
      activities in neuronal cells through the GR, dynamically modulating GR
      transcriptional activity in a target promoter-dependent fashion.

PMID- 17440047
TI  - Progestin effects on breast cancer cell proliferation, proteases activation, and
      in vivo development of metastatic phenotype all depend on progesterone receptor
      capacity to activate cytoplasmic signaling pathways.
AB  - Accumulating evidence indicates that progestins are involved in controlling
      mammary gland tumorigenesis. Here, we assessed the molecular mechanisms of
      progestin action in breast cancer models with different phenotypes. We examined
      C4HD cells, an estrogen (ER) and progesterone (PR) receptor-positive murine
      breast cancer model in which progestins exert sustained proliferative response,
      the LM3 murine metastatic mammary tumor cell line, which lacks PR and ER
      expression, and human PR null T47D-Y breast cancer cells. In addition to acting
      as a transcription factor, PR can also function as an activator of signaling
      pathways. To explore which of these two functions were involved in progestin
      responses, reconstitution experiments in the PR-negative models were performed
      with wild-type PR-B, with a DNA binding mutant C587A-PR, and with mutant PR
      BmPro, which lacks the ability to activate cytoplasm signaling pathways. We found
      that in a cell context either ER-positive or -negative, progestins induced cell
      growth and modulation of matrix metalloproteinases-9 (MMP-9) and -2 (MMP-2), and
      urokinase-type plasminogen activator (uPA) activities, via MAPK and
      phosphatidylinositol 3-kinase/Akt pathways, in cells expressing wild-type PR-B or
      DNA binding mutant C587A-PR. In contrast, in cells expressing mutant PR-BmPro,
      progestins did not induce growth. We also found that unliganded PR expression
      conferred breast cancer cells an in vitro less proliferative phenotype, as
      compared with cells lacking PR expression. Modulation of this behavior occurred
      when PR was functioning either as transcription factor or as signaling activator.
      Finally, we for the first time demonstrated that progestins favor development of
      breast tumor metastasis via PR function as activator of signaling pathways. Our
      present findings provide mechanistic support to the design of a novel therapeutic
      intervention in PR-positive breast tumors involving blockage of PR capacity to
      activate cytoplasmic signaling.

PMID- 17440048
TI  - The incidence and clinical significance of nucleophosmin mutations in childhood
      AML.
AB  - Frameshift mutations in exon 12 of the nucleophosmin gene (NPM1) result in
      aberrant cytoplasmic localization of the NPM protein (NPMc(+)) and occur in 25%
      to 35% of adult acute myeloid leukemia (AML). In adults with AML, NPMc(+) has
      been associated with normal karyotype, FLT3/ITD mutations, high remission
      induction rates, and improved survival (particularly in patients lacking
      FLT3/ITD). NPMc(+) has not been well characterized in childhood AML. This study
      examines the incidence and clinical significance of NPMc(+) in 295 children with
      newly diagnosed AML treated on a large cooperative group clinical trial (POG
      9421). We find that NPMc(+) is relatively uncommon in childhood AML (23 of 295
      patients, 8%); and is significantly associated with FLT3/ITD mutations (P =
      .046), female sex (P = .029), older age (P = .047), and normal cytogenetics (P <
      .001). There is a favorable impact of NPMc(+) on survival in children lacking
      FLT3/ITD (5-year EFS, 69% vs 35%; hazard ratio, 0.39; P = .051), which is similar
      in magnitude to the favorable impact of t(8;21) and inv(16). We conclude that
      NPMc(+) is relatively rare in childhood AML, particularly in younger children.
      NPMc(+) does not abrogate the negative prognostic influence of FLT3/ITD
      mutations, but may contribute to risk stratification in children who lack
      FLT3/ITD mutations by identifying a group with superior prognosis.

PMID- 17440049
TI  - Clinical significance of different antiphospholipid antibodies in the WAPS
      (warfarin in the antiphospholipid syndrome) study.
AB  - To assess the clinical significance of lupus anticoagulants (LAs) and
      antiphospholipid antibodies (aPLs) toward thrombosis and abortions, we measured
      them in 112 patients whose samples were available at enrollment in the warfarin
      in the antiphospholipid syndrome (WAPS) study. Enzyme-linked immunosorbent assay
      (ELISA) and coagulation test values in the highest and lowest tertiles were
      compared. When considered separately, IgG antibodies to beta2-glycoprotein I
      (abeta2GPI) and prothrombin (aPT) were associated with anamnestic arterial and
      venous thrombosis, respectively, and those to annexin AV (aAnAV) with abortions.
      IgM antibodies to protein S and the lupus ratio of the dilute prothrombin time
      were associated with prospective thrombosis. No other association for IgM
      antibodies was seen. LA-positive patients who carried abeta2GPI antibodies were
      at risk of anamnestic arterial and total thrombosis and aPT antibodies to that of
      anamnestic venous and total thrombosis. LA-positive patients who carried IgG
      abeta2GPI and aAnAV antibodies were at risk for both anamnestic abortion and
      prospective thrombosis. Overall, these data support the inclusion of abeta2GPI
      antibodies in and suggest the removal of anticardiolipin antibodies from the
      laboratory criteria of the antiphospholipid syndrome. They also suggest that the
      measurement of aPT and aAnAV antibodies is useful in some selected situations and
      that there is little role for IgM antibody detection.

PMID- 17440050
TI  - Human cytomegalovirus sequences expressed in latently infected individuals
      promote a latent infection in vitro.
AB  - Latency enables human cytomegalovirus (HCMV) to persist in the hematopoietic
      cells of infected individuals indefinitely and prevents clearance of the
      pathogen. Despite its critical importance to the viral infectious cycle, viral
      mechanisms that contribute to latency have not been identified. We compared the
      ability of low-passage clinical and laboratory-adapted strains of HCMV to
      establish a latent infection in primary human CD34(+) cells. The low-passage
      strains, Toledo and FIX, established an infection with the hallmarks of latency,
      whereas the laboratory strains, AD169 and Towne, replicated producing progeny
      virus. We hypothesized that ULb' region of the genome, which is unique to low
      passage strains, may encode a latency-promoting activity. We created and analyzed
      recombinant viruses lacking segments or individual open reading frames (ORFs) in
      the ULb' region. One 5-kb segment, and more specifically the UL138 ORF, was
      required for HCMV to establish and/or maintain a latent infection in
      hematopoietic progenitor cells infected in vitro. This is the first functional
      demonstration of a virus-coded sequence required for HCMV latency. Importantly,
      UL138 RNA was expressed in CD34(+) cells and monocytes from HCMV-seropositive,
      healthy individuals. UL138 might be a target for antivirals against latent virus.

PMID- 17440051
TI  - SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have
      impaired proliferative capacity in acute and chronic SIVmac251 infection.
AB  - Programmed death-1 (PD-1) is a critical mediator of virus-specific CD8+ T-cell
      exhaustion. Here, we examined the expression of PD-1 on simian immunodeficiency
      virus (SIV)-specific CD8+ T cells and its possible involvement in regulation of
      cytokine production, proliferation, and survival of these cells. The majority of
      SIV-specific CD8+ T cells expressed a PD-1(high) phenotype, independent of their
      differentiation status, in all tissues tested. PD-1 expression gradually declined
      on CD8+ T cells specific for SIV-derived epitopes that had undergone mutational
      escape, indicating that antigen-specific TCR stimulation is the primary
      determinant of PD-1 expression. SIV-specific PD-1(high)CD8+ T cells produced IFN
      gamma, TNF-alpha, and IL-2 under cognate peptide stimulation. While CD8+ T cells
      that proliferated in response to antigen had a PD-1(high) phenotype, it was
      determined that there was a reduced proliferative capacity of PD-1(high) compared
      with PD-1(low) SIV-specific CD8+ T cells. PD-1(high) SIV-specific CD8+ T cells
      were highly susceptible to cell death leading to loss of such cells after in
      vitro stimulation. Thus, PD-1 is a negative regulator of SIV-specific CD8+ T
      cells, operating predominantly through the induction of cell death. Manipulation
      of the interaction of PD-1 with its ligands could thus potentially restore the
      CD8+ T-cell responses in SIV infection.

PMID- 17440052
TI  - Targeting CD37-positive lymphoid malignancies with a novel engineered small
      modular immunopharmaceutical.
AB  - CD37 is a lineage-specific B-cell antigen that to date has been neglected as an
      attractive therapeutic target. To exploit this, novel CD37-specific small modular
      immunopharmaceuticals (CD37-SMIP) that include variable regions linked to
      modified human IgG(1) hinge, CH(2), and CH(3) domains were designed. The lead
      CD37-SMIP molecule induces potent apoptosis in the presence of a cross-linker,
      and antibody-dependent cellular cytotoxicity against B-cell leukemia/lymphoma
      cell lines and primary chronic lymphocytic leukemia (CLL) cells superior to
      therapeutic antibodies used in these diseases. The CD37-SMIP-dependent ADCC
      function in vitro was mediated by natural killer (NK) cells but not naive or
      activated monocytes. Significant in vivo therapeutic efficacy was demonstrated in
      a SCID mouse xenograft leukemia/lymphoma model. Depletion of NK cells in this
      mouse model resulted in diminished efficacy further supported the in vivo
      importance of NK cells in SMIP therapy. These findings provide strong
      justification for CD37 as a therapeutic target and introduce small modular
      immunopharmaceuticals as a novel class of targeted therapies for B-cell
      malignancies.

PMID- 17440053
TI  - Mutagen sensitivity: a genetic predisposition factor for cancer.
AB  - Mutagen sensitivity, measured by quantifying the chromatid breaks induced by
      mutagens in short-term cultures of peripheral blood lymphocytes, has been used as
      an indirect measure of DNA repair capacity. Numerous epidemiologic studies have
      suggested that mutagen sensitivity is a cancer susceptibility factor for a
      variety of epithelial cancers. A recent classic twin study examined
      systematically the role of genetic and environmental factors on the mutagen
      sensitivity phenotype and provided compelling evidence that mutagen sensitivity
      is highly heritable. A new prospective analysis provides further support to the
      notion that mutagen sensitivity increases the risk of cancer. In this review, we
      briefly summarize nearly two decades of epidemiologic and genetic studies linking
      mutagen sensitivity and cancer risk. The evidence is becoming increasingly
      convincing that mutagen sensitivity is a risk factor for cancer development.

PMID- 17440054
TI  - GRP78 induction in cancer: therapeutic and prognostic implications.
AB  - Cancer cells adapt to chronic stress in the tumor microenvironment by inducing
      the expression of GRP78/BiP, a major endoplasmic reticulum chaperone with Ca(2+)
      binding and antiapoptotic properties. GRP78 promotes tumor proliferation,
      survival, metastasis, and resistance to a wide variety of therapies. Thus, GRP78
      expression may serve as a biomarker for tumor behavior and treatment response.
      Combination therapy suppressing GRP78 expression may represent a novel approach
      toward eradication of residual tumors. Furthermore, the recent discovery of GRP78
      on the cell surface of cancer cells but not in normal tissues suggests that
      targeted therapy against cancer via surface GRP78 may be feasible.

PMID- 17440055
TI  - Coordinated regulation of pathways for enhanced cell motility and chemotaxis is
      conserved in rat and mouse mammary tumors.
AB  - Correlating tumor cell behavior in vivo with patterns of gene expression has led
      to new insights into the microenvironment of tumor cells in the primary tumor.
      Until now, these studies have been done with cell line-derived tumors. In the
      current study, we have analyzed, in polyoma middle T oncogene (PyMT)-derived
      mammary tumors, tumor cell behavior and gene expression patterns of the invasive
      subpopulation of tumor cells by multiphoton-based intravital imaging and
      microarray-based expression profiling, respectively. Our results indicate that
      the patterns of cell behavior that contribute to invasion and metastasis in the
      PyMT tumor are similar to those seen previously in rat MTLn3 cell line-derived
      mammary tumors. The invasive tumor cells collected from PyMT mouse mammary
      tumors, like their counterparts from rat xenograft mammary tumors, are a
      population that is relatively nondividing and nonapoptotic but chemotherapy
      resistant and chemotactic. Changes in the expression of genes that occur uniquely
      in the invasive subpopulation of tumor cells in the PyMT mammary tumors that fall
      on the Arp2/3 complex, capping protein and cofilin pathways show a pattern like
      that seen previously in invasive tumor cells from the MTLn3 cell line-derived
      tumors. These changes predict an enhanced activity of the cofilin pathway, and
      this was confirmed in isolated invasive PyMT tumor cells. We conclude that
      changes in gene expression and their related changes in cell behavior, which were
      identified in the invasive tumor cells of cell line-derived tumors, are conserved
      in the invasive tumor cells of PyMT-derived mouse mammary tumors, although these
      tumor types have different genetic origins.

PMID- 17440056
TI  - Novel action of paclitaxel against cancer cells: bystander effect mediated by
      reactive oxygen species.
AB  - Generation of reactive oxygen species (ROS) has been observed in cancer cells
      treated with paclitaxel, but the underlying mechanisms and therapeutic
      implications remain unclear. In the present study, we showed that paclitaxel
      promoted ROS generation through enhancing the activity of NADPH oxidase (NOX)
      associated with plasma membranes. Treatment of breast cancer cells caused an
      increased translocation of Rac1, a positive regulatory protein of NOX, to the
      membrane fraction. The paclitaxel-induced ROS generation occurred rapidly within
      several hours of drug exposure, with O(2)(-) and H(2)O(2) accumulation mainly
      outside the cells while the intracellular ROS remained unchanged. Importantly,
      the increase in extracellular ROS caused lethal damage to the bystander cancer
      cells not exposed to paclitaxel, as shown by two different methods using
      coculture systems where the bystander cells were differentiated from the
      paclitaxel-treated cells by fluorescent or radioactive labeling. This cytotoxic
      bystander effect was also observed with other microtubule-targeted agents
      vincristine and taxotere but not with 5-fluorouracil or doxorubicin. This toxic
      bystander effect was enhanced by CuZnSOD that converts O(2)(-) to H(2)O(2) and
      was abolished by a catalase that eliminates H(2)O(2). Furthermore, paclitaxel was
      able to induce an almost complete inhibition of proliferation of the bystander
      cells in the coculture system. Our study revealed a novel mechanism by which
      paclitaxel induces toxic bystander effect through generation of extracellular
      H(2)O(2) from the membrane-associated NOX. This may contribute to the potent
      anticancer activity of paclitaxel and provide a novel basis to improve the
      clinical use of this important drug.

PMID- 17440057
TI  - Identification of their epitope reveals the structural basis for the mechanism of
      action of the immunosuppressive antibodies basiliximab and daclizumab.
AB  - Interleukin-2 (IL-2) and its receptor (IL-2R) play a major role in cellular
      immunity. The monoclonal antibodies basiliximab and daclizumab directed against
      the IL-2R subunit CD25 are widely used to prevent graft or host rejection after
      allogeneic tissue transplantation. Although these antibodies have been used for
      this purpose for many years, their common epitope within the CD25 protein is
      unknown. We screened a random phage display library to isolate peptides
      specifically binding to basiliximab. A striking amino acid sequence motif was
      enriched. This motif is homologous to the peptide ERIYHFV comprising amino acid
      positions 116 to 122 within the extracellular domain of CD25, suggesting that
      this is the basiliximab epitope. Basiliximab and daclizumab binding of selected
      phage was specific, as no binding was observed to isotype antibody controls.
      Phage binding could be inhibited by the cognate peptide. In cells expressing
      mutant CD25, binding of basiliximab was abolished when two or more amino acids of
      the suspected epitope were changed. In contrast, basiliximab binding remained
      unaffected in cells expressing CD25 versions with mutations outside this epitope.
      We therefore conclude that the (116)ERIYHFV(122) string within CD25 is the
      epitope recognized by basiliximab and daclizumab. This epitope overlaps with the
      interaction site of CD25 and IL-2, thus revealing the structural basis for the
      inhibition of IL-2R binding by this class of immunosuppressive antibodies.

PMID- 17440058
TI  - An imaging biomarker of early treatment response in prostate cancer that has
      metastasized to the bone.
AB  - Prostate cancer ranks as the most common lethal malignancy diagnosed and the
      second leading cause of cancer mortality in American men. Although high response
      rates are achieved using androgen blockade as first-line therapy, most men
      progress toward hormone-refractory prostate cancer. Systemic chemotherapies have
      been shown to improve clinical outcome in hormone refractory prostate cancer
      patients; however, they are not curative. Due to the high incidence of bone
      involvement in hormone-refractory prostate cancer, assessment of treatment
      response in metastatic prostate cancer to the bone remains a major clinical need.
      In this current study, we investigated the feasibility of using the functional
      diffusion map (fDM) as an imaging biomarker for assessing early treatment
      response in a preclinical model of metastatic prostate cancer. The fDM biomarker
      requires a pretreatment and midtreatment magnetic resonance imaging diffusion
      map, which is used to quantify spatially distinct therapeutic-induced changes in
      the Brownian motion (or diffusion) of water within tumor tissue. Because water
      within tumor cells is in a restricted environment relative to extracellular
      water, loss of cell membrane integrity and cellular density during therapy will
      be detected by fDM as an increase in diffusion. Regions of significantly
      increased diffusion values were detected early using fDM in docetaxel-treated
      versus untreated metastatic prostate bone tumors at 7 days post treatment
      initiation (P < 0.05), indicating loss of tumor cell viability. Validation of fDM
      results was accomplished by histologic analysis of excised tissue. Results from
      this study show the capability of fDM as a biomarker for detection of bone cancer
      treatment efficacy, thus warranting clinical evaluation.

PMID- 17440059
TI  - A selective small molecule inhibitor of c-Met, PHA665752, inhibits tumorigenicity
      and angiogenesis in mouse lung cancer xenografts.
AB  - The c-Met receptor tyrosine kinase is emerging as a novel target in many solid
      tumors, including lung cancer. PHA-665752 was identified as a small molecule, ATP
      competitive inhibitor of the catalytic activity of the c-Met kinase. Here, we
      show that treatment with PHA665752 reduced NCI-H69 (small cell lung cancer) and
      NCI-H441 (non-small cell lung cancer) tumorigenicity in mouse xenografts by 99%
      and 75%, respectively. Reduction in tumor size was also observed by magnetic
      resonance imaging of tumors in mice. PHA665752 inhibited c-Met phosphorylation at
      the autophosphorylation and c-Cbl binding sites in mouse xenografts derived from
      non-small cell lung cancer cell lines (NCI-H441 and A549) and small cell lung
      cancer cell line (NCI-H69). PHA665752 also inhibited angiogenesis by >85% in all
      the abovementioned cell lines and caused an angiogenic switch which resulted in a
      decreased production of vascular endothelial growth factor and an increase in the
      production of the angiogenesis inhibitor thrombospondin-1. These studies show the
      feasibility of selectively targeting c-Met with ATP competitive small molecule
      inhibitors and suggest that PHA665752 may provide a novel therapeutic approach to
      lung cancer.

PMID- 17440060
TI  - Elucidating the function of secreted maspin: inhibiting cathepsin D-mediated
      matrix degradation.
AB  - Cellular interaction with the extracellular milieu plays a significant role in
      normal biological and pathologic processes. Excessive degradation of basement
      membrane matrix by proteolytic enzymes is a hallmark of tumor invasion and
      metastasis, and aspartyl proteinase cathepsin D is implicated as a major
      contributor to this process. Maspin, a non-inhibitory serpin, plays an important
      role in mammary gland development and remodeling. Expression of Maspin is
      decreased in primary tumors and lost in metastatic lesions. Maspin is mostly
      cytoplasmic and is partially secreted; however, the fate and function of secreted
      Maspin has remained mostly unexplored. We hypothesized that secreted Maspin is
      incorporated into the matrix deposited by normal mammary epithelial cells and
      thus could play a critical role in cathepsin D-mediated matrix degradation and
      remodeling of mammary tissue. In the absence of Maspin, as is the case with most
      cancer cells, matrix degradation proceeds unrestricted, thus facilitating the
      progression to metastasis. To test this, we employed an in vitro model where gels
      containing both types I and IV collagen were preconditioned with normal mammary
      epithelial cells to allow the incorporation of secreted Maspin. This conditioned
      matrix was used to examine cathepsin D-mediated collagen degradation by human
      breast cancer cell lines. Our results indicate that secretion of Maspin and its
      deposition into the extracellular milieu play an important role in matrix
      degradation. In this capacity, Maspin could potentially regulate mammary tissue
      remodeling occurring under normal and pathologic conditions. In addition, these
      findings could have a potential effect on future therapeutic intervention
      strategies for breast cancer.

PMID- 17440061
TI  - Malignant glioma cells counteract antitumor immune responses through expression
      of lectin-like transcript-1.
AB  - Glioblastoma, one of the most lethal tumors, is paradigmatic for tumor-associated
      immunosuppression. Lectin-like transcript-1 (LLT1) is a newly identified ligand
      for the inhibitory natural killer (NK) cell receptor CD161. Here, we report that
      glioma cells express LLT1 mRNA and protein in vitro and in vivo, whereas
      expression levels in normal brain are low. LLT1 expression in human gliomas
      increases with the WHO grade of malignancy. We further show that transforming
      growth factor-beta (TGF-beta) up-regulates the expression of LLT1 in glioma
      cells. Small interfering RNA (siRNA)-mediated down-regulation of LLT1 in LNT-229
      and LN-428 cells promotes their lysis by NK cells. Thus, LLT1 acts as a mediator
      of immune escape and contributes to the immunosuppressive properties of glioma
      cells.

PMID- 17440062
TI  - Novel somatic and germline mutations in cancer candidate genes in glioblastoma,
      melanoma, and pancreatic carcinoma.
AB  - A recent systematic sequence analysis of well-annotated human protein coding
      genes or consensus coding sequences led to the identification of 189 genes
      displaying somatic mutations in breast and colorectal cancers. Based on their
      mutation prevalence, a subset of these genes was identified as cancer candidate
      (CAN) genes as they could be potentially involved in cancer. We evaluated the
      mutational profiles of 19 CAN genes in the highly aggressive tumors:
      glioblastoma, melanoma, and pancreatic carcinoma. Among other changes, we found
      novel somatic mutations in EPHA3, MLL3, TECTA, FBXW7, and OBSCN, affecting amino
      acids not previously found to be mutated in human cancers. Interestingly, we also
      found a germline nucleotide variant of OBSCN that was previously reported as a
      somatic mutation. Our results identify specific genetic lesions in glioblastoma,
      melanoma, and pancreatic cancers and indicate that CAN genes and their mutational
      profiles are tumor specific. Some of the mutated genes, such as the tyrosine
      kinase EPHA3, are clearly amenable to pharmacologic intervention and could
      represent novel therapeutic targets for these incurable cancers. We also
      speculate that similar to other oncogenes and tumor suppressor genes, mutations
      affecting OBSCN could be involved in cancer predisposition.

PMID- 17440063
TI  - Mutations in BRAF and KRAS differentially distinguish serrated versus non
      serrated hyperplastic aberrant crypt foci in humans.
AB  - We previously reported that colon carcinomas, adenomas, and hyperplastic polyps
      exhibiting a serrated histology were very likely to possess BRAF mutations,
      whereas when these same advanced colonic lesions exhibited non-serrated
      histology, they were wild type for BRAF; among hyperplastic polyps, KRAS
      mutations were found mainly in a non-serrated variant. On this basis, we
      predicted that hyperplastic aberrant crypt foci (ACF), a putative precancerous
      lesion found in the colon, exhibiting a serrated phenotype would also harbor BRAF
      mutations and that non-serrated ACF would not. In contrast, KRAS mutations would
      be found more often in the non-serrated ACF. We examined 55 ACF collected during
      screening colonoscopy from a total of 28 patients. Following laser capture
      microdissection, DNA was isolated, and mutations in BRAF and KRAS were determined
      by direct PCR sequencing. When hyperplastic lesions were further classified into
      serrated and non-serrated histologies, there was a strong inverse relationship
      between BRAF and KRAS mutations: a BRAF(V600E) mutation was identified in 10 of
      16 serrated compared with 1 of 33 non-serrated lesions (P = 0.001); conversely,
      KRAS mutations were present in 3 of 16 serrated compared with 14 of 33 non
      serrated lesions. Our finding of a strong association between BRAF mutations and
      serrated histology in hyperplastic ACF supports the idea that these lesions are
      an early, sentinel, or a potentially initiating step on the serrated pathway to
      colorectal carcinoma.

PMID- 17440064
TI  - Shared MHC class II-dependent melanoma ribosomal protein L8 identified by phage
      display.
AB  - Antigens recognized by T helper (Th) cells in the context of MHC class II
      molecules have vaccine potential against cancer and infectious agents. We have
      described previously a melanoma patient's HLA-DR7-restricted Th cell clone
      recognizing an antigen, which is shared among melanoma and glioma cells derived
      from various patients. Here, this antigen was cloned using a novel antigen phage
      display approach. The antigen was identified as the ribosomal protein L8 (RPL8).
      A peptide of RPL8 significantly stimulated proliferation and/or cytokine
      expression of the Th cell clone and lymphocytes in four of nine HLA-DR7(+)
      melanoma patients but not in healthy volunteers. The RPL8 antigen may represent a
      relevant vaccine target for patients with melanoma, glioma, and breast carcinoma
      whose tumors express this protein.

PMID- 17440065
TI  - Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects
      reduce the tumor stem-like cell fraction in glioma xenograft tumors.
AB  - Vascular endothelial cells have been identified as a critical component of the
      neural stem cell niche, raising the possibility that brain tumor stem-like cells
      (TSLC) may also rely on signaling interactions with nearby tumor vasculature to
      maintain their stem-like state. The disruption of such a TSLC vascular niche by
      an antiangiogenic therapy could result in loss of stemness characteristics
      associated with intrinsic drug resistance and, thus, preferentially sensitize
      TSLC to the effects of chemotherapy. Considering these possibilities, we
      investigated the impact of antiangiogenic anticancer therapy on the TSLC fraction
      of glioma tumors. Athymic nude mice bearing s.c. tumor xenografts of the C6 rat
      glioma cell line were treated with either a targeted antiangiogenic agent,
      antiangiogenic schedules of low-dose metronomic chemotherapy, combination
      therapies of antiangiogenic agents and chemotherapy, or, for the purpose of
      comparison, a conventional cytotoxic schedule of maximum tolerated dose
      chemotherapy using cyclophosphamide. Targeted antiangiogenic therapy or cytotoxic
      chemotherapy did not reduce the fraction of tumor sphere-forming units (SFU) in
      the tumor, whereas all treatment groups that combined both antiangiogenic and
      cytotoxic drug effects caused a significant reduction in SFU. This work
      highlights the possibility that selective eradication of TSLC may be achieved by
      targeting the tumor microenvironment (and potentially a supportive TSLC niche)
      rather than the TSLC directly. Furthermore, this work suggests a possible novel
      effect of antiangiogenic therapy, namely, as a chemosensitizer of TSLC, and thus
      represents a possible new mechanism to explain the ability of antiangiogenic
      therapy to enhance the efficacy of chemotherapy.

PMID- 17440066
TI  - A variant in the cytochrome p450 oxidoreductase gene is associated with breast
      cancer risk in African Americans.
AB  - Variation in the cytochrome P450 oxidoreductase (POR) gene, a key regulator of
      type II cytochrome P450 enzymes, may affect exposure to endogenous steroid
      hormones and breast cancer risk. We sequenced the POR locus and tested candidate
      polymorphisms G5G and A503V for association with breast cancer risk among women
      in the Multiethnic Cohort Study (1,615 cases and 1,962 controls). The single
      nucleotide polymorphism (SNP) A503V was common in all racial/ethnic populations
      (minor allele frequency, > or =0.05) but was not associated with risk. SNP G5G (A
      --> G nucleotide change), which lies in a suggestive exonic splicing enhancer
      motif in exon 1, was common only in African Americans (minor allele frequency,
      0.21) and the homozygous state was modestly associated with increased breast risk
      among all cases [345 cases and 426 controls; odds ratio (OR), 1.64; 95%
      confidence interval (CI), 0.89-3.04; P = 0.12] and among cases with advanced
      disease (95 cases: OR, 3.08; 95% CI, 1.42-6.70; P = 0.005). In an attempt to
      replicate this association, we genotyped SNP G5G in additional African American
      case-control studies (747 cases and 468 controls). Nonsignificant positive
      associations were noted with the GG genotype class in all studies. In the pooled
      analysis (1,038 cases and 877 controls with genotype data), the association was
      statistically significant among all cases (OR, 1.58; 95% CI, 1.04-2.41; P = 0.03)
      and stronger in those with advanced disease (411 cases and 877 controls; OR,
      2.60; 95% CI, 1.56-4.34; P = 0.0002). These data suggest that African Americans
      harbor an allele at the POR locus that may increase breast cancer risk.

PMID- 17440067
TI  - Phenethyl isothiocyanate, a cancer chemopreventive constituent of cruciferous
      vegetables, inhibits cap-dependent translation by regulating the level and
      phosphorylation of 4E-BP1.
AB  - Phenethyl isothiocyanate (PEITC), a constituent of many edible cruciferous
      vegetables, exerts significant protection against chemically induced cancer in
      animal models and inhibits growth of cancer cells in culture and in vivo by
      causing cell cycle arrest and apoptosis induction. In this study, we report a
      novel response to PEITC involving the regulation of translation initiation at
      pharmacologically achievable concentrations. Treatment of human colorectal cancer
      HCT-116 cells and human prostate cancer PC-3 cells, but not a normal prostate
      epithelial cell line (PrEC), with PEITC caused an increase in expression of the
      eukaryotic translation initiation factor 4E (eIF4E) binding protein (4E-BP1) and
      inhibition of 4E-BP1 phosphorylation. Results from pull-down assay using 7-methyl
      GTP Sepharose 4B beads indicated that PEITC treatment reduced cap-bound eIF4E,
      confirming that increased 4E-BP1 expression and inhibition of 4E-BP1
      phosphorylation indeed reduced the availability of eIF4E for translation
      initiation. Accordingly, results from in vivo translation using luciferase
      reporter assay indicated that PEITC treatment inhibited cap-dependent
      translation, in particular the translation of mRNA with secondary structure (stem
      loop structure). Ectopic expression of eIF4E prevented PEITC-induced translation
      inhibition and conferred significant protection against PEITC-induced apoptosis.
      These results indicate that PEITC modulates availability of eIF4E for translation
      initiation leading to inhibition of cap-dependent translation. The present study
      also suggests that inhibition of cap-dependent translation may be an important
      mechanism in PEITC-induced apoptosis.

PMID- 17440068
TI  - TIP30 mutant derived from hepatocellular carcinoma specimens promotes growth of
      HepG2 cells through up-regulation of N-cadherin.
AB  - TIP30 is a tumor suppressor whose expression is altered in human liver, prostate,
      lung, colon, and breast cancers. Mice lacking TIP30 spontaneously developed
      hepatocellular carcinomas (HCC) and other tumors at a higher incidence than wild
      type mice. Somatic missense mutations in the TIP30 gene were identified in human
      HCC tissue specimens, which resulted in instability or abnormal cellular
      distribution of TIP30 protein in cells. Here, we show that TIP30 mutants are able
      to promote cell growth and invasion and inhibit cisplatin-induced apoptosis in
      the HCC cell line HepG2 negative for endogenous TIP30. Moreover, one of the TIP30
      mutants can dramatically accelerate tumor formation in immunodeficient mice.
      Analysis of gene expression in HepG2 cells, ectopically expressing either wild
      type TIP30 or mutant TIP30, by Affymetrix GeneChip array, real-time quantitative
      PCR, and Western blotting assays reveals that TIP30 mutants can alter expression
      of genes involved in the regulation of tumorigenesis. This includes up-regulation
      of expression of N-cadherin and c-MYC and down-regulation of expression of p53
      and E-cadherin. N-cadherin knockdown with small interfering RNA in HepG2 cells
      expressing mutant TIP30 resulted in a profound reduction in cell viability. Taken
      together, our data indicate that somatic mutations in the TIP30 gene may abolish
      its native tumor-suppressor activity and gain oncogenic activities partially
      through up-regulation of N-cadherin, thereby potentiating the pathogenesis of HCC
      in patients.

PMID- 17440069
TI  - Selective down-regulation of glioma-associated oncogene 2 inhibits the
      proliferation of hepatocellular carcinoma cells.
AB  - The sonic hedgehog (Shh) pathway contributes to the initiation and progression of
      tumors with various origins when aberrantly activated. In this study, we
      investigated if the Shh pathway is important for the proliferation of
      hepatocellular carcinoma (HCC) cells and also began to identify which components
      of the pathway play a pivotal role in the biology of HCC. Expression levels of
      components in the pathway were measured, and glioma-associated oncogene (Gli) 2
      levels were found to be considerably higher in human HCC lines compared with
      normal liver. Gli2 levels were also higher in tumor tissue from HCC patients
      compared with normal liver. Antisense oligonucleotides (ASO) were used to
      specifically down-regulate Gli2, and this led to decreased proliferation of
      various HCC cell lines. However, inhibition of Gli1 and Gli3 with ASOs did not
      decrease proliferation in most HCC cell lines and inhibitors targeting the
      upstream components of the pathway, including smoothened (Smo), displayed
      antiproliferative effects in only a subset of HCC cell lines. Moreover, in cancer
      cells harboring Smo mutations or unresponsive to the Smo inhibitor 3-keto-N
      aminoethylaminoethylcaproyldihydrocinnamoyl cyclopamine, the Gli2 ASO was still
      able to inhibit proliferation. The importance of Gli2 in HCC proliferation was
      further confirmed by the changes in expression levels of genes, such as Bcl-2, c
      Myc, and p27, following suppression of Gli2 expression. Taken together, these
      results suggest that, among the Gli transcription factors, Gli2 plays a
      predominant role in the proliferation of HCC cells and the suppression of Gli2
      expression may provide a useful therapeutic option for the treatment of HCC.

PMID- 17440070
TI  - Cancer cell lines as genetic models of their parent histology: analyses based on
      array comparative genomic hybridization.
AB  - Tumor-derived cell lines are used as in vitro cancer models, but their ability to
      accurately reflect the phenotype and genotype of the parental histology remains
      questionable, given the prevalence of documented cell line-specific cytogenetic
      changes. We have addressed the issue of whether copy number alterations seen in
      tumor-derived cell lines reflect those observed in studies of fresh tissue by
      carrying out a meta-analysis of array-based comparative genomic hybridization
      data that considers both copy number alteration frequencies and the occurrence of
      cancer gene amplifications and homozygous deletions. Pairwise correlation
      comparisons between the data sets of seven diagnosis-specific matched tumor and
      cell line groups indicate that the trends in aberration frequencies are highly
      correlated between tumors and cell line sets of matched cancer histology relative
      to unmatched pairings. Despite their similarities, cell lines showed uniformly
      higher locus-specific alteration frequencies (P = 0.004) and several recurring
      cell line-specific alterations emerged. These include the previously documented
      losses of 13q and 9p and gains of 20q, as well as additional undescribed cell
      line-specific gains of 5p, 7p, and 17q and losses of 18q and 4q. These results
      indicate that, on average, cell lines preserve in vitro the genetic aberrations
      that are unique to the parent histology from which they were derived while
      acquiring additional locus-specific alterations. These data may enable a more
      predictive understanding of individual cell lines as in vitro models of cancer
      biology and therapy.

PMID- 17440071
TI  - P21-activated protein kinase is overexpressed in hepatocellular carcinoma and
      enhances cancer metastasis involving c-Jun NH2-terminal kinase activation and
      paxillin phosphorylation.
AB  - Hepatocellular carcinoma (HCC) is one of the major malignancies in the world. The
      prognosis of HCC is poor, due to frequent intrahepatic metastasis and tumor
      recurrence. P21-activated protein kinase (Pak1), a main downstream effector of
      small Rho GTPases, Rac1 and Cdc42, plays an important role in the regulation of
      cell morphogenesis, motility, mitosis, and angiogenesis. Here, we show that Pak1
      gene was overexpressed in human HCCs. Overexpression of Pak1 in human HCCs was
      associated with more aggressive tumor behavior in terms of more metastatic
      phenotype and more advanced tumor stages. In addition, HCC cell line stably
      expressing Pak1 displayed increased cell motility rates and, conversely,
      knockdown of endogenous Pak1 expression by small interfering RNA reduced the
      migration rates of HCC cells. In an established metastatic HCC cell line, we
      found that Pak1 was overexpressed compared with its primary HCC cell line and
      this overexpression was associated with higher cell motility. Importantly, we
      found that c-Jun NH(2)-terminal kinase (JNK) was activated in HCC cell lines
      overexpressing Pak1. Inhibition of the JNK activity by chemical inhibitor
      significantly reduced the migration rates of HCC cells via attenuation of
      paxillin phosphorylation at Ser(178). In conclusion, our results document that
      Pak1 is overexpressed in HCCs and plays an important role in the metastasis of
      HCC. The mechanism by which Pak1 induces cancer metastasis may involve activation
      of JNK and phosphorylation of paxillin.

PMID- 17440072
TI  - Huntingtin interacting protein 1 is a novel brain tumor marker that associates
      with epidermal growth factor receptor.
AB  - Huntingtin interacting protein 1 (HIP1) is a multidomain oncoprotein whose
      expression correlates with increased epidermal growth factor receptor (EGFR)
      levels in certain tumors. For example, HIP1-transformed fibroblasts and HIP1
      positive breast cancers have elevated EGFR protein levels. The combined
      association of HIP1 with huntingtin, the protein that is mutated in Huntington's
      disease, and the known overexpression of EGFR in glial brain tumors prompted us
      to explore HIP1 expression in a group of patients with different types of brain
      cancer. We report here that HIP1 is overexpressed with high frequency in brain
      cancers and that this overexpression correlates with EGFR and platelet-derived
      growth factor beta receptor expression. Furthermore, serum samples from patients
      with brain cancer contained anti-HIP1 antibodies more frequently than age-matched
      brain cancer-free controls. Finally, we report that HIP1 physically associates
      with EGFR and that this association is independent of the lipid, clathrin, and
      actin interacting domains of HIP1. These findings suggest that HIP1 may up
      regulate or maintain EGFR overexpression in primary brain tumors by directly
      interacting with the receptor. This novel HIP1-EGFR interaction may work with or
      independent of HIP1 modulation of EGFR degradation via clathrin-mediated membrane
      trafficking pathways. Further investigation of HIP1 function in brain cancer
      biology and validation of its use as a prognostic or predictive brain tumor
      marker are now warranted.

PMID- 17440073
TI  - SAG/ROC2/Rbx2 is a novel activator protein-1 target that promotes c-Jun
      degradation and inhibits 12-O-tetradecanoylphorbol-13-acetate-induced neoplastic
      transformation.
AB  - SAG (sensitive to apoptosis gene) was first identified as a stress-responsive
      protein that, when overexpressed, inhibited apoptosis both in vitro and in vivo.
      SAG was later found to be the second family member of ROC1 or Rbx1, a RING
      component of SCF and DCX E3 ubiquitin ligases. We report here that SAG/ROC2/Rbx2
      is a novel transcriptional target of activator protein-1 (AP-1). AP-1 bound both
      in vitro and in vivo to two consensus binding sites in a 1.3-kb region of the
      mouse SAG promoter. The SAG promoter activity, as measured by luciferase reporter
      assay, was dependent on these sites. Consistently, endogenous SAG is induced by
      12-O-tetradecanoylphorbol-13-acetate (TPA) with an induction time course
      following the c-Jun induction in both mouse epidermal JB6-Cl.41 and human 293
      cells. TPA-mediated SAG induction was significantly reduced in JB6-Cl.41 cells
      overexpressing a dominant-negative c-Jun, indicating a requirement of c-Jun/AP-1.
      On the other hand, SAG seemed to modulate the c-Jun levels. When overexpressed,
      SAG remarkably reduced both basal and TPA-induced c-Jun levels, whereas SAG small
      interfering RNA (siRNA) silencing increased substantially the levels of both
      basal and TPA-induced c-Jun. Consistently, SAG siRNA silencing reduced c-Jun
      polyubiquitination and blocked c-Jun degradation induced by Fbw7, an F-box
      protein of SCF E3 ubiquitin ligase. Finally, SAG overexpression inhibited,
      whereas SAG siRNA silencing enhanced, respectively, the TPA-induced neoplastic
      transformation in JB6-Cl.41 preneoplastic model. Thus, AP-1/SAG establishes an
      autofeedback loop, in which on induction by AP-1, SAG promotes c-Jun
      ubiquitination and degradation, thus inhibiting tumor-promoting activity of AP-1.

PMID- 17440074
TI  - PRAS40 deregulates apoptosis in malignant melanoma.
AB  - Malignant melanoma is the most invasive and deadly form of skin cancer with no
      effective therapy to treat advanced disease, leading to poor survival rates. Akt3
      signaling plays an important role in deregulating apoptosis in approximately 70%
      of melanomas. Thus, targeting Akt3 signaling in melanoma patients has significant
      therapeutic potential for inhibiting melanomas, but no Akt3-specific
      chemotherapeutic agent exists. Unfortunately, nonspecific Akt inhibitors can
      cause systemic toxicity or increase metastasis. Identifying and targeting the
      Akt3 substrate that deregulates apoptosis might circumvent these complications
      but would require demonstration of its functional importance in disrupting normal
      apoptosis. In this study, PRAS40 was identified as an Akt3 substrate that
      deregulated apoptosis to promote melanoma tumorigenesis. Levels of phosphorylated
      PRAS40 (pPRAS40) increased during melanoma tumor progression paralleling
      increasing Akt3 activity. Majority of melanomas from patients with elevated Akt
      activity also had correspondingly higher levels of pPRAS40. Targeting PRAS40 or
      upstream Akt3 similarly reduced anchorage-independent growth in culture and
      inhibited tumor development in mice. Mechanistically, decreased pPRAS40 increased
      tumor cell apoptosis as well as sensitivity of melanoma cells to apoptosis
      inducing agents, thereby decreasing chemoresistance. Collectively, these studies
      provide a solid mechanistic basis for targeting PRAS40 to inhibit the Akt3
      signaling cascade and thereby retard melanoma development.

PMID- 17440075
TI  - SV40 oncoproteins enhance asbestos-induced DNA double-strand breaks and abrogate
      senescence in murine mesothelial cells.
AB  - SV40 virus has emerged as a potential cofactor with asbestos in the development
      of diffuse malignant mesothelioma, but its precise role in the pathogenesis of
      this tumor is unclear. SV40 large T antigen is known to inactivate cellular
      proteins involved in DNA damage and senescence, including p53 and pRb. We
      hypothesize that SV40 oncoproteins will sensitize mesothelial cells to DNA damage
      induced by asbestos or chemotherapeutic agents. SV40 oncoprotein expression in
      murine mesothelial cell lines enhanced spontaneous and asbestos-induced double
      strand breaks, indicated by gamma-H2AX foci, and potentiated micronucleus
      formation. Mesothelial cells exposed to asbestos or bleomycin for 96 h acquired
      senescent-like morphology and displayed elevated senescence-associated beta
      galactosidase activity, reduced bromodeoxyuridine (BrdUrd) incorporation, and
      reduced colony formation. SV40 oncoprotein expression abrogated the senescent
      phenotype, and transfected cell lines showed an increase in both BrdUrd
      incorporation and colony formation after prolonged DNA damage. Murine mesothelial
      cell lines lacking wild-type p53 due to a point mutation or gene rearrangement
      also failed to senesce in response to asbestos or chemotherapeutic agents. In
      addition, stress-induced senescence in human mesothelial cell lines was impaired
      by SV40 oncoprotein expression (MeT-5A), p53 small interfering RNA, or
      spontaneous p53 mutation (REN). These studies suggest that exposure to DNA
      damaging agents can induce senescence in both murine and human mesothelioma cell
      lines and suggest a major, although not exclusive, role for p53 in this response.
      SV40 virus may contribute to mesothelioma progression by impairing stress-induced
      senescence, in part through p53 inactivation, thereby favoring survival and
      proliferation of mesothelial cells that have sustained DNA damage.

PMID- 17440076
TI  - Monocyte chemotactic protein-1 mediates prostate cancer-induced bone resorption.
AB  - Prostate cancer preferentially metastasizes to bone, resulting in high mortality.
      Strategies to inhibit prostate cancer metastasis include targeting both tumor
      induced osteoblastic lesions and underlying osteoclastic activities. We and
      others have previously shown that blocking receptor activator of nuclear factor
      kappaB ligand (RANKL) partially blocks tumor establishment and progression in
      bone in murine models. However, levels of RANKL in the cell lines used in these
      studies were very low, suggesting that soluble factors other than RANKL may
      mediate the cancer-induced osteoclast activity. To identify these factors, a
      human cytokine antibody array was used to measure cytokine expression in
      conditioned medium collected from primary prostate epithelial cells (PrEC),
      prostate cancer LNCaP and its derivative C4-2B, and PC3 cells. All prostate
      cancer cells produced high amounts of monocyte chemotactic protein-1 (MCP-1)
      compared with PrEC cells. Furthermore, levels of interleukin (IL)-6, IL-8,
      GROalpha, ENA-78, and CXCL-16 were higher in PC3 than LNCaP. These results were
      confirmed by ELISA. Finally, human bone marrow mononuclear cells (HBMC) were
      cultured with PC3 conditioned medium. Although both recombinant human MCP-1 and
      IL-8 directly stimulated HBMC differentiation into osteoclast-like cells, IL-8,
      but not MCP-1, induced bone resorption on dentin slices with 21 days of culture
      in the absence of RANKL. However, the conditioned medium-induced bone resorption
      was inhibited by MCP-1 neutralizing antibody and was further synergistically
      inhibited with IL-8 antibody, indicating that MCP-1, in addition to IL-8,
      mediates tumor-induced osteoclastogenesis and bone resorption. MCP-1 may promote
      preosteoclast cell fusion, forming multinucleated tartrate-resistant acid
      phosphatase-positive osteoclast-like cells. This study may provide novel
      therapeutic targets for treatment of prostate cancer skeletal metastasis.

PMID- 17440077
TI  - Overexpressed cyclophilin A in cancer cells renders resistance to hypoxia- and
      cisplatin-induced cell death.
AB  - Cyclophilin A (CypA) has been reported to be overexpressed in cancer cells,
      especially in solid tumors. To determine the role of CypA in tumorigenesis, we
      investigated the induction of CypA as well as the role it plays in cancer cells.
      Here, we have shown that induction of CypA is associated with hypoxia in a
      variety of cells, including DU145 human prostate cancer cell line. Our analysis
      of the CypA promoter clearly showed that CypA up-regulation is mediated by
      hypoxia-inducible factor-1alpha transcription factor. Interestingly,
      overexpression of CypA prevented hypoxia- and cisplatin-induced apoptosis, and
      this was associated with the suppression of reactive oxygen species generation
      and depolarization of mitochondrial membrane potential, whereas small interfering
      RNA-based CypA knockdown aggravated these factors. These results suggest that
      CypA is important in tumorigenesis, especially in tumor apoptosis.

PMID- 17440078
TI  - Androgen-independent growth and tumorigenesis of prostate cancer cells are
      enhanced by the presence of PKA-differentiated neuroendocrine cells.
AB  - The neuroendocrine status of prostatic adenocarcinomas is considered a prognostic
      indicator for development of aggressive, androgen-independent disease.
      Neuroendocrine-like cells are thought to function by providing growth and
      survival signals to surrounding tumor cells, particularly following androgen
      ablation therapy. To test this hypothesis directly, LNCaP cells were engineered
      to inducibly express a constitutively activated form of the cyclic AMP-dependent
      protein kinase A catalytic subunit (caPKA), which was previously found upon
      transient transfection to be sufficient for acquisition of neuroendocrine-like
      characteristics and loss of mitotic activity. Clonal cells that inducibly
      expressed caPKA enhanced the growth of prostate tumor cells in anchorage
      dependent and anchorage-independent in vitro assays as well as the growth of
      prostate tumor xenografts in vivo, with the greatest effects seen under
      conditions of androgen deprivation. These results suggest that neuroendocrine
      like cells of prostatic tumors have the potential to enhance androgen-independent
      tumor growth in a paracrine manner, thereby contributing to progression of the
      disease.

PMID- 17440079
TI  - Transforming growth factor beta signaling via Ras in mesenchymal cells requires
      p21-activated kinase 2 for extracellular signal-regulated kinase-dependent
      transcriptional responses.
AB  - Transforming growth factor beta (TGF-beta) signaling via Smad proteins occurs in
      various cell types. However, whereas the biological response to TGF-beta can be
      as distinct as growth promoting (i.e., mesenchymal cells) versus growth
      inhibiting (i.e., epithelial cells), few discernible differences in TGF-beta
      signaling have been reported. In the current study, we examined the role of Ras
      in the proliferative response to TGF-beta and how it might interface with Smad
      dependent and Smad-independent TGF-beta signaling targets. TGF-beta stimulated
      Ras activity in a subset of mesenchymal, but not epithelial, cultures and was
      required for extracellular signal-regulated kinase (ERK)-dependent
      transcriptional responses. Although dominant negative Ras had no effect on TGF
      beta internalization or Smad-dependent signaling (i.e., phosphorylation, nuclear
      translocation, or SBE-luciferase activity), it did prevent the
      hyperphosphorylation of the Smad transcriptional corepressor TG-interacting
      factor (TGIF). This was not sufficient, however, to overcome the mitogenic
      response stimulated by TGF-beta, which was dependent on signals downstream of p21
      activated kinase 2 (PAK2). Moreover, although the initial activation of Ras and
      PAK2 are distinctly regulated, TGF-beta-stimulated PAK2 activity is required for
      Ras-dependent ERK phosphorylation and Elk-1 transcription. These findings show
      the requirement for crosstalk between two Smad-independent pathways in regulating
      TGF-beta proliferation and indicate that the mechanism(s) by which TGF-beta
      stimulates growth is not simply the opposite of its growth inhibitory actions.

PMID- 17440080
TI  - Modulation of angiogenic phenotype alters tumorigenicity in rat ovarian
      epithelial cells.
AB  - Vascular endothelial growth factor (VEGF) expression correlates with microvessel
      density, stage, malignant ascites, metastasis, and survival in ovarian cancer. By
      transducing VEGF165 into a nontumorigenic rat ovarian surface epithelial cell
      line (ROSE199), we investigated the direct effect of an angiogenic phenotype on
      tumor development. The neu oncogene, which is overexpressed in >30% of ovarian
      cancers, was used in comparison. Neu-transfected ROSE199 cells showed phenotypic
      characteristics of transformation in vitro with an abundance of focus-forming
      units in monolayer cultures and anchorage-independent growth in soft agar. In
      contrast, VEGF-secreting ROSE199 cells (VR) retained normal morphology and in
      vitro growth characteristics (e.g., proliferation rate) compared with parental
      ROSE199 cells. Interestingly, injection of VR cells into athymic mice formed
      malignant ascites in 100% of the animals when injected into the peritoneum and
      developed vascularized tumors in 85% of the mice when injected s.c. Furthermore,
      blocking VEGF-mediated signaling by the Flk-1/KDR receptor kinase inhibitor
      SU5416 significantly inhibited the growth of VR tumors. To validate that the
      proangiogenic switch is responsible for tumor development, the angiogenic
      phenotype was balanced by the inducible coexpression of endostatin under the
      control of Tet-activated promoter. Coexpression of endostatin along with VEGF
      reversed the tumorigenic phenotype of VR cells. These studies show that
      alterations in the angiogenic characteristics of ovarian surface epithelium may
      play an important role in the etiology of ovarian cancer, and that inhibition of
      angiogenesis can be effective in the treatment of epithelial ovarian cancer.

PMID- 17440081
TI  - Most C6 cells are cancer stem cells: evidence from clonal and population
      analyses.
AB  - Cancer stem cells have been isolated from human gliomas and many other
      parenchymal tumors. It was previously assumed that many established malignant
      cell lines also contain a rare subpopulation of stem cells. This study was
      designed to investigate the fraction of cancer stem cells in the C6 glioma cell
      line using clonal and population analyses, rather than isolating methods, which
      are based on specific markers. Interestingly, in the serum-containing medium,
      each of the 67 single C6 cells plated per miniwell was able to generate a clone
      and subclones, which subsequently gave rise to a xenograft glioma in the BALB/C
      nude mouse. The CD133- C6 cells also possessed clonogenic, self-renewal, and
      tumorigenic capacities. Moreover, our findings indicated that brief exposure to
      Hoechst 33342 was harmful to the clonogenicity and proliferation of individual C6
      cells. Therefore, the non-side-population cells may be deprived of their stem
      cell features in the process of Hoechst 33342 staining as a step in isolating a
      Hoechst-negative side population with flow cytometry. Thus, we concluded that the
      C6 line was mainly composed of cancer stem cells, although many of them were
      neither CD133+ nor side population.

PMID- 17440082
TI  - Synergistic effect of cyclin D1 and c-Myc leads to more aggressive and invasive
      mammary tumors in severe combined immunodeficient mice.
AB  - Cyclin D1 is one of the most commonly overexpressed oncogenes in breast cancer;
      yet, it is not clear whether cyclin D1 alone is capable of causing malignant
      transformation of mammary epithelial cells. Here, we show that ectopic expression
      of cyclin D1 in benign mouse mammary epithelial cells promotes cell
      proliferation, anchorage-independent growth in soft agar, and tumorigenesis in
      severe combined immunodeficient mice. To address the possible interaction of
      cyclin D1 and c-myc in malignant transformation, we used cyclin D1/c-myc dual
      expressing clones, which displayed more aggressive and invasive phenotype than
      cyclin D1-expressing clones. These data provide evidence that overexpression of
      cyclin D1 or coexpression with c-myc could cause invasive malignant
      transformation of benign mouse mammary epithelial cells. Furthermore, microarray
      analysis of cyclin D1 and cyclin D1/c-myc clones showed that these two tumor
      producing clones might use distinct invasive pathways. In summary, overexpression
      of cyclin D1 may commit mammary epithelia to a tumor-prone phenotype in which
      cooperation with other genes, such as synergy with c-myc, may lead to a more
      aggressive phenotype.

PMID- 17440083
TI  - Syndecan-2 affects the basal and chemotherapy-induced apoptosis in osteosarcoma.
AB  - Syndecans are transmembrane heparan sulfate proteoglycans controlling cell
      adhesion, migration, and proliferation. We previously showed that syndecan-2 is
      involved in the control of apoptosis in cultured osteosarcoma cells. These data
      led us to the hypothesis that syndecan-2 may play a role in the apoptotic
      signaling in bone tumors. We immunohistochemically analyzed tissue sections from
      biopsies from 21 patients with well-characterized osteosarcoma. These tissues
      expressed low levels of syndecan-2 compared with osteoblasts and osteocytes in
      normal bone. Cultured human osteosarcoma cells also produced lower mRNA levels of
      syndecan-2 than normal osteoblastic cells. Moreover, the presence of syndecan-2
      correlated with spontaneous apoptosis in osteosarcoma tissues as assessed by
      detection of DNA fragmentation in situ. Overexpression of syndecan-2 resulted in
      decreased number of migrating and invading U2OS osteosarcoma cells in Matrigel.
      In addition, overexpression of syndecan-2 sensitized human osteosarcoma cells to
      chemotherapy-induced apoptosis, increasing the response to methotrexate,
      doxorubicin, and cisplatin. Consistently, knockdown of the proteoglycan using
      stable transfection with a plasmid coding small interfering RNA resulted in
      inhibition of chemotherapy-induced apoptosis. Analysis of syndecan-2 expression
      both in biopsies and in corresponding postchemotherapy-resected tumors, as well
      as in cells treated with methotrexate or doxorubicin, showed that the cytotoxic
      action of chemotherapy can be associated with an increase in syndecan-2. These
      results provide support for a tumor-suppressor function for syndecan-2 and
      suggest that dysregulation of apoptosis may be related to abnormal syndecan-2
      expression or induction in osteosarcoma. Moreover, our data identify syndecan-2
      as a new factor mediating the antioncogenic effect of chemotherapeutic drugs.

PMID- 17440084
TI  - Identification of cancer stem cell-like side population cells in human
      nasopharyngeal carcinoma cell line.
AB  - Side population (SP) cells have been isolated from several solid tumors. They
      lack distinct molecular markers for cancer stem cells (CSC) and increasing
      evidence suggests that they may play an important role in tumorigenesis and
      cancer therapy. However, there are no reports about the existence and function of
      SP cells in nasopharyngeal carcinoma (NPC) cells thus far. In this study, we
      scanned SP cells from five NPC cell lines and investigated stem cell
      characteristics, such as proliferation, self-renewal, and differentiation, using
      SP cells from the widely-used CNE-2 NPC cell line. We observed a strong
      tumorigenesis ability of SP cells following in vivo transplantation into nonobese
      diabetic/severe combined immunodeficient mice. Immunofluorescence revealed that
      cytokine 19 was highly expressed on SP cells. SP cells were found to be more
      resistant to chemotherapy and radiotherapy and this was related to the ATP
      binding cassette half transporter member 2 of G family protein and Smoothened
      protein expression, respectively. Our results not only showed that SP cells in
      human NPC cell line CNE-2 had stem cell characteristics in vitro but also showed
      that they had a strong ability to form tumors in vivo. Importantly, we found the
      cell marker, cytokine 19, may serve as a potential molecular marker for further
      characterization of CSC. Taken together, our data shed light on tumorigenesis and
      therapeutic-resistant mechanisms, which are helpful for developing novel targets
      for effective clinical treatment of NPC.

PMID- 17440085
TI  - Resilience to transformation and inherent genetic and functional stability of
      adult neural stem cells ex vivo.
AB  - Recent observations have suggested that extensive culturing of adult neural stem
      cells (ANSCs) by exploiting the NeuroSphere assay might select for aggressive
      cell clones, endowed with neoplastic potential, that overgrow the rest of the
      native stem cells. However, a detailed study of the propensity of ANSCs to
      transform has never been thoroughly undertaken. Here, we report the first
      demonstration that ANSCs can be propagated in vitro for over a year, maintaining
      a strikingly stable profile with regard to self-renewal, differentiation, growth
      factor dependence, karyotype, and molecular profiling. Most importantly, the long
      term culturing of ANSCs did not result in the formation of tumors in vivo, even
      when ANSCs were transduced with Myc and Ras oncogenes. The cancer resistance
      could depend on specific mechanisms aimed at protecting ANSCs and preserved by
      optimal nonstressful culture conditions. In conclusion, besides a plentiful and
      safe source of cells for therapeutic applications, ANSCs provide an ideal model
      to study aging and cancer in the context of stemness.

PMID- 17440086
TI  - GRP78/BiP inhibits endoplasmic reticulum BIK and protects human breast cancer
      cells against estrogen starvation-induced apoptosis.
AB  - The recent development of hormonal therapy that blocks estrogen synthesis
      represents a major advance in the treatment of estrogen receptor-positive breast
      cancer. However, cancer cells often acquire adaptations resulting in resistance.
      A recent report reveals that estrogen starvation-induced apoptosis of breast
      cancer cells requires BIK, an apoptotic BH3-only protein located primarily at the
      endoplasmic reticulum (ER). Searching for novel partners that interact with BIK
      at the ER, we discovered that BIK selectively forms complex with the glucose
      regulated protein GRP78/BiP, a major ER chaperone with prosurvival properties
      naturally induced in the tumor microenvironment. GRP78 overexpression decreases
      apoptosis of 293T cells induced by ER-targeted BIK. For estrogen-dependent MCF
      7/BUS breast cancer cells, overexpression of GRP78 inhibits estrogen starvation
      induced BAX activation, mitochondrial permeability transition, and consequent
      apoptosis. Further, knockdown of endogenous GRP78 by small interfering RNA
      (siRNA) sensitizes MCF-7/BUS cells to estrogen starvation-induced apoptosis. This
      effect was substantially reduced when the expression of BIK was also reduced by
      siRNA. Our results provide the first evidence that GRP78 confers resistance to
      estrogen starvation-induced apoptosis in human breast cancer cells via a novel
      mechanism mediated by BIK. These results further suggest that GRP78 expression
      level in the tumor cells may serve as a prognostic marker for responsiveness to
      hormonal therapy based on estrogen starvation and that combination therapy
      targeting GRP78 may enhance efficacy and reduce resistance.

PMID- 17440087
TI  - Acidic triterpenes compromise growth and survival of astrocytoma cell lines by
      regulating reactive oxygen species accumulation.
AB  - Several studies have shown how pentacyclic triterpenes can inhibit proliferation
      and induce apoptosis of some tumor cell lines; however, its effect on astrocytic
      tumors, one of the most malignant forms of cancer, has rarely been reported. The
      aim of this study was to examine how the pentacyclic triterpenes, oleanolic acid
      and maslinic acid, isolated from olive juice, affected astrocytoma cell
      morphology and survival. Cell proliferation was inhibited in 1321N1 astrocytoma
      cells by using 1 to 50 micromol/L of either oleanolic acid or maslinic acid, with
      an average IC(50) of 25 micromol/L. Growth inhibition led to morphologic and
      cytoskeletal alterations associated with the loss of stellate morphology and
      characterized by a retraction of the cytoplasm and collapse of actin stress
      fibers. Using 4',6-diamidino-2-phenylindole and Annexin V, we showed that
      astrocytoma cell death induced by oleanolic acid or maslinic acid were mainly due
      to apoptotic events. Furthermore, we showed that caspase-3 is activated as a
      consequence of triterpene treatment. Finally, we found that exposure of the cells
      to oleanolic acid or maslinic acid resulted in a significant increase of
      intracellular reactive oxygen species, followed by loss of mitochondrial membrane
      integrity. Importantly, enzymatic scavengers, such as catalase, or phenolic
      antioxidants, such as butylated hydroxytoluene, rescued cells from the triterpene
      mediated apoptosis, suggesting that the potential therapeutic effect of these
      acidic triterpenes is dependent on oxidative stress. Our data show that acidic
      triterpenes play a major role in 1321N1 astrocytoma morphology and viability and
      support the conclusion that oleanolic acid and maslinic acid may thus be
      promising new agents in the management of astrocytomas.

PMID- 17440088
TI  - Src phosphorylates Tyr284 in TGF-beta type II receptor and regulates TGF-beta
      stimulation of p38 MAPK during breast cancer cell proliferation and invasion.
AB  - Genetic and epigenetic events often negate the cytostatic function of
      transforming growth factor-beta (TGF-beta) in mammary epithelial cells (MEC),
      which ultimately enables malignant MECs to proliferate, invade, and metastasize
      when stimulated by TGF-beta. The molecular mechanisms underlying this phenotypic
      conversion of TGF-beta function during mammary tumorigenesis remain poorly
      defined. We previously established alpha(v)beta(3) integrin and Src as essential
      mediators of mitogen-activated protein kinase (MAPK) activation, invasion, and
      epithelial-to-mesenchymal transition stimulated by TGF-beta in normal and
      malignant MECs. Mechanistically, beta(3) integrin interacted physically with the
      TGF-beta type II receptor (TbetaR-II), leading to its tyrosine phosphorylation by
      Src and the initiation of oncogenic signaling by TGF-beta. We now show herein
      that Src phosphorylated TbetaR-II on Y284 both in vitro and in vivo.
      Interestingly, although the expression of Y284F-TbetaR-II mutants in breast
      cancer cells had no effect on TGF-beta stimulation of Smad2/3, this TbetaR-II
      mutant completely abrogated p38 MAPK activation by TGF-beta. Accordingly, Src
      mediated phosphorylation of Y284 coordinated the docking of the SH2 domains of
      growth factor receptor binding protein 2 (Grb2) and Src homology domain 2
      containing (Shc) TbetaR-II, thereby associating these adapter proteins to MAPK
      activation by TGF-beta. Importantly, Y284F-TbetaR-II mutants also abrogated
      breast cancer cell invasion induced by alpha(v)beta(3) integrin and TGF-beta as
      well as partially restored their cytostatic response to TGF-beta. Our findings
      have identified a novel alpha(v)beta(3) integrin/Src/Y284/TbetaR-II signaling
      axis that promotes oncogenic signaling by TGF-beta in malignant MECs and suggest
      that antagonizing this signaling axis may one day prove beneficial in treating
      patients with metastatic breast cancers.

PMID- 17440089
TI  - Molecular mechanisms underlying FIP1L1-PDGFRA-mediated myeloproliferation.
AB  - An interstitial deletion on chromosome 4q12 resulting in the formation of the
      FIP1L1-PDGFRA fusion protein is involved in the pathogenesis of imatinib
      sensitive chronic eosinophilic leukemia. The molecular mechanisms underlying the
      development of disease are largely undefined. Human CD34(+) hematopoietic
      progenitor cells were used to investigate the role of FIP1L1-PDGFRA in modulating
      lineage development. FIP1L1-PDGFRA induced both proliferation and differentiation
      of eosinophils, neutrophils, and erythrocytes in the absence of cytokines, which
      could be inhibited by imatinib. Whereas expression of FIP1L1-PDGFRA in
      hematopoietic stem cells and common myeloid progenitors induced the formation of
      multiple myeloid lineages, expression in granulocyte-macrophage progenitors
      induced only the development of eosinophils, neutrophils, and myeloblasts.
      Deletion of amino acids 30 to 233 in the FIP1L1 gene [FIP1L1(1-29)-PDGFRA] gave
      rise to an intermediate phenotype, exhibiting a dramatic reduction in the number
      of erythrocytes. FIP1L1-PDGFRA and FIP1L1(1-29)-PDGFRA both induced the
      activation of p38 and extracellular signal-regulated kinase 1/2 (ERK1/2) in
      myeloid progenitors, whereas signal transducers and activators of transcription 5
      (STAT5) and protein kinase B/c-akt were only activated by FIP1L1-PDGFRA. Dominant
      negative STAT5 partially inhibited FIP1L1-PDGFRA-induced colony formation,
      whereas combined inhibition of phosphatidylinositol-3-kinase and ERK1/2
      significantly reversed FIP1L1-PDGFRA-induced colony formation. Taken together,
      these results suggest that expression of FIP1L1-PDFGRA in human hematopoietic
      progenitors induce a myeloproliferative phenotype via activation of multiple
      signaling molecules including phosphatidylinositol-3-kinase, ERK1/2, and STAT5.

PMID- 17440090
TI  - Mechanism of action of the microtubule-targeted antimitotic depsipeptide
      tasidotin (formerly ILX651) and its major metabolite tasidotin C-carboxylate.
AB  - Tasidotin (ILX-651), an orally active synthetic microtubule-targeted derivative
      of the marine depsipeptide dolastatin-15, is currently undergoing clinical
      evaluation for cancer treatment. Tasidotin inhibited proliferation of MCF7/GFP
      breast cancer cells with an IC(50) of 63 nmol/L and inhibited mitosis with an
      IC(50) of 72 nmol/L in the absence of detectable effects on spindle microtubule
      polymer mass. Tasidotin inhibited the polymerization of purified tubulin into
      microtubules weakly (IC(50) approximately 30 micromol/L). However, it strongly
      suppressed the dynamic instability behavior of the microtubules at their plus
      ends at concentrations approximately 5 to 10 times below those required to
      inhibit polymerization. Its major actions were to reduce the shortening rate, the
      switching frequency from growth to shortening (catastrophe frequency), and the
      fraction of time the microtubules grew. In contrast with all other microtubule
      targeted drugs thus far examined that can inhibit polymerization, tasidotin did
      not inhibit the growth rate. In contrast to stabilizing plus ends, tasidotin
      enhanced microtubule dynamic instability at minus ends, increasing the shortening
      length, the fraction of time the microtubules shortened, and the catastrophe
      frequency and reducing the rescue frequency. Tasidotin C-carboxylate, the major
      intracellular metabolite of tasidotin, altered dynamic instability of purified
      microtubules in a qualitatively similar manner to tasidotin but was 10 to 30
      times more potent. The results suggest that the principal mechanism by which
      tasidotin inhibits cell proliferation is by suppressing spindle microtubule
      dynamics. Tasidotin may be a relatively weak prodrug for the functionally active
      tasidotin C-carboxylate.

PMID- 17440091
TI  - Proteomic analysis of waldenstrom macroglobulinemia.
AB  - To better understand the molecular changes that occur in Waldenstrom
      macroglobulinemia (WM), we employed antibody-based protein microarrays to compare
      patterns of protein expression between untreated WM and normal bone marrow
      controls. Protein expression was defined as a >2-fold or 1.3-fold change in at
      least 67% of the tumor samples. Proteins up-regulated by >2-fold included Ras
      family proteins, such as Rab-4 and p62DOK, and Rho family proteins, such as
      CDC42GAP and ROKalpha. Other proteins up-regulated by >1.3-fold included cyclin
      dependent kinases, apoptosis regulators, and histone deacetylases (HDAC). We then
      compared the samples of patients with symptomatic and asymptomatic WM and showed
      similar protein expression signatures, indicating that the dysregulation of
      signaling pathways occurs early in the disease course. Three proteins were
      different by >2-fold in symptomatic versus asymptomatic, including the heat shock
      protein HSP90. Elevated protein expression was confirmed by immunohistochemistry
      and immunoblotting. Functional significance was validated by the induction of
      apoptosis and inhibition of proliferation using specific HDAC and HSP90
      inhibitors. This study, therefore, identifies, for the first time, multiple novel
      proteins that are dysregulated in WM, which both enhance our understanding of
      disease pathogenesis and represent targets of novel therapeutics.

PMID- 17440092
TI  - Interleukin-12 deficiency is permissive for angiogenesis in UV radiation-induced
      skin tumors.
AB  - We have shown previously that endogenous deficiency of interleukin (IL)-12
      promotes photocarcinogenesis in mice. To characterize the role of IL-12
      deficiency in tumor angiogenesis, we developed IL-12p35 knockout (IL-12 KO) mice
      on a C3H/HeN background. IL-12 KO mice and their wild-type (WT) counterparts were
      subjected to a photocarcinogenesis protocol. When tumor yield was stabilized,
      samples of tumor and tumor-uninvolved UVB-exposed skin were collected and
      subjected to immunohistochemistry, gelatinolytic zymography, real-time PCR, and
      Western blot analysis of angiogenic factors. We found that the protein, mRNA
      expression and/or activity of the matrix metalloproteinases (MMP)-2, MMP-3, MMP
      7, and MMP-9, and basic fibroblast growth factor, which play crucial roles in
      tumor growth, were significantly higher in UVB-exposed skin and tumors of IL-12
      KO mice compared with WT mice. With respect to the tumor vasculature, the
      expression of CD31-positive cells and the expression of vascular endothelial
      growth factor were higher in the tumors of IL-12 KO mice than WTs. The
      proliferative capacity of tumor cells of the IL-12 KO mice was significantly
      higher than their WT counterparts when determined by 3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide assay and by analyzing the expression of cyclin
      D1. The level of the proinflammatory cytokine IL-6 and the expression of IL-23 in
      tumors of IL-12 KO mice were markedly higher than in the tumors of WT mice. IL-23
      has been shown to promote tumor growth. Together, these data indicate for the
      first time that IL-12 deficiency promotes proangiogenic stimuli in UVB-induced
      skin tumors and suggest that endogenous enhancement of IL-12 levels may be
      effective in the prevention and treatment of UV-induced skin cancers.

PMID- 17440093
TI  - Therapeutic effect of rapamycin on gallbladder cancer in a transgenic mouse
      model.
AB  - The macrolide fungicide rapamycin has shown significant antiproliferative action
      toward a variety of tumor types. In this study, we used BK5.erbB2 transgenic mice
      as an animal model to examine the therapeutic effect of rapamycin as a potential
      treatment for gallbladder cancer. Homozygous BK5.erbB2 mice overexpressing the
      wild-type rat erbB2 gene in basal epithelial cells of the gallbladder have an
      approximately 70% incidence of gallbladder adenocarcinoma by 2 to 3 months of
      age. Groups of mice ( approximately 2-3 months of age) were treated with
      rapamycin by i.p. injection (once daily for 14 days) and then sacrificed 24 h
      after the last treatment. Rapamycin significantly reduced the incidence and
      severity of gallbladder carcinoma in BK5.erbB2 mice in a dose-dependent manner.
      Tumors responsive to treatment exhibited a higher number of apoptotic cells.
      Furthermore, rapamycin treatment led to decreased levels of phosphorylated p70 S6
      kinase (Thr(389)) in gallbladder tissue as assessed by both Western blot and
      immunofluorescence analyses. Finally, immunofluorescence staining revealed
      elevated phosphorylated Akt (Ser(473)) and phosphorylated mammalian target of
      rapamycin (mTOR; Ser(2448)) in human gallbladder cancer compared with normal
      gallbladder tissue. Based on our results using a novel genetically engineered
      mouse model and the fact that the Akt/mTOR pathway is activated in human
      gallbladder cancer, rapamycin and related drugs may be effective therapeutic
      agents for the treatment of human gallbladder cancer.

PMID- 17440094
TI  - Celecoxib toxicity is cell cycle phase specific.
AB  - Celecoxib inhibits proliferation and induces apoptosis in human tumors, but the
      molecular mechanisms for these processes are poorly understood. In this study, we
      evaluated the ability of celecoxib to induce toxicity in head and neck squamous
      cell carcinomas (HNSCC) and explored the relationships between celecoxib-induced
      cell cycle inhibition and toxicity in HNSCC. Celecoxib inhibited the
      proliferation of UM-SCC-1 and UM-SCC-17B cells both in vitro and in vivo,
      accompanied by G(1) phase cell cycle arrest and apoptosis. Celecoxib induced
      p21(waf1/cip1) at the transcriptional level independent of wild-type p53
      function, leading to decreased expression of cyclin D1 and hypophosphorylation of
      Rb, with subsequent marked downstream decreases in nuclear E2F-1 protein
      expression and E2F transactivating activity by luciferase reporter assay. Cell
      cycle phase-specific cytometric sorting showed that celecoxib induced clonogenic
      toxicity preferentially to cells within the S phase greater than G(1) and G(2)
      phases. Levels of p21(waf1/cip1) and cyclin D1 protein were reduced in the S
      phase compared with the G(1) and G(2) phases, suggesting a possible protective
      role for p21(waf1/cip1) expression in celecoxib toxicity. In conclusion, we show
      that celecoxib has marked antiproliferative activity against head and neck cancer
      cells through transcriptional induction of p21(waf1/cip1) and G(1) phase
      accumulation leading to S phase-specific clonogenic toxicity. We additionally
      show that a profound inhibition of nuclear E2F function provides a possible
      mechanism for this S phase-specific toxicity.

PMID- 17440095
TI  - Activatable fluorescent molecular imaging of peritoneal metastases following
      pretargeting with a biotinylated monoclonal antibody.
AB  - Optical probes that yield high target-to-background ratios are necessary to
      detect microfoci of cancer that would otherwise escape detection with white light
      imaging. Target-specific activation of the optical signal at tumor foci is one
      mechanism by which high target and low background signal can be achieved. Here,
      we describe a two-step activation process in which the tumors are first
      pretargeted with a nonfluorescent biotinylated monoclonal antibody [cetuximab
      (Erbitux) targeting human epidermal growth factor receptor type 1 (HER1)].
      Following this, a second agent, neutravidin-BODIPY-FL fluorescent conjugate, is
      given and binds to the previously targeted antibody, resulting in an
      approximately 10-fold amplification of the optical fluorescence signal, leading
      to high tumor-to-background ratios. Spectral fluorescence imaging was done in a
      mouse model of peritoneal metastasis using a HER1-overexpressing cell line (A431)
      after pretargeting with biotinylated cetuximab and 3 h after administration of
      neutravidin-conjugated BODIPY-FL. Both aggregated tumors as well as small cancer
      implants were clearly visualized in vivo. For lesions approximately 0.8 mm or
      greater in diameter, the spectral fluorescence imaging had a sensitivity of 96%
      (178 of 185) and a specificity of 98% (188 of 191). This two-step activation
      paradigm (pretargeting followed by neutravidin-biotin binding with an attached
      activatable fluorophore) could be useful in tumor-specific molecular imaging of
      various targets to guide surgical resections.

PMID- 17440096
TI  - In vitro and in vivo molecular evidence for better therapeutic efficacy of ABT
      627 and taxotere combination in prostate cancer.
AB  - Bone is the key metastatic site for prostate cancer. Endothelin 1 (ET-1) produced
      abundantly by prostate cancer cells binds to its receptor present on bone marrow
      stromal cells and favors osteoblastic response during bone metastases of prostate
      cancer. This suggests that interrupting ET-1 interaction with its endothelin A
      (ET(A)) receptor could be useful for inhibiting prostate cancer bone metastasis
      and, as such, may enhance the therapeutic activity of docetaxel (Taxotere), the
      most commonly used drug for the treatment of metastatic prostate cancer.
      Therefore, the goal of our study was to obtain preclinical data supporting our
      hypothesis that the combined use of ET(A) receptor antagonist (ABT-627;
      Atrasentan) with Taxotere will be superior in inducing apoptosis in vitro and
      inhibiting tumor growth in vivo in a SCID-hu model of experimental bone
      metastasis induced by C4-2b prostate cancer cells. In vitro studies were done on
      a panel of prostate cancer cell lines to understand the molecular basis of
      combination therapy, and we found that the combination was more effective in the
      inhibition of cell viability and induction of apoptosis in LNCaP and C4-2b cells
      (androgen receptor positive) but not in PC-3 cells. These results were correlated
      with inactivation of Akt/nuclear factor-kappaB and its target genes. For in vivo
      studies, the therapeutic regimen was initiated when the tumor began showing signs
      of growth and treatment was continued for 5 weeks. Tumor volume and serum
      prostate-specific antigen were used as terminal index to evaluate the therapeutic
      advantage of combination therapy relative to a single regimen and untreated
      control. At termination, we found a 90% reduction in tumor volume by combination
      treatment relative to the untreated control group. Most importantly, the
      antitumor activity was associated with the down-regulation of molecular markers
      in tumor tissues that were similar to those observed in vitro.

PMID- 17440097
TI  - Tumor necrosis factor receptor 1/c-Jun-NH2-kinase signaling promotes human
      neoplasia.
AB  - The tumor necrosis factor alpha receptor (TNFR1) activates downstream effectors
      that include the mitogen-activated protein kinase kinase 7 (MKK7)/c-Jun-NH(2)
      kinase (JNK)/activator protein 1 (AP1) cascade. Here, we report that JNK is
      activated in a majority of spontaneous human squamous cell carcinomas (SCC). JNK
      pathway induction bypassed cell cycle restraints induced by oncogenic Ras and
      cooperated with Ras to convert normal human epidermis into tumors
      indistinguishable from SCC, confirming its oncogenic potency in human tissue.
      Inhibiting MKK7, JNK, and AP1 as well as TNFR1 itself using genetic,
      pharmacologic, or antibody-mediated approaches abolished invasive human epidermal
      neoplasia in a tumor cell autonomous fashion. The TNFR1/MKK7/JNK/AP1 cascade thus
      promotes human neoplasia and represents a potential therapeutic target for human
      epithelial cancers.

PMID- 17440098
TI  - Systemic overexpression of angiopoietin-2 promotes tumor microvessel regression
      and inhibits angiogenesis and tumor growth.
AB  - Angiopoietin-2 (Ang-2) is a conditional antagonist and agonist for the
      endothelium-specific Tie-2 receptor. Although endogenous Ang-2 cooperates with
      vascular endothelial growth factor (VEGF) to protect tumor endothelial cells, the
      effect on tumor vasculature of high levels of exogenous Ang-2 with different
      levels of VEGF has not been studied in detail. Here, we report that systemic
      overexpression of Ang-2 leads to unexpected massive tumor vessel regression
      within 24 h, even without concomitant inhibition of VEGF. By impairing pericyte
      coverage of the tumor vasculature, Ang-2 destabilizes the tumor vascular bed
      while improving perfusion in surviving tumor vessels. Ang-2 overexpression
      transiently exacerbates tumor hypoxia without affecting ATP levels. Although
      sustained systemic Ang-2 overexpression does not affect tumor hypoxia and
      proliferation, it significantly inhibits tumor angiogenesis, promotes tumor
      apoptosis, and suppresses tumor growth. The similar antitumoral, antiangiogenic
      efficacy of systemic overexpression of Ang-2, soluble VEGF receptor-1, and the
      combination of both suggests that concomitant VEGF inhibition is not required for
      Ang-2-induced tumor vessel regression and growth delay. This study shows the
      important roles of Ang-2-induced pericyte dropout during tumor vessel regression.
      It also reveals that elevated Ang-2 levels have profound pleiotropic effects on
      tumor vessel structure, perfusion, oxygenation, and apoptosis.

PMID- 17440099
TI  - Gene expression profiling of breast, prostate, and glioma cells following single
      versus fractionated doses of radiation.
AB  - Studies were conducted to determine whether gene expression profiles following a
      single dose of radiation would yield equivalent profiles following fractionated
      radiation in different tumor cell lines. MCF7 (breast), DU145 (prostate), and
      SF539 (gliosarcoma) cells were exposed to a total radiation dose of 10 Gy
      administered as a single dose (SD) or by daily multifractions (MF) of 5 x 2 Gy.
      Following radiation treatment, mRNA was isolated at 1, 4, 10, and 24 h and
      processed for cDNA microarray analysis. To determine the influence of the tumor
      microenvironment on gene expression, one cell type (DU145) was evaluated growing
      as a solid tumor in athymic nude mice for both radiation protocols. Unsupervised
      hierarchical cluster map analysis showed significant differences in gene
      expression profiles between SD and MF treatments for cells treated in vitro, with
      MF yielding a more robust induction compared with SD. Several genes were uniquely
      up-regulated by MF treatment, including multiple IFN-related genes (STAT1, G1P2,
      OAS1, OAS3, G1P3, IFITM1) and TGF-beta-associated genes (EGR1, VEGF, THBS1, and
      TGFB2). DU145 cells grown in vivo exhibited a completely different set of genes
      induced by both SD and MF compared with the same cells exposed in vitro. The
      results of the study clearly show distinct differences in the molecular response
      of cells between SD and MF radiation exposures and show that the tumor
      microenvironment can significantly influence the pattern of gene expression after
      radiation exposures.

PMID- 17440100
TI  - Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of
      pancreatic cancer through suppression of proliferation, angiogenesis, and
      inhibition of nuclear factor-kappaB-regulated gene products.
AB  - Gemcitabine is currently the best treatment available for pancreatic cancer, but
      the disease develops resistance to the drug over time. Agents that can either
      enhance the effects of gemcitabine or overcome chemoresistance to the drug are
      needed for the treatment of pancreatic cancer. Curcumin, a component of turmeric
      (Curcuma longa), is one such agent that has been shown to suppress the
      transcription factor nuclear factor-kappaB (NF-kappaB), which is implicated in
      proliferation, survival, angiogenesis, and chemoresistance. In this study, we
      investigated whether curcumin can sensitize pancreatic cancer to gemcitabine in
      vitro and in vivo. In vitro, curcumin inhibited the proliferation of various
      pancreatic cancer cell lines, potentiated the apoptosis induced by gemcitabine,
      and inhibited constitutive NF-kappaB activation in the cells. In vivo, tumors
      from nude mice injected with pancreatic cancer cells and treated with a
      combination of curcumin and gemcitabine showed significant reductions in volume
      (P = 0.008 versus control; P = 0.036 versus gemcitabine alone), Ki-67
      proliferation index (P = 0.030 versus control), NF-kappaB activation, and
      expression of NF-kappaB-regulated gene products (cyclin D1, c-myc, Bcl-2, Bcl-xL,
      cellular inhibitor of apoptosis protein-1, cyclooxygenase-2, matrix
      metalloproteinase, and vascular endothelial growth factor) compared with tumors
      from control mice treated with olive oil only. The combination treatment was also
      highly effective in suppressing angiogenesis as indicated by a decrease in
      CD31(+) microvessel density (P = 0.018 versus control). Overall, our results
      suggest that curcumin potentiates the antitumor effects of gemcitabine in
      pancreatic cancer by suppressing proliferation, angiogenesis, NF-kappaB, and NF
      kappaB-regulated gene products.

PMID- 17440102
TI  - Sulfasalazine suppresses drug resistance and invasiveness of lung adenocarcinoma
      cells expressing AXL.
AB  - Metastasis and drug resistance are the major causes of mortality in patients with
      non-small cell lung cancer (NSCLC). Several receptor tyrosine kinases (RTKs),
      including AXL, are involved in the progression of NSCLC. The AXL/MER/SKY
      subfamily is involved in cell adhesion, motility, angiogenesis, and signal
      transduction and may play a significant role in the invasiveness of cancer cells.
      Notably, no specific inhibitors of AXL have been described. A series of CL1
      sublines with progressive invasiveness established from a patient with NSCLC has
      been identified that positively correlates with AXL expression and resistance to
      chemotherapeutic drugs. The ectopic overexpression of AXL results in elevated
      cell invasiveness and drug resistance. Nuclear factor-kappaB (NF-kappaB)
      signaling activity is associated with AXL expression and may play an important
      role in the enhancement of invasiveness and doxorubicin resistance, as shown by
      using the NF-kappaB inhibitor, sulfasalazine, and IkappaB dominant-negative
      transfectants. In the current study, sulfasalazine exerted a synergistic
      anticancer effect with doxorubicin and suppressed cancer cell invasiveness in
      parallel in CL1 sublines and various AXL-expressing cancer cell lines.
      Phosphorylation of AXL and other RTKs (ErbB2 and epidermal growth factor
      receptor) was abolished by sulfasalazine within 15 min, suggesting that the
      inhibition of NF-kappaB and the kinase activity of RTKs are involved in the
      pharmacologic effects of sulfasalazine. Our study suggests that AXL is involved
      in NSCLC metastasis and drug resistance and may therefore provide a molecular
      basis for RTK-targeted therapy using sulfasalazine to enhance the efficacy of
      chemotherapy in NSCLC.

PMID- 17440101
TI  - p53 and p21 determine the sensitivity of noscapine-induced apoptosis in colon
      cancer cells.
AB  - We have previously discovered the naturally occurring antitussive alkaloid
      noscapine as a tubulin-binding agent that attenuates microtubule dynamics and
      arrests mammalian cells at mitosis via activation of the c-Jun NH(2)-terminal
      kinase pathway. It is well established that the p53 protein plays a crucial role
      in the control of tumor cell response to chemotherapeutic agents and DNA-damaging
      agents; however, the relationship between p53-driven genes and drug sensitivity
      remains controversial. In this study, we compared chemosensitivity, cell cycle
      distribution, and apoptosis on noscapine treatment in four cell lines derived
      from the colorectal carcinoma HCT116 cells: p53(+/+) (p53-wt), p53(-/-) (p53
      null), p21(-/-) (p21-null), and BAX(-/-) (BAX-null). Using these isogenic
      variants, we investigated the roles of p53, BAX, and p21 in the cellular response
      to treatment with noscapine. Our results show that noscapine treatment increases
      the expression of p53 over time in cells with wild-type p53 status. This increase
      in p53 is associated with an increased apoptotic BAX/Bcl-2 ratio consistent with
      increased sensitivity of these cells to apoptotic stimuli. Conversely, loss of
      p53 and p21 alleles had a counter effect on both BAX and Bcl-2 expression and the
      p53-null and p21-null cells were significantly resistant to the antiproliferative
      and apoptotic effects of noscapine. All but the p53-null cells displayed p53
      protein accumulation in a time-dependent manner on noscapine treatment.
      Interestingly, despite increased levels of p53, p21-null cells were resistant to
      apoptosis, suggesting a proapoptotic role of p21 and implying that p53 is a
      necessary but not sufficient condition for noscapine-mediated apoptosis.

PMID- 17440103
TI  - Sanguinarine-dependent induction of apoptosis in primary effusion lymphoma cells.
AB  - Primary effusion lymphoma (PEL) is an incurable, aggressive B-cell malignancy
      that develops rapid resistance to conventional chemotherapy. In efforts to
      identify novel approaches to block proliferation of PEL cells, we found that
      sanguinarine, a natural compound isolated from the root plant Sanguinaria
      canadendid, inhibits cell proliferation and induces apoptosis in a dose-dependent
      manner in several PEL cell lines. Our data show that sanguinarine treatment of
      PEL cells results in up-regulation of death receptor 5 (DR5) expression via
      generation of reactive oxygen species (ROS) and causes activation of caspase-8
      and truncation of Bid (tBid). Subsequently, tBid translocates to the mitochondria
      causing conformational changes in Bax, leading to loss of mitochondrial membrane
      potential and release of cytochrome c to the cytosol. Sanguinarine-induced
      release of cytochrome c results in activation of caspase-9 and caspase-3 and
      poly(ADP-ribose) polymerase (PARP) cleavage, leading to induction of caspase
      dependent apoptosis. In addition, we show that pretreatment of PEL cells with
      carbobenzoxy-Val-Ala-Asp-fluoromethylketone, a universal inhibitor of caspases,
      abrogates caspase and PARP activation and prevents cell death induced by
      sanguinarine. Moreover, treatment of PEL cells with sanguinarine down-regulates
      expression of inhibitor of apoptosis proteins (IAP). Finally, N-acetylcysteine,
      an inhibitor of ROS, inhibits sanguinarine-induced generation of ROS, up
      regulation of DR5, Bax conformational changes, activation of caspase-3, and down
      regulation of IAPs. Taken together, our findings suggest that sanguinarine is a
      potent inducer of apoptosis of PEL cells via up-regulation of DR5 and raise the
      possibility that this agent may be of value in the development of novel
      therapeutic approaches for the treatment of PEL.

PMID- 17440104
TI  - Enhanced antitumor activity of T cells engineered to express T-cell receptors
      with a second disulfide bond.
AB  - Adoptive transfer of genetically T-cell receptor (TCR)-modified lymphocytes has
      been recently reported to cause objective cancer regression. However, a major
      limitation to this approach is the mispairing of the introduced chains with the
      endogenous TCR subunits, which leads to reduced TCR surface expression and,
      subsequently, to their lower biological activity. We here show that it is
      possible to improve TCR gene transfer by adding a single cysteine on each
      receptor chain to promote the formation of an additional interchain disulfide
      bond. We show that cysteine-modified receptors were more highly expressed on the
      surface of human lymphocytes compared with their wild-type counterparts and able
      to mediate higher levels of cytokine secretion and specific lysis when cocultured
      with specific tumor cell lines. Furthermore, cysteine-modified receptors retained
      their enhanced function in CD4(+) lymphocytes. We also show that this approach
      can be employed to enhance the function of humanized and native murine receptors
      in human cells. Preferential pairing of cysteine-modified receptor chains
      accounts for these observations, which could have significant implications for
      the improvement of TCR gene therapy.

PMID- 17440105
TI  - Mechanistic influences for mutation induction curves after exposure to DNA
      reactive carcinogens.
AB  - A mechanistic understanding of carcinogenic genotoxicity is necessary to
      determine consequences of chemical exposure on human populations and improve
      health risk assessments. Currently, linear dose-responses are assumed for DNA
      reactive compounds, ignoring cytoprotective processes that may limit permanent
      damage. To investigate the biological significance of low-dose exposures, human
      lymphoblastoid cells were treated with alkylating agents that have different
      mechanisms of action and DNA targets: methylmethane sulfonate (MMS),
      methylnitrosourea (MNU), ethylmethane sulfonate (EMS), and ethylnitrosourea
      (ENU). Chromosomal damage and point mutations were quantified with the
      micronucleus and hypoxanthine phosphoribosyltransferase forward mutation assays.
      MNU and ENU showed linear dose-responses, whereas MMS and EMS had nonlinear
      curves containing a range of nonmutagenic low doses. The lowest observed effect
      level for induction of chromosomal aberrations was 0.85 microg/mL MMS and 1.40
      microg/mL EMS; point mutations required 1.25 microg/mL MMS and 1.40 microg/mL EMS
      before a mutagenic effect was detected. This nonlinearity could be due to
      homeostatic maintenance by DNA repair, which is efficient at low doses of
      compounds that primarily alkylate N(7)-G and rarely attack O atoms. A pragmatic
      threshold for carcinogenicity may therefore exist for such genotoxins.

PMID- 17440106
TI  - Degrasyn activates proteasomal-dependent degradation of c-Myc.
AB  - c-Myc is a highly unstable transcription factor whose deregulation and increased
      expression are associated with cancer. Degrasyn, a small synthetic molecule,
      induces rapid degradation of c-Myc protein in MM-1 multiple myeloma and other
      tumor cell lines. Destruction of c-Myc by degrasyn requires the presence of a
      region of c-Myc between amino acid residues 316 and 378 that has not previously
      been associated with c-Myc stability. Degrasyn-induced degradation of c-Myc
      depends on proteasomes but is independent of the degron regions previously shown
      to be important for ubiquitin-mediated targeting and proteasomal destruction of
      the protein. Degrasyn-dependent c-Myc proteolysis is not mediated by any
      previously identified c-Myc regulatory mechanism, does not require new protein
      synthesis, and does not depend on the nuclear localization of c-Myc. Degrasyn
      reduced c-Myc levels in A375 melanoma cells and in A375 tumors in nude mice, and
      this activity correlated with tumor growth inhibition. Together, these results
      suggest that degrasyn reduces the stability of c-Myc in vitro and in vivo through
      a unique signaling process that uses c-Myc domains not previously associated with
      c-Myc regulation.

PMID- 17440107
TI  - Expression of tumor-associated differentiation antigens, MUC1 glycoforms and CEA,
      in human thymic epithelial cells: implications for self-tolerance and tumor
      therapy.
AB  - Expression of tissue-restricted self-antigens in the thymus, termed promiscuous
      gene expression, imposes T cell tolerance and protects from autoimmune diseases.
      This antigen pool also includes various types of tumor-associated antigens (TAA)
      previously thought to be secluded from the immune system. The scope of
      promiscuous gene expression has been defined by mRNA analysis at the global level
      of isolated medullary thymic epithelial cells (mTECs). Information at the protein
      level on the frequency of mTECs expressing a given antigen, on coexpression
      patterns, and post-translational modifications is largely missing. We report here
      promiscuous expression at the protein level of two TAA, MUC1 and CEA, in situ and
      in purified human mTECs. Both antigens are expressed in 1% to 3% of mTECs, either
      individually or coexpressed in the same cell. Using a panel of anti-MUC1
      monoclonal antibodies recognizing different post-translational modifications,
      i.e., glycoforms of MUC1, we show that only fully glycosylated forms of MUC1 and
      the differentiation-dependent glycoforms were detected on mTECs, but not the
      cancer-associated glycoforms. Our findings imply that MUC1 and CEA are amenable
      to central tolerance induction, which might, however, be incomplete in case of
      tumor cell-restricted MUC1 glycoforms. Knowledge of these subtleties in
      promiscuous gene expression may, in the future, assist the selection of T cell
      tumor vaccines for clinical trials.

PMID- 17440108
TI  - Selective targeting and potent control of tumor growth using an EphA2/CD3
      Bispecific single-chain antibody construct.
AB  - The EphA2 receptor tyrosine kinase is frequently overexpressed and functionally
      altered in malignant cells and thus provides opportunities for selective
      targeting of tumor cells. We describe here the development of a novel, bispecific
      single-chain antibody (bscAb) referred to as bscEphA2xCD3. This molecule
      simultaneously targets EphA2 on tumor cells and the T-cell receptor/CD3 complex
      on T cells and possesses structural and functional characteristics of the
      recently developed BiTE technology. An EphA2-specific single-chain antibody was
      selected for recognition of an epitope that is preferentially exposed on
      malignant cells based on the concept of epitope exclusion; this was fused to a
      CD3-specific single-chain antibody to generate bscEphA2xCD3. The resultant bscAb
      redirected unstimulated human T cells to lyse EphA2-expressing tumor cells both
      in vitro and in vivo. In separate experiments, efficient tumor cell lysis was
      achieved in vitro at drug concentrations <or=1 microg/mL, at a low T-cell
      effector-to-tumor target cell ratio (1:1), and with tumor cells that possess few
      available binding sites (2,400 per cell) for bscEphA2xCD3. Time-lapsed microscopy
      revealed potent cytotoxic activity of bscEphA2xCD3-activated T cells against
      monolayers of malignant cells but not against monolayers of nontransformed EphA2
      positive cells except at the edges of the monolayer where the target epitope was
      exposed. BscEphA2xCD3 was also efficacious in human xenograft mouse models
      modified to show human T-cell killing of tumors. Together, our results reveal
      opportunities for redirecting the potent activity of cytotoxic T cells towards
      tumor cells that express selectively accessible epitopes and establish EphA2
      specific bscAb molecules as novel and potent therapeutics with selectivity for
      tumor cells.

PMID- 17440109
TI  - M3 muscarinic receptor antagonists inhibit small cell lung carcinoma growth and
      mitogen-activated protein kinase phosphorylation induced by acetylcholine
      secretion.
AB  - The importance of acetylcholine as a neurotransmitter in the nervous system is
      well established, but little is yet known about its recently described role as an
      autocrine and paracrine hormone in a wide variety of nonneuronal cells.
      Consistent with the expression of acetylcholine in normal lung, small cell lung
      carcinoma (SCLC) synthesize and secrete acetylcholine, which acts as an autocrine
      growth factor through both nicotinic and muscarinic cholinergic mechanisms. The
      purpose of this study was to determine if interruption of autocrine muscarinic
      cholinergic signaling has potential to inhibit SCLC growth. Muscarinic receptor
      (mAChR) agonists caused concentration-dependent increases in intracellular
      calcium and mitogen-activated protein kinase (MAPK) and Akt phosphorylation in
      SCLC cell lines. The inhibitory potency of mAChR subtype-selective antagonists
      and small interfering RNAs (siRNAs) on acetylcholine-increased intracellular
      calcium and MAPK and Akt phosphorylation was consistent with mediation by M3
      mAChR (M3R). Consistent with autocrine acetylcholine secretion stimulating MAPK
      and Akt phosphorylation, M3R antagonists and M3R siRNAs alone also caused a
      decrease in basal levels of MAPK and Akt phosphorylation in SCLC cell lines.
      Treatment of SCLC cells with M3R antagonists inhibited cell growth both in vitro
      and in vivo and also decreased MAPK phosphorylation in tumors in nude mice in
      vivo. Immunohistochemical staining of SCLC and additional cancer types showed
      frequent coexpression of acetylcholine and M3R. These findings suggest that M3R
      antagonists may be useful adjuvants for treatment of SCLC and, potentially, other
      cancers.

PMID- 17440110
TI  - Aromatase localization in human breast cancer tissues: possible interactions
      between intratumoral stromal and parenchymal cells.
AB  - Aromatase is a key enzyme in intratumoral estrogen production required for the
      production of estrogens through the conversion of serum androgens in
      postmenopausal breast cancer patients. There have been, however, controversies
      regarding the intratumoral localization of aromatase in human breast carcinoma
      tissues. Therefore, we have first examined the intratumoral localization of
      aromatase mRNA/protein in 19 breast carcinomas using laser capture
      microdissection/quantitative reverse transcription-PCR (RT-PCR) and
      immunohistochemistry. Aromatase mRNA and protein were detected in both
      intratumoral stromal and parenchymal cells in breast carcinoma tissues.
      Subsequent microarray expression profiling and clustering analyses, in addition
      to quantitative RT-PCR studies, showed a significant positive correlation between
      aromatase and estrogen-related receptor alpha mRNA expression in isolated
      carcinoma cells. We further examined an interaction between stromal cells
      isolated from human breast carcinoma tissues and breast carcinoma cell lines
      using a coculture system to study the biological characteristic of aromatase
      expression in carcinoma cells. Aromatase mRNA and enzyme activity and 17beta
      hydroxysteroid dehydrogenase type 1 mRNA in breast carcinoma cell lines,
      including MCF-7 and SK-BR-3 cells, were up-regulated in the presence of patient
      derived 32N or 74T intratumoral stromal cells. The results from steroid
      conversion assays were also consistent with the findings above. The results of
      our study also showed that aromatase inhibitors were more effective in inhibiting
      aromatization induced by coculture in MCF-7 than that in stromal 32N. The
      examination of the localization of aromatase and its regulation, including the
      interactions existing between different cell types in human breast carcinoma
      tissues, may provide important information as to achieving better clinical
      response to aromatase inhibitors in breast cancer patients.

PMID- 17440111
TI  - Estrogen receptor beta2 negatively regulates the transactivation of estrogen
      receptor alpha in human breast cancer cells.
AB  - Estrogens, by binding to and activating two estrogen receptors (ERalpha and
      ERbeta), are critically involved in the development of the mammary gland and
      breast cancer. An isoform of ERbeta, ERbeta2 (also called ERbetacx), with an
      altered COOH-terminal region, is coexpressed with ERalpha in many human breast
      cancers. In this study, we generated a stable cell line from MCF7 breast cancer
      cells expressing an inducible version of ERbeta2, along with endogenous ERalpha,
      and examined the effects of ERbeta2 on the ERalpha protein levels and function.
      We showed that ERbeta2 inhibited ERalpha-mediated transactivation via estrogen
      response element and activator protein-1 sites of reporter constructs as well as
      the endogenous genes pS2 and MMP-1. Chromatin immunoprecipitation assays revealed
      that ERbeta2 expression caused a significant reduction in the recruitment of
      ERalpha to both the pS2 and MMP-1 promoters. Furthermore, ERbeta2 expression
      induced proteasome-dependent degradation of ERalpha. The inhibitory effects of
      ERbeta2 on ERalpha activity were further confirmed in HEK293 cells that lack
      functional endogenous ERs. We also showed that ERbeta2 can interact with ERalpha
      both in vitro and in mammalian cells, which is compatible with a model where
      ERbeta2/ERalpha heterodimers are targeted to the proteasome. Finally, in human
      breast cancer samples, we observed that expression of ERbeta2 significantly
      correlated with ERalpha-negative phenotype. Our data suggest that ERbeta2 could
      influence ERalpha-mediated effects relevant for breast cancer development,
      including hormone responsiveness.

PMID- 17440112
TI  - Characterization of a germ-line deletion, including the entire INK4/ARF locus, in
      a melanoma-neural system tumor family: identification of ANRIL, an antisense
      noncoding RNA whose expression coclusters with ARF.
AB  - We have previously detected a large germ-line deletion, which included the entire
      p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster, in the largest melanoma-neural system
      tumor (NST) syndrome family known to date by means of heterozygosity mapping
      based on microsatellite markers. Here, we used gene dose mapping with sequence
      tagged site real-time PCR to locate the deletion end points, which were then
      precisely characterized by means of long-range PCR and nucleotide sequencing. The
      deletion was exactly 403,231 bp long and included the entire p15/CDKN2B,
      p16/CDKN2A, and p14/ARF genes. We then developed a simple and rapid assay to
      detect the junction fragment and to serve as a direct predictive DNA test for
      this large French family. We identified a new large antisense noncoding RNA
      (named ANRIL) within the 403-kb germ-line deletion, with a first exon located in
      the promoter of the p14/ARF gene and overlapping the two exons of p15/CDKN2B.
      Expression of ANRIL mainly coclustered with p14/ARF both in physiologic (various
      normal human tissues) and in pathologic conditions (human breast tumors). This
      study points to the existence of a new gene within the p15/CDKN2B-p16/CDKN2A
      p14/ARF locus putatively involved in melanoma-NST syndrome families and in
      melanoma-prone families with no identified p16/CDKN2A mutations as well as in
      somatic tumors.

PMID- 17440113
TI  - Specific growth rate versus doubling time for quantitative characterization of
      tumor growth rate.
AB  - Doubling time (DT) is widely used for quantification of tumor growth rate. DT is
      usually determined from two volume estimations with measurement time intervals
      comparable with or shorter than DT. Clinical data show that the frequency
      distribution of DT in patients is positively skewed, with some very long DT
      values compared with the average DT. Growth rate can also be quantified using
      specific growth rate (SGR; %/d), equal to ln2/DT. The aim of this work was to
      compare DT and SGR as growth rate variables. Growth rate calculations were
      computer simulated for a tumor with DT of 100 days, measurement time interval of
      1 to 200 days, and volume estimation uncertainty of 5% to 20%. Growth rate
      variables were determined and compared for previously published clinical data.
      The study showed that DT is not a suitable variable for tumor growth rate because
      (a) for short measurement time intervals, or high volume uncertainties, mean DT
      can either overestimate or underestimate the average growth rate; (b) DT is not
      defined if the consecutively estimated volumes are equal; and (c) the
      asymmetrical frequency distribution of DT makes it unsuitable for common
      statistical testing. In contrast, mean SGR and its equivalent DT give the correct
      values for average growth rate, SGR is defined for all tumor volume changes, and
      it has a symmetrical frequency distribution. SGR is also more accurate to use
      when discussing, for example, growth fraction, cell loss rate, and growth rate
      heterogeneities within the tumor. SGR should thus be used, instead of DT, to
      quantify tumor growth rate.

PMID- 17440114
TI  - Cyclooxygenase-2 transcription is regulated by human papillomavirus 16 E6 and E7
      oncoproteins: evidence of a corepressor/coactivator exchange.
AB  - Cyclooxygenase (COX-2) is overexpressed in human papillomavirus (HPV)-induced
      diseases, including cervical cancer. Although HPV E6 and E7 oncoproteins have
      been causally linked to cervical carcinogenesis, their effects on COX-2 gene
      expression are unknown. Increased levels of COX-2 mRNA, protein, and
      prostaglandin E(2) synthesis were detected in HPV16 E6- and E7-expressing
      cervical cancer cells (CaSki and SiHa) compared with an uninfected cervical
      cancer cell line (C33A). HPV16 E6 and E7 oncoproteins induced COX-2 transcription
      by activating the epidermal growth factor receptor (EGFR)-->Ras-->mitogen
      activated protein kinase pathway. Interestingly, HPV16 oncoproteins stimulated
      EGFR signaling, in part, by inducing the release of amphiregulin, an EGFR ligand.
      The inductive effects of HPV16 E6 and E7 were mediated by enhanced binding of
      activator protein-1 to the cyclic AMP (cAMP)-responsive element (-59/-53) of the
      COX-2 promoter. The potential contribution of coactivators and corepressors to
      HPV16 E6- and E7-mediated induction of COX-2 was also investigated. Chromatin
      immunoprecipitation assays indicated that E6 and E7 oncoproteins induced the
      recruitment of phosphorylated c-Jun, c-Fos, UbcH5, and cAMP-responsive element
      binding protein-binding protein/p300 to the COX-2 promoter. In contrast, E6 and
      E7 inhibited the binding of the histone deacetylase 3-nuclear receptor
      corepressor (NCoR) complex to the COX-2 promoter. Moreover, overexpression of
      NCoR blocked E6- and E7-mediated stimulation of the COX-2 promoter. Taken
      together, these results indicate that HPV16 E6 and E7 oncoproteins stimulated COX
      2 transcription by inducing a corepressor/coactivator exchange. To our knowledge,
      this study also provides the first evidence that NCoR can function as a repressor
      of COX-2 gene expression.

PMID- 17440115
TI  - Re: the terminology issue for myeloid-derived suppressor cells.

PMID- 17440116
TI  - Regulation of cytochrome P450 2E1 under hypertonic environment through TonEBP in
      human hepatocytes.
AB  - Whereas the liver as well as the other organs are continually exposed to the
      change of osmotic status, it has never been investigated whether activities and
      gene expressions of drug-metabolizing enzymes, including cytochromes P450, are
      dependent on osmotic change in the liver. In the present study, we determined
      that CYP2E1 is induced under hypertonic environments at a transcriptional level
      in human primary hepatocytes, as assessed by cDNA microarray and real time
      reverse transcription-polymerase chain reaction analyses. Both a protein level
      and the catalytic activity of CYP2E1 were consistently increased in response to
      hypertonic conditions. In promoter-reporter assay, it was demonstrated that -586
      to -566 in the CYP2E1 5'-flanking region was necessary for 2E1 promoter
      activation by hypertonic stimulation. It is noteworthy that tonicity-response
      element (TonE) consensus sequence was found at -578 to -568 in human CYP2E1 5'
      flanking region, and electrophoretic mobility shift assay demonstrated the
      interaction of TonE binding protein (TonEBP) with TonE motif of CYP2E1 promoter.
      Furthermore, cotransfection of a CYP2E1 promoter construct with wild-type TonEBP
      expression vector enhanced promoter activity under both isotonic and hypertonic
      conditions, whereas dominant-negative TonEBP suppressed an induction of CYP2E1
      promoter activity. These results indicate that the level of CYP2E1 is induced by
      hypertonic condition via TonEBP transactivation. The present study suggests that
      osmotic status may influence individual responses to the substrate of CYP2E1.

PMID- 17440117
TI  - Chronic intermittent ethanol treatment selectively alters N-methyl-D-aspartate
      receptor subunit surface expression in cultured cortical neurons.
AB  - A chronic intermittent ethanol (CIE) exposure regimen consists of repeated
      episodes of ethanol intoxication and withdrawal. CIE treatment has been reported
      to result in a significant enhancement of N-methyl-D-aspartate (NMDA) receptor
      mediated synaptic responses in vivo, and trafficking of NMDA receptors is
      emerging a key regulatory mechanism that underlies the channel function.
      Therefore, in the present study, we examined the effects of CIE on NMDA receptor
      subunit surface expression. Cultured cortical neurons were exposed to 75 mM
      ethanol for 14 h followed by 10 h of withdrawal, repeated this cycle five times,
      and followed by 2 or 5 days of withdrawal. Surface-expressed NMDA receptor
      subunits and their endocytosis were measured by biotinylation and Western blots.
      CIE significantly increased NMDA receptor (NR) 1 and NR2B but not NR2A subunit
      surface expression after 5 days of treatment. However, CIE treatment did not
      reduce the NMDA receptor endocytosis. Quantification of immunocytochemistry
      confirmed CIE-induced increase in both the total number of NR1 and NR2B subunit
      clusters and their targeting to synaptic sites. It is noteworthy that this effect
      persisted even after ethanol withdrawal with a peak expression occurring between
      0 and 2 days after withdrawal, and the expression on the plasma membrane was
      still at high levels after 5 days of withdrawal. In addition, this was
      accompanied by significant increases in postsynaptic density protein 95 clusters.
      Protein kinase A inhibitor completely reversed CIE-induced increase in NR1 and
      partially in NR2B surface level and a long-lasting effect. These changes may
      contribute to the development of ethanol-induced neurotoxicity and ethanol
      dependence.

PMID- 17440118
TI  - Activated neutrophils inhibit nucleotide excision repair in human pulmonary
      epithelial cells: role of myeloperoxidase.
AB  - Neutrophils are thought to affect pulmonary carcinogenesis by promoting the
      metabolism of inhaled chemical carcinogens, causing enhanced formation of
      promutagenic DNA adducts. We hypothesized that neutrophils interfere with the
      removal of such DNA adducts by inhibiting nucleotide excision repair (NER) in
      target cells. Human alveolar epithelial cells (A549) were cocultured with
      activated neutrophils, and we observed a significant reduction of NER in the A549
      cells, which was abrogated by addition of the myeloperoxidase (MPO) inhibitor 4
      aminobenzoic acid hydrazide. The inhibitory effect of neutrophils could be
      mimicked by the MPO product hypochlorous acid (HOCl), which caused an acute, dose
      dependent inhibition of NER in A549 cells. This was independent of cytotoxicity
      or ATP loss and persisted up to 24 h. These data were supported by showing that
      HOCl caused a delayed removal of DNA adducts in benzo[a]pyrene-diolepoxide
      exposed A549 cells. The acute HOCl-induced inhibition of NER can only partly be
      explained by oxidative modification of repair proteins. To explain the more
      persistent effects of HOCl, we analyzed the expression of NER genes and found
      that HOCl significantly reduced XPC expression. In conclusion, these data
      indicate that neutrophils are potent inhibitors of nucleotide excision repair.
      This may provide a further biological explanation for the association between
      inflammation and lung cancer development.

PMID- 17440120
TI  - Health trends in the elderly population: getting better and getting worse.
AB  - Health trends in the fastest growing sector of the population, the oldest old,
      have received much attention during the past decade because of the rising costs
      of medical and long-term care. Many studies have suggested a compression of
      morbidity in this sector, implying that the future care needs of elderly people
      will not follow the demographic prognoses. Most of these studies have used health
      indicators based on disability, a concept that is contextually embedded. We have
      taken a closer look at health-trend surveys with a focus on the health indicator
      used. Our findings reveal that although disability measures often show
      improvement, there is a simultaneous increase in chronic disease and functional
      impairments-health components that require care resources. That is, an expansion
      of other health problems may accompany a compression of disability. Therefore, a
      concept of general morbidity is not sufficient when discussing health trends and
      the need for care services in the elderly population. Because different
      indicators do not show the same trends over time, we suggest a more refined
      discussion that distinguishes between different health components. In addition,
      different components have different implications for the amount and kind of care
      resources needed. If the current positive trends in disability continue, future
      need for social services and long-term care may not parallel demographic
      projections. Trends in disease and functional limitations seem to have taken a
      different direction, suggesting a parallel or increased need for resources in
      medical care, rehabilitation, and compensatory interventions such as assistive
      technology.

PMID- 17440119
TI  - The endocannabinoid 2-arachidonoyl glycerol induces death of hepatic stellate
      cells via mitochondrial reactive oxygen species.
AB  - The endocannabinoid system is an important regulator of hepatic fibrogenesis. In
      this study, we determined the effects of 2-arachidonoyl glycerol (2-AG) on
      hepatic stellate cells (HSCs), the main fibrogenic cell type in the liver.
      Culture-activated HSCs were highly susceptible to 2-AG-induced cell death with
      >50% cell death at 10 microM after 18 h of treatment. 2-AG-induced HSC death
      showed typical features of apoptosis such as PARP- and caspase 3-cleavage and
      depended on reactive oxygen species (ROS) formation. Confocal microscopy revealed
      mitochondria as primary site of ROS production and demonstrated mitochondrial
      depolarization and increased mitochondrial permeability after 2-AG treatment. 2
      AG-induced cell death was independent of cannabinoid receptors but required the
      presence of membrane cholesterol. Primary hepatocytes were resistant to 2-AG
      induced ROS induction and cell death but became susceptible after GSH depletion
      suggesting antioxidant defenses as a critical determinant of 2-AG sensitivity.
      Hepatic levels of 2-AG were significantly elevated in two models of experimental
      fibrogenesis and reached concentrations that are sufficient to induce death in
      HSCs. These findings suggest that 2-AG may act as an antifibrogenic mediator in
      the liver by inducing cell death in activated HSCs but not hepatocytes.

PMID- 17440121
TI  - Perception gap in quality-of-life ratings: an empirical investigation of nursing
      home residents and caregivers.
AB  - PURPOSE: Several studies have previously documented the existence of a perception
      gap-the extent to which quality-of-life ratings provided by nursing home
      residents and caregivers diverge. In this study we use Helson's adaptation-level
      theory to investigate three types of antecedents: (a) focal factors, (b)
      background factors, and (c) residual factors. DESIGN AND METHODS: We calculated
      the perception gap for 11 quality-of-life domains. Caregivers rated both job
      satisfaction and their perception of quality of life of residents in the unit
      where they provided service. Concurrently, residents from these units completed
      quality-of-life interviews. We computed the perception gap by subtracting the
      residents' ratings from the caregivers' ratings for each quality-of-life domain.
      We conducted a hierarchical linear model using 3,850 observations to predict the
      perception gap. RESULTS: Caregivers perceive quality of life to be lower than
      residents do across all domains fairly consistently. Caregiver demographics do
      not directly predict the perception gap. However, satisfaction with work, pay,
      and promotion were significant predictors (p <.05), and satisfaction with
      supervisor was a marginally significant predictor (p <.10), of the perception
      gap. As satisfaction with these job dimensions increased, the perception gap
      decreased. Additional models show that several caregiver demographics directly
      influence job-satisfaction dimensions, though they did not influence the
      perception gap. IMPLICATIONS: Job-satisfaction dimensions, rather than caregiver
      characteristics, are the appropriate predictors of the perception gap. However,
      caregiver demographics exert their influence indirectly by means of job
      satisfaction. A key finding is that higher job satisfaction leads to a smaller
      perception gap. Helson's adaptation-level theory appears to be a useful approach
      for understanding the antecedents of the perception gap.

PMID- 17440122
TI  - Exploring the cost and value of private versus shared bedrooms in nursing homes.
AB  - PURPOSE: There is debate about the relative merits and costs of private versus
      shared bedrooms in nursing homes, particularly in light of the current efforts at
      creating both cost-efficient and person-centered care facilities. The purpose of
      this project was to explore the extent to which there is evidence-based
      information that supports the merits of three different bedroom configurations:
      traditional shared, enhanced shared, and private. DESIGN AND METHODS: We
      developed a framework of four broad domains that were related to the different
      bedroom configurations: psychosocial, clinical, operational, and construction or
      building factors. Within each dimension, we identified individual factors through
      the literature, interviews, and focus groups, with the goal of determining the
      breadth, depth, and quality of evidence supporting the benefits of one
      configuration over another. RESULTS: The vast majority of factors identified in
      this study, regardless of whether there was solid empirical data, information
      from the focus groups, or other anecdotal evidence, indicated better outcomes
      associated with private rooms over shared rooms in nursing homes. Cost estimates
      suggest that construction cost (plus debt service) differences range from roughly
      $20,506 per bed for a traditional shared room to $36,515 for a private one, and
      that such differences are recouped in less than 2 years if beds are occupied, and
      in less than 3 months if a shared bed remains unoccupied at average private-pay
      room costs. IMPLICATIONS: Despite limited empirical evidence in some areas, this
      project provides the foundation for an evidence-based life-cycle costing
      perspective regarding the relative merits of different bedroom configurations.

PMID- 17440123
TI  - A preliminary evaluation of the paid feeding assistant regulation: impact on
      feeding assistance care process quality in nursing homes.
AB  - PURPOSE: The Centers for Medicare and Medicaid Services and the Agency for
      Healthcare Research and Quality sponsored a nationwide study to evaluate the
      federal paid feeding assistant (PFA) regulation that allows nursing homes to hire
      single-task workers to provide feeding assistance to nursing home residents.
      Organizers designed the PFA regulation to increase the number of staff available
      to provide assistance with eating and improve nutritional care process quality.
      DESIGN AND METHODS: Trained research staff used standardized protocols to conduct
      direct observations during meals and face-to-face staff interviews in a
      convenience sample of seven facilities with PFA programs to evaluate care process
      quality. RESULTS: Most (84%) of the trained PFAs in the seven site visit
      facilities were non-nursing staff within the facility; the quality of feeding
      assistance care provided by these workers was comparable to that provided by
      indigenous nurse aides. There were no reported changes in existing staffing
      levels (nurse aide or licensed nurses) following PFA program implementation, and
      the majority (> 90%) of indigenous staff at all levels reported positive benefits
      of the PFA program for both staff and residents. IMPLICATIONS: Findings from this
      preliminary study indicate that the PFA regulation may serve to increase the
      utilization of existing non-nursing staff to improve feeding assistance care
      during meals without having a negative impact on existing nurse aide and licensed
      nurse staffing levels.

PMID- 17440124
TI  - Job satisfaction of nurse aides in nursing homes: intent to leave and turnover.
AB  - PURPOSE: The relationship between job satisfaction of nurse aides and intent to
      leave and actual turnover after 1 year is examined. DESIGN AND METHODS: Data came
      from a random sample of 72 nursing homes from 5 states (Colorado, Florida,
      Michigan, New York, and Oregon). From these nursing homes, we collected 1,779
      surveys from nurse aides (a response rate of 62%). We used a job satisfaction
      instrument specifically developed for use with nurse aides, as well as previously
      validated measures of intent to leave and turnover. We used ordered logistic
      regression and logistic regression to examine the data. RESULTS: High overall job
      satisfaction was associated with low scores on thinking about leaving, thinking
      about a job search, searching for a job, and turnover. In examining the
      association between the job satisfaction subscales and intent to leave and
      turnover, we found that high Work Schedule subscale scores, high Training
      subscale scores, and high Rewards subscale scores were associated with low scores
      on thinking about leaving, thinking about a job search, searching for a job, and
      turnover. High scores on the Quality of Care subscale were associated with low
      turnover after 1 year. IMPLICATIONS: These results are important in clearly
      showing the relationship between job satisfaction and intent to leave and
      turnover of nurse aides. Training, rewards, and workload are particularly
      important aspects of nurse aides' jobs.

PMID- 17440125
TI  - Assessment of the efficacy of a stress management program for informal caregivers
      of dependent older adults.
AB  - PURPOSE: The majority of dependent older adults receive care at home from a
      family member. Caregiving places enormous demands on these caregivers and the
      negative consequences associated with caregiving are well documented. In this
      study we compared the effectiveness of two active interventions to a waiting-list
      control condition to improve emotional well-being in family caregivers. DESIGN
      AND METHODS: We randomized distressed caregivers (N = 91) of physically impaired
      older adults to one of three conditions: traditional weekly sessions, minimal
      therapist-contact sessions, or a waiting-list control group. These manual-guided
      interventions took place over a 2-month period. RESULTS: Caregivers in the
      traditional weekly sessions experienced the highest reduction in depressive and
      anxious symptoms. Compared with control participants, caregivers in the
      traditional weekly sessions had lower posttreatment levels of depression and
      anxiety. They had also lower levels of depression than did caregivers in the
      minimal-therapist-contact intervention. IMPLICATIONS: These data suggest that
      traditional weekly sessions may be effective in reducing caregiver anxiety and
      depression. They further suggest that traditional weekly sessions are better than
      no intervention, and they are also better than a minimal-therapist-contact
      intervention.

PMID- 17440126
TI  - The role of perceived control in explaining depressive symptoms associated with
      driving cessation in a longitudinal study.
AB  - PURPOSE: The purpose of this article was to investigate the role of control
      beliefs in mediating the relationship between driving cessation and change in
      depressive symptoms in a population-based sample of older adults. DESIGN AND
      METHODS: We report results from a prospective, community-based cohort study that
      included two waves of data collected in 1992 and 1994. Participants consisted of
      700 men and women aged 70 and older, including 647 drivers and 53 participants
      who ceased driving between baseline (1992) and follow-up (1994). Participants
      took part in interviews that included assessments of driving status,
      sociodemographic characteristics, self-rated health, sensory function, depressive
      symptoms (through the Center for Epidemiologic Studies-Depression scale), and
      expectancy of control. Using multilevel general linear models, we examined the
      extent to which driving status, expectancy of control, and relevant covariates
      explained change in depressive-symptom scores between baseline and follow-up.
      RESULTS: Driving cessation was associated with an increase in depressive symptoms
      from baseline to follow-up. The higher depressive-symptom scores of ceased
      drivers relative to those of individuals who remained drivers at both waves was
      partly explained by a corresponding decrease in the sense of control among ceased
      drivers, and increased control beliefs among drivers. IMPLICATIONS: Interventions
      aimed at promoting the maintenance of personal agency and associated control
      beliefs could be protective against the negative psychological concomitants of
      driving cessation.

PMID- 17440127
TI  - The economic consequences of widowhood for older minority women.
AB  - PURPOSE: We compare the economic consequences of widowhood for pre-retirement age
      and early-retirement age Black, Hispanic, and non-Hispanic White women. METHODS:
      We use the 1992 and 2000 waves of the Health and Retirement Study to assess the
      effects of widowhood on the household incomes and assets of non-Hispanic White,
      Black, and Hispanic women who were 51 years of age or older at baseline (N =
      4,544). RESULTS: For women of all racial and ethnic groups, marital disruption,
      including widowhood, results in a substantial decline in household income and
      assets. Net of demographic controls, the relative loss is far greater for Black
      and Hispanic widows than for non-Hispanic White widows. IMPLICATIONS: The data
      reveal a substantial widowhood penalty for total household income and net worth
      for women in each racial and ethnic group. However, the findings suggest that
      minority widows are at a particularly high risk of poverty in late life, given
      that they have lower incomes and fewer assets to begin with. Implications of the
      results for the financial security of women approaching retirement are discussed.

PMID- 17440128
TI  - The Arkansas aging initiative: an innovative approach for addressing the health
      of older rural Arkansans.
AB  - The Donald W. Reynolds Institute on Aging at the University of Arkansas for
      Medical Sciences in Little Rock is addressing one of the most pressing policy
      issues facing the United States: how to care for the burgeoning number of older
      adults. In 2001, the Institute created the Arkansas Aging Initiative, which
      established seven satellite centers on aging across the state using $1.3 to $2
      million dollars annually from the state's portion of the Master Tobacco
      Settlement. These centers on aging assist the state's population of older adults,
      many of whom reside in rural areas, live in poverty, and suffer from poor health.
      The centers provide multiple avenues of education for the community, health care
      providers, families, and caregivers. The Arkansas Aging Initiative, in
      partnership with local hospitals, also makes geriatric primary and specialty care
      more accessible through senior health clinics established across rural Arkansas.
      In 2005, older adults made more than 36,000 visits to these clinics. All sites
      have attracted at least one physician who holds a Certificate of Added
      Qualifications in geriatrics and one advanced practice nurse. Other team members
      include geriatric medical social workers, pharmacists, nutritionists, and
      neuropsychologists. This initiative also addresses other policy issues, including
      engaging communities in building partnerships and programs crucial to maximizing
      their limited resources and identifying opportunities to change reimbursement
      mechanisms for care provided to the growing number of older adults. We believe
      this type of program has the potential to create a novel paradigm for nationwide
      implementation.

PMID- 17440129
TI  - Helping people make better long-term-care decisions.
AB  - PURPOSE: The purpose of this article is to describe an innovative online system
      to support long-term-care decision making. DESIGN AND METHODS: The Long-Term Care
      Choices tool is a web-based system that uses expert opinion and structures
      decision making. RESULTS: The system has been well accepted, and most users find
      it easy to use. IMPLICATIONS: Other states could adopt similar systems to help
      people navigate the long-term-care system.

PMID- 17440130
TI  - Drawing on wisdom from the past: an elder abuse intervention with tribal
      communities.
AB  - PURPOSE: The Family Care Conference (FCC) is an elder-focused, family-centered,
      community-based intervention for the prevention and mitigation of elder abuse. It
      is based on a family conference intervention developed by the Maori people of New
      Zealand, who determined that Western European ways of working with child welfare
      issues were undermining such family values as the definition and meaning of
      family, the importance of spirituality, the use of ritual, and the value of non
      interference. The FCC provides the opportunity for family members to come
      together to discuss and develop a plan for the well-being of their elders. DESIGN
      AND METHODS: Using a community-based participatory research approach,
      investigators piloted and implemented the FCC in one northwestern Native American
      community. The delivery of the FCC intervention has grown from having been
      introduced and facilitated by the researchers, to training community members to
      facilitate the family meetings, to becoming incorporated into a Tribal agency,
      which will oversee the implementation of the FCC. RESULTS: To date, families have
      accepted and appreciated the FCC intervention. The constructive approach of the
      FCC process helps to bring focus to families' concerns and aligns their efforts
      toward positive action. IMPLICATIONS: The strength-based FCC provides a
      culturally anchored and individualized means of identifying frail Native American
      elders' needs and finding solutions from family and available community
      resources.

PMID- 17440132
TI  - Regulation of PC12 cell differentiation by cAMP signaling to ERK independent of
      PKA: do all the connections add up?
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that
      elevates adenosine 3',5'-monophosphate (cyclic AMP, also abbreviated cAMP) to
      elicit neuritogenesis in PC12 cells. This effect appears to be independent of
      cAMP-dependent protein kinase (PKA) yet dependent on cAMP, leading to the
      conclusion that another cAMP-binding protein and subsequent signaling pathway
      must exist to mediate this PKA-independent signaling mechanism. Such a protein
      was identified as exchange protein directly activated by cAMP (EPAC). Although
      EPAC may play an indirect role in PACAP-mediated neuritogenesis, it does not
      serve as the only PKA-independent link from cAMP that leads to neuritogenesis.
      Thus, the challenge remains to construct a signaling network that incorporates
      the known mediators, working independently of PKA, that are ultimately
      responsible for PACAP-mediated neuritogenesis.

PMID- 17440133
TI  - The cover. Le rendezvous des chats.

PMID- 17440134
TI  - A piece of my mind. Holding.

PMID- 17440135
TI  - Mental health courts show promise.

PMID- 17440136
TI  - Genetic flaw linked to early heart disease: association with osteoporosis also
      found.

PMID- 17440137
TI  - New European funding agency backs "blue-skies" research.

PMID- 17440138
TI  - Diabetes drugs tied to fractures in women.

PMID- 17440139
TI  - Outcomes of treatment vs observation of localized prostate cancer in elderly men.

PMID- 17440140
TI  - Outcomes of treatment vs observation of localized prostate cancer in elderly men.

PMID- 17440141
TI  - Outcomes of treatment vs observation of localized prostate cancer in elderly men.

PMID- 17440142
TI  - Outcomes of treatment vs observation of localized prostate cancer in elderly men.

PMID- 17440143
TI  - Prediction rule for bacterial meningitis in children.

PMID- 17440144
TI  - Dialysis facility ownership and epoetin dosing in patients receiving
      hemodialysis.
AB  - CONTEXT: Epoetin therapy for dialysis-related anemia is the single largest
      Medicare drug expenditure. The type of facility (profit, chain, and affiliation
      status) at which a patient receives dialysis might affect epoetin dosing patterns
      and has implications for future epoetin policies. OBJECTIVE: To examine the
      association between dialysis facility ownership and the dose of epoetin
      administered. DESIGN, SETTING, AND PARTICIPANTS: Data from the US Renal Data
      System were used to identify 159,522 adult Medicare-eligible, end-stage renal
      disease patients receiving in-center hemodialysis during November and December
      2004. Regression models were used to estimate the mean epoetin dose and dose
      adjustment by profit, chain, and affiliation status. MAIN OUTCOME MEASURES:
      Weekly mean epoetin dose administered in December 2004 and the adjustment in dose
      between November and December 2004. RESULTS: Compared with patients in nonprofit
      dialysis facilities (n = 28,199), patients in large for-profit dialysis chain
      facilities (n = 106,116) were consistently administered the highest doses of
      epoetin regardless of anemia status. Compared with nonprofit facilities, for
      profit facilities administered, on average, an additional 3306 U/wk of epoetin.
      Among the 6 large chain facilities with a similar patient case-mix, the average
      dose of epoetin ranged from 17,832 U/wk at chain 5 (nonprofit facilities with a
      mean hematocrit level of 34.6%) to 24,986 U/wk at chain 2 (for-profit facilities
      with a mean hematocrit level of 36.5%). Dosing adjustments also differed by type
      of facility. On average, compared with nonprofit facilities, for-profit
      facilities increased epoetin doses 3-fold for patients with hematocrit levels of
      less 33% and also increased the doses among patients with hematocrit levels in
      the recommended target of 33% to 36%, especially in the largest for-profit chain
      facilities. The greatest difference in dosing practice patterns between
      facilities was found among patients with hematocrit levels of less than 33%.
      CONCLUSIONS: Dialysis facility organizational status and ownership are associated
      with variation in epoetin dosing in the United States. Different epoetin dosing
      patterns suggest that large for-profit chain facilities used larger dose
      adjustments and targeted higher hematocrit levels.

PMID- 17440145
TI  - Clinical response and risk for reported suicidal ideation and suicide attempts in
      pediatric antidepressant treatment: a meta-analysis of randomized controlled
      trials.
AB  - CONTEXT: The US Food and Drug Administration (FDA) has issued warnings that use
      of antidepressant medications poses a small but significantly increased risk of
      suicidal ideation/suicide attempt for children and adolescents. OBJECTIVE: To
      assess the efficacy and risk of reported suicidal ideation/suicide attempt of
      antidepressants for treatment of pediatric major depressive disorder (MDD),
      obsessive-compulsive disorder (OCD), and non-OCD anxiety disorders. DATA SOURCES
      AND STUDY SELECTION: PubMed (1988 to July 2006), relevant US and British
      regulatory agency reports, published abstracts of important scientific meetings
      (1998-2006), clinical trial registries, and information from authors. Studies
      were published and unpublished randomized, placebo-controlled, parallel-group
      trials of second-generation antidepressants (selective serotonin reuptake
      inhibitors, nefazodone, venlafaxine, and mirtazapine) in participants younger
      than 19 years with MDD, OCD, or non-OCD anxiety disorders. DATA EXTRACTION:
      Information was extracted on study characteristics, efficacy outcomes, and
      spontaneously reported suicidal ideation/suicide attempt. DATA SYNTHESIS: Twenty
      seven trials of pediatric MDD (n = 15), OCD (n = 6), and non-OCD anxiety
      disorders (n = 6) were selected, and risk differences for response and for
      suicidal ideation/suicide attempt estimated by random-effects methods. Pooled
      risk differences in rates of primary study-defined measures of responder status
      significantly favored antidepressants for MDD (11.0%; [95% confidence interval
      {CI}, 7.1% to 14.9%]), OCD (19.8% [95% CI, 13.0% to 26.6%), and non-OCD anxiety
      disorders (37.1% [22.5% to 51.7%]), corresponding to a number needed to treat
      (NNT) of 10 (95% CI, 7 to 15), 6 (4 to 8), and 3 (2 to 5), respectively. While
      there was increased risk difference of suicidal ideation/suicide attempt across
      all trials and indications for drug vs placebo (0.7%; 95% CI, 0.1% to 1.3%)
      (number needed to harm, 143 [95% CI, 77 to 1000]), the pooled risk differences
      within each indication were not statistically significant: 0.9% (95% CI, -0.1% to
      1.9%) for MDD, 0.5% (-1.2% to 2.2%) for OCD, and 0.7% (-0.4% to 1.8%) for non-OCD
      anxiety disorders. There were no completed suicides. Age-stratified analyses
      showed that for children younger than 12 years with MDD, only fluoxetine showed
      benefit over placebo. In MDD trials, efficacy was moderated by age, duration of
      depression, and number of sites in the treatment trial. CONCLUSIONS: Relative to
      placebo, antidepressants are efficacious for pediatric MDD, OCD, and non-OCD
      anxiety disorders, although the effects are strongest in non-OCD anxiety
      disorders, intermediate in OCD, and more modest in MDD. Benefits of
      antidepressants appear to be much greater than risks from suicidal
      ideation/suicide attempt across indications, although comparison of benefit to
      risk varies as a function of indication, age, chronicity, and study conditions.

PMID- 17440146
TI  - A 60-year-old woman considering acupuncture for knee pain.
AB  - Mrs A, an active 60-year-old woman, has a history of degenerative osteoarthritis
      of her knee with pain that has progressed over the past 8 years. She has
      undergone arthroscopic surgery for a meniscal tear and has taken nonsteroidal
      anti-inflammatory drugs (NSAIDs), glucosamine, and chondroitin sulfate
      occasionally, but generally does not like taking medications. She is open to
      other therapeutic approaches and wants to know if acupuncture can help the pain,
      improve function, and stop her condition from progressing. The evidence for the
      effectiveness of acupuncture for knee pain and other common treatments, including
      exercise, NSAIDs, glucosamine and chondroitin, and intra-articular knee
      injections are compared, and costs and methods of acupuncture and selecting an
      acupuncturist are discussed.

PMID- 17440147
TI  - The pandemic and All-Hazards Preparedness Act: improving public health emergency
      response.

PMID- 17440148
TI  - Lack of benefit from nitric oxide synthase inhibition in patients with
      cardiogenic shock: looking for the reasons.

PMID- 17440149
TI  - Use of epoetin in chronic renal failure.

PMID- 17440150
TI  - JAMA patient page. Knee pain.

PMID- 17440151
TI  - Patient safety in cancer care: a time for action.

PMID- 17440152
TI  - Adjuvant therapy for gastric cancer: how negative results can help patients.

PMID- 17440153
TI  - More aspirin for less cancer?

PMID- 17440154
TI  - FDA clarifies rules for getting experimental drugs.

PMID- 17440155
TI  - Public support for smoking bans diffusing to developing countries.

PMID- 17440156
TI  - Breast cancer stamp funds new NCI program.

PMID- 17440157
TI  - Stat bite: Breast cancer stamp sales.

PMID- 17440159
TI  - Liver cancer biomarkers struggling to succeed.

PMID- 17440160
TI  - Potential drug interactions and duplicate prescriptions among cancer patients.
AB  - BACKGROUND: Cancer patients receive numerous medications, including
      antineoplastic agents, drugs for supportive care, and medications for comorbid
      illnesses. Therefore, they are at risk for drug interactions and duplicate
      prescribing. METHODS: A questionnaire eliciting information on demographics and
      medications taken in the previous 4 weeks was given to adult outpatients
      receiving systemic anticancer therapy for solid tumors. The Drug Interaction
      Facts software, version 4.0, was used to identify potential drug interactions and
      to classify them by level of severity (major, moderate, or minor) and the
      strength of scientific evidence for them (using categories [1-5] of decreasing
      certainty). Summary statistics and logistic regression were used to analyze the
      data. All statistical tests were two-sided. RESULTS: The survey was completed by
      405 patients. We observed 276 potential drug interactions, and at least one
      potential interaction was identified in 109 patients (27%; 95% confidence
      interval [CI] = 23% to 31%). Of the potential interactions, 25 (9%) were
      classified as major and 211 (77%) as moderate. Nearly half (49%) of potential
      interactions were supported by level 1 or 2 scientific evidence. Most potential
      drug interactions (87%) involved non-anticancer agents such as warfarin,
      antihypertensive drugs, corticosteroids, and anticonvulsants, but some (n = 36,
      13%) involved antineoplastic agents. In multivariable analysis, increased risk of
      receiving drug combinations in which there were potential drug interactions was
      associated with receipt of increasing numbers of drugs (odds ratio [OR] = 1.4 per
      additional drug, 95% CI = 1.26 to 1.58, P<.001 from the Wald chi-square test),
      type of medication (drugs to treat comorbid conditions versus supportive care
      medications only; OR = 8.6, 95% CI = 2.9 to 25, P<.001), and the presence of
      brain tumors. Thirty-two (8%) patients were exposed to duplicate medications,
      most often corticosteroids, proton pump inhibitors, or benzodiazepines.
      CONCLUSION: Potential drug interactions were common among cancer patients and
      most often involved medications to treat comorbid conditions. Duplicate
      medications were infrequent.

PMID- 17440161
TI  - Adjuvant treatment of high-risk, radically resected gastric cancer patients with
      5-fluorouracil, leucovorin, cisplatin, and epidoxorubicin in a randomized
      controlled trial.
AB  - BACKGROUND: Promising findings obtained using a weekly regimen of 5-fluorouracil
      (5-FU), epidoxorubicin, leucovorin (LV), and cisplatin (PELFw) to treat locally
      advanced and metastatic gastric cancer prompted the Italian Group for the Study
      of Digestive Tract Cancer (GISCAD) to investigate the efficacy of this regimen as
      adjuvant treatment for high-risk radically resected gastric cancer patients.
      METHODS: From January 1998 to January 2003, 400 gastric cancer patients at high
      risk for recurrence including patients with serosal invasion (stage pT3 N0)
      and/or lymph node metastasis (stage pT2 or pT3 N1, N2, or N3), were enrolled in a
      trial of adjuvant chemotherapies; 201 patients were randomly assigned to receive
      the PELFw regimen, consisting of eight weekly administrations of cisplatin (40
      mg/m2), LV (250 mg/m2), epidoxorubicin (35 mg/m2), 5-FU (500 mg/m2), and
      glutathione (1.5 g/m2) with the support of filgrastim, and 196 patients were
      assigned to a regimen consisting of six monthly administrations of a 5-day course
      of 5-FU (375 mg/m2 daily) and LV (20 mg/m2 daily, 5-FU/LV). Disease-free and
      overall survival were estimated and compared between arms using hazard ratios
      (HRs) and Kaplan-Meier estimates. All statistical tests were two-sided. RESULTS:
      The 5-year survival rates were 52% in the PELFw arm and 50% in the 5-FU/LV arm.
      Compared with the 5-FU/LV regimen, the PELFw regimen did not reduce the risk of
      death (HR = 0.95, 95% confidence interval [CI] = 0.70 to 1.29) or relapse (HR =
      0.98, 95% CI = 0.75 to 1.29). Less than 10% of patients in either arm experienced
      a grade 3 or 4 toxic episode. Neutropenia (occurring more often in the PELFw arm)
      and diarrhea and mucositis (more prevalent in the 5-FU/LV arm) were the most
      common serious side effects. Nevertheless, only 19 patients (9.4%) completed the
      treatment in the PELFw arm and 85 (43%) patients completed the treatment in the 5
      FU/LV arm. CONCLUSIONS: Our study found no benefit from an intensive weekly
      chemotherapy in gastric cancer. The extent of toxicity experienced by the
      patients in the adjuvant setting suggests that, in gastric cancer, chemotherapy
      may be more safely administered preoperatively.

PMID- 17440162
TI  - A large cohort study of long-term daily use of adult-strength aspirin and cancer
      incidence.
AB  - BACKGROUND: Epidemiologic evidence indicates that aspirin use is associated with
      reduced risks of colon cancer and possibly several other cancers, including
      prostate and breast cancers. Recent results from the Women's Health Study
      randomized trial indicate that long-term use of low-dose aspirin (100 mg every
      other day) does not substantially reduce cancer risk. However, the potential
      effect of long-term daily use of higher doses of aspirin on cancer incidence
      remains uncertain. METHODS: We examined associations between long-term daily use
      of adult-strength aspirin (> or = 325 mg/day) and both overall cancer incidence
      and incidence of 10 types of cancer among 69,810 men and 76,303 women
      participating in the Cancer Prevention Study II Nutrition Cohort, a relatively
      elderly population. Aspirin use was reported at enrollment in 1992-1993 and
      updated in 1997, 1999, and 2001. Multivariable Cox proportional hazards
      regression was used to calculate rate ratios (RRs). RESULTS: During follow-up
      through June 2003, 10,931 men and 7196 women were diagnosed with cancer. Long
      term (> or = 5 years) daily use of adult-strength aspirin, compared with no use,
      was associated with lower overall cancer incidence in men (multivariable-adjusted
      RR = 0.84, 95% confidence interval [CI] = 0.76 to 0.93) and non-statistically
      significantly lower overall cancer incidence in women (multivariable-adjusted RR
      = 0.86, 95% CI = 0.73 to 1.03). Overall cancer incidence per 100,000 person-years
      (standardized to the age distributions of men and women in the study) with long
      term daily aspirin use and no aspirin use was 1858 and 2163, respectively, among
      men and 1083 and 1169, respectively, among women. Long-term daily aspirin use was
      associated with lower incidence of colorectal cancer (RR = 0.68, 95% CI = 0.52 to
      0.90 among men and women combined) and prostate cancer (RR = 0.81, 95% CI = 0.70
      to 0.94) and a non-statistically significant lower risk of female breast cancer
      (RR = 0.83, 95% CI = 0.63 to 1.10). CONCLUSIONS: Long-term daily use of adult
      strength aspirin may be associated with modestly reduced overall cancer incidence
      in populations among whom colorectal, prostate, and breast cancers are common.

PMID- 17440163
TI  - Novel cell culture technique for primary ductal carcinoma in situ: role of Notch
      and epidermal growth factor receptor signaling pathways.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) and Notch signaling
      pathways have been implicated in self-renewal of normal breast stem cells. We
      investigated the involvement of these signaling pathways in ductal carcinoma in
      situ (DCIS) of the breast. METHODS: Samples of normal breast tissue (n = 15),
      pure DCIS tissue of varying grades (n = 35), and DCIS tissue surrounding an
      invasive cancer (n = 7) were used for nonadherent (i.e., mammosphere) culture.
      Mammosphere cultures were treated at day 0 with gefitinib (an EGFR inhibitor),
      DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester) (a
      gamma-secretase inhibitor), or Notch 4-neutralizing antibody. Mammosphere-forming
      efficiency (MFE) was calculated by dividing the number of mammospheres of 60
      microm or more formed by the number of single cells seeded and is expressed as a
      percentage. The Notch 1 intracellular domain (NICD) was detected
      immunohistochemically in paraffin-embedded DCIS tissue from 50 patients with at
      least 60 months of follow-up. All statistical tests were two-sided. RESULTS: DCIS
      had a greater MFE than normal breast tissue (1.5% versus 0.5%, difference = 1%,
      95% confidence interval [CI] = 0.62% to 1.25%, P<.001). High-grade DCIS had a
      greater MFE than low-grade DCIS (1.6% versus 1.09%, difference = 0.51%, 95% CI =
      0.07% to 0.94%, P = .01). The MFE of high-grade DCIS treated with gefitinib in
      the absence of exogenous EGF was lower than that of high-grade DCIS treated with
      mammosphere medium lacking gefitinib and exogenous EGF (0.56% versus 1.36%,
      difference 0.8%, 95% CI = 0.33% to 1.4%, P = .004). Increased Notch signaling as
      detected by NICD staining was associated with recurrence at 5 years (P = .012).
      DCIS MFE was reduced when Notch signaling was inhibited using either DAPT (0.89%
      versus 0.51%, difference = 0.38%, 95% CI = 0.2% to 0.6%, P<.001) or a Notch 4
      neutralizing antibody (0.97% versus 0.2%, difference = 0.77%, 95% CI = 0.52% to
      1.0%, P<.001). CONCLUSION: We describe a novel primary culture technique for
      DCIS. Inhibition of the EGFR or Notch signaling pathways reduced DCIS MFE.

PMID- 17440164
TI  - Expression of p95HER2, a truncated form of the HER2 receptor, and response to
      anti-HER2 therapies in breast cancer.
AB  - BACKGROUND: Women with HER2-overexpressing breast cancers have poor prognosis,
      and many are resistant to the HER2 monoclonal antibody trastuzumab. A subgroup of
      HER2-overexpressing tumors also express p95HER2, an amino terminally truncated
      receptor that has kinase activity. Because p95HER2 cannot bind to trastuzumab but
      should be responsive to the HER2 tyrosine kinase inhibitor lapatinib, we compared
      the sensitivity of tumors expressing p95HER2 and tumors expressing the full
      length HER2 receptor to these agents. METHODS: MCF-7 and T47D breast cancer cells
      were stably transfected with either full-length HER2 or p95HER2. We studied the
      effects of trastuzumab and lapatinib on receptor signaling, cell proliferation,
      and the growth of xenograft tumors. A paraffin-based immunofluorescence assay was
      developed to study the association between p95HER2 expression and sensitivity to
      trastuzumab in patients with advanced breast cancer. All statistical tests were
      two-sided. RESULTS: Treatment of p95HER2-expressing cells with lapatinib
      inhibited p95HER2 phosphorylation, reduced downstream phosphorylation of Akt and
      mitogen-activated protein kinases, inhibited cell growth (MCF-7p95HER2 clones,
      lapatinib versus control, mean growth inhibition = 57.6% versus 22.6%, difference
      = 35%, 95% confidence interval [CI] = 22.5% to 47.3%; P<.001; T47Dp95HER2 clones,
      lapatinib versus control, mean growth inhibition = 36.8% versus 20%, difference =
      16.8%, 95% CI = 11.3% to 22.3%, P<.001), and inhibited growth of MCF-7p95HER2
      xenograft tumors (lapatinib versus control, mean = 288.8 versus 435 mm3,
      difference = 146.2 mm3, CI = 73.8 to 218.5 mm3, P = .002). By contrast, treatment
      with trastuzumab had no effect on any of these parameters. Of 46 patients with
      metastatic breast cancer who were treated with trastuzumab, only one of nine
      patients (11.1%) expressing p95HER2 responded to trastuzumab (with a partial
      response), whereas 19 of the 37 patients (51.4%) with tumors expressing full
      length HER2 achieved either a complete (five patients) or a partial (14 patients)
      response (P = .029). CONCLUSIONS: Breast tumors that express p95HER2 are
      resistant to trastuzumab and may require alternative or additional anti-HER2
      targeting strategies.

PMID- 17440165
TI  - The 1p-encoded protein stathmin and resistance of malignant gliomas to
      nitrosoureas.
AB  - BACKGROUND: Malignant gliomas are generally resistant to all conventional
      therapies. Notable exceptions are anaplastic oligodendrogliomas with loss of
      heterozygosity on chromosome 1p (1p+/-). Patients with 1p+/- anaplastic
      oligodendroglioma frequently respond to procarbazine, 1-(2-chloroethyl)-3
      cyclohexyl-l-nitrosourea, and vincristine. Because the underlying biologic basis
      for this clinical finding is unclear, we evaluated differentially expressed 1p
      encoded proteins in 1p+/- and 1p+/+ malignant glioma cell lines and then examined
      whether their expression was associated with outcome of patients with anaplastic
      oligodendroglioma. METHODS: We used a comparative proteomic screen of A172 (1p+/
      ) and U251 (1p+/+) malignant glioma cell lines to identify differentially
      expressed 1p-encoded proteins, including stathmin, a microtubule-associated
      protein. 1p+/- and 1p+/+ anaplastic oligodendroglioma specimens from 24 patients
      were assessed for stathmin expression by immunohistochemistry. The relationship
      between stathmin expression and clinical outcome was assessed with Kaplan-Meier
      analyses. RNA inhibition and cDNA transfection experiments tested effects of
      stathmin under- and overexpression, respectively, on the in vitro and in vivo
      resistance of malignant glioma cells to treatment with nitrosourea. For in vivo
      resistance studies, 36 mice with intracranial and 16 mice with subcutaneous
      xenograft tumor implants were used (one tumor per mouse). Flow cytometry was used
      for cell cycle analysis. Immunoblotting was used to assess protein expression.
      All statistical tests were two-sided. RESULTS: Decreased stathmin expression in
      tumors was statistically significantly associated with loss of heterozygosity in
      1p (P<.001) and increased recurrence-free survival (P<.001). The median
      recurrence-free survival times for patients with tumors expressing low,
      intermediate, or high stathmin levels were 45 months (95% confidence interval
      [CI] = 0 to 90 months), 17 months (95% CI = 10.6 to 23.4 months), and 6 months
      (95% CI = 1.7 to 10.3 months), respectively. Expression of stathmin was inversely
      associated with overall survival of nitrosourea-treated mice carrying xenograft
      tumors. Median survival of mice with stathmin+/- tumors was 95 days (95% CI =
      68.7 to 121.3 days) and that of mice with stathmin+/+ tumors was 64 days (95% CI
      = 58.2 to 69.8 days) (difference = 31 days, 95% CI = 4.1 to 57.9 days; P<.001,
      log-rank test). Nitrosoureas induced mitotic arrest in malignant glioma cells,
      and this effect was greater in cells with decreased stathmin expression.
      CONCLUSIONS: Loss of heterozygosity for the stathmin gene may be associated with
      improved outcomes of patients with 1p+/- anaplastic oligodendroglioma tumors.

PMID- 17440169
TI  - Re: Cellular telephone use and cancer risk: update of a nationwide Danish cohort
      study.

PMID- 17440166
TI  - Re: Human papillomavirus type 16 and 18 variants: race-related distribution and
      persistence.

PMID- 17440170
TI  - Impact of oral antihyperglycemic therapy on all-cause mortality among patients
      with diabetes in the Veterans Health Administration.
AB  - OBJECTIVE: The objective of this analysis was to evaluate the impact of several
      classes of oral antihyperglycemic therapy relative to sulfonylurea monotherapy on
      all-cause mortality among a cohort of patients with diabetes from the Veterans
      Health Administration (VHA). RESEARCH DESIGN AND METHODS: A retrospective cohort
      study using data obtained from the VHA Diabetes Epidemiology Cohort was used.
      Users of oral antihyperglycemic therapy were classified into the following
      cohorts: sulfonylurea monotherapy, metformin monotherapy, metformin plus
      sulfonylurea, thiazolidinedione (TZD) use alone or in combination with other oral
      agents (TZD users), and no drug therapy. All-cause mortality was the outcome of
      interest. Multivariate mixed models incorporating a propensity score to account
      for imbalance among cohorts were used to estimate drug effects on mortality with
      associated 95% CIs. RESULTS: A total of 39,721 patients with diabetes were
      included in the study. Adjusted odds ratios and 95% CIs for all-cause mortality
      were 0.87 (0.68-1.10) for metformin monotherapy users, 0.92 (0.82-1.05) for
      metformin plus sulfonylurea users, and 1.04 (0.75-1.46) for TZD users, relative
      to sulfonylurea monotherapy users. CONCLUSIONS: We did not find any significant
      drug effect on all-cause mortality for any oral treatment cohorts relative to
      sulfonylurea oral monotherapy.

PMID- 17440171
TI  - Glycemic index-based nutritional education improves blood glucose control in
      Japanese adults: a randomized controlled trial.

PMID- 17440172
TI  - Prognostic impact of metabolic syndrome by different definitions in a population
      with high prevalence of obesity and diabetes: the Strong Heart Study.
AB  - OBJECTIVE: This study analyzed which definition of the metabolic syndrome is more
      predictive of cardiovascular events in both diabetic and nondiabetic members of a
      population-based sample. RESEARCH DESIGN AND METHODS: A 10-year, longitudinal
      follow-up of the Strong Heart Study cohort has been evaluated. The analysis
      included 3,945 participants (2,384 female) with complete data (1,700 with
      diabetes and 1,468 with arterial hypertension) for evaluation of metabolic
      syndrome. Those with prevalent cardiovascular disease were excluded (n = 287, of
      whom 127 were female). Prevalence of metabolic syndrome was assessed based on the
      World Health Organization (WHO), the National Cholesterol Education Program Adult
      Treatment Panel (NCEP ATP) III, and International Diabetes Federation (IDF)
      definitions. The main outcome was 10-year incidence of combined fatal and
      nonfatal cardiovascular events, including stroke, coronary heart disease, and
      congestive heart failure. RESULTS: Fatal and nonfatal cardiovascular events
      occurred in 1,120 participants. After adjusting for age, sex, and diabetes,
      metabolic syndrome by all definitions was significantly associated with higher
      incidence of cardiovascular events (all P < 0.0001). In nondiabetic individuals,
      incident cardiovascular event rates were about 30-40% higher in those with
      metabolic syndrome, without a significant difference among definitions (0.03 < P
      < 0.001), and remained significant in WHO and NCEP ATP III definitions even after
      further adjustment for obesity, hypertension, and low HDL cholesterol. In the
      diabetic group, metabolic syndrome risk for cardiovascular events was greatest
      using the WHO definition (P < 0.002 vs. other models). CONCLUSIONS: In
      individuals without diabetes, metabolic syndrome is associated with incident
      cardiovascular disease, especially with WHO and NCEP ATP III definitions.
      Metabolic syndrome also predicts higher cardiovascular event rates in diabetic
      participants, a prediction that is greatest using the WHO definition.

PMID- 17440173
TI  - CD36-facilitated fatty acid uptake inhibits leptin production and signaling in
      adipose tissue.
AB  - Leptin plays an important role in regulating energy expenditure in response to
      food intake, but nutrient regulation of leptin is incompletely understood. In
      this study using in vivo and in vitro approaches, we examined the role of fatty
      acid uptake in modulating leptin expression and production. Leptin levels are
      doubled in the CD36-null mouse, which has impaired cellular fatty acid uptake
      despite a 40% decrease in fat mass. The CD36-null mouse is protected from diet
      induced weight gain but not from that consequent to leptin deficiency. Leptin
      secretion in the CD36-null mouse is strongly responsive to glucose intake,
      whereas a blunted response is observed in the wild-type mouse. This indicates
      that leptin regulation integrates opposing influences from glucose and fatty acid
      and loss of fatty acid inhibition allows unsuppressed stimulation by
      glucose/insulin. Fatty acid inhibition of basal and insulin-stimulated leptin
      release is linked to CD36-facilitated fatty acid flux, which is important for
      fatty acid activation of peroxisome proliferator-activated receptor gamma and
      likely contributes to the nutrient sensing function of adipocytes. Fatty acid
      uptake also may modulate adipocyte leptin signaling. The ratio of phosphorylated
      to unphosphorylated signal transducer and activator of transcription 3, an index
      of leptin activity, is increased in CD36-null fat tissue disproportionately to
      leptin levels. In addition, expression of leptin-sensitive fatty acid oxidative
      enzymes is enhanced. Targeting adipocyte CD36 may offer a way to uncouple leptin
      production and adiposity.

PMID- 17440174
TI  - Tissue-specific effects of rosiglitazone and exercise in the treatment of lipid
      induced insulin resistance.
AB  - Both pharmacological intervention (i.e., thiazolidinediones [TZDs]) and lifestyle
      modification (i.e., exercise training) are clinically effective treatments for
      improving whole-body insulin sensitivity. However, the mechanism(s) by which
      these therapies reverse lipid-induced insulin resistance in skeletal muscle is
      unclear. We determined the effects of 4 weeks of rosiglitazone treatment and
      exercise training and their combined actions (rosiglitazone treatment and
      exercise training) on lipid and glucose metabolism in high-fat-fed rats. High-fat
      feeding resulted in decreased muscle insulin sensitivity, which was associated
      with increased rates of palmitate uptake and the accumulation of the fatty acid
      metabolites ceramide and diacylglycerol. Impairments in lipid metabolism were
      accompanied by defects in the Akt/AS160 signaling pathway. Exercise training, but
      not rosiglitazone treatment, reversed these impairments, resulting in improved
      insulin-stimulated glucose transport and increased rates of fatty acid oxidation
      in skeletal muscle. The improvements to glucose and lipid metabolism observed
      with exercise training were associated with increased AMP-activated protein
      kinase alpha1 activity; increased expression of Akt1, peroxisome proliferator
      activated receptor gamma coactivator 1, and GLUT4; and a decrease in AS160
      expression. In contrast, rosiglitazone treatment exacerbated lipid accumulation
      and decreased insulin-stimulated glucose transport in skeletal muscle. However,
      rosiglitazone, but not exercise training, increased adipose tissue GLUT4 and
      acetyl CoA carboxylase expression. Both exercise training and rosiglitazone
      decreased liver triacylglycerol content. Although both interventions can improve
      whole-body insulin sensitivity, our results show that they produce divergent
      effects on protein expression and triglyceride storage in different tissues.
      Accordingly, exercise training and rosiglitazone may act as complementary
      therapies for the treatment of insulin resistance.

PMID- 17440175
TI  - Organization of the mitochondrial genome in the dinoflagellate Amphidinium
      carterae.
AB  - We have characterized the mitochondrial genome of the dinoflagellate Amphidinium
      carterae. It contains just 3 identifiable protein-coding genes: cox1, cox3, and
      cob. No evidence for rRNA or tRNA genes was found. Expressed sequence tags (EST)
      sequences for the 3 genes suggest that RNA editing occurs in 2 cases removing an
      in-frame stop codon. Two of the transcripts (cob and cox1) lack a stop codon at
      the end of the gene. The genome contains a large amount of noncoding DNA
      including many fragmented copies of all the 3 genes and large numbers of inverted
      repeats. The genome, which contains about 70% AT, has undergone extensive
      recombination, possibly due to the inverted repeats. The highly reduced
      mitochondrial gene content supports the relationship of the dinoflagellates and
      apicomplexa as sister groups.

PMID- 17440176
TI  - Compensatory change of interacting amino acids in the coevolution of
      transcriptional coactivator MBF1 and TATA-box-binding protein.
AB  - To elucidate the transcriptional regulation in eukaryotic genome network, it is
      important to understand coevolution of transcription factors, transcriptional
      coactivators, and TATA-box-binding protein (TBP). In this study, coevolution of
      transcriptional coactivator multiprotein-bridging factor 1 and its interacting
      target TBP was first evaluated experimentally by examining if compensatory amino
      acid changes took place at interacting sites of both proteins. The experiments
      were conducted by identifying interaction sites and comparing the amino acids at
      these sites among different organisms. Here, we provide evidence for compensatory
      changes of transcription coactivator and its interacting target, presenting the
      1st report that transcription coactivator may have undergone coevolution with
      TBP.

PMID- 17440177
TI  - An unsuspected cause of chronic diarrhoea.

PMID- 17440178
TI  - Pathogenesis of gastrinomas associated with multiple endocrine neoplasia type 1.

PMID- 17440179
TI  - Avoiding unnecessary surgery in irritable bowel syndrome.

PMID- 17440180
TI  - The role of Escherichia coli in inflammatory bowel disease.

PMID- 17440181
TI  - Iron, haemochromatosis and thalassaemia as risk factors for fibrosis in hepatitis
      C virus infection.

PMID- 17440182
TI  - An acute left-sided hydrothorax.

PMID- 17440185
TI  - Familial liver disease.

PMID- 17440183
TI  - Irritable bowel syndrome and negative appendectomy: a prospective multivariable
      investigation.
AB  - OBJECTIVE: To examine prospectively whether irritable bowel syndrome (IBS) or
      other variables-that is, psychiatric profiles, health-related quality of life
      (HRQoL) and clinical features-are associated with negative appendectomy (NA).
      DESIGN: Longitudinal study. SETTING: Inpatient and emergency service in a
      university-affiliated teaching hospital. PATIENTS: 430 consecutive patients
      underwent emergent surgery for suspected appendicitis. MAIN OUTCOME MEASURES:
      Rome-II IBS questionnaire; the Hospital Anxiety and Depression Scale; the Short
      Form 36 survey; the clinical, pathological and CT findings. RESULTS: The NA group
      (n = 68, 15.8%) was younger, with female predominance, higher prevalence of Rome
      II IBS, higher anxiety/depression scores and lower levels of HRQoL than the
      positive appendectomy group. The patients with NA tended to have atypical
      presentations (absence of migration pain/fever/muscle guarding), lower white cell
      count and percentage of polymorphonuclear cells (PMNC) and lower rate of CT scan
      usage than the positive group. After multiple logistic regression, IBS (OR 2.17;
      95% CI 1.14 to 4.24), degree of anxiety (OR 1.12; 95% CI 1.02 to 1.49), absence
      of migrating pain (OR 3.43; 95% CI 1.90 to 5.95)/muscle guarding (OR 3.72; 95% CI
      2.07 to 6.70), a lower PMNC percentage (<75%; OR 3.05; 95% CI 1.69 to 5.51) and
      no CT scan usage (OR 2.32; 95% CI 1.27 to 4.26) were found to be the independent
      factors in predicting NA. CONCLUSION: Both patient (IBS, anxiety, atypical
      presentation) and physician (low CT scan usage) factors are the independent
      determinants predicting NA. Physicians should be cautious before operating on or
      referring patients with IBS for appendectomy. CT scan should be considered in
      patients with suspected appendicitis, particularly in those with IBS and atypical
      clinical presentations.

PMID- 17440189
TI  - Mechanical lithotripsy for Bouveret's syndrome.

PMID- 17440187
TI  - Risks and benefits of biologic therapy for inflammatory bowel diseases.

PMID- 17440190
TI  - The role of the selective serotonin reuptake inhibitor citalopram in irritable
      bowel syndrome.

PMID- 17440191
TI  - Bevacizumab and postponed suture leakages after surgery for ulcerative colitis
      and rectal cancer.

PMID- 17440192
TI  - Fertility and ileal pouch-anal anastomosis.

PMID- 17440193
TI  - The incidence and risks of liver biopsy in non-cirrhotic patients: An evaluation
      of 3806 biopsies.

PMID- 17440194
TI  - Role of RET and PHOX2B gene polymorphisms in risk of Hirschsprung's disease in
      Chinese population.

PMID- 17440195
TI  - The role of gender on clearance of hepatitis C virus: a different story in an
      area endemic for hepatitis B and C.

PMID- 17440196
TI  - Relation between incidence of hepatic carcinogenesis and integration value of
      alanine aminotransferase in patients with hepatitis C virus infection.

PMID- 17440197
TI  - Reliability of navigated knee stability examination: a cadaveric evaluation.
AB  - BACKGROUND: Clinical examination remains empirical and may be confusing in the
      setting of rotatory knee instabilities. Computerized navigation systems provide
      the ability to visualize and quantify coupled knee motions during knee stability
      examination. HYPOTHESIS: An image-free navigation system can reliably register
      and collect multiplanar knee kinematics during knee stability examination. STUDY
      DESIGN: Controlled laboratory study. METHODS: Coupled knee motions were
      determined by a robotic/UFS testing system and by an image-free navigation system
      in 6 cadaveric knees that were subjected to (1) isolated varus stress and (2)
      combined varus and external rotation force at 0 degrees, 30 degrees, and 60
      degrees. This protocol was performed in intact knees and after complete
      sectioning of the posterolateral corner (lateral collateral ligament, popliteus
      tendon, and popliteofibular ligament). The correlation between data from the
      surgical navigation system and the robotic positional sensor was assessed using
      the intraclass correlation coefficient. The 3-dimensional motion paths of the
      intact and sectioned knees were assessed qualitatively using the navigation
      display system. RESULTS: Intraclass correlation coefficients between the robotic
      sensor and the navigation system for varus and external rotation at 0 degrees, 30
      degrees, and 60 degrees were all statistically significant at P < .01. The
      overall intraclass correlation coefficient for all tests was 0.9976 (P < .0001).
      Real-time visualization of the coupled motions was possible with the navigation
      system. Post hoc analysis of the knee motion paths during loading distinguished
      distinct rotatory patterns. CONCLUSION: Surgical navigation is a precise
      intraoperative tool to quantify knee stability examination and may help delineate
      pathologic multiplanar or coupled knee motions, particularly in the setting of
      complex rotatory instability patterns. Repeatability of load application during
      clinical stability testing remains problematic. CLINICAL RELEVANCE: Surgical
      navigation may refine the diagnostic evaluation of knee instability.

PMID- 17440199
TI  - Beyond the banality of evil: three dynamics of an interactionist social
      psychology of tyranny.
AB  - Carnahan and McFarland critique the situationist account of the Stanford prison
      experiment by arguing that understanding extreme action requires consideration of
      individual characteristics and the interaction between person and situation.
      Haslam and Reicher develop this argument in two ways. First, they reappraise
      historical and psychological evidence that supports the broader "banality of
      evil" thesis-the idea that ordinary people commit atrocities without awareness,
      care, or choice. Counter to this thesis, they show that perpetrators act
      thoughtfully, creatively, and with conviction. Second, drawing from this evidence
      and the BBC [British Broadcasting Corporation] Prison Study, they make the case
      for an interactionist approach to tyranny that explains how people are (a)
      initially drawn to extreme and oppressive groups, (b) transformed by membership
      in those groups, and (c) able to gain influence over others and hence normalize
      oppression. These dynamics can make evil appear banal but are far from banal
      themselves.

PMID- 17440198
TI  - Preliminary findings for two new measures of social and role functioning in the
      prodromal phase of schizophrenia.
AB  - INTRODUCTION: Research on prediction and prevention of schizophrenia has
      increasingly focused on prodromal (prepsychosis) social and role dysfunction as
      developmentally early, stable, and treatment-resistant illness components. In
      this report, 2 new measures, Global Functioning: Social and Global Functioning:
      Role, are presented, along with preliminary findings about psychometric
      properties and course of social and role (academic/work) functioning in the
      prodromal phase of psychosis. METHODS: Subjects included 69 participants from the
      Recognition and Prevention program and 52 from the Center for the Assessment and
      Prevention of Prodromal States. Ages ranged from 12 to 29 years, and all met
      criteria for Attenuated Positive Symptom syndrome. Retrospective (past year) and
      baseline data are reported for all 121 prodromal subjects and for 44 normal
      controls (NCs). Prospective follow-up data are reported for a subsample of
      patients reevaluated at both 6 and 12 months (N = 44). RESULTS: For both scales,
      interrater reliability was high, and preliminary data supported construct
      validity. Relative to NCs, prodromal individuals displayed impaired social and
      role functioning at baseline. Analyses of change over time indicated that role
      functioning declined over the year before ascertainment and improved over 12
      month follow-up, presumably with treatment. Social impairment, by contrast, was
      constant across time and predicted later psychosis (P = .002). DISCUSSION: Using
      2 new global measures, social functioning was found to be a stable trait,
      unchanged by treatment, with considerable potential to be a marker of
      schizophrenia. Role functioning, by contrast, may be a more direct barometer of
      clinical change and may be responsive to treatment and environmental change.

PMID- 17440200
TI  - Individual differences in analytic versus holistic thinking.
AB  - The authors constructed the Analysis-Holism Scale (AHS) to measure analytic
      versus holistic thinking tendency. In Study 1, using exploratory and confirmatory
      factor analysis, a 24-item scale was developed. In Study 2, convergent and
      discriminant validities were tested. In Studies 3 and 4, the known-group
      difference validity was examined by comparing scores on the AHS of Americans and
      Koreans (Study 3) and of Korean students of Oriental medicine and Korean students
      of non-Oriental medicine majors (Study 4). Results of Studies 3 and 4 show that
      Koreans and Korean students of Oriental medicine scored higher on the AHS than
      did Americans and Korean students of non-Oriental medicine majors, respectively.
      Studies 5 and 6 tested predictive validity by examining associations of the AHS
      with performances on two cognitive tasks (categorization and causal reasoning).
      Data analysis shows that those with high scores on the AHS displayed the holistic
      pattern of performances on each task more than did those with low scores.

PMID- 17440201
TI  - On the self-regulation of implicit and explicit prejudice: a self -determination
      theory perspective.
AB  - The present study identifies a broad taxonomy of motives underlying the desire to
      regulate prejudice and assess the impact of motivation to regulate prejudice on
      levels of explicit and implicit prejudice. Using self-determination theory as the
      foundation, six forms of motivation to regulate prejudice are proposed. In Study
      1 (N = 257), an exploratory factor analysis reveals evidence for the six proposed
      dimensions. In Study 2 (N = 198), the six-factor taxonomy of motivation to
      regulate prejudice is further validated using a confirmatory factor analysis, and
      construct validity is obtained. In Study 3 (N = 62), motivation to regulate
      prejudice is manipulated before participants complete the Implicit Association
      Test (IAT) and explicit measures of prejudice. Results reveal that those with
      highly self-determined regulation of prejudice demonstrate lower implicit and
      explicit prejudice than their less self-determined counterparts. Results are
      discussed in terms of an increased understanding of the motivation to control
      prejudice.

PMID- 17440202
TI  - Those speedos become them: the role of self-objectification in gay and
      heterosexual men's body image.
AB  - Objectification Theory proposes that membership in sexually objectifying Western
      societies gradually socializes women to adopt an observer's perspective on their
      physical self. This leads to negative consequences, including body shame and
      restricted eating behavior. The authors extend this framework to investigate a
      subgroup of men, namely gay men, who also exist in a subculture that emphasizes
      and values physical appearance. Study 1 investigated trait differences in self
      objectification and body image among gay and heterosexual men. Analyses indicated
      that gay men scored higher on self-objectification, body shame, body
      dissatisfaction, and drive for thinness. In Study 2, the authors experimentally
      manipulated state self-objectification and found that for gay men, increasing
      state self-objectification resulted in greater body shame and dissatisfaction and
      more restrained eating. Together, these results offer strong support to
      Objectification Theory as a useful framework from within which to view the
      experience of gay men.

PMID- 17440203
TI  - Are effects of emotion expression on trait impressions mediated by babyfaceness?
      Evidence from connectionist modeling.
AB  - Two studies provided evidence that bolsters the Marsh, Adams, and Kleck
      hypothesis that the morphology of certain emotion expressions reflects an evolved
      adaptation to mimic babies or mature adults. Study 1 found differences in emotion
      expressions' resemblance to babies using objective indices of babyfaceness
      provided by connectionist models that are impervious to overlapping cultural
      stereotypes about babies and the emotions. Study 2 not only replicated parallels
      between impressions of certain emotions and babies versus adults but also showed
      that objective indices of babyfaceness partially mediated impressions of the
      emotion expressions. babyface effects were independent of strong effects of
      attractiveness, and babyfaceness did not mediate impressions of happy
      expressions, to which the evolutionary hypothesis would not apply.

PMID- 17440204
TI  - When prosocials act like proselfs in a commons dilemma.
AB  - Past research has shown that people with prosocial orientations exercise
      restraint when collectively shared resources are close to being depleted, whereas
      people with proself orientations tend to maintain high levels of consumption.
      This research seeks to extend this important finding by examining whether the
      presence of noise in social-ecological interaction may modify the effects of
      social values in a commons dilemma. Participants were taking resources from a
      gradually declining pool. For half of the participants, the intended consumption
      was subject to incidental increases in consumption (negative noise). Consistent
      with hypotheses, noise exerted detrimental effects on cooperation when resources
      became scarce, yet these effects were only observed for prosocials, not for
      proselfs. These results indicate that noise in social-ecological interaction
      plays an important role in common-pool management. It tends to undermine
      cooperation among those who are otherwise inclined to save resources.

PMID- 17440205
TI  - Thinking straight while seeing red: the influence of anger on information
      processing.
AB  - Because angry people apparently rely on heuristic cues when making judgments,
      anger has been claimed to trigger superficial, nonanalytic information
      processing. In three studies, the authors found that induced anger promoted
      analytic processing. Experiment 1 showed that angry participants were more likely
      to discriminate between weak and strong arguments than participants in neutral
      moods. Experiment 2 demonstrated that anger overrode dispositional preferences
      not to process, causing even those low in need for cognition to process
      analytically. Experiment 3 reconciled these findings with previous work by
      showing that angry people used accessible, valid, and relevant heuristics but
      otherwise processed analytically, as indicated by attitude change and elaboration
      data. Together, these experiments showed that angry people can have both the
      capacity and motivation to process and that their selective use of heuristics
      reflects the cue's perceived validity and not the failure to process
      analytically.

PMID- 17440206
TI  - Interfering with inferential, but not associative, processes underlying
      spontaneous trait inference.
AB  - Three studies explore mental processes underlying spontaneous trait inferences
      about self-informants and the spontaneous trait transference characterizing third
      party informants. Process differences are suggested in that instructions
      prompting a nontrait inference (truth or lie?) reduce self-informant trait
      savings effects and lower self-informant trait judgments. For third-party
      informants, such instructions have no effect on these outcome variables. Results
      of a third study are inconsistent with cognitive load as an explanation for these
      effects. Taken together, these results indicate that inferences, and not merely
      associations, spontaneously form when processing information about self
      informants. The results also show that the inferences and judgments that occur in
      spontaneous trait transference are not caused by the misidentification of third
      party informants as self-informants.

PMID- 17440207
TI  - Laying it on thin: analogical cue frequency in the manipulation of choice.
AB  - Persuasive analogies consist of linguistic cues that invite audiences to
      represent a problem in terms of an analog and to make choices compatible with
      this manipulated representation. The authors explore how the frequency of
      linguistic cues moderates analogical bias in choice behavior. Participants read
      versions of a managerial decision scenario differing in the number of sports
      (e.g., game plan) or family (e.g., parent company) idioms used to describe
      situational attributes and then chose between analogically consistent and
      inconsistent response options. Analogies consisting of an intermediate number of
      cues elicited higher rates of analogically consistent responding than those of
      higher and lower cue frequency. When explaining their responses, participants
      referred to the sports or family analogies most often to rationalize rejecting
      the analogically consistent response option after reading high cue frequency
      versions. These findings indicate that there are lower and upper boundaries to a
      persuasive analogy's optimal cue frequency.

PMID- 17440208
TI  - Mindfulness and the intention-behavior relationship within the theory of planned
      behavior.
AB  - The present study examined moderating effects of mindfulness on the intention
      behavior relationship within the theory of planned behavior. Mindfulness
      describes a quality of consciousness characterized by heightened clarity and
      awareness of present experiences and functioning. Study 1 showed that mindfulness
      moderated the intention-behavior relationship in a leisure-time physical activity
      context such that intentions predicted physical activity among mindful
      individuals and not among less-mindful individuals. Study 2 measured
      counterintentional habits relating to binge-drinking and found that habitual
      binge-drinking obstructed the enactment of physical activity intentions among
      individuals acting less mindfully but not among individuals acting mindfully.
      Finally, Studies 1 and 2 demonstrated that the effects of mindfulness on physical
      activity were independent of effects observed for habit and variables contained
      in the theory of planned behavior. These findings suggest that mindfulness is a
      useful construct that helps understand the intention-behavior relationship within
      the theory of planned behavior.

PMID- 17440209
TI  - Goal-discrepant situations prime goal-directed actions if goals are temporarily
      or chronically accessible.
AB  - This research tested the hypothesis that perception of goal-discrepant situations
      automatically (i.e., without conscious intent) facilitates access to
      representations of instrumental actions if goal representations are mentally
      accessible. Employing a probe-recognition paradigm, Experiment 1 established that
      sentences describing situations that are discrepant with the goal of "looking
      well-groomed" (e.g., having dirty shoes) automatically increased the
      accessibility of representations of appropriate instrumental actions (e.g.,
      polishing) in comparison to control situations, but only when participants
      frequently pursued the goal. Experiments 2a and 2b suggest that this effect was
      due to chronic accessibility of the goal representation and demonstrate that the
      same effects occur if the accessibility of the goal is temporarily enhanced (by
      subliminal priming) for people that nonfrequently pursue the goal.

PMID- 17440210
TI  - Revisiting the Stanford prison experiment: could participant self-selection have
      led to the cruelty?
AB  - The authors investigated whether students who selectively volunteer for a study
      of prison life possess dispositions associated with behaving abusively. Students
      were recruited for a psychological study of prison life using a virtually
      identical newspaper ad as used in the Stanford Prison Experiment (SPE; Haney,
      Banks & Zimbardo, 1973) or for a psychological study, an identical ad minus the
      words of prison life. Volunteers for the prison study scored significantly higher
      on measures of the abuse-related dispositions of aggressiveness,
      authoritarianism, Machiavellianism, narcissism, and social dominance and lower on
      empathy and altruism, two qualities inversely related to aggressive abuse.
      Although implications for the SPE remain a matter of conjecture, an
      interpretation in terms of person-situation interactionism rather than a strict
      situationist account is indicated by these findings. Implications for
      interpreting the abusiveness of American military guards at Abu Ghraib Prison
      also are discussed.

PMID- 17440211
TI  - On mathematical modeling of circadian rhythms, performance, and alertness.
AB  - Mathematical models of neurobehavioral performance and alertness have both basic
      science and practical applications. These models can be especially useful in
      predicting the effect of different sleep-wake schedules on human neurobehavioral
      objective performance and subjective alertness under many conditions. Several
      relevant models currently exist in the literature. In principle, the development
      and refinement of any mathematical model should be based on an explicit modeling
      methodology, such as the Box modeling paradigm, that formally defines the model
      structure and calculates the set of parameters. While most mathematical models of
      neurobehavioral performance and alertness include homeostatic, circadian, and
      sleep inertia components and their interactions, there may be fundamental
      differences in the equations included in these models. In part, these may be due
      to differences in the assumptions of the underlying physiology. Because the
      choice of model equations can have a dramatic influence on the results, it is
      necessary to consider these differences in assumptions when examining the results
      from a model and when comparing results across models. This article presents
      principles of mathematical modeling and examples of how such procedures can be
      applied to the development and refinement of mathematical models of
      neurobehavioral performance and alertness. This article also presents several
      methods of testing and comparing these models, suggests different uses of the
      models, and discusses problems with current models.

PMID- 17440212
TI  - Induction of Drosophila behavioral and molecular circadian rhythms by temperature
      steps in constant light.
AB  - In constant light, where Drosophila rhythms are normally disrupted, temperature
      cycles induce circadian rhythms at both the molecular and behavioral level. The
      authors investigated the process by which the thermoperiod induces the rhythms
      using temperature steps. A 10 degrees C temperature step-up induced a single
      locomotor activity peak ca 9 h after the temperature transition, whereas a 10
      degrees C step-down induced a strong activity peak ca 24 h after the transition,
      and the peak recurred for several cycles, suggesting that the underlying clock is
      reset. Arrhythmic per(01) , tim( 01) , dClk(Jrk) , and cyc(01) mutant flies
      failed to show the rhythm after the step-down, suggesting that per, tim, dClk,
      and cyc are necessary for the step-down-induced rhythm. After the step-up,
      per(01) flies exhibited an activity peak similar to that of wild-type flies,
      suggesting that the peak can be induced by the step-up in absence of PER. mRNA
      levels of per, tim , dClk, vri, and Pdp1epsilon were changed in response to the
      temperature steps, but the changes differed depending on the direction of
      temperature steps, suggesting that steps-up and steps-down have different roles
      in the initiation of the oscillation. Probably, alternating 12-h temperature
      steps-up and steps-down will induce opposite changes in mRNA levels of clock
      genes, eventually producing stable molecular oscillations. Although TIM shows
      responses to temperature consistent with the changes of its mRNA, this is not the
      case for PER, consistent with posttranscriptional regulation. Changes of the mRNA
      levels were significantly altered but still observed in per( 01) flies but not
      observed in dClk(Jrk) flies, except for per mRNA. This suggests that dCLK is
      involved in the temperature-induced changes in the levels of most clock gene mRNA
      but that per is regulated via a different mechanism.

PMID- 17440213
TI  - Separate sets of cerebral clock neurons are responsible for light and temperature
      entrainment of Drosophila circadian locomotor rhythms.
AB  - The fruit fly Drosophila melanogaster shows a bimodal circadian locomotor rhythm
      with peaks at lights-on and before lights-off, which are regulated by multiple
      clocks in the brain. Even under light-dark cycles, the timing of the evening peak
      is highly dependent on temperature, starting earlier under lower ambient
      temperature but terminating almost at the same time. In the present study, using
      behavioral and immunohistochemical assays, the authors show that separate groups
      of clock neurons, either light-entrainable or temperature-entrainable, form a
      functional system driving the locomotor rhythm. When subjected to a light cycle
      combined with a temperature cycle advanced by 6 h relative to the light cycle,
      the dorsally located neurons (DNs) and lateral posterior neurons (LPNs) shifted
      their phase of TIMELESS expression, but the laterally located protocerebral
      neurons (LNs) basically maintained their original phase. Thus, the LNs seem to be
      preferentially light-entrainable and the DNs and LPNs to be primarily temperature
      entrainable. In pdf(01) mutant flies that lack the neuropeptide PDF in the
      ventral groups of LNs, the onset of the evening peak was greatly advanced even
      under synchronized light and temperature cycles and was shifted even more than in
      wild-type flies in response to a 6-h phase shift of the temperature cycle,
      suggesting that ventral LNs have a strong impact on the phase of the other cells.
      It seems likely that the 2 sets of clock cells with different entrainability to
      light and temperature, and the coupling between them, enable Drosophila to keep a
      proper phase relationship of circadian activity with respect to the daily light
      and temperature cycles.

PMID- 17440214
TI  - Light-inducible and clock-controlled expression of MAP kinase phosphatase 1 in
      mouse central pacemaker neurons.
AB  - MAP kinase phosphatase 1 (MKP1) is a negative regulator for the mitogen-activated
      protein kinase (MAPK)-mediated signal transduction, a key pathway that leads to
      the regulated expression of circadian clock genes. Here the authors analyzed mkp1
      expression by in situ hybridization and found that mkp1 is a light-inducible and
      clock-controlled gene expressed in the central pacemaker neurons of the
      hypothalamic SCN. Interestingly, mkp1 presents a marked similarity to the clock
      core gene per1 in terms of the gene expression profiles as well as the gene
      promoter organization. Both mkp1 and per1 are subject to bimodal regulation in
      the SCN: the external light-dependent acute up-regulation and the functional
      clock-dependent circadian oscillation. Consistent with this, the authors show
      that mkp1 gene has a per1-like promoter that contains 2 functionally distinct
      elements: cAMP-responsive element (CRE) and E-box. CRE sites present in the mkp1
      promoter constitute the functional binding sites for the CRE binding protein
      (CREB), which serves as an important regulator that mediates the light-induced
      signaling cascades in the SCN neurons. Furthermore, the authors show that the E
      box present in the mkp1 promoter is necessary and sufficient for transcriptional
      control exerted by circadian clock core regulators that include a positive
      complex CLOCK/BMAL1 and a negative factor CRY1. The authors' studies on mkp1 have
      identified for the first time a gene encoding a phosphatase that functions in
      light-dependent and time-of-day-dependent manners in the mammalian central clock
      structure SCN.

PMID- 17440216
TI  - Daily light exposure in morning-type and evening-type individuals.
AB  - Morning-type individuals (M-types) have earlier sleep schedules than do evening
      types (E-types) and therefore differ in their exposure to the external light-dark
      cycle. M-types and E-types usually differ in their endogenous circadian phase as
      well, but whether this is the cause or the consequence of the difference in light
      exposure remains controversial. In this study, ambulatory monitoring was used to
      measure 24-h light exposure in M-type and E-type subjects for 7 consecutive days.
      The circadian phase of each subject was then estimated in the laboratory using
      the dim-light melatonin onset in saliva (DLMO) and the core body temperature
      minimum (Tmin). On average, M-types had earlier sleep schedules and earlier
      circadian phases than E-types. They also showed more minutes of daily bright
      light exposure (> 1000 lux) than E-types. As expected, the 24-h patterns of light
      exposure analyzed in relation to clock time indicated that M-types were exposed
      to more light in the morning than E-types and that the reverse was true in the
      late evening. However, there was no significant difference when the light
      profiles were analyzed in relation to circadian phase, suggesting that, on
      average, the circadian pacemaker of both M-types and E-types was similarly
      entrained to the light-dark cycle they usually experience. Some M-types and E
      types had different sleep schedules but similar circadian phases. These subjects
      also had identical light profiles in relation to their circadian phase. By
      contrast, M-types and E-types with very early or very late circadian phases
      showed large differences in their profiles of light exposure in relation to their
      circadian phase. This observation suggests that in these individuals, early or
      late circadian phases are related to relatively short and long circadian periods
      and that a phase-delaying profile of light exposure in M-types and a phase
      advancing profile in E-types are necessary to ensure a stable entrainment to the
      24-h day.

PMID- 17440215
TI  - Circadian variations in clock gene expression of human bone marrow CD34+ cells.
AB  - Time-dependent variations in clock gene expression have recently been observed in
      mouse hematopoietic cells, but the activity of these genes in human bone marrow
      (BM) has so far not been investigated. Since such data can be of considerable
      clinical interest for monitoring the dynamics in stem/progenitor cells, the
      authors have studied mRNA expression of the clock genes hPer1 , hPer2, hCry1,
      hCry2, hBmal1, hRev-erb alpha, and hClock in human hematopoietic CD34-positive
      (CD34( +)) cells. CD34(+) cells were isolated from the BM samples obtained from
      10 healthy men at 6 times over 24 h. In addition, clock gene mRNA expression was
      analyzed in the whole BM in 3 subjects. Rhythms in serum cortisol, growth
      hormone, testosterone, and leukocyte counts documented that subjects exhibited
      standardized circadian patterns. All 7 clock genes were expressed both in CD34(+)
      cells and the whole BM, with some differences in magnitude between the 2 cell
      populations. A clear circadian rhythm was shown for hPer1, hPer2, and hCry2
      expression in CD34(+) cells and for hPer1 in the whole BM, with maxima from early
      morning to midday. Similar to mouse hematopoietic cells, h Bmal1 was not
      oscillating rhythmically. The study demonstrates that clock gene expression in
      human BM stem/progenitor cells may be developmentally regulated, with strong or
      weaker circadian profiles as compared to those reported in other mature tissues.

PMID- 17440217
TI  - Circadian physiology is a toxicity target of the anticancer drug gemcitabine in
      mice.
AB  - The circadian timing system determines the optimal timing and waveform of drug
      tolerability, yet treatment itself can alter this system. Gemcitabine is an
      antimetabolite agent that is active against lung and pancreatic cancers.
      Tolerability for this drug is best following dosing at ZT 11 in mice. The authors
      investigated the effects of gemcitabine on the circadian rhythms in body
      temperature and rest activity as physiological markers of the circadian timing
      system. Healthy unrestrained B6D2F(1) mice implanted with radiotelemetry
      transmitters were kept in LD 12:12 prior to receiving a single intravenous dose
      of gemcitabine (200, 400, or 600 mg/kg) at ZT 11 or 23. Gemcitabine (400 mg/kg)
      transiently suppressed the body temperature rhythm in 50% of the mice dosed at ZT
      23, as compared to none of the mice treated at ZT 11 within the 2 days following
      drug dosing (Fisher 's exact test p = 0.04). The rest-activity circadian rhythm
      was suppressed in 40% (ZT 11) and 50% (ZT 23) of the mice, respectively. In the
      mice with persistent circadian rhythms, gemcitabine delivery at ZT 23 resulted in
      more prominent decreases and slower recovery of circadian mesor and amplitude of
      both rhythms as compared to mice treated at ZT 11. Gemcitabine also induced a
      transient internal desynchronization between temperature and activity rhythms
      following dosing at ZT 23 but not at ZT 11. The delivery of a single therapeutic
      dose of gemcitabine near its time of least toxicity produced least alterations in
      circadian physiological outputs, a finding that suggests that the extent of
      circadian disruption contributes to toxicokinetic processes.

PMID- 17440218
TI  - A quantitative model of sleep-wake dynamics based on the physiology of the
      brainstem ascending arousal system.
AB  - A quantitative, physiology-based model of the ascending arousal system is
      developed, using continuum neuronal population modeling, which involves averaging
      properties such as firing rates across neurons in each population. The model
      includes the ventrolateral preoptic area (VLPO), where circadian and homeostatic
      drives enter the system, the monoaminergic and cholinergic nuclei of the
      ascending arousal system, and their interconnections. The human sleep-wake cycle
      is governed by the activities of these nuclei, which modulate the behavioral
      state of the brain via diffuse neuromodulatory projections. The model parameters
      are not free since they correspond to physiological observables. Approximate
      parameter bounds are obtained by requiring consistency with physiological and
      behavioral measures, and the model replicates the human sleep-wake cycle, with
      physiologically reasonable voltages and firing rates. Mutual inhibition between
      the wake-promoting monoaminergic group and sleep-promoting VLPO causes ;;flip
      flop'' behavior, with most time spent in 2 stable steady states corresponding to
      wake and sleep, with transitions between them on a timescale of a few minutes.
      The model predicts hysteresis in the sleep-wake cycle, with a region of
      bistability of the wake and sleep states. Reducing the monoaminergic-VLPO mutual
      inhibition results in a smaller hysteresis loop. This makes the model more prone
      to wake-sleep transitions in both directions and makes the states less
      distinguishable, as in narcolepsy. The model behavior is robust across the
      constrained parameter ranges, but with sufficient flexibility to describe a wide
      range of observed phenomena.

PMID- 17440220
TI  - Principles of professional ethics for scientists.

PMID- 17440219
TI  - Phase sensitivity analysis of circadian rhythm entrainment.
AB  - As a biological clock, circadian rhythms evolve to accomplish a stable (robust)
      entrainment to environmental cycles, of which light is the most obvious. The
      mechanism of photic entrainment is not known, but two models of entrainment have
      been proposed based on whether light has a continuous (parametric) or discrete
      (nonparametric) effect on the circadian pacemaker. A novel sensitivity analysis
      is developed to study the circadian entrainment in silico based on a limit cycle
      approach and applied to a model of Drosophila circadian rhythm. The comparative
      analyses of complete and skeleton photoperiods suggest a trade-off between the
      contribution of period modulation (parametric effect) and phase shift
      (nonparametric effect) in Drosophila circadian entrainment. The results also give
      suggestions for an experimental study to (in)validate the two models of
      entrainment.

PMID- 17440221
TI  - Influenza epidemics and acute respiratory disease activity are associated with a
      surge in autopsy-confirmed coronary heart disease death: results from 8 years of
      autopsies in 34,892 subjects.
AB  - AIMS: To determine whether influenza can trigger heart attacks, we investigated
      the impact of influenza epidemics on autopsy-proven coronary deaths. METHODS AND
      RESULTS: We studied weekly death due to acute myocardial infarction (AMI) and
      chronic ischaemic heart disease (IHD) in autopsies conducted in 1993 to 2000 in
      St Petersburg, Russia. We plotted the weekly acute respiratory disease (ARD)
      counts and influenza epidemics against AMI and chronic IHD deaths. There were
      11,892 subjects dying of AMI and 23 000 subjects dying of chronic IHD. Median age
      was 75 for women and 65 for men. In every year, a peak of AMI and chronic IHD
      deaths were present and coincided with the influenza epidemic and peak ARD
      activity. A similar pattern was seen for each subgroup of men, women, subjects 50
      years or older, and subjects 70 years or older. When comparing the average
      influenza epidemic weeks to average off-season weeks, the odds for AMI and
      chronic IHD death increased by 1.30 (95% confidence interval (CI): 1.08-1.56) and
      1.10 (95% CI: 0.97-1.26), respectively. CONCLUSION: Influenza epidemics are
      associated with a rise in autopsy-confirmed coronary deaths. Influenza
      vaccination should be advocated for patients at high risk of developing
      cardiovascular events.

PMID- 17440222
TI  - Intracerebroventricular physostigmine enhances blood pressure and heat loss in
      running rats.
AB  - The aim of this study was to evaluate the effects of the stimulation of central
      cholinergic synapses in the regulation of heat loss in untrained rats during
      exercise. The animals were separated into two groups (exercise or rest) and tail
      skin temperature (T(tail)), core temperature and blood pressure were measured
      after injection of 2 microL of 5x10(-3) M physostigmine (Phy; n = 8) or 0.15 M
      NaCl solution (Sal; n = 8) into the lateral cerebral ventricle. Blood pressure
      was recorded by a catheter implanted into the abdominal aorta, T(tail) was
      measured using a thermistor taped to the tail and intraperitoneal temperature
      (T(b)) was recorded by telemetry. During exercise, Phy-treated rats had a higher
      increase in mean blood pressure (147 +/- 4 mmHg Phy vs. 121 +/- 3 mmHg Sal; P <
      0.001) and higher T(tail) (26.4 +/- 1.0 degrees C Phy vs. 23.8 +/- 0.5 degrees C
      Sal; P < 0.05) that was closely related to the increase in systolic arterial
      pressure (r = 0.83; P < 0.001). In addition, Phy injection attenuated the
      exercise-induced increase in T(b) compared with controls without affecting
      running time. We conclude that the activation of central cholinergic synapses
      during exercise increases heat dissipation due to the higher increase in blood
      pressure.

PMID- 17440223
TI  - Worsening of long-term myocardial function after successful pharmacological
      pretreatment with cyclosporine.
AB  - Pretreatment with cyclosporine (CsA) decreases infarct size 24h after myocardial
      ischemia/reperfusion (I/R). The goal of this study was to determine effects of
      CsA pretreatment on long-term cardiac function after I/R-injury. Rats were
      randomly assigned to group-1: vehicle-only, group-2: CsA-5mg/kg/day, and group-3:
      CsA-12.5mg/kg/day given orally for three days prior to I/R-injury (30 min of left
      anterior descending coronary artery occlusion). Post-I/R survival and cardiac
      function were evaluated 14 days after I/R-injury by echocardiography and invasive
      hemodynamic measurements. Rats with I/R-injury showed increased left ventricular
      pressure (LVEDP) compared to rats without I/R-injury (p<0.005). Although CsA
      initially decreased infarct size, no differences of LVEDP were seen 14 days after
      I/R-injury (vehicle: 21.2+/-8.9 mmHg, CsA-5mg/kg/day: 21.5+/-0.7 mmHg, CsA
      12.5mg/kg/day: 20.5+/-9.4 mmHg). Ejection fraction and fractional shortening were
      decreased compared to baseline, but showed no differences between groups. On day
      14, a dose-dependent increase in left ventricular end diastolic diameter was seen
      (p<0.001). CsA pretreatment was associated with a dose-dependent decrease in post
      I/R-survival (vehicle: 56%, CsA-5mg/kg/day: 32%, CsA-12.5mg/kg/day: 16%;
      p=0.017). CsA pretreatment did not improve long-term cardiac function despite
      decreased infarct size 24h after I/R-injury, but increased post-I/R mortality
      significantly. Poor cardiac function after CsA pretreatment might be caused by
      left ventricular dilation.

PMID- 17440224
TI  - Long-term effects of early administered sildenafil and NO donor on the
      cardiovascular system of SHR.
AB  - We evaluated the long-term effect of NO-donor, pentaerythrityl tetranitrate
      (Petn), and sildenafil citrate (sildenafil) on the cardiovascular system of the
      spontaneously hypertensive rat (SHR). Petn (100 mg/kg/day) and sildenafil (10
      mg/kg/day) were administered to SHR individually or together from week 4 (pre
      hypertensive period) to week 9 of age. Blood pressure (BP) was measured using a
      plethysmographic method. The animals were perfused with a glutaraldehyde fixative
      (120 mmHg). Carotid (AC) and coronary artery (RS) were processed according to
      electron microscopy procedure. Geometry of the arteries was measured on semi-thin
      sections using light microscopy. Administration of Petn and sildenafil to SHR
      individually or together did not prevent an increase of BP, but evoked a decrease
      of cardiac hypertrophy. Petn and sildenafil affected the geometry of RS and AC
      differently. In the RS, an increase of inner diameter (ID) without an increase of
      wall thickness (WT) resulted in increased WT/ID and circumferential stress. In
      the AC, changes in ID were accompanied by changes in WT and, thereby, WT/ID and
      circumferential stress remained unchanged. The arterial wall mass of both
      arteries was increased. The data suggest that administration of the NO donor,
      Petn, and/or sildenafil does not result in a beneficial effect on the myocardium
      or on the geometry of the carotid and coronary arteries.

PMID- 17440225
TI  - Nitric oxide-mediated nonadrenergic noncholinergic relaxation of piglet pulmonary
      arteries decreases with postnatal age.
AB  - Nonadrenergic noncholinergic (NANC) vasodilator mechanisms may contribute to the
      maintenance of adult pulmonary and systemic vascular tone. However, their actions
      in the neonatal circulation have not been studied. We aimed to investigate NANC
      vasorelaxation in neonatal and 2-week-old piglet pulmonary and mesenteric
      arteries and to examine the potential role of nitric oxide (NO) in this
      phenomenon. Responses to electric field stimulation (EFS, 50V, 0.25-32 Hz) were
      investigated in pulmonary and mesenteric artery rings (external diameter 150-200
      microm) precontracted with the thromboxane A2 mimetic U46619, in the presence of
      guanethidine (10 microM) and atropine (10 microM). Under these conditions, EFS
      resulted in a frequency dependent relaxation of newborn pulmonary (maximal
      relaxation of 53+/-9.1%), mesenteric (68.8.2+/-7.1%) and 2-wk-old mesenteric (46
      6.3%) arteries but this relaxation was significantly reduced (4.5+/-2.2%) in 2
      week-old pulmonary arteries. In neonatal pulmonary arteries, the neurotoxin
      tetrodotoxin (0.3 muM), the NO synthase inhibitor L-NAME (0.1 mM), and the
      guanylyl cyclase inhibitor ODQ (10 microM) abolished EFS-induced relaxations,
      suggesting that NANC relaxation of porcine neonatal pulmonary arteries is
      mediated by NO, which is probably neuronal in origin. However, The expression in
      pulmonary arteries of the neuronal NO synthase (nNOS), as determined by Western
      blot analysis, increased with postnatal age whereas the expression of the
      endothelial NOS (eNOS) did not change. In conclusion, NANC relaxation is present
      in neonatal pulmonary and mesenteric arteries and it is, at least partially,
      mediated through NO. NANC relaxation of porcine pulmonary and mesenteric arteries
      decreases with postnatal maturation.

PMID- 17440226
TI  - PPARalpha agonist induces the accumulation of ceramide in the heart of rats fed
      high-fat diet.
AB  - It was shown that high-fat feeding of mice with cardiac-specific overexpression
      of peroxisome proliferator-activated receptor (PPAR) alpha but not wild type
      animals leads to the accumulation of ceramide (an important mediator of
      lipotoxicity) in the heart [Finck et al. 2003 Proc Natl Acad Sci USA]. To
      investigate the mechanism of this phenomenon we examined the effects of PPARalpha
      activation on ceramide metabolism in the myocardium. Male Wistar rats were fed
      either a standard chow or a high-fat diet. Each group was divided into two
      subgroups: control and treated with selective PPARalpha activator - WY-14643. In
      the rats fed on the standard diet WY-14643 did not affect the myocardial content
      of sphingomyelin and ceramide but reduced the content of sphinganine and
      sphingosine. It also inhibited the activity of neutral sphingomyelinase and
      increased the activity of acid sphingomyelinase, whereas the activity of
      ceramidases and serine palmitoyltransferase (SPT) remained stable. High-fat diet
      itself did not affect the content of the examined sphingolipids. However, it
      reduced the activity of sphingomyelinases and ceramidases having no effect on the
      activity of SPT. Administration of WY-14643 to this group significantly increased
      the content of myocardial free palmitate, ceramide, sphingomyelin and the
      activity of SPT. Our results demonstrated that PPARalpha activation modulates
      myocardial ceramide metabolism and leads to the accumulation of ceramide in the
      heart of the high-fat fed rats due to its increased synthesis de novo.

PMID- 17440227
TI  - Effect of IL-6 deficiency on myocardial expression of fatty acid transporters and
      intracellular lipid deposits.
AB  - IL-6 is a biologically active substance and is thought to contribute to the
      development of obesity. Recent findings suggest that susceptibility to
      intracellular lipid accumulation is to a large extent determined by changes in
      the expression of fatty acid transporters such as FAT/CD36, FABPpm and FATP-1.
      The aim of the present study was to determine the effect of IL-6 deficiency on
      the expression of fatty acid transporters, as well as, assess the concomitant
      changes in intracellular lipids. We found that Il-6 deficiency upregulated the
      myocardial expression of FAT/CD36 (+40%) and did not significantly affect the
      content of FABPpm and FATP-1 (+15% and +5% respectively). Although no change in
      the intramyocardial total lipid content was noted, there was a significant
      increase in the intracellular content of both free fatty acid (FFA),
      diacylglicerol (DG) and ceramide fractions (+45%, +37% and +48%, respectively) in
      hearts from IL-6 -/- mice. A trend for IL-6 deficiency to increase in saturated
      FA species in these fractions was also observed (+8%, +12% and +10%,
      respectively). In contrast, IL-6 deficiency has no effect on the content of
      monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) species
      in each intramyocardial lipid fractions examined. These findings suggest that IL
      6 deficiency results in 1) upregulation of myocardial content of FAT/CD36, 2) the
      increase in the content of biologically active lipid pools (FFA, DG and
      ceramide). This lipid accumulation with concomitant trend for increase in the
      saturation status of these lipid fractions may, at least in part, provide a
      factor related to the development of intramyocardial lipotoxicity, observed in
      obese individuals.

PMID- 17440228
TI  - Effects of two types of restraint stress on spontaneous behavior of Sprague
      Dawley and Lewis rats.
AB  - The purpose of this study was to evaluate the action of two types of stressors in
      Sprague-Dawley (S-D) and Lewis (LEW) rats differing in their hypothalamic
      pituitary-adrenal axis activity on locomotion and rearing in an open space.
      Exposure to restraint immobilization alone (IMO) or this immobilization combined
      with cold water (22 degrees C) immersion (IMO+C) lasted for 1 h and started 2 or
      5 h before the test. To evaluate the acute and persisting effects of both
      stressors, four trials were performed in one-week intervals; rats were exposed to
      the stressors in trial 1 and 3. While in LEW rats both acute stressors produced
      reduction of locomotion and rearing in all stressed groups, S-D rats responded
      with a decrease of both parameters only after IMO+C presented 2 h before testing.
      Neither strain displayed a changed performance one week after the first stress
      exposure. One week after the second stress exposure rats of both strains
      exhibited a tendency to an increase of both parameters reaching the significance
      in several experimental groups. The findings indicate: a) the IMO+C produced
      stronger behavioral alteration than IMO alone; b) the behavioral responses to
      stressors were more pronounced in LEW compared to S-D strain; c) change from the
      reduction of activity to its increase may be interpreted as bi-directional
      manifestation of long-term effects of immobilization stress.

PMID- 17440229
TI  - Postural changes associated with public speech tests lead to mild and selective
      activation of stress hormone release.
AB  - We tested whether simulation of postural changes, which occur during public
      speech test procedures, activates cardiovascular system and stress hormone
      release that could interfere with the effect of psychosocial stress load. Young
      healthy male volunteers (n=8) underwent procedure imitating exactly all postural
      changes present in the psychosocial stress model based on public speech used in
      this laboratory (namely changes from sitting to standing and repeated sitting).
      Postural changes were associated with increases in heart rate, blood pressure,
      plasma concentrations of noradrenaline and aldosterone and elevation in plasma
      renin activity. In contrast to cardiovascular parameters, adrenocorticotropic
      hormone, cortisol and adrenaline, the main characteristics of hormonal response
      during mental stress, were not significantly influenced. The overall magnitude of
      all observed alterations was much smaller than that seen following mental stress
      procedures in our previous studies. This study provides evidence that changes in
      body posture during public speech test procedure influence hemodynamics and
      endocrine responses in a mild manner. Though this influence may represent a
      source of unspecific variance, substantial confounding effects on responses to
      the psychosocial component of the procedure are unlikely. In any case, models
      combining mental stressors and changes in body posture must be interpreted as
      complex stress stimuli.

PMID- 17440230
TI  - The role of prednisolone and epinephrine on gastric tissue and erythrocyte
      antioxidant status in adrenalectomized rats.
AB  - It has been believed that overproduction of free radicals and/or deficiency of
      antioxidant systems, and stress hormones may play a role in etiopathogenesis of
      many diseases, including gastric ulcer. This study evaluated whether there was an
      effect of adrenalectomy on lipid peroxidation [malondialdehyde (MDA)] and
      antioxidant [superoxide dismutase (SOD), glutathione peroxidase (GPX) and
      glutathione (GSH) levels] systems in gastric tissue and erythrocyte in rats. As
      well, the impacts of administration of prednisolone and epinephrine on these
      systems in adrenalectomized rats were investigated. Thirty-three rats were
      randomly grouped as sham-operated (group I), adrenalectomized (group II),
      adrenalectomized + prednisolone (group III) and adrenalectomized + epinephrine
      (group IV). After experimental procedures, blood and gastric tissues samples were
      taken from each animal in all groups. Colorimetric assays were employed to
      determine gastric tissue and erythrocyte levels of MDA and GSH, and SOD and GPX
      activities. Adrenalectomy in group II rats caused a marked decrease of SOD and
      GPX activities and MDA levels, and an increase of GSH levels in gastric tissue
      and erythrocyte, when compared to sham-operated rats. However, especially
      epinephrine injection after adrenalectomy resulted in a significantly increase of
      measured antioxidant enzyme activities and GSH levels in both gastric tissue and
      erythrocyte. These results indicate that adrenalectomy appeared to alter the
      levels of antioxidants and lipid peroxidation product in gastric tissue and
      erythrocyte. Thus, the present study provides a physiological regulatory role of
      adrenal gland in the maintenance of oxidant/antioxidant balance in gastric tissue
      and erythrocyte.

PMID- 17440231
TI  - Interference by leptin with Helicobacter pylori lipopolysaccharide-induced
      cytosolic phospholipase A2 activation in gastric mucosal cells.
AB  - Activation of cytosolic phospholipase A(2) (cPLA(2)) by bacterial LPS for the
      rapid release of arachidonic acid from membrane phospholipids is considered a key
      step in the generation of platelet-activating factor (PAF), recognized as the
      most proximal mediator of inflammatory events triggered by bacterial infection.
      In this study, we report on the role of leptin in modulation of the detrimental
      consequences of H. pylori LPS-induced cPLA(2) activation that result in the
      disturbances in gastric mucin synthesis. Employing gastric mucosal cells labeled
      with [(3)H] arachidonic acid, we show that H. pylori LPS-induced cPLA(2)
      activation, associated with up-regulation in apoptosis and PAF generation, and
      the impairment in gastric mucin synthesis, was subject to a dose-dependent
      suppression by leptin, as well as the inhibition by MAFP, a specific inhibitor of
      cPLA(2). A potentiation in the countering capacity of leptin on the LPS-induced
      up-regulation in apoptosis, arachidonic acid release and PAF generation was
      attained in the presence of ERK inhibitor, PD98059, while PI3K inhibitor,
      wortmannin had no effect. On the other hand, the prevention by leptin of the LPS
      detrimental effect on mucin synthesis was subject to suppression by wortmannin,
      an inhibitor of PI3K as well as the inhibitor of ERK, PD98059. Moreover,
      potentiation in the effect of leptin on the LPS-induced decrease in mucin
      synthesis was attained with cPLA(2) inhibitor, MAFP as well as PAF receptor
      antagonist, BN52020. The results of our findings point to H. pylori LPS-induced
      ERK-dependent cPLA(2) activation as a critical factor influencing the level of
      PAF generation, and hence the extent of pathological consequences of H. pylori
      infection on the synthesis of gastric mucin. Furthermore, we show that leptin
      counters the pathological consequences of H. pylori-induced cPLA(2) activation on
      gastric mucin synthesis through the involvement in signaling events controlled by
      MAPK/ERK and PI3K pathways.

PMID- 17440232
TI  - Endotoxemia in newborn rats attenuates acute pancreatitis at adult age.
AB  - Bacterial endotoxin (lipopolysaccharide, LPS), at high concentration is
      responsible for sepsis, and neonatal mortality, however low concentration of LPS
      protected the pancreas against acute damage. The aim of this study was to
      investigate the effect of exposition of suckling rats to LPS on the course of
      acute pancreatitis at adult age. Suckling rat (30-40g) received intraperitoneal
      (i.p.) injection of saline (control) or LPS from Escherichia coli or Salmonella
      typhi (5, 10 or 15 mg/kg-day) during 5 consecutive days. Two months later these
      rats have been subjected to i.p. cearulein infusion (25 microg/kg) to produce
      caerulein-induced pancreatitis (CIP). The following parameters were tested:
      pancreatic weight and morphology, plasma amylase and lipase activities,
      interleukin 1beta (IL-1 beta), interleukin 6 (IL-6), and interleukin 10 (IL-10)
      plasma concentrations. Pancreatic concentration of superoxide dismutase (SOD) and
      lipid peroxidation products; malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE)
      have been also measured. Caerulein infusion produced CIP in all animals tested,
      that was confirmed by histological examination. In the rats, which have been
      subjected in the neonatal period of life to LPS at doses 10 or 15 mg/kg-day x 5
      days, all manifestations of CIP have been reduced. In these animals acute
      inflammatory infiltration of pancreatic tissue and pancreatic cell vacuolization
      have been significantly diminished. Also pancreatic weight, plasma lipase and
      alpha-amylase activities, as well as plasma concentrations of IL-1beta and IL-6
      have been markedly decreased, whereas plasma anti-inflammatory IL-10
      concentration was significantly increased in these animals as compared to the
      control rats, subjected in the infancy to saline injection instead of LPS.
      Caerulein-induced fall in pancreatic SOD concentration was reversed and
      accompanied by significant reduction of MDA + 4 HNE in the pancreatic tissue. The
      effects of LPS derived from E. coli or S. typhi were similar. Pretreatment of
      suckling rats with LPS at dose of 10 mg/kg-day x 5 days resulted in the most
      prominent attenuation of acute pancreatitis at adult age, whereas LPS at dose of
      5 mg/kg-day x 5 days given to the neonatal rats failed to affect significantly
      acute pancreatitis induced in these animals 2 months later. We conclude that: 1/
      Prolonged exposition of suckling rats to bacterial endotoxin attenuated acute
      pancreatitis induced in these animals at adult age. 2/ This effect could be
      related to the increased concentration of antioxidative enzyme SO in the
      pancreatic tissue and to the modulation of cytokines production in these animals.

PMID- 17440234
TI  - The effects of indomethacin on angiogenic factors mRNA expression in renal cortex
      of healthy rats.
AB  - Indomethacin is a nonsteroidal anti-inflammatory drug used frequently to control
      chronic or temporary pain. In the kidney, indomethacin decreases medullary and
      cortical perfusion, resulting in hypoxia. Kidney hypoxia has many effects,
      including changes in gene expression, and is a strong stimulus for angiogenesis.
      Other angiogenic factors include vascular endothelial growth factor (VEGF), basic
      fibroblast growth factor (FGF-2), transforming growth factor beta 1 (TGFbeta1),
      and platelet-derived growth factor (PDGF). Our goal was to examine the influence
      of indomethacin on mRNA expression of these factors and their selected receptors
      in the renal cortex of healthy rats. Groups of 8 healthy, male, six-week-old
      Wistar rats received either indomethacin (5 mg/kg/day) or placebo orally for
      three months. RNA from renal cortex biopsies was analyzed by real-time polymerase
      chain reaction to quantify the mRNA levels of each cytokine. We observed
      significantly higher mRNA levels for VEGF (1.73-fold), FGF-2 (5.6-fold) and
      TGFbeta receptor III (2.93-fold), PDGF receptor alpha (2.93-fold) and receptor
      beta (2.91-fold) in rats receiving indomethacin compared to rats given placebo (p
      < 0.05). Amounts of mRNA for TGFbeta1, PDGF, FGF receptors 1 and 2 and TGFbeta
      receptor I did not differ between analysed groups. Our data indicates that
      indomethacin may regulate the expression of potent angiogenic factors VEGF and
      FGF-2.

PMID- 17440233
TI  - Renal tissue NO and intrarenal haemodynamics during experimental variations of NO
      content in anaesthetised rats.
AB  - Direct renal nitric oxide (NO) measurements were infrequent and no simultaneous
      measurements of renal cortical and medullary NO and local perfusion. Large
      surface NO electrodes were placed in renal cortex and medulla of anaesthetised
      rats; simultaneously, renal blood flow (RBF, index of cortical perfusion) and
      medullary laser-Doppler flux (MBF) were determined. NO synthase inhibitors:
      nonselective (L-NAME) or selective for neuronal NOS (nNOS) (S-methyl
      thiocitrulline, SMTC), and NO donor (SNAP), were used to manipulate tissue NO.
      Baseline tissue NO was significantly higher in medulla (703+/-49 NM) than in
      cortex (231+/-17 nM). Minimal cortical and medullary NO current measured after
      maximal L-NAME dose (2.4 mg kg(-1) i.v.) was taken as tissue NO zero kevel. This
      dose decreased RBF and MBF significantly (-43%). SMTC, 1.2 mg kg(-1) h(-1) i.v.,
      significantly decreased tissue NO by 105+/-32 nM in cortex and 546+/-64 nM in
      medulla, RBF and MBF decreased 30% and 20%, respectively. Renal artery infusion
      of SNAP, 0.24 mg kg(-1) min(-1) significantly increased tissue NO by 139+/-18 nM
      in cortex and 948+/-110 nM in medulla. Since inhibition of nNOS decreased
      medullary NO by 80% and MBF by 20% only, this isoform has probably minor role in
      the maintenance of medullary perfusion.

PMID- 17440236
TI  - A software tool for modification of human voxel models used for application in
      radiation protection.
AB  - This note describes a new software tool called 'VolumeChange' that was developed
      to modify the masses and location of organs of virtual human voxel models. A
      voxel model is a three-dimensional representation of the human body in the form
      of an array of identification numbers that are arranged in slices, rows and
      columns. Each entry in this array represents a voxel; organs are represented by
      those voxels having the same identification number. With this tool, two human
      voxel models were adjusted to fit the reference organ masses of a male and a
      female adult, as defined by the International Commission on Radiological
      Protection (ICRP). The alteration of an already existing voxel model is a
      complicated process, leading to many problems that have to be solved. To solve
      those intricacies in an easy way, a new software tool was developed and is
      presented here. If the organs are modified, no bit of tissue, i.e. voxel, may
      vanish nor should an extra one appear. That means that organs cannot be modified
      without considering the neighbouring tissue. Thus, the principle of organ
      modification is based on the reassignment of voxels from one organ/tissue to
      another; actually deleting and adding voxels is only possible at the external
      surface, i.e. skin. In the software tool described here, the modifications are
      done by semi-automatic routines but including human control. Because of the
      complexity of the matter, a skilled person has to validate that the applied
      changes to organs are anatomically reasonable. A graphical user interface was
      designed to fulfil the purpose of a comfortable working process, and an adequate
      graphical display of the modified voxel model was developed. Single organs, organ
      complexes and even whole limbs can be edited with respect to volume, shape and
      location.

PMID- 17440235
TI  - Effects of somatostatin-14 and the receptor-specific somatostatin analogs on
      chromogranin A and alpha-subunit (alpha-SU) release from "clinically
      nonfunctioning" pituitary adenoma cells incubated in vitro.
AB  - The aim of the study was to examine the effect of somatostatin (SST) and its
      analogs on the release of chromogranin A (CgA) and alpha-subunit (alpha-SU) from
      clinically non-functioning pituitary adenomas incubated in vitro. Seven pituitary
      macroadenomas surgically removed were investigated. All of the tumors were
      diagnosed before surgery as non-functioning, but they expressed either
      gonadotropins or their subunits as detected by immunohistochemistry. Two tumors
      additionally expressed prolactin and growth hormone. All adenomas also expressed
      chromogranin A (CgA) and at least 3 of 5 subtypes of somatostatin receptors. The
      cells isolated from the examined tumors were exposed in vitro to either native
      SST-14 or the following receptor-specific SST analogs: BIM-23926 (agonist of sst1
      receptor), BIM-23120 (agonist of sst2 receptor), BIM-23206 (agonist of sst5
      receptor) and BIM23A387 (somatostatin/dopamine chimera). The concentration of CgA
      was measured by means of ELISA method and of alpha-SU was measured by an
      immunoradiometric method. It was found that the exposure on SST-14 resulted in
      the decrease of CgA and alpha-SU release from tumor cells in majority of samples,
      and the effect on CgA was positively correlated with the expression of sst3 and
      also with the sst2A/sst2B expressions ratio. The inhibitory effect of SST-14 on
      CgA and alpha-SU seems also to correlate negatively with the expression of sst2B.
      CgA inhibition also correlates positively with sst5 expression. Among the other
      compounds studied, only the sst2 agonist decreased the release in all the
      investigated samples. The remaining substances (agonists of sst1 and sst5 and
      SST/DA chimera) produced the divergent changes (increased or decreased release,
      depending on the sample). The data suggest that the inhibition of CgA (and
      possibly of alpha-SU) release by SST is mediated via subtypes sst2A, sst3 and
      sst5, whereas sst2B subtype may induce the opposite effect.

PMID- 17440237
TI  - Some specific features of ionization chamber calibrations in linac x-ray beams at
      the LNE-LNHB.
AB  - The purpose of this note is to give some details about the modus operandi
      employed today to calibrate ionization chambers in radiotherapy linac photon
      beams at the Laboratoire National Henri Becquerel (LNE-LNHB). Some specific
      features are described: first the equipment (including the external monitoring
      ionization chambers), second the calculations of the profile or radial non
      uniformity correction factors (up to 0.5% effect for commonly used ionization
      chambers) and finally the calculations to get the calibration coefficients for
      customer beam qualities.

PMID- 17440238
TI  - Electric fields induced in the human body by time-varying magnetic field
      gradients in MRI: numerical calculations and correlation analysis.
AB  - The spatial distributions of the electric fields induced in the human body by
      switched magnetic field gradients in MRI have been calculated numerically using
      the commercial software package, MAFIA, and the three-dimensional, HUGO body
      model that comprises 31 different tissue types. The variation of |J|, |E| and |B|
      resulting from exposure of the body model to magnetic fields generated by typical
      whole-body x-, y- and z-gradient coils has been analysed for three different body
      positions (head-, heart- and hips-centred). The magnetic field varied at 1 kHz,
      so as to produce a rate of change of gradient of 100 T m(-1) s(-1) at the centre
      of each coil. A highly heterogeneous pattern of induced electric field and
      current density was found to result from the smoothly varying magnetic field in
      all cases, with the largest induced electric fields resulting from application of
      the y-gradient, in agreement with previous studies. By applying simple
      statistical analysis to electromagnetic quantities within axial planes of the
      body model, it is shown that the induced electric field is strongly correlated to
      the local value of resistivity, and the induced current density exhibits even
      stronger correlation with the local conductivity. The local values of the
      switched magnetic field are however shown to bear little relation to the local
      values of the induced electric field or current density.

PMID- 17440239
TI  - A delivery transfer function (DTF) analysis for helical tomotherapy.
AB  - The previous theoretical work of a delivery transfer function (DTF) in
      radiotherapy is expanded to include the unique intensity modulation method of
      helical tomotherapy. In addition to the collimation of each beamlet, and the
      Gaussian scatter convolution spreading of the dose that other radiotherapy units
      have, helical tomotherapy uses 51 small arcs of varying lengths to adjust the
      intensity. The blurring from these arcs is not taken into account during
      treatment planning. A theoretical DTF is constructed, and a calculation is
      performed which includes this unique source motion in relation to the other DTF
      components. Various typical delivery parameters are used to generate resolution
      maps for a constant intensity projection. Near the isocenter, the transverse (to
      a given beam direction) blurring is small but at larger radii (>6 cm), the source
      blurring dominates over leaf size. For most clinical situations, this inherent
      source motion blurring is expected to be negligible.

PMID- 17440240
TI  - Measuring optical temperature coefficients of Intralipid.
AB  - The temperature sensitivities of absorption and reduced scattering coefficients
      in the range 700-1000 nm are determined for the liquid phantom Intralipid using
      spatially resolved continuous wave measurements. The measurements were conducted
      on a 10 L heated volume of 1% Intralipid subjected to a 40-30 degrees C cooling
      regime. The temperature sensitivities of the absorbance coefficients are similar
      to that expected for pure water. However, the reduced scattering coefficients are
      more sensitive than can be explained by temperature related density changes, and
      show an unexpected relationship with wavelength. We have also found that
      temperature perturbations provide a useful means to evaluate instrument model
      performance.

PMID- 17440241
TI  - Discrete vessel heat transfer in perfused tissue--model comparison.
AB  - The aim of this paper is to compare two methods of calculating heat transfer in
      perfused biological tissue using a discrete vessel description. The methods
      differ in two important aspects: the representation of the vascular system and
      the algorithm for calculating the heat flux between tissue and blood vessels. The
      first method was developed at the University of Utrecht between 1994 and 1998 and
      has been used in several clinical applications. The second method has been
      proposed by the first author. The methods are briefly described, their
      assumptions and limitations are discussed. Finally, the test simulation is
      introduced and the results produced by both methods are compared. The test
      indicates that the simpler, and less computationally intensive method proposed by
      the present author for calculating 2D problems containing countercurrent blood
      vessel systems can reproduce quite well some features of the solution obtained by
      the more complex 3D method. The observed discrepancies could be explained on
      physical grounds.

PMID- 17440242
TI  - Bayesian estimation of pharmacokinetic parameters for DCE-MRI with a robust
      treatment of enhancement onset time.
AB  - When applying pharmacokinetic (PK) models to dynamic contrast enhanced MRI (DCE
      MRI) data it is important to appropriately deal with the enhancement onset time,
      because errors in the onset time will affect the PK parameter estimates. This
      paper presents a Bayesian approach to the estimation of the PK parameters k(ep)
      and K(trans) that robustly treats the onset time. This approach involves the
      computation of an analytically intractable integral, so two approximate methods
      are developed. The first uses adaptive numerical quadrature, which produces
      results accurate to a given tolerance, and the other a simple approximation with
      a summation. These approaches are compared with each other, and with the standard
      least-squares (LS) approach. The results of a Monte Carlo experiment show that
      the LS approach produces biased estimates when k(ep) is large and K(trans) is
      small, whereas both the Bayesian methods are unbiased. The two Bayesian methods
      produce very similar estimates, but the simple summation method requires less
      than half the computation time of either the LS, or the quadrature approximation.
      The standard deviation of the LS estimates is shown to be larger than either of
      the Bayesian estimates, while uncertainty estimates based around a Hessian
      approximation are shown to be too small for all three methods. A more detailed
      method of assessing the uncertainty of the Bayesian approach is described, and
      the results show that this is a more accurate description of the estimation
      uncertainty.

PMID- 17440243
TI  - Small angle scatter imaging from wide beam diffraction patterns.
AB  - In this paper we report on the extension of the technique of mapping small angle
      x-ray scatter (SAXS) across a soft material specimen several millimetres square.
      In the conventional SAXS mapping technique a pencil beam of x-rays is raster
      scanned over the specimen with the scatter pattern recorded from each point in
      the raster. In our technique a wide, parallel beam is used, speeding up the data
      collection time considerably. An image processing algorithm is used to separate
      the scatter pattern features from individual points along the line of the beam.
      To test the efficacy of the technique a phantom was constructed using gelatin and
      rat tail tendon collagen. Collagen fibres in the phantom were arranged in
      quarters horizontally, diagonally and vertically leaving one quarter with just
      gelatin. The phantom was used to collect both raster scanned sets of SAXS
      patterns spaced at 0.25 mm horizontally and vertically and also a wide beam data
      set. The width of the beam in this case was approximately 7 mm. Using the third
      order diffraction of rat tail tendon intensity data were gathered from each SAXS
      pattern and used to construct a map. Data from the raster scan image and that
      from the wide beam are compared. Finally using a phantom made from dehydrated rat
      tail tendon and paraffin wax a tomographic slice constructed using data from SAXS
      patterns is shown.

PMID- 17440244
TI  - Viscoelasticity imaging using ultrasound: parameters and error analysis.
AB  - Techniques are being developed to image viscoelastic features of soft tissues
      from time-varying strain. A compress-hold-release stress stimulus commonly used
      in creep-recovery measurements is applied to samples to form images of elastic
      strain and strain retardance times. While the intended application is diagnostic
      breast imaging, results in gelatin hydrogels are presented to demonstrate the
      techniques. The spatiotemporal behaviour of gelatin is described by linear
      viscoelastic theory formulated for polymeric solids. Measured creep responses of
      polymers are frequently modelled as sums of exponentials whose time constants
      describe the delay or retardation of the full strain response. We found the
      spectrum of retardation times tau to be continuous and bimodal, where the
      amplitude at each tau represents the relative number of molecular bonds with a
      given strength and conformation. Such spectra indicate that the molecular weight
      of the polymer fibres between bonding points is large. Imaging parameters are
      found by summarizing these complex spectral distributions at each location in the
      medium with a second-order Voigt rheological model. This simplification reduces
      the dimensionality of the data for selecting imaging parameters while preserving
      essential information on how the creeping deformation describes fluid flow and
      collagen matrix restructuring in the medium. The focus of this paper is on
      imaging parameter estimation from ultrasonic echo data, and how jitter from hand
      held force applicators used for clinical applications propagate through the
      imaging chain to generate image noise.

PMID- 17440245
TI  - Robust intravascular optical coherence elastography by line correlations.
AB  - We present a new method for intravascular optical coherence elastography, which
      is robust against motion artefacts. It employs the correlation between adjacent
      lines, instead of subsequent frames. Pressure to deform the tissue is applied
      synchronously with the line scan rate of the optical coherence tomography (OCT)
      instrument. The viability of the method is demonstrated with a simulation study.
      We find that the root mean square (rms) error of the displacement estimate is
      0.55 microm, and the rms error of the strain is 0.6%. It is shown that high
      strain spots in the vessel wall, such as observed at the sites of vulnerable
      atherosclerotic lesions, can be detected with the technique.

PMID- 17440246
TI  - Improvement of field matching in segmented-field electron conformal therapy using
      a variable-SCD applicator.
AB  - The purpose of the present study is to demonstrate that the use of an electron
      applicator with energy-dependent source-to-collimator distances (SCDs) will
      significantly improve the dose homogeneity for abutted electron fields in
      segmented-field electron conformal therapy (ECT). Multiple Coulomb scattering
      theory was used to calculate and study the P(80-20) penumbra width of off-axis
      dose profiles as a function of air gap and depth. Collimating insert locations
      with air gaps (collimator-to-isocenter distance) of 5.0, 7.5, 11.5, 17.5 and 19.5
      cm were selected to provide equal P(80-20) at a depth of 1.5 cm in water for
      energies of 6, 9, 12, 16 and 20 MeV, respectively, for a Varian 2100EX radiation
      therapy accelerator. A 15 x 15 cm(2) applicator was modified accordingly, and
      collimating inserts used in the variable-SCD applicator for segmented-field ECT
      were constructed with diverging edges using a computer-controlled hot-wire
      cutter, which resulted in 0.27 mm accuracy in the abutted edges. The resulting
      electron beams were commissioned for the pencil-beam algorithm (PBA) on the
      Pinnacle(3) treatment planning system. Four hypothetical planning target volumes
      (PTVs) and one patient were planned for segmented-field ECT using the new
      variable-SCD applicator, and the resulting dose distributions were compared with
      those calculated for the identical plans using the conventional 95 cm SCD
      applicator. Also, a method for quality assurance of segmented-field ECT dose
      plans using the variable-SCD applicator was evaluated by irradiating a
      polystyrene phantom using the treatment plans for the hypothetical PTVs.
      Treatment plans for all four of the hypothetical PTVs using the variable-SCD
      applicator showed significantly improved dose homogeneity in the abutment regions
      of the segmented-field ECT plans. This resulted in the dose spread (maximum dose
      minimum dose), sigma, and D(90-10) in the PTV being reduced by an average of 32%,
      29% and 32%, respectively. Reductions were most significant for abutted fields of
      nonadjacent energies. Planning segmented-field ECT using the variable-SCD
      applicator for a patient with recurrent squamous cell carcinoma of the left ear
      showed the dose spread, sigma, and D(90-10) of the dose distribution in the PTV
      being reduced by an average of 38%, 22% and 22%, respectively. The measured and
      calculated dose in a polystyrene phantom resulting from the variable-SCD,
      segmented-field ECT plans for the hypothetical PTVs showed good agreement;
      however, isolated differences between dose calculation and measurement indicated
      the need for a more accurate dose algorithm than the PBA for segmented-field ECT.
      These results confirmed our hypothesis that using the variable-SCD applicator for
      segmented-field ECT results in the PTV dose distribution becoming more homogenous
      and being within the range of 85-105% of the 'given dose'. Clinical
      implementation of this method requires variable-SCD applicators, and the design
      used in the present work should be acceptable, as should our methods for
      construction of the inserts. Dose verification measurements in a polystyrene
      phantom and the recommended improvements in dose calculation should be
      appropriate for quality assurance of segmented-field ECT.

PMID- 17440247
TI  - Calculation of the positron distribution from 15O nuclei formed in nuclear
      reactions in human tissue during proton therapy.
AB  - To measure and verify the dose distribution within a patient during proton
      therapy, indirect methods must be used. One such method is to use positron
      emission tomography (PET), which takes advantage of the nuclear reactions that
      take place between protons and nuclei in the tissue. The dominant nuclear
      reaction in human muscle tissue involves oxygen nuclei and produces radioactive
      oxygen-15. Oxygen-15 decays through positron emission, and it is these positrons
      that go on to annihilate that produce the signal used in the PET technique.
      Finding the distribution of annihilation points, however, is not analogous to
      finding the proton dose distribution. The oxygen-15 and positrons travel finite
      distances within the tissue, blurring the detected PET distribution from the
      desired proton distribution. Through Monte Carlo modelling, an analysis of the
      differences between the positron, oxygen-15 and proton distributions has been
      made. The program SRIM 2003 was used to find the correlation between the three
      distributions within simulated muscle tissue. Results show that the distal edge
      of the proton Bragg peak correlates with the detectable positron distribution,
      which is a section of the dose distribution of interest due to the steep dose
      gradient and position of adjacent critical structures.

PMID- 17440248
TI  - Measurements of wavelength shifting (WLS) fibre readout for a highly multiplexed,
      depth-encoding PET detector.
AB  - We are attempting to develop a laboratory PET scanner for mouse imaging that
      utilizes far fewer detectors and channels of electronics, thus reducing cost,
      whilst retaining state-of-the-art performance. The detectors are based on LSO
      arrays read out by wavelength shifting (WLS) fibres placed on the top and the
      bottom of the arrays. Depth of interaction information will be obtained from the
      ratio of the signals at either end of the array. For acceptable performance, it
      is critical to maximize collection of light photons from the ends of the fibres
      and to minimize the optical crosstalk between adjacent fibres. Factors which can
      affect the light collection and crosstalk were studied, including coupling
      materials between fibres and crystals, reflectors wrapped around the fibre sides
      and ends, fibre size and shape, and number of layers of fibre cladding.
      Properties of WLS fibres such as the transmission attenuation and transverse
      absorption were also studied. The light yield from 2 x 2 x 10 mm(3) LSO crystals
      collected from the end of a 2 x 2 x 30 mm(3) WLS fibre was up to 24% (typical
      values 16-20%) of that obtained by direct coupling of the LSO crystal. This light
      collection efficiency appears to be sufficient for decoding interaction position
      in these detectors.

PMID- 17440249
TI  - Quantification of beta+ activity generated by hard photons by means of PET.
AB  - Positron emission tomography (PET) as a method for quality assurance in
      radiotherapy is well investigated in the case of therapy with carbon ion beams
      and successfully applied at the Heavy Ion Medical Accelerator at Chiba (HIMAC),
      Japan, and the Gesellschaft fur Schwerionenforschung (GSI), Germany. By measuring
      the beta(+) activity distribution during the irradiation (in-beam PET), valuable
      information on the precision of the dose deposition can be obtained. To extend
      this efficient technique to other radiation treatment modalities may be
      worthwhile. For example, since positron emitters are generated by high-energy
      photons with energies above 20 MeV due to (gamma, n) reactions (predominantly
      (11)C and (15)O in tissue), in-beam PET seems to be feasible for radiation
      therapy with high-energy photons as also shown in Geant4 simulations.
      Quantitative results on the activation of tissue-equivalent materials at hard
      photon beams were obtained by performing off-beam PET experiments. Homogeneous
      PMMA phantoms as well as inhomogeneous phantoms were irradiated with high-energy
      bremsstrahlung. After the irradiation the distributions of the generated positron
      emitters in the phantoms were measured using a conventional PET scanner.
      Furthermore, the depth-dose distributions were determined by means of optically
      stimulated luminescence detectors. In the experiments an activity per dose
      comparable to that produced in a typical patient irradiation with carbon ions
      could be achieved for 34 MV bremsstrahlung. In addition, a high contrast in the
      PET images for materials with different density and stoichiometry could be
      detected. Thus, further research concerning the development of in-beam PET seems
      to be worthwhile.

PMID- 17440250
TI  - The relative effects of arterial curvature and lumen diameter on wall shear
      stress distributions in human right coronary arteries.
AB  - This study looks at blood flow in four different human right coronary arteries
      (RCAs), which have been reconstructed from bi-plane angiograms. A generalized
      power-law model of blood viscosity is used to study the blood flow at a
      particular point in the cardiac cycle. Large differences are found in the wall
      shear stress magnitude (WSS) distributions in the four arteries, leading to the
      conclusion that it is not possible to make generalizations based on the study of
      a single artery. The pattern of WSS is found to be related to the geometry of a
      particular artery, that is, lumen diameter and arterial curvature as well as a
      combination of these two factors. There is a strong correlation between WSS and
      reciprocal radius and a weaker correlation between high curvature and extremes of
      WSS, with high WSS on the 'inside' of a bend and low WSS on the 'outside' of a
      bend. This is in contrast to the situation for a simple curved tube with constant
      radius where the inverse is observed. For each artery, a region proximal to the
      acute margin is identified where low WSS is found and where WSS is lower on the
      'inner' wall of the RCA than on the 'outer' wall. This region is one where
      several studies have found that the human RCA preferentially exhibits
      atherogenesis.

PMID- 17440251
TI  - X-ray phase imaging of biological soft tissue using a direct-sensing x-ray HARP
      tube camera.
AB  - A HDTV camera having a direct-sensing x-ray high-gain avalanche rushing amorphous
      photoconductor (HARP) tube was used, for the first time, to acquire x-ray phase
      maps. The tube can achieve a high sensitivity as a result of the avalanche
      multiplication process in the HARP target. A beryllium plate, rather than a glass
      plate, was used as the face plate of the tube to minimize the loss of x-rays due
      to absorption, and a 15 microm thick HARP target was directly formed on it. In
      the experiment, the x-ray phase shifts produced by a rat liver were measured
      using synchrotron x-rays (lambda = 0.0766 nm) and a triple Laue-case (LLL) x-ray
      interferometer. Interference patterns produced by the sample were observed with
      the direct-sensing x-ray HARP tube camera. A voltage of 1300 V was applied to the
      HARP target to give an output signal gain of two. The camera was operated in 1125
      scanning-line mode, and real-time images were stored on a workstation at a rate
      of 30 images/s with an image format of 960 (H) x 1100 (V) pixels. A phase-map
      image of the sample was successfully obtained using the fringe scanning method
      and phase unwrapping. The observed phase shifts ranged from 50 degrees to 200
      degrees . Trees of blood vessels in the rat liver were clearly depicted without
      using a contrast agent. The spatial resolution of the x-ray camera was estimated
      to be better than 35 microm in the vertical direction and 100 microm in the
      horizontal direction.

PMID- 17440252
TI  - Development and characteristics of the HANARO neutron irradiation facility for
      applications in the boron neutron capture therapy field.
AB  - The HANARO neutron irradiation facility for various applications in the boron
      neutron capture therapy (BNCT) field was developed, and its characteristics were
      investigated. In order to obtain the sufficient thermal neutron flux with a low
      level of contamination by fast neutrons and gamma rays, a radiation filtering
      method was adopted. The radiation filter was designed by using a silicon single
      crystal, cooled by liquid nitrogen, and a bismuth crystal. The installation of
      the main components of the irradiation facility and the irradiation room was
      finished. Neutron beam characteristics were measured by using bare and cadmium
      covered gold foils and wires. The in-phantom neutron flux distribution was
      measured for flux mapping inside the phantom. The gamma-ray dose was determined
      by using TLD-700 thermoluminescence dosimeters. The thermal and fast neutron
      fluxes and the gamma-ray dose were calculated by using the MCNP code, and they
      were compared with experimental data. The thermal neutron flux and Cd ratio
      available at this facility were confirmed to be 1.49 x 10(9) n cm(-2) s(-1) and
      152, respectively. The maximum neutron flux inside the phantom was measured to be
      2.79 x 10(9) n cm(-2) s(-1) at a depth of 3 mm in the phantom. The two
      dimensional in-phantom neutron flux distribution was determined, and significant
      neutron irradiation was observed within 20 mm from the phantom surface. The gamma
      ray dose rate for the free beam condition was expected to be about 80 cGy h(-1).
      These experimental results were reasonably well supported by calculation using
      the facility design code. This HANARO thermal neutron facility can be used not
      only for clinical trials, but also for various pre-clinical studies in the BNCT
      field.

PMID- 17440253
TI  - Optimizing multi-pinhole SPECT geometries using an analytical model.
AB  - State-of-the-art multi-pinhole SPECT devices allow for sub-mm resolution imaging
      of radio-molecule distributions in small laboratory animals. The optimization of
      multi-pinhole and detector geometries using simulations based on ray-tracing or
      Monte Carlo algorithms is time-consuming, particularly because many system
      parameters need to be varied. As an efficient alternative we develop a continuous
      analytical model of a pinhole SPECT system with a stationary detector set-up,
      which we apply to focused imaging of a mouse. The model assumes that the multi
      pinhole collimator and the detector both have the shape of a spherical layer, and
      uses analytical expressions for effective pinhole diameters, sensitivity and
      spatial resolution. For fixed fields-of-view, a pinhole-diameter adapting
      feedback loop allows for the comparison of the system resolution of different
      systems at equal system sensitivity, and vice versa. The model predicts that (i)
      for optimal resolution or sensitivity the collimator layer with pinholes should
      be placed as closely as possible around the animal given a fixed detector layer,
      (ii) with high-resolution detectors a resolution improvement up to 31% can be
      achieved compared to optimized systems, (iii) high-resolution detectors can be
      placed close to the collimator without significant resolution losses, (iv)
      interestingly, systems with a physical pinhole diameter of 0 mm can have an
      excellent resolution when high-resolution detectors are used.

PMID- 17440254
TI  - Estimating radiation doses from multidetector CT using Monte Carlo simulations:
      effects of different size voxelized patient models on magnitudes of organ and
      effective dose.
AB  - The purpose of this work is to examine the effects of patient size on radiation
      dose from CT scans. To perform these investigations, we used Monte Carlo
      simulation methods with detailed models of both patients and multidetector
      computed tomography (MDCT) scanners. A family of three-dimensional, voxelized
      patient models previously developed and validated by the GSF was implemented as
      input files using the Monte Carlo code MCNPX. These patient models represent a
      range of patient sizes and ages (8 weeks to 48 years) and have all radiosensitive
      organs previously identified and segmented, allowing the estimation of dose to
      any individual organ and calculation of patient effective dose. To estimate
      radiation dose, every voxel in each patient model was assigned both a specific
      organ index number and an elemental composition and mass density. Simulated CT
      scans of each voxelized patient model were performed using a previously developed
      MDCT source model that includes scanner specific spectra, including bowtie
      filter, scanner geometry and helical source path. The scan simulations in this
      work include a whole-body scan protocol and a thoracic CT scan protocol, each
      performed with fixed tube current. The whole-body scan simulation yielded a
      predictable decrease in effective dose as a function of increasing patient
      weight. Results from analysis of individual organs demonstrated similar trends,
      but with some individual variations. A comparison with a conventional dose
      estimation method using the ImPACT spreadsheet yielded an effective dose of 0.14
      mSv mAs(-1) for the whole-body scan. This result is lower than the simulations on
      the voxelized model designated 'Irene' (0.15 mSv mAs(-1)) and higher than the
      models 'Donna' and 'Golem' (0.12 mSv mAs(-1)). For the thoracic scan protocol,
      the ImPACT spreadsheet estimates an effective dose of 0.037 mSv mAs(-1), which
      falls between the calculated values for Irene (0.042 mSv mAs(-1)) and Donna
      (0.031 mSv mAs(-1)) and is higher relative to Golem (0.025 mSv mAs(-1)). This
      work demonstrates the ability to estimate both individual organ and effective
      doses from any arbitrary CT scan protocol on individual patient-based models and
      to provide estimates of the effect of patient size on these dose metrics.

PMID- 17440255
TI  - Multispectral imaging and artificial neural network: mimicking the management
      decision of the clinician facing pigmented skin lesions.
AB  - Various instruments based on acquisition and elaboration of images of pigmented
      skin lesions have been developed in an attempt to in vivo establish whether a
      lesion is a melanoma or not. Although encouraging, the response of these
      instruments, e.g. epiluminescence microscopy, reflectance spectrophotometry and
      fluorescence imaging, cannot currently replace the well-established diagnostic
      procedures. However, in place of the approach to instrumentally assess the
      diagnosis of the lesion, recent studies suggest that instruments should rather
      reproduce the assessment by an expert clinician of whether a lesion has to be
      excised or not. The aim of this study was to evaluate the performance of a
      spectrophotometric system to mimic such a decision. The study involved 1794
      consecutively recruited patients with 1966 doubtful cutaneous pigmented lesions
      excised for histopathological diagnosis and 348 patients with 1940 non-excised
      lesions because clinically reassuring. Images of all these lesions were acquired
      in vivo with a multispectral imaging system. The data set was randomly divided
      into a train (802 reassuring and 1003 excision-needing lesions, including 139
      melanomas), a verify (464 reassuring and 439 excision-needing lesions, including
      72 melanomas) and a test set (674 reassuring and 524 excision-needing lesions,
      including 76 melanomas). An artificial neural network (ANN(1)) was set up to
      perform the classification of the lesions as excision-needing or reassuring,
      according to the expert clinicians' decision on how to manage each examined
      lesion. In the independent test set, the system was able to emulate the
      clinicians with a sensitivity of 88% and a specificity of 80%. Of the 462
      correctly classified as excision-needing lesions, 72 (95%) were melanomas. No
      major variations in receiver operating characteristic curves were found between
      the test and the train/verify sets. On the same data set, a further artificial
      neural network (ANN(2)) was then architected to perform classification of the
      lesions as melanoma or non-melanoma, according to the histological diagnosis.
      Having set the sensitivity in recognizing melanoma to 95%, ANN(1) resulted to be
      significantly better in the classification of reassuring lesions than ANN(2).
      This study suggests that multispectral image analysis and artificial neural
      networks could be used to support primary care physicians or general
      practitioners in identifying pigmented skin lesions that require further
      investigations.

PMID- 17440256
TI  - Visualization of bonding at an inclusion boundary using axial-shear strain
      elastography: a feasibility study.
AB  - Ultrasound elastography produces strain images of compliant tissues under quasi
      static compression. In axial-shear strain elastography, the local axial-shear
      strain resulting from application of quasi-static axial compression to an
      inhomogeneous material is imaged. The overall hypothesis of this work is that the
      pattern of axial-shear strain distribution around the inclusion/background
      interface is completely determined by the bonding at the interface after
      normalization for inclusion size and applied strain levels, and that it is
      feasible to extract certain features from the axial-shear strain elastograms to
      quantify this pattern. The mechanical model used in this study consisted of a
      single stiff circular inclusion embedded in a homogeneous softer background.
      First, we performed a parametric study using finite-element analysis (FEA) (no
      ultrasound involved) to identify possible features that quantify the pattern of
      axial-shear strain distribution around an inclusion/background interface. Next,
      the ability to extract these features from axial-shear strain elastograms,
      estimated from simulated pre- and post-compression noisy RF data, was
      investigated. Further, the feasibility of extracting these features from in vivo
      breast data of benign and malignant tumors was also investigated. It is shown
      using the FEA study that the pattern of axial-shear strain distribution is
      determined by the degree of bonding at the inclusion/background interface. The
      results suggest the feasibility of using normalized features that capture the
      region of positive and negative axial-shear strain area to quantify the pattern
      of the axial-shear strain distribution. The simulation results showed that it was
      feasible to extract the features, as identified in the FEA study, from axial
      shear strain elastograms. However, an effort must be made to obtain axial-shear
      strain elastograms with the highest signal-to-noise ratio (SNR(asse)) possible,
      without compromising the resolution. The in vivo results demonstrated the
      feasibility of producing and extracting features from the axial-shear strain
      elastograms from breast data. Furthermore, the in vivo axial-shear strain
      elastograms suggest an additional feature not identified in the simulations that
      may potentially be used for distinguishing benign from malignant tumors-the
      proximity of the axial-shear strain regions to the inclusion/background interface
      identified in the sonogram.

PMID- 17440257
TI  - Mental self-government: development of the additional democratic learning style
      scale using Rasch measurement models.
AB  - This paper describes the development and validation of a democratic learning
      style scale intended to fill a gap in Sternberg's theory of mental self
      government and the associated learning style inventory (Sternberg, 1988, 1997).
      The scale was constructed as an 8-item scale with a 7-category response scale.
      The scale was developed following an adapted version of DeVellis' (2003)
      guidelines for scale development. The validity of the Democratic Learning Style
      Scale was assessed by items analysis using graphical loglinear Rasch models
      (Kreiner and Christensen, 2002, 2004, 2006) The item analysis confirmed that the
      full 8-item revised Democratic Learning Style Scale fitted a graphical loglinear
      Rasch model with no differential item functioning but weak to moderate uniform
      local dependence between two items. In addition, a reduced 6-item version of the
      scale fitted the pure Rasch model with a rating scale parameterization. The
      revised Democratic Learning Style Scale can therefore be regarded as a sound
      measurement scale meeting requirements of both construct validity and
      objectivity.

PMID- 17440258
TI  - Measuring Math Anxiety (in Spanish) with the Rasch Rating Scale Model.
AB  - Two successive studies probed the psychometric properties of a Math Anxiety
      questionnaire (in Spanish) by means of the Rasch Rating Scale Model. Participants
      were 411 and 216 Spanish adolescents. Convergent validity was examined by
      correlating the scale with both the Fennema and Sherman Attitude Scale and a math
      achievement test. The results show that the scores are psychometrically
      appropriate, and replicate those reported in meta-analyses: medium-sized negative
      correlations with achievement and with attitudes toward mathematics, as well as
      moderate sex-related differences (with girls presenting higher anxiety levels
      than boys).

PMID- 17440259
TI  - Using Rasch analysis to construct a Clinical Problem-Solving Inventory in the
      dental clinic: a case study.
AB  - A 28-item inventory was developed to measure the clinical problem-solving
      abilities of 3rd and 4th year dental students. The judgments of 57 expert raters
      (dental-school faculty) from four dental schools used the inventory to evaluate
      183 dental students on a 5-point rating scale. The Rasch measurement model was
      employed to examine the psychometric properties and construct validity of this
      inventory. In this study, fit statistics identified the "noise" in the data and
      residual analysis assisted in extracting a meaningful structure. The study
      results indicate that the Rasch measurement model appeared to be a useful method
      for use in producing a unidimensional instrument. All five rating categories were
      used in a coherent manner, and four discernable levels of clinical problem
      solving ability were identified. After removal of four repetitious items, a
      version of the Clinical Problem-Solving Inventory was finalized that could serve
      as a criterion measure for validating the use of a critical thinking test on the
      Dental Admission Test.

PMID- 17440260
TI  - Evidence-based practice for equating health status items: sample size and IRT
      model.
AB  - BACKGROUND: In the development of health outcome measures, the pool of candidate
      items may be divided into multiple forms, thus "spreading" response burden over
      two or more study samples. Item responses collected using this approach result in
      two or more forms whose scores are not equivalent. Therefore, the item responses
      must be equated (adjusted) to a common mathematical metric. OBJECTIVES: The
      purpose of this study was to examine the effect of sample size, test size, and
      selection of item response theory model in equating three forms of a health
      status measure. Each of the forms was comprised of a set of items unique to it
      and a set of anchor items common across forms. RESEARCH DESIGN: The study was a
      secondary data analysis of patients' responses to the developmental item pool for
      the Health of Seniors Survey. A completely crossed design was used with 25
      replications per study cell. RESULTS: We found that the quality of equatings was
      affected greatly by sample size. Its effect was far more substantial than choice
      of IRT model. Little or no advantage was observed for equatings based on 60 or 72
      items versus those based on 48 items. CONCLUSIONS: We concluded that samples of
      less than 300 are clearly unacceptable for equating multiple forms. Additional
      sample size guidelines are offered based on our results.

PMID- 17440261
TI  - Computing confidence intervals of item fit statistics in the family of Rasch
      models using the bootstrap method.
AB  - The item infit and outfit mean square errors (MSE) and their t-transformed
      statistics are widely used to screen poorly fitting items. The t-transformed
      statistics, however, do not follow the standard normal distribution so that
      hypothesis testing of item fit based on the conventional critical values is
      likely to be inaccurate (Wang and Chen, 2005). The MSE statistics are effect-size
      measures of misfit and have an expected value of unity when the data fit the
      model's expectation. Unfortunately, most computer programs for item response
      analysis do not report confidence intervals of the item infit and outfit MSE,
      mainly because their sampling distributions are analytically intractable. Hence,
      the user is left without interval estimates of the magnitudes of misfit. In this
      study, we developed a FORTRAN 90 computer program in conjunction with the
      commercial program WINSTEPS (Linacre, 2001) that yields confidence intervals of
      the item infit and outfit MSE using the bootstrap method. The utility of the
      program is demonstrated through three illustrations of simulated data sets.

PMID- 17440262
TI  - Instrument development tools and activities for measure validation using Rasch
      models: part II--validation activities.
AB  - Accumulation of validity evidence is an important part of the instrument
      development process. In Part I of a two-part series, we provided an overview of
      validity concepts and described how instrument development efforts can be
      conducted to facilitate the development of validity arguments. In this, Part II
      of the series, we identify how analyses, especially those conducted within a
      Rasch measurement framework, can be used to provide evidence to support validity
      arguments that are founded during the instrument development process.

PMID- 17440263
TI  - Kidney function and sarcopenia in the United States general population: NHANES
      III.
AB  - BACKGROUND/AIMS: It is not known whether sarcopenia is associated with levels of
      kidney function in community-dwelling adults. METHODS: Subjects were adult Third
      National Health and Nutrition Examination Survey participants in whom
      bioimpedance was performed (n = 13,770). Class I sarcopenia was defined as a
      skeletal mass index of 1-2 standard deviations below and class II sarcopenia as <
      2 standard deviations below young adult values. RESULTS: A monotonic association
      existed between increasing sarcopenia prevalence and declining glomerular
      filtration rate: > or = 90 ml/min/1.73 m2, 22.8% class I, 3.8% class II
      sarcopenia; 60-89 ml/min/1.73 m2, 33.6% class I, 5.3% class II sarcopenia, and <
      60 ml/min/1.73 m2, 50.7% class I, 9.4% class II sarcopenia (p < 0.0001). This
      association dissipated when adjustment was made for older age and more
      comorbidity. Multivariate associations (p < 0.05) of sarcopenia and chronic
      kidney disease included: older age; low income-to-poverty ratio; overweight; lack
      of exercise; low carbohydrate, fat and protein intake; hypercalcemia; low 25
      hydroxy-vitamin D3; higher diastolic blood pressure, and insulin resistance.
      CONCLUSION: Sarcopenia is common in community-dwelling adults with chronic kidney
      disease. Although causality cannot be assumed, several associations may be
      susceptible to intervention.

PMID- 17440264
TI  - [Multiple pregnancies--Part 2].
AB  - Increasing rates of multiple pregnancies with ensuing clinical problems such as
      prematurity, fetal growth disorders and specific disorders of multiple
      pregnancies are a challenge for providers of prenatal care and delivery. In
      general clinical and scientific data regarding prenatal care (e.g. use of
      tocolytics) and birth surveillance (e.g. mode of delivery) are less abundant and
      valid for multiple pregnancies than for singleton pregnancies. This is why in
      particular prematurity and supervision of birth are discussed in the following
      articles. Obviously there is need for multidisciplinary prospective multicenter
      studies on various problems of multiple pregnancies.

PMID- 17440265
TI  - [Fetal growth in multiple pregnancy].
AB  - A close surveillance of fetal growth in multiple pregnancies is mandatory for the
      prevention and/or reduction of neonatal morbidity and mortality. Multiples have
      the same genetically determined growth potential as singletons. However, this
      growth potential is restricted by the functional capacity of the placenta and
      uterus. Multiples show a specific growth pattern compared to singletons.
      Nevertheless, for clinical surveillance, the 10th percentile of singleton growth
      charts may be used, because significant differences, which may define normally
      grown multiples as small for gestational age or growth restricted, can only be
      detected at higher gestational ages, when most of the multiples may have already
      been delivered. At higher gestational ages, obstetricians should take into
      account the specific growth pattern for multiples. In multiples with growth
      discordance, it is necessary to consider or exclude the various causes, and if
      necessary the clinical follow-up has to be intensified.

PMID- 17440266
TI  - [Prematurity in multiple pregnancies].
AB  - At present, 1.5% of all pregnancies are twin pregnancies, but twin pregnancies
      account for 25% of all premature infants. The chorionicity plays an important
      role: the risk of preterm birth before 32 weeks is 5.5% in dichorial twins and
      almost double (9%) in monochorial twins. The rate of intrauterine growth
      restriction and also the perinatal mortality are twice as high in monochorial
      compared to dichorial twins. In cases of imminent preterm labour, tocolysis is
      recommended until lung maturity has been achieved. The preferred drugs, are
      oxytocin antagonists because of the increased cardiorespiratory strain in
      multiple pregnancies. Prophylactic bed rest and 'home uterine activity
      monitoring' have not been shown to improve the outcome, and a recent review
      (2005) demonstrated a twofold increase in preterm labour after cervical cerclage.
      In two large placebo-controlled studies, the rate of preterm delivery in high
      risk singleton pregnancies was significantly reduced by the regular application
      of progesterone. A potential effect on multiple pregnancies is yet to be shown.

PMID- 17440267
TI  - [Delivery of multiples, particularly of twins].
AB  - Multiples run various risks. While for triplets and higher-grade multiples
      caesarean section is the first-line mode of delivery, the method is still under
      discussion in the case of twins. Evidence-based data in favour of a general
      elective caesarean section are lacking but prospective randomized study results
      on this subject are expected. The organization of the clinic is essential for the
      safety of twins during vaginal delivery. The prerequisites for the vaginal
      delivery of twins and its management under various conditions are discussed in
      light of the literature.

PMID- 17440268
TI  - [Giving birth in the water: experience after 1,825 water deliveries.
      Retrospective descriptive comparison of water birth and traditional delivery
      methods].
AB  - OBJECTIVE: We reviewed 1,825 water births at a single institution over a 9-year
      period. METHODS: We compared 830 primipara deliveries in water with 424 primipara
      deliveries in the traditional bed and 136 on the delivery stool. We also
      evaluated the duration of labour, arterial cord blood pH and base excess in the
      primiparae, and perineal trauma, shoulder dystocia and deliveries after preceding
      caesarean section as well as rates of neonatal infection in all the 1,825 water
      births. RESULTS: The duration of the first stage of labour was significantly
      shorter with water births than with the other delivery positions. The episiotomy
      rate for all water births was found to be much lower compared to deliveries
      carried out in the bed or on the birthing stool. The rate of perineal tears was
      similar. There were no differences in the duration of the second stage, arterial
      cord blood pH and base excess. No woman using the water birth method required
      analgesics. There were 3 shoulder dystocias with water births. Sixty-eight women
      delivered in water after a preceding caesarean section. CONCLUSION: Water births
      appears to be associated with a significantly shorter first stage of labour, a
      lower episiotomy rate and reduced analgesic requirements when compared with other
      delivery positions. If women are selected appropriately, water birth appears to
      be safe for both the mother and neonate.

PMID- 17440269
TI  - [Comparison of the ThinPrep monolayer technique and conventional cervical Pap
      smears in a high-risk population using the Munich II nomenclature].
AB  - OBJECTIVE: In this prospective study using the Munich II nomenclature for
      cervical cytology. Pap smear results obtained by the ThinPrep monolayer technique
      and those obtained by the conventional method were compared. METHODS: Pap smears
      were obtained from 1,000 women using an Ayre spatula/endocervical brush
      combination. Following transfer of the cell sample onto a slide, the same
      collection devices were rinsed in a liquid medium and processed using ThinPrep
      2000 processor (split-sample technique). RESULTS: Specimen inadequacies due to
      drying artefacts, cell overlap or low number of epithelial cells were rare with
      both methods without any significant differences. However, ThinPrep slides were
      significantly less often compromised by red or white blood cells or by cytolysis.
      In contrast, endocervical cells were missing in 11.6% of slides compared to only
      2.3% in conventional Pap smears. ThinPrep yielded results of unknown significance
      (Pap III) significantly less often (4.2 vs 6.3%). CONCLUSIONS: ThinPrep slides
      are less frequently compromised by blood components or cytolysis. Inconclusive
      results of Pap III are slightly less frequent when using ThinPrep. However, there
      is a significant percentage of slides lacking the endocervical component. Using a
      combination of spatula and cytobrush, this may not necessarily be due to non
      representative cell sampling.

PMID- 17440270
TI  - [Diagnosis and management of vulvar intraepithelial neoplasias and invasive
      vulvar cancers].
AB  - OBJECTIVE: Update on the diagnosis and management of vulvar intraepithelial
      neoplasia (VIN) and vulvar carcinoma. METHOD: Review of the literature. RESULTS:
      The classification of VIN is leaning towards the development of two distinct
      anatomoclinical models. VIN of the usual type and of a differentiated type. New
      forms of treatment of preinvasive lesions that are less traumatic and as
      efficient will have to be evaluated in the future such as immunomodulators and
      photodynamic therapy. The invasive carcinoma is generally rapidly symptomatic and
      visible; however, more than one third of patients are still diagnosed at an
      advanced stage. New therapeutic alternatives are being examined such as the
      sentinel lymph node in early stages and the preoperative radiochemotherapy in
      advanced stages. CONCLUSIONS: VIN and vulvar cancer need specialized treatment
      which may be mutilating, despite the fact that therapeutic options are well
      defined today and tend towards less aggressive surgery.

PMID- 17440271
TI  - [Recommendations for hormonal contraception. 36th Professional Meeting of the
      "Zurich Discussion Group", April 2006].

PMID- 17440272
TI  - [Recommendations for 3 D ultrasound in pregnancy. Expert correspondence no. 17 of
      29 December 2006]].

PMID- 17440273
TI  - [Vaccination against human papillomaviridae. Expert correspondence no. 18 of 29
      December 2006].

PMID- 17440274
TI  - [Prevention of neonatal infection with Streptococcus Group B. Expert
      correspondence no. 19 of 29th December 2006].

PMID- 17440275
TI  - Inflammation in dry age-related macular degeneration.
AB  - PURPOSE: To summarize the current information regarding the role of immune and
      inflammatory response in the pathogenesis of dry age-related macular degeneration
      (ARMD). METHODS: A Pubmed search was conducted of the period January 1999 to
      2005. Relevant information in the literature on the role of inflammation in early
      dry ARMD was reviewed. RESULTS: Some important evidence for inflammation in early
      ARMD consists in the isolation of immunoglobulins, complement proteins, cytokines
      and activated microglia, in retinal pigment epithelium (RPE) cells and drusen.
      Pivotal mechanisms in early ARMD include the accumulation of debris and proteins
      along the RPE surface, followed by immune-complex deposition and complement
      activation. In contrast, the role of other plasma enzymes such as kallikrein
      kinin-bradykinin, the Hageman factor, peptides and coagulation proteins in drusen
      formation and ARMD has yet to be determined. CONCLUSION: A clear role for
      inflammatory mediators and cells has been established in recent years. Future
      studies should elucidate further mechanisms in ARMD development.

PMID- 17440276
TI  - Topical bromfenac sodium for long-term management of vernal keratoconjunctivitis.
AB  - BACKGROUND/AIMS: We evaluated the efficacy and safety of long-term management of
      patients with vernal keratoconjunctivitis (VKC) with bromfenac sodium eye drops
      in combination with corticosteroids and anti-allergic eye drops. METHODS: Twenty
      two patients with VKC were randomly assigned to receive two test eye drops,
      either bromfenac sodium 0.1% (group A) or placebo eye drops (normal saline; group
      B) for a mean observation period of 20.9 months. Topical corticosteroids and mast
      cell stabilizers were continued during the observation period. RESULTS: The mean
      2-year recurrence rate was 90.9% in group A and 11.3% in group B, with a
      significant difference. No serious side effect was observed in group A.
      CONCLUSION: These results suggest that bromfenac sodium eye drops can be used as
      baseline local treatment in patients with VKC.

PMID- 17440277
TI  - Effects of vitamin e, pentoxifylline and aprotinin on light-induced retinal
      injury.
AB  - PURPOSE: A considerable amount of clinical and experimental evidence exists
      suggesting the involvement of reactive oxygen species (ROS) in the etiology of
      light-induced retinal injury. The aim of this study was to investigate the
      protective role of vitamin E, pentoxifylline (PTX) and aprotinin against light
      induced retinal injury in guinea pigs. METHODS: Thirty adult male guinea pigs
      were divided into 5 groups of 6 animals each. The first group was used as
      control. The guinea pigs were kept in cyclic light for 2 weeks before the
      experiments. The animals were maintained in 12-hour light-dark cycles, before and
      after exposure to intense white fluorescent light, for as long as 12 h and then
      returned to cyclic light. Groups 3-5 received intraperitoneal injections of
      vitamin E, PTX and aprotinin, respectively. One eye of each animal was selected
      for histopathological evaluation and the other for biochemical assay. Retinal
      malondialdehyde (MDA) levels and the thickness of the outer nuclear layers were
      measured. RESULTS: The compounds had the following relationships: vitamin E more
      than PTX more than aprotinin in preventing light-induced retinal damage. All 3
      gave significant protection against the formation of MDA. Retinas of all 3
      treatment groups had been protected from light-induced injury. CONCLUSION: The
      intraperitoneal vitamin E, PTX and aprotinin supplementations may strengthen the
      antioxidant defense system because of decreased ROS, and these agents may play a
      role in treating light-induced retinal injury.

PMID- 17440278
TI  - Changes in higher order aberrations and contrast sensitivity after implantation
      of a phakic artisan intraocular lens.
AB  - PURPOSE: To evaluate higher-order aberrations (HOAs) and contrast sensitivity
      (CS), and investigate their relationship, after implantation of a phakic Artisan
      intraocular lens (IOL) for high myopia. METHODS: A prospective study including 25
      eyes of 15 patients with high myopia (greater than -8.00 D) who underwent phakic
      Artisan IOL implantation was carried out. Uncorrected visual acuity (UCVA), best
      corrected visual acuity, manifest refraction, and pupil diameter were measured at
      baseline and at 1 and 3 months postoperatively. HOAs were measured by Wavescan(R)
      (VISX Inc., Santa Clara, Calif., USA) from the 3.0 mm pupil entrance, and CS was
      measured using the VCTS(R) 6500 (Vistech consultants, Inc., Dayton, Ohio, USA)
      under photopic conditions. The area under the log contrast sensitivity function
      (AULCSF), defined as the integration of the fitted third order polynomial of the
      log CS units between the fixed limits of 0.18 (1.5 CPD) and 1.25 (18 CPD) on the
      log spatial frequency scale, was calculated. RESULTS: UCVA LogMAR improved from
      1.58 at baseline to 0.22 at 3 months, and spherical equivalent refraction was 
      0.77 +/- 0.34 D at 3 months. The total HOAs had increased slightly at 1 month. CS
      had decreased significantly at all cycles per degree (p < 0.05) at 1 month, but
      returned to baseline values at 3 months. Postoperative AULCSF did not correlate
      with total HOAs under photopic conditions, but correlated with UCVA LogMAR at 1
      month (p = 0.037). CONCLUSIONS: Phakic Artisan IOL implantation for the
      correction of high myopia resulted in a small increase of HOAs under photopic
      conditions. At 1 month, CS was decreased, but returned to baseline at 3 months
      under photopic conditions. Postoperative AULCSF did not correlate with total HOAs
      at 1 month.

PMID- 17440279
TI  - Primary ocular natural killer/T-cell lymphomas: clinicopathologic features and
      diagnosis.
AB  - PURPOSE: Primary ocular natural killer/T-cell lymphoma (NKTL) is rare. This study
      aims to characterize the clinical manifestations, diagnosis and treatment methods
      of primary ocular NKTL. METHODS: Clinical data of seven patients with ocular NKTL
      from 1982 to 2004 were collected. A morphologic, immunohistochemical and
      molecular analysis was undertaken. RESULTS: Clinical manifestations and computed
      tomography of the patients were typical. LCA CD56 CD3epsilon Ki-67 granzyme B
      (GrB) and T-cell intracellular antigen-1(TIA-1) were mostly positive. Clonal T
      cell-receptor gene rearrangements of five patients showed negative findings, and
      the detection of Epstein-Barr virus showed positive. All patients died 5 months
      to 28 months after presentation. CONCLUSION: Ocular NKTL is a highly aggressive
      clinical course with poor prognosis. The diagnosis relies on clinicopathologic
      findings.

PMID- 17440280
TI  - Retinal blood flow autoregulation after dynamic exercise in healthy young
      subjects.
AB  - PURPOSE: To evaluate the retinal blood flow before and after the increase in
      systemic blood pressure to assess the autoregulation in healthy young subjects.
      METHODS: Twenty eyes of 20 healthy volunteers were examined. The retinal blood
      flow was assessed by a Heidelberg retina flowmeter (HRF), while the systemic
      pressure was assessed by a portable electronic sphygmomanometer. Furthermore
      intraocular pressure (IOP) was always measured by a Goldmann tonometer
      immediately after HRF assessments. All measurements of physiological and flow
      parameters were performed with the subjects seated at rest and then immediately
      after stair climbing. RESULTS: The IOP decreased significantly after dynamic
      exercise, while the heart rate and the systemic artery pressure increased
      significantly. At the baseline, the mean retinal blood flow was 276.8 +/- 80.7
      arbitrary units (AU) in the superotemporal area, 243.4 +/- 63.68 AU in the
      superonasal area, 258.2 +/- 67.37 AU in the inferotemporal area and 243.9 +/-
      72.24 AU in the inferonasal area. After dynamic exercise the mean retinal blood
      flow was 249.8 +/- 86.78 AU in the superotemporal area, 248.7 +/- 63.87 AU in the
      superonasal area, 245.4 +/- 83.85 AU in the inferotemporal area and 228.8 +/-
      62.53 AU in the inferonasal area. No significant change in retinal blood flow was
      found. CONCLUSION: Our data support the hypothesis that in normal subjects
      autoregulation is sufficient to compensate the increase in blood pressure and
      maintain a stable retinal blood flow after exercise.

PMID- 17440281
TI  - Nerve fibre layer analysis with GDx with a variable corneal compensator in
      patients with multiple sclerosis.
AB  - PURPOSE: To evaluate the ability of GDx with variable corneal compensator (VCC)
      compared to visual-evoked potentials (VEPs) and standard automated perimetry
      (SAP) in the detection of early optic nerve damage in patients with multiple
      sclerosis (MS). METHODS: 46 eyes of 23 MS patients were included. Ten of them had
      a history of acute retrobulbar optic neuritis. A control group of 20 normal
      subjects was also included. All subjects underwent a complete ophthalmological
      examination and testing with SAP, GDx VCC and VEPs. RESULTS: 19 eyes (41.3%) were
      abnormal with GDx VCC compared to 38 eyes (82.6%) with SAP and 31 (64.4%) with
      VEPs. In the optic neuritis group, 9 eyes (69.2%) had optic nerve pallor; SAP was
      abnormal in 8 of these eyes (61.5%) while VEPs and GDx VCC were abnormal in 6
      eyes (46.1%). 2/20 eyes (10.0%) in the control group gave a false-positive
      abnormal result with SAP. GDx VCC and VEP were normal for all the eyes in the
      control group. CONCLUSIONS: GDx VCC is less able to detect early defects in MS
      patients compared to the currently used standard techniques of SAP and VEPs.

PMID- 17440282
TI  - The influence of low to moderate myopia on retinal nerve fiber layer as assessed
      by scanning laser polarimetry with variable corneal compensator.
AB  - PURPOSE: To evaluate the influence of different degrees of myopia on retinal
      nerve fiber layer (RNFL) as measured by scanning laser polarimetry (SLP) with
      variable corneal compensator (VCC) in healthy eyes. METHODS: One hundred and
      seventy-four healthy age-matched subjects with low to high myopic and emmetropic
      eyes underwent RNFL measurement by means of GDxVCC. The GDx parameters included
      in the analysis were: Temporal-superior-nasal-inferior thickness (TSNIT) average,
      Superior average, Inferior average, TSNIT standard deviation, Inter-eye symmetry,
      NFI, Symmetry, Superior ratio, Inferior ratio, Superior/nasal, Maximum
      modulation, Superior maximum, Inferior maximum, Ellipse modulation, Normalized
      superior area, Normalized inferior area, Ellipse standard deviation, Ellipse
      average. The mean value of each SLP parameter of myopic eyes was compared with
      the mean value of the same parameter of emmetropic eyes. RESULTS: Mean myopia was
      3.9 +/- 1.5 dpt (range: -2 to -8.25 dpt). TNSIT average was higher in myopic
      group (p = 0.0111), together with Superior average (p = 0.0244), Symmetry (p <
      0.0001) and Ellipse average (p = 0.0111). Two ratio parameters, Superior ratio
      and Inferior ratio, were higher in emmetropic eyes (p = 0.0179 in both cases). In
      both the myopic and the emmetropic group, all the SLP assessments of the RNFL
      fell within the normal range, according to the GDx database. CONCLUSIONS: Low to
      high myopia is not related to clinically relevant variations of SLP parameters,
      as assessed with GDx-VCC.

PMID- 17440283
TI  - Discriminating ability of Humphrey matrix perimetry in early glaucoma patients.
AB  - PURPOSE: To determine the discriminating ability of some parameters provided by
      Humphrey Matrix perimetry for early glaucoma detection. METHODS: A prospective
      cross-sectional study was performed. Sixty-five primary open-angle glaucoma
      patients with early-stage visual field defects on standard automated perimetry
      (mean deviation = -1.98 +/- 1.93 dB) and 56 healthy subjects were included. All
      subjects performed the Humphrey Matrix perimetry with a threshold 30-2 strategy.
      The receiver operating characteristic (ROC) curve was constructed for each
      parameter and calculated the area under the ROC curve (AUC) to seek the best
      discriminating parameter for early glaucoma detection. RESULTS: The AUCs of
      Humphrey Matrix perimetry with the mean deviation, pattern standard deviation,
      Glaucoma Hemifield Test, number of points that have a p < 5% in pattern deviation
      plot (PDP) and number of points that have a p < 1% in PDP were 0.795, 0.808,
      0.689, 0.985 and 0.946, respectively. CONCLUSION: Humphrey Matrix perimetry
      allowed accurate discrimination between normal and early glaucomatous eyes. The
      number of points that had a p < 5% in PDP was the best discriminating parameter
      for early glaucoma detection using Humphrey Matrix perimetry.

PMID- 17440284
TI  - Intraocular extension of conjunctival squamous cell carcinoma.
AB  - Conjunctival squamous carcinoma, which is regarded as a low-grade malignancy,
      usually originates at the limbus. Most cases remain superficial to the sclera.
      Intraocular invasion is rarely reported. We describe a woman misdiagnosed as
      conjunctivitis and pterygium before a clinical diagnosis of conjunctival squamous
      cell carcinoma. The diagnosis was made by histopathological examination of the
      biopsy specimen. Examination revealed an elevated mass on the nasal limbus
      extending intraocularly. White flaky mass occupied approximately 3/7 space of the
      anterior chamber. Exenteration was performed for control of local lesion.
      Histopathologic analysis confirmed that intraocular involvement occurs through
      the emissary vessels near the area of limbus. The case highlights the need for
      accurate diagnosis and prompt intervention. A brief review of the clinical and
      histopathologic features of conjunctival squamous cell carcinoma is also
      presented.

PMID- 17440285
TI  - A case of lacrimal gland dirofilariasis.
AB  - A patient with a diagnosis of chronic and idiopathic unilateral dacryoadenitis
      was submitted to our clinic for diagnostic reasons from a regional hospital.
      Within a period of 1 year, this was the second onset of a swelling in the region
      of the lacrimal gland which - unlike the first time - showed resistance to
      antibiotic treatment. The patient's general and ophthalmic condition was good,
      and his only complaint was of cosmetic nature because of the disfiguring swelling
      in the lateral part of the left upper eyelid. Basic laboratory findings showed no
      abnormalities and radiographic imaging showed enlargement of the left lacrimal
      gland without bony destruction. Guided by epidemiological data for noninfectious
      dacryoadenitis we decided to perform excisional biopsy of the left lacrimal
      gland. To our surprise, the pathologist verified the presence of a worm of the
      genus Dirofilaria, which is, to the best of our knowledge, the second reported
      case of lacrimal gland dirofilariasis in the literature and the second reported
      case of such a disease in Croatia.

PMID- 17440286
TI  - The use of the orbital septum in inferior palpebral reconstruction: the pocket
      technique.
AB  - BACKGROUND: Surgery involving massive inferior palpebral demolition often imposes
      the use of free flaps for the reconstruction of the anterior and posterior
      lamellae. PURPOSE: We describe a surgical technique which provides for the use of
      a homologous pedunculated elastic flap on which we wrap the free flap as in a
      pocket, in order to guarantee that the free flap itself takes root better.
      METHODS: A study of 10 patients admitted to our hospitals for massive inferior
      palpebral demolition surgery between March 2002 and November 2004 was undertaken,
      and clinical records (age, sex, involved site of lesions, surgery technique) were
      accurately noted: in all patients we performed the 'pocket technique'. RESULTS:
      The pocket technique has encouraged optimal attachment of the implanted free
      tissue, in absence of necrotic phenomena or tissue extrusion. CONCLUSIONS:
      Reconstructive surgery of the inferior eyelid avails itself of consolidated
      techniques. In case of extreme tissue reduction, the variation we wish to suggest
      is simple to understand and easy to perform, significantly reducing inflammatory
      reaction and/or post-surgical rejection, allowing excellent aesthetic results.

PMID- 17440287
TI  - Standardized assessment of psychopathology by relatives of mentally disordered
      patients. Preliminary results of using the positive and negative syndrome scale
      to compare schizophrenic and affective disorders.
AB  - BACKGROUND: For optimizing the validity of diagnoses of mental disorders, several
      sources of information should be used to assess psychopathological symptoms.
      Among these are relatives of patients with mental illness. The very low number of
      empirical studies examining the assessment of psychopathology by relatives of
      adult, nondemented mentally ill patients stands in significant contrast to the
      clinical importance of this source of information, however. SAMPLING AND METHODS:
      Using the Positive and Negative Syndrome Scale (PANSS), researchers asked 163
      relatives of patients with the main clinical ICD-10 diagnosis of schizophrenic,
      recurrent depressive or bipolar disorders to rate the current symptoms of the
      patients at the time of outpatient community-oriented treatment. RESULTS: On
      average, severity of symptoms was rated as absent or minimal, although anxiety,
      depression and passive/apathetic social as well as emotional withdrawal, motor
      retardation, poor attention, and disturbance of volition were clearly rated above
      the PANSS mean total score for all patients. A six-factor structure identified by
      factor analysis better illustrates the significant differences in the assessments
      of the three main diagnostic groups than the three established PANSS scales. With
      the exception of 'problematic social behavior', differences among the diagnostic
      groups appeared in all factors and were particularly pronounced for 'delusional
      beliefs' and 'motor impairments'. CONCLUSIONS: The results of this study showed
      that the use of standardized instruments such as PANSS for the assessment of
      psychopathology by relatives is not only practical, but produces adequately
      reliable results. The use of PANSS for this purpose, however, requires
      interviewing of relatives by trained experts able to explain technical terms.
      Because this study did not sufficiently explore the validity of this approach,
      further research on this specific issue is urgently needed and should, for
      example, assess the concordance of ratings between professionals and relatives as
      well as correlation with suitable external criteria.

PMID- 17440288
TI  - Metacognition and reflexivity in patients with schizophrenia.
AB  - BACKGROUND: Many patients with schizophrenia demonstrate a lack of insight into
      their disorder and often do not complain about their cognitive impairments. This
      might be due to generally reduced metacognitive abilities. SAMPLING AND METHODS:
      Twenty-seven patients with a DSM IV diagnosis of schizophrenia and 19 healthy
      control subjects performed 2 separate tasks tapping into metacognitive functions.
      In the first experiment the participants encoded words. In the following
      recognition part they judged their level of subjective confidence in the
      correctness of their answer. In the second experiment reaction time was measured,
      whilst judgments were made about personality trait adjectives describing the
      subjects themselves or other familiar people. RESULTS: Although the recognition
      rate in the first experiment was equal between the groups, the patients showed a
      significantly reduced ability to correctly judge their memory performance. There
      was no correlation between metamemory and psychopathology nor insight measures.
      The patients further needed significantly more time to characterize themselves
      compared to the healthy participants. The response rates for self
      characterization correlated with the ability to recognize symptoms as part of a
      disorder but did not correlate with psychopathology. CONCLUSIONS: Metacognitive
      faculties seem to be, at least in part, a separable cognitive entity. Patients
      with schizophrenia demonstrate impaired metacognitive capacities, independent of
      current symptoms or memory performance.

PMID- 17440289
TI  - Clinical, psychological and personality features related to age of onset of
      anorexia nervosa.
AB  - BACKGROUND: To investigate the relationship between age of onset and clinical and
      personality features of patients with anorexia nervosa (AN). SAMPLING AND METHOD:
      We assessed 250 outpatients with AN with the Temperament and Character Inventory,
      the Eating Disorder Inventory 2, the Beck Depression Inventory and the Body Shape
      Questionnaire. The patients were subdivided into 3 groups: early (n=73),
      intermediate (n=96) and late onset (n=81), based on age of onset of symptoms.
      RESULTS: The early-onset group shows higher body dissatisfaction, maturity fear,
      impulsivity and asceticism than the other 2 groups. This group shows a greater
      character fragility, as described in particular by a lower self-directedness,
      than the other 2 groups. CONCLUSIONS: Even several years after the onset of the
      disorder, early-onset subjects affected by AN seem characterized by a more
      disturbed personality, with a higher body dissatisfaction than late-onset
      subjects affected by AN and a pursuit of thinness based on an ascetic drive.

PMID- 17440290
TI  - Innovative solutions: a plurality of vision--integrating the chaplain into the
      critical care unit.
AB  - Banner Good Samaritan Medical Center is a 650-bed quarternary care facility
      located in the Southwestern United States. It contains 12 intensive care units
      (ICUs) and experience a high patient acuity as a result of being a referral
      center for Arizona. The palliative care nurse practitioner and ICU clinical nurse
      specialist collaborated with the chaplain to entrance his visibility in the ICUs
      and to incorporate the philosophy of spiritual care assessments in the ICU.

PMID- 17440291
TI  - Caring for the incarcerated in the intensive care unit.
AB  - In the United States, jail and prison populations continue to be on the rise. In
      1976, the US Supreme Court mandated correctional facilities to provide necessary
      medical care to all incarcerated individuals. Often, this population is
      frequently associated with chronic illnesses and accidental injuries that require
      admission to the intensive care unit. This article will be a case presentation of
      a critically ill patient and a brief discussion of safe and effective
      interventions of the incarcerated patient in the intensive care unit.

PMID- 17440292
TI  - Promotion of family integrity in the acute care setting: a review of the
      literature.
AB  - The acute illness of 1 family member can then negatively affect all family
      members and lead to the disruption of family functioning and integrity. During
      the patient's hospitalization, nurses are in a key position to support family
      members, maintain family integrity, and ready them for assuming the role of
      caretaker during the patient's recovery and management of health at home. This
      article reviews current research findings that provide empirical support for
      activities that promote family integrity. Strategies for nurses to support family
      members during the hospitalization of an adult family member and suggestions for
      future research are provided.

PMID- 17440295
TI  - A blueprint for developing an undergraduate critical care nursing course.
AB  - The purpose of this article is to provide a blueprint for nursing programs to
      create or modify baccalaureate critical care courses. The benefits of providing a
      critical care course include offering students an in-depth experience in a
      specialty area, reinforcing previously learned medical-surgical content, and
      improving students' critical thinking skills. In addition, hospitals are given
      the opportunity to interact with students while also recruiting them into a high
      demand area.

PMID- 17440296
TI  - Clinical research and the development of new devices: considerations for nurses.
AB  - New investigational drugs and devices are commonly used in critically ill
      patients. The development of new drugs and the role of the critical care nurse
      caring for subjects in clinical trials are crucial to the success of the research
      process. The purpose of this article is to discuss the Food and Drug
      Administration's regulatory approval process for significant risk investigational
      devices.

PMID- 17440298
TI  - Blood pressure and risks of vascular complications after percutaneous coronary
      intervention.
AB  - Evidence-based protocols are needed for care of the nearly 1,000,000 patients in
      the United States who undergo percutaneous coronary interventional procedures.
      This article describes a case-matched control study of 300 patients undergoing
      percutaneous coronary intervention in which specific demographic, physician
      sensitive, and nurse-sensitive factors were tested to determine their relative
      contribution to the incidence of vascular complications. Findings included that
      patients with a mean systolic blood pressure of 160 mm Hg or higher were 8 times
      more likely to have vascular complications (P < .001). Patients receiving heparin
      (with and without glycoprotein IIb/IIIa inhibitors) versus bivalirudin were 3
      times more likely to have vascular complications (P = .008). Patients with
      hemostasis by AngioSeal and those with a history of hypertension were 77% (P
      =.031) and 61% (P = .005), respectively, less likely to have complications.

PMID- 17440305
TI  - The voice of truth.

PMID- 17440306
TI  - Women with irritable bowel syndrome and their perception of a good quality of
      life.
AB  - Irritable bowel syndrome has a negative impact on a person's quality of life, but
      only a few existing studies have been based on patients' own perceptions. This
      study therefore aimed to collect information on the view of female patients with
      irritable bowel syndrome regarding what constitutes a good quality of life for
      them and to create a healthcare model for these patients. For the study, 30 women
      with irritable bowel syndrome (median age, 38.5 years; range, 20-65 years)
      responded in writing to a single, all-inclusive question: "What is your
      perception of a good quality of life?" When the questionnaires were returned,
      there was time for a short dialogue, and notes of the conversations were made.
      Data were analyzed qualitatively according to Burnard's method of thematic
      content analysis. The answers also were counted and thereby quantified. The
      women's perception of a good quality of life could be divided into five
      categories: (a) physical and mental health, (b) social well-being, (c) welfare,
      (d) strength and energy, and (e) self-fulfillment. According to the results, a
      healthcare model for patients with irritable bowel syndrome should include four
      main areas: (a) treatment of the patient's symptoms, (b) confirmation of the
      patient, (c) confirmation of the diagnosis, and (d) instruction for the patient.
      The healthcare model should be focused on the primary care level and should
      include a longitudinal plan of healthcare that also describes the secondary care
      level.

PMID- 17440307
TI  - A validity and reliability study investigating the Turkish version of the Infant
      Colic Scale.
AB  - The Infant Colic Scale is used to diagnose colic and to determine factors that
      cause colic. This study aimed to establish the validity and reliability of the
      Infant Colic Scale for the Turkish population. The research sample included
      mothers (N = 110) of 132 infants with colic registered at three public health
      clinics in the Denizli province. Language validity, content validity, and
      construct validity were examined. On the basis of the Infant Colic Scale's
      internal consistency reliability analysis, three items were removed. Factor
      analysis resulted in five subscales. The Cronbach's alpha coefficients were .55
      to .89 for the subscales, and .73 for the total scale. The scale's test-retest
      reliability was .65. The Infant Colic Scale was found to be a valid and reliable
      measurement tool for the Turkish population.

PMID- 17440309
TI  - A comprehensive guide to patient-focused management strategies for Crohn disease.
AB  - In Crohn disease, a vigorous inflammatory cascade is caused by the overactivation
      of helper T-cells in the gastrointestinal system. The results of this
      inflammation manifest themselves as the symptoms of Crohn disease. This article
      describes the pathophysiology of Crohn disease as well as multiple pharmacologic
      and nonpharmacologic interventions that may assist patients with Crohn disease in
      preventing exacerbations and maintaining longer remissions.

PMID- 17440313
TI  - Endoscopic shuffling, infection control, and the clinical practice of push
      enteroscopy.
AB  - Failure to identify and diagnose the site and cause of obscure bleeding or some
      other gastrointestinal disorder may be an indication for push enteroscopy. During
      this procedure, a long, narrow, flexible gastrointestinal endoscope, known as a
      push enteroscope, is advanced into the upper gastrointestinal tract to examine
      and evaluate the proximal section (first one third) of the small bowel. Because
      of limited funding and inadequate instrument availability, some gastrointestinal
      endoscopy units may perform this procedure using a colonoscope instead of a push
      enteroscope. Although not specifically designed for push enteroscopy,
      colonoscopes are less expensive than push enteroscopes and readily available for
      clinical use in virtually every gastrointestinal endoscopy unit. The use of a
      colonoscope or other lower gastrointestinal endoscope to perform push enteroscopy
      or another upper gastrointestinal procedure (or the use of an upper
      gastrointestinal endoscope to perform a lower gastrointestinal procedure) is
      defined in this article as endoscopic shuffling. Although it is arguably
      efficient and cost effective (and in some instances may improve clinical
      outcomes), endoscopic shuffling raises a number of economic, legal, medical, and
      ethical questions and concerns, several of which are discussed in this article,
      with a particular focus on infection control.

PMID- 17440311
TI  - Primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown
      origin characterized by progressive inflammation, destruction, and fibrosis of
      the intrahepatic and extrahepatic bile ducts. The disease leads to obliteration
      of intrahepatic bile ducts and to biliary cirrhosis, end-stage liver disease, and
      portal hypertension. Primary sclerosing cholangitis commonly occurs in the
      presence of inflammatory bowel disease. Its exact etiology remains unknown. As a
      result, there is no existing effective medical management to delay or modify the
      progression of the disease. Ursodeoxycholic acid, the most well-studied drug for
      primary sclerosing cholangitis, has demonstrated promising results when used in
      combination with an immunosuppressant or antibiotic. To date, liver
      transplantation remains the only confirmed long-term treatment of primary
      sclerosing cholangitis, which now accounts for 6% of adult and 1% of pediatric
      liver transplantations in the United States. Primary sclerosing cholangitis
      represents an important liver disease with major morbidity and mortality.

PMID- 17440314
TI  - Emergent cases.

PMID- 17440315
TI  - Cultural competence and patient advocacy: the new challenge for nurses.

PMID- 17440316
TI  - Supporting bedside nursing research and evidence-based practice.

PMID- 17440317
TI  - Commentary on clinical applications of argon plasma coagulation in endoscopy.

PMID- 17440319
TI  - A patient who made a difference.

PMID- 17440320
TI  - Measurement tool requirements.

PMID- 17440321
TI  - Effect of quench on alpha/beta pulse shape discrimination of liquid scintillation
      cocktails.
AB  - The objectives of this paper are (1) to illustrate that knowledge of the external
      quench parameter is insufficient to properly setup a pulse shape discriminating
      liquid scintillation counter (LSC) for quantitative measurement, (2) to
      illustrate dependence on pulse shape discrimination on the radionuclide (more
      than just radiation and energy), and (3) to compare the pulse shape
      discrimination (PSD) of two commercial instruments. The effects various quenching
      agents, liquid scintillation cocktails, radionuclides, and LSCs have on
      alpha/beta pulse shape discriminating liquid scintillation counting were
      quantified. Alpha emitting radionuclides (239)Pu and (241)Am and beta emitter
      (90)Sr/(90)Y were investigated to quantify the nuclide dependence on alpha/beta
      pulse shape discrimination. Also, chemical and color quenching agents,
      nitromethane, nitric acid, and yellow dye impact on alpha/beta pulse shape
      discrimination using PerkinElmer Optiphase "HiSafe" 2 and 3, and Ultima Gold AB
      liquid scintillation cocktails were determined. The prepared samples were counted
      on the PerkinElmer Wallac WinSpectral 1414 alpha/beta pulse shape discriminating
      LSC. It was found that for the same level of quench, as measured by the external
      quench parameter, different quench agents influenced the pulse shape
      discrimination and the pulse shape discrimination parameters differently. The
      radionuclide also affects alpha/beta pulse shape discrimination. By comparison
      with the PerkinElmer Tri-carb 3150 TR/AB, the Wallac 1414 exhibited better pulse
      shape discrimination capability under the same experimental conditions.

PMID- 17440322
TI  - Exercise Maritime Response (EXMR): lessons learned for population monitoring and
      communications.
AB  - Exercise Maritime Response was the third in a series of four emergency response
      exercises sponsored by the Chemical, Biological, Radiological and Nuclear
      Research and Technology Initiative. It was designed to test the Canadian Federal,
      Provincial and Municipal response to a terrorist attack using radioactive
      materials. The complexity of this exercise had been increased over previous
      exercises to now include simulated contaminated members of the public. This paper
      summarizes the experiences, and the lessons learned, of the Health Canada (HC)
      team. The largest issues identified by the HC team were: crowd control,
      insufficiency of staff to deal with surge capacity, and communications. The
      exercise did prove that the population monitoring equipment worked well and that
      small amounts of radioactivity were easily identified and quantified to within
      20% of their true value.

PMID- 17440323
TI  - Field and bioassay indicators for internal dose intervention therapy.
AB  - Guidance is presented that is used at the U.S. Department of Energy Hanford Site
      to identify the potential need for medical intervention in response to intakes of
      radioactivity. The guidance, based on ICRP Publication 30 models and committed
      effective dose equivalents of 20 mSv and 200 mSv, is expressed as numerical
      workplace measurements and derived first-day bioassay results for large intakes.
      It is used by facility radiation protection staff and on-call dosimetry support
      staff during the first few days following an intake.

PMID- 17440324
TI  - Decontamination and deactivation of the power burst facility at the Idaho
      National Laboratory.
AB  - Successful decontamination and deactivation of the Power Burst Facility located
      at the Idaho National Laboratory was accomplished through the use of extensive
      planning, job sequencing, engineering controls, continuous radiological support,
      and the use of a dedicated group of experienced workers. Activities included the
      removal and disposal of irradiated fuel, miscellaneous reactor components and
      debris stored in the canal, removal and disposition of a 15.6 curie Pu:Be start
      up source, removal of an irradiated in-pile tube, and the removal of
      approximately 220,000 pounds of lead that was used as shielding primarily in
      Cubicle 13. The canal and reactor vessel were drained and water was transferred
      to an evaporation tank adjacent to the facility. The canal was decontaminated
      using underwater divers, and epoxy was affixed to the interior surfaces of the
      canal to contain loose contamination. The support structures and concrete or
      steel frame walls that form the confinement were left in place. The reactor core
      was left in place and a carbon steel shielding plate was placed over the reactor
      core to reduce radiation levels. All low-level waste and mixed low level waste
      generated as a result of the work activities was characterized and disposed.

PMID- 17440325
TI  - RSO Interview with Bill Tuttle.

PMID- 17440326
TI  - Measurement and control of the air contamination generated in a medical cyclotron
      facility for PET radiopharmaceuticals.
AB  - The aim of this paper is to report the data concerning the contamination of the
      exhausted air from the hot cells dedicated to the large-scale synthesis of
      positron emission tomography (PET) radiopharmaceuticals. Two cyclotrons are
      currently operating in Ospedale San Raffaele for the routine production of C and
      F. They are linked with four radiochemistry laboratories by means of shielded
      radioisotope delivery lines. The above labs are dedicated both to the large scale
      preparation and to the research and development of PET radiopharmaceuticals. The
      department hosts four CT-PET scanners, which operate with a mean patient workload
      of 40 per day. Radiosyntheses are performed using automated modules located in 10
      hot cells. The air outlets are monitored online by a 2-inch NaI(Tl) counter in a
      Marinelli geometry counting volume. Contamination values up to 10(5) Bq L(-1)
      have been measured at the hot cell exit point during the synthesis. The
      corresponding concentrations at the point of release in atmosphere are largely
      above the threshold of 1.29 Bq L(-1), defined by national regulations as the
      limit for free environmental release. A shielded gas storage system controlled by
      a dedicated, customized software program has thus been installed to prevent the
      potentially hazardous release of gaseous radioactive contaminants. The system has
      allowed us to maintain the effective dose to neighboring population groups below
      the limit of 10 muSv y(-1).

PMID- 17440327
TI  - Simulation, design, and construction of a 137Cs irradiation facility.
AB  - Regulatory entities require that for any radiation facility the surrounding areas
      must be restricted unless the dose equivalent is less than 0.02 mSv in any one
      hour. Two Monte Carlo radiation transport simulation codes, MCNP5 and Mercurad,
      were used to design a facility to shield a 3.48 x 10(5) MBq 137Cs irradiator that
      meets these requirements. Simulations showed that the dose equivalent rates were
      below the legal limit for unrestricted access and the facility was constructed
      using available concrete block and student labor to minimize costs. To verify the
      accuracy of the Monte Carlo radiation transport codes, an ion chamber was used to
      characterize the facility. Ion chamber measurements in the actual, as-built
      irradiation facility showed that the Monte Carlo codes, MCNP5 and Mercurad,
      agreed by a factor of better than 6% and better than 11%, respectively.

PMID- 17440328
TI  - Risk ranking of LANL nuclear material storage containers for repackaging
      prioritization.
AB  - Safe handling and storage of nuclear material at U.S. Department of Energy
      facilities relies on the use of robust containers to prevent container breaches
      and subsequent worker contamination and uptake. The U.S. Department of Energy has
      no uniform requirements for packaging and storage of nuclear materials other than
      those declared excess and packaged to DOE-STD-3013-2000. This report describes a
      methodology for prioritizing a large inventory of nuclear material containers so
      that the highest risk containers are repackaged first. The methodology utilizes
      expert judgment to assign respirable fractions and reactivity factors to
      accountable levels of nuclear material at Los Alamos National Laboratory. A
      relative risk factor is assigned to each nuclear material container based on a
      calculated dose to a worker due to a failed container barrier and a calculated
      probability of container failure based on material reactivity and container age.
      This risk-based methodology is being applied at LANL to repackage the highest
      risk materials first and, thus, accelerate the reduction of risk to nuclear
      material handlers.

PMID- 17440329
TI  - Hair dosimetry following neutron irradiation.
AB  - Use of hair as a biological dosimeter of neutron exposure was proposed a few
      years ago. To date, the (32)S(n,p)(32)P reaction in hair with a threshold of 2.5
      MeV is the best choice to determine the fast neutron dose using body activation.
      This information is essential with regards to the heterogeneity of the neutron
      transfer to the organism. This is a very important parameter for individual dose
      reconstruction from the surface to the deeper tissues. This evaluation is
      essential to the adapted management of irradiated victims by specialized medical
      staff. Comparison exercises between clinical biochemistry laboratories from
      French sites (the CEA and COGEMA) and from the IRSN were carried out to validate
      the measurement of (32)P activity in hair and to improve the techniques used to
      perform this examination. Hair was placed on a phantom and was irradiated at
      different doses in the SILENE reactor (Valduc, France). Different parameters were
      tested: variation of hair type, minimum weight of hair sample, hair wash before
      measurement, delivery period of results, and different irradiation
      configurations. The results obtained in these comparison exercises by the
      different laboratories showed an excellent correlation. This allowed the
      assessment of a dose-activity relationship and confirmed the feasibility and the
      interest of (32)P measurement in hair following fast neutron irradiation.

PMID- 17440330
TI  - Rapid response teams: reducers of death. Find out how response teams save lives
      by rendering care to a patient before a cardiac or respiratory arrest occurs.

PMID- 17440331
TI  - Tighten up glycemic control. Aggressive insulin therapy in critical care settings
      is the latest method of reducing mortality rates.

PMID- 17440332
TI  - Take an evidence-based approach to treating acute lung injury. Recognize and
      promptly address ALI and ARDS to reduce substantial patient harm.

PMID- 17440333
TI  - Flash pulmonary edema: an unusual presentation during orthognathic surgery.

PMID- 17440334
TI  - The distally based sural flap.
AB  - LEARNING OBJECTIVES: After studying this article, the participant should be able
      to: (1) Describe the anatomy of the posterior lower leg as it is relevant to the
      distally based sural flap. (2) Describe the basic surgical technique of the
      distally based sural fasciocutaneous flap. (3) Understand the common
      complications associated with the sural flap and their approximate incidences in
      both a healthy and a multimorbid patient population. (4) Describe how skin,
      fascia, and muscle can be used to customize the sural flap for different
      purposes. (5) Understand the various modifications of the sural flap that have
      been described in the literature. SUMMARY: Over the past decade, the distally
      based sural flap has become increasingly used in reconstruction of the foot and
      lower leg. The rise in popularity of this flap has been paralleled by an increase
      in the number of cases, innovations, and technical refinements reported in the
      medical literature. This review summarizes the 79 publications in the English
      language literature on the subject of the distally based sural flap. The
      anatomical studies are summarized in a unified description of the relevant flap
      anatomy. The flap's indications and composition and a variety of modifications
      are described. Technical aspects are discussed and clinical insight to minimize
      complications is provided. In conclusion, the distally based sural flap offers an
      alternative to free tissue transfer for reconstruction of the lower extremity.

PMID- 17440335
TI  - Periareolar skin-sparing mastectomy and latissimus dorsi flap with biodimensional
      expander implant reconstruction: surgical planning, outcome, and complications.
AB  - BACKGROUND: Although use of the latissimus dorsi myocutaneous flap associated
      with the Biodimensional anatomical expander implant system (McGhan 150) is a
      reliable technique, little information has been available regarding clinical
      outcome following periareolar skin-sparing mastectomy reconstruction. The purpose
      of this study was to analyze the feasibility of the technique, surgical planning,
      and its outcome following skin-sparing mastectomy. METHODS: Thirty-two patients
      underwent immediate unilateral latissimus dorsi myocutaneous flap/Biodimensional
      anatomical expander implant system breast reconstruction. Mean follow-up was 18
      months. The technique was indicated in patients with small- or moderate-volume
      breasts with or without ptosis, in whom the use of abdominal flaps was precluded.
      Flap and donor-site complications were evaluated. Information on anesthetic
      results and patient satisfaction was collected. RESULTS: Seventy-two percent had
      tumors measuring 2 cm or less (T1) and 78 percent were stage 0 and I according to
      American Joint Committee on Cancer criteria. Breast skin complications occurred
      in 9.4 percent. Two patients presented small breast skin necrosis, and in one
      patient, a wound dehiscence was observed. Donor-site complications, all
      represented by seroma, occurred in 12.5 percent. The cosmetic result was
      considered good or very good in 84.4 percent, and the majority of patients were
      either very satisfied or satisfied. No local recurrences were observed. All
      complications except two were treated by conservative means. CONCLUSIONS: The
      latissimus dorsi myocutaneous flap/Biodimensional anatomical expander implant
      system is a simple and reliable technique for periareolar skin-sparing mastectomy
      reconstruction. Success depends on patient selection, coordinated planning with
      the oncologic surgeon, and careful intraoperative and postoperative management.

PMID- 17440337
TI  - Silsesquioxane nanocomposites as tissue implants.
AB  - BACKGROUND: Silicone implants are being used increasingly worldwide, especially
      in breast augmentation procedures. The most common morbidity observed is capsular
      contracture, which occurs in 15 percent of cases. To overcome this problem, the
      authors have developed a novel nanocomposite based on polyhedral oligomeric
      silsesquioxane-poly(carbonate-urea)urethane (POSS-PCU) for use as tissue
      implants. METHODS: These polymers were implanted in six healthy sheep (n = 6) for
      36 months and a siloxane served as the positive control. After explantation,
      these polymers were extracted, as was the surrounding capsule, if any. Attenuated
      total reflectance Fourier transform infrared spectroscopy analysis was performed
      to look for signs of surface degradation on the polymers and histopathologic and
      electron microscopic examinations were performed to study the interaction between
      the biomaterial and the host environment in greater detail. RESULTS: After
      implantation, the authors observed minimal inflammation of the nanocomposite
      within the sheep model as compared with the siloxane control. Contact angle
      measurements and fibrinogen enzyme-linked immunosorbent assay tests were then
      conducted on the POSS-PCU nanocomposite to determine the reason for this
      behavior. The increased fibrinogen adsorption on POSS-PCU, its amphilicity, and
      large contact-angle hysteresis indicated that POSS-PCU inhibits inflammation by
      adsorbing and inactivating fibrinogen on its surface. In complete contrast, the
      control siloxane in the same setting demonstrated very significant inflammation
      and degradation, resulting in capsular formation. Naturally, there was no
      evidence of degradation of the nanocomposite compared with the siloxane control.
      CONCLUSIONS: POSS-PCU nanocomposites have enhanced interfacial biocompatibility
      and better biological stability as compared with conventional silicone
      biomaterials, thus making them safer as tissue implants.

PMID- 17440338
TI  - Use of AlloDerm in primary nipple reconstruction to improve long-term nipple
      projection.
AB  - BACKGROUND: The objective of this study was to demonstrate the use of the
      authors' technique to improve long-term maintenance of nipple projection by using
      AlloDerm (LifeCell Corp., Branchburg, N.J.) as a central core in nipple
      reconstruction. METHODS: The nipple reconstruction technique involved the use of
      a modified star dermal flap pattern measuring 5 cm in length and 1.0 to 1.5 cm in
      width, depending on the amount of desired projection to match the opposite
      nipple. Then, a 1.5 x 4.5-cm piece of AlloDerm was placed into the core of the
      newly reconstructed nipple and sutured closed. After the incisions were closed,
      an ocular eye bubble protector was used to prevent compressive forces on the
      newly reconstructed nipple, and strict postoperative use of this protector was
      maintained for 6 weeks. RESULTS: A total of 30 nipple reconstructions were
      performed [14 transverse rectus abdominis musculocutaneous (TRAM) flaps and 16
      tissue-expanded breast mounds]. Caliper measurements of nipple projection were
      recorded at the time of surgery and at 3, 6, and 12 months postoperatively.
      Twelve-month average maintenance of nipple projection was 56 percent for the TRAM
      flap group and 47 percent for the tissue-expanded group. There were no infections
      or associated complications. CONCLUSIONS: The authors' results demonstrate that
      the use of a modified star dermal flap pattern with the placement of an AlloDerm
      graft core is a safe, easily performed, and reproducible technique for improving
      the long-term maintenance of projection in reconstructed nipples.

PMID- 17440339
TI  - A retrospective analysis of patient satisfaction with immediate postmastectomy
      breast reconstruction: comparison of three common procedures.
AB  - BACKGROUND: The authors aimed to quantify overall patient satisfaction with three
      breast reconstruction techniques and identify factors that have influenced
      satisfaction. METHODS: Two hundred sixty-eight questionnaires were mailed at
      least 6 months after immediate breast reconstruction to consecutive breast
      reconstruction patients over a 3-year period. A second questionnaire was sent out
      9 months later to the tissue expander/implant group of patients. RESULTS: The
      initial questionnaire demonstrated that overall satisfaction was significantly
      greater in the transverse rectus abdominis myocutaneous (TRAM) flap patients as
      compared with the tissue expander/implant patients (p < 0.05). However, the
      number of patients willing to repeat the procedure and recommend their procedure
      to a friend was similar among all three reconstructive techniques. A
      significantly greater number of tissue expander/implant patients as compared with
      TRAM flap patients felt they had not received sufficient information to make an
      educated decision (p < 0.05). This finding correlated with the lower satisfaction
      rate among the tissue expander/implant patients. The second questionnaire sent
      only to the tissue expander/implant patients revealed that the majority felt
      uninformed about the final aesthetic outcome and the frequency and pain
      associated with the expansion process. CONCLUSIONS: All three groups may claim to
      be satisfied with their own personal choices. Many patients will continue to
      choose tissue expander/implant reconstruction in an effort to avoid scars and
      more extensive surgery. Being less satisfied is not wrong or bad, provided it is
      known. Tissue expander/implant patients should be thoroughly informed in the
      preoperative setting about the final aesthetic outcomes and the immediate
      perioperative expansion period, which may involve a considerable amount of
      patient commitment and discomfort in some women.

PMID- 17440341
TI  - Computer-assisted evaluation of nipple-areola complex sensibility in macromastia
      and following superolateral pedicle reduction mammaplasty: a statistical
      analysis.
AB  - BACKGROUND: The authors performed a prospective study quantifying nipple-areola
      complex sensibility by computer-assisted neurosensory testing in breast
      hypertrophy before and after superolateral breast reduction. METHODS: A
      superolateral pedicle breast reduction was performed on 30 macromastia patients.
      The mean age of the patients was 46 years. The cup sizes of the patients were as
      follows: D, 14 patients; E, 12 patients; and EE, four patients. Ptosis was 3
      degrees in 12 and 4 degrees in 18; nipple elevation ranged from 4 to 18 cm;
      glandular resection ranged from 379 to 1850 g. Static and moving one- and two
      point discrimination was tested preoperatively and 6 months postoperatively at
      the nipple-areola complex, evaluating the impact of breast hypertrophy (D versus
      E and EE cups), nipple elevation (<9 cm versus > or =9 cm), and glandular
      resection (<900 g versus > or =900 g). RESULTS: Statistical analyses revealed
      preoperatively significant higher pressure thresholds in the nipple-areola
      complex of larger versus smaller hypertrophies and in the nipple of longer nipple
      areola complex transposition breasts for static and moving one-point
      discrimination. Postoperatively, worsening of sensibility was more significant in
      the nipple-areola complex of smaller versus larger hypertrophies and of shorter
      versus longer nipple-areola complex transposition breasts for moving one-point
      discrimination. CONCLUSIONS: This study confirms that macromastia patients
      present a reduced breast sensibility, which is not necessarily worsened by
      reduction mammaplasty. After reduction mammaplasty with the superolateral pedicle
      technique, nipple-areola complex sensibility might be slightly reduced, which is
      less detectable in large-breast hypertrophy because of lower preoperative levels
      of sensibility and less of a postoperative decrease.

PMID- 17440342
TI  - Contractile properties of single permeabilized muscle fibers from congenital
      cleft palates and normal palates of Spanish goats.
AB  - BACKGROUND: Analysis of the composition of muscle fibers constituent to a cleft
      palate could provide significant insight into the cause of velopharyngeal
      inadequacy. The authors hypothesized that levator veli palatini muscle
      dysfunction inherent to cleft palates could affect the timing and outcome of
      cleft palate repair. METHODS: Single, permeabilized muscle fibers from levator
      veli palatini muscles of three normal (n = 19 fibers) and three chemically
      induced congenital cleft palates (n = 21 fibers) of 14-month-old goats were
      isolated, and contractile properties were evaluated. The maximum isometric force
      and rate constants of tension redevelopment (ktr) were measured, and the specific
      force and normalized power were calculated for each fiber. RESULTS: The ktr
      measures indicate that cleft fibers are predominantly fast-fatigable; normal
      fibers are slow fatigue-resistant: after a 10-minute isometric contraction,
      fibers from cleft palates had a loss of force 16 percent greater than that from
      normal palates (p = 0.0001). The cross-sectional areas of the fibers from cleft
      palates (2750 +/- 209 microm2) were greater (p = 0.05) than those from normal
      palates (2226 +/- 143 microm2). Specific forces did not differ between the two
      groups. Maximum normalized power of fibers from cleft palates (11.05 +/- 1.82
      W/l) was greater (p = 0.0001) than fibers from normal palates (1.60 +/- 0.12
      W/l). CONCLUSIONS: There are clear physiologic differences in single muscle
      fibers from cleft palates and normal palates: cleft palate fibers are
      physiologically fast, have greater fatigability, and have greater power
      production. Detection of functional and/or fiber type differences in muscles of
      cleft palates may provide preoperative identification of a patient's
      susceptibility to velopharyngeal inadequacy and permit early surgical
      intervention to correct this clinical condition.

PMID- 17440343
TI  - Selective percutaneous desiccation of the perforators with radiofrequency for
      strategic transfer of angiosomes in a sequential four-territory cutaneous island
      flap model.
AB  - BACKGROUND: Research in prevention of partial flap necrosis has recently
      concentrated on extending the safe length of a flap by ligating vessels of known
      territories. To advance this approach one step further, the authors decided to
      reveal the least invasive surgical strategy for transfer of angiosomes. METHODS:
      The study was arranged into three experiments. In the first experiment (n = 17
      rabbits), a cutaneous island flap model spanning four adjacent vascular
      territories was developed. In the second experiment (n = 15 rabbits), the flap
      model was used to test the possibility of desiccating those vessels supplying the
      angiosomes to be captured percutaneously with radiofrequency. The delay
      procedures were performed by means of minimal skin incisions, and the flaps were
      elevated after a 2-week delay period. In the third experiment, the effectiveness
      of selective interference of these pedicles was compared to minimize the number
      of target vessels for successful transfer of angiosomes. RESULTS: The mean
      surviving area of the new flap model was 63 +/- 2 percent. The mean surviving
      flap area was 97 +/- 3 percent for the endoscopy equivalent technique and 94 +/-
      4 percent for radiofrequency delay. The results were statistically insignificant
      between these two groups. In experiment 3, comparison of the results yielded a
      statistically insignificant difference for flap survival area among all four of
      the groups. CONCLUSIONS: An alternative flap model is introduced for future
      investigation of the vascular delay process. Percutaneous desiccation of the
      perforators with radiofrequency was found to be a reliable method, and selective
      desiccation of the perforator(s) was as efficient as destruction of all vascular
      sources other than the pedicle.

PMID- 17440344
TI  - Formation of cartilage in vivo with immobilized autologous rabbit auricular
      cultured chondrocytes in collagen matrices.
AB  - BACKGROUND: The availability of generated cartilage de novo is one of the needs
      of reconstructive surgery. In this study, the authors constructed a matrix formed
      by autologous immobilized chondrocytes using collagen gel as a scaffold.
      Furthermore, the ability of these matrices to engraft and generate new cartilage
      was examined. METHODS: Biopsy specimens of elastic cartilage were surgically
      obtained from the ears of eight New Zealand White rabbits. After collagenase II
      digestion of cartilage, chondrocytes were isolated and propagated in culture
      medium. Chondrocytes were immobilized into bovine collagen lattices and
      implanted, replacing pieces of removed native cartilage. Five weeks after
      implantation, the rabbits were killed and the ears were examined macroscopically
      and analyzed by means of histochemical methods. RESULTS: The results show the
      formation of new cartilage from implanted lattices with chondrocytes. Gross
      analysis of the ears shows similarities in appearance, consistency, texture, and
      histology between native and new cartilage. Fluorescence of the nucleus from
      bisbenzimide-labeled chondrocytes was detected in newly formed tissue, pointing
      out its in vitro culture origin. No signs of an inflammatory reaction
      attributable to implants were found in either the control or the chondrocyte
      lattices. CONCLUSION: The authors suggest that this approach is of value for
      future clinical use.

PMID- 17440345
TI  - Fas-mediated apoptotic signal transduction in keloid and hypertrophic scar.
AB  - BACKGROUND: The pathogenesis of keloid and hypertrophic scar is less well
      understood because of the lack of animal models. The cell-surface Fas receptor,
      which is widely distributed in skin components, has been shown to be an important
      factor that induces apoptosis in human dermal fibroblasts. In this report, the
      authors performed a comparative study on apoptotic signal transduction in
      fibroblasts derived from keloids and hypertrophic scars. METHODS: Fibroblasts
      harvested from 10 patients with keloids and hypertrophic scars were used for this
      study. At first, apoptosis induction using Fas antibody and C2-ceramide were
      evaluated using electron microscopy and flow cytometry. Second, the expression of
      the apoptosis-related proteins Fas and Bcl-2 were measured by means of flow
      cytometry. Third, ceramide was measured by quantitative derivatization to
      ceramide-1-phosphate using diacylglycerol kinase and [gamma-32P] ATP. Moreover,
      intercellular Ca2+ was investigated using confocal microscopic analyses. RESULTS:
      In contrast to hypertrophic scar-derived fibroblasts, those derived from keloids
      are significantly resistant to Fas-mediated apoptosis. The intercellular ceramide
      and Ca were not activated. There were no significant differences in the level of
      expression of Bcl-2 between the two groups, but Fas expression was higher in
      keloid than in hypertrophic scar. Fibroblasts from the two groups were
      susceptible to ceramide-induced apoptosis. CONCLUSIONS: Blocking of the Fas
      mediated apoptotic pathway in keloids occurs upstream of the second messenger.
      The abnormal Fas-induced apoptosis in keloids may account for the imbalance of
      proliferation and apoptosis. Enhancement of Fas sensitivity could be a promising
      therapeutic target.

PMID- 17440346
TI  - Scarring occurs at a critical depth of skin injury: precise measurement in a
      graduated dermal scratch in human volunteers.
AB  - BACKGROUND: The association between scarring and the depth of dermal injury or
      burn is clinically recognized but not quantified. The authors tested the
      hypothesis that there is a critical depth beyond which a fibrous scar develops.
      METHODS: A novel jig produced a wound that was deep dermal at one end and
      superficial dermal at the other. Pilot studies in cadaveric and ex vivo breast
      skin confirmed the depth of injury. Healthy volunteers had a standardized dermal
      wound made on the lateral aspect of the hip. Digital photography recorded the
      surface appearance of wound healing and scar development. High-frequency
      ultrasound demonstrated the depth of the healing wound and subsequent scar in
      vivo. RESULTS: One hundred thirteen human subjects participated in the clinical
      study. Mean length of follow up was 28.6 +/- 13.2 weeks. The deep dermal end of
      the wound healed with a visible scar and the superficial end had no visible
      residual mark after week 18. The initial length of injury was 51.3 +/- 0.6 mm,
      which reduced to a scar of 34.9 +/- 1.0 mm at 36 weeks (corresponding areas were
      196.6 +/- 7.5 mm and 92.7 +/- 9.4 mm). High-frequency ultrasound analysis showed
      a gradual reduction in scar thickness at the deep end and no detectable scar at
      the shallow end. The transition point between scar and no scar marked the
      threshold depth for scarring. This was calculated as 0.56 +/- 0.03 mm, or 33.1
      percent of normal hip skin thickness. CONCLUSIONS: The dermal scratch provides a
      well-tolerated, standardized, and reproducible wound model for investigating the
      healing response to dermal injury of different depths. There is a threshold depth
      of dermal injury at which scarring develops.

PMID- 17440348
TI  - Vascular delay revisited.
AB  - The technique of vascular delay has been used by plastic surgeons for nearly 500
      years and has proven useful for reliably transferring tissue and allowing for a
      greater volume of tissue to be reliably harvested. Delay procedures are an
      essential plastic surgical tool for a variety of aesthetic and reconstructive
      procedures. Despite the widespread use of vascular delay procedures, the
      mechanism by which this phenomenon occurs remains unclear. A number of groups
      have exhaustively examined microvascular changes that occur during vascular
      delay. Theories have been proposed ranging from the dilation of choke vessels to
      changes in metabolism and new blood vessel formation. Inherent in these theories
      is the concept that ischemia is able to act as the primary stimulus for vascular
      changes. The purpose of this review is to revisit the theories proposed to
      underlie the delay phenomenon in light of recent advances in vascular biology. In
      particular, the participation of bone marrow-derived endothelial progenitor cells
      in the delay phenomenon is explored. Greater understanding of the role these
      cells play in new blood vessel formation will be of considerable clinical benefit
      to high-risk patients in future applications of delay procedures.

PMID- 17440349
TI  - Blood gas analysis of the jejunum in the supercharge technique: to what degree
      does circulation improve?
AB  - BACKGROUND: The supercharge technique has become widely prevalent in the field of
      esophageal reconstruction. Despite the logical advantages with this technique,
      the actual degree of its effect on the blood circulation is not clear. There may
      be cases in which the supercharge technique is not necessary for survival of the
      jejunum. To decide whether or not the supercharge technique is indicated, it is
      crucial to know how effective it is in improving blood flow to the jejunum.
      METHODS: The effect of the additional vessel anastomosis in the pedicled jejunal
      transfer was evaluated by blood gas analysis of the venous blood in the
      mesenteric vein. In 27 patients undergoing pedicled jejunal transfer with
      additional vessel anastomosis using the internal mammary vessels for
      reconstruction of the thoracic esophagus, intraoperative blood sampling was
      performed three times: before anastomosis, after venous anastomosis, and after
      venous and arterial anastomosis. RESULTS: The venous partial pressure of oxygen
      showed little increase after the venous anastomosis (mean, 115.7 percent; p =
      0.0022). In contrast, venous partial pressure of oxygen increased markedly after
      the arterial and venous anastomosis in most of the patients (mean, 177.8 percent;
      p < 0.0001). Similarly, venous partial pressure of carbon dioxide, after both
      anastomoses, decreased to a lower level than before the additional anastomosis in
      most patients (mean, 93.1 percent; p = 0.035). CONCLUSION: The authors conclude
      that the additional anastomosis of both the artery and the vein is recommended if
      it is possible.

PMID- 17440350
TI  - APACHE II scoring for the prediction of immediate surgical complications in head
      and neck cancer patients.
AB  - BACKGROUND: Aggressive surgical treatment of oral and oropharyngeal cancers may
      be compromised by significant surgical complications. Early identification of
      patients at risk for postoperative complications may assist in clinical decision
      making. The objective of this study was to assess the value of the Acute
      Physiology and Chronic Health Evaluation (APACHE II) score in predicting early
      postoperative surgical complications. METHODS: There were 510 cases of free
      tissue transfer surgery identified on the Liverpool Oncology Head and Neck
      Database for 1995 to 2002. APACHE II data were collected independently from
      critical care records and by case note retrieval. The authors' main a priori
      outcomes were total flap failure and any immediate complication requiring further
      surgery (including any from hemorrhage, hematoma, partial flap failure, airways,
      and anastomosis exploration). RESULTS: Overall total flap loss and immediate
      complication rates were 6.2 percent (30 of 485) and 13.6 percent (66 of 485),
      respectively. APACHE II data were known for 399 operations (82 percent) and, of
      these, 90 percent (360 of 399) were managed postoperatively in the critical care
      unit. There were clear correlations between APACHE II scores with total flap loss
      and with other immediate complications. CONCLUSIONS: The APACHE II score is
      associated with immediate postoperative surgical complications involving flap
      compromise and thus may be a useful tool in postoperative decision-making.

PMID- 17440351
TI  - Partial necrosis of expanding postauricular flaps during auricle reconstruction:
      risk factors and effective management.
AB  - BACKGROUND: Tissue expansion has gradually become accepted as a useful adjunct to
      auricular reconstruction. Necrosis of postauricular flaps during the expansion
      phase may hinder auricular reconstruction. This study was designed to investigate
      the risk factors for partial necrosis of expanding postauricular flaps during
      reconstruction of the auricle and to provide effective management strategies.
      METHODS: Data were gathered retrospectively for cases of partial necrosis of
      expanding postauricular flaps from the overall group of patients undergoing
      auricular reconstruction after preliminary tissue expansion at a treatment center
      from January of 2002 to January of 2005. Demographic data, ulcer occurrence,
      treatment procedure, and results were analyzed statistically. RESULTS: The
      authors observed that 2.5 percent of congenital microtia cases and 13.8 percent
      of acquired auricular defect cases suffered from partial necrosis of expanding
      postauricular flaps. Necrosis in more cases occurred during static expansion and
      was located on the inferior part of the expanded flap. Treatment included the
      following: (1) auricular reconstruction with autologous costal cartilage or a
      porous polyethylene framework for a limited term; (2) continuing static
      expansion, with the postauricular flap extended and fixed in place after expander
      removal; and (3) removal of the expander and reinsertion of a similar expander
      more than 6 months after the wound had healed. Each method was applied to
      different types of cases. Most cases obtained a satisfactory contour and profile
      of the reconstructed auricle. CONCLUSIONS: Some individual and iatrogenic factors
      are involved in partial necrosis of expanding postauricular flaps, which can be
      prevented and minimized. An optimal method can be chosen to treat every case of
      partial necrosis of the expanding postauricular flap.

PMID- 17440352
TI  - Reconstruction of lower half defects of the nose with the lateral nasal artery
      pedicle nasolabial island flap.
AB  - BACKGROUND: The superiorly based nasolabial flap is a well-known procedure.
      However, random pattern or subcutaneous pedicle flaps are insufficient for
      reconstruction of large defects. Artery pedicle flaps have a satisfactory blood
      supply, and for that reason, the required tissue can be raised for reconstruction
      of large defects of the nose. METHODS: Twelve cases were operated on with this
      technique. Reconstruction was performed with a lateral nasal artery pedicle
      island flap. The mean age of the patients was 68.4 years. Three patients required
      cartilage grafts for alar rim support. The cartilage grafts were harvested from
      the auricular conchal bowl. The follow-up period ranged from 15 to 33 months.
      RESULTS: There was no partial or total loss of the flap. There was no distortion
      on the face caused by smiling and pursing of the lips observed. Donor and
      reconstructed areas have an excellent appearance in all cases. The aesthetic
      results were satisfying for all patients as well. CONCLUSIONS: The authors' flap
      can be used for reconstructing large defects of the lower half of the nose, and
      reconstruction with a single stage yields a fast and satisfactory result. The
      authors advocate that the lateral nasal artery pedicle nasolabial island flap is
      an excellent choice for reconstruction of large defects in the lower half of the
      nose.

PMID- 17440353
TI  - The role of apoptosis in traumatic versus nontraumatic nasal septal cartilage.
AB  - BACKGROUND: Nasal surgery is occasionally performed to correct traumatic nasal
      deformity. Septal cartilage is the main tissue to be corrected and is a graft
      source when needed. A risk in engrafting with cartilage is the possibility of
      resorption as a result of either necrosis or apoptosis. The authors evaluated the
      rate of apoptosis in deviated and straight cartilage to investigate the cause of
      resorption of cartilage tissue. METHODS: Twenty-five patients with traumatic
      nasal septum deviation (group I) and 13 patients with nontraumatic nasal septum
      deviation (group II) were prospectively enrolled. After correction of the
      deviation, two small samples of cartilage were harvested, one from the deviated
      site (group Ia or IIa) and the other from the straight site (group Ib or IIb),
      immediately frozen at -70 masculineC, and evaluated for apoptosis using DNA
      agarose gel electrophoresis. RESULTS: Apoptosis was detected in 14 (56 percent)
      of the deviated and two (8 percent) of the straight cartilage samples in
      traumatic patients, whereas it was detected in only one deviated sample (7.7
      percent) and none of the straight samples in nontraumatic patients. The apoptosis
      rates in group Ia were statistically significant when compared with groups Ib (p
      = 0.0007) and IIa (p = 0.0007). CONCLUSIONS: The present study demonstrates that
      apoptosis occurs in traumatized nasal septal cartilage. Apoptosis might be the
      factor leading to cartilage resorption, weakness, and warping when used as a
      graft. Thus, cartilage grafting materials should be taken from the nontraumatized
      portion of the septum and should not be traumatized either during harvesting or
      before placement.

PMID- 17440355
TI  - Microscopic margins and results of surgery for dermatofibrosarcoma protuberans.
AB  - BACKGROUND: Dermatofibrosarcoma protuberans is a rare low-grade sarcoma of the
      skin with a tendency to recur locally after inadequate excision. Treatment has
      traditionally been wide excision with a 2- to 3-cm gross margin. Because of the
      variable results presented in mainly retrospective reports, it has been queried
      whether local control can be as good with conventional surgery as with
      micrographic surgery. METHODS: Forty patients with dermatofibrosarcoma
      protuberans treated by surgical excision were operated on at our center from 1987
      to 2001. Data were recorded prospectively. Twenty-seven patients presented with a
      primary tumor and 13 with a locally recurrent tumor primarily operated on
      elsewhere. Gross and histologic margins were studied in detail. RESULTS: At a
      mean follow-up of 40 months, there were no recurrences. Thirty-four patients
      required single, five patients two, and one patient three operations before the
      margins were adequate (mean, 1.2 stages per patient). Twenty-three patients (58
      percent) needed reconstructions. Tumor-free margins were obtained in 39 patients.
      The average thickness of surgical gross margins was 3.1 cm; histologically
      defined margins averaged 1.6 cm. CONCLUSIONS: Good local control can be achieved
      with wide surgery. Histologic tumor-free margins differ greatly from gross
      margins and are difficult to assess clinically and macroscopically. Careful
      postoperative histologic examination with margins measured in millimeters should
      be carried out to define the adequacy of excision in all directions. On average,
      a 1.6-cm histologic margin was adequate for complete local control. Most patients
      can be operated on in one stage. Reconstructions are often needed.

PMID- 17440356
TI  - A new technique of vaginal reconstruction with the deep inferior epigastric
      perforator flap: a preliminary report.
AB  - BACKGROUND: Vaginal reconstruction after tumor resection or in congenital vaginal
      agenesis remains a challenging area in surgery, with many techniques previously
      described underlining the continued search for an ideal method. In this
      preliminary report, a series of patients are presented who underwent vaginal
      reconstruction using a deep inferior epigastric artery perforator (DIEP) flap.
      METHODS: Between May of 2004 and February of 2005, five patients underwent
      vaginal reconstruction using the pedicled DIEP flap. Four patients had congenital
      vaginal agenesis and one had a complete vaginal resection because of a tumor.
      RESULTS: The flaps ranged in size from 9 x 10 cm to 11 x 12 cm. All flaps
      survived, although one patient developed a posterior space hematoma that required
      draining. Of the five patients, two were sexually active and enjoyed satisfactory
      penetrative intercourse after reconstruction. CONCLUSIONS: This series
      demonstrates that a new vagina can be created from the pedicled DIEP flap and
      that the reconstruction is reliable, with low donor-site morbidity. The major
      disadvantage of this technique is the conspicuous abdominal scar.

PMID- 17440358
TI  - Components separation combined with abdominal wall plication for repair of large
      abdominal wall hernias following bariatric surgery.
AB  - BACKGROUND: Abdominal wall hernias frequently occur after open bariatric surgical
      procedures. Standard repair with synthetic mesh may be suboptimal, with a
      recurrence rate as high as 50 percent. Patients often seek hernia repair in
      conjunction with abdominal body contouring procedures following substantial
      weight loss. METHODS: In 66 consecutive patients undergoing abdominal surgery
      after open bariatric surgery, abdominal wall hernias of some size were found in
      50 patients. In 65 of these patients, panniculectomy was performed
      simultaneously. The majority of these hernias could be closed primarily in
      conjunction with abdominal wall plication [38 of 50 (76 percent)]. In 12 patients
      (24 percent of hernias), the defects were too large (median, 10.8 cm) or located
      too close to the xiphoid to permit primary closure without undue tension.
      RESULTS: Using a components separation technique, primary fascial closure was
      achieved in all 12 patients. The technique was modified to include abdominal wall
      plication above and below the repaired hernia defect and the use of an absorbable
      mesh onlay. Although these patients had a high rate (50 percent) of minor or
      major superficial wound complications, all wounds closed subsequently without
      additional operative procedures. Despite the high-risk nature of this group,
      ventral hernia recurred in only one of 12 patients (8.3 percent) after a median
      follow-up of 16 months. The single recurrence occurred in one of the two patients
      with the largest diameter (15 cm) hernias in the series. CONCLUSIONS: The
      components separation technique combined with abdominal wall plication was
      assessed as the preferred technique for the repair of large hernias not amenable
      to primary repair in the massive weight loss patient following open bariatric
      procedures. Because this technique avoids placement of permanent mesh, it is
      particularly advantageous in the post-bariatric surgery patient at high risk for
      wound dehiscence and infection.

PMID- 17440359
TI  - Pacman flap method.
AB  - BACKGROUND: The V-Y flap is a well-known method for closure of round skin
      defects. However, with conventional V-Y flaps, it is sometimes difficult to
      advance the flap sufficiently, especially where there is a lack of subcutaneous
      tissue. Thus, the authors have devised a new technique named after a famous
      Japanese video game. METHOD: The flap design is almost the same as a conventional
      V-Y flap. Instead of cutting off the two triangular parts of the V flap, those
      two parts are rotated and advanced to meet at the center of the defect. RESULTS:
      The authors have operated on 18 patients with this method, and in all the cases,
      the flap survived completely. No secondary surgery was required to correct dog
      ear deformity. CONCLUSIONS: This method is easy and can be applied in many
      situations. The authors conclude that this can be the first choice for closing
      circular skin defects.

PMID- 17440360
TI  - Mortality in patients with necrotizing fasciitis.
AB  - BACKGROUND: The prognostic factors that determine outcome in patients with
      necrotizing fasciitis remain poorly understood. The aim of this study was to
      analyze the variables that affect the mortality and morbidity of patients with
      necrotizing fasciitis and to create a simple method for estimating the
      probability of mortality. METHODS: The authors undertook a retrospective review
      of all patients with necrotizing fasciitis treated in three tertiary care
      hospitals in Ontario, Canada, between January of 1994 and June of 2001.
      Demographic, comorbid illness, and disease-specific data were collated and
      analyzed for associations with outcome. Using logistic regression analysis,
      probability estimates for the prediction of mortality were developed, based on
      three contributing independent factors. RESULTS: Ninety-nine patients satisfied
      the inclusion criteria. Overall mortality was 20 percent. Sixteen patients
      suffered from amputation or organ loss. The most common comorbidities were
      diabetes (30 percent), immunocompromised status (17 percent), and chickenpox (11
      percent). Advanced age (odds ratio, 1.04; 95 percent confidence interval, 1.01 to
      1.08; p = 0.012), streptococcal toxic shock syndrome (odds ratio, 10.54; 95
      percent confidence interval, 2.80 to 39.44; p < 0.001), and immunocompromised
      status (odds ratio, 3.97; 95 percent confidence interval, 1.04 to 15.19; p =
      0.044) were independent predictors of mortality and were used to design a formula
      for the probability of mortality. CONCLUSIONS: Age, streptococcal toxic shock
      syndrome, and immune status are significant determinants of mortality and can
      predict the probability of death from necrotizing fasciitis soon after admission.
      This objective information can guide clinicians in communication with patients
      and in making clinical decisions.

PMID- 17440361
TI  - Distally based greater saphenous venoadipofascial-sartorius muscle combined flap
      with venous anastomosis.

PMID- 17440362
TI  - The lymphatic territories of the upper limb: anatomical study and clinical
      implications.
AB  - BACKGROUND: Current understanding of the pattern of lymph channels is largely
      dependent on the anatomical studies of Sappey performed in the nineteenth
      century, when mercury was injected into human cadavers and the lymphatics were
      dissected. These studies have not been repeated because the use of mercury is now
      prohibited as a result of its toxicity. The aim of this study was to reappraise
      the gross lymphatic anatomy and lymph node connections using a radiologic
      technique. A period of 3 years was required for development of a new method.
      METHODS: The definitive technique used hydrogen peroxide to identify lymphatic
      vessels and to inflate them. The individual channels were injected with a
      radiopaque lead oxide mixture and recorded on x-ray film. Each channel was
      dissected meticulously under the surgical microscope and its course examined in
      relation to the regional lymph nodes. This method was then applied to 14 human
      cadaver upper limbs obtained from 10 different cadavers. RESULTS: The authors
      found that the superficial lymphatic vessels course within the subcutaneous fat
      in close proximity to the main subcutaneous veins. Communication between the
      superficial and the deep lymphatic systems was not identified in these studies.
      CONCLUSIONS: Most lymph vessels were seen to flow into one main (sentry) lymph
      node in the axillary region; however, some of the lymph vessels ran along the
      posterior forearm, bypassing the "sentry" node to reach other smaller nodes.

PMID- 17440363
TI  - A retrospective analysis of 154 arterialized venous flaps for hand
      reconstruction: an 11-year experience.
AB  - BACKGROUND: The purpose of this study was to present the authors' 11-year
      clinical experience involving 154 cases of arterialized venous flaps for hand
      reconstruction. METHODS: The authors classified the venous flaps based on their
      size and composition. According to their size, flaps smaller than 10 cm were
      classified as small (n = 48), flaps larger than 25 cm were classified as large (n
      = 42), and those in between were classified as medium (n = 64). Classified
      according to their composition, there were 88 cases (57.1 percent) of venous skin
      flaps, 28 cases (18.2 percent) of innervated venous flaps, 15 cases (9.7 percent)
      of tendocutaneous venous flaps, and 17 cases (11 percent) of conduit venous flaps
      to repair arterial defects. There were six cases (3.9 percent) of composite
      venous flaps. RESULTS: The success rate of the flap transfer was 98.1 percent.
      The incidence of partial flap necrosis was 5.2 percent. The mean number of
      included veins was 2.17 for a small flap, 2.60 for a medium-sized flap, and 4.07
      for a large flap (p < 0.01). The mean area of flap necrosis was 45.0 percent,
      31.67 percent, and 18.75 percent for small, medium, and large flaps, respectively
      (p = 0.807). In eight cases of innervated venous flaps, the average static two
      point discrimination was 10 mm (range, 8 to 15 mm). In 12 cases of tendocutaneous
      venous flaps, active range of motion at the proximal interphalangeal, distal
      interphalangeal, and metacarpophalangeal joints was 60, 20, and 75 degrees,
      respectively. CONCLUSIONS: The authors conclude that the arterialized venous flap
      is a valuable and effective tool for reconstructing complex hand injuries and may
      have a more comprehensive set of indications.

PMID- 17440364
TI  - Comparison of biodegradable conduits within aged rat sciatic nerve defects.
AB  - BACKGROUND: Considering that little is known about the peripheral nerve
      regenerative capacity of elderly patients, the authors studied nerve regenerative
      capacity in aged rats and compared the effect of three synthetic nerve guides
      with different material characteristics and porosity. The authors hypothesized
      that the use of a biodegradable composite nerve guide (CultiGuides) would promote
      nerve regeneration and functional recovery in a manner similar to treatment with
      autografts or U.S. Food and Drug Administration-approved polyglycolic acid
      Neurotubes in an aged rat sciatic nerve defect model. METHODS: Aged Sprague
      Dawley rats (11 months old) underwent a 1-cm sciatic nerve resection in the right
      leg [group 1, control (contralateral leg samples), n = 10; group 2, negative
      (nerve gap defect), n = 6; group 3, autograft, n = 10; group 4, polycaprolactone,
      n = 10; group 5, CultiGuides, n = 10; and group 6, Neurotube, n = 10]. RESULTS:
      After 12 weeks, the negative group did not demonstrate any nerve regeneration. In
      the regenerated and distal nerve, all treated groups had increased myelinated
      areas compared with the negative control. In the regenerated nerve, there was a
      significant increase in myelination in the Neurotube group compared with the
      polycaprolactone group (p < 0.001). However, in the distal nerve, there were no
      differences among the treatment groups. Walking track analyses and gastrocnemius
      muscle weight ratios were not different among treatment groups 3 through 6.
      CONCLUSIONS: The results showed differences in myelination; Neurotubes promoted
      the highest degree of myelination (p < 0.001) as compared with all groups. The
      authors found no improvement in function of the repaired nerve as measured by
      percentage of autotomy, the sciatic function index, and gastrocnemius muscle
      weight. No group was able to recover function in this aged model.

PMID- 17440365
TI  - Soft-tissue coverage of the elbow: an outcome analysis and reconstructive
      algorithm.
AB  - BACKGROUND: Soft-tissue defects surrounding the elbow can be a challenging
      problem for the reconstructive surgeon. Multiple reconstructive options are
      available, but there are few published outcome studies. The authors performed an
      outcome analysis of soft-tissue coverage for elbow defects to determine the
      benefits and limitations of various reconstructive options in this problematic
      area. METHODS: A retrospective review was performed of all elbow defects
      requiring flap coverage from 1988 to 2005. Patient demographics, defect
      characteristics, type of flaps used, complications, and long-term outcomes were
      analyzed. The t test was used for statistical comparison. RESULTS: A total of 99
      flaps were performed in 96 patients. Forty-seven percent of the defects were
      secondary to trauma. Sixty-six percent of the flaps used were pedicled flaps and
      19 percent were free flaps. The most common pedicled flap used was the radial
      forearm flap, whereas the most commonly used free flap was the latissimus dorsi
      muscle flap. Reconstructive failures occurred in 10 percent of patients; these 10
      patients required a second flap for limb salvage. The pedicled latissimus dorsi
      muscle flap had the highest complication rate (57 percent), with distal necrosis
      being the most frequent complication. The pedicled latissimus dorsi flap was
      associated with a higher complication rate when compared with the radial forearm
      flap (p = 0.01). CONCLUSIONS: The pedicled latissimus was associated with a high
      rate of distal necrosis when it was used to cover defects distal to the
      olecranon. The authors recommend the use of the radial forearm flap or a free
      flap for soft-tissue coverage of defects lying over the proximal ulna.

PMID- 17440366
TI  - Does palatal muscle reconstruction affect the functional outcome of cleft palate
      surgery?
AB  - BACKGROUND: This study was designed to compare two-layer palatoplasty (Wardill
      Kilner V-Y pushback technique) without intravelar veloplasty versus three-layer
      palatoplasty (Kriens technique) with intravelar veloplasty with regard to
      postoperative functional outcome of eustachian tube and velopharyngeal
      competence. METHODS: A prospective cohort study was conducted enrolling 70
      patients with nonsyndromic cleft palate (except submucous type of cleft) over a
      period of 2 years. They were divided into two main groups according to the type
      of cleft palate: group A (Veau class II) included 32 patients and group B (Veau
      class I) included 38 patients. In each group, Wardill-Kilner palatoplasty (two
      layer repair without intravelar veloplasty) versus Kriens palatoplasty (three
      layer repair with intravelar veloplasty) was randomly selected for patients.
      RESULTS: For the three-layer palatoplasty in both groups, there was a greater
      tendency for resolution of secretory otitis media in the early postoperative
      period, less time required for extrusion of the grommet tube, and a lower
      incidence of recurrent secretory otitis media. The incidence of postoperative
      velopharyngeal incompetence was greater with two-layer palatoplasty group. The
      incidence of palatal fistula was greater with three-layer palatoplasty.
      CONCLUSIONS: Palatal muscle reconstruction in cleft palate patients confers
      better functional results regarding velopharyngeal competence and eustachian tube
      function. Although the overall incidence of postoperative palatal fistula is
      within the accepted range, the incidence of fistula is higher in the palatal
      muscle reconstruction subgroup. Future studies are required that include a larger
      number of patients.

PMID- 17440367
TI  - Nonsynostotic occipital plagiocephaly: factors impacting onset, treatment, and
      outcomes.
AB  - BACKGROUND: Nonsynostotic occipital plagiocephaly remains a diagnosis of concern
      in infancy. This study evaluates factors affecting the onset, treatment, and
      outcomes of nonsynostotic occipital plagiocephaly. METHODS: A retrospective chart
      review and telephone survey were performed. A posterior occipital deformation
      severity score was used. Factors such as demographics, behavioral and helmet
      therapy, feeding patterns, torticollis, multiple gestation pregnancies,
      prematurity, and congenital nonsynostotic occipital plagiocephaly were evaluated.
      RESULTS: One hundred five infants were identified. Of these, 95 percent were
      Caucasian, 93 percent were from two-parent households, and 70 percent were from
      households earning more than $50,000. Repositioning was attempted in 95 percent,
      and 45 percent progressed to helmet therapy. When comparing change in posterior
      occipital deformation severity score with helmet therapy to repositioning, a
      difference was found (p < 0.05). Forty-nine percent of patients were breast-fed,
      and when compared with the general population, a difference was found (p < 0.05).
      Twenty percent of infants had torticollis, and when compared with population
      norms, a difference was found (p < 0.05). Twelve percent of patients were twins,
      and when compared with population norms, more twinning occurred (p < 0.05).
      Congenital nonsynostotic occipital plagiocephaly was found in 10 percent of
      patients and did not result in an increased risk of progression to helmet
      therapy. CONCLUSIONS: This study demonstrates trends that may predict additional
      risks for developing nonsynostotic occipital plagiocephaly, including
      torticollis, plural births, and increased socioeconomic affluence. In addition,
      the nonsynostotic occipital plagiocephaly cohort was breast-fed less than the
      general population, demonstrating that breast-feeding may be preventative, as
      breast-fed infants are repositioned more frequently and sleep for shorter
      periods. As in other studies, cranial molding helmet therapy was more effective
      in correcting nonsynostotic occipital plagiocephaly than repositioning alone.

PMID- 17440368
TI  - Neurodevelopment of infants with single-suture craniosynostosis: presurgery
      comparisons with case-matched controls.
AB  - BACKGROUND: The hypothesized association between single-suture craniosynostosis
      and neurodevelopment remains unclear, given the methodologic limitations of
      previous studies, most notably the absence of control groups. METHODS:
      Standardized measures were used to assess the neurodevelopment of 125 matched
      case-control pairs shortly after cases were first diagnosed with isolated fusions
      of the sagittal, metopic, lambdoid, or right or left coronal sutures.
      Participants varied in age from 2 to 24 months. RESULTS: Cases had significantly
      lower mean standardized scores than controls on measures of cognitive ability and
      motor functioning (p < 0.02). These differences were unaffected by the location
      of synostosis, age of diagnosis, infant sex, and maternal IQ. Measures of early
      language functions revealed no group differences. CONCLUSIONS: Before
      cranioplasty, single-suture craniosynostosis is associated with modest but
      reliable neurodevelopmental delays that cannot be attributed to maternal
      intelligence and family sociodemographic variables. Follow-up of this sample will
      determine the predictive significance of these delays. In the meantime, routine
      neurodevelopmental screening of infants with isolated craniosynostosis is
      recommended.

PMID- 17440369
TI  - Anterior fontanelle morphology in unilateral coronal synostosis: a clear clinical
      (nonradiographic) sign for the diagnosis of frontal plagiocephaly.
AB  - BACKGROUND: A review of patients with unilateral coronal synostosis treated at
      the Royal Children's Hospital was performed to explore the hypothesis that the
      clinically palpated shape of the anterior fontanelle in nonsyndromic unilateral
      coronal synostosis is triangular rather than the normal diamond shape. METHODS:
      Three-dimensional computed tomographic scans were reviewed to assess the
      morphology of the anterior fontanelle. It is to be noted that these methods are
      purely for the purposes of describing the sign, and a three-dimensional computed
      tomographic scan is not required to elicit this clinical sign. RESULTS: Twenty
      eight patient records were identified, of which 18 had had three-dimensional
      computed tomographic scans. In eight of these, the anterior fontanelle was closed
      at the time of computed tomographic scanning, and in 10 it was open. Of the open
      fontanelles, all were triangular, supporting the hypothesis. CONCLUSIONS: The
      shape of the fontanelle is an additional useful clinical sign with which to
      discriminate between synostotic plagiocephaly (triangular fontanelle) and
      deformational plagiocephaly (diamond-shaped fontanelle), along with those
      previously described by Mulliken and Huang. An algorithm is presented using these
      clinical indicators to both guide and minimize the use of radiology
      investigations.

PMID- 17440370
TI  - Follicular anatomy of the anterior temporal hairline and implications for
      rhytidectomy.
AB  - BACKGROUND: Incisions made perpendicular to the hair follicles during anterior
      frontal hairline brow lifts or forehead shortening procedures help produce an
      inconspicuous forehead scar. The success of this "hidden" incision relies on the
      anteriorly directed frontal hairline follicles and their growth vector. The
      authors hypothesized that a similar incision could be made perpendicular to the
      hair follicles in the temple region during rhytidectomy. A well-designed anterior
      hairline beveled incision over the temple would allow for improved leverage
      during soft-tissue repositioning and a concealed hairline incision in the temple
      region. METHODS: Anterior temporal hairline strips 4 cm in length at the level of
      the lateral canthus were excised from 16 fresh cadavers. Hairline follicles (n =
      227) were assessed for direction and angle of growth after appropriate tissue
      preparation and staining (hematoxylin and eosin). The hair follicle angle was
      analyzed microscopically as it approached the epidermis. RESULTS: The anterior
      temporal hairline follicles were oriented at a mean angle with the epidermis of
      16 +/- 3 degrees anteriorly and inferiorly. CONCLUSIONS: The anterior temporal
      hairline follicles of the scalp are oriented anteriorly and inferiorly with the
      epidermis, providing the surgical rational for using a beveled hairline incision
      angled 30 to 45 degrees to the external skin surface to undercut the distal flap.
      This incision is perpendicular to and transects the temporal hair follicles
      during rhytidectomy, permitting hair growth through and anterior to the scar.
      This modified anterior temporal hairline incision reduces visibility of the scar
      at the hairline for patients in whom scar show and hairstyle versatility are
      important concerns.

PMID- 17440372
TI  - Using the autospreader flap in primary rhinoplasty.
AB  - BACKGROUND: When performing dorsal reduction in primary rhinoplasty, one must pay
      close attention to the height of the upper lateral cartilages. They are in part
      responsible for the dorsal aesthetic lines and often require a lower profile.
      METHODS: The technique the authors describe uses the transverse portion of the
      upper lateral cartilages rotated medially to function as a local spreader flap
      while reducing the profile of the dorsum and preserving the aesthetic lines. This
      is a surgical technique that adjusts the height of the upper lateral cartilages
      in a precise and safe manner while preserving the function of the internal valve.
      RESULTS: The authors present two patients seen at 1 and 3 years after undergoing
      the autospreader flap technique. In the experience of the senior author (H.S.B.)
      with this procedure over the past decade, preoperative surgical goals were
      achieved reliably. CONCLUSIONS: The authors review the anatomical indications in
      which they found this technique to be simple, reproducible, and effective in
      shaping the dorsal midvault while preserving the function of the internal valve.
      Autospreader flap rotation should be considered when dorsal reduction is
      required.

PMID- 17440373
TI  - The spreader flap in primary rhinoplasty.
AB  - BACKGROUND: In a primary rhinoplasty that requires a humpectomy, the dorsal
      aspect of the upper lateral cartilages is commonly discarded. Many of these
      patients need spreader grafts to reconstruct the middle third of the nose.
      However, it is possible to reconstruct the upper lateral cartilages into
      "spreader flaps" that act much like spreader grafts. METHODS: A tunnel is created
      on the underside of the upper lateral cartilage, which is released from the
      cartilaginous septum and also from its attachment to the nasal bone (medially).
      It is then rolled on itself to make a spreader flap, which is secured with
      sutures. Scoring along the dorsal edge of the upper lateral cartilage may be
      necessary. The flap is then secured to the dorsal edge of the reduced dorsal
      septum. RESULTS: In 21 patients who underwent an open approach (and four patients
      who underwent the closed approach), the spreader flap almost always reconstructed
      the middle third of the nose. It was easy to execute in the open approach but
      difficult in the closed approach. At surgery, two patients undergoing the open
      approach and one patient undergoing the closed approach needed spreader grafts
      because the flaps were too narrow. Postoperatively, only one patient (operated on
      by the open approach) exhibited inadequate nasal width. CONCLUSIONS: Spreader
      grafts are the standard for reconstructing the middle third of the nose. However,
      the spreader flap avoids harvesting and carving cartilage for those grafts. In
      the open approach, the technique is easy to execute. Conclusions could not be
      drawn regarding the long-term success with the closed approach.

PMID- 17440374
TI  - Modified vertical abdominoplasty in the massive weight loss patient.
AB  - BACKGROUND: Patients with massive weight loss following bariatric surgery are now
      presenting in large numbers for body contouring. To achieve optimum cosmetic
      results in these patients, a comprehensive circumferential approach is usually
      required that includes the lateral thighs and buttocks. For a number of reasons,
      many patients are not candidates for these comprehensive procedures. Some
      patients view the circumferential procedures as too extensive or aggressive.
      Others have large hernias or other medical conditions that necessitate a more
      limited approach. Still others do not have sufficient resources to treat multiple
      areas. METHODS: A 2-year review of patients presenting with a chief complaint of
      anterior lower abdominal tissue excess as a consequence of massive weight loss
      following bariatric procedures was conducted. In 64 cases, patients opted for
      anterior-only treatment of the lower trunk. RESULTS: Average operative time in
      patients undergoing modified abdominoplasty alone was 2.5 hours. The mean mass of
      the excised panniculectomy specimens was 3.8 kg (range, 1.1 to 10.0 kg). The most
      common complication was wound dehiscence at the T-junction (27 percent), which
      was treated successfully with local wound care in all cases and did not require
      reoperation to achieve wound closure. There were no known thromboembolic events.
      CONCLUSIONS: Not all massive weight loss patients are suitable candidates for
      comprehensive circumferential body contouring procedures, and many patients
      desire a limited anterior approach to the frontal abdomen. The modified vertical
      abdominoplasty should be considered as an option in these patients.

PMID- 17440376
TI  - Body dysmorphic disorder: diagnosis and approach.
AB  - Body dysmorphic disorder is a psychiatric disease that can be frequently
      encountered in an aesthetic practice. Body dysmorphic disorder is characterized
      by a preoccupation with a minimal or nonexistent appearance defect and causes
      significant distress and interferes with the social life of the patient. The
      perceived physical anomaly may involve the shape and size of the whole body or
      may be centered around single units. Body dysmorphic disorder patients are known
      to request multiple aesthetic procedures that leave them unsatisfied. Only a
      timely diagnosis will enable the surgeon and staff to adequately address the
      patient's needs. Body dysmorphic disorder patients cannot be cured with surgery.
      Diagnostic techniques such as patient interview and observation are presented in
      this article. With this, the plastic surgeon should be able to diagnose body
      dysmorphic disorder preoperatively. Using the presented algorithm to approach
      body dysmorphic disorder patients will avoid disappointment for patients and
      surgeons alike.

PMID- 17440377
TI  - Continuing medical education in emergency plastic surgery for referring
      physicians: a prospective assessment of educational needs.
AB  - BACKGROUND: Continuing medical education for referring physicians is an essential
      part of raising the profile of plastic surgery and improving patient care. The
      authors conducted a prospective cohort study to assess the educational needs of
      emergency and primary care physicians who refer patients to the on-call plastic
      surgeon. METHODS: The following information was collected for telephone referrals
      from emergency and primary care physicians over a 1-year period: date, location
      of referral center, population of referral center, distance between referral
      center and tertiary care hospital, patient age, presenting problem, anatomical
      location of the problem, and treatment plan proposed by the plastic surgeon. In
      addition, the 50 physicians who most frequently referred patients were surveyed
      to identify which topics they perceived to be of the highest educational utility
      and which were frequently encountered. RESULTS: There were a total of 1077
      referrals to on-call plastic surgeons, mostly for trauma (83 percent) and
      injuries involved primarily the upper extremity (65 percent) or head and neck
      regions (26 percent). Five percent or more of all referrals involved mandible,
      phalangeal, metacarpal, or zygomatico-orbital complex fractures, minor burns,
      flexor tendon injuries, single digits requiring revision of an amputation, and
      extensor tendon injuries. Referring physicians reported that the topics of most
      educational utility were management of hand infections, minor burns, nasal
      fractures, boxer's fractures, complex facial lacerations, frostbite, metacarpal
      fractures, and scaphoid fractures. CONCLUSIONS: To have the greatest potential
      affect on changing physicians' behavior and improving patient care, continuing
      medical education should focus on traumatic injuries to the upper extremity and
      head and neck regions. A prioritized list of topics should include management of
      minor burns, hand fractures, hand infections, nasal infections, and complex
      facial lacerations.

PMID- 17440379
TI  - Human anatomy: the common denominator.

PMID- 17440380
TI  - Reoperations or revisions.

PMID- 17440381
TI  - Minds that think alike or cryptomnesia?

PMID- 17440384
TI  - Intraosseous "hemangiomas" are malformations and not tumors.

PMID- 17440388
TI  - Nonsurgical face lift.

PMID- 17440389
TI  - An objective system for measuring facial attractiveness.

PMID- 17440391
TI  - Age as an exclusion criterion for breast reconstruction.

PMID- 17440392
TI  - A rabbit model for capsular contracture: development and clinical implications.

PMID- 17440393
TI  - A simple barrier drape for breast implant placement.

PMID- 17440395
TI  - Physiology to improve surgical wound outcomes.

PMID- 17440396
TI  - Dielectric measurement in experimental burns: a new tool for burn depth
      determination.

PMID- 17440397
TI  - Reconstruction of an acquired subtotal ear defect with autogenous septal
      cartilage graft.

PMID- 17440398
TI  - The "cat's paw" retractor.

PMID- 17440399
TI  - Endonasal placement of spreader grafts.

PMID- 17440400
TI  - Alexandrite laser treatment of intraoral venous vascular malformations.

PMID- 17440401
TI  - The "intramuscular" rectus abdominis pedicle.

PMID- 17440402
TI  - Late results of burn wound scar after cerium nitrate-silver sulfadiazine and
      compressive therapy: scanning electron microscopy evaluation of a keloid scar.

PMID- 17440404
TI  - A technique for atraumatic microvascular arterial coupling.

PMID- 17440403
TI  - Mammalian bite wounds: is primary repair safe?

PMID- 17440405
TI  - Augmentation or reduction of plastic surgery training in the United kingdom:
      should we embrace or oppose nurses operating independently?

PMID- 17440406
TI  - Fat necrosis and dermolipectomy.

PMID- 17440407
TI  - Putting the umbilicus in the midline.

PMID- 17440408
TI  - A simple technique to correct umbilicus vertical malposition.

PMID- 17440409
TI  - The role of amputation in treating large Basal cell carcinomas of the extremity.

PMID- 17440410
TI  - Linburg-Comstock anomaly: seems to be harmless but may be fatal.

PMID- 17440411
TI  - Major nerve injuries associated with carpal tunnel release.

PMID- 17440412
TI  - The role of vacuum-assisted wound closure in blast injury.

PMID- 17440413
TI  - Omental transplantation for critical limb ischemia in Buerger's disease.

PMID- 17440414
TI  - Hyperbaric oxygen therapy is not a miracle.

PMID- 17440415
TI  - Bull's-eye technique to clear margins in nonmelanoma skin cancer.

PMID- 17440416
TI  - Flash fires during facial surgery: recommendations for the safe delivery of
      oxygen.

PMID- 17440417
TI  - Inspection criteria for the American Association for the Accreditation of
      Ambulatory Surgery Facilities.

PMID- 17440418
TI  - Extravascular lung water after pneumonectomy and one-lung ventilation in sheep.
AB  - OBJECTIVE: To compare the single thermodilution and the thermal-dye dilution
      techniques with postmortem gravimetry for assessment of changes in extravascular
      lung water after pneumonectomy and to explore the evolution of edema after
      injurious ventilation of the left lung. DESIGN: Experimental study. SETTING:
      University laboratory. SUBJECTS: A total of 30 sheep weighing 35.6 +/- 4.6 kg.
      The study included two parts: a pneumonectomy study (n = 18) and an injurious
      ventilation study (n = 12). METHODS: Sheep were anesthetized and mechanically
      ventilated with an FiO2 of 0.5, tidal volume of 6 mL/kg, and positive end
      expiratory pressure of 2 cm H2O. In the pneumonectomy study, sheep were assigned
      to right-sided pneumonectomy (n = 7), left-sided pneumonectomy (n = 7), or
      lateral thoracotomy only (sham operation, n = 4). In the injurious ventilation
      study, right-sided pneumonectomy was followed by ventilation with a tidal volume
      of 12 mL/kg and positive end-expiratory pressure of 0 cm H2O (n = 6) or by
      ventilation with a tidal volume of 6 mL/kg and positive end-expiratory pressure
      of 2 cm H2O for 4 hrs (n = 6). Volumetric variables, including extravascular lung
      water index (EVLWI), were measured with single thermodilution (STD; EVLWI(STD))
      and thermal-dye dilution (TDD; EVLWI(TDD)) techniques. We monitored pulmonary
      hemodynamics and respiratory variables. After the sheep were killed, EVLWI was
      determined for each lung by gravimetry (EVLWI(G)). RESULTS: In total, the study
      yielded strong correlations of EVLWI(STD) and EVLWI(TDD) with EVLWI(G) (n = 30; r
      = .83 and .94, respectively; p < .0001). After pneumonectomy, both the left- and
      the right-sided pneumonectomy groups displayed significant decreases in
      EVLWI(STD) and EVLWI(TDD). The injuriously ventilated sheep demonstrated
      significant increases in EVLWI that were detected by both techniques. The mean
      biases (+/-2 SD) compared with EVLWI(G) were 3.0 +/- 2.6 mL/kg for EVLWI(STD) and
      0.4 +/- 1.6 mL/kg for EVLWI(TDD). CONCLUSIONS: After pneumonectomy and injurious
      ventilation of the left lung, TDD and STD displayed changes in extravascular lung
      water with acceptable accuracy when compared with postmortem gravimetry.
      Ventilator-induced lung injury seems to be a crucial mechanism of pulmonary edema
      after pneumonectomy.

PMID- 17440419
TI  - Acute effects of combined high-frequency oscillation and tracheal gas
      insufflation in severe acute respiratory distress syndrome.
AB  - OBJECTIVE: In acute respiratory distress syndrome (ARDS), high-frequency
      oscillation (HFO) improves oxygenation relative to conventional mechanical
      ventilation (CMV). Alveolar ventilation is improved by adding tracheal gas
      insufflation (TGI) to CMV. We hypothesized that combined HFO and TGI (HFO-TGI)
      might result in improved gas exchange relative to both standard HFO and CMV
      according to the ARDS Network protocol. DESIGN: Prospective, randomized,
      crossover study. SETTING: A 30-bed university intensive care unit. PATIENTS: A
      total of 14 patients with early (<72 hrs in duration), severe (PaO2/FiO2 of <150
      mm Hg and prerecruitment oxygenation index of 22.8 +/- 1.9 [mean +/- SEM]),
      primary ARDS. INTERVENTIONS: Patients were ventilated with HFO without (60 mins)
      and combined with TGI (6.1 +/- 0.1 L/min, 60 mins) in random order. HFO sessions
      were repeated in inverse order within 24 hrs. HFO sessions were preceded and
      followed by ARDS Network CMV. Four recruitment maneuvers were performed during
      the study period. During HFO sessions, mean airway pressure was set at 1 cm H2O
      above the point of maximal curvature of the respiratory system expiratory
      pressure-volume curve. MEASUREMENTS AND MAIN RESULTS: Gas exchange and
      hemodynamics were determined before, during, and after HFO sessions. HFO-TGI
      improved PaO2/FiO2 relative to HFO and CMV (174.5 +/- 10.4 vs. 136.0 +/- 10.0 and
      105.0 +/- 3.7 mm Hg, respectively, p < .05 for both) and oxygenation index
      relative to HFO (17.1 +/- 1.3 vs. 22.3 +/- 1.7, respectively p < .05). PaO2/FiO2
      returned to baseline within 3 hrs after HFO. During HFO-TGI, shunt fraction and
      mixed venous oxygen saturation improved relative to CMV (0.36 +/- 0.01 vs. 0.45
      +/- 0.01 and 77.8% +/- 1.2% vs. 71.8% +/- 1.3%, respectively, p < .05 for both).
      PaCO2 and hemodynamics were unaffected by HFO sessions. Respiratory mechanics
      remained unchanged throughout the study period. CONCLUSIONS: In early onset,
      primary, severe ARDS, short-term HFO-TGI improves oxygenation relative to
      standard HFO and ARDS Network CMV.

PMID- 17440420
TI  - Randomization in clinical trials of titrated therapies: unintended consequences
      of using fixed treatment protocols.
AB  - OBJECTIVE: Clinical trial designs that randomize patients to fixed treatment
      regimens may disrupt preexisting relationships between illness severity and level
      of therapy. The practice misalignments created by such designs may have
      unintended effects on trial results and safety. METHODS: To illustrate this
      problem, the Transfusion Requirements in Critical Care (TRICC) trial and the
      Acute Respiratory Distress Syndrome Network low tidal volume (ARMA) trial were
      analyzed. RESULTS: Publications before TRICC indicated that clinicians used
      higher transfusion thresholds in patients with ischemic heart disease compared
      with younger, healthier patients (p = .001). The trial, however, randomized
      patients (n = 838) to liberal (10 g/dL hemoglobin) or restrictive (7 g/dL)
      transfusion thresholds. Thirty-day mortality was different and opposite in the
      liberal compared with the restrictive arm depending on presence (21 vs. 26%) or
      absence (25 vs. 16%) of ischemic heart disease (p = .03). At baseline in ARMA,
      consistent with prior publications, physicians set ventilator volumes lower in
      patients with high airway pressures and poor compliance (8.4-10.6 mL/kg
      interquartile range) than patients with less severe abnormalities (9.6-12 mL/kg)
      (p = .0001). In the trial, however, patients (n = 861) were randomized to low (6
      mL/kg) or high (12 mL/kg) tidal volumes. In patients with low compliance (<0.6
      mL/kg), 28-day mortality was higher when tidal volumes were raised rather than
      lowered (42 vs. 29%), but this effect was reversed in patients with higher
      compliance (21 vs. 37%; p = .003). CONCLUSIONS: In TRICC and ARMA, randomization
      to fixed treatment regimens disrupted preexisting relationships between illness
      severity and therapy level. This created noncomparable subgroups in both study
      arms that received care different and opposite from titrated care, that is,
      practice misalignments. These subgroups reduced the interpretability and safety
      of each trial. Characterizing current practice, incorporating current practice
      controls, and using alternative trial designs to minimize practice misalignments
      should improve trial safety and interpretability.

PMID- 17440421
TI  - Impact of delayed transfer of critically ill patients from the emergency
      department to the intensive care unit.
AB  - OBJECTIVE: Numerous factors can cause delays in transfer to an intensive care
      unit for critically ill emergency department patients. The impact of delays is
      unknown. We aimed to determine the association between emergency department
      "boarding" (holding admitted patients in the emergency department pending
      intensive care unit transfer) and outcomes for critically ill patients. DESIGN:
      This was a cross-sectional analytical study using the Project IMPACT database (a
      multicenter U.S. database of intensive care unit patients). Patients admitted
      from the emergency department to the intensive care unit (2000-2003) were
      included and divided into two groups: emergency department boarding >or=6 hrs
      (delayed) vs. emergency department boarding <6 hrs (nondelayed). Demographics,
      intensive care unit procedures, length of stay, and mortality were analyzed.
      Groups were compared using chi-square, Mann-Whitney, and unpaired Student's t
      tests. SETTING: Emergency department and intensive care unit. PATIENTS: Patients
      admitted from the emergency department to the intensive care unit (2000-2003).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Main outcomes were intensive
      care unit and hospital survival and intensive care unit and hospital length of
      stay. During the study period, 50,322 patients were admitted. Both groups
      (delayed, n = 1,036; nondelayed, n = 49,286) were similar in age, gender, and do
      not-resuscitate status, along with Acute Physiology and Chronic Health Evaluation
      II score in the subgroup for which it was recorded. Among hospital survivors, the
      median hospital length of stay was 7.0 (delayed) vs. 6.0 days (nondelayed) (p <
      .001). Intensive care unit mortality was 10.7% (delayed) vs. 8.4% (nondelayed) (p
      < .01). In-hospital mortality was 17.4% (delayed) vs. 12.9% (nondelayed) (p <
      .001). In the stepwise logistic model, delayed admission, advancing age, higher
      Acute Physiology and Chronic Health Evaluation II score, male gender, and
      diagnostic categories of trauma, intracerebral hemorrhage, and neurologic disease
      were associated with lower hospital survival (odds ratio for delayed admission,
      0.709; 95% confidence interval, 0.561-0.895). CONCLUSIONS: Critically ill
      emergency department patients with a >or=6-hr delay in intensive care unit
      transfer had increased hospital length of stay and higher intensive care unit and
      hospital mortality. This suggests the need to identify factors associated with
      delayed transfer as well as specific determinants of adverse outcomes.

PMID- 17440422
TI  - Tidal volume delivery during high-frequency oscillatory ventilation in adults
      with acute respiratory distress syndrome.
AB  - OBJECTIVE: a) Characterize how ventilator and patient variables affect tidal
      volume during high-frequency oscillatory ventilation; and b) measure tidal
      volumes in adults with acute respiratory distress syndrome during high-frequency
      oscillatory ventilation. DESIGN: Observational study. SETTING: Research
      laboratory and medical intensive care unit. PATIENTS: Test lung and patients with
      acute respiratory distress syndrome. INTERVENTIONS: Using a previously validated
      hot wire anemometer placed in series with a Sensormedics 3100B high-frequency
      ventilator, an endotracheal tube, and a test lung, tidal volume was measured at
      different combinations of frequency (4, 6, 8, 10, and 12 Hz), pressure amplitude
      (50, 60, 70, 80, and 90 cm H2O), mean airway pressure (20, 30, and 40 cm H2O),
      test lung compliance (10, 30, and 50 mL/cm H2O), endotracheal tube internal
      diameter (6, 7, and 8 mm), bias flow (20, 30, and 40 L/min), and
      inspiratory/expiratory ratio (1:2 and 1:1). In patients, tidal volume was
      measured at baseline ventilator settings and at baseline frequency +/-2 Hz and
      baseline pressure amplitude +/-10 cm H2O. MEASUREMENTS AND MAIN RESULTS: Measured
      tidal volumes were 23-225 mL during high-frequency oscillatory ventilation of the
      test lung. A 2-Hz increase in frequency and a 10-cm H2O increase in pressure
      amplitude caused a 21.3% +/- 4.1% decrease and 21.4% +/- 3.4% increase in tidal
      volume, respectively. Decreasing endotracheal tube internal diameter from 8 mm to
      7 mm and from 7 mm to 6 mm caused a 15.3% +/- 1.7% and 18.9% +/- 2.1% reduction
      in tidal volume, respectively. Increasing bias flow from 20 L/min to 30 L/min
      increased tidal volume by 11.2% +/- 3.9%. Further increases in bias flow, changes
      in compliance, and changes in mean airway pressure had little effect. Tidal
      volumes measured in acute respiratory distress syndrome patients were 44-210 mL.
      A 2-Hz increase in frequency was associated with a 23.1% +/- 6.3% decrease in
      tidal volume. In contrast to the test lung data, a 10-cm H2O increase in pressure
      amplitude resulted in only a 5.6% +/- 4.5% increase in tidal volume. CONCLUSIONS:
      Tidal volumes are not uniformly small during high-frequency oscillatory
      ventilation. The primary determinant of tidal volume in adults with acute
      respiratory distress syndrome during high-frequency oscillatory ventilation with
      the Sensormedics 3100B is frequency. Test lung findings suggest that endotracheal
      tube internal diameter is also an important determinant of tidal volume.

PMID- 17440423
TI  - Effect of interhospital transfer on resource utilization and outcomes at a
      tertiary care referral center.
AB  - OBJECTIVE: Mortality and length of stay are two outcome variables commonly used
      as benchmarks in rating the performance of medical centers. Acceptance of
      transfer patients has been shown to affect both outcomes and the costs of health
      care. Our objective was to compare observed and predicted lengths of stay,
      observed and predicted mortality, and resource consumption between patients
      directly admitted and those transferred to the intensive care unit (ICU) of a
      large academic medical center. DESIGN: Observational cohort study. SETTING: Mixed
      medical/surgical ICU of a university hospital. PATIENTS: A total of 4,569
      consecutive patients admitted to a tertiary care ICU from April 1, 1997, to March
      30, 2000. INTERVENTIONS: None. MEASUREMENTS: Acute Physiology and Chronic Health
      Evaluation (APACHE) III score, actual and predicted ICU and hospital lengths of
      stay, actual and predicted ICU and hospital mortality, and costs per admission.
      MAIN RESULTS: Crude comparison of directly admitted and transfer patients
      revealed that transfer patients had significantly higher APACHE III scores (mean,
      60.5 vs. 49.7, p < .001), ICU mortality (14% vs. 8%, p < .001), and hospital
      mortality (22% vs. 14%, p < .001). Transfer patients also had longer ICU lengths
      of stay (mean, 6.0 vs. 3.8 days, p < .001) and hospital lengths of stay (mean, 20
      vs. 15.9 days, p < .001). Stratified by disease severity using the APACHE III
      model, there was no difference in either ICU or hospital mortality between the
      two populations. However, in the transfer group with the lowest predicted
      mortality of 0-20%, ICU and hospital lengths of stay were significantly higher.
      In crude cost analysis, transfer patients' costs were $9,600 higher per ICU
      admission compared with nontransfer patients (95% confidence interval, $6,000
      $13,400). Risk stratification revealed that the higher per-patient cost was
      entirely confined to the transfer patients with the lowest predicted mortality.
      CONCLUSIONS: Patients transferred to a tertiary care ICU are generally more
      severely ill and consume more resources. However, they have similar adjusted
      mortality outcomes when compared with directly admitted patients. The difference
      in resource consumption is mainly attributable to the group of patients in the
      lowest predicted risk bracket.

PMID- 17440424
TI  - Tacrolimus: a new option in therapy-resistant chronic external otitis.
AB  - OBJECTIVE: To evaluate the efficacy of the novel topical immune modulator
      tacrolimus in chronic uninfectious otherwise therapy-resistant external otitis
      (EO). STUDY DESIGN: Prospective clinical study. PATIENTS AND METHODS: There were
      53 patients aged 5 to 83 years. An ear wick containing 0.1% tacrolimus ointment
      (Protopic) was inserted into the external auditory canal every 2nd to 3rd day.
      Altogether, the wick was changed three times. The pre-, intra- and
      posttherapeutic state of the clinical parameters otalgia, edema, otorrhea,
      erythema, pruritus, and desquamation was rated by means of a 6-point score
      system. Treatment efficiency was evaluated on the basis of follow-up
      investigations at 3-month intervals, a standardized findings sheet, and
      photograph documentation. RESULTS: The short-term results showed a clear
      improvement in 85% of the patients and significant reductions of the severity
      levels for all clinical parameters investigated (P < .001). Concerning the long
      term results, a one-time treatment cycle led to complete healing in 46% of the
      patients throughout a follow-up of 10 to 22 months. Of the patients, 54% had
      recurrent EO events with significantly extended mean symptom-free intervals.
      Reapplied tacrolimus treatment patterns attenuated the relapsing course of
      disease and significantly reduced the number of EO episodes. Within the
      observation period, no relevant side effects were observed, except for a local
      feeling of heat, occasional skin burning, and itching. CONCLUSIONS: The topical
      application of 0.1% tacrolimus ointment in the outer ear canal appears to be an
      effective and well-tolerated new option in corticosteroid-free treatment of
      chronic therapy-resistant EO.

PMID- 17440425
TI  - Important clinical symptoms in patients undergoing functional endoscopic sinus
      surgery for chronic rhinosinusitis.
AB  - OBJECTIVE: To evaluate the prevalence and severity of individual Rhinosinusitis
      Task Force (RSTF) symptoms in patients with chronic rhinosinusitis (CRS)
      undergoing functional endoscopic sinus surgery (FESS). METHODS: Retrospective
      analysis of prospectively collected data in 201 patients treated with FESS. The
      prevalence and severity of individual RSTF major and minor symptom scores graded
      on a visual analogue scale (VAS) were compared. Correlation between absolute
      improvement in individual symptom scores at 1-year postoperative was performed.
      RESULTS: One-hundred fifty-eight of 201 patients met inclusion criteria giving a
      response rate of 78%. The average age was 49.4 (range 18-80) with a male-to
      female ratio of 1.1:1. The preoperative leading mean symptom scores were
      postnasal drip (5.8 +/- 0.3), nasal obstruction (5.7 +/- 0.3), and facial
      congestion (5.1 +/- 0.3). These symptoms were also the most prevalent with 82%,
      84%, and 79% of patients reporting these symptoms, respectively. Postoperative
      symptom improvements were significant (P < .0001) across all RSTF domains except
      fever. The highest percentage improvement was seen with facial congestion (93%),
      nasal obstruction (92%), and postnasal drip (85%). Multivariate analysis revealed
      significant (P < .0001) high correlation between improvements of facial
      pain/pressure with facial congestion (R = 0.72), facial congestion with nasal
      obstruction (R = 0.65), and facial pain/pressure with headache (R = 0.72).
      CONCLUSION: The top three RSTF symptoms were postnasal drip, nasal obstruction,
      and facial congestion in terms of prevalence and severity. Symptom scores
      improved after FESS. Of these symptoms, the degree of improvement of facial
      pain/pressure, facial congestion, nasal obstruction, and headache are highly
      correlated.

PMID- 17440426
TI  - Radioimmunotherapy with astatine-211 using chimeric monoclonal antibody U36 in
      head and neck squamous cell carcinoma.
AB  - OBJECTIVES: In advanced head and neck squamous cell carcinoma (HNSCC), there is a
      need for an adjuvant treatment. We aim to evaluate the biodistribution and
      therapeutic effect of radioimmunotherapy using the alpha emitting, astatine-211
      labeled, chimeric monoclonal antibody U36 (U36) on the HNSCC cell line UT-SCC7 in
      vivo. STUDY DESIGN: Xenograft tumors were inoculated subcutaneously in nude mice.
      Astatine-211-labeled U36 was injected intravenously with or without blocking of
      target with nonlabeled U36. METHODS: In the biodistribution experiments,
      radioactivity was measured in tumors and various organs at set time points. In
      the therapeutic experiments, two groups (with or without blocking) received
      therapy, and the tumor growth was compared with that of controls. In addition,
      one group received nonlabeled U36 only. RESULTS: The biodistribution experiments
      demonstrated that astatine-211-labeled U36 could target UT-SCC7 xenografts in
      nude mice. With time, uptake increased in tumors and decreased in normal organs.
      Nonlabeled U36 did not influence tumor growth. In the two therapy groups, 18 of
      20 tumors responded to therapy by decreasing or stabilizing their volumes.
      Significant difference was seen between the treated groups and the controls (P <
      .05). CONCLUSION: The study illustrates the specific binding of astatine-211
      labeled U36 to HNSCC and suggests radioimmunotherapy with the alpha emitting
      radionuclide to be a useful treatment modality.

PMID- 17440427
TI  - Unusual delayed presentation of a nail gun injury through the skull base.
AB  - Published reports of nail gun injuries to the face are uncommon. We describe an
      unusual delayed presentation with injury through the infratemporal fossa and a
      literature review. A 55-year-old patient presented 2 weeks after an unrecognized
      injury with complaints of a headache. Imaging revealed a nail traversing the
      infratemporal fossa with intracranial extension. The nail was removed through a
      preauricular approach without sequelae. Nail gun missiles to the face are
      uncommon, dramatic, but often nonfatal because of their relative low velocity.
      Patients are usually diagnosed at the time of injury, evaluated with computed
      tomography and angiography, and treated with surgery.

PMID- 17440428
TI  - Failures of adenoidectomy for chronic rhinosinusitis in children: for whom and
      when do they fail?
AB  - OBJECTIVES: To determine which children who are treated with adenoidectomy for
      chronic rhinosinusitis (CRS) will ultimately undergo endoscopic sinus surgery
      (ESS) and the length of time between adenoidectomy and ESS. STUDY DESIGN:
      Retrospective chart review of prospectively collected data in a tertiary
      pediatric otolaryngology service. METHODS: One hundred forty-three children had
      adenoidectomy for CRS over a 10-year period. Follow-up was available on 121
      children. Sixty-one children failed the procedure. Data were available on 55
      children who underwent ESS after failing adenoidectomy for the treatment of CRS.
      Mean time from adenoidectomy to ESS was determined. Factors such as age, allergic
      rhinitis, asthma, computed tomography (CT) score, and sex were evaluated for
      effects on this time. RESULTS: With use of Cox regression analysis, the mean time
      from adenoidectomy to ESS was 24 months, ranging from 4 to 77 months. The
      presence of asthma (P < .04) and age less than 7 years (P < .01) were predictors
      of earlier failure. Allergic rhinitis (P < .3), CT score (P < .9), and sex (P <
      .3) showed no effect. CONCLUSIONS: Those who fail adenoidectomy for CRS who
      require ESS are mainly children who are younger than 7 years of age and have
      asthma. They appear to require a salvage ESS at a mean of 24 months after the
      adenoidectomy.

PMID- 17440429
TI  - Hepatocyte nuclear factor-1 alpha is associated with UGT1A1, UGT1A9 and UGT2B7
      mRNA expression in human liver.
AB  - Experimental evidence suggests HNF1alpha regulates UGT expression. This study
      investigates (1) whether the variability in HNF1alpha expression is associated
      with the variability in UGT1A1, UGT1A9 and UGT2B7 expression in human livers and
      (2) the functionality of 12 HNF1alpha variants using mRNA expression as
      phenotype. Controlling for known UGT variation in cis-acting elements known to
      affect UGT expression, we demonstrate that a combination of HNF1alpha mRNA levels
      and UGT genotype predicts variance in UGT expression to a higher extent than UGT
      genotype alone. None of the HNF1alpha polymorphisms studied, however, seem to
      have an effect on HNF1alpha, UGT1A1, UGT1A9 and UGT2B7 expression, ruling out
      their functional role. Our data provide evidence for HNF1alpha being a
      determinant of UGT1A1, UGT1A9 and UGT2B7 mRNA expression. However, the amount of
      UGT intergenotype variability explained by HNF1alpha expression appears to be
      modest, and further studies should investigate the role of multiple transcription
      factors.

PMID- 17440430
TI  - Rat survival to anthrax lethal toxin is likely controlled by a single gene.
AB  - We examined whether survival of different rat strains administered anthrax lethal
      toxin is genetically determined. A reproducible test population of first filial
      generation hybrid rats was bred based on the susceptibility of progenitors to
      anthrax lethal toxin and to maximize genetic diversity across the strains. These
      rats were then tested with varying doses of anthrax lethal toxin. We found that
      all 'sensitive' strains died within 2 h following systemic administration of 240
      mug/kg lethal toxin, while one strain survived following a five times higher dose
      (1.4 mg/kg). The ability of lethal toxin to lyse macrophage cultures derived from
      the bone marrow of these strains corresponded with in vivo results. We conclude
      that a rat test population can detect strain differences in response to anthrax
      lethal toxin. Survival is influenced by the host genome background and is likely
      due to a single gene with a recessive mode of inheritance.

PMID- 17440431
TI  - Metabolomic mapping of atypical antipsychotic effects in schizophrenia.
AB  - Schizophrenia is associated with impairments in neurotransmitter systems and
      changes in neuronal membrane phospholipids. Several atypical antipsychotic drugs
      induce weight gain and hypertriglyceridemia. To date, there has not been a
      comprehensive evaluation and mapping of global lipid changes in schizophrenia,
      and upon treatment with antipsychotics. Such mapping could provide novel insights
      about disease mechanisms and metabolic side effects of therapies used for its
      treatment. We used a specialized metabolomics platform 'lipidomics' that
      quantifies over 300 polar and nonpolar lipid metabolites (across seven lipid
      classes) to evaluate global lipid changes in schizophrenia and upon treatment
      with three commonly used atypical antipsychotics. Lipid profiles were derived for
      50 patients with schizophrenia before and after treatment for 2-3 weeks with
      olanzapine (n=20), risperidone (n=14) or aripiprazole (n=16). Patients were
      recruited in two cohorts (study I, n=27 and study II, n=23) to permit an internal
      replication analyses. The change from baseline to post-treatment was then
      compared among the three drugs. Olanzapine and risperidone affected a much
      broader range of lipid classes than aripiprazole. Approximately 50 lipids tended
      to be increased with both risperidone and olanzapine and concentrations of
      triacylglycerols increased and free fatty acids decreased with both drugs but not
      with aripiprazole. Phosphatidylethanolamine concentrations that were suppressed
      in patients with schizophrenia were raised by all three drugs. Drug specific
      differences were also detected. A principal component analysis (PCA) identified
      baseline lipid alterations, which correlated with acute treatment response. A
      more definitive long-term randomized study of these drugs correlating global
      lipid changes with clinical outcomes could yield biomarkers that define drug
      response phenotypes.

PMID- 17440432
TI  - Expression profiling in monozygotic twins discordant for bipolar disorder reveals
      dysregulation of the WNT signalling pathway.
AB  - To identify genes dysregulated in bipolar disorder (BD1), we carried out global
      gene expression profiling using whole-genome microarrays. To minimize genetic
      variation in gene expression levels between cases and controls, we compared
      expression profiles in lymphoblastoid cell lines from monozygotic twin pairs
      discordant for the disease. We identified 82 genes that were differentially
      expressed by >or=1.3-fold in three BD1 cases compared to their co-twins, and
      which were statistically (P<or=0.05) differentially expressed between the groups
      of BD1 cases and controls. Using quantitative reverse transcriptase-polymerase
      chain reaction, we confirmed the differential expression of some of these genes,
      including: KCNK1, MAL, PFN2, TCF7, PGK1 and PI4KCB, in at least two of the twin
      pairs. In contrast to the findings of a previous study by Kakiuchi and colleagues
      with similar discordant BD1 twin design, our data do not support the
      dysregulation of XBP1 and HSPA5. From pathway and gene ontology analysis, we
      identified upregulation of the WNT signalling pathway and the biological process
      of apoptosis. The differentially regulated genes and pathways identified in this
      study may provide insights into the biology of BD1.

PMID- 17440433
TI  - TGFB-induced factor (TGIF): a candidate gene for psychosis on chromosome 18p.
AB  - Schizophrenia (SC) and bipolar disorder (BP) share many clinical features, among
      them psychosis. We previously identified a putative gene locus for psychosis on
      chromosome 18p in a sample from the Central Valley of Costa Rica (CVCR)
      population. The present study replicated the association to a specific allele of
      microsatellite marker D18S63 on 18p11.3, using a newly collected sample from the
      CVCR. A combined analysis of both samples, plus additional subjects, showed that
      this specific allele on D18S63, which lies within an intron on the TGFB-induced
      factor (TGIF) gene, is strongly associated (P-value=0.0005) with psychosis.
      Eleven additional SNP markers, spanning five genes in the region, were analyzed
      in the combined sample from the CVCR. Only the four SNPs within the TGIF gene
      were in strong linkage disequilibrium with D18S63 (D'=1.00). A specific haplotype
      for all five markers within the TGIF gene showed evidence of association (P
      value=0.011) to psychosis. A second, distinct haplotype, containing a newly
      identified nonsynonymous polymorphism in exon 5 of the TGIF gene, showed a
      nonsignificant trend towards association to psychosis (P-value=0.077). TGIF is
      involved in neurodevelopment, neuron survival and controls the expression of
      dopamine receptors. Altogether, our results point to the possible involvement of
      TGIF in the pathophysiology of psychotic disorders in the CVCR population.

PMID- 17440434
TI  - Significant correlation in linkage signals from genome-wide scans of
      schizophrenia and schizotypy.
AB  - Prior family and adoption studies have suggested a genetic relationship between
      schizophrenia and schizotypy. However, this has never been verified using linkage
      methods. We therefore attempted to test for a correlation in linkage signals from
      genome-wide scans of schizophrenia and schizotypy. The Irish study of high
      density schizophrenia families comprises 270 families with at least two members
      with schizophrenia or poor-outcome schizoaffective disorder (n=637). Non
      psychotic relatives were assessed using the structured interview for schizotypy
      (n=746). A 10-cM multipoint, non-parametric, autosomal genome-wide scan of
      schizophrenia was performed in Merlin. A scan of a quantitative trait comprising
      ratings of DSM-III-R criteria for schizotypal personality disorder in non
      psychotic relatives was also performed. Schizotypy logarithm of the odds (LOD)
      scores were regressed onto schizophrenia LOD scores at all loci, with adjustment
      for spatial autocorrelation. To assess empirical significance, this was also
      carried out using 1000 null scans of schizotypy. The number of jointly linked
      loci in the real data was compared to distribution of jointly linked loci in the
      null scans. No markers were suggestively linked to schizotypy based on strict
      Lander-Kruglyak criteria. Schizotypy LODs predicted schizophrenia LODs above
      chance expectation genome wide (empirical P=0.04). Two and four loci yielded
      nonparametric LOD (NPLs) >1.0 and >0.75, respectively, for both schizophrenia and
      schizotypy (genome-wide empirical P=0.04 and 0.02, respectively). These results
      suggest that at least a subset of schizophrenia susceptibility genes also affects
      schizotypy in non-psychotic relatives. Power may therefore be increased in
      molecular genetic studies of schizophrenia if they incorporate measures of
      schizotypy in non-psychotic relatives.

PMID- 17440435
TI  - The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia.
AB  - Evidence suggests that myelin alterations could predispose to schizophrenia.
      Reduced expression of several myelin genes has been observed in schizophrenia
      patients. Recently, we identified the discoidin domain receptor 1 (DDR1; located
      at human chromosome 6p21.3) as a myelin gene in the mouse model and in a human
      oligodendroglial cell line. In the present study we screened for single
      nucleotide polymorphisms (SNPs) in the DNA from 100 schizophrenia patients. We
      identified a novel mutation within exon 10 that produces the amino-acid
      substitution N502S in the a-d isoforms, and M475V in the e isoform. However the
      frequency of the mutation (2%) was similar in schizophrenia patients and in
      control subjects. In a case-control assessment with 389 schizophrenic patients
      and 615 controls, we identified one SNP (SNP9, rs1049623) associated with
      schizophrenia (odds ratio=1.44, 95% confidence interval: 1.15-1.79, adjusted
      P=0.0016). This association was confirmed in haplotype analysis; the SNPs 9-10-11
      (rs1049623, rs2267641 and rs2239518) haplotype remaining significant even after
      adjustment for multiple testing (adjusted P=0.0136). Of note was a strong gender
      dependence in the association, that is, statistical significance restricted to
      men (adjusted P-value=0.0002). Regression analysis of DDR1 mRNA expression in
      peripheral blood lymphocytes from schizophrenia patients showed that the presence
      of the G allele significantly decreased the relative number of mRNA copies in a
      dose-dependent manner (P=0.003). These data suggest that the risk haplotype tags
      a cis-acting variant involved in the transcription regulation system of the gene.
      In conclusion, we propose the DDR1 as a new susceptibility gene for
      schizophrenia.

PMID- 17440436
TI  - Neuregulin1-induced cell migration is impaired in schizophrenia: association with
      neuregulin1 and catechol-o-methyltransferase gene polymorphisms.
AB  - Neuregulin1 (NRG1), a candidate susceptibility gene for schizophrenia, plays a
      critical role in neuronal migration and central nervous system development.
      However, its relation to schizophrenia pathogenesis is unknown. Here we show that
      B lymphoblasts migrate to NRG1 through the ErbB-signaling system as observed in
      neuronal cells. We assessed NRG1-induced cell migration in B lymphoblasts from
      patients with schizophrenia and found that NRG1-induced migration is
      significantly decreased compared with control individuals in two independent
      cohorts. This impaired migration is related at least in part to reduced AKT
      phosphorylation in the patients. Moreover, the magnitude of NRG1-induced
      migration is associated with polymorphisms of the NRG1 and catechol-o
      methyltransferase genes and with an epistatic interaction of these genes. This
      study demonstrates that the migratory response of schizophrenia-derived cells to
      NRG1 is impaired and is associated with genetic variations in more than one
      schizophrenia susceptibility gene, providing a novel insight into potential
      neurodevelopmental mechanisms of schizophrenia.

PMID- 17440437
TI  - New genes associated with schizophrenia in neurite formation: a review of cell
      culture experiments.
AB  - New genes consistently associated with schizophrenia include NRG1, Akt, DISC-1
      and dysbindin-1. Since these genes participate in neurotransmission,
      neuroplasticity and neurodevelopment it has not been easy to elucidate which of
      these roles are abnormal in patients with schizophrenia. Neurite formation is
      identified as a crucial stage in development, and it is proposed that a defect in
      neurite formation originating from abnormally encoded proteins by these new genes
      could be at least an in vitro marker that reflects the most consistent molecular
      and neuroanatomical findings in schizophrenia. A systematic review of the
      literature linking the process of neurite formation to genes with replicated
      evidence that supported their association with schizophrenia was conducted. In
      addition, an outline of the process of neurite formation was included. Neurite
      formation was shown to be induced by neuregulins, the product of the gene NRG1.
      The activation of Akt, a serine/threonine kinase, promoted neurite formation in
      six independent studies. Conversely, two studies found that Akt inhibits neurite
      outgrowth. Stronger evidence supporting an association with the new genes related
      to schizophrenia and neurite formation comes from DISC-1. Defects in DISC-1
      protein were shown to directly alter the process of neurite formation. Dysbindin
      1 has not yet been directly implicated in neurite outgrowth. These findings
      suggest that the proteins encoded by NRG1, Akt and DISC-1 are implicated in the
      process of neurite formation in cellular models as well as, at least in part,
      animal models during development. Abnormalities in this process could have
      potential etiologic implications for schizophrenia. Direct evidence, however, of
      abnormal neurite formation in patients with schizophrenia is still missing.
      Limitations to this model are identified.

PMID- 17440438
TI  - Modified Pfannenstiel approach for radical retropubic prostatectomy: a 3-year
      experience.
AB  - A modified Pfannenstiel approach for radical retropubic prostatectomy (RRP) has
      been described previously. We present our experience with this approach for
      performing a RRP over the past 3 years. Between January 2003 and July 2006, 544
      consecutive RRPs by modified Pfannenstiel approach between January 2003 and July
      2006 were performed. We analyzed blood loss, transfusions, use of drain, pain
      score, analgesia and hospital stay. Patients were followed up at 6 weeks, three
      monthly for a year and six monthly thereafter. All clinical and operative
      variables were entered into a database and analyzed. A total of 544 men underwent
      RRP with median follow-up of 11 (s.d.+/-10.5) months. The mean age was 60 (s.d.+/
      7) years. About 83, 91 and 95% of patients had nerve sparing, bladder neck
      preservation and a lymph node dissection, respectively. Fifty-three patients had
      a concurrent inguinal hernia repair through the same incision. Mean estimated
      blood loss was 431 (s.d.+/-267) ml. The pathological staging distribution was T2,
      82%; T3a, 9%; and T3b, 9%. The mean pain score at days 1 and 7 were 3.7 (s.d.+/
      2.5) and 3.3 (s.d.+/-3), respectively. The median hospital stay was 36 h (s.d.+/
      24). About 5.5% have had biochemical recurrence. At 12 months 97% were continent
      and 46% potent. RRP using a modified Pfannenstiel approach offers safety and
      efficacy. It facilitates repair of associated inguinal hernia through the same
      incision.

PMID- 17440439
TI  - Androgen receptor CAG repeat length contraction in diseased and non-diseased
      prostatic tissues.
AB  - To investigate contraction of CAG repeats within the androgen receptor gene (AR)
      as shorter CAG repeats have been implicated as a possible risk factor in prostate
      cancer (PCa). AR CAG repeat lengths were analyzed in DNA from microdissected
      diseased prostates, leukocytes from matched peripheral blood, and control non
      diseased prostates. Consistently, all prostatic tissues, whether from benign or
      cancerous areas of diseased prostates, or from control prostates, showed multiple
      AR CAG repeat contractions. Germline DNA from blood leukocytes had single CAG
      repeat lengths in the normal range. AR CAG repeat length contraction may be
      involved in prostate carcinogenesis and may precede the pathological process.

PMID- 17440440
TI  - A dual role of EGFR protein tyrosine kinase signaling in ubiquitination of AAV2
      capsids and viral second-strand DNA synthesis.
AB  - A 52 kd cellular protein, FK506-binding protein (FKBP52), phosphorylated at
      tyrosine residues by epidermal growth factor receptor protein tyrosine kinase
      (EGFR-PTK), inhibits adeno-associated virus 2 (AAV2) second-strand DNA synthesis
      and transgene expression. FKBP52 is dephosphorylated at tyrosine residues by T
      cell protein tyrosine phosphatase (TC-PTP), and TC-PTP over-expression leads to
      improved viral second-strand DNA synthesis and improved transgene expression. In
      these studies, we observed that perturbation of EGFR-PTK signaling by a specific
      inhibitor, Tyrphostin 23 (Tyr23), augmented the transduction efficiency of the
      single-stranded AAV (ssAAV) vector as well as the self-complementary AAV (scAAV)
      vector. Similarly, tyrosine-dephosphorylation of FKBP52 by TC-PTP resulted in
      increased transduction by both vectors. These data suggested that EGFR-PTK
      signaling also affects aspects of AAV transduction other than viral second-strand
      DNA synthesis. We document that inhibition of EGFR-PTK signaling leads to
      decreased ubiquitination of AAV2 capsids which, in turn, facilitates nuclear
      transport by limiting proteasome-mediated degradation of AAV vectors. We also
      document that Tyr23-mediated increase in AAV2 transduction efficiency is not
      further enhanced by a specific proteasome inhibitor, MG132. Thus, EGFR-PTK
      signaling modulates ubiquitin (Ub)/proteasome pathway-mediated intracellular
      trafficking as well as FKBP52-mediated second-strand DNA synthesis of AAV2
      vectors. This has implications in the optimal use of AAV vectors in gene therapy.

PMID- 17440441
TI  - Systemic and specific delivery of small interfering RNAs to the liver mediated by
      apolipoprotein A-I.
AB  - Tissue-targeted delivery of small interfering RNA (siRNA) must be achieved before
      RNA interference (RNAi) technology can be used in practical therapeutic
      approaches. In this study, the potential of apolipoprotein A-I (apo A-I) for the
      systemic delivery of nucleic acids to the liver is demonstrated using real-time
      in vivo imaging. As a proof of concept, synthetic siRNAs against hepatitis B
      virus (HBV) were formulated into complexes of apo A-I and 1,2-dioleoyl-3
      trimethylammonium-propane (DOTAP)/cholesterol (DTC-Apo) and injected
      intravenously (i.v.) into a mouse model carrying replicating HBV. We show that
      administration of these nanoparticles can significantly reduce viral protein
      expression by receptor-mediated endocytosis. The advantages of the apo A-I
      mediated siRNA delivery method are its liver specificity, its effectiveness at
      low doses (< or = 2 mg/kg) in only a single treatment, and its persistent
      antiviral effect up to 8 days. The liver-targeted gene silencing was also shown
      by in vivo images, in which bioluminescent signals emitted from the liver were
      efficiently reduced after i.v. administration of luciferase-specific siRNA and
      DTC-Apo lipoplex. Thus, our unique approach to siRNA delivery creates a
      foundation for the development of a new class of promising therapeutics against
      hepatitis viruses or hepatocyte genes related to tumor growth.

PMID- 17440442
TI  - Messenger RNA as a source of transposase for sleeping beauty transposon-mediated
      correction of hereditary tyrosinemia type I.
AB  - The Sleeping Beauty (SB) transposon system mediates chromosomal integration and
      stable gene expression when an engineered SB transposon is delivered along with
      transposase. One concern in the therapeutic application of the SB system is that
      persistent expression of transposase could result in transposon instability and
      genotoxicity. Here, we tested the use of transposase-encoding RNA plus transposon
      DNA for correction of murine fumarylacetoacetate hydrolase (FAH) deficiency. A bi
      functional transposon containing both mouse FAH and firefly luciferase sequences
      was used to track the growth of genetically corrected liver tissue by in vivo
      bioluminescence imaging after delivery of DNA or RNA as a source of transposase.
      Supplying SB transposase in the form of RNA resulted in selective repopulation of
      corrected hepatocytes with stable expression of FAH and luciferase. Plasma
      succinylacetone and amino acid levels were normalized, suggesting normal liver
      metabolism of catabolized protein products. Secondary FAH-deficient animals
      transplanted with hepatocytes (250,000) isolated from primary treated animals
      survived 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione (NTBC)
      withdrawal, gained weight consistently, and demonstrated stable expression of
      luciferase. We conclude that transposase-encoding messenger RNA (mRNA) can be
      used to mediate stable non-viral gene therapy, resulting in complete phenotypic
      correction, and is thus an effective source of recombinase activity for use in
      human gene therapy.

PMID- 17440443
TI  - Comparison of HIV-derived lentiviral and MLV-based gammaretroviral vector
      integration sites in primate repopulating cells.
AB  - The potential for leukemia caused by retroviral vector integration has become a
      significant concern for hematopoietic stem cell gene therapy. We analyzed the
      distribution of vector integrants in pigtailed macaque and baboon repopulating
      cells for the two most commonly used retroviral vector systems, human
      immunodeficiency virus (HIV)-based lentiviral vectors and murine leukemia virus
      (MLV)-based gammaretroviral vectors, to help define their relative genotoxicity.
      All animals had polyclonal engraftment with no apparent adverse effects from
      transplantation with gene-modified cells. In all, 380 MLV and 235 HIV unique
      vector integration sites were analyzed and had distinct distribution patterns in
      relation to genes and CpG islands as observed in previous in vitro studies. Both
      vector types were found more frequently in and near proto-oncogenes in
      repopulating cells than in a random dataset. Analysis of functional classes of
      genes with integrants within 100 kilobases (kb) of their transcription start
      sites showed an over-representation of genes involved in growth or survival near
      both lentiviral and gammaretroviral integrants. Microarray analysis showed that
      both gammaretroviral and lentiviral vectors were found close to genes with high
      expression levels in primitive cells enriched for hematopoietic stem cells. These
      data help define the relative risk of insertional mutagenesis with MLV-, HIV-,
      and simian immunodeficiency virus (SIV)-based vectors in a highly relevant
      primate model.

PMID- 17440444
TI  - Transgene persistence and cell turnover in the diarthrodial joint: implications
      for gene therapy of chronic joint diseases.
AB  - Local gene therapy for chronic joint diseases requires prolonged transgenic
      expression, but this has not been reliably achieved in animal models. Using
      normal and immunocompromised animals, we examined the capacity of various cell
      types in joint tissues to maintain and express exogenous transgenes after direct
      intra-articular gene delivery. We found that transgenic expression could persist
      for the lifetime of the animal but required precise immunological compatibility
      between the vector, transgene product, and host. It was not dependent on vector
      integration or promoter origin. We identified two phenotypically distinct sub
      populations of genetically modified cells within the joint: (i) transient cells,
      with a half-life of a few weeks, and (ii) stable cells that reside in the joint
      tissues indefinitely. Contrary to the prevailing assumption, the transient sub
      population was composed almost exclusively of synovial fibroblasts, indicating
      that the synovium is not an appropriate tissue upon which to base a long-term
      therapy. Instead, fibroblasts in the ligaments, tendons, and capsule emerged as
      the primary cell types capable of sustained therapeutic transgene expression.
      This study sheds new light on the cellular dynamics of articular tissues and
      suggests that cell turnover and immune reactivity are the key determinants in
      achieving sustained transgenic expression intra-articularly.

PMID- 17440445
TI  - Systemic administration of micro-dystrophin restores cardiac geometry and
      prevents dobutamine-induced cardiac pump failure.
AB  - Duchenne muscular dystrophy (DMD) is a fatal disease of striated muscle
      deterioration resulting from the loss of the cytoskeletal protein dystrophin.
      Most patients develop significant cardiomyopathy, with heart failure being the
      second leading cause of death in DMD. Compared with the extensive studies on
      skeletal muscle defects and potential therapy in DMD, very little attention has
      been directed at the increasing incidence of heart failure in DMD. Here we show
      that a single systemic injection of recombinant adeno-associated virus (rAAV2/6)
      harboring micro-dystrophin leads to extensive cardiac transduction, with micro
      dystrophin correctly localized at the periphery of the cardiac myocytes and
      functionally associated with the sarcolemmal membrane. Significantly, micro
      dystrophin gene transfer corrected the baseline end-diastolic volume defect in
      the mdx mouse heart and prevented cardiac pump failure induced by dobutamine
      stress testing in vivo, although several parameters of systolic function were not
      corrected. These results demonstrate that systemic gene delivery of micro
      dystrophin can restore ventricular distensibility and protect the mdx myocardium
      from pump dysfunction during adrenergic stimulation in vivo.

PMID- 17440446
TI  - The bigger picture.

PMID- 17440447
TI  - Cell lineage regulators in B and T cell development.
AB  - This special issue highlights a pivotal set of regulatory molecules that have
      emerged as central controllers of cell-type identity in the immune system. Each
      in its own way has been considered as a kind of 'master' regulator of a
      particular cell fate choice, but the actual modes of action of these factors vary
      widely. The comparison among them sheds light on the different ways that an
      essential regulatory input can affect cellular identity.

PMID- 17440448
TI  - Blimp-1 over Budapest.
AB  - Blimp-1 is a transcription factor that affects the expression of hundreds of
      genes in lymphocytes. Recent work confirmed its role in the maturation of B cells
      into immunoglobulin-secreting plasmablasts, as well as in the control of T cell
      homeostasis and tolerance. What follows is a short history of how Blimp-1 was
      discovered.

PMID- 17440449
TI  - Trawling for treasure: tales of T-bet.
AB  - Discovering the transcription factors that direct lineage commitment in the T
      helper cell was a formidable task. Laurie Glimcher describes how she and Susanne
      Szabo hunted down T-bet, a transcription factor that is a 'master regulator' of
      commitment to the T helper type 1 lineage.

PMID- 17440450
TI  - Regulation of lymphocyte development by Notch signaling.
AB  - Notch molecules are well conserved from Drosophila melanogaster to mammals and
      regulate a broad spectrum of various cell lineage commitment processes. Recent
      studies using inhibitors, transgenic mice and conditional loss-of-function
      approaches have demonstrated essential roles for Notch signaling in the
      differentiation of thymocytes and peripheral T cells, as well as B cells. Here we
      highlight parallels in the developmental regulation of mammalian lymphocytes and
      the D. melanogaster nervous system through Notch cooperation with the
      transcriptional regulators RBP-J (Su(H)), MINT (Hairless) and E2A (Ac-Sc-Da).

PMID- 17440451
TI  - Foxp3 in control of the regulatory T cell lineage.
AB  - Foxp3, an X chromosome-encoded forkhead transcription factor family member, is
      indispensable for the differentiation of regulatory T cells. These cells have a
      vital role in preventing autoimmunity and pathology inflicted by uncontrolled
      immune responses to infections. Deficiency or mutation in Foxp3 in humans and
      mice leads to an early onset, highly aggressive and fatal autoimmune disease
      affecting various tissues. Here, we review recent advances in our understanding
      of the Foxp3-dependent molecular and functional program and the role of Foxp3 in
      regulatory T cell biology.

PMID- 17440452
TI  - Pax5: the guardian of B cell identity and function.
AB  - The transcription factor Pax5 is essential for commitment of lymphoid progenitors
      to the B lymphocyte lineage. Pax5 fulfils a dual role by repressing B lineage
      'inappropriate' genes and simultaneously activating B lineage-specific genes.
      This transcriptional reprogramming restricts the broad signaling capacity of
      uncommitted progenitors to the B cell pathway, regulates cell adhesion and
      migration, induces V(H)-DJ(H) recombination, facilitates (pre-)B cell receptor
      signaling and promotes development to the mature B cell stage. Conditional Pax5
      inactivation in early and late B lymphocytes revealed an essential role for Pax5
      in controlling the identity and function of B cells throughout B lymphopoiesis.
      PAX5 has also been implicated in human B cell malignancies, as it is deregulated
      by chromosomal translocations in a subset of acute lymphoblastic leukemias and
      non-Hodgkin lymphomas.

PMID- 17440454
TI  - Incomplete screening?

PMID- 17440455
TI  - TLR9 and DNA 'feel' RAGE.

PMID- 17440456
TI  - Smads keep TABs on inflammation.

PMID- 17440457
TI  - Epithelial NF-kappaB maintains host gut microflora homeostasis.

PMID- 17440458
TI  - Giving B cell tolerance the 'TSLiP'.

PMID- 17440484
TI  - Highway to the inner nuclear membrane: rules for the road.
AB  - To enter the nucleus a protein must be chaperoned by a transport factor through
      the nuclear pore complex or it must be small enough to pass through by diffusion.
      Although these principles have long described the nuclear import of soluble
      proteins, recent evidence indicates that they also apply to the import of
      integral inner nuclear membrane proteins. Here we develop a set of rules that
      might govern the transport of proteins to the inner nuclear membrane.

PMID- 17440485
TI  - From dermal exposure to internal dose.
AB  - Exposure scenarios form an essential basis for chemical risk assessment reports
      under the new EU chemicals regulation REACH (Registration, Evaluation,
      Authorisation and restriction of Chemicals). In case the dermal route of exposure
      is predominant, information on both exposure and dermal bioavailability is
      necessary for a proper risk assessment. Various methodologies exist to measure
      dermal exposure, providing quantitative or semiquantitative information. Although
      these studies may provide very specific and relevant information, it should be
      realized that case by case in-depth exposure assessment would be a very expensive
      process. Dermal bioavailability data are most often obtained from in vitro
      studies or animal experiments. For the design of studies, which generate data
      relevant for chemical risk assessment, detailed information on the exposure
      conditions is crucial (skin surface exposed, exposure duration, dose and physical
      state of the chemical). Results from non-testing methods for skin absorption,
      such as (Q)SARs, have been used only to a very limited extent for regulatory
      purposes. Suggestions are made in order to extend the use these methods to dermal
      risk assessment of chemical substances, thereby improving the practicability of
      REACH.

PMID- 17440486
TI  - Exposure to fine particles (PM2.5 and PM1) and black smoke in the general
      population: personal, indoor, and outdoor levels.
AB  - Personal exposure to PM(2.5) and PM(1), together with indoor and residential
      outdoor levels, was measured in the general adult population (30 subjects, 23-51
      years of age) of Gothenburg, Sweden. Simultaneously, urban background
      concentrations of PM(2.5) were monitored with an EPA WINS impactor. The 24-h
      samples were gravimetrically analyzed for mass concentration and black smoke (BS)
      using a smokestain reflectometer. Median levels of PM(2.5) were 8.4 microg/m(3)
      (personal), 8.6 microg/m(3) (indoor), 6.4 microg/m(3) (residential outdoor), and
      5.6 microg/m(3) (urban background). Personal exposure to PM(1) was 5.4
      microg/m(3), while PM(1) indoor and outdoor levels were 6.2 and 5.2 microg/m(3),
      respectively. In non-smokers, personal exposure to PM(2.5) was significantly
      higher than were residential outdoor levels. BS absorption coefficients were
      fairly similar for all microenvironments (0.4-0.5 10(-5) m(-1)). Personal
      exposure to particulate matter (PM) and BS was well correlated with indoor
      levels, and there was an acceptable agreement between personal exposure and urban
      background concentrations for PM(2.5) and BS(2.5) (r(s)=0.61 and 0.65,
      respectively). PM(1) made up a considerable amount (70-80%) of PM(2.5) in all
      microenvironments. Levels of BS were higher outdoors than indoors and higher
      during the fall compared with spring. The correlations between particle mass and
      BS for both PM(2.5) vs. BS(2.5) and PM(1) versus BS(1) were weak for all
      microenvironments including personal exposure. The urban background station
      provided a good estimate of residential outdoor levels of PM(2.5) and BS(2.5)
      within the city (r(s)=0.90 and 0.77, respectively). Outdoor levels were
      considerably affected by long-range transported air pollution, which was not
      found for personal exposure or indoor levels. The within-individual (day-to-day)
      variability dominated for personal exposure to both PM(2.5) and BS(2.5) in non
      smokers.

PMID- 17440487
TI  - Method for determination of acephate, methamidophos, omethoate, dimethoate,
      ethylenethiourea and propylenethiourea in human urine using high-performance
      liquid chromatography-atmospheric pressure chemical ionization tandem mass
      spectrometry.
AB  - Because of increasing concern about widespread use of insecticides and
      fungicides, we have developed a highly sensitive analytical method to quantify
      urine-specific urinary biomarkers of the organophosphorus pesticides acephate,
      methamidophos, omethoate, dimethoate, and two metabolites from the fungicides
      alkylenebis-(dithiocarbamate) family: ethylenethiourea and propylenethiourea. The
      general sample preparation included lyophilization of the urine samples followed
      by extraction with dichloromethane. The analytical separation was performed by
      high-performance liquid chromatography (HPLC), and detection by a triple
      quadrupole mass spectrometer with and atmospheric pressure chemical ionization
      source in positive ion mode using multiple reaction monitoring and tandem mass
      spectrometry (MS/MS) analysis. Two different Thermo-Finnigan (San Jose, CA, USA)
      triple quadrupole mass spectrometers, a TSQ 7,000 and a TSQ Quantum Ultra, were
      used in these analyses; results are presented comparing the method specifications
      of these two instruments. Isotopically labeled internal standards were used for
      three of the analytes. The use of labeled internal standards in combination with
      HPLC-MS/MS provided a high degree of selectivity and precision. Repeated analysis
      of urine samples spiked with high, medium and low concentration of the analytes
      gave relative standard deviations of less than 18%. For all compounds the
      extraction efficiency ranged between 52% and 63%, relative recoveries were about
      100%, and the limits of detection were in the range of 0.001-0.282 ng/ml.

PMID- 17440490
TI  - Proliferating resident microglia after focal cerebral ischaemia in mice.
AB  - Cerebral ischaemia usually results in the rapid death of neurons within the
      immediate territory of the affected artery. Neuronal loss is accompanied by a
      sequence of events, including brain oedema, blood-brain barrier (BBB) breakdown,
      and neuroinflammation, all of which contribute to further neuronal death.
      Although the role of macrophages and mononuclear phagocytes in the expansion of
      ischaemic injury has been widely studied, the relative contribution of these
      cells, either of exogenous or intrinsic central nervous system (CNS) origin is
      still not entirely clear. The purpose of this study, therefore, was to use
      different durations of transient middle cerebral artery occlusion (tMCAo) in the
      mouse to investigate fully post-occlusion BBB permeability and cellular changes
      in the brain during the 72 h post-MCAo period. This was achieved using in vivo
      magnetic resonance imaging (MRI) and cell labelling techniques. Our results show
      that BBB breakdown and formation of the primary ischaemic damage after tMCAo is
      not associated with significant infiltration of neutrophils, although more are
      observed with longer periods of MCAo. In addition, we observe very few
      infiltrating exogenous macrophages over a 72 h period after 30 or 60 mins of
      occlusion, instead a profound increase in proliferating resident microglia cells
      was observed. Interestingly, the more severe injury associated with 60 mins of
      MCAo leads to a markedly reduced proliferation of resident microglial cells,
      suggesting that these cells may play a protective function, possibly through
      phagocytosis of infiltrating neutrophils. These data further support possible
      beneficial actions of microglial cells in the injured brain.

PMID- 17440491
TI  - Soluble epoxide hydrolase: a novel therapeutic target in stroke.
AB  - The P450 eicosanoids epoxyeicosatrienoic acids (EETs) are produced in brain and
      perform important biological functions, including protection from ischemic
      injury. The beneficial effect of EETs, however, is limited by their metabolism
      via soluble epoxide hydrolase (sEH). We tested the hypothesis that sEH inhibition
      is protective against ischemic brain damage in vivo by a mechanism linked to
      enhanced cerebral blood flow (CBF). We determined expression and distribution of
      sEH immunoreactivity (IR) in brain, and examined the effect of sEH inhibitor 12
      (3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester (AUDA-BE) on CBF and
      infarct size after experimental stroke in mice. Mice were administered a single
      intraperitoneal injection of AUDA-BE (10 mg/kg) or vehicle at 30 mins before 2-h
      middle cerebral artery occlusion (MCAO) or at reperfusion, in the presence and
      absence of P450 epoxygenase inhibitor N-methylsulfonyl-6-(2-propargyloxyphenyl)
      hexanamide (MS-PPOH). Immunoreactivity for sEH was detected in vascular and non
      vascular brain compartments, with predominant expression in neuronal cell bodies
      and processes. 12-(3-Adamantan-1-yl-ureido)-dodecanoic acid butyl ester was
      detected in plasma and brain for up to 24 h after intraperitoneal injection,
      which was associated with inhibition of sEH activity in brain tissue. Finally,
      AUDA-BE significantly reduced infarct size at 24 h after MCAO, which was
      prevented by MS-PPOH. However, regional CBF rates measured by iodoantipyrine
      (IAP) autoradiography at end ischemia revealed no differences between AUDA-BE-
      and vehicle-treated mice. The findings suggest that sEH inhibition is protective
      against ischemic injury by non-vascular mechanisms, and that sEH may serve as a
      therapeutic target in stroke.

PMID- 17440492
TI  - Glutamatergic and GABAergic neurotransmitter cycling and energy metabolism in rat
      cerebral cortex during postnatal development.
AB  - The contribution of glutamatergic and gamma-aminobutyric acid (GABA)ergic neurons
      to oxidative energy metabolism and neurotransmission in the developing brain is
      not known. Glutamatergic and GABAergic fluxes were assessed in neocortex of
      postnatal day 10 (P10) and 30 (P30) urethane-anesthetized rats infused
      intravenously with [1,6-(13)C(2)]glucose for different time intervals (time
      course) or with [2-(13)C]acetate for 2 to 3 h (steady state). Amino acid levels
      and (13)C enrichments were determined in tissue extracts ex vivo using (1)H
      [(13)C]-NMR spectroscopy. Metabolic fluxes were estimated from the best fits of a
      three-compartment metabolic model (glutamatergic neurons, GABAergic neurons, and
      astroglia) to the (13)C-enrichment time courses of amino acids from [1,6
      (13)C(2)]glucose, constrained by the ratios of neurotransmitter cycling (V(cyc))
      to-tricarboxylic acid (TCA) cycle flux (V(TCAn)) calculated from the steady-state
      [2-(13)C]acetate enrichment data. From P10 to P30 increases in total neuronal
      (glutamate plus GABA) TCA cycle flux (3 x ; 0.24+/-0.05 versus 0.71+/-0.07
      micromol per g per min, P<0.0001) and total neurotransmitter cycling flux (3.1 to
      5 x ; 0.07 to 0.11 (+/-0.03) versus 0.34+/-0.03 micromol per g per min, P<0.0001)
      were approximately proportional. Incremental changes in total cycling
      (DeltaV(cyc(tot))) and neuronal TCA cycle flux (DeltaV(TCAn(tot))) between P10
      and P30 were 0.23 to 0.27 and 0.47 micromol per g per min, respectively, similar
      to the approximately 1:2 relationship previously reported for adult cortex. For
      the individual neurons, increases in V(TCAn) and V(cyc) were similar in magnitude
      (glutamatergic neurons, 2.7 x versus 2.8 to 4.6 x ; GABAergic neurons,
      approximately 5 x versus approximately 7 x), although GABAergic flux changes were
      larger. The findings show that glutamate and GABA neurons undergo large and
      approximately proportional increases in neurotransmitter cycling and oxidative
      energy metabolism during this major postnatal growth spurt.

PMID- 17440493
TI  - Ex vivo programmed macrophages ameliorate experimental chronic inflammatory renal
      disease.
AB  - Macrophage infiltration of the kidney is a prominent feature associated with the
      severity of renal injury and progressive renal failure. To determine the
      influence of macrophages in renal disease models in the absence of endogenous T
      and B cells, we performed adoptive transfer of macrophages into severe combined
      immunodeficient (SCID) mice. In this study, macrophages were isolated from the
      spleens of BALB/c mice and stimulated with lipopolysaccharide to induce
      classically activated M1 macrophages or with interleukin-4 (IL-4) and IL-13 to
      induce alternatively activated M2 macrophages. These macrophages were then
      infused into SCID mice with adriamycin nephropathy; an in vivo model of chronic
      inflammatory renal disease analogous to human focal segmental glomerulosclerosis.
      Mice infused with M1 macrophages had a more severe histological and functional
      injury, whereas M2 macrophage-induced transfused mice had reduced histological
      and functional injury. Both M1 and M2 macrophages localized preferentially to the
      area of injury and maintained their phenotypes even after 4 weeks. The protective
      effect of M2 macrophages was associated with reduced accumulation and possibly
      downregulated chemokine and inflammatory cytokine expression of the host
      infiltrating macrophages. Our findings demonstrate that macrophages not only act
      as effectors of immune injury but can be induced to provide protection against
      immune injury.

PMID- 17440494
TI  - Vitamin D activates type A natriuretic peptide receptor gene transcription in
      inner medullary collecting duct cells.
AB  - Many clinical and animal studies suggest that vitamin D and its metabolites have
      beneficial effects in the cardiovascular and renal systems. Using immunologic and
      enzymatic assays, vitamin D receptor and 25 hydroxyvitamin D3 1alpha-hydroxylase
      activity were found in inner medullary collecting duct (IMCD) cells suggesting an
      autocrine/paracrine role in this nephron segment. In this study, we examined the
      ability of 1,25 dihydroxyvitamin D3 (1,25(OH)(2)D3) to regulate the expression of
      the vasculoprotective natriuretic peptide receptor-A gene in these cells in
      culture. Treatment of the cells with 1,25(OH)(2)D3 caused a doubling of
      natriuretic peptide-dependent cyclic guanosine monophosphate production and a
      significant increase in natriuretic peptide receptor-A protein expression. This
      was accompanied by significant increases in receptor mRNA levels and gene
      promoter activity. Mutation of a vitamin D response element, positioned upstream
      from the gene start site, resulted in a complete loss of 1,25(OH)(2)D3-dependent
      induction but not the induction by hypertonic stimuli. Introduction of small
      interfering RNA directed against the vitamin D receptor into the IMCD cells
      resulted in decreased natriuretic peptide receptor-A gene promoter activity and
      protein. The increase in this receptor expression may account for some of the
      reported beneficial effect of 1,25(OH)(2)D3 on the cardiovascular system and
      kidney.

PMID- 17440497
TI  - Comment on Gellekink et al.

PMID- 17440495
TI  - Chronic kidney disease management in the United Kingdom: NEOERICA project
      results.
AB  - Early identification of patients with chronic kidney disease (CKD) may allow
      health-care systems to implement interventions aimed at decreasing disease
      progression and eventual morbidity and mortality. Primary care in the United
      Kingdom is computerized suggesting a separate screening program for CKD may not
      be necessary because identifying data already populates primary care databases.
      Our study utilized a data set of 163 demographic, laboratory, diagnosis, and
      prescription variables from 130 226 adults in the regions of Kent, Manchester,
      and Surrey. The patients were 18 years of age and older in a 5-year study period
      culminating in November 2003. Estimated glomerular filtration rate was calculated
      from the four-variable Modification of Diet in Renal Disease equation using
      calibrated creatinine levels. A valid creatinine value was recorded in almost 30%
      of this cohort. The age-standardized prevalence of stage 3-5 CKD was 10.6% for
      females and 5.8% for males. In these patients, the odds ratio for hypertension
      was 2.1, for diabetes 1.33, and for cardiovascular disease 1.69. Only 20% of the
      diabetic people with stage 3-5 CKD had a blood pressure less than or equal to
      130/80 mm Hg. The proportion of patients with anemia significantly rose as renal
      function declined. We suggest that stage 3-5 CKD is easily detected in existing
      computerized records. The associated comorbidity and management is readily
      available enabling intervention and targeting of specialist resources.

PMID- 17440498
TI  - An explanation for another familial case of Rett syndrome: maternal germline
      mosaicism.
AB  - Rett syndrome (RTT; OMIM#312750) is a severe neurodevelopmental disorder that
      affects mainly girls. It has an estimated incidence of 1:10,000-15,000 females.
      Mutations in the X-linked gene methyl CpG-binding protein 2 (MECP2) have been
      found in most patients. The most accepted explanation for the sex bias is that
      the Rett mutation in sporadic cases has its origin in the paternal germline X
      chromosome and can thus only be transmitted to females. The majority of cases are
      sporadic (99.5%) but some familial cases have been described. These cases can
      either be explained by germline mosaicism or by asymptomatic carrier mothers with
      skewing of X-inactivation towards the wild-type MECP2 allele. We describe one of
      the few familial cases of RTT in which a maternal germline mosaicism is the most
      likely explanation. The mutation p.Arg270fs (c.808delC) was identified in both a
      girl with classical RTT and her brother who had the severe neurological phenotype
      usually described in males. The mutation was absent in DNA extracted from blood
      of both parents. These type of events must be taken into consideration in the
      genetic counselling of families after the diagnosis of a first case of RTT in a
      female or a MECP2 mutation in a male.

PMID- 17440499
TI  - Clinical outcome of preimplantation genetic diagnosis for cystic fibrosis: the
      Brussels' experience.
AB  - Preimplantation genetic diagnosis is an alternative for prenatal diagnosis that
      makes it possible to perform the diagnosis of a chromosomal or monogenic disorder
      at the preimplantation embryo level. Cystic fibrosis is one of the monogenic
      diseases for which PGD can be performed. In this study, we looked at the requests
      and PGD cycles for this particular disorder over an 11-year period. Sixty-eight
      percent of the requests eventually led to at least one complete PGD cycle. In 80%
      of the cycles, an embryo transfer was performed and an ongoing pregnancy was
      obtained in 22.2% of the cycles with oocyte retrieval. After embryo transfer, a
      couple had 27.8% chance of giving birth to a liveborn child. No misdiagnosis was
      recorded. The rate of perinatal deaths/stillborn children was relatively high,
      but no excess of major congenital anomalies was observed in the surviving
      children.

PMID- 17440500
TI  - A t(4;6)(q12;p23) translocation disrupts a membrane-associated O-acetyl
      transferase gene (MBOAT1) in a patient with a novel brachydactyly-syndactyly
      syndrome.
AB  - Here, we report a patient with a novel brachydactyly-syndactyly syndrome and a de
      novo translocation 46,XY,t(4;6)(q12;p23). We mapped the breakpoint and identified
      genes in the breakpoint region. One of the genes on chromosome 6, the membrane
      associated O-acetyl transferase gene 1 (MBOAT1), was disrupted by the breakpoint.
      This gene consists of 13 exons and encodes a protein of 495 amino acids. MBOAT1
      is predicted to be a transmembrane protein and belongs to the superfamily of
      membrane-bound O-acyltransferases. These proteins transfer organic compounds,
      usually fatty acids, onto hydroxyl groups of membrane-embedded targets.
      Identification of the transferred acyl group and the target may reveal the
      signaling pathways altered in this novel brachydactyly-syndactyly syndrome.

PMID- 17440501
TI  - Abstracts of the 15th European Congress on Obesity, Budapest, Hungary, 22-25
      April 2007.

PMID- 17440514
TI  - Age, period and birth cohort effects on prevalence of overweight and obesity in
      Australian adults from 1990 to 2000.
AB  - OBJECTIVE: To assess the individual contributions of age, period and birth cohort
      to prevalence of overweight and obesity in the Australian population during 1990
      to 2000. DESIGN: Age-period-cohort Poisson regression modelling of data from
      National Health Surveys conducted in Australia in 1990, 1995 and 2000. SUBJECTS:
      Adults aged 20 years and over. Weightings were applied to account for differences
      in sampling and participation rates so that the sample is representative of the
      entire Australian adult population. METHODS: Twelve age groups, based on 5-year
      intervals from 20 to 24 years to greater than 75 years, three survey periods and
      14 cohorts, also based on 5-year intervals from pre-1915 up to 1976-1980, were
      used in the analysis. The data were age-standardized to the 2000 population and
      body mass index (BMI) was calculated. Log-linear models, for the prevalence rates
      of overall overweight (BMI > or =25) and of obesity (BMI > or =30) were fitted to
      the data. RESULTS: Age (P<0.001), period (P<0.001) and cohort (P=0.002) all
      showed significant independent effects on prevalence of overall overweight in the
      Australian population such that prevalence rises with increasing age, recency of
      period and cohorts born since 1960. Age (P<0.001) and period (P<0.001)
      demonstrated strong effects on prevalence of obesity but birth cohort (P=0.07)
      was not significant. The effects were similar for men and women except that the
      overall effect of birth cohort on overall overweight was significant in women
      (P<0.05) but not men (P=0.09). CONCLUSION: The prevalence of overweight and
      obesity in Australian adults continued to rise during the 1990s. The obesogenic
      environment seems to have worsened and more recently born cohorts may be at
      increased risk of overweight.

PMID- 17440515
TI  - Accuracy of the Actiheart for the assessment of energy expenditure in adults.
AB  - BACKGROUND/OBJECTIVE: The Actiheart (Mini Mitter, Sunriver, OR, USA) uses heart
      rate (HR) and activity data to predict activity energy expenditure (AEE).
      Currently, the Actiheart has only been tested during laboratory conditions.
      Therefore, the objective of this study was to validate the Actiheart prediction
      method against indirect calorimetry during a wide range of activities in a field
      setting. SUBJECTS/METHODS: Forty-eight participants (age: 35+/-11.4 years) were
      recruited for the study. Eighteen activities were split into three routines of
      six activities and each routine was performed by 20 participants. During each
      routine, the participants wore an Actiheart and simultaneously, AEE was measured
      with a Cosmed K4b(2) portable metabolic system. The manufacturer's HR algorithm,
      activity algorithm, and combined activity and HR algorithm were used to estimate
      AEE. RESULTS: The mean error (and 95% prediction intervals) for the combined
      activity and HR algorithm, HR algorithm, and activity algorithm versus the Cosmed
      K4b(2) were 0.02 kJ kg(-1) min(-1) (-0.17, 0.22 kJ kg(-1) min(-1)), -0.03 kJ kg(
      1) min(-1) (-0.24, 0.18 kJ kg(-1) min(-1)), and 0.14 kJ kg(-1) min(-1) (-0.12,
      0.40 kJ kg(-1) min(-1)), respectively. CONCLUSION: The Actiheart combined
      activity and HR algorithm and HR algorithm provide similar estimates of AEE on
      both a group and individual basis.

PMID- 17440516
TI  - Food sources of plant sterols in the EPIC Norfolk population.
AB  - OBJECTIVE: To investigate the intake of plant sterols and identify major dietary
      sources of plant sterols in the British diet. SUBJECTS: A total of 24 798 men and
      women recruited during 1993-1997, participating in the European Prospective
      Investigation into Cancer (EPIC-Norfolk). INTERVENTIONS: A database of the plant
      sterol (campesterol, beta-sitosterol, stigmasterol, campestanol and beta
      sitostanol) content in foods, based on gas-liquid chromatography (GLC) analyses,
      was linked to nutritional intake data from food frequency questionnaires in the
      EPIC-Norfolk population. RESULTS: The mean (s.d.) intake of total plant sterols
      was 300 (108) mg/d for men and 293 (100) mg/d for women. Bread and other cereals,
      vegetables and added fats were the three major food sources of plant sterols
      representing 18.6 (8.9), 18.4 (8.5) and 17.3 (10.4)% of the total plant sterol
      intake respectively. Women had a higher plant sterol density than men (36.4 vs
      32.8 mg/1000 kJ, P<0.001) and in relation to energy intake higher intakes of
      plant sterols from vegetables, bread and other cereals, added fats, fruits and
      mixed dishes (all P<0.001), whilst men had higher intakes of plant sterols from
      cakes, scones and chocolate, potatoes (all P<0.001) and other foods (P<0.01).
      CONCLUSIONS: The intake of plant sterols in UK, mainly from bread, cereals, fats
      and vegetables, is much higher than previously reported but comparable to recent
      European studies.

PMID- 17440517
TI  - Why so thin?

PMID- 17440518
TI  - Comparison between omega-3 and omega-6 polyunsaturated fatty acid intakes as
      assessed by a food frequency questionnaire and erythrocyte membrane fatty acid
      composition in young children.
AB  - OBJECTIVE: We conducted a dietary validation study in youth aged 1-11 years by
      comparing dietary intake of omega-3 and omega-6 polyunsaturated fatty acids
      (PUFAs) as assessed by a parent-completed semiquantitative food frequency
      questionnaire (FFQ) over time to erythrocyte membrane composition of the same
      fatty acids. DESIGN: The study population included youth aged 1-11 years who were
      participants in the Diabetes Autoimmunity Study in the Young (DAISY), a
      longitudinal study in Denver, Colorado that is following a cohort of youth at
      risk for developing type I diabetes. Four hundred and four children who had
      erythrocyte membrane fatty acid data matched to an FFQ corresponding to the same
      time frame for a total of 917 visits (matches) were included. PUFA intake was
      expressed both as g/day (adjusted for total energy) and as percent of total fat
      intake. We used mixed models to test the association and calculate the
      correlation between the erythrocyte membrane estimates and PUFA intake using all
      records of data for each youth. RESULTS: Intakes of total omega-3 fatty acids
      (beta=0.52, P<0.0001, rho=0.23) and marine PUFAs (beta=1.62, P<0.0001, rho=0.42),
      as a percent of total fat in the diet, were associated with percent of omega-3
      and marine PUFAs in the erythrocyte membrane. Intakes of omega-6 PUFAs
      (beta=0.04, P=0.418, rho=0.05) and arachidonic acid (beta=0.31, P=0.774,
      rho=0.01) were not associated. CONCLUSIONS: In these young children, an FFQ using
      parental report provided estimates of average long-term intakes of marine PUFAs
      that correlated well with their erythrocyte cell membrane fatty acid status.

PMID- 17440519
TI  - Components of the Mediterranean-type food pattern and serum inflammatory markers
      among patients at high risk for cardiovascular disease.
AB  - OBJECTIVE: To evaluate associations between components of the Mediterranean diet
      and circulating markers of inflammation in a large cohort of asymptomatic
      subjects at high risk for cardiovascular disease. SUBJECTS/METHODS: A total of
      339 men and 433 women aged between 55 and 80 years at high cardiovascular risk
      because of presence of diabetes or at least three classical cardiovascular risk
      factors, food consumption was determined by a semi-quantitative food frequency
      questionnaire. Serum concentrations of high-sensitivity C-reactive protein (CRP)
      were measured by immunonephelometry and those of interleukin-6 (IL-6),
      intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1
      (VCAM-1) by enzyme-linked immunosorbent assay. RESULTS: After adjusting for age,
      gender, body mass index, diabetes, smoking, use of statins, non-steroidal
      antiinflammatory drugs and aspirin, a higher consumption of fruits and cereals
      was associated with lower concentrations of IL-6 (P for trend 0.005;both).
      Subjects with the highest consumption of nuts and virgin olive oil showed the
      lowest concentrations of VCAM-1, ICAM-1, IL-6 and CRP; albeit only for ICAM-1 was
      this difference statistically significant in the case of nuts (for trend 0.003)
      and for VCAM-1 in the case of virgin olive oil (P for trend 0.02). Participants
      with higher adherence to the Mediterranean-type diet did not show significantly
      lower concentrations of inflammatory markers (P<0.1 for VCAM-1 and ICAM-1).
      CONCLUSIONS: The consumption of some typical Mediterranean foods (fruits,
      cereals, virgin olive oil and nuts) was associated with lower serum
      concentrations of inflammatory markers especially those related to endothelial
      function, in subjects with high cardiovascular risk living in a Mediterranean
      country.

PMID- 17440520
TI  - Lactobacillus acidophilus 74-2 and Bifidobacterium animalis subsp lactis DGCC 420
      modulate unspecific cellular immune response in healthy adults.
AB  - OBJECTIVE: It was determined whether a combination of Lactobacillus acidophilus
      (L. acidophilus) 74-2 and Bifidobacterium animalis subsp lactis DGCC 420 (B.
      lactis 420) affect the faecal microbiota as well as immunological parameters and
      blood lipids in healthy adults. DESIGN: A placebo-controlled, double-blinded,
      randomized crossover trial was conducted. SUBJECTS: Twenty-six healthy volunteers
      (mean age 25 years) were recruited by advertising in academical buildings. All of
      them completed the study. METHODS: After 3-week run-in period, half of the
      volunteers consumed 300 g/day of yoghurt supplement containing probiotic strains
      L. acidophilus 74-2 and B. lactis 420, and the other half received the placebo
      product for a period of 5 weeks. The two groups were crossed during the following
      5-week period. Blood and faecal samples were collected at the end of each period.
      The faecal content of probiotic bacteria, faecal short-chain fatty acids (SCFA),
      serum lipids and plasma immune system biomarkers were evaluated. RESULTS: Faecal
      proportions of L. acidophilus and of B. lactis increased significantly from 0.02
      to 0.19 and 0.4 to 1.4% (P<0.05), respectively. Percentages of granulocytes and
      monocytes showing phagocytic activity were significantly elevated from 92 to 95%
      during probiotic intervention, whereas their oxidative burst activity and
      specific immune parameters remained unaffected. Fecal SCFA and serum cholesterol
      levels were not influenced by the probiotics. However, serum concentrations of
      triacylglyceroles decreased significantly by 11.6% (P<0.05) in the probiotic
      supplementation period. CONCLUSIONS: L. acidophilus and B. lactis were recovered
      in faeces in significantly elevated numbers after supplementation. They are able
      to modulate unspecific cellular immune response indicated by the increased
      phagocytic activity.

PMID- 17440521
TI  - Psychometric properties of a modified US-household food security survey module in
      Campinas, Brazil.
AB  - OBJECTIVE: To assess the internal validity of a multiple-item measure of
      household food security in Brazil using statistical methods based on the single
      parameter logistic (Rasch) measurement model. SUBJECTS/METHODS: Sample of the non
      institutionalized civilian population living in the municipality of Campinas
      selected using stratified cluster sampling. Of the 1000 households randomly
      chosen, 847 responded to the interview. Responses to each of the 15 questions
      were coded into dichotomous items indicating whether the specific food-insecure
      condition had occurred (other than in just 1 or 2 days) during the 3 months
      before the survey. Scaling analyses were conducted separately as well as jointly
      for adult/household-related items and child-related items. Item-fit statistics
      were examined to determine the extent to which the items appear to measure the
      same underlying phenomenon, and item severity scores were compared with those of
      equivalent items in the US Current Population Survey. CONCLUSIONS: Except for one
      item, infit statistics were within a range considered adequate (0.80-1.2),
      indicating a common phenomenon being measured with approximately equal
      discrimination. The relative severities of the items in the Campinas survey were
      generally similar to those of equivalent items in the US Current Population
      Survey. Analysis of all 15 items together indicates a higher severity level for
      child-related items compared with equivalent adult-related items.

PMID- 17440522
TI  - Influence of the glycaemic index of an evening meal on substrate oxidation
      following breakfast and during exercise the next day in healthy women.
AB  - OBJECTIVE: To investigate whether the 'overnight second-meal effect' results in
      altered substrate oxidation during the postprandial period following breakfast
      and subsequent sub-maximal exercise in women. SUBJECTS/METHODS: Seven
      recreationally active women were recruited for the study. In each trial,
      participants were provided with their evening meal on day 1, which was composed
      of either high glycaemic index (HGI) or low glycaemic index (LGI) carbohydrates
      (CHO). On day 2, participants were provided with a standard HGI breakfast and
      then performed a 60 min run at 65% ?[V.]O(2 max) 3 h later. RESULTS: The
      incremental area under the curve (IAUC) for plasma glucose concentrations during
      the postprandial period following breakfast was greater in the HGI trial compared
      to the LGI trial (P<0.01). Similarly, the IAUC for serum insulin concentrations
      was greater in the HGI trial than the LGI trial (P<0.05). No differences in
      plasma free-fatty acids (FFA) or plasma glycerol concentrations were found
      between trials during the postprandial period. During subsequent exercise, there
      were no significant differences in substrate metabolism. CONCLUSION: The
      glycaemic index of an evening meal does not alter substrate oxidation at rest
      following breakfast or during subsequent submaximal exercise in women. This study
      provides further evidence for the overnight second-meal effect on glycaemic
      responses following a LGI mixed evening meal.

PMID- 17440523
TI  - Accuracy in the estimation of food servings against the portions in food
      photographs.
AB  - OBJECTIVE: In diet surveys, quantitative underestimation of food consumption may
      be due to intentional misreporting or false portion-size reporting. Perception of
      food photographs used as aids for assessing the actual amounts may have an
      effect. This study was carried out to assess the validity of food photographs.
      DESIGN: A real-time test protocol where 52 presented food servings were compared
      against photographed portions with similar food items. SUBJECTS: Volunteers from
      the Rehabilitation Company Petrea (in Turku) were recruited, 161 adults
      participated, and for 146 subjects, complete data were collected. METHODS: The
      proportions of correct estimations and reporting errors, in weights and
      percentages, are presented by gender and food group. Food descriptors, portion
      size options and subject characteristics were studied as potential determinants
      of accuracy in portion-size estimation. RESULTS: The total proportion of exactly
      correct estimations was 51% in men and 49% in women. The overall reporting error
      was -10 g in men and +1 g in women for the 52 food servings. Underreporting was
      typical for bread, spread and cold cuts and dishes in both genders. Over
      reporting was typical for cereals in both genders and for snacks, vegetables and
      fruit in women. The estimation error was associated with the portion-size options
      but not associated with the energy density of food items, education or body mass
      index. CONCLUSIONS: Food portions in photographs seem to be a useful aid for the
      quantification of most food items. However, validation studies are needed to test
      the applicability of photographs for estimating current portions and for
      searching better tools in dietary surveys.

PMID- 17440524
TI  - Factors associated with adolescents' overweight and obesity at community, school
      and household levels in Xi'an City, China: results of hierarchical analysis.
AB  - OBJECTIVE: To identify personal and environmental factors associated with
      adolescent overweight and obesity in Xi'an city, China. SUBJECTS/METHODS: A total
      of 1804 adolescents from 30 junior high schools in six districts in Xi'an City.
      Community, school, household and individual characteristics were self reported by
      parents, school doctors and students. Factors associated with adolescent
      overweight and obesity were identified using a hierarchical logistic regression.
      RESULTS: In all adolescents, after adjustment for age and gender, factors
      significantly associated with overweight and obesity were: living in urban
      districts (odds ratio (OR): 4.0, 95% confidence interval (CI): 2.7-6.0); limited
      use of school sports facilities (OR: 1.7, 95% CI: 1.1-2.6); wealthy households
      (OR: 1.7, 95% CI: 1.1-2.6); parental restrictions on purchasing snacks (OR: 1.5,
      95% CI: 1.03-2.0); having an overweight/obese parent (OR: 1.8, 95% CI: 1.3-2.5);
      having soft drinks more than four times per week (OR: 1.6, 95% CI: 1.02-2.5) and
      not fussy about foods (OR: 1.7, 95% CI: 1.2-2.2). Eating sweets was negatively
      associated with overweight/obesity (OR: 0.6, 95% CI: 0.4-0.9). Separate gender
      analyses revealed that in boys, low physical activity (OR: 2.0, 95% CI: 1.1-3.8)
      and higher energy intake (OR: 1.8, 95% CI: 1.1-2.9) were also associated with
      overweight/obesity. In girls, less school sports meetings (OR: 2.3, 95% CI: 1.3
      4.0); parental decisions about eating fast foods (OR: 1.8, 95% CI: 1.1-2.9) and
      availability of home video games (OR: 1.7, 95% CI: 1.1-2.5) were also
      significant. CONCLUSIONS: Preventive strategies for adolescent overweight and
      obesity in Xi'an should address the community and school environments to
      reinforce behavioral change. Gender differences also need to be considered when
      planning interventions.

PMID- 17440525
TI  - Effects of products made from a high-palmitic acid, trans-free semiliquid fat or
      a high-oleic acid, low-trans semiliquid fat on the serum lipoprotein profile and
      on C-reactive protein concentrations in humans.
AB  - BACKGROUND: Many studies have shown that trans fatty acids have unfavorable
      effects on the serum lipoprotein profile. In general, however, fats were compared
      with different functional characteristics, which lower the practical applications
      of the results. OBJECTIVE: The major aim of this study was to compare the effects
      of a high-palmitic acid, trans-free semiliquid fat with those of a high-oleic
      acid, low-trans semiliquid fat on the serum lipoprotein profile of healthy
      subjects. SUBJECTS AND DESIGN: Forty-four subjects (33 women and 11 men)
      consumed, in random order, two experimental diets, each for 3 weeks. Diets
      provided 40 energy percent (En%) from fat, while 15 En% was supplied by the
      experimental fats. At the end of each intervention period, concentrations of
      serum lipoproteins, C-reactive protein, glucose and insulin were measured.
      RESULTS: When subjects consumed the high-oleic acid, low-trans semiliquid fat,
      intakes of stearic acid (+1.3 En%), oleic acid (+2.9 En%), alpha-linolenic acid
      (+0.1 En%) and trans fatty acids (+0.6 En%) were higher and that of palmitic acid
      (-4.2 En%) lower. Serum concentration of low-density lipoprotein cholesterol
      decreased by 0.34+/-0.39 mmol/l (mean+/-s.d.; 95% confidence interval (CI), -0.46
      to -0.23 mmol/l; P<0.001) and high-density lipoprotein (HDL) cholesterol by 
      0.06+/-0.17 mmol/l (95% CI, -0.11 to -0.01 mmol/l; P=0.021). Also, the total to
      HDL cholesterol ratio was lower (-0.15+/-0.34; 95% CI, -0.25 to -0.05; P=0.006).
      Other parameters did not change. CONCLUSIONS: A high-oleic acid, low-trans
      semiliquid fat has a more favorable effect on the serum lipoprotein profile than
      a trans-free semiliquid fat with comparable functional characteristics, but high
      in palmitic acid.

PMID- 17440526
TI  - A double-blind, randomized, controlled crossover trial of glutamine
      supplementation in home parenteral nutrition.
AB  - OBJECTIVE: Studies suggest clinical benefit of glutamine-supplemented parenteral
      nutrition. The aim was to determine if the inclusion of 10 g of glutamine as part
      of the nitrogen source of home parenteral nutrition (HPN) reduces infectious
      complications. SUBJECTS/METHODS: Thirty-five patients on HPN were recruited and
      22 completed the study. Patients were randomized to receive either standard HPN
      or glutamine-supplemented HPN. Patients were assessed at randomization, 3 and 6
      months later then they were crossed over to the alternative HPN and reassessed at
      3 and 6 months. Assessments included plasma amino acid concentrations, intestinal
      permeability and absorption, nutritional status, oral and parenteral intake,
      quality of life, routine biochemistry and haematology. RESULTS: No difference was
      seen between the groups at randomization. No difference was detected between the
      treatment phases for infective complications (55% in the standard treatment phase
      and 36% in the glutamine-supplemented phase P=0.67). There were no differences in
      nutritional status, intestinal permeability, plasma glutamine concentrations or
      quality of life. CONCLUSION: Although limited by the sample size, the study has
      shown that glutamine as part of the nitrogen source of parenteral nutrition can
      be given to patients on HPN for 6 months without any adverse effects.

PMID- 17440527
TI  - Pakistani immigrant children and adults in Denmark have severely low vitamin D
      status.
AB  - OBJECTIVE: To determine vitamin D and bone status in adolescent girls, pre
      menopausal women and men of Pakistani origin, to single out determinants of
      vitamin D status and to determine the association between vitamin D status, bone
      metabolism and bone status. SUBJECTS/METHODS: Cross-sectional study, Copenhagen
      (55 degrees N), January-November. Serum 25-hydroxyvitamin D (S-25OHD), serum
      intact parathyroid hormone (S-iPTH), bone turnover markers and whole body and
      lumbar spine bone mineral density were measured. Sun, smoking and clothing
      habits, age, body mass index (BMI), and vitamin D and calcium from food and from
      supplements were recorded. Thirty-seven girls (median age, range: 12.2 years,
      10.1-14.7), 115 women (36.2 years, 18.1-52.7) and 95 men (38.3 years, 17.9-63.5)
      of Pakistani origin (immigrants or descendants with Pakistani parents) took part
      in the study. RESULTS: Median concentration of S-25OHD was 10.9, 12.0 and 20.7
      nmol/l for girls, women and men, respectively. Forty-seven per cent of the girls,
      37% of the women and 24% of the men had elevated S-iPTH, and there was a negative
      relationship between S-iPTH and S-25OHD. Use of vitamin D-containing supplements
      had a positive association with S-25OHD for men (P=0.04) and women (P=0.0008).
      Twenty-one per cent of the women and 34% of the men had osteopenia. Neither S
      25OHD nor S-iPTH was associated with lumbar spine or whole body bone mineral
      content. CONCLUSIONS: Severely low vitamin D status and elevated S-iPTH is common
      among Pakistani immigrants in Denmark. The low vitamin D status is not associated
      with bone markers or bone mass among relatively young Pakistanis.

PMID- 17440528
TI  - Basal plasma concentrations of plant sterols can predict LDL-C response to
      sitosterol in patients with familial hypercholesterolemia.
AB  - BACKGROUND: Familial hypercholesterolemia (FH) is associated with a high risk of
      coronary heart disease. Pharmacological treatment and diet are both essential for
      the management of FH. Foods rich in plant sterols (PS) may play an important role
      in the treatment of patients with these disorders. OBJECTIVE: To test the effect
      of the intake of PS on low-density lipoprotein (LDL) concentration, endothelial
      function (EF) and LDL particle size in 30 patients with FH. DESIGN: Randomized
      and crossover dietary intervention study. SETTING: Tertiary outpatient care.
      SUBJECTS: Thirty-eight were recruited, but only 30 were subjected to four low-fat
      dietary intervention periods, each of 4 weeks. METHODS: Each intervention had a
      different content of cholesterol (<150 or 300 mg/day) and sitosterol (<1 or 2
      g/day). Lipid response, EF and LDL particle size were analysed after the
      intervention. RESULTS: Plasma sitosterol/cholesterol ratio was higher during both
      plant sterol-rich periods than during the low plant sterols periods. Basal
      sitosterol concentrations predicted the LDL-cholesterol response during the
      intake of plant sterol-enriched diets. The change in LDL-cholesterol was
      significantly greater in subjects in the upper and intermediate tertiles of basal
      plasma sitosterol concentrations (-21+/-8 mg/dl, P=0.03; -19+/-7 mg/dl, P=0.04,
      respectively) than in subjects in the lower tertile (8+/-5 mg/dl) when they
      changed from a low cholesterol diet to a low cholesterol plus plant sterol diet.
      CONCLUSION: Our study demonstrates that basal sitosterol values can predict
      hypolipidemic response in patients with FH.

PMID- 17440529
TI  - Oxalic acid does not influence nonhaem iron absorption in humans: a comparison of
      kale and spinach meals.
AB  - OBJECTIVE: To evaluate the influence of oxalic acid (OA) on nonhaem iron
      absorption in humans. DESIGN: Two randomized crossover stable iron isotope
      absorption studies. SETTING: Zurich, Switzerland. SUBJECTS: Sixteen apparently
      healthy women (18-45 years, <60 kg body weight), recruited by poster advertizing
      from the staff and student populations of the ETH, University and University
      Hospital of Zurich, Switzerland. Thirteen subjects completed both studies.
      METHODS: Iron absorption was measured based on erythrocyte incorporation of
      (57)Fe or (58)Fe 14 days after the administration of labelled meals. In study I,
      test meals consisted of two wheat bread rolls (100 g) and either 150 g spinach
      with a native OA content of 1.27 g (reference meal) or 150 g kale with a native
      OA content of 0.01 g. In study II, 150 g kale given with a potassium oxalate
      drink to obtain a total OA content of 1.27 g was compared to the spinach meal.
      RESULTS: After normalization for the spinach reference meal absorption, geometric
      mean iron absorption from wheat bread rolls with kale (10.7%) did not differ
      significantly from wheat rolls with kale plus 1.26 g OA added as potassium
      oxalate (11.5%, P=0.86). Spinach was significantly higher in calcium and
      polyphenols than kale and absorption from the spinach meal was 24% lower compared
      to the kale meal without added OA, but the difference did not reach statistical
      significance (P>0.16). CONCLUSION: Potassium oxalate did not influence iron
      absorption in humans from a kale meal and our findings strongly suggest that OA
      in fruits and vegetables is of minor relevance in iron nutrition.

PMID- 17440530
TI  - Biology by numbers: mathematical modelling in developmental biology.
AB  - In recent years, mathematical modelling of developmental processes has earned new
      respect. Not only have mathematical models been used to validate hypotheses made
      from experimental data, but designing and testing these models has led to
      testable experimental predictions. There are now impressive cases in which
      mathematical models have provided fresh insight into biological systems, by
      suggesting, for example, how connections between local interactions among system
      components relate to their wider biological effects. By examining three
      developmental processes and corresponding mathematical models, this Review
      addresses the potential of mathematical modelling to help understand development.

PMID- 17440531
TI  - Genetic determinants of cancer metastasis.
AB  - Metastasis can be viewed as an evolutionary process, culminating in the
      prevalence of rare tumour cells that overcame stringent physiological barriers as
      they separated from their original environment and developmental fate. This
      phenomenon brings into focus long-standing questions about the stage at which
      cancer cells acquire metastatic abilities, the relationship of metastatic cells
      to their tumour of origin, the basis for metastatic tissue tropism, the nature of
      metastasis predisposition factors and, importantly, the identity of genes that
      mediate these processes. With knowledge cemented in decades of research into
      tumour-initiating events, current experimental and conceptual models are
      beginning to address the genetic basis for cancer colonization of distant organs.

PMID- 17440532
TI  - Animal models of human disease: zebrafish swim into view.
AB  - Despite the pre-eminence of the mouse in modelling human disease, several aspects
      of murine biology limit its routine use in large-scale genetic and therapeutic
      screening. Many researchers who are interested in an embryologically and
      genetically tractable disease model have now turned to zebrafish. Zebrafish
      biology allows ready access to all developmental stages, and the optical clarity
      of embryos and larvae allow real-time imaging of developing pathologies.
      Sophisticated mutagenesis and screening strategies on a large scale, and with an
      economy that is not possible in other vertebrate systems, have generated
      zebrafish models of a wide variety of human diseases. This Review surveys the
      achievements and potential of zebrafish for modelling human diseases and for drug
      discovery and development.

PMID- 17440533
TI  - High-peak-power femtosecond pulse compression with polarization-maintaining
      ytterbium-doped fiber amplification.
AB  - We report the generation of 140 fs pulses with a peak power of up to 270 kW using
      a fiber pulse source based on a polarization-maintaining ytterbium-doped fiber
      amplifier and a semiconductor saturable absorber mirror mode-locked fiber laser
      seed. The seed laser pulses were amplified and chirped in the fiber amplifier and
      subsequently compressed in an external transmission grating pair. The use of a
      polarization-maintaining amplifier addresses nonlinear polarization-induced
      limitations to the obtainable compressed pulse duration and quality that can
      arise if isotropic fiber amplification is used. Numerical simulations of the
      system support the experimental measurements and also confirm the role of fiber
      dispersion in obtaining high-quality compressed pulses.

PMID- 17440534
TI  - Effect of polymer coating on leakage losses in Bragg fibers.
AB  - It is found that the reflection of leaky radiation from the interface between the
      outer silica cladding and the coating polymer greatly modifies the loss spectrum
      of Bragg fibers. A simple model that describes this effect is proposed and
      confirmed by measurement and computation.

PMID- 17440535
TI  - Transmission of Cerenkoverenkov radiation in optical fibers.
AB  - Cerenkov radiation is generated as an unwanted background when optical fibers
      carrying signals pass through radiation fields. The angular dependence of the
      intensity of ? Cerenkov radiation transmitted in silica-core fibers was measured
      using 6 and 12 MeV electron beams from a Varian Clinic accelerator. These
      confirmed theoretical predictions that the angular variation of ? Cerenkov
      radiation transmitted along optical fibers depends only on the refractive index
      difference Dn between the core and the cladding, and that the peak intensity is
      proportional to the cube of the fiber core radius.

PMID- 17440536
TI  - Highly dispersive large mode area photonic bandgap fiber.
AB  - An all-silica photonic bandgap fiber composed of a low-index core surrounded by
      alternating high- and low-index rings allows us to achieve a large mode area (500
      microm(2)) and large chromatic dispersion. Sharp resonances from the even Bragg
      mode to odd ring modes theoretically lead to 20,000 ps/(nm km) chromatic
      dispersion when large bends are applied. By nature, sharp resonances are
      sensitive to inhomogeneities along the fiber length. Under experimental
      conditions, the resonances are broadened and the dispersion coefficient is
      decreased to 1000 ps/(nm km). However, to the best of our knowledge, this is the
      largest dispersion coefficient reported using a large mode area fiber.

PMID- 17440537
TI  - Optical AND gate based on soliton interaction in a fiber Bragg grating.
AB  - Using computer simulations, we demonstrate an optical cascadable AND gate based
      on soliton interaction in a fiber Bragg grating. A single soliton that is
      launched into the device is backreflected. When two solitons are launched, one of
      the solitons is transmitted while the other is backreflected. The time delay
      between the solitons may be few times longer than the duration of the solitons.
      We show that the interaction causes an increase in the frequency of one of the
      solitons that enables its transmission through the grating bandgap.

PMID- 17440538
TI  - Bandwidth-tunable band-rejection filter based on helicoidal fiber grating pair of
      opposite helicities.
AB  - We have developed a new type of all-fiber band-rejection filter consisting of a
      helicoidal long-period fiber grating pair of opposite helicities, which provides
      highly flexible spectral control over the rejection bandwidth. The detailed
      fabrication method and operation principles of the proposed bandwidth-tunable
      band-rejection filter are described. The proposed device enables unique rejection
      bandwidth tuning over more than 14 nm at the rejection level of 15 dB, with low
      insertion loss and polarization-dependent loss achieved by adjusting torsion
      stress.

PMID- 17440539
TI  - Convergence of phase fluctuation induced by intrachannel four-wave mixing in
      differential phase-shift keying transmission systems via phase fluctuation
      averaging.
AB  - This work investigates the effect of phase fluctuation averaging on phase
      fluctuation induced by intrachannel four-wave mixing (IFWM) in highly dispersed
      differential phase-shift keying transmission systems. Through repeatedly
      averaging the phase fluctuations of adjacent pulses, a simple analytical model
      and numerical simulation revealed that the IFWM-induced differential phase
      fluctuation is suppressed and convergent, even after an ultralong transmission.
      The influence of averaging the phase fluctuations on the bit error rate is also
      evaluated by the semianalytical method.

PMID- 17440540
TI  - Wide viewing angle skewed effect of the point spread function in a wavefront
      coding system.
AB  - The point spread function (PSF) of a wavefront coding (WFC) system with a cubic
      phase mask is analyzed with a wide viewing angle based on physical optics for
      what is believed to be the first time. Two coordinate transformations are made to
      generate a pupil function, from which we obtain the encoded PSF of the WFC system
      with defocus parameters W(020) and object angles alpha and beta. The encoded PSFs
      are further side extended as the object angles get wider. When alphabeta<0, the
      included angle ? of encoded PSF will skew to an obtuse angle. When alphabeta=0, ?
      remains orthogonal; when alphabeta>0, ? will skew to an acute angle. Furthermore,
      the effect of skew and side extension is even symmetric about W(020). As a
      result, the wide viewing angle has a bad effect on the imaging quality of the WFC
      system.

PMID- 17440541
TI  - Ultrawideband monocycle generation using cross-phase modulation in a
      semiconductor optical amplifier.
AB  - We propose a novel scheme to generate ultrawideband (UWB) monocycle pulses based
      on cross-phase modulation (XPM) of a semiconductor optical amplifier (SOA). The
      proposed system consists of a SOA and an optical bandpass filter (OBF). Due to
      the XPM, a continuous wave (CW) probe signal is phase modulated by another
      optical Gauss pulse in the SOA. The OBF will convert the phase modulation to
      intensity modulation. A pair of polarity-reversed UWB monocycle pulses is
      achieved by locating the probe carrier at the positive and negative linear slopes
      of the OBF. Both cases conform to the UWB definition of the Federal
      Communications Commission.

PMID- 17440542
TI  - Orthonormal mode sets for the two-dimensional fractional Fourier transformation.
AB  - A family of orthonormal mode sets arises when Hermite-Gauss modes propagate
      through lossless first-order optical systems. It is shown that the modes at the
      output of the system are eigenfunctions for the symmetric fractional Fourier
      transformation if and only if the system is described by an orthosymplectic ray
      transformation matrix. Essentially new orthonormal mode sets can be obtained by
      letting helical Laguerre-Gauss modes propagate through an antisymmetric
      fractional Fourier transformer. The properties of these modes and their
      representation on the orbital Poincare sphere are studied.

PMID- 17440543
TI  - Depth-independent segmentation of macroscopic three-dimensional objects encoded
      in single perspectives of digital holograms.
AB  - We present a technique for performing segmentation of macroscopic three
      dimensional objects recorded using in-line digital holography. We numerically
      reconstruct a single perspective of each object at a range of depths. At each
      point in the digital wavefront we calculate variance about a neighborhood. The
      maximum variance at each point over all depths is thresholded to classify it as
      an object pixel or a background pixel. Segmentation results for objects of low
      and high contrast are presented.

PMID- 17440544
TI  - Denoising in digital speckle pattern interferometry using wave atoms.
AB  - We present an effective method for speckle noise removal in digital speckle
      pattern interferometry, which is based on a wave-atom thresholding technique.
      Wave atoms are a variant of 2D wavelet packets with a parabolic scaling relation
      and improve the sparse representation of fringe patterns when compared with
      traditional expansions. The performance of the denoising method is analyzed by
      using computer-simulated fringes, and the results are compared with those
      produced by wavelet and curvelet thresholding techniques. An application of the
      proposed method to reduce speckle noise in experimental data is also presented.

PMID- 17440545
TI  - Surface plasmon interferometry: measuring group velocity of surface plasmons.
AB  - Optical transmission spectroscopy on metal films with slit-groove pairs is
      conducted. Spectra of the light transmitted through the slit exhibit Fabry-Perot
      type interference fringes due to surface plasmons propagating between the slit
      and the groove. The spectral dependence of the period of interference fringes is
      used to determine the group velocity of surface plasmons on flat gold and silver
      surfaces.

PMID- 17440546
TI  - Quantitative two-dimensional shadowgraphic method for high-sensitivity density
      measurement of under-critical laser plasmas.
AB  - We present a quantitative shadowgraphic method that can measure the density of a
      laser-generated plasma in air. Simultaneous comparison of both shadowgraphy and
      interferometry has been carried out, allowing the experimental evaluation of the
      reliability of the shadowgraphic method. Even though limited by absorption in the
      sample, shadowgraphy performs better in terms of sensitivity.

PMID- 17440547
TI  - Mode-locked laser-type optical atomic clock with an optically pumped Cs gas cell.
AB  - We propose and demonstrate a mode-locked laser-type optical atomic clock with an
      optically pumped cesium (Cs) gas cell. By adopting the optically pumped Cs gas
      cell with a double resonance method as a frequency standard, we have successfully
      demonstrated an ultrastable rack-mount type Cs optical atomic clock with
      excellent short-term stability. The obtained frequency stabilities reached as
      high as 1.2 x 10(-12) for tau=1 s and 8.8 x 10(-14) for tau=100 s for a 9.1926
      GHz microwave output signal.

PMID- 17440548
TI  - High-contrast coherent population trapping resonances using four-wave mixing in
      87Rb.
AB  - We demonstrate very high-contrast coherent population trapping(1) (CPT)
      resonances by using four-wave mixing in (87)Rb atoms. In the experiment, we take
      advantage of the spectral overlap between F=2-->F(?) and F=3-->F(?) optical
      resonances on the D1 line of (87)Rb and (85)Rb atoms, respectively, to eliminate
      the DC-light background from the CPT resonance signal. We observe a CPT resonance
      with a contrast in the range of 90%, compared with a few percent achieved by
      alternative methods.

PMID- 17440549
TI  - Low-coherence self-referencing velocimetry.
AB  - Low-coherence self-referencing velocimetry optically measures the relative
      velocity between a point in a particle-laden fluid and a (potentially moving)
      reference surface. Low-coherence light scattered off the particles and off the
      reference surface is coupled into an interferometer with variable optical delay
      in one arm and an acousto-optical modulator in the second arm. The measurement
      location is set relative to the reference surface. Its location can be scanned
      along a line by adjusting the optical delay in the interferometer. The spatial
      resolution is typically tens of micrometers. Only one low-coherence light beam is
      required for each component of the velocity vector. Proof-of-principle
      measurements in Taylor-Couette flow are presented.

PMID- 17440550
TI  - Lossless strip-to-slot waveguide transformer.
AB  - We present a highly efficient integratable waveguide transformer that is capable
      of converting Gaussian-like waveguide modes to much more complicated non-Gaussian
      like slot-waveguide modes, and vice versa. The structure consists of several
      pairs of complementary tapers capable of making this mode conversion virtually
      lossless. The capability of extremely low-loss mode transformation between these
      two classes of waveguides has been demonstrated by means of single- and double
      slot transformers. Our simulation has shown that the total transformation losses
      are less than 0.01 and 0.02 dB per transformer, respectively, and can be easily
      achieved, with a total device length of less than 100 microm.

PMID- 17440551
TI  - Add-drop filters based on mode-conversion cavities.
AB  - A new type of a resonator defined by two or more mode-converting gratings in a
      waveguide is proposed and analyzed. It is shown that the proposed structure can
      exhibit narrow resonances similar to Fabry-Perot cavities but has an advantage of
      being a four-port device and thus is capable of serving as an add-drop filter.

PMID- 17440552
TI  - Electrically pumped edge-emitting photonic crystal lasers with angled facets.
AB  - We demonstrate electrically pumped large-area edge-emitting InGaAsP/InP two
      dimensional photonic crystal lasers with angled facets at room temperature. The
      laser uses a weak index perturbation surface photonic crystal structure to
      control optical modes in the wafer plane. Measurements of the laser spectra show
      that the modal selection is due to satisfying the Bragg resonance conditions in
      both the longitudinal and the transverse directions. The lasing wavelength is
      tuned lithographically by changing photonic crystal lattice constants. We
      demonstrate a fine lasing wavelength tuning sensitivity (change of lasing
      wavelength over change of lattice constant) of 0.08 through the transverse
      lattice constant tuning.

PMID- 17440553
TI  - 111 W, 110 MHz repetition-rate, passively mode-locked TEM00Nd:YVO4 master
      oscillator power amplifier pumped at 888 nm.
AB  - We report on an 888 nm pumped passively mode-locked TEM(00)Nd:YVO(4) oscillator
      providing 56 W of average power at a repetition rate of 110 MHz with 33 ps pulse
      duration, further amplified to 111 W in a 52% optical efficiency single-pass
      amplifier stage, maintaining beam quality at M(2)=1.05. Frequency doubling in a
      LiB(3)O(5) crystal generated up to 87 W at 532 nm, while a third harmonic power
      of 35 W was achieved in a nonoptimized tripling configuration, corresponding to
      80% and 33% conversion efficiency.

PMID- 17440554
TI  - Monolithic Nd:YVO4 slab oscillator-amplifier.
AB  - We report on a compact, efficient, and reliable monolithic Nd:YVO(4) slab
      oscillator-amplifier with an output power of 29.3 W in cw operation and an
      optical-to-optical efficiency of 24%. In electro-optically Q-switched operation,
      28.8 W of average power at a repetition rate of 100 kHz with a pulse width of 15
      ns was measured. The RMS stability of the pulse energy is better than 1.7%. The
      beam quality M(2) in both cw and pulse models was under 1.3.

PMID- 17440555
TI  - Resonant frequency-domain interferometry via third-harmonic generation.
AB  - A method for measuring resonances using a combination of third-harmonic
      generation and frequency-domain interferometry is described and demonstrated in
      an index-matched dielectric material. The phase of the third-harmonic spectrum of
      a pulse generated from a resonant NdAlO(3) thin film and a temporally displaced
      sapphire substrate pulse was measured by analyzing the spectral interference
      pattern. The appropriate combination of substrate and film signals was obtained
      by translating the sample through the laser focus while observing the third
      harmonic intensity.

PMID- 17440556
TI  - Long-cavity quantum dot laser.
AB  - We propose a delay-differential equation to model dynamical instabilities in a
      quantum dot laser. We focus on a laser with a small gain section and a long empty
      section. A long cavity reduces the strong damping of the relaxation oscillation
      frequency. It leads to the appearance of dropouts at the delay period, which
      evolve to chaos.

PMID- 17440558
TI  - Diode-pumped efficient slab laser with two Nd:YLF crystals and second-harmonic
      generation by slab LBO.
AB  - We demonstrate a diode-pumped electro-optical Q-switched slab laser with a high
      optical efficiency, high pulse energy, and short pulse width with two Nd:YLF
      crystals inside one resonator. The single compact slab resonator can generate a
      1D top-hat beam at both the far field and the near field. With a slab-geometry
      design lithium triborate (LBO) crystal, efficient critical phase-matching second
      harmonic generation for a 1D top-hat beam with multiple transverse modes is
      achieved.

PMID- 17440559
TI  - Controlled rotational Raman echo recurrences and modulation of high-intensity
      ultrashort laser pulses by molecular rotations in the gas phase.
AB  - We show that sequences of femtosecond laser pulses can control the rotational
      Raman response of a gas mixture, giving rise to a tunable manifold of echo
      recurrences in the retarded nonlinear-optical response of the gas. Tailored phase
      masks for high-intensity ultrashort laser pulses are experimentally demonstrated
      using molecular rotations in the gas phase driven by optimally time-ordered pulse
      sequences.

PMID- 17440560
TI  - Absolute radiance imaging using parametric image amplification.
AB  - We show that parametric image amplification can be used to achieve a 2D radiance
      map directly expressed in photons per spatiotemporal mode. Radiance images of
      incoherent signals with less than one photon per mode (typically 10(-2)) are
      resolved.

PMID- 17440561
TI  - Spectral broadening and stimulated Raman conversion in a continuous-wave optical
      parametric oscillator.
AB  - We have confirmed that single-frequency oscillation of a continuous-wave singly
      resonant optical parametric oscillator is limited to operation below a critical
      value of the pumping ratio, as predicted by early theoretical treatments. We also
      report different regimes of spectral broadening as well as stimulated Raman
      conversion of the signal wave above this critical pump level. We show that
      spectral broadening may be eliminated by implementing output coupling of the
      signal wave and demonstrate 8.6 W of total signal and idler output with single
      frequency spectra at both wavelengths for 14.5 W of pump power.

PMID- 17440562
TI  - Intracavity terahertz-wave generation in a synchronously pumped optical
      parametric oscillator using quasi-phase-matched GaAs.
AB  - We generated 1 mW of average output power at 2.8 THz (bandwidth of approximately
      300 GHz) in a diffraction-limited beam by placing a 6-mm-long quasi-phase-matched
      GaAs crystal inside the cavity of a synchronously pumped optical parametric
      oscillator (OPO). The OPO used type-II-phase-matched periodically poled lithium
      niobate as a gain medium and was pumped by a mode-locked laser at 1064 nm, with a
      7 ps pulse duration, 50 MHz repetition rate, and 10 W average output power. The
      terahertz radiation was generated by difference frequency mixing between the
      signal and idler waves of the near-degenerate doubly resonant OPO.

PMID- 17440563
TI  - Suppression of sideband frequency shifts in the modulational instability spectra
      of wave propagation in optical fiber systems.
AB  - In standard optical fibers with constant chromatic dispersion, modulational
      instability (MI) sidebands execute undesirable frequency shifts due to fiber
      losses. By means of a technique based on average-dispersion-decreasing dispersion
      managed fibers, we achieve both complete suppression of the sideband frequency
      shifts and fine control of the MI frequencies, without any compromise in the MI
      power gain.

PMID- 17440564
TI  - Generation of 250 mW narrowband pulsed ultraviolet light by frequency quadrupling
      of an amplified erbium-doped fiber laser.
AB  - We demonstrate a high-power, narrowband pulsed source at 390 nm by two stages of
      frequency doubling in periodically poled MgO:LiNbO(3) and periodically poled
      KTiOPO(4) of an amplified, passively mode-locked fiber laser. With a frequency
      quadrupling efficiency of 5.5% and a 0.1 nm bandwidth, the 250 mW ultraviolet
      source is a suitable compact pump source for many entanglement-based quantum
      information processing tasks.

PMID- 17440565
TI  - Multivortex solitons in triangular photonic lattices.
AB  - We introduce a novel class of stable lattice solitons with a complex phase
      structure composed of many single-charge discrete vortices in a triangular
      photonic lattice. We demonstrate that such nonlinear self-trapped states are
      linked to the resonant Bloch modes, which bear a honeycomb pattern of phase
      dislocations.

PMID- 17440566
TI  - Multiwavelength ultralow-threshold lasing in quantum dot photonic crystal
      microcavities.
AB  - We demonstrate multiwavelength lasing of resonant modes in linear (L3)
      microcavities in a triangular-lattice 2D photonic crystal (PC) slab. The broad
      spontaneous emission spectrum from coupled quantum dots, modified by the PC
      microcavity, is studied as a function of the intensity of incident optical
      excitation. We observe lasing with an ultralow-threshold power of approximately
      600 nW and an output efficiency of approximately 3% at threshold. Two other
      resonant modes exhibit weaker turnon characteristics and thresholds of
      approximately 2.5 and 200 microW, respectively.

PMID- 17440567
TI  - Polarizing beam splitter of a deep-etched fused-silica grating.
AB  - We described a highly efficient polarizing beam splitter (PBS) of a deep-etched
      binary-phase fused-silica grating, where TE- and TM-polarized waves are mainly
      diffracted in the -1st and 0th orders, respectively. To achieve a high extinction
      ratio and diffraction efficiency, the grating depth and period are optimized by
      using rigorous coupled-wave analysis, which can be well explained based on the
      modal method with effective indices of the modes for TE/TM polarization.
      Holographic recording technology and inductively coupled plasma etching are
      employed to fabricate the fused-silica PBS grating. Experimental results of
      diffraction efficiencies approaching 80% for a TE-polarized wave in the -1st
      order and more than 85% for a TM-polarized wave in the 0th order were obtained at
      a wavelength of 1550 nm. Because of its compact structure and simple fabrication
      process, which is suitable for mass reproduction, a deep-etched fused-silica
      grating as a PBS should be a useful device for practical applications.

PMID- 17440568
TI  - Monolithic fluoride-fiber laser at 1480 nm using fiber Bragg gratings.
AB  - We report what we believe is the first monolithic fluoride-fiber laser making use
      of fiber Bragg gratings written directly in the doped fluoride-fiber core. The
      Tm(3+):ZBLAN fiber laser is upconversion pumped at 1070 nm and emits at 1480 nm.
      Using two different all-fiber cavities, we observed a threshold as low as 75 mW
      and a conversion efficiency of up to 40% with respect to launched pump power.

PMID- 17440569
TI  - Acousto-optic polarization-dependent mode coupling in a dual-mode hollow optical
      fiber.
AB  - We demonstrated unique polarization dependence in acousto-optic coupling in a two
      mode hollow optical fiber (HOF). Local deformation of circular HOF induced by
      traveling acoustic wave resulted in highly birefringent optical transmission
      characteristics, which were experimentally analyzed for various central air-hole
      sizes. Potential applications for polarization-dependent devices such as
      polarization-dependent loss compensators and broadband polarization controllers
      are discussed.

PMID- 17440570
TI  - Total internal reflection ellipsometry: ultrahigh sensitivity for protein
      adsorption on metal surfaces.
AB  - Total internal reflection ellipsometry (TIRE) is used to study adsorption of
      human serum albumin and fibrinogen on thin gold films. TIRE shows very high
      sensitivity for protein monolayers adsorbed on metal surfaces when surface
      plasmon resonance effects are utilized. The measured data, expressed in
      ellipsometric angles psi and D are of several orders of magnitude larger in
      comparison with those from similar experiments performed with traditional
      ellipsometry. TIRE in spectral mode opens a new path for precise studies of
      organic layers adsorbed on metal surfaces, with a potential for resolving the
      adsorbed layer microstructure.

PMID- 17440571
TI  - Extraneous self-imaging phenomenon with weak-guiding condition.
AB  - We discuss a self-imaging phenomenon in a multimode interference (MMI) coupler.
      From experiment, different self-images, which are undefined in MMI theory, are
      observed. These undefined self-images are named "extraneous self-images" (Ex_SIs)
      for convenience. To estimate the applicability of the Ex_SIs, the characteristics
      of both the single self-image (0 dB self-image, 0 dB SI), which is defined in MMI
      theory, and the Ex_SI are compared and analyzed through simulation and
      experiment. The results show that the Ex_SI has an imaging period that is the
      same as the 0 dB SI and that the excess loss and the extinction ratio of the
      Ex_SI improve more than that of the 0 dB SI as the imaging period increases.

PMID- 17440572
TI  - Effective optical constants in stratified metal-dielectric metameterial.
AB  - Effective optical constants of stratified metal-dielectric metameterial are
      presented. The effective constants are determined by the two-complex reflectivity
      method (TCRM). The TCRM reveals the full components of the effective permittivity
      and permeability tensors and indicates the remarkable anisotropy of metallic and
      dielectric components below the effective plasma frequency. On the other hand,
      above the plasma frequency, one of the effective refractive indices takes a
      positive value less than unity and is associated with small loss. The photonic
      states are confirmed by the distribution of electromagnetic fields.

PMID- 17440573
TI  - All-optical switching at ultralow light levels.
AB  - We report an experimental demonstration of all-optical switching at ultralow
      light levels in coherently prepared Rb atoms. A signal light pulse is switched on
      and off by a control light pulse at different frequencies in a four-level atomic
      system based on multiphoton interferences. We observed a switching efficiency of
      55% with the signal and control light pulses containing approximately 20 photons
      each, corresponding to a control energy density of approximately 10(-5) photons
      per atomic cross section lambda(2)/(2pi).

PMID- 17440574
TI  - Four-photon interference with asymmetric beam splitters.
AB  - Two experiments of four-photon interference are performed with two pairs of
      photons from parametric downconversion with the help of asymmetric beam
      splitters. The first experiment is a generalization of the Hong-Ou-Mandel
      interference effect to two pairs of photons while the second one utilizes this
      effect to demonstrate a four-photon de Broglie wavelength of lambda/4 by
      projection measurement.

PMID- 17440575
TI  - Electromagnetically induced transparency in Rb-filled coated hollow-core photonic
      crystal fiber.
AB  - We report the observation of lambda-configuration electromagnetically induced
      transparency as well as optical pumping in rubidium-filled kagome-structure
      hollow-coated-core photonic crystal fiber. We show that a polydimethylsiloxane
      coating of the fiber core reduces the linewidth of the transparency below that
      which could be expected for an uncoated fiber. The measured 6 MHz linewidth was
      dominated by optical broadening.

PMID- 17440576
TI  - Application of Mie theory to determine the structure of spheroidal scatterers in
      biological materials.
AB  - We present here the results of a numerical study on light scattering from
      nonspherical particles with relevance to detecting precancerous states in
      epithelial tissues. In previous studies of epithelial cell nuclei, the
      experimental light scattering data have been analyzed by comparison with Mie
      theory. However, given the spheroidal shape of many cell nuclei, the validity of
      this assumption demands a thorough investigation. We investigate this assumption
      by using the T-matrix method to model light scattered from spheroids with
      parameters relevant to epithelial cell nuclei. In our previous studies, we have
      developed a data analysis procedure that extracts the oscillatory component of
      the angular-scattering distribution for an ensemble of epithelial cell nuclei for
      comparison with Mie theory. We demonstrate that application of our analysis
      procedure to the predictions of the T-matrix method for spheroids, oriented such
      that their axis of symmetry is aligned with the incident light propagation
      direction, generally yields the spheroid dimension that is transverse to the
      incident light propagation direction with subwavelength accuracy.

PMID- 17440577
TI  - Use of apodization in quantitative spectroscopy.
AB  - Apodization, which is a tool frequently used for cosmetic representation and
      efficient modeling of a spectrum, is now also adopted in techniques for the
      quantitative retrieval of parameters from observed spectra. Whether apodization
      can help in quantitative spectroscopy is the subject of debate in the literature.
      We find that, when the considered spectral range is wide enough to accurately
      model the instrument line shape, the same results can be obtained with and
      without apodization of the spectrum. However, when a truncation error is
      introduced by the limited extension of the modeled spectral interval, apodization
      can efficiently reduce this error. Therefore it is possible to save computing
      time by using apodization.

PMID- 17440578
TI  - Fourier transform spectral interferometric coherent anti-Stokes Raman scattering
      (FTSI-CARS) spectroscopy.
AB  - A novel Fourier transform spectral interferometric (FTSI) multiplex coherent anti
      Stokes Raman scattering (CARS) technique is developed to extract the vibrational
      spectrum equivalent to the spontaneous Raman scattering. The conventional FTSI
      method is modified to use the internal nonresonant CARS signal as a local
      oscillator to perform spectral interferometry. Utilizing the causality of the
      coherent vibration (i.e., there should be no signal before the laser excitation),
      this new FTSI method recovers the entire complex vibrational spectral parameters.
      We demonstrate this technique with a previously reported single-pulse multiplex
      CARS method that uses a single phase-controlled broadband ultrafast laser pulse.

PMID- 17440579
TI  - n-Type GaAs/AlGaAs heterostructure detector with a 3.2 THz threshold frequency.
AB  - Terahertz detection using the free-carrier absorption requires a small internal
      work function of the order of a few millielectron volts. A threshold frequency of
      3.2 THz (93 microm or approximately 13 meV work function) is demonstrated by
      using a 1 x 10(18) cm(-3) Si-doped GaAs emitter and an undoped Al(0.04)Ga(0.96)As
      barrier structure. The peak responsivity of 6.5 A/W, detectivity of 5.5 x 10(8)
      Jones, and quantum efficiency of 19% were obtained at 7.1 THz under a bias field
      of 0.7 kV/cm at 6 K, while the detector spectral response range spans from 3.2 to
      30 THz.

PMID- 17440580
TI  - Mass-limited Sn target irradiated by dual laser pulses for an extreme ultraviolet
      lithography source.
AB  - A thin Sn film was investigated as a mass-limited target for an extreme
      ultraviolet (EUV) lithography source. It was found that those energetic ions that
      are intrinsic with the mass-limited Sn target could be efficiently mitigated by
      introducing a low-energy prepulse. High in-band conversion efficiency from a
      laser to 13.5 nm EUV light could be obtained using an Sn film with a thickness
      down to 30 nm when irradiated by dual laser pulses. It was shown that the
      combination of dual pulse and inert Ar gas could fully mitigate ions with a low
      ambient pressure nearly without the penalty of the absorption of the EUV light.

PMID- 17440581
TI  - Comment on "Temporally resolved electro-optic effect".
AB  - We comment on the recent Letter by S. P. Jamison et al. [Opt. Lett.31, 1753
      (2006)] where the analysis of a chirped probe pulse that is electro-optically
      modulated by a terahertz pulse reportedly results in a new expression for the
      electric field. While in principle the derived expressions for the total field
      after the crystal are correct, in their treatment the authors implicitly assumed
      that the derived total field is identical to the measured field, without regard
      to the residual birefringence of a typical electro-optic crystal or a crossed
      analyzer. Based on this analysis neglecting birefringence, they report that
      earlier expressions of the temporal field are incorrect. Here we show, on the
      contrary, that for chirped single-shot terahertz measurement schemes that include
      residual birefringence, the temporally resolved electro-optic effect is described
      correctly by the commonly used expression in the literature. We verify this
      result with our experimental data.

PMID- 17440583
TI  - [Genetic epidemiological study on discordant sib pairs of ischemic stroke in
      Beijing Fangshan District].
AB  - OBJECTIVE: To investigate the association among serum lipids, blood pressure, 
      514C/T polymorphism of hepatic lipase gene and subtypes of ischemic stroke in the
      discordant sib pairs. METHODS: Ischemic stroke cases were enrolled from a
      hospital-based stroke registry, the proband-initiated contact was used to recruit
      pedigrees, and participants' information and blood samples were collected through
      the community-based health care networks in rural areas of China. Statistical
      analysis was performed by using the Wilcoxon signed rank test to compare
      quantitative differences between sib pairs and the McNemar test to compare
      qualitative differences. Generalized estimating equation (GEE) was used to adjust
      for within-family correlation in analysis of discordant sib pairs. Family based
      association test (FBAT) was applied to associations between serum lipids, blood
      pressure and the -514T allele in hepatic lipase gene. RESULTS: Totally 107
      discordant sib pairs from 71 ischemic stroke patients pedigrees were analyzed by
      univariate and multivariate methods. The blood pressure and serum lipids were
      associated with ischemic stroke (P<0.05) The lipid level was higher in large
      artery atherosclerosis ischemic stroke than in the subtype of small-vessel
      occlusion, while the blood pressure was higher in the latter. The -514T allele in
      hepatic lipase gene was associated with low density lipoprotein-cholesterol (LDL
      C) and diastolic blood pressure in additive model by FBAT analysis (Z=2.366,
      P<0.05), and it was also associated with diastolic blood pressure in additive
      model (Z=-2.277, P<0.05) and recessive model (Z=-2.244,P< 0.05), but not
      associated with ischemic stroke or its subtypes. CONCLUSION: In these discordant
      sib pairs, the abnormalities of blood pressure and serum lipids may increase
      risks of ischemic stroke, and different subtypes of ischemic stroke may differ
      from each other in etiology. The -514T allele in hepatic lipase gene may be
      associated with LDL-C and diastolic blood pressure.

PMID- 17440584
TI  - [Secular growth trends in the Chinese urban youth and its implications on public
      health].
AB  - OBJECTIVE: To analyze the secular growth trends of the Chinese urban youth from
      1979 to 2005, in order to make national intervention strategies and measures to
      improve their physical fitness and health. METHODS: Subjects were sampled from 16
      provincial-capital cities in China. They were all Han primary and secondary
      school students aged 7 to 18 years. The increments of stature, weight and BMI,
      and the increments per decade of these indicators at different stages were
      analyzed. RESULTS: In recent 26 years, the overall increments were 6.5 and 4.7 cm
      for stature, and 8.9 and 5.2 kg for weight, for boys and girls, respectively.
      Swiftest rates were found in the period of 1985-1995, with the increments which
      were as high as 3.8 and 3.0 cm/decade for height, and 4.7 and 3.1 kg/decade for
      weight, for boys and girls respectively. These trends are still strong at
      present, without any tendency of going to the plateau. Advanced puberty plays the
      most contributing role in these trends, with the peak height rates being 2.4
      cm/decade for girls at the age of 12 and 3.3 cm/decade for boys at the age of 14,
      respectively. The increments of adult height were 3.2 and 2.1 cm, while the rates
      were 1.2 and 0.8 cm/decade, for males and females, respectively. The distributing
      curves of BMI show an accelerating tendency of going to the right side, which
      suggests that the prevalence of childhood obesity is increasing rapidly.
      CONCLUSION: China is now experiencing an overall and positive secular trend,
      which is reflected not only by the accelerating physical growth in childhood,
      advanced puberty, and steady increments of adult height, but also by the dramatic
      changes of body shape. We should not only feel proud of the achievements of these
      secular growth changes and the active socioeconomic influences, but also pay much
      attention to their negative effects, especially those that may induce the dangers
      of hypertension, hyperglycemia, type 2 diabetes mellitus and other adulthood
      diseases, as well as the disease risks of metabolic syndrome that may even occur
      early in childhood and adolescence.

PMID- 17440585
TI  - [Holistic view on vulnerability of HIV/AIDS infection among youth out of
      schools].
AB  - OBJECTIVE: To expose the vulnerability of HIV/AIDS infection among youth out of
      schools in a holistic view through understanding lifestyle, peer relations,
      awareness of HIV/AIDS, and HIV/AIDS prevention service of the youth. METHODS: A
      cross-sectional survey based on the collective random sampling was conducted
      among 584 youth out of schools with or without a job in Anshan City, Liaoning
      Province in October 2005. RESULTS: The awareness rate of HIV/AIDS among youth out
      of schools was 58.9%, and 65.6% of the subjects never accepted any health service
      related to HIV/AIDS prevention. 42.6% of the respondents had sexual experience,
      and the rate of having sexual experience among males (62.3%) was higher than that
      of females (37.7%). And 30.5% of the youth seldom or never used a condom, 51.2%
      of the youth having sex didn't use a condom in his/her last sex. 28.2% of the
      youth having sex were ever involved in commercial sex relations. 22 of the
      respondents (3.8%) had the experience of drug substance, the rate of having sex
      experience among youth who used the substance was higher than that of the youth
      who never used the substance. Smoking, alcohol abusing, visiting recreation
      places, high month consumption were the risk factors of pre-marital sex, and high
      awareness of HIV/AIDS was the protective factor of pre-marital sex. CONCLUSION:
      The youth out of schools were vulnerable in sexual behavior, substance use, peer
      influencing, social environment, and HIV/AIDS prevention service in terms of
      HIV/AIDS infection.

PMID- 17440586
TI  - [Status of mother's KAP on child immunization in minority areas, Guizhou
      Province].
AB  - OBJECTIVE: To evaluate the status of mothers' knowledge, attitudes and practices
      (KAP) and its related factors and provide evidences for further effective
      implementation on childhood immunization in Guizhou Province. METHODS: This study
      was a cross-sectional study, in which 591 mothers of children under 2 years were
      surveyed with structured questionnaires in six selected counties of Qiandongnan
      Canton. RESULTS: Mothers' knowledge, attitudes and practices on childhood
      immunization were at a low level and influenced by educational background,
      county's economical level, mother's age, household size and ethnic groups. The
      childhood immunization was also at a low level. Among the 290 youngest children
      in a household survey, the coverage rate of all five vaccines (including HBV,
      BCG, OPV, DTP and measles vaccine) was 35.2%, and 12.3% of the surveyed children
      had never been immunized since birth. The main source of knowledge on
      immunization was interpersonal communication. CONCLUSION: Considering mothers'
      poor KAP status and low education level, health education on immunization should
      be implemented though interpersonal communication via assistant media, and
      educating emphases should be laid on some special-characteristics targets.

PMID- 17440587
TI  - [Puerperal practice pattern in a rural area of north China].
AB  - OBJECTIVE: To describe women's behavioral patterns in the period of "doing the
      month" (confinement in childbirth) and to determine the degree of differences
      between "doing the month" practices and daily behaviors. METHODS: A retrospective
      survey was conducted with a random sample of 1,813 women who were interviewed
      using a questionnaire undertaken in May of 2004. RESULTS: The results showed that
      the majority of women adhered to the traditional customs. While "doing the
      month", more than 90% of women did not eat cold, hard, or sour food; more than
      90% of the women did not wash their hair or body at all, and more than 70% of
      women did not brush their teeth or wash their feet. As compared to what women
      normally do, most women drastically changed their practices in eating,
      sanitation, dress, activity, doing chores, and so on, during their "doing the
      month". Further analysis indicated that women's age had no effect on the change
      of practice patterns and that women's education had an inconsequential effect.
      CONCLUSION: The traditional "doing the month" practices are still very popular in
      the rural areas of China. Birth belief, illness concept and traditional village
      culture are the main factors for the pattern of "doing the month".

PMID- 17440588
TI  - [Using diagnosis relative groups mortality risk classification to assess medical
      quality].
AB  - OBJECTIVE: To introduce diagnosis related groups to assess the medical quality
      and try to establish an effective quality evaluation approach. METHODS: Using
      Australia-Refined Diagnosis Related Groups, version 5.0 (AR-DRGs v5.0) to
      classify the 160 000 discharged cases from 7 large hospitals in Beijing in 2005.
      Based on this, mortality risk classification was established to adjust the whole
      hospital risks. And then hospital mortality of all the risk groups from each
      hospital was calculated respectively, which was used as the basic quality
      assessment criterion. The differences between the assessment results from using
      the raw hospital mortality and from using Diagnosis Relative Groups Mortality
      Risk Classification (DRGs-MRC) were compared. RESULTS: (1) The risk types were
      different among the discharged cases in different hospitals; (2) The assessment
      results from these two approaches about No.6 hospital were similar in that No.6
      hospital had a good quality performance; (3) The raw hospital mortality was the
      lowest in No.2 hospital (0.98%), but the mortality of low risk group in this
      hospital was higher than the average level of the same risk group among these 7
      hospitals; the status of No.5 hospital was much the same. CONCLUSION: Compared
      with raw hospital mortality, DRGs-MRC improved the comparability of cases and the
      reliability of the assessment result.

PMID- 17440589
TI  - [Relationship between 5,10-methylenetetrahydrofolate reductase genetic
      polymorphism and arsenic metabolism].
AB  - OBJECTIVE: To study the relationship between 5,10-methylenetetrahydrofolate
      reductase(MTHFR) genetic polymorphism and arsenic metabolism and the role of
      folate in it. METHODS: Forty-three individuals who were exposed to arsenic more
      than 0.05 mg/L in well water were chosen and the vein blood and morning urine was
      collected; The MTHFR C677 polymorphism was analyzed by PCR-RFLP method ; Urinary
      inorganic and methylated arsenic were speciated by high performance liquid
      chromatography combined with hydride-generation atomic fluorescence spectrometry;
      Microbiological assay was used to estimate serum folate. RESULTS: Subjects with
      the genotype of CT/TT had the increased percentage of urinary As3+ (r=27.17,
      P=0.029) and decreased percentage of urinary dimethylarsinic acid (r=26.57,
      P=0.033). No association was observed among serum folate, genetic polymorphisms
      of MTHFR C677 and the percentage of urinary arsenic (P>0.05). CONCLUSION: Genetic
      polymorphism of MTHFR C677 was significantly associated with arsenic methylation
      and this effect was not associated with the serum folate.

PMID- 17440590
TI  - [Concentration-response relationship between particulate air pollution and daily
      mortality in Taiyuan].
AB  - OBJECTIVE: To further study concentration-response relationship between daily
      mortality and particulate air pollution, to provide scientific basis for making
      policy. METHODS: We applied spline model to daily time-series data for Taiyuan
      city, China from 2004-2005, using concentration of particulate matter less than
      10 microm in aerodynamic diameter (PM10) as the exposure measure, and controlling
      confounding factors, such as season, meteorological factors, day-of-the-week,
      other air pollutions, etc. RESULTS: The spline model showed a nonlinear
      relationship for the relative risks of death for all causes (total deaths) and
      for specific causes in relation to PM10 concentration, and obtained threshold
      levels. For total mortality, malignant tumor mortality and cardiovascular
      cerebrovascular-respiratory mortality, the threshold levels were 85.00 microg/m3,
      89.59 microg/m3, 122.54 microg/m3, respectively using the value of differential
      deduction. CONCLUSION: Our nonlinear models are appropriate for assessing the
      effect of particulate air pollution on daily mortality at current ambient levels
      in Taiyuan, China,in contrast to those of Europe and America.

PMID- 17440591
TI  - [Comparative study of heterogeneity of extranodal and nodal diffuse large B cell
      lymphoma].
AB  - OBJECTIVE: Primary nodal and extranodal diffuse large B-cell lymphoma (DLBCL)
      were investigated for the heterogeneity of histopathology and immunophenotype,
      and their relation to clinical stage, comparatively. Whether E2F1 can be used as
      a germinal center B cell (GCB) DLBCL marker was also discussed. METHODS:
      Classification of histopathology and immunophenotype of 98 cases were studied by
      immunohistochemistry in tissue microarray. RESULTS: Histopathologic morphology
      presented as: centroblastic (CB,88.8%, 87/98), immunoblastic (IB,5.1%, 5/98),
      anaplastic (ALCL,3.1%, 3/98), and T cell rich B cell lymphoma (TCRBCL,3.1%,
      3/98). Of which, 31 cases were GCB DLBCL, 10 (20.8%, 10/48) nodal, and 21
      extranodal (42%, 21/50, P=0.024). The rates of Stages I/II in nodal and
      extranodal area were 48.5% and 70%, respectively (P=0.015). The rate of Stage I/
      II in GCB DLBCL (74.2%) were higher than in non-GCB DLBCL (50.7%, P=0.029). The
      CD10 positive rates were 36.8% and 17.1% in Stages I/II and III/IV, respectively,
      and had significant differences (P=0.033). The CD10 positive rates were 18.8% and
      38% in nodal and extranodal area, respectively (P=0.035). The positive rates of
      E2F1 were 38.8% and 16.5% in GCB and non-GCB DLBCL, respectively, and had
      significant differences (P=0.016). The positive rate of E2F1 had positive
      relation with the expression of CD10 and Bcl-6 (P<0.05). CONCLUSION: CB is the
      most type in 98 cases of DLBCL. The rate of GCB DLBCL was significant higher in
      extranodal than in nodal areas CD 10 can be used as a prognostic marker. The
      prognosis of GCB DLBCL is better than that of non-GCB DLBCL. The positive
      expression of E2F1 can be used as a marker of GCB DLBCL.

PMID- 17440592
TI  - [GITR/GITRL expression in peripheral blood of rheumatoid arthritis].
AB  - OBJECTIVE: To explore the expression of GITR/GITRL in rheumatoid arthritis(RA)
      and its correlation with clinical features of the disease. METHODS: Fifty three
      RA patients, 35 osteoarthritis (OA) patients and 35 healthy volunteers were
      included in the study. The real-time-fluorescence quantitative PCR method was
      used to analyze the expression level of GITR/GITRL mRNA. Using fluorescence
      activated cell sorting(FACS), the expression of GITR on CD4+CD25+ T cells in
      peripheral blood monouuclear cells (PBMC) was detected. The levels of Anti-CCP
      antibody, C-reactive protein(CRP), erythrocyte sedimentation rate(ESR) and
      rheumatoid factor (RF) of the RA patients were measured at the same time.
      RESULTS: It was shown that the level of GITR/GITRL mRNA and the percentage of
      GITR+ T cells in the CD4+CD25+ T cell subpopulation[12.38+/-5.72/16.41+/
      10.16,(28.12+/-16.85)%] were significantly higher than those of the OA group
      [9.59+/-5.87/12.09+/-7.53,(21.01+/-14.42)%,P<0.05] and control group [8.75+/
      3.78/11.99+/-8.42,(19.98+/- 9.40)%,P<0.05]. The expression of GITR/GITRL from RA
      patients was positively associated with the level of DAS28 and ESR
      (r=0.361,r=0.427,P<0.01). CONCLUSION: The GITR/GITRL expression of RA patients
      was higher than that of other groups which may play an important role in the
      development of RA.

PMID- 17440593
TI  - [High glucose downregulates the expression of podocalyxin protein in glomerular
      podocytes of mice].
AB  - OBJECTIVE: To examine the expression of podocalyxin protein in glomerular
      podocytes by long-term high glucose exposure in vitro and in vivo. METHODS:
      Immunohistochemical staining and computer image analysis were applied to detect
      the expression of podocalyxin protein in glomeruli from db/db mice and Wt mice.
      The effects of high glucose on the expression of podocalyxin protein were
      analyzed by Western blotting. The activation of MAPKS signaling pathway (ERK, p38
      and JNK) by high glucose was also examined. RESULTS: The expressions of
      podocalyxin protein in db/db mice were obviously less than that in Wt mice
      [(0.18+/-0.07) vs (0.25+/-0.05),P<0.05] assessed by immunostaining and
      semiquantitative analysis. Basal levels of podocalyxin protein were observed in
      cultured mouse podocytes. The level of podocalyxin protein declined at each time
      point by high glucose incubation, reached the lowest level on the 6th day (5.5%
      of control group, P<0.01), but no significant changes were observed in normal
      glucose and mannitol glucose incubation groups. High glucose medium induced
      phosphorylation of ERK1/2 as early as 30 minutes, reached the peak at hour 6;
      maintained the activation from hour 12 to 24, and declined to the basal level at
      hour 48. However, activation of ERK1/2 was not detected in normal glucose and
      mannitol glucose groups. Blockade of activation of ERK1/2 with PD98059, a
      specific ERK1/2 activation inhibitor, attenuated the high glucose-induced
      expression of podocalyxin protein on the 6th day. CONCLUSION: High ambient
      glucose decreases the protein level of podocalyxin by podocyte in vitro and in
      vivo, and the decrease in podocalyxin protein is ERK1/2jdependent in cultured
      podocytes.

PMID- 17440594
TI  - [Inhibitory effect of Adp53 and F56 on growth and metastasis of transplantation
      of the breast tumor in mice].
AB  - OBJECTIVE: To investigate the effects of Adp53 and F56 on the growth and lung
      metastasis of breast cancer. METHODS: The BICR-H1 cells were inoculated into the
      mammary fatty pad of BALB/C nude mice and NOD/SCID mice to establish breast
      cancer model. Then the nude mice with xenograft tumor were randomized into group
      Adp53+F56, Adp53, F56 and control. The NOD/SCID mice with xenograft tumor were
      randomized into group Adp53+F56, Adp53, F56, Adlacz and control. They were
      treated for 3 weeks according to the plan, diversity of the volume and
      histopathology of xenograft tumor of nude mice was observed and the expressions
      of p53 and VEGF gene, and microvessel density (MVD) were detected by
      immunohistochemistry. Lung metastasis of breast cancer in NOD/SCID mice was
      observed. RESULTS: (1) Intratumoral injections of Adp53, F56, and their
      combination resulted in an inhibition on the growth of xenograft tumor of BICR-H1
      cells. The ultimate relative growth volumes of groups Adp53+F56, Adp53, F56 and
      control were 2.47,4.37,4.69 and 12.49 respectively. (2) After treatment, P53
      positive rate of group Adp53+F56, Adp53 increased 9.4%, 6.3% than before
      respectively, but compared with control group, the difference is not significant
      (P=0.693); VEGF protein of group Adp53+F56, Adp53 and F56 decreased 21.9%, 9.4%
      and 3.1% than before respectively, but compared with control group, the
      difference was not significant (P=0.284). Necrosis and decrease of vessel in the
      tumor and morphological change of endothelium were observed under light
      microscope in the groups Adp53+F56, Adp53 and F56. MVD estimated by FVIII-RA
      staining of group Adp53+F56, Adp53 and F56 were 14.50+/-2.54, 16.28+/-3.44 and
      18.06+/-7.66, compared with control group(24.93+/-6.53), the difference is
      significant (P=0.000). (3) The average number of lung metastasis of NOD/SCID mice
      in group Adp53+F56, Adp53 and F56 were 1.143+/-0.378, 2.750+/-0.886 and 3.375+/
      0.518 respectively, lower than Adlacz group(5.000+/-0.816) and control group
      (5.670+/-0.817) obviously (P=0.000). CONCLUSION: Adp53 combined with F56 can
      greatly inhibit growth and metastasis of breast cancer in vivo. The mechanism of
      anti-tumor effects of Adp53 and F56 may be related to the anti-angiogenesis
      effect on malignant tumor through inhibiting the expression and activity of VEGF.

PMID- 17440595
TI  - [Expression of aquaporin 4 during development of experimential presyrinx state in
      rabbits].
AB  - OBJECTIVE: To investigate the expression of AQP4 during the development of
      presyrinx state of experimental syringomyelia in rabbits. METHODS: The
      experimental syringomyelia models of rabbits were established by intra-cisternal
      injection of Kaolin. The expression of AQP4 AQP4mRNA and the water content of
      upper cervical spinal cord were measured with immunohistochemistry Western blot
      RT-PCR and dry-wet measurement on days 1,3,7,14, and 21 after operation,
      respectively. RESULTS: Compared with animals of control group, the water content
      increased in those of Kaolin group from the 1st day (68.35%+/-0.70%), reached its
      peak on the 7th day (72.92%+/-0.86%), lasted to the 14th day (72.58%+/-0.55%),
      and then began to drop on the 21st day (70.03%+/-0.77%), while AQP-4
      immunoreactive expression decreased on the 3rd day [integral optical density(IOD)
      320.5+/-44.2], reached its minimum on the 7th day (IOD 258.7+/-26.5), lasted to
      the 14th day, and recovered partially on the 21st day approximately (IOD 321.5+/
      46.1). RT-PCR found the decreasing of AQP4 mRNA coincided well with that of AQP4
      immunoreactive expression in presyrinx state. The linear regression analysis
      indicated that expression of AQP4 and its mRNA in cervical cord had a negative
      correlation with the change of spinal water content (r=-0.769, P<0.01; r=-0.955,
      P<0.01). CONCLUSION: Downregulation of AQP4 and its mRNA expression may involve
      in edema formation in the presyrinx state of rabbits.

PMID- 17440596
TI  - [Preparation and physicochemical characterization of hydrogel microspheres for
      embolization].
AB  - OBJECTIVE: To develop and characterize the hydrogel microspheres for
      embolization. METHODS: N-[tris (hydroxymethyl) methyl] acrylamide-gelatin
      microspheres (TGMs) were prepared by an inverse suspension polymerization
      approach. Effects of materials on size, water absorption rate and elasticity of
      the microspheres were investigated. The materials which were included consisted
      of gelatin in the range of 10.0-100.0 g/L, N-[tris
      (hydroxymethyl)methyl]acrylamide in the range of 33.3-200 g/L, cross-linking
      agent N,N'-methylene-bis-acrylamide in the range of 3.3-10.0 g/L, surfactant Span
      80 in the range of 0.5-1.8 g/L, and initiator ammonium persulfate in the range of
      1.0-5.0 g/L. The appearance of TGMs was observed under microscope. TGMs were
      analyzed by infrared spectrum (IR). RESULTS: The TGMs were round with smooth
      surface in view of photograph of microscope. The average diameter of TGMs was
      increased with the increase of gelatin, monomer or cross-linking agent
      concentrations but decreased with the increase of surfactant or initiator
      Concentration. The water adsorption rate of the microspheres was decreased with
      the increase of gelatin or cross-linking agent concentration but not affected by
      surfactant concentration. The elasticity of TGMs was increased with the increase
      of monomer or cross-linking agent concentration, decreased with the increase of
      gelatin concentration, but not affected by surfactant or initiator concentration.
      All factors above considered, the final prepared TGMs consisted of 10 g/L
      gelatin, 100.0 g/L monomer, 6.7 g/L cross-linking agent, 0.9 g/L surfactant, and
      3.0 g/L initiator. The average diameter of TGMs obtained was about 700.0 microm.
      The water adsorption rate and the elasticity in accordance with the maximum
      diameter of the microspheres passed through a microcatheter of TGMs were 12.4
      (g/g), and 1 600.0 microm, respectively. The results of IR spectra confirmed the
      polymerization of monomer, resulting in
      Nj[tris(hydroxymethyl)methyl]acrylamidegelatin microspheres. CONCLUSION: The
      developed TGMs seemed to be suitable for clinical embolization according to the
      surface, average diameter, elastic and hydrophilic property of TGMs.

PMID- 17440597
TI  - [Application and results of Robicsek procedure for dilated ascending aorta
      associated with aortic valve disease].
AB  - OBJECTIVE: To introduce the Robicsek procedure and summarize its short to mid
      term results for patients with dilatation of the ascending aorta associated with
      aortic valve disease. METHODS: From December 2002 to June 2006, 30 patients with
      a moderately dilated ascending aorta [mean diameter, (46.7+/-3.1) mm] underwent
      concomitant aortic valve replacement (AVR) or repairing and reinforced
      aortoplasty with a well-tailored Dacron vascular graft. Follow-up was obtained on
      all patients with ultrasonic cardiography (UCG) or computed tomography (CT) scan
      and was (18.0+/-10.5) months. RESULTS: The total average cardio-pulmonary bypass
      (CPB) time was (103.4+/-21.7) min (80-151 min), and aortic arrest time was
      (73.0+/-21.6) min (48-120 min), whereas the average CPB time and aortic arrest
      time of 19 patients who underwent the isolated Robicsek procedure were only
      (91.3+/-8.9) min (80-118 min) and (61.6+/-11.3) min (48-82 min). No mortality
      occurred in the hospital. During follow-up of 18 months, no recurrent ascending
      aortic dilatation and dissection were observed, and the average aortic diameter
      was reduced to (33.7+/-2.5) mm. Sixteen of the 30 patients were diagnosed as
      bicuspid aortic valve (BAV). The ascending aortic media were histologically
      abnormal in 23 patients. CONCLUSION: Considering the underlying wall deficiency
      and the homodynamic stress, the Robicsek operation should be an optimal choice to
      those patients with a mild to moderate dilated ascending aorta caused by aortic
      valve lesion. Compared with the Bentall and David procedures, the Robicsek
      procedure could achieve the same or even better clinical results with less
      operative time and risks.

PMID- 17440598
TI  - [Clinical features and dynamics of cervical magnetic resonance imaging in
      Hirayama disease].
AB  - OBJECTIVE: to investigate the clinical feature and dynamic changes of the
      cervical dural sac and spinal cord during neck flexion in Hirayama disease
      (juvenile muscular atrophy of distal upper extremity). METHODS: Clinical data
      were taken and MRI in neutral neck position and a fully flexed neck position were
      performed on 27 cases of Hirayama disease. RESULTS: (1) All patients were
      consistent with the diagnostic criteria of Hirayama disease who had asymmetric
      muscular atrophy and weakness of the hand and forearm. All patients were young
      males and right handed of whom 77.8% had initial symptoms before they were 19
      years old. More patients(20 cases,74%e had muscular atrophy in the right hand
      than in the left at onset. The duration after disease onset was from 2-72
      months[(26.48+/-15.57) months]. (2) In neutral neck position by MIR examination,
      16 patients showed abnormal cervical curvature, 14 showed atrophy of the lower
      cervical cord and 2 patients had intramedullary abnormal high signal. (3) In a
      fully flexed position of the neck, all patients showed forward displacement and
      flattening of the lower cervical cord, and a crescent-shaped high signal area
      behind the cord. (4) The crescent shaped area was enhanced on T1-weighed imaging
      and disappeared after the patient returned to a neural position in one case.
      CONCLUSION: Hirayama disease occurs mainly in young males. There are obviously
      dynamic changes of the cervical cord during neck flexion in Hirayama disease by
      MRI examination, which can help the doctor make diagnosis in the early stage.

PMID- 17440599
TI  - [Clinical study of aromatase inhibitors in advanced breast cancer].
AB  - OBJECTIVE: To assess the antitumor activity and safety of aromatase inhibitors in
      advanced breast cancer. METHODS: Fifty-two advanced and female breast cancer
      patients with measurable and /or bone valuable tumor lesions were observed from
      June 2003 to September 2006. They were treated by aromatase inhibitors for at
      least 24 weeks, of whom 11 were treated less than 24 weeks because of disease
      progress; their age range was from 37 to 75 years (median 58); 8 patients were
      pre-menopausal, 6 with ovarian ablation and 2 with Goserelin to suppress ovarian
      function. Thirty-six patients were treated with exemestane, 13 with anastrozole
      and 3 with letrozole. Major items were observed including objective response rate
      (ORR=CR+PR), clinical benefit rate (CBR=CR+PR+SD>or=24 weeks), time to progress
      (TTP), time to failure (TTF), safety and toxicity. RESULTS: CR were 6 cases
      (11.5%) , with 1 case going on for 152 weeks, 1 case for 96 weeks, and other 4
      cases for longer than 60 weeks; PR were 19 cases (36.5%), lasting 32-96 weeks; 16
      cases obtained SD>or=24 weeks(30.8%); and 11 cases PD (progress of disease)+SD<24
      weeks (21.2%). ORR were 48%, CBR 78.8%, and TTP 78.87 weeks (95% CI 61.13%
      96.61%); although the patients who did not achieve objective response (group B)
      were treated with chemotherapy, radiotherapy or another kind of aromatase
      inhibitor, but their survival time was significantly different from that of the
      patients who achieved objective response (group A) when defined by Kaplan-Meier
      survival estimate. The over survival was 92% in group A, and 81.5% in group B
      when patients follow up more than 24 weeks [Log Rank (Mantel-Cox) analysis,
      chi2=3.85, P=0.047]; side effects were observed such as arthralgia, sweating, hot
      flash, and 2 patients developed heart failure with uncertain related drug before
      recovery. CONCLUSION: The single agent effective rate of aromatase inhibitor was
      48%. The patients had long term survival if they obtained CR or PR, and the side
      effects were well tolerated.

PMID- 17440600
TI  - [Studies of the physiological function of carbonic anhydrase].
AB  - Carbonic anhydrases (CA) is a zinc-enzyme family. They are involved in multiple
      aspects of systemic and cellular acid-base balance. This review is a general
      introduction to the disposition, molecular constitution,biological function and
      physiological function of CA.

PMID- 17440601
TI  - Threat-Sensitive Behavioral Responses to Concentrations of Water-Borne Cues from
      Predation.
AB  - Aquatic organisms often detect predators via water-borne chemical cues, and
      respond by showing reduced activity. Prey responses may be correlated with the
      concentration of predation cues, which would result in graded antipredator
      behavioral responses that adjust potentially costly behavioral changes to levels
      that are commensurate with the risk of predation. Larvae of the predatory
      mosquito Toxorhynchites rutilus prey upon other container-dwelling insects,
      including larvae of the mosquito Ochlerotatus triseriatus. Previous work has
      established that O. triseriatus reduce movement, foraging, and time below the
      surface, and increase the frequency of resting at the surface, in the presence of
      water-borne cues from predation by T. rutilus. We tested whether these responses
      by O. triseriatus are threat sensitive by recording behavior of fourth instar
      larvae in two runs of an experiment in which we created a series of
      concentrations (100, 10, 1, 0.1, and 0.01% and 100, 70, 40, 20, and 10%) of water
      that had held either O. triseriatus larvae alone (control) or a T. rutilus larva
      feeding on O. triseriatus (predation). We also tested whether associated effects
      on time spent feeding are threat sensitive by determining whether frequencies of
      filtering or browsing are also related to concentration of cues. The frequencies
      of resting and surface declined, whereas frequency of filtering (but not
      browsing) increased more rapidly with a decrease in concentration of predation
      cues compared with control cues. Thus, O. triseriatus shows a threat sensitive
      behavioral response to water-borne cues from this predator, adjusting its degree
      of behavioral response to the apparent risk of predation.

PMID- 17440602
TI  - Abnormal Beckmann fragmentation/ring closing metathesis route for preparation of
      18-nor-Delta-androgens and their 18-nor-13,17-epoxide derivatives.
AB  - The synthesis of Delta(13,(17))-androgens and the structurally related 13,17
      epoxides is described. The synthetic route involves cleavage of 17-ketosteroids
      by an abnormal Beckmann rearrangement, modification of the D-ring cleavage
      product to obtained an intermediate tricyclic diene and ring closing metathesis
      of the diene to the Delta(13,(17))-androgen. (3alpha,5alpha)-Androst-13(17)-en-3
      ol and the derivative 13alpha,17alpha- and 13beta,17beta- epoxides were prepared
      by this route.

PMID- 17440603
TI  - A novel strategy for the solid-phase synthesis of cyclic lipodepsipeptides.
AB  - A rapid and efficient Fmoc solid-phase synthesis of cyclic lipodepsipeptide
      analogue 1 to antibiotic fusaricidin A is described. Our synthetic approach
      includes resin attachment of the first amino acid via side chain, successful use
      of combination of four quasi-orthogonal removable protecting groups, stepwise
      solid-phase synthesis of linear peptide analogue, lipid tail attachment followed
      by depsipeptide bond formation and on-resin head-to-tail cyclization. Undesired O
      >N acyl shift, which may occur during Fmoc removal, was successfully avoided by
      the incorporation of the lipid tail into the linear peptide precursor prior to on
      resin depsipeptide bond formation and the ring closure.

PMID- 17440604
TI  - Ketamine Injection among High Risk Youth: Preliminary Findings from New York
      City.
AB  - Ketamine, a synthetic drug commonly consumed by high risk youth, produces a range
      of experiences, including sedation, dissociation, and hallucinations. While
      ketamine is more typically sniffed, we describe a small sample of young ketamine
      injectors (n=25) in New York City and highlight risks associated with this
      emerging type of injection drug use. Our findings indicate that the injection
      practices, injection groups, and use norms surrounding ketamine often differ from
      other injection drug use: intramuscular injections were more common than
      intravenous injections; injection groups were often large; multiple injections
      within a single episode were common; bottles rather than cookers were shared; and
      the drug was often obtained for free. Our findings suggest that the drug
      injection practices exercised by ketamine injectors place them at risk for
      bloodborne pathogens, such as HIV, HBV, and HCV. We conclude that ketamine
      injectors represent an emerging, though often hidden, population of injection
      drug users, particularly among high risk, street-involved youth.

PMID- 17440606
TI  - Dipstick for rapid diagnosis of Shigella flexneri 2a in stool.
AB  - BACKGROUND: Shigellosis or bacillary dysentery, an acute bloody diarrhoea, is a
      major public health burden in developing countries. In the absence of prompt and
      appropriate treatment, the infection is often fatal, particularly in young
      malnourished children. Here, we describe a new diagnostic test for rapid
      detection, in stool, at the bedside of patients, of Shigella flexneri 2a, the
      most predominant agent of the endemic form of the disease. METHODOLOGY/PRINCIPAL
      FINDINGS: The test is based on the detection of S.flexneri 2a lipopolysaccharide
      (LPS) using serotype 2a-specific monoclonal antibodies coupled to gold particles
      and displayed on one-step immunochromatographic dipstick. A concentration as low
      as 20 ng/ml of LPS is detected in distilled water and in reconstituted stools in
      under 15 minutes. The threshold of detection corresponds to a concentration of
      5x10(7) CFU/ml of S. flexneri 2a, which provides an unequivocal positive reaction
      in three minutes in distilled water and reconstituted stools. The specificity is
      100% when tested with a battery of Shigella and unrelated strains, in culture.
      When tested in Vietnam, on clinical samples, the specificity and sensitivity were
      99.2 and 91.5%, respectively. A decrease of the sensitivity during the evaluation
      on stool samples was observed after five weeks at room temperature and was due to
      moistening of the dipsticks caused by the humidity of the air during the fifth
      week of the evaluation. This drawback is now overcome by improving the packaging
      and providing dipsticks individually wrapped in waterproof bags. CONCLUSION: This
      simple dipstick-bases test represents a powerful tool for case management and
      epidemiological surveys.

PMID- 17440607
TI  - Increased neural activity of a mushroom body neuron subtype in the brains of
      forager honeybees.
AB  - Honeybees organize a sophisticated society, and the workers transmit information
      about the location of food sources using a symbolic dance, known as 'dance
      communication'. Recent studies indicate that workers integrate sensory
      information during foraging flight for dance communication. The neural mechanisms
      that account for this remarkable ability are, however, unknown. In the present
      study, we established a novel method to visualize neural activity in the honeybee
      brain using a novel immediate early gene, kakusei, as a marker of neural
      activity. The kakusei transcript was localized in the nuclei of brain neurons and
      did not encode an open reading frame, suggesting that it functions as a non
      coding nuclear RNA. Using this method, we show that neural activity of a mushroom
      body neuron subtype, the small-type Kenyon cells, is prominently increased in the
      brains of dancer and forager honeybees. In contrast, the neural activity of the
      two mushroom body neuron subtypes, the small-and large-type Kenyon cells, is
      increased in the brains of re-orienting workers, which memorize their hive
      location during re-orienting flights. These findings demonstrate that the small
      type Kenyon cell-preferential activity is associated with foraging behavior,
      suggesting its involvement in information integration during foraging flight,
      which is an essential basis for dance communication.

PMID- 17440608
TI  - Hepatitis C virus infection in Guinea-Bissau: a sexually transmitted genotype 2
      with parenteral amplification?
AB  - BACKGROUND: Sub-Saharan Africa is the continent with the highest prevalence of
      Hepatitis C virus (HCV) infection. Genotype 2 HCV is thought to have originated
      from West Africa several hundred years ago. Mechanisms of transmission remain
      poorly understood. METHODOLOGY/PRINCIPAL FINDINGS: To delineate mechanisms for
      HCV transmission in West Africa, we conducted a cross-sectional survey of
      individuals aged >or=50 years in Bissau, Guinea-Bissau. Dried blood spots were
      obtained for HCV serology and PCR amplification. Prevalence of HCV was 4.4%
      (47/1066) among women and 5.0% (27/544) among men. In multivariate analysis, the
      independent risk factors for HCV infection were age (baseline: 50-59 y; 60-69 y,
      adjusted odds ratio [AOR]: 1.67, 95% CI: 0.91-3.06; >or=70 y, AOR: 3.47, 95% CI:
      1.89-6.39), belonging to the Papel, Mancanha, Balanta or Mandjako ethnic groups
      (AOR: 2.45, 95% CI:1.32-4.53), originating from the Biombo, Cacheu or Oio regions
      north of Bissau (AOR: 4.16, 95% CI: 1.18-14.73) and having bought or sold sexual
      services (AOR: 3.60, 95% CI: 1.88-6.89). Of 57 isolates that could be genotyped,
      56 were genotype 2. CONCLUSIONS: Our results suggest that transmission of HCV
      genotype 2 in West Africa occurs through sexual intercourse. In specific
      locations and subpopulations, medical interventions may have amplified
      transmission parenterally.

PMID- 17440609
TI  - Neurosphere-derived cells exert a neuroprotective action by changing the ischemic
      microenvironment.
AB  - BACKGROUND: Neurosphere-derived cells (NC), containing neural stem cells, various
      progenitors and more differentiated cells, were obtained from newborn C57/BL6
      mice and infused in a murine model of focal ischemia with reperfusion to
      investigate if: 1) they decreased ischemic injury and restored brain function; 2)
      they induced changes in the environment in which they are infused; 3) changes in
      brain environment consequent to transient ischemia were relevant for NC action.
      METHODOLOGY/PRINCIPAL FINDINGS: NC were infused intracerebroventricularly 4 h or
      7 d after 30 min middle cerebral artery occlusion. In ischemic mice receiving
      cells at 4 h, impairment of open field performance was significantly improved and
      neuronal loss significantly reduced 7-14 d after ischemia compared to controls
      and to ischemic mice receiving cells at 7 d. Infusion of murine foetal fibroblast
      in the same experimental conditions was not effective. Assessment of infused cell
      distribution revealed that they migrated from the ventricle to the parenchyma,
      progressively decreased in number but they were observable up to 14 d. In mice
      receiving NC at 7 d and in sham-operated mice, few cells could be observed only
      at 24 h, indicating that the survival of these cells in brain tissue relates to
      the ischemic environment. The mRNA expression of trophic factors such as Insulin
      Growth Factor-1, Vascular Endothelial Growth Factor-A, Transforming Growth Factor
      beta1, Brain Derived Neurotrophic Factor and Stromal Derived Factor-1alpha, as
      well as microglia/macrophage activation, increased 24 h after NC infusion in
      ischemic mice treated at 4 h compared to sham-operated and to mice receiving
      cells at 7 d. CONCLUSIONS/SIGNIFICANCE: NC reduce functional impairment and
      neuronal damage after ischemia/reperfusion injury. Several lines of evidence
      indicate that the reciprocal interaction between NC and the ischemic environment
      is crucial for NC protective actions. Based on these results we propose that a
      bystander control of the ischemic environment may be the mechanism used by NC to
      rapidly restore acutely injured brain function.

PMID- 17440611
TI  - Mechanisms of TSC-mediated control of synapse assembly and axon guidance.
AB  - Tuberous sclerosis complex is a dominant genetic disorder produced by mutations
      in either of two tumor suppressor genes, TSC1 and TSC2; it is characterized by
      hamartomatous tumors, and is associated with severe neurological and behavioral
      disturbances. Mutations in TSC1 or TSC2 deregulate a conserved growth control
      pathway that includes Ras homolog enriched in brain (Rheb) and Target of
      Rapamycin (TOR). To understand the function of this pathway in neural
      development, we have examined the contributions of multiple components of this
      pathway in both neuromuscular junction assembly and photoreceptor axon guidance
      in Drosophila. Expression of Rheb in the motoneuron, but not the muscle of the
      larval neuromuscular junction produced synaptic overgrowth and enhanced synaptic
      function, while reductions in Rheb function compromised synapse development.
      Synapse growth produced by Rheb is insensitive to rapamycin, an inhibitor of Tor
      complex 1, and requires wishful thinking, a bone morphogenetic protein receptor
      critical for functional synapse expansion. In the visual system, loss of Tsc1 in
      the developing retina disrupted axon guidance independently of cellular growth.
      Inhibiting Tor complex 1 with rapamycin or eliminating the Tor complex 1
      effector, S6 kinase (S6k), did not rescue axon guidance abnormalities of Tsc1
      mosaics, while reductions in Tor function suppressed those phenotypes. These
      findings show that Tsc-mediated control of axon guidance and synapse assembly
      occurs via growth-independent signaling mechanisms, and suggest that Tor complex
      2, a regulator of actin organization, is critical in these aspects of neuronal
      development.

PMID- 17440610
TI  - Evolution of axis specification mechanisms in jawed vertebrates: insights from a
      chondrichthyan.
AB  - The genetic mechanisms that control the establishment of early polarities and
      their link with embryonic axis specification and patterning seem to substantially
      diverge across vertebrates. In amphibians and teleosts, the establishment of an
      early dorso-ventral polarity determines both the site of axis formation and its
      rostro-caudal orientation. In contrast, amniotes retain a considerable plasticity
      for their site of axis formation until blastula stages and rely on signals
      secreted by extraembryonic tissues, which have no clear equivalents in the
      former, for the establishment of their rostro-caudal pattern. The rationale for
      these differences remains unknown. Through detailed expression analyses of key
      development genes in a chondrichthyan, the dogfish Scyliorhinus canicula, we have
      reconstructed the ancestral pattern of axis specification in jawed vertebrates.
      We show that the dogfish displays compelling similarities with amniotes at
      blastula and early gastrula stages, including the presence of clear homologs of
      the hypoblast and extraembryonic ectoderm. In the ancestral state, these
      territories are specified at opposite poles of an early axis of bilateral
      symmetry, homologous to the dorso-ventral axis of amphibians or teleosts, and
      aligned with the later forming embryonic axis, from head to tail. Comparisons
      with amniotes suggest that a dorsal expansion of extraembryonic ectoderm,
      resulting in an apparently radial symmetry at late blastula stages, has taken
      place in their lineage. The synthesis of these results with those of functional
      analyses in model organisms supports an evolutionary link between the dorso
      ventral polarity of amphibians and teleosts and the embryonic-extraembryonic
      organisation of amniotes. It leads to a general model of axis specification in
      gnathostomes, which provides a comparative framework for a reassessment of
      conservations both among vertebrates and with more distant metazoans.

PMID- 17440612
TI  - Sleep enforces the temporal order in memory.
AB  - BACKGROUND: Temporal sequence represents the main principle underlying episodic
      memory. The storage of temporal sequence information is thought to involve
      hippocampus-dependent memory systems, preserving temporal structure possibly via
      chaining of sequence elements in heteroassociative networks. Converging evidence
      indicates that sleep enhances the consolidation of recently acquired
      representations in the hippocampus-dependent declarative memory system. Yet, it
      is unknown if this consolidation process comprises strengthening of the temporal
      sequence structure of the representation as well, or is restricted to sequence
      elements independent of their temporal order. To address this issue we tested the
      influence of sleep on the strength of forward and backward associations in word
      triplets. METHODOLOGY/PRINCIPAL FINDINGS: Subjects learned a list of 32 triplets
      of unrelated words, presented successively (A-B-C) in the center of a screen, and
      either slept normally or stayed awake in the subsequent night. After two days,
      retrieval was assessed for the triplets sequentially either in a forward
      direction (cueing with A and B and asking for B and C, respectively) or in a
      backward direction (cueing with C and B and asking for B and A, respectively).
      Memory was better for forward than backward associations (p<0.01). Sleep did not
      affect backward associations, but enhanced forward associations, specifically for
      the first (AB) transitions (p<0.01), which were generally more difficult to
      retrieve than the second transitions. CONCLUSIONS/SIGNIFICANCE: Our data
      demonstrate that consolidation during sleep strengthens the original temporal
      sequence structure in memory, presumably as a result of a replay of new
      representations during sleep in forward direction. Our finding suggests that the
      temporally directed replay of memory during sleep, apart from strengthening those
      traces, could be the key mechanism that explains how temporal order is integrated
      and maintained in the trace of an episodic memory.

PMID- 17440613
TI  - Established risk factors account for most of the racial differences in
      cardiovascular disease mortality.
AB  - BACKGROUND: Cardiovascular disease (CVD) mortality varies across racial and
      ethnic groups in the U.S., and the extent that known risk factors can explain the
      differences has not been extensively explored. METHODS: We examined the risk of
      dying from acute myocardial infarction (AMI) and other heart disease (OHD) among
      139,406 African-American (AA), Native Hawaiian (NH), Japanese-American (JA),
      Latino and White men and women initially free from cardiovascular disease
      followed prospectively between 1993-1996 and 2003 in the Multiethnic Cohort Study
      (MEC). During this period, 946 deaths from AMI and 2,323 deaths from OHD were
      observed. Relative risks of AMI and OHD mortality were calculated accounting for
      established CVD risk factors: body mass index (BMI), hypertension, diabetes,
      smoking, alcohol consumption, amount of vigorous physical activity, educational
      level, diet and, for women, type and age at menopause and hormone replacement
      therapy (HRT) use. RESULTS: Established CVD risk factors explained much of the
      observed racial and ethnic differences in risk of AMI and OHD mortality. After
      adjustment, NH men and women had greater risks of OHD than Whites (69% excess,
      P<0.001 and 62% excess, P = 0.003, respectively), and AA women had greater risks
      of AMI (48% excess, P = 0.01) and OHD (35% excess, P = 0.007). JA men had lower
      risks of AMI (51% deficit, P<0.001) and OHD (27% deficit, P = 0.001), as did JA
      women (AMI, 37% deficit, P = 0.03; OHD, 40% deficit, P = 0.001). Latinos had
      underlying lower risk of AMI death (26% deficit in men and 35% in women, P =
      0.03). CONCLUSION: Known risk factors explain the majority of racial and ethnic
      differences in mortality due to AMI and OHD. The unexplained excess in NH and AA
      and the deficits in JA suggest the presence of unmeasured determinants for
      cardiovascular mortality that are distributed unequally across these populations.

PMID- 17440614
TI  - Model structure of human APOBEC3G.
AB  - BACKGROUND: APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide
      like 3G) has antiretroviral activity associated with the hypermutation of viral
      DNA through cytosine deamination. APOBEC3G has two cytosine deaminase (CDA)
      domains; the catalytically inactive amino-terminal domain of APOBEC3G (N-CDA)
      carries the Vif interaction domain. There is no 3-D structure of APOBEC3G solved
      by X-ray or nuclear magnetic resonance. METHODOLOGY/PRINCIPAL FINDINGS: We
      predicted the structure of human APOBEC3G based on the crystal structure of
      APOBEC2. To assess the model structure, we evaluated 48 mutants of APOBEC3G N-CDA
      that identify novel variants altering DeltaVif HIV-1 infectivity and packaging of
      APOBEC3G. Results indicated that the key residue D128 is exposed at the surface
      of the model, with a negative local electrostatic potential. Mutation D128K
      changes the sign of that local potential. In addition, two novel functionally
      relevant residues that result in defective APOBEC3G encapsidation, R122 and W127,
      cluster at the surface. CONCLUSIONS/SIGNIFICANCE: The structure model identifies
      a cluster of residues important for packaging of APOBEC3G into virions, and may
      serve to guide functional analysis of APOBEC3G.

PMID- 17440615
TI  - Divergent evolution among teleost V1r receptor genes.
AB  - The survival of vertebrate species is dependent on the ability of individuals to
      adequately interact with each other, a function often mediated by the olfactory
      system. Diverse olfactory receptor repertoires are used by this system to
      recognize chemicals. Among these receptors, the V1rs, encoded by a very large
      gene family in most mammals, are able to detect pheromones. Teleosts, which also
      express V1r receptors, possess a very limited V1r repertoire. Here, taking
      advantage of the possibility to unequivocally identify V1r orthologs in teleosts,
      we analyzed the olfactory expression and evolutionary constraints of a pair of
      clustered fish V1r receptor genes, V1r1 and V1r2. Orthologs of the two genes were
      found in zebrafish, medaka, and threespine stickleback, but a single
      representative was observed in tetraodontidae species. Analysis of V1r1 and V1r2
      sequences from 12 different euteleost species indicate different evolutionary
      rates between the two paralogous genes, leading to a highly conserved V1r2 gene
      and a V1r1 gene under more relaxed selective constraint. Moreover, positively
      selected sites were detected in specific branches of the V1r1 clade. Our results
      suggest a conserved agonist specificity of the V1R2 receptor between euteleost
      species, its loss in the tetraodontidae lineage, and the acquisition of different
      chemosensory characteristics for the V1R1 receptor.

PMID- 17440616
TI  - A novel approach for determining cancer genomic breakpoints in the presence of
      normal DNA.
AB  - CDKN2A (encodes p16(INK4A) and p14(ARF)) deletion, which results in both Rb and
      p53 inactivation, is the most common chromosomal anomaly in human cancers. To
      precisely map the deletion breakpoints is important to understanding the
      molecular mechanism of genomic rearrangement and may also be useful for clinical
      applications. However, current methods for determining the breakpoint are either
      of low resolution or require the isolation of relatively pure cancer cells, which
      can be difficult for clinical samples that are typically contaminated with
      various amounts of normal host cells. To overcome this hurdle, we have developed
      a novel approach, designated Primer Approximation Multiplex PCR (PAMP), for
      enriching breakpoint sequences followed by genomic tiling array hybridization to
      locate the breakpoints. In a series of proof-of-concept experiments, we were able
      to identify cancer-derived CDKN2A genomic breakpoints when more than 99.9% of
      wild type genome was present in a model system. This design can be scaled up with
      bioinformatics support and can be applied to validate other candidate cancer
      associated loci that are revealed by other more systemic but lower throughput
      assays.

PMID- 17440617
TI  - ElaD, a Deubiquitinating protease expressed by E. coli.
AB  - BACKGROUND: Ubiquitin and ubiquitin-like proteins (Ubl) are designed to modify
      polypeptides in eukaryotes. Covalent binding of ubiquitin or Ubls to substrate
      proteins can be reversed by specific hydrolases. One particular set of cysteine
      proteases, the CE clan, which targets ubiquitin and Ubls, has homologs in
      eukaryotes, prokaryotes, and viruses. FINDINGS: We have cloned and analyzed the
      E. coli protein elaD, which is distantly related to eukaryotic CE clan members of
      the ULP/SENP protease family that are specific for SUMO and Nedd8. Previously
      misannotated as a putative sulfatase/phosphatase, elaD is an efficient and
      specific deubiquitinating enzyme in vitro. Interestingly, elaD is present in all
      intestinal pathogenic E. coli strains, but conspicuously absent from
      extraintestinal pathogenic strains (ExPECs). Further homologs of this protease
      can be found in Acanthamoeba Polyphaga Mimivirus, and in Alpha-, Beta-and
      Gammaproteobacteria. CONCLUSION: The expression of ULP/SENP-related hydrolases in
      bacteria therefore extends to plant pathogens and medically relevant strains of
      Escherichia coli, Legionella pneumophila, Rickettsiae, Chlamydiae, and
      Salmonellae, in which the elaD ortholog sseL has recently been identified as a
      virulence factor with deubiquitinating activity. As a counterpoint, our
      phylogenetic and functional examination reveals that ancient eukaryotic ULP/SENP
      proteases also have the potential of ubiquitin-specific hydrolysis, suggesting an
      early common origin of this peptidase clan.

PMID- 17440618
TI  - Periodic accumulation of regulatory T cells in the uterus: preparation for the
      implantation of a semi-allogeneic fetus?
AB  - BACKGROUND: Naturally occurring Foxp3(+)regulatory T cells play an important role
      in the inhibition of an immunological attack of the fetus. As implantation of the
      fetus poses an immediate antigenic challenge, the immune system has to prepare
      itself for this event prior to implantation. METHODOLOGY AND PRINCIPAL FINDINGS:
      Here, we show using quantitative RT-PCR and flow cytometry that regulatory T
      cells accumulate in the uterus not only during pregnancy, but also every time the
      female becomes fertile. Their periodic accumulation is accompanied by matching
      fluctuations in uterine expression of several chemokines, which have been shown
      to play a role in the recruitment and retention of regulatory T cells.
      CONCLUSIONS/SIGNIFICANCE: The data lead us to propose that every time a female
      approaches estrus, regulatory T cells start to accumulate in the uterus in
      preparation for a possible implantation event. Once pregnancy is established,
      those regulatory T cells that have seen alloantigen need to be retained at their
      site of action. Whilst several chemokines appear to be involved in the
      recruitment and/or retention of regulatory T cells during estrus, in pregnancy
      this role appears to be taken over by CCL4.

PMID- 17440619
TI  - Assessing performance of orthology detection strategies applied to eukaryotic
      genomes.
AB  - Orthology detection is critically important for accurate functional annotation,
      and has been widely used to facilitate studies on comparative and evolutionary
      genomics. Although various methods are now available, there has been no
      comprehensive analysis of performance, due to the lack of a genomic-scale 'gold
      standard' orthology dataset. Even in the absence of such datasets, the comparison
      of results from alternative methodologies contains useful information, as
      agreement enhances confidence and disagreement indicates possible errors. Latent
      Class Analysis (LCA) is a statistical technique that can exploit this information
      to reasonably infer sensitivities and specificities, and is applied here to
      evaluate the performance of various orthology detection methods on a eukaryotic
      dataset. Overall, we observe a trade-off between sensitivity and specificity in
      orthology detection, with BLAST-based methods characterized by high sensitivity,
      and tree-based methods by high specificity. Two algorithms exhibit the best
      overall balance, with both sensitivity and specificity>80%: INPARANOID identifies
      orthologs across two species while OrthoMCL clusters orthologs from multiple
      species. Among methods that permit clustering of ortholog groups spanning
      multiple genomes, the (automated) OrthoMCL algorithm exhibits better within-group
      consistency with respect to protein function and domain architecture than the
      (manually curated) KOG database, and the homolog clustering algorithm TribeMCL as
      well. By way of using LCA, we are also able to comprehensively assess
      similarities and statistical dependence between various strategies, and evaluate
      the effects of parameter settings on performance. In summary, we present a
      comprehensive evaluation of orthology detection on a divergent set of eukaryotic
      genomes, thus providing insights and guides for method selection, tuning and
      development for different applications. Many biological questions have been
      addressed by multiple tests yielding binary (yes/no) outcomes but no clear
      definition of truth, making LCA an attractive approach for computational biology.

PMID- 17440620
TI  - Robust time estimation reconciles views of the antiquity of placental mammals.
AB  - BACKGROUND: Molecular studies have reported divergence times of modern placental
      orders long before the Cretaceous-Tertiary boundary and far older than
      paleontological data. However, this discrepancy may not be real, but rather
      appear because of the violation of implicit assumptions in the estimation
      procedures, such as non-gradual change of evolutionary rate and failure to
      correct for convergent evolution. METHODOLOGY/PRINCIPAL FINDINGS: New procedures
      for divergence-time estimation robust to abrupt changes in the rate of molecular
      evolution are described. We used a variant of the multidimensional vector space
      (MVS) procedure to take account of possible convergent evolution. Numerical
      simulations of abrupt rate change and convergent evolution showed good
      performance of the new procedures in contrast to current methods. Application to
      complete mitochondrial genomes identified marked rate accelerations and
      decelerations, which are not obtained with current methods. The root of placental
      mammals is estimated to be approximately 18 million years more recent than when
      assuming a log Brownian motion model. Correcting the pairwise distances for
      convergent evolution using MVS lowers the age of the root about another 20
      million years compared to using standard maximum likelihood tree branch lengths.
      These two procedures combined revise the root time of placental mammals from
      around 122 million years ago to close to 84 million years ago. As a result, the
      estimated distribution of molecular divergence times is broadly consistent with
      quantitative analysis of the North American fossil record and traditional
      morphological views. CONCLUSIONS/SIGNIFICANCE: By including the dual effects of
      abrupt rate change and directly accounting for convergent evolution at the
      molecular level, these estimates provide congruence between the molecular
      results, paleontological analyses and morphological expectations. The programs
      developed here are provided along with sample data that reproduce the results of
      this study and are especially applicable studies using genome-scale sequence
      lengths.

PMID- 17440621
TI  - Genome-wide studies of histone demethylation catalysed by the fission yeast
      homologues of mammalian LSD1.
AB  - In order to gain a more global view of the activity of histone demethylases, we
      report here genome-wide studies of the fission yeast SWIRM and polyamine oxidase
      (PAO) domain homologues of mammalian LSD1. Consistent with previous work we find
      that the two S. pombe proteins, which we name Swm1 and Swm2 (after SWIRM1 and
      SWIRM2), associate together in a complex. However, we find that this complex
      specifically demethylates lysine 9 in histone H3 (H3K9) and both up- and down
      regulates expression of different groups of genes. Using chromatin
      immunoprecipitation, to isolate fragments of chromatin containing either H3K4me2
      or H3K9me2, and DNA microarray analysis (ChIP-chip), we have studied genome-wide
      changes in patterns of histone methylation, and their correlation with gene
      expression, upon deletion of the swm1(+) gene. Using hyper-geometric probability
      comparisons we uncover genetic links between lysine-specific demethylases, the
      histone deacetylase Clr6, and the chromatin remodeller Hrp1. The data presented
      here demonstrate that in fission yeast the SWIRM/PAO domain proteins Swm1 and
      Swm2 are associated in complexes that can remove methyl groups from lysine 9
      methylated histone H3. In vitro, we show that bacterially expressed Swm1 also
      possesses lysine 9 demethylase activity. In vivo, loss of Swm1 increases the
      global levels of both H3K9me2 and H3K4me2. A significant accumulation of H3K4me2
      is observed at genes that are up-regulated in a swm1 deletion strain. In
      addition, H3K9me2 accumulates at some genes known to be direct Swm1/2 targets
      that are down-regulated in the swm1Delta strain. The in vivo data indicate that
      Swm1 acts in concert with the HDAC Clr6 and the chromatin remodeller Hrp1 to
      repress gene expression. In addition, our in vitro analyses suggest that the H3K9
      demethylase activity requires an unidentified post-translational modification to
      allow it to act. Thus, our results highlight complex interactions between histone
      demethylase, deacetylase and chromatin remodelling activities in the regulation
      of gene expression.

PMID- 17440623
TI  - Changes in plasma prekallikrein activity, blood pressure, and left ventricular
      thickness in hypertensive and normotensive diabetic rats.
AB  - The present study examined plasma prekallikrein (PK) activity, left ventricular
      wall thickness (LVWT) and mean arterial blood pressure (BP) in diabetic and
      nondiabetic spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto
      (WKY) rats. The mean arterial BP was significantly raised (p < 0.01) in diabetic
      WKY rats and diabetic SHR when compared with their respective controls. The LVWT
      was significantly (p < 0.01) increased in diabetic WKY rats when compared with
      that in the control WKY rats. There was also an increase (p < 0.01) in the LVWT
      in the SHR and diabetic SHR when compared with that in the control WKY rats and
      diabetic WKY rats, respectively. The plasma PK activities were higher (p < 0.01)
      in diabetic WKY rats, SHR, and diabetic SHR against the mean value of control WKY
      rats. In this animal study, these findings suggest for the first time that higher
      plasma PK activity may serve as an indicator for predicting high BP and left
      ventricular hypertrophy in diabetic and hypertensive conditions. The possible
      significance of these observations is discussed.

PMID- 17440622
TI  - Epicutaneous immunization with type II collagen inhibits both onset and
      progression of chronic collagen-induced arthritis.
AB  - Epicutaneous immunization is a potential non-invasive technique for antigen
      specific immune-modulation. Topical application of protein antigens to barrier
      disrupted skin induces potent antigen-specific immunity with a strong Th2-bias.
      In this study, we investigate whether the autoimmune inflammatory response of
      chronic collagen-induced arthritis (CCIA) in DBA/1-TCR-beta Tg mice can be
      modified by epicutaneous immunization. We show that epicutaneous immunization
      with type II collagen (CII) inhibited development and progression of CCIA and,
      importantly, also ameliorated ongoing disease as indicated by clinical scores of
      disease severity, paw swelling and joints histology. Treated mice show reduced
      CII-driven T cell proliferation and IFN-gamma production, as well as
      significantly lower levels of CII-specific IgG2a serum antibodies. In contrast,
      CII-driven IL-4 production and IgE antibody levels were increased consistent with
      skewing of the CII response from Th1 to Th2 in treated mice. IL-4 production in
      treated mice was inversely correlated with disease severity. Moreover, T cells
      from treated mice inhibited proliferation and IFN-gamma production by T cells
      from CCIA mice, suggesting induction of regulatory T cells that actively inhibit
      effector responses in arthritic mice. The levels of CD4(+)CD25(+) T cells were
      however not increased following epicutaneous CII treatment. Together, these
      results suggest that epicutaneous immunization may be used as an immune
      modulating procedure to actively re-programme pathogenic Th1 responses, and could
      have potential as a novel specific and simple treatment for chronic autoimmune
      inflammatory diseases such as rheumatoid arthritis.

PMID- 17440624
TI  - Antibacterial properties of traditionally used Indian medicinal plants.
AB  - In search of broad-spectrum antibacterial activity from traditionally used Indian
      medicinal plants, 66 ethanolic plant extracts were screened against nine
      different bacteria. Of these, 39 extracts demonstrated activity against six or
      more test bacteria. Twelve extracts showing broad-spectrum activity were tested
      against specific multidrug-resistant (MDR) bacteria, methicillin-resistant
      Staphylococcus aureus (MRSA) and extended spectrum beta-lactamases (ESbetaL)
      producing enteric bacteria. In vitro efficacy was expressed in terms of minimum
      inhibitory concentration (MIC) values of plant extracts. MIC values ranged from
      0.32-7.5 mg/ml against MRSA and 0.31-6.25 mg/ml against ESbetaL-producing enteric
      bacteria. The overall activity against all groups of bacteria was found in order
      of Plumbago zeylanica > Hemidesmus indicus > Acorus calamus > Camellia sinensis >
      Terminalia chebula > Terminalia bellerica > Holarrhena antidysenterica > Lawsonia
      inermis > Mangifera indica > Punica granatum > Cichorium intybus and Delonix
      regia. In addition, these extracts showed synergistic interaction with
      tetracycline, chloramphenicol and ciprofloxacin against S. aureus and/or
      Escherichia coli. The ethanolic extracts of more than 12 plants were found
      nontoxic to sheep erythrocytes and nonmutagenic, determined by Ames test using
      Salmonella typhimurium test strains (TA 97a, TA 100, TA 102 and TA 104). Based on
      above properties, six plants-Plumbago zeylanica, Hemidesmus indicus, Acorus
      calamus, Punica granatum, Holarrhena antidysenterica and Delonix regia-were
      further subjected to fractionation-based study. Ethyl acetate, acetone and
      methanol fractions of more than six plants indicated that the active
      phytocompounds were distributed mainly into acetone and ethyl acetate fractions,
      whereas they were least prevalent in methanol fractions as evident from their
      antibacterial activity against MDR bacteria. Gram-positive and Gram-negative MDR
      bacteria are almost equally sensitive to these extracts/fractions, indicating
      their broad-spectrum nature. However, strain- and plant extract-dependent
      variations in the antibacterial activity were also evident. Time-kill assay with
      the most promising plant fraction Plumbago zeylanica (ethyl acetate fraction)
      demonstrated killing of test bacteria at the level lower than its MIC. Further,
      identification of active constituents in each fraction and their additive and
      synergistic interactions are needed to exploit them in evaluating efficacy and
      safety in vivo against MDR bacteria.

PMID- 17440625
TI  - Effect of fluoride intoxication on the levels of intestinal antioxidants studied
      in rats.
AB  - High concentration of fluorine is noxious to the health of humans and animals.
      Analysis of fluoride in water samples meant for human consumption in the Vellore
      District of Tamil Nadu, India, revealed its presence above the permissible limit
      (4.56 ppm). The present study was aimed to investigate the toxic effects of oral
      administration of the water sample that contains the highest fluoride content on
      the status of pathophysiological parameters and lipid peroxidation in
      experimental rats. A positive control group orally treated with 4.5 ppm of
      fluoride was also included in the study. The assay of pathophysiological enzymes
      and histological observations made on the stomach and intestinal tissue have
      revealed the toxic effects of fluoride intoxication. The observed increase in the
      levels of thiobarbituric acid reactive substances (TBARS) both in plasma and in
      intestinal epithelium, with a concomitant decrease in both enzymatic and
      nonenzymatic antioxidants in the plasma of experimental rats, revealed that the
      altered antioxidant status during fluoride intoxication may be due to increased
      free radical generation.

PMID- 17440626
TI  - Hypoglycemic and hypolipidemic effects of Aronia melanocarpa fruit juice in
      streptozotocin-induced diabetic rats.
AB  - Aronia melanocarpa fruit juice (AMFJ) is rich in phenolic antioxidants,
      especially flavonoids from the anthocyanin subclass. The aim of the present study
      was to investigate the influence of AMFJ on plasma glucose and lipids in diabetic
      rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (50
      mg/kg). AMFJ was applied by gavage at doses of 10 and 20 ml/kg for 6 weeks to
      normal and diabetic rats. Streptozotocin caused a significant elevation of plasma
      glucose by 141% and of plasma triglycerides (TG) by 64% in comparison with normal
      control rats and induced statistically insignificant elevations of total
      cholesterol and LDL-cholesterol and a reduction of HDL-cholesterol. Applied to
      normal rats, AMFJ did not influence plasma glucose and lipid levels. Applied to
      diabetic rats, AMFJ (10 and 20 ml/kg) significantly reduced plasma glucose by 44%
      and 42% and TG by 35% and 39%, respectively, to levels that did not significantly
      differ from those of the normal control rats and counteracted the influence of
      streptozotocin on total cholesterol, LDL-cholesterol and HDL-cholesterol. In
      conclusion, AMFJ significantly decreased the streptozotocin-induced abnormalities
      in blood glucose and TG in diabetic rats and might be useful in prevention and
      control of diabetes mellitus and diabetes-associated complications.

PMID- 17440627
TI  - A prospective study of adverse drug reactions in a dermatology department.
AB  - The objective of this study was to evaluate the clinical pattern and risk factors
      for adverse drug reactions (ADRs) in patients hospitalized in a specialized
      dermatology department. A prospective study was conducted in the Clinic of
      Dermatology and Venereology in Stara Zagora for a 5-year period. ADRs were
      classified by type, severity and causality. Case-causality was scored according
      to Naranjo et al. (1981). A total of 1041 admissions were analyzed. ADRs occurred
      in 147 patients. Cutaneous reactions represented the most common ADRs followed by
      endocrine/metabolic, cardiovascular and gastrointestinal disorders. The prevalent
      clinical patterns of cutaneous ADRs were exanthematous and urticarial. ADRs were
      almost evenly distributed as type A and type B reactions. Drug classes most
      frequently responsible for ADRs were glucocorticosteroids (GLCs) and
      antiinfective agents. The factors significantly associated with ADRs were the use
      of GLCs (OR 11.11; 95% CI 6.69-18.43), antiinfective agents (OR 1.48; 95% CI 1.04
      2.11) and older age. Patients hospitalized in a dermatology department may
      develop ADRs with multiorgan clinical presentation. The most important risk
      factors for ADRs in this sample of patients were the use of GLCs, antiinfective
      agents and older age. The study establishes a specific ADR risk profile of
      patients with dermatological disorders in a hospital setting.

PMID- 17440628
TI  - Clinical studies presented at major international meetings in 2006.

PMID- 17440629
TI  - Gateways to clinical trials.
AB  - Agomelatine, AGRO-100, AIDSVAX gp120 B/E, alfimeprase, aliskiren fumarate, ALVAC
      vCP1452, alvocidib hydrochloride, ambrisentan, AME-527, AN-0128, apadenoson, ARRY
      142886, asenapine maleate, axitinib, azimilide hydrochloride; Belimumab,
      bevacizumab, biolimus A9, BiovaxID, bryostatin 1; Cannabidiol, celgosivir, CG
      1940/CG-8711, CKD-501, collagen-PVP, CpG-10101, CTL-102, CTL-102/CB-1954; D-4F,
      darusentan, dexverapamil, DNA influenza vaccine, dronabinol/cannabidiol,
      dronedarone hydrochloride; Eculizumab, edodekin alfa, edotecarin, enzastaurin
      hydrochloride; Fingolimod hydrochloride; Golimumab; HBV-DNA vaccine, hyaluronic
      acid; I-131 ch-TNT-1/B, imatinib mesylate, inhaled insulin, ipilimumab, ispinesib
      mesylate, i.v. gamma-globulin; KU-59436; Lapaquistat; Mapatumumab, MC-1, MC
      1/lisinopril, mepolizumab; Nibentan, nilotinib, Nobori, NV1FGF; Ocrelizumab;
      Paclimer, pagoclone, paliperidone, PC-515, PHA-794428, phosphostim, PPI-2458,
      prasugrel, PTC-299; Renzapride hydrochloride, Reolysin, reslizumab, revaprazan
      hydrochloride, rivaroxaban, romidepsin, rubitecan, ruboxistaurin mesilate
      hydrate; Sapacitabine, SarCNU, ST-1859, sunitinib malate; Tanespimycin,
      temsirolimus, tgAAC-94, TGN-255, ticagrelor, tipifarnib, tolvaptan, tretazicar,
      TRU-015; Upgrade varicella vaccine, Ushercell; Vernakalant hydrochloride,
      verpasep caltespen, VNP-40101M, VRC-HIVADV014-00-VP, VRC-HIVDNA009-00-VP, VX-001;
      XL-647, XL-820, XL-880, XL-999.

PMID- 17440630
TI  - Histidine-lysine peptides as carriers of nucleic acids.
AB  - With their biodegradability and diversity of permutations, peptides have
      significant potential as carriers of nucleic acids. This review will focus on the
      sequence and branching patterns of peptide carriers composed primarily of
      histidines and lysines. While lysines within peptides are important for binding
      to the negatively charged phosphates, histidines are critical for endosomal lysis
      enabling nucleic acids to reach the cytosol. Histidine-lysine (HK) polymers by
      either covalent or ionic bonds with liposomes augment transfection compared to
      liposome carriers alone. More recently, we have examined peptides as sole
      carriers of nucleic acids because of their intrinsic advantages compared to the
      bipartite HK/liposome carriers. With a protocol change and addition of a
      histidine-rich tail, HK peptides as sole carriers were more effective than
      liposomes alone in several cell lines. While four-branched polymers with a
      primary repeating sequence pattern of -HHK- were more effective as carriers of
      plasmids, eight-branched polymers with a sequence pattern of -HHHK- were more
      effective as carriers of siRNA. Compared to polyethylenimine, HK carriers of
      siRNA and plasmids had reduced toxicity. When injected intravenously, HK polymers
      in complex with plasmids encoding antiangiogenic proteins significantly decreased
      tumor growth. Furthermore, modification of HK polymers with polyethylene glycol
      and vascular-specific ligands increased specificity of the polyplex to the tumor
      by more than 40-fold. Together with further development and insight on the
      structure of HK polyplexes, HK peptides may prove to be useful as carriers of
      different forms of nucleic acids both in vitro and in vivo.

PMID- 17440631
TI  - Radioimmunotherapy of non-Hodgkin's lymphoma: molecular targeting and novel
      agents.
AB  - In recent years monoclonal antibodies have played an important role in cancer
      therapy. This successful track is grosso modo based upon developments in the
      production of desired antibody molecules, the identification of suitable tumor
      antigens and the construction of chimeric and fully humanized antibodies.
      Especially in hematologic disorders, notably in non-Hodgkin's disease, the
      monoclonal antibody rituximab has proven to be of value in relapsed or refractory
      disease. Yet, to overcome the nonoptimal properties of this drug, especially in
      relation to the time to next therapy, radiolabeled immunoconjugates have been
      synthesized. For this purpose, the radionuclide yttrium-90 has been linked to the
      monoclonal antibody ibritumomab via the chelator tiuxetan. The most recent
      clinical results of this radiolabeled agent versus the nonradioactive drug
      treatment are reviewed in this paper. Furthermore, attention is paid to the
      monoclonal antibody tositumomab labeled with iodine-131, of which the first
      clinical results have become available most recently. This overview also mentions
      possibilities to increase the therapeutic efficacy of radionuclide
      immunoconjugates. This can be achieved by enhancing the targeting characteristics
      of the antibody and the use of alpha radiation-emitting radionuclides.

PMID- 17440632
TI  - Enrichment of a squamous carcinoma vaccine.
AB  - We describe a new vaccination strategy for squamous cell carcinoma. In a mouse
      model, the vaccine is prepared by transfer of unfractionated DNA-fragments (25
      kb) from KLN205 cells, a squamous carcinoma cell line (DBA/2 mouse origin [H
      2(d)]) into LM cells, a highly immunogenic mouse fibroblast cell line that
      expresses allogeneic major histocompatibility complex (MHC) class I-determinants
      (H-2(k)). The number of vaccine cells can then be expanded for multiple
      immunizations, as desired. As only a small proportion of the transfected cell
      population was expected to have incorporated DNA segments that included genes
      specifying antigens associated with the squamous carcinoma cells, we devised a
      novel strategy to enrich the vaccine for cells that induced immunity to the
      squamous carcinoma cells. Twenty-five percent of tumor-bearing mice treated by
      immunization with the vaccine appeared to have rejected the squamous carcinoma
      cells; they survived indefinitely (more than 70 days). The therapeutic benefits
      of the enriched vaccine could be further enhanced by treating the tumor-bearing
      mice with paclitaxel, a chemotherapeutic agent, followed by immunization with the
      enriched vaccine. Under these circumstances, 75% of mice with squamous carcinoma
      appeared to have rejected the squamous carcinoma cells. Toxic effects including
      the development of autoimmune disease were not detected in tumor-bearing mice
      receiving the combined therapy.

PMID- 17440633
TI  - The role of metabotropic glutamate receptors in drug reward, motivation and
      dependence.
AB  - Addiction to drugs of abuse is a disorder that involves dysfunctions in
      motivational processes. Both the primary rewarding effects of drugs, as well as
      the acquired motivational properties of stimuli associated with drug-seeking and 
      taking, contribute to the perpetuation of dependence on drugs of abuse.
      Metabotropic glutamate (mGlu) receptors, which mediate slow glutamate
      neurotransmission, are located throughout limbic and cortical brain sites
      implicated in drug addiction. Preclinical evidence suggests that mGlu receptors
      play a crucial role in regulating behavioral effects of drugs of abuse relevant
      to drug addiction. Specifically, antagonists at excitatory postsynaptic mGlu5
      receptors decrease drug self-administration without affecting motor behaviors,
      cognition or the reward value of natural rewards, while agonists at inhibitory
      presynaptic mGlu2/3 receptor agonists prevent reinstatement to drug-seeking and 
      taking after a period of abstinence. These findings have increased our
      understanding of the neuropathological processes associated with aspects of
      dependence on drugs of abuse and have provided new targets for pharmacological
      approaches to the treatment of dysfunctions in motivational processes
      characterizing the various phases of drug addiction.

PMID- 17440635
TI  - Stem cells: therapeutic present and future.
AB  - Ever since the first embryonic stem cells were isolated in the 1990s scientists
      and clinicians as well as the general public have followed the development of the
      field with great attention. As unspecialized cells capable of dividing, renewing
      and differentiating into specialized cells, stem cells hold great promise as a
      therapeutic strategy for many diseases, especially those of degenerative nature.
      In 2006, stem cells were actively investigated in preclinical and clinical
      settings to manage heart failure, amyotrophic lateral sclerosis, spinal cord
      injury, stroke, hematologic disorders, renal cell carcinoma, solid tumor cancer,
      Crohn's disease and cirrhosis, among other disorders. Likewise, biotech and
      pharmaceutical industry highlighted stem cells and associated products and
      technologies as useful tools for drug discovery that provide relevant clinical
      models and ensure efficacious transition of investigational compounds into
      preclinical testing.

PMID- 17440634
TI  - Chemopreventive promise of targeting the Nrf2 pathway.
AB  - The Kelch ECH associating protein 1-nuclear factor-E2-related factor 2
      antioxidant response element (Keap 1-Nrf2-ARE) signaling pathway regulates
      several protective mechanisms including expression of conjugating and
      antioxidative genes, antiinflammatory responses, the molecular chaperone/stress
      response system and the ubiquitin/proteasome system. The Nrf2-mediated response
      alters susceptibility to carcinogenesis, acute chemical toxicity, oxidative
      stress, asthma, acute inflammation, septic shock and neurodegenerative diseases
      such as Alzheimer's disease and Parkinson's disease. Studies using natural and
      synthetic chemical inducers that activate Nrf2 signaling have demonstrated
      protective efficacy in many animal models of disease. Conversely, studies in Nrf2
      disrupted mice indicate they exhibit increased sensitivity to many of these
      diseases. Thus, activation of Keap1-Nrf2-ARE signaling constitutes a broad
      protective response, making Nrf2 and its interacting partners important targets
      for chemoprevention. However, additional studies are needed to characterize Keap1
      Nrf2-ARE signaling in humans to further develop exceptionally potent activators
      of the pathway and further understand the potential consequences of altering this
      system.

PMID- 17440637
TI  - Molecule of the month: lisdexamfetamine mesilate.

PMID- 17440636
TI  - Chronicles in drug discovery.
AB  - Chronicles in Drug Discovery features special interest reports on advances in
      drug discovery. This month we highlight agents that target and deplete
      immunosuppressive regulatory T cells, which are produced by tumor cells to hinder
      innate immunity against, or chemotherapies targeting, tumor-associated antigens.
      Antiviral treatments for respiratory syncytial virus, a severe and prevalent
      infection in children, are limited due to their side effect profiles and cost.
      New strategies currently under clinical development include monoclonal
      antibodies, siRNAs, vaccines and oral small molecule inhibitors. Recent
      therapeutic lines for Huntington's disease include gene therapies that target the
      mutated human huntingtin gene or deliver neuroprotective growth factors and
      cellular transplantation in apoptotic regions of the brain. Finally, we highlight
      the antiinflammatory and antinociceptive properties of new compounds targeting
      the somatostatin receptor subtype sst4, which warrant further study for their
      potential application as clinical analgesics.

PMID- 17440638
TI  - Therapeutic approaches towards the treatment of gastroinstestinal disorders.
AB  - The Society for Medicines Research gathered an international panel of speakers
      and about 60 delegates for their symposium September 21, 2006, on Therapeutic
      Approaches Towards the Treatment of Gastroinstestinal Disorders, at the National
      Heart and Lung Institute, in London, U.K. The focus of the conference was to
      discuss therapeutic strategies taken towards the treatment of inflammatory bowel
      disease, acid related disorders and irritable bowel syndrome. Key note lectures
      addressed the development of tegaserod, a 5-HT(4) receptor agonist, for the
      treatment of constipation dominant irritable bowel syndrome (cIBS), the use of
      tumor necrosis factor alpha (TNFalpha) inhibitors in the treatment of chronic
      inflammatory diseases, including Crohn's disease, the development of effective
      inhibitors of gastric acid secretion, the role of alpha(4)beta(7) integrin in the
      development of Crohn's disease and ulcerative colitis, the parts played by the
      neuropeptides ghrelin and motilin in the control of gastrointestinal motility,
      and the role of bacteria in functional gastrointestinal disease.

PMID- 17440639
TI  - Contrast echocardiography in Canada: Canadian Cardiovascular Society/Canadian
      Society of Echocardiography position paper.
AB  - As an adjunct to transthoracic, transesophageal and stress echocardiography,
      contrast echocardiography (CE) improves the diagnostic accuracy of technically
      suboptimal studies when used in conjunction with harmonic imaging. Intravenous
      ultrasound contrast agents are indicated for left ventricular (LV) opacification
      and improvement of LV endocardial border delineation in patients with suboptimal
      acoustic windows. Demonstrated benefits of CE include improvement in the accuracy
      of LV measurements, regional wall motion assessment, evaluation of noncompaction
      cardiomyopathy, thrombus detection, Doppler signal enhancement and conjunctive
      use with stress echocardiography. Studies have shown the value of CE in the
      assessment and quantification of myocardial perfusion, and recent clinical trials
      have suggested a role for contrast perfusion imaging in the stratification of
      patients with suspected coronary artery disease. While it adds some time and cost
      to the echocardiographic study, CE frequently obviates the need for additional
      specialized, expensive and less accessible cardiac investigations, and allows for
      prompt and optimal subsequent patient management. Despite its proven advantages,
      CE is presently underused in Canada, and this situation will, unfortunately, not
      improve until several barriers to its use are overcome. Resolving these important
      hurdles is vital to the future of CE and to its eventual implementation into
      clinical practice of promising contrast-based diagnostic and therapeutic
      applications, including the assessment of perfusion by myocardial CE.

PMID- 17440640
TI  - Patterns of medical therapy in patients with peripheral artery disease in a
      tertiary care centre in Canada.
AB  - BACKGROUND: Patients with peripheral artery disease (PAD) of the lower
      extremities are among the highest risk vascular patients for fatal and nonfatal
      myocardial infarction and stroke, and have been traditionally undertreated from a
      medical perspective. Recent evidence suggests that the incidence of
      cardiovascular death, myocardial infarction and stroke can be substantially
      reduced among PAD patients if they are treated with antiplatelet therapy, 3
      hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), angiotensin
      converting enzyme inhibitors (ACEIs) and in some instances, beta-blockers.
      OBJECTIVES: To characterize practice patterns of drug therapy (antiplatelet,
      statin, ACEI and beta-blocker) among PAD patients admitted to a tertiary care
      hospital and to determine the 'care gap', defined as the proportion of patients
      who did not receive therapy among those who were eligible for it. DESIGN AND
      METHODS: Patients with PAD (International Classification of Diseases code 440.2)
      admitted to the Hamilton General Hospital (Hamilton, Ontario) from January 2001
      to January 2002 were considered for inclusion into the present study. Information
      was collected during hospitalization and by chart review. RESULTS: Data from 217
      patients were used. The mean (+/- SD) age of participants was 68.6+/-11.9 years,
      and 41% were women. The primary reason for admission to hospital was peripheral
      artery bypass surgery (67%). Of these patients, 79% were current smokers or had a
      prior history of tobacco use, 60% had at least two cardiovascular risk factors
      (hypertension, cholesterol, diabetes or smoking) and 45% had undergone prior
      peripheral artery bypass surgery, amputation or carotid endarterectomy. Three
      quarters of the patients had established coronary or cerebrovascular disease, or
      at least two cardiovascular risk factors. At the time of discharge, of those
      patients eligible for medical therapies, 16% did not receive antiplatelet or
      anticoagulant agents, 69% did not receive statins, 48% did not receive ACEIs and
      49% did not receive beta-blockers. CONCLUSIONS: Patients with PAD represent a
      high-risk group in which more than 75% have established coronary or
      cerebrovascular disease, or multiple cardiovascular risk factors. Although the
      use of antiplatelet agents is common, the use of statins, ACEIs and beta-blockers
      may be improved.

PMID- 17440641
TI  - Management of acute severe perioperative failure of cardiac allografts: a single
      centre experience with a review of the literature.
AB  - BACKGROUND: Early graft failure is associated with high mortality and is the main
      cause of death within the first 30 days after transplantation. The purpose of the
      present study was to examine the investigators' experience of severe
      perioperative acute graft failure and to review the literature. METHODS: Nine of
      385 cardiac transplants (2.3%) performed from 1984 through 2005 developed severe
      perioperative acute graft failure either in the operating room or within 24 h
      after cardiac transplantation. Four patients had primary graft failure, two had
      right heart failure secondary to pulmonary hypertension, one had hyperacute
      rejection, one had accelerated acute rejection and one possibly sustained a
      particulate coronary embolus intraoperatively. RESULTS: All except the two
      patients who had right heart failure secondary to pulmonary hypertension received
      mechanical circulatory support. Three patients were supported with total
      artificial hearts, two patients received a left ventricular assist device, one
      patient was supported with extracorporeal life support followed by a right
      ventricular assist device when the left ventricle recovered, and one patient was
      supported for several hours with cardiopulmonary bypass. Three patients were
      retransplanted after mechanical circulatory support, but only one survived. Only
      one of the nine patients (11%) survived; this patient was supported with a total
      artificial heart followed by retransplantation. CONCLUSION: The outcome of severe
      perioperative acute graft failure is very poor. Mechanical circulatory support
      and retransplantation are not as successful as in other situations. Due to the
      shortage of donors and poor outcomes, retransplantation for hyperacute rejection
      is not advisable.

PMID- 17440642
TI  - A study to assess the effects of a broad-spectrum immune modulatory therapy on
      mortality and morbidity in patients with chronic heart failure: the ACCLAIM trial
      rationale and design.
AB  - BACKGROUND: Evidence has accumulated regarding the importance of inflammatory
      mediators in the development and progression of heart failure (HF). Although
      targeted anticytokine treatment strategies, specifically antitumour necrosis
      factor-alpha, have yielded disappointing results, this may simply reflect the
      redundancy of the cytokine cascade and the fact that antitumour necrosis factor
      alpha therapies do not stimulate increased activity of the anti-inflammatory arm
      of the immune system. Ex vivo exposure of autologous blood to controlled
      oxidative stress and subsequent intramuscular administration is a device-based
      procedure shown in experimental studies to have a broad-spectrum effect on a
      number of immune mediators. These studies have demonstrated that this approach
      downregulates inflammatory cytokines, whereas several anti-inflammatory cytokines
      are increased. In a feasibility study of 73 patients with moderate to severe HF,
      active therapy (versus placebo) had a significant benefit on both mortality and
      hospitalization, and was not associated with adverse hemodynamic or metabolic
      effects. METHODS: The Advanced Chronic heart failure CLinical Assessment of
      Immune Modulation therapy (ACCLAIM) trial is a multicentre, randomized, double
      blind, placebo-controlled clinical trial of New York Heart Association functional
      class II to IV chronic HF patients with left ventricular ejection fraction of 30%
      or less. Enrolling approximately 2400 subjects at 177 sites, the primary end
      point of the study was the cumulative incidence (time to first event) of the
      combined end point of total mortality or hospitalization for cardiovascular
      causes. The study was completed in late 2005, when 701 primary end point events
      had occurred and all patients had been treated for six months. CONCLUSIONS: If
      the ACCLAIM trial confirms earlier results, this approach represents a novel
      nonpharmacological treatment for HF that targets a pathogenic mechanism
      contributing to progression of this syndrome not addressed by current therapies.

PMID- 17440643
TI  - Expedited blood pressure control with initial angiotensin II antagonist/diuretic
      therapy compared with stepped-care therapy in patients with ambulatory systolic
      hypertension.
AB  - OBJECTIVES: The present study investigated whether initiating therapy with a
      combination of losartan (L) and hydrochlorothiazide (HCTZ) allows for faster
      blood pressure (BP) control and fewer medications than the usual stepped-care
      approach in patients with stage 2 or 3 hypertension and ambulatory systolic
      hypertension. METHODS: Patients with a mean daytime systolic ambulatory BP (ABP)
      of 135 mmHg or higher were randomly assigned to receive L 50 mg plus HCTZ 12.5 mg
      titrated to L 100 mg plus HCTZ 25 mg versus HCTZ 12.5 mg plus atenolol 50 mg.
      Amlodipine 5 mg was then added, if needed, to achieve a BP goal of less than 130
      mmHg. Treatment titration was based on ABP. RESULTS: Significantly more patients
      randomly assigned to L/HCTZ (63.5%) than stepped-care (37.5%; P=0.008) achieved
      the primary end point (daytime systolic BP of less than 130 mmHg). Initial L/HCTZ
      induced significantly greater decreases in ABP during each 24 h period after six
      weeks of therapy. Although reductions in systolic and diastolic ABP were not
      statistically different at the end of the study, ABP reduction was significantly
      greater (P<0.001) with the L/HCTZ-based regimen. Twice as many patients in the
      L/HCTZ group achieved the goal ABP with no more than two drugs (30.0% versus
      14.7%; P=0.03). Moreover, tolerability was significantly better (P=0.006) in the
      L/HCTZ group, with a 40.0% incidence of adverse events, versus 65.6% in the
      stepped-care group. CONCLUSION: Initiating antihypertensive therapy with the
      combination of L/HCTZ in patients with stage 2 or 3 hypertension and ambulatory
      systolic hypertension reaches a target BP faster in a higher proportion of
      patients, with fewer adverse events and less need for a third drug regimen than
      the conventional stepped-care approach.

PMID- 17440645
TI  - A mitral-aortic intervalvular fibrosa false aneurysm in a patient without overt
      heart disease.
AB  - False aneurysms originating from mitral-aortic intervalvular fibrosa are
      clinically very rare. A 22-year-old male patient without overt heart disease was
      admitted to the cardiology department of the Gulhane Military Academy of
      Medicine, Ankara, Turkey, with a false aneurysm located between the left
      ventricular outflow tract and the anterior left atrium. The false aneurysm was
      repaired at the Department of Cardiovascular Surgery, and the patient was
      discharged 10 days after the surgery.

PMID- 17440644
TI  - Quality indicators for cardiovascular primary care.
AB  - BACKGROUND: The Canadian Cardiovascular Outcomes Research Team was established in
      2001 to improve the quality of cardiovascular care for Canadians. Initially,
      quality indicators (QIs) for hospital-based care for those with acute myocardial
      infarctions and congestive heart failure were developed and measured. Qualitative
      research on the acceptability of those indicators concluded that indicators were
      needed for ambulatory primary care practice, where the bulk of cardiovascular
      disease care occurs. OBJECTIVES: To systematically develop QIs for primary care
      practice for the primary prevention and chronic disease management of ischemic
      heart disease, hypertension, hyperlipidemia and heart failure. METHODS: A four
      stage modified Delphi approach was used and included a literature review of
      evidence-based practice guidelines and previously developed QIs; the development
      and circulation of a survey tool with proposed QIs, asking respondents to rate
      each indicator for validity, necessity to record and feasibility to collect; an
      in-person meeting of respondents to resolve rating and content discrepancies, and
      suggest additional QIs; and recirculation of the survey tool for rating of
      additional QIs. Participants from across Canada included family physicians,
      primary care nurses, an emergency room family physician and cardiologists.
      RESULTS: 31 QIs were agreed on, nine of which were for primary prevention and 22
      of which were for chronic disease management. CONCLUSIONS: A core set of QIs for
      ambulatory primary care practice has been developed as a tool for practitioners
      to evaluate the quality of cardiovascular disease care. While the participants
      rated the indicators as feasible to collect, the next step will be to conduct
      field validation.

PMID- 17440646
TI  - Totally endoscopic sequential arterial coronary artery bypass grafting on the
      beating heart.
AB  - A 50-year-old man was referred to the Department of Thoracic and Cardiovascular
      Surgery at the Johann Wolfgang-Goethe University (Frankfurt, Germany) with angina
      on exertion. An evaluation revealed critical stenosis involving the proximal
      portion of the left anterior descending artery and the first diagonal branch. The
      patient underwent successful sequential grafting of the left internal mammary
      artery to the left anterior descending artery and the diagonal branch using a
      totally endoscopic coronary artery bypass grafting technique on the beating heart
      with a new version of the da Vinci Surgical System (Intuitive Surgical, USA). To
      the authors' knowledge, this is the first report in literature to describe
      sequential arterial off-pump grafting of two anterior wall target vessels using a
      totally endoscopic technique on the beating heart.

PMID- 17440647
TI  - Human herpesvirus 6 subtype A-associated myocarditis with 'apical ballooning'.
AB  - A 67-year-old woman who presented with acute chest pain is reported. Three days
      before admission, she suffered from a flu-like infection. Coronary angiography
      showed no coronary stenosis. Ventriculography showed moderately reduced left
      ventricular function characterized by the so-called 'apical ballooning'.
      Endomyocardial biopsies and polymerase chain reaction analysis of the plasma
      revealed an acute infection with human herpesvirus 6 subtype A. Histological and
      immunohistochemical analyses revealed myocarditis with areas of interstitial
      macrophages and fibrosis. The present case report links, for the first time,
      myocarditis with a human herpesvirus 6 subtype A infection and the appearance of
      apical ballooning.

PMID- 17440648
TI  - Effect of shear stress on plaque rupture.

PMID- 17440649
TI  - How common is condom failure?

PMID- 17440650
TI  - Mid-level workers: high-level bungling?

PMID- 17440651
TI  - Altruism or perverse incentive?

PMID- 17440652
TI  - Medicines Control Council and registration backlog of antiretrovirals.

PMID- 17440653
TI  - Child abuse and our society.

PMID- 17440655
TI  - Salmonella typhi central nervous system infection.

PMID- 17440654
TI  - The South African Hypertension Guideline 2006 is evidence-based and not cost
      effective--a rebuttal.

PMID- 17440656
TI  - New focus urgent after Khomanani resuscitation.

PMID- 17440657
TI  - The loveLife-saving "ripple effect"--groundbreakers seed hopeful attitudes.

PMID- 17440658
TI  - Breastmilk banking regains vital expression.

PMID- 17440659
TI  - Asthma--is survival good enough?

PMID- 17440660
TI  - Fluconazole donation and outcomes assessment in cryptococcal meningitis.

PMID- 17440661
TI  - Journal clubs--knowledge sufficient for critical appraisal of the literature?

PMID- 17440662
TI  - Large-bowel obstruction as a result of traumatic diaphragmatic hernia.

PMID- 17440663
TI  - Tubal pregnancy beyond term.

PMID- 17440664
TI  - Perforated appendicitis--a rare cause of pneumoperitoneum.

PMID- 17440665
TI  - HIV incidence estimates are key to understanding the changing HIV epidemic in
      South Africa.

PMID- 17440666
TI  - Circumcision complications associated with the Plastibell device.

PMID- 17440668
TI  - One step forward, two steps back--requiring ministerial approval for all "non
      therapeutic" health research involving minors.
AB  - The new National Health Act has clarified that children may take part in "non
      therapeutic" research (NTR) and the age at which they may provide independent
      consent to such research, viz. at legal majority. However, the Act will require
      consent from the Minister of Health for all research classed as NTR and involving
      minors regardless of the level of risk. This requirement is overly broad. It will
      require that low-risk research without direct benefits, which might be adequately
      reviewed by an accredited research ethics committee (REC), must also be reviewed
      by the Minister. As it currently stands this requirement serves no plausible
      ethical purpose, will cause delays and discourage essential research on the needs
      of children, and may inspire researchers and RECs alike to "foil the system". We
      argue that in the long term there should be comprehensive law reform for child
      research. However, in the short term, amendments should be made to the Act to
      narrow the scope of this provision. The amendment should require ministerial
      consent for research that is currently not approvable by an REC in terms of
      national ethical guidelines, namely, research that does not hold out direct
      benefit but presents more than a minor increase over minimal risk. If our law
      reform recommendations are rejected, we favour the delegation of this task to
      RECs because, if they receive appropriate training, they should be competent to
      conduct it. We accept the disadvantages, namely that the same body will review
      protocols twice from slightly different perspectives and that certain categories
      of research will remain unapprovable.

PMID- 17440667
TI  - National HIV incidence measures--new insights into the South African epidemic.
AB  - BACKGROUND AND OBJECTIVES: Currently South Africa does not have national HIV
      incidence data based on laboratory testing of blood specimens. The 2005 South
      African national HIV household survey was analysed to generate national incidence
      estimates stratified by age, sex, race, province and locality type, to compare
      the HIV incidence and HIV prevalence profiles by sex, and to examine the
      relationship between HIV prevalence, HIV incidence and associated risk factors.
      METHOD: The detection of recent infections was performed on confirmed HIV
      positive samples, using the BED capture enzyme immunoassay optimised for dried
      blood spot (DBS) specimens. BED HIV incidence calculations applied adjustment
      procedures that were recently revised and approved by the Centers for Disease
      Control and Prevention for subtype C blood specimens. RESULTS: HIV incidence in
      the study population aged 2 years and older was 1.4% per year, with 571,000 new
      HIV infections estimated for 2005. An HIV incidence rate of 2.4% was recorded for
      the age group 15-49 years. The incidence of HIV among females peaked in the 20-29
      year age group at 5.6%, more than six times the incidence found in 20-29-year-old
      males (0.9%). Among youth aged 15-24 years, females account for 90% of the recent
      HIV infections. Non-condom use among youth, current pregnancy and widowhood were
      the socio-behavioural factors associated with the highest HIV incidence rates.
      CONCLUSIONS: The HIV incidence estimates reflect the underlying transmission
      dynamics that are currently at work in South Africa. The findings suggest that
      the current prevention campaigns are not having the desired impact, particularly
      among young women.

PMID- 17440669
TI  - Cervical spine injury outcome--a review of 101 cases treated in a tertiary
      referral unit.
AB  - Cervical spinal cord injury (SCI) is a devastating event for the patient and
      family. It has a huge impact on society because of the intensive resources
      required to manage the patient in both the acute and rehabilitation phases. Given
      the resource-limited setting in South Africa, questions are often raised
      regarding whether the outcome of this group of patients justifies the expense of
      their care. However local data have not been available to date. OBJECTIVE: To
      evaluate the mortality, morbidity and functional outcome of cervical SCI patients
      in the South African environment. MATERIAL AND METHODS: All cervical SCI patients
      managed in the acute spinal cord injury unit at Groote Schuur Hospital over a 12
      month period were included. Epidemiological data, management, complications,
      neurological status and change were assessed. Those referred for rehabilitation
      were followed up in terms of mortality and ambulation status. RESULTS: There were
      101 patients, with an average age of 34.7 years. Motor vehicle accidents were the
      commonest cause of injury, with violence contributing 21%. Fifty-nine patients
      required referral to a rehabilitation unit. Of these, 18 were functional walkers,
      and only 6 were care-dependent. By 1 year post injury all but 1 patient had been
      discharged from the health service. Fourteen patients died; in half of these
      cases injury was at C5 level and above. CONCLUSION: Despite cervical SCI being a
      devastating event, aggressive early intervention yields a better-than-expected 1
      year survival rate. Associated problems, such as pressure sores, remain a major
      problem both for the patient and in terms of health care costs. It is difficult
      to predict prognosis on presentation because of spinal shock. It is recommended
      that all patients initially be treated aggressively, with exit strategies in
      place once all the information is available and a confident assessment of poor
      prognosis can be made.

PMID- 17440671
TI  - Effects of the Tobacco Products Control Amendment Act of 1999 on restaurant
      revenues in South Africa--a survey approach.
AB  - OBJECTIVE: To investigate the impact of the restrictions on smoking in indoor
      public places on the financial situation of the hospitality industry. METHODS: A
      telephone survey was undertaken of 1011 restaurants, selected by searching public
      access Internet databases. RESULTS: Fifty per cent of surveyed restaurants spent
      an average of R67 000 (median of R25 000) to comply with the clean indoor air
      legislation. The capital cost for the remaining 50% of restaurants was zero. The
      impact on restaurant revenues was limited: 59% of restaurants reported no change
      in revenue, 22% an increase and 19% a decrease as a result of the legislation.
      Franchised restaurants experienced a net gain in revenue (34% reporting an
      increase, 16% reporting a decrease, and 50% reporting no change), although on
      average they incurred more costs to comply with the legislation than independent
      restaurants. On average, independent restaurants reported a decrease in their
      revenues as a result of the legislation (21% reporting a decrease, 13% reporting
      an increase, and 66% reporting no change). Ninety-two per cent of respondents
      believed that their restaurants complied with the legislation. The new smoking
      policies have been well accepted by nonsmokers (nearly 100%) and smokers (87%)
      alike. CONCLUSION: Despite the hospitality and tobacco industries' claim that the
      law restricting smoking in restaurants would have very detrimental financial
      consequences, the retrospective evidence does not support this.

PMID- 17440672
TI  - Hydrostatic pulmonary edema: high-resolution computed tomography aspects.
AB  - OBJECTIVE: This study aimed to use high-resolution computed tomography scans of
      the chest to characterize the principal alterations occurring in cases of
      hydrostatic pulmonary edema. METHODS: A retrospective analysis was made of the
      tomography scans of 15 patients presenting clinical profiles of hydrostatic
      pulmonary edema. The cases were divided into five groups by etiology: congestive
      heart failure (n = 7); acute mitral valve disease (n = 2); acute myocardial
      infarction (n = 2); myocarditis (n = 2); and fibrosing mediastinitis (n = 2).
      RESULTS: The principal findings in the cases of hydrostatic pulmonary edema were
      ground-glass opacities (in 100%), interlobular septal thickening (in 100%),
      pleural effusion (in 87%) and peribronchovascular interstitial thickening (in
      80%). Other, less common, findings were increased blood vessel diameter,
      consolidations and air-space nodules. CONCLUSION: The predominant pattern found
      in the patients studied was that of ground-glass opacities accompanied by
      interlobular septal thickening (mosaic attenuation pattern) and bilateral
      (predominantly right-sided) pleural effusion.

PMID- 17440673
TI  - Uptake and translocation of heavy metals in salt marsh sediments by Spartina
      patens.

PMID- 17440674
TI  - Prediction of bone loss using biochemical markers of bone turnover.
AB  - The association between baseline levels of eleven bone turnover markers and 5
      year rate of bone density change was prospectively studied in a population-based
      sample of 601 75-year-old women. Several bone formation and resorption markers as
      well as urinary osteocalcin were modestly correlated to rate of bone density
      change. INTRODUCTION: Prediction of bone loss by bone turnover markers (BTMs) has
      been investigated with conflicting results. There is limited information in the
      elderly. METHODS: Eleven bone turnover markers were analyzed in 75-year old women
      in the OPRA study (n = 601) and compared to the 5-year change of areal bone
      mineral density (aBMD) in seven skeletal regions. RESULTS: Annual aBMD change
      varied between +0.4% (spine) and -2.0% (femoral neck). Significant associations
      (p < 0.01) were found for four different serum osteocalcins (S-OCs) (standardized
      regression coefficient -0.20 to -0.22), urinary deoxypyridinoline (-0.19), serum
      TRACP5b (-0.19), serum CTX-I (-0.21), two of the three urinary osteocalcins (U
      OCs) (-0.16) and aBMD change of the leg region (derived from the total body
      measurement). After adjustment for baseline aBMD, associations were found for all
      S-OCs (-0.11 to -0.16), two of the three U-OCs (-0.14 to -0.16) and aBMD change
      at the total hip, and for three of the four S-OCs (-0.14 to -0.15), S-TRACP5b (
      0.11), two of the three U-OCs (-0.14 to -0.15) and aBMD change at the femoral
      neck. There were no significant results concerning aBMD change at the spine.
      CONCLUSION: This study indicates that BTMs are correlated with aBMD loss in some
      skeletal regions in elderly women.

PMID- 17440675
TI  - Incidence of second hip fractures. A population-based study.
AB  - We studied the incidence of second hip fractures and medication use among the
      patients with sequential hip fractures. This study shows that the incidence rate
      of second hip fractures is higher than that of the first hip fractures.
      Improvement in osteoporosis care and a more critical policy for prescription of
      psychotropic drugs are needed. INTRODUCTION: This study had two goals: (1) to
      determine incidence of second hip fractures; (2) to describe changes in
      pharmacotherapy between first and second hip fractures, especially the use of
      those psychotropics which increase the risk of falling and also pharmacotherapy
      for osteoporosis. METHODS: The residents of Central Finland Health Care District
      who had sustained a hip fracture in 2002-2003 were followed up for subsequent hip
      fractures until 2006. Hip fracture patients were identified and clinical data
      were obtained by using hospital registers and medical records. RESULTS: Five
      hundred and one persons aged >or= 60 years suffered their first hip fracture in
      2002-2003. During the follow-up of 936 person-years, 34 second hip fractures
      occurred. The cumulative incidence of second hip fractures was 5.08% (95% CI:
      3.30 to 7.78) at one year, and 8.11% (95% CI: 5.73 to 11.43) at two years after
      the first fracture. The second part of this study investigated 75 patients with
      two non-contemporaneous hip fractures. Between the first and second fractures,
      the number of psychotropic drug users rose from 27 (36%) to 44 (59%). At the time
      of second hip fracture, osteoporosis had been diagnosed in 17 (23%) patients
      only. Twelve (16%) patients used bisphosphonates or calcitonin, 15 (20%) used
      calcium and 9 (12%) vitamin D supplements. CONCLUSIONS: There is a high incidence
      of second hip fractures. Secondary prevention of hip fractures needs to be
      improved. In addition to adequate treatment for osteoporosis, more attention
      should be directed toward appropriate use of psychotropic drugs.

PMID- 17440677
TI  - Incidence and significance of the JAK2 V617F mutation in patients with chronic
      myeloproliferative disorders.
AB  - BACKGROUND: The chronic myeloproliferative disorders (MPD) are clonal
      haemopoietic stem cell disorders. AIMS: The incidence of JAK2 V617F mutation was
      sought in a population of patients with MPD. METHODS: The JAK2 V617 mutation
      status was determined in 79 patients with known MPD and 59 patients with features
      suggestive of MPD. RESULTS: The mutation was found in patients with polycythaemia
      vera, essential thrombocythaemia, idiopathic myelofibrosis and in patients with
      other chronic myeloproliferative disorders. Eight JAK2 V617F positive cases were
      identified amongst those patients with features suggestive of MPD. CONCLUSIONS:
      The incidence of the JAK2 V617F mutation in MPD patients is similar to that
      reported by other groups. The assay confirmed and refined the diagnosis of
      several patients with features indicative of MPD. We suggest screening for this
      mutation in all patients with known and suspected MPD as identification is
      valuable in classification and is a potential target for signal transduction
      therapy.

PMID- 17440678
TI  - Radiological study of the knee joint line position measured from the fibular head
      and proximal tibial landmarks.
AB  - Restoring the joint line level is one of the surgical challenges during revision
      of total knee arthroplasty. The position of the tibial surface is commonly
      estimated by its distance to the apex of fibular head, but no study evaluating
      this distance accurately has been published yet. The purpose of this work was to
      study the distance between the knee joint line and the apex of the fibular head
      and the proximal tibia, particularly the tibial tuberosity. Variability with
      clinical data and relations with other local measurements have been evaluated on
      knee radiographs (an antero-posterior view, a medio-lateral view and an
      anteroposterior full length view) of 100 subjects (125 knees). Results showed no
      correlation between the joint line-fibular head apex distance and any clinical
      data of the patients, or any other performed measurements. Relations between
      tibial measurements and the sexe or the height of the subjects were noted.
      Besides, the review of the 25 bilateral cases did not show statistically
      significant side difference but the descriptive analysis showed too large
      discrepancies for the joint line-fibular head apex distance to be used as a
      landmark. We conclude that the fibular head apex cannot be used as a morphologic
      landmark to determine the knee joint line position. Its interest in clinical and
      surgical practice must be discussed.

PMID- 17440676
TI  - First meeting on bone quality, Abbaye des Vaux de Cernay, France, 15-16 June
      2006: Bone architecture.

PMID- 17440679
TI  - The innate immunity of the central nervous system in chronic pain: the role of
      Toll-like receptors.
AB  - Toll-like receptors (TLRs) are a family of pattern recognition receptors that
      mediate innate immune responses to stimuli from pathogens or endogenous signals.
      Under various pathological conditions, the central nervous system (CNS) mounts a
      well-organized innate immune response, in which glial cells, in particular
      microglia, are activated. Further, the innate immune system has emerged as a
      promising target for therapeutic control of development and persistence of
      chronic pain. Especially, microglial cells respond to peripheral and central
      infection, injury, and other stressor signals arriving at the CNS and initiate a
      CNS immune activation that might contribute to chronic pain facilitation. In the
      orchestration of this limited immune reaction, TLRs on microglia appear to be
      most relevant in triggering and tailoring microglial activation, which might be a
      driving force of chronic pain. New therapeutic approaches targeting the CNS
      innate immune system may achieve the essential pharmacological control of chronic
      pain.

PMID- 17440681
TI  - Pharmacological profiling of novel non-COX-inhibiting indole-pyran analogues of
      etodolac reveals high solid tumour activity of SDX-308 in vitro.
AB  - SDX-308 and SDX-309 are potent indole-pyran analogues of SDX-101 (R-etodolac)
      which has anti-tumour activity unrelated to cyclooxygenase-2 inhibition. Their
      cytotoxic activity was further studied herein using a well-characterized human
      tumour cell-line panel containing ten cell lines, as well as in 58 primary tumour
      cell samples from a variety of diagnoses. The indole-pyran analogues of SDX-101
      were in general considerably more active in both cancer cell lines and primary
      tumour samples. Low cross-reactivity with standard agents was observed,
      indicating a unique mechanism of action. No apparent influence on efficacy was
      observed via classical mechanisms of multidrug-resistance. SDX-101 and SDX-309
      showed higher relative activity in haematological compared to solid tumour
      samples, while SDX-308 had pronounced solid-tumour activity. High SDX-308
      cytotoxic efficacy was observed in non-small cell lung cancer, renal cancer and
      ovarian cancer samples, and also in chronic lymphocytic leukaemia. In conclusion,
      the indole-pyran analogues showed a favourable pharmacological profile and
      represent a potentially important new class of drugs for cancer treatment.

PMID- 17440680
TI  - Viral capsids: mechanical characteristics, genome packaging and delivery
      mechanisms.
AB  - The main functions of viral capsids are to protect, transport and deliver their
      genome. The mechanical properties of capsids are supposed to be adapted to these
      tasks. Bacteriophage capsids also need to withstand the high pressures the DNA is
      exerting onto it as a result of the DNA packaging and its consequent confinement
      within the capsid. It is proposed that this pressure helps driving the genome
      into the host, but other mechanisms also seem to play an important role in
      ejection. DNA packaging and ejection strategies are obviously dependent on the
      mechanical properties of the capsid. This review focuses on the mechanical
      properties of viral capsids in general and the elucidation of the biophysical
      aspects of genome packaging mechanisms and genome delivery processes of double
      stranded DNA bacteriophages in particular.

PMID- 17440682
TI  - Erlotinib and vinorelbine in advanced malignant solid tumors: a phase I study.
AB  - BACKGROUND: Erlotinib is an oral epidermal growth factor receptor tyrosine kinase
      inhibitor (EGFR TKI). Vinorelbine, a vinca alkaloid, interferes with microtubule
      assembly inhibiting mitosis during metaphase. Both drugs are commonly used as
      single agents in the treatment of advanced non small cell lung cancer (NSCLC).
      Given their efficacy in NSCLC and their non-overlapping toxicity profile, we
      conducted a phase I study of erlotinib and vinorelbine to establish the
      feasibility and safety of the combination and to determine the maximum tolerated
      dose (MTD). PATIENTS AND METHODS: Patients with advanced solid tumors were
      treated with vinorelbine intravenously on day 1 and 8 and erlotinib orally daily
      on a 21 day schedule. The dose levels of vinorelbine/erlotinib were 25
      mg/m(2)/100 mg, 25/150 and 30/150. RESULTS: Sixteen patients were enrolled. Five
      patients were chemo-naive; 11 had one prior therapy. The majority of patients had
      NSCLC (n = 7). Dose limiting toxicities included febrile neutropenia (4 patients)
      and grade 5 infection (1 patient). Non-hematologic grade 3/4 toxicities included
      diarrhea, hypokalemia, infection, dyspnea and mucositis. Of 12 patients
      assessable for radiologic response, there were no objective responses; eight had
      stable disease. CONCLUSIONS: (1) The MTD was vinorelbine 25 mg/m2 day 1 and 8
      with erlotinib 100 mg/day every 21 days. (2) The combination was associated with
      high rate of febrile neutropenia (25%). (3) Due to subsequent data demonstrating
      a lack of efficacy of erlotinib in combination with platinum doublets in advanced
      NSCLC, this combination has not been explored further.

PMID- 17440683
TI  - Hypoxia and radiotherapy: opportunities for improved outcomes in cancer
      treatment.
AB  - A large body of clinical evidence exists to suggest that tumor hypoxia negatively
      impacts radiotherapy. As a result, there has been longstanding active research
      into novel methods of improving tumor oxygenation, targeting hypoxic tumor cells,
      and otherwise modulating the effect hypoxia has on how tumors respond to
      radiation. Over time, as more has been learned about the many ways hypoxia
      affects tumors, our understanding of the mechanisms connecting hypoxia to
      radiosensitivity has become increasingly broad and complicated. This has opened
      up new potential avenues for interrupting hypoxia's negative effects on tumor
      radiosensitivity. Here, we will review what is currently known about the spectrum
      of influence hypoxia has over the way tumors respond to radiation. Particular
      focus will be placed on recent discoveries suggesting that hypoxia-inducible
      factor-1 (HIF-1), a transcription factor that upregulates its target genes under
      hypoxic conditions, plays a major role in determining tumor radiosensitivity. HIF
      1 and/or its target genes may represent therapeutic targets which could be
      manipulated to influence hypoxia's impact on tumor radiosensitivity.

PMID- 17440684
TI  - Hypoxia in cancer: significance and impact on clinical outcome.
AB  - Hypoxia, a characteristic feature of locally advanced solid tumors, has emerged
      as a pivotal factor of the tumor (patho-)physiome since it can promote tumor
      progression and resistance to therapy. Hypoxia represents a "Janus face" in tumor
      biology because (a) it is associated with restrained proliferation,
      differentiation, necrosis or apoptosis, and (b) it can also lead to the
      development of an aggressive phenotype. Independent of standard prognostic
      factors, such as tumor stage and nodal status, hypoxia has been suggested as an
      adverse prognostic factor for patient outcome. Studies of tumor hypoxia involving
      the direct assessment of the oxygenation status have suggested worse disease-free
      survival for patients with hypoxic cervical cancers or soft tissue sarcomas. In
      head & neck cancers the studies suggest that hypoxia is prognostic for survival
      and local control. Technical limitations of the direct O(2) sensing technique
      have prompted the use of surrogate markers for tumor hypoxia, such as hypoxia
      related endogenous proteins (e.g., HIF-1alpha, GLUT-1, CA IX) or exogenous
      bioreductive drugs. In many - albeit not in all - studies endogenous markers
      showed prognostic significance for patient outcome. The prognostic relevance of
      exogenous markers, however, appears to be limited. Noninvasive assessment of
      hypoxia using imaging techniques can be achieved with PET or SPECT detection of
      radiolabeled tracers or with MRI techniques (e.g., BOLD). Clinical experience
      with these methods regarding patient prognosis is so far only limited. In the
      clinical studies performed up until now, the lack of standardized treatment
      protocols, inconsistencies of the endpoints characterizing the oxygenation status
      and methodological differences (e.g., different immunohistochemical staining
      procedures) may compromise the power of the prognostic parameter used.

PMID- 17440685
TI  - The effect of povidone iodine flush versus drops on conjunctival colonization
      before intravitreal injections.
AB  - BACKGROUND: To determine the most effective method of applying povidone iodine 5%
      to decrease conjunctival colonization before intravitreal injections. METHODS:
      Twenty-eight patients from two tertiary care centers undergoing intravitreal
      injection for diffuse diabetic macular edema, exudative age-related macular
      degeneration, venous occlusive disease, or refractory pseudophakic cystoid
      macular edema were prospectively randomized to two study arms. One arm received 2
      3 drops of 5% povidone iodine (drops group) and the second received a 10 ml flush
      of the same solution (flush group). The inferior conjunctival fornix was cultured
      before and after antiseptic technique was performed in all patients. Three
      culture media, thioglycollate broth, chocolate agar and blood agar, were used for
      each sample. RESULTS: Each study group had 14 patients. Prior to antisepsis, 22
      of the 28 (78.6%) subjects had positive conjunctival cultures. 16 and 14
      bacterial organisms were isolated in the first and second groups, respectively.
      After using 2-3 drops of 5% povidone iodine in the first study arm of patients,
      three of 16 (18.7% reduction) bacterial organisms were no longer isolated in
      thioglycollate broth media. With flush irrigation of 10 ml of 5% povidone iodine,
      seven of 14 (50% reduction) bacterial organisms were no longer isolated (P-value
      0.07) in broth media. No difference in reduction of bacterial colonization was
      found on plated media (chocolate agar and blood agar). CONCLUSIONS: Irrigating
      the conjunctival fornix with 5% povidone iodine results in greater reduction of
      bacterial colonization compared with drop application of the same solution. Flush
      irrigation may provide better protection against the risk of endophthalmitis with
      intravitreal injections.

PMID- 17440686
TI  - Biopsy techniques and yields in diagnosing primary intraocular lymphoma.
AB  - A review of current biopsy techniques that are used in obtaining specimens from
      which to make a diagnosis of primary intraocular lymphoma (PIOL) is presented.
      Methods for obtaining and subsequently testing vitrectomy specimens are
      discussed. In addition, the yields of external and internal approaches for
      obtaining chorioretinal tissue, and diagnostic vitrectomies, are reviewed.

PMID- 17440687
TI  - Kinetics and metabolic behavior of a composite culture of Kloeckera apiculata and
      Saccharomyces cerevisiae wine related strains.
AB  - The kinetics and metabolic behavior of Kloeckera apiculata mc1 and Saccharomyces
      cerevisiae mc2 in composite culture was investigated. K. apiculata showed a
      higher viability through the fermentation; however the maximum cell density of
      both yeasts decreased. This behavior was not due to ethanol concentration, killer
      toxins production or competition for assimilable nitrogenous compounds between
      both yeasts. Despite the consistent production of secondary products by single
      culture of K. apiculata, an increase of these compounds was not observed in mixed
      culture. These results contribute to a better understanding of the behavior of
      non-Saccharomyces yeasts and their potential application in the wine industry.

PMID- 17440688
TI  - Variations of ganglioside biosynthetic pathways in the phenotype conversion from
      myofibroblasts to lipocytes in murine hepatic stellate cell line.
AB  - GRX cell line represents hepatic stellate cell and can be transformed from an
      actively proliferation myofibroblast phenotype into a quiescent fat-storing
      lipocyte phenotype. Both express the same gangliosides (GM3, GM2, GM1 and GD1a),
      which are resolved as doublets on HPTLC. Upper/lower band ratio is increased in
      lipocyte-like cells and the upper band is composed by ceramides with long-chain
      fatty acids. This study evaluated the contribution of de novo synthesis,
      sphingosine and Golgi recycling pathways on ganglioside biosynthesis, in both
      phenotypes. Cells were preincubated with 5 mM beta-chloroalanine (SPT: serine
      palmitoyltransferase inhibitor) or with 25 muM fumonisin B1 (ceramide synthase
      inhibitor) and then radiolabeled with [U-(14)C]galactose in the continued
      presence of inhibitors. Gangliosides were extracted, purified and analyzed by
      HPTLC. In myofibroblast-like cells, simple gangliosides use the de novo pathway
      while complex gangliosides are mainly synthesized by recycling pathways. In
      lipocyte-like cells, de novo pathway has a lesser contribution and this is in
      agreement with the lower activity of the committed enzyme of sphingolipid
      synthesis (SPT) detected in this phenotype. SPT mRNA has an identical expression
      in both phenotypes. It was also observed that gangliosides doublets from
      myofibroblast-like cells have the same distribution between triton soluble and
      insoluble fractions (upper band > lower band) while the gangliosides doublets
      from lipocyte-like cells show an inversion in the insoluble fraction (lower band
      > upper band) in comparison to soluble fraction. These results indicate that
      myofibroblast- and lipocyte-like cells have important differences between the
      glycosphingolipid biosynthetic pathways, which could contribute with the
      respective glycosphingolipid-enriched membrane microdomain's composition.

PMID- 17440689
TI  - A novel mutation, Ser159Pro in the NeuroD1/BETA2 gene contributes to the
      development of diabetes in a Chinese potential MODY family.
AB  - OBJECTIVES: During examining the prevalence of mutations in NeuroD1/BETA2 gene in
      Chinese early-onset type 2 diabetic probands, a novel missense mutation,
      Ser159Pro in a potential MODY family was identified. To investigate the role of
      the mutation in early-onset diabetes, we studied its transcriptional activity on
      human insulin gene and clinical characteristics of the family with the mutation.
      METHODS: Bi-directional sequencing of NeuroD1/BETA2 was performed in 85 early
      onset type 2 diabetic probands without mutations in HNF4alpha, glucokinase,
      HNF1alpha, IPF-1 and HNF1beta genes, 95 late-onset type 2 diabetics with strong
      diabetic history and 87 non-diabetic control subjects. The function of the
      Ser159Pro to the transcription of a human insulin promotor-linked luciferase
      reporter gene in rat INS-1 cells was tested using Dual-Luciferase Reporter Assay
      System. Clinical phenotypes of the family with the Ser159Pro mutation were
      examined and analyzed. RESULTS: A novel mutation, Ser159Pro were found in a 27
      years-old proband with both parents had diabetes. The mutation was transmitted in
      the heterozygous state and co-segregated with diabetes in four out of five
      carriers from the paternal side. Expect for the proband, all of other members
      with this mutation in the family, however, were diagnosed with diabetes after 50
      years-old. The functional study showed that the mutant protein exhibited a 25%
      reduction in transcriptional activity of insulin gene when compared with the wild
      type. CONCLUSIONS: These results suggest that the novel Ser159Pro mutation in the
      NeuroD1/BETA2 gene contributes to the development of diabetes in a Chinese
      potential MODY family.

PMID- 17440690
TI  - Pattern expression of glycan residues in AZT-treated K562 cells analyzed by
      lectin cytochemistry.
AB  - The present paper shows that human chronic myeloid (K562) cells exposed 3 h to 20
      microM 3'-azido-3'-deoxythymidine (AZT) exhibit marked variations of the
      oligosaccharide moiety of glycoconjugates. These changes were analyzed by
      confocal fluorescence microscopy, upon incubation of control and AZT-treated
      cells with biotin-lectin conjugates to visualize cell surface glycans or total
      glycans after cells permeabilization. In addition, cell fluorescence distribution
      of the biotinylated lectins, localized with streptavidin conjugates labeled with
      Alexa Fluor 488, was analyzed by flow cytometry. The results obtained show
      significant variations on the expression/distribution of membrane surface glycans
      as detected by both WGA and SNA, two lectins that recognize primarily cellular
      internal membrane glycolipids. A further interesting result was the significant
      increase of N-acetylglucosamine linked glycans localized either at the cell
      surface or intracellularly but only in K562 cells exposed to AZT. On the whole,
      our data demonstrate that AZT alters both lipid and N-linked glycosylations thus
      confirming previous observations, from our laboratory and from other Authors,
      that the drug impair the nucleotide-sugar import in the Golgi's lumen. AZT does
      also alter the O-linked glycosylations that occur in the Golgi complex since
      these reactions require the incorporation of sialic acid, GlcNAc and GalNAc all
      of which are sensitive to the drug.

PMID- 17440691
TI  - Evaluation of normal brain development by prenatal MR imaging.
AB  - PURPOSE: The aim of this study was to describe the normal pattern of development
      and maturation of the foetal brain with respect to gestational age as assessed
      with magnetic resonance imaging (MRI) and to provide an overview of the
      possibilities of the technique. MATERIALS AND METHODS: Foetal cerebral MRI was
      performed on 56 pregnant women between 19 and 37 weeks of gestation. Half-Fourier
      single-shot turbo spin-echo (HASTE), true fast imaging with steady precession
      (FISP), T1-weighted fast low angle shot (FLASH) two-dimensional (2D) and
      diffusion-weighted (DW) sequences with apparent diffusion coefficient (ADC) were
      obtained. Biometric parameters and developmental areas of the cerebral cortex
      were correlated to gestational age by using the Spearman rank correlation test.
      RESULT: We found a negative correlation between the germinal matrix/biparietal
      diameter ratio and gestational age and a positive correlation between the
      germinal and cortical matrix when expressed as external intraocular diameter
      ratio (R=0.452, p=0.02). The cortical mantle was correlated with biometric
      parameters, such as the biparietal diameter and the frontooccipital diameter, and
      with gestational age. The interhemispheric fissure, the parietooccipital fissure
      and the sylvian fissure were detectable by the 22nd week. In the grey matter, the
      mean ADC values varied from 1.76 x 10(-3) mm(2)/s (at week 19) to 0.89 x 10(-3)
      mm(2)/s (at week 37), whereas in the white matter, the values varied from 2.03 x
      10(-3) mm(2)/s (at week 19) to 1.25 x 10(-3) mm(2)/s (at week 37). CONCLUSIONS:
      MRI provides a reliable valuation of brain maturation during pregnancy.

PMID- 17440692
TI  - CT angiography versus colour-Doppler US in acute dissection of the vertebral
      artery.
AB  - PURPOSE: Conventional digital subtraction angiography (DSA) still represents the
      criterion standard for the diagnosis of vertebral artery dissection (VAD), but
      the main drawbacks of this technique include invasiveness, patient discomfort and
      risk of complications. We evaluated the potential of multidetector computed
      tomography angiography (CTA) as a noninvasive tool providing high-resolution
      images of the arterial lumen and wall by comparing the diagnostic accuracy of CTA
      and colour-Doppler ultrasonography (CDUS) in detecting acute VAD. MATERIALS AND
      METHODS: We retrospectively reviewed 15 cases of VAD in 15 patients (five men and
      ten women, age range 28-58 years) who came to our attention between August 2001
      and September 2005. The diagnosis was made on the basis of appropriate clinical
      presentation, absence of atherosclerotic disease in the cerebrovascular
      circulation and evidence of distinctive CT features, which were subsequently
      confirmed by conventional angiography used as reference standard. All patients
      with a clinical suspicion of VAD underwent CDUS of the neck vessels prior to CTA.
      Accuracy, sensitivity and specificity of CDUS and CTA were expressed as
      percentages of agreement with the reference angiographic procedure. Interreader
      concordance for detection of VAD by CTA was calculated with the Cohen K value.
      RESULTS: The CDUS examinations revealed ten out of 15 VAD, with a sensitivity of
      66%, a specificity of 60%, a positive predictive value of 55.5% and a negative
      predictive value of 70.5%. In five cases, CDUS revealed nonspecific wall and flow
      alterations; in eight patients, high resistance obstructive flow; and in two
      patients, intimal flap with demonstration of the true and false lumen. CTA
      enabled the correct identification of all 15 VAD. The reported sensitivity,
      specificity, positive predictive value and negative predictive value were 100%,
      95%, 93.7% and 100%, respectively. With regard to localisation of VAD, CTA showed
      100% correlation with DSA. The differences in CTA and CDUS sensitivity (100% vs
      66%), specificity (95% vs 60%), and overall diagnostic accuracy (97% vs 62.8%),
      assessed by cross tabulations and compared by using the McNemar's two-sided test,
      were significant (p<0.05). CONCLUSIONS: Multidetector CTA is a sensitive
      technique for the diagnosis of VAD. Used as a complement to unenhanced brain CT,
      it has the advantage of being readily available and easy to perform.

PMID- 17440693
TI  - Virtual angioscopy by means of three-dimensional rotational angiography of the
      aortoiliac arteries.
AB  - PURPOSE: The aim of this study was to report the different findings that can be
      visualised with virtual angioscopy starting from rotational angiography (RA) and
      three-dimensional (3D) image processing (3DRA) in the evaluation of the abdominal
      aorta and iliac arteries. MATERIALS AND METHODS: Fifty-seven patients showing an
      occlusive or aneurysmal disease of the abdominal aorta and iliac arteries
      underwent intraarterial digital subtraction angiography (DSA) equipped with the
      RA function and a 3D workstation. We found that 3DRA is able to generate images
      of the examined vessels with a very effective 3D appearance; furthermore, it is
      able to create images of the lumen and wall of the vessel through two different
      modalities: endoviews and cross sections. The possibility of matching high
      density structures (i.e. calcified plaques and stents) to standard 3D
      reconstructions of the examined arteries was applied. RESULTS: Different aspects
      of the arteries can be demonstrated in the angioscopic elaborations: the normal
      and stenotic lumen, artery bifurcations, the collateral vessel origins and the
      severity and extensions of atheromatous calcifications and their relationships to
      the vessel wall. Virtual angioscopy is able to visualise some devices (catheters,
      stents) introduced during diagnostic and interventional procedures. CONCLUSIONS:
      The constant technological evolution of diagnostic imaging is offering new image
      processing techniques, providing new types of previously unexplored information.
      We present a summary of the different radiological findings that can be
      demonstrated with this new imaging technique.

PMID- 17440694
TI  - Endovascular treatment of endoleaks after endovascular abdominal aortic aneurysm
      repair: personal experience.
AB  - PURPOSE: This paper describes the different endovascular treatments (cuffs,
      endografts and embolisation) available for types I, II and III endoleaks
      occurring after endovascular abdominal aortic aneurysm repair (EVAR). MATERIALS
      AND METHODS: From January 2000 to June 2006, 134 patients (118 men, 16 women;
      mean age 75.1 years) underwent EVAR. Ten patients (7%) developed significant
      endoleaks requiring endovascular treatment. RESULTS: Five endoleaks were type I,
      two were type II and three were type III. Of the five type I endoleaks, four were
      proximal and one was distal. The proximal endoleaks were treated by cuff
      deployment, whereas the distal endoleak was treated with a bifurcated graft. Of
      the two patients with type II endoleak, one was treated by translumbar puncture
      and coil embolisation, and the other was treated by superselective embolisation
      of the lumbar feeding vessel with nonresorbable particles. Of the three patients
      with type III endoleak, two were treated by deploying an aortouniiliac endograft
      inside the bifurcated graft and the other by implanting a cuff to restore
      continuity between the graft body and the contralateral limb. Endovascular
      treatment was successful in 6/10 cases, whereas three cases required surgical
      conversion. One patient did not undergo surgery owing to poor general condition.
      CONCLUSIONS: The reported incidence of endoleaks after EVAR is 10%-20%.
      Significant endoleaks should be treated promptly. Endovascular treatment can be
      done with different techniques, but success in not constant due to adverse
      anatomical conditions and technical difficulties.

PMID- 17440695
TI  - Diffusion-weighted MRI in evaluating liver fibrosis: a feasibility study in
      cirrhotic patients.
AB  - PURPOSE: This study was designed to establish whether the measurement of apparent
      diffusion coefficients (ADCs) is clinically accurate in diagnosing liver fibrosis
      in a selected series of cirrhotic patients. MATERIALS AND METHODS: Twenty-eight
      cirrhotic patients (mean age 58.1 years) with histologically proven liver
      fibrosis and 29 healthy controls (mean age 43.8 years) underwent liver diffusion
      weighted magnetic resonance (MR) using a 1.5-Tesla (T) magnet equipped with a
      phased-array coil. Diffusion studies with parallel imaging [generalized
      autocalibrating partially parallel acquisitions (GRAPPA)] were performed within a
      single breath-hold using a single-shot spin-echo echo-planar sequence (TE 74 ms)
      using four b values: b=0, 150, 250 and 400 s/mm(2). A unidirectional diffusion
      gradient was applied. ADCs were measured on ADC maps. RESULTS: Mean ADC was
      significantly lower in cirrhotic livers than in controls (1.11+/-0.16 vs. 1.54+/
      0.12.10(-3)mm(2)/s) (p<0.0001). Receiver operating characteristic (ROC) analysis
      showed an area under the curve (AUC) of 0.96 [confidence interval (CI) 95%:(0.87;
      0.94)], demonstrating higher sensitivity and specificity (92.9% and 100%,
      respectively) for an ADC cutoff of 1.31.10(-3)mm(2)/s. Positive predictive value
      (PPV), negative predictive value (NPV) and overall accuracy were 100%, 99.9% and
      96.4%, respectively. CONCLUSIONS: Diffusion-weighted MRI is an accurate tool in
      evaluating advanced liver fibrosis if an optimised single-shot spin-echo echo
      planar sequence with maximum intermediate b value is used. The ADC threshold for
      liver fibrosis was 1.31.10(-3)mm(2)/s.

PMID- 17440696
TI  - Radiography of the surgical specimen in early stage breast lesions: diagnostic
      reliability in the analysis of the resection margins.
AB  - PURPOSE: The purpose of this study was to evaluate the diagnostic reliability of
      specimen radiography in the assessment of the status of resection margins in
      early stage breast lesions. MATERIALS AND METHODS: The study involved 123
      consecutive patients who underwent breast-conserving surgery for early stage
      breast lesions. Specimen radiography in the two orthogonal views and with direct
      magnification was obtained in all cases to assess presence or absence of the
      lesion, position of the lesion within the surgical specimen and direction in
      which to extend the excision in cases of lesions located close to the margin.
      Diagnostic reliability was evaluated for only 102 patients with malignant
      lesions. RESULTS: Comparison between the radiological and histological diagnoses
      before immediate reexcision had 66% sensitivity, 86% specificity, 74% positive
      predictive value and 81% negative predictive value. Definitive histological
      assessment of margin status, including status after reexcision, was infiltrated
      margins in 23 patients (23%) and clear margins in 79 patients (77%). Definitive
      histological assessment in 12/19 patients (63.15%) with intraoperative
      reexcision, confirmed margin infiltration of the first specimen. Twenty patients
      (20%) underwent a second surgical procedure. CONCLUSIONS: Specimen radiography
      was reliable in identifying clear margins (74% positive predictive value) and
      reduced the rate of reintervention from 31% to 20%. Better results will be
      provided by digital mammographic equipment.

PMID- 17440697
TI  - Adjunctive diagnostic value of ultrasonography evaluation in patients with
      suspected ductal breast disease.
AB  - PURPOSE: The purpose of this study was to evaluate the adjunctive diagnostic
      value of breast ultrasonography (US) in the study of benign ductal breast
      disease. MATERIALS AND METHODS: Fifty-two patients underwent US examinations for
      bloody nipple discharge, palpable retroareolar masses, retroareolar opacities or
      ductal pattern on mammography. US enabled visualisation of mammary-duct ectasia
      (simple or pseudocystic, retroareolar and/or peripheral) and focal masses
      (endoluminal or periductal, with ill-defined or regular margins). All patients
      with nipple discharge underwent cytological evaluation. After the US examination,
      all focal masses with ill-defined margins underwent fine-needle aspiration biopsy
      (FNAB), if necessary. The benign alterations were followed up. RESULTS: In 38/52
      cases, US diagnosed mammary-duct ectasia and in 30/52 cases, the presence of
      focal masses (mean size 7 mm). In the nine women who underwent biopsy,
      histopathological evaluation diagnosed five solitary papillomas, one solitary
      papilloma with a focal area of ductal carcinoma in situ (DCIS), two multiple
      papillomas of the nipple and one papillomatosis. CONCLUSIONS: High-frequency US
      plays an important role in the detection of benign ductal disease both for the
      diagnosis and classification of focal masses and mammary-duct ectasia. US can be
      used as a complementary imaging method to galactography or as a valuable
      alternative when galactography is not available.

PMID- 17440698
TI  - CAD systems for mammography: a real opportunity? A review of the literature.
AB  - The introduction of systems for automated reading in mammography has been
      proposed to improve the sensitivity [computer-aided detection (CADe) systems]
      and, more recently, the specificity [computer-aided diagnosis (CADi) systems] of
      the test. Only CADe systems have been approved by the U.S. Food and Drug
      Administration (FDA) and are used in current practice. These systems are still
      under discussion. Several studies have demonstrated that they are beneficial to
      inexperienced readers and that, through comparison with the computer,
      radiologists are led to improve their performance. However, there is still
      considerable variation among different studies in the level of benefit deriving
      from CAD. Therefore the role of these systems in clinical practice is still
      debated, and their real contribution to the overall management of the diagnostic
      process is not yet clear.

PMID- 17440699
TI  - Pathological animal models in the experimental evaluation of tumour
      microvasculature with magnetic resonance imaging.
AB  - PURPOSE: The purpose of this study was to evaluate the applications of magnetic
      resonance imaging (MRI), and in particular, dynamic contrast-enhanced MRI (DCE
      MRI), in the assessment of tumour microvasculature by means of animal tumour
      models evaluated before and after antiangiogenic treatment. MATERIALS AND
      METHODS: Forty-two MRI exams were performed with intravascular contrast media in
      21 rats: tumours were induced by subcutaneous injection of colon carcinoma cells
      in 7 rats and mammary adenocarcinoma cells in 14 rats. Perfusion and permeability
      parameters of the implanted tumours were evaluated by using two contrast media
      (B22956/1 and Gd-DTPA37-albumin) to establish response to treatment with two
      different antiangiogenic drugs (tamoxifen and SU6668). These parameters were
      correlated with histology to obtain a radiological-histological map of tumour
      microvasculature. RESULTS: DCE-MRI revealed greater enhancement in the peripheral
      area than in the central area in all the examined animal models. In the mammary
      carcinoma experiment, vascular permeability measured by means of B22956/1 in the
      animals treated with the antiangiogenic drug (0.0043317+/-0.0040418 ml/min(
      1)/ml(-1)) was significantly less than in untreated animals (0.0090460+/
      0.0043680 ml/min(-1)/ml(-1)), whereas no significant difference was observed with
      Gd-DTPA-albumin (13.14+/-13.94 ml/min(-1)/ml(-1) in treated animals and 18.07+/
      11.92 ml/min(-1)/ml(-1) in untreated animals). In the colon carcinoma experiment,
      mean permeability and perfusion decreased by 51% (from 5.2+/-1.1 to 2.5+/-0.8
      ml/100 ml) and 59% (from 0.00165+/-5.1 to 0.0067+/-4.8 ml/min(-1)/ml(-1) of
      tissue), respectively, in all animals after antiangiogenic drug administration.
      CONCLUSIONS: DCE-MRI permits a noninvasive evaluation of tumour microcirculation
      and in particular of its dynamic characteristics and vascularity before and after
      antiangiogenic treatment.

PMID- 17440700
TI  - The radiologist's role in managing paediatric liver transplantation: personal
      experience with 40 patients.
AB  - PURPOSE: The aim of our study was to evaluate the radiologist's role in managing
      paediatric orthotopic liver transplantation (OLT) through a retrospective review
      of our experience in diagnosing and treating post-OLT complications. MATERIALS
      AND METHODS: Forty children (mean age 4.6 years) underwent 44 OLTs over 71
      months. The follow-up period (mean 724 days) was divided into three phases:
      hospital stay, up to three months after discharge and subsequent period. The
      number and type of radiological examinations, radiologically detectable
      complications and interventional procedures were analysed. RESULTS: Most
      examinations were carried out with ultrasound (US) (859/931 of all radiological
      studies performed during the first two phases, 92.3%). Colour-Doppler US enabled
      early detection and treatment of all vascular complications (9/40, 22.5% of
      patients; 13 complications in nine patients, eight arterial and five portal
      complications; 1.4 for each patient with complications). Computed tomography (CT)
      or angiography was very rarely employed. US also detected biliary complications
      (11 patients, 27.5%: three cases of segmental ducts excluded from the
      anastomosis, four cases of stenosis of the biliodigestive anastomosis, one
      lithiasis, three stenoses associated with lithiasis), which were successfully
      managed in 75% of the cases treated with interventional radiology procedures
      (percutaneous bilioplasty and/or lithotripsy). At the time of writing this paper,
      the patient survival rate was 100%, and the organ survival rate was 91% (40/44).
      There were four re-transplantations: three due to hepatic artery thrombosis and
      one to biliary stenosis with lithiasis. CONCLUSIONS: The radiologist's role is
      fundamental for early sonographic diagnosis of post-OLT complications in
      children. Vascular complications are often associated in a single patient, and
      early treatment may improve the prognosis. Interventional radiology represents a
      safe and effective treatment for many biliary complications.

PMID- 17440701
TI  - [Vascular interventions and reconstructive plastic surgery. Optimizing the
      treatment of chronic wounds].
AB  - Despite the high prevalence of arterial occlusive disease, only a few studies
      have investigated the benefit of interventions to recanalize extremity arteries
      prior to plastic operations to close chronic wounds. The purpose of this study
      was to investigate the correlation of simple clinical examinations and apparative
      diagnostics of arterial occlusive disease of the lower extremity in patients with
      chronic wounds and to evaluate the benefit of vascular procedures to optimize
      wound perfusion before surgical closure. A total of 150 individuals with chronic
      wounds were included in this retrospective study. All patients underwent
      palpation of their foot pulses, Doppler sonography, and measurement of occlusive
      pressure. Positive results were tested by angiography. All patients with
      peripheral extremity vessel occlusion underwent vascular interventions prior to
      plastic operations for definitive wound closure. In all 34 patients with missing
      foot pulses, the clinical diagnosis of arterial occlusion could be confirmed by
      angiography. Peripheral recanalization and improved wound perfusion could be
      achieved in all patients. Arterial insufficiency could be diagnosed rapidly and
      safely using simple clinical examination such as palpation of foot pulses or
      measurement of occlusive pressures combined with Doppler sonography. Thus this
      simple and straightforward algorithm helped to secure the success of surgical
      therapy by shortening the time until wound-healing and reducing the psychosocial
      burden on the patient and financial costs to the health care system.

PMID- 17440702
TI  - [Basal cell carcinoma. Molecular genetics and unusual clinical features].
AB  - Basal cell carcinoma is the most common human cancer. Its incidence is steadily
      increasing. The development of basal cell carcinoma is linked to genetic factors,
      including the individual skin phototype, as well as the cumulative exposure to
      UVB. The vast majority of basal cell carcinomas are sporadic tumors, while
      familial cases associated with certain hereditary syndromes are less common. At
      the molecular level, basal cell carcinomas are characterized by aberrant
      activation of sonic hedgehog signaling, usually due to mutations either in the
      ptch or smoh genes. In addition, about half of the cases carry mutations in the
      tp53 tumor suppressor gene, which are often UVB-associated C-->T transition
      mutations. Clinically, basal cell carcinomas may show a high degree of
      phenotypical variability. In particular, tumors occurring in atypical locations,
      showing an unusual clinical appearance, or imitating other skin diseases may
      cause diagnostic problems. This review article summarizes the current state of
      the art concerning the etiology, predisposition and molecular genetics of basal
      cell carcinoma. In addition, examples of unusual clinical manifestations are
      illustrated.

PMID- 17440704
TI  - Flower-visiting behavior of male bees is triggered by nectar-feeding insects.
AB  - Bees are important pollinators for many flowering plants. Female bees are thought
      to be more effective pollinators than male bees because they carry much more
      pollen than males. Males of some solitary bee species are known to patrol near
      flowers that females visit. Because patrolling males visit flowers to mate or
      defend their territories, they may function as pollinators. However, the
      significance of patrolling males to pollination has not been studied. We studied
      males of a solitary bee, Heriades fulvohispidus (Megachilidae), patrolling near
      flowers and visiting flowers that attracted nectar-feeding insects, including
      conspecifics, on the Ogasawara (Bonin) Islands. To test the hypothesis that
      patrolling male bees may function as pollen vectors, we compared the frequency of
      visits by H. fulvohispidus to flowers of an endemic plant, Schima mertensiana
      (Theaceae); comparisons were made among flowers with a dead H. fulvohispidus, a
      dead beetle, a piece of plastic, and nothing (control flowers). Patrolling H.
      fulvohispidus more frequently visited flowers with a dead conspecific, a dead
      beetle, or a piece of plastic than the control flowers. Our experiment
      demonstrates that nectar-feeding insects (including conspecifics and other
      insects) enhance the flower-visiting frequency of patrolling H. fulvohispidus
      males on S. mertensiana flowers. Furthermore, we observed S. mertensiana pollen
      on patrolling males as well as females, suggesting that male bees may also
      function as pollen vectors.

PMID- 17440703
TI  - A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death
      underlies familial chilblain lupus.
AB  - We recently described a novel autosomal-dominant genodermatosis, termed familial
      chilblain lupus, and mapped its genetic locus to chromosome 3p21. Familial
      chilblain lupus manifests in early childhood with ulcerating acral skin lesions
      and is associated with arthralgias and circulating antinuclear antibodies. In
      this study, we report the identification of a heterozygous missense mutation
      (D18N) in TREX1 encoding the 3'-5'repair exonuclease 1 in affected individuals of
      the family with chilblain lupus. The homodimeric TREX1 is the most abundant
      intracellular DNase in mammalian cells. We have recently shown that TREX1 plays a
      role in apoptotic single-stranded DNA damage induced by the killer lymphocyte
      protease granzyme A. D18N affects a highly conserved amino acid residue critical
      for catalytic activity. Recombinant mutant TREX1 homodimers are enzymatically
      inactive, while wild type/mutant heterodimers show residual exonucleolytic
      activity, suggesting a heterozygous loss of function. Lymphoblastoid cells
      carrying the D18N mutation are significantly less sensitive to granzyme A
      mediated cell death, suggesting a novel role for this caspase-independent form of
      apoptosis in the pathogenesis of familial chilblain lupus. Our findings also
      warrant further investigation of TREX1 in common forms of lupus erythematosus.

PMID- 17440705
TI  - Gene expression heterogeneity in human islet endocrine cells in vitro: the
      insulin signalling cascade.
AB  - AIMS/HYPOTHESIS: Insulin secretion is a highly regulated mechanism involving a
      complex insulin-dependent network of communication between alpha, beta and delta
      cells. However, whereas the role of insulin in beta cells has been well
      documented, very little is known about its role in alpha and delta cells. Having
      recently demonstrated heterogeneity of insulin receptor (INSR) isoform expression
      in these three endocrine cell types, our current study aimed to characterise the
      expression pattern of the multiple isoforms involved in the insulin signal
      transduction cascade in human alpha, beta and delta cells in vitro. MATERIALS AND
      METHODS: cDNA samples prepared from single human islet cells were subjected to
      nested PCRs. RESULTS: Of 706 cells analysed, 15% were alpha cells, 28% beta
      cells, 8% delta cells and 46% non-endocrine cells. Profiling of expression of the
      insulin signalling cascade elements showed a heterogeneity between islet cell
      types, although at least one member of each protein family was expressed in the
      three populations of endocrine cells. Thus, the mRNAs coding for INSR-B,
      phosphoinositide-dependent protein kinase-1 and the human homologue of v-akt
      murine thymoma viral oncogene homologue 1 (AKT1) could not be detected in alpha
      cells, but were expressed by beta and delta cells. In addition, while the insulin
      receptor substrates IRS1 and IRS2, phosphoinositide-3-kinase, catalytic, beta
      polypeptide (PIK3CB) and AKT2 were expressed with relatively low frequencies in
      alpha and delta cells (<17% for IRS1, IRS2, PIK3CB; <25% for AKT2), their
      frequencies of expression in beta cells were 50, 33, 33 and 100%, respectively.
      CONCLUSIONS/INTERPRETATION: Our results suggest that insulin signalling cascade
      elements in human alpha, beta and delta cells have distinct expression patterns.

PMID- 17440706
TI  - [Femoral head necrosis. Current status and potential future therapy concepts].

PMID- 17440707
TI  - [Correction of rheumatic forefoot. The value of a combined arthrodesis of the
      first toe and resection of metatarsal heads 2-5].
AB  - INTRODUCTION: Resection of the metatarsal heads is an established procedure for
      the therapy of rheumatic forefoot deformations. However, a recurrence of lateral
      deviation of the lesser toes and painful plantar keratosis remain a challenging
      problem for the treatment of these patients. The aim of this study was to
      evaluate our results in cases of rheumatoid forefoot deformities. We performed a
      resection of the metatarsal heads 2-5 in combination with an arthrodesis of the
      first toe and resection of keratosis by the plantar approach. MATERIAL AND
      METHODS: Fifteen patients (20 feet) were followed-up clinically and
      radiologically using the American Orthopedic Foot and Ankle Society (AOFAS),
      Miehlke-, and Larsen scores. RESULTS: Average follow-up time was 3.5 years
      (range: 1.5-7.5 years). An average AOFAS score of 81/90 was found for the hallux
      and 90/100 for the lesser toes. A total of 18 feet were rated as pain free, while
      two feet showed some residual pain. Every case showed an harmonic cascade of the
      resection. All patients stated that the operation had improved their quality of
      life and that they would consent to undergoing it again. CONCLUSION: Our results
      after arthrodesis of MP-1 and resection of the metatarsal heads 2-5 using the
      plantar approach were good compared to the data published in the literature.

PMID- 17440708
TI  - Arthroscopic footprint reconstruction of a bone cyst-associated rotator cuff
      tear.
AB  - Arthroscopic treatment of a symptomatic rotator cuff tear is problematic when the
      tear is associated with a large bone cyst. We describe procedure of arthroscopic
      bone grafting in the bone cyst and footprint reconstruction of the rotator cuff
      tear using a suture-bridge technique.

PMID- 17440709
TI  - Synthetic esters recognized by glucuronoyl esterase from Schizophyllum commune.
AB  - Glucuronoyl esterase is a novel carbohydrate esterase recently discovered in the
      cellulolytic system of the wood-rotting fungus Schizophyllum commune on the basis
      of its ability to hydrolyze methyl ester of 4-O-methyl-D-glucuronic acid. This
      substrate was not fully corresponding to the anticipated function of the enzyme
      to hydrolyze esters between xylan-bound 4-O-methyl-D-glucuronic acid and lignin
      alcohols occurring in plant cell walls. In this work we showed that the enzyme
      was capable of hydrolyzing two synthetic compounds that mimic the ester linkages
      described in lignin-carbohydrate complexes, esters of 4-O-methyl-D-glucuronic and
      D-glucuronic acid with 3-(4-methoxyphenyl)propyl alcohol. A comparison of
      kinetics of hydrolysis of methyl and 3-(4-methoxyphenyl)propyl esters indicated
      that the glucuronoyl esterase recognizes the uronic acid part of the substrates
      better than the alcohol type. The catalytic efficiency of the enzyme was much
      higher with the ester of 4-O-methyl-D-glucuronic acid than with that of D
      glucuronic acid. Examination of the action of glucuronoyl esterase on a series of
      methyl esters of 4-O-methyl-D-glucopyranuronosyl residues alpha-1,2-linked to
      xylose and several xylooligosaccharides suggested that the rate of
      deesterification is independent of the character of the carbohydrate part
      glycosylated by the 4-O-methyl-D-glucuronic acid.

PMID- 17440710
TI  - Characterization of a novel T4-type Stenotrophomonas maltophilia virulent phage
      Smp14.
AB  - Stenotrophomonas maltophilia (Sm), with most of the isolates being resistant to
      multidrugs, is an opportunistic bacterium causing nosocomial infections. In this
      study, a novel virulent Sm phage, Smp14, was characterized. Electron microscopy
      showed that Smp14 resembled members of Myoviridae and adsorbed to poles of the
      host cells during infection. It lysed 37 of 87 clinical Sm isolates in spot test,
      displayed a latent period of ca. 20 min, and had a burst size of ca. 150. Its
      genome (estimated to be 160 kb by PFGE), containing m4C and two unknown modified
      bases other than m5C and m6A as identified by HPLC, resisted to digestion with
      many restriction endonucleases except MseI. These properties indicate that it is
      a novel Sm phage distinct from the previously reported phiSMA5 which has a genome
      of 250 kb digestible with various restriction enzymes. Sequencing of a 16 kb
      region revealed 12 ORFs encoding structural proteins sharing 15-45% identities
      with the homologues from T4-type phages. SDS-PAGE displayed 20 virion proteins,
      with the most abundant one being the 39 kDa major capsid protein (gp23), which
      had the N-terminal 52 amino acids removed. Phylogenetic analysis based on gp23
      classified Smp14 into a novel single-membered T4-type subgroup.

PMID- 17440712
TI  - Use of single-drop microextraction for determination of fentanyl in water
      samples.
AB  - Fentanyl is a very potent synthetic narcotic analgesic. Because of its strong
      sedative properties, it has become an analogue of illicit drugs such as heroin.
      Its unambiguous detection and identification in environmental samples can be
      regarded as strong evidence of its illicit preparation. In this paper we report
      application of single-drop microextraction (SDME) for analysis of water samples
      spiked with fentanyl. Experimental conditions which affect the performance of
      SDME, for example the nature of the extracting solvent, sample stirring speed,
      extraction time, ionic strength, and solution pH, were optimized. The method was
      found to be linear in the concentration range 0.10-10 ng mL(-1). The limits of
      quantitation and detection of the method were 100 pg mL(-1) and <75 pg mL(-1),
      respectively. This technique is superior to other sample-preparation techniques
      because of the simple experimental set-up, short analysis time, high sensitivity,
      and minimum use of organic solvent.

PMID- 17440711
TI  - Anti-aggressive effects of agonists at 5-HT1B receptors in the dorsal raphe
      nucleus of mice.
AB  - RATIONALE: In rodents, serotonin 1B (5-HT(1B)) agonists specifically reduce
      aggressive behaviors, including several forms of escalated aggression. One form
      of escalated aggression is seen in mice that seek the opportunity to attack
      another mouse by accelerating their responding during a fixed interval (FI)
      schedule. Responses preceding the opportunity to attack may reflect aggressive
      motivation. OBJECTIVE: This study investigated the effects of two 5-HT(1B)
      receptor agonists on the motivation to fight and the performance of heightened
      aggression. MATERIALS AND METHODS: Male mice were housed as "residents" and
      performed nose-poke responses on an FI 10-min schedule with the opportunity to
      briefly attack an "intruder" serving as the reinforcer. In the first experiment,
      the 5-HT(1B) receptor agonist, CP-94,253 (0-10 mg/kg, IP), was given 30 min
      before the FI 10 schedule. To confirm that CP-94,253 achieved its effects via 5
      HT(1B) receptors, the 5HT(1B/1D) receptor antagonist, GR 127,935 (10 mg/kg, IP)
      was administrated before the agonist injection. In the second experiment, the 5
      HT(1B) agonist CP-93,129 (0-1.0 microg) was microinjected into the dorsal raphe
      10 min before the FI 10 schedule. RESULTS: The agonists had similar effects on
      all behaviors. CP-94,253 and CP-93,129 significantly reduced the escalated
      aggression towards the intruder at doses lower than those required to affect
      operant responding. The highest doses of CP-94,253 (10 mg/kg) and CP-93,129 (1.0
      microg) decreased the rate and accelerating pattern of responding during the FI
      10 schedule; lower doses were less effective. GR 127,935 antagonized CP-94,253's
      effects on all other behaviors, except response rate. CONCLUSIONS: These data
      extend the anti-aggressive effects of 5-HT(1B) agonists to a type of escalated
      aggression that is rewarding and further suggest that these effects are
      associated with actions at 5-HT(1B) receptors in the dorsal raphe.

PMID- 17440713
TI  - Preparation and characterization of standard reference material 3276, carrot
      extract in oil.
AB  - The National Institute of Standards and Technology (NIST), the Food and Drug
      Administration (FDA) Center for Drug Evaluation and Research (CDER) and Center
      for Food Safety and Applied Nutrition (CFSAN), and the National Institutes of
      Health (NIH), Office of Dietary Supplements (ODS) are collaborating to produce a
      series of standard reference materials (SRMs) for dietary supplements. Standard
      reference material (SRM) 3276 Carrot Extract in Oil is one in this series, with
      values assigned for trans-alpha-carotene, trans- and total beta-carotene, delta-
      and gamma-tocopherol, and twelve fatty acids. Results for carotenoids and
      tocopherols were obtained by use of combinations of liquid chromatography (LC),
      on columns of differing selectivity, with absorbance and mass spectrometric (MS)
      detection. Fluorescence detection also was used for the tocopherols. Results for
      fatty acids were obtained by use of gas chromatography (GC) with both flame
      ionization and mass-spectrometric detection. This material is intended for use as
      a primary control material when assigning values to in-house (secondary) control
      materials and for validation of analytical methods for measurement of these
      analytes in similar matrices.

PMID- 17440714
TI  - Noninvasive monitoring of intracellular pH change induced by drug stimulation
      using silica nanoparticle sensors.
AB  - We have synthesized and applied a nanoparticle-based pH sensor for noninvasive
      monitoring of intracellular pH changes induced by drug stimulation. The pH sensor
      is a two-fluorophore-doped nanoparticle sensor (2DFNS) that contains a pH
      sensitive indicator (fluorescein isothiocyanate, FITC) and a reference dye
      (tris(2,2'-bipyridyl)dichlororuthenium(II) hexahydrate, RuBPY). The nanoparticles
      have an average diameter of 42 +/- 3 nm and can easily be taken up by cells for
      noninvasive intracellular pH measurement. The 2DFNS exhibited excellent pH
      sensitivity, reversibility, and a dynamic range of pH 4-7 for biological studies.
      We have used 2DFNS to monitor pH changes in living cells by drug stimulation.
      Both lysosomal pH changes in murine macrophages stimulated by chloroquine and
      intracellular acidification in apoptotic cancer cells were monitored in real time
      and with high pH sensitivity. Hela cells underwent intracellular acidification
      with a drop in pH from 7.2 to 6.5 after 8 h of treatment with 2 mumol/L
      dexamethasone, and this intracellular pH drop in the apoptotic cells was not
      influenced by the addition of zinc ions. The application of 2DFNS to
      intracellular pH measurements yields some important advantages: excellent pH
      sensitivity, little environmental effect on the pH dye, excellent quantification,
      high stability and excellent reversibility.

PMID- 17440715
TI  - The impact of new technology in the treatment of cystine stones.
AB  - Cystinuric patients frequently require stone removing procedures because of their
      high tendency to have recurrent urinary calculi. In the last 20 years the
      morbidity of stone treatment has been reduced by the introduction of endourologic
      procedures and shock wave lithotripsy (SWL), but cystine stones are not amenable
      to all minimally invasive procedures. The aim of our study was to assess the
      impact of new technology in the treatment of cystine stones. The records of
      patients observed at our institutions from 1978 to 2005 were reviewed. We
      retrospectively analysed the previous stone histories of all the patients who
      presented at our institutions for stone treatment who resulted to be cystinuric
      at our metabolic work up. Patients were divided in two groups according to the
      date of our first observation: group A comprised patients observed from 1978 to
      1989 who mainly experienced traditional stone treatment and group B patients
      observed from 1990 to present who were preferentially treated with minimally
      invasive therapeutic modalities. A total of 48 cystinuric patients were observed
      (31 in group A and 17 in group B). The mean age (38 +/- 15 vs. 36 +/- 13 years),
      the age at stone onset (21 +/- 11 vs. 21 +/- 12) and the annual recurrence rate
      (1.34 +/- 2.38 vs. 1.16 +/- 1.11 stones/year/pt) were not significantly different
      in the two groups. The male/female ratio was 18/13 and 8/9, respectively, in
      group A and B. In group A 16 patients underwent open surgical treatment for a
      total of 29 procedures (0.93 for patient) and four of them had nephrectomy; in
      group B only eight underwent open surgery but other seven had percutaneous
      surgery (0.47 + 0.41 procedure/patient). In group B 37 SWL treatments were
      performed (2.17 for patient) whereas patients in group A underwent only four
      SWLs. Renal function was impaired in six patients (19%) in group A with a patient
      requiring haemodyalitic treatment and in one patient (6%) in group B. Compared to
      the traditional stone treatment, after 1990 fewer cystinuric patients required
      open surgery and none underwent nephrectomy or developed severe renal failure.
      Our results indicate that the actual care of patients with cystine stones should
      still be improved requiring a comprehensive approach in order to avoid
      inappropriate SWL treatments and more attention to early diagnosis and preventive
      measures.

PMID- 17440716
TI  - Characterization of sequential exocytosis in a human neuroendocrine cell line
      using evanescent wave microscopy and "virtual trajectory" analysis.
AB  - Secretion of hormones and other bioactive substances is a fundamental process for
      virtually all multicellular organisms. Using total internal reflection
      fluorescence microscopy (TIRFM), we have studied the calcium-triggered exocytosis
      of single, fluorescently labeled large, dense core vesicles in the human
      neuroendocrine BON cell line. Three types of exocytotic events were observed: (1)
      simple fusions (disappearance of a fluorescent spot by rapid diffusion of the dye
      released to the extracellular space), (2) "orphan" fusions for which only rapid
      dye diffusion, but not the parent vesicle, could be detected, and (3) events with
      incomplete or multi-step disappearance of a fluorescent spot. Although all three
      types were reported previously, only the first case is clearly understood. Here,
      thanks to a combination of two-color imaging, variable angle TIRFM, and novel
      statistical analyses, we show that the latter two types of events are generated
      by the same basic mechanism, namely shape retention of fused vesicle ghosts which
      become targets for sequential fusions with deeper lying vesicles. Overall,
      approximately 25% of all exocytotic events occur via sequential fusion. Secondary
      vesicles, located 200-300 nm away from the cell membrane are as fusion ready as
      primary vesicles located very near the cell membrane. These findings call for a
      fundamental shift in current models of regulated secretion in endocrine cells.
      Previously, sequential fusion had been studied mainly using two-photon imaging.
      To the best of our knowledge, this work constitutes the first quantitative report
      on sequential fusion using TIRFM, despite its long running and widespread use in
      studies of secretory mechanisms.

PMID- 17440717
TI  - Annexin A4 binding to anionic phospholipid vesicles modulated by pH and calcium.
AB  - Annexin A4 belongs to a class of Ca(2+)-binding proteins for which different
      functions in the cell have proposed, e.g. involvement in exocytosis and in the
      coagulation process. All these functions are related to the ability of the
      annexins to bind to acidic phospholipids. In this study the interaction of
      annexin A4 with large unilamellar vesicles (LUV) prepared from phosphatidylserine
      (PS) or from phosphatidic acid (PA) is investigated at neutral and acidic pH.
      Annexin A4 strongly binds to either lipid at acidic pH, whereas at neutral pH
      only weak binding to PA and no binding to PS occurs. Addition of 40 microM Ca(2+)
      leads to a strong binding to the lipids also at neutral pH. This is caused by the
      different electric charge of the protein below and above its isoelectric point.
      Binding of annexin A4 induces dehydration of the vesicle surface. The strength of
      the effects is much greater at pH 4 than at pH 7.4. At pH 7.4 annexin A4 reduces
      the Ca(2+)-threshold concentration necessary to induce fusion of PA LUV. The
      Ca(2+) induced fusion of PS LUV is not affected by annexin A4 at pH 7.4. At pH 4
      annexin A4 induces fusion of either vesicles without Ca(2+). Despite the low
      binding extents at neutral pH annexin A4 induces a Ca(2+) independent leakage of
      PS- or PA-LUV. The leakage extent is increased at acidic pH. From the data two
      suggestions are made: (1) At pH 4 annexin A4 (at least partially) penetrates into
      the bilayer in contrast to the preferred location at the vesicle surface at
      neutral pH. The conformation of annexin A4 seems to be different at the two
      conditions. (2) At neutral pH, Annexin A4 seems to be able to bind two PA
      vesicles simultaneously; however, only one PS vesicle at the same time. This
      behavior might be related to a recently described double Ca(2+) binding site,
      which appears to be uniquely suited for PS.

PMID- 17440718
TI  - Contribution of single nucleotide polymorphisms of the IL1A gene to the cleavage
      of precursor IL-1alpha and its transcription activity.
AB  - We previously demonstrated the association of IL1A gene single nucleotide
      polymorphisms (SNPs) with susceptibility to systemic sclerosis (SSc) patients. In
      this study, we explored the effects of SNP on the transcriptional activity and
      processing of the precursor IL-1alpha (pre-IL-1alpha) in skin fibroblasts. Two
      kinds of promoter regions of the IL1A gene were prepared including C or T at 
      889, referred to C/IL1A and T/IL1A, and inserted into a luciferase reporter
      vector (pGL3). Skin fibroblasts were explanted from two SSc patients whose
      genomic DNA contained GG and TT genotypes at +4845 of the IL1A gene,
      respectively. Cell lysates were collected and reacted with various concentrations
      of calpain, and then the processing of pre-IL-1alpha was analyzed by Western
      blotting using monoclonal anti-IL-1alpha antibody. A SNP was determined by the
      allelic discrimination method using fluorescence-labeled Taq-Man probes.
      Significant differences in the luciferase activities were not detected between
      pGL3 (C/IL1A) and pGL3 (T/IL1A) in SSc fibroblasts. Calpain required a 100-fold
      higher concentration to process the pre-IL-1alpha containing Ala at the 114th
      amino acid than that to do containing Ser. The frequency of the GG genotype was
      significantly higher in SSc patients than that in healthy donors, whereas the
      frequency of TT genotype was significantly higher in RA patients than that in
      healthy donors. Our observation showed that the SNP at +4845 affected the
      enzymatic efficiency of the protease in cleaving pre-IL-1alpha. Pre-IL-1alpha
      with Ala, which was high in frequency in SSc patients, was more resistant to be
      cleaved by proteases in human sera than pro-IL-1alpha with Ser.

PMID- 17440719
TI  - Co-existence of physiologically similar sulfate-reducing bacteria in a full-scale
      sulfidogenic bioreactor fed with a single organic electron donor.
AB  - A combination of culture-dependent and independent methods was used to study the
      co-existence of different sulfate-reducing bacteria (SRB) in an upflow anaerobic
      sludge bed reactor treating sulfate-rich wastewater. The wastewater was fed with
      ethanol as an external electron donor. Twenty six strains of SRB were randomly
      picked and isolated from the highest serial dilution that showed growth (i.e.
      10(8)). Repetitive enterobacterial palindromic polymerase chain reaction and
      whole cell protein profiling revealed a low genetic diversity, with only two
      genotypes among the 26 strains obtained in the pure culture. The low genetic
      diversity suggests the absence of micro-niches within the reactor, which might be
      due to a low spatial and temporal micro-heterogeneity. The total 16S rDNA
      sequencing of two representative strains L3 and L7 indicated a close relatedness
      to the genus Desulfovibrio. The two strains differed in as many as five
      physiological traits, which might allow them to occupy distinct niches and thus
      co-exist within the same habitat. Whole cell hybridisation with fluorescently
      labeled oligonucleotide probes was performed to characterise the SRB community in
      the reactor. The isolated strains Desulfovibrio L3 and Desulfovibrio L7 were the
      most dominant SRB, representing 30-35% and 25-35%, respectively, of the total SRB
      community. Desulfobulbus-like bacteria contributed for 20-25%, and the
      Desulfobacca acetoxidans-specific probe targeted approximately 15-20% of the
      total SRB. The whole cell hybridisation results thus revealed a consortium of
      four different species of SRB that can be enriched and maintained on a single
      energy source in a full-scale sulfidogenic reactor.

PMID- 17440720
TI  - Quantitative analysis of a high-rate hydrogen-producing microbial community in
      anaerobic agitated granular sludge bed bioreactors using glucose as substrate.
AB  - Fermentative H(2) production microbial structure in an agitated granular sludge
      bed bioreactor was analyzed using fluorescence in situ hybridization (FISH) and
      polymerase chain reaction-denatured gradient gel electrophoresis (PCR-DGGE). This
      hydrogen-producing system was operated at four different hydraulic retention
      times (HRTs) of 4, 2, 1, and 0.5 h and with an influent glucose concentration of
      20 g chemical oxygen demand/l. According to the PCR-DGGE analysis, bacterial
      community structures were mainly composed of Clostridium sp. (possibly
      Clostridium pasteurianum), Klebsiella oxytoca, and Streptococcus sp. Significant
      increase of Clostridium/total cell ratio (68%) was observed when the reactor was
      operated under higher influent flow rate. The existence of Streptococcus sp. in
      the reactor became more important when operated under a short HRT as indicated by
      the ratio of Streptococcus probe-positive cells to Clostridium probe-positive
      cells changing from 21% (HRT 4 h) to 38% (HRT 0.5 h). FISH images suggested that
      Streptococcus cells probably acted as seeds for self-flocculated granule
      formation. Furthermore, combining the inspections with hydrogen production under
      different HRTs and their corresponding FISH analysis indicated that K. oxytoca
      did not directly contribute to H(2) production but possibly played a role in
      consuming O(2) to create an anaerobic environment for the hydrogen-producing
      Clostridium.

PMID- 17440721
TI  - Carbon monoxide signalling reduces photocarcinogenesis in the hairless mouse.
AB  - Exposure of the skin of mice to UVA (320-400 nm) radiation has been shown to
      provide protection against the immunosuppressive effects of UVB (290-320 nm)
      radiation. The UVA protection was mediated via the UVA induction of the stress
      protein heme oxygenase-1, and its enzymatic product carbon monoxide (CO). Because
      UVB-induced immunosuppression is an accompanying and prerequisite feature of the
      promotion phase of photocarcinogenesis, the potential for immunoprotective CO to
      act as an anti-skin cancer agent was tested in this study. Groups of female
      albino Skh:hr-1 hairless mice were irradiated chronically with daily minimally
      erythemogenic doses of solar simulated UV radiation (SSUV) during a 10 week
      period to induce photocarcinogenesis. The effect of repeated topical application
      of lotions containing a CO-releasing molecule (CORM-2;
      tricarbonyldichlororuthenium (II) dimer) at 250 or 500 microM, that had
      previously been shown in short-term experiments to provide photoimmune protection
      in mice, was measured. Tumor development was monitored for 29 weeks. Topical CORM
      2 treatment was observed to reduce the acute and chronic inflammatory erythema
      reaction compared with control irradiated mice that did not receive CORM-2
      lotions, and to reduce the chronic epidermal hyperplasia accompanying tumor
      outgrowth. The CORM-2 treatments provided a significant moderate inhibition of
      early tumor appearance dose-dependently, significantly reduced the average tumor
      multiplicity, increased the regression of established tumors dose-dependently,
      and inhibited the formation of large locally invasive tumors. The CORM-2
      treatments also reduced the expression of immunosuppressive IL-10 in the
      uninvolved epidermis and dermis of tumor-bearing mice, and enhanced
      immunopotentiating epidermal IL-12 expression. Therefore CO signalling was
      revealed to have previously unrecognized anti-carcinogenic functions in the skin,
      consistent with a protective modulation of the epidermal cytokines. This is a
      novel observation that also implies that the UVA waveband that produces CO
      physiologically in exposed skin, might likewise be found to have an anti
      photocarcinogenic action.

PMID- 17440722
TI  - Pattern of serum immunoreactivity against breast cancer cell lysates may predict
      severity of disease in breast cancer patients.
AB  - Humoral tumor-specific immunity has been investigated as a potential tool to
      identify tumor-associated antigens and evaluate cancer diagnosis and prognosis.
      Using SDS-PAGE and western blotting techniques we investigated the humoral immune
      response against tumor cell antigens in 36 breast cancer patients, 17 node
      positive (NP) and 19 node-negative (NN). As a source of antigens, we prepared
      protein lysates from four breast cancer cell lines (AU565, BT474, MCF-7 and MDA
      MB-231) which in vitro exhibit different features of invasion, estrogen
      receptor/progesterone receptor status and HER2/neu expression thereby potentially
      representing mild to aggressive forms of clinical disease. A higher number of
      immunocomplexes Ag-Ab were formed when serum from NN patients was immunoreacted
      against lysates from AU565 and MCF-7 in comparison to serum from NP patients (P <
      0.01). BT474 cells were not a good antigenic source. MDA-MB-231 cells could not
      significantly discriminate between NN and NP patients since both groups showed
      higher amounts of reactivity against the lysate. However, comparative analysis of
      protein preparations purified from MCF-7 and MDA-MB-231 cells and immunodetected
      concomitantly with the same serum samples showed that serum from patients with
      cancers with worse prognosis (stage, nodality, HER2/neu and hormonal status)
      reacted more intensely to proteins purified from the relatively more invasive
      cell line MDA-MB-231 compared to MCF-7. These findings suggest that the study of
      serum antibody reactivity to antigens purified from breast cancer cell lines with
      different invasive properties should be further investigated for its potential in
      providing beneficial prognostic information in breast cancer.

PMID- 17440723
TI  - Single administration of low dose cyclophosphamide augments the antitumor effect
      of dendritic cell vaccine.
AB  - Single administration of low dose cyclophosphamide (CTX) was previously reported
      to enhance the antitumor efficacy of immunotherapies. To investigate the possible
      mechanisms for this effect, we examined whether a single administration of low
      dose CTX could augment the immunogenicity of dendritic cell (DC) vaccines. Fifty
      milligrams per kilogram body weight dose of CTX was administrated
      intraperitoneally to mice after B16 melanoma or C26 colon carcinoma tumor models
      were established, DC vaccine generated from mouse bone marrow and pulsed with B16
      or C26 tumor cells lysates were vaccinated 4 days later. CTX treatment
      potentiated the antitumor effects of the DC vaccine, and increased the proportion
      of IFN-gamma secreting lymphocytes in spleens. Furthermore, a significantly
      reduced proportion of CD4+CD25+FoxP3+ regulatory T (Treg) cells was detected by
      flow cytometry in spleen lymphocytes from tumor-bearing mice treated with CTX.
      Thus, a single administration of low dose CTX could augment antitumor immune
      responses of DC vaccine by reducing the proportion of CD4+CD25+FoxP3+ Treg cells
      in tumor-bearing mice. Our results suggested a possible mechanism of CTX-induced
      immunopotentiation and provided a strategy of immunotherapy combining a low dose
      CTX with DC vaccine.

PMID- 17440724
TI  - In situ detection of antigen-specific T cells in cryo-sections using MHC class I
      tetramers after dendritic cell vaccination of melanoma patients.
AB  - Application of tetrameric MHC class I-peptide complexes has significantly
      improved the monitoring of antigen-specific T cell immune responses in mouse
      models as well as in clinical studies. Especially MHC class I tetramer analysis
      of tumor-specific T cells in suspension or on thick vibratome sections from
      viable tissue has been proven extremely useful. Using the well-characterized
      mouse tyrosinase-related-protein-2 specific cytotoxic T cell (CTL) clone LP9, we
      now developed a method that allows for specific identification of T cells with
      MHC class I tetramers in 8 mum thick, chemically fixed cryosections. The protocol
      was validated in a murine influenza virus-infection model. Moreover, analysis of
      delayed type hypersensitivity (DTH) skin biopsies from melanoma patients
      vaccinated with peptide-loaded mature dendritic cells, revealed the presence and
      location of anti-tumor CTLs. The specificity of the CTLs detected in situ
      correlated with both the DTH challenge specificity and reactivity of cell
      suspensions derived from the same biopsies. Collectively, our data demonstrate
      that in situ MHC class I tetramer staining provides a valuable tool to reveal the
      presence and anatomical location of specific CTLs in frozen tissue following
      immune-based treatment strategies in cancer patients.

PMID- 17440725
TI  - A phase II open-label study of DHA-paclitaxel (Taxoprexin) by 2-h intravenous
      infusion in previously untreated patients with locally advanced or metastatic
      gastric or oesophageal adenocarcinoma.
AB  - PURPOSE: Combination chemotherapy regimens can improve survival in patients with
      advanced gastric and oesophageal adenocarcinoma. Docosahexaenoic acid (DHA)
      paclitaxel is a novel conjugate formed by the covalent linkage of the fatty acid
      DHA to paclitaxel and may result in increased tumour exposure to paclitaxel
      without increased toxicity. PATIENTS AND METHODS: In this single arm, phase II
      study of DHA-paclitaxel, eligible patients with previously untreated, inoperable
      locally advanced or metastatic adenocarcinoma of the oesophagus, oesophago
      gastric junction or stomach were treated with DHA-paclitaxel (1,100 mg/m(2))
      administered by 2-h intravenous infusion every 21 days. RESULTS: Fifty-four
      patients were recruited of whom 53 were evaluable for toxicity, and 48 for
      response. There were five confirmed partial responses (9.4%) by the RECIST
      criteria. The median duration of response was 87 days (range 49-97 days), the
      median time to progression was 84 days (95% CI 78-124 days), and median overall
      survival was 262 days (95% CI 205-357 days). Grade >or=3 neutropaenia occurred in
      93% of patients, and febrile neutropaenia in 17% of patients. CONCLUSIONS: DHA
      paclitaxel has modest activity in patients with oesophago-gastric cancer and with
      haematological toxicity that is comparable to paclitaxel and docetaxel.

PMID- 17440726
TI  - Abrogation of ionizing radiation-induced G2 checkpoint and inhibition of nuclear
      export by Cryptocarya pyrones.
AB  - G(2) checkpoint inhibitors can force cells arrested in G(2) phase by DNA damage
      to enter mitosis. In this manner, several G(2) checkpoint inhibitors can enhance
      killing of cancer cells by ionizing radiation and DNA-damaging chemotherapeutic
      agents, particularly in cells lacking p53 function. All G(2) checkpoint
      inhibitors identified to date target protein phosphorylation by inhibiting
      checkpoint kinases or phosphatases. Using a phenotypic cell-based assay for G(2)
      checkpoint inhibitors, we have screened a large collection of plant extracts and
      identified Z-Cryptofolione and Cryptomoscatone D2 as highly efficacious
      inhibitors of the G(2) checkpoint. These compounds and related pyrones also
      inhibit nuclear export. Leptomycin B, a potent inhibitor of Crm1-mediated nuclear
      export, is also a very potent G(2) checkpoint inhibitor. These compounds possess
      a reactive Michael acceptor site and do not appear promising as a
      radiosensitizing agents because they are toxic to unirradiated cells at
      checkpoint inhibitory concentrations. Nevertheless, the results show that
      inhibition of nuclear export is an alternative to checkpoint kinase inhibition
      for abrogating the G(2) checkpoint and they should stimulate the search for less
      toxic nuclear export inhibitors.

PMID- 17440727
TI  - The gemcitabine, docetaxel, and capecitabine (GTX) regimen for metastatic
      pancreatic cancer: a retrospective analysis.
AB  - PURPOSE: We developed a laboratory based regimen called GTX which induces
      synergistic apoptosis in human pancreatic cancer cells. This retrospective review
      summarizes our clinical experience with GTX in an initial group of 35 patients;
      66% untreated and 34% failed prior therapies. METHODS: All patients treated with
      GTX for metastatic pancreatic cancer, prior to initiation of a prospective phase
      II trial of GTX were assessed and followed until death. GTX consisted of
      capecitabine (X), 750 mg/m(2) p.o. BID on days 1-14, gemcitabine (G) (750
      mg/m(2)) over 75 min and docetaxel (T) (30 mg/m(2)) on days 4 and 11. Thus one
      cycle of GTX was 14 days with 7 days off for a 21 day cycle. Tumor assessments
      were repeated every 3 cycles. RESULTS: All 35 patients had metastatic pancreatic
      cancer (94% liver, 6% lung sites). Grade 3-4 hematological toxicities were:
      leukopenia and thrombocytopenia-both 14%, and anemia 9%, respectively. The
      overall response rate of all 35 patients treated with GTX (from 0.5 cycles
      onward) was 29% (CR/PR) by WHO criteria, and 31% had a minor response or stable
      disease (MR, SD). At the metastatic sites for the 35 patients, there were 9%
      complete (CR) and 31% partial (PR) responses (total 40%). For the 31 patients who
      had their primary tumor (4 patients had a prior Whipple resection), there were
      13% CR and 19% PR for a response rate of 32% at the primary tumor site. Overall
      median progression free survival of responders was 6.3 months (95% C.I. 4.4-10.4
      months) and median survival was 11.2 months (95% C.I. 8.1-15.1 months). Survival
      after initiation of GTX at 12, 18, 24 and 30 months was 43, 29, 20, and 11%,
      respectively. CONCLUSION: Our retrospective review suggests that GTX has
      potential as a regimen for untreated and treated metastatic pancreatic cancer.

PMID- 17440728
TI  - Angiotensin-converting enzyme gene polymorphism in patients with psoriatic
      arthritis.
AB  - To investigate the frequency of angiotensin-converting enzyme (ACE) gene
      insertion/deletion (I/D) polymorphism genotypes in adults with psoriatic
      arthritis (PsA), a heterogeneous chronic disease with autoimmune pathology. ACE
      gene I/D polymorphism influences the plasma and tissue levels of ACE and has an
      involvement in inflammatory mechanism. The frequency of ACE gene I/D polymorphism
      genotypes was determined in 51 adults with PsA from Kuwait, and compared to that
      in 100 ethnically matched healthy controls using polymerase chain reaction. The
      distribution of ACE I/D polymorphism and allele frequencies in PsA patients were
      not significantly different from controls (P > 0.05). Further analyses of PsA
      patients showed that ACE I/D gene polymorphism was not associated with family
      history, clinical manifestations, and disease severity. However, the frequency of
      II genotype was significantly higher in patients with late disease onset than in
      those with early onset (25 vs. 3%; P = 0.04). No difference was found between the
      distribution of the ACE genotype in PsA patients and the general population in
      Kuwait. However, the presence of II genotype may confer susceptibility to the
      development of late onset PsA.

PMID- 17440729
TI  - Cost effectiveness analysis of disease modifying antirheumatic drugs in
      rheumatoid arthritis.
AB  - The objective was to assess the cost-effectiveness of various DMARDs compared
      with antimalarials (AM) for rheumatoid arthritis (RA) treatment. The data on
      disease activity, functional status and societal costs were collected from a 1
      year cohort of 152 patients with RA receiving at least one DMARD for > or = 6
      months. Incremental cost effectiveness ratio (ICER) was calculated from the
      societal costs of DMARD treatment compared with AM per one unit of HAQ
      improvement. All costs were presented in 2001 US dollars. Mean (SD) societal cost
      of AM treatment was US$ 2,285 (1,154) per patient per year. MTX + AM was less
      costly and more effective than AM, as the ICER of this combination would save US$
      834 per 1 U of HAQ improvement. MTX + SSZ, leflunomide, and triple therapy (AM +
      MTX + SSZ) were more effective than AM with additional costs. RA treatment with
      non MTX-based DMARDs was not cost-effective.

PMID- 17440730
TI  - Diagnostic efficacy of transrectal ultrasound-guided biopsy of the prostatic
      fossa in patients with rising PSA following radical prostatectomy.
AB  - To evaluate the diagnostic efficacy of transrectal ultrasound (TRUS)-guided
      biopsy of the prostatic fossa in men with biochemical relapse following radical
      retropubic prostatectomy (RP). Thirty patients, with detectable prostate specific
      antigen (PSA) and negative imaging for metastases after RP, were evaluated for
      local recurrence. All patients underwent TRUS-guided biopsies of the prostatic
      fossa, with at least six cores obtained. PSA and digital rectal examination (DRE)
      were correlated with biopsy results. Twelve patients (40%) were found with local
      recurrence. Sensitivities of TRUS and DRE were 75 and 50%, while specificities
      were 83 and 100%, respectively. Local recurrence was detected in 25% of the
      patients with PSA <or= 1 ng/ml, and higher PSA levels were correlated with an
      increased positive biopsy rate. All patients with positive DRE had positive
      biopsy and positive TRUS as well. When both TRUS and DRE were positive it was
      more likely for the patient to have positive biopsy than when both TRUS and DRE
      were negative. TRUS-guided biopsy is an efficient tool in detecting local
      recurrence after RP and should be offered to all patients with biochemical
      relapse and absence of metastatic disease irrespective of the level of PSA.

PMID- 17440731
TI  - A new and reliable culture system for superficial low-grade urothelial carcinoma
      of the bladder.
AB  - Several bladder cancer culture systems have been developed in recent years.
      However, reports about successful primary cultures of superficial urothelial
      carcinomas (UC) are sparse. Based on the specific growth requirements of UC
      described previously, we developed a new and reliable culture system for
      superficial low-grade UC. Between November 2002 and April 2006, 64 primary
      cultures of bladder cancer specimens were performed. After incubating the
      specimens overnight in 0.1% ethylenediaminetetraacetic acid solution, tumour
      cells could easily be separated from the submucosal tissue. Subsequently, cells
      were seeded in a low-calcium culture medium supplemented with 1% serum, growth
      factors, non-essential amino acids and glycine. The malignant origin of the
      cultured cells was demonstrated by spectral karyotyping. Overall culture success
      rate leading to a homogenous tumour cell population without fibroblast
      contamination was 63%. Culture success could be remarkably enhanced by the
      addition of glycine to the culture medium. Interestingly, 86.4% of pTa tumours
      were cultured successfully compared to only 50% of the pT1 and 38% of advanced
      stage tumours, respectively. G1 and G2 tumours grew significantly better than G3
      tumours (86, 73 and 41%, respectively). Up to three passages of low-grade UC
      primary cultures were possible. We describe a new and reliable culture system,
      which is highly successful for primary culture and passage of low-grade UC of the
      bladder. Therefore, this culture system can widely be used for functional
      experiments on early stage bladder cancer.

PMID- 17440732
TI  - [Granular cell tumor of the orbit].
AB  - Granular cell tumor (GCT, Abrikossoff tumor) is an extremely rare, benign tumor
      with a neurogenic origin occurring most commonly in the upper aerodigestive
      tract. GCT of the orbit is a rarity, representing a diagnostic and therapeutic
      challenge. We report on a 26 year old man suffering from unilateral ocular
      hypertension and retrobulbar pain. Exophthalmos and disturbance of motility were
      not noted by the patient. The surgical removal of the GCT, extending into the
      orbital apex, was performed by an interdisciplinary team using a combination of
      "midfacial degloving" and LeFort I-osteotomy.

PMID- 17440733
TI  - [Morning glory disc anomaly und frontonasal dysplasia].
AB  - Morning glory disc anomaly (MGDA) is a rare congenital malformation of the optic
      disc, which can be associated with midline craniofacial abnormalities, such as
      basal encephalocele. A female neonate presented with MGDA in the right eye,
      pendular nystagmus, hypertelorism, a flattened nasal root and cleft lip and
      palate. MRI revealed a basal encephalocele, agenesis of the corpus callosum and
      ventricular enlargement. MGDA combined with midline facial clefting should always
      lead to the suspicion of a basal encephalocele.

PMID- 17440734
TI  - Behavioral sterility of hybrid males in acoustically communicating grasshoppers
      (Acrididae, Gomphocerinae).
AB  - The effectiveness of hybridization barriers determines whether two species remain
      reproductively isolated when their populations come into contact. We investigated
      acoustic mating signals and associated leg movements responsible for song
      creation of hybrids between the grasshopper species Chorthippus biguttulus and C.
      brunneus to study whether and how songs of male hybrids contribute to
      reproductive isolation between these sympatrically occurring species. Songs of
      F1, F2, and backcross hybrids were intermediate between those of both parental
      species in terms phrase number and duration. In contrast, species-specific
      syllable structure within phrases was largely lost in hybrids and was produced,
      if at all, in an irregular and imperfect manner. These divergences in inheritance
      of different song parameters are likely the result of incompatibility of neuronal
      networks that control stridulatory leg movements in hybrids. It is highly
      probable that songs of hybrid males are unattractive to females of either
      parental species because they are intermediate in terms of phrase duration and
      lack a clear syllable structure. Males of various hybrid types (F1, F2, and
      backcrosses) are behaviorally sterile because their songs fail to attract mates.

PMID- 17440735
TI  - Seasonal changes in intrinsic electrophysiological activity of song control
      neurons in wild song sparrows.
AB  - Song behavior and its underlying neural substrate can change seasonally in adult
      songbirds. To test whether environmental cues induce seasonal changes in
      electrophysiological characteristics of song control neurons, we measured in
      vitro intrinsic neuronal activity in the song control nucleus RA of adult male
      song sparrows (Melospiza melodia) in both the fall non-breeding and spring
      breeding seasons. We found that RA neurons in spring-captured birds show a more
      than threefold increase in spontaneous firing rate compared to those from fall
      captured birds. We conclude that environmental cues are sufficient to induce
      seasonal changes in electrophysiological properties of song control neurons, and
      that changes in these properties may underlie seasonal changes in song behavior.

PMID- 17440736
TI  - Lumbosacral glioblastoma and leptomeningeal gliomatosis complicating the course
      of a cervicothoracic astrocytoma WHO grade II.
AB  - CASE REPORT: The reported female patient underwent sub-total resection of an
      intra-medullary cervicothoracic astrocytoma classified as WHO grade II in 1984 at
      the age of 18 months and received local irradiation. In 1989, a local recurrence
      was diagnosed and a partial resection was performed. Sixteen years later, a small
      recurrent cervicothoracic tumour was found and spinal seeding to the equine nerve
      roots and the left cerebellar cortex was apparent on MRI. The patient was
      implanted with a ventriculoperitoneal shunt for a pseudo-tumour cerebri producing
      papilloedema, which eventually lead to amaurosis. After an extended biopsy, the
      invasive lumbosacral tumour was classified as glioblastoma multiforme. Two months
      later, the patient died after rapid progression of the caudal cranial nerve
      dysfunction. DISCUSSION AND CONCLUSION: Anaplastic progression and dissemination
      of spinal astrocytomas even two decades after initial diagnosis and treatment are
      rare. Therapies and diagnostic follow-up strategies are discussed.

PMID- 17440737
TI  - Modified teniectomy. A new technique for creation of sutureless colonic
      reservoir.

PMID- 17440738
TI  - Ileus due to severe aggravation of retroperitoneal fibrosis after sigmoidectomy.

PMID- 17440739
TI  - Sulfasalazine-induced pericarditis in a patient with ulcerative colitis without
      recurrence when switching to mesalazine.
AB  - INTRODUCTION: Pericarditis is rarely reported in inflammatory bowel disease.
      Besides its common causes, pericarditis could be related to ulcerative colitis
      flare or to 5-aminosalicylic acid (5-ASA) treatment. CASE REPORT: We report the
      case of a patient in whom fever, weight loss and pericarditis developed after 16
      years of treatment with sulfasalazine for ulcerative colitis, after increasing
      the daily dosage from 1 to 3 g. DISCUSSION: The patient recovered after treatment
      discontinuation and did not exhibit any recurrence of pericarditis when treatment
      with mesalazine was introduced. CONCLUSION: In conclusion, if pericarditis occurs
      in ulcerative colitis patients treated with 5-ASA compounds, the treatment should
      be considered as a possible cause, even after an increase of the dosage. In this
      case, discontinuation of the treatment and cautious switch to another 5-ASA
      compound should be tested.

PMID- 17440740
TI  - Expression of the human phosphatases of regenerating liver (PRLs) in colonic
      adenocarcinoma and its correlation with lymph node metastasis.
AB  - BACKGROUND: Human phosphatases of regenerating liver (PRLs) can induce cell
      growth, differentiation, and malignant transformation. In this study, we used
      specific polyclonal antibodies against PRLs to investigate their expression in
      colonic adenocarcinomas and its correlation with patient gender, age, tumor
      differentiation, localization, invasion, and metastasis. MATERIALS AND METHODS:
      The polyclonal antibodies against PRL-1, PRL-2, and PRL-3 were produced and
      purified. The expression of PRLs in human colorectal carcinoma cell lines (SW480
      and SW620) was examined by Western blotting. We also examined their expression in
      normal and pathologic tissues from the human colon. The tissues included 49
      primary colonic adenocarcinomas, 14 cases with lymph node metastases, 15 colonic
      adenomas, and 12 normal colon samples. Hematoxylin and eosin staining,
      immunohistochemistry, and semiquantitative morphological analysis were used to
      evaluate the sections. RESULTS: PRLs were widely expressed in SW480 and SW620.
      PRL-1, PRL-2, and PRL-3 were expressed, respectively, in 16, 10, and 16% of
      primary colonic adenocarcinomas. In contrast, PRLs were strongly expressed in all
      lymph node metastases. There were no significant correlations between the
      expression of PRLs and patient gender, age, tumor differentiation, depth of
      invasion, or localization of tumor within the different sections of the colon.
      PRLs were not expressed in normal colon tissues or in colonic adenomas. PRLs were
      mainly expressed in the cytoplasm and at the cytoplasmic membranes of the colonic
      adenocarcinoma cells as well as in the endothelial cells and the surrounding
      smooth muscle cells of larger vessels in the lymph node metastases. CONCLUSION:
      Colonic adenocarcinoma cells have the ability to produce PRLs, which may relate
      to the lymph node metastasis of colonic adenocarcinoma.

PMID- 17440741
TI  - [Anti-CD20 therapy for inducing and maintaining remission in refractory systemic
      lupus erythematosus].
AB  - We present nine cases of systemic lupus erythematosus with refractory disease
      that we treated with the chimeric monoclonal anti-CD20 antibody rituximab. Three
      patients had renal disease, three neurological involvement with transverse
      myelitis and vasculitis of the central nervous system, one thrombocytopenia, one
      skin involvement with generalized erythema and one patient had constitutional,
      haematological and immunological symptoms. Two patients with renal disease, the
      patient with immune thrombocytopenia and the three patients with neurological
      disease, who stayed in remission despite a reduction of immunosuppressive
      therapy, responded particularly well to the therapy. Five of nine patients showed
      an improvement in ECLAM of at least two points. During therapy only minor adverse
      events were observed. One patient died during follow-up which was unrelated to
      the therapy. The selective depletion of B-lymphocytes in the therapy of systemic
      lupus erythematosus seems to be an effective and safe treatment option for
      different manifestations.

PMID- 17440742
TI  - Morphological and biochemical characterisation of sensory neurons infected in
      vitro with rabies virus.
AB  - This work was aimed at the morphological and biochemical characterisation of the
      most susceptible neuronal subpopulation to rabies virus (RABV) infection. Adult
      mouse DRG cultures were infected with RABV and double-processed for viral antigen
      detection and neuropeptides: calcitonin gene-related peptide (CGRP), galanin
      (GAL), substance P (SP), neuropeptide Y (NPY) and vasoactive intestinal peptide
      (VIP). It was found that 56% of the neurons in culture were small (diameter < 20
      microm) but, in spite of this, 69% of the infected neurons had intermediate and
      large diameters (> or = 20 microm). More than 50% of infected neurons expressed
      NPY, VIP or SP, whereas no association was found between infected neurons and the
      presence of CGRP or GAL. Despite SP having been shown to be a small neuron
      marker, it was found that RABV infects medium and large-sized SP positive cells.
      RABV preference for larger neurons could explain part of the neuropathogenesis
      since it can be suggested that, following a rabid accident, the virus uses large
      neurons (mainly innervating muscle and joints) in vivo to be transported later on
      to the central nervous system.

PMID- 17440743
TI  - MR diagnosis of meniscal tears of the knee: analysis of error patterns.
AB  - PURPOSE: Despite high accuracy of magnetic resonance imaging (MRI) for diagnosing
      meniscal tears, MR findings do not always agree with surgical findings. We
      performed a blinded, retrospective study to analyze the nature and frequency of
      errors in the MR diagnosis of meniscal tears. MATERIALS AND METHODS: Medical
      records of 100 consecutive patients who underwent MR and arthroscopy of the knee
      at our institution were reviewed. Twelve patients underwent prior meniscal
      surgery. Twenty-three patients had 27 discrepancies between MR and surgical
      findings. These were independently reviewed by two additional musculoskeletal
      radiologists in a double blinded fashion. Original incorrect diagnoses were
      categorized as either unavoidable, interpretation error or equivocal for meniscal
      tear. RESULTS: MR accuracy was 88% for the medial and 85% for the lateral
      meniscus. Of 27 incorrect MR diagnoses, 12 (44%) were unavoidable, 10 (37%)
      equivocal and 5 (19%) interpretation errors. Of the 67 medial meniscal tears, 12
      (18%) were missed. Eight (67%) of these 12 were categorized as equivocal,
      including three postoperative menisci. Of 30 lateral tears, 12 (40%) were missed,
      7 (58%) of which were categorized as unavoidable. Of these 12, 11 (92%) showed
      fraying of the inner edge, which was shaved at arthroscopy (n = 8) or had stable
      tear treated conservatively (n = 3). There were three false-positive diagnoses,
      all occuring in the lateral meniscus, two of which were unavoidable and one
      interpretation error. CONCLUSION: Of all missed lateral meniscal tears, most are
      unavoidable and related to confusion between what represents fraying and what
      represents a tear. Unavoidable false-positive diagnoses are infrequent and may be
      related to incomplete arthroscopic evaluation. Subtle or equivocal findings still
      make MR diagnosis difficult, even for experienced radiologists.

PMID- 17440744
TI  - The use of hamstrings in anterior cruciate ligament reconstruction in patients
      over 40 years.
AB  - INTRODUCTION: Anterior cruciate ligament reconstruction is an increasingly
      established method even in patients over 40 years old. Recent studies with regard
      to this procedure used BTB transplants. We did a retrospective follow-up
      examination on over-40-year-old patients with anterior cruciate ligament
      reconstruction using hamstring transplants and compared them to a younger control
      group. Our hypothesis is that functional outcome after ACL-reconstruction is
      comparable in patients under and over 40 years of age. MATERIALS AND METHODS:
      Retrospective follow-up examinations in 28 patients, 11 women and 17 men. The
      average age at the time of operation was 43.5 years (range 40-61). The average
      follow-up period was 30.4 months. Half of the patients had a femoral fixation in
      TransFix technique (Arthrex, Naples, USA), while the other 14 patients had a
      femoral bioscrew fixation (Arthrex, Naples, USA). Objectivity was ensured by
      measurements of anterior tibial translation with the rolimeter (Aircast). The
      functional outcome was determined by clinical scores (Tegner activity scale,
      Lysholm knee score, OAK score and IKDC score). The degree of arthrosis was
      defined on the basis of tunnelview radiographs and compared to the non-operated
      site. Functional results and degree of laxity was compared to a sex matched
      control group (mean age 28.0). RESULTS: The median values for the Lysholm knee
      score were 91.5 points (range 69-100), for the OAK score 93.5 points (range 67
      100) and for the IKDC score 83.35 points (range 62.1-100). For the Tegner
      activity scale values of 4.5 points (range 3-8) were obtained. In the IKDC knee
      examination form we found normal and nearly normal values in 86% and in the OAK
      examination score good and very good results in 82%. Ninety-three percent had an
      AP side-to-side difference of <5 mm in the operated knee. Subjectively, 75%
      reported that they had no feeling of instability, even when practising sport. No
      significant correlation between functional outcome and patients' age was present.
      Furthermore there were no significant differences between the investigated and
      the younger control group. The most advanced signs of arthrosis were found in the
      medial compartment of the operated side (degree A: 36%; degree B: 46%; degree C:
      14%; degree D: 4%). CONCLUSION: The predominantly good results and a high level
      of patient satisfaction show that anterior cruciate ligament reconstruction is
      justified even in over-40-year-old patients with persistend subjective
      symptomatic anterior knee instability. The indication for reconstruction should
      be based on individual factors such as level of activity or subjective feeling of
      instability rather than on a dogmatic age limit. Advanced arthrotic changes
      compared to the healthy side, might be due to a too long period of preoperative
      decision making.

PMID- 17440745
TI  - Fetal survival following posterior uterine wall rupture during labour with intact
      previous caesarean section scar.
AB  - INTRODUCTION: Posterior wall rupture of the uterus in presence of previous
      caesarean scar is an extremely rare and unpredictable event. CASE REPORT: A 26
      year old lady in her second pregnancy went into spontaneous labour at 41 weeks
      gestation. She had emergency caesarean section in her previous pregnancy. She
      made slow progress in labour to full dilatation without augmentation, but was
      noted to have fresh vaginal bleeding and breakthrough pain despite an epidural.
      Uterine scar rupture was suspected and an emergency lower segment caesarean
      section was carried out. Fresh intraperitoneal bleeding was noted but with an
      intact previous scar. The baby was delivered in good condition. A vertical
      posterior uterine wall rupture of the lower segment, 5 cm in length, was found to
      be bleeding profusely and was successfully repaired. DISCUSSION: Uterine rupture
      is a rare but serious complication. Usually the rupture occurs through the
      previous uterine scar. There are only four reported cases in the literature of
      posterior uterine rupture in labour through "healthy" uterine tissue in women
      with previous caesarean section. This is the first instance of fetal survival.
      The exact mechanism is unknown but likely to be a combination of factors
      including prostaglandin use, element of obstruction and strong inelastic scar.
      CONCLUSION: Strict vigilance is required during labour in women with previous
      scar. Early recognition of imminent scar rupture should speed delivery and
      improve the outcome for mother and baby.

PMID- 17440746
TI  - Unusual presentation of cervical cancer as advanced ovarian cancer.
AB  - BACKGROUND: Ovarian metastases from cervical cancers are uncommon. In most cases,
      the primary site of cervix is known before the occurrence of metastasis. We
      report a case of cervical adenocarcinoma presenting primarily as advanced ovarian
      cancer with the primary site totally silent. CASE REPORT: A 47-year old
      multiparous patient presented to her local hospital with vague abdominal pain for
      2 months. Initial investigations with abdominal ultrasound and computerized
      tomography scan suggested right ovarian dermoid cyst. Her CA125 was 12 micro/ml
      (0-35). Right salpingo-oophorectomy was performed with the histologic diagnosis
      of dermoid cyst. Follow-up after 5 months showed a higher level of serum CA 125
      (1,594 micro/ml) and a negative cervical smear. Exploratory laparotomy was done
      with the intent to progress to total abdominal hysterectomy, left salpingo
      oophorectomy and omentectomy with staging. Surprisingly, the histologic features
      of the specimen obtained at laparotomy were consistent with a moderately
      differentiated cervical adenocarcinoma with metastases to corpus uterus, ovaries,
      left fallopian tube, omentum and pleural cavity. The final stage was stage IV
      cervical cancer. Following this, the patient was referred to medical oncologist
      for chemotherapy. CONCLUSION: Cervical carcinoma should be suspected in any
      patient presented with bilateral ovarian tumors and positive ascitic fluid
      cytology. Negative cervical smears do not exclude the possibility of primary
      cervical carcinoma.

PMID- 17440747
TI  - Age effect on fatigue-induced limb acceleration as a consequence of high-level
      sustained submaximal contraction.
AB  - In reference to electromyographic measurement, the study was conducted to
      reassess differences in the behavior of fatigue-related neuromuscular function
      between young and elderly humans with limb acceleration (LA). Fourteen young and
      fourteen elderly subjects performed sustained index abduction at 75% of their
      maximal voluntary contractions (MVC) until task failure. Measures of
      neuromuscular function, including temporal/spectral features of muscle activity
      of the first dorsal interosseous (FDI) and LA of the index and hand, were
      monitored. The results showed a manifest fatigue-induced increase in LA of the
      index in the elderly group, but not in the young group. In contrast, only the
      young group developed a significant increase in amplitude of the electromyography
      (EMG) until task failure. Spectral analyses of LA in the index reflected marked
      age-dependent reorganization following muscle fatigue, with a greater reduction
      of relative spectral amplitude of LA in the range of 20-40 Hz, but a lesser
      reduction in coherence between EMG and LA in the elderly group. In line with
      fatigue-associated restructuring of LA, the mechanical coupling of the
      metacarpophalangeal joint was more severely undermined in the elderly group than
      in the young group. The present study manifested an age-related difference in the
      relative contributions of neural versus mechanical factors to muscle fatigue.
      Subsequent to a high-level sustained submaximal isometric contraction, a
      predominant mechanical failure of the musculotendon complex in the elderly was
      featured with LA, whereas EMG measurement characterized prevailing impairment of
      neuromuscular propagation in the young.

PMID- 17440748
TI  - Is aerobic endurance a determinant of cardiac autonomic regulation?
AB  - The aim of this study was to determine if subjects matched for VO2max but with
      differing aerobic endurance displayed similar heart rate variability (HRV) at
      rest and heart rate recovery (HRR) after maximal exercise. We hypothesized that
      the higher the aerobic endurance, the higher the HRV and the faster the HRR.
      Twenty-eight well trained middle- and long-distance runners (24 men and 4 women)
      performed a maximal continuous graded exercise test for the determination of
      maximal oxygen consumption (VO2max), ventilatory threshold (VT), peak treadmill
      velocity (PTV) and HRR, as well as a test to measure the autonomic regulation of
      heart rate during supine rest, using HRV analysis. Once both tests were
      completed, subjects were matched for VO2max and assigned to the low endurance or
      the high endurance group, depending on the %PTV at which VT occurred (81.9 +/-
      2.9 and 88.3 +/- 3.1%PTV for both groups, respectively; P < 0.0001). Contrary to
      our hypotheses, neither HRV nor HRR parameters were different between groups or
      associated with aerobic endurance. VO2max (59.0+/-7.3 ml min(-1) kg(-1)) was
      inversely correlated with ln SDNN (r = -0.44, P < 0.05), ln HF (r = -0.52, P <
      0.05), ln LF + HF (r = -0.53, P < 0.05). These results suggest that aerobic
      endurance is not associated with cardiovascular autonomic control, as measured by
      HRV and HRR.

PMID- 17440749
TI  - Identification of nestin-positive putative mammary stem cells in human
      breastmilk.
AB  - Stem cells in mammary tissue have been well characterised by using the mammary
      stem cell marker, cytokeratin (CK) 5 and the mature epithelial markers CK14, CK18
      and CK19. As these markers have never been reported in cells from breastmilk, the
      aim of this study has been to determine whether mammary stem cells are present in
      expressed human breastmilk. Cultured cells from human breastmilk were studied by
      using immunofluorescent labelling and reverse transcription/polymerase chain
      reaction (RT-PCR). We found a heterogeneous population of cells with differential
      expression of CK5, CK14, CK18 and CK19. Further, by using the multipotent stem
      cell marker, nestin, we identified cells in culture that were positive only for
      nestin or double-positive for CK5/nestin, whereas no co-staining was observed for
      CK14, CK18 and CK19 with nestin. When cells isolated from breastmilk were
      analysed by using RT-PCR prior to culture, only nestin and CK18 were detected,
      thereby indicating that breastmilk contained differentiated epithelial and
      putative stem cells. Furthermore, fluorescence-activated cell-sorting analysis
      demonstrated, in breastmilk, a small side-population of cells that excluded
      Hoechst 33342 (a key property of multipotent stem cells). When stained for
      nestin, the cells in the side-population were positive, whereas those not in the
      side-population were negative. The presence of nestin-positive putative mammary
      stem cells suggests that human breastmilk is a readily available and non-invasive
      source of putative mammary stem cells that may be useful for research into both
      mammary gland biology and more general stem cell biology.

PMID- 17440750
TI  - Vole disturbances and plant diversity in a grassland metacommunity.
AB  - We studied the disturbance associated with prairie vole burrows and its effects
      on grassland plant diversity at the patch (1 m(2)) and metacommunity (>5 ha)
      scales. We expected vole burrows to increase patch-scale plant species diversity
      by locally reducing competition for resources or creating niche opportunities
      that increase the presence of fugitive species. At the metacommunity scale, we
      expected burrows to increase resource heterogeneity and have a community
      composition distinct from the matrix. We measured resource variables and plant
      community composition in 30 paired plots representing disturbed burrows and
      undisturbed matrix patches in a cool-season grassland. Vole disturbance affected
      the mean values of nine resource variables measured and contributed more to
      resource heterogeneity in the metacommunity than matrix plots. Disturbance
      increased local plant species richness, metacommunity evenness, and the presence
      and abundance of fugitive species. To learn more about the contribution of burrow
      and matrix habitats to metacommunity diversity, we compared community similarity
      among burrow and matrix plots. Using Sorenson's similarity index, which considers
      only presence-absence data, we found no difference in community similarity among
      burrows and matrix plots. Using a proportional similarity index, which considers
      both presence-absence and relative abundance data, we found low community
      similarity among burrows. Burrows appeared to shift the identity of dominant
      species away from the species dominant in the matrix. They also allowed
      subordinate species to persist in higher abundances. The patterns we observed are
      consistent with several diversity-maintaining mechanisms, including a
      successional mosaic and alternative successional trajectories. We also found
      evidence that prairie voles may be ecosystem engineers.

PMID- 17440751
TI  - Environmental effects on sexual size dimorphism of a seed-feeding beetle.
AB  - Sexual size dimorphism is widespread in animals but varies considerably among
      species and among populations within species. Much of this variation is assumed
      to be due to variance in selection on males versus females. However,
      environmental variables could affect the development of females and males
      differently, generating variation in dimorphism. Here we use a factorial
      experimental design to simultaneously examine the effects of rearing host and
      temperature on sexual dimorphism of the seed beetle, Callosobruchus maculatus. We
      found that the sexes differed in phenotypic plasticity of body size in response
      to rearing temperature but not rearing host, creating substantial temperature
      induced variation in sexual dimorphism; females were larger than males at all
      temperatures, but the degree of this dimorphism was smallest at the lowest
      temperature. This change in dimorphism was due to a gender difference in the
      effect of temperature on growth rate and not due to sexual differences in
      plasticity of development time. Furthermore, the sex ratio (proportion males)
      decreased with decreasing temperature and became female-biased at the lowest
      temperature. This suggests that the temperature-induced change in dimorphism is
      potentially due to a change in non-random larval mortality of males versus
      females. This most important implication of this study is that rearing
      temperature can generate considerable intraspecific variation in the degree of
      sexual size dimorphism, though most studies assume that dimorphism varies little
      within species. Future studies should focus on whether sexual differences in
      phenotypic plasticity of body size are a consequence of adaptive canalization of
      one sex against environmental variation in temperature or whether they simply
      reflect a consequence of non-adaptive developmental differences between males and
      females.

PMID- 17440752
TI  - ASKyphoplan: a program for deformity planning in ankylosing spondylitis.
AB  - A closing wedge osteotomy of the lumbar spine may be considered to correct
      posture and spinal balance in progressive thoracolumbar kyphotic deformity caused
      by ankylosing spondylitis (AS). Adequate deformity planning is essential for
      reliable prediction of the effect of surgical correction of the spine on the
      sagittal balance and horizontal gaze of the patient. The effect of a spinal
      osteotomy on the horizontal gaze is equal to the osteotomy angle. However, the
      effect of a spinal osteotomy on the sagittal balance depends on both the
      correction angle and the level of osteotomy simultaneously. The relation between
      the correction angle, the level of osteotomy and the sagittal balance of the
      spine can be expressed by a mathematical equation. However, this mathematical
      equation is not easily used in daily practice. We present the computer program
      ASKyphoplan that analyses and visualizes the planning procedure for sagittal
      plane corrective osteotomies of the spine in AS. The relationship between the
      planned correction angle, level of osteotomy and sagittal balance are coupled
      into the program. The steps taken during an ASKyphoplan run are outlined, and the
      clinical application is discussed. The application of the program is illustrated
      by the analysis of the data from a patient recently treated by a lumbar osteotomy
      in AS. The software can be used free of charge on the internet at
      http://www.stega.nl under the heading "research" in the menu.

PMID- 17440753
TI  - Lumbar facet anatomy changes in spondylolysis: a comparative skeletal study.
AB  - Opinions differ as to the exact mechanism responsible for spondylolysis (SP) and
      whether individuals with specific morphological characteristics of the lumbar
      vertebral neural arch are predisposed to SP. The aim of our study was to reveal
      the association between SP and the architecture of lumbar articular facets and
      the inter-facet region. METHODS: Using a Microscribe three-dimensional apparatus
      (Immersion Co., San Jose, CA, USA), length, width and depth of all articular
      facets and all inter-facet distances in the lumbar spine (L1-L5) were measured.
      From the Hamann-Todd Human Osteological Collection (Cleveland Museum of Natural
      History, OH, USA) 120 normal male skeletons with lumbar spines in the control
      group and 115 with bilateral SP at L5 were selected. Analysis of variance was
      employed to examine the differences between spondylolytic and normal spines.
      RESULTS: Three profound differences between SP and the norm appeared: (1) in
      individuals with SP, the size and shape of L4's neural arch had significantly
      greater inter-facet widths, significantly shorter inter-facet heights and
      significantly shorter and narrower articular facets; (2) only in the L4 vertebra
      in individuals with SP was the inferior inter-facet width greater in size than
      the superior inter-facet width of the vertebra below (L5) (38.7 mm versus 40 mm);
      (3) in all lumbar vertebrae, the right inferior articular facets in individuals
      with SP were flatter compared to the control group. CONCLUSIONS: Individuals with
      L4 "SP" characteristics are at a greater risk of developing fatigue fractures in
      the form of spondylolysis at L5.

PMID- 17440754
TI  - NADH oxidase activity of rat and human liver xanthine oxidoreductase: potential
      role in superoxide production.
AB  - To characterise the NADH oxidase activity of both xanthine dehydrogenase (XD) and
      xanthine oxidase (XO) forms of rat liver xanthine oxidoreductase (XOR) and to
      evaluate the potential role of this mammalian enzyme as an O2*- source, kinetics
      and electron paramagnetic resonance (EPR) spectroscopic studies were performed. A
      steady-state kinetics study of XD showed that it catalyses NADH oxidation,
      leading to the formation of one O2*- molecule and half a H(2)O(2) molecule per
      NADH molecule, at rates 3 times those observed for XO (29.2 +/- 1.6 and 9.38 +/-
      0.31 min(-1), respectively). EPR spectra of NADH-reduced XD and XO were
      qualitatively similar, but they were quantitatively quite different. While NADH
      efficiently reduced XD, only a great excess of NADH reduced XO. In agreement with
      reductive titration data, the XD specificity constant for NADH (8.73 +/- 1.36
      microM(-1) min(-1)) was found to be higher than that of the XO specificity
      constant (1.07 +/- 0.09 microM(-1) min(-1)). It was confirmed that, for the
      reducing substrate xanthine, rat liver XD is also a better O2*- source than XO.
      These data show that the dehydrogenase form of liver XOR is, thus, intrinsically
      more efficient at generating O2*- than the oxidase form, independently of the
      reducing substrate. Most importantly, for comparative purposes, human liver XO
      activity towards NADH oxidation was also studied, and the kinetics parameters
      obtained were found to be very similar to those of the XO form of rat liver XOR,
      foreseeing potential applications of rat liver XOR as a model of the human liver
      enzyme.

PMID- 17440755
TI  - Characterization of the active site of catalytically inactive forms of [NiFe]
      hydrogenases by density functional theory.
AB  - The inactive forms, unready (Ni-A, Ni-SU) and ready (Ni-B), of NiFe hydrogenases
      are modeled by examining the possibility of hydroxo, oxo, hydroperoxo, peroxo,
      and sulfenate groups in active-site models and comparing predicted IR frequencies
      and g tensors with those of the enzyme. The best models for Ni-A and Ni-SU have
      hydroxo (mu-OH) bridges between Fe and Ni and a terminal sulfenate [Ni-S(=O)Cys]
      group, although a hydroperoxo model for Ni-A is also quite viable, whereas the
      best model for Ni-B has only a mu-OH bridge. In addition, a mechanism for the
      activation of unready hydrogenase is proposed on the basis of the relative
      stabilities of sulfenate models versus peroxide models.

PMID- 17440756
TI  - Methadone-induced Torsade de pointes after stopping lopinavir-ritonavir.

PMID- 17440757
TI  - Traumatic middle cerebral artery aneurysm: case report and review of the
      literature.
AB  - Traumatic intracranial aneurysms are rare. A case of traumatic middle cerebral
      artery aneurysm was presented. A 66-year-old man sustained a severe head injury
      in a bicycle accident. Serial computed tomography and angiography showed the
      delayed intracerebral hemorrhage caused by the traumatic middle cerebral artery
      aneurysm. The aneurysm was trapped and removed. Histological examination clearly
      revealed the pseudoaneurysm. Traumatic middle cerebral aneurysms were reviewed.

PMID- 17440758
TI  - Effect of addition of sodium alginate on bacterial cellulose production by
      Acetobacter xylinum.
AB  - Bacterial cellulose (BC) production by Acetobacter xylinum NUST4.1 was carried
      out in the shake flask and in a stirred-tank reactor by means of adding sodium
      alginate (NaAlg) into the medium. When 0.04% (w/v) NaAlg was added in the shake
      flask, BC production reached 6.0 g/l and the terminal yield of the cellulose was
      27% of the total sugar initially added, compared with 3.7 g/l and 24% in the
      control, respectively. The variation between replicates in all determinations was
      less than 5%. During the cultivation in the stirred-tank reactor, the addition of
      NaAlg changed the morphology of cellulose from the irregular clumps and fibrous
      masses entangled in the internals to discrete masses dispersing into the broth,
      which indicates that NaAlg hinders formation of large clumps of BC, and enhances
      cellulose yield. Because the structure of cellulose is changed depending on the
      culture condition such as additives, structural characteristics of BC produced in
      the NaAlg-free and NaAlg medium are compared using scanning electron microscopy
      (SEM), fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD).
      SEM photographs show some differences in reticulated structures and ribbon width
      and FT-IR spectra indicate that there is the hydrogen bonding interaction between
      BC and NaAlg, then X-ray diffraction (XRD) analysis reveals that BC produced with
      NaAlg-added has a lower crystallinity and a smaller crystalline size. The results
      show that enhanced yields and modification of cellulose structure occur in the
      presence of NaAlg.

PMID- 17440759
TI  - Anticipatory models in gaze control: a developmental model.
AB  - Infants gradually learn to predict the motion of moving targets and change from a
      strategy that mainly depends on saccades to one that depends on anticipatory
      control of smooth pursuit. A model is described that combines three types of
      mechanisms for gaze control that develops in a way similar to infants. Initially,
      gaze control is purely reactive, but as the anticipatory models become more
      accurate, the gain of the pursuit will increase and lead to a larger fraction of
      smooth eye movements. Finally, a third system learns to predict changes in target
      motion, which will lead to fast retuning of the parameters in the anticipatory
      model.

PMID- 17440760
TI  - Titratable mandibular repositioner appliances for obstructive sleep apnea
      syndrome: are they an option?
AB  - Mandibular repositioning appliances (tMRAs) designed with a titratable mechanism
      are effective to treat obstructive sleep apnea syndrome (OSAS) but are not widely
      used, although many studies have proven their value. The aim of the present study
      was to evaluate the efficacy of tMRAs in the treatment of OSAS on the criteria of
      the American Academy of Sleep Medicine (AASM; apnea/hypopnea index [AHI] < 5).
      Three hundred consecutive patients with a polysomnographic diagnosis of OSAS were
      referred for treatment with tMRAs between 2000 and 2003. Thirty-eight patients
      were excluded, and 262 concluded the titration protocol with tMRA that lasted 4
      months. After titration, the patients were referred for a medical reassessment,
      and 83 patients (70 men) participated in the new polysomnographic exam with tMRA
      in place to access tMRA's efficacy. The mean pre- and post-treatment AHI were 26
      +/- 17.7 and 4.8 +/- 5.3 events per hour, respectively (p < 0.00005). Fifty-three
      (62.6%) of the 83 patients were treated successfully (AHI < 5). Twenty-three
      patients had severe OSAS, and 12 of them (52.1%) were treated successfully (AHI <
      5). Forty patients had moderate OSAS, and 26 of them (65%) were treated
      successfully. Twenty patients had mild OSAS, and 15 (75%) were successfully
      treated. Even when applying more rigid criteria such as those of the AASM, the
      expressive success rate obtained with the treatment of different degrees of OSAS
      indicates that tMRAs are an additional valuable option even for cases of severe
      apnea in which the patient does not tolerate continuous positive airway pressure
      or cannot afford this treatment, a fact quite common in Brazil and other
      developing countries.

PMID- 17440761
TI  - Association between short sleeping hours and overweight in adolescents: results
      from a US Suburban High School survey.
AB  - Insufficient sleep may lead to adverse health effects, influencing body weight.
      This study quantified the prevalence of short sleep and the association between
      sleep duration and overweight in a sample of suburban students. Cross-sectional
      study was conducted in 2004, involving 529 students from Bay High School, Bay
      Village, OH, USA, using self-administered questionnaires assessing lifestyle and
      sleep behaviors. Students with a body mass index Z Score >85th percentile for sex
      and age were deemed overweight. Ninety percent of students reported average sleep
      time less than 8 h on school nights, with 19% reported less than 6 h of sleep per
      night. Twenty percent of the sample were overweight. Overweight was significantly
      associated with the male gender, increased caffeine consumption, and short sleep
      duration. Compared with students sleeping >8 h, the age and gender-adjusted odds
      ratio of overweight was 8.53 (95% CI: 2.26, 32.14) for those with <5 h sleep (P =
      0.0036); 2.79 (1.03, 7.55) for those with 5-6 h sleep; 2.81 (1.14, 6.91) for
      those with 6-7 h sleep; and 1.29 (0.52, 3.26) for those with 7-8 h sleep. Short
      sleep duration was common and associated with overweight with evidence of a "dose
      response" relationship. These results confirm a high prevalence of short sleep
      among suburban high school students and provide additional support suggesting
      significant association between short sleeping hours and overweight.

PMID- 17440762
TI  - Adaptive spatio-temporal filtering of disturbed ECGs: a multi-channel approach to
      heartbeat detection in smart clothing.
AB  - Intermittent disturbances are common in ECG signals recorded with smart clothing:
      this is mainly because of displacement of the electrodes over the skin. We
      evaluated a novel adaptive method for spatio-temporal filtering for heartbeat
      detection in noisy multi-channel ECGs including short signal interruptions in
      single channels. Using multi-channel database recordings (12-channel ECGs from 10
      healthy subjects), the results showed that multi-channel spatio-temporal
      filtering outperformed regular independent component analysis. We also recorded
      seven channels of ECG using a T-shirt with textile electrodes. Ten healthy
      subjects performed different sequences during a 10-min recording: resting,
      standing, flexing breast muscles, walking and pushups. Using adaptive multi
      channel filtering, the sensitivity and precision was above 97% in nine subjects.
      Adaptive multi-channel spatio-temporal filtering can be used to detect heartbeats
      in ECGs with high noise levels. One application is heartbeat detection in noisy
      ECG recordings obtained by integrated textile electrodes in smart clothing.

PMID- 17440763
TI  - Recognizing knee pathologies by classifying instantaneous screws of the six
      degrees-of-freedom knee motion.
AB  - We address the problem of knee pathology assessment by using screw theory to
      describe the knee motion and by using the screw representation of the motion as
      an input to a machine learning classifier. The flexions of knees with different
      pathologies are tracked using an optical tracking system. The instantaneous screw
      parameters which describe the transformation of the tibia with respect to the
      femur in each two successive observation is represented as the instantaneous
      screw axis of the motion given in its Plucker line coordinates along with its
      corresponding pitch. The set of instantaneous screw parameters associated with a
      particular knee with a given pathology is then identified and clustered in R(6)
      to form a "signature" of the motion for the given pathology. Sawbones model and
      two cadaver knees with different pathologies were tracked, and the resulting
      screws were used to train a classifier system. The system was then tested
      successfully with new, never-trained-before data. The classifier demonstrated a
      very high success rate in identifying the knee pathology.

PMID- 17440764
TI  - Bombesin stimulates enterocyte turnover following massive small bowel resection
      in a rat.
AB  - Recent evidence suggests that bombesin (BBS) is involved in modulation of growth
      and differentiation of normal small intestine. The purpose of the present study
      was to evaluate the effects of BBS on enterocyte turnover after massive small
      bowel resection in a rat. Male Sprague-Dawley rats were divided into three
      experimental groups: Sham rats underwent bowel transection and re-anastomosis,
      short bowel syndrome (SBS) rats underwent a 75% small bowel resection, and SBS
      BBS rats underwent bowel resection and were treated with BBS given subcutaneously
      at a dose of 20 mug/kg, once daily, from postoperative day 3 through 14.
      Parameters of intestinal adaptation (bowel and mucosal weights, mucosal DNA and
      protein, villus height and crypt depth), enterocyte proliferation and enterocyte
      apoptosis were determined in jejunum and ileum on day 15 following operation. RT
      PCR technique was used to determine Bax and Bcl-2 gene expression in ileal
      mucosa. Statistical analysis was performed using the non-parametric Kruskal
      Wallis ANOVA test, with P less than 0.05 considered statistically significant.
      Treatment with BBS resulted in a significant increase in ileal bowel and mucosal
      weight, ileal mucosal DNA and protein, jejunal and ileal villus height, jejunal
      crypt depth, and jejunal and ileal proliferation index compared to SBS-animals.
      SBS rats showed a significant increase in Bax and Bcl-2 expression in ileum that
      was accompanied by a significant increase in cell apoptosis compared to sham
      animals. SBS-BBS rats demonstrated a significant decrease in Bax and Bcl-2
      expression in ileum and a decrease in apoptotic index compared to SBS-animals. In
      conclusion, in a rat model of SBS, BBS enhances enterocyte turnover and
      stimulates structural intestinal adaptation. Decreased Bax expression may be
      responsible for the inhibitory effect of BBS on enterocyte apoptosis.

PMID- 17440765
TI  - Renal and urologic manifestations of pediatric condition falsification/Munchausen
      by proxy.
AB  - Renal and urologic problems in pediatric condition falsification (PCF)/Munchausen
      by proxy (MBP) can pose frustrating diagnostic and management problems. Five
      previously unreported victims of PCF/MBP are described. Symptoms included
      artifactual hematuria, recalcitrant urinary infections, dysfunctional voiding,
      perineal irritation, glucosuria, and "nutcracker syndrome", in addition to
      alleged sexual abuse. Falsifications included false or exaggerated history,
      specimen contamination, and induced illness. Caretakers also intentionally
      withheld appropriately prescribed treatment. Children underwent invasive
      diagnostic and surgical procedures because of the falsifications. They developed
      iatrogenic complications as well as behavioral problems stemming from their
      abuse. A PCF/MBP database was started in 1995 and includes the characteristics of
      135 PCF/MBP victims examined by the first author between 1974 and 2006. Analysis
      of the database revealed that 25% of the children had renal or urologic issues.
      They were the presenting/primary issue for five. Diagnosis of PCF/MBP was delayed
      an average of 4.5 years from symptom onset. Almost all patients were victimized
      by their mothers, and maternal health falsification and somatization were common.
      Thirty-one of 34 children had siblings who were also victimized, six of whom
      died. In conclusion, falsifications of childhood renal and urologic illness are
      relatively uncommon; however, the deceits are prolonged and tortuous. Early
      recognition and intervention might limit the harm.

PMID- 17440766
TI  - The new field of neuroskeletal biology.
AB  - The fields of neuroscience and bone biology have recently converged following the
      discovery that bone remodeling is directly regulated by the brain. This work has
      defined bone remodeling as one of the cardinal physiological functions of the
      body, subject to homeostatic regulation and integrated with the other major
      physiological functions by the hypothalamus. Central to this discovery was the
      definition of the adipocyte-derived hormone leptin as a regulator of both arms of
      bone remodeling, formation and resorption, through its action on the ventromedial
      hypothalamus and subsequently via the sympathetic nervous system to osteoblasts.
      The characterization of the sympathetic nervous system as a regulator of bone
      remodeling has led to several large clinical studies demonstrating a substantial
      protective effect of beta-blockers, particularly beta1-blockers, on fracture
      risk. Studies in model organisms have reinforced the role of the central nervous
      system in the regulation of bone remodeling in vivo by the identification of
      several additional genes, namely cocaine and amphetamine regulated transcript
      (Cart), melanocortin 4 receptor (Mc4R), neuropeptide Y (NPY), Y2 receptor,
      cannabinoid receptor CB1 (Cnbr1), and the genes of the circadian clock. These
      genes have several common features, including high levels of expression in the
      hypothalamus and the ability to regulate other major physiological functions in
      addition to bone remodeling including energy homeostasis, body weight, and
      reproduction. We review the major pathways that define the new field of
      neuroskeletal biology and identify further avenues of inquiry.

PMID- 17440767
TI  - Placement of double-J ureteric stent using the pull-through technique in patients
      with tight ureteric stenosis.
AB  - BACKGROUND: To evaluate the efficacy of antegrade insertion of the ureteric stent
      using pull-through technique in tight ureteric stricture that a guide-wire
      traversed, but a 5-F catheter could not. MATERIALS AND METHODS: Seven patients
      (M:F = 2:5, mean age 56 years) who underwent antegrade ureteric stent insertion
      using pull-through technique due to tight ureteric stricture were retrospectively
      evaluated. The strictures were due to impacted ureter stone (n = 3), metastasis
      from rectal cancer (n = 1), and idiopathic ureter stricture (n = 3). After
      failing to traverse a 5-F catheter through the stricture along the guide-wire, a
      7-F introducer sheath was inserted through the urethra. The distal end of the
      guide-wire was snared and retrieved through the urethral introducer sheath. Then
      using pull-through technique, antegrade ureteric stent insertion was performed.
      RESULTS: Double-J ureteric stent was successfully placed in all seven patients
      using the pull-through technique. Complications included abdominal/flank pain (n
      = 7), gross hematuria (n = 5) and elevated blood pressure (n = 1). All
      complications were relieved within 3 days after the procedure with conservative
      treatment. CONCLUSIONS: Antegrade double-J ureteric stent insertion using the
      pull-through technique is a safe and useful method, which can be used in tight
      ureteric strictures, where a ureteric stent cannot follow the passed guide wire.

PMID- 17440768
TI  - Role of contrast-enhanced 3D magnetic resonance portography in evaluating portal
      venous system compared with color Doppler ultrasonography.
AB  - AIM: The purpose of this study was to evaluate the capability of contrast
      enhanced three-dimensional (3D) MR portography in detecting abnormal findings
      associated with the portal venous system compared with the results of color
      Doppler ultrasonography (CDUS). MATERIALS AND METHODS: MR portography findings
      were retrospectively compared with the results of CDUS examinations in 161
      patients, who were suspected of having portal venous system abnormalities. Portal
      venous vessels were divided into main 5 groups including the main portal vein,
      its left and right intrahepatic branches, splenic vein and superior mesenteric
      vein. Imaging findings were classified as normal, occluded, or partially
      thrombosed. Results of clinical and imaging follow-up examinations including
      CDUS, MR portography or angiography, if available, were used as a proof of final
      diagnosis. The potential sites of varicose veins and collateral vessels were also
      examined by both imaging methods. RESULTS: Vascular abnormalities were identified
      in 79 of 161 patients. There was a statistically significant agreement between
      the results of MR portography and CDUS in evaluating portal venous system (kappa
      = 0.871, P < 0.05). The sensitivity of MR portography was slightly superior to
      CDUS in detecting partially thrombosis and occlusion in the main portal venous
      vessels. In addition, MR portograms were superior to CDUS in the management of
      patients with portal hypertension by identifying portosystemic collaterals more
      adequately, and clearly demonstrated portal venous vessels that cannot be
      visualized at CDUS. CONCLUSION: Results of present study indicates that contrast
      enhanced 3D MR portography is well suited and superior to CDUS in the management
      of patients with portal hypertension.

PMID- 17440769
TI  - Ancient schwannoma of the female pelvis.
AB  - BACKGROUND: The objective of this article is to define the imaging
      characteristics of ancient schwannoma, which is a rare variant of benign
      schwannoma with degenerative changes, arising in the female pelvis simulating
      ovarian tumors. METHODS: Eleven surgically proven ancient schwannomas of the
      female pelvis were evaluated retrospectively on the basis of CT and MR findings.
      RESULTS: Typical intra-pelvic schwannoma was a neurologically asymptomatic large
      mass, which may situate at presacral or lateral pelvic region with the continuity
      to the nerve or neural foramen. Ancient schwannomas manifested as encapsulated
      solid masses with random or eccentric cystic areas, or as cystic masses with
      marginal crescent-shaped or nodular solid components. Hemorrhagic changes and
      calcifications were often observed on MRI and CT respectively. To detect
      ipsilateral normal ovary and to demonstrate centripetal displacement of the
      adjacent rectum or iliac vessels were helpful to diagnose the tumor as an extra
      ovarian mass situated at the extraperitoneal region. CONCLUSIONS: Diagnosis of
      ancient schwannoma before surgical treatment is important and should be made by
      its characteristic clinical and imaging findings.

PMID- 17440770
TI  - Virtual CT thoracoscopy: preoperative simulation for thoracoscopic surgery of
      esophageal cancer.
AB  - Thoracoscopic esophageal surgery is a complex procedure requiring simultaneous
      dissection of the esophagus and lymph nodes while maintaining the surrounding
      vessels. Because of the difficulty in obtaining comprehensive views of the
      operative field, three-dimensional (3-D) images with preoperative information on
      the vascular system, esophagus, trachea, lungs, lymph nodes, skin, and bones
      would be extremely helpful in performing the surgery.

PMID- 17440771
TI  - Chronic viral hepatitis and hepatocellular carcinoma.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of death
      from malignancy worldwide, and its increasing incidence parallels rising global
      rates of hepatitis B (HBV) and hepatitis C (HCV). METHODS: This retrospective
      review was undertaken to identify differences in the epidemiology and tumor
      characteristics of 255 patients with HCC due to chronic HBV (n = 105) or HCV (n =
      150). RESULTS: Hepatitis B patients were predominantly Asian (84%), whereas HCV
      patients were predominantly Caucasian (72%; p < 0.0001). Hepatitis B patients
      exhibited stronger family histories of liver disease (54%) and HCC (33%), whereas
      HCV risk factors included blood transfusion (56%), intravenous drug abuse (31%),
      and alcohol consumption (44%; p < 0.0001 for all comparisons). Pretreatment
      laboratory values showed lower albumin and platelet levels but higher bilirubin
      and AST levels in HCV versus HBV patients (p < 0.0001 to 0.01). As cirrhosis was
      present in nearly all HCV patients, but only in 79% of HBV patients, HCV patients
      had more stigmata of portal hypertension, including ascites (65%), varices (86%),
      splenomegaly (77%), and encephalopathy (41%; p < 0.0002 for all comparisons).
      Although tumors in HBV patients were larger (7.3 cm versus 5.1 cm; p = 0.0001)
      and more frequently bilobar, the tumor grade, number of tumors, and metastases
      were similar for both groups. Hepatitis C patients received less treatment,
      including chemoembolization and surgical resection. The 5-year survival was
      higher in HBV patients compared to HCV patients (56% versus 36%, p = 0.046).
      CONCLUSIONS: Patients with HBV- and HCV-related HCC have different epidemiologic,
      clinical, and survival characteristics. More HCV patients presented with advanced
      cirrhosis, received less aggressive treatment, and experienced lower 5-year
      survival.

PMID- 17440773
TI  - One-step surgery for breast cancer: back to the future?

PMID- 17440774
TI  - Impact of preoperative planning using virtual segmental volumetry on liver
      resection for hepatocellular carcinoma.
AB  - BACKGROUND: Accurate assessment of resection volume and vascular anatomy is
      mandatory in preoperative planning for safe and curative hepatectomy to treat
      cancer. Accordingly, we examined feasibility and accuracy of a preoperative three
      dimensional (3D) computed tomography (CT) scan based simulation in patients with
      impaired liver function undergoing hepatectomy for hepatocellular carcinoma
      (HCC). METHODS: Hepatectomy simulation software was programmed to reconstruct
      detailed 3D vascular structure and calculate liver volume based on hepatic
      circulation. In 113 patients with HCC, liver resection volume was estimated
      preoperatively by both simulation and conventional planimetry. For validation,
      predicted resection volumes were compared with actual resected specimen weights.
      The resection margin as estimated by the simulation was compared with the margin
      in the specimen. RESULTS: Simulation showed higher correlation and smaller
      discrepancy (r = 0.96; 9.3 ml) between predicted and actual liver resection
      volume than conventional planimetry (r = 0.74; 174 ml). Simulation showed
      correlation (p < 0.01) between estimated and actual segmental volume, which was
      not measurable by planimetry. Simulation showed a correlation (r = 0.84) between
      predicted and actual margin, with a difference of 1.6 mm. CONCLUSIONS:
      Hepatectomy simulation in 3D predicted segmental liver volume and the resection
      margin accurately. This virtual method should contribute to preoperative planning
      to achieve safe, curative resection in HCC patients, whose hepatic function is
      compromised.

PMID- 17440775
TI  - Normal swallowing and functional magnetic resonance imaging: a systematic review.
AB  - Unknowns about the neurophysiology of normal and disordered swallowing have
      stimulated exciting and important research questions. Previously, these questions
      were answered using clinical and animal studies. However, recent technologic
      advances have moved brain-imaging techniques such as functional magnetic
      resonance imaging (fMRI) to the forefront of swallowing neurophysiology research.
      This systematic review has summarized the methods and results of studies of
      swallowing neurophysiology of healthy adults using fMRI. A comprehensive
      electronic and hand search for original research was conducted, including few
      search limitations to yield the maximum possible number of relevant studies. The
      participants, study design, tasks, and brain image acquisition were reviewed and
      the results indicate that the primary motor and sensory areas were most
      consistently active in the healthy adult participants across the relevant
      studies. Other prevalent areas of activation included the anterior cingulate
      cortex and insular cortex. Review limitations and suggested future directions are
      also discussed.

PMID- 17440776
TI  - Preliminary investigation of swallowing apnea duration and swallow/respiratory
      phase relationships in individuals with cerebral vascular accident.
AB  - Swallowing apnea duration (SAD) and swallow-respiratory phase relationships were
      examined in individuals with cerebral vascular accident (CVA) and dysphagia who
      aspirated (n=11) and did not aspirate (n=15). Simultaneous videofluoroscopic and
      respiratory measures were recorded across 5-, 10-, 15-, and 20-ml thin and thick
      liquid bolus trials. These data were also compared with that previously acquired
      with healthy older adults (n=20). A moderate amount of systematic missing data
      was evidenced in the individuals who were dysphagic and especially those who
      aspirated subsequently limiting inferential analyses. Only 1 of the 11
      participants who aspirated and 7 of the 15 who did not aspirate completed all 16
      conditions. Six of the remaining ten who aspirated had missing data subsequent to
      termination of trials due to aspiration risk. The remaining four and seven of the
      eight who did not aspirate had missing data due to poor respiratory waveforms.
      From the remaining data, it was found that SAD and respiratory phase
      relationships differed among individuals with dysphagia and CVA (i.e., those who
      aspirate vs. those who do not aspirate) and healthy older adults. SAD was found
      to be longer for those who aspirated versus those who did not for all bolus
      viscosities and volumes with the exception of thick-liquid 10-ml boluses. In
      addition, SAD from those that aspirated was twice as long as that found in
      healthy older adults for all conditions. Regarding respiratory phase
      relationships, there was a difference between the proportions of respiratory
      patterns in those who aspirated versus those who did not. Those who aspirated
      demonstrated a markedly greater percentage of swallows that interrupted
      inhalation. In addition, the inhale-swallow-inhale pattern occurred with a
      greater frequency as swallowing severity increased. Healthy older adults, those
      who did not aspirate, and those who aspirated used the inhale-swallow-inhale
      pattern 0.1%, 3.0%, and 9.0%, respectively.

PMID- 17440777
TI  - Risks of oral sodium phosphate for pre-colonoscopy bowel preparation in children.

PMID- 17440778
TI  - Cervical scarless endoscopic thyroidectomy: Axillo-bilateral-breast approach
      (ABBA).
AB  - BACKGROUND: Neck surgery is one of the latest applications of minimally invasive
      surgery. We applied a new technique for totally endoscopic thyroidectomy, the
      axillo-bilateral-breast approach (ABBA). This approach does not leave a scar on
      the neck. METHODS: Between February 2005 and October 2005, 13 patients were
      treated by ABBA for uni- or multinodular goitres. Surgery is performed under
      general anaesthesia and in supine position. 5 mm bilateral skin incisions are
      made on the margin of the areola of nipple. They are used to insert and
      subcutaneously push forward a 20 cm long, 5 mm trocar to the jugular fossa. A
      further 5 mm incision is performed in the right axilla. The right breast trocar
      is the optical trocar. A Maryland clamp in axillary position and 5 mm harmonic
      scalpel via the left breast trocar permit a clear view of the further subfascial
      preparation. The caudal hyoidal muscles are longitudinally split along the linea
      alba. Using delicate blunt dissection, both thyroid lobes are exposed. After
      isthmus transection is performed, the upper thyroid pole is being mobilized. The
      upper pole vessels are isolated and divided close to the thyroid capsule.
      Preparation of the retrothyroidal area includes visualization of the recurrent
      laryngeal nerve. The resection is performed without bleeding with a harmonic
      scalpel. Via the axillary approach, with the incision being widened, a 20 mm
      trocar is inserted and advanced up to the thyroid lodge to remove the specimen.
      RESULTS: The average operation time was 132 minutes. No patient had to be
      converted to a conventional approach. Hypocalcaemia or recurrent laryngeal nerve
      palsy were not observed postoperatively. CONCLUSION: Our preliminary results show
      that the ABBA technique is a feasible, safe procedure with excellent cosmetic
      benefits. The small scars in the right axilla and bilateral nipple areola are
      almost invisible.

PMID- 17440779
TI  - Comments on: laparoscopically assisted reversal of Hartmann's procedure.

PMID- 17440780
TI  - Retrievable inferior vena cava filters may be safely applied in gastric bypass
      surgery.
AB  - INTRODUCTION: Pulmonary embolus (PE) is a potentially devastating and fatal
      postoperative complication in morbidly obese patients. This study was undertaken
      to review the safety and efficacy of retrievable prophylactic inferior vena cava
      (IVC) filters in high-risk morbidly obese patients undergoing gastric bypass.
      METHODS: Patients who underwent gastric bypass surgery and preoperative insertion
      of retrievable IVC filters had their records reviewed. Indications for IVC filter
      insertion were: history of deep venous thrombosis (DVT) or PE, long-standing
      sleep apnea, venous stasis disease, and/or weight > 400 pounds. RESULTS: 24
      patients underwent IVC filter placement before gastric bypass surgery. There were
      10 women and 14 men with an average age of 50 +/- 6.3 years (range 39 to 59) and
      average body mass index (BMI) of 57 +/- 7.5 kg/m(2) (range 49 to 74). BMI greater
      then 50 kg/m(2) was present in 21 of 24 patients (88%). All patients had
      successful IVC filter placement. IVC filter retrieval postoperatively was
      performed in 20 of 24 patients (83%) with three left for clinical reasons and one
      (4%) left due to technical inability to retrieve. There was one complication
      directly attributable to IVC filter retrieval. There were no deaths. Five
      patients (21%) developed DVT or PE postoperatively. Follow-up was 16 +/- 7.6
      months (range 8 to 33). CONCLUSIONS: Prophylactic IVC filter placement and
      retrieval can be safely undertaken in high-risk gastric bypass patients. We
      recommend preoperative IVC filter placement in selected patients.

PMID- 17440781
TI  - The impact of objective assessment and constructive feedback on improvement of
      laparoscopic performance in the operating room.
AB  - OBJECTIVES: The study was carried out to demonstrate the impact of assessment and
      constructive feedback on improvement of laparoscopic performance in the operating
      room (OR). DESIGN: Sixteen surgical trainees performed a laparoscopic
      cholecystectomy in the OR. The participants were then divided into two groups.
      The procedure performed by group 1 was assessed by an experienced surgeon, and
      detailed and constructive feedback was provided to each trainee. Group 2 received
      no feedback. Subsequently, all subjects performed a new laparoscopic
      cholecystectomy in the OR. Both operative procedures were recorded on videotapes
      and assessed by two independent and blinded observers using a validated scoring
      system. MAIN OUTCOME MEASURES: Error and economy of movements score assessed
      during the laparoscopic procedures in the OR. RESULTS: No differences in baseline
      assessments were found between the two groups (t-test, p > 0.5). Surgeons, who
      received feedback (group 1) made significantly greater improvement in their time
      to complete the following procedure (independent sample t-test, p = 0.022), error
      (t-test, p = 0.003) and economy of movement scores (t-test, p < 0.001).
      CONCLUSIONS: Surgeons who received constructive feedback made significantly
      greater improvement in their performance in the OR compared with those in the
      control group. The study provides objective evidence that assessment is
      beneficial for surgical training and should be implemented in the educational
      programmes in the future.

PMID- 17440782
TI  - Optimizing recovery after laparoscopic colon surgery (ORAL-CS): effect of
      intravenous ketorolac on length of hospital stay.
AB  - BACKGROUND: The objective of this study was to determine if intravenous ketorolac
      can reduce ileus following laparoscopic colorectal surgery, thus shortening
      hospital stay. METHODS: This was a prospective, randomized, double-blind, placebo
      controlled, clinical trial of patients undergoing laparoscopic colorectal
      resection and receiving morphine patient controlled analgesia (PCA) and either
      intravenous ketorolac (group A) or placebo (group B), for 48 h after surgery.
      Daily assessments were made by a blinded assistant for level of pain control.
      Diet advancement and discharge were decided according to strictly defined
      criteria. RESULTS: From October 2002 to March 2005, 190 patients underwent
      laparoscopic colorectal surgery. Of this total, 84 patients were eligible for
      this study and 70 consented. Another 26 patients were excluded, leaving 22
      patients in each group. Two patients who suffered anastomotic leaks in the early
      postoperative period were excluded from further analysis. Median length of stay
      for the entire study was 4.0 days, with significant correlation between
      milligrams of morphine consumed and time to first flatus (r = 0.422, p = 0.005),
      full diet (r = 0.522, p < 0.001), and discharge (r = 0.437, p = 0.004). There we
      no differences between groups in age, body mass index, or operating time.
      Patients in group A consumed less morphine (33 +/- 31 mg versus 63 +/- 41 mg, p =
      0.011), and had less time to first flatus (median 2.0 days versus 3.0 days, p <
      0.001) and full diet (median 2.5 days versus 3.0 days, p = 0.033). The reduction
      in length of stay was not significant (mean 3.6 days versus 4.5 days, median 4.0
      days versus 4.0 days, p = 0.142). Pain control was superior in group A. Three
      patients required readmission for treatment of five anastomotic leaks (4 in group
      A versus 1 in group B, p = 0.15). Two of them underwent reoperation. CONCLUSIONS:
      Intravenous ketorolac was efficacious in improving pain control and reducing
      postoperative ileus when anastomotic leaks were excluded. This simple
      intervention shows promise in reducing hospital stay, although the outcome was
      not statistically significant. The high number of leaks is inconsistent with this
      group's experience and is of concern.

PMID- 17440783
TI  - Initial experience with a novel endoscopic device allowing intragastric
      manipulation and plication.
AB  - BACKGROUND: Current developments in intraluminal and transluminal natural orifice
      surgery are limited by issues of access, tissue manipulation, and secure tissue
      approximation/closure. This report describes an initial laboratory experience
      with a novel tissue approximation and suturing device. The device is deployed via
      a previously described platform and is 6 mm in diameter. Desirable qualities of
      this tissue approximation/closure device include robust tissue grasping, minimal
      tissue trauma, fully visualized anchor placement via off-axis needle and anchor
      deployment, full reloadability without instrument withdrawal, single-operator
      operating capability, torque-stable manipulability, and operator-controlled
      tension setting of tissue anchor pairs. METHOD: The device was trialed in
      performing several maneuvers in porcine or canine models. The features of the
      system allowed bimanual tissue manipulation, full-thickness tissue approximation
      and plication, and secure closure of an ex vivo gastrotomy hole similar to that
      used during transluminal surgical interventions. CONCLUSIONS: This device appears
      to offer promise in achieving more complex endoluminal and potentially
      transluminal tasks, including secure suture closure of tissue defects and access
      holes. As such, devices of this type may prove useful in addressing some of the
      identified barriers to further development of natural orifice surgical
      intervention. Further investigation of the qualities and capabilities of this
      device in these settings is warranted.

PMID- 17440784
TI  - Outcomes promote reoperative Heller myotomy for symptoms of achalasia.
AB  - BACKGROUND: Heller myotomy is accepted as first-line therapy for achalasia, yet
      for a small number of patients, symptoms persist or recur after myotomy. This
      study was undertaken to report our results with reoperative laparoscopic Heller
      myotomy for recurrent symptoms of achalasia. METHODS: We have undertaken
      laparoscopic Heller myotomy in 275 patients and reoperative myotomy in 12
      patients for recurrent dysphagia, of which three had their initial myotomy
      undertaken by us. For each, studies prior to reoperative Heller myotomy
      documented a nonrelaxing lower esophageal sphincter without stricture. Patients
      scored symptoms before and after reoperative myotomy. RESULTS: Before reoperative
      myotomy, 75% underwent dilation and 42% underwent Botox injection. Ten of twelve
      reoperative myotomies were undertaken and completed laparoscopically. Median
      follow-up is 24.1 months (29.0 months + 25.89). Symptom frequency and severity
      scores improved significantly after reoperative myotomy. Frequency of vomiting
      and frequency and severity of heartburn were improved after reoperative myotomy,
      but not to a significant extent. However, they were not particularly notable
      prior to surgery, compared to obstructive symptoms, such as dysphagia. Excellent
      or good outcomes were reported in 73%, and notably, 91% stated that they would
      have the operation again after having been through the process firsthand and
      knowing their outcomes. CONCLUSION: Patient outcomes promote the application of
      reoperative Heller myotomy for recurrent or persistent symptoms of achalasia
      following Heller myotomy.

PMID- 17440785
TI  - Systematic review on safety and efficacy of repeat hepatectomy for recurrent
      liver metastases from colorectal carcinoma.
AB  - BACKGROUND: We critically appraised the quantity and quality of current clinical
      evidence to demonstrate the efficacy and safety of repeat hepatectomy for
      recurrent colorectal liver metastases (CRLM). METHODS: Electronic searches for
      relevant studies published in peer-reviewed medical journals on repeat
      hepatectomy for recurrent CRLM before January 2007 were performed on six
      databases. The quality of each included study was independently assessed.
      Clinical effectiveness was synthesized through a narrative review with full
      tabulation of results of all included studies. RESULTS: Seventeen studies with
      more than 20 patients were included for quality appraisal and data extraction.
      All 17 included articles were observational cases series. The overall
      perioperative morbidity rate ranged from 7% to 30% and mortality rate varied from
      0% to 5%. The overall median survival since the repeat hepatectomy ranged from 23
      to 56 months, with 3- and 5-year survival of 24% to 68% and 21% to 49%,
      respectively. The median disease-free survival ranged from 9 to 52 months, with 3
      and 5-year disease-free survival of 16% to 68% and 16% to 48%, respectively.
      CONCLUSIONS: The current literature suggests that repeat hepatectomy is
      associated with a prolonged survival for recurrent CRLM and is justified in
      selected patients because there is a lack of evidence for effective alternative
      treatments.

PMID- 17440786
TI  - Voxel-based NK1 receptor occupancy measurements with [(18)F]SPA-RQ and positron
      emission tomography: a procedure for assessing errors from image reconstruction
      and physiological modeling.
AB  - PURPOSE: Receptor occupancy studies with positron emission tomography (PET) are
      widely used as aids in the drug development process. This study introduces a
      general procedure for assessing errors that arise from the applied image
      processing methods in PET receptor occupancy studies using the neurokinin-1 (NK1)
      receptor occupancy study as an example. PROCEDURES: The bias and variance among
      eight combinations of image reconstruction and model calculation methods for
      estimating voxel-level receptor occupancy results were examined. The tests were
      performed using a dynamic numerical phantom based on a previous PET drug
      occupancy study with the NK1 receptor antagonist tracer [(18)F]SPA-RQ. RESULTS:
      The simplified reference tissue model with basis functions (SRTM BF) was best at
      estimating receptor occupancy in terms of average bias. On the other hand, median
      root prior (MRP) image reconstruction produced the lowest variances in the
      occupancy estimates. These results suggest that SRTM BF and MRP is, in this case,
      the combination of choice in voxel-based receptor occupancy calculation. In the
      calculation of regional binding potential values, the commonly used sample mean
      is not applicable and, e.g., the median could be used instead. CONCLUSIONS: This
      study shows that even this kind of complicated receptor study can be
      statistically evaluated. The reconstruction methods had an effect on the variance
      in the voxel-based receptor occupancy calculation. The model calculation methods
      influenced the average bias. The test method was found useful in assessing the
      methodological sources of systematic and random error in receptor occupancy
      estimation with PET.

PMID- 17440787
TI  - Fast track--different implications in pancreatic surgery.
AB  - Concepts in "fast-track" surgery, which provide optimal perioperative care, have
      been proven to significantly reduce complication rates and decrease hospital
      stay. This study explores whether fast-track concepts can also be safely applied
      and improve the outcomes of major pancreatic resections. Perioperative data from
      255 consecutive patients, who underwent pancreatic resection by means of fast
      track surgery in a high-volume medical center, were analyzed using univariate and
      multivariate models. Of the 255 patients, 180 received a pancreatic head
      resection and 51 received distal, 15 received total, and 9 received segmental
      pancreatectomies. The patients were discharged on median day 10 with a 30-day
      readmission rate of 3.5%. The in-hospital mortality was 2%, whereas medical and
      surgical morbidities were 17 and 25%, respectively. Fast-track parameters, such
      as first stools, normal food, complete mobilization, and return to normal ward,
      correlated significantly with early discharge (p < 0.05). Patients' age,
      operation time, and early extubation proved to be independent factors of early
      discharge, shown through multivariate analysis (odds ratio: 4.0, 2.0, and 2.8,
      respectively; p < 0.05). Low readmission, mortality, and morbidity rates
      demonstrate that fast-track surgery is in fact feasible and safe and promotes
      earlier discharge without compromising patient outcomes.

PMID- 17440788
TI  - Duodenal-content reflux into the esophagus leads to expression of Cdx2 and Muc2
      in areas of squamous epithelium in rats.
AB  - The molecular events responsible for the transdifferentiation of epithelial cells
      of the esophagus to a columnar cell type are not well understood. Cdx2 has been
      detected in Barrett's esophagus, so we sought evidence of Cdx2 expression during
      the process of transdifferentiation of the esophageal squamous epithelium into a
      glandular phenotype. Thirty-two rats underwent an esophago-jejunostomy to produce
      esophagitis of 20, 25, 30, or 35 weeks of duration. The spectrum of esophageal
      lesions induced by chronic reflux was examined for expression of Cdx2 and Muc2 by
      immunohistochemistry. Five animals developed glandular metaplasia and
      adenosquamous carcinoma, two developed only glandular metaplasia, and two had
      adenosquamous carcinoma alone. Nuclear Cdx2 expression was detected in 57% (four
      of seven) and 43% (three of seven) of foci of glandular metaplasia and
      adenosquamous carcinomas, respectively. Cdx2 staining was detectable in some
      squamous and some mucus secreting cells. Perinuclear and perivacuolar staining of
      Muc2 was detected focally in 71% (five of seven) and 57% (four of seven) of areas
      with glandular metaplasia and adenosquamous carcinoma, respectively. We show that
      duodenal-content reflux into the esophagus switches on the expression of Cdx2
      protein in esophageal keratinocytic cells, promoting a mucinous
      transdifferentiation process with secretion of intestinal mucin Muc2.

PMID- 17440789
TI  - Resected serous cystic neoplasms of the pancreas: a review of 158 patients with
      recommendations for treatment.
AB  - BACKGROUND: Serous cystic neoplasms of the pancreas are regarded as a benign
      entity with rare malignant potential. Surgical resection is generally considered
      curative. OBJECTIVE: To perform the largest single institution review of patients
      who underwent surgical resection for serous cystic neoplasms of the pancreas in
      the hopes of guiding future management. METHODS: Between June 1988 and January
      2005, 158 patients with serous cystic neoplasms of the pancreas underwent
      surgical resection. A retrospective analysis was performed. Univariate and
      multivariate models were used to determine factors influencing perioperative
      morbidity and mortality. Major complications were defined as pancreatic fistula
      or anastomotic leak, postoperative bleed, retained operative material, or death.
      Minor complications were defined as wound infection, postoperative
      obstruction/ileus requiring total parenteral nutrition (TPN), delayed gastric
      emptying, arrhythmia, or other infection. RESULTS: The mean age of the patients
      was 62.1 years, with 75% being female. The majority of patients were symptomatic
      at presentation (63%), with abdominal pain as the most common symptom. Of the 158
      patients, 75 underwent distal pancreatectomy, 65 underwent
      pancreaticoduodenectomy, nine underwent central pancreatectomy, five underwent
      local resection or enucleation, and four underwent total pancreatectomy. Mean
      tumor diameter was 5.1 cm. Mean operative time was 277 min. Mean postoperative
      length of hospital stay was 11 days. One patient was diagnosed at presentation
      with serous cystadenocarcinoma. The remaining 157 patients were initially
      diagnosed with benign serous cystadenoma. One of three patients with locally
      aggressive benign disease later presented with metastatic disease. Resection
      margins for all 158 patients were negative for tumor, and only one (0.6%) showed
      lymph node involvement. There was one intraoperative death. The incidence of
      major perioperative complications was 18%, whereas the incidence of minor
      complications was 33%. Men were significantly more likely to experience minor
      perioperative complications (OR = 3.74, P = 0.008), whereas patients greater than
      65 years showed a trend toward fewer major complications (OR = 0.36, P = 0.09).
      CONCLUSIONS: Surgically resected serous cystic neoplasms of the pancreas are
      typically seen in asymptomatic women as 5 cm neoplasms and are predominantly
      benign. Most are resected via either a left- or right-sided pancreatectomy with
      low mortality risk, but with notable major or minor morbidity. Cystadenocarcinoma
      is a rare finding on initial resection of serous cystic neoplasms. However,
      initial pathology specimens exhibiting benign but locally aggressive neoplasia
      may indicate an increased likelihood of recurrence or metachronous metastasis,
      although this claim is limited by a small patient subpopulation in this study and
      warrants further review.

PMID- 17440790
TI  - A prospective evaluation of an algorithm incorporating routine preoperative
      endoscopic ultrasound-guided fine needle aspiration in suspected pancreatic
      cancer.
AB  - BACKGROUND: Whether tissue diagnosis is required in the preoperative evaluation
      of patients with suspected pancreatic cancer remains controversial. We
      prospectively evaluated the accuracy, safety, and potential impact on surgical
      intervention of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in
      the preoperative evaluation of suspected pancreatic cancer. METHODS: All patients
      who underwent EUS-FNA at our institution (n = 547) over a 4.5-year period were
      enrolled. Patients underwent surgical exploration and resection based on their
      comorbidity status, evidence of resectability based on spiral computed tomography
      (CT) and EUS imaging reviewed in a multidisciplinary approach. RESULTS: Of 547
      patients enrolled (median age 64 years, 60% male), 49% presented with obstructive
      jaundice. The operating characteristics of EUS-FNA of solid pancreatic masses
      were: sensitivity 95% (95% CI: 93.2-95.4), specificity 92% (95% CI: 86.6-95.7),
      positive predictive value 98% (95% CI: 97-99), negative predictive value 80% (95%
      CI: 74.9-82.7). The overall accuracy of EUS-FNA was 94.1% (95% CI: 92.0-94). Of
      the 414 true positive patients by EUS-FNA, 138 (33%) were explored. Of patients
      deemed operable by combined imaging, 42% had surgical resection. Eighty-two
      percent of true positive patients were ultimately found inoperable and received
      palliative therapy or chemotherapy. Of the 94 patients with true negative
      cytology based on extended follow-up, only 7 (7%) underwent surgical resection.
      Of those with false negative diagnoses (n = 24), 5 patients underwent
      exploration/resection based on detection of mass lesions by EUS. The remaining
      patients had unresectable disease. Mild self-limiting pancreatitis occurred in
      (0.91%). CONCLUSIONS: EUS-FNA is a safe and highly accurate method for tissue
      diagnosis in suspected pancreatic cancer. This approach allows for preoperative
      counseling of patients, minimizing surgeon's operative time in cases of
      unresectable disease, and avoids surgical biopsies in the majority of patients
      with inoperable disease. In addition, it allows for conservative management of
      patients with benign biopsies. We still, however, recommend exploration of
      patients with clinical scenario suspicious for pancreatic cancer, a mass found on
      EUS or CT, but inconclusive or negative cytology.

PMID- 17440791
TI  - Portal vein interposition using homologous iliac vein graft during extensive
      resection for hilar bile duct cancer.
AB  - Although autologous vein grafts have been used for portal vein (PV)
      reconstruction after long-segment portal vein resection during surgery for hilar
      bile duct cancer, their procurement prolongs operation time and increases
      morbidity. Less is known regarding the use of homologous vein grafts. The
      feasibility of homografts for PV reconstruction was preliminarily evaluated in
      two patients who underwent curative resection for hilar cholangiocarcinoma. Both
      patients underwent left lobectomy, caudate lobectomy, bile duct resection, and
      segmental PV resection and interposition vein graft reconstruction. The iliac
      vein homografts were obtained from deceased organ donors and stored for 1-2 days
      in cold preservation solution without freezing. Neither immunosuppression nor
      anticoagulation was attempted. One patient has shown good PV patency for 27
      months. The second patient, who had received adjuvant chemoradiotherapy, showed
      an asymptomatic waisting at the proximal PV anastomosis site after 4 months,
      which was relieved by percutaneous balloon dilatation, and has been doing well
      for 12 months. In conclusion, our preliminary experience with these two patients
      suggests that cold-stored iliac vein homografts can be considered as PV
      substitutes after long PV segment resection during extensive hepatobiliary
      surgery.

PMID- 17440792
TI  - Enterocolitis due to simultaneous infection with rotavirus and Clostridium
      difficile in adult and pediatric solid organ transplantation.
AB  - Diarrhea is a well-known complication of immunosuppression but is also frequently
      caused by pathogens such as Clostridium difficile (CD) and rotavirus (RV). Three
      adult and five pediatric solid organ recipients (SORs) developed diarrhea with
      simultaneous identification of CD and RV. Rotavirus was identified using an
      immunochromatografic- or enzyme-linked immunosorbent assay; CD was identified
      using a rapid immunoassay or enzyme immunoassay. One adult renal, one adult
      kidney-pancreas, one adult liver, and five pediatric liver recipients were
      affected. Onset of RV/CD infection ranged from 2 weeks to 4 years posttransplant.
      All patients presented with enterocolitis causing significant fluid and
      electrolyte loss. In adults, CD was treated with metronidazole and in children
      with oral vancomycin. RV infection was treated with fluid/electrolyte
      replacement. During diarrhea, a significant rise in tacrolimus serum level was
      noted. All patients cleared CD. One child developed recurrent episodes of RV
      infection and died from bacterial sepsis; the renal recipient died 6 months
      posttransplant from myocardial infarction. The remaining six patients are
      currently alive with well-functioning grafts. Simultaneous infection with CD and
      RV may lead to severe diarrhea in SORs. Both pathogens should be considered in
      SOR presenting with diarrhea.

PMID- 17440793
TI  - Hernia sac laparoscopy under spinal anesthesia for evaluation of reduced
      incarcerated inguinal hernia.
AB  - Hernia sac laparoscopy (laparoscopy through an inguinal hernia sac) is a useful
      method to evaluate the viability of the self-reduced bowel of incarcerated
      inguinal hernia that is suspected for strangulation, and avoid unnecessary
      exploratory laparotomy. On the other hand, peritoneal insufflation for
      laparoscopy is best avoided in patients with severe chronic obstructive pulmonary
      disease or poor cardiac output. Here, we describe a 78-year-old male with chronic
      obstructive pulmonary disease and congestive heart failure, whose incarcerated
      inguinal hernia self-reduced when he was given spinal anesthesia. Bowel viability
      was in question, so hernia sac laparoscopy without gas was performed, which
      allowed us adequate evaluation of the reduced bowel by positioning alone,
      avoiding both exploratory laparotomy and peritoneal insufflation. In our case,
      hernia sac laparoscopy under spinal anesthesia without pneumoperitoneum was
      sufficient to obtain necessary information with minimal surgical stress.

PMID- 17440794
TI  - Factors affecting morbidity and mortality in incarcerated abdominal wall hernias.
AB  - BACKGROUND: Incarcerated abdominal wall hernia cases may necessitate emergency
      interventions, but under such circumstances morbidity and mortality rates may
      increase. The aim of this study was to investigate the factors that affect
      morbidity and mortality in patients with incarcerated abdominal wall hernias who
      underwent emergency surgery. METHODS: Urgent surgical interventions due to
      incarcerated abdominal wall hernias were performed in 182 patients in our clinics
      between January 1998 and January 2006. Factors that affect morbidity and
      mortality in incarcerated abdominal wall hernias were investigated
      retrospectively by browsing the archives. Logistic regression analysis was used
      to evaluate parameters that affect morbidity and mortality. RESULTS: Morbidity
      and mortality occurred in 43 (23.6%) and 9 (4.9%) patients, respectively. A
      symptomatic period of longer than 8 h, presence of accompanying disease, high
      American Society of Anesthesiology (ASA) score, general anesthesia, presence of
      strangulation, and necrosis were found to affect morbidity significantly by
      univariate analysis. Necrosis was the sole factor affecting morbidity
      significantly by multivariate analysis. Advanced age, presence of accompanying
      disease, high ASA score, presence of strangulation, necrosis, and hernia repair
      with graft were found to affect mortality significantly by univariate analysis;
      however, necrosis was the sole factor affecting mortality significantly by
      multivariate analysis. CONCLUSIONS: Intestinal necrosis, which was followed by
      bowel resection, was the sole factor affecting morbidity and mortality using
      multivariate logistic regression analysis. Emergency surgery is required for
      incarcerated abdominal wall hernias before intestinal necrosis develops.

PMID- 17440796
TI  - Co-luminescence effect of heterometallic terbium-gadolinium hybrid molecular
      materials constructed by covalent grafting.
AB  - In this paper, 2-chlorobenzoic acid (CBA) and 2-chloronicotinic acid (CNA) were
      modified by 3-aminopropyl-trimethoxysilane (APMS) to afford corresponding organic
      inorganic monomers (CBA-APMS and CNA-APMS) with two components equipped with
      covalent bonds which not only can coordinate to RE ions (Tb(3+) and Gd(3+)) but
      also act as a sol-gel precursor. Luminescent hybrid materials consisting of
      terbium-gadolinium complex covalently bonded to silica-based network have been
      obtained in situ via a sol-gel approach. Through co-hydrolysis and
      polycondensation, Tb(3+) and Gd(3+) can be introduced in the same organic
      inorganic hybrid monomer and then formed Si-O backbones. The co-luminescence
      effect can be found by studying the luminescence spectra of different ratios of
      Tb(3+)-Gd(3+), which means that the existence of Gd(3+) can enhance the
      luminescence intensity, which may be due to the intramolecular energy transfer
      between Gd(3+) and Tb(3+).

PMID- 17440795
TI  - Discomfort five years after laparoscopic and Shouldice inguinal hernia repair: a
      randomised trial with 867 patients. A report from the SMIL study group.
AB  - BACKGROUND: In recent years long-term discomfort after inguinal hernia surgery
      has become an issue of great concern to hernia surgeons. Long-term results on
      discomfort from large randomised studies are sparse. METHODS: One-thousand one
      hundred and eighty-three patients were randomised in a multicentre trial with the
      primary aim of comparing recurrence rates after laparoscopic TAPP and Shouldice
      repair. Evaluating late discomfort and its possible risk factors were secondary
      objectives, and are reported here. The patients were clinically examined after 1
      and 5 years, and answered questionnaires 2 and 3 years postoperation. RESULTS: Of
      1,068 operated patients, 867 were eligible for analysis after 5 years (81.2%).
      The percentage of patients experiencing discomfort of any kind were 8.5% in the
      TAPP group and 11.4% (p = 0.156) in the Shouldice group. Although discomfort was
      usually mild it was severe for 0.2 and 0.7%, respectively. Severe pain the first
      postoperative week was a risk factor for late discomfort in the Shouldice group
      (OR 2.25, P = 0.022) but not in the TAPP group. No other risk factor for late
      discomfort was found. CONCLUSION: There was no difference between late discomfort
      at five-year follow-up after laparoscopic TAPP and Shouldice repair. Discomfort
      was mostly mild and pain during the first postoperative week was a prognostic
      variable for late discomfort in Shouldice patients.

PMID- 17440797
TI  - A new spectrofluorimetric method for determination of trace amounts 5
      hydroxytryptamine in human urine and serum.
AB  - A new spectrofluorimetric method was developed for the determination of trace
      amount of 5-hydroxytryptamine (5-HT) in human urine and serum samples. In the
      NaAc-HAc buffer solution of pH=5.80, 5-HT can react with formaldehyde
      acetylacetone system to form a new compound which sends yellow green fluorescence
      at 533 nm and the enhanced fluorescence intensity is in proportion to the
      concentration of 5-HT. Optimum conditions for the determination of 5-HT were also
      investigated. The dynamic range and detection limit for the determination of 5-HT
      are 5.35 x 10(-7) approximately 1.07 x 10(-4) mol/L and 2.08 x 10(-7) mol/L,
      respectively. The developed method is simple, practical and can be successfully
      applied to determination of 5-HT in human urine and serum samples. Moreover, the
      enhancement mechanisms of the fluorescence intensity in the 5-HT - formaldehyde
      acetylacetone system have been also discussed.

PMID- 17440798
TI  - Photophysical properties of novel ternary lanthanide complexes with long chain
      mono-L cis-butene dicarboxylate (L = hexadecyl, octadecyl and eicosyl) and 2,2'
      bipyridyl (or 1,10-phenanthroline).
AB  - Maleic anhydride was modified by long chain alcohol (1-hexadecanol, 1-octadecanol
      and 1-eicosanol) to a novel sort of corresponding long monoester mono-L cis
      butene dicarboxylate (L = hexadecyl, octadecyl and eicosyl), i.e. monohexadecyl
      cis-butene dicarboxylate (MAH), monooctadecyl cis-butene dicarboxylate (MAO), and
      monoeicosyl cis-butene dicarboxylate (MAE), respectively. Then the some novel
      ternary lanthanide (Eu3+, Tb3+) complexes with the as-derived long chain
      monoester and assistant nitrogen-heterocyclic ligands (2,2'-bipyridyl (bipy) and
      1,10-phenanthroline (phen)) were synthesized and characterized by elemental
      analysis and IR spectra. The photophysical properties of these complexes were
      studied in detail with ultraviolet absorption spectra, luminescent excitation and
      emission spectra and luminescent lifetimes, indicating that the intramolecular
      energy transfer mechanism runs smoothly within these ternary complexes in terms
      of sensitized functions of bipy and phen and strong characteristic red or green
      emissions of Eu3+ or Tb3+ have been achieved.

PMID- 17440799
TI  - Fluorimetric determination of some sulfur containing compounds through complex
      formation with terbium (Tb+3) and uranium (U+3).
AB  - Two simple, sensitive and specific fluorimetric methods have been developed for
      the determination of some sulphur containing compounds namely, Acetylcysteine
      (Ac), Carbocisteine (Cc) and Thioctic acid (Th) using terbium Tb+3 and uranium
      U+3 ions as fluorescent probes. The proposed methods involve the formation of a
      ternary complex with Tb+3 in presence of Tris-buffer method (I) and a binary
      complex with aqueous uranyl acetate solution method (II). The fluorescence
      quenching of Tb+3 at 510, 488 and 540 nm (lambda(ex) 250, 241 and 268 nm) and of
      uranyl acetate at 512 nm (lambda(ex) 240 nm) due to the complex formation was
      quantitatively measured for Ac, Cc and Th, respectively. The reaction conditions
      and the fluorescence spectral properties of the complexes have been investigated.
      Under the described conditions, the proposed methods were applicable over the
      concentration range (0.2-2.5 microg ml(-1)), (1-4 microg ml(-1)) and (0.5-3.5
      microg ml(-1)) with mean percentage recoveries 99.74+/-0.36, 99.70+/-0.52 and
      99.43+/-0.23 for method (I) and (0.5-6 microg ml(-1)), (0.5-5 microg ml(-1)), and
      (1-6 microg ml(-1)) with mean percentage recoveries 99.38+/-0.20, 99.82+/-0.28
      and 99.93+/-0.32 for method (II), for the three cited drugs, respectively. The
      proposed methods were successfully applied for the determination of the studied
      compounds in bulk powders and in pharmaceutical formulations, as well as in
      presence of their related substances. The results obtained were found to be in
      agree statistically with those obtained by official and reported ones. The two
      methods were validated according to USP guidelines and also assessed by applying
      the standard addition technique.

PMID- 17440800
TI  - Intrinsic bursting enhances the robustness of a neural network model of sequence
      generation by avian brain area HVC.
AB  - Avian brain area HVC is known to be important for the production of birdsong. In
      zebra finches, each RA-projecting neuron in HVC emits a single burst of spikes
      during a song motif. The population of neurons is activated in a precisely timed,
      stereotyped sequence. We propose a model of these burst sequences that relies on
      two hypotheses. First, we hypothesize that the sequential order of bursting is
      reflected in the excitatory synaptic connections between neurons. Second, we
      propose that the neurons are intrinsically bursting, so that burst duration is
      set by cellular properties. Our model generates burst sequences similar to those
      observed in HVC. If intrinsic bursting is removed from the model, burst sequences
      can also be produced. However, they require more fine-tuning of synaptic
      strengths, and are therefore less robust. In our model, intrinsic bursting is
      caused by dendritic calcium spikes, and strong spike frequency adaptation in the
      soma contributes to burst termination.

PMID- 17440802
TI  - Defining the behavioral phenotype of Asperger syndrome.
AB  - Asperger syndrome (AS) is characterized by social deficits and restricted
      interests in the absence of mental retardation and language delay. However, it is
      unclear to what extent the social deficits of AS differ from those of traditional
      autism. To address this issue, 58 subjects with AS were compared with 39 subjects
      with autism. Social deficits were classified according to Wing and Gould's
      method. Forty-six (79%) subjects with AS were rated as active but odd, while 32
      (82%) with autism were described as aloof and passive, while a few subjects
      showed mixed features. Thus, despite the overlap between AS and autism, subjects
      with AS showed a distinct pattern of social impairment. Implications of these
      findings are discussed.

PMID- 17440801
TI  - Capturing the bursting dynamics of a two-cell inhibitory network using a one
      dimensional map.
AB  - Out-of-phase bursting is a functionally important behavior displayed by central
      pattern generators and other neural circuits. Understanding this complex activity
      requires the knowledge of the interplay between the intrinsic cell properties and
      the properties of synaptic coupling between the cells. Here we describe a simple
      method that allows us to investigate the existence and stability of anti-phase
      bursting solutions in a network of two spiking neurons, each possessing a T-type
      calcium current and coupled by reciprocal inhibition. We derive a one-dimensional
      map which fully characterizes the genesis and regulation of anti-phase bursting
      arising from the interaction of the T-current properties with the properties of
      synaptic inhibition. This map is the burst length return map formed as the
      composition of two distinct one-dimensional maps that are each regulated by a
      different set of model parameters. Although each map is constructed using the
      properties of a single isolated model neuron, the composition of the two maps
      accurately captures the behavior of the full network. We analyze the parameter
      sensitivity of these maps to determine the influence of both the intrinsic cell
      properties and the synaptic properties on the burst length, and to find the
      conditions under which multistability of several bursting solutions is achieved.
      Although the derivation of the map relies on a number of simplifying assumptions,
      we discuss how the principle features of this dimensional reduction method could
      be extended to more realistic model networks.

PMID- 17440803
TI  - Subjective organisation in the free recall learning of adults with Asperger's
      syndrome.
AB  - Single trial methods reveal unimpaired free recall of unrelated words in
      Asperger's syndrome (AS). When repeated trials are used (free recall learning),
      typical individuals show improved recall over trials, subjective organisation of
      material (SO) and a correlation between free recall and SO. We tested oral
      (Experiment 1) and written (Experiment 2) free recall over 16 trials in adults
      with AS and typical individuals. Across both experiments AS participants showed
      marginally diminished recall. Poorer SO was seen in the Asperger group only in
      Experiment 2, but in both experiments, individual differences in SO in the
      Asperger group were less likely to converge over trials. This lack of convergence
      suggests that the AS group organise material in idiosyncratic ways.

PMID- 17440804
TI  - Transmembrane protein polymorphisms and resistance to T-20 (Enfuvirtide, Fuzeon)
      in HIV-1 infected therapy-naive seroconverters and AIDS patients under HAART-T-20
      therapy.
AB  - The human immunodeficiency virus type 1 fusion inhibitor T-20 (Enfuvirtide,
      Fuzeon) has recently been introduced into clinical practice. T-20 in combination
      with HAART efficiently inhibits HIV-1 replication, however T-20 resistance has
      been reported and the number of confirmed resistant-associated mutations is
      growing. In this study we aimed to analyze HIV-1 gp41 transmembrane protein (TM)
      variability and primary resistance to T-20 in plasma viruses from 10 HIV-1
      subtype B infected homosexuals. Nine out of ten were documented seroconverters.
      Nine individuals (including one long time infected therapy naive individual) were
      part of four linked virus infection chains. We also examined TM polymorphism in
      two AIDS patients under HAART and T-20 therapy. Obtained TM amplicons were
      examined for minor variants by clonal analysis.Sequences polymorphism of the N
      terminal regions of the fusion domain (FD) and the heptad repeat 2 (HR2) domain
      were demonstrated in examined seroconverters. Analysis of the heptad repeat 1
      (HR1) domain revealed T-20 resistance in cloned sequences from 3/10 individuals.
      In two individuals these mutations were present as minor viral quasispecies.
      Transmission of the resistant virus to the sexual partner was traced in virus
      infection chain.Baseline TM amplicons (population sequence) and clones from two
      patients under HAART did not contain T-20 resistance associated mutations. After
      onset of T-20 therapy only resistant viruses were identified in plasma from the
      patients. As shown by clonal analysis of plasma from one patient, treatment
      interruption results in viruses reverting to a T-20-sensitive genotype.

PMID- 17440805
TI  - Physical activity behavior change in middle-aged and older women: the role of
      barriers and of environmental characteristics.
AB  - The majority of North American women are insufficiently active. Using an
      ecological approach to examine physical activity behavior in a sample of middle
      aged and older women, this study aimed to (1) describe barriers to physical
      activity behavior change as well as environmental characteristics present in
      their neighborhoods, (2) examine relationships between barriers and physical
      activity behavior change, and (3) investigate environmental characteristics that
      may contribute to physical activity behavior change. Participants were 149 women
      ranging in age between 39 and 68. At Time 1, self-reported physical activity was
      assessed. Six months later (Time 2), barriers and environmental characteristics
      were measured, and physical activity was re-assessed. The most prevalent barriers
      were daily activities and fatigue. Over time, inactive women reported higher
      levels of barriers (e.g. fatigue, lack of interest in physical activity) than
      women who remained active or increased their physical activity level. Certain
      environmental characteristics (e.g. enjoyable scenery, seeing others exercising
      in their neighborhood) are suggested as potential contributors to physical
      activity behavior change.

PMID- 17440806
TI  - Predictors of success in implementing HIV prevention in rural America: a state
      level structural factor analysis of HIV prevention targeting men who have sex
      with men.
AB  - Relatively few studies have examined the impact of modifying structural factors
      on HIV prevention efforts in the United States despite their high potential for
      lowering HIV prevalence rates. The aim of this study was to identify state-level
      characteristics of successful HIV prevention implementation. Structured
      interviews with 73 key informants in 13 rural states identified 'more successful'
      and 'less successful' states in HIV prevention. States were compared on
      demographic, religious, gay community, and funding variables. The 7 more
      successful states had both a wider variety and more MSM-targeted interventions.
      Overall funding, degree of epidemic, and "ruralness" were not significantly
      associated with success. Rather, successful states had less religious and
      Evangelical Protestant adherents and more 'gay community' infrastructure. They
      also spent a greater proportion of funds contracting community-based
      organizations and on MSM-targeted programming. Success in HIV prevention varies
      across rural states. Key demographic, social and economic indicators distinguish
      success in HIV prevention.

PMID- 17440807
TI  - Molecular cloning, mapping, and tissue expression of the porcine cluster of
      differentiation 14 (CD14) gene.
AB  - CD14 plays an important role in initiating the innate response to
      lipopolysaccharide from Gram-negative bacteria. The gene and corresponding cDNA
      of porcine CD14 were sequenced and characterized. The porcine CD14 gene consists
      of two exons and a short intron (80 bp) located immediately after the ATG
      translation start codon. This structure is very similar to the CD14 gene of
      human, rat, mouse, rabbit, horse, and cow. The sequence of the porcine CD14
      protein is 59-76% identical to that of rat, mouse, rabbit, human, horse, and cow
      CD14 protein. A highly conserved structure of the CD14 protein with respect to
      the leucine-rich repeats domain and the N-glycosylation sites was observed
      between species. Porcine CD14 was assigned to porcine chromosome 2q21 by a
      radiation hybrid panel. Using RT-PCR analysis, porcine CD14 transcripts were
      detected in liver, spleen, thymus, white matter, and skeletal muscle.

PMID- 17440809
TI  - Algorithm for therapeutic management of acute heart failure syndromes.
AB  - As for other critically ill diseases, two key factors may markedly improved
      morbidity and mortality of acute heart failure syndromes (AHFS): early initiation
      of treatment and tailored therapy. Early initiation aims to stop the negative
      cascade of heart dysfunction. Tailored therapy should be based on the level of
      systolic blood pressure at admission and fluid retention. Indeed, EFICA and
      OPTIMIZE-HF showed that patients with high systolic blood pressure have a left
      ventricular systolic function that is likely preserved and those with low
      systolic blood pressure have a lower left ventricular ejection fraction and
      frequent signs of organ's hypoperfusion. Among the proposed treatments, non
      invasive ventilation is the only treatment that was consistently proven to be
      beneficial on morbidity and mortality in almost all types of AHFS. Concerning
      pharmacological agents, actions should be taken to increase the use of
      vasodilators and reduce the use of diuretics.

PMID- 17440808
TI  - Natriuretic peptides and therapeutic applications.
AB  - Since the discovery of atrial natriuretic factor by de Bold et al., there has
      been tremendous progress in our understanding of the physiologic, diagnostic and
      therapeutic roles of the natriuretic peptides (NPs) in health and disease.
      Natriuretic peptides are endogenous hormones that are released by the heart in
      response to myocardial stretch and overload. Three mammalian NPs have been
      identified and characterized, including atrial natriuretic peptide (ANP or atrial
      natriuretic factor), B-type natriuretic peptide (BNP), and C-type natriuretic
      peptide (CNP). In addition, Dendroaspis natriuretic peptide (DNP) has been
      isolated from the venom of Dendroaspis angusticeps (the green mamba snake), and
      urodilatin from human urine. These peptides are structurally similar and they
      consist of a 17-amino-acid core ring and a cysteine bridge. Both ANP and BNP bind
      to natriuretic peptide receptor A (NPR-A) that are expressed in the heart and
      other organs. Activation of NPR-A generates an increase in cyclic guanosine
      monophosphate, which mediates natriuresis, inhibition of renin and aldosterone,
      as well as vasorelaxant, anti-fibrotic, anti-hypertrophic, and lusitropic
      effects. The NP system thus serves as an important compensatory mechanism against
      neurohumoral activation in heart failure. This provides a strong rationale for
      the use of exogenous NPs in the management of acutely decompensated heart
      failure. In this article, the therapeutic applications of NPs in the acute heart
      failure syndromes are reviewed. Emerging therapeutic agents and areas for future
      research are discussed.

PMID- 17440810
TI  - Hydrogen peroxide induces lysosomal protease alterations in PC12 cells.
AB  - Alterations in lysosomal proteases have been implicated in many neurodegenerative
      diseases. The current study demonstrates a concentration-dependent decrease in
      PC12 cell viability and transient changes in cystatin C (CYSC), cathepsin B
      (CATB), cathepsin D (CATD) and caspase-3 following exposure to H2O2. Furthermore,
      activation of CATD occurred following exposure to H2O2 and cysteine protease
      suppression, while inhibition of CATD with pepstatin A significantly improved
      cell viability. Additionally, significant PARP cleavage, suggestive of caspase-3
      like activity, was observed following H2O2 exposure, while inhibition of caspase
      3 significantly increased cell viability compared to H2O2 administration alone.
      Collectively, our data suggest that H2O2 induced cell death is regulated at least
      in part by caspase-3 and CATD. Furthermore, cysteine protease suppression
      increases CATD expression and activity. These studies provide insight for
      alternate pathways and potential therapeutic targets of cell death associated
      with oxidative stress and lysosomal protease alterations.

PMID- 17440811
TI  - Systemic neurochemical alterations in schizophrenic brain: glutamate metabolism
      in focus.
AB  - We have used a systemic approach to establish a relationship between enzyme
      measures of glial glutamate and energy metabolism (glutamine synthetase and
      glutamine synthetase-like protein, glutamate dehydrogenase isoenzymes, brain
      isoform creatine phosphokinase) and two major glial proteins (glial fibrillary
      acidic protein and myelin basic protein) in autopsied brain samples taken from
      patients with schizophrenia (SCH) and mentally healthy subjects (23 and 22 cases,
      respectively). These biochemical parameters were measured in tissue extracts in
      three brain areas (prefrontal cortex, caudate nucleus, and cerebellum).
      Significant differences in the level of at least one of the glutamate
      metabolizing enzymes were observed between two studied groups in all studied
      brain areas. Different patterns of correlative links between the biochemical
      parameters were found in healthy and schizophrenic brains. These findings give a
      new perspective to our understanding of the impaired regulation of enzyme levels
      in the brain in SCH.

PMID- 17440813
TI  - Estimation of likely cancer cure using first- and second-order product densities
      of population balance models.
AB  - The objective of chemotherapy is to eradicate all cancerous cells. However, due
      to the stochastic behavior of cells, the elimination of all cancerous cells must
      be discussed probabilistically. We hypothesize, and demonstrate in the results,
      that the mean and standard deviation of a cancer cell population, derived through
      the probabilistic interpretation of population balance equations, are sufficient
      to estimate the likelihood of cancer eradication. Our analysis of a binary cell
      division model reveals that an expected cancer population that is six standard
      deviations less than one cell provides a good estimate for the treatment
      durations that nearly ensures treatment successes. This approximation is
      evaluated and tested on two other physiologically likely scenarios: variable
      patient response to chemotherapy and the presence of a dormant population. We
      find that early identification of individual patient susceptibility to the
      chemotherapeutic agent is extremely important to all patients as treatment
      adjustments for non-responders greatly enhances their likelihood of cure while
      responders need not be subjected to needlessly harsh treatments. Presence of a
      dormant population increases both the required treatment duration and population
      variability, but the same estimation method holds. This work is a step toward
      using stochastic models for a quantitative evaluation of chemotherapy.

PMID- 17440812
TI  - LRRK2 low-penetrance mutations (Gly2019Ser) and risk alleles (Gly2385Arg)-linking
      familial and sporadic Parkinson's disease.
AB  - The identification of mutations in the leucine-rich repeat kinase 2 (LRRK2) gene
      as a cause of autosomal dominant Parkinson's disease (PD) was a major step
      forward in the genetic dissection of this disorder. However, what makes LRRK2
      unique among the known PD-causing genes is that a low-penetrance mutation,
      Gly2019Ser, is a frequent determinant not only of familial, but also of sporadic
      PD in several populations from South Europe, North Africa and Middle East.
      Moreover, a different polymorphic variant, Gly2385Arg, is a frequent risk factor
      for PD among Chinese and Japanese populations. Currently, the Gly2019Ser and
      Gly2385Arg variants represent the most relevant PD-causing mutation and risk
      allele, respectively, linking the etiology of the familial and the sporadic forms
      of this disease. Understanding how the dysfunction of LRRK2 protein leads to
      neurodegeneration might provide crucial insights for unraveling the molecular
      mechanisms of PD and for developing disease-modifying therapies.

PMID- 17440814
TI  - Tissue transglutaminase induces the release of apoptosis inducing factor and
      results in apoptotic death of pancreatic cancer cells.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant disease with
      poor long-term survival rates. Major reason for poor disease outcome is the
      profound intrinsic resistance of PDAC cells to currently available treatment
      regimens. We recently found that a great majority of PDAC tumors and tumor cell
      lines express high basal level of tissue transglutaminase (TG2), a
      multifunctional protein implicated in apoptosis, cell attachment, cell survival,
      and cell motility functions. Based on these observations, we hypothesized that
      activation of endogenous TG2 can induce spontaneous apoptosis in PDAC cells. The
      results obtained suggested that activation of endogenous TG2 by calcium ionophore
      A23187 induced rapid and spontaneous apoptosis in PDAC cells. TG2-induced
      apoptosis was associated with release of apoptosis-inducing factor (AIF). The
      release of AIF from mitochondria led to its translocation to the nucleus and
      subsequent apoptosis of PDAC cells in caspase-independent manner. In conclusion,
      our results provide first evidence that TG2 can induce apoptosis in PDAC cells in
      an AIF-dependent and caspase-independent manner.

PMID- 17440816
TI  - Expression of anti-apoptotic factors modulates Apo2L/TRAIL resistance in colon
      carcinoma cells.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) selectively
      induces apoptosis in transformed cells. Normal cells and certain tumor cells can
      evade Apo2L/TRAIL induced cell death, but the determinants of Apo2L/TRAIL
      sensitivity are poorly understood. To better understand the factors that
      contribute to Apo2L/TRAIL resistance, we characterized two colon carcinoma lines
      with pronounced differences in Apo2L/TRAIL sensitivity. Colo205 cells are highly
      sensitive to Apo2L/TRAIL whereas Colo320 cells are unresponsive. Components of
      the DISC (death inducing signaling complex) could be immunoprecipitated from both
      cell lines in response to Apo2L/TRAIL. Sensitizing agents including a proteasome
      inhibitor conferred Apo2L/TRAIL sensitivity in Colo320 cells, indicating that the
      apoptotic machinery was intact and functional. We specifically suppressed the
      expression of Bcl-2, FLIP or XIAP in Colo320 cells. Downregulation of either FLIP
      or XIAP but not Bcl-2 restored sensitivity of Colo320 cells to Apo2L/TRAIL.
      Moreover, stable knockdown of XIAP expression in Colo320 subcutaneous tumors
      resulted in suppression of tumor growth and sensitivity to Apo2L/TRAIL in vivo.
      Our results indicate that only a specific subset of anti-apoptotic proteins can
      confer resistance to Apo2L/TRAIL in Colo320 cells. Elucidation of the factors
      that contribute to Apo2L/TRAIL resistance in tumor cells may provide insight into
      combination therapies with Apo2L/TRAIL in a clinical setting.

PMID- 17440815
TI  - Homocysteine affects cardiomyocyte viability: concentration-dependent effects on
      reversible flip-flop, apoptosis and necrosis.
AB  - BACKGROUND: Hyperhomocysteinaemia (HHC) is thought to be a risk factor for
      cardiovascular disease including heart failure. While numerous studies have
      analyzed the role of homocysteine (Hcy) in the vasculature, only a few studies
      investigated the role of Hcy in the heart. Therefore we have analyzed the effects
      of Hcy on isolated cardiomyocytes. METHODS: H9c2 cells (rat cardiomyoblast cells)
      and adult rat cardiomyocytes were incubated with Hcy and were analyzed for cell
      viability. Furthermore, we determined the effects of Hcy on intracellular
      mediators related to cell viability in cardiomyocytes, namely NOX2, reactive
      oxygen species (ROS), mitochondrial membrane potential (DeltaPsi (m)) and ATP
      concentrations. RESULTS: We found that incubation of H9c2 cells with 0.1 mM D,L
      Hcy (= 60 microM L-Hcy) resulted in an increase of DeltaPsi (m) as well as ATP
      concentrations. 1.1 mM D,L-Hcy (= 460 microM L-Hcy) induced reversible flip-flop
      of the plasma membrane phospholipids, but not apoptosis. Incubation with 2.73 mM
      D,L-Hcy (= 1.18 mM L-Hcy) induced apoptosis and necrosis. This loss of cell
      viability was accompanied by a thread-to-grain transition of the mitochondrial
      reticulum, ATP depletion and nuclear NOX2 expression coinciding with ROS
      production as evident from the presence of nitrotyrosin residues. Notably, only
      at this concentration we found a significant increase in S-adenosylhomocysteine
      which is considered the primary culprit in HHC. CONCLUSION: We found
      concentration-dependent effects of Hcy in cardiomyocytes, varying from induction
      of reversible flip-flop of the plasma membrane phospholipids, to apoptosis and
      necrosis.

PMID- 17440817
TI  - Molecular mechanisms of euplotin C-induced apoptosis: involvement of
      mitochondrial dysfunction, oxidative stress and proteases.
AB  - The metabolite euplotin C (EC), isolated from the marine ciliate Euplotes
      crassus, is a powerful cytotoxic and pro-apoptotic agent in tumour cell lines.
      For instance, EC induces the rapid depletion of ryanodine Ca(2+) stores, the
      release of cytochrome c from the mitochondria, and the activation of caspase-3,
      leading to apoptosis. The purpose of this study was to gain further insight into
      the mechanisms of EC-induced apoptosis in rat pheochromocytoma PC12 cells. We
      found that EC increases Bax/Bcl-2 ratio and that Bax is responsible of the EC
      induced dissipation of the mitochondrial membrane potential (Deltapsi(m)). In
      addition, EC induces the generation of reactive oxygene species (ROS) without
      involvement of p53. The inhibition of ROS generation prevents, at least in part,
      the pro-apoptotic effects of EC as well as the effects of EC on Bax, Deltapsi(m)
      and intracellular free Ca(2+), indicating a cross-talk between different
      pathways. However, definition of the effector cascade turns out to be more
      complex than expected and caspase-independent mechanisms, acting in parallel with
      caspases, should also be considered. Among them, EC increases the
      expression/activity of calpains downstream of ROS generation, although calpains
      seem to exert protective effects.

PMID- 17440818
TI  - Smac/DIABLO is required for effector caspase activation during apoptosis in human
      cells.
AB  - Mitochondria play a pivotal role during stress-induced apoptosis as several
      proapoptotic proteins are released to the cytosol to activate caspases.
      Smac/DIABLO is one of the proapoptotic proteins released from the mitochondria
      and has been shown to inactivate IAPs. However, gene knockout studies in mice
      revealed a redundant role for Smac during development and cell death. By applying
      RNA interference-mediated loss of function approach, we demonstrate that
      Smac/DIABLO is required for the activation of effector but not initiator caspases
      during stress and receptor-mediated cell death in HeLa cells. Cells with reduced
      Smac resist apoptosis and retained clonogenicity. Our results suggest an
      obligatory role for Smac/DIABLO in these tumor cells during several pathways of
      apoptosis induction.

PMID- 17440819
TI  - SERMs for the treatment and prevention of breast cancer.
AB  - Tamoxifen and raloxifene are both selective estrogen receptor modulators (SERMs).
      The medicines can block estrogen mediated breast cancer growth and development
      but will also maintain bone density in postmenopausal women and lower circulating
      cholesterol. Tamoxifen has remained the antihormonal therapy of choice for the
      treatment of ER positive breast cancer for the last 30 years. However, although
      adjuvant tamoxifen produces profound increases in disease-free and overall
      survival in patients with ER positive breast cancer, concerns about drug
      resistance, blood clots and endometrial cancer have resulted in a change to the
      use of aromatase inhibitors for the treatment of postmenopausal women.
      Nevertheless, tamoxifen remains the antihormonal treatment of choice for
      premenopausal women with ER positive breast cancer and for risk reduction in
      premenopausal women who are at high risk for developing breast cancer. The risk
      of endometrial cancer and thromboembolic disorders during tamoxifen therapy is
      not elevated in premenopausal women. It is important to note that aromatase
      inhibitors or raloxifene should not be used in premenopausal women. Raloxifene is
      used to prevent osteoporosis in postmenopausal women and, unlike tamoxifen, does
      not increase the risk of endometrial cancer. However, raloxifene does reduce
      breast cancer risk by 50-70% in both low risk and high risk postmenopausal women.
      Comparisons of raloxifene with tamoxifen show equal efficacy as a chemopreventive
      for breast cancer but there is a reduction in thromboembolic disorders, fewer
      endometrial cancers, hysterectomies, cataracts and cataract surgeries in women
      taking raloxifene. Overall, SERMs continue to fulfill their promise as
      appropriate medicines that target specific populations for the treatment and
      prevention of breast cancer.

PMID- 17440820
TI  - An unusual association of a sellar gangliocytoma with a prolactinoma.
AB  - The simultaneous occurrence of a hypothalamic and sellar gangliocytoma with a
      pituitary prolactinoma is very rare. The explanation for such an association is
      not known. We describe the case of a woman who had a coexisting adjacent
      pituitary prolactinoma and gangliocytoma within the same sellar mass. The tumor
      cells of the gangliocytoma demonstrated expression of enkephalin, a product of
      proopiomelanocortin known to be a prolactin secretagogue. We postulate that in
      this patient there may be a link between gangliocytoma enkephalin and prolactin
      hypersecretion.

PMID- 17440821
TI  - Tomato linalool synthase is induced in trichomes by jasmonic acid.
AB  - Tomato (Lycopersicon esculentum) plants emit a blend of volatile organic
      compounds, which mainly consists of terpenes. Upon herbivory or wounding, the
      emission of several terpenes increases. We have identified and characterized the
      first two tomato monoterpene synthases, LeMTS1 and LeMTS2. Although these
      proteins were highly homologous, recombinant LeMTS1 protein produced (R)-linalool
      from geranyl diphosphate (GPP) and (E)-nerolidol from farnesyl diphosphate (FPP),
      while recombinant LeMTS2 produced beta-phellandrene, beta-myrcene, and sabinene
      from GPP. In addition, these genes were expressed in different tissues: LeMTS1
      was expressed in flowers, young leaves, stems, and petioles, while LeMTS2 was
      strongest expressed in stems and roots. LeMTS1 expression in leaves was induced
      by spider mite-infestation, wounding and jasmonic acid (JA)-treatment, while
      LeMTS2 did not respond to these stimuli. The expression of LeMTS1 in stems and
      petioles was predominantly detected in trichomes and could be induced by JA.
      Because JA treatment strongly induced emission of linalool and overexpression of
      LeMTS1 in tomato resulted in increased production of linalool, we propose that
      LeMTS1 is a genuine linalool synthase. Our results underline the importance of
      trichomes in JA-induced terpene emission in tomato.

PMID- 17440822
TI  - A novel study investigating the therapeutic outcome of patients with lytic, mixed
      and sclerotic bone metastases treated with combined radiotherapy and ibandronate.
AB  - PURPOSE: To investigate the therapeutic response of patients with different types
      of bone metastases treated with combined radiotherapy and bisphosphonates.
      PATIENTS AND METHODS: By using computed tomography 52 patients were grouped into
      groups of lytic, mixed and sclerotic bone lesions. All patients were treated with
      concomitant radiotherapy and ibandronate (10 monthly cycles) and underwent
      clinical and radiological evaluations prior to therapy and at 3, 6 and 10 months
      of follow up. RESULTS: At baseline there were statistically significant
      differences between the three groups for all the evaluated parameters. From 3
      months onwards differences were leveled out. Statistically significant
      improvements were noted at all time points of evaluation for all groups in
      parameters such as pain (0-10), quality of life (QOL-physical functioning, 0-100)
      and Karnofsky performance status (KPS). The average pain score for the lytic
      group was reduced from 8.1 to 1.5 points at 3 months. The corresponding
      reductions for the mixed and sclerotic groups were from 6.2 to 0.5 and from 4.4
      to 0.3 points respectively. Complete pain responses were >76.4% at all time
      points for all groups. Opioid consumption was also markedly reduced. Overall, the
      highest clinical response was noted for the lytic group, even though the mean
      values of pain, QOL and KPS were worse than those of the two other groups at all
      time points (apart from pain score at 10 months). The percentage of patients of
      the lytic group experiencing a complete pain response was the least of the three
      groups during follow up. At 10 months bone density was almost tripled for the
      lytic and almost doubled for the mixed group. CONCLUSIONS: Even though the
      therapeutic outcome for the three groups was similar, the degree of clinical
      response and reossification differed.

PMID- 17440823
TI  - Glycoconjugate histochemistry of the digestive tract of Triturus carnifex
      (Amphibia, Caudata).
AB  - In this study, the variety of sugar residues in the gut glycoconjugates of
      Triturus carnifex (Amphibia, Caudata) are investigated by carbohydrate
      conventional histochemistry and lectin histochemistry. The oesophageal surface
      mucous cells contained acidic glycoconjugates, with residues of GalNAc, Gal
      beta1,3 GalNAc and (GlcNAc beta1,4)(n) oligomers. The gastric surface cells
      mainly produced neutral glycoproteins with residues of fucose, Gal beta1-3
      GalNAc, Gal-alphaGal, and (GlcNAc beta1,4)(n) oligomers in N- and O-linked
      glycans, as the glandular mucous neck cells, with residues of mannose/glucose,
      GalNAc, Gal beta1,3 GalNAc, (GlcNAc beta1,4)(n)oligomers and fucose linked
      alpha1,6 or terminal alpha1,3 or alpha1,4 in O-linked glycans. The oxynticopeptic
      tubulo-vesicular system contained neutral glycoproteins with N- and O-linked
      glycans with residues of Gal-alphaGal, Gal beta1-3 GalNAc and (GlcNAc
      beta1,4)(n)oligomers; Fuc linked alpha1,2 to Gal, alpha1,3 to GlcNAc in
      (poly)lactosamine chains and alpha1,6 to GlcNAc in N-linked glycans. Most of
      these glycoproteins probably corresponds to the H(+)K(+)-ATPase beta-subunit. The
      intestinal goblet cells contained acidic glycoconjugates, with residues of
      GalNAc, mannose/ glucose, (GlcNAc beta1,4)(n)oligomers and fucose linked alpha1,2
      to Gal in O-linked oligosaccharides. The different composition of the mucus in
      the digestive tracts may be correlated with its different functions. In fact the
      presence of abundant sulphation of glycoconjugates, mainly in the oesophagus and
      intestine, probably confers resistance to bacterial enzymatic degradation of the
      mucus barrier.

PMID- 17440824
TI  - Effect of beta-blockers on beta3-adrenoceptor expression in chronic heart
      failure.
AB  - OBJECTIVES: To investigate the expression of beta(3)-adrenoceptors in rats with
      chronic heart failure, and to explore the effect of beta-blockers on beta(3)
      adrenoceptor expression. MATERIALS AND METHODS: Thirty-two male Wistar rats were
      divided into Sham (n = 10) and heart failure (n = 22) groups. The heart failure
      group was treated with normal saline (Heart Failure Control, n = 6), Metoprolol
      (n = 8) or Carvedilol (n = 8) for 3 months. RESULTS: The left ventricular end
      systolic pressure (LVESP) and the absolute values of maximal rate of rise and
      fall of left ventricular pressure (+/-dP/dt max) in the heart failure group were
      lower than in the Sham group (P < 0.01), whereas the left ventricular end
      diastolic pressure (LVEDP) was higher (P < 0.01). The LVESP and dP/dtmax in the
      Carvedilol group were higher than the Metoprolol group whereas LVEDP was lower (P
      < 0.01). The left ventricular mass index (LVMI) in the Carvedilol group was less
      than the Metoprolol and Heart Failure Control groups (P < 0.01). The level of
      beta(3)-adrenoceptor expression in the study groups was significantly higher than
      the Sham group (P < 0.01). beta(3)-adrenoceptor expression in the Carvedilol
      group was lower than the Heart Failure Control and Metoprolol groups (P < 0.01).
      CONCLUSION: beta(3)-adrenoceptor expression is increased in the failing
      ventricles in rats. Carvedilol is more effective than Metoprolol for improving
      the hemodynamics and in attenuating ventricular remodeling after heart failure.
      Carvedilol, rather than Metoprolol, diminishes beta(3)-adrenoceptor expression in
      the failing ventricles.

PMID- 17440825
TI  - Scanning the horizon: what is the future of genome-wide association studies in
      accelerating discoveries in cancer etiology and prevention?
AB  - Genome-wide association studies using recently developed large scale single
      nucleotide polymorphism platforms are beginning to be performed, and results
      reported. Initial indications are that these studies are capable of discovering
      loci associated with relative risks too modest to have been detectable through
      family-based linkage studies. However, as these studies initially test 500,000 or
      more polymorphisms in a first series of cases and controls, the need for robust
      replication in one, or preferably, several independent studies is paramount to
      winnow out the true positive results from the large number of expected false
      positives. We discuss the need for the formation of consortia to conduct these
      multi-stage studies, and stress the importance of full disclosure of allele
      frequencies in cases and controls from these studies in order to facilitate joint
      analyses across datasets to speed discovery of reproducible associations, and to
      explore more complex associations such as gene-gene interactions. Desirable
      characteristics of studies in which genome-wide association studies will be most
      informative are discussed. The validation of genetic variants that alter risk of
      specific cancers may be relevant to screening, the identification of high risk
      persons for risk-reducing interventions, and the discovery of new biological
      mechanisms that may provide insight into cancer causes and preventive strategies.

PMID- 17440826
TI  - Prediction of mutagenic toxicity by combination of Recursive Partitioning and
      Support Vector Machines.
AB  - The study of prediction of toxicity is very important and necessary because
      measurement of toxicity is typically time-consuming and expensive. In this paper,
      Recursive Partitioning (RP) method was used to select descriptors. RP and Support
      Vector Machines (SVM) were used to construct structure-toxicity relationship
      models, RP model and SVM model, respectively. The performances of the two models
      are different. The prediction accuracies of the RP model are 80.2% for mutagenic
      compounds in MDL's toxicity database, 83.4% for compounds in CMC and 84.9% for
      agrochemicals in in-house database respectively. Those of SVM model are 81.4%,
      87.0% and 87.3% respectively.

PMID- 17440827
TI  - Life satisfaction decreases during adolescence.
AB  - OBJECTIVE: Adolescence is a developmental phase associated with significant
      somatic and psychosocial changes. So far there are few studies on developmental
      aspects of life satisfaction. This cross-sectional study examines the effects of
      age and gender on adolescent's life satisfaction. METHODS: 1,274 German
      adolescents (aged 11-16 years) participated in a school-based survey study. They
      completed the adolescent version of the Questions on Life Satisfaction (FLZ(M) -
      Fragen zur Lebenszufriedenheit), a multidimensional instrument measuring the
      subjective importance and satisfaction with eight domains of general and eight
      domains of health-related life satisfaction. Effects of gender and age were
      analysed using ANOVAs. RESULTS: Girls reported significantly lower general (F =
      5.0; p = .025) and health-related life satisfaction (F = 25.3; p < .001) compared
      to boys. In both genders and across nearly all life domains, there was a
      significant decrease in general (F = 14.8; p < .001) and health-related life
      satisfaction (F = 8.0; p < .001) between 11 and 16 years. Satisfaction with
      friends remained on a high level, whereas satisfaction with family relations
      decreased. Only satisfaction with partnership/sexuality increased slightly,
      however this effect cannot compensate the general loss of satisfaction.
      CONCLUSIONS: Decreasing life satisfaction has to be considered as a developmental
      phenomenon. Associations with the increasing prevalence of depression and
      suicidal ideation during adolescence are discussed. Life satisfaction should be
      considered a relevant aspect of adolescent's well-being and functioning.

PMID- 17440828
TI  - Measurement of overall quality of life in nursing homes through self-report: the
      role of cognitive impairment.
AB  - Measuring quality of life is a necessity for adequate interventions. This paper
      concerns the usefulness of six self-report measures for overall quality of life
      for nursing home residents with various levels of cognitive impairment. It was
      investigated which proportion of residents from four cognition groups could
      complete a scale, and internal consistency and construct validity of the scales
      were studied. Data collection took place in ten Dutch nursing homes (N = 227).
      The proportion of residents that could complete each scale varied. The Depression
      List could be administered most often to the cognitively most impaired group
      (43%; Mini Mental State Examination-scores 0-4). In the three cognition groups
      with MMSE-score >5, internal consistency of the Depression List, Geriatric
      Depression Scale and Negative Affect Scale was adequate in all three groups
      (alpha > or =.68). Intercorrelation was highest for the Philadelphia Geriatric
      Center Morale Scale, the Depression List, and the Geriatric Depression Scale (rho
      > or =.65). Nonetheless, self-report scales were not strongly correlated with two
      observational scales for depression, especially in cognitively severely impaired
      residents (rho < or =.30). In conclusion, it may not be possible to measure
      overall quality of life through self-report, and possibly also through
      observation, in many nursing home residents.

PMID- 17440829
TI  - Effect of trauma on quality of life as mediated by mental distress and moderated
      by coping and social support among postconflict displaced Ethiopians.
AB  - OBJECTIVE: An understanding of how quality of life is affected by severe trauma
      and mental distress may facilitate better intervention strategies for
      postconflict internally displaced persons, by identifying mediators, moderators,
      and independent risk factors. We investigate the pathways involved in this
      process and also study the moderating roles of coping strategies and perceived
      social support. METHOD: A random sample of 1193 (62% women) internally displaced
      Ethiopian adults living in shelters in Addis Ababa were interviewed with
      instruments capturing the relevant concepts, including SCL-90-R and WHOQOL-BREF.
      Path analysis was employed to elaborate the mediating and moderating effects.
      Self-reported living conditions were also assessed. RESULTS: Mental distress
      increased and quality of life decreased with age. Mental distress mediated the
      effects of trauma in reducing the quality of life, and some trauma also reduced
      quality of life directly. These effects remained after adjusting for living
      conditions. Living conditions were related to quality of life also on their own.
      Coping strategies and perceived social support influenced mental distress and
      quality of life directly as well as indirectly by moderation, in part gender
      specific. CONCLUSIONS: Intervention strategies aimed at reducing mental distress,
      modifying coping strategies, and encouraging social support may turn out to be
      useful in increasing the overall quality of life in postconflict situations, and
      are worth considering as complements to strategies that improve the living
      conditions.

PMID- 17440830
TI  - Cultural adaptation and application of the IBS-QOL in China: a disease-specific
      quality-of-life questionnaire.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a chronic and episodic illness
      characterized by altered bowel habits and associated abdominal pain. At present,
      IBS is one of the most common functional gastrointestinal and motility disorders
      affecting countries around the world. Surveys have found that patients with IBS
      have a significantly lower health-related quality of life. OBJECTIVES: The aim of
      this study was to translate and examine the validity of the Irritable Bowel
      Syndrome-Quality of Life questionnaire (IBS-QOL) in patients suffering from IBS
      in China. METHODS: A structured procedure was used for the translation and
      cultural adaptation of the original English IBS-QOL into Chinese. The
      questionnaire was administered to 73 clinical patients with IBS and 70 healthy
      individuals. Psychometric testing for reliability, validity and responsiveness
      followed standardized procedures. Test-retest reliability (10-20 hours) was
      assessed using the clinical patients. Follow-up (4 weeks) was collected for 61
      clinical patients. All enrolled patients also completed the Short Form-36 Health
      Survey (SF-36) at the baseline visit. Responsiveness to treatment (Venlafaxine
      and traditional Chinese herbal medicine) was assessed by one-way ANOVA methods.
      RESULTS: The average length of time required to complete the questionnaire was
      short (5.63 min for IBS patients and 5.54 min for healthy subjects by self
      administration). Internal consistency (Cronbach's alpha) values ranged from 0.722
      to 0.914 for the Chinese IBS-QOL subscales and test-retest reliability
      coefficients were higher than 0.920 on all subscales. The convergent and
      discriminate validity results comparing the Chinese translation of the IBS-QOL
      overall score and the SF-36 subscales confirmed our predicted hypotheses. The
      Chinese IBS-QOL scores are more highly correlated with social functioning,
      vitality and general health (SF-36) and show weaker associations with physical
      functioning, role physical, mental health, and bodily pain (SF-36). The Chinese
      translation of the IBS-QOL was responsive to treatment. CONCLUSION: In general,
      the Chinese translation of the IBS-QOL, after cultural adaptation and revision,
      possesses good reliability, validity and responsiveness. It is a reliable and
      valid instrument to assess the quality of life in Chinese patients suffering from
      IBS and is an appropriate measure to use in further clinical trials or for
      related research projects in China.

PMID- 17440831
TI  - Procedure control and acceptance sampling plans for donor sperm banks: a
      theoretical study.
AB  - The publication of European Directive 2004/23/EC in the European Parliament and
      in the European Council on 31 March 2004 concerning the setting of standards of
      quality and safety for the donation, procurement, testing, processing,
      preservation, storage and distribution of human cells and tissues made it
      obligatory for sperm banks to set up quality control systems to ensure, among
      other goals, the satisfactory control of all procedures carried out. The
      objective of the present study is to set out guidelines that will make it
      possible to ensure the quality of the donors and frozen specimens accepted and
      the homogeneity of the samples supplied by a sperm bank. For this purpose, we
      shall describe clear-cut criteria for the acceptance of donors and frozen sperm,
      taking into account both analytic variability and the biological variations to be
      expected in semen parameters. Furthermore, we shall show how the evaluation of
      the results of a frozen semen specimen, on the basis of analysing a single straw
      after such freezing, does not guarantee the homogeneity of all the straws.
      Therefore, we must design a sampling plan to take into consideration all the
      straws obtained from a donor. This kind of plan will depend on different
      parameters, such as acceptable levels of quality and the tolerable rate of straws
      with defective semen, and will involve certain risks, both for the sperm bank and
      for the client. The establishment of these acceptance control criteria for frozen
      specimens and for donors could be of practical use for the control of the
      procedures applied in the operation of a sperm bank.

PMID- 17440832
TI  - Decontamination of heart valve and arterial allografts in the European Homograft
      Bank (EHB): comparison of two different antibiotic cocktails in low temperature
      conditions.
AB  - The aim of the study was to compare the efficiency of two different antibiotic
      cocktails in the cardiovascular allograft decontamination. Low temperature, low
      concentration antibiotic cocktail with Cefoxitin, Lincomycin, Polymixin B and
      Vancomycin was decontamination protocol in EHB for many years. The modified
      cocktail doesn't contain Cefoxitin. The study had two steps. First step:
      cardiovascular allografts from 80 donors are incubated in classical (group 1) or
      modified cocktail (group 2). Second step: 184 and 182 allografts of group 1 and
      group 2 are incubated in the modified and classical antibiotic cocktail,
      respectively. The bacteriological examination is performed in three steps: A
      transport solution, B-decontamination solution and C-cryopreservation solution.
      During the first step 23.75% of the tissues were initially contaminated mainly
      with Staphylococcus (78.95%). 93.75% of the allografts of group 1 and 100% of
      group 2 were sterile after incubation (p = 0.058). 25.54% and 30.77% of group 1
      and 2, respectively were contaminated in A-examination during the second step.
      Staphylococci were isolated in 82.98% and 69.64% in group 1 and 2, respectively.
      About 4.35% of group 1 and 5.5% of group 2 were contaminated in A, B, and C
      whereas 5.4% of group 1 and 4.4% of group 2 were contaminated in B or C after
      being sterile in A. Finally 9.78% of the tissues were rejected and 90.22%
      cryopreserved in the modified, whereas 9.89% rejected and 90.11% accepted in the
      classical group (p = 0.1). The difference was non-significant in the level of
      decontamination between the two cocktails. Contamination of some tissues with low
      growing, low-pathogen germs that appeared in B or C examination, couldn't be
      explained. This issue needs complementary investigation.

PMID- 17440833
TI  - Investigating the warming and cooling rates of human cadavers by development of a
      gel-filled model to validate core temperature.
AB  - Tissue Services (within NHS Blood and Transplant) plans to bring deceased donors
      to its state of the art retrieval suite at its new centre in Speke, Liverpool in
      air-conditioned transport at circa 20 degrees C but without dedicated active
      cooling. The aim of this study was to determine how quickly a refrigerated body
      would warm at different ambient temperatures using a gel-filled model. Two models
      of a human body were prepared consisting of neoprene wetsuits filled with
      approximately 7 or 18 l of a viscous solution, which once set has similar
      properties to ballistics gel. This gel consisted of 47.5% distilled water, 47.5%
      glycerol and 5% agar. Final "dummy" weights were 7.4 and 18.6 kg respectively,
      representing "virtual" weights of approximately 40 kg and 70 kg. A K-class
      thermocouple probe was then inserted into a "rectal" position within each model
      and the models were cooled to a series of different core temperatures: 5 degrees
      C, 10 degrees C and 15 degrees C and then were placed in an orbital incubator set
      at 20 degrees C or 30 degrees C ambient temperature. The rate of temperature
      increase, in the dummy, was measured, until the model's core temperature was
      close to the ambient temperature. This was done in triplicate for each size model
      and ambient temperature. Data indicate that increase in core temperature depends
      on the size of the model and the initial core temperature. For an equivalent
      donor weight of 70 kg and background temperature of 20 degrees C, core
      temperature rises from 5 degrees C to 9.2 degrees C; 10 degrees C to 13.3 degrees
      C and 15 degrees C to 15.5 degrees C after 2 h. The final core temperatures after
      2 h are likely to retard bacterial growth, movement or contamination during
      transport. Cooling rate data indicated that a 70 kg donor equivalent cooled from
      37 degrees C to 15 degrees C within 6 h in a cold room at 4 degrees C. This work
      has shown that a body can be transported without refrigeration and not cause
      further tissue deterioration as a result.

PMID- 17440834
TI  - Donor derived malignancy following transplantation: a review.
AB  - Organ and tissue transplant is now the treatment of choice for many end stage
      diseases. In the recent years, there has been an increasing demand for organs but
      not a similar increase in the supply leading to a severe shortage of organs for
      transplant resulted in increasing wait times for recipients. This has resulted in
      expanded donor criteria to include older donors and donors with mild disease. In
      spite of implementation of more stringent criteria for donor selection, there
      continues to be some risk of donor derived malignancy. Malignancy after
      transplantation can occur in three different ways: (a) de-novo occurrence, (b)
      recurrence of malignancy, and (c) donor-related malignancy. Donor related
      malignancy can be either due to direct transmission of tumor or due to tumor
      arising in cells of donor origin. We will review donor related malignancies
      following solid organ transplantation and hematopoeitic progenitor cell
      transplantation. Further, we will briefly review the methods for detection and
      management of these donor related malignancies.

PMID- 17440835
TI  - Reduced survivin expression and tumor cell survival during chronic hypoxia and
      further cytotoxic enhancement by the cyclooxygenase-2 inhibitor celecoxib.
AB  - Hypoxia is a characteristic feature of advanced solid tumors and may worsen
      prognosis. The development of tumor-targeted and hypoxia-inducible gene therapy
      vectors holds promise to selectively deliver and express suicidal or cytotoxic
      genes in hypoxic regions of tumors. In this regard, the promoter of the survivin
      gene, which encodes an anti-apoptotic protein that is strongly expressed in tumor
      tissue, has received attention because of its supposed inducibility by hypoxia.
      However, in our present study we demonstrate that treatment of various tumor cell
      lines with chronic hypoxia or with the hypoxia-mimetic CoCl(2) does not result in
      increased expression of survivin, but rather strongly suppresses this gene's
      activity. In contrast, expression of glucose-regulated protein 78 (GRP78/Bip) is
      substantially elevated under chronic hypoxia in vitro and in hypoxic areas of
      tumor tissue in vivo. Although tumor cells in general exhibit increased
      chemoresistance under hypoxic conditions, we found that hypoxic glioblastoma
      cells are more sensitive to killing by the selective cyclooxygenase-2 (COX-2)
      inhibitor celecoxib, and this effect is reflected by further decreased expression
      of survivin. Intriguingly, 2,5-dimethyl-celecoxib (DMC), a close structural
      analog of celecoxib that lacks the ability to inhibit COX-2, is able to potently
      mimic the anti-tumor effects of its parent compound, indicating that inhibition
      of COX-2 is not involved in these processes. Taken together, our results caution
      against the use of survivin-based promoters to target hypoxic areas of tumors,
      but favor constructs that include the strongly hypoxia-inducible GRP78 promoter.
      In addition, our data introduce celecoxib as a drug with increased cytotoxicity
      against hypoxic tumor cells.

PMID- 17440837
TI  - [Social medicine: quality, humanity and economic efficiency].

PMID- 17440836
TI  - Internal representations of smell in the Drosophila brain.
AB  - Recent advances in sensory neuroscience using Drosophila olfaction as a model
      system have revealed brain maps representing the external world. Once we
      understand how the brain's built-in capability generates the internal olfactory
      maps, we can then elaborate how the brain computes and makes decision to elicit
      complex behaviors. Here, we review current progress in mapping Drosophila
      olfactory circuits and discuss their relationships with innate olfactory
      behaviors.

PMID- 17440838
TI  - [Lecture on the occasion of the award of the Salomon-Neumann Medal to the
      "Gemeinsame Bundesausschuss" (G-BA)].

PMID- 17440839
TI  - [Social capital and health in Germany].
AB  - The concept of social capital has been intensively discussed in public health
      during the last years. But there is only little empirical evidence regarding its
      association with health in Germany up to now. We have used data of the German
      Socio-Economic Panel (GSOEP) of 2003 to analyse the health utility of social
      capital. The results suggest a clear positive association among different forms
      of social capital (trust, norms of reciprocity, participation, social
      integration) and subjective health. Men and women who are poorly socially
      integrated regard their own health relatively often as limited. In contrast to
      these, men and women who hold any form of social capital rate their own health
      status to be noticeably better. In the multivariate analysis, socio-economic
      differences in subjective health could be traced back partly to the stock of
      social capital. In addition to its health utility, social capital may therefore
      make a contribution to understand the emergence of social inequalities in health.
      All in all, our results suggest that the concept of social capital should be
      considered even more in public health. Due to the present lack of empirical
      evidence, social capital has to be incorporated into more studies in Germany.

PMID- 17440840
TI  - [Perspectives in long-term care insurance].
AB  - Twelve years after its introduction, long-term care insurance is back on the
      agenda and up for political reform. This paper shows why long-term care insurance
      needs to be reformed. The two central aspects on which reform projects focus are
      addressed: firstly, the structural improvement of nursing care and long-term care
      insurance and, secondly, the creation of a sustained financing. The principal
      conclusion is that, while there is a broad consensus about the structural
      improvement of long-term care insurance, opinions differ widely in the matter of
      its sustained financing. As a consequence, a coherent financing concept has yet
      to emerge.

PMID- 17440841
TI  - [Social-medical significance of the concept of salutogenesis in neurology and
      psychiatry].
AB  - The so-called "sense of coherence" (SOC) is the central idea of Antonovsky's
      concept of salutogenesis. The structure and the meaning of SOC for a person's
      ability to cope with stress are discussed as well as the overall health-promoting
      effect of SOC. At the end of the study's first part the question of proving the
      SOC empirically and of the SOC's construct validity are critically discussed. The
      second part of the article demonstrates the relevance of salutogenic mechanisms
      for psychiatry and neurology, especially regarding the social aspects of both
      disciplines. Health promotion and disease prevention are already important issues
      in the Mental Health Community. But also in neurology, which is much more
      grounded in the physical medicine than psychiatry, the concept of salutogenesis
      can help patients to prevent illness or to cope better with the consequences of
      diseases. Finally, the necessity to supply the current health care system in
      psychiatry and neurology with much more salutogenic input is questioned.

PMID- 17440842
TI  - [Random sampling according to section 17 c KHG--report on the experience of
      maximal care hospitals in Hesse].
AB  - Hospital billing converted to "German diagnosis-related groups" (G-DRG) for in
      patient treatment in Germany is reviewed, except in psychiatry where per-diems
      are still in use. Currently thousands of bills are sent to the Medical Service
      for scrutiny. In addition, the law relating to Hospital Financing
      (Krankenhausfinanzierungsgesetz, para. 17 c) provides for systematic checks on a
      random sample of bills from a given hospital. The Medical Service of the Social
      Security Health Insurance reports on the experience in the State of Hessen.
      Present regulations exclude from the random sample those bills that have already
      been presented for a check on a case by case basis. Excluding these cases from
      the random sample introduces a bias in an avoidable way. The present rule is
      contrary to valid conclusions from the random sampling and should be abolished.

PMID- 17440843
TI  - [DRG evaluation results--state comparisons: MDK Baden-Wurttemberg versus MDK
      Westfalen-Lippe].
AB  - We report on the first detailed comparison of evaluation results regarding the
      correct billing in the G-DRG (German diagnosis-related group) system. For two
      Medical Review Boards of the Statutory Health Insurance Funds of comparable size
      (MDK Baden-Wurttemberg and MDK Westfalen-Lippe), we analysed consecutive
      expertises regarding correct billing according to section sign 275 SGB V, and the
      results were compared in terms of the frequency of DRG-relevant error codes,
      their relevance to revenue, and the question of error clustering (specific DRGs,
      primary diagnoses, etc.). The analysis comprised 51,010 individual expertises
      pertaining to billings of the year 2005 (admittance to hospital from January 1 to
      December 31, 2005). The proportion of disapproved cases was 38.5% in Baden
      Wurttemberg and 44.6% in Westfalen-Lippe. Among these, errors to the disadvantage
      of the Health Insurance (incorrectly high) were 33.9% and 39.3%, respectively,
      and errors to the disadvantage of the hospitals (incorrectly low) were 4.6% and
      5.3%, respectively. The resulting ratio (incorrectly high vs. low) was an
      identical 7.4 in both cases. Not only the most commonly rejected DRGs but also
      the primary and secondary diagnoses were similar in both cases, while the
      disapproved procedure codes showed a significant variability (analysis based on
      the respective 10 most common objections). We discuss the similarities and
      differences in these results and their possible causes, and demonstrate the cost
      relevance of this audit segment. Result comparisons of this type can yield
      insights into streamlining of the review practice of Medical Review Boards, as
      well as increase the efficiency and effectiveness of the selection of cases.

PMID- 17440844
TI  - [Chronic HCV infections. A model disease for therapy, economics and social
      medical aspects].
AB  - In Germany up to 800,000 persons are chronically infected with the hepatis C
      virus. This chronic disease is correlated with a significant morbidity and
      mortality. This is a consequence of the development of liver cirrhosis and
      hepatocellular carcinoma in a substantial proportion of the patients. Health
      quality of life is also affected by the infection. There are reliable standards
      available for diagnosis and treatment. Antiviral treatment is highly effective
      and the combination of pegylated interferon alpha with ribavirin leads to a
      sustained viral eradication in about 60% of the cases. The treatment is also cost
      effective and results in an increased life expectancy. Costs for HCV treatment
      are favourable in comparison to other well accepted therapies and interventions
      and a reduction of future costs can be expected.Thus, active screening for HCV
      infected persons should be intensified to improve the quality of medical care.
      Early and broad treatment is potentially able to reduce the future burden of HCV
      related diseases.

PMID- 17440845
TI  - [Bedtime, television and computer habits of primary school children in Germany].
AB  - BACKGROUND: Pediatricians recommend daily sleep of at least ten hours for
      children aged 9 and 10 years. Sufficient sleep is necessary for maintaining the
      body's homeostasis, as well as for fixing memories and learning. Lack of sleep in
      children has been associated with a diminished school performance, reduced
      attention span, and obesity. Adulthood is influenced by childhood lifestyle
      habits. Data from 4th graders in 34 schools in Mainz and its surroundings were
      analysed in order to determine negative health lifestyle factors in German
      primary school children, such as lack of sleep and increased leisure time spent
      watching television and computer gaming. METHODS: Data from a cross-sectional
      study regarding cellular phone use in fourth-graders in Mainz were used for this
      analysis. Bedtime, television and computer use habits, as well as other factors
      were explored. A total of 1933 children from 34 schools participated by answering
      a questionnaire in the 2002-2003 school year (participation rate: 88%). Complete
      data for the secondary analysis were available from 1889 students (51% male,
      median age 10 years). RESULTS: Overall, 28% of the children reported going to bed
      after 9 pm on week nights, 16% reported watching television more than three hours
      daily, and 11% played computer or video games more than three hours daily. In the
      adjusted binary logistic regression model, being older, male, having older
      siblings, watching television (OR 1.82, 95% CI 1.28-2.61) and playing computer
      games (OR 3.23; 95% CI 2.24-4.67) for more than three hours daily, owning a
      mobile phone, and being in a school in the city were associated with going to bed
      after 9 pm. CONCLUSION: Every fourth child does not obtain a sleep duration of 10
      hours, under the assumption that primary schoolchildren need to be awake at 7 am
      on weekdays. Lifestyle factors that may negatively influence a child's
      development determine their actual and future habits. Sufficient sleep and less
      television and computer leisure times should be assertively emphasized to parents
      and carers of primary school students, in order to prevent the negative
      consequences of lack of sleep, such as diminished school performance. Developing
      sex-specific prevention programs, which take into account the complex lifestyles
      and habits of primary schoolchildren, seems to be relevant.

PMID- 17440846
TI  - [Alfred Grotjahn's (1869-1931) way to "Faustic pact" in his project on social
      hygiene].
AB  - The purpose of this paper in historiographic research is to show the relation of
      social hygiene to demography. The study focuses on Alfred Grotjahn's merits in
      the establishment of an independent profile on social hygiene in Germany at the
      beginning of the 20th century. Grotjahn realised early that demography or,
      respectively, population statistics is a directing force for a new formation and
      reorganisation of social hygiene, recognising the meaning of demography for the
      realm of social hygiene. Grotjahn integrated practical eugenics as a part of
      reproduction hygiene through the generative aspect within his planning horizon.
      This resulted in Grotjahn's "Faustic pact" with eugenics. In the history of the
      reception of Grotjahn's concept of social hygiene it was his pact with eugenics
      that took him in the dock as an intellectual promoter of national socialist
      politics. But the problem that Grotjahn left is still being under discussion even
      70 years after his death: Is a control and limitation of technocratic social
      hygiene orientated towards elementary human rights possible or is it at all
      desirable?

PMID- 17440847
TI  - Endoscopic removal of a bladder calculus via flexible sigmoidoscopy.

PMID- 17440848
TI  - Bleeding - not always a sign of relapse of long-standing colitis.

PMID- 17440849
TI  - Long-term follow-up after endoscopic forceps biopsies for early stage duodenal
      carcinoid: case report and review of endoscopic treatments.

PMID- 17440850
TI  - Diffuse esophageal parakeratosis.

PMID- 17440851
TI  - Percutaneous endoscopic gastrostomy with the aid of a colonoscope to avoid
      gastrocolic fistula formation.

PMID- 17440852
TI  - Use of proton pump inhibitors may cause squamous epithelial masking of
      intramucosal carcinoma in Barrett's esophagus.

PMID- 17440853
TI  - Depressed-type early duodenal carcinoma (carcinoma in situ) observed by enhanced
      magnification endoscopy.

PMID- 17440854
TI  - Chlamydia trachomatis proctitis.

PMID- 17440855
TI  - Gemella morbillorum mediastinitis and osteomyelitis following transesophageal
      endoscopic ultrasound-guided fine-needle aspiration of a posterior mediastinal
      lymph node.

PMID- 17440856
TI  - Self-expandable metal stents placed with overtube for the treatment of malignant
      obstruction of the gastrointestinal tract in 33 consecutive patients.

PMID- 17440857
TI  - Thoracic myelolipoma diagnosed by endoscopic ultrasonography and fine-needle
      aspiration cytology.

PMID- 17440858
TI  - Esophagitis dissecans: a rare cause of odynophagia.

PMID- 17440859
TI  - Endoscopic treatment of completely occluding anastomotic web using incision and
      ballooning after dye injection.

PMID- 17440860
TI  - Jejunal inflammatory granuloma: a complication of direct percutaneous endoscopic
      jejunostomy.

PMID- 17440861
TI  - Endoscopic extraction of Fasciolopsis buski.

PMID- 17440862
TI  - Metal stent migration after chemotherapy.

PMID- 17440863
TI  - Pneumoperitoneum after argon plasma coagulation treatment: perforation or
      accumulation of air in the cavity?

PMID- 17440864
TI  - Dancing hookworm in the small bowel detected by capsule endoscopy: a synthesized
      video.

PMID- 17440865
TI  - Bacterial meningitis following upper gastrointestinal endoscopy in patients with
      cirrhosis - bear it in mind.

PMID- 17440866
TI  - Tumorous neo-vascularization: a newly recognized endoscopic feature of intestinal
      non-Hodgkin lymphoma.

PMID- 17440867
TI  - Diagnosis of an unusual tumor in the duodenum.

PMID- 17440868
TI  - Acute abdominal pain caused by a prolapsed duodenal polyp that resolved when the
      polyp broke off spontaneously.

PMID- 17440869
TI  - Esophagitis dissecans superficialis associated with bisphosphonates.

PMID- 17440870
TI  - Pneumoscrotum after colonoscopic polypectomy.

PMID- 17440871
TI  - Intraductal tubular adenoma, pyloric gland-type, of the pancreas.

PMID- 17440872
TI  - Portal vein embolization as a complication of Histoacryl injection for a bleeding
      giant gastric ulcer.

PMID- 17440873
TI  - Capsule endoscopy findings in intestinal follicular lymphoma.

PMID- 17440874
TI  - An unusual foreign body in the transverse colon.

PMID- 17440875
TI  - Ileal metastasis from thoracic melanoma disclosed by video capsule endoscopy: an
      unusual but not extraordinary source of obscure bleeding.

PMID- 17440876
TI  - Double pylorus: strong evidence for the acquired etiology of this rare
      abnormality.

PMID- 17440877
TI  - Intramural duodenal hematoma as a complication of pancreatic cancer.

PMID- 17440878
TI  - Gastritis cystica profunda in a patient with no history of gastric surgery.

PMID- 17440879
TI  - Endoscopic ultrasound-guided fine-needle aspiration of enlarged mediastinal lymph
      nodes in eosinophilic esophagitis.

PMID- 17440880
TI  - A new endoscopic therapy for an intraluminal diverticulum of the duodenum.

PMID- 17440881
TI  - Invagination of the muscularis propria in a polyp stalk: a rare cause of post
      polypectomy perforation of the colon.

PMID- 17440882
TI  - [Breathing disorders during sleep. Introduction].

PMID- 17440883
TI  - [Neurobiology of sleep].

PMID- 17440884
TI  - [Mechanisms and pathophysiology of obstructive sleep apnea].

PMID- 17440885
TI  - [Classification, clinical picture and diagnosis of sleep disordered breathing].

PMID- 17440886
TI  - [The familial occurrence of obstructive sleep apnea syndrome].

PMID- 17440887
TI  - [Obstructive sleep apnea in children].

PMID- 17440888
TI  - [CPAP therapy for patients with OSAS].

PMID- 17440889
TI  - [Head and neck surgery in the management of obstructive sleep apnea syndrome].

PMID- 17440890
TI  - [Oral appliances for patients with OSAS].

PMID- 17440891
TI  - [Principles of nutrition and pharmacotherapy of obesity in patients with
      obstructive sleep apnea].

PMID- 17440892
TI  - [The role of bariatric surgery in the treatment of obstructive sleep apnea].

PMID- 17440893
TI  - [Cardiac diseases--complications in patients with OSA].

PMID- 17440894
TI  - [Obstructive sleep apnea and systemic hypertension].

PMID- 17440895
TI  - [Neurological disorders in patients with obstructive sleep apnea (OSA)].

PMID- 17440896
TI  - [Endocrine disorders related to obstructive sleep apnea syndrome].

PMID- 17440898
TI  - [Emotions, cognitive functions and quality of life in OSAS patients].

PMID- 17440897
TI  - [Disturbances of respiration during sleep and automobile crashes].

PMID- 17440899
TI  - [Hypersomnias of central origin].

PMID- 17440900
TI  - The role of death qualification and need for cognition in venirepersons'
      evaluations of expert scientific testimony in capital trials.
AB  - The purpose of this study was to investigate the role of death qualification in
      venirepersons' evaluations of expert scientific testimony in capital trials. 200
      venirepersons from the 12th Judicial Circuit in Bradenton, FL completed a booklet
      that contained the following: one question that measured their attitudes toward
      the death penalty; one question that categorized their death-qualification
      status; the Need for Cognition (NFC) scale (Cacioppo, Petty & Kao, 1984); a
      summary of the guilt phase of a capital case (which included the cross
      examination of the state's expert witness); verdict preference; five questions
      concerning participants' evaluations of the expert's testimony; the penalty phase
      of a capital case; sentence preference; and standard demographic questions.
      Results indicated that death-qualified venirepersons were more likely to
      demonstrate a low need for cognition and view ambiguous expert scientific
      testimony as valid, important in their decision-making processes, unbiased, and
      of high quality. Finally, death-qualified participants were more conviction- and
      death- prone than their excludable counterparts. Surprisingly, death-qualified
      and excludable jurors did not differ with respect to whether or not they felt
      that the expert followed correct procedures. Legal implications and applications
      are discussed.

PMID- 17440901
TI  - Multiplicity editing including quaternary carbons: improved performance for the
      13C-DEPTQ pulse sequence.
AB  - An improved version of the DEPTQ experiment yielding the signal and multiplicity
      information for all carbon types including the signals of quaternary carbons is
      proposed. It encompasses all the known advantages of the basic DEPT experiment.
      In comparison to the original version, signals of the sensitivity-limiting
      quaternary carbons are markedly increased: the initial 13C pulse may be adjusted
      to the Ernst angle, the NOE build-up period is prolonged by the split relaxation
      delay and a partial recovery of signal losses due to instrumental imperfections
      is achieved by the incorporation of composite adiabatic 13C refocussing pulses.
      Furthermore, pure absorption lineshapes for all carbon types are obtained with
      only one single scan. These attributes make this experiment attractive for 13C
      analysis of small molecules (including spectral editing), particularly in high
      throughput analysis laboratories.

PMID- 17440902
TI  - Novel amphiphilic ternary polysaccharide derivates chitosan-g-PCL-b-MPEG:
      synthesis, characterization, and aggregation in aqueous solution.
AB  - Chitosan-g-PCL-b-MPEG copolymers of various compositions were successful
      synthesized via a protection-graft-deprotection procedure, by the esterification
      of phthaloyl-protected chitosan (PHCS) with MPEG-b-PCL-COOH, which was
      synthesized from MPEG and epsilon-caprolactone and carboxylated by maleic
      anhydride. The chemical structure of the chitosan-g-PCL-b-MPEG was characterized
      by Fourier transform infrared and NMR spectroscopy. The chitosan-g-PCL-b-MPEG was
      obtained as amphoteric hybrid with amino polysaccharide backbone and amphiphilic
      MPEG-b-PCL side chain. Their crystallinity and aggregation behavior in aqueous
      solution were also investigated.

PMID- 17440903
TI  - Study of intramolecular competition between carboxylate and phosphonate for
      Pt(II) with the aid of a novel tridentate carboxylato-thioether-phosphonato
      ligand.
AB  - The tridentate dianionic ligand 2-[2'
      (hydroxyisopropoxyphosphoryl)phenylsulfanyl]benzoate (L(2-)) reacts with cis
      [Pt(NH(3))(2)(H(2)O)(2)](2+) to form an S,O-chelate in which the O-coordinated
      group is either carboxylate or phosphonate, depending on the degree of
      protonation of the complex. Carboxylate appears to be the stronger ligand, and
      the stoichiometric reaction between cis-[Pt(NH(3))(2)(H(2)O)(2)](2+) and L(2-)
      yields the neutral species [Pt(L)(NH(3))(2)], with L bound by sulfanyl and
      carboxylate groups, both in solution and in the solid state. Upon protonation of
      [Pt(L)(NH(3))(2)], the stronger basicity of the carboxylate causes the Pt
      coordination to switch from carboxylate to phosphonate, and the uncoordinated
      carboxylate group becomes protonated. In methanolic solution, the first-order
      kinetics of this rearrangement could be observed by (31)P NMR spectroscopy. Both
      complexes-the carboxylate-bound neutral complex [Pt(L)(NH(3))(2)].H(2)O
      (triclinic, P1 (no. 2), a=9.529(6), b=9.766(6), c=12.299(7) angstroms,
      alpha=106.91(2), beta=101.71(2), gamma=102.05(2) degrees, Z=2) and the
      perchlorate salt of the phosphonate-bound complex [Pt(LH)(NH(3))(2)]ClO(4).H(2)O
      (monoclinic, P2(1)/c (no. 14), a=12.095(2), b=14.046(2), c=14.448(2) angstroms,
      beta=95.55(2) degrees, Z=4)-were characterized by X-ray crystallography.

PMID- 17440904
TI  - Sodium cation migration above the diimine pi-system of solvent coordinated dpp
      BIAN sodium aluminum complexes (dpp-BIAN=1,2-bis[(2,6
      diisopropylphenyl)imino]acenaphthene).
AB  - The reactions of the disodium salt of the 1,2-bis[(2,6
      diisopropylphenyl)imino]acenaphthene (dpp-BIAN) ligand with one equivalent of
      Me2AlCl in diethyl ether, toluene, and benzene produced the complexes
      [Na(Et2O)2(dpp-BIAN)AlMe2] (1), [Na(eta6-C7H8)(dpp-BIAN)AlMe2] (2) and [Na(eta6
      C6H6)(dpp-BIAN)AlMe2] (3), respectively. Recrystallization of 1 from hexane
      afforded solvent-free [{Na(dpp-BIAN)AlMe2}n] (4) or [Na(Et2O)(dpp-BIAN)AlMe2] (5)
      depending on the temperature of the solvent. The molecular structures of 1-5 have
      been determined by single-crystal X-ray diffraction. The sodium cation
      coordinates either one of the naphthalene rings (1) or the diimine part of the
      dpp-BIAN ligand (2-5). In the complexes 2 and 3, the sodium cation additionally
      coordinates the toluene (2) or benzene molecule (3) in an eta6-fashion.

PMID- 17440905
TI  - Total synthesis of potent antifungal marine bisoxazole natural products
      bengazoles A and B.
AB  - The bengazoles are a family of marine natural products that display potent
      antifungal activity and a unique structure, containing two oxazole rings flanking
      a single carbon atom. Total syntheses of bengazole A and B are described, which
      contain a sensitive stereogenic centre at this position between the two oxazoles.
      Additionally, the synthesis of 10-epi-bengazole A is reported. Two parallel
      synthetic routes were investigated, relying on construction of the 2,4
      disubstituted oxazole under mild conditions and a diastereoselective 1,3-dipolar
      cycloaddition. Our successful route is high yielding, provides rapid access to
      single stereoisomers of the complex natural products and allows the synthesis of
      analogues for biological evaluation.

PMID- 17440906
TI  - Intramolecular mixed-valence state through silicon or germanium double bridges in
      rigid bis(tetrathiafulvalenes).
AB  - The synthesis and characterization of two ortho-dimethyltetrathiafulvalene (o
      DMTTF)-based rigid dimers containing dimethylsilicon (Me(2)Si) or
      dimethylgermanium (Me(2)Ge) linkers are described. Single-crystal X-ray analysis
      reveals planar geometry for the central 1,4-disilicon or 1,4-digermanium six
      membered rings. DFT calculations provide optimized conformations in agreement
      with the experimental ones, and also emphasize the role of the heteroatomic
      linkers in the conjugation between the two redox active units. Cyclic voltammetry
      measurements show sequential oxidation into radical cation, and then dication
      species. Solution EPR measurements on the radical-cation species indicate full
      delocalization of the unpaired electron over both electroactive TTF units, with
      an associated coupling of 0.42 G with twelve equivalent protons. DFT calculations
      afford fully planar geometry for the radical-cation species and confirm the
      experimental isotropic coupling constant. Single-crystal X-ray analyses of two
      charge-transfer compounds obtained upon chemical oxidation, formulated as
      [(Me(2)Si)(2)(o-DMTTF)(2)].1/2[TCNQ].1/2[TCNQF(4)] and [(Me(2)Ge)(2)(o
      DMTTF)(2)].[TCNQ], demonstrate the occurrence of genuine mixed-valence radical
      cation species, as well as a three-dimensional network of short S...S
      intermolecular contacts. Temperature-dependent conductivity measurements
      demonstrate semiconducting behavior for both charge-transfer compounds, with an
      increase of the absolute value of the conductivity upon applying external
      pressure. Band structure calculations reveal peculiar pseudo-two-dimensional
      electronic structures, also confirming electronic interactions through SiMe(2)
      and GeMe(2) bridges.

PMID- 17440907
TI  - 51V NMR chemical shifts calculated from QM/MM models of vanadium
      chloroperoxidase.
AB  - (51)V NMR chemical shifts calculated from QM/MM-optimized (QM=quantum mechanical;
      MM=molecular mechanical) models of vanadium-dependent chloroperoxidase (VCPO) are
      presented. An extensive number of protonation states for the vanadium cofactor
      (active site of the protein) and a number of probable positional isomers for each
      of the protonation states are considered. The size of the QM region is increased
      incrementally to observe the convergence behavior of the (51)V NMR chemical
      shifts. A total of 40 models are assessed by comparison to experimental solid
      state (51)V NMR results recently reported in the literature. Isotropic chemical
      shifts are found to be a poor indicator of the protonation state; however,
      anisotropic chemical shifts and the nuclear quadrupole tensors appear to be
      sensitive to changes in the proton environment of the vanadium nuclei. This
      detailed investigation of the (51)V NMR chemical shifts computed from QM/MM
      models provides further evidence that the ground state is either a triply
      protonated (one axial water and one equatorial hydroxyl group) or a doubly
      protonated vanadate moiety in VCPO. Particular attention is given to the
      electrostatic and geometric effects of the protein environment. This is the first
      study to compute anisotropic NMR chemical shifts from QM/MM models of an active
      metalloprotein for direct comparison with solid-state MAS NMR data. This
      theoretical approach enhances the potential use of experimental solid-state NMR
      spectroscopy for the structural determination of metalloproteins.

PMID- 17440908
TI  - Substrate profile analysis and ACP-mediated acyl transfer in Streptomyces
      coelicolor Type III polyketide synthases.

PMID- 17440909
TI  - Ligand-induced folding of the adenosine deaminase A-riboswitch and implications
      on riboswitch translational control.
AB  - By using a structure-based fluorescence spectroscopic approach, we have examined
      the folding of an adenine-responsive riboswitch that regulates translation
      initiation. We observed adaptive recognition of the ligand for the aptamer domain
      of adenosine deaminase (add) mRNA from Vibrio vulnificus, and revealed pronounced
      conformational changes even in the preorganized loop-loop region that is distant
      from the binding site. Importantly, the full-length riboswitch domain, which has
      a potential translational repressor stem is able to form a binary complex with
      adenine, and does not act as a folding trap to inhibit binding. The aptamer that
      is extended by the expression platform therefore remains fully responsive to its
      ligand; this is in contrast to the previously investigated pbuE A-riboswitch,
      which becomes trapped in a nonresponsive terminator fold. Consequently, the
      latter must employ complex response mechanisms, such as operating in kinetic
      control mode or using transcriptional pausing, to provide time for the aptamer
      portion to fold and to bind. The different behavior of the riboswitches can be
      rationalized by their distinct sequence interface between the aptamer and
      expression platform. For the add A-riboswitch, our data suggest a
      thermodynamically driven response mechanism.

PMID- 17440910
TI  - Light-stimulated patterning of cells.

PMID- 17440911
TI  - [4+1]/[2+1] Cycloaddition reactions of Fischer carbene complexes with alpha,beta
      unsaturated ketones and aldehydes.

PMID- 17440912
TI  - Bacterial exopolysaccharides--a perception.
AB  - Microbial polysaccharides are multifunctional and can be divided into
      intracellular polysaccharides, structural polysaccharides and extracellular
      polysaccharides or exopolysaccharides (EPS). Extracellular polymeric substances
      (EPS), produced by both prokaryotes (eubacteria and archaebacteria) and
      eukaryotes (phytoplankton, fungi, and algae), have been of topical research
      interest. Newer approaches are carried out today to replace the traditionally
      used plant gums by their bacterial counterparts. The bacterial exopolysaccharides
      represent a wide range of chemical structures, but have not yet acquired
      appreciable significance. Chemically, EPS are rich in high molecular weight
      polysaccharides (10 to 30 kDa) and have heteropolymeric composition. They have
      new-fangled applications due to the unique properties they possess. Owing to
      this, exopolysaccharides have found multifarious applications in the food,
      pharmaceutical and other industries. Hence, the present article converges on
      bacterial exopolysaccharides.

PMID- 17440913
TI  - Effect of stress on growth, pigment production and morphology of Monascus sp. in
      solid cultures.
AB  - The aim of the current work was to study the influence of stress on pigment
      production in Monascus purpureus under solid-state fermentation. Thermal stress
      was induced by incubating the culture at various high temperatures. For giving
      osmotic stress, different concentration of NaCl and glycerol were added to the
      solid substrate prior to autoclaving. Morphological studies were done by light
      microscopy and scanning electron microscopy. When the cells were exposed to high
      temperature, high glycerol and salt concentration, significant changes in pigment
      production and growth were observed. High temperature (>45 degrees C) induced the
      production of more yellow pigments. High concentration of NaCl induced
      conidiation and caused a decrease in fungal biomass (up to 50%) but red pigment
      production increased from 11.86 OD/gds to 20.14 OD/gds. When subjected to
      glycerol stress, a significant increase in aerial mycelia was observed when
      compared with the control conditions. The results attain significance for
      exploiting the fungal culture of Monascus purpureus LPB 97 for producing colors
      of choice--red, or yellow, or increasing the yield of red pigments considerably.
      Thus, these results could well impact the commercial aspect of Monascus pigments
      for industrial application.

PMID- 17440914
TI  - Laccase production by the white-rot fungus Termitomyces clypeatus.
AB  - Laccase was detected in the culture filtrate of white-rot fungus Termitomyces
      clypeatus. The enzyme was found at the late phase of submerged growth in a medium
      containing glucose or cellulose as the carbon source. The present study indicates
      that laccase produced by T. clypeatus is an intracellular enzyme, released in the
      medium due to cell lysis at the end of the growing phase. Laccase produced by T.
      clypeatus is different from the extracellular polyphenol oxidase of T.
      albuminosus, also produced at the late phase of growth. This is the first report
      of laccase production by a Termitomyces sp.

PMID- 17440915
TI  - Expression and characterization of the chaperonin molecular machine from the
      hyperthermophilic archaeon Pyrococcus furiosus.
AB  - The chaperonin molecular machine from hyperthermophilic archaeon Pyrococcus
      furiosus was studied in this paper. The Pyrococcus furiosus chaperonin gene
      (PfCPN) was amplified by PCR from the Pyrococcus furiosus genomic DNA, and
      expressed in Escherichia coli BL21-Codonplus(DE)(3)-RIL. The recombinant PfCPN
      was purified to homogeneity by using ion-exchange and size-exclusion
      chromatography. It was found that the ATPase activity of the PfCPN was highest at
      88 degrees C, and there existed a nested cooperativity of the ATPase activity of
      the PfCPN. This result suggested that nested allosteric behavior may be common to
      chaperonin molecular machines from archaea. The half-life (t(1/2)) of the ATPase
      activity of the PfCPN at 100 degrees C was about 60 min. The PfCPN displayed
      chaperone activity in preventing lysozyme from thermal inactivation. This
      chaperone activity was in an ATP-dependent manner.

PMID- 17440916
TI  - Esterases and putative lipases from tropical isolates of Aureobasidium pullulans.
AB  - Esterases and lipases have been studied in a number of fungi, though very little
      is known about esterases from Aureobasidium pullulans especially from the African
      tropics. In this study, forty-two Zimbabwean isolates were screened for lipase
      activity on tributyrin agar. Extracellular esterase activities of seven selected
      isolates were studied under varying conditions using para-nitrophenol acetate as
      substrate. Twenty isolates (48%) showed lipolytic activity; sixteen showed
      negative results for lipase activity while the rest showed weak activities.
      Esterase activities in broth cultures ranged from 0.011-0.223 mmol/microg
      protein/min while activities ranged from 1.5-12.8 U/ml under solid state
      fermentation. The esterases were optimally active at pH 7.6-8.0, showed a
      temperature optimum of 35 degrees C and retained more than 50% activity at
      temperatures up to 60 degrees C and at pH 4.0-7.0 after 150 min. Enzyme
      production was optimal after 5-6 days with diammonium hydrogen phosphate as
      nitrogen source. Isolates showed variations in preference for carbon source for
      esterase production. The A. pullulans esterases differed from most fungal
      esterases in that they are optimally active in alkaline conditions and are active
      over a broad pH range.

PMID- 17440917
TI  - PCR monitoring of Lactobacillus and Bifidobacterium dynamics in fermentations by
      piglet intestinal microbiota.
AB  - A new group-specific primer (Lact71R), targeting the 16S-23S rDNA intergenic
      spacer region of Lactobacillus, was tested in its specificity to amplify rDNA of
      lactobacilli from piglet intestinal origin by polymerase chain reaction (PCR).
      Lact71R and Lab0677F, a Lactobacillus group-specific primer targeting the 16S
      rDNA, generated a common amplicon by PCR with DNA from Lactobacillus and
      Pediococcus reference strains, but not from Weissella strains. Sequence analysis
      of clones obtained by PCR amplification with Lact71R and Lab0677F and total DNA
      isolated from the ileal, caecal and colonic contents of one piglet resulted in
      Lactobacillus and Lactobacillus-like sequences mainly retrieved from intestinal
      environments. The primer pair was further validated in a culture independent PCR
      analysis to monitor broad fluctuations of lactobacilli populations in fructo
      oligosaccharides (FOS) fermentations by piglet intestinal microbiota.
      Bifidobacterium genus-specific primers were also used for PCR titre determination
      throughout FOS fermentations, in parallel with lactate and short chain fatty
      acids (SCFA) quantification. Increases between PCR titres were correlated with
      lactate detection in early stages of fermentation. Based on the obtained results,
      a simple monitoring PCR approach is proposed, foreseeing its application to the
      study of the dynamics of specific bacterial populations in complex environments.

PMID- 17440918
TI  - Antimicrobial activity of some Australian plant species from the genus
      Eremophila.
AB  - Plant species of the genus Eremophila (Myoporaceae) are native to Australia and
      are known to produce a diverse range of unusual secondary compounds. The purpose
      of this research was to examine the antimicrobial activity of 72 Eremophila
      species most of which had not been the subject of any previous pharmacological
      testing. Organic extracts of Eremophila species were screened for antimicrobial
      activity against Gram-positive and Gram-negative bacteria and yeasts of medical
      importance. Extracts of a number of Eremophila species showed selective activity
      against Gram-positive bacteria with MICs for the most active species in the range
      of 16 to 62 microg/ml for Streptococcus species, and 62 to 250 microg/ml for
      standard strains of Staphylococcus aureus. Extracts with the greatest activity
      against standard strains were tested against 68 clinical isolates of multi
      resistant methicillin-resistant S. aureus (mMRSA). The majority of the clinical
      isolates were susceptible to concentrations below 62.5 microg/ml for the extracts
      of E. drummondii, E. linearis, E. serrulata, E. acrida, E. neglecta, E. virens
      and a new undescribed species affiliated with E. prolata. The extract of E.
      virens inhibited growth of all 68 clinical mMRSA isolates at the minimum tested
      concentration of 31 microg/ml. This study has shown for the first time that a
      number of different Eremophila species manifest selective antibacterial activity
      against Gram-positive organisms which are important causes of human disease. It
      shows that there are several Eremophila species possessing interesting
      antibacterial activity besides those that have published traditional use. These
      may yield novel antibacterial compounds with potential to be used in biomedical
      applications.

PMID- 17440919
TI  - Regulation of the pyrimidine biosynthetic pathway in a pyrD knockout mutant of
      Pseudomonas aeruginosa.
AB  - In research to date, regulation of the pyrimidine biosynthetic pathway at the
      level of gene expression has not been shown for wild type Pseudomonas aeruginosa.
      No repression was observed when uracil was added to the growth medium nor was any
      derepression seen when Pyr(-) auxotrophs were limited for pyrimidines. Here we
      show that the addition of uracil to Pseudomonas minimal medium influenced the
      synthesis of pyrimidine enzymes, while starvation of a pyrimidine knockout mutant
      (pyrD) elicited derepression of the pyrimidine enzymes. Moreover, the inclusion
      of orotate in the growth medium induced the synthesis of dihydroorotase in both
      wild type and mutant. These results suggest that the pyrimidine pathway in P.
      aeruginosa is regulated at the level of enzyme synthesis in a manner similar to a
      number of other Pseudomonas species.

PMID- 17440920
TI  - Potential of the adhesion of bacteria isolated from drinking water to materials.
AB  - Heterotrophic bacteria (11 genera, 14 species, 25 putative strains) were isolated
      from drinking water, identified either biochemically or by partial 16s rDNA gene
      sequencing and their adherence characteristics were determined by two methods: i.
      thermodynamic prediction of adhesion potential by measuring hydrophobicity
      (contact angle measurements) and ii. by measuring adherence to eight different
      substrata (ASI 304 and 316 stainless steel, copper, polyvinyl chloride,
      polypropylene, polyethylene, silicone and glass). All the test organisms were
      hydrophilic and inter-species variation in hydrophobicity occurred only for
      Comamonas acidovorans. Stainless steel 304 (SS 304), copper, polypropylene (PP),
      polyethylene (PE) and silicone thermodynamically favoured adhesion for the
      majority of test strains (>18/25), whilst adhesion was generally less
      thermodynamically favorable for stainless steel 316 (SS 316), polyvinyl chloride
      (PVC) and glass. The predictability of thermodynamic adhesion test methods was
      validated by comparison with 24-well microtiter plate assays using nine reference
      strains and three adhesion surfaces (SS 316, PVC and PE). Results for
      Acinetobacter calcoaceticus, Burkolderia cepacia and Stenotrophomonas maltophilia
      sp. 2 were congruent between both methods whilst they differed for the other
      bacteria to at least one material. Only A. calcoaceticus had strongly adherent
      properties to the three tested surfaces. Strain variation in adhesion ability was
      detected only for Sphingomonas capsulata. Analysis of adhesion demonstrated that
      in addition to physicochemical surface properties of bacterium and substratum,
      biological factors are involved in early adhesion processes, suggesting that
      reliance on thermodynamic approaches alone may not accurately predict adhesion
      capacity.

PMID- 17440921
TI  - Isolation and characterization of lactic acid bacteria from lakes.
AB  - Lactic acid bacteria (LAB) were isolated from lake-water samples collected at 7
      lakes distributed in Yamanashi prefecture, Japan. Sampling was performed year
      round. 112 cultures were isolated and divided into classes by phenotype and then
      into groups by restriction fragment length polymorphism analysis and sequencing
      of 16S ribosomal DNA. Phenotypic and biochemical characteristics identified
      eleven different bacterial groups (A to K), and the results showed that the
      isolates represented seven genera: Lactococcus, Leuconostoc, Enterococcus,
      Lactobacillus, Carnobacterium, Streptococcus, and Weissella. Lactococcus lactis
      subsp. lactis was the most abundant lactic acid bacteria found in these lakes.
      Furthermore, Lactococcus lactis subsp. lactis was also the most abundant lactic
      acid bacteria found throughout the year. Seasonal differences, numbers of
      isolates and the species of lactic acid bacteria were also recorded in this
      study.

PMID- 17440922
TI  - New phenyl-ethanediols from the culture broth of Boletus edulis.
AB  - A new phenyl-ethanediol, (1S)-(4-acetylphenyl)-1, 2-ethanediol (1), and a new
      natural product, (1S)-(3-ethenylphenyl)-1, 2-ethanediol (2), were isolated from
      the culture broth of the basidiomycete Boletus edulis together with three related
      known compounds, 1-(4-ethylphenyl)-1, 2-ethanediol (3), 1-(3-ethylphenyl)-1, 2
      ethanediol (4) and 1-(3-formylphenyl)-ethanone (5). Their structures were
      elucidated by spectroscopic methods including extensive 2D-NMR techniques.

PMID- 17440923
TI  - Alcohol consumption and risk of bladder cancer in Los Angeles County.
AB  - The role of alcoholic beverages in bladder carcinogenesis is still unclear, with
      conflicting evidence from different studies. We investigated the relationship
      between alcohol consumption and bladder cancer, and the potential interaction
      between alcohol consumption and other exposures. In a population-based case
      control study conducted in Los Angeles County, 1,586 pairs of cases and their
      matched neighborhood controls were interviewed. Data were analyzed to determine
      whether bladder cancer risk differs by alcohol consumption, and whether different
      alcoholic beverages have different effects. The risk of bladder cancer decreased
      with increasing frequency (p for trend = 0.003) and duration of alcohol
      consumption (p for trend = 0.017). Subjects who drank more than 4 drinks per day
      had a 32% lower (odds ratio, 0.68; 95% confidence interval, 0.52-0.90) risk of
      bladder cancer than those who never drank any alcoholic beverage. Beer (p for
      trend = 0.002) and wine (p for trend = 0.054) consumption were associated with
      reduced risk of bladder cancer, while hard liquor was not. The reduction in risk
      was mostly seen among shorter-term smokers who urinated frequently. Alcohol
      consumption was strongly associated with a reduced risk of bladder cancer. The
      effect was modified by the type of alcoholic beverage, cigarette smoking and
      frequency of urination.

PMID- 17440924
TI  - The murine allantois: emerging paradigms in development of the mammalian
      umbilical cord and its relation to the fetus.
AB  - The fertilized egg of the mammal gives rise to the embryo and its extraembryonic
      structures, all of which develop in intimate relation with each other. Yet,
      whilst the past several decades have witnessed a vast number of studies on the
      embryonic component of the conceptus, study of the extraembryonic tissues and
      their relation to the fetus have been largely ignored. The allantois, precursor
      tissue of the mature umbilical cord, is a universal feature of all placental
      mammals that establishes the vital vascular bridge between the fetus and its
      mother. The allantois differentiates into the umbilical blood vessels, which
      become secured onto the chorionic component of the placenta at one end and onto
      the fetus at the other. In this way, fetal blood is channeled through the
      umbilical cord for exchange with the mother. Despite the importance of this
      vascular bridge, little is known about how it is made. The aim of this review is
      to address current understanding of the biology of the allantois in the mouse and
      genetic control of its features and functions, and to highlight new paradigms
      concerning the developmental relationship between the fetus and its umbilical
      cord.

PMID- 17440925
TI  - Chromosome 8 BAC array comparative genomic hybridization and expression analysis
      identify amplification and overexpression of TRMT12 in breast cancer.
AB  - Genomic changes in chromosome 8 are commonly observed in breast cancer cell lines
      and tumors. To fine map such genomic changes by comparative genomic hybridization
      (CGH), a high resolution (100 kb) chromosome 8 array that can detect single copy
      changes was developed using Phi29 DNA polymerase amplified BAC (bacterial
      artificial chromosome) DNA. The BAC array CGH resolved the two known amplified
      regions (8q21 and 8q24) of a breast cancer cell line (SKBR3) into nine separate
      regions including six amplicons and three deleted regions, all of which were
      verified by Fluorescence in situ hybridization. The extent of the gain/loss for
      each region was validated by qPCR. CGH was performed with a total of 8 breast
      cancer cell lines, and common regions of genomic amplification/deletion were
      identified by segmentation analysis. A 1.2-Mb region (125.3-126.5 Mb) and a 1.0
      Mb region (128.1-129.1 Mb) in 8q24 were amplified in 7/8 cell lines. A global
      expression analysis was performed to evaluate expression changes associated with
      genomic amplification/deletion: a novel gene, TRMT12 (at 125.5 Mb), amplified in
      7/8 cell lines, showed highest expression in these cell lines. Further analysis
      by RT-qPCR using RNA from 30 breast tumors showed that TRMT12 was overexpressed
      >2 fold in 87% (26/30) of the tumors. TRMT12 is a homologue of a yeast gene
      encoding a tRNA methyltransferase involved in the posttranscriptional
      modification of tRNA(Phe), and exploring the biological consequence of its
      altered expression, may reveal novel pathways in tumorigenesis. This article
      contains Supplementary Material available at
      http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

PMID- 17440926
TI  - Increased toll-like receptor 9 expression in cervical neoplasia.
AB  - Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns
      (PAMPs) and enable innate immune responses. Although TLR9 has been previously
      considered to be expressed only in immune cells, there is now increasing evidence
      that TLR9 expression is present in nonimmune cells as well. In this study, we
      undertook to determine whether TLR9 expression was associated with disease
      progression in cervical neoplasia. TLR9 expression was evaluated by
      immunohistochemistry in 55 formalin-fixed paraffin-embedded cervical tissues;
      nine normal cervical specimens, 10 low-grade cervical intraepithelial neoplasias
      (CINs), 12 high-grade CINs, and 24 invasive squamous cell carcinomas (ISCCs). In
      addition, TLR9 expression was evaluated, at the RNA level, in fresh frozen
      cervical carcinoma tissues by real-time quantitative RT-PCR. Immunohistochemical
      staining showed that TLR9 expression was undetectable (55.6%) or weak (44.4%) in
      normal cervical squamous epithelial tissues, however, variable staining was
      observed in the basal layer of all normal endocervical glands. TLR9 expression,
      which was mainly observed as cytoplasmic staining, gradually increased in
      accordance with the histopathological grade in the following order: low-grade
      CIN<high-grade CIN<ISCC (P<0.001), and in particular, was moderate to strong in
      70% of ISCC cases. Furthermore, real-time quantitative RT-PCR revealed that TLR9
      expression, in tumors, was significantly enhanced compared to normal cervical
      tissues (P=0.012). These results suggest that TLR9 may play a significant role in
      tumor progression of cervical neoplasia and may represent a useful marker for
      malignant transformation of cervical squamous cells.

PMID- 17440927
TI  - Synergistic effects of multiple treatments, and both DNA and RNA direct bindings
      on, green tea catechins.
AB  - This article reviews two main topics: (1) the synergistic effects of multiple
      treatments with green tea catechin and (2) the direct binding of (-)
      epigallocatechin gallate (EGCG) to both DNA and RNA molecules. Japanese drink
      green tea throughout the day, so we studied whether multiple treatments of cells
      with EGCG would enhance the expression of apoptosis-related genes, such as growth
      arrest and DNA damage-inducible gene (GADD153) and cyclin-dependent kinase
      inhibitor gene (p21(waf1)): The results suggest that the synergistic enhancement
      of both GADD153 and p21(waf1) gene expressions by multiple treatments plays a
      significant role in human cancer prevention with green tea beverage. Our previous
      observation-that nucleic acids extracted from catechin-treated cells are colored
      allowed us to speculate that catechins directly interact with nucleic acids.
      Surface plasmon resonance assay (Biacore) indicated that four catechins, EGCG, (
      )-epicatechin gallate (ECG), (+)-gallocatechin gallate (GCG), and (+)-catechin
      gallate (CG), bound to DNA oligomers. Cold spray ionization mass spectrometry
      (CSI-MS) analysis showed that one to three EGCG molecules bound to single
      stranded 18 mers of DNA and RNA. Moreover, one or two molecules of EGCG bound to
      double-stranded AG:CT oligomers of various nucleotide lengths. Double-stranded
      DNA (dsDNA) oligomers were detected only as EGCG-bound forms at high temperature,
      whereas at low temperature both the free and bound forms were detected,
      suggesting that EGCG protects double-stranded DNA oligomers from double-stranded
      melting into single-stranded DNA. We assume that catechins accumulate in both
      double-stranded DNA and RNA molecules through multiple administrations of green
      tea beverage in in vivo, and that the accumulated green tea catechins play a
      significant role for human cancer prevention.

PMID- 17440928
TI  - Inhibition of proprotein convertases: approaches to block squamous carcinoma
      development and progression.
AB  - Most proprotein convertase (PC) inhibitors are compounds that act as competitive
      inhibitors. All of them contain the general cleavage motif RXK/RR that binds to
      the PC's active site impairing further interactions with their physiological
      substrates. The first inhibitors synthesized were the acyl-peptidyl-chloromethyl
      ketones that bind to the PC's active site through its peptidyl group and are able
      to transverse the plasma membrane due to the acyl moiety. For instance, one of
      the members of this family that exhibits reduced toxicity and has been widely
      used as an effective general PCs inhbitor is the derivative decanoyl-RVKR
      chloromethylketone (CMK). Another approach to PC inhibition is based on proteins
      that contain either a natural or a bioengineered PC cleavage consensus site. In
      this context, the bioengineered serpin, alpha-1-antitrypsin Portland (alpha 1-PDX
      or PDX), proved to be a potent inhibitor of furin, the most studied of the cancer
      related PCs. Both PDX and CMK were able to inhibit invasiveness of squamous cell
      carcinoma cell lines by blocking activation of cancer-associated PC substrates
      such as MT-MMPs, IGF-1R, and VEGF-C. A similar effect was produced by inhibiting
      PC-mediated processing using furin prosegment. PDX and CMK have also been assayed
      in vivo using skin carcinogenesis models. Newer promising small molecules and RNA
      interference approaches are also being developed to inhibit PCs.

PMID- 17440929
TI  - The role of multiple drug resistance proteins in fetal and/or placental
      protection against teratogen-induced orofacial clefting.
AB  - Previous studies have shown a role for multiple drug resistance proteins in
      protecting the fetus from a limited number of teratogens. We have expanded the
      number of proteins and teratogens examined by comparing the influence of the
      mdr1a and mdr2 proteins on teratogen-induced orofacial clefting using their
      respective knockouts in crosses with the A/J, high susceptibility strain. Western
      blots identified the presence of mdr1a and possibly mdr2 in the placenta and
      fetus. The mdr1a knockout, on its unique genetic background showed lower,
      similar, and higher incidences of clefting compared to A/J for Dilantin,
      hydrocortisone (HC), and 6-aminonicotinamide (6-AN), respectively. The mdr2
      knockout did not affect 6-AN clefting when compared to A/J. In reciprocal
      crosses, when corrected for increased spontaneous clefting, maternally inherited
      A/J susceptibility genes predominated over the effects of the maternal absence of
      mdr1a (with 6-AN). Unlike mdr1a, which had a direct effect in the fetus as shown
      by genotyping of affected versus unaffected fetuses, an effect of mdr2 in the
      fetus was not found. The mdr1a knockout was backcrossed to the A/J inbred strain
      for 11 generations (congenics) to eliminate genetic background effects.
      Reciprocal crosses showed no maternal effect from the lack of mdr1a, confirming
      that mdr1a expression in the fetus, rather than the placenta, protects the fetus
      from teratogens. Mdr2 seems not to be involved in the protection of the fetus
      from teratogens.

PMID- 17440930
TI  - Polymorphisms in the serotonin receptor gene HTR2A are associated with
      quantitative traits in panic disorder.
AB  - Anxiety disorders and specifically panic disorder (PD) are caused by complex
      interactions of environmental and genetic factors. The latter comprise many
      different genes, from which those involved in serotonergic neurotransmission have
      received particular attention. Here we report the results from an association
      candidate-gene approach, where we analyzed 15 single nucleotide polymorphisms
      (SNPs) within the gene coding for the serotonin-receptor 2A (HTR2A) in patients
      suffering from PD and a control sample. We found that the SNP rs2296972 shows an
      association between the number of T-alleles and severity of symptoms in PD. By
      performing tests according to the Fisher product method (FPM), an association
      between HTR2A and the personality trait reward dependence could be shown. Most
      pronounced effects were observable for the SNPs rs2770304, rs6313, and rs6311.
      Furthermore, the polymorphisms rs3742278, rs2296972, and rs2770292 form a
      haplotype, which may be associated with higher susceptibility for PD. These
      results further underline a possible important role of genetic variations within
      the system controlling serotonergic neurotransmission for the development and
      course of disease in PD.

PMID- 17440931
TI  - Obsessive-compulsive symptoms in sibling pairs concordant for obsessive
      compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is a heterogeneous disorder of unknown
      etiology. Phenotypic studies of affected sib-pairs (SPs) may help to characterize
      familial components of the phenotype. To determine whether SPs affected with OCD
      are similar in age at onset of obsessive-compulsive symptoms (OCS), symptom
      dimensions and presence of tic disorders (TDs). Forty OCD siblings ranging from
      13 to 59 years old were evaluated by expert psychiatrists or psychologists.
      Families with two or more siblings affected with OCD were recruited from several
      OCD clinics in Brazil. The Yale Brown Obsessive-Compulsive Scale Checklist was
      used to assess OCS and the severity of OCD. The OCD diagnoses were made according
      to the DSM-IV. The chi-square test was used to assess concordance of TD presence
      within SPs based on the TD frequency reported in the literature (30%). There were
      significantly more siblings with early-onset OCS than with late-onset OCS (P =
      0.002). Age at onset of OCS correlated positively and significantly between the
      two members of each SP (P = 0.005). Fourteen patients (35%) were diagnosed with
      TDs. There was no concordance of the TD presence within the SPs. When both were
      male, there was a significant sibling correlation in the contamination
      obsessions/cleaning compulsions dimension (ICC = 0.74; P = 0.002). Similarly,
      when both siblings were female, they were comparable in the hoarding
      obsessions/compulsions dimension (ICC = 0.76; P = 0.01). Familial factors seem to
      contribute to specific OCD phenotypic components such as age at onset of OCS and
      specific dimensions. The obvious influence of gender is as yet unexplained.

PMID- 17440932
TI  - Anorexia nervosa, perfectionism, and dopamine D4 receptor (DRD4).
AB  - The dopamine D4 receptor (DRD4), a well-characterized, polymorphic gene, is an
      attractive candidate for contributing risk to disordered eating and anorexia
      nervosa (AN). We tested association using UNPHASED for 5 DRD4 polymorphic loci, 3
      promoter region SNPs (C-521T, C-616G, A-809G), the 120 bp promoter region tandem
      duplication and the exon III repeat, in 202 AN trios and 418 control families.
      Since perfectionism characterizes AN, we tested these five loci for association
      with the Child and Adolescent Perfectionism Scale (CAPS) in the AN and control
      groups. Single locus analysis showed significant association between the 'C' C
      521T allele and AN. Haplotype analysis also showed significant association,
      particularly a 4-locus haplotype (exon III&120 bp repeat&C-521T&A-809G).
      Association was also observed between DRD4 and CAPS scores both for AN and
      control subjects. The insulin-like growth factor 2 (IGF2) and the arginine
      vasopressin 1a receptor (AVPR1a), previously shown to be associated with
      disordered eating, were also associated with CAPS scores. Three genes associated
      with AN were also associated with perfectionism. Personality traits are potential
      endophenotypes for understanding the etiology of eating disorders and one of the
      several pathways to eating pathology may be mediated by the impact of DNA
      sequences on perfectionism.

PMID- 17440933
TI  - Interaction between the ADAM12 and SH3MD1 genes may confer susceptibility to late
      onset Alzheimer's disease.
AB  - The neuropathology of Alzheimer's disease (AD) is characterized by intracellular
      neurofibrillary tangles and the extracellular deposition of beta-amyloid (Abeta)
      in senile plaques. Abeta has been shown to mediate neurodegenerative and
      inflammatory changes associated with amyloid plaques, although the pathological
      mechanism of Abeta remains largely unknown. Recent evidence suggests that the
      FISH adapter protein binds to, and potentially regulates, ADAM12 (a disintegrin
      and metalloprotease 12) to mediate a neurotoxic effect of Abeta. The ADAM12 gene
      lies on chromosome 10q26.3, and the gene encoding FISH, SH3MD1, lies within a
      region of linkage to late-onset AD (LOAD) on 10q25.1. This study investigates
      whether there is a relationship between variation in ADAM12 and SH3MD1 and
      susceptibility to LOAD in a sample of 1,051 AD cases and 1,269 matched controls.
      We observe significant interactions between variants in the two genes that may
      influence susceptibility to LOAD. The most significant statistical interaction is
      between rs3740473, a synonymous single nucleotide polymorphism (SNP) in SH3MD1
      and rs11244787, an intronic SNP in ADAM12 (effect size = 2.1 for interaction
      term, P = 0.006).

PMID- 17440934
TI  - Acrodysostosis with unusual iridal color changing with age.
AB  - Acrodysostosis is a rare congenital anomaly syndrome characterized by peculiar
      facial appearance with a small nose and an open mouth, short stature, short
      metacarpotarsal, and phalangeal bones with cone-shaped epiphyses, advanced bone
      age, and variable degrees of mental retardation. It is most likely that the
      disease is inherited in an autosomal dominant mode, its pathogenesis has remained
      unknown. We report a 4-year-old Japanese girl who suffered from acrodysostosis
      with unusual iridal color. The color of patient's irides was gray-bluish in her
      infancy but became light-brownish by age 4 years. Of eight Japanese patients
      reported, four had abnormal eye color: a 7-month-old boy with blue irides and his
      2-year-old elder sister with light-blue eyes a 6-year-old girl with gray-brownish
      irides, and a 4-year-old girl (present case) with blue-brownish irides. The
      degree of iris pigmentation in acrodysostosis patients may change with age. It is
      likely that the putative gene for acrodysostosis might play a role not only in
      remodeling of bones but also in iris pigmentation.

PMID- 17440935
TI  - DAT1 3'-UTR 9R allele: preferential transmission in Indian children with
      attention deficit hyperactivity disorder.
AB  - Genetic alterations in the dopaminergic system are frequently observed in
      association with attention deficit hyperactivity disorder (ADHD) and a 40 bp
      variable number of tandem repeats (VNTR) in the 3'-untranslated region (3'-UTR)
      of the dopamine transporter gene (DAT1) has been investigated in different
      populations. Both significant association and lack of association with the10
      repeat allele (10R) of DAT1 VNTR have been reported. Objective of the present
      investigation was to examine association of this polymorphism with ADHD in Indian
      children. Genotypic data obtained from ADHD probands (n = 79), their parents (n =
      148) and control individuals (n = 153) were analyzed for haplotype-based
      haplotype relative risk analysis (HHRR), transmission disequilibrium test (TDT),
      and family-based association test (FBAT). HHRR analysis revealed significant (P =
      0.009) transmission of shorter alleles (< or =9R). TDT analysis of informative
      ADHD families (n = 32) also exhibited highly significant transmission of the
      shorter alleles (P = 0.002). Further analysis by FBAT showed preferential
      transmission (P = 0.019) of the 9R allele from parents to ADHD probands. It can
      be inferred from the data obtained that the DAT1 3'-UTR 9R allele may confer risk
      of ADHD in the Indian population.

PMID- 17440936
TI  - Association analysis of GABA receptor subunit genes on 5q33 with heroin
      dependence in a Chinese male population.
AB  - GABAA receptor subunit genes clustered on 5q33 play a role in the development of
      alcoholism and methamphetamine use disorder without psychosis. The present study
      explored the possible contribution of the same subunit genes to the development
      of heroin dependence. Single nucleotide polymorphisms (SNPs) of the GABAA
      receptor subunits GABRB2, GABRA6, GABRA1, and GABRG2 were examined in 178 male
      Han Chinese heroin-dependent and 170 male control subjects. A significant
      difference in allele frequency for the SNP rs211014 in the GABAAgamma2 receptor
      subunit gene between cases and controls was identified (P = 0.015). A possible
      mechanism for the involvement of the GABA receptor subunit genes on 5q33 in the
      development of heroin dependence is discussed.

PMID- 17440937
TI  - Neurocognitive deficits in first-episode schizophrenic patients and their first
      degree relatives.
AB  - Some neuropsychological abilities, particularly those affecting memory, attention
      and executive function, are impaired amongst both schizophrenic patients and
      their unaffected relatives, implying that these deficits are at least partly
      genetic in origin. However neuropsychological performance can be altered by
      medication, and has rarely been examined in first onset, drug naive patients. The
      objective of this study was to determine whether selected neurocognitive
      abilities are impaired in first-onset schizophrenic patients and their relatives
      compared to controls. We examined attention and speed of information processing,
      memory and learning, verbal function, visuoconstructive abilities and executive
      function in 207 first-episode schizophrenic patients (163 of whom were drug
      naive), 322 of their first-degree relatives and 133 unrelated normal controls.
      The data were subjected to multilevel modeling to compare neurocognitive
      performance between schizophrenic probands, relatives and controls while taking
      into account potential correlations among members of the same family; age,
      gender, and years of education were included as covariates. Of the three groups,
      schizophrenic patients performed poorest at all neuropsychological tests,
      suggestive of a broad range of neurocognitive deficits. Their first-degree
      relatives showed a narrower pattern of poor performance at Digit Symbol, Digit
      Span, Trail Making, Verbal Fluency test, Tower of Hanoi, and WCST-M tests. Our
      findings show that selected neurocognitive deficits especially attention and
      executive function are impaired in the families of schizophrenic patients. These
      patterns of neurocognitive deficits may represent "endophenotypes" denoting
      varying degrees of vulnerability to schizophrenia and may be of value in future
      molecular genetic studies.

PMID- 17440938
TI  - Late fetal death in offspring and subsequent incidence of prostate cancer in
      fathers: the Jerusalem Perinatal Study cohort.
AB  - BACKGROUND: Little is known of the causes of prostate cancer and few previous
      studies have investigated men's reproductive histories in relation to this
      disease. We sought to determine whether risk of prostate cancer was altered in
      men who had fathered stillborn offspring. METHODS: We studied the incidence of
      prostate cancer (N = 252) in a cohort of 15,268 fathers followed for 28-41 years
      from the birth of a live offspring, whose wives participated in one of two
      separate surveys of outcomes of previous births. Proportional hazards models were
      used to estimate relative risks (RR) associated with previous stillbirths,
      controlling for changes in incidence over time, social and occupational factors.
      RESULTS: The 543 men with one or more stillborn offspring experienced an
      increased risk of prostate cancer (adjusted RR = 1.87, 95% confidence interval =
      1.17-3.00, P = 0.0095), compared to men without stillbirths. With one reported
      stillbirth, the RR was 1.68 (0.99-2.84); with two or more, the RR was 3.29 (1.22
      8.88). Results were consistent in men whose wives were interviewed in 1965-1968
      and 1974-1976. In 100 fathers with no male offspring and at least one stillbirth
      the RR was 4.04 (1.87-8.71, P = 0.0004). CONCLUSIONS: These findings should be
      considered hypothesis-generating and require confirmation in other studies. They
      suggest that stillbirth and prostate cancer may have shared environmental causes;
      alternatively, genetic susceptibility to prostate cancer might increase the risk
      of a stillbirth in offspring.

PMID- 17440939
TI  - Molecular PCA3 diagnostics on prostatic fluid.
AB  - BACKGROUND: The PCA3 test on urine can improve specificity in prostate cancer
      (PCa) diagnosis and could prevent unnecessary prostate biopsies. In this study,
      we evaluated the PCA3 test on prostatic fluid and compared this with the PCA3
      test on urine in a clinical research setting. METHODS: Prostatic fluid and urine
      samples from 67 men were collected following digital rectal examination (DRE).
      The sediments were analyzed using the quantitative APTIMA PCA3 test. The results
      were compared with prostate biopsy results. RESULTS: Using a PCA3 score of 66 as
      a cut-off value, the test on prostatic fluid had 65% sensitivity for the
      detection of PCa, 82% specificity and a negative predictive value of 82%. At a
      cut-off value of 43, the test on urine had 61% sensitivity, 80% specificity and a
      negative predictive value of 80%. CONCLUSIONS: The PCA3 test can be performed on
      both urine and prostatic fluid in the diagnosis of PCa with comparable results.

PMID- 17440940
TI  - Birth of correctly genotyped calves after multiplex marker detection from bovine
      embryo microblade biopsies.
AB  - We report a method for multiplex genotyping of bovine embryo microblade biopsies.
      We have tested the reliability of the method and the viability of the embryos in
      vitro and in vivo. Two polymorphic gene markers (GHR F279Y and PRLR S18N)
      associated with milk production traits and one marker for sex diagnosis (ZFX/ZFY)
      were genotyped simultaneously with a method that combines nested PCR and allelic
      discrimination. To test the accuracy of genotyping, in the first experiment the
      genotypes of 134 biopsies from in vitro produced embryos were compared to
      genotypes determined from the corresponding embryos after biopsy. The method
      proved to be highly accurate as only in three cases (two for PRLR S18N and one
      for GHR F279Y) out of 395 genotypes the genotype was in disagreement between the
      two samples. The viability of similarly biopsied embryos was tested in parallel:
      after 24-hr culture 94.6% of embryos recovered in vitro. In the second
      experiment, a total of 150 in vivo-produced embryos were biopsied on Day 7 and
      genotyped. After the genotyping results were obtained on Day 8, female embryos
      were selected for transfer. From a total of 57 selected embryos 43 were
      transferred individually and 14 as pairs. After single embryo transfers, 19
      recipients became pregnant and after embryo transfers in pairs one became
      pregnant. The success of genotyping was tested with the genotypes of donors and
      bulls and also from the hair samples of born calves. All calves were females and
      of the same genotypes determined from the biopsy.

PMID- 17440941
TI  - DNA methylation and histone acetylation patterns in cultured bovine fibroblasts
      for nuclear transfer.
AB  - Evidence indicates that failure of nuclear transfer (NT) embryos to develop
      normally can be attributed, at least partially, to the use of a differentiated
      cell nucleus as the donor karyoplast. It has been hypothesized that blastocyst
      production and development to term of cloned embryos may differ between
      population doublings (PDs) of the same cell line as a consequence of changes in
      DNA methylation and histone acetylation patterns during in vitro culture. The
      objective of this study was to determine gene expression patterns of the
      chromatin remodeling proteins DNA methyltransferase-1 (Dnmt1), methyl CpG binding
      protein-2 (MeCP2), and histone deacetyltransferse-1 (HDAC1), in addition, to
      measuring levels of DNA methylation and histone acetylation of bovine fibroblast
      cells at different PDs. Bovine fibroblast cell lines were established from four
      50-day fetuses. Relative levels of Dnmt1, MeCP2, HDAC1, methylated DNA, and
      acetylated histone were analyzed at PDs 2, 7, 15, 30, 45, and 70. RNA levels of
      Dnmt1, HDAC1, and MeCP2 were examined using Q-PCR. Global levels of methylated
      DNA and acetylated histone were determined by incubation of fixed cells with an
      anti-5-methylcytidine and anti-acetyl-histone H3 antibody, respectively. Cells
      were labeled with a second antibody, counter-stained with propidium iodide and
      analyzed by flow cytometry. These data demonstrate that chromatin remodeling
      protein mRNAs involved in epigenetic modifications are altered during in vitro
      culture. Methylated DNA and acetylated histone patterns of in vitro cells change
      with time in culture. Subsequent use of these cells for NT will provide insight
      as to how these epigenetic modifications affect reprogramming.

PMID- 17440942
TI  - Understanding comorbidity: a twin study of reading disability and attention
      deficit/hyperactivity disorder.
AB  - A community sample of twins in which at least one member of each pair exhibited
      significant reading difficulties (99 monozygotic and 80 dizygotic pairs) or
      symptoms of attention-deficit/hyperactivity disorder (ADHD; 83 monozygotic and 78
      dizygotic pairs) was used to test the etiology of comorbidity between reading
      disability (RD) and ADHD. Univariate analyses revealed moderate to high
      heritability for all measures of reading difficulty and ADHD. Subsequent
      bivariate analyses indicated that the relation between reading difficulties and
      inattention symptoms is primarily attributable to common genetic influences,
      whereas bivariate heritability estimates were not significant for hyperactivity
      impulsivity and any of the reading measures. Reading difficulties and ADHD
      symptoms were more highly heritable if the proband met criteria for both
      disorders versus RD or ADHD alone, suggesting that future molecular genetic
      analyses of comorbid RD + ADHD may facilitate the identification of
      susceptibility genes for RD, ADHD, and their comorbidity.

PMID- 17440943
TI  - Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with
      plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk.
AB  - BACKGROUND: The vitamin D receptor (VDR) is required for actions of vitamin D.
      The binding of 1,25-dihydroxyvitamin D to the VDR on prostatic epithelial cells
      prompts the regulation of cancer-related genes. METHODS: We conducted a nested
      case-control study in the Health Professionals Follow-up Study to investigate the
      role of the VDR Cdx2, Fok1, and Bsm1 gene polymorphisms and associated haplotypes
      and their interaction with plasma vitamin D metabolites in relation to prostate
      cancer (PC) risk. RESULTS: No association was found between these SNPs or their
      associated haplotypes and all PC subtypes except that haplotype 2 (A-f-b) with
      Cdx2 A, Fok1 f, and Bsm1 b alleles and haplotype 3 (A-F-B) with Cdx2 A, Fok1 F
      and Bsm1 B alleles compared to the most common haplotype (A-F-b), were associated
      with reduced risk of aggressive PC (high stage or Gleason sum > or =7; P = 0.02),
      both with two alleles suspected of being low risk. Carriers of the variant Cdx2 A
      allele who were deficient in plasma 25-hydroxyvitamin D (< or =15 ng/ml) compared
      to non-carriers with normal 25-hydroxyvitamin D, had a lower risk of total and
      poorly differentiated PCs (Gleason sum > or =7) (P for interaction = 0.02 and
      0.04, respectively). Plasma 1,25-dihydroxyvitamin D deficiency (< or =26 pg/ml)
      was associated with a threefold risk of poorly differentiated PC (P for
      interaction = 0.01) when comparing carriers of the Cdx2 A allele to non-carriers
      with normal 1,25-dihydroxyvitamin D. CONCLUSION: In this population of men, none
      of the VDR polymorphisms studied was associated with susceptibility to PC.

PMID- 17440944
TI  - ErbB-4 may control behavior of prostate cancer cells and serve as a target for
      molecular therapy.
AB  - PURPOSE: To assess ErbB-4 expression in advanced human prostate cancer (PC) cell
      lines, the role of ErbB-4 in motility, migration, and proliferative/tumorigenic
      potential of PC cells, and efficacy of anti-ErbB-4 monoclonal antibody (Mab)
      treatment on PC cells in vitro and tumor growth in vivo. MATERIALS AND METHODS:
      Established advanced human PC cell lines (PC-3, Cl-1, and Du-145) were evaluated
      for ErbB-4 expression. Several Cl-1 cell line clones expressing various levels of
      ErbB-4 were isolated, their motility, migration capacity, and in vitro
      proliferation as well as survival following Mab treatment were evaluated.
      Tumorigenicity and proliferation capacity of these clones in vivo and efficacy of
      Mab treatment on tumor growth were estimated by measurements of subcutaneous
      tumors developed in nude mice. RESULTS: PC cell lines studied express ErbB-4.
      Both PC-3 and Du-145 cell lines express high ErbB-4 levels; only 50% of Cl-1
      cells express ErbB-4 with large heterogeneity. Cl-1 sub-clones highly expressing
      ErbB-4 showed increased cell motility, migration, and proliferation rate in vitro
      and enhanced growth in vivo, compared to clones with low ErbB-4 expression. Mab
      treatment inhibited the growth of cells expressing high but not low ErbB-4 levels
      in vitro and decreased the growth of subcutaneous tumors in nude mice generated
      by ErbB-4 highly expressing cells. CONCLUSIONS: High expression of ErbB-4 in
      prostate cancer Cl-1 cell clones correlated with high proliferative and migration
      capacity and high tumorigenic potential. The inhibitory effect of Mab on cell
      proliferation and on subcutaneous tumor growth suggests ErbB-4's potential as a
      target for molecular anticancer therapy.

PMID- 17440945
TI  - Correlations between the Psychological Inventory of Criminal Thinking Styles and
      World-View Rating Scale in male federal prisoners.
AB  - INTRODUCTION: The lifestyle theory of criminal behaviour maintains that criminal
      thinking is hierarchically organized and that certain features of an individual's
      general world view should correspond with specific criminal thinking styles.
      HYPOTHESES: It was predicted that the eight Psychological Inventory of Criminal
      Thinking Styles (PICTS) thinking style scales would correlate with the mechanism,
      fatalism, inequity and malevolence poles of the four World-View Rating Scale
      (WVRS) dimensions. METHOD: A group of 140 male medium security prison inmates
      rated themselves on the four dimensions of the WVRS and completed the PICTS.
      RESULTS: All eight PICTS thinking style scales correlated with mechanism,
      inequity and malevolence, but only six of the eight PICTS scales correlated with
      fatalism. In addition, two of four correlations specified a priori (i.e. between
      mollification and inequity and between power orientation and malevolence) proved
      significant in this study. DISCUSSION: The present findings suggest that two
      levels of a cognitive system held to be instrumental in maintaining a criminal
      lifestyle - criminal thinking styles and global belief systems - may be
      meaningfully linked.

PMID- 17440946
TI  - Self-regulation in violent and non-violent offenders: a preliminary report.
AB  - BACKGROUND: The functional role of self-regulation in violent behaviour is not
      yet fully understood. AIM: To test the hypothesis that violent offenders have
      more deficits in self-regulation and self-control than non-violent offenders.
      METHODS: Self-regulation and personality disorders were evaluated in a sample of
      70 violent and non-violent incarcerated offenders using the Volitional Components
      Questionnaire (VCQ) and the SCID-II for DSM-IV. RESULTS: The self-report data
      indicate that violent offenders were no different from non-violent offenders on
      either facilitatory or inhibitory modes of self-regulation and self-control.
      Compared with a sample of normal, healthy men, differences were found in all
      tested self-regulation variables but not in self-control. Except for antisocial
      personality, the groups were similar in personality features. CONCLUSIONS: The
      proposed hypothesis was not sustained on this measure of self-regulation. With
      regard to self-regulation and self-control, violent and non-violent offenders
      were similar and treatment interventions to improve capacity in these respects
      are probably useful for both groups.

PMID- 17440947
TI  - Lack of mutations in spinocerebellar ataxia type 2 and 3 genes in a Taiwanese
      (ethnic Chinese) cohort of familial and early-onset parkinsonism.
AB  - Recent reports suggest that CAG triplet expansions of spinocerebellar ataxia type
      2 and 3 (SCA2 and SCA3) genes are the cause of typical levodopa-responsive
      Parkinson's disease (PD) in familial cases, several of which were ethnic Chinese.
      To investigate the role of SCA2 and SCA3 mutations in Chinese familial and early
      onset PD patients, we analyzed CAG triplet repeat expansions of SCA2 and SCA3
      genes in a cohort of 73 Taiwanese/Ethnic Chinese familial and early-onset PD
      patients [mean age at onset 42.70 +/- 7.17 years (mean +/- SD)]. Thirteen of them
      (17.8%) had positive family history. All patients received comprehensive clinical
      evaluation including a thorough neurological examination, laboratory tests, and
      neuroimaging studies to exclude secondary causes and atypical parkinsonism. The
      CAG repeat length in these genes was determined using polymerase chain reaction
      polyacrylamide gel electrophoresis. SCA2 gene CAG repeats ranged from 15 to 26
      repeats with a median of 20, and SCA3 gene CAG repeats ranged from 15 to 40 with
      a median of 15. No long pathogenic repeats were found in either SCA2 or SCA3,
      although borderline CAG repeat number was detected in the SCA3 gene of four
      patients. Thus, mutations of SCA2 or SCA3 did not play a major role in familial
      or early-onset PD in our study cohort. PD patients without autosomal dominant
      family history or obvious cerebellar ataxia should not be candidates for routine
      screening of SCA2 or SCA3 mutations for cost-effectiveness.

PMID- 17440948
TI  - Candidate gene association study of insulin signaling genes and Alzheimer's
      disease: evidence for SOS2, PCK1, and PPARgamma as susceptibility loci.
AB  - Epidemiological evidence supports the existence of a possible link between type
      II diabetes mellitus (T2DM) and late-onset Alzheimer's disease (LOAD).
      Polymorphisms from candidate genes for T2DM were genotyped in a two-stage
      approach to identify novel risk factors for LOAD. One hundred fifty-two
      polymorphisms were initially genotyped in a case:control cohort: nine SNPs showed
      individual association with disease status under at least one genetic model,
      while an additional two SNPs showed a haplotype association. In a replication
      study, we confirmed significant association of SNPs within three genes-
      PPARgamma, SOS2, and PCK1--with Alzheimer's disease. In particular, our data
      suggest that the effect of variants within these genes might be influenced by
      gender.

PMID- 17440949
TI  - Mitochondrial DNA haplogroups and age at onset of schizophrenia.
AB  - A number of studies support a possible link between mitochondrial dysfunction and
      schizophrenia. To test the hypothesis of a direct contribution of mitochondrial
      DNA (mt-DNA) in susceptibility to DSM-IV-TR-schizophrenia, we looked for
      differences in the frequency distribution of the major European haplogroups (hgs)
      in 142 patients and 190 controls both of Italian origin. A subgroup of patients
      (N = 37) and healthy counterparts (N = 41) was also analyzed for possible
      differences in the relative amount of mt-DNA versus nuclear-DNA in blood cells.
      Patients and controls were comparable for hg frequency distribution and the
      relative levels of mt-DNA even after stratification by gender and schizophrenia
      subtype. However, patients harboring the hg J-T showed an anticipated onset of
      the disorder. These results indicate that the J-T hg of mt-DNA may have a
      modulator effect on deeper determinants of schizophrenia.

PMID- 17440950
TI  - Immunohistochemical staining for mismatch repair proteins, and its relevance in
      the diagnosis of hereditary non-polyposis colorectal cancer.
AB  - BACKGROUND: Hereditary non-polyposis colorectal cancer (HNPCC) arises mostly from
      germline mutations of the mismatch repair genes MSH2 and MLH1. The diagnosis of
      HNPCC is based on a set of clinical criteria that may be too restrictive to
      identify all affected patients. Immunohistochemical staining (IHC) for the
      mismatch repair proteins, MutS homologue 2 (MSH2) and MutL homologue 1 (MLH1),
      reliably identifies the microsatellite instability phenotype. This study
      evaluated the ability of IHC to detect germline mutations in an unselected group
      of patients with colorectal cancer (CRC). METHODS: All patients with CRC operated
      on between July 2000 and March 2003, and demonstrating a loss of protein, were
      contacted. Following informed consent, searchs for germline mutation and
      methylation of the promoter were performed on normal and tumoral DNA. RESULTS:
      Thirty patients agreed to participate, four of whom fulfilled the Amsterdam II
      criteria. Loss of expression of MLH1 was found in 20 patients, and loss of
      expression of MSH2 in ten patients. Four of the MLH1-deficient patients had a
      germline MLH1 point mutation (positive predictive value (PPV) 20 (95 per cent
      confidence interval (c.i.) 2 to 38 per cent) and 11 had promoter methylation.
      Seven of the MSH2-deficient patients had a germline MSH2 point mutation (PPV 70
      (95 per cent c.i. 54 to 96 per cent), and none showed promoter methylation.
      CONCLUSION: MLH1-deficient patients who are young or have a positive family
      history of cancer should be referred for genetic testing and counselling, whereas
      MSH2-deficient patients should be counselled in the same way as patients with
      HNPCC.

PMID- 17440951
TI  - Gene-lifecourse interaction for alcohol consumption in adolescence and young
      adulthood: five monoamine genes.
AB  - Association analysis has suggested that common sequence variants of genes that
      affect monoamine function can affect substance use and abuse. Demonstration of
      these associations has been inconsistent because of limited sample sizes and
      phenotype definition. Drawing on the life course perspective, we predicted a
      stronger association between the polymorphisms in 5HTT, DAT1, DRD4, DRD2, and
      MAOA and alcohol consumption in young adulthood than adolescence. This analysis
      tested for the gene-lifecourse interaction for the frequency of alcohol
      consumption in a nationally representative non-alcohol-dependent sample of 2,466
      individuals that were visited during adolescence and young adulthood for four
      times between 1994 and 2002. All five genes are significantly associated with the
      frequency of alcohol consumption, with the genotype effects ranging 7%-20% of the
      mean score of alcohol consumption and their P values being 0.014, 0.0003, 0.003,
      0.007, 0.005, and 0.003, respectively. The association is only observed in the
      life stage of young adulthood and not in adolescence. This analysis has
      demonstrated the potential usefulness of the life course perspective in genetic
      studies of human behaviors such as alcohol consumption.

PMID- 17440952
TI  - Immunological evaluation of neoadjuvant peptide vaccination before radical
      prostatectomy for patients with localized prostate cancer.
AB  - BACKGROUND: The purpose of this study was to determine the safety and immune
      responses of pre-operative personalized peptide vaccine for patients with
      localized prostate cancer. METHOD: Ten human leukocyte antigen (HLA)-A24(+)
      patients with localized prostate cancer received weekly personalized peptide
      vaccine for six times with positive peptides (up to four kinds of peptides) from
      16 kinds of vaccine candidates, followed by a retropubic radical prostatectomy
      (RRP). Eight patients with localized prostate cancer receiving RRP served as the
      control group. The serum prostate-specific antigen (PSA) level, and peptide
      specific cytotoxic T lymphocyte (CTL) precursor analysis by interferon-gamma
      production, and peptide-reactive immunoglobulin G (IgG) using an enzyme-linked
      immunosorbent assay were monitored during the treatment. Distributions of
      CD45RO(+) cells, CD8(+) T cells, and CD20(+) B cells in tissue microarray samples
      were studied using an immunohistochemical technique. RESULT: The peptide
      vaccination was safe and well tolerated with no major adverse effects. Increased
      CTL response and the anti-peptide IgG titer were observed in the post-vaccination
      samples in 8 of 10 or 8 of 10 patients, respectively. The intensity of CD45RO(+)
      infiltrating cells in the vaccination group was significantly larger than that in
      the control group. CD8(+) T cell infiltration was seen only in the vaccinated
      group. CONCLUSION: Increased immune responses, at both the circulation and tumor
      sites in the vaccinated group, support the further development of personalized
      peptide vaccines for patients with localized prostate cancer.

PMID- 17440953
TI  - Neuroimaging endophenotypes: strategies for finding genes influencing brain
      structure and function.
AB  - It is vitally important to identify the genetic determinants of complex brain
      related disorders such as autism, dementia, mood disorders, and schizophrenia.
      However, the search for genes predisposing individuals to these illnesses has
      been hampered by their genetic and phenotypic complexity and by reliance upon
      phenomenologically based qualitative diagnostic systems. Neuroimaging
      endophenotypes are quantitative indicators of brain structure or function that
      index genetic liability for an illness. These indices will significantly improve
      gene discovery and help us to understand the functional consequences of specific
      genes at the level of systems neuroscience. Here, we review the feasibility of
      using neuroanatomic and neuropsychological measures as endophenotypes for brain
      related disorders. Specifically, we examine specific indices of brain structure
      or function that are genetically influenced and associated with neurological and
      psychiatric illness. In addition, we review genetic approaches that capitalize on
      the use of quantitative traits, including those derived from brain images.

PMID- 17440954
TI  - Ultrastructure of the protonephridial system in Neodasys chaetonotoideus
      (Gastrotricha: Chaetonotida) and in the ground pattern of Gastrotricha.
AB  - The taxon Neodasys has a basal position within Gastrotricha. This makes it very
      interesting for phylogenetic considerations in this group. To complete the
      reconstruction of the nephridial system in the stem species of Gastrotricha
      started earlier, we have studied the whole protonephridial system of Neodasys
      chaetonotoideus by means of complete sets of ultrathin sections and TEM. In many
      characters, protonephridia of N. chaetonotoideus resemble those of macrodasyidan
      gastrotrich species. For example, each of the six protonephridia, arranged in
      three pairs, consists of three distinct cells that constitute the continuous
      protonephridial lumen. Especially, the terminal cell of the protonephridia of N.
      chaetonotoideus shows a striking pattern: The perforation of the filter region is
      a meandering cleft that is continuous with the seam of the enfolded lumen of that
      cell. With the results presented here and that of former TEM studies, we give a
      comprehensive idea of the excretory organs in the ground pattern of Gastrotricha.
      Moreover, we can elaborate on the hypothesized protonephridial system in the stem
      species of Bilateria. We suggest that a meandering filtration cleft is a feature
      of the ground pattern of the Bilateria.

PMID- 17440955
TI  - Risk of invasion and axillary lymph node metastasis in ductal carcinoma in situ
      diagnosed by core-needle biopsy.
AB  - BACKGROUND: The aim of the study was to assess the risk of invasion and axillary
      lymph node metastasis in patients with ductal carcinoma in situ (DCIS) diagnosed
      by preoperative core-needle biopsy. The data were used to select criteria for
      patients in whom sentinel node (SN) biopsy might be indicated. METHODS: One
      hundred and seventy-one women with 172 DCIS lesions diagnosed by core-needle
      biopsy were analysed. Axillary staging was performed by SN biopsy, axillary node
      sampling, or level 1-2 axillary lymph node dissection. RESULTS: Invasive breast
      cancer was found in the surgical specimens from 45 tumours (26.2 per cent). Risk
      factors for invasion were a palpable lesion (odds ratio (OR) 2.95 (95 per cent
      confidence interval 1.20 to 7.26); P = 0.019), presence of a mass on mammography
      (OR 3.06 (1.43 to 6.56); P = 0.004), and intermediate (OR 5.81 (1.18 to 28.57); P
      = 0.030) or poorly differentiated (OR 5.46 (1.17 to 25.64); P = 0.031) tumour
      grade. Lymph node metastases were found in ten women with DCIS and invasion on
      final pathology. Factors associated with metastases were age 55 years or less (P
      = 0.030), invasion of 1.0 cm or more (P < 0.001) and the presence of vascular
      invasion (P = 0.001). CONCLUSION: SN biopsy should be considered in women with an
      initial diagnosis of DCIS on core-needle biopsy who are at risk for invasion;
      this includes women with a palpable lump, a mass on mammography, and intermediate
      or poor tumour grade.

PMID- 17440956
TI  - Mid-term survival after abdominal aortic aneurysm surgery predicted by
      cardiopulmonary exercise testing.
AB  - BACKGROUND: Cardiopulmonary exercise (CPX) testing measures how efficiently
      subjects meet increased metabolic demand. This study aimed to determine whether
      preoperative CPX testing predicted postoperative survival following elective
      abdominal aortic aneurysm (AAA) repair. METHODS: Some 130 patients had CPX
      testing before elective open AAA repair. Additional preoperative, operative and
      postoperative variables were recorded prospectively. Median follow-up was 35
      months. The correlation of variables with survival was assessed by single and
      multiple regression analyses. RESULTS: CPX testing identified 30 of 130 patients
      who had been unfit before surgery. Two years after surgery the Kaplan-Meier
      survival estimate was 55 per cent for the 30 unfit patients, compared with 97 per
      cent for the 100 fit patients. The absolute difference in survival between these
      two groups at 2 years was 42 (95 per cent confidence interval 18 to 65) per cent
      (P < 0.001). CONCLUSION: Preoperative CPX testing, combined with simple co
      morbidity scoring, identified patients unlikely to survive in the mid-term, even
      after successful AAA repair.

PMID- 17440957
TI  - High preoperative prevalence of deep venous thrombosis in patients with
      colorectal cancer.
AB  - BACKGROUND: Deep venous thrombosis (DVT) is a major complication of cancer and a
      predictor of reduced survival. The postoperative prevalence of DVT in colorectal
      cancer surgery is high, but the preoperative prevalence is unknown. The aim of
      this observational study was to estimate the preoperative prevalence of DVT in
      patients with colorectal cancer. METHODS: Some 193 consecutive patients with
      newly diagnosed colorectal cancer admitted for intended curative surgery were
      examined with compression ultrasonography for DVT before surgery. RESULTS: DVT
      was detected in 15 (7.8 per cent) of the 193 patients, with a prevalence of 16
      per cent in women (12 of 76) versus 2.6 per cent in men (three of 117 (adjusted
      odds ratio (OR) 5.8 (95 per cent confidence interval (c.i.) 1.4 to 23.2)). The
      risk of DVT was strongly correlated with increasing American Society of
      Anesthesiologists (ASA) risk score: adjusted OR 6.8 (95 per cent c.i. 1.6 to 28.7
      for ASA group III or IV versus ASA group I or II). Pulmonary embolism was
      detected in two patients (1.0 per cent). CONCLUSION: A high preoperative
      prevalence of DVT was observed in patients with colorectal cancer, especially
      among women and patients in ASA groups III and IV.

PMID- 17440958
TI  - Identification of genetic networks involved in the cell growth arrest and
      differentiation of a rat astrocyte cell line RCG-12.
AB  - The purpose of the present study is to establish and characterize a conditionally
      immortalized astrocyte cell line and to clarify the genetic networks responsible
      for the cell growth arrest and differentiation. A conditionally immortalized
      astrocyte cell line, RCG-12, was established by infecting primary cultured rat
      cortical glia cells with a temperature-sensitive simian virus 40 large T-antigen.
      At a permissive temperature of 33 degrees C, the large T-antigen was expressed
      and cells grew continuously. On the other hand, the down-regulation of T-antigen
      at a non-permissive temperature of 39 degrees C led to growth arrest and
      differentiation. The cells expressed astrocyte-expressed genes such as glial
      fibrillary acidic protein. Interestingly, the differentiated condition induced by
      the non-permissive temperature significantly elevated the expression levels of
      several astrocyte-expressed genes. To identify the detailed mechanisms by which
      non-permissive temperature-induced cell growth arrest and differentiation, we
      performed high-density oligonucleotide microarray analysis and found that 556 out
      of 15,923 probe sets were differentially expressed 2.0-fold. A computational gene
      network analysis revealed that a genetic network containing up-regulated genes
      such as RB, NOTCH1, and CDKN1A was associated with the cellular growth and
      proliferation, and that a genetic network containing down-regulated genes such as
      MYC, CCNB1, and IGF1 was associated with the cell cycle. The established cell
      line RCG-12 retains some characteristics of astrocytes and should provide an
      excellent model for studies of astrocyte biology. The present results will also
      provide a basis for understanding the detailed molecular mechanisms of the growth
      arrest and differentiation of astrocytes.

PMID- 17440959
TI  - Functional three-dimensional HepG2 aggregate cultures generated from an
      ultrasound trap: comparison with HepG2 spheroids.
AB  - Three-dimensional culture systems are an ideal in vitro model being capable of
      sustaining cell functionalities in a manner that resembles the in vivo
      conditions. In the present study, we developed an ultrasound trap-based technique
      to rapidly produce HepG2 hepatocarcinoma cell aggregates within 30 min. Enhanced
      junctional F-actin was observed at the points of cell-cell contact throughout the
      aggregates. HepG2 aggregates prepared by the ultrasound trap can be maintained in
      culture on a P-HEMA-coated surface for up to 3 weeks. The cells in these
      aggregates proliferated during the initial 3 days and cell number was consistent
      during the following maintenance period. Albumin secretion from these HepG2
      aggregates recovered after 3 days of aggregate formation and remained relatively
      stable for the following 12 days. Cytochrome P450-1A1 activity was significantly
      enhanced after 6 days with maximal enzyme activity observed between 9 and 18
      days. In addition, comparison experiments demonstrated that HepG2 aggregates
      generated by the ultrasound trap had comparable functional characterizations with
      HepG2 spheroids formed by a traditional gyrotatory-mediated method. Our results
      suggest that HepG2 aggregate cultures prepared through the ultrasound trap-based
      technique may provide a novel approach to produce in vitro models for hepatocyte
      functional studies.

PMID- 17440960
TI  - The murine ortholog of the SHP-2 binding molecule, PZR accelerates cell migration
      on fibronectin and is expressed in early embryo formation.
AB  - The human P zero-related protein (hPZR) has a unique function in regulating cell
      migration. This activity is dependent on both its cytoplasmic immunoreceptor
      tyrosine inhibitory motif (ITIM) and its interaction with the tyrosine protein
      phosphatase, src homology phosphatase-2 (SHP-2). Here, using in silico and cDNA
      cloning approaches, we identify the murine ITIM-containing hPZR ortholog, mPZR,
      together with its ITIM-less isoform, mPZRb. We demonstrate that, like hPZR, these
      type 1 integral murine transmembrane isoforms are derived by differential
      splicing from a single gene transcription unit on mouse chromosome 1, and differ
      only in the sequence of their cytoplasmic domains. Importantly, mPZR mimicks hPZR
      functionally by accelerating SHP-2-mediated cell migration on fibronectin.
      Interestingly, we further demonstrate that although neither mPZR nor mPZRb is
      expressed in murine pluripotent embryonic stem cells, they first appear at
      approximately day 3 of blastocyst formation in vivo and of embryoid body
      formation in vitro. These studies thus provide the basis for defining the
      function of the mPZR isoforms in vivo, particularly with respect to their roles
      in regulating SHP-2-dependent cell migration during development.

PMID- 17440961
TI  - Disruption of FRNK expression by gene targeting of the intronic promoter within
      the focal adhesion kinase gene.
AB  - FRNK, a non-catalytic variant of focal adhesion kinase (FAK), is expressed in
      major blood vessels throughout mouse development and is postulated to play a role
      in regulating cell adhesion and signaling in vascular smooth muscle cells
      (VSMCs). The FRNK transcriptional start site lies within an intron of the FAK
      gene, suggesting that the FRNK gene is a "gene within a gene". Here, we
      identified a 1 kb intronic sequence of the FAK gene that is necessary for
      endogenous FRNK expression. Deletion of this sequence in gene-targeted mice
      abolished FRNK expression, showing the direct involvement of the FAK intron in
      the regulation of FRNK expression. The level of FAK expression was normal in the
      FRNK-deficient mice, indicating that FAK and FRNK are transcriptionally regulated
      by distinct promoters. The FRNK-deficient mice were viable, fertile, and
      displayed no obvious histological abnormalities in any of the major blood
      vessels. Western blot analysis showed that FRNK-deficient and wild-type (WT)
      cells had comparable levels of steady-state and adhesion-dependent FAK
      autophosphorylation. Despite the fact that ectopic expression of FRNK suppresses
      focal adhesion formation in cultured cells, these results suggest that endogenous
      FRNK is not essential for development or the formation of the mouse vasculature.

PMID- 17440962
TI  - Expression of alphaV and beta3 integrin subunits during implantation in pig.
AB  - Integrin are adhesion molecules involved in uterine-conceptus interactions during
      the perimplantation period. In this study, the expression of alphaV and beta3
      integrin subunits in endometrium during implantation in pigs was investigated.
      The immunohistochemical location was performed on paraformaldehyde-fixed,
      paraffin-embedded tissue sections, and the mRNA expression of alphaV was detected
      in endometrium. In addition, serum levels of estradiol, progesterone, follicle
      stimulating hormone, and luteinizing hormone were measured on Days 0, 12, 18, and
      25 of pregnancy. The results indicate that endometrium expressed integrin alphaV
      and beta3 in all stages examined. The most intensive staining for integrin alphaV
      and beta3 was observed in endometrial stroma in porcine pregnancy on Day 18. The
      mRNA of alphaV integrin strongly expressed on Day 18, and moderately expressed on
      Days 12 and 25. The correlation between serum hormone level and the mRNA
      expression of alphaV integrin was not significant. The expression patterns of
      integrin alphaV and beta3 during implantation provide insights into the important
      physiological function of alphaVbeta3 integrin in pig, and the strong expression
      of integrin alphaV and beta3 in mid-implantation may indicate its crucial role in
      successful implantation and embryo survival.

PMID- 17440963
TI  - The establishment of two paclitaxel-resistant prostate cancer cell lines and the
      mechanisms of paclitaxel resistance with two cell lines.
AB  - BACKGROUND: Although paclitaxel is used for hormone-resistant prostate cancer,
      relapse definitely occurs later. Details of the molecular mechanism responsible
      for paclitaxel- resistance remain unclear. METHODS: We established paclitaxel
      resistant cells, DU145-TxR and PC-3-TxR from parent DU145 and PC-3. To
      characterize these cells, we examined cross-resistance to other anticancer drugs.
      Expression of several potential genes that had been related to drug-resistance
      was compared with parent cells by RT-PCR and Western blotting. Methylation
      analysis of multiple drug resistance (MDR1) promoter was carried out using
      bisulfite-modified DNA from cell lines. Knockdown experiments using small
      interfering RNA (siRNA) were also performed to confirm responsibility of drug
      resistance. Finally, cDNA microarray was performed to quantify gene expression in
      PC-3 and PC-3-TxR cells. RESULTS: The IC(50) for paclitaxel in DU145-TxR and PC-3
      TxR was 34.0- and 43.4-fold higher than that in both parent cells, respectively.
      Both cells showed cross-resistance to some drugs, but not to VP-16 and cisplatin.
      Methylation analysis revealed that methylated CpG sites of MDR1 promoter in DU145
      and PC-3 cells were demethylated in DU145-TxR cells, but not in PC-3-TxR cells.
      Knockdown of P-glycoprotein (P-gp), which was up-regulated in resistant cells, by
      MDR-1 siRNA restored paclitaxel sensitivity in DU145-TxR but not in PC-3-TxR,
      indicating that up-regulation of P-gp was not always main cause of paclitaxel
      resistance. Microarray analysis identified 201 (1.34%) up-regulated genes and 218
      (1.45%) out of screened genes in PC-3-TxR. CONCLUSIONS: Our data will provide
      molecular mechanisms of paclitaxel-resistance and be useful for screening target
      genes to diagnose paclitaxel sensitivity.

PMID- 17440964
TI  - Regulation of prostate cancer cell growth and PSA expression by angiotensin II
      receptor blocker with peroxisome proliferator-activated receptor gamma ligand
      like action.
AB  - BACKGROUND: We previously reported that angiotensin II (AII) activated the
      proliferation of prostate cancer cells, and its antagonist, an AII receptor type
      1 (AT1R) blocker (ARB), inhibited the proliferation of prostate cancer in vitro
      and in vivo. In the present study, we investigated whether telmisartan, an ARB,
      has a unique feature as a peroxisome proliferator-activated receptor gamma
      (PPARgamma) ligand, and its suppressive potential on prostate cancer cells.
      METHODS: Cell count or MTT assay were carried out for growth suppression of
      prostate cancer cells. Phosphorylation of mitogen-activated protein kinase
      (MAPK), specific expression of prostate specific antigen (PSA) and AT1R were
      investigated by western blot. To confirm the PPARgamma activity of ARBs,
      luciferase assay using PSA promoter and PPARgamma response elements (PPRE)
      plasmids was performed. RESULTS: The results showed that cell proliferation and
      signal transduction were inhibited by telmisartan treatment. Also, inhibition of
      PSA expression by telmisartan was confirmed by western blot and luciferase assay,
      indicating that an ARB acted in a similar way such as an anti-androgenic agent in
      prostate cancer cells. CONCLUSION: The present study showed ARBs, especially
      those possessing a PPARgamma ligand-like structure, have a potential antagonistic
      effect on androgen-dependent and -independent prostate cancer.

PMID- 17440965
TI  - Superovulatory response to a low dose single-daily treatment of rhFSH dissolved
      in polyvinylpyrrolidone in rhesus monkeys.
AB  - To simplify the procedure for superovulation in the rhesus monkey, this study was
      designed using polyvinylpyrrolidone (PVP) solution as a solvent for
      gonadotropins. Thirty-five cycling females (aged 5-8 years old) were divided into
      six groups during the breeding season (November- February). The groups were as
      follows: Group I, animals received twice-daily 35 IU recombinant human follicle
      stimulating hormone (rhFSH) dissolved in 0.5 ml saline for 8 days as the control;
      Groups II and III, animals received single-daily 35 IU and 17 IU rhFSH in 0.5
      saline, respectively, for 9 days; Groups IV, V and VI, received single-daily
      injection of 35 IU rhFSH, 17 IU rhFSH and 8.5 IU rhFSH dissolved in 0.5 ml 30%
      PVP (w/v) solution, respectively, for 9 days. After human chorionic gonadotropin
      was administered to induce the nuclear maturation of oocytes, oocytes were
      retrieved and the development competence of recovered oocytes treated with in
      vitro fertilization were observed. The plasma concentrations of follicle
      stimulating hormone and ovarian responses were monitored during the treatment.
      The results showed that the number of recovered oocytes and the in vitro
      developmental competence of mature oocytes was equivalent among monkeys when
      treated with a single-daily treatment of 17 and 35 IU rhFSH with PVP preparation
      in Groups IV and V compared with the twice-daily 35 IU rhFSH treatments received
      by Group I. However, almost all animals in Groups II, III and VI responded poorly
      to corresponding stimulations. These findings indicate that a single-daily low
      dose of rhFSH dissolved in PVP solution can induce the satisfactory ovarian
      responses in rhesus monkeys. This has the potential to reduce treatment distress,
      stress to the animals, the labor of the operator as well as the amount of rhFSH
      used in ovarian stimulation, compared with traditional superovulation methods.

PMID- 17440966
TI  - Lithium suppresses cell proliferation by interrupting E2F-DNA interaction and
      subsequently reducing S-phase gene expression in prostate cancer.
AB  - BACKGROUND: Lithium is an existing drug for bipolar disorder and its uptake was
      recently linked to reduced tumor incidence compared to the general population.
      The major target of lithium action is glycogen synthase kinase 3 (GSK-3). Since
      GSK-3 expression and activation are associated with prostate cancer progression,
      the anti-cancer potential of lithium on prostate cancer was investigated in this
      study. METHODS: Multiple prostate cancer cell lines were treated with lithium
      chloride (LiCl). Cell proliferation and cell cycle distribution were analysed.
      DNA replication was determined using BrdU labeling assay. Genome-wide screening
      of gene expression was performed using cDNA microarray assay. GSK-3beta gene
      specific silencing was conducted using small interferencing RNA (siRNA)
      transfection. E2 factor (E2F) transactivation was evaluated using reporter gene
      assay and E2F-DNA interaction was determined with chromatin-immunoprecipitation
      assay (ChIP). RESULTS: LiCl significantly inhibited cell proliferation, which was
      associated with reduced DNA replication and S-phase cell cycle arrest. LiCl
      significantly decreased the expression of multiple DNA replication-related genes,
      including cell division cycle 6 (cdc6), cyclin A, cyclin E, and cdc25C, which are
      regulated by E2F factor during cell cycle. A novel GSK-3-specific inhibitor TDZD
      8 and GSK-3beta siRNA also suppressed the expression of these E2F target genes,
      indicating that LiCl-induced anti-cancer effect was associated with GSK-3beta
      inhibition. Furthermore, LiCl suppressed E2F transactivation by interrupting the
      interaction of E2F1 factor with its target gene promoter. CONCLUSIONS: These data
      indicated that LiCl suppresses cancer cell proliferation by disrupting E2F-DNA
      interaction and subsequent E2F-mediated gene expression in prostate cancer.

PMID- 17440967
TI  - The bisphosphonate YM529 inhibits osteoblastic bone tumor proliferation of
      prostate cancer.
AB  - BACKGROUND: In men, prostate cancer frequently metastasizes to the bones, where
      it forms osteoblastic lesions with an osteolytic element that cause pain.
      However, the role of osteoclastogenesis in bone metastasis of human prostate
      cancer is unknown. Bisphosphonates are already known to be beneficical for
      treating osteolytic bone metastases, so we employed a model of osteoblastic bone
      tumor of human prostate cancer to investigate whether a new bisphosphonate
      (YM529: minodronate) could inhibit both the formation of bone tumors and the
      progression of established osteoblastic tumors. METHODS: Human prostate cancer
      cells (LNCaP) were injected into adult human bone implants in nonobese
      diabetic/severe combined immunodeficient mice, after which osteoblastic bone
      tumors developed. YM529 (1 microg/day) was administered subcutaneously every day
      for 2 weeks, starting either immediately or 2 weeks after implantation of the
      tumor cells, and the mice were sacrificed at 4 weeks after implantation. The bone
      tumors were examined histologically and the number of tartrate-resistant acid
      phosphatase-stained osteoclasts in each tumor focus was counted. RESULTS:
      Histomorphometric analysis revealed that YM529 markedly inhibited both the
      formation of bone tumors and the progression of established tumors, as well as
      markedly reducing the number of osteoclasts. CONCLUSIONS: YM529 reduced the tumor
      burden in bone by inhibiting both the formation of new lesions and the
      progression of existing tumors, suggesting that osteoclasts are involved in the
      formation of bone tumors by prostate cancer. Treatment with this bisphosphonate
      may potentially be beneficial for patients with bone metastases of prostate
      cancer.

PMID- 17440968
TI  - Claudin-1 immunohistochemistry for distinguishing malignant from benign
      epithelial lesions of prostate.
AB  - BACKGROUND: Claudins are a family of approximately 23 integral membrane tight
      junction (TJ) proteins that maintain cell polarity and paracellular barrier
      functions in epithelial and endothelial cells. Although Claudin-1 was
      demonstrated to be typically downregulated in various cancers, the precise
      expression patterns of this protein in normal and neoplastic tissues remain
      poorly characterized. METHODS: Using immunohistochemistry, the expression of
      Claudin-1 was investigated in prostate tissue samples arranged in a tissue
      microarray (TMA) format and comprising elements of normal prostatic epithelium (n
      = 6), benign prostatic hyperplasia (BPH; n = 38), prostatic intraepithelial
      neoplasia (PIN; n = 11), and prostate adenocarcinoma (n = 48). The Claudin-1
      expression pattern was compared with that of the basal cell-specific markers,
      p63, and HMW cytokeratin (34betaE12), by employing double-labeling techniques in
      conjunction with image analysis methods utilizing color deconvolution algorithms.
      RESULTS: In benign prostatic epithelium, pronounced Claudin-1 expression was
      observed in the basal cell layer with no staining in luminal cells. Prostate
      adenocarcinoma specimens from 98% (47/48) patients lacked Claudin-1
      immunostaining, and no cases contained >5% immunopositive tumor cells.
      CONCLUSIONS: Claudin-1 immunohistochemistry should be considered for use as a new
      diagnostic tool for distinguishing malignant from benign lesions of the prostate.

PMID- 17440969
TI  - Analysis of the MDM2 antagonist nutlin-3 in human prostate cancer cells.
AB  - BACKGROUND: Small molecule MDM2 antagonists including nutlin-3 have been shown to
      be effective against a range of cancer cell types and nutlin-3 can inhibit growth
      of LNCaP xenografts. We compared the efficacy of nutlin-3 in three prostate
      cancer cell types and provide an insight into the mechanism of nutlin-3. METHODS:
      Nutlin-3 efficacy was measured using proliferation assays, cell cycle analysis,
      apoptosis assays, quantitative RT-PCR, and immunoblotting. Chromatin
      immunoprecipitation (ChIP) assays were also performed. RESULTS: Nutlin-3 can
      specifically inhibit proliferation of LNCaP cells through cell cycle arrest and
      apoptosis. This coincides with increased levels of the p53-responsive transcripts
      p21, PUMA, gadd45, and Mdm2 and recruitment of p53 to chromatin. Nutlin-3 also
      reduces androgen receptor levels, resulting in altered receptor recruitment to
      chromatin. CONCLUSION: Our study demonstrates that small molecule MDM2
      antagonists might be useful in the treatment of human prostate cancers that
      retain functional p53 and androgen receptor signaling.

PMID- 17440970
TI  - In vitro development and cell allocation of porcine blastocysts derived by
      aggregation of in vitro fertilized embryos.
AB  - In pigs, the morphology and cell number of in vitro-produced blastocysts are
      inferior to those of their in vivo counterparts. The objective of this study was
      to increase developmental competence and to gain an understanding of cell
      allocation in blastocysts derived from the aggregation of four-cell stage porcine
      embryos produced in vitro. After removal of the zona pellucida, two (2x) and
      three (3x) four-cell stage embryos were aggregated by co-culturing them in
      aggregation plates. Five days after aggregation, the developmental ability and
      the number of cells in the aggregated embryos were determined. The percentage of
      blastocysts was higher (P < 0.05) in both the 2x and 3x aggregated embryos (66.6%
      and 72.0%, respectively) compared to that of the 1x embryos and the intact
      controls (43.1% and 36.4%, respectively). The total cell number of blastocysts
      also increased in aggregated embryos compared to that of intact controls (2.6
      fold for 2x and 3.4-fold for 3x) (P < 0.05). The cells of two differentially
      stained embryos were started to mix at 72 hr after aggregation. In vitro
      fertilized porcine aggregates (2x) were developed to blastocyst with a random
      distribution of cells from each embryo. The mRNA levels for the oct-4, bcl-xL and
      connexin 43 genes were higher (P < 0.05) and bak gene were lower (P < 0.05) in
      both the 2x and 3x aggregated embryos than the intact controls. Therefore, the
      aggregation of the four-cell stage embryos could be used to improve the quality
      of porcine preimplantation stage embryos produced in vitro.

PMID- 17440971
TI  - A new selection criterion to assess good quality ovine blastocysts after
      vitrification and to predict their transfer into recipients.
AB  - The feasibility to accurately select viable embryos would be valuable for
      improving pregnancy rates and avoiding futile transfer attempts. The aim of our
      study was to assess if in vitro-produced embryo quality could be determined by
      the timing of blastocoelic cavity re-expansion after vitrification, warming, and
      in vitro culture using sheep as a model. Blastocysts were produced in vitro,
      vitrified/warmed, and cultured in TCM-199 plus 10% FCS for 72 hr. Embryos were
      divided into two groups: re-expanded within 8 hr (A) and from 8 to 16 hr (B) of
      IVC after warming. Fast re-expanded blastocysts showed higher in vitro hatching
      rates and total cell number calculated on the hatched blastocysts compared with
      slow re-expanded ones (P < 0.01). Peroxide status evaluation (P < 0.01) and TUNEL
      test (P < 0.05) revealed a higher number of positive cells in group B compared
      with group A. The quantitative analysis of protein synthesis revealed a higher
      synthesis in fast compared with slow re-expanded embryos (P < 0.05). Quantitative
      RT-PCR showed that 90-kDa Heat Shock Protein beta was more expressed in group A
      than in group B (P < 0.05), while the quantity of P34(cdc2), Cyclin b, Aquaporin
      3, Na/K ATPase, and Actin did not differ between the two groups. Pregnancy rates
      after transfer to synchronized recipients were higher in fast compared to slow re
      expanded blastocysts (P < 0.05). Our results evidenced that timing of
      blastocoelic cavity re-expansion after vitrification/warming and in vitro culture
      can be considered as a reliable index of in vitro produced embryo quality and
      developmental potential.

PMID- 17440972
TI  - Vascular density is highest in the proximal region of the mouse prostate.
AB  - BACKGROUND: The proximal region of the prostatic ducts harbor the prostatic
      epithelial stem cells. As stem cell niches in other organs are highly
      vascularized, we determined if the proximal region is more highly vascularized
      than the remaining regions of the prostate. The effect of androgen on vascular
      density in the different prostatic regions was also examined. METHODS: Sections
      from prostates were immunostained with antibodies to CD31, and the vascular
      density in proximal, intermediate, and distal regions was calculated by image
      analysis software. Vascular density was compared in prostates from castrated mice
      that received daily inoculations of testosterone or vehicle alone for 3 days. To
      examine the role of angiogenic factors in the response to androgen, some animals
      were also treated with soluble VEGF receptor-2-Fc or Tie-2--Fc fusion proteins,
      which inhibit the activities of VEGF and angiopoietins, respectively. The
      endothelial proliferative response to androgen was determined by double staining
      sections with antibodies to CD31 and Ki-67. RESULTS: In prostates from intact
      mice, vascular density was highest in the proximal region and lowest in the
      distal region. Administration of testosterone to castrated mice increased
      vascular density to the greatest extent in the distal and intermediate regions.
      The increase in vascular density required VEGF and the angiopoietins. Endothelial
      cell proliferation was less sensitive to androgen in the proximal region than the
      remainder of the prostate. CONCLUSIONS: Vascular density is highest in the
      proximal region of the prostate, but the proximal vessels are less responsive to
      testosterone.

PMID- 17440973
TI  - PIAS1 interacts with and represses SOX9 transactivation activity.
AB  - SOX9 is a transcription factor that harbors a HMG box and plays critical roles in
      developmental processes including sex determination and chondrogenesis. Currently
      the regulation of its molecular activity is not well characterized. In the
      present study, we have identified PIAS1 as a regulator for SOX9 activity. Using
      the GST pull-down, co-immunoprecipitation, and co-localization methods in tissue
      culture cells and mouse embryonic tissues, we demonstrated that SOX9 interacts
      with PIAS1 in vitro and in vivo. PIAS1 enhanced the SUMOylation at lysine 396 of
      mouse SOX9. Mutant SOX9 with a conversion of lysine 396 to arginine had a
      distinct nuclear localization from SOX9 with covalently attached SUMO-1. Effects
      of SOX9 SUMOylation on its transcriptional activity were examined by reporter
      assays using Vanin-1 promoter and Col11a2 enhancer constructs. The lysine 396 to
      arginine conversion significantly increased the reporter gene activity, while
      covalent attachment of SUMO-1 to SOX9 by gene fusion dramatically compromised its
      transcriptional activity on the reporter gene. Effects of SOX9 interaction with
      PIAS1 on its transcriptional activity were examined by similar reporter assays.
      PIAS1 was able to repress both wild type SOX9 and SUMOylation-deficient SOX9
      K396R, suggesting that SOX9 SUMOylation is not absolutely required for the
      repression by PIAS1. However, the repression was further enhanced by exogenous
      SUMO-1 while SUMO-ligase-deficient PIAS1 was not able to repress SOX9 activity.
      Thus, PIAS1 appears to repress SOX9 activity by at least two SUMO-ligase
      dependent mechanisms: (1) the SUMOylation of SOX9 and (2) SUMOylation of unknown
      factors associated with SOX9 and/or PIAS1.

PMID- 17440974
TI  - Cre-conditional expression of constitutively active Notch1 in transgenic mice.
AB  - The Notch signaling pathway plays a critical role during mammalian development.
      To bypass embryonic lethality associated with constitutive Notch1 signaling, we
      created transgenic mice with a floxed beta-geo/stop signal between a cytomegalo
      virus promoter and the constitutively active intracellular domain of Notch1 (IC
      Notch1). IC-Notch1 is activated upon introduction of Cre recombinase and it is
      coexpressed with an enhanced green fluorescent protein or human placental
      alkaline phosphatase reporter. We created three IC-Notch1 transgenic mouse lines
      and crossed them to a general Cre deletor mouse line, pCX-Cre. The double
      transgenic IC-Notch1/pCX-Cre embryos have widespread expression of IC-Notch1 and
      reporters and die before 10.5 days of gestation. Morphological and histological
      analysis of the double transgenic embryos indicated growth arrest and various
      developmental defects, including lack of neural tube closure, disorganized
      somites, and disrupted vasculature. The conditional IC-Notch1 expressing
      transgenic mice provide a unique tool to investigate the Notch pathway using
      tissue-specific Cre mice and inducible Cre systems.

PMID- 17440975
TI  - Factors affecting the in vitro action of cumulus cells on the maturing mouse
      oocytes.
AB  - The removal of cumulus cells (CCs) from oocytes at the germinal vesicle (GV)
      stage still represents a major limitation in such embryo techniques as GV
      transfer, somatic cell haploidization, and oocyte cryopreservation. However, no
      efficient in vitro maturation (IVM) system for CC-denuded oocytes (DOs) has been
      established in mammalian species. Although follicular cells are considered to
      play an important role in oocyte maturation, the specific role and mechanisms of
      action of different cell types are poorly understood. Reports on whether
      junctional association between CCs and the oocyte is essential for the beneficial
      effect of CC co-culture on oocyte maturation are in conflict. Our objective was
      to try to address these issues using the mouse oocyte model. The results
      indicated that while co-culture with the CC monolayer could only partially
      restore the developmental potential of DOs without corona cells, it restored the
      competence of corona-enclosed DOs completely. Culture in medium conditioned with
      CC monolayer also promoted maturation of DOs. However, co-culture with the
      monolayer of mural granulosa cells had no effect. The efficiency of CC co-culture
      was affected by various factors such as density and age of the CCs, the presence
      of gonadotropin in the maturation medium and the duration for in vivo (IVO)
      gonadotropin priming. It is concluded that mouse CCs produce a diffusible
      factor(s) that support DO maturation in a CC-oocyte junctional communication
      dependent manner. The data will contribute to our understanding the mechanisms by
      which CCs promote oocyte maturation and to the establishment of an efficient DO
      IVM system.

PMID- 17440976
TI  - Isolation and characterization of a novel Xenopus gene (xVAP019) encoding a
      DUF1208 domain containing protein.
AB  - We have identified a novel Xenopus gene (xVAP019) encoding a DUF1208 domain
      containing protein. Using whole-mount in situ hybridization and RT-PCR, we found
      abundant xVAP019 maternal transcripts in the animal hemisphere during the
      cleavage stages and blastula stages. During gastrulation xVAP019 is
      differentially expressed with higher levels in the animal helf and the highest in
      marginal zone, then further expressed widely at neuronal stages with strongest
      signals in the prospective CNS regions and the epidermal ectoderm. Subsequently
      xVAP019 was expressed predominantly in the head, the eyes, the otic vesicle,
      branchial arches, spinal cord, notochord, somites, and tailbud. It is absent or
      very weak in the endoderm. Injecting a morpholino oligo complementary to xVAP019
      mRNA or injecting a caped xVAP019 mRNA caused most of embryos to die during
      gastrulation and neurulation. Overexpression of xVAP019 mRNA also led to eye
      defect, shorten interocular distance, small body size and abnormal pigment
      formation in parts of the survival embryos. Similar effects were induced by
      injecting the xVAP019 human homologous gene FAM92A1. Our results suggest that
      xVAP019 is essential for the normal ectoderm and axis mesoderm differentiation
      and embryos survival. This investigation is for the first time in vivo study
      examining the role of this novel gene and reveals an important role of xVAP019 in
      embryonic development.

PMID- 17440977
TI  - Nicotine alters bovine oocyte meiosis and affects subsequent embryonic
      development.
AB  - The effects of nicotine on nuclear maturation and meiotic spindle dynamics of
      bovine oocytes and subsequent embryonic development were investigated. Maturation
      rates (85%-94%) derived from nicotine treatments at 0.01 to 1.0 mM were similar
      to the control (86%), but significantly decreased at 2.0 to 6.0 mM. Haploid
      complements of metaphase II oocytes in 0.01 to 1.0 mM nicotine (approximately
      90%) were similar to the control, while lower (ranged from 63% to 76%, P < 0.05
      or P < 0.01) haploid oocytes were observed in the 2.0 to 6.0 mM nicotine groups.
      The majority of the PB1-free oocytes derived from 3.0 to 6.0 mM nicotine
      treatments were diploidy (2n = 60). Spindle microtubules changed from
      characteristically being asymmetrical in the controls to being equally
      distributed into two separate chromosome groups in the nicotine treatments.
      Nicotine disorganized the microfilament organization and inhibited the movement
      of anaphase or telophase chromosomes to the cortical area. The inhibited two
      chromosome groups became two spindles that either moved close in proximity or
      merged entirely together resulting in diploidy within the affected oocyte.
      Nicotine treatment significantly reduced the rate of cleavage and blastocyst
      development after parthenogenetic activation. Diploidy and cell number were
      drastically reduced in the resultant blastocysts. In conclusion, nicotine can
      alter the normal process of bovine oocyte meiosis and affects subsequent
      embryonic development.

PMID- 17440978
TI  - A meta-analysis of association studies between the 10-repeat allele of a VNTR
      polymorphism in the 3'-UTR of dopamine transporter gene and attention deficit
      hyperactivity disorder.
AB  - The association between the 10-repeat allele of the dopamine transporter gene
      (DAT) and attention deficit hyperactivity disorder (ADHD) is uncertain. This
      study aimed to conduct a meta-analysis of the association between the 10-repeat
      allele of a variable number tandem repeat (VNTR) polymorphism in the 3'
      untranslated region (UTR) of the DAT1 gene and ADHD. We pooled up 18 published
      transmission disequilibrium test (TDT) studies between the 40-base pair VNTR
      polymorphism in the3'-UTR of the DAT1 gene and ADHD. It included a total of 1,373
      informative meioses, 7 haplotype-based haplotype relative risk (HHRR) studies,
      and 6 case-control-based association studies. There were statistically
      significant evidences for heterogeneity of the odds ratio in TDT and HHRR studies
      (P < 0.10), but not in case-control studies. The results of random effects model
      showed small but significant association between ADHD and the DAT1 gene in TDT
      studies (OR = 1.17, 95% CI = 1.05-1.30, chi-square = 8.11, df = 1, P = 0.004),
      but not in HHRR and case-control studies. The 10-repeat allele of a VNTR
      polymorphism in the 3'-UTR the DAT1 gene has a small but significant role in the
      genetic susceptibility of ADHD. These meta-analysis findings support the
      involvement of the dopamine system genes in ADHD liability variation. However,
      more work is required to further identify the functional allelic
      variants/mutations that are responsible for this association.

PMID- 17440979
TI  - Urodynamic changes in a noble rat model for nonbacterial prostatic inflammation.
AB  - BACKGROUND: Chronic nonbacterial prostatitis (CP) associated with voiding
      dysfunction is a poorly understood clinical phenomenon. The goal of the present
      study was to induce prostatic inflammation with estrogen and androgen treatment
      and to record associated urodynamic changes in Noble rats. METHODS: Rats were
      treated with estradiol and testosterone implants to increase estradiol
      concentration in serum while testosterone concentration was maintained at or
      slightly above the control level. The urodynamical recordings were performed
      under anesthesia after the hormone treatments for 3 and 6 weeks. The dorsolateral
      lobes of the prostates were removed for histopathological analysis after
      recordings. RESULTS: After the 3-week treatment, lymphocytes, mainly T-cells,
      were located around the capillaries. During the following 3 weeks lymphocytes
      migrated into stroma and acini. Cytotoxic T-cells were seen intraepithelially,
      and neutrophiles inside the acini. Removal of estrogen implant or treatment with
      anti-estrogen diminished inflammation. No changes in voiding pattern were seen
      after the 3-week treatment. Three weeks later, bladder weight and capacity were
      increased, and the micturition time was prolonged. CONCLUSIONS: Elevated estrogen
      concentration was essential for the gradual development of prostatic
      inflammation. The profile and location of inflammatory cells suggest that
      prostatic vasculature is one of the sites of estrogen action. Urodynamic changes
      which developed in association with glandular inflammation indicated abnormal
      bladder function, reflecting an incipient obstruction.

PMID- 17440980
TI  - Labeling and identification of LNCaP cell surface proteins: a pilot study.
AB  - BACKGROUND: Membrane proteins provide the interface between the cell and its
      environment and are responsible for cell adhesion, mobility, and intracellular
      signaling. Previous studies have focused on the LNCaP whole cell proteome and
      transcriptome but little is known about proteins at the prostate cell membrane
      and how they change in response to androgens. MATERIALS AND METHODS: Following
      treatment with R1881 or vehicle, membrane proteins of the prostate cancer LNCaP
      cell line were tagged with biotin using EZ-link sulfo-NHS-LC-biotin. Using the
      tag membrane proteins were purified and separated using two-dimensional gel
      electrophoresis and identified using mass spectrometry. E-cadherin and low
      density lipoprotein receptor (LDLR) were used as positive controls and also
      investigated following bicalutamide treatment. Membrane localization and androgen
      regulation of proteins was confirmed using sub-cellular fractionation, Western
      blotting and microscopy. RESULTS: We have demonstrated efficient and specific
      protein biotinylation and purification of LNCaP plasma membrane proteins using
      Western analysis. E-cadherin and LDLR were regulated at the cell surface in
      response to R1881 and bicalutamide. Mass spectrometry identified several androgen
      regulated membrane associated proteins including Prx-3 and GRP78 which are known
      to localize to other cellular compartments as well as the plasma membrane. We
      confirmed the localization of the identified proteins in LNCaP cells by co
      localization with E-cadherin and immunohistochemistry of prostate tissue.
      CONCLUSION: Cell surface biotinylation is an effective technique for identifying
      membrane proteins in the LNCaP prostate cancer cell line. We have demonstrated
      the identification of androgen-regulated membrane proteins and their validation
      in tissue samples.

PMID- 17440981
TI  - Biallelic germline mutations of mismatch-repair genes: a possible cause for
      multiple pediatric malignancies.
AB  - BACKGROUND: Heterozygous defects in mismatch-repair (MMR) genes cause hereditary
      nonpolyposis colorectal cancer (HNPCC). In this syndrome, tumors typically arise
      from age 25 years onward. Case reports have shown that homozygosity or compound
      heterozygosity for MMR gene mutations can cause multiple tumors in childhood,
      sometimes combined with neurofibromatosis type I (NF1)-like features. Therefore,
      the authors studied the role of homozygosity or compound heterozygosity (CZ) for
      MMR gene defects in children with multiple primary tumors. METHODS: A database
      that contained all pediatric oncology patients who were seen between 1982 and
      2003 at the author's institution was queried to identify patients aged <16 years
      with more than 1 tumor for whom tissue of at least 1 tumor was available. On
      isolated DNA, microsatellite instability (MSI) and immunohistochemistry of MMR
      proteins were assessed. RESULTS: In total, 15 patients with more than 1 tumor
      were identified. Abnormal test results were obtained in 2 of them, including 1
      patient who was diagnosed at age 4 years with a glioblastoma (MSI-stable; no
      human mutL homolog 1 [MLH1] or postmeiotic segregation increased, Saccharomyces
      cerevisiae 2 [PMS2] expression) and a Wilms tumor (high MSI; no MLH1 or PMS2
      expression). Apart from >6 cafe-au-lait spots, he had no other signs of NF1. The
      patient had CZ identified for a pathogenic MLH1 mutation (593delAG frameshift)
      and an unclassified MLH1 variant (Met35Asn). There was strong evidence that this
      unclassified variant was a pathogenic mutation. The second patient was diagnosed
      with a non-Hodgkin lymphoma (no tissue available) and an anaplastic
      oligodendroglioma (low MSI; no MSH6 expression) at age 4 years and 6 years,
      respectively. His brother had died of a medulloblastoma at age 6 years (low MSI,
      no MSH6 expression). Both boys had cafe-au-lait spots. Further genetic testing
      was not possible. CONCLUSIONS: Carriage of biallelic MMR gene defects can be
      associated with multiple malignancies in childhood that may differ from the
      standard spectrum of HNPCC tumor types. In 15 pediatric patients with multiple
      malignancies, the authors identified 1 clear case and 1 possible case of
      biallelic MMR gene defect. Recognition of the inherited nature of the tumors in
      these patients is important for counseling these patients and their families.

PMID- 17440982
TI  - Limited feasibility of double transplant in multiple myeloma: results of a
      multicenter study on 153 patients aged <65 years.
AB  - BACKGROUND: Although high-dose therapy is considered the standard therapy for
      younger patients with multiple myeloma (MM), the advantages of performing a
      second transplant remain debated. The current study was conducted to evaluate the
      efficacy and the feasibility of a front-line double transplant program in young
      MM patients. METHODS: A total of 153 MM patients aged <or=65 years, the majority
      of whom had stage III disease (65%), were enrolled in a multicenter,
      nonrandomized, high-dose program including 2 transplants. RESULTS: The percentage
      of good quality responses (complete and very good partial responses) increased
      from an initial 33% after induction to 91% (complete response rate of 29%) after
      2 transplants. However, this increase in response did not produce an advantage in
      either event-free survival or overall survival, even when the analysis was
      performed grouping patients by response. The protocol was well tolerated and no
      difference in transplant-related mortality was observed between the first and
      second transplants. A first transplant was performed in 122 of 153 patients
      (80%), and 65 (42% of the enrolled patients) completed the double transplant
      program. Reasons for not undergoing the second autologous transplant were death
      (n=2 patients), insufficient peripheral blood stem cells (n=8 patients), severe
      transplant-related toxicity (n=10 patients), allotransplants (n=9 patients),
      early progression after first transplant (n=6 patients), lost to follow-up (n=3
      patients), and patient refusal (n=19 patients). CONCLUSIONS: Considering the
      limited advantage of double transplants, the complexity of the program, the high
      percentage of dropouts, and the additional costs of a second transplant, the
      current study favors single transplant programs for the treatment of younger MM
      patients.

PMID- 17440983
TI  - Prognostic relevance of the mTOR pathway in renal cell carcinoma: implications
      for molecular patient selection for targeted therapy.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) pathway is up-regulated in
      many human cancers, and agents targeting the mTOR pathway are in various stages
      of clinical development. The goal of the study was to evaluate the potential and
      limitations of targeting the mTOR pathway in renal cell carcinoma (RCC). METHODS:
      Immunohistochemical analysis using antibodies against pAkt, PTEN, p27, and pS6
      was performed on a tissue microarray constructed from paraffin-embedded specimens
      from 375 patients treated by nephrectomy for RCC. The expression was associated
      with pathological parameters and survival. RESULTS: The mTOR pathway was more
      significantly altered in clear-cell RCC, high-grade tumors, and tumors with poor
      prognostic features. PS6 and PTEN showed the strongest associations with
      pathological parameters. Survival tree analysis regarding expression of
      cytoplasmic pAkt, nuclear pAkt, PTEN, cytoplasmic p27, and pS6 identified
      staining percentages of 40%, 10%, 75%, 7%, and 70%, respectively, as ideal cutoff
      values for stratification, with corresponding P-values of .03, .001, .02, .005,
      and <.0001, respectively. Interestingly, high nuclear pAkt expression was
      associated with a favorable prognosis, whereas high cytoplasmic pAkt expression
      was associated with a poor prognosis. In multivariate Cox regression analysis,
      ECOG PS, T classification, N classification, M classification, cytoplasmic Akt,
      nuclear pAkt, PTEN, and pS6 were independent prognostic factors of DSS.
      CONCLUSIONS: Components of the mTOR pathway are significantly associated with
      pathological features and survival. Not all RCC tumor types seem to be equally
      amenable to mTOR targeted therapy. PTEN, pAkt, p27, and pS6 may serve as
      surrogate parameters for patient selection and predicting prognosis. Patients
      with a highly activated mTOR pathway should benefit most from this therapy.
      External validation of our results is recommended.

PMID- 17440984
TI  - Clinical correlates of JAK2V617F allele burden in essential thrombocythemia.
AB  - BACKGROUND: JAK2V617F occurs in approximately 50% of patients with essential
      thrombocythemia (ET). Qualitative studies of mutation analysis have previously
      reported an association between JAK2V617F and advanced age, higher hemoglobin
      level, higher leukocyte count, and lower platelet count. A possible association
      with thrombotic complication has also been considered. METHODS: Allele-specific,
      quantitative polymerase chain reaction (PCR) analysis for JAK2V617F was performed
      in 176 patients with ET using genomic DNA from archived bone marrow, which was
      collected within 1 year (n=72 patients), between 1 and 5 years (n=64 patients),
      or after 5 years (n=40 patients) of diagnosis. RESULTS: JAK2V617F was detected in
      96 patients (55%), in whom mutant allele burden ranged from 1% to 100% (median,
      6.3%). Neither mutational frequency (P=.37) nor mutant allele burden (P=.62) was
      affected by the timing of bone marrow sample collection. The presence of
      JAK2V617F was found to be significantly associated with higher hemoglobin level
      (P<.0001), lower platelet count (P=.001), higher leukocyte count (P=.008),
      increased incidence of venous thrombosis occurring after diagnosis (P=.02), and
      older age at diagnosis (P=.03). All but age retained significance in
      multivariable analysis. In mutation-positive patients (n=96 patients), JAK2V617F
      allele burden clustered between 1% and 22% in 94 cases, in whom it correlated
      directly and significantly with platelet and leukocyte counts, palpable
      splenomegaly at diagnosis, and venous thrombosis occurring after diagnosis. The
      latter 2 associations remained significant with the inclusion of the remaining 2
      outlier cases with 100% mutant allele burden; in addition, an association with
      male gender became evident. CONCLUSIONS: JAK2V617F allele burden imparts
      additional phenotypic effects in ET.

PMID- 17440985
TI  - Morphological aspects of gonadal morphogenesis in Bufo bufo (Amphibia Anura):
      Bidder's organ differentiation.
AB  - We have described the architecture of Bidder's organ, defined its compartmented
      structure, and affirmed the presence of basal laminae. We did not find
      morphological differences between sexes in Bidder's organ. All specimens
      initially developed gonads with a peripheral fertile layer surrounding a thin
      primary cavity. The first oogenetic wave was observed early, showing all phases
      of meiosis, including leptotene, zygotene, and pachytene, which had been
      previously thought to be lacking. The peculiar presence of an asynchronous germ
      cell nest was discussed. Diplotene oocytes issued from the peripheral layer and
      migrated inside the primary cavity. They were surrounded by a single layer of
      follicular cells, which originated from the peripheral layer somatic cells and
      were delimited by a basal lamina. There were few medulla or central layer cells.
      At the end of metamorphosis, while the oocytes of the first oogenetic wave came
      into close contact with blood vessels, a second oogenetic wave took place just as
      the first, except for the presence of synchronous germ cell nests. The central
      layer was not visible and we did not observe the formation of an ovarian pocket.
      Stocks of stem germ cells remained in the peripheral layer during both the first
      and second oogenetic waves. The asymmetric model, in which there is a tendency
      toward a primary female differentiation, was confirmed. The female
      differentiation becomes stable in the Bidder's organ because of the absence of
      further interaction between germ and medullary somatic cells, which would have
      led toward a male differentiation.

PMID- 17440986
TI  - Developmental potential of Gcn5(-/-) embryonic stem cells in vivo and in vitro.
AB  - Gcn5 is a prototypical histone acetyltransferase (HAT) that serves as a
      coactivator for multiple DNA-bound transcription factors. We previously
      determined that deletion of Gcn512 (hereafter referred to as Gcn5) causes
      embryonic lethality in mice. Gcn5 null embryos undergo gastrulation but exhibit
      high levels of apoptosis, leading to loss of mesodermal lineages. To further
      define the functions of Gcn5 during development, we created Gcn5(-/-) mouse
      embryonic stem (ES) cells. These cells survived in vitro and formed embryoid
      bodies (EBs) that expressed markers for ectodermal, mesodermal, and endodermal
      lineages. Gcn5(-/-) EBs were misshapen and smaller than wild-type EBs by day 6,
      with an increased proportion of cells in G2/M. Expression of Oct 4 and Nodal was
      prematurely curtailed in Gcn5(-/-) EBs, indicating early loss of pluripotent ES
      cells. Gcn5(-/-) EBs differentiated efficiently into skeletal and cardiac muscle,
      which derive from mesoderm. High percentage Gcn5(-/-) chimeric embryos created by
      injection of Gcn5(-/-) ES cells into wild-type blastocysts were delayed in
      development and died early. Interestingly, elevated levels of apoptosis were
      observed specifically in Gcn5 null cells within the chimeric embryos.
      Collectively, these data indicate that Gcn5 may be required to maintain
      pluripotent states and that loss of Gcn5 invokes a cell-autonomous pathway of
      cell death in vivo.

PMID- 17440988
TI  - Evolutionary conservation and divergence of the segmentation process in
      arthropods.
AB  - A fundamental characteristic of the arthropod body plan is its organization in
      metameric units along the anterior-posterior axis. The segmental organization is
      laid down during early embryogenesis. Our view on arthropod segmentation is still
      strongly influenced by the huge amount of data available from the fruit fly
      Drosophila melanogaster (the Drosophila paradigm). However, the simultaneous
      formation of the segments in Drosophila is a derived mode of segmentation.
      Successive terminal addition of segments from a posteriorly localized
      presegmental zone is the ancestral mode of arthropod segmentation. This review
      focuses on the evolutionary conservation and divergence of the genetic mechanisms
      of segmentation within arthropods. The more downstream levels of the segmentation
      gene network (e.g., segment polarity genes) appear to be more conserved than the
      more upstream levels (gap genes, Notch/Delta signaling). Surprisingly, the
      basally branched arthropod groups also show similarities to mechanisms used in
      vertebrate somitogenesis. Furthermore, it has become clear that the activation of
      pair rule gene orthologs is a key step in the segmentation of all arthropods.
      Important findings of conserved and diverged aspects of segmentation from the
      last few years now allow us to draw an evolutionary scenario on how the
      mechanisms of segmentation could have evolved and led to the present mechanisms
      seen in various insect groups including dipterans like Drosophila.

PMID- 17440987
TI  - Type I collagen is a genetic modifier of matrix metalloproteinase 2 in murine
      skeletal development.
AB  - Recessive inactivating mutations in human matrix metalloproteinase 2 (MMP2,
      gelatinase A) are associated with syndromes that include abnormal facial
      appearance, short stature, and severe bone loss. Mmp2(-/-) mice have only mild
      aspects of these abnormalities, suggesting that MMP2 function is redundant during
      skeletal development in the mouse. Here, we report that Mmp2(-/-) mice with
      additional mutations that render type I collagen resistant to collagenase
      mediated cleavage to TC(A) and TC(B) fragments (Col1a1(r/r) mice) have severe
      developmental defects resembling those observed in MMP2-null humans. Composite
      Mmp2(-/-);Col1a1(r/r) mice were born in expected Mendelian ratios but were half
      the size of wild-type, Mmp2(-/-), and Col1a1(r/r) mice and failed to thrive.
      Furthermore, composite Mmp2(-/-);Col1a1(r/r) animals had very abnormal
      craniofacial features with shorter snouts, bulging skulls, incompletely developed
      calvarial bones and unclosed cranial sutures. In addition, trabecular bone mass
      was reduced concomitant with increased numbers of bone-resorbing osteoclasts and
      osteopenia. In vitro, MMP2 had a unique ability among the collagenolytic MMPs to
      degrade mutant collagen, offering a possible explanation for the genetic
      interaction between Mmp2 and Col1a1(r). Thus, because mutations in the type I
      collagen gene alter the phenotype of mice with null mutations in Mmp2, we
      conclude that type I collagen is an important modifier gene for Mmp2.
      Developmental Dynamics 236:1683-1693, 2007. (c) 2007 Wiley-Liss, Inc.

PMID- 17440989
TI  - Highly variable penetrance in subjects affected with cavernous cerebral angiomas
      (CCM) carrying novel CCM1 and CCM2 mutations.
AB  - Cavernous vascular malformations may affect brain and out-of-brain tissues. In
      most cases, cerebral cavernous malformations (CCMs) involve the brain alone, and
      are rarely associated with skin hemangiomas, spinal cord, retinal, hepatic or
      vertebral lesions. CCMs can cause seizures, intracranial and spinal haemorrhages,
      focal neurological deficits, and migraine-like headaches. After collecting CCM
      families of Italian origin and investigating the genetic basis of the disorder we
      disclosed two novel molecular variations in the KRIT1 and MGC4607 genes. We found
      a novel CCM1 gene mutation (Q66X) in a family with apparently asymptomatic old
      aged mutation carriers and patients who either had skin angiomas alone or the
      full association of cerebral, spinal, and skin lesions. In this family we report
      the highest variability in mutation penetrance so far described, including the
      presence of CCM in one subject since birth (surgery at 19 months of age), a
      condition to our knowledge so far unreported. In a CCM2 affected family, we also
      report a novel causative mutation, (54_55delAC) in exon 2 of the MGC4607 gene,
      that produces a truncated protein containing only 22 amino acids. These data
      describe novel CCM mutations associated with a particularly high variability of
      the penetrance causing, in some cases, reduced expression of clinical symptoms
      and sporadic cases with apparent negative family history. Hence they emphasize
      the importance of DNA-based diagnostics and genetic counseling to identify
      unaffected mutation carriers subjects, even at advanced age.

PMID- 17440990
TI  - Inhibition of human recombinant cytochromes P450 CYP1A1 and CYP1B1 by trans
      resveratrol methyl ethers.
AB  - CYP1A1 and CYP1B1 are the inducible forms of cytochrome P450 expressed in
      extrahepatic tissues, which are responsible for the biotransformation of
      polycyclic aromatic hydrocarbons, heterocyclic amines and estradiol to the
      carcinogenic intermediates. The aim of our research was to determine and compare
      the inhibitory effect of naturally occurring analogues of trans-resveratrol on
      the catalytic activities of human recombinant CYP1A1 and CYP1B1. Pinostilbene
      (3,4'-dihydroxy-5-methoxystilbene), desoxyrhapontigenin (3,5-dihydroxy-4'
      methoxystilbene), and pterostilbene (3,5-dimethoxy-4'-hydroxystilbene) appeared
      to be very potent inhibitors of CYP1A1 catalytic activity with Ki values of 0.13,
      0.16 and 0.57 microM, respectively. Results from this study indicate that trans
      resveratrol analogues in which the hydroxy groups are substituted by methoxy
      groups exhibit a remarkably stronger inhibitory effect towards CYP1A1 in
      comparison to the parent compound. On the contrary, the potency of pinostilbene,
      desoxyrhapontigenin and pterostilbene towards CYP1B1 with Ki values of 0.90, 2.06
      and 0.91 microM, respectively, was comparable to that of resveratrol. It appears
      that between these analogues, inhibition of CYP1A1 and CYP1B1 catalytic
      activities does not vary much regardless of the number and position of
      methylether substitution. The results suggest that the trans-resveratrol
      analogues: pinostilbene, desoxyrhapontigenin and pterostilbene, which occur in
      some food plants, might be considered as promising chemopreventive agents.

PMID- 17440991
TI  - Heme oxygenase induction by cyanidin-3-O-beta-glucoside in cultured human
      endothelial cells.
AB  - The aim of the present research was to investigate the effect of cyanidin-3-O
      beta-glucoside (C3G) on heme oxygenase-1 (HO-1), endothelial nitric oxide
      synthase (eNOS), inducible NOS (iNOS) and dimethylarginine dimethylamino
      hydrolase-2 (DDAH-2) expression in cultured endothelial cells. Different
      concentrations (0.00625-250 microM) of C3G were tested in order to investigate
      possible beneficial and harmful effects of C3G. Our data demonstrated that C3G
      increased the induction of eNOS and HO-1 in a dose-dependent manner. Higher
      concentration (62.5-250 microM) also resulted in increase of isoprostane, cGMP
      and PGE2 levels and in induction of iNOS with consequent oxidative stress. In
      conclusion, our data evidence that C3G may exert various protective effects
      against endothelial dysfunction, whereas potentially harmful effects of C3G
      appear to be limited to concentrations very difficult to be reached in
      physiological conditions unless there is abundant oral supplementation.

PMID- 17440992
TI  - Antiinflammatory and antifibrogenic effects of s-ethyl cysteine and s-methyl
      cysteine in the kidney of diabetic mice.
AB  - Protective effects of s-ethyl cysteine (SEC) and s-methyl cysteine (SMC) in
      kidney of diabetic mice were examined. SEC and SMC at 0.5, 1, 1.5, 2 g/L were
      added to the drinking water for 6 wk. Results showed that the intake of SEC or
      SMC alleviated body weight loss and urine output, as well as markedly decreased
      plasma blood urea nitrogen (BUN) and creatinine clearance (CCr) in diabetic mice
      (P < 0.05). The intake of SEC caused significantly dose-dependent increase in
      insulin and decrease in blood glucose, urinary albumin and type IV collagen (P <
      0.05). SEC and SMC intake significantly and dose-dependently decreased
      malondialdehyde level and increased glutathione content in kidney (P < 0.05). The
      intake of these agents also increased renal GPx activity (P < 0.05), but there
      was no dose-dependent effect. SEC treatments dose-dependently decreased IL-6 and
      TNF-alpha levels, increased IL-4 and IL-10 levels, as well as upregulated IL-10
      mRNA expression (P < 0.05). SMC treatments significantly suppressed renal IL-6
      and TNF-alpha levels (P < 0.05), but did not affect IL-4 and IL-10 levels (P <
      0.05). SEC or SMC intake significantly suppressed renal TGF-beta1 level and renal
      PKC activity (P < 0.05); however, only SEC treatments showed dose-dependent
      effect. SEC and SMC treatments significantly down-regulated mRNA expression of
      renal TGF-beta1 (P < 0.05), only SEC treatments had dose-dependent effects. Based
      on the observed antioxidative, antiinflammatory, and antifibrogenic effects, the
      supplement of SEC or SMC might be helpful for the prevention or treatment of
      diabetic kidney diseases.

PMID- 17440993
TI  - Glucosamine inhibits LPS-induced COX-2 and iNOS expression in mouse macrophage
      cells (RAW 264.7) by inhibition of p38-MAP kinase and transcription factor NF
      kappaB.
AB  - Glucosamine supplements are very promising nonsteroidal anti-inflammatory agents
      widely used for the treatment of arthritis in animals and humans. In this study,
      we have proposed the molecular mechanism underlying the anti-inflammatory
      properties of glucosamine hydrochloride (GLN) using mouse macrophage cell line
      (RAW 264.7). Treatment with GLN inhibited LPS-stimulated nitric oxide (NO)
      production. Western blotting and RT-PCR analysis showed that GLN treatment
      decreased LPS-induced inducible nitric-oxide synthase (iNOS) and cyclooxygenase-2
      (COX-2) protein and mRNA expression in RAW 264.7 cells, respectively. To further
      elucidate the mechanism of inhibitory effect of GLN, we studied the LPS-induced
      phosphorylation of mitogen-activated protein kinases (pp44/42 and pp38). Our
      results clearly indicated that GLN treatment resulted in a reduction of pp38,
      whereas activation of p44/42 was not affected. In addition, LPS-induced
      activation of nuclear factor-kappaB (NF-kappaB) DNA binding suggests an
      inhibitory effect of GLN. These results indicate that GLN suppresses the LPS
      induced production of NO, expression of iNOS and COX-2 by inhibiting NF-kappaB
      activation and phosphorylation of p38 MAP kinase.

PMID- 17440994
TI  - An integrated sample preparation to determine coccidiostats and emerging Fusarium
      mycotoxins in various poultry tissues with LC-MS/MS.
AB  - The usefulness of an existing sample preparation technique used for ionophoric
      coccidiostats (lasalocid, monensin, salinomycin and narasin) was applied in the
      analysis of emerging Fusarium-mycotoxins beauvericin (BEA) and enniatins (ENNs)
      in poultry tissues (liver and meat). Also, maduramicin and liver as a new sample
      matrix was introduced. The developed methods were validated and applied for the
      determination of coccidiostats and BEA/ENNs in Finnish poultry tissues in 2004
      2005. The validation parameters demonstrated that the integrated sample
      preparation technique is applicable to the parallel determination of these
      contaminants in poultry tissues. Of the samples analysed (276 meat and 43 liver),
      only trace levels of LAS, MON, SAL, NAR and MAD were detected in 7, 3, 5, 6 and
      4% of the samples, respectively. Interestingly, for the first time, traces of BEA
      and ENNs could also be detected in animal tissues. BEA and ENNs A, A1, B and B1
      were found in 2, 0.3, 0.6, 4 and 3% of the samples, respectively. The
      simultaneous presence of coccidiostats and mycotoxins was detected in three
      turkey samples in 2004.

PMID- 17440995
TI  - Green tea catechins upregulate superoxide dismutase and catalase in fruit flies.
AB  - Chinese Longjing green tea is an excellent source of polyphenol antioxidants.
      HPLC analysis revealed that Longjing green tea catechin extract (GTC) contained
      62% epigallocatechin gallate (EGCG), 19% epigallocatechin (EGC), 9% epicatechin
      gallate (ECG), and 7% epicatechin (EC). Investigating the effect of GTC on the
      lifespan of Drosophila melanogaster, we observed that a 10 mg GTC/mL diet could
      prolong its 50% survival time by 36% and mean lifespan by 16%. This was
      consistent with 17% reduction in total body lipid hydroperoxide (LPO) level in
      GTC-treated flies compared to the control group. Supplementation of 10 mg GTC/mL
      diet increased the survival time only in wild type Oregon-R-C (OR) but not in two
      mutant fly lines, SOD(n108)/TM3 (gene for superoxide dismutase (SOD) was knocked
      out) and Cat(n1)/TM3 (gene for catalase was knocked out), when the flies were
      challenged with paraquat or hydrogen peroxide. Accordingly, SOD and catalase
      activities in OR wild type increased by 40 and 19%, respectively. RT-PCR analysis
      indicated that the genes for copper-zinc containing SOD (CuZnSOD), manganese
      containing SOD (MnSOD), and catalase were upregulated. It was concluded that
      prolonging lifespan by GTC in D. melanogaster was influenced, among others, by
      upregulation of endogenous antioxidant enzymes.

PMID- 17440996
TI  - Dose effects of the food spice cardamom on aspects of hamster gut physiology.
AB  - The dose effects of pectic polysaccharide-rich extract from the food spice
      cardamom (Amomum villosum Lour.) on intestinal environment were investigated. The
      results showed that pectic polysaccharides and hemicellulose were the major
      polysaccharides in the cardamom extract. The administration of cardamom extract
      (0.5 and 1.5 g/100 g diet) effectively (p < 0.05) shortened hamster
      gastrointestinal transit time by approximately 58%, increased fecal moisture
      contents (148-174%), increased SCFA concentrations in hindgut (4.0- to 7.8-fold),
      decreased the activities of beta-D-glucuronidase (by 71.4-85.7%), beta-D
      glucosidase (by 24.3-51.5%), mucinase (by 63.6-72.7%), and urease (by 88.8-90.4%)
      in feces, and reduced the production of toxic ammonia (by 16.1-64.5%). These
      findings suggested that the consumption of cardamom extract (at least 0.5 g/100 g
      diet or 40 mg/day) might exert a favorable effect on improving the
      gastrointestinal milieu, and also provide a clue to substantiate its traditional
      therapeutic uses and dosage for intestinal health improvement.

PMID- 17440997
TI  - Importance of a canteen lunch on the dietary intake of acrylamide.
AB  - A food and drink intake survey was carried out among university students and
      staff members. Consumption data were collected on days when the participants took
      hot lunch in a university canteen. The dietary acrylamide exposure was calculated
      through a probabilistic approach and revealed a median intake of 0.40 microg/kg
      bw/day [90% confidence interval: 0.36-0.44], which is in accordance with previous
      exposure calculations. Biscuits (35.4%), French fries (29.9%), bread (23.5%), and
      chocolate (11.2%) were identified to be the main sources of dietary acrylamide.
      Foodstuffs consumed in between the three main meals of the day (so called snack
      type foods) contributed the most to the intake (42.2%). The exposure was lower in
      an intervention group which received free portions of fruit and vegetables,
      indicating that a nutritionally balanced diet may contribute to a decreased
      acrylamide intake. French fries had a significant impact on the acrylamide
      intake, due to the frequent consumption in the canteen. This demonstrates the
      important responsibility of caterers and canteen kitchens in the mitigation of
      acrylamide exposure through reduction of acrylamide in their prepared products,
      in particular in French fries.

PMID- 17440998
TI  - Factor VII polymorphisms influence the plasma response to diets with different
      fat content, in a healthy Caucasian population.
AB  - To determine the influence of the factor VII gene polymorphisms, R353Q and 5'F7,
      on factor VII Ag plasma levels after the consumption of diets with different fat
      contents. METHODS: 59 healthy individuals (42 RR, 16 RQ, 1 QQ at the R353Q and 46
      A1A1, 13 A1A2 at the 5'F7) consumed 3 diets during 4-weeks each: a Saturated diet
      (SAT) enriched in saturated fatty acid (SFA) (38% fat, 20% SFA), followed by a
      carbohydrate (CHO)-rich diet (30% fat, 55% CHO) or a Mediterranean diet (MEDIT)
      enriched in monounsaturated fatty acid (MUFA) (38% fat, 22% MUFA) following a
      randomized crossover design. Plasma lipids and FVII Ag plasma levels were
      determined at the end of each dietary period. RESULTS: After a SAT diet, RR
      homozygotes had greater concentrations of FVII Ag compared with MEDIT and CHO
      diets than did carriers of the minority Q allele (82.76 +/- 1.3 vs. 75.02 +/-
      2.4, p = 0.001). The 5'F7 polymorphism behaved in a similar fashion (A1A1 81.98
      +/- 1.4 vs. A1A2 75.37 +/- 2.4, p = 0.026). CONCLUSIONS: Our data show that
      carriers of the RR and/or A1A1 genotype present higher FVII Ag levels after the
      consumption of a SAT diet compared with the MEDIT and CHO rich diets.

PMID- 17440999
TI  - Angiotensin-converting enzyme activity in plasma and tissues of spontaneously
      hypertensive rats after the short- and long-term intake of hydrolysed egg white.
AB  - This paper evaluates the effects of the short- (1 g/kg) and long-term (0.5 and 1
      g/kg/day) oral intake of egg white hydrolysed with pepsin (hEW) and the long-term
      oral intake (1 g/kg/day) of egg white (EW) on local angiotensin-converting enzyme
      (ACE) activities in plasma and other tissues of spontaneously hypertensive rats
      (SHR), as compared to the effect of the ACE inhibitor prototype captopril. The
      rats treated with hEW were classed in a different group than the control rats and
      the rats treated with EW by cluster analysis, taking into account their tissue
      ACE activities and their systolic blood pressure (SBP). Principal component
      analysis (PCA) showed that SBP in SHR was negatively related with ACE activity in
      plasma and positively related with ACE activity in aorta and kidney. ACE activity
      in plasma significantly increased after the long-term treatment with hEW (0.5
      g/kg/day). ACE activity in aorta and kidney was significantly inhibited 4 h after
      the short-term administration of hEW. The long-term treatment with hEW caused
      local effects on ACE activity in aorta, kidney and lungs that followed a pattern
      similar, but less pronounced, than that caused by captopril.

PMID- 17441000
TI  - Effect of MAO A deficiency on different kinds of aggression and social
      investigation in mice.
AB  - Monoamine oxidase A (MAO A) degrades serotonin, dopamine and noradrenaline,
      factors critically involved in the regulation of aggression. Different kinds of
      aggression were investigated in Tg8, a transgenic mouse strain lacking a
      functional MAO A gene. MAO A-deficient mice differ from wild-type C3H/HeJ (C3H)
      in terms of showing higher territorial, predatory and isolation-induced
      aggression. Tg8 demonstrated shorter latencies to cricket killing and to the
      first attack after 6 weeks isolation than C3H mice. In the resident-intruder
      paradigm, MAO A-lacking mice were more aggressive than C3H when tested as
      intruders. In contrast to C3H, attack in Tg8 mice did not depend on different
      aggressiveness of intruders of BALB/c, A/Sn and C3H strains. Tg8 mice displayed
      no increase in aggression but demonstrated reduced social investigation towards
      anesthetized, as well as towards juvenile BALB/c males. Thus, MAO A deficiency in
      Tg8 mice is accompanied by increased expression of different kinds of aggression,
      as well as by disruption of normal pattern of social interaction.

PMID- 17441001
TI  - Estimation of the probability of fighting in fallow deer (Dama dama) during the
      rut.
AB  - Fighting between males is a frequent component of the rutting behavior of
      Cervidae. Frequent conflicts are exhausting; fighting may be risky and can lead
      to serious injuries or even death. We focused on the process of assessment of the
      opponent's fighting ability and escalation of the combat, estimating the
      probability of fighting based on the encounter components such as groaning and
      parallel walk. In this study, we observed the agonistic behavior of fallow deer
      bucks (Dama dama) during the rut over four seasons. During this time, we recorded
      205 encounters between bucks. Non-contact display, which allows contestants to
      assess their opponents fighting ability, occurred in 83% of the encounters. The
      highest predicted probability of a fight was found when both of the males
      vocalized and turned into the parallel walk. The chance of a clear outcome
      decreased when the males were fighting in comparison to when they did not fight.
      The initiator of the competitive encounter won 41% of the cases, while the
      attacked buck won 23% of the encounters. If the contestants avoided fighting,
      however, the initiator won 78% of encounters. Therefore, the initiator was more
      successful when no fight occurred compared to when the encounters escalated into
      fighting. In most cases where ritualized behavior occurred, one of the opponents
      left after vocalization or parallel walk occurred. Thus, vocalization and
      parallel walk increased the probability for a clear outcome. The probability of a
      fight was lowest in situations where the males displayed asymmetric behavior.
      Increased symmetry of the contestants' behavior was strongly correlated with a
      higher probability of a fight. Thus, these results indicate that fallow deer
      bucks use efficient tactic during the rut, which, in turn, minimizes the chance
      of injury while fighting during the breeding season.

PMID- 17441002
TI  - A preliminary examination of the intergenerational continuity of maternal
      psychopathic features.
AB  - The study provided a preliminary test of the intergenerational continuity of
      maternal psychopathic features in a non-referred elementary aged sample of
      children. Consistent with dominant etiological models and recent behavioral
      genetics research, a direct association was expected between maternal and child
      affective features of psychopathy (i.e., callous-unemotional or CU traits).
      Potential mediators representative of alternative transmission mechanisms were
      assessed including parenting dysfunction, parental hostility/interpersonal
      insensitivity, and child impulsivity. Behavioral features of psychopathy were
      also assessed and were predicted to bear weaker and more indirect parent-child
      associations. A mixed sex sample of 83 children accompanied by a biological
      mother were administered a multi-informant rating-scale battery including
      separate parent (i.e., Levenson Self-Report Psychopathy Scale) and child (i.e.,
      Antisocial Process Screening Device) measures of psychopathy. Consistent with
      prediction, a significant association was documented between maternal and child
      CU traits (r=.22). Additionally, a slightly weaker association and statistical
      trend (r=.21) was observed in the relation between maternal and child
      interpersonal features of the psychopathy construct. Contrary to prediction, all
      documented associations were fully mediated by parental hostility and parenting
      dysfunction. Given the preliminary nature of study findings, implications for
      developmental modeling and future intergenerational continuity research are
      discussed.

PMID- 17441003
TI  - Age differences in the prevalence of physical aggression among 5-11-year-old
      Canadian boys and girls.
AB  - It has been proven extremely difficult in the past to estimate the prevalence of
      physical aggression in children for two main reasons: (a) a heterogeneous
      sampling of behaviors (i.e., mix between physically aggressive and non-physically
      aggressive antisocial behaviors), and (b) a lack of a "gold standard" to identify
      children who exhibit physically aggressive behaviors on a frequent basis. The
      goal of this study was to test for age differences in the prevalence of physical
      aggression in the Canadian population of school-aged boys and girls, using cross
      sectional data from the National Longitudinal Survey of Children and Youth
      (NLSCY). The first wave of the NLSCY included a representative sample of 12,292
      Canadian children aged 5-11 years. We used latent class analysis to identify
      children whose propensity to exhibit physically aggressive behaviors was much
      higher than that of other children of the same age and sex in the population. The
      prevalence of physical aggression was estimated at 3.7% in 5-11-year-old boys and
      ranged from .5% to 2.3% in 11 and 5-year-old girls, respectively. Hence, the
      results show a decreasing trend in the prevalence of physical aggression with age
      for girls, but not for boys. These findings suggest the importance of considering
      the developmental pathways of physical aggression for boys and girls separately.

PMID- 17441004
TI  - Ontogeny of sex differences in defensive burying behavior in rats: effect of
      social isolation.
AB  - The aim of the present experiments was to clarify sex differences in socio
      developmental factors that affected defense behavior in rats. Sex differences in
      the defensive burying behavior of rats, and related social factors, were explored
      in three developmental stages: juvenile, puberty, and adult; 30, 50, and 80 days
      of age, respectively. The duration of burying, digging into bedding material,
      stretch-attend postures, and crouch/freezing were measured in a shock-prod test.
      For males, the duration of burying was longer in the juvenile and pubertal stages
      than in adulthood. For females, no age differences in the duration of burying
      were found. Males showed longer burying durations than females in both the
      juvenile and pubertal stages. For both sexes, the highest duration of digging was
      found in the juvenile stage, and females showed longer durations of digging than
      males. Both male and female rats isolated during the juvenile stage, from 26 to
      40 days of age, showed smaller durations of burying behavior compared to pair
      reared rats. This effect of juvenile isolation was maintained among both adult
      males and females even when they were returned to pair rearing after isolation.
      Isolation during adulthood, from 66 to 80 days of age, increased burying behavior
      in males, but decreased it in females. The durations of digging, stretch-attend
      postures, and crouch/freezing were not affected by isolation. The decrease in
      defensive burying and its increase resulting from isolation in adult male rats,
      suggest that the emergence of adult-like social relationships in males suppressed
      the duration of burying. Male and female rats isolated during the juvenile stage
      maintained lower levels of burying, suggesting that social experience as
      juveniles is important for the emergence of defensive burying behavior.

PMID- 17441005
TI  - Empathy and conflict resolution in friendship relations among adolescents.
AB  - The present study addressed empathy's role in conflict resolution within the
      context of adolescent same-sex friendship relations. Self-report questionnaires
      were used to assess dispositional affective empathy and conflict resolution
      styles (problem solving, conflict engagement, withdrawal and compliance). The
      data of 307 adolescents (149 boys, 158 girls) were included in a multigroup path
      analysis with sex as a moderator variable. In agreement with the hypothesis that
      higher levels of dispositional empathy are associated with more successful
      conflict management, dispositional affective empathy was found to be positively
      linked to problem solving and negatively linked to conflict engagement among
      adolescent boys and girls. Dispositional affective empathy was not related to the
      two more passive strategies (withdrawal and compliance). Sex differences were
      demonstrated in empathic tendencies, with girls being more empathic than boys.
      Sex differences were also established in conflict resolution strategies, with
      girls using problem solving, withdrawal and compliance more frequently than boys.
      Both sexes scored equally low on conflict engagement, however, and were found to
      prefer problem solving to all other conflict resolution strategies. Findings are
      discussed in terms of previous research on empathy and conflict resolution.

PMID- 17441006
TI  - Civic community and violent behavior in Italy.
AB  - The aim of this study was to examine to what extent community characteristics
      counterbalance propensities towards homicide and robbery. Data were obtained for
      each of the 95 Italian provinces on homicide rate and robbery rate from 1992 to
      1995. Multiple regressions were used to predict these homicide and robbery rates
      from a measure of civic engagement (Civicness) assessed during the same period,
      and from other socioeconomic variables: unemployment, family break up, and
      geographical characteristics. The predictors explained 77% of the variance among
      the Italian provinces for robbery, and 61% of the variance for homicide. The
      predictive patterns were somewhat different for homicide and robbery, but in each
      case civicness interacted with territorial variables. In the case of homicide,
      civicness had a preventive impact only in the southern provinces. For robbery,
      the protective impact was limited to provinces which were urbanized and had large
      metropolitan areas.

PMID- 17441007
TI  - Officer attitudes towards adult male prisoners who self-harm: development of an
      attitudinal measure and investigation of sex differences.
AB  - PURPOSE: The aim of the current study was to explore attitudes towards self-harm
      in a sample of prison officers, with subsidiary aims of assessing if these
      attitudes alter as a function of the prisoner's behavior and the sex of the
      participant. METHOD: One hundred and sixty-two officers (100 men and 62 women)
      completed a general measure of their attitudes towards prisoners and one designed
      to assess Attitudes towards Prisoners who Self-Harm (APSH). Participants rated
      their perceptions of two adult male prisoners depicted in vignettes. The
      vignettes depicted identical types of self-harm but varied the behavioral
      characteristics of the prisoners involved, with one depicted as "well-behaved"
      and the other as "disruptive". RESULTS: Women were more likely than men to report
      positive attitudes towards self-harm and in particular were less likely than men
      to endorse negative myths regarding self-harm. The prisoner depicted as
      "disruptive" invoked increased negative attitudes than the "well-behaved"
      prisoner. This finding was consistent across sex. CONCLUSION: The current study
      indicates that APSH are comprised of a number of components that were influenced
      by the sex of the participant and the behavioral characteristics of the prisoners
      depicted. The implications of these findings to practice are discussed.

PMID- 17441008
TI  - Applying the concept of lifestyle in association with aggression and violence in
      Greek cohabitating couples.
AB  - The current study investigated the role of lifestyle as a significant factor
      related to the aggression and violence between cohabitating partners. Based on
      previous research, lifestyle was defined as a special reflection of socialization
      into society and working life, where different lifestyles should also be able to
      produce different patterns of socialization into people's roles as partners. It
      was found that gender and years of cohabitating were significantly related to
      Emotional aggression and Sexual violence; lifestyle patterns were associated with
      specific forms of violence. More specifically, the lifestyles of Pleasure &
      Elegance and the one of Culture-Intellectualism were found to promote Emotional
      aggression. Also, the lifestyle of Yuppies/Workaholic and that of Physical
      activities stimulated the appearance of Sexual violence between partners.
      Moreover, individuals with Tradition-Religiousness lifestyle were more likely to
      show lower levels of Physical & Sexual violence while the adherents of the
      Substance abuse lifestyle pattern appeared to have an inclination towards
      Physical & Sexual Violence. Finally, the occurrence of one form of violent
      behaviour was likely to be related to the other forms of violent behaviour.

PMID- 17441009
TI  - Insight into illness and adherence to psychotropic medications are separately
      associated with violence severity in a forensic sample.
AB  - Violence towards others by a minority of psychotic individuals is a significant
      public health concern. The severity of this other-directed violence (ODV) in the
      community may be influenced by insight into illness and adherence to psychotropic
      medications; however, few studies have tested these associations. Sixty male
      psychotic inpatients, legally detained at a forensic unit in New York City, were
      assessed with semi-structured interviews, supplemented with information from
      hospital and official records, family members and the treating clinician. Results
      indicated that in this unique sample of detained persons with psychotic
      disorders; (1) increase in the severity of community violence is associated with
      medication non-adherence, all dimensions of poor insight into illness, and
      several previously reported covariates such as substance use comorbidity; (2) no
      relationship was found between insight and adherence in this particular sample;
      (3) multivariate analyses showed that select covariates, along with medication
      adherence, and select insight domains predicted a total of 73% of the magnitude
      of ODV behavior in this sample. Overall, medication non-adherence explained a
      large amount of how violently participants behaved toward others. Since non
      adherence was independent of poor insight, it may be more worthwhile for
      clinicians to develop treatment strategies to target medication adherence without
      directly addressing an elusive target such as insight into illness. Treatment
      addressing medication adherence needs to concomitantly target substance use
      behaviors since the latter was responsible for a substantial increase in ODV.

PMID- 17441010
TI  - Gender differences in aggressive behavior at admission to a psychiatric hospital.
AB  - As aggressive behavior has a negative impact in general psychiatry, its influence
      specifically from a gender-related point of view in an in-patient population of a
      psychiatric clinic was assessed at the time of admission. A group of 521
      successively admitted psychiatric in-patients was investigated at admission with
      the help of the "Social Dysfunction and Aggression Scale". A slightly higher
      frequency and intensity of "verbal aggressive behavior" was observed in males.
      Within the other categories of aggressive behavior ("tension", "physical violence
      to things", and "assaults"), however, the percentages and intensities of gender
      related aggressive behavior did not differ significantly. Furthermore, under the
      covarying impact of various psychiatric diagnoses, the gender-related differences
      concerning the intensity of "verbal aggressive behavior" disappeared. When
      comparing male and female subgroups, it was notable that male schizophrenic
      patients were younger than female patients when displaying comparable risks of
      showing at least one kind of aggressive behavior. In addition, in the female
      subgroup, "self-injurious behavior" was more strongly correlated to the category
      "tension" than in the male subgroup. Although there are some methodological
      shortcomings, the present results show that there are small qualitative
      differences in gender-related aggressive behavior in addition to minimal
      quantitative differences in the frequency and intensity of "verbal aggressive
      behavior" at admission.

PMID- 17441011
TI  - Predicting sexual aggression: the role of pornography in the context of general
      and specific risk factors.
AB  - The main focus of the present study was to examine the unique contribution (if
      any) of pornography consumption to men's sexually aggressive behavior. Even after
      controlling for the contributions of risk factors associated with general
      antisocial behavior and those used in Confluence Model research as specific
      predictors of sexual aggression, we found that high pornography consumption added
      significantly to the prediction of sexual aggression. Further analyses revealed
      that the predictive utility of pornography was due to its discriminative ability
      only among men classified (based on their other risk characteristics) at
      relatively high risk for sexual aggression. Other analyses indicated that the
      specific risk factors accounted for more variance in sexual aggression than the
      general risk factors and mediated the association between the general risk
      factors and sexual aggression. We illustrate the potential application of the
      findings for risk assessment using a classification tree.

PMID- 17441012
TI  - Changes in attitudes towards war and violence after September 11, 2001.
AB  - Two inter-related studies examined the effect of the September 11, 2001,
      terrorist attacks on attitudes towards war and violence. A three-wave between
      subjects analysis revealed that attitudes towards war became more positive after
      September 11, 2001 and remained high over a year afterwards. Self-reported trait
      physical aggression also rose after September 11. Attitudes towards penal code
      violence (PCV) became more positive immediately after September 11, but were
      somewhat reduced a year afterward. A two-wave within subjects study revealed that
      war attitudes became even more positive at 2 months post-September 11. Attitudes
      towards PCV became less positive during this time period, but only for women.
      Other aggression-related attitudes were not affected in either study. These
      studies demonstrate that a large-scale event can change attitudes, but those
      attitudes must be directly relevant to the event.

PMID- 17441013
TI  - Self-esteem, academic self-concept, and aggression at school.
AB  - The present study explores the relation between academic self-concept, self
      esteem, and aggression at school. Longitudinal data from a racially diverse
      sample of middle-school students were analyzed to explore how academic self
      concept influenced the likelihood of aggressing at school and whether high self
      concept exerted a different pattern of influence when threatened. Data include
      self-reported academic self-concept, school-reported academic performance, and
      parent-reported school discipline. Results suggest that, in general, students
      with low self-concept in achievement domains are more likely to aggress at school
      than those with high self-concept. However, there is a small sample of youth who,
      when they receive contradictory information that threatens their reported self
      concept, do aggress. Global self-esteem was not found to be predictive of
      aggression. These results are discussed in the context of recent debates on
      whether self-esteem is a predictor of aggression and the use of a more proximal
      vs. general self-measure in examining the self-esteem and aggression relation.

PMID- 17441014
TI  - Anxiety sensitivity and retaliatory aggressive behavior in research volunteers.
AB  - An important focus of recent aggression research has been to identify personality
      variables that influence the expression of aggression. One such variable may be
      anxiety sensitivity (AS). Individuals high in AS fear unpleasant anxiety-related
      physiological sensations and perhaps physiological arousal in general.
      Accordingly, people high in AS are motivated to avoid situations that produce
      these sensations. With respect to aggressive encounters, an intense attack by an
      opponent involves significant physiological arousal. High anxiety-sensitive
      individuals may therefore attempt to decrease the intensity of the interaction by
      responding in a non-aggressive or conciliatory manner. To test this possibility,
      112 community volunteers completed a measure of AS and a well-validated
      laboratory task designed to assess aggressive behavior. As predicted, an inverse
      relation between AS and extreme aggressive responding was found. Specifically, as
      AS increases, retaliatory aggression is less likely after intense attack by an
      opponent.

PMID- 17441015
TI  - Bullies and victims in rural African American youth: behavioral characteristics
      and social network placement.
AB  - Bullying and victimization are serious problems for youth of many ages and from a
      variety of backgrounds. These behaviors have not, however, been widely studied in
      rural minorities. The current work examined behavioral and social correlates of
      bullying and victimization in a sample of rural African American youth. Incidence
      rates of bullying, victimization, and aggressive victimization parallel those in
      other populations. Bullies were rated as aggressive, hyperactive, and
      manipulative. Bullies and victims were both sociometrically rejected, but while
      victims were on the margin of the social network, bullies were integrated in
      their groups. Bullies' associations were heterogeneous: they belonged to both
      aggressive and non-aggressive and popular and unpopular groups. They also were
      highly likely to be leaders of their groups.

PMID- 17441016
TI  - The inter-relations of mother and father attachment, self-esteem and aggression
      during late adolescence.
AB  - This study examined three models depicting the relations between mother and
      father attachment, self-esteem and aggression. A total of 385 participants (173
      males and 212 females), aged from 18 to 20 years, completed self-rating
      questionnaires covering mother and father attachment, self-esteem and aggression.
      Results showed that self-esteem had additive and mediation effects on both the
      father attachment-aggression and mother attachment-aggression relationships, and
      also moderated the mother attachment-aggression relation. These findings are
      discussed in terms of different models for the inter-relations of mother and
      father attachment, self-esteem and aggression in late adolescence.

PMID- 17441017
TI  - Aggression, conflict resolution, popularity, and attitude to school in Russian
      adolescents.
AB  - The objective of the present study was to examine the effects of aggression and
      conflict-managing skills on popularity and attitude to school in Russian
      adolescents. Three types of aggression (physical, verbal, and indirect),
      constructive conflict resolution, third-party intervention, withdrawal, and
      victimization were examined using the Peer-Estimated Conflict Behavior (PECOBE)
      inventory [Bjorkquist and Osterman, 1998]. Also, all respondents rated peer and
      self-popularity with same-sex classmates and personal attitude to school. The
      sample consisted of 212 Russian adolescents (101 boys, 111 girls) aged between 11
      and 15 years. The findings attest to significant sex differences in aggression
      and conflict resolution patterns. Boys scored higher on physical and verbal
      aggression, and girls on indirect aggression. Girls were socially more skillful
      than boys in the use of peaceful means of conflict resolution (they scored higher
      on constructive conflict resolution and third-party intervention). The
      attributional discrepancy index (ADI) scores were negative for all three types of
      aggression in both sexes. Verbal aggression is apparently more condemned in boys
      than in girls. ADI scores were positive for constructive conflict resolution and
      third-party intervention in both genders, being higher in boys. In girls, verbal
      aggression was positively correlated with popularity. In both sexes, popularity
      showed a positive correlation with constructive conflict resolution and third
      party intervention, and a negative correlation with withdrawal and victimization.
      Boys who liked school were popular with same-sex peers and scored higher on
      constructive conflict resolution. Girls who liked school were less aggressive
      according to peer rating. They also rated higher on conflict resolution and third
      party intervention. Physical aggression was related to age. The results are
      discussed in a cross-cultural perspective.

PMID- 17441018
TI  - Network on Advanced Micro-Technologies for Microsurgery.

PMID- 17441019
TI  - Robotic applications in abdominal surgery: their limitations and future
      developments.
AB  - BACKGROUND: In the past 20 years, the technical aspects of abdominal surgery have
      changed dramatically. Operations are now routinely performed by laparoscopic
      techniques utilizing small abdominal incisions, with less patient discomfort,
      earlier recovery, improved cosmesis, and in many cases reduced economic burden on
      the healthcare provider. These benefits have largely been seen in the application
      of laparoscopic techniques to relatively straightforward procedures. It is not
      clear whether the same benefits carry through to more complex abdominal
      operations, which are more technically demanding and for which current
      laparoscopic instrumentation is less well adapted. The aim of surgical robotics
      is to address these problems and allow the advantages of minimal access surgery
      to be seen in a greater range of operations. METHODS: A literature search was
      performed to ascertain the current state of the art in surgical robotics for the
      abdomen, and the technologies emerging within this field. The reference lists of
      the sourced articles were also searched for further relevant papers. RESULTS:
      Currently available robotic devices for abdominal surgery are limited to large,
      costly 'slave-master' or telemanipulator systems, such as the da Vinci (Intuitive
      Surgical, Sunny Vale, CA). In addition to their size and expense, these systems
      share the same limitation, by virtue of the fulcrum effect on instrument
      manipulation inherent in the use of ports by which external instruments gain
      access to the abdominal cavity. In order to overcome these limitations several
      smaller telemanipulator systems are being developed, and progress towards freely
      mobile intracorporeal devices is being made. CONCLUSIONS: While current robotic
      systems have considerable advantages over conventional laparoscopic techniques,
      they are not without limitations. Miniaturisation of robotic components and
      systems is feasible and necessary to allow minimally invasive techniques to reach
      full potential. The ultimate extrapolation of this progress is the development of
      intracorporeal robotics, the feasibility of which has been demonstrated.

PMID- 17441020
TI  - Towards intra-operative computerized planning of prostate cryosurgery.
AB  - BACKGROUND: As part of ongoing efforts to develop computerized planning tools for
      cryosurgery, the current study provides a comparison between two recently
      developed methods for planning, known as bubble packing and force-field analogy.
      METHODS: For the purpose of comparison, four 3D prostate models were
      reconstructed from ultrasound imaging. The quality of planning for each method
      was evaluated based on bioheat transfer simulations. RESULTS: Both methods are
      shown to be robust planning tools in 3D. Typical results show at least 75% of the
      target region volume having temperatures below a target temperature isotherm for
      planning. While the force-field analogy method yields superior planning results,
      it comes at the expense of an order of magnitude longer run time, with only
      moderate improvement. CONCLUSIONS: Due to time constraints in a clinical setup,
      bubble packing alone may be considered adequate for computerized planning.
      Furthermore, only bubble packing is demonstrated to be adequate for intra
      operative planning.

PMID- 17441021
TI  - Robotic pyeloplasty: a critical appraisal.
AB  - BACKGROUND: Laparoscopic pyeolplasty has become a minimally invasive alternative
      to open pyeloplasty. Due to technical concerns with intracorporeal suturing,
      robotic pyeloplasty has become an emerging alternative. METHODS: The literature
      was reviewed for reports and outcomes on robotic pyeloplasty. RESULTS: Reports of
      robotic pyeloplasty are increasing, and outcomes appear excellent. CONCLUSIONS:
      Robotic pyeloplasty is feasible with excellent outcomes. Challenges remain in
      making the procedure cost effective.

PMID- 17441022
TI  - The complexity of litigation associated with robotic surgery and cybersurgery.
AB  - Litigation after cybersurgery, i.e. remote robotic surgery, will be complex. In
      addition to being able to sue physicians and hospitals, patients who sustain an
      adverse outcome after cybersurgery will have the potential to sue the robotic
      manufacturer and the telecommunications company. Moreover, cybersurgery
      litigation will involve laws that are generally unfamiliar to healthcare
      providers. Accordingly, this article examines a lawsuit involving a robotic
      surgical instrument as a model to suggest where liability traps may arise during
      the delivery of cybersurgery.

PMID- 17441023
TI  - Developing technology for surgery in the UK: a multidisciplinary meeting of
      engineers and surgeons.
AB  - There is an increasing necessity for surgeons and engineers to work together in
      order to target future technological developments at clinical need and cost
      effectiveness. This is a report of two linked meetings with these objectives,
      held at the Institute of Mechanical Engineers, London, UK. The two meetings were
      organized by the same faculty members and held on consecutive days. Delegates
      included surgeons, academic mechanical engineers, researchers and industrial
      representatives. The programme was made up of varied presentations by surgeons
      and engineers as well as open discussion of the topics covered. Delegates were
      updated on the current state of surgical robotics in the UK in four surgical
      specialties; urology, neurosurgery, orthopaedics and ENT. This included clinical
      and experimental evidence, together with discussion of future advances. Minimally
      invasive surgery, real-time imaging and the development of more compact and cost
      effective surgical robots were identified as key areas for future research.

PMID- 17441024
TI  - Robot assisted laparoscopic pyeloplasty: a review of the current status.
AB  - BACKGROUND: Over the last decade minimally invasive endourologic and laparoscopic
      techniques have become the first line therapies for primary UPJ obstruction.
      Robotic assisted laparoscopic pyeloplasty for the correction of ureteropelvic
      junction has achieved outcomes comparable to those of open and laparoscopic
      techniques. We present a comprehensive review of the current literature of
      robotic assisted pyeloplasty. METHODS: We performed a systemic review of all the
      current literature examining demographic data, intra operative parameters and
      post-operative outcomes. RESULTS: In most published series in the literature, the
      operative time ranges from 122 to 300 minutes and the operative time ranges from
      27 to 77 ml. Most series considers subjective improvement in the symptoms and
      improved drainage on post-operative diuretic renal scan as the measures of
      success. The reported success rates vary from 89 to 100%. CONCLUSION: Robotic
      pyeloplasty is a feasible alternative to laparoscopic pyeloplasty. Short-term
      results indicate equivalent outcomes with the laparoscopic procedure. Long-term
      studies are still needed to compare robotic and open pyeloplasty outcomes, and to
      define the role of robotic pyeloplasty in a cost prohibitive health care system.

PMID- 17441025
TI  - Robot-assisted minimally invasive lung brachytherapy.
AB  - BACKGROUND: This paper presents a novel alternative for the treatment of lung
      cancer. The method consists of accessing the lung through small incisions in a
      minimally invasive manner in order to insert radioactive seeds directly into the
      lung using a robotic surgical system. METHODS: An experimental test-bed to
      evaluate the feasibility of this approach has been developed. It consists of two
      surgical robotic systems, a device specifically designed to robotically implant
      radioactive seeds, needle tracking software, ultrasound imaging, electromagnetic
      tracking, and a surgical box that mimics a patient's thorax. A detailed
      comparison has been performed between currently available access options and
      robot-assisted minimally invasive access. RESULTS: The results show insignificant
      differences in accuracy between the methods, with the exception of a significant
      improvement when electromagnetic (EM) guidance was added to the non-robotic
      techniques. The navigation system reduced the number of attempts for all seed
      delivery methods. Significant reductions in time were achieved in the minimally
      invasive procedures by the addition of EM guidance. CONCLUSIONS: The performance
      achieved when using robotic systems and image guidance for minimally-invasive
      brachytherapy is clinically comparable to that achieved in an open surgery
      procedure, while reducing the invasiveness of the procedure, improving ergonomic
      conditions for the clinician and reducing radiation exposure.

PMID- 17441026
TI  - Autonomous catheter insertion system using magnetic motion capture sensor for
      endovascular surgery.
AB  - BACKGROUND: In order to reduce fluoroscope usage in endovascular surgery, there
      is a need to develop autonomous catheter insertion systems. METHODS: We propose a
      system for tracking the position and speed of a catheter using a magnetic motion
      capture sensor to provide feedback to a catheter-driving mechanism, to perform
      autonomous catheter insertion in major vasculature. Catheter insertion speed
      control and path reconstruction experiments were performed with the system inside
      a silicone model of major vasculature to simulate surgery. RESULTS: The system
      controlled the catheter for speeds of 6.14 mm/s and reproduced a two-dimensional
      path inside the silicone blood vessel phantom with less than 7 mm of error.
      CONCLUSIONS: We found that error in speed control rises as a result of friction
      between the catheter and the model wall. Path reconstruction error depends on the
      model's cross-sectional diameter, the properties of the catheter insertion
      mechanism, the magnetic sensor and the system guidance technique.

PMID- 17441027
TI  - A novel computer-assisted technique for pedicle screw insertion.
AB  - BACKGROUND: Commercially available systems for computer-assisted pedicle screw
      placement are prohibitively expensive, even in advanced countries. The advantage
      of the great accuracy of computer-assisted systems for pedicle screw insertion
      makes them highly desirable and essential for current spinal surgeries. METHODS:
      We have tried to develop a new software for pedicle screw placement, based on
      paired point matching. RESULTS: The newly developed software is much less
      expensive and is an excellent educational tool. Its accuracy has been established
      by a cadaveric study, described in this paper. CONCLUSIONS: The cadaveric study
      supports the view that computer-assisted pedicle screw fixation using the newly
      developed software is superior to the conventional fluoroscopic method,
      especially with regard to the thoracic spine, where a higher degree of accuracy
      is needed. Further clinical studies are planned and the software needs further
      refinement for complex clinical situations.

PMID- 17441028
TI  - The accuracy of computer-assisted surgical planning in soft tissue prediction
      following orthognathic surgery.
AB  - BACKGROUND: The purpose of the present study was to evaluate the accuracy of a
      computer-assisted imaging system in predicting the soft tissue response following
      orthognathic surgery. METHODS: The study sample consisted of 11 adult patients
      with a mean age of 23.5 years. The preoperative and postoperative lateral
      cephalograms were obtained after orthodontic preparation and immediately before
      surgery and at least 1 year after surgery. The computer-generated soft tissue
      image and the actual surgical outcome were compared to evaluate the accuracy of
      the imaging system. RESULTS: In the sagittal plane, the tip of nose was the most
      accurate site and the largest difference was shown in the upper lip. The lower
      lip was noted to be the least accurate and the subnasale the most accurate region
      in the vertical plane. Predictions were found to be more accurate for the
      sagittal plane when compared with those for the vertical plane. CONCLUSIONS:
      Computer-assisted visual treatment objectives was proved to be satisfactory in
      predicting the soft tissue outcome following orthognathic surgery.

PMID- 17441029
TI  - Experiences with an application of industrial robotics for accurate patient
      positioning in proton radiotherapy.
AB  - BACKGROUND: Protons beams deliver targeted radiation doses with greater precision
      than is possible with electrons or megavoltage X-ray photons, but to retain this
      advantage, patient positioning systems at proton clinics must meet tighter
      accuracy requirements. For this and other reasons, robots were incorporated into
      the treatment room systems at MPRI. METHODS: The Midwest Proton Radiotherapy
      Institute (MPRI) is the first radiotherapy facility in the United States to use
      commercial robots with six degrees of freedom for patient positioning, rather
      than a traditional bed with four degrees of freedom. RESULTS: This paper outlines
      the ways in which robots are used at MPRI and attempts to distil insights from
      the experience of treating over 200 radiotherapy patients with a robotic system
      from February 2004 to late 2006. CONCLUSIONS: The system has performed well, and
      with great reliability, but there is room for future improvement, especially in
      ease of use and in reducing the time to get patients into position.

PMID- 17441030
TI  - A prototype biosensor-integrated image-guided surgery system.
AB  - BACKGROUND: In this study we investigated the integration of a Raman spectroscopy
      based biosensor with an image-guided surgery system. Such a system would provide
      a surgeon with both a diagnosis of the tissue being analysed (e.g. cancer) and
      localization information displayed within an imaging modality of choice. This
      type of mutual and registered information could lead to faster diagnoses and
      enable more accurate tissue resections. METHODS: A test bed consisting of a
      portable Raman probe attached to a passively articulated mechanical arm was used
      to scan and classify objects within a phantom skull. RESULTS: The prototype
      system was successfully able to track the Raman probe, classify objects within
      the phantom skull, and display the classifications on medical imaging data within
      a virtual reality environment. CONCLUSION: We discuss the implementation of the
      integrated system, its accuracy and improvements to the system that will enhance
      its usefulness and further the field of sensor-based computer-assisted surgery.

PMID- 17441035
TI  - Multiphase organic synthesis in microchannel reactors.
AB  - "Miniaturization" is one of the most important aspects in today's technology.
      Organic chemistry is no exception. The search for highly effective, controllable,
      environmentally friendly methods for preparing products is of prime importance.
      The development of multiphase organic reactions in microchannel reactors has
      gained significant importance in recent years to allow novel reactivity, and has
      led to many fruitful results that are not attainable in conventional reactors.
      This Focus Review aims to shed light on how effectively multiphase organic
      reactions can be conducted with microchannel reactors by providing examples of
      recent remarkable studies, which have been grouped on the basis of the phases
      involved.

PMID- 17441036
TI  - Polymerization in coordination nanospaces.
AB  - Inspired by elegant polymerizations in biological systems, polymer synthesis in
      confined artificial nanospaces is a key challenge in the control of polymer
      structures and the design of well-defined nanostructures. In this regard, porous
      coordination polymers (PCPs) have a wide range of advantages, such as regular
      channel structures, controllable pore size, dynamic and flexible pores, and
      unique surface potentials and functionality, which can be utilized for precisely
      controlled polymerization and polymer arrangement. This Focus Review describes
      recent progress in polymerization in the nanochannels of PCPs and demonstrates
      why this polymerization system is so attractive and promising, from the
      viewpoints of three essential polymerization processes in PCPs, that is, monomer
      arrangement, polymerization methods, and control of polymer structure.

PMID- 17441037
TI  - Convergent/divergent synthesis and photophysical studies of alternating benzene
      furan oligoaryls from substituted propargylic dithioacetals.
AB  - A range of oligoaryls that contain alternating benzene-furan rings is synthesized
      by a rapid convergent/divergent method from the annulation of a propargylic
      dithioacetal and an aldehyde with a propargylic dithioacetal moiety as a
      substituent. These oligomers are fairly soluble in a range of organic solvents
      and can be easily purified by reprecipitation. The substituents on the furan
      rings can be varied according to the substituents in the starting propargylic
      dithioacetals. This route provides a useful procedure for the synthesis of
      alternating benzene-furan oligomers without repeated units. These furan
      containing oligoaryls are highly fluorescent in the visible region and are
      electrochemically active. The band gaps of these oligomers appear to be less
      sensitive towards changes in conjugation length than those of oligofurans.

PMID- 17441038
TI  - Ultrafast electron diffraction: structural dynamics of molecular rearrangement in
      the NO release from nitrobenzene.
AB  - Nitro compounds release NO, NO2, and other species, but neither the structures
      during the reactions nor the time scales are known. Ultrafast electron
      diffraction (UED) allowed the study of the NO release from nitrobenzene, and the
      molecular pathways and the structures of the transient species were identified.
      It was observed, in contrast to previous inferences, that nitric oxide and
      phenoxyl radicals are formed dominantly and that the time scale of formation is
      8.8+/-2.2 ps. The structure of the phenoxyl radical was determined for the first
      time, and found to be quinoid-like. The mechanism proposed involves a repulsive
      triplet state, following intramolecular rearrangement. This efficient generation
      of NO may have important implications for the control of by-products in drug
      delivery and other applications.

PMID- 17441039
TI  - Facile synthesis of oligosaccharide probes for the analysis of protein
      carbohydrate interactions.
AB  - A strategy for facile oligosaccharide synthesis is described. It obviates
      chromatographic separation of intermediates and enables the isolation of desired
      oligomers with capture-release purification and reverse-phase silica-gel
      cartridge separation. As an example, preparation of monoglucosylated
      mannotetraose (Glc alpha1-->3Man alpha1-->2Man1alpha-->2Man1alpha-->3Man beta)
      was conducted. After sequential glycosylation, capture-release purification with
      Cys-resin, global deprotection, and reverse-phase silica-gel cartridge
      separation, the target pentasaccharide was isolated, while isolation of shorter
      oligomers that lack nonreducing-end residues (Man alpha1-->2Man1alpha-
      >2Man1alpha-->3Man beta, Man1alpha-->2Man1alpha-->3Man beta, Man1alpha-->3Man
      beta) was also achieved. These products were connected to a thiol-containing
      linker and immobilized on Au-coated chips. Their affinity to recombinant
      calreticulin was evaluated by quartz-crystal microbalance.

PMID- 17441040
TI  - Countercation transport modeled by porous spherical molybdenum oxide based
      nanocapsules.
AB  - Porous nanosized polyoxomolybdate capsule anions of composition
      [{Mo(VI)(Mo(VI)5O21)(H2O)6}12(linker)30]n-, where (linker)30 is {Mo(V)2O4(SO4)}30
      (n = 72) (1 a) or {Mo(V)2O4(SO4)}24{Mo(V)2O4(CH3COO)}6 (n = 64) (2 a), model the
      (competitive) cellular transmembrane transport of Li+, Na+, K+, and Ca2+ ions
      along ion channels. According to X-ray crystallography and 7Li and 23Na NMR
      spectroscopy, Li+ and Na+, the counterions for 1 a and 2 a, respectively, occupy
      internal sites of the capsule. This study of the counterion transport phenomenon
      shows that, while Li+ ions can be replaced to a large extent by Na+ and K+ ions
      and completely by Ca2+ ions added to a solution of 1 a, external Li+ ions do not
      replace the incorporated Na+ ions of 2 a in an analogous experiment. In this
      context, related properties of the capsules and especially of their flexible
      channels, in connection with the complex pathways of cation uptake, are discussed
      briefly. The relevance of these investigations for lithium-based therapies is
      also addressed.

PMID- 17441041
TI  - Dynamic self-assembly of an M3L6 molecular triangle and an M4L8 tetrahedron from
      naked Pd(II) ions and bis(3-pyridyl)-substituted arenes.
AB  - The pyridine-appended nonchelating bidentate ligands 1,4-bis(3-pyridyl)benzene
      (1) and 4,4'-bis(3-pyridyl) biphenyl (2) were complexed with a naked Pd(II) ion
      for the construction of molecular cage compounds. Prior to these experiments, the
      complexation of the ligands with cis-[Pd(en)(NO3)2] was also examined, because
      self-assemblies from the cis-protected Pd(II) ion were expected to be simple
      motifs that constitute the assemblies from naked Pd(II) ion. The structures of
      the self-assembled compounds resulting from 1 and [Pd(en)(NO3)2] depended on the
      solvent employed. In aqueous solution, an M2L2 trenchlike compound was obtained.
      In dimethyl sulfoxide, however, a mixture of the M2L2 trench and an M3L3
      macrocycle was found in equilibrium, the dynamic nature of which was confirmed by
      the concentration-dependent nature of the species. At higher concentration, an
      M4L4 macrocycle was mostly observed. The complexation of 1 with naked Pd(II) ions
      was expected to produce novel structures that are combinations of the M(n)L(n)
      type frameworks. A peculiar tetrahedral M4L8 assembly was obtained quantitatively
      from 1 and Pd(NO3)2, rather than the smallest possible M3L6 double-walled
      triangle. Interestingly, the use of Pd(CF3SO3)2 resulted in the sole formation of
      the latter structure. Thus, the anion is important as a template in the formation
      of these assemblies. Ligand 2, which contains an extra p-phenylene unit compared
      to 1, behaved in a similar manner when treated with [Pd(en)(NO3)2], but showed
      subtle differences with naked Pd(II) ions. With Pd(NO3)2, 2 gave mostly a
      tetrahedron along with a double-walled triangle. With Pd(CF3SO3)2, this longer
      ligand formed a double-walled triangle with a negligible amount of tetrahedra. A
      single discrete assembly of a perfect tetrahedron was obtained from 2 and Pd(II)
      ions by choosing p-tosylate as a counterion.

PMID- 17441042
TI  - Preparation of nearly monodisperse nanoscale inorganic pigments.
AB  - Many different important commercial pigments have been synthesized based on the
      liquid-solid-solution (LSS) phase-transfer and separation process. Transmission
      electron microscopy (TEM) measurement results show that they are very small in
      size and have a narrow size distribution. Visible absorption spectra were taken
      to examine the very pure and brilliant colors of the pigments. They can be well
      dispersed in cyclohexane and remain non-agglomerated, even over several months.
      These nearly monodisperse nanoscale inorganic pigments may have wide applications
      in many important fields and could bring about new developments in the pigment
      industry.

PMID- 17441043
TI  - Unexpected chiroptical inversion observed for supramolecular complexes formed
      between an achiral polythiophene and ATP.
AB  - A series of supramolecular complexes between a water-soluble achiral
      polythiophene derivative (PT-1) and various nucleotides has been prepared. It was
      found that upon the introduction of adenosine diphosphate (ADP), adenosine
      triphosphate (ATP), and uridine triphosphate (UTP) into aqueous solutions of
      achiral PT-1, which has a random-coiled conformation, chiral supramolecular pi
      stacked aggregates of PT-1 can be constructed. These complexes exhibit an unique
      split-type induced circular dichroism (ICD) in the pi-pi* transition region of
      the main chain. In particular, it was found that the Cotton effect of the chiral
      supramolecular PT-1/ATP aggregates reveals a dramatic inversion of chirality with
      a change in the concentration of ATP, which has not been previously observed in
      chiral macromolecular complexes. On the basis of extensive investigations
      performed with UV/Vis spectroscopy, CD spectroscopy, TEM, AFM, and dynamic light
      scattering (DLS), a possible mechanism for the formation of chiral
      superstructures of PT-1 and chiroptical inversion induced by changes in ATP
      concentration is proposed.

PMID- 17441044
TI  - Mechanism of asymmetric hydrogenation of acetophenone catalyzed by chiral eta(6)
      arene-N-tosylethylenediamine-ruthenium(II) complexes.
AB  - Chiral arene-N-tosylethylenediamine-Ru(II) complexes can be made to effect both
      asymmetric transfer hydrogenation and asymmetric hydrogenation of simple ketones
      through a slight functional modification and by switching reaction conditions.
      [Ru(OSO2CF3){(S,S)-TsNCH(C6H5)CH(C6H5)NH2}(eta(6)-p-cymene)] catalyzes the
      asymmetric hydrogenation of acetophenone in methanol to afford (S)-1
      phenylethanol with 96% ee in 100% yield. Like the transfer hydrogenation
      catalyzed by similar Ru catalysts with basic 2-propanol or a formic
      acid/triethylamine mixture, this hydrogenation proceeds through a metal-ligand
      bifunctional mechanism. The reduction of the C=O function occurs via an
      intermediary 18e RuH species in its outer coordination sphere without metal
      substrate interaction. The high catalytic efficiency relies on the facile
      ionization of the Ru triflate complex in methanol. The turnover rate is dependent
      on hydrogen pressure and medium acidity and basicity. The RuCl analogue can be
      used as a precatalyst, albeit less effectively. Unlike the well-known diphosphine
      1,2-diamine-Ru(II)-catalyzed hydrogenation that proceeds in a basic alcohol, this
      reaction takes place under slightly acidic conditions, creating new opportunities
      for asymmetric hydrogenation.

PMID- 17441045
TI  - Total synthesis of (+/-)-pallavicinin and (+/-)-neopallavicinin.
AB  - Through a biomimetic pathway, (+/-)-pallavicinin and (+/-)-neopallavicinin were
      synthesized from (+/-)-Wieland-Miescher ketone via Grob fragmentation,
      intramolecular aldol cyclization, and intramolecular Michael reaction. The
      synthesis was stereocontrolled efficiently and followed the stereochemistry of
      the Wieland-Miescher ketone, and could provide opportunities for access to
      analogues of pallavicinin, neopallavicinin, and other related bioactive
      diterpenoids.

PMID- 17441046
TI  - Chiral scandium catalysts for enantioselective Michael reactions of beta
      ketoesters.
AB  - A highly enantioselective Michael reaction of beta-ketoesters with alpha,beta
      unsaturated ketones promoted by a chiral scandium catalyst has been developed. In
      the presence of Sc(OTf)3 and (S,S)-6,6'-bis(1-hydroxy-2,2'-dimethylpropyl)-2,2'
      bipyridine, the desired Michael reactions proceeded smoothly in dichloroethane at
      40 degrees C to afford the corresponding adducts in good to high yields with
      excellent enantioselectivities in most cases. It was found in this reaction that
      a lower concentration of the reaction mixture was key to attaining high
      enantioselectivities.

PMID- 17441047
TI  - An efficient total synthesis of optically active tetrodotoxin from
      levoglucosenone.
AB  - Tetrodotoxin, a toxic principal of puffer-fish poisoning, is one of the most
      famous marine natural products, and has been known as a formidable synthetic
      target in synthesis owing to its multifunctional structure and unusual chemical
      properties. From the perspective of supplying tetrodotoxin derivatives such as
      labeled molecules for biochemical research, we have completed our second total
      synthesis of tetrodotoxin from a synthetic intermediate for 11-deoxytetrodotoxin,
      which was previously prepared from levoglucosenone as a chiral starting material
      in this laboratory. This paper discloses the details of the total synthesis with
      special reference to significant influences on the neighboring functional groups
      found in the installation of guanidine. The established route should allow us to
      prepare the tetrodotoxin-related compounds required for biochemical studies.

PMID- 17441048
TI  - Flavin-catalyzed oxidation of amines and sulfides with molecular oxygen:
      biomimetic green oxidation.
AB  - Flavin-catalyzed green oxidation of heteroatom compounds such as sulfides and
      amines with molecular oxygen and even air in the presence of hydrazine
      monohydrate in a fluorous solvent such as 2,2,2-trifluoroethanol at room
      temperature gives the corresponding oxidation products highly efficiently and
      selectively along with water and molecular nitrogen, which are environmentally
      benign by-products. The proposed reaction mechanism is based on the kinetics,
      solvent effect, and redox properties of flavin catalysts.

PMID- 17441049
TI  - New donor-acceptor materials based on random polynorbornenes bearing pendant
      phthalocyanine and fullerene units.
AB  - New donor-acceptor materials based on a polynorbornene framework to which both
      phthalocyanine and C60 electroactive pendant units are randomly attached have
      been prepared in good yield by ring-opening-metathesis polymerization (ROMP) in
      the presence of a Grubbs catalyst. A structurally related phthalocyanine
      homopolymer was also synthesized for comparison. A remarkable fluorescence
      quenching was observed in the homopolymer and accounts for PcPc interactions
      along the polymeric framework. As expected, the fluorescence quenching increases
      in the case of the polynorbornenes containing both Pc and C60 units owing to
      photoinduced electron transfer, which was further confirmed by transient
      absorption spectroscopy. Finally, preliminary solar cell devices made of one of
      the copolymers were constructed.

PMID- 17441050
TI  - New synthetic routes to C-amino phosphorus ylides and their subsequent
      fragmentation into carbenes and phosphines.
AB  - Phosphonio-substituted aldiminium, iminium, and imidazolidinium salts are readily
      prepared by the addition of phosphines to the Alder dimer or by treatment of the
      corresponding chloroiminium salt with the phosphine/trimethylsilyl triflate
      adduct generated in situ. Reduction with either potassium metal or
      tetrakis(dimethylamino)ethylene leads to the corresponding C-amino phosphorus
      ylides. When basic phosphine fragments are used, the ylides can be isolated;
      otherwise they fragment into the carbene and phosphine. This method is limited to
      the preparation of transient carbenes, owing to the unavailability of sterically
      hindered dications, and consequently of phosphorus ylides with bulky carbon
      substituents. This difficulty is overcome by the addition of 2,4-di-tert-butyl
      ortho-quinone to readily available C-amino phosphaalkenes at low temperature.
      Provided the phosphorus atom bears either an amino or tert-butyl group, [4+1]
      cycloaddition occurs, and the resulting ylides fragment into a dioxaphospholane
      and a spectroscopically observed carbene.

PMID- 17441051
TI  - Nucleophilic activation of alkenyl and aryl boronates by a chiral Cu(I)F complex:
      catalytic enantioselective alkenylation and arylation of aldehydes.
AB  - A new method for the catalytic enantioselective alkenylation and arylation of
      aldehydes involves the activation of alkenyl and aryl boronates by a catalytic
      amount of the Cu(I)F-DTBM-segphos complex through transmetalation, generating
      novel alkenyl and aryl copper species. These reagents act as the actual
      nucleophile. A range of aldehydes can be converted into optically active
      secondary allyl alcohols or diaryl methanols with excellent enantioselectivity.
      The appropriate choice of additives, depending on the substrate, is critical to
      ensure high yields of products. These additives possibly modulate the catalyst
      turnover step from copper alkoxide intermediates generated by the addition of
      organocopper reagents to aldehydes.

PMID- 17441052
TI  - Gene delivery by aminofullerenes: structural requirements for efficient
      transfection.
AB  - A series of aminofullerenes that share a common structural motif have been
      synthesized and subjected to a systematic investigation of structure activity
      relationship regarding their ability for transient transfection and cytotoxicity.
      DNA-binding tests indicated that any water-soluble fullerene-bearing amino group
      would bind to double-stranded DNA. For these molecules to be effective
      transfection reagents, however, they require additional structural features.
      First, the molecule must be capable of producing submicrometer-sized
      fullerene/DNA aggregates that can be internalized into mammalian cells through
      endocytosis. Second, the molecule must be capable of releasing DNA as the
      aggregates are transferred into the cytoplasm. This can be achieved in at least
      two ways: by loss of the DNA-binding amino groups from the fullerene core, and by
      transformation of the amino groups to neutral groups such as amides. The
      screening experiments led us to identify the best reagent, a
      tetrapiperidinofullerene, that can be synthesized in two steps from fullerene,
      piperazine, and molecular oxygen, and that is more efficient at transfection than
      a commonly used lipid-based transfection reagent.

PMID- 17441053
TI  - Mono- and di(dimethylamino)styryl-substituted borondipyrromethene and
      borondiindomethene dyes with intense near-infrared fluorescence.
AB  - Four novel borondipyrromethene (BDP) and -diindomethene (BDI) dyes with one or
      two (dimethylamino)styryl extensions at the chromophore were synthesized and
      spectroscopically investigated. An X-ray crystal structure shows that the
      extended auxochrome is virtually planar. All dyes thus display intense red/near
      infrared (NIR) absorption and emission. The (dimethylamino)styryl group induces a
      charge-transfer character that entails bright solvatochromic fluorescence, which
      is only quenched with increasing solvent polarity according to the energy-gap
      law. The dye with an additional dimethylanilino group at the meso position of BDP
      shows a remarkable switching of lipophilicity by protonation. Two dyes with an 8
      hydroxyquinoline ligand at the meso position display quenched emission in the
      presence of Hg2+ or Al3+ owing to electron transfer from the excited BDP to the
      complexed receptor. The BDI dye presents a pH indicator with bright fluorescence
      and extremely low fluorescence anisotropy.

PMID- 17441054
TI  - A femtosecond study of excitation-wavelength dependence of solvation dynamics in
      a vesicle.
AB  - The dependence of fluorescence and solvation dynamics of coumarin 480 (C480) in a
      dimyristoyl-phosphatidylcholine (DMPC) vesicle on excitation wavelength
      (lambda(ex)) was studied with femtosecond fluorescence upconversion. The study
      revealed an ultrafast 1.5-ps component of solvation that was not detected
      earlier. C480 exhibits pronounced red-edge excitation shift (REES) by 10 nm in a
      DMPC vesicle. This is due to the microheterogeneity of the lipid vesicle. In
      lipids, the probe is distributed in different locations with varying static and
      dynamic electrostatic responses. Solvent relaxation becomes faster and the amount
      of dynamic Stokes shift decreases with increasing lambda(ex). For excitation at
      the red end (lambda(ex) = 430 nm), the solvation time was found to be 1.5 ps.
      However, for excitation at the blue end, (lambda(ex) = 390 nm), there are two
      substantially slower components of 250 and 2000 ps. It seems that for lambda(ex)
      = 390 nm, the major contribution to total emission is due to the probe (C480)
      molecules in the hydrophobic and restricted locations inside the lipid bilayer.
      Excitation at 430 nm preferentially selects the probe molecules in a highly
      mobile environment (water pool of the lipid).

PMID- 17441055
TI  - Complex of silylene with nitrogen: a combined matrix-spectroscopic and density
      functional theory study.
AB  - The quest for a new and productive route to matrix-isolated silylene 1 has led to
      the observation that the presence of nitrogen is favorable, as under such
      conditions 1 is stabilized by formation of a donor-acceptor complex 1 x N2.
      Either matrix photolysis of diazidosilane or pulsed high-vacuum flash pyrolysis
      of 1,1,1-trimethyldisilane, followed by condensation of the products with
      nitrogen at 10 K, were applied as synthetic procedures. In a similar manner,
      complex 1 x CO can be generated. The results are supported by isotopic-labeling
      studies. The structural elucidation of the new species is based on the comparison
      of experimental IR and UV/Vis spectra with data from density functional theory
      calculations.

PMID- 17441056
TI  - Highly efficient three-component synthesis of beta-lactams from N
      methylhydroxylamine, aldehydes, and phenylacetylene.
AB  - The three-component reaction of N-substituted hydroxylamines, aldehydes, and
      phenylacetylene catalyzed by CuCl/2,2'-bipyridine in the presence of NaOAc under
      neat conditions afforded the corresponding beta-lactams in good to excellent
      yields. Aromatic, heteroaromatic, and aliphatic aldehydes are tolerated in this
      reaction. The electronic effects of the aldehydes were studied for the reaction
      with N-methylhydroxylamine and N-benzylhydroxylamine. For N-methylhydroxylamine,
      electron-rich aldehydes provided higher yields than electron-deficient aldehydes,
      whereas for N-benzylhydroxylamine, no significant electronic effect was observed
      for the aldehydes.

PMID- 17441057
TI  - Design of a binaphthyl-based axially chiral amino acid as an organocatalyst for
      direct asymmetric aldol reactions.
AB  - A novel and robust binaphthyl-based amino acid was designed and successfully
      applied to the direct asymmetric aldol reaction. In some cases, this catalyst
      leads to higher yields and selectivities than the well-known proline catalyst.
      For instance, the direct asymmetric aldol reaction of acetone with 4
      nitrobenzaldehyde in the presence of the binaphthyl-based amino acid catalyst
      proceeded smoothly to give the aldol adduct in 82% yield with 95% ee. This
      catalyst was also found to catalyze effectively the reactions of cyclic or
      unsymmetrical ketones to give the corresponding aldol adducts with excellent
      diastereo- and enantioselectivities.

PMID- 17441058
TI  - Diffusion-influenced reversible trapping problem in the presence of an external
      field.
AB  - We investigate the field effect on the diffusion-influenced reversible trapping
      problem in one dimension. The exact Green function for a particle undergoing
      diffusive motion between two static reversible traps with a constant external
      field is obtained. From the Green function, we derive the various survival
      probabilities. Two types of trap distribution for the many-body problem are
      considered, the periodic and random distributions. The mean survival probability
      is obtained for the crossing-forbidden case for the two types of trap
      distribution. For the periodic distribution it decays exponentially. For the
      random trap distribution, similar to the irreversible case, there exists a
      critical field strength at which the long time asymptotic behavior undergoes a
      kinetic transition from the power law to exponential behaviors. The difference
      between equilibrium concentrations for the two types of trap distribution due to
      the fluctuation effect of trap concentration vanishes as the field strength
      increases.

PMID- 17441059
TI  - Pyrene-based dual-mode fluorescence switches and logic gates that function in
      solution and film.
AB  - A dual-mode fluorescence switch controlled by external inputs such as protons and
      metal ions is described, and each state corresponds to a specific fluorescent
      emission peak. Based on the reversible changes of the fluorescence emission of
      the switch responding to different external stimuli, the corresponding integrated
      logic gates and communication networks have been constructed in solid film or in
      solution.

PMID- 17441060
TI  - Packing modes in some mono- and disubstituted phenylpropiolic acids: repeated
      occurrence of the rare syn,anti catemer.
AB  - The catemer is an infinite one-dimensional pattern formed by the carboxylic acid
      group in crystals, and is constituted with O-H...O hydrogen bonds. The catemer is
      uncommon and may be contrasted with the ubiquitous carboxylic acid dimer, the
      favored mode of association of this functional group. Both catemers and dimers,
      however, have two O-H...O hydrogen bonds for each carboxy group, so the reasons
      for the rarity of the catemer must lie elsewhere. In this paper, we describe a
      group of around 25 phenylpropiolic acids in which the catemer is the default
      packing mode. Exceptionally, the particular catemer that is found in this family
      is of the very rare syn,anti variety. We show that a necessary ingredient in
      catemer formation is a supportive C-H...O hydrogen bond from a proximal C-H
      group, which is located on the phenyl ring, ortho to the ethynyl group, and
      suitably activated by electron withdrawing substituents. When steric factors
      become noteworthy, alternative patterns are adopted, such as the syn,syn catemer
      and, in one case, a rare cisoid dimer. When electron-donating groups, either
      through inductive effect such as methyl or through resonance such as halogens,
      are present on the phenyl ring, the dimer is formed in all but one case.
      Polymorphism seems not to be an issue in these carboxylic acids in that no
      compound would generally crystallize as both a dimer and a catemer. It may be
      concluded that a supporting interaction, in this case a C-H...O hydrogen bond, is
      the essential condition for the formation of any carboxylic acid catemer.
      Catemers are so rare because it is difficult to set up this type of supporting
      interaction in most carboxylic acids.

PMID- 17441061
TI  - Second-generation total synthesis of azaspiracids-1, -2, and -3.
AB  - The naturally occurring but scarce marine neurotoxins azaspiracids-1, -2, and -3
      have been synthesized from five key building blocks by a convergent strategy that
      involved dithiane and Stille coupling reactions. The ABCD fragments were
      constructed through a cascade reaction involving deprotection/self-assembly of
      the precursors, while the FGHI fragment was forged by a neodymium triflate
      induced cyclization. The final ring closure (ring G) was achieved, after the
      union of all fragments, through an iodoetherification reaction followed by
      reductive removal of the facilitating iodine residue. These improved, second
      generation routes confirm the absolute structures and render all three
      azaspiracids readily available for biological studies.

PMID- 17441062
TI  - Methylation of [Pt2(mu-SR)(mu-S)(PPh3)4]: en route to mixed-thiolato bridged
      complexes.
AB  - Sequential and independent alkylation of [Pt2(mu-S)2(PPh3)4] by RX followed by
      methylation with Me2SO4 led to the first successful isolation of novel diplatinum
      complexes [Pt2(mu-SR)(mu-SCH3)(PPh3)4](PF6)2 (3) (R = CH2C6H5 (a), CH2CHCH2 (b),
      C5H10CO2CH2CH3 (c), C2H4CO2CH2CH3 (d), CH2CH2CN (e), C2H4CH(O)2C2H4 (f), and
      C2H4SC6H5 (g)) with asymmetric thiolato bridges. The synthetic methodology can
      tolerate a range of electronically and sterically contrasting thiolate
      substituents with different chemical functionalities. The X-ray crystal
      structures of 3 a-c, g confirm the unusual heterodialkylation with two different
      thiolato bridging ligands in a syn-exo conformation. A secondary product [Pt2(mu
      SC2H4SC6H5)(mu-SCH3)(PPh3)3](PF6)2 (4), which arises from intramolecular
      phosphine displacement by the thio pendant at the neighboring SC2H4SC6H5 bridge,
      has been trapped and characterized. This is an unusual diplatinum complex with
      three different bridging thio ligands and three different phosphines. The
      heteroalkylation is screened in situ by ESI-MS, and the resultant spectral data
      provide a convenient guide for one-pot syntheses of {M2(SR)(SR')} from{M2S}. The
      isolation and X-ray crystal structure of a homoalkylated analogue [Pt2(mu
      SCH3)2(PPh3)4](PF6)2 (6) is included for comparison.

PMID- 17441063
TI  - Luminescent molecular copper(I) alkynyl open cubes: synthesis, structural
      characterization, electronic structure, photophysics, and photochemistry.
AB  - A novel class of tetranuclear copper(I) alkynyl complexes with an "open-cube"
      structure was synthesized. The crystal structure of [Cu4{P(p-MeC6H4)3}4(mu3
      eta(1),eta(1),eta(2)-C[triple bond]C-p-MeOC6H4)3]PF6 was determined. These
      complexes were found to display dual emission behavior. Through systematic
      comparison studies on the electronic absorption and photoluminescence properties
      of a series of [Cu4(PR3)4(mu3-eta(1),eta(1),eta(2)-C[triple bond]CR')3]+
      complexes, together with density functional theory (DFT) calculations at the
      PBE1PBE level on the model complex [Cu4(PH3)4(mu3-eta(1),eta(1),eta(2)-C[triple
      bond]C-p-MeOC6H4)3]+, the nature of their emission origins was probed. Their
      photochemical properties were also investigated by oxidative quenching
      experiments and transient absorption spectroscopy.

PMID- 17441065
TI  - Illuminating molecular processes in living cells.
AB  - Lately, scientists have explored approaches to developing fluorescent and/or
      bioluminescent indicators to pinpoint cellular processes in single living cells.
      These analytical methods have become a key technology for visualizing and
      detecting what was otherwise unseen in live cells. The target signaling included
      second messengers, protein phosphorylations, protein-protein interactions, and
      protein localizations.

PMID- 17441066
TI  - Identification of potent, selective protein kinase C inhibitors based on a
      phorbol skeleton.
AB  - The elucidation of specific functions of protein kinase C (PKC) subtypes in
      physiological processes is an important challenge for the future development of
      new drug targets. Subtype-selective PKC agonists and antagonists are useful
      biological tools for this purpose. Most of the currently used PKC modulators
      elicit their activities through binding to the ATP binding site of PKC, which
      shares many features with other kinases. PKC modulators that target the PKC
      regulatory domain are considered to be advantageous in terms of selectivity,
      because the structure of the regulatory domain is intrinsic to each PKC subtype.
      In this paper, we describe the identification of new potent and conventional PKC
      selective inhibitors that target the regulatory domain. The inhibitors contain a
      phorbol skeleton, a naturally occurring potent and selective PKC regulatory
      domain binder, with a perfluorinated alkyl group and a polyether hydrophilic
      chain on a terephthaloyl aromatic ring at the C12 position. Both of these
      substituents are essential for the potent inhibitory activity. Specifically, the
      binding affinity between PKC and the phorbol ester analogues was improved by an
      electron-deficient aromatic ring at C12. This finding cannot be explained by the
      previously proposed binding model and suggests a new binding mode between phorbol
      esters and PKC.

PMID- 17441067
TI  - Mechanism of remote conjugate addition of lithium organocuprates to
      polyconjugated carbonyl compounds.
AB  - Regioselective reaction of a lithium organocuprate (R2CuLi) and a polyconjugated
      carbonyl compound affords a remote-conjugate-addition product. This reaction
      proceeds particularly cleanly when the conjugation is terminated by a C-C triple
      bond. The reaction pathways and the origin of the regioselectivity of this class
      of transformations are explored with the aid of density functional calculations.
      The outline of the reaction pathway is as follows. An initially formed beta
      cuprio(III) enolate intermediate undergoes smooth copper migration along the
      conjugated system. This process takes place faster than reductive elimination of
      intermediary sigma/pi-allylcopper(III) species, since the latter reaction
      disrupts the conjugation in the substrate and hence is not preferred. The copper
      migration to the acetylenic terminal affords a sigma/pi-allenylcopper(III)
      intermediate, which undergoes facile and selective C-C bond forming reductive
      elimination at the terminal carbon atom. The present mechanistic framework shows
      good agreement with some pertinent experimental data, including 13C NMR chemical
      shifts and kinetic isotope effects.

PMID- 17441068
TI  - Formation, dynamic behavior, and chemical transformation of Pt complexes with a
      rotaxane-like structure.
AB  - The reaction of [Pt(CH2COMe)(Ph)(cod)] (cod = 1,5-cyclooctadiene) with
      (ArCH2NH2CH2-C6H4COOH)+ (PF6)- (Ar = 4-tBuC6H4 or 9-anthryl) in the presence of
      cyclic oligoethers such as dibenzo[24]crown-8 (DB24C8) and dicyclohexano[24]crown
      8 (DC24C8) produces {(ce)[ArCH2NH2CH2C6H4COOPt(Ph)(cod)]}+ (PF6)- (ce = DB24C8 or
      DC24C8, Ar = 4-tBuC6H4 or 9-anthryl) with interlocked structures. FABMS and NMR
      spectra of a solution of these compounds indicate that the Pt complexes with a
      secondary ammonium group and DB24C8 (or DC24C8) make up the axis and cyclic
      components, respectively. Temperature-dependent 1H NMR spectra of a solution of
      {(DB24C8)[4-tBuC6H4CH2NH2CH2-C6H4COOPt(Ph)(cod)]}+ (PF6)- ({(DB24C8)[4-H]}+ (PF6)
      ) show equilibration with free DB24C8 and the axis component. The addition of
      DB24C8 to a solution of {(DC24C8)[4-H]}+ (PF6)- causes partial exchange of the
      macrocyclic component of the interlocked molecules, giving a mixture of
      {(DC24C8)[4-H]}+ (PF6)-, {(DB24C8)[4-H]}+ (PF6)-, and free macrocyclic compounds.
      The reaction of 3,5-Me2C6H3COCl with {(DB24C8)[4-H]}+ (PF6)- affords the organic
      rotaxane {(DB24C8)(4-tBuC6H4CH2NH2CH2-C6H4COOCOC6H3Me2-3,5)}+ (PF6)- through C-O
      bond formation between the aroyl group and the carboxylate ligand of the axis
      component. The addition of 2,2'-bipyridine (bpy) to a solution of {(DB24C8)[4
      H]}+ (PF6)- induces the degradation of the interlocked structure to form a
      complex with trigonal bipyramidal coordination, [Pt(Ph)(bpy)(cod)]+ (PF6)-,
      whereas the reaction of bpy with [Pt(OCOC6H4Me-4)(Ph)(cod)] produces the square
      planar complex [Pt(OCOC6H4Me-4)(Ph)(bpy)].

PMID- 17441069
TI  - Interpenetrating coordination polymers from Cu(I) or Ag(I) and flexible ligands:
      2D polyrotaxanes and interpenetrating grids.
AB  - The reaction of [Cu(CH3CN)4]NO3 or AgNO3 with flexible ligands 1,4-bis(4
      pyridylmethyl)-2,3,5,6-tetrafluorobenzene (bpf) or 4,4'-bis(4-pyridylmethyl)
      2,2',3,3',5,5',6,6'-octafluorobiphenyl (bpfb) afforded two types of
      interpenetrating coordination polymers. The structures of [Cu2(bpf)3(NO3)2]n and
      [Ag2(bpf)3-(NO3)2]n are 2D polyrotaxane networks in which 1D polymeric chains are
      aligned in a grid. The structure of {[Cu(bpfb)2]NO3}n is a 2D grid polymer with
      two-fold parallel interpenetration.

PMID- 17441070
TI  - A dodecalanthanide wheel supported by p-tert-butylsulfonylcalix[4]arene.
AB  - A dodecaholmium wheel of [Ho12(L)6(mal)4(AcO)4(H2O)14] (1; mal = malonate) was
      synthesized by using p-tert-butylsulfonylcalix[4]arene (H4L) as a cluster-forming
      ligand. The wheel consists of three fragments of mononuclear A3-
      ([Ho(L)(mal)(H2O)]3-), trinuclear B3- ([Ho(H2O)2(mal)(Ho(L)(AcO))2]3-), and C3+
      ([Ho(H2O)2]3+), and an alternate arrangement of these fragments (A(3-)-C(3+)-B(3
      )-C(3+)-A(3-)-C(3+)-B(3-)-C(3+)-) results in a wheel structure. The longest and
      shortest diameters of the core were estimated to be 17.7562(16) and 13.6810(13)
      A, respectively, and the saddle-shaped molecule possesses a pocketlike cavity
      inside.

PMID- 17441071
TI  - Linking chiral clusters with molybdate building blocks: from homochiral helical
      supramolecular arrays to coordination helices.
AB  - The synthesis of four new oxo-centered Fe clusters (1 a-c, 2) of the form
      [Fe(III)3(mu3-O)(CH2=CHCOO)6] with acrylate as the bridging ligand gives rise to
      potentially intrinsically chiral oxo-centered {M3} trimers that show a tendency
      to spontaneously resolve upon crystallization. For instance, 1 a, [Fe(III)3(mu3
      O)(CH2=CHCOO)6-(H2O)3]+, crystallizes in the chiral space group P3(1) as a
      chloride salt. Crystallization of 1 b, [Fe3(mu3-O)(C2H3CO2)6(H2O)3]NO3 x 4.5 H2O,
      from aqueous solution followed by recrystallization from acetonitrile also gives
      rise to spontaneous resolution to yield the homochiral salt [Fe3(mu3-O)(C2H3CO2)6
      (H2O)3]NO3 x CH3CN of 1 c (space group P2(1)2(1)2(1)). Furthermore, the reaction
      of 1 a with hexamolybdate in acetonitrile gives the helical coordination polymer
      {[(Fe3(mu3-O)L6(H2O))(MoO4)-(Fe3(mu3-O)L6(H2O)2)] x 2 CH3CN x H2O}infinity 2 (L:
      H2C=CHCOO), which crystallizes in the space group P2(1). The nature of the ligand
      geometry allows the formation of atropisomers in both the discrete (1 a-c) and
      linked {Fe3} clusters (2), which is described along with a magnetic analysis of 1
      a and 2.

PMID- 17441073
TI  - Reversible full-range color control of a cholesteric liquid-crystalline film by
      using a molecular motor.
AB  - By using a chiral molecular motor as a dopant in a cholesteric liquid-crystalline
      film, fully reversible control of the reflection color of this film across the
      entire visible spectrum is possible. The large difference in helical twisting
      power between the two isomeric forms of the motor allows efficient light- and
      heat-induced switching of the helicity of the cholesteric liquid-crystal
      superstructure.

PMID- 17441072
TI  - A myoglobin functional model composed of a ferrous porphyrin and a cyclodextrin
      dimer with an imidazole linker.
AB  - A 1:1 inclusion complex (Fe(II)PImCD) of 5,10,15,20-tetrakis- (4
      sulfonatophenyl)porphinatoiron(II) (Fe(II)P) and an O-methylated beta
      cyclodextrin dimer with an imidazole linker (ImCD) was found to bind dioxygen in
      aqueous solution. The half-saturation pressure of dioxygen (P(1/2)O2) is 1.7 torr
      at 25 degrees C, which is 10 times lower than that for a previous myoglobin
      functional model (hemoCD) with a pyridine linker. Meanwhile, the half-life of
      oxygenated Fe(II)PImCD is 3 h, which is 10 times shorter than that of oxygenated
      hemoCD. The covering of the iron(II) center by a microscopic environment is
      essential for preventing autoxidation of oxygenated ferrous porphyrin, which is
      promoted by nucleophilic attack of H2O and/or nucleophiles such as inorganic
      anions. Due to structural requirements, covering of the Fe(II) center of
      Fe(II)PImCD is insufficient compared with the case of hemoCD. As a result, water
      molecules can penetrate more easily the cleft of the O2-Fe(II)PImCD complex and
      act as an autoxidation inducer. This structure also causes poorer selectivity
      against carbon monoxide (M = 1040). In contrast, the dioxygen affinity of
      Fe(II)PImCD is much higher than that of hemoCD because the imidazole moiety is a
      stronger electron donor than pyridine.

PMID- 17441074
TI  - A formal total synthesis of taxol aided by an automated synthesizer.
AB  - A 36-step synthesis was carried out in automated synthesizers to provide a
      synthetic key intermediate of taxol. A key step involved a microwave-assisted
      alkylation reaction to construct the ABC ring system from an AC precursor.
      Subsequent formation of the D ring afforded baccatin III, a well-known precursor
      of taxol.

PMID- 17441076
TI  - Transition states of binap-rhodium(I)-catalyzed asymmetric hydrogenation:
      theoretical studies on the origin of the enantioselectivity.
AB  - By using the hybrid IMOMM(B3LYP:MM3) method, we examined the binap-Rh(I)
      catalyzed oxidative-addition and insertion steps of the asymmetric hydrogenation
      of the enamide 2-acetylamino-3-phenylacrylic acid. We report a path that is
      energetically more favorable for the major enantiomer than for the minor
      enantiomer. This path follows the "lock-and-key" motif and leads to the major
      enantiomeric product via an energetically favorable binap-dihydride-Rh(III)
      enamide complex. Our theoretical results are consistent with the mechanism that
      takes place via Rh(III) dihydride formation, that is, oxidative addition of H2
      followed by enamide insertion.

PMID- 17441075
TI  - Using bioconjugated nanoparticles to monitor E. coli in a flow channel.
AB  - A simple and portable flow channel optical detection system combined with
      bioconjugated luminescent nanoparticles allows the rapid detection of single
      bacterial cells without sample enrichment. The optical system is designed to have
      single-molecule-detection capability in a microcapillary flow channel by
      decreasing the laser excitation probe volume to a few picoliters, which
      consequently results in a low background. Specific monoclonal antibodies were
      immobilized on nanoparticles to form nanoparticle-antibody conjugates. The
      bioconjugated nanoparticles bind to the target bacteria when they recognize the
      antigen on the bacterium surface, thus providing a bright luminescent signal for
      the detection of individual bacteria cells. The high sensitivity provided by the
      luminescent and photostable silica nanoparticles eliminates the need for further
      enrichment of bacteria samples and signal amplification. This flow channel
      detection system is convenient and allows the detection of single bacterial cells
      within a few minutes.

PMID- 17441077
TI  - Periodic trends in the agostic interaction in zirconium and hafnium methylidene
      hydride halide complexes.
AB  - The reactions of methyl chloride and bromide with laser-ablated Zr and Hf atoms
      during deposition in excess Ne, Ar, or Kr are investigated, and the products are
      examined by matrix IR spectroscopy and density functional theory calculations.
      The methylidene complexes, [CH2=MHX] (M = Zr and Hf, X = Cl and Br), are formed
      along with the methyl metal halide complexes, [CH3-MX]. The amounts of both types
      of complexes increase upon photolysis and in the early stages of annealing. Two
      sets of methylidene absorptions observed in Ar and Kr matrices form a persistent
      photoreversible system. The most stable C1 and slightly higher energy planar
      structures of the methylidene complex in the singlet ground state trapped in the
      matrix reproduce the characteristics of the two sets of absorptions. Agostic
      distortion of the methylidene complexes decreases in the order Ti, Zr, Hf and
      increases in the order F, Cl, and Br; the C=Zr and Zr-H stretching frequencies
      increase, and the bonds become shorter. This observation favors the
      characterization of the agostic interaction as a reorganization of charge.

PMID- 17441078
TI  - Microwave-assisted heterogeneous cross-coupling reactions catalyzed by nickel-in
      charcoal (Ni/C).
AB  - A study involving the relatively rare combination of heterogeneous catalysis
      conducted under microwave conditions is presented. Carbon-carbon bond formation,
      including Negishi and Suzuki couplings, can be quickly effected with aryl
      chloride partners by using a base metal (nickel) adsorbed in the pores of
      activated charcoal. Aminations were also studied, along with cross-couplings of
      vinyl alanes with benzylic chlorides as a means to stereodefined allylated
      aromatics. Reaction times for all these processes are typically reduced from
      several hours to minutes in a microwave reactor.

PMID- 17441079
TI  - One-shot double elimination process: a practical and concise protocol for diaryl
      acetylenes.
AB  - A variety of diaryl acetylenes were obtained in good yields when lithium
      hexamethyldisilazide was added to a solution of arylmethyl sulfone, aryl
      aldehyde, and chlorodiethylphosphate in THF. In this one-shot process, a number
      of transformations such as aldol reaction, phosphorylation of aldolate, and
      double elimination of the resulting beta-substituted sulfone proceeded
      successively to afford the desired acetylenes. The one-shot process was
      accelerated by the substitution of halogen atoms on the phenyl groups, and
      unsymmetrically substituted diaryl acetylenes were obtained without contamination
      of the dehalogenated products. Diaryl acetylenes with other substituents such as
      CF3, ethoxycarbonyl, dimethylamino, TMS-acetylene groups, as well as pyridinyl
      and thienyl moieties were also accessible with this method. However, methoxy
      substituted compounds were obtained in moderate yields under the same conditions,
      but the yields were increased when lithium diisopropylamide was used instead.

PMID- 17441080
TI  - Readily synthesized chiral sulfides as reagents for asymmetric epoxidation.
AB  - Chiral oxathianes were designed, synthesized, and successfully used for
      asymmetric sulfur ylide mediated epoxidation. A considerable emphasis has been
      placed upon the design of sulfides with suitable architecture in a small number
      of steps (three or four). The use of (4aR,6S,8aR)-6-isopropenyl-8a
      methyloctahydro-1,4-benzoxathiane in asymmetric epoxidation resulted in good
      diastereo- and enantioselectivity in the formation of stilbene oxide, and (2S,6S)
      2-allyl-2,3,3,6-tetramethyl-1,4-oxathiane produced even better results. Moderate
      to good diastereoselectivities with essentially complete enantioselectivities
      were observed in the formation of alkyl-aryl-, vinyl-aryl-, and propargyl-aryl
      substituted epoxides. The selectivities were rationalized and supported by
      density functional theory calculations.

PMID- 17441081
TI  - Vancomycin analogues containing monosaccharides exhibit improved antibiotic
      activity: a combined one-pot enzymatic glycosylation and chemical diversification
      strategy.
AB  - Many natural products contain carbohydrate moieties that contribute to their
      biological activity. Manipulation of the carbohydrate domain of natural products
      through multiple glycosylations to identify new derivatives with novel biological
      activities has been a difficult and impractical process. We report a practical
      one-pot enzymatic approach with regeneration of cosubstrates to synthesize
      analogues of vancomycin that contain an N-alkyl glucosamine, which exhibited
      marked improvement in antibiotic activity against a vancomycin-resistant strain
      of Enterococcus.

PMID- 17441082
TI  - Ruthenium-catalyzed oxidation of alkenes, alkynes, and alcohols to organic acids
      with aqueous hydrogen peroxide.
AB  - A protocol that adopts aqueous hydrogen peroxide as a terminal oxidant and
      [(Me3tacn)(CF3CO2)2Ru(III)(OH2)]CF3CO2 (1; Me3tacn = 1,4,7-trimethyl-1,4,7
      triazacyclononane) as a catalyst for oxidation of alkenes, alkynes, and alcohols
      to organic acids in over 80% yield is presented. For the oxidation of cyclohexene
      to adipic acid, the loading of 1 can be lowered to 0.1 mol %. On the one-mole
      scale, the oxidation of cyclohexene, cyclooctene, and 1-octanol with 1 mol % of 1
      produced adipic acid (124 g, 85% yield), suberic acid (158 g, 91% yield), and 1
      octanoic acid (129 g, 90% yield), respectively. The oxidative C=C bond-cleavage
      reaction proceeded through the formation of cis- and trans-diol intermediates,
      which were further oxidized to carboxylic acids via C-C bond cleavage.

PMID- 17441083
TI  - Highly enantiomerically enriched planar chiral naphthalene tricarbonylchromium
      complexes.
AB  - Lithiation/electrophile trapping reactions were carried out with the highly
      enantiomerically enriched complex [Cr(5-bromonaphthalene)(CO)3]. Electrophile
      quenching with ClPPh2, PhCHO, and (Me3SiO)2 afforded the enantiomerically
      enriched (>97% ee) planar chiral 5-substituted naphthalene complexes with PPh2,
      CH(Ph)OH, and OH substituents, respectively. Very mild Pd-catalyzed Suzuki
      Miyaura cross-coupling reactions were developed and applied to the highly labile
      [Cr(5-bromonaphthalene)(CO)3] to give nine new planar chiral aryl-, heteroaryl-,
      alkynyl-, and alkenylnaphthalene chromium complexes with high enantiomeric
      purity. The efficient ambient-temperature coupling reactions with borinates
      prepared in situ were also applied to a number of chlorobenzene complexes and to
      aryl and vinyl halides.

PMID- 17441084
TI  - Synthesis of substituted 1,3-diene synthetic equivalents by a Ru-catalyzed diyne
      hydrative cyclization.
AB  - Catalyzed by [CpRu(CH3CN)3]PF6, the hydrative cyclization of dipropargylic
      sulfone substrates provides an effective way to synthesize highly functionalized
      substituted 3-sulfolenes. The amount of water is crucial for the reactivity of
      this cycloisomerization reaction. The scope and limitations of the Ru-catalyzed
      cycloisomerization are discussed. A marked ketone-directing effect was observed
      for the first time in ruthenium-catalyzed cyclizations. A plausible mechanism for
      the ketone-directed cycloisomerization is also rationalized. The utility of this
      method was demonstrated by both sulfur dioxide extrusion of the 3-sulfolenes to
      afford 1,3-dienes and subsequent inter- or intramolecular Diels-Alder reactions.

PMID- 17441085
TI  - Two-dimensional acetylenic scaffolding: extended donor-substituted perethynylated
      dehydroannulenes.
AB  - Starting from (Z)-bis(N,N-diisopropylanilino)-substituted tetraethynylethene
      (TEE), perethynylated octadehydro[12]- and dodecadehydro[18]annulenes were
      prepared by oxidative Hay coupling. The dodecadehydro[18]annulene with six
      peripheral N,N-diisopropylanilino substituents was characterized by X-ray
      crystallography. Elongation of the Z-bisdeprotected TEE by Cadiot-Chodkiewicz
      coupling with 1-bromo-2-(triisopropylsilyl)ethyne provided a Z-configured
      bis(butadiyne), which after alkyne deprotection afforded under Hay coupling
      conditions N,N-diisopropylanilino-substituted perethynylated hexadecadehydro[20]-
      and tetracosadehydro[30]annulenes. The diisopropylanilino substituents enhance
      the properties of these unprecedented all-carbon perimeters in several distinct
      ways. They ensure their solubility, increase their stability, and importantly,
      engage in strong intramolecular charge-transfer interactions with the electron
      accepting all-carbon cores, resulting in intense, bathochromically shifted charge
      transfer bands in the UV/Vis spectra. The charge-transfer character of these
      bands was confirmed by protonation-neutralization experiments. The redox
      properties of the new carbon-rich chromophores were investigated by cyclic
      voltammetry and rotating disk voltammetry, which indicated different redox
      behavior for aromatic (4n+2 pi electrons) and antiaromatic (4n pi electrons)
      dehydroannulenes.

PMID- 17441088
TI  - Molecular oxygen to regenerate Pd(II) active species.
AB  - Palladium(II) catalysis allows various aerobic oxidation reactions, but the
      mechanism of the regeneration of the active catalytic species remains, in many
      cases, undetermined. In recent years, considerable effort has been directed
      toward the comprehension of the reaction of dioxygen with hydridopalladium(II)
      and palladium(0) complexes. This Focus Review highlights the results of these
      experimental and theoretical studies that can contribute to the exploitation of
      the powerful nature of Pd(II) catalysis.

PMID- 17441089
TI  - Photo- and redox-active dendritic molecules with soft, layered nanostructures.
AB  - Molecules with one photoactive group (porphyrin) and multiple redox-active groups
      (ferrocenes) are described. The molecules are based on dendritic frameworks, with
      the ferrocenyl groups attached at the "internal" positions and the porphyrin
      attached at the focal point, leading to a characteristic layer architecture.
      Molecules of up to the third generation were synthesized and examined. The
      results of 1H NMR spectroscopy and fluorescence quenching indicated that the
      ferrocenyl groups at the second layer approach the core porphyrin most closely,
      which is consistent with the results of molecular-dynamics simulations. The
      electrochemistry of the molecules was also examined in detail, and a new formula
      is proposed for the analysis of multiple-electron transfer in these "redox-pool"
      molecules.

PMID- 17441090
TI  - Nanocrystalline Ag from supramolecular stabilization of metals in 4-tert
      butylcalix[4]arene lattices.
AB  - Competition between intermolecular forces is a prime method for directing the
      formation of self-assembled structures without resorting to the use of covalently
      modified host molecules. In this study, we demonstrate how the competition
      between hydrogen bonding, coordinate bonding, and van der Waals interactions
      guides the formation of a complex crystalline clathrate based on a Ag
      ethylenediamine coordination complex and 4-tert-butylcalix[4]arene. Owing to the
      coordinative flexibility of Ag and the stabilizing interactions with the
      calixarene framework, a four-coordinate Ag complex is included in the structure.
      Subsequent removal of the amine by heating the crystalline inclusion compound
      results in reduction of the Ag+ ion such that metallic Ag nanocrystals are
      formed, thus indicating that this self-assembly approach is a viable method for
      obtaining simple calixarene frameworks loaded with silver. In the light of the
      experimental evidence, we comment on how this process relates to the reduction of
      silver in other systems.

PMID- 17441091
TI  - Tuning the formation of cadmium(II) urocanate frameworks by control of reaction
      conditions: crystal structure, properties, and theoretical investigation.
AB  - The reaction of cadmium(II) perchlorate with urocanic acid under different
      conditions created three novel coordination compounds: [Cd2(L2)2-(L3)2(H2O)8]
      (1), {[Cd(L)(L2)](H2O)(1/2)}n (2), and {[Cd(L3)2](H2O)(3/2)(EtOH)}n (3), in which
      L, L2, and L3 are three urocanate tautomers. Complex 1 consists of two separate
      mononuclear units with different urocanate tautomers, which self-assemble into a
      3D hydrogen-bonding network constructed by alternating 2D layers, whereas
      complexes 2 and 3 self-assemble into 3D alpha-polonium and four-fold
      interpenetrated diamondoid networks, respectively. The tautomerism of the
      urocanate ligands and the enormous structural diversity of their complexes are
      present in this system, which illustrates that the reaction temperature,
      pressure, and the metal ions themselves act cooperatively to tune the tautomerism
      of the ligands and the frameworks of their metal coordination compounds. The
      fluorescence-emission and nitrogen-adsorption properties of these complexes are
      also investigated.

PMID- 17441092
TI  - Dendrimeric bisphosphonates for multivalent protein surface binding.
AB  - A single weak-binding event is multiplied into an efficient receptor site for
      protein surfaces (<10(-1) to >10(6) M(-1) in buffered aqueous solution) in a
      biomimetic fashion. This has hitherto been done with natural host/guest pairs,
      but not with artificial receptors. The organic reaction presented is one of very
      few that enable chemists to fuse multiple ionic building blocks covalently in
      highly polar solution; this one-pot reaction proceeds with virtually quantitative
      yield. According to this concept, other building blocks with aldehyde groups can
      likewise be multiplied into monodisperse functional dendrimers. Small basic
      proteins are bound by octameric dendrimers in 1:1 or 1:2 complexes with
      millimolar to submicromolar affinities. The complexation event is studied
      independently in buffered aqueous solution by three different spectroscopic
      methods (PFG-LED, UV/Vis, and fluorescence). Potential new applications include
      recombinant protein purification through Arg tags on immobilized dendrimers and
      on/off switching of protein function by reversible active-site capping of
      enzymes.

PMID- 17441093
TI  - Design of dual-emission chemosensors for ratiometric detection of ATP
      derivatives.
AB  - Nucleoside pyrophosphate (nucleoside PP) derivatives are widespread in living
      cells and play pivotal roles in various biological events. We report novel
      fluorescence chemosensors for nucleoside PPs that make use of coordination
      chemistry. The chemosensors, which contain two Zn(II)-dipicolylamine units, bind
      strongly to nucleoside PPs (K(app)>10(6) M(-1)) in aqueous solution and sense
      them by a dual-emission change. Detailed fluorescence and UV/Vis spectral studies
      revealed that the emission changes of the chemosensors upon binding to nucleoside
      PPs can be ascribed to the loss of coordination between Zn(II) and the acridine
      fluorophore. This is a unique sensing system based on the anion-induced
      rearrangement of the coordination. Furthermore, we demonstrated the utility of
      these chemosensors in real-time monitoring of two important biological processes
      involving nucleoside PP conversion: the apyrase-catalyzed hydrolysis of
      nucleoside PPs and the glycosyl transfer catalyzed by beta-1,4
      galactosyltransferase.

PMID- 17441094
TI  - Structure-dependent photoinduced electron transfer in fullerodendrimers with
      light-harvesting oligophenylenevinylene terminals.
AB  - Oligophenylenevinylene (OPV)-terminated phenylenevinylene dendrons G1-G4 with
      one, two, four, and eight "side-arms", respectively, were prepared and attached
      to C60 by a 1,3-dipolar cycloaddition of azomethine ylides generated in situ from
      dendritic aldehydes and N-methylglycine. The relative electronic absorption of
      the OPV moiety increases progressively along the fullerodendrimer family C60G1
      C60G4, reaching a 99:1 ratio for C60G4 (antenna effect). UV/Vis and near-IR
      luminescence and transient absorption spectroscopy was used to elucidate
      photoinduced energy and electron transfer in C60G1-C60G4 as a function of OPV
      moiety size and solvent polarity (toluene, dichloromethane, benzonitrile), taking
      into account the fact that the free-energy change for electron transfer is the
      same along the series owing to the invariability of the donor-acceptor couple.
      Regardless of solvent, all the fullerodendrimers exhibit ultrafast OPV-->C60
      singlet energy transfer. In CH2Cl2, the OPV-->C60 electron transfer from the
      lowest fullerene singlet level ((1)C60*) is slightly exergonic (deltaG(CS)
      approximately = 0.07 eV), but is observed, to an increasing extent, only in the
      largest systems C60G2-C60G4 with lower activation barriers for electron transfer.
      This effect has been related to a decrease of the reorganization energy upon
      enlargement of the molecular architecture. Structural factors are also at the
      origin of an unprecedented OPV-->C60 electron transfer observed for C60G3 and
      C60G4 in apolar toluene, whereas in benzonitrile, electron transfer occurs in all
      cases. Monitoring of the lowest fullerene triplet state by sensitized singlet
      oxygen luminescence and transient absorption spectroscopy shows that this level
      is populated through intersystem crossing and is not involved in photoinduced
      electron transfer.

PMID- 17441095
TI  - Assembly of DNA nanostructures with branched tris-DNA.
AB  - Branched tris-DNA, in which two oligonucleotides of the same sequence and one
      other oligonucleotide of a different sequence are connected with a rigid central
      linker, was prepared chemically by using a DNA synthesizer. Two branched tris-DNA
      molecules with complementary DNA sequences form dimer and tetramer as well as
      linear and spherical oligomer complexes. The complex formation was studied by
      UV/thermal denaturation, enzyme digestion, gel electrophoresis, and AFM imaging.

PMID- 17441096
TI  - NMR spectroscopic observation of a metal-free acetylide anion.
AB  - A metal-free acetylide was observed by using NMR spectroscopy. Metal-free
      acetylides are closely related to reactive intermediates (carbanions) in
      solution; therefore, they have been regarded as unobservable species. However, we
      generated this highly reactive and unstable species through the deprotonation of
      phenylacetylene by using the strong nonmetallic phosphazene base tBu-P4. In the
      presence of tBu-P4, the J coupling between the ethynyl carbon and hydrogen nuclei
      (1J(C,H)) of phenylacetylene disappeared; this indicates the deprotonation of the
      alkyne terminal. Furthermore, a large low-field shift (approximately 90 ppm) of
      the alkyne carbon resonance was observed. We concluded that we have observed a
      metal-free carbanion with a formal charge on an sp-hybridized carbon atom for the
      first time.

PMID- 17441097
TI  - Stereospecific and stereodivergent construction of tertiary and quaternary carbon
      centers through switchable directed/nondirected allylic substitution.
AB  - This study introduces the ortho-diphenylphosphanylbenzoate (o-DPPB)/o-DPPB oxide
      system as a switchable directing/nondirecting leaving group in a copper-mediated
      allylic substitution with Grignard and organozinc reagents. With this system, the
      regioselective, stereospecific, and stereodivergent construction of quaternary as
      well as tertiary carbon centers is possible in a reliable and predictable
      fashion. Starting from one substrate enantiomer, both optical antipodes of the
      substitution products are readily available. Hence, this methodology features
      reversed polarity in comparison to established enolate alkylation chemistry and
      may be an interesting alternative, particularly for the construction of
      quaternary stereogenic carbon centers.

PMID- 17441098
TI  - An environmentally benign process for the hydrogenation of ketones with
      homogeneous iron catalysts.
AB  - Iron complexes generated in situ catalyze homogeneously the transfer
      hydrogenation of aliphatic and aromatic ketones by utilizing 2-propanol as a
      hydrogen donor in the presence of base. The influence of different reaction
      parameters on the catalytic activity is investigated in detail by applying a
      three-component catalyst system composed of an iron salt, 2,2':6',2''
      terpyridine, and PPh3. The scope and limitations of the described catalyst is
      shown in the reduction of 11 different ketones. In most cases, high conversion
      and excellent chemoselectivity are obtained. Mechanistic studies indicate a
      monohydride reaction pathway for the homogeneous iron catalyst.

PMID- 17441099
TI  - Microwave-assisted synthesis of a superparamagnetic surface-functionalized porous
      Fe3O4/C nanocomposite.
AB  - An Fe3O4/C nanocomposite was synthesized in a microwave-assisted hydrothermal
      reaction. This green wet-chemical approach is simple, low-cost, and ideal for
      large-scale production. The resulting composite material was characterized by
      transmission electron microscopy, powder X-ray diffraction, energy-dispersive X
      ray spectroscopy, Brunauer-Emmett-Teller analysis, X-ray photoelectron
      spectroscopy, vibrating sample magnetometry, and UV/Vis spectroscopy. The product
      possesses porous structures and exhibits superparamagnetic behavior.
      Interestingly, its functional groups were inherited from the starting materials.
      This hydrophilic and biocompatible nanocomposite may find applications in
      catalysis, separation, adsorption, and bionanotechnology.

PMID- 17441100
TI  - Ring-closing olefin metathesis for the synthesis of benzene derivatives.
AB  - Benzene derivatives were synthesized in excellent yield from 1,4,7-trien-3-ols by
      tandem ruthenium-catalyzed ring-closing olefin metathesis (RCM)/dehydration. The
      method was extended to the tandem RCM/oxidation process to obtain phenol and
      aniline derivatives. This method displays many advantages over aromatic
      substitution-based classical routes.

PMID- 17441101
TI  - Removal of toxic metal-ion pollutants from water by using chemically modified
      carbon powders.
AB  - The thermodynamics of and the kinetic parameters controlling the sequestration of
      the toxic heavy-metal ion Cd(II) from aqueous media by using a novel material
      consisting of glassy carbon microspheres (10-20 microm in diameter) chemically
      modified with L-cysteine methyl ester are presented. In an effort to reduce the
      cost and increase the efficiency of toxic-metal-ion removal, this modification
      strategy was expanded to attach L-cysteine methyl chemically ester to less
      expensive graphite powders (2-20 microm in diameter), and the thermodynamic and
      kinetic parameters of the sequestration of Cd(II), Cu(II), and As(III) toxic
      metal ions are presented. It was found that the use of chemically modified
      graphite powder greatly increased both the rate and the amount of metal ions
      removed from aqueous media. This work has important potential applications to
      filtration of drinking water and environmental remediation.

PMID- 17441102
TI  - Comparative theoretical study of N-heterocyclic carbenes and other ligands bound
      to Au(I).
AB  - The bonding strength of N-heterocyclic carbene (NHC) ligands to a neutral AuCl
      test moiety are compared to that of several phosphanes and other ligands. Of the
      ligands studied, the NHCs clearly form the strongest bonds to AuCl. A simplified
      triangular CN2 model is also introduced for the NHCs.

PMID- 17441104
TI  - Carbon-nanotube-based hybrid materials: nanopeapods.
AB  - This review article focuses on the structures and properties of novel hybrid
      nanocarbon materials, which are created by incorporating atoms and molecules into
      the hollow spaces of carbon nanotubes (CNTs); thus they are called nanopeapods.
      After dealing with synthesis procedures, we discuss the structures and electronic
      properties of the hybrid materials based on high-resolution transmission electron
      microscopy (HRTEM), electron energy-loss spectroscopy (EELS), X-ray and electron
      diffraction, scanning tunneling microscopy (STM), and field-effect transistor
      transport measurements. Utilization of the low-dimensional nanosized spaces of
      CNTs to produce novel low-dimensional nanocluster, nanowire, and nanotube
      materials is also discussed.

PMID- 17441105
TI  - The reactive intermediate of catalytic borohydride reduction by Schiff base
      cobalt complexes.
AB  - The key reactive intermediate of borohydride reduction catalyzed by Schiff base
      cobalt complexes is proposed to be the dichloromethylcobalt hydride with a sodium
      cation, based on experimental and theoretical studies. It was revealed that
      chloroform is not the solvent but the reactant that activates the cobalt
      catalyst. The substrate carbonyl compounds are fixed and activated by the alkali
      cation, which is captured by the oxygen atoms of the planar ligand and the
      chlorine atom of the axial ligand, and attacked by the hydride on the cobalt atom
      via a six-membered-like transition state to afford the corresponding alcohol.

PMID- 17441106
TI  - Synthesis of anatase TiO2 nanoparticles with beta-cyclodextrin as a
      supramolecular shell.
AB  - We report a novel, green hydrothermal-synthesis route to well-dispersed anatase
      TiO2 nanoparticles with particle sizes of 9-16 nm in the presence of beta-CD
      (beta-cyclodextrin). During the synthesis process, the CD-containing synthesis
      mixture assembled in both longitudinal and latitudinal directions. Driven by the
      interaction between molecules, the beta-CDs assembled in the longitudinal
      direction to form long-chain compounds, whereas in the latitudinal direction,
      they tended to form regular aggregates through coordination with the Ti species
      from the hydrolysis of tetrabutyl titanate. In view of the effect of the
      coordination and the steric hindrance of beta-CDs as a supramolecular shell,
      homogeneous nuclei and slow growth of TiO2 crystals during the synthesis process
      was observed, which was responsible for the formation of uniform TiO2
      nanoparticles. The low beta-CD dosage and the high product yield (>90%)
      demonstrated well the potential of this synthesis route in the large-scale
      industrial production of anatase nanoparticles.

PMID- 17441107
TI  - Polymer-assisted solution-phase synthesis and neurite-outgrowth-promoting
      activity of 15-deoxy-delta(12,14)-PGJ2 derivatives.
AB  - An efficient solution-phase synthesis of rac-15-deoxy-delta(12,14)-PGJ2 (15dPGJ2)
      derivatives that contain variable alpha and omega chains based on a polymer
      assisted strategy and their neurite-outgrowth-promoting activity are described.
      The strategy for the synthesis of PGJ2 derivatives involves the use of a vinyl
      iodide bearing cyclopentenone as a key intermediate, which undergoes Suzuki
      Miyaura coupling and subsequent Lewis acid catalyzed aldol condensation for
      incorporation of the omega and alpha chains, respectively. For easy access to the
      PGJ2 derivatives, a polymer-supported catalyst and scavengers were adapted for
      use in these four diverse steps, in which workup and purification can be
      performed by simple filtration of the solid-supported reagents. By using this
      methodology, we succeeded in the synthesis of 16 PGJ2 derivatives with four alkyl
      boranes and four aldehydes. The neurite-outgrowth-promoting activity of the 16
      synthetic compounds in PC12 cells revealed that the side-chains play a major role
      in modulating their biological activity. The carboxylic acid on the alpha chain
      improved the biological activity, although it was not absolutely required.
      Furthermore, a PGJ2 derivative with a phenyl moiety on the omega chain was found
      to exhibit an activity comparable to that of natural 15dPGJ2.

PMID- 17441108
TI  - Anions and polyanions of oligoindenopyrenes: modes of electron delocalization and
      dimerization.
AB  - A series of pyrene-based polycyclic aromatic compounds, indeno[cd]pyrene,
      diindeno[cd,fg]pyrene, diindeno[cd,jk]pyrene, tris-(tert
      butylindeno[cd,fg,jk])pyrene, and tetrakis-(tert-butylindeno[cd,fg,jk,mn])pyrene,
      were reduced with alkali metals in [D8]tetrahydrofuran, and the resulting anions
      were studied by NMR spectroscopy. It was found that the diatropic character of
      the dianions obtained depends on the number of annulated indeno groups. When one
      such group is present, a paratropic dianion is obtained, which is similar to the
      dianion of the parent pyrene; the effect, however, is weak. When more indeno
      groups are annulated, the dianions become diatropic owing to the greater number
      of five-membered rings that can acquire aromatic character as a result of
      reduction. The 1H NMR chemical shifts of tetrakis-(tert
      butylindeno[cd,fg,jk,mn])pyrene in the neutral state show an interesting
      dependence on concentration that reflects an association of the molecules in
      solution by pi stacking. This phenomenon was not observed for the reduced
      species. The trianion radicals of tris-(tert-butylindeno[cd,fg,jk])pyrene and
      tetrakis-(tert-butylindeno[cd,fg,jk,mn])pyrene undergo reductive dimerization and
      form bilayered hexaanions.

PMID- 17441109
TI  - Metallomacrocycles that incorporate cofacially aligned diimide units.
AB  - Pyromellitic diimide and naphthalene diimide moieties were incorporated into
      hemilabile phosphanylalkyl thioether ligands. These ligands reacted with
      [Cu(CH3CN)4]PF6 and [Rh(NBD)Cl]2 (NBD = norbornadiene) by the weak-link approach
      to form condensed intermediates. Upon reaction of each diimide ligand with these
      transition-metal precursors, the two diimide units became cofacially aligned
      within a supramolecular macrocyclic architecture. The introduction of ancillary
      ligands to each of these condensed intermediates caused the weak thioether-metal
      bonds to break, thus generating a large macrocycle in which the distance between
      diimide units is significantly larger than for the condensed intermediates. The
      two Rh(I) cationic condensed intermediates were characterized by single-crystal X
      ray diffraction studies, and the electrochemical activity of these macrocycles
      was demonstrated with the naphthalene diimide-Cu(I) macrocycles.

PMID- 17441110
TI  - Coordination behavior of sterically protected phosphaalkenes on the AuCl moiety
      leading to catalytic 1,6-enyne cycloisomerization.
AB  - Mes*-substituted 2,3-dimethyl-1,4-diphosphabuta-1,3-diene, 1,2-diphenyl-3,4
      diphosphinidenecyclobutene, 2,2-bis(methylsulfanyl)-1-phosphaethene, and 3,3
      diphenyl-1,3-diphosphapropenes (Mes* = 2,4,6-tri-tert-butylphenyl) were employed
      as P ligands of gold(I) complexes. The (E,E)-2,3-dimethyl-1,4-diphosphabuta-1,3
      diene functioned as a P2 ligand for digold(I) complex formation with or without
      intramolecular Au-Au contact, which depends on the conformation of the 1,3
      diphosphabuta-1,3-diene. The 1,2-diphenyl-3,4-diphosphinidenecyclobutene, which
      has a rigid s-cis P=C-C=P skeleton, afforded the corresponding digold(I)
      complexes with a slight distortion of the planar diphosphinidenecyclobutene
      framework and intramolecular Au-Au contact. In the case of the 2,2
      bis(methylsulfanyl)-1-phosphaethene, only the phosphorus atom coordinated to
      gold, and the sulfur atom showed almost no intra- or intermolecular coordination
      to gold. On the other hand, the 1,3-diphosphapropenes behaved as nonequivalent P2
      ligands to afford the corresponding mono- and digold(I) complexes. Some
      phosphaalkene-gold(I) complexes showed catalytic activity for 1,6-enyne
      cycloisomerization without cocatalysts such as silver hexafluoroantimonate.

PMID- 17441111
TI  - Crystalline vanadium pentoxide with hierarchical mesopores and its capacitive
      behavior.
AB  - Crystalline vanadium pentoxide with hierarchical mesopores was synthesized by
      using a CTAB/BMIC cotemplate (CTAB = cetyltrimethylammonium bromide, BMIC = 1
      butyl-3-methylimidazolium chloride). The material was fully characterized by SEM,
      TEM, N2 adsorption-desorption, XRD, XPS, and CV methods. By elaborate adjustment
      of the template proportions, the distribution and size of the hierarchical pores
      were tuned successfully. CTAB cationic surfactant contributed more to the larger
      mesopores, whereas BMIC ionic liquid was beneficial in forming the smaller
      nanopores. The vanadium-containing anions combined with CTA+ micelles and BMI+
      rings through electrostatic interactions. The CTA(+)-O(VO)O(-)-BMI(+) entities
      built up an orderly array, which finally formed the hierarchical mesoporous
      framework during thermal treatment. The mesoporous vanadium pentoxide directed by
      the cotemplate of CTAB/BMIC = 1:1 showed many orderly crystalline structures and
      demonstrated a large capacitance (225 F g(-1)); it is thus a promising material
      for electrochemical capacitors. Two alternative solutions to the disappearance of
      capacitance due to insertion of K+ are proposed in view of possible future
      applications.

PMID- 17441112
TI  - Kinetic studies prove high catalytic activity of a diene-rhodium complex in 1,4
      addition of phenylboronic acid to alpha,beta-unsaturated ketones.
AB  - In the 1,4-addition of phenylboronic acid to alpha,beta-unsaturated ketones,
      [Rh(OH)(cod)]2 has a much higher catalytic activity than [Rh(OH)(binap)]2 (cod =
      1,5-cyclooctadiene, binap = 2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl).
      Kinetic studies revealed that the rate-determining transmetalation step in the
      catalytic cycle has a large rate constant when [Rh(OH)(cod)]2 is used.

PMID- 17441113
TI  - One-pot synthesis of lactams from cycloalkanes and tert-butyl nitrite by using N
      hydroxyphthalimide as key catalyst.
AB  - Lactams were successfully synthesized in the one-pot reaction of cycloalkanes and
      tBuONO in the presence of N-hydroxyphthalimide as a key catalyst. Cyclododecane
      and cyclohexane were treated with tBuONO followed by triethylamine and then
      cyanuric chloride in a one-pot manner to give laurolactam and epsilon
      caprolactam, respectively, in good yields. The Beckmann rearrangement of oximes
      by cyanuric chloride was found to be accelerated by the use of 1,1,1,3,3,3
      hexafluoro-2-propanol as solvent. The method provides the first successful
      environmentally benign direct synthetic route to lactams from cycloalkanes
      without the formation of any salt.

PMID- 17441114
TI  - Synthesis of urea-tethered disaccharides in water.
AB  - A new method for the synthesis of urea-linked disaccharides in aqueous media has
      been developed. The key feature of our approach is two strained Steyermark-type
      gluco- and galactopyranosyl oxazolidinones. Each oxazolidinone is attached to a
      pyranose ring in a di-equatorial trans-annulation framework. Reaction of these
      oxazolidinones with 4-aminohexopyranose in water proceeded smoothly to afford the
      urea-tethered cellobiose and lactose analogues. The galactose-type oxazolidinone
      proved to be more reactive than the glucose-type, which is explained by the
      presence of an axial hydroxy group at C4 in the former.

PMID- 17441115
TI  - Asymmetric Baylis-Hillman reactions promoted by chiral imidazolines.
AB  - The coupling of electrophiles with activated alkenes by using tertiary amines or
      phosphines is generally known as the Baylis-Hillman reaction. It is a useful and
      atom-economical carbon-carbon bond-forming reaction that generates
      multifunctionalized products. This reaction is notoriously slow; yields are often
      low and substrate-dependent. The asymmetric reaction is still limited especially
      for unactivated olefins such as acrylates. Imidazolines have been developed as
      ligands in metal-catalyzed reactions and have also been used as privileged
      structures in diversity-oriented synthesis. A series of novel chiral imidazolines
      were prepared and used to develop asymmetric Baylis-Hillman reactions. These
      imidazolines promote the reactions of various aromatic aldehydes with unactivated
      acrylates. Enantiomeric excesses of up to 60% and high yields were obtained by
      using stoichiometric amounts of the promoter. Furthermore, the imidazolines are
      also suitable promoters for the reactions between aromatic aldehydes and alkyl
      vinyl ketones. Enantiomeric excesses of up to 78% and high yields were obtained
      with 50 mol % of an imidazoline with a chiral methylnaphthyl group. These chiral
      imidazolines are easily prepared from commercially available amino alcohols and
      can be easily recovered for reuse without loss of product enantioselectivity.

PMID- 17441116
TI  - Metallodielectric hollow shells: optical and catalytic properties.
AB  - Metallodielectric composites with tunable optical properties were prepared by
      layer-by-layer assembly of gold nanorods on polystyrene (PS) spheres and
      subsequent deposition of SiO2 or TiO2 encapsulating shells through a sol-gel
      process. The optical properties of the core-shells were tailored in the visible
      and the near-infrared region through the gold nanorod aspect ratio and the gold
      nanoparticle density. Removal of the PS core by dissolution in an appropriate
      solvent, such as THF, yielded metallodielectric hollow shells with optical
      properties identical to those of the original composites. The presence of gold
      and the porosity of the SiO2 or TiO2 shells, suitable to allow diffusion of
      reactants and products, make these materials of interest as catalysts, as
      demonstrated by the reduction of potassium hexacyanoferrate(III) with NaBH4.

PMID- 17441117
TI  - Nd-doped TiO2 nanorods: preparation and application in dye-sensitized solar
      cells.
AB  - Monodispersed Nd-doped TiO2 nanorods (20 nm x 2 nm) were synthesized by
      solvothermal methods and characterized by TEM, XRD, and EDS. Application of the
      nanorods for modifying conventional photoanodes in dye-sensitized solar cells
      (DSSCs) was investigated. Data show that, after modification, an enhancement of
      the incident-photon-to-current conversion efficiency (IPCE) in the whole range of
      visible light was observed and an increase of 33.3% for overall conversion
      efficiency was achieved. Our mechanistic proposal is that Nd ions doped on TiO2
      nanorods to some extent enhance the injection of excited electrons and decrease
      the recombination rate of the injected electrons.

PMID- 17441118
TI  - Amine-templated one-dimensional metal sulfates including a mixed-valent Fe
      compound with a half-kagome structure.
AB  - Organically templated metal sulfates are relatively new. Six amine-templated
      transition-metal sulfates with different types of chain structures, including a
      novel iron sulfate with a chain structure corresponding to one half of the kagome
      structure, were synthesized by hydro/solvothermal methods. Amongst the one
      dimensional metal sulfates, [C10N2H10][Zn(SO4)Cl2] (1) is the simplest, being
      formed by corner-linked ZnO2Cl2 and SO4 tetrahedra. [C6N2H18][Mn(SO4)2(H2O)2] (2)
      and [C2N2H10][Ni(SO4)2(H2O)2] (3) have ladder structures comprising four-membered
      rings formed by SO4 tetrahedra and metal-oxygen octahedra, just as in the mineral
      krohnkite. [C4N2H12][V(III)(OH)(SO4)2]H2O (4) and [C4N2H12][VF3(SO4)] (5) exhibit
      chain topologies of the minerals tancoite and butlerite, respectively. The
      structure of [C4N2H12][H3O][Fe(III)Fe(II) F6(SO4)] (6) is noteworthy in that it
      corresponds to half of the hexagonal kagome structure. It exhibits ferrimagnetic
      properties at low temperatures and the absence of frustration, unlike the mixed
      valent iron sulfate with the full kagome structure.

PMID- 17441120
TI  - Shape-persistent aromatic amide oligomers: new tools for supramolecular
      chemistry.
AB  - With an increasing number of folding and helical structures available, chemists
      have begun to pay greater attention to the functions of this family of
      structurally unique oligomers. Hydrogen-bonding-mediated aromatic oligoamide
      foldamers have the features of good structural predictability, synthetic
      facility, and structural modification, which make them very promising as
      scaffolds or platforms for supramolecular chemistry. Recent advances in the
      applications of this class of shape-persistent oligomers in the promoted
      synthesis of macrocycles, design of new nonring receptors, supramolecular self
      assembly, molecular encapsulation, and reaction acceleration, are highlighted in
      this Focus Review.

PMID- 17441121
TI  - Asymmetric resolution in ester reduction by NaBH4 at the interface of aqueous
      aggregates of amino acid, peptide, and chiral-counterion-based cationic
      surfactants.
AB  - This study provides insight into the physicochemical aspects of aqueous
      aggregates that comprise amino acid, peptide, and chiral-counterion-based
      cationic surfactants and their correlation with the proficiency of asymmetric
      resolution in ester reduction. The effects of the structural differences in the
      naturally occurring amino acid based and synthetic chiral-counterion-containing
      gemini surfactants on the surface properties as well as on other microstructural
      parameters were studied and correlated to the varied head groups of the
      surfactants. The supramolecular chirality induced from the head-group region of
      chiral amphiphiles in aqueous self-aggregates is evident from circular dichroism,
      scanning electron microscopy, and transmission electron microscopy studies. This
      large-scale chirality at the interface of self-aggregates was exploited towards
      asymmetric resolution in ester reduction by NaBH4. An enantiomeric excess of 53%
      ((R)-2-phenylpropan-1-ol) was found in the case of the n-hexyl ester of 2
      phenylpropionic acid as substrate in the aqueous aggregate of N,N'-dihexadecyl
      N,N,N',N'-tetramethyl-N,N'-ethanediyldiammonium diquinate. Thus, a simple and
      environmentally benign pathway for asymmetric resolution in ester reduction by
      sodium borohydride alone is reported, which utilizes the varied spatial asymmetry
      at the interface of aqueous aggregates of cationic chiral amphiphiles.

PMID- 17441122
TI  - Photo-cross-linked small-molecule microarrays as chemical genomic tools for
      dissecting protein-ligand interactions.
AB  - We have developed a unique photo-cross-linking approach for immobilizing a
      variety of small molecules in a functional-group-independent manner. Our approach
      depends on the reactivity of the carbene species generated from
      trifluoromethylaryldiazirine upon UV irradiation. It was demonstrated in model
      experiments that the photogenerated carbenes were able to react with every small
      molecule tested, and they produced multiple conjugates in most cases. It was also
      found in on-array immobilization experiments that various small molecules were
      immobilized, and the immobilized small molecules retained their ability to
      interact with their binding proteins. With this approach, photo-cross-linked
      microarrays of about 2000 natural products and drugs were constructed. This photo
      cross-linked microarray format was found to be useful not merely for ligand
      screening but also to study the structure-activity relationship, that is, the
      relationship between the structural motif (or pharmacophore) found in small
      molecules and its binding affinity toward a protein, by taking advantage of the
      nonselective nature of the photo-cross-linking process.

PMID- 17441123
TI  - A method of orthogonal oligosaccharide synthesis leading to a combinatorial
      library based on stationary solid-phase reaction.
AB  - A new, efficient synthesis of oligosaccharides, which involves solid-phase
      reactions without mixing in combination with an orthogonal-glycosylation
      strategy, is described. Despite a great deal of biological interest, the
      combinatorial chemistry of oligosaccharides is an extremely difficult subject.
      The problems include 1) lengthy synthetic protocols required for the synthesis
      and 2) the variety of glycosylation conditions necessary for individual
      reactions. These issues were addressed and solved by using the orthogonal
      coupling protocol and the application of a temperature gradient to provide
      appropriate conditions for individual reactions. Furthermore, we succeeded in
      carrying out solid-phase reactions with neither mechanical mixing nor flow. In
      this report, the synthesis of a series of trisaccharides, namely, alpha/beta-L
      Fuc-(1-->6)-alpha/beta-D-Gal-(1-->2/3/4/6)-alpha/beta-D-Glc-octyl, is reported to
      demonstrate the eligibility of the synthetic method in combinatorial chemistry.

PMID- 17441124
TI  - Thermotropic liquid crystals based on extended 2,5-disubstituted-1,3,4
      oxadiazoles: structure-property relationships, variable-temperature powder X-ray
      diffraction, and small-angle X-ray scattering studies.
AB  - A class of extended 2,5-disubstituted-1,3,4-oxadiazoles R1-C6H4-{OC2N2}-C6H4-R2
      (R1 = R2 = C10H21O 1 a, p-C10H21O-C6H4-C[triple bond]C 3 a, p-CH3O-C6H4-C[triple
      bond]C 3 b; R1 = C10H21O, R2 = CH3O 1 b, (CH3)2N 1 c; F 1 d; R1 = C10H21O-C6H4
      C[triple bond]C, R2 = C10H21O 2 a, CH3O 2 b, (CH3)2N 2 c, F 2 d) were prepared,
      and their liquid-crystalline properties were examined. In CH2Cl2 solution, these
      compounds displayed a room-temperature emission with lambda(max) at 340-471 nm
      and quantum yields of 0.73-0.97. Compounds 1 d, 2 a-2 d, and 3 a exhibited
      various thermotropic mesophases (monotropic, enantiotropic nematic/smectic),
      which were examined by polarized-light optical microscopy and differential
      scanning calorimetry. Structure determination by a direct-space approach using
      simulated annealing or parallel tempering of the powder X-ray diffraction data
      revealed distinctive crystal-packing arrangements for mesogenic molecules 2 b and
      3 a, leading to different nematic mesophase behavior, with 2 b being monotropic
      and 3 a enantiotropic in the narrow temperature range of 200-210 degrees C. The
      structural transitions associated with these crystalline solids and their
      mesophases were studied by variable-temperature X-ray diffractometry.
      Nondestructive phase transitions (crystal-to-crystal, crystal-to-mesophase,
      mesophase-to-liquid) were observed in the diffractograms of 1 b, 1 d, 2 b, 2 d,
      and 3 a measured at 25-200 degrees C. Powder X-ray diffraction and small-angle X
      ray scattering data revealed that the structure of the annealed solid residue 2 b
      reverted to its original crystal/molecular packing when the isotropic liquid was
      cooled to room temperature. Structure-property relationships within these
      mesomorphic solids are discussed in the context of their molecular structures and
      intermolecular interactions.

PMID- 17441125
TI  - Effect of lithia and substrate on the electrochemical performance of a
      lithia/cobalt oxide composite thin-film anode.
AB  - Highly porous reticular Li2O/CoO composite thin films fabricated by electrostatic
      spray deposition were investigated by using X-ray diffraction, scanning electron
      microscopy, galvanostatic cell-cycling measurements, and AC impedance
      spectroscopy measurements. The results of the electrochemical tests indicate that
      the initial coulombic efficiency and capacity retention are dependent on Li2O
      content and the specific surface area of the deposited layer. Irrespective of the
      type of substrate, the electrode gave the best electrochemical performance when
      the molar ratio of Li to Co was controlled at 1:1. At the optimal composition, at
      0.2 C the initial coulombic efficiency was as high as 81.9% and 83.6% for the
      film on Cu foil and on porous Ni, respectively. The Li2O/CoO (Li/Co = 1:1) films
      on Ni foam and Cu foil had sustained capacities of up to 790 and 715 mAh g(-1),
      respectively, at a rate of 1 C over 100 cycles at 25 degrees C. Similar cycling
      experiments carried out at 70 degrees C showed that the capacity is temperature
      sensitive, and it exhibited reversible capacities as high as 1018 (Cu foil) and
      1269 mAh g(-1) (Ni foam) for up to 100 cycles. The thin-film electrodes on Ni
      foam always performed better than those on Cu foil. Cycling at elevated
      temperature (70 degrees C) also resulted in a significant increase in capacity.

PMID- 17441126
TI  - Halide-anion binding by singly and doubly N-confused porphyrins.
AB  - The halide-binding properties of N-confused porphyrin (NCP, 1) and doubly N
      confused porphyrins (trans-N2CP (2), cis-N2CP (3)) were examined in CH2Cl2. In
      the free-base forms, cis-N2CP (3) showed the highest affinity to each anion (Cl-,
      Br-, I-) with association constants Ka = 7.8x10(3), 1.9x10(3), and 5.8x10(2) M(
      1), respectively. As metal complexes, on the other hand, trans-N2CP 2-Cu
      exhibited the highest affinity to Cl-, Br-, and I- with Ka = 9.0x10(4),
      2.7x10(4), and 1.9x10(3) M(-1), respectively. The corresponding Ka values for cis
      N2CP 3-Cu and NCP 1-Cu were about 1/10 and 1/2, respectively, of those of 2-Cu.
      With the help of density functional theory (DFT) calculations and complementary
      affinity measurements of a series of trisubstituted N-confused porphyrins, the
      efficient anion binding of NCPs was attributed to strong hydrogen bonding at the
      highly polarized NH moieties owing to the electron-deficient C6F5 groups at meso
      positions as well as the ideally oriented dipole moments and large molecular
      polarizability. The orientation and magnitude of the dipole moments in NCPs were
      suggested to be important factors in the differentiation of the affinity for
      anions.

PMID- 17441127
TI  - Enantio- and diastereoselective total synthesis of (+)-panepophenanthrin, a
      ubiquitin-activating enzyme inhibitor, and biological properties of its new
      derivatives.
AB  - The asymmetric total synthesis of (+)-panepophenanthrin, an inhibitor of
      ubiquitin-activating enzyme (E1), has been accomplished using catalytic
      asymmetric alpha aminoxylation of 1,4-cyclohexanedione monoethylene ketal as a
      key step, followed by several diastereoselective reactions. The biomimetic Diels
      Alder reaction of a monomer precursor was found to proceed efficiently in water.
      The investigation of the biological properties of new derivatives of (+)
      panepophenanthrin enabled us to develop new cell-permeable E1 inhibitors, RKTS
      80, -81, and -82.

PMID- 17441128
TI  - Origin of the pi-facial stereoselectivity in the addition of nucleophilic
      reagents to chiral aliphatic ketones as evidenced by high-level ab initio
      molecular-orbital calculations.
AB  - Ab initio molecular-orbital (MO) calculations were carried out, at the MP2/6
      311++G(d,p)//MP2/6-31G(d) level, to investigate the conformational Gibbs energy
      of alkyl 1-cyclohexylethyl ketones, cyclo-C6H11CHCH3-CO-R (R = Me, Et, iPr, and
      tBu). In each case, one of the equatorial conformations was shown to be the most
      stable. Conformers with the axial CHCH3COR group were also shown to be present in
      an appreciable concentration. Short C-H...C=O and C-H...O=C distances were found
      in each stable conformation. The result was interpreted on the grounds of C
      H...pi(C=O) and C-H...O hydrogen bonds, which stabilize the geometry of the
      molecule. The ratio of the diastereomeric secondary alcohols produced in the
      nucleophilic addition to cyclo-C6H11CHCH3-CO-R was estimated on the basis of the
      conformer distribution. The calculated result was consistent with the
      experimental data previously reported: the gradual increase in the product ratio
      (major/minor) along the series was followed by a drop at R = tBu. The energy of
      the diastereomeric transition states in the addition of LiH to cyclo-C6H11CHCH3
      CO-R was also calculated for R = Me and tBu. The product ratio did not differ
      significantly in going from R = Me to tBu in the case of the aliphatic ketones.
      This is compatible with the above result calculated on the basis of the conformer
      distribution. Thus, the mechanism of the pi-facial selection can be explained in
      terms of the simple premise that the geometry of the transition state resembles
      the ground-state conformation of the substrates and that the nucleophilic reagent
      approaches from the less-hindered side of the carbonyl pi face.

PMID- 17441129
TI  - Self-assembled aggregates and molecular bilayer films of a double-chain fullerene
      lipid: structure and electrochemistry.
AB  - The self-aggregation behavior of C60 fullerenes that bear two octadecyl chains
      (lipid 1) as well as the structures and electrochemical properties of cast films
      of 1 are described. We also examined the self-aggregation behavior in organic
      solvents of three previously reported compounds: C60 with three each of hexadecyl
      (lipid 2), tetradecyl (lipid 3), or dodecyl (lipid 4) chains. The fullerene
      lipids in alcohols spontaneously formed spherical aggregates, whose diameters are
      related to the alkyl-chain lengths, concentrations of the fullerene lipids, and
      the solvent polarity. The morphologies of the aggregates showed temperature
      dependence. Cast films of 1 formed multimolecular bilayer structures that undergo
      a phase transition typical of lipid bilayer membranes. The electrochemistry of
      cast films of 1 on an electrode in aqueous medium exhibits temperature
      dependence.

PMID- 17441130
TI  - Rhodium-catalyzed cascade reaction of 1,6-enynes involving addition, cyclization,
      and beta-oxygen elimination.
AB  - The reaction of arylboronic acids with 1,6-enynes that contain an allylic ether
      moiety is catalyzed by a rhodium(I) complex to produce cyclopentanes with a
      tetrasubstituted exo olefin and a pendant vinyl group. The reaction is initiated
      by the regioselective addition of an arylrhodium(I) species to the carbon-carbon
      triple bond of the 1,6-enyne. The resulting alkenylrhodium(I) compound
      subsequently undergoes intramolecular carborhodation of the allylic double bond
      in a 5-exo-trig mode. Beta elimination of the methoxy group affords the
      cyclization product and the catalytically active methoxorhodium(I) species. The
      use of alkyl Grignard reagents instead of arylboronic acids as organometallic
      nucleophiles was also examined.

PMID- 17441131
TI  - Titanium and zirconium complexes with non-salicylaldimine-type imine-phenoxy
      chelate ligands: syntheses, structures, and ethylene-polymerization behavior.
AB  - New Ti and Zr complexes that bear imine-phenoxy chelate ligands, [{2,4-di-tBu-6
      (RCH=N)-C6H4O}2MCl2] (1: M = Ti, R = Ph; 2: M = Ti, R = C6F5; 3: M = Zr, R = Ph;
      4: M = Zr, R = C6F5), were synthesized and investigated as precatalysts for
      ethylene polymerization. 1H NMR spectroscopy suggests that these complexes exist
      as mixtures of structural isomers. X-ray crystallographic analysis of the adduct
      1HCl reveals that it exists as a zwitterionic complex in which H and Cl are
      situated in close proximity to one of the imine nitrogen atoms and the central
      metal, respectively. The X-ray molecular structure also indicates that one imine
      phenoxy group with the syn C=N configuration functions as a bidentate ligand,
      whereas the other, of the anti C=N form, acts as a monodentate phenoxy ligand.
      Although Zr complexes 3 and 4 with methylaluminoxane (MAO) or [Ph3C]+ [B(C6F5)4]
      /AliBu3 displayed moderate activity, the Ti congeners 1 and 2, in association
      with an appropriate activator, catalyzed ethylene polymerization with high
      efficiency. Upon activation with MAO at 25 degrees C, 2 displayed a very high
      activity of 19900 (kg PE) (mol Ti)(-1) h(-1), which is comparable to that for
      [Cp2TiCl2] and [Cp2ZrCl2], although increasing the polymerization temperature did
      result in a marked decrease in activity. Complex 2 contains a C6F5 group on the
      imine nitrogen atom and mediated nonliving-type polymerization, unlike the
      corresponding salicylaldimine-type complex. Conversely, with [Ph3C]+ [B(C6F5)4]
      /AliBu3 activation, 1 exhibited enhanced activity as the temperature was
      increased (25-75 degrees C) and maintained very high activity for 60 min at 75
      degrees C (18740 (kg PE) (mol Ti)(-1) h(-1)). 1H NMR spectroscopic studies of the
      reaction suggest that this thermally robust catalyst system generates an amine
      phenoxy complex as the catalytically active species. The combinations 1/[Ph3C]+
      [B(C6F5)4]-/AliBu3 and 2/MAO also worked as high-activity catalysts for the
      copolymerization of ethylene and propylene.

PMID- 17441132
TI  - Shape-dependent catalytic activity of silver nanoparticles for the oxidation of
      styrene.
AB  - Metal nanoparticles with different shapes have different crystallographic faces.
      It is therefore of interest to study the effect of the shape of metal
      nanoparticles on their catalytic activity in various organic and inorganic
      reactions. Truncated triangular silver nanoplates with well-defined planes were
      synthesized by a simple solvothermal approach. The activity of these truncated
      triangular silver nanoparticles was compared with that of cubic and near
      spherical silver nanoparticles in the oxidation of styrene in colloidal solution.
      It was found that the crystal faces of silver nanoparticles play an essential
      role in determining the catalytic oxidation properties. The silver nanocubes had
      the {100} crystal faces as the basal plane, whereas truncated triangular
      nanoplates and near-spherical nanoparticles predominantly exposed the most-stable
      {111} crystal faces. As a result, the rate of the reaction over the nanocubes was
      more than 14 times higher than that on nanoplates and four times higher than that
      on near-spherical nanoparticles.

PMID- 17441133
TI  - Synthesis of murisolin, (15R, 16R, 19R, 20S)-murisolin A, and (15R, 16R, 19S,
      20S)-16,19-cis-murisolin and their inhibitory action with bovine heart
      mitochondrial complex I.
AB  - The asymmetric total synthesis of murisolin, (15R, 16R, 19R, 20S)-murisolin A,
      and (15R, 16R, 19S, 20S)-16,19-cis-murisolin was performed by using an epoxy
      alcohol as a versatile chiral building block for synthesizing the stereoisomers
      of mono-THF annonaceous acetogenins. The inhibitory activity of these murisolin
      compounds was examined with bovine heart mitochondrial complex I, and they showed
      almost the same activity.

PMID- 17441136
TI  - Total synthesis of lactacystin and salinosporamide A.
AB  - Lactacystin and salinosporamide A are fascinating molecules with regard to both
      their chemical structures and biological activities. These naturally occurring
      compounds are potent and selective proteasome inhibitors. The molecular
      structures are characterized by their densely functionalized gamma-lactam cores.
      The structure and biological properties of these two compounds are attracting the
      attention of many chemists as challenging synthetic targets. We discuss their
      synthetic strategies in this review.

PMID- 17441137
TI  - Structural and magnetic study of N2, NO, NO2, and SO2 adsorbed within a flexible
      single-crystal adsorbent of [Rh2(bza)4(pyz)]n.
AB  - The crystalline one-dimensional compound, [Rh(II)2(bza)4(pyz)]n (1) (bza =
      benzoate, pyz = pyrazine) demonstrates gas adsorbency for N2, NO, NO2, and SO2.
      These gas-inclusion crystal structures were characterized by single-crystal X-ray
      crystallography as 1 x 1.5 N2 (298 K), 1 x 2.5 N2 (90 K), and 1 x 1.95 NO (90 K)
      under forcible adsorption conditions and 1 x 2 NO2 (90 K) and 1 x 3 SO2 (90 K)
      under ambient pressure. Crystal-phase transition to the P1 space group that
      correlates with gas adsorption was observed under N2, NO, and SO2 conditions. The
      C2/c space group was observed under NO2 conditions without phase transition. All
      adsorbed gases were stabilized by the host lattice. In the N2, NO, and SO2
      inclusion crystals at 90 K, short interatomic distances within van der Waals
      contacts were found among the neighboring guest molecules along the channel. The
      adsorbed NO molecules generated the trans-NO...NO associated dimer with short
      intermolecular contacts but without the conventional chemical bond. The magnetic
      susceptibility of the NO inclusion crystal indicated antiferromagnetic
      interaction between the NO molecules and paramagnetism arising from the NO
      monomer. The NO2 inclusion crystal structure revealed that the gas molecules were
      adsorbed in the crystal in dimeric form, N2O4.

PMID- 17441138
TI  - Columnar mesophase formation of cyclohexa-m-phenylene-based macrocycles.
AB  - Two novel discotic macrocycles, substituted cyclohexa-m-phenylene (CHP) and cyclo
      3,6-trisphenanthrylene (CTP), and the linear oligomer 3,3':6',3''-terphenanthrene
      (TP) as a model substance have been synthesized by repetitive cross-coupling
      reactions. To correlate the molecular design with the supramolecular architecture
      and the established macroscopic order, 2D wide-angle X-ray scattering experiments
      were performed on mechanically extruded filaments. At room temperature in their
      crystalline phases, all three compounds revealed columnar assemblies in which the
      macrocycles self-organized by pi-stacking interactions. The degree of macroscopic
      order was found to depend upon the planarity and stiffness of the aromatic core.
      The flexible CHP ring showed a poor macroscopic order of the columnar structures
      and a low isotropization temperature, whereas the more-planar, less-flexible CTP
      self-assembled into well-defined superstructures. The larger pi-stacking area and
      the more-pronounced intermolecular interactions for CTP led to the formation of a
      mesophase over a very large temperature range. The surprising columnar
      organization of the "open" TP system was explained by back-folding of the
      molecule into a ringlike structure.

PMID- 17441140
TI  - Superoxide compounds of the large pseudo-alkali-metal ions tetramethylammonium, 
      phosphonium, and -arsonium.
AB  - Compounds of the three large cations tetramethylammonium, tetramethylphosphonium,
      and tetramethylarsonium with the superoxide radical anion were synthesized by
      either metathesis or ion exchange in liquid ammonia. They were obtained from
      concentrated solutions as ammoniates in the form of long needle-shaped single
      crystals. [N(CH3)4]-(O2)3NH3 crystallizes in the monoclinic crystal system,
      whereas the two compounds [E(CH3)4](O2)2NH3 (E = P, As) are isostructural and
      belong to the orthorhombic crystal system. The cation-anion packing in all three
      crystal structures is related to the sodium chloride structure. All structures
      contain hydrogen bonds between the ammonia molecules and between ammonia and the
      superoxide. The solvent of crystallization was easily released from the crystals
      upon complete removal of the solvent from the reaction vessel, leading to
      polycrystalline samples. The Raman spectra of all three solvent-free compounds
      show the symmetric stretching mode of the superoxide ion at about 1123 cm(-1).
      The desolvated [N(CH3)4](O2) was investigated by powder X-ray diffraction, and
      the crystal structure was solved by ab initio simulated annealing methods by
      using rigid-body models of the constituent molecular ions. The superoxide ion
      shows rotational disorder. The magnetic susceptibility of tetramethylammonium
      superoxide follows the Curie-Weiss law with a high-temperature effective magnetic
      moment of 1.66(3) muB and a paramagnetic Curie temperature of theta = -13(6) K.
      Complementary electron paramagnetic resonance spectroscopy revealed that the
      average g factor is temperature-dependent. It decreased from 2.15 at 10 K to 1.66
      at 100 K, possibly due to the onset of rotational motion of the superoxide ion
      and in accordance with the lower-than-expected effective magnetic moment.

PMID- 17441139
TI  - Synthesis and bioimaging of positron-emitting 15O-labeled 2-deoxy-D-glucose of
      two-minute half-life.
AB  - In positron emission tomography (PET), which exploits the affinity of a
      radiopharmaceutical for the target organ, a systematic repertoire of oxygen-15
      labeled PET tracers is expected to be useful for bioimaging owing to the ubiquity
      of oxygen atoms in organic compounds. However, because of the 2-min half-life of
      15O, the synthesis of complex biologically active 15O-labeled organic molecules
      has not yet been achieved. A state-of-the-art synthesis now makes available an
      15O-labeled complex organic molecule, 6-[15O]-2-deoxy-D-glucose. Ultrarapid
      radical hydroxylation of 2,6-dideoxy-6-iodo-D-glucose with molecular oxygen
      labeled with 15O of two-minute half-life provided the target 15O-labeled
      molecule. The labeling reaction with 15O was complete in 1.3 min, and the entire
      operation time starting from the generation of 15O-containing dioxygen by a
      cyclotron to the purification of the labeled sugar was 7 min. The labeled sugar
      accumulated in the metabolically active organs as well as in the bladder of mice
      and rats. 15O-labeling offers the possibility of repetitive scanning and the use
      of multiple PET tracers in the same body within a short time, and hence should
      significantly expand the scope of PET studies of small animals.

PMID- 17441141
TI  - Toward electrochemically controllable tristable three-station [2]catenanes.
AB  - Encouraged by the prospect of producing an electrochemical, color-switchable red
      green-blue (RGB) dye compound, we have designed, synthesized, and characterized
      two three-station [2]catenanes. Both are composed of macrocyclic polyethers
      containing three pi-electron-rich stations, which act as recognition sites for a
      pi-electron-deficient tetracationic cyclophane. The molecular structures of the
      two three-station [2]catenanes were characterized fully by mass spectrometry and
      1H NMR spectroscopy. To anticipate the relative occupancies of the three stations
      in each [2]catenane by the cyclophane, model compounds with the same
      constitutions in the vicinity of the stations were synthesized. The relative
      ground-state populations of the three stations occupied in both [2]catenanes were
      estimated from the thermodynamic parameters for 1:1 complexes between all these
      model compounds and the cyclophane, obtained from isothermal titration
      calorimetry (ITC). The electrochemical and electromechanical properties of the
      three-station [2]catenanes were analyzed by cyclic voltammetry (CV), differential
      pulse voltammetry (DPV), and spectroelectrochemistry (SEC). The first three
      station [2]catenane was found to behave like a bistable system, whereas the
      second can be described as a quasi-tristable system.

PMID- 17441143
TI  - Spin-crossover physical gels: a quick thermoreversible response assisted by
      dynamic self-organization.
AB  - Iron(II) triazolate coordination polymers with lipophilic sulfonate counterions
      with alkyl chains of different lengths have been synthesized. In hydrocarbon
      solvents, these polymers formed a physical gel and showed a thermoreversible spin
      transition upon the sol-gel phase transition. The formation of a hydrogen-bonding
      network between the triazolate moieties and sulfonate ions, bridged by water
      molecules, was found to play an important role in the spin-crossover event. The
      spin-transition temperature was tuned over a wide range by adding a small amount
      of 1-octanol, a scavenger for hydrogen-bonding interactions. This additive was
      essential for the iron(II) species to adopt a low-spin state. Compared with
      nongelling references in aromatic solvents, the spin-crossover physical gels are
      characterized by their quick thermal response, which is due to a rapid
      restoration of the hydrogen-bonding network, possibly because of a dynamic
      structural ordering through an enhanced lipophilic interaction of the self
      assembling components in hydrocarbon solvents.

PMID- 17441142
TI  - Thermodynamic parameters for the association of fluorinated benzenesulfonamides
      with bovine carbonic anhydrase II.
AB  - This paper describes a calorimetric study of the association of a series of seven
      fluorinated benzenesulfonamide ligands (C6H(n)F(5-n)SO2NH2) with bovine carbonic
      anhydrase II (BCA). Quantitative structure-activity relationships between the
      free energy, enthalpy, and entropy of binding and pKa and log P of the ligands
      allowed the evaluation of the thermodynamic parameters in terms of the two
      independent effects of fluorination on the ligand: its electrostatic potential
      and its hydrophobicity. The parameters were partitioned to the three different
      structural interactions between the ligand and BCA: the Zn(II) cofactor
      sulfonamide bond (approximately 65% of the free energy of binding), the hydrogen
      bonds between the ligand and BCA (approximately 10%), and the contacts between
      the phenyl ring of the ligand and BCA (approximately 25%). Calorimetry revealed
      that all of the ligands studied bind in a 1:1 stoichiometry with BCA; this result
      was confirmed by 19F NMR spectroscopy and X-ray crystallography (for complexes
      with human carbonic anhydrase II).

PMID- 17441144
TI  - Malyngamide X: the first (7R)-lyngbic acid that connects to a new tripeptide
      backbone from the Thai sea hare Bursatella leachii.
AB  - Malyngamide X (1), the first (7R)-lyngbic acid connected to a new tripeptide
      backbone, was isolated from the Thai sea hare Bursatella leachii. The gross
      structure of 1 was established on the basis of 1D and 2D NMR and mass
      spectroscopic data. Combination of the NMR spectroscopic experiments with alpha
      methoxy-alpha-(trifluoromethyl)phenylacetic acid esters, 2,2,2-trifluoro-1-(9
      anthryl)ethanol chiral solvating agent, and molecular mechanics of 1 and the
      synthetic molecular fragments allowed us to determine the absolute
      stereochemistry of all six stereogenic centers without hydrolytic degradation of
      the compound. Compound 1 displayed moderate cytotoxic, antitubercular, and
      antimalarial properties.

PMID- 17441145
TI  - Enantioselective synthesis of 3,4-dihydropyran-2-ones by domino Michael addition
      and lactonization with new asymmetric organocatalysts: cinchona-alkaloid-derived
      chiral quaternary ammonium phenoxides.
AB  - Chiral quaternary ammonium phenoxides were readily prepared from commercially
      available cinchona alkaloids and proved to be useful new asymmetric
      organocatalysts. Among various chiral quaternary ammonium phenoxides, a
      cinchonidine-derived catalyst that bears both a sterically hindered N1-9
      anthracenylmethyl group and a strongly electron withdrawing 9-O-3,5
      bis(trifluoromethyl)benzyl group were found to be highly effective for the
      Michael addition of ketene silyl acetals (derived from phenyl carboxylates) and
      alpha,beta-unsaturated ketones followed by lactonization. Optically active 3,4
      dihydropyran-2-one derivatives were obtained in high yields with excellent
      control of enantio- and diastereoselectivity. This catalyst can be handled in air
      and stored at room temperature in a sealed bottle without decomposition for at
      least one month.

PMID- 17441146
TI  - Toward the total synthesis of onchidin, a cytotoxic cyclic depsipeptide from a
      mollusc.
AB  - The total synthesis of onchidin (1), a cytotoxic, C2-symmetric cyclic
      decadepsipeptide from a marine mollusc, according to the published structure, is
      described. A novel beta-amino acid, (2S,3S)-3-amino-2-methyl-7-octynoic acid
      (AMO), was efficiently prepared in high yield with high diastereo- and
      enantioselectivity based on a catalytic asymmetric three-component Mannich-type
      reaction with a chiral zirconium catalyst. The formation of sterically
      unfavorable N-methyl amide and hindered ester bonds were successfully
      demonstrated, and final macrocyclization was achieved at a secondary-amide site.
      Completion of the synthesis of 1 suggested that a revision of the structure of
      the natural product is required. Two diastereomers were also synthesized as
      candidates for the actual structure of onchidin. Furthermore, efficient solid
      phase methods were employed for the combinatorial synthesis of other derivatives
      to clarify the real structure of onchidin. The solid-phase assembly of a
      pentadepsipeptide containing all the building blocks was established followed by
      dimeric cyclization in solution.

PMID- 17441147
TI  - Separation of semiconducting single-walled carbon nanotubes by using a long-alkyl
      chain benzenediazonium compound.
AB  - We designed and synthesized 4-dodecyloxybenzenediazonium tetrafluoroborate (1),
      which preferentially reacts with metallic single-walled carbon nanotubes (SWNTs)
      by kinetic control. We first determined the suitable experimental conditions for
      the preferential reaction of 1 with individually dissolved SWNTs by monitoring
      the decrease in absorbance for the metallic SWNT in the range of 400-650 nm in
      the absorption spectrum of the SWNTs. The reacted SWNTs were thoroughly rinsed
      with THF to obtain THF-insoluble SWNTs. The Raman spectrum of the THF-insoluble
      SWNTs showed a strong peak near 180 cm(-1), which corresponds to a semiconducting
      breathing band. The metallic breathing bands (approximately 220 cm(-1)) and Breit
      Wingner-Fano (BWF) modes (1520 cm(-1)) corresponding to the metallic SWNTs were
      much weaker than those of the pristine SWNTs. We also confirmed that metallic
      peaks in the range of 400-650 nm in the absorption spectrum of THF-insoluble
      SWNTs that were individually dissolved in an aqueous micelle of sodium cholate
      were almost nondetectable. All the results indicate that the THF-insoluble SWNTs
      are semiconducting.

PMID- 17441148
TI  - Bismuth- and hafnium-catalyzed hydroamination of vinyl arenes with sulfonamides,
      carbamates, and carboxamides.
AB  - Catalytic intermolecular hydroamination of vinyl arenes is described. Our initial
      investigation revealed that a Bi(OTf)3/[Cu(CH3CN)4]PF6 system previously
      developed for catalytic intermolecular hydroamination of 1,3-dienes was suitable
      for hydroamination of a styrene with sulfonamides, but the substrate generality
      of this system was unsatisfactory. Several metals were screened to expand the
      substrate scope, and a new Hf(OTf)4/[Cu(CH3CN)4]PF6 system was determined to be
      highly suitable. The combination of Hf(OTf)4 and [Cu(CH3CN)4]PF6 efficiently
      promoted the hydroamination of various vinyl arenes, including less-reactive
      vinyl arenes with electron-withdrawing groups. This strategy was applied to
      sulfonamides, carbamates, and carboxamides, and products were obtained in up to
      99% yield with 0.3-10 mol % catalyst loading.

PMID- 17441149
TI  - Osmium complexes with tridentate 6-pyrazol-3-yl 2,2'-bipyridine ligands: coarse
      tuning of phosphorescence from the red to the near-infrared region.
AB  - We have prepared and characterized a series of osmium complexes
      [Os2(CO)4(fpbpy)2] (1), [Os(CO)(fpbpy)2] (2), and [Os(fpbpy)2] (3) with
      tridentate 6-pyrazol-3-yl 2,2'-bipyridine chelating ligands. Upon the
      transformation of complex 2 into 3 through the elimination of the CO ligand, an
      extremely large change in the phosphorescence wavelength from 655 to 935 nm was
      observed. The results are rationalized qualitatively by the strong pi-accepting
      character of CO, which lowers the energy of the osmium d(pi) orbital, in
      combination with the lower degree of pi conjugation in 2 owing to the absence of
      one possible pyridine-binding site. As a result, the energy gap for both
      intraligand pi-pi* charge transfer (ILCT) and metal-to-ligand charge transfer
      (MLCT) is significantly greater in 2. Firm support for this explanation was also
      provided by the time-dependent DFT approach, the results of which led to the
      conclusion that the S0-->T1 transition mainly involves MLCT between the osmium
      center and bipyridine in combination with pyrazolate-to-bipyridine 3pi-pi* ILCT.
      The relatively weak near-infrared emission can be rationalized tentatively by the
      energy-gap law, according to which the radiationless deactivation may be governed
      by certain low-frequency motions with a high density of states. The information
      provided should allow the successful design of other emissive tridentate metal
      complexes, the physical properties of which could be significantly different from
      those of complexes with only a bidentate chromophore.

PMID- 17441150
TI  - Manipulating the through-space spin-spin interaction of organic radicals in the
      confined cavity of a self-assembled cage.
AB  - We show a new approach to manipulating the through-space spin-spin interaction by
      utilizing the confined cavity of a self-assembled M6L4 coordination cage. The
      coordination cage readily encapsulates stable organic radicals in solution, which
      brings the spin centers of the radicals closer to each other. In sharp contrast
      to the fact that the radical in solution in the absence of the cage is in a
      doublet state, in the presence of the cage through-space spin-spin interaction is
      induced through cage-encapsulation effects in solution as well as in the solid
      state, resulting in the triplet state of the complex. These results were
      confirmed by ESR spectroscopy and X-ray crystallography. The quantity of triplet
      species generated by encapsulation in the cage increases with increasing affinity
      of the radicals to the cage. We estimated the affinity between several types of
      guests and the cage in solution by cyclic voltammetry. We also demonstrate that
      the through-space interaction of organic radicals within the self-assembled
      coordination cage can be controlled by external stimuli such as heat or pH.

PMID- 17441151
TI  - Multi-input-multi-output molecular response system based on dynamic redox
      behavior of hexaphenylethane-type electron donors with the
      tetrahydrophenanthrazepine skeleton: strong chiroptical signals through the
      transmission of point chirality to helicity.
AB  - The title heterocyclic donors undergo reversible C-C bond formation/cleavage upon
      electron transfer (dynamic redox behavior). The helical sense in both neutral and
      cationic states is interconvertible by facile ring flipping. The pi-type
      asymmetric center on the azepine nitrogen atom induces a significant degree of
      diasteromeric preference, thus endowing strong CD activity based on exciton
      coupling. Chiroptical properties could be modified not only by redox reactions
      but also by heat and protonation. The present redox pairs can serve as
      unprecedented three-way-input (e, H+, delta) and two-way-output (UV/Vis, CD)
      response systems.

PMID- 17441152
TI  - Stable P-heterocyclic carbenes: scope and limitations.
AB  - The conjugate acids (PHCH+s) of P-heterocyclic carbenes (PHCs) are prepared by
      formal [3+2] cycloaddition of a 1,3-diphosphaallyl or 1,3-phosphinophosphenium
      cation with various nitriles. The effect of the phosphorus substituent on the
      fate of the cyclization and on that of the counteranion and base in the
      subsequent deprotonation reaction are reported. Two PHCs that are indefinitely
      stable in the solid state are described. In solution, one of them, made from
      acetonitrile, undergoes a facile [3+2] cycloreversion, whereas the other, based
      on dimethyl cyanamide, is stable, presumably owing to its zwitterionic structure,
      which involves a tricoordinate pentavalent phosphorus atom. The reactivity of
      PHCs is strongly driven by the high electrophilicity of the phosphorus centers,
      as demonstrated by their reactivity with water and benzaldehyde. Although both
      PHCs reported in this paper are direct analogues of the least-basic NHCs, their
      basicity is comparable to those of the more strongly basic NHCs (as determined by
      comparison of the carbonyl stretching frequencies of their corresponding cis
      [RhCl-(CO)2(L)] complexes).

PMID- 17441153
TI  - Donor-bound glycosylation for various glycosyl acceptors: bidirectional solid
      phase semisynthesis of vancomycin and its derivatives.
AB  - The glycosidation of a polymer-supported glycosyl donor, N
      phenyltrifluoroacetimidate, with various glycosyl acceptors is reported. The
      application of the polymer-supported N-phenyltrifluoroacetimidate is demonstrated
      in the synthesis of vancomycin derivatives. 2-O-[2-(azidomethyl)benzoyl]glycosyl
      imidate was attached to a polymer support at the 6-position by a phenylsulfonate
      linked with a C13 alkyl spacer. Solid-phase glycosidation with a vancomycin
      aglycon, selective deprotection of the 2-(azidomethyl)benzoyl group, and
      glycosylation of the resulting 2-hydroxy group with a vancosamine unit were
      performed. Nucleophilic cleavage from the polymer support with acetate, chloride,
      azido, and thioacetate ions provided vancomycin derivatives in pure form after
      simple purification. The semisynthesis of vancomycin was achieved by deprotection
      of the acetate derivative.

PMID- 17441154
TI  - Rh(I)-catalyzed bimolecular cyclization between two different 1,5-bisallenes: a
      combinatorial one-step approach to heterosteroids and mechanistic implications.
AB  - In this paper, a bimolecular-cyclization reaction between two different
      bis(allene)s with at least one heteroatom as the tether under the catalysis of
      trans-[RhCl(CO)(PPh3)2] is described. This protocol provides an efficient entry
      to different heterocyclic 18,19-norsteroid-like scaffolds. The tricyclic product
      was formed highly selectively from the cyclization reaction of bis(2,3
      butadienyl)sulfide with dimethyl 2-bis(2',3'-butadienyl)malonate, which sheds
      light on the mechanism involving the metalla-[4.3.0]-bicyclic intermediate formed
      by the cyclometallation of the terminal and the internal C=C bonds of each of the
      two allene moieties in 2-bis(2',3'-butadienyl)malonate.

PMID- 17441156
TI  - Progress in polydiacetylene nanowires by self-assembly and selfpolymerization.
AB  - In recent years, there has been immense interest in studying nanoscale aggregate
      structures derived from various polydiacetylenes (PDAs). The motivation for this
      is not only to understand the fundamental aggregate structures at different
      scales, but also to explore their potential for future technological
      applications. PDAs have been made sensitive to external stimuli such as light and
      chemical entities by incorporating a spectroscopically active moiety or a
      receptor unit as the head group of the PDA molecule. This makes them suitable for
      applications such as sensing and actuating. Furthermore, owing to the
      delocalization of pi-conjugated electrons, PDAs have been exploited as good
      candidates for organic nonlinear optical materials. This Focus Review highlights
      some of the instructive work done by various groups to develop well-defined one
      dimensional assembly systems with a highly structural aspect ratio, which can be
      directly imaged by microscopic techniques.

PMID- 17441157
TI  - Supramolecular tilt chirality derived from symmetrical benzene molecules:
      handedness of the 2(1) helical assembly.
AB  - Achiral molecules can form aggregates with chirality. This depends on the
      relative position of the molecules, in other words, the tilt of the molecules (so
      called supramolecular tilt chirality). In this paper, we describe supramolecular
      chirality appearing in a 2(1) column composed of symmetrical benzene molecules,
      which is formed in the host cavity of inclusion crystals of cholic acid.
      Moreover, we determined the handedness, that is, right or left, of the 2(1)
      helical column of benzene on the basis of the molecular tilt. Determination of
      the 2(1) helical handedness was performed on assemblies of other benzene
      derivatives in cholic acid crystals and benzene assemblies in other host
      frameworks selected from the Cambridge Structural Database. Finally, we
      demonstrated complementarity of the handedness between the 2(1) symmetrical host
      framework of cholic acid and the benzene column.

PMID- 17441158
TI  - Highly efficient non-palladium-catalyzed controlled synthesis and X-ray analysis
      of functionalized 1,2-diaryl-, 1,2,3-triaryl-, and 1,2,3,4-tetraarylbenzenes.
AB  - A general, two-step, highly efficient synthesis of 1,2-diaryl-, 1,2,3-triaryl-,
      and 1,2,3,4-tetraarylbenzenes from simple stitching of alpha-oxo-ketene-S,S
      acetals and active methylene compounds via a lactone intermediate is described.
      This procedure offers easy access to highly functionalized arylated benzenes that
      contain sterically demanding groups in good to excellent yields. The novelty of
      the procedure lies in the construction of aromatic compounds with the desired
      conformational flexibility along the molecular axis in a transition-metal-free
      environment through easily accessible precursors. Crystal analysis of these
      arylated benzene scaffolds showed that the peripheral aryl rings are arranged in
      a propeller-like fashion with respect to the central benzene ring. Examination of
      the crystal packing in the structure of a 1,2,3,4-tetraarylbenzene revealed an
      N...pi interaction between molecules related by a two-fold screw axis running in
      the direction of the a axis. Interestingly, the repeating array of N...pi
      interactions around the axis of this 1,2,3,4-tetraarylbenzene forces the
      molecules into a helical pattern.

PMID- 17441159
TI  - Construction of robust ruthenium(salen)(CO) complexes and asymmetric
      aziridination with nitrene precursors in the form of azide compounds that bear
      easily removable N-sulfonyl groups.
AB  - We synthesized new Ru(salen)(CO) complexes of high durability and achieved
      aziridination with good to excellent enantioselectivity by using azide compounds
      that contain an easily removable N-sulfonyl group, such as the 2
      (trimethylsilyl)ethanesulfonyl group, as a nitrene precursor. Aziridination of
      less-reactive alpha,beta-unsaturated esters (and amides) proceeded with excellent
      enantioselectivities, from which it is inferred that an electrophilic species is
      the active species of this reaction. The present asymmetric aziridination
      provides a useful tool for introducing optically active nonprotected amine
      groups.

PMID- 17441160
TI  - Catalytic asymmetric epoxidation of alpha,beta-unsaturated esters with chiral
      yttrium-biaryldiol complexes.
AB  - The full details of the asymmetric epoxidation of alpha,beta-unsaturated esters
      catalyzed by yttrium complexes with biaryldiol ligands are described. An yttrium
      biphenyldiol catalyst, generated from Y(OiPr)3-biphenyldiol ligand
      triphenylarsine oxide (1:1:1), is suitable for the epoxidation of various
      alpha,beta-unsaturated esters. With this catalyst, beta-aryl alpha,beta
      unsaturated esters gave high enantioselectivities and good yields (< or = 99%
      ee). The reactivity of this catalyst is good, and the catalyst loading could be
      decreased to as little as 0.5-2 mol % (the turnover number was up to 116), while
      high enantiomeric excesses were maintained. For beta-alkyl alpha,beta-unsaturated
      esters, an yttrium-binol catalyst, generated from Y(OiPr)3-binol ligand
      triphenylphosphine oxide (1:1:2), gave the best enantioselectivities (< or = 97%
      ee). The utility of the epoxidation reaction was demonstrated in an efficient
      synthesis of (-)-ragaglitazar, a potential antidiabetes agent.

PMID- 17441161
TI  - Shape- and functionality-controlled organization of TiO2-porphyrin-C60 assemblies
      for improved performance of photochemical solar cells.
AB  - Shape- and functionality-controlled organization of porphyrin derivatives-C60
      supramolecular assemblies using TiO2 nanotubes and nanoparticles has been
      achieved for the development of photochemical solar cells. The differences in the
      efficiency of light-energy conversion of these solar cells are explained on the
      basis of the geometrical orientation of the porphyrins with respect to the TiO2
      surface and the supramolecular complex formed with C60. The maximum photon
      conversion efficiency (IPCE) of 60% obtained with TiO2 nanotube architecture is
      higher than the value obtained with nanoparticle architecture. The results
      presented in this study show the importance of substrate morphology in promoting
      electron transport within the mesoscopic semiconductor film.

PMID- 17441162
TI  - Diels-Alder reactions of novel (1'-arylallylidene)cyclopropanes with
      heterodienophiles.
AB  - Palladium-catalyzed cross-coupling of various aryl iodides with
      bicyclopropylidene provided isolable (1'-arylallylidene)cyclopropanes, which
      reacted with a number of carbonyl compounds in the presence of Eu(fod)3 under
      high pressure to furnish oxaspiro[2.5]octene derivatives in moderate to good
      yields (22-69%). The reactions of the allylidenecyclopropanes with two azo
      compounds as dienophiles afforded diazaspiro[2.5]octenes in high yields (82 and
      99%) even at ambient pressure. When treated with nitrosobenzene, two of the
      allylidenecyclopropanes gave the Diels-Alder adducts in up to 83 and 40% yield.
      2,5-Diiodo-p-xylene coupled twice with bicyclopropylidene, and the product
      underwent a twofold Diels-Alder reaction with nitrosobenzene to produce the
      bis(spirocyclopropaneoxazine) derivative in 88% yield. This overall
      transformation can be brought about in a one-pot, two-step operation by addition
      of the nitrosoarene to the reaction mixture immediately after formation of the
      allylidenecyclopropanes to furnish various 5-oxa-4-azaspiro[2.5]oct-7-ene
      derivatives in 22-77% yield. The coupling of methyl bicyclopropylidenecarboxylate
      with 2,6-dimethylphenyl iodide produced a mixture of very stable regioisomeric
      allylidenecyclopropane derivatives in 90% yield. The reaction of this mixture
      with N-phenyltriazolinedione gave a corresponding mixture of the
      spirocyclopropanated heterobicycles in 61% yield.

PMID- 17441163
TI  - Energy landscape of aptamer/protein complexes studied by single-molecule force
      spectroscopy.
AB  - Aptamers are single-stranded nucleic acid molecules selected in vitro to bind to
      a variety of target molecules. Aptamers bound to proteins are emerging as a new
      class of molecules that rival commonly used antibodies in both therapeutic and
      diagnostic applications. With the increasing application of aptamers as molecular
      probes for protein recognition, it is important to understand the molecular
      mechanism of aptamer-protein interaction. Recently, we developed a method of
      using atomic force microscopy (AFM) to study the single-molecule rupture force of
      aptamer/protein complexes. In this work, we investigate further the unbinding
      dynamics of aptamer/protein complexes and their dissociation-energy landscape by
      AFM. The dependence of single-molecule force on the AFM loading rate was plotted
      for three aptamer/protein complexes and their dissociation rate constants, and
      other parameters characterizing their dissociation pathways were obtained.
      Furthermore, the single-molecule force spectra of three aptamer/protein complexes
      were compared to those of the corresponding antibody/protein complexes in the
      same loading-rate range. The results revealed two activation barriers and one
      intermediate state in the unbinding process of aptamer/protein complexes, which
      is different from the energy landscape of antibody/protein complexes. The results
      provide new information for the study of aptamer-protein interaction at the
      molecular level.

PMID- 17441164
TI  - Boomerang-type substitution reaction: reactivity of fullerene epoxides and a
      halofullerenol.
AB  - The C(s)-symmetric fullerene chlorohydrin C60(Cl)(OH)(OOtBu)4 reacts with 4
      dimethylaminopyridine (DMAP) and 1,4-diazabicyclo[2.2.2]octane (DABCO) to yield
      two isomers with the formula C60(O)(OOtBu)4 in good yields. These isomers differ
      with respect to the location of the epoxy functionality. The one from DMAP is
      C(s) symmetric, whereas that from DABCO is C1 symmetric with the epoxy group on
      the central pentagon. Two different mechanisms are proposed to explain the
      chemoselectivity of these reactions. The reaction with DMAP involves single
      electron transfer as the key step; DMAP acts as the electron donor. A combination
      of an oxygen-atom shift and S(N)2'' processes (boomerang substitution) are
      responsible for the formation of isomer with DACBO. Various related reactions
      support the proposed mechanisms. The structures of new fullerene derivatives were
      determined by spectroscopy, single-crystal X-ray analysis, and chemical
      correlation experiments.

PMID- 17441165
TI  - Photoluminescent and liquid-crystalline properties of donor-acceptor-type 2,5
      diarylthiazoles.
AB  - The synthesis of donor-acceptor-type 2,5-diarylthiazoles that bear electron
      donating N,N-dialkylamine and electron-withdrawing cyano groups at the 2- and 5
      position, respectively, were carried out with transition-metal-catalyzed C-H
      arylation reactions developed by us. The compounds were synthesized by the C-H
      arylation of unsubstituted thiazole at the 2-position with a palladium/copper
      catalyst in the presence of tetrabutylammonium fluoride (TBAF) as an activator.
      Further C-H arylation of the 2-arylated thiazole at the 5-position was carried
      out by the palladium-catalyzed reaction in the presence of silver(I) fluoride to
      afford the donor-acceptor-type 2,5-diarylthiazoles with N,N-dialkylamine groups
      of different chain lengths. The UV/Vis absorption, photoluminescence, and
      electrochemical behavior were similar regardless of chain length, whereas liquid
      crystalline behavior and thermal characteristics were found to be dependent on
      the alkyl-chain length. The compounds with N,N-diethylamine or N-butyl-N-methyl
      groups showed a stable liquid-crystalline phase over a wide temperature range as
      well as higher stability to thermal decomposition.

PMID- 17441166
TI  - Easily accessible benzamide-derived P,O ligands (Bphos) for palladium-catalyzed
      carbon-nitrogen bond-forming reactions.
AB  - Easily accessible benzamide-derived hemilabile phosphine ligands were efficiently
      prepared through ortho-directed lithiation of the corresponding N,N
      diethylbenzamide followed by quenching with chlorodialkylphosphines. These
      structurally simple hemilabile ligands were found to be highly effective in
      palladium-catalyzed amination of aryl and heteroaryl chlorides. Various
      sterically congested and functionalized aryl halide substrates were compatible in
      these reaction conditions. By using optimized reaction conditions, remarkable
      catalyst productivity (total turnover number up to 8400) was obtained.

PMID- 17441167
TI  - Synthesis and application of a bidentate ligand based on decafluoro-3-phenyl-3
      pentanol: steric effect of pentafluoroethyl groups on the stereomutation of O
      equatorial C-apical spirophosphoranes.
AB  - 1,1,1,2,2,4,4,5,5,5-Decafluoro-3-phenyl-3-pentanol was prepared by a Cannizzaro
      type disproportionation reaction, and the dimetallated compound was used as a
      bidentate ligand, which is bulkier than the Martin ligand (1,1,1,3,3,3-hexafluoro
      2-phenyl-2-propanol). A P-H spirophosphorane was synthesized by utilizing the new
      bidentate ligand, and the structure of the product was essentially the same as
      that of the P-H phosphorane with Martin ligands. Phosphoranes that exhibit
      reversed apicophilicity (O-equatorial) were also synthesized and could be
      converted into the corresponding stable stereoisomers (O-apical). The crystal
      structures of O-equatorial phosphoranes and the O-apical isomers were slightly
      affected by the steric repulsion of pentafluoroethyl groups. Kinetic measurements
      revealed that the stereomutation of O-equatorial methylphosphorane to the O
      apical isomer was slowed. The activation enthalpy for the stereomutation of the
      former to the latter was higher than that of the phosphorane with Martin ligands
      by 5.1 kcal mol(-1).

PMID- 17441169
TI  - Ratiometric and near-infrared molecular probes for the detection and imaging of
      zinc ions.
AB  - The detection and imaging of Zn2+ in biological samples are of paramount interest
      owing to the role of this cation in physiological functions. This is possible
      only with molecular probes that specifically bind to Zn2+ and result in changes
      in emission properties. A "turn-on" emission or shift in the emission color upon
      binding to Zn2+ should be ideal for in vivo imaging. In this context, ratiometric
      and near-IR probes are of particular interest. Therefore, in the area of
      chemosensors or molecular probes, the design of fluorophores that allow
      ratiometric sensing or imaging in the near-IR region is attracting the attention
      of chemists. The purpose of this Focus Review is to highlight recent developments
      in this area and stress the importance of further research for future
      applications.

PMID- 17441170
TI  - Micro- and nanometer-scale porous, fibrous, and sheet architectures constructed
      by supramolecular assemblies of dipyrrolyldiketones.
AB  - X-ray analysis of some 1,3-dipyrrolyl-1,3-propanediones synthesized from pyrroles
      and malonyl chloride derivatives revealed 1D supramolecular networks formed by N
      H...O=C interactions in the solid state. Micro- and nanometer-scale morphologies
      of porous, fibrous, and sheet structures were fabricated by hydrogen-bonding
      interactions and determined by fine-tuning the substituents and the solvents
      used. Of the unique polymorphs, ordered 2D lamellar sheet structures of the
      derivatives with long alkyl chains (C16H33, C14H29, and so on) were constructed
      by van der Waals hydrophobic effects between aliphatic chains as well as hydrogen
      bonding.

PMID- 17441171
TI  - Chiral ruthenium-allenylidene complexes that bear a fullerene cyclopentadienyl
      ligand: synthesis, characterization, and remote chirality transfer.
AB  - Ruthenium complexes that bear both a fullerene and an allenylidene ligand,
      [Ru(C60Me5)((R)-prophos)=C=C=CR1R2]PF6 (prophos = 1,2
      bis(diphenylphosphanyl)propane), were prepared by the reaction of
      [Ru(C60Me5)Cl((R)-prophos)] and a propargyl alcohol in better than 90% yields,
      and characterized by 1H, 13C, and 31P NMR, IR, and UV/Vis/NIR spectroscopy and
      MS. Cyclic voltammograms of these complexes showed one reversible or irreversible
      reduction wave due to the allenylidene part, and two reversible reduction waves
      due to the fullerene core. Nucleophilic addition of RMgBr or RLi proceeded
      regioselectively at the distal carbon atom of the allenylidene array. The
      reaction took place with a 60:40-95:5 level of diastereoselectivity with respect
      to the original chirality in the (R)-prophos ligand, which is located six atoms
      away from the electrophilic carbon center.

PMID- 17441172
TI  - Synthesis of molecular wires of linear and branched bis(terpyridine)-complex
      oligomers and electrochemical observation of through-bond redox conduction.
AB  - Films of linear and branched oligomer wires of Fe(tpy)2 (tpy = 2,2':6',2''
      terpyridine) were constructed on a gold-electrode surface by the interfacial
      stepwise coordination method, in which a surface-anchoring ligand, (tpy
      C6H4N=NC6H4-S)2 (1), two bridging ligands, 1,4-(tpy)2C6H4 (3) and 1,3,5-(C[triple
      bond]C-tpy)3C6H3 (4), and metal ions were used. The quantitative complexation of
      the ligands and Fe(II) ions was monitored by electrochemical measurements in up
      to eight complexation cycles for linear oligomers of 3 and in up to four cycles
      for branched oligomers of 4. STM observation of branched oligomers at low surface
      coverage showed an even distribution of nanodots of uniform size and shape, which
      suggests the quantitative formation of dendritic structures. The electron
      transport mechanism and kinetics for the redox reaction of the films of linear
      and branched oligomer wires were analyzed by potential-step chronoamperometry
      (PSCA). The unique current-versus-time behavior observed under all conditions
      indicates that electron conduction occurs not by diffusional motion but by
      successive electron hopping between neighboring redox sites within a molecular
      wire. Redox conduction in a single molecular wire in a redox-polymer film has not
      been reported previously. The analysis provided the rate constant for electron
      transfer between the electrode and the nearest redox-complex moiety, k1 (s(-1)),
      as well as that for intrawire electron transfer between neighboring redox-complex
      moieties, k2 (cm2 mol(-1) s(-1)). The strong effect of the electrolyte
      concentration on both k1 and k2 indicates that the counterion motion limits the
      electron-hopping rate at lower electrolyte concentrations. Analysis of the
      dependence of k1 and k2 on the potential gave intrinsic kinetic parameters
      without overpotential effects: (k1(0) = 110 s(-1), k2(0) = 2.6x10(12) cm2 mol(-1)
      s(-1) for [n Fe3], and k1(0) = 100 s(-1), k2(0) = 4.1x10(11) cm2 mol(-1) s(-1)
      for [n Fe4] (n = number of complexation cycles).

PMID- 17441173
TI  - Synthesis of [18,19,21,22-(13)C4]-labeled tautomycin as an NMR probe of protein
      phosphatase inhibitor.
AB  - We have accomplished the synthesis of 13C-labeled tautomycin at the C18, C19,
      C21, and C22 positions starting from 100% [13C]triethylphosphonoacetate for the
      purpose of elucidating the dynamics and conformation of the C17-C26 moiety. NMR
      spectroscopy of 13C-labeled tautomycin revealed strong binding with protein
      phosphatase type 1 and new features in the 13C NMR spectrum, such as the very
      small three-bond coupling constants (2J).

PMID- 17441174
TI  - Novel unsymmetric alpha-diimine nickel(II) complexes: suitable catalysts for
      copolymerization reactions.
AB  - We established a strategy to synthesize novel unsymmetric 2,3-diaza-1,4-dithiane
      ligands. Reaction of [Ni(acac)2] and trityl tetrakis(pentafluorophenyl)borate in
      the presence of these ligands afforded the corresponding salt-type complexes. All
      new compounds were characterized by means of elemental analysis and NMR
      spectroscopy, and the complexes additionally by mass spectroscopy. NMR
      spectroscopic experiments on polymers generated by the symmetric
      ligand/trimethylaluminum catalyst system showed that all products were nearly
      linear, independent of the polymerization conditions. By contrast, polymers
      produced by the unsymmetric ligand/trimethylaluminum catalyst system under
      homopolymerization conditions were branched (15-24 per thousand). Additionally,
      copolymerization experiments with propylene and 1-hexene afforded copolymers with
      a branching level of up to 50 per thousand.

PMID- 17441175
TI  - Ruthenium-catalyzed sequential reactions: deracemization of secondary benzylic
      alcohols.
AB  - The deracemization of secondary benzylic alcohols proceeds successfully by a two
      step process with the appropriate combination of two different ruthenium
      complexes for catalysis in the first oxidation and second reduction steps. The
      sequential catalytic system provides a novel approach to obtaining optically
      active alcohols, including diols, in high yields with excellent
      enantioselectivity (up to 95% ee), in contrast to the conventional kinetic
      resolution of racemic alcohols.

PMID- 17441176
TI  - Synthesis of a stimuli-responsive P-chiral polymer with chiral phosphorus atoms
      and azobenzene moieties in the main chain.
AB  - A reaction of the P-chiral compound (S,S)-1,2-bis(boranato(tert
      butyl)methylphosphino)ethane with an azobenzene derivative gave stimuli
      responsive polymers with P-chiral phosphines in the main chain. This is the first
      example of a stimuli-responsive P-chiral polymer. The polymer isomerized from the
      trans to the cis form upon UV irradiation and reverted to the trans form
      reversibly. The polymer was able to coordinate to platinum, and the resulting
      polymer complex exhibited the Cotton effect owing to the chirality of the
      phosphorus atoms. The structure of the P-chiral polymer obtained could be changed
      reversibly by light and thermal stimuli, and the polymer chain was induced to
      rotate helically when complexed with transition metals through the chiral
      phosphorus atoms.

PMID- 17441177
TI  - An improved ruthenium catalyst for the environmentally benign amination of
      primary and secondary alcohols.
AB  - The N-alkylation of amines in the presence of different ruthenium catalysts
      generated in situ was investigated. Among the various catalysts tested, the
      combination of [Ru3(CO)12] and N-phenyl-2-(dicyclohexylphosphanyl)pyrrole showed
      the best performance. By applying this novel catalyst, a variety of
      functionalized alcohols and amines were converted into the corresponding
      secondary amines in high yield.

PMID- 17441178
TI  - A novel environmentally benign method for the selective oxidation of alcohols to
      aldehydes and ketones.
AB  - In the presence of [Ru(terpyridine)(2,6-pyridinedicarboxylate)], aliphatic and
      benzylic alcohols are oxidized to the corresponding aldehydes or ketones with
      high selectivity by using hydrogen peroxide as the oxidant. There is no need for
      the addition of co-catalysts or organic solvents. By applying an optimized
      reaction protocol, high catalyst productivity (turnover number>10,000) and
      activity (turnover frequency up to 14,800 h(-1)) has been achieved.

PMID- 17441179
TI  - Chemoselective C(sp3)-H bond activation for the preparation of condensed N
      heterocycles.
AB  - Condensed N-heterocycles were prepared by using C-H activation reactions
      catalyzed by Pd(OAc)2 (5 mol %) and (p-tolyl)3P (10 mol %). The key step of these
      ring closures is chemoselective intramolecular C-H activation of the methyl group
      at position 2 of the pyrrole ring. Functionalized 9H-pyrrolo[1,2-a]indoles and
      pyrrolo[1,2-f]phenanthridine derivatives were prepared in good yields. The
      preparation of some complex N-heterocycles by using successive reactions is also
      described.

PMID- 17441182
TI  - Multinuclear silver ethynide supramolecular synthons for the construction of
      coordination networks.
AB  - The invariant appearance of the mu8 coordination mode for the C4(2-) dianion in
      its silver(I) complexes, with four silver(I) atoms attached to each terminal
      ethynide moiety, implies that the Ag4[cap]C[triple bond]C-C[triple bond]C[cap]Ag4
      species may be considered as a new type of supramolecular synthon for the
      construction of 1D, 2D, and 3D coordination polymers. This Focus Review covers
      recent results on the synthesis and structural characterization of silver(I)
      arylethynide and alkylethynide complexes, which established the existence and
      utility of analogous polynuclear supramolecular synthons R-C[triple
      bond]C[cap]Ag(n) (R = aryl or alkyl; n = 4, 5) and Ag(n)[cap]C2-R-C2[cap]Ag(n) (R
      = p-, m-, o-C6H4; n = 4, 5). The interplay of silver-ethynide bonding, which can
      be classified into sigma, pi, and mixed (sigma,pi) types, with argentophilicity,
      pi-pi stacking, and other weak interactions highlights the complexity and
      challenge in building coordination networks of silver ethynide complexes.

PMID- 17441183
TI  - Self-assembly and host-guest chemistry of a 3.5-nm coordination nanotube.
AB  - Upon complexation with Pd(II) ions, precisely designed strandlike ligands with
      two tris(3,5-pyridine) units at both terminals were assembled, with the aid of a
      linear template molecule, into a discrete tubular complex with a length of 3.5
      nm. The high stability and the well-defined structure of the coordination
      nanotube were revealed by NMR spectroscopy, cold-spray ionization MS, and single
      crystal X-ray analysis. Guest lengths were discriminated by the tube: When the
      association of strandlike guest molecules, in which two biphenylene units are
      linked with an (OCH2CH2)n linker, were compared, the tube selectively recognized
      an appropriate guest whose length was comparable to that of the tube.
      Tetrathiafulvalene (TTF)-terminated linear guests were directly oxidized to TTF2+
      in the tube, but reduced stepwise via TTF+ outside the tube.

PMID- 17441184
TI  - Unusual rate acceleration in Bronsted acid catalyzed dehydration reactions: local
      hydrophobic environment in aggregated N-(2,6-diphenylphenyl)-N-mesitylammonium
      pentafluorobenzenesulfonates.
AB  - Bulky diarylammonium pentafluorobenzenesulfonates effectively promote dehydration
      reactions, such as condensation reactions to give esters and the dehydrative
      cyclization of 1,3,5-triketones. In particular, N-(2,6-diphenylphenyl)-N
      mesitylammonium pentafluorobenzenesulfonate shows much higher catalytic activity
      than C6F5SO3H under reaction conditions without the removal of generated water,
      even though the former is a weaker acid. Its crystallization gives an aggregated
      cyclic ion pair, which is composed of two diarylammonium cations, four
      pentafluorobenzenesulfonate anions, and two oxonium cations. This ion pair is
      strongly stabilized by four intermolecular and two intramolecular pi-pi
      attractive interactions and 10 hydrogen bonds. The extremely high catalytic
      activity of N-(2,6-diphenylphenyl)-N-mesitylammonium pentafluorobenzenesulfonate
      in the dehydration reactions may be ascribed to the local hydrophobic environment
      of the tightly aggregated ammonium salts.

PMID- 17441185
TI  - Microporous magnesium and manganese formates for acetylene storage and
      separation.
AB  - Acetylene sorption of microporous metal formates M(HCOO)2 (M = Mg and Mn) was
      investigated. Measurements of acetylene sorption at 196, 275, and 298 K showed a
      Type I isotherm with quick saturation at low pressures, and 50-75 cm3 g(-1)
      uptake at 1.0 atm. The single-crystal X-ray structure analysis of the acetylene
      adsorbed metal formates revealed that acetylene molecules occupy two independent
      positions in the zigzag channels of the frameworks with a stoichiometry of
      M(HCOO)2 x 1/3C2H2, which is consistent with the gas sorption experiments. No
      specific interaction except van der Waals interactions between the adsorbed
      acetylene molecules and the walls of the frameworks was found. Sorption
      properties of other gases, including CO2, CH4, N2, O2, and H2, were also
      investigated. When the temperature was increased to 298 K, the amount of adsorbed
      acetylene was still above 60 cm3 g(-1) for Mg(HCOO)2 and 50 cm3 g(-1) for
      Mn(HCOO)2, whereas the uptake of other gases decreased substantially. The
      microporous metal formates may thus be useful not only for the storage of
      acetylene but also its separation from other gases at room or slightly higher
      temperatures.

PMID- 17441186
TI  - Synthesis and spectroscopic studies of arylethynylsilanes.
AB  - A variety of arylethynylsilanes (Ar-C[triple bond]C-C6H4-C[triple
      bond]C)(n)SiMe(4-n) were prepared successfully by reaction of the corresponding
      chlorosilanes Me(4-n)SiCl(n) with Ar-C[triple bond]C-C6H4-C[triple bond]CM (M =
      Li, MgBr), which was prepared by treatment of ethynyl(diarylethyne)s Ar-C[triple
      bond]C-C6H4-C[triple bond]CH with BuLi or MeMgBr. The ethynyl(diarylethyne)s were
      readily prepared in good yields by the double-elimination method: addition of
      lithium hexamethyldisilazide to a mixture of ArCH2SO2Ph, TMS-C[triple bond]C-C6H4
      CHO, and ClP(O)(OEt)2, followed by desilylation. In the
      tetrakis(arylethynyl)silanes (Ar-C[triple bond]C-C6H4-C[triple bond]C)4Si thus
      prepared, through-space conjugation of four triple bonds on the silicon atom
      emerges as a result of participation of the silicon orbitals in the acetylenic pi
      orbitals. This participation enhances the emissive quantum yields of
      arylethynylsilanes with an increase in the number of arylethynyl moieties on
      silicon: quantum yields of emission (phiF) of 0.72 for (MeOC6H4-C[triple bond]C
      C6H4-C[triple bond]C)4Si, 0.53 for (MeOC6H4-C[triple bond]C-C6H4-C[triple
      bond]C)2SiMe2, and 0.47 for MeO-C6H4-C[triple bond]C-C6H4-C[triple bond]CSiMe3
      were obtained. Although this enhancement effect was also observed in the
      phenylethynylarylsilane (MeOC6H4-C[triple bond]C-C6H4)2SiMe2, the
      bis(arylethynyl)disilane (MeOC6H4-C[triple bond]C-C6H4-C[triple bond]C-SiMe2)2
      exhibited non-enhanced emission.

PMID- 17441187
TI  - Tetrahydrofuran activates fluorescence resonant energy transfer from a cationic
      conjugated polyelectrolyte to fluorescein-labeled DNA in aqueous media.
AB  - A cationic water-soluble conjugated polyelectrolyte, poly[9,9-bis(6''-(N,N,N
      trimethylammonium)hexyl)fluorene-co-alt-2,5-bis(6'-(N,N,N
      trimethylammonium)hexyloxyphenylene) tetrabromide], was synthesized. Fluorescence
      resonant energy transfer (FRET) experiments between the polymer and fluorescein
      labeled single-stranded DNA (ssDNA-Fl) were conducted in aqueous buffer and
      THF/buffer mixtures. Weak fluorescence emission in aqueous buffer was observed
      upon excitation of the polymer, whereas addition of THF turned on the
      fluorescence. Fluorescence self-quenching of ssDNA-Fl in the ssDNA-Fl/polymer
      complexes as well as electron transfer from the polymer to fluorescein may
      account for the low fluorescence emission in buffer. The improved sensitization
      of fluorescence by the polymer observed in THF/buffer could be attributed to the
      weaker binding between the polymer and ssDNA-Fl and a decrease in dielectric
      constant of the solvent mixture, which disfavors electron transfer. THF-assisted
      signal sensitization was also observed for the polymer and fluorescein-labeled
      double-stranded DNA (dsDNA-Fl). These results indicate that the use of cosolvent
      provides a strategy to improve the detection sensitivity for biosensors based on
      the optical amplification provided by conjugated polymers.

PMID- 17441188
TI  - Variable-temperature powder X-ray diffraction of aromatic carboxylic acid and
      carboxamide cocrystals.
AB  - The effect of temperature on the cocrystallization of benzoic acid (BA),
      pentafluorobenzoic acid (FBA), benzamide (BAm), and pentafluorobenzamide (FBAm)
      is examined in the solid state. BA and FBA formed a 1:1 complex 1 at ambient
      temperature by grinding with a mortar and pestle. Grinding FBA and BAm together
      resulted in partial conversion into the 1:1 adduct 2 at 28 degrees C and complete
      transformation into the product cocrystal at 78 degrees C. Further heating (80
      100 degrees C) and then cooling to room temperature gave a different powder
      pattern from that of 2. BAm and FBAm hardly reacted at ambient temperature, but
      they afforded the 1:1 cocrystal 3 by melt cocrystallization at 110-115 degrees C.
      Both BA+FBAm (4) and BA+BAm (5) reacted to give new crystalline phases upon
      heating, but the structures of these products could not be determined owing to a
      lack of diffraction-quality single crystals. The stronger COOH and CONH2 hydrogen
      bonding groups of FBA and FBAm yielded the equimolar cocrystal 6 at room
      temperature, and heating of these solids to 90-100 degrees C gave a new
      crystalline phase. The X-ray crystal structures of 1, 2, 3, and 6 are sustained
      by the acid-acid/amide-amide homosynthons or acid-amide heterosynthon, with
      additional stabilization from phenyl-perfluorophenyl stacking in 1 and 3. The
      temperature required for complete transformation into the cocrystal was monitored
      by in situ variable-temperature powder X-ray diffraction (VT-PXRD), and formation
      of the cocrystal was confirmed by matching the experimental peak profile with the
      simulated diffraction pattern. The reactivity of H-bonding groups and the
      temperature for cocrystallization are in good agreement with the donor and
      acceptor strengths of the COOH and CONH2 groups. It was necessary to determine
      the exact temperature range for quantitative cocrystallization in each case
      because excessive heating caused undesirable phase transitions.

PMID- 17441189
TI  - Glass transitions of ordinary and heavy water within silica-gel nanopores.
AB  - The dynamic properties of water confined within nanospaces are of interest given
      that such water plays important roles in geological and biological systems. The
      enthalpy-relaxation properties of ordinary and heavy water confined within silica
      gel voids of 1.1, 6, 12, and 52 nm in average diameter were examined by adiabatic
      calorimetry. Most of the water was found to crystallize within the pores above
      about 2 nm in diameter but to remain in the liquid state down to 80 K within the
      pores less than about 1.6 nm in diameter. Only one glass transition was observed,
      at T(g) = 119, 124, and 132 K for ordinary water and T(g) = 125, 130, and 139 K
      for heavy water, in the 6-, 12-, and 52-nm diameter pores, respectively. On the
      other hand, two glass transitions were observed at T(g) = 115 and 160 K for
      ordinary water and T(g) = 118 and 165 K for heavy water in the 1.1-nm pores.
      Interfacial water molecules on the pore wall, which remain in the noncrystalline
      state in each case, were interpreted to be responsible for the glass transitions
      in the region 115-139 K, and internal water molecules, surrounded only by water
      molecules in the liquid state, are responsible for those at 160 or 165 K in the
      case of the 1.1-nm pores. It is suggested that the glass transition of bulk
      supercooled water takes place potentially at 160 K or above due to the
      development of an energetically more stable hydrogen-bonding network of water
      molecules at low temperatures.

PMID- 17441190
TI  - Development of a general and efficient iron-catalyzed epoxidation with hydrogen
      peroxide as oxidant.
AB  - The development of inexpensive and practical iron catalysts for the
      environmentally benign epoxidation of olefins with hydrogen peroxide as terminal
      oxidant is described. By systematic variation of ligands, metal sources, and
      reaction conditions, it was discovered that FeCl3 x 6 H2O in combination with
      pyridine-2,6-dicarboxylic acid and different amines shows high reactivity and
      excellent selectivity towards the epoxidation of aromatic olefins and moderate
      reactivity towards that of aliphatic olefins.

PMID- 17441191
TI  - Conformational polymorphism in N-(4'-methoxyphenyl)- 3-bromothiobenzamide.
AB  - Three conformational polymorphs of N-(4'-methoxyphenyl)-3-bromothiobenzamide,
      yellow alpha, orange beta, and yellow gamma, have been identified by single
      crystal X-ray diffraction. The properties and structure of the polymorphs were
      examined with FT Raman, FTIR (ATR), and UV/Vis spectroscopy, as well as
      differential scanning calorimetry. Computational data on rotational barriers in
      the isolated gas-phase molecule indicate that the molecular conformation found in
      the alpha form is energetically preferred, but only by around 2 kJ mol(-1) over
      the gamma conformation. The planar molecular structure found in the beta form is
      destabilized by 10-14 kJ mol(-1), depending on the calculation method. However,
      experimental evidence suggests that the beta polymorph is the most stable
      crystalline phase at room temperature. This is attributed to the relative
      planarity of this structure, which allows more and stronger intermolecular
      interactions, that is, more energetically effective packing. Calculated
      electronic-absorption maxima were in agreement with experimental spectra.

PMID- 17441192
TI  - Alkali-metal pyrazolate complexes with unusual pyrazolate coordination modes and
      pseudocubane motifs.
AB  - The dimeric complex [Li(Ph2pz)(OEt2)]2 (1) and tetrameric cluster
      [Na(Ph2pz)(thf)]4 (2) were prepared by treatment of alkali-metal reagents (nBuLi
      and Na{N(SiMe3)2}, respectively) with 3,5-diphenylpyrazole (Ph2pzH) in Et2O (1)
      or THF (2). The polymer [Na(tBu2pz)]n (3) was obtained from reaction at elevated
      temperature in a sealed tube between Na metal and 3,5-di-tert-butylpyrazole
      (tBu2pzH). The complex [Na4(tBu2pz)2(thf)3(obds)]2 (4; obds = (OSiMe2)2O) was
      obtained as a minor product from prolonged treatment of tBu2pzH with elemental
      sodium in a silicone-greased flask. All four alkali-metal pyrazolato complexes
      were characterized by IR and 1H NMR spectroscopy and X-ray crystallography.The Li
      dimer 1 displays mu-eta(2):eta(1) lithium-pyrazolato binding, in which both
      lithium atoms are four-coordinate. Room- and variable-temperature NMR studies
      (1H, 13C, and 7Li) of 1 suggest similar behavior in solution, with peaks
      coalescing at low temperatures. Complexes 2 and 4 display distorted cubane
      structures. In 2, all the sodium atoms are five-coordinate, whereas 4 contains
      two sodium/pyrazolate/thf clusters (4:2:3 ratio) bridged by two obds(2-) units,
      as well as two four-coordinate and two five-coordinate sodium atoms. Compound 3
      is composed of two independent chains with the unusual coordination modes mu3
      eta(5):eta(2):eta(2), mu3-eta(5):eta(2):eta(1), and mu3-eta(4):eta(2):eta(1),
      with five-, six-, and seven-coordinate sodium atoms. Two oxo-centered M8 cage
      complexes [(tBu2pz)6Li8O] (5) and [(tBu2pz)6Na8O] (6) were obtained as by
      products from attempted preparation of [Li(tBu2pz)] and [Na(tBu2pz)],
      respectively, and their structures were determined.

PMID- 17441194
TI  - Interpopulation variation in life-history traits of Poeciliopsis prolifica:
      implications for the study of placental evolution.
AB  - Placental reproduction is widespread across vertebrate taxa, but little is known
      about its life-history correlates and putative adaptive value. We studied
      variation in life-history traits in two populations of the placental poeciliid
      fish Poeciliopsis prolifica to determine whether differences in post
      fertilization maternal provisioning to embryos have a genetic basis and how food
      availability affects reproduction. Life histories were characterized for wild
      caught females and for second-generation lab-born females raised under two levels
      of food availability. We found that the two populations did not differ
      significantly in the wild for any life-history traits except for the lipid dry
      weight in females and in embryos at an advanced stage of development. When
      environmental effects were experimentally controlled, however, populations
      exhibited significant differences in several traits, including the degree of
      maternal provisioning to embryos. Food availability significantly affected female
      size at first parturition, brood size and offspring dry weight at birth.
      Altogether, these results demonstrate that population differences in maternal
      provisioning and other life-history traits have a genetic basis and show a
      plastic response to food availability. We infer that phenotypic plasticity may
      mask population differences in the field. In addition, when comparing life
      history patterns in these two populations with known patterns in placental and
      non-placental poeciliids, our results support the hypotheses that placentation is
      an adaptive reproductive strategy under high-resource conditions but that it may
      represent a cost under low-food conditions. Finally, our results highlight that
      age at maturity and reproductive allotment may be key life-history traits
      accompanying placental evolution.

PMID- 17441195
TI  - Structure of the cerebral cortex of the humpback whale, Megaptera novaeangliae
      (Cetacea, Mysticeti, Balaenopteridae).
AB  - Cetaceans diverged from terrestrial mammals between 50 and 60 million years ago
      and acquired, during their adaptation to a fully aquatic milieu, many derived
      features, including echolocation (in odontocetes), remarkable auditory and
      communicative abilities, as well as a complex social organization. Whereas brain
      structure has been documented in detail in some odontocetes, few reports exist on
      its organization in mysticetes. We studied the cerebral cortex of the humpback
      whale (Megaptera novaeangliae) in comparison to another balaenopterid, the fin
      whale, and representative odontocetes. We observed several differences between
      Megaptera and odontocetes, such as a highly clustered organization of layer II
      over the occipital and inferotemporal neocortex, whereas such pattern is
      restricted to the ventral insula in odontocetes. A striking observation in
      Megaptera was the presence in layer V of the anterior cingulate, anterior
      insular, and frontopolar cortices of large spindle cells, similar in morphology
      and distribution to those described in hominids, suggesting a case of parallel
      evolution. They were also observed in the fin whale and the largest odontocetes,
      but not in species with smaller brains or body size. The hippocampal formation,
      unremarkable in odontocetes, is further diminutive in Megaptera, contrasting with
      terrestrial mammals. As in odontocetes, clear cytoarchitectural patterns exist in
      the neocortex of Megaptera, making it possible to define many cortical domains.
      These observations demonstrate that Megaptera differs from Odontoceti in certain
      aspects of cortical cytoarchitecture and may provide a neuromorphologic basis for
      functional and behavioral differences between the suborders as well as a
      reflection of their divergent evolution.

PMID- 17441196
TI  - Novel reconstruction of the orientation of the pectoral girdle in sauropods.
AB  - The orientation of the scapulocoracoid in sauropod dinosaurs is reconstructed
      based on comparative anatomical investigations of pectoral girdles of extant
      amniotes. In the reconstruction proposed here, the scapula of sauropods stands at
      an angle of at least 55 degrees to the horizontal plane in mechanical coherence
      with the sternal apparatus including the coracoids. The coracoids are oriented
      cranioventrally to the rib cage and the glenoid is directed mediolaterally, which
      allows the humerus to swing in a sagittal plane. The inclination of the scapula
      to the horizontal plane is reconstructed for Diplodocus (60-65 degrees),
      Camarasaurus (60-65 degrees), and Opisthocoelicaudia (55-65 degrees). The
      inclination of the scapulocoracoid has consequences for the overall body posture
      in Camarasaurus and Opisthocoelicaudia, where the dorsal contour would have
      ventrally declined toward the sacrum. Scapulocoracoid mobility depends on the
      arrangement of clavicles, the reconstruction of a coracosternal joint, and the
      reconstructed musculature of the shoulder girdle. In a crocodylian model of the
      shoulder musculature, m. serratus profundus and superficialis form a muscular
      sling, which suspends the trunk from the shoulder girdle and would allow a
      certain mobility of the scapulocoracoid. An avian model of the shoulder
      musculature would also mean suspension by means of the m. serratus complex, but
      indicates a closer connection of the scapula to the dorsal ribs, which would lead
      to more restricted movements of the scapulocoracoid in sauropods.

PMID- 17441197
TI  - Regional multilineage differentiation potential of meniscal fibrochondrocytes:
      implications for meniscus repair.
AB  - The knee menisci are wedge-shaped semilunar fibrocartilaginous structures that
      reside between the femur and tibia and function to transmit and distribute load.
      These structures have characteristics of both fibrous and cartilaginous tissues.
      The cartilage-like inner region and the fibrous vascularized outer region each
      has a distinct extracellular matrix, and resident meniscal fibrochondrocytes
      (MFCs) with distinct morphologies dependent on their location. Damage to the
      meniscus is common, and disruption of tissue structure and function result in
      erosion of the underlying articular cartilage. It has been observed that damage
      in the vascular periphery undergoes spontaneous repair, whereas damage of the
      inner region does not heal. While vascularity of the peripheral region plays a
      role in healing, recent findings have also suggested that local cellular
      composition influences local healing capacity. This study examined the variation
      in multipotential characteristics of cell populations isolated from different
      regions of the bovine meniscus. MFCs were isolated from the outer (vascular),
      inner (avascular), and horn (mixed) regions and induced toward chondrogenic,
      adipogenic, and osteogenic lineages. The results of this study suggest that MFCs
      from all regions of the meniscus possess a multilineage differentiation
      capability, particularly toward chondrogenesis and adipogenesis. MFCs from the
      outer region were most plastic, differentiating along all three mesenchymal
      lineages. These findings may underlie the experimental observation of improved
      integration of meniscus grafts from the outer zone and may have implications for
      developing strategies of cell-based meniscus repair.

PMID- 17441198
TI  - Ovarian morphometrics in TP53-deficient mice.
AB  - The objective of these investigations was to characterize ovarian responses to
      hormonal stimulation in TP53-deficient mice. TP53-deficient (KO) and wild-type
      (WT) mice were induced to ovulate with pregnant mare serum gonadotropin followed
      by human chorionic gonadotropin. Effect of estradiol on ovarian morphology was
      determined in induced and control mice implanted with estradiol-containing or
      placebo pellets. Blood was collected and mice were killed 7 days following
      implantation. Preserved ovaries were serially sectioned and stained. Numbers of
      follicles (all classifications) decreased with ovulation induction, but did not
      differ between WT and KO mice. Numbers of corpora lutea (CL) were less in
      ovulation-induced KO mice treated with estradiol compared to WT mice. Area of
      individual CL and serum concentrations of progesterone were greater in ovulation
      induced KO mice given estradiol compared to WT mice. Ovulation-induced KO mice
      had more, larger hemorrhagic follicles than similarly treated WT mice, but
      hemorrhagic follicles were not influenced by estradiol. Proliferation of ovarian
      surface epithelial cells did not differ between KO and WT mice induced to ovulate
      and given estradiol. Ovaries from TP53 gene knockout mice (n = 4) induced to
      ovulate and given a 21-day estradiol implant three times over 58 days were
      observed for precursor lesions. There was no indication of precursor lesions in
      any TP53 KO or WT mouse. TP53 status did not influence recruitment of follicles,
      but TP53 deficiency hindered the ability of human chorionic gonadotropin to cause
      ovulation.

PMID- 17441199
TI  - Rapid inactivation and apoptosis of osteoclasts in the maternal skeleton during
      the bone remodeling reversal at the end of lactation.
AB  - There is a rapid reversal in maternal skeletal metabolism and bone remodeling
      from accelerated bone resorption during lactation to skeletal rebuilding after
      lactation. The purpose was to determine the changes that occur in maternal
      osteoclasts during the transition from lactation to postlactation. Skeletal
      samples were taken from female rats on days 10 and 19 of lactation and 1 and 7
      days after lactation. The pups were weaned on day 20. There was a rapid change in
      the osteoclast population after weaning, resulting in less resorption surface.
      Osteoclasts detached from bone surfaces, lost their ruffled borders, and became
      fragmented with immunocytochemical evidence of apoptosis within 24 hr after
      lactation. Concomitant with the rapid regression in the osteoclast population was
      an over fivefold increase in maternal calcitonin (CT) levels at 24 hr after
      weaning. Serum calcium and estrogen (E2) increased, but prolactin (PRL) and PTH
      decreased after weaning. The hormone changes, particularly that of CT, are
      consistent with the rapid regression of the osteoclast population at the end of
      lactation. These changes are similar to a reversal phase of a bone remodeling
      cycle where bone formation commences when resorption ceases on bone surfaces and
      suggests that the fate of osteoclasts during bone remodeling is programmed cell
      death. These results also suggest that bone remodeling is well synchronized prior
      to, during, and after lactation to accommodate the mineral requirements of the
      offspring as well as the mother.

PMID- 17441200
TI  - Osteoclast distribution within the rat interdental septum coincident to
      experimental tooth movement using light forces.
AB  - There is little quantitative information concerning the number and distribution
      of bone-matrix resorbing osteoclasts (BMRO) within the adjacent alveolar bone
      coincident to tooth movement. We moved the right first maxillary molar tooth
      anteriorly in 40 female rats (E), the left side was untreated, serving as an
      internal control (IC). Forty female age and weight matched rats were untreated,
      serving as external controls (EC). BMRO were identified on periosteal and
      endosteal surfaces of the interdental septum from 1-5 days after initial force
      application using the MTB-322 antibody. The number of BMRO at periosteal surfaces
      of E was greater in IC and EC from 2-5 days (P < 0.001). Similarly, the number of
      BMRO at endosteal surfaces was greater from 1-5 days (P < 0.001). The number of
      BMRO at periosteal and endosteal surfaces was greater within E than within EC
      from 1-5 days (P < 0.001). Outcome data from IC were often significantly
      different from EC. Our data suggest that relatively low forces increase the
      number of BMRO, which are not uniformly distributed onto both periosteal and
      endosteal surfaces. Thus, the interdental septum resorbs at the alveolar wall and
      within spaces between the trabeculae, which, taken together, results in net
      removal of bone from areas of compression. These data also suggest that
      experimental tooth movement produces significant differences in the number and
      distribution of BMRO within IC and EC. Thus, EC groups should be included in
      studies of tooth movement.

PMID- 17441201
TI  - Total neocortical cell number in the mysticete brain.
AB  - The cetacean brain has long been of scientific interest, not only because of its
      large size - the largest in the animal kingdom - but also because of its high
      gyrification. It shows several adaptations to the aquatic environment, especially
      in the cortical arrangements of functional areas. To study structural aspects of
      the mysticete brain we estimated neocortical features in the common minke whale
      using stereological methods. The neocortex was surprisingly thick, equal to that
      in humans. The total neocortical neuron number was 12.8 x 10(9), and the total
      neocortical glia number 98.2 x 10(9). Total cell numbers in the auditory and
      visual cortex were also estimated, and showed that the auditory cortex contained
      more cells than the visual cortex. In this small sample, no sexual dimorphism was
      seen within the neocortex of the common minke whale. Our aim was to estimate the
      total cell number, cortical volume and cell density in the entire mysticete
      neocortex and compare the total cell number in the auditory cortex with that of
      the visual cortex using stereological methods. Here, we used the common minke
      whale as a model of all mysticetes. We wanted to compare these neocortical
      features to those of other mammals to forward understanding of the evolution of
      the mammalian brain.

PMID- 17441202
TI  - Postnatal development of noradrenergic terminals in the rat trigeminal motor
      nucleus: A light and electron microscopic immunocytochemical analysis.
AB  - The noradrenergic (NA) innervation in the trigeminal motor nucleus (Vmot) of
      postnatal and adult rats was examined by light and electron microscopic
      immunocytochemistry using antibodies against dopamine-beta-hydroxylase or
      tyrosine hydroxylase. NA fibers were identified in the Vmot as early as the day
      of birth (postnatal day 0; P0). A continuous increase in the density of labeled
      fibers was observed during development up to P20, with a slight decrease at P30
      and in the adult. Electron microscopic analysis of serial ultrathin sections
      revealed that, at P5, nearly half (46%) of the examined NA terminals made
      synaptic contact with other neuronal elements with membrane specializations. The
      percentage of examined NA varicosities engaged in synaptic contacts increased at
      P15 (74%), then decreased in the adult (64%). At all developmental ages, the
      majority of contacts made by these boutons were symmetrical, the postsynaptic
      elements being mainly dendrites and occasionally somata. Interestingly, some of
      the NA terminals made axo-axon contacts with other unidentified boutons. These
      results show that, although the density of NA fibers increases during postnatal
      development, functional NA boutons are present in the Vmot at early postnatal
      ages. Some of these fibers might exert their effects via nonsynaptic release of
      noradrenaline, the so-called volume transmission, but, in the main, they form
      conventional synaptic contacts with dendrites, somata, and other axonal terminals
      in the Vmot. These results are consistent with previous electrophysiological
      studies that propose an important role for the NA system in modulating
      mastication.

PMID- 17441203
TI  - How regenerating lymphatics function: lessons from lizard tails.
AB  - Rational treatment of lymphoedema may be improved in the future with a better
      understanding of the physiological processes involved in the regeneration of new
      lymphatic vessels (lymphangiogenesis). Many lizard species undergo tail autotomy
      as a predator escape response and subsequently regenerate nonlymphoedematous
      tails. Such species may offer novel models for examining lymphangiogenesis. In
      this lymphoscintigraphic evaluation, three radioactive tracers were employed,
      (99m)Tc-antimony trisulphide colloid (approximately 10 nm diameter), (99m)Tc-tin
      fluoride colloid (approximately 2,000 nm; (99m)Tc-TFC), and (99m)Tc
      diethylenetriaminepentaacetic acid (soluble; (99m)Tc-DTPA), to examine lymphatic
      function in regenerating tails of the Australian marbled gecko, Christinus
      marmoratus. Rate of local clearance and velocity of migration were determined in
      geckos with original tails and at 6, 9, 12, and >24 weeks after autotomy. In
      original-tailed geckos, the smaller radiocolloid was cleared to a greater extent
      and had a faster lymph velocity than in geckos with regenerated tails. The same
      parameters measured for larger particles were greater in early regeneration than
      later. (99m)Tc-TFC did not migrate from the injection site in fully regenerated
      and original gecko tails, which indicates that larger particles are increasingly
      impeded as tail regeneration progresses. Soluble (99m)Tc-DTPA diffused from the
      injection site extremely rapidly via venous capillaries in all tails, confirming
      that the slower clearance of the colloids is solely via the lymphatics.
      Differences in clearance and lymph velocity between differently sized colloids
      throughout tail regeneration may be influenced by changes in surrounding tissue
      structure density and the lymphatic vessel porosity.

PMID- 17441204
TI  - Nkx2.5-negative myocardium of the posterior heart field and its correlation with
      podoplanin expression in cells from the developing cardiac pacemaking and
      conduction system.
AB  - Recent advances in the study of cardiac development have shown the relevance of
      addition of myocardium to the primary myocardial heart tube. In wild-type mouse
      embryos (E9.5-15.5), we have studied the myocardium at the venous pole of the
      heart using immunohistochemistry and 3D reconstructions of expression patterns of
      MLC-2a, Nkx2.5, and podoplanin, a novel coelomic and myocardial marker.
      Podoplanin-positive coelomic epithelium was continuous with adjacent podoplanin-
      and MLC-2a-positive myocardium that formed a conspicuous band along the left
      cardinal vein extending through the base of the atrial septum to the posterior
      myocardium of the atrioventricular canal, the atrioventricular nodal region, and
      the His-Purkinje system. Later on, podoplanin expression was also found in the
      myocardium surrounding the pulmonary vein. On the right side, podoplanin-positive
      cells were seen along the right cardinal vein, which during development persisted
      in the sinoatrial node and part of the venous valves. In the MLC-2a- and
      podoplanin-positive myocardium, Nkx2.5 expression was absent in the sinoatrial
      node and the wall of the cardinal veins. There was a mosaic positivity in the
      wall of the common pulmonary vein and the atrioventricular conduction system as
      opposed to the overall Nkx2.5 expression seen in the chamber myocardium. We
      conclude that we have found podoplanin as a marker that links a novel Nkx2.5
      negative sinus venosus myocardial area, which we refer to as the posterior heart
      field, with the cardiac conduction system.

PMID- 17441205
TI  - Comparative morphometrics of embryonic facial morphogenesis: implications for
      cleft-lip etiology.
AB  - Cleft lip (CL) with or without cleft palate (CL[P]) has a complex etiology but is
      thought to be due to either genetic or environmentally induced disruptions of
      developmental processes affecting the shape and size of the facial prominences
      (medial nasal, lateral nasal, and maxilla). Recent advances in landmark-based
      morphometrics enable a rigorous reanalysis of phenotypic shape variation
      associated with facial clefting. Here we use geometric morphometric (GM) tools to
      characterize embryonic shape variation in the midface and head of six strains of
      mice that are both cleft-liable (A, A/WySn, CL/Fr) and normal (BALB/cBy, C57BL,
      CD1). Data were comprised of two-dimensional landmarks taken from frontal and
      lateral photographs of embryos spanning the time period in which the facial
      prominences fuse (GD10-12). Results indicate that A/- strain mice, and
      particularly A/WySn, have overall smaller midfaces compared to other strains. The
      A/WySn strain also has significant differences in facial shape related to
      retarded development. Overall, CL/Fr strain mice are normal-sized, but tend to
      have undersized maxillary prominences that do not project anteriorly and have a
      small nasal contact area. These results suggest that the etiology of clefting
      differs in A/WySn and CL/Fr strains, with the former strain suffering disruptions
      to developmental processes affecting overall size (e.g., neural crest migration
      deficiencies and lower mitotic activity), while the latter strain has defects
      restricted to the shape and size of the maxilla. A combination of molecular
      experimentation and phenotypic analysis of shape is required to test these
      hypotheses further.

PMID- 17441206
TI  - An exciting centennial year for The Anatomical Record.

PMID- 17441207
TI  - Striated muscle and nerve fascicle distribution in the female rat urethral
      sphincter.
AB  - The anatomical basis for urinary continence depends on a thorough understanding
      of the tissues in the urethra. The objective of this study was to evaluate the
      morphology and neuroanatomy of urethral striated muscle, called the
      rhabdosphincter or external urethral sphincter, in normal female rats. Urethras
      from 12 female rats were dissected from the bladder, fixed, embedded in paraffin
      or epon, and sectioned every 1 mm. Striated muscle content was taken as the ratio
      of the striated muscle area to net urethral area. Nerve fascicles containing
      myelinated axons near the rhabdosphincter were counted and mapped. Both striated
      muscle content and number of nerve fascicles peak in the proximal third of the
      urethra, with a secondary peak at the distal end of the urethra. This secondary
      peak may correspond to an analog of the combined compressor
      urethrae/urethrovaginal sphincter located in the distal urethra in human. The
      rhabdosphincter has a variable distribution along the length of the urethra. In
      the middle and distal thirds of the urethra, the dorsal striated muscle fibers
      between the urethra and vagina become more sparse. The majority of nerve
      fascicles are contained in the lateral quadrants of the urethra, similar to the
      lateral distribution of somatic nerves in humans. In conclusion, this study
      demonstrates the normal distribution of the striated musculature and neuroanatomy
      in the urethra, with similarities to the human. It thus supports and extends the
      usefulness of the rat as an experimental model for studying urinary incontinence.

PMID- 17441209
TI  - Early morphogenesis of the sinuatrial region of the chick heart: a contribution
      to the understanding of the pathogenesis of direct pulmonary venous connections
      to the right atrium and atrial septal defects in hearts with right isomerism of
      the atrial appendages.
AB  - The morphogenesis of the sinuatrial region of embryonic hearts is still not well
      understood. Current matters of dispute are the topogenesis of the future
      pulmonary vein orifice and the topogenesis of the primary atrial septum. We
      analyzed the development of the sinuatrial region in chick embryos ranging from
      Hamburger and Hamilton (HH) stage 14 to 25. Our study disclosed three features of
      sinuatrial development. First, the primitive atrium of the HH stage 16 chick
      embryo heart has a separate inflow component. This inflow component takes up the
      mouth of the confluence of the systemic veins (sinus venosus) as well as the
      future mouth of the common pulmonary vein (pulmonary pit). The left portion of
      the atrial inflow component becomes incorporated into the left atrium and its
      right portion becomes incorporated into the right atrium. Rightward growth of the
      sinuatrial fold separates the sinus venosus from the left atrium. Second, the
      pulmonary pit originally forms as a bilaterally paired structure. Its left and
      right portions are connected to the left and right portions of the atrial inflow
      component, respectively. Normally, only the left portion of the pulmonary pit
      deepens to form the common pulmonary vein orifice, whereas the right portion
      disappears. Third, the primary atrial septum of the chick heart is not formed at
      the original midline of the embryonic heart, but is formed to the left of the
      original midline. This finding is in accord with molecular data suggesting that
      the primary atrial septum derives from the left heart-forming field. Our findings
      shed new light on the pathogenesis of direct pulmonary venous connections to the
      right atrium and atrial septal defects in hearts with right isomerism of the
      atrial appendages.

PMID- 17441208
TI  - Parathyroid hormone/parathyroid hormone-related peptide modulates growth of avian
      sternal cartilage via chondrocytic proliferation.
AB  - Parathyroid hormone (PTH; 10(-7) to 10(-15) M) decreased terminal chondrogenesis
      in the avian sterna. During the first half of an 8-day culture, 100 nM PTH (1-34)
      significantly increased sternal length and downregulated the deposition of type X
      collagen and its mRNA expression. However, it remains unclear how PTH increased
      cartilaginous growth. In this study, we examined growth by both cell
      proliferation and analysis of cyclin d1 and collagen mRNA. Types II, IX, and X
      collagens and cyclin d1 mRNA were quantified through real-time RT-PCR, while Ki
      67 was used as an immunohistochemical proliferation marker. Extracellular matrix
      content was measured through mRNA quantification of types II, IX, and X collagen
      and observing deposition of the same collagens. PTH significantly increased the
      proliferation marker Ki-67 in the sternal cephalic region. There was less type II
      and X collagen in PTH-treated sterna with concomitant decreases in mRNA
      production, suggesting that proliferation was the major contributor to cartilage
      growth in the presence of PTH/PTH-related peptide receptor activation. In
      conclusion, these experiments demonstrated that PTH increased cartilage growth by
      upregulating cell proliferation or other extracellular matrix components.

PMID- 17441210
TI  - Nerve terminal contributes to acetylcholine receptor organization at the
      dystrophic neuromuscular junction of mdx mice.
AB  - Changes in the distribution of acetylcholine receptors have been reported to
      occur at the neuromuscular junction of mdx mice and may be a consequence of
      muscle fiber regeneration rather than the absence of dystrophin. In the present
      study, we examined whether the nerve terminal determines the fate of
      acetylcholine receptor distribution in the dystrophic muscle fibers of mdx mice.
      The left sternomastoid muscle of young (1-month-old) and adult (6-month-old) mdx
      mice was injected with 60 microl lidocaine hydrochloride to induce muscle
      degeneration-regeneration. Some mice had their sternomastoid muscle denervated at
      the time of lidocaine injection. After 10 days of muscle denervation, nerve
      terminals and acetylcholine receptors were labeled with 4-Di-2-ASP and rhodamine
      alpha-bungarotoxin, respectively, for confocal microscopy. In young mdx mice, 75%
      (n = 137 endplates) of the receptors were distributed in islands. The same was
      observed in 100% (n = 114 endplates) of the adult junctions. In denervated
      regenerated fibers of young mice, the receptors were distributed as branches in
      89% of the endplates (n = 90). In denervated-regenerated fibers of adult mice,
      the receptors were distributed in islands in 100% of the endplates (n = 100).
      These findings show that nerve-dependent mechanisms are also involved in the
      changes in receptor distribution in young dystrophic muscles. In older dystrophic
      muscles, other factors may play a role in receptor distribution.

PMID- 17441211
TI  - Ultrastructural comparison of the morphology of three different platelet and
      fibrin fiber preparations.
AB  - The aim of the current study was to investigate the ultrastructural morphology of
      three different sources of fibrin networks and platelets, namely, lyophilized
      human platelet-rich plasma (LPRP), freshly prepared human platelet-rich plasma
      (FPRP), and human platelet concentrate (HPC). The ultrastructural morphology of
      the three different fibrin networks was studied using the scanning electron
      microscope (SEM). Turbidity curves were drawn at 405 nm at room temperature and
      fibrinogen concentrations were measured. Scanning electron micrographs showed
      that all clots produced thick major fibrin fibers as well as a well-defined fine
      fibrin network, which appeared to be a superimposed process that occurred after
      the major fibrin network was established. These features were decidedly more
      pronounced in the HPC specimens. Turbidity curves of the three types of plasma
      showed differences in LPRP and FPRP. Fibrinogen concentrations of all three
      preparations were in the normal ranges. Because of the great similarity between
      LPRP, HPC, and FPRP, we suggest that LPRP could be used successfully to study
      morphological changes in fibrin fibers and platelets, which may occur after
      exposure to certain therapeutic agents. However, functionality studies such as
      turbidity curves should concurrently be included. We therefore conclude that from
      a basic science point of view, LPRP is a valuable research tool and that such
      results may add information that could be valuable for clinical application.

PMID- 17441212
TI  - Desmosomes are unaltered during infections by attaching and effacing pathogens.
AB  - The human attaching and effacing (A/E) intestinal pathogens enterohemorrhagic
      Escherichia coli (EHEC), enteropathogenic E. coli (EPEC), and the murine A/E
      pathogen Citrobacter rodentium cause serious diarrhea in their hosts. These
      bacteria alter numerous host cell components, including organelles, the host cell
      cytoskeleton, and tight junctions during the infectious process. One of the
      proteins that contribute to the intermediate filament network in host cells,
      cytokeratin-18, is extensively altered during EPEC infections. Based on this, we
      tested the hypothesis that desmosomes, the only intercellular junctions that
      interact with intermediate filaments, are also influenced by A/E pathogen
      infections. We found that the desmosomal transmembrane proteins desmoglein and
      desmocollin, as well as the desmosome plaque protein desmoplakin, all remain
      unchanged during EPEC infection in vitro. This evidence is corroborated by the
      unaltered localization of desmoglein and desmoplakin in vivo in mice infected
      with C. rodentium for 7 days. Electron microscopic analysis of 7-day C. rodentium
      infected murine colonocytes also show no observable differences in the desmosomes
      when compared to uninfected controls. Our data suggest that, unlike tight
      junctions, the desmosome protein levels and localization, as well as desmosome
      morphology, are unaltered during A/E pathogenesis.

PMID- 17441213
TI  - Apoptosis and blood-testis barrier during the first spermatogenic wave in the
      pubertal rat.
AB  - This research explores the initial assembly of the blood-testis barrier (BTB)
      during puberty, when a massive physiological apoptosis in the first spermatogenic
      wave takes place. Fragments of testis from 14- to 20-day-old rats were studied by
      conventional transmission electron microscopic techniques. Lanthanum hydroxide
      was used as an intercellular tracer. Light microscopy was used to confirm
      apoptotic death when paraffin-embedded sections were studied by TUNEL analysis.
      When the seminiferous cords reached the zygotene-pachytene spermatocyte level,
      they exhibited abundant apoptotic figures, whereas the remaining segments showed
      sporadic apoptosis. We found a BTB not yet assembled in the cords with zygotene
      pachytene spermatocytes and abundant apoptosis. The observed apoptosis frequency
      diminished drastically when BTB was organized, as confirmed by the use of the
      tracer. Our conclusion is that the massive apoptosis found in the zygotene
      pachytene spermatocytes between days 14 and 20 coincides with an open BTB. The
      absence of BTB could be one of the factors causing massive apoptosis of zygotene
      pachytene spermatocytes, at least within the time span analyzed. The zygotene
      pachytene spermatocytes are left exposed in an open environment instead of being
      isolated in the adluminal compartment to which they are destined.

PMID- 17441214
TI  - Effects of red grape skin and seed extract supplementation on atherosclerosis in
      Watanabe heritable hyperlipidemic rabbits.
AB  - Epidemiological studies have suggested an association between consumption of red
      wine and other polyphenolic compounds and prevention of cardiovascular diseases.
      In the present study, Watanabe heritable hyperlipidemic (WHHL) rabbits were used
      to investigate the effects of polyphenols in a red grape skin and seed extract
      (GSE) on the development of atherosclerosis. WHHL rabbits received either
      semisynthetic diet (casein based) or semisynthetic diet added GSE over a period
      of 15 wk. Plasma lipids and aortic cholesterol accumulation were measured.
      Feeding semisynthetic diet was associated with increasing hypercholesterolemia,
      which was developing slower in GSE group compared to the controls as recorded by
      significantly lower plasma cholesterol in dosage week 7 (males: P < 0.05,
      females: P < 0.01) and 11 (males: P < 0.01). Aortic atherosclerosis evaluated as
      the cholesterol content in aortic tissue was comparable in the control and GSE
      dosed females, but it was significantly reduced in the abdominal part of GSE
      dosed male compared to the controls (P < 0.05). In conclusion, feeding GSE
      extract to WHHL rabbits had no significant effects in females but was associated
      with transient less hypercholesterolemic response to semisynthetic diet and,
      furthermore, retarded the development of aortic atherosclerosis in males as
      demonstrated by significantly lower cholesterol content in the abdominal part.

PMID- 17441215
TI  - Therapeutic targets in chronic myeloid leukaemia.
AB  - Chronic myeloid leukaemia (CML) is a clonal disorder of the haemopoietic stem
      cell arising as a consequence of the formation of the bcr-abl oncogene. The
      particular molecular basis of this condition has enabled the development of
      therapies that selectively target diseased cells. The success of the rationally
      designed first-line therapy imatinib mesylate (IM) is tempered by the problems of
      disease persistence and resistance. Novel strategies have been identified to take
      forward therapy in CML and these will be discussed in this review. This work is
      generated from a review of published literature and contains particular insight
      into the work performed by our group in this field.

PMID- 17441216
TI  - Simultaneous determination of hydroxysafflor yellow A and ferulic acid in rat
      plasma after oral administration of the co-extractum of Rhizoma chuanxiong and
      Flos Carthami by HPLC-diode array detector.
AB  - A simple, rapid and accurate HPLC method has been developed for simultaneous
      determination of hydroxysafflor yellow A and ferulic acid in rat plasma after
      oral administration of the co-extractum of Rhizoma chuanxiong and Flos Carthami.
      Plasma samples were deproteinized with 6% perchloric acid, and riboflavin was
      used as internal standard. The supernatant after centrifuge was injected into a
      Shimadzu C(18) (150 x 4.6 mm, i.d. 5 microm) column. Gradient elution for A:B (0
      min, 90:10; 25 min, 70:30; 27 min, stop) was applied. The mobile phase was
      composed of 0.022 mol/L potassium dihydrogen phosphate solutions, adjusted to pH
      3.0 with phosphoric acid for pump A, and 90% (v/v) acetonitrile for pump B. The
      assay was shown to be linear over the range 0.046-4.6 microg/mL (r(2) = 0.9995)
      for hydroxysafflor yellow A and 0.037-3.7 microg/mL (r(2) = 0.9998) for ferulic
      acid. Mean recovery was 97.5% for hydroxysafflor yellow A and 83.6% for ferulic
      acid. Both of the intra-day and inter-day precisions were <or=8.1%. The limits of
      quantification of hydroxysafflor yellow A and ferulic acid were 0.046 and 0.037
      microg/mL, respectively. The HPLC method was successfully applied to the
      pharmacokinetic studies of hydroxysafflor yellow A and ferulic acid in rat plasma
      after oral administration of the co-extractum of Rhizoma chuanxiong and Flos
      Carthami.

PMID- 17441217
TI  - Stable isotope dilution analysis of N-acetylaspartic acid in urine by liquid
      chromatography electrospray ionization tandem mass spectrometry.
AB  - N-acetylaspartic acid (NAA) is a specific urinary marker for Canavan disease, an
      autosomal recessive leukodystrophy. We developed a 'dilute and shoot' stable
      isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) method
      for determination of NAA in urine. Deuterated internal standard d(3)-NAA was
      added to untreated urine and the mixture was injected into the LC-MS/MS system
      operated in the negative ion mode. Chromatography was carried out on a C(8)
      minibore column using 50% acetonitrile solution containing 0.05% formic acid at a
      flow rate of 0.25 mL/min. The retention time was 1.6 min and the turnaround time
      was 2.2 min. NAA and d(3)-NAA were analyzed in multiple reaction monitoring mode.
      Calibrators and quality control samples were prepared in pooled control urine.
      The assay was linear up to 2000 micromol/L with limit of quantification at 1
      micromol/L (S/N = 12). Interassay and intraassay coefficients of variation were
      less than 7% and recovery at three different concentrations was 98.9-102.5%. The
      LC-MS/MS method for NAA as described involves no extraction and no
      derivatization, showed no interference and gave excellent recovery with low
      variability and short analytical time. The method was successfully applied for
      the retrospective analysis of urine from 21 Canavan disease cases.

PMID- 17441218
TI  - Resolution of oligosaccharides in glycopeptides using immobilized Endo-M and
      ultra-performance liquid chromatography with electrospray ionization time-of
      flight mass spectrometry.
AB  - The resolution of asparagine-linked oligosaccharides in glycopeptides was carried
      out by combination of the transglycosylation reaction and ultra-performance
      liquid chromatography with electrospray ionization time-of-flight mass
      spectrometry (UPLC-ESI-TOF-MS). The resolution of the oligosaccharides is based
      on the enzymic transglycosylation reaction with Endo-beta-N-acetylglucosaminidase
      (Endo-M) isolated from Mucor hiemalis. The oligosaccharides were transferred to a
      fluorescent acceptor (NDA-Asn-GlcNAc) with Endo-M to produce the fluorescent
      oligosaccharides. In the present research, the enzyme was also immobilized in the
      well of a microassay plate by the sol-gel technique. The transglycosylation
      reaction was easily managed due to the immobilization. Furthermore, multiple use
      was possible by the encapsulated Endo-M. The resulting fluorescent
      oligosaccharides were separated by UPLC and efficiently detected by ESI-TOF-MS.
      Several oligosaccharides in ovalbumin were successfully identified by the
      proposed procedure.

PMID- 17441219
TI  - Simultaneous determination of midazolam and 1'-hydroxymidazolam in human plasma
      by liquid chromatography with tandem mass spectrometry.
AB  - A sensitive and simple liquid chromatography-tandem mass spectrometry method for
      the determination of midazolam and 1'-hydroxymidazolam in human plasma has been
      developed and validated with a dynamic range of 0.1-250 ng/mL. The analysis was
      based on semi-automated liquid-liquid extraction followed by evaporation of the
      extraction solvent, reconstitution and chromatography on a reversed-phase C(18)
      column. The mobile phase consists of 5 mm ammonium acetate and methanol and runs
      in gradient at a flow rate of 0.25 mL/min with column temperature of
      approximately 20 degrees C. The entire column effluent was transferred into the
      LC-MS/MS interface operated in positive electrospray ionization mode. The
      chromatographic run time was 4.3 min per injection, with retention times for
      midazolam, 1'-hydroxymidazolaml and the internal standard, triazolam, of 2.5, 2.3
      and 2.1 min, respectively. The intra-day and inter-day precision (RSD %) and
      accuracy (bias %) of the quality control samples were <15.0% and within +/-13%,
      respectively. The current method has been applied to a clinical drug-drug
      interaction study in human.

PMID- 17441220
TI  - Glow discharge electron impact ionization source for miniature mass
      spectrometers.
AB  - A glow discharge electron impact ionization (GDEI) source was developed for
      operation using air as the support gas. An alternative to the use of
      thermoemission from a resistively heated filament electron source for miniature
      mass spectrometers, the GDEI source is shown to have advantages of long lifetime
      under high-pressure operation and low power consumption. The GDEI source was
      characterized using our laboratory's handheld mass spectrometer, the Mini 10. The
      effects of the discharge voltage and pressure were investigated. Design
      considerations are illustrated with calculations. Performance is demonstrated in
      a set of experimental tests. The results show that the low power requirements,
      mechanical ruggedness, and quality of the data produced using the small glow
      discharge ion source make it well-suited for use with a portable handheld mass
      spectrometer.

PMID- 17441221
TI  - Quantitative determination of dihydrostreptomycin in bovine tissues and milk by
      liquid chromatography-electrospray ionization-tandem mass spectrometry.
AB  - Dihydrostreptomycin (DHS) is an aminoglycoside antibiotic used in veterinary
      medicine in combination with benzylpenicillin for the treatment of bacterial
      infections in cattle, pigs and sheep. A method to determine its residues in
      edible tissues of cattle, as well as in milk, was developed and validated.
      Extraction of DHS from the tissues was performed using a liquid extraction with a
      10 mM phosphate buffer containing 2% (w/v) trichloroacetic acid, while milk
      samples were treated with a 50% (w/v) trichloroacetic acid solution, followed by
      a solid-phase clean-up procedure on a carboxypropyl (CBA) weak cation exchange
      column. Ion-pair chromatography, using a mixture of 20 mM pentafluoropropionic
      acid in water and acetonitrile as the mobile phase, was used to retain DHS and
      the internal standard streptomycin (STR) on a Nucleosil (5 microm) reversed-phase
      C18 column. The components were detected and quantified by electrospray
      ionization (ESI) tandem mass spectrometry. The method could be validated
      according to EC (European Community) requirements with respect to linearity,
      trueness and precision, the latter evaluated at the maximum residue limit (MRL) -
      1000 ng g(-1) for kidney, 500 ng g(-1) for muscle, liver and fat, and 200 ng g(
      1) for milk -, at one-half of the MRL and at one and a half times the MRL. A
      limit of quantification of 10 ng g(-1) and 1 ng ml(-1) was obtained for all
      tissues and for milk, respectively, which is far below one-half of the MRL as
      requested, while the limit of detection was in the low ppb range, varying between
      1.9 and 4.2 ng g(-1) for the different tissues tested, and being 0.6 ng ml(-1)
      for milk. The method was used for the monitoring of DHS residues in incurred
      tissue and milk samples coming from cattle medicated with DHS in combination with
      benzylpenicillin by intramuscular injection, in order to evaluate withdrawal
      times.

PMID- 17441222
TI  - Prenatal diagnosis of Smith-Lemli-Opitz syndrome (SLOS) by DHCR7 mutation
      analysis.
AB  - OBJECTIVES: We review our experience using mutation analysis of the DHCR7 gene
      for prenatal diagnosis of Smith-Lemli-Opitz syndrome (SLOS), an autosomal
      recessive disorder of endogenous cholesterol biosynthesis caused by deficiency of
      7-dehydrocholesterol reductase (DHCR7). METHODS AND RESULTS: Prenatal diagnosis
      of SLOS was conducted for 21 pregnancies involving 15 families. DNA was isolated
      directly from amniotic fluid cells or chorionic villus samples (CVS), and the
      DHCR7 gene was screened for the parental mutations using PCR-ARMS and nucleotide
      sequencing. Sixteen of the pregnancies were unaffected and five were affected.
      There have been no incidences of misdiagnosed pregnancies. CONCLUSIONS: DHCR7
      mutation is a rapid and reliable method for prenatal diagnosis of SLOS, and
      provides an alternative to specialized biochemical tests for elevated 7DHC in
      amniotic fluid or CVS.

PMID- 17441223
TI  - Flow cytometric assessment of feto-maternal hemorrhage; a comparison with Betke
      Kleihauer.
AB  - OBJECTIVES: Assessing the number of fetal cells in the maternal circulation
      quantifies the volume of feto-maternal hemorrhage, enhancing the ability to
      provide effective prevention of Rhesus (Rh) allommunization and appropriate fetal
      surveillance in cases of significant feto-maternal hemorrhage. METHODS: Having
      developed a standard curve with maternal samples spiked with known volumes of
      fetal red blood cells, we used a flow cytometric method using fluorescent labeled
      antihemoglobin F to quantitate fetal cells in the maternal circulatory system in
      two groups of women undergoing chorionic villus sampling (CVS), by either biopsy
      forceps or cannula aspiration (n = 170 women). We compared these results with the
      gold standard, the Betke-Kleihauer test. RESULTS: Our results show good
      correlation between the flow cytometric method and the traditional Betke
      Kleihauer method for fetal red cell quantitation (r(2) = 0.99). Fetal red blood
      cells were identified in 10 women by the Betke-Kleihauer method, and in 26 women
      by flow cytometry. CVS was not associated with an increase in feto-maternal
      hemorrhage. CONCLUSION: Flow cytometry was both more sensitive and more timely
      for the quantitation of feto-maternal hemorrhage than was Betke-Kleihauer.

PMID- 17441225
TI  - Notice of retraction: "What do contrast media add to three-dimensional power
      Doppler evaluation of adnexal masses?" (Croat Med J. 2000;41:257-61).

PMID- 17441226
TI  - [A child with relapsing haemolytic anemia and thrombocytopenia].
AB  - A newborn Norwegian girl of non-consanguineous parents developed petechial
      bleeding, severe thrombocytopenia, and hyperbilirubinemia within 24 hours of
      birth. Severe anemia, macroscopic hematuria, and elevated creatinine developed
      during the first week of life. She was treated with blood transfusions and
      intravenous immunoglobulins. At the age of 9 months, she developed petechiae and
      jaundice during the course of an upper respiratory tract infection, and was
      readmitted to hospital. Thrombocytopenia was discovered and she received
      intravenous immunoglobulins. During the following months the girl was repeatedly
      seen at the paediatric outpatient clinic for petechial bleeding and moderate
      thrombocytopenia. At the age of 20 months, ADAMTS (a metalloprotease-disintegrin
      with thrombospondin type 1 domains)-13 activity was found to be absent. No
      inhibitor was detected in her plasma. Both parents and her younger sister had
      ADAMTS-13 activity of 50 %, establishing the diagnosis of severe congenital
      ADAMTS-13 deficiency. She is now treated with fresh frozen plasma infusions every
      14 days. CONCLUSION: Assay of ADAMTS-13 helps to diagnose a form of thrombotic
      thrombocytopenic purpura which may be managed by prophylactic treatment with
      fresh frozen plasma.

PMID- 17441227
TI  - [Something to learn from--not only for the pediatricians].

PMID- 17441228
TI  - [Portugal soon ready for legal abortion].

PMID- 17441229
TI  - Occurrence of CNS demyelinating disease in patients with myasthenia gravis.

PMID- 17441230
TI  - Occurrence of CNS demyelinating disease in patients with myasthenia gravis.

PMID- 17441231
TI  - Point/counterpoint. Respiratory gating for radiation therapy is not ready for
      prime time.

PMID- 17441232
TI  - Comparison of typical evaluation methods for computer-aided diagnostic schemes:
      Monte Carlo simulation study.
AB  - Computer-aided diagnostic (CAD) schemes have been developed for assisting
      radiologists in the detection of various lesions in medical images. Many
      evaluation approaches, such as the resubstitution, leave-one-out, cross
      validation, and hold-out methods, have been employed for the assessment of the
      performance of various CAD schemes. For these evaluation methods, some
      investigators have studied their bias in the estimated performance levels of CAD
      schemes trained with finite samples. However, systematical study has not been
      conducted for the comparison of these common evaluation methods in terms of
      multiple important characteristics such as the bias of the estimated performance,
      the generalization performance, and the uniqueness of the trained CAD scheme.
      Therefore, in this study, we examined and compared these important
      characteristics for various evaluation methods and attempted to provide a
      guideline for investigators to select appropriate evaluation methods for the
      assessment of CAD schemes in typical practical situations.

PMID- 17441233
TI  - Design of a fast multileaf collimator for radiobiological optimized IMRT with
      scanned beams of photons, electrons, and light ions.
AB  - Intensity modulated radiation therapy is rapidly becoming the treatment of choice
      for most tumors with respect to minimizing damage to the normal tissues and
      maximizing tumor control. Today, intensity modulated beams are most commonly
      delivered using segmental multileaf collimation, although an increasing number of
      radiation therapy departments are employing dynamic multileaf collimation. The
      irradiation time using dynamic multileaf collimation depends strongly on the
      nature of the desired dose distribution, and it is difficult to reduce this time
      to less than the sum of the irradiation times for all individual peak heights
      using dynamic leaf collimation [Svensson et al., Phys. Med. Biol. 39, 37-61
      (1994)]. Therefore, the intensity modulation will considerably increase the total
      treatment time. A more cost-effective procedure for rapid intensity modulation is
      using narrow scanned photon, electron, and light ion beams in combination with
      fast multileaf collimator penumbra trimming. With this approach, the irradiation
      time is largely independent of the complexity of the desired intensity
      distribution and, in the case of photon beams, may even be shorter than with
      uniform beams. The intensity modulation is achieved primarily by scanning of a
      narrow elementary photon pencil beam generated by directing a narrow well focused
      high energy electron beam onto a thin bremsstrahlung target. In the present
      study, the design of a fast low-weight multileaf collimator that is capable of
      further sharpening the penumbra at the edge of the elementary scanned beam has
      been simulated, in order to minimize the dose or radiation response of healthy
      tissues. In the case of photon beams, such a multileaf collimator can be placed
      relatively close to the bremsstrahlung target to minimize its size. It can also
      be flat and thin, i.e., only 15-25 mm thick in the direction of the beam with
      edges made of tungsten or preferably osmium to optimize the sharpening of the
      penumbra. The low height of the collimator will minimize edge scatter from
      glancing incidence. The major portions of the collimator leafs can then be made
      of steel or even aluminum, so that the total weight of the multileaf collimator
      will be as low as 10 kg, which may even allow high-speed collimation in real time
      in synchrony with organ movements. To demonstrate the efficiency of this
      collimator design in combination with pencil beam scanning, optimal
      radiobiological treatments of an advanced cervix cancer were simulated. Different
      geometrical collimator designs were tested for bremsstrahlung, electron, and
      light ion beams. With a 10 mm half-width elementary scanned photon beam and a
      steel collimator with tungsten edges, it was possible to make as effective
      treatments as obtained with intensity modulated beams of full resolution, i.e.,
      here 5 mm resolution in the fluence map. In combination with narrow pencil beam
      scanning, such a collimator may provide ideal delivery of photons, electrons, or
      light ions for radiation therapy synchronized to breathing and other organ
      motions. These high-energy photon and light ion beams may allow three-dimensional
      in vivo verification of delivery and thereby clinical implementation of the
      BioArt approach using Biologically Optimized three-dimensional in vivo predictive
      Assay based adaptive Radiation Therapy [Brahme, Acta Oncol. 42, 123-126 (2003)].

PMID- 17441234
TI  - Impact of Ge-68/Ga-68-based versus CT-based attenuation correction on PET.
AB  - Transmission (Tx) scans are used in PET for attenuation correction (AC). For
      standalone PET this is typically done using Ge-68/Ga-68 sources, for PET-CT using
      CT. Therefore, standalone PET suffers from emission contamination during Tx
      scans, PET-CT does not. Here, we studied the effects of AC across the two
      systems. With a cylindrical phantom (Jaszczak Phantom, Data Spectrum Corp.) with
      hollow spheres (diameter 10-60 mm) two studies were performed. In the first study
      the hollow spheres were filled with 150 kBq/ml FDG and the background with 15
      kBq/ml. In the second study we used 120 kBq/ml in the spheres and 50 kBq/ml in
      the background. Both a low and a high object-to-background ratio are studied this
      way. Multiple scans were acquired on a standalone PET and a PET-CT until 1% of
      the initial concentration remained. Activity concentration in the spheres and
      background was measured from the reconstructed images and compared to the actual
      concentration. For standalone PET, emission scans were reconstructed using hot Tx
      (emission contaminated) and cold Tx (not contaminated). Uniformity within the
      spheres was investigated by profile analysis. For PET-CT, the concentration in
      the big spheres (> 16 mm) was recovered. For the smaller spheres, recovery was
      insufficient due to partial volume effects. For standalone PET the recoveries of
      the spheres (> 16 mm) were 20% (first study) and 13% (second study) lower than
      the actual concentration. Using hot Tx, underestimation of activity concentration
      was up to > 50%. Nonuniformities within the biggest spheres were up to 35%, 12%,
      and 5% (first study), using standalone PET with hot Tx, cold Tx, and using PET
      CT, respectively. Due to contamination of AC by emission photons, standalone PET
      results in a bias in the activity concentration and uniformity. Especially when
      patients get follow-up PET scans on both standalone PET and PET-CT, this may lead
      to misinterpretation.

PMID- 17441235
TI  - Combining two mammographic projections in a computer aided mass detection method.
AB  - A method is presented to improve computer aided detection (CAD) results for
      masses in mammograms by fusing information obtained from two views of the same
      breast. It is based on a previously developed approach to link potentially
      suspicious regions in mediolateral oblique (MLO) and craniocaudal (CC) views.
      Using correspondence between regions, we extended our CAD scheme by building a
      cascaded multiple-classifier system, in which the last stage computes
      suspiciousness of an initially detected region conditional on the existence and
      similarity of a linked candidate region in the other view. We compared the two
      view detection system with the single-view detection method using free-response
      receiver operating characteristic (FROC) analysis and cross validation. The
      dataset used in the evaluation consisted of 948 four-view mammograms, including
      412 cancer cases with a mass, architectural distortion, or asymmetry. A
      statistically significant improvement was found in the lesion based detection
      performance. At a false positive (FP) rate of 0.1 FP/image, the lesion
      sensitivity improved from 56% to 61%. Case based sensitivity did not improve.

PMID- 17441236
TI  - A comparison of the performance of digital mammography systems.
AB  - An objective analysis of image quality parameters was performed for six digital
      mammography systems. The presampled modulation transfer function (MTF),
      normalized noise power spectrum (NNPS), and detective quantum efficiency (DQE)
      for the systems were determined at different doses, for 28 kVp with a Mo/Mo or
      W/Al target/filter combination and 2 mm of additional aluminium filtration. The
      flat-panel units have higher MTF and DQE in the mid to high frequency range than
      standard CR systems. The highest DQE, over the whole dose range, is for the slit
      scanning direct photon counting system. Dual-side read CR can overcome the
      inherent x-ray absorption and signal collection limitations of standard CR
      mammography, improving the low-frequency DQE by 40%, to the same level as full
      field systems, but it does not improve the poor spatial resolution of phosphor.

PMID- 17441237
TI  - Lung metastases detection in CT images using 3D template matching.
AB  - The aim of this study is to demonstrate a novel, fully automatic computer
      detection method applicable to metastatic tumors to the lung with a diameter of 4
      20 mm in high-risk patients using typical computed tomography (CT) scans of the
      chest. Three-dimensional (3D) spherical tumor appearance models (templates) of
      various sizes were created to match representative CT imaging parameters and to
      incorporate partial volume effects. Taking into account the variability in the
      location of CT sampling planes cut through the spherical models, three offsetting
      template models were created for each appearance model size. Lung volumes were
      automatically extracted from computed tomography images and the correlation
      coefficients between the subregions around each voxel in the lung volume and the
      set of appearance models were calculated using a fast frequency domain algorithm.
      To determine optimal parameters for the templates, simulated tumors of varying
      sizes and eccentricities were generated and superposed onto a representative
      human chest image dataset. The method was applied to real image sets from 12
      patients with known metastatic disease to the lung. A total of 752 slices and 47
      identifiable tumors were studied. Spherical templates of three sizes (6, 8, and
      10 mm in diameter) were used on the patient image sets; all 47 true tumors were
      detected with the inclusion of only 21 false positives. This study demonstrates
      that an automatic and straightforward 3D template-matching method, without any
      complex training or postprocessing, can be used to detect small lung metastases
      quickly and reliably in the clinical setting.

PMID- 17441238
TI  - Effects of organ motion on IMRT treatments with segments of few monitor units.
AB  - Interplay between organ (breathing) motion and leaf motion has been shown in the
      literature to have a small dosimetric impact for clinical conditions (over a 30
      fraction treatment). However, previous studies did not consider the case of
      treatment beams made up of many few-monitor-unit (MU) segments, where the segment
      delivery time (1-2 s) is of the order of the breathing period (3-5 s). In this
      study we assess if breathing compromises the radiotherapy treatment with IMRT
      segments of low number of MUs. We assess (i) how delivered dose varies, from
      patient to patient, with the number of MU per segment, (ii) if this delivered
      dose is identical to the average dose calculated without motion over the path of
      the motion, and (iii) the impact of the daily variation of the delivered dose as
      a function of MU per segment. The organ motion was studied along two orthogonal
      directions, representing the left-right and cranial-caudal directions of organ
      movement for a patient setup in the supine position. Breathing motion was modeled
      as sin(x), sin4(x), and sin6(x), based on functions used in the literature to
      represent organ motion. Measurements were performed with an ionization chamber
      and films. For a systematic study of motion effects, a MATLAB simulation was
      written to model organ movement and dose delivery. In the case of a single beam
      made up of one single segment, the dose delivered to point in a moving target
      over 30 fractions can vary up to 20% and 10% for segments of 10 MU and 20 MU,
      respectively. This dose error occurs because the tumor spends most of the time
      near the edges of the radiation beam. In the case of a single beam made of
      multiple segments with low MU, we observed 2.4%, 3.3%, and 4.3% differences,
      respectively, for sin(x), sin4(x), and sin6(x) motion, between delivered dose and
      motion-averaged dose for points in the penumbra region of the beam and over 30
      fractions. In approximately 5-10% of the cases, differences between the motion
      averaged dose and the delivered 30-fraction dose could reach 6%, 8% and 10-12%,
      respectively for sin(x), sin4(x), and sin6(x) motion. To analyze a clinical IMRT
      beam, two patient plans were randomly selected. For one of the patients, the
      beams showed a likelihood of up to 25.6% that the delivered dose would deviate
      from the motion-averaged dose by more than 1%. For the second patient, there was
      a likelihood of up to 62.8% of delivering a dose that differs by more than 1%
      from the motion-averaged dose and a likelihood of up to approximately 30% for a
      2% dose error. For the entire five-beam IMRT plan, statistical averaging over the
      beams reduces the overall dose error between the delivered dose and the motion
      averaged dose. For both patients there was a likelihood of up to 7.0% and 33.9%
      that the dose error was greater than 1%, respectively. For one of the patients,
      there was a 12.6% likelihood of a 2% dose error. Daily intrafraction variation of
      the delivered dose of more than 10% is non-negligible and can potentially lead to
      biological effects. We observed [for sin(x), sin4(x), and sin6(x)] that below 10
      15 MU leads to large daily variations of the order of 15-35%. Therefore, for
      small MU segments, non-negligible biological effects can be incurred. We conclude
      that for most clinical cases the effects may be small because of the use of many
      beams, it is desirable to avoid low-MU segments when treating moving targets. In
      addition, dose averaging may not work well for hypo-fractionation, where fewer
      fractions are used. For hypo-fractionation, PDF modeling of the tumor motion in
      IMRT optimization may not be adequate.

PMID- 17441239
TI  - Two-dimensional iterative region-of-interest (ROI) reconstruction from truncated
      projection data.
AB  - A small detector or limited gantry rotation angles may cause data truncation, in
      which case the entire object cannot be completely reconstructed. However, a small
      region of interest (ROI) may be recoverable in certain truncation situations. Two
      analytical methods have been proposed for exact ROI reconstruction. Here we
      evaluate the capability of ROI reconstruction using an maximum-likelihood
      expectation-maximization (ML-EM) method, which directly solves the inverse
      problem of the system equations. ROI reconstruction using the ML-EM method is
      compared with that using the two analytical methods. Comparisons are based on
      reconstructions of four specifically designed, computer-simulated truncation
      cases. In the simulation, each reconstructed ROI is coupled with its counterpart
      in the nontruncated case to evaluate the accuracy of the reconstructed ROI. We
      found that, (a) in two truncation situations the ROI can be reconstructed by both
      the analytical methods and the two-dimensional ML-EM method, but the ML-EM method
      may produce a larger ROI; (b) for a truncation case [Fig. 3(c)] that neither
      analytical algorithm is applicable, the ML-EM method provides a quantitative ROI
      reconstruction; and (c) for the well-known "interior" truncation problem, neither
      the analytical methods nor the ML-EM method can perform an exact ROI
      reconstruction, but the ML-EM method provides informative ROI images. We also
      propose an analysis using the truncated projection matrix and its Moore-Penrose
      inverse matrix which can help to determine the recoverable ROI using iterative
      methods for a given truncation situation.

PMID- 17441240
TI  - A 4 x 500 mm2 cloverleaf detector system for in vivo bone lead measurement.
AB  - A 4 x 500 mm2 "cloverleaf" low energy germanium detector array has been assembled
      for the purpose of in vivo bone lead measurement through x-ray fluorescence.
      Using 109Cd as an exciting source, results are reported from a leg phantom
      simulating measurement of lead in a human tibia. For high activity (4.0-4.4 GBq)
      and low activity (0.18-0.19 GBq) sources, measurement results are reported for
      both the cloverleaf system and a conventional single detector system of
      equivalent surface area (2000 mm2). The mean uncertainty and reproducibility of
      measurement were both significantly improved for the cloverleaf system with a
      high activity 109Cd source. When using a source activity of 4.4 GBq, measurement
      of the phantom resulted in an average bone lead uncertainty of 0.79 microg/g and
      a reproducibility of 0.84 microg/g. These results represent the highest precision
      yet reported from a bone lead x-ray fluorescence system.

PMID- 17441241
TI  - Absolute dose measurements by means of a small cylindrical ionization chamber for
      very high dose per pulse high energy electron beams.
AB  - Very high dose per pulse (3-13 cGy/pulse) high energy electron beams are
      currently produced by special linear accelerators (linac) dedicated to Intra
      Operative Radiation Therapy (IORT). The electron beams produced by such linacs
      are collimated by special Perspex applicators of various size and cylindrically
      shaped. The biggest problems from the dosimetric point of view are caused by the
      high dose-per-pulse values and the use of inclined applicators. In this work
      measurements of absolute dose for the inclined applicators were done by using a
      small cylindrical ionization chamber, type CC01 (Wellhofer), a parallel plane
      ionization chamber type Markus (PTW 23343) and radiochromic films type EBT. We
      show a method which allows calculating the quality correction factors for CC01
      chamber with an uncertainty of 1% and the absolute dose value for the inclined
      applicators using CC01 with an uncertainty of 3.1% for electron beams of energy
      of 6 and 7 MeV produced by the linac dedicated to IORT Novac7.

PMID- 17441242
TI  - On the influence of noise correlations in measurement data on basis image noise
      in dual-energylike x-ray imaging.
AB  - In conventional dual-energy systems, two transmission measurements with distinct
      spectral characteristics are performed. These measurements are used to obtain the
      line integrals of two basis material densities. Usually, the measurement process
      is such that the two measured signals can be treated as independent and therefore
      uncorrelated. Recently, however, a readout system for x-ray detectors has been
      introduced for which this is no longer the case. The readout electronics is
      designed to obtain simultaneous measurements of the total number of photons N and
      the total energy E they deposit in the sensor material. Practically, this is
      realized by a signal replication and separate counting and integrating processing
      units. Since the quantities N and E are (electronically) derived from one and the
      same physical sensor signal, they are statistically correlated. Nevertheless, the
      pair N and E can be used to perform a dual-energy processing following the well
      known approach by Alvarez and Macovski. Formally, this means that N is to be
      identified with the first dual-energy measurement M1 and E with the second
      measurement M2. In the presence of input correlations between M1 = N and M2 = E,
      however, the corresponding analytic expressions for the basis image noise have to
      be modified. The main observation made in this paper is that for positively
      correlated data, as is the case for the simultaneous counting and integrating
      device mentioned above, the basis image noise is suppressed through the influence
      of the covariance between the two signals. We extend the previously published
      relations for the basis image noise to the case where the original measurements
      are not independent and illustrate the importance of the input correlations by
      comparing dual-energy basis image noise resulting from the device mentioned above
      and a device measuring the photon numbers and the deposited energies
      consecutively.

PMID- 17441243
TI  - Three-dimensional reconstruction of seed implants by randomized rounding and
      visual evaluation.
AB  - The development of efficient 3D seed reconstruction algorithms is an ongoing and
      vivid research topic. Since the 1980s many publications about seed assignment
      were published. In this paper a novel mathematical approach is described to solve
      the 3D assignment problem for the reconstruction of seeds with radiographs: we
      present a fast linear programming approach together with afterwards applying the
      so-called randomized rounding scheme to compute good (possibly partial)
      assignments. We apply a visualization software that allows user interaction to
      check the solution given by the algorithm and to augment partial assignments. The
      second step is justified as the randomized algorithm already returns optimal
      solutions is many cases, and in cases with partial assignments it fails to match
      only a very small number of seed images. Our algorithm transfers ideas from
      recent breakthrough research work on the design of efficient randomized
      algorithms in discrete optimization and computer science to the seed
      reconstruction problem.

PMID- 17441244
TI  - X-ray imaging using avalanche multiplication in amorphous selenium: investigation
      of depth dependent avalanche noise.
AB  - The past decade has seen the swift development of the flat-panel detector (FPD),
      also known as the active matrix flat-panel imager, for digital radiography. This
      new technology is applicable to other modalities, such as fluoroscopy, which
      require the acquisition of multiple images, but could benefit from some
      improvements. In such applications where more than one image is acquired less
      radiation is available to form each image and amplifier noise becomes a serious
      problem. Avalanche multiplication in amorphous selenium (a-Se) can provide the
      necessary amplification prior to read out so as to reduce the effect of
      electronic noise of the FPD. However, in direct conversion detectors avalanche
      multiplication can lead to a new source of gain fluctuation noise called depth
      dependent avalanche noise. A theoretical model was developed to understand depth
      dependent avalanche noise. Experiments were performed on a direct imaging system
      implementing avalanche multiplication in a layer of a-Se to validate the theory.
      For parameters appropriate for a diagnostic imaging FPD for fluoroscopy the
      detective quantum efficiency (DQE) was found to drop by as much as 50% with
      increasing electric field, as predicted by the theoretical model. This drop in
      DQE can be eliminated by separating the collection and avalanche regions. For
      example by having a region of low electric field where x rays are absorbed and
      converted into charge that then drifts into a region of high electric field where
      the x-ray generated charge undergoes avalanche multiplication. This means quantum
      noise limited direct conversion FPD for low exposure imaging techniques are a
      possibility.

PMID- 17441246
TI  - Determination of x-ray spectra from attenuation data by imposing a priori
      positiveness and bounded support: theory and experimental validation.
AB  - The determination of the spectral distribution of an x-ray beam from attenuation
      measurements in a narrow beam has aroused great interest since it was first
      proposed by Silberstein in 1932. Since then, it has become clear that this is an
      ill-conditioned problem. Then, due to the intrinsic difficulties of the problem,
      care has been taken to improve the mathematical and numerical inversion
      techniques. Alternative ways to circumvent the explicit inversion by using the
      attenuation curve itself to calculate directly generalized moments of the
      solution have also been found. In this work, the explicit reconstruction of the
      spectral distribution is carried out by an expectation-maximization method that
      satisfies the a priori condition of positiveness of the solution and allows us to
      impose the boundness of its support easily, conditions which are known to be
      fulfilled by physically acceptable solutions. The simulations made and the
      experimental validation of the proposed method allow us to prove its scope and
      limitations.

PMID- 17441245
TI  - The multi-module, multi-resolution system (M3R): a novel small-animal SPECT
      system.
AB  - We have designed and built an inexpensive, high-resolution, tomographic imaging
      system, dubbed the multi-module, multi-resolution system, or M3R. Slots machined
      into the system shielding allow for the interchange of pinhole plates, enabling
      the system to operate over a wide range of magnifications and with virtually any
      desired pinhole configuration. The flexibility of the system allows system
      optimization for specific imaging tasks and also allows for modifications
      necessary due to improved detectors, electronics, and knowledge of system
      construction (e.g., system sensitivity optimization). We provide an overview of
      M3R, focusing primarily on system design and construction, aperture construction,
      and calibration methods. Reconstruction algorithms will be described and
      reconstructed images presented.

PMID- 17441247
TI  - Measurement of Gamma Knife helmet factors using MOSFETs.
AB  - The relative dose rate for the different Gamma Knife helmets (4, 8, 14, and 18
      mm) is characterized by their respective helmet factors. Since the plateau of the
      dose profile for the 4 mm helmet is at most 1 mm wide, detector choices are
      limited. Traditionally helmet factors have been measured using 1 x 1 x 1 mm3
      thermoluminescent dosimeters (TLDs). However, these are time-consuming,
      cumbersome measurements. This article investigates the use of metal-oxide
      semiconductor field effect transistors (MOSFETs) (active area of 0.2 x 0.2 mm2)
      as a more accurate and convenient dosimeter. Their suitability for these
      measurements was confirmed by basic characterization measurements. Helmet factors
      were measured using both MOSFETs and the established TLD approach. A custom
      MOSFET cassette was designed in analogy to the Elekta TLD cassette (Elekta
      Instruments AB) for use with the Elekta dosimetry sphere. Although both
      dosimeters provided values within 3% of the manufacturer's suggestion, MOSFETs
      provided superior accuracy and precision, in a fraction of the time required for
      the TLD measurements. Thus, MOSFETs proved to be a reasonable alternative to TLDs
      for performing helmet factor measurements.

PMID- 17441248
TI  - An anatomically realistic lung model for Monte Carlo-based dose calculations.
AB  - Treatment planning for disease sites with large variations of electron density in
      neighboring tissues requires an accurate description of the geometry. This self
      evident statement is especially true for the lung, a highly complex organ having
      structures with a wide range of sizes that range from about 10(-4) to 1 cm. In
      treatment planning, the lung is commonly modeled by a voxelized geometry obtained
      using computed tomography (CT) data at various resolutions. The simplest such
      model, which is often used for QA and validation work, is the atomic mix or mean
      density model, in which the entire lung is homogenized and given a mean (volume
      averaged) density. The purpose of this paper is (i) to describe a new
      heterogeneous random lung model, which is based on morphological data of the
      human lung, and (ii) use this model to assess the differences in dose
      calculations between an actual lung (as represented by our model) and a mean
      density (homogenized) lung. Eventually, we plan to use the random lung model to
      assess the accuracy of CT-based treatment plans of the lung. For this paper, we
      have used Monte Carlo methods to make accurate comparisons between dose
      calculations for the random lung model and the mean density model. For four
      realizations of the random lung model, we used a single photon beam, with two
      different energies (6 and 18 MV) and four field sizes (1 x 1, 5 x 5, 10 x 10, and
      20 x 20 cm2). We found a maximum difference of 34% of D(max) with the 1 x 1, 18
      MV beam along the central axis (CAX). A "shadow" region distal to the lung, with
      dose reduction up to 7% of D(max), exists for the same realization. The dose
      perturbations decrease for larger field sizes, but the magnitude of the
      differences in the shadow region is nearly independent of the field size. We also
      observe that, compared to the mean density model, the random structures inside
      the heterogeneous lung can alter the shape of the isodose lines, leading to a
      broadening or shrinking of the penumbra region. For small field sizes, the mean
      lung doses significantly depend on the structures' relative locations to the
      beam. In addition to these comparisons between the random lung and mean density
      models, we also provide a preliminary comparison between dose calculations for
      the random lung model and a voxelized version of this model at 0.4 x 0.4 x 0.4
      cm3 resolution. Overall, this study is relevant to treatment planning for lung
      tumors, especially in situations where small field sizes are used. Our results
      show that for such situations, the mean density model of the lung is inadequate,
      and a more accurate CT model of the lung is required. Future work with our model
      will involve patient motion, setup errors, and recommendations for the resolution
      of CT models.

PMID- 17441249
TI  - Monte Carlo simulations of absorbed dose in a mouse phantom from 18-fluorine
      compounds.
AB  - The purpose of this study was to calculate internal absorbed dose distribution in
      mice from pre-clinical small animal PET imaging procedures with fluorine-18
      labeled compounds (18FDG, 18FLT, and fluoride ion). The GATE Monte Carlo software
      and a realistic, voxel-based mouse phantom that included a subcutaneous tumor
      were used to perform simulations. Discretized time-activity curves obtained from
      dynamic in vivo studies with each of the compounds were used to set the activity
      concentration in the simulations. For 18FDG, a realistic range of uptake ratios
      was considered for the heart and tumor. For each simulated time frame, the
      biodistribution of the radionuclide in the phantom was considered constant, and a
      sufficient number of decays were simulated to achieve low statistical
      uncertainty. Absorbed dose, which was scaled to take into account radioactive
      decay, integration with time, and changes in biological distribution was reported
      in mGy per MBq of administered activity for several organs and uptake scenarios.
      The mean absorbed dose ranged from a few mGy/MBq to hundreds of mGy/MBq. Major
      organs receive an absorbed dose in a range for which biological effects have been
      reported. The effects on a given investigation are hard to predict; however,
      investigators should be aware of potential perturbations especially when the
      studied organ receives high absorbed dose and when longitudinal imaging protocols
      are considered.

PMID- 17441251
TI  - Comparison of local and global angular interpolation applied to spectral-spatial
      EPR image reconstruction.
AB  - Spectral-spatial images reconstructed from a small number of projections suffer
      from streak artifacts that are seen as noise, particularly in the spectral
      dimension. Interpolation in projection space can reduce artifacts in the
      reconstructed images. The reduction of background artifacts improves lineshape
      fitting. In this work, we compared the performances of angular interpolation
      implemented using linear, cubic B-spline, and sinc methods. Line width maps were
      extracted from 4-D EPR images of phantoms using spectral fitting to evaluate each
      interpolation method and its robustness to noise. Results from experiment and
      simulation showed that the cubic B-spline, angular interpolation was preferable
      to either sinc or linear interpolation methods.

PMID- 17441250
TI  - Ultrasonic tissue characterization via 2-D spectrum analysis: theory and in vitro
      measurements.
AB  - A theoretical model is described for application in ultrasonic tissue
      characterization using a calibrated 2-D spectrum analysis method. This model
      relates 2-D spectra computed from ultrasonic backscatter signals to intrinsic
      physical properties of tissue microstructures, e.g., size, shape, and acoustic
      impedance. The model is applicable to most clinical diagnostic ultrasound
      systems. Two experiments employing two types of tissue architectures, spherical
      and cylindrical scatterers, are conducted using ultrasound with center
      frequencies of 10 and 40 MHz, respectively. Measurements of a tissue-mimicking
      phantom with an internal suspension of microscopic glass beads are used to
      validate the theoretical model. Results from in vitro muscle fibers are presented
      to further elucidate the utility of 2-D spectrum analysis in ultrasonic tissue
      characterization.

PMID- 17441253
TI  - Automatic determination of primary electron beam parameters in Monte Carlo
      simulation.
AB  - In order to obtain realistic and reliable Monte Carlo simulations of medical
      linac photon beams, an accurate determination of the parameters that define the
      primary electron beam that hits the target is a fundamental step. In this work we
      propose a new methodology to commission photon beams in Monte Carlo simulations
      that ensures the reproducibility of a wide range of clinically useful fields. For
      such purpose accelerated Monte Carlo simulations of 2 x 2, 10 x 10, and 20 x 20
      cm2 fields at SSD = 100 cm are carried out for several combinations of the
      primary electron beam mean energy and radial FWHM. Then, by performing a
      simultaneous comparison with the correspondent measurements for these same
      fields, the best combination is selected. This methodology has been employed to
      determine the characteristics of the primary electron beams that best reproduce a
      Siemens PRIMUS and a Varian 2100 CD machine in the Monte Carlo simulations.
      Excellent agreements were obtained between simulations and measurements for a
      wide range of field sizes. Because precalculated profiles are stored in
      databases, the whole commissioning process can be fully automated, avoiding
      manual fine-tunings. These databases can also be used to characterize any
      accelerators of the same model from different sites.

PMID- 17441252
TI  - An objective method for combining multi-parametric MRI datasets to characterize
      malignant tumors.
AB  - Medical imaging has made significant contributions to the characterization of
      malignant tumors. In many cases, however, maps from multiple modalities may be
      required for more complete tumor mapping. In this manuscript we propose an
      objective method for combining multiple imaging datasets with the goal of
      characterizing malignant tumors. We refer to the proposed technique as the
      percent overlap method (POM). To demonstrate the power and flexibility of the POM
      analysis, we present four patients with recurrent glioblastoma multiforme. Each
      patient had multiple magnetic resonance imaging procedures resulting in seven
      different parameter maps. Chemical shift imaging was used to provide three
      metabolite ratio maps (Cho:NAA, Cho:Cre, Lac:Cre). A perfusion scan provided
      regional cerebral blood volume and permeability maps. Diffusion and carbogen
      based hypoxia mapping data were also acquired. Composite maps were formed for
      each patient using POM, then were compared to results from the ISODATA clustering
      technique. The POM maps of likely recurrent tumor regions were found to be
      consistent with the ISODATA clustering method. This manuscript presents an
      objective method for combining parameters from multiple physiologic imaging
      techniques into a single composite map. The accuracy of the map depends strongly
      on the sensitivity of the chosen imaging parameters to the disease process at the
      time of image acquisition. Further validation of this method may be achieved by
      correlation with histological data.

PMID- 17441254
TI  - Design study of a raster scanning system for moving target irradiation in heavy
      ion radiotherapy.
AB  - A project to construct a new treatment facility as an extension of the existing
      heavy-ion medical accelerator in chiba (HIMAC) facility has been initiated for
      further development of carbon-ion therapy. The greatest challenge of this project
      is to realize treatment of a moving target by scanning irradiation. For this
      purpose, we decided to combine the rescanning technique and the gated irradiation
      method. To determine how to avoid hot and/or cold spots by the relatively large
      number of rescannings within an acceptable irradiation time, we have studied the
      scanning strategy, scanning magnets and their control, and beam intensity dynamic
      control. We have designed a raster scanning system and carried out a simulation
      of irradiating moving targets. The result shows the possibility of practical
      realization of moving target irradiation with pencil beam scanning. We describe
      the present status of our design study of the raster scanning system for the
      HIMAC new treatment facility.

PMID- 17441255
TI  - A computer simulation platform for the optimization of a breast tomosynthesis
      system.
AB  - In breast tomosynthesis there is a compromise between resolution, noise, and
      acquisition speed for a given glandular dose. The purpose of the present work is
      to develop a simulation platform to investigate the potential imaging performance
      for the many possible tomosynthesis system configurations. The simulation
      platform was used to investigate the dependence of image blur and signal
      difference to noise ratio (SDNR) for several different tomosynthesis acquisition
      configurations. Simulated projections of a slanted thin tungsten wire placed in
      different object planes were modified according to the detector's modulation
      transfer function (MTF), with or without pixel binning. In addition, the focal
      spot blur (FSB), which depends on the location of the wire, the system geometry,
      the source-detector movement speed, and the exposure time, was also incorporated
      into the projections. Both expectation maximization (EM) and filtered back
      projection (FBP) based algorithms were used for 3D image reconstruction. The in
      plane MTF was calculated from the reconstructed image of the wire. To evaluate
      the noise performance, simulated noiseless projections of calcification and tumor
      in uniform breast tissue were modified with the noise power spectrum (NPS)
      calculated from a cascaded linear system model for the detector for a given x-ray
      dose. The SDNR of the reconstructed images was calculated with different
      tomosynthesis configurations, e.g., pixel binning, view number, and angular
      range. Our results showed that for a source-to-imager distance (SID) of 66 cm,
      pixel binning (2 x 2) caused more degradation to the in-plane MTF than the blur
      caused by the moving focal spot and reconstruction. The in-depth resolution can
      be improved by increasing the angular range.

PMID- 17441256
TI  - Spatial autocorrelation and mean intercept length analysis of trabecular bone
      anisotropy applied to in vivo magnetic resonance imaging.
AB  - Osteoporosis is characterized by bone loss and deterioration of the trabecular
      bone (TB) architecture that leads to impaired overall mechanical strength of the
      bone. Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry is
      currently the standard clinical metric assessing bone integrity but it fails to
      capture the structural changes in the TB. Recent research suggests that structure
      contributes to bone strength in a manner complementary to BMD. Besides parameters
      of scale such as the mean TB thickness and mean bone volume fraction, parameters
      describing the anisotropy of the trabecular architecture play an important role
      in the characterization of TB since trabeculae are preferentially oriented along
      the direction of local loading. Therefore, the degree of structural anisotropy is
      of pivotal importance to the bone's mechanical competence. The most common method
      for measuring structural anisotropy of TB is the mean-intercept length (MIL). In
      this work we present a method, based on the three-dimensional spatial
      autocorrelation function (ACF), for mapping of the full structural anisotropy
      ellipsoid of both TB thickness and spacing and we examine its performance as
      compared to that of MIL. Not only is the ACF method faster by several orders of
      magnitude, it is also considerably more robust to noise. Further, it is
      applicable at lower spatial resolution and is relatively insensitive to image
      shading. The chief reason for ACF's superior performance is that it does not
      require binarization, which is difficult to achieve in the limited spatial regime
      of in vivo magnetic resonance imaging. MIL and ACF have been applied to high
      resolution magnetic resonances images of the tibia in a group of ten healthy
      postmenopausal women by comparing the structural anisotropy and principal
      direction of the computed fabric tensor for each method. While there is fair
      agreement between the two methods, ACF analysis yielded greater anisotropy than
      MIL for both TB thickness and spacing. There was good agreement between the two
      techniques as far as the eigenvectors of the fabric ellipsoids were concerned,
      which parallel the bone's macroscopic axis.

PMID- 17441258
TI  - Comment on "In vivo cancer diagnosis with optical spectroscopy and acoustically
      induced blood stasis using a murine Mca35 model," [Med. Phys. 33, 1623-1633
      (2006)].

PMID- 17441257
TI  - Breast in vivo dosimetry by a portal ionization chamber.
AB  - This work reports a practical method for the determination of the in vivo breast
      middle dose value, D(m) on the beam central axis, using a signal S(t), obtained
      by a small thimble ion chamber positioned at the center of the electronic portal
      imaging device, and irradiated by the x-ray beam transmitted through the patient.
      The use of a stable ion chamber reduces many of the disadvantages associated with
      the use of diodes as their periodic recalibration and positioning is time
      consuming. The method makes use of a set of correlation functions obtained by the
      ratios S(t)/D(m), determined by irradiating cylindrical water phantoms with
      different diameters. The method proposed here is based on the determination of
      the water-equivalent thickness of the patient, along the beam central axis, by
      the treatment planning system that makes use of the electron densities obtained
      by a computed tomography scanner. The method has been applied for the breast in
      vivo dosimetry of ten patients treated with a manual intensity modulation with
      four asymmetric beams. In particular, two tangential rectangular fields were
      first delivered, thereafter a fraction of the dose (typically less than 10%) was
      delivered with two multi leaf-shaped beams which included only the mammarian
      tissue. Only the two rectangular fields were tested and for every checked field
      five measurements were carried out. Applying a continuous quality assurance
      program based on the tests of patient setup, machine settings and dose planning,
      the proposed method is able to verify agreements between the computed dose
      D(m,TPS) and the in vivo dose value D(m), within 4%.

PMID- 17441259
TI  - Correction: Standard HR.1.20, element of performance 8 for hospitals.

PMID- 17441260
TI  - Update: information about obtaining a CLIA certificate.

PMID- 17441261
TI  - A better way to predict cardiovascular risk. We know how important cholesterol
      levels are, but what about inflammation?

PMID- 17441262
TI  - Cognitive behavioral therapy helps ease tinnitus discomforts.

PMID- 17441263
TI  - Even mildly impaired kidney function can affect bone health.

PMID- 17441264
TI  - What to do about tennis elbow. There's surprisingly little evidence about what's
      best.

PMID- 17441265
TI  - Sunscreens. New wave in sun protection: blocking ultraviolet A.

PMID- 17441266
TI  - C. difficile-associated disease on the rise. A newly recognized strain of a
      bacterium found mostly in hospitals is causing more illness.

PMID- 17441267
TI  - By the way, doctor. I'm a healthy 65-year-old woman and just had my first bone
      density test. How often do I need to have it repeated?

PMID- 17441268
TI  - DHEA and health: more questions than answers.

PMID- 17441269
TI  - Pomegranates for the prostate and the heart: seeds of hope.

PMID- 17441270
TI  - Medical memo: high-dose radiotherapy for prostate cancer.

PMID- 17441271
TI  - On call. My 27-year-old son had his left testicle removed to treat testicular
      cancer. He's doing beautifully, and his doctors are confident that he is cured.
      We are all delighted, but we worry that he may develop cancer in his right
      testicle. What are the chances of a second cancer? And what should we do about
      it?

PMID- 17441272
TI  - Stalking vulnerable plaque: researchers are closing in. Identifying plaque would
      enable lifesaving preventive treatment.

PMID- 17441273
TI  - Community-acquired infections: medical and publish health sectors concerned. You
      could be a handshake away from a staph infection. But there are simple preventive
      measures you can take.

PMID- 17441275
TI  - Exercise doesn't cause knee OA. It's OK to start or continue exercising to reduce
      your symptoms of knee osteoarthritis.

PMID- 17441274
TI  - Meds hiatus won't hurt your hips. Five years on, five years off: taking a break
      from Fosamax won't result in broken bones.

PMID- 17441276
TI  - Curing prostate cancer--without surgery. Combo radiation therapies enable
      prostate retention, low risk of incontinence and impotence.

PMID- 17441277
TI  - Three factors can predict risk of self-neglect in older adults. Memory,
      organization, and reasoning are measures of the capacity to care properly for
      oneself.

PMID- 17441278
TI  - I take acetaminophen to help with my arthritis pain. Is it okay for me to drink
      wine while I'm taking this medication?

PMID- 17441279
TI  - Arctic vegetation damage by winter-generated coal mining pollution released upon
      thawing.
AB  - Acid mine drainage (known as AMD) is a well-known environmental problem resulting
      from the oxidation of sulfidic mine waste. In cold regions, AMD is often
      considered limited by low temperatures most of the year and observed
      environmental impact is related to pollution generated during the warm summer
      period. Here we show that heat generation within an oxidizing, sulfidic, coal
      mining waste-rock pile in Svalbard (78 degrees N) is high enough to keep the pile
      warm (roughly 5 degrees C throughout the year) despite mean annual air
      temperatures below -5 degrees C. Consequently, weathering processes continue year
      round within the waste-rock pile. During the winter, weathering products
      accumulate within the pile because of a frozen outer layer on the pile and are
      released as a flush within 2 weeks of soil thawing in the spring. Consequently,
      spring runoff water contains elevated concentrations of metals. Several of these
      metals are taken up and accumulated in plants where they reach phytotoxic levels,
      including aluminum and manganese. Laboratory experiments document that uptake of
      Al and Mn in native plant species is highly correlated with dissolved
      concentrations. Therefore, future remedial actions to control the adverse
      environmental impacts of cold region coal-mining need to pay more attention to
      winter processes including AMD generation and accumulation of weathering
      products.

PMID- 17441280
TI  - Theoretically speaking. David Clary talks molecular quantum dynamics with Hilary
      Crichton.

PMID- 17441281
TI  - Delivering the goods.

PMID- 17441282
TI  - [Prejudice and evidence, oppositions and convergencies in today's psychiatry].
AB  - The notion of prejudice in epistemology starts in the early times of modern
      thought, together with the first reflections on science. Tracks of the notion of
      prejudice can be followed right up to our own days, all throughout the succession
      of epistemologies, with such notion always opposed to the notion of evidence.
      However, what in one epistemology stands for prejudice, is labeled as evidence in
      subsequent epistemologies, and the other way round. The present work aims at
      demonstrating the multivocal character of the evidence-prejudice schemas, and at
      critically reconsidering its use in present psychiatry.

PMID- 17441283
TI  - A systematic future? Interview by Katherine Vickers.

PMID- 17441284
TI  - The soft cell.

PMID- 17441285
TI  - [Prejudice and stigma in psychiatry].

PMID- 17441286
TI  - Readers' and author's responses to "Physicians of the future will use online
      content to guide their decisions. The future is now!".

PMID- 17441287
TI  - Readers respond to "Readers respond to 'End the war on obesity: make peace with
      your patients' ".

PMID- 17441288
TI  - Reader's response to "nuclear mutagenesis".

PMID- 17441289
TI  - BoNT/E prevents seizure-induced activation of caspase 3 in the rat hippocampus.
AB  - Clinical and experimental studies clearly demonstrate that prolonged seizures and
      status epilepticus induce neuronal cell death in the brain. Recent evidence
      suggests that induction of apoptosis contributes greatly to seizure-induced brain
      damage. We recently demonstrated that intrahippocampal delivery of botulinum
      neurotoxin E (BoNT/E) in the rat hippocampus is able to prevent neuronal loss,
      which occurs after kainic-acid-induced seizures. Here, we investigated the
      molecular mechanisms of BoNT/E-mediated neuroprotection. We found that
      intrahippocampal administration of BoNT/E prevents the upregulation of apoptotic
      proteins (phosphorylated c-Jun and cleaved caspase 3), which occurs in
      hippocampal neurones following kainic acid seizures. These results demonstrate
      that the neuroprotective action of BoNT/E on seizure-injured hippocampal neurons
      involves the blockade of well-characterized apoptotic pathways.

PMID- 17441290
TI  - Reader's response to "Rapid and complete control of idiopathic hypereosinophilia
      with imatinib mesylate".

PMID- 17441291
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17441292
TI  - Predictors of an accurate preoperative sestamibi scan for single-gland
      parathyroid adenomas.
AB  - OBJECTIVE: To investigate why some patients with single parathyroid adenomas have
      negative preoperative sestamibi scans. DESIGN: Retrospective review. SETTING:
      Tertiary care center. PATIENTS: Twenty-one patients with false-negative (FN)
      scans were compared with 22 patients with true-positive (TP) scans. All patients
      had single parathyroid adenomas. INTERVENTIONS: Neck exploration and removal of
      parathyroid adenomas. MAIN OUTCOME MEASURES: Age; sex; preoperative serum calcium
      and parathyroid hormone levels; gland weight; location; and pathologic features.
      RESULTS: There was no significant difference in age or preoperative serum calcium
      or parathyroid hormone levels. Gland weight was greater in the TP group compared
      with the FN group (mean +/- SD, 1336 +/- 1603 mg vs 475 +/- 365 mg; P = .04); 13
      (62%) of the 21 glands in the FN group were located in the upper position,
      compared with 6 (27%) of the 22 glands in the TP group (P = .03). Ten of the 22
      glands in the TP group consisted predominantly of oxyphil cells, compared with 2
      of the 21 glands in the FN group (P = .02). A multivariate logistic regression
      model yielded the following factors that predicted an accurate scan: higher
      percentage of oxyphil cells (P = .03), heavier gland (P = .03), female sex (P =
      .04), and gland location in the lower position (P = .04). CONCLUSIONS: Smaller
      volume parathyroid adenomas and those in the upper position are less likely to be
      localized with sestamibi scans. A TP scan correlates with oxyphil cell
      predominance, supporting a role for the mitochondrial-rich cell in sestamibi
      uptake and retention.

PMID- 17441294
TI  - Reader's response and author's reply to "A survey of neurologists on bothersome
      patient behaviors".

PMID- 17441293
TI  - National outcomes after gastric resection for neoplasm.
AB  - HYPOTHESIS: That factors affecting outcomes of surgical resection in the
      treatment of gastric cancer can be identified using a large US database. DESIGN:
      Retrospective observational study. SETTING: The Nationwide Inpatient Sample from
      January 1, 1998, through December 31, 2003. PATIENTS: We included 13 354 patient
      discharges (approximately 66 096 nationally by weighted analysis) who underwent
      gastric resection for neoplasm. MAIN OUTCOME MEASURE: In-hospital mortality.
      Univariate analyses were performed by means of chi(2) tests. A multivariate
      logistic regression was performed to determine which variables were independently
      predictive of in-hospital mortality. RESULTS: During the study period, 50 738
      patients (approximately 250 420 nationally) were discharged with the diagnosis of
      gastric neoplasm. Of those, 13 354 (26.3%) underwent gastric resection during
      their hospitalization. In-hospital mortality for patients undergoing surgery was
      6.0%, without significant change from 1998 through 2003. Factors predictive of
      significantly increased in-hospital mortality included low annual hospital
      surgical volume (lowest [<or= 4 gastrectomies per year] vs highest [>or= 11
      gastrectomies per year], 6.8% vs 4.9%; adjusted odds ratio [OR], 1.5; 95%
      confidence interval [CI], 1.2-1.8]), older patient age (50-69 vs <50 years, 4.0%
      vs 2.1%; adjusted OR, 1.5; 95% CI, 1.1-2.2) (>or =70 vs <50 years, 8.6% vs 2.1%;
      adjusted OR, 2.9; 95% CI, 2.0-4.3), male sex (male vs female, 6.7% vs 5.0%;
      adjusted OR, 1.3; 95% CI, 1.1-1.5), and procedure type (total gastrectomy vs all
      other resections, 8.0% vs 5.3%; adjusted OR, 1.4; 95% CI, 1.2-1.7). CONCLUSIONS:
      Higher annual surgical volume is predictive of lower in-hospital mortality for
      patients undergoing gastric resection for neoplasm. Other factors significantly
      associated with superior outcomes after gastric resection included diagnosis
      type, procedure type, younger age, female sex, and fewer comorbid conditions.

PMID- 17441295
TI  - Quality control circles: negotiating an efficient work environment.

PMID- 17441296
TI  - Drug expiration dates - meaningful?

PMID- 17441297
TI  - [Respecting the wishes of Mister B].

PMID- 17441298
TI  - Delayed and pseudodelayed visual evoked potentials in optic neuritis compared
      with long time echo-short tau inversion recovery magnetic resonance imaging of
      optic nerve.
AB  - Twenty patients affected by optic neuritis (ON) underwent serial visual evoked
      potential (VEP) recordings, performed with multiple electrode arrays, and with
      stimuli of 1 and 3 cycles per degree (cpd) for 1 year. VEP findings were
      correlated with long time echo-short tau inversion recovery (LTE-STIR) magnetic
      resonance imaging (MRI) of optic nerves and with visual field tests. MRI showed
      lesions in 95.2% of acute ON and in 66.6% of the 1 year follow-up. VEPs were
      classified into really 'delayed' VEPs and 'pseudodelayed' VEPs, based on their
      scalp distribution. Furthermore, VEPs to 1 or 3 cpd could be 'delayed' or
      'pseudodelayed' in the same patient. Real delays could be recorded at onset or
      shortly after ON, and indicated the possibility of recovery of visual functions
      and good functional prognosis. Pseudodelays, to 3 cpd, corresponded to prominent
      central scotomata and indicated poor prognosis for the recovery of visual
      function, unless a breakthrough of normal or delayed components appeared in the
      first 4 months following acute ON. Pseudodelayed VEPs clustered in patients with
      longer demyelinating lesions, as shown by LTE-STIR MRI. There was no correlation
      between latency of VEPs and length of plaques. Our study addresses some
      reconsiderations of the pathophysiology of conduction delay in acute optic
      neuritis.

PMID- 17441299
TI  - Visual evoked potentials elicited by a moving unidimensional noise pattern.
AB  - (1) Motion onset and offset visual evoked potentials (VEPs) were recorded in
      normal human subjects using a unidimensional noise pattern moving at 1, 8 and 64
      degrees/s. The maximum N1-P1 amplitude of the motion onset response was obtained
      when using a fine noise pattern (maximum energy at 5.2 cpd) moving at 8
      degrees/s. (2) At a velocity of 8 degrees/s, the motion onset response (fine
      pattern, 0.70 contrast) showed a morphology similar to the pattern disappearance
      response. Both at a lower (1 degrees/s) and a higher velocity (64 degrees/s) the
      N1-P1 amplitude of the motion onset complex was significantly reduced. The
      latency of the motion onset response (8 degrees/s) and the pattern disappearance
      complex were significantly different. (3) The effect of lowering the spatial
      content of the noise pattern on the amplitude of the motion onset response was
      different for the 3 velocities tested: the largest effect was at the lower
      velocity of 1 degrees/s; there was no similar effect on the pattern disappearance
      response. (4) With decreasing contrast, the N1-P1 amplitude of the motion onset
      response at 8 degrees/s decreased, but this reduction in amplitude was much less
      than that of the disappearance response. The contrast dependency of the motion
      onset complex was identical for binocular and monocular recordings. (5)
      Increasing the motion duration or the duration of the interstimulus interval did
      not alter the general morphology of the motion response.

PMID- 17441300
TI  - Age-related changes in event-related potentials in visual discrimination tasks.
AB  - Visual event-related potentials and reaction times in physical and semantic
      discrimination tasks were studied in 29 normal subjects between the ages of 21
      and 74 years. The NA, N2 and P3 components of the evoked potential, and simple
      and GO/NOGO reaction times were observed in both kinds of discrimination.
      Significant age-related slowing of the GO/NOGO reaction time was observed only in
      the semantic discrimination task. The N2 and P3 latencies elicited by both the
      physical and semantic stimuli were significantly and positively correlated with
      age, although there was no significant correlation between the NA latency and
      age. The interpeak latency between N2 and P3 showed no age-related changes. The
      decline of cognitive information processing with advancing age was evident from
      the classification of a perceived event as reflected by the N2 component.

PMID- 17441301
TI  - Detection of neurological injury using time-frequency analysis of the
      somatosensory evoked potential.
AB  - Somatosensory evoked potentials (SEPs) can be monitored during critical surgery
      to help detect or possibly prevent post-operative injury to the brain. This paper
      presents the application of time-frequency analysis to detect both temporal and
      spectral changes in the SEP waveform that may occur due to injury. Time-frequency
      distributions, which provide a measure of signal energy at both a specific time
      and frequency, were computed for averaged SEPs acquired from anesthetized cats
      during various stages of hypoxic injury and then recovery. Wigner distributions
      of SEP waveforms were found to contain a peak of signal energy at a specific time
      and frequency, a peak that is altered during injury. Four characteristics of the
      distribution peak that demonstrate changes due to injury were computed: peak
      time, peak frequency, peak power, and peak sharpness. Peak time was found to
      increase while peak frequency, peak power, and peak sharpness were found to
      decrease during injury. Furthermore, the total signal power in a time-frequency
      space around the normal peak location was monitored by developing a time
      frequency window filter (TFWF) method. For all cases, onset of hypoxia was
      detected an average of 2.75 min earlier by the TFWF method than by the
      conventional amplitude measurement method. Time-frequency analysis of EP signals
      may therefore be useful as a monitoring tool for early detection of brain injury.

PMID- 17441302
TI  - Detailed analysis of the latencies of median nerve somatosensory evoked potential
      components, 1: selection of the best standard parameters and the establishment of
      normal values.
AB  - In order to objectively select the standard parameters best suited for the
      evaluation of somatosensory conduction in median nerve somatosensory evoked
      potentials (SEP), we performed a detailed statistical analysis of intersubject
      variability for the latencies of SEP components based on the recordings of 62
      normal subjects. Multiple regression analyses for height, age, (age--20)2 and sex
      were performed for the latencies of 13 components and 78 intercomponent
      intervals, and the residual variance was used as an indicator of the stability of
      each parameter. As a result, N9 onset in EPi-NC lead, N11' onset in C6S-Fz lead,
      P13/14 onset in scalp-NC leads, for which N13' onset recorded in C6S-Fz lead may
      substitute, and N20 onset in CPc-Fz lead were the most stable time-points
      selected as standards. N11 onset in C6S-NC, which other authors have recommended
      as the standard point representing spinal entry, was not recorded consistently,
      and P11 onset in scalp-NC leads was also unstable. N20 peak and N13'-N20 interval
      (equivalent to conventional central conduction time) were extremely unstable. We
      presented the nomograms to find normal limits of the standard parameters
      corresponding to the given values of the predictor variables (height, age or
      sex). As the standard recording montage in routine clinical examinations, we
      recommended a simple method using Fz reference, for example (1) EPi-Fz, (2) C6S
      Fz, (3) CPc-Fz, because this montage is sufficient to measure the stable standard
      parameters.

PMID- 17441303
TI  - Postcentral origin of P22: evidence from source reconstruction in a realistically
      shaped head model and from a patient with a postcentral lesion.
AB  - The source of the radial field of P22 was previously attributed either to the
      precentral (area 4) or postcentral (area 1) gyrus, on the basis of interpretation
      of potential maps recorded on the skin or cortex, respectively. The present study
      used dipole localization within realistically shaped head models and constrained
      the inverse solution by using the individual cortex and the normals on it, as
      derived from MR-tomography. In all normal subjects in which a sufficient solution
      was obtained (6 of 10, goodness of fit above 90%, and relative power of above
      94.4% in principal-component analysis) the P22 source resided at the crown of the
      postcentral gyrus. Further evidence came from a patient with a postcentral lesion
      (area 1) and loss of P22, while N20-P20 was preserved.

PMID- 17441304
TI  - Scalp topography and dipolar source modelling of potentials evoked by CO2 laser
      stimulation of the hand.
AB  - CO2 laser evoked potentials to hand stimulation recorded using a scalp 19-channel
      montage in 11 normal subjects consistently showed early N1/P1 dipolar field
      distribution peaking at a mean latency of 159 ms. The N1 negativity was
      distributed in the temporoparietal region contralateral to stimulation and the P1
      positivity in the frontal region. The N1/P1 response was followed by 3 distinct
      components: (1) N2a reaching its maximal amplitude at the vertex and
      ipsilaterally to the stimulated hand, (2) N2b mostly distributed in the frontal
      region, and (3) P2 with a mid-central topography. Brain electrical source
      analysis showed that this sequence was explained, with a residual variance below
      5%, by a model including two dipoles in the upper bank of the Sylvian fissure of
      each hemisphere, a frontal dipole close to the midline, and two anterior medial
      temporal dipoles, thus suggesting a sequential activation of the two second
      somatosensory areas, anterior cingulate gyrus and the amygdalar nuclei or the
      hippocampal formations, respectively. This model fitted well with the scalp field
      topography of grand average responses to stimulation of left and right hand
      obtained across all subjects as well as when applied to individual data. Our
      findings suggest that the second somatosensory area contralateral to the
      stimulation is the first involved in the building of pain-related responses,
      followed by ipsilateral second somatosensory area and limbic areas receiving
      noxious inputs from the periphery.

PMID- 17441305
TI  - Analysis of the middle latency evoked potentials to angular acceleration impulses
      in man.
AB  - The middle latency vestibular evoked potential (ML-VsEP) recorded with scalp
      electrodes in man in response to impulses of angular acceleration is dominated by
      a forehead positive peak at about 15 ms and a negative peak at about 20 ms; the
      peak to peak amplitude of this component is about 30 microV. This is followed by
      slower, smaller amplitude activity. The latency of this initial peak is similar
      to the latency of the vestibulo-ocular reflex (VOR) in monkeys. The present study
      was undertaken to elucidate the possible relation between the ML-VsEPs and VOR.
      This included recordings from forehead-mastoid electrodes (sites used to record
      VsEP) and other scalp electrodes and the recording of potentials due to eye
      movement: the electro-oculogram. Direct recording of eye movements was also
      conducted using an infra-red reflection device in those experiments in which the
      head was not moved. The recordings were conducted in man during vestibular
      stimulation eliciting VsEPs, during voluntary eye movements and during caloric
      and optokinetic stimulation. These experiments indicated that the 15-20 ms
      component of the ML-VsEP was not due to movements of the eye (corneo-retinal
      dipole). The large amplitude 15-20 ms component of the ML-VsEP was similar in
      general magnitude, waveform, polarity, duration and rise time to the highly
      synchronous pre-saccadic spike (neural and/or myogenic) which precedes nystagmus
      and voluntary saccades. It therefore probably represents vestibular-initiated
      electrical activity in motor units of the extra-ocular muscles which then produce
      anti-compensatory saccades.

PMID- 17441306
TI  - A comparison of forepaw and vibrissae somatosensory cortical evoked potentials in
      the rat.
AB  - Somatosensory evoked potentials were elicited in anesthetized rats by electrical
      stimulation of the forepaw (F-SEP) or the vibrissae (V-SEP) and were compared in
      order to study which of these is a more valid animal model for studying the
      physiology and pathophysiology of somatosensory evoked potentials (SEPs) that are
      often recorded in man in a clinical setting. Intensity and rate functions were
      measured for the two potentials. The V-SEPs had larger amplitudes than the F-SEPs
      at high stimulus intensity and low stimulus rate. Furthermore, the ratios of the
      maximal amplitude of the F-SEP to that of the V-SEP (0.66) and of the areas under
      the curves of the two responses (0.75) reflected the smaller representation of
      the forepaw in the primary somatosensory cortex of the rat, compared to the
      vibrissae (ratio of cortical areas about 0.79). The differences should be taken
      into account when using median nerve SEP in the rat as a model of the human SEP.
      Study of V-SEPs in rat may provide insight into trigeminal nerve SEPs in man,
      which are also occasionally used for neurological evaluation.

PMID- 17441307
TI  - Strategies for minimizing 60 Hz pickup during evoked potential recording.
AB  - Electrical interference at mains power supply frequency can adversely affect the
      recording of evoked potentials and can be especially destructive in an operating
      room setting. We investigated 60 Hz interference in electrode cables running from
      subject to preamplifier and further examined methods to eliminate such
      interference. We conclude that braiding electrode wires is highly efficacious in
      such interference reduction, presumably by reducing the magnetic flux enclosed by
      the wires. We further indicate that the use of flexible metal hose fabricated
      from Permalloy 80 may effect further interference reduction.

PMID- 17441308
TI  - Inter-observer variations of digital radiograph pulmonary nodule marking by using
      computer toolkit.
AB  - OBJECTIVE: To assess inter-observer variations of pulmonary nodule marking in
      routine clinical chest digital radiograph (DR) softcopy reading by using a lung
      nodule computer toolkit. METHODS: A total of 601 chest posterior-anterior DR
      images were randomly selected from routine outpatient screening in Peking Union
      Medical College Hospital. Two chest radiologists with experience more than ten
      years were first asked to read the images and mark all suspicious nodules
      independently by using computer toolkit IQQA-Chest, and to indicate the
      likelihood for each nodule detected. They were also asked to draw the boundary of
      the identified nodule manually on an enlarged region of interest, which was
      instantly analyzed by IQQA-Chest. Two sets of diagnostic reports, including the
      marked nodules, likelihood, manually drawn boundaries, quantitative measurements,
      and radiologists' names, were automatically generated and stored by the computer
      system. One week later, the two radiologists read the same images together by
      using the same computer toolkit without referring to their previous reading
      results. Marking procedure was the same except that consensus was reached for
      each suspicious region. Statistical analysis tools provided in the IQQA-Chest
      were used to compare all the three sets of reading results. RESULTS: In the
      independent readings, Reader 1 detected 409 nodules with a mean diameter of 12.4
      mm in 241 patients, and Reader 2 detected 401 nodules with a mean diameter of
      12.6 mm in 253 patients. In the consensus reading, a total of 352 nodules with a
      mean diameter of 12.4 mm were detected in 220 patients. Totally, 42.3% of Reader
      1's and 45.1% of Reader 2's marks were confirmed by the consensus reading. About
      40% of each reader's marks agreed with the other. There were only 130 (14.4%) out
      of the total 904 unique nodules were confirmed by both readers and the consensus
      reading. Moreover, 5.6% (51/904) of the marked regions were rated identical
      likelihood in all three readings. Statistical analysis showed significant
      differences between Readers 1 and 2, and between consensus and Reader 2 in
      determining the likelihood of the marks (P < 0.01), but not between consensus and
      Reader 1. No significant difference in terms of size was observed in nodule
      segmentation between either two of the three readings. CONCLUSION: Large
      variations in nodule marking and nodule-likelihood determination but not in
      nodule size were observed between experts as well as between single-person
      reading and consensus reading.

PMID- 17441309
TI  - Comparison of short- and long-term outcomes between Cypher and TAXUS drug-eluting
      stents for in-stent restenosis.
AB  - OBJECTIVE: To compare the short- and long-term clinical outcomes between
      sirolimus-eluting stent (Cypher stent) and paclitaxel-eluting stent (TAXUS stent)
      in patients with in-stent restenosis (ISR) lesions of the coronary arteries.
      METHODS: From December 2002 to March 2005, 253 patients with ISR lesions of the
      coronary arteries were selected and divided into two groups. Cypher group (152
      cases) was treated with Cypher or Cypher Select stents, and TAXUS group (101
      cases) with TAXUS stents. A total of 262 ISR lesions in these patients were
      treated with 308 drug-eluting stents (DESs), including 176 Cypher or Cypher
      Select stents and 132 TAXUS stents. All patients were followed up for 10 months.
      Procedure success rates of DES implantation in both groups were observed. Major
      adverse cardiac events (MACE) rates in hospital and at 10 months follow-up, as
      well as in-DES restenosis observed using coronary angiography at follow-up were
      compared between two groups. RESULTS: Success rate of DES implantation was 100%
      in both groups. No significant difference in MACE rate during hospitalization was
      found between the two groups. However, at 10 months follow-up, MACE rate was
      higher in TAXUS group than in Cypher group (16.00% vs. 6.67% , P = 0.031). As for
      coronary angiography at 10 months follow-up, we observed an increasing tendency
      of in-DES restenosis rate in TAXUS group compared with Cypher group (29.41% vs.
      14.04%, P = 0.075). CONCLUSIONS: Cypher and TAXUS DESs both have good short- and
      long-term outcomes in treating ISR. Cypher DES proved better long-term clinical
      outcome than TAXUS DES.

PMID- 17441310
TI  - Application value of magnetic resonance sequences in diagnosis of early spinal
      metastatic tumor.
AB  - OBJECTIVE: To investigate the clinical value of different magnetic resonance (MR)
      pulse sequences in diagnosis of spinal metastatic tumor. METHODS: Fifteen
      patients with clinically suspected spinal metastatic tumor were included in this
      study. These patients were with documented primary tumors. Four MR pulse
      sequences, T1-weighted spin echo (T1WI SE), T2-weighted fast spin echo (T2WI
      FSE), short time inversion recovery (STIR), and gradient echo 2-D multi echo data
      imaging combination (GE Me-2D) were used to detect spinal metastasis. RESULTS:
      Fifteen vertebral bodies were entire involvement, 38 vertebral bodies were
      section involvement, and totally 53 vertebral bodies were involved. There were 19
      focal infections in pedicle of vertebral arch, 15 metastases in spinous process
      and transverse process. Fifty-three vertebral bodies were abnormal in T1 WI SE
      and GE Me-2D, 35 vertebral bodies were found abnormal in T2WI FSE, and 50
      vertebral bodies were found abnormal in STIR. The verges of focal signal of
      involved vertebral bodies were comparatively clear in T1WI SE, comparatively
      clear or vague in T2WI FSE, vague in STIR, and clear in GE Me-2D. CONCLUSIONS: GE
      Me-2D may be the most sensitive technique to detect metastases. So three
      sequences (T1WI SE, T2WI FSE, GE Me-2D) can demonstrate the early changes of
      spinal metastasis roundly.

PMID- 17441311
TI  - Ureteral injury during gynecological laparoscopic surgeries: report of twelve
      cases.
AB  - OBJECTIVE: To investigate ureteral injury during gynecological laparoscopic
      surgeries. METHODS: From January 1990 to December 2005, 12 868 gynecological
      laparoscopic surgeries were conducted in Peking Union Medical College Hospital
      with 12 ureteral injuries reported. The present study investigated several
      aspects, including surgical indications, uterine size, pelvic adhesion, operative
      procedures, symptoms, diagnostic time and methods, injury site and type,
      subsequent treatment, and prognosis. RESULTS: The incidence of ureteral injury
      was 0.093% (12/12 868) in all cases, 0.42% (11/2 586) in laparoscopic
      hysterectomy [laparoscopically assisted vaginal hysterectomy (LAVH) or total
      laparoscopic hysterectomy (TLH)], and 0.01% (1/10 282) in non-LAVH surgeries.
      Enlarged uterus, pelvic adhesion, and endometrosis were risk factors associated
      with ureteral injury. Only one injury was found intraoperatively while others
      were found postoperatively. The injury sites were at the pelvic brim (2 cases) or
      the lower part of ureter (10 cases). Patients were treated with ureteral stenting
      (effective in 2 cases) or laparotomy and open repair. Prognoses were favorable in
      most cases. CONCLUSIONS: Most laparoscopic ureteral injuries occur during
      laparoscopic hysterectomy. Further evaluation is required when ureteral injury is
      suspected, and surgical repair is the major treatment for ureteral injury.

PMID- 17441312
TI  - Color Doppler ultrasonography appearances of renal vein thrombosis and its
      diagnostic value.
AB  - OBJECTIVE: To evaluate color Doppler ultrasonography (CDU) appearances of renal
      vein thrombosis (RVT) and its diagnostic value. METHODS: Ten patients with RVT
      were analyzed retrospectively. Renal structure, distributions of intrarenal flow
      signals, echogenicity, and flow fullness in main renal veins were observed with
      CDU. Resistance index (RI) was recorded from the waveforms of segmental or
      interlobar renal artery. RESULTS: Ten kidneys in nine patients were confirmed to
      have thrombus within the main renal veins, and one patient was confirmed to have
      thrombus within the small intrarenal veins. The appearances of the main renal
      vein thrombosis included full of solid echogenicity or strip echogenicity and
      complete or partial filling defect within the main renal veins, and absent or a
      few intrarenal venous flow signals in 70% of kidneys involved. The appearances of
      intrarenal vein thrombosis included obscure renal structure and no venous flow
      signal within the involved part of the kidneys. Reverse diastolic flow in the
      intrarenal artery had only a sensitivity of 36% (4/11); in other 7 kidneys
      without intrarenal arterial reverse diastolic flow, increased RI (mean, 0.84;
      range, 0.74-0.96) was found. CONCLUSION: CDU is helpful for rapid clinical
      diagnosis and follow-up of RVT, and therefore can be the first imaging modality
      of choice for RVT.

PMID- 17441313
TI  - Inhibitory effect of angiotensin II type 1 receptor-associated protein on
      vascular smooth muscle cell growth and neointimal formation.
AB  - OBJECTIVE: To investigate the mechanism of a novel angiotensin II type 1 receptor
      associated protein (ATRAP) interfering with angiotensin II type 1 (AT1) receptor
      mediated vascular smooth muscle cell (VSMC) growth and neointimal formation.
      METHODS: VSMCs isolated from thoracic aorta of adult Sprague-Dawley (SD) rats
      were used in this study. ATRAP cDNA was subcloned into pcDNA3 vector and then
      transfected into VSMCs. DNA synthesis and extracellular signal-regulated kinase
      (ERK) and phospho-ERK expressions in VSMCs were assayed by measurement of 3H
      thymidine incorporation and Western blotting, respectively. Morphological changes
      were observed in the balloon injured artery with or without transfection of ATRAP
      cDNA using 12-week-old male SD rats. RESULTS: ATRAP overexpression in VSMCs
      inhibited angiotensin II (Ang II)-induced 3H thymidine incorporation 48 hours
      after Ang II stimulation (P < 0.05). In VSMC, Ang II stimulation increased the
      phosphorylation of ERK, which reached the peak around 60 minutes. The activation
      of phospho-ERK was significantly decreased by ATRAP (P < 0.05). Neointimal
      formation was markedly inhibited by ATRAP overexpression in injuried arteries.
      CONCLUSIONS: The AT1 receptor-derived activation of ERK plays an essential role
      in Ang II-induced VSMC growth. The growth inhibitory effects of ATRAP might be
      due to interfering with AT1 receptor-mediated activation of ERK in VSMC growth
      and neointimal formation.

PMID- 17441314
TI  - Plasma resistin levels and single-nucleotide polymorphisms in resistin gene 5'
      flanking region in patients with stroke.
AB  - OBJECTIVE: To analyze the role of resistin in insulin resistance (IR) through
      investigating the variation of plasma resistin levels and single-nucleotide
      polymorphisms (SNPs) in resistin gene 5' flanking region in stroke patients.
      METHODS: In 103 atherothrombotic cerebral infarction (ACI) patients, 85 lacunar
      infarction (LI) patients, 70 intracerebral hemorrhage (ICH) patients, and 86
      healthy controls, plasma resistin and insulin levels were measured by ELISA, SNPs
      in resistin gene 5' flanking region were detected by PCR and direct DNA
      sequencing. The subjects' body height and weight, the body mass index,
      quantitative insulin sensitivity check index (QUICKI), blood pressure, and the
      concentration of fasting plasma glucose, triglyceride, total cholesterol,
      creatinine, low-density lipoprotein, and high-density lipoprotein were also
      determined. RESULTS: QUICKI was significantly lower in the ACI and ICH patients
      (0.316 +/- 0.037 and 0.309 +/- 0.032, respectively) than that in the controls
      (0.342 +/- 0.043, P < 0.001), while plasma resistin level was significantly
      higher in the ACI and ICH patients (6.36 +/- 3.79 and 7.15 +/- 4.27 ng/mL,
      respectively) than that in the controls (5.28 +/- 2.56 ng/mL, P < 0.05), but such
      difference was not observed in the LI patients compared with controls. There was
      a statistically negative correlation between plasma resistin level with QUICKI (r
      = -0.228, P < 0.001). The distributions of allele and genotype frequencies of
      resistin gene - 420C > G and - 537A > C SNPs were not significantly different
      among the different groups, and those SNPs were not correlated with other
      clinical and biochemical parameters. CONCLUSIONS: Plasma resistin is associated
      with stroke by participating in the development of IR. The SNPs in resistin gene
      5' flanking region has no impact on the plasma resistin level.

PMID- 17441315
TI  - Rna interference of annexin II gene in PC3 cells by using small interference RNA
      synthesized with in vitro transcription.
AB  - OBJECTIVE: To silence annexin II gene expression by using small interference RNA
      (siRNA) in prostate cancer cell line PC3. METHODS: For in vitro transcription,
      four sequences of 29-nucleotide DNA template oligonucleotides were designed, and
      one pair of the sequences were complementary to annexin II gene. The other pair
      was negative control. The 8 nucleotides at the 3' end of each oligonucleotide
      were complementary to the T7 Promoter Primer. The sense and antisense siRNA
      templates were transcribed by T7 RNA polymerase and the resulting RNA transcripts
      were hybridized to create dsRNA. The siRNA was transfected into prostate cancer
      cell PC3. For assaying the efficiency of siRNA, confocal microscopy, Northern
      blotting, and Western blotting were employed to examine the expression of annexin
      II protein and its mRNA. 3H thymidine was used to measure DNA synthesis. RESULTS:
      The siRNA sequence specific to annexin II gene was capable of inhibiting the
      expression of annexin II protein and its mRNA. And cellular DNA synthesis was
      significantly reduced in siRNA transfected cells. CONCLUSIONS: The protocol for
      the synthesis of siRNA by T7 RNA polymerase is feasible. Annexin II might be
      involved in DNA synthesis.

PMID- 17441316
TI  - Combination of gamma-interferon with TRAIL and cisplatin or etoposide induces
      apoptosis in human neuroblastoma cell line SH-SY5Y.
AB  - OBJECTIVE: To study the effect of gamma-interferon (IFNgamma), tumor necrosis
      factor related apoptosis inducing ligand (TRAIL), and cisplatin or etoposide
      induced apoptosis in human neuroblastoma cell line SH-SY5Y and its possible
      molecular mechanisms. METHODS: The expressions of Caspase 8 mRNA and protein were
      detected with RT-PCR and Western blot analysis. The effects of IFN-gamma, TRAIL,
      IFNgamma + TRAIL, IFN-gamma + Caspase 8 inhibitor + TRAIL, IFNgamma + cisplatin +
      TRAIL, and IFNgamma + etoposide + TRAIL on the growth and apoptosis of SH-SY5Y
      cells were detected with the methods of MTT and flow cytometry. The relative
      Caspase 8 activity was measured with colorimetric assay. RESULTS: Caspase 8 was
      undetectable in SH-SY5Y cells but an increased expression of Caspase 8 mRNA and
      protein was found after treatment with IFNgamma. SH-SY5Y cells themselves were
      not sensitive to TRAIL, but those expressing Caspase 8 after treatment with
      IFNgamma were. The killing effect of TRAIL on SH-SY5Y cells expressing Caspase 8
      was depressed by Caspase 8 inhibitor. Cisplatin and etoposide could enhance the
      sensitivity of TRAIL on SH-SY5Y cells. The relative Caspase 8 activity of SH-SY5Y
      cells in IFN-gamma + TRAIL group was significantly higher than those of control
      group, IFN-gamma group, TRAIL group, and inhibitor group (P < 0.01). There was no
      significant difference among IFN-gamma + TRAIL group, IFNgamma + cisplatin +
      TRAIL group, and IFNgamma + etoposide + TRAIL group. CONCLUSIONS: IFNgamma could
      sensitize SH-SY5Y cells to TRAIL-induced apoptosis and this may be realized by
      the up-regulation of Caspase 8. Cisplatin and etoposide could enhance the killing
      effect of TRAIL on SH-SY5Y cells.

PMID- 17441317
TI  - Role of Caspase-3 in acute light damage to retina of rats.
AB  - OBJECTIVE: To investigate the role of Caspase-3 in retinal damage caused by light
      exposure in rats. METHODS: Light injury to retina was induced by persistent
      exposure to illumination (intensity: 30 000 +/- 50 lux) of operating microscope
      for 30 minutes in the right eyes of Sprague-Dawley rats. The pathological changes
      of retina were observed under optical and electron microscopies at different time
      points, which were 6 hours, 1, 3, 7, and 15 days after the light exposure.
      Apoptosis of retinal cells was analyzed by flow cytometry. The activity of
      Caspase-3 was evaluated by using the Caspase-3 assay kit. At the same time, the
      expression of Caspase-3 protease was determined with Western blot analysis.
      RESULTS: The examination results of optical and transmission electron microscopes
      showed that edema of inner and outer segments of the retina, especially the
      chondriosome inside the inner segment, became obvious 6 hours after the light
      exposure. The change was deteriorated along with the increasing time. The
      structures of the discoidal valve dissociated in the outer segment
      simultaneously. Disorderly arranged nuclei, karyopycnosis, and thinning in the
      outer nuclear layer were observed. The retinal pigment epithelium almost
      disappeared during the later stage. The staining results of Annexin-V combined
      with PI demonstrated that the proportion of apoptotic cells increased with time.
      The proportion between 7th day (82.7%) and 15th day (80.4%), however, showed no
      significant difference. Caspase-3 became remarkably active with the lapse of
      time, which increased from 0.02 at 6th hour to the peak of 9.8 at 7th day before
      it started to descend. The Western blot detected a expression of the active form
      of Caspase-3 at 7th day and 15th day. CONCLUSION: Apoptosis of photoreceptor
      cells is markedly involved in the light damage and Caspase-3 protease may play an
      important role in the apoptotic process of the retina after light exposure in
      rats.

PMID- 17441318
TI  - Involvement of p38 mitogen-activated protein kinase in E. coli-induced U937
      apoptosis.
AB  - OBJECTIVE: To investigate whether the effect of E. coli on U937 cell lines
      apoptosis is mediated via p38 mitogen-activated protein kinase (MAPK) activation.
      METHODS: The U937 cell lines were treated with E. coli at different time or
      together with SB203580, an inhibitor for p38. Cell apoptosis was analyzed by flow
      cytometry. p38 activities were detected by Western blotting. RESULTS: E. coli
      induced apoptosis in cultured U937 cell lines in a time-dependent manner. The
      phosphorylation of p38 was induced after 10 minutes infection, reached the peak
      after 20 minutes, and started to decline after 30 minutes. In contrast, the level
      of total p38 protein was not changed in whole experimental period. Inhibition of
      p38 with SB203580 significantly inhibited E. coli induced apoptosis in U937
      cells. CONCLUSION: The activation of the p38 MAPK in U937 cell lines by E. coli
      is a major pathway to mediate the apoptosis.

PMID- 17441319
TI  - Solid cystic papillary tumor of pancreas in eight children.
AB  - OBJECTIVE: To estimate the clinical and pathological features of pancreatic solid
      cystic papillary tumor (SCPT) in children. METHODS: From 2000 to 2005, 8 cases
      with SCPT of the pancreas were analyzed retrospectively. All cases but one were
      females. Average age was 12.8 years. By case review, we discussed the clinical
      and pathological features of SCPT in children. RESULTS: The chief complains were
      abdominal pain and palpable mass. There were 3 cases in the head, 1 case in the
      body, and 4 cases in the tail of pancreas. The procedures employed included local
      resection (1 case), distal pancreatectomy (5 cases), pancreaticoduodenectomy (1
      case), and biopsy (1 case). Histological examination showed solid with cystic
      areas and papillary protrusions in the 8 cases; as for immunohistochemical
      examinations, the positive rate was 100% for alpha-antitrypsin (AACT), 87.5% for
      vinmentin, and 62.5% for neuron-specific enolase (NSE). The patients were
      followed up for 2 months to 4 years but one was lost by follow-up and all were
      alive postoperatively. SCPT in 2 cases relapsed. CONCLUSION: Occurring
      predominantly in young females, SCPT is usually curable by surgical resection
      with a favorable prognosis.

PMID- 17441320
TI  - Functional and structural recovery of injured spinal cord following delayed X
      irradiation in rats.
AB  - OBJECTIVE: To test the hypothesis that delayed X-irradiation can enhance the
      functional and structural recovery of the injured spinal cord in rats. METHODS:
      Seventy Sprague-Dawley rats were randomly divided into two groups, 35 rats in
      each. The control group sustained a one-minute clip compression (force of clip
      was 30 g) injury of the spinal cord at the T2 level, without X-irradiation. The
      experimental group received X-irradiation 14 days after injury. Neurological
      function was assessed by the modified Tarlov method, including hind limbs
      movement, inclined plane, and pain withdrawal. These tests were performed in a
      blinded fashion at 3, 7, 14, 21, 28, 35, and 42 days after injury. At 43 days
      after injury, histological examination of the injured spinal cord was performed
      following decapitation of the rats. RESULTS: Sixty-two rats met the experimental
      requirements (spinal cord injury was similar), 32 rats in experimental group and
      30 rats in control group. Statistically significant difference was observed
      between the two groups in hind limbs movement and inclined plane (P < 0.01), but
      not in the pain withdrawal test. The edema and necrosis areas of injured spinal
      cords in experimental group were less than those in control group, and axons in
      experimental group were significantly more than those in control group (P <
      0.01). CONCLUSION: Delayed X-irradiation following spinal cord injury may enhance
      functional recovery by improving and restoring structural integrity of the
      injured spinal cord in rats.

PMID- 17441321
TI  - Anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high
      altitude exposure.
AB  - OBJECTIVE: To investigate the anti-hypoxia and anti-oxidation effects of
      aminophylline on human with acute high-altitude exposure. METHODS: Totally 100
      young male army members newly recruited from Sichuan province (400 meters above
      sea level) were enrolled. They were randomly divided into two groups: 50 in
      aminophylline group (A group) and 50 in control group (C group). A group and C
      group orally took aminophylline and placebo respectively for 10 days, 7 days
      before entering Lhasa (3 658 meters above sea level) by air and 3 days after it.
      Several parameters were measured at three time points: before drug taken, 7 days
      after drug taken, and 3 days after ascending high altitude. These parameters
      included serum levels of nitric oxide (NO), superoxide dismutase (SOD), catalase
      (CAT), hydrogen dioxide (H2O2), lactic acid (LA), as well as arterial oxygen
      saturation (SO2), arterial oxygen partial pressure (PaO2), and arterial carbon
      dioxide partial pressure (PaCO2). Statistical analysis was conducted to compare
      the difference between two groups with Stata 7.0 software system. RESULTS: There
      were no statistical differences between groups in hypoxia and oxidation
      indicators before and after drug taken in plain area. Three days after ascending
      high altitude, the serum levels of SOD, CAT, H2O2, LA, PaCO2 increased in both
      groups, yet to a much larger degree in C group than A group (P < 0.01); and NO,
      SO2, PaO2 decreased more markedly in C group (P < 0.05 for NO, P < 0.0001 for SO2
      and PaO2). CONCLUSION: Aminophylline has significant anti-hypoxia and anti
      oxidation effects at high altitude.

PMID- 17441322
TI  - Successful resection of cardiac angiosarcoma combined with right coronary artery
      bypass grafting.

PMID- 17441323
TI  - Mediastinal cavernous hemangioma: report of one case.

PMID- 17441324
TI  - [Construction of shRNA expression vectors for autophagy gene Beclin 1 and effect
      of the vectors on transfected HeLa cells in vitro].
AB  - OBJECTIVE: Autophagy gene Beclin 1 plays an important role in several types of
      human cancer. In this study, RNA interference (RNAi) technique was employed to
      determine the effect of inhibiting Beclin 1 on the growth of tumor cells.
      METHODS: According to the encoding sequence of mRNA of Beclin 1, the target site
      for the RNAi technique was designed and the vector for shRNA (short hairpin RNA)
      expression in tumor cells was constructed. The HeLa cell line was transfected
      with the sfRNA to inhibit the expression of Beclin 1. RESULTS: The constructed
      vector significantly inhibited the expression of the mRNA and protein of Beclin 1
      in the HeLa cells. The growth of the transfected cells was promoted, and less
      apoptosis cells were identified in these cells. CONCLUSIONS: The shRNA expression
      vector can effectively inhibit the expression of Beclin 1 in the HeLa cells, and
      promote the growth of HeLa cells.

PMID- 17441325
TI  - [Construction and screen of recombinant BCG strain expressing and secreting human
      interleukin 12 protein].
AB  - OBJECTIVE: To screen and construct the recombinant Bacillus Calmette-Guerin
      (rBCG) strain expressing and secreting the human interleukin 12 (rBCG-12).
      METHODS: IL-12 complete gene including p40 and p35 subunits was amplified by PCR
      from a plasmid pORF-h IL-12 and cloned into E. coli-Mycobacteria shuttle vector
      pMV361. The recombinant vector was named as rpMV-IL-12. rpMV-IL-12 was confirmed
      by DNA sequencing, and then rpMV-IL-12 was used, by electroporation way, to
      transform the BCG for getting the recombinant rBCG-12 strain. The positive rBCG
      12 clone was screened and identified by kanamycin resistance and IL-12 target
      gene PCR amplification. The IL-12 protein expression of rBCG-12 was induced with
      heat shock reaction. Then rBCG-12 culture supernatant and bacterial precipitation
      were collected respectively and analyzed with SDS-PAGE electrophoresis for their
      protein components. RESULTS: The recombinant shuttle plasmid rpMV-IL-12 was
      constructed successfully. The sequence of amplified IL-12 gene was consistent
      with GenBank report. By SDS-PAGE electrophoresis, it was confirmed that the IL-12
      protein could express and secrete into the supernatant of rBCG-12 strain culture.
      CONCLUSION: The recombinant BCG strain expressing human IL-12 protein, rBCG-12
      strain, is constructed and screened successfully. It is the foundation for
      further research on rBCG-12 immune function.

PMID- 17441326
TI  - [Protein-protein interaction between hypothetical protein Rv1246c and Rv1247c of
      Mycobacterium tuberculosis].
AB  - OBJECTIVE: To investigate the protein-protein interaction between hypothetical
      protein Rv1246c and Rv1247c of Mycobacterium tuberculosis. METHODS: By PCR
      technique, the complete open-reading frame sequences of Rv1246c and Rv1247c gene
      were amplified from the M. tuberculosis H37Rv genomic DNA as template. The PCR
      amplified cDNAs of Rv1247c and Rv1246c gene were subcloned into pGBKT7 and pGADT7
      Rec vector respectively for constructing recombinant plasmids pGBKT7-Rv1247c and
      pGADT7-Rv1246c. After verified by restriction endonuclease digestion and DNA
      sequence determination, the recombinant vectors were used to transform the yeast
      cell AH109 by lithium acetate method. RESULTS: The yeast cells co-transformed
      with pGBKT7-Rv1247c and pGADT7-Rv1246c grew on SD/-Ade/-His/-Leu/-Trp plates, and
      the beta-galactosidase activity assays showed the positive signal. CONCLUSION:
      The hypothetical protein Rv1246c and Rv1247c could interact with each other in
      yeast cells.

PMID- 17441327
TI  - [Cloning and prokaryotic expression of flagellum subunit gene (flaA) of
      Legionella pneumophila].
AB  - OBJECTIVE: To construct the fused expression vector of flaA gene of Legionella
      pneumophila and realize the flaA gene expressing in E. coli so as to set the
      basis for future research on the disease-causing role and immune protective
      response of flaA. METHODS: In this study, the flaA gene, an flagellum subunit
      gene (flaA) of Legionella pneumophila, was obtained from DNA of Legionella
      pneumophila by polymerase chain reaction (PCR), and was harbored into prokaryote
      expression vector, pET32a (+) containing thioredoxin gene Trx. The recombinant
      plasmid (pET-flaA) was analyzed with restriction-endonuclease digestion, PCR and
      DNA sequencing analysis, and transferred into E. coli strain BL21 (DE3) for
      transformation. The expression of fusion protein Trx-flaA was induced with
      isopropy-beta-D-thiogalactoside (IPTG) and examined with SDS-PAGE and Western
      blot techniques. RESULTS: The restriction endonuclease digestion, PCR
      amplification and DNA sequencing analysis showed that the flaA gene of 1435 bp
      was amplified from Legionella pneumophila DNA,and the recombinant plasmid pET
      flaA was constructed successfully. The Trx-flaA protein was expressing in E. coli
      and could be detected with SDS-PAGE and Western blot techniques. CONCLUSION: The
      flaA gene of Legionella pneumophila has highly expressed in prokaryotic cell in
      fused form with Trx.

PMID- 17441328
TI  - [The construction and expression of eukaryotic expression plasmid of Legionella
      pneumophila immunogenic protein].
AB  - OBJECTIVE: To construct the recombinant plasmid of Legionella pneumophila
      immunogenic protein gene (ip) and detect the immunoprotein expression in NIH3T3
      cells. METHODS: The immunogenic protein gene was amplified from DNA of Legionella
      pneumophila by polymerase chain reaction (PCR), then inserted into pcDNA3. 1 (+)
      vector. The recombinant plasmid was named as pcDNA3. 1-ip and analyzed with
      restriction-endonuclease Hind III and BamH I digestion, PCR and DNA sequencing
      techniques. The NIH3T3 cell was transfected by recombinant plasmid pcDNA3. 1-ip
      with lipofection strategy. The transient and stable expression products of
      immunogenic protein gene were detected by immunofluorescence and Western blot.
      RESULTS: We have successfully constructed the recombinant plasmid of Legionella
      pneumophila immunogenic protein gene. It was found that there was dark green
      fluorescence on the cell membrane and inside the cell. Our results showed that
      NIH3T3 cell was transfected by pcDNA3. 1-ip successfully. The rabbit serum
      antibody of Legionella pneumophila detected the NIH3T3 cell transfected stably by
      pcDNA3. 1-ip to express the immunogenic protein with the relative molecular mass
      29 X 1093). CONCLUSION: We have successfully expressed immunogenic protein of
      Legionella pneumophila. The expressed product showed the good immunogenicity and
      immunoreactivity.

PMID- 17441329
TI  - [Experiment research on the location of DNA lesion in the nucleic acid sequence].
AB  - OBJECTIVE: To research on establishing a method that can detect the DNA lesion at
      the level of nucleic acid. METHODS: The TK6 cell was cultured and treated, the
      genomic DNA was extracted, and the strand cleavage was induced by the
      endonuclease Hinf I. Then the genomic DNA was amplified by randomized terminal
      linker-dependent PCR (RDPCR), and hybridized by Southern hybridization with the
      single-stranded probes of the exon 2 of k-ras gene. The PCR products were
      sequenced. RESULTS: The clear hybridized band from the products of RDPCR was seen
      at the expectant position cut by Hinf I. The sequencing analysis showed that the
      position of DNA lesion linked by the linker was just the restriction site of Hinf
      I. CONCLUSION: It can be used to detect the DNA lesion at the level of nucleic
      acid sequence with the combination of sequence and RDPCR technologies.

PMID- 17441330
TI  - [Anti-tumor effect of adenovirus vector generated from homologous recombination
      of bacteria mediating TK gene on hepatic neoplasm cell].
AB  - OBJECTIVE: To test the anti-tumor effect of adenovirus vector generated from the
      homologous recombination of bacteria mediating TK gene on hepatic neoplasm cell.
      METHODS: TK gene was liberated from plasmid and subcloned into shuttle plasmid,
      which formed the plasmid of pAdTrack-GFP-TK. The pAdTrack-GFP-TK plasmid was then
      linealized with Pme I and cotransformed into BJ5183 bacterial cells with
      adenovirus genomic DNA plasmid of pAdEasy-1. The recombinant adenovirus plasmid
      DNA was digested with Pac I and transfected to the 293 cells to package the
      recombinant adenovirus particles. The infection rate of the recombinant
      adenovirus, the target gene expression in the carcinoma cells, the survival rate
      of the GCV treated hepatic neoplasm cell SMMC-7721 infected with recombinant
      adenovirus, and the bystander effect were measured. RESULTS: The titre of
      purified Ad was 2 x 10(12) efu/mL. More than 90% of the SMMC-7721 cells were
      infected when the MOI reached 100. Target gene expression was detected in the
      infected cells. The SMMC-7721 cells infected with AdEasy-GFP-TK were very
      sensitive to the prodrug GCV, with IC50 less than 0.2 pmol/L. Significant
      bystander effect was observed. CONCLUSION: The constructed AdEasy-GFP-TK virus
      can efficiently infect the hepatic neoplasm cells and enable the SMMC-7721 cells
      to express the HSV-TK genes. The bystander effect has improved the anti-tumor
      effect of the TK gene, which makes the clinical application possible.

PMID- 17441331
TI  - [Research on A23187 inducing HL-60 cells to differentiate into dendritic cells].
AB  - OBJECTIVE: To investigate the method for calcium mobilization inducing rapidly to
      produce the dendritic cells (DC) from myeloid leukemia cells. METHODS: HL-60
      cells were cultured with calcium ionophore A23187 (45-720 ng/mL) or plus rhIFN
      gamma (1000 U/mL) for 20-96 hours. The morphologic features of cells were
      observed under inverted microscope and scanning electron microscope, when the
      cell phenotypes of HL-60 treated with A23187 were determined by flow cytometry.
      The proliferation of allogeneic human T cells was tested by mixed lymphocyte
      reaction (Allo-MLR). RESULTS: After treated with A23187 (180 ng/mL) or plus rhIFN
      gamma (1000 U/mL) for 20 hours, some of HL-60 cells were found to have the
      dendritic appearance on cell surface; and the CD83 as a characteristic marker of
      mature DCs, co-stimulating molecules CD80 and CD86 got an up-regulated
      expression. When HL-60 cells were cultured with A23187 for 48 hours, the
      expression of CD83 began going down. A large number of cells with typical
      dendritic appearance were observed after cultured with A23187 for 72 hours, and
      the expressions of CD80 and CD86 were up-regulated continuously. Allo-MLR
      revealed that DCs derived from HL-60 cells treated with A23187 or plus rhIFN
      gamma could stimulate the proliferation of allogeneic human T cells. CONCLUSION:
      The calcium ionophore A23187 can induce the HL-60 cells into mature DCs. This
      study suggests that calcium mobilization for cell differentiation may be an
      alternative way to rapidly acquire DCs.

PMID- 17441332
TI  - [1,25 (OH), dihydroxyvitamin D3 induces the formation of osteoclasts from
      mononuclear cells of rat marrow].
AB  - OBJECTIVE: To investigate the effect of 1,25 (OH)2 dihydroxyvitamin D3 on the
      generation of osteoclasts from mononuclear cells of adult rats. METHODS: With
      density gradient centrifugation, the mononuclear cells were isolated from rat
      bone marrow and cultured in the alpha-MEM with 10(-8) mol/L 1,25 (OH)2
      dihydroxyvitamin D3. The induced cells were fixed and stained with tartrate
      resistant acid phosphatase (TRAP). The bone resorption pits were examined by
      scanning electron microscope, and the morphology of osteoclasts were examined
      with inverted phase contrast microscope. RESULTS: The TRAP+ multinucleated cells
      could be observed on the seventh culturing day of mononuclear cell group. The
      number of TRAP+ multinucleated cells went up to a peak on the fourteenth
      culturing day, and then began to decrease on the twenty-first culturing day. The
      number of osteoclasts induced from mononuclear cell group was more than that from
      bone marrow group (P < 0.05) when it was during the fourteenth culturing day to
      the twenty-third culturing day. The number of bone resorption pits in the
      mononuclear cell group was much more than that in the bone marrow group (P <
      0.05) when it was in period from the tenth culturing day to the twenty-third
      culturing day. The number of osteoclasts induced from mononuclear cell group
      could keep the peak value of lasting 7 days, but that induced from bone marrow
      group could only last its peak value for 3 days. CONCLUSION: The method with
      1,25(OH)2 dihydroxyvitamin D3 inducing the formation of osteoclasts from the
      marrow mononuclear cells is better than that from the whole bone marrow.

PMID- 17441333
TI  - [Combinatorial effects of ST6Gal I siRNA and antisense oligonucleotide-mediated
      gene silence on metastasis ability of cervical carcinoma cells].
AB  - OBJECTIVE: To study the combinatorial effects of small interfering RNA (siRNA)
      and antisense oligonucleotides (ASOs) targeting alpha 2,6 sialyltransferase
      (ST6Gal I) on the cell adhesion and invasiveness of human cervical carcinoma cell
      line, HeLa with over-expressing ST6Gal I. METHODS: The siRNA and ASOs targeting
      to ST6Gal I were designed and synthesized chemically, and then with lipofectamine
      2000, transferred into HeLa cells, which were cultured and divided into 7 groups:
      blank control group, liposome group, siRNA group transfected with ST6Gal I siRNA,
      ASO1 group transfected with ST6Gal I ASO whose target site is same as siRNA, ASO2
      group transfected with ST6Gal I ASO whose target site is different with siRNA,
      siRNA+ASO1 group transfected with siRNA and its homologous ASO1, siRNA+ASO2 group
      transfected with siRNA and its nonhomologous ASO2. RT-PCR was used to examine the
      ST6Gal I mRNA expression. Flow cytometry was used to examine the amount of
      alpha2, 6-sialylation on the HeLa cell surface. The HeLa cell adhesion or
      invasiveness to extracellular matrix (ECM) was analyzed by using CytoMatrix kit
      or cell invasion assay kit, respectively. RESULTS: The expression of ST6Gal I
      mRNA, the amount of a2,6-sialylation of cell surface, the cell adhesion and
      invasion to ECM were remarkably decreased in siRNA group, ASO1 group, ASO2 group,
      siRNA+ASO, group and siRNA+ASO2 group, and all significantly lower than those in
      the blank control group and liposome group (all P < 0.05), especially in
      siRNA+ASO2 group. The difference was significant between siRNA+ASO2 group and
      siRNA group (all P < 0.05). No significant difference was observed between
      siRNA+ASO1 group and siRNA group, neither between blank control group and
      liposome group (all P > 0.05). CONCLUSION: The synthesized chemically specific
      siRNA targeting to ST6Gal I can effectively downregulate the ST6Gal I expression
      in HeLa cell and further lead to the decline of cell adhesion and invasiveness to
      ECM, and use of associating siRNA with ASO targeting to same gene but different
      oligonucleotide location possesses the synergy and additive effect on targeted
      gene expression knocked down.

PMID- 17441334
TI  - [Steady expression and activity determination of recombinant signal peptide of
      mBD2 in SiHa cell].
AB  - OBJECTIVE: To observe the expression pattern and effect of recombinant murine
      beta defensin 2 (rmBD2) on the proliferation of cell transfected with pcDNA3. 1
      (+)/rmBD2. METHODS: The recombinant plasmid pcDNA3. 1 (+)/rmBD2 was transferred
      into SiHa cells. The transfected SiHa cells were selected by G418 with 100
      microg/mL for over 20 days. The steady expressions of rmBD2 protein and rmBD2
      mRNA were detected by immunofluorescence and RT-PCR. The effects of rmBD2 on SiHa
      cell growth and reproduction were measured by MTT. RESULTS: The SiHa cells which
      could stably express the rmBD2 protein were harvested with 100 microg/mL of G418.
      The rmBD2 protein expression was, by immunofluorescence, confirmed and its mRNA
      in SiHa with rmBD2 could be detected at 4 weeks, 6 weeks, 8 weeks, and 10 weeks
      after cell transfected. A 220 bp segment encoding rmBD2 was amplified by RT-PCR
      and proved by sequencing. The SiHa/K cells transfected pcDNA3. 1 (+) and SiHa had
      no expression of rmBD2 protein. The SiHa with rmBD2 expression grew slowly than
      SiHa/K and SiHa control (P < 0.05). CONCLUSION: The screening for SiHa with rmBD2
      expressing stably is successful. The cell growth curve shows that rmBD2 can
      inhibit the proliferation of tumor cells. The above results establish a solid
      foundation for further studying the biological properties and the anti-tumor
      mechanism of beta defensins.

PMID- 17441335
TI  - [Effect of transfected Rv0901 gene on the activity of mice macrophages].
AB  - OBJECTIVE: To test the effect of Rv0901 gene of Mycobacterium tuberculosis on the
      activity of mice macrophages. METHODS: Peritoneal macrophages of mice were
      isolated and transfected with pcDNA3. 1 or pcDNA3. 1-Rv0901 plasmid DNA, along
      with the GFP DNA. The effectiveness of the transfection was detected by RT-PCR.
      The expression of the GFP and the apoptosis ratio of the macrophages were
      detected by FCM 72 hours after the transfection. The level of nitric oxide and
      IFN-gamma in cultural supernatant were also measured 72 hours after transfection.
      RESULTS: All of the macrophages being transfected had the expression of GFP.
      After being transfected with pcDNA3. 1-Rv0901, the 528 bp gene of Rv0901 was
      amplified by RT-PCR. The macrophages transfected with pcDNA3. 1-Rv0901 had higher
      apoptosis ratio [(56.4 +/- 2.0)% vs (19.9 +/- 1.5)%] and released more nitric
      oxide [(40.4 +/- 3.0) micromol/L vs (27.5 +/- 3.2) micromol/L] and IFN-gamma
      [(2.11 +/- 0.031) ng/mL vs (0.62 +/- 0.025) ng/mL] in the cultural supernatants
      than those transfected with pcDNA3. 1 (P < 0.05). CONCLUSION: Transient
      transfection of pcDNA3. 1-Rv0901 increases the apoptosis ratio of the
      macrophages, which could increase the release of nitric oxide and IFN-gamma.

PMID- 17441336
TI  - [Regulatory effect of IkappaBalpha on NF-kappaB activity during viral gene
      transactivation in patients with steroid responsive simple nephrotic syndrome].
AB  - OBJECTIVE: To investigate the expression of inhibitory kappa B alpha
      (IkappaBalpha) and it's regulatory effect on nuclear factor kappa B (NF-kappaB)
      during viral gene transactivation triggered by respiratory tract viruses in
      steroid responsive simple nephrotic syndrome (SRSNS). METHODS: Children with
      SRSNS (including at active and remissive stage) were examined for this research
      project, and healthy children were chosen as controls. TaqMan reverse
      transcription-PCR (RT-PCR), Western blot, electro-mobility shift assays were
      performed to study the protein expression of IkappaBalpha gene and the activity
      of NF-kappaB in peripheral blood mononuclear cells (PBMCs). Simultaneously, RT
      PCR was used to detect the gene expression of respiratory tract viruses
      (including respiratory syncytial virus and influenza virus), and viral antibody
      was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Comparing
      with that from SRSNS at remissive stage and healthy children, the activity of NF
      kappaB from SRSNS at active stage was much higher statistically (P < 0.05). The
      positive correlation between NF-kappaB activation and the gene expression of
      respiratory tract viruses was observed (OR = 27, Kappa coefficient = 0.59, P <0.
      05). In addition, levels of IkappaBalpha protein from children with SRSNS at
      active stage were much lower than those from healthy children and those from
      children with SRSNS at remissive stage (P < 0.05). There was a linear negative
      correlation between the activity of NF-kappaB and the protein level of
      IkappaBalpha (r = -0.884, P < 0.05). On the other hand, levels of IkappaBalpha
      mRNA from SRSNS at active stage were much higher than those from healthy
      children, but much lower than those from children with SRSNS at remissive stage
      (P < 0.05). CONCLUSION: Abnormal expression of IkappaBalpha, which is attributed
      to regulate activity of NF-kappaB, occurs during viral gene transactivation
      triggered by respiratory tract viruses in SRSNS.

PMID- 17441337
TI  - [Hepatitis B virus surface antigen presenting function of peripheral blood
      dendritic cells from liver transplant receipients].
AB  - OBJECTIVE: To test the hepatitis B virus (HBV) antigen presenting capacity of
      peripheral blood dendritic cells (DCs) from liver transplant recipients who were
      in the condition of postoperative HBV clinical clearance. METHODS: Blood samples
      were obtained from 18 postoperative liver transplant recipients and 6 healthy
      adults. The peripheral blood mononuclear cells (PBMC) were isolated and cultured
      in vitro. The DCs were induced by recombainant human interleckin-4 (rhIL-4) and
      recombainant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)
      and collected on day 7 of the culture. The DCs were then incubated with hepatitis
      B virus surface antigen (HBsAg) for 3 hours, and cocultured with allogeneic PBMC
      for 5 days. The 3HTdR was added with 1microci per well 18 hours before the end of
      the culture. The cpm values were identified for all of the cells. RESULTS: Under
      the same culture condition, the proliferation of the cells from the liver
      transplant recipients was poorer than those from the healthy adults (cpm value
      4310.8 +/- 1820.3 vs 19002.5 +/- 13357.8, P < 0.001). The capacity of antigen
      presenting of DCs from the liver transplant recipients was significantly weaker
      than those from the healthy adults (cpm value 4974.9 +/- 2414.7 vs 39258.4 +/-
      5554.9, P < 0.001). CONCLUSION: Antigen presenting capacity of DCs from liver
      transplant recipients, who are in the condition of postoperative HBV clinical
      clearance, is weakened. It might be the reason of the deficient immune response
      to HBV and hepatitis B vaccine of patients with liver transplant. The antigen
      presenting function is associated with the preoperative HBV replication, length
      after operation, prophylaxis of HBV re-infection/HB recurrence, and postoperative
      PBMV HBV DNA.

PMID- 17441338
TI  - [Expression and involved signal transduction pathway of autophagy gene Beclin 1
      in epithelial ovarian cancer].
AB  - OBJECTIVE: To investigate the relationship between the autophagy gene Beclin 1
      involving the PI3K/PKB signaling pathway and the occurrence, development of
      epithelial ovarian carcinoma. METHODS: The expression of Beclin 1, Class I PI3K
      (p110alpha), Class III PI3K (hvps34) or p-PKB was, by immunohistochemistry,
      detected respectively in 25 normal ovarian tissues, 25 benign neoplasia tissues,
      19 borderline tissues, and 69 epithelial ovarian carcinoma tissues. RESULTS: The
      higher expressions of Beclin 1 and hvps34 were found in normal and benign ovarian
      neoplasia tissues; the expressions were reduced in the borderline lesion tissue;
      and the lowest level of expressions could be detected in the ovarian carcinoma
      tissue (P < 0.05). The expressions of p110alpha and p-PKB increased slightly in
      borderline ovarian tissue, and were higher in the epithelial ovarian carcinoma
      tissue than other three groups (P < 0.05). Beclin 1 expressions in the epithelial
      ovarian cancer tissues with stage I - II, high-middle grade differentiation and
      negative lymph node metastasis were higher than those with stage III - IV, low
      grade differentiation and positive lymph node metastasis, but the expressions of
      p110alpha and p-PKB in were lower (P < 0.05). CONCLUSION: Beclin 1 expression is
      down-regulated in epithelial ovarian cancer tissue while the p110alpha, hvps34
      and p-PKB are having the abnormal expressions on PI3K/PKB signaling pathway,
      which may be correlated with the occurrence and development of epithelial ovarian
      carcinoma.

PMID- 17441339
TI  - [Survivin expression in ovarian germ cell tumors].
AB  - OBJECTIVE: To investigate the relationship between the expression of survivin and
      the development of ovarian germ cell tumors (OGCT). METHODS: Survivin expressions
      in normal ovaries (n = 10) and ovarian germ cell tumors (n = 29) were detected
      with labelled streptavidin biotin method. RESULTS: No survivin protein was
      expressed in normal ovaries. Survivin protein was found in the cytoplasm and/or
      the nuclear of cells of 58.6% (17/29) of the ovarian germ cell tumor samples (P <
      0.05). There was no significant correlations between surviving protein and the
      pathologic types, stage, lymphonode metastasis, AFP and volume of ascites of the
      tumors (P > 0.05). CONCLUSION: High expression of survivin protein may trigger
      the pathogenesis of the ovarian germ cell tumors.

PMID- 17441340
TI  - [Expression of AIB1 protein in gynecological tumors].
AB  - OBJECTIVE: To investigate the expression of AIB1 (amplified in breast cancer 1)
      protein in gynecological cancers, and to analyze the role and clinical
      significance of AIB1 protein in carcinogenesis and development of gynecological
      cancers. METHODS: By immunohistochemical method SP, we examined the AIB1
      expression levels and relative clinico-pathological features in 10 normal
      cervical tissues and 18 cervical cancers; 18 normal endometrium tissues and 46
      endometrium carcinoma; 19 normal ovarian tissues and 74 epithelial ovarian
      cancers. RESULTS: The expression rate of AIB1 protein in cervical carcinoma
      wasn't higher than that in normal cervical tissues, but AIB1 expression was
      correlated with lymph node involvement. The positive expressions of AIB1 in
      carcinoma of endometrium and ovarian cancers were significantly higher than those
      in normal tissues. In carcinoma of endometrium, the rate of AIB1 expression in
      poorly-differentiated cancer was obviously higher than it in well-differentiated
      cancer. There was an inverse relationship between AIB1 expression levels and
      histological tumor grades (P = 0.02). It showed the tendency forward that the
      AIB1 expression increased with the progress of clinical stages (P = 0.006).
      CONCLUSION: The overexpression of AIB1 may play a role in the carcinogenesis and
      development of gynecological cancers, especially ovarian cancers.

PMID- 17441341
TI  - [Role of cyclooxygenase-2 in pulmonary microcirculation disorder in rats with
      acute pancreatitis].
AB  - OBJECTIVE: To identify the expression of Cyclooxygenase-2 (Cox-2) in lung tissues
      and its potential role in pulmonary microcirculation disorder in rats with acute
      pancreatitis. METHODS: The acute hemorrhagic and necrotic pancreatitis (AHNP)
      model was induced by the standard retrograde infusion of bilio-pancreatic duct
      with 4% sterile sodium taurocholate solution in Sprague-Dawley rats. The rats
      were randomly allocated into sham surgery group, AHNP group, and prophylactic
      celecoxib treated AHNP (C+ AHNP) group. The HE, phosphotungstic acid hematain
      (PTAH) and immunohistochemistrical (IHC) staining were employed to assess the
      dynamical alterations and interrelations of the histopathology, density of micro
      thrombus and Cox-2 expression of lung tissue respectively over a time course of
      3, 6, 12 and 24 hours. RESULTS: A significant and progressing increase in
      histopathologic scoring and Cox-2 expression in the lung tissues were found.
      There was a positive correlation between the Cox-2 expression and the
      histopathological scoring. A significant increase of pulmonary micro-thrombosis
      was detected at the early stage of the rat AHNP induced by sodium taurocholate,
      and the density of micro-thrombus was positively associated with the
      histopathological scoring. The prophylactic treatment with celecoxib, a highly
      selective inhibitor of Cox-2, attenuated the changes in histopathology, pulmonary
      micro-thrombosis and Cox-2 expression (P < 0.05). The down-regulated intensity of
      the Cox-2 expression by celecoxib was positively correlated with the improvement
      of the histopathology injury, but not with the change of the pulmonary micro
      thrombosis. CONCLUSION: The pulmonary microcirculation dysfunction caused by
      micro-thrombosis is an early event or even an enabler of the development of
      APALI. The over-expression of Cox-2 may have promoted the procoagulant activity
      which plays a key role in the development of pulmonary thrombus.

PMID- 17441342
TI  - [Effects of brain stem and spinal cord by isoflurane inhibiting nociceptive
      reflex].
AB  - OBJECTIVE: To explore the effect positions of the volatile anesthetic inhibiting
      the nociceptive reflex in the central nervous system. METHODS: Thirty adult SD
      rats were randomly and equally divided into two groups that the lip and hind paw
      of rats were held by clamp. The minimum alveolar concentration (MAC) was
      determined by clamping two places: one was to clamp the hind paw of rats, of
      which the nervous reflex is controlled via the spinal cord; the another group was
      to clamp the lip of rats, of which the nervous reflex is controlled through the
      brain stem. RESULTS: The isoflurane MAC was 1.44% +/- 0.09% in clamping the hind
      paw group, while 1.29% +/- 0.11% for clamping the lip group (P < 0.05).
      CONCLUSION: Both brain stem and spinal cord are the effect positions of volatile
      anesthetics (especially isoflurane).

PMID- 17441343
TI  - [The preliminary study on cord blood lymphocytes apoptosis in patients with
      intrahepatic cholestasis of pregnancy].
AB  - OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is a disease happening
      during pregnancy and does a great harm to the fetus. The etiology and
      pathogenesis of ICP are not clear. It is very important to investigate the
      relationship between ICP cord blood lymphocytes (CBLs) apoptosis and its clinical
      significance. METHODS: The CBLs were isolated from 20 patients with ICP and 20
      normal pregnant women. Flow cytometry (FCM) was used to detect the apoptosis
      cells in the CBLs. The apoptosis regulatory molecules (Fas/FasL, Bcl-2) of CBLs
      were detected by immunohistochemical technique. RESULTS: The percentage of
      apoptotic CBLs in ICP patients were significantly lower than that in the normal
      pregnant women (P < 0.05). The FasL protein expression of CBLs in ICP patients
      was significantly higher than that in normal pregnant women (P < 0.05), but Fas
      and Bcl-2 protein expression were normal. CONCLUSION: The abnormal apoptosis of
      CBLs may influence the immune reaction of ICP patients, which does something in
      the pathogenesis of ICP.

PMID- 17441344
TI  - [Role of extrinsic ganglioside GM1 in proliferation and differentiation of neural
      stem cells].
AB  - OBJECTIVE: To study the possible role of ganglioside GM1 in proliferation and
      differentiation of neural stem cells (NSCs) of rats in vitro. METHODS: (1) Fetal
      rats were employed to this study. The primary cells isolated from the cerebral
      cortex and hippocampus were cultured with serum-free incubation technique and
      then the cellular differentiation were induced with serum. (2) The proliferation
      and differentiation features of NSCs were observed under phase contrast
      microscope after the GM1 with different concentrations were added into NSCs' and
      serum-free DMEM/F12 culture media. RESULTS: (1) Comparing with control, no
      significant proliferation of NSCs was coming to pass when the GM1 with low
      concentration was added into the cell culture medium; however, the size of NSCs
      clones gradually decreased and the cells were dying when the GM1 with high
      concentration was added into NSCs' culture medium. (2) NSCs, cultured in DMEM/F12
      culture medium only containing GM1, neither proliferated nor differentiated, but
      were dying soon. CONCLUSION: GM1 of low concentration (12.5 microg/mL) has no
      significant influence on proliferation of NSCs, but GM1 of higher concentration
      can inhibit the NSCs' proliferation in culture medium.

PMID- 17441345
TI  - [The morphological alterations of jejunal mucosa accepting early enteral
      nutrition for post-operative patients with severe acute pancreatitis].
AB  - OBJECTIVE: To investigate the morphological alterations and significances of
      jejunal mucosa responsible to post-operative patients with severe acute
      pancreatitis treated with enteral nutrition (EN) or total parenteral nutrition
      (TPN). METHODS: 40 patients were divided randomly into EN group and TPN group.
      The serum levels of prealbumin (PAB) and transferrin (TRF) were detected at a
      given time. Jejunal mucosa specimens were acquired through a new technique and
      observed in detail both under general microscope and electronic microscope.
      RESULTS: On seventh and fourteenth post-operative day, the serum level of PAB in
      EN group was remarkably higher than it in TPN group (P < 0.05). No difference was
      seen in TRF levels of 2 groups. On 14th post-operative day, it was found by
      general microscope that the height of jejunal mucosa villi was significantly
      higher in EN group than in TPN group (P < 0.05), and meantime it was also found
      by electronic microscope that the height of microvilli on jejunal mucosa
      epithelial cells in EN group was remarkably higher than it in TPN group (P <
      0.05) and was higher than microvilli itself before EN start (P < 0.05). In TPN
      group, some pathological alterations could be seen in jejunal mucosa epithelial
      cells on 14th post-operative day, such as mitochondrial edema, crista swelling,
      dilation of rough endoplasmic reticulum and nucleolus, and the appearance of
      abnormal substances in intercellular attachments. However, none of above these
      pathological changes could be seen in EN group. CONCLUSION: Early enteral
      nutrition could protect the jejunal mucosa in post-operative patients with severe
      acute pancreatitis and have its results better than TPN alone.

PMID- 17441346
TI  - [Study on the correlation between resistance phenotype and expression level of
      femA of Staphylococcus aureus].
AB  - OBJECTIVE: To detect the expression level of femA of Staphylococcus aureus
      strains with different phenotype. METHODS: 15 strains of the non-beta-lactamase
      producing clinical isolates with different phenotype by agar dilution and by
      nitrocephin paper strip method were chosen as the object of test, in addition to
      4 donative strains (BB270, BB308, BB586, COL). Total RNA were extracted and
      analysed by agarose gel electrophoresis. Real time fluorescent quantitative PCR
      was performed to quantify the expression of femA gene. The expression level of
      femA of BB270 was set to be standard(100%). RESULTS: The expressions of femA were
      observed in all the tested strains. The amount of femA-specific mRNA in the
      mutant strain BB308 was approximately 37.82% and that of stain BB586 was 240.50%,
      homogeneous resistant strain COL was 862.61%. The amounts in MSSA strains were
      from 0.00353% to 29.92%, that in low-level MRSA strains were from 0.00554% to
      310%, otherwise that in high-level MRSA strains were from 13.88% to 55000%, which
      were different among these groups. There was no significant difference in amount
      of femA-mRNA between MSSA and low-level MRSA strains (P1 = 0.83) but marked
      between high-level MRSA and low-level MRSA/MSSA strains (P2 = 0.006, P3 = 0.01)).
      CONCLUSION: Expression level of femA in high-level MRSA was significant higher
      than that in low-level MRSA and MSSA. femA was essential for the expression of
      high-level methicillin resistance in MRSA.

PMID- 17441347
TI  - [Genetic polymorphisms at five STR loci in Chengdu Han population].
AB  - OBJECTIVE: To understand the allele structure and genetic polymorphisms at five
      STR loci in Chengdu Han population, to obtain a preliminary database and to
      analyze the value in forensic medicine. METHODS: EDTA-blood specimens were
      collected from unrelated individuals. The DNA of samples was extracted with
      Chelex-100 method. And then the PCR amplification, PAGE horizontal
      electrophoresis and gel silver staining were performed for analyzing the
      polymorphisms of five STR loci in Chengdu Han population. RESULTS: In the five
      STR loci,10, 7, 5, 7 and 7 alleles were found respectively. The observed
      heterozygosity of 83%, 80%, 64%, 66% and 77% and discrimination power of 95.44%,
      91.0%, 84.3%, 86.1% and 86.8% were identified for the five STR loci respectively.
      All loci obeyed Hardy-Weinberg equilibrium. CONCLUSION: The five STR loci display
      the high discrimination power. The obtained data are desirable for forensic
      analysis and benefiting to the research of the population genetics.

PMID- 17441348
TI  - [Effects of static magnetic field on the activity of superoxide dismutase of
      human gingival fibroblasts].
AB  - OBJECTIVE: To investigate the effects of static magnetic fields (SMF) generated
      by the open-circuit and closed-circuit dental magnetic attachments on the
      enzymology of human gingival fibroblasts. METHODS: In this study, a cellular SMF
      exposure system developed by our department of prosthetic dentistry was used to
      impose the static magnetic force on the cultured human gingival fibroblasts in
      vitro. The activity of superoxide dismutase in those fibroblasts of the test
      group and that of the control group were measured and compared. RESULTS: No
      significant difference (P > 0.05) in superoxide dismutase activity was found
      between the groups when they were loaded with different intensity of magnetic
      fields or for different period of time. CONCLUSION: Under the conditions in this
      experiment, the static magnetic fields of the open-circuit magnetic attachments,
      and those of the closed-circuit ones as well, have no biological effects on the
      superoxide dismutase of human gingival fibroblasts.

PMID- 17441349
TI  - [Effect of N-acetylcysteine on lipopolysaccharide induced preterm labor in mice].
AB  - OBJECTIVE: To test the effect of N-acetylcysteine (NAC) on the mice with
      infection associated preterm labor. METHODS: The pregnant C57BL/6 mice were
      randomly distributed into five groups, each with 20 mice and were given
      lipopolysaccharide (LPS), saline solution (NS), NAC, LPS+NAC (therapy), and NAC+
      LPS (prevention) respectively. The LPS (20 microg) was injected intraperitoneally
      to the mice every 12 hours since day 16 of gestation to induce preterm labor. The
      NAC was orally administered (0.5 g/kg) every 12 hours since day 15 or day 16 for
      the prevention and therapy groups respectively. The latency interval (from LPS
      injection to delivery of the first pup) and fetal survival rates were recorded in
      eight mice from each group. The remaining mice were killed at 4, 8, 12, and 24
      hours after the LPS injection (three for a group each time). The NF-kappaB
      activity and IL-8 mRNA in uterine and maternal and fetal hepatic GSH-PX and serum
      IL-8, MDA, and SOD were examined. RESULTS: The average latency interval of LPS
      treated mice was (15.1 +/- 1.9) hours, with a fetal survival rate of 4.3%. The
      NAC therapy extended the latency interval of LPS-treated mice to (35.4 +/- 2.1)
      hours, with a fetal survival rate of 69.0%. The NAC prevention extended the
      latency interval of LPS-treated mice to (44.8 +/- 2.6) hours, with a fetal
      survival rate of 84.3%. The expression of NF-KB P65 was activated and reached the
      peak 4 hours after the LPS injection. The uterine IL-8 mRNA and serum IL-8 and
      MDA reached the peak whereas the maternal and fetal hepatic GSH and SOD declined
      to the lowest 8 hours after the LPS injection. The NAC significantly inhibited
      the effect induced by the LPS (P < 0.01). CONCLUSION: The NAC has a therapeutic
      effect on the LPS-induced preterm labor in mice. It is even better to be used in
      preventing preterm labor. The mechanism of the protective effect of NAC may
      include the deactivation of the NF-kappaB/IL-8 and the reduce of the production
      of ROS.

PMID- 17441350
TI  - [The effect of ginkgolide B on astrocyte GFAP expression after the focal cerebral
      ischemia].
AB  - OBJECTIVE: To observe the effect of platelet activating factor (PAF) antagonist,
      ginkgolide B (GB), on the expression of glial fibrillary acidic protein (GFAP) in
      astrocytes during focal cerebral ischemia, of which the mechanism will be
      explored too. METHODS: The focal cerebral ischemia of tree shrews was induced to
      form via photochemical reaction. Morphological changes were observed by
      hematoxylin-eosin staining and electron microscopic technology. The GFAP
      expression in astrocytes was detected by immunohistochemistry. RESULTS:
      Morphological changes of the brain tissue occurred after focal cerebral ischemia.
      Astrocytes were more swollen with the prolongation of ischemia. The GFAP
      expression in astrocytes in the penumbra didn't change obviously at 4 h, but
      increased significantly at 24 h (P < 0.01), and retained the higher level at 72 h
      (P < 0.01) after focal cerebral ischemia. Whereas in contralateral cortex, the
      GFAP expression began to increase at 72 h (P < 0.05) after focal cerebral
      ischemia. With giving experimental animals GB at 6 h, the GFAP expression
      decreased until at 24 h after focal cerebral ischemia. CONCLUSION: GFAP
      expression in astrocytes increases after focal cerebral ischemia. And by
      inhibiting the astroglial GFAP expression, the ginkgolide B exerts the cerebral
      protective effects.

PMID- 17441351
TI  - [The effect of glucocorticoid on IL-8 expressing in lung tissue of rat with
      chronic obstructive pulmonary disease].
AB  - OBJECTIVE: To explore the role of IL-8 in the pathogenesis of chronic obstructive
      pulmonary disease (COPD) and the effect of glucocorticoid on COPD. METHODS: 24
      health males of Wistar rats were randomly divided into three groups (group A:
      normal control group, group B: COPD model group, group C: group pretreated with
      prednisone), of which each got 8 rats for this study project. Rat COPD model was
      established by exposing rat to cigarette smoke daily for 120 days. The prednisone
      was, via stomachal injection, given to the rats of group C with a dose of 5 mg/kg
      on every other day just before rats exposed to cigarette smoke. After COPD model
      was set up, the bronchoalveolar lavage (BAL) was performed. The total cells and
      neutrophils in bronchoalveolar lavage fluid (BALF) were counted for examination,
      and the levels of IL-8 and TNF-alpha in supernatants of BALF and serum were
      detected by ELISA. The lung tissue section stained by HE was observed in order to
      study the alternation of morphology, and also measured in terms of mean lining
      interval (MLI), mean alveolus number (MAN) and percentage of alveolar area in
      total area (PAA). RESULTS: MLI and PAA in group B were higher than those in group
      A (P < 0.01), and decreased after pretreatment with prednisone (P < 0.01), in
      which however MAN was just on the contrary. The statistic analysis showed that
      levels of IL-8 [(114.5 +/- 15.7) pg/mL vs (259.4 +/- 20.1) pg/mL, respectively, P
      < 0.01], TNF-alpha [(80.5 +/- 9.5) pg/mL vs (145.9 +/- 17.3) pg/ mL, P < 0.01],
      total cell counts [(1.64 +/- 0.12) x 10(8)/L vs (5.76 +/- 0.29) x 10(8)/L, P <
      0.01], neutrophil counts [(0.099 +/- 0.065) x 10(8)/L vs (1.26 +/- 0.25) x
      10(8)/L P < 0.01], neutrophil proportion [(5.9 +/- 3. 6)% vs (21.8 +/- 3.7)%, P <
      0.05] in BALF of group B were higher than those of group A. After pretreatment
      with prednisone, the above measured values were significant reduction (P < 0.01
      or 0.05). The level of IL-8 in serum of group B was higher than that of group A
      [(45.2 +/- 13.5) pg/mL vs (85.7 +/- 7.0) pg/mL, P < 0.01], but which, after
      pretreatment, there was reduction but no significance (P > 0.05). The positive
      correlation was demonstrated among the levels of IL-8, TNF-alpha and counted
      neutrophils in BALF of group B, but not between the level of IL-8 and TNF-alpha
      in serum. CONCLUSION: There is a close correlation between IL-8 in BALF and
      airway inflammation with COPD. The IL-8 cooperating with TNF-alpha may be
      responsible for the persistence and amplification of airway inflammation with
      COPD. By modulating the expression of IL-8 gene, inhibiting granulocyte
      chemotaxis and degranulation, the prednisone may relieve airway inflammation, and
      relieve the lesion of airway resulting from inflammatory cytokines and cells,
      hence postpone the progress of COPD.

PMID- 17441352
TI  - [Effect of rosiglitazone on integrin beta1 expression and apoptosis of proximal
      tubular cell exposed to high glucose].
AB  - OBJECTIVE: To evaluate the effect of rosiglitazone (ROS) on integrin beta1
      expression and apoptosis of proximal tubular cell exposed to high glucose.
      METHODS: The proximal tubular cells of rats were cultured in vitro and divided
      into 6 groups: control group, normal glucose (5 mmol/L) group, high glucose (30
      mmol/L) group, only ROS (10 micromol/L) group, glucose (30 mmol/L)+ROS (5
      micromol/L) group, and glucose (30 mmol/L) +ROS (10 micromol/L) group. The cells
      were cultured for 48 hrs and the integrin beta1 expressions were detected by
      Western blot and RT-PCR; The apoptosis was evaluated by flow cytometry after the
      cells were cultured for 24, 48, 72 hrs. RESULTS: The expressions of integrin
      beta1 protein and mRNA of high glucose (30 mmol/L) group were significantly
      increased as compared with control group and normal glucose (5 mmol/L) group. The
      integrin beta1 of glucose (30 mmol/L)+ROS (5 or 10 micromol/L) group was
      decreased as compared with high glucose group (P < 0.05). Flow cytometry
      demonstrated the decreased apoptosis to be with time-dependence. CONCLUSION: ROS
      can strikingly inhibit the expression of integrin beta1 in proximal tubular cells
      exposed to high glucose, with a marked dose-dependent manner. The effect of ROS
      on cell apoptosis may be relevant to integrin beta1.

PMID- 17441353
TI  - [Effect of PPAR-gamma ligand RGZ on inhibiting the cell proliferation of
      cholangiocarcinoma].
AB  - OBJECTIVE: To investigate the effect that PPAR-gamma (peroxisome proliferator
      activated receptor gamma, PPAR-gamma) ligand rosiglitazone (rosiglitazone, RGZ)
      inhibits the cell proliferation of cholangiocarcinoma. METHODS: The cell line
      QBC939 of cholangiocarcinoma was interfered with different concentration of RGZ,
      and then calculated for the rate of cell proliferation inhibited at different
      concentration. The change of cell cycle and the rate of cell apoptosis at each
      concentration were detected by FCM. RESULTS: RGZ showed the significant effect on
      inhibiting the cell proliferation of cholangiocarcinoma, especially on the 1200
      mg/L concentration group. The highest inhibited rate of QBC939 cell proliferation
      could be up to 83.66%. After RGZ used to treat the cultured QBC939 cell for 48 h
      and 72 h, the inhibited rates of QBC939 cell proliferations of 1200 mg/L, 600
      mg/L,300 mg/ L,150 mg/L, 75 mg/L and 37.45 mg/L groups were compared to those of
      control group, and with the statistics result of P < 0.001. Meanwhile the cell
      cycles were controlled significantly as well, 62.77% of the cells were detained
      in stage G0/G1. CONCLUSION: In vitro PPAR-gamma ligand rosiglitazone has the
      significant proliferation inhibition effect to cell lines QBC939 of
      cholangiocarcinoma.

PMID- 17441354
TI  - [Effect of Psidium guajava leaf extract on alpha-glucosidase activity in small
      intestine of diabetic mouse].
AB  - OBJECTIVE: To investigate the inhibition effect of Psidium guajava linn (PGL), a
      leaf water-soluble extract, on the activities of alpha-glucosidases. METHODS: The
      PGL water-soluble extract (PGL WE) was obtained by the procedure of distilled
      water immersion, filtration, extracted fluid concentration and dry of Psidium
      guajava leaf. The diabetes of Kunming mice was induced by intraperitoneal
      injection of Streptozotocin (STZ). The small intestinal mucosa of diabetic mice
      was scraped to make the homogenate for the preparation of alpha-glucosidases. In
      vitro, the homogenates were incubated with sucrose and maltose. The formed
      glucose represented the activities of alpha-glucosidases. The Lineweaver-Burk
      plot was applied to determine the type of alpha-glucosidase activity inhibited.
      RESULTS: The water-soluble extract from PGL significantly inhibited, in the dose
      dependent manner, the activities of alpha-glucosidase from small intestinal
      mucosa of diabetic mice. The PGL extract inhibition concentration (IC50) to
      sucrase or maltase was 1.0 g/L or 3.0 g/L respectively. The mixed inhibition type
      was showed to be the competitive and non-competitive inhibition. CONCLUSION: The
      GPL water-soluble extract possesses the potential effect of inhibition on the
      alpha-glucosidase activity from the small intestinal mucosa of diabetic mouse.

PMID- 17441355
TI  - [Effect of Aurora A on biological phenotypes of prostate cancer cells].
AB  - OBJECTIVE: To examine the effect of Aurora A on the biological phenotypes of
      prostate cancer cells and the role of Aurora A in the carcinogenesis of prostate
      cancer. METHODS: Full length Aurora A gene was cloned and transfected into the
      prostate cancer cell line LNCaP to construct a positive cell clone with high
      expression of Aurora A. The growth and proliferation of the cells was detected by
      MTT. The mobility of the cells was examined by transwell cell layer infiltration
      assay. The growth and motility of LNCaP-Aurora A cells were compared with those
      of the LNCaP-pcDNA3. 1/LNCaP cells. RESULTS: Compared to the LNCaP-pcDNA3. 1/
      LNCaP cells, the cells with high expression of Aurora A had faster proliferation
      and stronger invasive ability. Three days after cultivation, more LNCaP-Aurora A
      cells had grown than the LNCaP-pcDNA3. 1/LNCaP cells (P < 0.05). CONCLUSION: The
      increased expression of Aurora A is closely associated with the malignant
      phenotypes of prostate cancer. Aurora A may play a very important role in the
      carcinogenesis of prostate cancer.

PMID- 17441356
TI  - [Study on the relationship between Aurora A expression in cancer cell and
      treatment efficacy of taxol for prostate cancer].
AB  - OBJECTIVE: To explore the relationship between Aurora A expression and cell
      sensitivity to taxol, and elucidate the effect of Aurora A on the treatment
      efficacy of taxol for prostate cancer. METHODS: A cell clone highly expressing
      Aurora A was constructed through transfected with full length Aurora A gene, and
      then termed as Du145-Aurora A. Cells were treated with different dose taxols. The
      growth inhibition rates of cells were detected by MTT assay, and the cell
      apoptosis rates were detected through flow cytometry. The growth inhibition and
      apoptosis rates of Du145-Aurora A and Du145 cells were compared for Aurora A up
      regulated expression. Simultaneously, cells Du145-Aurora A were treated with
      DNAzymes for down-regulating the Aurora A expression, and then the variations of
      cell growth inhibited rate and apoptosis rate were detected. RESULTS: Up
      regulation of Aurora A expression reduced the cell inhibition and apoptosis rates
      when treated by taxol, but the down-regulation of Aurora A expression after
      DNAzymes applied increased the cell inhibition and apoptosis rates when treated
      by taxol. CONCLUSION: There is a positive relationship between Aurora A
      expression and treatment efficacy of taxol for prostate cancer, and inhibiting
      Aurora A expression will enhance the treatment efficacy of taxol for prostate
      cancer.

PMID- 17441357
TI  - [Experiment study on the diagnostic value of bile K-ras gene mutation responsible
      to the hepatic metastasis of pancreatic cancer].
AB  - OBJECTIVE: To investigate the early diagnosis value of bile K-ras mutation
      responsible for hepatic metastasis of pancreatic cancer. METHODS: While building
      the animal models with pancreatic cancer and hepatic metastasis of pancreatic
      cancer of rats, we collected bile from the model animals, and used the polymerase
      chain reaction and restriction fragment-length polymorphism (PCR-RFLP) to
      evaluate the point mutation at exon codon 12 of K-ras gene in bile. Then, the
      above result was compared with pathological slice. RESULTS: The positive rates of
      K-ras point mutation in bile were 84.2% (16/19) for the model with hepatic
      metastasis of pancreatic cancer, and 0.0% (0/16) for the model with pancreatic
      cancer without hepatic metastasis. For the model with hepatic metastasis of
      pancreatic cancer, the sensitivity, specificity, positive prediction or negative
      prediction value of surveying K-ras mutation in bile was 84.2%, 85.7%, 84.2% or
      85.7% respectively. CONCLUSION: Both the mutability and the specificity of K-ras
      gene mutation at codon 12 in bile are high. Our above work can supply a new
      elemental filter method for the early diagnosis of hepatic metastasis of
      pancreatic cancer.

PMID- 17441358
TI  - [The clinical diagnosis value of fibro-optic bronchoscope examination combined
      with tumor marker determination to lung cancer].
AB  - OBJECTIVE: To investigate the diagnosis value of fibro-optic-bronchoscope
      combined with tumor maker determination to lung cancer. METHODS: By fibro-optic
      bronchoscope (FB) and electrochemiluminescence (ECL) examinations, 98 cases with
      lung cancer and 88 cases with benign lung disease were studied for calculating
      the detectable sensitivity and specificity to lung cancer, then further for
      evaluating the clinical value of FB examination combined with detection of tumor
      marker in serum/pleural fluid of patients with lung cancer. Results In patients
      with lung cancer, the serum levels of CEA, CA125 and CYFRA21-1 were (46.34 +/-
      18.28) ng/mL, (83.34 +/- 33.26) U/mL and (25.67 +/- 10.32) ng/mL respectively,
      which were higher than those in patients with benign lung diseases. The serum
      levels of above three tumor markers in patients with lung cancer all were
      significantly higher than those in patients with benign lung diseases (P < 0.05).
      In the 36 specimens of pleural fluid, three tumor markers were higher than those
      in the corresponding serum samples. The detectable sensitivity of each tumor
      marker in pleural fluid was higher than that in serum. The sensitivity,
      specificity and overall accuracy of CEA in lung cancer were 37.5%, 87.5% and
      63.6% respectively, of CA125 were 67.7%, 40.9% and 54.9%; of CYFRA21-1 were
      56.3%, 81.8% and 68.5%; of FB were 60.4%, 100.0% and 79.4% respectively. The
      sensitivity, specificity or overall accuracy of fibro-optic bronchoscope combined
      with tumor marker (TM) examination to diagnosis of lung cancer was 90.6%, 92.0%
      or 91.3% respectively. CONCLUSION: The FB examination is valuable in diagnosing
      lung cancer, and by combined with TM determination, can further improve the
      accuracy to diagnosis of lung cancer.

PMID- 17441359
TI  - [Factors influencing the use of health care services from patients with COPD in
      Chengdu].
AB  - OBJECTIVE: To investigate the use of health care services by COPD patients and to
      identify factors that shape the pattern of services utilization. METHODS: All of
      the COPD patients who lived in the six randomly selected communities with
      community health services in 2003 were surveyed. A total of 446 patients
      completed the interview-administered questionnaires. The medical records of those
      patients were also reviewed and abstracted if possible. The questions asked in
      the survey included: social and demographic information, COPD related knowledge
      and attitudes, use of health care services and medical expenditure associated
      with the services in the past year. RESULTS: About half (53.04%) of the COPD
      patients used the outpatient services, with an average visits of 6.04 +/- 4.05
      per year. Eighteen percent of the patients had been hospitalized, with an average
      of 6.10 +/- 2.61 episodes of hospitalizations in one year and an average of
      length of stay of (51.65 +/- 15.91) days. The COPD patients used large
      comprehensive hospitals (45.33%) more often than the community health services
      (18.22%). Age, past experiences and attitudes towards COPD, severity of illness
      and out of pocket payment had significant impact on patients' choice of
      outpatient services. Occupation, past experiences, out of pocket payment,
      severity of illness and family attitudes had significant impact on patients'
      choice of hospital services. Education, income, occupation, out of pocket payment
      and attitudes towards COPD had significant impact on patients' choice of
      community health services. CONCLUSION: Underutilization of community health
      services by COPD patients is obvious in Chengdu. Given the diverse range factors
      that influence patients' choice of services, governmental intervention is needed
      to encourage the use of community health services.

PMID- 17441360
TI  - [Establishment of orthotopic model of MG-63 osteosarcoma].
AB  - OBJECTIVE: To establish an orthotopic transplantation model of human osteosarcoma
      in nude mice. METHODS: The cell suspensions of serial passage of MG-63 cell line
      with high tumor formation rate were implanted into the distal femur of nude mice.
      The tumor tissue were treated with routine pathologic HE stain and observed under
      microscope, and made to the x-ray inspection. RESULTS: In two weeks, the neoplasm
      was found to grow at local tissue of nude mice, and also found in x-ray film when
      it was after implant operated for 4 weeks. The typical characteristics of
      osteosarcoma of tumor tissue were found under microscope. The tumor formation
      rate of tumor tissue transplantation was 100% and the tumor formation rate of MG
      63 cell suspension was 70%. CONCLUSION: The orthotopic transplantation model of
      osteosarcoma in nude mice is well established and provides a more similar human
      internal milieu for researches of osteosarcoma.

PMID- 17441361
TI  - [Three-dimensional finite element analysis responsible to bone cement with
      customized prosthesis of proximal segmental femur].
AB  - OBJECTIVES: To create three-dimensional finite element models for the large
      defect of proximal femur and the customized prosthesis of proximal segmental
      defect femur, and to analyze the influence on the stress distribution of femur
      cement after the intramedullary implantation of different stem length prostheses.
      METHODS: Three-dimensional finite element models were established for the large
      defect of proximal femur and proximal femoral segmental prostheses with different
      stem-lengths (140 mm, 120 mm, 100 mm, 80 mm and 60 mm). The influence on stress
      distribution of femur-cement was analyzed for the different stem-length
      prostheses implanted. RESULTS: The stress on bone cement gradually increased from
      proximal end to distal end, and reached its highest value near the tip of
      prostheses. The prostheses with stem lengths of 120 mm, 100 mm, 80 mm and 60 mm
      could bring the cement mantle stress to the value beyond the fatigue strength of
      cement. Only when the intramedullary stem-length of prosthesis was 140 mm, the
      stress on the cement mantle was under the fatigue strength of cement. CONCLUSION:
      The intramedullary stem of the proximal femoral segmental prosthesis must have
      enough length to decrease the stress on the cement mantle in order to avoid the
      prosthesis loosening.

PMID- 17441362
TI  - [Purification of human VLDL apolipoproteins by middle pressure liquid
      chromatography].
AB  - OBJECTIVE: To purify human VLDL apolipoproteins by middle-pressure liquid
      chromatography. METHODS: Human VLDLs were isolated by one step density
      ultracentrifugation. Delipided human VLDL was separated by Sephacryl S-200
      molecular sieve chromatography. ApoE was purified by heparin Sepharose CL-6B
      affinity chromatography. ApoC I ,C II and C III were purified from apoC. fraction
      by DEAE-Sephacel ion exchange chromatography: RESULTS: Purified apoE, apoC I,
      apoC II and apoC III were obtained. SDS-PAGE and immunodiffusion tests indicated
      the isolated proteins were pure. CONCLUSION: We have established a purification
      procedure for human VLDL apolipoproteins with highly efficiency and simplicity by
      MPLC.

PMID- 17441363
TI  - [Acute myelomonocytic leukemia occurred after multiple myeloma treated: a case
      report].
AB  - We reported a case of multiple myeloma, who suffered from the acute
      myelomonocytic leukemia (AML-M4) after the chemotherapy of alkylating agent. The
      patient had a history of multiple myeloma and was treated with the regimen of
      including L-Sarcolysinum and cyclophosphamide for 5 years. The multiple myeloma
      of this patient was proved to have got the remission through bone marrow
      aspiration, immunofixation electrophoresis of serum, serum protein
      electrophoresis and detection of urine light chain. However, a pancytopenia of
      unknown cause was verified to peripheral blood. During the course of supportive
      treatment only with blood cell and platelet transfusion, WBC count of this
      patient showed a rising trend and the blast cells (8%-15%) started to occur in
      the peripheral blood. The further examination discovered that the ratio of blast
      cell was beyond 30% in bone marrow smear, and the flow cytometry detected the
      CD45, HLA-DR, CD13, CD33, CD64 to have the positive expressions. Thus, the
      diagnosis of multiple myeloma in remission and secondary AML-M4 was established.
      When the chemotherapy regimen to AML was being planned for this patient, she died
      of massive hemorrhage of gastrointestinal tract due to thrombocytopenia and
      ineffectiveness.

PMID- 17441364
TI  - [Analysis of selected inflammatory markers in patients with stable renal graft
      (RTx) 36 months after transplantation].
AB  - Chronic inflammation is an inherent feature of chronic renal failure. Successful
      renal transplantation (RTx) is the only known renal replacement therapy
      sufficient to reverse most of the metabolic disturbances of chronic uremia,
      although still some of these abnormalities may be present or even new problems
      may occur (mostly as the side effects of immunosuppressive drugs). The aim of
      this study was to evaluate the level of inflammation in 20 patients (9 F, 11 M,
      aged mean 44.0 +/- 11.8 years) with well-preserved renal function 36 months after
      kidney transplantation, using serum levels of selected cytokines (IL-6, IL-18,
      TNFalpha and soluble receptor for TNF - sTNFRII), acute phase proteins (CRP,
      fetuin A) and hepatocyte growth factor (HGF). Procalcitonin was also assessed as
      the sensitive indicator of active infection. Obtained results were compared with
      the control group of healthy subjects in a respective age. Serum levels of IL-6,
      TNF-R and IL-18 were significantly higher, and HGF and fetuin A--significantly
      lower in patients vs. controls (p < 0.05 for all differences). Significant
      negative correlations were noted between glomerular filtration rate (GFR) and
      serum TNF, sTNFRII and IL-18 in RTx patients, whereas strong positive
      relationship between GFR and fetuin A was observed. Serum creatinine correlated
      with IL-6, IL-18, TNFalpha, sTNFRII and hsCRP levels and serum urea-with
      TNFalpha, sTNFRII, IL-6 and IL-18. Significant negative associations were also
      noticed between serum fetuin A and most of the tested inflammatory markers:
      sTNFRII (r = -0.77; p = 0.0005), IL-6 (r = -0.63; p = 0.009), hsCRP (r = -0.62; p
      = 0.009) and IL-18 (r = -0.60; p = 0.01). Obtained results permit us to conclude
      that the increased activity of inflammation can still be noticed in RTx patients
      36 months after successful engraftment. This process is inversely associated with
      the level of kidney function. The role of fetuin A as the 'negative' acute phase
      protein was also demonstrated in this group of patients.

PMID- 17441365
TI  - [Selected problems of the nephrological and urological status of women with
      Turner's syndrome].
AB  - Nephrological and urological problems among women with Turner's syndrome (TS)
      have not been frequently investigated so far. The aim of our study was to address
      those issues in adult women with TS in Poland. 176 women with TS, whose age was
      between 18 and 51 years, who presented to our center from the whole territory of
      Poland between March, 1995 and December, 2002 were examined. A particular
      attention was payed to nephrological and urological status of those patients. 61
      women (34.7%) presented with inflammatory status in urinary tract. In 24.6% of
      them anatomical, congenital defects of the urinary tract were discovered. Both
      the presence of inflammation as well as a defect itself have no influence on
      incidence and degree of arterial hypertension, diabetes mellitus, antropometric
      parameters of those patients with TS and other, laboratory parameters assessed.
      CONCLUSIONS: 1. Women with TS suffer from urinary tract inflammations
      significantly more frequently then it happens in general female population. 2.
      Urinary tract diseases among women with TS, associated with leukocyturia are
      either not related to, or related not only to the characteristics of the type of
      a particular congenital defect of the urinary tract.

PMID- 17441366
TI  - [The primary prophylaxis of neural tube defects in the Podkarpacian region].
AB  - The paper presents results of investigations carried out in years 2002/ 2003 on
      prevalence of primary prophylaxis of neural tube defects among children 0 to 3
      years old. Subjects were 222 healthy mothers residing in the Podkarpacian region.
      The results indicate that primary prophylaxis of neural tube defects is
      propagated quite poorly in this region. A dominant role in its spreading play
      physicians and at the same time, other sources of knowledge are marginal. There
      is a strong need for intensification of activities of this kind.

PMID- 17441367
TI  - [Direct surgical outcome of meningiomas obliterating the superior sagittal
      sinus].
AB  - BACKGROUND AND PURPOSE: Aggressive surgery for parasagittal meningiomas is
      considered when superior sagittal sinus is totally thrombosed by the tumour.
      However, there is potential risk of venous outflow injury resulting in an
      intracerebral haemorrhage. The aim of this study is to present surgical technique
      and early surgical outcome of patients with meningiomas obliterating the superior
      sagittal sinus. MATERIAL AND METHODS: Ten patients (4 men and 6 women, mean age
      58), operated for sagittal meningiomas with radiologically proved superior
      sagittal sinus obliteration, were analysed retrospectively. In all cases, radical
      surgery with the resection of invaded sagittal sinus was performed. The size of
      tumours varied between 35 and 100 mm; the mean was 53 mm. Five of them required
      reoperation because of tumour recurrence due to a previous incomplete resection.
      In five cases, bifrontal craniotomy was made, in four biparietal and in one
      parieto-occipital. Preoperative status and direct postoperative outcome were
      compared using the Karnofsky scale. RESULTS: Very good outcome was achieved in 6
      cases--the clinical status remained unchanged. In two, the outcome was good (in
      the first patient hemiparesis increased and in the second there was worsening of
      cortical visual disturbances). In two cases with an unfavorable outcome, one
      patient suffered quadriparesis and mutism; the other experienced cerebral edema
      with hemorrhagic infarct and died despite decompressive surgery. Both these
      patients were totally dependent before surgery (Karnofsky < 40). CONCLUSIONS: In
      the radical resection of a tumour with occluded sinus, direct postoperative
      outcome ranges from good to very good in a significant number of cases. In
      dependent patients having a large tumour, there is the risk of an unfavourable
      outcome after radical surgery. In such cases, partial resection and further
      radiotherapy should be considered.

PMID- 17441368
TI  - [Vascular abnormalities in patients with primary intracerebral hemorrhage].
AB  - BACKGROUND: To prevent the recurrence of primary intracerebral hemorrhage (PIH)
      it is important to identify patients with underlying structural vascular
      abnormalities (VA). According to previous study data-- the site of hemorrhage,
      the patient's age and pre-existing hypertension affect the likelihood of finding
      VA. However, the indications for angiography, the gold standard for the diagnosis
      of VA, still remain controversial. PURPOSE: To assess the frequency of VA and to
      determine features that might increase the probability of finding VA in patients
      with PIH. MATERIAL AND METHODS: 100 patients with PIH, without a history of
      trauma, coagulopathy, or known pre-existing brain abnormality, who were admitted
      to the Stroke Unit of the Department of Neurology, Jagiellonian University,
      between January 1999 and November 2000 entered this prospectively designed study.
      In the group of 96 patients, 53 persons underwent conventional angiography within
      14 days of stroke onset (in 4 cases we found bleeding into the tumor and these
      patients were not included in further analysis). RESULTS: Vascular abnormalities
      were found in 14 of 53 patients (26.4%); ruptured aneurysms in 9 patients
      (17.0%), arteriovenous malformations (AVM) in 3 patients (5.7%), venous angioma
      in 1 patient (1.8%) and cavernous angioma in 1 patient (1.9%). Vascular
      malformations were found in 12 of 25 patients with lobar hemorrhage, in 1 of 8
      patients with hemorrhage originating in the thalamus and in 1 of 2 patients with
      hemorrhage originating in the pons. Angiographic findings were negative in 8
      patients with hemorrhage in the periventricular white matter, in 8 with
      hemorrhage originating in the basal ganglia and in 2 patients with hemorrhage in
      the cerebellum. Patients with VA were significantly younger than patients without
      VA (49.9 +/- 11.7 years and 58.7 +/- 13.3 years respectively, p = 0.03) and they
      had a history of hypertension significantly less often (50.0% and 89.7%, p =
      0.001). Intraventricular hemorrhage and subarachnoid bleeding occurred in a
      similar percentage of patients with ICH, independent of whether or not they had
      VA (28.6% and 38.5%; 21.4% and 10.3% respectively, p = n.s.). CONCLUSIONS: (1) A
      vascular abnormality is the cause of about 26% of ICH, with a higher likelihood
      in younger patients and with lobar hemorrhage. (2) A history of hypertension does
      not exclude the presence of VA. (3) Intraventricular hemorrhage or subarachnoid
      bleeding does not predict the presence of VA.

PMID- 17441369
TI  - [Quality of life assessment in patients after the embolization of aneurysms of
      cerebral arteries].
AB  - THE OBJECTIVE OF THE PAPER: The objective of the paper has been to assess the
      quality of the patients lives after subarachnoid haemorrhage and the embolization
      of aneurysms of cerebral arteries, and to specify correlations between different
      aspects of the patients life under examination and selected socio-demographic
      factors. MATERIAL AND METHOD: The examination covered 28 patients having been
      subject to embolization of aneurysms of cerebral arteries including 12 women and
      16 men at the age of 33 up to 62 (48.4 years of age on average) in the years 2000
      2002. A 6- month period at least after embolization served as a major criterium
      for selecting respective patients to be examined. The control group covered 30
      healthy people (including 16 women and 14 men) at an average age of 46.2. The
      examination was made on the basis of the Polish version of questionnaire RNL
      Index (Reintegration to Normal Life Questionnaire). Medical documentation from
      hospital archives served as an additional source of data. RESULTS: The most
      numerous group (56%) included patients between 40 and 50 years of age. 82% of
      patients lived in towns, for 61% of patients disability pension constituted the
      only source of income. All patients were hospitalized on an instant basis. 82.1%
      of patients suffered from headaches, 50% of patients suffered from nausea, vomits
      and eyesight disturbances, 40.9% of patients were diagnosed with one-side
      paresis, and 57.1% of patients under examination suffered from loss of
      consciousness. After embolization 85.7% of patients experienced mood swings,
      57.1% of patients suffered from vision disorders, 39.3% had phonological
      impairments. 25% of patients suffered from epilepsy. After embolization 75% of
      patients were subjected to the convalescence process. The comparison of RNL Index
      in respective aspects of the patients life before and after embolization
      indicated its substantial decrease in the group of patients subject to
      embolization. There was a big difference in physical self-sufficiency, work,
      education and recreation. There was no correlation between the quality of the
      patients lives after embolization and sex, age, domicile and the fact of living
      together with other family members. There was a plus correlation (R = 0.48) for
      the quality of life and education. Patients with higher education assessed the
      quality of their lives as being much higher. CONCLUSIONS: The quality of the
      patients lives after the subarachnoid haemorrhage and the embolization of
      aneurysms of cerebral arteries worsened to a great extent resulting from RNL
      Index decreasing from 98.0 to 71.5. The illness had the most negative influence
      on professional career, sociable life and how to cope with everyday situations.
      The quality of the life the embolization of cerebral arteries did not differ much
      from that of the people from the control group. No influence of sociodemographic
      factors on the quality of the patients lives under examination was indicated.

PMID- 17441370
TI  - [Epileptic seizures in the vascular malformations in children].
AB  - OBJECTIVES: Cerebral vascular anomalies have been rare pathology of the brain in
      childhood. The most frequent clinical symptoms of them are: intracerebral
      hemorrhage, subarachnoid hemorrhage, headache, neurological deficits and
      epilepsy. AIM: Because of very few reports about epilepsy in cerebral vascular
      anomalies in children the authors continued studies in this subject. MATERIAL AND
      METHODS: The subject of the study were 20 patients in the age between 5 to 15
      years with cerebral vascular anomalies hospitalized in the Department of
      Developmental Neurology Medical University of Gdansk in the years 1980-2001. The
      clinical state and CT, MRI, angiography and EEG recordings were evaluated in all
      the patients. Arteriovenous malformations (AVM) were diagnosed in 13 (65%), in 5-
      angioma cavernous (25%), in 2--aneurysms (10%). RESULTS: In 4 children epilepsy
      was the first symptom of cerebrovascular anomalies. Epileptic seizures were
      observed in 4 patients in the acute stage of the disease. In 6 children epilepsy
      was the consequence of arteriovenous malformation. CONCLUSION: Epilepsy occurred
      in 50% of children with vascular malformations. Among cerebrovascular anomalies,
      arteriovenous malformations are the most frequent cause of epilepsy in the group
      of examined children.

PMID- 17441371
TI  - [Percutaneous transluminal septal myocardial ablation: early results and long
      term follow-up].
AB  - BACKGROUND: Percutaneous transluminal septal myocardial ablation (PTSMA) is
      becoming an alternative to surgical myectomy in the treatment of severe, drug
      refractory, hypertrophic obstructive cardiomyopathy (HOCM). The aim of our study
      was to analyze early results, complications and long-term follow-up in patients
      after PTSMA. METHODS: Out of eighteen patients [11 M] initially accepted for
      PTSMA, the procedure was performed in 12 patients [6 M] age from 22 to 70 y. All
      the patients underwent clinical evaluation, echocardiography and cardiopulmonary
      exercise testing (CPX) before the procedure, and after a median of 38 months of
      observation. In echo-cardiography left ventricle outflow tract gradient (LVOTG)
      and intraventricular septum diastolic diameter were assessed. The following
      parameters of CPX were analyzed: exercise duration, anaerobic threshold, peak
      oxygen consumption, peak exercise heart rate and carbon dioxide ventilating
      equivalent. RESULTS: The procedure was successful in 11 patient. There were 2
      acute complications: 3rd degree AV block requiring peacemaker implantation and
      LVOTG increase with SAM exacerbation requiring urgent cardiosurgical
      intervention. During long-term follow-up 1 cerebral stroke and 1 death occurred.
      PTSMA resulted in significant reduction of left ventricle outflow tract gradient
      (89 +/- 44 vs. 17 +/- 17 mmHg) and intraventricular septum diastolic diameter (24
      +/- 4 vs 18 +/- 5 mm) (p < or = 0.01 for both). We also observed improvement of
      CPX parameters: exercise duration (487 +/- 268 vs. 730 +/- 292 sec), anaerobic
      threshold (34.3 +/- 8.9 vs. 53.2 +/- 13.4% VO2max predicted), peak oxygen
      consumption (18.5 +/- 6 vs. 26.8 +/- 10.1 ml/kg/min), peak exercise heart rate
      (70.3 +/- 8.3 vs. 83.6 +/- 11.7%) and carbon dioxide ventilating equivalent (31
      +/- 6.1 vs. 28 +/- 4.8); (p < or = 0.01 for all). CONCLUSIONS: PTSMA is an
      effective method of treatment in patients with severe, drug refractory HOCM.
      PTSMA is safe and is associated with a low percentage of severe complications.

PMID- 17441372
TI  - [Socioeconomical status of life and regularity of intake of medicines among
      hypertensive patients].
AB  - As hypertension occurs very commonly in contemporary population, its
      complications and costs of treatment are one of the most important health and
      social issues. Non-compliance of the patients with respect to the intake of
      medicines and not-obeying medical instructions on healthy life style are said to
      be an important cause of hypertension treatment failures. Socioeconomic status of
      life has also a strong impact on the regularity of medicine intake. The goal of
      this article was to analyze the influence of social and economical factors on the
      regularity of medicine intake in hypertensive patients. The test group consisted
      of 222 patients (20-80 years old (x = 56.85 +/- 8.59); 123 women and 99 men, all
      of whom were treated in the out-patient department in the First Department of
      Cardiology of the Jagiellonian University Medical College in Cracow. The impact
      of place of living, education, professional activity, income, knowledge about the
      illness and the goal of hypertension treatment on the regularity of medicine
      intake was assessed using a specially elaborated assessment questionnaire. The
      patients were divided into two categories depending on their compliance and
      extend to which they followed doctor's recommendation concerning the need of
      regular medicine intake (129 persons with regular intake and 93 persons with
      irregular medicine intake). Within the study groups, statistically significant
      differences concerning analyzed parameters were observed. Regular medicine intake
      was more common among city citizens (64.91%), persons with secondary education
      (69.69%), with higher education (71.69%), with employment status (67.44%), with
      higher average income and regularly checking their blood pressure at home at
      least once per week (66.85%). CONCLUSIONS: Socioeconomic factors have a decisive
      influence on following the instructions on hypertension by the patients. Special
      care is needed in the treatment of hypertensive patients with low socioeconomic
      status.

PMID- 17441373
TI  - [Selected birth outcomes as prognostic determinants of hypertension in children].
AB  - BACKGROUND: About 5-15% of children suffer from hypertension. The influence of
      maturity and the physical development of newborns on primary hypertension has
      been recently underlined. AIM: The aim of the study was to estimate the
      importance of low birth weight (< 10 percentiles--2500 g), low birth length (< 10
      percentiles--50 cm), low Apgar score (< 4 points), prematurity (< 37 Hbd) in the
      developmental of hypertension in children. METHODS: The project was conducted
      retrospectively in a group of 197 children with primary hypertension (aged 15.4
      +/- 1.9) and 119 healthy children (aged 12.9 +/- 3.1) as the control group. The
      statistical analysis was performed with Epilnfo 6.0 procedures. RESULTS: Male
      sex, overweight and family history of hypertension increased the risk of
      hypertension in a statistically significant way and the adequate estimated odds
      ratios were: OR = 3.69 (95% CI: 2.20-6.19), OR = 22.76 (95% CI: 6.61-94.12), OR =
      21.87 (95% CI: 6.27-91.1). No influence of low birth weight, low birth length,
      low Apgar score and prematurity on primary hypertension was observed. CONCLUSION:
      The results suggest that the role of low birth weight, low birth length, low
      Apgar score and prematurity in the development of hypertension in children is
      arguable. It also suggests the necessity to conduct epidemiologic surveys in more
      frequent groups of children.

PMID- 17441374
TI  - [Leptin correlates with distribution of fatty tissue and plasma levels of
      insulin, testosterone and tumor necrosis factor alpha in perimenopausal women
      with increased testosterone level and central location of body fat].
AB  - AIM: The evaluation of the influence of testosterone and fat tissue distribution
      on the serum leptin levels in perimenopausal women. PATIENTS: 93 perimenopausal
      women without HRT (age: 51.0 +/- 8.8 yrs, FSH: 68.0 +/- 49.4 IU/l, estradiol:
      38.3 +/- 37.0 ng/1) were divided into group A - 63 women with serum testosterone
      level < 0.6 ng/ml and group B--30 women with serum testosterone > or = 0.6 ng/ml.
      Each group was later divided according to WHR into subgroup I (AI and BI) (WHR <
      0.8) and II (AII and BII) (WHR > or = 0.8). METHODS: Basic fasting serum levels
      of LH, FSH, PRL, estradiol, insulin, hGH, IGF-I, IGFBP-1, IGFBP-3, leptin,
      testosterone, DHEAS TNF-alpha and SHBG were measured by RIA kits. Total
      cholesterol, HDL and LDL cholesterol, as well as triglycerides plasma levels were
      measured. Statistical evaluation was carried out by ANOVA and linear regression.
      RESULTS: BMI, WHR and plasma DHEAS level were higher in group B vs. group A. The
      lowest hGH, HDL-cholesterol and the highest TNF-alpha levels were found in group
      BII. The relations leptin/BMI and leptin/body mass were found in each group. The
      inverse relation between leptin and IGFBP-1 was found in groups A and B. In group
      A the inverse relations leptin/HDL-cholesterol and leptin/ DHEAS were observed.
      In group B the direct leptin/testosterone and inverse leptin/IGF-I relations were
      found. In group AI the inverse leptin/DHEAS relation remained, while in group AII
      inverse leptin/HDL-cholesterol relation remained and reverse leptin/IGFBP-1
      relation was significant. The direct leptin/testosterone, leptin/WHR and inverse
      leptin/TNF-alpha links were observed in group BII. CONCLUSION: The serum leptin
      level was linked to WHR, serum testosterone, insulin, TNF-alpha levels only in
      groups of perimenopausal women with such cardiovascular risk factors as high WHR,
      overweight, high serum TNF-alpha and testosterone levels.

PMID- 17441375
TI  - [Correlation between serum homocysteine levels and selected atherosclerosis risk
      factors in children and adolescents with simple obesity].
AB  - Homocysteine is known as an independent risk factor of atherosclerosis. The aim
      of this study was assessment of serum homocysteine concentrations in obese
      children and evaluation of possible relationship between homocysteine and risk
      factors of atherosclerosis. 498 children with simple obesity were included into
      our study. There was a significant correlation between serum homocysteine levels
      and both traditional and new risk factors of atherosclerosis. The issues confirm
      a necessity of evaluation serum homocysteine levels of obese children in
      estimation of cardiovascular disease risk.

PMID- 17441376
TI  - [TNFalpha and sVCAM plasma levels during standard exercise test are higher in
      postmenopausal women with hypercholesterolemia].
AB  - AIM: The evaluation of serum ICAM, VCAM, endothelin-1 (Et-1), TNF-alpha and its
      soluble receptor levels and the secretion of nitric oxide in postmenopausal women
      with hypercholesterolemia. PATIENTS: 26 postmenopausal patients who neither
      received hormonal therapy nor cholesterol lowering treatment. Group A consisted
      of 16 women with high serum total cholesterol and group B of 10 women with normal
      cholesterol level. METHODS: Basic fasting serum FSH, 17beta-estradiol, as well as
      total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides levels were
      evaluated. Standard exercise test was carried out according to Bruce protocol.
      Blood samples were taken thrice (prior to, at peak exercise, 15th min of
      recovery) during the test to evaluate the serum levels of ICAM, VCAM, ET-1, TNF
      alpha and its soluble receptors as well as secretion of nitric oxide. RESULTS: In
      group A--sVCAM (660.0 +/- 106.4 mg/l versus 518.6 +/- 65.4 mg/l; p < 0.05) and
      TNF-alpha serum levels (2.2 +/- 1.0 ng/l versus 1.2 +/- 0.4 ng/l; p < 0.05) at
      peak exercise were higher in group A compared to group B. There was a tendency (p
      > 0.05) of higher ET-1 plasma levels in group A. CONCLUSION: Serum levels of
      adhesion molecules and inflammatory mediators were higher during physical
      exercise in postmenopausal women with atherosclerosis risk factors.

PMID- 17441377
TI  - [Plasma granulocyte-macrophage colony stimulating factor (GM-CSF) and activity of
      enzymes in granulocytes of breast cancer patients].
AB  - GM-CSF (granulocyte-macrophage colony stimulating fractor) is a hematopoietic
      growth factor. In vitro it stimulates the proliferation of myeloid progenitors
      and formation of granulocyte and macrophage colonies. It was found that GM-CSF in
      vitro also stimulates the phagocytic function of mature granulocytes. Indirect
      evidence of this might be the increase of the activity of granulocyte enzymes
      participating in phagocytosis. The aim of this study was to compare in vivo the
      level of GM-CSF in the plasma and activity of acid phosphatase (AcP), alkaline
      phosphatase (AP), peroxidase (MPO) and esterase in granulocytes of breast cancer
      patients. The activities of tested enzymes were measured by cytochemical methods
      in the blood of 14 patients before and 30 days after surgery (group A) and 15
      patients before and in the course (12 week) of chemotherapy (groupB) and in 10
      healthy subjects. GM-CSF concentration was measured in the plasma, using a
      sensitive sandwich ELISA. According to obtained results we can conclude that GM
      CSF concentration in cancer patients before and after surgery compared to the
      control group was increased. GM-CSF concentration in patients before and in the
      course of chemotherapy was increased compared to the control group and patients
      before and after surgery. Enzyme activities participating in phagocytosis in
      cancer patients after surgery were increased compared to the enzyme activity in
      the control group. Enzyme activities in cancer patients in the course of
      chemotherapy were decreased when compared to the activities in the control group
      and when compared to the activities in cancer patients before and after surgery.
      The chemotherapy causes increase of GM-CSF concentration and enzyme activity.

PMID- 17441378
TI  - [Age-related muscle mass loss].
AB  - One of the signs of advancing age in humans is sarcopenia. The term is used to
      define the loss of muscle mass and strength that occurs with ageing. Sarcopenia
      contributes to the decreased capacity of independent living and increased amounts
      of traumas. Numbers of mechanisms are proposed as a cause of sarcopenia,
      including changes in protein metabolism, alterations in hormonal and neural
      functions, impaired regeneration after contraction-induced injuries,
      mitochondrial abnormalities, oxidative stress and apoptosis in skeletal muscle
      fibres. Further studies on the mechanisms leading to sarcopenia could provide the
      basis for prevention and establishment of therapeutic methods that would
      contribute to an increase in the standard of living among elderly people.

PMID- 17441379
TI  - [Ocular findings in patients with Steinert myotonic dystrophy].
AB  - The authors present one of many myotonic dystrophies: Steinert myotonic dystrophy
      (Steinert disease), which is a disease occuring seldom, and causing a lot of
      problems during the diagnostic and treatment process. Genetic factors, results of
      the histopathology tests, main clinical symptoms, particularly ophtalmic
      manifestation are described in this article.

PMID- 17441380
TI  - [Brachytherapy in the treatment of lung and tracheal cancer: current indications,
      methods, results].
AB  - Lack of improvement in treatment results of lung cancer leads to searching for
      new methods. One of the most distressing symptoms for lung cancer patients is
      airway obstruction due to the tumor, commonly resulting in dyspnea,
      postobstructive pneumonia, cough, or hemoptysis. Removal of endobronchial
      obstruction leads to quick improvement of clinical status and Quality of Life.
      Brachytherapy HDR of tracheal and lung cancer is a well-established method for
      the local treatment of patients with inoperable tumors of the tracheobronchial
      system. It seems that another promising treatment method of lung cancer is
      interstitial brachytherapy using permanent implants. The paper presents
      principles of brachytherapy, indications for this treatment and treatment results
      of tracheal and lung cancer. Indications for radical, palliative and interstitial
      treatment are discussed, respectively. Selected results of brachytherapy as an
      independent treatment and that combined with teletherapy, radical and, palliative
      are presented separately. Most commonly recognized complications are discussed
      which include: fatal pulmonary hemorrhage and fistula formation.

PMID- 17441381
TI  - [The latest diagnostical methods and therapy in melanoma].
AB  - Molecular biology, immunology, diagnostic and treatment of cutaneous melanoma
      have been analyzed on the basis of current literature due to the increasing
      frequency of this cancer. Due to the increasing frequency of melanoma it is
      crucial to detect early the malignant lesions on the basis of physical
      examination and noninvasive diagnostic methods (dermatoscopy, videodermatoscopy
      with total body photography). Histopathological examination is conclusive. In
      diagnostic imaging of early stage melanoma it is very important to evaluate the
      regional lymph node. In clinical practice, the cross-sectional imaging modalities
      including computed tomography (CT), ultrasound and magnetic resonance (MR) are
      widely used to assess lymph nodes. Sentinel lymph node (SLN) biopsy is currenly a
      valuable and reliable diagnostic procedure for precise staging of patients with
      clinically no cutaneous melanoma. The presence of SLN metastases is the most
      important negative factor for clinical outcome in melanoma patients. Introduction
      of RT-PCR allowed to detect individual cancer cells in tested sample of blood or
      tissue. Surgical treatment is an essential therapeutic modality in patients with
      melanoma. Treatment of a primary melanoma involves local excision of the tumour
      with a margin of skin and subcutaneous tissue. The role of systemic therapy is
      still a matter of clinical trials. Today's systemic therapy modalities include
      the use of biological agents (e.g. interferon alfa and interleukin 2) and
      cytotoxic agents. The efficacy of different types of melanoma vaccines
      (antigenic, cellular, DNA, GMTV) has been analyzed in numerous clinical trials.
      Results of these trials are still unsatisfactory. Dendritic cells in melanoma
      therapy will be very important in the future. Dendritic cells are the most
      efficient stimulators of T lymphocyte response among professional antygen
      presenting cells (APC) and the only APC capable to prime naive T lymphocytes with
      the antygen. A response to weakly immunogenic and tolerogenic tumor antigens can
      be achived with the use of DC as APC. This review represents an attempt to
      discuss current evidence on the place of adjuvant and palliative systemic therapy
      in melanoma.

PMID- 17441382
TI  - [The impact of periodontal infection on systemic inflammatory process and
      atherosclerosis].
AB  - It is becoming increasingly clear that infections and chronic inflammatory
      conditions, such as periodontitis can be linked with atherosclerotic process.
      Periodontitis and atherosclerosis have many pathogenetic mechanisms in common.
      The objective of this based on current knowledge review is to present the
      putative mechanisms whereby periodontitis which is chronic and inflammatory in
      nature and initiated by microbial plaque can influence the atherosclerosis. Two
      main processes in particular are worthy of consideration and may provide the link
      between these two diseases. Induction of the chronic systemic inflammation has
      been proposed to be of pathogenetic relevance in the association of infection and
      atherosclerosis, and may rely in part on the endothelial toxicity of bacterial
      endotoxin and the action of proinflammatory cytokines (PGE-2, IL-1beta, TNF
      alpha). Another well-founded proatherogenetic property of infectious illness may
      be the induction of autoimmunity and autoagression. It has been suggested that
      humoral immune cross-reaction of the same antibodies to heat shock proteins
      (HSP), both bacterial mHSP65 and human endothelial HSP60 may play an important
      role in the process of vascular endothelial injury. Both of these mechanisms are
      believed to be a key event in the pathogenesis of artheriosclerosis.

PMID- 17441383
TI  - [N-3 polyunsaturated fatty acid in cardiovascular disease].
AB  - The role of polyunsaturated n-3 fatty acids in prevention of many diseases,
      especially cardiovascular diseases, is becoming more and more important. In the
      article most important, selected by the author, studies on their legitimacy of
      application in prevention of coronary heart disease, sudden death and general
      cardio-protection are presented.

PMID- 17441384
TI  - [Autoregulation of cerebral circulation: adaptation to hypertension and re
      adaptation in response to antihypertensive treatment].
AB  - In chronic hypertension, autoregulation of cerebral blood flow (CBF) is adapted
      to high blood pressure. Thus in untreated hypertensive patients, the
      autoregulation curve is shifted towards higher pressure. With antihypertensive
      treatment autoregulation curve may be shifted back to the normal position or
      shift upward to the beneficially higher level of CBF. The effect of various
      antihypertensive drugs on CBF has been discussed.

PMID- 17441385
TI  - [Moyamoya disease as a cause of ischemic cerebral stroke in young people].
AB  - 35-year old patient was admitted to the Department of Neurology, Medical
      University of Bialystok because of paresis of his left upper limb, progressing
      over last 10 months and right facial nerve paresis, which started a month ago.
      During neurological examination he presented with right facial and arm paresis,
      dysarthric speech, obesity and hypertension. The patient was previously
      hospitalized in regional hospital, where a lumbar puncture was done revealing
      normal composition of cerebrospinal fluid. His brain CT revealed bilateral
      hypodensive areas in frontal and parietal regions of vasogenic character. Doppler
      ultrasound showed significant slowing of blood flow velocity in both internal
      carotid arteries. Brain angiography presented with very weak contrast filling of
      intracranial branches of carotid and vertebral arteries and showed stenosis at
      the terminal portion of the internal carotid arteries and at the proximal portion
      of the anterior and middle cerebral arteries. The patient had transthoracic and
      transesophageal echocardiography, Holter ECG, lab tests (routine lab tests plus
      coagulation system evaluation with C protein resistance test, anticardiolipne
      antibodies, antinuclear antibodies, anticytoplasmatic antibodies and thyroid
      hormones) checked--all tests were within normal range. Based on cerebral
      angiography and clinical symptoms, after excluding any other reasons of cerebral
      ischemia, the patient was diagnosed with moyamoya disease and arterial
      hypertension. The patient was treated pharmacologically with improvement-
      regression of face assymetry and dysarthria and diminishing of his right arm
      paresis. The authors of this paper pay attention to moyamoya disease as a rare
      reason of ischemic strokes in the young in our geographic region. They remind
      moyamoya disease diagnostic criteria, its etiology and treatment.

PMID- 17441386
TI  - [Focal fatty change (FFC) imitating liver malignancy. Own cases and review of
      literature].
AB  - Focal fatty change (FFC) may occur in the form of a single or numerous nodules of
      different size, located in the liver with otherwise normal structure. These
      changes, especially when they are large and single, pose an important diagnostic
      problem as their clinical and radiological picture may imitate malignancy. In the
      paper we report two cases of large hepatic tumors (12 cm and 8 cm) in patients,
      who had no factors predisposing to fatty liver changes (such as alcohol abuse,
      drugs, obesity, hormone disturbances, impaired blood flow through the liver or
      metabolic disturbances). In microscopic examinations the nodules were diagnosed
      as foci of large-droplet hepatocellular steatosis. Apart from these changes the
      liver was normal. CONCLUSION: FFC belongs to a group of pseudotumor changes. It
      occurs in rare cases and should be distinguished from diffuse changes observed
      frequently. In the differential diagnosis, the following must also be considered:
      primary hepatocellular tumors with fatty change, FNH with fatty change,
      mesenchymal tumors containing adipose tissue, fatty macro-regenerative nodule,
      adipocytic pseudotumor of the Glisson's capsule.

PMID- 17441387
TI  - [Gastric Crohn's disease as a cause of gastrointestinal bleeding after
      gastroscopy--diagnostic difficulties].
AB  - Crohn's disease is a chronic, idiopathic inflammatory bowel disease localized
      most commonly in the terminal ileum, but it may involve any site of the
      gastrointestinal tract. Stomach location is extremely rare. Usually this process
      is confused by the presence of fistulas and intraabdominal abscesses in the
      typical emplacement, which are the consequences of penetration of the
      inflammatory process through the whole thickness of the large intestine's wall.
      In the case of ithe upper part of the gastro-intestinal tract location (commonly
      distal part of stomach or proximal of duodenum) bleeding is the most dangerous
      complication. In the diagnostics of this disease the combination of endoscopy and
      immunobiochemical tests of taking fragments has the basic importance.
      Pharmacological immunosupression with protection of the stomach mucosa is still
      the treatment's method of choice. We report the case of isolated gastroduodenal
      Crohn's disease of the stomach complicated with bleeding.

PMID- 17441389
TI  - [Granulocytic sarcoma with late transformation into acute myeloblastic leukemia-
      case report].
AB  - Case presentation of a 28-year-old patient with acute myeloblastic leukemia (FAB
      AML-M4), who underwent surgery of an inguinal tumor a year before the diagnosis
      of leukemia was made. In retrospective assessment a diagnosis of granulocytic
      sarcoma was made. After induction and consolidation chemotherapy he achieved
      complete hematological remission and underwent matched unrelated donor bone
      marrow transplantation. After six months he relapsed. A repeated induction
      chemotherapy resulted in hematological remission. During maintenance therapy
      symptoms that appeared suggested an extramedullary relapse.

PMID- 17441388
TI  - [Primary adrenal lymphoma in incidentally discovered adrenal tumour].
AB  - The new imaging techniques used during the last several years: ultrasound,
      computed tomography and magnetic resonance imaging have improved detection of non
      functional adrenal tumours s.c. "incidentaloma". Incidence of adrenal
      incidentaloma is not very low. They are detected in about 0.35-4.36% CT
      examination. In most of cases incidentaloma are benign and gave no clinical
      signs; however primary adrenal cortex cancer and metastases of different cancers
      are not uncommon. The primary adrenal lymphoma is an extremely rare disease. The
      predominant group of patients are men over 50 years with other manifestations of
      non Hodgkin lymphoma. Most frequently both adrenal glands are affected and signs
      of adrenal insufficiency (despite weakness, fever and loss of weight) are
      present. In our paper we present a case of primary, unilateral lymphoma in a 19
      year old women. It was discovered as incidentaloma in ultrasound examination.
      Hormonal examinations were normal, but the tumour size was indication for surgery
      treatment. The diagnosis was made by histological examination and adjuvant
      chemotherapy was administrated.

PMID- 17441390
TI  - [Medical research and vulnerable subjects: unemployed people].
AB  - Although the importance of medical research for the diagnosis and treatment of
      human diseases is unquestionable, the use of human subjects, however, still
      presents a complex ethical problem. Moral difficulties occur in particular when
      the medical research deals with vulnerable subjects. Vulnerable individuals are
      defined as those who experience diminished actual autonomy. Among the groups
      which should be considered as being vulnerable are usually listed the following:
      children, pregnant women, mentally or emotionally disabled, physically disabled,
      homeless, and institutionalized people. This study addresses key concerns that
      gave rise to the question of whether unemployed people had to be recognized as
      vulnerable subjects. The term "vulnerability" was clarified and it was assumed
      that the "vulnerability" of medical research subjects' had to be understood as a
      form of continuum from potential, through the circumstantial, temporal, episodic,
      permanent to inevitable vulnerability. The conclusion was drawn that unemployed
      people were, at least, potentially vulnerable subjects. Research involving
      unemployed people presents important moral challenges to researchers and should
      be undertaken very carefully, following special ethical guidelines.

PMID- 17441391
TI  - Health promotion: whose responsibility is it?

PMID- 17441392
TI  - Lymphedema and implications for oncology nursing practice.
AB  - Lymphedema (LE) is described as chronic swelling caused by impairment in
      lymphatic system drainage. The cause of LE is either primary or secondary
      (Holcomb, 2006). The experience can be disturbing. Patients and healthcare
      providers often overlook the initial presentation because of subtle changes. With
      a basic understanding of LE, oncology nurses can monitor for the presence,
      educate about preventive measures, and assist in treatment of LE.

PMID- 17441393
TI  - Priapism in the oncology setting.
AB  - CASE STUDY: N.L. is a 20-year-old Caucasian man with no significant medical
      history. He presented to the hospital with a two-day history of feeling ill with
      intermittent nausea, vomiting, blurred vision, and headache. He also noted
      slurred speech and left-upper-quadrant fullness for almost a month.

PMID- 17441394
TI  - Diagnosing fungal infections in neutropenic patients.
AB  - Fungal infections are among the most serious complications in neutropenic
      patients. A major problem that has compromised management of fungal infections is
      healthcare professionals' inability to recognize the infections when they occur.
      No adequate diagnostic tools exist to detect many of the fungal infections. Early
      diagnosis of disseminated candidiasis is a challenge because only 35%-50% of
      neutropenic patients have positive blood cultures (Bodey, 1997), and radiologic
      tests have low specificity in that patient population. For example, a routine
      chest x-ray can be negative, yet a computed tomography (CT) scan of the chest can
      be positive for pneumonia the next day. Therefore, fungal infections often are
      advanced before diagnostic confirmation; thus, overall outcomes are poor. A great
      effort has been invested in developing serologic tests to detect circulating
      antigens of fungi.

PMID- 17441395
TI  - Seizures in people with cancer.
AB  - CASE STUDY: Ms. S is a 52-year-old woman who was diagnosed with infiltrating
      ductal breast carcinoma two years prior. She was treated with mastectomy followed
      by focal radiation and FAC (5-fluorouracil, adriamycin, and cyclophosphamide).
      One year ago, she began experiencing headaches. A magnetic resonance imaging scan
      with gadolinium revealed a 2 cm enhancing mass in the left temporal lobe, and she
      received whole-brain irradiation.

PMID- 17441396
TI  - Interventions for the management of weight and body composition changes in women
      with breast cancer.
AB  - Weight gain and body composition changes are common during the first year after
      breast cancer diagnosis. Women who are overweight or obese at the time of
      diagnosis or who gain weight following diagnosis are at higher risk for adverse
      clinical outcomes. Unhealthy weight conditions, compounded or caused by weight
      gain after diagnosis, are a considerable challenge for women with breast cancer
      during and after treatment. Despite the prevalence of weight gain in women with
      breast cancer as well as its adverse effects, little research has examined
      preventive and therapeutic interventions targeting reduction of weight and/or
      body fat. The purpose of this article is to update the state of knowledge on
      weight gain and body composition changes in women with breast cancer. Current
      evidence from weight intervention studies, including diet, exercise, and combined
      approaches for weight loss-or for prevention of weight gain-are reviewed. Along
      with published practice guidelines, the currently available information provides
      guidance for oncology nurses on the methods that can impact unhealthy weight
      conditions associated with breast cancer.

PMID- 17441397
TI  - Hematopoietic stem cell transplantation: implications for critical care nurses.
AB  - Hematopoietic stem cell transplantation (HSCT) is being used increasingly in the
      treatment of malignant and nonmalignant diseases. The treatment modality has been
      proven effective but is not without risks. Studies consistently have identified
      the need for advanced supportive care (e.g., multiple organ dysfunction,
      vasopressor use, mechanical ventilation) as a negative prognostic indicator in
      patients who have received HSCT. Among patients who have received HSCT, 15%-40%
      require critical care monitoring or advanced support. Nurses on intensive care
      units can positively impact outcomes for transplant recipients when they possess
      the specialized skills to recognize and promptly intervene when transplant
      related complications arise. This article will provide a basic overview of the
      HSCT process and outline the complications that may necessitate transfer to a
      higher level of care for specialized skills and equipment in the intensive care
      setting.

PMID- 17441398
TI  - Putting evidence into practice: evidence-based interventions to prevent, manage,
      and treat chemotherapy-induced nausea and vomiting.
AB  - Chemotherapy-induced nausea and vomiting (CINV) continues to have a considerable
      effect on the physical and psychological well-being of patients with cancer,
      despite significant advances in antiemetic drugs since the 1990s. This article
      reviews and summarizes past and current empirical evidence related to
      interventions for CINV. A resource that summarizes evidence-based interventions
      for CINV is critical for effective management of this distressing symptom.
      Pharmacologic and nonpharmacologic interventions are appraised. Finally, gaps in
      the literature and opportunities for research, education, and practice changes
      are discussed.

PMID- 17441399
TI  - Modeling a better way: navigating the healthcare system for patients with lung
      cancer.
AB  - The coordination of services for patients with suspected or newly diagnosed lung
      cancer produces improved patient outcomes, particularly in their quality of life.
      Evidence-based practice demonstrates improved outcomes from the multimodality
      therapies offered today, especially for patients with lung cancer; however,
      navigating through the healthcare system is especially challenging for patients.
      In developing the Multidisciplinary Lung Cancer Clinic at Frederick Memorial
      Hospital, navigation challenges in the healthcare system have been addressed.
      Patients are receptive and pleased with the approach, in which a nurse
      practitioner coordinates services and provides guidance and support for patients.
      The program offers benefits to patients with lung cancer in the community
      hospital setting. A similar program can be implemented in community cancer
      centers for patients with other diagnoses to improve outcomes and satisfaction
      with the healthcare system.

PMID- 17441400
TI  - Recognizing hyperviscosity syndrome in patients with Waldenstrom
      macroglobulinemia.
AB  - Hyperviscosity syndrome can develop in patients with plasma cell dyscrasias,
      particularly Waldenstrom macroglobulinemia (WM). Occurring in 10%-30% of patients
      with hyperviscosity syndrome, WM is an uncommon B-cell proliferative disorder
      characterized by bone marrow infiltration and production of monoclonal
      immunoglobulin M. The elevated blood viscosity in WM is the result of increased
      circulating serum immunoglobulin M. Because hyperviscosity syndrome can be
      lethal, it must be recognized and managed early. Hyperviscosity syndrome has a
      triad presentation: vision changes, neurologic abnormalities, and bleeding.
      Treatment includes hydration with diuresis, plasmapheresis, and control of the
      underlying disease. The current treatment for WM is chemotherapy (i.e.,
      alkylating agents and nucleoside analogs) and the monoclonal antibody rituximab.
      Although hyperviscosity syndrome is not one of the most common conditions, when
      it does occur, oncology nurses play a critical role in patients' assessment and
      care.

PMID- 17441401
TI  - Putting evidence into practice: evidence-based interventions for fatigue during
      and following cancer and its treatment.
AB  - Cancer-related fatigue has a significant impact on patients' physical and
      psychosocial functioning, symptom distress, and quality of life, yet it remains
      under-recognized and undertreated. The Oncology Nursing Society's Putting
      Evidence Into Practice initiative sought to improve patient outcomes relative to
      this important problem by critically examining and summarizing the evidence base
      for interventions to prevent and manage fatigue during and following treatment.
      This article critically reviews and summarizes the available empirical evidence
      regarding interventions for cancer-related fatigue. In addition to offering
      patients and clinicians a tool to facilitate effective management of the
      distressing symptom, this evidence-based review identifies gaps in knowledge and
      research opportunities.

PMID- 17441402
TI  - Obtaining family histories from patients with cancer.
AB  - Information obtained from family history data can provide valuable insight into
      the biologic and environmental etiologies of an individual's personal and family
      history of disease. The purpose of this article is to provide a brief
      introduction to cancer genetics and discuss ways to obtain accurate family
      histories in a time-efficient manner to identify families with a hereditary
      cancer syndrome. The focus is on gathering family history information, which
      should be a standard component of the initial intake for any patient and updated
      regularly to keep the information current.

PMID- 17441403
TI  - Overview of second-generation tyrosine kinase inhibitors for patients with
      imatinib-resistant chronic myelogenous leukemia.
AB  - Imatinib mesylate (Gleevec, Novartis Pharmaceuticals Corporation, East Hanover,
      NJ) has revolutionized the treatment of chronic myelogenous leukemia (CML) with
      marked improvement in survival in all three phases--chronic, accelerated, and
      blast. Most patients with CML now receive imatinib, which produces complete
      cytogenetic response in more than 80% of patients. About 10% of patients who
      initially respond to imatinib subsequently develop resistance. Mechanisms of
      imatinib resistance in CML include amplification, mutations, and additional
      chromosomal aberration. To date, more than 30 mutations have been identified in
      imatinib-resistant CML. Dasatinib and AMN107, second-generation tyrosine kinase
      inhibitors, are highly effective therapies for patients with CML experiencing
      imatinib resistance and mutation and offer new options for patients who do not
      achieve an optimal response to imatinib therapy. Studies found that dasatinib and
      AMN107 form tighter bonds, overcoming imatinib resistance and producing complete
      hematologic and cytogenetic remissions. Long-term observations are needed to
      determine the effectiveness of the treatment. Primary care providers need to
      follow patients receiving first- or second-generation tyrosine kinase inhibitors
      because unforeseen toxicity may surface, requiring accurate assessment,
      evaluation, and management. Oncology nurses will be actively involved in the
      symptom management of patients. Providing guidelines for symptom management and
      advanced knowledge of specific test results for monitoring CML may increase
      positive outcomes.

PMID- 17441404
TI  - National Institutes of Health Clinical Center hosts Clinical Investigator Student
      Trainee Forum.

PMID- 17441405
TI  - Fogarty International Center expands "Framework Programs in Global Health".

PMID- 17441406
TI  - National Library of Medicine sets $75 million in awards.

PMID- 17441407
TI  - Effects of multiple daily insulin injections on peripheral glucose disposal in
      Latin Americans with type 2 diabetes mellitus.
AB  - OBJECTIVE: To evaluate the effects of insulin in multiple daily injections (MDI)
      on peripheral glucose disposal in Latin American patients with type 2 diabetes.
      METHODS AND RESULTS: Ten Latin American patients (four men and six women) with
      type 2 diabetes between the ages of 32 and 45 years were evaluated. All women
      were premenopausal and had regular menstrual periods. A hyperinsulinemic
      euglycemic clamp procedure was performed at baseline and was repeated
      approximately 2 years after insulin monotherapy on MDI was initiated. Both
      genders had comparable baseline anthropometric and laboratory features, including
      a mean body mass index > 30 kg/m2 and percent body fat > 30%. Baseline percent
      hemoglobin A1c (HbA1c%) was 9.5 +/- 1.5%, and post-intervention HbA1c% was 7.0 +/
      1.2%. The peripheral glucose disposal rate at baseline was 4.5 +/- 2.2 mg/kg/min
      fat-free mass and at postintervention was 3.6 +/- 2.3 mg/kg/min fat-free mass.
      CONCLUSIONS: Despite a significant improvement in glycemic control, MDI did not
      seem to increase the insulin-mediated glucose disposal rate. Underlying obesity
      and increased percent body fat may have been the most counteracting factors on
      the potential improvement in insulin sensitivity expected with insulin
      monotherapy.

PMID- 17441408
TI  - Regulation of vascular proteoglycan synthesis by metabolic factors associated
      with diabetes.
AB  - BACKGROUND: Diabetes is associated with accelerated atherosclerosis, but the
      mechanisms responsible for this are not known. Proteoglycans have been shown to
      play a critical role in the initiation of atherosclerosis owing to their ability
      to bind and retain atherogenic lipoproteins in the artery wall. Proteoglycan
      structure and composition are altered in atherosclerotic lesions compared with
      adjacent normal regions of the artery wall, and this is exaggerated in diabetes.
      The purpose of this study was to determine if metabolic factors associated with
      diabetes lead to altered proteoglycan structure and composition. METHODS:
      Vascular smooth muscle cells, endothelial cells, and macrophages were exposed to
      normal (5.6 mmol/L) or high (25 mmol/L) glucose levels, various insulin and free
      fatty acid levels, and the cytokines transforming growth factor beta (TGF-beta1)
      and platelet-derived growth factor, alone or in combination, and proteoglycan
      synthesis was determined. RESULTS: Glucose concentrations, insulin, and free
      fatty acids did not alter proteoglycan synthesis, size, or relative distribution.
      The effect of TGF-beta to increase biglycan and versican synthesis, increase
      sulfate incorporation, and increase the size of the secreted proteoglycans was
      not altered by the ambient glucose level in the culture medium, nor did high
      glucose increase levels of active TGF-beta. CONCLUSION: Vascular proteoglycan
      synthesis is not affected by metabolic factors associated with diabetes. We
      suggest that elevated TGF-beta levels in diabetes are responsible for the altered
      proteoglycan synthesis observed in diabetes.

PMID- 17441409
TI  - Plasma cytokines, metabolic syndrome, and atherosclerosis in humans.
AB  - BACKGROUND: Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)
      integrate inflammatory and adipose signaling but also have direct vascular
      effects. We hypothesized that plasma levels of IL-6 and soluble tumor necrosis
      factor alpha receptor 2 (sol-TNFR2) would be related to coronary atherosclerosis
      beyond established risk factors and the metabolic syndrome. METHODS: We examined
      the association of IL-6 and sol-TNFR2 with metabolic syndrome, C-reactive protein
      (CRP), and coronary artery calcification (CAC) in 875 asymptomatic participants
      in the Study of Inherited Risk of Coronary Atherosclerosis. RESULTS: IL-6 levels
      were 56% higher (p < .001) and sol-TNFR2 levels 16% higher (p < .001) in subjects
      with metabolic syndrome compared with those without. Both cytokines were
      associated with CAC beyond age, gender, Framingham risk scores, family history,
      metabolic syndrome, and CRP (odds ratio and 95% confidence interval of higher CAC
      for 1 SD increase in log-transformed cytokine levels: 1.23 [1.06-1.43], p = .006
      for IL-6 and 1.15 [1.01-1.31], p = .04 for sol-TNFR2). In fact, cytokine levels
      were independently associated with CAC scores in the subgroup with metabolic
      syndrome and were additive to the homeostasis model assessment of insulin
      resistance in predicting CAC. CONCLUSIONS: Plasma IL-6 and sol-TNFR2 levels were
      independently associated with CAC, suggesting a role in integrating innate immune
      and adipose signaling in promoting atherosclerosis and cardiovascular risk.
      Measurement of their levels may facilitate cardiovascular risk prediction and
      targeting of therapeutic strategies.

PMID- 17441410
TI  - Uric acid homeostasis in the evaluation of diuretic-induced hyponatremia.
AB  - BACKGROUND: Diuretics are one of the most common causes of severe hyponatremia.
      The responsible pathogenetic mechanisms remain unclear. Serum uric acid
      concentration has been proposed as an index of differentiating between two
      pathophysiologic constructs of diuretic-induced hyponatremia-extracellular volume
      depletion and syndrome of inappropriate antidiuretic hormone secretion (SIADH)
      like state-but its discriminating value has not been verified in large series of
      patients. Here we attempt to illuminate the pathophysiology of diuretic-induced
      hyponatremia by focusing on uric acid homeostasis. Additionally, we analyze the
      epidemiology and clinical characteristics of the disorder. METHODS: We studied
      prospectively 158 adult patients with hyponatremia on admission to our internal
      medicine clinic. Here we report on those with diuretic-induced hyponatremia.
      RESULTS: Forty patients (13 male and 27 female) had diuretic-induced
      hyponatremia, rendering it the most common cause of the disorder (25.3%). These
      patients had lower mean ([Na+]) (121.2 +/- 7.2 vs 126.4 +/- 4.1 mEq/L, p = .0001)
      than the remaining hyponatremic patients. Patients with serum uric acid levels <
      4 mg/dL (n = 14) exhibited a biochemical profile consistent with a SIADH-like
      state, whereas patients with serum uric acid levels > or = 4 mg/d (n = 26) were
      consistent with extracellular volume depletion. CONCLUSIONS: Diuretics are the
      most common cause of community-developed hyponatremia. The serum uric acid level
      effectively discriminates between two biochemical profiles of diuretic-induced
      hyponatremia, one consistent with extracellular volume depletion and another that
      simulates SIADH.

PMID- 17441411
TI  - Patients page. Teeth whitening--basics for the patient.

PMID- 17441412
TI  - Oklahoma Dental Association. 1907-2007.

PMID- 17441413
TI  - Workers compensation: a business necessity.

PMID- 17441414
TI  - Evaluation of the antiinflammatory and clinical effects of sublingual
      immunotherapy with carbamylated allergoid in allergic asthma with or without
      rhinitis. A 12-month perspective randomized, controlled, trial.
AB  - BACKGROUND: The efficacy and safety of sublingual immunotherapy with carbamylated
      allergoid (allergoid SLIT) is well recognised. Yet, few data concerning its
      antiinflammatory effects on the respiratory airways are so far available. Thus we
      decided to evaluate whether it can reduce the allergic inflammation and improve
      the clinical symptoms in comparison to pharmacotherapy. METHODS: The study was
      perspective, controlled and randomised. It was conducted on 56 patients allergic
      to House Dust Mite with (n=36) or without Parietaria. Thirty-three of them were
      allocated to SLIT (22 M, 11 F mean age 15 years) and 22 (13 M, 10 F, mean age 21
      years) to pharmacotherapy They were followed-up for 1 year. Symptoms and drugs
      consumption were assessed by monthly diary cards. Bronchial reactivity was
      investigated at baseline and after a 12-month treatment, through a methacholine
      (MCh) test. An evaluation of the nasal eosinophils was also performed at the same
      times. RESULTS: There was a greater reduction of the mean symptom score (p <
      0.01) and drug consumption (p < 0.001) in the SLIT than in the control group. MCh
      PD20 increased only in the SLIT group (p < 0.0005) The reduction of nasal
      eosinophils was statistically greater (p < 0.05) only in the SLIT group.
      CONCLUSIONS: A 1-year SLIT reduces the allergic symptoms and the respiratory
      airways inflammation more than pharmacotherapy.

PMID- 17441415
TI  - GliSODin, a vegetal sod with gliadin, as preventative agent vs. atherosclerosis,
      as confirmed with carotid ultrasound-B imaging.
AB  - Prevention of cardiovascular disease should target high-risk subjects based on
      genetic/familial factors, blood chemistry, blood pressure, body mass index (BMI),
      and a history of/or current cigarette smoking. We selected active adults (n=76)
      aged 30-60 and investigated these risk factors, in order to recommend preventive
      measures. Another interesting variable is the preclinical status or atheroma of
      the arterial (carotid) wall or lumen. We also investigated the presence of
      oxidative stress in, and the anti-oxidant status of these subjects. We studied
      the anti-oxidative efficacy of superoxide dismutase (SOD) and variations of
      malondialdehyde (MDA). Supplementation with GliSODin, a vegetal SOD associated
      with gliadin, was effective in controlling the thickness of the carotid artery
      intima and media layers as measured by ultrasonography-B. We could demonstrate
      the preventive efficacy of GliSODin at a preclinical stage in subjects with risk
      factors of cardiovascular disease.

PMID- 17441416
TI  - Survey of prick test, total and specific age during food allergy in children.
AB  - AIM: To analyze the results of a systematic survey of biological tests in a
      symptomatic pediatric population consulting for the exploration of a possible
      food allergy. PATIENTS AND METHODS: 406 children included in this study, mean age
      3.3+3.2 years (2 months-16 years), 159 girls and 247 boys, had cutaneous tests
      (Stallergenes, Paris, France), assaying of total and specific IgE, and RAST Fx5
      (Pharmacia & Upjohn Diagnostics AB, Uppsala, Sweden). Those children suffering
      from eczema (34.9%), digestive disorders (26.1%), ORL and pulmonary (8.3%),
      anaphylactic choc (3.4%) or mixed symptoms (27.3%). RESULTS: The overall
      positivity of cutaneous tests, all confused age periods, was 34.1% with the
      following order: egg white (52%, p < 0.05 vs. other food), peanut (46%), egg yolk
      (42%), fish (34%), wheat (33%), soy (32%), cow's milk (24%) and rice (17%). It
      decreased significantly with age only for the egg white, 61% (0-1 year) and 68%
      (1-2 years) vs 31% (> 6 years), p < 0.05. The positivity of cutaneous tests for
      egg and peanut was more frequent with eczema than with digestive manifestations
      (64% vs. 44%, 57.6% vs. 34% and 56% vs. 38.7%, p < 0.05). The title of total IgE
      increased with age, r 0.5 p 0.001. The positivity of specific food IgE was more
      frequent at 4-6 years (68%) than at 0-1 year (36%), p < 0.05. It revealed, all
      confused age periods, the following order: egg white (74%) and peanut (64%), p <
      0.05 vs. other food, cow's milk (59%), wheat (55%), soy (45%) and fish (24%). The
      number of high specific food IgE titers was significantly higher than the number
      of positive cutaneous tests by order of frequency; egg white, peanut, cow's milk,
      wheat and soy, p < 0.05; the reverse was observed for fish, p < 0.05. Percentage
      of subjects combining a high title of specific food IgE and a positive cutaneous
      test for egg white (39.4%) was significantly higher than the percentage of those
      combining a high RAST Fx5 title and a positive cutaneous test for at least one of
      6 corresponding foods (25.2%), p < 0.05. CONCLUSION: The positivity of different
      food cutaneous tests, the rate of total and specific IgE titers and the agreement
      of the results varied according to age, food and symptoms.

PMID- 17441417
TI  - The pattern and genetics of pediatric extrinsic asthma risk factors in polluted
      environment.
AB  - AIM: The aim of the present study is to determine the effect of polluted
      environment on extrinsic of asthma and allergic diseases among school children.
      DESIGN: This is case and control study. SETTING: The study was carried out among
      school children living and attending the school in industrial and residential
      area during the period of October 2004 and June 2005. SUBJECTS: The study based
      on age, sex, and ethnicity of 716 cases (with asthma) and 716 controls (without
      asthma) school children living in both urban and in industrial polluted with oil
      refinery and chemical pollutant. METHODS: The International study of asthma and
      allergies in childhood (ISAAC) and some additional questionnaires were used to
      collect the data of the school children. The questionnaire included information
      about: socio-demographic characteristics; respiratory symptoms; associated
      respiratory illness; family history of allergic diseases among first-degree
      relatives of asthmatic children; behavioural factors which could be additive to
      asthma. Univariate and multivariate statistical analyses were performed. RESULTS:
      The proportion of children in the asthmatic group who reported symptoms was
      significantly higher than in non-asthmatic group (<0.0001). The asthmatic group
      reported that 47.5% morning time breathlessness, shortness of breath (61.4%),
      wheeze after exercise (65.4%), phlegm (45.3%) and chronic cough (42.2%). Male
      asthmatics had a average age at onset of symptoms of 6.9% (+/-4.8%) years
      compared with female asthmatics who had higher age at onset of symptoms, 7.6 (+/
      5.9). Male asthmatics also had longer duration of symptoms (7.5 +/- 4.9 in males
      and 6.4 +/- 4.6 years in females). Significantly odds ratios were found higher in
      asthmatic compared to controls for pneumonia, bronchitis, atopy (allergic
      rhinitis and atopic dermatitis), sinusitis, croup, parental asthmas, parental
      atopy including parental allergic rhinitis, atopic dermatitis and parental
      smoking (p < 0.0001). The logistic regression model showed that shortness of
      breath, bronchitis, pneumonia, sinusitis, parental asthma, allergic rhinitis,
      atopic dermatitis, croup, pets ownership and parental smoking were significant
      risk factors for asthma CONCLUSION: The present study provides some evidence that
      exposure to outdoor air pollutants increases the risk of childhood asthma and
      allergic diseases in school children. The results are consistent with the
      hypothesis that long term exposure to NOx and CO levels suggests that emissions
      from photochemical air pollution and oil refinery contributes to adverse health
      effects in Qatar.

PMID- 17441418
TI  - Improved efficacy of aerosol delivery to distal airways in pediatric subjects
      using a new spacer mouth-mask.
AB  - Aerosol nebulization is and most effective ways of treating airway diseases
      especially in children. Failure of inhaled asthma treatment is mainly due to
      inadequate deposition of drugs in the peripheral area of the lungs. The aim of
      this study was to compare the efficacy of a traditional mask and that of a new
      spacer mouth-mask (Nebula, Markos Mefar, Italy) when used with a jet nebulizer,
      by measuring aerosol deposition in the lungs, oropharynx, upper airways, and
      gastrointestinal tract. Twelve children without respiratory disease aged between
      8 and 13 years were included in the study. Aerosol inhalation was performed using
      a jet nebulizer with 2 mL of saline solution containing 20 Mci of Tc99m-DTPA. The
      first group initially performed aerosol inhalation using a traditional facemask
      and then, one week later, using the new spacer mouth-mask. The second group
      performed aerosol inhalation using the new spacer mouth-mask first and then, one
      week later, using a traditional mask. Scintigraphic ventilation images were then
      obtained, and aerosol deposition in the trachea, oropharynx, lungs and stomach
      was measured. In the first group, the radioaerosol deposition in the peripheral
      lung area using the new spacer mouth-mask was greater 97.8 +/- 7.0 vs. 68.5 +/-
      7.9 (p = 0.04). On the other hand, the oropharyngeal radioaerosol deposition was
      greater using the traditional mask: 50.2 +/- 5.2 vs 20.3 +/- 11.8 (p = 0.028).
      Similarly, in the second group the peripheral lung deposition was greater and the
      oropharyngeal deposition was less using the new spacer mouth-mask: 97.3 +/- 9.4
      vs. 70.2 +/- 11.2 and 20.7 +/- 8.9 vs. 46.3 +/- 16.8 (p = 0.028 and 0.046
      respectively). In conclusion, the new design of the spacer mouth-mask allows
      greater aerosol deposition in the peripheral lung area and less in other parts
      such as the oropharyngeal area, the central airways and the stomach.

PMID- 17441419
TI  - [The study of resilience of oral pharyngeal wall in patients with obstructive
      sleep apnea hypopnea syndrome applied with multiple detector-row spiral CT].
AB  - OBJECTIVE: To explore the resilience of oral pharyngeal wall in patients with
      obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD: Applied with multiple
      detector-row spiral CT, 24 patients with OSAHS and 10 volunteers were scanned
      from nasopharynx to hypopharynx under the normal breathing state and the
      breathing state of Muller maneuver. The relevant dimensions of area and thickness
      of retropharyngeal soft tissue were measured in some level in imagings including
      the soft palatal level, the lingual level and the epiglottic level, then the
      resilience of these levels were calculated according to the above data. RESULT:
      The values of resilience of oral pharyngeal wall were larger in patients with
      OSAHS than those in the volunteers. The difference of the values of resilience in
      soft palatal level and lingual level was statistically significant (P < 0.01).
      The values of thickness of retropharyngeal soft tissue in the soft palatal level,
      the lingual level and the epiglottic level were respectively (7.5 +/- 2.2) mm,
      (4.8 +/- 1.3) mm, and (2.3 +/- 0.2) mm. There was a significant difference in the
      thickness in soft palatal level between the patients with OSAHS and the
      volunteers (P < 0.01). The indexes of Pearson correlation of between the
      thickness of retropharyngeal soft tissue and the resilience of the pharyngeal
      wall decreased from the soft palatal level to the epiglottic level in these two
      groups. Only the value of correlation coefficient in the soft palatal level was
      statistically significant in patients with OSAHS. CONCLUSION: The study suggested
      that the resilience of pharyngeal wall could be quantitated by applying with
      multiple detector-row spiral CT. The resilience of oral pharyngeal and its
      correlation with thickness of retropharyngeal soft tissue may be the highest in
      soft palatal level.

PMID- 17441420
TI  - [Evaluation of effectiveness of advanced tonsillar carcinoma by different
      treatment].
AB  - OBJECTIVE: To evaluate the treatment of advanced tonsillar carcinoma by
      radiotherapy plus salvage surgery (R+S) or surgery coupling with postoperative
      radiotherapy (S+R). METHOD: Clinical data of 48 patients with advanced tonsillar
      carcinoma who were treated in The 2nd Affiliated Hospital of Sun Yat-sen
      University from June 1996 to June 2004 was retrospectively analyzed. The patients
      were divided into R+S group (group A, 21 cases) and S+R group (group B, 27
      cases). Treatment outcomes were compared between these two groups. The QOL
      (quality of life) scale of Washington University (UW-QOL) was used to investigate
      the patient's quality of life. RESULT: The 5-year survival rates were 42.9% in
      group A and 45.8% in group B, there was no significant statistical difference
      between the two groups (P < 0.05). Both the two treatment modalities could reduce
      the QOL in some degree. The average QOL score of 46 patients was 661.00 +/- 98.52
      , group A was 696.09 + 90.70, while group B was 631.52 +/- 96.74, there was a
      significant statistical difference between the two groups (P < 0.05). CONCLUSION:
      The two treatment modalities reached similar survivals. However, compared with
      the S+R, some patients who accepted treatment of R+S could avoid composite
      resection, reduce functional lesion and improve the QOL.

PMID- 17441421
TI  - [Clinical significance and expression of FLIP and PTEN protein in laryngeal
      squamous cell carcinoma].
AB  - OBJECTIVE: To investigate the expression of FLIP and PTEN in laryngeal Squamous
      cell carcinoma (LSCC), and the relationship between FLIP and PTEN. METHOD: The
      protein expression of FLIP and PTEN were examined by using immunohistochemical
      method in 45 cases of LSCC and 15 cases of para-carcinoma tissues. RESULT: FLIP
      protein positive expressive rate in the laryngeal squamous cell carcinoma cases
      (77.8%) was higher than that in the para-carcinoma tissues cases (33.3%, P <
      0.05). The protein expression of FLIP was correlated with cervical lymph node
      metastasis, clinical stage and prognosis. On the other hand, PTEN positive
      expressive rate in the laryngeal squamous cell carcinoma (65.0%) was higher than
      that in the para-carcinoma tissues (0%, P < 0.01). The protein expression of PTEN
      was associated with tumor differentiation grade, clinical stage, cervical lymph
      node metastasis and prognosis. There was a negative relationship between the
      expression of FLIP and PTEN in LSCC. CONCLUSION: The protein expression of FLIP
      may be an important prognostic marker for LSCC. The protein expression of PTEN
      was correlated with clinical stage, tumor differentiation grade, and cervical
      lymph node metastasis . Consequently, it could be used as a valuable marker for
      the prognosis of LSCC.

PMID- 17441422
TI  - [Application of coblation assisted upper-airway procedure to obstructive sleep
      apnea-hypopnea syndrome].
AB  - OBJECTIVE: To investigate the efficacy and the value of CAUP in treatment of
      OSAHS. METHOD: CAUP and the dissection of palatopharyngeus muscle were performed
      by RFVTR . One hundred and sixty-eight patients with OSAHS treated by CAUP from
      July 2001 to July 2004 were summarized. Among them, 52 patients were analyzed by
      PSG after 1 year of the operation. RESULT: All the operative procedure were
      carried out smoothly with excellent patient tolerance. Post-operation
      complications were foreign body feeling in oral cavity. No velopalatal
      insufficiency occurred. The efficient rate was 94.2% after 1 year of the
      operation according to the PSG results. CONCLUSION: CAUP is a simple,
      safe,repeatable and acceptable surgical procedure and it was developing with
      excellent value in the treatment of OSAHS on the basic of accurate X-ray imaging.

PMID- 17441423
TI  - [Transcranial endoscopic excision of glossopharyngeal nerve to treat
      glossopharyngeal neuralgia].
AB  - OBJECTIVE: To introduce a new transcranial endoscopic approach of
      glossopharyngeal neurotomy to treat glossopharyngeal neuralgia. METHOD: The
      clinical data, the operative technique, the operative effect and the result of
      follow-up of two patients were presented. Through reviewing pertinent literature,
      we discussed the therapeutic advancement of glossopharyngeal neuralgia and the
      preponderance of transcranial endoscopic approach of glossopharyngeal neurotomy.
      RESULT: The two patients both have satisfied outcomes and remained free of
      disease after surgical treatment. The endoscopic surgery has many significant
      advantages, such as rigorous operation, little injury, precise therapeutic
      effect, few complication, and so on. CONCLUSION: Transcranial endoscopic approach
      of glossopharyngeal neurotomy is an ideal method to treat glossopharyngeal
      neuralgia.

PMID- 17441424
TI  - [Expression of STAT3 and P-STAT3 in laryngeal carcinoma and its clinical
      significance].
AB  - OBJECTIVE: To investigate the expression of STAT3 and P-STAT3 and the
      relationship between P-STAT3 and various clinical pathological characteristics in
      human laryngeal carcinoma. METHOD: The expression of STAT3 and its activated form
      P-STAT3 in tumor tissues from 50 radically resected specimens of laryngeal
      carcinoma and 10 normal laryngeal tissues was detected by immunohistochemical
      staining. RESULT: The rate of protein expression of STAT3 and P-STAT3 in
      laryngeal carcinoma were 36/50 (72.0%) and 29/50 (58.0%) respectively, which were
      significantly higher than that in normal group (P < 0.01). The positive rate of P
      STAT3 was closely related to the clinical stage and lymph node metastasis (P <
      0.05). The expression STAT3 in laryngeal carcinoma was located in the cytoplasm
      of carcinoma cells, while P-STAT3 was located in the cell nucleus. CONCLUSION:
      STAT3 and PSTAT3 were overexpressed in human laryngeal carcinoma. Activation of
      STAT3 was significantly related to the clinical stage and lymph node metastasis.
      The expression of STAT3 can be used as a significant parameter in predicting the
      biological behaviour of laryngeal carcinoma.

PMID- 17441425
TI  - [MSCT diagnostic value to foreign body and stenosis in trachea and bronchus of
      children].
AB  - OBJECTIVE: To evaluate MSCT diagnostic value in children with foreign body and
      stenosis in trachea and bronchus. MATERIALS AND METHOD: MSCT scan was done in 18
      children suspected foreign body and stenosis in trachea and bronchus.
      Postprocessed (included Minp and MPR) were done after the axial images were
      obtained. All of 18 cases underwent conventional BFS. RESULT: Fifteen cases were
      shown with foreign body through MSCT scan. In addition, total amount of foreign
      body reached 21 pieces; The CT value in one case was 278 HU, in the others were
      from--10.6 HU to 31 HU; Stenosis in trachea and bronchus was found in 2 cases;
      Stenosis in laryngeal cavity after foreign body removing in one case. Foreign
      body and stenosis in trachea and bronchus were shown better in MPR and Minp
      images. MSCT images were not only conformed to BFS completely, but also showing
      foreign body in segmental bronchus more accurately. CONCLUSION: MSCT scanning
      could show direct and indirect signs of the foreign body and stenosis in trachea
      and bronchus accurately, and determine the nature of foreign body. It can act as
      a primary examination.

PMID- 17441426
TI  - [Clinical analysis of the laryngeal injury].
AB  - OBJECTIVE: To explore the management of the laryngeal injury. METHOD: The forty
      five patients of laryngeal injury had been rescued. Twenty eight patients were
      treated with the tracheotomy and twenty four patients of them were treated with
      the laryngoplasty. RESULT: All the patients were survived. Tracheostomy tube of
      twenty eight patients was taken away without the cicatricial structure of larynx.
      CONCLUSION: With the reasonable management after the laryngeal injury, the injury
      could be cured in time without complications.

PMID- 17441427
TI  - [Expression of connective tissue growth factor (CTGF), osteopontin (OPN) and
      clinical significances in the laryngeal squamous cell carcinoma tissues].
AB  - OBJECTIVE: To study the expressions of CTGF and OPN and detect their clinical
      value and correlation in the laryngeal squamous cell carcinoma tissues and
      paracancerous tissues. METHOD: SP immunohistochemical method was used for the
      assays of CTGF and OPN on the routinely paraffin-embedded sections of surgical
      operated specimens of 41 cases with laryngeal squamous cell carcinoma and 20 ones
      with paracancerous tissues. RESULT: The positive rate of CTGF and the score were
      significantly lower in cancer tissues than those in paracancerous tissues (61.0%
      vs 90.0%, P < 0.05; 2.41 +/- 1.60 vs 4.24 +/- 1.42, P < 0.01), but those of OPN
      were opposite (61.0% vs 15.0%, P < 0.01; 3. 10 +/- 1.63 vs 1.12 +/- 0.84, P <
      0.01). The positive rates and scores of CTGF were significantly higher in the
      cases without-metastasis of lymph node and clinical stage T1 than those in the
      ones with-metastasis of lymph node and clinical stage T3 (P < 0.01) . The
      positive rates and scores of OPN were significantly lower in the cases without
      metastasis of lymph node, clinical stage T1 and histological grade I those that
      in the ones with-metastasis of lymph node, Clinical stage T3 and histological
      grade III (P < 0.01). The closely negative correlation was found between the
      score of CTGF and that of OPN. CONCLUSION: The expression of CTGF and/or OPN
      might be important biological markers in reflecting the progression, biological
      behaviors, metastatic potential and prognosis of the laryngeal squamous cell
      carcinoma.

PMID- 17441428
TI  - [Preservation of laryngeal function in treatment of pyriform sinus carcinoma].
AB  - OBJECTIVE: To study the treatment outcome of laryngeal function sparing of
      pharyngectomy in pyriform sinus carcinoma. METHOD: Fourty-two cases with pyriform
      sinus cancer in laryngeal function sparing surgery were collected from 1989 to
      1999. The method of operation, the complication and surviving rate were analyzed.
      RESULT: The decannulation rate was 61.9% (26/42) . The rate of complication was
      31.0% (13/42), the 3 years and 5 years' survival rates were 76.1% and 66.6%
      respectively. CONCLUSION: Laryngeal function preserving surgery in pyriform sinus
      cancer could performed for stage T1, T2 and part of stage II, IV patients, and
      this surgery can improve the patients, life quality.

PMID- 17441429
TI  - [Effect of anteroposterior cricoid split on cartilage growth in rabbits].
AB  - OBJECTIVE: To investigate the effect of the anteroposterior cricoid split on
      cartilage growth. METHOD: The rabbits were killed 8 months after the surgery of
      anteroposterior cricoid split. The larynxes were harvested and the cross
      sectional area of the cricoid cartilage were calculated. RESULT: There was no
      significant difference in the cross-sectional area of the cricoid cartilage of
      these three groups. CONCLUSION: The anteroposterior cricoid split might have no
      adverse effect on subsequent growth of cricoid cartilage.

PMID- 17441430
TI  - [Expression of PML in carcinogenesis of laryngocarcinoma and nasopharyngeal
      carcinoma].
AB  - OBJECTIVE: To explore the significance of PML expression in carcinogenesis of
      laryngocarcinoma and nasopharyngeal carcinoma. METHOD: The PML expression in 56
      laryngocarcinoma tissues and 34 nasopharyngeal carcinoma tissues were examined by
      immunohistochemistry. Moreover, the relationship between the PML expression, with
      the pathologic grade,T stage and lymph node metastasis was analyzed. RESULT: The
      PML expression decreased with the ascending of pathological tumor grade (P <
      0.05) and with the increasing of T grade of tumor (P < 0.05). The expression of
      PML in nasopharyngeal carcinoma was lower than that in carcinoma of larynx (P <
      0.05). However, either in laryngocarcinoma or in nasopharyngeal carcinoma, there
      was no statistical difference on PML expression between with and without lymph
      node metastasis in laryngo carcinoma tissues and nasopharyngeal carcinoma
      tissues. CONCLUSION: The close relationship between PML expression and the
      malignant parameters such as pathological grade and T grade of laryngocarcinoma
      and nasopharyngeal carcinoma, indicated that PML may play a role in cancer
      repression but not in cancer metastasis.

PMID- 17441431
TI  - Didymium-like myxogastrids (class Mycetozoa) as endocommensals of sea urchins
      (Sphaerechinus granularis).
AB  - This paper sums up the results of light microscopical, ultrastructural and
      molecular studies of five strains of amoeboid organisms isolated as
      endocommensals from coelomic fluid of sea urchins, Sphaerechinus granularis
      (Lamarck), collected in the Adriatic Sea. The organisms are reported as Didymium
      like myxogastrids. Of the life-cycle stages, the attached amoeboids, flagellated
      trophozoites, cysts and biflagellated swarmers are described. Formation of
      fruiting bodies was not observed. Although phylogenetic analyses of SSU rDNA
      sequences indicated a close relationship with Hyperamoeba dachnaya, our sea
      urchin strains have not been assigned to the genus Hyperamoeba Alexeieff, 1923.
      The presence of either one or two flagella reported in phylogenetically closely
      related organisms and mutually distant phylogenetic positions of strains declared
      as representatives of the genus Hyperamoeba justify our approach. Data obtained
      in this study may be useful in future analyses of relationships of the genera
      Didymium, Hyperamoeba, Physarum and Pseudodidymium as well as in higher-order
      phylogeny of Myxogastrea.

PMID- 17441432
TI  - Endogenous development of Hemolivia mauritanica (Apicomplexa: Adeleina:
      Haemogregarinidae) in the marginated tortoise Testudo marginata (Reptilia:
      Testudinidae): evidence from experimental infection.
AB  - Six young tortoises Testudo marginata Schoepff, 1792 were experimentally infected
      with Hemolivia mauritanica (Sergent et Sergent, 1904). The prepatent period
      ranged from 6 to 8 weeks. Young, smaller, club-like forms (6-9 x 3-6 Am) of
      gametocytes appeared in the peripheral blood first, whereas mature, elongated,
      cylindrical forms (9-12 x 5-7 Am) were detected after 1-2 weeks and predominated
      during later patency. Three of the infected tortoises were euthanized and
      dissected to study the endogenous stages. Meronts occurred in the cells of the
      reticulo-endothelial system and in the erythrocytes; these were observed mostly
      in parenchymatous organs. Mature forms measured 14.2 x 9.3 microm and contained 7
      12 merozoites. Cysts with two (exceptionally one) cystozoites were also found
      predominantly in parenchymatous organs and measured 14.8 x 7.9 microm.
      Pathological changes attributable to Hemolivia were mild and limited to liver and
      kidneys. The role of individual developmental stages of haemogregarines is
      discussed with respect to evolution of heteroxenous life cycle and long-term
      persistence of parasites in their intermediate hosts.

PMID- 17441433
TI  - Monostephanostomum nolani sp. n. and M. krusei Reimer, 1983 (Digenea:
      Acanthocolpidae) from carangid fishes from coral reef waters off Australia.
AB  - Monostephanostonum nolani sp. n. is described from Carangoides plagiotaenia
      Bleeker, off Lizard Island, Great Barrier Reef, Queensland, Australia. It differs
      from all other species in the genus except M. manteri Kruse, 1979 in that the
      vitellarium reaches into the forebody. It differs from M. manteri in the ventral
      hiatus in the circum-oral spine row, the extent of the vitellarium in the
      forebody, where it is not confluent, its elongate pharynx and its smaller eggs.
      Monostephanostoinum krusei Reimer, 1983 is redescribed from Pseudocaranx dentex
      (Bloch et Schneider) from Ningaloo Reef off Western Australia. It is considered
      similar to M. nolani, differing in the vitellarium being restricted to the
      hindbody, but sharing with M. nolani an unusual arrangement of small body-spines
      on the antero-ventral surface. It is also morphologically very similar to
      Monostephanostomum roytmani (Parukhin, 1974), which apparently lacks the
      diminutive antero-ventral body-spines. A key to eight recognized species in the
      genus is presented.

PMID- 17441434
TI  - Polylabris lingaoensis sp. n. and Polylabris cf. mamaevi Ogawa et Egusa, 1980
      (Monogenoidea: Microcotylidae) from perciform fishes in the Gulf of Tonkin, South
      China Sea.
AB  - Polylabris lingaoensis sp. n. is described from the gills of the bald glassy,
      Ambassis gymnocephalus (Chandidae), from the Gulf of Tonkin (South China Sea),
      near Lingao, Hainan Province, China. The new species is characterized by a
      midventral vaginal pore, comparatively few (5-7) testes, and 2 parallel rows each
      comprised of 30-43 microcotylid clamps in the haptor. Polylabris lingaoensis is
      the only member of the genus known to parasitize a chandid host. Polylabris cf.
      mamaevi is described from the gills of the mottled spinefoot, Siganus fuscescens
      (Siganidae), from the South China Sea, which represents new host and locality
      records for the helminth. The gill parasites from S. fuscescens are tentatively
      assigned to P. mamaevi pending new collections and restudy of microcotylid
      species from siganid fishes.

PMID- 17441435
TI  - Invalidity of three Palaearctic species of Triaenophorus tapeworms (Cestoda:
      Pseudophyllidea): evidence from morphometric analysis of scolex hooks.
AB  - A comparative study of the scolex hook morphology of five species of tapeworms of
      the genus Triaenophorus Rudolphi, 1793 (Cestoda: Pseudophyllidea), parasites of
      pikes (Esox lucius L. and E. reichertii Dybowski) in the Palaearctic Region, was
      carried out. Measurements of scolex hooks of 81 plerocercoids and 492 adults from
      different hosts and regions were compared using basic statistics and forward
      stepwise linear discriminant analysis. The shape of the scolex and that of
      tridental hooks were found to be suitable only for differentiation of the taxa
      with a similar shape of hooks, i.e. Triaenophorus nodulosus (Pallas, 1781) from
      T. amurensis Kuperman, 1968, and T. crassus Forel, 1868 from T. meridionalis
      Kuperman, 1968 and T. orientalis Kuperman, 1968, respectively. In contrast,
      discriminant analysis did not enable reliable separation of specimens of
      individual taxa of these two morphological groups due to high intraspecific
      variability and overlaps between species. This was reflected in low
      classification efficiencies (average 83%) of all species of the T. crassus group,
      whereas all T. amurensis specimens were misidentified as T. nodulosus. The new
      data also considerably enlarge (up to twofold) the size range of the species
      described by Kuperman in 1968, which invalidates suitability of the most
      important discriminant characteristic, the width of the basal plate, for
      delimitation of Triaenophorus species. Based on the present data, all Kuperman's
      taxa are considered to represent only distinct geographical populations of T.
      nodulosus and T. crassus. As a result, T. anmurensis is synonymized with T.
      nodulosus, whereas T. orientalis is considered to be a synonym of T. crassus.
      Previous synonymisation of T. ineridionalis with T. crassus, first proposed by
      Dubinina (1987), is also accepted.

PMID- 17441436
TI  - Vitellogenesis and vitelline system in the pseudophyllidean tapeworm
      Paraechinophallus japonicus: ultrastructural and cytochemical studies.
AB  - The vitellogenesis of Paraechinophallus japonicus (Yamaguti, 1934), the first
      pseudophyllidean tapeworm of the family Echinophallidae studied using
      transmission electron microscope, is described on the basis of ultrastructural
      observations of specimens from the benthopelagic fish Psenopsis anomala (Temminck
      et Schlegel, 1844) (Perciformes: Centrolophidae). The process of vitellogenesis
      in P. japonicus follows the same general pattern observed in other tapeworms.
      Five stages of vitellocyte development have been distinguished. The first stage
      corresponds to immature cells containing ribosomes and mitochondria. The second
      stage of development is characterized by the appearance of granular endoplasmic
      reticulum and Golgi complexes, formation of shell globules and lipid droplets at
      the periphery of the cell cytoplasm. Vitellocyte of the third stage presents
      accumulation of shell globules and lipid droplets. During the fourth stage, shell
      globule clusters are formed, and lipid droplets and rosettes of alpha-glycogen
      are accumulated. Mature vitelline cells are characterized by a great number of
      lipid droplets with glycogen in the centre of the cytoplasm, whereas shell
      globule clusters are situated more peripherally. The interstitial tissue of
      vitelline follicles of P. japonicus is syncytial with long cytoplasmic
      projections extending between vitelline cells. The presence of a large amount of
      lipid droplets in the vitelline cytoplasm within the eggs of P. japonicus may be
      related to egg accumulation in the uterine sac.

PMID- 17441437
TI  - The genus Hyalomma Koch, 1844. III. Redescription of the adults and larva of H.
      (Euhyalomma) impressum Koch, 1844 (Acari: Ixodidae) with a first description of
      its nymph and notes on its biology.
AB  - In respect of its morphology, biology and epidemiology, Hyaloomma (Euhyalonuna)
      impressum Koch, 1844 is one of the more poorly studied ticks of the genus
      Hyalomma Koch, 1844. No comprehensive morphological study has been done to date,
      and the nymph has not been described. Here the adults and larva are redescribed,
      and the nymph is described for the first time. Data on hosts, geographical
      distribution and disease relationships are provided.

PMID- 17441438
TI  - Chigger mites (Acari: Trombiculidae) from wild birds in Costa Rica, with a
      description of three new species.
AB  - Three new species of chigger mites, Eutrombicula costaricensis sp. n.,
      Eutrombicula passerinoruni sp. n., and Eutrombicula hectochaeta sp. n. are
      described from wild birds from Costa Rica. Two species, Eutrombicula pacae (Floch
      et Fauran, 1957) and Parasecia findata (Brennan, 1969), are recorded for the
      first time in Costa Rica and on new host species. Data on the distribution of
      Blankaartia sinnamaryi (Floch et Fauran, 1956) in Costa Rica are also reported.

PMID- 17441439
TI  - Redescription of Monorcholepis dujardini (Krabbe, 1869) and M. passerellae
      (Webster, 1952) (Cestoda: Cyclophyllidea: Aploparaksidae) in passerine birds from
      the Holarctic Region.
AB  - Two species of avian tapeworms, Monorcholepis dujardini (Krabbe, 1869) and M.
      passerellae (Webster, 1952), of the cyclophyllidean family Aploparaksidae Mayhew,
      1925 (earlier included in the Hymenolepididae) are redescribed. Relative to
      congeners, the morphology of the strobila of both species shows strong
      similarities including a unique form of the cirrus. Separation of these species,
      however, can be based on the number (40-53 and 25-31, respectively) and size (18
      25 microm and 14-18 microm) of the rostellar hooks, although their shape in
      specimens of both species varies considerably. We examined specimens of
      Monorcholepis dujardini in Turdus iliacus L., T. philomnelos Brehm and T. nerula
      L. from the Curonian Spit (Baltic Sea, Russia), T. naumnanni Temminck from
      Chukotka, Motacilla alba L. from the Kuril Islands (Russia) and Passerella iliaca
      iliaca (Merrem) from Alaska (U.S.A.). Specimens in T. iliacus from the collection
      of O. Fuhrmann (Natural History Museum, Geneva, Switzerland) were re-studied. The
      type material (holotype and paratypes) designated as M. dujardini neoarctica
      (Webster, 1955) in Ixoreus naevius naevius (Gmelin) from Douglas Island, U.S.A.
      was re-examined and validity of this subspecies was rejected. A redescription of
      M. passerellae (Webster, 1952) was based on material in P. iliaca iliaca from
      Wisconsin (type specimen), and Point Barrow, Alaska, and on the one specimen
      recorded for the first time, in Turdus iliacus from the Palaearctic (Curonian
      Spit). Species of the genus Monorcholepis Oshmarin, 1963 and subgenus
      Aploparaksis (Tanureria) Spassky et Yurpalova, 1968 are characterized by similar
      topography of the gonads. These generic taxa and the interrelationships of
      constituent species are discussed.

PMID- 17441440
TI  - Depression and work impairment.
AB  - OBJECTIVES: This article estimates the prevalence of depression among employed
      Canadians aged 25 to 64, and examines its association with work impairment, as
      measured by reduced work activity, mental health/general disability days, and
      work absence. DATA SOURCES: Data are from the 2002 Canadian Community Health
      Survey: Mental Health and Well-being and the longitudinal household component of
      the National Population Health Survey (1994/1995 to 2002/2003). ANALYTICAL
      TECHNIQUES: Cross-tabulations were used to estimate and determine factors
      associated with the prevalence of depression among the employed population.
      Multiple logistic regression was used to examine associations between depression
      and work impairment while controlling for other variables. Longitudinal data for
      1994/1995 to 2002/2003 were used to examine the temporal sequence of depression
      and work impairment. MAIN RESULTS: In 2002, almost 4% of employed people aged 25
      to 64 had had an episode of depression in the previous year. Crosssectional
      analysis indicates that these workers had high odds of reducing work activity
      because of a long-term health condition, having at least one mental health
      disability day in the past two weeks, and being absent from work in the past
      week. Longitudinally, depression was associated with reduced work activity and
      disability days two years later.

PMID- 17441441
TI  - Going to the doctor.
AB  - OBJECTIVES: This article, based on the Andersen model, describes patterns of
      consultation with general practitioners (GPs) and specialists among Canadians
      aged 18 or older. Associations with health status and other factors are examined.
      DATA SOURCE: Estimates are based on data from the 2005 Canadian Community Health
      Survey (CCHS), cycle 3.1. ANALYTICAL TECHNIQUES: Cross-tabulations were used to
      estimate the proportion of adult Canadians who had had a GP consultation, four or
      more GP consultations, or a specialist consultation in the previous year.
      Adjusted logistic regression models were used to examine factors associated with
      such consultations when the effects of health need were taken into account. MAIN
      RESULTS: In 2005, 77% of Canadians aged 18 to 64 and 88% of seniors reported that
      they had consulted a GP in the previous year; 25% and 44%, respectively, had done
      so four or more times; and 27% and 34% had consulted a specialist. Individual
      health need, as measured by the presence of chronic conditions and self-reported
      general and mental health, was a strong determinant of service use. However, when
      need was taken into account, physician consultations were independently
      associated with age, sex, household income, race, language, urban/rural residence
      and having a regular family doctor. Seniors aged 75 or older and rural residents
      had low odds of specialist consultations, but high odds of four or more GP
      consultations. Visible minorities and Aboriginal people had lower odds of
      reporting specialist consultations than did Whites.

PMID- 17441442
TI  - Second or subsequent births to teenagers.

PMID- 17441443
TI  - Medically unexplained physical symptoms.

PMID- 17441444
TI  - [Effects of nitrous oxide and isoflurane on the L-type calcium current of rabbit
      ventricular myocytes and their modulation by beta-adrenoceptor stimulation].
AB  - BACKGROUND: We compared the effects of nitrous oxide (N2O) plus isoflurane with
      equianesthetic isoflurane alone on the L-type calcium current (I(Ca,L)), and also
      investigated their modulation of beta-adrenoceptor stimulation. METHODS: I(Ca,L)
      was recorded from enzymatically isolated rabbit ventricular myocytes using the
      whole-cell patch clamp technique. Ventricular myocytes were exposed to prepluses
      of -40 mV from a holding potential of -80 mV and then to +50 mV in 10 mV
      increments and thereafter the depolarization pulses that acquire peak currents
      were applied every 10 seconds. The changes in I(Ca,L) were measured in exposure
      to experimental gases of 1 MAC:1) 0.5% isoflurane and N2O:O2 (2:1) (I-N20) and 2)
      1.15% isoflurane and N2:O2,(2:1) (I-N2). RESULTS: I-N2O and I-N2 depressed the
      peak I(Ca,L) by 15.6 +/- 9.2 and 14.6 +/- 8.1%, respectively. In the presence of
      1 microM isoproterenol or 10 microM forskolin, the depression by I-N20 was
      significantly suppressed, but not by I-N2. CONCLUSIONS: The results show that I
      N2O and I-N2 depressed I(Ca,L) to a similar degree without beta-adrenoceptor
      stimulation. The depression by I-N2O, however, was modulated by beta-adrenoceptor
      stimulation. Beta-adrenoceptor stimulation was thus found to modulate the effect
      of N2O combined with isoflurane rather than equianesthetic isoflurane alone.

PMID- 17441445
TI  - [Intracranial subdural hematoma following dural puncture].
AB  - BACKGROUND: Intracranial subdural hematoma (SDH) following dural puncture (DP) is
      a life-threatening complication. However, the characteristics and prognosis are
      little-known. METHODS: Reports documenting intracranial SDH following DP were
      surveyed by using PubMed and the Igaku-chuou-zassi (Japana Centra Reveuo
      Medicina) database (1979-2005) and the cases were analyzed to clarify their
      characteristics and prognoses. RESULTS: Sixty-nine case reports were enrolled.
      Seventy per cent of patients underwent anesthetic procedures including spinal and
      epidural anesthesia. Fifty-two per cent of patients, many of whom receiving
      obstetrical procedures, were under 40 years of age and majority of the rest of
      over 40 years were male. Eighty per cent of patients had an onset of SDH within 1
      month after DP. Patients often showed disappearance of postural headache,
      associated with various neurological symptoms such as consciousness disorder,
      vomiting, hemiplegia and diplopia. The eighty-three per cent of patients
      recovered completely from SDH except 11 patients who died or afflicted with
      sequelae because of delayed diagnosis. CONCLUSIONS: Seventy per cent of SDH
      occured following anesthesia related procedures. Most of them had an onset within
      one month after DP The prognosis was relatively good as long as SDH could be
      diagnosed at its early stage. It was necessary to observe the disappearance of
      postural headache and associated symptoms carefully to avoid delayed diagnosis.

PMID- 17441446
TI  - [Wound healing in reconstructive head and neck surgery].
AB  - BACKGROUND: Smoking cessation and shorter operative duration are known as factors
      to improve wound healing in reconstructive head and neck surgery. We investigated
      the other factors associated with wound healing. METHODS: Informations on age,
      sex, body mass index, smoking status, serum albumin level, diabetes mellitus,
      chronic obstructive pulmonary diseases, preoperative steroid therapy,
      preoperative chemotherapy, preoperative radiation therapy, preoperative
      starvation care, American Society of Anesthesiologists physical status (ASA-PS),
      intraoperative administration of prostaglandin E1, operative duration, and type
      of flap were obtained from the medical records of 370 patients. Requirements of
      postoperative intervention were also recorded. Factors associated with wound
      healing were estimated by multivariate analysis. RESULTS: Compared with smokers,
      22 to 42 day smoking quitters, over 43 day smoking quitters, and non-smokers had
      lower incidence of wound complications; odds ratio; 95% confidence intervals (CI)
      were 0.20; 0.06-0.68, 0.19; 0.07-0.51, and 0.15; 0.05-0.45, respectively. Other
      factors and odds ratios (95% CI) associated with wound complications were
      preoperative chemotherapy; 3.02 (1.09-8.41), preoperative starvation; 0.23 (0.06
      0.84), every one minute of operation duration; 1.01 (1.00-1.01). CONCLUSIONS:
      Preoperative smoking cessation, preoperative chemotherapy, preoperative
      starvation care, and operation duration were significantly associated with wound
      healings.

PMID- 17441447
TI  - [Effect of dexmedetomidine on hemodynamics in pediatric patients following
      cardiac surgery].
AB  - BACKGROUND: Dexmedetomidine (DEX), a highly selective alpha2-adrenergic receptor
      agonist, has sedative and analgesic properties with minimal respiratory
      depression. We retrospectively evaluated the hemodynamic effects of
      dexmedetomidine in pediatric patients following cardiac surgery. METHODS: The
      subjects were twenty children aged 4 months to 15 years who had undergone cardiac
      surgery. After hemodynamics were stabilized in ICU, DEX was infused at a rate of
      0.3-0.5 microg x kg(-1) min(-1), following initial loading (0.5 microg x kg(-1)
      over 10 min). Heart rate and blood pressure were analyzed just before starting
      infusion, following 1, 3, 6 hours during infusion, and at the end of the
      infusion. RESULTS: There was no change in blood pressure during measurement. HR
      was slightly decreased during DEX infusion but not significantly. After
      discontinuation of DEX, HR was significantly increased from 109 +/- 17 to 124 +/-
      19 beats x min(-1) (mean +/- SD) (P < 0.05). Two patients were excluded from the
      study, because clinically significant bradycardia developed during DEX infusion.
      CONCLUSIONS: DEX had little effect on blood pressure in patients after cardiac
      surgery. DEX, however, had a tendency to decrease HR. Therefore, it shoud be used
      with caution in patients with low heart rate.

PMID- 17441448
TI  - [Unexpected tracheobronchomalacia during cardiac operation in a patient with
      Marfan's syndrome].
AB  - A 56-year-old man with Marfan's syndrome was scheduled for a valve-sparing aortic
      root replacement operation because of annuloaortic ectasia and aortic
      regurgitation. He had severe dyspnea. When the operation started, SpO2 decreased
      at the time of the median sternotomy, and increased by manual inflation. After
      sternal closure, PIP increased from 20 cmH2O to 28 cmH2O, SpO2 decreased from 98%
      to 66%, and the expiratory pattern indicated airway obstruction. Because
      hypoxemia persisted, we reopened the sternum, resulting in increased SpO2 and
      decreased PIP, but hypercapnea remained. Fiberoptic bronchoscopy revealed a
      narrowing of the tracheal and bronchial lumen. We suspected
      tracheobronchomalacia, and the tracheal tube was advanced to just above the
      carina. We succeeded in extubating 7 days after the operation. Since he had
      severe persisting dyspnea, we suggested reopening the partial sternum to
      decompress the intrathoracic pressure, and closing the skin. The sternum was
      reopened, and he had no dyspnea after the second operation. The mechanism of
      tracheobronchomalacia is considered to be related to the connective tissue defect
      of Marfan's syndrome. Suddenly SpO2 is decreased and PIP and Et(CO2) are
      increased after closure of the sternum. Bronchoscopy was useful in making the
      diagnosis.

PMID- 17441449
TI  - [Transient sick sinus syndrome by oral intake of high dose dehydrocodeine for
      postherpetic neuralgia].
AB  - An 88-year-old man was admitted to the intensive care unit after the ingestion of
      150 mg of dehydrocodeine. The ECG showed severe brodycardia and he was diagnosed
      as sick sinus syndrome. The recovering of sinus node function took 5 days after
      the ingestion. The complication observed suggests that transient hypoxia induced
      by ingestion of high dose DHC had affected sinus node.

PMID- 17441450
TI  - [Anesthetic management of a patient with post-emetic rupture of the esophagus
      induced by a foreign body].
AB  - Post-emetic spontaneous rupture of the esophagus (Boerhaave's syndrome) is still
      a life-threatening condition, despite recent advances in thoracic surgery and
      critical care medicine. Because a case report on anesthetic management of this
      condition is rare, we report here successful management of a 46-yr-old man with
      spontaneous esophageal rupture following forceful vomiting. He suddenly developed
      severe back pain and acute respiratory distress after vomiting during dinner and
      was brought to our emergency department. Examination on admission revealed an
      increased respiratory rate of 20 min(-1) with SpO2 97% with a facemask (O2, 3 l x
      min(-1)), a pulse rate of 100 min(-1), and a blood pressure of 138/88 mmHg. Upper
      gastrointestinal endoscopy showed a foreign body and CT examination revealed
      subcutaneous emphysema. He was diagnosed as spontaneous rupture of the esophagus.
      Emergency T-tube drainage was therefore scheduled. After semi-awake intubation
      with midazolam, general anesthesia was maintained with O2 (50%), N2O, sevoflurane
      (2%), and vecuronium infusion. A bronchial blocker was used for one lung
      ventilation to facilitate thoraco-abdominal approach. A careful attention should
      be paid to tracheal intubation to avoid any increase in intra-abdominal pressure
      to prevent further spillage of gastric contents into the mediastinum through the
      perforation. A transmural tear in the anterior wall of the esophagus was found
      and the foreign body (boiled meat) was removed. The patient recovered
      uneventfully and could be extubated on the first day in the ICU. It should be
      noted that successful management of this disease depends on accurate diagnosis
      and appropriate choice of treatments.

PMID- 17441451
TI  - [Case of coronary spasm during thoracic surgery under combined epidural-general
      anesthesia].
AB  - A 70-year-old woman, who had neither complication nor risk factors of ischemic
      heart disease, was scheduled for a partial resection of the left lung. After an
      epidural catheter was placed at the T7-8 interspace, general anesthesia was
      induced and maintained with propofol and fentanyl. Once stable vital signs had
      been confirmed, 3 ml of 0.5% ropivacaine was given through the epidural catheter.
      Bradycardia with hypotension progressively developed and continued despite the
      intravenous administration of phenylephrine, ephedrine, and atropine. Fourteen
      minutes after the injection of ropivacaine, the electrocardiogram showed an
      elevation of the ST segment. One minute later, the heart rhythm changed to a 2:1
      type second degree block. Although a bolus of 1 mg epinephrine was injected
      intravenously, severe hypotension and bradycardia persisted, leading to the
      complete block and paroxysmal ventricular tachycardia. Continuous infusion of
      nitroglycerin as well as cardiopulmonary resuscitation was started. The sinus
      rhythm with normal ST segment was eventually restored with subsequent hemodynamic
      stability. Intraoperative transesophageal echocardiography indicated a
      satisfactory cardiac wall motion. Coronary spasm was suspected because of the
      transient ST segment elevation and the absence of wall motion abnormality after
      the recovery. The clinical course of the A-V block appearing shortly after ST
      segment elevation suggested that the right coronary artery, perfusing the A-V
      node areas, was involved.

PMID- 17441452
TI  - [Two cases of left ventricular outflow tract obstruction with systolic anterior
      motion of the mitral valve due to valvular cardiomyopathy during operation].
AB  - We report two cases of left ventricular outflow tract (LVOT) obstruction with
      systolic anterior motion (SAM) of anterior mitral valve due to specific
      (secondary) cardiomyopathy during operation. The LVOT obstructions occurred and
      led to hypotension just after the induction of anesthesia in one case, and
      following the administration of nicardipine in another case. In both cases,
      preoperative diagnosis of the specific cardiomyopathy was not made. We revealed
      the LVOT obstruction with SAM using a transesophageal echocardiography (TEE) when
      the unstable hemodynamics developed. After the operations the valvular
      cardiomyopathy without LOVT obstruction was diagnosed by a cardiologist. Careful
      management is required including the TEE monitoring when we anesthetize a patient
      who is complicated not only with idiopathic cardiomyopathy but also with specific
      cardiomyopathy such as valvular or hypertensive cardiomyopathy because both types
      of cardiomyopathy develop LVOT obstruction with SAM in some pathophysiological
      conditions during operation.

PMID- 17441453
TI  - [Case of epicardial left ventricular pacing lead implantation under general
      anesthesia in a patient with severe cardiac dysfunction].
AB  - An 82-year-old man with severe cardiac dysfunction due to ischemic cardiac
      myopathy was diagnosed as indication for biventricular pacing. His left
      ventricular ejection fraction was 22%. Because of difficulty in coronary sinus
      lead fixation, epicardial lead implantation through a thoracotomy under general
      anesthesia was scheduled. Intraaortic balloon pumping (IABP) was started prior to
      the operation. Anesthesia was induced by midazolam and fentanyl, and maintained
      with fentanyl and low dose propofol infusion. Milrinone was infused throughout
      the operation. Except for just after the anesthesia induction, systolic blood
      pressure was kept well around 100 mmHg. The operation was completed without any
      ploblems. NYHA classification improved markedly (class IV to class II) by
      biventricular pacing. Using IABP, we could maintain blood pressure and stabilize
      hemodynamics during left ventricular lead implantation in a patient with severe
      heart failure.

PMID- 17441454
TI  - [Case of spontaneous intracranial hypotension associated with depressed
      consciousness].
AB  - We experienced a case of spontaneous intracranial hypotension (SIH) complicated
      with depressed consciousness after its treatment. A 56-year-old woman developed
      postural headache, and her MRI revealed bilateral chronic subdural hematoma
      (CSH). After treatment with epidural autolongous blood patch, her headache
      resolved completely. However, two days after, the patient developed depressed
      conciousness, and MRI showed brain sagging and downward brain displacement. After
      management with conservative treatment, including second epidural blood patch and
      hematoma drainage, the patient became alert and other symptoms resolved
      gradually. We demonstrated that caution should be taken for the management of
      SIH, especially in the case associated with CSH.

PMID- 17441455
TI  - [Anesthesia for a patient with xeroderma pigmentosum].
AB  - A 23-year-old man with xeroderma pigmentosum underwent laparoscopic
      cholecystectomy. He experienced transient worsening of the neurological symptom
      after anesthesia with volatile agents in the previous surgery. Because volatile
      anesthetics potentially cause genotoxic effects in patients with xeroderma
      pigmentosum, this time we chose total ir.travenous anesthesia (TIVA). The
      intraoperative management and the post-operative course were uneventful this
      time. From these two anesthesia experiences in one patient, we suggest that TIVA
      is more appropriate than anesthesia with volatile agents as a method for general
      anesthesia for xeroderma pigmentosum patients. Minimum usage of muscle relaxants
      under the monitoring of neuromuscular blockade is also recommended, since
      xeroderma pigmentosum patients are sensitive to muscle relaxants due to the
      neuronal dysfunction and muscle

PMID- 17441456
TI  - [Perioperative treatment of a patient with ectopic ACTH-producing
      pheochromocytoma].
AB  - This report deals with perioperative treatment for a very rare disease called
      ectopic ACTH-producing pheochromocytoma in a 55-year-old woman. She showed high
      norepinephrine, cortisol, and ACTH levels, and diagnosed as ectopic ACTH
      producing pheochromocytoma, by MIBG scintigraphy. An alpha-blocker and fluid
      loading for pheochromocytoma, and an adrenal cortex hormone synthesis inhibitor
      for Cushing's syndrome, were given simultaneously as a preoperative treatment.
      Propofol with nitrous oxide-oxygen-sevoflurane and epidural anesthesia were used
      for excision of the tumor, and the procedure was performed without any marked
      changes in hemodynamics. Although ectopic ACTH-producing pheochromocytoma is a
      very rare disease, it can be managed safely by appropriate preoperative treatment
      for pheochromocytoma and Cushing's syndrome.

PMID- 17441457
TI  - [Anesthetic management for high-intensity focused ultrasound (HIFU) therapy in
      prostate cancer patients].
AB  - HIFU therapy is one of epoch-making, low-invasive treatments for prostate cancer.
      We investigated 71 patients who had undergone HIFU therapy from June 2004 through
      September 2005. We mainly gave a single spinal injection followed by epidural
      catheterization with a combined spinal-epidural anesthesia kit. Three patients
      received general anesthesia because of various problems such as allergy for local
      anesthetics, ankylosing spondylitis and severe spinal deformity causing
      difficulty in lumbar puncture. Spinal anesthesia was successfully achieved in
      most patients. Twelve patients with insufficient anesthetic levels required
      additional local anesthetics via epidural catheters. We found no serious
      perioperative complications.

PMID- 17441458
TI  - [Sitting on a chair method for teaching the movement of trunk and arms for chest
      compression].
AB  - Manikin practice does not teach us how to do chest compression properly. Chest
      compression and Heimlich maneuver for a lying down subject are methods in which
      one man uses two hands and body weight. Main difference between them is how to
      hold arms on the compressed subject's body surface. Chest's elasticity is
      contributory for chest compression. At first, we can compress it easily by moving
      our trunk forward because it is not so hard but this can not be done easily
      because the chest has strong bounding force to our hands. So probably at the
      bottom, we must apply another force to remain the chest stopping there for a
      moment besides the force that moves the trunk of the body forward. Latissimus
      dorsi muscle is most likely to produce that force and it is only used
      sufficiently when legs are sustained tight. Sitting on a chair, we can move our
      trunk forward and backward without difficulty and easily pull our arms to our
      trunk. We advocate that doing the chest compression movement sitting on a chair
      is a more instructive method for beginners and the public than the manikin
      practice.

PMID- 17441459
TI  - [Leakage in anesthesia circuits--a comparison between 1998 and 2005
      investigations].
AB  - BACKGROUND: We checked for the occurrence of any leakage in an anesthesia circuit
      to estimate the present situation of airtightness of an anesthesia circuit in 55
      anesthesia machines at various medical institutions in Okinawa. METHODS: Leakage
      was detected and measured by a leak checker. RESULTS: A certain degree of leakage
      was found in 28 of the anesthesia machines (51%). The average and maximal amounts
      of leakage in the anesthesia machines were 0.26, and 1.29 l x min(-1),
      respectively. Thirty-eight of anesthesia machines met the standards of a low flow
      leak test (69%). The average and maximal amounts of leakage in the inside circuit
      were 0.02, and 0.20 l x min(-1), respectively. The leak points of the inside
      circuit were present in a unidirectional valve for an oxygen sensor (14%) and for
      unknown reason (7%). The average and maximal amounts of leakage in the outside
      circuit were 0.24, and 1.29 l x min(-1), respectively. Leak points in the inside
      circuit were found in the corrugated breathing tube (82%) and canister (32%).
      CONCLUSIONS: Most instances of leakage of the above described anesthesia circuits
      were identified in the corrugated breathing tube and canister. As a result of our
      findings, we strongly recommend that these parts be checked very carefully during
      pre-anesthetic leak tests.

PMID- 17441460
TI  - [Usefulness of an earphone-type infrared tympanic thermometer for intraoperative
      core temperature monitoring].
AB  - BACKGROUND: Thermometers widely used intraoperatively are invasive and non
      hygienic. We developed an earphone-type infrared tympanic thermometer and
      evaluated its usefulness as a core temperature monitor. METHODS: Sixteen adult
      patients who required nonabdominal surgery under general anesthesia were enrolled
      in this study. After induction of general anesthesia, thermistor probes were
      inserted into the rectum and esophagus for measurements of rectal and esophageal
      temperatures, respectively. An earphone-type infrared tympanic thermometer was
      inserted into the ear canal on one side. These measured temperatures were
      monitored and recorded at 1-min intervals. Regression analysis and Bland-Altman
      analysis were used to compare the data (tympanic/rectal temperatures) with
      esophageal temperature as a core temperature. RESULTS: Tympanic temperature
      showed a good correlation with esophageal temperature (r = 0.976, n= 2490, P <
      0.001). The mean difference between these temperature monitors was+0.06 degrees
      C, and 2x standard deviation (SD) was 0.32 degrees C. Rectal temperature also
      showed a good correlation with esophageal temperature (r = 0.946, P < 0.001). The
      mean difference between these monitors was+0.22 degrees C, and 2 SD was 0.28.
      CONCLUSIONS: The earphone-type tympanic thermometer can be used in a clinical
      setting as a reliable core temperature monitor.

PMID- 17441461
TI  - [Pentax-AWS improves laryngeal view compared with Macintosh blade during
      laryngoscopy and facilitates easier intubation].
AB  - BACKGROUND: The PENTAX-AWS (AWS), combined with PBLADE is a novel tracheal
      intubation device which allows indirect visualization of the vocal cords without
      the alignment of the oral, pharyngeal axes required for direct laryngoscopy.
      Intubation procedure can be monitored on a built-in CCD monitor. METHODS: We
      compared the laryngeal view obtained with the Macintosh laryngoscope with that
      obtained with the AWS in 100 patients scheduled for elective anesthesia.
      Laryngeal view was determined by Cormack & Lehane classification modified by
      Cook, first using the Macintosh laryngoscope with the patient's head and neck in
      the sniffing position, followed by the AWS with the head and neck in a neutral
      position. The time taken to pass the endotracheal tube, the incidence of tube
      impingement on the arytenoids and the total number of intubation attempts were
      also recorded. RESULTS: The best laryngeal view obtained with the Macintosh
      laryngoscope in 100 cases were Grade I: 65, IIa: 16, IIb: 8, IIIa: 6, IIIb: 5,
      IV: 0. With AWS, the laryngeal views obtained were all grade I. The total time to
      pass the tube with the AWS was 19.5 +/- 7.9 s and the number of intubation
      attempts was 1.05 +/- 0.2. The Cormack grade obtained with the Macintosh
      laryngoscope did not affect the AWS view. The tube touched the right arytenoid in
      5 cases but successful intubation was achieved by adjusting the blade direction.
      CONCLUSIONS: We conclude that the PENTAX-AWS provides a better laryngeal view
      than the Macintosh laryngoscope and facilitates easier intubation under vision in
      a higher proportion of patients.

PMID- 17441462
TI  - [Survey of nerve injury associated with epidural/spinal anesthesia in Japan which
      occurred in the year 2004].
AB  - BACKGROUND: The incidence of nerve injury associated with epidural/spinal
      anesthesia has not been sufficiently investigated in Japan. PURPOSE: The
      incidence of nerve injury caused by inappropriate epidural/spinal puncture or
      catheter placement was examined using data obtained by a survey conducted by the
      Japanese Society of Anesthesiologists for the year 2004. METHODS: In a survey for
      the year 2004, 1,218,371 anesthetic procedures were registered, among which
      548,819 patients were estimated to be anesthetized under epidural/spinal
      procedures with or without general anesthesia. Twenty nine patients were reported
      to have incurred nerve injury due to inappropriate epidural/spinal puncture or
      catheter placement. RESULTS: Seven cases of spinal cord and 22 cases of
      peripheral nerve injury were reported, with estimated incidences of 1/78,000 and
      1/25,000 procedures, respectively. Spinal cord injury developed before the start
      of surgery in 4 cases, intraoperatively in 1 case, and after the end of surgery
      in 2 cases. Permanent nerve damage developed in 4 patients with spinal cord
      injury and 7 patients with peripheral nerve injury. Eighty three percent of these
      events were reported to be preventable. CONCLUSIONS: The incidence of nerve
      injury caused by regional anesthesia in Japan seems to be comparable to those
      reported in the developed countries. To reduce the incidence of this
      complication, cautious evaluation of the risk/benefit balance in performing
      regional anesthesia, improving education and supervision of the procedures, and
      establishing better communication between anesthesiologists and surgeons
      concerning the timing of catheter removal and the postoperative coagulation state
      seem to be important.

PMID- 17441463
TI  - [Evaluation of skin-moisturizing effects of oral or percutaneous use of plant
      ceramides].
AB  - This study was undertaken to evaluate the assay performance of two methods for
      measuring the water-holding capacity of the skin: Skicon-200 and Tewameter which
      determine the water content in the stratum corneum and transepidermal water loss,
      respectively. Based on these findings, we studied the effects of newly developed
      skin moisturizers made of plant ceramides. The within-run as well as day-to-day
      reproducibility of the methods were both satisfactory. When rice-derived NIPPN
      ceramide RC was used topically for 3 weeks by 23 healthy volunteers, the water
      content in the stratum corneum of the leg was significantly increased to 141% of
      the baseline value in comparison with that after placebo use (111%) (p < 0.05),
      and the transepidermal water-loss was significantly suppressed to 23% of the
      baseline in comparison with that after placebo use (39%) (p < 0.01). When 20 mg
      or 40 mg/day of corn-derived NIPPN ceramide CP was given orally for 3 weeks, the
      water content in the stratum corneum of the leg was significantly increased to
      290% and 394% of the baseline value, respectively, in comparison with that after
      placebo administration (141%) (p <0.05), and the transepidermal water loss was
      suppressed to 33 and 14% (p < 0.05) of the baseline values, respectively, in
      comparison with that after placebo administration (69%). These data by Skicon-200
      and Tewameter suggest that the two plant ceramides are promising as skin
      moisturizing agents not only for topical use but also for oral use.

PMID- 17441464
TI  - Determination of single nucleotide polymorphisms in N-acetyltransferase2 gene
      using an electrochemical DNA chip and an automated DNA detection system.
AB  - An electrochemical DNA chip using an electrochemically active intercalator and
      DNA probe immobilized on a gold electrode has been developed for genetic
      analysis. In this study, N-acetyltransferase2 (NAT2) gene polymorphisms (C481T
      G590A G857A) were determined by the electrochemical DNA chip and the automated
      DNA detection system that performs hybridization reaction, washing, detection,
      and data analysis. Human genomic DNAs were extracted from blood and DNA fragments
      containing the three polymorphisms were amplified by the polymerase chain
      reaction (PCR) method. Double-stranded PCR products were treated with T7
      exonuclease and single-stranded target DNAs were obtained. A sample containing
      the single-stranded target DNAs was injected into a cassette including the
      electrochemical DNA chip and set in an automated system. The turnaround time for
      genotyping with this system was 90 min. A total of 38 samples were automatically
      genotyped by an SNP determination algorithm. The results of genotype were
      completely consistent with those determined by the polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) analysis. Consequently, this
      method requires no labeling step and has the advantage of realizing a compact and
      automatic system, and so the system is expected to contribute to personalized
      medicine based on genotype.

PMID- 17441465
TI  - [Clinical evaluation after an introduction of our manual for antibiotic use
      during perioperative period and a notification policy of use of the antibiotics
      for MRSA].
AB  - Abuse of antibiotics results in unfavorable consequences in healthcare associated
      infection control, such as emergence of multiple-resistant bacteria, and
      increased medical cost and nosocomial infection. In 2003, we had an outbreak of
      Methicillin-resistant Staphylococcus aureus (MRSA) in a surgical ward of Akita
      University Hospital. With the aim of preventing inappropriate use of antibiotics
      during perioperative period, a guideline for usage of antibiotics, which is made
      by surgeons themselves, was introduced, and a notification policy of the
      antibiotic use for MRSA was also applied in 2004. In this study, we evaluated the
      influence of the antibiotic restriction on changes in antibiotics consumption,
      prevalence of multiple-drug-resistant pathogens, and their susceptibility to
      antibiotics. The notification policy reduced the cost and amount of antibiotics
      and the prevalence of multiple-drug-resistant pathogens, such as MRSA and
      Pseudomonas aeruginosa. The susceptibility of bacteria, such as Staphylococcus
      aureus, MRSA, Serratia marcescens and Pseudomonas aeruginosa, to antibiotics
      showed a remarkable improvement. The introduction of notification policy for
      usage of antibiotics has a favorable influence on the infection control in
      hospitals and re education of doctors.

PMID- 17441466
TI  - [Flow cytometric analysis using live/dead staining for yeast cells which were
      autoclaved and treated with various disinfectants].
AB  - Flow cytometric analysis using live/dead staining dyes was applied to
      discriminate yeast cells treated with autoclave and various disinfectants. One
      fluorogenic dye, propidium iodide cannot leak into live cells with intact
      membranes, whereas another fluorogenic dye, thiazole orange is permeant and can
      enter all cells, live and dead. Thus a combination of these two dyes can classify
      cell populations into live, injured and dead cells. When the yeast cells were
      autoclaved at 121 degrees C for 5 min, almost all the cells were classified as
      being dead, but some yeast strains contained a little injured cells (up to 8.5%).
      It was also demonstrated that none of the yeast cells autoclaved could produce a
      visible colony on the agar plate. The 70% ethylalcohol was the most effective
      disinfectant tested. Almost all the yeast cells treated were classified as being
      dead, and no visible colony appeared after agar plate incubation. The cell
      suspensions of yeast treated with 0.5% chlorhexidine contained injured cells with
      >95%, but no visible colony appeared. Whereas, the numbers of live yeast cells
      after treatment with 0.025% benzalkonium chloride were less than detectable
      counts (<1.0%) by flow cytometry, however, visible colonies appeared on the agar
      plate with 10(1) to 3.6 x 10(3) colony forming units/ml. With these results, it
      became apparent that the combination with fluorogenic dyes and flow cytometry can
      provide a reliable test method to discriminate dead and/or injured cells from the
      reproductive live yeast cells, and is applicable for further studies. However, it
      should be noted that minimum detectable levels are sometimes far different
      between the standard colony forming assay and the flow cytometric determination.

PMID- 17441467
TI  - [Phlebotomy-related complications. Introduction].
AB  - Recently, management of the central phlebotomy station by the clinical laboratory
      has become the norm and phlebotomy is a routine job for many medical
      technologists. Although venipuncture-related accidents, such as nerve injury,
      unfortunately happen in a low but fixed ratio, there is little information to
      avoid this risk. This topic consists of three excellent reviews: Dr. Tanabe
      reviewed "Iatrogenic peripheral nerve injury; mechanism and therapy", Dr. Ohnishi
      reviewed "effective methods to prevent nerve injury at venipuncture", and Dr.
      Kitamura reviewed "An effective and efficient method of painless venipuncture in
      children". I believe these three articles will be of great help to many medical
      technologists and clinical laboratory physicians to perform phlebotomy safely.

PMID- 17441468
TI  - [Iatrogenic peripheral nerve injury; mechanism and therapy].
AB  - The pain remaining after a needle stick is categorized as neuropathic pain. CRPS
      (Complex Regional Pain Syndrome) is a typical disease in this category.
      Neuropathic pain is extremely intractable when it becomes chronic pain, inducing
      psychological and physical pain in patients over a long period of time.
      Neuropathic pain is a complex system caused by various factors, and its mechanism
      remains unclear. For prevention, medical practioners should carefully select
      centesis, and apply necessary measures corresponding to the situation. There is
      no established treatment for neuropathic pain. We usually treat the disease with
      nerve block and drug therapy. Nerve block is useful for pain relief. We typically
      use a sympathetic nerve block (SGB; stellate ganglion block, IRSB; intravenous
      regional sympathetic block et. al.) as the initial treatment. In the stage of
      chronic pain, it is very important to improve patients' ADL (activity of daily
      living) and QOL (quality of life). If neuropathic pain is suspected, it is
      crucial to treat at an early stage. Therefore, it should be emphasized that when
      pain persists after a needle stick, the patient should immediately consult a pain
      clinician or an orthopedist.

PMID- 17441469
TI  - [How to prevent phlebotomy-related nerve injury].
AB  - Phlebotomy-related nerve injury is relatively rare but could be a serious
      complication of venipuncture; however, widely recognized and effective methods to
      prevent nerve injury at venipuncture have not been established. By considering
      the anatomical features of peripheral nerves and veins of the arm, several
      techniques may be feasible. To prevent median nerve injury, which is the most
      serious among the nerve injuries in the arm, the following order of vein
      selection is recommended: (1) radial vein (2) median cubital vein (3) basilic
      vein (4) forearm veins (5) veins of the back of the hands. However, this order
      should be changed according to the status of the actual veins of the patient. To
      avoid the needle from being inserted too deeply, short needles such as butterfly
      needles may be preferred. Although probing is a very dangerous procedure which
      must be avoided, re-direction of the needle is an acceptable procedure if it is
      performed once per venipuncture. In addition to these technical efforts, it is
      critical to ask each patient before venipuncture whether he or she has
      experienced nerve injury during previous phlebotomy in order to avoid unnecessary
      repetitive nerve injuries in the same patient. In order to avoid such situations,
      we have established a computer-based system to alert phlebotomists to the
      complications which patients have experienced during venipuncture. These and
      other methods should be tested in many institutes and data should be
      systematically collected to investigate whether phlebotomy-related nerve injury
      can be effectively prevented.

PMID- 17441470
TI  - [Effective and efficient method of painless venepuncture in children].
AB  - Venepuncture for routine blood sampling is not only a very distressing experience
      for a considerable number of children but also leading to unreliable data because
      of hemolytic sample by patients' fighting during procedure. The children express
      both high levels of distress during venepuncture and anticipation of the
      procedure. Therefore, prevention or reduction of distress should focus on both
      phases of the procedure. To this end, several elements should be considered:
      preparation of procedural information, distraction during painful procedures, and
      local anesthesia. Current concepts to understand these elements are presented in
      this review.

PMID- 17441471
TI  - [Development of molecular pathology analysis testing which can be practiced in
      the hospital laboratory. The clinical application of a transcription factor
      activation test].
AB  - The nuclear factor-kappa B (NF-kappaB) family of transcription factors is known
      to play an important role in the regulation of the immune system. NF-kappaB is
      activated by bacterial and viral antigens, which lead to the production of
      proinflammatory cytokines and chemokines. The rapid detection of activated NF
      kappaB by systemic inflammatory response syndrome (SIRS) is considered to be
      crucial for the treatment of patients with septicemia. The aim of the present
      study was to evaluate the sensitivity of two methods, electrophoretic mobility
      shift assay (EMSA) and transcription factor enzyme-linked immunoassay (TF-ELISA).
      TF-ELISA detected 25ng of recombinant human NF-kappaB p50 (rhp50) and 5 microg of
      TNFalpha-stimulated HeLa nuclear protein, while EMSA detected approximately 100
      ng of rhp50 and 10 microg of HeLa nuclear protein. We found that TF-ELISA was
      more sensitive than EMSA in detecting NF-kappaB; however, it was judged that the
      3-6 hour measuring time required in TF-ELISA was excessively long for patients
      with SIRS. Therefore, the development of new analytical methods with improved
      sensitivity and measurement time was necessary for the detection and
      quantification of activated NF-kappaB protein in the hospital laboratory.
      Consequently, we have developed a new NF-kappaB analyzer based on surface plasmon
      resonance (SPR), which is recognized as one of the most sensitive direct optical
      detection methods. This method can detect nanomolar concentrations of NF-kappaB
      within 15 minutes. In addition, we have developed new experimental apparatus for
      the detection of NF-kappaB based on fluorescence correlation spectroscopy (FCS),
      which is able to analyze binding between DNA and protein in the liquid phase. At
      present, we are carrying out clinical trials using this new transcription factor
      analysis apparatus for SIRS patients.

PMID- 17441472
TI  - [Blood cytokine levels as a clinical laboratory test].
AB  - Cytokines have not been employed in clinical laboratory tests because of the many
      biological activities of individual cytokines and too complicated cytokine
      network. However, abnormal laboratory data and symptoms can be interpreted by
      blood cytokine levels. [Cytokines attributable to abnormal data and symptoms] For
      example, cytokines attributable to abnormal data and symptoms in rheumatoid
      arthritis are as follows: joint pain: TNFalpha, IL-1, IL-6, and IL-18; general
      fatigue and appetite loss: TNFalpha and IL-1; leukocytosis: G-CSF produced by IL
      1-stimulated macrophages etc; thrombocytosis: megakaryocyte potentiating activity
      of IL-6; anemia: hepcidin up-regulated by IL-6, which inhibits iron absorption
      from the intestine, and IL-1, which decreases the blood iron level and promotes
      ferritin synthesis. [Differential diagnosis using blood cytokine levels] Blood
      cytokine levels are useful and important in the differential diagnosis of
      inflammatory disorders such as neutrophilia, eosinophilia, and especially in
      distinguishing tumoral fever from infectious fever in malignant lymphomas.
      [Disease/disorder-specific cytokines] In recent years, disease- or disorder
      specific cytokines have been identified, making cytokines more important in
      clinical use. For example, IL-18 for adult-onset Still disease; IFNgamma for
      hemophagocytic syndrome; IL-5 for allergic disorders; thrombopoietin for immune
      thrombocytopenic purpura; vascular endothelial growth factor for POEMS syndrome;
      PTH-rP for malignancy associated hypercalcemia. [Flow cytometric measurement of
      cytokines] Recently, a flow cytometric method has been developed in addition to
      ELISA. With this method, 30 cytokine concentrations can be measured
      simultaneously within four hours with a wide range of detection limit and high
      cost performance. Cytokines will be included in laboratory tests with this
      method.

PMID- 17441473
TI  - [Role of endothelial dysfunction in the development of severe sepsis--the
      pathomechanism, evaluation by laboratory tests and new therapeutic strategies].
AB  - Tumor necrosis factor (TNF) is critically involved in biological responses
      against various insults. TNF excessively produced by monocytes or macrophages
      activates endothelial cells and neutrophils, thereby inducing endothelial cell
      injury. Endothelial cells are capable of inhibiting TNF production by producing
      prostaglandins that inhibit TNF production. Sensory neurons play an important
      role in promotion of the endothelial production of prostaglandins by releasing
      calcitonin gene-related peptide. Neutrophils activated by TNF release a huge
      amount of neutrophil elastase that is capable of decreasing endothelial
      prostaglandin production. Consequently, TNF production is enhanced, leading to
      the development of multi-organ failure in sepsis. E-selectin, an endothelial
      leukocyte adhesion molecule, is released from the endothelial cell membrane by
      the action of TNF and exists as soluble E-selectin in plasma. The detection of
      increases in plasma levels of soluble E-selectin in patients with systemic
      inflammatory response syndrome predicts the imminent onset of acute respiratory
      syndrome. Early detection of increases in plasma levels of soluble E selectin by
      a rapid assay system, developed by the authors, enables early effective treatment
      of patients with sepsis.

PMID- 17441474
TI  - [Myeloproliferative diseases caused by Jak2 gene mutation].

PMID- 17441475
TI  - [NKT cell-mediated immunotherapy for hematological malignancies].

PMID- 17441476
TI  - [Efficacy of percutaneous vertebroplasty for multiple myeloma].
AB  - Multiple myeloma is commonly associated with bony lesions and skeletal
      destruction. Percutaneous vertebroplasty (PVP) was performed in five patients
      with multiple myeloma for vertebral body fractures. Four patients reported a
      decrease in their pain after the procedure, and in all patients an improvement in
      their performance status could be noted. Complications included fever in two
      patients. PVP can be safely and effectively performed in patients with vertebral
      body fractures caused by multiple myeloma.

PMID- 17441477
TI  - [Complications in the central nervous system during chemotherapy for childhood
      acute lymphoblastic leukemia: JACLS ALL-02 study].
AB  - We evaluated central nervous system (CNS) complications treated under the ALL-02
      protocol of the Japan Association of Childhood Leukemia Study (JACLS) from April
      2002 to March 2005. According to NCI Toxicity Criteria, 17 events of grade 3 and
      4 CNS complications were reported in 15 out of 541 patients. Out of these CNS
      complications, leukoencephalopathy was seen in 5 patients; seizure in 5;
      cerebrovascular disease in 3; conscious disturbance in 2; and hypertensive
      encephalopathy and reversible posterior leukoencephalopathy syndrome in one
      patient each. The complications were intensively observed during induction
      therapy and the last of the early phase chemotherapy. The protocol treatment was
      stopped or modified in most patients after CNS complications. MRI imaging
      demonstrated no improvement in one patient with leukoencephalopathy who developed
      an isolated CNS relapse, while other patients were alive and remain in their
      first complete remission without any neurological sequelae. Further studies will
      be required to analyze risk factors for CNS complications during chemotherapy not
      accompanied by irradiation and to establish alternative treatments after the
      appearance of such CNS complications.

PMID- 17441478
TI  - [Copper deficiency with pancytopenia, bradycardia and neurologic symptoms].
AB  - A 48-year-old man was referred to our hospital in December, 2005 because of
      general fatigue, gait disturbance and bradycardia. He had a history of
      polysurgery due to recurrent ileus and had been treated with home total
      parenteral nutrition for the short-bowel syndrome since 2003. Clinical findings
      on admission included marked emaciation and severe weakness of the extremities.
      Pancytopenia was noted in the peripheral blood. The serum levels of copper and
      ceruloplasmin were 3 microg/dl and 3 mg/dl, respectively, while Vit. B12 and
      folate were within the normal range. The bone marrow demonstrated cytoplasmic
      vacuolation in the myeloid and megakaryocytic series, and sideroblastic changes.
      No evidence of hematologic malignancies was presented. The diagnosis was copper
      deficiency and the patient was treated with copper supplementation. Four weeks
      after copper therapy, the serum level of copper rose to 50 microg/dl and
      ceruloplasmin to 14 mg/dl. Significant improvements in the hematologic profile,
      ECG findings and weakness of extremities were noted. Although bicytopenia (anemia
      and neutropenia) is considered to be a feature of hematologic disorders caused by
      copper deficiency, the present case showed pancytopenia. The exact mechanism of
      the unusual association of thrombocytopenia and other abnormalities with copper
      deficiency remains to be elucidated.

PMID- 17441479
TI  - [T-cell rich B-cell lymphoma associated with neutrophilia and thrombocytosis].
AB  - A 49-year-old man was admitted with high-grade fever, night sweating and cervical
      lymphadenopathy in September 2005. On examination, both neutrophilia and
      thrombocytosis were noted in the peripheral blood, a bone marrow examination
      revealed marked both myeloid and megakaryocytic hyperplasia. The sera obtained at
      initial presentation showed an elevated levels of granulocyte-colony stimulating
      factor (G-CSF) and interleukin-6 (IL-6). A pathologic diagnosis of T-cell rich B
      cell lymphoma was made based on an inguinal lymph node biopsy. Following
      treatment with CHOP accompanied by rituximab (R-CHOP), both the neutrophilia and
      thrombocytosis subsided after 3 courses of R-CHOP, resulting in a complete
      remission after 4 courses of chemotherapy. Neutrophilia, thrombocytosis and T
      cell rich B-cell lymphoma in this patient were considerably ameliorated with
      chemotherapy. We report here a patient with T-cell rich B-cell lymphoma
      associated with both neutrophilia and thrombocytosis, suggesting that the
      lymphoma triggered both myeloid and megakaryocytic hyperplasia.

PMID- 17441480
TI  - [Acute appendicitis during bone marrow suppression following chemotherapy for
      acute leukemia; report of three cases].
AB  - We report here on the clinical courses of three cases of acute appendicitis
      during a period of myelosuppression after chemotherapy for acute leukemia. The
      patients were two boys and one girl with a mean age 11 years (range, 10-12). Two
      of the patients had acute myeloid leukemia (AML) in subtypes M1 and M2, while the
      third had acute lymphoblostic leukemia of subtype L1 (FAB classification). All
      patients had clinical features of fever, abdominal pain, and elevations of C
      reactive protein. However, the typical peritoneal signs were blunted and
      developed transiently in two cases. All patients were diagnosed as having
      appendicitis with abdominal computed tomography scan (CT), and proceeded to
      appendectomy. With perioperative support utilizing antibiotics, antifungal
      agents, blood components, and granulocyte-colony stimulating factor, surgical
      intervention was successfully performed, and all patients were able to undergo
      chemotherapy courses shortly after surgery. Histological examinations of the
      appendectomy specimens showed infiltration of most of the lymphoid cells and a
      few neutrophils in the wall of the appendix. Enhanced CT was useful in diagnosing
      appendicitis, which needs to be considered in cases presenting with clinical
      symptoms such as described here. Because of a high mortality rate after appendix
      perforation, immediate surgical intervention with sufficient perioperative
      support should be performed.

PMID- 17441481
TI  - [Multicentric Castleman disease-like case characterized by lymphadenopathy and
      polyclonal hypergammaglobulinemia associated with so-called Mikulicz disease].
AB  - A 73-year-old male was admitted in January 1999 with hyperimmunoglobulinemia with
      a serum IgG level of 6530 mg/dl, bilateral eyelid tumors, bilateral submandibular
      swelling, and swelling of the superficial lymph nodes. A left submandibular gland
      biopsy showed severe chronic sialoadenitis with fibrosis. A left cervical lymph
      node biopsy showed invasion by many mature lymphocytes and plasma cells, but no
      lymphoma cells. The patient was diagnosed as having so-called Mikulicz disease
      associated with a disease similar to multicentric Castleman disease (MCD)
      characterized by multicentric lymphadenopathy and polyclonal
      hyperimmunoglobulinemia. Steroid therapy (prednisolone, 20 mg/day) was effective
      in reducing the symptoms, the bilateral eyelid tumors and the swelling of the
      bilateral submandibular glands and superficial lymph nodes. The lack of any
      increase of serum IL-6 suggested that this case had a hitherto unknown etiology,
      other than MCD.

PMID- 17441482
TI  - [Combination therapy with low-dose cyclosporin A, azathiopurine, and prednisolone
      for a child with refractory chronic idiopathic thrombocytopenic purpura].
AB  - We report on a boy with refractory chronic idiopathic thrombocytopenic purpura
      (ITP) successfully treated with combination therapy composed of low-dose
      cyclosporin A (CsA), azathiopurine, and prednisolone. The patient was diagnosed
      as having ITP at 5 years of age, and received high-dose intravenous
      immunoglobulin (IVIG), followed by oral prednisolone, intravenous pulsed
      dexamethasone, oral cepharantin, and intermittent IVIG therapies. Because there
      were no or only transient responses to these medical therapies over 2 years, he
      was splenectomized. However, 3 months after the splenectomy, his platelet counts
      fell to below 10 x 10(3)/microl accompanied by wet purpura. We resumed low-dose
      intermittent IVIG treatment for 1 year without sustained efficacy. We then
      started combination therapy with CsA (2.5 mg/kg/day), azathiopurine (1.7
      mg/kg/day), and prednisolone (0.8 mg/kg/day). Complete remission was achieved
      within 2 weeks and the platelet counts remained > 50 x 10(3)/microl even after
      tapering off the prednisolone and azathiopurine at 6 and 12 months, respectively
      and have moreover remained normal for more than 10 months after completion of 2
      years of CsA treatment. There were no adverse events during the therapeutic
      course. This is the first pediatric case of ITP treated with CsA in Japan. Such
      combination therapy may be promising and tolerable for childhood ITP with
      splenectomy failure.

PMID- 17441483
TI  - Calculating CVD risk.

PMID- 17441484
TI  - Diabetes and insanity. 1907.

PMID- 17441485
TI  - Adopt an evidence-based approach to menorrhagia.

PMID- 17441486
TI  - Tailor treatment to the patient in endometriosis.

PMID- 17441487
TI  - Detecting polycystic ovary syndrome.

PMID- 17441488
TI  - Young women should be encouraged to attend for cervical screening.

PMID- 17441489
TI  - Blood testing diagnostic for parathyroid disease.

PMID- 17441490
TI  - Achieving optimum pain control in terminally ill patients at home.

PMID- 17441491
TI  - Topics are best studied in revision groups.

PMID- 17441492
TI  - Eczema.

PMID- 17441494
TI  - Workplace violence online survey.

PMID- 17441495
TI  - Elder abuse and neglect.

PMID- 17441497
TI  - Call for action on asylum seekers' health.

PMID- 17441498
TI  - A background and critical analysis of the treatment of pneumocystis carinii
      pneumonia (PCP) in HIV/AIDS.

PMID- 17441499
TI  - Spotlight on indigenous health.

PMID- 17441500
TI  - Improving maternity care for Aboriginal women.

PMID- 17441501
TI  - Protecting nurses wherever they may be.

PMID- 17441502
TI  - All in the family: atypical Hsp70 chaperones are conserved modulators of Hsp70
      activity.
AB  - Divergent relatives of the Hsp70 protein chaperone such as the Hsp110 and Grp170
      families have been recognized for some time, yet their biochemical roles remained
      elusive. Recent work has revealed that these "atypical" Hsp70s exist in stable
      complexes with classic Hsp70s where they exert a powerful nucleotide-exchange
      activity that synergizes with Hsp40/DnaJ-type cochaperones to dramatically
      accelerate Hsp70 nucleotide cycling. This represents a novel evolutionary
      transition from an independent protein-folding chaperone to what appears to be a
      dedicated cochaperone. Contributions of the atypical Hsp70s to established
      cellular roles for Hsp70 now must be deciphered.

PMID- 17441503
TI  - Pathogenic chaperone-like RNA induces congophilic aggregates and facilitates
      neurodegeneration in Drosophila.
AB  - Protein aggregation is a hallmark of many neurodegenerative diseases. RNA
      chaperones have been suggested to play a role in protein misfolding and
      aggregation. Noncoding, highly structured RNA recently has been demonstrated to
      facilitate transformation of recombinant and cellular prion protein into
      proteinase K-resistant, congophilic, insoluble aggregates and to generate
      cytotoxic oligomers in vitro. Transgenic Drosophila melanogaster strains were
      developed to express highly structured RNA under control of a heat shock
      promoter. Expression of a specific construct strongly perturbed fly behavior,
      caused significant decline in learning and memory retention of adult males, and
      was coincident with the formation of intracellular congophilic aggregates in the
      brain and other tissues of adult and larval stages. Additionally, neuronal cell
      pathology of adult flies was similar to that observed in human Parkinson's and
      Alzheimer's disease. This novel model demonstrates that expression of a specific
      highly structured RNA alone is sufficient to trigger neurodegeneration, possibly
      through chaperone-like facilitation of protein misfolding and aggregation.

PMID- 17441505
TI  - A pilot study with a therapeutic vaccine based on hydroxyapatite ceramic
      particles and self-antigens in cancer patients.
AB  - We describe an approach to produce an autologous therapeutic antitumor vaccine
      using hydroxyapatite (HA) for vaccinating cancer patients. The novel approach
      involved (1) the purification of part of the self-tumor antigens/ adjuvants using
      column chromatography with HA, (2) the employ of HA as a medium to attract
      antigen-presenting cells (APCs) to the vaccination site, and (3) the use of HA as
      a vector to present in vivo the tumor antigens and adjuvants to the patient's
      APCs. The vaccine was prepared using and combining HA particles, with at least 3
      heat shock proteins (gp96 was one of them possibly with chaperoned
      proteins/peptides as shown in the slot blots) and with proteins from the cell
      membrane system (including Hsp70, Hsp27, and membrane proteins). The timing of HA
      degradation was tested in rats; the HA particles administered under the skin
      attracted macrophages and were degraded into smaller particles, and they were
      totally phagocytized within 1 week. In patients (n = 20), the vaccine was then
      administered weekly and showed very low toxicity, causing minor and tolerable
      local inflammation (erythema, papule, or local pain); only 1 patient who received
      a larger dose presented hot flashes, and there were no systemic manifestations of
      toxicity or autoimmune diseases attributed to the vaccine. Our study suggests
      that this therapeutic vaccine has shown some efficacy producing a positive
      response in certain patients. Stable disease was noted in 25% of the patients
      (renal carcinoma, breast carcinoma, and astrocytoma), and a partial response was
      noted in 15% of the patients (breast carcinoma and astrocytoma). The most
      encouraging results were seen in patients with recurrent disease; 4 patients in
      these conditions (20%) are disease free following the vaccine administration.
      However, we do not want to overstate the clinical efficacy in this small number
      of patients. The therapeutic vaccine tested in our study is working by activating
      the T-cell response as was shown in the comparative histological and
      immunohistochemical study performed in the pre- and postvaccine biopsy taken from
      a patient with inflammatory breast carcinoma. However, we cannot ruled out that
      the vaccine could also be producing an antibody(ies)-mediated response. In
      conclusion, this therapeutic vaccine based on HA ceramic particles and self
      antigens can be safely administered and is showing some encouraging clinical
      results in cancer patients.

PMID- 17441504
TI  - GroEL/S substrate specificity based on substrate unfolding propensity.
AB  - Phage P22 wild-type (WT) coat protein does not require GroEL/S to fold but
      temperature-sensitive-folding (tsf) coat proteins need the chaperone complex for
      correct folding. WT coat protein and all variants absolutely require P22
      scaffolding protein, an assembly chaperone, to assemble into precursor structures
      termed procapsids. Previously, we showed that a global suppressor (su)
      substitution, T1661, which rescues several tsf coat protein variants, functioned
      by inducing GroEL/S. This led to an increased formation of tsf:T1661 coat
      protein:GroEL complexes compared with the tsf parents. The increased
      concentration of complexes resulted in more assembly-competent coat proteins
      because of a shift in the chaperone-driven kinetic partitioning between
      aggregation-prone intermediates toward correct folding and assembly. We have now
      investigated the folding and assembly of coat protein variants that carry a
      different global su substitution, F170L. By monitoring levels of phage production
      in the presence of a dysfunctional GroEL we found that tsf:F170L proteins
      demonstrate a less stringent requirement for GroEL. Tsf:F170L proteins also did
      not cause induction of the chaperones. Circular dichroism and tryptophan
      fluorescence indicate that the native state of the tsf: F170L coat proteins is
      restored to WT-like values. In addition, native acrylamide gel electrophoresis
      shows a stabilized native state for tsf:F170L coat proteins. The F170L su
      substitution also increases procapsid production compared with their tsf parents.
      We propose that the F170L su substitution has a decreased requirement for the
      chaperones GroEL and GroES as a result of restoring the tsf coat proteins to a WT
      like state. Our data also suggest that GroEL/S can be induced by increasing the
      population of unfolding intermediates.

PMID- 17441506
TI  - Cadmium induces an apoptotic response in sea urchin embryos.
AB  - Cadmium is a heavy metal toxic for living organisms even at low concentrations.
      It does not have any biological role, and since it is a permanent metal ion, it
      is accumulated by many organisms. In the present paper we have studied the
      apoptotic effects of continuous exposure to subacute/sublethal cadmium
      concentrations on a model system: Paracentrotus lividus embryos. We demonstrated,
      by atomic absorption spectrometry, that the intracellular amount of metal
      increased during exposure time. We found, using terminal deoxynucleotidyl
      transferase-mediated dUTP nick-end labeling assay, that long treatments with
      cadmium triggered a severe DNA fragmentation. We demonstrated, by
      immunocytochemistry on whole-mount embryos, that treatment with cadmium causes
      activation of caspase-3 and cleavage of death substrates alpha-fodrin and lamin
      A. Incubating the embryos since fertilization with Z-DEVD FMK, a caspase-3
      inhibitor, we found, by immunocytochemistry, that cleavage by caspase-3 and
      cleavage of death substrates were inactivated.

PMID- 17441507
TI  - Neuronal expression of constitutive heat shock proteins: implications for
      neurodegenerative diseases.
AB  - Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and
      amyotrophic lateral sclerosis have been termed "protein misfolding disorders."
      These diseases differ widely in frequency and impact different classes of
      neurons. Heat shock proteins provide a line of defense against misfolded,
      aggregation-prone proteins and are among the most potent suppressors of
      neurodegeneration in animal models. Analysis of constitutively expressed heat
      shock proteins revealed variable levels of Hsc70 and Hsp27 in different classes
      of neurons in the adult rat brain. The differing levels of these constitutively
      expressed heat shock proteins in neuronal cell populations correlated with the
      relative frequencies of the previously mentioned neurodegenerative diseases.

PMID- 17441508
TI  - SGT2 and MDY2 interact with molecular chaperone YDJ1 in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, Sgt2 was thought to be the homologue of vertebrate
      SGT (small glutamine tetratricopeptide repeat-containing protein). SGT has been
      known to interact with both Hsp70 and Hsp90. However, it was not clear whether
      Sgt2 might have a similar capacity. Here, we showed that Ssa1/Ssa2 (yeast heat
      shock cognate [Hsc]70), Hsc82 (yeast Hsp90), and Hsp104 coprecipitated with Sgt2
      from yeast lysates. Another molecular chaperone, Ydj1, known to interact with
      Ssal and Hsc82, also coprecipitated with Sgt2. Synthetic lethality between SGT2
      and YDJ1 was observed after the cells were under stress, although Sgt2 might not
      interact physically with Ydj1. We also found that Mdy2 interacted with the N
      terminal region of Sgt2 and that Mdy2 appeared to interact physically with Ydj1.
      Mdy2 therefore may mediate the association of Ydj1 and Sgt2. In addition, the
      mating efficiency of mdy2delta, sgt2delta, and mdy2deltasgt2delta strains was
      reduced to a similar extent. Compared with mdy2delta and ydj1delta cells,
      ydj1deltamdy2delta cells, however, showed a further suppression in mating
      efficiency. Moreover, MDY2 interacted genetically with YDJ1. These results
      suggest that protein complexes containing Sgt2 and Mdy2 bring molecular
      chaperones together to carry out certain chaperoning functions.

PMID- 17441509
TI  - Administration of the stress protein gp96 prolongs rat cardiac allograft
      survival, modifies rejection-associated inflammatory events, and induces a state
      of peripheral T-cell hyporesponsiveness.
AB  - High-dose gp96 has been shown to inhibit experimental autoimmune disease by a
      mechanism that appears to involve immunoregulatory CD4+ T cells. This study
      tested the hypothesis that high-dose gp96 administration modifies allograft
      rejection and associated inflammatory events. Wistar cardiac allografts were
      transplanted into Lewis recipient rats and graft function was monitored daily by
      palpation. Intradermal administration of gp96 purified from Wistar rat livers
      (100 microg) at the time of transplantation and 3 days later significantly
      prolonged allograft survival (14 vs 8 days in phosphate-buffered saline [PBS]
      treated recipients; P = 0.009). Rejected allografts from gp96-treated animals
      were significantly less enlarged than allografts from their PBS-treated
      counterparts (2.8 vs 4.3 g; P < 0.004). Gp96 was also effective when administered
      on days 1 and 8 (13 vs 7 days), but not if it was derived from recipient (Lewis)
      liver tissue or administered on days 0, 3, and 6. In parallel studies, CD3+ T
      cells from gp96-treated untransplanted animals secreted less interleukin (IL)-4,
      IL-10, and interferon (IFN)-gamma after in vitro polyclonal stimulation than CD3+
      T cells from PBS-treated animals. Gp96 administration might therefore influence
      the induction of immunity to coencountered antigenic challenges and inflammatory
      events by inducing what appears to be a state of peripheral T-cell
      hyporesponsiveness.

PMID- 17441511
TI  - The mouth/body connection.

PMID- 17441510
TI  - Hsp70 may protect cardiomyocytes from stress-induced injury by inhibiting Fas
      mediated apoptosis.
AB  - Expression of Hsp70 is an endogenous mechanism by which living cells adapt to
      stress and the protection of Hsp70 may interfere with the apoptotic machinery in
      a variety of ways. Here, we observed the change of Hsp70 expression in rat
      myocardium under stress and explored the protective effect of Hsp70 on the Fas
      mediated pathway to cardiomyocyte apoptosis. The results showed that restraint
      stress led to cardiac dysfunction and structural damage of the myocardium, as
      well as activation of the Fas pathway. A similar increase in the Fas expression
      level, caspase-8/3 activity, and the apoptotic rate of the cardiomyocyte also
      were found, which indicated that Fas-mediated apoptosis of cardiomyocytes might
      be one of the mechanisms of cardiomyocyte injury induced by stress. Changes in
      Hsp70 levels and distribution occurred during the stress process, which
      correlated with the severity of myocardium injury. Heat preconditioning induced
      the upregulation of Hsp70 synthesis, which in turn may have mitigated subsequent
      restraint stress-induced damage, including electrocardiography (ECG) abnormality,
      myocardium damage, and cell death. Moreover, Hsp70 overexpression induced by heat
      preconditioning had no effect on Fas expression in the cardiomyocyte, but could
      inhibit activation of caspase-8/3 induced by the Fas signaling pathway and, as a
      result, prevent cell apoptosis. These results suggest that Hsp70 is capable of
      protecting the cardiomyocyte from stress-induced injury by inhibiting Fas
      mediated apoptosis, and Hsp70 could be considered a target in future drugs to
      prevent cardiovascular injury caused by stress.

PMID- 17441512
TI  - Periodontal potential in your hygiene department: a new profit center.

PMID- 17441513
TI  - An aid to transferring aesthetic mock-ups to the patient: the H-T Open Window
      stent.

PMID- 17441514
TI  - Exclusive interview: Dr. Irwin Smigel. Interview by Dean Mersky.

PMID- 17441515
TI  - What's new in Ni-Ti rotary instrumentation: part 1.

PMID- 17441516
TI  - Access: the good, the bad, and the ugly.

PMID- 17441517
TI  - Preparation and restoration of a fractured tooth utilizing a new temporary
      system.

PMID- 17441518
TI  - Posterior direct composites: clinical protocol.

PMID- 17441519
TI  - Combining radiosurgery and Captek restorations in complicated tissue cases: part
      2.

PMID- 17441520
TI  - A template-driven composite bonding approach to direct composite bonding.

PMID- 17441521
TI  - Understanding impression materials and techniques.

PMID- 17441522
TI  - Surgical removal of impacted third molars.

PMID- 17441523
TI  - Overview of new ADA CDT 2007-2008 codes.

PMID- 17441524
TI  - Digital dentistry and beyond is now!

PMID- 17441525
TI  - Buyers' guide to rotary files. Dentists must target safe, efficient files.

PMID- 17441526
TI  - Buyers' guide. Digital radiography-intraoral. Digital radiography provides
      greater accuracy to the dentist.

PMID- 17441527
TI  - Dentistry today and yesterday: then and now. Consultant offers input on the
      future of computers. Tax and dental relief.

PMID- 17441528
TI  - Older male sexual partner as a marker for sexual risk-taking in adolescent
      females in Nova Scotia.
AB  - PURPOSE: To examine age differences between Nova Scotia women aged 15-19 and
      their male sexual partners, and to determine if those adolescents with older
      partners were more likely to have engaged in sexual risk-taking behaviours.
      METHODS: A cross-sectional survey (response rate=91%) administered in May 2003
      assessed the following sexual risk behaviours: (a) not using condom/hormonal
      contraception at last vaginal intercourse; (b) having unplanned vaginal
      intercourse while using alcohol or drugs; (c) having more than one partner in the
      previous year; (d) vaginal intercourse before age 15; and (e) ever having anal
      intercourse. Univariate analysis was carried out to determine associations of
      sexual risk behaviours with partner age difference. Logistic regression was then
      used to examine behaviours associated with partner age (p < 0.15) in univariate
      analysis. RESULTS: Of the young women surveyed, 520 (47.7%) had had vaginal
      intercourse in the previous year; 515 of these provided information on their last
      partner's age. Over 10% had partners four or more years older. In multivariate
      analysis, having a partner > or =4 years older was associated with not using a
      condom at last intercourse (OR 2.15; 95% Cl 1.10-4.20), having more than one
      partner in the previous year (OR 21.9; 95% Cl 1.13-4.28) and having unplanned
      vaginal intercourse while using alcohol or drugs (OR 2.66; 95% Cl 1.34-5.28).
      CONCLUSIONS: A significant number of female adolescents have older male sexual
      partners, and such relationships are markers for high-risk sexual behaviours.
      Partner age is an important consideration for health professionals providing
      sexual health advice to young women.

PMID- 17441529
TI  - Patterns and correlates of pubertal development in Canadian youth: effects of
      family context.
AB  - BACKGROUND: Current health literature suggests that there has been a decline in
      the age of pubertal onset, and that pubertal development is influenced by social
      context. Unfortunately, contemporary Canadian-specific data have not been
      available. This study examined the odds of having entered puberty at various ages
      during adolescence, before and after controlling for the effects of family socio
      economic status and family structure. METHODS: Longitudinal data for this study
      were drawn from the first four cycles of the National Longitudinal Survey of
      Children and Youth. The final sample consisted of 7977 adolescents ranging in age
      from 10 to 17. Pubertal status of the participants was identified based on pubic
      hair, facial hair growth, and voice change, for boys; and pubic hair, breast
      development, and menstruation, for girls. Trajectories of pubertal development
      were analyzed with HLM growth curve modelling techniques. RESULTS: The results
      indicated that, compared to boys, the odds of having entered puberty at age 13
      were 6.45 times higher for girls and that girls go through puberty more quickly.
      Low family socio-economic status and living with a stepfather were found to
      predict early onset of pubertal development. CONCLUSION: Contextual factors are
      related to pubertal development. Additional research is needed to develop a more
      solid understanding of how psychosocial factors interact to predict gendered
      patterns of pubertal development.

PMID- 17441530
TI  - The decline in physical activity among adolescent students: a cross-national
      comparison.
AB  - BACKGROUND: The decline in physical activity during adolescence is a key public
      health concern. This comparative study assesses whether the age-related decline
      in physical activity among high school students occurs similarly in the United
      States (U.S.) and Ontario, whether the decline in physical activity is steady
      throughout the age range, or whether any declines are age-specific. METHODS: Data
      are based on self-reports of 9th- to 12th-graders derived from the 2001 Youth
      Risk Behavior Survey (n=13,503) and the 2001 Ontario Student Drug Use Survey
      (n=1322). Physical activity is measured by the number of days of vigorous
      physical activity during the past 7 days. RESULTS: In both samples, there was a
      dominant and steady decline in physical activity between ages 14 and 18 years.
      The number of activity days was higher in the U.S. than in Ontario holding
      constant age and sex. However, a significant sample-by-age interaction showed
      that the decline in the percentage of U.S. students reporting 3 or more physical
      activity days was greater than it was in Ontario. CONCLUSIONS: While the pattern
      of decline was shown to be similar, the decline was stronger among US
      adolescents. Future research should examine additional factors influencing the
      decline in activity and the optimal timing of programs to reduce the decline.

PMID- 17441531
TI  - Evaluating the role of social marketing campaigns to prevent youth gambling
      problems: a qualitative study.
AB  - BACKGROUND: Gambling among adolescents is a growing public health concern. To
      date, social marketing as a strategy to address problem gambling among youth has
      not been widely used. METHODS: A qualitative study through the use of focus
      groups was conducted to explore adolescents' exposure to existing prevention
      campaigns and their message content and communication strategy preferences for a
      youth gambling social marketing campaign. FINDINGS: Participants prefer that
      youth gambling ads depict real-life stories, use an emotional appeal and portray
      the negative consequences associated with gambling problems. They further
      recommend illustrating the basic facts of gambling using simple messages that
      raise awareness without making a judgement. Participants caution against the
      "don't do it" approach, suggesting it does not reflect the current youth gambling
      culture. CONCLUSION: This study should serve as a starting point for the
      development of a gambling prevention social marketing campaign. Targeting
      variables and campaign strategies highlighted should be considered in the early
      stages of development and tested along the way.

PMID- 17441532
TI  - [Do organizational barriers to pneumococcal and influenza vaccine access exist?].
AB  - CONTEXT: Despite the implementation of a Quebec immunization program against
      influenza and pneumococcal disease (PQIIP), vaccine coverage has remained low.
      There have been many studies on personal barriers to vaccination, but few have
      explored other kinds of barriers. OBJECTIVES: To explore the presence of barriers
      in relation to the organization of the health care system and to propose
      recommendations for increasing vaccine coverage. METHODS: Within a mixed
      protocol, a phone survey of 996 people in the target population and a case study
      implicating the follow-up of the PQIIP with all the site and actor categories via
      43 semistructured interviews and 4 focus groups were realized. Survey data
      underwent a descriptive statistical analysis. Qualitative analysis followed the
      Miles and Huberman approach. RESULTS: The results indicate the presence of
      barriers with regard to information accessibility. These include access to: the
      physicians' recommendation, knowledge of the efficacy or the security of
      vaccines, and admissibility of clients to the PQIIP. Organizational barriers were
      also found to limit access to vaccination, especially in terms of restricted
      choices of time and location. Coordination and incentives mechanisms are not
      optimal. Removal of organizational barriers depends more on strategic rather than
      structural factors. CONCLUSION: Addressing organizational barriers should be an
      important component of strategies aimed at improving vaccine coverage. Public
      health authorities should focus on strategic management of the information and
      inter-organizational environment.

PMID- 17441533
TI  - Invasive pneumococcal infections in Canadian children, 1998-2003: implications
      for new vaccination programs.
AB  - BACKGROUND: We conducted active surveillance for invasive pneumococcal disease to
      assess the serotype and antibiotic resistance patterns in Canada prior to
      universal infant immunization programs, in most provinces. METHODS: Active
      surveillance was conducted by the 12 centres of the Canadian Paediatric Society's
      Immunization Monitoring Program, Active (IMPACT). This report includes children
      16 years of age and younger with S. pneumoniae isolated from a normally sterile
      site, in 1998-2003. RESULTS: During six years of surveillance, 1,868 eligible
      cases were reported. The 7-valent pneumococcal conjugate vaccine (PCV7) matched
      79% of isolates, including 84% from 6-23 month olds and 80% from 2-5 year olds.
      The proportion of isolates matched by PCV7 significantly decreased over the
      surveillance period from 81% in 1998 to 73% in 2003 (p = 0.005). The 23-valent
      polysaccharide vaccine (PPS) matched 90% of isolates from children 2 years or
      older. Penicillin non-susceptibility rate was stable at 16% of isolates.
      Cefotaxime/ceftriaxone resistance rate was 5% and limited to penicillin-resistant
      isolates. Serotypes found in PCV7 accounted for 89% of penicillin-resistant
      isolates (100% including cross-reacting types 6A and 19A). CONCLUSION: PCV7
      matched three quarters of the isolates from young children as immunization
      programs began; therefore some program failures are inevitable. Children > or =5
      years with predisposing conditions need the broader protection of 23-valent PPS
      vaccine and special attention from providers to ensure receipt. The rate of
      penicillin resistance remained steady over the last six years. The majority of
      isolates non-susceptible to penicillin are found in PCV7.

PMID- 17441534
TI  - Mycobacterium tuberculosis infection in First Nations preschool children in
      Alberta: implications for BCG (bacille Calmette-Guerin) vaccine withdrawal.
AB  - BACKGROUND: On April 1, 2004, BCG (bacille Calmette-Guerin), a tuberculosis (TB)
      control vaccine, was discontinued in all but four high-risk communities in
      Alberta. To confirm the safety of vaccine withdrawal, and for future planning,
      the annual risk of infection (ARI) was determined in preschool First Nations
      children. METHODS: First Nations children born into reserve communities in
      Alberta between April 1, 1998 and March 31, 2004, and still living on reserve in
      2004-2005, were identified. Health centre TB histories were validated by cross
      referencing the birth cohort with the provincial TB Registry. Children that were
      not BCG vaccinated and not known to be tuberculin skin test (TST) positive
      underwent a TST. Birth cohort children were grouped as follows: (i) BCG
      vaccinated; (ii) BCG non-vaccinated, no TST; (iii) BCG non-vaccinated, TST; (iv)
      BCG vaccination status unknown. The ARI was calculated and the age and community
      characteristics of the groups were compared. RESULTS: There were 8447 children in
      the 6-year birth cohort, 4699 (55.6%) vaccinated, 2696 (31.9%) non-vaccinated,
      and 1052 (12.5%) whose vaccination status was unknown. Of the non-vaccinated
      children, 1921 (71.3%) were tested and only 2 were TST positive. No other TST
      positive, BCG non-vaccinated children were identified in the TB Registry cross
      match. The prevalence of infection in 2004-2005 was 0.1% and the ARI was 0.03%.
      The community risk of TB exposure was comparable in tuberculin-tested and non
      tested BCG non-vaccinated children. CONCLUSION: In low BCG-uptake First Nations
      communities in Alberta, the ARI is low and it is safe to withdraw BCG.

PMID- 17441535
TI  - Physical activity, cardiorespiratory fitness and body mass index as predictors of
      substantial weight gain and obesity: the Canadian physical activity longitudinal
      study.
AB  - BACKGROUND: Obesity is a growing health issue in Canada and the identification of
      the determinants of obesity is important for the development of prevention
      strategies. The purpose of this investigation was to determine the relationships
      between physical activity, cardiorespiratory fitness, body mass index (BMI), and
      the development of future obesity. METHODS: The sample included 459 adults (18+
      y; 223 men, 236 women) from the Canadian Physical Activity Longitudinal Study
      (PALS; 2002-04). Data on physical activity, smoking, alcohol consumption, BMI,
      and cardiorespiratory fitness (VO2max) were collected in 1981 and 1988. The mean
      BMI, physical activity, and VO2max were calculated across the 1981 and 1988
      measures. Self-reported height and weight were collected in the 2002-04 survey,
      and participants were classified as overweight (BMI 25 to 29.9 kg/m2) or obese
      (BMI 230 kg/m2). Logistic regression was used to predict overweight, obesity or
      substantial weight gain (10 kg or more) in 2002-04, controlling for age, sex,
      smoking and alcohol use. RESULTS: Higher VO2max in 1981-88 was associated with
      lower odds of obesity in 2002-04 (OR = 0.87; 95% Cl: 0.76-0.99, p < 0.05), and
      higher BMI in 1981-88 was associated with higher odds of obesity in 2002-04
      (1.84; 1.52-2.20, p < 0.0001). In women, higher VO2max (0.82; 0.72-0.93) resulted
      in lower odds of a 10 kg weight gain. CONCLUSIONS: The results indicate that
      cardiorespiratory fitness and previous BMI are important predictors of future
      weight gain and obesity, and should be incorporated in strategies to identify
      individuals at increased risk of obesity.

PMID- 17441537
TI  - Prevalence and associated factors of hepatitis C infection (HCV) in a multi-site
      Canadian population of illicit opioid and other drug users (OPICAN).
AB  - BACKGROUND: Hepatitis C virus (HCV) infection is highly prevalent in illicit drug
      user populations, with three in four new HCV infections related to this risk
      behaviour and a growing HCV disease burden in Canada. Using data from a multi
      site cohort study of illicit opioid users in five Canadian cities (OPICAN), this
      paper explores the prevalence and predictors of HCV status in this high-risk
      population. METHODS: HCV status of cohort participants was assessed by salivary
      antibody test. Univariate relationships of HCV status with select variables were
      examined on the basis of cohort baseline data, and subsequently multivariate
      models using logistic regression to determine independent predictors of HCV
      status were generated. RESULTS: 54.6% of the analysis sample (n=482) was HCV
      positive. Significant differences in terms of HCV prevalence existed across the
      sites. Significant variables in the final stepwise logistic regression model
      included age, site (Toronto), unprotected sex, injecting drug use, drug treatment
      and incarceration in past year, in addition to opioid use in combination with non
      opioids. DISCUSSION: Besides drug injecting, various other socio-behavioural
      factors were associated with HCV status in our cohort. On this basis,
      interventions focusing solely on injection risks are overly limited in scope to
      prevent HCV transmission in the high-risk population of illicit drug users and
      need to be broadened. Prevention efforts should also target young injectors as a
      priority.

PMID- 17441536
TI  - Hepatitis B knowledge, testing and vaccination levels in Chinese immigrants to
      British Columbia, Canada.
AB  - BACKGROUND: Little is known about hepatitis B (HBV) and liver cancer control in
      Chinese in Canada. Liver cancer, a significant health problem in Asia, is
      preventable and can be controlled through HBV blood testing, vaccination, and
      community education about HBV. OBJECTIVE: The overall goal was to increase HBV
      testing and vaccination in Chinese adult Canadians. The objective was to present
      findings on HBV testing, vaccination and knowledge in Chinese immigrants.
      METHODS: 504 randomly selected Chinese adult immigrants residing in Vancouver
      responded to the survey which examined HBV blood testing and vaccination
      practices, HBV knowledge levels and socio-demographic characteristics. Face-to
      face interviews were conducted in Cantonese, Mandarin, or English. RESULTS: 57%
      of participants reported that they had received HBV blood testing, 38% had been
      vaccinated, and 6% were known HBV carriers. There were gender differences, with
      lower rates of testing and vaccination, and higher chronic carrier rates, among
      men. Over 80% knew that HBV can be spread by asymptomatic persons and can cause
      cirrhosis and liver cancer. However, confusion existed about the routes of HBV
      transmission. INTERPRETATION: A sizeable proportion of Chinese adult immigrants
      in Vancouver have not been tested or vaccinated for HBV. Knowledge level,
      especially about routes of HBV transmission, was low. This is a concern, given
      that chronic HBV infection is the most common cause of liver cancer in Asian
      North Americans. To improve knowledge, reduce risk of infection and the burden of
      chronic infection and its sequelae in immigrant populations, continuing
      educational efforts are needed.

PMID- 17441538
TI  - Epidemiological analysis of Chlamydia trachomatis and Neisseria gonorrhoeae in
      Saskatoon Health Region.
AB  - BACKGROUND: The incidence rates of Chlamydia trachomatis (Ct) and Neisseria
      gonorrhoeae (GC) in Saskatoon Health Region are approximately double the national
      average. A descriptive study was designed to try to determine why. METHODS: The
      objectives of the study were: (1) to determine whether or not the introduction of
      a new detection method that is less invasive and more sensitive led to more tests
      being ordered and a higher percentage of positive cases; (2) to determine what
      percentage of physicians and STI clinic nurses notified Public Health within 72
      hours of suspected Ct or GC; (3) to determine what percentage of physicians and
      STI clinic nurses listed sexual contact information; and (4) to compare
      recurrence rates between patients treated by physicians and STI clinic nurses.
      RESULTS: The number of tests ordered for Ct and GC increased substantially from
      10,425 in 1998 to 28,885 in 2003, while the percentage of positive cases
      decreased from 7.2% to 3.6%. Only 1.3% of physicians and 9.1% of STI clinic
      nurses notified Public Health within 72 hours of a suspected case. 51.2% of
      physicians listed sexual contact information in comparison to 85.4% of STI clinic
      nurses. Recurrence rates of Ct or GC within one year of initial treatment were
      26% lower for patients treated by STI clinic nurses (5.7%) than for physicians
      (7.2%). CONCLUSIONS: There is a need for additional education for health care
      providers in the management of sexually transmitted infections in Saskatoon
      Health Region.

PMID- 17441539
TI  - Socio-economic correlates of municipal-level pollution emissions on Montreal
      Island.
AB  - BACKGROUND: Differential exposure to environmental hazards is one component of
      the social gradient in health. Few studies have investigated the association
      between socioeconomic characteristics and environmental hazards in a Canadian
      context. We assessed the relationships between pollution emissions and socio
      economic characteristics for 27 municipalities on Montreal Island. METHODS:
      Pollution emissions were determined using Environment Canada's National Pollutant
      Release Inventory (NPRI) for the periods 1995-1996 and 2000-2001. Variables
      included the number of reporting industries, the average annual releases, and the
      average annual releases density. These data were cross-referenced with socio
      economic data from the 1996 and 2001 Canadian Censuses, respectively. RESULTS:
      For both periods, pollution measures were inversely related to the average
      monthly amount of owners' major payments, the average income of households, the
      proportion of workers in the tertiary sector, and the proportion of individuals
      with a university education. Pollution measures were positively associated with
      the unemployment rate, the proportion of workers in the secondary sector, and the
      proportion of individuals with less than high school education. CONCLUSION: Socio
      economic characteristics are associated with municipal-level pollution emissions
      on Montreal Island. Whether higher emissions are indicative of higher pollution
      exposure requires further investigation.

PMID- 17441540
TI  - Exploring rural health inequalities at a local scale: the case of Portneuf,
      Quebec.
AB  - BACKGROUND: The most common way of accounting for the countryside in health
      studies has been to compare it, as a whole, to the city. Furthermore, most of the
      work on small area health inequalities has been confined to major urban centres.
      To counter this trend, in this paper, we explore small area health inequalities
      in the predominantly rural county of Portneuf (population = 44,545), Quebec. Such
      information can be of interest for local health planning. METHODS: Three sources
      of data were used to define neighbourhood units: historical data, socio-economic
      data and perceptions of local stakeholders. Demographic, socioeconomic and
      general health status indicators were calculated by neighbourhood unit. For
      health status indicators, data came from mortality files (1998 to 2002),
      hospitalization files (2001/02) and the 2001 census for disability (individuals
      who reported being often limited in their daily activities) and the reference
      population. RESULTS: The county of Portneuf was subdivided into 8 neighbourhoods.
      Differences between neighbourhoods were noticeable for demographic, socio
      economic and all health status indicators. The greatest differences were found
      between the town of Pont-Rouge (population=4975) and the hinterland of the towns
      of Donnacona (population=6125) and Saint-Marc-des-Carrieres (population=3160).
      The most striking was a difference of 6 to 8 years of disability-free life
      expectancy between the two groups, to the advantage of Pont-Rouge. CONCLUSION:
      Although measuring rural health inequalities at a local level has some
      methodological limitations, true health inequalities exist in the county of
      Portneuf. These now need to be examined further.

PMID- 17441541
TI  - Gender, income and immigration differences in depression in Canadian urban
      centres.
AB  - BACKGROUND: Immigrants tend to initially settle in urban centres. It is known
      that immigrants have lower rates of depression than the Canadian-born population,
      with the lowest rates among those who have arrived recently in Canada. It is
      established that women and low-income individuals are more likely to have
      depression. Given that recent immigration is a protective factor and female
      gender and low income are risk factors, the aim of this study was to explore a
      recent immigration-low income interaction by gender. METHODS: The study used 2000
      01 Canadian Community Health Survey data. The sample consisted of 41,147 adults
      living in census metropolitan areas. Logistic regression was used to examine the
      effect of the interaction on depression. RESULTS: The prevalence of depression in
      urban centres was 9.17% overall, 6.82% for men and 11.44% for women. The
      depression rate for recent immigrants was 5.24%, 3.87% for men and 6.64% for
      women. The depression rate among low-income individuals was 14.52%, 10.79% for
      men and 17.07% for women. The lowest-rate of depression was among low-income
      recent immigrant males (2.21%), whereas the highest rate was among low-income non
      recent immigrant females (11.05%). CONCLUSIONS: This study supports previous
      findings about the effects of income, immigration and gender on depression. The
      findings are novel in that they suggest a differential income effect for male and
      female recent immigrants. These findings have implications for public health
      planning, immigration and settlement services and policy development.

PMID- 17441542
TI  - Factors affecting change over time in self-reported health.
AB  - BACKGROUND: Self-reported health status has become a conventional measure of
      health status at the population level. Further, the literature supports its use
      as a valid indicator of morbidity and mortality. However, relatively little
      attention has been paid to how self-reported health status changes over time or
      the factors affecting change. This paper explores the factors affecting health
      status change over time using data from a neighbourhood health survey. METHODS:
      Two rounds (2001; 2003) of health survey data (n=671) were collected across 4
      distinct neighbourhoods in Hamilton, Ontario. Logistic regression analysis is
      used to predict change in self-reported health status between the two time
      periods as well as determinants of change using a range of compositional,
      contextual and collective characteristics of individuals as potential explanatory
      variables. RESULTS: Results reveal that approximately one third of participants
      experienced a change in health status between the two survey years.
      Interestingly, the key factors affecting change in health status are
      compositional characteristics of individuals (e.g., smoking, health care use) as
      opposed to contextual (e.g., neighbourhood of residence) or collective (e.g.,
      marital status). Contrary to published literature, the current study does not
      reveal any significant links between a change in health status and either gender
      or age. CONCLUSION: These results inform our understanding of both the stability
      of health ratings over time and the determinants of health status change. Further
      research should be undertaken to enhance this understanding; in particular,
      studies with larger sample sizes, longer time frames and more sensitive
      indicators of composition, context and collective are needed.

PMID- 17441543
TI  - Conventionality and cognitive development: learning to think the right way.

PMID- 17441544
TI  - Conventionality and contrast in language and language acquisition.

PMID- 17441545
TI  - How an appreciation of conventionality shapes early word learning.

PMID- 17441546
TI  - Pragmatic and prescriptive aspects of children's categorization.

PMID- 17441547
TI  - Play, games, and the development of collective intentionality.

PMID- 17441548
TI  - The role of information about "convention," "design," and "goal" in representing
      artificial kinds.
AB  - In this chapter, we have considered the nature and development of our capacities
      for the representation of artificial kinds. We have presented a range of evidence
      collected using varying methods and from our own laboratories and those of others
      that speaks to the question of the kinds of information that might be central to
      knowledge of artifacts and their functions in human semantic memory. One key
      argument here has been that despite the fact that information about shared
      convention has been argued to play an important role in understanding of the
      "proper" uses of artifacts, just as it does in the case of the use of linguistic
      symbols within language communities, there are important differences between the
      two cases, and indeed across development, decisions about categories and
      functions dissociate. We have argued here that the nonarbitrary relationship
      between the material kind and mechanical structure of artifacts and the functions
      that can be supported undercuts the force of information about convention as
      important to determining proper artifact function. Shared convention appears less
      important for determining this facet of our semantic memory for artifacts than it
      does in supporting the proper relationship between linguistic symbols and the
      categories of artifact to which they refer.

PMID- 17441549
TI  - Conventionality in family conversations about everyday objects.
AB  - Children's developing understanding that words have conventional meanings and
      objects have conventional functions emerges in parent-child activity and
      conversation. Drawing on family conversations in everyday settings, the chapter
      explores an apparent paradox between a global analysis of conventionality as
      stable shared knowledge and a local notion of conventions as flexibly negotiated
      in activity.

PMID- 17441550
TI  - Systems-level insights into cellular regulation: inferring, analysing, and
      modelling intracellular networks.
AB  - Genes and gene products interact on several levels, forming transcriptional
      regulatory-, protein interaction-, metabolic- and signal transduction networks.
      Genetic, biochemical and molecular biology techniques have been used for decades
      to identify biological interactions; newly developed high-throughput methods now
      allow for the construction of genome-level interaction maps. In parallel, high
      throughput expression data paired with computational algorithms can be used to
      infer networks of interactions and causal relationships capable of producing the
      observed experimental data. Graph-theoretical measures and network models are
      more and more frequently used to discern functional and evolutionary constraints
      in the organisation of biological networks. Perhaps most importantly, the
      combination of interaction and expression information allows the formulation of
      quantitative and predictive dynamic models. Some of the dominant experimental and
      computational methods used for the reconstruction or inference of cellular
      networks are reviewed, also the biological insights that have been obtained from
      graph-theoretical analysis of these networks, and the extension of static
      networks into various dynamic models capable of providing a new layer of insight
      into the functioning of cellular systems is discussed.

PMID- 17441551
TI  - Parameter estimation in ordinary differential equations for biochemical processes
      using the method of multiple shooting.
AB  - In silico investigations by simulating dynamical models of biochemical processes
      play an important role in systems biology. If the parameters of a model are
      unknown, results from simulation studies can be misleading. Such a scenario can
      be avoided by estimating the parameters before analysing the system. Almost all
      approaches for estimating parameters in ordinary differential equations have
      either a small convergence region or suffer from an immense computational cost.
      The method of multiple shooting can be situated in between of these extremes. In
      spite of its good convergence and stability properties, the literature regarding
      the practical implementation and providing some theoretical background is rarely
      available. All necessary information for a successful implementation is supplied
      here and the basic facts of the involved numerics are discussed. To show the
      performance of the method, two illustrative examples are discussed.

PMID- 17441552
TI  - Graph theory and networks in Biology.
AB  - A survey of the use of graph theoretical techniques in Biology is presented. In
      particular, recent work on identifying and modelling the structure of bio
      molecular networks is discussed, as well as the application of centrality
      measures to interaction networks and research on the hierarchical structure of
      such networks and network motifs. Work on the link between structural network
      properties and dynamics is also described, with emphasis on synchronisation and
      disease propagation.

PMID- 17441553
TI  - Efficient algorithms for ordinary differential equation model identification of
      biological systems.
AB  - Algorithms for parameter estimation and model selection that identify both the
      structure and the parameters of an ordinary differential equation model from
      experimental data are presented. The work presented here focuses on the case of
      an unknown structure and some time course information available for every
      variable to be analysed, and this is exploited to make the algorithms as
      efficient as possible. The algorithms are designed to handle problems of
      realistic size, where reactions can be nonlinear in the parameters and where data
      can be sparse and noisy. To achieve computational efficiency, parameters are
      mostly estimated for one equation at a time, giving a fast and accurate parameter
      estimation algorithm compared with other algorithms in the literature. The model
      selection is done with an efficient heuristic search algorithm, where the
      structure is built incrementally. Two test systems are used that have previously
      been used to evaluate identification algorithms, a metabolic pathway and a
      genetic network. Both test systems were successfully identified by using a
      reasonable amount of simulated data. Besides, measurement noise of realistic
      levels can be handled. In comparison to other methods that were used for these
      test systems, the main strengths of the presented algorithms are that a fully
      specified model, and not only a structure, is identified, and that they are
      considerably faster compared with other identification algorithms.

PMID- 17441554
TI  - Analysis of lactose metabolism in E. Coli using reachability analysis of hybrid
      systems.
AB  - We propose an abstraction method for medium-scale biomolecular networks, based on
      hybrid dynamical systems with continuous multi-affine dynamics. This abstraction
      method follows naturally from the notion of approximating nonlinear rate laws
      with continuous piecewise linear functions and can be easily automated. An
      efficient reachability algorithm is possible for the resulting class of hybrid
      systems. An efficient reachability algorithm is possible for the resulting class
      of hybrid systems. An approximation for an ordinary differential equation model
      of the lac operon is constructed, and it is shown that the abstraction passes the
      same experimental tests as were used to validate the original model. The well
      studied biological system exhibits bistability and switching behaviour, arising
      from positive feedback in the expression mechanism of the lac operon. The
      switching property of the lac system is an example of the major qualitative
      features that are the building blocks of higher level, more coarse-grained
      descriptions. The present approach is useful in helping to correctly identify
      such properties and in connecting them to the underlying molecular dynamical
      details. Reachability analysis together with the knowledge of the steady-state
      structure are used to identify ranges of parameter values for which the system
      maintains the bistable switching property.

PMID- 17441555
TI  - Reducing perinatal HIV transmission among HIV-infected pregnant women.
AB  - BACKGROUND: In 1995, Help Understand and Guide-Me (HUG-Me) began planning the
      implementation of Protocol 076, a treatment that aids in the reduction of
      perinatal transmission of human immunodeficiency virus (HIV). A program
      coordinator and a social worker worked with a 1572 bed-hospital system to
      successfully implement the protocol. METHODS: Program effectiveness was tracked
      through monitoring of client outcomes. HIV test results of infants born to HIV
      infected mothers were tracked for nine years. In addition, chart audits were
      conducted on all patients to ensure that testing and counseling were documented
      for every pregnant woman who delivered at the hospital. RESULTS: From 1996 to
      2005, among 434 births to HIV-infected women enrolled in the clinic, only one HIV
      infected infant was born. Chart audits revealed that HIV testing and counseling
      were not being performed and/or documented by all physicians. Therefore, in
      service training was initiated for providers on a regular basis. In addition,
      other factors were addressed to aid patient adherence to treatment. DISCUSSION:
      The initiative's success in virtually eliminating perinatal transmission has had
      a major impact in reducing rates of pediatric HIV/AIDS for the community.

PMID- 17441556
TI  - Building a system of perfect depression care in behavioral health.
AB  - BACKGROUND: Depression, a common, serious disorder, may result in suicide in up
      to 10% of afflicted persons. METHODS: In 2001, the Division of Behavioral Health
      Services of the Henry Ford Health System (Detroit) launched an initiative to
      completely redesign depression care delivery using the Six Aims and the Ten Rules
      from the Institute of Medicine report Crossing the Quality Chasm. This "Perfect
      Depression Care" initiative, whose key goal was the elimination of suicide,
      entailed performance improvement activities in four domains-partnership with
      patients, clinical care (planned care model), access, and information flow.
      RESULTS: The rate of suicide in the patient population decreased by 75% (p =
      .007), from approximately 89 per 100,000 at baseline (2000) to approximately 22
      per 100,000 for the four-year follow-up interval (the average rate for 2002
      2005). DISCUSSION: This sustained reduction in suicide rate suggests that the
      process improvements implemented as part of the Perfect Depression Care
      initiative substantially improved the care of persons with depression. The
      initiative is the prototype for a comprehensive redesign of behavioral health
      care. Work is under way to "perfect" the care of persons with anxiety or
      psychotic disorders, and similar care systems are being developed for violence
      prevention and medication safety, with a particular focus on perfecting
      communication between providers. Pursuing perfection is no longer a project or
      initiative but a principle driving force embedded in the fabric of our care.

PMID- 17441557
TI  - Creating a continuum of care for chronically underserved children.
AB  - BACKGROUND: Grandfather Home for Children, a nonprofit residential treatment
      center in North Carolina, serves children with histories of abuse who exhibit
      sexual behavior problems and acute physical aggression. In June 2000, it launched
      an initiative to create placement resources for children who had been identified
      as chronically underserved-foster care, adoption services, and other appropriate
      community services. METHODS: A total of 638 children served by Grandfather Home
      for Children were included in this study. The data were collected during a six
      year period (October 1999-September 2005). The data to assess the agency's goals
      was collected through the agency's general performance indicators that are
      gathered on a quarterly and yearly basis, based on the agency's fiscal year.
      Performance improvement activities included substantive changes in
      administrative, staffing, training, and information systems. RESULTS: Between
      1999 and 2005 the agency's initiative achieved a 342% increase in the number of
      children it was able to serve, a 33% decrease in the average length of stay for
      children in care and a 721% increase in the percentage of children served in
      their home community, and 100% of the foster children had two or fewer
      placements. DISCUSSION: The initiative to create a continuum of care has enabled
      the agency to successfully provide step-down opportunities and serve more
      children in the least restrictive environment for a shorter period of time with
      fewer placement changes than observed in comparative statistics at both the
      federal or state level.

PMID- 17441558
TI  - Improving pediatric immunization rates in a safety-net delivery system.
AB  - BACKGROUND: Denver Community Health Services (DCHS)' goal was to increase
      childhood immunization rates in the high-risk pediatric patient population served
      through its safety-net delivery system. The specific goal of the initiative was
      to ensure that children younger than 3 years of age with at least one primary
      care visit received all recommended vaccines by 24 months of age. METHODS: An
      immunization registry was developed to accurately track patients, regular
      assessment of immunization levels were conducted with provision of clinic
      specific feedback, and team-based quality improvement meetings were held. The
      computerized immunization registry assisted in implementing all the remaining
      improvement activities. For example, improvement of on-time delivery of vaccines
      in primary care clinics was accomplished through a rules engine in the vaccine
      registry, standing orders for vaccine delivery, and implementation of vaccine
      delivery protocols that eliminated missed opportunities. RESULTS: From 1995 to
      2006, Denver Community Health documented a 47% increase in immunization rates for
      2-year-old patients and a 26% increase for 1-year-old-patients. Two-year-old
      immunization rates exceeded 85% by the end of this time period. DISCUSSION: The
      initiative improved pediatric immunization rates with demonstrated sustainability
      during a 10-year period. Success is attributed to staff commitment to process
      improvement activities and use of a patient registry for pediatric immunization
      delivery.

PMID- 17441559
TI  - Providing timely access to care: what is the right patient panel size?
AB  - BACKGROUND: Delays for appointments are prevalent, resulting in patient
      dissatisfaction, higher costs, and possible adverse clinical consequences. A
      "just-in-time" approach to patient scheduling, called advanced access, has been
      effective in reducing delays in multiple clinical settings. Offering most
      patients appointments on the same day requires achieving an appropriate balance
      between supply of and demand for appointments, but no methods have been
      previously proposed to determine what this balance should be. METHODS: A measure
      of balance is termed the overflow frequency level--the fraction of days when
      demand exceeds the average number of appointment slots available. A probability
      model was developed to estimate this measure for any practice. The model can be
      used in identifying an appropriate panel size or, conversely, the physician
      capacity needed to provide timely access. RESULTS: Delays for appointments will
      be excessive unless the ratio of the average daily demand for appointments to the
      average daily capacity is less than one. This ratio's appropriate value is
      dependent on the desired overflow frequency level, which indicates the fraction
      of days for which physician overtime would be necessary to offer most patients
      same-day appointments. A table provides suggested panel sizes for a range of
      practice types, and a spreadsheet file is available on request to help determine
      panel size or physician capacity in any specific situation. CONCLUSION: The
      simple probability model can be used to improve the timeliness of care while
      considering the constraints on physicians' working hours.

PMID- 17441560
TI  - Implementing a ventilator bundle in a community hospital.
AB  - BACKGROUND: Mercy & Unity Hospitals of Minnesota implemented the ventilator
      bundle concept as part of an Institute for Healthcare Improvement (IHI)
      collaborative on improving care in the intensive care unit (ICU). METHODS: The
      two hospitals, which function as a single hospital, have a total of 450 beds, and
      each has a 20-bed ICU. The IHI bundle was composed of (1) head-of-bed elevation,
      (2) a daily "sedation vacation" along with a readiness-to-wean assessment, (3)
      peptic ulcer disease prophylaxis, and (4) deep vein thrombosis prophylaxis.
      Additional interventions likely complementary to the ventilator bundle were a
      hand hygiene campaign and an oral care protocol. RESULTS: Overall compliance with
      the four bundle elements reached 100% by January 2004. At the end of the
      collaborative, Mercy's VAP rate decreased from 6.1 to 2.70 per 1000 ventilator
      days, and Unity's VAP rate decreased from 2.66 to 0 per 1000 ventilator days.
      DISCUSSION: The all-or-none nature of the bundle may have helped
      multidisciplinary staff members perceive the project as a systemic change versus
      a one-time intervention. Staff members needed to implement both structural
      changes, such as preprinted order sets for ventilator management and sedation,
      and cultural changes, such as increased collaboration with respiratory therapy.
      CONCLUSION: The decrease in VAP provides a promising example of the potential of
      intervention techniques and bundle implementation in a community hospital.

PMID- 17441561
TI  - Putting evidence-based clinical practice guidelines into practice: an academic
      pediatric center's experience.
AB  - BACKGROUND: Clinical practice guidelines can provide a much-needed interface
      between research and practice, pointing the way to higher quality, evidence
      based, and more cost-effective care. Cincinnati Children's Hospital Medical
      Center developed a formal process for the production of 29 evidence-based
      guidelines and companion tools. COMPONENTS OF DEVELOPMENT AND IMPLEMENTATION:
      Clinical practice guidelines and their companion documents are developed by
      interprofessional teams that are led by community physicians and that include
      hospital-based physicians, nurses, other allied health professionals, and
      patients or parents. An education coordinator develops an education plan that
      outlines specific clinical practice changes and expected outcomes to be
      monitored. Guideline evidence is embedded into companion documents and processes
      available at the point of care. Electronic order sets for treatments and
      medications have been developed using available guidelines as sources of
      evidence. All guideline-based order sets include an automatic order for use of
      the associated clinical pathway. It is important to create and maintain an
      evidence-based environment in an academic medical center. CONCLUSIONS: Keys to
      success include a rigorous methodology, tools that place the evidence in the
      hands of providers at the site of care, feedback on outcomes, and an environment
      that encourages evidence-based care.

PMID- 17441562
TI  - A pediatric medical emergency team manages a complex child with hypoxia and
      worried parent.
AB  - As demonstrated in this case report, parental concern can serve as an important
      and effective call trigger.

PMID- 17441564
TI  - [Cardiogenetics: the importance of identifying patients with hereditary heart
      disease].
AB  - During the past decade, developments in the field of DNA diagnostics have
      resulted in the confirmation of the genetic nature of several cardiac diseases.
      In a cardiogenetics outpatient clinic, a cardiologist and a clinical geneticist
      together evaluate persons with a (possible) hereditary cardiac disease. It is of
      utmost importance that patients with hereditary cardiac diseases be recognised
      and subsequently referred for genetic counselling as several preventive and
      therapeutic options are available.

PMID- 17441563
TI  - [Three previously healthy persons with a stress fracture].
AB  - A 42-year-old man presented with a one-month history of pain in his left knee,
      due to a fracture of the left medial tibia plateau, following a footrace. A 24
      year-old man, also a jogger, had had increasing pain in his right lower leg for 4
      months, which turned out to be due to a fracture of the posteromedial border of
      the tibia at the insertion of the flexor digitorum longus muscle. A 35-year-old
      woman presented with pain in her left foot and ankle that was due to a march
      fracture of the second metatarsal bone after over 5 hours of intermittent use of
      the clutch in a traffic jam. In all 3 patients, temporary cessation of the
      causative activity was sufficient for complete recovery after 3 months. Stress
      fractures are easily missed on X-rays. Treatment is conservative and consists of
      the elimination of causative factors to allow adequate healing. In selected
      cases, a splint or brace may be indicated. Furthermore, certain high risk and
      displaced fractures should be considered for surgical fixation. Return to the
      causative activity should be gradual with attention being paid to other potential
      risk factors.

PMID- 17441565
TI  - [Diagnosis and treatment of bipolar disorder in children].
AB  - In general, bipolar disorder with its classical presentation of regularly
      recurring manic and depressive episodes can be well diagnosed in adults and
      adolescents. However, bipolar disorder in children is a controversial issue,
      difficult to diagnose and to distinguish from other illnesses that frequently
      occur in childhood. In the US, where the diagnosis of'bipolar disorder' is made
      relatively often in children, not only its classical presentation but also
      chronic mood dysregulation and even other mood symptoms may lead to the diagnosis
      of bipolar disorder. The preferred view is the British one, whereby bipolar
      disorder is only diagnosed in children if they present with clear manic episodes
      and euphoric mood. Treatment of bipolar disorder in children consists of
      pharmacotherapy and of psychoeducation aimed at lifestyle adjustments, including
      reduction of stress, a stable sleep pattern, and adjustments at school.

PMID- 17441566
TI  - [Wound healing in venous ulcers; mechanisms, approach and modern developments].
AB  - A large proportion of the population, particularly the elderly, suffer from
      venous insufficiency which regularly leads to the development of leg ulcers.
      Delayed wound healing is a major problem in ulcers making them a target for both
      conventional and newly developed advanced therapies. Good compression therapy and
      wound cleansing are essential for wound healing. A number of advanced local
      application therapies are currently being developed that are aimed particularly
      at the 'hard-to-heal' group. These therapies include the application of tissue
      engineered skin substitutes.

PMID- 17441567
TI  - [Diagnostic image (315). A mentally retarded woman with facial skin lesions].
AB  - A 20-year-old African woman had mental retardation and multiple fibromatous
      facial skin lesions caused by tuberous sclerosis complex.

PMID- 17441568
TI  - [Ancillary diagnostic imaging is useful if there is atypical evidence of
      appendicitis].
AB  - Patients with an atypical presentation of acute appendicitis may benefit from
      ancillary diagnostic imaging, especially CT. The literature shows a decrease of
      the number of negative appendectomies with this approach, and other causes are
      diagnosed in about one third of the patients. In addition, costs were reduced.
      Ultrasonography is a good alternative in pregnant women and in women with
      suspected gynaecological pathology.

PMID- 17441569
TI  - [Ancillary diagnostic imaging is undesirable if there is evidence of
      appendicitis].
AB  - CT and ultrasound have been advocated to improve the diagnostic accuracy and
      management of appendicitis. However, these were single-centre studies, performed
      by specialised radiologists and with a low level of evidence. Most of the
      literature shows no increase in diagnostic accuracy or decrease of negative
      appendectomies if radiographic imaging techniques are applied. However these
      techniques do lead to disadvantages such as radiation load and unnecessary
      prolongation of the diagnostic phase. Therefore, CT or ultrasound are of no use
      in the diagnosis and management of acute appendicitis.

PMID- 17441570
TI  - [Genetic identification of patients and families with a long-QT syndrome: large
      regional differences in the result of 10 years].
AB  - OBJECTIVE: To determine the pattern of referral of Dutch patients with a long-QT
      syndrome (LQTS) on the basis of the postal codes of the LQTS probands from whom
      blood samples were submitted for DNA diagnostics. DESIGN: . Retrospective cohort
      study. METHOD: From the databases that are coupled to DNA diagnostics, all index
      patients were included for whom LQTS diagnostics had been requested during the
      period 1996-2005 at two clinical genetics centres (the University Medical Centre
      in Amsterdam and Maastricht University Hospital). The results were related to the
      postal code of the referred patient and corrected for the number of inhabitants
      of the region concerned. RESULTS: A total of 421 potential LQTS probands were
      included. Corrected for the numbers of inhabitants in the various postal codes,
      the number of referrals varied from 3 per million to 110 per million inhabitants.
      In view of the most recent estimated prevalence of LQTS (1:2000), this means that
      only 15% ofthe carriers of the LQTS mutation have so far been detected.
      CONCLUSION: There were large regional differences in the Netherlands in the
      requests for DNA diagnostics in patients with clinical LQTS. The overwhelming
      majority of the LQTS patients in the Netherlands have not yet been referred or
      identified. Expanding the available courses for general practitioners and
      cardiologists that are given by the staff of the cardiogenetic centres would seem
      to be indicated.

PMID- 17441571
TI  - [An 80-year-old woman with dyspnoea caused by cardiac myxoma].
AB  - An 80-year-old woman presented with general malaise and dyspnoea that has
      persisted for 2 months. Physical examination, laboratory tests, chest X-ray and
      ECG were normal, but tachycardia was not. A CT scan of the thorax performed due
      to suspicion of pulmonary embolism revealed a lesion in the right atrium and no
      other abnormalities. Echocardiography confirmed the presence of the tumour and
      also showed pulmonary hypertension. Cardiac myxoma was considered and the tumour
      was surgically removed. The patient recovered completely but the dyspnoea
      persisted. Cardiac myxoma is often difficult to confirm. Clinical presentation of
      a myxoma is determined by its location, size and mobility. Symptoms are a result
      of mechanical obstruction, embolism or constitutional effects. Treatment consists
      of surgical removal of the myxoma due to the associated risk of embolism and
      sudden death.

PMID- 17441572
TI  - [Biographies about the chief editors of the Dutch Journal of Medicine in the past
      150 years].
AB  - The Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine) possesses
      painted portraits of all of its former editors-in-chief. Few people remember
      these physicians or their significance to the journal. This year marks the 150th
      jubilee year ofthe journal and provides an occasion to publish a series of 13
      brief biographies. According to the first historiographer, the motive for
      establishing the journal in 1856 was to unite the fragmented medical press into
      one high-quality medical and scientific journal. However, it may also have been
      an attempt by a group of reformist physicians, the so-called 'hygienists', to
      gain political and social influence so that they could realise their goal, which
      was to improve the standard ofliving and health of the general population.

PMID- 17441573
TI  - [Jacobus Penn, 'manager' of the Dutch Journal of Medicine 1857-1866].
AB  - Jacobus Penn (1821-1890) was a physician and hygienist who devoted himself to the
      improvement of public health. He was cofounder and board member of many
      organizations. He cofounded the Nederlandsch Tijdschrift voor Geneeskunde (Dutch
      Journal of Medicine) and acted as its first editor-in-chief from 1857 to 1866.
      Penn also contributed substantially to the new legislation on medical education
      in 1865, which unified training and exams on an academic level. In I866 he laid
      the foundation for the state health inspectorate and subsequently worked as an
      inspector for many years.

PMID- 17441574
TI  - [150th anniversary of the Vereniging Nederlands Tijdschrift voor Geneeskunde
      (Association Dutch Journal of Medicine)].

PMID- 17441575
TI  - [Varicella: previously healthy children sometimes develop complications].

PMID- 17441576
TI  - [An asymmetrical face due to torticollis in two young children].

PMID- 17441577
TI  - [Central congenital hypothyroidism due to Graves' disease in the mother].

PMID- 17441578
TI  - Comment on Y.-H. Hsu et al., "electrical and mechanical fully coupled theory and
      experimental verification of Rosen-type piezoelectric transformers" [see
      reference [1]].
AB  - This letter discusses the difference between piezoelectric constitutive relations
      for the case of one-dimensional stress and the case of one-dimensional strain,
      and its implications in the modeling of Rosen piezoelectric transformers.

PMID- 17441579
TI  - Electromechanical coupling coefficient k15 of polycrystalline ZnO films with the
      c-axes lie in the substrate plane.
AB  - The (1120) textured polycrystalline ZnO films with a high shear mode
      electromechanical coupling coefficient k15 are obtained by sputter deposition. An
      over-moded resonator, a layered structure of metal electrode film/(1120) textured
      ZnO piezoelectric film/metal electrode film/silica glass substrate was used to
      characterize k15 by a resonant spectrum method. The (1120) textured ZnO
      piezoelectric films with excellent crystallite c-axis alignment showed an
      electromechanical coupling coefficient k15 of 0.24. This value was 92% of k15
      value in single-crystal (k15 = 0.26).

PMID- 17441580
TI  - Precise trajectory tracking of a piezoactuator-driven stage using an adaptive
      backstepping control scheme.
AB  - In this paper, an adaptive backstepping control scheme is proposed for precise
      trajectory tracking of a piezoactuator-driven stage. Differential equations
      consisting of dynamics of a linear motion system and a hysteresis function are
      investigated first for describing the dynamics of motion of the piezoactuator
      driven stage with hysteresis behavior. Then, to identify the uncertain parameters
      designed in the differential equations, the Powell method of a numerical
      optimization technique is used. From the differential equations identified, an
      equivalent state-space model is developed, then a linear state-space model
      through a state transformation is established. In the linear state-space model,
      the hysteresis function is approximated by the first three terms of a Taylor
      series expansion. Based on the linear state-space model, we developed an adaptive
      backstepping control for the trajectory tracking. By using the proposed control
      approach to trajectory tracking of the piezoactuator-driven stage, improvements
      in the tracking performance, steady-state error, and robustness to disturbance
      can be obtained. To validate the proposed control scheme, a computer-controlled,
      single-axis piezoactuator-driven stage with a laser displacement interferometer
      was set up. Experimental results illustrate the feasibility of the proposed
      control for practical applications in trajectory tracking.

PMID- 17441581
TI  - Characteristic analysis and design of a B14 rotary ultrasonic motor for a robot
      arm taking the contact mechanism into consideration.
AB  - The ultrasonic motor (USM) has many merits for use in a robot arm application.
      Therefore, the disk-type traveling wave B14 rotary ultrasonic motor (RUSM) is
      proposed in this paper for that application. Up to the present time, the analysis
      and design of the USM have been almost always performed using rough analytic
      methods or using commercial analysis tools. As a result, it was impossible to
      achieve an exact analysis and design of the USM. In order to address this
      problem, this paper proposes the analysis and design methodology of the B14 RUSM
      using a numerical method (3-D FEM) combined with an analytic method taking the
      contact mechanism into consideration in a linear operation. This methodology is
      applicable to many other kinds of USMs that use similar mechanisms. In addition,
      the mechanical system and the driving circuit of the B14 RUSM are designed and
      prototyped. Finally, the proposed analysis and design methodology is validated by
      comparing its outcomes with the experimental data. Also, the appropriateness of
      the suggested RUSM for the application of a robot arm was verified.

PMID- 17441582
TI  - Design and metrological features of microwave synthesizers for atomic fountain
      frequency standard.
AB  - In this paper we describe the improved redesign of the microwave frequency
      synthesizers for Laboratoire National d'Essais-Systemes de Reference Temps-Espace
      (LNE-SYRTE) atomic fountains. The synthesizers use a cryogenic oscillator to
      generate both Cs and Rb hyperfine frequencies based on a new distribution
      frequency of 1 GHz. The main metrological features (phase noise, long-term phase
      stability, and spectral purity) of the synthesizers have been measured in situ
      connected to an atomic fountain and are compatible with an accuracy goal of 10(
      16) for the atomic fountains. The simultaneous test of two different synthesizers
      on the FO2 atomic fountain at the 10(-16) level also is reported.

PMID- 17441583
TI  - Noise properties of microwave signals synthesized with femtosecond lasers.
AB  - We discuss various aspects of high resolution measurements of phase fluctuations
      at microwave frequencies. This includes methods to achieve thermal noise limited
      sensitivity, along with the improved immunity to oscillator amplitude noise. A
      few prototype measurement systems were developed to measure phase fluctuations of
      microwave signals extracted from the optical pulse trains generated by
      femtosecond lasers. This enabled first reliable measurements of the excess phase
      noise associated with optical-to-microwave frequency division. The spectral
      density of the excess phase noise was found to be -140 dBc/Hz at 100 Hz offset
      from the 10 GHz carrier which was almost 40 dB better than that of a high quality
      microwave synthesizer.

PMID- 17441584
TI  - PSF dedicated to estimation of displacement vectors for tissue elasticity imaging
      with ultrasound.
AB  - This paper investigates a new approach devoted to displacement vector estimation
      in ultrasound imaging. The main idea is to adapt the image formation to a given
      displacement estimation method to increase the precision of the estimation. The
      displacement is identified as the zero crossing of the phase of the complex cross
      correlation between signals extracted from the lateral direction of the
      ultrasound RF image. For precise displacement estimation, a linearity of the
      phase slope is needed as well as a high phase slope. Consequently, a particular
      point spread function (PSF) dedicated to this estimator is designed. This PSF,
      showing oscillations in the lateral direction, leads to synthesis of lateral RF
      signals. The estimation is included in a 2-D displacement vector estimation
      method. The improvement of this approach is evaluated quantitatively by
      simulation studies. A comparison with a speckle tracking technique is also
      presented. The lateral oscillations improve both the speckle tracking estimation
      and our 2-D estimation method. Using our dedicated images, the precision of the
      estimation is improved by reducing the standard deviation of the lateral
      displacement error by a factor of 2 for speckle tracking and more than 3 with our
      method compared to using conventional images. Our method performs 7 times better
      than speckle tracking. Experimentally, the improvement in the case of a pure
      lateral translation reaches a factor of 7. Finally, the experimental feasibility
      of the 2-D displacement vector estimation is demonstrated on data acquired from a
      Cryogel phantom.

PMID- 17441585
TI  - Direct comparison of feature tracking and autocorrelation for velocity
      estimation.
AB  - Feature tracking is an algorithm for estimating tissue motion and blood flow
      using pulse-echo ultrasound. It was proposed as a computationally simpler
      alternative to other techniques such as autocorrelation and time-domain cross
      correlation. The advantage of feature tracking is that it selectively extracts
      easily identifiable parts of the speckle signal (e.g., the local maxima),
      reducing the amount of information being processed. Studies on feature tracking
      to date have used stationary, speckle-generating targets to simulate blood flow.
      Also, feature tracking has not been compared with accepted commercial methods.
      This study directly compares feature tracking performance with the complex
      autocorrelation method, which is the most common color flow algorithm.
      Experiments were performed with both a rotating string phantom and a commercial
      flow phantom surrounded by tissue-mimicking material, using 2.25 MHz and 3.5 MHz
      transducers, under more realistic signal-to-clutter (-15 to -35 dB) and signal-to
      noise ratios (SNR) (15 dB to 3 dB) than previous translating-phantom tests. The
      feature tracking approach is shown to produce mean estimates comparable to
      autocorrelation (R2 = 0.9954 and 0.9960 for 6-sample and 12-sample
      autocorrelation, respectively, and R2 = 0.9998 for both 6-sample and 12-sample
      feature tracking) for velocities ranging from 10 to 100 cm/s. The variance of
      feature-tracking estimates is shown to compare favorably to the complex
      autocorrelation approach using the same number of ensemble flow samples (19 to
      28% lower standard deviation for 3.5 MHz, 36 to 55% lower standard deviation for
      2.25 MHz). However, linear regression of the feature locations does not produce
      an appreciable improvement in estimation variance. Discussion of the need for
      further research, particularly in the areas of feature detection and feature
      correspondence, is given.

PMID- 17441586
TI  - Bandwidth and resolution enhancement through pulse compression.
AB  - A novel pulse compression technique is developed that improves the axial
      resolution of an ultrasonic imaging system and provides a boost in the echo
      signal-to-noise ratio (eSNR). The new technique, called the resolution
      enhancement compression (REC) technique, was validated with simulations and
      experimental measurements. Image quality was examined in terms of three metrics:
      the eSNR, the bandwidth, and the axial resolution through the modulation transfer
      function (MTF). Simulations were conducted with a weakly-focused, single-element
      ultrasound source with a center frequency of 2.25 MHz. Experimental measurements
      were carried out with a single-element transducer (f/3) with a center frequency
      of 2.25 MHz from a planar reflector and wire targets. In simulations, axial
      resolution of the ultrasonic imaging system was almost doubled using the REC
      technique (0.29 mm) versus conventional pulsing techniques (0.60 mm). The -3 dB
      pulse/echo bandwidth was more than doubled from 48% to 97%, and maximum range
      sidelobes were -40 dB. Experimental measurements revealed an improvement in axial
      resolution using the REC technique (0.31 mm) versus conventional pulsing (0.44
      mm). The -3 dB pulse/echo bandwidth was doubled from 56% to 113%, and maximum
      range sidelobes were observed at -45 dB. In addition, a significant gain in eSNR
      (9 to 16.2 dB) was achieved.

PMID- 17441587
TI  - Cystic resolution: a performance metric for ultrasound imaging systems.
AB  - This paper describes a metric that can be used to characterize the resolution of
      arbitrary broadband coherent imaging systems. The metric is particularly suited
      to medical ultrasound because it characterizes scanner performance using the
      contrast obtained by imaging anechoic cysts of various sizes that are embedded in
      a speckle-generating background, accounting for the effect of electronic noise.
      We present the theoretical derivation of the metric and provide simulation
      examples that demonstrate its utility. We use the metric to compare a low-cost,
      handheld, C-scan system under development in our laboratory to conventional
      ultrasound scanners. We also present the results of simulations that were
      designed to evaluate and optimize various parameters in our system, including the
      f/# and apodization windows. We investigate the impact of electronic noise on our
      system and quantify the tradeoffs associated with quantization in the analog to
      digital converter. Results indicate that an f/1 receive aperture combined with 10
      bit precision and a signal-to-noise ratio (SNR) of 0 dB per channel would result
      in adequate image quality.

PMID- 17441588
TI  - A novel phase assignment protocol and driving system for a high-density focused
      ultrasound array.
AB  - Currently, most phased-array systems intended for therapy are one-dimensional (1
      D) and use between 5 and 200 elements, with a few two-dimensional (2-D) systems
      using several hundred elements. The move toward lambda/2 interelement spacing,
      which provides complete 3-D beam steering, would require a large number of
      closely spaced elements (0.15 mm to 3 mm). A solution to the resulting problem of
      cost and cable assembly size, which this study examines, is to quantize the
      phases available at the array input. By connecting elements with similar phases
      to a single wire, a significant reduction in the number of incoming lines can be
      achieved while maintaining focusing and beam steering capability. This study has
      explored the feasibility of such an approach using computer simulations and
      experiments with a test circuit driving a 100-element linear array. Simulation
      results demonstrated that adequate focusing can be obtained with only four phase
      signals without large increases in the grating lobes or the dimensions of the
      focus. Experiments showed that the method can be implemented in practice, and
      adequate focusing can be achieved with four phase signals with a reduction of 20%
      in the peak pressure amplitude squared when compared with the infinite-phase
      resolution case. Results indicate that the use of this technique would make it
      possible to drive more than 10,000 elements with 33 input lines. The
      implementation of this method could have a large impact on ultrasound therapy and
      diagnostic devices.

PMID- 17441589
TI  - Influence of surface roughness of Bragg reflectors on resonance characteristics
      of solidly-mounted resonators.
AB  - The solidly mounted resonator (SMR) is fabricated using planar processes from a
      piezoelectric layer sandwiched between two electrodes upon Bragg reflectors,
      which then are attached to a substrate. To transform the effective acoustic
      impedance of the substrate to a near zero value, the Bragg reflectors are
      composed of alternating high and low acoustic impedance layers of quarter
      wavelength thickness. This paper presents the influence of Bragg reflector
      surface roughness on the resonance characteristics of an SMR. Originally, an
      A1N/A1 multilayer is used as the Bragg reflector. The poor surface roughness of
      this Bragg reflector results in a poor SMR frequency response. To improve the
      surface roughness of Bragg reflectors, a molybdenum (Mo)/titanium (Ti) multilayer
      with a similar coefficient of thermal expansion is adopted. By controlling
      deposition parameters, the surface roughness of the Bragg reflector is improved,
      and better resonance characteristics of SMR are obtained.

PMID- 17441590
TI  - Elastic waves in a fluid-loaded, semi-infinite axisymmetric rod.
AB  - In a fluid-loaded, semi-infinite axisymmetric rod, a free shear stress boundary
      condition on the circular cross-sectional end introduces complicated,
      nondispersive waves in the solid. They are composed of a pulse wave, which has
      the same waveform as the transmitted one and travels at speed c1, and different
      kinds of pulse trains, each of which travels along the rod at the speed of either
      c1 or square root of 2c2, where c1 and c2 are the propagating speeds of the
      longitudinal and transversal bulk waves, respectively. Furthermore, one can
      conclude from the solutions to the boundary conditions that c1 and square root of
      2c2 are the only phase speeds of nondispersive waves. Frequency equations
      associated with these waves are established, and the solutions are solved and
      discussed analytically and numerically. The acoustic field in the fluid is also
      fully discussed, and it is more complicated than a single outgoing Hankel
      function as described for an infinite rod. The acoustic energy coupling between
      the solid and the fluid and the end reflection and transmission are quantified as
      well. In the end, experimental examinations of the echo spectra, using an
      aluminum rod immersed in the water and air, fully confirm the numerical solutions
      to the frequency equations.

PMID- 17441591
TI  - Numerical calculation of the sound field focused by acoustic lens with an
      arbitrary axisymmetric sound speed distribution.
AB  - The expressions that describe the sound field focused by an acoustic lens with
      different sound speed distribution (SSD) in lens are given. Numerical calculation
      results are presented, in which the axial and lateral sound pressure
      distributions and the -3 dB sound beam profile along the focused field are given
      out for three types of the acoustic focused lens with revolving-arc curved outer
      surface and four types' axisymmetric SSD. It is shown that, when sound beam is
      focused by a lens with SSD, the best focal point moves away from the lens and
      achieves a large focal region compared with the no-SSD case. The maximum axial
      focused intensity at the best focal point is smaller than that of the no-SSD
      case, but the focused beam width at the best focal point is larger than that of
      the no-SSD case. The larger the coefficient of the SSD, the larger the focused
      beam width and the larger focal region, but the divergent angle is almost the
      same.

PMID- 17441592
TI  - Analysis of a rectangular ceramic plate in electrically forced thickness-twist
      vibration as a piezoelectric transformer.
AB  - A rectangular ceramic plate with appropriate electrical load and operating mode
      is analyzed for piezoelectric transformer application. An exact solution from the
      three-dimensional equations of linear piezoelectricity is obtained. The solution
      simulates the real operating situation of a transformer as a vibrating
      piezoelectric body connected to a circuit. Transforming ratio, input admittance,
      and efficiency of the transformer are obtained.

PMID- 17441593
TI  - Wooden panel paintings investigation: an air-coupled ultrasonic imaging approach.
AB  - In this paper, a method for the study of wooden panel paintings using air-coupled
      acoustical imaging is presented. In order to evaluate the advantages of the
      technique, several samples were made to mimic panel paintings along with their
      typical defects. These specimens were tested by means of both single-sided and
      through-transmission techniques using planar transducers. Image data were
      processed by means of a two-dimensional (2-D)-fast Fourier transform-based
      algorithm to increase the S/N ratio and 2-D representations (C-scans) were
      generated. The simulated defects were imaged using both configurations.
      Investigations were undertaken on four antique paintings from a private
      collection. The results presented and discussed in this investigation confirm
      both the robustness and the effectiveness of the technique in detecting defects
      such as delaminations and cracks in wooden panel paintings.

PMID- 17441594
TI  - Traveling-wave piezoelectric linear motor Part I: the stator design.
AB  - A new type of piezoelectric linear motor incorporating a traveling wave has been
      developed. The linear motor is comprised of a stator and a carriage. The stator
      design, which consists of a meander-line structure and gear teeth mounted on the
      meander-line structure, is the focus of this article. The meander-line structure
      is constructed with bimorph actuators arranged in a line. These actuators are
      driven by two phased sets of alternating current (ac) in order to generate a
      traveling wave. The traveling wave is transferred to the gear teeth, by which the
      carriage is driven. Modeling of the stator is derived by use of a strain energy
      method. The performance of various materials is evaluated by analytical and
      experimental methods. The analytical and the experimental results are quite
      approximate. Modal analysis is investigated using ANSYS. Appropriate modes
      associated with ultrasonic levels of resonant frequency are selected to obtain
      desired motion and to enhance the output performance. Surface speed for various
      applied input voltage are studied and indicate a nearly linear relationship. The
      stator in combination with the carriage makes up the linear motor.

PMID- 17441595
TI  - Traveling-wave piezoelectric linear motor part II: experiment and performance
      evaluation.
AB  - This article continues the discussion of a traveling-wave piezoelectric linear
      motor. Part I of this article dealt with the design and analysis of the stator of
      a traveling-wave piezoelectric linear motor. In this part, the discussion focuses
      on the structure and modeling of the contact layer and the carriage. In addition,
      the performance analysis and evaluation of the linear motor also are dealt with
      in this study. The traveling wave is created by stator, which is constructed by a
      series of bimorph actuators arranged in a line and connected to form a meander
      line structure. Analytical and experimental results of the performance are
      presented and shown to be almost in agreement. Power losses due to friction and
      transmission are studied and found to be significant. Compared with other types
      of linear motors, the motor in this study is capable of supporting heavier loads
      and provides a larger thrust force.

PMID- 17441596
TI  - Side radiation of Rayleigh waves from synchronous SAW resonators.
AB  - Surface acoustic wave (SAW) resonators on lithium tantalate (LiTaO3) and lithium
      niobate (LiNbO3) are investigated. The amplitude of the acoustic fields in the
      resonators are measured using a scanning laser interferometer. The amplitude
      profiles of the surface vibrations reveal the presence of distinct acoustic beams
      radiated from the transducer region of the SAW resonators and propagating with
      low attenuation. We suggest that this radiation is generated by the charges
      accumulating at the tips of the finger electrodes. The periodic system of
      sources, namely oscillating charges at the fingertips, generates Rayleigh-wave
      beams in the perpendicular and oblique directions. Green's function theory is
      used to calculate the coupling strength and slowness of the Rayleigh waves on 42
      degrees Y-cut LiTaO3 and Y-cut LiNbO3 substrates as a function of the propagation
      direction. Furthermore, the propagation angles of the Rayleigh-wave beams as a
      function of frequency are calculated. The computed angles are compared with the
      measured ones for both the LiTaO3 and LiNbO3 substrates.

PMID- 17441597
TI  - High-frequency surface acoustic waves excited on thin-oriented LiNbO3 single
      crystal layers transferred onto silicon.
AB  - The need for high-frequency, wide-band filters has instigated many developments
      based on combining thin piezoelectric films and high acoustic velocity materials
      (sapphire, diamond-like carbon, silicon, etc.) to ease the manufacture of devices
      operating above 2 GHz. In the present work, a technological process has been
      developed to achieve thin-oriented, single-crystal lithium niobate (LiNbO3)
      layers deposited on (100) silicon wafers for the fabrication of radio-frequency
      (RF) surface acoustic wave (SAW) devices. The use of such oriented thin films is
      expected to favor large coupling coefficients together with a good control of the
      layer properties, enabling one to chose the best combination of layer orientation
      to optimize the device. A theoretical analysis of the elastic wave assumed to
      propagate on such a combination of material is first exposed. Technological
      aspects then are described briefly. Experimental results are presented and
      compared to the state of art.

PMID- 17441598
TI  - Weakly nonlinear behavior of a plate thickness-mode piezoelectric transformer.
AB  - We analyzed the weakly nonlinear behavior of a plate thickness-shear mode
      piezoelectric transformer near resonance. An approximate analytical solution was
      obtained. Numerical results based on the analytical solution are presented. It is
      shown that on one side of the resonant frequency the input-output relation
      becomes nonlinear, and on the other side the output voltage experiences jumps.

PMID- 17441599
TI  - Mass sensitivity of thickness-twist modes in a rectangular piezoelectric plate of
      hexagonal crystals.
AB  - Mass sensitivity of thickness-twist vibration modes in a rectangular plate
      piezoelectric resonator of 6 mm crystals are obtained from the three-dimensional
      equations of linear piezoelectricity. The boundary conditions at the finite-plate
      boundaries all have been taken into consideration. The solutions obtained are
      exact, which is relatively few for piezoelectric problems over finite domains.
      The results are fundamental and useful to the understanding and design of
      piezoelectric resonators and acoustic wave sensors made of polarized ceramics,
      ZnO and AlN.

PMID- 17441600
TI  - Propagation of thickness-twist waves through a joint between two semi-infinite
      piezoelectric plates.
AB  - We study the propagation of thickness-twist waves through a joint between two
      semi-infinite piezoelectric plates of crystals with 6-mm symmetry or polarized
      ceramics. An exact solution from the three-dimensional equations of
      piezoelectricity is obtained. The solution shows the cutoff of certain waves and
      the presence of localized electromechanical fields near the joint. The results
      are of fundamental importance to the understanding and design of resonators and
      other devices made from plates of these materials, in particular thin film
      resonators of ZnO and AlN.

PMID- 17441601
TI  - Effects of electrodes with varying thickness on energy trapping in thickness
      shear quartz resonators.
AB  - We study the possibility of using electrodes of varying thickness for strong
      energy trapping in quartz thickness-shear resonators as an alternative for
      contoured resonators. A theoretical analysis is performed. Results show that
      nonuniform electrodes can produce strong trapping of thickness-shear modes.

PMID- 17441602
TI  - Sex and stem cell research.

PMID- 17441603
TI  - Shanghai University club uses technology to fight poverty.

PMID- 17441604
TI  - Machine learning in the life sciences.

PMID- 17441605
TI  - New criteria for selecting differentially expressed genes.
AB  - One of the major concerns in detecting changes in higher moments is these changes
      may be due to outliers or process errors that are not biologically significant.
      For example, a larger variance observed in the expression levels may simply due
      to the larger variation in the data collecting process. Several outliers, which
      exhibit some extreme expression levels than the rest of the samples, may also
      increase the variance or skewness of the expression levels significantly. So it
      is very important to reduce the effect of outliers and process errors by proper
      experimental designs [27], such as technical replicates and biological
      replicates, before high sensitivity criterion, such as ADS, can be applied. We
      have presented and demonstrated the operation of two new criteria, ADS and the
      MDS, for identifying differentially expressed genes. These two criteria were
      compared with several commonly used criteria, namely WTS, WRS, FCS, and ICE.
      Experiments with simulated data show ADS to be more powerful than the WTS. When
      high-sensitivity screening is required, ADS appears to be preferable to WTS. When
      an FPR similar to WTS is desired, MDS should be used. The popular Wilcoxon rank
      sum is a more conservative approach that should be employed when the lowest FPR
      is desired, even at the expense of lower TPRs. ICE is a less desirable criterion
      because it does not perform well for data generated by the normal model. FCS gave
      results similar to those of WTS. Evaluation of these algorithms using real
      biological datasets showed that ADS and MDS flagged several biologically
      significant genes that were missed by WTS, besides selecting most of the genes
      that are also selected by WTS.

PMID- 17441606
TI  - Using clinical information in goal-oriented learning.
AB  - We have proposed an extension to the Q-learning algorithm that incorporates the
      existing clinical expertise into the trial-and-error process of acquiring an
      appropriate administration strategy of rHuEPO to patients with anemia due to
      ESRD. The specific modification lies in multiple updates of the Q-values for
      several dose/response combinations during a single learning event. This in turn
      decreases the risk of administering doses that are inadequate in certain
      situations and thus increases the speed of the learning process. We have
      evaluated the proposed method using a simulation test-bed involving an
      "artificial patient" and compared the outcomes to those obtained by a classical Q
      learning and a numerical implementation of a clinically used administration
      protocol for anemia management. The outcomes of the simulated treatments
      demonstrate that the proposed method is a more effective tool than the
      traditional Q-learning. Furthermore, we have observed that it has a potential to
      provide even more stable anemia management than the AMP.

PMID- 17441607
TI  - Modeling the effects of toxins in metabolic networks.

PMID- 17441609
TI  - Automated heart abnormality detection using sparse linear classifiers.

PMID- 17441608
TI  - Multilabel associative classification categorization of MEDLINE articles into
      MeSH keywords.
AB  - The specific characteristic of classification of medical documents from the
      MEDLINE database is that each document is assigned to more than one category,
      which requires a system for multilabel classification. Another major challenge
      was to develop a scalable method capable of dealing with hundreds of thousand of
      documents. We proposed a novel system for automated classification of MEDLINE
      documents to MeSH keywords based on the recently developed data mining algorithm
      called ACRI, which was modified to accommodate multilabel classification. Five
      different classification configurations in conjunction with different methods of
      measuring classification quality were proposed and tested. The extensive
      experimental comparison showed superiority of methods based on reoccurrence of
      words in an article over nonrecurrent-based associative classification. The
      achieved relatively high value of macro F1 (46%) demonstrates the high quality of
      the proposed system for this challenging dataset. Accuracy of the proposed
      classifier, defined as the ratio of the sum of TP and TN examples to the total
      number of examples, reached 90%. Three scenarios were proposed based on the
      performed tests and different possible objectives. If a goal is to classify the
      largest number of documents, a configuration that maximizes micro F1 should be
      chosen. On the other hand, if a system is to work well for categories with a
      small number of documents, a configuration that maximizes macro F1 is more
      suitable. A tradeoff can be obtained by using a configuration that optimizes the
      average between macro and micro F1.

PMID- 17441610
TI  - Increasing the depth of anesthesia assessment.

PMID- 17441611
TI  - Epileptic seizure detection.

PMID- 17441612
TI  - A pattern recognition application framework for biomedical datasets.
AB  - Scopira facilitates the development of high-performance applications by providing
      many useful subsystems, flexible and efficient data models, low-level tools such
      as memory management and serialization, GUI constructs, high-level visualization
      modules, and the ability to implement parallel algorithms with MPI. Scopira plug
      in extensions have been developed to enable Matlab scripts to easily call any
      Scopira module, thus facilitating the migration of prototypes to highly efficient
      C++ applications. Scopira is continuously under development and future
      capabilities will include the ability to develop distributed programs using
      agents, applicable to grid-computing data mining applications. Scopira has proven
      to be a successful programming framework for implementing high-performance
      biomedical data analysis applications. It is based on C++, an efficient object
      oriented language, and the source code is available as an open-source project for
      other researchers to use and adapt to their own research endeavours. Scopira has
      been compiled to work on Linux and Windows XP operating systems with a port to
      the Mac OS under development. Scopira, EvIdent and RDP are freely available for
      download from www.scopira.org.

PMID- 17441613
TI  - A comprehensive human chromosome 21 database.

PMID- 17441614
TI  - Developing a modern web interface for database-driven bioinformatics tools.

PMID- 17441615
TI  - To do or not to do.

PMID- 17441616
TI  - Integrating orthodontics with restorative dentistry.
AB  - As restorative-cosmetic dentists, we have an obligation to deliver to our
      patients naturally appearing restorations supported by healthy gingival tissue
      and bone. Incorporating orthodontics into our comprehensive treatment planning
      will accomplish our goals and meet or exceed patient expectations. This article
      reviews some of the more common indications for pre-restorative (adjunctive)
      orthodontics.

PMID- 17441617
TI  - Expand your practice--adult expansion.
AB  - Adult expansion has always been a controversy. We will focus on three clinical
      cases with non-surgical adult expansion. These cases show the possibilities of
      improving smile esthetics without compromising function.

PMID- 17441618
TI  - Delayed extraction options with Tip-Edge technique.
AB  - Three patients are analyzed with multiple diagnostic techniques. The Tip-Edge
      technique is a combination of the mechanics of Begg and an improvement
      modification of the Edgewise bracket. It is shown to be advantageous in meeting
      esthetic objectives. A conservative treatment approach of non-extraction is
      preferred noting that extraction is an option midway through treatment if
      necessary.

PMID- 17441619
TI  - Occlusal cranial balancing technique.
AB  - The acronym for Occlusal Cranial Balancing Technique is OCB. The OCB concept is
      based on the architectural principle of a level foundation. The principles of
      Occlusal Cranial Balancing are a monumental discovery and if applied will enhance
      total body function.

PMID- 17441620
TI  - Class III non-surgical treatment: breaking the barrier.

PMID- 17441621
TI  - Excellence in orthodontics.

PMID- 17441622
TI  - Aren't we all made just the same?

PMID- 17441623
TI  - The Magnet philosophy: a prescription for nursing excellence.

PMID- 17441624
TI  - The effect of music therapy on patients' perception and manifestation of pain,
      anxiety, and patient satisfaction.
AB  - An extensive review and synthesis of current research was completed to identify
      the clinical benefit of using music therapy in the hospital setting. It
      demonstrated that music therapy has the potential to improve the hospital
      experience of patients.

PMID- 17441625
TI  - The evolution of nurse-to-nurse bedside report on a medical-surgical cardiology
      unit.
AB  - Change of shift report is unique to the nursing profession. During report, nurses
      transfer critical information to promote patient safety and best practices. Nurse
      to-nurse bedside report is described as a strategy that includes the patient in
      the reporting process and is an innovative alternative to traditional shift
      report.

PMID- 17441626
TI  - Engaging staff in the Magnet journey: the key is communication.
AB  - A Midwestern acute care facility shares its successful internal communication
      plan to engage stakeholders and describes its significance in achieving
      designation as a Magnet hospital. This plan remains a framework for ongoing
      communications toward sustaining a Magnet culture, completing annual interim
      reports, and preparing for redesignation in 4 years.

PMID- 17441627
TI  - Paving and resurfacing the road to Magnet: the perspective and wisdom of Magnet
      designated coordinators--part I.

PMID- 17441628
TI  - Paving and resurfacing the road to Magnet: devil in the details--part II.

PMID- 17441629
TI  - Paving and resurfacing the road to Magnet: part III--unique organizational
      characteristics.

PMID- 17441630
TI  - Vagus nerve stimulation: treatment modality for epilepsy.
AB  - Anticonvulsant medication is the golden standard for treatment of epilepsy. For
      patients who do not benefit sufficiently from anticonvulsants, vagal nerve
      stimulation using an implantable electrical nerve stimulator may be an option to
      reduce seizure frequency and intensity, thus improving patients' quality of life.
      The results of a series of vagus nerve stimulator implantations are described.

PMID- 17441631
TI  - Colorectal cancer: an overview of the epidemiology, risk factors, symptoms, and
      screening guidelines.

PMID- 17441632
TI  - Caring for a patient with HIV/AIDS.

PMID- 17441633
TI  - Anticoagulation therapy: reinforcing patient education.

PMID- 17441634
TI  - Supporting graduate nurse attainment of licensure.

PMID- 17441636
TI  - [Not Available].

PMID- 17441635
TI  - Beyond busyness: creating slack in the organization.
AB  - Human beings are not machines. The patient safety literature documents the price
      we pay for excessive overtime, long hours, and no breaks. Disengaged staff, high
      vacancy rates, and turnover are the products of cultures that do not support a
      professional environment where nurses are seen as knowledge workers. At his
      retirement dinner, a factory worker accepted accolades for his years of dedicated
      service. In his farewell speech, he noted that for 40 years the factory used his
      hands but never his brains. His expertise and knowledge were never acknowledged
      or solicited. Consequently he watched in silence for years as directives came
      down from managers and leaders that were totally unrealistic and bore no
      relevance to the reality in which he worked. And he watched the initiatives fail.
      Unfortunately we in health care can create that exact situation if we do not
      incorporate time (slack) into the schedules of our knowledge workers so they can
      unleash their genius, reinvent health care, and fix health care from the inside
      out. Nurse leaders must be the architects of participation and allow this to
      happen.

PMID- 17441637
TI  - [Not Available].

PMID- 17441638
TI  - [Not Available].

PMID- 17441639
TI  - [Not Available].

PMID- 17441640
TI  - [Not Available].

PMID- 17441641
TI  - [Not Available].

PMID- 17441642
TI  - [Not Available].

PMID- 17441643
TI  - [Not Available].

PMID- 17441644
TI  - [Not Available].

PMID- 17441645
TI  - [Not Available].

PMID- 17441647
TI  - [Not Available].

PMID- 17441646
TI  - [Not Available].

PMID- 17441649
TI  - [Not Available].

PMID- 17441648
TI  - [Not Available].

PMID- 17441650
TI  - [Not Available].

PMID- 17441651
TI  - Internal fixation of proximal humeral fractures.
AB  - We discuss the appropriate assessment and treatment options available for
      proximal humeral fractures. Important factors to consider are the fracture
      pattern, the bone quality and any co-morbidities. These are common injuries and
      are increasing in incidence due to an ageing population. The management of
      displaced 3- and 4-part fractures remains controversial. The ideal is anatomic
      reduction and stable internal fixation of the fractures especially the
      tuberosities to allow early mobilisation. The recent introduction of fixed angle
      locking plates allows stable fixation even in markedly osteoporotic bone. The
      early results are encouraging however there are presently no randomised trials
      comparing these devices to conservative treatment, conventional plating or
      hemiarthroplasty.

PMID- 17441652
TI  - History of radial head prosthesis in traumatology.
AB  - A review of the literature was performed to survey the history of the radial head
      prosthesis in traumatology. Radial head resection was the treatment of choice
      before Speed first reconstructed the radial head with a metal prosthesis. Over
      the years, the indication for the use of a radial head prosthesis changed from
      the prevention of heterotopic ossification to the prevention of proximal
      migration of the radius and instability of the elbow. Currently, the optimal
      indication for the use of radial head prostheses is a non-reconstructible radial
      head fracture with associated injuries that would leave the elbow, or forearm
      unstable if the radial head were resected.

PMID- 17441653
TI  - Adhesive shoulder capsulitis: does the timing of manipulation influence outcome?
AB  - The purpose of this study was to assess the influence of timing of manipulation
      under anaesthesia for adhesive capsulitis of the shoulder on the long-term
      outcome. One hundred and eighty consecutive patients with a diagnosis of adhesive
      capsulitis according to Codman's criteria were selected from a shoulder surgery
      database; 145 were available for follow-up after a mean period of 62 months
      (range: 12 to 125). All patients underwent manipulation under anaesthesia (MUA)
      with intra-articular steroid injection. A statistically significant improvement
      in range of movement, function (Oxford Shoulder Score) (OSS) and Visual Analogue
      pain intensity Score (VAS) was obtained following manipulation. Ninety percent of
      the 145 patients who successfully completed the study were satisfied with the
      procedure. Eighty-nine percent indicated that they would choose the same
      procedure again, if the same problem arose in the opposite shoulder. Eighty-three
      percent of the patients had manipulation performed less than 9 months from onset
      of symptoms (early MUA). The remainder had manipulation performed after 9-40
      months (late MUA). Patients who had early intervention had a significantly better
      Oxford Shoulder Score at final follow up; mobility and pain (VAS) were also
      letter than in the late group, but not significantly.

PMID- 17441654
TI  - Bicortical K-wires for distal radius fracture fixation: how many?
AB  - The aim of this study was to find out whether number and position of K-wires
      influence the stability of distal radius fractures treated by percutaneous wire
      fixation. Patients who underwent K-wire fixation for unstable fractures of the
      distal radius over a period of three years were included in this retrospective
      study. Radiographs taken immediately after the procedure and radiographs taken
      after removal of K-wires were analysed to study three radiological parameters:
      palmar or dorsal tilt, radial inclination and ulnar variance. Loss of these
      angles was analysed statistically against the number of wires (2 or 3) and
      position of wires (from radial styloid or a combination of styloid and dorsal
      wires). Ninety-five fractures were analysed with a mean age of 52.8 years and
      male to female ratio of 1:2. Average loss of radial inclination was 5.2 degrees,
      loss of palmar tilt was 8.3 degrees and loss of ulnar variance was 3.4 mm. Using
      3 wires or using a dorsal wire in addition to the styloid wires both improved the
      final radial length by 1.2 mm and 2 mm respectively, but the effects were
      statistically not significant. We found that the number or position of wires did
      not influence radiological outcome. Based on our findings we recommend the use of
      two K-wires: one from the radial styloid and one from the dorsal side for these
      fractures.

PMID- 17441655
TI  - Reliability of observer assessment of thermographic images in complex regional
      pain syndrome type 1.
AB  - This study aimed at evaluating the sensitivity, specificity, reliability and
      repeatability of observer assessment of thermographic images taken from Complex
      Regional Pain Syndrome (CRPS) type 1. A computer program was developed to let
      observers rate the difference between randomly presented thermographic images of
      pairs of hands of individuals. The sensitivity and specificity, and potential
      learning effects were measured. Effects of the colours and rank number of the
      images were analysed. The sensitivity was 71% and the specificity 85%. The
      repeatability was 0.5267 and the reliability was 0.4967. No significant relation
      was found between the rank number and the rating. There was a significant
      correlation between the colour pallet and the rating (r = 0.76). Although the
      colour pallet used partly explained the variance in the rating scores, this study
      shows that observer assessment of thermographic images may distinguish between
      CRPS1 patients and healthy controls. However, the reliability and repeatability
      of this assessment was rather low.

PMID- 17441656
TI  - Influence of labral tears on the outcome of acetabular augmentation procedures in
      adult dysplastic hips. Prospective assessment with a minimum follow-up of 12
      years.
AB  - Lesions of the acetabular labrum have been suspected to be one factor responsible
      for failures of Chiari osteotomy. We undertook a prospective investigation to
      adress this question. Twenty-six adult patients (mean age 34.5 years) with 26
      dysplastic hips were enrolled consecutively. All the hips studied showed
      arthritic changes. The labrum was inspected by arthroscopy during surgery (19
      shelf acetabuloplasties and 7 Chiari procedures). All hips were followed for a
      minimum of 12 years (12-14 years). Sixteen dysplastic hips (62%) were found to
      have labrum tears. Computed tomography (CT)-arthrography findings were similar to
      arthroscopic observations in 13 hips. Coxomety results showed that the acetabular
      roof angle (HTE), cervico-diaphyseal angle (CDA) and lateralisation were higher
      in cases with acetabular labral tears. On the other hand, the ventral center-edge
      angle (VCEA) was lower in hips with labral tears. During the follow-up period,
      eight hips which had undergone a Chiari osteotomy were converted to total hip
      replacement. Adult dysplastic hips are at risk for presenting labral tears.
      Clinical signs appear to have limited diagnostic value. Coxa valga, a small
      lateral center edge angle and a high acetabular roof angle were found in this
      study to be associated with a higher incidence of labral tears. Contrary to
      previous data reported in retrospective studies, the results of the present
      prospective investigation suggest that labral tears do not compromise the outcome
      of acetabulum enlargement procedures.

PMID- 17441657
TI  - External fixation of intertrochanteric fractures in elderly high-risk patients.
AB  - This study concerns 56 elderly high-risk patients with an intertrochanteric
      fracture of the femur, who were treated with the Citieffe/Ch-N external fixator
      between November 2002 and February 2004. A short intraoperative time (37
      minutes), no need for peroperative blood transfusion, fast mobilisation and a
      short hospitalisation (average 6 days, thus reducing the total cost) were noted.
      Union was obtained in all patients after 6 months. There was no significant
      difference between the functional status before the injury and at follow-up after
      12 months (p > 0.05). No deep pin track or wound infections occurred, but a
      superficial skin reaction was seen in 39.3%. The mortality rate was 16.1% at 6
      months, and 20.4% at 12 months, which contrasts favourably with other types of
      treatment. External fixation with this device can be used successfully for the
      treatment of elderly high-risk patients with intertrochanteric fractures.

PMID- 17441658
TI  - Navigated total knee arthroplasty: a radiological analysis of 42 randomised
      cases.
AB  - The purpose of this study was to evaluate the use of a navigation device in a
      cohort of 42 total knee arthroplasties (TKA). The patients were randomised into
      two groups. Total knee arthroplasties performed using the conventional technique
      formed the control group (21 knees); the experimental group included 21 knees
      performed with the aid of a computed navigation system. Postoperative mean values
      for the various measurements showed no significant difference in component
      alignment. However, the range of individual measurements for coronal and sagittal
      plane positioning was smaller in the navigated group, in which there were no
      outliers. Rotational alignment was not different between the two groups. This
      confirms the advantages and limitations of navigated TKA presented in larger
      studies.

PMID- 17441659
TI  - Medium-term results with the Press Fit Condylar (PFC) Sigma knee prosthesis the
      Wrightington experience.
AB  - The PFC Sigma total knee was introduced in 1997, incorporating a number of design
      changes. We report the mid-term results of a consecutive series of PFC Sigma knee
      arthroplasties performed between November 1997 and December 1998. Out of a total
      of 156 patients (166 knees), 5 patients (5 knees) were lost to follow-up and 6
      patients (6 knees) died of unrelated causes. This left 145 patients (155 knees),
      90 female and 55 male, with a mean age of 70 years (range, 53-88) and an average
      follow-up of 90 months (range, 84-96). Posterior cruciate retaining components
      were used in 136 knees (88%) and posterior-stabilized in 19 (12%). The patella
      was resurfaced in 74 (48%) knees. Follow-up was at 3, 6 and 12 months, then
      yearly. Preoperative American Knee Society and Oxford scores were compared with
      follow-up scores. The Knee Society radiological score was used for radiographic
      assessment. One knee (0.6%) was revised due to aseptic loosening. One knee (0.6%)
      had superficial wound infection, which settled with oral antibiotics. Two knees
      became deeply infected. Of these, one resolved following early debridement, the
      other developed chronic infection. Using revision for any reason as the end-point
      our cumulative success rate was 99.4%. The mean preoperative Knee score improved
      from 45 (30-65) to 84 (45-92), Functional score from 38 (25-55) to 73 (50-95) and
      Oxford score from 43 (33-52) to 17 (14-29). Radiographic review showed
      radiolucent lines in 54 (35%) tibial and 17 (11%) femoral components. The
      Radiological Knee Society score was less than 4 in all except one tibia where the
      score was 7. Our study shows excellent clinical results with the PFC Sigma total
      knee replacement after almost eight years follow-up.

PMID- 17441660
TI  - Early results with the new internal fixator systems LCP and LISS: a prospective
      study.
AB  - The Locking Compression Plate (LCP) and the Less Invasive Stabilisation System
      (LISS) are new implants with angular stability developed by the AO/ASIF. They
      offer an alternative for internal fixation in complex intra-articular fractures
      and high-energy diaphyseal fractures of the long bones. The new system was used
      in a prospective study to treat 113 patients (76 women, 37 men; average age: 53.1
      years) with 122 injuries (multifragment shaft fractures or complex intra
      articular, delayed/ non-union, malunion) from October 2002. Of these, 13 affected
      the humerus, 20 the radius, 2 the ulna, 21 the femur, 42 the tibia, 10 the
      fibula, 2 the acetabulum and 12 the calcaneus. Because of severe concomitant
      injuries, 18 fractures were first treated with an external fixator and
      definitively stabilised more than two weeks after the injury. Thirty-one patients
      were operated on after failure of other implants and non-union. Clinical and
      radiographic findings as well as complications were followed prospectively over a
      mean period of 20 months (range: 13 to 30). One patient was lost to follow-up. A
      total of 112 patients underwent a standardised follow-up examination. The outcome
      correlated with the severity of the fracture, anatomic reduction, adequate
      positioning of the plate and concomitant injuries. Despite the large number of
      open and comminuted fractures, no serious complications such as deep infections,
      vascular lesions, deep venous thrombosis or non-unions were noted. We found the
      new internal fixator system to be a safe and reliable procedure. It offers
      numerous fixation possibilities and has proven its value in complex fracture
      situations and in revision operations. A good knowledge of biomechanics is
      essential as well as precise preoperative planning.

PMID- 17441661
TI  - Free non-vascularised fibular graft for treatment of post-traumatic bone defects.
AB  - Post-traumatic bone defects usually occur from severe high-velocity injuries due
      to road traffic accidents; they may be difficult to fill. We have managed defects
      of long bones by the use of free non-vascularised fibular grafts harvested
      subperiosteally and held by screw fixation of the fibular strut ends to the ends
      of the bone defect, combined with an external fixator in 8 tibial defects and
      with a plate and screws in 2 ulnae and 2 humeri. Twelve patients, eleven male and
      one female, with a mean average age of 25 years (range 12-40), underwent this
      procedure. Eleven grafts (92%) united at both ends within an average of 4 months
      (range, 3 to 5 months). The defect lengths averaged 7 cm (range from 6 to 10 cm).
      The long-term follow-up showed complete 'tibialisation' of the fibula. Non
      vascularised fibular graft, compared to microvascular reconstruction and Ilizarov
      techniques, is a simple procedure that is still valid to bridge bone defects
      successfully in selected cases.

PMID- 17441662
TI  - The Ilizarov technique in joint contractures and dislocations.
AB  - This study was designed to evaluate the results of treatment of joint
      contractures (6 patients) and dislocations (2 cases) with an Ilizarov device. Six
      patients with restricting joint contractures were successfully treated and after
      gradual scar expansion they achieved a significant improvement in their range of
      motion. One patient with elbow instability after closed dislocation achieved 5
      degrees to 130 degrees of motion, while one patient with an open dislocation
      achieved a range of motion from 15 degrees to 100 degrees. These results suggest
      that a hinged Ilizarov external fixation frame can be a useful tool to restore
      function in such complex problems.

PMID- 17441663
TI  - Modified Essex-Lopresti / Westheus reduction for displaced intra-articular
      fractures of the calcaneus. Description of surgical technique and early outcomes.
AB  - We describe a modification of the classical Essex-Lopresti manoeuvre for the
      indirect reduction and stabilisation of displaced intra-articular fractures of
      the calcaneus. The radiological and functional results achieved using this
      technique in 15 patients is presented. Ten tongue-shaped and 8 joint depression
      type fractures were treated by the new method, incorporating the use of an
      additional traction pin. The pre and postoperative Bohler angles as well as the
      correction achieved were documented. Functional assessment was carried out using
      the Maryland Foot Score. The mean pre-operative Bohler angle in the joint
      depression group was 5.5 degrees, and in the tongue shaped fracture group 5
      degrees. The mean postoperative Bohler angle in the joint depression group was
      15.8 degrees, and in the tongue shape group was 23.25 degrees. At a mean follow
      up of 28 months the joint depression group scored 51/100 on the foot score, and
      the tongue shaped fracture group 77/100. The mean correction achieved as well as
      the mean overall functional scores were significantly better in the tongue shaped
      group. The technique described has much promise in the management of selected
      displaced intra-articular fractures of the calcaneus (true tongue shaped /
      Sanders II), and may also have a limited role in other fracture types in patients
      with significant co-morbidities, soft tissue compromise and poor healing
      potential.

PMID- 17441664
TI  - Rheumatoid forefoot reconstruction: 1st metatarsophalangeal fusion and excision
      arthroplasty of lesser metatarsal heads.
AB  - This is a retrospective review of 66 feet (mean follow-up of 3 years) in 43
      patients with painful severe rheumatoid forefoot deformities. All were treated by
      arthrodesis of the first metatarsophalangeal (MTP) joint through a dorsomedial
      incision and excision of the lesser metatarsal heads through a separate plantar
      approach. The mean post-operative AOFAS scores were 65.94 (range: 32 to 82). The
      mean post-operative Foot Function Index (FFI) was 0.47 (range: 0.23 to 0.63).
      Eighty five percent (57/67 feet) reported excellent or good pain relief, improved
      cosmetic appearance, and improved footwear comfort. The mean hallux valgus angles
      improved from 39 degrees to 16 degrees and the intermetatarsal angle from 16
      degrees to 8 degrees. Five feet had nonunion of the 1st MTP joint arthrodesis.
      There were five re-operations for non-union of the 1st MTP joint arthrodesis. The
      success of the operation as evidenced by this study depends upon attention to
      metatarsal length harmonisation, stabilisation of the 1st MTP joint and thereby
      even distribution of loading of the forefoot. The poor results in this study were
      as a result of a failure to secure the stability of the 1st MTP joint.

PMID- 17441665
TI  - Management of fibrous dysplasia. A report on 36 cases.
AB  - A consensus on the clinical course of fibrous dysplasia has not yet emerged in
      the literature. We retrospectively evaluated 36 patients who were diagnosed with
      fibrous dysplasia in our institution and were followed for a mean duration of
      56.5 months (range 7-210 months). Their mean age was 25.8 years (range 5-67
      years); 46.7% were male. The most frequent presenting complaints were pain (66%
      of patients) and pathological fracture (20%). Osteosarcoma developed in one
      patient 20 years after he had undergone radiation therapy for fibrous dysplasia
      in the tibia. Mazabraud syndrome was encountered in two patients, and aneurysmal
      bone cyst associated with fibrous dysplasia was seen in one patient. Fibrous
      dysplasia is generally considered a static disease, but with long-term follow-up
      it is found to have a more dynamic nature. For this reason, patients with fibrous
      dysplasia should be followed carefully over the long-term.

PMID- 17441666
TI  - Treatment of deep wound infections after spinal fusion with a vacuum-assisted
      device in patients with spinal cord injury.
AB  - Postoperative wound infection is a severe complication after spinal
      instrumentation, especially in a patient with spinal injury. We used vacuum
      assisted wound closure (VAC) in two patients with spinal cord injury, who
      presented deep wound infection after spinal instrumentation and were treated with
      an aggressive irrigation and debridement procedure. Three and four weeks after
      VAC application, the hardware was completely covered by granulation tissue and a
      secondary closure was undertaken. No significant complications were observed. Six
      months after secondary closure, the wounds remained healed, no signs of
      instrumentation loosening, haloing or lysis around the instrumentation were
      observed, and patients had completed their rehabilitation program and were
      discharged from hospital. Vacuum assisted wound closure appears as an excellent
      option in the treatment of deep wound infections after spinal instrumentation in
      patients with spinal cord injury.

PMID- 17441667
TI  - Glenoid osteolysis after arthroscopic labrum repair with a bioabsorbable suture
      anchor.
AB  - Bioabsorbable suture anchors are commonly used for arthroscopic repair of rotator
      cuff and labrum lesions. They provide soft-tissue attachment to bone. They have
      been introduced to avoid complications such as artefacts on MRI scans, commonly
      seen with metal anchors. However, bioabsorbable implants may lead to other
      problems such as local osteolysis, cyst formation, soft tissue inflammation and
      release of implant fragments into the joint space. The author describes the case
      of a professional female volleyball player, who presented osteolysis of the
      superior pole of the glenoid after arthroscopic repair of a SLAP lesion with a
      PLLA suture anchor. This is the first reported case of glenoid osteolysis after
      arthroscopic insertion of a bioabsorbable suture anchor. The author feels that
      the cause of osteolysis was a biological response to mechanical stress.

PMID- 17441668
TI  - Flexor tendon synovitis of the hand as first manifestation of atypical
      tuberculosis.
AB  - We present the case of a 73-year old patient suffering from chronic flexor tendon
      synovitis of the wrist with carpal tunnel syndrome. He underwent synovectomy and
      median nerve release. Primary bacteriology was negative. Histology of the excised
      synovia revelead non-caseating granuloma as typical for sarcoidosis. Further
      screening for sarcoidosis was negative. Culture of a sample harvested from the
      poorly healing wound was finally positive for Mycobacterium tuberculosis.
      Tuberculostatic treatment was started and the wound gradually healed. To the best
      of our knowledge, this is the first reported case of atypical non-caseating and
      sarcoidosis-like granulomas of the flexor tendon synovia of the hand as first
      manifestation of tuberculosis.

PMID- 17441669
TI  - Sleeve fracture of the upper pole of the patella: a case report.
AB  - Sleeve fractures of the upper pole of the patella in children are rare; only 2
      cases have been reported in the English literature and 1 case in the German
      literature. We present a case of this unusual lesion in order to stress the
      importance of being aware of the existence of upper pole sleeve fractures of the
      patella. We review the literature and we describe the symptoms, the clinical and
      radiological signs and the treatment. The diagnosis may be missed, the treatment
      is relatively simple and rewarding, and un- or mistreating this fracture leads to
      permanent disability.

PMID- 17441671
TI  - Early removal of a Maverick disc prosthesis: surgical findings and morphological
      changes.
AB  - We report the case of a patient who underwent explantation of a Maverick total
      disc prosthesis at the L5S1 level because of severe persisting pain one year
      after initial implantation. Dynamic radiographic imaging studies showed good
      position and size of the prosthesis and no evidence of loosening.
      Intraoperatively residual mobility at the proximal bone-prosthesis interface was
      detected, as well as gross metallosis around the articulation of the total disc
      prosthesis. A safe and straightforward technique for the extraction of a Maverick
      prosthesis using a hooked instrument to hook-on the keel of the device is
      reported. After removal of the device, an anterior lumbar interbody fusion with
      subsequent posterior pedicle screw fixation and posterior bone grafting with
      autologous iliac bone was performed (360 degrees fusion). During this posterior
      procedure, severe L5S1 facet joint arthrosis was observed. Early clinical and
      radiographic results were good with excellent patient satisfaction.

PMID- 17441670
TI  - Posterior knee dislocation after total knee arthroplasty in a patient with
      multiple sclerosis. A case report.
AB  - A patient with multiple sclerosis (MS) and severe osteoarthritis of the right
      knee with valgus deformity developed early in the postoperative period a
      posterior dislocation of the knee after total knee arthroplasty (TKA), due to
      severe spasm of her hamstring muscles. At revision surgery the posterior cruciate
      retaining prosthesis was exchanged for a non-linked constrained knee prosthesis.
      Technical considerations are described for this rare complication, which remains
      a serious clinical challenge for the orthopaedic surgeon.

PMID- 17441672
TI  - Pyogenic spondylitis as a complication of ear piercing: differentiating between
      spondylitis and discitis.
AB  - We report what is, to our best knowledge, the first case of pyogenic spondylitis
      following ear piercing, a common and popular cosmetic procedure. The spondylitis
      was adequately treated with antibiotics and brace. The value of additional
      diagnostic measures in differentiating between spondylitis and discitis is
      discussed.

PMID- 17441673
TI  - Solitary osteochondroma of the cervical spine causing spinal cord compression.
AB  - Osteochondromas are common benign tumours of bone that often occur in the
      metaphysodiaphyseal parts of long bones. They rarely occur in the spine. We
      present a case of solitary osteochondroma arising from the C-1 vertebral lamina,
      causing neurological symptoms. A 46-year-old man presented to our institution,
      complaining of pain and numbness originating from his neck and extending down to
      his left arm. Radiographs, CT and MRI showed a solitary benign appearing
      expansile bone tumour arising from the left vertebral lamina of C-1, spreading to
      C-2, exerting an eccentric posterolateral compression on the spinal cord in the
      left part of the spinal canal and causing stenosis of the left neural foramen
      between C-1 and C-2. The lesion was surgically explored through a posterior
      longitudinal incision. Leaving the left lateral mass of C-1 intact, a left
      hemilaminectomy was performed. The lesion and the part spreading to C-2 were
      excised, completely clearing the spinal cord compression. For posterior
      stabilisation, lateral mass screws were inserted bilaterally in C-1 and pedicle
      screws and a rod system were used in C-2. The interlaminar region between C-1 and
      C-2 was fused using cancellous allograft chips. Follow-up controls with
      radiological examination revealed that the decompression had been adequate and
      fusion was achieved. Excision of the lesions is necessary to relieve neurological
      compression in such cases. In order to avoid complications associated with
      instability following extensive laminectomy, posterior stabilisation and fusion
      should also be performed.

PMID- 17441674
TI  - Fatal fat embolism following an isolated vertebral fracture.
AB  - The authors report an unusual case of a fat embolism following an isolated lumbar
      vertebra wedge fracture. A 66-year-old gentleman sustained a lumbar wedge
      fracture following a fall. During routine mobilisation some days later he
      collapsed suddenly and became unresponsive. Shortly after, he suffered a fatal
      cardiac arrest. A post-mortem was performed which attributed the cause of death
      to fat embolism. Most previously reported cases of fat embolism are associated
      with long bone fractures and major bony surgery. No apparent case of fatal fat
      embolism following an isolated vertebral fracture has previously been described.

PMID- 17441675
TI  - Re: Detection of adolescent idiopathic scoliosis Fazal & Edgar. Vol. 72 (2): 184
      6.2006.

PMID- 17441677
TI  - Preparation of antibodies for the designer steroid tetrahydrogestrinone and
      development of an enzyme-linked immunosorbent assay for human urine analysis.
AB  - A highly sensitive enzyme-linked immunosorbent assay (ELISA) has been developed
      for tetrahydrogestrinone (THG), the new designer anabolic steroid responsible for
      the well-known Balco scandal announced in year 2003. Antibodies have been raised
      against 18a-homo-pregna-4,9,11-trien-17beta-ol-3-carboxymethyl oxime coupled to
      horseshoe crab hemocyanin. The hapten has been synthesized from gestrinone by
      controlled reduction of the triple bond of the ethinyl group at position C-17,
      without affecting the double bonds of the steroidal rings, followed by reaction
      of the keto group at C-3 with (carboxymethoxy)amine hemihydrochloride to form the
      oxime bond. The antisera obtained has been used in combination with 18a-homo
      pregna-4,9,11-trien-17beta-ol-20-yn-3-carboxymethyl oxime, a hapten derivative of
      gestrinone, coupled to bovine serum albumin to establish a competitive ELISA.
      Under the conditions used, THG can be detected in buffer with a limit of
      detection (LOD) of 0.045 +/- 0.015 microg L(-1) (N = 9). The assay is very
      selective since other steroids assessed are not recognized. Preliminary
      experiments performed with human urine samples demonstrate that the assay can be
      applied to the analysis of these samples after a simple sample treatment method
      reaching a LOD of 0.25 +/- 0.14 microg L(-1). Accuracy is very good as
      demonstrated by the excellent correlation obtained when analyzing blind spiked
      urine samples (slope 0.93, R2 = 0.992).

PMID- 17441676
TI  - T cell immunomonitoring and tumor responses in patients immunized with a complex
      of cholesterol-bearing hydrophobized pullulan (CHP) and NY-ESO-1 protein.
AB  - We recently showed that vaccination with a complex of cholesterol-bearing
      hydrophobized pullulan and NY-ESO-1 protein (CHP-NY-ESO-1) elicited antibody
      responses in 9 of 9 patients vaccinated in a clinical trial. In this study, we
      performed T cell immunomonitoring and analyzed tumor responses in these patients.
      To evaluate CD4 and CD8 T cell responses, an IFN-gamma secretion assay was used.
      The assay showed low background and was sensitive for detecting antigen-specific
      T cells. An increase in the CD4 T cell response was observed in 2 of 2 initially
      sero-positive and 5 of 7 initially sero-negative patients after vaccination. An
      increase in the CD8 T cell response was also observed in 2 of 2 sero-positive and
      5 of 7 sero-negative patients after vaccination. Analysis of peptides recognized
      by CD4 and CD8 T cells revealed two dominant NY-ESO-1 regions, 73-114 and 121
      144. Tumor responses were observed in 3 esophageal cancer patients and a
      malignant melanoma patient. In 3 of 4 prostate cancer patients, prostate-specific
      antigen (PSA) values stabilized during the course of vaccination. The use of
      whole protein, containing multiple CD4 and CD8 epitopes, may be beneficial for
      cancer vaccines to prevent tumors from evading the immune response.

PMID- 17441678
TI  - Probing intrinsic and extrinsic components in single osteosarcoma cells by near
      infrared surface-enhanced Raman scattering.
AB  - We report on the capabilities of near-infrared surface-enhanced Raman scattering
      (SERS) using gold nanoparticles to obtain detailed chemical information with high
      spatial resolution from within single cancer cells, living or fixed. Colloidal
      gold particles, 60 nm in size, were introduced into live human osteosarcoma cells
      by endocytosis by adding them to the growth medium. Rapid SERS mapping of cells
      indicated that not only could rich vibrational spectra be obtained from intrinsic
      cellular constituents both in the cytoplasm and nucleus and but also the
      distribution of extrinsic molecules introduced into the cells, in this case,
      rhodamine 6G could be characterized, suggesting that the intracellular
      distribution of chemotherapeutic agents could potentially be measured by this
      technique. We show that the SERS signal intensity from the cellular components
      increases and more spectral detail is acquired from dried cells when compared
      with hydrated cells in buffer. The data also show spectral fluctuations, mainly
      in intensity but also in peak position, which are dependent upon the intensity of
      the excitation light and are probably due to diffusion of molecules on the
      surface of the gold nanoparticles. A detailed understanding of the origins of
      these effects is still not complete, but the ability to acquire very sensitive
      SERS inside living cancer cells indicates the potential of this technique as a
      useful tool in biomedicine.

PMID- 17441679
TI  - Langmuir-Blodgett patterning: a bottom-up way to build mesostructures over large
      areas.
AB  - This Account describes a new paradigm, Langmuir-Blodgett (LB) patterning, for
      large-area patterning with mesostructured features based on the well-established
      LB technique. This strategy uses a simple fabrication technique to control the
      alignment, size, shape, and periodicity of self-organized phospholipid monolayer
      patterns with feature sizes down to 100 nm over surface areas of square
      centimeters. Because of the anisotropic wetting behavior of the patterns, they
      can be used as templates to direct the self-assembly of functional molecules and
      nanocrystals. Furthermore, the chemical patterns can be converted into
      topographical structures, which can be used to direct cell growth and organize
      nanocrystals. The mesoscopic structured surfaces described here may serve as a
      platform in engineering the biological/material interface and constructing
      biofunctionalized structures and "programmed" systems.

PMID- 17441680
TI  - Molecular interactions in amphiphilic assemblies: theoretical perspective.
AB  - In recent experimental studies, a number of morphological features have been
      revealed on amphiphilic assemblies that need consideration of the molecular
      chiral structure and the molecular polarity. Molecular chirality and polarity
      influence the intermolecular energy profile as a function of the distance and
      orientation between neighboring molecules in the condensed-phase aggregates of
      mono- and bilayers. After the experimental information is summarized, related
      microscopic theoretical works are presented. The molecular theory shows that the
      mesoscopic chiral shape of the condensed phase can be predicted from the
      molecular chiral structure studying the intermolecular energy profile. The
      theoretical insights have implications for related biological systems.

PMID- 17441681
TI  - Sol-gel methods for the assembly of metal chalcogenide quantum dots.
AB  - Sol-gel chemistry represents a powerful method for assembling metal chalcogenide
      quantum dots into 3D connected architectures without the presence of intervening
      ligands to moderate particle-particle interactions. Wet gels prepared by the
      oxidative loss of thiolate surface groups from chalcogenide nanoparticles can be
      converted to xerogels (low porosity) or aerogels (high porosity), and the quantum
      confinement effects in these low-dimensional networks decrease with increasing
      density of the network. In this Account, we describe the application of sol-gel
      chemistry to the formation of CdSe architectures and discuss how surface
      modification can lead to highly luminous monoliths, concluding with the prospects
      of these unique materials for applications in sensing and photovoltaics.

PMID- 17441682
TI  - Synthesis and biological assay of GSH functionalized fluorescent quantum dots for
      staining Hydra vulgaris.
AB  - Quantum dots (QDs) have been used extensively as fluorescent markers in several
      studies on living cells. Here, we report the synthesis of conjugates based on
      glutathione (GSH) and QDs (GSH-QDs) and we prove how these functionalized
      fluorescent probes can be used for staining a freshwater invertebrate called
      Hydra vulgaris. GSH is known to promote Hydra feeding response by inducing mouth
      opening. We demonstrate that GSH-QDs as well are able to elicit biological
      activity in such an animal, which results in the fluorescent staining of Hydra.
      GSH-QDs, once they reach the gastric region, are internalized by endodermal
      cells. The efficiency of GSH-QD internalization increases significantly when
      nanoparticles are coadministrated with free GSH. We also compared the behavior of
      bare QDs to that of GSH-QDs both in the presence and in the absence of free GSH.
      The conclusions from these series of experiments point to the presence of GSH
      binding proteins in the endodermal cell layer and uncover a novel role played by
      glutathione in this organism.

PMID- 17441683
TI  - Chiral O-(Z-alpha-aminoacyl) sugars: convenient building blocks for glycopeptide
      libraries.
AB  - 1,2:3,4-Di-O-isopropylidene-alpha-D-galactopyranose (2), 1,2:5,6-di-O
      isopropylidene-d-glucose (5), and 2,3:5,6-di-O-isopropylidene-alpha-D
      mannofuranose (7) are efficiently O-acylated in 78-96% yields with readily
      available N-(Z-alpha-aminoacyl)benzotriazoles 1a-e, 1d+1d' under microwave
      irradiation to give chiral 3a-d, 4, 6a-d, 8a,b and diastereomeric mixtures
      (3d+3d'), (6a+6a'), and (6d+6d'). The original chirality was retained as
      evidenced by HPLC. The diisopropylidene protecting groups were removed from
      compounds 3a,d, 6d to give the free O-(Z-alpha-aminoacyl) sugars 9a,b, 10.

PMID- 17441684
TI  - Adsorption mechanisms in normal-phase chromatography. Mobile-phase modifier
      adsorption from dilute solutions and displacement effect.
AB  - The adsorption equilibria of methanol from diluted solutions of the alcohol in
      dichloromethane (the weak solvent of the binary mixture) have been investigated
      in normal-phase conditions on an hybrid polymeric chiral stationary phase. This
      was done by analyzing the shapes of nonlinear perturbations of methanol, measured
      with a refractive index detector from a column in equilibrium with pure
      dichloromethane. Experiments have been set up to demonstrate the displacement
      effect, predictable from the adsorption data, by a nonlinear pulse of methanol on
      a racemic mixture of temazepam injected at trace level. A most used method in
      fundamental studies of band behavior in chromatography has been used for modeling
      the system. An extraordinary increase of the apparent column efficiency has been
      observed due to the displacement phenomenon, with the peak of the second eluted
      enantiomer noticeably higher and narrower than that of the first eluted
      component.

PMID- 17441685
TI  - Direct evidence of arsenic(III)-carbonate complexes obtained using
      electrochemical scanning tunneling microscopy.
AB  - Electrochemical scanning tunneling microscopy (ECSTM), ion chromatography (IC),
      and electrospray ionization-mass spectrometry/mass spectrometry were applied to
      investigate the interactions between arsenite [As(III)] and carbonate and
      arsenate [As(V)] and carbonate. The chemical species in the single and binary
      component solutions of As(III), As(V), and carbonate were attached to a Au(111)
      surface and then imaged in a 0.1 M NaClO4 solution at the molecular level by
      ECSTM. The molecules formed highly ordered adlayers on the Au(111) surface. High
      resolution STM images revealed the orientation and packing arrangement of the
      molecular adlayers. Matching the STM images with the molecular models constructed
      using the Hyperchem software package indicated that As(III) formed two types of
      complexes with carbonate, including As(OH)2CO3- and As(OH)3(HCO3-)2. No complexes
      were formed between As(V) and carbonate. IC chromatograms of the solutions
      revealed the emergence of the new peak only in the aged As(III)-carbonate
      solution. MS spectra showed the presence of a new peak at m/z 187 in the aged
      As(III)-carbonate solution. The results obtained with the three independent
      methods confirmed the formation of As(OH)2CO3-. The results also indicated that
      As(OH)3 could be associated with HCO3- through a hydrogen bond. The knowledge of
      the formation of the As(III) and carbonate complexes will improve the
      understanding of As(III) mobility in the environment and removal of As(III) in
      water treatment systems.

PMID- 17441686
TI  - Analytical significance of encroachment in multiplexed bead-based flow cytometric
      assays.
AB  - Multiplexed bead-based assays, using fluorescent dye-encoded beads, are finding
      widespread use in various profiling studies. The need to measure multiple
      quantitative responses simultaneously, the development of less expensive
      commercial flow systems, and the ease and cost effectiveness of manufacturing
      bead profiling kits of varied composition have all contributed to the popularity
      of this assay format. Maximizing the level of multiplexing in these assays
      requires tight spacing of fluorescent bead populations, and this leads to some
      degree of overlap or "encroachment" between populations. The degree to which
      encroachment affects analyte signal determinations depends upon both the extent
      of overlap and the relative analyte signals associated with the populations. In
      the work reported here, the impact of encroachment upon analyte signal for a
      subset of beads belonging to a multiplexed cytokine assay has been modeled and
      empirically evaluated.

PMID- 17441687
TI  - Supercritical fluid chromatography and high-performance liquid
      chromatography/tandem mass spectrometric methods for the determination of
      cytarabine in mouse plasma.
AB  - The separation of cytarabine (ara-C) from the endogenous compounds in mouse
      plasma by packed-column supercritical fluid chromatography (pSFC) was achieved on
      bare silica stationary phase with an isocratic mobile phase composed of
      CO2/methanol solvent with addition of ammonium acetate. SFC is commonly assumed
      to be only applicable to nonpolar and relatively low-polarity compounds. In this
      work, a broader range of compound polarities amenable to pSFC with appropriate
      mobile-phase modifiers and additives under normal-phase retention mechanism was
      demonstrated. The pSFC was integrated with an atmospheric pressure chemical
      ionization source and a tandem mass spectrometer (MS/MS) to enhance the
      sensitivity, selectivity, and speed of the assay. The influence of mobile-phase
      components on chromatographic performance and ionization efficiency of the test
      compounds was investigated for improving the sensitivity and separation for the
      analyte and the internal standard. The pSFC-MS/MS approach requiring
      approximately 2.5 min/sample for the determination of ara-C at nanograms per
      milliliter in mouse plasma was partially validated with respect to stability,
      linearity, and reproducibility. The mouse plasma levels of ara-C obtained by the
      pSFC-MS/MS method were found to be consistent with those determined by various
      reversed-phase, high-performance liquid chromatography methods using a porous
      graphite carbon column, a mixed-mode column, or a C18 column in conjunction with
      an ion-pairing agent coupled to a tandem mass spectrometer.

PMID- 17441689
TI  - Probability model for assessing proteins assembled from peptide sequences
      inferred from tandem mass spectrometry data.
AB  - In shotgun proteomics, tandem mass spectrometry is used to identify peptides
      derived from proteins. After the peptides are detected, proteins are reassembled
      via a reference database of protein or gene information. Redundancy and homology
      between protein records in databases make it challenging to assign peptides to
      proteins that may or may not be in an experimental sample. Here, a probability
      model is introduced for determining the likelihood that peptides are correctly
      assigned to proteins. This model derives consistent probability estimates for
      assembled proteins. The probability scores make it easier to confidently identify
      proteins in complex samples and to accurately estimate false-positive rates. The
      algorithm based on this model is robust in creating protein complements from
      peptides from bovine protein standards, yeast, Ustilago maydis cell lysates, and
      Arabidopsis thaliana leaves. It also eliminates the side effects of redundancy
      and homology from the reference databases by employing a new concept of peptide
      grouping and by coherently distinguishing distinct peptides from unique records
      and shared peptides from homologous proteins. The software that runs the
      algorithm, called PANORAMICS, provides a tool to help analyze the data based on a
      researcher's knowledge about the sample. The software operates efficiently and
      quickly compared to other software platforms.

PMID- 17441688
TI  - Implementation of electron-transfer dissociation on a hybrid linear ion trap
      orbitrap mass spectrometer.
AB  - We describe the adaptation of a hybrid quadrupole linear ion trap-orbitrap mass
      spectrometer to accommodate electron-transfer ion/ion reactions (ETD) for peptide
      and protein characterization. The method utilizes pulsed, dual electrospray ion
      sources and requires minimal instrument modification. Switching between cation
      and reagent anion injection schemes is automated and accomplished within a few
      hundred milliseconds. Ion/ion reactions are conducted within the linear ion trap,
      after which the c- and z-type product ions are passed to the orbitrap for high
      resolution m/z analysis. With this arrangement, mass accuracies are typically
      measured to within 2 ppm at a resolving power of approximately 60 000. Using
      large peptides and intact proteins, we demonstrate such capabilities will
      accelerate our ability to interrogate high-mass species. To illustrate
      compatibility with automated data-dependent analysis and subsequent data
      processing, we couple the technique with an online chromatographic separation of
      a yeast whole-cell lysate followed by peptide identification using ProSight PC.
      Fairly long pulsing times and relatively low ET efficiency, as compared to
      conventional ETD instrumentation, are the main drawbacks of this approach. Still,
      our results suggest that the implementation of ETD on sensitive, high-resolution,
      and high-mass accuracy hybrid instrumentation, such as the orbitrap, will
      substantially propel the emergent fields of middle- and top-down proteomics.

PMID- 17441690
TI  - Quantitative analysis of adsorbate concentrations by diffuse reflectance FT-IR.
AB  - Fully quantitative analyses of DRIFTS data are required when the surface
      concentrations and the specific rate constants of reaction (or desorption) of
      adsorbates are needed to validate microkinetic models. The relationship between
      the surface coverage of adsorbates and various functions derived from the signal
      collected by DRIFTS is discussed here. The Kubelka-Munk and pseudoabsorbance
      (noted here as absorbance, for the sake of brevity) transformations were
      considered, since those are the most commonly used functions when data collected
      by DRIFTS are reported. Theoretical calculations and experimental evidence based
      on the study of CO adsorption on Pt/SiO2 and formate species adsorbed on Pt/CeO2
      showed that the absorbance (i.e., = log 1/R', with R' = relative reflectance) is
      the most appropriate, yet imperfect, function to give a linear representation of
      the adsorbate surface concentration in the examples treated here, for which the
      relative reflectance R' is typically > 60%. When the adsorbates lead to a strong
      signal absorption (e.g., R' < 60%), the Kubelka-Munk function is actually more
      appropriate. The absorbance allows a simple correction of baseline drifts, which
      often occur during time-resolved data collection over catalytic materials.
      Baseline corrections are markedly more complex in the case of the other
      mathematical transforms, including the function proposed by Matyshak and Krylov
      (Catal. Today 1995, 25, 1-87), which has been proposed as an appropriate
      representation of surface concentrations in DRIFTS spectroscopy.

PMID- 17441691
TI  - Structure and function of transmembrane segment XII in osmosensor and
      osmoprotectant transporter ProP of Escherichia coli.
AB  - Escherichia coli transporter ProP acts as both an osmosensor and an
      osmoregulator. As medium osmolality rises, ProP is activated and mediates H+
      coupled uptake of osmolytes like proline. A homology model of ProP with 12
      transmembrane (TM) helices and cytoplasmic termini was created, and the protein's
      topology was substantiated experimentally. Residues 468-497, at the end of the C
      terminal domain and linked to TM XII, form an intermolecular, homodimeric alpha
      helical coiled-coil that tunes the transporter's response to osmolality. We aim
      to further define the structure and function of ProP residues Q415-E440,
      predicted to include TM XII. Each residue was replaced with cysteine (Cys) in a
      histidine-tagged, Cys-less ProP variant (ProP*). Cys at positions 415-418 and 438
      440 were most reactive with Oregon Green Maleimide (OGM), suggesting that
      residues 419 through 437 are in the membrane. Except for V429-I433, reactivity of
      those Cys varied with helical periodicity. Cys predicted to face the interior of
      ProP were more reactive than Cys predicted to face the lipid. The former may be
      exposed to hydrated polar residues in the protein interior, particularly on the
      periplasmic side. Intermolecular cross-links formed when ProP* variants with Cys
      at positions 419, 420, 422, and 439 were treated with DTME. Thus TM XII can
      participate, along its entire length, in the dimer interface of ProP. Cys
      substitution E440C rendered ProP* inactive. All other variants retained more than
      30% of the proline uptake activity of ProP* at high osmolality. Most variants
      with Cys substitutions in the periplasmic half of TM XII activated at lower
      osmolalities than ProP*. Variants with Cys substitutions on one face of the
      cytoplasmic half of TM XII required a higher osmolality to activate. They
      included elements of a GXXXG motif that are predicted to form the interface of TM
      XII with TM VII. These studies define the position of ProP TM XII within the
      membrane, further support the predicted structure of ProP, reveal the
      dimerization interface, and show that the structure of TM XII influences the
      osmolality at which ProP activates.

PMID- 17441692
TI  - Mutagenesis of p38alpha MAP kinase establishes key roles of Phe169 in function
      and structural dynamics and reveals a novel DFG-OUT state.
AB  - In order to study the role of Phe169 in p38alpha MAP kinase structure and
      function, wild-type p38alpha and five p38alpha DFG motif mutants were examined in
      vitro for phosphorylation by MKK6, kinase activity toward ATF2 substrate, thermal
      stability, and X-ray crystal structure. All six p38alpha variants were
      efficiently phosphorylated by MKK6. However, only one activated p38alpha mutant
      (F169Y) possessed measurable kinase activity (1% compared to wild-type). The loss
      of kinase activity among the DFG mutants may result from an inability to
      correctly position Asp168 in the activated form of p38alpha. Two mutations
      significantly increased the thermal stability of p38alpha (F169A DeltaTm = 1.3
      degrees C and D168G DeltaTm = 3.8 degrees C), and two mutations significantly
      decreased the stability of p38alpha (F169R DeltaTm = -3.2 degrees C and F169G
      DeltaTm = -4.7 degrees C). Interestingly, X-ray crystal structures of two
      thermally destabilized p38alpha-F169R and p38alpha-F169G mutants revealed a DFG
      OUT conformation in the absence of an inhibitor molecule. This DFG-OUT
      conformation, termed alpha-DFG-OUT, is different from the ones previously
      identified in p38alpha crystal structures with bound inhibitors and postulated
      from high-temperature molecular dynamics simulations. Taken together, these
      results indicate that Phe169 is optimized for p38alpha functional activity and
      structural dynamics, rather than for structural stability. The alpha-DFG-OUT
      conformation observed for p38alpha-F169R and p38alpha-F169G may represent a
      naturally occurring intermediate state of p38alpha that provides access for
      binding of allosteric inhibitors. A model of the local forces driving the DFG IN
      OUT transition in p38alpha is proposed.

PMID- 17441693
TI  - First-principles thermochemistry for the production of TiO2 from TiCl4.
AB  - Despite the industrial importance of the process, the detailed chemistry of the
      high-temperature oxidation of titanium tetrachloride (TiCl4) to produce titania
      (TiO2) nanoparticles remains unknown, partly due to a lack of thermochemical
      data. This work presents the thermochemistry of many of the intermediates in the
      early stages of the mechanism, computed using quantum chemistry. The enthalpies
      of formation and thermochemical data for TiOCl, TiOCl2, TiOCl3, TiO2Cl2, TiO2Cl3,
      Ti2O2Cl3, Ti2O2Cl4, Ti2O3Cl2, Ti2O3Cl3, Ti3O4Cl4, and Ti5O6Cl8 were calculated
      using density functional theory (DFT). The use of isodesmic and isogyric
      reactions was shown to be important for determining standard enthlapy of
      formation (Delta(f)H(degree)(298K)) values for these transition metal oxychloride
      species. TiOCl2, of particular importance in this mechanism, was also studied
      with CCSD(T) and found to have Delta(f)H(degree)(298K) = -598 +/- 20 kJ/mol.
      Finally, equilibrium calculations were performed to identify which intermediates
      are likely to be most prevalent in the high temperature industrial process, and
      as a first attempt to identify the size of the critical nucleus.

PMID- 17441694
TI  - Electronic structure and bonding of {Fe(PhNO2)}6 complexes: a density functional
      theory study.
AB  - Reduction of nitro-aromatic compounds (NACs) proceeds through intermediates with
      a partial electron transfer into the nitro group from a reducing agent. To
      estimate the extent of such a transfer and, therefore, the activity of various
      model ferrous-containing reductants toward NAC degradation, the unrestricted
      density functional theory (DFT) in the basis of paired Lowdin-Amos-Hall orbitals
      has been applied to complexes of nitrobenzene (NB) and model Fe(II) hydroxides
      including cationic [FeOH]+, then neutral Fe(OH)2, and finally anionic [Fe(OH)3]-.
      Electron transfer is considered to be a process of unpairing electrons (without
      the change of total spin projection Sz) that reveals itself in a substantial spin
      contamination of the unrestricted solution. The unrestricted orbitals are
      transformed into localized paired orbitals to determine the orbital channels for
      a particular electron-transfer state and the weights of idealized charge-transfer
      and covalent electron structures. This approach allows insight into the
      electronic structure and bonding of the {Fe(PhNO2)}6 unit (according to Enemark
      and Feltham notation) to be gained using model nitrobenzene complexes. The
      electronic structure of this unit can be expressed in terms of pi-type covalent
      bonding [Fe+2(d6, S = 2) - PhNO2(S = 0)] or charge-transfer configuration
      [Fe+3(d5, S = 5/2) - {PhNO2}- ((pi*)1, S = 1/2)].

PMID- 17441695
TI  - Ab initio study of the ClO + NH2 reaction: prediction of the total rate constant
      and product branching ratios.
AB  - The mechanism for ClO + NH2 has been investigated by ab initio molecular orbital
      and transition-state theory calculations. The species involved have been
      optimized at the B3LYP/6-311+G(3df,2p) level and their energies have been refined
      by single-point calculations with the modified Gaussian-2 method, G2M(CC2). Ten
      stable isomers have been located and a detailed potential energy diagram is
      provided. The rate constants and branching ratios for the low-lying energy
      channel products including HCl + HNO, Cl + NH2O, and HOCl + 3NH (X(3)Sigma(-))
      are calculated. The result shows that formation of HCl + HNO is dominant below
      1000 K; over 1000 K, Cl + NH2O products become dominant. However, the formation
      of HOCl + 3NH (X(3)Sigma(-)) is unimportant below 1500 K. The pressure
      independent individual and total rate constants can be expressed as k1(HCl + HNO)
      = 4.7 x 10(-8)(T(-1.08)) exp(-129/T), k(2)(Cl + NH2O) = 1.7 x 10(-9)(T(-0.62))
      exp(-24/T), k3(HOCl + NH) = 4.8 x 10(-29)(T5.11) exp(-1035/T), and k(total) = 5.0
      x 10(-9)(T(-0.67)) exp(-1.2/T), respectively, with units of cm(3) molecule(-1) s(
      1), in the temperature range of 200-2500 K.

PMID- 17441696
TI  - Photoinduced dynamics of hydrated adenine clusters.
AB  - We studied the photoinduced dynamics of hydrated adenine clusters by multiphoton
      ionization techniques. The majority of the hydrated adenine monomers are found to
      experience dissociative ionization, where the adenine monomer ions are produced
      due to the fragmentation of the water solvents by three-photon process. Due to
      fast internal conversion from the electronic states reached by the first photon,
      the fragmentation takes place in the vibrationally excited electronic ground
      state and in the vibrationally excited ionic states. Thus, the abundance of the
      hydrated adenine monomer ion depends on the excitation photon energy, possibly
      because the lifetime of the intermediate states is different and an internal
      conversion competes with direct ionization. In addition, a significant amount of
      protonated adenine monomer is observed. This indicates that the proton transfer
      is followed by the fragmentation in the hydrated adenine clusters. The abundance
      of the protonated adenine monomer also depends on the excitation photon energy
      mainly due to the ionization efficiency of the parent species.

PMID- 17441697
TI  - Ab initio analysis of the structural properties of alkyl-substituted polyhedral
      oligomeric silsesquioxanes.
AB  - Ab initio quantum mechanical calculations have been performed to establish the
      potentials for alkyl-substituted polyhedral oligomeric silsesquioxane (POSS)
      monomers RxH8-x(SiO1.5)8. More specifically, we have examined the unsubstituted
      POSS (SiO1.5H)8 cage as well as linear and cyclic alkyl-substituted cages where
      one of the terminating hydrogen atoms is replaced by a hydrocarbon group, that
      is, R1H7(SiO1.5)8. The results for the minimum-energy configurations indicate
      that the presence of the linear hydrocarbon chains and cyclic intermediates have
      very little effect on the structure of the POSS cage. Although the POSS monomeric
      cage does influence the partial charges of the first few carbon atoms covalently
      bound to the POSS monomer, its effect on the structural properties of the alkyl
      chain is small. Differences arise, however, for cyclic alkyl substitutents bound
      to the POSS cage due to the repulsive interactions between the POSS cage and
      bulkier cyclic intermediates that result upon rotation of the Si-C-C-C dihedral
      angles. The interatomic potentials for these rotational, or torsional, terms need
      to be modified slightly in order to appropriately simulate sterically hindered
      substitutents on the cage. Our results suggest that combining an atomistic force
      field independently developed to describe silsesquioxanes with an independent
      atomistic model developed to describe hydrocarbon chains can be used in classical
      molecular simulation studies of most alkyl-silsesquioxanes. This avoids the need
      to develop specific force fields for each substituted POSS cage studied and opens
      up the possibility of using molecular simulation to probe the thermodynamic and
      structural properties of these unique nanoscale building blocks.

PMID- 17441698
TI  - Correlation effects in EOM-CCSD for the excited states: evaluated by AIM
      localization index (LI) and delocalization index (DI).
AB  - We have extended the evaluation and interpretation of QTAIM (quantum theory of
      atoms in molecules) localization and delocalization indices lambda (LI) and delta
      (DI) to electronic excited states by studying ground states (at HF and CCSD
      levels) and excited states (at CIS and EOM-CCSD) of H2C=CH2, HCCH, H2C=O, H2C=S,
      CO2, CS2, and SO2. These molecules undergo extensive geometrical changes upon the
      excitation to the valence adiabatic excited singlet state. The importance of
      Coulomb correlation effects was demonstrated by comparing the LIs and DIs at none
      correlated levels (HF and CIS) and those at correlated levels (CCSD and EOM
      CCSD). In interpreting the changes in the magnitudes of the LIs and DIs, we made
      use of simple molecular orbital and Walsh-diagram analyses. Coulomb correlation
      is important in determining the magnitude of the LIs and DIs and obtaining
      geometries that are close to experiment.

PMID- 17441699
TI  - Infrared spectroscopy of ozone-water complex in a neon matrix.
AB  - Matrix isolation infrared spectroscopy has been applied to study an ozone-water
      complex of atmospheric interest. The complex was identified in the spectral
      region of three normal modes of ozone and water. Ab initio calculation at
      MP4(SDQ), QCISD, and CCSD(T) levels indicates the existence of only one stable
      conformer, which accords with the present experimental result. This conformer
      belongs to the Cs symmetry group where two molecular planes of ozone and water
      are perpendicular to the Cs symmetry plane. The binding energy was calculated to
      be 1.89 kcal/mol at the CCSD(T)/6-311++G(3df,3pd)//CCSD(T)/6-311++G(d,p) level of
      theory. The formation constant and atmospheric abundance of the ozone-water
      complex are estimated using the thermodynamic and spectroscopic data obtained.

PMID- 17441700
TI  - Possible gas-phase reactions of H2/CH4/tetramethylsilane in diamond/beta-SiC
      nanocomposite film deposition: an ab-initio study.
AB  - The Si-C bond breakings in tetramethylsilane (TMS) when interacting with H/H2 and
      the successive H abstractions from SiH4/CH4 in the gas mixture of H2/ CH4/TMS
      were studied at the CCSD(T)/6-311+G**//MP2/6-31+G** level of theory. Their rate
      constants between 1500 and 2500 K were estimated using a conventional transition
      state theory. The results indicate that (i) it is mainly the H radical that
      causes the Si-C bond breaking in TMS, and (ii) the successive H abstractions from
      SiH4 are much easier and faster than those from CH4. At low temperatures the
      differences of rate constants among the four types of the reactions are large,
      but generally reduced at high temperatures. The reaction rates show no
      selectivity over the pressure as verified at P = 0.00025, 0.025, 1, and 100 atm,
      respectively. Our results could provide the following microscopic level
      understanding of reactions in the synthesis of diamond/beta-SiC nanocomposite
      films. Although the Si content is smaller than that of C in the precursor gases,
      the gas mixture activated by microwave plasma technique could provide Si sources
      with a higher rate. The produced Si sources with excellent rigidity in sp3
      hybridization competitively occupy the space on the substrate together with C
      sources, resulting in the deposition of diamond/beta-SiC nanocomposite films.

PMID- 17441701
TI  - Density functional theory treatment of electron correlation in the nuclear
      electronic orbital approach.
AB  - This paper presents the nuclear-electronic orbital density functional theory [NEO
      DFT(ee)] method for including electron-electron correlation and nuclear quantum
      effects self-consistently in quantum chemical calculations. The NEO approach is
      designed to treat a relatively small number of nuclei quantum mechanically, while
      the remaining nuclei are treated classically. In the NEO-DFT(ee) approach, the
      correlated electron density is used to obtain the nuclear molecular orbitals, and
      the resulting nuclear density is used to obtain the correlated electron density
      during an iterative procedure that continues until convergence of both the
      nuclear and electronic densities. This approach includes feedback between the
      correlated electron density and the nuclear wavefunction. The application of this
      approach to bihalides and acetylene indicates that the nuclear quantum effects do
      not significantly impact the electron correlation energy, but the quantum nuclear
      energy is enhanced in the NEO-DFT(ee) B3LYP method. The excellent agreement of
      the NEO-DFT(ee)-optimized bihalide structures with the vibrationally averaged
      geometries from grid-based quantum dynamical methods provides validation for the
      NEO-DFT(ee) approach. Electron-proton correlation could be included by the
      development of an electron-nucleus correlation functional. Alternatively,
      explicit electron-proton correlation could be included directly into the NEO self
      consistent-field framework with Gaussian-type geminal functions.

PMID- 17441702
TI  - Infrared spectroscopic and density functional theory study on the reactions of
      lanthanum atoms with carbon dioxide in rare-gas matrices.
AB  - Reactions of laser-ablated La atoms with CO2 molecules in solid argon and neon
      have been investigated using matrix-isolation infrared spectroscopy. On the basis
      of isotopic shifts, mixed isotopic splitting patterns, and CCl4-doping
      experiments, absorptions at 1839.9 and 753.6 cm-1 in argon and 1855.9 and 771.3
      cm-1 in neon are assigned to the C-O and La-O stretching vibrations of the OLaCO
      molecule, respectively. Ultraviolet-visible photoinduced isomerization of OLaCO
      to La-(eta2-OC)O and OLa-(eta2-CO) have been observed under different wavelength
      photolyses in the solid matrix. The neon matrix experiments give the C-O and La-O
      stretching vibrations of the OLaCO- anion at 1769.5 and 779.3 cm-1, respectively.
      Density functional theory calculations have been performed on these products,
      which support the experimental assignments of the infrared spectra. The present
      study reveals that the C-O stretching vibrational frequencies of OMCO decrease
      from Sc to La, which indicates an increase in metal d orbital --> CO pi* back
      donation in this series.

PMID- 17441703
TI  - Relationship of potency and resilience to drug resistant mutations for GW420867X
      revealed by crystal structures of inhibitor complexes for wild-type, Leu100Ile,
      Lys101Glu, and Tyr188Cys mutant HIV-1 reverse transcriptases.
AB  - The selection of drug resistant viruses is a major problem in efforts to combat
      HIV and AIDS, hence, new compounds are required. We report crystal structures of
      wild-type and mutant HIV-1 RT with bound non-nucleoside (NNRTI) GW420867X, aimed
      at investigating the basis for its high potency and improved drug resistance
      profile compared to the first-generation drug nevirapine. GW420867X occupies a
      smaller volume than many NNRTIs, yet accesses key regions of the binding pocket.
      GW420867X has few contacts with Tyr188, hence, explaining the small effect of
      mutating this residue on inhibitor-binding potency. In a mutated NNRTI pocket,
      GW420867X either remains in a similar position compared to wild-type
      (RT(Leu100Ile) and RT(Tyr188Cys)) or rearranges within the pocket
      (RT(Lys101Glu)). For RT(Leu100Ile), GW420867X does not shift position, in spite
      of forming different side-chain contacts. The small bulk of GW420867X allows
      adaptation to a mutated NNRTI binding site by repositioning or readjustment of
      side-chain contacts with only small reductions in binding affinity.

PMID- 17441704
TI  - Chemical insights in the concept of hybrid drugs: the antitumor effect of nitric
      oxide-donating aspirin involves a quinone methide but not nitric oxide nor
      aspirin.
AB  - Hybrid drug 1 (NO-ASA) continues to attract intense research from chemists and
      biologists alike. It consists of ASA and a -ONO2 group connected through a spacer
      and is in preclinical development as an antitumor drug. We report that, contrary
      to current beliefs, neither ASA nor NO contributes to this antitumor effect.
      Rather, an unsubstituted QM was identified as the sole cytotoxic agent. QM forms
      from 1 after carboxylic ester hydrolysis and, in accordance with the HSAB theory,
      selectively reacts with cellular GSH, which in turn triggers cell death.
      Remarkably, a derivative lacking ASA and the -ONO2 group is 10 times more
      effective than 1. Thus, our data provide a conclusive molecular mechanism for the
      antitumor activity of 1. Equally importantly, we show for the first time that a
      "presumed invisible" linker in a hybrid drug is not so invisible after all and is
      in fact solely responsible for the biological effect.

PMID- 17441705
TI  - Discovery of alogliptin: a potent, selective, bioavailable, and efficacious
      inhibitor of dipeptidyl peptidase IV.
AB  - Alogliptin is a potent, selective inhibitor of the serine protease dipeptidyl
      peptidase IV (DPP-4). Herein, we describe the structure-based design and
      optimization of alogliptin and related quinazolinone-based DPP-4 inhibitors.
      Following an oral dose, these noncovalent inhibitors provide sustained reduction
      of plasma DPP-4 activity and a lowering of blood glucose in animal models of
      diabetes. Alogliptin is currently undergoing phase III trials in patients with
      type 2 diabetes.

PMID- 17441706
TI  - Synthesis and antimalarial property of orally active phenoxazinium salts.
AB  - Phenoxazinium salts were found to display good antimalarial efficacy in vivo
      against Plasmodium berghei. Several compounds provided 100% parasitemia clearance
      at a dose of 20-30 mg kg-1x4 days (ip) and good survival effects without obvious
      acute toxicity. They also showed excellent potency by oral administration. A
      preliminary pharmacokinetic study revealed that the oral availability of 1a was
      excellent.

PMID- 17441707
TI  - Escherichia coli versus Pseudomonas aeruginosa deacetylase LpxC inhibitors
      selectivity: surface and cavity-depth-based analysis.
AB  - Although Escherichia coli and Pseudomonas aeruginosa LpxC share sequence and
      functional similarity, E. coli LpxC inhibitiors are ineffective against P.
      aeruginosa LpxC. It was earlier speculated that inactivity of the inhibitors is
      due to intrinsic resistance possibly mediated by efflux pumps. However, a recent
      study has documented that the inactivity is due to failure of inhibitor(s) to
      inhibit the enzyme rather then intrinsic resistance. In this study, we carried
      out a surface and cavity-depth-based analysis on homology models of E. coli and
      P. aeruginosa LpxC to get some new insights into the ligand-binding features of
      these enzymes. The surface analysis of the P. aeruginosa LpxC model suggested
      that the LpxC catalytic domain (where inhibitors are supposed to bind) has
      several minor but potentially important structural differences as compared to E.
      coli LpxC. Molecular docking studies which could distinguish between the reported
      receptor affinities of the inhibitors additionally helped in the identification
      of key binding-site residues and interactions. These differences can be exploited
      for designing broad-spectrum LpxC inhibitors against this target.

PMID- 17441708
TI  - Structure and bonding in SnWO4, PbWO4, and BiVO4: lone pairs vs inert pairs.
AB  - Three ternary oxides, SnWO4, PbWO4, and BiVO4, containing p-block cations with
      ns2np0 electron configurations, so-called lone pair cations, have been studied
      theoretically using density functional theory and UV-visible diffuse reflectance
      spectroscopy. The computations reveal significant differences in the underlying
      electronic structures that are responsible for the varied crystal chemistry of
      the lone pair cations. The filled 5s orbitals of the Sn2+ ion interact strongly
      with the 2p orbitals of oxygen, which leads to a significant destabilization of
      symmetric structures (scheelite and zircon) favored by electrostatic forces. The
      destabilizing effect of this interaction can be significantly reduced by lowering
      the symmetry of the Sn2+ site to enable the antibonding Sn 5s-O 2p states to mix
      with the unfilled Sn 5p orbitals. This interaction produces a localized,
      nonbonding state at the top of the valence band that corresponds closely with the
      classical notion of a stereoactive electron lone pair. In compounds containing
      Pb2+ and Bi3+ the relativistic contraction of the 6s orbital reduces its
      interaction with oxygen, effectively diminishing its role in shaping the crystal
      chemical preferences of these ions. In PbWO4 this leads to a stabilization of the
      symmetric scheelite structure. In the case of BiVO4 the energy of the Bi 6s
      orbital is further stabilized. Despite this stabilization, the driving force for
      a stereoactive lone pair distortion appears to be enhanced. The energies of
      structures exhibiting distorted Bi3+ environments are competitive with structures
      that possess symmetric Bi3+ environments. Nevertheless, the "lone pair" that
      results associated with a distorted Bi3+ environment in BiVO4 is more diffuse
      than the Sn2+ lone pair in beta-SnWO4. Furthermore, the distortion has a much
      smaller impact on the electronic structure near the Fermi level.

PMID- 17441709
TI  - Kinetics and mechanism of the photoinitiated autoxidation of sulfur(IV) in the
      presence of iodide ion.
AB  - The kinetics and mechanism of the photoinitiated and iodide ion-catalyzed aqueous
      autoxidation of sulfur(IV) has been studied in a diode-array spectrophotometer
      using the same light beam for excitation and detection. Light absorption of both
      the iodide ion and sulfur(IV) contribute to the initiation of a highly efficient
      radical chain reaction, the overall rate of which depends on the reactant and
      catalyst concentrations, the pH, and the light intensity in a complex manner. To
      interpret all the experimental findings, an elaborate scheme is proposed, in
      which the chain carriers are SO3-*, SO4-*, SO5-*, I*, and I2-*. There are three
      termination steps, each of them is second-order with respect to the chain
      carriers. Model calculations and nonlinear fitting have been used to show that
      the proposed scheme gives an excellent quantitative interpretation of the
      experimental results.

PMID- 17441710
TI  - Mn(II) and Cu(II) complexes of a dithiadiazolyl radical ligand: monomer/dimer
      equilibria in solution.
AB  - Complexes of the 4-(2'-pyridyl)-1,2,3,5-dithiadiazolyl radical bidentate ligand
      with bis(hexafluoroacetylacetonato)manganese(II) and with
      bis(hexafluoroacetylacetonato)copper(II) have been prepared. Unlike the
      previously reported cobalt(II) complex, these complexes form dimers via
      intermolecular S...S contacts in the solid state. The spectroscopic and magnetic
      properties of these species in the solid state and in solution are reported and
      compared to the previously reported Co(II) complex, with emphasis on the
      elucidation of the a monomer/dimer equilibrium in the solution. The
      electrochemical properties of these species in solution are also presented and
      discussed.

PMID- 17441711
TI  - Hexaazamacrocyclic nickel and copper complexes and their reactivity with
      tetracyanoquinodimethane.
AB  - The hexaazamacrocycle 1,4,7,10,13,16-hexaazacyclooctadecane, [18]ane-N6, forms
      mono- and dinuclear derivatives with copper chloride depending on the reaction
      stoichiometries and times. The mononuclear derivative, [Cu([18]ane-N6)]Cl2.H2O,
      presents the macrocycle wrapped around the metal atom in a distorted octahedral
      coordinative environment, while the dinuclear derivative, [Cu2([18]ane
      N6)Cl2]Cl2.4H2O, is formed by a central Cu2Cl2 core surrounded by an almost
      planar macrocycle. The crystal structure of both derivatives is stabilized by a
      network of hydrogen bonds involving the amine macrocyclic groups, the chloride
      anions, and the crystallization water molecules. The copper atoms in the
      dinuclear derivative show a strong antiferromagnetic coupling, as expected for
      the crystal structure parameters. A mononuclear nickel derivative has also been
      obtained from nickel nitrate by following the same synthetic procedure. These
      compounds react with TCNQ salts with formation of two types of derivatives,
      [M([18]ane-N6)](TCNQ)2 and [M([18]ane-N6)](TCNQ)4, depending on the use of
      radical-anionic or mixed-valence TCNQ salts in the reaction. The crystal
      structures of the nickel derivatives show that the former derivatives are built
      up by macrocyclic metal cations surrounded by dimeric dianions (TCNQ)22-, either
      isolated or stacked along the crystal. The derivative with four TCNQ
      units/formula consists of alternated chains of metallomacrocyclic cations and
      stacked TCNQ anions. The crystal parameters suggest that every TCNQ holds
      approximately 0.5 electrons and overlaps with a neighboring unit to form dimeric
      monoanions, (TCNQ)2-.

PMID- 17441712
TI  - Chloro half-sandwich osmium(II) complexes: influence of chelated N,N-ligands on
      hydrolysis, guanine binding, and cytotoxicity.
AB  - Relatively little is known about the kinetics or the pharmacological potential of
      organometallic complexes of osmium compared to its lighter congeners, iron and
      ruthenium. We report the synthesis of seven new complexes, [(eta6
      arene)Os(NN)Cl]+, containing different bidentate nitrogen (N,N) chelators, and a
      dichlorido complex, [(eta6-arene)Os(N)Cl2]. The X-ray crystal structures of seven
      complexes are reported: [(eta6-bip)Os(en)Cl]PF6 (1PF6), [(eta6-THA)Os(en)Cl]BF4
      (2BF4), [(eta6-p-cym)Os(phen)Cl]PF6 (5PF6), [(eta6-bip)Os(dppz)Cl]PF6 (6PF6),
      [(eta6-bip)Os(azpy-NMe2)Cl]PF6 (7PF6), [(eta6-p-cym)Os(azpy-NMe2)Cl]PF6 (8PF6),
      and [(eta6-bip)Os(NCCH3-N)Cl2] (9), where THA = tetrahydroanthracene, en =
      ethylenediamine, p-cym = p-cymene, phen = phenanthroline, bip = biphenyl, dppz =
      [3,2-a: 2',3'-c]phenazine and azpy-NMe2 = 4-(2-pyridylazo)-N,N-dimethylaniline.
      The chelating ligand was found to play a crucial role in enhancing aqueous
      stability. The rates of hydrolysis at acidic pH* decreased when the primary amine
      N-donors (NN = en, t1/2 = 0.6 h at 318 K) are replaced with pi-accepting pyridine
      groups (e.g., NN = phen, t1/2 = 9.5 h at 318 K). The OsII complexes hydrolyze up
      to 100 times more slowly than their RuII analogues. The pK*a of the aqua adducts
      decreased with a similar trend (pK*a = 6.3 and 5.8 for en and phen adducts,
      respectively). [(eta6-bip)Os(en)Cl]PF6/BF4 (1PF6/BF4) and [(eta6-THA)Os(en)Cl]BF4
      (2BF4) were cytotoxic toward both the human A549 lung and A2780 ovarian cancer
      cell lines, with IC50 values of 6-10 microM, comparable to the anticancer drug
      carboplatin. 1BF4 binds to both the N7 and phosphate of 5'-GMP (ratio of 2:1).
      The formation constant for the 9-ethylguanine (9EtG) adduct [(eta6
      bip)M(en)(9EtG)]2+ was lower for OsII (log K = 3.13) than RuII (log K = 4.78),
      although the OsII adduct showed some kinetic stability. DNA intercalation of the
      dppz ligand in 6PF6 may play a role in its cytotoxicity. This work demonstrates
      that the nature of the chelating ligand can play a crucial role in tuning the
      chemical and biological properties of [(eta6-arene)Os(NN)Cl]+ complexes.

PMID- 17441713
TI  - Remarkable steric effects and influence of monodentate axial ligands l on the
      spin-crossover properties of trans-[FeII(N4 ligand)L] complexes.
AB  - Iron(II) complexes obtained from tetradentate, rigid, linear N4 ligands have been
      investigated to appraise the influence of steric effects and the impact of trans
      coordinated anions on the spin-transition behavior. As expected, the well
      designed ligands embrace the metal center, resulting in octahedral iron(II)
      complexes where the basal plane is fully occupied by the pyridine/pyrazole N4
      ligand, while anions or solvent molecules are exclusively axially coordinated.
      Precursor complexes, namely, [Fe(bpzbpy)(MeOH)2](BF4)2 (where bpzbpy symbolizes
      the ligand 6,6'-bis(N-pyrazolylmethyl)-2,2'-bipyridine) and
      [Fe(mbpzbpy)(MeOH)2](BF4)2 (where mbpzbpy symbolizes the ligand 6,6'-bis(3,5
      dimethyl-N-pyrazolmethyl)-2,2'-bipyridine), have been used for the in situ
      preparation of a series of structural analogues via the exchange of the weakly
      coordinated trans methanol molecules by various anions, such as thiocyanate,
      selenocyanate, or dicyanamide. The magnetic properties of all seven iron(II)
      compounds thus obtained have been investigated. Two iron(II) complexes, i.e.,
      [Fe(bpzbpy)(NCS)2] and [Fe(bpzbpy)(NCSe)2], exhibit gradual spin-crossover (SCO)
      properties typical of isolated mononuclear species with weak cooperative
      interaction. These two SCO materials have been studied by Mossbauer spectroscopy,
      and the light-induced excited spin state trapping effect has been investigated,
      revealing the possibility to induce the spin-transition both by temperature
      variation and by light irradiation. A correlation between steric/anion effect and
      SCO behavior is suggested.

PMID- 17441714
TI  - Modification of spin crossover behavior through solvent assisted formation and
      solvent inclusion in a triply interpenetrating three-dimensional network.
AB  - The 3D coordination polymer [Fe(4ditz)3](PF6)2.solv consists of three
      interpenetrating infinite networks. There are cavities between iron atoms of
      different networks, which are partly filled with solvent molecules. With a change
      of the solvent used during synthesis from methanol to ethanol, the magnetic
      behavior of the materials changes. Both show an abrupt two-step spin crossover
      from low spin (S = 0) to high spin (S = 2) with the methanolate curve lying 7 K
      higher and showing a small hysteresis. Single crystal and powder diffraction
      studies show that they both have the same structure, but in powder form, the
      methanolate slowly loses methanol to finally leave about 0.075 MeOH/Fe. In
      comparison, the bigger ethanol remains at 0.25 EtOH/Fe. These results, in
      conjunction with thermodynamic data, strongly suggest that the differences in
      magnetic behavior are largely entropic in nature. Possible reasons for this are
      discussed.

PMID- 17441715
TI  - M2Ba2Sn6 (m =yb, ca): metallic zintl phases with a novel tin chain substructure.
AB  - The compounds M2Ba2Sn6 (M = Yb, Ca) have been synthesized by solid-state
      reactions in welded Ta tubes at high temperature. Their structures were
      determined by single-crystal X-ray diffraction studies to be orthorhombic; space
      group Cmca (No. 64); Z = 8; a = 15.871(3), 15.912 (3) A; b = 9.387(2), 9.497(2)
      A; c = 17.212(3), 17.184(3) A; and V = 2564.3(9), 2597.0(9) A3, respectively.
      These contain infinite tin chains along constructed from butterflylike 3-bonded
      Sn tetramers interconnected by pairs of 2-bonded Sn. The chains are further
      interconnected into corrugated layers by somewhat longer Sn-Sn bonds along c. The
      compounds with the chains alone would be Zintl phases, but the interchain bonding
      makes them formally one-electron rich per formula unit. The electronic structures
      calculated by extended Huckel and TB-LMTO-ASA methods indicate that these
      compounds are metallic but with a deep pseudogap at the Fermi level. States that
      bind the extra electrons lie just below EF and involve important Yb(Ca)-Sn
      contributions. The origin of metallic Zintl phases is briefly discussed.

PMID- 17441716
TI  - Mechanistic investigation of intramolecular aminoalkene and aminoalkyne
      hydroamination/cyclization catalyzed by highly electrophilic, tetravalent
      constrained geometry 4d and 5f complexes. Evidence for an M-N sigma-bonded
      insertive pathway.
AB  - A mechanistic study of intramolecular hydroamination/cyclization catalyzed by
      tetravalent organoactinide and organozirconium complexes is presented. A series
      of selectively substituted constrained geometry complexes, (CGC)M(NR2)Cl (CGC =
      [Me2Si(eta5-Me4C5)(tBuN)]2-; M = Th, 1-Cl; U, 2-Cl; R = SiMe3; M = Zr, R = Me, 3
      Cl) and (CGC)An(NMe2)OAr (An = Th, 1-OAr; An = U, 2-OAr), has been prepared via
      in situ protodeamination (complexes 1-2) or salt metathesis (3-Cl) in high purity
      and excellent yield and is found to be active precatalysts for intramolecular
      primary and secondary aminoalkyne and aminoalkene hydroamination/cyclization.
      Substrate reactivity trends, rate laws, and activation parameters for
      cyclizations mediated by these complexes are virtually identical to those of more
      conventional (CGC)MR2 (M = Th, R = NMe2, 1; M = U, R = NMe2, 2; M = Zr, R = Me,
      3), (Me2SiCp' '2)UBn2 (Cp' ' = eta5-Me4C5; Bn = CH2Ph, 4), Cp'2AnR2 (Cp' = eta5
      Me5C5; R = CH2SiMe3; An = Th, 5, U, 6), and analogous organolanthanide complexes.
      Deuterium KIEs measured at 25 degrees C in C6D6 for aminoalkene
      D2NCH2C(CH3)2CH2CHCH2 (11-d2) with precatalysts 2 and 2-Cl indicate that kH/kD =
      3.3(5) and 2.6(4), respectively. Together, the data provide strong evidence in
      these systems for turnover-limiting C-C insertion into an M-N(H)R sigma-bond in
      the transition state. Related complexes (Me2SiCp' '2)U(Bn)(Cl) (4-Cl) and
      Cp'2An(R)(Cl) (R = CH2(SiMe3); An = Th, 5-Cl; An = U, 6-Cl) are also found to be
      effective precatalysts for this transformation. Additional arguments supporting M
      N(H)R intermediates vs M=NR intermediates are presented.

PMID- 17441717
TI  - Janus discs.
AB  - We describe the synthesis and the solution properties of sheet- and disclike
      Janus particles, containing an inner crosslinked polybutadiene (PB) layer and two
      different outer sides of polystyrene (PS) and poly(tert-butyl methacrylate)
      (PtBMA). The structures formed upon adsorption of the flat Janus particles onto
      solid substrates as well as in THF solution are investigated. The Janus discs are
      obtained in a template-assisted synthetic pathway followed by sonication.
      Selectively crosslinking the lamellar PB domains in a well-ordered lamellar
      microphase-separated bulk morphology of PS-block-PB-block-PtBMA (SBT) block
      terpolymers leads to the conservation of the compartmentalization of the two
      outer blocks. Sonication of the crosslinked block terpolymer templates renders
      soluble sheet- and disclike Janus particles, the size of which can be tuned from
      the micrometer range down to the nanometer scale. Small-angle X-ray scattering,
      transmission electron microscopy, dynamic light scattering, scanning force
      microscopy, and scanning electron microscopy are used to characterize the
      template-assisted synthetic process and the solution properties. Cryogenic
      transmission electron microscopy in THF and TEM of particles, embedded into a
      photo-crosslinkable silicon oil, indicate a supramolecular aggregation behavior
      of the Janus discs in concentrated solutions. Pendant drop tensiometry
      demonstrates that Janus sheets and discs can be used to stabilize liquid-liquid
      interfaces, rendering these materials interesting for future applications.

PMID- 17441718
TI  - Proton assisted oxygen-oxygen bond splitting in cytochrome p450.
AB  - Proton assisted O-O bond splitting of cytochromes' P450 hydroperoxo Compound 0
      has been investigated by density functional theory, showing a barrier for the
      slightly endothermic formation of the iron-oxo Compound I. The barrier and the
      endothermicity increase with decreasing acidity of the distal proton source.
      Protonation of the proximal iron heme ligand favors the O-O bond scission and
      provides an important regulatory component in the catalytic cycle. The Compound 0
      --> I conversion is slightly exothermic for the peroxidase and catalase models.
      Implications of the energetic relationship between the two reactive intermediates
      are discussed in terms of possible oxidative pathways.

PMID- 17441719
TI  - Fe2+ catalyzes vitamin E-induced fragmentation of hydroperoxy and hydroxy
      endoperoxides that generates gamma-hydroxy alkenals.

PMID- 17441720
TI  - Enhancement of cyclopropanation chemistry in the silver-catalyzed reactions of
      aryldiazoacetates.

PMID- 17441721
TI  - Design of a hybrid biosensor for enhanced phosphopeptide recognition based on a
      phosphoprotein binding domain coupled with a fluorescent chemosensor.
AB  - Protein-based fluorescent biosensors with sufficient sensing specificity are
      useful analytical tools for detection of biologically important substances in
      complicated biological systems. Here, we present the design of a hybrid
      biosensor, specific for a bis-phosphorylated peptide, based on a natural
      phosphoprotein binding domain coupled with an artificial fluorescent chemosensor.
      The hybrid biosensor consists of a phosphoprotein binding domain, the WW domain,
      into which has been introduced a fluorescent stilbazole having Zn(II)
      dipicolylamine (Dpa) as a phosphate binding motif. It showed strong binding
      affinity and high sensing selectivity toward a specific bis-phosphorylated
      peptide in the presence of various phosphate species such as the
      monophosphorylated peptide, ATP, and others. Detailed fluorescence titration
      experiments clearly indicate that the binding-induced fluorescence enhancement
      and the sensing selectivity were achieved by the cooperative action of both
      binding sites of the hybrid biosensor, i.e., the WW domain and the Zn(II)-Dpa
      chemosensor unit. Thus, it is clear that the tethered Zn(II)-Dpa-stilbazole unit
      operated not only as a fluorescence signal transducer, but also as a sub-binding
      site in the hybrid biosensor. Taking advantage of its selective sensing property,
      the hybrid biosensor was successfully applied to real-time and label-free
      fluorescence monitoring of a protein kinase-catalyzed phosphorylation.

PMID- 17441723
TI  - Nickel-catalyzed regio- and stereoselective silylation of terminal alkenes with
      silacyclobutanes: facile access to vinylsilanes from alkenes.

PMID- 17441724
TI  - Isolable silylene anion radical: structural characteristics in the solid state
      and in solution.

PMID- 17441722
TI  - Computational design and experimental discovery of an antiestrogenic peptide
      derived from alpha-fetoprotein.
AB  - Breast cancer is the most common cancer among women, and tamoxifen is the
      preferred drug for estrogen receptor-positive breast cancer treatment. Many of
      these cancers are intrinsically resistant to tamoxifen or acquire resistance
      during treatment. Consequently, there is an ongoing need for breast cancer drugs
      that have different molecular targets. Previous work has shown that 8-mer and
      cyclic 9-mer peptides inhibit breast cancer in mouse and rat models, interacting
      with an unsolved receptor, while peptides smaller than eight amino acids did not.
      We show that the use of replica exchange molecular dynamics predicts the
      structure and dynamics of active peptides, leading to the discovery of smaller
      peptides with full biological activity. Simulations identified smaller peptide
      analogues with the same conserved reverse turn demonstrated in the larger
      peptides. These analogues were synthesized and shown to inhibit estrogen
      dependent cell growth in a mouse uterine growth assay, a test showing reliable
      correlation with human breast cancer inhibition.

PMID- 17441725
TI  - Two-dimensional assembly of rod amphiphiles into planar networks.

PMID- 17441726
TI  - Gated photochromism of 1,2-diarylethenes.
AB  - A dithienylethene derivative containing a cyclobutene-1,2-dione skeleton does not
      exhibit photochromic properties. However, when both ketone functions are
      protected with cyclic acetal groups, photochromic behavior is observed.

PMID- 17441727
TI  - Palladium-catalyzed carbene insertion into vinyl halides and trapping with
      amines.
AB  - Palladium is shown to catalyze the three-component coupling of vinyl halides,
      trimethylsilyldiazomethane, and amines to generate allylamines. The mechanism is
      believed to involve formation of an R-Pd=CHSiMe3 intermediate that undergoes
      migration of the vinyl ligand to the empty p-orbital of the carbene ligand. The
      resulting eta1-allylpalladium species forms an eta3-allylpalladium intermediate
      that is trapped by the amine nucleophile. Under the conditions tested, cyclic
      secondary amines and terminal vinyl iodides give the best results.

PMID- 17441728
TI  - Spectrophotometric determination of phenolic compounds by enzymatic and chemical
      methods--a comparison of structure--activity relationship.
AB  - A spectrophotometric determination of phenolic compounds by a peroxidase
      catalyzed enzymatic (PE) method and the Folin-Ciocalteu (FC) chemical method was
      compared for their structure-activity relationship. In the PE method, the
      reaction time of 19 phenolic compounds with different chemical structures was
      found to be within 15 min, with those having bulky substituents showing slower
      reactivity. The responses of the phenolic compounds toward the PE method in terms
      of molar absorbance were positively correlated with the nucleophilicity of their
      corresponding phenoxyl radicals. An increase in the nucleophilicity by
      substitution of methoxyl and hydroxyl (electron-donating) groups enhanced the
      responses; while a decrease in nucleophilicity by substitution of the allyl
      carboxylic (electron-withdrawing) groups lowered the responses of phenolic
      compounds toward the enzymatic assay. The responses of phenolic compounds to the
      enzymatic method were found to be independent of the degree of hydroxylation
      while those to the FC assay were affected by both the position and degree of
      hydroxylation. Interfering chemicals found in the FC assay, including vitamin C,
      6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (a vitamin E analogue),
      and tert-butylhydroquinone (a commercial antioxidant) were insensitive to the
      enzymatic assay. The PE method appears to have a higher specificity toward
      phenolic compounds and subject to less interferences from other antioxidants than
      the FC method.

PMID- 17441729
TI  - NMR solution structure of neurotensin in membrane-mimetic environments: molecular
      basis for neurotensin receptor recognition.
AB  - Neurotensin (NT) is a 13-residue neuropeptide that exerts multiple biological
      functions in the central and peripheral nervous system. Little is known about the
      structure of this neuropeptide, and what is known only concerns its C-terminal
      part. We determined here for the first time the structure of the full-length NT
      in membrane-mimicking environments by means of classical proton-proton distance
      constraints derived from solution-state NMR spectroscopy. NT was found to have a
      structure at both its N and C termini, whereas the central region of NT remains
      highly flexible. In TFE and HFIP solutions, the NT C-terminus presents an
      extended slightly incurved structure, whereas in DPC it has a beta turn. The N
      terminal region of NT possesses great adaptability and accessibility to the
      microenvironment in the three media studied. Altogether, our work demonstrates a
      structure of NT fully compatible with its NTR-bound state.

PMID- 17441730
TI  - Cofactor-directed reversible denaturation pathways: the cofactor-stabilized
      Escherichia coli aspartate aminotransferase homodimer unfolds through a pathway
      that differs from that of the apoenzyme.
AB  - While the urea-mediated unfolding pathway of the Escherichia coli aspartate
      aminotransferase (eAATase) homodimer proceeds through a reversible three-state
      process with a partially folded dimeric intermediate, D D* 2U (E. Deu and J. F.
      Kirsch, accompanying paper), that of a cofactor-stabilized form differs.
      Pyridoxal phosphate, which binds at the intersubunit active sites, stabilizes the
      native form by 6 kcal mol-1 and dissociates during the D <==> D* transition.
      Reductive trapping of the cofactor to a nondissociable derivative (PPL-eAATase)
      precludes the formation of D*. A novel monomeric intermediate (M'-PPL) with 70%
      of the native secondary structure (circular dichroism) was identified in the
      unfolding pathway of PPL-eAATase: D-PPL2 <==> 2M'-PPL <==> 2U-PPL. The combined
      results define two structural regions with distinct stabilities: the active site
      region (ASR) and the generally more stable, dimerization region (DMR). The DMR
      includes the key intersubunit contacts. It is responsible for the multimeric
      nature of D*, and its disorder leads to dimer dissociation. Selective
      strengthening of the ASR-cofactor interactions by cofactor trapping reverses the
      relative stabilities of the two regions (from DMR > ASR in the apoenzyme to ASR >
      DMR in PPL-eAATase) and results in a reordering of the eAATase denaturation
      pathway.

PMID- 17441731
TI  - Phosphorylation of RNA helicase A by DNA-dependent protein kinase is
      indispensable for expression of the MDR1 gene product P-glycoprotein in multidrug
      resistant human leukemia cells.
AB  - Development of multidrug resistance (MDR) in cancer frequently involves
      overexpression of the MDR1 gene product P-glycoprotein (P-gp), a drug transporter
      which severely impedes the efficacy of chemotherapy. Because intensive efforts to
      identify therapeutics that reverse MDR by inhibiting the drug transport activity
      of P-gp have not yet met with success, we have focused on the alternative
      strategy of targeting MDR1 promoter activation to knockdown P-gp expression in
      cancer cells. We recently identified RNA helicase A (RHA) inhibition as a
      rational strategy to downregulate P-gp in leukemia cells by showing that RHA RNAi
      knockdown abrogated P-gp expression in MDR variants of human leukemia HL-60
      cells. In that report, we also demonstrated that RHA activated the MDR1 promoter
      in the MDR variant cells but not in the drug-sensitive counterpart. This led us
      to hypothesize that P-gp induction by RHA required cooperation with another
      factor present only in the MDR variants. Here, we identify the RHA cooperating
      factor as DNA-PK catalytic subunit (cs), and we show that DNA-PKcs resides with
      RHA at the MDR1 promoter in a multiprotein complex. Furthermore, targeted DNA
      PKcs inhibition abrogated P-gp expression in the MDR variant cells. We
      demonstrate that constitutive multisite RHA phosphorylation producing retarded
      migration in SDS-PAGE is catalyzed by DNA-PKcs in the MDR variants, and does not
      occur in the parental cells, which are DNA-PKcs deficient. The indispensable role
      played by DNA-PK in P-gp overexpression in MDR leukemia cells in this report
      identifies targeted DNA-PK inhibition as a rational strategy to reverse drug
      resistance in cancer.

PMID- 17441732
TI  - Crystal structure of a hyperactive Escherichia coli glycerol kinase mutant Gly230
      --> Asp obtained using microfluidic crystallization devices.
AB  - The crystal structure of an Escherichia coli glycerol kinase mutant Gly230 -->
      Asp (GKG230D) was determined to 2.0 A resolution using a microfluidics based
      crystallization platform. The crystallization strategy involved a suite of
      microfluidic devices that characterized the solubility trends of GKG230D,
      performed nanoliter volume free interface diffusion crystallization experiments,
      and produced diffraction-quality crystals for in situ data collection. GKG230D
      displays increased enzymatic activity and decreased allosteric regulation by the
      glycolytic pathway intermediate fructose 1,6-bisphosphate (FBP) compared to wild
      type GK (GKWT). Structural analysis revealed that the decreased allosteric
      regulation is a result of the altered FBP binding loop conformations in GKG230D
      that interfere with the wild-type FBP binding site. The altered FBP binding loop
      conformations in GKG230D are supported through a series of intramolecular loop
      interactions. The appearance of Asp230 in the FBP binding loops also repositions
      the wild-type FBP binding residues away from the FBP binding site. Light
      scattering analysis confirmed GKG230D is a dimer and is resistant to tetramer
      formation in the presence of FBP, whereas GKWT dimers are converted into
      putatively inactive tetramers in the presence of FBP. GKG230D also provides the
      first structural evidence for multiple GK monomer conformations in the presence
      of glycerol and in the absence of a nucleotide substrate and verifies that
      glycerol binding is not responsible for locking GK into the closed conformation
      necessary for GK activity.

PMID- 17441733
TI  - Cysteine reactivity and thiol-disulfide interchange pathways in AhpF and AhpC of
      the bacterial alkyl hydroperoxide reductase system.
AB  - AhpC and AhpF from Salmonella typhimurium undergo a series of electron transfers
      to catalyze the pyridine nucleotide-dependent reduction of hydroperoxide
      substrates. AhpC, the peroxide-reducing (peroxiredoxin) component of this alkyl
      hydroperoxidase system, is an important scavenger of endogenous hydrogen peroxide
      in bacteria and acts through a reactive, peroxidatic cysteine, Cys46, and a
      second cysteine, Cys165, that forms an active site disulfide bond. AhpF, a
      separate disulfide reductase protein, regenerates AhpC every catalytic cycle via
      electrons from NADH which are transferred to AhpC through a tightly bound flavin
      and two disulfide centers, Cys345-Cys348 and Cys129-Cys132, through putative
      large domain movements. In order to assess cysteine reactivity and interdomain
      interactions in both proteins, a comprehensive set of single and double cysteine
      mutants (replacing cysteine with serine) of both proteins were prepared. Based on
      5,5-dithiobis(2-nitrobenzoic acid) (DTNB) and AhpC reactivity with multiple
      mutants of AhpF, the thiolate of Cys129 in the N-terminal domain of AhpF
      initiates attack on Cys165 of the intersubunit disulfide bond within AhpC for
      electron transfer between proteins. Cys348 of AhpF has also been identified as
      the nucleophile attacking the Cys129 sulfur of the N-terminal disulfide bond to
      initiate electron transfer between these two redox centers. These findings
      support the modular architecture of AhpF and its need for domain rotations for
      function, and emphasize the importance of Cys165 in the reductive reactivation of
      AhpC. In addition, two new constructs have been generated, an AhpF-AhpC complex
      and a "twisted" form of AhpF, in which redox centers are locked together by
      stable disulfide bonds which mimic catalytic intermediates.

PMID- 17441734
TI  - Crystal structure of KPC-2: insights into carbapenemase activity in class A beta
      lactamases.
AB  - Beta-lactamases inactivate beta-lactam antibiotics and are a major cause of
      antibiotic resistance. The recent outbreaks of Klebsiella pneumoniae carbapenem
      resistant (KPC) infections mediated by KPC type beta-lactamases are creating a
      serious threat to our "last resort" antibiotics, the carbapenems. KPC beta
      lactamases are serine carbapenemases and are a subclass of class A beta
      lactamases that have evolved to efficiently hydrolyze carbapenems and cephamycins
      which contain substitutions at the alpha-position proximal to the carbonyl group
      that normally render these beta-lactams resistant to hydrolysis. To investigate
      the molecular basis of this carbapenemase activity, we have determined the
      structure of KPC-2 at 1.85 A resolution. The active site of KPC-2 reveals the
      presence of a bicine buffer molecule which interacts via its carboxyl group with
      conserved active site residues S130, K234, T235, and T237; these likely resemble
      the interactions the beta-lactam carboxyl moiety makes in the Michaelis-Menten
      complex. Comparison of the KPC-2 structure with non-carbapenemases and previously
      determined NMC-A and SME-1 carbapenemase structures shows several active site
      alterations that are unique among carbapenemases. An outward shift of the
      catalytic S70 residue renders the active sites of the carbapenemases more
      shallow, likely allowing easier access of the bulkier substrates. Further space
      for the alpha-substituents is potentially provided by shifts in N132 and N170 in
      addition to concerted movements in the postulated carboxyl binding pocket that
      might allow the substrates to bind at a slightly different angle to accommodate
      these alpha-substituents. The structure of KPC-2 provides key insights into the
      carbapenemase activity of emerging class A beta-lactamases.

PMID- 17441736
TI  - Thermophysical properties of interfacial layer in nanofluids.
AB  - Although recent experiments have revealed that nanofluids have superior thermal
      conductivities to base fluids, the inherent physics are not fully understood. In
      this study, an interfacial layer, competing with Brownian motion as a
      corresponding mechanism, is conceptually connected with the surface-charge
      induced electrical double layer. By applying colloidal science, the first
      explicit equations for the thickness and thermal conductivity of the layer are
      obtained. A fractal model including the new concept of the layer is developed.
      The model predictions are compared with experimental data for effects of pH,
      temperature, volume fraction, and primary particle size of CuO-water nanofluids.

PMID- 17441735
TI  - DNA interstrand cross-linking by epichlorohydrin.
AB  - Epichlorohydrin (ECH), an important industrial chemical, is a bifunctional
      alkylating agent with the potential to form DNA cross-links. Occupational
      exposure to this suspect carcinogen leads to chromosomal aberrations, and ECH has
      been shown previously to undergo reaction with DNA in vivo and in vitro. We used
      denaturing polyacrylamide gel electrophoresis to monitor the possible formation
      of interstrand cross-links within DNA oligomers by ECH and the related compound,
      epibromohydrin (EBH). Although both compounds did indeed form cross-links between
      deoxyguanosine residues, EBH was a more efficient cross-linker than ECH. The
      optimal pH for cross-linking also varied, with ECH more efficient at pH 5.0 and
      EBH more efficient at pH 7.0. Both agents were relatively flexible in the
      sequences targeted, with comparable efficiencies for 5'-GGC and 5'GC sites.
      Furthermore, interstrand cross-linking by the two optical isomers of ECH
      correlated with their relative cytotoxicities, with R-ECH about twice as potent
      as S-ECH.

PMID- 17441737
TI  - Interactions between gemini surfactants and polymers: thermodynamic studies.
AB  - Aqueous mixtures containing a homopolymer, poly(vinylpyrrolidone) (PVP), or a
      hydrophobically modified graft copolymer, HM-pullulan, (PULAU9, where 9 stands
      for the nominal substitution degree), and different Gemini surfactants have been
      investigated at 25.0 degrees C. A wide variety of experimental conditions were
      addressed by changing the amount of polymer and of surfactant. The Gemini
      surfactants were synthesized, purified, and characterized by routine methods.
      They differ from each other in polar head groups (two sulfonate-, two quaternary
      ammonium-, or two arginine-based groups), in alkyl chain length (11 or 12 carbon
      atoms), and in the distance between the polar head groups. The spacers consist of
      2, 3, and 6 methylene units or 3 oxyethylene units. Surface activity and solution
      calorimetry measurements yield some physicochemical features inherent to micelle
      formation and polymer-surfactant interactions. The data are supported by ionic
      conductivity, detecting the critical thresholds and quantifying the modifications
      in binding associated with critical association (CAC) and micelle formation
      (CMC*). The Gibbs energy of transfer from the micelles to a polymer-binding site,
      DeltaGtrans, was evaluated from the CAC/CMC* ratios versus the amount of added
      polymer. A similar procedure determined the enthalpy of transfer, DeltaHtrans.
      DeltaGtrans decreases with added polymer, whereas DeltaHtrans becomes more
      negative on increasing the amount of polymer in the medium. According to the
      selected data presented here, cationic Geminis do not interact with PVP, while
      significant interactions have been observed in other surfactants. In mixtures
      with PULAU9, the interaction is significant for all Geminis. This effect is due
      to interactions between the surfactants and the hydrophobic alkyl groups on the
      main polymer chain. The pendent groups facing away from the polysaccharide chain
      act as binding sites for aggregates onto such polymers.

PMID- 17441738
TI  - Imaging photoelectron transmission through self-assembled monolayers: the work
      function of alkanethiols coated gold.
AB  - In this paper, we present a new approach for studying the electronic properties
      of self-assembled monolayers and their interaction with a conductive substrate,
      the low-energy photoelectron imaging spectroscopy (LEPIS). LEPIS relies on
      imaging of photoelectrons ejected from a conductive substrate and subsequently
      transmitted through organic monolayers. Using this method, we measure the
      relative work-function of alkanethiols of different length on gold substrate, and
      we are able to follow the changes occurring when the surface coverage is varied.
      We also computed the work-function of model alkanethiols using a plane-wave
      density functional theory approach, in order to demonstrate the correlation
      between changes in the work-function with the monolayer organization and density.

PMID- 17441739
TI  - Revisiting the morphology development of solvent-swollen composite polymer
      particles at thermodynamic equilibrium.
AB  - Morphology of polystyrene (PS)/poly(methyl methacrylate) (PMMA)/toluene droplets,
      in which phase separation proceeds, dispersed in SDS aqueous solution was
      examined. It changed from ex-centered PS-core/PMMA-shell to hemisphere with
      increasing SDS concentration. At low polymer weight fraction (wp), PS and PMMA
      phases contained non-negligible amount of PMMA and PS, respectively. The small
      amount of PS and PMMA in PMMA and PS phases, respectively, affected significantly
      the interfacial tension between polymer/toluene and aqueous solutions.
      Interfacial tension between PS and PMMA phases at low wp was measured by the
      spinning drop method, showing a quite low value ( approximately 10-2 mN/m).
      Predicted morphology obtained from calculation of minimum total interfacial free
      energy of the droplets using the interfacial tensions agreed well with the
      experimental observation.

PMID- 17441740
TI  - Reversible disulfide cross-linking in layer-by-layer films: preassembly enhanced
      loading and pH/reductant dually controllable release.
AB  - This paper describes the fabrication of polyelectrolyte multilayer film which
      combines preassembly of poly(allylamine hydrochloride) (PAH) and 5,10,15,20
      tetraphenyl-21H,23H-porphine-p,p',p' ',p' ''-tetrasulfonic acid tetrasodium
      hydrate (TPPS) in aqueous solution with the layer-by-layer (LbL) assembly of the
      PAH-TPPS complex and cross-linkable polyelectrolyte, PAASH60, which is a
      poly(acrylic acid) with 60% of its carboxylic acid grafted of thiol groups.
      During preassembly, TPPS was incorporated into PAH chains. After oxidative cross
      linking to form disulfide bonds in between the layers, the multilayer with
      preassembly of the PAH-TPPS complex allowed for release and loading of TPPS in a
      reproducible way. The release of TPPS from the loaded film was a pH-controlled
      process. To compare with the conventional multilayer, the reloading capacity was
      greatly enhanced, which was related to the charge binding sites that formed by
      release of TPPS from the multilayer. Moreover, the release of TPPS could also be
      achieved by breaking off the cross-linking through reduction of disulfide bonds,
      and the release rates could be controlled by the reductive efficiency of the
      reductants in the media. In this way, the release of TPPS is pH/reductant dually
      controllable, thereby facilitating a new route to multistimuli controllable
      materials.

PMID- 17441741
TI  - Single molecule force spectroscopy of asphaltene aggregates.
AB  - Asphaltene aggregation and deposition cause severe problems in nearly all phases
      of petroleum processing. To resolve those problems, understanding the aggregation
      mechanisms is a prerequisite and has attracted the interest of a great number of
      investigators. However, to date, the nature and extent of asphaltene aggregation
      remain widely debated. In the present study, we attempt to investigate asphaltene
      aggregation from a completely new perspective. The technique of single molecule
      force spectroscopy (SMFS) was used to investigate the response of single
      asphaltene aggregates under an external pulling force. Force curves representing
      the stretching of single asphaltene aggregates were obtained in simple
      electrolyte solutions (KCl and calcium) and organic solvents (toluene and
      heptane). These force curves were well-fitted by the modified worm-like chain
      model, indicating that those asphaltene aggregates acted like long-chain polymers
      under pulling by an external force. It was found that lower solution pH values
      and the presence of divalent cations resulted in a lower bending rigidity of the
      formed aggregates. The information retrieved from the force curves suggests that
      asphaltene molecules with a structure featuring small aromatic clusters connected
      by aliphatic chains do exist and that asphaltene aggregation could occur through
      a linear polymerization mechanism. The current study extends the application
      scope of SMFS.

PMID- 17441742
TI  - Oxygen reduction activity of carbon-supported Pt-M (M = V, Ni, Cr, Co, and Fe)
      alloys prepared by nanocapsule method.
AB  - Monodispersed Pt and Pt-M (M = V, Cr, Fe, Co, and Ni) alloy nanoparticles
      supported on carbon black (denoted as Pt/CB and Pt-M/CB) were prepared by the
      simultaneous reduction of platinum acetylacetonate and the second metal
      acetylacetonate within nanocapsules formed in diphenyl ether in the presence of
      carbon black. For the Pt/CBs, the average Pt diameters measured by scanning
      transmission electron microscopy (STEM) or X-ray diffraction (XRD) ranged from
      2.0 to 2.5 nm, regardless of the catalyst-loading level from 10 to 55 wt % on CB.
      The alloy composition was found to be well-controlled to the projected value
      among the supported particles. The activities for the oxygen reduction reaction
      (ORR) at Nafion-coated catalysts in O2-saturated 0.1 M HClO4 solution were
      evaluated by using a channel flow electrode (CFE) cell at 30 degrees C. The area
      specific ORR activities at Pt-M/CB were found to be 1.3 to 1.8 times higher than
      that at Pt/CB. The ORR activity increased in the order Pt/CB < Pt-Ni/CB < Pt
      Fe/CB < Pt-Co/CB < Pt-V/CB < Pt-Cr/CB.

PMID- 17441743
TI  - Cooperative ordering of collagen triple helices in the dense state.
AB  - Extracellular matrixes such as bone, skin, cornea, and tendon have ordered
      structures comprised for the most part of collagen, an elongated protein of well
      defined dimensions and composition. Here we show how the cooperative ordering of
      collagen triple helices in the dense fluid state is exploited to produce dense
      ordered collagen matrixes. The spontaneous formation of a birefringent phase
      occurs at critical concentrations that increase from 50-60 to 80-85 mg/mL as the
      acetic acid concentration of the solvent increases from 5 to 500 mM. We studied
      by small-angle X-ray scattering (SAXS) the local liquidlike positional order
      across the isotropic/anisotropic phase transition by unwinding the cholesteric
      phase with moderate shearing stress. Interparticle scattering gives rise to a
      broad interference peak. The average distance between triple helices, dav, is
      thus estimated and decreases linearly as a function of phi-1/2 from 12.7 +/- 0.9
      nm (22.5 mg/mL) to 5.0 +/- 0.6 nm (166.4 mg/mL). Equilibrium concentrations and
      the order parameter of the nematic phase agree reasonably well with theoretical
      predictions for semiflexible macromolecules. Striated fibrils with a high degree
      of alignment were obtained by fine-tuning the delicately balanced electrostatic
      interactions, which yielded strong elastic gels with a hierarchical organization
      very similar to that of major biological tissues. Typical Bragg reflections
      corresponding to the 67 nm period characteristic of collagen fibrils in
      biological tissues were recorded by SAXS with ordered collagen matrixes
      reconstituted in vitro.

PMID- 17441744
TI  - Binding of glycine and L-cysteine on Si(111)-7 x 7.
AB  - The adsorption of glycine and l-cysteine on Si(111)-7 x 7 was investigated using
      high-resolution electron energy loss spectroscopy (HREELS) and X-ray
      photoelectron spectroscopy (XPS). The observation of the characteristic
      vibrational modes and electronic structures of NH3+ and COO- groups for
      physisorbed glycine (l-cysteine) demonstrates the formation of zwitterionic
      species in multilayers. For chemisorbed molecules, the appearance of nu(Si-H),
      nu(Si-O), and nu(C=Omicron) and the absence of nu(O-H) clearly indicate that
      glycine and l-cysteine dissociate to produce monodentate carboxylate adducts on
      Si(111)-7 x 7. XPS results further verified the coexistence of two chemisorption
      states for each amino acid, corresponding to a Si-NH-CH2-COO-Si [Si
      NHCH(CH2SH)COO-Si] species with new sigma-linkages of Si-N and Si-O, and a NH2
      CH2-COO-Si [NH2CH(CH2SH)COO-Si] product through the cleavage of the O-H bond,
      respectively. Glycine/Si(111)-7 x 7 and l-cysteine/Si(111)-7 x 7 can be viewed as
      model systems for further modification of Si surfaces with biological molecules.

PMID- 17441745
TI  - Size-Exclusion "capture and release" separations using surface-patterned poly(N
      isopropylacrylamide) hydrogels.
AB  - Micrometer-scale poly(N-isopropylacrylamide) (poly-NIPAAm) hydrogel monolith
      patterns were fabricated on solid surfaces using soft lithography. At
      sufficiently high aspect ratios, the hydrogel monoliths swell and contract
      laterally with temperature. The spaces between the monoliths form a series of
      trenches that catch, hold, and release appropriately sized targets. A series of
      poly-NIPAAm monoliths were fabricated with dry dimensions of 40 microm height, 12
      microm diameter, and a spacing of 12 microm between monoliths. Above the lower
      critical solution temperature (LCST), the monoliths collapse to their dry
      dimensions and the spacing between monoliths is 12 microm. Below the LCST, the
      monoliths swell by 70% in the lateral direction, reducing the gap size between
      monoliths to 3 microm. The potential use of the hydrogel monoliths as size
      selective "catch and release" structures was demonstrated with a mixture of 6 and
      20 microm polystyrene microspheres, where the 6 microm diameter particles were
      selectively concentrated and separated from the larger particles.

PMID- 17441746
TI  - Examining the accuracy of ideal adsorbed solution theory without curve-fitting
      using transition matrix Monte Carlo simulations.
AB  - Ideal adsorbed solution theory (IAST) is a well-known approach to predicting
      multicomponent adsorption isotherms in microporous materials from experimental or
      simulation data for single-component adsorption. A limitation in practical
      applications of IAST is that useful calculations often require extrapolation of
      fitted single-component isotherms beyond the range for which data are available.
      We introduce a molecular simulation approach in which the intrinsic accuracy of
      IAST can be examined in a context that avoids any need to perform curve fitting
      with single-component data. Our approach is based on using transition matrix
      Monte Carlo to define single-component adsorption isotherms for arbitrary bulk
      phase pressures from a single simulation. We apply our approach to several light
      gas mixtures in silica zeolites and a carbon nanotube to examine the intrinsic
      accuracy of IAST for these model systems.

PMID- 17441747
TI  - A new algorithm using cross-assignment for label-free quantitation with LC-LTQ-FT
      MS.
AB  - A new algorithm is described for label-free quantitation of relative protein
      abundances across multiple complex proteomic samples. Q-MEND is based on the
      denoising and peak picking algorithm, MEND, previously developed in our
      laboratory. Q-MEND takes advantage of the high resolution and mass accuracy of
      the hybrid LTQ-FT MS mass spectrometer (or other high-resolution mass
      spectrometers, such as a Q-TOF MS). The strategy, termed "cross-assignment", is
      introduced to increase substantially the number of quantitated proteins. In this
      approach, all MS/MS identifications for the set of analyzed samples are combined
      into a master ID list, and then each LC-MS run is searched for the features that
      can be assigned to a specific identification from that master list. The
      reliability of quantitation is enhanced by quantitating separately all peptide
      charge states, along with a scoring procedure to filter out less reliable peptide
      abundance measurements. The effectiveness of Q-MEND is illustrated in the
      relative quantitative analysis of Escherichia coli samples spiked with known
      amounts of non-E. coli protein digests. A mean quantitation accuracy of 7% and
      mean precision of 15% is demonstrated. Q-MEND can perform relative quantitation
      of a set of LC-MS data sets without manual intervention and can generate files
      compatible with the Guidelines for Proteomic Data Publication.

PMID- 17441748
TI  - Increased coverage in the transmembrane domain with activated-ion electron
      capture dissociation for top-down Fourier-transform mass spectrometry of integral
      membrane proteins.
AB  - The c-subunit of ATP synthase (AtpH) is an 8 kD integral membrane protein with
      two transmembrane domains; we set out to demonstrate it amenable to top-down
      electrospray-ionization Fourier-transform mass spectrometry (FT-MS) using both
      collision activated and electron capture dissociation (CAD/ECD). Thermal
      activation concomitant with electron delivery was necessary for efficient ECD
      (activated-ion ECD; aiECD), yielding complementary information and greater
      sequence coverage in the transmembrane domains in comparison with CAD.

PMID- 17441750
TI  - Structure and orientation of the imidazolium cation at the room-temperature ionic
      liquid/SiO2 interface measured by sum-frequency vibrational spectroscopy.
AB  - In this study, we have examined both the effect of alkyl chain length and anion
      composition on the 1-alkyl-3-methylimidazolium (C(n)mim, n = 4, 6, 8, 10, and 12)
      structure and orientation at the room-temperature ionic liquid (RTIL)/SiO(2)
      interface by sum-frequency vibrational spectroscopy (SFVS). Four different anions
      were investigated in this study: tetrafluoroborate (BF(4)), hexafluorophosphate
      (PF(6)), bis(trifluoromethylsulfonyl)imide (BMSI), and
      bis(pentafluoroethylsulfonyl)imide (BETI). It was found that the alkyl chain in
      BMSI and BETI RTILs showed a decrease in gauche defects with an increase in chain
      length, whereas the alkyl chains of the BF(4) and PF(6) RTILs have virtually no
      gauche defects regardless of chain length. The tilt of the alkyl chain lies
      predominantly perpendicular to the surface for all the RTILs examined. A strong
      correlation between the HCCH vs tilt angle and alkyl chain length was observed;
      as the alkyl chain is lengthened the HCCH vs lies more perpendicular to the
      SiO(2) surface. The results of this study suggest that the length of the alkyl
      chain dictates to a large degree the orientation of the imidazolium cation at the
      surface, regardless of anion composition. To a lesser extent, the HCCH vs tilt of
      the imidazolium ring of the cation also appears to be correlated to the surface
      charge density of the SiO(2). As the SiO(2) surface charge density becomes more
      negative the HCCH vs tilt angle lies more parallel to the surface.

PMID- 17441749
TI  - Attachment of LcrV from Yersinia pestis at dual binding sites to human TLR-2 and
      human IFN-gamma receptor.
AB  - The virulence antigen (V-antigen, LcrV) of Yersinia pestis, the causative agent
      of bubonic plague, is an established protective antigen known to regulate,
      target, and mediate type III translocation of cytotoxic yersiniae outer proteins
      termed Yops; LcrV also prompts TLR2-dependent upregulation of anti-inflammatory
      IL-10. In this study, we determined the parameters of specific interaction of
      LcrV with TLR2 expressed on human transfected HEK293 cells (TLR2+/CD14-),
      VTEC2.HS cells (TLR2+/CD14-), primary monocytes (TLR2+/CD14+), and THP-1 cells
      (TLR2+/CD14+). The IRRL314-317 motif of the extracellular domain of human and
      mouse TLR2 accounted for high-affinity binding of LcrV. The CD14 co-receptor did
      not influence this interaction. LcrV did not bind to human U937 (TLR2-/CD14-) and
      alveolar macrophages (TLR2-/CD14+) in the absence of receptor-bound human IFN
      gamma or a synthetic C-terminal fragment (hIFN-gamma132-143). The latter, but not
      mouse IFN-gamma (or synthetic control peptides), shared a GRRA138-141 site
      necessary for high-affinity specific binding. LcrV of Y. pestis shares the N
      terminal LEEL32-35 binding site of Yersinia enterocolitica and also has an
      exposed internal DEEI203-206 binding site. Comparison of binding constants and
      consideration of steric restrictions indicate that binding is not cooperative and
      only the internal site binds LcrV to target cells. Both the LEEL32-35 and DEEI203
      206 binding sites are removed by five amino acids from DKN residues associated
      with biological activity of bound LcrV. LcrV of Y. pestis promoted both TLR2/CD14
      dependent and TLR2/CD14-independent amplification of IL-10 and concomitant
      downregulation of TNF-alpha in human target cells. The ability of LcrV to utilize
      human IFN-gamma (a major inflammatory effector of innate immunity) to minimize
      inflammation is insidious and may account in part for the severe symptoms of
      plague in man.

PMID- 17441751
TI  - Polyion complex nanomaterials from block polyelectrolyte micelles and linear
      polyelectrolytes of opposite charge: 1. Solution behavior.
AB  - The present study investigates whether block polyelectrolyte micelles can form
      soluble complexes upon interaction with oppositely charged linear
      polyelectrolytes. The phase behavior and molecular characteristics of the
      complexes were examined by turbidimetry, phase analysis, dynamic light
      scattering, and sedimentation velocity techniques. At an excess of
      polyelectrolyte micelles, soluble complexes were formed either independently on
      the route of preparation or, for select linear polyelectrolytes, through routes
      that avoided macrophase separation. Such soluble complexes are in a thermodynamic
      equilibrium state for all polyion pairs. The hydrodynamic sizes and sedimentation
      coefficients did not depend on the chemical nature of the linear polyelectrolyte,
      but were determined by the charge ratios and the hydrodynamic properties of the
      initial micelles. At an excess of linear polyelectrolyte, complex solubility and
      molecular characteristics depended on the chemical nature of the linear
      polyelectrolyte. In this region, linear polyelectrolytes formed soluble complexes
      with micelles if soluble complexes could be formed with the corresponding linear
      analogues of the block polyelectrolyte.

PMID- 17441752
TI  - Net charge and electrophoretic mobility of lysozyme charge ladders in solutions
      of nonionic surfactant.
AB  - We report on the electrophoretic mobility and on the thermal diffusion of
      lysozyme proteins dissolved in aqueous solutions of a nonionic surfactant (C12E6)
      at a wide range of concentrations of the surfactant (0-20% by weight). We want to
      estimate the influence of a dense network of elongated micelles of C12E6 on the
      effective charge of the proteins as observed in the capillary electrophoresis
      experiments. The possible mechanism leading to the change in the effective charge
      of protein could involve the deformation of the cloud of counterions around the
      protein when it squeezes through the narrow (of the order of a protein diameter)
      aqueous channels formed in the solution of elongated micelles. The combination of
      independent measurements of the electrophoretic mobility of a family of modified
      proteins (lysozyme charge ladder [Colton et al. J. Am. Chem. Soc. 1997, 119,
      12701]), of the microviscosity of the solutions of surfactant (obtained via
      fluorescence correlation spectroscopy), and of the hydrodynamic radius of the
      proteins (photon correlation spectroscopy) allow us to conclude that the
      effective charge of the proteins is not affected by the presence of surfactant,
      even at high concentrations.

PMID- 17441753
TI  - Circular differential scattering of light in films of chiral polyfluorene.
AB  - Circular differential transmission in thick films (1.1 mum) of poly{9,9-bis[(3S)
      3,7-dimethyloctyl]-2,7-fluorene} is investigated. The vitrified liquid
      crystalline film obtained after annealing shows high circular differential
      transmission of light in the wavelength range where the polyfluorene does not
      absorb (lambda > 450 nm). Using a specifically designed chiroptical setup, we
      show that circular selective reflection of light in which the circular
      polarization of the light is retained after reflection, a process which is
      characteristic for cholesteric liquid crystalline films, makes a negligible
      contribution to the differential transmission. Using an integrating sphere, we
      show that circular differential scattering can account for the observed circular
      differential transmission for lambda > 450 nm.

PMID- 17441754
TI  - Toward the computational design of diastereomeric resolving agents: an
      experimental and computational study of 1-phenylethylammonium-2-phenylacetate
      derivatives.
AB  - The crystal structures, including two new polymorphs, of three diastereomerically
      related salt pairs formed by (R)-1-phenylethylammonium (1) with (S&R)-2
      phenylpropanoate (2), (S&R)-2-phenylbutyrate (3), and (S&R)-mandelate (4) ions
      were characterized by low-temperature single crystal or powder X-ray diffraction.
      Thermal, solubility, and solution calorimetry measurements were used to determine
      the relative stabilities of the salt pairs and polymorphs. These were
      qualitatively predicted by lattice energy calculations combining realistic models
      for the dominant intermolecular electrostatic interactions and ab initio
      calculations for the ions' conformational energies due to the distortion of their
      geometries by the crystal packing forces. Crystal structure prediction studies
      were also performed for the highly polymorphic diastereomeric salt pair (R)-1
      phenylethylammonium-(S&R)-2-phenylbutyrate (1-3) in an attempt to predict the
      separation efficiency without relying on experimental information. This joint
      experimental and computational investigation provides a stringent test for the
      reliability of lattice modeling approaches to explain the origins of chiral
      resolution via diastereomer formation (Pasteurian resolution). The further
      developments required for the computational screening of single-enantiomer
      resolving agents to achieve optimal chiral separation are discussed.

PMID- 17441755
TI  - Mixed saturated-unsaturated alkyl-chain assemblies: solid solutions of zinc
      stearate and zinc oleate.
AB  - The linear saturated stearic acid and the bent mono-unsaturated oleic acid do not
      mix and form solid solutions. However, the zinc salts of these acids can. From X
      ray diffraction and DSC measurements we show that the layered zinc stearate and
      zinc oleate salts form a homogeneous solid solution at all composition ratios.
      The solid solutions exhibit a single melting endotherm, with the melting
      temperature varying linearly with composition but with the enthalpy change
      showing a minimum. By monitoring features in the infrared spectra that are
      characteristic of the global conformation of the hydrocarbon chain, and hence can
      distinguish between stearate and oleate chains, it is shown that solid solution
      formation is realized by the introduction of gauche defects in a fraction of the
      stearate chains that are then no longer linear. This fraction increases with
      oleate concentration. It has also been possible from the spectroscopic
      measurements to establish a quantitative relation between molecular
      conformational order and the thermodynamic enthalpy of melting of the solid
      solutions.

PMID- 17441756
TI  - Evolution of composition, molar mass, and conductivity during the free radical
      copolymerization of polyelectrolytes.
AB  - Despite their importance in biological and technological contexts, copolymeric
      polyelectrolytes (or "copolyelectrolytes") continue to present challenges to
      theorists and experimentalists. The first results of a unified approach to the
      kinetics and mechanisms of copolyelectrolyte synthesis and the physical
      characteristics of the resulting polymers are presented. The free radical
      copolymerization of 4-vinylbenzenesulfonic acid sodium salt and acrylamide was
      monitored using automatic continuous online monitoring of polymerization
      reactions (ACOMP), from which the average bivariate composition and mass
      distributions were determined. Composition drift was related to the evolution of
      conductivity. In some cases bimodal populations of copolyelectrolyte and
      homopolymeric poly(acrylamide) resulted, i.e., blends of copolyelectrolyte and
      neutral homopolymer. The end-product scattering behavior depended on whether the
      end-product was bimodal or not, as demonstrated using automatic continuous mixing
      (ACM) in conjunction with light scattering and viscosity. Negative light
      scattering third virial coefficients were found for bimodal end-products. This
      combined approach may allow connecting the synthesis kinetics to the resulting
      "trivariate" distribution of composition, molar mass, and linear charge density,
      which in turn controls the properties of end-product solutions, such as chain
      conformations, interparticle interactions, viscosity, interactions with colloids
      and other polymers, phase separation, etc. Unified results may allow testing and
      improvement of existing polyelectrolyte theories, development of new quantitative
      physicochemical models, provide advanced characterization methods, set the stage
      for studying more complex copolyelectrolytes, such as hydrophobically modified
      ones, and provide tools for ultimately controlling and tailoring the synthesis
      and properties of copolyelectrolytes.

PMID- 17441757
TI  - Origin of enhanced activity in palladium alloy electrocatalysts for oxygen
      reduction reaction.
AB  - We explored the origin of the enhanced activity of Pd-alloy electrocatalysts for
      the O2 reduction reaction by correlating the electrocatalytic activity of
      intrinsic Pd and Pt surfaces and Pd and Pt overlayers on several substrates with
      their electronic properties, and established the volcano-type dependence of O2
      reduction activity on the binding energy of oxygen and the d-band center of the
      top metal layer. Intrinsic Pd and Pt surfaces bind oxygen too firmly to allow
      efficient removal of the adsorbed reaction intermediates. Therefore, they do not
      have the highest activity and are not on the top of the volcano plot. A Pd
      overlayer on a Pd3Fe(111) alloy, was predicted to lie on top of the volcano plot,
      and thus, it appears to be the most active catalyst among investigated ones
      because of its moderate interaction with oxygen. The results can help in
      designing better electrocatalysts for fuel cells and other applications.

PMID- 17441758
TI  - Three-centers models for electron transfer through a bridge. 1. Potential energy
      surfaces.
AB  - Three centers models adapted to the description of electron transfer through a
      bridge are discussed, with a special emphasis on potential energy surfaces. A
      short historical review of the available models is given, with a particular
      interest on the Bersuker-Borshch-Chibotaru model (1989) and the Lambert-Noll
      Schelter model (2002). We propose our own model, inspired from the Bersuker
      Borshch-Chibotaru model, but with a more physical discussion of the parameters
      and coordinates. The diabatic surfaces, before the intervention of electronic
      couplings between external site and bridge, consist of three revolution
      paraboloids of equal radii. The bottoms of the paraboloids do not form in general
      an equilateral triangle; they form an isosceles one. At this stage, the basic
      parameters are the ones describing the position of the third paraboloid
      (corresponding to a redox process on the bridge) with respect to the other two.
      We define in particular an energy shift parameter (Delta) and a depth parameter
      (d), the latter corresponding to the position of this paraboloid in the third
      dimension, i.e., along a coordinate of reaction perpendicular to the usual
      reaction coordinate. The topology of diabatic and adiabatic surfaces is
      discussed. As an application, we explain the contrasted behavior of two mixed
      valence systems bridged by anthracene and dimethoxybenzodithiophene, which differ
      by the value of the d parameter.

PMID- 17441759
TI  - Critical factors for detection of biphasic changes in membrane properties at
      specific sterol mole fractions for maximal superlattice formation.
AB  - Here we use the excitation generalized polarization (GPex) of 6-lauroyl-2
      (dimethylamino)naphthalene (Laurdan) fluorescence in fluid cholesterol/1
      palmitoyl-2-oleoyl-l-alpha-phosphatidylcholine large unilamellar vesicles to
      explore the experimental conditions that would be required in order to detect a
      biphasic change in membrane properties at specific sterol mole fractions (Cr)
      (e.g., 20.0, 22.2, 25.0, 33.3, 40.0, and 50.0 mol %) for maximal sterol
      superlattice formation. Laurdan's GPex changes with sterol content in an
      alternating manner, showing minima (termed as GPex dips) at approximately Cr.
      GPex dips are detectable if the vesicles are preincubated for a sufficient time
      period and protected from sterol oxidation. In most cases, vesicles with a higher
      lipid concentration take a longer time to show a GPex dip at Cr. The depth of the
      GPex dip increases with increasing incubation time and eventually reaches a
      plateau, at which the maximum area covered by superlattices is expected to be
      achieved. However, if the vesicles are not protected against sterol oxidation,
      the GPex dips are attenuated or obliterated. These effects can be attributed to
      the increased inter-bilayer lipid exchange and the increased vesicle-vesicle
      interactions present at high lipid (vesicle) concentrations as well as the
      decreased interactions between oxysterols and phospholipids. These possible
      explanations have been incorporated into a kinetic model that is able to
      calculate the effects of sterol oxidation and lipid concentration on the depth of
      the GPex dip. The depth of the GPex dip, the required incubation time for the dip
      formation, and the lipid concentration dependence of the GPex dip vary with Cr,
      suggesting different physical properties for different sterol superlattices. To
      detect a biphasic change in membrane properties at Cr, one should also use small
      sterol mole fraction increments over a wide range, keep all of the vesicles in
      the same sample set under the same thermal history, and consider lipid
      concentration, probe type, and Cr value. These results improve our mechanistic
      understanding of sterol superlattice formation and explain why some studies,
      especially those requiring high lipid concentrations, did not detect a biphasic
      change in membrane properties at Cr.

PMID- 17441760
TI  - Time-domain calculations of the infrared and polarized Raman spectra of
      tetraalanine in aqueous solution.
AB  - The IR and polarized (isotropic and anisotropic) Raman spectra are calculated for
      the amide I band of tetraalanine ((Ala)4) in aqueous solution by using a time
      domain computational method, which includes the effects of the diagonal frequency
      modulations (of individual peptide groups), the off-diagonal (interpeptide)
      vibrational couplings, and structural dynamics. It is shown that the calculated
      band profiles, especially the existence of a large negative noncoincidence effect
      (i.e., large frequency separations between the IR, isotropic Raman, and
      anisotropic Raman bands, with the isotropic Raman being higher in frequency), are
      in reasonable agreement with the experimental results. This negative
      noncoincidence effect derives from two conditions: the positive coupling between
      the amide I vibrations of peptide groups and the angle larger than 90 degrees
      between the transition dipoles of the coupled vibrations. This result means that
      the dynamically changing structures mainly in the polyproline II and beta-type
      conformations containing some repeated interconversions obtained from the
      molecular dynamics calculation are consistent with the existence of a large
      negative noncoincidence effect, as far as the structures satisfy the above two
      conditions. It is also shown that the electric fields from solvent water
      molecules induce larger frequency shifts than those of intrachain interactions,
      with rapid underdamped oscillatory modulations ( approximately 43 fs) due to the
      librational motions of water molecules that give rise to motional narrowing
      effect on the spectra. The reason for the difference from the behavior seen for
      the O-H stretching mode of liquid water is discussed. The time-domain analysis of
      the mode identity shows that the system proceeds halfway to complete mode mixing
      with a similar time scale ( approximately 60 fs), suggesting the importance of
      the nonadiabatic effect, which is included in a natural way in the present
      computational method.

PMID- 17441761
TI  - Dynamics of water molecules in the active-site cavity of human cytochromes P450.
AB  - We have studied the dynamics of water molecules in six crystal structures of four
      human cytochromes P450, 2A6, 2C8, 2C9, and 3A4, with molecular dynamics
      simulations. In the crystal structures, only a few water molecules are seen and
      the reported sizes of the active-site cavity vary a lot. In the simulations, the
      cavities are completely filled with water molecules, although with approximately
      20% lower density than in bulk water. The 2A6 protein differs from the other
      three in that it has a very small cavity with only two water molecules and no
      exchange with the surroundings. The other three proteins have quite big cavities,
      with 41 water molecules on average in 2C8 and 54-58 in 2C9 and 3A4, giving a
      water volume of 1500-2100 A3. The two crystal structures of 2C9 differ quite
      appreciably, whereas those of 3A4 are quite similar. The active-site cavity is
      connected to the surroundings by three to six channels, through which there is a
      quite frequent exchange of water molecules (one molecule is exchanged every 30
      200 ps), except in 2A6. Most of the channels are observed also in the crystal
      structures, but two to three channels in each protein open only during the
      simulations. There are no water molecules close to the heme iron ion in these
      simulations of the high-spin ferric state (the average distance to the closest
      water molecule is 3.3-5 A), and there are few ordered water molecules in the
      active sites, none of which is conserved in all proteins.

PMID- 17441762
TI  - Ultrafast dynamics and excited state spectra of open-chain carotenoids at room
      and low temperatures.
AB  - Many of the spectroscopic features and photophysical properties of carotenoids
      are explained using a three-state model in which the strong visible absorption of
      the molecules is associated with an S0 (1(1)Ag-) --> S2 (1(1)Bu+) transition, and
      the lowest lying singlet state, S1 (2(1)Ag-), is a state into which absorption
      from the ground state is forbidden by symmetry. However, semiempirical and ab
      initio quantum calculations have suggested additional excited singlet states may
      lie either between or in the vicinity of S1 (2(1)Ag-) and S2 (1(1)Bu+), and some
      ultrafast spectroscopic studies have reported evidence for these states. One such
      state, denoted S*, has been implicated as an intermediate in the depopulation of
      S2 (1(1)Bu+) and as a pathway for the formation of carotenoid triplet states in
      light-harvesting complexes. In this work, we present the results of an ultrafast,
      time-resolved spectroscopic investigation of a series of open-chain carotenoids
      derived from photosynthetic bacteria and systematically increasing in their
      number of pi-electron carbon-carbon double bonds (n). The molecules are
      neurosporene (n = 9), spheroidene (n = 10), rhodopin glucoside (n = 11),
      rhodovibrin (n = 12), and spirilloxanthin (n = 13). The molecules were studied in
      acetone and CS2 solvents at room temperature. These experiments explore the
      effect of solvent polarity and polarizability on the spectroscopic and kinetic
      behavior of the molecules. The molecules were also studied in
      ether/isopentane/ethanol (EPA) glasses at 77 K, in which the spectral resolution
      is greatly enhanced. Analysis of the data using global fitting techniques has
      revealed the ultrafast dynamics of the excited states and spectral changes
      associated with their decay, including spectroscopic features not previously
      reported. The data are consistent with S* being identified with a twisted
      conformational structure, the yield of which is increased in molecules having
      longer pi-electron conjugations. In particular, for the longest molecule in the
      series, spirilloxanthin, the experiments and a detailed quantum computational
      analysis reveal the presence of two S* states associated with relaxed S1 (2(1)Ag
      ) conformations involving nearly planar 6-s-cis and 6-s-trans geometries. We
      propose that in polar solvents, the ground state of spirilloxanthin takes on a
      corkscrew conformation that generates a net solute dipole moment while decreasing
      the cavity formation energy. Upon excitation and relaxation into the S1 (2(1)Ag-)
      state, the polyene unravels and flattens into a more planar geometry with
      comparable populations of 6-s-trans and 6-s-cis conformations.

PMID- 17441763
TI  - Charge transfer absorption for pi-conjugated polymers and oligomers mixed with
      electron acceptors.
AB  - Pi-conjugated polymers and oligomers show charge transfer (CT) absorption bands
      when mixed with electron acceptors in chloroform solution. This is attributed to
      the formation of (ground state) donor-acceptor complexes in solution. By varying
      the concentration of the donor and acceptor, the extinction coefficient for the
      CT absorption and the association constant of donor and acceptor are estimated.
      The spectral position of the CT bands correlates with the electrochemical
      oxidation potential of the pi-conjugated donor and the reduction potential of the
      acceptor.

PMID- 17441764
TI  - Enhanced mechanical stability of microtubules polymerized with a slowly
      hydrolyzable nucleotide analogue.
AB  - Atomic force microscopy (AFM) has been used to investigate the local mechanical
      and structural properties of microtubules polymerized using guanylyl-alpha-beta
      methylene diphosphonate (GMPCPP), a slowly hydrolyzable analogue of guanosine
      triphosphate. Using a combination of AFM imaging and local force spectroscopy,
      GMPCPP-polymerized microtubules have been qualitatively and quantitatively
      compared to paclitaxel-stabilized microtubules. GMPCPP-polymerized microtubules
      qualitatively display a greater resistance to destruction by the AFM probe tip
      during imaging and during deformation measurements and maintain structural
      details after indentation. In addition, using force spectroscopy taken during the
      indentation and collapse of individual microtubules with the AFM probe tip, an
      effective spring constant of the microtubule wall (kMT) for both types of
      microtubules was determined. The average kMT of GMPCPP-polymerized microtubules,
      0.172 N/m, is more than twice that of paclitaxel-stabilized microtubules. These
      results complement previously reported measurements of bending experiments on
      GMPCPP-polymerized and paclitaxel-stabilized microtubules.

PMID- 17441765
TI  - SO2 gas separation using supported ionic liquid membranes.
AB  - Measurements of permeability of sulfur dioxide (SO2) in five imidazolium-based
      ionic liquids supported on the polyethersulfone microfiltration membranes at
      temperatures from 25 to 45 degrees C and atmospheric pressure indicate that under
      the same conditions, the SO2 selectivity of separations using supported ionic
      liquid membranes are 9-19 times that of CO2.

PMID- 17441766
TI  - Nuclear magnetic resonance study of the dynamics of imidazolium ionic liquids
      with -CH2Si(CH3)3 vs -CH2C(CH3)3 substituents.
AB  - Trimethylsilylmethyl (TMSiM)-substituted imidazolium
      bis(trifluoromethylsulfonyl)imide (NTf(2)-), and tetrafluoroborate (BF(4)-) ionic
      liquids (ILs) have lower room-temperature viscosities by factors of 1.6 and 7.4,
      respectively, than isostructural neopentylimidazolium ILs. In an attempt to
      account for the effects of silicon substitution in imidazolium RTILs and to
      investigate the ion dynamics, we report nuclear magnetic resonance (NMR)
      measurements of 1H (I = 1/2) and 19F (I = 1/2) spin-lattice relaxation times (T1)
      and self-diffusion coefficients (D) as a function of temperature for ILs
      containing the TMSiM group and, for comparison, the analogous neopentyl group.
      The 1H and 19F nuclei probe the dynamics of the cations and anions, respectively.
      The low-temperature line shapes were determined to be Gaussian, and the onset of
      the rigid lattice line width is correlated with the measured glass transition
      temperature. The spin-lattice relaxation data feature a broad T1 minimum as a
      function of inverse temperature for both nuclear species. The Arrhenius plots of
      the diffusion data for both nuclear species are found to exhibit Vogel-Tammann
      Fulcher curvature. Analysis of the eta and D data generally show fractional
      Stokes-Einstein behavior D proportional to (T/eta)m. This is most prominent in
      the neopentylimidazolium BF(4)- IL with m approximately 0.66.

PMID- 17441767
TI  - Probe diffusion in aqueous poly(vinyl alcohol) solutions studied by fluorescence
      correlation spectroscopy.
AB  - We report fluorescence correlation spectroscopy measurements of the translational
      diffusion coefficient of various probe particles in dilute and semidilute aqueous
      poly(vinyl alcohol) solutions. The range of sizes of the particles (fluorescent
      molecules, proteins, and polymers) was chosen to explore various length scales of
      the polymer solutions as defined by the polymer-polymer correlation length. For
      particles larger than the correlation length, we find that the diffusion
      coefficient, D, decreases exponentially with the polymer concentration. This can
      be explained by an exponential increase in the solution viscosity, consistent
      with the Stokes-Einstein equation. For probes on the order of the correlation
      length, the decrease of the diffusion coefficient cannot be accounted for by the
      Stokes-Einstein equation, but can be fit by a stretched exponential, D
      approximately exp(-alphacn), where we find n = 0.73-0.84 and alpha is related to
      the probe size. These results are in accord with a diffusion model of Langevin
      and Rondelez (Polymer 1978, 19, 1875), where these values of n indicate a good
      solvent quality.

PMID- 17441768
TI  - Diffusion and conformation of peptide-functionalized polyphenylene dendrimers
      studied by fluorescence correlation and 13C NMR spectroscopy.
AB  - We report on the combined use of fluorescence correlation spectroscopy (FCS) and
      1H and 13C NMR spectroscopy to detect the size and type of peptide secondary
      structures in a series of poly-Z-L-lysine functionalized polyphenylene dendrimers
      bearing the fluorescent perylenediimide core in solution. In dilute solution, the
      size of the molecule as detected from FCS and 1H NMR diffusion measurements
      matches nicely. We show that FCS is a sensitive probe of the core size as well as
      of the change in the peptide secondary structure. However, FCS is less sensitive
      to functionality. A change in the peptide secondary conformation from beta-sheets
      to alpha-helices detected by 13C NMR spectroscopy gives rise to a steep increase
      in the hydrodynamic radii for number of residues n > or = 16. Nevertheless,
      helices are objects of low persistence.

PMID- 17441769
TI  - Antimalarial linear lipopeptides from a Panamanian strain of the marine
      cyanobacterium Lyngbya majuscula.
AB  - As part of the Panama International Cooperative Biodiversity Groups (ICBG)
      project, two new (2, 4) and two known (1, 3) linear alkynoic lipopeptides have
      been isolated from a Panamanian strain of the marine cyanobacterium Lyngbya
      majuscula. Carmabin A (1), dragomabin (2), and dragonamide A (3) showed good
      antimalarial activity (IC50 4.3, 6.0, and 7.7 microM, respectively), whereas the
      nonaromatic analogue, dragonamide B (4), was inactive. The planar structures of
      all four compounds were determined by NMR spectroscopy in combination with mass
      spectrometry, and their stereoconfigurations were established by chiral HPLC and
      by comparison of their optical rotations and NMR data with literature values.

PMID- 17441770
TI  - Synthesis, spectroscopic, electrochemical and Pb2+-binding studies of
      tetrathiafulvalene acetylene derivatives.
AB  - A series of tetrathiafulvalene acetylene derivatives, [TTF-Ctriple bondC-A]
      [A=C6H4N(CH3)2-4 (1), C6H4OCH3-4 (2), C6H5 (3), C6H4F-4 (4), C6H4NO2-4 (5), C5H4N
      2 (6), C5H4N-3 (7), and C5H4N-4 (8)], have been designed and synthesized to
      provide insight into the nature of the donor-acceptor interaction via a pi
      conjugated triple bond. The X-ray crystal structure of [TTF-(Ctriple bondC)
      C6H4OCH3-4] (2) reveals that the phenyl ring linked by acetylene is almost
      coplanar to the plane of TTF with a dihedral angle of 3.6 degrees. The strong
      intermolecular C-H...O hydrogen bonding was found to direct the molecular helical
      assemblies with a screw pitch of 5.148 A when viewed along the a-axis.
      Spectroscopic and electrochemical behaviors of the tetrathiafulvalene acetylene
      derivatives demonstrate that the TTF unit interacts with the electron-accepting
      group through the triple bond, thus leading to the intramolecular charge
      transfer. The pyridine-substituted TTF compounds 6-8 show remarkable sensing and
      coordinating properties toward Pb2+. Comparison of the spectroscopic and
      electrochemical properties and the calculation at the B3LYP/6-31G* level
      available in Gaussian 03 reveals that varying the bridged unit of the TTF-pi-A
      system from a double bond to a triple bond leads to positive shifts for the first
      and second oxidation potentials of the TTF moieties, while the extent of
      intramolecular charge transfer interactions through the pi-conjugated triple bond
      is smaller than that through the double bond.

PMID- 17441771
TI  - First total synthesis and assignment of the stereochemistry of crispatenine.
AB  - The first racemic and enantioselective synthesis of crispatenine 1 has been
      achieved, which involved a few steps, enabling the assignment of the absolute and
      relative configurations.

PMID- 17441773
TI  - 2beta-(N-substituted piperazino)-5alpha-androstane-3alpha,17beta-diols: parallel
      solid-phase synthesis and antiproliferative activity on human leukemia HL-60
      cells.
AB  - Leukemia is the most common cancer affecting children. A steroid possessing a
      methylpiperazine nucleus was recently reported to inhibit the proliferation of HL
      60 leukemia cells. To speed up the development of this promising potential new
      drug, we generated libraries of analogues using parallel solid-phase organic
      synthesis (SPOS). A 6-step sequence of reactions, starting from
      dihydrotestosterone, afforded a steroidal 2,3alpha-epoxide, which was selectively
      opened to give, after N-Fmoc protection, a diol with suitable stereochemistry.
      The difference of reactivity between 3alpha-OH and 17beta-OH was then used to
      allow the regioselective coupling of 17beta-OH to chloro-activated
      butyldiethylsilane polystyrene. We next generated three libraries of 2beta
      piperazinyl-5alpha-androstane-3alpha,17beta-diol N-derivatives with 1, 2, or 3
      levels of molecular diversity in acceptable yields and purities for our
      biological screening assay. Several members of these libraries were more potent
      than the lead compound, especially five members with a proline as the first level
      of diversity and a cyclohexylcarbonyl, methylbutyryl, cyclohexylacetyl,
      cyclopentylpropionyl, or hexanoyl as the second level of diversity. They
      efficiently inhibited HL-60 cell proliferation with IC50 values of 0.58, 0.66,
      1.78, 1.98, and 2.57 microM, respectively. The present work demonstrates the
      potential of our SPOS approach for the optimization of a new class of cytotoxic
      agents.

PMID- 17441774
TI  - Electron dephasing and weak localization in Sn doped In(2)O(3) nanowires.
AB  - We report on (magneto-) transport measurements of individual In2O3 nanowires. We
      observed that the presence of a weak disorder arising from doping and electron
      boundary collisions leads to weak localization of electrons as revealed by the
      positive magnetoconductivity in a large range of temperatures ( approximately 77
      K). From temperature-dependent resistance and magnetoconductivity data, the
      electron-electron interaction was pointed out as the mechanism responsible for
      the increase of resistance in the low temperature range and the dominant source
      of the dephasing at low temperatures. The experimental data provided the phase
      coherence time tau(phi) approximately T(-2/3) expected for 1D systems, giving
      consistent support to the mechanisms underlying the weak-localization and
      electron-electron scattering theories.

PMID- 17441778
TI  - Editorial: the critical role of behavioral research for improving adherence to
      continuous positive airway pressure therapies for sleep apnea.

PMID- 17441779
TI  - Workshop report: effects of sleep disorders and sleep restriction on adherence to
      cardiovascular and other disease treatment regimens: research needs.

PMID- 17441780
TI  - Brief behavioral therapies reduce early positive airway pressure discontinuation
      rates in sleep apnea syndrome: preliminary findings.
AB  - Sleep apnea syndrome (SAS) is a serious disorder with significant daytime
      consequences. Treatment for SAS most commonly takes the form of positive airway
      pressure (PAP). Although effective, PAP adherence is often below expectations.
      Previous studies have suggested that the provision of information on the
      importance of PAP use can enhance adherence. In this study, we compare 2 brief
      behavioral approaches-traditional education (ED) and a motivational enhancement
      therapy (MET)-designed from theories of behavior change to standard clinical
      care. PAP discontinuation and adherence are the primary outcome measures. Both
      brief therapies decreased PAP discontinuation compared to standard care. The MET
      therapy performed best under the condition of flexible delivery of PAP, although
      differences were not statistically significant. Implications are discussed.

PMID- 17441781
TI  - Graded exposure therapy for addressing claustrophobic reactions to continuous
      positive airway pressure: a case series report.
AB  - Continuous positive airway pressure (CPAP) is a safe, effective treatment for
      obstructive sleep apnea, and yet many patients develop claustrophobic reactions
      to the CPAP nasal mask and cannot tolerate this treatment. We examined the
      efficacy of a graded in-vivo exposure therapy for enhancing CPAP adherence using
      a retrospective, case series design. Objective CPAP adherence data were obtained
      on clinical patients who attended 1 or more sessions of exposure therapy with a
      behavioral sleep psychologist. Compared to pre-treatment, patients used CPAP
      significantly longer after exposure therapy. No predictors of treatment response
      were identified. CPAP exposure therapy may be beneficial in some cases; however,
      further research is needed to determine types of patients most likely to benefit
      from this therapy.

PMID- 17441782
TI  - The effect of one versus two nights of in-laboratory continuous positive airway
      pressure titration on continuous positive airway pressure compliance.
AB  - OBJECTIVE: To investigate continuous positive airway pressure (CPAP) compliance
      after one versus two nights of CPAP titration. METHOD: A chart review and a
      telephone questionnaire interview were conducted in 110 sleep apnea patients who
      received one or two nights of CPAP titration. Of these patients, 78 followed
      through with phone interview. RESULTS: There was no difference in CPAP compliance
      between those who had one or two nights of CPAP titration. The titration
      pressures on the first and second nights were not significantly different. But
      there was significant improvement in sleep efficiency from the first to the
      second diagnostic night. CONCLUSION: One versus two nights of CPAP titration did
      not affect CPAP compliance, but sleep efficiency improved on the second
      diagnostic night and an extra titration study may be necessary for some patients,
      especially those with only one diagnostic night.

PMID- 17441783
TI  - A self-management approach to improving continuous positive airway pressure
      adherence and outcomes.
AB  - Obstructive sleep apnea (OSA) is a condition with serious medical and
      psychosocial consequences. Low patient adherence to nasal continuous positive
      airway pressure (CPAP) limits the effectiveness of treatment. Intervention
      studies based on intensive support protocols have shown modest improvement in
      CPAP adherence; however, this approach would require significant resources and
      effort for integration into the existing U.S. health care system. The purpose of
      this article is to describe the self-management approach to chronic illness,
      justify the self-management approach as applied to sleep apnea patients
      prescribed CPAP, and to report initial pilot data on feasibility and efficacy of
      the Sleep Apnea Self-Management Program. CPAP adherence measured at the end of
      the 4-session program averaged 5.5 +/- 2.3 hr per night. The Sleep Apnea Self
      Management Program (SASMP) has the potential to be an effective and practical way
      to improve CPAP adherence and is designed for integration into current OSA
      clinical processes.

PMID- 17441784
TI  - Behavioral training for increasing preschool children's adherence with positive
      airway pressure: a preliminary study.
AB  - Behavioral training was implemented to increase adherence with positive airway
      pressure (PAP) in 4 preschool children. The training employed distraction,
      counterconditioning, graduated exposure, differential reinforcement, and escape
      extinction. A non-concurrent multiple baseline experimental design was used to
      demonstrate program effects. Initially, the children displayed distress and
      escape-avoidance behavior when PAP was attempted. With training, all 4 children
      tolerated PAP while sleeping for age appropriate durations. For the 3 children
      with home follow-up data, the parents maintained benefits. The results are
      discussed in relation to behavior principles, child health, and common barriers
      to PAP adherence.

PMID- 17441785
TI  - 40 years with bacteriophage o29.
AB  - I have dedicated the past 46 years of my life to science and I expect to be
      active in research for many more years. I have been lucky in my professional
      life. During my postdoctoral years I discovered two proteins that I showed to be
      involved in the initiation of protein synthesis. Working with bacteriophage o29
      for the past 40 years, we have made many interesting findings. Among them is the
      discovery of a protein covalently linked to the 5' ends of o29 DNA that we later
      showed to be the primer for the initiation of o29 DNA replication. Also, the
      finding of the o29 DNA polymerase with its properties of high processivity,
      strand displacement, and high fidelity has been very rewarding. The o29 DNA
      polymerase has become the ideal enzyme for DNA amplification, both rolling circle
      and whole-genome amplification. I also am happy because I have worked with many
      brilliant students and collaborators over the years, most of whom have become
      excellent scientists.

PMID- 17441786
TI  - Phosphorylation of the Aspergillus oryzae Woronin body protein, AoHex1, by
      protein kinase C: evidence for its role in the multimerization and proper
      localization of the Woronin body protein.
AB  - Woronin body, a specialized peroxisome, is a unique organelle involved in septal
      pore sealing and protecting filamentous fungus from excessive cytoplasmic
      bleeding. We recently characterized the Aohex1 gene encoding the major protein of
      the Woronin body in the fungus Aspergillus oryzae. Although three-dimensional
      microscopy revealed plugging of the septal pore by Woronin body, the mechanism of
      its formation remains unknown. We report here a reduction in the oligomeric forms
      (dimeric and tetrameric) of AoHex1 upon l-phosphatase treatment, which indicated
      that AoHex1 phosphorylation in vivo facilitates its oligomerization. Concomitant
      with the presence of a highly conserved predicted PKC (protein kinase C)
      phosphorylatable site (Ser151), the recombinant AoHex1 was phosphorylated by PKC
      in vitro and the administration of the PKC inhibitors, bisindolylmaleimide I and
      chelerythrine, resulted in the reduction of the oligomeric forms of AoHex1 in
      vivo. While spherical dot-like Woronin bodies were visualized by expressing the
      dsred2-Aohex1 and egfp (enhanced green fluorescent protein)-Aohex1 constructs in
      A. oryzae, treatment with the PKC inhibitors caused an abnormal localization to
      ring-like structures. In addition to the reduced phosphorylation of the
      mutagenized recombinant AoHex1[S151A] (Ser151 to alanine substitution) by PKC in
      vitro, the overexpression of Aohex1[S151A] as dsred2 fusion against the wild-type
      background also showed reduction of the oligomeric forms of the endogenous AoHex1
      and its perturbed localization to ring-like structures in vivo. In conclusion,
      the present study implicates the relevance of PKC-dependent phosphorylation of
      the Woronin body protein, AoHex1, for its multimerization and proper
      localization.

PMID- 17441788
TI  - Anaphylaxis during anaesthesia: diagnostic approach.
AB  - Correct management of anaphylaxis during anaesthesia requires a multidisciplinary
      approach with prompt recognition and treatment of the acute event by the
      attending anaesthesiologist, and subsequent determination of the responsible
      agent(s) with strict avoidance of subsequent administration of all incriminated
      and/or cross-reacting compounds. However, correct identification of the causative
      compound(s) and safe alternatives is not always straightforward and, too often,
      not done. This review is not intended to discuss acute management of anaesthesia
      related anaphylaxis but summarizes the major causes of anaphylaxis during
      anaesthesia and the diagnostic approach of this rare but potentially life
      threatening complication. Apart from general principles about the diagnostic
      approach, history taking and importance of tryptase quantification, more specific
      confirmatory diagnostic procedures are organized on the basis of the major causes
      of perioperative anaphylactic reactions.

PMID- 17441787
TI  - Relative sensitivity of soluble guanylate cyclase and mitochondrial respiration
      to endogenous nitric oxide at physiological oxygen concentration.
AB  - Nitric oxide (NO) is a widespread biological messenger that has many
      physiological and pathophysiological roles. Most of the physiological actions of
      NO are mediated through the activation of sGC (soluble guanylate cyclase) and the
      subsequent production of cGMP. NO also binds to the binuclear centre of COX
      (cytochrome c oxidase) and inhibits mitochondrial respiration in competition with
      oxygen and in a reversible manner. Although sGC is more sensitive to endogenous
      NO than COX at atmospheric oxygen tension, the more relevant question is which
      enzyme is more sensitive at physiological oxygen concentration. Using a system in
      which NO is generated inside the cells in a finely controlled manner, we
      determined cGMP accumulation by immunoassay and mitochondrial oxygen consumption
      by high-resolution respirometry at 30 microM oxygen. In the present paper, we
      report that the NO EC50 of sGC was approx. 2.9 nM, whereas that required to
      achieve IC50 of respiration was 141 nM (the basal oxygen consumption in the
      absence of NO was 14+/-0.8 pmol of O2/s per 10(6) cells). In accordance with
      this, the NO-cGMP signalling transduction pathway was activated at lower NO
      concentrations than the AMPKs (AMP-activated protein kinase) pathway. We conclude
      that sGC is approx. 50-fold more sensitive than cellular respiration to
      endogenous NO under our experimental conditions. The implications of these
      results for cell physiology are discussed.

PMID- 17441789
TI  - Early and late phase asthmatic response in lower airways of cat-allergic
      asthmatic patients--a comparison between experimental and environmental allergen
      challenge.
AB  - BACKGROUND: Standardized experimental allergen challenges are usually adopted to
      investigate the effect of allergen exposure on the lower airways. Environmental
      (natural) allergen challenges are used less often, mainly because of difficulties
      in standardizing the method, safety reasons and costs. The aim of this study was
      to investigate the relationship between an experimental and an environmental
      bronchial challenge. For this reason a natural challenge model was developed.
      METHODS: Sixty-two patients with a history of cat allergen-induced symptoms
      involving the lower airways, positive skin prick test, positive in vitro specific
      IgE to cat allergen and bronchial hyper-responsiveness were included. All 62
      patients underwent an experimental challenge in the laboratory followed by an
      environmental allergen challenge. RESULTS: All 62 patients developed an early
      asthmatic response [>or=20% fall in forced expiratory volume in 1 s (FEV1)] in
      the experimental challenge and 60% (37/62) during the environmental challenge. A
      late asthmatic response (>or=15% fall in FEV1 within 3-24 h) was seen in 56%
      (35/62) of the patients after the experimental challenge. Following the
      environmental challenge 47% (29/62) of the patients developed a late response.
      Thirty-four per cent (21/62) of the patients developed a late response in both
      challenge models and 31% (19/62) did not develop a late response in any model.
      Thus, there was consistency in 65% (40/62) of the patients in both challenge
      models. CONCLUSION: We found consistency in the pattern of response to inhaled
      allergen between the two challenge models and we believe that experimental
      bronchial challenge is likely to reflect the development of relevant inflammation
      in the lower airways after low-dose allergen exposure in the environment.

PMID- 17441790
TI  - Airway expression of calcitonin gene-related peptide in T-cell peptide-induced
      late asthmatic reactions in atopics.
AB  - BACKGROUND: The mechanisms of late asthmatic reactions provoked in atopic
      asthmatics by allergen-derived T-cell peptide epitopes remain unclear. Previous
      studies showed no changes in airway eosinophils or mast cell products after
      peptide challenge. In the present study our aim was to measure calcitonin gene
      related peptide (CGRP), neurokinin (NK)-A, and substance P (SP) in
      bronchoalveolar lavage fluid and bronchial biopsies (BB) after inhalation of
      allergen-derived T-cell peptide epitopes since these neuropeptides (NP) had not
      previously been evaluated in this chronic asthma model. METHODS: Bronchoscopy,
      with BB and bronchoalveolar lavage (BAL), was performed in 24 cat-allergic
      subjects 6 h after inhalation of Fel d 1-derived peptides. Neuropeptides were
      measured in BAL by enzyme-linked immunosorbent assay and CGRP expression in the
      airways was assessed by immunohistochemistry and confocal microscopy. RESULTS:
      Twelve subjects (termed 'responders') developed isolated late reactions.
      Calcitonin gene-related peptide, but not NK-A or SP, was significantly elevated
      in BAL in responders only. Biopsy studies showed that in virtually all responders
      peptide challenge induced marked increases in CGRP immunoreactivity in bronchial
      epithelial cells, infiltrating submucosal cells and in association with airway
      smooth muscle. Double immunostaining indicated that CGRP colocalized
      predominantly to CD3+/CD4+ and CD68+ submucosal inflammatory cells. CONCLUSION:
      Calcitonin gene-related peptide, a potent vasodilator, is markedly up-regulated
      in the airways of atopic asthmatics during late-phase reactions provoked by
      inhalation of allergen-derived T-cell peptides.

PMID- 17441791
TI  - House dust (1-3)-beta-D-glucan and wheezing in infants.
AB  - BACKGROUND: (1-3)-Beta-D-glucan is a fungal cell wall component, suspected to
      cause respiratory symptoms in adults. However, very little is known on the
      possible health effects of (1-3)-beta-D-glucan during infancy. We examined the
      association between (1-3)-beta-D-glucan exposure and the prevalence of allergen
      sensitization and wheezing during the first year of life in a birth cohort of 574
      infants born to atopic parents. Endotoxin exposure was included as a possible
      confounder. METHODS: (1-3)-Beta-D-glucan and endotoxin exposures were measured in
      settled dust collected from infants' primary activity rooms. The primary outcomes
      at approximately age one included parental reports of recurrent wheezing and
      allergen sensitization evaluated by skin prick testing to a panel of 15
      aeroallergens as well as milk and egg white. RESULTS: Exposure to high (1-3)-beta
      D-glucan concentration (within fourth quartile) was associated with reduced
      likelihood of both recurrent wheezing [adjusted OR (aOR) = 0.39, 95% CI = 0.16
      0.93] and recurrent wheezing combined with allergen sensitization (aOR = 0.13,
      95% CI = 0.03-0.61). Similar trends were found between (1-3)-beta-D-glucan
      concentrations and allergen sensitization (aOR = 0.57, 95% CI = 0.30-1.10). In
      contrast, recurrent wheezing with or without allergen sensitization was
      positively associated with low (1-3)-beta-D-glucan exposure within the first
      quartile (aOR = 3.04, 95% CI = 1.25-7.38; aOR = 4.89, 95% CI = 1.02-23.57). There
      were no significant associations between endotoxin exposure and the studied
      health outcomes. CONCLUSIONS: This is the first study to report that indoor
      exposure to high levels of (1-3)-beta-D-glucan (concentration >60 microg/g) is
      associated with decreased risk for recurrent wheezing among infants born to
      atopic parents. This effect was more pronounced in the subgroup of allergen
      sensitized infants.

PMID- 17441792
TI  - A nonsynonymous substitution of cystatin A, a cysteine protease inhibitor of
      house dust mite protease, leads to decreased mRNA stability and shows a
      significant association with atopic dermatitis.
AB  - BACKGROUND: Cystatin A (CSTA) is a strong candidate for atopic dermatitis (AD)
      because it maps to AD susceptibility locus on chromosome 3q21 and it does inhibit
      Der p 1 and Der f 1, major house dust mite cysteine proteases and environmental
      triggers for AD and asthma. OBJECTIVE: To examine any association between
      polymorphisms in CSTA and AD and study the effect on the CSTA mRNA expression
      level. METHODS: We identified three polymorphisms and characterized the linkage
      disequilibrium mapping of the CSTA gene. All three CSTA polymorphisms were
      genotyped in 100 AD patients and 203 matched controls. Subsequently, we performed
      transfection-based RNA stability assays. RESULTS: We found a significant
      association between the CSTA +344C variant and AD [odds ratio (OR) = 1.91; P =
      0.024]. When further 61 control samples were genotyped. The association with CSTA
      +344C allele was enhanced OR = 2.13; P = 0.006. To test whether the CSTA +344
      affected the CSTA transcriptional activity, the decay rates of RNAs transcribed
      from the CSTA +344C and CSTA +344T variants were investigated. COS-7 cells were
      transfected with a pcDNA3.1-CSTA+344C or a pcDNA3.1-CSTA+344T construct and
      cultured in the presence or absence of actinomycin D. Real-time RT-PCR revealed
      that CSTA +344C mRNA is more than two times less stable than the CSTA +344T mRNA
      (P < 0.001). CONCLUSION: These results suggest that the CSTA +344C allele
      associated with unstable mRNA could result in failing to protect the skin barrier
      in AD patients from both exogenous and endogenous proteases.

PMID- 17441793
TI  - Codeine induces human mast cell chemokine and cytokine production: involvement of
      G-protein activation.
AB  - BACKGROUND: Activation of mast cells and the systemic release of histamine are
      common side effects of opiates such as codeine and morphine. In some individuals,
      codeine not only elicits a sizable early response due to mast cell degranulation,
      but can also lead to late cutaneous allergic inflammation possibly through the
      production of chemokines. However, individuals who exhibit a late phase reaction
      to codeine often do not react to its synthetic analog, meperidine. The goal of
      this study was to test whether codeine and meperidine induce secretion of
      inflammatory mediators in human mast cells. METHODS: To characterize opiate
      activation of human mast cells, we stimulated cultured human (LAD2 cell line and
      CD34+-derived) mast cells with codeine and meperidine and measured degranulation
      and chemokine production. RESULTS: Codeine, but not meperidine, activated human
      mast cell degranulation within 30 min in a dose-dependent manner. Degranulation
      was blocked by the phosphoinositol-3 kinase (PI3K) inhibitor, wortmannin, and
      pertussis toxin but not by Ro-31-8220, a PKC inhibitor or forskolin, a cyclic
      adenylyl cyclase activator. After 3 and 8 h of stimulation, codeine, but not
      meperidine, activated human mast cells to release monocyte chemoattractant
      protein-1 (CCL2), regulated on activation, normal T expressed and secreted
      (RANTES, CCL5) and interleukin-8 (CXCL 8) but not inducible protein-10 (CXCL10).
      CONCLUSIONS: Codeine activates human mast cell degranulation and chemokine
      production by activating protein kinase A and PI3 kinase, possibly leading to NF
      kappaB activation. Therefore, opiates may regulate late phase allergic
      inflammation by activating chemokine production by human mast cells.

PMID- 17441794
TI  - Rupatadine in the treatment of chronic idiopathic urticaria: a double-blind,
      randomized, placebo-controlled multicentre study.
AB  - BACKGROUND: Chronic urticaria is one of the most common and disturbing cutaneous
      condition. The treatment of chronic idiopathic urticaria (CIU) is still a
      challenge. Antihistamines are recommended as first-line treatment. Rupatadine is
      a new potent nonsedative anti-H1. OBJECTIVE: To study rupatadine efficacy and
      safety for moderate to severe CIU treatment. METHODS: This randomized, double
      blind, placebo-controlled, parallel-group, multicentre, study was designed to
      assess primarily mean pruritus score (MPS) reduction with rupatadine, 10 and 20
      mg, administered once daily for 4 weeks. Three hundred and thirty-three patients
      with active episodes of moderate-to-severe CIU were included. RESULTS: A 57.5% (P
      < 0.005) and 63.3% (P = 0.0001) significative MPS reduction from baseline, was
      observed at week 4 with 10 and 20 mg rupatadine, respectively, compared with
      placebo (44.9%). Both doses of rupatadine were not significantly different at any
      time point, with respect to their effects on pruritus severity, number of wheals
      and total symptoms scores. Rupatadine 10 mg had an overall better adverse event
      profile. CONCLUSION: Rupatadine 10 mg is a fast, long-acting, efficacious and
      safe treatment option for the management of patients with moderate-to-severe CIU.

PMID- 17441796
TI  - Psychosocial factors and incident asthma hospital admissions in the EPIC-Norfolk
      cohort study.
AB  - BACKGROUND: Case series and case-control studies have shown high rates of
      psychosocial and behavioural risk factors amongst patients admitted to hospital
      with severe asthma. General population studies have shown associations between
      psychosocial factors and prevalent asthma but few have investigated incident
      asthma outcomes. METHODS: Data on psychosocial factors and asthma hospital
      admissions were available for 20 854 participants, aged 41-80 years, in the
      Norfolk cohort of the European Prospective Investigation into Cancer study.
      Postal assessments included details of physical functioning, mood disorder
      history, social adversity and social support. RESULTS: A total of 686 asthma
      hospital admissions were recorded. Psychosocial factors present at baseline,
      including current mood disorders, adverse circumstances in childhood, the impact
      of life events experienced during adulthood and negative perceived support from a
      close confidant, were associated with increased rates of hospital admission
      independent of age, sex, indicators of socio-economic status, physical functional
      health, and obesity. Restricted to those participants who reported lifetime
      doctor-diagnosed asthma at baseline, the reported impact of adverse life events
      experienced in adulthood, and both confiding and negative aspects of support
      quality, were associated with asthma hospital admission. The magnitude of these
      associations was comparable to those involving indicators of socio-economic
      status and physical health. CONCLUSIONS: These results show that psychosocial
      factors are associated with incident asthma hospital admissions and highlight the
      potential importance of taking account of psychosocial factors, including
      availability and quality of support networks, in guiding long-term asthma
      management.

PMID- 17441795
TI  - Isolation and characterization of native Cry j 3 from Japanese cedar (Cryptomeria
      japonica) pollen.
AB  - BACKGROUND: Japanese cedar (Cryptomeria japonica) pollinosis is the most
      prevalent allergy in Japan. Recently, the Japanese cedar pollen allergen Cry j 3
      was cloned as a homologue of Jun a 3, which is a major allergen from mountain
      cedar (Juniperus ashei) pollen. However, native Cry j 3 has not been isolated and
      there are no reports on its allergenic activity. The aims of this study were to
      isolate native Cry j 3 and assess its immunoglobulin E (IgE)-binding capacity in
      patients with Japanese cedar pollinosis. METHODS: Native Cry j 3 was purified
      from Japanese cedar pollen by multidimensional chromatography. We assessed the
      IgE-binding capacity using sera from patients allergic to Japanese cedar pollen
      by immunoblot analysis and ELISA. Moreover, we assayed the capacity of Cry j 3 to
      induce histamine release from the patients' leukocytes. We cloned cDNA
      corresponding to purified Cry j 3 from a cDNA library of Japanese cedar pollen.
      RESULTS: We isolated native Cry j 3 as a 27-kDa protein. The IgE-binding
      frequency of Cry j 3 from the sera of patients allergic to Japanese cedar pollen
      was estimated as 27% (27/100) by ELISA. Cry j 3 induced the release of histamine
      from leukocytes. We cloned the cDNA and named it Cry j 3.8. Cry j 3.8 cDNA
      encoded 225 amino acids and had significant homology with thaumatin-like
      proteins. CONCLUSIONS: Cry j 3 is a causative allergen in Japanese cedar
      pollinosis and may play crucial roles in the cross-reactivity with oral allergy
      syndrome.

PMID- 17441797
TI  - Evaluation of the IgE cross-reactions among vespid venoms. A possible approach
      for the choice of immunotherapy.
AB  - BACKGROUND: Hymenoptera venom allergy can be effectively cured with specific
      immunotherapy, thus the correct identification of the allergen is essential. In
      the case of multiple skin and serum positivities it is important to know if a
      cross-reaction among venoms is present. We studied by CAP-inhibition assays the
      degree of cross-reactivity between Vespula vulgaris and Polistes dominulus.
      METHODS: Serum samples were obtained from consecutive patients with a clinical
      history of grade III-IV reactions to hymenoptera sting and with nondiscriminative
      skin/CAP positivity to both Vespula and Polistes. Inhibition assays were carried
      out with a CAP method, incubating the sera separately with both venoms and
      subsequently measuring the specific immunoglobulin E (IgE) to venoms themselves.
      RESULTS: Forty-five patients (33 male, mean age 40 years, age range 12-74, total
      serum IgE 242 +/- 168 kU/l) were included. Their specific IgE to Vespula and
      Polistes were 12.03 +/- 5.70 kU/l and 10.7 +/- 2.0 kU/l (P = NS), respectively.
      At the CAP-inhibition assays, in 25 patients a >75% heterologous inhibition by P.
      dominulus venom against V. vulgaris-specific IgE was found. In six subjects V.
      vulgaris venom effectively inhibited the P. dominulus-specific IgE. In the
      remaining 14 cases the CAP-inhibition test provided intermediate and not
      discriminative results. CONCLUSION: In 31/45 patients, the double sensitizations
      to venoms were probably the result of cross-reactions and the CAP-inhibition
      allowed identifying the true double sensitizations. This approach may be helpful
      for the correct prescription of immunotherapy in the case of V. vulgaris and P.
      dominulus double positivity.

PMID- 17441798
TI  - Anaphylaxis by stevioside in infants with atopic eczema.

PMID- 17441799
TI  - Allergy due to Phytolacca dioica.

PMID- 17441800
TI  - Allergic rhinitis in the Italian population evaluated through the national
      database of general practitioners.

PMID- 17441801
TI  - Niox and Niox Mino: comparison of exhaled NO in grass pollen allergic adult
      volunteers.

PMID- 17441802
TI  - Hepatitis C virus infection among HIV-1 infected individuals from northern
      Mexico.
AB  - AIMS: The prevalence of hepatitis C virus (HCV) infection, risk factors and HCV
      genotypes in 140 HIV-1 infected individuals from northern Mexico was determined.
      METHODS: Hepatitis C infection was confirmed by the detection of anti-HCV
      antibodies and HCV-RNA in sera, and genotyping was performed by the InnoLiPA-HCV
      genotype assay. RESULTS: Seventeen (12.1%) out of 140 HIV-infected individuals
      were found to be HCV-positive. Coinfected individuals were more likely to be male
      (87%). The most frequent genotype was 1a (41%), followed by 1b (29.4%), 2a/c
      (17.6%), 2b (5.9%) and 3 (5.9%). Serum transaminase concentrations (AST and ALT)
      were higher in coinfected patients. Among the risk factors for coinfection:
      sexual transmission was the most frequently observed (men who have sex with men
      (MSM); 64.7% and bisexual behavior; 64.7%) followed by intravenous drug users
      (IVDU) (53%). There was no association of the HCV genotypes with the age and risk
      factors for HIV-1 and HCV infection observed in the studied patients. CONCLUSION:
      The results suggest that the prevalence of HIV-1/HCV coinfection in Mexico is
      lower than in other American countries.

PMID- 17441803
TI  - High-dose vitamins E and C supplementation prevents ribavirin-induced hemolytic
      anemia in patients with chronic hepatitis C.
AB  - AIM: In combination therapy using interferon (IFN) and ribavirin for chronic
      hepatitis C, reduced doses should be used due to ribavirin-induced hemolytic
      anemia. The present study aimed to elucidate whether high-dose vitamins E and C
      supplementation attenuated ribavirin-induced hemolytic anemia. METHODS: Twenty
      one consecutive patients with chronic hepatitis C were enrolled in this study
      between July 2003 and December 2004, and received high-dose vitamins E (2000 mg)
      and C (2000 mg) supplementation, daily, in addition to IFN alfa-2b and ribavirin
      combination therapy (vitamins E/C group). Twenty-one sex- and age-matched
      patients who received a standard regimen of IFN alfa-2b and ribavirin for chronic
      hepatitis C between January 2001 and June 2003 were evaluated as the control
      group. RESULTS: Decrease in hemoglobin level was significantly prevented in the
      vitamins E and C group compared to that in the control group (P = 0.029). Three
      (14.3%) patients in the control group discontinued treatment because of anemia,
      while no treated patient dropped out of the study due to anemia. Sustained
      virological response was not significantly different between the two groups.
      CONCLUSION: High-dose vitamins E and C supplementation prevented ribavirin
      induced hemolytic anemia during combination therapy with ribavirin and IFN alfa
      2b in patients with chronic hepatitis C.

PMID- 17441804
TI  - Triple therapy of initial high-dose interferon with ribavirin and amantadine for
      patients with chronic hepatitis C.
AB  - AIMS: We previously reported the potential effect of combination therapy of an
      initial high-dose interferon (IFN) and amantadine on the eradication of HCV-RNA
      in patients with chronic hepatitis C. The additive effects of amantadine on
      interferon and ribavirin combination therapy remain controversial. In this study
      we investigated the efficacy of initial high-dose IFN with ribavirin and
      amantadine on the virological response in patients with chronic hepatitis C with
      a high viral load of genotype 1b. METHODS: Twenty-two patients with high viral
      loads of genotype 1b hepatitis C virus were enrolled in this pilot study.
      Patients were administered IFN-beta for four weeks and then IFN-alpha2b for 22
      weeks with daily oral administration of ribavirin and amantadine. RESULTS: A
      sustained virological response (SVR) was shown in 31.8% (seven of 22 patients).
      With the naive patients, the SVR rate was 21.4% (three of 14 patients). In
      patients who could not eradicate HCV-RNA by previous IFN monotherapy, the SVR
      rate was 50% (four of eight patients). CONCLUSION: Triple therapy with an initial
      high dose of IFN with ribavirin and amantadine may be effective, especially for
      chronic hepatitis C IFN-retreatment patients with a high viral load of genotype
      1b.

PMID- 17441805
TI  - Diabetes mellitus reduces the therapeutic effectiveness of interferon-alpha2b
      plus ribavirin therapy in patients with chronic hepatitis C.
AB  - AIM: Patients with chronic hepatitis C (CHC) often have diabetes mellitus (DM).
      However, it is unknown whether DM affects patient response to interferon (IFN)
      plus ribavirin therapy. Therefore, the aim of this study was to examine the
      influence of DM on the outcome of IFN-alpha2b plus ribavirin therapy. METHODS: In
      a cohort of 110 patients with CHC, the outcome of 6 months of IFN-alpha2b plus
      ribavirin therapy was evaluated by comparing the patients with and without DM.
      RESULTS: There were 46 sustained-responders; 64 patients did not become sustained
      responders. Higher age (P = 0.015), lower platelet counts (P = 0.036), hepatitis
      C virus (HCV) serotype 1 (P = 0.001), advanced liver fibrosis (P = 0.004), and
      the presence of DM (P = 0.007) were significantly associated with not becoming a
      sustained-responder. Seventeen CHC (15%) patients had DM. Sex ratio, age, body
      mass index, alanine aminotransferase levels, HCV-RNA titer, and HCV serotypes did
      not significantly differ between the patients with and without DM, while fasting
      plasma glucose, hemoglobin A1c and liver histological staging were significantly
      different. On multiple logistic regression analysis, HCV serotype 1 (odds ratio
      8.743, 95% confidence interval 2.215-34.517; P = 0.002) and the presence of DM
      (odds ratio 8.657, 95% confidence interval 1.462-51.276; P = 0.014) were
      independently associated with not becoming a sustained-responder. CONCLUSIONS:
      The findings indicate that DM reduces the response to IFN-alpha2b plus ribavirin
      therapy in CHC patients.

PMID- 17441806
TI  - Hepatitis C virus genotype distribution in Myanmar: Predominance of genotype 6
      and existence of new genotype 6 subtype.
AB  - AIM: This study was performed to determine the prevalence and distribution of
      hepatitis C virus (HCV) genotypes in Myanmar. METHODS: A total of 1333 peripheral
      blood samples were collected from four different border cities of Myanmar. The
      anti-HCV antibody-positive serum samples were identified. HCV was genotyped by
      reverse transcriptase polymerase chain reaction, direct DNA sequencing and
      phylogenetic analysis on the partial core genome. RESULTS: The overall prevalence
      of HCV infection was 11.6% (154/1333). Regionally, it was 13.5% (47/349) in the
      north-eastern city, 12.8% (64/501) in the north-western city, 4.2% (16/380) in
      the southern city and 26.2% (27/103) in the western city. HCV was genotyped in
      145/154 (94.2%) samples. Genotype 6 was the most prevalent genotype in this study
      (71/145, 49%), followed by genotype 3 (57/145, 39.3%), genotype 1 (16/145, 11%),
      and genotype 2 (1/145, 0.7%). Genotype 6 was mostly found in the northern cities
      and genotype 3 in the southern and western cities of Myanmar. Multiple HCV
      genotypes/subtypes were successfully characterized as 1a, 1b, 2a, 3a, 3b, 6m, 6n,
      and a new 6 subtype. Among them, subtype 6n was the most predominant subtype
      (38.6%), followed by subtype 3b (29.7%), 3a (9.6%), 6m (9%), 1b (6.9%), 1a
      (4.1%), new 6 subtype (1.4%) and 2a (0.7%). Subtype 6n was more widely
      distributed in the northern cities whereas subtype 3b was more common in the
      western city. The newly discovered genotype 6 subtype was from the northern
      cities. CONCLUSIONS: The results indicate there are regional differences of HCV
      genotype distribution in Myanmar. There is a distinct geographic variation from
      other South-East Asian countries in terms of the existence of the new genotype 6
      subtype.

PMID- 17441807
TI  - Continuous normothermic hemihepatic vascular inflow occlusion over 60 min for
      hepatectomy in patients with cirrhosis caused by hepatitis B virus.
AB  - AIM: To evaluate the safety of remnant liver in cirrhotic patients who had
      undergone irregular hepatectomy with continuous normothermic hemihepatic vascular
      inflow occlusion for over 60 min. METHODS: A group of 133 cirrhotic patients who
      had hepatitis B virus accompanied by hepatocellular carcinoma and had undergone
      irregular hepatectomy by hemihepatic vascular inflow occlusion was studied.
      According to the time of hemihepatic vascular inflow occlusion, patients were
      assigned either to the control group, treatment(60) group, or treatment(90)
      group. The quantity of blood loss and blood transfusion, routine liver
      biochemistry and postoperative complications were retrospectively analyzed.
      RESULTS: The data showed that there were no significant differences in
      postoperative complications between the three groups. Compared to the
      preoperative day, the levels of aspartate transaminase (AST), alanine
      transaminase (ALT), prothrombin time (PT) and serum bilirubin on postoperative
      days 1 and 3 were significantly increased in all three groups and the levels of
      albumin and platelet were significantly decreased on postoperative day 1.
      Duration of hospital stay and the levels of ALT and AST on postoperative days 1,
      3 and 7 were higher in the treatment(90) group than in the control group and
      treatment(60) group (P < 0.05). However, no significant differences were
      displayed in the length of hospital stay and the levels of AST, ALT, PT, albumin,
      platelet count and serum bilirubin on postoperative days 1, 3 and 7 between the
      control group and the treatment(60) group (P > 0.05). CONCLUSION: Hemihepatic
      vascular inflow occlusion over 60 min is a possible method for irregular
      hepatectomy in patients with cirrhosis caused by the hepatitis B virus. However,
      caution must be exercised in utilizing this method where the time of vascular
      occlusion is over 90 min.

PMID- 17441808
TI  - Vascular endothelial growth factor does not improve liver regeneration and
      survival after 90% subtotal liver resection.
AB  - AIM: Vascular endothelial growth factor (VEGF) has been shown to stimulate liver
      regeneration after 70% partial hepatectomy (PH). It is unclear, however, whether
      exogenous administration of VEGF can also be used to improve liver regeneration
      and survival after 90% subtotal liver resection. The aim of this study was to
      determine the effect of exogenous and endogenous VEGF after 90% subtotal
      hepatectomy (SH). METHODS: Rats were subjected to 90% SH and treated with VEGF,
      anti-VEGF or NaCl. Postoperatively (3 h - 5 days) liver body weight ratio (LBR),
      hepatocyte proliferation and biochemical markers were assessed. ELISA was
      performed to measure protein levels for VEGF. Gene expression was determined by
      customized cDNA arrays and quantitative RT-PCR. RESULTS: Administration of VEGF
      did not enhance LBR or hepatic proliferation, or reduce the serum parameters.
      VEGF levels were the highest in VEGF-treated animals. The overall survival after
      90% SH reached 78% in VEGF-treated animals, but did not differ significantly from
      that of anti-VEGF or NaCl-treated animals (74% and 75%, respectively). Gene
      expression analysis showed a modulation of anti-apoptotic and cell cycle control
      genes that was independent of VEGF. CONCLUSIONS: In contrast to PH, liver
      regeneration and survival after SH cannot be modulated by VEGF. This indicates
      that the relevant mechanisms that stimulate liver regeneration after hepatectomy
      at least partially depend upon the extent of liver resection.

PMID- 17441809
TI  - Vitamin K2 inhibits the proliferation of HepG2 cells by up-regulating the
      transcription of p21 gene.
AB  - AIM: Vitamin K2 has been reported to inhibit the growth of human hepatocellular
      carcinoma (HCC) in vitro and suppress hepatocarcinogenesis in vivo. However, its
      inhibitory mechanism has not yet been clarified. METHODS: Different
      concentrations of vitamin K2 (30, 10, 1, 0.1 and 0.01 muM) were added to the HCC
      cell line HepG2 to assess effects on cell growth. The effect of vitamin K2 on
      cell cycle progression was determined by flow-cytometric analysis. The expression
      of cell cycle regulatory proteins p21 and p27 was then examined by Western blot.
      Whether vitamin K2 regulates the gene expression through action on the p21
      promoter region was investigated by luciferase assay. RESULTS: Vitamin K2
      inhibited the growth of HepG2 cells dose-dependently, and its inhibitory rate
      reached approximately 50% at the dose of 30 muM after 96 h treatment. After
      treatment with vitamin K2, the proportion of cells in G0-G1 phase increased, and
      in S phase decreased. Apoptotic cells were not detected. The expression of cell
      cycle regulatory protein p21 was induced by vitamin K2 treatment, but p27 was
      not. By the luciferase assay, vitamin K2 significantly activated the promoter of
      p21. Knock-down of p21 by siRNA reversed the growth inhibition of HepG2 cells by
      vitamin K2. CONCLUSIONS: The findings suggest that vitamin K2 suppresses the
      proliferation of HCC cells by blocking the cell cycle G1/S progression through
      the transcriptional induction of p21.

PMID- 17441810
TI  - Inhibition of hepatocellular carcinoma growth by antisense oligonucleotides to
      type I insulin-like growth factor receptor in vitro and in an orthotopic model.
AB  - AIM: The type I insulin-like growth factor receptor (IGF-IR) is overexpressed in
      many tumors including human hepatocellular carcinoma (HCC). It is a critical
      signaling molecule for tumor cell proliferation and survival. In the present
      study, IGF-IR expression was down-regulated by phosphorothioate antisense
      oligonucleotides (AS[S]ODN) to evaluate their specific effects on growth of
      hepatoma cells in vitro and in vivo. METHODS: HepG2 cells were transfected with
      different doses of AS[S]ODN, sense [S]ODN, mismatch [S]ODN, or Lipofectin for 72
      h, and cell proliferation was analyzed by MTS assay. In vivo, an orthotopic
      transplant model of HCC was established in nude mice, which were then injected
      with AS[S]ODN, sense [S]ODN, 5-fluorouracil or saline. At the endpoint of
      treatment, the tumors were excised and evaluated. RESULTS: Compared to sense and
      mismatched oligonucleotides, AS[S]ODN targeting to IGF-IR mRNA significantly
      inhibited hepatoma cell lines HepG2 proliferation and IGF-IR expression at both
      mRNA and protein levels. The in vivo results showed that systemic treatment also
      resulted in significant inhibition in tumor growth. Tumor growth in mice treated
      with AS[S]ODN (50 and 75 mg/kg per day) was significantly inhibited (71.81% and
      61.74%, respectively) compared to the saline-treated group (P < 0.01) in a dose
      dependent manner. The antitumor effect of IGF-IR AS[S]ODN was associated with
      down-regulation of IGF-IR in tumor xenografts. Furthermore, IGF-IR AS[S]ODN
      prevented liver recurrence tumor growth and metastasis in the lung, showing a
      dose-dependent response. The level of serum alpha-fetoprotein in AS[S]ODN-treated
      groups was also decreased in a dose-dependent manner, and a good correlation was
      observed between tumor volume and serum alpha-fetoprotein concentration.
      CONCLUSIONS: These data suggest that IGF-IR AS[S]ODN can effectively and
      specifically inhibit HCC growth in vitro and in vivo. Blockage of IGF-IR
      expression could be a promising therapeutic approach for the management of
      patients with HCC.

PMID- 17441811
TI  - Silencing MAT2A gene by RNA interference inhibited cell growth and induced
      apoptosis in human hepatoma cells.
AB  - AIMS: A switch in gene expression from MAT1A to MAT2A was found in liver cancer,
      suggesting that MAT2A plays an important role in facilitating cancer growth.
      MAT2A is an interesting target for antineoplastic therapy. The molecular
      mechanisms of silencing MAT2A by RNA interference inhibited cell growth and
      induced apoptosis in hepatoma cells was studied. METHODS: We investigated the
      effects of MAT2A on S-adenosyl-methionine (SAM) production, cell growth and
      apoptotic cell death in hepatoma cell lines (Bel-7402, HepG2, and Hep3B) using an
      RNA interference approach. RESULTS: The treatment of three hepatoma cell lines
      with small interfering RNA (siRNA) targeting to the MAT2A gene resulted in
      reducing the MAT II activity, facilitating SAM production, increasing SAM : SAH
      ratio, inhibiting cell growth and inducing cell apoptosis in hepatoma cells. In
      addition, silencing MAT2A gene resulted in the stimulation of MAT1A mRNA
      production, which was blocked by 3-deazaadenosine and l-ethionine, but not d
      ethionine, suggesting that such effect was specific and mediated by upregulation
      of SAM level and SAM : S-adenosylethionine (SAH) ratio. CONCLUSION: Silencing
      MAT2A by sequence-specific small interfering RNA caused a switch of MAT gene
      expression from MAT2A to MAT1A, which led the content of SAM to change to a
      higher steady-state level that resulted in the inhibition of cell growth and the
      induction of apoptotic cell death in human hepatoma cells. These results also
      suggested that MAT2A may hold potential as a new target for liver cancer gene
      therapy.

PMID- 17441812
TI  - Epigenetic and genetic alterations of PTEN in hepatocellular carcinoma.
AB  - AIM: To investigate the roles of epigenetic and genetic alterations of the
      phosphatase and tensin homologue on chromosome 10 gene (PTEN) in carcinogenesis
      and the development of hepatocellular carcinomas (HCC). METHODS: A total of 56
      cases of HCC tissues and six liver cell lines were studied for the expression of
      PTEN by immunohistochemistry and Western blot analysis. The PTEN gene mutations
      in exon5 and exon8 were detected by a combination of single-strand conformation
      polymorphism (SSCP) analysis and DNA sequencing. Methylation-specific PCR (MSP)
      was used to identify PTEN promoter methylation. RESULTS: Of the 56 cases of HCC,
      24 (42.9%) expressed the PTEN protein. All surrounding liver tissues of the
      hepatoma (32 cases) were positive for PTEN. Of the six cell lines, three liver
      cancer cell lines showed a low expression of PTEN. Five mutations of 56 HCC
      samples were detected. All of them were located at intron4. No mutation was found
      in exon5 and exon8. After MSP analysis, we found nine cases of PTEN promoter
      methylation in 56 specimens (16.1%). However, no CpG island of PTEN was found to
      be methylated in all six liver cell lines. CONCLUSION: The level of PTEN protein
      was altered in part of the HCC. The downregulation of PTEN expression may not be
      mainly associated with the PTEN mutations, but partly due to PTEN promoter
      methylation and other epigenetic regulation.

PMID- 17441813
TI  - The cost of change on the land.

PMID- 17441814
TI  - headspace: National Youth Mental Health Foundation: making headway with rural
      young people and their mental health.
AB  - Mental health is the number one health issue affecting young people in Australia
      today, yet only one in four of these young people receive professional help.
      Approximately 14% of 12- to 17-year-olds and 27% of 18- to 25-year-olds
      experience mental health problems each year. However, many do not have ready
      access to treatment or are reluctant to seek that help. These issues might be
      exacerbated in the rural and remote regions of Australia where sociocultural
      barriers such as stigma, lack of anonymity and logistic difficulties including
      cost and availability of transport can hinder young people accessing mental
      health services. headspace: the National Youth Mental Health Foundation has been
      funded to address these issues. headspace will provide funding for the
      establishment of communities of youth services across Australia, provide national
      and local community awareness campaigns and plans, establish a centre of
      excellence that will identify and disseminate evidence-based practice in
      addressing youth mental health issues, and translate findings into education and
      training programs that are targeted at service providers to work with youth
      mental health. The communities of youth services will build the capacity of local
      communities to identify early, and provide effective responses to, young people
      aged 12-25 years with mental health and related substance use disorders. Specific
      approaches in rural, regional and remote areas will be developed as well as
      specific programs to involve young Indigenous people.

PMID- 17441815
TI  - Internet-based mental health programs: a powerful tool in the rural medical kit.
AB  - OBJECTIVE: To discuss, using two case examples, the potential utility of Internet
      based depression information and automated therapy programs in rural regions.
      DESIGN: Systematic review of evaluations of two Australian web-based mental
      health programs: MoodGYM and BluePages Depression Information. SETTING:
      Community, school, university. PARTICIPANTS: A total of 12 papers and reports
      derived from nine separate studies of MoodGYM and BluePages involving sample
      sizes ranging from 78 to 19 607 people. OUTCOME MEASURES: Depressive symptoms,
      anxiety symptoms, dysfunctional thoughts, depression literacy, stigma, help
      seeking and cost-effectiveness. RESULTS: Internet-based applications were
      effective in reducing depressive symptoms and stigmatising attitudes to
      depression and in improving depression literacy. School-based programs also
      showed promise in decreasing depressive symptoms. CONCLUSIONS: Depression self
      help and information programs can be delivered effectively by means of the
      Internet. As accessibility of face-to-face mental health services in rural areas
      is poor and as there is a strong culture of self-reliance and preference for self
      managing health problems among rural residents, the Internet might offer an
      important platform for the delivery of help for depression in rural regions.
      Consideration should be given to developing programs tailored to rural settings
      and future research should evaluate the efficacy and effectiveness of such
      programs in rural settings.

PMID- 17441816
TI  - Disadvantage and discontent: a review of issues relevant to the mental health of
      rural and remote Indigenous Australians.
AB  - OBJECTIVE: To provide an overview of the mental health of Aboriginal and Torres
      Strait Islander residents of rural and remote Australia and to identify
      associated factors. FINDINGS: Indigenous Australians have higher rates of serious
      mental disorders and of mental health problems associated with social
      disadvantage. This disadvantage is greater for Indigenous Australians living
      outside metropolitan centres. Contrary to romanticised constructions of remote
      Aboriginal Australia, those living in such settings are not immune to such
      hardship - which is often unrelenting. The psychological and behavioural problems
      that emerge as a result are compounded by narrowly focused and inadequate mental
      health services, with children being particularly vulnerable. CONCLUSION:
      Indigenous residents of rural and remote Australia experience high levels of
      mental disorder. Although addressing the predisposing social disadvantage will
      demand significant whole-of-government investment, ensuring equitable access to
      effective mental health services is an immediate priority.

PMID- 17441817
TI  - Securing and retaining a mental health workforce in Far Western New South Wales.
AB  - OBJECTIVE: To identify strategies local managers can use to optimise recruitment
      and retention of mental health staff in rural locations. DESIGN: Forty-one staff
      were interviewed about factors that attracted them to work in remote locations,
      their initial intentions and factors that encourage them to stay. SETTING: The
      former Far West Health Area of New South Wales. RESULTS: Overall job satisfaction
      was high (68%). Key attractors were rural lifestyle and environment. Family
      reasons, the field of work and the rural lifestyle were factors that keep staff
      in their positions. Some mentioned the desire to achieve professional goals and
      see projects completed. Many staff reported that their initial intentions to stay
      had remained the same (43.9%). Reasons for extended intention to stay were:
      greater career opportunities; a desire to complete professional goals; extension
      of positions; and personal factors. The most common reason for leaving was better
      career opportunities. Other reasons included: changes to personal commitments;
      heavy workloads or burnout; service management; and workplace politics. A large
      number of respondents mentioned key differences when comparing rural and
      metropolitan areas: more travel (greater distances); less service options for
      referral; greater spectrum of illnesses and conditions; more autonomy and
      responsibility. CONCLUSIONS: Strategies to recruit and retain staff must take
      account of personal needs and aspirations. While there is room for state
      strategies to improve employment incentives, there is also considerable scope for
      local managers to improve the design and attractiveness of jobs.

PMID- 17441818
TI  - Use of social network analysis to describe service links for farmers' mental
      health.
AB  - OBJECTIVE: The primary mental health care needs of farmers require that service
      innovations incorporate rural support workers into a local service network. This
      component of the FarmLink pilot sought to develop a social network analysis
      method that would describe local mental health-related human service networks.
      The purpose is to inform improvements in this network and to serve as a baseline
      against which such improvements can be evaluated. DESIGN: A pilot survey of rural
      human service providers who deal with mental health-related issues among farmers
      about their self-reported links between each other. SETTING: Service delivery
      agencies associated with a small rural town in New South Wales. PARTICIPANTS:
      Twenty-five agents from a range of human services involved in rural human support
      services to farmers, such as from agricultural and drought support, welfare,
      primary health care and education. INTERVENTION: Telephone interview prior to the
      conduct of a Mental Health First Aid seminar and a Farmers Mental Health and
      Wellbeing workshop. MAIN OUTCOME MEASURES: Agent self-reported service links over
      the past three months for information exchange, client referrals and working
      together in relation to helping farmers for mental health, emotional health or
      stress-related problems. Analysis trialled on the 'made referrals' link shows the
      network influence, prominence and intermediary status of the rural financial
      counsellor. CONCLUSIONS: Within the limitations of recalled self-report data,
      social network analysis provides a useful network description for informing and
      evaluating service network improvements.

PMID- 17441819
TI  - Evaluation of a stress management course in adult education centres in rural
      Australia.
AB  - OBJECTIVE: To investigate whether attending a six-week stress management course
      in a rural adult education centre is effective in reducing participants' levels
      of stress, anxiety and depression. DESIGN: Repeated measures design using self
      report measures of stress, anxiety and depression at commencement and completion
      of a six-week stress management course, and six months post-completion follow up.
      SETTING AND PARTICIPANTS: One hundred and thirty-two adults (age range 18-73
      years) living in a rural community who self-enrolled in the stress management
      course at adult education centres. INTERVENTION: The course consisted of six
      weekly group sessions. Each two-hour session conducted by mental health
      professionals, included teaching cognitive behavioural strategies targeted at
      reducing individual symptoms of stress. MAIN OUTCOME MEASURES: Comparative
      analysis of pre- and post-test and six-month follow up on measures of stress
      (Stress Symptom Checklist), anxiety and depression (Hospital Anxiety and
      Depression Scale). RESULTS: RESULTS indicated a significant reduction in stress
      symptoms (F(7,90) = 34.92, P < 0.001), anxiety and depression (F(3,95) = 87.92, P
      < 0.001) from course commencement to course completion. These improvements were
      sustained six months after course completion for stress symptoms (F(11,65) =
      22.40, P < 0.001), anxiety and depression (F(5,73) = 41.78, P < 0.001).
      CONCLUSION: Findings demonstrate the stress management course is an effective
      community intervention in a rural community. Challenges for future implementation
      of the program are discussed.

PMID- 17441820
TI  - Prevalence of psychological distress, anxiety and depression in rural communities
      in Australia.
AB  - OBJECTIVE: To describe the prevalence of psychological distress, depression and
      anxiety in three Australian rural settings and to identify the levels of risk by
      gender and age. DESIGN AND SETTING: Three cross-sectional surveys in the Greater
      Green Triangle area covering the south-east of South Australia (Limestone Coast),
      and south-west (Corangamite Shire) and north-west (Wimmera) of Victoria.
      PARTICIPANTS: A total of 1563 people, aged 25-74 years, randomly selected from
      the electoral roll. MAIN OUTCOME MEASURES: Psychological distress assessed by the
      Kessler 10, and anxiety and depression assessed by the Hospital Anxiety and
      Depression Scale. RESULTS: The prevalence of psychological distress was 31% for
      both men and women with two-thirds reporting moderate and one-third high levels
      of psychological distress. The prevalence of depression and anxiety was
      approximately 10%. The highest rate of psychological distress, anxiety and
      depression occurred in the 45-54 years age group. There were no consistent gender
      or area differences in the prevalence of psychological distress, depression or
      anxiety. CONCLUSIONS: A third of the rural population reported psychological
      distress, with the highest prevalence observed in middle-aged men and women.
      Thus, health professionals should attend not only to physical health, but also to
      mental health status in this age group. It is also important to target prevention
      strategies at the 20% who reported moderate levels of psychological distress in
      order to prevent the development of more serious conditions.

PMID- 17441821
TI  - Natural disasters, climate change and mental health considerations for rural
      Australia.
AB  - This paper addresses a very salient feature of rural life and landscapes in
      Australia, natural disasters, and offers a psychological perspective on
      individual and community perceptions, responses, preparedness and planning. The
      convergent perspective offered reflects research and practice findings and
      insights from social and environmental psychology, as well as clinical, health
      and community psychology. The objective is to briefly characterise how these
      psychological approaches frame the psychological and social reality of these
      threats and events, and to canvas what insights and evidence-based best practice
      psychology have to offer allied professionals and paraprofessionals, and rural
      communities, as they experience and come to terms with the vagaries and extremes
      of the Australian environment.

PMID- 17441822
TI  - Challenges faced by general practitioners and allied mental health services in
      providing mental health services in rural Queensland.
AB  - OBJECTIVE: To examine the views of rural practitioners concerning issues and
      challenges in mental health service delivery and possible solutions. DESIGN: A
      qualitative study using individual semi-structured interviews. SETTING: Eight
      general practices from eight rural Queensland towns, three rural mental health
      services and two non-government organisations, with interviews being conducted
      before recent changes in government-subsidised access to allied health
      practitioners. PARTICIPANTS: A sample of 37 GPs, 19 Queensland Health mental
      health staff and 18 participants from community organisations. MAIN OUTCOME
      MEASURES: Analysis of qualitative themes from questions about the key mental
      health issues facing the town, how they might be addressed and what challenges
      would be faced in addressing them. RESULTS: There was substantial consensus that
      there are significant problems with inter-service communication and liaison, and
      that improved collaboration and shared care will form a critical part of any
      effective solution. Differences between groups reflected differing organisational
      contexts and priorities, and limitations to the understanding each had of the
      challenges that other groups were facing. CONCLUSIONS: Improvements to mental
      health staffing and to access to allied health might increase the ability of GPs
      to meet the needs of less complex patients, but specific strategies to promote
      better integrated services are required to address the needs of rural and
      regional patients with complex mental health problems. The current study provides
      a baseline against which effects of recent initiatives to improve mental health
      care can be assessed.

PMID- 17441823
TI  - Mental health issues and resources in rural and regional communities: an
      exploration of perceptions of service providers.
AB  - OBJECTIVE: To identify service providers' and community organisations'
      perceptions of the resources available to support people with mental illness and
      the unmet needs of this client group in rural Queensland. DESIGN: An exploratory
      study was undertaken involving focus group interviews across the study sites.
      SETTING: Five regional towns in rural Queensland. PARTICIPANTS: Ten to 14 members
      were recruited for each of the five focus groups. The groups represented a
      diverse mix of participants including health and community service providers and
      representatives from community organisations. RESULTS: Participants identified
      gaps in services in relation to health, employment and education, housing and
      accommodation, transport and social inclusion and health promotion. Inter-service
      communication and inappropriate funding models were themes affecting service
      delivery. CONCLUSIONS: Specific service issues of housing and transport were
      identified to be particularly problematic for people with mental illness across
      all towns. Intersectoral communication and funding models require further
      research.

PMID- 17441824
TI  - Identifying depression in patients following admission for acute coronary
      syndrome.

PMID- 17441832
TI  - Neuroimaging and neurologic complications after organ transplantation.
AB  - Neurologic complications are common after transplantation and affect 30-60% of
      transplant recipients. The etiology of most of the posttransplant neurologic
      disorders is related to the opportunistic infections, both systemic and involving
      central nervous system (CNS), toxicity of immunosuppressive medications, and the
      metabolic insult created by the underlying primary disease and the transplant
      procedure. Neuroimaging studies are one of the key tools in the evaluation and
      enable early diagnosis of neurologic complications in transplant patients,
      especially posterior reversible leukoencephalopathy syndrome, central pontine
      myelinolysis, intracerebral hemorrhage, and fungal and bacterial abscesses.
      Magnetic resonance imaging (MRI) is the preferred technique, but each of the
      available neuroimaging techniques offers a unique insight into the
      pathophysiologic mechanisms underlying neurologic complications of
      transplantation. The role of neuroimaging in this population includes early
      detection of calcineurin inhibitor neurotoxicity, opportunistic infections,
      neoplasia, metabolic disorders, or cerebrovascular diseases. In addition, we can
      monitor longitudinal progression of disease and treatment response.

PMID- 17441833
TI  - Mechanical disruption of thrombus following intravenous tissue plasminogen
      activator for ischemic stroke.
AB  - BACKGROUND AND PURPOSE: We prospectively evaluated the safety of aggressive
      mechanical disruption of thrombus following full-dose intravenous (IV)
      recombinant tissue plasminogen activator (rt-PA) to treat ischemic stroke in 24
      patients with an initial National Institutes of Health stroke scale (NIHSS) score
      of >or=10. METHODS: Clinical evaluations were performed at presentation and 24
      hours, 7 to 10 days, and 1 to 3 months (using modified Rankin scale) after
      treatment. These end points were compared to matched historical controls treated
      with IV rt-PA alone. RESULTS: Of the 24 patients, mechanical disruption was
      undertaken in 17 patients with persistent angiographic occlusion using
      microcatheter exploration (n= 3), angioplasty (n= 5), snare maneuvers (n= 7), and
      combination of both (n= 2). Partial or complete recanalization was observed in 10
      of the 17 patients. Neurological improvement at 24 hours (>or=4 point reduction
      in NIHSS score) was observed in 11 of 17 patients. Comparisons with matched
      controls suggest potential equivalence for symptomatic ICH (0% vs 12%),
      asymptomatic ICH (18% vs 15%), and early neurological improvement (65% vs 53%).
      CONCLUSION: The study shows that aggressive mechanical thrombus disruption in
      large artery occlusion in the setting of acute ischemic stroke is safe with
      acceptable rates of ICH and promotes angiographic recanalization.

PMID- 17441834
TI  - Pattern of cortex and white matter involvement in severe middle cerebral artery
      ischemia.
AB  - BACKGROUND AND PURPOSE: In middle cerebral artery (MCA) stroke, ischemia usually
      is unevenly distributed within the MCA territory. We sought to investigate which
      brain structures are critical for the acute neurological deficit in severe MCA
      stroke. METHODS: We used magnetic resonance (MR) imaging and statistical
      parametric mapping in 64 consecutive stroke patients (64 +/-13 years) to study
      the pattern of the initial perfusion abnormality. RESULTS: Patients with lesion
      progression had more severe time-to-peak (TTP) abnormalities (P < .0001) in the
      inferior frontal gyrus, superior temporal gyrus, insula, and underlying
      hemispheric white matter than those with lesion regression. Also, patients with
      lesion progression had more severe T2 abnormalities on day 8 than those with
      lesion regression. In contrast, the changes of water diffusion were similar among
      the two groups resulting in a perfusion-diffusion mismatch in lesion progression.
      TTP-lesions were related to the neurological deficit score (r(s)=-0.563, P <
      .0001), T2-lesions (r= 0.686, P < .0001), and cerebral artery abnormalities
      assessed on MR-angiography (r(s)= 0.399, P < .01). CONCLUSIONS: In major MCA,
      stroke ischemia was most severe in the central portion of the MCA territory. It
      is suggested that involvement of hemispheric white matter accentuated the
      neurological deficit probably by affecting cortico-cortical and cortico
      subcortical fibers.

PMID- 17441835
TI  - Internal carotid aplasia/hypoplasia and intracranial saccular aneurysms: series
      of three new cases and systematic review of the literature.
AB  - BACKGROUND AND PURPOSE: Abnormal arterial flow dynamics and intracranial
      collateral pathways can be seen in patients with congenital internal carotid
      artery (ICA) aplasia or hypoplasia. Here we seek to evaluate whether ICA
      aplasia/hypoplasia is associated with an increased prevalence of intracranial
      saccular aneurysm relative to carotid rete mirabile. METHODS: We combined our
      experience of three cases with 148 previous publications to form a retrospective
      series including 132 cases of ICA aplasia, 33 cases of ICA hypoplasia, and 34
      cases of carotid rete mirabile. RESULTS: After excluding cases lacking
      angiograms, ICA aplasia/hypoplasia was more commonly associated with aneurysm
      (45/158, 27.8%) compared with rete mirabile (2/34, 5.9%). A significantly greater
      overall aneurysm prevalence was seen among ICA aplasia/hypoplasia patients age 30
      years or older (38/101, 36.6%) than in younger individuals (7/48, 14.6%).
      CONCLUSIONS: Intracranial saccular aneurysm is more strongly associated with ICA
      aplasia/hypoplasia than rete mirabile. An increased aneurysm prevalence among
      older individuals with ICA aplasia/hypoplasia suggests an acquired etiology.
      Magnetic resonance angiography (MRA) is recommended in the initial evaluation of
      ICA aplasia/hypoplasia to evaluate for intracranial saccular aneurysm,
      particularly after the third decade of life.

PMID- 17441836
TI  - Focal atrophy and cerebrovascular disease increase dementia risk among
      cognitively normal older adults.
AB  - BACKGROUND AND PURPOSE: This study investigated the association of medial
      temporal lobe (MTL) atrophy and cerebrovascular disease (white matter
      hyperintensities [WMH], subclinical infarcts) with the risk of developing
      Alzheimer's disease (AD) among cognitively normal older adults. METHODS: Risk of
      developing AD was examined for 155 cognitively normal older adults (77.4 years,
      60% women, 81% white). The MTL volumes and the presence of WMH and of subclinical
      infarcts were determined from brain magnetic resonance imaging (MRI) at the
      beginning of the study. Follow-up cognitive evaluations (average 4.3 years)
      identified those who developed AD. RESULTS: The presence of either MTL atrophy or
      subclinical infarcts was independently and significantly associated with a
      greater risk to develop AD (OR [95% CI]: 4.4 [1.5, 12.3] and 2.7 [1.0, 7.1],
      respectively). In addition, those participants with both MTL atrophy and at least
      one brain infarct had a 7-fold increase in the risk of developing AD (OR [95%
      CI]: 7.0 [1.5, 33.1]), compared to those who had neither of these conditions.
      CONCLUSIONS: In cognitively normal older adults, markers of neurodegeneration (as
      reflected by MTL atrophy) and of cerebrovascular disease (as reflected by
      infarcts on MRI) independently contribute to the risk to develop AD.

PMID- 17441837
TI  - Multislice brain myelin water fractions at 3T in multiple sclerosis.
AB  - PURPOSE: To evaluate a multislice nonlinearly-spaced 12-echo imaging sequence at
      3T covering the supratentorial brain for the quantification of myelin water
      fraction (MWF) in multiple sclerosis (MS) patients. METHODS: Eighty-nine patients
      with, or at risk of, MS (69 relapsing remitting MS [RRMS], 7 secondary
      progressive MS [SPMS], 13 clinically isolated syndrome [CIS]) and 28 controls
      were studied. Twelve-echo datasets were acquired using a multislice T2 prep
      spiral imaging sequence and were fitted using a nonnegative least squares
      algorithm. The mean MWF within normal appearing white matter (NAWM), contrast
      enhancing (CE), and nonenhancing T2 lesions were calculated. RESULTS: Mean MWF in
      white matter for controls was 11.3%. Mean MWF was significantly reduced in NAWM
      of MS patients (10.6%, P= .004) relative to controls. SPMS/RRMS patients with
      disease duration >5 years (10.3%) had lower MWF compared to CIS/RRMS with disease
      duration <or=5 years (10.8%, P= .03). Mean MWF was reduced by 26% and 29% within
      both CE (P < .0001) and nonenhancing T2 lesions (P < .0001) relative to controls.
      CONCLUSIONS: Using a multicomponent T2 sequence at 3T, a significant decrease in
      the supratentorial MWF was observed in MS NAWM and lesions relative to controls.
      The method was sensitive to detect white matter changes early in the disease
      process.

PMID- 17441838
TI  - Hyperechogenicity of the substantia nigra in Parkinson's disease.
AB  - Substantia nigra (SN) was assessed by transcranial sonography (TCS) in 47
      Parkinson's disease (PD) patients and in 39 healthy volunteers. A
      semiquantitative echogenicity scale was created with arbitrary values ranging
      from 1 to 5, zones with grade >or=3 and larger than 0.19 cm(2) were recorded as
      hyperechogenic SN. TCS examination of SN as a diagnostic test for PD in our study
      showed 87.2% sensitivity and 94.9% specificity.

PMID- 17441839
TI  - Neuroimaging characteristics in subgroup of GBMs with p53 overexpression.
AB  - Glioblastoma multiforme (GBM) is a heterogeneous group of tumors, and
      neuroimaging characteristics have not been well-defined in molecular subgroups.
      Eighty-five patients with GBM were analyzed regarding imaging characteristics and
      correlation to p53 expression. The p53 positivity was graded according to
      percentage of positive cells (Grade 0, for < 10%; Grade 1, for <25%; Grade 2, for
      26-50%; Grade 3, for >50% labeled cells). Imaging characteristics evaluated in
      the preoperative MRI were location and number of lesions, dimensions of enhancing
      lesion and of surrounding edema, mass effect, tumor borders, enhancement pattern
      after intravenous contrast administration, and tumor necrosis. Eighteen tumors
      had p53 expression >50% in immunohistochemical staining. Preoperative MRI of
      patients harboring those tumors with high p53 positivity revealed typical lesions
      with ring enhancement pattern and well-defined borders in T1-weighted images with
      contrast, and they were significantly different from other groups of p53
      expression. There was no difference in terms of location and number of the
      lesions, dimensions of enhancing lesion and surrounding edema, mass effect, and
      the tumor necrosis between four different groups of p53 expression. A special
      subgroup of GBMs with p53 overexpression has ring enhancement pattern and well
      defined border on MRI that may be influential in preoperative planning and
      postoperative management of adjunct therapy.

PMID- 17441840
TI  - Delirium due to brain microembolism: diagnostic value of diffusion-weighted MRI.
AB  - Delirum is a common complication in hospitalized patients and it is characterized
      by acute disturbances of consciousness, attention, cognition, and perception.
      Despite the frequency with which it is observed, ischemic stroke is generally
      considered as an unusual cause of delirium. A subtype of brain embolism is
      characterized by multiple small emboli in different vascular territories, a
      condition known as "brain microembolism." Given the high contrast of acute
      ischemic lesions in diffusion weighted imaging (DWI) this technique is
      particularly helpful to detect these small infarctions. We present here a patient
      with pulmonary metastases who was treated with bronchial artery embolization and
      who subsequently developed delirium due to brain microembolism. The embolic
      material crossed through pulmonary arteriovenous fistulas, producing multiple
      areas of cerebral ischemia. The ischemic lesions could be visualized only on DWI,
      and they affected the periventricular region, caudate nucleus, thalamus, and
      cerebellum.

PMID- 17441841
TI  - MRI changes in thrombotic microangiopathy secondary to malignant hypertension.
AB  - Thrombotic microangiopathy with thrombocytopenia and intravascular hemolysis are
      characteristic of three disorders: malignant hypertension (MH), disseminated
      intravascular coagulation (DIC), and thrombocytopenic thrombotic purpura (TTP).
      We describe a patient with thrombotic microangiopathy secondary to malignant
      hypertension that caused extensive bilateral cortical ischemic infarction.

PMID- 17441842
TI  - Colloid cyst: diffusion MR imaging findings.
AB  - Colloid cysts usually have viscid gelatinous material or denser content. In an
      adult patient with a colloid cyst, diffusion magnetic resonance (MR) imaging was
      applied to detect its features with this sequence that if its viscous content may
      lead to a hyperintense appearance (decreased diffusion pattern) on b= 1000
      sec/mm(2) images similar to epidermoids. The colloid cyst had hypointense signal
      on the b= 1000 sec/mm(2) image. The ADC map had more information that the ADC
      value of the cyst was 1.58 x 10(-3) mm(2)/sec. This value was apparently higher
      than that of normal cerebral parenchyma, and was apparently lower than that of
      CSF. These diffusion MR imaging features of the colloid cyst are consistent with
      an elevated diffusion pattern in contrast to epidermoids.

PMID- 17441843
TI  - MR findings of intrathecal chemotherapy-related myelopathy in two cases: mimicker
      of subacute combined degeneration.
AB  - We report the findings of spinal magnetic resonance imaging (MRI) in 2 patients
      who had undergone intrathecal chemotherapy and presented with the subacute onset
      of ascending numbness and weakness. MRI revealed a symmetric hyperintensity at
      the posterior columns of the spinal cord from the lower cervical region down to
      the conus medullaris level on T2-weighted images, and no abnormal enhancement.
      The imaging findings are similar to those seen in subacute combined degeneration
      (SCD), but the serum vitamin B(12) levels were normal in these 2 cases.

PMID- 17441845
TI  - Oral tolerance to contact allergens: a common occurrence? A review.
AB  - Experimental and clinical oral tolerance to contact allergens has been reported
      sporadically, most notably in respect of nickel, and is generally assumed to be
      an uncommon phenomenon. There has recently been increased understanding of the
      immunological mechanisms inducing and maintaining oral tolerance. There are
      several contact allergens, including fragrance, antioxidant, and preservative
      chemicals, to which subjects are exposed through both cutaneous and oral routes.
      We examine the possibility that oral tolerance to contact allergens may be more
      common than previously thought. Animal models of oral tolerance to contact
      allergens indicate that cutaneous exposure to small, subsensitizing doses of
      contact allergens might negate any subsequent attempts to induce tolerance by
      oral administration. Extrapolating these observations to common human practises
      raises the possibility that application of contact allergens (fragrances,
      preservatives and antioxidants) in consumer products used by children could
      prevent or inhibit the later acquisition of specific tolerance resulting from
      'natural' dietary exposure after weaning. Existing data on formaldehyde may
      conflict with this theory, though this could be explained by allergen
      specificity. We propose that further work in this area is needed.

PMID- 17441846
TI  - Dose per unit area - a study of elicitation of nickel allergy.
AB  - BACKGROUND: Experimental sensitization depends upon the amount of allergen per
      unit skin area and is largely independent of the area size. OBJECTIVES: This
      study aimed at testing if this also applies for elicitation of nickel allergy.
      PATIENTS/METHODS: 20 nickel allergic individuals were tested with a patch test
      and a repeated open application test (ROAT). Nickel was applied on small and
      large areas. The varying parameters were area, total dose and dose per unit area.
      RESULTS: In the patch test, at a low concentration [15 microg nickel (microg
      Ni)/cm(2)], there were significantly higher scores on the large area with the
      same dose per area as the small area. At higher concentrations of nickel, no
      significant differences were found. In the ROAT at low concentration (6.64 microg
      Ni/cm(2)), it was found that the latency period until a reaction appeared was
      significantly shorter on the large area compared to the small area. It was also
      found that the ROAT threshold (per application) was lower than the patch test
      threshold. CONCLUSION: For elicitation of nickel allergy, the size of the exposed
      area and therefore the total amount of applied nickel, influence the elicitation
      reaction at some concentrations, even though the same dose per unit area is
      applied.

PMID- 17441847
TI  - Intermittent exposure to low-concentration paraphenylenediamine can be equivalent
      to single, higher-dose exposure.
AB  - Hair dye allergy is an important and increasingly common cause of allergic
      contact dermatitis. The role of repeated exposure in elicitation of allergy has
      not previously been extensively studied. We have therefore compared elicitation
      between single and intermittent exposure to paraphenylenediamine (PPD). 23
      subjects known to be allergic to PPD from positive patch tests were exposed to
      0.3% and 0.03% PPD, both in petrolatum and water, for 5 min at the same site
      every day for up to 8 D. In the same subjects, single exposures were also
      performed at different sites, from 5 to 40 min. Other experiments exposed rat
      skin to radiolabelled PPD as one-off application or multiple exposures. There
      were 8 reactions in the cumulative exposure site using 0.3% PPD in aqueous
      solution. In 7 of these, there was an exact correlation with reaction to the
      cumulative time needed for repeat exposures to elicit a reaction and the time
      needed for a reaction to the single exposure. There were no reactions to 0.03%
      PPD in water or pet under either type of exposure condition. There was also a
      positive correlation between grade of original reaction in clinic (+++, ++, +)
      and appearance/intensity of elicitation reactions. In the animal study,
      cumulative time and single exposure time sites correlated with regards to
      retention of radiolabelled substance within the skin. This study therefore
      demonstrates for the first time that, over the time period tested, the allergenic
      component of PPD accumulates in the skin. Hence, intermittent exposure to lower
      concentrations of PPD may be equivalent to higher concentration, one-off
      exposure.

PMID- 17441848
TI  - Is incident sensitization to p-phenylenediamine related to particular exposure
      patterns? Results of a questionnaire study.
AB  - Evidence regarding the risk of active sensitization (AS) to p-phenylenediamine
      (PPD), patch tested 1% in petrolatum, is conflicting. The objective of this study
      was to evaluate the relative frequency of 'environmental' exposures and skin
      reactions to products potentially containing PPD in subgroups of patients with
      versus without newly diagnosed contact allergy (CA) to PPD upon retesting.
      Patients patch tested twice with PPD between 1996 and 2004 in the Information
      Network of Departments of Dermatology (IVDK) network were identified and
      classified into 4 groups, according to the 2 test results with PPD at D3. A self
      administered questionnaire was mailed to 171 patients (response 57%). The
      frequency of exposure to 'henna tattoos', dark hair dyes, or textiles or work as
      hairdresser did not differ significantly between the groups. A significantly
      shorter median interval between the 2 patch tests was observed in the group with
      newly diagnosed PPD CA compared with the other groups (293 versus >700 days). The
      results of the study add new, if somewhat weak, evidence to the notion that patch
      testing with PPD may indeed carry some risk of AS, as environmental exposures to
      PPD were as common in the subgroup of patients with incident CA to PPD as in the
      remaining patients.

PMID- 17441849
TI  - Regional variability in stratum corneum reactivity to antiseptic formulations.
AB  - Skin does not react in an identical way to the action of chemicals over all
      anatomic sites. Accordingly, distinct regional differences have been described in
      relation to irritancy. The present study assesses the regional variations of
      stratum corneum (SC) reactivity to 3 proprietary antiseptic solutions (povidone
      iodine (PVP-I), 70 mg/ml and 100 mg/ml, and chlorhexidine digluconate 50 mg/ml)
      using the corneoxenometry (CXM) bioassay. SC was harvested from the volar
      forearm, the forehead and the back in 30 young adults. Each SC sample was covered
      by one of the neat test product or deionized water for 2 hr at 20 degrees C. The
      intrinsic staining property of each antiseptic on SC was assessed by reflectance
      colorimetry. For the CXM bioassay, samples were then stained by a toluidine blue
      basic fuschin solution in order to show protein denaturation induced by the test
      products. The colorimetric index of mildness (CIM = L*- Chroma C*) was measured
      by colorimetry. Data show that PVP-I 100 mg/ml was the least reactive antiseptic
      to the SC. It was significantly milder than the 2 other antiseptics.

PMID- 17441850
TI  - Airborne contact dermatitis in gaitas (flageolets) constructors after exposure to
      sawdust of caviuna.
AB  - Exotic wood species are used in the manufacture of furniture, musical
      instruments, tool handles, and other wooden items. Exposure to sawdust of the
      wood can produce dermatitis on exposed areas in woodworkers. We studied 7
      patients, gaitas constructors who used caviuna wood to make their instruments.
      They developed dermatitis on exposed areas hours after they had begun to work
      with caviuna. We performed patch tests using the European standard series,
      caviuna sawdust sample, and a series of dalbergiones. 15 controls were performed.
      Two caviuna samples provided by a patient were analysed by thin-layer
      chromatography (TLC). Patch test with caviuna sawdust yielded positive reactions
      in all patients. 5 of the 7 sufferers reacted strongly to obtusaquinine and (R)-4
      methoxydalbergione deriving from Dalbergia retusa, but also to sensitizers
      present in other rosewoods. Patch tests with R-3,4-dimethoxydalbergione deriving
      from Machaerium scleroxylum remained negative in the patients, as well as in
      control subjects. The TLC analysis of the samples showed that the woods could
      have been M. scleroxylum, D. cearensis or D. frustescens, but not D. retusa. In
      our patients, airborne contact dermatitis was caused by exposure to caviuna
      sawdust. The patients must have been in contact with different Dalbergia species
      and especially with D. retusa.

PMID- 17441851
TI  - Contact dermatitis to a rubber allergen with both dithiocarbamate and
      benzothiazole structure.
AB  - Contact dermatitis to rubber products are often caused by additives used during
      manufacture, and diagnosed from patch test with established rubber allergen
      series. In these series the compounds are divided into separate groups such as
      thiurams, dithiocarbamates and mercaptobenzothiazoles. The objectives were to
      investigate the substances with allergenic structures present in a diving mask
      giving rise to facial dermatitis, also those substances including structures from
      different groups of rubber chemicals. The rubber material was analysed by high
      performance liquid chromatography and diode-array detector. The patient was
      tested by epicutaneous tests using pure substances, extracts and authentic rubber
      material. 2-Benzothiazolyl-N,N-diethylthiocarbamylsulfide, was found in the
      diving mask and the patient showed positive reaction to the pure compound and to
      extracts of the diving mask. This compound has structures of both
      mercaptobenzothiazole and thiuram/dithiocarbamate in its formulae. Besides the
      established groups of rubber accelerators, uncommon allergens with structures
      from more than one group can be formed or added at vulcanization. Chemical
      analysis of the product is needed to find these allergens.

PMID- 17441852
TI  - Recommendation of appropriate amounts of petrolatum preparation to be applied at
      patch testing.
AB  - BACKGROUND: No recommendation exists on the amount of petrolatum (pet.)
      preparation to be applied in a Finn Chamber or van der Bend Chamber. OBJECTIVES:
      The aim of this study was to determine the appropriate amount of pet. preparation
      to apply in the Finn and van der Bend chambers. METHODS: 12 volunteers were patch
      tested with green-coloured pet. in Finn and van der Bend chambers on the back on
      3 occasions. Doses were 10, 15, 20, 25, and 30 mg initially and on second and
      third occasion, 10 mg was removed in van der Bend Chambers and 35 mg was added.
      On day 2, the test sites were scored. A negative test equalled a test area not
      covered to 100%. A positive test meant a completely green-coloured test area.
      Minor and major spreading was noted. The amount of pet. preparation yielding at
      most 5% negative reactions and having the least number of reactions with major
      spreading equalled the appropriate amount. RESULTS: For van der Bend Chambers,
      all doses yielded more than 5% negative reactions. For the Finn Chamber, 30, 25,
      and 20 mg pet. yielded less than 5% negative reactions and with major spreading
      in 60%, 40%, and 25% of test sites. CONCLUSIONS: 20 mg pet. preparation was the
      optimal dose for the Finn Chambers.

PMID- 17441853
TI  - Allergic contact dermatitis to guggul in a slimming cream.

PMID- 17441854
TI  - Allergic contact dermatitis to polyethylene glycol-7 hydrogenated castor oil.

PMID- 17441855
TI  - Delayed hypersensitivity to isopropyl alcohol.

PMID- 17441856
TI  - Allergic contact dermatitis from retinyl palmitate in polycaprolactone.

PMID- 17441857
TI  - Contact sensitivity to octyldodecanol and trometamol in an anti-itch cream.

PMID- 17441858
TI  - Multiple manifestations of chromate contact allergy.

PMID- 17441859
TI  - Allergic contact dermatitis to nickel in a hair clasp.

PMID- 17441860
TI  - Fixed drug eruption due to aceclofenac.

PMID- 17441861
TI  - Occupational allergic contact dermatitis from monoethanolamine in a dental nurse.

PMID- 17441862
TI  - Cheilitis due to Agaricus blazei Murill mushroom extract.

PMID- 17441863
TI  - Shoe dermatitis from para-tertiary butylphenol formaldehyde.

PMID- 17441864
TI  - Occupational contact allergy to cysteamine hydrochloride in permanent-wave
      solutions.

PMID- 17441865
TI  - Allergic contact dermatitis from luliconazole.

PMID- 17441866
TI  - Allergic contact dermatitis due to 1,3-butylene glycol and glycerol.

PMID- 17441867
TI  - Prolonged paresthesia due to sculptured acrylic nails.
AB  - Allergic reactions to acrylates in sculptured nails are common. However, there
      are few reports of paresthesia as a consequence of acrylic exposure, and such
      paresthesia does not necessarily accompany the evolution of the dermatitis.

PMID- 17441868
TI  - Effect of previous topical corticosteroid on patch testing.

PMID- 17441869
TI  - The link between patch testing and dental materials.

PMID- 17441871
TI  - Effects of pergolide on severe sleep bruxism in a patient experiencing oral
      implant failure.
AB  - In the patient described in this study, oral implants failed as a probable
      consequence of severe, polysomnographically confirmed sleep bruxism. As this
      patient had the wish to be re-implanted after this failure, we decided to try
      diminishing the frequency of bruxism and duration first. To that end, two
      management strategies were used. Their efficacy was evaluated
      polysomnographically, yielding a total of six overnight recordings. Of the
      selected management strategies, the administration of low doses of the dopamine
      D1/D2 receptor agonist pergolide finally resulted in a substantial and lasting
      reduction in the bruxism outcome measures under study. This result supports the
      previous suggestion that central neurochemicals like dopamine may be involved in
      the modulation of sleep bruxism. The case report also illustrates the importance
      of an extensive history taking (questionnaires as well as oral) and clinical
      examination of oral implant patients for the presence of severe bruxism before
      the implant procedure is started. In case of doubt, polysomnography may be
      considered to definitively confirm or rule out the presence of severe sleep
      bruxism.

PMID- 17441872
TI  - Frequency of parafunctional oral habits in patients with cerebral palsy.
AB  - Cerebral palsy (CP) is one of the most frequent conditions encountered in the
      daily practice of dentists who treat special-needs patients and it seems that
      parafunctional oral habits are often present in such individuals. The aim of this
      study was to investigate the frequency of occurrence of parafunctional habits in
      individuals with CP. Sixty-five patients with CP were evaluated through a
      questionnaire and clinical observation, regarding the following habits: pacifier
      sucking, finger-sucking, biting objects, tongue interposition, and bruxism. The
      results showed that nine (13.8%) patients presented with pacifier-sucking, four
      (6.1%) showed finger-sucking, 12 (18.4%) had the habit of biting objects, 27
      (41.5%) presented with tongue interposition, and 24 (36.9%) had eccentric
      bruxism. The significance of the presence of oral parafunctional habits in
      individuals with CP, revealed in this study, justifies the need to establish
      protocols for adequate prevention and clinical intervention in order to minimize
      the deleterious consequences that may result from such habits.

PMID- 17441873
TI  - Characteristics of a jaw reflex in humans with temporomandibular disorders: a
      preliminary report.
AB  - Electromyography was used to compare characteristics of an inhibitory jaw reflex
      in 10 temporomandibular disorder patients and 10 age- and sex-matched healthy
      controls. The methodology was novel in that the reflex was that evoked in the
      active masseter muscle, by electrical stimulation of perioral skin. This response
      has advantages over those previously studied as it avoids problems associated
      with stimulating in the moist intra-oral environment and it is monophasic, thus
      permitting easy quantification. The results have shown that (i) with the
      stimulation parameters employed, the reflex was present in all 10 control
      subjects, but in only eight of 10 temporomandibular disorder patients. (ii) When
      stimulation intensities were expressed as multiples of sensory threshold, there
      was no significant difference in the minimum level of stimulation required to
      evoke the reflex between the groups, although there was a trend for the patients
      with temporomandibular disorders to require higher intensities. (iii) Comparison
      of data from subjects giving responses at the same stimulus intensity (6 x
      sensory threshold: seven temporomandibular disorder patients, eight controls),
      showed no significant differences in the latencies or magnitudes of the reflex
      between the groups. However, the overall duration of the reflex was significantly
      shorter for the patients with temporomandibular disorders, with the reflex
      finishing significantly earlier. Thus even within the limitations of this study,
      it appears that an inhibitory jaw reflex evoked from stimulation around the
      mouth, may be weaker in temporomandibular disorder patients. This conclusion is
      consistent with previous studies on more complex jaw reflexes evoked by intra
      oral stimuli.

PMID- 17441874
TI  - A method for assessment of quality of life in relation to prosthodontics. Partial
      edentulism and removable partial dentures.
AB  - The aim of this study was to evaluate the possible use in prosthodontics of a
      method for an interview technique allowing maximal individuality within the
      cultural boundaries. The impact of partial edentulism and removable partial
      denture (RPD) wearing on quality of life was chosen as the target question. The
      interview included patient generated selection of five quality of life cues. The
      current status/intensity of each cue was measured by use of a Visual Analogue
      Scale (VAS), the relative weight/importance between the cues by a direct
      weighting (DW) instrument, and a summarized quality of life score was calculated.
      One hundred and one participants with partial edentulism with or without RPDs
      were included in the study. No correlation was found between the VAS- and DW
      scores, indicating that different aspects are measured with these two
      instruments. Sixty to seventy per cent of the participants answered positively to
      questions about the test method, including self-knowledge, consciousness and
      identification of needs and wishes. The 'Schedule for the Evaluation of
      Individual Quality of Life - Direct Weighting' turned out to be a useful
      instrument for assessing patients' priorities, and fulfils in many ways the
      demands for individualized problem identification, decision-making and treatment
      planning. The results of the comparison of RPD wearers and non-RPD wearers showed
      that aesthetics is a major factor and that the overall quality of life between
      the experienced RPD wearers and non-RPD wearers in this study did not differ
      significantly.

PMID- 17441875
TI  - Comparison of oral stereognosis in relation to age and the use of complete
      dentures.
AB  - The purpose of this study was to examine the age-related difference in oral
      sensory function by testing oral stereognostic ability (OSA) and to determine the
      effect of wearing complete dentures on OSA. Subjects were 20 dentate and 30
      edentulous elderly patients free from oral symptoms and pathologies, and 30
      younger dentate students as controls. The OSA tests were conducted with test
      pieces of 12 shaped forms. The duration time for recognition was noted and the
      answers were recorded using a three-point scale. anova and paired t-tests were
      used to examine significant differences. P-values <0.05 were considered to be
      statistically significant. The OSA score in older dentate participants and
      complete denture wearers was significantly higher than in younger dentate
      subjects. However, no significant difference was found in the OSA score between
      older dentate participants and complete denture wearers. When older edentulous
      subjects removed the maxillary and mandible complete dentures, the OSA score was
      significantly lower and the response time significantly longer than with
      dentures. Within the limitations of this study, an age-related difference in oral
      sensory function, as measured by OSA tests, was found. However, oral sensory
      function was not significantly different between fully dentate persons and
      complete denture wearers in the elderly.

PMID- 17441876
TI  - The prevalence of tooth discolouration and the self-satisfaction with tooth
      colour in a Chinese urban population.
AB  - OBJECTIVES: To determine the prevalence of tooth discolouration, self
      satisfaction with tooth colour, and correlation with socio-demographic
      behavioural factors in adults and teenagers in Chengdu, China. DESIGN: A cross
      sectional survey. PARTICIPANTS: 405 Chinese urban adults and teenagers from a
      multistage random probability sample. METHODS: Tooth colour was measured on the
      maxillary central incisors using a colorimeter. Tooth discolouration was
      determined according to the discolouration level figure and evaluation criteria.
      Self-satisfaction with tooth colour was assessed on a five-point qualitative
      scale. Data were coded and analyzed using SPSS software. RESULTS: The mean values
      for L*, a* and b* were 70.67 (s.d. 1.91), 4.29 (s.d. 2.05) and 17.51 (s.d. 4.13),
      respectively. Age and sex were the most important factors associated with tooth
      colour (P < 0.05). About half of the study population (48.9%) suffered from some
      tooth discolouration, and 52.6% were dissatisfied with their tooth colour.
      Education and smoking were significant factors affecting self-satisfaction with
      tooth colour (P < 0.05). CONCLUSIONS: Tooth discolouration is common among the
      Chinese, and many Chinese are dissatisfied with their tooth colour. Self
      satisfaction with tooth colour decreased with increasing severity of
      discolouration. Further research is needed to determine types of tooth
      discolouration among broader regions in China.

PMID- 17441877
TI  - The evaluation of direct composite restorations for the worn mandibular anterior
      dentition - clinical performance and patient satisfaction.
AB  - This prospective split-mouth clinical trial evaluated the performance and patient
      satisfaction of 168 Herculite XRV direct composite restorations bonded to the
      worn anterior dentition of 18 patients with localized anterior tooth surface
      loss. One hundred and six of these restorations were placed on the mandibular
      anterior teeth. The restorations increased the anterior occlusal vertical
      dimension between 0.5 and 5 mm and the posterior occlusal contacts were restored
      after a mean duration of 6.2 months (range: 3-13 months) in 14 out of the 15
      'Dahl' sub-group patients. The restorations were evaluated after 2.5 years of
      service by five examiners. Four patients and 23 mandibular restorations were lost
      to follow-up. Multiple clinical and restorative variables were assessed to
      determine their influence on restoration performance. Complete failure occurred
      in 6% of the restorations. Circumferential preparation and height of the
      restorative addition did not influence the performance of the restorations. A
      Visual Analogue Scale (VAS) was used to assess the patient's opinion regarding
      sensitivity, aesthetics, longevity and function of the worn mandibular anterior
      teeth. A statistically significant difference (95% CI) was found between the pre
      operative and 1-month review VAS responses for aesthetics and longevity and this
      was maintained at the 2.5-year review. Direct composite restorations placed at an
      increased occlusal vertical dimension are a simple and time-efficient method of
      managing the worn mandibular anterior dentition. Patient's acceptance and
      adaptation to the technique is good and the results are accompanied with a high
      level of patient satisfaction that is maintained for the medium-term.

PMID- 17441878
TI  - Analysis of early biofilm formation on oral implants in man.
AB  - Biofilm formation on oral implants can cause inflammation of peri-implant
      tissues, which endangers the long-term success of osseointegrated implants. It
      has been reported previously that implants revealing signs of peri-implantitis
      contain subgingival microbiota similar to those of natural teeth with
      periodontitis. The purpose of the first part of this study was an atraumatic,
      quantitative investigation of biofilm formation on oral implant abutments; the
      objective of the second part was to investigate whether Haemophilus
      actinomycetemcomitans and Porphyromonas gingivalis were present in the crevicular
      fluid around oral implants. Biofilm formation on 14 healing abutments, inserted
      for 14 days in 10 patients, was analysed quantitatively by use of secondary
      electron and Rutherford-backscattering-detection methods. A 16S rRNA-based
      polymerase chain reaction detection method was used to detect the presence of H.
      actinomycetemcomitans and P. gingivalis in the crevicular fluid. For this
      investigation, samples of sulcus fluid were collected with sterile paper points
      at four measurement points per abutment. The difference between biofilm coverage
      of supragingival surfaces (17.5 +/- 18.3%) and subgingival surfaces (0.8 +/-
      1.0%) was statistically significant (P < 0.05). By use of universal primers,
      bacteria were found in all the samples taken, although the two periodontal
      pathogens were not found in any of the samples. The absence of periodontal
      pathogens from the sulcus fluid during initial bacterial colonization, despite
      massive supragingival biofilm formation, substantiates the assumption that
      cellular adherence of peri-implant tissue by means of hemidesmosoma, actin
      filaments and microvilli reduces the risk of formation of anaerobic subgingival
      pockets.

PMID- 17441879
TI  - Phase transitions of silver and silver-palladium alloys immersed in mercury.
AB  - A series of Ag-Hg and Ag-Pd-Hg phases have been prepared by immersion in mercury
      and subsequent heat treatment of pure Ag and a series of Ag-Pd alloys. Phase
      transitions, along with the changes involved in morphology and chemistry, are
      investigated. Experimental results indicate that when mercury-immersed Ag discs
      are heat-treated at 90 degrees C for 12 h, large (>50 microm) crystals with Ag/Hg
      atomic ratios close to those of stoichiometric AgHg(2) form on the Ag surface.
      Heat treatment for 36 h causes these crystals to disintegrate into smaller
      (majority <10 microm) Ag(2)Hg(3) (gamma(1)) crystals. After 60 h, the
      stoichiometric gamma(1) crystals further breakdown into even smaller
      stoichiometric AgHg(beta(1)) crystals. The oft-referenced beta(1) phase
      Ag(1.1)Hg(0.9) is not supported in the present study. Addition of Pd to Ag has a
      dramatic effect on the morphology of the gamma(1) phase. With more addition of
      Pd, large-faceted and elongated gamma(1) crystals tend to grow in the midst of
      smaller matrix gamma(1) crystals. All three different Pd-containing crystals have
      (Ag + Pd)/Hg ratios very close to those of the stoichiometric gamma(1) phase,
      indicating that added Pd tends to replace Ag, rather than Hg, in the gamma(1)
      phase.

PMID- 17441880
TI  - A biocompatibility study of a reinforced acrylic-based hybrid denture composite
      resin with polyhedraloligosilsesquioxane.
AB  - Acrylic-based denture materials have several common weak points, such as
      shrinkage after curing, lack of strength and toxicity. In order to solve these
      problems, we adapted a hybrid system using acrylic polymer and
      polyhedraloligosilsesquioxane (POSS). The aim of the study was to investigate the
      biocompatibility of a reinforced acrylic-based hybrid denture composite resin
      with POSS. Specimens of a novel polymeric denture base resin, in which POSS was
      used to partially replace the commonly used base monomer, were fabricated. In
      order to examine changes in biocompatibility with time, fresh specimens, along
      with specimens soaked in distilled water for 24 and 72 h were fabricated. Three
      other types of acrylic denture base resins were used to prepare the resin
      specimens. Biocompatibility (as measured by a metabolic assay, an agar overlay
      test, and a mutagenesis assay) of the composites was tested. The metabolic and
      mutagenesis assays were conducted with pure culture medium as a control. In this
      study, the reinforced acrylic-based hybrid denture composite resin with POSS
      showed improved biocompatibility and lower mutagenicity than the control.
      Statistical examinations showed the cell metabolic activity of the novel
      polymeric denture base resin in the 72-h immersion case as having almost the same
      inclination as the control. We hope that these results might aid in the
      development of a reinforced acrylic-based denture resin.

PMID- 17441881
TI  - Immune concept of human papillomaviruses and related antigens in local cancer
      milieu of human cervical neoplasia.
AB  - It is presently the right time for clarifying human papillomavirus (HPV)
      associated cellular immunity and clinical implications before global HPV
      vaccination programs begin. Infection with oncogenic HPV associates with the
      progression of cervical neoplasia. Both cellular and humoral immune responses are
      essential for the clearance of HPV-associated cervical lesions. There is
      increasing evidence that the immune system plays a pivotal role in determining
      the outcome of HPV infection. Viruses and associated neoplastic cells are
      proposed to have evolved mechanisms to avoid immune attack. T-cell-mediated
      immune responses against oncogenic HPV are believed to play a central role in
      cervical carcinogenesis. The presence of HPV-specific cytotoxic T lymphocytes
      (CTL) in a majority of human cervical cancer patients provides an approach for
      further study of their functional role in modulating this malignancy. Tumor
      infiltrating lymphocytes (TIL) develop as manifestations of the recognition and
      defense against malignant cells by the host immune system. Cancer cells may
      overcome immune surveillance, either by downregulating the proliferation of HPV
      specific CTL, or altering the effector compositions of immune cells against HPV
      infections. TIL in the tumor microenvironment can be functionally inhibited and
      lose the ability of clonal proliferation as a result of depressed expression of
      IL-2Ralpha. The upregulation of inhibitory signaling relates to the modulation of
      the virus- and/or tumor-specific immune responses. Alteration of host genetic
      susceptibility may also lead to abnormal immune response as a general genomic
      instability resulting from virus persistence. Induction of HPV-specific immune
      responses is anticipated as an intimate point for the treatment of cervical
      neoplasia.

PMID- 17441882
TI  - Hemodynamic vulnerability to acute hypoxia in day 10.5-16.5 murine embryos.
AB  - AIM: We tested the hypothesis that murine embryonic cardiovascular (CV) function
      is vulnerable to transient changes in maternal transplacental oxygen support
      during the critical period of CV morphogenesis. METHODS: We measured maternal
      heart rate (MHR), maternal blood pressure (MBP), and embryonic heart rate (EHR)
      during mechanical ventilatory support, then induced transient maternal hypoxia
      daily from gestation day (ED) 10.5 to ED16.5 in pregnant ICR mice. Hypoxia was
      induced by suspending mechanical ventilation for 30 s or by the replacement of
      inspired oxygen with nitrogen (75% or 100%) for 30 s while maintaining
      ventilation. RESULTS: We noted a rapid onset of maternal hypotension in response
      to hypoxia that quickly recovered following reoxygenation. Following a brief lag
      time that was not gestation specific, EHR decreased in response to hypoxia. The
      magnitude of embryo bradycardia and the rate of EHR decline and recovery
      displayed gestation specific patterns. The magnitude of embryo bradycardia was
      similar from ED10.5 to ED13.5 and then increased with gestation. Before ED13.5,
      only 40% of embryos recovered to the baseline EHR following transient maternal
      hypoxia (vs 80% of embryos after ED 13.5). EHR following recovery exceeded
      baseline EHR after ED15.5. Nitrogen inhalation (75% or 100%) produced changes in
      maternal and embryonic hemodynamics similar to suspended ventilation induced
      hypoxia. CONCLUSIONS: The mammalian embryo is vulnerable to transient decreases
      in maternal oxygenation during the critical period of organogenesis and the
      gestational specific EHR response to hypoxia may reflect both increased embryonic
      oxygen demand and the maturation of neurohumoral heart rate regulation.

PMID- 17441883
TI  - Effect of vitrification method on survivability, follicular growth and ovulation
      of preantral follicles in mice.
AB  - AIM: This study was designed to compare the survival rates, follicular growth
      rates, and ovulation rates of vitrified preantral follicles (PF) from ovaries
      with those isolated from a vitrified ovarian cortical strip. METHODS: Mouse
      ovaries were divided into three groups: those not treated by vitrification of the
      PF (control), those treated by vitrification of the PF isolated from the ovaries
      (group I), and those treated by vitrification of ovarian tissue followed by PF
      isolation (group II). The group I samples were exposed to equilibration solution
      (EG-20) for 5.0 min plus vitrification solution (EFS-40) for 0.5 min, while the
      group II samples were exposed to EG-20 for 10.0 min plus EFS-40 for 2.0 min,
      before vitrification. They were subsequently placed on an electron microscope
      grid, and submerged immediately in liquid nitrogen. After thawing, the survival
      rate and the growth rate of the follicles were evaluated every 2 days. RESULTS:
      In the in vitro condition, the follicles grew and developed into antral follicles
      in groups I and II. The survival rate of the group I samples was higher than that
      of the group II samples during the in vitro culture (P<0.05). The growth rates of
      the follicles in group I were higher than those in group II after day 6 (P<0.05).
      The ovulation rate of the samples in group I was higher than that of group II
      (P<0.05). CONCLUSION: These results demonstrated that direct PF vitrification
      appeared to be better than vitrification of the PF isolated from ovarian tissue.

PMID- 17441884
TI  - Comparative study of transperineal and transabdominal sonography in the diagnosis
      of placenta previa.
AB  - AIM: To assess the role of transperineal sonography (TPS) in the diagnosis of
      placenta previa in the third trimester and to compare it with transabdominal
      sonography (TAS). METHODS: Seventy-five suspected cases of placenta previa were
      subjected to TAS with half full bladder and to the TPS with empty bladder to
      visualize the inner surface of the cervix and inferior edge of the placenta. The
      presence or absence of placenta previa was confirmed at delivery. RESULTS: TAS
      depicted the inferior edge of placenta in 98.7% of cases compared to 96% with
      TPS. Internal cervical os was visualized in 98.7% with TAS compared to 100% with
      TPS. Placenta previa was confirmed at delivery in 74 cases with one false
      positive in TPS, six false positive in TAS. The positive predictive value (PPV)
      value in the diagnosis of placenta previa was 92% with TAS compared to 98.6% with
      TPS. Accuracy of TPS in diagnosing placenta previa was 98.7%. PPV in the
      diagnosis of minor degree placenta previa was less 86.36% with TAS compared to
      TPS 100% though for major degree both are in agreement. CONCLUSION: TPS is a
      valuable procedure to compliment TAS in the diagnosis of placenta previa and
      helps to exclude false positive and to determine the mode of delivery, although
      it cannot replace TAS.

PMID- 17441885
TI  - Ionized and total magnesium concentration in patients with severe preeclampsia
      eclampsia undergoing magnesium sulfate therapy.
AB  - AIM: As ionized magnesium is the active form of magnesium and exerts a
      therapeutic effect, the present study was performed to determine the levels and
      correlations between ionized and total magnesium under baseline and therapeutic
      conditions in patients with severe preeclampsia and eclampsia receiving magnesium
      sulfate. METHODS: Fifty singleton patients with severe preeclampsia received a
      loading dose of 4 g of magnesium sulfate, followed by 2 g per hour as maintenance
      dose until 24 h after delivery, or 24 h after the last seizure in case of
      postpartum convulsions. Serial blood samples were taken before magnesium sulfate
      infusion, 30 min and 240 min after the initiation of the infusion and 4 h after
      the discontinuation of the drug. Data were analyzed by repeated measure ANOVA and
      paired t-test. RESULTS: Baseline levels of total and ionized magnesium were 2.4+/
      0.6 mEq/L and 1.3+/-0.5 mEq/L (mean+/-SD), respectively. Putative level of 4
      mEq/L of total magnesium was not obtained in up to 42% of patients during the
      treatment. There was not any significant correlation between the two forms of
      magnesium under baseline and therapeutic conditions. CONCLUSION: Despite the
      effectiveness of the standard regimen of magnesium sulfate in the treatment and
      prevention of eclamptic seizures, it can not provide the proposed therapeutic
      level of magnesium in all patients. With respect to the lack of correlation
      between ionized and total magnesium, further studies are necessary to investigate
      the superiority of measurement of ionized, rather than total magnesium, for
      titration of therapeutic magnesium sulfate infusion.

PMID- 17441886
TI  - Cord blood cortisol level is lower in growth-restricted newborns.
AB  - AIM: To establish the difference in plasma cortisol concentrations between
      newborns with intrauterine growth-restricted (IUGR) and appropriate for
      gestational age (AGA) birthweights. SUBJECTS AND METHODS: We measured plasma
      cortisol concentrations in the umbilical venous cord blood of 68 IUGR newborns
      and 71 AGA birthweight newborns. All newborns were delivered in term, vaginally,
      in the morning, within 8 hours and had APGAR scores greater or equal to eight.
      RESULTS: There was no significant difference between compared groups according to
      maternal age, parity, gestational age and neonatal gender. Neonatal plasma
      cortisol levels were significantly lower in the IUGR (median: 312.3 mmol/L, min
      max: 158.9-588.1 mmol/L) compared to the AGA group (median: 458.7 mmol/L, min
      max: 314.5-718.5 mmol/L) (Mann-Whitney U-test; P<0000). The probability of having
      a cortisol plasma level greater than or equal to 458.7 mmol/L for IUGR newborns
      was only 1:12, and to have cortisol plasma level less than or equal to 312.3
      mmol/L for AGA newborns was much lower (0:34). In the range of plasma cortisol
      level between 312.3 mmol/L and 458.7 mmol/L, no statistically significant
      difference in the plasma cortisol level between IUGR and AGA newborns was found.
      CONCLUSIONS: Neonatal plasma cortisol level is lower in the IUGR compared to the
      AGA group. Our results suggest that endocrine relationships seem to be lost in a
      specific group of the IUGR newborns. Although we usually tend to simplify the
      problem and declare only one cause, this time it is impossible. It is probable
      that the cause is hidden in small and insufficient placenta with deranged auto
      regulation of placental 11beta-HSD-2 mechanism.

PMID- 17441887
TI  - Effect of maternal fasting on uterine arterial blood flow.
AB  - AIM: To determine the effect maternal diet pattern on the uterine artery Doppler
      flow velocimetry. METHODS: This is a cross-sectional observational study. The
      uterine artery Doppler flow velocimetry was measured between 20 and 24 weeks'
      gestation in healthy pregnant women observing Ramadan. For each fasting mother, a
      non-fasting healthy pregnant woman was recruited as a control. Maternal blood
      glucose level was measured. RESULTS: A total of 106 pregnant women were studied.
      The mean hours since last oral intake were significantly longer, and the maternal
      glucose level was significantly lower in the study group than in the control
      group. The Mean (95% CI) of the uterine artery pulsatility index, resistance
      index, peak systolic velocity, end diastolic velocity and systolic/diastolic
      ratio was similar in both groups. CONCLUSION: Maternal fasting is not associated
      with significant changes in the uterine artery Doppler flow velocimetry.

PMID- 17441888
TI  - Matrix metalloproteinase-1 promoter polymorphism and epithelial ovarian cancer:
      does ethnicity matter?
AB  - AIM: To estimate the relationship between matrix metalloproteinase (MMP)-1
      promoter -1607 bp polymorphism and the risk of epithelial ovarian cancer (EOC) in
      Korean women and to clarify the ethnic difference in genotype distribution of
      this polymorphism. METHODS: Single nucleotide polymorphism (SNP) of MMP-1
      promoter -1607 region in 133 EOC patients and 332 cancer-free patients were
      investigated. Then the associations of this polymorphism with EOC or its
      clinicopathological parameters were analyzed. In addition, genotype distributions
      of this polymorphism in Korean women were compared with those of other races by
      extracting data from the previously published literature. RESULTS: We found no
      relationship between MMP-1 promoter -1607 bp polymorphism and epithelial ovarian
      cancer in a Korean population. Furthermore, we found ethnicity-dependent
      differences in genotype distributions and allele frequencies by comparison with
      previous articles on this topic. We report significant ethnic differences in the
      genotype distributions and allele frequencies of the MMP-1 promoter -1607 bp
      polymorphism. CONCLUSION: Our results indicate that MMP-1-1607 bp polymorphism
      shows ethnic diversity, and that the hypothesis that this polymorphism is
      associated with epithelial ovarian cancer is not supported by this study in a
      Korean population. Moreover, this finding concurs with results obtained in white
      Americans and Europeans.

PMID- 17441889
TI  - Comparison of midline and Pfannenstiel incision for radical hysterectomy with
      pelvic and paraaortic lymphadenectomy in cervical carcinoma.
AB  - AIM: To compare Pfannenstiel and midline incisions with respect to efficacy and
      early postoperative surgical site complications in patients with early stage
      cervical carcinoma. METHODS: Patients with cervical carcinoma who underwent
      radical hysterectomy during 1995-2004 are retrospectively reviewed. There were 40
      patients in the Pfannenstiel group and 71 patients in the midline group.
      Patients' age, type of incision, operative time, hospitalization length,
      postoperative surgical site complications, pre and postoperative Hb levels,
      number of extracted pelvic and paraaortic lymph nodes were the variables
      collected from the patients' files and oncology follow-up forms. RESULTS: Mean
      age (53.5+/-6.96 vs 55.9+/-10.5, P=0.2) and preoperative Hb levels of patients
      (12.52+/-1.48 vs 12.94+/-1.34, P=0.17) were not statistically different in
      midline and Pfannenstiel groups, respectively. Operative time (141.8+/-36 vs
      135.8+/-31 min), number of extracted lymph nodes in pelvic (23.05+/-9.7 vs 23.5+/
      8.07) and paraaortic areas (3.17+/-1.68 vs 2.66+/-1.15) were not significantly
      different among the midline and Pfannenstiel groups, respectively (P>0.05).
      Although postoperative incisional complications were more common in the midline
      group, this difference did not reach a significant level (11.3% vs 7.5%, P=0.52).
      Duration of hospitalization was not significantly different between the midline
      and Pfannenstiel groups, respectively (6.3+/-2.69 vs 6.2+/-2.72 days, P=0.21).
      Multivariate analysis revealed postoperative Hb levels to be significantly
      different among the groups (P=0.017, OR=1.59, 95% CI: 1.08-2.35). CONCLUSION:
      Pfannenstiel incision can be used for radical hysterectomy with pelvic and
      paraaortic lymphadenectomy in selected patients with cervical carcinoma, without
      any negative influence on optimal resectability of tumor and surgical morbidity.

PMID- 17441890
TI  - Is prostate-specific antigen a potential new marker of androgen excess in
      polycystic ovary syndrome?
AB  - AIM: To determine whether serum prostate-specific antigen (PSA) levels are
      increased in polycystic ovary syndrome (PCOS) and the possibility of PSA to be
      used as a diagnostic marker of hyperandrogenism in females. METHODS: A total of
      43 women with PCOS and 43 age-matched healthy females were recruited in this
      prospective case-control study. The subjects were compared by means of
      demographic parameters, hormonal and metabolic measures and serum PSA levels. The
      correlations between this marker and a wide variety of hormonal, biochemical,
      anthropometric measures were evaluated. Student's t-test, chi2-test and
      Spearman's correlation analysis were used for the statistical analysis where
      appropriate. Statistical significance was assumed with a value of P<0.05.
      RESULTS: Mean body mass index, waist/hip ratio, Ferriman-Gallwey scores (FG),
      lutenizing hormone/follicle stimulating hormone ratio, insulin resistance, serum
      triglycerides and very low density lipoprotein levels were demonstrated to be
      significantly higher in PCOS (P=0.02, P=0.008, P<or=0.001, P<or=0.001, P=0.007,
      P<or=0.001, P=0.01, respectively). Total testosterone (TT),
      dehydroepiandrosteronesulfate (DHEAS) levels appeared to be significantly higher
      in PCOS (P=0.002, P<or=0.001, respectively). Serum PSA levels were found to be
      significantly higher in PCOS (PSA: 0.026+/-0.023 ng/mL in PCOS, PSA: 0.009+/
      0.008 ng/mL in control cases, P<0.001). Sex hormone binding globulin (SHBG) was
      significantly lower in the subjects with PCOS (P<0.001). Additionally, positive
      correlations between PSA and FG scores (r: 0.417, P<or=0.001), PSA and TT (r:
      0.456, P=0.03) and between PSA and DHEAS (r: 0.268, P=0.02) were found. A
      negative correlation between SHBG and PSA was apparent (r: -0.40, P=0.04).
      CONCLUSION: PSA is a well-established tumor marker of prostatic adenocarcinoma.
      It is also shown to be produced by extraprostatic tissues and fluids. As the gene
      expression of PSA is upregulated by the androgens and progestins in hormonally
      responsive tissues, hyperandrogenic syndromes such as PCOS may be associated with
      elevated serum PSA levels. PSA appears to be a promising marker of endogenous
      androgen excess in females suffering from PCOS.

PMID- 17441891
TI  - Efficacy of laparoscopic ovarian drilling for polycystic ovary syndrome resistant
      to clomiphene citrate.
AB  - AIM: It is difficult to induce ovulation in patients with polycystic ovary
      syndrome (PCOS) resistant to clomiphene citrate (CC) because of the narrow safety
      margin of human menopausal gonadotropin preparations. In the present study,
      patients diagnosed as having PCOS according to the Japanese diagnostic criteria
      were divided into two groups (Groups H and N). Testosterone level was used as a
      cut-off value between Groups H and N to examine the usefulness of laparoscopic
      ovarian drilling (LOD) to induce ovulation. METHODS: Thirty-two women with PCOS
      resistant to CC who underwent LOD were evaluated. The patients were divided into
      a high and a normal androgen group (Groups H and N with 19 and 13 patients,
      respectively) based on the level of testosterone measured 1 week before surgery
      using a cut-off value of 50 ng/dL. LOD was performed with microlaparoscopy under
      intravenous anesthesia. RESULTS: After LOD, spontaneous ovulation occurred in 16
      (84.2%) and nine (69.2%) patients in Groups H and N, respectively. Additional
      treatment with CC was given to 12 (63.2%) and 11 (84.6%) patients, respectively.
      No significant difference was noted with regard to the spontaneous ovulation rate
      after LOD. Eighteen pregnancies were established in 17 patients (53.1%). The
      pregnancy rate after LOD was not significantly different between Groups H and N:
      42.1% (8 patients) and 76.9% (10 patients), respectively. CONCLUSION: Patients
      with PCOS as diagnosed based on the Japanese diagnostic criteria include those
      with increased and normal androgen levels. LOD is considered an effective
      ovulation induction method for both types of patients with PCOS.

PMID- 17441892
TI  - How does a concomitant surgery effect the outcomes of Burch colposuspension?
AB  - AIM: To evaluate the outcomes of 90 Burch colposuspension procedures with or
      without concomitant surgery after a 6-year follow-up period. METHODS: The study
      was carried out in the urogynecology department of Ankara Etlik Women's and
      Maternity Teaching Hospital, Turkey. Ninety women who were diagnosed as having
      genuine stress urinary incontinence (GSI) were enrolled in this study. The Burch
      colposuspension procedure was performed for the treatment of genuine stress
      urinary incontinence with or without a concomitant surgery RESULTS: After a 6
      year follow-up, it has been noted that concomitant surgeries have no effect on
      the outcome of continence (P>0.05). Pelvic prolapse incidence was 7%. No voiding
      difficulty was observed. CONCLUSION: The study shows that concomitant surgeries
      have no effect on the outcome of continence. However, concomitant surgery can
      increase operational morbidity. Modified McCall culdoplasty does not seem to be a
      preventive measure for pelvic organ prolapse.

PMID- 17441893
TI  - Severe, gestational, non-familial, non-genetic hypertriglyceridemia.
AB  - Severe hypertriglyceridemia is a rare condition in pregnancy. All the cases of
      severe gestational hypertriglyceridemia that have been reported previously in the
      literature were caused by genetic mutations or familial hypertriglyceridemia
      secondary to lipoprotein lipase deficiency or apolipoprotein C-II deficiency. We
      report the first case of severe, non-genetic, non-familial, pregnancy-induced
      hypertriglyceridemia. The genetic underlying causes were excluded by molecular
      genetic investigation. The reported case was managed solely by strict dietary
      control. Hypertriglyceridemia was diagnosed incidentally during pregnancy, in
      this case, while taking a blood sample to check her hemoglobin level. Acute
      pancreatitis, which is a relatively common life threatening complication of this
      condition, was avoided. This report reviews the subtypes of hyperlipidemia,
      clinical picture, antenatal management and its effect on pregnancy and vice
      versa. It is important that the clinician has a clear understanding of the normal
      lipid profile during pregnancy, the clinical picture, the potential
      complications, available treatment options of hypertriglyceridemia particularly
      during pregnancy. The timing and route of delivery should be individualized.

PMID- 17441894
TI  - Angiographic uterine artery embolization followed by immediate curettage: an
      efficient treatment for controlling heavy bleeding and avoiding recurrent
      bleeding in cervical pregnancy.
AB  - Two cases of cervical pregnancy with heavy bleeding successfully treated by
      uterine artery embolization (UAE) followed by immediate curettage are described
      in this report. Case 1 demonstrated intermittent bleeding after serious bleeding
      was successfully controlled by UAE. Serum beta human chorionic gonadotropin (beta
      hCG) level rose remarkably after a short time decline. Transvaginal sonography
      consistently revealed a heterogeneous mass in the cervix. Repeated UAE followed
      by immediate curettage was performed and complete resolution was achieved. Case 2
      was also successfully managed by UAE followed by immediate curettage after
      failure of medical treatment. This report suggests that UAE followed by immediate
      curettage is a safe and efficient procedure for controlling heavy bleeding and
      avoiding recurrent bleeding when fertility capacity is desired in cases of
      cervical pregnancy with fetal cardiac activity and high beta-hCG concentration.

PMID- 17441895
TI  - Mother with post-partum group B Streptococcus meningitis and cerebellar abscess.
AB  - We report the case of a 25-year-old Malay woman, admitted for preterm delivery at
      35 weeks' gestation. Vaginal swab did not isolate any organism. She delivered a
      baby girl who developed respiratory distress syndrome, requiring ventilation.
      Although chest radiograph showed hyaline membrane disease with pneumonia, septic
      workout was negative. The mother was discharged on the next day. Seven days
      postpartum, the mother presented with fever and fits and was diagnosed to have
      meningo-encephalitis. Lumbar puncture isolated group B Streptococcus (GBS) and
      MRI revealed a superior cerebellar abscess. She was treated and survived the
      episode. This case illustrates the uncommon situation where GBS infection was
      confirmed via maternal septic workout rather than neonatal, although both
      presented with severe disease.

PMID- 17441896
TI  - Synchronous rectal and colon cancer caused by familial polyposis coli during
      pregnancy.
AB  - The management of colon and rectal cancer during pregnancy is controversial and
      challenging. Rectal or colon cancer during pregnancy is a very rare event. A 29
      year-old woman, pregnant with her second child, was diagnosed with rectal cancer
      causing bowel obstruction and synchronous colon cancer during the 27th week of
      gestation. Both cancers occurred as a result of familial polyposis. This is the
      first case of synchronous rectal and colon cancer caused by familial polyposis
      during pregnancy reported in the published literature. We discuss the therapeutic
      interventions and the surgical management of the cancer in relation to the
      gestation.

PMID- 17441897
TI  - A case of pulmonary type of ovarian small cell carcinoma.
AB  - Small cell carcinoma is a rare form of ovarian cancer with a poor prognosis. It
      is divided into two types, the hypercalcemic and the pulmonary type, of which the
      latter is extremely rare. A 49-year-old woman presented with an acute abdomen and
      was suspected to have torsion of a left ovarian tumor, which was followed up with
      an emergency operation. Postoperative pathological examination gave a diagnosis
      of the pulmonary type of ovarian small cell carcinoma. Six courses of paclitaxel
      and carboplatin therapy were given as adjuvant chemotherapy. The patient has
      survived for 36 months without recurrence. Here we present an extremely rare
      patient with the pulmonary type of ovarian small cell carcinoma.

PMID- 17441898
TI  - Clinical pitfalls of pain recurrence in endometriosis arising in the posterior
      vaginal fornix.
AB  - Endometriotic nodules in the lower genital tract often cause dysmenorrhea and
      dyspareunia. We report here a case of posterior vaginal fornix endometriosis that
      was overlooked for several years. We performed a trans-vaginal resection after
      the associated pain was not relieved by repetitive gonadotropin-releasing hormone
      agonist (GnRHa) therapy or abdominal surgery. After the resection, the patient's
      symptoms disappeared. The patient subsequently conceived and proceeded to a full
      term delivery. The pathological diagnosis was 'endometriosis of the vagina.'
      Immunohistochemical staining revealed that the progesterone receptor-positive
      cells outnumbered the estrogen receptor-positive cells. We emphasize that the
      existence of vaginal lesions should be considered in cases in which pain has not
      improved despite long-term GnRHa administration, or in cases involving
      dyspareunia. To provide appropriate treatment, attentive evaluation and careful
      examination of the disease are necessary for a patient with prolonged
      unsatisfactory progress.

PMID- 17441899
TI  - Appendiceal adenocarcinoma presenting with bilateral Krukenberg tumors.
AB  - Primary appendiceal malignancy metastatic to the ovaries is a condition that may
      mimic advanced stage ovarian cancer. This condition is rarely diagnosed
      preoperatively. A 52-year-old woman referred to our institution for presumed
      advanced stage of ovarian cancer was found to have primary appendiceal
      adenocarcinoma metastatic to ovaries at laparotomy. We describe the clinical
      course of the patient. It is important for the gynecologist-oncologist to include
      tumors of the appendix into the differential diagnosis of any case of ovarian
      tumor.

PMID- 17441900
TI  - Isolated torsion of fallopian tube in a premenarcheal 12-year-old girl.
AB  - Isolated torsion of fallopian tubes should be considered even at premenarcheal
      ages in cases of acute pelvic pain, and prompt surgery can preserve the tube and
      thus fertility. It is an uncommon emergency event and a difficult condition to
      evaluate clinically. This report focuses on a 12-year-old premenarcheal girl who
      presented with acute pelvic pain of 2 days. Pelvic ultrasound showed an adnexal
      mass on the left side. Laparoscopy was performed and an isolated tubal torsion
      was discovered. The tube was necrotic and salpingectomy was performed. The
      appendix appeared to be hyperemic and erectile. Appendectomy was also performed
      to rule out appendicitis. It's our recommendation that in the differential
      diagnosis of acute lower abdominal pain of girls, isolated torsion of the
      fallopian tubes should be considered. Also, preservation of the tube and
      fertility should be possible with prompt surgical intervention.

PMID- 17441901
TI  - Paclitaxel and carboplatin for large cell neuroendocrine carcinoma of the uterine
      cervix.
AB  - The prognosis of large cell neuroendocrine carcinoma (LCNEC) of the uterine
      cervix is generally poor despite multimodality of treatments. We report a case of
      advanced stage cervical LCNEC that showed definite response to
      paclitaxel/carboplatin, resulting in years of survival. The patient was referred
      to our institution after undergoing a simple hysterectomy with bilateral salpingo
      oophorectomy in her local hospital because of a ruptured metastatic ovarian mass.
      She declined pelvic radiation treatment, so adjuvant chemotherapy (six cycles of
      paclitaxel/carboplatin) was given for the residual pelvic nodal diseases.
      Clinical complete remission was obtained, with a disease-free period of 19
      months. Systemic recurrent diseases also showed partial response to the same drug
      regimen for months with only minimal toxicity. However, she subsequently had
      progressive diseases in the liver and brain and finally died at 44 months after
      primary diagnosis and 19 months after recurrent diseases.

PMID- 17441902
TI  - Molecular modeling suggests conformational scaffolds specifically targeting five
      subtypes of somatostatin receptors.
AB  - Several analogs of somatostatin with conformational constraints in their peptide
      backbones have been modeled to determine energetically feasible conformations.
      Comparison of low-energy backbone structures of these peptides suggested unique
      conformations of the central Phe/Ala(i)-D-Trp(i+1)-Lys(i+2)-Thr(i+3) fragment
      characteristic for specific interactions of somatostatin with each of the five
      distinct subtypes of somatostatin receptors (SSTRs). The conformations obtained
      were in good agreement with experimental data obtained earlier by NMR
      measurements and/or X-ray crystallography. The results help rationalize
      experimental observations on the specificity of binding of various somatostatin
      analogs with different subtypes of the SSTRs. They also serve as templates for
      the design of conformationally constrained non-peptide scaffolds that effectively
      and selectively interact with different subtypes of SSTRs. Such scaffolds can be
      convenient carriers of radiolabels and near-infrared labels in specific agents
      for imaging tumors expressing different SSTR subtypes.

PMID- 17441903
TI  - Synthesis of peptidyl ene diones: selective inactivators of the cysteine
      proteinases.
AB  - A series of synthetic peptides in which the C-terminal carboxyl grouping (
      CO(2)H) of each has been chemically converted into a variety of ene dione
      derivatives (-CO-CH=CH-CO-X; X = -H, -Me, -OBut, -OEt, -OMe, -CO-OMe), have been
      prepared and tested as inactivators against typical members of the serine and
      cysteine protease families. For example, the sequences Cbz-Pro-Phe-CH=CH-CO-OEt
      (I) which fulfils the known primary and secondary specificity requirements of the
      serine protease chymotrypsin, and Cbz-Phe-Ala-CH=CH-CO-OEt (II) which represents
      a general recognition sequence for cysteine proteases such as cathepsins B, L and
      S, have been tested as putative irreversible inactivators of their respective
      target proteases. It was found that, whereas II, for example, functioned as a
      time-dependent, irreversible inactivator of each of the cysteine proteases, I
      behaved only as a modest competitive reversible inhibitor of chymotrypsin. Within
      the simple ester sequences Cbz-Phe-Ala-CH=CH-CO-R, the rank order of inhibitor
      effectiveness decreases in the order R = -OMe > -OEt >> -OBut. It was also found
      that the presence of both an unsaturated double bond and an ester (or alpha-keto
      ester) moiety were indispensable for obtaining irreversible inactivators. Of the
      irreversible inactivators synthesized, Cbz-Phe-Ala-CH=CH-CO-CO-OEt (which
      contains a highly electrophilic alpha-keto ester grouping) was found to be the
      most effective exhibiting, for example, second-order rate constants of
      approximately 1.7 x 10(6)M(-1)min(-1) and approximately 4.9 x 10(4)M(-1)min(-1)
      against recombinant human cathepsin S and human spleenic cathepsin B,
      respectively. This initial study thus holds out the promise that this class of
      inactivator may well be specific for the cysteine protease subclass.

PMID- 17441904
TI  - Characterization and NMR solution structure of a novel cyclic pentapeptide
      inhibitor of pathogenic hantaviruses.
AB  - Hantavirus-induced diseases such as hantavirus cardiopulmonary syndrome and
      hemorrhagic fever with renal syndrome are a global health concern. Hantavirus
      cardiopulmonary syndrome caused by Sin Nombre virus lacks specific therapy and
      its high mortality makes Sin Nombre virus a potential bioweapon agent. Sin Nombre
      virus entry into susceptible cells requires expression of alpha(v)beta(3)
      integrin. We recently reported the sequence of a cyclic nonapeptide that
      inhibited Sin Nombre virus entry into Vero E6 cells at a level comparable to
      ReoPro, a Fab fragment of the anti-beta(3) antibody c7E3. Here, we refine the
      parental peptide, cyclo-[CPFVKTQLC], using alanine scanning and amino acid
      deletions, by optimizing for viral inhibition. The IC(50) of the resulting
      peptide, cyclo-[CPFVC], was 267 microM compared with 263 microM for the parental
      peptide. The solution structure of cyclo-[CPFVC] was determined by two
      dimensional nuclear magnetic resonance spectroscopy, revealing the Phe ring in an
      extended conformation stacked against the Pro ring and containing a beta-turn
      encompassing Val-4 through Cys-1. As an initial step in identifying interactions
      between cyclo-[CPFVC] and its target cellular receptor, the refined peptide
      structure was docked into the ReoPro binding site of integrin beta(3). This
      structure will provide the basis for designing more potent peptidomimetic
      therapeutics to prevent Sin Nombre virus entry and treat hantavirus
      cardiopulmonary syndrome.

PMID- 17441905
TI  - Targeting HIV-1 through molecular modeling and docking studies of CXCR4: leads
      for therapeutic development.
AB  - The chemokine receptor CXCR4 is the receptor for several chemokines and major co
      receptor for X4 human immunodeficiency virus type-1 strains entry into cell. A
      three-dimensional model of human CXCR4 was developed by homology modeling using
      the high-resolution bovine rhodopsin structure as template. Interactions between
      CXCR4 and flavonoids were investigated using in silico docking studies. The
      results underscore the potential of these compounds that they may become
      important new antiviral drugs to combat AIDS. It is worth mentioning also that
      apart from these existing flavonoids, there are many new compounds that may also
      be useful as topical agents to inactivate virus, or may act as adjuvants with
      other antiviral drugs.

PMID- 17441906
TI  - The discovery of novel vascular endothelial growth factor receptor tyrosine
      kinases inhibitors: pharmacophore modeling, virtual screening and docking
      studies.
AB  - We have applied pharmacophore generation, database searching and docking
      methodologies to discover new structures for the design of vascular endothelial
      growth factor receptors, the tyrosine kinase insert domain-containing receptor
      kinase inhibitors. The chemical function based pharmacophore models were built
      for kinase insert domain-containing receptor kinase inhibitors from a set of 10
      known inhibitors using the algorithm HipHop, which is implemented in the CATALYST
      software. The highest scoring HipHop model consists of four features: one
      hydrophobic, one hydrogen bond acceptor, one hydrogen bond donor and one ring
      aromatic function. Using the algorithm CatShape within CATALYST, the bound
      conformation of 4-amino-furo [2, 3-d] pyrimidine binding to kinase insert domain
      containing receptor kinase was used to generate a shape query. A merged shape and
      hypothesis query that is in an appropriate alignment was then built. The combined
      shape and hypothesis model was used as a query to search Maybridge database for
      other potential lead compounds. A total of 39 compounds were retrieved as hits.
      The hits obtained were docked into kinase insert domain-containing receptor
      kinase active site. One novel potential lead was proposed based on CATALYST fit
      value, LigandFit docking scores, and examination of how the hit retain key
      interactions known to be required for kinase binding. This compound inhibited
      vascular endothelial growth factor stimulated kinase insert domain-containing
      receptor phosphorylation in human umbilical vein endothelial cells.

PMID- 17441907
TI  - Multiplex PCR to assay the effect of nucleic acid-based inhibitors on prothrombin
      transcript level.
AB  - We compared an antisense-oligodeoxynucleotide and four DNAzymes directed to the
      prothrombin mRNA for their efficiency to reduce prothrombin transcript level in
      HepG2 cells. The DNAzymes have different binding arm symmetry and cleavage sites,
      but are directed to the identical target site of the antisense
      oligodeoxynucleotide. The nucleic acid-based inhibitors were transfected into
      HepG2 cells and prothrombin transcript level was quantified and normalized to the
      beta-actin transcript level by multiplex PCR. All nucleic acid-based inhibitors
      reduced prothrombin transcript level and the effect was in almost all cases,
      strongest 24 h after transfection, but still remarkable up to 68 h after
      transfection. The antisense-oligodeoxynucleotide was more effective than the
      DNAzymes tested.

PMID- 17441908
TI  - Molecular basis of branched peptides resistance to enzyme proteolysis.
AB  - We found that synthetic peptides in the form of dendrimers become resistant to
      proteolysis. To determine the molecular basis of this resistance, different
      bioactive peptides were synthesized in monomeric, two-branched and tetra-branched
      form and incubated with human plasma and serum. Proteolytic resistance of
      branched multimeric sequences was compared to that of the same peptides
      synthesized as multimeric linear molecules. Unmodified peptides and cleaved
      sequences were detected by high pressure liquid chromatography and mass
      spectrometry. An increase in peptide copies did not increase peptide resistance
      in linear multimeric sequences, whereas multimericity progressively enhanced
      proteolytic stability of branched multimeric peptides. A structure-based
      hypothesis of branched peptide resistance to proteolysis by metallopeptidases is
      presented.

PMID- 17441909
TI  - Fenoprofen and ketoprofen amides as potential antitumor agents.
AB  - Following numerous experimental observations that various non-steroidal anti
      inflammatory drugs have antitumor potentials, a series of fenoprofenamides (1a-g)
      and ketoprofenamides (2a-c) was tested on proliferation of different human tumor
      cell lines and normal human fibroblasts in vitro. Fenoprofen and ketoprofen
      showed modest antiproliferative activity, whereas the growth inhibitory activity
      of the tested amides clearly demonstrates that the substituents linked by an
      amide bond are essential for the significantly stronger cytostatic activity,
      probably because of a greater lipophilicity and/or better cell uptake.
      Additionally, it was shown that the most active derivatives (1d and 2a) induced
      cell cycle arrest at the G1 phase, as well as apoptosis.

PMID- 17441911
TI  - The natural history of untreated renal masses.

PMID- 17441912
TI  - The role of molecular markers in the staging of renal cell carcinoma.

PMID- 17441913
TI  - Prognostic factors in localized renal cell cancer.

PMID- 17441914
TI  - Update on radiological imaging of renal cell carcinoma.
AB  - US is frequently used as the initial imaging in patients with suspected renal
      disease. US contrast agents offer the potential to increase the sensitivity in
      patients who cannot undergo CT or MTI. Harmonic imaging has helped with the
      evaluation of renal cystic lesions. CT remains the reference standard for staging
      and lesion characterization. The rapid technological advances mean that ultra
      thin slices and 3D imaging have now become more widely available. MRI has also
      greatly advanced in speed and image quality, but at present, imaging time and
      scanner availability mean that MRI is generally used as a problem-solving tool.
      It is particularly helpful for smaller lesions and complex cystic lesions, where
      subtraction can be used to accurately identify the presence of enhancement. MRI
      is used as the primary diagnostic tool for patients with radiation concerns and
      those with renal failure. Caution must now also be taken in these patients, given
      the recent studies raising the association of gadolinium-based compounds and NSF.
      There have been dramatic improvements in renal imaging over the last decade,
      offering better resolution, shorter imaging times and better patient acceptance.
      The progress in minimally invasive techniques has driven the need to provide
      better preoperative information to the surgeon. The future of renal imaging is an
      exciting field; perhaps with fluorodeoxyglucose-based positron emission
      tomography we will be able to predict the biological behaviour of a tumour, and
      molecular imaging agents will become available to identify and hopefully treat
      specific tumour types.

PMID- 17441915
TI  - Genetic basis of kidney cancer: a model for developing molecular-targeted
      therapies.

PMID- 17441916
TI  - Renal cell cancer: radical nephrectomy.

PMID- 17441917
TI  - Renal cell carcinoma: vena caval involvement.

PMID- 17441918
TI  - Nephron-sparing surgery.

PMID- 17441919
TI  - Laparoscopic nephrectomy for renal cell cancer: radical and total.

PMID- 17441920
TI  - Laparoscopic partial nephrectomy.

PMID- 17441921
TI  - Renal cryotherapy: a detailed review including a 5-year follow-up.

PMID- 17441922
TI  - Radiofrequency ablation of renal cell carcinoma.

PMID- 17441923
TI  - Ablation of renal tumours with extracorporeal high-intensity focused ultrasound.

PMID- 17441924
TI  - Prognostic factors in renal cell cancer.

PMID- 17441925
TI  - Immunotherapy for metastatic renal cell carcinoma.

PMID- 17441926
TI  - Signal-transduction inhibitors in renal cell carcinoma.

PMID- 17441927
TI  - Anti-angiogenic therapy in renal cell cancer.
AB  - Angiogenesis is an important hallmark of RCC, reflected in the natural history,
      Histology, genetics and now therapeutics of this disease. Clearly, the pro
      angiogenic growth factor VEGF is a functional drug target in RCC and many
      strategies to inhibit this biology have shown clinical benefit. Multi-targeted
      TKI that inhibit VEGFRs have been approved by the FDA as standard treatment for
      advanced RCC. Pharmacodynamyc studies suggest that these agents and others also
      have anti-angiogenic effects. Currently, studies combining VEGFR-targeted
      strategies with other anti-angiogenic agents, including anti-VEGF antibodies, IFN
      or mTOR inhibitors, are underway. However, to what extent the clinical benefit of
      anti-angiogenic strategies in RCC can be built upon is unknown.

PMID- 17441928
TI  - Active and passive immunotherapy: vaccines and antibodies.

PMID- 17441929
TI  - Pain management, supportive and palliative care in patients with renal cell
      carcinoma.

PMID- 17441930
TI  - Laparoscopic partial nephrectomy.

PMID- 17441931
TI  - Repeated cycles of electrical stimulation decrease vasoconstriction and axon
      reflex vasodilation to noradrenaline in the human forearm.
AB  - AIM: To investigate whether desensitization to the vasomotor effects of
      noradrenaline is a specific effect of electrical stimulation. METHODS: Three
      sites on the forearm of 10 healthy volunteers were stimulated with 0.2 mA direct
      current for 2 min twice daily for 10 days. Noradrenaline and histamine were then
      displaced from ring-shaped iontophoresis chambers into two of the pretreated
      sites and two untreated sites on the contralateral forearm. Axon-reflex
      vasodilation was measured from the centre of the ring described by the
      iontophoresis chamber with a laser Doppler flowmeter. One or two days later,
      noradrenaline and vasopressin were introduced into pretreated and untreated sites
      by iontophoresis, and vasoconstriction at sites of administration was measured in
      the heated forearm. RESULTS: The pretreatment blocked vasoconstriction to
      noradrenaline [median increase in flow 1%, interquartile range (IR) -41 to 52%;
      median decrease at the untreated site 53%, IR. -70 to -10%; P < 0.05], but did
      not block vasoconstriction to vasopressin (median decrease 42% at the untreated
      site and 45% at the pretreated site). Axon-reflex vasodilation to noradrenaline
      was diminished at the pretreated site (median increase in flow 33%, IR 2-321%;
      untreated site 247%, IR 31-1087%; P < 0.05). However, axon-reflex vasodilation to
      histamine did not differ significantly between the pretreated site (median
      increase 1085%) and the untreated site (median increase 1345%). CONCLUSIONS: The
      conditioning pretreatment appears to evoke a specific decrease in responsiveness
      to noradrenaline. Repeated cycles of electrical stimulation may downregulate
      neural and vascular responses to noradrenaline by repetitively activating
      cutaneous sympathetic nerve fibres.

PMID- 17441932
TI  - Safety of amlodipine use in patients with acute intermittent porphyria.

PMID- 17441933
TI  - Absence of tolerance and toxicity to high-dose continuous intravenous furosemide
      in haemodynamically unstable infants after cardiac surgery.
AB  - AIM: To evaluate a high-dose continuous furosemide regimen in infants after
      cardiac surgery. METHODS: Fifteen haemodynamically unstable infants with volume
      overload admitted to a paediatric intensive care unit were treated with an
      aggressive furosemide regimen consisting of a loading bolus (1-2 mg kg(-1))
      followed by a continuous infusion at 0.2 mg kg(-1) h(-1) which was adjusted
      according to a target urine output of 4 ml kg(-1) h(-1). Frequent sampling for
      furosemide concentrations in blood and urine was done for 3 days with
      simultaneous assessment of sodium excretion and urine output. RESULTS: The mean
      furosemide dose was 0.22 (+/- 0.06), 0.25 (+/- 0.10) and 0.22 (+/- 0.11) mg kg(
      1) h(-1) on the first, second and third day, respectively. Median urine
      production was 3.0 (0.6-5.3), 4.2 (1.7-6.6) and 3.9 (2.0-8.5) ml kg(-1) h(-1),
      respectively, on the first, second and third day of the study. The target urine
      production was reached at a median time of 24 (6-60) h and this was maintained
      during the study period. The regimen did not result in toxic serum concentrations
      and was haemodynamically well tolerated. CONCLUSION: High-dose continuous
      furosemide infusion for 72 h in haemodynamically unstable infants after cardiac
      surgery appears to be a safe and effective treatment for volume overload.
      Development of tolerance against the effects of furosemide and ototoxic
      furosemide concentrations were not observed.

PMID- 17441934
TI  - Switching statins in Norway after new reimbursement policy: a nationwide
      prescription study.
AB  - AIMS: To assess the changes in prescribing of statins in Norway after
      implementation of the new reimbursement regulations for statins in June 2005.
      METHODS: Data were retrieved from the Norwegian Prescription Database covering
      the total population in Norway (4.6 million). Outcome measures were the
      proportion of atorvastatin users switching to simvastatin and changes in the
      proportion of new statin users receiving simvastatin. Based on retail costs for
      all statin prescriptions dispensed in Norway, expenditure was measured in
      Norwegian currency. RESULTS: One-year prevalences of statin use increased from
      6.3 to 6.8% for women and from 7.5 to 8.1% for men from the year before to the
      year after the new statin regulations. Of atorvastatin users (N = 131,222), 39%
      switched to simvastatin during the 13-month period after the implementation. The
      proportion of switching was higher in women (41%) than in men (36%). In May 2005,
      48% of the new statin users received simvastatin. The proportion of new users
      receiving simvastatin increased rapidly after implementation of the new
      regulations to 68% in June 2005 and reached 92% in June 2006. Expenditure was
      reduced from 120 million to 95 million Euro when comparing the year before with
      the year after the new statin regulations. CONCLUSIONS: The new reimbursement
      policy for statins has had a great impact on physicians' prescribing of statins
      in Norway. Physicians in Norway acknowledge the importance of contributing to
      cost containment.

PMID- 17441952
TI  - Proteomics identifies enhanced expression of stefin A in neonatal murine skin
      compared with adults: functional implications.
AB  - BACKGROUND: Skin develops through a process of epidermal proliferation,
      maturation, and remodelling of the epidermis and dermis. This period also
      involves the maturation of the skin immune system, such that antigen applied
      though the skin of a neonatal mouse always results in immunosuppression, whereas
      in adults, immunity will occur. OBJECTIVES: Using proteomics, to identify
      proteins uniquely involved in the development of the skin and skin immune system.
      METHODS: Proteins were extracted from whole skin of mice aged 4 and 21 days, and
      separated using two-dimensional electrophoresis. RESULTS: Of the 25 proteins that
      were sequenced by peptide mass fingerprinting with matrix-assisted laser
      desorption/ionization-time of flight-mass spectrometry, three were known markers
      of keratinocyte differentiation and proliferation. These were cyclophilin A,
      epidermal fatty acid binding protein 5 and stefin A. Of interest were the two
      isoforms of stefin A, an intracellular protease inhibitor, found in neonatal
      skin. The strong expression of stefin A in neonates was confirmed by
      immunohistochemical analysis, suggesting an important role in the development of
      the epidermis. Additionally, Western blotting identified two larger isoforms in
      adult skin, revealing a change in the stefin A during development. CONCLUSIONS:
      We propose that stefin A is involved in development of the skin, that development
      of the skin and of immune function is linked, and that stefin A has an important
      function in neonatal skin and potentially the neonatal immune response.

PMID- 17441953
TI  - Familial pityriasis rotunda in black-skinned patients; a first report.

PMID- 17441954
TI  - Ciclosporin treatment of psoriasis in a patient with chronic hepatitis C.

PMID- 17441955
TI  - Diffuse cutaneous leishmaniasis responds to miltefosine but then relapses.
AB  - BACKGROUND: Diffuse cutaneous leishmaniasis (DCL), although rare, is profoundly
      incapacitating. At present there is no successful treatment for this progressive
      protozoan infection, which is associated with the absence of specific cell
      mediated immunity (CMI) to Leishmania. This disease shares features with visceral
      leishmaniasis (VL), including specific CMI inactivity during active disease and a
      heavy parasitic burden, but VL responds well to treatment. Miltefosine is the
      first orally administered drug which has shown efficacy in the treatment of VL;
      it has not been adequately evaluated in the treatment of DCL. OBJECTIVES: To
      evaluate the efficacy of miltefosine in the treatment of DCL, using clinical,
      parasitological, histopathological and immunological criteria. METHODS: Sixteen
      patients with DCL were treated with miltefosine, 2.0-2.5 mg kg(-1) daily, for
      variable periods of time (75-218 days). Patients were hospitalized for the first
      month and evaluated every 2 weeks until the termination of treatment with routine
      laboratory chemistry, percentage clinical improvement, presence of parasites in
      skin smears, growth of parasites in culture medium and in hamsters,
      histopathological characteristics of the granulomas, adverse side-effects, and
      reactivity to leishmanin skin test antigen. Further cycles of treatment were
      given in some of these patients, particularly after suspension of treatment was
      followed by relapse. RESULTS: Patients showed dramatic clinical improvement and
      reduction in the parasite burden by day 15 after the initiation of treatment,
      which continued while treatment was maintained. By day 45, 15 patients showed 80
      90% clinical improvement. Nevertheless, suspension of treatment was followed by
      the development of new lesions in all but one patient. Inoculation in hamsters
      was observed to be the most sensitive technique to detect persisting parasites.
      Adverse events were very mild. CONCLUSIONS: Miltefosine produced a dramatic
      clinical and parasitological response in patients with DCL and improvement
      continued during drug administration, but with a single exception all patients
      presented new lesions after suspension of treatment. There was no histological or
      skin test evidence to suggest the development of CMI during treatment, which may
      be an indispensable criterion for the evaluation of potentially effective drugs
      against DCL.

PMID- 17441956
TI  - Multiple dermatomal daughter lesions of postzoster granuloma.

PMID- 17441957
TI  - From the bench to the bedside: proton pump inhibitors can worsen vitiligo.

PMID- 17441958
TI  - Fibroblast growth factor receptor 3 (FGFR3) mutation in a verrucous epidermal
      naevus associated with mild facial dysmorphism.
AB  - We report an activating fibroblast growth factor receptor 3 (FGFR3) mutation
      (R248C) occurring in a verrucous epidermal naevus, and not found in other
      tissues, in a girl with mild facial dysmorphism. We demonstrate the presence of
      the mutation in keratinocytes cultured from the naevus and we speculate that a
      low level of the mutation in other tissues may account for her facial
      dysmorphism. The possibility that the mutation is present in other tissues
      implies a possible risk to her future offspring.

PMID- 17441959
TI  - The prevalence of pili multigemini.

PMID- 17441960
TI  - Interleukin-6 (IL-6) modulates migration and matrix metalloproteinase function in
      dermal fibroblasts from IL-6KO mice.
AB  - BACKGROUND: Interleukin-6-deficient (IL-6KO) mice display significantly delayed
      cutaneous wound healing characterized by decreased re-epithelialization,
      granulation tissue and wound closure. Dermal fibroblasts are one of the principal
      cell types found in granulation tissue and mediate numerous processes during
      healing. OBJECTIVES: To investigate the effects that IL-6 might have on
      granulation tissue formation and fibroblast motility. As fibroblast motility is
      associated with matrix metalloproteinase (MMP) activity, the expression of MMP-2
      and the tissue inhibitors of metalloproteinase (TIMP)-1 and -2 were assessed.
      METHODS: Punch biopsies (4 mm) were performed in the skin of IL-6KO and C57BL/6
      mice. The expression of MMP-2, TIMP-1 and -2 in wound tissue was monitored over
      time. Cellular infiltration and granulation tissue formation was monitored by
      subcutaneous implantation of polyvinyl alcohol (PVA) sponges. A free-floating
      collagen lattice model was also used to investigate the direct effects of IL-6
      treatment on isolated IL-6KO fibroblasts. The expression of MMP-2, and the
      inhibitors TIMP-1 and -2, were assessed via real-time quantitative polymerase
      chain reaction and enzyme-linked immunosorbent assay. RESULTS: IL-6KO wounds
      showed impaired granulation tissue formation 5 days postwounding and fewer
      fibroblasts had populated the PVA matrices 7 days after implantation in IL-6KO
      mice compared with wild-type C57BL/6. The mRNA and protein expression of MMP-2
      and TIMP-2 mRNA was increased in IL-6KO mice compared with wild-type mice beyond
      1 day postwounding, while the expression of TIMP-1 mRNA was transiently higher in
      IL-6KO only 3 days postwounding. Treatment of collagen lattices with various
      concentrations of rmIL-6 again showed a dose-response decrease in mRNA and
      protein expression of MMP-2 and TIMP-2 protein expression, compared with saline
      control, while TIMP-1 did not appear to be significantly modulated. CONCLUSIONS:
      These results indicate that IL-6 influences the function of fibroblasts in
      wounds, and one mechanism of this regulation may be through the modulation of MMP
      2 and TIMP proteins.

PMID- 17441961
TI  - Treatment of localized scleroderma depends on the clinical subtype.

PMID- 17441962
TI  - Involvement of CD147 in regulation of multidrug resistance to P-gp substrate
      drugs and in vitro invasion in breast cancer cells.
AB  - Multidrug resistant (MDR) cancer cells overexpressing P-glycoprotein (P-gp)
      display variations in invasive and metastatic behavior. We aimed to clarify the
      mechanism(s) underlying this observation and transfected vectors carrying CD147,
      a glycoprotein enriched on the surface of tumor cells that stimulates the
      production of matrix metalloproteinases (MMPs), and specific shCD147 into MCF7
      and MCF7/Adr cells, respectively. Using quantitative real-time polymerase chain
      reaction and Western blot, we found that overexpression of CD147 in MCF7 cells up
      regulated MDR1, MMP2, and MMP9 on both transcription and expression levels, which
      promoted tumor cells metastasis and conferred them multidrug resistance to P-gp
      substrate drugs, as determined by in vitro invasion assay and 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. On the other
      hand, silencing of CD147 in MCF7/Adr cells led to the opposite effect. Moreover,
      Erk1/2 in CD147-overexpressing clones were observed to be highly activate and
      after treatment with U0126, an Erk1/2-specific inhibitor, the expression of MDR1,
      MMP2 and MMP9 were decreased significantly. Thus, CD147 may assume a dual role,
      since it had intrinsic stimulative effects on tumor invasion in vitro as well as
      increasing resistance to P-gp substrate drugs.

PMID- 17441963
TI  - Therapeutic potential of the dual-targeted TAS-102 formulation in the treatment
      of gastrointestinal malignancies.
AB  - Current treatment modalities for cancer combine cytotoxic drugs against DNA and
      novel targeted drugs affecting signal transduction pathways, which are required
      for growth progression and metastasizing tumors. Classical chemotherapeutic
      regimens for gastro-intestinal tumors include antimetabolites based on 5
      fluorouracil (5FU), the platinum analog oxaliplatin and the topoisomerase
      inhibitor irinotecan. The thymidine analog trifluorothymidine (TFT) has been
      shown to bypass resistance pathways for 5FU derivatives (S-1, UFT, Xeloda) in
      model systems, while concurrent application with a thymidine phosphorylase
      inhibitor (TPI) increases the bioavailability of TFT, thereby potentiating the in
      vivo efficacy of TFT. The formulation TAS-102 is given orally in a 1.0:0.5 molar
      ratio (TFT:TPI). The formulation is dual-targeted due to the cytotoxic effect of
      TFT, which is enhanced by TPI, while TPI also exerts antiangiogenic effects by
      inhibiting thymidine phosphorylase (TP), also known as platelet-derived
      endothelial cell growth factor. Evidence is accumulating from in vitro and in
      vivo preclinical studies that these properties favor further combinations with
      other cytotoxic agents currently being used in the treatment of gastro-intestinal
      tumors. Also treatment with targeted agents will synergistically down-regulate
      signal transduction pathways responsible for growth and progression of tumors. In
      this review, we summarize the available information on (clinical) pharmacology,
      mechanisms of action, pharmacodynamic and pharmacokinetic properties, early
      clinical trials and future directions of the new potent combination drug TAS-102.

PMID- 17441964
TI  - DNA topoisomerase inhibitor, etoposide, enhances GC-box-dependent promoter
      activity via Sp1 phosphorylation.
AB  - Modification of transcription factors by anticancer agents plays an important
      role in both apoptotic and survival signaling. Here we report that both DNA
      topoisomerase I and II inhibitors such as SN-38 and etoposide, but not cisplatin,
      5-fluorouracil or actinomycin D, can induce phosphorylation of the transcription
      factor Sp1. Furthermore, DNA topoisomerase inhibitors were shown to transactivate
      GC-box-dependent promoters such as the SV40 and vascular endothelial growth
      factor promoters. The phosphorylated form of Sp1 was detectable within 30 min of
      etoposide treatment and was greatly diminished by the presence of the PI3K
      inhibitor wortmannin and by DNA-dependent protein kinase (DNA-PK) knockdown. We
      also confirmed that the phosphorylated form of DNA-PK was increased by treatment
      with both etoposide and SN-38. Taken together, these findings demonstrate a novel
      genomic response to anticancer agents that induce Sp1 phosphorylation, and might
      contribute to tumor progression and drug resistance.

PMID- 17441965
TI  - Treatment of thoracic esophageal carcinoma invading adjacent structures.
AB  - T4 esophageal cancer is defined as the tumor invading adjacent structures, using
      tumor-node-metastasis (TNM) staging. For clinically T4 thoracic esophageal
      carcinoma, multimodality therapy, that is, neoadjuvant chemoradiotherapy (CRT)
      followed by surgery or definitive CRT, has generally been performed. However, the
      prognosis of patients with these tumors remains poor. Another strategy is needed
      to achieve curative treatment. In the present article, the treatment strategies
      employed to date are reviewed. Furthermore, the strategies for these malignancies
      are reassessed, based on our experiences. R1/2 and R0 resections are regarded as
      those with residual and no tumor after surgery. The present data show that
      patients who underwent R1/2 resection after neoadjuvant CRT experienced little
      survival benefit, while complete response (CR) cases after definitive CRT had
      comparatively better results. Therefore, curative surgery should not be attempted
      without down-staging, and definitive CRT should be the initial treatment. Then
      surgery is indicated for the eradication of residual cancer cells. Close
      surveillance is essential for early detection of relapse even after CR, because
      the operation will gradually become increasingly difficult due to post-CRT
      fibrosis. In conclusion, multimodality therapy consists of definitive CRT
      followed by R0 resection, which can be the treatment of choice for T4 esophageal
      carcinoma. These challenging treatments have the potential to constitute the most
      effective therapeutic strategy.

PMID- 17441966
TI  - Carcinogenicity of dimethylarsinic acid in Ogg1-deficient mice.
AB  - Oxidative stress to DNA is recognized as a mechanism underlying carcinogenic
      effects of some environmental agents. Here, we hypothesized that dimethylarsinic
      acid (DMA(V)), an organic metabolite of inorganic arsenic in humans, might exert
      carcinogenic potential in a mouse line carrying a mutant Mmh allele of the
      Mmh/OGG1 gene encoding the enzyme 8-hydroxyguanine DNA glycosylase 1 (OGG1). Ogg1
      mutant and wild type mice were treated with DMA(V) in their drinking water at a
      dose of 200 p.p.m. for up to 72 weeks. All DMA(V)-treated Ogg1(-/-)animals
      developed tumors, with a tendency for lower total incidences in the Ogg1(+/+)
      cases. Lung tumors in particular were induced as compared to the lack in non
      carcinogen controls and were significantly more frequent in the homozygotes. At
      week 4, the levels of DNA 8-OH-dG and cell proliferation were significantly
      elevated in the lungs of non-treated Ogg1(-/-) as compared to Ogg1(+/+) mice and
      were strongly enhanced by DMA(V) treatment. Marked induction of Pola1, Cyp7b1,
      Ndfua3, Mmp13 and other genes specific to cell proliferation, cell signaling and
      xenobiotic metabolism in the lungs of DMA(V)-treated Ogg1(-/-) mice was found.
      Electron microscopic examination revealed the growth of microvilli, with
      increased numbers of mitochondria only in lungs and lung tumors of DMA(V)-exposed
      Ogg1(-/-) mice. Therefore, we strongly suggest that DMA(V) exerts carcinogenicity
      in the lungs of Ogg1(-/-) mutant mice, with a possible role for persistent
      accumulation of DNA oxidative adducts.

PMID- 17441967
TI  - Mixed hyperplastic/adenomatous polyps--a collision.

PMID- 17441968
TI  - Set-up and statistical validation of a new scoring system for obstructed
      defaecation syndrome.
AB  - OBJECTIVE: There is no objective means to assess the obstructed defaecation
      syndrome (ODS), to allow evaluation of outcome or to compare the efficacy of
      treatment including surgery. The study aimed to validate a disease-specific index
      to quantify severity to allow assessment of the results of treatment in clinical
      trials, to permit comparison between them. METHOD: Seventy-six patients with ODS
      and 30 healthy controls entered the study after proctologic and ano-rectal
      physiological investigation. Hirschsprung's disease and slow transit constipation
      were excluded. An eight-item questionnaire with four or five possible answers was
      administered by two independent researchers at two different times. The ODS score
      was the sum of all points with a maximum possible of 31 points. Agreement between
      the two operators was evaluated by the Kappa coefficient for each single item.
      The coefficient of repeatability (CR) was assessed by the Bland and Altman plot.
      The internal consistency was evaluated by the Crohnbach-alpha test. A cluster
      analysis was carried out on each clinical finding. The Mann-Whitney U-test was
      used to compare median ODS score between patients and controls. RESULTS: The ODS
      score of the two operators was normally distributed and strongly correlated (r =
      0.89). The correlation coefficient between the score assigned to each item by two
      operators ranged from 0.79 to 0.98. The degree of agreement between the operators
      was good and the two methods were reproducible (CR = 3.13). There was a
      significant difference between the mean ODS score for patients and controls (t =
      20.70, P < 0.001). The Crohnbach alpha value for internal reliability was +0.513.
      Cluster analysis showed a different profile between cluster 1 (a nonhomogenous
      group including rectocoele, intussusception or perineal descent), and cluster 2
      (pelvic dysynergia). CONCLUSION: The ODS score offers a validated severity of
      disease index in grading the severity of disease and monitoring the efficacy of
      therapy.

PMID- 17441969
TI  - Factors that influence the adequacy of total mesorectal excision for rectal
      cancer.
AB  - OBJECTIVE: In 1997 with the start of CRO7 trial it was agreed that adequacy of
      surgical resection of rectal cancer would be determined by a pathologically
      determined grading of the mesorectum the so called total mesorectal excision
      score (TME score). Scores ranged from 1-3 with 3 being a perfect specimen. The
      aim of this study was to investigate factors which may influence TME scores and
      establish if local recurrence is related to them. METHOD: Data on all patients
      undergoing resectional surgery for rectal cancer in our unit are entered
      prospectively onto a database. Pathology reports of those patients who underwent
      total mesorectal excision were examined and the TME scores added to the database.
      Categorical variables were analysed using the chi2 test, continuous variables
      using ANOVA. Statistical significance was taken as P < 0.05. RESULTS: Between
      January 2000 and June 2005, 518 patients underwent surgery for adenocarcinoma of
      the rectum, of these, 287 patients had a total mesorectal excision for mid or
      lower third tumours under the care of seven colorectal surgeons. All resected
      specimens were scored by a Consultant GI pathologist. Two hundred and fourteen
      patients underwent anterior resection and 73 underwent abdomino-perineal
      resection. The median age of the patients was 73 years (range 38-95 years). One
      hundred and ninety-four patients were male. Seventy-eight patients were treated
      with preoperative radiotherapy, 59 short course and 19 long course. TME scores
      were TME1 n = 30, TME2 n = 99, TME3 n = 158. Fifteen patients developed local
      pelvic recurrence at 2 years. Total mesorectal excision scores were not
      statistically influenced by Dukes' stage, width of tumour, preoperative
      radiotherapy or grade of surgeon. Male patients were statistically more likely to
      have a TME score of 2 or 3 compared with female P = 0.04. Patients undergoing an
      anterior resection were statistically more likely to have a TME score of 2 or 3
      compared with abdomino-perineal resection P = 0.0001. Tumours with a
      circumferential resection margin (CRM) of more than 1 mm were more likely to have
      a TME score of 2 or 3 score (P = 0.0001). There was no relationship between TME
      and local recurrence (P = 0.966). CONCLUSION: There is no relationship between
      the TME score in patients undergoing resectional surgery for adenocarcinoma of
      the rectum and the development of local recurrence at 2 years. Other factors such
      as CRM involvement are more likely to have an impact on local recurrence. The
      factors that influence the quality of TME are the operative procedure of anterior
      resection, male gender and CRM positivity. There appear to be no deleterious
      effects on the TME score by Specialist Registrars performing the operation under
      Consultant supervision. While TME scores may be an index of a technical
      performance, they appear to have little role in predicting future outcomes.

PMID- 17441970
TI  - Partial atrophic tongue other than median rhomboid glossitis.
AB  - A group of 23 patients with partial atrophic change of the tongue was examined
      for candidiasis. All of them reported pain in the tongue on eating hot or spicy
      food. The intensity of the tongue pain was evaluated before and after treatment
      using a visual analogue scale. Of the 23 patients, 10 (43.5%) had predisposing
      factors for candidiasis such as diabetes mellitus and anaemia. In the culture
      examination, candidal species were isolated in 65.2%, all Candida albicans.
      Direct cytological examination performed in 10 of the 23 patients revealed fungal
      pseudohyphae in 8 patients. After antifungal treatment, tongue pain had
      disappeared or improved markedly in 82.6%. Simultaneously, the filiform papilla
      of the atrophic site was observed to have begun to regenerate in these patients.
      Candida infection should be suspected in patients with partial atrophic tongue
      associated with pain on eating.

PMID- 17441971
TI  - Topiramate reduces headache days in chronic migraine: a randomized, double-blind,
      placebo-controlled study.
AB  - The aim of this study was to evaluate the efficacy and tolerability of topiramate
      for the prevention of chronic migraine in a randomized, double-blind, placebo
      controlled trial. Chronic migraine is a common form of disabling headache
      presenting in headache subspecialty practice. Preventive treatments are essential
      for chronic migraine management, although there are few or no controlled
      empirical trial data on their use in this patient population. Topiramate is
      approved for the prophylaxis of migraine headache in adults. Patients (18-65
      years) who experienced chronic migraine (defined as > or =15 monthly migraine
      days) for > or =3 months prior to trial entry and had > or =12 migraine days
      during the 4-week (28-day) baseline phase were randomized to topiramate or
      placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly)
      to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200
      mg/day, according to patient need. Existing migraine preventive treatments,
      except for antiepileptic drugs, were continued throughout the trial. The primary
      efficacy measure was the change in number of migraine days from the 28-day
      baseline phase to the last 28 days of the double-blind phase in the intent-to
      treat population, which consisted of all patients who received at least one dose
      of study medication and had one outcome assessment during the double-blind phase.
      Health-related quality of life was evaluated with the Migraine Specific Quality
      of Life Questionnaire (MSQ, Version 2.1), the Headache Impact Test (HIT-6) and
      the Migraine Disability Assessment (MIDAS) questionnaires, and tolerability was
      assessed by adverse event (AE) reports and early trial discontinuations. Eighty
      two patients were screened. Thirty-two patients in the intent-to-treat population
      (mean age 46 years; 75% female) received topiramate (mean modal dose +/- SD = 100
      +/- 17 mg/day) and 27 patients received placebo. Mean (+/-SD) baseline number of
      migraine days per 4 weeks was 15.5 +/- 4.6 in the topiramate group and 16.4 +/-
      4.4 in the placebo group. Most patients (78%) met the definition for acute
      medication overuse at baseline. The mean duration of treatment was 100 and 92
      days for topiramate- and placebo-treated patients, respectively. Study completion
      rates for topiramate- and placebo-treated patients were 75% and 52%,
      respectively. Topiramate significantly reduced the mean number of monthly
      migraine days (+/-SD) by 3.5 +/- 6.3, compared with placebo (-0.2 +/- 4.7, P <
      0.05). No significant intergroup differences were found for MSQ and HIT-6. MIDAS
      showed improvement with the topiramate treatment group (P = 0.042 vs. placebo).
      Treatment emergent adverse events were reported by 75% of topiramate-treated
      patients (37%, placebo). The most common AEs, paraesthesia, nausea, dizziness,
      dyspepsia, fatigue, anorexia and disturbance in attention, were reported by 53%,
      9%, 6%, 6%, 6%, 6% and 6% of topiramate-treated patients, respectively, vs. 7%,
      0%, 0%, 0%, 0%, 4% and 4% of placebo-treated patients. This randomized, double
      blind, placebo-controlled trial demonstrates that topiramate is effective and
      reasonably well tolerated when used for the preventive treatment of chronic
      migraine, even in the presence of medication overuse.

PMID- 17441972
TI  - Headache and temporomandibular disorders: evidence for diagnostic and behavioural
      overlap.
AB  - To assess the diagnostic and behavioural overlap of headache patients with
      temporomandibular disorders (TMD), individuals recruited from the general
      population with self-described headaches were compared with non-headache
      controls. The examination and diagnostic procedures in the Research Diagnostic
      Criteria (RDC) for TMD were applied to both sets of subjects by a blinded
      examiner. Following their examination, subjects used experience sampling methods
      to obtain data on pain, tooth contact, masticatory muscle tension, emotional
      states and stress. Results showed that a significantly higher proportion of the
      headache patients received an RDC/TMD diagnosis of myofascial pain than non
      headache controls. Headache patients also reported significantly more frequent
      and intense tooth contact, more masticatory muscle tension, more stress and more
      pain in the face/head and other parts of the body than non-headache controls.
      These results are similar to those reported for TMD patients and they suggest
      that headache patients and TMD patients overlap considerably in diagnosis and
      oral parafunctional behaviours.

PMID- 17441973
TI  - Interaction of calcitonin gene-related peptide, nitric oxide and histamine
      release in neurogenic blood flow and afferent activation in the rat cranial dura
      mater.
AB  - Calcitonin gene-related peptide (CGRP), nitric oxide (NO) and histamine are
      implicated in primary headaches but their role in vascular and nociceptive events
      in the dura mater is not well described. In an in vitro preparation of the
      hemisected rat skull, CGRP and histamine release from the cranial dura was
      measured using enzyme-linked immunoassays. While the NO donator NONO(ate) (10(-4)
      M) was without effect, CGRP (10(-5) M) induced considerable histamine release
      from the rat cranial dura, which was blocked by the CGRP receptor antagonist
      CGRP(8-37) (10(-5) M). Conversely, histamine (10(-4) M) did not stimulate CGRP
      release. In vitro recordings from single rat meningeal afferents showed that only
      one of 12 mechanically identified units but several mechanically insensitive
      units responded to histamine (up to 10(-5) M). Increases in meningeal blood flow
      after histamine application (10(-4) M) to the rat cranial dura remained unchanged
      during CGRP receptor blockade with CGRP(8-37), inhibition of NO synthesis with L
      NAME (20 mg/kg i.v.) and H(3) receptor blockade with thioperamide (10(-4) M). We
      conclude that histamine produces direct vasodilatation and activates a subset of
      largely non-mechanically sensitive, non-CGRP containing afferents in the rat
      meninges. Histamine is released from meningeal mast cells which are stimulated by
      CGRP. Similar mechanisms may be involved in the pathogenesis of headaches.

PMID- 17441974
TI  - Evolution, antimicrobial susceptibility and assignment to international clones of
      methicillin-resistant Staphylococcus aureus isolated over a 9-year period in two
      Spanish hospitals.
AB  - Antimicrobial resistance profiles, restriction fragment length polymorphism of
      the coagulase gene and repetitive element sequence-based PCR were used to
      classify 210 methicillin-resistant Staphylococcus aureus isolates recovered
      between 1997 and 2005 in two hospitals in Vigo, north-west Spain. Representative
      isolates belonging to the epidemic clones were analysed by spa typing and
      multilocus sequence typing, and the staphylococcal chromosomal cassette (SCC)mec
      type was determined for all isolates. The New York/Japan clone (t002-ST5-II) was
      detected in Spain for the first time. However, the New York/Japan and the
      Brazilian (t037-ST239-IIIA) clones were replaced by EMRSA-16 (t018-ST36-II),
      which at present is the predominant clone.

PMID- 17441975
TI  - Quality assessment of conjunctival specimens for detection of Chlamydia
      trachomatis by PCR in children with active trachoma.
AB  - One component of control programmes to eliminate trachoma is the treatment of
      Chlamydia trachomatis infection. A diagnosis of trachoma is based on clinical
      grounds, but the signs of active trachoma do not always correlate with the
      presence of C. trachomatis. During a therapeutic trial, the level of C.
      trachomatis infection in children with active trachoma in Guinea and Pakistan was
      assessed using a qualitative commercially available PCR that targeted the C.
      trachomatis plasmid. The influence of the quality of specimens on the efficiency
      of the PCR was investigated using two quantitative real-time PCRs targeting the
      specific omp1 gene of C. trachomatis and human chromosomal DNA, respectively. C.
      trachomatis was detected in c. 23% of children (aged 1-10 years) who presented
      with clinically active trachoma. Controls showed that PCR-related problems did
      not influence this detection rate. For 14% of the positive samples, C.
      trachomatis was detected in only one eye, with a significantly lower mean load of
      bacteria. These results suggest that epidemiological and therapeutic surveys
      should be conducted by sampling and testing both eyes. Moreover, the high
      variability of the cell load observed in the conjunctival swabs suggests that the
      effectiveness of swabbing may be questionable.

PMID- 17441976
TI  - Estimation of delay in detecting hepatitis C virus antibodies in pools compared
      to individual testing on seroconversion panels.
AB  - Testing for anti-hepatitis C virus (HCV) antibodies in pools may reduce blood
      screening costs, making this approach affordable for developing countries,
      provided that the dilution of infected blood does not significantly increase the
      number of undetectable viral particles, especially in seroconverters. This study
      assessed the delay in detection of HCV antibodies in five HCV seroconversion
      panels, tested in pools of 6-48 samples, and estimated the risk of transfusion
      transmitted HCV caused by pooling. The delay in detection of positive samples was
      5-12 days for pools of all sizes, adding 7% to the risk of HCV transmission that
      occurs when blood donors' samples are tested individually.

PMID- 17441977
TI  - Evaluation of a new point-of-care test for influenza A and B virus in travellers
      with influenza-like symptoms.
AB  - Point-of-care (POC) tests for influenza facilitate clinical case management, and
      might also be helpful in the care of travellers who are at special risk for
      influenza infection. To evaluate influenza POC testing in travellers, a new
      assay, the ImmunoCard STAT! Flu A and B, was used to investigate travellers
      presenting with influenza-like symptoms. Influenza virus infection was diagnosed
      in 27 (13%) of 203 patients by influenza virus-specific PCR and viral culture.
      The POC test had sensitivity and specificity values of 64% and 99% for influenza
      A, and 67% and 100% for influenza B, respectively. Combined sensitivity and
      specificity were 67% and 99%, respectively, yielding positive and negative
      predictive values of 95%, and positive and negative likelihood ratios of 117 and
      0.34, respectively. The convenient application, excellent specificity and high
      positive likelihood ratio of the POC test allowed rapid identification of
      influenza cases. However, negative test results might require confirmation by
      other methods because of limitations in sensitivity. Overall, influenza POC
      testing appeared to be a useful tool for the management of travellers with
      influenza-like symptoms.

PMID- 17441978
TI  - Antibiotic treatment for patients with acute exacerbations of chronic bronchitis.

PMID- 17441979
TI  - Cerebrospinal fluid cytokines in enterovirus 71 brain stem encephalitis and
      echovirus meningitis infections of varying severity.
AB  - Taiwan has experienced several outbreaks of enterovirus 71 (EV71) infections
      since 1998. This study examined the quantitative relationship between specific
      cytokines in the cerebrospinal fluid (CSF) and the severity of EV71 brain stem
      encephalitis (BE), and investigated whether the CSF cytokine response differed
      from that to uncomplicated echovirus meningitis (EM). The study included 57
      children with EV71 BE, of whom 24 had isolated BE, 24 had autonomic nervous
      system (ANS) dysregulation, and nine had pulmonary oedema (PE), and 15 children
      with EM. All were confirmed by virus culture. Mean CSF glucose, total protein and
      lactate levels were increased significantly in association with the severity of
      EV71 BE. The mean CSF concentration of interleukin (IL)-1beta in children with
      EV71 PE was significantly higher than in those with isolated BE. IL-6 and
      interferon (IFN)-gamma levels were significantly higher for EV71 PE and ANS
      dysregulation than for isolated BE. In contrast, EM was associated with high
      levels of IL-1beta and low levels of IFN-gamma. Cytokines in the central nervous
      system, as well as in blood, appear to be involved in the pathogenesis of EV71
      BE.

PMID- 17441980
TI  - Computer-guided flapless placement and immediate loading of four conical screw
      type implants in the edentulous mandible.
AB  - AIM: The aim of this prospective study was to evaluate the outcome of computer
      guided flapless placement and immediate loading of four conical screw-type
      implants in the interforaminal region. PATIENTS AND METHODS: From May to August
      2003, 25 consecutive patients (m : f=16 : 9) with edentulous mandibles were
      included in the study. After transmucosal drilling with computer-assisted
      navigation, four implants were placed in the interforaminal region. The lower
      dentures were converted and implants immediately loaded. RESULTS: One-hundred
      implants were successfully placed. In two patients, all implants had to be
      submerged because of insufficient primary stability of one of the implants;
      another patient declined to receive immediate loading of implants after surgery
      and was lost to follow-up. During follow-up of the remaining 22 patients with 88
      immediately loaded implants, loosening of four implants (4.5%) was seen in three
      patients. In these cases, immediate loading was terminated and all implants
      submerged; subsequently, two implants were lost in one patient, while the other
      two implants re-osseointegrated. The cumulative survival and success rates of
      immediately loaded implants were 97.7% after 2 years. Prosthetic success was
      100%. CONCLUSION: Transmucosal computer-assisted placement and immediate loading
      of mandibular implants is a high-end approach to edentulism that provides
      excellent results while being minimally invasive.

PMID- 17441981
TI  - A novel bone scraper for intraoral harvesting: a device for filling small bone
      defects.
AB  - AIM: To evaluate histologically the morphology and characteristics of bone chips
      harvested intraorally by Safescraper, a specially designed cortical bone
      collector. MATERIAL AND METHODS: Bone chips harvested near a bone defect or in
      other intraoral sites were grafted into a post-extractive socket or applied in
      procedures for maxillary sinus floor augmentation or guided bone regeneration.
      Core biopsies were performed at implant insertion. Undecalcified specimens
      embedded in PMMA were studied by histology, histochemistry and SEM. RESULTS:
      Intraoral harvesting by Safescraper provided a simple, clinically effective
      regenerative procedure with low morbidity for collecting cortical bone chips (0.9
      1.7 mm in length, roughly 100 microm thick). Chips had an oblong or quadrangular
      shape and contained live osteocytes (mean viability: 45-72%). Bone chip grafting
      produced newly formed bone tissue suitable for implant insertion. Trabecular bone
      volume measured on biopsies decreased with time (from 45-55% to 23%). Grafted
      chips made up 50% or less of the calcified tissue in biopsies. Biopsies presented
      remodeling activities, new bone formation by apposition and live osteocytes (35%
      or higher). DISCUSSION AND CONCLUSIONS: In conclusion, Safescraper is capable of
      collecting adequate amounts of cortical bone chips from different intraoral
      sites. The procedure is effective for treating alveolar defects for endosseous
      implant insertion and provides good healing of small bone defects after grafting
      with bone chips. The study indicates that Safescraper is a very useful device for
      in-office bone harvesting procedures in routine peri-implant bone regeneration.

PMID- 17441982
TI  - Treatment of a commercial, machined surface titanium implant with H2SO4/H2O2
      enhances contact osteogenesis.
AB  - BACKGROUND: It has recently been reported that controlled chemical oxidation of
      titanium (Ti) with sulfuric acid (H(2)SO(4))/hydrogen peroxide (H(2)O(2))
      significantly influences the early stages of in vitro osteogenesis. The aim of
      this study was to evaluate whether this chemical treatment can also influence in
      vivo bone formation. MATERIAL AND METHODS: Ti implants (Mk III) were etched with
      H(2)SO(4)/H(2)O(2) for 4 h at room temperature. Mandibular premolars were
      extracted in eight dogs and, after 3 months, three treated and three untreated
      implants were placed in each animal. At 3 and 8 weeks postimplantation, the
      animals were sacrificed, and the implants with surrounding bone were harvested,
      fixed with formaldehyde, and processed for embedding in LR White. Sections of
      bone with the implants were prepared, stained with Stevenel's blue and Alizarin
      red, and analyzed histomorphometrically for percentage of bone-to-implant contact
      (BIC), percentage of mineralized bone area between threads (BABT), and percentage
      of mineralized bone area within the mirror area (BAMA). Data were analyzed
      statistically using two-way analysis of variance. RESULTS: Treated implants
      exhibited significantly more (P<0.05) BIC than control, untreated ones both at 3
      (68.1% vs. 27.9%) and 8 weeks (73.5% vs. 14.7%) postimplantation. However, there
      was no difference in the BABT and BAMA. Histological analysis confirmed that, in
      most cases, new bone in contact with the implant formed in a direction away from
      it. CONCLUSIONS: These data indicate that a controlled chemical oxidation of Ti
      implants significantly enhances contact osteogenesis and suggest that this
      treatment may be beneficial for early loading of implants.

PMID- 17441983
TI  - Effect of microthread on the maintenance of marginal bone level: a 3-year
      prospective study.
AB  - OBJECTIVES: The purpose of the present study was to evaluate the long-term effect
      of the microthread on the maintenance of marginal bone level. MATERIAL AND
      METHODS: Seventeen patients were selected and two types of Astra Tech implants
      were installed, with the Microthread on the coronal portion of the fixture [Astra
      Tech Single Tooth Implant (ST)] or without the Microthread [Astra Tech TiOblast
      Implant (TB)]. ST and TB were installed adjacent to each other within the same
      partially edentulous sites and marginal bone loss was evaluated by radiographic
      image. The marginal bone-level alteration of the each fixture after prosthesis
      insertion was analyzed. RESULTS: The marginal bone loss of ST and TB differed
      significantly during the observation period (P<0.01). Marginal bone levels of
      both ST and TB were stabilized after 1 year of lading. CONCLUSIONS: The
      Microthread might have an effect in maintaining the marginal bone loss against
      loading.

PMID- 17441984
TI  - Rab11B small GTPase regulates secretion of cysteine proteases in the enteric
      protozoan parasite Entamoeba histolytica.
AB  - Vesicular trafficking plays a pivotal role in the virulence of the enteric
      protozoan parasite Entamoeba histolytica. In the present study, we showed that
      one isotype of the small GTPase Rab11, EhRab11B, plays a central role in the
      secretion of a major virulence factor, cysteine proteases. EhRab11B did not
      colocalize with markers for the endoplasmic reticulum, early endosomes and
      lysosomes, but was partially associated with non-acidified vesicles in the
      endocytic pathway, likely recycling endosomes. Overexpression of EhRab11B
      resulted in a remarkable increase in both intracellular and secreted cysteine
      protease activity, concomitant with an augmentation of cytolytic activity as
      demonstrated by an increased ability to destroy mammalian cells. The
      oversecretion of cysteine proteases with EhRab11B overexpression was neither
      sensitive to brefeldin A nor specific to a certain cysteine protease species
      (e.g. CP1, 2 or 5), suggesting that these three major cysteine proteases are
      trafficked via an EhRab11B-associated secretory pathway, which is distinct from
      the classical brefeldin-sensitive pathway. Overexpression of EhRab11B also
      enhanced exocytosis of the incorporated fluid-phase marker, supporting the notion
      that it is involved in recycling. This is the first report demonstrating that
      Rab11 plays a central role in the transport and secretion of pathogenic factors.

PMID- 17441985
TI  - Cell wall-associated alpha-glucan is instrumental for Mycobacterium tuberculosis
      to block CD1 molecule expression and disable the function of dendritic cell
      derived from infected monocyte.
AB  - We previously described an escape mechanism exploited by Mycobacterium
      tuberculosis (Mtb) to prevent the generation of fully competent dendritic cells
      (DC). We have now tested the effect of isolated mycobacterial components on human
      monocyte differentiation into DC and demonstrated that cell wall (CW)-associated
      alpha-glucan induces monocytes to differentiate into DC (Glu-MoDC) with the same
      altered phenotype and functional behaviour of DC derived from Mtb-infected
      monocytes (Mt-MoDC). In fact, Glu-MoDC lack CD1 molecule expression, fail to
      upregulate CD80 and produce IL-10 but not IL-12. We also showed that Glu-MoDC are
      not able to prime effector T cells or present lipid antigens to CD1-restricted T
      cell clones. Thus, we propose a mechanism of Mtb-monocyte interaction mediated by
      CW-associated alpha-glucan, which allows the bacterium to evade both innate and
      acquired immune responses.

PMID- 17441986
TI  - Bacterial cytolethal distending toxin promotes the development of dysplasia in a
      model of microbially induced hepatocarcinogenesis.
AB  - Bacterial cytolethal distending toxins (CDTs) containing DNase I-like activity
      can induce limited host DNA damage that leads to activation of the DNA-damage
      repair responses in cultured cell lines. However, in vivo experimental evidence
      linking CDTs to carcinogenesis is lacking. In this study, infection of A/JCr mice
      with an isogenic mutant of Helicobacter hepaticus lacking CDT activity (CDT
      mutant) induced chronic hepatitis comparable to wild-type H. hepaticus (Hh)
      infection at both 4 and 10 months post inoculation (MPI); however, the CDT mutant
      infected mice did not develop hepatic dysplasic nodules at 10 MPI, whereas those
      infected with Hh did. There was no significant difference in hepatic colonization
      levels between the CDT mutant and Hh at both time points (P > 0.05). At 4 MPI,
      mice infected with Hh had significantly enhanced hepatic transcription of
      proinflammatory TNF-alpha, IFN-gamma and Cox-2, growth mediators IL-6 and TGF
      alpha, anti-apoptotic Bcl-2 and Bcl-X(L), and increased hepatocyte proliferation
      (P < 0.05) compared with the control or the CDT mutant-infected mice. In
      addition, Hh infected male mice had upregulated hepatic mRNA levels of RelA
      (p65), p50, GADD45beta and c-IAP1, components of the NF-kappaB pathway compared
      with the CDT mutant-infected mice. At 10 MPI, Hh infection was associated with
      significant upregulation of IL-6 mRNA. Activation of the inflammatory NF-kappaB
      pathway and upregulation of proinflammatory cytokines plus IL-6 in the Hh but not
      in the CDT mutant-infected mice suggest that Hh CDT plays a key role in promoting
      the dysplastic changes in Hh-infected mouse livers.

PMID- 17441987
TI  - Brucella requires a functional Type IV secretion system to elicit innate immune
      responses in mice.
AB  - The virB operon, encoding a Type IV secretion system (T4SS), is essential for
      intracellular survival and persistent infection by Brucella spp. To better
      understand the role of the T4SS in evading host defence mechanisms and
      establishing chronic infection, we compared transcriptional profiles of the host
      response to infection with wild-type and virB mutant Brucella strains. Analysis
      of gene expression profiles in murine splenocytes 3 days after inoculation with
      wild-type Brucella strains revealed an inflammatory response, with a prominent
      upregulation of genes induced by both type I and type II interferons. Real-time
      RT-PCR showed that a group of genes from these pathways were induced by day 3
      post infection and declined to baseline levels by day 7. In contrast, neither of
      the two virB mutant strains elicited a proinflammatory gene expression profile,
      demonstrating that the T4SS was required to trigger this response. Infection
      studies using type I interferon receptor knockout mice showed that a lack of type
      I interferon signalling did not affect Brucella replication during the first 4
      weeks of infection. Thus, induction of type I interferons does not appear to be
      an essential mechanism by which the T4SS promotes persistent infection by
      Brucella.

PMID- 17441988
TI  - The incidence of first provoked and unprovoked seizure in pediatric patients with
      and without psychiatric diagnoses.
AB  - PURPOSE: To estimate the rate of new-onset afebrile provoked and unprovoked
      seizure in a general pediatric population and subgroups of patients with and
      without psychiatric diagnoses other than attention deficit hyperactivity disorder
      (ADHD). METHODS: A retrospective cohort study of 133,440 pediatric patients,
      between the ages of 6 and 17 years, and without history of seizure or prior use
      of anticonvulsant medications, with follow-up during 2003. The data source for
      this study was Ingenix's research database containing pharmacy and medical claims
      for members of a large US-based managed care organization. The main outcome
      measure was new-onset nonfebrile seizure. Incidence rates of seizure and 95%
      confidence intervals (CI) were calculated and expressed as rates per 100,000
      person-years. RESULTS: There were 132 new-onset provoked and unprovoked seizures
      in 78,423 person-years of follow-up among the general pediatric population
      sample. The incidence rate of seizure among the general pediatric population was
      168 per 100,000 p-y (95% CI 141-200). The incidence rate of seizure among
      patients without psychiatric diagnoses was 149 per 100,000 p-y (95% CI 122-180).
      The incidence rate of seizure among patients with psychiatric diagnoses other
      than ADHD was 513 per 100,000 p-y (95% CI 273-878). There were increases in the
      incidence rates of seizure in all of the seizure risk factor groups, but this was
      more pronounced among males ages 6-12 with psychiatric diagnoses. CONCLUSIONS:
      The results of this study are consistent with previous reports showing that
      pediatric patients with psychiatric disorders have a higher incidence rate of
      seizure than the general pediatric population.

PMID- 17441989
TI  - Pathological tau tangles localize to focal cortical dysplasia in older patients.
AB  - PURPOSE: Reactivation of neurodevelopmental processes may contribute to
      neurodegeneration. For example, the proteins cyclin dependent kinase 5 (cdk5) and
      glycogen synthase kinase 3 beta (GSK3beta), which are essential to normal
      cortical development, can hyperphosphorylate tau and might contribute to the
      pathogenesis of Alzheimer's disease. Focal cortical dysplasia (FCD) is an
      important neurodevelopmental cause of refractory human epilepsy within which
      dysplastic neurons exhibit increased immunoreactivity for cdk5 and GSK3beta as
      well as neurofilamentous accumulations. We therefore hypothesized that the
      developmentally abnormal cortex of FCD might be more susceptible to tau-mediated
      neurodegeneration than adjacent histologically normal cortex. MATERIALS AND
      METHODS: We examined a series of 15 cases of FCD, spanning a wide age range, for
      beta-amyloid, pathologically phosphorylated tau and neurofibrillary tangles using
      silver staining, immunohistochemistry for tau, AT8, RD3, RD4 and two-dimensional
      cell counting. RESULTS: Beta-amyloid plaques, aberrantly phosphorylated tau and
      neurofibrillary tangles are only found in older patients. The hyperphosphorylated
      tau tangles are confined to dysplastic neurons. Immunoreactivity for 3- and 4
      repeat tau was again only detected within regions of FCD in older patients. With
      increasing age, the dysplastic cortex became hypocellular and a higher proportion
      of dysplastic neurons exhibited pathological tau phosphorylation. CONCLUSIONS: In
      older patients, FCD appears more susceptible to formation of pathologically
      phosphorylated tau neurofibrillary tangles than adjacent histologically normal
      cortex. Our results suggest a novel convergence of pathological neurodevelopment
      with pathological age-related neurodegeneration.

PMID- 17441990
TI  - An epidemiological study of children with status epilepticus in Okayama, Japan.
AB  - BACKGROUND: The incidence of status epilepticus (SE) in Asian children, including
      Japanese, has not been reported. METHODS: In 2003, we performed an
      epidemiological study of SE on Japanese children (31 days or older to <15 years
      of age) in Okayama City by ascertaining all lifetime first episodes of SE.
      RESULTS: Thirty-seven patients (22 males and 15 females) were identified. The
      annual incidence of SE was 38.8 per 100,000 population (95% CI: 24.5-49.5).
      Febrile SE in the absence of CNS infection accounted for 17. Acute symptomatic
      etiologies other than febrile SE were observed in eight patients, including three
      cases of influenza encephalitis/encephalopathy. Five were classified as remote
      symptomatic and the remaining seven as cryptogenic. The highest incidence
      (155.1/100,000) was seen in the age range of 31 days or older to <1 year,
      followed by 101.5/100,000 in the age range of one year, and the incidence
      decreased after eight years. In 26 of the 37 patients, SE was their first
      seizure. As for seizure types, 32 had convulsive SE, including tonic status in
      one. Five others showed nonconvulsive SE, including complex partial SE in four
      and absence status in one. No one died of SE. Two patients who brought on SE
      because of influenza encephalitis/encephalopathy suffered from motor disturbance
      with or without mental disturbance after SE. CONCLUSIONS: The incidence of SE
      tended to be higher in Japanese children than reported in Caucasians. The
      Japanese had an age-specific incidence pattern similar to that of Caucasians.

PMID- 17441991
TI  - Evaluation of subcortical white matter and deep white matter tracts in
      malformations of cortical development.
AB  - AIMS: Abnormal cortical development will lead to abnormal axons in white matter.
      The purpose was to investigate (1) the microstructural changes in subcortical
      white matter adjacent to malformations of cortical development (MCD) and (2) the
      deep white matter tracts using diffusion tensor imaging (DTI). METHODS: Thirteen
      children with a variety of MCD were recruited. The fractional anisotropy (FA),
      trace, and eigenvalues (lambdamajor, lambdamedium, lambdaminor) of subcortical
      white matter of MCD were compared with contralateral normal side. The deep white
      matter tracts were graded based on the size, color hues and displacement of the
      tracts as visualized on color vector maps and tractography; grade 1 was normal
      tract size and color hue, grade 2 was reduced tract size but preserved color hue
      and grade 3 was loss of color hue or failure of tracking on tractography.
      RESULTS: The subcortical white matter adjacent to abnormal cortex demonstrated
      reduced FA (p < 0.05) and tendency to increase trace (p = 0.06). There was a
      significant elevation in lambdamedium and lambdaminor (p < 0.05), but no
      significant change in lambdamajor (p > 0.05). Twelve cases demonstrated
      alteration in white matter tracts. Seven cases of focal cortical dysplasia and
      two cases of transmantle MCD demonstrated grade 3 pattern of white matter tract.
      CONCLUSION: Reduced FA is a sensitive but nonspecific marker of alteration in
      microstructure of white matter. The elevated lambdamedium and lambdaminor may
      reflect a dominant effect of abnormal myelin. Alteration in white matter tracts
      was observed in most cases of MCD.

PMID- 17441992
TI  - Diminished response of CA1 neurons to antiepileptic drugs in chronic epilepsy.
AB  - PURPOSE: A substantial proportion of epilepsy patients ( approximately 30%)
      continue to have seizures despite carefully optimized treatment with
      antiepileptic drugs (AEDs). One key concept to explain the development of
      pharmacoresistance is that epilepsy-related changes in the properties of CNS drug
      targets result in AED-insensitivity of these targets. These changes then
      contribute to drug-resistance on a clinical level. We have tested this hypothesis
      in hippocampal CA1 neurons in experimental epilepsy. METHODS: Using patch-clamp
      techniques, we thoroughly examined the effects of carbamazepine (CBZ) and
      phenytoin (PHT) on voltage-gated Na(+) currents (I(Na)) in hippocampal CA1
      neurons of sham-control and chronically epileptic rats. RESULTS: We find that
      there were significant changes in the effects of PHT, but not CBZ on the voltage
      dependence of inactivation, resulting in a significant reduction in voltage
      dependent blocking effects in chronically epileptic animals. Conversely, CBZ
      effects on the time course of recovery from inactivation of I(Na) were
      significantly less pronounced in epileptic compared to sham-control animals,
      whereas PHT effects remained unaltered. CONCLUSIONS: Our findings indicate that
      AED-sensitivity of Na(+) currents is reduced in chronic epilepsy. The reduction
      in sensitivity is due to different biophysical mechanisms for CBZ and PHT.
      Furthermore, comparison to published work suggests that the loss of AED
      sensitivity is less pronounced in CA1 neurons than in dentate granule neurons.
      Thus, these results suggest that target mechanisms of drug resistance are cell
      type and AED specific. Unraveling these complex mechanisms is likely to be
      important for a better understanding of the cellular basis of drug-resistant
      epilepsy.

PMID- 17441993
TI  - Status epilepticus triggers caspase-3 activation and necrosis in the immature rat
      brain.
AB  - The mode and mechanism of neuronal death induced by status epilepticus (SE) in
      the immature brain have not been fully characterized. In this study, we analyzed
      the contribution of neuronal necrosis and caspase-3 activation to CA1 damage
      following lithium-pilocarpine SE in P14 rat pups. By electron microscopy, many
      CA1 neurons displayed evidence of early necrosis 6 hours following SE, and the
      full ultrastructural features of necrosis at 24-72 hours. Caspase-3 was activated
      in injured (acidophilic) neurons 24 hours following SE, raising the possibility
      that they died by caspase-dependent "programmed" necrosis.

PMID- 17441994
TI  - Sodium valproate, hyperandrogenism and altered ovarian function in Indian women
      with epilepsy: a prospective study.
AB  - PURPOSE: To assess the association of long-term sodium valproate therapy with
      reproductive endocrine disorders in Indian women with generalized epilepsy.
      METHODS: Clinical parameters, ovarian morphology, and serum reproductive hormone
      concentrations were evaluated in 30 clinically normal and eumenorrheic
      reproductive age women with generalized epilepsy who were newly initiated on
      valproate. Longitudinal evaluations were done in 25 of these women after 1 year,
      and in some of them after 2 and 3 years of therapy. RESULTS: Of the 25 women who
      completed 1 year follow-up, we observed clinically relevant weight gain in 40%,
      hirsutism in 20%, menstrual abnormalities in 24%, polycystic ovaries (PCO) in
      16%, polycystic ovarian syndrome (PCOS) in 20%, and a significant increase in
      mean serum testosterone (p=0.046). A significant positive correlation existed
      between weight gain and the development of menstrual abnormalities (r=0.66,
      p<0.0001), hirsutism (r=0.53, p=0.006) and PCO (r=0.51, p=0.012). No correlation
      existed between weight change and serum reproductive hormonal changes. Yearly
      follow-up for next 2 years in some of these women revealed persistence of
      menstrual abnormalities, hirsutism and PCO, a significant linear increase in mean
      body weight, body mass index, and serum testosterone concentrations, and an
      increase in serum LH levels from second year onwards. LIMITATIONS: Limitations
      include small sample size and a high dropout rate on follow-up. CONCLUSIONS: Long
      term valproate therapy in Indian women with generalized epilepsy is associated
      with development of hirsutism, significant weight gain, stable or progressive
      alterations in reproductive hormonal function, and ultimately a higher occurrence
      of PCOS.

PMID- 17441995
TI  - Multivariate neuropsychological prediction of seizure lateralization in temporal
      epilepsy surgical cases.
AB  - PURPOSE: Neuropsychological assessment can be of assistance in determining
      seizure lateralization in cases where EEG and MRI findings do not provide clear
      lateralizing data. While several studies have examined the lateralizing value of
      individual neuropsychological measures, clinicians are still in need of a
      statistically sound method that permits the incorporation of multiple
      neuropsychological variables to predict seizure lateralization in the individual
      patient. METHOD: The present study investigated the lateralizing value of several
      commonly used neuropsychological measures in a large sample of patients (n = 217)
      who eventually underwent surgical resection to treat their epilepsy. Side of
      surgery was used to operationally define seizure lateralization. A comparison of
      the relative utility of a multivariate versus univariate approach to predict
      seizure lateralization was conducted in temporal epilepsy cases. RESULTS: The
      results provide evidence for the incremental validity of neuropsychological
      measures, other than memory and IQ tests, in the prediction of seizure
      lateralization in patients with medically intractable epilepsy. These data
      indicate that a multivariate approach increases the accuracy of prediction of
      seizure lateralization for temporal lobe epilepsy cases. CONCLUSION: This study
      supports the use of a multivariate approach using neuropsychological measures to
      predict seizure lateralization in temporal epilepsy surgical candidates.
      Regression formulas are provided to enhance the clinical utility of these
      findings.

PMID- 17441996
TI  - Panayiotopoulos syndrome: an important electroclinical example of benign
      childhood system epilepsy.
AB  - As a result of the converging evidence from multiple large independent studies,
      Panayiotopoulos syndrome (PS) is now formally recognized as a distinct clinical
      entity within the spectrum of benign focal epilepsies of childhood. Clinically,
      PS is manifested by predominantly autonomic seizures and electrographically with
      multifocal interictal spikes, while the few published ictal recordings have
      documented onsets of variable lobar topography. These typical electroclinical
      features do not allow straightforward assignment to a distinctive cortical area,
      rendering the term "focal"--as we currently understand it--problematic. This is a
      critical review of the clinical and EEG features of PS, focusing on those
      characteristics that may shed some light on its so far elusive pathophysiology.
      We also explore its electroclinical similarities to other idiopathic "focal"
      epilepsies and its differences to symptomatic focal epilepsies that may also
      manifest with autonomic ictal symptoms and signs. This methodology allows the
      formation of a rational hypothesis on the pathophysiology of PS that seems to be
      emerging as a good model for the so-called "system" (nonsymptomatic) epilepsies,
      with potentially important taxonomic implications.

PMID- 17441997
TI  - Posterior quadrantic epilepsy surgery: technical variants, surgical anatomy, and
      case series.
AB  - OBJECTIVE: Patients with intractable epilepsy due to extensive lesions involving
      the posterior quadrant (temporal, parietal, and occipital lobes) form a small
      subset of epilepsy surgery. This study was done with a view to analyze our
      experience with this group of patients and to define the changes in the surgical
      technique over the last 15 years. We also describe the microsurgical technique of
      the different surgical variants used, along with their functional neuroanatomy.
      METHODS: In this series there were 13 patients with a median age of 17 years. All
      patients had extensive presurgical evaluation that provided concordant evidence
      localizing the lesion and seizure focus to the posterior quadrant. The objective
      of the surgery was to eliminate the effect of the epileptogenic tissue and
      preserve motor and sensory functions. RESULTS: During the course of this study
      period of 15 years, the surgical procedure performed evolved toward incorporating
      more techniques of disconnection and minimizing resection. Three technical
      variants were thus utilized in this series, namely, (i) anatomical posterior
      quadrantectomy (APQ), (ii) functional posterior quadrantectomy (FPQ), and (iii)
      periinsular posterior quadrantectomy (PIPQ). After a median follow-up period of 6
      years, 12/13 patients had Engel's Class I seizure outcome. CONCLUSION: The
      results of surgery for posterior quadrantic epilepsy have yielded excellent
      seizure outcomes in 92% of the patients in the series with no mortality or major
      morbidity. The incorporation of disconnective techniques in multilobar surgery
      has maintained the excellent results obtained earlier with resective surgery.

PMID- 17441998
TI  - Intracarotid amobarbital procedure in post-temporal lobectomy patients.
AB  - We describe two patients who underwent intracarotid amobarbital procedure (IAP)
      postoperatively following temporal lobectomy (one right temporal and one left
      temporal lobectomy), prompted by consideration of reoperation for persistent,
      intractable seizures. IAP memory score, consisting of the percentage of correctly
      recognized dually encoded stimuli, was calculated for each hemisphere. Both
      patients performed well on the IAP baseline memory assessment prior to
      injections, and both were left hemisphere dominant for language. The IAP memory
      results were consistent with the postoperative neuropsychological memory
      evaluation in that the patient who had undergone nonlanguage-dominant temporal
      resection performed within normal limits, while the patient who had undergone
      language-dominant temporal resection performed poorly, although not completely
      amnestic, on memory testing. Injection of the nonsurgical, presumably healthy,
      hemisphere resulted in complete failure of memory in both patients, implying that
      baseline memory was dependent on the functional integrity of the nonsurgical
      hemisphere, inactivation of which led to complete memory disruption. Secondly,
      the hippocampus in the nonlanguage-dominant hemisphere was able to support memory
      to some extent, if not completely, when it functioned in isolation without the
      influence of the language-dominant hemisphere during the IAP. These findings are
      discussed in the context of functional reserve and adequacy models.

PMID- 17441999
TI  - The pharmacokinetics of antiepileptic drugs in rats: consequences for maintaining
      effective drug levels during prolonged drug administration in rat models of
      epilepsy.
AB  - Rodent models of chronic epilepsy with spontaneous recurrent seizures likely
      represent the closest parallel to the human condition. Such models may be best
      suited for therapy discovery for pharmacoresistant epilepsy and for
      antiepileptogenic or disease-modifying therapeutics. However, the use of such
      rodent models for therapy discovery creates problems with regard to maintaining
      effective drug levels throughout a prolonged testing period. This is particularly
      due to the fact that rodents such as rats and mice eliminate most drugs much more
      rapidly than humans. Thus, knowledge about elimination rate of a test drug in a
      laboratory species is essential for development of a treatment paradigm that
      allows maintaining adequate drug levels in the system over the period of
      treatment. Currently, the most popular models of epilepsy with spontaneous
      seizures are poststatus epilepticus models of temporal lobe epilepsy in rats.
      Such models are both used for studies on antiepileptogenesis and drug resistance.
      For validation of these models, current antiepileptic drugs (AEDs) have to be
      used. In this article, the elimination rates of these AEDs and their effective
      plasma levels in rats are reviewed as a guide for developing treatment protocols
      for chronic drug testing. The advantages and disadvantages of several
      technologies for drug delivery are discussed, and some examples for calculation
      of adequate treatment protocols are given. As shown in this review, because of
      the rapid elimination of most AEDs in rats, it is no trivial task to maintain
      effective steady-state AED levels in the plasma throughout the day over multiple
      days to ensure that there will be adequate levels in the system for the purpose
      of the experiment. However, the use of an adequate dosing regimen that is based
      on elimination rate is an absolute prerequisite when using rat models for
      discovery of new antiepileptogenic therapies or therapies for pharmacoresistant
      epilepsy, because otherwise such models may lead to erroneous conclusions about
      drug efficacy.

PMID- 17442000
TI  - The birth and evolution of the concept of Panayiotopoulos syndrome.

PMID- 17442001
TI  - Daily variation in an intracranial EEG feature in humans detected by a responsive
      neurostimulator system.
AB  - PURPOSE: Based on the observation that epileptic seizures can occur at specific
      times of the day, we looked for daily variation in an intracranial electrographic
      feature used by a responsive neurostimulator system to detect seizures. METHODS:
      A computationally efficient measure of intracranial EEG energy or complexity, the
      line length baseline, was calculated and reported by an external responsive
      neurostimulator during a clinical trial of device safety. Data were obtained from
      24 consecutive patients with medically intractable epilepsy undergoing
      intracranial monitoring over 2 to 54 days to localize the seizure onset zone.
      Measurements from individual subjects made at different times of day over many
      days were displayed on a single 24-h cycle and fit with a cosine function to
      characterize the time of the maximum value. The timing of epileptic seizures was
      also noted. RESULTS: The time of the maximum line length baseline value had a
      bimodal distribution with relative peaks at 05:30 and 15:00 hours. The time of
      the maximum value did not associate with specific brain regions, except that a
      nocturnal peak was not measured from temporal neocortex. The temporal
      distribution of maximum values was similar to the timing of epileptic seizures.
      CONCLUSION: The line length baseline feature of the intracranial EEG shows daily
      variation with location specific characteristics within individual subjects.

PMID- 17442002
TI  - Pharmacokinetics of levetiracetam in infants and young children with epilepsy.
AB  - PURPOSE: To assess the single-dose pharmacokinetics of levetiracetam and its
      major metabolite ucb L057 in infants and young children with epilepsy. METHODS:
      Eligible patients with a stable regimen of antiepileptic medications received a
      single oral dose of levetiracetam 20 mg/kg administered as a 10% oral solution
      followed by a 24-hour pharmacokinetic evaluation. RESULTS: Thirteen subjects (age
      2.3-46.2 months) enrolled and received levetiracetam; 12 provided evaluable
      pharmacokinetic data. Levetiracetam was rapidly absorbed and reached peak plasma
      concentration (t(max)) 1.4 +/- 0.9 hours after dosing. The mean half-life
      (t(1/2)) of levetiracetam was 5.3 +/- 1.3 hours, and the apparent clearance was
      1.46 +/- 0.42 mL/min/kg. Graphical differences were observed among three age
      subgroups (1 to <6 months, 6 to <24 months, and 24 to <48 months); however,
      statistical analysis was limited due to each subgroup's small sample size. No
      significant gender differences were detected. Treatment-emergent adverse events
      were seen in three patients (23.1%) but were not considered to be related to
      levetiracetam. CONCLUSIONS: The mean t(1/2) of levetiracetam was shorter and its
      apparent clearance was more rapid for infants and young children than that
      previously reported for adults. When determining dosage, age-dependent drug
      clearance should be considered; these findings suggest that a larger dose of
      levetiracetam (corrected for body weight) needs to be considered for infants and
      young children with epilepsy than that given to adults with epilepsy. A single
      dose of levetiracetam was well tolerated in this study population.

PMID- 17442003
TI  - Reduced hippocampal 5HT1A PET receptor binding and depression in temporal lobe
      epilepsy.
AB  - PURPOSE: To study the relation of hippocampal 5HT1A receptor binding to symptoms
      of depression in patients with temporal lobe epilepsy. Depression is common in
      people with epilepsy, and reduced 5HT1A binding has been reported in patients
      with primary depressive disorders. METHODS: We studied 45 patients with temporal
      lobe epilepsy confirmed by ictal video-EEG recording. Mood was assessed with the
      Beck Depression Inventory (BDI). Positron emission tomographic measurement of
      5HT1A receptors was performed with 18F-FCWAY, a highly specific silent
      antagonist. 3D-T1-weighted MRI was used to correct for structural atrophy.
      Receptor distribution volume (V) was corrected for plasma tracer free fraction
      (f1). RESULTS: There was a significant inverse relation between ipsilateral
      hippocampal v/f1 and the BDI. For contralateral hippocampus, there was a
      nonsignificant trend. Patients with BDI > 20 had significantly lower ipsilateral
      hippocampal V/f1 than patients in the low and medium groups. There was no
      significant effect of the presence of mesial temporal sclerosis, focus
      laterality, or gender on the BDI. CONCLUSIONS: Our study shows a relationship
      between hippocampal 5HT1A binding and depressive symptoms measured by the BDI in
      patients with epilepsy. The findings parallel results in patients with MDD.

PMID- 17442004
TI  - The association of MRI findings and neuropsychological functioning after the
      first recognized seizure.
AB  - PURPOSE: To explore relationships between MRI abnormalities of the brain and
      neuropsychological functioning in children who were evaluated following their
      first recognized seizure. METHODS: Subjects were children aged 6 to 14 years with
      a first recognized seizure within the past 3 months who participated in a larger
      prospective study of child adaptation. The 249 children with neuropsychological
      testing and neuroimaging were studied. Children underwent neuropsychological
      examination an average of 2.8 months and MRI examination an average of 1.3 months
      after the first recognized seizure. On factor analysis four factors were found
      for neuropsychological function: LANG = Language, PS = Processing Speed, EC =
      Executive/ Construction, VMEM = Verbal Memory and Learning. For analysis,
      structural abnormalities found on MRI were classified as significant (yes/no)
      based on whether they were presumed to be related to the seizure condition.
      RESULTS: On MRI, 34 (14%) had structural abnormalities that were judged to be
      significant in that they were possibly related to their seizures. Children with
      significant abnormalities had significantly lower estimated IQ scores and
      significantly lower language, processing speed, executive/constructional ability,
      and verbal memory and learning factor scores than did children without
      significant abnormalities. CONCLUSIONS: Children who have structural brain
      abnormalities at onset have slightly lower cognitive functioning overall, and all
      neuropsychological domains seemed to be affected relatively equally. This pattern
      was apparent even when we restricted the analysis to children with intellectual
      functioning in the broadly normal range.

PMID- 17442005
TI  - Autonomic status epilepticus in Panayiotopoulos syndrome and other childhood and
      adult epilepsies: a consensus view.
AB  - PURPOSE: To discuss and propose a definition of autonomic status epilepticus
      (SE), describe its clinical and EEG features, and review what is known about its
      epidemiology, pathophysiology, differential diagnosis, and management. METHODS:
      An international consortium of established researchers in the field was
      identified from their published work, agreed the purpose of the project, searched
      the literature, and, by use of e-mail communication, agreed the consensus
      document. RESULTS: Autonomic SE is a condition lasting at least 30 min and
      characterized by epileptic activity causing altered autonomic function of any
      type at seizure onset or in which manifestations consistent with altered
      autonomic function are prominent (quantitatively dominant or clinically
      important) even if not present at seizure onset. It is best described, and
      probably most commonly encountered in children, with Panayiotopoulos syndrome.
      However, it also occurs in children with symptomatic epilepsies and,
      exceptionally, in adults. Its pathogenesis and most appropriate management are
      poorly understood. CONCLUSIONS: It is hoped that this document will help clinical
      recognition of Autonomic SE, reduce misdiagnosis, and promote further interest
      and studies into what has been a relatively neglected area.

PMID- 17442006
TI  - Choosing a first drug treatment for epilepsy after SANAD: randomized controlled
      trials, systematic reviews, guidelines and treating patients.
AB  - The ILAE treatment guidelines for initial monotherapy emphasise the poor quality
      of information available to inform everyday clinical practice. Industry sponsored
      studies comparing antiepileptic drugs answer restricted licensing questions,
      rather than those relevant to the clinical community (patients, health
      professionals and founders of health care). The SANAD study, a pragmatic
      randomized clinical trial, offers a methodology to address some of these
      questions. It identifies lamotrigine as a cost-effective alternative to
      carbamazepine for the treatment of focal epilepsies, but confirms valproate as
      the most effective drug for the treatment of generalized or unclassified
      epilepsy.

PMID- 17442007
TI  - Panayiotopoulos syndrome: a prospective study of 192 patients.
AB  - OBJECTIVES: To characterize the electroclinical features and evolution of
      Panayiotopoulos Syndrome (PS). METHODS: Children with electroclinical criteria of
      PS were prospectively identified and followed-up clinically, and with sleep and
      awake EEGs between February 1990 and 2006. RESULTS: We identified 192 patients
      with PS. In the same length of time 398 children with benign childhood epilepsy
      with centro-temporal spikes (BCECTS) were registered. PS had a peak age at onset
      of 5 years. Autonomic manifestations were one of the most common ictal event.
      Ictal deviation of the eyes and progression to generalized convulsions were also
      quite frequent. Approximately one third had partial status epilepticus. In all
      patients except five, the seizures occurred during sleep. One-third also had fits
      while awake. Sixteen children had concomitant symptoms of rolandic epilepsy and
      eight developed rolandic seizures after remission of PS seizures. Prognosis was
      excellent. Eighty-four (44.2%) had a single seizure, 79 (41.2%) had 2-5 fits, and
      28 (14.6%) had frequent seizures. CONCLUSION: PS is less common than BCECTS, but
      is well defined and easily recognizable by clinical and EEG features, with
      autonomic manifestations as one of the most common ictal event.

PMID- 17442008
TI  - Decreased Efficacy of GABAA-receptor modulation by midazolam in the kainate model
      of temporal lobe epilepsy.
AB  - PURPOSE: The objective of this investigation was to characterize quantitatively
      the time-dependent changes in midazolam (MDL) efficacy in the silent period after
      induction of status epilepticus (SE) in rats. The changes in MDL efficacy were
      correlated to changes in ex vivo GABA(A)-receptor expression. METHODS: MDL
      efficacy was quantified by pharmacokinetic-pharmacodynamic (PK-PD) modeling by
      using the beta-frequency of the EEG as PD end point. Two PK-PD experiments were
      performed in each animal: the first experiment before and the second experiment
      at either day 4 or day 14 after SE. SE was induced by repetitive intraperitoneal
      injections with kainate. GABA(A)-receptor expression was determined by ex vivo
      autoradiography with [(3)H]flumazenil. RESULTS: The concentration versus EEG
      effect relation of midazolam was successfully described by the sigmoidal E(max)
      model. The maximal effect on the beta-frequency of the EEG (E(max)) was reduced
      to 51.6 +/- 35.6% and 25.8 +/- 33.7% of the original value at 4 and 14 days after
      induction of SE. The ex vivo study with [(3)H]flumazenil showed that the observed
      reductions in E(max) were paralleled by a reduction in GABA(A)-receptor density.
      CONCLUSIONS: The efficacy of MDL is decreased in the silent period after SE,
      which can be partly accounted for by a reduction in GABA(A)-receptor density.

PMID- 17442009
TI  - Proportional feedback stimulation for seizure control in rats.
AB  - PURPOSE: A responsive electrical brain stimulation system using control feedback
      was investigated for the treatment of seizures. METHODS: A proportional feedback
      stimulation system was designed. Penicillin-induced episodic seizures were
      created in rat primary motor cortex. Both intracranial (proximal to seizure
      focus) and extracranial EEGs were monitored. Current stimulation was applied at
      the seizure focus by using the intracranial EEG as the current-stimulus template.
      Different gains (H) for determining feedback stimulus amplitudes were tested.
      RESULTS: The effect of feedback stimulation on seizures was initially assessed by
      measuring change in variance of the amplitude histogram of the intracranial EEG
      before and during stimulation. Mean reduction in amplitude variance during
      seizure activity was significant, with variance during stimulation progressively
      reduced as feedback gain was increased, indicating that overall suppression of
      seizure amplitude depended on H. Further increases in feedback gain typically
      produced saturating oscillations, indicating that this level of H resulted in
      instability. Frequency analysis of seizure and stimulation periods for each of
      the effective levels of H demonstrated close correlation across a large frequency
      domain, suggesting that the reduction in EEG seizure amplitude during feedback
      stimulation was possibly because of shunting of neuronal currents near electrodes
      as opposed to an alteration of neuronal dynamics. Although the frequency and
      energy responses during seizures before or during feedback stimulation remained
      well correlated in the delta band, this correlation progressively decreased
      across the theta, alpha, and beta bands. CONCLUSIONS: These results demonstrate
      that proportional feedback stimulation holds the promise of suppressing seizure
      activity. More-complicated control algorithms for generating feedback stimulation
      may provide further improvements in seizure suppression.

PMID- 17442010
TI  - Long-term prognosis for symptomatic (secondarily) generalized epilepsies: a
      population-based study.
AB  - PURPOSE: To describe the long-term outcome of childhood-onset secondarily
      generalized epilepsies (SGEs). METHODS: Children were identified from the Nova
      Scotia population-based epilepsy study (n=692). Onset of epilepsy was between
      1977 and 1985, and follow-up was mainly in 2003. SGE was defined as having a
      mixture of more than one generalized seizure types including myoclonus,
      akinetic/atonic, tonic, or atypical absence, plus an interictal EEG with
      generalized spike-wave (irregular or slow) and/or multifocal spikes. RESULTS: SGE
      was identified in 80 children, 11.6% (80 of 692) of all childhood epilepsy. Forty
      percent did not fit into a currently accepted syndrome (such as Lennox-Gastaut,
      myoclonic-astatic or West). Seizure onset was in the first year of life in 60%,
      with only 9% later free of intellectual or physical handicap. Sixty-five percent
      (11 of 17) with Lennox-Gastaut had preceding West syndrome. During a median
      follow-up of 20 years, mortality was 24% (n=19), and 53% (n=42) had persistently
      intractable seizures. Surprisingly, 22 (28%) had >or=5 years of terminal
      remission (West, 31%, 10 of 32; Lennox-Gastaut, 0, none of four; myoclonic
      astatic, 56%, five of nine; undefined, 31%, 10 of 32). At the end of follow-up,
      nearly 90% of patients fell into one of three outcome categories: death, 19
      (24%); alive with intractable epilepsy, 31 (39%); or in remission for >or=5
      years, 21 (26%). CONCLUSIONS: Many children with SGE have ill-defined epilepsy
      syndromes. SGE is characterized by early age at onset, high rates of handicap,
      intractability, and death, although one third achieve complete seizure control
      with a long terminal remission.

PMID- 17442011
TI  - Impact of mandatory physician reporting on accident risk in epilepsy.
AB  - BACKGROUND: In some jurisdictions, physicians are required by law to report
      patients with seizures to the department of motor vehicles. We assessed the
      hypothesis that mandatory reporting reduces the risk of automobile accidents in
      people with epilepsy. METHODS: A retrospective survey of driving and accident
      rates was done by mailed questionnaire to two groups of subjects with epilepsy in
      Canada, one living in Ontario where reporting is mandatory and the other in
      Alberta where it is not. Responses were obtained from a control group without
      epilepsy for comparison. RESULTS: The epilepsy (n = 425) and control (n = 375)
      groups were comparable in age and sex. Seventy-three percent of the epilepsy
      group were or had been licensed drivers compared to 94% of the controls (rr 0.77,
      95% CI 0.73-0.83, p < 0.001). Lifetime accident rate of licensed drivers was 58%
      in epilepsy and 60% in controls (rr 0.99, 95%CI 0.82-1.19, ns) while 9% of the
      epilepsy group and 9% of the controls had an accident in the previous year (rr
      1.00, 95%CI 0.95-1.06, ns). All those with epilepsy in Ontario (n = 202) and
      Alberta (n = 223), also comparable in age and sex, had equal lifetime accident
      rates of 45 and 46% (rr 0.99, 95%CI 0.67-1.47, ns) and 1-year rates of 11 and 8%
      (rr 1.38, 95%CI 0.59-3.27, ns). In Ontario, 20% of drivers were unlicensed
      compared to 9% in Alberta (rr 2.39, 95%CI 1.17-4.89, p = 0.01) CONCLUSION:
      Although it is clearly dangerous for many people with ongoing seizures to drive,
      the findings provide no support for the hypothesis that mandatory reporting of
      patients by physicians reduces accident risk and suggest that concerns about the
      impact of epilepsy on driving compared to other medical and nonmedical risk
      factors may be excessive.

PMID- 17442012
TI  - Proposal of an algorithm for diagnosis and treatment of neonatal seizures in
      developing countries.
AB  - Seizures in the neonatal period are common. They can be caused by a variety of
      conditions, ranging from benign, self-limited illnesses to severe, life
      threatening disorders. They are often the first sign of neurologic dysfunction in
      neonates, and may be used as one factor in considering long-term prognosis. An
      important mission of the International League Against Epilepsy (ILAE) is to
      improve the care of patients with epilepsy. Most recently, as part of the Global
      Campaign against Epilepsy, ILAE, in conjunction with the World Health
      Organization (WHO), established a new initiative to create clinical guidelines
      and diagnostic and management algorithms for the care of patients with seizures
      that can be applied worldwide, including in developing countries with limited or
      varied medical resources. Created by an international panel of experts in seizure
      management and guideline development, this document proposes guidelines for the
      diagnosis and management of the most common and important conditions that cause
      seizures in the neonatal period. The publication of these clinical pathways for
      neonatal seizures will be followed by a period of field testing and comment by
      WHO clinicians and officials before finalization.

PMID- 17442013
TI  - Response of soil microbial biomass and community structures to conventional and
      organic farming systems under identical crop rotations.
AB  - In this study the influence of different farming systems on microbial community
      structure was analyzed using soil samples from the DOK long-term field experiment
      in Switzerland, which comprises organic (BIODYN and BIOORG) and conventional
      (CONFYM and CONMIN) farming systems as well as an unfertilized control (NOFERT).
      We examined microbial communities in winter wheat plots at two different points
      in the crop rotation (after potatoes and after maize). Employing extended polar
      lipid analysis up to 244 different phospholipid fatty acids (PLFA) and
      phospholipid ether lipids (PLEL) were detected. Higher concentrations of PLFA and
      PLEL in BIODYN and BIOORG indicated a significant influence of organic
      agriculture on microbial biomass. Farmyard manure (FYM) application consistently
      revealed the strongest, and the preceding crop the weakest, influence on domain
      specific biomass, diversity indices and microbial community structures.
      Esterlinked PLFA from slowly growing bacteria (k-strategists) showed the
      strongest responses to long-term organic fertilization. Although the highest
      fungal biomass was found in the two organic systems of the DOK field trial, their
      contribution to the differentiation of community structures according to the
      management regime was relatively low. Prokaryotic communities responded most
      strongly to either conventional or organic farming management.

PMID- 17442014
TI  - Progress in vaccine development against Helicobacter pylori.
AB  - Based on the very high prevalence of diseases caused by Helicobacter pylori,
      particularly in the developing world, and the rapid emergence of antibiotic
      resistance among clinical isolates, there is a strong rationale for an effective
      vaccine against H. pylori. In this review we describe recent promising candidate
      vaccines and prophylactic or therapeutic immunization strategies for use against
      H. pylori, as well as studies to identify immune responses that are related to
      protection in experimental animals. We also describe identification of different
      types of immune responses that may be related to protection against symptoms
      based on comparisons of H. pylori-infected patients with duodenal ulcers or
      gastric cancer and asymptomatic carriers. We conclude that there is still a
      strong need to clarify the main protective immune mechanisms against H. pylori as
      well as to identify a cocktail of strong protective antigens, or recombinant
      bacterial strains that express such antigens, that could be administered by a
      regimen that gives rise to effective immune responses in humans.

PMID- 17442015
TI  - Variability of the 16S-23S rRNA gene internal transcribed spacer in Pseudomonas
      avellanae strains.
AB  - The 16S-23S rRNA gene internal transcribed spacer region (ITS1) from 34 strains
      of Pseudomonas avellanae and some strains of Pseudomonas syringae pathovars was
      amplified and assessed by restriction fragment length polymorphism (RFLP) using
      10 restriction enzymes. In addition, the ITS1 region of four representative P.
      avellanae strains was sequenced and compared by the neighbour-joining algorithm
      with that of P. syringae pathovars. Two main groups of P. avellanae strains were
      observed that did not correlate with their origin. The ITS1 region sequencing
      revealed a high similarity with the P. syringae complex. One group of P.
      avellanae strains showed high similarity to P. s. pv. actinidiae and P. s. pv.
      tomato; another group showed similarity with P. s. pv. tabaci and P. s. pv.
      glycinea. Two strains clustered with P. s. pv. pisi. The difficulties to
      unambiguously classify the strains associated with hazelnut decline in Greece and
      Italy are discussed.

PMID- 17442016
TI  - Solving ambiguities in contig assembly of Idiomarina loihiensis L2TR chromosome
      by in silico analyses.
AB  - Nucleotide composition analyses of bacterial genomes such as cumulative GC skew
      highlight the atypical, strongly asymmetric architecture of the recently
      published chromosome of Idiomarina loihiensis L2TR, suggesting that an inversion
      of a 600-kb chromosomal segment occurred. The presence of 3.4-kb inverted
      repeated sequences at the borders of the putative rearrangement supports this
      hypothesis. Reverting in silico this segment restores (1) a symmetric chromosome
      architecture; (2) the co-orientation of transcription of all rRNA operons with
      DNA replication; and (3) a better conservation of gene order between this
      chromosome and other gamma-proteobacterial ones. Finally, long-range PCRs
      encompassing the ends of the 600-kb segment reveal the existence of the reverted
      configuration but not of the published one. This demonstrates how cumulative
      nucleotide-skew analyses can validate genome assemblies.

PMID- 17442017
TI  - Passive ultrasonic irrigation of the root canal: a review of the literature.
AB  - Ultrasonic irrigation of the root canal can be performed with or without
      simultaneous ultrasonic instrumentation. When canal shaping is not undertaken the
      term passive ultrasonic irrigation (PUI) can be used to describe the technique.
      In this paper the relevant literature on PUI is reviewed from a MEDLINE database
      search. Passive ultrasonic irrigation can be performed with a small file or
      smooth wire (size 10-20) oscillating freely in the root canal to induce powerful
      acoustic microstreaming. PUI can be an important supplement for cleaning the root
      canal system and, compared with traditional syringe irrigation, it removes more
      organic tissue, planktonic bacteria and dentine debris from the root canal. PUI
      is more efficient in cleaning canals than ultrasonic irrigation with simultaneous
      ultrasonic instrumentation. PUI can be effective in curved canals and a smooth
      wire can be as effective as a cutting K-file. The taper and the diameter of the
      root canal were found to be important parameters in determining the efficacies of
      dentine debris removal. Irrigation with sodium hypochlorite is more effective
      than with water and ultrasonic irrigation is more effective than sonic irrigation
      in the removal of dentine debris from the root canal. The role of cavitation
      during PUI remains inconclusive. No detailed information is available on the
      influence of the irrigation time, the volume of the irrigant, the penetration
      depth of the instrument and the shape and material properties of the instrument.
      The influence of irrigation frequency and intensity on the streaming pattern as
      well as the complicated interaction of acoustic streaming with the adherent
      biofilm needs to be clarified to reveal the underlying physical mechanisms of
      PUI.

PMID- 17442018
TI  - Persistence of human papillomavirus as a predictor for treatment failure after
      loop electrosurgical excision procedure.
AB  - We aimed to investigate whether postconization human papillomavirus (HPV) DNA
      testing can predict treatment failure and improve the accuracy of conventional
      follow-up in women with high-grade cervical intraepithelial neoplasia (CIN).
      Between March 2001 and October 2005, 120 patients with confirmed CIN 2 or 3 were
      treated with loop electrosurgical excision procedure (LEEP) and were enrolled.
      Six patients were lost to the follow-up. Postconization follow-up was performed
      at every 3-6 months during the first year and then annually. Specimens were
      tested for the presence of HPV, using the Hybrid Capture 2 (Digene Co,
      Gaithersburg, MD) and HPV DNA chip (Mygene Co, Seoul, Korea) test. Persistent HPV
      infection was defined as persistently (two times or more) positive HPV tests with
      the same HPV subtype(s) at initial diagnosis. Twenty-two (19.3%) patients showed
      treatment failure after conization. The only significant risk factor for
      redevelopment of CIN after conization was persistence of the same HPV subtype (P
      < 0.0001). And women with recurrent or residual CIN had higher HPV load during
      the 6-month follow-up postconization. In conclusion, the persistence of the same
      HPV subtype after LEEP conization was an important predictor of treatment
      failure. The follow-up protocol after conization of CIN should include both
      cervical cytology and HPV test, and HPV DNA chip test is needed to detect a
      persistent HPV infection.

PMID- 17442019
TI  - The relationship between human papillomavirus infection and cervical
      intraepithelial neoplasia in Turkish women.
AB  - To compare the prevalence of cervical human papillomavirus (HPV) infection in
      Turkish women with normal Papanicolaou (Pap) smear and cervical intraepithelial
      neoplasia (CIN). In between March 2002 and November 2005, the study was designed
      as case-control study. Cytologic abnormalities in Pap smears were classified
      according to the Bethesda System (2001). Identification of the presence of HPV
      was carried out by the Hybrid Capture II test for all patients. To compare the
      groups, Chi-square test was used. A total of 1353 reproductive aged women were
      screened. Of them, 1344 (99.3%) had normal or class I Pap smear. Remaining nine
      cases (0.7%) had CIN at several degrees (five CIN I, three CIN II, and one
      carcinoma in situ). While all these nine cases with cervical pathologies had HPV,
      only 20 cases from the other group (1.5%) had HPV (chi(2) 466.1; P = 0.0001).
      This is the first study of the evaluation of the association between HPV and
      preinvasive cervical lesions in Turkish population. In spite of low general
      frequency (2.1%) of cervical HPV colonization in this population, a strong
      correlation was found between HPV and CIN.

PMID- 17442020
TI  - Expression of vascular endothelial growth factor and assessment of microvascular
      density with CD 34 and endoglin in proliferative endometrium, endometrial
      hyperplasia, and endometrial carcinoma.
AB  - The aim of this study was to compare vascular endothelial growth factor (VEGF),
      CD 34, and endoglin expressions as markers of angiogenesis in proliferative
      endometrium (PE), endometrial hyperplasia (EH), and endometrial carcinoma (EC)
      and to find the possible impact of angiogenesis on malign transformation.
      Formalin-fixed, paraffin-embedded tissues from 12 patients with PE, 23 patients
      with simple EH and complex EH with atypia, and 31 patients with EC were included.
      A semiquantitative scoring system was used to assess the intensity and degree of
      staining of VEGF. Microvessel density (MVD) was assessed with endoglin and anti
      CD 34 in most vascular areas. VEGF expression was significantly higher in EC and
      EH than PE, but there was no difference between EC and EH. According to CD 34
      staining, there were no differences in MVD between groups. However, mean MVD
      counts assessed by endoglin were significantly higher in EC than PE and EH.
      Although VEGF expression in EC was significantly higher, it did not correlate
      with other measures of angiogenesis. MVD using endoglin seemed to reflect
      neoplastic angiogenesis better than CD 34.

PMID- 17442021
TI  - Prognostic factors associated with brain metastases from epithelial ovarian
      carcinoma.
AB  - Brain metastasis from epithelial ovarian carcinoma (EOC) is managed by a
      multimodal treatment approach. Thus, to determine the prognostic factors
      associated with this situation is important for management decisions regarding
      the type of treatment and aggressiveness of treatment. From 1995 to 2005, 13
      patients with brain metastases resulting from EOC underwent treatment at Samsung
      Medical Center. We retrospectively reviewed the medical records to determine
      prognostic factors and to evaluate treatment outcome. The median age at diagnosis
      for primary ovarian carcinoma and brain metastasis was 52 and 55 years,
      respectively. Median interval to brain metastases was 28 months after the
      diagnosis of EOC. At the time of analysis, nine patients had died of disease. The
      median survival from brain relapse was 7 months. A Karnofsky performance status
      of 70 or higher, primary control, solitary brain lesions, recursive partitioning
      analysis (RPA) class, and treatment modality including gamma-knife radiosurgery
      (GKRS) were related to survival on univariate analyses. Multivariate analysis
      showed that treatment modality including GKRS was a more important prognostic
      factor than RPA class (P = 0.04). This small series demonstrated that GKRS can be
      a valuable modality for the management of brain metastasis in patients with EOC.
      Therefore, a better outcome can be achieved by choosing GKRS in their treatments
      in selected patients.

PMID- 17442022
TI  - Hormone therapy in advanced and recurrent endometrial cancer: a systematic
      review.
AB  - Endometrial cancer is a hormone-dependent malignancy, and the majority has a
      precursor phase of endometrial hyperplasia. Histologic subtypes have been
      recognized with differing natural history. The relationship between hormone
      response, histology, and molecular profile is not established, but the relevant
      biology is summarized. This study was a systematic review of the literature to
      identify which populations should be considered for hormone interventions.
      Systematic searches were carried out in the English literature for randomized
      controlled trials and phase II studies of hormone interventions in endometrial
      cancer. Five randomized trials and 29 phase II studies were identified comprising
      a total of 2471 patients. In previously untreated patients with grade 1 (G1) or
      G2 tumors, the response rate for progestogens and the progression-free survival
      is in the range of 11-56% and 2.5-14 months, respectively. Higher response rates
      are seen in progesterone receptor-positive cases. Phase II studies comprise the
      majority of the data and many are of poor quality. There was considerable
      heterogeneity in patient selection, prior treatment, and type of regimen, and
      meta-analysis was not possible. G3 or G4 toxicity was less than 5%. We conclude
      that hormone receptor assessments should be carried out in all patients entered
      on clinical trials and may aid clinical management in selected cases. Receptor
      negative status should not be an absolute contraindication to hormone
      intervention. Integration of hormone treatment with conventional chemotherapy and
      growth factor-targeted therapy needs to be explored.

PMID- 17442024
TI  - Dietary acculturation and diet quality of hypertensive Korean Americans.
AB  - AIM: This paper is a report of a study to describe the dietary acculturation of
      hypertensive and normotensive Korean Americans and native Koreans by comparing
      dietary pattern and diet quality. BACKGROUND: Dietary acculturation is a major
      factor that influences the risks for cardiovascular disease in immigrants. Nurses
      play a key role in educating immigrants about dietary acculturation. Limited
      studies have examined dietary acculturation of Korean immigrants with
      hypertension. METHOD: A descriptive study of hypertensive and normotensive Korean
      Americans and native Koreans (n = 398) was conducted in 2003-04, using the 24
      hour dietary recall method. Dietary pattern was measured by consumption frequency
      of Korean, American and common food, and eating outside the home. Diet quality
      was measured by the revised version of the Diet Quality Index. FINDINGS: Korean
      Americans showed greater consumption of American food, common food and fast food,
      and ate away from home more often than native Koreans. Overall Diet Quality Index
      scores were not statistically significantly different between the two groups
      after matching. Compared with native Koreans, Korean Americans consumed lower
      amounts of sodium, potassium, vegetables and fruits, and energy from
      carbohydrates. Hypertensive Korean Americans consumed fewer vegetables and
      fruits, and less sodium and potassium than hypertensive native Koreans. No
      statistically significant differences were found between hypertensive and
      normotensive Korean Americans in dietary acculturation. CONCLUSION: Dietary
      acculturation of immigrants is a common phenomenon regardless of the country from
      which they immigrate. Healthcare professionals should consider the advantages and
      disadvantages of dietary acculturation in health promotion for immigrants.

PMID- 17442023
TI  - Autoantibody profile in the experimental model of scleroderma induced by type V
      human collagen.
AB  - The aim of this study is to evaluate the humoral autoimmune response in the
      experimental model of systemic sclerosis (SSc) induced by human type V collagen
      (huCol V). New Zealand rabbits were immunized with huCol V in Freund's complete
      adjuvant (FCA) and boosted twice with 15 days intervals with huCol V in Freund's
      incomplete adjuvant. Control groups included animals injected only with FCA or
      bovine serum albumin. Bleeding was done at days 0, 30, 75 and 120. Tissue
      specimens were obtained for histopathological investigation. Serological analysis
      included detection of antibodies against huCol V and anti-topoisomerase I (Anti
      Scl70) by enzyme-linked immunosorbent assay, antinuclear antibodies (ANA) by
      indirect immunofluorescence, and rheumatoid factor (RF) by a latex agglutination
      test. Target antigens were characterized by immunoblot. Histological analysis
      revealed extracellular matrix remodeling with fibrosis and vasculitis. Anti-Scl70
      and ANA were detected as early as 30 days in all huCol V animals. The universal
      ANA staining pattern was Golgi-like. This serum reactivity was not abolished by
      previous absorption with huCol V. Characterization of the target antigen by
      immunoblot revealed two major protein fractions of 175,000 and 220,000 MW.
      Similarly to ANA, there was a gradual increase of reactivity throughout the
      immunization and also it was not abolished by preincubation of serum samples with
      huCol V. RF testing was negative in hyperimmune sera. CONCLUSION: The production
      of autoantibodies, including anti-Scl70, a serological marker for SSc associated
      with histopathological alterations, validates huCol V induced-experimental model
      and brings out its potential for understanding the pathophysiology of SSc.

PMID- 17442025
TI  - The impact of social factors on tuberculosis management.
AB  - AIM: This paper is a report of a study to examine the impact of social factors on
      the management of tuberculosis including engagement with services,
      hospitalization and extended treatment. BACKGROUND: Rates of tuberculosis in
      major European cities have increased greatly in the last 10 years. The changing
      epidemiology of the disease, concentrated in marginalized groups, presents new
      challenges to the control of tuberculosis. METHODS: A prospective cohort study of
      250 newly diagnosed tuberculosis patients was conducted in London between January
      2003 and January 2005. Data were collected by means of a risk assessment tool and
      from medical records. Outcome measures included missed appointments, frequency
      and duration of hospitalization and length of treatment. RESULTS: The median age
      of the study sample was 33.82 (range 16.4-92.5) and 56.8% were male. Thirty-two
      per cent were hostel/street homeless or temporarily sharing accommodation with
      friends or relatives. Thirty-nine per cent were in receipt of welfare benefits
      and 13.2% had no income. Over a third anticipated difficulties taking their
      medicines and 30.3% had noone to remind them of this. Increased hospitalization
      was associated with hostel/street homelessness, drug or alcohol use and having
      noone to remind them to take their medicines (all P <or= 0.01). Missed
      appointments were associated with drug/alcohol use and previous tuberculosis
      treatment. Extended treatment was also associated with drug/alcohol use; previous
      tuberculosis treatment, drug resistance and those anticipating difficulties
      taking medication (all P <or= 0.001). CONCLUSIONS: The development of a social
      outreach model of care with an emphasis on prevention and support is an essential
      aspect of modern, international tuberculosis care.

PMID- 17442026
TI  - Distinguishing between task and contextual performance for nurses: development of
      a job performance scale.
AB  - AIM: This paper is a report of a development and validation of a new job
      performance scale based on an established job performance model. BACKGROUND:
      Previous measures of nursing quality are atheoretical and fail to incorporate the
      complete range of behaviours performed. Thus, an up-to-date measure of job
      performance is required for assessing nursing quality. METHODS: Test construction
      involved systematic generation of test items using focus groups, a literature
      review, and an expert review of test items. A pilot study was conducted to
      determine the multidimensional nature of the taxonomy and its psychometric
      properties. All data were collected in 2005. FINDINGS: The final version of the
      nursing performance taxonomy included 41 behaviours across eight dimensions of
      job performance. Results from preliminary psychometric investigations suggest
      that the nursing performance scale has good internal consistency, good convergent
      validity and good criterion validity. CONCLUSION: The findings give preliminary
      support for a new job performance scale as a reliable and valid tool for
      assessing nursing quality. However, further research using a larger sample and
      nurses from a broader geographical region is required to cross-validate the
      measure. This scale may be used to guide hospital managers regarding the quality
      of nursing care within units and to guide future research in the area.

PMID- 17442027
TI  - Improving the clinical usefulness of a behavioural pain scale for older people
      with dementia.
AB  - AIM: This paper is a description of the process of item reduction as part of the
      construction of the Pain Assessment Checklist for Seniors with Limited Ability to
      Communicate to assess pain in Dutch older nursing home residents with dementia.
      BACKGROUND: A valid and reliable clinically useful tool is important for
      assessing pain in people with dementia. The Pain Assessment Checklist for Seniors
      with Limited Ability to Communicate has demonstrated good inter- and intra-rater
      reliability and evidence of construct validity. However, nurses found the scale
      too long for clinical use. METHODS: In an observational study in 2005, nursing
      home patients (n = 128) were observed while receiving an influenza injection, and
      a selection of patients were also assessed at a patient-specific pain moment.
      Internal consistency and Principal Component Analysis were used to refine the
      scale, to examine the psychometric quality and underlying factor structure of the
      scale. RESULTS: A brief and manageable version of the Pain Assessment Checklist
      for Seniors with Limited Ability to Communicate in Dutch was developed, with a
      three-component solution including 24 items. This version had high levels of
      internal consistency for the complete scale (Cronbach's alpha range 0.82-0.86)
      and for all subscales (alpha range 0.72-0.82). Social-emotional items played a
      significant role in detecting pain. CONCLUSION: It is important to have a valid,
      reliable, brief and manageable pain scale available for the nursing home setting.
      Further research is needed to examine the adequacy and effectiveness of the scale
      in daily clinical practice.

PMID- 17442028
TI  - Factors facilitating and inhibiting evidence-based nursing in Iran.
AB  - AIM: This paper is a presentation of a study to clarify the concept of evidence
      based nursing and to explore the factors that influence evidence-based nursing by
      Iranian nurses. BACKGROUND: Evidence-based practice was introduced as an approach
      to high-quality care intended to improve results for patients. Several nurse
      researchers have studied factors affecting implementation of evidence-based
      nursing in western countries. However, there is little or no research on the
      perceptions of evidence-based nursing and its barriers in eastern countries,
      especially Iran. METHODOLOGY: Grounded theory method was used. Interviews with 21
      participants and 30 hours of observation were conducted in hospitals in Iran
      during 2005. Constant comparative analysis was used to analyse the data.
      FINDINGS: Two main categories, 'the meaning of evidence-based nursing', and
      'factors affecting it', emerged from the data. From participants' perspectives,
      evidence-based nursing was defined as 'caring for patients based on the nurse's
      professional knowledge in meeting patients' needs'. The second category, factors
      affecting evidence-based care, had six subcategories: possessing professional
      knowledge and experience; having time and opportunity; becoming accustomed; self
      confidence; the process of nursing education; and the work environment and its
      expectations. CONCLUSION: Managers and educators need to be committed to the
      principles of EBP, provide resources and create a supportive environment for its
      implementation. Individual nurses also have a responsibility to carry out
      evidence-based nursing, and researchers should work with practitioners to
      generate high quality evidence to support nursing practice.

PMID- 17442029
TI  - The development and validation of the On-the-job Learning Styles Questionnaire
      for the Nursing Profession.
AB  - AIM: This paper is a report of a study to develop and test the psychometric
      properties of the On-the-job Learning Style Questionnaire for the Nursing
      Profession. BACKGROUND: Although numerous questionnaires measuring learning
      styles have been developed, none are suitable for working environments. Existing
      instruments do not meet the requirements for use in workplace settings and tend
      to ignore the influence of different learning situations. METHOD: The
      questionnaire was constructed using a situation-response design, measuring
      learning activities in different on-the-job learning situations. Content validity
      was ensured by basing the questionnaire on interview studies. The questionnaire
      was distributed to 912 Registered Nurses working in different departments of 13
      general hospitals in the Netherlands at the end of 2005. FINDINGS: The response
      rate was 41% (372 questionnaires). The internal factor structure of the
      questionnaire was partly based on the learning activities in which nurses
      participate and partly on the learning situation in which they are performed. The
      internal consistency was good. The situation-response design of the questionnaire
      demonstrated its added value. Construct validity was estimated using
      intercorrelations between the scales, and criterion validity was estimated based
      on the relationships of the scales with perceived professional competence.
      CONCLUSION: The On-the-job Learning Styles Questionnaire for the Nursing
      Profession is well suited to describing nurses' learning styles in on-the-job
      settings and has satisfactory psychometric properties.

PMID- 17442030
TI  - Caring for a relative with dementia: family caregiver burden.
AB  - AIM: This paper is a report of part of a study to investigate the burden
      experienced by families giving care to a relative with dementia, the consequences
      of care for the mental health of the primary caregiver and the strategies
      families use to cope with the care giving stressors. BACKGROUND: The cost of
      caring for people with dementia is enormous, both monetary and psychological.
      Partners, relatives and friends who take care of patients experience emotional,
      physical and financial stress, and care giving demands are central to decisions
      on patient institutionalization. METHOD: A volunteer sample of 172 caregiver/care
      recipient dyads participated in the study in Cyprus in 2004-2005. All patients
      were suffering from probable Alzheimer's type dementia and were recruited from
      neurology clinics. Data were collected using the Memory and Behaviour Problem
      Checklist, Burden Interview, Center for Epidemiological Studies-Depression scale
      and Ways of Coping Questionnaire. FINDINGS: The results showed that 68.02% of
      caregivers were highly burdened and 65% exhibited depressive symptoms. Burden was
      related to patient psychopathology and caregiver sex, income and level of
      education. There was no statistically significant difference in level of burden
      or depression when patients lived in the community or in institutions. High
      scores in the burden scale were associated with use of emotional-focused coping
      strategies, while less burdened relatives used more problem-solving approaches to
      care-giving demands. CONCLUSION: Caregivers, especially women, need
      individualized, specific training in how to understand and manage the behaviour
      of relatives with dementia and how to cope with their own feelings.

PMID- 17442031
TI  - Against the odds: experiences of nurse leaders in Clinical Development Units
      (Nursing) in Australia.
AB  - AIM: This paper is a report of a longitudinal study to develop an understanding
      of the phenomena of Clinical Development Unit (Nursing) leadership by exploring
      the experiences of the nurse leaders of nine Australian units as they attempted
      to develop their existing wards or units into recognized centres of nursing
      excellence. BACKGROUND: The concept of Clinical Development Unit (Nursing) in
      Australia originated in the British Nursing Development Unit movement, which has
      been widely credited with introducing innovative approaches to developing nurses
      and nursing. A network of nine Clinical Development Units (Nursing) was set up in
      a suburban area health service in Australia. The aim was to develop existing
      wards or units into centres of excellence by disseminating a new vision for
      Australian nurses that was based on the pioneering work of the British Nursing
      Development Unit movement. METHODOLOGY: Principles of Heideggerian hermeneutic
      phenomenology provided a framework for the study. Nine Clinical Development Unit
      (Nursing) leaders participated in qualitative interviews from 1998 to 2002. These
      interviews were transcribed into text and thematically analysed. FINDINGS:
      Despite attempts to implement a variety of measures to nurture these Clinical
      Development Units (Nursing) until they had become well established, the new
      Clinical Development Unit (Nursing) leaders were unable to maintain the Clinical
      Development Unit (Nursing) vision with which they had been entrusted. This paper
      discusses their reactions to the problems they faced and the new understandings
      they developed of their Clinical Development Unit (Nursing) role over time.
      CONCLUSION: The findings illuminate the difficulties involved in maintaining the
      commitment of all levels of staff and management when attempting to introduce new
      nursing projects.

PMID- 17442032
TI  - Home visiting programme for older people with health problems: process
      evaluation.
AB  - AIM: This paper is a report of a process evaluation of the content, patient
      compliance and participant experiences of a home visiting programme for older
      people with self-reported health problems. BACKGROUND: Systematic home visits by
      nurses to older people are a public health strategy to improve their functional
      abilities and prevent institutionalization. Evidence of the usefulness of these
      visits is conflicting, partly due to a lack of information on the intervention
      process in these programmes. METHOD: One hundred and sixty people (aged 70-84
      years) participated in the programme and were visited eight times during an 18
      month period (February 2003-October 2004) by experienced home nurses. The nurses
      recorded key elements of each visit on standard forms: topics discussed,
      interventions regarding health problems and risks, and compliance with these
      interventions. Participants' and nurses' opinions on the visits were obtained
      through interviews at the end of the programme. FINDINGS: Nearly 80% of the group
      received the complete programme. Problems were detected in nearly all visits,
      mainly regarding social and psychological functioning, circulatory and
      musculoskeletal problems, and vision or hearing impairment. On average, ten
      problems and 11 interventions were recorded per participant. Nearly 40% of
      interventions related to referrals, 45% to advice and 17% consisted of
      information-giving. The compliance rate was 65% for referrals and 58% for advice.
      Both nurses and participants were positive about the programme. CONCLUSION: A
      health visiting programme, performed by home nurses, is feasible and appreciated
      by frail elders. The latter seem to be a relevant target population in view of
      the many and varied problems detected.

PMID- 17442033
TI  - A model of job satisfaction of nurses: a reflection of nurses' working lives in
      Mainland China.
AB  - AIM: This paper is a report of a study exploring nurses' views and experience
      regarding their working lives in Mainland China. BACKGROUND: The widespread
      nursing shortage and high turnover has become a global issue. Job satisfaction
      among nurses is a key factor in nurse turnover. Although several models of job
      satisfaction have been suggested in Western countries, these require further
      development and testing in Mainland China, where the social context of the labour
      market is different. METHOD: A survey design using questionnaires was adopted. A
      total of 512 hospital nurses in Beijing participated in the study in 2004,
      representing a response rate of 81%. FINDINGS: There was a negative relationship
      between nurses' job satisfaction and intention to leave their current hospitals,
      which was mediated by age (P < 0.05). About 40% of the variance in job
      satisfaction could be explained by the set of independent variables including
      organizational commitment, occupational stress, professional commitment, role
      conflict, role ambiguity, educational level, age and working years (R2 = 0.396).
      Organizational commitment had the strongest impact on job satisfaction, which
      explained 31.3% of the variance in this, followed by occupational stress and role
      conflict (5.5% and 1.9% respectively). In addition, both nurses' role perception
      and actual role content influenced job satisfaction as well as occupational
      stress, role conflict and role ambiguity (P < 0.05). Nurses' educational level
      was also a factor related to role perception, professional commitment and role
      conflict (P < 0.05). CONCLUSION: Nurses' job satisfaction could be increased
      through promoting organizational and professional commitment and reducing
      occupational stress, role conflict and role ambiguity.

PMID- 17442034
TI  - Use of complementary and alternative medicine among people living with diabetes:
      literature review.
AB  - AIM: This paper is a report of a literature review to explore the prevalence of
      complementary and alternative medicine use amongst people with diabetes to inform
      nursing practice, education and research. BACKGROUND: Diabetes mellitus affects
      the entirety of a person's being and increasingly people use complementary and
      alternative medicine in conjunction with other medical treatments and lifestyle
      modifications to manage their condition and improve well-being. METHODS: The
      CINAHL, Medline, ProQuest nursing journals and Psych INFO databases were searched
      for the period 1990-2006 using identified keywords. RESULTS: A total of 18
      studies from nine countries were found. The results suggest that the prevalence
      of complementary and alternative medicine use among people with diabetes ranges
      from 17% to 72.8%. The most widely used therapies among diabetic populations are
      nutritional supplements, herbal medicines, nutritional advice, spiritual healing
      and relaxation techniques. The characteristics which influence complementary and
      alternative medicine use are age, duration of diabetes, degree of complications
      and self-monitoring of blood glucose. CONCLUSION: Although inconsistency in the
      definition of complementary and alternative medicine and varying research designs
      make estimation of usage prevalence difficult, evidence suggests that a high
      proportion of people with diabetes use these therapies concurrently with
      conventional healthcare services. Healthcare professionals need to be aware of
      this issue and may need to incorporate complementary and alternative medicine
      information into patient assessment and intervention.

PMID- 17442035
TI  - From private to public: negotiating professional and personal identities in
      spiritual care.
AB  - AIM: This paper is an exploration of the challenge of negotiating the highly
      personalized concept of spirituality within the public sphere of professional
      patient interactions. BACKGROUND: Spirituality has become increasingly prominent
      within the nursing discourse, and providing spiritual care is often positioned as
      an ethical obligation of care. However, bringing such a personal concept into the
      public domain of care creates some unique tensions and ethical risks. DISCUSSION:
      Nurses bring three potentially competing identities to spiritual care encounters
      with patients. Firstly, they are professionals with a public trust in health
      promotion and restoration, including those areas that intersect with spiritual
      health. Secondly, they are citizens of a liberal society where non-judgmental
      pluralism as it relates to spirituality is enshrined. Thirdly, they are
      individuals who hold particular beliefs and values about spirituality. Each of
      these identities may result in particular, and potentially conflicting,
      approaches to spiritual care. Ultimately, the identity which nurses choose to
      adopt is often determined by how they view themselves in the spiritual care
      encounter, either as experts with legitimate authority to intervene in the
      spiritual lives of patients or as people in a shared relational encounter. Each
      of these approaches carries ethical risks, although the nature of these risks is
      different. CONCLUSION: The identities which nurses bring to spiritual care
      encounters have far-reaching implications for patient experiences in those
      encounters. Nurses who position themselves as experts run the risk of
      objectifying the spiritual, being experienced as coercive and transcending
      nursings' competence. The work of Martin Buber is presented as a model that,
      while acknowledging competing identities, sets forth a vision of spirituality and
      spiritual care based upon relational reciprocity.

PMID- 17442036
TI  - A nurse- and pharmacist-led treatment advice clinic for patients attending an HIV
      outpatient clinic.
AB  - AIM: This paper is a report of a study to map care pathways, examine the approach
      of different treatment advisors and explore the acceptability of a nurse- and
      pharmacist-led treatment advice clinic in order to aid decision-making for the
      future development and evaluation of the clinic. BACKGROUND: High levels of
      adherence to antiretroviral drugs are a prerequisite for a successful and durable
      virological and immunological response to HIV. Treatment guidelines acknowledge
      that adherence is a process, not a single event, and that adherence support must
      be integrated into clinical follow-up for all patients receiving these drugs.
      METHOD: Data were collected between September 2004 and January 2005 through 17
      consultation observations and 10 patient interviews in a specialist treatment
      advice clinic located within a central London HIV outpatient clinic providing
      care for over 2200 patients, of whom more than 1300 are taking highly active
      antiretroviral therapy. FINDINGS: The nurses and pharmacist had similar
      consultation approaches, although follow-up care varied in extent. Benefits of
      the clinic approach included permitting patients to observe real tablets,
      tailoring regimens to lifestyles and telephone follow-up. These factors,
      particularly telephone support, were perceived by patients to assist with
      adherence. CONCLUSION: The role of telephone support, perceived to assist with
      initial adherence, requires further investigation. Future work is also needed to
      explore the health economics of this approach and to determine the actual impact
      of the clinic on clinical and adherence outcomes.

PMID- 17442037
TI  - The (un)-certainties of district nurses in the context of cultural diversity.
AB  - AIM: This paper is a report of part of a study exploring district nurses'
      understanding and practices in relation to discrimination and inequalities
      issues. BACKGROUND: Clients from minority ethnic groups continue to experience
      inequalities in health status and care provision. District nurses work with a
      wide range of clients, yet research has demonstrated inequities in service
      provision to clients from minority ethnic groups due to organizational,
      professional and personal constraints. METHODS: A qualitative methodology was
      used to explore district nurses' understanding of discrimination and equalities
      issues in the context of their work. Semi-structured interviews were undertaken
      during 2003 with 18 district nurses employed in two primary care organizations in
      England providing healthcare services to a large and culturally diverse
      population. FINDINGS: District nurses' accounts were marked by uncertainty,
      suggesting that many lacked confidence when discussing issues of ethnicity and
      cultural difference. There were marked differences in the extent to which they
      appeared to recognize or engage with clients' experiences of discrimination or
      inequalities, or to recognize inequitable service provision to clients from
      minority ethnic groups. Key issues were a lack of provision of district nursing
      services to some clients, and failures to meet clients' language and
      communication needs, and although reflecting organizational constraints, such
      continuing inequities were largely unquestioned. CONCLUSION: There is a need for
      further educational and practice developments to enable district nurses to
      provide more equitable care to clients from culturally diverse communities,
      ensuring that the key professional discourse of individual care and advocacy are
      fully realized in their work with all clients.

PMID- 17442038
TI  - Translation of scales in cross-cultural research: issues and techniques.
AB  - AIMS: This paper is a report of a study designed to: (i) describe issues and
      techniques of translation of standard measures for use in international research;
      (ii) identify a user-friendly and valid translation method when researchers have
      limited resources during translation procedure; and (iii) discuss translation
      issues using data from a pilot study as an example. BACKGROUND: The process of
      translation is an important part of cross-cultural studies. Cross-cultural
      researchers are often confronted by the need to translate scales from one
      language to another and to do this with limited resources. METHOD: The lessons
      learned from our experience in a pilot study are presented to underline the
      importance of using appropriate translation procedures. The issues of the back
      translation method are discussed to identify strategies to ensure success when
      translating measures. FINDINGS: A combined technique is an appropriate method to
      maintain the content equivalences between the original and translated instruments
      in international research. There are several possible combinations of translation
      techniques. However, there is no gold standard of translation techniques because
      the research environment (e.g. accessibility and availability of bilingual
      people) and the research questions are different. CONCLUSIONS: It is important to
      use appropriate translation procedures and to employ a combined translation
      technique based on the research environment and questions.

PMID- 17442039
TI  - Nurses' discourse in contraceptive prescribing: an analysis using Foucault's
      'procedures of exclusion'.
AB  - AIM: This paper is a report of an analysis of the discourse about contraceptive
      efficacy and side effects used by nurses when prescribing contraception.
      BACKGROUND: All women seeking contraception should be informed of the efficacy
      and potential adverse effects of the particular method they are considering. This
      information facilitates an informed choice. Women also require this information
      in order to monitor for any side effects. Paradoxically, side effects are also a
      key factor in reducing adherence with contraceptive regimens. However, there is
      no literature that explores specifically how this issue is addressed in clinical
      consultations, or places these practices in a theoretical context. METHOD: Forty
      nine consultations between nurses and women in sexual health clinics were audio
      recorded during 2002. Data were subject to a discourse analysis using Foucault's
      'procedures of exclusion' to explore the discursive construction of contraceptive
      efficacy and side effects FINDINGS: The nurses employed specific discursive
      strategies when discussing contraception. When addressing efficacy, discourse
      centred on medico-statistical facts, but side effects were described in lay terms
      that minimized their severity. Nurses contextualized contraceptive side effects
      within potential problems that women might experience in pregnancy, and also
      attempted to 'normalize' contraceptive-related problems. CONCLUSION: Discourse
      and its deployment play a key role in practitioner-client relationships that
      sexual health nurses need to become more aware of how they discuss clinical
      issues about contraception with women. Clinical data on contraceptive side
      effects are present in the literature, and it is important that sexual health
      nurses use this to help women make truly informed decisions.

PMID- 17442040
TI  - Pressure ulcer care in Spain: nurses' knowledge and clinical practice.
AB  - AIM: This paper is a report of a study to determine: (a) Spanish nurses' level of
      knowledge of existing guidelines for pressure ulcer prevention and treatment, (b)
      the level of implementation of this knowledge in clinical practice and (c) the
      professional and educational factors that influence knowledge and practice.
      BACKGROUND: Improvement in pressure ulcer care depends both on the dissemination
      of knowledge and on its implementation in clinical practice. Studies carried out
      in several countries have demonstrated gaps in knowledge about recommendations
      for pressure ulcer care and deficiencies in their implementation. METHODS: A
      survey was carried out between September 2001 and June 2002, targeting a cluster
      randomized sample of 2006 Registered Nurses and Licensed Practice Nurses working
      at hospitals, primary healthcare centres and elder care centres in Andalusia
      (Spain). RESULTS: The response rate was 36.9% (n = 740). The level of knowledge
      of prevention interventions was 79.1%, while that of treatment interventions was
      75.9%. The levels of implementation in clinical practice were notably lower:
      68.1% for prevention, and 65.3% for treatment. Nurses holding a university degree
      obtained higher scores, and those who had received specific education in pressure
      ulcer care obtained higher scores both for knowledge and clinical practice.
      Taking part in research projects also improved knowledge implementation.
      CONCLUSION: Although most of the recommendations on pressure ulcer care found in
      guidelines are well known by nurses, there is a group of interventions about
      which they have insufficient knowledge and low implementation rates.

PMID- 17442041
TI  - Capsaicin-induced apoptosis of glioma cells is mediated by TRPV1 vanilloid
      receptor and requires p38 MAPK activation.
AB  - We provide evidence on the expression of the transient receptor potential
      vanilloid type-1 (TRPV1) by glioma cells, and its involvement in capsaicin (CPS)
      induced apoptosis. TRPV1 mRNA was identified by quantitative RT-PCR in U373, U87,
      FC1 and FLS glioma cells, with U373 cells showing higher, and U87, FC1 and FLS
      cells lower TRPV1 expression as compared with normal human astrocytes. By flow
      cytometry we found that a substantial portion of both normal human astrocytes,
      and U87 and U373 glioma cells express TRPV1 protein. Moreover, we analyzed the
      expression of TRPV1 at mRNA and protein levels of glioma tissues with different
      grades. We found that TRPV1 gene and protein expression inversely correlated with
      glioma grading, with marked loss of TRPV1 expression in the majority of grade IV
      glioblastoma multiforme. We also described that CPS trigger apoptosis of U373,
      but not U87 cells. CPS-induced apoptosis involved Ca(2+) influx, p38 but not
      extracellular signal-regulated mitogen-activated protein kinase activation,
      phosphatidylserine exposure, mitochondrial permeability transmembrane pore
      opening and mitochondrial transmembrane potential dissipation, caspase 3
      activation and oligonucleosomal DNA fragmentation. TRPV1 was functionally
      implicated in these events as they were markedly inhibited by the TRPV1
      antagonist, capsazepine. Finally, p38 but not extracellular signal-regulated
      protein kinase activation was required for TRPV1-mediated CPS-induced apoptosis
      of glioma cells.

PMID- 17442043
TI  - Induction of interleukin-1beta by interleukin-4 in lipopolysaccharide-treated
      mixed glial cultures: microglial-dependent effects.
AB  - Glial-secreted proinflammatory mediators are dynamically involved in central
      nervous system responses to exogenous stimuli such as infection, neurotoxins, and
      nerve injury. The therapeutic use of anti-inflammatory agents may reduce certain
      central nervous system pathology induced by inflammatory responses. We
      investigated the role of interleukin (IL)-4 in modulating the production of
      proinflammatory mediators from lipopolysaccharide-stimulated mixed glia in vitro.
      Interestingly, IL-4 significantly enhanced IL-1beta secretion and did not affect
      monocyte chemoattractant protein-1 release, even though IL-4 considerably
      inhibited IL-6, tumor necrosis factor alpha, and nitric oxide production from rat
      neonatal mixed glia. Further, IL-4 exhibited inhibitory effects on IL-1beta
      production in microglial-enriched cultures, while significantly increasing IL
      1beta production in microglial-depleted glia. The enhancing effect of IL-4 on IL
      1beta production was found to be inversely correlated with the percentage of
      microglia present in the mixed glial population. In summary, IL-4 did not act as
      a global anti-inflammatory cytokine and in fact, under certain situations
      enhanced IL-1beta secretion. We conclude that IL-4 exerts its anti-inflammatory
      effects in a limited and target-specific manner, which is delicately regulated by
      the cellular microenvironment. Therefore, precaution should be taken when
      clinically using IL-4 to treat diseases manifested by overt inflammatory
      responses.

PMID- 17442042
TI  - A glycogen phosphorylase inhibitor selectively enhances local rates of glucose
      utilization in brain during sensory stimulation of conscious rats: implications
      for glycogen turnover.
AB  - Glycogen is degraded during brain activation but its role and contribution to
      functional energetics in normal activated brain have not been established. In the
      present study, glycogen utilization in brain of normal conscious rats during
      sensory stimulation was assessed by three approaches, change in concentration,
      release of (14)C from pre-labeled glycogen and compensatory increase in
      utilization of blood glucose (CMR(glc)) evoked by treatment with a glycogen
      phosphorylase inhibitor. Glycogen level fell in cortex, (14)C release increased
      in three structures and inhibitor treatment caused regionally selective
      compensatory increases in CMR(glc) over and above the activation-induced rise in
      vehicle-treated rats. The compensatory rise in CMR(glc) was highest in sensory
      parietal cortex where it corresponded to about half of the stimulus-induced rise
      in CMR(glcf) in vehicle-treated rats; this response did not correlate with
      metabolic rate, stimulus-induced rise in CMR(glc) or sequential station in
      sensory pathway. Thus, glycogen is an active fuel for specific structures in
      normal activated brain, not simply an emergency fuel depot and flux-generated
      pyruvate greatly exceeded net accumulation of lactate or net consumption of
      glycogen during activation. The metabolic fate of glycogen is unknown, but adding
      glycogen to the fuel consumed during activation would contribute to a fall in
      CMR(O2)/CMR(glc) ratio.

PMID- 17442044
TI  - EAAT4 phosphorylation at the SGK1 consensus site is required for transport
      modulation by the kinase.
AB  - EAAT4 (SLC1A6) is a Purkinje-Cell-specific post-synaptic excitatory amino acid
      transporter that plays a major role in clearing synaptic glutamate. EAAT4
      abundance and function is known to be modulated by the serum and glucocorticoid
      inducible kinase (SGK) 1 but the precise mechanism of kinase action has not been
      defined yet. The present work aims to identify the molecular mechanism of EAAT4
      modulation by the kinase. The EAAT4 sequence bears two putative SGK1 consensus
      sites (at Thr40 and Thr504) at the amino and carboxy terminus that are conserved
      among species. Expression studies in Xenopus oocytes demonstrated that EAAT4
      mediated [(3)H] glutamate uptake and cell surface abundance are enhanced by co
      expression of SGK1. Disruption of the SGK1 phosphorylation site at threonine 40
      ((T40A)EAAT4) or of both phosphorylation sites ((T40AT504A)EAAT4) abrogated the
      effect of SGK1 on transporter function and expression. SGK1 modulates several
      transport proteins via inhibition of the ubiquitin ligase Nedd4-2. Co-expression
      of Nedd4-2 inhibited wild-type EAAT4 but not the (T40AT504A)EAAT4 mutant.
      Besides, RNA interference-mediated reduction of endogenous Nedd4-2 (xNedd4-2)
      expression increased the activity of the transporter. In conclusion, maximal
      glutamate transport modulation by SGK1 is accomplished by direct EAAT4
      stimulation and to a lesser extent by inhibition of intrinsic Nedd4-2.

PMID- 17442045
TI  - An oligodendrocyte enhancer in a phylogenetically conserved intron region of the
      mammalian myelin gene Opalin.
AB  - Opalin is a transmembrane protein detected specifically in mammalian
      oligodendrocytes. Opalin homologs are found only in mammals and not in the genome
      sequences of other animal classes. We first determined the nucleotide sequences
      of Opalin orthologs and their flanking regions derived from four prosimians, a
      group of primitive primates. A global comparison revealed that an evolutionarily
      conserved region exists in the first intron of Opalin. When the conserved domain
      was assayed for its enhancer activity in transgenic mice, oligodendrocyte
      directed expression was observed. In an oligodendroglial cell line, Oli-neu, the
      conserved domain showed oligodendrocyte-directed expression. The conserved domain
      is composed of eight subdomains, some of which contain binding sites for Myt1 and
      cAMP-response element binding protein (CREB). Deletion analysis and
      cotransfection experiments revealed that the subdomains have critical roles in
      Opalin gene expression. Over-expression of Myt1, treatment of the cell with
      leukemia inhibitory factor (LIF), and cAMP analog (CREB activator) enhanced the
      expression of endogenous Opalin in Oli-neu cells and activated the
      oligodendrocyte enhancer. These results suggest that LIF, cAMP signaling cascades
      and Myt1 play significant roles in the differentiation of oligodendrocytes
      through their action on the Opalin oligodendrocyte enhancer.

PMID- 17442046
TI  - Lysophosphatidic acid rescues RhoA activation and phosphoinositides levels in
      astrocytes exposed to ethanol.
AB  - Long-term ethanol treatment substantially impairs glycosylation and membrane
      trafficking in primary cultures of rat astrocytes. Our previous studies indicated
      that these effects were attributable to a primary alteration in the dynamics and
      organization of the actin cytoskeleton, although the molecular mechanism(s)
      remains to be elucidated. As small Rho GTPases and phosphoinositides are involved
      in the actin cytoskeleton organization, we now explore the effects of chronic
      ethanol treatment on these pathways. We show that chronic ethanol treatment of
      rat astrocytes specifically reduced endogenous levels of active RhoA as a result
      of the increase of in the RhoGAP activity. Furthermore, ethanol-treated
      astrocytes showed reduced phosphoinositides levels. When lysophosphatidic acid
      was added to ethanol-treated astrocytes, it rapidly reverted actin cytoskeleton
      reorganization and raised active RhoA levels and phosphoinositides content to
      those observed in untreated astrocytes. Overall, our results indicate that the
      harmful effects of chronic exposure to ethanol on a variety of actin dynamics
      associated cellular events are primarily because of alterations of activated RhoA
      and phosphoinositides pools.

PMID- 17442047
TI  - Modulation of hippocampal calcium signalling and plasticity by serine/threonine
      protein phosphatases.
AB  - Kinases and phosphatases act antagonistically to maintain physiological
      phosphorylation/dephosphorylation at numerous intracellular sites critical for
      neuronal signalling. In this study, it was found that inhibition of
      serine/threonine phosphatases by exposure of hippocampal slices to okadaic acid
      (OA) or cantharidin (CA; 100 nmol/L) for 2 h resulted in reduced basal synaptic
      transmission and blocked the induction of synaptic plasticity in the form of long
      term potentiation as determined by electrophysiological analysis. Fura-2 Ca(2+)
      imaging revealed a bidirectional modulation of N-methyl-D-aspartate (NMDA) 
      mediated Ca(2+) responses and reduced KCl-mediated Ca(2+) responses in neonatal
      cultured hippocampal neurons after phosphatase inhibition. While OA inhibited
      NMDA-induced Ca(2+) influx both acutely and after incubation, CA-enhanced
      receptor-mediated Ca(2+) signalling at low concentrations (1 nmol/L) but reduced
      NMDA and KCl-mediated Ca(2+) responses at higher concentrations (100 nmol/L).
      Changes in Ca(2+) signalling were accompanied by increased phosphorylation of
      cytoskeletal proteins tau and neurofilament and the NMDA receptor subunit NR1 in
      selective treatments. Incubation with OA (100 nmol/L) also led to the disruption
      of the microtubule network. This study highlights novel signalling effects of
      prolonged inhibition of protein phosphatases and suggests reduced post-synaptic
      signalling as a major mechanism for basal synaptic transmission and long-term
      potentiation impairments.

PMID- 17442048
TI  - Mechanisms of axon guidance: membrane dynamics and axonal transport in semaphorin
      signalling.
AB  - The intricate geometry of neuronal networks poses many unique cell-biological
      problems regarding the way a growing axon responds to its environment. Several
      groups of ligand-receptor pairs have been identified to regulate such processes.
      In this study, we take class 3 semaphorins as an example and review what is known
      about the intracellular movements of semaphorins throughout neuronal cells,
      transport support structures and location of release sites. We discuss how their
      receptor trafficking may contribute to regulate membrane dynamics underlying
      growth cone motility and the physiological contribution made by class 3
      semaphorins-induced acceleration of axoplasmic transport on neurite development.

PMID- 17442049
TI  - The lack of CB1 receptors prevents neuroadapatations of both NMDA and GABA(A)
      receptors after chronic ethanol exposure.
AB  - As the contribution of cannabinoid (CB1) receptors in the neuroadaptations
      following chronic alcohol exposure is unknown, we investigated the
      neuroadaptations induced by chronic alcohol exposure on both NMDA and GABA(A)
      receptors in CB1-/- mice. Our results show that basal levels of hippocampal
      [(3)H]MK-801 ((1)-5-methyl-10,11-dihydro-5Hdibenzo[a,d]cyclohepten-5,10-imine)
      binding sites were decreased in CB1-/- mice and that these mice were also less
      sensitive to the locomotor effects of MK-801. Basal level of both hippocampal and
      cerebellar [(3)H]muscimol binding was lower and sensitivity to the hypothermic
      effects of diazepam and pentobarbital was increased in CB1-/- mice.
      GABA(A)alpha1, beta2, and gamma2 and NMDA receptor (NR) 1 and 2B subunit mRNA
      levels were altered in striatum of CB1-/- mice. Our results also showed that
      [(3)H]MK-801 binding sites were increased in cerebral cortex and hippocampus
      after chronic ethanol ingestion only in wild-type mice. Chronic ethanol ingestion
      did not modify the sensitivity to the locomotor effects of MK-801 in both
      genotypes. Similarly, chronic ethanol ingestion reduced the number of
      [(3)H]muscimol binding sites in cerebral cortex, but not in cerebellum, only in
      CB1+/+ mice. We conclude that lifelong deletion of CB1 receptors impairs
      neuroadaptations of both NMDA and GABA(A) receptors after chronic ethanol
      exposure and that the endocannabinoid/CB1 receptor system is involved in alcohol
      dependence.

PMID- 17442050
TI  - Characterization of mature rat oligodendrocytes: a proteomic approach.
AB  - Oligodendrocytes are glial cells responsible for the synthesis and maintenance of
      myelin in the central nervous system (CNS). Oligodendrocytes are vulnerable to
      damage occurring in a variety of neurological diseases. Understanding
      oligodendrocyte biology is crucial for the dissemination of de- and remyelination
      mechanisms. The goal of the present study is the construction of a protein
      database of mature rat oligodendrocytes. Post-mitotic oligodendrocytes were
      isolated from mature Wistar rats and subjected to immunocytochemistry. Proteins
      were extracted and analyzed by means of two-dimensional gel electrophoresis and
      two-dimensional liquid chromatography, both coupled to mass spectrometry. The
      combination of the gel-based and gel-free approach resulted in confident
      identification of a total of 200 proteins. A minority of proteins were identified
      in both proteomic strategies. The identified proteins represent a variety of
      functional groups, including novel oligodendrocyte proteins. The results of this
      study emphasize the power of the applied proteomic strategy to study known or to
      reveal new proteins and to investigate their regulation in oligodendrocytes in
      different disease models.

PMID- 17442051
TI  - A Critical role for Bim in retinal ganglion cell death.
AB  - Optic nerve transection results in the death of retinal ganglion cells (RGCs) by
      apoptosis. Apoptosis is regulated by the Bcl-2 family of proteins, of which the
      Bcl-2 homology (BH3) -only proteins forms a subset. As BH3-only proteins have
      been shown to play a significant role in regulating cell death in the central
      nervous system, we wished to investigate the role of Bcl-2 interacting mediator
      of cell death (Bim), a prominent member of this protein family in the regulation
      of cell death in the RGC layer using in vitro retinal explants. In this study, we
      use an innovative retinal shaving procedure to isolate the cells of the ganglion
      cell layer to use for western blotting. Members of the BH3-only protein family
      are down-regulated during retinal development and are not normally expressed in
      the adult retina. Using this procedure, we demonstrate that Bim is re-expressed
      and its expression is increased over time following axotomy. Expression of Bad
      and Bik decreases over the same time course, whereas there is no indication that
      Bid and Puma are re-expressed. We show that explants from Bim knockout mice are
      resistant to axotomy-induced death when compared with their wild-type
      counterparts. Genetic deletion of Bim also prevents caspase 3 cleavage. The
      activity of Bim can be negatively regulated by phosphorylation. We show that the
      decrease of Bim phosphorylation correlates with a decrease in expression of
      survival kinases such as pAkt and pERK over the same time course. These results
      implicate Bim re-expression as being essential for axotomy-induced death of RGCs
      and that phosphorylation of Bim negatively regulates its activity in RGCs.

PMID- 17442052
TI  - Activation of recombinant human TRPV1 receptors expressed in SH-SY5Y human
      neuroblastoma cells increases [Ca(2+)](i), initiates neurotransmitter release and
      promotes delayed cell death.
AB  - The transient receptor potential (TRP) vanilloid receptor subtype 1 (TRPV1) is a
      ligand-gated, Ca(2+)-permeable ion channel in the TRP superfamily of channels. We
      report the establishment of the first neuronal model expressing recombinant human
      TRPV1 (SH-SY5Y(hTRPV1)). SH-SY5Y human neuroblastoma cells were stably
      transfected with hTRPV1 using the Amaxa Biosystem (hTRPV1 in pIREShyg2 with
      hygromycin selection). Capsaicin, olvanil, resiniferatoxin and the
      endocannabinoid anandamide increased [Ca(2+)](i) with potency (EC(50)) values of
      2.9 nmol/L, 34.7 nmol/L, 0.9 nmol/L and 4.6 micromol/L, respectively. The
      putative endovanilloid N-arachidonoyl-dopamine increased [Ca(2+)](i) but this
      response did not reach a maximum. Capsaicin, anandamide, resiniferatoxin and
      olvanil mediated increases in [Ca(2+)](i) were inhibited by the TRPV1 antagonists
      capsazepine and iodo-resiniferatoxin with potencies (K(B)) of approximately 70
      nmol/L and 2 nmol/L, respectively. Capsaicin stimulated the release of pre
      labelled [(3)H]noradrenaline from monolayers of SH-SY5Y(hTRPV1) cells with an
      EC(50) of 0.6 nmol/L indicating amplification between [Ca(2+)](i) and release. In
      a perfusion system, we simultaneously measured [(3)H]noradrenaline release and
      [Ca(2+)](i) and observed that increased [Ca(2+)](i) preceded transmitter release.
      Capsaicin treatment also produced a cytotoxic response (EC(50) 155 nmol/L) that
      was antagonist-sensitive and mirrored the [Ca(2+)](I) response. This model
      displays pharmacology consistent with TRPV1 heterologously expressed in standard
      non-neuronal cells and native neuronal cultures. The advantage of SH-SY5Y(hTRPV1)
      is the ability of hTRPV1 to couple to neuronal biochemical machinery and produce
      large quantities of cells.

PMID- 17442053
TI  - Genomic and proteomic microglial profiling: pathways for neuroprotective
      inflammatory responses following nerve fragment clearance and activation.
AB  - Microglia, a primary immune effector cell of the central nervous system (CNS)
      affects homeostatic, neuroprotective, regenerative and degenerative outcomes in
      health and disease. Despite these broad neuroimmune activities linked to specific
      environmental cues, a precise cellular genetic profile for microglia in the
      context of disease and repair has not been elucidated. To this end we used
      nucleic acid microarrays, proteomics, immunochemical and histochemical tests to
      profile microglia in neuroprotective immune responses. Optic and sciatic nerve
      (ON and SN) fragments were used to stimulate microglia in order to reflect immune
      consequences of nervous system injury. Lipopolysaccharide and latex beads-induced
      microglial activation served as positive controls. Cytosolic and secreted
      proteins were profiled by surface enhanced laser desorption ionization-time of
      flight (SELDI-TOF) ProteinChip, 1D and 2D difference gel electrophoresis.
      Proteins were identified by peptide sequencing with tandem mass spectrometry,
      ELISA and western blot tests. Temporal expression of pro-inflammatory cytokines,
      antioxidants, neurotrophins, and lysosomal enzyme expression provided, for the
      first time, a unique profile of secreted microglia proteins with neuroregulatory
      functions. Most importantly, this molecular and biochemical signature supports a
      broad range of microglial functions for debris clearance and promotion of neural
      repair after injury.

PMID- 17442054
TI  - Atorvastatin partially prevents an inflammatory barrier breakdown of cultured
      human brain endothelial cells at a pharmacologically relevant concentration.
AB  - 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (i.e. statins) are
      currently under clinical investigation as a prophylactic immunomodulatory
      treatment for neurological diseases where an inflammatory disruption of the blood
      brain barrier plays a pathogenic role. Here, we investigated whether atorvastatin
      pre-treatment modulates inflammatory-induced barrier dysfunction of cultured
      human brain microvascular endothelial cells (HBMEC). Pre-treatment of
      immortalized HBMEC with atorvastatin (50 nmol/L to 1 micromol/L) dose-dependently
      prevented an inflammatory up-regulation of monocyte chemoattractant protein
      1/CCL2 but not of interleukin-8/CXCL8 and intercellular adhesion molecule-1
      expression by tumor necrosis factor-alpha or interleukin-1beta. It antagonized an
      inflammatory up-regulation of claudin-3 expression while zonula occludens-1 and
      occludin protein levels remained unaltered. Like immortalized HBMEC, primary
      HBMEC also showed a reduction of claudin-3 and of inducible CCL2 expression
      following atorvastatin pre-treatment. On a functional level, atorvastatin pre
      treatment of HBMEC strongly and dose-dependently reduced adhesion of activated T
      lymphocytes to pre-activated primary endothelium. Atorvastatin effects could
      partially be abolished by parallel mevalonate treatment. These anti-inflammatory
      effects of atorvastatin were observed already at a pharmacologically relevant
      concentration of 50 nmol/L. Our results obtained with human brain endothelial
      cells demonstrate how statins may partially prevent an inflammatory-mediated
      blood-brain barrier breakdown in humans.

PMID- 17442055
TI  - Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in
      the mammalian brain.
AB  - The tryptophan metabolite kynurenic acid (KYNA), which is produced enzymatically
      by the irreversible transamination of l-kynurenine, is an antagonist of alpha7
      nicotinic and NMDA receptors and may thus modulate cholinergic and glutamatergic
      neurotransmission. Two kynurenine aminotransferases (KAT I and II) are currently
      considered the major biosynthetic enzymes of KYNA in the brain. In this study, we
      report the existence of a third enzyme displaying KAT activity in the mammalian
      brain. The novel KAT had a pH optimum of 8.0 and a low capacity to transaminate
      glutamine or alpha-aminoadipate (the classic substrates of KAT I and KAT II,
      respectively). The enzyme was inhibited by aspartate, glutamate, and quisqualate
      but was insensitive to blockade by glutamine or anti-KAT II antibodies. After
      purification to homogeneity, the protein was sequenced and the enzyme was
      identified as mitochondrial aspartate aminotransferase (mitAAT). Finally, the
      relative contributions of KAT I, KAT II, and mitAAT to total KAT activity were
      determined in mouse, rat, and human brain at physiological pH using anti-mitAAT
      antibodies. KAT II was most abundant in rat and human brain, while mitAAT played
      the major role in mouse brain. It remains to be seen if mitAAT participates in
      cerebral KYNA synthesis under physiological and/or pathological conditions in
      vivo.

PMID- 17442056
TI  - Neurochemical, morphological, and neurophysiological abnormalities in retinas of
      Sandhoff and GM1 gangliosidosis mice.
AB  - Retinal abnormalities are well documented in patients with ganglioside storage
      diseases. The total content and distribution of retinal glycosphingolipids was
      studied for the first time in control mice and in Sandhoff disease (SD) and GM1
      gangliosidosis mice. Light and electron microscopy of the SD and the GM1 retinas
      revealed storage in ganglion cells. Similar to previous findings in rat retina,
      GD3 was the major ganglioside in mouse retina, while GM2 and GM1 were minor
      species. Total ganglioside content was 44% and 40% higher in the SD and the GM1
      retinas, respectively, than in the control retinas. Furthermore, GM2 and GM1
      content were 11-fold and 51-fold higher in the SD and the GM1 retinas than in the
      control retinas, respectively. High concentrations of asialo-GM2 and asialo-GM1
      were found in the SD and the GM1 retinas, respectively, but were undetectable in
      the control retinas. The GSL abnormalities in the SD and the GM1 retinas reflect
      significant reductions in beta-hexosaminidase and beta-galactosidase enzyme
      activities, respectively. Although electroretinograms appeared normal in the SD
      and the GM1 mice, visual evoked potentials were subnormal in both mutants,
      indicating visual impairments. Our findings present a model system for assessing
      retinal pathobiology and therapies for the gangliosidoses.

PMID- 17442057
TI  - NBS1, the Nijmegen breakage syndrome gene product, regulates neuronal
      proliferation and differentiation.
AB  - Nijmegen breakage syndrome (NBS) is an autosomal recessive disorder,
      characterized by progressive microcephaly, growth retardation, immunodeficiency,
      and pre-disposition to tumor formation. To investigate the functions of the NBS
      gene product, NBS1, on neurons, PC12 cells overexpressing NBS1 and related
      mutants and primary cortical neuronal culture were used in the present study.
      Small interfering RNA (siRNA) was applied to repress the expression of endogenous
      Nbs1 in PC12 cells and primary cortical neurons. We demonstrated that
      overexpression of NBS1 increases cellular proliferation and decreases the
      apoptosis of PC12 cells in serum withdrawal and ionizing irradiation, through the
      activation of phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway.
      Overexpression of NBS1 also decreases neurite elongation on PC12 cells under
      nerve growth factor stimulation. Transfection of NBS1-overexpressing PC12 cells
      with a dominant negative Akt mutant attenuates the neuroprotection and cellular
      proliferation effects of NBS1 while having no effect on neurite elongation. PC12
      cells overexpressing NBS657del5 and NBS653 mutants, in which the major NBS1
      protein in cells are truncated proteins, have decreased cellular proliferation,
      increased cell death, and decreased neurite elongation compared with those of
      control PC12 cells. Repression of Nbs1 by siRNA decreases the PI 3-kinase
      activity and Akt phosphorylation levels, and induces neurite elongation in PC12
      cells even without nerve growth factor stimulation. Repression of Nbs1 by siRNA
      in primary cortical neurons also increased neurite elongation, but increased
      neuronal death. We conclude that NBS1 can regulate neuronal proliferation and
      neuroprotection via PI 3-kinase/Akt pathway while regulating neuronal
      differentiation in a different pathway. Excessive accumulation of truncated
      protein secondary to 657del5 mutation may be detrimental to neurons, leading to
      defective neuronal proliferation and differentiation.

PMID- 17442058
TI  - Cerebral metastasis of peripheral primitive neuroectodermal tumour (pPNET) - use
      of cytogenetic abnormalities in diagnosis.

PMID- 17442059
TI  - Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3
      and ultrastructural alterations in different disease stages.
AB  - Cerebral malaria (CM) is associated with high mortality and morbidity as a
      certain percentage of survivors suffers from persistent neurological sequelae.
      The mechanisms leading to death and functional impairments are yet not fully
      understood. This study investigated biochemical and morphological markers of
      apoptosis in the brains of mice infected with Plasmodium berghei ANKA. Cleaved
      caspase-3 was detected in the brains of animals with clinical signs of CM and
      immunoreactivity directly correlated with the clinical severity of the disease.
      Caudal parts of the brain showed more intense immunoreactivity for cleaved
      caspase-3. Double-labelling experiments revealed processing of caspase-3
      primarily in neurons and oligodendrocytes. These cells also exhibited apoptotic
      like morphological profiles in ultrastructural analysis. Further, cleavage of
      caspase-3 was found in endothelial cells. In contrast to neurons and
      oligodendrocytes, apoptosis of endothelial cells already occurred in early stages
      of the disease. Our results are the first to demonstrate processing of caspase-3
      in different central nervous system cells of animals with CM. Apoptosis of
      endothelial cells may represent a critical issue for the development of the
      disease in the mouse model. Neurological signs and symptoms might be
      attributable, at least in part, to apoptotic degeneration of neurons and glia in
      advanced stages of murine CM.

PMID- 17442060
TI  - Effect of ammonia on ciliary neurotrophic factor mRNA and protein expression and
      its upstream signalling pathway in cultured rat astroglial cells: possible
      implication of c-fos, Sp1 and p38MAPK.
AB  - Ciliary neurotrophic factor (CNTF) may be implicated in the pathogenetic
      mechanisms of hepatic encephalopathy. We tested this hypothesis by treating
      confluent primary cultures of rat astroglial cells with ammonium chloride for
      various periods and analysing the effect of ammonia on the signalling pathway
      that regulates CNTF mRNA and protein expression. Ammonia treatment induced a dose
      and time-dependent reduction in CNTF mRNA and protein expression. Surface
      enhanced laser desorption/ionization-time-of-flight mass spectrometry analysis of
      CNTF in the culture medium demonstrated that ammonia also induced a significant
      decrease in CNTF release. In addition, ammonia affected Sp1 and c-fos,
      transcription factors that regulate CNTF mRNA and protein expression, which
      showed partial dephosphorylation and significantly lower mRNA and protein levels.
      Total content of p38MAPK (for which Sp1 and c-fos are substrates) was unaffected
      by ammonia, although the diphosphorylated (active) form was significantly reduced
      after ammonia exposure.

PMID- 17442061
TI  - Relevance of combinatorial profiles of intermediate filaments and transcription
      factors for glioma histogenesis.
AB  - In order to define specific markers for histogenesis of three well-characterized
      subgroups of human gliomas (pilocytic astrocytomas, glioblastoma multiforme and
      oligodendrogliomas), we studied the expression of relevant markers that
      characterize gliomagenesis, by immunohistochemistry and in situ hybridization.
      They include the intermediate filament proteins glial fibrillary acidic protein
      (GFAP), vimentin and nestin, the transcription factors Olig2, Nkx2.2 and Sox10,
      and the proteolipid protein transcripts plp/dm20. We show that the three major
      categories of human gliomas express a combinatorial profile of markers that gives
      new insights to their histogenesis and may help diagnosis. Pilocytic astrocytomas
      strongly express GFAP, vimentin, Olig2, Nkx2.2 and Sox10 but not nestin. In
      contrast, glioblastomas strongly express GFAP, vimentin and nestin but these
      tumours are heterogeneous regarding the expression of the transcription factors
      studied. Finally, in oligodendrogliomas, intermediate filament proteins are
      generally not observed whereas Olig2 was found in almost all tumour cells nuclei
      while only a subpopulation of tumour cells expressed Nkx2.2 and Sox10.

PMID- 17442062
TI  - White matter lesions in an unselected cohort of the elderly: astrocytic,
      microglial and oligodendrocyte precursor cell responses.
AB  - White matter lesions in an unselected cohort of the elderly: astrocytic,
      microglial and oligodendrocyte precursor cell responsesHyperintense lesions are
      frequently identified in T2-weighted magnetic resonance images (MRI) in the
      ageing brain. The pathological correlate and pathogenesis of white matter lesions
      (WML) remain unclear, and it is uncertain whether pathology and pathogenesis
      differ in periventricular lesions (PVL) compared with deep subcortical lesions
      (DSCL). Therefore we characterized astrocytic, microglial and oligodendrocyte
      responses in PVL and DSCL and compared them with control white matter using
      immunohistochemistry. Both PVL and DSCL were associated with severe myelin loss
      and increased microglia (P = 0.069 and P < 0.001), compared with nonlesional aged
      brain. Clasmatodendritic astroglia, immunoreactive for the serum protein
      fibrinogen, were present in 67% of PVL examined and 42% of DSCL. Compared with
      control and DSCL cases, more MAP-2 +13 positive remyelinating oligodendrocytes (P
      = 0.003 and P = 0.035) and platelet-derived growth factor alpha receptor positive
      reactive astrocytes (P < 0.001) were present in the perilesional white matter of
      PVL. In addition to a role for hypoperfusion, our data suggest that dysfunction
      of the blood-brain barrier may also contribute to the pathogenesis of a
      proportion of cerebral WML associated with ageing, and that attempts at
      remyelination are only associated with PVL and not DSCL.

PMID- 17442063
TI  - Stereological analysis of neuropil threads in the hippocampal formation:
      relationships with Alzheimer's disease neuronal pathology and cognition.
AB  - Although neuropil threads are thought to account for 85-90% of cortical tau
      pathology in brain ageing, their clinical significance remains controversial.
      Previous studies have measured densities, rather than absolute numbers, and most
      did not take into account possible interactions among the pathological hallmarks
      of Alzheimer's disease (AD). We report here stereological estimates of total
      neurofibrillary tangle (NFT) and neuron numbers as well as total amyloid volume
      and neuropil thread (NT) length, in the hippocampus and entorhinal cortex of 19
      very old individuals (age range: 83-101 years) with various degrees of cognitive
      decline. Total NT length in all areas studied increased in mildly demented cases
      but showed a marked decrease in Clinical Dementia Rating (CDR) scale 3 cases.
      Both total NFT and neuron numbers were related to NT length in the CA1 field and
      entorhinal cortex. A strong positive relationship was also present between the
      total NFT numbers in the entorhinal cortex and NT length in the CA1 field and
      dentate gyrus. Total NT length in the CA1 field was related to both CDR scores
      and presence or absence of dementia explaining 7% and 37% of their variability
      respectively. In multivariate models, this relationship was highly dependent on
      the severity of NFT formation in this area. Our data reveal that NT formation in
      hippocampal subdivisions and entorhinal cortex accompanies AD neuronal pathology
      in early stages of the degenerative process, yet its rate may decrease in severe
      dementia. In terms of clinicopathological correlations, NT length in the
      hippocampal formation does not represent an independent marker of dementia
      severity.

PMID- 17442064
TI  - Nuclear factor kappa-B p50 and p65 subunits expression in dementia with Lewy
      bodies.
AB  - Dementia with Lewy bodies (DLB) is the second most common cause of
      neurodegenerative dementia after Alzheimer's disease (AD). Parkinsonism in DLB is
      mainly caused by neuronal loss with Lewy bodies (LBs) in the substantia nigra,
      thereby inducing degeneration of the nigrostriatal dopaminergic pathway similar
      to that in Parkinson's disease (PD). To clarify the pathogenesis of DLB, it is
      important to investigate the mechanisms involved in the degenerative process of
      LB-bearing neurones. Several reports suggest a role for nuclear factor kappa-B
      (NFkappaB) in the manifestation of neurodegenerative conditions such as AD and
      PD. The aim of the present study was to investigate whether NFkappaB subunits are
      involved in the pathogenesis of neurodegeneration in DLB by measuring tyrosine
      hydroxylase (TH), NFkappaB p65 and p50 protein expression in frontal cortex and
      substantia nigra pars compacta of DLB and control human brains. An increase,
      although not statistically significant, in nigral TH expression in DLB cases was
      observed. There were no differences in the cortical and nigral expression levels
      of NFkappaB p65 subunit between control and DLB cases. Western blots of the
      frontal cortex showed no differences in the expression levels of NFkappaB p50
      subunit. However, NFkappaB p50 levels were significantly decreased (P < 0.05) in
      the pars compacta of the substantia nigra in the DLB cases in comparison with
      controls. The decrease in the expression of the p50 subunit in the substantia
      nigra of DLB cases achieved in the present study may increase the vulnerability
      of the dopaminergic neurones to a possible neurotoxic effect of p65 subunit.
      Thus, normal levels of NFkappaB p65 might be toxic in neurones with a low
      expression of the NFkappaB p50 subunit.

PMID- 17442065
TI  - Remyelination can be extensive in multiple sclerosis despite a long disease
      course.
AB  - Experimental studies using models of multiple sclerosis (MS) indicate that rapid
      and extensive remyelination of inflammatory demyelinated lesions is not only
      possible, but is the normal situation. The presence of completely remyelinated MS
      lesions has been noted in numerous studies and routine limited sampling of post
      mortem MS material suggests that remyelination may be extensive in the early
      stages but eventually fails. However, visual macroscopic guided sampling tends to
      be biased towards chronic demyelinated lesions. Here we have extensively sampled
      cerebral tissue from two MS cases to investigate the true extent of
      remyelination. Sections were cut from 185 cerebral tissue blocks and stained with
      haematoxylin and eosin (H&E), luxol fast blue and cresyl fast violet (LFB/CFV)
      and anti-myelin oligodendrocyte glycoprotein, human leucocyte antigen-DR (HLA-DR)
      and 200 kDa neurofilament protein antibodies. Demyelinated areas were identified
      in 141 blocks, comprising both white matter (WMLs) and/or grey matter lesions. In
      total, 168 WMLs were identified, 22% of which were shadow plaques, 73% were
      partially remyelinated and only 5% were completely demyelinated. The average
      extent of lesion remyelination for all WMLs investigated was 47%. Increased
      density of HLA-DR(+) macrophages and microglia at the lesion border correlated
      significantly with more extensive remyelination. Results from this study of two
      patients with long standing disease suggest that remyelination in MS may be more
      extensive than previously thought.

PMID- 17442066
TI  - Combination of the ALCR/alcA ethanol switch and GAL4/VP16-UAS enhancer trap
      system enables spatial and temporal control of transgene expression in
      Arabidopsis.
AB  - The experimental control of gene expression in specific tissues or cells at
      defined time points is a useful tool for the analysis of gene function. GAL4/VP16
      UAS enhancer trap lines can be used to selectively express genes in specific
      tissues or cells, and an ethanol-inducible system can help to control the time of
      expression. In this study, the combination of the two methods allowed the
      successful regulation of gene expression in both time and space. For this
      purpose, a binary vector, 962-UAS::GUS, was constructed in which the ALCR
      activator and beta-glucuronidase (GUS) reporter gene were placed under the
      control of upstream activator sequence (UAS) elements and the alcA response
      element, respectively. Three different GAL4/VP16-UAS enhancer trap lines of
      Arabidopsis were transformed, resulting in transgenic plants in which GUS
      activity was detected only on ethanol induction and exclusively in the predicted
      tissues of the enhancer trap lines. As a library of different enhancer trap lines
      with distinct green fluorescent protein (GFP) patterns exist, transformation with
      a similar vector, in which GUS is replaced by another gene, would enable the
      control of the time and place of transgene expression. We have constructed two
      vectors for easy cloning of the gene of interest, one with a polylinker site and
      one that is compatible with the GATEWAY vector conversion system. The method can
      be extended to other species when enhancer trap lines become available.

PMID- 17442067
TI  - Subclinical rejection and sirolimus associated edema in renal allograft
      recipients.

PMID- 17442068
TI  - Possible therapeutic effect of lipid supplementation on neurological
      complications in liver transplant recipients.
AB  - Neurological complications (NCs) represent a serious problem following liver
      transplantation and may develop either because of various peri-operative factors
      or the toxicity of immunosuppression. Although the causality assessment of NCs
      can be particularly difficult in the setting of organ transplantation,
      calcineurin inhibitors (CNIs) might influence NCs to a certain extent, regardless
      of the etiology. Therefore, minimizing the influence of CNIs could be a
      reasonable strategy for alleviating NCs. Based on our hypothesis that lipid
      supplementation prevents lipophilic CNIs from crossing the blood-brain barrier,
      soybean oil was administered to five liver transplant patients with NCs. In all
      of these patients, the neurological symptoms improved without discontinuing or
      reducing the dose of CNIs. Thus, lipid supplementation might be able to reduce
      the adverse neurological effects of CNIs.

PMID- 17442069
TI  - The purse-string suture revisited: a useful technique for the closure of
      cutaneous surgical wounds.
AB  - The purse-string suture provides complete or partial closure of round
      postoperative skin defects. It is a rapid and simple procedure to perform.
      Tension placed on the suture uniformly advances the skin from the entire
      periphery of the wound, resulting in a significant reduction of the defect size
      and enhancement of hemostasis at the wound edge. The history, modifications of
      the technique, advantages, and potential complications of the purse-string suture
      are reviewed. It is not only useful following the removal of nonmelanoma skin
      cancer but also after the local excision of melanoma. In addition, this technique
      is especially suitable for the repair of round surgical wounds for patients who
      are unable to modify their active lifestyles during the week following surgery,
      individuals concurrently being treated with anticoagulants, antiplatelet agents
      or both, and people with extensive postoperative defects that would otherwise
      require either a skin graft or a large cutaneous flap. Typically, the site of the
      surgical wound following partial or complete closure with the purse-string suture
      demonstrates excellent long-term cosmetic and functional results.

PMID- 17442070
TI  - Clinicopathologic challenge.

PMID- 17442071
TI  - Turkish version of Skindex-29.
AB  - BACKGROUND: There is a clear need for a useable measure of health-related quality
      of-life (HRQoL) for dermatology patients. Most of the existing dermatology
      specific measures were developed for the English language, and these measures
      should be adapted for use in other cultures. OBJECTIVE: To adapt Skindex-29 (one
      of the most widely recognized dermatology-specific quality-of-life indices) for
      the Turkish cultural setting. PATIENTS AND METHODS: Forward and backward
      translations were carried out, and for doubtful items the process was repeated
      until a satisfactory agreement with the original version of Skindex-29 was
      achieved. The intermediate Turkish version was administered to a group of 20
      randomly selected Turkish adults with and without skin conditions. The final
      Turkish version of the Skindex-29 was administered to 456 patients attending
      Osmangazi University Dermatology outpatient clinics. Reliability, construct and
      content validity were assessed. RESULTS: The instrument was internally
      consistent, with Cronbach's alpha-coefficients of 0.94, 0.76, 0.88, and 0.92 for
      entire questionnaire, symptom, emotional, and functional scales, respectively.
      The Turkish Skindex-29 demonstrated construct and content validity. CONCLUSION:
      Our evaluation of the Skindex-29 indicates that the instrument is a
      comprehensible, useable, reliable and valid measure of quality-of-life for
      Turkish dermatologic patients.

PMID- 17442072
TI  - Epidemiologic survey of pemphigus vulgaris with oral manifestations in northern
      Greece: retrospective study of 129 patients.
AB  - OBJECTIVE: To evaluate the epidemiology of pemphigus vulgaris (PV) in a Greek
      population and to compare it with other countries. MATERIALS AND METHODS: A
      retrospective study was conducted based on the records of 129 patients (41 males
      and 88 females) with PV who visited the Department of the Oral Medicine and
      Maxillofacial Pathology, Aristotle University of Thessaloniki, Greece and the
      State Hospital for Skin and Venereal Diseases of Thessaloniki, Greece, between
      1985 and 2004. A group of 73 individuals was used as controls. RESULTS: The
      average annual incidence was found to be eight patients per year. The male to
      female ratio was 1 : 2.25. The difference in the age of onset between the two
      genders was statistically significant in marginal levels (P = 0.05). In addition,
      86.1% of the patients showed oral lesions only, 13.3% oral and skin lesions and
      1.3% manifested oral, skin, and ocular lesions. Twenty-eight of the 88 females
      were in the premenopausal period-of-life. Additionally, 19 males were farmers who
      had daily contact with organophosphoric pesticides. Co-existing pathologic
      conditions were present in 75 of the 129 patients, and of these 75 patients six
      (8%) were diabetics, 15 (20%) presented with hypertension, two (2.6%) faced
      problems from their thyroid gland, and 10 (13.3%) of the patients complained of
      allergic reactions. CONCLUSIONS: The results of this study demonstrated a
      relatively high incidence of PV in northern Greece compared with that in other
      countries. The disease most frequently occurred in the sixth decade-of-life and
      the majority of the patients manifested oral lesions. Further epidemiological
      studies are needed to elucidate whether this region is constituted from
      population groups with high susceptibility to PV.

PMID- 17442073
TI  - Risk factors for chickenpox incidence in Taiwan from a large-scale computerized
      database.
AB  - OBJECTIVE: We analyzed data from the National Health Insurance Research (NHIR)
      database in the year 2000 to estimate the seasonal variation in the chickenpox
      rate in Taiwan. PATIENTS AND METHODS: All chickenpox cases listed in the NHIR
      database were included (n = 165,719). A Lorenz curve was plotted and a chi-square
      test for equal proportions calculated for seasonal variation. To determine the
      effects of temperature and season on outcome values, generalized estimating
      equation methods were utilized to adjust the effects of other possible
      influencing factors and take into account the within-subject dependence over
      repeated assessments. RESULTS: All four regions of the country had highest
      incidence rates in January, and three of them had lowest rates in September.
      Incidence was significantly higher in females aged 15-24 years than in males. An
      increment of 1 degrees C resulted in an incidence ratio of approximately 0.98 or,
      equivalently, a 10 degrees C increment gives an incidence ratio of approximately
      0.78. CONCLUSION: The results suggest that season and temperature are
      significantly related to the incidence of chickenpox. Infectious diseases can be
      monitored. Prevention procedures can be taken by understanding its pattern and
      activity in order to decide the best policy for vaccination. Further studies are
      warranted, particularly for long-term trends, and in other nations with different
      seasonal temperatures from Taiwan.

PMID- 17442074
TI  - Generalized pruritus treated with narrowband UVB.
AB  - BACKGROUND: Narrowband UVB phototherapy has been increasingly used in a variety
      of dermatological diseases. We planned to evaluate its efficacy in generalized
      pruritus in this prospective study. METHODS: Forty-six patients were included and
      then divided into two groups: group 1 and group 2 consisted of patients with
      uremic pruritus and "idiopathic pruritus", respectively. Phototherapy was given
      three times a week. Efficacy assessments were made by means of visual analog
      scale (VAS) and pruritus grading score. RESULTS: Thirty-five patients completed
      the treatment. Mean VAS decreased from 8.2 +/- 1.5 to 3.6 +/- 3 in group 1 and
      from 7.1 +/- 2.3 to 2.3 +/- 2.8 in group 2 (P < 0.0001). Mean percentage of
      change in VAS was 54.2% (95% CI 32.6-75.9) and 67.9% (95% CI 53.8-81.9) in group
      1 and group 2, respectively. Mean number of treatments was 22 in both groups.
      Mean cumulative UVB dose was 24,540 mJ/cm(2) and 20,801 mJ/cm(2) in group 1 and
      group 2, respectively. CONCLUSION: Narrowband UVB is an effective and well
      tolerated treatment option for patients with generalized pruritus.

PMID- 17442075
TI  - Spectrophotometric intracutaneous analysis in the diagnosis of basal cell
      carcinoma: a pilot study.
AB  - BACKGROUND: The SIAscope is a portable imaging device that uses a hand-held unit
      to emit light of varying wavelengths when placed on the skin. The components of
      skin absorb light to known extents and any reflected light is received by the
      hand-held unit. This information is processed by the SIAscope software to produce
      images on a computer screen, displaying the melanin, blood, and collagen in the
      area of concern. Hypothesis/aims Previous research has shown the SIAscope to be
      both highly sensitive and specific for melanoma diagnosis. The SIAscope has not,
      however, been previously investigated for nonmelanoma skin cancer diagnosis. We
      therefore conducted a pilot study to investigate such potential. METHODS: Having
      gained ethical approval, 20 consecutive lesions were scanned using the SIAscope,
      and the images were examined for features that may be indicative of nonmelanoma
      skin cancer. RESULTS: The findings of branched vessels and vascular "flare" were
      indicative of a lesion being a basal cell carcinoma. Focal paleness and collagen
      changes were less specific in this study, but may prove to be valuable features
      in further studies. CONCLUSIONS: This pilot study implies that the SIAscope may
      indeed provide an accurate method for basal cell carcinoma diagnosis by
      identifying features specific for such lesions. Further studies to investigate
      nonmelanoma skin cancer diagnosis, and to explore any potential to differentiate
      between basal cell carcinomas and squamous cell carcinomas and between
      superficial and thicker basal cell carcinomas by the SIAscope, are warranted.

PMID- 17442076
TI  - Odontogenic focal infection could be partly involved in the pathogenesis of
      atopic dermatitis as exacerbating factor.
AB  - BACKGROUND: A focal infection has been reported to be associated with the
      pathogenesis of various skin diseases, but, to date, not atopic dermatitis (AD).
      The objective of the study was to clarify whether the odontogenic focal infection
      (OFI) could be recognized as one of the exacerbating factors in AD. METHODS:
      Forty-three patients with AD whose skin conditions were resistant to conventional
      therapy were examined. An OFI was evaluated by using radiographs. Serum IgE/sCD30
      levels were also examined. Skin condition was evaluated by the eczema area and
      severity index (EASI). RESULTS: Odontogenic focal infection was detected in 13
      patients (30%) and this incidence was higher than in the normal population.
      Moreover, a 3-month therapy including dental care improved the skin conditions of
      patients with OFI better than those without OFI. CONCLUSION: The study concluded
      that OFI could be involved in the pathogenesis of some types of AD as
      exacerbating factors.

PMID- 17442077
TI  - The emergence of mucormycosis as an important opportunistic fungal infection:
      five cases presenting to a tertiary referral center for mycology.
AB  - BACKGROUND: Mucormycosis, a rare opportunistic fungal infection, is re-emerging
      in importance with the increase in prevalence of immunosuppressive states, both
      as a result of therapy and disease. METHODS: We report five cases of mucormycosis
      diagnosed by the Dermatology Department and managed jointly with the Medical and
      Surgical Services of "Dr Manuel Gea Gonzalez" General Hospital in Mexico City, a
      tertiary referral center for mycology. We also review the current literature
      including recent advances in medical therapy. RESULTS: Four of the five cases
      were of the rhino-orbital-cerebral variant, commonly associated with significant
      mortality, and one of these patients died despite early diagnosis and aggressive
      management. The fifth case was primary cutaneous mucormycosis and this patient
      survived infection without relapse. Diabetic ketoacidosis predisposed to
      infection in four cases and the other was associated with advanced human
      immunodeficiency virus infection. Radiologic imaging was important in cases of
      facial involvement in order to evaluate the extent of disease and possible
      intracranial involvement. All cases were managed with systemic antifungals and
      surgical debridement, together with the treatment of predisposing factors.
      CONCLUSIONS: These cases illustrate the need for early clinical recognition and
      prompt therapy, as well as the requirement for tissue biopsy in order to
      demonstrate the characteristic morphologic features of this fungal agent in the
      absence of positive mycology culture results. This report also highlights that,
      although rhino-orbital-cerebral mucormycosis requires effective multidisciplinary
      management, the disease not uncommonly presents to dermatologists for diagnosis.

PMID- 17442078
TI  - First case of typical Old World cutaneous leishmaniasis treated with miltefosine.
AB  - A 26-year-old man presented to our clinic for advice on treatment options
      regarding cutaneous leishmaniasis (CL) with multiple lesions. The biopsy revealed
      Leishmania amastigotes; Leishmania major was identified by polymerase chain
      reaction (PCR).(11 )Leishmania serology (indirect immunofluorescence test) was
      positive at 1 : 160 (normal, < or = 1 : 40). Ten weeks earlier, the patient had
      spent a 1-week biking holiday in central Tunisia. Two weeks after returning to
      Germany, he noticed the flaring up of multiple insect bites (> 40) contracted in
      Tunisia on both arms. The lesions increased in size and axillary lymph node
      enlargement occurred. Some of the nodular lesions disappeared spontaneously and
      some increased in size and showed central ulceration. When we first saw the
      patient, he had six lesions on his right arm and one on his left arm. The largest
      lesion was on the dorsum of the right hand (Fig. 1) and showed an indurated edge
      and central ulceration. Before starting systemic treatment, the patient decided
      to wait a few weeks in case spontaneous improvement occurred. However, 8 weeks
      later, the ulceration had further increased in size (Fig. 2) from a diameter of 2
      cm initially to a diameter of 5 cm. Regional lymphatic spread with palpable
      nodules along the adjacent lymphatic vessel had occurred. With the patient's
      informed consent, treatment with oral miltefosine, according to his body weight
      of 96 kg, was started at 50 mg three times daily for 28 days. The treatment was
      well tolerated without any subjective side-effects reported. Liver enzymes, serum
      creatinine, and urea were monitored during treatment. There was a mild increase
      in liver enzymes during the third week of treatment: aspartate aminotransferase
      (AST), 49 U/L (normal, < 35 U/L); alanine aminotransferase (ALT), 107 U/L
      (normal, < 45 U/L); this resolved spontaneously. Ten days after completion of
      treatment, the rolled edge had disappeared and the central ulcer had almost
      healed (Fig. 3). Figure 4 shows the lesion 5 months after completion of
      treatment.

PMID- 17442079
TI  - Mycotic cysts: report of 21 cases including eight pheomycotic cysts from Saudi
      Arabia.
AB  - BACKGROUND: Mycotic cysts are subcutaneous cystic granulomas caused by either
      dematiaceous (pigmented) fungi (pheomycotic cysts) or eumycotic (nonpigmented
      fungi) present in soil, wood, and decaying plant material. These fungi gain
      access to the tissues via a wooden splinter or thorn. No deep tissue involvement
      or extension to bone is known to occur. METHODS: We reviewed our surgical
      pathology files for the last 32 years. All cases with the diagnosis of cysts with
      fungi, thorns, or splinters and associated granulomatous and acute inflammation
      were reviewed. Gomori's silver and periodic acid-Schiff stains were performed in
      all cases. RESULTS: Twenty-one cases of mycotic cyst were found, including eight
      pheomycotic cysts (one with a recurrent lesion seen 11 months after the initial
      excision of the cyst). Thirteen cysts had nonpigmented fungal hyphae. There were
      14 males and seven females, with an age range of 5-76 years. The dorsum of the
      foot was the most frequently affected site (12 cases). Four cases involved the
      fingers, two involved the knee area, two involved the big toe, and one each
      involved the leg, ankle, and forearm. The cysts measured 0.6-4.5 cm in diameter.
      Histologically, there was granulomatous inflammation with a variable degree of
      neutrophilic infiltrate giving central abscess formation. Twelve cases showed a
      wooden splinter. All cases were positive for fungal organisms, mostly septate
      hyphae and spores that were highlighted by special stains. Fungal pigment,
      ranging from yellow-brown to light brown to black, was observed in eight cases.
      No extension to deep tissues was noted. The clinical impression varied widely
      including ganglion, sebaceous cyst, giant cell tumor of the tendon sheath, and
      lipoma. One patient was immunosuppressed following renal transplantation. All
      patients were treated by simple excision. No antifungal chemotherapy was needed
      or administered in any of the patients. One patient had a recurrence of his
      lesion within 1 year as a result of inadequate initial excision. A second re
      excision was curative. CONCLUSION: Mycotic cysts are uncommonly encountered
      lesions that can be easily missed, especially in cases with scant fungal
      elements, thus requiring special stains to detect the organisms. We reported 21
      cases of mycotic cyst, including eight pheomycotic cysts, with emphasis on the
      histopathologic recognition of this unusual entity.

PMID- 17442080
TI  - Melanoma clitoridis.

PMID- 17442081
TI  - Granulosis rubra nasi.
AB  - An 18-year-old man presented with erythematous lesions over the nose of 1 year's
      duration without sensitivity to sunlight. He was otherwise well and there was no
      relevant family history. Physical examination showed excessive sweating of the
      nose, cheeks, and upper lip, and erythema of the nose covered by beads of sweat
      and vesicles (Fig. 1). The rest of the physical examination was normal. The skin
      biopsy showed a discrete mononuclear cell perivascular infiltrate.

PMID- 17442082
TI  - Systemic manifestations of Cheyletiella infestation in man.

PMID- 17442083
TI  - A case of keratitis-ichthyosis-deafness (KID) syndrome.
AB  - A 26-year-old Japanese woman was referred to our hospital with generalized
      hyperkeratosis associated with keratitis and a hearing defect. The patient was
      born from nonconsanguineous parents. Her skin was moderately hyperkeratotic at
      birth. During childhood, the thickness of the skin increased progressively.
      Bilateral sensorineural deafness was recognized at the age of 3 years. Visual
      disturbance was noted in later childhood, and corneal transplantations to the
      right eye were performed twice at the age of 16 and 25 years, but did not improve
      her visual acuity. There was no family history of similar disease. On physical
      examination, the patient showed erythematous, keratotic, scaly plaques on the
      cheeks, auricles, and perioral area (Fig. 1a). A grainy, spiculated,
      hyperkeratotic papillomatosis was particularly marked on the palms and the edge
      of the feet (Fig. 1b,c). The nails were slight hypertrophic, but not dystrophic.
      Ophthalmologic examination revealed the loss of eyebrows and eyelashes and
      hyperkeratotic lesions of the eyelids (Fig. 1d). Corneal opacification was
      observed in the right eye. Conjunctivitis and blepharitis with photophobia were
      also observed in both eyes (Fig. 1d,e). A skin biopsy specimen from the right
      lower thigh showed basket-wave hyperkeratosis and papillomatosis of the
      epidermis. Hyperkeratotic plugs were not observed (Fig. 1f). Laboratory data,
      including complete blood cell count, sedimentation rate, immunoglobulins and
      transaminases, urea, cholesterol, and triglycerides were normal. With informed
      consent, genomic DNA was extracted from blood samples. The complete open reading
      frame of the GJB2 gene was polymerase chain reaction amplified and sequenced. A
      transition mutation (148G --> A) was detected, resulting in a putative amino acid
      change from aspartic acid to asparagine at codon 50 (Fig. 2). The mutation was
      not present in her parents or two siblings. These clinical, pathologic, and
      genetic data supported the diagnosis of keratitis-ichthyosis-deafness syndrome.

PMID- 17442084
TI  - Keratitis-ichthyosis-deafness (KID) syndrome with squamous cell carcinoma.

PMID- 17442085
TI  - First report of a fibro-adenoma in axillary mammary tissue of a renal transplant
      patient taking cyclosporin.

PMID- 17442086
TI  - Plica neuropathica in a 2-year-old boy.
AB  - Plica neuropathica is a rare acquired condition of sudden onset characterized by
      irreversible tangling of hair. It is sparsely reported in the literature, though
      it does not seem to be uncommon, at least in Hindu-religious persons of India.
      However, it has not been previously reported in patients as young as 2 years of
      age, and consequently this fact warranted reporting.

PMID- 17442087
TI  - Subcutaneous phaeohyphomycosis caused by Alternaria alternata in an
      immunocompetent patient.

PMID- 17442088
TI  - Dermatoscopy of pigmented actinic keratosis--a striking similarity to lentigo
      maligna.
AB  - BACKGROUND: Pigmented actinic keratosis (PAK) resembles lentigo maligna (LM)
      clinically and histopathologically in some cases. OBJECTIVES: To describe the
      dermatoscopical characteristics of this uncommon variant of actinic keratosis and
      evaluate whether these characteristics show common features with LM.
      OBSERVATIONS: We had the opportunity to examine a 78-year-old woman who presented
      with a PAK lesion on her face dermatoscopically and histopathologically. The
      pigmented pseudo-network had black and gray dust in some areas, which were the
      main dermatoscopical features. The pigmented pseudo-network was formed by an
      unhomogenous brown background interrupted by regularly distributed hair
      follicules. The hyperpigmentation was based not only on an increased presence of
      melanin within the keratinocytes in the basal and spinous layers of epidermis,
      but also an intensive apoptosis of keratinocytes connected to numerous
      melanophages. CONCLUSIONS: The dermatoscopical picture of PAK in this patient was
      practically indistinguishable from the early stage of LM. The authors considered
      that the pigmented atypical melanocytes' role in LM presenting as black dots in
      the dermatoscopical picture was displayed by the individually pigmented
      keratinocytes in PAK. The groups of melanophages presenting as gray dust were
      present in PAK similarly to their presentation in LM. The character of the
      pigmented pseudo-network is the same in the both afflictions. There is a need to
      examine other cases of PAK in order to decide whether our case represents a
      general pattern of the dermatoscopical picture.

PMID- 17442089
TI  - "Composite graft": a simple option for nasal lining.
AB  - BACKGROUND: We present our experience in the reconstruction of full-thickness
      losses of the substance of the nose using a forehead flap and a composite graft
      (taken from the anterior surface of the concha and adequately shaped) as both
      support and endonasal lining. This technique has never been described for the
      reconstruction of large full-thickness losses of the substance of the nose. The
      donor site of the composite graft in the concha is repaired by a Masson
      retroauricular flap. METHODS: This technique was used on 14 patients (age range,
      52-92 years) after full-thickness excision of tumors of the distal third of the
      nose. Follow-up was from 1 to 4 years. All the composite grafts were
      revascularized. RESULTS: The results obtained were stable over time, and
      rhinoscopy, carried out 6 months after the operation, confirmed a homogeneous
      aspect and a perfect integration of the graft in the residual mucosa.
      CONCLUSIONS: The use of a composite graft for internal lining and a forehead flap
      for external skin allowed is to obtain good results with minimal retraction. This
      technique is simple, fast and almost free of side effects.

PMID- 17442090
TI  - A comparison of botanical and synthetic substances commonly used to prevent head
      lice (Pediculus humanus var. capitis) infestation.
AB  - BACKGROUND: Pediculosis, caused by head lice (Pediculidae: Pediculus humanus var.
      capitis), is experiencing a global resurgence, with the prevalence in primary
      schools averaging as high as 40% in some areas regardless of socioeconomic
      factors. Control efforts using chemical treatments are becoming increasingly
      ineffective, with insecticide resistance recorded in several countries.
      Prevention using repellents and oils would be useful if they limited
      transmission. Many commercially available substances reputedly have effective
      repellent qualities, but remain untested. METHODS: This study tested the
      preventative efficacy of N,N-diethyl-3-methylbenzamide (DEET) against several
      commercially available botanicals to clarify their value as transmission
      inhibitors, irritants, repellents, and antifeedants. RESULTS: The transfer of
      head lice to treated hairs was limited by the slippery nature of the oils rather
      than their repellent qualities. Irritancy was not important because lice
      proceeded despite being highly irritated, except in the case of coconut. Tea tree
      and peppermint caused the most repellence, and tea tree and lavender prevented
      some blood feeding on treated skin. Comparatively, tea tree oil was most
      efficacious, with DEET ranking equal second overall with coconut, peppermint, and
      a botanical mixture. CONCLUSIONS: Neither DEET nor any of the botanicals tested
      showed sufficient preventative efficacy to be endorsed.

PMID- 17442091
TI  - Topical zinc oxide vs. salicylic acid-lactic acid combination in the treatment of
      warts.
AB  - BACKGROUND: Warts are a common dermatologic problem. Treatment is painful,
      prolonged, and can cause scarring. OBJECTIVE: To evaluate topical zinc oxide for
      the treatment of warts. METHODS: This was a randomized, double-blind controlled
      trial of 44 patients. Twenty-two patients were given topical zinc oxide 20%
      ointment, and the other 22 received salicylic acid 15% + lactic acid 15% ointment
      twice daily. All patients were followed up for 3 months or until cure, whichever
      occurred first. All patients were observed for side-effects. RESULTS: Sixteen
      patients in the zinc group and 19 in the salicylic acid-lactic acid group
      completed the study. In the zinc oxide-treated group, 50% of the patients showed
      complete cure and 18.7% failed to respond, compared with 42% and 26%,
      respectively, in the salicylic acid-lactic acid-treated group. No patients
      developed serious side-effects. CONCLUSION: Topical zinc oxide is an efficacious,
      painless, and safe therapeutic option for wart treatment.

PMID- 17442092
TI  - Livedoid vasculopathy and hypercoagulability in a patient with primary Sjogren's
      syndrome.
AB  - BACKGROUND: A 31-year-old woman presented with a 5-year history of painful
      ulcerations, palpable purpura, porcelain-white atrophic scars of the malleolar
      region and dorsal aspect of the feet, livedo reticularis on the limbs,
      arthralgia, xerophthalmia, and xerostomia. METHODS: Skin biopsy revealed vessel
      wall hyalinization and thrombosis of the microvasculature with a very scarce
      dermal inflammatory infiltrate. Biopsy of the oral mucosa showed mononuclear
      infiltration of an intralobular duct of a salivary gland. RESULTS: Laboratory
      studies, including autoantibodies and inflammation markers, were normal, except
      for a positive rheumatoid factor. Coagulation screening revealed C677T
      methylenetetrahydrofolate reductase (MTHFR) mutation, with a normal serum
      homocysteine. The patient was treated with oral methylprednisolone (32 mg/day
      with progressive reduction) and enoxaparin (20 mg/day subcutaneously), with
      complete ulcer healing within 4 months. CONCLUSION: Livedoid vasculitis or
      vasculopathy has not been referred to previously in association with Sjogren's
      syndrome, but may be associated with other autoimmune disorders and anomalies of
      coagulation, namely factor V Leiden mutation, protein C deficiency, and MTHFR
      mutation, associated or not with hyperhomocysteinemia, a condition that seems to
      confer an increased risk of recurrent arterial and venous thrombosis. We stress
      the importance of anticoagulant therapy for ulcer healing and for the prevention
      of other thrombotic events.

PMID- 17442093
TI  - Interferon-alpha is effective for CD4(+), CCR4(-) mycosis fungoides.
AB  - Mycosis fungoides (MF), a cutaneous T-cell lymphoma, is usually characterized by
      cell features of T-helper-2 (Th2) lymphocytes. MF has recently been reported to
      show increased CCR4 expression, a chemokine receptor specifically expressed in
      Th2. Previously, we have reported the effectiveness of interferon-gamma (IFN
      gamma) for the treatment of CCR4(+) MF. In this report, we describe two cases of
      CD4(+), CCR4(-) MF successfully treated with IFN-alpha, but not IFN-gamma.
      Although MF usually displays a Th2 profile, the tumor cells in our two cases did
      not express CCR4. Our cases suggest the effectiveness of IFN-alpha, but not IFN
      gamma, for CCR4- MF.

PMID- 17442096
TI  - Retroviral activation of the mir-106a microRNA cistron in T lymphoma.
AB  - Retroviral insertion into a host genome is a powerful tool not only for the
      discovery of cancer genes, but also for the discovery of potential oncogenic
      noncoding RNAs. In a large-scale mouse T lymphocyte tumor screen we found a high
      density of integrations upstream of the mir-106a microRNA cistron. In tumors
      containing an integration, the primary transcript encoding the mir-106a cistron
      was overexpressed five to 20-fold compared with that of control tumors;
      concomitantly, the mature mir-106a and mir-363 microRNAs were highly
      overexpressed as well. These findings suggest the mir-106a cistron plays an
      important role in T cell tumorigenesis.

PMID- 17442097
TI  - Developments in the synovial biology field 2006.
AB  - Synovial pathophysiology is a complex and synergistic interplay of different cell
      populations with tissue components, mediated by a variety of signaling
      mechanisms. All of these mechanisms drive the affected joint into inflammation
      and drive the subsequent destruction of cartilage and bone. Each cell type
      contributes significantly to the initiation and perpetuation of this deleterious
      concert, especially in rheumatoid arthritis. Rheumatoid arthritis synovial
      fibroblasts and macrophages, both cell types with pivotal roles in inflammation
      and destruction, but also T cells and B cells are crucial for complex network in
      the inflamed synovium. An even more complex cellular crosstalk between these key
      players maintains a process of chronic inflammation. As outlined in the present
      review, in the past year substantial progress has been made to elucidate further
      details of the rich pathophysiology of rheumatoid arthritis, which may also
      facilitate the identification of novel targets for future therapeutic strategies.

PMID- 17442098
TI  - Is bronchoalveolar lavage with quantitative cultures a useful tool for diagnosing
      ventilator-associated pneumonia?
AB  - The results of a recently published Canadian study suggest that bronchoalveolar
      lavage and endotracheal aspiration are associated with similar clinical outcomes
      and similar overall use of antibiotics in critically ill patients with suspected
      ventilator-associated pneumonia (VAP). The study, however, does not provide
      convincing information on the best strategy to diagnose VAP, to accurately choose
      initial treatment and to exclude VAP in order to avoid administering antibiotics
      to patients without bacterial infection. In fact, this trial has several
      limitations or drawbacks: patients at risk for developing VAP due to Pseudomonas
      aeruginosa or methicillin-resistant Staphylococcus aureus were excluded, far from
      the real-life scenario; a significant number of patients were receiving recent
      antimicrobial therapy at the time of sampling, with, consequently, difficult-to
      interpret culture results; randomization of included patients for initial
      treatment - meropenem plus ciprofloxacin or meropenem alone - resulted in a high
      rate of inappropriate initial empirical therapy due to the absence of
      customization to local epidemiology; and the initial decision to treat and the re
      evaluation at day 3 were, in fact, based on clinical judgment and not on direct
      examination and quantitative culture results. In summary, because antimicrobial
      treatment was initiated in all suspected patients and was rarely withheld in
      patients with negative cultures, the study does not suggest an appropriate
      strategy for improving the use of antibiotics in intensive care unit patients.
      Such a strategy has two requirements: immediate administration of adequate
      therapy in patients with true VAP, and avoidance of administering antibiotics in
      patients without bacterial infection.

PMID- 17442099
TI  - Immunization with HIV protease peptides linked to syngeneic erythrocytes.
AB  - New potent vaccine adjuvants are desirable for increasing the efficacy of novel
      vaccine modalities such as DNA and peptides. We therefore tested if syngeneic
      erythrocytes could serve as delivery vectors for selected HIV peptides and
      compared the potency of these constructs to immunization with peptides in
      phosphate buffered saline or in incomplete Freunds adjuvant. Immunization of mice
      with peptides in a low dose (5 ng) coupled to erythrocytes induced a weak immune
      response in mice. These peptides alone (5 microg) gave no immune responses, while
      formulating the peptides (50 microg) in IFA induced strong homologous immunity as
      well as prominent cross reactivity to a related mutant epitope. Thus, vaccine
      delivery using syngeneic erythrocytes, although attractive for clinical use,
      might be of limited value due to the low amount of antigen that can be loaded per
      erythrocyte.

PMID- 17442100
TI  - Safety and efficacy of a caspofungin-based combination therapy for treatment of
      proven or probable aspergillosis in pediatric hematological patients.
AB  - BACKGROUND: Fungal infections are diagnosed increasingly often in patients
      affected by hematological diseases and their mortality has remained high. The
      recent development of new antifungal drugs gives the clinician the possibility to
      assess the combination of antifungal drugs with in-vitro or in animal-model
      synergistic effect. METHODS: We analyzed retrospectively the safety and efficacy
      of caspofungin-based combination therapy in 40 children and adolescents, most of
      them were being treated for a malignant disease, who developed invasive
      aspergillosis (IA) between November 2002 and November 2005. RESULTS: Thirteen
      (32.5%) patients developed IA after hematopoietic stem cell transplantation
      (HSCT), 13 after primary diagnosis, usually during remission-induction
      chemotherapy, and 14 after relapse of disease. Severe neutropenia was present in
      31 (78%) out of the 40 patients. IA was classified as probable in 20 (50%) and
      documented in 20 (50%) patients, respectively. A favorable response to antifungal
      therapy was obtained in 21 patients (53%) and the probability of 100-day survival
      was 70%. Different, though not significant, 100-day survival was observed
      according to the timing of diagnosis of IA: 51.9% after HSCT; 71.4% after
      relapse; and 84.6% after diagnosis of underlying disease, p 0.2. After a median
      follow-up of 0.7 years, 20 patients are alive (50%). Overall, the combination
      therapy was well tolerated. In multivariate analysis, the factors that were
      significantly associated to a better overall survival were favorable response to
      antifungal therapy, p 0.003, and the timing of IA in the patient course of
      underlying disease, p 0.04. CONCLUSION: This study showed that caspofungin-based
      combination antifungal therapy is an effective therapeutic option also for
      pediatric patients with IA. These data need to be confirmed by prospective,
      controlled studies.

PMID- 17442101
TI  - Autoinducer production and quorum-sensing dependent phenotypes of Pseudomonas
      aeruginosa vary according to isolation site during colonization of intubated
      patients.
AB  - BACKGROUND: Pseudomonas aeruginosa frequently colonizes and is responsible for
      severe ventilator-associated pneumonia in intubated patients. A quorum-sensing
      (QS) circuit, depending on the production of the two QS-signaling molecules
      (autoinducers, AIs) 3-oxo-C12-HSL and C4-HSL, regulates the production by P.
      aeruginosa of several virulence factors and is required for biofilm formation.
      Therefore QS-inhibition has been suggested as a new target for preventive and/or
      therapeutic strategies. However the precise role of QS during colonization and
      subsequent infections of intubated patients remains unclear. RESULTS: We wondered
      whether QS is active during colonization of intubated patients, and whether P.
      aeruginosa isolates growing inside the biofilm covering the intubation devices
      and those resident in the lungs of colonized patients differ in their QS
      dependent phenotypes. We collected the intubation devices of eight patients
      colonized by P. aeruginosa. We detected 3-oxo-C12-HSL on eight, and C4-HSL on six
      of these devices. In three of these patients we also obtained P. aeruginosa
      isolates from tracheal aspirates at the time of extubation (n = 18), as well as
      isolates from the intubation devices (n = 25). We genotyped these isolates,
      quantified their AIs production, and determined three QS-dependent phenotypes
      (adherence capacity, biofilm and elastase production). The production of 3-oxo
      C12-HSL was consistently increased for isolates from the intubation devices,
      whereas the production of C4-HSL was significantly higher for isolates from
      tracheal aspirates. Isolates from tracheal aspirates produced significantly
      higher amounts of elastase but less biofilm, and had a marginally reduced
      adhesion capacity than isolates from the intubation devices. Levels of 3-oxo-C12
      HSL and elastase production correlated statistically for tracheal intubation
      isolates, whereas levels of 3-oxo-C12-HSL production and adhesion ability, as
      well as biofilm production, correlated weakly amongst intubation device isolates.
      CONCLUSION: Our findings demonstrate that autoinducers are produced during the
      colonization of intubated patients by P. aeruginosa. The microenvironment, in
      which P. aeruginosa grows, may select for bacteria with different capacities to
      produce autoinducers and certain QS-dependent phenotypes. QS-inhibition might
      therefore affect differently isolates growing inside the biofilm covering
      intubation devices and those resident in the lungs.

PMID- 17442102
TI  - Detecting microsatellites within genomes: significant variation among algorithms.
AB  - BACKGROUND: Microsatellites are short, tandemly-repeated DNA sequences which are
      widely distributed among genomes. Their structure, role and evolution can be
      analyzed based on exhaustive extraction from sequenced genomes. Several dedicated
      algorithms have been developed for this purpose. Here, we compared the detection
      efficiency of five of them (TRF, Mreps, Sputnik, STAR, and RepeatMasker).
      RESULTS: Our analysis was first conducted on the human X chromosome, and
      microsatellite distributions were characterized by microsatellite number, length,
      and divergence from a pure motif. The algorithms work with user-defined
      parameters, and we demonstrate that the parameter values chosen can strongly
      influence microsatellite distributions. The five algorithms were then compared by
      fixing parameters settings, and the analysis was extended to three other genomes
      (Saccharomyces cerevisiae, Neurospora crassa and Drosophila melanogaster)
      spanning a wide range of size and structure. Significant differences for all
      characteristics of microsatellites were observed among algorithms, but not among
      genomes, for both perfect and imperfect microsatellites. Striking differences
      were detected for short microsatellites (below 20 bp), regardless of motif.
      CONCLUSION: Since the algorithm used strongly influences empirical distributions,
      studies analyzing microsatellite evolution based on a comparison between
      empirical and theoretical size distributions should therefore be considered with
      caution. We also discuss why a typological definition of microsatellites limits
      our capacity to capture their genomic distributions.

PMID- 17442103
TI  - Gain and loss of polyadenylation signals during evolution of green algae.
AB  - BACKGROUND: The Viridiplantae (green algae and land plants) consist of two
      monophyletic lineages: the Chlorophyta and the Streptophyta. Most green algae
      belong to the Chlorophyta, while the Streptophyta include all land plants and a
      small group of freshwater algae known as Charophyceae. Eukaryotes attach a poly-A
      tail to the 3' ends of most nuclear-encoded mRNAs. In embryophytes, animals and
      fungi, the signal for polyadenylation contains an A-rich sequence (often AAUAAA
      or related sequence) 13 to 30 nucleotides upstream from the cleavage site, which
      is commonly referred to as the near upstream element (NUE). However, it has been
      reported that the pentanucleotide UGUAA is used as polyadenylation signal for
      some genes in volvocalean algae. RESULTS: We set out to investigate
      polyadenylation signal differences between streptophytes and chlorophytes that
      may have emerged shortly after the evolutionary split between Streptophyta and
      Chlorophyta. We therefore analyzed expressed genes (ESTs) from three streptophyte
      algae, Mesostigma viride, Klebsormidium subtile and Coleochaete scutata, and from
      two early-branching chlorophytes, Pyramimonas parkeae and Scherffelia dubia. In
      addition, to extend the database, our analyses included ESTs from six other
      chlorophytes (Acetabularia acetabulum, Chlamydomonas reinhardtii, Helicosporidium
      sp. ex Simulium jonesii, Prototheca wickerhamii, Scenedesmus obliquus and Ulva
      linza) and one streptophyte (Closterium peracerosum). Our results indicate that
      polyadenylation signals in green algae vary widely. The UGUAA motif is confined
      to late-branching Chlorophyta. Most streptophyte algae do not have an A-rich
      sequence motif like that in embryophytes, animals and fungi. We observed
      polyadenylation signals similar to those of Arabidopsis and other land plants
      only in Mesostigma. CONCLUSION: Polyadenylation signals in green algae show
      considerable variation. A new NUE (UGUAA) was invented in derived chlorophytes
      and replaced not only the A-rich NUE but the complete poly(A) signal in all
      chlorophytes investigated except Scherffelia (only NUE replaced) and Pyramimonas
      (UGUAA completely missing). The UGUAA element is completely absent from
      streptophytes. However, the structure of the poly(A) signal was often modified in
      streptophyte algae. In most species investigated, an A-rich NUE is missing;
      instead, these species seem to rely mainly on U-rich elements.

PMID- 17442104
TI  - Daptomycin antimicrobial activity tested against methicillin-resistant
      staphylococci and vancomycin-resistant enterococci isolated in European medical
      centers (2005).
AB  - BACKGROUND: Daptomycin is a cyclic lipopeptide with potent activity and broad
      spectrum against Gram-positive bacteria currently used for the treatment of
      complicated skin and skin structure infections and bacteremia, including right
      sided endocarditis. We evaluated the in vitro activity of this compound and
      selected comparator agents tested against clinical strains of staphylococci and
      enterococci collected in European medical centers in 2005. METHODS: A total of
      4,640 strains from 23 medical centers located in 10 European countries, Turkey
      and Israel (SENTRY Program platform) were tested for susceptibility by reference
      broth microdilution methods according to Clinical and Laboratory Standards
      Institute guidelines and interpretative criteria. Mueller-Hinton broth was
      supplemented to 50 mg/L Ca++ for testing daptomycin. Results for oxacillin
      (methicillin)-resistant staphylococci and vancomycin-resistant enterococci were
      analyzed separately. RESULTS: Oxacillin resistance rates among Staphylococcus
      aureus varied from 2.1% in Sweden to 42.5% in the United Kingdom (UK) and 54.7%
      in Ireland (29.1% overall), while vancomycin resistance rates varied from 0.0% in
      France, Sweden and Switzerland to 66.7% in the UK and 71.4% in Ireland among
      Enterococcus faecium (17.9% overall). All S. aureus strains were inhibited at
      daptomycin MIC of 1 mg/L (MIC50/90, 0.25/0.5 mg/L; 100.0% susceptible) and only
      one coagulase-negative staphylococci strain (0.1%) showed an elevated (>1 mg/L)
      daptomycin MIC value (4 mg/L). Among E. faecalis (MIC50/90, 0.5/1 mg/L; 100%
      susceptible) the highest daptomycin MIC value was 2 mg/L; while among E. faecium
      (MIC50/90, 2/4 mg/L; 100% susceptible) the highest MIC result was 4 mg/L.
      CONCLUSION: Daptomycin showed excellent in vitro activity against staphylococci
      and enterococci collected in European medical centers in 2005 and resistance to
      oxacillin, vancomycin or quinupristin/dalfopristin did not compromise its
      activity overall against these pathogens. Based on these results and those of
      previous publications, daptomycin appears to be an excellent therapeutic option
      for serious infections caused by oxacillin-resistant staphylococci and vancomycin
      resistant enterococci in Europe.

PMID- 17442105
TI  - From cat scratch disease to endocarditis, the possible natural history of
      Bartonella henselae infection.
AB  - BACKGROUND: Most patients with infectious endocarditis (IE) due to Bartonella
      henselae have a history of exposure to cats and pre-existing heart valve lesions.
      To date, none of the reported patients have had a history of typical cat scratch
      disease (CSD) which is also a manifestation of infection with B. henselae. CASE
      PRESENTATION: Here we report the case of a patient who had CSD and six months
      later developed IE of the mitral valve caused by B. henselae. CONCLUSION: Based
      on this unique case, we speculate that CSD represents the primary-infection of B.
      henselae and that IE follows in patients with heart valve lesions.

PMID- 17442106
TI  - Human pluripotent embryonal carcinoma NTERA2 cl.D1 cells maintain their typical
      morphology in an angiomyogenic medium.
AB  - BACKGROUND: Pluripotent embryonal carcinomas are good potential models, to study,
      "in vitro," the mechanisms that control differentiation during embryogenesis. The
      NTERA2cl.D1 (NT2/D1) cell line is a well known system of ectodermal
      differentiation. Retinoic acid (RA) induces a dorsal pattern of differentiation
      (essentially neurons) and bone morphogenetic protein (BMP) or
      hexamethylenebisacetamide (HMBA) induces a more ventral (epidermal) pattern of
      differentiation. However, whether these human cells could give rise to mesoderm
      derivatives as their counterpart in mouse remained elusive. We analyzed the
      morphological characteristics and transcriptional activation of genes pertinent
      in cardiac muscle and endothelium differentiation, during the growth of NT2/D1
      cells in an inductive angiomyogenic medium with or without Bone Morphogenetic
      Protein 2 (BMP2). RESULTS: Our experiments showed that NT2/D1 maintains their
      typical actin organization in angiomyogenic medium. Although the beta myosin
      heavy chain gene was never detected, all the other 15 genes analyzed maintained
      their expression throughout the time course of the experiment. Among them were
      early and late cardiac, endothelial, neuronal and teratocarcinoma genes.
      CONCLUSION: Our results suggest that despite the NT2/D1 cells natural tendency to
      differentiate into neuroectodermal lineages, they can activate genes of
      mesodermal lineages. Therefore, we believe that these pluripotent cells might
      still be a good model to study biological development of mesodermal derivatives,
      provided the right culture conditions are met.

PMID- 17442107
TI  - Trends of hepatitis A hospitalization and risk factors in Quebec, Canada, between
      1990 and 2003.
AB  - BACKGROUND: In Canada, targeted vaccination of at risk groups for hepatitis A
      (HA) is done since the mid 1990s resulting in declining incidence. This study
      estimated the year and age specific hospitalization rates and distribution of
      risk factors for HA in Quebec, Canada, between 1990 and 2003. METHODS: Records of
      patients hospitalized with HA-related diagnostic codes were retrieved from the
      provincial database. Hospital charts of all deceased cases and a random sample of
      all other records were reviewed. RESULTS: From 1503 hospitalization records, 573
      charts were reviewed including 49 (91%) of the 54 deceased patients. Confirmed
      acute HA was present in 79% of records where HA was the primary diagnosis, and in
      3%-8% of records where HA was a secondary diagnosis. From the total estimated
      number of hospitalizations, 96% had HA as the primary diagnosis. The
      hospitalization rate decreased from 1.06 per 100 000 person-years between 1990
      and 1997 to 0.36 between 1998 and 2003. During the study period, 54% HA
      hospitalizations were in 20-39 year-olds. The overall case fatality ratio among
      hospitalized patients was 1.4%, increasing from 0.4% in those < 40 years old to
      12.5% in those > or =60 years. By decreasing order, reported risk factors were
      travel to HA endemic countries (30%), MSM (18%) and household contacts (11%).
      CONCLUSION: HA hospitalization rates have been low since 1998 but the cause of
      this is unclear given the cyclical pattern of HA. Travel to endemic countries
      remains the most important risk factor and improved control of HA will require
      better strategies to vaccinate travelers.

PMID- 17442108
TI  - Competency-based evaluation tools for integrative medicine training in family
      medicine residency: a pilot study.
AB  - BACKGROUND: As more integrative medicine educational content is integrated into
      conventional family medicine teaching, the need for effective evaluation
      strategies grows. Through the Integrative Family Medicine program, a six site
      pilot program of a four year residency training model combining integrative
      medicine and family medicine training, we have developed and tested a set of
      competency-based evaluation tools to assess residents' skills in integrative
      medicine history-taking and treatment planning. This paper presents the results
      from the implementation of direct observation and treatment plan evaluation
      tools, as well as the results of two Objective Structured Clinical Examinations
      (OSCEs) developed for the program. METHODS: The direct observation (DO) and
      treatment plan (TP) evaluation tools developed for the IFM program were
      implemented by faculty at each of the six sites during the PGY-4 year (n = 11 on
      DO and n = 8 on TP). The OSCE I was implemented first in 2005 (n = 6), revised
      and then implemented with a second class of IFM participants in 2006 (n = 7).
      OSCE II was implemented in fall 2005 with only one class of IFM participants (n =
      6). Data from the initial implementation of these tools are described using
      descriptive statistics. RESULTS: Results from the implementation of these tools
      at the IFM sites suggest that we need more emphasis in our curriculum on
      incorporating spirituality into history-taking and treatment planning, and more
      training for IFM residents on effective assessment of readiness for change and
      strategies for delivering integrative medicine treatment recommendations.
      Focusing our OSCE assessment more narrowly on integrative medicine history-taking
      skills was much more effective in delineating strengths and weaknesses in our
      residents' performance than using the OSCE for both integrative and more basic
      communication competencies. CONCLUSION: As these tools are refined further they
      will be of value both in improving our teaching in the IFM program and as
      competency-based evaluation resources for the expanding number of family medicine
      residency programs incorporating integrative medicine into their curriculum. The
      next stages of work on these instruments will involve establishing inter-rater
      reliability and defining more clearly the specific behaviors which we believe
      establish competency in the integrative medicine skills defined for the program.

PMID- 17442109
TI  - UbiProt: a database of ubiquitylated proteins.
AB  - BACKGROUND: Post-translational protein modification with ubiquitin, or
      ubiquitylation, is one of the hottest topics in a modern biology due to a
      dramatic impact on diverse metabolic pathways and involvement in pathogenesis of
      severe human diseases. A great number of eukaryotic proteins was found to be
      ubiquitylated. However, data about particular ubiquitylated proteins are rather
      disembodied. DESCRIPTION: To fill a general need for collecting and systematizing
      experimental data concerning ubiquitylation we have developed a new resource,
      UbiProt Database, a knowledge base of ubiquitylated proteins. The database
      contains retrievable information about overall characteristics of a particular
      protein, ubiquitylation features, related ubiquitylation and de-ubiquitylation
      machinery and literature references reflecting experimental evidence of
      ubiquitylation. UbiProt is available at http://ubiprot.org.ru for free.
      CONCLUSION: UbiProt Database is a public resource offering comprehensive
      information on ubiquitylated proteins. The resource can serve as a general
      reference source both for researchers in ubiquitin field and those who deal with
      particular ubiquitylated proteins which are of their interest. Further
      development of the UbiProt Database is expected to be of common interest for
      research groups involved in studies of the ubiquitin system.

PMID- 17442110
TI  - Diabetes, minor depression and health care utilization and expenditures: a
      retrospective database study.
AB  - BACKGROUND: To estimate the prevalence of minor depression among US adults with
      diabetes, health care resource utilization, and expenditures by people with
      diabetes with and without minor depression. METHODS: Among adult 2003 Medical
      Expenditure Panel Survey respondents, diabetes was identified by diagnosis code
      and self-report. Depression was identified by diagnosis code plus > or = one
      antidepressant prescription. Odds of having depression was estimated in people
      with diabetes and the general population, adjusted for sociodemographic variables
      (e.g., age, sex, race/ethnicity). Multivariate regressions evaluated factors
      associated with utilization and log-transformed expenditures for ambulatory care,
      hospitalizations, emergency visits, and prescriptions. RESULTS: In 2003, 1932
      respondents had diabetes, 435/1932 had diabetes and minor depression. Adults with
      diabetes were more likely than the general population to have depression
      (adjusted OR 1.81, 95% CI 1.56, 2.09). People with diabetes with versus without
      comorbid depression were more likely to be women, have lower incomes and health
      status, and more diabetes complications (all p < 0.05). In unadjusted analyses,
      ambulatory care visits were higher for those with versus without depression (17.9
      vs. 11.4, p = 0.04), as were prescriptions (60.7 vs. 38.1, p = 0.05). In adjusted
      analyses, depression was not associated with increased resource use or higher
      expenditures in any category. Increased number of comorbid conditions was
      associated with increased resource use in all categories, and increased
      expenditures for ambulatory care and prescriptions. CONCLUSION: People with
      diabetes are twice as likely to have depression as the general population.
      Screening for and treatment of depression is warranted, as is additional research
      into a causal relationship between diabetes and depression.

PMID- 17442111
TI  - The interferon induced with helicase domain 1 A946T polymorphism is not
      associated with rheumatoid arthritis.
AB  - An important feature of autoimmune diseases is the overlap of pathophysiological
      characteristics. Clustering of autoimmune diseases in families suggests that
      genetic variants may contribute to autoimmunity. The aim of the present study was
      to investigate the role of the interferon induced with helicase domain 1 (IFIH1)
      A946T (rs1990760 A>G) variant in rheumatoid arthritis (RA), as this was recently
      associated with susceptibility to type 1 diabetes. A total of 965 Caucasians with
      RA and 988 healthy controls were genotyped for IFIH1 A946T. Gene expression of
      IFIH1 was measured in peripheral blood leukocytes using real-time PCR. Genotypes
      were equally distributed in both RA cases and healthy controls (odds ratio for
      allele C = 0.9, 95% confidence interval = 0.8-1.0, P = 0.3). No association was
      detected after stratification by sex, age at onset, rheumatoid factor status,
      anti-cyclic citrullinated peptide status or radiological joint damage. Levels of
      IFIH1 mRNA were approximately twofold higher in blood leucocytes of RA cases
      compared with healthy controls (P < 0.0001). These results indicate that the
      IFIH1 is upregulated in RA but that the A946T variant does not contribute
      significantly to the genetic background of RA.

PMID- 17442112
TI  - Sequence, "subtle" alternative splicing and expression of the CYYR1
      (cysteine/tyrosine-rich 1) mRNA in human neuroendocrine tumors.
AB  - BACKGROUND: CYYR1 is a recently identified gene located on human chromosome 21
      whose product has no similarity to any known protein and is of unknown function.
      Analysis of expressed sequence tags (ESTs) have revealed high human CYYR1
      expression in cells belonging to the diffuse neuroendocrine system (DNES). These
      cells may be the origin of neuroendocrine (NE) tumors. The aim of this study was
      to conduct an initial analysis of sequence, splicing and expression of the CYYR1
      mRNA in human NE tumors. METHODS: The CYYR1 mRNA coding sequence (CDS) was
      studied in 32 NE tumors by RT-PCR and sequence analysis. A subtle alternative
      splicing was identified generating two isoforms of CYYR1 mRNA differing in terms
      of the absence (CAG- isoform, the first described mRNA for CYYR1 locus) or the
      presence (CAG+ isoform) of a CAG codon. When present, this specific codon
      determines the presence of an alanine residue, at the exon 3/exon 4 junction of
      the CYYR1 mRNA. The two mRNA isoform amounts were determined by quantitative
      relative RT-PCR in 29 NE tumors, 2 non-neuroendocrine tumors and 10 normal
      tissues. A bioinformatic analysis was performed to search for the existence of
      the two CYYR1 isoforms in other species. RESULTS: The CYYR1 CDS did not show
      differences compared to the reference sequence in any of the samples, with the
      exception of an NE tumor arising in the neck region. Sequence analysis of this
      tumor identified a change in the CDS 333 position (T instead of C), leading to
      the amino acid mutation P111S. NE tumor samples showed no significant difference
      in either CYYR1 CAG- or CAG+ isoform expression compared to control tissues.
      CYYR1 CAG- isoform was significantly more expressed than CAG+ isoform in NE
      tumors as well as in control samples investigated. Bioinformatic analysis
      revealed that only the genomic sequence of Pan troglodytes CYYR1 is consistent
      with the possible existence of the two described mRNA isoforms. CONCLUSION: A new
      "subtle" splicing isoform (CAG+) of CYYR1 mRNA, the sequence and the expression
      of this gene were defined in a large series of NE tumors.

PMID- 17442113
TI  - Algebraic correction methods for computational assessment of clone overlaps in
      DNA fingerprint mapping.
AB  - BACKGROUND: The Sulston score is a well-established, though approximate metric
      for probabilistically evaluating postulated clone overlaps in DNA fingerprint
      mapping. It is known to systematically over-predict match probabilities by
      various orders of magnitude, depending upon project-specific parameters. Although
      the exact probability distribution is also available for the comparison problem,
      it is rather difficult to compute and cannot be used directly in most cases. A
      methodology providing both improved accuracy and computational economy is
      required. RESULTS: We propose a straightforward algebraic correction procedure,
      which takes the Sulston score as a provisional value and applies a power-law
      equation to obtain an improved result. Numerical comparisons indicate
      dramatically increased accuracy over the range of parameters typical of
      traditional agarose fingerprint mapping. Issues with extrapolating the method
      into parameter ranges characteristic of newer capillary electrophoresis-based
      projects are also discussed. CONCLUSION: Although only marginally more expensive
      to compute than the raw Sulston score, the correction provides a vastly improved
      probabilistic description of hypothesized clone overlaps. This will clearly be
      important in overlap assessment and perhaps for other tasks as well, for example
      in using the ranking of overlap probabilities to assist in clone ordering.

PMID- 17442114
TI  - Evolutionary conservation of sequence and secondary structures in CRISPR repeats.
AB  - BACKGROUND: Clustered regularly interspaced short palindromic repeats (CRISPRs)
      are a novel class of direct repeats, separated by unique spacer sequences of
      similar length, that are present in approximately 40% of bacterial and most
      archaeal genomes analyzed to date. More than 40 gene families, called CRISPR
      associated sequences (CASs), appear in conjunction with these repeats and are
      thought to be involved in the propagation and functioning of CRISPRs. It has been
      recently shown that CRISPR provides acquired resistance against viruses in
      prokaryotes. RESULTS: Here we analyze CRISPR repeats identified in 195 microbial
      genomes and show that they can be organized into multiple clusters based on
      sequence similarity. Some of the clusters present stable, highly conserved RNA
      secondary structures, while others lack detectable structures. Stable secondary
      structures exhibit multiple compensatory base changes in the stem region,
      indicating evolutionary and functional conservation. CONCLUSION: We show that the
      repeat-based classification corresponds to, and expands upon, a previously
      reported CAS gene-based classification, including specific relationships between
      CRISPR and CAS subtypes.

PMID- 17442115
TI  - Utilization and expenditures of veterans obtaining primary care in community
      clinics and VA medical centers: an observational cohort study.
AB  - BACKGROUND: To compare VA inpatient and outpatient utilization and expenditures
      of veterans seeking primary care in community-based outpatient clinics (CBOCs)
      and VA medical centers (VAMCs) in fiscal years 2000 (FY00) and 2001. METHODS: The
      sample included 25,092 patients who obtained primary care exclusively from 108
      CBOCs in FY00, 26,936 patients who obtained primary care exclusively from 72
      affiliated VAMCs in FY00, and 11,450 "crossover" patients who obtained primary
      care in CBOCs and VAMCs in FY00. VA utilization and expenditure data were drawn
      from the VA's system-wide cost accounting system. Veteran demographic
      characteristics and a 1999 Diagnostic Cost Group risk score were obtained from VA
      administrative files. Outpatient utilization (primary care, specialty care,
      mental health, pharmacy, radiology and laboratory) and inpatient utilization were
      estimated using count data models and expenditures were estimated using one-part
      or two-part models. The second part of two-part models was estimated using
      generalized linear regressions. RESULTS: CBOC patients had a slightly more
      primary care visits per year than VAMC patients (p < 0.0001), but lower primary
      care costs (-$71, p < 0.0001). CBOC patients had lower odds of one or more
      specialty, mental health, ancillary visits and hospital stays per year, and fewer
      numbers of visits and stays if they had any and lower specialty, mental health,
      ancillary and inpatient expenditures (all, p < 0.0001). As a result, CBOC
      patients had lower total outpatient and overall expenditures than VAMC patients
      (p < 0.0001). CONCLUSION: CBOCs provided veterans improved access to primary care
      and other services, but expenditures were contained because CBOC patients who
      sought health care had fewer visits and hospital stays than comparable VAMC
      patients. These results suggest a more complex pattern of health care utilization
      and expenditures by CBOC patients than has been found in prior studies. This
      study also illustrates that CBOCs continue to be a critical primary care and
      mental health access point for veterans.

PMID- 17442117
TI  - TagSmart: analysis and visualization for yeast mutant fitness data measured by
      tag microarrays.
AB  - BACKGROUND: A nearly complete collection of gene-deletion mutants (96% of
      annotated open reading frames) of the yeast Saccharomyces cerevisiae has been
      systematically constructed. Tag microarrays are widely used to measure the
      fitness of each mutant in a mutant mixture. The tag array experiments can have a
      complex experimental design, such as time course measurements and drug treatment
      with multiple dosages. RESULTS: TagSmart is a web application for analysis and
      visualization of Saccharomyces cerevisiae mutant fitness data measured by tag
      microarrays. It implements a robust statistical approach to assess the
      concentration differences among S. cerevisiae mutant strains. It also provides an
      interactive environment for data analysis and visualization. TagSmart has the
      following advantages over previously described analysis procedures: 1) it is user
      friendly software rather than merely a description of analytical procedure; 2) It
      can handle complicated experimental designs, such as multiple time points and
      treatment with multiple dosages; 3) it has higher sensitivity and specificity; 4)
      It allows users to mask out "bad" tags in the analysis. Two biological tests were
      performed to illustrate the performance of TagSmart. First, we generated
      titration mixtures of mutant strains, in which the relative concentration of each
      strain was controlled. We used tag microarrays to measure the numbers of tag
      copies in each titration mixture. The data was analyzed with TagSmart and the
      result showed high precision and recall. Second, TagSmart was applied to a
      dataset in which heterozygous deletion strain mixture pools were treated with a
      new drug, Cincreasin. TagSmart identified 53 mutant strains as sensitive to
      Cincreasin treatment. We individually tested each identified mutant, and found 52
      out of the 53 predicted mutants were indeed sensitive to Cincreasin. CONCLUSION:
      TagSmart is provided "as is" to analyze tag array data produced by Affymetrix and
      Agilent arrays. TagSmart web application is assessable by Windows, Mac, and Linux
      users. It also has a downloadable version for execution on PCs running Windows.
      TagSmart is available for academic use at:
      http://biocomp.bioen.uiuc.edu/tagsmart.

PMID- 17442116
TI  - Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro
      models of colon cancer.
AB  - BACKGROUND: There is a probable association between consumption of fruit and
      vegetables and reduced risk of cancer, particularly cancer of the digestive
      tract. This anti-cancer activity has been attributed in part to anti-oxidants
      present in these foods. Raspberries in particular are a rich source of the anti
      oxidant compounds, such as polyphenols, anthocyanins and ellagitannins. METHODS:
      A "colon-available" raspberry extract (CARE) was prepared that contained
      phytochemicals surviving a digestion procedure that mimicked the physiochemical
      conditions of the upper gastrointestinal tract. The polyphenolic-rich extract was
      assessed for anti-cancer properties in a series of in vitro systems that model
      important stages of colon carcinogenesis, initiation, promotion and invasion.
      RESULTS: The phytochemical composition of CARE was monitored using liquid
      chromatography mass spectrometry. The colon-available raspberry extract was
      reduced in anthocyanins and ellagitannins compared to the original raspberry
      juice but enriched in other polyphenols and polyphenol breakdown products that
      were more stable to gastrointestinal digestion. Initiation--CARE caused
      significant protective effects against DNA damage induced by hydrogen peroxide in
      HT29 colon cancer cells measured using single cell microgelelectrophoresis.
      Promotion--CARE significantly decreased the population of HT29 cells in the G1
      phase of the cell cycle, effectively reducing the number of cells entering the
      cell cycle. However, CARE had no effect on epithelial integrity (barrier
      function) assessed by recording the trans-epithelial resistance (TER) of CACO-2
      cell monolayers. Invasion--CARE caused significant inhibition of HT115 colon
      cancer cell invasion using the matrigel invasion assay. CONCLUSION: The results
      indicate that raspberry phytochemicals likely to reach the colon are capable of
      inhibiting several important stages in colon carcinogenesis in vitro.

PMID- 17442118
TI  - Quality of chronic disease care in general practice: the development and
      validation of a provider interview tool.
AB  - BACKGROUND: This article describes the development and psychometric evaluation of
      an interview instrument to assess provider-reported quality of general practice
      care for patients with diabetes, cardiovascular disease and asthma--the
      Australian General Practice Clinical Care Interview (GPCCI). METHODS: We
      administered the GPCCI to 28 general practitioners (family physicians) in 10
      general practices. We conducted an item analysis and assessed the internal
      consistency of the instrument. We next assessed the quality of care recorded in
      the medical records of 462 of the general practitioners' patients with Type 2
      diabetes, ischaemic heart disease/hypertension and/or moderate to severe asthma.
      This was then compared with results of the GPCCI for each general practice.
      RESULTS: Good internal consistency was found for the overall GPCCI (Cronbach's
      alpha = 0.75). As far as the separate sub-scales were concerned, diabetes had
      good internal consistency (0.76) but the internal consistency of the heart
      disease and asthma subscales was not strong (0.49 and 0.16 respectively). There
      was high inter-rater reliability of the adjusted scores of data extracted from
      patients' medical notes for each of the three conditions. Correlations of the
      overall GPCCI and patients' medical notes audit, combined across the three
      conditions and aggregated to practice level, showed that a strong relationship (r
      = 0.84, p = 0.003) existed between the two indices of clinical care. CONCLUSION:
      This study suggests that the GPCCI has good internal consistency and concurrent
      validity with patients' medical records in Australian general practice and
      warrants further evaluation of its properties, validity and utility.

PMID- 17442119
TI  - Effectiveness of calf muscle stretching for the short-term treatment of plantar
      heel pain: a randomised trial.
AB  - BACKGROUND: Plantar heel pain is one of the most common musculoskeletal disorders
      of the foot and ankle. Treatment of the condition is usually conservative,
      however the effectiveness of many treatments frequently used in clinical
      practice, including stretching, has not been established. We performed a
      participant-blinded randomised trial to assess the effectiveness of calf muscle
      stretching, a commonly used short-term treatment for plantar heel pain. METHODS:
      Ninety-two participants with plantar heel pain were recruited from the general
      public between April and June 2005. Participants were randomly allocated to an
      intervention group that were prescribed calf muscle stretches and sham ultrasound
      (n = 46) or a control group who received sham ultrasound alone (n = 46). The
      intervention period was two weeks. No participants were lost to follow-up.
      Primary outcome measures were 'first-step' pain (measured on a 100 mm Visual
      Analogue Scale) and the Foot Health Status Questionnaire domains of foot pain,
      foot function and general foot health. RESULTS: Both treatment groups improved
      over the two week period of follow-up but there were no statistically significant
      differences in improvement between groups for any of the measured outcomes. For
      example, the mean improvement for 'first-step' pain (0-100 mm) was -19.8 mm in
      the stretching group and -13.2 mm in the control group (adjusted mean difference
      between groups -7.9 mm; 95% CI -18.3 to 2.6). For foot function (0-100 scale),
      the stretching group improved 16.2 points and the control group improved 8.3
      points (adjusted mean difference between groups 7.3; 95% CI -0.1 to 14.8). Ten
      participants in the stretching group experienced an adverse event, however most
      events were mild to moderate and short-lived. CONCLUSION: When used for the short
      term treatment of plantar heel pain, a two-week stretching program provides no
      statistically significant benefit in 'first-step' pain, foot pain, foot function
      or general foot health compared to not stretching.

PMID- 17442120
TI  - Aberrant over-expression of a forkhead family member, FOXO1A, in a brain tumor
      cell line.
AB  - BACKGROUND: The mammalian FOXO (forkhead box, O subclass) proteins are a family
      of pleiotropic transcription factors involved in the regulation of a broad range
      of cellular processes critical for survival. Despite the essential and diverse
      roles of the FOXO family members in human cells and their involvement in tumor
      pathogenesis, the regulation of FOXO expression remains poorly understood. We
      have addressed the mechanisms underlying the high level of expression of the
      FOXO1A gene in a cell line, PER-453, derived from a primitive neuroectodermal
      tumor of the central nervous system (CNS-PNET). METHODS: The status of the FOXO1A
      locus in the PER-453 CNS-PNET cell line was investigated by Southern blotting and
      DNA sequence analysis of the proximal promoter, 5'-UTR, open reading frame and 3'
      UTR. FOXO1A expression was assessed by conventional and quantitative RT-PCR,
      Northern and Western blotting. RESULTS: Quantitative real-time RT-PCR (qRT-PCR)
      data indicated that after normalization to ACTB mRNA levels, canonical FOXO1A
      mRNA expression in the PER-453 cell line was 124-fold higher than the average
      level of five other CNS-PNET cell lines tested, 24-fold higher than the level in
      whole fetal brain, and 3.5-fold higher than the level in fetal brain germinal
      matrix cells. No mutations within the FOXO1A open reading frame or gross
      rearrangements of the FOXO1A locus were detected. However, a single nucleotide
      change within the proximal promoter and several nucleotide changes within the 3'
      UTR were identified. In addition, two novel FOXO1A transcripts were isolated that
      differ from the canonical transcript by alternative splicing within the 3'-UTR.
      CONCLUSION: The CNS-PNET cell line, PER-453, expresses FOXO1A at very high levels
      relative to most normal and cancer cells from a broad range of tissues. The
      FOXO1A open reading frame is wild type in the PER-453 cell line and the
      abnormally high FOXO1A mRNA expression is not due to mutations affecting the 5'
      UTR or proximal promoter. Over expression of FOXO1A may be the result of PER-453
      specific epimutations or imbalances in regulatory factors acting at the promoter
      and/or 3'-UTR.

PMID- 17442121
TI  - A participatory intervention to improve the mental health of widows of injecting
      drug users in north-east India as a strategy for HIV prevention.
AB  - BACKGROUND: Manipur and Nagaland, in the north-east of India, are classified as
      high prevalence states for HIV, and intravenous drug use is an important route of
      transmission. Most injecting drug users (IDUs) are men, an estimated 40% are
      married, and death rates have been high in the last five years, consequently the
      number of widows of IDUs has increased. Many of these widows and their children
      are HIV-infected and experience poor health, discrimination, and impoverishment;
      all factors likely to be compromising their mental health. People with poor
      mental health are more likely to engage in HIV risk behaviours. Mental health can
      be promoted by public health actions with vulnerable population groups. METHODS:
      We designed an intervention study to assess the feasibility and impact of a
      participatory action process to promote the mental health and well-being of
      widows of IDUs in Manipur and Nagaland, as a strategy for reducing the risk of
      engagement in HIV risk behaviours. This paper describes the background and
      rationale for the study, the intervention, and the study methods in detail.
      RESULTS: Pending analysis. CONCLUSION: This intervention study will make a
      significant contribution to the emerging evidence that supports associations
      between mental health and HIV. The concept of promoting mental health among women
      who are vulnerable to HIV infection or already infected as a strategy for HIV
      prevention in a development setting is breaking new ground.

PMID- 17442122
TI  - Effect of peppermint water on prevention of nipple cracks in lactating
      primiparous women: a randomized controlled trial.
AB  - BACKGROUND: Nipple pain and damage in breastfeeding mothers are common causes of
      premature breastfeeding cessation. Peppermint water is popularly used for the
      prevention of nipple cracks in the North West of Iran. The aim of this study was
      to determine the effectiveness of peppermint water in the prevention of nipple
      cracks during breastfeeding in comparison with the application of expressed
      breast milk (EBM). METHODS: One hundred and ninety-six primiparous breastfeeding
      women who gave birth between February and May 2005 in a teaching hospital in
      Tabriz, Iran, were randomized to receive either peppermint water or EBM. Each
      woman was followed for up to three visits or telephone calls within 14 days and
      then by telephone call at week six postpartum. RESULTS: Women who were randomized
      to receive peppermint water were less likely to experience nipple and areola
      cracks (9%) compared to women using EBM (27%; p < 0.01). Women who used the
      peppermint water on a daily basis were less likely to have a cracked nipple than
      women who did not use peppermint water (relative risk 3.6, 95%CI: 2.9, 4.3).
      Nipple pain in the peppermint water group was lower than the expressed breast
      milk group (OR 5.6, 95% CI: 2.2, 14.6; p < 0.005). CONCLUSION: This study
      suggests that peppermint water is effective in the prevention of nipple pain and
      damage. Further studies are needed to assess the usefulness of peppermint water
      in conjunction with correct breastfeeding techniques.

PMID- 17442123
TI  - Quality in general practice consultations; a qualitative study of the views of
      patients living in an area of high socio-economic deprivation in Scotland.
AB  - BACKGROUND: Inequality in health and health care services is an important policy
      issue internationally as well as in the UK, and is closely linked to socio
      economic deprivation, which in Scotland is concentrated in and around Glasgow.
      Patients views on primary care in deprived areas are not well documented. In the
      present study we explore the views of patients living in a high deprivation area
      on the quality of consultations in general practice. METHODS: Qualitative focus
      group study set in an area of high socio-economic deprivation in a large
      peripheral housing estate in Glasgow, Scotland. 11 focus groups were conducted; 8
      with local community groups and 3 with other local residents. In total 72
      patients took part. Grounded theory was used to analyse the data. RESULTS:
      Patients' perceptions of the quality of the consultation with GPs consisted of
      two broad, inter-relating themes; (1) the GPs' competence, and (2) the GPs
      empathy or ' caring'. Competence was often assumed but many factors coloured this
      assumption, in particular whether patients had experienced (directly or
      indirectly with a close family member) 'successful' outcomes with that doctor
      previously or not. 'Caring' related to patients feeling (a) listened to by the
      doctor and being able to talk; (b) valued as an individual by the doctor (c) that
      the doctor understood 'the bigger picture', and (d) the doctors' explanations
      were clear and understandable. Relational continuity of care (being able to see
      the same GP and having a good relationship), and having sufficient time in the
      consultation were closely linked with perceptions of consultation quality.
      CONCLUSION: Patients from deprived areas want holistic GPs who understand the
      realities of life in such areas and whom they can trust as both competent and
      genuinely caring. Without this, they may judge doctors as socially distant and
      emotionally detached. Relational continuity, empathy and sufficient time in
      consultations are key factors in achieving this.

PMID- 17442124
TI  - Quality of care: assessment.
AB  - To translate science into clinical practice we must first assess the quality of
      care that is being delivered. The resulting information about qualitative and
      quantitative parameters can then be assessed. Ultimately insights can be obtained
      into improving the quality of care in diabetes mellitus. The Diabetes Quality
      Improvement Programme in USA has shown such an exercise is feasible. A similar
      exercise in India is necessary to improve the quality of diabetes care.

PMID- 17442125
TI  - Internet-based treatment for PTSD reduces distress and facilitates the
      development of a strong therapeutic alliance: a randomized controlled clinical
      trial.
AB  - BACKGROUND: The present study was designed to evaluate the efficacy of an
      internet-based therapy (Interapy) for Posttraumatic Stress Disorder (PTSD) in a
      German speaking population. Also, the quality of the online therapeutic
      relationship, its development and its relevance as potential moderator of the
      treatment effects was investigated. METHOD: Ninety-six patients with
      posttraumatic stress reactions were allocated at random to ten sessions of
      Internet-based cognitive behavioural therapy (CBT) conducted over a 5-week period
      or a waiting list control group. Severity of PTSD was the primary outcome.
      Secondary outcome variables were depression, anxiety, dissociation and physical
      health. Follow-up assessments were conducted at the end of treatment and 3 months
      after treatment. RESULTS: From baseline to post-treatment assessment, PTSD
      severity and other psychopathological symptoms were significantly improved for
      the treatment group (intent-to-treat group x time interaction effect size d =
      1.40). Additionally, patients of the treatment condition showed significantly
      greater reduction of co-morbid depression and anxiety as compared to the waiting
      list condition. These effects were sustained during the 3-months follow-up
      period. High ratings of the therapeutic alliance and low drop-out rates indicated
      that a positive and stable therapeutic relationship could be established online.
      Significant improvement of the online working alliance in the course of treatment
      and a substantial correlation between the quality of the online relationship at
      the end of treatment and treatment outcome emerged. CONCLUSION: Interapy proved
      to be a viable treatment alternative for PTSD with large effect sizes and
      sustained treatment effects. A stable and positive online therapeutic
      relationship can be established through the Internet which improved during the
      treatment process. TRIAL REGISTRATION: Australian Clinical Trials Registry
      ACTRN012606000401550.

PMID- 17442126
TI  - What does high NT-proBNP mean in septic shock patients? A part of the puzzle.
AB  - B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) plasma
      levels are commonly high at the early phase of septic shock and have been
      suggested to be prognostic markers for this condition. It is uncertain, however,
      whether this increase reflects sepsis related cardiac dysfunction. In a recent
      issue of Critical Care, Mokart and coworkers showed the accuracy of NT-proBNP in
      predicting intensive care unit mortality in cancer patients with septic shock,
      which could help in identifying high risk cancer patients. Results from repeated
      transthoracic echocardiographs show that NT-proBNP on day 2 after admission was
      higher in patients presenting with cardiac dysfunction, whereas NT-proBNP on day
      1 did not predict cardiac dysfunction. These data suggest that after an initial
      overexpression of NT-proBNP in all septic patients, patients with cardiac
      dysfunction will present persistent high levels of NT-proBNP.

PMID- 17442127
TI  - Pro/con debate: in patients who are potential candidates for organ donation after
      cardiac death, starting medications and/or interventions for the sole purpose of
      making the organs more viable is an acceptable practice.
AB  - Several hospitals have been developing programmes for organ donation after
      cardiac death. Such programmes offer options for organ donation to patients who
      do not meet brain-death criteria but wish to donate their organs after withdrawal
      of life-support. These programmes also increase the available organ pool at a
      time when demand exceeds supply. Given that potential donors are managed in
      intensive care units, intensivists will be key components of these programmes.
      Donation after cardiac death clearly carries a number of important ethical issues
      with it. In the present issue of Critical Care two established groups debate the
      ethical acceptability of using medications/interventions in potential organ
      donors for the sole purpose of making the organs more viable. Such debates will
      be an increasingly common component of intensivists' future practice.

PMID- 17442128
TI  - Exploring genomes in agriculture and food science.

PMID- 17442129
TI  - Prenatal exposure to undernutrition and programming of responses to high-fat
      feeding in the rat.
AB  - Fetal undernutrition programmes risk of later metabolic disorders. Postnatal
      factors modify the programmed phenotype. This study aimed to assess the effects
      of a postnatal high-fat (HF) challenge on body weight gain, adiposity and gene
      expression following prenatal undernutrition. Pregnant rats were fed either a
      control diet or a low-protein (LP) diet, targeted at days 0-7 (LPE), days 8-14
      (LPM), or days 15-22 (LPL) gestation. At 12 weeks of age offspring were either
      fed standard laboratory chow diet (4.13 % fat), or a 39.5 % fat diet, for 10
      weeks. LP exposure had no effect on weight gain or abdominal fat in males.
      Females exposed to LP diet in utero exhibited a similar weight gain on HF diet as
      on the chow diet. Programming of fat deposition was noted in LPE females and
      males of the LPM and LPL groups (P = 0.019). Hypothalamic expression of galanin
      mRNA was similar in all groups, but expression of the galanin-2 receptor was
      modified by LP exposure in female offspring. Hepatic expression of sterol
      response element binding protein (SREBP-1c) was decreased by LP at both the mRNA
      (P = 0.008) and protein (P < 0.001) level. HF feeding increased expression of
      SREBP-1c mRNA three-fold in controls, with little response noted in the LP
      groups. Interactions of factors such as postnatal diet, age and sex act together
      with prenatal factors to determine metabolic function and responsiveness at any
      stage of postnatal life. This study further establishes a role for prenatal
      nutrition in programming the genes involved in lipid metabolism and appetite
      regulation.

PMID- 17442130
TI  - Nutritional status and subsequent all-cause mortality in men and women aged 75
      years or over living in the community.
AB  - We prospectively investigated relationships between blood markers of Fe, vitamin
      B12, folate, vitamin C and vitamin D status and subsequent all-cause mortality in
      208 men and 191 women aged 75 years or over living in the community in Aberdeen,
      Scotland. The participants had been recruited for a cross-sectional study in 1999
      2000 when they completed health and lifestyle questionnaires and had blood
      samples taken for analysis of serum ferritin, serum vitamin B12, erythrocyte
      folate, plasma vitamin C and serum 25-hydroxycholecalciferol. Mortality was
      ascertained on national databases up to December 2005, with a median time of
      follow up of 69.2 (range 1.0-79.9) months. Participants were divided into sex
      specific quintiles of baseline levels for each nutrient, and hazard ratios were
      estimated with Cox proportional hazard models adjusted for age and sex with the
      significance of linear trends in the associations assessed by logistic
      regression. There was no significant association between blood markers of Fe,
      vitamin B12 or folate status at baseline and mortality, but vitamin D status at
      baseline was inversely related to mortality (P for trend < 0.001). For vitamin C
      there was no evidence of a linear trend but participants in the lowest quintile
      of plasma levels had a significantly higher risk of death than those in the
      highest quintile. Randomized controlled trials of lifestyle changes which improve
      vitamin status are needed to assess whether these associations could be causal.

PMID- 17442131
TI  - Carbachol induces hepatocyte proliferation, but only in the presence of hepatic
      nonparenchymal cells.
AB  - Vagal hyperactivity correlates with enhanced DNA synthesis and cell proliferation
      in the peripheral tissues of ventromedial hypothalamic (VMH)-lesioned rats. The
      infusion of an ACh receptor agonist, carbachol (Cch), induces rat duodenal and
      pancreatic cell proliferation to a degree comparable to the VMH lesions. Whereas
      the VMH lesions also induce the proliferation of hepatic cells, it is unclear
      whether Cch can also do this. Here we attempted to clarify the mechanism of
      hepatic cell proliferation induction by cholinergic stimulation. First, hepatic
      cell proliferation was examined in rats previously vagotomized and
      intraperitoneally administered with Cch via an osmotic minipump. Second, the sera
      from the Cch-infused rats were examined for a proliferative effect on isolated
      hepatic cells. And last, the effect of the presence of hepatic nonparenchymal
      cells (NPCs) on the proliferation of the cultured hepatocytes treated with Cch
      was investigated. Immunohistochemistry for proliferating cell nuclear antigen
      (PCNA) showed that the 3-day Cch infusion significantly increased the number of
      PCNA-immunoreactive cells in the liver. Moreover, the sera from the Cch-infused
      rats increased the number of PCNA-immunoreactive hepatocytes in culture. However,
      Cch alone did not induce proliferation in monocultured hepatocytes. When compared
      with the monoculture of hepatocytes, the coculture of those with hepatic NPCs
      resulted in enhanced PCNA immunoreactivity after a 4-day treatment with 3 mM Cch.
      These findings suggest that ACh induces hepatocyte proliferation, which is
      mediated by unidentified humoral factor(s) possibly secreted from hepatic NPCs,
      and that it also participates in liver hypertrophy in the VMH-lesioned animals.

PMID- 17442132
TI  - Who will provide secondary care in rural Canada?

PMID- 17442133
TI  - President's message. Another year...

PMID- 17442134
TI  - Different practice patterns of rural and urban general practitioners are
      predicted by the General Practice Rurality Index.
AB  - INTRODUCTION: There are differences between rural and urban general medical
      practice. However, research in this area has been hampered by the lack of a
      practical and valid definition of "rural." This study attempts to validate the
      General Practice Rurality Index (GPRI) by showing that it can predict the fee-for
      service billing patterns of general practitioners in British Columbia. METHODS:
      We obtained one year of fee-for-service billing data for all general
      practitioners in BC, apportioned by local health area (LHA). The total numbers of
      each type of service in each LHA were categorized into logical groups and
      expressed as a percentage of total services for that LHA. Each LHA was given a
      full GPRI score and a simplified GPRI (GPRI-S) score. We then compared the scores
      and percentage of services in each fee category. RESULTS: We found significant
      correlations between the degree of rurality and the percentage of certain
      services. The GPRI-S produced more significant correlations than the full GPRI.
      CONCLUSIONS: This study provides evidence that both the full GPRI and a
      simplified version can be used to predict practice patterns of BC general
      practitioners. Further study is needed to prove whether either of these indices
      will be an accurate and reliable measure of rurality across Canada.

PMID- 17442135
TI  - Bridging the gap in population health for rural and Aboriginal communities: a
      needs assessment of public health training for rural primary care physicians.
AB  - INTRODUCTION: The literature identifies significant inequalities in the health
      status of rural and Aboriginal populations, compared with the general population.
      Providing rural primary care physicians with public health skills could help
      address this issue since the patterns of mortality and morbidity suggest that
      prevention and health promotion play an important role. However, we were unable
      to identify any community needs assessment for such professionals with dual
      skills that had been performed in Canada. METHODS: We conducted key informant
      interviews and focus groups in 3 rural and Aboriginal communities in British
      Columbia (chosen through purposive sampling). We analyzed transcripts following
      standard qualitative iterative methodologies to extract themes and for discussing
      content. RESULTS: There was broad support for a program to train primary care
      physicians in public health. The characteristics identified as necessary in such
      a physician included a long-term commitment to the community with partnership
      building, advocacy, communication and cultural sensitivity skills. The
      communities we studied identified some priority challenges, most notably that the
      current remuneration structure does not support physicians engaging in public
      health or research. CONCLUSION: There is great potential and support for the
      training of rural primary care practitioners in public health to improve
      population health and engage communities in this process.

PMID- 17442136
TI  - Rural maternity care services under stress: the experiences of providers.
AB  - INTRODUCTION: Between 2000 and 2004, 17 small rural maternity care services in
      British Columbia (BC) closed or were placed under moratoria. This paper explores
      the experiences of care providers in 4 rural BC communities that have lost or are
      at risk of losing their local maternity services. METHODS: We conducted
      qualitative, semistructured interviews and focus groups with 27 health care
      providers (doctors and nurses) and 3 administrators. The analysis used modified
      grounded theory. We chose 4 rural communities to include a diversity of
      characteristics, including community size, geography, distance to the nearest
      hospital capable of performing cesarean section, and cultural and ethnic
      subpopulations. RESULTS: Care providers identified significant stressors related
      to the provision of maternity care services, including the development and
      maintenance of competency in the context of decreasing birth volume, the safety
      of local maternity care without cesarean section and the desire to balance
      women's needs with the realities of rural practice. CONCLUSIONS: Maternity care
      providers in small rural communities are experiencing stress due in part to the
      absence of evidence-based policy and planning for rural maternity care services.
      This stress may contribute to challenges in the retention of rural maternity care
      providers, thus risking the future of small rural maternity services.

PMID- 17442137
TI  - Myocardial infarction in Quebec rural and urban populations between 1995 and
      1997.
AB  - INTRODUCTION: There is abundant evidence of health inequities between urban and
      rural populations. The purpose of this paper is to describe the socioeconomic
      characteristics of Quebec urban and rural populations and the relation between
      rurality and incidence of myocardial infarction (MI), care management and
      outcomes. METHODS: Socioeconomic data by census subdivisions were available from
      the 1996 Canadian census, representing 7,137,245 individuals. Data on patients
      with MI were taken from the provincial administrative health database (MED-ECHO),
      which is managed by the Ministry of Health and contains clinical and demographic
      information collected when patients are released from acute care hospitals in
      Quebec. RESULTS: We included a total of 37,678 cases compiled over the 3 years of
      follow-up in the analyses. Residents of rural areas with low urban influence have
      higher MI incidence rates than all of the other populations in the study. In
      comparison with urban populations, their observed rural counterparts are at a
      disadvantage with regard to education, employment and income. Although
      angioplasty and coronary artery bypass graft surgery rates were higher in more
      urban areas, the survival rate was lower than in rural areas. CONCLUSION: This
      study revealed geographic heterogeneity of MI incidence, revascularization rates
      and survival rates among urban and rural populations.

PMID- 17442138
TI  - The occasional shoulder reduction.

PMID- 17442139
TI  - Microsoft Vista: who needs it?

PMID- 17442151
TI  - [To upgrade the academic quality by insisting on the correct direction].

PMID- 17442152
TI  - [Advance together for common future].

PMID- 17442153
TI  - [Current status and recommendation of ocular surface disease in China].
AB  - Basic research on ocular surface disease is currently focused on the location,
      marker and culture of corneal limbal stem cells, the biological character and
      function of amniotic membrane; the culture carriers for stem cells and goblet
      cells are also addressed. But many of the investigations are lack of scientific
      originality in the international community. A lot of efforts have been put in
      clinical research, especially in ocular surface reconstruction, which has been
      widely applied and has yielded satisfactory surgical results. However, a set of
      integrated surgical rules is essential to make scientific criteria for the extent
      of ocular surface impairment and treatment efficacy. Moreover, indications for
      use of amniotic membrane are in random expansion in some degree, and there is no
      regulation for obtaining amniotic materials. In addition, diagnosis and treatment
      of dry eye symptom remains in the status of austerity. Suggestions are made
      regarding the existing problems.

PMID- 17442154
TI  - [Aware of glaucoma in the patients after excimer laser refractive surgery].
AB  - The prevalence of glaucoma in myopic patients is about two to three times than in
      general population, in which the prevalence of glaucoma is about 1%-2%. Millions
      of patients have been performed excimer laser refractive surgery for their
      refractive error. Thus, tens of thousands of the patients who received the
      refractive surgery will suffer from glaucoma in the next two decades. Some
      studies have found intraocular pressure (IOP) in patients with refractive surgery
      is lower, most likely due to the reduced central corneal thickness and
      intralamellar cyst syndrome. The use of steroid after the refractive surgery can
      increase IOP in the steroid responders. Therefore, the refractive surgeons should
      pay more attention to patient follow-up and surveillance of IOP.

PMID- 17442155
TI  - [Clinical observation of dry eye in patients before and after cataract surgery].
AB  - OBJECTIVE: To investigate dry eye in patients before and after cataract surgery.
      METHODS: 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ25)
      and Ocular Surface Disease Index (OSDI) were used for the study in 37 patients
      (50 eyes) 3 days before cataract surgery and repeated after surgery 1 week, 1
      month and 3 months. Slit lamp microscope examination, cornea and conjunctiva
      fluorescein staining, tear break-up time (BUT), Schirmer test I (STI), impression
      cytology (IC) were carried out at the same time. RESULTS: After cataract surgery,
      the incidence of dry eye increased dramatically. Tear river was narrowed, BUT and
      STI were decreased and shorted in patients after cataract surgery. IC examination
      showed there was serious squamous metaplasia in epithelial layer of conjunctiva.
      NEI-VFQ25 was increased from 27.66 +/- 22.08 (before cataract surgery) to 74.69
      +/- 11.67 (3 months after cataract surgery). All items of OSDI were remarkable
      increased, ocular surface abnormal was increased from 2.60 +/- 2.91 (before
      cataract surgery) to 12.66 +/- 11.40 (3 months after cataract surgery) and
      environmental trigger was increased from 3.57 +/- 2.67 (before cataract surgery)
      to 11.40 +/- 10.24 (3 months after cataract surgery). CONCLUSION: Dry eye can be
      induced or deteriorated after cataract surgery, if it can not be treated on time.

PMID- 17442156
TI  - [Preliminary report of surgical treatment of vernal keratoconjunctivitis with
      giant papillae].
AB  - OBJECTIVE: To evaluate the efficacy and safety of excision and cryotherapy
      combine with amniotic membrane transplantation (AMT) for the treatment of vernal
      keratoconjunctivitis (VKC) with giant papillae (GP). METHODS: Eight patients (16
      eyes) with VKC, characterized by GP on the upper tarsal conjunctiva, refractory
      to medical treatment, underwent excision and cryotherapy associated with AMT. The
      follow up period ranged 3-22 months. RESULTS: Corneal shield ulcers and
      superficial punctuate keratitis healed during the first week after the surgery
      and did not recur. Fourteen eyes were symptom free and without GP one month after
      surgery. No ectropion, trichiasis and other complications were noted. The blood
      vessels of upper tarsal conjunctiva could not be seen clearly, a small amount of
      conjunctival scar was observed. Recurrence of GP was observed in 2 eyes, with
      reduced area and lessened irritation symptom as compared with preoperative
      status. Among them, one eye was treated by cyclosporine eyedrops with
      improvement. The other eye did not improve, and underwent secondary surgery (a
      cotton patch soaked in fluorouracil was applied on the upper eyelid after
      excision and cryotherapy). Nine months after the treatment, the patient had no
      symptoms and GP did not recur. CONCLUSIONS: Excision and cryotherapy combine with
      AMT may be an effective and safe method for the treatment of refractory VKC with
      GP. But the candidates for surgical treatment should be chosen carefully.

PMID- 17442157
TI  - [Expression of apoptosis related genes and changes of lacrimal functions in main
      lacrimal gland extirpation xerophthalmia model].
AB  - OBJECTIVE: To establish a main lacrimal gland extirpation xerophthalmia model and
      to study the relationship between expression of apoptosis genes in various ocular
      surface cells (cornea and conjunctiva epithelium cells and Meibomian cells) and
      ocular surface sicca as well as tissue damages in this model. METHODS: Twenty
      adult Wistar rats were included in this study and allocated to two groups
      randomly. Main lacrimal glands were excised in 10 animals and Schirmer I test,
      tear film break-up time (BUT) and fluorescence staining were performed before the
      operation and 3 days, 1, 2, 4, 8 and 12 weeks after the operation. Ten
      experimental animals and ten normal animals in the control group were
      investigated by immunohistochemistry staining of the cornea, conjunctivas
      epithelium cells and Meibomian cells to detect the expression of Bax and Bcl-2
      gene. RESULTS: Schirmer I test and BUT were significantly lower in the
      experimental group 1-2 weeks after the operation. The difference became more
      prominent in the course of observation (P < 0.05). Fluorescence staining was
      positive in the experimental group. Cornea, conjunctival epithelial cells and
      Meibomian cells showed more increased expression of Bax in the experimental group
      [(503.47 +/- 343.73), (586.36 +/- 296.47), (436.61 +/- 246.96) every thousands
      cells] than that in the normal controls [(241.71 +/- 130.12), (311.03 +/-
      142.33), (202.16 +/- 109.29) every thousands cells] (P < 0.05). Bcl-2 expression
      was decreased in the experimental group [(237.32 +/- 87.07), (236.07 +/- 81.24),
      (251.79 +/- 89.93) every thousands cells] as compared to the normal controls
      [(474.24 +/- 167.62), (342.81 +/- 114.57), (320.42 +/- 153.32) every thousands
      cells] (P < 0.05). CONCLUSIONS: The apoptosis of the epithelial cells in cornea,
      conjunctiva and Meibomian cells may be one of the mechanisms lead to the
      destruction of ocular surface tissues in xerophthalmia.

PMID- 17442158
TI  - [Hypertonic saline-assisted laser-assisted subepithelial keratectomy for the
      correction of moderate and low myopia].
AB  - OBJECTIVE: To evaluate the effectiveness of hypertonic saline (5% sodium
      chloride) in execution of epithelial flap in laser-assisted subepithelial
      keratomileusis (HS-LASEK) for treatment of moderate and low myopia. METHODS: 48
      patients (96 eyes) with moderate and low myopia were divided into 2 groups. In
      Group A (A-LASEK, 22 patients 44 eyes), 20% alcohol was used to create the
      epithelial flap; in Group B (HS-LASEK, 26 patients 52 eyes), 5% sodium chloride
      was used to create the epithelial flap. Postoperative visual acuity, refraction
      power, time of epithelial healing, and haze were recorded. The patients were
      followed-up for 6 months. RESULTS: The mean time of epithelial healing was (4.52
      +/- 0.21) days in A-LASEK eyes, while (3.84 +/- 0.39) days in HS-LASEK eyes, the
      difference of epithelial healing time between the two groups was statistically
      significant. Visual acuity in all patients were improved by the surgery, 3 days
      after operation, visual acuity reached 0.8 or better in 27.3% (12/44) of A-LASEK
      eyes and 48.1% (25/52) of HS-LASEK eyes, the difference between the two groups
      was statistically significant (P < 0.05). Two weeks after operation corneal haze
      was found in 13 eyes (29.5%) of A-LASEK group and 15 eyes (28.8%) of HS-LASEK
      group, but the grade haze was below 0.5 and had no effect on visual acuity, after
      3 months, haze was noted in 10% of eyes in each groups, the difference of corneal
      haze between the two groups was no statistically significant (P > 0.05). One day
      after operation 12 eyes (27.3%) of A-LASEK and 6 eyes (11.5%) of HS-LASEK had
      obvious pain, the difference between the two groups was statistically significant
      (P < 0.05). CONCLUSION: HS-LASEK is a safe surgery for the correction of moderate
      and low myopia as A-LASEK, and have a better curative effect than A-LASEK.

PMID- 17442159
TI  - [The clinical features and surgical treatment of masked bilateral superior
      oblique palsy].
AB  - OBJECTIVE: To investigate the clinical features, diagnosis and the management of
      masked bilateral superior oblique palsy (MBSOP). METHODS: Retrospectively
      analyzed the records of all 7 patients that met the clinical criteria for MBSOP
      in Zhongshan Ophthalmic Center between 1999 and 2003. The head tilt, vertical
      deviation in primary position and the action of obliquus pre- and postoperatively
      were collected in detail. RESULTS: All 7 patients were diagnosed as unilateral
      SOP in the first time. The average hypertropia in primary position preoperatively
      was 19.7(Delta) (range 6(Delta) to 30(Delta)). All patients had a head tilt,
      obvious unilateral inferior oblique overaction (+2 to +4) and mild superior
      oblique underaction (-1 to -2), and normal action in contralateral superior and
      inferior obliquus. Initial surgery consisted of ipsilateral inferior oblique
      weakening with (5 patients) or without (2 patients) ipsilateral superior rectus
      recession. The average hypertropia in primary position was 12.0(Delta) (range
      0(Delta) to 20(Delta)) after the first operation. In 1 week to 4 years, all of
      the previously masked eye presented the inferior oblique overaction (+2 to +3)
      and superior oblique underaction (0 to -1). All patients underwent a second
      surgery in 4 months to 4 years after the initial surgery. The average hypertropia
      in primary position was 2.3(Delta) (range 0(Delta) to 7(Delta)) after the second
      operation. Postoperative alignment was excellent in all patients. CONCLUSIONS:
      Masked bilateral superior oblique palsy is quite difficult to detect before
      surgical correction of the initial manifest palsy. The possibility of an occult
      contralateral palsy should be considered in all undergoing surgery for unilateral
      SOP. The superior rectus recession and the inferior oblique weakening procedure
      should be performed at different stages. When the masked palsy becomes evident, a
      successful surgical outcome can usually be expected.

PMID- 17442160
TI  - [The clinical and pathogenic characteristics of keratitis caused by Alternaria
      alternata].
AB  - OBJECTIVE: To study the clinical and pathogenic characteristics of keratitis
      caused by Alternaria alternata and to provide evidence for the diagnose and
      treatment of mycotic keratitis. METHODS: The patients with keratitis were
      examined by lamp microscope; the direct smears of corneal scrapings were stained
      using 10% potassium hydroxide and Giemsa's staining and the results were observed
      under microscope. After hypha was found, the samples from corneal were taken for
      fungal culture and fungal susceptibility test in vitro according to the National
      Community of Clinical Laboratory Standard (NCCLS) document M38-A at the same
      time. Ketoconazole, Amphotericin B and Fluconazole eye drops were applied into
      eyes frequently and alternately. The affectivity of the treatment were also
      observed. The isolates of Alternaria alternata from patients were used to induce
      keratitis in rabbits. The rabbits were sacrificed by air after 5 days and 14 days
      and their corneas were taken for pathology and inoculating for fungi. RESULTS:
      All the patients have only one eye with Alternaria alternata's keratitis and
      their average age was 50 years old. The lesions of corneal necrosis in the
      patients and Alternaria alternata's keratitis in the rabbits were appeared as
      light grey, shallow and a diffused edge. Alternaria alternata showed as thick
      transparent hypha and a great of spherical chlamydospores on the top of hypha or
      cluster one and the other in corneal scraping under microscope. The hypha and
      spores of Alternaria alternata in the culture medium were all brown and the
      spores were separated into cells like wall brick and grew on the top of spores
      linking like chains. Anti-microbial susceptibility testing in vitro showed that
      Alternaria alternata was susceptible to Voriconazole, Amphotericin B,
      Ketoconazole, Miconazole, Econazole, Terbinafine and Fluconazole but it was
      resistant to Clotrimazole, Flucytosine ang Itraconazole. 22 of the patients were
      cured by dropping Amphotericin B, Ketoconazole and Fluconazole frequently and
      alternately but surgery was performed in one case. The mean cured time was 34
      day. The lesion of rabbits keratitis caused by Alternaria alternata was thin and
      localized only in the region of lacking epicytes. The isolate from the rabbit's
      keratitis model was Alternaria alternata. CONCLUSIONS: The keratitis caused by
      Alternaria alternata has its distinct clinical and laboratory characteristics.
      The virulence of Alternaria alternata is relatively low to cornea and the
      combination of anti-fungal agents could cure Alternaria alternata keratitis.

PMID- 17442161
TI  - [Imaging diagnosis of carotid-cavernous fistula].
AB  - OBJECTIVE: To evaluate the diagnostic value of ultrasound, CT and MRI in carotid
      cavernous fistula. METHODS: A retrospective analysis was made of 58 patients with
      carotid-cavernous fistula who had complete clinical data from 1997-2004. The
      imaging findings of B-ultrasound, color Doppler ultrasonography, CT and MRI were
      analyzed and summarized for the diagnosis of carotid-cavernous fistula. RESULTS:
      The imaging findings of carotid-cavernous fistula included of dilation of
      superior ophthalmic vein, enlargement of cavernous sinus, proptosis, and
      thickness of extraocular muscle. Dilation of superior ophthalmic vein was the
      specific imaging sign of carotid-cavernous fistula. This was presented in 51
      cases by B-ultrasound which showed one tubular no-echo space; presented in 49
      patients by color Doppler imaging which showed obvious dilated superior
      ophthalmic vein with artery blood flow; presented in 58 cases by CT scan which
      showed fusiform vascular imaging from anterior-inside to posterior-outside; and
      presented in 58 cases by MRI with the characteristic manifestation: flow void
      signal of dilated superior ophthalmic vein on T(1)WI and T(2)WI scan, and on the
      Gd-enhanced MRI. Another specific imaging sign was enlargement of cavernous
      sinus. This sign was presented in 41 cases by CT with high density imaging and
      presented in 37 cases by MRI, which showed flow void signal on T(1)WI and T(2)WI
      scan. CONCLUSION: Carotid-cavernous fistula has specific imaging signs which can
      be found by B-ultrasound, color Doppler ultrasonography, CT and MRI. These
      imaging signs are important to clinical diagnosis and different diagnosis of
      carotid-cavernous fistula.

PMID- 17442162
TI  - [Expression of glucocorticoid receptor alpha and beta mRNA in orbital tissues in
      thyroid associated ophthalmopathy].
AB  - OBJECTIVE: To evaluate the expression of glucocorticoid receptor alpha (GRalpha)
      and beta (GRbeta) messenger RNA (mRNA) in orbital tissues from thyroid associated
      ophthalmopathy (TAO). METHODS: Samples of extraocular muscle and orbital fat were
      obtained from 17 patients with TAO and 10 healthy individuals. Total RNA was
      extracted and reversely transcripted into cDNA. The expression of GRalpha and
      GRbeta mRNA was detected by means of fluorescent quantitative polymerase chain
      reaction (PCR). RESULTS: Expression of GRalpha mRNA was much higher than GRbeta
      mRNA in all extraocular muscle and orbital fat biopsies. The relative copy of
      GRalpha was 40.15 +/- 11.37 in TAO patients and 20.64 +/- 7.07 in the controls.
      GRalpha: GRbeta mRNA ratio of these two groups was 77.76 +/- 18.77 and 148.34 +/-
      23.86, respectively. There was significant difference between these two groups (P
      < 0.05). No significant difference was noted between extraocular muscle and
      orbital fat biopsies, between glucocorticoid-treated and non-treated patients or
      among hyperthyroidism, hypothyroidism and euthyroidism (P > 0.05). CONCLUSIONS:
      The increased expression of GRalpha mRNA and decreased GRalpha: GRbeta ratio in
      orbital tissues may play an important role in the pathogenesis of TAO and the
      effects of glucocorticoid treatment.

PMID- 17442163
TI  - [Hydrogen peroxide induces expression and transcription of erythropoietin in the
      human retinal pigment epithelium cells].
AB  - OBJECTIVE: To investigate the expression of erythropoietin (EPO) in human fetal
      retinal pigment epithelium (hfRPE) cells exposed to oxidative stress induced by
      hydrogen peroxide (H(2)O(2)) and to study the mechanisms. METHODS: The hfRPE
      cells were isolated, cultured and identified. The content of malondialdehyde
      (MDA) and the activity of superoxide dismutase (SOD) of the hfRPE cells were
      examined. The changes of level of mRNA and protein of EPO in hfRPE cells exposed
      to oxidative stress were measured by semi-quantitative RT-PCR and
      immunocytochemical staining techniques. RESULTS: H(2)O(2) could increase the
      content of MDA and inhibit the activity of SOD in hfRPE cells. RT-PCR detected a
      significant increase of EPO mRNA level in cultured hfRPE cells exposed to
      oxidative stress. The level of EPO mRNA in the hfRPE cells reached a peak when
      exposed to 600 micromol/L H(2)O(2), then decreased after exposing to 800
      micromol/L H(2)O(2). The immunocytochemical study detected that the changes of
      the level of EPO protein were similar to that of EPO mRNA. CONCLUSION: Oxidation
      stress by exposed to H(2)O(2) induces significant increase of EPO expression of
      hfRPE cells. Expression of EPO may be related to the survival and tolerance of
      hfRPE cells.

PMID- 17442164
TI  - [Modulation of expression of platelet-derived growth factor by nuclear
      transcription factor-kappaB in rats retina].
AB  - OBJECTIVE: To determine whether nuclear transcription factor-kappaB (NF-kappaB)
      could modulate the expression of platelet-derived growth factor (PDGF) in rat
      retina induced by interleukin-1beta (IL-1beta) and studied the mechanism of
      inflammation-associated retinal diseases such as intraocular inflammation and
      proliferative vitreoretinopathy (PVR). METHODS: One hundred and twenty eight
      Sprague-Dawley rats were divided into A, B, C and D groups, the right eyes were
      served as experimental eyes, and the left eyes as normal controls. Animals
      received 2 intravitreal injections at 1 hour interval, which included BSS and BSS
      (group A); BSS and IL-1beta (group B); pyrrolidine dithiocarbamate (PDTC) and BSS
      (group C); PDTC and IL-1beta (group D). PDTC was one of special inhibitors of NF
      kappaB activation. The Rat eyes were examined by slit-lamp before intravitreal
      injection, 4 and 24 hours after the injection. Degree of intraocular inflammation
      was graded using a scoring system. Rats were sacrificed 4 and 24 hours after the
      injection, the expressions of NF-kappaB and PDGF were detected by
      immunohistochemistry and reverse transcriptase polymerase chain reaction (RT
      PCR). RESULTS: Four hours after the injection, eyes in group B, as compared with
      group D, showed more severe intraocular inflammatory signs such as photophobia,
      iris hyperemia, miosis, large amount of fibrin exudates and posterior synechia of
      iris. Histopathologic examination showed numerous inflammatory cells within the
      retinal parenchyma, vitreous and ciliary body. Positive cells of NF-kappaB and
      PDGF in group D, which could be observed within inner nuclear layer and ganglion
      cell layer, were obviously less than that in group B. The expression of PDGF mRNA
      was less in group D compared with group B (P < 0.05), however the expression of
      PDGF-A mRNA was significantly higher than PDGF-B in group B and group D (P <
      0.05). Twenty four hours after the injection, intraocular inflammation alleviated
      gradually, the expression of PDGF and NF-kappaB decreased obviously. CONCLUSIONS:
      These results suggest that NF-kappaB modulates the expression of PDGF in rat
      retina induced by IL-1beta. Upregulation of PDGF may play an important role in
      the occurrence of intraocular inflammation and the different isoform of PDGF may
      have different impact on various ocular diseases.

PMID- 17442165
TI  - [Expression of liposome-mediated PEDF-GFP gene in the retina of the BN rats
      through different gene delivery route].
AB  - OBJECTIVE: Transducing PEDF-GFP plasmid to the retina of the BN rats with
      cationic liposome through different gene delivery route, then observe the
      expression and location of the PEDF-GFP. METHODS: PEDF-GFP plasmid with cationic
      liposome was delivered to the retina of the BN rat through subretinal injection
      and intravitreal injection. The expression of GFP was observed under fluorescence
      microscope, and the mRNA of PEDF gene was detected by RT-PCR. RESULTS: Green
      fluorescence was emitted from the total retina include RPE cell under fluorescent
      microscope after 24 h in two gene delivery route, The fluorescence intensity was
      stronger with time changing. Gradual fluorescence increase in the retina and RPE
      cells occurred and lasted 4 weeks. The expression of PEDF mRNA was also detected
      by RT-PCR after 24 h, and maintained stable 4 weeks after infection. CONCLUSIONS:
      Cationic liposome can mediate PEDF-GFP gene into the retina of the BN rat
      effectively; subretinal injection and intravitreal injection both are effective
      gene delivery route; and their stable expression can maintain 4 weeks after
      transfection.

PMID- 17442166
TI  - [Imaging features after radial optic neurotomy in cat eyes].
AB  - OBJECTIVE: To evaluate the imaging features of cat optic disc after radial optic
      neurotomy (RON). METHODS: A total of 10 healthy cats underwent RON unilaterally
      and examined by optical coherence tomography (OCT) and fundus fluorescein
      angiography (FFA) 1, 15, 30 and 90 days after the operation. RESULTS: One day
      after the operation, OCT showed that the depth of the incision reached the lamina
      cribrosa, with edema and thickening of the surrounding sensory retina. On the
      15th day, the sensory retina edema and thickening were disappeared. On the 30th
      day, the depth of incision became shallow. Ninety days after the operation, the
      scar protruded from the lamina cribrosa. FFA examination showed that the incision
      appeared as hypofluorescence strip one day after the operation with retinal
      vessels leakage near the incision at vein phase. Incision was enlarged 15 to 30
      days later, with hypofluorescence at early phase and partial staining at late
      phase. Ninety days after the operation, there was hypofluorescence at early phase
      and obvious scar staining at late phase. CONCLUSION: The imaging features of RON
      conform to a reparative process.

PMID- 17442173
TI  - [Current status of researches on ocular surface related mucins].
AB  - Mucins comprise a family of highly glycosylated, high-molecular-weight
      glycoproteins. Ocular surface mucins are the major component of the tear film.
      They play important role in maintaining the ocular surface health. The
      alterations in the structure and expression pattern of mucins are related to the
      pathophysiology process of many ocular surface diseases. This paper reviewed
      recent researches on ocular surface related mucins that would provide bases to
      exploring the pathogenesis, diagnosis, and therapeutic tragedies of ocular
      surface diseases.

PMID- 17442174
TI  - [Advances in clinical and molecular genetics of congenital cranial dysinnervation
      disorders].
AB  - Congenital cranial dysinnervation disorders (CCDDs) are congenital non
      progressive, sporadic or familial abnormalities of cranial musculature that
      result from developmental abnormalities of, or the complete absence of, one or
      more cranial nerves with primary or secondary muscle dysinnervation. These
      disorders include vertical disorders of ocular motility, horizontal disorders of
      ocular motility and disorders with abnormalities of facial motility that were
      previously referred to as "congenital fibrosis syndromes". The advances in
      clinical and molecular genetics of congenital cranial dysinnervation disorders
      are reviewed.

PMID- 17442176
TI  - [Differences between the expression of matrix metalloproteinase-2, 9 in
      preeclampsia and normal placental tissues].
AB  - OBJECTIVE: To study the possible relationships between expression of matrix
      metalloproteinase (MMP) 2, 9 and the pathogenesis of preeclampsia in which
      trophoblast invasion is impaired. METHODS: MMP-2, 9 expression were detected by
      immunohistochemistry streptavidin-biotin complex (SABC) method in 20 normal term
      placentae and 20 preeclampsia placentae, respectively. In addition, mRNAs for MMP
      2, 9 were analyzed by real time PCR in both groups. RESULTS: The intensities of
      both MMP-2 and MMP-9 immunostaining in preeclampsia placentae were significantly
      declined compared to those of normal term placentae (P < 0.05). By using 2(
      DeltaDeltaCt) as a relatively quantitative assay, mRNA expression of MMP-2 was
      significantly higher in 10 normal placentae than those in 13 preeclampsia
      placentae (7.6 +/- 2.8 vs 5.6 +/- 1.5, P < 0.05). Expression of MMP-9 mRNA was
      also significantly higher in normal placentae than those in preeclampsia
      placentae (2.2 +/- 2.6 vs -0.9 +/- 2.0, P < 0.05). Whereas, mRNA expression of
      MMP-2 was higher compared to MMP-9 in normal term placentae (P < 0.05).
      CONCLUSION: The decreased expression of MMP-2 and MMP-9 in preeclampsia placentae
      may lead to impaired invasion of trophoblast cells, causing abnormal placentation
      and occurrence of preeclampsia.

PMID- 17442177
TI  - [Screening of differentially expressed genes in placentas with hepatitis B virus
      infection by suppression subtractive hybridization technique].
AB  - OBJECTIVE: To screen differentially expressed genes in placentas with hepatitis B
      virus (HBV) infection and to discuss the molecular mechanism of HBV intrauterine
      infection. METHODS: Thirty placenta tissue specimens from HBsAg and HBV DNA
      positive pregnant women were used as the study group and 30 placenta tissue
      specimens from normal pregnant women with HBsAg and HBV DNA negativity were
      served as the control group. The suppression subtractive hybridization (SSH)
      technique was used. Total RNAs of placenta tissue of the study group were mixed
      as the tester, and total RNAs of placenta tissue of the control group were mixed
      as the driver. A subtractive cDNA library was constructed by PCR-selective cDNA
      subtraction systems. Amplifications of the library were carried out with E. coli
      strain DH5alpha by reverse spot hybridization. RT-PCR confirmed that
      phosphatidylinositol 3-kinase (PI3K) was up-regulated in placenta tissue with HBV
      infection. RESULTS: Colony PCR showed that the clones contained 200 - 1000 bp
      inserts. Thirty five clones were confirmed by reverse spot hybridization and
      analyzed by sequencing and bioinformatics. Thirty three known genes and 2 genes
      with unknown function were obtained. RT-PCR preliminarily confirmed that PI3K
      gene was up-regulated in HBV infected placenta. CONCLUSIONS: The differentially
      expressed genes in placentas with hepatitis B virus (HBV) infection using SSH
      technique has been screened out successfully. These differentially expressed
      genes encoding proteins participating in cell vital metabolism and malformation,
      and signal conduction-antiapoptosis pathway. This finding brings some new clues
      for studying the mechanisms of HBV intrauterine infection.

PMID- 17442178
TI  - [Clinical study on fetal encephalic fluid].
AB  - OBJECTIVE: To discuss the clinical significance of fetal encephalic accumulated
      fluid revealed by prenatal ultrasonography. METHODS: Prenatal ultrasonography was
      performed on 8426 women at more than 20 weeks' gestation. Totally 150 women with
      fetal encephalic accumulated fluid more than 5 mm were included in this study.
      The changes of fetal encephalic accumulated fluid and the associated anomalies
      were observed regularly every 2 weeks until delivery. The live infants were
      followed up regularly. RESULTS: The incidence of fetal encephalic fluid was 1.8%,
      including 72 cases with fluid in the fetal anterior or posterior cornu of
      unilateral ventricle, 46 cases with accumulated fluid in fetal posterior fossa,
      32 cases with fluid in more than 2 sites. Generally, the accumulated fluid in
      fetal encephalus was first diagnosed at 17 - 40 gestational weeks, with a median
      of (26 +/- 5) weeks. Most of them were found between 29 - 32 gestational weeks
      (63 cases, 42.0%), and the maximum amount of accumulated fluid was also found
      between 29 - 32 weeks (70 cases, 46.7%). Spontaneous regression of intracranial
      fluid could be seen in 111 fetuses (74.0%). The period of fluid regression ranged
      from 29 to 40 weeks of gestation, of which the average gestational week was (36
      +/- 2) weeks. Additionally, the most frequent period of regression was in the
      first two thirds of the three trimesters of pregnancy. The incidence of defected
      infants was 3.8%, 10.2% and 67.4%, respectively, when the amount of accumulated
      fluid was less than 10 mm, 10 - 14 mm and more than 15 mm. And the accumulated
      fluid in more than 2 sites was also a risk factor of defected fetuses, with an
      incidence of 60.0%. CONCLUSIONS: Most cases could be diagnosed between 29 - 32
      gestational weeks, and the maximum amount of accumulated fluid is also observed
      in this period. The more fluid in fetal encephalus, the more sites the fluid
      distributed in, the more defected fetuses or infants would be observed. So in
      cases of more than 15 mm of fluid, or accumulated fluid in more than 2 sites,
      anomalies should be observed extremely carefully.

PMID- 17442179
TI  - [Prenatal diagnosis of congenital fetal heart abnormalities in twins by Yagel's
      heart examination method].
AB  - OBJECTIVE: To investigate the value and clinical significance of congenital heart
      diseases (CHD) detection in twins. METHODS: A total of 1103 twins were included
      in this study (127 twins were at high risk for CHD). The fetal hearts were
      scanned by ultrasound using Yagel's heart examination method. Autopsies were done
      when the pregnancy was terminated. And blood samples from fetal hearts or
      umbilical veins were used to evaluate fetal chromosomes. A close follow-up was
      conducted for normal heart cases and another heart examination was done within
      three months after birth. RESULTS: (1) 12 twins (1.09%, 12/1103) had CHD. Among
      them, 4 cases were from the high risk for CHD group (33.3%, 4/12), and 8 cases
      (66.7%, 8/12) were from the low risk pregnancy group. (2) Two twins suffered from
      the same CHD (one pair were both TOF, and the other pair were both rhabdomyoma).
      One pair of twins had different abnormalities (one baby was TOF, and the other
      was duodenal atresia with a normal heart). All three pairs of twins chose
      termination and autopsies were conducted. Unanimous conclusions between prenatal
      ultrasound and autopsy were obtained. Nine twins were CHD in one baby and a
      normal heart in the other baby. Seven of them had the same conclusion after
      delivery. (3) Two twins with CHD were found with fetal abnormal chromosome. (4)
      1091 cases were not found having any abnormality, however, one fetus from one
      twin pair was diagnosed with ventricular septal defect (VSD) with abnormal
      chromosome after birth, and one fetus from another twin pair had patency of
      ductus arteriosus after birth. (5) The sensitivity of Yagel's heart examination
      was 82.4% and specificity was 100% in twins. CONCLUSION: Yagel's heart
      examination is an effective and time-saving method to scan fetal hearts in twins.

PMID- 17442180
TI  - [Effects of nuclear factor-kappaB decoy oligodeoxynucleotide on the function of
      human umbilical artery smooth muscle cells induced by umbilical sera in
      preeclampsia].
AB  - OBJECTIVE: To study the effects of nuclear factor-kappaB (NF-kappaB) decoy
      oligodeoxynucleotide (ODN) on the preeclamptic umbilical serum induced expression
      of precollagen I, III mRNA and tumor necrosis factor-alpha (TNF-alpha) in
      cultured human umbilical artery smooth muscle cells (HUASMC). METHODS: Primary
      cultured HUASMC of normal pregnancy were divided into four groups: group A
      (HUASMC were incubated with umbilical serum of normal pregnancy); group B (HUASMC
      were incubated with umbilical serum of preeclampsia); group C (HUASMC were
      transfected with NF-kappaB cis decoy ODN 48 h before incubation with umbilical
      serum of preeclampsia); group D (HUASMC were transfected with NF-kappaB scramble
      ODN 24 h before incubation with umbilical serum of preeclampsia). NF-kappaB cis
      decoy ODN and NF-kappaB scramble ODN were transfected with cationic lipofectamine
      to the latter two groups, respectively. The proliferation of human umbilical
      artery smooth muscle cells was evaluated by methyl thiazolyl tetrazolium and the
      apoptosis was analyzed by flow cytometry. The expression levels of precollagen I,
      III mRNA were detected by RT-PCR, the expression levels of TNF-alpha were
      detected by western blot. RESULTS: (1) The proliferation of group B (0.19 +/-
      0.02) and group D (0.18 +/- 0.03) was significantly increased as compared with
      those of group A (0.11 +/- 0.02) and group C (0.14 +/- 0.02) (P < 0.05). (2) The
      apoptosis rates of group B [(7.8 +/- 1.3)%], group C [(10.1 +/- 1.2)%] and group
      D [(8.1 +/- 1.3)%] were significantly reduced as compared with that of group A
      [(14.3 +/- 1.2)%] (P < 0.05), and there was a significant difference between
      groups B and C (P < 0.05). (3) The expression levels of precollagen I mRNA of
      group B (0.31 +/- 0.04), group C (0.23 +/- 0.04) and group D (0.30 +/- 0.03) were
      significantly increased as compared with that of group A (0.16 +/- 0.02) (P <
      0.05), and there was a significant difference between groups B and C (P < 0.05).
      (4) There were no significant differences among the four groups in the expression
      level of precollagen III mRNA (P > 0.05). (5) The expression of TNF-alpha of
      group B (0.74 +/- 0.11), group C (0.36 +/- 0.09) and group D (0.79 +/- 0.12) were
      significantly higher than that of group A (0.15 +/- 0.03) (P < 0.05), and the
      expression of TNF-alpha of groups B and D were significantly higher than that of
      group C (P < 0.05), while there was no significant difference between groups B
      and D (P > 0.05). CONCLUSIONS: NF-kappaB cis decoy ODN could down-regulate the
      proliferation, as well as the expression levels of precollagen and TNF-alpha of
      HUASMC induced by umbilical serum of preeclampsia. NF-kappaB may play an
      important role in the pathogenesis of placental artery abnormalities in
      preeclampsia.

PMID- 17442181
TI  - [Outcome analysis of stage III - IV endometriosis after conservative surgery].
AB  - OBJECTIVE: To analyze the recurrence and fertility outcome of stage III - IV
      endometriosis after conservative surgery. METHODS: A retrospective study was
      performed on 90 women with stage III - IV endometriosis who had been diagnosed by
      pathology after conservative surgery. They were divided into three groups: 16
      without endocrine therapy (Group A), 52 treated with gestrinone (Group B), 22
      treated with gonadotropin releasing hormone agonist (GnRHa) (Group C). The number
      of infertile patients in the three groups was 10, 15 and 10, respectively. The
      recurrent and pregnant outcomes were compared after a median follow-up of 48.5
      months (2 - 7 years). RESULTS: The recurrent rate of groups A, B, and C was 18.8%
      (3/16), 30.8% (16/52) and 13.6% (3/22), respectively (P = 0.247); the recurrent
      time in the three groups were Group A: 63.8 months, Group B: 63.3 months, and
      Group C: 47.6 months (P = 0.376). There were no significant differences in
      pregnant outcome among the three groups. The cumulative pregnant rates were 70.0%
      (7/10), 66.7% (10/15) and 60.0% (6/10), respectively (P = 0.890). There was also
      no difference in the first pregnant interval after surgery (P = 0.092) and 65.2%
      of the patients acquired pregnancy spontaneously in the first year after surgery.
      CONCLUSIONS: Neither gestrinone nor GnRHa can prolong the recurrent time or
      reduce the recurrent rate after conservative surgery. Surgery can improve the
      fertility ability of stage III and IV endometriosis patients; however, the
      pregnant rate cannot be improved with endocrine therapy after conservative
      surgery.

PMID- 17442182
TI  - [Study on the expression of transcription factor GATA-3 and T-bet mRNA in decidua
      of women with unexplained recurrent spontaneous abortion].
AB  - OBJECTIVE: To investigate the roles of transcription factor GATA-3 and T-bet at
      the fetal-maternal interface in the pathogenesis of unexplained recurrent
      spontaneous abortion (URSA). METHODS: The expression of GATA-3 and T-bet mRNA was
      examined by in situ hybridization. Decidua was obtained from 20 women with URSA
      and 20 normal pregnant (NP) women. RESULTS: (1) The number of GATA-3 positive
      cells per high power field in women with URSA (25 +/- 16) was significantly lower
      than those in NP women (38 +/- 16) (P < 0.05). (2) The number of T-bet positive
      cells per high power field in women with URSA (59 +/- 17) was significantly
      higher than those in NP women (46 +/- 18) (P < 0.05). (3) Numbers of cells
      expressing GATA-3 mRNA correlated significantly with T-bet mRNA positive cell
      numbers in decidua (r = -0.55, P < 0.01). CONCLUSIONS: The results demonstrate
      that upregulated expression of T-bet and downregulated expression of GATA-3 are
      found in the decidua of women with URSA. Imbalance of GATA-3/T-bet transcription
      factors might interfere with type 1 helper T cell (Th1)/type 2 helper T cell
      (Th2) differentiation at the fetal-maternal interface and cause URSA.

PMID- 17442183
TI  - [Study on the peritoneal dissemination of endometrial cells during hysteroscopy].
AB  - OBJECTIVE: To study prospectively the likelihood and the affecting factors of
      endometrial cell dissemination into the peritoneal cavity during hysteroscopic
      procedures. METHODS: A total of 121 patients with benign endometrial pathology
      underwent hysteroscopy combined with laparoscopy. All the patients had pelvic
      washings performed just before and after the procedure of hysteroscopy. We
      collected the peritoneal washings and analyzed the peritoneal cytology changes in
      both groups pre- and post-hysteroscopy, as well as the dissemination rate related
      to the time of hysteroscopy, the intrauterine distention pressure, the volume of
      distention media, and the feature of endometrial conditions. RESULTS: The ratio
      of positive endometrial cells in the peritoneal washings of post-hysteroscopy
      group was 51.2% (62/121), which was significantly higher than pre-hysteroscopy
      group, 38.0% (46/121) (P < 0.01). The mean operation time in the group of
      positive peritoneal cytology was (38 +/- 16) min, longer than the negative group
      (P < 0.05). However, there was no significant difference between the two groups
      with regard to the total volume of distention media, the distention pressure, and
      the endometrial feature (P > 0.05). CONCLUSIONS: Hysteroscopic procedures may
      have a risk of disseminating the endometrial cells into peritoneal cavity. Under
      a certain uterine distention pressure, the rate of dissemination is correlated
      with hysteroscopic duration.

PMID- 17442184
TI  - [Tissue injury observation caused by thermal effects of microwave endometrial
      ablation].
AB  - OBJECTIVE: To investigate the thermal effects on tissue structures during
      microwave endometrial ablation (MEA) and seek a feasible method of endometrial
      thinning and a fitting mode of applicator radiating microwaves. METHODS:
      Operations were performed between the group of thorough uterine curettage and the
      group of early follicular phase in in vitro or in vivo uterus. The former was
      treated with MEA after thorough uterine curettage; while the latter was treated
      with MEA in the early follicular phase directly. The applicator radiating
      microwaves were moved in "Z" or "Z + W" shape inside uterine cavity. At the same
      time the serosal temperature was measured in the uterine fundus, tael cornua
      uteri, the posterior wall and the lower part of anterior wall. After operations
      the uterine specimens were stained by hematoxylin-eosin, and respiratory enzyme
      dehydronicotinamide adenine dinucleotide phosphate diaphorase (NADH-d) methods.
      The morphologic changes and the depth of tissue thermal damage were evaluated
      using an optical microscope and electron microscope. RESULTS: (1) Under the
      optical microscope the endometrial glands became distorted, the cell boundaries
      disappeared, the nucleoli turned condensed and were stained darker. A large
      number of acute inflammatory cells appeared in fibrous tissue. In the shallow
      muscle layer cells were arrayed thickly, nucleoli were solidified and condensed,
      and cellular plasm were concentrated. The endometrial and the superficial muscle
      layers were damaged and colorless with NADH-d staining. The scope of the tissue
      thermal damage was clearly seen. Under an electron microscope, some smooth muscle
      cells, chromatin, karyotheca and cellular membranes were destroyed. The
      mitochondria were swollen, membranes were ruptured, and the crista disappeared.
      Many organelles were destroyed. The chromatin was lightly wrecked in the
      transitional area between putrescence and the normal smooth muscle tissue.
      Karyotheca and cellular plasm still existed, the mitochondria were highly
      edematous and the crista were disappeared, and the granular endoplasmic reticula
      were slightly expanded and degranulated. (2) The serosal temperature in in vitro
      uterus was significantly higher than that in in vivo uterus (P < 0.01). However,
      the highest temperature in in vitro or in vivo uterus were all taken in the
      posterior wall, being 50.9 degrees C and 37.6 degrees C, respectively. (3) The
      injury depth in in vitro uterus was 4.0 - 8.8 mm in the uterine body, 1.6 - 3.8
      mm in the cervix uteri-uterine body junction; while those of in vivo uterus were
      4.1 - 6.6 mm, 0 - 2.8 mm, respectively. The highest injury depth of tissue was in
      the posterior wall, significantly different from the other parts (P < 0.01). The
      injury depth of the corresponding part in in vitro or in vivo uterus all had a
      significant difference (P < 0.05). The depth of thermal damage had no significant
      difference between the group of thorough uterine curettage and the group of early
      follicular phase (P > 0.05). The injury depth of the "Z + W" radiation group
      increased significantly than that of the "Z" radiation group (P < 0.05).
      CONCLUSIONS: (1) The depth of thermal damage is safe and controllable. (2) MEA
      with preoperative thorough uterine curettage or scheduling treatment at the
      follicular phase is efficient. (3) It is the ideal performing mode that the
      applicator radiating microwaves move in "Z + W" shape inside uterine cavity. (4)
      The thermal damage of MEA occurs more frequently in the portion with a shortage
      of blood supply.

PMID- 17442185
TI  - [Evaluation of the follow up results of patients with cervical intraepithelial
      neoplasia III after surgical treatment].
AB  - OBJECTIVE: To evaluate the follow-up results of patients with cervical
      intraepithelial neoplasia III (CIN III) after surgical treatment. METHODS: A
      retrospective analysis of consecutive patients with CIN III after surgical
      treatment between Jan 1st, 1999 and Jun 30th, 2004 was performed. The follow-ups
      of the patients after surgical treatment were assessed. RESULTS: In the follow-up
      of patients with CIN III after surgical treatment, the rate of abnormal cytology
      was 9.3%. The rate of follow-up was higher in patients with cervical conization
      than in patients with initial hysterectomy and in patients of the oncological
      group than of the non-oncological group. The rate of follow-up was lower in
      patients over 40 years old. There was no difference in the residential areas of
      the patients. CONCLUSIONS: Cytological follow-up of patients with CIN III after
      operation is varied. The rate of follow-up is lower in patients over 40 years
      old, in patients having initial hysterectomy and in patients of the non
      oncological group. The rate of follow-up is associated with the knowledge about
      CIN of both surgeons and patients.

PMID- 17442186
TI  - [Intermediate-conductance-Ca2+-activated K+ channels are overexpressed in
      endometrial cancer and involved in regulating proliferation of endometrial cancer
      cells].
AB  - OBJECTIVE: To study the expression of intermediate-conductance-Ca(2+)-activated
      K(+) (IKCa1) channels in endometrial cancer and its role in regulating
      proliferation of endometrial cancer cells. METHODS: Western blot and RT-PCR were
      used to examine the expression of IKCa1 channels in 13 normal endometrial
      specimens and 25 endometrial cancer specimens; and RNA interference (RNAi),
      [(3)H] thymidine incorporation, and inhibitor of IKCa1 channel were used to
      explore the role of IKCa1 channels in regulation of proliferation of endometrial
      cancer cells HEC-1A. RESULTS: The expression rate and level of IKCa1 mRNA in
      endometrial carcinoma (84%, 0.89 +/- 0.52) were higher than in normal endometria
      (8%, 0.14 +/- 0.12; P < 0.01). The expression rate and level of IKCa1 protein in
      endometrial carcinomas (80%, 1.18 +/- 0.41) were higher than in normal endometria
      (15%, 0.71 +/- 0.26; P < 0.01). Clotrimazole, an inhibitor of IKCa1 channels
      known to suppress the function of the channels, caused a both time- and dose
      dependent decrease in cell number of HEC-1A cell. Western blot analysis revealed
      that the IKCa1 level in whole lysates of the cells transfected with target-IKCa1
      small interference RNA (siRNA) was (48.27 +/- 9.07)% of that found in the cells
      transfected with non-silencing RNA; [(3)H] thymidine incorporation in HEC-1A
      cells transfected with target-IKCa1 siRNA was also reduced, siRNA inhibited HEC
      1A cell proliferation, compared with the cells transfected with non-silencing RNA
      (P < 0.05). CONCLUSION: The expression of IKCa1 channels may be closely related
      to the proliferation of endometrial cancer, and down regulation of its expression
      may suppress its development.

PMID- 17442187
TI  - [Polymorphism of catechol-O-methyltransferase gene in relation to the risk of
      endometrial cancer].
AB  - OBJECTIVE: The 4- and 16-hydroxylated metabolites of estrogens have been
      implicated in carcinogenesis, whereas its 2-hydroxylated metabolites have been
      shown to have antiangiogenic effects. We aimed to examine whether the
      polymorphisms of catechol-O-methyltransferase (COMT) involved in the estrogen
      metabolism are associated with endometrial cancer risk. METHODS: Polymerase chain
      reaction-restrictive fragment length polymorphism (PCR-RFLP) analysis was used to
      study the variant allele frequency distributions of COMT Val158Met genetic
      polymorphism in a population based case-control study with 132 endometrial cancer
      cases and 110 controls. Odds ratios (OR) and 95% confidence intervals (CI) were
      estimated by unconditional logistic regression after adjustment for known or
      suspected risk factors for endometrial cancer. RESULTS: The most frequent
      genotype was COMT(Val/Val) (47.2%, 52/110) in control group and COMT(Val/Met)
      (58.3%, 77/132) in endometrial cancer group. The difference between the two
      groups was of statistical significance (P < 0.05). Compared with COMT(Met/Met)
      genotype, the COMT(Val/Val) genotype was inversely correlated with endometrial
      cancer risk, and the adjusted OR value was 0.262 (95% CI: 0.080 - 0.862, P =
      0.027). CONCLUSIONS: Among the genotypes in women in South China, genotype
      COMT(Val/Val) is mostly seen, followed by COMT(Val/Met), and COMT(Met/Met) is the
      least in control group. The endometrial cancer susceptivity of genotype
      COMT(Val/Val) carriers may be lower than COMT(Met/Met) carriers.

PMID- 17442188
TI  - [Modified tubo-uterine implantations for proximal tubal occlusive infertility
      after femal sterilization with mucilago phenol].
AB  - OBJECTIVE: To explore the effects of modified tubo-uterine implantations
      performed on women with proximal tubal occlusive infertility after femal
      sterilization with mucilago phenol. METHODS: Two hundred and eight infertile
      women who were admitted to the Second Affiliated Hospital of Sun Yat-sen
      University between 1986 and 2004 were included. They all accepted modified tubo
      uterine implantation after occlusion of fallopian tubes with mucilago phenol.
      RESULTS: It was found that the occlusions were all located in the interstitial
      portion or isthmic portion of the fallopian tubes. Different degrees of pelvic
      adhesions were found in 65 cases. Fifty-seven cases were slightly adhesive, seven
      cases were of moderate degree and one case was severe. One hundred and ninety
      nine cases were followed up after operations (95.7%). One hundred and ninety
      three women accepted hydrotubation in the following month just after the
      operation and 185 women were found to be unobstructed (95.8%). One hundred and
      forty-three women became pregnant, the pregnant rate being 71.9% (143/199). One
      hundred and twenty-five women had term deliveries (87.4%), three women were in
      early pregnancy and two in midtrimester pregnancy. Eleven women had spontaneous
      abortion (7.7%). Two women had tubal pregnancy (1.0%). None of the 199 cases had
      any signs of endometriosis. CONCLUSIONS: Modified tubo-uterine implantations are
      quite effective for proximal tubal occlusive infertility. It may be a favorable
      method for such kind of tubal occlusions.

PMID- 17442189
TI  - [Inhibition of ovarian cancer growth by small interfering RNA targeting X-linked
      inhibitor of apoptosis gene].
AB  - OBJECTIVE: To construct an RNA interference vector to down-regulate X-linked
      inhibitor of apoptosis (XIAP) gene and study the RNA interference effect on the
      cell cycle and growth of ovarian cancer. METHODS: Oligonucleotides of 64 base
      pairs for hairpin RNA targeting XIAP were designed, chemically synthesized,
      annealed, and cloned into the pSUPER vector. After identification by restriction
      digestion, the correct vectors were transiently transfected into SKOV3 cells, a
      human ovarian cancer cell line. The XIAP mRNA was detected by RT-PCR. The
      proteins were detected by western blot and indirect immunofluorescence staining.
      Flow cytometry (FCM) analysis and methyl thiazolyl tetrazolium (MTT) assay method
      were applied to measure cell cycle, cell growth and sensitiveness to cisplatin.
      RESULTS: SKOV3 cells had a high level expression of XIAP. The vector of RNA
      interference, which can interfere with XIAP gene was successfully constructed.
      After transient transfection, the expression of XIAP protein was significantly
      decreased in SKOV3 cells and the value of relative density was 3584 +/- 124, 2138
      +/- 65, 1973 +/- 80 and 110 +/- 12, respectively (P = 0.0334). At the same time,
      the expression of XIAP mRNA was decreased accordingly and the value of relative
      density was 6674 +/- 274, 4532 +/- 107, 2322 +/- 57 and 1864 +/- 78, respectively
      (P = 0.0127). The FCM results showed that, the vector could increase the number
      of cells in G(1) phase compared with parent cells and compared with the cells
      transfected with pSUPER (P < 0.05); the number in S phase decreased compared with
      parent cells and compared with the cells transfected with pSUPER (P < 0.05). MTT
      results showed that pSUPER-siXIAP could inhibit the growth and proliferation of
      SKOV3 cells in a time-dependent manner, and inhibit the tumor cell growth.
      CONCLUSIONS: We successfully constructed an expressing hairpin RNA against the
      XIAP vector. The vector can effectively silence XIAP gene, increase the number of
      cells in G(1) phase, and slow down the growth of tumor cells. This may be a
      useful therapeutic strategy for XIAP over-expressing ovarian carcinomas.

PMID- 17442197
TI  - Late stent thrombosis: a not negligible issue after drug-eluting stent
      implantation.

PMID- 17442198
TI  - Sirolimus-eluting cobalt alloyed stents in treating patients with coronary artery
      disease: six-month angiographic and one-year clinical follow-up result. A
      prospective, historically controlled, multi-center clinical study.
AB  - BACKGROUND: The emergence of drug-eluting stents (DES) has dramatically reduced
      the incidence of in-stent restenosis. This study was conducted to evaluate the
      safety and efficacy of sirolimus-eluting cobalt-chrome stents (Firebird 2) for
      treating patients with coronary artery disease. METHODS: Sixty-seven patients
      with de novo or non-stented restenostic coronary lesions were chosen to receive
      the Firebird 2 stent as the final treatment (Firebird 2 group). Another 49
      consecutive patients were implanted with bare cobalt alloyed stents (Driver,
      Medtronic) within the previous six months and served as historical controls
      (control group). Baseline clinical characteristics, angiographic features,
      procedural results, 30-day, 6-month and 12-month clinical follow-up regarding the
      occurrence of major adverse cardiac events (MACE), as well as the primary
      endpoint of late lumen loss at 6-month angiographic follow-up were compared
      between the two groups. RESULTS: The demographic characteristics were similar
      between the two groups despite more patients in the Firebird 2 group who
      underwent previous percutaneous coronary intervention (22.4% vs 8.2%, P = 0.0418)
      and who had diabetes mellitus (29.9% vs 12.2%, P = 0.0253). In the Firebird 2
      group, the mean diameter of the reference vessel was smaller ((2.79 +/- 0.46) mm
      vs (2.98 +/- 0.49) mm, P = 0.0175) and more stents were implanted for each lesion
      (1.28 +/- 0.52 vs 1.10 +/- 0.30, P = 0.0060). Other angiographic, procedural
      results and the device success rate were similar between the two groups. The MACE
      rate at 30-day and 3-month was the same, but significantly fewer MACE occurred in
      the Firebird 2 group at 6- and 12-month follow-up (1.5% vs 12.2% at 6 month, P =
      0.0168; 1.5% vs 26.5% at 12 month, P < 0.0001). The primary endpoint of late
      lumen loss at 6-month angiographic follow-up was significantly reduced in the
      Firebird 2 group (in-stent: (0.05 +/- 0.09) mm vs (0.98 +/- 0.61) mm; in-segment:
      (0.05 +/- 0.18) mm vs (0.72 +/- 0.59) mm; P < 0.0001) than the control group. One
      patient in the Firebird 2 group had in-segment restenosis (1.3%) while the rate
      in the control group (38.1%) was significantly higher, P < 0.0001. Intravascular
      ultrasound examination was performed in 70.1% of patients in the Firebird 2 group
      and revealed that the percentage of volumetric obstruction was (1.26 +/- 1.05)%.
      No stent thrombosis was observed in either group at 12-month follow-up.
      CONCLUSION: The Firebird 2 sirolimus-eluting cobalt alloyed stent is safe and
      feasible in treating patients with coronary artery disease.

PMID- 17442199
TI  - Comparison of immediate and followup results between transradial and transfemoral
      approach for percutaneous coronary intervention in true bifurcational lesions.
AB  - BACKGROUND: A comparison of efficacy and safety between transradial and
      transfemoral approach for percutaneous coronary intervention (PCI) in
      bifurcations has not been done. This study evaluated feasibility of transradial
      PCI (TRI) and compared the immediate and followup results with transfemoral PCI
      (TFI) in bifurcations. METHODS: One hundred and thirty-four consecutive patients
      with bifurcations were treated with PCI in our hospital from April 2004 to
      October 2005. Of these, there were 60 patients (88 lesions) in TRI group and 74
      patients (101 lesions) in TFI group. Bifurcations type was classified according
      to the Institut Cardiovasculaire Paris Sud Classification. RESULTS: TRI group had
      smaller stent diameter ((3.06 +/- 0.37) mm vs (3.18 +/- 0.35) mm, P = 0.023) and
      postprocedural in-stent minimum lumen diameter ((2.62 +/- 0.37) mm vs (2.74 +/-
      0.41) mm, P = 0.029) than TFI, but there were not significant differences in in
      stent subacute thrombosis rate (0% vs 1.0%, P = 0.349), target lesion
      revascularization (TLR) (0% vs 1.0%, P = 0.349) following procedure and
      thrombosis (2.3% vs 1.0%, P = 0.482), in-stent restenosis (12.5% vs 10.9%, P =
      0.731), in-segment restenosis (17.0% vs 14.9%, P = 0.681), TLR (10.2% vs 13.9%, P
      = 0.446) and TLR-free cumulative survival rate (89.8% vs 86.1%, P = 0.787) at
      seven months followup. No death was reported in the two groups. CONCLUSION:
      Transradial intervention is feasible and appears to be as effective and safe as
      transfemoral PCI in treatment of true bifurcational lesions.

PMID- 17442200
TI  - Long-term outcomes following drug-eluting stent implantation in unprotected left
      main bifurcation lesions.
AB  - BACKGROUND: The safety and efficacy of drug-eluting stents (DES) implantation in
      unprotected left main (LM) bifurcation lesions has yet to be determined. The aim
      of the present report was to evaluate the long-term outcome following
      implantation of DES in unprotected LM bifurcation lesions. METHODS: We identified
      70 consecutive patients treated with DES in unprotected LM bifurcation lesions
      from April 2003 to January 2005. Of them, 42 patients were treated with sirolimus
      eluting stent (SES) and 28 patients were treated with paclitaxel-eluting stent
      (PES). RESULTS: Stents to the left anterior descending and to the circumflex were
      implanted in 62 patients. During 1-year follow-up, 3 (4.3%) patients died of
      cardiac causes. One of them had myocardial infarction and adjudicated as possibly
      due to stent thrombosis. Angiographic follow-up was available in 80% of patients.
      The per lesion restenosis rate was 13.4% in the entire cohort, of which 10.7%
      occurred in lesions treated with SES and 16.1% in those treated with PES (P =
      0.58). All restenosis was focal and occurred in the lesions treated with a stent
      with stent size to post-procedural reference vessel diameter ratio < 1.0 (17.6%
      vs 0, P = 0.04). The per patient target lesion revascularization rate at 1 year
      was 17.1%. One year survival free from major adverse cardiac events was 77.1%.
      CONCLUSIONS: Treatment of LM bifurcation lesions using DES is a safe and feasible
      way with a low one-year mortality. The need for revascularization in 17% of
      patients demands for improvement.

PMID- 17442201
TI  - Midterm outcomes of prospective, randomized, single-center study of the Janus
      tacrolimus-eluting stent for treatment of native coronary artery lesions.
AB  - BACKGROUND: Long-term efficacy and safety of tacrolimus-eluting stent (Janus) for
      treatment of coronary artery disease in percutaneous coronary interventions (PCI)
      "real world" is uncertain. The aim of this study was to evaluate the efficacy and
      safety of Janus stent for treating coronary heart disease in PCI daily practice,
      the safety of 4-month clopidogrel therapy after Janus stent implantation and the
      feasibility for treating patients with acute myocardial infarction (AMI) for
      first time. METHODS: From February 20, 2006 to August 26, 2006, a total of 200
      patients were enrolled and randomly assigned to receive either Janus stent (n =
      100) or bare metal stent (Tecnic Carbostent, n = 100). All patients were
      administered with clopidogrel for 4 months and aspirin for life long after
      stenting. RESULTS: Baseline clinical and angiographic characteristics were
      comparable between the two groups. AMI was present in 37% of patients with Janus
      and 36% with Tecnic Carbostent. At an average of 246-day follow-up, major adverse
      cardiac events (MACE) was 6% with the Janus stent and 15% with the Tecnic
      Carbostent (P = 0.038). Primary events included 1 cardiac death, 1 myocardial
      infarction (MI) due to subacute stent thrombosis and 13 target lesion
      revascularizations (TLR) due to restenosis in patients with Tecnic Carbostent and
      6 TLR due to restenosis in patients with Janus stent. Although all patients had
      discontinued clopidogrel for an average of 126 days, there was no additional
      thrombotic event in the two groups. CONCLUSIONS: Janus stent is efficient in
      reducing MACE compared with Tecnic Carbostent at an average of 8-month follow-up.
      Discontinuation of clopidogrel at 4 months after PCI is safe for patients with
      Janus stent, including AMI patients. Long-term efficacy of Janus stent in
      reducing restenosis requires further study.

PMID- 17442202
TI  - Diver CE versus Guardwire Plus for thrombectomy in patients with inferior
      myocardial infarction: a trial of aspiration of thrombus during primary
      angioplasty for inferior myocardial infarction.
AB  - BACKGROUND: Different feasible and safe thrombectomy and distal protection
      devices have been used in clinical practice. The efficiency and safety of adjunct
      thrombectomy using Diver CE device (Invatec, Italy) versus Guardwire Plus device
      (Medtronic, USA) before percutaneous coronary intervention (PCI) were compared in
      patients with acute inferior ST-segment-elevation myocardial infarction (STEMI)
      for less than 12 hours, thrombolysis in myocardial infarction (TIMI) flow grade 0
      to 1, and total occlusion of the proximal right coronary artery (= 3 mm in
      diameter) in a prospective randomized single-center study. METHODS: The primary
      end point was the magnitude of ST-segment resolution (STR) (> 70%) measured
      immediately, 90 minutes and 6 hours after PCI, myocardial blush grade and slow
      flow or no-reflow. Secondary end points were left ventricular end-diastolic
      volume (LVEDV), left ventricle ejection fraction (LVEF) and major adverse cardiac
      events (MACEs) including death, myocardial infarction, target vessel
      revascularization and stroke at 30 days. RESULTS: A total of 122 patients were
      equally divided into Diver CE group and Guardwire Plus group, which were
      comparable by age ((60 +/- 14) years vs (60 +/- 13) years), male (82% vs 84%),
      diabetes (31% vs 28%), previous coronary artery disease (25% vs 23%), onset-to
      angiogram ((350 +/- 185) min vs (345 +/- 180) min), and use of glycoprotein
      IIb/IIIa inhibitor (11% vs 13%). The magnitude of ST-segment resolution was
      similar in the two groups as ST-segment resolution > 70% (57% vs 59%; P > 0.05).
      Similar slow flow/no-reflow rates were observed in the Diver CE group (8%) and
      the Guardwire Plus group (7%). TIMI flow grade 3 was obtained in 95% vs 97%
      patients, respectively (P > 0.05). Myocardial blush grade 3 was similar (70% vs
      72%; P > 0.05). Thirty-day clinical outcome was comparable (LVEF, 0.54 +/- 0.12
      vs 0.53 +/- 0.11; death, 3% vs 3%; myocardial infarction, 2% vs 0%; and target
      vessel revascularization, 2% vs 2%; P > 0.05, respectively). CONCLUSIONS: Removal
      of thrombus burden with the Diver CE catheter before stenting leads to similar
      improvement of myocardial reperfusion in patients with inferior STEMI and total
      occlusion of the proximal right coronary artery (= 3 mm in diameter) compared
      with the Guardwire Plus device, as illustrated by a reduced risk of distal
      embolization and improved ST-segment resolution.

PMID- 17442203
TI  - Left ventricular endocardial pacing predicts the reduction of left ventricular
      outflow tract pressure gradient immediately after percutaneous transseptal
      myocardial ablation in patients with hypertrophic obstructive cardiomyopathy
      refractory to medication.
AB  - BACKGROUND: Hypertrophic obstructive cardiomyopathy (HOCM) carries an increased
      risk for sudden cardiac death. No data regarding the percutaneous transseptal
      myocardial ablation (PTSMA) and epicardial left ventricular pacing (LVP) were
      reported. METHODS: Seven patients with recurrent symptoms and increased resting
      left ventricular outflow tract pressure gradient (LVOTG) after PTSMA and another
      14 patients with HOCM without history of PTSMA were studied. Both resting and
      dobutamine stress echocardiography, PTSMA and LVP were routinely performed.
      RESULTS: In patients without previous PTSMA procedure, mild reduction of resting
      LVOTG was detected at 5 minutes after left ventricular pacing, and this reduction
      became significant at 10 minutes. All patients were divided into successful and
      unsuccessful groups according to their response to LVP. In contrary to patients
      in unsuccessful group, resting and R-S2 stimuli-induced LVOTG during PTSMA
      procedure were decreased dramatically ((9 +/- 5) mmHg vs (58 +/- 12) mmHg, (12 +/
      2) mmHg vs (113 +/- 27) mmHg, P < 0.001). Analysis of Logistic regression
      demonstrated that only LVOTG level during left ventricular pacing was an
      independent factor predicting the reduction of LVOTG immediately after PTSMA
      (odds ratio (OR), 0.59; 95% CI 2.67 to 5.82; P = 0.0002). CONCLUSION: Left
      ventricular endocardial temporary pacing plays a critical role in predicting
      acute effect on the reduction of LVOTG immediately after PTSMA procedure.

PMID- 17442204
TI  - Drug-eluting stent for the treatment of small coronary lesion: comparison between
      sirolimus- and paclitaxel-eluting stent.
AB  - BACKGROUND: Patients with small coronary lesions are at increased risk for repeat
      interventions after coronary angioplasty and stenting. The efficacy of drug
      eluting stents (DES) has been demonstrated to improve the outcomes of these
      patients and is a focus of interest. Currently, two platforms of DES are
      available (sirolimus-eluting stent (SES) and paclitaxel-eluting stent (PES)).
      However, it has less been known that DES, SES vs PES, is superior for the
      treatment of small coronary lesions. METHODS: In this retrospective study, 87
      consecutive patients with 151 lesions underwent implantation of coronary SES (n =
      68) and PES (n = 83). Quantitative coronary angiography (QCA) was performed at
      the time of stent implantation and subsequently at 8 months post-stenting. Small
      vessel disease was defined as lesions in vessels with diameter 2.5 mm measured by
      QCA. Major adverse cardiac events (MACE) including death, thrombosis, nonfatal
      myocardial infarction and target lesion revascularization (TLR) were compared
      between the two groups. RESULTS: Baseline clinical characteristics and
      angiographic parameters were similar between the two groups. At clinical and
      angiographic follow-up, overall thrombosis rates were similar in both groups (0
      vs 1.2%, P > 0.05). The TLR and in-segment restenosis were not significantly
      different (19.1% vs 25.3%; 10.3% vs 10.8%, P = 0.365 and P = 0.913 respectively)
      between the two groups. The in-stent restenosis rate, however, was significantly
      higher in the PES group (4.4% vs 21.7%; P = 0.002). Similarly, the late loss was
      significantly higher in the PES group ((0.140.38) mm vs (0.490.61) mm; P <
      0.001). CONCLUSIONS: In this small sample-size, non-randomized study, the data
      indicated that implantation of SES for the treatment of patients with small
      coronary lesion showed more favorable results in respect of restenosis compared
      with PES implantation.

PMID- 17442205
TI  - A comparison of clinical and angiographic outcomes after Excel bioabsorbable
      polymer versus Firebird durable polymer rapamycin-eluting stent for the treatment
      of coronary artery disease in a "real world" setting: six-month follow-up
      results.
AB  - BACKGROUND: Several clinical trials have shown that rapamycin-eluting stents
      significantly reduce the risk of restenosis after percutaneous coronary
      intervention (PCI). The Firebird stent and the Excel stent (coated with
      bioabsorbable polymer) are two different types of rapamycin-eluting stents made
      in China, both have been recently approved for clinical use in China by State
      Food and Drug Administration. However, it is unclear whether there are
      differences in safety and efficacy between the two types of stents in daily
      practice. METHODS: In the month of June 2006, a total of 190 consecutive patients
      were treated exclusively with Firebird stents (n = 93, Firebird group) or Excel
      stents (n = 97, Excel group) in our center and were included in this study. The
      frequency of major adverse cardiac events (MACE, a composite of death, myocardial
      infarction or target lesion revascularization), binary restenosis, and late lumen
      loss and stent thrombosis during a six-month follow-up period were compared
      between the two groups. RESULTS: Patient and lesion characteristics were
      comparable between the groups. Major adverse cardiac event rates were low in
      hospital and at 6 months (2.1% in the Excel group and 0% in the Firebird group, P
      > 0.05). The 6-month angiographic in-stent restenosis rate was 0% in both groups,
      with an associated late loss of (0.15 +/- 0.21) mm versus (0.14 +/- 0.20) mm (P =
      0.858) and the in-segment restenosis rate was also 0% for the Excel group and the
      Firebird group. There was no definite stent thrombosis identified in either group
      during the six-month follow-up period and only one patient in the Excel group had
      probable stent thrombosis in hospital. CONCLUSIONS: Results from this mid-term,
      single-center study showed that both of the Firebird and the Excel rapamycin
      eluting stent had similar effects on reducing the incidence of MACE and the risk
      of restenosis (both in-stent and in-segment binary restenosis) after PCI in daily
      practice.

PMID- 17442206
TI  - Heat shock protein 70 gene transfection protects rat myocardium cell against
      anoxia-reoxygeneration injury.
AB  - BACKGROUND: A number of studies suggest that the expression of heat shock protein
      70 (HSP(70)) induced by heat stress are associated with protection against
      ischemia-reperfusion injury. But the protective effects may be contaminated by
      other factors in the same stress. This study was conducted to explore the
      protective role of HSP(70) expression in acute myocardial anoxia/reoxygeneration
      (A/R) injury with a liposome-mediated gene transfer technique for the
      introduction of pCDNA HSP(70) into the neonatal rat myocardial cells. In
      addition, heat shock stress cytoprotection was also investigated for comparison.
      METHODS: The cultured primary neonatal rat myocardiocytes with an acute
      myocardial A/R injury model and the HS-treated rat myocardiocyte model were used.
      Three-day cultured myocardiocytes were randomly divided into four groups (n = 8):
      control group, A/R group, HS + A/R group and pCDNA HSP(70) + A/R group. A
      liposome-coated HSP(70) pCDNA plasmid was transfected into the primary neonatal
      rat myocardiocytes; HSP(70) mRNA and its protein were confirmed by reverse
      transcriptase polymerase chain reaction (RT-PCR) and Western blotting. The cell
      viability was assayed by monotetrazolium (MTT) and the lactate dehydrogenase
      (LDH) and creatine phosphokinase (CPK) activity of cells during incubation and
      the changes in cells ultrastructure were examined. NF-kappaB activity in the
      primary neonatal rat myocardiocytes was measured with flow cytometry. RESULTS:
      Compared with viability in the A/R group ((35.4 +/- 6.9)%) the cell viability in
      the HS + A/R group ((72.8 +/- 11.6)%) and the pCDNA HSP(70) + A/R group ((76.3 +/
      12.2)%) was improved significantly (P < 0.05). The activity of LDH and CPK was
      significantly elevated in the A/R group. However, in the HS + A/R group and pCDNA
      HSP(70) + A/R group, significant decreases in activity were observed. The cell
      ultrastructure of the A/R group cells was abnormal, whereas nearly normal
      ultrastructure was observed in HS + A/R group and pCDNA HSP(70) + A/R group.
      HSP(70) mRNA and protein were slightly expressed in the myocardiocytes of the A/R
      group. However, obvious overexpression was observed in the HS + A/R group and in
      the pCDNA HSP(70) + A/R group (P < 0.01). And there was a significant difference
      between the HS + A/R group and the pCDNA HSP(70) + A/R group in the expression of
      HSP(70) mRNA and protein (P < 0.01). A high activity of NF-kappaB (5.76 +/- 0.64)
      was detected in the A/R group. But in the HS + A/R group there was a
      statistically significant decrease in the activity of NF-kappaB compared with the
      A/R group (3.11 +/- 0.52 vs 5.76 +/- 0.64, P < 0.01). The same statistically
      significant difference was also observed in the pCDNA HSP(70) + A/R group and A/R
      group (2.83 +/- 0.49 vs 5.76 +/- 0.64, P < 0.01). CONCLUSIONS: Overexpression of
      HSP(70) alone by gene transfection leads to protection for cardiac myocyte
      against anoxia-reoxygeneration. These cardioprotective effects were related to
      the reduction in activation of NF-kappaB.

PMID- 17442207
TI  - Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and
      angiogenesis of ovarian cancer.
AB  - BACKGROUND: Ginsenoside Rg3, the main component isolated from ginseng, inhibits
      some kinds of tumour growth and angiogenesis. The combination of low dose
      chemotherapy and antiangiogenesis inhibitors suppresses growth of experimental
      tumours more effectively than conventional therapy. The effect of this
      combination on ovarian cancer remains to be evaluated. Therefore, we investigated
      the synergism of ginsenoside Rg3 and cyclophosphamide (CTX) on growth and
      angiogenesis of human ovarian cancer. METHODS: Twenty-eight female athymic mice
      were divided randomly into 4 groups of 7: ginsenoside Rg3, CTX, ginsenoside Rg3
      and CTX combination and control, after being transplanted with ovarian cancer
      cells (SKOV-3). The mice were given intraperitoneal injection of ginsenoside Rg3
      and CTX for the 10 days following inoculation of SKOV-3 cells. The life quality
      and number of living days of mice were recorded. The size of tumour, tumour
      inhibitive rate, life elongation rate, proliferating cell nuclear antigen
      labelling index (PCNALI), expression of vascular endothelial cell growth factor
      (VEGF) and microvessel density (MVD) of the tumour tissues were estimated.
      RESULTS: Life quality of mice in ginsenoside Rg3 and combined treatment groups
      were better and number of living days longer than control. Average tumour weights
      of each treated group were less than control and there was no significant
      difference among the treated groups. PCNALI of treated groups was lower than
      control. The MVD value and VEGF expression in treated groups were significantly
      lower than control and the MVD values of ginsenoside Rg3 and combined treatment
      groups were lower than that of CTX group. CONCLUSIONS: Ginsenoside Rg3
      significantly inhibited growth and angiogenesis of ovarian cancer when used alone
      or combined with CTX. Ginsenoside Rg3 and CTX combination reinforced the
      antitumour effect each other and improved the living quality and survival time of
      mice with tumour.

PMID- 17442208
TI  - Establishment and characterization of two new human embryonic stem cell lines,
      SYSU-1 and SYSU-2.
AB  - BACKGROUND: Human embryonic stem cells can propagate indefinitely in vitro and
      are able to differentiate into derivatives of all three embryonic germ layers.
      The excitement surrounding human embryonic stem cells lies largely in their
      potential to produce specialized cells that can be used for transplant therapies.
      However, further investigation requires additional cell lines with varying
      genetic background. Therefore, efforts to derive and establish more human
      embryonic stem cell lines are highly warranted. METHODS: Surplus embryos
      (blastocysts) from donors were used to isolate the inner cell mass by
      immunosurgery. All cells were cultured continuously on irradiated murine
      embryonic fibroblasts feed layer and likely human embryonic stem cell colonies
      were subsequently characterized by cell surface marker staining, karyotyping and
      teratoma formation. RESULTS: Two human embryonic stem cell lines (SYSU-1 and SYSU
      2) were established from surplus embryos. The two lines express several
      pluripotency markers including alkaline phosphatase, SSEA-4, Tra-1-60, Oct-4,
      Nanog and Rex-1. They remain in undifferentiated state with normal karyotype
      after prolonged passages and can form embryoid bodies in vitro and teratoma in
      vivo. CONCLUSION: Two new human embryonic stem cell lines have been established
      from surplus embryos. They can be used to understand selfrenewal and
      differentiating mechanisms and provide more choices for regenerative medicine.

PMID- 17442209
TI  - Relationship between intravascular ultrasound imaging features of coronary
      plaques and soluble CD105 level in patients with coronary heart disease.

PMID- 17442210
TI  - Safety and feasibility of emergent percutaneous coronary intervention with the
      transradial access in patients with acute myocardial infarction.

PMID- 17442211
TI  - Lymphogranuloma venereum caused by Chlamydia trachomatis serovar L3: a case
      report.

PMID- 17442212
TI  - Optimized cardiac resynchronization therapy in patients with congestive heart
      failure.

PMID- 17442213
TI  - Carotid artery stenting in patients with coexistent carotid and coronary artery
      disease.

PMID- 17442214
TI  - Complication of interventional treatment: noncoronary sinus of Valsalva aneurysm
      ruptured into the right atrium.

PMID- 17442215
TI  - Rapid development of late stent malappositon and coronary aneurysm following
      implantation of a paclitaxel-eluting coronary stent.

PMID- 17442216
TI  - Renin inhibition: the next step in suppression of the renin-angiotensin system?

PMID- 17442217
TI  - Renal damage in primary aldosteronism: results of the PAPY study.

PMID- 17442218
TI  - New concepts in adrenal vein sampling for aldosterone in the diagnosis of primary
      aldosteronism.
AB  - Improved diagnostic techniques and adoption of a systematic and thorough
      diagnostic workup can lead to identification of the surgically correctable forms
      of primary aldosteronism (PA) far more frequently than expected. Adrenalectomy
      can provide long-term normalization of blood pressure and correction of PA in
      most patients with an aldosterone-producing adenoma. Forms needing surgical
      correction are generally held to be less common than forms requiring medical
      therapy; however, this can be a misconception arising from the lack of systematic
      use of adrenal vein sampling (AVS). Currently AVS still remains the "gold
      standard" for identifying unilateral causes of PA that are surgically curable.
      The criteria for selecting patients to undergo AVS, the technique for performing
      AVS, and the criteria for analyzing and interpreting its results are summarized
      here.

PMID- 17442219
TI  - The role of aldosterone in resistant hypertension: implications for pathogenesis
      and therapy.
AB  - Resistant hypertension constitutes an increasingly common medical disorder.
      Although the exact incidence is not precisely known, estimates derived from
      recent outcome studies emphasize that resistant hypertension is much more common
      than previously thought. A major advance in our understanding of its pathogenesis
      and management is the recent recognition of the importance of aldosterone excess
      or autonomy as an important mechanism for drug resistance in hypertension. Recent
      studies of the effects of aldosterone on vascular smooth muscle have delineated
      several extra-renal mechanisms whereby aldosterone produces hypertension
      primarily by its direct vasoconstrictor effects and by altering vascular
      compliance. Consequently, aldosterone blockade constitutes an effective
      intervention for treating resistant hypertension.

PMID- 17442220
TI  - The metabolic syndrome in primary aldosteronism.
AB  - Patients with hypertension have a high prevalence of concurrent metabolic
      abnormalities (eg, obesity, dyslipidemia, and hyperglycemia). Clustering of these
      risk factors, defined as the metabolic syndrome, is associated with a high
      cardiovascular risk profile. This review summarizes current knowledge about the
      prevalence and characteristics of the metabolic syndrome in primary
      aldosteronism, and discusses the possible pathophysiological link between
      aldosterone and individual components of the metabolic syndrome, other than
      hypertension. Impaired glucose metabolism due to insulin resistance appears to be
      the major contributor to metabolic dysfunction in primary aldosteronism.
      Experimental observations support the possibility that aldosterone could act
      directly on insulin receptor function. The potential proadipogenic role of
      aldosterone and its negative effect on insulin sensitivity through production of
      cytokines remains to be investigated. Higher rates of cardiovascular events
      reported in primary aldosteronism could be due in part to the increased
      prevalence of the metabolic syndrome in this disorder.

PMID- 17442221
TI  - Why are mineralocorticoid receptors so nonselective?
AB  - Mineralocorticoid receptors (MR) bind aldosterone, cortisol, and progesterone
      with equal high affinity. Attention has focused on the role of MR in epithelial
      fluid and electrolyte homeostasis; from a variety of studies, however, MR are
      largely constitutively occupied by cortisol, with aldosterone an evolutionary
      latecomer, and MR pressed into service in epithelia to respond selectively to
      aldosterone through the co-expression of 11beta hydroxysteroid dehydrogenase type
      2. The pathophysiologic--and to a lesser extent the physiologic--roles of
      constitutively cortisol-occupied MR in nonepithelial tissues (eg, cardiomyocytes,
      neurons) are beginning to be delineated; the implications of the maintained high
      affinity of MR for progesterone, and their possible role as primarily
      progesterone sensors in reproductive (and other) tissues, await exploration.

PMID- 17442222
TI  - Phosphodiesterase type V: a novel therapeutic target for hypertension.

PMID- 17442223
TI  - The role of angiotensin AT1 receptor-associated protein in renin-angiotensin
      system regulation and function.
AB  - We cloned a novel molecule, AT1 receptor-associated protein (ATRAP), which is
      expressed in many tissues but specifically interacts with the AT1 receptor
      carboxyl-terminal. In the kidney, ATRAP was broadly distributed along the renal
      tubules; salt intake modulated its expression. In cardiovascular cells,
      angiotensin II (Ang II) stimulation made ATRAP co-localized with AT1 receptor in
      cytoplasm; ATRAP overexpression decreased cell surface AT1 receptor. In
      downstream signaling pathways, ATRAP suppressed Ang II-induced phosphorylation of
      mitogen-activated protein kinase, activation of c-fos gene transcription, and
      enhancement of amino acid or bromodeoxyuridine incorporation in cardiovascular
      cells. Thus, cardiovascular ATRAP may promote AT1 receptor internalization and
      attenuate Ang II-mediated cardiovascular remodeling. We would expect ATRAP to
      become a new therapeutic target molecule to treat and prevent cardiovascular
      remodeling in hypertension.

PMID- 17442224
TI  - Agonist autoantibodies against the angiotensin AT1 receptor in renal and
      hypertensive disorders.
AB  - Previous studies demonstrated the significance of an agonistic angiotensin II
      receptor AT1 autoantibody (AT1-AA) in preeclampsia. Because of its ability to
      release calcium in vascular smooth muscle cells, stimulate reactive oxygen
      species, and initiate proinflammatory processes, this antibody was thought to be
      important in the etiology and pathogenesis of preeclampsia. Recent
      investigations, however, have broadened and refined the pathobiological relevance
      of this antibody and refuted its role as the primary cause for preeclampsia.
      Because AT1-AA has been linked to an impaired uteroplacental perfusion and has
      been detected in patients with renal allograft rejection, its occurrence and
      function seem to be wider and more complex. This review summarizes current
      knowledge about the generation, function, and clinical importance of AT1-AA.

PMID- 17442225
TI  - Functional renin receptors in renal mesangial cells.
AB  - Activation of the renin-angiotensin system (RAS) and generation of angiotensin II
      (Ang II) play a crucial role in fibrotic renal disease beyond this system's
      hemodynamic actions. Ang II blockade was a great therapeutic breakthrough for
      renal and cardiovascular diseases; however, this slows, but does not stop,
      disease progression. These limitations leave other molecules unopposed to sustain
      disease progression. One is renin, which is markedly elevated by Ang II blockade.
      Recently, a new renin receptor was cloned in renal mesangial cells. This receptor
      acts as a renin/prorenin cofactor on the cell surface, enhancing efficiency of
      angiotensinogen cleavage by renin and unmasking prorenin catalytic activity.
      Unexpectedly, the receptor induces angiotensin-independent cellular effects in
      renal mesangial cells, suggesting that renin has novel receptor-mediated actions
      that could play a role in renal fibrosis. Proof of this could lead to a
      pharmacological compound blocking renin/prorenin binding and activity as an
      alternative or adjunct to classical inhibitors of the RAS.

PMID- 17442226
TI  - Atherosclerotic renovascular disease and renal impairment: can we predict the
      effect of intervention?
AB  - Atherosclerotic renal artery stenosis (ARAS) is associated with hypertension,
      ischemic nephropathy, and high cardiovascular risk. We review the data on
      revascularization of the renal artery by percutaneous transluminal renal
      angioplasty (PTRA) and pharmacological therapy. In patients with severe ARAS and
      poorly controlled hypertension, PTRA can improve blood pressure control. In
      patients with rapid renal function loss and severe ARAS, PTRA can improve short
      term renal function, but there is no evidence for long-term renoprotection.
      Recent evidence indicates that ARAS, and incidental renal artery stenosis,
      considerably increases cardiovascular risk, independent of blood pressure, renal
      function, and prevalent risk factors. This suggests that revascularization might
      potentially improve overall prognosis, but no data are available currently. The
      high cardiovascular risk warrants aggressive pharmacological treatment to prevent
      progression of the generalized vascular disorder. Ongoing trials will show
      whether revascularization has added, long-term effects on blood pressure, renal
      function, and cardiovascular prognosis.

PMID- 17442227
TI  - In hypertension, the kidney rules.
AB  - The renin-angiotensin system (RAS) is a critical regulator of blood pressure and
      fluid homeostasis. Components of the RAS, including renin, angiotensin-converting
      enzyme (ACE), and angiotensin type 1 (AT1) receptors, are expressed throughout
      the body in tissues that may impact blood pressure control. Blocking actions of
      individual components of the RAS lowers blood pressure. Although it has been
      suggested that control of sodium excretion by the kidney is the dominant
      mechanism for blood pressure regulation by the RAS, pharmacologic antagonists or
      conventional gene targeting experiments globally interrupt the RAS and cannot
      discriminate its actions in the kidney from other tissue compartments. Recent
      experiments using kidney cross-transplantation and genetically engineered mice
      have confirmed a major role for angiotensin II acting via AT1 receptors in the
      kidney in hypertension. These actions of renal AT1 receptors are required for the
      development of angiotensin II-dependent hypertension and cardiac hypertrophy.
      These findings, with previous experiments, clearly establish the critical role of
      the kidney in the pathogenesis of hypertension and its cardiovascular
      complications.

PMID- 17442228
TI  - Non-pressure-related effects of dietary sodium.
AB  - After the demonstration of a positive correlation between sodium intake and
      arterial pressure in large population studies, the effect of short-term reduction
      in sodium intake demonstrated the efficacy of this nonpharmacological therapy. In
      addition, a positive relation between urinary sodium (the most reliable estimate
      of salt intake) and left ventricular hypertrophy was found; and in recent years
      it was shown that cardiovascular morbidity clearly progressed with increasing
      sodium intake, despite one contradictory study. The role of non-pressure-related
      effects of dietary sodium is discussed in order to bring more arguments for a
      large-scale attempt to reduce sodium intake by 30% to 50%.

PMID- 17442229
TI  - Does remission of renal disease associated with antihypertensive treatment exist?
AB  - In diabetic and nondiabetic chronic nephropathies, high blood pressure and
      urinary loss of proteins represent major determinants of progressive renal
      function decline. Reducing blood pressure with drugs that inhibit the renin
      angiotensin system also lowers glomerular hypertension and ameliorates glomerular
      sieving properties, thus reducing proteinuria. Reducing urinary protein levels
      with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor
      antagonists (ARA) limits renal function decline to the point that remission of
      disease and regression of renal lesions have been observed in experimental
      animals and in humans. This therapy, however, may not be effective in all
      patients. For patients who do not achieve complete remission of proteinuria,
      renoprotective treatment should include intensified blood pressure control (and
      metabolic control in diabetes) and amelioration of dyslipidemia. Early
      intervention, before progressive glomerulosclerosis and scarring is initiated by
      increased protein traffic, may be important to maximize reno- and
      cardioprotection, especially in diabetes.

PMID- 17442230
TI  - Soft tissue sarcoma.

PMID- 17442231
TI  - Treatment of advanced soft tissue sarcoma: conventional agents and promising new
      drugs.
AB  - Effective treatment of advanced soft tissue sarcomas remains challenging, despite
      more than 30 years of clinical trials with conventional chemotherapy. Although
      some agents display modest efficacy against soft tissue sarcomas, modifications
      in the doses and combinations of therapies have not consistently led to
      significant improvements in response rates or concomitant increase in overall
      survival. Novel therapies designed to inhibit defined molecular alterations, as
      exemplified by the use of imatinib in gastrointestinal stromal tumors, have
      revolutionized the approach to the treatment of sarcomas. As more underlying
      genetic mechanisms are uncovered, new agents designed to target these lesions
      will lead to more specific, less toxic, and more effective therapies.

PMID- 17442232
TI  - Pathology of soft tissue sarcoma.
AB  - The evaluation and treatment of soft tissue sarcomas has never been more
      demanding than it is today. The pathologist plays a central role in this process
      and is an integral member of the multidisciplinary sarcoma treatment team. This
      article provides a brief summary of the role of the soft tissue pathologist and
      includes sections on methods of diagnosis, frozen section, classification of
      sarcomas, expert consultation, molecular pathology, grading, assessment of
      treatment response, and tumor banking.

PMID- 17442233
TI  - Bone cancer.

PMID- 17442234
TI  - Imaging of bone sarcomas.
AB  - Identification, staging, and treatment of bone sarcomas rely on both clinical and
      imaging evaluations. Although conventional radiography remains the primary
      imaging modality for characterizing bone tumors, bone scintigraphy, computed
      tomography, magnetic resonance imaging, and positron emission tomography can each
      add information for staging and treatment planning.

PMID- 17442235
TI  - Chemotherapy in the management of osteosarcoma and Ewing's sarcoma.
AB  - Sarcomas of bone are rare malignancies diagnosed in fewer than 3000 individuals
      yearly in the United States. Ewing's sarcoma and most osteosarcoma are high-grade
      neoplasms and account for approximately one half of bone sarcoma cases. Fewer
      than 20% of patients presenting with localized Ewing's sarcoma or osteosarcoma
      are cured with surgery alone. Current management typically involves collaboration
      among orthopedic oncologists, medical oncologists, musculoskeletal radiologists,
      sarcoma pathologists, and radiation oncologists. Modern multidisciplinary
      management of Ewing's sarcoma and osteosarcoma has improved the cure rate of
      patients with localized disease to more than 50%. Primary chemotherapy for high
      grade bone sarcomas often involves intensive, multiagent regimens, and few
      secondary chemotherapy options are available to treat refractory or relapsed
      disease. Patient participation in clinical trials of novel therapies for Ewing's
      sarcoma and osteosarcoma should be strongly encouraged.

PMID- 17442236
TI  - The role of radiation treatment in the contemporary management of bone tumors.
AB  - Radiotherapy is integral in the multidisciplinary approach to patients with
      musculoskeletal neoplasms. Multiple studies have established a role for
      radiotherapy as a definitive local treatment of unresectable lesions or when
      surgery might yield unacceptable functional outcomes, such as in Ewing's tumor or
      base of skull chondrosarcoma. Radiotherapy is also used as an adjuvant treatment
      after surgery with close or positive margins. In the metastatic setting, external
      beam radiotherapy and bone-seeking intravenous radioisotopes are used on a case
      by-case basis for palliation. As radiotherapy and its delivery techniques have
      evolved, so has its role in treating tumors such as Ewing's sarcoma, chordoma and
      chondrosarcoma, osteosarcoma, primary lymphoma of bone, malignant fibrous
      histiocytoma of bone, and vascular tumors. Radiation can also be successfully
      used to treat unresectable or recurrent benign tumors, such as giant cell tumor
      and aneurysmal bone cyst. This article reviews the indications for radiotherapy
      for various bone tumors and summarizes some of the important data supporting its
      use.

PMID- 17442237
TI  - PKC defends crown against Munc13.
AB  - Protein kinase C has long been thought to mediate DAG signaling at the synapse.
      Recently PKC has been supplanted by members of the Unc13 family as the
      predominant effectors of DAG signaling. Thanks to a study by Wierda and
      colleagues in this issue of Neuron, PKC returns to reclaim part of the kingdom:
      both pathways must be active to activate presynaptic potentiation.

PMID- 17442238
TI  - Representation of response categories in visual cortex.
AB  - It is known that single neurons in visual area V4 are selective for visual
      features and that their responses are modulated by selective attention.
      Surprisingly, a new study by Mirabella et al. in this issue of Neuron found that
      V4 neurons also signal the behavioral response category of the attended feature.

PMID- 17442239
TI  - Interoceptive basis to craving.
AB  - Awareness of one's physiology is an important component of emotion. How might
      these processes be related to addiction? In a recent issue of Science, Naqvi et
      al. demonstrated that smoking addiction is disrupted by damage to the insula
      cortex. This suggests that brain circuits mediating interoception also contribute
      to craving states.

PMID- 17442240
TI  - Switching gears: translational mastery of transcription during memory formation.
AB  - A critical molecular requirement underlying many forms of long-lasting synaptic
      plasticity and memory is the de novo synthesis of mRNAs and proteins. In a recent
      paper in Cell, Costa-Mattioli et al. present data from a pharmacogenetic study
      that places a key regulatory event in the "neural decision" to undergo these
      persistent neuronal changes under translational control mediated by eIF2alpha.

PMID- 17442241
TI  - Response to: Kim et al., "axon regeneration in young adult mice lacking Nogo
      A/B." Neuron 38, 187-199.

PMID- 17442242
TI  - Response to correspondence: Kim et al., "axon regeneration in young adult mice
      lacking Nogo-A/B." Neuron 38, 187-199.

PMID- 17442243
TI  - In vivo light-induced activation of neural circuitry in transgenic mice
      expressing channelrhodopsin-2.
AB  - Channelrhodopsin-2 (ChR2) is a light-gated, cation-selective ion channel isolated
      from the green algae Chlamydomonas reinhardtii. Here, we report the generation of
      transgenic mice that express a ChR2-YFP fusion protein in the CNS for in vivo
      activation and mapping of neural circuits. Using focal illumination of the
      cerebral cortex and olfactory bulb, we demonstrate a highly reproducible, light
      dependent activation of neurons and precise control of firing frequency in vivo.
      To test the feasibility of mapping neural circuits, we exploited the circuitry
      formed between the olfactory bulb and the piriform cortex in anesthetized mice.
      In the olfactory bulb, individual mitral cells fired action potentials in
      response to light, and their firing rate was not influenced by costimulated
      glomeruli. However, in piriform cortex, the activity of target neurons increased
      as larger areas of the bulb were illuminated to recruit additional glomeruli.
      These results support a model of olfactory processing that is dependent upon
      mitral cell convergence and integration onto cortical cells. More broadly, these
      findings demonstrate a system for precise manipulation of neural activity in the
      intact mammalian brain with light and illustrate the use of ChR2 mice in
      exploring functional connectivity of complex neural circuits in vivo.

PMID- 17442244
TI  - neuroConstruct: a tool for modeling networks of neurons in 3D space.
AB  - Conductance-based neuronal network models can help us understand how synaptic and
      cellular mechanisms underlie brain function. However, these complex models are
      difficult to develop and are inaccessible to most neuroscientists. Moreover, even
      the most biologically realistic network models disregard many 3D anatomical
      features of the brain. Here, we describe a new software application,
      neuroConstruct, that facilitates the creation, visualization, and analysis of
      networks of multicompartmental neurons in 3D space. A graphical user interface
      allows model generation and modification without programming. Models within
      neuroConstruct are based on new simulator-independent NeuroML standards, allowing
      automatic generation of code for NEURON or GENESIS simulators. neuroConstruct was
      tested by reproducing published models and its simulator independence verified by
      comparing the same model on two simulators. We show how more anatomically
      realistic network models can be created and their properties compared with
      experimental measurements by extending a published 1D cerebellar granule cell
      layer model to 3D.

PMID- 17442245
TI  - Coordinated accumbal dopamine release and neural activity drive goal-directed
      behavior.
AB  - Intracranial self-stimulation (ICSS) activates the neural pathways that mediate
      reward, including dopaminergic terminal areas such as the nucleus accumbens
      (NAc). However, a direct role of dopamine in ICSS-mediated reward has been
      questioned. Here, simultaneous voltammetric and electrophysiological recordings
      from the same electrode reveal that, at certain sites, the onset of anticipatory
      dopamine surges and changes in neuronal firing patterns during ICSS are
      coincident, whereas sites lacking dopamine changes also lack patterned firing.
      Intrashell microinfusion of a D1, but not a D2 receptor antagonist, blocks ICSS.
      An iontophoresis approach was implemented to explore the effect of dopamine
      antagonists on firing patterns without altering behavior. Similar to the
      microinfusion experiments, ICSS-related firing is selectively attenuated
      following D1 receptor blockade. This work establishes a temporal link between
      anticipatory rises of dopamine and firing patterns in the NAc shell during ICSS
      and suggests that they may play a similar role with natural rewards and during
      drug self-administration.

PMID- 17442246
TI  - Control of CNS cell-fate decisions by SHP-2 and its dysregulation in Noonan
      syndrome.
AB  - Within the developing mammalian CNS, growth factors direct multipotent precursors
      to generate neurons versus glia, a process that if perturbed might lead to neural
      dysfunction. In this regard, genetic mutations resulting in constitutive
      activation of the protein tyrosine phosphatase SHP-2 cause Noonan Syndrome (NS),
      which is associated with learning disabilities and mental retardation. Here, we
      demonstrate that genetic knockdown of SHP-2 in cultured cortical precursors or in
      the embryonic cortex inhibited basal neurogenesis and caused enhanced and
      precocious astrocyte formation. Conversely, expression of an NS SHP-2 mutant
      promoted neurogenesis and inhibited astrogenesis. Neural cell-fate decisions were
      similarly perturbed in a mouse knockin model that phenocopies human NS. Thus, SHP
      2 instructs precursors to make neurons and not astrocytes during the neurogenic
      period, and perturbations in the relative ratios of these two cell types upon
      constitutive SHP-2 activation may contribute to the cognitive impairments in NS
      patients.

PMID- 17442247
TI  - Ivermectin Interaction with transmembrane helices reveals widespread
      rearrangements during opening of P2X receptor channels.
AB  - P2X receptors are trimeric cation channels that open in response to binding of
      extracellular ATP. Each subunit contains a large extracellular ligand binding
      domain and two flanking transmembrane (TM) helices that form the pore, but the
      extent of gating motions of the TM helices is unclear. We probed these motions
      using ivermectin (IVM), a macrocyclic lactone that stabilizes the open state of
      P2X(4) receptor channels. We find that IVM partitions into lipid membranes and
      that transfer of the TM regions of P2X(4) receptors is sufficient to convey
      sensitivity to the lactone, suggesting that IVM interacts most favorably with the
      open conformation of the two TM helices at the protein-lipid interface. Scanning
      mutagenesis of the two TMs identifies residues that change environment between
      closed and open states, and substitutions at a subset of these positions weaken
      IVM binding. The emerging patterns point to widespread rearrangements of the TM
      helices during opening of P2X receptor channels.

PMID- 17442248
TI  - Interdependence of PKC-dependent and PKC-independent pathways for presynaptic
      plasticity.
AB  - Diacylglycerol (DAG) is a prominent endogenous modulator of synaptic
      transmission. Recent studies proposed two apparently incompatible pathways, via
      protein kinase C (PKC) and via Munc13. Here we show how these two pathways
      converge. First, we confirm that DAG analogs indeed continue to potentiate
      transmission after PKC inhibition (the Munc13 pathway), but only in neurons that
      previously experienced DAG analogs, before PKC inhibition started. Second, we
      identify an essential PKC pathway by expressing a PKC-insensitive Munc18-1 mutant
      in munc18-1 null mutant neurons. This mutant supported basic transmission, but
      not DAG-induced potentiation and vesicle redistribution. Moreover, synaptic
      depression was increased, but not Ca2+-independent release evoked by hypertonic
      solutions. These data show that activation of both PKC-dependent and -independent
      pathways (via Munc13) are required for DAG-induced potentiation. Munc18-1 is an
      essential downstream target in the PKC pathway. This pathway is of general
      importance for presynaptic plasticity.

PMID- 17442250
TI  - Neurons in area V4 of the macaque translate attended visual features into
      behaviorally relevant categories.
AB  - Neural processing at most stages of the primate visual system is modulated by
      selective attention, such that behaviorally relevant information is emphasized at
      the expenses of irrelevant, potentially distracting information. The form of
      attention best understood at the cellular level is when stimuli at a given
      location in the visual field must be selected (space-based attention). In
      contrast, fewer single-unit recording studies have so far explored the cellular
      mechanisms of attention operating on individual stimulus features, specifically
      when one feature (e.g., color) of an object must guide behavioral responses while
      a second feature (e.g., shape) of the same object is potentially interfering and
      therefore must be ignored. Here we show that activity of neurons in macaque area
      V4 can underlie the selection of elemental object features and their
      "translation" into a categorical format that can directly contribute to the
      control of the animal's behavior.

PMID- 17442249
TI  - Coactivation of pre- and postsynaptic signaling mechanisms determines cell
      specific spike-timing-dependent plasticity.
AB  - Synapses may undergo long-term increases or decreases in synaptic strength
      dependent on critical differences in the timing between pre-and postsynaptic
      activity. Such spike-timing-dependent plasticity (STDP) follows rules that govern
      how patterns of neural activity induce changes in synaptic strength. Synaptic
      plasticity in the dorsal cochlear nucleus (DCN) follows Hebbian and anti-Hebbian
      patterns in a cell-specific manner. Here we show that these opposing responses to
      synaptic activity result from differential expression of two signaling pathways.
      Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling underlies Hebbian
      postsynaptic LTP in principal cells. By contrast, in interneurons, a temporally
      precise anti-Hebbian synaptic spike-timing rule results from the combined effects
      of postsynaptic CaMKII-dependent LTP and endocannabinoid-dependent presynaptic
      LTD. Cell specificity in the circuit arises from selective targeting of
      presynaptic CB1 receptors in different axonal terminals. Hence, pre- and
      postsynaptic sites of expression determine both the sign and timing requirements
      of long-term plasticity in interneurons.

PMID- 17442251
TI  - A neural circuit model of flexible sensorimotor mapping: learning and forgetting
      on multiple timescales.
AB  - Volitional behavior relies on the brain's ability to remap sensory flow to motor
      programs whenever demanded by a changed behavioral context. To investigate the
      circuit basis of such flexible behavior, we have developed a biophysically based
      decision-making network model of spiking neurons for arbitrary sensorimotor
      mapping. The model quantitatively reproduces behavioral and prefrontal single
      cell data from an experiment in which monkeys learn visuomotor associations that
      are reversed unpredictably from time to time. We show that when synaptic
      modifications occur on multiple timescales, the model behavior becomes flexible
      only when needed: slow components of learning usually dominate the decision
      process. However, if behavioral contexts change frequently enough, fast
      components of plasticity take over, and the behavior exhibits a quick forget-and
      learn pattern. This model prediction is confirmed by monkey data. Therefore, our
      work reveals a scenario for conditional associative learning that is distinct
      from instant switching between sets of well-established sensorimotor
      associations.

PMID- 17442252
TI  - Beyond the edges of a view: boundary extension in human scene-selective visual
      cortex.
AB  - To allow perception of a continuous world, cortical mechanisms extrapolate
      missing information with highly constrained predictions about the environment
      just beyond the edges of a view. Here, we report functional magnetic resonance
      imaging evidence for extrapolation of scene layout information beyond what was
      physically presented, an illusion known as boundary extension. Consistent with
      behavioral reports, we observed boundary extension for scene-selective
      attenuation in the parahippocampal place area (PPA) and retrosplenial cortex
      (RSC), but no such extrapolation of object representations in the lateral
      occipital complex (LOC). These results demonstrate that scene layout
      representations are extrapolated beyond the confines of the perceptual input.
      Such extrapolation may facilitate perception of a continuous world from
      discontinuous views.

PMID- 17442253
TI  - Detection of the abundance of diacylglycerol and triacylglycerol molecular
      species in cells using neutral loss mass spectrometry.
AB  - Triacylglycerols (TAGs) are neutral lipids present in all mammalian cells as
      energy reserves, and diacylglycerols (DAGs) are present as intermediates in
      phospholipid biosynthesis and as signaling molecules. The molecular species of
      TAGs and DAGs present in mammalian cells are quite complex, and previous
      investigations revealed multiple isobaric species having molecular weights at
      virtually every even mass between 600 and 900 Da, making it difficult to assess
      changes of individual molecular species after cell activation. A method has been
      developed, using tandem MS and neutral loss scanning, to quantitatively analyze
      changes in those glyceryl ester molecular species containing identical fatty acyl
      groups. This was carried out by neutral loss scanning of 18 common fatty acyl
      groups where the neutral loss corresponded to the free carboxylic acid plus
      NH(3). Deuterium-labeled internal standards were used to normalize the signal for
      each nominal [M+NH(4)](+) ion undergoing this neutral loss reaction. This method
      was applied in studies of TAGs in RAW 264.7 cells treated with the toll-like
      receptor 4 ligand Kdo(2)-lipid A. A 50:1-TAG containing 18:1 was found to
      increase significantly over a 24-h time course after Kdo(2)-lipid A exposure,
      whereas an isobaric 50:1-TAG containing 16:1 did not change relative to controls.

PMID- 17442254
TI  - Capture of genomic DNA on glass microscope slides.
AB  - It is well known that DNA strands bind to silica surfaces in the presence of high
      concentrations of chaotropic salts. We developed simple methods to evaluate
      binding and recovery of DNA on flat glass microscope slides and compared their
      properties with commercially available silica "spin columns". Surprisingly,
      genomic DNA was recovered efficiently from untreated glass slides. Binding and
      elution times from glass slides were optimized in experiments with DNA samples of
      various sizes and defined buffers. Average DNA recovery from 500 ng of input
      genomic DNA varied from 25 to 53% for the glass slide protocol. Yields were
      comparable to those of spin columns. Human serum albumin and plasma components
      decreased DNA binding to glass several-fold in a concentration-dependent manner.
      These results support the concept of using flat glass slides as DNA purification
      surfaces in microfluidic devices for PCR sample preparation.

PMID- 17442255
TI  - Assessing the roles of essential functional groups in the mechanism of homoserine
      succinyltransferase.
AB  - Homoserine acyltransferases catalyze the commitment step to methionine and other
      important biological precursors which make this class of enzymes essential for
      the survival of bacteria, plants and fungi. This class of enzymes is not found in
      humans, making them an attractive new target for antimicrobial design. Homoserine
      O-succinyltransferase (HST) is a representative from this class, with little
      known about the key amino acids involved in substrate specificity and catalysis.
      HST from Escherichia coli has been cloned, purified and kinetically
      characterized. Through site-directed mutagenesis and steady-state kinetic studies
      the residues that comprise a catalytic triad for HST, the catalytic cysteine
      nucleophile, an active site acid-base histidine, and the base orienting
      glutamate, have been identified and characterized. Several residues which confer
      substrate specificity for both homoserine and succinyl-CoA have also been
      identified and kinetically evaluated. Mutations of an active site glutamate to
      either aspartate or alanine drastically increase the K(m) for homoserine,
      assigning this glutamate to a binding role for the alpha-amino group of
      homoserine. An active site arginine orients the carboxyl moiety of homoserine,
      while the carboxyl moiety of succinyl-CoA is positioned for catalysis by a lysine
      residue. Removing functionality at either of these positions alters the enzyme's
      ability to effectively utilize homoserine or succinyl-CoA, respectively,
      reflected in an increased K(m) and decreased catalytic efficiency. The data
      presented here provides new details of the catalytic mechanism of
      succinyltransferases, resolves a controversy between alternative mechanistic
      hypotheses, and provides a starting point for the development of selective
      inhibitors of HST.

PMID- 17442256
TI  - Cellular stress and intracellular zinc dyshomeostasis.
AB  - Various stressful conditions like oxidative or nitrosative stress, heavy metal
      load or thiol-modifying compounds have been shown to disturb the intracellular
      zinc homeostasis leading to increasing concentrations of free zinc within the
      cytoplasm or nuclei of cells. However, much less is known about the consequences
      of a disturbed intracellular Zn2+ homeostasis under these conditions. Current
      knowledge is reviewed here.

PMID- 17442257
TI  - Cobalamin-mediated regulation of transcobalamin receptor levels in rat organs.
AB  - Total gastrectomy (TG) causes cobalamin (Cbl) deficiency followed by increases in
      tumor necrosis factor (TNF)-alpha levels in the spinal cord (SC) of the rat. In
      order to understand how Cbl deficiency may influence cell Cbl transport, we have
      measured by immunoblotting protein levels of the receptor for the Cbl
      transcobalamin (TC) complex (TC-R) in both animal and cell models. TC-R protein
      levels were elevated in the total membranes of duodenal mucosa, kidneys, liver,
      and SC of rats made Cbl-deficient (Cbl-D) by means of TG or feeding with a Cbl-D
      diet. Postoperative Cbl-replacement treatment normalized the TC-R protein levels
      in each of the tested organs, regardless of whether this treatment was given
      during the first two post-TG or during the third and fourth post-TG mo. In Caco-2
      cells, progressively increasing TNF-alpha concentrations supplemented to culture
      medium induced an up-regulation of TC-R protein levels. We provide the first
      evidence of the regulation of a Cbl-specific receptor by the vitamin itself in
      some rat organs.

PMID- 17442258
TI  - Characterization of excess hard tissue occurring in the mesio-buccal surface of
      the mandibular first molar in microphthalmic mouse.
AB  - OBJECTIVE: The aim of the present study was to characterize the excess hard
      tissue on the mandible of the microphthalmic mouse having a mutation at the mitf
      locus. DESIGN: Homozygous mutant (mi/mi) and wild-type (+/+) mice were obtained
      by mating a breeding pair (strain name, B6C3Fe a/a-Mitf(mi)/J). We used mi/mi and
      +/+ mice at ages 6, 7, 8, 9, 28, and 49 days for micro-computed tomographic and
      histologic analyses. RESULTS: Excess hard tissue was found on the mesio-buccal
      surface of the mandibular first molar in all 11mi/mi mice, but none was found in
      the 8mi/+ or 14 +/+ mice. The excess hard tissue was located in the mental
      foramen connected to the mandibular canal. The mandibular canal passed near the
      basal part of the incisor and the root of the mandibular first molar due to
      aberrant development of the teeth and mandible. The excess hard tissue contained
      predentine immunostained for dentine sialoprotein, a marker for early stages of
      dentinogenesis, which was first observed at about 7 days of age. Dentine,
      predentine, pulp, and root-like structures were observed in the excess hard
      tissue, but neither enamel nor enamel organ was observed. CONCLUSION: Odontogenic
      cells in the basal part of the incisor and/or the mandibular first molar with the
      ability to develop into odontoblasts and pulp cells appeared to migrate through
      the mandibular canal to the mental foramen, where they developed into
      odontoblasts and pulp-like cells, and then formed dentine and predentine-like
      structures.

PMID- 17442259
TI  - Structure, function and regulation of plant photosystem I.
AB  - Photosystem I (PSI) is a multisubunit protein complex located in the thylakoid
      membranes of green plants and algae, where it initiates one of the first steps of
      solar energy conversion by light-driven electron transport. In this review, we
      discuss recent progress on several topics related to the functioning of the PSI
      complex, like the protein composition of the complex in the plant Arabidopsis
      thaliana, the function of these subunits and the mechanism by which nuclear
      encoded subunits can be inserted into or transported through the thylakoid
      membrane. Furthermore, the structure of the native PSI complex in several
      oxygenic photosynthetic organisms and the role of the chlorophylls and
      carotenoids in the antenna complexes in light harvesting and photoprotection are
      reviewed. The special role of the 'red' chlorophylls (chlorophyll molecules that
      absorb at longer wavelength than the primary electron donor P700) is assessed.
      The physiology and mechanism of the association of the major light-harvesting
      complex of photosystem II (LHCII) with PSI during short term adaptation to
      changes in light quality and quantity is discussed in functional and structural
      terms. The mechanism of excitation energy transfer between the chlorophylls and
      the mechanism of primary charge separation is outlined and discussed. Finally, a
      number of regulatory processes like acclimatory responses and retrograde
      signalling is reviewed with respect to function of the thylakoid membrane. We
      finish this review by shortly discussing the perspectives for future research on
      PSI.

PMID- 17442260
TI  - Eight steps preceding O-O bond formation in oxygenic photosynthesis--a basic
      reaction cycle of the Photosystem II manganese complex.
AB  - In oxygenic photosynthesis, water is split at a Mn(4)Ca complex bound to the
      proteins of photosystem II (PSII). Powered by four quanta of visible light, four
      electrons and four protons are removed from two water molecules before dioxygen
      is released. By this process, water becomes an inexhaustible source of the
      protons and electrons needed for primary biomass formation. On the basis of
      structural and spectroscopic data, we recently have introduced a basic reaction
      cycle of water oxidation which extends the classical S-state cycle [B. Kok, B.
      Forbush, M. McGloin, Cooperation of charges in photosynthetic O2 evolution- I. A
      linear four-step mechanism, Photochem. Photobiol. 11 (1970) 457-475] by taking
      into account also the role and sequence of deprotonation events [H. Dau, M.
      Haumann, Reaction cycle of photosynthetic water oxidation in plants and
      cyanobacteria, Science 312 (2006) 1471-1472]. We propose that the outwardly
      convoluted and irregular events of the classical S-state cycle are governed by a
      simple underlying principle: protons and electrons are removed strictly
      alternately from the Mn complex. Starting in I(0), eight successive steps of
      alternate proton and electron removal lead to I(8) and only then the O-O bond is
      formed. Thus not only four oxidizing equivalents, but also four bases are
      accumulated prior to the onset of dioxygen formation. After reviewing the kinetic
      properties of the individual S-state transition, we show that the proposed basic
      model explains a large body of experimental results straightforwardly.
      Furthermore we discuss how the I-cycle model addresses the redox-potential
      problem of PSII water oxidation and we propose that the accumulated bases
      facilitate dioxygen formation by acting as proton acceptors.

PMID- 17442261
TI  - Changes in photosynthetic electron transfer and state transitions in an herbicide
      resistant D1 mutant from soybean cell cultures.
AB  - Anomalies in photosynthetic activity of the soybean cell line STR7, carrying a
      single mutation (S268P) in the chloroplastic gene psbA that codes for the D1
      protein of the photosystem II, have been examined using different spectroscopic
      techniques. Thermoluminescence emission experiments have shown important
      differences between STR7 mutant and wild type cells. The afterglow band induced
      by both white light flashes and far-red continuous illumination was downshifted
      by about 4 degrees C and the Q band was upshifted by 5 degrees C. High
      temperature thermoluminescence measurements suggested a higher level of lipid
      peroxidation in mutant thylakoid membranes. In addition, the reduction rate of
      P700(+) was significantly accelerated in STR7 suggesting that the mutation led to
      an activation of the photosystem I cyclic electron flow. Modulated fluorescence
      measurements performed at room temperature as well as fluorescence emission
      spectra at 77 K revealed that the STR7 mutant is defective in state transitions.
      Here, we discuss the hypothesis that activation of the cyclic electron flow in
      STR7 cells may be a mechanism to compensate the reduced activity of photosystem
      II caused by the mutation. We also propose that the impaired state transitions in
      the STR7 cells may be due to alterations in thylakoid membrane properties induced
      by a low content of unsaturated lipids.

PMID- 17442262
TI  - The influence of hydrogen bonds on electron transfer rate in photosynthetic RCs.
AB  - Hydrogen bonds formed between photosynthetic reaction centers (RCs) and their
      cofactors were shown to affect the efficacy of electron transfer. The mechanism
      of such influence is determined by sensitivity of hydrogen bonds to electron
      density rearrangements, which alter hydrogen bonds potential energy surface.
      Quantum chemistry calculations were carried out on a system consisting of a
      primary quinone Q(A), non-heme Fe(2+) ion and neighboring residues(.) The primary
      quinone forms two hydrogen bonds with its environment, one of which was shown to
      be highly sensitive to the Q(A) state. In the case of the reduced primary quinone
      two stable hydrogen bond proton positions were shown to exist on [Q(A)-His(M219)]
      hydrogen bond line, while there is only one stable proton position in the case of
      the oxidized primary quinone. Taking into account this fact and also the ability
      of proton to transfer between potential energy wells along a hydrogen bond,
      theoretical study of temperature dependence of hydrogen bond polarization was
      carried out. Current theory was successfully applied to interpret dark P(+)/Q(A)(
      ) recombination rate temperature dependence.

PMID- 17442263
TI  - Heat- and light-induced reorganizations in the phycobilisome antenna of
      Synechocystis sp. PCC 6803. Thermo-optic effect.
AB  - By using absorption and fluorescence spectroscopy, we compared the effects of
      heat and light treatments on the phycobilisome (PBS) antenna of Synechocystis sp.
      PCC 6803 cells. Fluorescence emission spectra obtained upon exciting
      predominantly PBS, recorded at 25 degrees C and 77 K, revealed characteristic
      changes upon heat treatment of the cells. A 5-min incubation at 50 degrees C,
      which completely inactivated the activity of photosystem II, led to a small but
      statistically significant decrease in the F(680)/F(655) fluorescence intensity
      ratio. In contrast, heat treatment at 60 degrees C resulted in a much larger
      decrease in the same ratio and was accompanied by a blue-shift of the main PBS
      emission band at around 655 nm (F(655)), indicating an energetic decoupling of
      PBS from chlorophylls and reorganizations in its internal structure. (Upon
      exciting PBS, F(680) originates from photosystem II and from the terminal emitter
      of PBS.). Very similar changes were obtained upon exposing the cells to high
      light (600-7500 micromol photons m(-2) s(-1)) for different time periods (10 min
      to 3 h). In cells with heat-inactivated photosystem II, the variations caused by
      light treatment could clearly be assigned to a similar energetic decoupling of
      the PBS from the membrane and internal reorganizations as induced at around 60
      degrees C. These data can be explained within the frameworks of thermo-optic
      mechanism [Cseh et al. 2000, Biochemistry 39, 15250]: in high light the heat
      packages originating from dissipation might lead to elementary structural changes
      in the close vicinity of dissipation in heat-sensitive structural elements, e.g.
      around the site where PBS is anchored to the membrane. This, in turn, brings
      about a diminishment in the energy supply from PBS to the photosystems and
      reorganization in the molecular architecture of PBS.

PMID- 17442264
TI  - Role of hydrophobic residues in the voltage sensors of the voltage-gated sodium
      channel.
AB  - The role of hydrophobic residues in voltage sensors S4 of voltage-sensitive ion
      channels is less documented than that of charged residues. We performed alanine
      substitution of branched-sidechain residues contiguous to the third, fourth and
      fifth positively charged residues in S4s of the first three domains of the sodium
      channel expressed in HEK cells. These locations were selected because they are
      close to the arginines and lysines important in gating. Mutations in the first
      two domains (DIS4 and DIIS4) altered steady-state activation curves. In DIIIS4,
      the mutation L1131A next to the third arginine greatly slowed inactivation in a
      manner similar to that for substitutions of charged residues in DIVS4, whereas
      the mutation L1137A next to the fifth arginine preserved wild-type behaviour.
      Homology models of domain III, based on the structure of a crystallized mammalian
      potassium channel, shows that L1131 is located at the interface between S3 and S4
      helices, whereas L1137, on the opposite side of S4, does not interact with the
      voltage sensor. The two mutated residues are closer to each other in domains I
      and II than in domain III, as may be corroborated by their different
      electrophysiological effects.

PMID- 17442265
TI  - Office-based vs home-based behavioral treatment for obsessive-compulsive
      disorder: a preliminary study.
AB  - The current study investigated whether exposure with response prevention (ERP)
      for obsessive compulsive disorder (OCD) is more effective when administered in a
      participant's home or other natural environments where symptoms tend to occur,
      than in a therapist's office. Twenty-eight outpatients with a principal diagnosis
      of OCD were randomly assigned to receive ERP in their therapist's office vs.
      wherever their symptoms usually occur (e.g., at home, at work, in public places,
      in the car, etc.). Participants received 14, 90-min sessions of ERP with an
      individual therapist. Participants were assessed at pretreatment, post-treatment,
      and at 3- and 6-month follow-up. Assessments included both self-report as well as
      clinician-rated indicators of OCD symptom severity, depression, and functional
      impairment. Results suggested that participants improved significantly,
      regardless of where treatment occurred. There were no differences in efficacy
      between the home-based and office-based treatment for OCD. Implications of these
      findings are discussed.

PMID- 17442266
TI  - Fear conditioning in posttraumatic stress disorder: evidence for delayed
      extinction of autonomic, experiential, and behavioural responses.
AB  - Aversive conditioning has been proposed as an important factor involved in the
      etiology of posttraumatic stress disorder (PTSD). However, it is not yet fully
      understood exactly which learning mechanisms are characteristic for PTSD. PTSD
      patients (n=36), and healthy individuals with and without trauma exposure (TE
      group, n=21; nTE group, n=34), underwent a differential fear conditioning
      experiment consisting of habituation, acquisition, and extinction phases. An
      electrical stimulus served as the unconditioned stimulus (US), and two neutral
      pictures as conditioned stimuli (CS+, paired; CS-, unpaired). Conditioned
      responses were quantified by skin conductance responses (SCRs), subjective
      ratings of CS valence and US-expectancy, and a behavioural test. In contrast to
      the nTE group, PTSD patients showed delayed extinction of SCRs to the CS+. Online
      ratings of valence and US-expectancy as well as the behavioural test confirmed
      this pattern. These findings point to a deficit in extinction learning and
      highlight the role of affective valence appraisals and cognitive biases in PTSD.
      In addition, there was some evidence that a subgroup of PTSD patients had
      difficulties in learning the CS-US contingency, thereby providing preliminary
      evidence of reduced discrimination learning.

PMID- 17442267
TI  - The R1441C mutation of LRRK2 disrupts GTP hydrolysis.
AB  - Mutations in Leucine Rich Repeat Kinase 2 (LRRK2) are the leading genetic cause
      of Parkinson's disease (PD). LRRK2 is predicted to contain kinase and GTPase
      enzymatic domains, with recent evidence suggesting that the kinase activity of
      LRRK2 is central to the pathogenic process associated with this protein. The
      GTPase domain of LRRK2 plays an important role in the regulation of kinase
      activity. To investigate how the GTPase domain might be related to disease, we
      examined the GTP binding and hydrolysis properties of wild type and a mutant form
      of LRRK2. We show that LRRK2 immunoprecipitated from cells has a detectable
      GTPase activity that is disrupted by a familial mutation associated with PD
      located within the GTPase domain, R1441C.

PMID- 17442268
TI  - Deubiquitination of Chfr, a checkpoint protein, by USP7/HAUSP regulates its
      stability and activity.
AB  - Chfr, a mitotic stress checkpoint, plays an important role in cell cycle
      progression, tumor suppression and the processes that require the E3 ubiquitin
      ligase activity mediated by the RING finger domain. Chfr stimulates the formation
      of polyubiquitin chains by ub-conjugating enzymes, and induces the proteasome
      dependent degradation of a number of cellular proteins including Plk1 and Aurora
      A. In this study, we identified USP7 (also known as HAUSP), which is a member of
      a family of proteins that cleave polyubiquitin chains and/or ubiquitin
      precursors, as an interacting protein with Chfr by immunoaffinity purification
      and mass spectrometry, and their interaction greatly increases the stability of
      Chfr. In fact, USP7 can remove ubiquitin moiety from the autoubiquitinated Chfr
      both in vivo and in vitro, which results in the accumulation of Chfr in the cell.
      Thus, our finding suggests that USP7-mediated deubiquitination of Chfr leads to
      its accumulation, which might be a key regulatory step for Chfr activation and
      that USP7 may play an important role in the regulation of Chfr-mediated cellular
      processes including cell cycle progression and tumor suppression.

PMID- 17442269
TI  - Telomere-related functions of yeast KU in the repair of bleomycin-induced DNA
      damage.
AB  - Bleomycins are small glycopeptide cancer chemotherapeutics that give rise to 3'
      modified DNA double-strand breaks (DSBs). In Saccharomyces cerevisiae, DSBs are
      predominantly repaired by RAD52-dependent homologous recombination (HR) with some
      support by Yku70/Yku80 (KU)-dependent pathways. The main DSB repair function of
      KU is believed to be as part of the non-homologous end-joining (NHEJ) pathway,
      but KU also functions in a "chromosome healing" pathway that seals DSBs by de
      novo telomere addition. We report here that rad52Deltayku70Delta double mutants
      are considerably more bleomycin hypersensitive than rad52Deltalig4Delta cells
      that lack the NHEJ-specific DNA ligase 4. Moreover, the telomere-specific KU
      mutation yku80-135i also dramatically increases rad52Delta bleomycin
      hypersensitivity, almost to the level of rad52Deltayku80Delta. The results
      indicate that telomere-specific functions of KU play a more prominent role in the
      repair of bleomycin-induced damage than its NHEJ functions, which could have
      important clinical implications for bleomycin-based combination chemotherapies.

PMID- 17442270
TI  - The co-chaperone CHIP is induced in various stresses and confers protection to
      cells.
AB  - The C-terminus of Hsp70 interacting protein (CHIP) is being considered to be a
      cellular quality control E3 ubiquitin ligase because of its ability to degrade
      misfolded proteins in association with heat shock chaperones. The neuroprotective
      role of CHIP also has been implicated in several familial neurodegenerative
      diseases including polyglutamine diseases. However, the regulation of the
      expression of CHIP under different stress conditions and its protective role
      thereon is unknown. Here we have shown that the mRNA level of CHIP is
      significantly increased in the cells exposed to oxidative, endoplasmic reticulum
      and proteasomal stress. CHIP also protected from various stress-induced cell
      death. Finally, we have demonstrated upregulation of CHIP mRNA levels in the
      expanded polyglutamine protein expressing cells. Our result suggests that the
      upregulation of CHIP under various stress environments is an adaptive response of
      the cells to deal with the excess burden of misfolded protein.

PMID- 17442271
TI  - A catalytic approach to estimate the redox potential of heme-peroxidases.
AB  - The redox potential of heme-peroxidases varies according to a combination of
      structural components within the active site and its vicinities. For each
      peroxidase, this redox potential imposes a thermodynamic threshold to the range
      of oxidizable substrates. However, the instability of enzymatic intermediates
      during the catalytic cycle precludes the use of direct voltammetry to measure the
      redox potential of most peroxidases. Here we describe a novel approach to
      estimate the redox potential of peroxidases, which directly depends on the
      catalytic performance of the activated enzyme. Selected p-substituted phenols are
      used as substrates for the estimations. The results obtained with this catalytic
      approach correlate well with the oxidative capacity predicted by the redox
      potential of the Fe(III)/Fe(II) couple.

PMID- 17442272
TI  - Wnt-signaling is maintained and adipogenesis inhibited by TNFalpha but not MCP-1
      and resistin.
AB  - Type 2 diabetes and obesity with enlarged fat cells are associated with low-grade
      systemic inflammation, impaired adipogenesis as well as the recruitment of
      inflammatory cells into the adipose tissue. Cytokines like TNFalpha and IL-6 are
      secreted by the inflammatory cells and have been shown to impair normal adipocyte
      differentiation. An important mechanism whereby these cytokines inhibit
      adipogenesis is by maintaining an active Wnt-signaling pathway. Also other
      cytokines like MCP-1 and resistin are involved in the inflammatory process and
      are secreted by macrophages. If these cytokines also affect Wnt-signaling and
      adipocyte differentiation is currently unclear. In the present study, we show
      that while TNFalpha is able to maintain an active Wnt-signaling, induce
      inflammation and completely block adipose cell differentiation, no effect was
      found by either MCP-1 or resistin on these processes. Addition of the
      thiazolidinedione, pioglitazone, was found to antagonize the effect of TNFalpha
      on the Wnt-signaling process and, consequently, promote adipogenesis.

PMID- 17442273
TI  - Beta-oxidation in hepatocyte cultures from mice with peroxisomal gene knockouts.
AB  - Beta-oxidation of carboxylates takes place both in mitochondria and peroxisomes
      and in each pathway parallel enzymes exist for each conversion step. In order to
      better define the substrate specificities of these enzymes and in particular the
      elusive role of peroxisomal MFP-1, hepatocyte cultures from mice with peroxisomal
      gene knockouts were used to assess the consequences on substrate degradation.
      Hepatocytes from mice with liver selective elimination of peroxisomes displayed
      severely impaired oxidation of 2-methylhexadecanoic acid, the bile acid
      intermediate trihydroxycholestanoic acid (THCA), and tetradecanedioic acid. In
      contrast, mitochondrial beta-oxidation rates of palmitate were doubled, despite
      the severely affected inner mitochondrial membrane. As expected, beta-oxidation
      of the branched chain compounds 2-methylhexadecanoic acid and THCA was reduced in
      hepatocytes from mice with inactivation of MFP-2. More surprisingly, dicarboxylic
      fatty acid oxidation was impaired in MFP-1 but not in MFP-2 knockout hepatocytes,
      indicating that MFP-1 might play more than an obsolete role in peroxisomal beta
      oxidation.

PMID- 17442274
TI  - Cleavage of focal adhesion kinase (FAK) is essential in adipocyte
      differentiation.
AB  - During adipocyte differentiation, the cells experience dramatic alterations in
      morphology, motility and cell-ECM contact. Focal adhesion kinase (pp125FAK), a
      widely expressed non-receptor tyrosine kinase in integrin signaling, has been
      reported to participate in these events in various cells. Utilizing 3T3-L1 cells
      and primary rat preadipocytes, we explored the role of FAK in adipocyte
      differentiation. Gradual cleavage of FAK was demonstrated during adipcoyte
      differentiation, both in vitro and in vivo. This cleavage of FAK was mediated by
      calpain. Inhibition of calpain activity resulted in the rescue of FAK
      degradation, accompanied with the disturbance of final maturation of adipocyte.
      Our study revealed that FAK participated in adipocyte differentiation, and its
      cleavage by calpain was required to fulfill the final maturation of adipocytes.

PMID- 17442275
TI  - Aptamer from whole-bacterium SELEX as new therapeutic reagent against virulent
      Mycobacterium tuberculosis.
AB  - Worldwide, tuberculosis (TB) remains the most frequent and important infectious
      disease causing morbidity and death. One-third of the world's population is
      infected with Mycobacterium tuberculosis (MTB), the etiologic agent of TB.
      Because of the global health problems of TB, the development of potent new anti
      TB drugs without cross-resistance with known antimycobacterial agents is urgently
      needed. In this study, we have applied a Systematic Evolution of Ligands by
      Exponential Enrichment (SELEX) process to identify a single aptamer (NK2) that
      binds to virulent strain M. tuberculosis (H37Rv) with high affinity and
      specificity. We have found that this aptamer improves CD4(+)T cells to produce
      IFN-gamma after binding to H37Rv. The different component between H37Rv and BCG
      was identified as some membrane protein. Moreover, the survival rates of mice
      challenged with i.v. H37Rv have been prolonged after treatment with single
      injection of aptamer NK2. The bacterial numbers were significantly lower in the
      spleen of mice treated with aptamer NK2. The histopathological examination of
      lung biopsy specimens showed lesser pulmonary alveolar fusion and swelling in the
      presence of the aptamer. These results suggest that aptamer NK2 has inhibitory
      effects on M. tuberculosis and can be used as antimycobacterial agent.

PMID- 17442276
TI  - Low molecular weight chitosan is an efficient inhibitor of ribonucleases.
AB  - RNase inhibitors are commonly used to block the RNase activity in manipulations
      with RNA-containing preparations. Recently RNase inhibitors, either synthetic or
      natural, have been intensively sought because they appeared to be promising for
      therapy of cancer and allergy. However, there is only a limited number of
      efficient RNase inhibitors. We have shown that a low molecular weight chitosan
      (M(r) approximately 6 kDa) inhibits activity of pancreatic RNase A and some
      bacterial RNases with inhibition constants in the range of 30-220 nM at pH 7.0
      and ionic strength 0.14 M. The preferential contribution to the chitosan complex
      formation with RNases is due to establishment of 5-6 ion pairs. The results of
      this work show that polycations may efficiently inhibit ribonuclease activities.

PMID- 17442277
TI  - Benzo[a]pyrene-3,6-dione inhibited VEGF expression through inducing HIF-1alpha
      degradation.
AB  - Vascular endothelial growth factor (VEGF) is a potent angiogenesis inducer for
      tumor growth and angiogenesis. Benzo[a]pyrene (BaP) belongs to polycyclic
      aromatic hydrocarbons (PAHs) and is known to cause carcinogenesis. But the
      effects of BaP and its metabolites on VEGF and HIF-1 expression remain to be
      elucidated. In this study, we found benzo[a]pyrene-3,6-dione (BPQ), but not BaP
      and benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) inhibited VEGF expression in a
      dose-dependent manner. BPQ inhibited VEGF transcriptional activation through
      hypoxia-inducible factor 1 (HIF-1) binding site. BPQ specifically decreased HIF
      1alpha, but not HIF-1beta subunit expression in A549 cells. We found that BPQ did
      not inhibit HIF-1alpha mRNA level, but inhibited its protein expression in a
      proteasome-dependent manner. To further clarify the mechanism of BPQ in
      regulating HIF-1alpha stability, we found that BPQ inhibited HIF-1alpha protein
      expression by the increase of the proteasome-dependent degradation, and by the
      disruption of HIF-1alpha and Hsp90 association.

PMID- 17442278
TI  - Pseudoneglect and neglect for mental alphabet lines.
AB  - While patients with right parietal damage neglect the left side of stimuli, the
      intact-brain population shows a slight neglect of the right side--known as
      pseudoneglect. Although pseudoneglect occurs for physical stimuli, it is not
      certain whether the bias extends to mental representations. To investigate this
      issue, we examined spatial distortions in the representation of length for mental
      alphabet lines, which are thought to have a left-to-right arrangement. In Expt.
      1, participants (n=10) were presented with letter strings (e.g. C_H_P) and
      estimated whether the letter length was greater on the left or right side of the
      inner-letter. The strings were presented simultaneously along a line or
      sequentially in the centre of the screen in either an ascending (i.e. A-Z) or
      descending (i.e. Z-A) sequence. Participants reliably overestimated the length on
      the left regardless of presentation mode. In Expt. 2, participants (n=20) judged
      whether the inner-letter was the true centre. Responses were biased such that
      inner-letters shifted to the left of true centre were perceived to be the centre.
      Combined, both studies demonstrate that the length on left side of the mental
      alphabet line is overestimated relative to the right. In Expt. 3, a reversal of
      the bias towards the right was found for a group of neglect patients. The data
      demonstrate that letters have a left-to-right mental representation and that the
      left side of this representation is overrepresented in a manner similar to the
      overestimation associated with pseudoneglect for physical stimuli.

PMID- 17442279
TI  - Spontaneous recovery of a conditioned taste aversion differentially alters
      extinction-induced changes in c-Fos protein expression in rat amygdala and
      neocortex.
AB  - Conditioned taste aversions (CTAs) may be acquired when an animal consumes a
      novel taste (conditioned stimulus; CS) and then experiences the symptoms of
      poisoning (unconditioned stimulus; US). Animals will later avoid the taste that
      was previously associated with malaise. Extinction of a CTA is observed following
      repeated, non-reinforced exposures to the CS and represents itself as a
      resumption of eating/drinking the once-avoided tastant. Spontaneous recovery (SR)
      of a CTA (a revival of the taste avoidance) occurs when the CS is offered after a
      latency period in which the CS was not presented. An initial study explored the
      experimental parameters required to produce a reliable SR following acquisition
      and extinction of a robust CTA in rats. A CTA was formed through 3 pairings of
      0.3% oral saccharin (SAC) and 81 mg/kg i.p. lithium chloride (LiCl) followed by
      extinction training resulting in 90% reacceptance of SAC. After extinction
      training, some of the animals were also tested for SR of the CTA upon exposure to
      SAC following a 15-, 30-, or 60-day latency period of water drinking. We report
      here that latencies of 15, 30, or 60 days produced small, but reliable, SRs of
      the CTA--with longer latencies producing progressively more suppression of SAC
      consumption. A second study investigated changes in the amygdala (AMY), gustatory
      neocortex (GNC), and medial prefrontal cortex (mPFC) functioning during SR of a
      CTA. Using immunohistochemical methods, brain c-Fos protein expression was
      analyzed in rats that extinguished the CTA as well as those that exhibited SR of
      the CTA after a 30-day latency. Our previous studies indicated that the numbers
      of c-Fos-labeled neurons in GNC and mPFC is low following CTA acquisition and
      increase dramatically as rats fully extinguished the aversion. Here we report
      that cortical c-Fos protein expression declines significantly following SR of the
      CTA. Expression of c-Fos in basolateral AMY decreased significantly from EXT to
      SR, but control animals with an intact CTA also decreased significantly from a
      short-term CTA test to a long-term CTA test. Low levels of c-Fos expression in
      the central nucleus of the amygdala (CE) were observed throughout EXT with little
      change in expression detectable following SR. These measurements reflect the
      dynamic nature of brain activity during acquisition and extinction of a CTA and
      highlight an important role for cortical neurons in the brain reorganization that
      occurs during SR of a CTA. The data also suggest that certain sub-nuclei of the
      AMY may play a relatively minor role in SR of this defensive reaction to a
      learned fear.

PMID- 17442280
TI  - Structural characterization and immunological activity of two cold-water
      extractable polysaccharides from Cistanche deserticola Y. C. Ma.
AB  - Two major polysaccharide fractions, CDA-1A and CDA-3B, were isolated from the
      cold-water extract of Cistanche deserticola Y. C. Ma, a holoparasitic plant and a
      valuable traditional Chinese medicine, using anion-exchange chromatography on
      DEAE-cellulose and gel-permeation chromatography on Sephacryl S-300 and Sephadex
      G-150. Their major structural features were elucidated using component and
      linkage analyses, periodate oxidation, Smith degradation, partial acid
      hydrolysis, and NMR spectroscopy. The results indicated that CDA-1A is an alpha
      (1-->4)-D-glucan with alpha-(1-->6)-linked branches attached to the O-6 of branch
      points and that CDA-3B is an RG-I polysaccharide containing a typical
      rhamnogalacturonan backbone and arabinogalactan or arabinan branches. Bioactivity
      tests showed that CDA-1A is inert for T-cell proliferation stimulation but active
      for B-cell proliferation, while CDA-3B is potent for the stimulation of both T-
      and B-cell proliferation.

PMID- 17442281
TI  - Iminoalditol-amino acid hybrids: synthesis and evaluation as glycosidase
      inhibitors.
AB  - Cyclization by double reductive amination of D-xylo-hexos-5-ulose with the
      terminal amino group of alpha-N-Boc-lysine methyl ester gave a 4:1-mixture of
      (1'R)-N-methoxycarbonyl-(1-N-Boc-amino)pentyl-1-deoxynojirimycin and the
      corresponding L-ido epimer whereas D-lyxo-hexos-5-ulose furnished the desired N
      alkylated 1-deoxymannojirimycin derivative without any observable epimer
      formation at C-5. By subsequent modification of the lysine moiety, additional
      chain-extended derivatives as well as fluorescent compounds were obtained. All
      fluorescent iminoalditol-amino acid hybrids prepared in this study exhibited
      glycosidase inhibitory activities better than or comparable to the parent
      compounds'.

PMID- 17442282
TI  - The Na+/K+-ATPase alpha2-isoform regulates cardiac contractility in rat
      cardiomyocytes.
AB  - OBJECTIVE: The presence of both alpha1- and alpha2-isoforms of the Na+/K+-ATPase
      (NKA) in cardiomyocytes indicates different functions. We hypothesized that
      preferential localization of the alpha2-isoform to the t-tubules, locally
      controlling the Na+/Ca2+-exchanger (NCX), underlies a specific role in Ca2+
      handling. METHODS: We studied NKA isoform distribution in isolated cardiomyocytes
      from Wistar rats using immunocytochemistry. NKA pump and NCX currents (I(pump)
      and I(NCX)) were measured in control and detubulated cardiomyocytes.
      Intracellular Na+ concentration [Na+]i was assessed with the fluorescent dye
      SBFI. RESULTS: The alpha2-isoform abundance was higher in the t-tubules than in
      the surface sarcolemma. We established that 0.3 microM ouabain specifically
      blocked the alpha2-isoform in isolated rat cardiomyocytes. This low concentration
      blocked 10.7+/-0.6% of I(pump) in control, but only 6.0+/-0.5% in detubulated
      cardiomyocytes. Moreover, measured and calculated alpha1-specific and alpha2
      specific I(pump) in control (547+/-29 pA and 66 pA, respectively) and in
      detubulated cells (495+/-30 pA and 31 pA, respectively) showed that 53% of the
      alpha2-isoform, but only 9.5% of the alpha1-isoform, were localized to the t
      tubules. Despite the small abundance of the alpha2-isoform (approximately 11% of
      total NKA), selective inhibition of this isoform induced a 40% increase in
      contractility in field stimulated cardiomyocytes, but no increase in global
      [Na+]i. However, inhibition of the alpha2-isoform increased I(NCX) indicating
      local subsarcolemmal accumulation of Na+ near NCX. CONCLUSIONS: The alpha2
      isoform of the NKA is functionally coupled to the NCX and can regulate Ca2+
      handling without changing global [Na+]i.

PMID- 17442283
TI  - CD36 and macrophages in atherosclerosis.
AB  - CD36 is a multi-ligand scavenger receptor present on the surface of a number of
      cells such as platelets, monocytes/macrophages, endothelial and smooth muscle
      cells. Monocyte/macrophage CD36 has been shown to play a critical role in the
      development of atherosclerotic lesions by its capacity to bind and endocytose
      oxidized low density lipoproteins (OxLDL), and it is implicated in the formation
      of foam cells. However, the significance of CD36 in atherosclerosis has recently
      been called into question by different studies, and therefore its exact role
      still needs to be clarified. The aim of this article is to carefully review the
      importance of CD36 as an essential component in the pathogenesis of
      atherosclerosis.

PMID- 17442284
TI  - Transgenic overexpression of the secreted, extracellular EGF-CUB domain
      containing protein SCUBE3 induces cardiac hypertrophy in mice.
AB  - OBJECTIVE: The aim of this study was to investigate in a transgenic animal model
      the cardiac expression and function of a novel extracellular protein SCUBE3
      [signal peptide-CUB (complement proteins C1r/C1s, Uegf, and Bmp1)-EGF (epidermal
      growth factor)-like domain-containing protein 3]. METHODS AND RESULTS: Real-time
      quantitative reverse transcriptase (RT)-PCR analysis showed that SCUBE3 is
      expressed in the ventricular myocardium. Male transgenic (TG) mice overexpressing
      SCUBE3 appeared normal during development, from birth to adulthood. However,
      echocardiography and histopathological examination revealed significant cardiac
      hypertrophy in TG animals as they aged, at 8 months. Interestingly, left
      ventricle hypertrophy occurred more rapidly and more severely under pressure
      overload in TG mice, as compared to age-matched wild-type littermates. Induced
      SCUBE3 expression, together with elevated transforming growth factor (TGF)-beta1
      level under pressure overload, may account for the accelerated onset and
      progression of cardiac hypertrophy in TG mice. Furthermore, biochemical and
      molecular studies revealed that the carboxyl-terminal portion of SCUBE3 could
      physically interact with TGF-beta1 and promote the TGF-beta1-mediated
      transcriptional activation. CONCLUSION: This report is the first demonstration
      that SCUBE3 may play a role in the regulation of cardiac growth and remodeling
      responses, possibly through the stabilization of the TGF-beta1 signaling pathway.

PMID- 17442285
TI  - Information integration of protein-protein interactions as essential tools for
      immunomics.
AB  - After a brief introduction to point out the necessity to advance for a global
      understanding of the macromolecular interactions occurring during the immune
      system development and responses, Section 2 will be devoted to analyse the
      current tools for an automatic location of information on these protein-protein
      interactions in the web. In the next section (Section 3), we will point out
      different action lines to improve these tools and, consequently, to increase the
      efficiency to establish (to understand) the "protein network skeleton" that
      controls our immune responses. Finally, we will briefly present our current
      strategy and work to advance towards this goal.

PMID- 17442286
TI  - Analysis of vaccine's schedules using models.
AB  - We present a further, yet important, step in applying Catania Mouse Model &
      simulator (SimTriplex) of immune system response to vaccination. In particular we
      show that, as immune response can induce toxicity, one can calibrate the vaccine
      administrations in such a way to avoid toxicity effects, keeping immunoprevention
      from cancer. This result increases the model's potential applications.

PMID- 17442287
TI  - Mathematical modelling of liver regeneration after intoxication with CCl(4).
AB  - Liver regeneration is a complex process, having evolved to protect animals from
      the consequences of liver loss caused by food toxins. In this study, we
      established a mathematical spatial-temporal model of the liver lobule
      regenerating after CCl(4) intoxication. The aim of modelling the regeneration
      process by matching experimental observations with those from a mathematical
      model is to gain a better understanding of the process and to recognize which
      parameters are relevant for specific phenomena. In order to set up a realistic
      minimal model, we first reconstructed a schematised liver lobule after
      determination of: (i) the mean number of hepatocytes between the central vein and
      the periphery of the lobule, (ii) the mean size of the hepatocytes and (iii) the
      mean number of hepatocyte columns in the inner, midzonal and peripheral ring of
      the lobule. In a next step, we determined the time course of cell death and BrdU
      incorporation after intoxication of male Sprague Dawley rats with CCl(4), thereby
      differentiating between inner, midzonal and peripheral hepatocytes. These
      parameters were used to construct a model. The basic unit of this model is the
      individual cell. The detailed behaviour of the cells is studied, controlled by
      the model parameters: (1) probability of cell division at defined positions of
      the lobule at a given time, (2) "coordinated cell orientation", i.e., the ability
      of the cells to align during the regeneration process into columns towards the
      central vein of a liver lobule, (3) cell cycle duration, (4) the migration
      activity and (5) the polarity of the hepatocytes resulting in polar cell-cell
      adhesion between them. In a schematised lobule, the model shows that CCl(4)
      initially induced cell death of a pericentral ring of hepatocytes, followed by a
      wave of proliferation that starts in the surviving hepatocytes next to the inner
      ring of dead cells and continues to the peripheral hepatocytes, finally restoring
      the characteristic micro-architecture of the lobule in a 7-day process. This
      model was used to systematically analyze the influence of parameters 1-5.
      Interestingly, coordinated cell orientation and cell polarity were identified to
      be the most critical parameters. Elimination led to destruction of the
      characteristic micro-architecture of the lobule and to a high degree of disorder
      characterized by hexagonal cell structures. Our model suggests that the ability
      of hepatocytes to realign after cell division by a process of coordinated cell
      orientation (model parameter 2) in combination with cell polarity (model
      parameter 5) may be at least as critical as hepatocyte proliferation (model
      parameter 1) itself.

PMID- 17442288
TI  - Arbutin blocks defects in the ripple phase of DMPC bilayers by changing carbonyl
      organization.
AB  - The effect of arbutin, a 4-hydroxyphenyl-beta-glucopyranoside, on
      dimyristoylphosphatidylcholine (DMPC) bilayers was studied by turbidimetry, EPR
      and FTIR spectroscopies. The disruption of DMPC multilamellar vesicles (MLV's)
      with monomyristoylphosphatidylcholine (lysoPC), a product of hydrolysis of
      phospholipase A(2) (PLA(2)), is more efficient at 18 degrees C, where DMPC MLV's
      are known to be in the ripple P(beta') phase, than at 10 degrees C (L(beta') flat
      gel phase). Disruption at 18 degrees C was inhibited by increasing concentrations
      of arbutin in the solution. This inhibition was correlated with the disappearance
      of the ripple phase in MLV's when arbutin is present. Shifts in FTIR carbonyl
      bands caused by arbutin or by temperature changes allow us to propose a model. It
      is interpreted that the changes in the water-hydrocarbon interface caused by
      arbutin, forcing a reaccommodation of the carbonyl groups, eliminate the
      topological defects in the lattice due to mismatches among regions with different
      area per lipid where lysoPC can insert.

PMID- 17442289
TI  - Association of CYP2E1 and NAT2 gene polymorphisms with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Detoxification genes are potential candidates in the susceptibility
      of patients with chronic obstructive pulmonary disease. Polymorphisms in these
      genes alter the metabolism of xenobiotics such as present in cigarette smoke.
      METHODS: We conducted a case-control study to investigate total 9 polymorphisms
      of CYP2E1, CYP2D6 and NAT2 genes by PCR-RFLP. RESULTS: The -1053C/T and -1293G/C
      promoter polymorphisms of CYP2E1 were found to be in complete linkage
      disequilibrium (LD) (D'=1.00, r(2)=1.0, p<0.0001), whereas -1293G/C and 7632T/A
      polymorphisms of the same gene were also in significant LD (D'=0.5183, r(2)=1.0,
      p=0.01) in patients. The patients over-represented the -1293GC+CC genotypes of 
      1293G/C polymorphism of CYP2E1 (p=0.03) and NAT2*4/7, NAT2()5/6, NAT2*5/7,
      NAT2*6/6 and NAT2*6/7 genotypes of NAT2 (p=0.01, p=0.039, p=0.01, p=0.032,
      p=0.006, respectively), resulting in to higher frequency of -1293C (OR=7.02, 95%
      CI=1.63-30.15, p=0.002), NAT2*6 (OR=1.90, 95% CI=1.27-2.83, p=0.001) and NAT2*7
      (OR=2.91, 95% CI=1.65-5.12, p=0.0001) alleles. The 7632T/A and 9893C/G
      polymorphisms of CYP2E1 and 1934G/A polymorphism of CYP2D6 did not associate with
      the disease (p>0.05). The haplotypes -1293G:9893C and -1293G:7632T:9893C were
      under-represented (p<0.001), whereas haplotypes -1293C:7632T, -1293C:9893C, 
      1293C:9893G and -1293C:7632T:9893C of the 4 CYP2E1 polymorphisms were over
      represented in patients (p<0.05). CONCLUSION: The CYP2E1 and NAT2 variants
      associated with COPD.

PMID- 17442290
TI  - A novel functional assay for simultaneous determination of total fatty acid beta
      oxidation flux and acylcarnitine profiling in human skin fibroblasts using
      (2)H(31)-palmitate by isotope ratio mass spectrometry and electrospray tandem
      mass spectrometry.
AB  - BACKGROUND: Two separate and complementary assays, total mitochondrial fatty acid
      beta-oxidation (FAO) flux rate and acylcarnitine profiling, have been used to
      establish a definitive diagnosis of FAO defects (FAOD) in cultured cells. We
      developed a novel functional assay for total FAO rate assay by measurement of
      deuterated water enrichment and to combine it with the conventional acylcarnitine
      profiling method into a single tracer incubation experiment. METHODS: Skin
      fibroblasts were incubated in a medium containing universal deuterium-labeled
      palmitate ((2)H(31)-palmitate) and l-carnitine without glucose supplementation
      for 96 h. The culture medium was assayed for deuterated water enrichment using
      isotope ratio mass spectrometry (IRMS) and acylcarnitine profiling by
      electrospray-ionization tandem mass spectrometry (ESI/MS/MS). RESULTS: The
      medians of (2)H(2)O enrichment after 96 h of incubation of (2)H(31)-palmitate of
      the control, other inherited metabolic diseases and FAOD cell lines were 109.9,
      102 and 23.1 ppm/mg protein/96 h, respectively. All fibroblasts with FAOD except
      carnitine uptake defective, multiple acyl-CoA dehydrogenase and short-chain 3
      hydroxyacyl-CoA dehydrogenase deficient cells were well separated from the
      control (<60% control median, p<0.05) and could be identified by IRMS assay.
      Accumulations of disease-specific acylcarnitines due to blockage in the carnitine
      cycle and FAO spiral were also demonstrated by acylcarnitine profiling.
      CONCLUSIONS: This novel functional assay is less time consuming and relatively
      simple by comparison to other published methods and can be used to investigate
      patients suspected to have FAO defects.

PMID- 17442291
TI  - The APRI may be enhanced by the use of the FIBROSpect II in the estimation of
      fibrosis in chronic hepatitis C.
AB  - BACKGROUND: Multiple serum markers to estimate hepatic fibrosis in chronic liver
      disease have been proposed. The AST/Platelet Ratio Index (APRI) is a simple
      biochemical index that has been shown to be useful and accurate in about 50% of
      patients with chronic hepatitis C. We determined if the combination of the APRI
      and the FIBROSpect II, a commercially available hepatic fibrosis marker that
      measures 3 components of the extracellular hepatic matrix, would further help
      distinguish mild from significant fibrosis in a group of patients with chronic
      hepatitis C. METHODS: In an outpatient setting, 93 consecutive patients were
      studied who were undergoing staging liver biopsy for chronic hepatitis C who had
      a liver biopsy length>or=1.5 cm. All had blood drawn at the time of the biopsy.
      Liver biopsies were staged for fibrosis by the Batts Ludwig criteria (F0-F4).
      Patients with previous anti-viral therapy, hepatocellular carcinoma, an organ
      transplant, or co-infection with HIV or hepatitis B were excluded. The APRI was
      calculated and FIBROSpect II determined. RESULTS: The AUC of the ROC curve for
      the APRI and FIBROSpect II were 0.887 and 0.879 respectively. Using cutoffs of
      <or=0.42 for mild fibrosis (F0-F1) and >or=1.2 for significant fibrosis, the APRI
      correctly estimated 19 of 20 patients with mild fibrosis for an NPV of 95.0%, and
      31 of 33 patients with significant fibrosis for a PPV of 93.6%. The FIBROSpect II
      also works best utilizing 2 cutoffs, and using cutoffs of <or=25 and >or=85 it
      correctly identified 18 of 18 patients with mild fibrosis and all 26 patients
      with significant fibrosis for an NPV and PPV of 100% for both. Among the 40
      patients who could not be classified by the APRI, an additional 16 could be
      correctly classified using the FIBROSpect II with cutoffs of <or=25 and >or=85.
      This lowered the indeterminate zone from 43.0 to 25.8%. By combining the APRI and
      the FIBROSpect II, the AUC for the ROC curve improved significantly to 0.931
      (p=0.013). CONCLUSIONS: The APRI and the FIBROSpect II are both accurate tests
      for separating mild from significant fibrosis. By using the APRI as the initial
      screen, >50% of patients with mild or significant fibrosis can be correctly
      identified. If the patient falls in the indeterminate zone, then the more
      expensive FIBROSpect II could be obtained. This strategy could decrease the
      number of liver biopsies.

PMID- 17442293
TI  - Effect of HbS in the determination of HbA2 with the Biorad Variant II analyzer.
AB  - OBJECTIVES: The effect of the presence of HbS in the determination of HbA2 using
      the Biorad Variant II analyzer. DESIGN AND METHODS: The effect of HbS presence in
      the samples was quantified using the HELENA SAS-MX alkaline gel electrophoresis
      kit as the reference method. RESULTS: The %HbA2 values from the Variant II
      analyzer and the HELENA SAS-MX alkaline gel electrophoresis kit show a good
      linear correlation in the absence of HbS. A strong positive bias in the %HbA2
      values from the Variant II is apparent in the presence of HbS in the samples,
      when compared to the alkaline electrophoresis gel. CONCLUSION: The Variant II
      analyzer gives reliable results for %HbA2 determination when no HbS is detectable
      in the samples. When HbS is present, the gel electrophoresis method gives more
      accurate results.

PMID- 17442294
TI  - Vitamin B12 and hepatic enzyme serum levels correlate with interleukin-6 in
      alcohol-dependent individuals without liver disease.
AB  - Alcohol abuse is a major cause of liver cirrhosis as well as chronic liver
      disease. The aim of the present study was to investigate the possible
      correlation, between liver dysfunction biological markers and vitamin B12, with
      interleukin-6, in the serum of alcohol-dependent individuals without liver
      disease (AWLD). In a sample of 43 alcohol abusing/dependent subjects (33 males
      and 10 females) treated on an inpatient basis according to a standard
      detoxification protocol, the serum activities of the hepatic enzymes (ASAT, ALAT,
      gamma-GT), as well as the concentration of B12 and IL-6, were determined on
      admission. A strong positive correlation has been observed between IL-6 and B12,
      ASAT, ALAT, and gamma-GT at the beginning of the detoxification period. The
      results confirmed that in alcohol-dependent individuals, the median serum
      concentration of IL-6, before the beginning of the treatment, had a significant
      positive correlation with the liver dysfunction biological markers and B12. In
      conclusion, IL-6 might be used as an additional diagnostic marker for the degree
      of liver dysfunction in alcohol dependent individuals.

PMID- 17442295
TI  - Association between oxidative stress in pregnancy and preterm premature rupture
      of membranes.
AB  - BACKGROUND: Premature rupture of membranes (PROM) is caused by collagen damage in
      the chorioamniotic sac leading to tearing. Reactive oxygen species (ROS) may be
      the cause of collagen damage. Isoprostanes (F(2)-IP) are produced by ROS attack
      on polyunsaturated fatty acids and are sensitive and specific biomarkers of lipid
      peroxidation in vivo. AIM: To verify whether oxidative stress occurs in
      pregnancies associated with preterm PROM. METHODS: F(2)-IPs were measured in
      amniotic fluid of 16 pregnancies with preterm PROM (Group II) and 97 without PROM
      (Group I). RESULTS: F(2)-IP concentrations (pg/mL) were significantly higher in
      group II than group I (p<0.0001). The ROC curve showed a sensitivity of 100% and
      a specificity of 84.5% at a cut-off of 124.4 pg/mL. CONCLUSIONS: An association
      exists between oxidative stress in pregnancy and preterm PROM. The detection of
      amniotic fluid F(2)-IP concentrations seems to be a reliable predictive index of
      risk of preterm PROM.

PMID- 17442296
TI  - The masked onset priming effect in picture naming.
AB  - Reading aloud is faster when targets (e.g., PAIR) are preceded by visually masked
      primes sharing just the onset (e.g., pole) compared to all different primes
      (e.g., take). This effect is known as the masked onset priming effect (MOPE). One
      crucial feature of this effect is its presumed non-lexical basis. This aspect of
      the MOPE is tested in the current study. Dutch participants named pictures having
      bisyllabic names, which were preceded by visually masked primes. Picture naming
      was facilitated by first-segment but not last-segment primes, and by first
      syllable as well as last-syllable primes. Whole-word primes with first or last
      segment overlap slowed down picture naming latencies significantly. The first
      segment priming effect (i.e., MOPE) cannot be accounted for by non-lexical
      response competition since pictures cannot be named via the non-lexical route.
      Instead, the effects obtained in this study can be accommodated by a speech
      planning account of the MOPE.

PMID- 17442297
TI  - Variability of the twitch parameters of the rat medial gastrocnemius motor units-
      experimental and modeling study.
AB  - In the present study a previously proposed model of a twitch based on an
      analytical function with four-parameters (lead, contraction and half-relaxation
      times and maximum force of the twitch) was validated on 115 motor units (MUs),
      divided into slow (S), fast-fatigue resistant (FR) and fast fatigable (FF) types.
      The original records were collected from electrophysiological experiments
      performed on MUs from the medial gastrocnemius muscle of five rats. Besides the
      easy calculation of the twitch parameters and their variability, the usefulness
      of the model was confirmed by eliminating artifacts and noise in the original
      twitch records, as well as by calculations of the velocity of force increase and
      decrease, the area under force records, and by normalization of all twitches with
      respect to the maximal force and contraction time. It was concluded that: (1) the
      four-parameter twitch model describes precisely the individual contractions of
      various MUs; (2) all physiological twitch parameters are distributed continuously
      and located within overlapping intervals for different MU types; this
      distribution is not linear, but exponential; (3) S MUs can be distinguished from
      fast ones on the basis of some twitch parameters (contraction and half-relaxation
      times, velocity of contraction), but the same cannot be applied for FF and FR
      MUs; (4) the analysis of the normalized twitches reveals the differences in
      shapes for different types of MUs, which shows that twitches of different MUs
      cannot be obtained from one standard pattern scaled in time and force. These
      results may have functional implications for studying effectiveness of twitch
      summation during tetanic contractions and the work performed by various types of
      MUs.

PMID- 17442298
TI  - Cryopreservation of mouse embryoid bodies.
AB  - Cryopreservation of embryonic stem (ES) cells is essential to establish them as a
      resource for regenerative therapy. We evaluated survival adhesion rate, cell
      structure, gene expression, and multipotency of frozen and thawed embryoid bodies
      (EBs) derived from mouse ES cells. EBs were cryopreserved using the BICELL and
      the Program Freezer. After one week the EBs were thawed and cultured. EBs
      prepared in the Program Freezer had the highest survival adhesion (Program
      Freezer; 55-69%, BICELL; 30-38%). Though many cells in the thawed EBs were
      damaged, some were not, especially those prepared in the Program Freezer. RT-PCR
      analysis showed that genes characteristic of the three embryonic germ layers were
      expressed in thawed EBs cultured for one week. EBs transplanted into mice formed
      teratomas consisting of cells derived from the three germ layers. In conclusion,
      EBs frozen in the Program Freezer had higher survival adhesion rates compared to
      the BICELL and formed differentiated cells characteristic of the three embryonic
      germ layers.

PMID- 17442299
TI  - Wnt/beta-catenin signaling has an essential role in the initiation of limb
      regeneration.
AB  - Anuran (frog) tadpoles and urodeles (newts and salamanders) are the only
      vertebrates capable of fully regenerating amputated limbs. During the early
      stages of regeneration these amphibians form a "blastema", a group of mesenchymal
      progenitor cells that specifically directs the regrowth of the limb. We report
      that wnt-3a is expressed in the apical epithelium of regenerating Xenopus laevis
      limb buds, at the appropriate time and place to play a role during blastema
      formation. To test whether Wnt/beta-catenin signaling is required for limb
      regeneration, we created transgenic X. laevis tadpoles that express Dickkopf-1
      (Dkk1), a specific inhibitor of Wnt/beta-catenin signaling, under the control of
      a heat-shock promoter. Heat-shock immediately before limb amputation or during
      early blastema formation blocked limb regeneration but did not affect the
      development of contralateral, un-amputated limb buds. When the transgenic
      tadpoles were heat-shocked following the formation of a blastema, however, they
      retained the ability to regenerate partial hindlimb structures. Furthermore, heat
      shock induced Dkk1 blocked fgf-8 but not fgf-10 expression in the blastema. We
      conclude that Wnt/beta-catenin signaling has an essential role during the early
      stages of limb regeneration, but is not absolutely required after blastema
      formation.

PMID- 17442301
TI  - XSip1 neuralizing activity involves the co-repressor CtBP and occurs through BMP
      dependent and independent mechanisms.
AB  - The DNA-binding transcription factor Smad-interacting protein-1 (Sip1) (also
      named Zfhx1b/ZEB2) plays essential roles in vertebrate embryogenesis. In Xenopus,
      XSip1 is essential at the gastrula stage for neural tissue formation, but the
      precise molecular mechanisms that underlie this process have not been fully
      identified yet. Here we show that XSip1 functions as a transcriptional repressor
      during neural induction. We observed that constitutive activation of BMP
      signaling prevents neural induction by XSip1 but not the inhibition of several
      epidermal genes. We provide evidence that XSip1 binds directly to the BMP4
      proximal promoter and modulates its activity. Finally, by deletion and mutational
      analysis, we show that XSip1 possesses multiple repression domains and that CtBPs
      contribute to its repression activity. Consistent with this, interference with
      XCtBP function reduced XSip1 neuralizing activity. These results suggest that
      Sip1 acts in neural tissue formation through direct repression of BMP4 but that
      BMP-independent mechanisms are involved as well. Our data also provide the first
      demonstration of the importance of CtBP binding in Sip1 transcriptional activity
      in vivo.

PMID- 17442302
TI  - Baicalein impairs vascular tone in normal rat aortas: role of superoxide anions.
AB  - Acute exposure to the flavonoid baicalein inhibited endothelium-dependent
      relaxation in physiological arteries, although the mechanisms are not fully
      understood. We investigated the effect of baicalein on vascular tone in Wistar
      Kyoto (WKY) rat isolated aortic rings in the presence and absence of oxidative
      stress to further determine the underlying mechanisms. Exposure to baicalein (10
      microM) completely abolished endothelium-dependent relaxation induced by
      acetylcholine and attenuated significantly the endothelium-independent relaxation
      induced by sodium nitroprusside. Baicalein, similar to Nomega-nitro-L-arginine
      methyl ester (L-NAME, 10 microM), potentiated significantly the contractile
      response of aortic rings to alpha1-adrenoceptor agonist phenylephrine. In the
      presence of L-NAME the baicalein effect on phenylphrine contraction or
      acetylcholine relaxation was unaltered, suggesting that these effects of
      baicalein are (like L-NAME effect) endothelial nitric oxide synthase
      (eNOS)/endothelium-derived nitric oxide-dependent. Inhibition of cyclooxygenase
      activity with indomethacin (10 microM) or scavenging of superoxide anions with
      superoxide dismutase (150 units/ml), but not scavenging of hydrogen peroxide with
      catalase (800 units/ml), enhanced significantly by an essentially similar extent
      the relaxation to acetylcholine in baicalein-pretreated aortic rings. Relaxant
      effect to acetylcholine was significantly attenuated in control aortic rings, but
      was completely abolished in baicalein-pretreated aortic rings in the presence of
      reduced form of beta-nicotinamide adenine di-nucleotide (beta-NADH, 300 microM).
      Baicalein blocked beta-NADH (300 microM)-induced transient contractions,
      suggesting that baicalein may have inhibited activity of NADH/NADPH-oxidase.
      Baicalein did not alter the failure of acetylcholine to induce relaxation in the
      presence of pyrogallol (300 microM). In summary, acute exposure to baicalein
      impairs eNOS/endothelium-derived nitric oxide-mediated vascular tone in rat
      aortas through the inhibition of endothelium-derived nitric oxide bioavailability
      coupled to reduced bioactivity of endothelium-derived nitric oxide and to
      cyclooxygenase-mediated release of superoxide anions.

PMID- 17442300
TI  - The Hectd1 ubiquitin ligase is required for development of the head mesenchyme
      and neural tube closure.
AB  - Closure of the cranial neural tube depends on normal development of the head
      mesenchyme. Homozygous-mutant embryos for the ENU-induced open mind (opm)
      mutation exhibit exencephaly associated with defects in head mesenchyme
      development and dorsal-lateral hinge point formation. The head mesenchyme in opm
      mutant embryos is denser than in wildtype embryos and displays an abnormal
      cellular organization. Since cells that originate from both the cephalic paraxial
      mesoderm and the neural crest populate the head mesenchyme, we explored the
      origin of the abnormal head mesenchyme. opm mutant embryos show apparently normal
      development of neural crest-derived structures. Furthermore, the abnormal head
      mesenchyme in opm mutant embryos is not derived from the neural crest, but
      instead expresses molecular markers of cephalic mesoderm. We also report the
      identification of the opm mutation in the ubiquitously expressed Hectd1 E3
      ubiquitin ligase. Two different Hectd1 alleles cause incompletely penetrant
      neural tube defects in heterozygous animals, indicating that Hectd1 function is
      required at a critical threshold for neural tube closure. This low penetrance of
      neural tube defects in embryos heterozygous for Hectd1 mutations suggests that
      Hectd1 should be considered as candidate susceptibility gene in human neural tube
      defects.

PMID- 17442303
TI  - Highly active antiretroviral therapy of cognitive dysfunction and neuronal
      abnormalities in SCID mice with HIV encephalitis.
AB  - Our objective was to determine if highly active antiretroviral therapy (HAART),
      previously shown to ameliorate several pathological features of HIV encephalitis
      (HIVE) in a SCID mouse model, would also reduce additional established
      pathological features of HIV: cognitive dysfunction, TNF-alpha, production, and
      reduced MAP-2 expression. SCID mice with HIVE and control mice inoculated with
      uninfected monocytes were administered HAART or saline. The HIV pathological
      features evaluated included astrogliosis, viral load, neuronal apoptosis, MAP-2
      expression, mouse TNF-alpha mRNA production and learning acquisition and
      retention. HAART reduced the HIV-induced viral load, and the astro- and
      microgliosis as previously observed; this effect was extended to HIV-induced
      increases in TNF-alpha mRNA production. In contrast, although HIV produced the
      cognitive deficits previously observed and also decreased MAP-2 expression in the
      area surrounding the injected HIV-infected human monocytes, HAART did not
      attenuate these effects. Interestingly, there was no neuronal apoptosis evident
      at the time point reflecting the above pathology. The results of this study
      combined with previous reports indicate that HAART reduces TNF-alpha mRNA, viral
      load and astrogliosis; however, HAART does not improve HIV-induced cognitive
      dysfunction or MAP-2 decreases. These results suggest that viral load,
      astrogliosis, TNF- alpha and apoptosis are not prominent in the pathogenesis of
      early functional deficits related to decreased MAP-2 expression or cognitive
      dysfunction in HIVE in SCID mice.

PMID- 17442304
TI  - Cyclicity of spontaneous recurrent seizures in pilocarpine model of temporal lobe
      epilepsy in rat.
AB  - Pilocarpine administration to rats results in status epilepticus (SE) and after a
      latency period to the occurrence of spontaneous seizures. The model is commonly
      used to investigate mechanisms of epileptogenesis as well as the antiepileptic
      effects of novel compounds. Surprisingly, there have been no video-EEG studies
      determining the duration of latency period from SE to the appearance of the first
      spontaneous seizures or the type and frequency of spontaneous seizures at early
      phase of pilocarpine-induced epilepsy even though such information is critical
      for design of such studies. To address these questions, we induced SE with
      pilocarpine in 29 adult male Wistar rats with cortical electrodes. Rats were
      continuously video-EEG monitored during SE and up to 23 days thereafter. The
      first spontaneous seizures occurred 7.2+/-3.6 days after SE. During the follow
      up, the mean daily seizure frequency was 2.6+/-1.9, the mean seizure duration
      47+/-7 s, and the mean behavioral seizure score 3.2+/-0.9. Typically first
      seizures were partial (score 1-2). Interestingly, spontaneous seizures occurred
      in clusters with cyclicity, peaking every 5 to 8 days. These data show that in
      the pilocarpine model of temporal lobe epilepsy the latency period is short.
      Because many of the early seizures are partial and the seizures occur in
      clusters, the true phenotype of epilepsy triggered by pilocarpine-induced SE may
      be difficult to characterize without continuous long-term video-EEG monitoring.
      Finally, our data suggest that the model can be used for studies aiming at
      identifying the mechanisms of seizure clustering.

PMID- 17442305
TI  - Plasmodium falciparum: VAR2CSA expressed during pregnancy-associated malaria is
      partially resistant to proteolytic cleavage by trypsin.
AB  - In areas of high Plasmodium falciparum transmission, immunity to malaria is
      acquired during childhood, so that adults in general are clinically immune. One
      exception is that first-time pregnant women are susceptible to pregnancy
      associated malaria caused by accumulation of parasites in the placenta. Pregnancy
      associated variant surface antigens (VSAPAM) mediate binding of the infected
      erythrocyte to chondroitin sulphate proteoglycans in the placental intervillous
      space. Several lines of evidence indicate that the molecular identity of VSAPAM
      is VAR2CSA, a relatively conserved member of the P. falciparum erythrocyte
      membrane protein 1 (PfEMP1) family. While native PfEMP1 molecules expressed on
      the infected erythrocyte surface generally are sensitive to mild trypsinization,
      some VSAPAM expressing parasite lines are resistant. This finding has led to the
      suggestion that molecules other than PfEMP1, or at least several different PfEMP1
      families mediate the VSAPAM phenotype. To address this issue we incubated three
      different VAR2CSA expressing parasite lines with trypsin and found that
      polymorphic VAR2CSA variants can be both protease resistant and sensitive.
      Trypsin treatment resulted in loss of ability to adhere to CSA and loss of sex
      specific antibody recognition of the surface of the infected erythrocyte in one
      sensitive isolate, whereas CSA binding and sex-specific recognition were largely
      unaffected by trypsin treatment in two resistant isolates. These results support
      the hypothesis that VAR2CSA mediates the adhesive and antigenic phenotypes shown
      by parasites causing placental malaria.

PMID- 17442306
TI  - Plasmodium berghei XAT: protective 155/160 kDa antigens are located in
      parasitophorous vacuoles of schizont-stage parasite.
AB  - Effective blood-stage malaria vaccine candidates have been mainly developed from
      the proteins in exposed locations on the parasite such as the surface of free
      merozoites or infected red blood cells. In the present study, we identified and
      localized novel protective antigens derived from the blood-stage of Plasmodium
      berghei XAT after establishment of hybridomas producing protective monoclonal
      antibodies (mAbs) against the parasites. The protective antigens were expressed
      in schizonts but not in trophozoites, and located in the parasitophorous vacuoles
      in the infected erythrocyte cytoplasm. The antigens, with molecular weight of
      155/160 kDa, were not identical to any merozoite/schizont antigens that have been
      reported as target molecules recognized by mAbs developed to rodent malaria
      parasites. The characterization of new malarial antigenic targets of potentially
      protective antibody responses following infection would give us new insights for
      the selection of candidate antigens for malaria vaccine.

PMID- 17442308
TI  - Entamoeba invadens: the requirement for galactose ligands during encystment.
AB  - During periods of stress, trophozoites of Entamoeba invadens (strain IP-1)
      undergo a process of differentiation (encystment) that results in a dormant cyst
      with a chitin-containing cyst wall. Encystment can be induced by resuspension of
      trophozoites from growth medium into a diluted glucose-free medium (47% LG)
      containing 5% adult bovine serum (ABS). ABS is thought to be a source of gal
      terminated ligands that are required for high levels of encystment. After
      resuspension of trophozoites in 47% LG, encystment cultures were examined every
      2h for responses to the (i) addition of 10mM free-galactose, (ii) resuspension of
      cells to serum-free medium, (iii) and dilution of encysting cultures to cell
      densities below that known to support full encystment (from 5 x 10(5) to 1 x
      10(4)cells/ml). The role of serum components (and the gal-terminated ligand
      asialofetuin; ASF) adsorbed onto the surface upon which encystment proceeds, and
      their effect on the multi-cellular aggregation patterns formed during encystment,
      were also investigated. The addition of free-galactose reduced the levels of
      encystment (compared with the control) even when added at 10h after resuspension
      of trophozoites in 47% LG. The requirement for the presence of ABS during
      encystment was lost within 6h, with levels of encystment of cells washed free of
      serum reaching 80% of the control. The ability of cells to encyst when diluted to
      a cell density below that normally thought to support encystment reached over 50%
      by 8h. Efficient encystment could be obtained in 47% LG in the absence of ABS or
      ASF using pre-treated glass culture tubes. Encystment (47% LG; 5% ABS) using
      ultra low attachment plates was poor, suggesting attachment of cells to a surface
      via gal-terminated ligands was important for efficient encystment. The results
      suggest that ABS is probably not the only source of gal-terminated ligands
      necessary for high levels of encystment in 47% LG. While serum may provide a
      source of ligands which enhance the levels of encystment initially, other gal
      terminated ligands possibly released by the encysting cells are still required
      for the completion of the encystment process and the formation of mature cysts.
      In addition, the gal-terminated ligands necessary for encystment efficiency may
      be adsorbed onto the glass surface of culture tubes and aid the initial
      aggregation process, as well as be involved in cell signaling during the
      encystment process.

PMID- 17442309
TI  - Babesia bovis: the development of an expression oligonucleotide microarray.
AB  - The availability of a stage-specific Babesia bovis expression profile can
      facilitate the identification of candidate vaccine antigens. In addition, highly
      expressed genes during a particular developmental stage may suggest their
      relevance during that stage. In this study, we generated and validated a custom
      B. bovis high density oligonucleotide microarray that can be used to examine gene
      expression levels. An expression profile of in vitro cultured intraerythrocytic
      stage genes that could be distinguished from contaminating host message was
      established, and the expression levels of over 1000 genes were ranked. Ranking
      order was validated using quantitative real time PCR on a twelve randomly
      selected open reading frames whose expression levels range from the highest to
      the acceptable lowest. Expression of annotated ORFs was consistent with results
      from a recently published B. bovis expression sequence tag study. Therefore, we
      conclude that the microarray is suitable for analyzing B. bovis gene expression,
      and present the complete B. bovis infected erythrocyte expression profile.

PMID- 17442307
TI  - Brugia malayi: comparison of protective immune responses induced by Bm-alt-2 DNA,
      recombinant Bm-ALT-2 protein and prime-boost vaccine regimens in a jird model.
AB  - Immunization of jirds with Bm-alt-2 elicited partial protection against challenge
      infection with the filarial parasite Brugia malayi. In this study, we initially
      compared the protective immune responses elicited following immunization with
      recombinant Bm-ALT-2 protein regimen and Bm-alt-2 DNA regimen. These studies
      showed that protein vaccination conferred approximately 75% protection compared
      to DNA vaccination that conferred only 57% protection. Analysis of the protective
      immune responses showed that the protein immunization promoted a Th2-biased
      response with an increase in IL-4, IL-5 and IgG1 responses, whereas, the DNA
      vaccine promoted a Th1-biased response with profound IFN-gamma and IgG2a
      responses. Since protein vaccination gave better results than DNA vaccination, we
      then wanted to evaluate whether a prime-boost vaccination that combined DNA prime
      and protein boost will significantly increase the protective responses induced by
      the protein vaccine. Our results suggest that prime-boost vaccination had no
      added advantage and was comparatively less effective (64% protection) than the Bm
      ALT-2 protein alone vaccination. Prime boost vaccination generated mixed Th1/Th2
      responses with a slightly diminished Th2 responses compared to protein
      vaccination. Thus, our results suggest that Bm-ALT-2 protein vaccination regimen
      may be slightly better than prime-boost vaccine regimen and the mechanism of
      protection appears to be largely mediated by a Th2-biased response.

PMID- 17442310
TI  - Expression and functional role of formyl peptide receptor in human bone marrow
      derived mesenchymal stem cells.
AB  - We investigated the expression of formyl peptide receptor (FPR) and its
      functional role in human bone marrow-derived mesenchymal stem cells (MSCs). We
      analyzed the expression of FPR by using ligand-binding assay with radio-labeled N
      formyl-met-leu-phe (fMLF), and found that MSCs express FPR. FMLF stimulated
      intracellular calcium increase, mitogen-activated protein kinases activation, and
      Akt activation, which were mediated by G(i) proteins. MSCs were chemotactically
      migrated to fMLF. FMLF-induced MSC chemotaxis was also completely inhibited by
      pertussis toxin, LY294002, and PD98059, indicating the role of G(i) proteins,
      phosphoinositide 3-kinase, and extracellular signal regulated protein kinase. N
      terminal fragment of annexin-1, Anx-1(2-26), an endogenous agonist for FPR, also
      induced chemotactic migration of MSCs. Thus MSCs express functional FPR,
      suggesting a new (patho)physiological role of FPR and its ligands in regulating
      MSC trafficking during induction of injured tissue repair.

PMID- 17442311
TI  - Activation of the unfolded protein response and alternative splicing of ATF6alpha
      in HLA-B27 positive lymphocytes.
AB  - Misfolding of major histocompatibility complex (MHC) class I molecules has been
      implicated in the rheumatic autoimmune disease ankylosing spondylitis (AS), and
      has been linked to the unfolded protein response (UPR) in rodent AS models. XBP1
      and ATF6alpha are two important transcription factors that initiate and co
      ordinate the UPR. Here we show that misoxidised MHC class I heavy chains activate
      XBP1 processing in a similar manner to tunicamycin, with tunicamycin and
      dithiothreitol (DTT) inducing differential XBP1 processing. Unexpectedly,
      ATF6alpha mRNA is alternatively spliced during reducing stress in lymphocytes.
      This shorter ATF6alpha message lacks exon 7 and may have a regulatory role in the
      UPR.

PMID- 17442312
TI  - Workshop report: evaluation of genetic and epigenetic risks associated with
      assisted reproductive technologies and infertility.
AB  - In January 2005, the Assisted Reproductive Technologies (ART) Workshop:
      Evaluation of Genetic and Epigenetic Risks Associated with Assisted Reproductive
      Technologies and Infertility was convened to evaluate current data on genetic and
      epigenetic risks to offspring conceived after a period of infertility and/or via
      ARTs. Formal presentations and workshop breakout groups reviewed the information
      from a broad range of disciplines and discussed issues regarding study design,
      molecular approaches, animal model systems, clinical outcomes, and ethical,
      legal, and psychosocial issues. The key recommendations of the workshop are that:
      [1] ART research and education should flow from clinical and basic science
      studies of the fundamental biology of early mammalian embryonic development, with
      a focus on how infertility and/or ART might disrupt such processes; [2] such
      research should include the emerging area of epigenetics and its potential role
      in reproductive health outcomes; [3] methods for the standardization of data
      collection and for handling and analysis should be employed, including precise
      definitions of obstetric and perinatal terminology; [4] much greater awareness
      and ongoing evaluation of the psychosocial impact of ART and ART research on
      women, their partners, and their offspring are required; and [5] effective
      methods of knowledge transfer need to be developed and delivered to healthcare
      providers and to the general public regarding reproductive planning, infertility,
      and ART, including the potential risks associated with each.

PMID- 17442313
TI  - Laparoscopic electrodessication of an interstitial pregnancy.
AB  - OBJECTIVE: To report on the case of a woman who presented with lower abdominal
      pain and vaginal bleeding, and who was diagnosed with early interstitial
      pregnancy. DESIGN: Case report. SETTING: Medical center and teaching hospital.
      PATIENT: A 32-year-old woman with a previous history of ectopic pregnancy.
      INTERVENTION(S): Imaging study with ultrasonography and laparoscopy. MAIN OUTCOME
      MEASURE(S): Complete resolution of the ectopic pregnancy at the interstitial site
      of the amputated fallopian tube, and resumption of menstruation. RESULT(S): Other
      causes of internal bleeding were ruled out. Menstruation resumed 30 days after
      the procedure. CONCLUSION: An early interstitial pregnancy may be successfully
      managed with laparoscopic electrodessication.

PMID- 17442314
TI  - Birth after intracytoplasmic sperm injection with use of testicular sperm from
      men with Kartagener or immotile cilia syndrome.
AB  - OBJECTIVE: To describe a case of intracytoplasmic sperm injection (ICSI) with
      testicular sperm in men with immotile cilia syndrome and to discuss the role of
      micromanipulation in the treatment of these patients. DESIGN: Case report.
      SETTING: Private infertility clinic and assisted reproduction unit. PATIENT(S):
      Couple with male factor infertility due to Kartagener's/immotile cilia syndrome.
      INTERVENTION(S): The patient's partner underwent ICSI with testicular sperm. MAIN
      OUTCOME MEASURE(S): Semen characteristics, sperm viability, fertilization and
      cleavage rate, pregnancy, and birth after ICSI. RESULT(S): With testicular sperm,
      the two pronuclear fertilization rates were 53%. ICSI was successful in the first
      cycle. The uncomplicated pregnancy resulted in the birth of two healthy children,
      male/female twins. CONCLUSION(S): With testicular sperm, successful oocyte
      fertilization after ICSI in couples with male Kartagener or immotile cilia
      syndrome is possible with nonprogressive motile sperm resulting in clinically
      healthy offsprings.

PMID- 17442315
TI  - Association of the GAA1013-->GAG polymorphism of the insulin-like growth factor-1
      receptor (IGF1R) gene with premature pubarche.
AB  - OBJECTIVE: A single-nucleotide polymorphism (SNP), the G variant in codon 1013
      (GAA1013-->GAG) of the insulin-like growth factor-1 (IGF-1) receptor (IGFIR)
      gene, has been associated with higher IGF-1 concentrations in Caucasian subjects.
      Because elevated serum levels of IGF-1 have been described in children with
      premature pubarche (PP) and in adolescent girls with hyperandrogenism, we tested
      the a priori hypothesis that the frequency of the A-->G variant would be
      overrepresented among children with PP. DESIGN: Case-control association study.
      SETTING: University-based pediatric endocrinology practice. PATIENT(S): Sixty
      nine children (63 girls and 6 boys) with PP, 52 adolescent girls with
      hyperandrogenism, and 92 healthy subjects. INTERVENTION(S): Blood was obtained
      for genotype analysis, glucose measurement, and hormone (A, insulin, 17
      hydroxyprogesterone, and T) determinations. MAIN OUTCOME MEASURE(S): Frequency of
      the SNP in the IGF1R gene and correlation of this SNP with hormone
      concentrations. RESULT(S): Distribution of the G allele was statistically
      significantly different between the children with PP and the healthy control
      subjects, independent of insulin sensitivity. CONCLUSION(S): This common SNP in
      the IGF1R gene may be associated with PP caused by premature adrenarche in
      children. Because PP has been associated with higher IGF-1 concentrations, these
      data suggest a potential molecular basis for prior clinical observations of
      elevated IGF-1 concentrations in children with PP.

PMID- 17442317
TI  - A stable multimodel scheme control for the regulation of the transient behavior
      of a tunnel-diode trigger circuit.
AB  - A multimodel scheme is designed for a triggering tunnel-diode circuit. The scheme
      improves the transient behavior during the transition time period after switching
      from a stable system equilibrium point to another one which is known as a
      triggering process. Each model is obtained by a linearization of the circuit near
      an equilibrium point. Moreover, each of these models can be described as a
      combination of two other transfer functions describing the linearized plant
      behavior near two different equilibrium points. The scheme chooses online the
      model with the best tracking performance in order to generate the control law.
      Different reference transfer functions are proposed with the aim of generating
      the desired transient in the triggering process. Some simulations show the
      usefulness of this scheme.

PMID- 17442316
TI  - Transient genital abnormalities in striped hyenas (Hyaena hyaena).
AB  - The highly masculinized genitalia of female spotted hyenas Crocuta crocuta is
      unique among mammals: Crocuta have no external vagina so urination, penile
      intromission and parturition take place through the clitoris, which mimics a
      fully erectile male penis. Among hyenids, virilization of external female
      genitalia has previously been observed only in Crocuta, so functional
      explanations of masculinization have focused on aspects of social ecology unique
      to the species. Here we first show that the striped hyena Hyaena hyaena exhibits
      both unusual similarity in male and female androgen concentrations and transient
      genital anomalies characterized by a convergence in genital appearance among
      young males and females. We then evaluate hypotheses regarding the evolution of
      genital masculinization in the Hyaenidae and other taxa. Hyaena are behaviorally
      solitary, so discovery of unusual genital development patterns in this species
      does not support any current evolutionary models for masculinization in Crocuta,
      which all rely on the trait originating within a highly social species. Some
      hypotheses can be modified so that masculinization in Crocuta represents an
      extreme elaboration of a preexisting trait, shared as a homology with Hyaena.

PMID- 17442318
TI  - Contrasting genetic structure in Plasmodium vivax populations from Asia and South
      America.
AB  - Populations of Plasmodium falciparum show striking differences in linkage
      disequilibrium, population differentiation and diversity, but only fragmentary
      data exists on the genetic structure of Plasmodium vivax. We genotyped nine
      tandem repeat loci bearing 2-8 bp motifs from 345 P. vivax infections collected
      from three Asian countries and from five locations in Colombia. We observed 9-37
      alleles per locus and high diversity (He=0.72-0.79, mean=0.75) in all countries.
      Numbers of multiple clone infections varied considerably: these were rare in
      Colombia and India, but > 60% of isolates carried multiple alleles in at least
      one locus in Thailand and Laos. However, only one or two of the nine loci show >1
      allele in many samples, suggesting that mutation within infections may result in
      overestimation of true multiple carriage rates. Identical nine-locus genotypes
      were frequently found in Colombian populations, contributing to strong linkage
      disequilibrium. These identical genotypes were strongly clustered in time,
      consistent with epidemic transmission of clones and subsequent breakdown of
      allelic associations, suggesting high rates of inbreeding and low effective
      recombination rates in this country. In contrast, identical genotypes were rare
      and loci were randomly associated in all three Asian populations, consistent with
      higher rates of outcrossing and recombination. We observed low but significant
      differentiation between different Asian countries (standardized FST = 0.13-0.45).
      In comparison, we see greater differentiation between collection locations within
      Colombia (standardized FST = 0.4-0.7), and strong differentiation between
      continents (standardized FST = 0.48-0.79). The observed heterogeneity in multiple
      clone carriage rates, linkage disequilibrium and population differentiation are
      similar in some, but not all, respects to those observed in P. falciparum, and
      have important implications for the design of association mapping studies, and
      interpretation of P. vivax epidemiology.

PMID- 17442319
TI  - Aneurysmal wall calcification predicts natural history of small abdominal aortic
      aneurysms.
AB  - BACKGROUND: The biomechanical properties of the abdominal aortic aneurysm (AAA)
      wall may hold predictive potential. This study aims to study the potential role
      of wall calcification in small AAAs. METHODS: Initial AAA calcification was
      determined by ultrasonography to be either more or less than 50% of the initial
      maximal AAA circumference in 122 men with an initial AAA sized 30-49 mm in
      maximal diameter. The patients were offered annual control scans and refered for
      surgery, if the AAA diameter exceeded 50 mm. Surgery for AAA from the date of
      inclusion to 15 March 2005 was identified in the national vascular registry
      "Karbase". Mean follow time was 6.15 years. RESULTS: The mean annual growth rate
      was significantly lower in men with an AAA wall calcification above than below
      50% (1.72 mm versus 2.97 mm, P=0.001). The finding persisted after multivariate
      linear regression analysis adjusting for age, smoking and aspirin use. A total of
      12 men with AAA calcification above 50% were operated compared with 25 men with
      an AAA calcification below 50% (risk ratio: 0.35 (0.18-0.71), P=0.003). The
      difference in risk persisted after adjustment for age, smoking and use of aspirin
      (risk ratio: 0.36 (0.18-0.74), P=0.008). CONCLUSION: The calcification content in
      small AAA predicts the natural history of small AAA.

PMID- 17442320
TI  - Feasibility of noninvasive evaluation of biophysical properties of tissue
      engineered cartilage by using quantitative MRI.
AB  - The application of tissue-engineered cartilage in a clinical setting requires a
      noninvasive method to assess the biophysical and biochemical properties of the
      engineered cartilage. Since articular cartilage is composed of 70-80% water and
      has dense extracellular matrixes (ECM), it is considered that the condition of
      the water molecules in the tissue is correlated with its biomechanical property.
      Therefore, magnetic resonance imaging (MRI) represents a potential approach to
      assess the biophysical property of the engineered cartilage. In this study, we
      test the hypothesis that quantitative MRI can be used as a noninvasive assessment
      method to assess the biophysical property of the engineered cartilage. To
      reconstruct a model of cartilaginous tissue, chondrocytes harvested from the
      humeral head of calves were embedded in an agarose gel and cultured in vitro up
      to 4 weeks. Equilibrium Young's moduli were determined from the stress relaxation
      tests. After mechanical testing, MRI-derived parameters (longitudinal relaxation
      time T1, transverse relaxation time T2, and water self-diffusion coefficient D)
      were measured. The equilibrium Young's modulus of the engineered cartilage showed
      a tendency to increase with an increase in the culture time, whereas T1 and D
      decreased. Based on a regression analysis, T1 and D showed a strong correlation
      with the equilibrium Young's modulus. The results showed that T1 and D values
      derived from the MRI measurements could be used to noninvasively monitor the
      biophysical properties of the engineered cartilage.

PMID- 17442321
TI  - Adaptive usage of the Butterworth digital filter.
AB  - The Butterworth lowpass filter is a conventional tool that has been commonly used
      in gait analysis applications. Its operation mainly depends on the selection of
      the cut-off frequency, which must be done based on the condition of the raw
      signal assuming that it is stationary. This tool is unable to deal with
      nonstationary signals especially if impact is involved. In this paper, a modified
      version of the Butterworth filter that can handle nonstationary signals is
      presented. The new filter has a variable cut-off frequency distribution defined
      for each data point, which is determined by local signal characteristics. Because
      of its adaptive nature, it is possible for the filter to accommodate changes in
      the frequency content of the signal.

PMID- 17442322
TI  - Comparison of the sensitivities of seven N-nitrosamines in pre-screened waters
      using an automated preconcentration system and gas chromatography with different
      detectors.
AB  - A simple, expeditious procedure for confirming the presence of N-nitrosamines in
      previously screened positive water samples was proposed. Water samples were
      continuously aspirated into a photometric flow system for screening. Positive
      samples were then confirmed and N-nitrosamines were identified by gas
      chromatography using different detectors (mass spectrometry, flame ionization and
      nitrogen-phosphorus). The system for the screening purpose was based on the
      preconcentration of the analytes onto a sorbent column, elution, and
      derivatization to form nitrite, then formation of a coloured product (Griess
      reaction) and photometric detection. The detection limits of the gas
      chromatographic method for 100 ml of sample were 2.0-3.5 microg/l, 20-80 and 3-13
      ng/l for flame ionization, nitrogen-phosphorus and mass spectrometric detectors,
      respectively. The precision as RSD was similar for all detectors (3.0-6.5%). The
      screening of different types of water showed that wastewaters contain levels of N
      nitrosamines that can be detected only using MS as a detector.

PMID- 17442323
TI  - Pressurized capillary electrochromatographic analysis of water-soluble vitamins
      by combining with on-line concentration technique.
AB  - A pressurized capillary electrochromatography (pCEC) system was developed for the
      separation of water-soluble vitamins, in which UV absorbance was used as the
      detection method and a monolithic silica-ODS column as the separation column. The
      parameters (type and content of organic solvent in the mobile phase, type and
      concentration of electrolyte, pH of the electrolyte buffer, applied voltage and
      flow rate) affecting the separation resolution were evaluated. The combination of
      two on-line concentration techniques, namely, solvent gradient zone sharpening
      effect and field-enhanced sample stacking, was utilized to improve detection
      sensitivity, which proved to be beneficial to enhance the detection sensitivity
      by enabling the injection of large volumes of samples. Coupling electrokinetic
      injection with the on-line concentration techniques was much more beneficial for
      the concentration of positively charged vitamins. Comparing with the conventional
      injection mode, the enhancement in the detection sensitivities of water-soluble
      vitamins using the on-line concentration technique is in the range of 3 to 35
      fold. The developed pCEC method was applied to evaluate water-soluble vitamins in
      corns.

PMID- 17442324
TI  - Comprehensive multi-residue method for the target analysis of pesticides in crops
      using liquid chromatography-tandem mass spectrometry.
AB  - A liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS) multi
      residue method for the simultaneous target analysis of a wide range of pesticides
      and metabolites in fruit, vegetables and cereals has been developed. Gradient
      elution has been used in conjunction with positive mode electrospray ionization
      tandem mass spectrometry to detect up to 171 pesticides and/or metabolites in
      different crop matrices using a single chromatographic run. Pesticide residues
      were extracted/partitioned from the samples with acetone/dichloromethane/light
      petroleum. The analytical performance was demonstrated by the analysis of
      extracts from lettuce, orange, apple, cabbage, grape and wheat flour, spiked at
      three concentration levels ranging from 0.01 to 0.10 mg/kg for each pesticide
      and/or metabolite. In general, recoveries ranging from 70 to 110%, with relative
      standard deviations better than 15%, were obtained. The recovery and
      repeatability data are in good accordance with EU guidelines for pesticide
      residue analysis. The limit of quantification for all targeted pesticides and
      metabolites tested was 0.01 mg/kg. The selectivity and robustness of the LC-MS/MS
      method was demonstrated by a 1-year comparison of its analytical results with
      those obtained from our validated GC and LC multi-residue methods applied to more
      than 3500 routine samples. The validated LC-MS/MS method has been implemented in
      our analytical scheme since 2004, replacing four of the conventional detection
      methods, i.e. GC-flame-photometric detection (acephate, methamidophos, etc.), GC
      nitrogen-phosphorus detection, LC-UV detection (carbendazim, thiabendazole,
      imazalil and prochloraz) and LC-fluorescence detection (N-methylcarbamate
      pesticides). During a 3-year period, the LC-MS/MS method has been applied to the
      analyses of more than 12,000 samples.

PMID- 17442325
TI  - Surface Lewis acid-base properties of polymers measured by inverse gas
      chromatography.
AB  - Surface Lewis acid-base properties are significant for polymers materials. The
      acid constant, K(a) and base constant, K(b) of many polymers were characterized
      by some researchers with inverse gas chromatography (IGC) in recent years. In
      this paper, the surface acid-base constants, K(a) and K(b) of 20 kinds of
      polymers measured by IGC in recent years are summarized and discussed, including
      seven polymers characterized in this work. After plotting K(b) versus K(a), it is
      found that the polymers can be encircled by a triangle. They scatter in two
      regions of the triangle. Four polymers exist in region I. K(b)/K(a) of the
      polymers in region I are 1.4-2.1. The other polymers exist in region II. Most of
      the polymers are relative basic materials.

PMID- 17442326
TI  - Characterization of high molecular weight polyethylenes using high temperature
      asymmetrical flow field-flow fractionation with on-line infrared, light
      scattering, and viscometry detection.
AB  - High temperature asymmetrical flow field-flow fractionation (HTAF4) coupled to
      infrared (IR), multi-angle light scattering (MALS), and viscometry (Visc)
      detection is introduced as a tool for the characterization of high molecular
      weight polyethylenes. The high molecular weight fraction strongly affects the
      rheological behaviour and processability of polyethylene materials and can often
      not be accurately resolved by current technology such as high temperature size
      exclusion chromatography (HTSEC). Molecular weight (M), radius of gyration (Rg),
      and intrinsic viscosity [eta] of linear high density polyethylene (HDPE) and
      branched low density polyethylene (LDPE) samples are studied in detail by HTAF4
      and are compared to HTSEC. HTAF4 showed a better separation and mass recovery
      than HTSEC for very high molecular weight fractions in HDPE and LDPE samples. As
      no stationary phase is present in an HTAF4 channel, the technique does not show
      the typical drawbacks associated with HTSEC analysis of high molecular weight
      polyethylenes, such as, exclusion effects, shear degradation, and anomalous late
      elution of highly branched material. HTAF4 is applied to study the relation
      between the molecular weight and the zero shear viscosity eta0 for high molecular
      weight HDPE. It was found that the zero shear viscosity values predicted from
      HTAF4 results are in good qualitative agreement with measured values obtained
      from dynamic mechanical spectroscopy (DMS) experiments, whereas eta0 values
      predicted from HTSEC do not show a strong correlation. The low molecular weight
      cutoff of HTAF4 is approximately 5x10(4) as a result of relatively large pores in
      the HTAF4 channel membrane. HTAF4 is, therefore, currently not suited to analyze
      low molecular weight materials.

PMID- 17442327
TI  - Ultratrace liquid chromatography/mass spectrometry analysis of large peptides
      with post-translational modifications using narrow-bore poly(styrene
      divinylbenzene) monolithic columns and extended range proteomic analysis.
AB  - This paper describes approaches to optimize the chromatographic performance for
      our recently developed LC-MS platform, extended range proteomic analysis (ERPA),
      for comprehensive protein characterization at the ultratrace level. Large
      digested peptide fragments up to 10 kDa (e.g., from lysyl endopeptidase
      digestion) with or without modifications were well separated with high resolution
      using narrow bore (20 and 50 microm I.D.) poly(styrene-divinylbenzene) (PS-DVB)
      monolithic columns constructed by in situ solution polymerization. Importantly,
      the macroporous structure of the monolithic columns facilitated mass transport of
      large peptides with improved recovery relative to small pore size reversed-phase
      packings. High sequence coverage (>95%), including identification of
      phosphorylated and glycosylated particles was achieved for beta-casein and
      epidermal growth factor receptor (EGFR) at the 4 and 20 fmol levels per
      injection, respectively, using the 20 microm I.D. PS-DVB monolithic column. For
      peptides with greater ionization efficiency, the detection limit could be lowered
      to approximately 400 zmol. Typically, the separation system produced a peak
      capacity of approximately 200 for a 10 cm column. This paper demonstrates that
      narrow-bore monolithic columns are suitable for high sensitivity and high
      resolution separation of large peptide fragments by LC-MS analysis.

PMID- 17442328
TI  - Dual-cloud point extraction as a preconcentration and clean-up technique for
      capillary electrophoresis speciation analysis of mercury.
AB  - A novel dual-cloud point extraction (dCPE) technique is proposed in this paper
      for the sample pretreatment of capillary electrophoresis (CE) speciation analysis
      of mercury. In dCPE, cloud point was carried out twice in a sample pretreatment.
      First, four mercury species, methylmercury (MeHg), ethylmercury (EtHg),
      phenylmercury (PhHg), and inorganic mercury (Hg(II)) formed hydrophobic complexes
      with 1-(2-pyridylazo)-2-naphthol (PAN). After heating and centrifuging, the
      complexes were extracted into the formed Triton X-114 surfactant-rich phase.
      Instead of the direct injection or analysis, the surfactant-rich phase containing
      the four Hg species was treated with 150 microL 0.1% (m/v) l-cysteine aqueous
      solution. The four Hg species were then transferred back into aqueous phase by
      forming hydrophilic Hg-l-cysteine complexes. After dCPE, the aqueous phase
      containing the Hg-l-cysteine complexes was subjected into electrophoretic
      capillary for mercury speciation analysis. Because the concentration of Triton X
      114 in the extract after dCPE was only around critical micelle concentration, the
      adsorption of surfactant on the capillary wall and its possible influence on the
      sample injection and separation in traditional CPE were eliminated. Plus, the
      hydrophobic interfering species were removed thoroughly by using dCPE resulted in
      significant improvement in analysis selectivity. Using 10 mL sample, 17, 15, 45,
      and 52 of preconcentration factors for EtHg, MeHg, PhHg, and Hg(II) were
      obtained. With CE separation and on-line UV detection, the detection limits were
      45.2, 47.5, 4.1, and 10.0 microg L(-1) (as Hg) for EtHg, MeHg, PhHg, and Hg(II),
      respectively. As an analysis method, the present dCPE-CE with UV detection
      obtained similar detection limits as of some CE-inductively coupled plasma mass
      spectrometry (ICPMS) hyphenation technique, but with simple instrumental setup
      and obviously low costs. Its utilization for Hg speciation was validated by the
      analysis of the spiked natural water and tilapia muscle samples.

PMID- 17442329
TI  - Fast determination of conditions for maximum dynamic capacity in cation-exchange
      chromatography of human monoclonal antibodies.
AB  - Dynamic binding capacity (DBC) measurements of cation-exchange resins were
      performed with two human monoclonal antibodies. DBC showed a pH dependent
      maximum, which was shifted to lower pH values with increasing buffer
      concentrations and increasing salting-out effect of the buffer anion according to
      the Hofmeister series. As this downshift correlates well with zeta potential
      values, a measurement of the latter allows the determination of the pH value for
      maximum DBC under a given set of conditions. Thus, the use of zeta potential
      values can accelerate the purification process development and helps to
      understand the protein adsorption mechanism.

PMID- 17442330
TI  - An investigation of the surface-enhanced Raman scattering effect from new
      substrates of several kinds of nanowire arrays.
AB  - Silver, titanium, nickel, and aluminum nanowire arrays with diameters from 90 to
      110 nm were prepared on AAO templates by laser molecular beam epitaxy. On the
      several kinds of nanowire arrays, high-quality surface-enhanced Raman scattering
      (SERS) spectra of probe molecules of the red dye Sudan II (C(18)H(16)N(2)O) were
      obtained. In particular, the SERS spectrum of Sudan II on an aluminum nanowire
      array is reported for the first time.

PMID- 17442331
TI  - Adsorption behaviors of high-valence metal ions on desferrioxamine B
      immobilization nylon 6,6 chelate fiber under highly acidic conditions.
AB  - Adsorption behaviors of the high-valence metal ions Zr(IV), Hf(IV), Ti(IV), V(V),
      Nb(V), Ta(V), and Mo(IV) on desferrioxamine B (DFB) immobilization nylon 6,6
      chelate fiber was investigated under highly acidic conditions. Though the
      complexes of DFB and the high-valence metal ions were extracted without
      selectivity by solvent extraction, the only zirconium ions showed higher
      adsorption percentages than that of other high-valence metal ions on the DFB
      immobilization nylon 6,6 chelate fiber. Adsorption properties were caused that
      limited the freedom of DFB by chemical immobilization. Especially, hafnium ions
      and zirconium ions, which have similar chemical properties, showed different
      adsorption behavior in highly acidic aqueous solutions. Zirconium ions were
      quantitatively adsorbed up to 13.5 micromol/g.

PMID- 17442332
TI  - Electrokinetically-driven flow mixing in microchannels with wavy surface.
AB  - This paper investigates the mixing characteristics of electrokinetically-driven
      flow in microchannels with different wavy surface configurations. Numerical
      simulations are performed to analyze the influence of the wave amplitude and the
      length of the wavy section on the mixing efficiency within the microchannel.
      Typically, straight channels have a poor mixing performance because the fluid
      flow is restricted to the low Reynolds number regime, and hence mixing takes
      place primarily as a result of diffusion effects. However, the wavy surfaces
      employed in the current microchannels increase the interfacial contact area
      between the two species in the microchannel and therefore improve the mixing
      efficiency. The mixing performance is further enhanced by the application of a
      heterogeneous charge pattern on the wavy surfaces. The numerical results show
      that the heterogeneous charge pattern generates flow circulations near the
      microchannel walls. These circulations are shown to provide an effective
      enhancement in the mixing performance. Overall, the present results show that the
      mixing performance is improved by increasing the magnitude of the heterogeneous
      surface zeta potential upon the wavy surface or by increasing the wave amplitude
      or the length of the wavy section in the microchannel.

PMID- 17442333
TI  - Studies of the equilibrium and thermodynamics of the adsorption of Cu(2+) onto as
      produced and modified carbon nanotubes.
AB  - This study evaluates the Cu(2+) adsorption efficiency of as-produced carbon
      nanotubes (CNTs) and those modified by HNO(3) and NaOCl. The surface area,
      pH(pzc), pore volume, FTIR analyses, and average pore size of CNTs were
      determined to compare the differences between nanotubes before and after HNO(3)
      and NaOCl modification. The HNO(3) and NaOCl modifications increased the pore
      volume and the average pore size of CNTs; in contrast, the pH(pzc) was decreased.
      The modification processes produced some functional groups. The adsorption
      capacity of Cu(2+) on as-produced and modified CNTs increased with the pH and
      temperature; however, the effects of the ionic strength on the adsorption of
      Cu(2+) on as-produced and modified CNTs were negligible. The linear correlation
      coefficients of Langmuir and Freundlich isotherms were obtained and the results
      revealed that the Langmuir isotherm fitted the experimental results better than
      did the Freundlich isotherm. The adsorption capacity of Cu(2+) followed the order
      NaOCl-modified CNTs > HNO(3)-modified CNTs > as-produced CNTs. Changes in the
      free energy of adsorption (DeltaG(o)), enthalpy (DeltaH(o)), and entropy
      (DeltaS(o)) were determined. All DeltaG(o) values were negative; the DeltaH(o)
      values of as-produced, HNO(3)-modified, and NaOCl-modified CNTs were 10.84,
      17.08, and 67.77 kJ/mol and the DeltaS(o) values were 96.89, 122.88, and 319.76
      J/mol K, respectively.

PMID- 17442334
TI  - Effect of ex vivo storage and Cyto-Chex on the expression of P-selectin
      glycoprotein ligand-1 (PSGL-1) on human peripheral leukocytes.
AB  - P-selectin glycoprotein ligand-1 (PSGL-1) is expressed on leukocytes and its
      expression is elevated in asthma and chronic obstructive pulmonary disease. This
      study assessed whether the cell stabilisation solution Cyto-Chex is able to
      preserve such quantitative differences for delayed testing. Peripheral blood was
      mixed with Cyto-Chex and stored refrigerated or at ambient temperature. Aliquots
      were tested by flow cytometry 2 to 168 h after collection for PSGL-1, CD3, CD4,
      CD8, and CD16 expression and marker-positive cell counts. Compared with controls
      a marked reduction of staining intensities is seen at all time points for all
      markers, irrespective of the storage temperature. This loss of bright staining
      did not or only moderately decrease marker-positive cell counts except for PSGL
      1+ lymphocytes which declined in parallel with staining intensity. These findings
      indicate that Cyto-Chex is not able to preserve the expression or affinity to
      antibodies of surface markers to allow delayed determination of quantitative
      differences or detection of weakly staining cells. Immunophenotyping is mostly
      possible for 7 days after collection, however, this has to be tested for each
      marker and cell type of interest.

PMID- 17442335
TI  - Production and characterization of monoclonal antibodies against complexes of the
      NKT cell ligand alpha-galactosylceramide bound to mouse CD1d.
AB  - The alpha-galactosylceramide (alpha-GalCer) known as KRN7000 remains the best
      studied ligand of the lipid-binding MHC class I-like protein CD1d. The
      KRN7000:CD1d complex is highly recognized by invariant natural killer T (iNKT)
      cells, an evolutionarily conserved subset of T lymphocytes that express an
      unusual semi-invariant T cell antigen receptor, and mediate a variety of
      proinflammatory and immunoregulatory functions. To facilitate the study of
      glycolipid antigen presentation to iNKT cells by CD1d, we undertook the
      production of mouse monoclonal antibodies (mAbs) specific for complexes of
      KRN7000 bound to mouse CD1d (mCD1d) proteins. Three such monoclonal antibodies
      were isolated that bound only to mCD1d proteins that were loaded with KRN7000 or
      closely-related forms of alpha-GalCer. These mAbs showed no reactivity with mCD1d
      proteins that were not loaded with alpha-GalCer, nor did they bind to complexes
      formed by loading mCD1d with the self-glycolipid and putative iNKT cell ligand
      isoglobotrihexosylceramide. These complex-specific monoclonal antibodies allow
      the direct detection and monitoring of complexes formed by the binding of KRN7000
      and other alpha-GalCer analogues to mCD1d. The availability of these mAbs should
      facilitate a wide range of studies on the biology and potential clinical
      applications of CD1d-restricted iNKT cells.

PMID- 17442336
TI  - Autocrine activation of ecdysteroidogenesis in the prothoracic glands of the
      silkworm, Bombyx mori.
AB  - Ecdysteroidogenesis in the prothoracic glands is activated by the neuropeptide,
      prothoracicotropic hormone (PTTH). The present study demonstrates autocrine
      activation of ecdysteroidogenesis in prothoracic glands of the silkworm, Bombyx
      mori. Using both a long-term in vitro organ culture system and an ecdysteroid
      radioimmunoassay, it was found that either decreasing the incubation volume, from
      100 to 5 microl, or increasing the number of glands incubated per drop (50
      microl) from 1 to 5 significantly increased ecdysteroid secretion. Prothoracic
      gland-conditioned medium was used to clarify the autocrine factor. The results
      showed that activation of ecdysteroidogenesis by the prothoracic gland
      conditioned medium appeared to be dose dependent and a dramatic increase in
      ecdysteroid secretion was observed after 6h of incubation in the conditioned
      medium. Moreover, it appeared that autocrine activation occurred when glands were
      incubated in large volumes of incubation medium and during a short incubation
      period, indicating that the factor may exert its action in situ at some specific
      developmental stages. This tropic factor was further characterized, and it was
      found that the factor seemed to be heat-stable, with a molecular weight estimated
      to be between 1000 and 3000 Da. Injection of the concentrated putative autocrine
      factor into day 5 last instar larvae greatly increased ecdysteroidogenic activity
      of the prothoracic glands compared to those injected with saline, indicating the
      possible in vivo function of the present factor.

PMID- 17442338
TI  - Mouse 17alpha-hydroxysteroid dehydrogenase (AKR1C21) binds steroids differently
      from other aldo-keto reductases: identification and characterization of amino
      acid residues critical for substrate binding.
AB  - The mouse 17alpha-hydroxysteroid dehydrogenase (m17alpha-HSD) is the unique known
      member of the aldo-keto reductase (AKR) superfamily able to catalyze efficiently
      and in a stereospecific manner the conversion of androstenedione (Delta4) into
      epi-testosterone (epi-T), the 17alpha-epimer of testosterone. Structural and
      mutagenic studies had already identified one of the residues delineating the
      steroid-binding cavity, A24, as the major molecular determinant for the
      stereospecificity of m17alpha-HSD. We report here a ternary complex crystal
      structure (m17alpha-HSD:NADP(+):epi-T) determined at 1.85 A resolution that
      confirms this and reveals a unique steroid-binding mode for an AKR enzyme.
      Indeed, in addition to the interactions found in all other AKRs (van der Waals
      contacts stabilizing the core of the steroid and the hydrogen bonds established
      at the catalytic site by the Y55 and H117 residues with the oxygen atom of the
      ketone group to be reduced), m17alpha-HSD establishes with the other extremity of
      the steroid nucleus an additional interaction involving K31. By combining direct
      mutagenesis and kinetic studies, we found that the elimination of this hydrogen
      bond did not affect the affinity of the enzyme for its steroid substrate but led
      to a slight but significant increase of its catalytic efficiency (k(cat)/K(m)),
      suggesting a role for K31 in the release of the steroidal product at the end of
      the reaction. This previously unobserved steroid-binding mode for an AKR is
      similar to that adopted by other steroid-binding proteins, the hydroxysteroid
      dehydrogenases of the short-chain dehydrogenases/reductases (SDR) family and the
      steroid hormone nuclear receptors. Mutagenesis and structural studies made on the
      human type 3 3alpha-HSD, a closely related enzyme that shares 73% amino acids
      identity with the m17alpha-HSD, also revealed that the residue at position 24 of
      these two enzymes directly affects the binding and/or the release of NADPH, in
      addition to its role in their 17alpha/17beta stereospecificity.

PMID- 17442337
TI  - Sarcolipin and phospholamban as regulators of cardiac sarcoplasmic reticulum Ca2+
      ATPase.
AB  - The cardiac sarcoplasmic reticulum calcium ATPase (SERCA2a) plays a critical role
      in maintaining the intracellular calcium homeostasis during cardiac contraction
      and relaxation. It has been well documented over the years that altered
      expression and activity of SERCA2a can lead to systolic and diastolic
      dysfunction. The activity of SERCA2a is regulated by two structurally similar
      proteins, phospholamban (PLB) and sarcolipin (SLN). Although, the relevance of
      PLB has been extensively studied over the years, the role SLN in cardiac
      physiology is an emerging field of study. This review focuses on the advances in
      the understanding of the regulation of SERCA2a by SLN and PLB. In particular, it
      highlights the similarities and differences between the two proteins and their
      roles in cardiac patho-physiology.

PMID- 17442339
TI  - Erythroid Kruppel-like factor regulates the G1 cyclin dependent kinase inhibitor
      p18INK4c.
AB  - Erythroid Kruppel-like factor (EKLF, KLF1) is an essential erythroid cell
      specific C(2)H(2) zinc finger transcription factor that binds CACC box elements
      in promoters and distant regulatory elements to activate transcription. Forced
      expression of EKLF arrests cell division. The cyclin dependent kinase (Cdk)
      inhibitor p18(INK4c) was identified as a potential novel EKLF target gene from an
      expression profiling study. The p18(INK4c) protein functions as an inhibitor of
      Cdk4 and Cdk6 activity during early G1 phase of the cell cycle, thus acting as a
      physiological brake on cell division. We confirmed p18(INK4c) is downregulated in
      EKLF null mice by real-time PCR and Western blotting, and identified three
      closely associated and highly conserved EKLF binding sites (CCNCNCCCN)
      approximately 1 kb upstream of the p18(INK4c) transcriptional start site. We
      showed that EKLF binds to one of these elements by gel shift assay and
      demonstrated this site is capable of driving EKLF dependent transcription. We
      also determined by chromatin immunoprecipitation (ChIP) that this region of the
      p18(INK4c) promoter is bound by EKLF in erythroid cells. Thus, EKLF is a direct
      regulator of p18(INK4c) gene expression, and much of EKLF's role in driving
      erythroid cell differentiation may occur via p18(INK4c).

PMID- 17442340
TI  - Functional and structural role of amino acid residues in the odd-numbered
      transmembrane alpha-helices of the bovine mitochondrial oxoglutarate carrier.
AB  - The mitochondrial oxoglutarate carrier (OGC) plays an important role in the
      malate-aspartate shuttle, the oxoglutarate-isocitrate shuttle and
      gluconeogenesis. To establish amino acid residues that are important for
      function, each residue in the transmembrane alpha-helices H1, H3 and H5 was
      replaced systematically by a cysteine in a fully functional mutant carrier that
      was devoid of cysteine residues. The transport activity of the mutant carriers
      was measured in the presence and absence of sulfhydryl reagents. The observed
      effects were rationalized by using a comparative structural model of the OGC.
      Most of the residues that are critical for function are found at the bottom of
      the cavity and they belong to the signature motifs P-X-[DE]-X-X-[KR] that form a
      network of three inter-helical salt bridges that close the carrier at the matrix
      side. The OGC deviates from most other carriers, because it has a conserved
      leucine (L144) rather than a positively charged residue in the signature motif of
      the second repeat and thus the salt bridge network is lacking one salt bridge.
      Incomplete salt-bridge networks due to hydrophobic, aromatic or polar
      substitutions are observed in other dicarboxylate, phosphate and adenine
      nucleotide transporters. The interaction between the carrier and the substrate
      has to provide the activation energy to trigger the re-arrangement of the salt
      bridge network and other structural changes required for substrate translocation.
      For substrates such as malate, which has only two carboxylic and one hydroxyl
      group, a reduction in the number of salt bridges in the network may be required
      to lower the energy barrier for translocation. Another group of key residues,
      consisting of T36, A134, and T233, is close to the putative substrate binding
      site and substitutions or modifications of these residues may interfere with
      substrate binding and ion coupling. Residues G32, A35, Q40, G130, G133, A134,
      G230, and S237 are potentially engaged in inter-helical interactions and they may
      be involved in the movements of the alpha-helices during translocation.

PMID- 17442342
TI  - Analyzing the "degree of humanness" of antibody sequences.
AB  - Genetically engineered mouse antibodies are now commonly in clinical use.
      However, their development is limited because the human immune system tends to
      regard them as foreign and this triggers an immune response. The solution is to
      make engineered antibodies appear more human. Here, we propose a method to assess
      the "degree of humanness" of antibody sequences providing a tool that may
      contribute to predictions of antigenicity. We analyzed sequences of antibodies
      belonging to various chains/classes in human and mouse. Our analysis of metrics
      based on percentage sequence identity between antibody sequences shows distinct
      differences between human and mouse sequences. Based on mean sequence identity
      and standard deviation, we calculated Z-scores for data sets of antibody
      sequences extracted from the Kabat database. We applied the analysis to a set of
      humanized and chimeric antibodies and to human germline sequences. We conclude
      that this approach may aid in the selection of more suitable mouse variable
      domains for antibody engineering to render them more human but in general, we
      find that typicality of a sequence compared with the expressed human repertoire
      is not well correlated with antigenicity. We have provided a Web server allowing
      humanness to be assigned for a sequence.

PMID- 17442341
TI  - Crystal structure of the cofactor-binding domain of the human phase II drug
      metabolism enzyme UDP-glucuronosyltransferase 2B7.
AB  - Human UDP-glucuronosyltransferases (UGT) are the dominant phase II conjugative
      drug metabolism enzymes that also play a central role in processing a range of
      endobiotic compounds. UGTs catalyze the covalent addition of glucuronic acid
      sugar moieties to a host of therapeutics and environmental toxins, as well as to
      a variety of endogenous steroids and other signaling molecules. We report the 1.8
      A resolution apo crystal structure of the UDP-glucuronic acid binding domain of
      human UGT isoform 2B7 (UGT2B7), which catalyzes the conjugative elimination of
      opioid, antiviral, and anticancer drugs. This is the first crystal structure of
      any region of a mammalian UGT drug metabolism enzyme. Designated UGT2B7 mutants
      at residues predicted to interact with the UDP-glucuronic acid cofactor exhibited
      significantly impaired catalytic activity, with maximum effects observed for
      amino acids closest to the glucuronic acid sugar transferred to the acceptor
      molecule. Homology modeling of UGT2B7 with related plant flavonoid
      glucosyltransferases indicates human UGTs share a common catalytic mechanism.
      Point mutations at predicted catalytic residues in UGT2B7 abrogated activity,
      strongly suggesting human UGTs also utilize a serine hydrolase-like catalytic
      mechanism to facilitate glucuronic acid transfer.

PMID- 17442343
TI  - The contribution of the zinc-finger motif to the function of Thermus thermophilus
      ribosomal protein S14.
AB  - In the crystal structure of the 30S ribosomal subunit from Thermus thermophilus,
      cysteine 24 of ribosomal protein S14 (TthS14) occupies the first position in a
      CXXC-X12-CXXC motif that coordinates a zinc ion. The structural and functional
      importance of cysteine 24, which is widely conserved from bacteria to humans, was
      studied by its replacement with serine and by incorporating the resulting mutant
      into Escherichia coli ribosomes. The capability of such modified ribosomes in
      binding tRNA at the P and A-sites was equal to that obtained with ribosomes
      incorporating wild-type TthS14. In fact, both chimeric ribosomal species
      exhibited 20% lower tRNA affinity compared with native E. coli ribosomes. In
      addition, replacement of the native E. coli S14 by wild-type, and particularly by
      mutant TthS14, resulted in reduced capability of the 30S subunit for association
      with 50S subunits. Nevertheless, ribosomes from transformed cells sedimented
      normally and had a full complement of proteins. Unexpectedly, the peptidyl
      transferase activity in the chimeric ribosomes bearing mutant TthS14 was much
      lower than that measured in ribosomes incorporating wild-type TthS14. The
      catalytic center of the ribosome is located within the 50S subunit and,
      therefore, it is unlikely to be directly affected by changes in the structure of
      S14. More probably, the perturbing effects of S14 mutation on the catalytic
      center seem to be propagated by adjacent intersubunit bridges or the P-site tRNA
      molecule, resulting in weak donor-substrate reactivity. This hypothesis was
      verified by molecular dynamics simulation analysis.

PMID- 17442344
TI  - DNA polymerase switching on homotrimeric PCNA at the replication fork of the
      euryarchaea Pyrococcus abyssi.
AB  - DNA replication in Archaea, as in other organisms, involves large protein
      complexes called replisomes. In the Euryarchaeota subdomain, only two putative
      replicases have been identified, and their roles in leading and lagging strand
      DNA synthesis are still poorly understood. In this study, we focused on the
      coupling of proliferating cell nuclear antigen (PCNA)-loading mechanisms with DNA
      polymerase function in the Euryarchaea Pyrococcus abyssi. PCNA spontaneously
      loaded onto primed DNA, and replication factor C dramatically increased this
      loading. Surprisingly, the family B DNA polymerase (Pol B) also increased PCNA
      loading, probably by stabilizing the clamp on primed DNA via an essential motif.
      In contrast, on an RNA-primed DNA template, the PCNA/Pol B complex was
      destabilized in the presence of dNTPs, allowing the family D DNA polymerase (Pol
      D) to perform RNA-primed DNA synthesis. Then, Pol D is displaced by Pol B to
      perform processive DNA synthesis, at least on the leading strand.

PMID- 17442345
TI  - Crystal structure of the Marasmius oreades mushroom lectin in complex with a
      xenotransplantation epitope.
AB  - MOA, a lectin from the mushroom Marasmius oreades, is one of the few reagents
      that specifically agglutinate blood group B erythrocytes. Further, it is the only
      lectin known to have exclusive specificity for Galalpha(1,3)Gal-containing sugar
      epitopes, which are antigens that pose a severe barrier to animal-to-human organ
      transplantation. We describe here the structure of MOA at 2.4 A resolution, in
      complex with the linear trisaccharide Galalpha(1,3)Galbeta(1,4)GlcNAc. The
      structure is dimeric, with two distinct domains per protomer: the N-terminal
      lectin module adopts a ricinB/beta-trefoil fold and contains three putative
      carbohydrate-binding sites, while the C-terminal domain serves as a dimerization
      interface. This latter domain, which has an unknown function, reveals a novel
      fold with intriguing conservation of an active site cleft. A number of
      indications suggest that MOA may have an enzymatic function in addition to the
      sugar-binding properties.

PMID- 17442346
TI  - Fluorescence correlation spectroscopic study of serpin depolymerization by
      computationally designed peptides.
AB  - Members of the serine proteinase inhibitor (serpin) family play important roles
      in the inflammatory and coagulation cascades. Interaction of a serpin with its
      target proteinase induces a large conformational change, resulting in insertion
      of its reactive center loop (RCL) into the main body of the protein as a new
      strand within beta-sheet A. Intermolecular insertion of the RCL of one serpin
      molecule into the beta-sheet A of another leads to polymerization, a widespread
      phenomenon associated with a general class of diseases known as serpinopathies.
      Small peptides are known to modulate the polymerization process by binding within
      beta-sheet A. Here, we use fluorescence correlation spectroscopy (FCS) to probe
      the mechanism of peptide modulation of alpha(1)-antitrypsin (alpha(1)-AT)
      polymerization and depolymerization, and employ a statistical computationally
      assisted design strategy (SCADS) to identify new tetrapeptides that modulate
      polymerization. Our results demonstrate that peptide-induced depolymerization
      takes place via a heterogeneous, multi-step process that begins with internal
      fragmentation of the polymer chain. One of the designed tetrapeptides is the most
      potent antitrypsin depolymerizer yet found.

PMID- 17442347
TI  - Role of spinal voltage-dependent calcium channel alpha 2 delta-1 subunit in the
      expression of a neuropathic pain-like state in mice.
AB  - The present study was undertaken to investigate the role of spinal voltage
      dependent calcium channel alpha(2)delta-1 subunit in the expression of a
      neuropathic pain-like state induced by partial sciatic nerve ligation in mice. In
      cultured spinal neurons, gabapentin (GBP), which displays the inhibitory effect
      of alpha(2)delta-1 subunit, suppressed the extracellular Ca(2+) influx induced by
      KCl, whereas it failed to inhibit the intracellular Ca(2+) release induced by
      inositol-1,4,5-triphosphate. Seven days after sciatic nerve ligation, the protein
      level of alpha(2)delta-1 subunit in the ipsilateral spinal cord was clearly
      increased compared to that observed in sham-operated mice. In addition, the mRNA
      level of alpha(2)delta-1 subunit was significantly increased in the dorsal root
      ganglion, but not in the spinal cord, of nerve-ligated mice. Under these
      conditions, a marked decrease in the latency of paw-withdrawal against a thermal
      stimulation and tactile stimulation, induced by sciatic nerve ligation was
      abolished by repeated intrathecal (i.t.) treatment with GBP. Additionally, the
      persistent reduction in the nociceptive threshold by i.t. treatment with GBP at
      the early stage of the neuropathic pain-like state was maintained for 7 days even
      after GBP withdrawal. It is of interest to note that a single i.t. post-injection
      of GBP showed a marked and transient inhibitory effect on the developed
      neuropathic pain-like state, whereas repeated i.t. post-treatment with GBP
      produced a persistent inhibitory effect during the treatment. In conclusion, we
      propose here that the neuropathic pain-like state with sciatic nerve ligation is
      associated with the increased level of the alpha(2)delta-1 subunit of Ca(2+)
      channels at the sensory nerve terminal in the spinal dorsal horn of mice.
      Furthermore, the present data provide evidence that the neuropathic pain may be
      effectively controlled by repeated treatment with GBP at the early stage.

PMID- 17442348
TI  - In vitro genotoxicity of PAH mixtures and organic extract from urban air
      particles part I: acellular assay.
AB  - Acellular assay of calf thymus DNA+/-rat liver microsomal S9 fraction coupled
      with (32)P-postlabelling was used to study the genotoxic potential of organic
      compounds bound onto PM10 particles collected in three European cities-Prague
      (CZ), Kosice (SK) and Sofia (BG) during summer and winter periods. B[a]P alone
      induced DNA adduct levels ranging from 4.8 to 768 adducts/10(8) nucleotides in
      the concentration dependent manner. However, a mixture of 8 c-PAHs with equimolar
      doses of B[a]P induced 3.7-757 adducts/10(8) nucleotides, thus suggesting the
      inhibition of DNA adduct forming activity by interaction among various PAHs.
      Comparison of DNA adduct levels induced by various EOMs indicates higher
      variability among seasons than among localities. DNA adduct levels for Prague
      collection site varied from 19 to 166 adducts/10(8) nucleotides, for Kosice from
      22 to 85 and for Sofia from 6 to 144 adducts/10(8) nucleotides. Bioactivation
      with S9 microsomal fraction caused 2- to 7-fold increase in DNA adduct levels
      compared to -S9 samples, suggesting a crucial role of indirectly acting genotoxic
      EOM components, such as PAHs. We have demonstrated for the first time a
      significant positive correlation between B[a]P content in EOMs and total DNA
      adduct levels detected in the EOM treated samples (R=0.83; p=0.04). These results
      suggest that B[a]P content in EOM is an important factor for the total genotoxic
      potential of EOM and/or B[a]P is a good indicator of the presence of other
      genotoxic compounds causing DNA adducts. Even stronger correlation between the
      content of genotoxic compounds in EOMs and total DNA adduct levels detected
      (R=0.94; p=0.005) was found when eight c-PAHs were taken into the consideration.
      Our findings support a hypothesis that a relatively limited number of EOM
      components is responsible for a major part of its genotoxicity detectable as DNA
      adducts by (32)P-postlabelling.

PMID- 17442349
TI  - Flavonoids and isoflavonoids from Gynerium sagittatum.
AB  - Four flavonoids namely (2R,3R)-2,3-trans-7,4'-dimethoxydihydroflavonol,
      (2R,3S,4S)-2,3-trans-3,4-cis-7,4'-dimethoxy-3,4-flavandiol, 6-hydroxy-7,4'
      dimethoxyflavone, 6,7,4'-trimethoxyflavone, along with the known isoflavonoids
      ferreirin, dihydrocajanin, dalbergioidin, dihydrobiochanin A and biochanin A and
      other 11 known compounds were isolated from the roots of Gynerium sagittatum. The
      structural characterization of these compounds was carried out via one- and two
      dimensional NMR experiments in combination with ESI-MS. Finally a quantitative
      analysis of the isoflavones of the methanolic extract was performed by LC-ESI-MS.
      The high quantity of isoflavonoids found in G. sagittatum makes this plant a good
      natural source of isoflavonoids.

PMID- 17442350
TI  - Cucurbitacins from Bacopa monnieri.
AB  - Four cucurbitacins, bacobitacin A-D (1-4) as well as, a known cytotoxic,
      cucurbitacin E (5) together with three known phenylethanoid glycosides,
      monnieraside I, III and plantioside B were isolated form the aerial part of
      Bacopa monnieri. Their structures were elucidated on the basis of extensive
      spectroscopic investigations (1D, 2D NMR and ESI-QTOF-MS/MS). This is the first
      report on the characterization of cucurbitacins in B. monnieri.

PMID- 17442351
TI  - Diagnosis of canine brucellosis by ELISA using an antigen obtained from wild
      Brucella canis.
AB  - An indirect ELISA test was developed for the diagnosis of Brucella canis
      infection in dogs. A bacterial whole cell extract was used as a solid phase
      antigen, using B. canis isolated from an infected animal. Sera from culture
      positive and healthy negative animals were used as internal reference controls.
      The cut-off point was determined by a mathematical formula for a statistically
      valid value, which defined the upper prediction limit, based on the upper tail of
      the t-distribution of 21 negative control sera readings, for the confidence level
      of 99.5%. The sensitivity and specificity of the ELISA test were 95% and 91%,
      respectively. The ELISA test showed a significant concordance index (K=0.84) with
      the agar gel immunodiffusion test. The reliability of the ELISA for the detection
      of infected animals was established by a double blind study testing 280 sera
      provided by serum banks from different diagnostic and research institutions and
      analyzed by ROC Curve.

PMID- 17442353
TI  - Multicentre survey of incidence and public health impact of leptospirosis in the
      Western Pacific.
AB  - The objectives of the study were to describe the mode of circulation (endemic or
      epidemic) of human leptospirosis in various Pacific island states and territories
      by identifying predominant Leptospira serogroups and the most probable routes of
      human exposure, and to recommend a feasible laboratory strategy for leptospirosis
      in the Pacific. From September 2003 to December 2005, 263 leptospirosis suspect
      patients were recruited by public practitioners on 11 Pacific islands, using the
      WHO case definition. Diagnosis was confirmed using a three-level serology
      algorithm and a regional laboratory network. Sixty-nine leptospirosis cases were
      identified from seven islands: Futuna, Raiatea and the Marquesas Islands where
      outbreaks were apparent, and Vanuatu, Fiji, Palau and Wallis where sporadic cases
      indicated at least the presence of the disease. Most patients were men aged 17-40
      years. The infection appeared to occur during the course of normal daily
      activities more often than following specific professional exposure. The dominant
      presumptive serogroups were Icterohaemorrhagiae and Australis, highly suggestive
      of a rodent reservoir. This study confirms the widespread presence of
      leptospirosis in the Pacific region. It should help in the implementation of
      local leptospirosis control plans and highlights the role of on-site laboratory
      confirmation.

PMID- 17442352
TI  - Correlation between the components of the insulin-like growth factor I system,
      nutritional status and visceral leishmaniasis.
AB  - The role of the insulin-like growth factor I (IGF-I) system and nutritional
      status was studied in 241 children from a Brazilian area endemic for visceral
      leishmaniasis (VL). Thirty-nine children had the active form, 20 were
      oligosymptomatic, 38 were asymptomatic and 144 were not infected. Serum
      concentrations of growth hormone (GH), total and free IGF-I and IGF binding
      protein 3 (IGFBP3) were measured by radioimmunoassay. Nutritional status was
      evaluated by anthropometric indicators and biochemical measurements. Total and
      free IGF-I and IGFBP3 were significantly reduced in the active form. Z scores for
      total and free IGF-I and for IGFBP3 were found to be significantly lower for
      active VL and oligosymptomatic individuals than for asymptomatic individuals, but
      never reached values <or=2 SD. Median values of weight-for-age Z and height-for
      age Z (HAZ) scores and albumin concentration were significantly different in the
      active VL group compared with the other groups. Multiple discriminant analysis
      selected albumin and HAZ score as predictors of active and oligosymptomatic VL.
      The lack of correlation between auxological data and serum concentrations of the
      GH/IGF axis components suggested that the primary cause of retarded growth in
      children with active VL is not dependent on IGF-I or IGFBP3, but rather on VL
      intrinsic factors that might secondarily involve the GH/IGF axis.

PMID- 17442354
TI  - Brucellosis as a cause of acute febrile illness in Egypt.
AB  - To develop better estimates of brucellosis incidence, we conducted population
      based surveillance for acute febrile illness (AFI) in Fayoum governorate
      (population 2347249), Egypt during two summer periods (2002 and 2003). All
      hospitals and a representative sample of community healthcare providers were
      included. AFI patients without obvious etiology were tested for brucellosis by
      culture and serology. Incidence estimates were calculated adjusting for sampling
      methodology and study period. Of 4490 AFI patients enrolled, 321 (7%) met the
      brucellosis case definition. The estimated annual incidence of brucellosis per
      100000 population was 64 and 70 in 2002 and 2003, respectively. The median age of
      brucellosis patients was 26 years and 70% were male; 53% were initially diagnosed
      as typhoid fever. Close contact with animals and consumption of unpasteurized
      milk products were associated with brucellosis. The high incidence of brucellosis
      in Fayoum highlights its public health importance, and the need to implement
      prevention strategies in humans and animals.

PMID- 17442355
TI  - The evolution of conformist transmission in social learning when the environment
      changes periodically.
AB  - Conformity is often observed in human social learning. Social learners
      preferentially imitate the majority or most common behavior in many situations,
      though the strength of conformity varies with the situation. Why has such a
      psychological tendency evolved? I investigate this problem by extending a
      standard model of social learning evolution with infinite environmental states
      (Feldman, M.W., Aoki, K., Kumm, J., 1996. Individual versus social learning:
      evolutionary analysis in a fluctuating environment. Anthropol. Sci. 104, 209-231)
      to include conformity bias. I mainly focus on the relationship between the
      strength of conformity bias that evolves and environmental stability, which is
      one of the most important factors in the evolution of social learning. Using the
      evolutionarily stable strategy (ESS) approach, I show that conformity always
      evolves when environmental stability and the cost of adopting a wrong behavior
      are small, though environmental stability and the cost of individual learning
      both negatively affect the strength of conformity.

PMID- 17442356
TI  - Damage segregation at fissioning may increase growth rates: a superprocess model.
AB  - A fissioning organism may purge unrepairable damage by bequeathing it
      preferentially to one of its daughters. Using the mathematical formalism of
      superprocesses, we propose a flexible class of analytically tractable models that
      allow quite general effects of damage on death rates and splitting rates and
      similarly general damage segregation mechanisms. We show that, in a suitable
      regime, the effects of randomness in damage segregation at fissioning are
      indistinguishable from those of randomness in the mechanism of damage
      accumulation during the organism's lifetime. Moreover, the optimal population
      growth is achieved for a particular finite, non-zero level of combined randomness
      from these two sources. In particular, when damage accumulates deterministically,
      optimal population growth is achieved by a moderately unequal division of damage
      between the daughters, while too little or too much division is sub-optimal.
      Connections are drawn both to recent experimental results on inheritance of
      damage in protozoans, and to theories of aging and resource division between
      siblings.

PMID- 17442357
TI  - Nitric oxide and bcl-2 mediated the apoptosis induced by nickel(II) in human T
      hybridoma cells.
AB  - Although effects of nickel(II) on the immune system have long been recognized,
      little is known about the effects of nickel(II) on the induction of apoptosis and
      related signaling events in T cells. In the present study, we investigated the
      roles and signaling pathways of nickel(II) in the induction of apoptosis in a
      human T cell line jurkat. The results showed that the cytotoxic effects of Ni
      involved significant morphological changes and chromosomal condensation (Hoechst
      33258 staining). Analyses of hypodiploid cells and FITC-Annexin V and PI double
      staining showed significant increase of apoptosis in jurkat cells 6, 12 and 24 h
      after nickel(II) treatment. Flow cytometry analysis also revealed that the loss
      of mitochondrial membrane potential (MMP) occurred concomitantly with the onset
      of NiCl(2)-induced apoptosis. Induction of apoptotic cell death by nickel was
      mediated by reduction of bcl-2 expression. Furthermore, nickel stimulated the
      generation of nitric oxide (NO). These results suggest that nickel(II) chloride
      induces jurkat cells apoptosis via nitric oxide generation, mitochondrial
      depolarization and bcl-2 suppression.

PMID- 17442358
TI  - Lonidamine affects testicular steroid hormones in immature mice.
AB  - The effects on the hypothalamus-pituitary-testicular axis of the well-known
      antispermatogenic drug lonidamine (LND) has not been elucidated so far. In the
      present study, the possible changes of the testicular steroid hormones were
      evaluated in immature mice for a better characterization of the LND adverse
      effects both in its use as antitumoral agent and male contraceptive. Male CD1
      mice were orally treated on postnatal day 28 (PND28) with LND single doses (0 or
      100 mg/kg b.w.) and euthanized every 24 h from PND29 to PND32, on PND35 and on
      PND42 (1 and 2 weeks after the administration, respectively). Severe testicular
      effects were evidenced in the LND treated groups, including: a) significant
      testis weight increase, 24 h and 48 h after dosing; b) sperm head counts decrease
      (more than 50% of the control) on PND29-32; c) damage of the tubule morphology
      primarily on the Sertoli cell structure and germ cell exfoliation. All these
      reproductive endpoints were recovered on PND42. At the same time, a significant
      impairment of the testicular steroid balance was observed in the treated mice, as
      evidenced by the decrease of testosterone (T) and androstenedione (ADIONE) and
      the increase of 17OH-progesterone (17OH-P4) on the first days after dosing, while
      the testicular content of 17beta-estradiol (E2) was unchanged. The hormonal
      balance was not completely restored afterwards, as levels of T, ADIONE and 17OH
      P4 tended to be higher in the treated mice than in the controls, on PND35 and
      PND42. These data showed for the first time that LND affects intratesticular
      steroids in experimental animals. However further data are needed both to
      elucidate the mechanism responsible for the impairment of these metabolic
      pathways and to understand if the androgens decrease observed after LND
      administration could be partially involved in the testicular damage.

PMID- 17442359
TI  - Involvement of apoptotic cell death and cell cycle perturbation in retinoic acid
      induced cleft palate in mice.
AB  - Retinoic acid (RA), a metabolite of vitamin A, plays a key role in a variety of
      biological processes and is essential for normal embryonic development. On the
      other hand, exogenous RA could cause cleft palate in offspring when it is given
      to pregnant animals at either the early or late phases of palatogenesis, but the
      pathogenetic mechanism of cleft palate caused by excess RA remains not fully
      elucidated. The aim of the present study was to investigate the effects of excess
      of RA on early palatogenesis in mouse fetuses and analyze the teratogenic
      mechanism, especially at the stage prior to palatal shelf elevation. We gave all
      trans RA (100 mg/kg) orally to E11.5 ICR pregnant mice and observed the changes
      occurring in the palatal shelves of their fetuses. It was found that apoptotic
      cell death increased not only in the epithelium of the palatal shelves but also
      in the tongue primordium, which might affect tongue withdrawal movement during
      palatogenesis and impair the horizontal elevation of palatal shelves. In
      addition, RA was found to prevent the G(1)/S progression of palatal mesenchymal
      cells through upregulation of p21(Cip1), leading to Rb hypophospholylation. Thus,
      RA appears to cause G(1) arrest in palatal mesenchymal cells in a similar manner
      as in various cancer and embryonic cells. It is likely that apoptotic cell death
      and cell cycle disruption are involved in cleft palate formation induced by RA.

PMID- 17442362
TI  - Binocular influences on global motion processing in the human visual system.
AB  - This study investigates four key issues concerning the binocular properties of
      the mechanisms that encode global motion in human vision: (1) the extent of any
      binocular advantage; (2) the possible site of this binocular summation; (3)
      whether or not purely monocular inputs exist for global motion perception; (4)
      the extent of any dichoptic interaction. Global motion coherence thresholds were
      measured using random-dot-kinematograms as a function of the dot modulation depth
      (contrast) for translational, radial and circular flow fields. We found a marked
      binocular advantage of approximately 1.7, comparable for all three types of
      motion and the performance benefit was due to a contrast rather than a global
      motion enhancement. In addition, we found no evidence for any purely monocular
      influences on global motion detection. The results suggest that the site of
      binocular combination for global motion perception occurs prior to the extra
      striate cortex where motion integration occurs. All cells involved are binocular
      and exhibit dichoptic interactions, suggesting the existence of a neural
      mechanism that involves more than just simple summation of the two monocular
      inputs.

PMID- 17442360
TI  - Hydrolysis of pyrethroids by human and rat tissues: examination of intestinal,
      liver and serum carboxylesterases.
AB  - Hydrolytic metabolism of pyrethroid insecticides in humans is one of the major
      catabolic pathways that clear these compounds from the body. Rodent models are
      often used to determine the disposition and clearance rates of these esterified
      compounds. In this study the distribution and activities of esterases that
      catalyze pyrethroid metabolism have been investigated in vitro using several
      human and rat tissues, including small intestine, liver and serum. The major
      esterase in human intestine is carboxylesterase 2 (hCE2). We found that the
      pyrethroid trans-permethrin is effectively hydrolyzed by a sample of pooled human
      intestinal microsomes (5 individuals), while deltamethrin and bioresmethrin are
      not. This result correlates well with the substrate specificity of recombinant
      hCE2 enzyme. In contrast, a sample of pooled rat intestinal microsomes (5
      animals) hydrolyze trans-permethrin 4.5-fold slower than the sample of human
      intestinal microsomes. Furthermore, it is demonstrated that pooled samples of
      cytosol from human or rat liver are approximately 2-fold less hydrolytically
      active (normalized per mg protein) than the corresponding microsomal fraction
      toward pyrethroid substrates; however, the cytosolic fractions do have
      significant amounts (approximately 40%) of the total esteratic activity.
      Moreover, a 6-fold interindividual variation in carboxylesterase 1 protein
      expression in human hepatic cytosols was observed. Human serum was shown to lack
      pyrethroid hydrolytic activity, but rat serum has hydrolytic activity that is
      attributed to a single CE isozyme. We purified the serum CE enzyme to homogeneity
      to determine its contribution to pyrethroid metabolism in the rat. Both trans
      permethrin and bioresmethrin were effectively cleaved by this serum CE, but
      deltamethrin, esfenvalerate, alpha-cypermethrin and cis-permethrin were slowly
      hydrolyzed. Lastly, two model lipase enzymes were examined for their ability to
      hydrolyze pyrethroids. However, no hydrolysis products could be detected.
      Together, these results demonstrate that extrahepatic esterolytic metabolism of
      specific pyrethroids may be significant. Moreover, hepatic cytosolic and
      microsomal hydrolytic metabolism should each be considered during the development
      of pharmacokinetic models that predict the disposition of pyrethroids and other
      esterified compounds.

PMID- 17442361
TI  - Activation/proliferation and apoptosis of bystander goat lymphocytes induced by a
      macrophage-tropic chimeric caprine arthritis encephalitis virus expressing SIV
      Nef.
AB  - Caprine arthritis encephalitis virus (CAEV) is the natural lentivirus of goats,
      well known for its tropism for macrophages and its inability to cause infection
      in lymphocytes. The viral genome lacks nef, tat, vpu and vpx coding sequences. To
      test the hypothesis that when nef is expressed by the viral genome, the virus
      became toxic for lymphocytes during replication in macrophages, we inserted the
      SIVsmm PBj14 nef coding sequences into the genome of CAEV thereby generating CAEV
      nef. This recombinant virus is not infectious for lymphocytes but is fully
      replication competent in goat macrophages in which it constitutively expresses
      the SIV Nef. We found that goat lymphocytes cocultured with CAEV-nef-infected
      macrophages became activated, showing increased expression of the interleukin-2
      receptor (IL-2R). Activation correlated with increased proliferation of the
      cells. Interestingly, a dual effect in terms of apoptosis regulation was observed
      in exposed goat lymphocytes. Nef was found first to induce a protection of
      lymphocytes from apoptosis during the first few days following exposure to
      infected macrophages, but later it induced increased apoptosis in the activated
      lymphocytes. This new recombinant virus provides a model to study the functions
      of Nef in the context of infection of macrophages, but in absence of infection of
      T lymphocytes and brings new insights into the biological effects of Nef on
      lymphocytes.

PMID- 17442363
TI  - The effect of dioptric blur on reading performance.
AB  - Little is known about the systematic impact of blur on reading performance. The
      purpose of this study was to quantify the effect of dioptric blur on reading
      performance in a group of normally sighted young adults. We measured monocular
      reading performance and visual acuity for 19 observers with normal vision, for
      five levels of optical blur (no-blur, 0.5, 1, 2, and 3D). Dioptric blur was
      induced using convex trial lenses placed in front of the testing eye, with the
      pupil dilated and in the presence of a 3mm artificial pupil. Reading performance
      was assessed using eight versions of the MNREAD Acuity Chart. For each level of
      dioptric blur, observers read aloud sentences on one of these charts, from large
      to small print. Reading time for each sentence and the number of errors made were
      recorded and converted to reading speed in words per minute. Visual acuity was
      measured using 4-orientation Landolt C stimuli. For all levels of dioptric blur,
      reading speed increased with print size up to a certain print size and then
      remained constant at the maximum reading speed. By fitting nonlinear mixed
      effects models, we found that the maximum reading speed was minimally affected by
      blur up to 2D, but was approximately 23% slower for 3D of blur. When the amount
      of blur increased from 0 (no-blur) to 3D, the threshold print size (print size
      corresponded to 80% of the maximum reading speed) increased from 0.01 to 0.88
      logMAR, reading acuity worsened from -0.16 to 0.58 logMAR, and visual acuity
      worsened from -0.19 to 0.64 logMAR. The similar rates of change with blur for
      threshold print size, reading acuity and visual acuity implicates that visual
      acuity is a good predictor of threshold print size and reading acuity. Like
      visual acuity, reading performance is susceptible to the degrading effect of
      optical blur. For increasing amount of blur, larger print sizes are required to
      attain the maximum reading speed.

PMID- 17442364
TI  - Object-based anisotropic mislocalization by retinotopic motion signals.
AB  - The relative visual positions of briefly flashed stimuli are systematically
      modified in the presence of motion signals. We have recently shown that the
      perceived position of a spatially extended flash stimulus is anisotropically
      shifted toward a single convergent point back along the trajectory of a moving
      object without a significant change in the perceived shape of the flash
      [Watanabe, K., & Yokoi, K. (2006). Object-based anisotropies in the flash-lag
      effect. Psychological Science, 17, 728-735]. In the previous experiment, the
      moving stimulus moved in both retinotopic and environmental coordinates. In the
      present study, we examined whether the anisotropic mislocalization depends on
      retinotopic or object motion signals. When the retinal image of a moving stimulus
      was rendered stationary by smooth pursuit, the anisotropic pattern of
      mislocalization was not observed. In contrast, when the retinal image of a
      stationary stimulus was moved by eye movements, anisotropic mislocalization was
      observed, with the magnitude of the mislocalization comparable to that in the
      previous study. In both cases, there was little indication of shape distortion of
      the flash stimulus. These results demonstrate a clear case of object-based
      mislocalization by retinotopic motion signals; retinotopic--not object--motion
      signals distort the perceived positions of visual objects after the shape
      representations are established.

PMID- 17442365
TI  - A comparison of refractive development between two subspecies of infant rhesus
      monkeys (Macaca mulatta).
AB  - PURPOSE: Different subspecies of rhesus monkeys (Macaca mulatta) that are derived
      from different geographical locations, primarily Indian and China, are commonly
      employed in vision research. Substantial morphological and behavioral differences
      have been reported between Chinese- and Indian-derived subspecies. The purpose of
      this study was to compare refractive development in Chinese- and Indian-derived
      rhesus monkeys. METHODS: The subjects were 216 Indian-derived and 78 Chinese
      derived normal infant rhesus monkeys. Cross-sectional data were obtained at 3
      weeks of age for all subjects. In addition, longitudinal data were obtained from
      10 Indian-derived (male=5, female=5) and 5 Chinese-derived monkeys (male=3,
      female=2) that were reared with unrestricted vision. Ocular and refractive
      development was assessed by retinoscopy, keratometry, video-based
      ophthalmophakometry, and A-scan ultrasonography. RESULTS: Although the course of
      emmetropization was very similar in these two groups of rhesus monkeys, there
      were consistent and significant inter-group differences in ocular dimensions and
      refractive error. Throughout the observation period, the Chinese-derived monkeys
      were on average about 0.4D less hyperopic than the Indian-derived monkeys and the
      Chinese-derived monkeys had longer overall axial lengths, deeper anterior and
      vitreous chamber depths, thicker crystalline lenses, flatter corneas and lower
      powered crystalline lenses. CONCLUSIONS: The ocular differences observed in this
      study presumably reflect genetic differences between subspecies but could reflect
      the differences in the genetic pool between isolated colonies rather than true
      subspecies differences. Nonetheless, the substantial ocular differences that we
      observed emphasize that caution must be exercised when comparing and/or pooling
      data from rhesus monkeys obtained from different colonies. These inter-subspecies
      differences might be analogous to the ethnic differences in ocular parameters
      that have been observed in humans.

PMID- 17442367
TI  - Blurred edges look faint, and faint edges look sharp: the effect of a gradient
      threshold in a multi-scale edge coding model.
AB  - A multi-scale model of edge coding based on normalized Gaussian derivative
      filters successfully predicts perceived scale (blur) for a wide variety of edge
      profiles [Georgeson, M. A., May, K. A., Freeman, T. C. A., & Hesse, G. S. (in
      press). From filters to features: Scale-space analysis of edge and blur coding in
      human vision. Journal of Vision]. Our model spatially differentiates the
      luminance profile, half-wave rectifies the 1st derivative, and then
      differentiates twice more, to give the 3rd derivative of all regions with a
      positive gradient. This process is implemented by a set of Gaussian derivative
      filters with a range of scales. Peaks in the inverted normalized 3rd derivative
      across space and scale indicate the positions and scales of the edges. The edge
      contrast can be estimated from the height of the peak. The model provides a
      veridical estimate of the scale and contrast of edges that have a Gaussian
      integral profile. Therefore, since scale and contrast are independent stimulus
      parameters, the model predicts that the perceived value of either of these
      parameters should be unaffected by changes in the other. This prediction was
      found to be incorrect: reducing the contrast of an edge made it look sharper, and
      increasing its scale led to a decrease in the perceived contrast. Our model can
      account for these effects when the simple half-wave rectifier after the 1st
      derivative is replaced by a smoothed threshold function described by two
      parameters. For each subject, one pair of parameters provided a satisfactory fit
      to the data from all the experiments presented here and in the accompanying paper
      [May, K. A. & Georgeson, M. A. (2007). Added luminance ramp alters perceived edge
      blur and contrast: A critical test for derivative-based models of edge coding.
      Vision Research, 47, 1721-1731]. Thus, when we allow for the visual system's
      insensitivity to very shallow luminance gradients, our multi-scale model can be
      extended to edge coding over a wide range of contrasts and blurs.

PMID- 17442366
TI  - Image segregation in strabismic amblyopia.
AB  - Humans with naturally occurring amblyopia show deficits thought to involve
      mechanisms downstream of V1. These include excessive crowding, abnormal global
      image processing, spatial sampling and symmetry detection and undercounting.
      Several recent studies suggest that humans with naturally occurring amblyopia
      show deficits in global image segregation. The current experiments were designed
      to study figure-ground segregation in amblyopic observers with documented
      deficits in crowding, symmetry detection, spatial sampling and counting, using
      similar stimuli. Observers had to discriminate the orientation of a figure (an
      "E"-like pattern made up of 17 horizontal Gabor patches), embedded in a 7x7 array
      of Gabor patches. When the 32 "background" patches are vertical, the "E" pops
      out, due to segregation by orientation and performance is perfect; however, if
      the background patches are all, or mostly horizontal, the "E" is camouflaged, and
      performance is random. Using a method of constant stimuli, we varied the number
      of "background" patches that were vertical and measured the probability of
      correct discrimination of the global orientation of the E (up/down/left/right).
      Surprisingly, amblyopes who showed strong crowding and deficits in symmetry
      detection and counting, perform normally or very nearly so in this segregation
      task. I therefore conclude that these deficits are not a consequence of abnormal
      segregation of figure from background.

PMID- 17442368
TI  - Control charts for the toxicity of finished water--modeling the structure of
      toxicity.
AB  - The aim of this study was to construct control charts for the data that were
      obtained from the daily toxicological analysis of finished water (that is the
      water which has already been treated for human consumption) from the treated
      water tanks of the Water Supply & Sewerage Corporation of Athens. The basic idea
      of the control charts is to test the hypothesis that there are only common causes
      of variability versus the alternative that there are special causes. The control
      charts are designed and evaluated under the assumption that the observations from
      the process are independent and identically distributed (iid) normally. However,
      the independence assumption is often violated in practice. Time or serial
      dependence (autocorrelation) may be present in many chemical procedures, and may
      have a significant effect on the properties of the control charts. The fact that
      a serious amount of autocorrelation was present in the data for the toxicity of
      the fished water had a serious impact on the typical control charts. The problem
      of the autocorrelation was overcome by the usage of a more sophisticated method
      based on time-series ARIMA models.

PMID- 17442369
TI  - Understanding soluble microbial products (SMP) as a component of effluent organic
      matter (EfOM).
AB  - Formation of soluble microbial products (SMP) during biological degradation of
      organic compounds in a sequencing batch reactor (SBR) was investigated using high
      performance liquid chromatography--size exclusion chromatography (HPSEC) as well
      as other organic matter characterization tools. Results showed that carbon
      compounds in a glucose feed solution were totally transformed to other organic
      products classified biomass-associated products (BAP). The SMP-BAP contained in
      the SBR effluent consisted mainly of high-molecular weight (MW) fractions of
      organic matter, possibly originating from cell lysis. These compounds exhibited a
      low specific ultraviolet absorbance (SUVA) and a hydrophilic character. In
      addition, the characteristics of bulk effluent organic matters (EfOM) samples
      from wastewater treatment facilities were studied. It was observed that EfOM
      consisted of humic-like and hydrophobic (HPO) compounds, derived from the
      corresponding drinking water source, in addition to SMP-BAP. A superimposition of
      SEC chromatograms of the SMP-BAP and humic-like compounds represented a
      fingerprint of EfOM.

PMID- 17442370
TI  - Detection and remediation of human-origin pollution at two public beaches in
      Virginia using multiple source tracking methods.
AB  - Two public beaches (Anderson and Hilton) in Newport News, Virginia, were
      frequently closed to swimming in 2004 due to high Enterococcus spp. counts that
      exceeded the regulatory standard. The microbial source tracking (MST) methods of
      antibiotic resistance analysis (ARA) and fluorometry (to detect optical
      brighteners) were used in the summer of 2004 to determine the origins of fecal
      pollution at the two beaches. Both MST methods detected substantial human-origin
      pollution at the two beaches, in locations producing consistently high levels of
      Enterococcus spp. Investigations by municipal officials led to the fluorometric
      detection and subsequent repair of sewage infrastructure problems at both
      beaches. The success of the mitigation efforts was confirmed during the summer of
      2005 using ARA and fluorometry, with the results cross-validated by pulsed-field
      gel electrophoresis (PFGE).

PMID- 17442371
TI  - Differential expression of alpha-methylacyl-coenzyme A racemase in colorectal
      carcinoma bears clinical and pathologic significance.
AB  - alpha-methylacyl-coenzyme A racemase (AMACR) is a recently discovered biomarker
      that is shown to be overexpressed in some prostatic carcinomas and associated
      with prostatic cancer progression. Given that AMACR plays an important role in
      peroxisomal beta-oxidation of branched-chain fatty acids from red meat and dairy
      products, and that consumption of red meat may increase risk of developing colon
      cancer as suggested by epidemiological studies, it is plausible to explore the
      function of AMACR in colorectal carcinoma. A few previous studies have indeed
      observed overexpression of AMACR in 45% to 69% of the colorectal carcinomas.
      However, the clinical and pathologic characteristics of such AMACR expressers
      have not been investigated. In this study, the immunohistochemical expression
      pattern of AMACR of 163 patients with primary colorectal carcinoma treated
      primarily with surgical resection was analyzed and correlated with tumor
      pathologic features (tumor location, histologic type, grade, pathologic stage,
      lymph node and distant metastasis) and patient outcome (disease-specific
      survival). The results showed variable positive staining for AMACR in 123 (75%)
      of 163 tumors, and moderate to strong staining in 63 (39%) of 163. Lack of
      staining or low-intensity staining appeared to correlate significantly with
      mucinous histology (P < .001), poor tumor differentiation (P = .021), and
      presence of lymphovascular invasion (P = .032). Patients whose tumors showed lack
      of staining or low-intensity staining also had a significantly worse 5-year
      disease-specific survival (P < .012), as did patients whose tumors had
      lymphovascular invasion, or were of high American Joint Committee on Cancer
      (AJCC) stage. On multivariate analysis, AMACR staining and AJCC staging remained
      independent predictors for patient outcome. Thus, our data suggest that AMACR
      expression in colorectal carcinoma correlates with certain tumor pathologic
      characteristics (histologic type, differentiation, and lymphovascular invasion)
      and patient outcome. Additional confirmatory studies are needed to establish the
      significance of AMACR as a prognostic marker for colorectal carcinoma. Further
      investigation on interaction between AMACR and other known colorectal cancer
      development pathways may provide new insights on colorectal carcinogenesis.

PMID- 17442372
TI  - Increased pontin expression in human colorectal cancer tissue.
AB  - Wnt signaling plays a fundamental role in the control of cell proliferation and
      differentiation and is frequently deregulated in colorectal carcinoma leading to
      an enhanced expression of Wnt target genes. Pontin, a member of the AAA(+)
      superfamily, has previously been shown to interact with beta-catenin and to
      enhance TCF/beta-catenin-mediated transcription of Wnt target genes and thus may
      contribute to carcinogenesis. Here, we studied the expression of pontin in 34
      patients with histologically proven colorectal cancer by immunohistochemistry on
      paraffin-embedded colorectal cancer samples using the monoclonal mouse anti
      pontin (5G3-11) antibody. Cytoplasmic pontin staining of tumor cells was present
      in all cases and was stronger in 84.6% and equal in 15.4% of the cases compared
      with normal mucosa. In 50% of tumor specimens, an additional nuclear pontin
      staining pattern was noted with positivity ranging from 10% to 60% of the nuclei.
      Interestingly, all cases with nuclear pontin expression also revealed nuclear
      beta-catenin localization. Furthermore, pontin staining was stronger at the
      invasive margin and in tumor buds than in the tumor center in 41.2% and 37.9% of
      the cases, respectively. In this context, 66.7% and 64.7% of the cases with
      enhanced beta-catenin staining at the invasive margin and in tumor buds,
      respectively, also revealed stronger pontin expression. Analysis of pontin
      expression in 8 patients by Western blotting confirmed the histologic results.
      These data suggest that upregulation and nuclear localization of pontin together
      with beta-catenin may contribute to progression of colorectal carcinoma.

PMID- 17442373
TI  - Insulinlike growth factor I receptor and estrogen receptor beta expressions are
      inversely correlated in colorectal neoplasms and affected by the insulin
      resistance syndrome.
AB  - The present study aimed at evaluating the modulation of insulin-like growth
      factor I receptor (IGF-IR) and estrogen receptor beta (ER-beta) expression and
      their correlation during tumorigenesis of sporadic colorectal cancer, with
      particular interest in the insulin resistance syndrome. In a series of 100
      individuals (54 men and 46 women; mean age, 67.3 +/- 9.4 years) with colorectal
      neoplasms, classified as early adenomas (n = 25), advanced adenomas (n = 44), and
      adenocarcinomas (n = 31), IGF-IR and ER-beta expression was quantified in
      formalin-fixed, paraffin-embedded biopsy specimens, using confocal laser scanning
      microscopy and a computer-based method for assessment of immunofluorescent
      staining. All individuals were evaluated for insulin resistance markers
      (hyperglycemia, dyslipidemia, central obesity, and arterial hypertension), and 50
      (26 men and 24 women; mean age, 68.2 +/- 9.0 years) were diagnosed with the
      insulin resistance syndrome. For the sequence of early adenoma-advanced adenoma
      adenocarcinoma, a gradual increase in IGF-IR expression and a gradual decrease in
      ER-beta expression were observed. The partial correlation coefficient between IGF
      IR and ER-beta expression, controlled for age, sex, insulin resistance, type of
      lesion, and location of lesion was 0.295 (P = .004, 2-tailed significance).
      Analysis of variance demonstrated that the effect of the insulin resistance
      syndrome on IGF-IR and ER-beta expression was significant (P = .007 and P = .018,
      respectively). The results suggest the combined effect of IGF-I and estrogens in
      colorectal cancer, with a distinctive role in individuals with the insulin
      resistance syndrome.

PMID- 17442374
TI  - Prognostic value of integrin beta1-ILK-pAkt signaling pathway in non-small cell
      lung cancer.
AB  - Cell adhesion signaling via the integrin-extracellular matrix connection plays a
      critical role in the growth and survival of normal adhering cells. Integrin
      linked kinase is a ubiquitously expressed serine-threonine protein kinase capable
      of interacting with the cytoplasmic domains of integrin beta1 and beta3 and plays
      a critical role of an interface between integrin and the cytoskeleton in integrin
      dependent cell adhesion, spreading, and cell shape change. In this study, we
      evaluated integrin beta1, integrin-linked kinase, and phosphorylated-Akt (Ser
      473; pAkt) expressions in 118 consecutive non-small cell lung cancer tissue
      samples surgically resected between 1997 and 2000. As a result, we identified the
      specific subset of strong membranous staining of integrin beta1, strong
      cytoplasmic staining of integrin-linked kinase, and strong cytoplasmic staining
      with a granular pattern of pAkt in the non-small cell lung cancer tissue samples.
      In addition, we provide evidence that integrin-linked kinase, integrin beta1, and
      the activated form of Akt are mutually associated with poor prognosis in non
      small cell lung cancer and that the simultaneous overexpression of these proteins
      is an independent prognostic factor (hazard ratio, 2.771; P = .003) comparable
      with standard prognostic factors such as T factor and lymphatic invasion by
      multivariate analysis. Thus, further studies of the integrin beta1-integrin
      linked kinase-pAkt signaling pathway may provide a novel prognostic marker and
      therapeutic target for non-small cell lung cancer.

PMID- 17442375
TI  - Consequences of p16 tumor suppressor gene inactivation in mycosis fungoides and
      Sezary syndrome and role of the bmi-1 and ras oncogenes in disease progression.
AB  - In examining the expression of oncogenes and tumor suppressor genes in mycosis
      fungoides and Sezary syndrome, we found the cell cycle-regulating protein p16 to
      be absent in T cells. Immunohistochemical staining with p16-specific antibodies
      showed that the number of p16-expressing cells in cutaneous lesions decreases in
      late stages. The repression of p16 was not attributable to deletion or
      methylation of this gene; however, the Bmi-1 oncogene, a known suppressor of p16,
      was present in mycosis fungoides and Sezary syndrome cell lines and skin lesions.
      The absence of p16 correlated with the phosphorylation of the retinoblastoma
      protein on cyclin D/CDK4- or cyclin D/CDK6-specific sites. Ki-ras, which
      stimulates phosphorylation of retinoblastoma via cyclin-dependent kinases, was
      found in all tested cutaneous T-cell lymphoma samples; and its expression
      generally was stronger in advanced stages. Thus, cutaneous T-cell lymphoma cells
      show changes in oncogene and tumor suppressor gene expression that increase
      proliferation.

PMID- 17442376
TI  - Immunohistochemical detection of hepatocyte nuclear factor 1beta in ovarian and
      endometrial clear-cell adenocarcinomas and nonneoplastic endometrium.
AB  - Recent studies have noted specific expression of hepatocyte nuclear factor (HNF)
      1beta in ovarian clear-cell adenocarcinoma (CCA). In this study, we aimed to
      determine whether HNF-1beta can be a specific marker of CCA in both the ovary and
      the endometrium and to assess the pathological significance of HNF-1beta
      expression in CCAs. We examined HNF-1beta expression immunohistochemically in 186
      ovarian carcinomas, including 40 CCAs; 33 endometrial carcinomas, including 5
      CCAs; 22 endometria at different stages of the menstrual cycle (5 in the
      proliferative, 12 in the secretory, and 5 in the menstrual phases); and 7
      gestational endometria. The incidence of HNF-1beta immunoreactivity differed
      significantly between CCAs and other histology in both the ovary (100% in the
      former versus 2% in the latter) and the endometrium (100% in the former versus 0%
      in the latter) (P < .0001 each). In nonneoplastic endometrium, 25% or more
      immunoreactive cells were confined to the mid-to-late secretory phase of the
      menstrual cycle and gestational endometrium. HNF-1beta would be an excellent
      marker for distinguishing CCAs from other lesions in both the ovary and the
      endometrium. HNF-1beta expression seems to be associated with physiopathological
      cytoplasmic glycogen accumulation in these organs.

PMID- 17442377
TI  - Clinicopathological significance of missing in metastasis B expression in
      hepatocellular carcinoma.
AB  - Missing in metastasis (MIM) proteins are important regulators in controlling cell
      growth and development. There has been accumulating evidence suggesting a role of
      MIM-B in carcinogenesis, yet its role in the development of hepatocellular
      carcinoma has not been examined thus far. In this study, we investigated the
      clinicopathological significance of MIM-B in tumor and its matched adjacent
      nontumor tissue obtained from 40 patients with hepatocellular carcinoma.
      Increased MIM-B messenger RNA and protein expression, as detected by quantitative
      real-time polymerase chain reaction and Western blot, respectively, was found in
      hepatocellular carcinoma clinical samples; and its expression was significantly
      associated with early pathologic tumor-node-metastasis stage group (P = .007),
      presence of tumor encapsulation (P = .034), and absence of venous infiltration (P
      = .038). Higher levels of MIM-B expression were found to be associated with early
      stage disease. Elevated MIM-B expression may influence the development of
      hepatocellular carcinoma and may possibly be a powerful indicator for the disease
      at an early stage.

PMID- 17442378
TI  - Leprosy-specific B-cells within cellular infiltrates in active leprosy lesions.
AB  - Leprosy is a spectral disease with polar lepromatous and tuberculoid forms
      correlating with enhanced humoral and cell-mediated immunity, respectively,
      against Mycobacterium leprae and the borderline forms, borderline lepromatous,
      midborderline, and borderline tuberculoid showing in-between clinical and
      immunological characteristics. Histopathologically, the cellular infiltrates of
      leprosy lesions show predominantly the presence of interacting T-cells and
      antigen presenting cells like macrophages, whereas the presence of B-cells has
      only been sporadically reported. The present study demonstrates by
      immunohistochemical techniques the presence of B-cells, including plasma cells,
      in active lesions from lepromatous leprosy, skin smear negative borderline
      lepromatous, and paucibacillary borderline tuberculoid leprosy. Furthermore, the
      study demonstrates the in situ production of M leprae-specific antibodies from BT
      lesions using an organotypic skin explant culture model. Finally, analysis of the
      cytokine release profile in supernatants of lesional organotypic skin cultures
      showed a microenvironment conducive to the differentiation and maturation of B
      cells. The results demonstrate the presence of different functionally active B
      cell stages within lesions of patients with leprosy, including borderline
      tuberculoid patients, which could secrete anti-M leprae-specific antibodies.
      However, their role in leprosy pathology remains to be elucidated.

PMID- 17442379
TI  - Increased angiogenesis in chronic idiopathic myelofibrosis: vascular endothelial
      growth factor as a prominent angiogenic factor.
AB  - Increased angiogenesis has been suggested to be implicated in the pathogenesis of
      chronic idiopathic myelofibrosis (CIMF). We hypothesized that vascular
      endothelial growth factor (VEGF) drives CIMF-associated angiogenesis, and thus,
      we aimed to determine its expression and biologic impact in newly diagnosed
      patients. All patients with CIMF diagnosed between 1990 and 2001, for whom
      adequate bone marrow specimens and clinical data were available, were deemed
      eligible. Each case was reclassified according to World Health Organization
      criteria. Microvessel density (MVD), as assessed by CD34 staining, and VEGF
      expression were examined by standard immunohistochemistry on paraffin-embedded
      trephine bone marrow biopsy specimens. The cytogenetic phenotype was determined
      by fluorescence in situ hybridization. Appropriate summary statistics were used
      for comparisons between groups; survival was calculated using Kaplan-Meier
      estimates. Parameters found to be of prognostic significance in univariate
      analysis were verified in a multivariate Cox regression model. Fifty-five
      patients with CIMF were investigated. With a median of 43 vascular lumina per
      0.747 mm(2), patients with CIMF displayed significantly greater MVD than did age
      matched controls (n = 10; median MVD, 19; P < .001) with equal distribution
      between the various fibrosis stages. Moreover, VEGF expression was significantly
      increased in CIMF (median, 12 cells/0.747 mm(2) versus 1.4 cells/0.747 mm(2); P =
      .01) and correlated with MVD (P = .001). However, neither MVD nor VEGF expression
      correlated with cytogenetics or clinical outcome. We conclude that in CIMF,
      increased MVD is detectable even in early (pre-)fibrotic stages. Moreover, we
      found significantly elevated VEGF expression correlating with MVD, thus
      suggesting VEGF to play a prominent angiogenic role and representing a novel
      potential therapeutic target in CIMF.

PMID- 17442380
TI  - Temporal moisture content variability beneath and external to a building and the
      potential effects on vapor intrusion risk assessment.
AB  - Migration of vapors from organic chemicals residing in the subsurface into
      overlying buildings is known as vapor intrusion. Because of the difficulty in
      evaluating vapor intrusion by indoor air sampling, models are often employed to
      determine if a potential indoor inhalation exposure pathway exists and, if such a
      pathway is complete, whether long-term exposure increases the occupants' risk for
      cancer or other toxic effects to an unacceptable level. For site-specific vapor
      intrusion assessments, moisture content is, at times, determined from soil cores
      taken in open spaces between buildings. However, there is little published
      information on how moisture content measured outside a building structure
      compares with the moisture content directly beneath the building - where the
      values are most critical for vapor intrusion assessments. This research begins to
      address these issues by investigating the movement of soil moisture next to and
      beneath a building at a contaminated field site and determining the effect on
      vapor intrusion risk assessment. A two-dimensional, variably-saturated water flow
      model, HYDRUS-2D, is used with 2 years of hourly, local rainfall data to simulate
      subsurface moisture content in the vicinity of a hypothetical 10 x 10-m building
      slab at a contaminated field site. These moisture content values are used in
      vapor intrusion risk assessment simulations using the Johnson and Ettinger model
      with instantaneous and averaged moisture contents. Results show that vapor
      intrusion risk assessments based on moisture content determined from soil cores
      taken external to a building structure may moderately-to-severely underestimate
      the vapor intrusion risk from beneath the structure. Soil under the edges of a
      slab may be influenced by rainfall events and may show reduced vapor intrusion
      risk as a consequence. Data from a building instrumented with subslab moisture
      probes showed results similar to the modeling, but with a smaller difference
      between the subslab and outside average moisture contents. These results indicate
      that, depending upon the point of vapor ingress into the structure and soil type,
      risk-based cleanup concentrations based on outside-of-slab or default moisture
      content values may not be predictive of exposure to organic vapors from below a
      building.

PMID- 17442381
TI  - Biochemistry meets nuclear architecture: multicolor immuno-FISH for co
      localization analysis of chromosome segments and differentially expressed gene
      loci with various histone methylations.

PMID- 17442382
TI  - Detection of micrometastases in the sentinel lymph nodes of patients with
      endometrial cancer.
AB  - OBJECTIVE: We investigated the utility of sentinel lymph node (SLN) mapping for
      the detection of endometrial carcinoma micrometastases. We reevaluated the
      accuracy of our SLN detection procedure, this time combining step-serial section
      with cytokeratin immunostaining. PATIENTS AND METHODS: Between March 2002 and
      March 2005, consecutive patients undergoing laparotomy (total abdominal
      hysterectomy, bilateral salpingo-oophorectomy, total pelvic lymphadenectomy and
      para-aortic lymphadenectomy to the level of renal veins) with SLN biopsy for
      endometrial cancer at Tohoku University Hospital were enrolled in this study.
      Excluded were patients in whom lymph node metastases were detected by routine
      histological examination or those without detectable SLNs. All surgically removed
      lymph nodes, including SLNs, were examined histopathologically by
      immunohistochemistry staining with an anti-cytokeratin antibody (AE1/AE3)
      combined with step-serial sectioning at 200-500 microm intervals. RESULTS: Four
      of seventy-four SLNs (5%) obtained from 20 patients had micrometastases or
      isolated tumor cells (ITC). In contrast, only 4 of the 1350 non-SLNs obtained
      from 20 patients (0.3%) had detectable micrometastases. The micrometastases were
      detected in the external iliac basin (two cases) and in the para-aortic area (two
      cases). The isolated tumor cell was detected in the external iliac basin (one
      case). CONCLUSION: SLNs detected by our method had micrometastases more
      frequently than did non-SLNs. Easy detection of micrometastases by immunostaining
      is only possible with step-serial sectioning of the SLNs.

PMID- 17442383
TI  - Intraoperative lymphatic mapping and sentinel node biopsy using hysteroscopy in
      patients with endometrial cancer.
AB  - OBJECTIVE: The purpose of the study was to assess the feasibility of
      intraoperative sentinel node (SN) detection using injection of patent blue dye
      and radioactive tracer beneath the tumor of patients with endometrial carcinoma.
      METHODS: Hysteroscopy was used for injection of 2 ml of patent-V blue, followed
      by 20-50 MBq technetium-99 m-labelled nanocolloids into the subendometrial layer
      underlying the tumor of 60 patients with endometrial cancer. Then SN biopsy,
      pelvic and paraaortic lymphadenectomy, hysterectomy and bilateral salpingo
      oophorectomy were carried out through laparotomy or laparoscopy. RESULTS: Sixty
      patients aged 43 years to 87 years (median age 65 years) were enrolled in this
      study. Sentinel nodes were identified in 49 of 60 patients (82%). The mean number
      of SN retrieved was 3.7 per patient (range, 1 to 8). Sixteen patients (33%) had
      SN in both pelvic and paraaortic areas. No patient had SN only at the paraaortic
      level. Metastatic disease was found in 9 patients (15%). In 8 of them at least
      one SN was positive. CONCLUSION: Intraoperative sentinel node detection is
      feasible in patients with endometrial carcinoma using hysteroscopy for injection
      of blue dye and technetium-99 m beneath the tumor. This technique may actually
      enhance the chances of detecting metastatic disease, while reducing the extent of
      the surgery.

PMID- 17442384
TI  - Molecular architecture and functional model of the complete yeast ESCRT-I
      heterotetramer.
AB  - The endosomal sorting complex required for transport-I (ESCRT-I) complex, which
      is conserved from yeast to humans, directs the lysosomal degradation of
      ubiquitinated transmembrane proteins and the budding of the HIV virus. Yeast
      ESCRT-I contains four subunits, Vps23, Vps28, Vps37, and Mvb12. The crystal
      structure of the heterotetrameric ESCRT-I complex reveals a highly asymmetric
      complex of 1:1:1:1 subunit stoichiometry. The core complex is nearly 18 nm long
      and consists of a headpiece attached to a 13 nm stalk. The stalk is important for
      cargo sorting by ESCRT-I and is proposed to serve as a spacer regulating the
      correct disposition of cargo and other ESCRT components. Hydrodynamic constraints
      and crystallographic structures were used to generate a model of intact ESCRT-I
      in solution. The results show how ESCRT-I uses a combination of a rigid stalk and
      flexible tethers to interact with lipids, cargo, and other ESCRT complexes over a
      span of approximately 25 nm.

PMID- 17442385
TI  - Seasonality affects post-thaw plasma membrane intactness and sperm velocities in
      spermatozoa from Thai AI swamp buffaloes (Bubalus bubalis).
AB  - Altogether 218 frozen semen AI doses, prepared between 1980 and 1989 and also
      between 2003 and 2005 from 18 AI Thai swamp buffalo sires, were examined to
      determine whether seasonality affects post-thaw viability, as plasma membrane
      integrity (PMI, using SYBR-14/PI), plasma membrane stability (PMS, using Annexin
      V/PI), or motility (Mot, using CASA). A thermoresistance test (38 degrees C for
      60 min) was used to further analyze sperm survivability in vitro. All variables
      were compared over 3 seasons of the year (rainy: July-October; winter: November
      February; and summer: March-June), with distinct ambient temperature and
      humidity. PMI (% of alive spermatozoa) was higher in winter (54.6%, P<0.001) than
      in the rainy (43.5%) or summer (46.7%) seasons. Outcomes of PMS (Annexin-V/PI
      assay) confirmed those of PMI, the highest PMS in spermatozoa processed in winter
      (55.7%, P<0.001). Spermatozoa depicting linear Mot post-thaw ranged from 48.2% to
      48.8% across seasons (ns), proportions that decreased during incubation (33.5
      37.9%), albeit without seasonal differences. The mean percentages of straight
      linear velocity (VSL), average path velocity (VAP), or curvilinear velocity (VCL)
      were higher (P<0.05-0.001) in the rainy season than in winter or summer, while
      average lateral head displacement (ALH) was higher (P<0.05) in summer,
      differences maintained after incubation. In conclusion, post-thaw PMS and PMI,
      assessed by flow cytometry, were significantly better in sperm samples processed
      during winter than in samples processed during the other seasons of the year, a
      seasonal difference not picked up by CASA, probably due to the larger number of
      spermatozoa assessed.

PMID- 17442386
TI  - Dental adhesion review: aging and stability of the bonded interface.
AB  - OBJECTIVE: Most of current dental adhesive systems show favorable immediate
      results in terms of retention and sealing of bonded interface, thereby
      counteracting polymerization shrinkage that affects resin-based restorative
      materials. Despite immediate efficacy, there are major concerns when dentin
      bonded interfaces are tested after aging even for short time period, i.e. 6
      months. METHODS: This study critically discusses the latest peer-reviewed reports
      related to formation, aging and stability of resin bonding, focusing on the micro
      and nano-phenomena related to adhesive interface degradation. RESULTS: Most
      simplified one-step adhesives were shown to be the least durable, while three
      step etch-and-rinse and two-step self-etch adhesives continue to show the highest
      performances, as reported in the overwhelming majority of studies. In other
      words, a simplification of clinical application procedures is done to the
      detriment of bonding efficacy. Among the different aging phenomena occurring at
      the dentin bonded interfaces, some are considered pivotal in degrading the hybrid
      layer, particularly if simplified adhesives are used. Insufficient resin
      impregnation of dentin, high permeability of the bonded interface, sub-optimal
      polymerization, phase separation and activation of endogenous collagenolytic
      enzymes are some of the recently reported factors that reduce the longevity of
      the bonded interface. SIGNIFICANCE: In order to overcome these problems, recent
      studies indicated that (1) resin impregnation techniques should be improved,
      particularly for two-step etch-and-rinse adhesives; (2) the use of conventional
      multi-step adhesives is recommended, since they involve the use of a hydrophobic
      coating of nonsolvated resin; (3) extended curing time should be considered to
      reduce permeability and allow a better polymerization of the adhesive film; (4)
      proteases inhibitors as additional primer should be used to increase the
      stability of the collagens fibrils within the hybrid layer inhibiting the
      intrinsic collagenolytic activity of human dentin.

PMID- 17442387
TI  - In vitro apatite formation on chemically treated (P/M) Ti-13Nb-13Zr.
AB  - OBJECTIVES: Titanium alloys are considered the material of choice when used as
      endosteal part of implants. However, they are not able to bond directly to bone.
      The objective of this study was to suggest a chemical surface treatment for Ti
      13Nb-13Zr to initiate the formation of hydroxy carbonated apatite (HCA) during in
      vitro bioactivity tests in simulated body fluid (SBF). METHODS: Titanium,
      niobium, and zirconium hydride powders were blended, compacted and sintered.
      Sintered Ti-13Nb-13Zr samples were etched in HCl, H(3)PO(4), and in a mixture of
      HF+HNO(3), respectively, and subsequently pretreated in NaOH. The influence of
      acid etching conditions on the microstructure of the Ti-13Nb-13Zr alloys as well
      as on the rate of HCA formation was evaluated using SEM-EDS, FTIR, and
      gravimetric analyses. RESULTS: Sintered Ti-13Nb-13Zr alloys consist of a
      Widmannstatten (alpha+beta) microstructure. Exposure of chemically etched and
      NaOH activated samples to SBF for 1 week leads to the formation of a HCA layer on
      the surface of HCl as well as H(3)PO(4) treated samples. No HCA formation was
      found on HNO(3) treated samples. After 2 weeks in SBF the mass increase, that can
      be correlated to the HCA formation rate, was the highest for HCl pretreated
      samples (2.4 mg/cm(2)) followed by H(3)PO(4) (0.8 mg/cm(2)) and HNO(3) pretreated
      ones (0.2 mg/cm(2)). SIGNIFICANCE: Since the in vitro HCA formation from SBF is
      generally accepted as a typical feature for bioactive materials, it is supposed
      that HCl etching with subsequent NaOH treatment might enhance the in vivo bone
      bonding ability of Ti-13Nb-13Zr.

PMID- 17442388
TI  - Development of in vitro tooth staining model and usage of catalysts to elevate
      the effectiveness of tooth bleaching.
AB  - OBJECTIVES: Whole blood or tea was frequently used to stain the teeth for
      measuring the effectiveness of different bleaching materials. However, the
      components of blood or tea cannot be quantitatively determined and variability
      might exist among different brands of tea. The purpose of this study was to
      develop a reproducible in vitro tooth-staining model to simulate the intrinsic
      discoloration of teeth and evaluate the ability of two catalysts to enhance the
      bleaching activity of H(2)O(2). METHODS: Rhodamine B, Orange II, Fe(III)
      phthalocyanine, and tea were used to stain the tooth specimens for 4-72 h and
      subsequently bleached by H(2)O(2) for 4-72 h. The process was photographed using
      a digital stereoscopic microscope and a digital camera. The image was transformed
      to get L*, a*, b* values of CIE Lab system with image processing software. The
      catalytic ability of light irradiation plus addition of Fe/Sodium-Y or Mn/Sodium
      Y for specimens stained by Orange II was evaluated in test tubes and in extracted
      tooth model. RESULTS: The color of specimens stained by Rhodamine B could not be
      sufficiently recovered after bleaching by H(2)O(2). In addition, the reaction of
      Fe(III) phthalocyanine with H(2)O(2) in test tubes was too fast to be monitored.
      Light activation plus use of Fe/Sodium-Y or Mn/Sodium-Y could significantly
      accelerate the bleaching efficiency of H(2)O(2). SIGNIFICANCE: Orange II was the
      most appropriate dye for tooth staining among the dyes used in this study.
      Addition of Fe/Sodium-Y or Mn/Sodium-Y plus light irradiation could elevate the
      bleaching efficacy of H(2)O(2) for those specimens stained by Orange II.

PMID- 17442389
TI  - Brief report: impact of classroom presentations about health and help-seeking on
      rural Australian adolescents' intentions to consult health care professionals.

PMID- 17442390
TI  - Aspiration biopsy-nucleic acid diagnosis of thyroid malignant lymphoma by
      vectorette PCR: experience of eight cases.
AB  - The usefulness of a new method to detect B-cell monoclonality named VR, which is
      a combination of the digestion with restriction enzymes and vectorette PCR, in
      aspiration biopsy-nucleic acid diagnosis (ABND) of thyroid malignant lymphoma was
      investigated. ABND was performed in 12 patients in whom malignant lymphoma was
      suspected. Among the patients who underwent open surgery, monoclonality was
      detected in the aspirates in four (50%) of eight patients with malignant
      lymphoma, but was not detected in one patient with Hashimoto disease. ABND using
      VR is a useful adjunct of aspiration biopsy cytology in the diagnosis of thyroid
      malignant lymphoma.

PMID- 17442391
TI  - Predictors of depressive symptoms among foster caregivers.
AB  - OBJECTIVES: The main purposes of this study were to determine (1) the prevalence
      of depressive symptoms among foster caregivers, (2) the social-demographics, risk
      factors, and social support predicting depressive symptoms, and (3) whether
      social support buffered the effects of the risk factors in the Illinois Foster
      Caregivers Study. METHOD: Telephone interviews were used to collect data from a
      sample of 189 foster caregivers in the State of Illinois. Interviewers pretested
      the survey instrument, which included valid and reliable instruments on
      depressive symptoms and adult report of childhood maltreatment, an important risk
      factor for depression. Multivariate ordered logistic regression models were
      estimated. RESULTS: The foster caregivers exhibited few depressive symptoms, with
      only one respondent scoring in the clinical range. Contrary to past research on
      the general population, caregivers reporting higher income were at an increased
      risk of exhibiting depressive symptoms. The three risk factors-experiencing less
      than excellent or very good health, childhood maltreatment, and insufficient time
      to carry out responsibilities-were related to higher levels of depressive
      symptoms. Foster caregivers who perceived their support group as helpful had a
      decreased risk of reporting depressive symptoms. We found no evidence that social
      support buffered the effects of the risk factors. CONCLUSIONS: The results
      indicate that foster caregivers were adequately screened for depression, but
      suggest that assessing and providing assistance for health problems, trauma from
      childhood maltreatment, and insufficient time to meet responsibilities might
      decrease depressive symptoms. Facilitating and enhancing the helpfulness of
      foster caregiver support groups also might decrease development of depressive
      symptoms.

PMID- 17442392
TI  - Molecular cloning and identification of macrophage migration inhibitory factor
      (MIF) in teleost fish.
AB  - Macrophage migration inhibitory factor (MIF) is one of the first cytokines to be
      identified, which have been emerged to be an important mediator of the innate and
      adaptive immune system. Although MIF was well characterized in several mammal
      species, there was still little report in fish. In present study, we cloned the
      MIF gene from Tetraodon nigroviridis, and identified other six MIF genes from
      other teleost fishes, Fundulus heteroclitu, Oncorhynchus mykiss, Ictalurus
      punctatus, Danio rerio, Salmo salar and Haplochromis chilotes. The results showed
      that the fish MIF genes with the same organization as the mammalians consist of
      three exons and two introns. Tetraodon MIF gene located within a 1091bp genomic
      fragment of chromosome 1, transcribed into a 500bp mRNA including 14bp 5'
      untranslated region (UTR), 348bp ORF and 138bp 3'-UTR. Tetraodon MIF with 115aa
      has a calculated molecular mass of 12.5kDa and a theoretical pI of 6.81. The
      deduced amino-acid sequences of the teleost fish MIFs showed 64.1-73.5% sequence
      identity to mammalian MIFs, 61.5-70.1% to avian MIFs, 55.6-62.4% to amphibian
      MIFs, 74.4-97.4% among the teleost fishes. Phylogenetic analysis separates the
      teleost fish MIFs into an exclusive group. Genomic Southern blotting analyses
      suggest that Tetraodon has one copy of the MIF gene. RT-PCR and real-time PCR
      analyses reveal that Tetraodon MIF (TnMIF) mRNA was constitutively expressed in
      10 selected tissues and induced by lipopolysaccharide (LPS) strikingly in head
      kidney and spleen. The bioactivity of recombinant TnMIF was tested by macrophage
      migration inhibition (MMI) assay. The result of MMI assay showed that the
      recombinant TnMIF inhibited the macrophage cells migration at rate of 35%
      (P<0.04). These results indicated that MIFs in fish may be involved in immune
      responses.

PMID- 17442393
TI  - Studies of the neural mechanisms of deep brain stimulation in rodent models of
      Parkinson's disease.
AB  - Several rodent models of deep brain stimulation (DBS) have been developed in
      recent years. Electrophysiological and neurochemical studies have been performed
      to examine the mechanisms underlying the effects of DBS. In vitro studies have
      provided deep insights into the role of ion channels in response to brain
      stimulation. In vivo studies reveal neural responses in the context of intact
      neural circuits. Most importantly, recording of neural responses to behaviorally
      effective DBS in freely moving animals provides a direct means for examining how
      DBS modulates the basal ganglia thalamocortical circuits and thereby improves
      motor function. DBS can modulate firing rate, normalize irregular burst firing
      patterns and reduce low-frequency oscillations associated with the Parkinsonian
      state. Our current efforts are focused on elucidating the mechanisms by which DBS
      effects on neural circuitry improve motor performance. New behavioral models and
      improved recording techniques will aide researchers conducting future DBS studies
      in a variety of behavioral modalities and enable new treatment strategies to be
      explored, such as closed-loop stimulations based on real-time computation of
      ensemble neural activity.

PMID- 17442394
TI  - Identification and pattern of perfluorooctane sulfonate (PFOS) isomers in human
      serum and plasma.
AB  - Human serum and plasma from Sweden (n=17), the United Kingdom (the UK) (n=13) and
      Australia (n=40) were analyzed by high performance liquid chromatography coupled
      to mass spectrometry. The objective was to identify different perfluorooctane
      sulfonate (PFOS) isomers. Similar isomer patterns typical for the electrochemical
      fluorination (ECF) process were found for all samples. The linear PFOS (L-PFOS)
      was the major isomer found (58-70%) followed by the monosubstituted PFOS isomers
      1/6-CF(3)-PFOS (18-22%) and 3/4/5-CF(3)-PFOS (13-18%). Disubstituted isomers were
      also detected. The percentage of L-PFOS found in the serum and plasma samples was
      lower compared to a standard PFOS product (76-79%). The pattern of PFOS isomers
      in human serum and plasma may be suggestive concerning potential isomeric
      discrimination since PFOS is only produced by ECF. Possibilities for such isomer
      discrimination are discussed. Significant higher content of L-PFOS (68%) in
      Swedish samples compared to Australia and the UK (59%) was also found, which may
      suggest differences in exposure sources for humans.

PMID- 17442395
TI  - Methylmercury-induced changes in mitochondrial function in striatal synaptosomes
      are calcium-dependent and ROS-independent.
AB  - The brain is the main target organ for methylmercury (MeHg), a highly toxic
      compound that bioaccumulates in aquatic systems, leading to high exposure in
      humans who consume large amounts of fish. The mechanisms responsible for MeHg
      induced changes in neuronal function are, however, not yet fully understood. In
      the present study we investigated whether MeHg-induced elevations in reactive
      oxygen species (ROS) or intracellular calcium are responsible for altering
      mitochondrial metabolic function in rat striatal synaptosomes. MeHg decreased
      mitochondrial function (measured by the conversion of MTT to formazan) and
      increased ROS levels in striatal synaptosomes after 30 min exposure. Although co
      incubation with the antioxidant Trolox significantly reduced MeHg-induced ROS
      levels, it failed to restore mitochondrial function. MeHg also increased
      cytosolic and mitochondrial calcium levels in striatal synaptosomes. These
      elevations were largely independent of extrasynaptosomal calcium, given that
      nominal calcium-free buffer with 20 microM EGTA did not prevent MeHg-induced
      increases in cytosolic calcium. In conclusion, we suggest that ROS are not the
      cause of mitochondrial dysfunction in striatal synaptosomes after MeHg exposure;
      rather, we propose that ROS formation is a downstream event that reflects MeHg
      induced mitochondrial dysfunction due to increased mitochondrial calcium levels.

PMID- 17442396
TI  - Pasteurella meningo-encephalitis--a risk of household pets.

PMID- 17442398
TI  - Computerized measurement of facial expression of emotions in schizophrenia.
AB  - Deficits in the ability to express emotions characterize several neuropsychiatric
      disorders and are a hallmark of schizophrenia, and there is need for a method of
      quantifying expression, which is currently done by clinical ratings. This paper
      presents the development and validation of a computational framework for
      quantifying emotional expression differences between patients with schizophrenia
      and healthy controls. Each face is modeled as a combination of elastic regions,
      and expression changes are modeled as a deformation between a neutral face and an
      expressive face. Functions of these deformations, known as the regional
      volumetric difference (RVD) functions, form distinctive quantitative profiles of
      expressions. Employing pattern classification techniques, we have designed
      expression classifiers for the four universal emotions of happiness, sadness,
      anger and fear by training on RVD functions of expression changes. The
      classifiers were cross-validated and then applied to facial expression images of
      patients with schizophrenia and healthy controls. The classification score for
      each image reflects the extent to which the expressed emotion matches the
      intended emotion. Group-wise statistical analysis revealed this score to be
      significantly different between healthy controls and patients, especially in the
      case of anger. This score correlated with clinical severity of flat affect. These
      results encourage the use of such deformation based expression quantification
      measures for research in clinical applications that require the automated
      measurement of facial affect.

PMID- 17442399
TI  - Panic disorder and suicidality: is comorbidity with depression the key?
AB  - BACKGROUND: The relation between panic disorder and suicidal behavior has been
      surrounded by perennial controversy. A significant number of reports suggest that
      PD is associated with suicidal behavior. Alternatively, it has been proposed that
      comorbid depression may account for the increased suicidality identified in this
      population. METHOD: A total of n=474 consecutive psychiatric outpatient subjects
      were assessed for Axes I and II psychopathology and personality traits, as well
      as suicidal behavior, using structured interviews. RESULTS: Approximately half of
      the sample (n=250) reported suicidal ideation, either lifetime or during the 6
      months prior to evaluation. In total, 200 subjects reported a history of suicide
      attempts. When comorbidity with depressive disorders (DD) was not taken into
      account, patients with Panic Disorder (PD) did not differ from those with a
      primary diagnosis of depressive disorder in terms of age, current or lifetime
      suicide ideation or number of suicide attempts. After separating the group
      characterized by PD comorbid with DD, PD only subjects had significantly lower
      number of suicide attempts compared to either DD (p<0.01) or comorbid PD-DD
      (p<0.05). Similar levels of SI were noted between PD, DD and PD-DD, both current
      and lifetime. Suicide attempters with PD, DD or both did not differ in terms of
      suicide intent or lethality. They were also similar on impulsivity, aggressive
      behavior and state-trait anxiety measures. LIMITATIONS: Cross-sectional design,
      the limited sample size in the PD only group, retrospectively collected data with
      the possibility of recall bias. CONCLUSIONS: In this clinical outpatient sample,
      the association between panic disorder and suicidal behavior was primarily
      explained by comorbidity with depressive disorders. No differences were observed
      between different groups for measures of severity of the suicidal behavior.
      Physicians should be aware of these associations when assessing adults with panic
      disorder for suicidality.

PMID- 17442400
TI  - Prophylactic treatment response in bipolar disorder: results of a naturalistic
      observation study.
AB  - BACKGROUND: The objective of this study was to evaluate effectiveness of commonly
      used prophylactic treatments for bipolar disorder in a naturalistic setting and
      to explore factors associated with treatment response. METHODS: We reviewed
      charts of 120 patients with a confirmed diagnosis of bipolar I or bipolar II
      disorder. The sample consisted of 37 males and 83 females, in the age range of 20
      to 81 years (mean age 45+/-14 years), treated at an outpatient psychiatry program
      in a teaching hospital. In contrast to controlled clinical trials, we did not
      exclude subjects with co-morbid conditions and/or substance abuse. Treatment
      outcome was evaluated using a scale for retrospective assessment of prophylactic
      treatment response. The scale rates the degree of improvement in the course of
      treatment weighted by the likelihood of response being attributable to the
      treatment. The inter-reliability of the assessments was good with concordance of
      ratings of 90% and weighted kappa of 0.8. RESULTS: Rates of full response to
      individual mood stabilizers were: lithium 30%, carbamazepine 0%, valproate 13%,
      lamotrigine 11%, and olanzapine 25%. Lithium responders were more likely to be
      bipolar II, and had a typically episodic course of illness with earlier onset in
      comparison with non-responders. Responders to valproate had higher rates of
      psychosis. LIMITATIONS: Data were obtained by chart reviews. CONCLUSIONS: Less
      than one-third of patients treated with lithium achieved remission; the
      effectiveness of other treatments in this naturalistic sample was even lower.

PMID- 17442401
TI  - Exercise tolerance is reduced in bipolar illness.
AB  - BACKGROUND: Cardiovascular and cerebrovascular disease is 2-3 times more common
      in bipolar patients than the general population. Asymptomatic bipolar patients
      have electrocardiogram abnormalities at high rates. The question of heart
      function in asymptomatic bipolar subjects arises. METHODS: This study examined
      the impact of exhaustive exercise on cardiac function in untrained euthymic
      bipolar and control subjects. Twenty-four non-athletic adults, 10 controls and 14
      with bipolar type I, exercised on a treadmill at 70% of maximal oxygen
      consumption until physical exhaustion. Two-dimensional and Doppler
      echocardiography were performed before and immediately after exercise. RESULTS:
      Bipolar subjects had significantly reduced exercise duration (75.9+/-40.5min for
      bipolar and 95.0+/-40.1 min for control, P<0.01). There were no statistical
      differences between bipolar illness and normal controls in echocardiographic
      variables either at rest or after exhaustive exercise. CONCLUSION: Medically
      asymptomatic, euthymic bipolar subjects appear to have reduced exercise tolerance
      but normal cardiac function. LIMITATIONS: More bipolar patients smoked (28.6% vs.
      0% controls) and patients tended to be heavier (189.1+/-29.3 vs. 165.0+/-29.5 lb,
      t=2.0, P=0.06). None of the normal controls were taking any medications. These
      variables could have impacted the reduced exercise tolerance.

PMID- 17442402
TI  - Memory and executive functioning in obsessive-compulsive disorder: a selective
      review.
AB  - BACKGROUND: The neurocognitive deficits that underlie the unique features of
      obsessive-compulsive disorder (OCD) are not yet completely understood. This paper
      reviews the main neuropsychological findings in memory and executive functioning
      in this disorder, and examines a number of challenges facing this area of
      research. METHOD: A selective review of the neuropsychological literature on OCD
      was conducted using MEDLINE and drawing on literature known to the authors.
      RESULTS: The neuropsychological profile of OCD appears to be one of primary
      executive dysfunction. Although memory functioning may be affected, these
      deficits appear secondary to an executive failure of organizational strategies
      during encoding. On tasks of executive functioning patients with OCD demonstrate
      increased response latencies, perseveration of responses, and difficulties
      utilizing feedback to adapt to change. LIMITATIONS: A statistical meta-analysis
      was not performed and only the cognitive domains of memory and executive
      functioning were examined. CONCLUSIONS: Given the prominence of chronic doubt and
      indecision in clinical settings, it is surprising that decision making as a
      cognitive construct as related to OCD has not received greater attention in the
      neuropsychological literature. On the basis of emerging literature we suggest
      that it is a potential area of dysfunction and one that warrants further
      investigation as it may assist in enhancing our understanding of the
      pathophysiology of OCD.

PMID- 17442403
TI  - Early second-trimester inflammatory markers and short cervical length and the
      risk of recurrent preterm birth.
AB  - This study aimed to analyze the associations between serum and cervicovaginal
      inflammatory markers and recurrent spontaneous preterm birth in a cohort study of
      62 pregnant women with > or =1 prior early spontaneous birth. Serum samples and
      cervicovaginal swabs from the women were obtained at enrollment in early second
      trimester (week 12-25). Cervical length was measured by ultrasound and
      dicotomized in to short (< or =25 mm) and long cervices (>25 mm). The study
      endpoints were spontaneous preterm birth before 35 weeks and secondarily<37
      weeks. Multiple inflammatory markers in serum (IL-1beta, IL-2, IL-5, IL-6, IL-8,
      IL-12, IL-18, TNF-alpha, TGF-beta, sTNF-R1, GM-CSF and TREM-1) and cervicovaginal
      secretions (IL-18, sTNF-RI and sIL-6) were individually associated with
      spontaneous preterm birth. Short cervical length did not explain associations
      between inflammatory markers and spontaneous preterm birth. Serum and
      cervicovaginal inflammatory markers did not correlate. In a combined prediction
      model using both serum and vaginal inflammatory markers, serum TNF-alpha,
      cervicovaginal sIL-6Ralpha and cervical length predicted 69% of all recurrent
      spontaneous preterm birth at a 5% false-positive rate. In conclusion, cervical
      length, serum TNF-alpha and cervicovaginal sIL-6Ralpha provide a clinically
      useful prediction of recurrent preterm birth in early second-trimester in women
      with a prior spontaneous preterm birth.

PMID- 17442404
TI  - Marking of peripheral T-lymphocytes by retroviral transduction and
      transplantation of CD34+ cells in a canine X-linked severe combined
      immunodeficiency model.
AB  - A retrovirus vector containing an enhanced green fluorescent protein
      complimentary DNA (EGFP cDNA) was used to mark and dynamically follow vector
      expressing cells in the peripheral blood of bone marrow transplanted X-linked
      severe combined immunodeficient dogs. CD34(+) cells isolated from young normal
      dogs were transduced, using a 2 day protocol, with an amphotropic retroviral
      vector that expressed enhanced green fluorescent protein (EGFP) and the canine
      common gamma chain (gammac) cDNAs. Following transplantation of the transduced
      cells, normal donor peripheral blood lymphocytes (PBL) appeared by 1 month post
      bone marrow transplant (BMT) and rescued three of five treated dogs from their
      lethal immunodeficiency. PCR and flow cytometric analysis of post-BMT PBL
      documented the peripheral EGFP expressing cells as CD3(+) T cells, which varied
      from 0% to 28%. Sorting of EGFP(+) and EGFP(-) peripheral blood T cells from two
      dogs, followed by vector PCR analysis, showed no evidence of vector shutdown.
      EGFP expression in B cells or monocytes was not detected. These marking
      experiments demonstrate that the transduction protocol did not abolish the
      lymphoid engraftment capability of ex vivo transduced canine CD34(+) cells and
      supports the potential utility of the MSCV retroviral vector for gene transfer to
      XSCID affected canine hematopoietic progenitor cells (HPC).

PMID- 17442406
TI  - COX-2 inhibitors ameliorate experimental autoimmune encephalomyelitis through
      modulating IFN-gamma and IL-10 production by inhibiting T-bet expression.
AB  - The COX-2 inhibitors Rofecoxib (Rof) and Lumiracoxib (Lum) were evaluated in
      experimental autoimmune encephalomyelitis (EAE), the model of multiple sclerosis
      (MS). Administration of Rof and Lum significantly reduced the incidence and
      severity of EAE, which was associated with the inhibition of MOG 35-55 lymphocyte
      recall response, anti-MOG 35-55 T cell responses, and modulation of cytokines
      production. In vitro Rof and Lum inhibited primary T cells proliferation and
      modulated cytokine production. These findings highlight the fact that Rof and Lum
      likely prevents EAE by modulating Th1/Th2 response, and suggest its utility in
      the treatment of MS and other autoimmune diseases.

PMID- 17442405
TI  - beta(2)-Adrenergic receptor-dependent sexual dimorphism for murine leukocyte
      migration.
AB  - In wild-type FVB mice, leukocyte recruitment to lipopolysaccharide was sexually
      dimorphic, with a greater number of leukocytes recruited in females. In male
      beta(2)-adrenergic receptor knock out mice (bred on a congenic FVB background)
      the number of leukocytes recruited was increased approximately 4-fold, while in
      females there was no change, eliminating sexual dimorphism in leukocyte
      migration. While there were significantly fewer recruited CD62L(+) and CD11a(+)
      leukocytes in wild-type males, only in male beta-adrenergic receptor knock out
      mice was there an increase in the number of recruited CD11a(+) leukocytes, again
      eliminating sexual dimorphism. Thus, leukocyte migration and CD11a(+) adhesion
      molecule expression in male, but not in female, leukocytes is beta-adrenergic
      receptor-dependent. Our findings provide support for a role of beta(2)-adrenergic
      receptor mechanisms in the inflammatory response, and suggest that beta(2)
      adrenergic receptor on male leukocytes contributes to sexual dimorphism in the
      effect of stress on inflammatory diseases.

PMID- 17442407
TI  - Tumor associated release of interleukin-10 alters the prolactin receptor and down
      regulates prolactin responsiveness of immature cortical thymocytes.
AB  - The soluble factors produced either by Ehrlich's ascites carcinoma (EAC) or
      thymic adherent cells (TAC) of tumor-bearing mice comprising of CD11b(+) and
      CD11c(+) antigen-presenting cells caused a sharp decrease in prolactin (PRL)
      induced ConA-mediated effect on survival of PNA(+) thymocytes. Similar
      suppression of PRL-induced effect was observed when the cells were cocultured
      with TAC of EAC-bearing mice. Anti-IL-10 antibody could reverse the PRL inability
      to induce ConA-mediated effect on PNA(+) thymocyte survival, indicating the
      presence of IL-10 in EAC culture supernatant (EAC sup) and thymic
      microenvironment. IL-10 could block PRL-induced proliferation of PNA(+)
      thymocytes without affecting spontaneous apoptosis. IL-10 altered the expression
      of the long-form (LF) of PRL-R and reduced the PRL binding of the cells,
      suggesting down-regulation of the PRL effect on PNA(+) thymocyte by the cytokine.
      Induction of tumor, which was found to increase the IL-10 secretion by TAC, also
      modified the PRL-R (LF) to PRL-R (SF). Since PRL plays a role in survival,
      proliferation and differentiation of lymphoid progenitor cells, the tuning of PRL
      action by IL-10 may be a possible mechanism of depletion of immature cortical
      thymocytes and thymic atrophy in tumor-bearing mice.

PMID- 17442408
TI  - Maxillofacial trauma of pediatric patients in Malaysia: a retrospective study
      from 1999 to 2001 in three hospitals.
AB  - OBJECTIVE: Maxillofacial trauma in children is not common worldwide. Domestic
      injuries are frequently seen in younger children while older children are mostly
      involved in motor vehicle accidents (MVA). The objective of this study was to
      analyze the pattern of maxillofacial injuries in pediatric patients referred to
      three government main hospitals in different areas of West Malaysia. METHODS:
      Patients' records of three selected hospitals in Malaysia (National University of
      Malaysia Hospital, Kajang Hospital and Seremban Hospital) from January 1999 to
      December 2001 were reviewed. Data associated with demographics, etiology of
      injury in relation to age group, type of injuries whether soft tissues of hard
      tissue in relation to age group and treatment modalities were collected. RESULTS:
      A total of 521 pediatric patients' records were reviewed. Malays made up the
      majority of patients with maxillofacial injuries in the three hospitals. Males
      outnumbered females in all the three hospitals. Injuries commonly occur in the 11
      16 years old. MVA was the most common etiology followed by fall and assault. Soft
      tissue injuries were the most common type of injuries in all the hospitals. In
      relation to fractures, mandible was the most common bone to fracture with condyle
      being the most common site. Orbital fracture was the most common fracture in the
      midfacial area. Most of the fractures were managed conservatively especially in
      the younger age groups. Open reduction with or without internal fixation was more
      frequently carried out in the 11-16 years old group. CONCLUSION: Children exhibit
      different pattern of clinical features depending on the etiology and stage of
      their bone maturation. A dedicated team, who is competent in trauma and aware of
      the unique anatomy, physical and psychological characteristics of children,
      should manage pediatric patient with trauma.

PMID- 17442409
TI  - Tioman virus infection in experimentally infected mouse brain and its association
      with apoptosis.
AB  - Tioman virus is a newly described bat-urine derived paramyxovirus isolated in
      Tioman Island, Malaysia in 2001. Hitherto, neither human nor animal infection by
      this virus has been reported. Nonetheless, its close relationship to another
      paramyxovirus, the Menangle virus which had caused diseases in humans and pigs
      [Philbey, A.W., Kirkland, P.D., Ross, A.D., Davis, R.J., Gleeson, A.B., Love,
      R.J., Daniels, P.W., Gould, A.R., Hyatt, A.D., 1998. An apparently new virus
      (family Paramyxoviridae) infectious for pigs, humans, and fruit bats. Emerg.
      Infect. Dis. 4, 269-271], raises the possibility that it may be potentially
      pathogenic. In this study, mice were experimentally infected with Tioman virus by
      intraperitoneal and intracerebral routes, and the cellular targets and
      topographical distribution of viral genome and antigens were examined using in
      situ hybridization and immunohistochemistry, respectively. The possible
      association between viral infection and apoptosis was also investigated using the
      TUNEL assay and immunohistochemistry to FasL, Caspase-3, Caspase-8, Caspase-9 and
      bcl-2. The results showed that Tioman virus inoculated intracerebrally was
      neurotropic causing plaque-like necrotic areas, and appeared to preferentially
      replicate in the neocortex and limbic system. Viral infection of inflammatory
      cells was also demonstrated. TUNEL and Caspase-3 positivity was found in
      inflammatory cells but not in neurons, while FasL, Caspase-8 and Caspase-9 were
      consistently negative. This suggests that neuronal infection was associated with
      necrosis rather than apoptosis. Moreover, the data suggest that there may be an
      association between viral infection and apoptosis in inflammatory cells, and that
      it could, at least in part, involve Caspase-independent pathways. Bcl-2 was
      expressed in some neurons and inflammatory cells indicating its possible role in
      anti-apoptosis. There was no evidence of central nervous system infection via the
      intraperitoneal route.

PMID- 17442410
TI  - Molecular basis of antagonism between K70E and K65R tenofovir-associated
      mutations in HIV-1 reverse transcriptase.
AB  - The K70E mutation in HIV-1 reverse transcriptase was observed in 10% of virologic
      non-responders of the abacavir/lamivudine/tenofovir arm of ESS30009, alone, or in
      mixtures with K65R by population sequencing. Clonal analysis of six ESS30009 K70E
      isolates failed to identify double mutants carrying K65R+K70E. Site-directed K70E
      mutants had a replication capacity of 97+/-29%, but only 2.4+/-0.9% for K65R+K70E
      and 0.01% for K65R+K70E+M184V mutants. K65R+K70E phenotypic fold changes for
      abacavir, lamivudine and tenofovir were comparable to reported values for K65R
      alone. In molecular dynamic simulations, the epsilon-amino group of K65 was
      positioned 2.7+/-0.1A from the gamma-phosphate of the dTTP ligand and stabilized
      the triphosphate. In the R65 mutant, this distance increased to 4.2+/-0.4A and
      the interaction energy with the ligand was less favorable, but the K70 epsilon
      amino group was repositioned closer to the gamma-phosphate and had a more
      favorable interaction energy. In the double mutant, E70 could not stabilize the
      gamma-phosphate, resulting in a more severe defect. The net effect of the atomic
      level changes in the double mutant may be to destabilize the pyrophosphate
      leaving group of the ligand, more severely affecting the catalytic rate of the
      polymerization reaction than the R65 single mutation.

PMID- 17442411
TI  - Marked differences in response to dopamine receptor antagonism in two rat
      mutants, ci2 and ci3, with lateralized rotational behavior.
AB  - We have recently described two rat mutants, ci2 and ci3, in which abnormal
      lateralized rotational behavior and locomotor hyperactivity occur either
      spontaneously or in response to external stimuli, such as new environment. While
      cochlear and vestibular defects are found in ci2 rats, ci3 rats do not exhibit
      any inner ear abnormalities. Both mutants show abnormal lateralities in striatal
      dopamine and in the density of dopaminergic neurons in substantia nigra or
      ventral tegmental area, which may be involved in the behavioral phenotype of
      these rats. In line with this hypothesis, the circling behavior of the ci2 and
      ci3 mutants is intensified by amphetamine. In the present study, we evaluated the
      effects of dopamine receptor blockade on the abnormal behaviors of ci2 and ci3
      rats. Haloperidol blocked the hyperactivity in both mutants, but this was most
      likely due to the known inhibitory effect on locomotion by this drug. When
      animals were observed during the light phase, the abnormal rotational behavior of
      the mutants was not significantly affected by haloperidol, whereas the dopamine
      D2 receptor-preferring antagonist raclopride significantly reduced rotations in
      ci2 rats. When the behavior of the ci3 rats was video-monitored during the dark
      phase, circling was significantly inhibited by haloperidol. The most striking
      difference between the two mutants was that ci2 rats were less susceptible than
      the unaffected littermates to the cataleptogenic effects of haloperidol and
      raclopride, whereas no such difference was observed in ci3 rats. These data
      demonstrate that, although there are several similarities between the ci2 and ci3
      rat mutants, their cataleptogenic response to dopamine receptor blockade
      strikingly differs. The comparative evaluation of these two rat mutants may help
      to increase our understanding of the relationship between developmental anomalies
      of cerebral asymmetry and brain disorders.

PMID- 17442412
TI  - Dietary copper exposure in the African walking catfish, Clarias gariepinus:
      transient osmoregulatory disturbances and oxidative stress.
AB  - There are few dietary Copper (Cu) toxicity studies on warm water fish. We used
      the African walking catfish (Clarias gariepinus) to perform the first in vivo
      dietary Cu toxicity study on this species. We measured end points normally
      associated with metal toxicity (nutritional performance, haematology, histology,
      tissue Cu, Na(+), and K(+), Na(+)K(+)-ATPase activity) and add to the limited
      data on oxidative stress during dietary Cu exposure (thiobarbituric acid reactive
      substances or TBARS, and total glutathione). Clarias gariepinus were fed to
      satiation on a Cu-loaded diet (1500 mg Cu kg(-1)dw feed), or a control diet (15
      mg Cu kg(-1) dw feed), for 30 days. Dietary copper exposure caused elevated Cu
      concentrations in the intestine (20 fold), liver (5 fold) and gills (4 fold) of
      Cu-exposed fish compared to controls after 30 days (ANOVA, P<0.05). Copper
      exposed fish showed a reduction in food intake and specific growth rate (SGR),
      but only very modest reductions in mean body mass at the end of the experiment
      (the latter not statistically significant). There were no treatment-dependent
      effects on food conversion ratio or proximate composition, and only transient
      disturbances to tissue electrolytes and Na(+)K(+)-ATPase activity. Haematology
      was normal throughout the experiment. Cu-exposed fish showed an increase in TBARS
      in the gill (1.5 fold) and intestine (2 fold increase) compared to the controls
      (ANOVA or Kruskal-Wallis, P<0.05). Total glutathione content in the intestine of
      Cu-exposed fish doubled by the end of the experiment compared to controls,
      reaching 12.7+/-2.85 micromol g(-1) wet weight (mean+/-S.E.M., n=6, Student's t
      test, P<0.05). The liver showed some glycogen depletion consistent with reduced
      food intake, but no overt pathologies in the gills, liver or intestine were
      observed.

PMID- 17442413
TI  - The surface protein Pvs25 of Plasmodium vivax ookinetes interacts with
      calreticulin on the midgut apical surface of the malaria vector Anopheles
      albimanus.
AB  - Malaria parasite transmission-blocking control strategies within the mosquito
      vector require an adequate understanding of the parasite mosquito interaction at
      the molecular level. The ookinete P25-P28 surface proteins are required for the
      transition from ookinete to oocyst in the mosquito midgut; however, their
      respective molecular interactions in the mosquito are largely unknown. We used
      recombinant Pvs25 and Pvs28 as probes for identification of potential Anopheles
      albimanus midgut ligands. A 50 kDa protein interacted with Pvs25 but not with
      Pvs28 in blot overlay assays. This protein was identified as calreticulin by LS
      MS and was detected in membrane, but not in soluble midgut protein extracts.
      Calreticulin was detected in An. albimanus midgut microvilli by
      immunofluorescence analysis. The An. albimanus calreticulin cDNA was cloned and
      recombinant calreticulin was shown to interact with recombinant Pvs25 in overlay
      and co-immunoprecipitation assays, confirming the interaction of the two
      proteins. The Pvs25-calreticulin interaction in vivo could represent a potential
      target for developing transmission blocking strategies based on interfering the
      parasite-midgut interaction.

PMID- 17442414
TI  - RAF kinases and mitochondria.
AB  - Over the past decade, several investigators reported that a fraction of the RAF
      kinases are recruited to the mitochondria. Although we are still far from a
      global understanding of the molecular consequences of RAF translocation on
      mitochondrial physiology and metabolism, the recent description of some molecular
      interactions that are established by C-RAF in this organelle, principally with
      the proteins Bcl-2 and Bag-1, provides some clues. Here, we discuss the possible
      contribution of RAF targeting to mitochondria to their modulation of apoptosis
      signaling, as well as to this organelle's physiology. In addition, we discuss the
      possible modulation of the mitochondrial metabolism by RAF oncogenes in the
      context of cancer.

PMID- 17442415
TI  - Hypoxia alters the adhesive properties of lymphatic endothelial cells. A
      transcriptional and functional study.
AB  - Recent advances in our understanding of the molecular biology of lymphatic
      endothelial cells have revealed that these vessels, besides their known function
      in tissue homeostasis and immunity, constitute conduits for the tumor cells to
      metastasize. One of the factors that contribute to tumor spread is the
      acquisition of an angiogenic phenotype as a response to the onset of tumor
      hypoxia. To our knowledge, little is known about the effects of low oxygen levels
      on the lymphatic vasculature. Therefore, we used cDNA microarrays to study the
      transcriptional changes occurring in hypoxia exposed lymphatic endothelial cells.
      Our analysis was then complemented by functional assays showing that these cells
      responded with increased attachment to the extracellular matrix, delayed
      proliferation and production of reactive oxygen species. Differential expression
      of genes involved in these processes such as NADPH oxidase 4, the tissue
      inhibitor of metalloproteinase 3, and TGFbeta induced protein I, was found.
      Hypoxia was also found to increase mRNA levels of the cytokine CXCL-12 and its
      receptor CXCR4. Moreover, adhesion experiments revealed that hypoxia increased
      the binding of non-small cell lung carcinoma cells to this endothelium in a CXCR4
      dependent way. We thus illustrate the response of lymphatic endothelial cells to
      hypoxia and suggest targets to study tumor metastasis through these vessels.

PMID- 17442416
TI  - KCNQ channels are involved in the regulatory volume decrease response in primary
      neonatal rat cardiomyocytes.
AB  - Cardiomyocytes may experience significant cell swelling during ischemia and
      reperfusion. Such changes in cardiomyocyte volume have been shown to affect the
      electrical properties of the heart, possibly leading to cardiac arrhythmia. In
      the present study the regulatory volume decrease (RVD) response of neonatal rat
      cardiomyocytes was studied in intact single cells attached to coverslips, i.e.
      with an intact cytoskeleton. The potential contribution of KCNQ (Kv7) channels to
      the RVD response and the possible involvement of the F-actin cytoskeleton were
      investigated. The rate of RVD was significantly inhibited in the presence of the
      KCNQ channel blocker XE-991 (10 and 100 microM). Electrophysiological experiments
      confirmed the presence of an XE-991 sensitive current and Western blotting
      analysis revealed that KCNQ1 channel protein was present in the neonatal rat
      cardiomyocytes. Hypoosmotic cell swelling changes the structure of the F-actin
      cytoskeleton, leading to a more rounded cell shape, less pronounced F-actin
      stress fibers and patches of actin. In the presence of cytochalasin D (1 microM),
      a potent inhibitor of actin polymerization, the RVD response was strongly
      reduced, confirming a possible role for an intact F-actin cytoskeleton in linking
      cell swelling to activation of ion transport in neonatal rat cardiomyocytes.

PMID- 17442417
TI  - Double chambered right ventricle: depiction at three-dimensional whole heart
      magnetic resonance imaging.
AB  - Double chambered right ventricle (DCRV) is a rare form of congenital heart
      disease in which the right ventricle is divided into a high-pressure inlet site
      and a low-pressure outlet site by anomalous muscle bands. Whole heart magnetic
      resonance imaging (MRI) which depicts 3-dimensional anatomy of the heart and
      coronary arteries was useful to diagnose DCRV.

PMID- 17442418
TI  - Influence of left ventricular filling pattern on exercise-induced changes of
      natriuretic peptides in patients with suspected coronary artery disease.
AB  - BACKGROUND: Exertional change in brain natriuretic peptide (BNP) has recently
      been proposed as a biomarker of myocardial ischemia. However, in patients with
      abnormal left ventricular (LV) filling, BNP is frequently increased. Therefore,
      we studied the relationship of exertional changes in atrial and brain natriuretic
      peptides (ANP and BNP) with resting and exercise-induced changes of LV systolic
      function and filling pattern. METHODS: LV function at rest and peak exercise was
      assessed in 140 patients (mean age 65 years, 78 men) during symptom-limited
      exercise echocardiography for evaluation of suspected coronary artery disease.
      ANP and BNP were measured at rest and 5 min after exercise. RESULTS: ANP and BNP
      increased with exercise. The increase in BNP was significantly greater in the 65
      patients with than in the 76 patients without ischemia [14.7 pg/ml (5.7-19.6) vs.
      4.9 pg/ml (2.1-9.2), p<0.0001]; there was no difference in increase of ANP [340
      pg/ml (176-729) vs. 424 pg/ml (249-648), p=0.54]. The exertional rise in BNP was
      also greater in patients with abnormal LV filling at rest [10.5 pg/ml (4.9-19.6)
      vs. 4.1 pg/ml (2.0-6.7), p<0.0001]. By multivariate linear regression, exertional
      change in wall motion score index (beta=0.23, p<0.001), baseline BNP (beta=0.71,
      p<0.001), abnormal LV filling pattern (beta=0.24, p<0.001) and age (beta=-0.15,
      p=0.02) were predictors of change in BNP. CONCLUSIONS: In patients with suspected
      coronary artery disease, exertional changes of BNP are related not only to
      ischemia, but also to the LV filling pattern at rest.

PMID- 17442419
TI  - Catheter-based management for the congenital coronary arteriovenous fistula
      indicated by the stress 99mTc-MIBI SPECT.
AB  - A 10-year-old boy, who had suffered Kawasaki disease 7 years ago, presented chest
      pain, pale face, and cold sweating in the stress (99m)technetium
      methoxyisobutylisonitrile ((99m)Tc-MIBI) single-photon emission computed
      tomography (SPECT), which showed reversible perfusion abnormality indicative of
      myocardial ischemia involving the right coronary artery. Angiography identified
      congenital coronary arteriovenous fistula (CAVF) from the right coronary artery
      to the main pulmonary artery, to which the patient's symptoms and signs of
      myocardial ischemia, by means of coronary steal phenomenon that entails
      reversible perfusion abnormality in the stress (99m)Tc-MIBI SPECT, could be
      ascribed. The penny shall finally be dropped without sudden cardiac event after
      coaxial transarterial coil occlusion on this boy with the congenital CAVF that is
      indicated significantly by the stress (99m)Tc-MIBI SPECT.

PMID- 17442420
TI  - White-coat effect and blood pressure reactivity.

PMID- 17442421
TI  - Ventricular fibrillation after a hymenoptera sting.
AB  - A 54-year-old male, who had presented 2 ventricular fibrillation (VF) episodes
      with post-anoxic coma and later a return to consciousness and to a sinusal rhythm
      after defibrillation, have been placed a ventricular intracavitary stimulator
      (AICD). Since all the tests including the coronarygraphy have been found normal,
      we have paid attention to the anamnesis revealing an Apis mellifera sting before
      both VF episodes, previously considered irrelevant for the absence of relevant
      local symptoms. Intracutaneous tests were negative to Vespula sp. and positive to
      A. mellifera extract at a concentration of 0.01 mug/ml. Specific IgE for A.
      mellifera venom presented values of 2,36 U/ml for A. mellifera and <0.35 U/ml per
      Vespula sp. and Polistes dominulus. The patient was then submitted to ITS with A.
      mellifera aqueous extract. During the RASH treatment no adverse reactions have
      been observed, whereas we witnessed a major adverse reaction, 3 min after the
      first 100 mcg maintenance dose, controlled with anti-H1 and cortisone reaction,
      nevertheless no reactions were observed during the 3 years the same dosage has
      been repeated monthly. Our case supports the hypothesis of an anaphylactic
      reaction as trigger of vasoconstriction in individuals affected by ventricular
      arrhythmia not explained with other causes such as a coronary disease, a
      myocardiopathy or a pharmacological toxicity. Arrhythmia can be a serious
      outbreak of a mediated IgE allergic reaction even without any relevant local
      symptoms. The diagnostics with lyophilized A. mellifera venom has been proven
      safe in a patient who suffered a cardiac anaphylaxis.

PMID- 17442422
TI  - Assessment of left atrial volume and function by real-time three-dimensional
      echocardiography.
AB  - BACKGROUND: Determination of left atrial (LA) size and function is important in
      clinical decision-making. Calculation of LA volume (LAV) is the most accurate
      index of LA size. AIM: To compare real-time 3-dimensional echocardiography
      (RT3DE) and 2-dimensional echocardiography (2DE) for calculation of LAV and
      function. METHODS: Fifty patients were studied using 2DE and RT3DE for
      calculating LAV including: Maximum (V max), minimum (V min) and pre-atrial
      contraction (V pre A) volumes. For 2DE, the formula: LAV=8(A1) (A2)/3pi (L) was
      used, while for RT3DE, offline analysis was performed using commercially
      available software. LA function indices including Total Atrial Stroke Volume
      (TASV), active ASV (AASV), Total Atrial Emptying Fraction (TAEF), active AEF
      (AAEF), passive AEF (PAEF), and Atrial Expansion Index (AEI) were calculated.
      RESULTS: Patients were classified into 2 equal groups: group I with normal V max
      (< 50 ml) and group II with V max (> or = 50 ml). Good correlation was obtained
      between RT3DE and 2DE for LAV (r=0.64, p=0.001) in group I and (r=0.83, p<0.0001)
      in group II. In group I, LAV and functions showed no significant difference by
      both techniques, while in group II, the V min and V pre A were significantly
      lower by RT3DE than 2DE (p=0.009, 0.006). TAEF, AEI, and PAEF indices were
      significantly higher by RT3DE than 2DE in group II. CONCLUSION: RT3DE provides a
      reproducible assessment of active and passive LA function by volumetric cyclic
      changes. It is comparable and may be superior to 2DE due to its higher
      sensitivity to volume changes.

PMID- 17442423
TI  - Isolated noncompaction of the ventricular myocardium in a 94-year-old patient:
      depiction at echocardiography and magnetic resonance imaging.
AB  - A 94-year-old man presented with episodes of transient ischemic attack.
      Echocardiography showed prominent trabeculations and deep intratrabecular
      recesses in the anterior and lateral left ventricular segments. Cine magnetic
      resonance imaging showed a double-layered appearance on the 4-chamber view and
      marked trabeculations and intratrabecular recesses in the infero-lateral segments
      on the short axis view. These findings were consistent with those of isolated
      noncompaction of the ventricular myocardium (INVM). This is the oldest patient
      with INVM ever reported previously.

PMID- 17442424
TI  - The incidence, treatment strategies and outcomes of acute coronary syndromes in
      the "reperfusion network" of different hospital types in the Czech Republic:
      results of the Czech evaluation of acute coronary syndromes in hospitalized
      patients (CZECH) registry.
AB  - AIMS: To analyze the incidence, treatment strategies and outcomes of acute
      coronary syndromes (ACS) in Czech population. METHODS AND RESULTS: ACS diagnosis
      was confirmed in 1345 of 1921 (70%) consecutively admitted patients with
      suspected ACS. ACS incidence was 3248 cases/million/year and the annual incidence
      of confirmed myocardial infarction was 1960 per million. In-hospital mortality
      was 5.1% (10.0% with Q-MI, 4.4% with non-Q-MI, and 0.9% with UAP). Coronary
      angiography was performed in 92% of STEMI (followed by primary PCI in 83%, by
      CABG in 3%, by conservative therapy in 6%). Thrombolysis was used in only 1% of
      patients. Reperfusion therapy was thus used in 87% of all STEMI patients.
      Discharge medication included aspirin in 95%, a statin in 76%, a beta-blocker in
      78%, an ACE inhibitor in 50%, clopidogrel in 60%, and ticlopidine in 4% of
      patients. CONCLUSIONS: In-hospital mortality of ACS in the Czech network of PCI
      and non-PCI hospitals is low. Nationwide application of primary PCI strategy for
      STEMI is feasible and increases the overall use of reperfusion therapy.

PMID- 17442425
TI  - The role of repeating optimization of atrioventricular interval during interim
      and long-term follow-up after cardiac resynchronization therapy.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective therapy for
      heart failure patients with electromechanical delay. Optimization of
      atrioventricular interval (AVI) is a cardinal component for the benefits.
      However, it is unknown if the AVI needs to be re-optimized during long-term
      follow-up. METHODS: Thirty-one patients (66+/-11 years, 20 males) with sinus
      rhythm who received CRT underwent serial optimization of AVI at day 1, 3-month
      and during long-term follow-up by pulse Doppler echocardiography (PDE). At long
      term follow-up, the optimal AVI and cardiac output (CO) estimated by non-invasive
      impedance cardiography (ICG) were compared with those by PDE. RESULTS: The follow
      up was 16+/-11 months. There was no significant difference in the mean optimal
      AVI when compared between any 2 time points among day 1 (99+/-30 ms), 3-month
      (97+/-28 ms) and long-term follow-up (94+/-28 ms). However, in individual
      patient, the optimal AVI remained unchanged only in 14 patients (44%), and was
      shortened in 12 (38%) and lengthened in 6 patients (18%). During long-term follow
      up, although the mean optimal AVIs obtained by PDE or ICG (94+/-28 vs. 92+/-29
      ms) were not different, a discrepancy was found in 14 patients (45%). For the
      same AVI, the CO measured by ICG was systematically higher than that by PDE
      (3.5+/-0.8 Vs. 2.7+/-0.6 L/min, p<0.001). CONCLUSION: Optimization of AVI after
      CRT appears necessary during follow-up as it was readjusted in 55% of patients.
      Although AVI optimization by ICG was feasible, further studies are needed to
      confirm its role in optimizing AVI after CRT.

PMID- 17442426
TI  - Sexual behavior and reproductive concerns among adolescents and young adults with
      congenital heart disease.
AB  - OBJECTIVES: To examine the sexual behaviors and reproductive concerns among
      patients with moderate to complex congenital heart disease (CHD). BACKGROUND:
      There is a growing need to understand and address the psychosocial issues for
      older adolescents and young adults with CHD. Emerging sexuality is an issue for
      this age group and pregnancy for many women with CHD is risky. But, patients'
      sexual behavior and reproductive concerns have not been studied. METHODS: Young
      adults (19-20 years old; n=212) and adolescents (16-18 years old; n=144) with
      moderate to complex CHD reported their sexual behaviors and reproductive
      concerns. Data were compared to normative samples from Canada and the United
      States. RESULTS: Few adolescents (14%) but many young adults (48%) with CHD were
      sexually active (at least one partner in the previous 3 months). These rates were
      lower than those of their healthy peers. Among the sexually active patients, 36%
      of the young adults and 72% of the adolescents engaged in one or more types of
      potentially risky sexual behavior (i.e., two or more partners in the past 3
      months, questionable birth control, using drugs or alcohol before sex at least
      sometimes). Women with complex CHD had the highest levels of concern regarding
      their fertility and risk of genetic transmission of CHD, as well as concerns
      about adverse effects of pregnancy on their own health. CONCLUSIONS: Sexual
      health should be discussed with adolescents and young adults with CHD. Particular
      attention should be given to discussing sexual health with women who have complex
      CHD.

PMID- 17442427
TI  - Is the use of ABPM justified in patients on 1 or 2 antihypertensive medications?
AB  - We studied the utility of ABPM in patients with elevated clinic BP on 1-2
      antihypertensive medications (group B, N=117), compared with those on no
      medications (group A, N=76) and on > or =3 medications (group C, N=110). 35% of
      patients in group B had adequately controlled 24-h BP based on ABPM, compared
      with 22.4% in group A (P=0.06) and 19.1% in group C (P=0.007). Antihypertensive
      treatment was not escalated in patients with adequately controlled BP. This
      suggests that ABPM has an important role in therapeutic decision-making for
      patients on 1-2 antihypertensive medications.

PMID- 17442428
TI  - Cytokines, interstitial collagen and ventricular remodelling in dilated
      cardiomyopathy.
AB  - BACKGROUND: Dilated cardiomyopathy (DCM) is associated with myocardial fibrosis,
      and proinflammatory cytokines may play a role in this. METHODS: N-terminal type I
      and III procollagen propeptides (PINP, PIIINP) and cross-linked telopeptide of
      type I collagen (ICTP) were measured from serum samples of 73 patients with DCM
      and 56 age and sex matched controls. Circulating cytokine levels were determined
      in DCM patients. RESULTS: Serum levels of PINP and PIIINP were lower in patients
      than in controls (p<0.05 and p=0.001). In patients with DCM, the levels of PIIINP
      and ICTP correlated significantly with each other (p<0.01), and the
      proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha) and
      interleukin-6 (IL-6), correlated positively with ICTP (p<0.001, p<0.05),
      PIIINP/PINP ratio (p<0.05, p<0.01) and left atrial size (p<0.01, p<0.05).
      Presence of atrial fibrillation was associated with lower serum PINP level and
      higher PIIINP/PINP ratio (p<0.05). CONCLUSIONS: Our results suggest that
      interstitial myocardial collagen metabolism is altered in DCM patients and
      regulated by proinflammatory cytokines. These changes in collagen metabolism are
      associated with presence of atrial fibrillation, but do not reflect left
      ventricular remodelling. Treatment with beta-blockers and inhibitors of the renin
      angiotensin aldosterone system seem to effectively inhibit overall type I and III
      collagen syntheses.

PMID- 17442429
TI  - Interleukin-8 as an independent predictor of long-term clinical outcome in
      patients with coronary artery disease.
AB  - BACKGROUND: Accumulating evidence suggests that inflammation plays an essential
      role in the pathogenesis of atherosclerosis and that circulating inflammatory
      markers predict future cardiovascular events. However, previous studies evaluated
      the predictive value of only a single cytokine at a time. AIMS: This study was
      designed to simultaneously measure plasma levels of multiple cytokines in
      patients with coronary artery disease and to evaluate their ability to predict
      long-term prognosis. METHODS: The study enrolled 158 consecutive patients with
      angiographically identified stable coronary artery disease. Using the Luminex
      micro-beads array system, we simultaneously measured plasma levels of the
      following 10 cytokines: interleukin (IL)-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL
      10, tumor necrosis factor (TNF)-alpha, granulocyte-macrophage colony stimulating
      factor (GM-CSF) and gamma-interferon (IFN-gamma). RESULTS: None of the 10
      cytokine levels as well as high-sensitive C reactive protein (hs-CRP) was
      correlated with the severity of coronary artery disease. During a 7-year follow
      up period, cardiovascular events occurred in 56 patients (35%). Multi-vessel
      disease, diabetes, and high levels of all of the 10 measured cytokines and hs-CRP
      were significant predictors of cardiovascular events in univariate analysis.
      However, multivariate analysis using multi-vessel disease, diabetes and the
      levels of all of 10 cytokines and hs-CRP showed that the only independent
      predictor was IL-8 (RR, 2.98; 95%CI, 1.64-7.24; P=0.0001). CONCLUSION: IL-8 was
      the only cytokine that predicted cardiovascular events independent of the other 9
      cytokines and hs-CRP. Since IL-8 is a neutrophil chemokine, these results suggest
      that neutrophil activation may be related to the occurrence of cardiovascular
      events.

PMID- 17442430
TI  - Sudden death in a patient with lamin A/C gene mutation and near normal left
      ventricular systolic function.
AB  - Mutations in the lamin A/C gene seem to be important aetiological factors in
      familial DCM. Heart disease caused by lamin A/C gene mutations is characterised
      by conduction system disorders with the need for permanent pacemaker
      implantations, atrial fibrillation, severe heart failure, and increased risk for
      sudden cardiac death. We described an asymptomatic 28-year-old man with a R190W
      lamin A/C gene mutation and mild left ventricular enlargement and near normal
      left ventricular ejection fraction who suffered from sudden cardiac death during
      sleeping. His electrocardiogram did not show conduction system disease and the
      most remarkable finding was a progressive decrease in voltage, which may be a
      marker of disease progression. The case study's mother had a similar phenotype to
      this and also had died suddenly. Sudden cardiac death in some lamin A/C gene
      mutations may occur even before the development of severe left ventricular
      dysfunction and implantable cardioverter-defibrillator should be early
      considered.

PMID- 17442431
TI  - Cor triatriatum presenting in adulthood: a case report.
AB  - Cor triatriatum is a rare congenital defect in which a fibromuscular membrane
      divides the left atrium into two distinct chambers. We described a case of cor
      triatriatum with interesting Doppler flow signal in a 39-year-old female. The
      diagnosis was confirmed on cardiac catheterization and surgery.

PMID- 17442432
TI  - Intravascular ultrasound findings in patients with restenosis of sirolimus- and
      paclitaxel-eluting stents.
AB  - OBJECTIVE: We used intravascular ultrasound (IVUS) to compare restenotic
      sirolimus-eluting (SES) vs paclitaxel-eluting (PES) stents. BACKGROUND: Little is
      known about the IVUS pattern and mechanisms of restenosis, in the two widely
      available drug-eluting stent (DES) platforms. METHODS: Volumetric IVUS analysis
      was performed in patients with clinical restenosis in DES (n=29 SES and 11 PES
      respectively). RESULTS: Despite similar vessel volumes (347.5+/-155.6 vs 356.5+/
      164.1 mm(3), p=0.84) and stent volumes (175.6+/-74.57 vs 179.7+/-84.24 mm(3),
      p=1.0), IVUS analysis showed that neointimal hyperplasia volume was significantly
      greater in PES restenoses than in SES restenoses (40.0+/-44.2 vs 19.3+/-11.4
      mm(3), p=0.02) without any significant difference in distribution over the stent
      length. This leads to a higher percent of volume obstruction (intimal hyperplasia
      volume divided by stent volume: 18.5+/-13.7% vs 11.8+/-7.7%, p=0.045). Minimal
      stent area was smaller in SES than in PES (4.3+/-1.2 vs 5.6+/-1.2 mm(2), p=0.06)
      and stent underexpansion was more frequently observed in SES stents: minimal
      stent area <4.5 mm(2) (65% in SES vs 27% in PES, p=0.04). Stent edge restenosis
      occurred in 1/29 SES (3%) vs 3/11 PES (27%) stents, p=0.056. CONCLUSION: The
      magnitude of neointimal hyperplasia was greater in PES than in SES while stent
      underexpansion appeared to be more common in SES.

PMID- 17442433
TI  - Visualization of transplanted cells within the myocardium.
AB  - Intra-myocardial and intra-coronary transplantation of somatic stem cells as a
      therapy of heart failure is currently under clinical evaluation. A major
      limitation of all clinical studies dealing with myocardial cell engraftment is
      the inability to track the fate of the transplanted cells. This would be crucial
      for the scientific interpretation and monitoring of possible contribution of
      engrafted cells to improved cardiac function. We present an overview of all
      publications focusing on promising novel technologies that may allow for short-
      and long-term follow up of transplanted cells by visualization. Clinicians should
      consider appropriate bioimaging methods for in vivo visualization of engrafted
      cells in the heart when designing clinical studies.

PMID- 17442434
TI  - Involvement of thymus in amiodarone-treated autoimmune myocarditis in rats.
AB  - We previously showed that amiodarone, an iodine-rich benzofuranic derivative,
      interferes with the progression of myocarditis using a rat model of experimental
      autoimmune myocarditis. Further studies have also revealed that intraperitoneal
      treatment with 12.5 mg/kg amiodarone, which is below the range of its therapeutic
      plasma concentration, also effectively interferes with the progression of
      myocarditis using the same model. The relationship between myocarditis and the
      thymus has not been studied in either patients or animal models. To investigate
      whether the thymus is involved in the effect of amiodarone on experimental
      autoimmune myocarditis, we examined its phenotypic distribution in thymocytes and
      peripheral blood lymphocytes using flow cytometry. We found no significant
      differences in the proportions of CD4(+) and CD8(+) T cells and the CD4(+)/CD8(+)
      T cell ratio in the control group compared with amiodarone-treated group.
      However, amiodarone-treated group induced a decrease in the proportion of
      CD4(+)TNF(+) and CD4(+)IL-4(+) T cells and an increase in CD4(+)IFN(+) T cells,
      resulting in a significant reduction of the CD4(+)TNF(+)/CD4(+)IFN(+) and
      CD4(+)IL-4(+)/CD4(+)IFN(+) T cell ratios. These results suggest for the first
      time that the thymus is actively involved when myocarditis is treated with
      amiodarone.

PMID- 17442435
TI  - The dilemma in diagnosing double right coronary artery: contribution of
      multidetector computed tomography.

PMID- 17442436
TI  - Exercise-induced myocardial ischemia in a patient with dislocated right coronary
      artery orifice in the right sinus of Valsalva.
AB  - Anomalous origin of the right coronary artery (RCA) is a rare congenital anomaly,
      which may cause myocardial ischemia and sudden death. In most cases, the RCA
      orifice is located in the left sinus of Valsalva and the RCA courses between the
      great arteries. We report a case in whom the RCA orifice is located in the right
      sinus of Valsalva but myocardial ischemia in the territory of the RCA was induced
      by exercise. Multidetector-row computed tomography showed that the RCA orifice
      was located in the right sinus of Valsalva adjacent to the left sinus of Valsalva
      and the RCA coursed between the great arteries. Compression of the RCA by the
      great arteries during exercise was thought to be the major cause of myocardial
      ischemia.

PMID- 17442437
TI  - Left ventricular noncompaction with a single coronary artery of anomalous origin.
AB  - Noncompaction of ventricular myocardium (NVM) is a morphogenetic anomaly of
      ventricular myocardium that leads to the development of cardiomyopathy. It is
      frequently associated with other congenital cardiac malformations. A 75-year-old
      woman was admitted with resting dyspnea lasting for several days. Two-dimensional
      echocardiography demonstrated an enlarged left ventricle with global impairment
      of systolic function. The myocardial trabeculations, with multiple recesses, were
      observed at the apex and mid-ventricular segment of the left ventricle. Contrast
      echocardiography showed filling of the recesses with the contrast agent. Dynamic
      contrast magnetic resonance imaging also showed distinctive features of NVM
      corresponding to the echocardiographic findings. In addition, a coronary artery
      originating from the proximal ascending aorta was observed. Aortogram and
      coronary angiography confirmed that the coronary artery had an aberrant origin
      from the ascending aorta and right coronary artery was an anomalous origin from
      left anterior descending coronary artery. This case suggests that NVM can present
      with other life threatening cardiovascular anomalies and different imaging
      studies are helpful for a comprehensive diagnosis.

PMID- 17442438
TI  - Lapse of care as a predictor for morbidity in adults with congenital heart
      disease.
AB  - BACKGROUND: There is a need for timely transition of patients with congenital
      heart disease who have reached adulthood. While the American Heart Association
      guidelines dictate that patients with moderate or great complexity lesions be
      seen at least every 2 years, lapse in care is common. We sought to assess the
      frequency and clinical impact of lapse of medical care in adults with moderate or
      great complexity cardiac lesions diagnosed in childhood. METHODS: All patients,
      fulfilling the above criteria, who were seen in an Adult Congenital Heart Disease
      regional clinic from 2002 to 2005 were questioned as to the length of time from
      leaving care at a pediatric institution to establishment of subsequent cardiac
      care. Lapse of medical care, defined as > or = 2 year interval from leaving a
      pediatric cardiac care facility, was determined. Variables associated with lapse
      of medical care were sought. Variables associated with adverse outcome were
      identified. RESULTS: Of 400 patients seen, 158 met inclusion criteria. Of these,
      lapse of medical care was present in 99 (63%) with a median duration of lapse of
      medical care of 10 (2-50 years). The most common reason cited for lapse of
      medical care was that the patient was told there was no need for follow-up (32%).
      Patients with lapse of medical care were 3.1x(p=0.003) more likely to require
      urgent cardiac intervention (p=0.003). CONCLUSIONS: Lapse of medical care is
      common in adults with congenital heart disease and is associated with adverse
      outcome.

PMID- 17442439
TI  - Routine fluorescence in situ hybridization in soil.
AB  - The use of fluorescence in situ hybridization (FISH) to identify and enumerate
      soil bacteria has long been hampered by the autofluorescence of soil particles
      masking the bacterial signals and because the need of counting hundreds of
      bacteria in order to achieve statistically reliable data is time consuming.
      Recently, it was demonstrated that Nycodenz facilitates FISH in soil by
      concentrating bacteria on membrane filters and avoiding autofluorescent soil
      particles. We present a routine protocol for FISH in soil including the use of
      Nycodenz. The protocol allows fast and easy enumeration of hundreds of bacteria.
      We propose the use of silicon grease coated slides to treat in parallel seven
      samples per hybridization. Further, we developed a semi-automated approach for
      the enumeration of bacteria by implementing macros concatenating all steps of the
      image analyzes in the Image J software. Using Nycodenz, software-assisted
      bacterial counts statistically matched eye-counts of the same images and it was
      possible to count 880 DAPI stained bacteria per ten images. Fifty-five percent of
      these bacteria were co-labelled with the FISH probe specific for the Domain
      Bacteria, in accordance with recent FISH studies of bacterial populations in bulk
      soil. With a soil slurry protocol used for comparison, soil particles impaired
      automatic counts of the bacteria and FISH analysis, and only 88 DAPI stained
      bacteria per ten images could be counted by eye. With the Nycodenz protocol, 5 mM
      Na(2)EDTA used as an extractant increased the number of bacteria observed by 49%.
      In contrast, Tween 20 (1% or 5%) had no significant effect and increased the
      variability between the samples. Overall, the proposed procedure allows to
      process a high number of samples and to achieve a time efficient FISH
      characterization of soil bacterial communities.

PMID- 17442440
TI  - Oscillatory responses representing differential auditory processing in sleep.
AB  - The goal of the study was to investigate the contribution of the delta and theta
      responses to the peaks on the event-related potential waveform and specifically
      to find the possible cognitive correlates of these oscillatory responses in rapid
      eye movements (REM) sleep and Stage 2 (spindle sleep), Stage 3 (light sleep) and
      Stage 4 (deep sleep; slow wave sleep) of non-REM sleep. Data on overnight sleep
      was acquired from 12 healthy, young adult, volunteer males; those on awake stage
      were obtained from 19 matched males. Brain activity was obtained in response to
      auditory stimuli (2000 Hz deviant and 1000 Hz standard stimuli: 65 dB, 10 ms r/f
      time, 50 ms duration) under passive oddball paradigm in sleep, active and passive
      oddball (OB-a, OB-p, respectively) paradigms in wakefulness. The effect of the
      experimental variables (stimulus type, sleep stage) was studied using 2 x 4
      analysis of variance for repeated measures and stepwise multiple regression
      analysis. Overall, three types of configurations were obtained for the
      oscillatory responses which varied according to sleep stage and stimulus type:
      Large amplitude, differentiated delta and distinct theta response of long
      duration; distinct theta response with short duration; distinct delta response.
      As in wakefulness, the morphology of the time-domain peaks was found to be due to
      the superposition of the delta and theta responses. The configuration in REM
      resembled the responses to the OB-p paradigm and that NREM stages resembled the
      responses to the OB-a paradigm in wakefulness. Auditory information processing
      selectively varied according to sleep stages and took longer in sleep. Comparable
      peaks were obtained at longer latencies and later components appeared that did
      not exist under wakefulness. With respect to the long-duration theta activity,
      and greater differentiation between the deviant- and standard-elicited stimuli,
      Stage 2 appeared to represent the more effortful cognitive processing.

PMID- 17442441
TI  - Increasing the yield of MCL-PHA from nonanoic acid by co-feeding glucose during
      the PHA accumulation stage in two-stage fed-batch fermentations of Pseudomonas
      putida KT2440.
AB  - A method was developed to increase the yield of MCL-PHA from nonanoic acid in the
      PHA accumulation phase. Pseudomonas putida KT2440 was grown on glucose until
      ammonium-limitation was imposed. In the second (accumulation) stage, either
      glucose, nonanoic acid, or a mixture of these carbon and energy sources was
      supplied. Since the medium-chain-length poly-3-hydroxyalkanoate (MCL-PHA)
      subunits produced are unique for each carbon source, their relative contribution
      to PHA yield could be calculated. Y(C7+C9)/NA was 0.254 mol mol(-1) during PHA
      synthesis from nonanoic acid. Y(C8+C10)/G was only 0.057 mol mol(-1) during PHA
      synthesis from glucose. When nonanoic acid and glucose were fed together,
      Y(C7+C8)/NA almost doubled to 0.450 mol mol(-1) while Y(C8+C10)/G decreased to
      0.011 mol mol(-1). These results demonstrate that substantial savings can be
      obtained by feeding glucose with substrates that are good for PHA production but
      much more expensive than glucose.

PMID- 17442442
TI  - Novel cationic vesicle platform derived from vernonia oil for efficient delivery
      of DNA through plant cuticle membranes.
AB  - Novel cationic amphiphilic compounds were prepared from vernonia oil, a natural
      epoxidized triglyceride, and studied with respect to vesicle formation,
      encapsulation of biomaterials such as DNA, and their physical stability and
      transport through isolated plant cuticle membranes. The amphiphiles studied were
      a single-headed compound III (a quaternary ammonium head group with two alkyl
      chains) and a triple-headed compound IV, which is essentially three molecules of
      compound III bound together through a glycerol moiety. Vesicles of the two
      amphiphiles, prepared by sonication in water and solutions of uranyl acetate or
      the herbicide 2,4-D (2,4-dichloropenoxy acetic acid), were examined by TEM, SEM,
      AFM, and confocal laser systems and had a spherical shape which encapsulated the
      solutes with diameters between 40 and 110 nm. Vesicles from amphiphile IV could
      be made large enough to encapsulate a condensed 5.2kb DNA plasmid (pJD328).
      Vesicles of amphiphile IV were also shown to pass intact across isolated plant
      cuticle membranes and the rate of delivery of encapsulated radio-labeled 2,4-D
      through isolated plant cuticle membranes obtained with these vesicles was clearly
      greater in comparison to liposomes prepared from dipalmitopyl phosphatidylcholine
      (DPPC) and the control, nonencapsulated 2,4-D. Vesicles from amphiphiles III and
      IV were found to be more stable than those of liposomes from DPPC. The data
      indicate the potential of vesicles prepared from the novel amphiphile IV to be a
      relatively efficient nano-scale delivery system to transport DNA and other
      bioactive agents through plant biological barriers. This scientific approach may
      open the way for further development of efficient in vivo plant transformation
      systems.

PMID- 17442443
TI  - Rice black-streaked dwarf virus outer capsid protein P10 has self-interactions
      and forms oligomeric complexes in solution.
AB  - The P10 protein encoded by S10 ORF of Rice black-streaked dwarf virus (RBSDV) was
      thought to be the component of outer shell of viral particle. In the present
      study, P10 has an ability for self-interaction as shown by a GAL4 transcription
      activator-based yeast two-hybrid assay system and further confirmed by in vitro
      far-Western blot analysis. The domain responsible for P10-P10 self-interaction
      was mapped to the first 230 amino acids at the N-terminal region of the protein.
      The oligomerization property of P10 was further investigated using chemical cross
      linking with purified recombinant P10 proteins expressed in a baculovirus
      expression system and glutaraldehyde. Intact P10 recombinants existed
      predominantly as trimers in solution in the absence of other viral proteins and
      displayed the oligomeric nature common to all known second-layer protein units of
      the Reoviridae. A truncated P10 mutant encoding the first 230 N-terminal amino
      acids lost its ability to form trimers even though dimeric forms were detected
      during the cross-linking assay. Polyacrylamide gel electrophoresis under reducing
      or non-reducing conditions suggested that P10 subunits were oligomerized not
      through intermolecular disulfide bonds, but perhaps through some other type of
      association, such as hydrophobic or charge interactions.

PMID- 17442444
TI  - Prediction of oral absorption of griseofulvin, a BCS class II drug, based on GITA
      model: utilization of a more suitable medium for in-vitro dissolution study.
AB  - The in-vivo absorbability of drugs categorized into the biopharmaceutics
      classification system (BCS) class II is very difficult to be predicted because of
      the large variability in the absorption and/or dissolution kinetics and the lack
      of an adequate in-vitro system for evaluating the dissolution behavior. We tried
      to predict the in-vivo absorption kinetics of griseofulvin, categorized into BCS
      class II, orally administrated as powders into rats, based on Gastrointestinal
      Transit-Absorption model (GITA model), consisting of the absorption, dissolution
      and GI-transit processes. Using the dissolution rate constants (k(dis)) of
      griseofulvin obtained with JP 1st solution, JP 2nd solution, FaSSIF, FeSSIF and
      modified SIBLM as a medium, simulation lines were not able to describe the
      observed mean plasma profile at all. On the other hand, a calculated line
      provided by employing k(dis) obtained with MREVID 2 (medium reflecting in-vivo
      dissolution 2), a new medium, was in better agreement with the observed mean
      plasma profile than existing media, indicating that the utilization of adequate
      k(dis) value made it possible to predict the in-vivo absorption kinetics of drugs
      classified into BCS class II based on GITA model and that MREVID 2 could be a
      useful medium for describing the in-vivo dissolution kinetics.

PMID- 17442445
TI  - Coevolution of genomic intron number and splice sites.
AB  - Spliceosomal intron numbers and boundary sequences vary dramatically in
      eukaryotes. We found a striking correspondence between low intron number and
      strong sequence conservation of 5' splice sites (5'ss) across eukaryotic genomes.
      The phylogenetic pattern suggests that ancestral 5'ss were relatively weakly
      conserved, but that some lineages independently underwent both major intron loss
      and 5'ss strengthening. It seems that eukaryotic ancestors had relatively large
      intron numbers and 'weak' 5'ss, a pattern associated with frequent alternative
      splicing in modern organisms.

PMID- 17442446
TI  - Systemic siRNA delivery via hydrodynamic intravascular injection.
AB  - The main barrier to the use of RNAi in mammalian systems is the difficulty in
      delivering siRNA or shRNA to the appropriate tissues. Although progress has been
      made in this area, many of the technologies developed require specialized
      expertise and reagents that are beyond the reach of most investigators. In
      contrast, the hydrodynamic injection technique is simple to perform and enables
      highly efficient delivery of naked, unmodified siRNA to a number of tissues,
      especially the liver. This review describes the development of the technique and
      explores the possible mechanisms that enable uptake of siRNA to biological
      effect. Examples of the use of hydrodynamic injection in animal models of disease
      and for the study of gene function are presented and discussed.

PMID- 17442447
TI  - A phase II study of irinotecan (CPT-11) and carboplatin in patients with limited
      disease small cell lung cancer (SCLC).
AB  - PURPOSE: The aim of this phase II trial was to evaluate the efficacy and safety
      of a combination chemotherapy containing irinotecan (CPT-11) and carboplatin as
      first-line treatment of patients with small cell lung cancer (SCLC). PATIENTS AND
      METHODS: From December 2002 to May 2004 61 patients with limited disease (IASLC
      classification) were enrolled who were not suitable for concurrent chemo
      radiotherapy. Eighteen of the 61 patients (29.5%) had malignant pleural or
      pericardial effusion and 4 patients (6.6%) had involved supra- or infraclavicular
      lymph nodes. Patients received irinotecan 50mg/m(2) on days 1, 8 and 15 and
      carboplatin AUC 5 on day 1, every 4 weeks. RESULTS: A total of 233 chemotherapy
      cycles were administered. The median number of cycles per patient was 4. The
      overall response rate to chemotherapy on an intention-to-treat basis was 64%. The
      median overall survival was 13.8 months, the median disease-free survival 8.0
      months, the 1-year survival rate 53.5%, and the 2-year survival rate 17.9%.
      Haematological and non-hematogical toxicities were low (CTC-grade 3 neutropenia
      14.8%, grade 3 thrombocytopenia 5.2%, grade 3/4 anemia 5.1%, grade 3
      nausea/vomiting 5.1%, grade 3 diarrhea 3.6%, grade 3 alopecia 3.6% of pts).
      CONCLUSION: The results suggest that the combination of irinotecan (CPT-11) and
      carboplatin is active and well tolerable in patients with limited disease SCLC
      who were not suitable for concurrent chemotherapy.

PMID- 17442448
TI  - Simultaneous expression of c-erbB-1, c-erbB-2, c-erbB-3 and c-erbB-4 receptors in
      non-small-cell lung carcinomas: correlation with clinical outcome.
AB  - The expression of c-erbB receptors was immunohistochemically examined in paraffin
      embedded specimens from non-small-cell lung carcinomas. A total of 209 patients
      were enrolled [squamous-cell carcinomas (n=59), adenocarcinomas (n=130), large
      cell carcinomas (n=15) and giant-cell carcinomas (n=5)]. The HercepTest kit
      scoring guidelines were used for the interpretation of positivity. C-erbB-1 was
      overexpressed in older patients, in squamous-cell carcinomas and in poorly
      differentiated tumours, whereas c-erbB-2 overexpression with adenocarcinomas and
      poorly-differentiated tumours. C-erbB-4 overexpression correlated with advanced
      disease stage. The c-erbB-1/4 pair was the most commonly overexpressed and
      significantly correlated with female gender, while the c-erbB-1/2 pair with older
      age. Response to chemotherapy was significantly reduced in patients with tumours
      overexpressing c-erbB-1 receptor as well as the c-erbB-1/2 and c-erbB-3/4
      receptor pairs. Patients' overall survival was significantly correlated with the
      co-expression of c-erbB-1 and c-erbB-4 receptors. These findings clearly suggest
      that specific receptors overexpression or co-overexpression is correlated with
      patients' disease control rate and outcome. A better understanding of the
      overexpression of the heterodimerized partners of c-erbB family receptors may
      provide a useful predictive indicator of response to molecular targeted therapies
      with c-erbB inhibitors.

PMID- 17442449
TI  - Post-operative respiratory rehabilitation after lung resection for non-small cell
      lung cancer.
AB  - BACKGROUND: To investigate the efficacy of an inpatient Pulmonary Rehabilitation
      program (i-PR) after lung resection (LR) for Non-Small Cell Lung Cancer (NSCLC).
      PATIENTS AND METHODS: From January 2001 to December 2004, 211 out of 618 patients
      who underwent LR were considered eligible for i-PR. Twenty-five patients accepted
      the i-PR and were included in the case group. The remaining 186 who refused i-PR
      were taken as controls. RESULTS: The two study groups were comparable for
      demographic and surgical characteristics, as well as for the peri-operative
      morbidity (4% in the controls and 3% among patients undergoing i-PR). Most
      functional parameters among treated patients were improved when baseline versus 1
      month figures were compared, despite the strong correction for multiple
      comparison limited statistical significance to Borg scale dyspnoea on exertion -
      median - (2 versus 0; p<0.01); pH (7.45 versus 7.42; p<0.05); timed walk-6MWD
      (297.8m versus 393.4m; p<0.01) and Hb saturation during 6MWD (95.4% versus 93.9%;
      p<0.05). On the contrary, global function in the group of controls was
      homogeneously decreased (FEV(1) and PEF p<0.01) after operation. The comparison
      of treated and untreated patients 1 month after the operation did not show any
      significant difference in terms of FEV(1), FVC, PEF, distance, Hb saturation, and
      KCO that instead were homogeneously and significantly worse at baseline (before
      the surgical operation) in the case group. CONCLUSIONS: Respiratory Function and
      exercise capacity significantly improve following a post-operative 4-week i-PR in
      lung resected patients. i-PR could be regarded as a component of the management
      of patients who have undergone LR for cancer.

PMID- 17442450
TI  - Lung cancer outcomes at a UK cancer unit between 1998-2001.
AB  - There are few data published on lung cancer survival in the UK. Survival rates
      for lung cancer at a UK Hospital between 1998-2001 are described. METHODS:
      Analysis of data collected from multidisciplinary team (MDT) meetings, lung
      cancer registrations and hospital coding. RESULTS: 835 new lung cancers were
      diagnosed comprising 597 non-small cell lung cancers (NSCLC) (71%), 133 small
      cell (SCLC) (16%), and 105 clinical diagnoses (13%). Stage at diagnosis; stage I
      (25%), II (9%), IIIA (8%), IIIB (23%), IV (35%). Surgery was undertaken in 12%,
      radical radiotherapy (RT) in 4%, palliative RT in 32%, chemotherapy in 8% and
      best supportive care (BSC) in 36%. The 3-year cumulative survival for NSCLC was:
      stage I 39%, stage II 30%, stage III 6%, stage IV 0.5%. Only 46% of patients with
      stage I-IIIA disease received radical treatment. Reasons included poor lung
      function (32%), unresectable (24%), co-morbidities (17%), performance status
      (8%), patient choice (8%), unclear (6%), advanced age (5%). CONCLUSIONS: Survival
      figures are similar to other UK studies but do not compare favourably with US and
      European data. This may be because a large proportion of patients with early
      stage disease receive palliative care only.

PMID- 17442451
TI  - Uranium removal from groundwater via in situ biostimulation: Field-scale modeling
      of transport and biological processes.
AB  - During 2002 and 2003, bioremediation experiments in the unconfined aquifer of the
      Old Rifle UMTRA field site in western Colorado provided evidence for the
      immobilization of hexavalent uranium in groundwater by iron-reducing Geobacter
      sp. stimulated by acetate amendment. As the bioavailable Fe(III) terminal
      electron acceptor was depleted in the zone just downgradient of the acetate
      injection gallery, sulfate-reducing organisms came to dominate the microbial
      community. In the present study, we use multicomponent reactive transport
      modeling to analyze data from the 2002 field experiment to identify the dominant
      transport and biological processes controlling uranium mobility during
      biostimulation, and determine field-scale parameters for these modeled processes.
      The coupled process simulation approach was able to establish a quantitative
      characterization of the principal flow, transport, and reaction processes based
      on the 2002 field experiment, that could be applied without modification to
      describe the 2003 field experiment. Insights gained from this analysis include
      field-scale estimates of the bioavailable Fe(III) mineral threshold for the onset
      of sulfate reduction, and rates for the Fe(III), U(VI), and sulfate terminal
      electron accepting processes.

PMID- 17442452
TI  - Open-label trial of cyclosporine for vulvar lichen sclerosus.
AB  - BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory disease of skin and
      mucosal surfaces which is generally difficult to treat. OBJECTIVE: We evaluated
      the efficacy of oral cyclosporine in refractory vulvar LS. METHODS: Five patients
      with refractory vulvar LS were treated with oral cyclosporine (3-4 mg/kg/d) for 3
      months. They were followed up on a monthly basis. RESULTS: At the end of the
      treatment, the mean total symptom score regressed significantly and clinical
      findings such as erythema and erosion showed marked improvement. Mild adverse
      effects were seen in 3 patients. LIMITATIONS: The patients did not give consent
      to rebiopsy at the end of the treatment. CONCLUSION: Moderate dose of oral
      cyclosporine could be an effective alternative in the treatment of refractory
      vulvar LS.

PMID- 17442453
TI  - Influence of a negative movie message on food perceptions.
AB  - Many food scholars have suggested that popular media messages impact perceptions
      of foods. In the present study, experimental participants watched a disparaging
      video clip concerning McDonald's foods as well as a ruse video clip, then were
      asked to evaluate the healthfulness of 33 named foods as well as their nutrient
      descriptions. Control participants judged the named foods and their descriptions
      but saw no videos. The movie clip influenced only named foods that are
      identifiable with McDonalds and not other fast foods or other named foods that
      are considered unhealthy.

PMID- 17442454
TI  - Growing up poor: long-term implications for eating patterns and body weight.
AB  - This study aimed to understand how poverty-associated food deprivation in
      childhood contributes to the well-known relationship between low socioeconomic
      status (SES) in childhood and obesity in the adult years. Thirty low-income,
      rural women with at least one child were followed for over three years with
      annual semi-structured interviews collecting quantitative and qualitative data.
      For the quantitative portion, the measures of interest were body mass index
      (BMI), food insecurity, eating patterns, and SES. For the qualitative portion,
      text from the interviews was analyzed using the constant comparative method.
      Growing up in a poor household was associated with increased risk of overweight
      and obesity in adulthood. Experiences of poverty-associated food deprivation in
      childhood appeared to super-motivate some women to actively avoid food insecurity
      in adulthood. It also influenced the women's current food preferences. Tremendous
      excitement accompanied the availability of food after periods of deprivation in
      both the women and their children. Some women had used food to meet emotional
      needs in childhood and overeating had become a generalized response to negative
      emotional states in the adult years. Food deprivation in childhood and associated
      attitudes and behaviors towards food are one possible mechanism for explaining
      the association between childhood poverty and adult obesity.

PMID- 17442455
TI  - Public acceptance of nanotechnology foods and food packaging: the influence of
      affect and trust.
AB  - Nanotechnology is increasingly being employed in the areas of food production and
      packaging. Public perception will be crucial to the realization of these
      technological advances. We examined how lay people (N=153) perceive
      nanotechnology foods and nanotechnology food packaging, and we examined the
      factors that influence willingness to buy these products. Participants received
      some general information about nanotechnology, and specific information about
      four nanotechnology applications. Overall, participants were hesitant to buy
      nanotechnology foods or food with nanotechnology packaging. Results suggest,
      however, that nanotechnology packaging is perceived as being more beneficial than
      nanotechnology foods. Results further suggest that social trust in the food
      industry is an important factor directly influencing the affect evoked by these
      new products. As suggested by the affect heuristic, affect had an impact on
      perceived benefits and perceived risks. Perceived benefit seems to be the most
      important predictor for willingness to buy.

PMID- 17442456
TI  - TrkB but not trkC receptors are necessary for postnatal maintenance of
      hippocampal spines.
AB  - Dendritic spines are major sites of excitatory synaptic transmission and changes
      in their densities have been linked to alterations in learning and memory. The
      neurotrophins brain-derived neurotrophic factor and neurotrophin-3 and their
      receptors, trkB and trkC, are thought to be involved in learning, memory and long
      term potentiation (LTP). LTP is known to induce trkB and trkC gene expression as
      well as spinogenesis in the hippocampus. In the aging hippocampus, declines in
      trkB and trkC mRNA levels may underlie, at least in part, impairments in spatial
      memory and reductions in spine densities. To determine the significance of trkB
      and trkC for the maintenance of dendritic spines, we have analyzed Golgi
      impregnated hippocampi of adult and aged mice heterozygous for trkB, trkC, or
      both along with respective wildtype littermates. Deletion of one allele of trkB,
      but not trkC, significantly reduces spine densities of CA1 pyramidal neurons in
      both adult and aged mice, as compared to age-matched controls. This indicates
      that trkB, but not trkC, receptors are necessary for the maintenance of
      hippocampal spines during postnatal life.

PMID- 17442457
TI  - No association of dynamin binding protein (DNMBP) gene SNPs and Alzheimer's
      disease.
AB  - A recent scan of single nucleotide polymorphisms (SNPs) on chromosome 10q found
      significant association of six correlated SNPs with late-onset Alzheimer's
      disease (AD) among Japanese. We examined the SNP with the highest statistical
      significance (rs3740058) in a large Caucasian American case-control cohort and
      the remaining five SNPs in a smaller subset of cases and controls. We observed no
      association of statistical significance in either the total sample or the APOE*4
      non-carriers for any of the SNPs.

PMID- 17442458
TI  - Alpha v integrins mediate beta-amyloid induced inhibition of long-term
      potentiation.
AB  - Beta-amyloid (Abeta) is the principal component of the extracellular plaques
      present in patients with Alzheimer's disease. Several studies have recently shown
      that acutely applied Abeta inhibits the induction of LTP in the hippocampus. In
      the present studies, we have investigated the role of integrins in such Abeta
      mediated block of LTP in the dentate gyrus in vitro and in the CA1 in vivo.
      Selective antibodies to the alpha v integrin subunit were found to prevent the
      Abeta inhibition of LTP, both in the dentate gyrus in vitro and in the CA1 in
      vivo. In contrast, two control antibodies did not prevent such action of Abeta.
      In addition, a small molecule nonpeptide antagonist of alpha v-containing
      integrins and two other antagonistic ligands of integrins, superfibronectin and
      the disintegrin echistatin, also prevented the Abeta inhibition of LTP. These
      studies indicate that alpha v integrins may be important mediators of synaptic
      dysfunction prior to neurodegeneration in Alzheimer's disease.

PMID- 17442459
TI  - Exploring three-dimensional quantitative structural activity relationship (3D
      QSAR) analysis of SCH 66336 (Sarasar) analogues of farnesyltransferase
      inhibitors.
AB  - 3D-QSAR analysis of a set of 37 analogues of SCH 66336 (Sarasar) was performed by
      most widely used computational tool, molecular field analysis (MFA) to
      investigate the substitutional requirements for the favorable receptor-drug
      interaction and to derive a predictive model that may be used for the designing
      of a novel farnesyltransferase inhibitors (FTIs). Regression analysis was carried
      out using genetic partial least squares (G/PLS) method. A highly predictive and
      statistically significant model was generated. The predictive ability of the
      model developed was assessed using a test set of six compounds (r(2)(pred) as
      high as 0.791). The analyzed MFA model has demonstrated a good fit, having r(2)
      value of 0.967 and cross-validated coefficient r(2)(cv) value as 0.921.

PMID- 17442460
TI  - Synthesis, characterization and antiamoebic activity of new indole-3
      carboxaldehyde thiosemicarbazones and their Pd(II) complexes.
AB  - In continuation of our research on thiosemicarbazones and their metal complexes
      as antiamoebic agents, a new series of indole-3-carboxaldehyde thiosemicarbazones
      (TSC) 1-7 were prepared by condensing indole-3-carboxaldehyde with
      cycloalkylaminothiocarbonyl hydrazines. Their palladium(II) complexes of the
      [Pd(TSC)Cl2] type, were synthesized upon coordination with [Pd(DMSO)2Cl2]. The
      chemical structures of all the compounds were established by elemental analyses,
      electronic, IR, (1)H NMR and (13)C NMR spectral data. The structure of the
      complexes was further established by thermogravimetric analysis and FAB MS.
      Spectroscopic data revealed that thiosemicarbazones act as bidentate ligands,
      making use of thione sulphur and azomethine nitrogen atom for coordination to the
      Pd(II) ion. Among all the compounds evaluated for antiamoebic activity using
      HM1:IMSS strain of Entamoeba histolytica, all palladium complexes were found to
      be more active than their respective ligands. Moreover, ligand 5 and complexes 1a
      3a, 5a and 7a showed antiamoebic activity, at lower IC(50) doses when compared to
      the reference drug metronidazole with IC(50)=1.81 microM.

PMID- 17442461
TI  - [The contribution of computed tomography coronary angiography in Kawasaki disease
      in adult patients. Report of two cases].
AB  - OBJECTIVES: During the past few years, multislice computed tomography coronary
      angiography has made great progress in terms of spatial and temporal resolution.
      Results on detection and quantification of stenoses are excellent. We found
      interesting reporting its achievements in aneurismal coronaropathies such as the
      Kawasaki disease. METHODS: We searched for young adults with Kawasaki disease who
      had a multislice computed tomography coronary angiography available. Several
      hospitals in the Paris area have been contacted and only two observations have
      been kept. RESULTS: Computed tomography provided higher performance than
      coronarography for the measurement of the real diameter of an aneurism taking
      into account the mural thrombus, evaluation of its links with the collateral
      branches and the other aneurisms, assessment of the development of recanalized
      vessels and the degree of development of collateral vessels, and visualization of
      non-circulating aneurisms which were not detected with coronary angiography. In
      addition, the evaluation of the location and the degree of the stenoses by the
      computed tomography matched the coronary angiography data. It was not possible to
      conclude with this observations that the computed tomography is better for the
      diagnostic of Kawasaki disease. CONCLUSION: Multislice computed tomography
      coronary angiography will be likely more and more used to detect and follow
      coronary anomalies in case of Kawasaki disease among teenagers and young adults.
      It is recommended for monitoring medium or large aneurisms in order to evaluate
      their progression to stenosis.

PMID- 17442462
TI  - [Syndrome of inappropriate antidiuretic hormone secretion disclosing a sinonasal
      neuroendocrine carcinoma: case report].
AB  - We report a 74-year-old woman with histologically confirmed neuroendocrine
      carcinoma of the nasal cavity disclosing a syndrome of inappropriate antidiuretic
      hormone secretion (SIADH). Since SIADH is a paraneoplastic syndrome commonly
      associated with small cell lung cancer, an extra-pulmonary localisation of
      neuroendocrine carcinoma has to be investigated.

PMID- 17442463
TI  - Continuous infusion of methylprednisolone via paediatric parenteral nutrition: a
      pharmacokinetic animal study.
AB  - BACKGROUND & AIMS: The aim of our study consisted to measure the pharmacokinetic
      parameters of methylprednisolone administered in a continuous infusion of a
      paediatric parenteral nutrition mixture for 24h in the rabbit. METHODS: Fourteen
      rabbits were split into two groups and assigned a different administration
      vehicle (all-in-one or two-in-one nutrition mixture). We used USC PACK*
      pharmacokinetics software to compare the influence of the composition of the
      paediatric parenteral nutritional solutions on the values of the pharmacokinetic
      parameters of methylprednisolone. RESULTS: Neither the steady-state plasma
      concentrations of methylprednisolone hemisuccinate nor the values of the
      pharmacokinetic parameters of methylprednisolone differed significantly when
      administered in two-in-one or all-in-one nutrition mixtures. CONCLUSIONS: The
      composition of the nutritional medium had no discernable effect on the
      bioavailability of methylprednisolone. Neither the speed at which the steady
      state plasma concentration was reached, nor the values of the pharmacokinetic
      parameters of methylprednisolone were significantly modified.

PMID- 17442464
TI  - A nutritional support team in the pediatric intensive care unit: changes and
      factors impeding appropriate nutrition.
AB  - BACKGROUND & AIMS: The aims of this study were to determine the impact of a
      nutritional support team (NST) intervention in a pediatric intensive care unit
      (PICU) and to identify the factors at admission that were associated to a delay
      to achieve a sustained optimal caloric intake (SOCI). METHODS: Caloric and
      protein intake and nutritional parameters were compared in 82 children in 2000
      and 2003, respectively before and after the introduction of a NST. Predictive
      factors of a delay to achieve the SOCI were identified using multivariate
      analysis. RESULTS: There was no difference in 2000 and 2003, respectively,
      regarding cumulative caloric deficits (19+/-15.7 vs. 20.7+/-14.8 kcal/kg day),
      cumulative protein deficits (0.26+/-0.31 vs. 0.22+/-0.20 g/kg day), time to
      achieve a SOCI (7 vs. 7 days). Factors at admission associated with a delay to
      achieve a SOCI were a pediatric risk of mortality (PRISM) score > 10 (hazard
      ratio 0.58; 95% CI 0.44-0.77), a CRP > 50 mg/L (hazard ratio 0.49; 95% CI 0.35
      0.70), a fluid restriction (hazard ratio 0.51; 95% CI 0.37-0.71), and a weight
      for age > 3rd centile (hazard ratio 0.54; 95% CI 0.41-0.72). CONCLUSIONS: The
      intervention of a NST has not modified significantly the nutritional management.
      In pediatric intensive care, many factors identified at admission are associated
      with impairing appropriate nutrition.

PMID- 17442465
TI  - A recombinant subunit vaccine based on the insertion of 27 amino acids from Omp31
      to the N-terminus of BLS induced a similar degree of protection against B. ovis
      than Rev.1 vaccination.
AB  - The development of an effective subunit vaccine against brucellosis is a research
      area of intense interest. The enzyme lumazine synthase from Brucella spp. (BLS)
      is highly immunogenic, presumably due to its decameric arrangement and remarkable
      stability. In this work we decided to develop a chimera with the scaffold protein
      BLS decorated with 10 copies of a known protective epitope derived from an outer
      membrane protein of 31kDa (Omp31) from Brucella spp. Vaccination of BALB/c mice
      with the chimera as a recombinant protein (rBLSOmp31) provided the best
      protection level against Brucella ovis, which was higher than the given by the co
      delivery of both recombinant proteins (rBLS + rOmp31) and similar than the
      control vaccine Brucella melitensis strain Rev.1. Moreover rBLSOmp31 induced
      protection against Brucella melitensis but to a lesser degree than Rev.1. The
      chimera induced a strong humoral response against the inserted peptide. It also
      induced peptide- and BLS-specific T helper 1 and cytotoxic T responses. In
      conclusion, our results indicate that BLSOmp31 could be a useful candidate for
      the development of subunit vaccines against brucellosis since it elicits humoral,
      T helper and cytotoxic immune responses and protection against smooth and rough
      species of Brucella.

PMID- 17442466
TI  - Phase I dose escalation safety and immunogenicity trial of Plasmodium falciparum
      apical membrane protein (AMA-1) FMP2.1, adjuvanted with AS02A, in malaria-naive
      adults at the Walter Reed Army Institute of Research.
AB  - We report the first safety and immunogenicity trial of the Plasmodium falciparum
      vaccine candidate FMP2.1/AS02A, a recombinant E. coli-expressed protein based
      upon the apical membrane antigen-1 (AMA-1) of the 3D7 clone formulated with the
      AS02A adjuvant. We conducted an open-label, staggered-start, dose-escalating
      Phase I trial in 23 malaria-naive volunteers who received 8, 20 or 40microg of
      FMP2.1 in a fixed volume of 0.5mL of AS02A on a 0, 1, and 2 month schedule.
      Nineteen of 23 volunteers received all three scheduled immunizations. The most
      frequent solicited local and systemic adverse events associated with immunization
      were injection site pain (68%) and headache (29%). There were no significant
      laboratory abnormalities or vaccine-related serious adverse events. All
      volunteers seroconverted after second immunization as determined by ELISA. Immune
      sera recognized sporozoites and merozoites by immunofluorescence assay (IFA), and
      exhibited both growth inhibition and processing inhibition activity against
      homologous (3D7) asexual stage parasites. Post-immunization, peripheral blood
      mononuculear cells exhibited FMP2.1-specific lymphoproliferation and IFN-gamma
      and IL-5 ELISPOT assay responses. This is the first PfAMA-1-based vaccine shown
      to elicit both potent humoral and cellular immunity in humans. Encouraged by the
      potential of FMP1/AS02A to target host immunity against PfAMA-1 that is known to
      be expressed by sporozoite, hepatic and erythrocytic stages, we have initiated
      field trials of FMP2.1/AS02A in an endemic population in the Republic of Mali.

PMID- 17442467
TI  - Immunogenicity and reactogenicity of 23-valent pneumococcal polysaccharide
      vaccine among pregnant Filipino women and placental transfer of antibodies.
AB  - This randomized, controlled study among pregnant women evaluated the
      prevaccination distribution of anti-pneumococcal (Pnc) antibodies (Ab), the
      immunogenicity and reactogenicity of Pnc polysaccharide vaccine, and
      transplacental transfer of Ab. The Pnc vaccine group (N=106) received Pnc PS
      vaccine, Hemophilus influenzae type b conjugate vaccine and tetanus toxoid; the
      control group (N=54) received tetanus toxoid only. Sera and cord blood were
      assayed for anti-pnc Ab using enzyme immunoassay. In the Pnc vaccine group, anti
      Pnc Ab rose by 3- to 9-fold and was significantly higher in cord blood. In
      evaluating Pnc conjugate vaccines, the concentration of 0.35 microg/ml is
      suggested as the protective threshold against invasive disease. Around 90% of
      mothers had this level pre-vaccination. Considering the decay of passively
      acquired Ab and the growth of the infant, an Ab level in cord blood of at least
      4.4 microg/ml is needed if infants are to be protected up to 4 months of age.
      Cord blood anti-Pnc Ab was above this level in 60% and 10% of the Pnc vaccine and
      control groups, respectively. Maternal immunization with Pnc polysaccharide
      vaccine can provide prolonged protection through passively acquired Ab.

PMID- 17442468
TI  - Uptake and depuration of 131I from labelled diatoms (Skeletonema costatum) to the
      edible periwinkle (Littorina littorea).
AB  - Uptake and depuration of (131)I into winkles through consumption of the diatom
      Skeletonema costatum is described. The work follows on from previous studies that
      investigated the uptake of iodine into winkles from seawater and seaweed.
      Incorporation of (131)I in S. costatum from labelled seawater followed linear
      first-order kinetics with an uptake half-time of 0.40 days. Iodine uptake in
      winkles from labelled S. costatum also followed linear first-order kinetics, with
      a calculated equilibrium concentration (C(infinity)) of 42Bqkg(-1) and a transfer
      factor (TF) of 1.1x10(-4) with respect to labelled diatom food. This TF is lower
      than that observed for uptake of (131)I in winkles from labelled seaweed. For the
      depuration stage, a biphasic sequence with biological half-lives of 1.3 and 255
      days was determined. The first phase is biokinetically important, given that
      winkles can lose two-thirds of their activity during that period. This study
      shows that, whilst winkles can obtain radioactive iodine from phytoplankton
      consumption, they do not retain the majority of that activity for very long.
      Hence, compared with other exposure pathways, such as uptake from seawater and
      macroalgae, incorporation from phytoplankton is a relatively minor exposure
      route.

PMID- 17442469
TI  - Leaf extracellular ascorbate in relation to O(3) tolerance of two soybean
      cultivars.
AB  - Soybean [Glycine max (L.) Merr.] cultivars Essex and Forrest that exhibit
      differences in ozone (O(3)) sensitivity were used in greenhouse experiments to
      investigate the role of leaf extracellular antioxidants in O(3) injury responses.
      Charcoal-filtered air and elevated O(3) conditions were used to assess genetic,
      leaf age, and O(3) effects. In both cultivars, the extracellular ascorbate pool
      consisted of 80-98% dehydroascorbic acid, the oxidized form of ascorbic acid (AA)
      that is not an antioxidant. For all combinations of genotype and O(3) treatments,
      extracellular AA levels were low (1-30nmolg(-1) FW) and represented 3-30% of the
      total antioxidant capacity. Total extracellular antioxidant capacity was twofold
      greater in Essex compared with Forrest, consistent with greater O(3) tolerance of
      Essex. The results suggest that extracellular antioxidant metabolites in addition
      to ascorbate contribute to detoxification of O(3) in soybean leaves and possibly
      affect plant sensitivity to O(3) injury.

PMID- 17442470
TI  - The impact of sewage irrigation on the uptake of mercury in corn plants (Zea
      mays) from suburban Beijing.
AB  - The impact of sewage irrigation on the uptake and translocation of mercury (Hg)
      in corn plants (Zea mays) was investigated. Corn plants were harvested the same
      day from two nearby fields in suburban Beijing, one irrigated historically with
      sewage effluent, and one irrigated solely with groundwater. Hg content was
      analyzed in the soil, roots and stems, while percent moisture and soil organic
      content were analyzed in the soil samples. The concentration of Hg in the soil
      and roots, and the soil organic content were not significantly different between
      the two fields, despite the historic practice of sewage irrigation. Hg content in
      roots was positively correlated with soil Hg concentration (r=0.95, n=6). The
      transfer coefficients between roots and stems were significantly higher in the
      control site (control: 2.06, sewage-irrigated: 0.44, p<0.05), indicating that the
      barrier effect of the roots was not consistent between the two fields.

PMID- 17442471
TI  - Emerging health disparities in Botswana: examining the situation of orphans
      during the AIDS epidemic.
AB  - Botswana has the second highest HIV prevalence rate and highest rate of
      orphanhood in the world. Although child mortality rates have doubled in 15 years,
      the extent to which health disparities are connected to orphan status remains
      unclear. We conducted an analysis of the 2000 Botswana Multiple Indicator Cluster
      Survey to examine whether orphan-based health disparities exist. We measured
      health inequalities using anthropometric data among 2723 under-five year olds,
      nested in 1854 households, and 208 communities. We calculated multilevel logistic
      regression models to estimate the child, household, and regional determinants of
      growth failure. We found that orphaned children aged 0-4 are 49% more likely to
      be underweight than nonorphans (p<0.05) controlling for household poverty and
      other factors; and orphans disproportionately live in the poorest households.
      Throughout sub-Saharan Africa (SSA), Botswana is a leader in responding to the
      AIDS epidemic, in particular as one of the first countries to offer universal
      antiretroviral treatment. However, orphan-based health disparities confirm that
      the orphan response is still insufficient. Better data are needed to fully
      understand the mechanisms that lead to these disparities, and the public sector
      needs an increased capacity to fully implement the policies and programs designed
      to meet the needs of orphans. Findings from this study have important
      implications for countries throughout SSA, and Southern Africa in particular,
      where the number of orphans has doubled to tripled over the past 15 years.

PMID- 17442472
TI  - Behavioral indicators of household decision-making and demand for sanitation and
      potential gains from social marketing in Ghana.
AB  - Household demand for improved sanitation in developing countries is an important
      social and behavioral process with implications for public health, sanitation
      policy and planning, and sanitation design and technology development. This paper
      develops a behavioral approach to assess household demand for improved sanitation
      in Ghana. Adoption decision stages of preference, intention, and choice to
      install a toilet in Ghana are defined, measured in a survey, and used to estimate
      sanitation demand, identify factors affecting demand at each stage, and classify
      households by adoption stage to identify targeted demand-stimulation strategies.
      Results from a representative national sample of 536 households indicate that of
      74% of households without any home sanitation, 31% have some likelihood of
      installing a toilet within the next year, but only 6% are very likely to do so;
      62% had not considered the idea. Motivating and constraining factors are compared
      at each adoption stage and strategies likely to increase toilet installation in
      Ghana discussed. The approach is useful for assessing behavioral indicators of
      sanitation demand in developing countries and suggesting where marketing
      approaches can and cannot work to accelerate adoption of household sanitation
      improvements.

PMID- 17442473
TI  - Buprenorphine substitution treatment in France: drug users' views of the doctor
      user relationship.
AB  - The French system for drug substitution, or maintenance treatment, established in
      1996, differs from the often strict conditions attached to methadone clinics in
      other countries. Because of the predominant role of general practitioners and the
      flexible prescription rules for Subutex in France, the relationship between the
      physician and the drug user becomes a central element in the treatment. This
      article deals with the expectations that these users have of the physician, and
      their perception of his or her attitude towards them. In order to identify
      possible reasons for the absence of treatment compliance and of Subutex misuse,
      it focuses on the users' assessment of the physician's response to the problems
      they report. This study, based on a diversified convenience sample of 28 persons
      (19 men, 9 women) in treatment, showed 4 patterns of relationships between
      physicians and users, which differed in their focus: (1) closely focused on the
      posology of the prescription; (2) compliance with the prescribed regimen is the
      main issue in a relationship dominated by the physician; (3) an alliance between
      the physician and the user who is acknowledged as a person, and (4) a
      instrumental solely on the part of the user, who comes to procure a free, legal
      drug from a doctor's office. In all four case types, users had difficulty
      reporting other drug use or intravenous Subutex injection within this
      relationship, in which the stigma attached to drug dependence seems to reappear.
      Moreover, the lack of clarity about the treatment objectives and the time frame
      of the consultation limits the users' ability to integrate the treatment into
      their lives and to commit themselves to it. The heterogeneity and fragility of
      the users' situations, and the treatment objectives require regular assessment
      during contact with the physician. This constant reappraisal of the situation
      with the physician should help to optimize the treatment and avoid the hiatus
      that can generate or continue "misuse."

PMID- 17442474
TI  - Norcantharidin preferentially induces apoptosis in human leukemic Jurkat cells
      without affecting viability of normal blood mononuclear cells.
AB  - Norcantharidin (NCTD) is known to have anti-cancer potentials. The aim of this
      study was to assess the apoptosis-inducing effect of NCTD on human leukemic
      Jurkat cells. We found that NCTD preferentially inhibited the growth of Jurkat
      cells in a dose- and time-dependent manner, but not the growth of normal blood
      mononuclear cells (MNC). Pretreatment with agonistic (CH-11) and antagonistic
      (ZB4) Fas antibodies on Jurkat cells showed that NCTD-induced apoptosis might not
      involve Fas-FasL signaling. Flow cytometric assay of Jurkat cells treated with
      NCTD showed a markedly increased sub-G1 DNA phase and cell cycle arrest at S
      phase. Western blot analysis of NCTD-treated cells showed increased expressions
      of cytochrome c, active caspase-9 and -3, and cleavage of poly(ADP-ribose)
      polymerase (PARP), but the expressions of Bcl-2, Bax and apoptosis-inducing
      factor were not increased. The transcription factor STAT1 was translocated from
      cytosol to nucleus. Pancaspase inhibitor z-VAD-FMK not only limited the level of
      sub-G1 phase, but also prevented the degradation of PARP in NCTD-treated cells.
      The NCTD-induced cell cycle arrest and apoptosis were mediated through the
      regulation of ataxia-telangiectasia mutated (ATM), rather than P63 protein. The
      conditioned medium produced from human MNC (NCTD-MNC-CM) increased the percentage
      of apoptotic cells and the expression of PARP cleavage in Jurkat cells. Protein
      array assay of NCTD-MNC-CM showed 32.4- and 6.2-folds increases in TNF-alpha and
      GM-CSF, respectively, and the expression of MCP-1, GRO, RANTES and IL-10 was
      decreased. We conclude that NCTD can induce apoptosis in human leukemic Jurkat
      cells via a caspase-dependent pathway without affecting the viability of normal
      MNC, and that the apoptosis-inducing effect of NCTD can also be achieved by
      soluble cytokines produced from peripheral MNC.

PMID- 17442475
TI  - Pyrogallol, ROS generator inhibits As4.1 juxtaglomerular cells via cell cycle
      arrest of G2 phase and apoptosis.
AB  - Pyrogallol as a catechin compound has been employed as an O(2)(*-) generator and
      often used to investigate the role of ROS in the biological system. Here, we
      investigated the in vitro effect of pyrogallol on cell growth, cell cycle and
      apoptosis in As4.1 juxtaglomerular cells. Dose-dependent inhibition of cell
      growth was observed with IC(50) of about 60 microM for 48 h using MTT assay.
      Pyrogallol (100 microM) did not alter intracellular H(2)O(2) level and catalase
      activity, but increased the intracellular O(2)(-) level and decreased SOD
      activity in As4.1 cells. DNA flow cytometric analysis indicated that 50 and 100
      microM pyrogallol significantly increased G2 phase cells as compared with those
      of pyrogallol-untreated cells. Also, pyrogallol induced apoptosis as evidenced by
      flow cytometric detection of sub-G1 DNA content, annexin V binding assay and DAPI
      staining. This apoptosis process was accompanied with the loss of mitochondrial
      transmembrane potential (DeltaPsi(m)), Bcl-2 decrease, caspase-3 activation and
      PARP cleavage. Pan caspase inhibitor (Z-VAD) could significantly rescue As4.1
      cells from pyrogallol-induced cell death. But, the inhibitors of caspase-3,
      caspase-8, and caspase-9 did not prevent apoptotic events in pyrogallol-treated
      As4.1 cells. Taken together, we have demonstrated that an ROS inducer, pyrogallol
      inhibits the growth of As4.1 JG cells via cell cycle arrest and apoptosis, and
      suggest that the compound exhibits an anti-proliferative efficacy on these cells.

PMID- 17442476
TI  - Cytotoxicity of lawsone and cytoprotective activity of antioxidants in catalase
      mutant Escherichia coli.
AB  - Lawsone is an active naphthoquinone derivative isolated from henna (Lawsonia
      inermis L.), a widely used hair dye. Previous study on the toxicity of lawsone
      remains unclear since the involvement of oxidative stress and the kind of ROS
      (reactive oxygen species) involved have not been fully resolved yet. This present
      study reports the cytotoxic effects of lawsone and henna. We carried out CAT
      assay (a zone of inhibition test of bacterial growth and colony-forming
      efficiency test of transformant Escherichia coli strains that express mammalian
      catalase gene derived from normal catalase mice (Cs(a)) and catalase-deficient
      mutant mice (Cs(b))), Ames mutagenicity assay and H(2)O(2) generation assay.
      Lawsone generated H(2)O(2) slightly in phosphate buffer system and was not
      mutagenic in Ames assay using TA 98, TA 100 and TA 102, both in the absence and
      presence of metabolic activation. Lawsone exposure inhibited the growth of both
      Cs(a) and Cs(b) strains in a dose-dependent manner. Mean zone diameter for Cs(a)
      was 9.75+/-0.96 mm and 12.75+/-1.5 mm for Cs(b). Natural henna leaves did not
      show toxic effects, whereas two out of four samples of marketed henna products
      were shown toxicity effects. Catalase abolished zone of inhibition (ZOI) of
      marketed henna products, eliminated ZOI of lawsone in a dose-dependent manner and
      low concentration of exogenous MnSOD and Cu/ZnSOD eliminated the toxicity.
      Histidine and DTPA, the metal chelator; BHA and low concentration of capsaicin,
      the inducer of NADH-quinone reductase, effectively protected Cs(a) and Cs(b)
      against lawsone in this study. We suggest that lawsone cytotoxicity is probably
      mediated, at least in part, by the release of O(2)(-), H(2)O(2) and OH(-).

PMID- 17442477
TI  - Effects of low-dose lipopolysaccharide (LPS) pretreatment on LPS-induced intra
      uterine fetal death and preterm labor.
AB  - Lipopolysaccharide (LPS) has been associated with adverse developmental outcome,
      including embryonic resorption, intra-uterine fetal death (IUFD), intra-uterine
      growth retardation (IUGR) and preterm delivery in rodents. The purpose of the
      present study was to investigate whether administration of a low-dose LPS to the
      pregnant mice induce a reduced sensitivity to subsequent high-dose LPS-induced
      IUFD and preterm labor. We found that LPS-induced IUFD was obviously attenuated
      when the pregnant mice were pretreated with low-dose LPS (10 microg/kg, i.p.) 24h
      before high-dose LPS (120 microg/kg, i.p.). Consistent with its protective
      effect, when administered 24h before high-dose LPS, low-dose LPS pretreatment
      obviously inhibited the releases of tumor necrosis factor alpha (TNF-alpha) in
      maternal serum and amniotic fluid and attenuated LPS-induced placental lipid
      peroxidation and GSH depletion. However, when administered 4h before high-dose
      LPS, low-dose LPS pretreatment did not induced a reduced sensitivity to
      subsequent high-dose LPS-induced release of TNF-alpha in maternal serum and
      amniotic fluid. Actually, low-dose LPS pretreatment 4h before high-dose LPS
      worsened LPS-induced oxidative stress in mouse placenta and increased nitric
      oxide production in maternal serum and amniotic fluid. Correspondingly, low-dose
      LPS pretreatment 4h before high-dose LPS aggravated LPS-induced IUFD. Taken
      together, these results indicate that whether a low-dose LPS exposure during
      pregnancy produce LPS hyporesponsiveness depends on the interval between the two
      doses of LPS. When administered 24h before high-dose LPS, a low-dose LPS
      pretreatment induces a reduced sensitivity to subsequent high-dose LPS-induced
      IUFD, TNF-alpha production and oxidative stress.

PMID- 17442478
TI  - Mitochondrial carrier family: repertoire and peculiarities of the cellular slime
      mould Dictyostelium discoideum.
AB  - Proteins of the mitochondrial carrier family (MCF) mediate the transport of a
      large range of compounds, including metabolites and cofactors. They are localized
      mainly in the inner mitochondrial membrane, except for a few members found in the
      membranes of peroxisomes. Similarity searches among Dictyostelium discoideum
      protein sequences identified a total of 31 MCF members. All these are membrane
      proteins that possess three characteristic repeats of a domain of approximately
      100 residues. Among them, three proteins have supplementary structural domains
      consisting of Ca(2+)-binding motifs made up of 2 or 4 EF-hand units localized on
      the N-terminal end, facing the mitochondrial intermembrane space. The nature of
      transported substrates is proposed on the basis of sequence comparison with
      orthologs characterized biochemically in other organisms, of phylogenetic
      analysis, and of the conservation of discriminating amino acid residues belonging
      to the substrate binding sites. Carriers have been grouped in subclasses based on
      their specificity for the transport of nucleotides, amino acids or keto acids.
      Furthermore, we have identified an iron carrier of the mitoferrin type, an
      inorganic phosphate carrier, and three carriers with similarity to uncoupler
      proteins. This study provides a focus for mitochondrial carrier analysis in
      Dictyostelium discoideum.

PMID- 17442479
TI  - Retention of CPR skills learned in a traditional AHA Heartsaver course versus 30
      min video self-training: a controlled randomized study.
AB  - BACKGROUND: Bystander CPR improves outcomes after out of hospital cardiac arrest.
      The length of current 4-h classes in cardiopulmonary resuscitation (CPR) is a
      barrier to more widespread dissemination of CPR training and older adults in
      particular are underrepresented in traditional classes. Training with a brief
      video self-instruction (VSI) program has shown that this type of training can
      produce short-term skill performance at least as good as that seen with
      traditional American Heart Association (AHA) Heartsaver training, although it is
      unclear whether there is comparable skill retention. METHODS AND RESULTS: Two
      hundred and eight-five adults between the ages of 40 and 70 who had no CPR
      training within the past 5 years were assigned at random to a no-training control
      group, Heartsaver (HS) training, or one of three versions of brief VSI (i.e.,
      self-trained-ST subjects). Post-training performance of CPR skills was assessed
      in a scenario format by human examiners and by sensored manikin at Time 1
      (immediately post-training) and again at Time 2 (2 months post-training).
      Performance by controls was assessed only once. Significant (P<.001) decline was
      observed in the three measures recorded by examiners; assess responsiveness (from
      72% to 60% for HS subjects and from 90% to 77% for ST subjects), call 911 (from
      82% to 74% for HS subjects and from 71% to 53% for ST subjects), and overall
      performance (from 42% to 30% for HS subjects and from 60% to 44% for ST
      subjects). Significant (P<.001) decline was observed in two of three skills
      measured by a sensored manikin: ventilation volume (from 40% to 36% for HS
      subjects and from 61% to 41% for ST subjects, with a significant [P=.028]
      interaction) and correct hand placement (from 68% to 59% for HS subjects and from
      80% to 64% for ST subjects). Heartsaver and self-trained subjects generally
      showed similar rates of decline. At Time 2, examiners rated trained subjects
      better than untrained controls in all skills except calling 911, where self
      trained subjects did not differ from controls; manikin data revealed that trained
      subjects' performance was better than that of controls for ventilation volume,
      but had declined to the level of controls for both hand placement and compression
      depth. CONCLUSIONS: Adults between 40 and 70 years of age who participated in a
      CPR VSI program experienced performance decline in their CPR skills after a post
      training interval of 2 months. However, this decline was no greater than that
      seen in subjects who took Heartsaver training. The VSI program produced retention
      performance at least as good as that seen with traditional training. Additional
      effort is needed to improve both initial performance and retention of CPR skills.
      CONDENSED ABSTRACT: Retention of CPR skills was compared 2 months post-training
      for adults between 40 and 70 years old who had taken either a traditional
      Heartsaver CPR course or a 22-min video self-directed training course. Although
      performance declines occurred in the 2-month interval, self-trained subjects
      generally demonstrated CPR skill retention equivalent to that of Heartsaver
      trained subjects, although for both groups skill decline on some measures reached
      the level of untrained controls.

PMID- 17442481
TI  - What do we really know about prostate cancer?

PMID- 17442480
TI  - Dimerization of VEGF receptors and implications for signal transduction: a
      computational study.
AB  - Vascular endothelial growth factor (VEGF) is a potent cytokine involved in the
      induction of neovascularization. Secreted as a cysteine-linked dimer, it has two
      binding sites at opposite poles through which it may bind VEGF receptors
      (VEGFRs), receptor tyrosine kinases found on the surface of endothelial and other
      cells. The binding of a VEGF molecule to two VEGFR molecules induces
      transphosphorylation of the intracellular domains of the receptors, leading to
      signal transduction. The dominant mechanism of receptor dimerization is not
      clear: the receptors may be present in an inactive pre-dimerized form, VEGF
      binding first to one of the receptors, the second receptor then ideally located
      for dimerization; or VEGF may bind receptor monomers on the cell surface, which
      then diffuse and bind to available unligated receptor monomers to complete the
      activation. Both processes take place and one or other may dominate on different
      cell types. We demonstrate the impact of dimerization mechanism on the binding of
      VEGF to the cell surface and on the formation of active signaling receptor
      complexes. We describe two methods to determine which process dominates, based on
      binding and phosphorylation assays. The presence of two VEGF receptor
      populations, VEGFR1 and VEGFR2, can result in receptor heterodimer formation. Our
      simulations predict that heterodimers will comprise 10-50% of the active,
      signaling VEGF receptor complexes, and that heterodimers will form at the expense
      of homodimers of VEGFR1 when VEGFR2 populations are larger. These results have
      significant implications for VEGF signal transduction and interpretation of
      experimental studies. These results may be applicable to other ligand-receptor
      pairs, in particular PDGF.

PMID- 17442482
TI  - Dysadherin: a new player in cancer progression.
AB  - Dysadherin is a cancer-associated cell membrane glycoprotein that promotes
      experimental cancer metastasis. Here we review recent work that has provided
      insights into possible mechanisms of action of this newly recognized player in
      the cancer progression process. Dysadherin modulates cell phenotype in a number
      of ways, including down-regulation of E-cadherin-mediated cell adhesion, and up
      regulation of chemokine production. In this way, expression of dysadherin in a
      tumor can influence both the tumor cell itself and the stromal compartment, so as
      to create conditions that are more permissive for metastatic spread. Dysadherin
      expression is also an independent prognostic indicator of metastasis and survival
      for many different types of human cancer. Thus, dysadherin may represent a new
      molecular target for the visualization, prevention or treatment of advanced
      cancer.

PMID- 17442483
TI  - AKAP12 induces apoptotic cell death in human fibrosarcoma cells by regulating
      CDKI-cyclin D1 and caspase-3 activity.
AB  - AKAP12 (A-Kinase anchoring protein 12) is a protein kinase C substrate and a
      potential tumor suppressor. AKAP12 is down-regulated by several oncogenes and
      strongly suppressed in various cancers including prostate, ovarian and breast
      cancers. AKAP12 acts as a regulator of mitogenesis by anchoring key signal
      proteins such as PKA, PKC, and cyclins. In this study, AKAP12 was found to
      suppress tumor cell viability by inducing apoptosis via caspase-3 in HT1080
      cells. This AKAP12-induced apoptosis was associated with a decreased expression
      of Bcl-2 and increased expression of Bax. Moreover, AKAP12-transfectant strongly
      induced the expression of Cip1/p21 and Kip1/p27, but resulted in a decrease in
      cyclin D1 involved in G(1) progression. Accordingly, these results suggest that
      AKAP12 may play an important role in tumor growth suppression by inducing
      apoptosis with the regulation of multiple molecules in the cell cycle
      progression.

PMID- 17442484
TI  - Absence of lymphangiogenesis in ductal breast cancer at the primary tumor site.
AB  - Solid evidence for a relationship between lymphangiogenesis and prognosis in
      human breast cancer is still lacking. Evidence for ongoing lymphangiogenesis in
      breast cancer is only provided by animal studies. In the present study we
      investigated lymphatic vessel density as well as the expression level of the
      lymphangiogenic factors VEGF-C and -D in a series of 121 ductal breast cancer
      tissues using immunohistochemical stainings. We found that in the primary tumors
      the lymphatic vessel density, as well as the expression of both VEGF-C and -D,
      did not relate to grade, tumor stage, progression or patient survival.
      Furthermore, in tumors in which lymphatic vessels were present, a Ki
      67/podoplanin double staining indicated the absence of proliferating lymphatic
      endothelial cells. In contrast, we did find a correlation between intratumoral
      lymphatic vessel density inside the lymph node metastases and patient survival.
      Another parameter that revealed prognostic value was the presence of tumor cells
      within the lymphatic vessels. This parameter did predict survival in patients
      with an age below 63 only. Interestingly, expression of VEGF-D was found to be
      related to the presence of intralymphatic tumor cells.

PMID- 17442485
TI  - The effect of functional groups on oligomerization of phenolics on activated
      carbon.
AB  - Adsorption of seven phenolic compounds, namely phenol, 2-methylphenol, 2
      ethylphenol, 2-chlorophenol, 2-nitrophenol, 4-chlorophenol, and 4-nitrophenol on
      granular activated carbon (GAC) F400 and two activated carbon fibers (ACFs), ACC
      10 and ACC-15 were conducted to study the impact of functional groups on
      oligomerization. Single solute adsorption and binary solute adsorption were
      conducted under anoxic (absence of molecular oxygen) and oxic (presence of
      molecular oxygen) conditions at 23+/-1 degrees C. For F400, the critical
      oxidation potential (COP), influenced by substitution of functional group, was
      found to be a limiting factor in oligomerization of adsorbates. For ACC-10, which
      has narrow pore size distribution (PSD) and small critical pore diameter (8.0A),
      only phenol and 2-methylphenol showed occurrence of oligomerization under oxic
      conditions. The degree of oligomerization under oxic conditions was related to
      the PSD of the adsorbent. The micro-pore diameter of the ACFs effectively reduced
      the oligomerization process. The oxic and anoxic binary adsorption isotherms of
      phenol/2-ethylphenol and 2-methylphenol/2-nitrophenol on ACC-10 overlapped
      indicating hampering of oligomerization by the limited micro-pore diameter of
      ACFs. The Ideal Adsorbed Solution Theory (IAST), using the Myers equation for
      correlating the single-solute anoxic isotherms, well predicted both anoxic and
      oxic binary isotherms.

PMID- 17442486
TI  - Role of tissue transglutaminase type 2 in calbindin-D28k interaction with ataxin
      1.
AB  - Spinocerebellar ataxia-1 (SCA1) is caused by the expansion of a polyglutamine
      repeats within the disease protein, ataxin-1. The mutant ataxin-1 precipitates as
      large intranuclear aggregates in the affected neurons. These aggregates may
      protect neurons from mutant protein and/or trigger neuronal degeneration by
      encouraging recruitment of other essential proteins. Our previous studies have
      shown that calcium binding protein calbindin-D28k (CaB) associated with SCAl
      pathogenesis is recruited to ataxin-l aggregates in Purkinje cells of SCAl mice.
      Since our recent findings suggest that tissue transglutaminase 2 (TG2) may be
      involved in crosslinking and aggregation of ataxin-l, the present study was
      initiated to determine if TG2 has any role in CaB-ataxin-l interaction. The
      guinea pig TG2 covalently crosslinked purified rat brain CaB. Time dependent
      progressive increase in aggregation produced large multimers, which stayed on top
      of the gel. CaB interaction with ataxin-l was studied using HeLa cell lysates
      expressing GFP and GFP tagged ataxin-l with normal and expanded polyglutamine
      repeats (Q2, Q30 and Q82). The reaction products were analyzed by Western blots
      using anti-polyglutamine, CaB or GFP antibodies. CaB interacted with ataxin-1
      independent of TG2 as the protein-protein crosslinker DSS stabilized CaB-ataxin-l
      complex. TG2 crosslinked CaB preferentially with Q82 ataxin-1. The crosslinking
      was inhibited with EGTA or TG2 inhibitor cystamine. The present data indicate
      that CaB may be a TG2 substrate. In addition, aggregates of mutant ataxin-l may
      recruit CaB via TG2 mediated covalent crosslinking, further supporting the
      argument that ataxin-l aggregates may be toxic to neurons.

PMID- 17442488
TI  - An association study between cathechol-O-methyltransferase gene and mental
      retardation in the Chinese Han population.
AB  - Cathechol-O-methyltransferase (COMT) regulates the amount of dopamine in the
      prefrontal cortex (PFC). Substantial studies indicate a close relationship
      between COMT and several human psychotic disorders. The case-control method was
      used to study the association between mental retardation (MR) and genetic
      variants of COMT. Three single nucleotide polymorphisms (SNPs: rs4680, rs165656
      and rs165774), in the cathechol-O-methyltransferase (COMT) gene, were genotyped
      by PCR-RFLP method. Individual SNP analysis shows significant differences only at
      SNP rs165656 for both genotype and allele frequency when comparing MR cases and
      controls (p=0.023, 0.011, respectively). Further haplotype analysis indicates
      that there are two haplotype sets, rs165656-rs4680 and rs165656-rs165774, which
      show statistical differences between MR cases and controls (global p=0.047,
      p=0.033, respectively). Our results suggest a positive association between the
      genetic variants of the COMT gene and MR in the Chinese Han population in the
      Qinba region.

PMID- 17442487
TI  - Characteristic of hypothalamic kisspeptin expression in the pubertal development
      of precocious female rats.
AB  - To investigate the potential role of kisspeptin in the advance onset of puberty
      in precocious puberty, model rats induced by danazol were used to study the
      developmental expression of hypothalamic kisspeptin. Kisspeptin immunoreactive
      cells were observed in the arcuate nucleus (ARC), periventricular nucleus (PeN)
      and preoptic area (POA) in model rats on the day of onset-puberty. On the day of
      post-puberty, however, the number of kisspeptin immunoreactive cells in ARC and
      PeN decreased while the number of those cells in POA increased. Kisspeptin
      immunoreactive cells were not detected in hypothalamus in both normal and model
      rats at their pre-puberty stages. Furthermore, the expression of hypothalamic
      Kiss-1 mRNA reached top on the day of onset-puberty in both of the normal and
      model rats, and the expression of Kiss-1 mRNA increased significantly in the
      model rats compared with those in the normal ones. Our results indicated that
      kisspeptin might involve in the advance onset of puberty in danazol induced
      female precocious model rats.

PMID- 17442489
TI  - Serum levels of brain-derived neurotrophic factor in patients with schizophrenia
      and bipolar disorder.
AB  - There is evidence that major psychiatric discords such as schizophrenia (SZ) and
      bipolar disorder (BD) are associated with dysregulation of synaptic plasticity
      with downstream alterations of neurotrophins. Brain-derived neurotrophic factor
      (BDNF) is the most widely distributed neurotrophin in the central nervous system
      (CNS), and performs many biological functions such as promoting the survival,
      differentiation, and plasticity of neurons. Variants in the BDNF gene increase
      the risk of SZ and bipolar disorder. Chronic administration of drugs used to
      treat SZ and BD, such as lithium, valproate, quetiapine, clozapine, and
      olanzapine, increases BDNF expression in rat brain. To examine serum BDNF, three
      groups of chronically medicated DSM-IV SZ patients, on treatment with clozapine
      (n=27), typical (n=14), and other atypical antipsychotics (n=19), 30 euthymic BD
      patients, and 26 healthy control had 5 ml blood samples collected by
      venipuncture. Serum BDNF levels were significantly higher in SZ patients
      (p<0.001) when compared to either controls or euthymic BD patients. Increased
      BDNF in SZ patients might be related to the course of illness or to treatment
      variables. Prospective studies are warranted.

PMID- 17442491
TI  - Prevalence of Toxoplasma gondii in dogs from Sri Lanka and genetic
      characterization of the parasite isolates.
AB  - The prevalence of Toxoplasma gondii in 86 street dogs from Sri Lanka was
      determined. Antibodies to T. gondii were assayed by the modified agglutination
      test (MAT) and found in 58 (67.4%) of 86 dogs with titers of 1:20 in eight, 1:40
      in four, 1:80 in 10, 1:160 in 22, 1:320 in six, 1:640 in five, and 1:1280 or
      higher in three. Hearts, tongues, and brains (either separately or pooled) of 50
      dogs with MAT titers of 1:40 were selected for isolation of T. gondii by
      bioassays in mice. For bioassays, canine tissues were digested in pepsin and
      homogenates were inoculated subcutaneously into mice; the mice receiving canine
      tissues were examined for T. gondii infection. In all, T. gondii was isolated
      from 23 dogs. Interestingly, dog organs varied in their capacity to induce T.
      gondii infection in mice, muscles producing more positive results than the brain.
      The T. gondii isolates obtained from 23 seropositive dogs were PCR-RFLP genotyped
      using polymorphisms at 10 nuclear markers including SAG1, SAG2, SAG3, BTUB, GRA6,
      c22-8, c29-2, L358, PK1, a new SAG2, and an apicoplast marker Apico. Mixed
      infection with two genotypes was observed in one dog. Four genotypes were
      revealed, including three unique genotypes in addition to one belonging to the
      predominant Type III lineage. The 24 isolates were designated as TgDgSl 1-24.

PMID- 17442490
TI  - Inhibition by the chromaffin cell-derived peptide serine-histogranin in the rat's
      dorsal horn.
AB  - The heptadecapeptide histogranin, synthesized by adrenal chromaffin cells, is
      implicated in the analgesia produced by transplanting chromaffin cells into the
      spinal cord, including block of hyperalgesia mediated by NMDA-subtype glutamate
      receptors. To examine the neurophysiological basis for this analgesia, we applied
      the stable analog [Ser(1)]-histogranin (SHG) by iontophoresis near
      extracellularly recorded wide-dynamic range (WDR) neurons in anesthetized rats.
      When SHG was applied during peripheral electrical stimulation of A and C fibers
      at 0.1Hz, the C-fiber response was significantly inhibited but the A-fiber
      response was unaffected. SHG also opposed the NMDA-receptor-dependent post
      tetanic facilitation (wind-up) of C-fiber responses produced by increasing the
      rate of peripheral afferent stimulation to 1Hz for 20s. To test whether block of
      NMDA-subtype receptors could be wholly or partially responsible for this
      suppression, SHG was applied during sequential pulsed iontophoresis of three
      agonists targeting distinct excitatory synaptic receptors: NMDA, kainate and
      substance P. All three excitatory effects were reversed by SHG; this reversal
      outlasted the 10-30min observation period when higher SHG doses were applied
      (>60nA). Histogranin therefore probably produces prolonged spinal analgesia by
      opposing the basal and potentiating synaptic effects of C-fibers on dorsal horn
      neurons. Actions besides or in addition to NMDA-receptor antagonism (e.g.,
      agonism at inhibitory postsynaptic receptors or block of voltage-gated cation
      channels on C-fibers) are implied by the diversity of excitatory transmitters
      opposed by SHG.

PMID- 17442492
TI  - Genetic characterization of Toxoplasma gondii isolates in dogs from Vietnam
      suggests their South American origin.
AB  - Dogs are considered a potential risk for transmission of Toxoplasma gondii to
      humans because they can mechanically transmit oocysts to people and in certain
      parts of the world dog meat is consumed by humans. The prevalence of T. gondii in
      42 dogs from rural Vietnam was determined. Antibodies to T. gondii were assayed
      by the modified agglutination test, and found in 21 (50%) of 42 dogs with titers
      of 1:20 in six, 1:40 in seven, 1:80 in two, 1:160 in two, 1:320 in two, 1:640 in
      one, and 1:1280 or higher in one. Hearts, tongues and brains of 21 seropositive
      dogs were bioassayed in cats, mice or both. Tissues from eight seropositive dogs
      were fed to eight T. gondii-free cats. Feces of cats were examined for oocysts.
      T. gondii was isolated from eight dogs by bioassay in cats. Genotyping of these
      eight T. gondii isolates using polymorphisms at 10 nuclear markers including
      SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and a new SAG2, and an
      apicoplast marker Apico revealed two genotypes. Both genotypes were previously
      identified from the dog isolates in Colombia, suggesting their South America
      origin. However, they are different from the predominant Type I, II and III
      lineages that are widely spread in North America and Europe. This is the first
      report of isolation of viable T. gondii from any host in Vietnam.

PMID- 17442493
TI  - Experimental infection of domestic cats (Felis domesticus) with Cytauxzoon manul
      from Pallas' cats (Otocolobus manul).
AB  - In a random, blind study, six domestic cats were assigned to two treatment groups
      that received either sterile water or dexamethasone by subcutaneous injection
      prior to intravenous inoculation with Pallas' cat (Otocolobus manul) blood
      infected with Cytauxzoon manul. A seventh domestic cat served as a control and
      was inoculated only with sterile water. Cats were monitored for clinical signs
      consistent with cytauxzoonosis, and periodically screened for hemoparasitemia.
      All domestic cats (6/6) that received Pallas' cat blood infected with C. manul
      developed a low but detectible parasitemia by 9 days post-inoculation, yet
      remained clinically healthy. All domestic cats (7/7) were subsequently challenged
      with Cytauxzoon felis and developed clinical signs typical of cytauxzoonosis
      within 5 days post-challenge. Affected animals were euthanized and cytauxzoonosis
      was confirmed by histopathology. While inoculation of domestic cats with Pallas'
      cat blood infected with C. manul induced a parasitemia, it did not cause disease
      or provide protection against challenge with C. felis. Further studies are
      warranted to determine the potential for interspecies transmission and disease
      with C. manul.

PMID- 17442494
TI  - Linoleoyl lysophosphatidic acid and linoleoyl lysophosphatidylcholine are
      efficient substrates for mammalian lipoxygenases.
AB  - Oxygenation of two lysophospholipids, 1-linoleoyl lysophosphatidylcholine
      (linoleoyl-lysoPC) and 1-linoleoyl lysophosphatidic acid (linoleoyl-lysoPA), by
      reticulocyte lipoxygenase (LOX) or porcine leukocyte LOX was measured by
      monitoring the formation of conjugated dienes. Consistent with the above, the
      formation of linoleoyl-lysophospholipid hydroperoxide as oxygenation product was
      confirmed by LC/MS analyses. In further study, the oxygenation products of
      linoleoyl-lysoPC or linoleoyl-lysoPA were found to contain hydroperoxide group
      predominantly at C-13 with the S enantiomer as a major one, in a good agreement
      with the positional-specificity and stereo-selectivity of reticulocyte LOX or
      leukocyte LOX in oxygenation of linoleic acid. The kinetic study indicates that
      linoleoyl-lysoPA and linoleoyl-lysoPC are no less efficient than linoleic acid as
      substrates of reticulocyte LOX as well as leukocyte LOX. In contrast, these
      lysophospholipids were not oxygenated efficiently by potato LOX. Thus, linoleoyl
      lysophospholipids such as linoleoyl-lysoPA or linoleoyl-lysoPC could be utilized
      as efficient substrates for some mammalian lipoxygenases.

PMID- 17442495
TI  - Protective role of unconjugated bilirubin on complement-mediated hepatocytolysis.
AB  - Hyperbilirubinemia and complement-mediated immune attack on hepatocyte membrane
      are common features of certain hepatic diseases. To assess whether unconjugated
      bilirubin (UB) counteracts complement-mediated hepatocytolysis, we first
      generated a rabbit polyclonal antibody (Ab) against rat hepatocyte plasma
      membrane (RHPM). An assay performed with isolated rat hepatocytes in the presence
      of the polyclonal Ab and rat serum as complement donor demonstrated that UB
      inhibits cell lysis, as lactate dehydrogenase release into the medium was
      inhibited by the pigment in a dose-dependent manner. Immunofluorescence
      microscopy studies showed that UB significantly attenuates the binding of C3 to
      the hepatocyte-Ab complex. Further enzyme immunoassay studies showed that UB
      interferes the binding of C1q to purified anti-RHPM IgG, also in a dose-dependent
      manner. A dot-blot assay showed that [14C]-UB binds to C1q and human serum
      albumin (HSA) to a similar extent. A differential spectrum analysis of UB in the
      presence of C1q further confirmed that the pigment interacts with this protein.
      In conclusion, we demonstrated an inhibitory action of UB on complement-mediated
      Ab-induced hepatocytolysis, this action being evidenced at pathophysiological
      pigment concentrations (171 microM and higher). A direct binding of the pigment
      to C1q is likely involved.

PMID- 17442496
TI  - Modulations of the calcineurin/NF-AT pathway in skeletal muscle atrophy.
AB  - Calcineurin has been proposed to regulate skeletal muscle hypertrophy, while its
      relevance to the pathogenesis of muscle atrophy is unknown. The present study was
      aimed to investigate if perturbations of the calcineurin pathway may be involved
      in causing skeletal muscle atrophy in two different experimental conditions:
      cancer cachexia (rats bearing the AH-130 hepatoma), and hyperglycemia (rats
      treated with streptozotocin). Calcineurin expression in the gastrocnemius was
      comparable between tumor hosts and controls. By contrast, besides unchanged
      calcineurin mRNA levels, those of protein were lower in diabetic animals than in
      controls. The DNA-binding activity of the transcription factors NF-AT and MEF-2
      was analysed as an indirect measure of calcineurin activity in vivo. The nuclear
      translocation of both factors was similar in tumor hosts and controls.
      Consistently with the reduced calcineurin protein levels, NF-AT DNA-binding
      activity significantly decreased in the gastrocnemius of diabetic rats compared
      to controls. Finally, muscle wasting correction afforded in the AH-130 hosts by
      pentoxifylline or interleukin-15 was not paralleled by changes of calcineurin
      mRNA levels, while treatment of diabetic animals with dehydroepiandrosterone
      partially prevented calcineurin down-regulation. These results suggest that
      modulations of calcineurin activity may be involved in the pathogenesis of muscle
      wasting in diabetes though not in cancer cachexia.

PMID- 17442497
TI  - Lipoprotein[a] and cancer: anti-neoplastic effect besides its cardiovascular
      potency.
AB  - While the death rate from cancer has substantially decreased over the past
      decade, the search for effective and tolerable therapies is a great challenge as
      yet. The evidence that malignant cells cannot grow to a clinically detectable
      tumor mass and spread in the absence of an adequate vascular support, has opened
      a new area of research towards the selective inhibition or even destruction of
      tumor vessels. Angiostatin and angiostatin-related proteins are a family of
      specific angiogenesis inhibitors produced by tumors from a family of naturally
      occurring proteins, which also includes plasminogen and lipoprotein[a]. The anti
      angiogenic activity of these proteins resides in cryptic and highly-repetitive
      molecular domains hidden within the protein moiety, called kringles.
      Lipoprotein[a] is an intriguing molecule consisting of a low-density lipoprotein
      core in addition to the covalently bound apolipoprotein[a]. Apolipoprotein[a] is
      characterized by an inactive protease domain, a single copy of the plasminogen
      kringle V and multiple repeats of domains homologous to the plasminogen kringle
      IV. Reliable studies on animal models indicate that the proteolytic break-down
      products of apolipoprotein[a] would posses anti-angiogenic and anti-tumoral
      properties both in vitro and in vivo, a premise to develop novel therapeutic
      modalities which may efficiently suppress tumor growth and metastasis. This
      review is focused on the biochemical structure, metabolism and the anti
      angiogenic activity of this unique and elusive kringle-containing lipoprotein.

PMID- 17442498
TI  - Sleep fragmentation elevates behavioral, electrographic and neurochemical
      measures of sleepiness.
AB  - Sleep fragmentation, a feature of sleep apnea as well as other sleep and
      medical/psychiatric disorders, is thought to lead to excessive daytime
      sleepiness. A rodent model of sleep fragmentation was developed (termed sleep
      interruption, SI), where rats were awakened every 2 min by the movement of an
      automated treadmill for either 6 or 24 h of exposure. The sleep pattern of rats
      exposed to 24 h of SI resembled sleep of the apneic patient in the following
      ways: sleep was fragmented (up to 30 awakening/h), total rapid eye movement (REM)
      sleep time was greatly reduced, non-rapid eye movement (NREM) sleep episode
      duration was reduced (from 2 min, 5 s baseline to 58 s during SI), whereas the
      total amount of NREM sleep time per 24 h approached basal levels. Both 6 and 24 h
      of SI made rats more sleepy, as indicated by a reduced latency to fall asleep
      upon SI termination. Electrographic measures in the recovery sleep period
      following either 6 or 24 h of SI also indicated an elevation of homeostatic sleep
      drive; specifically, the average NREM episode duration increased (e.g. for 24 h
      SI, from 2 min, 5 s baseline to 3 min, 19 s following SI), as did the NREM delta
      power during recovery sleep. Basal forebrain (BF) levels of extracellular
      adenosine (AD) were also measured with microdialysis sample collection and high
      performance liquid chromatography detection, as previous work suggests that
      increasing concentrations of BF AD are related to sleepiness. BF AD levels were
      significantly elevated during SI, peaking at 220% of baseline during 30 h of SI
      exposure. These combined findings imply an elevation of the homeostatic sleep
      drive following either 6 or 24 h of SI, and BF AD levels appear to correlate more
      with sleepiness than with the cumulative amount of prior wakefulness, since total
      NREM sleep time declined only slightly. SI may be partially responsible for the
      symptom of daytime sleepiness observed in a number of clinical disorders, and
      this may be mediated by mechanisms involving BF AD.

PMID- 17442499
TI  - Histochemical evidence for wide expression of the metalloendopeptidase nardilysin
      in human brain neurons.
AB  - Nardilysin is a metalloendopeptidase that in vitro cleaves peptides such as
      dynorphin-A, somatostatin-28, alpha-neoendorphin and glucagon at the N-terminus
      of arginine and lysine residues in dibasic moieties. The enzyme is highly
      expressed in many endocrine tissues. Nardilysin has also been found in the brain.
      Previously, we have detected that nardilysin interacts with brain-specific
      proteins, i.e. p42(IP4)/centaurin-alpha1 [Stricker R, Chow KM, Walther D, Hanck
      T, Hersh LB, Reiser G (2006) Interaction of the brain specific protein
      p42(IP4)/centaurin-alpha1 with the peptidase nardilysin is regulated by the
      cognate ligands of p42(IP4), PtdIns(3,4,5)P(3) and Ins(1,3,4,5)P(4), with
      stereospecificity. J Neurochem 98:343-354]. However, very little is known about
      the distribution of nardilysin in the brain. The aim of the present study was to
      reveal its regional distribution and cellular localization in developing and
      adult human brain. Using immunohistochemistry and Western blot analysis we
      demonstrate that the enzyme is widely, but unevenly, expressed in the human
      brain. We found high staining intensity in the hypothalamus, neocortex and brain
      stem nuclei. The cellular localization is almost exclusively confined to neurons.
      In pre- and perinatal human brain cortex, most neurons express the enzyme. In
      cortical neurons nardilysin protein was found to be partially co-localized with
      parvalbumin but not calretinin. No co-expression was seen with somatostatin-28
      immunoreactivity. A considerable overlap was revealed between p42(IP4) and
      nardilysin. Our data support the hypothesis that nardilysin might possibly play a
      role in brain development, whereas its putative function in brain peptide
      metabolism remains to be clarified further.

PMID- 17442500
TI  - Lithium, arginine vasopressin and the dex/CRH test in mood disordered patients.
AB  - The impact of lithium on arginine vasopressin (AVP) release has implications for
      our understanding of the pathophysiology and treatment of mood disorders and for
      the interpretation of neuroendocrine studies. In this secondary analysis of
      neuroendocrine, data from 23 patients with chronic major depressive disorder, 41
      patients with bipolar disorder and 18 healthy controls, we examine the
      relationship between lithium therapy, AVP levels and the cortisol response to the
      dexamethasone/corticotropin-releasing hormone (dex/CRH) test. These data
      demonstrate that patients taking lithium have elevated post-dexamethasone AVP
      levels compared to both healthy controls and patients not on lithium.

PMID- 17442501
TI  - Can low dose diagnostic dental radiation trigger Sjogren's syndrome?
AB  - Sjogren's syndrome (SS), first described by Swedish ophthalmologist Henrik
      Sjogren in 1930, is a chronic inflammatory, autoimmune disorder characterized by
      diminished lacrimal and salivary glands secretion resulting in
      keratoconjunctivitis sicca and xerostomia. One factor instrumental in severe
      salivary gland damage and salivary flow decrement is radiation therapy.
      Apoptosis, implicated in autoimmune diseases, has been shown to be responsible
      for this damage. However, there are no studies investigating the effect of
      diagnostic radiation (low dose) on salivary glands. A safe level of radiation has
      not been established thus far. Diagnostic radiation has been used from 1896, but
      generally applied only from 1916. Dr. Sjogren identified SS in 1930. It is
      possible that the introduction of X-rays for diagnostic purposes is associated
      with SS onset. Available data show drastically reduced use of diagnostic dental
      radiation in developing countries and a concomitantly drastically reduced or lack
      of SS in these countries. In countries like India with a population of 1.1
      billion (health care level II country), primary SS has been reported to be rare
      (total of 27 and 23 primary SS and secondary SS patients respectively reported
      thus far), while a health care level I country like USA, with a population of 300
      million, there are about 2-4 million SS patients. Health care level IV countries
      do not have a single reported case of SS. There is also evidence for ultraviolet
      radiation inducing subcutaneous lupus erythematosus, an autoimmune disorder. We
      hypothesize that diagnostic dental radiation could be a factor for the
      development of SS as a result of either radiation induced apoptosis or through
      oxidative modification of proteins.

PMID- 17442502
TI  - Establishment of an organotypic in vitro culture system and its relevance to the
      characterization of human prostate epithelial cancer cells and their stromal
      interactions.
AB  - Human prostatic adenocarcinoma fragments (1-6mm) were cultured on collagen
      sponges in medium supplemented or not supplemented with 4,5alpha-dihydrotesterone
      (DHT) until 3 weeks, maintaining the three-dimensional (3D) epithelial and
      stromal organization present in the tumor in vivo. With time, in the presence of
      DHT, locally progressive cribriform nests of neoplastic cells with proliferative
      rates higher than those inside the fragment developed on the surface, while the
      stroma became more dissociated, and fibrosis replaced the muscular component. The
      3D-culture provides a promising approach for studying the development and
      phenotype of prostate epithelial tumor progenitor cells and their stromal
      interactions.

PMID- 17442503
TI  - SQAB 2006: "It's the Non-Arbitrary Metrics, Stupid!".

PMID- 17442504
TI  - Patterns of internal gene duplication in the course of metazoan evolution.
AB  - Internal duplication can enhance the function of a gene or provide raw material
      for the emergence of a new function in a gene. Therefore, it is interesting to
      see whether the frequency of internal duplication has increased during metazoan
      evolution. The growing number of sequenced eukaryotic genomes provides an
      excellent opportunity to study the change in the pattern of internal duplication
      in the course of metazoan evolution. We studied repeated segments in proteins in
      the proteomes of 11 eukaryotes. We found that the frequency of internal
      duplication in Caenorhabditis elegans and Drosophila melanogaster (two
      protostomes) is higher than that in fungi but lower than that in chordates.
      Moreover, the frequencies of internal duplication for the chordates studied are
      largely similar. We classified orthologous proteins of chordates into three
      antiquity groups and found that more recently derived proteins in the metazoan
      lineage have higher repetitiveness than older ones. Our analysis suggests that
      lineage-specific internal duplication in protein evolution increases with
      organismal complexity before the emergence of chordates but not so afterward.
      Proteins with repeated regions might have been preferred before the protostome
      chordate split. This finding supports the suggestion that exon-shuffling occurred
      more frequently after the first multicellular organism appeared and might have
      contributed to the metazoan radiation.

PMID- 17442505
TI  - Regional FMRP deficits and large repeat expansions into the full mutation range
      in a new Fragile X premutation mouse model.
AB  - Carriers of FMR1 alleles with 55-200 repeats in the 5' UTR are at risk for
      Fragile X associated tremor and ataxia syndrome. The cause of the neuropathology
      is unknown but is thought to be RNA-mediated. Maternally transmitted premutation
      alleles are also at risk of expansion of the repeat tract into the "full
      mutation" range (>200 repeats). The mechanism responsible for expansion is
      unknown. Full mutation alleles produce reduced amounts of the FMR1 gene product,
      FMRP, which leads to Fragile X mental retardation syndrome. We have developed a
      murine model for Fragile X premutation carriers that recapitulates key features
      seen in humans including a direct relationship between repeat number and Fmr1
      mRNA levels, an inverse relationship with FMRP levels and Purkinje cell dropout
      that have not been seen in a previously described knock-in mouse model. In
      addition, these mice also show a differential deficit of FMRP in different parts
      of the brain that might account for symptoms of the full mutation that are seen
      in premutation carriers. As in humans, repeat instability is high with expansions
      predominating and, for the first time in a mouse model, large expansions into the
      full mutation range are seen that occur within a single generation. Thus,
      contrary to what was previously thought, mice may be good models not only for the
      symptoms seen in human carriers of FMR1 premutation alleles but also for
      understanding the mechanism responsible for repeat expansion, a phenomenon that
      is responsible for a number of neurological and neurodevelopmental disorders.

PMID- 17442506
TI  - SINEs, evolution and genome structure in the opossum.
AB  - Short INterspersed Elements (SINEs) are non-autonomous retrotransposons, usually
      between 100 and 500 base pairs (bp) in length, which are ubiquitous components of
      eukaryotic genomes. Their activity, distribution, and evolution can be highly
      informative on genomic structure and evolutionary processes. To determine recent
      activity, we amplified more than one hundred SINE1 loci in a panel of 43 M.
      domestica individuals derived from five diverse geographic locations. The SINE1
      family has expanded recently enough that many loci were polymorphic, and the
      SINE1 insertion-based genetic distances among populations reflected geographic
      distance. Genome-wide comparisons of SINE1 densities and GC content revealed that
      high SINE1 density is associated with high GC content in a few long and many
      short spans. Young SINE1s, whether fixed or polymorphic, showed an unbiased GC
      content preference for insertion, indicating that the GC preference accumulates
      over long time periods, possibly in periodic bursts. SINE1 evolution is thus
      broadly similar to human Alu evolution, although it has an independent origin.
      High GC content adjacent to SINE1s is strongly correlated with bias towards
      higher AT to GC substitutions and lower GC to AT substitutions. This is
      consistent with biased gene conversion, and also indicates that like chickens,
      but unlike eutherian mammals, GC content heterogeneity (isochore structure) is
      reinforced by substitution processes in the M. domestica genome. Nevertheless,
      both high and low GC content regions are apparently headed towards lower GC
      content equilibria, possibly due to a relative shift to lower recombination rates
      in the recent Monodelphis ancestral lineage. Like eutherians, metatherian
      (marsupial) mammals have evolved high CpG substitution rates, but this is
      apparently a convergence in process rather than a shared ancestral state.

PMID- 17442507
TI  - Toxicity of diazinon and its metabolites increases in diabetic rats.
AB  - The effect of diazinon (DZN) on the activities of cholinesterase (ChE) in plasma
      and acetylcholinesterase (AChE) in erythrocyte and brain was investigated in
      normal and streptozotocin-induced diabetic rats. Hepatic drug-metabolizing enzyme
      activity was also estimated by measuring the systemic clearance of antipyrine,
      and the expression of hepatic cytochrome P450 (CYP) 3A2 and CYP1A2, which is
      closely related to the metabolism from DZN to DZN-oxon, a strong inhibitor of
      both ChE and AChE. No significant differences in the activities of ChE in plasma
      and AChE in erythrocyte were observed between normal and diabetic rats. Treatment
      with DZN significantly decreased these activities in diabetic rats more than in
      normal rats 6h after injection (6.5 mg/kg). Treatment with DZN significantly
      decreased the activity of AChE in brain of diabetic rats than normal rats 3h
      after injection (65 mg/kg), although no significant difference in the activity
      was found between normal and diabetic rats. The urinary recovery of
      diethylphosphate (DEP), a metabolite of DZN-oxon, was significantly increased in
      diabetic rats, but that of diethylthiophosphate (DETP), a metabolite of DZN, was
      unchanged. Significant increases in the systemic clearance of antipyrine and
      protein levels of hepatic CYP1A2, not CYP3A2, were observed in diabetic rats.
      These results suggest the possibility that a metabolite of DZN, DZN-oxon, causes
      higher toxicity in diabetic rats due to the enhancement of hepatic CYP1A2
      mediated metabolism of DZN.

PMID- 17442508
TI  - Bovine platelet-activating factor acetylhydrolase (PAF-AH) activity related to
      fertility.
AB  - Plasma platelet-activating factor acetylhydrolase (PAF-AH), the enzyme
      characterized by the association with plasma lipoproteins, degrades platelet
      activating factor (PAF) as well as PAF-like oxidatively fragmented phospholipids
      produced during oxidative stress. Apart from pro-inflammatory properties, PAF is
      also related to reproductive processes and successful fertility. In order to get
      a better insight into the involvement of PAF-AH in the fertility of cows, the aim
      of the study was to determine the PAF-AH activity as well as the C-reactive
      protein, cholesterol and high density lipoprotein-cholesterol (HDL-C) in the
      serum of dairy cows throughout the pregnancy and lactation, as well as in
      infertile cows. The results showed that serum PAF-AH activity changes throughout
      pregnancy and lactation with a lower level during periparturient period. It is
      also found higher PAF-AH activity in lactating cows with reproductive disorders
      compared to high lactating cows without reproductive disorders. Strong
      correlation between PAF-AH activity and HDL-C concentration indicates that HDL
      could have considerable influence on PAF-AH activity in bovine plasma. CRP
      concentration was also lower during transition period suggesting that lactation
      might stimulate CRP synthesis in bovine. A higher CRP concentration in cows with
      reproductive disorders compared to fertile cows at the peak of lactation,
      demonstrates that milk production is not the only factor influencing CRP in cows.
      A significant correlation between PAF-AH activity and CRP level shows that both
      parameters could be influenced by reproductive status of dairy cows.

PMID- 17442509
TI  - Nanoscopic friction behavior of pharmaceutical materials.
AB  - The characteristics of various pharmaceutical dosage forms are influenced by
      surface properties such as the friction behavior. For example, die wall friction
      is a key issue in developing a solid dosage form. However, the friction
      properties are not completely understood mainly because of the lack of
      fundamental measurements. Herein, the friction behavior of pharmaceutical
      materials was investigated and compared with their adhesion behavior using atomic
      force microscopy. The sliding speed causes significant variations in the
      frictional force. Compared with other materials, lubricant materials showed less
      distinct differences in friction tests than in adhesion tests, indicating the
      dependence of the lubricant efficiency on the stress state. The three parameters
      obtained from the modified Amonton's law, i.e., absolute frictional force,
      friction coefficient and residual force, showed consistent trends. Overall, the
      friction behavior was not a direct reflection of the adhesion forces. The
      intrinsic friction behavior of a single pharmaceutical particle can be quantified
      using atomic force microscopy.

PMID- 17442510
TI  - Selective inducible nitric oxide synthase suppression by new bracteanolides from
      Murdannia bracteata.
AB  - Murdannia bracteata has been used as a Taiwanese folk medicine for its anti
      inflammatory properties. However, neither its active ingredients nor its anti
      inflammatory actions are well defined. Nitric oxide (NO), overproduced by
      activated macrophages via inducible NO synthase (iNOS), is suggested to be a
      significant pathogenic factor in various inflammatory tissue injuries. In order
      to elucidate the anti-inflammatory actions of M. bracteata, the present study was
      designed to isolate its active constituents and examine its effects on iNOS in
      lipopolysaccharide (LPS)-activated macrophages. Two new hydroxybutenolides,
      bracteanolide A (1) and B (2), together with (+)-(R)-p-hydroxyphenyllactic acid
      (3) and isovitexin (4), were isolated and identified from M. bracteata by the NO
      production assay. All of the compounds inhibited NO production except 3. Their
      rank order of potency was 1>2>4. Among these, 1 significantly inhibited NO
      production, which is associated with its suppression on iNOS induction in a
      concentration-dependent manner, with an IC(50) of 33.27+/-0.86 microM.
      Nevertheless, isometric tension recordings in isolated endothelium-intact rat
      aorta revealed that 1-4 did not affect acetylcholine-induced endothelial NO
      dependent relaxation, an index of endothelial NOS (eNOS) activity. The selective
      inhibition on iNOS provides a possible explanation for the anti-inflammatory use
      of M. bracteata.

PMID- 17442511
TI  - The selective effect of N-feruloylserotonins isolated from Leuzea carthamoides on
      nociception and anxiety in rats.
AB  - The effects of N-feruloylserotonins, substances isolated from the seeds of Leuzea
      carthamoides (WILLD.) DC., on nociception and anxiety were studied in Wistar
      rats. Nociceptive responses were measured using the plantar and tail-flick tests
      which were administered before and after swimming stress (3 min, water
      temperature 32 degrees C). Anxiety was evaluated using an elevated plus maze. In
      Experiment I, neither basal nociception nor stress-induced analgesia was
      influenced significantly. Separating the animals into groups based on their basal
      nociceptive sensitivity, either high- or low-pain threshold revealed that N
      feruloylserotonins have selective effects, especially on rats with high-pain
      thresholds. In these animals, N-feruloylserotonins reduced the stress-induced
      analgesia that followed swimming stress. In Experiment II, basal nociceptive
      sensitivity correlated with indicators of anxiety; high-pain threshold rats were
      more anxious in the elevated plus maze, with less frequent visits to open arms.
      The opposite effect was seen in low-pain threshold rats. N-feruloylserotonins did
      not influence anxiety in low-pain threshold rats, although it reduced anxiety in
      the high-pain threshold rats as indicated by the increased ratio of open arm
      visit frequency compared to closed arm visit frequency in the elevated plus maze.
      From these results we concluded that N-feruloylserotonins have selective stress
      reducing effects in stress-sensitive animals.

PMID- 17442512
TI  - Clinical systematic observation of Kangxin capsule curing vascular dementia of
      senile kidney deficiency and blood stagnation type.
AB  - OBJECTIVE: To observe the validity and safety of Kangxin capsule curing the
      patients with vascular dementia (VaD). PATIENTS AND METHODS: Fifty-six patients
      with vascular dementia of kidney deficiency and blood stagnation type were
      selected on the basis of defined diagnostic criteria and were randomly divided
      into Kangxin group (29) and control group (27), observing the relevant
      accumulation scores in dementia scale before and after treatment and changes of
      endothelin (ET), sex hormone, immunity and routine examinations. RESULTS: Kangxin
      capsule can effectively improve the symptom of patients with VaD of senile kidney
      deficiency and blood stagnation type, and the average value of curative effect
      index of 29 patients in the treatment group is 23.01>/=20%, i.e. effective;
      compared with that before treatment, both CD(4) and CD(4).CD(8)(-1) rises
      (P<0.05) after the treatment with Kangxin capsule; for the male VaD patients of
      the Kangxin group, T level increases (P<0.05) and estrodial (E(2)).testerone (T)(
      1) value decreases (P<0.05) after the treatment; for the female VaD patients of
      the Kangxin group, E(2), E(2).T(-1) value increases a great deal (P<0.05)
      compared with that before treatment; ET level of both groups decreased on average
      (P<0.01), and did not demonstrate any obvious toxic side effect. CONCLUSIONS:
      Kangxin capsule is a valid and safe preparation of Chinese traditional medicine
      for curing VaD of senile kidney deficiency and blood stagnation type.

PMID- 17442513
TI  - Anti-inflammatory activity of Dalbergia lanceolaria bark ethanol extract in mice
      and rats.
AB  - Topical anti-inflammatory activity of Dalbergia lanceolaria Linn. bark ethanol
      extract was demonstrated in albino mice using TPA-, EPP- and AA-induced ear edema
      models. The systemic activity of extract was confirmed using acute and sub-acute
      anti-inflammatory models in albino rats. The ethanol extract exhibited
      significant systemic anti-inflammatory activity in Carrageenan-induced rat paw
      edema, by inhibition of histamine and prostaglandin phases of acute inflammation.
      The extract also showed significant activity against turpentine-induced exudative
      changes and no activity against granular tissue formation in cotton pellet
      induced granuloma in albino rats. Thus, resultant anti-inflammatory activity
      might be due to effects on several mediators involving cyclo-oxygenase pathway
      resulting in prostaglandin formation and leukocyte migration from the vessels.

PMID- 17442514
TI  - Refractory epilepsy accompanying acute encephalitis with multifocal cortical
      lesions: possible autoimmune etiology.
AB  - We report on a 14-year-old male suffering from acute encephalitis, whose clinical
      course met the criteria for acute encephalopathy with refractory, repetitive
      partial seizures (AERRPS). He presented with extremely refractory partial and
      secondary generalized seizures, and required high-dose barbiturate infusion
      therapy for 57 days under mechanical ventilation. Seven weeks after onset, the
      seizures were ameliorated by treatment with sodium bromide, carbamazepine,
      clobazam, and high-dose phenobarbital. Magnetic resonance imaging on day 14 of
      admission showed multifocal cortical lesions scattered in the bilateral
      hemispheres; these disappeared on day 34. Diffuse and mild atrophy of the
      cerebral cortex, and moderate atrophy of the hippocampus, appeared by day 61.
      Serum anti-glutamate receptor epsilon2 autoantibodies were detected on day 2. The
      patient was discharged after 113 days of admission with intractable epilepsy,
      memory disability, and regression of intelligence. We discuss the etiological
      significance of the multifocal lesions, which are unusual findings on
      neuroimaging of AERRPS.

PMID- 17442515
TI  - [Compensation of malignant mesothelioma as an occupational disease in Lower
      Normandy, from 1995 to 2002].
AB  - BACKGROUND: Despite the close relation between occupational exposure to asbestos
      and malignant mesothelioma, the compensation of this disease is still far from
      being the rule. The objective of this study is to assess the compensation process
      of all the cases of occupational mesothelioma recorded by the regional
      mesothelioma registry between September 1995 and August 2002, and to make
      suggestions for improvement of the compensation of future cases. METHODS:
      Lifetime exposure to asbestos was assessed for each of the 141 mesothelioma cases
      observed in Lower Normandy during this time period, and 105 cases could be
      related to a possible, probable, or very probable occupational exposure to this
      mineral. Data about notification and compensation of these occupational diseases
      were gathered with the help of all health insurance organisms concerned. RESULTS:
      Except for five cases in which insurance conditions did not allow any
      compensation, compensation of occupational mesothelioma occurred in 85% of the
      cases. This high rate was probably the result of the existence of an early
      asbestos industry in this region, and of the particular awareness of the Norman
      population about asbestos-related diseases, as well as of the epidemiological
      follow-up of mesothelioma in Lower Normandy. When notified for compensation, all
      cases but one were actually compensated, and the lag-time between notification
      and compensation proved to decrease since 1995, with an average delay reaching
      91,1 days in 2002. Patients who did not report their disease were older than
      those who did, and the lack of knowledge of medical practitioners about
      compensation procedures seems to be an important matter in this issue.
      CONCLUSION: In order to improve the rate of compensation of occupational
      malignant mesothelioma cases, information about the usual occupational origin of
      the disease should be delivered systematically to the general practitioner of
      each patient. This could be done by pathologists, when they diagnose malignant
      mesothelioma, and/or by medical examiners when sickness benefits are sought, or
      even by the epidemiological center of death causes (INSERM, CepiDc), for the
      beneficiaries of patients who died from malignant mesothelioma.

PMID- 17442516
TI  - [Risk of hepatitis C related to traditional medicine: a case control study in Ho
      Chi Minh City, Vietnam].
AB  - BACKGROUND: The transmission of hepatitis C virus (HCV) is strongly associated
      with blood transfusion and drug abuse. However, in about a third of HCV-infected
      subjects, the risk factors are not clearly identified though some cases are
      likely to be healthcare associated. In an Asian country such as Vietnam, invasive
      procedures used for traditional and beauty care could be potential risk factors.
      The aim of the present study was to identify the risk factors of HCV infection in
      a population sample in Ho Chi Minh City. METHOD: A case-control study matched by
      gender and age was performed among blood adults donors at the Centre of
      hematological diseases and blood transfusion. Cases were defined as blood donors
      with HCV-positive Elisa. Controls were selected at random among ELISA HCV
      negative donors. A standardized questionnaire was used to collect data focusing
      on invasive medical procedures, beauty care and on invasive procedures related to
      traditional medicine. RESULT: Among the 80 cases and 240 controls, the
      independent predictors of anti-HCV positivity using a stepwise logistic
      regression were: blood transfusion, intravenous drug abuse, acupuncture,
      ventoused scarification and practice of scarification (adjusted odds ratio and
      IC95%: 3.8 [1.1-13.1], 3.5 [1.7-7.3], 5.4 [2.3-12.7], 5.4 [2.5-11.7], 6.6 [1.6
      26.4] respectively). The other risk factors such as past hospitalization surgery,
      tattooing, being a healthcare worker, or practising tattooing or piercing were
      not associated with HCV infection. CONCLUSION: To be exposed to ventoused
      scarifications or acupuncture are risk factors for the transmission of HCV in
      Vietnam. A wide information campaign on hygiene practices for general population
      as well as the practitioners is needed to ensure safer health cares in
      traditional medicine.

PMID- 17442517
TI  - Aging cochleas in the F344 rat: morphological and functional changes.
AB  - The Fischer 344 rat strain has been frequently used as an animal model of rapid
      aging. The present study was aimed at evaluating the incidence of apoptotic cells
      in the inner ear of 20-24-month-old F344 rats and to correlate it with cochlear
      function using otoacoustic emissions. Staining with cresyl violet and the
      enzymatic labeling (terminal deoxynucleotidyl transferase, TdT) of fragmented DNA
      revealed large numbers of apoptotic cells in the marginal and basal layers of the
      stria vascularis and in adjacent cells of the spiral ligament. The amplitudes of
      distortion products otoacoustic emissions (DPOAEs), which reflect functional
      state of the outer hair cells, were significantly reduced or totally absent in
      these animals. In contrast to old F344 rats, no marked DPOAE amplitude reduction
      and smaller numbers of apoptotic cells were found in young 4-month-old F344 rats
      or in aged 24-28-month-old Long Evans rats. The accumulation of apoptotic cells,
      mainly in the basal layer of the stria vascularis and in adjacent cells of the
      spiral ligament, leads to a detachment of the stria vascularis from the spiral
      ligament and results in the impairment of outer hair cell function. This specific
      type of strial deterioration suggests that aged F344 rats can serve as an animal
      model of strial presbycusis.

PMID- 17442518
TI  - Quantitative evaluation for brain CT/MRI coregistration based on maximization of
      mutual information in patients with focal epilepsy investigated with subdural
      electrodes.
AB  - Patients with drug-resistant focal epilepsy may require intracranial
      investigations with subdural electrodes. These must be correctly localized with
      respect to the brain cortical surface and require appropriate monitoring. For
      this purpose, coregistration techniques, which fuse preimplantation 3D magnetic
      resonance imaging scans with postimplantation computed tomography scans, have
      been implemented. In order to reduce localization errors due to the fusion
      process, we used a coregistration method based on the maximization of mutual
      information (MI) in 11 patients with extratemporal epilepsy who were invasively
      investigated. Our registration method is based on three processing steps: rigid
      body transformation for coregistration, computation of MI as a similarity measure
      and the use of the Downhill Simplex optimization method. After consistency
      analysis, the shift of the registration method reached 0.14+/-0.27 mm in
      translation and 0.03+/-0.14 degrees in rotation, and the accuracies assessed on
      voxels of skull surface and voxels of the center of the brain volume were 1.42+/
      0.61 and 1.15+/-0.53 mm, respectively. The accuracy of the fusion process reached
      submillimeter range, and results were considered reliable for surgical planning
      in all studied patients.

PMID- 17442519
TI  - Effects of cocaine on blood flow and oxygen metabolism in the rat brain:
      implications for phMRI.
AB  - The effects of cocaine on cerebral blood flow and tissue oxygen levels in the rat
      brain were investigated with concurrent laser Doppler flowmetry and fluorescence
      quenching spectroscopy. Responses elicited by mild hypercapnia were used as
      calibration to assess the effects of cocaine on oxidative metabolism. Intravenous
      cocaine challenge of 0.5 mg/kg induced significant increases in tissular
      oxygenation and perfusion in all regions investigated (primary motor cortex,
      medial prefrontal cortex and dorsal striatum). Mild hypercapnia, a challenge that
      affects haemodynamics but not metabolism, elicited comparable changes in blood
      flow but substantially larger changes in tissue oxygen levels. These differences
      in tissue oxygen build-up suggest that increased oxidative metabolism is a
      significant component of the cerebral metabolic response to acute cocaine
      challenge. The implications for the interpretation of pharmacological MRI data
      are discussed.

PMID- 17442520
TI  - Complimentary aspects of diffusion imaging and fMRI: II. Elucidating
      contributions to the fMRI signal with diffusion sensitization.
AB  - Tissue water molecules reside in different biophysical compartments. For example,
      water molecules in the vasculature reside for variable periods of time within
      arteries, arterioles, capillaries, venuoles and veins, and may be within blood
      cells or blood plasma. Water molecules outside of the vasculature, in the
      extravascular space, reside, for a time, either within cells or within the
      interstitial space between cells. Within these different compartments, different
      types of microscopic motion that water molecules may experience have been
      identified and discussed. These range from Brownian diffusion to more coherent
      flow over the time scales relevant to functional magnetic resonance imaging
      (fMRI) experiments, on the order of several 10s of milliseconds. How these
      different types of motion are reflected in magnetic resonance imaging (MRI)
      methods developed for "diffusion" imaging studies has been an ongoing and active
      area of research. Here we briefly review the ideas that have developed regarding
      these motions within the context of modern "diffusion" imaging techniques and, in
      particular, how they have been accessed in attempts to further our understanding
      of the various contributions to the fMRI signal changes sought in studies of
      human brain activation.

PMID- 17442521
TI  - Regional brain activity after prolonged cholinergic enhancement in early
      Alzheimer's disease.
AB  - This functional magnetic resonance imaging (fMRI) study examined changes in brain
      activation after prolonged (20 weeks) and stabilized treatment with the
      cholinesterase inhibitor galantamine in a small group of patients with very mild
      Alzheimer's disease (AD). Two cognitive activation paradigms were chosen: one
      requiring semantic association and the other relying on attention and requiring
      target detection. A group of age- and education-matched healthy controls was also
      scanned for comparison. A modest (but not statistically significant) improvement
      in behavioral scores after treatment was observed in both fMRI tasks. There were
      brain activation increases in the semantic association task after treatment, and
      the differences in brain activation present in the comparison of AD patients'
      baseline images with those of controls were not detectable after treatment. In
      the target detection task, regions that were activated in the elderly controls
      but not in the baseline images of the AD group also showed significant activation
      after treatment. Overall, however, the increases were modest and might reflect
      the heterogeneity of clinical response to treatment in this small group. Future
      pharmacological fMRI studies should include clinical response as a factor in the
      analysis of cholinergic enhancement effects in AD patients.

PMID- 17442522
TI  - Image registration framework for large-scale longitudinal MRI data sets: strategy
      and validation.
AB  - Advanced magnetic resonance imaging (MRI) studies often require the
      transformation of large numbers of images into a common space. Calculating
      transformations that relate each image to every other and applying them to the
      images on demand are theoretically possible; however, these can be
      computationally prohibitive. Therefore, relating each image to only one other
      image, then linking those transforms together to relate any two images in the
      database, may be an efficient alternative. Evaluated were the feasibility and
      validity of image registration to bring intraindividual MR images into mutual
      correspondence for longitudinal analysis through the concatenation of precomputed
      transforms. A longitudinal data set of 10 multiple sclerosis patients with nine
      serial dual-echo spin-echo, 1.5-T MRI scans was used. Intrasubject registrations
      were performed stepwise between consecutive images and direct from each time
      point to the baseline. Consecutive transforms were concatenated and evaluated
      against direct registrations by comparing the resulting transformed images (using
      Pearson correlation coefficient). Confounding variables such as time between
      scans, brain atrophy, and change in lesion load were evaluated. We found the
      images resampled with the direct and the concatenated transforms to be highly
      correlated, and there was no significant difference between methods. Differences
      in brain parenchymal fraction (a measure of brain atrophy) showed significant
      inverse correlation with the correspondence of the resampled images. Results
      indicate that concatenating multiple transforms that link two images together
      produces near-identical results to that of direct registration; thus, this method
      is both useful and valid.

PMID- 17442523
TI  - A framework for quality control and parameter optimization in diffusion tensor
      imaging: theoretical analysis and validation.
AB  - In this communication, a theoretical framework for quality control and parameter
      optimization in diffusion tensor imaging (DTI) is presented and validated. The
      approach is based on the analytical error propagation of the mean diffusivity
      (D(av)) obtained directly from the diffusion-weighted data acquired using
      rotationally invariant and uniformly distributed icosahedral encoding schemes.
      The error propagation of a recently described and validated cylindrical tensor
      model is further extrapolated to the spherical tensor case (diffusion anisotropy
      approximately 0) to relate analytically the precision error in fractional tensor
      anisotropy (FA) with the mean diffusion-to-noise ratio (DNR). The approach
      provided simple analytical and empirical quality control measures for
      optimization of diffusion parameter space in an isotropic medium that can be
      tested using widely available water phantoms.

PMID- 17442524
TI  - Zero and first-order phase shift correction for field map estimation with dual
      echo GRE using bipolar gradients.
AB  - A simple phase error correction technique used for field map estimation with a
      generally available dual-echo gradient-echo (GRE) sequence is presented. Magnetic
      field inhomogeneity maps estimated using two separate GRE volume acquisitions at
      different echo times are prone to dynamic motion errors between acquisitions. By
      using the dual-echo sequence, the data are collected during two back-to-back
      readout gradients in opposite polarity after a single radio frequency pulse, and
      interecho motion artifacts and alignment errors in field map estimation can be
      factored out. Residual phase error from the asymmetric readout pulses is modeled
      as an affine term in the readout direction. Results from phantom and human data
      suggest that the first-order phase correction term stays constant over time and,
      hence, can be applied to different data acquired with the same protocol over
      time. The zero-order phase correction term may change with time and is estimated
      empirically for different scans.

PMID- 17442525
TI  - Pharmacological modulation of functional connectivity: the correlation structure
      underlying the phMRI response to d-amphetamine modified by selective dopamine D3
      receptor antagonist SB277011A.
AB  - Pharmacological MRI (phMRI) experiments utilise fMRI time series methods to map
      the central effect of pharmaceutical compounds. The typical univariate maps may,
      however, integrate the effects of several different neurotransmitter systems or
      underlying mechanisms. The results may thus be spatially and/or mechanistically
      nonspecific. Intersubject correlation analysis based on the phMRI response
      amplitude can more directly identify patterns of functional connectivity
      underlying the central effects of an acutely administered compound. In this
      article, we extend this approach to experiments where the effects of one compound
      in modulating the response to another are of interest. Specifically, we show a
      modulation of the correlation structure of a probe compound (d-amphetamine) by
      pretreatment with the selective dopamine D3 receptor antagonist SB277011A in the
      rat. The strongest modifications in the correlation patterns occurred in
      connection with the ventral tegmental area, the source of mesolimbic dopamine
      projections and a key substrate in the reward system.

PMID- 17442526
TI  - Magnetic resonance angiographic demonstration of carotid-cavernous fistula using
      elliptical centric time resolved imaging of contrast kinetics (EC-TRICKS).
AB  - Magnetic resonance angiographic evaluation of the intracranial vasculature has
      been predominantly carried out using conventional angiographic techniques such as
      time of flight and phase contrast sequences. These techniques have good spatial
      resolution but lack temporal resolution. Newer faster angiographic techniques
      have been developed to circumvent this limitation. Elliptical centric time
      resolved imaging of contrast kinetics (EC-TRICKS) is one such technique which has
      combined the use of elliptical centric ordering of the k-space with multiphase 3D
      digital subtraction MR angiogram (MRA) to achieve excellent temporal resolution
      of the arterial and venous circulations. Its applications have been mainly in the
      peripheral vasculature. We report the use of this technique in a case of a high
      flow, direct carotid-cavernous fistula to demonstrate its potential in
      intracranial MR angiography.

PMID- 17442527
TI  - Structural analysis of photo-degradation in thiazole-containing compounds by LC
      MS/MS and NMR.
AB  - The photo-degradation behavior of a pharmaceutical compound previously under
      development for treatment of overactive bladder was studied. Samples of {4-(4
      chloro-3-fluorophenyl)-2-[4-(methyloxy)phenyl]-1,3-thiazol-5-yl} acetic acid were
      stressed with visible light and were observed to degrade into a single primary
      photo-degradation product. This unknown product was analyzed by liquid
      chromatography tandem mass spectrometry (LC-MS/MS) with accurate mass measurement
      and hydrogen/deuterium exchange to determine its molecular weight and formula,
      isotope distribution patterns and exchangeable protons, and product ion
      structures. By comparison of the fragmentation pathways of the protonated and
      sodiated species, the charge was found to locate in the electron-rich part of the
      molecule after fragmentation. MS-derived structural information combined with
      stopped-flow 1H LC-nuclear magnetic resonance (NMR) analysis suggested that the
      degradation product was 4-chloro-N-(4-methoxybenzoyl)-3-fluorobenzamide. This
      unique photo-degradation product was subsequently isolated using preparative
      scale chromatography, and its structure was confirmed using 1D and 2D NMR
      techniques involving the 1H, 13C, 15N and 19F nuclei. The structure of this
      product suggests that {4-(4-chloro-3-fluorophenyl)-2-[4-(methyloxy)phenyl]-1,3
      thiazol-5-yl} acetic acid has reacted with singlet oxygen (1Deltag) via a [4+2]
      Diels-Alder cycloaddition upon photo-irradiation to cause photo-oxygenation in
      the solid-state (as is common in solution phase), resulting in an unstable
      endoperoxide that rearranges to the final degradation product structure. Photo
      degradation of a structurally related thiazole, 4-(4-Chlorophenyl)thiazol-2
      amine, proceeded via a similar process but in a less reactive manner. However,
      when exposed to the same conditions, sulfathiazole did not degrade, indicating
      that this photo-degradation process may only occur for thiazole-containing
      compounds with specific substituents, such as aryl rings.

PMID- 17442528
TI  - Physician delivery of smoking prevention counseling to young patients in the
      United Arab Emirates.
AB  - OBJECTIVE: To describe the delivery of smoking preventive counseling to
      preadolescent, adolescent, and young adult patients in an Arab population, and to
      examine counseling behavior according to physician demographic characteristics
      and perceived barriers to counseling. METHODS: A cross-sectional mail survey was
      carried out among general practitioners (GPs) in private practice in the Emirates
      of Sharjah, Dubai and Abu Dhabi. RESULTS: Of 391 eligible GPs, 218 (56%)
      completed the questionnaire. Overall 29, 50 and 65% of GPs offered preventive
      advice to preadolescents (9-12 years), adolescents (13-19 years) and young adults
      (20-24 years), respectively. Lack of patient educational materials was cited by
      71.8% of GPs as a very important barrier to offering smoking prevention
      counseling, followed by lack of community resources (66.5%) and lack of time
      (62.2%). Older age, male gender, and having knowledge of the stages of change
      were positively associated with offering preventive advice. CONCLUSION: Physician
      self-reports of their smoking prevention counseling practices suggest there is
      opportunity for improvement. More training and support is needed to improve and
      encourage physician adherence to current smoking prevention counseling
      guidelines. PRACTICE IMPLICATION: More research is needed to determine the most
      effective method to improve delivery of preventive care by GPs, and to
      communicate appropriate preventive or cessation messages.

PMID- 17442529
TI  - A small mammal model of tumour implantation, dissemination and growth factor
      expression after partial hepatectomy.
AB  - BACKGROUND: Surgical resection remains the most effective therapy for metastatic
      colorectal cancer confined to the liver, although the extrahepatic recurrence
      rate is high. AIM OF THE STUDY: To develop a mammal model in order to investigate
      by which mechanisms liver surgery affects distant tumour recurrence. METHODS: In
      this animal study the effect of partial hepatectomy (phX) on the development of
      tumour noduli in the lungs was evaluated. CC531 rat colon carcinoma cells were
      inoculated i.v. 24h before, during or 24h after surgery. Rat serum was obtained
      at different time-points after phX and added to in vitro CC531 cell cultures.
      Finally, phX was compared with an ileum resection (ilX). RESULTS: phX leads to
      increased tumour noduli in the lungs, compared to Sham operation (p=0.002), but
      only when performed directly before the injection of tumour cells and not when
      performed 24h before or after the inoculation. Comparable results were obtained
      for ilX. No growth stimulation of tumour cells after incubation with rat serum,
      obtained at different time-points after phX, could be detected in vitro.
      CONCLUSION: Not only phX, but also surgery, in general promotes distant tumour
      recurrence exerting the effect during the early phase of tumour cell adhesion and
      not during tumour outgrowth.

PMID- 17442530
TI  - Primary intrapulmonary thymoma: a systematic review.
AB  - AIM: This article reviews the literature on the clinical features, diagnosis and
      management of primary intrapulmonary thymoma. METHODS: Medline, Embase and
      Cochrane Library searches were performed on all relevant Anglo-Saxon language
      articles. The search words included "primary pulmonary thymoma" and
      "intrapulmonary thymoma". Secondary references were obtained from key articles.
      Prognostic and treatment strategies were analyzed by the Kaplan-Meier method,
      comparisons between curves were made using log rank test. RESULTS: The searches
      yielded 25 cases of primary intrapulmonary thymoma. Median follow-up was 9 months
      (1 day to 13 years). At follow-up, 14 patients were tumor free, one patient had a
      local recurrence 8 years after radiotherapy, one patient responded favorably to
      radiotherapy, six patients died and three patients were lost to follow-up. The
      presence of a paraneoplastic syndrome decreased survival (P=0.02), however,
      histological subgroup (P=0.216), clinical stage (P=0.63) and tumor size (P=0.288)
      did not affect survival. Survival in surgically managed patients was
      significantly better than in conservatively managed patients (P=0.039). Adjuvant
      radiotherapy did not provide any benefit (P=0.4). CONCLUSION: Complete resection
      of primary intrapulmonary thymomas appears sufficient in non-malignant tumors.
      Because of the risk of late local recurrence, long-term regular clinical follow
      up is warranted.

PMID- 17442531
TI  - 'Radioguided occult lesion localisation' (ROLL) for non-palpable breast lesions:
      a review of the relevant literature.
AB  - BACKGROUND: 'Radioguided occult lesion localisation' (ROLL) is a possible
      alternative to the commonly used 'wire-guided localisation' (WGL) of non-palpable
      breast lesions. Intratumoural injection of a radiotracer identifies both the
      primary tumour and the sentinel lymph nodes for intraoperative gamma probe guided
      dissection. METHOD: A broad literature search was conducted, using the Pubmed,
      Embase and The Cochrane Library databases. Five clinically controlled trials and
      one randomised controlled trial, all of modest size, were selected which describe
      both ROLL and WGL. Four articles were found that describe the combined use of the
      ROLL technique with the sentinel node procedure. RESULTS: In the ROLL group
      between 69% and 84% of the lesions were radically excised, compared with 44-60%
      of the lesions in the WGL group. The studies that combined ROLL and the sentinel
      node procedure mentioned even higher percentages of radically excised specimens
      ranging from 90% to 95% and an identification rate of sentinel nodes up to 100%.
      One randomised controlled trial mentioned that the ROLL procedure had a faster
      localisation time, was easier to perform, was less painful and gave a better
      cosmetic result than WGL. CONCLUSION: ROLL seems a promising technique, which
      appears to be more radical than WGL. Localisation tends to be more accurate and
      faster, the excision procedure is more elegant and simple to perform, and the
      cosmetic result seems to be better. Further research is necessary to establish
      the exact role of ROLL in the management of non-palpable breast lesions.

PMID- 17442532
TI  - Treatment results for gastric cancer surgery: 12 years' experience at a single
      institute in Korea.
AB  - AIMS: To evaluate the changing trends of clinicopathologic features, surgical
      procedures and treatment outcomes of gastric cancer in a large-volume center.
      METHODS: We divided the time period into two parts: the first is 1989-1996
      (period I) and the second is 1997-2001 (period II). Then we analyzed
      prospectively collected data on 1816 patients treated at Kangnam St. Mary's
      Hospital, The Catholic University of Korea, from 1989 to 2001. RESULTS: Upper one
      third cancer was seen more prevalently in period II than period I (9.4% versus
      6.6%) (p=0.000) and total gastrectomy was performed more frequently in period II
      than period I (25% versus 18%) (p=0.000). A diagnosis of early gastric cancer was
      made more prevalently in period II than period I (40% versus 27%) (p=0.000). D2
      lymphadenectomy was done in 74% of the period I patients and 83% of their period
      II counterparts (p=0.000). Between the two periods, there was a significant
      difference in the incidence of operation-related major complications (9.9% in
      period I versus 3.9% in period II) (p=0.000) and the mortality (1.8% versus 0.6%)
      (p=0.023). The overall 5-year and 10-year survival rates were significantly
      higher in period II than period I (63% and 57% in period I versus 69% and 64% in
      period II) (p=0.009). CONCLUSIONS: The overall survival of gastric cancer
      significantly increased because of the early detection and aggressive surgical
      approaches by experienced surgeons in a large-volume center. More effective
      multidisciplinary approaches are warranted to improve the prognosis of advanced
      gastric cancer.

PMID- 17442533
TI  - [Reference centers for rare respiratory diseases].

PMID- 17442534
TI  - [Fibromuscular dysplasia].
AB  - Fibromuscular dysplasia is an idiopathic, segmental, nonatherosclerotic and
      noninflammatory disease of the muscle layer of arterial walls that leads to
      stenosis of small- and medium-sized arteries. Fibromuscular dysplasia
      preferentially affects young women. Although it can affect every arterial tree,
      it most often touches the renal and internal carotid arteries. Renal
      fibromuscular dysplasia can cause hypertension by stenosis of the renal artery,
      most often seen on angiography as resembling a "pearl necklace". Cerebrovascular
      fibromuscular dysplasia becomes symptomatic when the arterial stenosis is tight
      and causes hypoperfusion, embolism, or thrombosis or when arterial dissection or
      rupture of the associated aneurysm occurs.

PMID- 17442535
TI  - [Sleep apnea syndrome and heart failure].
AB  - More than half of all patients with stable heart failure are affected by sleep
      apnea syndrome. The mechanism of apnea may be either obstructive, by collapse of
      the upper airways, or central with nocturnal Cheyne-Stokes respiration. Changes
      in intrathoracic pressure, awakening and hypoxemia all lead to an increase in
      left ventricular afterload and to sympathetic activation, which can aggravate
      heart failure and prognosis. Treatment with positive pressure ventilation
      improves symptoms as well as cardiac function and prognosis. Sleep respiratory
      disorders are underdiagnosed and undertreated in patients with stable heart
      failure. To improve management of sleep apnea, patients with stable heart failure
      should be screened with small outpatient oximeters.

PMID- 17442536
TI  - Diversity of olfactomedin proteins in the sea urchin.
AB  - Olfactomedin (OLF) domain proteins maintain extracellular protein-protein
      interactions in diverse phyla. Only one OLF family member, amassin-1, has been
      described from the sea urchin Strongylocentrotus purpuratus, a basal invertebrate
      deuterostome. Amassin-1 mediates intercellular adhesion of coelomocytes
      (immunocytes). Here we describe the protein structural features of four
      additional OLF proteins, the total for the genome being five. Phylogenetically,
      four of these proteins (the amassins) form a subgroup among previously identified
      OLF proteins. The fifth OLF protein is within the colmedin subfamily and contains
      a type II transmembrane domain, collagen repeats, and an OLF domain. Sea urchin
      OLF proteins represent an intermediate diversification between protostomes and
      vertebrates. Transcripts of all five OLF family members are in coelomocytes and
      adult radial nerve tissue. Transcripts for some OLF proteins increase during late
      larval stages. Transcript levels for amassin-1 increase 1,000,000-fold,
      coinciding with formation of the adult urchin rudiment within the larval body.

PMID- 17442537
TI  - Detection of polymorphisms in bovine toll-like receptors 3, 7, 8, and 9.
AB  - The toll-like receptors (TLRs) detect molecular signatures of invaders known as
      pathogen-associated molecular patterns (PAMPs). Ten members of the TLR family
      have been identified in cattle to date and 4 of these recognize PAMPs specific to
      viruses (TLRs 3, 7, 8, 9). The objective of this work was to detect polymorphisms
      in the genomic sequences of bovine TLRs 3, 7, 8, and 9. To achieve this
      objective, a panel of nine breeds representing Bos taurus and Bos indicus was
      assembled for sequencing and comparison with the Bovine Genome Project sequence.
      Comparative sequence analysis revealed a total of 139 polymorphisms, which
      include single-nucleotide polymorphisms and insertion-deletion polymorphisms. Of
      the 139 polymorphisms, 88% (N=123) are novel. In addition, the protein domain
      architecture of these four TLRs was examined between human, mouse, cow, and dog,
      which revealed several regions of conservation in the TLR variable leucine-rich
      repeat patterning.

PMID- 17442538
TI  - A modular neural network architecture for step-wise learning of grasping tasks.
AB  - This paper proposes a neural network architecture for learning of grasping tasks.
      The multineural network model presented in this work, allows acquisition of
      different neural representations of the grasping task through a successive
      learning over two stages in a strategy that uses already learned representations
      for the acquisition of the subsequent knowledge. Systematic computer simulations
      have been carried out in order to test learning and generalization capabilities
      of the system. The neural activity at different subparts of the artificial neural
      network during its performance phase, is compared to the activity of populations
      of real neurons in areas AIP and F5 of the distributed parieto-frontal biological
      neural network involved in visual guidance of grasping. A more biologically
      plausible development of the model presented here is also discussed. The proposed
      model can be also used as a high level controller for a robotic dextrous hand
      during learning and execution of grasping tasks.

PMID- 17442539
TI  - Epicutaneous (EC) immunization with myelin basic protein (MBP) induces
      TCRalphabeta+ CD4+ CD8+ double positive suppressor cells that protect from
      experimental autoimmune encephalomyelitis (EAE).
AB  - Multiple sclerosis (MS) is a central nervous system (CNS) chronic inflammatory
      autoimmune disease with limited treatment modalities. Oral tolerance is one of
      the experimental methods that protects from autoimmune diseases. However, this
      method failed to be therapeutic in clinical trials. In our previous work we found
      that epicutaneous (EC) immunization with protein antigen induced a state of
      profound immunosuppression that inhibited inflammatory response in contact
      sensitivity, in experimental autoimmune encephalomyelitis (EAE) and in allogeneic
      skin graft rejection. In our current work, we precisely determined the phenotype
      of EC induced T suppressor (Ts) cells that reduce the progress of EAE. Employing
      TCRdelta-/-, CD1d-/- mice, we showed that EC induced Ts cells do not belong
      either to the population of TCRgammadelta cells or CD1d restricted NKT cells.
      Moreover, we noticed that a lack of CD1d-/- restricted NKT lymphocytes resulted
      in the induction of much stronger suppression of EAE than in wild type mice. This
      might suggest that NKT cells could interfere with the induction of Ts cells.
      Using beta2m-/- mice, negative selection and positive selection of EC induced Ts
      cells, we showed that Ts cells protecting from EAE belong to the population of
      TCRalphabeta+ CD4+ CD8+ double positive lymphocytes.

PMID- 17442541
TI  - Continuous infusion of beta-lactam antibiotics in severe infections: a review of
      its role.
AB  - Continuous infusion of beta-lactam antibiotics has been widely promoted to
      optimise their time-dependent activity. Increasing evidence is emerging
      suggesting potential benefits in patient populations with altered
      pathophysiology, such as seriously ill patients. From a pharmacokinetic
      viewpoint, much information supports higher trough concentrations of beta-lactam
      antibiotics when administered by continuous infusion. This advantage of
      continuous infusion translates into a superior ability to achieve pharmacodynamic
      targets, particularly when the minimum inhibitory concentration (MIC) of the
      pathogen is >or=4 mg/L. One drawback of continuous infusion may be limited
      physicochemical stability. This issue exists particularly for carbapenem
      antibiotics whereby prolonged infusions (i.e. >3h) can be used to improve the
      time above the MIC compared with conventional bolus dosing. Few studies have
      examined clinical outcomes of bolus and continuous dosing of beta-lactam
      antibiotics in seriously ill patients. No statistically significant differences
      have been shown for: mortality; time to normalisation of leukocytosis or pyrexia;
      or duration of mechanical ventilation, intensive care unit stay or hospital stay.
      Some evidence suggests improved clinical cure and resolution of illness with
      continuous infusion in seriously ill patients. Pharmacoeconomic advantages of
      continuous infusion of beta-lactam antibiotics are well characterised. Available
      data suggest that seriously ill patients with severe infections requiring
      significant antibiotic courses (>or=4 days) may be the subgroup that will achieve
      better outcomes with continuous infusion.

PMID- 17442540
TI  - DNA fragmentation is increased in non-GABAergic neurons in bipolar disorder but
      not in schizophrenia.
AB  - Apoptosis is thought to contribute to neuronal loss in bipolar disorder and
      schizophrenia, although empiric evidence in support of this idea has been
      lacking. In this study, we investigated whether or not apoptosis is associated
      with GABAergic interneurons in the anterior cingulate cortex in schizophrenia
      (n=14) and bipolar disorder (n=14) when compared to normal controls (n=14). A
      double-labeling technique using the Klenow method of in situ end-labeling (ISEL)
      of single-stranded DNA breaks was combined with an in situ hybridization
      localization of mRNA for the 67 kDa isoform of glutamate decarboxylase (GAD67)
      and applied to the anterior cingulate cortex of 14 normal controls, 14
      schizophrenics, and 14 patients with bipolar disorder matched for age and
      postmortem interval. An increase in Klenow-positive, GAD67-negative nuclei were
      observed in layer V/VI of patients with bipolar disorder, but not schizophrenics.
      Klenow-positive cells that were also positive for GAD67 mRNA did not show
      differences in either patient group. CONCLUSIONS: This is the first demonstration
      that there is more DNA fragmentation in cells showing no detectable GAD67 mRNA in
      patients with bipolar disorder than in schizophrenics or controls. These findings
      suggest that non-GABAergic cells may be selectively vulnerable to oxidative
      stress in patients with bipolar disorder.

PMID- 17442542
TI  - OKP-B-14, a new OKP-B variant isolated from Klebsiella pneumoniae in Brazil.

PMID- 17442543
TI  - Differential effects of classical and atypical antipsychotic drugs on rotenone
      induced neurotoxicity in PC12 cells.
AB  - Although classical and atypical antipsychotics may have different effects against
      neurotoxicity, the underlying mechanisms remain to be elucidated. In the present
      study, we compared the atypical agents, risperidone (RIP), olanzapine (OLZ), and
      quetiapine (QTP), with the classical agent haloperidol (HAL) in reducing
      cytotoxicity induced by rotenone, a mitochondrial complex I inhibitor, in PC12
      cells. We also determined whether there were differential effects of RIP and HAL
      on the expression of brain-derived neurotrophic factor (BDNF), signal transducers
      and activators of transcription-3 (STAT-3), and the immediate early gene c-fos,
      as well as intracellular levels of calcium. Exposure to 6 muM rotenone for 24 h
      resulted in a significant decrease in cell viability and apoptotic alteration.
      The rotenone-induced cytotoxicity was dose-dependently worsened by pretreatment
      with HAL, but significantly improved by the aforementioned atypical agents at low
      doses. Real-time PCR analysis revealed that HAL pretreatment significantly
      increased BDNF mRNA expression but did not alter c-fos and STAT-3 expression
      compared to rotenone-exposed cells. Unlike HAL, RIP pretreatment produced a
      significant elevation of all the three substance mRNA expression and the
      expression intensity was 2.6- to 4.6-fold greater than HAL. Pretreatment with
      RIP, but not HAL, also effectively prevented an elevation of intracellular levels
      of calcium provoked by rotenone. These results suggest that the protective
      effects of atypical antipsychotics are associated with a greater capacity to
      enhance pro-cell survival factors, therapeutic biomarker expression, and blockade
      of calcium influx. This may provide an alternative for explaining therapeutic
      advantages of atypical agents observed in clinical use.

PMID- 17442544
TI  - Squeeze involvement in the specification of Drosophila leucokinergic neurons:
      Different regulatory mechanisms endow the same neuropeptide selection.
AB  - One of the most widely studied phenomena in the establishment of neuronal
      identity is the determination of neurosecretory phenotype, in which cell-type
      specific combinatorial codes direct distinct neurotransmitter or neuropeptide
      selection. However, neuronal types from divergent lineages may adopt the same
      neurosecretory phenotype, and it is unclear whether different classes of neurons
      use different or similar components to regulate shared features of neuronal
      identity. We have addressed this question by analyzing how differentiation of the
      Drosophila larval leucokinergic system, which is comprised of only four types of
      neurons, is regulated by factors known to affect expression of the FMRFamide
      neuropeptide. We show that all leucokinergic cells express the transcription
      factor Squeeze (Sqz). However, based on the effect on LK expression of loss- and
      gain-of-function mutations, we can describe three types of Lk regulation. In the
      brain LHLK cells, both Sqz and Apterous (Ap) are required for LK expression, but
      surprisingly, high levels of either Sqz or Ap alone are sufficient to restore LK
      expression in these neurons. In the suboesophageal SELK cells, Sqz, but not Ap,
      is required for LK expression. In the abdominal ABLK neurons, inhibition of
      retrograde axonal transport reduces LK expression, and although sqz is
      dispensable for LK expression in these cells, it can induce ectopic leucokinergic
      ABLK-like cells when over-expressed. Thus, Sqz appears to be a regulatory factor
      for neuropeptidergic identity common to all leucokinergic cells, whose function
      in different cell types is regulated by cell-specific factors.

PMID- 17442545
TI  - [Medication administration errors in a pediatric intensive care unit].
AB  - The administration act, as each step of the drugs circuit, can lead to an adverse
      drug event potentially harmful for the patient. The aim of this study was to
      highlight the adverse drug events outcoming at the administration stage and to
      suggest improvement elements. Errors were identified in a retrospective manner.
      We compared the written prescriptions ("Prescription forms") with the
      administration registration ("Administration forms"). The differences observed
      between these two paper media were classified according to the errors types
      defined by the American Society of Hospital Pharmacists and by the American
      Society of Consultant Pharmacists. This study settled in the pediatric intensive
      care unit of a teaching hospital. We checked 1035 administrations lines: 180
      errors (17,4%) were detected, including 63 omissions, 44 infusion rate errors, 42
      administrations without prescription, 20 administration time errors, 7 dose
      errors, 2 drug form errors, 2 errors of other types, but no route of
      administration error. This method choice is debatable because without direct
      observation we could only compare what was noted to be administrated and not what
      was really administrated. We did not try to identify neither the causes nor the
      consequences of these errors on the patients. Following this study, several
      improvements have been set up: a new "Prescription form" (expecting the
      computerized prescription order entry) and reconstitution and dilution protocols
      for the most prescribed drugs.

PMID- 17442546
TI  - [Long lasting side effects of immunosuppressants in children].

PMID- 17442547
TI  - [Fryns syndrome. Report on 3 new cases].
AB  - BACKGROUND: Fryns syndrome is a lethal autosomal recessive syndrome which
      includes congenital diaphragmatic hernia (CDH), pulmonary hypoplasia, cranio
      facial manifestations including a coarse face, a cleft palate / lip and cloudy
      corneae, distal limb hypoplasia and internal malformations including central
      nervous system, cardiovascular, gastrointestinal, urogenital and skeletal
      anomalies. CASES REPORT: We report on 3 patients with Fryns syndrome in the
      french Indian Ocean islands (La Reunion and Mayotte islands). Pregnancies were
      complicated by polyhydramnios. All patients had coarse face, cloudy corneae,
      cleft lip / palate or high-arched palate, hypoplastic nails and
      brachytelephalangy. They died in the neonatal period. Two had CDH and 1 did not
      have a diaphragmatic involvement but a severe respiratory distress syndrome with
      refractory hypoxemia. Cytogenetic studies of blood lymphocytes and skin
      fibroblasts were normal. CONCLUSIONS: Fryns syndrome is the most common multiple
      congenital anomaly associated with CDH. The diagnosis is strongly suggested when
      CHD and brachytelephalangy are associated. Phenotypes with CDH similar to Fryns
      syndrome have been described with cytogenetic aberrations with G-banded
      chromosome analysis and submicroscopic chromosome deletions detected by high
      resolution karyotyping or array comparative genomic hybridization (CGH).
      Exclusion of chromosome aberrations (including isochromosome 12p in skin
      fibroblasts) is needed prior to making the diagnosis of Fryns syndrome. In
      sporadic cases, high resolution karyotyping or array CGH should be performed for
      correct diagnosis and genetic counselling.

PMID- 17442548
TI  - [Post licensure safety surveillance for Prevenar].
AB  - OBJECTIVE: The aim was to detect as soon as possible a rare but severe or
      unexpected adverse effect (AE) of Prevenar vaccine. A pharmacovigilance survey
      was required by the French drug agency (Afssaps) to the regional
      pharmacovigilance centre of Tours (France). METHOD: Two approaches were used. One
      based upon systematic reports and the other upon spontaneous reports. Only severe
      and /or unexpected AEs were recorded. RESULTS: During the 19 months of intensive
      follow up, 24 AEs (8.7 [5-12.7]/100000 vaccinations) reported by 349
      participating paediatricians have been analyzed. Prevenar was the only drug taken
      in 67% of children. AEs were severe (19 cases) or non severe but unexpected (5
      cases). AEs were fever above 39 degrees C (10 cases), cutaneous manifestations (6
      cases), neurologic manifestations (5 cases), diarrhoea-vomiting (2 cases), and
      purulent otitis media (1 case). During the 3.5 years of spontaneous reporting,
      130 AEs (6 [5-7]/100000 vaccinations) have been reported and analyzed. AEs were
      severe (107 cases) or non severe but unexpected (23 cases). AEs were mainly:
      fever above 39 degrees C (17 cases), cutaneous (39 cases), neurologic (34 cases)
      and haematological (3 cases) manifestations and diarrhoea-vomiting (5 cases). In
      3 children local AE limited the walk (5 cases). DISCUSSION: Our results are not
      far from north American data (VAERS) regarding incidence, kind of AEs and
      severity. Abnormal crying, members hypertonia and vascularitis not yet mentioned
      in Prevenar SPC need to be added. CONCLUSION: Regarding these new data, benefice
      risk balance of Prevenar vaccine remains favourable for active immunisation
      against invasive infections due to pneumococcus in children.

PMID- 17442549
TI  - [Announcing risks in paediatric oncology: ethical and relational aspects].

PMID- 17442550
TI  - [Allergic and pseudoallergic reactions to analgesics, antipyretics and non
      steroidal anti-inflammatory drugs].
AB  - Antalgics, antipyretics and non-steroidal anti-inflammatory drugs (NSAIDs) are
      widely used, but suspected allergic reactions to these drugs are rare, especially
      in children. Most frequent reactions are cutaneous (urticaria, angioedema) and
      respiratory (rhinitis, asthma). Other reactions (anaphylaxis or anaphylactoid
      reactions, potentially harmful toxidermias) are rare. In a few patients,
      reactions may result from a specific (allergic) hypersensitivity (HS), with
      positive responses in prick and intradermal tests (anaphylaxis, immediate
      urticaria and/or angioedema) and in intradermal and patch tests (non-immediate
      reactions). However, most reactions result from a non-specific (non-allergic) HS
      (intolerance), with a frequent cross-reactivity between the various families of
      antalgics, antipyretics and NSAIDs, including acetaminophen (paracetamol). Based
      on a convincing clinical history and/or positive responses in challenge tests,
      intolerance to antalgics, antipyretics and NSAIDs has been diagnosed in 13 to 50%
      of the patients with allergic-like reactions to these drugs. Risk factors for HS
      to antalgics, antipyretics and NSAIDs are a personal atopy and age. In our
      experience, 50% of the children with allergic-like reactions to antipyretics,
      antalgics and NSAIDs were diagnosed intolerant to these drugs. Risk was high in
      children reporting reactions to NSAIDs (aspirin, ibuprofen) and lower in children
      reporting reactions to paracetamol. All the children intolerant to paracetamol
      were also intolerant to NSAIDs. In contrast, most children with NSAID intolerance
      were tolerant to paracetamol. A personal history of atopy and a mean age >or= 8
      years were significant risk factors for intolerance to antalgics, antipyretics
      and NSAIDs.

PMID- 17442551
TI  - [When doors slam, fingers jam!].
AB  - AIM: Epidemiological analysis in a universitary paediatric emergency unit of
      children admitted after accidental injuries resulting from fingers crushed in a
      door. MATERIAL AND METHODS: Prospective, descriptive cohort study from September
      6th, 2004 to July 1st, 2005 included all children admitted for finger injuries
      crushed in a non-automatic door. EXCLUSIONS: included accidents due to automatic
      doors, toy's or refrigerator doors, families who refused to participate to the
      study or families who had left the waiting area before medical examination.
      Collected data were patient and family characteristics, accident characteristics
      and its management. RESULTS: Three hundred and forty children affected by 427
      digital lesions were included. The mean age was 5.5+/-3.8 years (range 4 months -
      15.5 years). Male/female ratio was equal to 1.2: 1. Fifty-eight percent of
      patients belonged to families composed of 3 or more siblings. Ninety-three per
      cent of families came to hospital within the first 2 hours after the accident
      (mean delay 99+/-162 min, median range 54 minutes). Location of the accident was:
      domestic (62%, at home (64%)), at school (17%). Locations within the home were:
      the bedroom (33%), bathroom and toilets (21%). An adult was present in 75% of
      cases and responsible for the trauma in 25% of accidents, another child in 44%.
      The finger or fingers were trapped on the hinge side in 57% of patients. No
      specific safeguard devices were used by 94% of families. Among victims, 20% had
      several crushed digits; left and right hand were injured with an equal frequency.
      The commonest involved digits were: the middle finger (29%), the ring finger
      (23%). The nail plate was damaged in 60% of digital lesions, associated with a
      wound (50%), a distal phalanx fracture (P3) (12%). Six children had a partial or
      complete amputation of P3, 2 children a lesion of the extensor tendon, 1 child
      had a rupture of the external lateral ligament. Three percent of children
      required an admission to the paediatric orthopaedic surgery unit. Post-traumatic
      pain was mainly limited to the first 48 h (64%). Early complications included: 16
      cases of infected injuries, 3 cases of pulpar necrosis. The total cost of
      hospital care was 71,500 euros, the average cost for hospitalised patient equal
      to 2100 euros and for ambulatory cases equal to 141 euros; the annual cost was
      estimated at 81,600 euros. CONCLUSION: Associated with potentially serious
      digital injuries, functional or inesthetic sequelae, this painful experience
      still remains too frequent in toddlers for a home accident that could be often
      prevented by the acquisition of specific protective doors devices and for a
      reasonable cost compared to the cost of hospital care.

PMID- 17442552
TI  - [Revelation of an acute lymphoblastic leukemia in the delivery room].
AB  - Acute leukemia is uncommon in neonates and has a much poorer prognosis than in
      older children. We report on a case of acute lymphoblastic leukemia observed in a
      neonate who had bleeding and hepatosplenomegaly at birth, which justified
      intensive care during the first postnatal week. Despite early appropriate
      treatment, the patient died at 7 months of age. We present here physical and
      laboratory findings, which indicate a grim prognosis. These criteria should be
      considered carefully in order to ensure a realistic information for the parents
      and appropriate decisions.

PMID- 17442553
TI  - [Diagnosis of hemolytic uremic syndrome].
AB  - Hemolytic uremic syndrome is a disease of nonimmune hemolytic anemia, low
      platelet count and renal impairment. In children below three years old, the
      disease is most commonly triggered by contaminated food and is the first cause of
      acute renal failure. Shiga-like toxin Escherichia coli (STEC) are responsible for
      the disease. Modalities of contamination, clinical course of bloody diarrhea and
      chronology of biological defects are described in this paper.

PMID- 17442554
TI  - [Sudden infant death syndrome and virtual autopsy: scalpel or mouse?].

PMID- 17442555
TI  - What are the gastrointestinal endoscopic requirements of a cancer centre?
AB  - AIMS: To describe the elective endoscopy requirements of a cancer centre.
      MATERIALS AND METHODS: A prospective register of all patients referred from a
      cancer centre to our unit over a period of 1 year was maintained. Emergency
      procedures out of hours were not included. RESULTS: The Endoscopic Unit at the
      Chelsea and Westminster Hospital provides a service to the local population of
      southwest London and the Fulham Road branch of the Royal Marsden Hospital.
      Between 1 January and 31 December 2003, 3720 new National Health Service patients
      with cancer were seen at the Royal Marsden Hospital; 1423 of these patients were
      seen at the Fulham Road branch. In the same period, the Endoscopy Unit at the
      Chelsea and Westminster Hospital investigated 5270 patients. Of these, 426
      patients (8.1%) were referred from the Royal Marsden Hospital. In total, these
      patients underwent 491 procedures. Two hundred and fifty-three patients were men,
      with a median age of 65 years (range 22-100), and 173 were women, with a median
      age of 58 years (range 18-100). The diagnostic procedures carried out included
      colonoscopy (n=125), upper gastrointestinal endoscopy (n=136), flexible
      sigmoidoscopy (n=90), endoscopic ultrasound (n=24), anorectal physiology
      measurement (n=5) and endoscopic retrograde cholangio-pancreatography (ERCP)
      (n=1). Therapeutic procedures included ERCP (biliary stents/sphincterotomy/stone
      extraction) (n=38), placement of percutaneous endoscopic gastrostomy (n=29),
      balloon dilatation of oesophageal strictures (n=25), oesophageal, gastric,
      duodenal or colonic stent insertion or laser therapy (n=16), naso-jejunal tube
      insertion (n=1) and banding of oesophageal varices (n=1). All patients were
      treated as day cases. Four patients were admitted for observation after their
      investigation. All others were discharged home or back to the Royal Marsden
      Hospital. CONCLUSIONS: Cancer centres increasingly require diagnostic, palliative
      and therapeutic endoscopic support as part of the acute and follow-up management
      of patients. Many procedures are urgent. This study suggests that a significant
      number of patients being managed in a cancer centre will require endoscopic
      intervention and the range of procedures, equipment and skills required is wide.

PMID- 17442556
TI  - Safety evaluation of BacoMind in healthy volunteers: a phase I study.
AB  - BacoMind is an enriched phytochemical composition of Bacopa monniera (B.
      monniera), a common medicinal plant used in the traditional systems of medicine
      as a memory-enhancing agent. BacoMind was standardized with reference to
      bioactive compounds and was evaluated for short-term safety and tolerability in
      healthy adult volunteers. The study plan employed randomized, open label, dose
      escalation design. Each of 23 participants were orally given one single capsule
      of BacoMind daily for 30 days, i.e., 300 mg for first 15 days and 450 mg for next
      15 days. Detailed examination of clinical, hematological, biochemical and
      electrocardiographic parameters done in pre and post-treatment periods did not
      indicate any untoward effects in any of the treated volunteers. Mild adverse
      events related to gastrointestinal system were observed in the trial, which
      subsided spontaneously. BacoMind was found to meet the safety criteria at the
      dose administered for the given duration of trial period in healthy adult
      volunteers.

PMID- 17442557
TI  - Apoptosis induced by the lymphocyte effector molecule perforin.
AB  - Recent progress has been made in discovering structure/function relationships of
      the cytotoxic lymphocyte pore-forming protein - perforin - and its role in immune
      regulation. Long recognized as a key component of the granule exocytosis
      mechanism of lymphocyte-mediated apoptosis and in host defence against a variety
      of pathogens and tumors, more recent attention has focused upon mutations of the
      perforin gene in some patients with hemophagocytic lymphohistiocytosis. This
      clinical picture has prompted further work to uncover the molecular structure of
      perforin and to define its precise role in immune regulation and immunopathology.

PMID- 17442558
TI  - Natural killer cells: from CD3(-)NKp46(+) to post-genomics meta-analyses.
AB  - The original definition of NK cells was based on their 'natural' cytolytic
      response against tumor cells and virus-infected cells in the absence of specific
      immunization. However, the term 'natural killer' reflects neither the
      education/maturation requirements before NK cells can kill nor the entirety of
      their biological functions. In light of new functional assays, genetic models and
      genomics analysis, we propose a more accurate definition of NK cells. This
      definition includes the phenotypical identification of NK cells as CD3(-)NKp46(+)
      cells across mammalian species. In general, this attempt to redefine NK cells
      also highlights the need to update the operational definition of cell types in
      the post-genomic area.

PMID- 17442559
TI  - Lymphocyte effector functions: armed for destruction?

PMID- 17442561
TI  - Residential proximity fine particles related to allergic sensitisation and asthma
      in primary school children.
AB  - BACKGROUND: Fine particulate matter has been linked to allergies by experimental
      and epidemiological data having used aggregated data or concentrations provided
      by fixed-site monitoring stations, which may have led to misclassification of
      individual exposure to air pollution. METHODS: A semi-individual design was
      employed to relate individual data on asthma and allergy of 5338 school children
      (10.4 +/- 0.7 years) attending 108 randomly chosen schools in 6 French cities to
      the concentrations of PM2.5 (fine particles with aerodynamic diameter 2.5 microm)
      assessed in proximity of their homes. Children underwent a medical visit
      including skin prick test (SPT) to common allergens, exercise-induced bronchial
      (EIB) reactivity and skin examination for flexural dermatitis. Their parents
      filled in a standardised health questionnaire. RESULTS: After adjustment for
      confounders and NO2 as a potential modifier, the odds of suffering from EIB and
      flexural dermatitis at the period of the survey, past year atopic asthma and SPT
      positivity to indoor allergens were significantly increased in residential
      settings with PM2.5 concentrations exceeding 10 microg/m3 (WHO air quality limit
      values). The relationships were strengthened in long-term residents (current
      address for at least 8 years). CONCLUSIONS: Findings support the hypothesis that
      changes in allergy prevalence observed in recent decades might be partly related
      to interactions between traffic-related air pollution and allergens. Further
      longitudinal investigations are needed to corroborate such results.

PMID- 17442562
TI  - Potentials for the prevention of municipal solid waste.
AB  - Waste prevention has been assigned the highest priority under European waste
      management law. However, the initiatives which have been taken so far have not
      reduced the regular annual increase in total waste arising across Europe. The
      purpose of this paper is to quantify and analyze in depth the prevention
      potential for selected case studies (advertising material, beverage packaging,
      diapers, food waste, waste from events). Only such measures are considered, which
      do not require a reduction of consumption. The prevention potentials for
      household waste in theory are exemplified for the city of Vienna, also with a
      view to barriers that may reduce the achievable prevention potential. The results
      show that the prevention potentials for the analyzed individual measures can
      reach an order of magnitude of some 10% of the relevant waste stream (e.g.,
      advertising material, beverage packaging), or rather 1-3% of municipal solid
      waste. The prevention potentials appear to be relatively small in relation to the
      total municipal waste quantities. Methodological shortcomings, such as the
      missing availability of basic data, make it difficult to exactly estimate the
      impact of waste prevention measures on waste quantities, which is only one of the
      effects of waste prevention among other ecological, social and economic aspects.

PMID- 17442563
TI  - A novel multi-array immunoassay device for tumor markers based on insert-plug
      model of piezoelectric immunosensor.
AB  - A novel multi-array immunoassay device based on the insert-plug model of
      piezoelectric (Pz) immunosensor fabricated with the screw clamp apparatus has
      been developed for quantitative detection of tumor markers such as alpha
      fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate specific antigen
      (PSA), and carcinoma antigen 125 (CA125) in serum, in which single immunosensor
      can oscillate independently with the frequency stability of +/-1 Hz (hertz) in
      air phase and +/-2 Hz in liquid phase. These response characteristics of Pz tumor
      marker multi-array immunoassay device such as time-cost, reproducibility and
      specificity, etc. were also investigated, respectively. The detection range for
      AFP, CEA, PSA and CA125 obtained by multi-array Pz immunosensor were 20-640
      ng/ml, 1.5-30 microg/ml, 1.5-40 ng/ml and 5-150 IU/ml, respectively, with the
      coefficient of variance (CV) less than 5% and no cross-reactivates with other
      tumor markers in serum were observed. Application of the multi-array immunosensor
      to clinical samples demonstrated that results were in good agreement with
      chemiluminescence immunoassay (CLIA). Moreover, the multi-array Pz immunosensor
      could be regenerated to be reused for three cycles without appreciable loss of
      response activity. Therefore, the proposed multi-array immunoassay device based
      on Pz immunosensor provides a rapid, sensitive, specific, reusable, convenient
      and reliable alternative for the detection of tumor markers in clinical
      laboratory.

PMID- 17442564
TI  - Expression of metastin and a G-protein-coupled receptor (AXOR12) in epithelial
      ovarian cancer.
AB  - BACKGROUND: Metastin, a product of the KiSS-1 gene, is a ligand for a G-protein
      coupled receptor (AXOR12) and is a strong suppressant of metastasis. The aim of
      this study was to evaluate whether metastin and AXOR12 gene expressions affect
      prognosis of patients with epithelial ovarian cancer. METHODS: The expression
      levels of metastin, AXOR12 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)
      gene expression were analysed by the real-time quantitative reverse transcription
      polymerase chain reaction in 76 epithelial ovarian cancer surgical specimens.
      Their expression (metastin/GAPDH and AXOR12/GAPDH ratios) was correlated with the
      clinical findings. Furthermore, cellular distribution of metastin and AXOR12 mRNA
      was examined by in situ hybridisation on tissue sections. RESULTS: The median and
      range of mRNA expression for metastin and AXOR12 were 0.047 and 0.01-13.57, and
      4.00 and 0.011-135.13, respectively. Patients were dichotomised into two groups
      having low and high expressions by using the median value as the cutoff. A good
      agreement was noticed between metastin and AXOR12 gene expression levels (kappa
      coefficient; 0.74). The presence of residual tumour following resection was
      negatively associated with metastin (P=0.0084) and AXOR12 (P=0.0148) gene
      expressions indicating an association of low expression of these genes in more
      aggressive, and advanced tumours. By univariate Cox regression analysis, the
      prognosis of the patients with low AXOR12 gene expression was significantly worse
      than those with high AXOR12 gene expression (P=0.030). The combination of
      metastin and AXOR12 gene expression level was also significantly associated with
      the prognosis (P=0.049). Transcripts for both metastin and AXOR12 were detected
      in the epithelial ovarian carcinoma cells. CONCLUSIONS: These results present a
      new insight into the understanding of the biological behaviour of epithelial
      ovarian cancer. Metastin/AXOR12 signalling may suppress the invasive phenotype of
      epithelial ovarian cancer.

PMID- 17442565
TI  - Geldanamycin derivatives and neuroprotective effect on cultured P19-derived
      neurons.
AB  - Geldanamycin (1), an antifungal and anticancer ansamycin, was reported as a
      neurotrophic and neuroprotective substance against antineoplastic drugs,
      paclitaxel, vincristine, and cisplatin, on cultured dorsal root ganglion neurons
      from chick embryos. In this study, 1 in a large quantity, together with a known
      17-O-demethylgeldanamycin (2), and a new 17-O-demethylgeldanamycin hydroquinone
      (3) were obtained from a mangrove Streptomyces sp. A series of O-alkyl and N
      alkyl derivatives of 1 were prepared by modification of C-17 and/or C-19 on the
      quinone ring and were evaluated for in vitro activity against P19-derived
      neurons. Compound 1 and 19-O-methylgeldanamycin (7) at a very low dose (1nM)
      enhanced survival and neurite outgrowth of P19-derived neurons and prevented
      neurotoxicity of paclitaxel and vinblastine. Compound 7, possessing the lowest
      cytotoxicity and neurotoxicity, is serving as the most promising candidate in
      neurodegenerative therapy against neurotoxic anticancer drugs.

PMID- 17442566
TI  - A cell-permeable inhibitor and activity-based probe for the caspase-like activity
      of the proteasome.
AB  - The ubiquitin-proteasome pathway degrades the majority of proteins in mammalian
      cells and plays an essential role in the generation of antigenic peptides
      presented by major histocompatibility class I molecules. Proteasome inhibitors
      are of great interest as research tools and drug candidates. Most work on
      proteasome inhibitors has focused on the inhibition of the chymotryptic-like
      (beta5) sites; little attention has been paid to the inhibition of two other
      types of active sites, the trypsin-like (beta2) and the caspase-like (beta1). We
      report here the development of the first cell-permeable and highly selective
      inhibitors (4 and 5) of the proteasome's caspase-like site. The selectivity of
      the compounds is directly and unambiguously established by Staudinger-Bertozzi
      labeling of proteasome subunits covalently modified with azide-functionalized
      inhibitor 5. This labeling reveals that the caspase-like site of the
      immunoproteasome (beta1i) is a preferred target of this compound. These compounds
      can be used as tools to study roles of beta1 and beta1i sites in generation of
      specific antigenic peptides and their potential role as co-targets of anti-cancer
      drugs.

PMID- 17442567
TI  - Piperidine amides as 11beta-hydroxysteroid dehydrogenase type 1 inhibitors.
AB  - A series of piperidine amide inhibitors of human 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) were identified via modifications of the HTS
      hit compound 1. The synthesis, in vitro biological evaluation, and structure
      activity relationship of these compounds are presented.

PMID- 17442568
TI  - Benzimidazo[1,2-c][1,2,3]thiadiazole-7-sulfonamides as inhibitors of carbonic
      anhydrase.
AB  - A series of benzimidazo[1,2-c][1,2,3]thiadiazole-7-sulfonamides were synthesized
      and their binding to two carbonic anhydrase isozymes measured by isothermal
      titration calorimetry (ITC). Human carbonic anhydrase I (hCAI) and bovine
      carbonic anhydrase II (bCAII) bound the inhibitors with observed association
      constants in the range from 1.1 x 10(6) to 2.6 x 10(7) M(-1).

PMID- 17442569
TI  - CRACM1, CRACM2, and CRACM3 are store-operated Ca2+ channels with distinct
      functional properties.
AB  - STIM1 in the endoplasmic reticulum and CRACM1 in the plasma membrane are
      essential molecular components for controlling the store-operated CRAC current.
      CRACM1 proteins multimerize and bind STIM1, and the combined overexpression of
      STIM1 and CRACM1 reconstitutes amplified CRAC currents. Mutations in CRACM1
      determine the selectivity of CRAC currents, demonstrating that CRACM1 forms the
      CRAC channel's ion-selective pore, but the CRACM1 homologs CRACM2 and CRACM3 are
      less well characterized. Here, we show that both CRACM2 and CRACM3, when
      overexpressed in HEK293 cells stably expressing STIM1, potentiate I(CRAC) to
      current amplitudes 15-20 times larger than native I(CRAC). A nonconducting
      mutation of CRACM1 (E106Q) acts as a dominant negative for all three CRACM
      homologs, suggesting that they can form heteromultimeric channel complexes. All
      three CRACM homologs exhibit distinct properties in terms of selectivity for
      Ca(2+) and Na(+), differential pharmacological effects in response to 2-APB, and
      strikingly different feedback regulation by intracellular Ca(2+). Each of the
      CRAC channel proteins' specific functional features and the potential
      heteromerization provide for flexibility in shaping Ca(2+) signals, and their
      characteristic biophysical and pharmacological properties will aid in identifying
      CRAC-channel species in native cells that express them.

PMID- 17442570
TI  - Identification of nuclear dicing bodies containing proteins for microRNA
      biogenesis in living Arabidopsis plants.
AB  - MicroRNAs (miRNAs) are important for regulating gene expression in muticellular
      organisms. MiRNA processing is a two-step process. In animal cells, the first
      step is nuclear and the second step cytoplasmic, whereas in plant cells, both
      steps occur in the nucleus via the enzyme Dicer-like1 (DCL1) and other proteins
      including the zinc-finger-domain protein Serrate (SE) and a double-stranded RNA
      (dsRNA) binding-domain protein, Hyponastic Leaves1 (HYL1). Furthermore, plant
      miRNAs are methylated by Hua Enhancer (HEN1) at their 3' ends and loaded onto
      Argonaute1 (AGO1). However, little is known about the cellular basis of miRNA
      biogenesis. Using live-cell imaging, we show here that DCL1 and HYL1 colocalize
      in discrete nuclear bodies in addition to being present in a low-level diffuse
      nucleoplasmic distribution. These bodies, which we refer to as nuclear dicing
      bodies (D-bodies), differ from Cajal bodies. A mutated DCL1 with impaired
      function in miRNA processing fails to target to D-bodies, and an introduced
      primary (pri)-miRNA transcript is recruited to D-bodies. Furthermore, bimolecular
      fluorescence complementation (BiFC) shows that DCL1, HYL1, and SE interact in D
      bodies. On the basis of these data, we propose that D-bodies are crucial for
      orchestrating pri-miRNA processing and/or storage/assembly of miRNA-processing
      complexes in the nuclei of plant cells.

PMID- 17442571
TI  - Tpt1 activates transcription of oct4 and nanog in transplanted somatic nuclei.
AB  - Nuclear transfer to eggs or oocytes provides a potential route for cell
      replacement therapies because oocytes directly reprogram transplanted mammalian
      somatic-cell nuclei such that they have an embryo-like pattern of gene
      expression. This includes a large increase in the mRNA level of the stem-cell
      marker gene oct4. We have developed a novel procedure to identify new proteins
      that greatly increase the level of oct4 mRNA upon nuclear transfer. We have
      isolated Xenopus oocyte proteins that bind to the regulatory region of the mouse
      oct4 gene and identified these by mass spectrometry. The proteins include the
      retinoic-acid-receptor gamma, a known repressor of oct4 transcription, and Tpt1,
      a cancer-associated factor. The depletion of transcripts of retinoic-acid
      receptor gamma from oocytes increases oct4 and nanog transcription as expected,
      and depletion of tpt1 transcripts in oocytes reduces oct4 and nanog transcription
      in injected HeLa nuclei. An elevation of tpt1 transcripts in oocytes results in
      an earlier activation of oct4 transcription. Therefore, we identify a novel role
      for tpt1 in activating pluripotency genes upon nuclear transfer. Our results help
      to elucidate the mechanism by which somatic-cell nuclei are reprogrammed to have
      an embryo-like pattern of gene expression.

PMID- 17442572
TI  - Virulence is positively selected by transmission success between mammalian hosts.
AB  - Virulence, defined as damage to the host, is a trait of pathogens that
      evolutionary theory suggests benefits the pathogen in the "struggle for
      existence". Pathogens employ virulence mechanisms that contribute to disease.
      Central to the evolution of virulence of the infectious agents causing an array
      of bacterial disease is the evolutionary acquisition of type III secretion, a
      macromolecular complex that creates a syringe-like apparatus extending from the
      bacterial cytosol to the eukaryotic cytosol and delivers secreted bacterial
      virulence factors (effectors) into host cells. In this work, we quantify the
      contribution of virulence determinants to the evolutionary success of a pathogen.
      Using a natural pathogen of mice, we show that virulence factors provide a
      selective advantage by enhancing transmission between hosts. Virulence factors
      that have a major contribution to disease were absolutely required for
      transmission of the pathogen to naive hosts. Virulence-factor mutants with more
      subtle defects in pathogenesis had quantifiable roles in the time required to
      transmit the pathogen between mice. Virulence-factor mutants were also found to
      lose in competition with wild-type bacteria when iteratively transmitted from
      infected to uninfected mice. These results directly demonstrate that virulence is
      selected via the fitness advantage it provides to the host-to-host cycle of
      pathogenic species.

PMID- 17442573
TI  - Shedding light on Merlin's wizardry.
AB  - Inactivation of the tumor suppressor Merlin, encoded by the NF2
      (Neurofibromatosis type 2) gene, contributes to malignant conversion in many cell
      types. Merlin is an Ezrin-Radixin-Moesin protein and localizes underneath the
      plasma membrane at cell-cell junctions and other actin-rich sites. Recent studies
      indicate that Merlin mediates contact inhibition of proliferation by blocking
      recruitment of Rac to the plasma membrane. In mitogen-stimulated cells, p21
      activated kinase phosphorylates Ser518 in the C-terminus of Merlin, inactivating
      the growth suppressive function of the protein. Furthermore, the myosin
      phosphatase MYPT1-PP1delta, has been identified as a direct activator of Merlin
      and its inhibition has been linked to malignant transformation. Finally, studies
      in the fruit fly Drosophila melanogaster have revealed that Merlin functions
      together with the band 4.1 protein Expanded to promote [corrected] the
      endocytosis of many signaling receptors, limiting [corrected] their accumulation
      at the plasma membrane, and to activate [corrected] the Hippo signaling pathway.
      Here, we review these recent findings and their relevance to the tumor suppressor
      function of Merlin.

PMID- 17442574
TI  - Age-related changes of visual contribution in posture control.
AB  - INTRODUCTION: Numerous studies highlighted that the role of vision in posture
      control increased with aging. However, these previous works only considered
      simple tasks consisting in "stand as still as possible" and people aged over 65
      years. The present study aimed to determine changes in the role of vision in
      posture control during two different visual tasks for people aged between 40 and
      60 years. METHOD: A stabilometric platform was used to register the effect of a
      modification of the visual environment on the postural behaviour. Subjects stood
      upright on thick foam and their attention was focused on the visual task. Two
      visual tasks were considered: a recognition task and a Rapid Serial Visual
      Presentation task. Seventy-four subjects (44 between 21 and 31 years and 31
      between 44 and 60 years) took part in the study, performing both visual tasks one
      after the other. RESULTS: Results showed that 44-60 years old subjects were more
      unstable than young subjects, especially in the dark. The postural behaviour of
      the former was also more dependent on the properties of the visual environment.
      Visual contribution in postural control did not only depend on age but also on
      task constraints. DISCUSSION: The present study showed that the increased role of
      vision with age in posture control, classically investigated for people aged over
      60 years, could also be highlighted in a 44-60 years old population. Furthermore,
      the study showed that 44-60 years old subjects' posture was more sensitive to the
      attentional constraints of the task than young subjects.

PMID- 17442575
TI  - Decoding the mannitol enigma in filamentous fungi.
AB  - Mannitol is a 6-carbon polyol that is among the most abundant biochemical
      compounds in the biosphere. Mannitol has been ascribed a multitude of roles in
      filamentous fungi including carbohydrate storage, reservoir of reducing power,
      stress tolerance and spore dislodgement and/or dispersal. The advancement of
      genetic manipulation techniques in filamentous fungi has rapidly accelerated our
      understanding of the roles and metabolism of mannitol. The targeted deletion of
      genes encoding proteins of mannitol metabolism in several fungi, including
      phytopathogens, has proven that the metabolism of mannitol does not exist as a
      cycle and that many of the postulated roles are unsupported. These recent studies
      have provided a much needed focus on this mysterious metabolite and make this a
      fitting time to review the roles and metabolism of mannitol in filamentous fungi.

PMID- 17442576
TI  - Synthesis of new S-derivatives of clubbed triazolyl thiazole as anti
      Mycobacterium tuberculosis agents.
AB  - In the present study, a series of N-{4-[(4-amino-5-sulfanyl-4H-1,2,4-triazol-3
      yl)methyl]-1,3-thiazol-2-yl}-2-substituted-amide (1a-d) derivatives were
      synthesized in good yields and characterized by IR, 1H NMR, mass spectral and
      elemental analyses. The compounds were evaluated for their preliminary in vitro
      antibacterial activity against Staphylococcus aureus, Escherichia coli,
      Pseudomonas aeruginosa and Salmonella typhosa and then were screened for
      antitubercular activity against Mycobacterium tuberculosis H37 Rv strain by broth
      microdilution assay method. The antibacterial data of the tested compounds
      indicated that most of the synthesized compounds showed better activity against
      bacteria compared to reference drugs. The in vitro antitubercular activity
      reports of tested compounds against M. tuberculosis strain H37 Rv showed moderate
      to better activity.

PMID- 17442577
TI  - Antimicrobial and cytotoxic activity of agelasine and agelasimine analogs.
AB  - Agelasine and agelasimine derivatives with substantially less complicated
      terpenoid side chains compared to the naturally occurring compounds have been
      synthesized and their ability to inhibit growth of microorganisms and cancer
      cells has been studied. Compounds with excellent activity against cancer cell
      lines (MIC ca. 1 microM for the most potent compounds), including a drug
      resistant renal cell line, have been identified. Most compounds studied also
      exhibited broad spectrum antimicrobial activity including activity against
      Mycobacterium tuberculosis.

PMID- 17442578
TI  - Tritium labelling of several potent fluorinated antipsychotic drugs at high
      specific activity.
AB  - Methods are presented to synthesize and characterize [methylene-3H] haloperidol 2
      and [N-methyl-3H]trifluoperazine 6.

PMID- 17442580
TI  - Visual complications of Stickler syndrome in paediatric patients with Robin
      sequence.
AB  - BACKGROUND: The most frequent diagnosis in patients with syndromic Pierre Robin
      sequence is Stickler syndrome, which may be complicated by congenital high myopia
      and substantial risk of retinal detachment. However, cases of Stickler syndrome
      with probable visual complications are rarely identified among this group of
      patients by members of the cleft team. This study was designed to determine the
      prevalence of Stickler syndrome among the author's group of patients with Robin
      sequence, and to investigate the visual outcome among paediatric patients with
      Robin sequence and Stickler syndrome. MATERIAL AND METHODS: Eight children (six
      male and two female) with Stickler syndrome and Robin sequence were referred to
      be followed up every 6 months in the Ophthalmologic Department because of high
      myopia at less than 10 years of age. Three patients came from the author's study
      group and five were referred by other cleft surgeons. They were examined with
      repeat ophthalmic and indirect fundus examinations including cycloplegic
      refraction, and slit lamp biomicroscope examinations. Laser photocoagulation (2
      cases) treatment for retinal degeneration or operation (3 cases) for retinal
      detachment was performed once evidence of significant ophthalmologic finding was
      noted. RESULTS: Of the 91 cases of newborns with isolated cleft palate treated by
      the first author, eight patients had Robin sequence, and among these, three had
      Stickler syndrome. The prevalence of Stickler syndrome among this subgroup of
      patients was 37.5% (3/8). Among these three patients and the additional five
      referred by other cleft surgeons, the average spherical equivalents of the first
      cycloplegic refraction for the 16 eyes was -12.39+/-2.72 diopter (D) (range -8.75
      to -18.5D). Of the eight patients, five did not need any therapy, two children
      had retinal degeneration in the left eye and retinal detachment in the right eye
      while one child had retinal detachment in the right eye only. Laser
      photocoagulation was performed in the two left eyes with retinal degeneration and
      was successful. Surgery was performed on the three eyes with retinal detachment,
      one was successful while two failed and the patients developed total blindness at
      ages four and six respectively. Out of these three children with retinal
      complications, only one child remained free of visual deterioration in both eyes
      during the follow-up period. CONCLUSION: Early identification of Stickler
      syndrome in children with Robin sequence by cleft surgeons is necessary to insure
      early referral to an ophthalmologist for detection of myopia, monitoring for
      retinal detachment, and prevention of visual complications.

PMID- 17442579
TI  - Is functional state of spinal microglia involved in the anti-allodynic and anti
      hyperalgesic effects of electroacupuncture in rat model of monoarthritis?
AB  - Spinal microglia play a key role for creating exaggerated pain following tissues
      inflammation or injury. Electroacupuncture (EA) can effectively control the
      exaggerated pain both in humans with inflammatory disease and animals with
      experimental inflammatory pain. However, little is known about the relationship
      between spinal glial activation and EA analgesia. Using immunohistochemistry, RT
      PCR analysis, and behavioral testing, the present study demonstrated that (1)
      Unilateral intra-articular injection of CFA produced a robust microglial
      activation and the up-regulation of the tumor necrosis factor (TNF)-alpha,
      interleukin (IL-1beta), and IL-6 mRNA levels in the spinal cord; (2) Repeated
      intrathecal (i.t.) injection of minocycline (100 microg), a microglial inhibitor,
      or EA stimulation of ipsilateral "Huantiao"(GB30) and "Yanglingquan" (GB34)
      acupoints significantly suppressed CFA-induced nociceptive behavioral
      hypersensitivity and spinal microglial activation; (3) Combination of EA with
      minocycline significantly enhanced the inhibitory effects of EA on allodynia and
      hyperalgesia. For the first time, these data provide direct evidence for the
      involvement of spinal microglial functional state in anti-nociception of EA.
      Thus, anti-neuroinflammatory effect of EA might be considered as one of the
      mechanisms of its anti-arthritic pain effects, and thereby a multidisciplinary
      integrated approach to treating symptoms related to arthritis might be raised.

PMID- 17442581
TI  - Does sleeve lobectomy concomitant with or without pulmonary artery reconstruction
      (double sleeve) have favorable results for non-small cell lung cancer compared
      with pneumonectomy? A meta-analysis.
AB  - It has been reported that sleeve lobectomy (SL) concomitant with or without
      pulmonary artery reconstruction (PAR) might be an alternative procedure for
      pneumonectomy (PN) in non-small cell lung cancer (NSCLC). The aim of this study
      was to assess whether SL or PN offers a low morbidity and mortality and better
      long-term survival. We performed a meta-analysis of studies published in English
      between 1996 and 2006 to comprehensively compare the postoperative mortality,
      morbidity, locoregional recurrences, and time-to-event outcomes of SL and PN in
      NSCLC, and reviewed the recent literatures on PAR in the corresponding period as
      well. Twelve studies met the defined criteria including a total of 2984 subjects,
      and five studies for PAR. The odds ratio for postoperative mortality (SL vs PN)
      was 0.65 (95% confidence interval (CI): 0.42-1.01), 1.01 (95% CI: 0.70-1.44) for
      postoperative complications, and 0.91 (95% CI: 0.45-1.82) for locoregional
      recurrences. The weighted mean operative mortality for PAR was 3.3%, and 32.4%
      for complications. The estimated combined hazard ratio for overall survival in 10
      studies was 0.70 (95% CI: 0.62-0.79) in favor of SL group. The median overall
      survival was 60 months for the SL group, 26 months for the PN group, and 30
      months for PAR group. Survival difference in patients with pN0 or pN1 at 1 year
      demonstrated a pooled risk difference (SL vs PN) of 0.03 (95% CI: -0.08-0.13),
      0.13 (95% CI: 0.00-0.25) in patients with pN2 at 1 year, 0.21 (95% CI: 0.07-0.36)
      in patients with pN0 or pN1 at 5 years, and 0.06 (95% CI: -0.10-0.21) in patients
      with pN2 at 5 years. Our results suggests that SL with or without PAR can be
      accomplished safely in selected patients without increasing the morbidity and
      mortality as compared to PN, that SL even with PAR offers better long-term
      survival than does PN, and that a more radical operation such as PN is not a more
      appropriate procedure, even in higher stage tumors.

PMID- 17442582
TI  - Endovascular management of a descending thoracic mycotic aneurysm: mid-term
      follow-up.
AB  - Open surgical repair of mycotic aneurysm is associated with a high surgical
      morbidity and mortality. Endovascualr graft management of thoracic aortic
      aneurysm has been associated with a less surgical risk. The role of endovascular
      graft repair of mycotic aneurysm remains controversial since graft material
      remains in contact with possible infected tissue. We report the marked thrombosis
      and marked regression of a thoracic mycotic aneurysm with an endovascular graft
      at mid-term follow-up.

PMID- 17442583
TI  - Is adhesive paper-tape closure of video assisted thoracoscopic port-sites safe?
AB  - Video assisted thoracoscopic surgery (VATS) is used in lung surgery for
      diagnostic, staging, curative and palliative purposes. The port-sites are usually
      sutured with dissolvable sutures. The use of adhesive paper-tape for port-site
      closure was assessed by a prospective randomised double-blind control trial
      comparing sutured to adhesive paper-tape closure. The following outcomes were
      assessed: incidence of clinically significant pneumothorax, wound healing using
      the ASEPSIS score, patient's comfort (pain score using a visual analog score),
      the time difference between the two techniques of wound closure and cost savings.
      Thirty patients were recruited in each group. No clinically significant
      pneumothoraces occurred in either group. There were no significant differences
      between the two groups in terms of immediate post-operative pain scores, wound
      cosmesis and wound complications. It was quicker to close the wound with adhesive
      paper-tape with a mean time of closure per unit length of wound of 9.3 and
      2.2s/mm for the groups, respectively. The cost for wound closure (per patient)
      was $0.8 for the adhesive paper-tape group and $4.00 for the sutures.

PMID- 17442584
TI  - Effectiveness of gabapentin in the treatment of chronic post-thoracotomy pain.
AB  - BACKGROUND: Chronic post-thoracotomy pain (CPTP) consists of different types of
      pain. Some characteristics of CPTP are the same as those of recognized
      neuropathic pain syndromes. OBJECTIVE: We aimed to determine the safety and
      efficacy of gabapentin (GP) in comparison to naproxen sodium (NS) in patients
      with CPTP. METHODS: Forty consecutive patients with CPTP after
      posterolateral/lateral thoracotomy were prospectively evaluated. Twenty patients
      were given GP and another 20 were given NS treatment. Visual Analogue Scale (VAS)
      and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) scorings were
      performed pretreatment (day 0) and on the 15th, 30th, 45th and 60th days. Adverse
      events were questioned. The mean ages were 45.7+/-14.9 and 49.8+/-15.2 years and
      the mean durations of pain were 3.8+/-0.9 and 3.8+/-1.1 months, respectively.
      RESULTS: The mean pretreatment VAS scores (VAS0) were 6.4+/-0.6 and 6.8+/-0.6,
      the mean pretreatment LANSS scores (LANSS0) were 18.85+/-1.6 and 20.75+/-2.6 in
      GP and NS groups, respectively (p>0.05). Minor adverse events which did not
      mandate discontinuation of treatment were observed in seven patients (35%) in the
      GP and in four patients (20%) in the NS group. The number of patients with a VAS
      score <5 at the latest follow-up (VAS60 < 5) was 17 (85%) and 3 (15%) in GP and
      NS groups, respectively (p<0.001). Seventeen patients (85%) in the GP and 0
      patients (0%) in the NS group had a LANSS score <12 at the latest follow-up.
      CONCLUSION: Gabapentin is safe and effective in the treatment of CPTP with
      minimal side effects and a high patient compliance. These results should be
      supported with multidisciplinary studies with larger sample sizes and longer
      follow-ups.

PMID- 17442585
TI  - Androgen receptor function in folliculogenesis and its clinical implication in
      premature ovarian failure.
AB  - The action of estrogen in the female reproductive organs is well known in terms
      of the expression pattern and gene regulation of the estrogen receptor (ER). The
      significance of ERs in female reproduction is undisputed. The role of the
      androgen receptor (AR) is less clear. Clinical hyperandrogenism, a typical
      feature of polycystic ovary syndrome (PCOS), highlights pathological androgen
      production by the ovary. By contrast, the physiological impact of androgen action
      in female reproductive organs remains elusive. Androgens affect folliculogenesis
      in a variety of experimental approaches and ARs are expressed in developing
      follicles. Recent observations have discovered that inactivation of ARs in female
      mice results in premature ovarian failure (POF), indicating that normal
      folliculogenesis requires AR-mediated androgen action. Moreover, these results
      imply that POF might be caused by impairment of AR-mediated androgen action.

PMID- 17442586
TI  - Localization and differential interaction of R7 RGS proteins with their membrane
      anchors R7BP and R9AP in neurons of vertebrate retina.
AB  - G protein signaling in the retina is crucially regulated by the R7 family of
      regulators of G protein signaling (RGS) proteins, which act to stimulate the rate
      of G protein inactivation. Recent findings indicate that R7 RGS proteins form
      complexes with two newly identified membrane anchors: RGS9 Anchor Protein (R9AP)
      and R7 Binding Protein (R7BP), which play essential roles in modulating the
      expression and localization of R7 RGS proteins. Here we demonstrate that the four
      R7 RGS proteins: RGS6, RGS7, RGS9 and RGS11 differentially associate with two
      membrane anchors. R9AP was found to form complexes with RGS9 and RGS11 which were
      substantially enriched in the photoreceptors. In contrast, complexes of R7BP with
      R7 RGS proteins were predominantly localized to the synaptic projections of
      retina neurons, suggesting their involvement in regulation of synaptic
      transmission between retina neurons. Furthermore, studies of knockout mice
      revealed that R9AP is necessary for the expression of only RGS9 but not for RGS6,
      7 or 11. Together these data suggest that R7 RGS proteins in the retina are
      present as macromolecular complexes with their membrane anchors that could
      differentially regulate their function in various retina neurons.

PMID- 17442587
TI  - Effects of salmonid fish viruses on Mx gene expression and resistance to single
      or dual viral infections.
AB  - We examined the ability of several fish viruses to induce protection against
      homologous or heterologous viruses in single or double infections, and assessed
      whether such protection is correlated with innate immunity or expression of the
      Mx gene. Monolayers of BF2 cells pre-treated with supernatants of brown trout
      (Salmo trutta L.) macrophage cultures that had been stimulated with either
      polyinosinic polycytidylic acid (poly I:C) or viruses, such as infectious
      pancreatic necrosis virus (IPNV), infectious haematopoietic necrosis virus (IHNV)
      or a mixture of the two, showed varying degrees of protection against viral
      infections. The virus showing the strongest induction was IPNV, and the antiviral
      activity against IHNV was also high: around 6 log(10) reduction of virus yield.
      Consequently, the IPNV-IHNV co-infection yield was also reduced by varying
      amounts. In vivo, the cumulative mortality observed in the IPNV-IHNV co-infected
      fish was always less than that in those with a single infection. Stimulation with
      poly I:C for 7 days significantly reduced cumulative mortality in single-infected
      fish, but not in the double-infected, in which the IPNV was the only virus
      isolated from moribund animals. By RT-PCR, Mx was expressed in all the organ
      samples tested (kidney, liver and spleen) from virus-stimulated fish at 1, 2 and
      3 days. By qRT-PCR the extent and timing of Mx expression was shown to differ in
      the poly I:C and the single or dual viral infections. The highest increase in Mx
      expression (21.6-fold above basal levels) occurred (after 24 h) in fish infected
      with the IHNV, and expression remained high until day 7. Mx expression in fish
      infected with IPNV peaked later, at 2 days post infection, and also remained high
      until day 7. The dual infection with IPNV-IHNV induced high Mx expression on day
      1, which peaked on day 2 and remained high until day 7. These results indicate
      that activation of the immune system could explain the interference and loss of
      IHNV in the IPNV-IHNV co-infections.

PMID- 17442588
TI  - Tissue-specific expression and regulation of the haemolymph clottable protein of
      tiger shrimp (Penaeus monodon).
AB  - The clottable protein (CP) involved in Penaeus monodon haemolymph coagulation has
      previously been characterized and cloned. Polyclonal antibodies against purified
      CP were also prepared from rabbit serum. By Western blot analyses, we showed
      occurrence of CP in the shrimp central nervous system, gill, and lymphoid organ.
      Results of RT-PCR further indicated that the central nervous system, gill, and
      lymphoid organ transcribed more CP, heart and hepatopancreas transcribed less,
      while the haemocytes and the muscle did not. We further analyzed the CP
      distribution within shrimp lymphoid organ by immunohistochemical method, CP was
      found to localise in stromal cells of lymphoid organ rather than in the
      developing haemocytes. In addition, concentrations and regulation of the plasma
      CP under normal and artificially traumatic conditions were studied with rocket
      immunoelectrophoresis. The average plasma CP concentration in normal intermolt
      shrimps was elevated from 3 mg ml(-1) to above 12 mg ml(-1) after successive
      blood-withdrawing for a week. The production and secretion of CP apparently were
      increased more than 4 folds to compensate its loss. Our result also suggested
      that the shrimp sinus gland endocrine system is not directly required for the
      expression and up-regulation of CP.

PMID- 17442589
TI  - mRNA expression patterns of the BPI/LBP molecule in the Atlantic cod (Gadus
      morhua L.).
AB  - Bactericidal/permeability-increasing protein (BPI) and lipopolysaccharide-binding
      protein (LBP) are important components of the mammalian innate defence system
      against Gram-negative infections. cDNA encoding a protein related to mammalian
      BPI and LBP have been cloned from several teleosts including the Atlantic cod
      (Gadus morhua L.). Using real-time PCR an increase in cod BPI/LBP expression in
      whole blood and peritoneal cells was demonstrated one, two and four days after
      intraperitoneal injection of inactivated Vibrio anguillarum. Although
      constitutively produced in the head kidney, a moderate rise of BPI/LBP mRNA
      production was seen on day two in this organ. After seven days the BPI/LBP mRNA
      levels at the three locations examined were almost back to normal. In situ
      hybridisation demonstrated a leucocytic localisation and morphology of the
      BPI/LBP expressing cells in various tissues. A combination of in situ
      hybridisation and peroxidase staining of head kidney leucocytes showed that the
      BPI/LBP producing cells are peroxidase positive and possible neutrophil like
      cells. The results suggest that the cod BPI/LBP is important in the first-line
      defence against bacterial infections and has a function more related to the
      mammalian BPI molecule than the LBP counterpart.

PMID- 17442590
TI  - Bacterial lipopolysaccharides induce genes involved in the innate immune response
      in embryos of the zebrafish (Danio rerio).
AB  - The innate immune response in fish represents an early, rapid defence against
      pathogens. Environmental contaminants could disturb this defence and negatively
      influence the ability to protect against infection. However, analysis of immune
      modulation has not yet been included in testing strategies for environmental risk
      assessment of chemicals. In order to establish an efficient, small scale test
      system, the ability to induce the innate immune response by bacterial
      lipopolysaccharides in zebrafish embryos was investigated. The level of
      expression of various genes involved in inflammation was used as the endpoint. We
      could show that immersion of embryos in LPS induced the gene expression of two
      key pro-inflammatory cytokines, tumor necrosis factor alpha and interleukin 1
      beta in 32 h old zebrafish embryos. The gene induction required the removal of
      the chorion prior to lipopolysaccharide exposure.

PMID- 17442591
TI  - Two ferritin subunits from disk abalone (Haliotis discus discus): cloning,
      characterization and expression analysis.
AB  - Ferritin plays a key role in cellular iron metabolism, which includes iron
      storage and detoxification. From disk abalone, Haliotis discus discus, the cDNA
      that encodes the two ferritin subunits abalone ferritin subunit 1 (Abf1) and
      abalone ferritin subunit 2 (Abf2) were cloned. The complete cDNA coding sequences
      for Abf1 and Abf2 contained 621 and 549 bp, encoding for 207 and 183 amino acid
      residues, respectively. The H. discus discus Abf2 subunit contained a highly
      conserved motif for the ferroxidase center, which consists of seven residues of a
      typical vertebrate heavy-chain ferritin with a typical stem-loop structure. Abf2
      mRNA contains a 27 bp iron-responsive element (IRE) in the 5'UTR position. This
      IRE exhibited 96% similarity with pearl and Pacific oyster and 67% similarity
      with human H type IREs. However, the Abf1 subunit had neither ferroxidase center
      residues nor the IRE motif sequence; instead, it contained iron-binding region
      signature 2 (IBRS) residues. Recombinant Abf1 and Abf2 proteins were purified and
      the respective sizes were about 24 and 21 kDa. Abf1 and Abf2 exhibited iron
      chelating activity 44.2% and 22.0%, respectively, at protein concentration of 6
      microg/ml. Analysis of tissue-specific expression by RT-PCR revealed that Abf1
      and Abf2 ferritin mRNAs were expressed in various abalone tissues, such as gill,
      mantle, gonad, foot and digestive tract in a wide distribution profile, but Abf2
      expression was more prominent than Abf1.

PMID- 17442592
TI  - Anisotropy in the visual cortex investigated by neuronavigated transcranial
      magnetic stimulation.
AB  - Responses to transcranial magnetic stimulation (TMS) of the motor cortex depend
      on the direction of the induced current with an optimum perpendicular to the
      orientation of the precentral gyrus. Little is known about anisotropy in other
      cortical regions. We measured phosphene thresholds in the visual cortex using a
      frameless neuronavigation system. Comparing horizontal and vertical current
      orientation as well as monophasic and biphasic pulses in 7 subjects, we found
      lower thresholds with biphasic pulses and a tendency for lower thresholds with
      horizontal currents. When varying current directions in steps of 45 degrees
      centered on a hot spot over the occipital cortex, in 10 out of 12 measurements
      optimal current orientation ran perpendicular to the underlying gyrus (mean
      deviation 14.6 degrees). Optimal current orientation was determined as the
      orientation of the second eigenvector from the covariance matrix of the
      stimulation sites that had been shifted along the respective current direction by
      the amount of the measured threshold. Individual cortical architecture was
      obtained by segmentation of a 3d anatomical MR scan, with large interindividual
      differences among the orientations of the stimulated gyrus. As with the motor
      system, the optimum threshold with biphasic pulses was flipped about 180 degrees
      compared to the optimum with monophasic pulses (p<.02) throughout subjects,
      suggesting both similar anisotropic properties of networks in the visual and
      motor cortices and the existence of anisotropic behaviour in any cortical region.
      As a consequence, optimal TMS application should always take into account the
      individual orientation of the gyrus to be stimulated.

PMID- 17442593
TI  - Amygdala responses to nonlinguistic emotional vocalizations.
AB  - Whereas there is ample evidence for a role of the amygdala in the processing of
      visual emotional stimuli, particularly those with negative value, discrepant
      results have been reported regarding amygdala responses to emotional auditory
      stimuli. The present study used event-related functional magnetic resonance
      imaging to investigate cerebral activity underlying processing of emotional
      nonlinguistic vocalizations, with a particular focus on neural changes in the
      amygdala. Fourteen healthy volunteers were scanned while performing a gender
      identification task. Stimuli, previously validated on emotional valence,
      consisted of positive (happiness and sexual pleasure) and negative (sadness and
      fear) vocalizations, as well as emotionally neutral sounds (e.g., coughs).
      Results revealed bilateral amygdala activation in response to all emotional
      vocalizations when compared to neutral stimuli. These findings suggest that the
      generally accepted involvement of the amygdala in the perception of emotional
      visual stimuli, such as facial expressions, also applies to stimuli within the
      auditory modality. Importantly, this amygdala response was observed for both
      positive and negative emotional vocalizations.

PMID- 17442594
TI  - Plasticity of the corticospinal tract in early blindness revealed by quantitative
      analysis of fractional anisotropy based on diffusion tensor tractography.
AB  - Early visual deprivation may induce plastic changes, not only in the visual
      system, but also in the remaining sensory systems, secondary to altered
      experience in these spared modalities. Most of previous studies were focused on
      the plasticity of cortical areas of sensory modalities, but little attention was
      paid to the plasticity of motor system and white matter fiber tracts. Our purpose
      is to investigate the plasticity of the corticospinal tract (CST) in early
      blindness by tract-based quantitative analysis of fractional anisotropy (FA).
      Diffusion tensor imaging was performed in 17 early blind and 17 gender- and age
      matched sighted subjects. The entire CST of each subject was reconstructed and
      the average FA of the tract was analyzed. To validate the results derived from
      the entire CST, we further analyzed a segment of the CST between the lowest slice
      of the cerebral peduncle and the uppermost slice of the lateral ventricle, in
      which the fibers are coherently arranged and the anatomical correspondence of the
      CST across subjects is established. On comparison with matched sighted
      participants, the average FA of the CST was significantly increased in the early
      blind men, but not in the early blind women. In conclusion, the plasticity of the
      CST is present in the early blind men, which might be related to the changes of
      motor experience during critical developmental period of the CST. This study also
      supports the perspective that experience-dependent plasticity occurs not only in
      the cortical areas but also in the white matter fiber tracts.

PMID- 17442595
TI  - Different response of articular chondrocyte subpopulations to surface motion.
AB  - OBJECTIVE: To investigate the effect of surface motion on the gene expression of
      proteoglycan 4 (PRG4), hyaluronan synthases (HAS1, HAS2) and on the hyaluronan
      (HA) and proteoglycan 4 (PRG4) release of chondrocytes from different zones of
      bovine articular cartilage. DESIGN: Superficial zone, deep zone, full thickness,
      and superficial/deep 1:1 mixed chondrocytes were seeded into 3D polyurethane
      scaffolds and stimulated using our bioreactor that approximates kinematics and
      surface motion characteristics of natural joints. One hour of surface motion
      superimposed on cyclic compression was applied twice a day over 3 consecutive
      days. Scaffolds were cut into top and bottom sections and analyzed for gene
      expression of PRG4, HAS1, and HAS2. RESULTS: Depending on the cell population,
      the gene expression levels increased within 8 days of culture in unloaded
      scaffolds, with a stronger increase in the top compared to the bottom sections.
      Mechanical loading further enhanced the messenger RNA (mRNA) levels in all cell
      types, with most pronounced up-regulations observed for the PRG4 expression in
      deep zone and the HAS2 expression in superficial zone cells. The effect of the
      biochemical and biomechanical environment appeared to be additive, resulting in
      highest mRNA levels in the top sections of loaded constructs. Bioreactor
      stimulation also enhanced the HA release in all cell populations. Full thickness
      chondrocytes experienced the greatest effect on HAS1 mRNA expression and HA
      release, indicating that the interaction between cell populations may promote HA
      synthesis compared to subpopulations alone. CONCLUSIONS: Reciprocating sliding
      can be an efficient tool for generating tissue-engineered constructs from various
      chondrocyte populations by providing a functional cartilage-synovial interface.

PMID- 17442596
TI  - Oxygen consumption of equine articular chondrocytes: Influence of applied oxygen
      tension and glucose concentration during culture.
AB  - We investigated the oxygen (O(2)) uptake of equine articular chondrocytes to
      assess their reactions to anoxia/re-oxygenation. They were cultured under 5% or
      21% gas phase O(2) and at glucose concentrations of 0, 1.0 or 4.5g/L in the
      culture medium (n=3). Afterwards, the O(2) consumption rate of the chondrocytes
      was monitored (oxymetry) before and after an anoxia period of 25min. The glucose
      consumption and lactate release were measured at the end of the re-oxygenation
      period. The chondrocytes showed a minimal O(2) consumption rate, which was hardly
      changed by anoxia. Independently from the O(2) tension, glucose uptake by the
      cells was about 30% of the available culture medium glucose, thus higher for
      cells at 4.5g/L glucose (n=3). Lactate release was also independent from O(2)
      tension, but lower for cells at 4.5g/L glucose (n=3). Our observations indicated
      that O(2) consumption by equine chondrocytes was very low despite a functional
      mitochondrial respiratory chain, and nearly insensitive to anoxia/re-oxygenation.
      But the chondrocytes metabolism was modified by an excess of O(2) and glucose.

PMID- 17442597
TI  - The transcription factor GABP is a critical regulator of B lymphocyte
      development.
AB  - GA binding protein (GABP) is a ubiquitously expressed Ets-family transcription
      factor that critically regulates the expression of the interleukin-7 receptor
      alpha chain (IL-7Ralpha) in T cells, whereas it is dispensable for IL-7Ralpha
      expression in fetal liver B cells. Here we showed that deficiency of GABPalpha,
      the DNA-binding subunit of GABP, resulted in profoundly defective B cell
      development and a compromised humoral immune response, in addition to thymic
      developmental defects. Furthermore, the expression of Pax5 and Pax5 target genes
      such as Cd79a was greatly diminished in GABPalpha-deficient B cell progenitors,
      pro-B, and mature B cells. GABP could bind to the regulatory regions of Pax5 and
      Cd79a in vivo. Thus, GABP is a key regulator of B cell development, maturation,
      and function.

PMID- 17442598
TI  - Complete identification of E-selectin ligands on neutrophils reveals distinct
      functions of PSGL-1, ESL-1, and CD44.
AB  - The selectins and their ligands are required for leukocyte extravasation during
      inflammation. Several glycoproteins have been suggested to bind to E-selectin in
      vitro, but the complete identification of its physiological ligands has remained
      elusive. Here, we showed that E-selectin ligand-1 (ESL-1), P-selectin
      glycoprotein ligand-1 (PSGL-1), and CD44 encompassed all endothelial-selectin
      ligand activity on neutrophils by using gene- and RNA-targeted loss of function.
      PSGL-1 played a major role in the initial leukocyte capture, whereas ESL-1 was
      critical for converting initial tethers into steady slow rolling. CD44 controlled
      rolling velocity and mediated E-selectin-dependent redistribution of PSGL-1 and L
      selectin to a major pole on slowly rolling leukocytes through p38 signaling.
      These results suggest distinct and dynamic contributions of these three
      glycoproteins in selectin-mediated neutrophil adhesion and signaling.

PMID- 17442600
TI  - cDNA microarray analysis of the expression profiles of Trichophyton rubrum in
      response to novel synthetic fatty acid synthase inhibitor PHS11A.
AB  - Trichophyton rubrum (T. rubrum) is a major pathogen responsible for
      dermatophytosis. Because of potential relapse of disease with current antifungal
      therapy protocols, there is a need for additional and/or alternative antifungal
      agents for the treatment of disease caused by T. rubrum. We synthesized a potent
      fungal fatty acid synthase inhibitor, PHS11A, based on the structure of fungal
      fatty acid synthase. The antifungal activities of PHS11A were tested against 38
      clinical isolates of T. rubrum and compared with those of ketoconazole and
      terbinafine, the MIC(50) and MIC(90) of PHS11A on the isolates were 2 and 4
      microg/ml, respectively. We evaluated the transcriptional response of T. rubrum
      hyphae exposed to PHS11A using 11,232-spot cDNA microarrays. PHS11A exposure
      increased transcription of fatty acid synthases (FASs) genes FAS1 and FAS2.
      PHS11A also affected transcription of some genes involved in lipid metabolism,
      cAMP and MAPK pathways, and multidrug resistance. Quantitative real-time PCR was
      performed for selected genes to verify the microarray results.

PMID- 17442601
TI  - Long-term use of Levetiracetam in patients with severe childhood-onset epilepsy.
AB  - OBJECTIVE: To assess the efficacy and tolerability of Levetiracetam (LEV) in
      children and adolescents with refractory epilepsy with a special interest in the
      long-term retention rate. METHOD: One hundred and twenty-nine patients (83 male,
      46 female; mean age 10.6 years/range: 6 months-39 years 9 months) were included
      in a prospective, open-label, add-on trial of LEV for up to 3 years. All patients
      had severe forms of epilepsy starting before the age of 10 often accompanied by
      mental retardation. Primary outcome measures were changes in seizure frequency
      after 6 months on the medication with LEV, with initial responders (>50% seizure
      reduction). Further objective was the retention rate of LEV therapy after 3 years
      defined as percentage of patients still taking LEV. RESULTS: Thirty-five patients
      (27.1%) were initial responders of which 5 became seizure free. The average
      maximum LEV dosage was 39.8 mg/kg/day (range: 6-70 mg/kg/day) with no difference
      responders vs. no responders. The retention rate for responders after 3 years was
      22.5%. The rate of side effects was 39.8% in all patients, with the most frequent
      side effects being fatigue (12.5%), aggressiveness (7.8%) and gastrointestinal
      disorders (13.3%). CONCLUSIONS: Our study in patients with refractory epilepsy
      suggests that our initial responders were very likely to be still taking LEV
      after 3 years. We therefore consider treatment with LEV in this special group of
      patients with refractory epilepsy a promising therapeutic option, because of its
      favourable tolerance profile, the option of fast titration and the absence of
      drug interactions.

PMID- 17442602
TI  - Effects of airway anesthesia on dyspnea and ventilatory response to intravenous
      injection of adenosine in healthy human subjects.
AB  - We have recently shown that intravenous injection of adenosine causes dyspnea and
      hyperventilation in man, and we suggested that stimulation of vagal C-fibers in
      the airways and lungs is involved. To test this hypothesis further, the present
      study was performed in healthy subjects (n=12; age 32.4+/-10.2 yrs, 7 females) to
      determine if the effect of adenosine could be attenuated by blocking the airway
      sensory receptors by inhalation of aerosolized lidocaine, a local anesthetic. In
      each subject, the effects of intravenous injection of adenosine (10mg) on
      dyspneic sensation, minute ventilation, airway resistance and heart rate were
      measured after the subject inhaled lidocaine or placebo aerosol on two separate
      days. After a latency of approximately 20s, adenosine injection evoked a distinct
      dyspneic sensation, increase in minute ventilation (VE), and transient
      bradycardia followed by tachycardia in all subjects. The increase in VE resulted
      primarily from a significant increase in tidal volume. The intensity of adenosine
      induced dyspnea was markedly reduced after the lidocaine pretreatment compared to
      placebo. In a sharp contrast, the VE and heart rate responses to adenosine were
      not affected by lidocaine. These results lend further support to our previous
      studies indicating that the origin of the dyspnogenic action of intravenous
      adenosine is most likely vagal bronchopulmonary C-fiber sensory nerves.

PMID- 17442599
TI  - The metabolic consequences of sleep deprivation.
AB  - The prevalence of diabetes and obesity is increasing at an alarming rate
      worldwide, and the causes of this pandemic are not fully understood. Chronic
      sleep curtailment is a behavior that has developed over the past 2-3 decades.
      Laboratory and epidemiological studies suggest that sleep loss may play a role in
      the increased prevalence of diabetes and/or obesity. Current data suggest the
      relationship between sleep restriction, weight gain and diabetes risk may involve
      at least three pathways: (1) alterations in glucose metabolism; (2) upregulation
      of appetite; and (3) decreased energy expenditure. The present article reviews
      the current evidence in support of these three mechanisms that might link short
      sleep and increased obesity and diabetes risk.

PMID- 17442603
TI  - Renal clearance of absorbed intact GFP in the frog and rat intestine.
AB  - Intestine absorption of intact green fluorescent protein (GFP) and its following
      accumulation in the renal proximal tubule cells after its intragastric
      administration have been established by confocal microscopy in the rat and frog.
      Reabsorbed GFP was revealed in the endosomes and lysosomes of the proximal tubule
      cells by the methods of GFP photooxidation and immunofluorescent microscopy. The
      GFP intestine absorption rate and GFP accumulation in the kidney were
      significantly higher in the frog than in the rat. No specific fluorescence was
      revealed in the liver and colon cells after the GFP intragastric administration.
      The data obtained indicate the ability of the small intestine in the frog and rat
      to absorb intact proteins and an important role of the kidney in exogenous
      protein metabolism.

PMID- 17442604
TI  - Autofluorescence as a tool to study mucus secretion in Eisenia foetida.
AB  - Autofluorescence in living cells is due to the presence of endogenous substances
      that emit fluorescence upon excitation by incidental light. A type of
      fluorescence, bioluminescence, has been suggested to be linked to mucus secretion
      in earthworms; however, the origin and the physiological function of this
      fluorescence are not clear. The aims of this work were to describe
      autofluorescence in the earthworm Eisenia foetida by SEM, CLSM, and fluorescence
      microscopy and to examine the possible mechanism of mucus secretion by video
      microscopy. Earthworms were stimulated either chemically or electrically to
      induce the secretion of yellow mucus, which was subsequently studied by video
      microscopy. Mucus was released from the body wall and near the mouth. This
      phenomenon was associated with autofluorescence and involved at least four
      distinct stages: release of vesicles, formation of granules, muscular
      contraction, and organization of strands. The fluorescent molecules were stored
      in vesicles bound to the membranes. These vesicles were intact when shed from the
      body. The vesicles were stable but also changed to a granular material or formed
      strands. Video analyses demonstrated that secretion was dependent on the type of
      stimulus.

PMID- 17442605
TI  - Dermaseptins from Phyllomedusa oreades and Phyllomedusa distincta: Secondary
      structure, antimicrobial activity, and mammalian cell toxicity.
AB  - The present study reports the structural characteristics, the biological
      activities, and preliminary clinical investigations of three synthetic members of
      the dermaseptin family of antimicrobial peptides. The three peptides showed
      similar tendencies to form alpha-helical structures in non-polar media. The
      antimicrobial activity towards bacteria and fungi was determined in the
      micromolar concentration and the peptides did not influenced peritoneal cells
      viability. One of the peptides was intravenously administered in mice at
      concentrations similar to those of antibiotics employed in bacterial/fungal
      infections and it did not cause any detectable changes in cells and tissues.

PMID- 17442606
TI  - [Do family events play a part in male infertility?].
AB  - The object of this study is the family history of a set of infertile men, through
      a filiation event grid. This study examines the genealogical tree established
      during the genetic session, which precedes an ICSI procedure, and applies this
      filiation grid to a sample of 30 men met in the ART department and to a reference
      group of 30 fertile men met in a maternity hospital after the birth of their
      child. The results show statistical differences in the filiation events of both
      populations. We can therefore assume that difficulties in the past generations
      may play a part in some cases of male infertility.

PMID- 17442607
TI  - [Is there a role for X-ray pelvimetry in the twenty-first century?].

PMID- 17442608
TI  - [Tissue resistance: what about tension-free?].

PMID- 17442609
TI  - Prevalence of cervical dystonia and spasmodic torticollis in the United States
      general population.
AB  - PURPOSE: To examine the prevalence of cervical dystonia (CD) in the US
      population. METHOD: A survey consisting of relevant demographic and CD-related
      questions was e-mailed to 2 million people selected from the Shopper's Voice
      database. RESULTS: Across a census-weighted sample, 0.280% of 60,062 respondents
      (79% female, 92% Caucasian) reported a diagnosis of CD and 0.170% reported a
      diagnosis of ST, indicating possible prevalence of 0.390% of either/both
      diagnoses. Less than half (42.7%) of those who reported either diagnosis were
      receiving treatment. CONCLUSIONS: CD is potentially under-diagnosed and under
      treated; approaches to increase awareness of CD and its treatments are needed.

PMID- 17442610
TI  - Restless legs syndrome and periodic limb movements after ischemic stroke in the
      right lenticulostriate region.
AB  - We report the first instance of restless legs syndrome (RLS) associated with
      periodic limb movements (PLM) and disruption of sleep architecture occurring in a
      patient following ischemic infarction in the right lenticulostriate region.
      Recently, a role for the basal ganglia-brainstem system in the control of motor
      behaviors and in the regulation of awake-sleep states has been proposed. The
      purported roles of these structures may be relevant in explaining the occurrence
      of the RLS in our patient. The discrete brain localization observed in this
      patient may be a clue to a better understanding of the pathophysiology of RLS and
      PLM.

PMID- 17442611
TI  - The new frontier in cancer research: deciphering cancer epigenetics.
AB  - Cancer has long been known to be a disease caused by alterations in the genetic
      blueprint of cells. In the past decade it has become apparent that epigenetic
      alterations also underlie the etiology of cancer. Since epigenetic changes may be
      more facile to reverse than genetic lesions, much research has been invested in
      their characterization. Success has indeed been booked in the clinic with drugs
      that erase DNA methylation imprints or that target histone post-translational
      modifications such as lysine acetylation. However, the actual consequences of
      current epigenetic pharmacological intervention protocols are still poorly
      characterized and may be rather pleiotropic in nature. The challenge we face is
      therefore to define the cellular enzymes responsible for epigenetic modifications
      at given genes under specific conditions, so as to develop pharmacological agents
      that target tumorigenic epigenetic lesions while eliciting minimal unwanted side
      effects. Application of genome-wide analytical tools has begun to provide spatio
      temporally resolved data that will be crucial to achieve this goal. Finally, the
      molecular mode of action of epigenetic drugs may be more intricate than initially
      thought, involving more than DNA and histones, since it has been reported that
      transcription (co)factors are themselves also targeted by histone modifying
      enzymes.

PMID- 17442612
TI  - Fruit ripening mutants yield insights into ripening control.
AB  - Fruit ripening is a developmental process that is exclusive to plants whereby
      mature seed-bearing organs undergo physiological and metabolic changes that
      promote seed dispersal. Molecular investigations into ripening control mechanisms
      have been aided by the recent cloning of tomato ripening genes that were
      previously known only through mutation. Advances in the genomics of tomato have
      provided genetic and molecular tools that have facilitated the positional and
      candidate-gene-based cloning of several key ripening genes. These discoveries
      have created new inroads into understanding of the primary ripening control
      mechanisms, including transcription factors such as those encoded by the RIPENING
      INHIBITOR (RIN) MADS-box and COLOURLESS NON-RIPENING (CNR) SPB-box genes, which
      are necessary for the progression of virtually all ripening processes. They have
      also facilitated the elucidation of downstream signal transduction components
      that impact the hormonal and environmental stimuli that coordinate and modulate
      ripening phenotypes.

PMID- 17442613
TI  - Spectrophotometric determination of H(2)-receptor antagonists via their oxidation
      with cerium(IV).
AB  - A simple, accurate and sensitive spectrophotometric method has been developed and
      validated for determination of H(2)-receptor antagonists: cimetidine, famotidine,
      nizatidine and ranitidine hydrochloride. The method was based on the oxidation of
      these drugs with cerium(IV) in presence of perchloric acid and subsequent
      measurement of the excess Ce(IV) by its reaction with p-dimethylaminobenzaldehyde
      to give a red colored product (lambda(max) at 464nm). The decrease in the
      absorption intensity of the colored product (DeltaA), due to the presence of the
      drug was correlated with its concentration in the sample solution. Different
      variables affecting the reaction were carefully studied and optimized. Under the
      optimum conditions, linear relationships with good correlation coefficients
      (0.9990-0.9994) were found between DeltaA values and the concentrations of the
      drugs in a concentration range of 1-20microgml(-1). The assay limits of detection
      and quantitation were 0.18-0.60 and 0.54-1.53microgml(-1), respectively. The
      method was validated, in terms of accuracy, precision, ruggedness and robustness;
      the results were satisfactory. The proposed method was successfully applied to
      the determination of the investigated drugs in pure and pharmaceutical dosage
      forms (recovery was 98.3-102.6+/-0.57-1.90%) without interference from the common
      excipients. The results obtained by the proposed method were comparable with
      those obtained by the official methods.

PMID- 17442614
TI  - HPV seminal shedding among men seeking fertility evaluation in Abidjan, Ivory
      Coast.
AB  - BACKGROUND: Little is known about the semen shedding of human papillomaviruses
      (HPV) in African men. OBJECTIVES: To detect and identify HPV types in semen
      samples from men seeking fertility evaluation in Abidjan, Ivory Cost. STUDY
      DESIGN: Sixty-three semen samples were tested by PCR using consensus primers and
      HPV types were determined by PCR product sequencing or by line probe assay (LiPA)
      when sequencing was inconclusive. RESULTS: A total of 19 HPV isolates belonging
      to 11 HPV types were identified in semen samples from 18 (28.6%) men. Ten (55.5%)
      of the HPV-positive men shed oncogenic HPV types. An association of borderline
      significance (P=0.06) was observed between HPV semen shedding and a lower sperm
      count. CONCLUSION: HPV shedding in semen is common in African men. The
      relationship between HPV semen shedding and sperm quality merits to be further
      investigated.

PMID- 17442615
TI  - Selection of a virus strain resistant to entecavir in a nucleoside-naive patient
      with hepatitis B of genotype H.

PMID- 17442616
TI  - Class B type I scavenger receptor is responsible for the high affinity
      cholesterol binding activity of intestinal brush border membrane vesicles.
AB  - Recent studies have documented the importance of Niemann-Pick C1-like 1 protein
      (NPC1L1), a putative physiological target of the drug ezetimibe, in mediating
      intestinal cholesterol absorption. However, whether NPC1L1 is the high affinity
      cholesterol binding protein on intestinal brush border membranes is still
      controversial. In this study, brush border membrane vesicles (BBMV) from wild
      type and NPC1L1-/- mice were isolated and assayed for micellar cholesterol
      binding in the presence or absence of ezetimibe. Results confirmed the loss of
      the high affinity component of cholesterol binding when wild type BBMV
      preparations were incubated with antiserum against the class B type 1 scavenger
      receptor (SR-BI) in the reaction mixture similar to previous studies.
      Subsequently, second order binding of cholesterol was observed with BBMV from
      wild type and NPC1L1-/- mice. The inclusion of ezetimibe in these in vitro
      reaction assays resulted in the loss of the high affinity component of
      cholesterol interaction. Surprisingly, BBMVs from NPC1L1-/- mice maintained
      active binding of cholesterol. These results documented that SR-BI, not NPC1L1,
      is the major protein responsible for the initial high affinity cholesterol ligand
      binding process in the cholesterol absorption pathway. Additionally, ezetimibe
      may inhibit BBM cholesterol binding through targets such as SR-BI in addition to
      its inhibition of NPC1L1.

PMID- 17442617
TI  - Pro-inflammatory action of LDL(-) on mononuclear cells is counteracted by
      increased IL10 production.
AB  - OBJECTIVE: LDL(-) is a minor LDL subfraction that induces inflammatory factor
      release by endothelial cells. Since LDL(-) is present in plasma, its interaction
      with leucocytes, a cell type involved in atherosclerosis phenomena, is feasible;
      therefore, the aim of the current study was to evaluate LDL(-) effect on
      lymphocytes and monocytes isolated from human plasma. METHODS AND RESULTS:
      Mononuclear cells were incubated with LDL(+) and LDL(-) and expression and
      release of several inflammatory mediators were analyzed by protein membrane
      assay, ELISA and real-time RT-PCR. LDL(-) induced a significantly increased
      production versus LDL(+) in MCP1, GRObeta, GROgamma, IL6, IL8 and IL10 in
      monocytes as well as in lymphocytes. These induced molecules are inflammatory,
      except for IL10 which is considered an anti-inflammatory cytokine. Therefore, the
      role of IL10 was evaluated in experiments where exogenous IL10 or antibodies anti
      IL10 or anti-IL10 receptor were added. IL10 addition diminished the release of
      the other factors induced by LDL(-) near to basal production both at protein and
      RNA level. In contrast, the antibody anti-IL10 increased inflammatory cytokine
      release around two-fold, whereas the antibody anti-IL10 receptor produced a lower
      effect. CONCLUSIONS: LDL(-) promoted inflammatory cytokine production in
      leucocytes; however, it also induced IL10 that minimized this effect. Therefore,
      IL10 developed a significant role in counteracting the LDL(-) inflammatory
      action.

PMID- 17442618
TI  - Management of retrosternal goitre with superior vena cava obstruction.
AB  - Acute respiratory and cardiovascular decompensation secondary to retrosternal
      goitre is uncommon but life threatening. We report our experience of successful
      surgical management of a patient who presented acute enlargement of the
      mediastinal component of retrosternal goitre, which resulted in tracheal and vena
      cava compression.

PMID- 17442619
TI  - Prosthesis-patient mismatch is associated with higher operative mortality
      following aortic valve replacement.
AB  - BACKGROUND: Prosthesis-patient mismatch (PPM) occurs when the valve prosthesis
      implanted at surgery is too small in relation to patient's body size, causing
      high transvalvular gradients. We investigated if severe PPM is related to early
      morbidity and mortality after aortic valve replacement (AVR). METHODS: We
      analysed prospectively collected data of 701 consecutive patients undergoing AVR
      between June 2001 and February 2006 at two Australian public hospitals. The
      indexed valve effective orifice area (IEOA) was estimated for each valve
      prosthesis implanted. PPM was defined as <or=0.65 cm2 m(-2). PPM was correlated
      with operative mortality, stroke, prolonged ventilation, new renal failure,
      prolonged intensive care stay, prolonged hospital stay and readmission to
      hospital within 30 days by univariate and multivariate methods. RESULTS: PPM was
      present in 6.6% of patients. Overall operative mortality was 4.1%. Isolated AVR
      was performed in only 38.4% of patients. For patients with PPM, the univariate
      and multivariate odds ratio for mortality were 5.2 (P=0.002) and 6.1 (P=0.006),
      respectively. The other multivariate predictors of mortality were age, pre
      operative serum creatinine, emergency status, pulmonary artery pressure and
      bypass time. PPM was not associated with stroke, prolonged ventilation, new renal
      failure, prolonged intensive care or hospital stay, or readmission within 30
      days. CONCLUSION: PPM was associated with increased operative mortality. PPM
      should be avoided where possible as it may reduce operative mortality following
      AVR.

PMID- 17442621
TI  - Nanotechnology platforms and physiological challenges for cancer therapeutics.
AB  - Nanotechnology is considered to be an emerging, disruptive technology that will
      have significant impact in all industrial sectors and across-the-board
      applications in cancer research. There has been tremendous investment in this
      area and an explosion of research and development efforts in recent years,
      particularly in the area of cancer research. At the National Institutes of
      Health, nanomedicine is one of the priority areas under its Roadmap Initiatives.
      Moreover, in 2005 the National Cancer Institute alone committed $144.3 million
      over 5 years for its Alliance for Nanotechnology in Cancer program. Much research
      and development is progressing in the areas of cancer diagnostics, devices,
      biosensors, and microfluidics, but this review will focus on therapeutics.
      Current nanotechnology platforms for cancer therapeutics encompass a vast array
      of nanomaterials and nanodevices. This review will focus on six of the most
      prominent and most widely studied: nanoshells, carbon nanotubes, dendrimers,
      quantum dots, superparamagnetic nanoparticles, and liposomes. All of these
      nanotechnology platforms can be multifunctional, so they are frequently touted as
      "smart" or "intelligent." This review will discuss the shared approaches in the
      design and development of these nanotechnology platforms that bestow such
      characteristics to the nanoparticles. Finally, the review will raise awareness of
      the physiological challenges for the application of these therapeutic
      nanotechnologies, in light of some recent advances in our understanding of tumor
      biology.

PMID- 17442622
TI  - How do family practitioners perceive surgery for the morbidly obese?
AB  - BACKGROUND: Little is known about the level of knowledge and comfort with
      bariatric surgery among family practice physicians. METHODS: Surveys were sent to
      all family practitioners in Connecticut querying the practice type and knowledge
      of bariatric surgery. The results were analyzed for the prevalence of opinion.
      RESULTS: Of 620 surveys sent out, 129 (21%) were completed. Of the 129
      respondents, 73% were men, aged 31-79 years, and 92% were board certified, with
      an average of 19 years' experience. The average body mass index of respondents
      was 26 kg/m2 (range 16-40). Only 4% of respondents had a body mass index >30
      kg/m2. Physicians reported a patient obesity rate of 43%. Of the 129 respondents,
      88% believed obesity was difficult to control with diet and exercise alone. Only
      6% thought obesity was best controlled surgically. Also, 85% of respondents had
      referred a patient for gastric bypass, although only 57% were comfortable
      explaining the procedure. The most common reason for refusal to refer was fear of
      complications and death. Additionally, 55% correctly listed a body mass index of
      40 kg/m2 as qualifying for bariatric surgery without comorbidities; 48%
      identified the mortality rate of surgery as <1%, with 4% of respondents reporting
      >10%; and 84% were familiar with gastric bypass, 66% with LapBand, 33% with
      vertical banded gastroplasty, and 5% with duodenal switch. The respondents
      believed that nausea was the most common side effect, followed by anemia and
      fatigue. Finally, 53% believed bowel obstruction was common. CONCLUSIONS: The
      results of our study have shown that misconceptions about bariatric surgery exist
      in the family practice community despite the increasing frequency of these
      procedures. Educational programs need to be designed to assist family
      practitioners in treating and referring obese patients.

PMID- 17442623
TI  - Routine cholecystectomy is not mandatory during morbid obesity surgery.
AB  - BACKGROUND: Controversy exists concerning the utility of routine cholecystectomy
      during bariatric surgery. We report our series of bariatric surgical procedures
      at our institution without concurrent cholecystectomy. METHODS: From October 2003
      to August 2005, 621 morbidly obese patients underwent a weight loss operation.
      Preoperatively, each patient had undergone abdominal ultrasound (AUS) to evaluate
      for abnormal gallbladder findings. Patients with previous cholecystectomy were
      excluded. Symptomatic patients with AUS findings consistent with gallbladder
      disease underwent concomitant cholecystectomy and bariatric surgery. Asymptomatic
      patients, despite AUS findings, did not undergo cholecystectomy with their
      bariatric operation. A comparison between the preoperative AUS-positive and AUS
      negative, asymptomatic patients after bariatric surgery was performed. RESULTS:
      Of the 621 patients who underwent bariatric surgery, 170 (27%) had undergone
      previous cholecystectomy and were excluded. Of the remaining 451 patients, 17
      with positive AUS findings and symptoms underwent cholecystectomy during
      bariatric surgery. The range of follow-up was 4-25 months. Of the 451 patients,
      324 were asymptomatic and had negative AUS findings and 102 were asymptomatic and
      had positive AUS findings for gallbladder abnormalities. Postoperatively, 29
      asymptomatic/AUS-negative patients (9%) developed symptoms and had positive AUS
      findings. Nine asymptomatic patients with AUS positive findings (9%) developed
      symptoms. Finally, 38 patients (8.4%) went on to undergo elective
      cholecystectomy. These 2 groups were not signficantly different statistically.
      CONCLUSIONS: In this study, the development of symptomatic/AUS-positive
      gallbladder abnormalities was low after obesity surgery, suggesting that
      mandatory cholecystectomy is not required at bariatric surgery.

PMID- 17442624
TI  - Primary care and subspecialty management of morbid obesity: referral patterns for
      bariatric surgery.
AB  - BACKGROUND: The global rise in morbid obesity and associated comorbid diseases
      concerns a wide range of specialists. Although bariatric surgery has been proven
      to be an effective, enduring treatment available for morbid obesity, the rates of
      referral for surgery are not consistent with the number of individuals affected.
      METHODS: A survey of 478 experienced physicians from 6 specialty areas was
      conducted to ascertain the attitudes and practices regarding the treatment of
      morbidly obese patients. RESULTS: Approximately 21% (12% family practitioners and
      34% internists) of patients seen by respondents were morbidly obese. Bariatric
      surgery was perceived as, by far, the most effective morbid obesity treatment
      available (judged to be effective for 49% of patients). Medical treatments were
      perceived as effective for <20% of patients (15% drugs and 23% exercise). Despite
      the respondents' perception that most surgery recipients achieve good to
      excellent long-term results, only 15.4% of patients were referred for
      consultation with a surgeon (8.0% for cardiologists and 26.1% for bariatricians).
      Most physicians were not knowledgeable regarding the National Institutes of
      Health morbid obesity management guidelines. Few could identify a local bariatric
      surgeon. The volume of referrals across all 6 specialty groups was low, at an
      average of 6 patients annually (3 patients for cardiologists and 19 patients for
      bariatricians). CONCLUSIONS: The results of our study have demonstrated that
      primary care physicians and subspecialists see a high proportion of morbidly
      obese patients; however, many are unfamiliar with morbid obesity management and
      surgical referral guidelines. Even though the perception of surgical
      effectiveness was quite high, the referrals for surgery were relatively low.

PMID- 17442625
TI  - Expectant management of the asymptomatic gallbladder at Roux-en-Y gastric bypass.
AB  - BACKGROUND: Because of the claim that about one third of patients develop
      gallstones within 6 months of Roux-en-Y gastric bypass (RYGB), many have
      recommended preoperative ultrasonography for all patients and/or prophylactic
      cholecystectomy (CCY), or ursodiol to prevent stone formation. METHODS:
      Prospective data were collected from 1391 consecutive patients followed up for >
      or = 6 months after RYGB (2000-2005) to assess our practice of not routinely
      removing the gallbladder and not administering ursodiol. RESULTS: Of the 1391
      patients, 334 (24%) had undergone CCY before RYGB. Of the remaining 1057
      asymptomatic patients, 516 had undergone preoperative ultrasonography. Stones
      were identified in 99 (19%), sludge in 5 (0.97%), and polyps in 6 (1.1%). Of the
      984 patients with gallbladders left in situ after RYGB, only 80 (8.1%) became
      symptomatic and required delayed CCY. The average excess weight loss at the
      delayed CCY was 65%. The risk of undergoing delayed CCY seemed to be restricted
      to the first 29 months after RYGB, because none of 165 patients followed up for
      30-144 months required CCY. CONCLUSION: Although CCY should be performed whenever
      symptoms mandate, the value of routine preoperative ultrasonography and CCY was
      not apparent from the results of our study. Waiting until symptoms develop might
      simplify the operative procedure because of the significant weight loss that
      should have occurred after RYGB. Using an expectant approach, most patients
      undergoing RYGB will not require CCY.

PMID- 17442626
TI  - Surgical technique for gastric band placement.

PMID- 17442627
TI  - Infantile and pediatric quinone deficiency diseases.
AB  - Coenzyme Q10 (CoQ10) plays a pivotal role in oxidative phosphorylation (OXPHOS)
      as it distributes electrons between the various dehydrogenases and the cytochrome
      segments of the respiratory chain. Primary coenzyme Q10 deficiency is a rare, but
      possibly treatable, autosomal recessive condition with four major clinical
      presentations, an encephalomyopathic form, a generalized infantile variant with
      severe encephalopathy and renal disease, a myopathic form and an ataxic form. The
      diagnosis of ubiquinone deficiency is supported by respiratory chain analysis and
      eventually by the quantification of CoQ10 in patient tissues. We review here the
      infantile and pediatric quinone deficiency diseases as well as the clinical
      improvement after oral CoQ10 therapy. The clinical heterogeneity of ubiquinone
      deficiency is suggestive of a genetic heterogeneity that should be related to the
      large number of enzymes, and corresponding genes, involved in ubiquinone
      biosynthesis.

PMID- 17442628
TI  - Coenzyme Q10 in phenylketonuria and mevalonic aciduria.
AB  - Mevalonic aciduria (MVA) and phenylketonuria (PKU) are inborn errors of
      metabolism caused by deficiencies in the enzymes mevalonate kinase and
      phenylalanine 4-hydroxylase, respectively. Despite numerous studies the factors
      responsible for the pathogenicity of these disorders remain to be fully
      characterised. In common with MVA, a deficit in coenzyme Q10 (CoQ10)
      concentration has been implicated in the pathophysiology of PKU. In MVA the
      decrease in CoQ10 concentration may be attributed to a deficiency in mevalonate
      kinase, an enzyme common to both CoQ10 and cholesterol synthesis. However,
      although dietary sources of cholesterol cannot be excluded, the low/normal
      cholesterol levels in MVA patients suggests that some other factor may also be
      contributing to the decrease in CoQ10.The main factor associated with the low
      CoQ10 level of PKU patients is purported to be the elevated phenylalanine level.
      Phenylalanine has been shown to inhibit the activities of both 3-hydroxy-3
      methylglutaryl-CoA reductase and mevalonate-5-pyrophosphate decarboxylase,
      enzymes common to both cholesterol and CoQ10 biosynthesis. Although evidence of a
      lowered plasma/serum CoQ10 level has been reported in MVA and PKU, few studies
      have assessed the intracellular CoQ10 concentration of patients. Plasma/serum
      CoQ10 is influenced by dietary intake as well as its lipoprotein content and
      therefore may be limited as a means of assessing intracellular CoQ10
      concentration. Whether the pathogenesis of MVA and PKU are related to a loss of
      CoQ10 has yet to be established and further studies are required to assess the
      intracellular CoQ10 concentration of patients before this relationship can be
      confirmed or refuted.

PMID- 17442629
TI  - Identification of a strand-related bias in the PCNA-mediated bypass of
      spontaneous lesions by yeast Poleta.
AB  - Translesion synthesis (TLS) DNA polymerases are specialized to bypass lesions
      that block replicative polymerases and prevent complete genome duplication.
      Current TLS models hypothesize that PCNA, the polymerase processivity clamp, is
      important for regulating the access and loading of the low fidelity TLS
      polymerases onto DNA in response to replication-blocking lesions. PCNA binds to
      the C-terminus of yeast Poleta, for example, and this interaction is required for
      cell survival after UV irradiation. Previously, we identified two spontaneous,
      Polzeta-dependent "complex" mutation hotspots using the lys2DeltaA746 frameshift
      reversion assay in repair-compromised cells. In the current study we observed an
      accumulation of Polzeta-dependent complex frameshifts at a third hotspot in
      Poleta-deficient cells. Interestingly, the sequence of this third hotspot is the
      reverse complement of the two hotspots previously identified, suggesting that the
      utilization of Polzeta and Poleta may be related to the position of the relevant
      lesion on either the leading- or lagging-strand template. Using the lys2DeltaA746
      assay system, we investigated changes in the accumulation of complex events at
      hotspots when the direction of replication was reversed in repair-compromised
      cells with either wildtype Poleta, a deletion of Poleta, or a mutant of Poleta
      that cannot interact with PCNA. Our results suggest that there is a polymerase
      hierarchy between Poleta and Polzeta in the bypass of certain lesions and that
      the interaction of Poleta with PCNA is needed for some, but not all, spontaneous
      lesion bypass.

PMID- 17442631
TI  - Cardiac adaptation to chronic high-altitude hypoxia: beneficial and adverse
      effects.
AB  - This review deals with the capability of the heart to adapt to chronic hypoxia in
      animals exposed to either natural or simulated high altitude. From the broad
      spectrum of related issues, we focused on the development and reversibility of
      both beneficial and adverse adaptive myocardial changes. Particular attention was
      paid to cardioprotective effects of adaptation to chronic high-altitude hypoxia
      and their molecular mechanisms. Moreover, interspecies and age differences in the
      cardiac sensitivity to hypoxia-induced effects in various experimental models
      were emphasized.

PMID- 17442632
TI  - Chronic intermittent hypoxia modulates nNOS mRNA and protein expression in the
      rat hypothalamus.
AB  - Exposure to chronic intermittent hypoxia (CIH) as observed in obstructive sleep
      apnea (OSA) elicits a sustained elevation of sympathetic activity and arterial
      blood pressure. Our overall hypothesis is that intermittent hypoxia might
      increase sympathetic activity, in part by altering neuronal nitric oxide synthase
      (nNOS) expression in the hypothalamus, where nitric oxide is sympathoinhibitory.
      In this study, we begin investigation of this hypothesis by testing the more
      specific hypothesis that the CIH alters nNOS expression in regions of the
      hypothalamus associated with cardiovascular regulation. To test the effect of CIH
      on NOS expression we subjected male Sprague-Dawley rats to cyclic intermittent
      hypoxia for 8h/day, for 35 days. Experimental rats showed an increase in systemic
      blood pressure. In situ hybridization and immunohistochemistry were performed on
      hypothalamic sections, respectively. The CIH rats displayed significantly lower
      levels of both nNOS mRNA and protein in the paraventricular hypothalamic nucleus
      (PVN) with different changes in the subareas of the PVN. There was a decreased
      level of nNOS mRNA and protein in the subfornical organ and the periventricular
      hypothalamic nucleus of the CIH rats, but no significant change in the supraoptic
      nucleus or the lateral hypothalamic area. This work suggests that examination of
      central regulation of sympathetic activity may help elucidate the mechanisms of
      hypertension after CIH.

PMID- 17442633
TI  - Oxygen sensitive Kv channels in the carotid body.
AB  - Hypoxic inhibition of K(+) channels has been documented in many native
      chemoreceptor cells, and is crucial to initiate reflexes directed to improve
      tissue O(2) supply. In the carotid body (CB) chemoreceptors, there is a general
      consensus regarding the facts that a decrease in P(O2) leads to membrane
      depolarization, increase of Ca(2+) entry trough voltage-dependent Ca(2+) channels
      and Ca(2+)-dependent release of neurotransmitters. Central to this pathway is the
      modulation by hypoxia of K(+) channels that triggers depolarization. However, the
      details of this process are still controversial, and even the molecular nature of
      these oxygen-sensitive K(+) (K(O2)) channels in the CB is hotly debated. Clearly
      there are inter-species differences, and even in the same preparation more that
      one K(O2) may be present. Here we recapitulate our present knowledge of the role
      of voltage dependent K(+) channels as K(O2) in the CB from different species, and
      their functional contribution to cell excitability in response to acute and
      chronic exposure to hypoxia.

PMID- 17442634
TI  - Comparison of different ligand densities in immunoaffinity chromatography of the
      plantibody HB-01 coupled to Sepharose CL-4B to purify the rHBsAg.
AB  - This paper evaluates the immunopurification behavior of a plantibody HBsAg
      specific plantibody coupled to Sepharose CL-4B at different ligand densities.
      Results show no significant differences in the adsorption and elution capacities,
      and rHBsAg recovery of immunosorbents at 3.43, 4.45, and 5.31 mg/mL of ligand
      densities compared to its mouse-derived mAb counterpart consistently used in the
      rHBsAg purification process. Therefore, plantibody ligand densities higher than
      3.43 mg/mL do not improve the immunopurification behavior of this immunosorbent,
      but increase the antibody consumption and the Hepatitis B vaccine cost.
      Immunosorbent of 2.23 mg/mL of ligand density demonstrated a poor performance.
      The IgG leached detectable level never exceeded the approved limit (3 ng
      IgG/microg rHBsAg). Values close to this limit were only observed at the ligand
      density of 5.31 and 2.27 mg/mL. In the case of the ligand density of 2.23 mg/mL
      the IgG leached value was high (2.90 ng IgG/microg rHBsAg) due to a low level of
      eluted antigen. In conclusion, it supports feasibility of using this plantibody
      at 3.43 mg/mL of ligand density for large-scale immunopurification of rHBsAg for
      human use, avoiding the biosafety and ethical concerns of the massive use of
      animals for this purpose.

PMID- 17442635
TI  - Gas chromatographic-mass spectrometric method for the determination of the
      herbicides paraquat and diquat in plasma and urine samples.
AB  - In the present work, a method was developed and optimized aiming to determinate
      the herbicides paraquat (PQ) and diquat (DQ) in human plasma and urine samples.
      An initial procedure of chemical reduction of the analytes by adding NaBH4
      directly in the buffered samples (pH 8.0) was performed. This procedure was
      necessary to convert the quaternary ammonium substances into more volatile
      compounds for gas chromatographic analysis. The reduction compounds were
      extracted with C18 cartridges (solid-phase extraction). Ethyl paraquat (EPQ) was
      used as internal standard (IS). Gas chromatography-mass spectrometry (GC-MS) was
      used to identify and quantify the analytes in selected ion monitoring (SIM) mode.
      The limits of detection were 0.05 mg/l for both PQ and DQ. By using the weighted
      least squares linear regression (1/x1/2 for plasma and 1/y for urine), the
      accuracy of the analytical method was improved at the lower end of the
      calibration curve (from 0.1 to 50 mg/l; r>0.98). This method can be readily
      utilized as an important tool to confirm the suspicion of PQ and/or DQ poisoning
      and evaluate the extent of the intoxication.

PMID- 17442636
TI  - Liquid chromatographic method with amperometric detection to determine acteoside
      in rat blood and brain microdialysates and its application to pharmacokinetic
      study.
AB  - A simple and sensitive liquid chromatography with amperometric detection was
      developed for the first time to monitor the protein-unbound acteoside in the rat
      blood and brain microdialysate by microdialysis technique. Microdialysis samples
      without further cleanup procedures were directly injected into the HPLC and
      separated using a reversed-phase C18 column (150 mmx2 mm, i.d. 5 microm)
      maintained at ambient temperature and a mobile phase comprised of acetonitrile-50
      mM monosodium phosphate (pH 2.8) (17:83, v/v) with a flow rate of 0.2 mL/min.
      Based on the experimental voltamogram, the applied potential was set at +0.9 V
      oxidative mode. The concentration-response relationship was linear (r2>0.99) over
      a concentration range of 5-500 ng/mL; method precision and accuracy fell within
      predefined limits (less than 20%). The developed method was applied to assess the
      pharmacokinetics of acteoside, and the results suggested that acteoside was
      fitted better by the two-compartmental model following a single intravenous
      injection of acteoside. Acteoside was unable to be detected in the brain
      dialysate. The distribution and elimination half-lives of unbound acteoside in
      the blood were 5 and 28 min, respectively, which suggested the rapid distribution
      of acteoside.

PMID- 17442637
TI  - Preparative isolation and purification of triterpene saponins from Clematis
      mandshurica by high-speed counter-current chromatography coupled with evaporative
      light scattering detection.
AB  - Preparative high-speed counter-current chromatography (HSCCC) coupled with
      evaporative light scattering detection (ELSD) was successfully applied to the
      isolation and purification of four triterpene saponins from Clematis mandshurica
      by one-step separation. The solvent system was composed of ethyl acetate-n
      butanol-ethanol-0.05% TFA (5:10:2:20, v/v). The purities of all the saponins
      obtained were better than 97%. The structures of the compounds were elucidated by
      the means of spectroscopic methods.

PMID- 17442638
TI  - Comparison of strategies for the isolation of PCR-compatible, genomic DNA from a
      municipal biogas plants.
AB  - The goal of the project was the extraction of PCR-compatible genomic DNA
      representative of the entire microbial community from municipal biogas plant
      samples (mash, bioreactor content, process water, liquid fertilizer). For the
      initial isolation of representative DNA from the respective lysates, methods were
      used that employed adsorption, extraction, or precipitation to specifically
      enrich the DNA. Since no dedicated method for biogas plant samples was available,
      preference was given to kits/methods suited to samples that resembled either the
      bioreactor feed, e.g. foodstuffs, or those intended for environmental samples
      including wastewater. None of the methods succeeded in preparing DNA that was
      directly PCR-compatible. Instead the DNA was found to still contain considerable
      amounts of difficult-to-remove enzyme inhibitors (presumably humic acids) that
      hindered the PCR reaction. Based on the isolation method that gave the highest
      yield/purity for all sample types, subsequent purification was attempted by
      agarose gel electrophoresis followed by electroelution, spermine precipitation,
      or dialysis through nitrocellulose membrane. A combination of phenol/chloroform
      extraction followed by purification via dialysis constituted the most efficient
      sample treatment. When such DNA preparations were diluted 1:100 they did no
      longer inhibit PCR reactions, while they still contained sufficient genomic DNA
      to allow specific amplification of specific target sequences.

PMID- 17442639
TI  - Determination of dimenhydrinate in human plasma by liquid chromatography
      electrospray tandem mass spectrometry: application to a relative bioavailability
      study.
AB  - Here we present a sensitive and specific liquid chromatography-tandem mass
      spectrometric method for the quantification of dimenhydrinate (I) in human
      plasma. Sample preparation is conducted using citalopram (II) addition as an
      internal standard (IS), liquid-liquid extraction with basified plasma using a
      mixture hexane/acetate (1:1, v/v) as the extracting solvent, and the final
      extract reconstituted in the mobile phase. I and II (IS) were injected in a C8
      column with the mobile phase composed of methanol:isopropanol:water:formic acid
      (78.00:19.92:2.00:0.08, v/v/v/v) and monitored using a positive electrospray
      source with tandem mass spectrometry analyses. The selected reaction monitoring
      (SRM) was set using precursor ion and product ion combinations of m/z 256.0>167.0
      and m/z 325.0>109.0 for I and II, respectively. The limit of quantification (LOQ)
      was 0.4 ng/mL, the dynamic range being 0.4-200 ng/mL. Validation results on
      linearity, specificity, accuracy, precision and stability, as well as on
      application to the analysis of plasma samples taken up to 24 h after oral
      administration of 100 mg of dimenhydrinate in healthy volunteers demonstrated its
      applicability to bioavailability studies.

PMID- 17442640
TI  - Separation and quantification of two diastereomers of a Drug Candidate in rat
      plasma by ultra-high pressure liquid chromatography/mass spectrometry.
AB  - Ultra-high pressure liquid chromatography (UHPLC) is a relatively new technology
      which utilizes chromatographic media with a 1.7 microm particle size. This
      technology has the potential to offer significant advantages in resolution,
      speed, and sensitivity for analytical determinations, particularly when coupled
      with mass spectrometric detection. Drug Candidate A, under development at Merck
      Research Laboratories, contains two chiral centers which have the absolute
      configuration R, S. Under in vivo and ex vivo conditions, one of the chiral
      centers readily epimerizes to produce the R, R diastereomer. Initially, a
      traditional high performance liquid chromatography/tandem mass spectrometry (HPLC
      MS/MS) method was developed to separate and quantify these two diastereomers in
      rat plasma. The lower limit of quantification (LOQ) of the two analytes was 2
      ng/mL, and a chromatographic run time of approximately 11 min was needed to
      separate R, S-(A) and R, R-(A). In this study, we explored a simple and robust
      UHPLC-MS/MS method in order to increase sample throughput and productivity. We
      were able to achieve a two-fold reduction in the lower limit of quantification
      and a three-fold reduction in retention time utilizing the UHPLC method, while
      keeping the same sample extraction procedure and similar MS/MS methodology. The
      new method exhibited good intra- and inter-day accuracy and precision, and was
      linear over a dynamic range of 1-500 ng/mL for each diastereomer. The method was
      successfully applied for the determination of R, S-(A) and R, R-(A)
      concentrations for in vitro and in vivo studies of epimerization of A in Sprague
      Dawley rats.

PMID- 17442641
TI  - Analysis of 8-hydroxy-2'-deoxyguanosine in urine using high-performance liquid
      chromatography-electrospray tandem mass spectrometry.
AB  - 8-hydroxy-2'-deoxyguanosine (8-OHdG) is a widely used biomarker of oxidative
      stress in research related to DNA, protein damage as well as lipid peroxidation.
      HPLC-MS/MS with electrospray ionization (ESI) and the use of isotopically
      labelled 8-OHdG as an internal standard allows a simple quantification of 8-OHdG
      in urine samples. HPLC separation utilized the peak cutting technique and a 1.5
      mmx120 mm analytical anion exchange column. Novel method entails only minimal
      sample handling including the addition of a buffer and an internal standard
      followed by centrifugation before the samples are ready for analysis. The levels
      of 8-OHdG in human urine samples (n=246) varied from 0.16 to 16.48 microg/L and
      the corresponding creatinine-normalized values were ranged from 0.49 to 14.27
      microg of 8-OHdG/g creatinine. The correlation between the developed HPLC-MS/MS
      method and the existing HPLC-EC method was good with an R2 value of 0.8707.

PMID- 17442642
TI  - Simultaneous quantification of malonyl-CoA and several other short-chain acyl
      CoAs in animal tissues by ion-pairing reversed-phase HPLC/MS.
AB  - Malonyl-CoA is a key intermediate involved in lipid synthesis and lipid
      oxidation. Here, we report on a novel method for the quantification of malonyl
      CoA and seven other short-chain acyl-CoAs in various rat and mouse tissues using
      ion-pairing reversed-phase HPLC/MS. This method is capable of measuring malonyl
      CoA, free coenzyme A (CoASH), acetyl-CoA, beta-hydroxyl-butyryl-CoA (HB-CoA), 3
      hydroxy-3-methyl-glutaryl-CoA (HMG-CoA), propionyl-CoA, succinyl-CoA, and
      isobutyryl-CoA simultaneously with a dynamic linear range over two orders of
      magnitude in a 7.0 min HPLC gradient run. The lower limit of quantification
      (LLOQ) was 0.225 pmol for all acyl-CoAs studied, except for HMG-CoA which had a
      higher LLOQ of 0.90 pmol. The interference of HB-CoA on the quantification of
      malonyl-CoA in animal tissues was also explored for the first time.

PMID- 17442643
TI  - Concurrent determination of ezetimibe and its phase-I and II metabolites by HPLC
      with UV detection: quantitative application to various in vitro metabolic
      stability studies and for qualitative estimation in bile.
AB  - Simultaneous separation and quantification of ezetimibe (EZM) and its phase-I
      metabolite i.e., ezetimibe ketone (EZM-K) and phase-II metabolite i.e., ezetimibe
      glucuronide (EZM-G) in various matrices was accomplished by gradient HPLC with UV
      detection. The assay procedure involved deproteinization of 500 microL of either
      incubation or bile sample containing analytes and internal standard (IS,
      theophylline) with 75 microL acetonitrile containing 25% perchloric acid. An
      aliquot of 100 microL supernatant was injected onto a C18 column. The
      chromatographic separation was achieved by gradient elution consisting of 0.05 M
      formic acid:acetonitrile:methanol:water at a flow rate of 1.0 mL/min. The
      detection of analyte peaks were achieved by monitoring the eluate using an UV
      detector set at 250 nm. Nominal retention times of IS, EZM-G, ezetimibe ketone
      glucuronide (EZM-KG), EZM and EZM-K were 9.39, 24.23, 27.82, 29.04 and 30.56 min,
      respectively. Average extraction efficiencies of EZM, EZM-G and IS was >75-80%
      and for EZM-K was >50% from all the matrices tested. Limit of quantitation (LOQ)
      for EZM, EZM-K and EZM-G was 0.02 microg/mL. Due to the lack of availability of
      reference standard of EZM-KG, the recovery and LOQ aspects for this metabolite
      were not assessed. Overall, the method is suitable for simultaneous measurement
      of EZM, and its phase-I and phase-II metabolite (EZM-G) in in vitro and in vivo
      studies.

PMID- 17442644
TI  - Interactions of rotor subunits in the chloroplast ATP synthase modulated by
      nucleotides and by Mg2+.
AB  - ATP synthases - rotary nano machines - consist of two major parts, F(O) and F(1),
      connected by two stalks: the central and the peripheral stalk. In spinach
      chloroplasts, the central stalk (subunits gamma, epsilon) forms with the cylinder
      of subunits III the rotor and transmits proton motive force from F(O) to F(1),
      inducing conformational changes of the catalytic centers in F(1). The epsilon
      subunit is an important regulator affecting adjacent subunits as well as the
      activity of the whole protein complex. Using a combination of chemical cross
      linking and mass spectrometry, we monitored interactions of subunit epsilon in
      spinach chloroplast ATP synthase with III and gamma. Onto identification of
      interacting residues in subunits epsilon and III, one cross-link defined the
      distance between epsilon-Cys6 and III-Lys48 to be 9.4 A at minimum. epsilon-Cys6
      was competitively cross-linked with subunit gamma. Altered cross-linking yields
      revealed the impact of nucleotides and Mg(2+) on cross-linking of subunit
      epsilon. The presence of nucleotides apparently induced a displacement of the N
      terminus of subunit epsilon, which separated epsilon-Cys6 from both, III-Lys48
      and subunit gamma, and thus decreasing the yield of the cross-linked subunits
      epsilon and gamma as well as epsilon and III. However, increasing concentrations
      of the cofactor Mg(2+) favoured cross-linking of epsilon-Cys6 with subunit gamma
      instead of III-Lys48 indicating an approximation of subunits gamma and epsilon
      and a separation from III-Lys48.

PMID- 17442645
TI  - An EcoRI-RsrI chimeric restriction endonuclease retains parental sequence
      specificity.
AB  - To test their structural and functional similarity, hybrids were constructed
      between EcoRI and RsrI, two restriction endonucleases recognizing the same DNA
      sequence and sharing 50% amino acid sequence identity. One of the chimeric
      proteins (EERE), in which the EcoRI segment His147-Ala206 was replaced with the
      corresponding RsrI segment, showed EcoRI/RsrI-specific endonuclease activity.
      EERE purified from inclusion bodies was found to have approximately 100-fold
      weaker activity but higher specific DNA binding affinity, than EcoRI. Increased
      binding is consistent with results of molecular dynamics simulations, which
      indicate that the number of hydrogen bonds formed with the recognition sequence
      increased in the chimera as compared to EcoRI. The success of obtaining an EcoRI
      RsrI hybrid endonuclease, which differs from EcoRI by 22 RsrI-specific amino acid
      substitutions and still preserves canonical cleavage specificity, is a sign of
      structural and functional similarity shared by the parental enzymes. This
      conclusion is also supported by computational studies, which indicate that
      construction of the EERE chimera did not induce substantial changes in the
      structure of EcoRI. Surprisingly, the chimeric endonuclease was more toxic to
      cells not protected by EcoRI methyltransferase, than the parental EcoRI mutant.
      Molecular modelling revealed structural alterations, which are likely to impede
      coupling between substrate recognition and cleavage and suggest a possible
      explanation for the toxic phenotype.

PMID- 17442646
TI  - The conformation of acetylated virginiamycin M1 and virginiamycin M1 in explicit
      solvents.
AB  - The three-dimensional structure of acetylated virginiamycin M(1) (acetylated VM1)
      in chloroform and in a water/acetonitrile mixture (83:17 v/v) have been
      established through 2D high resolution NMR experiments and molecular dynamics
      modeling and the results compared with the conformation of the antibiotic VM1 in
      the same and other solvents. The results indicated that acetylation of the C-14
      OH group of VM1 caused it to rotate about 90 degrees from the position it assumed
      in non-acetylated VM1. The conformation of both VM1 and acetylated VM1 appear to
      flatten in moving from a nonpolar to polar solvent. However, the acetylated form
      has a more hydrophobic nature. The acetylated VM1 in chloroform and in
      water/acetonitrile solution had a similar configuration to that of VM1 bound to
      50S ribosomes and to the Vat(D) active sites as previously determined by X-ray
      crystallography. Docking studies of VM1 to the 50S ribosomal binding site and the
      Vat(D) gave conformations very similar to those derived from X-ray
      crystallographic studies. The docking studies with acetylated VM1 suggested the
      possibility of a hydrogen bond from the acetyl carbonyl group oxygen of
      acetylated VM1 to the 2' hydroxyl group of ribose of adenosine 2538 at the
      ribosomal VM1 binding site. No hydrogen bonds between acetylated VM1 and the
      Vat(D) active sites were found; the loss of this binding interaction partly
      accounts for the release of the product from the active site.

PMID- 17442647
TI  - Present technique and long-term results of toe-to-antebrachial stump
      transplantation.
AB  - Complete hand amputation has been considered conventionally as an indication for
      the use of mechanical prosthetic devices in order to regain some hand like
      function. A microsurgical option to create a new pinching ability after wrist
      amputation has been used in a series of 13 patients. The actual operation
      technique is presented in detail. It was designed by the senior author in 1981
      and applied into clinical use in 1983. In order to evaluate the functional
      results and patient satisfaction in long-term, a questionnaire was sent to 12
      patients and 11 patients were interviewed, examined clinically and studied with a
      hand function scoring test according Sollerman. The operated series consist of 12
      adults with posttraumatic distal antebrachial or wrist amputations and 1
      adolescent boy with a congenital wrist level amputation. There were 3 females and
      10 males in the series. The satisfaction to achieved result was generally good.
      The ADL section of Tamai score and the one we used correlated well with each
      other and patient satisfaction. Sollerman hand function test gave worse results
      in two blind patients and same occurred in two short antebrachial stump patients.
      However the satisfaction was much better in Tamai score among blind patients,
      with wrist amputation level amputations. In our opinion this single toe transfer
      method gives an acceptable pinch reconstruction for hand amputation patients. We
      measured pinch strength and total active motion. They averaged about half of the
      normal values. The reconstruction is suitable to the patients, who are not
      willing to donate multiple toes or who are aware and concerned about the risks of
      human hand transplantation, which necessarily will need a life-long
      immunosuppressive medication to prevent from rejection.

PMID- 17442648
TI  - Comment on 'Morphea of the breast. Two case reports and discussion of the
      literature'.

PMID- 17442649
TI  - Load distribution and the predictive power of morphological indices in the distal
      radius and tibia by high resolution peripheral quantitative computed tomography.
AB  - A 3D high resolution peripheral quantitative computed tomography scanner (HR
      pQCT) (XtremeCT, Scanco Medical, voxel size 82 microm) has been recently
      developed that can perform in vivo human measurements on peripheral sites,
      including the wrist and tibia. The goals of this study were to use HR-pQCT
      measurements to determine the ability of morphological and density measurements
      to predict bone apparent stiffness and apparent Young's modulus in the distal
      radius and tibia, to determine the relative importance of cortical and trabecular
      bone in carrying load in the human distal radius and tibia. Furthermore, the
      ability of a sub-volume of trabecular bone apparent Young's modulus to predict
      the Young's modulus of a whole radius and tibia section was determined. A total
      of 25 measurements of the radius and 12 measurements of the tibia were used for
      morphological and finite element analyses of sections, and sub-volume cubes of
      trabecular bone from the distal radius and tibia. The subjects were chosen to
      obtain a large variation in age ranges and bone architecture and density. By
      combining multiple measurements, a strong ability to predict bone apparent
      stiffness and apparent Young's modulus was found for morphological and density
      measurements in the radius and tibia (R(2)>0.80). The relative importance of the
      trabecular and cortical bone in carrying load was also found to vary consistently
      with location in the sample for both the radius and the tibia. This indicates
      that measurements of the cortical and trabecular bone are required for assessing
      fracture risk. A cubic section of trabecular bone was found to be insufficient to
      accurately represent the apparent bone Young's modulus of a radius or tibia
      section. Morphological and density measurements of the distal radius and tibia
      have been shown in this study to predict bone apparent Young's modulus and
      apparent stiffness, and may indicate when a more time consuming finite element
      analysis is warranted. It should be noted that these results may be an
      overestimation of the predictive ability of structural parameters, as the
      influence of bone density is removed from the finite element analyses, and the
      results were only influenced by bone structure. A measurement of bone apparent
      Young's modulus is independent of subject size (as opposed to reaction force),
      and may provide the ability to distinguish between two patients that have similar
      mean morphological and density measurements; but different overall structures,
      and therefore, different fracture risk.

PMID- 17442650
TI  - Vaccinating in disease-free regions: a vaccine model with application to yellow
      fever.
AB  - Concerns regarding natural or induced emergence of infectious diseases have
      raised a debate on the pros and cons of pre-emptive vaccination of populations
      under uncertain risk. In the absence of immediate risk, ethical issues arise
      because even smaller risks associated with the vaccine are greater than the
      immediate disease risk (which is zero). The model proposed here seeks to
      formalize the vaccination decision process looking from the perspective of the
      susceptible individual, and results are shown in the context of the emergence of
      urban yellow fever in Brazil. The model decomposes the individual's choice about
      vaccinating or not into uncertain components. The choice is modelled as a
      function of (i) the risk of a vaccine adverse event, (ii) the risk of an outbreak
      and (iii) the probability of receiving the vaccine or escaping serious disease
      given an outbreak. Additionally, we explore how this decision varies as a
      function of mass vaccination strategies of varying efficiency. If disease is
      considered possible but unlikely (risk of outbreak less than 0.1), delay
      vaccination is a good strategy if a reasonably efficient campaign is expected.
      The advantage of waiting increases as the rate of transmission is reduced (low
      R0) suggesting that vector control programmes and emergency vaccination
      preparedness work together to favour this strategy. The opposing strategy,
      vaccinating pre-emptively, is favoured if the probability of yellow fever
      urbanization is high or if expected R0 is high and emergency action is expected
      to be slow. In summary, our model highlights the nonlinear dependence of an
      individual's best strategy on the preparedness of a response to a yellow fever
      outbreak or other emergent infectious disease.

PMID- 17442651
TI  - International classification of functioning, disability and health.

PMID- 17442652
TI  - Horseback riding as therapy for children with cerebral palsy: is there evidence
      of its effectiveness?
AB  - A systematic review of the literature on horseback riding therapy as an
      intervention for children with cerebral palsy (CP) was carried out. The terms
      horse, riding, hippotherapy, horseback riding therapy, equine movement therapy,
      and cerebral palsy were searched in electronic databases and hand searched.
      Retrieved articles were rated for methodological quality using PEDro scoring to
      assess the internal validity of randomized trials and the Newcastle Ottawa
      Quality Assessment Scale to assess cohort studies. PICO questioning (Population,
      Intervention, Comparison, and Outcomes) was used to identify questions of
      interest to clinicians for outcomes within the context of the International
      Classification of Functioning, Disability and Health. Levels of evidence were
      then accorded each PICO question. There is Level 2a evidence that hippotherapy is
      effective for treating muscle symmetry in the trunk and hip and that therapeutic
      horseback riding is effective for improved gross motor function when compared
      with regular therapy or time on a waiting list. No studies addressed
      participation outcomes.

PMID- 17442653
TI  - Measurement practices in pediatric rehabilitation: a survey of physical
      therapists, occupational therapists, and speech-language pathologists in Ontario.
AB  - We investigated measurement practices in pediatric rehabilitation. We conducted a
      survey of 63 physical, 72 occupational, and 74 speech-language therapists working
      in one of 16 children's rehabilitation programs in Ontario, Canada. Therapists
      were surveyed about their measurement practices, and their confidence, beliefs,
      and attitudes about measurement. Results showed that standardized clinical
      measures were used frequently, but were often modified. Clinicians rated
      themselves as least comfortable with statistical concepts related to the
      uncertainty in test scores, and rated factors related to finding appropriate
      measures as the most important influences on their measurement practices. Some
      variance in measurement attitudes and practices was associated with treatment
      centre of practice, suggesting that there may be organizational or peer
      influences on measurement behaviour. The results have implications for continuing
      education, measurement development, and interventions designed to facilitate
      sound measurement practices.

PMID- 17442654
TI  - Handwriting performance on the ETCH-M of students in a grade one regular
      education program.
AB  - This nonexperimental correlational study describes handwriting performance in 69
      typically developing first graders (mean age = 82.0 months +/-3.6) using the
      Evaluation Tool of Children's Handwriting- Manuscript. The relationship between
      handwriting and specific sensorimotor components was also examined and revealed
      modest associations (r = 0.32-0.40; p < 0.05). Mean legibility scores ranged from
      68% to 87% with wide variability in speed. Boys demonstrated significantly lower
      mean legibility scores compared with girls. Teacher rating of handwriting and the
      ETCH-M scores were modestly correlated (r =-0.37 to -43; p < 0.01). Handwriting
      predictors included in-hand manipulation, visual motor control, upper limb speed,
      dexterity, and steadiness. The factors contributing to legible handwriting are
      multifactorial and complex. The results have implications for identification of
      students in first grade whose handwriting is below age expectations.

PMID- 17442655
TI  - Use of the FirstSTEp screening tool with children exposed to domestic violence
      and homelessness: a group case study.
AB  - Children who experience homelessness and domestic violence enter early childhood
      programs with developmental and behavioral challenges. Thoroughly evaluating
      these children can be daunting for daycare staff without advanced training.
      Occupational therapists can provide child development expertise and consultation.
      This group case study examined the FirstSTEp screening tool's ability to measure
      the behavioral, developmental, and emotional changes of 19 pre-schoolers who
      experienced homelessness and witnessed domestic violence. The tool was found to
      be effective with this population.

PMID- 17442656
TI  - Factors influencing mothers' learning from paediatric therapists: a qualitative
      study.
AB  - A paradigm shift in community-based paediatric therapy has changed the role of
      parents from passive observers to active partners. As a result, therapists need
      to acquire an expanded set of skills, which include partnership building and
      teaching to ensure effective service delivery. This qualitative study explored
      factors influencing mothers' learning about their child's special needs from
      their child's therapist. Nine mothers were interviewed regarding their
      experiences working with, and learning from, their therapists. The interviews
      were audiotaped, transcribed verbatim, and thematically analyzed. Two major
      themes emerged: Relationship: More Than Just a Client; and Learning: The Best
      Teaching Needs a Relationship. Mothers were content with their therapists'
      approach to teaching, even when it differed from their own typical learning
      style. Therapists need to be cognizant of their relationship with mothers and
      ensure that the mothers' needs are being met.

PMID- 17442658
TI  - The use of pharmacokinetic and pharmacodynamic end points to determine the dose
      of AQ4N, a novel hypoxic cell cytotoxin, given with fractionated radiotherapy in
      a phase I study.
AB  - BACKGROUND: AQ4N (1,4-bis[[2-(dimethylamino)ethyl] amino]-5,8-dihydroxyanthracene
      9, 10-dione bis-N-oxide dihydrochloride) is a prodrug which is selectively
      activated within hypoxic tissues to AQ4, a topoisomerase II inhibitor and DNA
      intercalator. PATIENTS AND METHODS: In the phase I study, 22 patients with
      oesophageal carcinoma received an i.v. infusion of AQ4N (22.5-447 mg/m(2))
      followed, 2 weeks later, by further infusion and radiotherapy. Pharmacokinetics
      and lymphocyte AQ4N and AQ4 levels were measured after the first dose. At 447
      mg/m(2), biopsies of tumour and normal tissue were taken after AQ4N
      administration. RESULTS: Drug-related adverse events were blue discolouration of
      skin and urine, grade 2-3 lymphopenia, grade 1-3 fatigue, grade 1-2 anaemia,
      leucopenia and nausea. There were no drug-related serious adverse events (SAEs).
      Three patients had reductions in tumour volume >50%, nine had stable disease.
      Pharmacokinetics indicated predictable clearance. Plasma area under the curve
      (AUC) at 447 mg/m(2) exceeded AQ4N concentrations in mice at therapeutic doses
      and tumour biopsies contained concentrations of AQ4 greater than those in normal
      tissue. Tumour concentrations of AQ4 exceeded in vitro IC(50) values for most
      cell lines investigated. CONCLUSIONS: No dose-limiting toxic effects were
      observed and a maximum tolerated dose was not established. Tumour AQ4
      concentrations and plasma AUC at 447 mg/m(2) exceeded active levels in
      preclinical models. This dose was chosen for future studies with radiotherapy.

PMID- 17442660
TI  - Intriguing issues of EGFR targeting in head and neck cancer.

PMID- 17442659
TI  - Oral ibandronate is as active as intravenous zoledronic acid for reducing bone
      turnover markers in women with breast cancer and bone metastases.
AB  - BACKGROUND: Phase III study comparing the effect of oral ibandronate and
      intravenous zoledronic acid on bone markers. PATIENTS AND METHODS: Breast cancer
      patients with bone metastases received ibandronate 50 mg/day (n = 137) or
      zoledronic acid 4 mg every 4 weeks (n = 138) for 12 weeks. The primary end point
      was mean percentage change in serum levels of cross-linked C-terminal telopeptide
      of type I collagen (S-CTX) at week 12. Urinary CTX (U-CTX), bone alkaline
      phosphatase (ALP), amino-terminal procollagen propeptide of type I collagen
      (PINP) and osteocalcin (OC) were also measured and bone pain and safety assessed.
      RESULTS: Both bisphosphonates significantly reduced S-CTX (mean ibandronate 76%
      +/- 29 (SD) versus mean zoledronic acid 73% +/- 47; P < 0.001 for both versus
      baseline) and U-CTX (ibandronate 78% +/- 50 versus zoledronic acid 86% +/- 17; P
      < 0.001). The difference in S-CTX between treatments was 0.6% (confidence
      interval -1.7% to 3.0%), which was within the prespecified noninferiority margin.
      Bone ALP, PINP and OC decreased by 26%-47% compared with baseline with both
      bisphosphonates. Compared with zoledronic acid, ibandronate patients reported
      fewer adverse events overall (65.0% versus 75.9%), and on days 1-3 (8.0% versus
      47.5%), including less pyrexia (overall incidence 0% versus 16.8%) and bone pain
      (5.8% versus 12.4%). CONCLUSIONS: Oral ibandronate was well tolerated and
      statistically noninferior to zoledronic acid for percentage change in the bone
      resorption marker, S-CTX.

PMID- 17442661
TI  - Diffuse punctate keratitis in a patient treated with cetuximab as monotherapy.

PMID- 17442662
TI  - Positive impact of selective outpatient management of high-risk acute myelogenous
      leukemia on the incidence of septicemia.
AB  - BACKGROUND: Curative intent chemotherapy for acute myelogenous leukemia (AML)
      leads to prolonged severe neutropenia, during which patients are highly
      susceptible to infection. Traditionally these high-risk patients were treated as
      inpatients. Our center recently implemented a selective ambulatory management
      policy for AML patients undergoing chemotherapy. MATERIALS AND METHODS: A
      retrospective analysis was conducted to assess the occurrence of septicemia in
      AML patients treated over a 5 years period with curative intent chemotherapy.
      This review encompasses a change in policy from primarily inpatient care to
      selective outpatient management coupled with prophylactic antibiotic therapy.
      RESULTS: A total of 294 patients, receiving 623 cycles of chemotherapy were
      identified. A significant decrease in septicemia was observed from the inpatient
      to outpatient cohort (22% to 13% P < 0.05), which correlated with the shift
      towards outpatient treatment of consolidation cycles. A shift from Gram-negative
      to Gram-positive organisms as the cause of septicemia was also detected in the
      outpatient cohort, likely due to the introduction of ciprofloxacin prophylaxis.
      No significant emerging resistance and no septicemia-related mortality were noted
      in the outpatient cohort. CONCLUSION: The observed decrease in the incidence of
      septicemia in the ambulatory cohort adds supportive evidence to the feasibility
      of selective outpatient management of AML patients with respect to infectious
      complications.

PMID- 17442663
TI  - Toward a checklist for exchange and interpretation of data from a toxicology
      study.
AB  - Data from toxicology and toxicogenomics studies are valuable, and can be combined
      for meta-analysis using public data repositories such as Chemical Effects in
      Biological Systems Knowledgebase, ArrayExpress, and Gene Expression Omnibus. In
      order to fully utilize the data for secondary analysis, it is necessary to have a
      description of the study and good annotation of the accompanying data. This study
      annotation permits sophisticated cross-study comparison and analysis, and allows
      data from comparable subjects to be identified and fully understood. The Minimal
      Information About a Microarray Experiment Standard was proposed to permit
      deposition and sharing of microarray data. We propose the first step toward an
      analogous standard for a toxicogenomics/toxicology study, by describing a
      checklist of information that best practices would suggest be included with the
      study data. When the information in this checklist is deposited together with the
      study data, the checklist information helps the public explore the study data in
      context of time, or identify data from similarly treated subjects, and also
      explore/identify potential sources of experimental variability. The proposed
      checklist summarizes useful information to include when sharing study data for
      publication, deposition into a database, or electronic exchange with
      collaborators. It is not a description of how to carry out an experiment, but a
      definition of how to describe an experiment. It is anticipated that once a
      toxicology checklist is accepted and put into use, then toxicology databases can
      be configured to require and output these fields, making it straightforward to
      annotate data for interpretation by others.

PMID- 17442664
TI  - Microsomal expoxide hydrolase is required for 7,12-dimethylbenz[a]anthracene
      (DMBA)-induced immunotoxicity in mice.
AB  - Microsomal epoxide hydrolase (mEH, EPHX1) is involved in the metabolism of
      chemicals to generate dihydrodiol intermediates in the presence of the cytochrome
      P450. We have previously shown that 7,12-dimethylbenz[a]anthracene (DMBA) can
      suppress both cell-mediated and humoral immune responses in wild-type (WT)
      C57BL/6N mice but not in CYP1B1 null mice. In the present studies, we
      hypothesized the critical metabolite responsible for DMBA-induced immunotoxicity
      is likely to be the 3,4-dihydrodiol-1,2-epoxide metabolite of DMBA, which
      requires mEH for formation. Mice were gavaged orally with DMBA (0, 17, 50, and
      150 mg/kg) once a day for 5 days. Immune function and other assays were performed
      on day 7. Our data showed that unlike WT mice, DMBA treatment of mEH null mice
      produced no alterations in the body weight, spleen weight, or spleen cellularity.
      Similarly, DMBA treatments did not affect the PFC response in mEH null mice.
      Natural killer activity was not altered by DMBA treatment in mEH null mice. T
      cell mitogenesis was partially suppressed by 50 and 150 mg/kg DMBA treatments of
      mEH null mice, but B-cell mitogenesis was not affected. Finally, we assessed the
      biodistribution of DMBA in both C57BL/6N WT and mEH null mice in spleen, thymus,
      and liver after 24 h and 7 days oral gavage. The concentrations of DMBA in each
      organ were not significantly different in WT and in mEH null mice. Collectively,
      these results demonstrate that mEH (EPHX1 gene) is a crucial enzyme for metabolic
      activation of DMBA in vivo leading to immunosuppression of spleen cells.

PMID- 17442665
TI  - Interorganelle trafficking of ceramide is regulated by phosphorylation-dependent
      cooperativity between the PH and START domains of CERT.
AB  - The synthesis and transport of lipids are essential events for membrane
      biogenesis. However, little is known about how intracellular trafficking of
      lipids is regulated. Ceramide is synthesized at the endoplasmic reticulum (ER)
      and transported by the ceramide transfer protein CERT to the Golgi apparatus,
      where it is converted to sphingomyelin. CERT has a phosphoinositide-binding
      pleckstrin homology (PH) domain for Golgi-targeting and a lipid transfer START
      domain for intermembrane transfer of ceramide. We here show that CERT receives
      multiple phosphorylations at a serine-repeat motif, a possibe site for casein
      kinase I, and that the phosphorylation down-regulates the ER-to-Golgi transport
      of ceramide. In vitro assays show that the phosphorylation induces an
      autoinhibitory interaction between the PH and START domains and consequently
      inactivates both the phosphoinositide binding and ceramide transfer activities of
      CERT. Loss of sphingomyelin and cholesterol from cells causes dephosphorylation
      of CERT to activate it. The cooperative control of functionally distinct domains
      of CERT is a novel molecular event to regulate the intracellular trafficking of
      ceramide.

PMID- 17442666
TI  - Comparative analysis of two UDP-glucose dehydrogenases in Pseudomonas aeruginosa
      PAO1.
AB  - UDP-glucose dehydrogenase (UGDH) catalyzes a two-step NAD(+)-dependent oxidation
      of UDP-glucose to produce UDP-glucuronic acid, which is a common substrate for
      the biosynthesis of exopolysaccharide. Searching the Pseudomonas aeruginosa PAO1
      genome data base for a UGDH has helped identify two open reading frames, PA2022
      and PA3559, which may encode a UGDH. To elucidate their enzymatic identity, the
      two genes were cloned and overexpressed in Escherichia coli, and the recombinant
      proteins were purified. Both the gene products are active as dimers and are
      capable of utilizing UDP-glucose as a substrate to generate UDP-glucuronic acid.
      The K(m) values of PA2022 and PA3559 for UDP-glucose are approximately 0.1 and
      0.4 mM, whereas the K(m) values for NAD(+) are 0.5 and 2.0 mM, respectively.
      Compared with PA3559, PA2022 exhibits broader substrate specificity, utilizing
      TDP-glucose and UDP-N-acetylglucosamine with one-third the velocity of that with
      UDP-glucose. The PA2022 mutant and PA2022-PA3559 double mutant, but not the
      PA3559 mutant, are more susceptible to chloramphenicol, cefotaxime, and
      ampicillin. The PA3559 mutant, however, shows a reduced resistance to polymyxin B
      compared with wild type PAO1. Finally, real time PCR analysis indicates that
      PA3559 is expressed primarily in low concentrations of Mg(2+), which contrasts
      with the constitutive expression of PA2022. Although both the enzymes catalyze
      the same reaction, their enzymatic properties and gene expression profiles
      indicate that they play distinct physiological roles in P. aeruginosa, as
      reflected by different phenotypes displayed by the mutants.

PMID- 17442667
TI  - Subcellular localization and physiological significance of intracellular mannan
      binding protein.
AB  - Mannan-binding protein (MBP) is a C-type mammalian lectin specific for mannose
      and N-acetylglucosamine. MBP is mainly synthesized in the liver and occurs
      naturally in two forms, serum MBP (S-MBP) and intracellular MBP (I-MBP). S-MBP
      activates complement in association with MBP-associated serine proteases via the
      lectin pathway. Despite our previous study (Mori, K., Kawasaki, T., and
      Yamashina, I. (1984) Arch. Biochem. Biophys. 232, 223-233), the subcellular
      localization of I-MBP and its functional implication have not been clarified yet.
      Here, as an extension of our previous studies, we have demonstrated that the
      expression of human MBP cDNA reproduces native MBP differentiation of S-MBP and I
      MBP in human hepatoma cells. I-MBP shows distinct accumulation in cytoplasmic
      granules, and is predominantly localized in the endoplasmic reticulum (ER) and
      involved in COPII vesicle-mediated ER-to-Golgi transport. However, the
      subcellular localization of either a mutant (C236S/C244S) I-MBP, which lacks
      carbohydrate-binding activity, or the wild-type I-MBP in tunicamycin-treated
      cells shows an equally diffuse cytoplasmic distribution, suggesting that the
      unique accumulation of I-MBP in the ER and COPII vesicles is mediated by an N
      glycan-lectin interaction. Furthermore, the binding of I-MBP with glycoprotein
      intermediates occurs in the ER, which is carbohydrate- and pH-dependent, and is
      affected by glucose-trimmed high-mannose-type oligosaccharides. These results
      strongly indicate that I-MBP may function as a cargo transport lectin
      facilitating ER-to-Golgi traffic in glycoprotein quality control.

PMID- 17442668
TI  - Expression and mechanism of spleen tyrosine kinase activation by angiotensin II
      and its implication in protein synthesis in rat vascular smooth muscle cells.
AB  - Syk, a 72-kDa tyrosine kinase, is involved in development, differentiation, and
      signal transduction of hematopoietic and some non-hematopoietic cells. This study
      determined if Syk is expressed in vascular smooth muscle cells (VSMC) and
      contributes to angiotensin II (Ang II) signaling and protein synthesis. Syk was
      found in VSMC and was phosphorylated by Ang II through AT1 receptor. Ang II
      induced Syk phosphorylation was inhibited by piceatannol and dominant negative
      but not wild type Syk mutant. Syk phosphorylation by Ang II was attenuated by
      cytosolic phospholipase A(2) (cPLA(2)) inhibitor pyrrolidine-1 and retrovirus
      carrying small interfering RNAs (shRNAs) of this enzyme. Arachidonic acid (AA)
      increased Syk phosphorylation, and AA- and Ang II-induced phosphorylation was
      diminished by inhibitors of AA metabolism (5,8,11,14-eicosatetraynoic acid) and
      lipoxygenase (LO; baicalein) but not cyclooxygenase (indomethacin). AA
      metabolites formed via LO, 5(S)-, 12(S)-, and 15(S)-hydroxyeicosatetraenoic
      acids, which activate p38 MAPK, increased Syk phosphorylation. p38 MAPK inhibitor
      SB202190, and dominant negative p38 MAPK mutant attenuated Ang II- and AA-induced
      Syk phosphorylation. Adenovirus dominant negative c-Src mutant abolished Ang II -
      and AA-induced Syk phosphorylation and SB202190, and dominant negative p38 MAPK
      mutant inhibited Ang II-induced c-Src phosphorylation. Syk dominant negative
      mutant but not epidermal growth factor receptor blocker AG1478 also inhibited Ang
      II-induced VSMC protein synthesis. These data suggest that Syk expressed in VSMC
      is activated by Ang II through p38 MAPK-activated c-Src subsequent to cytosolic
      phospholipase A(2) and generation of AA metabolites via LO, and it mediates Ang
      II-induced protein synthesis independent of epidermal growth factor receptor
      transactivation (Ang II --> cPLA(2) --> AA metabolites of LO --> p38 MAPK --> c
      Src --> Syk --> protein synthesis).

PMID- 17442669
TI  - Tissue-specific autophagy alterations and increased tumorigenesis in mice
      deficient in Atg4C/autophagin-3.
AB  - Atg4C/autophagin-3 is a member of a family of cysteine proteinases proposed to be
      involved in the processing and delipidation of the mammalian orthologues of yeast
      Atg8, an essential component of an ubiquitin-like modification system required
      for execution of autophagy. To date, the in vivo role of the different members of
      this family of proteinases remains unclear. To gain further insights into the
      functional relevance of Atg4 orthologues, we have generated mutant mice deficient
      in Atg4C/autophagin-3. These mice are viable and fertile and do not display any
      obvious abnormalities, indicating that they are able to develop the autophagic
      response required during the early neonatal period. However, Atg4C-/--starved
      mice show a decreased autophagic activity in the diaphragm as assessed by
      immunoblotting studies and by fluorescence microscopic analysis of samples from
      Atg4C-/- GFP-LC3 transgenic mice. In addition, animals deficient in Atg4C show an
      increased susceptibility to develop fibrosarcomas induced by chemical
      carcinogens. Based on these results, we propose that Atg4C is not essential for
      autophagy development under normal conditions but is required for a proper
      autophagic response under stressful conditions such as prolonged starvation. We
      also propose that this enzyme could play an in vivo role in events associated
      with tumor progression.

PMID- 17442670
TI  - Activation of bestrophin Cl- channels is regulated by C-terminal domains.
AB  - Bestrophins (VMD2, VMD2L1, VMD2L2, and VMD2L3) are a new family of anion
      channels. The mechanisms of their regulation are not yet well understood.
      Recently, we found that a domain (amino acids 356-364) in the C terminus of mouse
      VMD2L3 (mBest3) inhibited channel activity when it was expressed in HEK293 cells
      (Qu, Z., Cui, Y., and Hartzell, H. C. (2006) FEBS Lett. 580, 2141-2214). Here we
      show that this auto-inhibitory (AI) domain in mBest3 and human (h)Best3 is
      composed of seven critical residues, (356)IPSFLGS(362). Replacement of any
      residue (except Pro(357)) in the domain with alanine activated Cl(-) currents.
      Substitution of Pro(357) with other amino acids, especially phenylalanine, did
      activate currents. Membrane biotinylation demonstrated that nonfunctional mBest3
      protein was trafficked to the plasma membrane, implying that the AI domain
      inhibited channel gating but not trafficking. mBest3-F359A and hBest3-G361A
      mutations induced outwardly rectifying currents, suggesting that the AI domain is
      associated with the channel pore or gating mechanism. Supporting this suggestion,
      the mBest3 AI domain was demonstrated to be located within a membrane-associated
      region. When the wild-type mBest3 C terminus (amino acids 292-669) was expressed
      in HEK293 cells, the protein was located mainly in the particulate fraction, but
      it became soluble when a sequence containing the AI domain was deleted (Delta353
      404). There is an AI domain ((357)QPSFQGS(363)) in mouse VMD2L1 (mBest2) as well,
      but its inhibitory effect is competed by a downstream facilitatory sequence
      (amino acids 405-454). These results suggest that an auto-inhibitory mechanism in
      C termini may be universal among bestrophins investigated in the study.

PMID- 17442671
TI  - Structure of amidase from Pseudomonas aeruginosa showing a trapped acyl transfer
      reaction intermediate state.
AB  - Microbial amidases belong to the thiol nitrilases family and have potential
      biotechnological applications in chemical and pharmaceutical industries as well
      as in bioremediation. The amidase from Pseudomonas aeruginosa isa6 x 38-kDa
      enzyme that catalyzes the hydrolysis of a small range of short aliphatic amides.
      The hereby reported high resolution crystallographic structure shows that each
      amidase monomer is formed by a globular four-layer alphabetabetaalpha sandwich
      domain with an additional 81-residue long C-terminal segment. This wraps arm-in
      arm with a homologous C-terminal chain of another monomer, producing a strongly
      packed dimer. In the crystal, the biological active homo-hexameric amidase is
      built grouping three such dimers around a crystallographic 3-fold axis. The
      structure also elucidates the structural basis for the enzyme activity, with the
      nitrilases catalytic triad at the bottom of a 13-A deep, funnel-shaped pocket,
      accessible from the solvent through a narrow neck with 3-A diameter. An acyl
      transfer intermediate, resulting from the purification protocol, was found bound
      to the amidase nucleophilic agent, Cys(166). These results suggest that some
      pocket defining residues should undergo conformational shifts to allow substrates
      and products to access and leave the catalytic pocket, for turnover to occur.

PMID- 17442672
TI  - Hypotonic activation of short ClC3 isoform is modulated by direct interaction
      between its cytosolic C-terminal tail and subcortical actin filaments.
AB  - Short ClC3 isoform (sClC3) functions as a volume-sensitive outwardly rectifying
      anion channel (VSOAC) in some cell types. In previous studies, we have shown that
      the hypotonic activation of sClC3 is linked to cell swelling-mediated remodeling
      of the actin cytoskeleton. In the present study, we have tested the hypothesis
      that the cytosolic tails of sClC3 bind to actin directly and that binding
      modulates the hypotonic activation of the channel. Co-sedimentation assays in
      vitro demonstrated a strong binding between the glutathione S-transferase-fused
      cytosolic C terminus of sClC3 (GST-sClC3-CT) to filamentous actin (F-actin) but
      not to globular monomeric actin (G-actin). The GST-fused N terminus (GST-sClC3
      NT) exhibited low binding affinity to both G- and F-actin. Co-sedimentation
      experiments with progressively truncated GST-sClC3-CT indicated that the F-actin
      binding region is located between amino acids 690 and 760 of sClC3. Two synthetic
      peptides mapping basic clusters of the cytosolic sClC3-CT (CTP2, isoleucine 716
      to leucine 734; and CTP3, proline 688 to proline 709) prevented binding of GST
      sClC3-CT to F-actin in vitro. Dialysis into NIH/3T3 cells of these two peptides
      (but not of synthetic peptide CTP1 (isoleucine 737 to glutamine 748)) reduced the
      maximal current density by 60 and 38%, respectively. Based on these results, we
      have concluded that, by direct interaction with subcortical actin filaments,
      sClC3 contributes to the hypotonic stress-induced VSOACs in NIH/3T3 cells.

PMID- 17442673
TI  - Identification of a gastrin response element in the vesicular monoamine
      transporter type 2 promoter and requirement of 20 S proteasome subunits for
      transcriptional activity.
AB  - Vesicular monoamine transporter type 2 (VMAT2) is crucial for accumulation of
      monoamine neurotranmitters into neuronal secretory vesicles and histamine into
      secretory granules of the enterochromaffin-like cell in the acid-secreting
      gastric mucosa. Gastric VMAT2 expression is regulated by the antral hormone
      gastrin acting at the CCK(2) receptor. We demonstrate a gastrin response element
      (-56)ccgccccctc(-47) in the proximal VMAT2 promoter that binds in a gastrin
      sensitive manner to nuclear proteins from gastric epithelial cell lines.
      Mutations within this sequence prevented nuclear protein binding and
      significantly reduced gastrin-stimulated expression of VMAT2 promoter-reporter
      constructs in gastric epithelial cells. In a yeast one-hybrid screen of an AR42J
      cell cDNA library, using the gastrin response element as bait, we identified a
      beta subunit of the 20 S proteasome, PSMB1, as a potential binding partner. In
      supershift assays, antibodies to PSMB1 and other proteasome beta subunits
      disrupted gastrin sensitive nuclear protein binding to the VMAT2 promoter.
      Moreover, RNA interference of PSMB1 significantly inhibited gastrin-mediated
      VMAT2 transcription. These data suggest that elements of the 20 S proteasome
      interact with the VMAT2 promoter to enhance G-protein-coupled receptor-mediated
      transcription.

PMID- 17442674
TI  - The non-mevalonate pathway of isoprenoid precursor biosynthesis.
AB  - The recently discovered non-mevalonate biosynthetic route to isoprenoid
      precursors is an essential metabolic pathway in plants, apicomplexan parasites,
      and many species of bacteria. The pathway relies on eight enzymes exploiting
      different cofactors and metal ions. Structural and mechanistic data now exist for
      most components of the pathway though there remain some gaps in our knowledge.
      The individual enzymes represent new, validated targets for broad spectrum
      antimicrobial drug and herbicide development. Detailed knowledge of the pathway
      may also be exploited to genetically modify microorganisms and plants to produce
      compounds of agricultural and medical interest.

PMID- 17442675
TI  - The tautomeric half-reaction of BphD, a C-C bond hydrolase. Kinetic and
      structural evidence supporting a key role for histidine 265 of the catalytic
      triad.
AB  - BphD of Burkholderia xenovorans LB400 catalyzes an unusual C-C bond hydrolysis of
      2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) to afford benzoic acid and
      2-hydroxy-2,4-pentadienoic acid (HPD). An enol-keto tautomerization has been
      proposed to precede hydrolysis via a gem-diol intermediate. The role of the
      canonical catalytic triad (Ser-112, His-265, Asp-237) in mediating these two half
      reactions remains unclear. We previously reported that the BphD-catalyzed
      hydrolysis of HOPDA (lambda(max) is 434 nm for the free enolate) proceeds via an
      unidentified intermediate with a red-shifted absorption spectrum (lambda(max) is
      492 nm) (Horsman, G. P., Ke, J., Dai, S., Seah, S. Y. K., Bolin, J. T., and
      Eltis, L. D. (2006) Biochemistry 45, 11071-11086). Here we demonstrate that the
      S112A variant generates and traps a similar intermediate (lambda(max) is 506 nm)
      with a similar rate, 1/tau approximately 500 s(-1). The crystal structure of the
      S112A:HOPDA complex at 1.8-A resolution identified this intermediate as the keto
      tautomer, (E)-2,6-dioxo-6-phenyl-hex-3-enoate. This keto tautomer did not
      accumulate in either the H265A or the S112A/H265A double variants, indicating
      that His-265 catalyzes tautomerization. Consistent with this role, the wild type
      and S112A enzymes catalyzed tautomerization of the product HPD, whereas H265A
      variants did not. This study thus identifies a keto intermediate, and
      demonstrates that the catalytic triad histidine catalyzes the tautomerization
      half-reaction, expanding the role of this residue from its purely hydrolytic
      function in other serine hydrolases. Finally, the S112A:HOPDA crystal structure
      is more consistent with hydrolysis occurring via an acyl-enzyme intermediate than
      a gem-diol intermediate as solvent molecules have poor access to C6, and the
      closest ordered water is 7 A away.

PMID- 17442676
TI  - Movements of the TolR C-terminal domain depend on TolQR ionizable key residues
      and regulate activity of the Tol complex.
AB  - The TolQRA proteins of Escherichia coli form an inner membrane complex involved
      in the maintenance of the outer membrane stability and in the late stages of cell
      division. The TolQR complex uses the proton-motive force to regulate TolA
      conformation and its interaction with the outer membrane Pal lipoprotein. It has
      been proposed that an ion channel forms at the TolQR transmembrane helix
      interface. This complex assembles with a minimal TolQ/TolR ratio of 4:2,
      therefore involving at least 14 transmembrane helices, which may form the ion
      pathway. The C-terminal periplasmic domain of TolR protein interacts with TolQ
      and has been proposed to control the TolQR channel activity. Here, we constructed
      unique cysteine substitutions in the last 27 residues of TolR. Each of the
      substitutions results in a functional TolR protein. Disulfide cross-linking
      demonstrates that the TolQR complex is dynamic, involving conformational
      modifications of TolR C-terminal domain. We monitored these structural changes by
      cysteine accessibility experiments and showed that the conformation of this
      domain is responsive to the proton-motive force and on the presence of critical
      residues of the ion pathway.

PMID- 17442677
TI  - Biogenesis of a respiratory complex is orchestrated by a single accessory
      protein.
AB  - The biogenesis of respiratory complexes is a multistep process that requires
      finely tuned coordination of subunit assembly, metal cofactor insertion, and
      membrane-anchoring events. The dissimilatory nitrate reductase of the bacterial
      anaerobic respiratory chain is a membrane-bound heterotrimeric complex nitrate
      reductase A (NarGHI) carrying no less than eight redox centers. Here, we
      identified different stable folding assembly intermediates of the nitrate
      reductase complex and analyzed their redox cofactor contents using electron
      paramagnetic resonance spectroscopy. Upon the absence of the accessory protein
      NarJ, a global defect in metal incorporation was revealed. In addition to the
      molybdenum cofactor, we show that NarJ is required for specific insertion of the
      proximal iron-sulfur cluster (FS0) within the soluble nitrate reductase (NarGH)
      catalytic dimer. Further, we establish that NarJ ensures complete maturation of
      the b-type cytochrome subunit NarI by a proper timing for membrane anchoring of
      the NarGH complex. Our findings demonstrate that NarJ has a multifunctional role
      by orchestrating both the maturation and the assembly steps.

PMID- 17442678
TI  - Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium.
AB  - Tight junctions play a key role in mediating paracellular ion reabsorption in the
      kidney. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC)
      is a human disorder caused by mutations in the tight junction protein claudin-16.
      However, the molecular mechanisms underlining the renal handling of magnesium and
      its dysfunction causing FHHNC are unknown. Here we show that claudin-16 plays a
      key role in maintaining the paracellular cation selectivity of the thick
      ascending limbs of the nephron. Using RNA interference, we have generated claudin
      16-deficient mouse models. Claudin-16 knock-down (KD) mice exhibit chronic renal
      wasting of magnesium and calcium and develop renal nephrocalcinosis. Our data
      suggest that claudin-16 forms a non-selective paracellular cation channel, rather
      than a selective Mg(2+)/Ca(2+) channel as previously proposed. Our study
      highlights the pivotal importance of the tight junction in renal control of ion
      homeostasis and provides answer to the pathogenesis of FHHNC. We anticipate our
      study to be a starting point for more sophisticated in vivo analysis of tight
      junction proteins in renal functions. Furthermore, tight junction proteins could
      be major targets of drug development for electrolyte disorders.

PMID- 17442679
TI  - Identification of the sites for CaMK-II-dependent phosphorylation of GABA(A)
      receptors.
AB  - Phosphorylation can affect both the function and trafficking of GABA(A) receptors
      with significant consequences for neuronal excitability. Serine/threonine kinases
      can phosphorylate the intracellular loops between M3-4 of GABA(A) receptor beta
      and gamma subunits thereby modulating receptor function in heterologous
      expression systems and in neurons (1, 2). Specifically, CaMK-II has been
      demonstrated to phosphorylate the M3-4 loop of GABA(A) receptor subunits
      expressed as GST fusion proteins (3, 4). It also increases the amplitude of
      GABA(A) receptor-mediated currents in a number of neuronal cell types (5-7). To
      identify which substrate sites CaMK-II might phosphorylate and the consequent
      functional effects, we expressed recombinant GABA(A) receptors in NG108-15 cells,
      which have previously been shown to support CaMK-II modulation of GABA(A)
      receptors containing the beta3 subunit (8). We now demonstrate that CaMK-II
      mediates its effects on alpha1beta3 receptors via phosphorylation of Ser(383)
      within the M3-4 domain of the beta subunit. Ablation of beta3 subunit
      phosphorylation sites for CaMK-II revealed that for alphabetagamma receptors,
      CaMK-II has a residual effect on GABA currents that is not mediated by previously
      identified sites of CaMK-II phosphorylation. This residual effect is abolished by
      mutation of tyrosine phosphorylation sites, Tyr(365) and Tyr(367), on the gamma2S
      subunit, and by the tyrosine kinase inhibitor genistein. These results suggested
      that CaMK-II is capable of directly phosphorylating GABA(A) receptors and
      activating endogenous tyrosine kinases to phosphorylate the gamma2 subunit in
      NG108-15 cells. These findings were confirmed in a neuronal environment by
      expressing recombinant GABA(A) receptors in cerebellar granule neurons.

PMID- 17442680
TI  - Negative elongation factor NELF represses human immunodeficiency virus
      transcription by pausing the RNA polymerase II complex.
AB  - Human immunodeficiency virus (HIV) transcription requires virally encoded Tat and
      the P-TEFb protein complex, which together associate with the Tat-activating
      region, a structured region in the nascent transcript. P-TEFb phosphorylates
      Proteins in the transcription elongation complex, including RNA polymerase II
      (pol II), to stimulate elongation and to overcome premature termination. However,
      the status of the elongation complex on the HIV long terminal repeat (LTR) in a
      repressed state is not known. Chromatin immunoprecipitation demonstrated that
      NELF, a negative transcription elongation factor, was associated with the LTR.
      Depleting NELF increased processive HIV transcription and replication. Mapping
      pol II on the LTR showed that pol II was paused and that NELF depletion released
      pol II. Decreasing NELF also correlated with displacement of a positioned
      nucleosome and increased acetylation of histone H4, suggesting coupling of
      transcription elongation and chromatin remodeling. Previous work has indicated
      that the Tat-activating region plays a critical role in regulating transcription
      from the LTR. Our results reveal an earlier stage, mediated by NELF, when
      repression occurs at the HIV LTR.

PMID- 17442681
TI  - Caffeine accelerates absorption and enhances the analgesic effect of
      acetaminophen.
AB  - The aim of this study was to determine the analgesic effect of acetaminophen
      compared to a combination of both caffeine and acetaminophen or caffeine alone
      using tonic and phasic pain stimulation. Twenty-four subjects were treated orally
      with 1000 mg acetaminophen, 130 mg caffeine, and a combination of both in a 4-way
      crossover, double-blind, placebo-controlled study. Pharmacokinetics and analgesic
      effects were assessed by means of an experimental pain model based on pain
      related cortical potentials after phasic stimulation of the nasal mucosa with
      CO(2) and based on pain ratings after tonic stimulation with dry air. Analgesic
      effects of acetaminophen and acetaminophen plus caffeine but not caffeine alone
      caused a significant reduction of pain-related cortical potentials beginning 30
      minutes after medication. The combination demonstrated an enhanced effect
      throughout the observation time up to 3 hours. Caffeine accelerated acetaminophen
      absorption, indicated by enhanced early AUCs. Significant analgesic effects of
      the combination on tonic pain ratings were found throughout the observation time
      as compared to acetaminophen and placebo. In this study, caffeine enhanced and
      prolonged the analgesic activity of acetaminophen.

PMID- 17442682
TI  - Biologics in the pipeline: large molecules with high hopes or bigger risks?

PMID- 17442683
TI  - Nuclear receptors and the regulation of drug-metabolizing enzymes and drug
      transporters: implications for interindividual variability in response to drugs.
AB  - Erratic or unpredictable response to drugs remains a challenge of modern drug
      therapy. An important determinant of such interindividual differences in drug
      response is variability in the expression of drug-metabolizing enzymes and/or
      transporters at sites of absorption and/or tissue distribution. Variable drug
      metabolizing enzyme and transporter expression can result in unpredictable
      exposure and tissue distribution of drugs and may manifest as adverse effects or
      therapeutic failure. In the past decade, important new insights have been made
      relating to the regulatory mechanisms governing the expression of drug
      metabolizing enzymes and transporters by ligand-activated nuclear receptors.
      Specifically, there is compelling evidence to demonstrate that PXR, CAR, FXR,
      LXR, VDR, HNF4alpha, and AhR form a battery of nuclear receptors that regulate
      the expression of many important drug-metabolizing enzyme and transporters. In
      this review, the authors focus on clinically important drug-metabolizing enzymes
      such as CYP3A4, CYP2B6, CYP2C9, CYP2C19, UGT1A1, SULT2A1, and glutathione S
      transferases and their regulation by nuclear receptors. They also review the
      nuclear receptor-mediated regulation of drug transporters such as MDR1, MRP2,
      MRP4, BSEP, BCRP, NTCP, OATP1B3, and OATP1A2. Finally, they outline how the drug
      development process has been affected by the current understanding of the
      involvement of nuclear receptors in the regulation of drug disposition genes.

PMID- 17442684
TI  - Molecular pharmacokinetics of catharanthus (vinca) alkaloids.
AB  - This review focuses on the published data regarding the molecular determinants
      (enzymes, transporters, orphan nuclear receptors) of Catharanthus (vinca)
      alkaloids pharmacokinetics in humans. The clinical impact of these determinants
      (drug disposition, drug-drug interactions) is also discussed.

PMID- 17442685
TI  - AAPS-FDA Workshop White Paper: microdialysis principles, application, and
      regulatory perspectives.

PMID- 17442686
TI  - Effect of clopidogrel on the steady-state pharmacokinetics of fluvastatin.
AB  - This study assessed the effects of clopidogrel, a CYP 2C9 inhibitor, on
      fluvastatin pharmacokinetics in healthy volunteers. The effects of combined
      clopidogrel-fluvastatin treatment on platelet function were also determined.
      Subjects received 80 mg fluvastatin (extended-release formulation) alone on days
      1 through 9, 80 mg fluvastatin and 300 mg clopidogrel (loading dose) on day 10,
      and 80 mg fluvastatin and 75 mg clopidogrel (maintenance dose) on days 11 through
      19. Compared to treatment with fluvastatin alone, fluvastatin AUC was similar and
      C(max) increased marginally (15.7%) with concomitant treatment with clopidogrel.
      Platelet aggregation was inhibited by clopidogrel by 33% two hours after the
      loading dose and by 47% at steady state, similar to that reported for clopidogrel
      alone treatment. The authors conclude that coadministration of fluvastatin and
      clopidogrel has no clinically relevant effect on fluvastatin pharmacokinetics or
      on platelet inhibition by clopidogrel.

PMID- 17442687
TI  - The effect of etoricoxib on the pharmacodynamics and pharmacokinetics of
      warfarin.
AB  - The effects of etoricoxib on pharmacodynamic and pharmacokinetic parameters of
      warfarin were determined in healthy men and women. Subjects titrated with
      warfarin to an international normalized ratio for prothrombin time of 1.4 to 1.7
      during a 28-day prestudy period were randomly assigned in crossover fashion to be
      coadministered etoricoxib (120 mg) or matching placebo over two 21-day continuous
      periods. On day 21, a 24-hour pharmacokinetic profile of both S(-) and R(+)
      warfarin, as well as international normalized ratio values, were determined.
      Etoricoxib increased the international normalized ratio by 13% (90% confidence
      interval: 8%, 19%; P </= .001). Etoricoxib had no effect on the pharmacokinetics
      of S(-) warfarin but led to a modest increase in the AUC(24 h) ( approximately
      10%) of R(+) warfarin. This increase in the international normalized ratio is not
      likely to be clinically important in most patients; however, the international
      normalized ratio of patients coadministered oral anticoagulants and etoricoxib
      should be closely monitored, particularly during initiation of therapy.

PMID- 17442688
TI  - Pharmacodynamics of vildagliptin in patients with type 2 diabetes during OGTT.
AB  - This randomized, open-label, placebo-controlled, 7-period crossover study
      assessed dose-response relationships following single oral doses (10-400 mg) of
      vildagliptin in 16 patients with type 2 diabetes mellitus. Plasma levels of
      parent drug, dipeptidyl peptidase-4 activity, glucose, insulin, and glucagon were
      measured during 75-g oral glucose tolerance tests performed after an overnight
      fast, 30 minutes after drug administration. The t(max) for parent drug was
      observed between 0.5 and 1.5 hours postdose. Both C(max) and AUC(0-8 h) increased
      dose proportionately. Both onset and duration of dipeptidyl peptidase-4
      inhibition were dose dependent, but >90% inhibition occurred within 45 minutes
      and was maintained for >/=4 hours after each dose. Glucose excursions and
      glucagon levels during oral glucose tolerance tests were significantly and
      similarly decreased after each dose of vildagliptin, and insulin levels were
      significantly and similarly increased after each dose level. Unlike findings
      during mixed-meal challenges, vildagliptin increases plasma insulin levels during
      oral glucose tolerance tests in patients with type 2 diabetes mellitus.

PMID- 17442689
TI  - Smart textiles: a new drug delivery system for symptomatic treatment of a common
      cold.
AB  - Smart textiles provide the possibility of being coated with cineole, menthol, and
      camphor. Due to over-the-counter availability, ethereal oils are frequently used
      to treat a common cold. The existing pharmaceutical forms entail the risk of oral
      ingestion by children, which can cause severe intoxications. This risk could be
      limited by a smart textile application. Prior to applicability tests in children,
      the principal traceability of smart textile-applied ethereal oils at their site
      of action in the alveoli has to be demonstrated. Therefore, a crossover trial
      (ointment vs smart textiles) with 6 healthy volunteers was carried out as a proof
      of-concept study. As a result, the principle proof is given that smart textile
      applied ethereal oils are available at their site of action. Because of the
      volatility of the active ingredients, a close-fitting textile form has to be
      developed for further clinical development of smart textiles to achieve higher
      concentrations in the alveoli. Slower liberation properties and a more convenient
      skin sensation in comparison to available pharmaceutical forms may provide
      advantages for the applicability in both children and adults.

PMID- 17442690
TI  - Eosinophilic leukaemia.
AB  - The last few years have seen much progress in our understanding of, and
      treatments for, eosinophilic leukaemia. In preparing this review, we used Pubmed
      and the archives of well-known Haematology journals to search for relevant
      research papers and reviews published in the last 5-10 years. In this article, we
      review the differential diagnosis and sub-classification of eosinophilic
      leukaemia, and go on to discuss clinical features, investigation and treatment of
      these disorders. We are increasingly able to classify clonal eosinophilias based
      on the underlying molecular genetic abnormalities, and prognosticate and treat
      patients according to this. The successful treatment of certain of these patients
      with imatinib, followed by a greater understanding of the mechanism of this
      treatment, has revolutionized the outlook for many patients with eosinophilic
      leukaemia. New similar tyrosine kinase inhibitors and other promising therapies
      are on the horizon.

PMID- 17442691
TI  - The roles of age, gender, inhibitory control, and parental supervision in
      children's pedestrian safety.
AB  - OBJECTIVE: Thousands of American children are injured or killed each year as
      pedestrians, but behavioral factors in pedestrian injury etiology remain poorly
      understood. We examined the roles of children's individual differences (age,
      gender, and inhibitory control) and parental supervision in children's pedestrian
      behaviors. METHODS: Using the pretend road method, a sample of 85 children and 26
      adults crossed a pretend crosswalk set adjacent to a real road. Safety of
      crossing the pretend road was determined based on actual traffic on the real
      road. Adults also crossed the real road. RESULTS: Adults' behavior on the real
      road paralleled that on the pretend road, supporting validity of the method. On
      the pretend road, younger children, boys, and children with less behavioral
      control engaged in riskier pedestrian behaviors. Children with less behavioral
      control responded more noticeably to increases in parental supervision.
      CONCLUSION: Results are discussed in relation to children's development and
      injury prevention.

PMID- 17442692
TI  - Scholarly literature review: management of neurocognitive late effects with
      stimulant medication.
AB  - OBJECTIVE: To examine the extant literature on stimulant drug therapy for
      survivors of childhood cancer during the late-effects period. METHODS: A review
      of literature is provided on the mechanism of and cognitive toxicities for
      children and adolescents treated for acute lymphoblastic leukemia (ALL) and
      malignant brain tumors (BT) as well as the pharmacotherapy of stimulant
      medications, with a specific review of literature on the efficacy and safety of
      the stimulants for children with ALL and BT. RESULTS: Only four studies were
      found that have examined the effects of stimulant medication on the cognitive
      toxicities of childhood survivors of cancer during the late-effects period and
      only two of these investigations were controlled clinical trials. Findings
      suggest efficacy of the stimulants on parent and teacher ratings of attention and
      putative tasks of attention and executive functioning. CONCLUSIONS: Although
      there is some preliminary support for the efficacy and safety of the stimulants
      for survivors of ALL and BT, more research is needed concerning the long-term
      effects of the stimulants among cancer survivors.

PMID- 17442693
TI  - Brief report: parental report of sleep behaviors following moderate or severe
      pediatric traumatic brain injury.
AB  - OBJECTIVE: Determine the effect of moderate and severe traumatic brain injuries
      (TBI) on the sleep of school-aged children. METHODS: A concurrent cohort
      prospective design compared children aged 6-12 years who sustained moderate TBI
      (baseline n = 56), severe TBI (n = 53), or only orthopedic injuries (n = 80).
      Retrospective parental report of pre-injury sleep was collected about 3 weeks
      post-injury. Post-injury assessments occurred prospectively a mean of 6, 12, and
      48 months later. RESULTS: Growth curve analyses compared the groups over time.
      The moderate TBI group had worse pre-injury sleep than the other groups. The
      moderate TBI and orthopedic injury groups displayed a small decline in sleep
      problems from pre- to post-injury. Children with severe TBI displayed increased
      post-injury sleep problems. CONCLUSIONS: Children who sustain severe TBI are at
      elevated risk for post-injury sleep problems. Because sleep problems may result
      in daytime impairments and family distress, additional clinical and research
      attention is warranted.

PMID- 17442694
TI  - Risky driving in adolescents and young adults with childhood ADHD.
AB  - OBJECTIVE: To examine risky driving behaviors and negative driving outcomes in a
      large sample of adolescents and adults diagnosed in childhood with Attention
      Deficit Hyperactivity Disorder (ADHD) compared with demographically similar
      controls without ADHD. METHODS: 355 adolescents and young adults of the
      Pittsburgh ADHD Longitudinal Study (PALS) (n = 203 probands; n = 152 controls)
      were administered the Young Adult Driving Questionnaire. Parent and self-report
      of current ADHD symptoms and conduct problems were tested as potential mediators
      of the association between childhood ADHD and negative driving outcomes. RESULTS:
      ADHD group differences, of small to medium effect size, were found for number of
      tickets and accidents, and hyperactivity-impulsivity at follow-up emerged as a
      significant mediator of this association. Current conduct problems were
      associated with both risky and alcohol-impaired driving. CONCLUSIONS: Childhood
      ADHD elevates risk for driving-related problems, especially when symptoms
      persist. Co-occurring conduct problems capture some of this risk.

PMID- 17442695
TI  - Could using general health and longstanding limiting illness as a joint health
      outcome add to understanding in social inequalities research?

PMID- 17442696
TI  - How do parents' child-feeding behaviours influence child weight? Implications for
      childhood obesity policy.
AB  - BACKGROUND: Parents have some responsibility for children's dietary habits and
      they are often the focus of public health interventions designed to improve
      children's diets and thereby reduce the prevalence of childhood obesity. The
      current UK interventions promote awareness of healthy food choices, but offer
      little guidance for parents on child-feeding behaviours. METHODS: A review of
      recent literature regarding child-feeding behaviours and child weight. RESULTS:
      Parents report using a wide range of child-feeding behaviours, including
      monitoring, pressure to eat and restriction. Restriction of children's eating has
      most frequently and consistently been associated with child weight gain.
      Furthermore, there is substantial evidence for a causal relationship between
      parental restriction and childhood overweight. CONCLUSIONS: Parents may
      inadvertently promote excess weight gain in childhood by using inappropriate
      child-feeding behaviours. We recommend the development of interventions to
      increase awareness of the possible consequences of inappropriate child-feeding
      behaviours. Parents who are concerned about their child's weight will also
      require guidance and support in order to adopt more appropriate child-feeding
      behaviours.

PMID- 17442697
TI  - Tailbud-derived mesenchyme promotes urinary tract segmentation via BMP4
      signaling.
AB  - Urinary tract morphogenesis requires the sub-division of the ureteric bud (UB)
      into the intra-renal collecting system and ureter, two tissues with unique
      structural and functional properties. In this report we investigate the cellular
      and molecular mechanisms that mediate their differentiation. Fate mapping
      experiments in the developing chick indicate that the UB is surrounded by two
      distinct mesenchymal populations: nephrogenic mesenchyme derived from the
      intermediate mesoderm and tailbud-derived mesoderm, which is selectively
      associated with the domain of the UB that differentiates into the ureter.
      Functional experiments utilizing murine metanephric kidney explants show that
      BMP4, a paracrine factor secreted by tailbud-derived mesenchyme, is required for
      ureter morphogenesis. Conversely, ectopic BMP4 signaling is sufficient to induce
      ureter morphogenesis in domains of the UB normally fated to differentiate into
      the intra-renal collecting system. Collectively, these results indicate that the
      border between the kidney and ureter forms where mesenchymal tissues originating
      in two different areas of the early embryo meet. These data raise the possibility
      that the susceptibility of this junction to congenital defects in humans, such as
      ureteral-pelvic obstructions, may be related to the complex morphogenetic
      movements that are required to integrate cells from these different lineages into
      a single functional structure.

PMID- 17442698
TI  - Na,K-ATPase alpha2 and Ncx4a regulate zebrafish left-right patterning.
AB  - A conserved molecular cascade involving Nodal signaling that patterns the
      laterality of the lateral mesoderm in vertebrates has been extensively studied,
      but processes involved in the initial break of left-right (LR) symmetry are just
      beginning to be explored. Here we report that Na,K-ATPase alpha2 and Ncx4a
      function upstream of Nodal signaling to regulate LR patterning in zebrafish.
      Knocking down Na,K-ATPase alpha2 and Ncx4a activity in dorsal forerunner cells
      (DFCs), which are precursors of Kupffer's vesicle (KV), is sufficient to disrupt
      asymmetric gene expression in the lateral plate mesoderm and randomize the
      placement of internal organs, indicating that the activity of Na,K-ATPase alpha2
      and Ncx4a in DFCs/KV is crucial for LR patterning. High-speed videomicroscopy and
      bead implantation experiments show that KV cilia are immobile and the directional
      fluid flow in KV is abolished in Na,K-ATPase alpha2 and Ncx4a morphants,
      suggesting their essential role in KV ciliary function. Furthermore, we found
      that intracellular Ca(2+) levels are elevated in Na,K-ATPase alpha2 and Ncx4a
      morphants and that the defects in ciliary motility, KV fluid flow and placement
      of internal organs induced by their knockdown could be suppressed by inhibiting
      the activity of Ca(2+)/calmodulin-dependent protein kinase II. Together, our data
      demonstrate that Na,K-ATPase alpha2 and Ncx4a regulate LR patterning by
      modulating intracellular calcium levels in KV and by influencing cilia function,
      revealing a previously unrecognized role for calcium signaling in LR patterning.

PMID- 17442699
TI  - A Dynein-dependent shortcut rapidly delivers axis determination transcripts into
      the Drosophila oocyte.
AB  - The primary axes of Drosophila are set up by the localization of transcripts
      within the oocyte. These mRNAs originate in the nurse cells, but how they move
      into the oocyte remains poorly understood. Here, we study the path and mechanism
      of movement of gurken RNA within the nurse cells and towards and through ring
      canals connecting them to the oocyte. gurken transcripts, but not control
      transcripts, recruit the cytoplasmic Dynein-associated co-factors Bicaudal D
      (BicD) and Egalitarian in the nurse cells. gurken RNA requires BicD and Dynein
      for its transport towards the ring canals, where it accumulates before moving
      into the oocyte. Our results suggest that bicoid and oskar transcripts are also
      delivered to the oocyte by the same mechanism, which is distinct from cytoplasmic
      flow. We propose that Dynein-mediated transport of specific RNAs along
      specialized networks of microtubules increases the efficiency of their delivery,
      over the flow of general cytoplasmic components, into the oocyte.

PMID- 17442700
TI  - Genomic characterization of Gli-activator targets in sonic hedgehog-mediated
      neural patterning.
AB  - Sonic hedgehog (Shh) acts as a morphogen to mediate the specification of distinct
      cell identities in the ventral neural tube through a Gli-mediated (Gli1-3)
      transcriptional network. Identifying Gli targets in a systematic fashion is
      central to the understanding of the action of Shh. We examined this issue in
      differentiating neural progenitors in mouse. An epitope-tagged Gli-activator
      protein was used to directly isolate cis-regulatory sequences by chromatin
      immunoprecipitation (ChIP). ChIP products were then used to screen custom genomic
      tiling arrays of putative Hedgehog (Hh) targets predicted from transcriptional
      profiling studies, surveying 50-150 kb of non-transcribed sequence for each
      candidate. In addition to identifying expected Gli-target sites, the data
      predicted a number of unreported direct targets of Shh action. Transgenic
      analysis of binding regions in Nkx2.2, Nkx2.1 (Titf1) and Rab34 established these
      as direct Hh targets. These data also facilitated the generation of an algorithm
      that improved in silico predictions of Hh target genes. Together, these
      approaches provide significant new insights into both tissue-specific and general
      transcriptional targets in a crucial Shh-mediated patterning process.

PMID- 17442701
TI  - Notch signaling regulates neural precursor allocation and binary neuronal fate
      decisions in zebrafish.
AB  - Notch signaling plays a well-described role in regulating the formation of
      neurons from proliferative neural precursors in vertebrates but whether, as in
      flies, it also specifies sibling cells for different neuronal fates is not known.
      Ventral spinal cord precursors called pMN cells produce mostly motoneurons and
      oligodendrocytes, but recent lineage-marking experiments reveal that they also
      make astrocytes, ependymal cells and interneurons. Our own clonal analysis of pMN
      cells in zebrafish showed that some produce a primary motoneuron and KA'
      interneuron at their final division. We investigated the possibility that Notch
      signaling regulates a motoneuron-interneuron fate decision using a combination of
      mutant, transgenic and pharmacological manipulations of Notch activity. We show
      that continuous absence of Notch activity produces excess primary motoneurons and
      a deficit of KA' interneurons, whereas transient inactivation preceding
      neurogenesis results in an excess of both cell types. By contrast, activation of
      Notch signaling at the neural plate stage produces excess KA' interneurons and a
      deficit of primary motoneurons. Furthermore, individual pMN cells produce similar
      kinds of neurons at their final division in mib mutant embryos, which lack Notch
      signaling. These data provide evidence that, among some postmitotic daughters of
      pMN cells, Notch promotes KA' interneuron identity and inhibits primary
      motoneuron fate, raising the possibility that Notch signaling diversifies
      vertebrate neuron type by mediating similar binary fate decisions.

PMID- 17442702
TI  - Alcohol drinking, consumption patterns and breast cancer among Danish nurses: a
      cohort study.
AB  - BACKGROUND: The aim of this study was to analyse the impact of alcohol intake and
      drinking pattern on the risk of breast cancer. METHODS: A total of 17 647 nurses
      were followed from 1993 until the end of 2001. At baseline participants completed
      a questionnaire on alcohol intake and other lifestyle-related factors. Data were
      analysed using Cox's proportional hazard model. RESULTS: During follow-up 457
      women were diagnosed with breast cancer. The relative risk of breast cancer was
      2.30 [Confidence interval (CI): 1.56-3.39] for alcohol intake of 22-27 drinks per
      week, compared to 1-3 drinks per week. Among alcohol consumers, weekly alcohol
      intake increased the risk of breast cancer with 2% for each additional drink
      consumed. Weekend consumption increased the risk with 4% for each additional
      drink consumed friday through sunday. Binge drinking of 4-5 drinks the latest
      weekday increased risk with 55%, compared with consumption of one drink. A
      possible threshold in risk estimates was found for consumption above 27 drinks
      per week. CONCLUSIONS: For alcohol consumption above the intake most frequently
      reported, the risk of breast cancer is increased. The risk is minor for moderate
      levels but increases for each additional drink consumed during the week. Weekend
      consumption and binge drinking imply an additional increase in breast cancer
      risk.

PMID- 17442703
TI  - Rubella immune status of indigenous and immigrant pregnant women in Catalonia,
      Spain.
AB  - BACKGROUND: The objective of the study was to determine the prevalence of rubella
      antibodies in representative samples of pregnant women in Catalonia. METHODS: A
      representative sample of pregnant women in Catalonia was obtained by random
      sampling by clusters (hospitals with maternity units) stratified by provinces.
      Blood was obtained from the umbilical cord at childbirth in 1538 women (of whom
      308 were immigrants) and was tested for rubella antibodies by ELISA (Enzime
      linked immunosorbent assay). RESULTS: The global prevalence of antibodies was
      93.4% [95% confidence interval (CI): 93.3-93.5] and was significantly higher in
      indigenous women (94.9;95%CI:93.3-95.9) compared with immigrants [89.0; 95%CI:
      85.5-92.5 (P<0. 0001)] with crude Odds ratio (OR) of 2.15 (95%CI: 1.40-3.32).The
      prevalence was higher in women living in rural habitats (97%) and those in higher
      social classes (96.3%); OR 2.54 (95%CI: 1.22-5.30) and 2.17 (95%CI: 1.24-3.81),
      respectively. CONCLUSION: Fertile female immigrants from countries with no
      vaccination or where vaccination coverage is low should be actively approached
      for vaccination to reduce the risk of infection and congenital rubella.

PMID- 17442704
TI  - Mimicry of erythropoietin and interleukin-6 signalling by an antibody/cytokine
      receptor chimera in murine myeloid 32D cells.
AB  - We have previously designed antibody-cytokine receptor chimeras that could
      respond to a cognate antigen. While these chimeric receptors were functional, it
      has not been investigated exactly how they mimic signal transduction through
      corresponding wild-type receptors. In this study, we compared the growth
      properties and the phosphorylation status of intracellular signal transducers
      between the erythropoietin receptor (EpoR)- or gp130-based chimeric receptors and
      wild-type EpoR or EpoR-gp130 chimera, respectively. Expression plasmids, encoding
      V(H) or V(L) region of anti-hen egg lysozyme (HEL) antibody HyHEL-10 tethered to
      a pair of extracellular D2 domain of EpoR and transmembrane/cytoplasmic domains
      of either EpoR or gp130, were constructed, and pairs of chimeric receptor
      combinations (V(H)-EpoR and V(L)-EpoR, V(H)-gp130 and V(L)-gp130, V(H)-EpoR and
      V(L)-gp130, V(H)-gp130 and V(L)-EpoR) were expressed in an IL-3-dependent myeloid
      cell line, 32D. Growth assay revealed that the transfectants all grew in a HEL
      dependent manner. As for phosphorylation of Stat3, Stat5, ERK and Akt, the
      chimeric receptors showed similar activation pattern of signalling molecules with
      wild-type receptors, although the chimeric receptors showed ligand-independency
      and a little lower maximal phosphorylation than the corresponding wild-type
      receptors. The results demonstrate that antibody-receptor chimeras could
      substantially mimic wild-type receptors.

PMID- 17442705
TI  - Traffic exposure and lung function in adults: the Atherosclerosis Risk in
      Communities study.
AB  - BACKGROUND: Traffic exposure is a major contributor to ambient air pollution for
      people living close to busy roads. The relationship between traffic exposure and
      lung function remains inconclusive in adults. METHODS: A cross-sectional study
      was conducted to investigate the association between traffic exposure and lung
      function in the Atherosclerosis Risk in Communities (ARIC) study, a community
      based cohort of 15 792 middle aged men and women. Traffic density and distance to
      major roads were used as measures of traffic exposure. RESULTS: After controlling
      for potential confounders including demographic factors, personal and
      neighbourhood level socioeconomic characteristics, cigarette smoking and
      background air pollution, higher traffic density was significantly associated
      with lower forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)
      in women. Relative to the lowest quartile of traffic density, the adjusted
      differences across increasing quartiles were 5.1, -15.4 and -21.5 ml for FEV1 (p
      value of linear trend across the quartiles = 0.041) and 1.2, -23.4 and -34.8 ml
      for FVC (p trend = 0.010). Using distance from major roads as a simpler index of
      traffic related air pollution exposure, the FEV1 was -15.7 ml (95% CI -34.4 to
      2.9) lower and the FVC was -24.2 ml (95% CI -46.2 to -2.3) lower for women living
      within 150 m compared with subjects living further away. There was no significant
      effect of traffic density or distance to major roads on lung function in men. The
      FEV1/FVC ratio was not significantly associated with traffic exposure in either
      men or women. CONCLUSIONS: This is the largest published study of traffic
      exposure and pulmonary function in adults to date. These results add to growing
      evidence that chronic exposure to traffic related air pollution may adversely
      affect respiratory health.

PMID- 17442706
TI  - Alterations in upper airway cross-sectional area in response to lower body
      positive pressure in healthy subjects.
AB  - BACKGROUND: Fluid accumulation in the neck during recumbency might narrow the
      upper airway (UA) and thereby contribute to its collapse in patients with
      obstructive sleep apnoea (OSA). It is hypothesised that acute fluid shifts from
      the legs to the upper body in healthy subjects would increase neck circumference
      and reduce the cross-sectional area of the UA (UA-XSA). METHODS: In 27 healthy
      non-obese subjects of mean (SE) age 39 (3) years and body mass index 23.2 (0.6)
      kg/m2 studied while supine, leg fluid volume was measured using bioelectrical
      impedance, neck circumference using a mercury strain gauge and mean UA-XSA
      between the velum and the glottis using acoustic pharyngometry at end expiration.
      Measurements were made at baseline after which subjects were randomly assigned to
      a 5 min time control period or to a 5 min application of lower body positive
      pressure (LBPP) at 40 mm Hg by anti-shock trousers, separated by a 15 min washout
      period. Subjects then crossed over to the opposite arm of the study. RESULTS:
      Compared with control, application of LBPP significantly reduced leg fluid volume
      (p<0.001) and increased neck circumference (p<0.001), both at 1 min and 5 min,
      and reduced UA-XSA after both 1 min (-0.15 cm2; 95% CI -0.23 to -0.09, p<0.001)
      and 5 min (-0.20 cm2; 95% CI -0.33 to -0.09, p<0.001). CONCLUSION: In healthy
      subjects, displacement of fluid from the legs by LBPP causes distension of the
      neck and narrowing of the UA lumen. Fluid displacement from the lower to the
      upper body while recumbent may contribute to pharyngeal narrowing and obstruction
      to airflow in patients with OSA. This may have particular pathological
      significance in oedematous states such as heart and renal failure.

PMID- 17442707
TI  - Molecular and biochemical characterization of galectin from amphioxus: primitive
      galectin of chordates participated in the infection processes.
AB  - A novel F4-carbohydrate recognition domain (CRD)-linker-F3-CRD-type bi-CRD
      Branchiostoma belcheri tsingtauense galectin (BbtGal)-L together with its
      alternatively spliced mono-CRD isoform BbtGal-S from amphioxus intestine was
      encoded by a 9488-bp unique gene with eight exons and seven introns. The
      recombinant proteins of BbtGal were found to have beta-galactoside-binding
      activity, indicating that BbtGal was a member of the galectin family.
      Phylogenetic analysis of this gene along with its splicing form and genome
      structure suggested that the BbtGal gene was the primitive form of the chordate
      galectin family. Real-time polymerase chain reaction analyses (PCR) indicated
      that BbtGal mRNA was expressed during all stages of embryonic development. In
      terms of tissue distribution, BbtGal-L mRNA was mainly expressed in the immunity
      related organs, such as hepatic diverticulum, intestine, and gill, but BbtGal-S
      was ubiquitously expressed in all tissues. The expression of BbtGal-L mRNA was
      elevated after acute challenge with various microorganisms, but BbtGal-L only
      bound to specific bacteria. The immune function of BbtGal was consistent with its
      localization both outside and inside the cell. Our study on amphioxus galectin
      may help further understanding of the evolution of chordate galectin in terms of
      host-pathogen interaction in the immune system.

PMID- 17442708
TI  - Perlecan--a multifunctional extracellular proteoglycan scaffold.
AB  - Perlecan is a large multidomain heparan sulfate proteoglycan of the extracellular
      matrix. Expression of this proteoglycan changes dynamically during embryo
      implantation and placentation. Perlecan is expressed by various cells of the
      embryo including trophectoderm and trophoblast as well as the maternal
      compartment, including basal lamina underlying uterine epithelia and endothelia
      and, most dynamically, in developing decidua. Perlecan supports various
      biological functions, including cell adhesion, growth factor binding, and
      modulation of apoptosis. Moreover, studies in other systems demonstrate that
      perlecan expression and activity can be controlled at many levels, including
      transcription, alternative splicing, and extracellular proteolysis. This review
      will discuss changes in perlecan expression that occur during embryo implantation
      and placentation. Furthermore, we propose a model in which perlecan represents an
      extracellular scaffold protein that supports complex, distinct functions in its
      full-length form or smaller forms generated by alternative mRNA splicing,
      extracellular proteolysis, or glycosidase action.

PMID- 17442709
TI  - Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection causes apoptosis of
      infected CD4 T cells as well as uninfected (bystander) CD4 and CD8 T cells. It
      remains unknown what signals cause infected cells to die. We demonstrate that HIV
      1 protease specifically cleaves procaspase 8 to create a novel fragment termed
      casp8p41, which independently induces apoptosis. casp8p41 is specific to HIV-1
      protease-induced death but not other caspase 8-dependent death stimuli. In HIV-1
      infected patients, casp8p41 is detected only in CD4(+) T cells, predominantly in
      the CD27(+) memory subset, its presence increases with increasing viral load, and
      it colocalizes with both infected and apoptotic cells. These data indicate that
      casp8p41 independently induces apoptosis and is a specific product of HIV-1
      protease which may contribute to death of HIV-1-infected cells.

PMID- 17442710
TI  - Effects of viral strain, transgene position, and target cell type on replication
      kinetics, genomic stability, and transgene expression of replication-competent
      murine leukemia virus-based vectors.
AB  - The limited efficiency of in vivo gene transfer by replication-deficient
      retroviral vectors remains an obstacle to achieving effective gene therapy for
      solid tumors. One approach to circumvent this problem is the use of replication
      competent retroviral vectors. However, the application of such vectors is at a
      comparatively early stage and the effects which virus strain, transgene cassette
      position, and target cell can exert on vector spread kinetics, genomic stability,
      and transgene expression levels remain to be fully elucidated. Thus, in this
      study a panel of vectors allowing the investigation of different design features
      on an otherwise genetically identical background were analyzed with respect to
      these readout parameters in cultures of both murine and human cells and in
      preformed tumors in nude mice. The obtained data revealed that (i) Moloney murine
      leukemia virus (Mo-MLV)-based vectors spread with faster kinetics, drive higher
      levels of transgene expression, and are more stable than equivalent Akv-MLV-based
      vectors; (ii) vectors containing the transgene cassette directly downstream of
      the envelope gene are genomically more stable than those containing it within the
      3'-long terminal repeat U3 region; and (iii) the genomic stability of both
      strains seems to be cell line dependent.

PMID- 17442711
TI  - Activated CD34-derived Langerhans cells mediate transinfection with human
      immunodeficiency virus.
AB  - Langerhans cells (LCs) are a subset of dendritic cells (DCs) that reside within
      epidermal and mucosal tissue. Because of their location, LCs are potentially the
      first cells to encounter human immunodeficiency virus (HIV) during sexual
      transmission. We report that LCs purified from CD34(+)-derived DCs can facilitate
      the transinfection of target cells but only after activation. Virions were
      observed in an intracellular compartment that contains several tetraspanins, in
      addition to the unique LC markers langerin and CD1a. This reveals that the
      trafficking of HIV within LCs is reminiscent of that which occurs in mature
      monocyte-derived DCs and that it varies with the activation state of the cell.
      The observation that activated LCs can mediate transinfection suggests a
      potential role for these cells in the known increase in HIV transmission
      associated with sexually transmitted infections that would cause inflammation of
      the genital lining.

PMID- 17442712
TI  - Microtubule-mediated and microtubule-independent transport of adenovirus type 5
      in HEK293 cells.
AB  - Adenovirus serotypes 2 and 5 are taken into cells by receptor-mediated
      endocytosis, and following release from endosomes, destabilized virions travel
      along microtubules to accumulate around the nucleus. The entry process culminates
      in delivery of the viral genome through nuclear pores. This model is based on
      studies with conventional cell lines, such as HeLa and HEp-2, but in HEK293
      cells, which are routinely used in this laboratory because they are permissive
      for replication of multiple adenovirus serotypes, a different trafficking pattern
      has been observed. Nuclei of 293 cells have an irregular shape, with an indented
      region, and virions directly labeled with carboxyfluorescein accumulate in a
      cluster within that indented region. The clusters, which form in close proximity
      to the microtubule organizing center (MTOC) and to the Golgi apparatus, are
      remarkably stable; a fluorescent signal can be seen in the MTOC region up to 16 h
      postinfection. Furthermore, if cells are infected and then undergo mitosis after
      the cluster is formed, the signal is found at each spindle pole. Despite the
      sequestration of virions near the MTOC, 293 cells are no less sensitive than
      other cells to productive infection with adenovirus. Even though cluster
      formation depends on intact microtubules, infectivity is not compromised by
      disruption of microtubules with either nocodazole or colchicine, as determined by
      expression of an enhanced green fluorescent protein reporter gene inserted in the
      viral genome. These results indicate that virion clusters do not represent the
      infectious pathway and suggest an alternative route to the nucleus that does not
      depend on nocodazole-sensitive microtubules.

PMID- 17442713
TI  - Viral translation is coupled to transcription in Sindbis virus-infected cells.
AB  - During the late phase of Sindbis virus infection, the viral subgenomic mRNA is
      translated efficiently in BHK cells, whereas host protein synthesis is inhibited.
      However, transfection of in vitro-generated Sindbis virus subgenomic mRNA leads
      to efficient translation in uninfected BHK cells, whereas it is a poor substrate
      in infected cells. Therefore, the structure of the subgenomic mRNA itself is not
      sufficient to confer its translatability in infected cells. In this regard,
      translation of the subgenomic mRNA requires synthesis from the viral
      transcription machinery. The lack of translation of transfected viral mRNAs in
      infected cells is not due to their degradation nor is it a consequence of
      competition between viral transcripts and transfected mRNAs, because a replicon
      that cannot produce subgenomic mRNA also interferes with exogenous mRNA
      translation. Interestingly, subgenomic mRNA is translated more efficiently when
      it is transfected into uninfected cells than when it is transcribed from a
      transfected replicon. Finally, a similar behavior was observed for other RNA
      viruses, such as vesicular stomatitis virus and encephalomyocarditis virus. These
      findings support the notion that translation is coupled to transcription in cells
      infected with different animal viruses.

PMID- 17442714
TI  - Hepatitis B virus translocates across a trophoblastic barrier.
AB  - Mother-infant transmission of hepatitis B virus (HBV) accounts for up to 30% of
      worldwide chronic infections. The mechanism and high-risk period of HBV
      transmission from mother to infant are unknown. Although largely prevented by
      neonatal vaccination, significant transmission continues to occur in high-risk
      populations. It is unclear whether HBV can traverse an intact epithelial barrier
      to infect a new host. Transplacental transmission of a number of viruses relies
      on transcytotic pathways across placental cells. We wished to determine whether
      infectious HBV can traverse a polarized trophoblast monolayer. We used a human
      placenta-derived cell line, BeWo, cultured on membranes as polarized monolayers,
      to model the maternal-fetal barrier. We assessed the effects of placental
      maturity and maternal immunoglobulin on viral transport. Intracellular viral
      trafficking pathways were investigated by confocal microscopy. Free HBV (and
      infectious duck hepatitis B virus) transcytosed across trophoblastic cells at a
      rate of 5% in 30 min. Viral transport occurred in microtubule-dependent endosomal
      vesicles. Additionally, confocal microscopy showed that the internalized virus
      traverses a monensin-sensitive endosomal compartment. Differentiation of the
      cytotrophoblasts to syncytiotrophoblasts resulted in a 25% reduction in viral
      transcytosis, suggesting that placental maturity may protect the fetus. Virus
      translocation was also reduced in the presence of HBV immunoglobulin. We show for
      the first time that transcytosis of infectious hepadnavirus can occur across a
      trophoblastic barrier early in gestation, with the risk of transmission being
      reduced by placental maturity and specific maternal antibody. This study suggests
      a mechanism by which mother-infant transmission may occur.

PMID- 17442715
TI  - Kaposi's sarcoma-associated herpesvirus infection promotes invasion of primary
      human umbilical vein endothelial cells by inducing matrix metalloproteinases.
AB  - Matrix metalloproteinases (MMPs) play important roles in cancer invasion,
      angiogenesis, and inflammatory infiltration. Kaposi's sarcoma is a highly
      disseminated angiogenic tumor of proliferative endothelial cells linked to
      infection by Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we
      showed that KSHV infection increased the invasiveness of primary human umbilical
      vein endothelial cells (HUVEC) in a Matrigel-based cell invasion assay. KSHV
      induced cell invasion was abolished by an inhibitor of MMPs, BB-94, and occurred
      in both autocrine- and paracrine-dependent fashions. Analysis by zymography and
      Western blotting showed that KSHV-infected HUVEC cultures had increased secretion
      of MMP-1, -2, and -9. KSHV increased the secretion of MMP-2 within 1 h following
      infection without upregulating its mRNA expression level. In contrast, the
      secretion of MMP-1 and -9 was not increased until 6 h after KSHV infection and
      was correlated with the upregulation of their mRNA expression levels. Promoter
      analysis by reporter assays and electrophoretic mobility shift assays identified
      an AP-1 cis-element as the dominant KSHV-responsive site in the MMP-1 promoter.
      Together, these results suggest that KSHV infection modulates the production of
      multiple MMPs to increase cell invasiveness and thus contributes to the
      pathogenesis of KSHV-induced malignancies.

PMID- 17442716
TI  - The p110alpha isoform of phosphatidylinositol 3-kinase is essential for
      polyomavirus middle T antigen-mediated transformation.
AB  - Middle T antigen (MT) of polyomavirus is known to play an important role in virus
      mediated cellular transformation. While MT has been extensively examined in
      spontaneously immortalized rodent fibroblasts, its interactions with cells of
      other types and species are less well understood. We have undertaken a cross
      species and cross-cell-type comparison of MT-induced transformation in cells with
      genetically defined backgrounds. We tested the transforming abilities of a panel
      of MT mutants, Y250F, Y315F, and Y322F, that are selectively mutated in the
      binding sites for the principal effectors of MT--Src homology 2 domain-containing
      transforming protein, phosphatidylinositol 3-kinase (PI3K), and phospholipase C
      gamma, respectively--in fibroblasts and epithelial cells of murine or human
      origin. We found that the Y315F mutation disabled the ability of MT to induce
      transformation in all cell types and species tested. While Y315F also failed to
      activate the PI3K pathway in these cells, genetic evidence has indicated Y315 may
      make other contributions to transformation. To confirm the role of PI3K, the
      PIK3CA gene, encoding p110alpha, the prime effector of PI3K signaling downstream
      from activated growth factor receptors, was genetically ablated. This abolished
      the transforming activity of MT, demonstrating the essential role for this PI3K
      isoform in MT-mediated transformation. The Y250F mutant was able to transform the
      human, but not the murine, cells that were examined. Interestingly, this mutant
      fully activates the PI3K pathway in human cells but activated PI3K signaling
      poorly in the murine cells used in the study. This again points to the importance
      of PI3K activation for transformation and suggests that the mechanism by which MT
      activates the PI3K pathway differs in different species.

PMID- 17442717
TI  - Coxsackievirus B3 proteins directionally complement each other to downregulate
      surface major histocompatibility complex class I.
AB  - Picornaviruses carry a small number of proteins with diverse functions that
      subvert and exploit the host cell. We have previously shown that three
      coxsackievirus B3 (CVB3) proteins (2B, 2BC, and 3A) target the Golgi complex and
      inhibit protein transit. Here we investigate these effects in more detail and
      evaluate the distribution of major histocompatibility complex (MHC) class I
      molecules, which are critical mediators of the CD8(+) T-cell response. We report
      that concomitant with viral protein synthesis, MHC class I surface expression is
      rapidly downregulated during infection. However, this phenomenon may not result
      solely from inhibition of anterograde trafficking; we propose a new mechanism
      whereby the CVB3 2B and 2BC proteins upregulate the internalization of MHC class
      I (and possibly other surface proteins), perhaps by focusing of endocytic
      vesicles at the Golgi complex. Thus, our findings indicate that CVB3 carries at
      least three nonstructural proteins that directionally complement one another; 3A
      disrupts the Golgi complex to inhibit anterograde transport, while 2B and/or 2BC
      upregulates endocytosis, rapidly removing proteins from the cell surface. Taken
      together, these effects may render CVB3-infected cells invisible to CD8(+) T
      cells and untouchable by many antiviral effector molecules. This has important
      implications for immune evasion by CVB3.

PMID- 17442718
TI  - Ty3 capsid mutations reveal early and late functions of the amino-terminal
      domain.
AB  - The Ty3 retrotransposon assembles into 50-nm virus-like particles that occur in
      large intracellular clusters in the case of wild-type (wt) Ty3. Within these
      particles, maturation of the Gag3 and Gag3-Pol3 polyproteins by Ty3 protease
      produces the structural proteins capsid (CA), spacer, and nucleocapsid. Secondary
      and tertiary structure predictions showed that, like retroviral CA, Ty3 CA
      contains a large amount of helical structure arranged in amino-terminal and
      carboxyl-terminal bundles. Twenty-six mutants in which alanines were substituted
      for native residues were used to study CA subdomain functions. Transposition was
      measured, and particle morphogenesis and localization were characterized by
      analysis of protein processing, cDNA production, genomic RNA protection, and
      sedimentation and by fluorescence and electron microscopy. These measures defined
      five groups of mutants. Proteins from each group could be sedimented in a large
      complex. Mutations in the amino-terminal domain reduced the formation of
      fluorescent Ty3 protein foci. In at least one major homology region mutant, Ty3
      protein concentrated in foci but no wt clusters of particles were observed. One
      mutation in the carboxyl-terminal domain shifted assembly from spherical
      particles to long filaments. Two mutants formed foci separate from P bodies, the
      proposed sites of assembly, and formed defective particles. P-body association
      was therefore found to be not necessary for assembly but correlated with the
      production of functional particles. One mutation in the amino terminus blocked
      transposition after cDNA synthesis. Our data suggest that Ty3 proteins are
      concentrated first, assembly associated with P bodies occurs, and particle
      morphogenesis concludes with a post-reverse transcription, CA-dependent step.
      Particle formation was generally resistant to localized substitutions, possibly
      indicating that multiple domains are involved.

PMID- 17442719
TI  - Multiple anti-interferon actions of the influenza A virus NS1 protein.
AB  - The replication and pathogenicity of influenza A virus (FLUAV) are controlled in
      part by the alpha/beta interferon (IFN-alpha/beta) system. This virus-host
      interplay is dependent on the production of IFN-alpha/beta and on the capacity of
      the viral nonstructural protein NS1 to counteract the IFN system. Two different
      mechanisms have been described for NS1, namely, blocking the activation of IFN
      regulatory factor 3 (IRF3) and blocking posttranscriptional processing of
      cellular mRNAs. Here we directly compare the abilities of NS1 gene products from
      three different human FLUAV (H1N1) strains to counteract the antiviral host
      response. We found that A/PR/8/34 NS1 has a strong capacity to inhibit IRF3 and
      activation of the IFN-beta promoter but is unable to suppress expression of other
      cellular genes. In contrast, the NS1 proteins of A/Tx/36/91 and of A/BM/1/18, the
      virus that caused the Spanish influenza pandemic, caused suppression of
      additional cellular gene expression. Thus, these NS1 proteins prevented the
      establishment of an IFN-induced antiviral state, allowing virus replication even
      in the presence of IFN. Interestingly, the block in gene expression was dependent
      on a newly described NS1 domain that is important for interaction with the
      cleavage and polyadenylation specificity factor (CPSF) component of the cellular
      pre-mRNA processing machinery but is not functional in A/PR/8/34 NS1. We
      identified the Phe-103 and Met-106 residues in NS1 as being critical for CPSF
      binding, together with the previously described C-terminal binding domain. Our
      results demonstrate the capacity of FLUAV NS1 to suppress the antiviral host
      defense at multiple levels and the existence of strain-specific differences that
      may modulate virus pathogenicity.

PMID- 17442720
TI  - Infectious bursal disease virus capsid assembly and maturation by structural
      rearrangements of a transient molecular switch.
AB  - Infectious bursal disease virus (IBDV), a double-stranded RNA (dsRNA) virus
      belonging to the Birnaviridae family, is an economically important avian
      pathogen. The IBDV capsid is based on a single-shelled T=13 lattice, and the only
      structural subunits are VP2 trimers. During capsid assembly, VP2 is synthesized
      as a protein precursor, called pVP2, whose 71-residue C-terminal end is
      proteolytically processed. The conformational flexibility of pVP2 is due to an
      amphipathic alpha-helix located at its C-terminal end. VP3, the other IBDV major
      structural protein that accomplishes numerous roles during the viral cycle, acts
      as a scaffolding protein required for assembly control. Here we address the
      molecular mechanism that defines the multimeric state of the capsid protein as
      hexamers or pentamers. We used a combination of three-dimensional cryo-electron
      microscopy maps at or close to subnanometer resolution with atomic models. Our
      studies suggest that the key polypeptide element, the C-terminal amphipathic
      alpha-helix, which acts as a transient conformational switch, is bound to the
      flexible VP2 C-terminal end. In addition, capsid protein oligomerization is also
      controlled by the progressive trimming of its C-terminal domain. The coordination
      of these molecular events correlates viral capsid assembly with different
      conformations of the amphipathic alpha-helix in the precursor capsid, as a five
      alpha-helix bundle at the pentamers or an open star-like conformation at the
      hexamers. These results, reminiscent of the assembly pathway of positive single
      stranded RNA viruses, such as nodavirus and tetravirus, add new insights into the
      evolutionary relationships of dsRNA viruses.

PMID- 17442721
TI  - Molecular behaviors of "CH1641-like" sheep scrapie isolates in ovine transgenic
      mice (TgOvPrP4).
AB  - Molecular analyses of the protease-resistant prion protein (PrP(res)) from a few
      natural scrapie isolates showed by Western blotting some partial similarities
      with those observed in experimental ovine bovine spongiform encephalopathy (BSE).
      They showed a low apparent molecular mass of unglycosylated PrP(res), although
      diglycosylated PrP(res) was less abundant than in ovine BSE. The prototype of
      such cases is the CH1641 experimental scrapie isolate. We analyzed PrP(res)
      molecular features from three French natural "CH1641-like" isolates, in
      comparison with CH1641 and BSE, after transmission of the disease in ovine
      transgenic mice (TgOvPrP4). One of these isolates (TR316211) behaved like the
      CH1641 isolate, with PrP(res) features in mice similar to those in the sheep
      brain. From two other isolates (O100 and O104), two distinct PrP(res) phenotypes
      were identified in mouse brains, with either high (h-type) or low (l-type)
      apparent molecular masses of unglycosylated PrP(res), the latter being similar to
      that observed with CH1641, TR316211, or BSE. Both phenotypes could be found in
      variable proportions in the brains of the individual mice. In contrast with BSE,
      l-type PrP(res) from "CH1641-like" isolates showed lower levels of diglycosylated
      PrP(res). From one of these cases (O104), a second passage in mice was performed
      for two mice with distinct PrP(res) profiles. This showed a partial selection of
      the l-type phenotype in mice infected with a mouse brain with predominant l-type
      PrP(res), and it was accompanied by a significant increase in the proportions of
      the diglycosylated band. These results are discussed in relation to the diversity
      of scrapie and BSE strains.

PMID- 17442722
TI  - Murine gammaherpesvirus 68 contains two functional lytic origins of replication.
AB  - A 1.25-kbp DNA fragment from the right side of the genome containing the lytic
      origin of replication (oriLyt) of murine gammaherpesvirus 68 (MHV-68) has been
      identified by a plasmid replication assay. Here we show that a mutant MHV-68 with
      a deletion of an essential part of this oriLyt, generated by using an MHV-68
      bacterial artificial chromosome, was only slightly attenuated and still able to
      replicate but that a mutant containing an additional deletion on the left side of
      the genome was replication deficient. The newly identified region was sufficient
      to support plasmid replication, thus providing evidence for a second oriLyt.

PMID- 17442723
TI  - Prion protein alleles showing a protective effect on the susceptibility of sheep
      to scrapie and bovine spongiform encephalopathy.
AB  - The susceptibility of sheep to classical scrapie and bovine spongiform
      encephalopathy (BSE) is mainly influenced by prion protein (PrP) polymorphisms
      A136V, R154H, and Q171R, with the ARR allele associated with significantly
      decreased susceptibility. Here we report the protective effect of the amino acid
      substitution M137T, I142K, or N176K on the ARQ allele in sheep experimentally
      challenged with either scrapie or BSE. Such observations suggest the existence of
      additional PrP alleles that significantly decrease the susceptibility of sheep to
      transmissible spongiform encephalopathies, which may have important implications
      for disease eradication strategies.

PMID- 17442724
TI  - Altered interaction of the matrix protein with the cytoplasmic tail of
      hemagglutinin modulates measles virus growth by affecting virus assembly and cell
      cell fusion.
AB  - Clinical isolates of measles virus (MV) use signaling lymphocyte activation
      molecule (SLAM) as a cellular receptor, whereas vaccine and laboratory strains
      may utilize the ubiquitously expressed CD46 as an additional receptor. MVs also
      infect, albeit inefficiently, SLAM(-) cells, via a SLAM- and CD46-independent
      pathway. Our previous study with recombinant chimeric viruses revealed that not
      only the receptor-binding hemagglutinin (H) but also the matrix (M) protein of
      the Edmonston vaccine strain can confer on an MV clinical isolate the ability to
      grow well in SLAM(-) Vero cells. Two substitutions (P64S and E89K) in the M
      protein which are present in many vaccine strains were found to be responsible
      for the efficient growth of recombinant virus in Vero cells. Here we show that
      the P64S and E89K substitutions allow a strong interaction of the M protein with
      the cytoplasmic tail of the H protein, thereby enhancing the assembly of
      infectious particles in Vero cells. These substitutions, however, are not
      necessarily advantageous for MVs, as they inhibit SLAM-dependent cell-cell
      fusion, thus reducing virus growth in SLAM(+) B-lymphoblastoid B95a cells. When
      the cytoplasmic tail of the H protein is deleted, a virus with an M protein
      possessing the P64S and E89K substitutions no longer grows well in Vero cells yet
      causes cell-cell fusion and replicates efficiently in B95a cells. These results
      reveal a novel mechanism of adaptation and attenuation of MV in which the altered
      interaction of the M protein with the cytoplasmic tail of the H protein modulates
      MV growth in different cell types.

PMID- 17442725
TI  - "Subclinical" gentamicin nephrotoxicity: a potential risk factor for exaggerated
      endotoxin-driven TNF-alpha production.
AB  - This study sought to determine whether gentamicin, a mainstay in treating Gram
      negative sepsis, alters endotoxin (lipopolysaccharide; LPS)-driven TNF-alpha
      increases. CD-1 mice received 1 day of gentamicin treatment. Either 0, 24, or 72
      h later, gentamicin-treated and control mice were injected with LPS. Renal
      cortical and plasma TNF-alpha, as well as MCP-1, protein levels were measured 2
      or 24 h post-LPS injection. Renal cortical mRNAs for TNF-alpha, MCP-1, IL-10, and
      inducible nitric oxide synthase (iNOS) were also determined. Finally,
      gentamicin's potential impact(s) on TNF-alpha/MCP-1 mRNA levels in nontraditional
      "target" organs (liver, spleen) was assessed. Gentamicin, when administered
      alone, slightly increased renal cortical TNF-alpha and MCP-1 mRNAs, but without
      changing plasma or renal TNF-alpha/MCP-1 protein levels. The gentamicin protocol
      induced no overt renal damage (assessed by blood urea nitrogen, creatinine, and
      histology). Nevertheless, gentamicin augmented LPS responsiveness, as manifested,
      in part, by a doubling of LPS-induced plasma TNF-alpha increases (vs. LPS
      injection alone). Plasma and renal cortical MCP-1 protein levels were also
      selectively enhanced. Gentamicin augmented LPS-driven renal mRNA increases (TNF
      alpha, MCP-1, IL-10, iNOS). However, this was not an entirely renal-specific
      response, since gentamicin also enhanced basal and LPS-stimulated hepatic TNF
      alpha mRNA levels. Subclinical gentamicin toxicity can potentiate LPS-driven TNF
      alpha increases. Alterations in multiple proinflammatory (TNF-alpha; MCP-1; iNOS)
      and anti-inflammatory (IL-10) genes in the kidney, and possibly in extrarenal
      organs, may be involved. Thus gentamicin's activity in Gram-negative sepsis may
      extend beyond its traditional antimicrobial effect.

PMID- 17442726
TI  - Molecular identification and functional characterization of rabbit MATE1 and
      MATE2-K.
AB  - An electroneutral organic cation (OC)/proton exchanger in the apical membrane of
      proximal tubules mediates the final step of renal OC excretion. Two members of
      the multidrug and toxin extrusion family, MATE1 and MATE2-K, were recently
      identified in human and rodent kidney and proposed to be the molecular basis of
      renal OC/H(+) exchange. To take advantage of the comparative value of the large
      database on the kinetic and selectivity characteristics of OC/H(+) exchange that
      exists for rabbit kidney, we cloned rbMATE1 and rbMATE2-K. The rabbit homologs
      have 75% (MATE1) and 74% (MATE2-K) amino acid identity to their human
      counterparts (and 51% identity with each other). rbMATE1 and rbMATE2-K exhibited
      H(+) gradient-dependent uptake and efflux of tetraethylammonium (TEA) when
      expressed in Chinese hamster ovary cells. Both transporters displayed similar
      affinities for selected compounds [IC(50) values within 2-fold for TEA, 1-methyl
      4-phenylpyridinium, and quinidine] and very different affinities for others
      (IC(50) values differing by 8- to 80-fold for choline and cimetidine,
      respectively). These results indicate that rbMATE1 and rbMATE2-K are
      multispecific OC/H(+) exchangers with similar, but distinct, functional
      characteristics. Overall, the selectivity of MATE1 and MATE2-K correlated closely
      with that observed in rabbit renal brush-border membrane vesicles.

PMID- 17442727
TI  - Angiotensin AT1-receptor inhibition exacerbates renal injury resulting from
      partial unilateral ureteral obstruction in the neonatal rat.
AB  - The renin-angiotensin system is activated in the developing kidney and is
      necessary for normal renal development, but is further activated by unilateral
      ureteral obstruction (UUO). During nephrogenesis, there is a switch from a
      preponderance of angiotensin AT(2) to AT(1) receptors in the rat. We examined the
      renal cellular response to angiotensin II receptor inhibition in the neonatal rat
      subjected to partial UUO under anesthesia within 48 h of birth. Group I ("early")
      received saline vehicle, losartan (AT(1) inhibitor), or PD-123319 (AT(2)
      inhibitor) during the completion of nephrogenesis in the first 10 days of life.
      Group II ("late") received each of the three treatments throughout the subsequent
      10 days of life. Kidneys were harvested at 21 days, and the distribution of
      renin, apoptosis, macrophages, alpha-smooth muscle actin, and collagen was
      determined. Losartan and PD-123319 each increased vascular renin distribution in
      both kidneys. Partial UUO reduced growth and increased apoptosis, macrophages,
      alpha-smooth muscle actin, and collagen in the obstructed kidney. Early losartan
      treatment further increased alpha-smooth muscle actin and collagen in the
      obstructed kidney and induced apoptosis, macrophages, and collagen in the
      contralateral kidney. Late losartan treatment had no effect on any of the
      parameters in either kidney, and PD-123319 had no effect on either kidney. We
      conclude that selective inhibition of AT(1) receptors during nephrogenesis (but
      not during subsequent renal maturation) exacerbates injury to the obstructed
      kidney and also injures the contralateral kidney. These results suggest that
      angiotensin II receptor blockers should be avoided in the developing
      hydronephrotic kidney.

PMID- 17442728
TI  - Sex and age differences of renal function in rats with reduced ANG II activity
      during the nephrogenic period.
AB  - This study was designed to test the hypothesis that blockade of angiotensin II
      effects during renal development accelerates the aging-related changes in renal
      hemodynamics and proteinuria, and that these changes are sex dependent. It has
      also been examined whether the deterioration of urinary concentrating ability
      elicited by angiotensin II blockade is sex and/or aging dependent. Newborn
      Sprague-Dawley rats were treated with vehicle or an AT(1) angiotensin II receptor
      antagonist (ARA) during the first 14 postnatal days. Blood pressure, glomerular
      filtration rate, proteinuria, and urinary concentrating ability in response to
      dehydration were examined in conscious rats at 3 and 11 mo of age. ARA treatment
      elicited a similar increment in blood pressure in males and females that was
      greater (P < 0.05) at 11 than at 3 mo of age. Glomerular filtration rate only
      decreased (P < 0.05) in 11-mo-old male ARA-treated rats (0.59 +/- 0.07 vs. 0.80
      +/- 0.07 ml.min(-1).g(-1) in control group). At 3 mo of age, proteinuria
      increased in male (107%) but not in female ARA-treated rats. However, at 11 mo of
      age, proteinuria increased in both sexes, but the increment was greater (P <
      0.05) in male (244%) than in female (138%) ARA-treated rats. Renal ability to
      concentrate urine in response to prolonged water dehydration was only reduced in
      ARA-treated males. The reduction of urinary concentrating ability was accentuated
      by aging. Therefore, we conclude that blockade of angiotensin II effects during
      renal development elicits an important deterioration of cortical and medullary
      function that is sex and aging dependent.

PMID- 17442729
TI  - Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates
      abnormal renal function and hypertension in obese rats.
AB  - Since epoxyeicosatrienoic acids (EETs) affect sodium reabsorption in renal
      tubules and dilate the renal vasculature, we have examined their effects on renal
      hemodynamics and sodium balance in male rats fed a high-fat (HF) diet by
      fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-alpha)
      agonist and an inducer of cytochrome P-450 (CYP) epoxygenases; by N
      methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH), a selective EET
      biosynthesis inhibitor; and by 12-(3-adamantane-1-yl-ureido)dodecanoic acid
      (AUDA), a selective inhibitor of soluble epoxide hydrolase. In rats treated with
      fenofibrate (30 mg.kg(-1).day(-1) ig) or AUDA (50 mg/l in drinking water) for 2
      wk, mean arterial pressure, renal vascular resistance, and glomerular filtration
      rate were lower but renal blood flow was higher than in vehicle-treated control
      rats. In addition, fenofibrate and AUDA decreased cumulative sodium balance in
      the HF rats. Treatment with MSPPOH (20 mg.kg(-1).day(-1) iv) + fenofibrate for 2
      wk reversed renal hemodynamics and sodium balance to the levels in control HF
      rats. Moreover, fenofibrate caused a threefold increase in renal cortical CYP
      epoxygenase activity, whereas the fenofibrate-induced elevation of this activity
      was attenuated by MSPPOH. Western blot analysis showed that fenofibrate induced
      the expression of CYP epoxygenases in renal cortex and microvessels and that the
      induction effect of fenofibrate was blocked by MSPPOH. These results demonstrate
      that the fenofibrate-induced increase of CYP epoxygenase expression and the AUDA
      induced stabilization of EET production in the kidneys cause renal vascular
      dilation and reduce sodium retention, contributing to the improvement of abnormal
      renal hemodynamics and hypertension in HF rats.

PMID- 17442730
TI  - The prokineticin receptor-1 (GPR73) promotes cardiomyocyte survival and
      angiogenesis.
AB  - Prokineticins are potent angiogenic factors that bind to two G protein-coupled
      receptors to initiate their biological effects. We hypothesize that prokineticin
      receptor-1 (PKR1/GPR73) signaling may contribute to cardiomyocyte survival or
      repair in myocardial infarction. Since we showed that prokineticin-2 and PKR1 are
      expressed in adult mouse heart and cardiac cells, we investigated the role of
      prokineticin-2 on capillary endothelial cell and cardiomyocyte function. In
      cultured cardiac endothelial cells, prokineticin-2 or overexpression of PKR1
      induces vessel-like formation without increasing VEGF levels. In cardiomyocytes
      and H9c2 cells, prokineticin-2 or overexpressing PKR1 activates Akt to protect
      cardiomyocytes against oxidative stress. The survival and angiogenesis promoting
      effects of prokineticin-2 in cardiac cells were completely reversed by siRNA
      PKR1, indicating PKR1 involvement. We thus, further investigated whether
      intramyocardial gene transfer of DNA encoding PKR1 may rescue the myocardium
      against myocardial infarction in mouse model. Transient PKR1 gene transfer after
      coronary ligation reduces mortality and preserves left ventricular function by
      promoting neovascularization and protecting cardiomyocytes without altering VEGF
      levels. In human end-stage failing heart samples, reduced PKR1 and prokineticin-2
      transcripts and protein levels implicate a more important role for prokineticin
      2/PKR1 signaling in heart. Our results suggest that PKR1 may represent a novel
      therapeutic target to limit myocardial injury following ischemic events.

PMID- 17442731
TI  - Contribution of E-NTPDase1 (CD39) to renal protection from ischemia-reperfusion
      injury.
AB  - Previous studies showed increased extracellular nucleotides during renal ischemia
      reperfusion. While nucleotides represent the main source for extracellular
      adenosine and adenosine signaling contributes to renal protection from ischemia,
      we hypothesized a role for ecto-nucleoside-triphosphate-diphosphohydrolases (E
      NTPDases) in renal protection. We used a model of murine ischemia-reperfusion and
      in situ ischemic preconditioning (IP) via a hanging weight system for atraumatic
      renal artery occlusion. Initial studies with a nonspecific inhibitor of E
      NTPDases (POM-1) revealed inhibition of renal protection by IP. We next pursued
      transcriptional responses of E-NTPDases (E-NTPDase1-3, and 8) to renal IP, and
      found a robust and selective induction of E-NTPDase1/CD39 transcript and protein.
      Moreover, based on clearance studies, plasma electrolytes, and renal tubular
      histology, IP protection was abolished in gene-targeted mice for cd39 whereas
      increased renal adenosine content with IP was attenuated. Furthermore,
      administration of apyrase reconstituted renal protection by IP in cd39-/- mice.
      Finally, apyrase treatment of wild-type mice resulted in increased renal
      adenosine concentrations and a similar degree of renal protection from ischemia
      as IP treatment. Taken together, these data identify CD39-dependent nucleotide
      phosphohydrolysis in renal protection. Moreover, the present studies suggest
      apyrase treatment as a novel pharmacological approach to renal diseases
      precipitated by limited oxygen availability.

PMID- 17442732
TI  - Exaggerated apoptosis and NF-kappaB activation in pancreatic and tracheal cystic
      fibrosis cells.
AB  - The pathophysiologic mechanisms causing inflammation in cystic fibrosis (CF)
      remain obscure. The effects of proapoptotic agents on pancreatic and tracheal
      cell lines expressing wild-type CFTR (PANC-1 and NT-1, respectively) or the
      homozygous CFTRDeltaF508 mutation (CFPAC-1 and CFT-2, respectively) were
      assessed. An increased susceptibility to apoptosis was observed in CFPAC-1 and
      CFT-2 cells. Apoptosis was reduced by treatment with a pan-caspase inhibitor and
      by incubation at 27 degrees C, allowing recruitment of CFTR deltaF508 at the
      plasma membrane. Inhibition of CFTR function in wild-type cells induced an
      increase of apoptosis. Apoptosis in CFPAC-1, but not in CFT-2 cells, was
      associated with overexpression of the proinflammatory mediators interleukin-6 and
      interleukin-8. In CF cells, apoptosis was linked to NF-kappaB pathway activation.
      Conditioned medium from actinomycin D-treated CFPAC-1 cells produced an increase
      in apoptosis of wild-type cells, suggesting that proinflammatory mediators
      secreted by mutant cells promote apoptosis. This was confirmed through the
      induction of apoptosis in wild-type cells by exogenous interleukin-6 and
      interleukin-8. These results suggest that CFTR deltaF508 mutation, apoptosis, and
      activation of the NF-kappaB pathway contribute to the self-perpetuating
      inflammatory cycle, at least in pancreatic cells, and provide evidence that
      excessive apoptosis may account for the exaggerated proinflammatory response
      observed in CF patients.

PMID- 17442733
TI  - p53-dependent NDRG1 expression induces inhibition of intestinal epithelial cell
      proliferation but not apoptosis after polyamine depletion.
AB  - Normal intestinal mucosal growth requires polyamines that regulate expression of
      various genes involved in cell proliferation, growth arrest, and apoptosis. Our
      previous studies have shown that polyamine depletion stabilizes p53, resulting in
      inhibition of intestinal epithelial cell (IEC) proliferation, but the exact
      downstream targets of induced p53 are still unclear. The NDRG1 (N-myc
      downregulated gene-1) gene encodes a growth-related protein, and its
      transcription can be induced in response to stress. The current study tests the
      hypothesis that induced p53 inhibits IEC proliferation by upregulating NDRG1
      expression following polyamine depletion. Depletion of cellular polyamines by
      inhibiting ornithine decarboxylase (ODC) with alpha-difluoromethylornithine not
      only induced p53 but also increased NDRG1 transcription as indicated by induction
      of the NDRG1 promoter activity and increased levels of NDRG1 mRNA and protein,
      all of which were prevented by using specific p53 siRNA and in cells with a
      targeted deletion of p53. In contrast, increased levels of cellular polyamines by
      ectopic expression of the ODC gene decreased p53 and repressed expression of
      NDRG1. Consistently, polyamine depletion-induced activation of the NDRG1-promoter
      was decreased when p53-binding sites within the NDRG1 proximal promoter region
      were deleted. Ectopic expression of the wild-type NDRG1 gene inhibited DNA
      synthesis and decreased final cell numbers regardless of the presence or absence
      of endogenous p53, whereas silencing NDRG1 promoted cell growth. However,
      overexpression of NDRG1 failed to directly induce cell death and to alter
      susceptibility to apoptosis induced by tumor necrosis factor-alpha/cycloheximide.
      These results indicate that NDRG1 is one of the direct mediators of induced p53
      following polyamine depletion and that p53-dependent NDRG1 expression plays a
      critical role in the negative control of IEC proliferation.

PMID- 17442734
TI  - Normoxic stabilization of HIF-1alpha drives glycolytic metabolism and regulates
      aggrecan gene expression in nucleus pulposus cells of the rat intervertebral
      disk.
AB  - The nucleus pulposus is an aggrecan-rich, avascular tissue that permits the
      intervertebral disk to resist compressive loads. In the disk, nucleus pulposus
      cells express hypoxia-inducible factor (HIF)-1alpha, a transcription factor that
      responds to oxygen tension and regulates glycolysis. The goal of the present
      study was to examine the importance of HIF-1alpha in rat nucleus pulposus cells
      and to probe the function of this transcription factor in terms of regulating
      aggrecan gene expression. We found that HIF-1alpha protein levels and mRNA
      stability were similar at 20 and 2% O(2); there was a small, but significant
      increase in HIF-1alpha transactivation domain activity in hypoxia. With respect
      to HIF-1alpha target genes GAPDH, GLUT-1, and GLUT-3, mRNA and protein levels
      were independent of the oxygen tension. Other than a modest increase in 6
      phosphofructo-2-kinase/fructose-2,6-biphosphatase reporter activity, the oxemic
      state did not change GAPDH, GLUT-1, and GLUT-3 promoter activities. Treatment of
      cells with 2-deoxyglucose (2-DG), a glycolytic inhibitor, resulted in a
      significant suppression in ATP synthesis in normoxia, whereas treatment with
      mitochondrial inhibitors did not affect ATP production and cell viability.
      However, measurement of the rate of fatty acid oxidation indicated that these
      cells contained functioning mitochondria. Finally, we showed that when HIF-1alpha
      was suppressed, irrespective of the oxemic state, there was a partial loss of
      aggrecan expression and promoter activity. Moreover, when cells were treated with
      2-DG, there was inhibition in aggrecan promoter activity. Results of this study
      indicate that oxygen-independent stabilization of HIF-1alpha in nucleus pulposus
      cells is a metabolic adaptation that drives glycolysis and aggrecan expression.

PMID- 17442735
TI  - MKP-1 switches arginine metabolism from nitric oxide synthase to arginase
      following endotoxin challenge.
AB  - L-Arginine (L-arg) is metabolized to nitric oxide (NO) by inducible NO synthase
      (iNOS) or to urea and L-ornithine (L-orn) by arginase. NO is involved in the
      inflammatory response, whereas arginase is the first step in polyamine and
      proline synthesis necessary for tissue repair and wound healing. Mitogen
      activated protein kinases (MAPK) mediate LPS-induced iNOS expression, and MAPK
      phosphatase-1 (MKP-1) plays a crucial role in limiting MAPK signaling in
      macrophages. We hypothesized that MKP-1, by attenuating iNOS expression, acts as
      a switch changing L-arg metabolism from NO production to L-orn production after
      endotoxin administration. To test this hypothesis, we performed studies in
      RAW264.7 macrophages stably transfected with an MKP-1 expression vector in
      thioglyollate-elicited peritoneal macrophages harvested from wild-type and Mkp-1(
      /-) mice, as well as in vivo in wild-type and Mkp-1(-/-) mice. We found that
      overexpression of MKP-1 resulted in lower iNOS expression and NO production but
      greater urea production in response to LPS. Although deficiency of MKP-1 resulted
      in greater iNOS expression and NO production and lower urea production in
      response to LPS, neither the overexpression nor the deficiency of MKP-1 had any
      substantial effect on the expression of the arginases.

PMID- 17442736
TI  - Hypoxic upregulation of glucose transporters in BeWo choriocarcinoma cells is
      mediated by hypoxia-inducible factor-1.
AB  - Placental hypoxia has been implicated in pregnancy pathologies, including fetal
      growth restriction and preeclampsia; however, the mechanism by which the
      trophoblast cell responds to hypoxia has not been adequately explored. Glucose
      transport, a process crucial to fetoplacental growth, is upregulated by hypoxia
      in a number of cell types. We investigated the effects of hypoxia on the
      regulation of trophoblast glucose transporter (GLUT) expression and activity in
      BeWo choriocarcinoma cells, a trophoblast cell model, and human placental villous
      tissue explants. GLUT1 expression in BeWo cells was upregulated by the hypoxia
      inducing chemical agents desferroxamine and cobalt chloride. Reductions in oxygen
      tension resulted in dose-dependent increases in GLUT1 and GLUT3 expression.
      Exposure of cells to hypoxic conditions also resulted in an increase in
      transepithelial glucose transport. A role for hypoxia-inducible factor (HIF)-1
      was suggested by the increase in HIF-1alpha as a result of hypoxia and by the
      increase in GLUT1 expression following treatment of BeWo with MG-132, a
      proteasomal inhibitor that increases HIF-1 levels. The function of HIF-1 was
      confirmed in experiments where the hypoxic upregulation of GLUT1 and GLUT3 was
      inhibited by antisense HIF-1alpha. In contrast to BeWo cells, hypoxia produced
      minimal increases in GLUT1 expression in explants; however, treatment with MG-132
      did upregulate syncytial basal membrane GLUT1. Our results show that GLUTs are
      upregulated by hypoxia via a HIF-1-mediated pathway in trophoblast cells and
      suggest that the GLUT response to hypoxia in vivo will be determined not only by
      low oxygen tension but also by other factors that modulate HIF-1 levels.

PMID- 17442738
TI  - Why does post-transplant osteonecrosis develop?

PMID- 17442737
TI  - Differential effects of beta-arrestins on the internalization, desensitization
      and ERK1/2 activation downstream of protease activated receptor-2.
AB  - Beta-arrestins-1 and 2 are known to play important roles in desensitization of
      membrane receptors and facilitation of signal transduction pathways. It has been
      previously shown that beta-arrestins are required for signal termination,
      internalization, and ERK1/2 activation downstream of protease-activated-receptor
      2 (PAR-2), but it is unclear whether they are functionally redundant or mediate
      specific events. Here, we demonstrate that in mouse embryonic fibroblasts (MEFs)
      from beta-arrestin-1/2 knockout mice, G alpha q signaling by PAR-2, as measured
      by mobilization of intracellular Ca(2+), is prolonged. Only expression of beta
      arrestin-1 shortened the signal duration, whereas either beta-arrestin-1 or 2 was
      able to restore PKC-induced receptor desensitization. Beta-arrestin-1 also
      mediated early, while beta-arrestin-2 mediated delayed, receptor internalization
      and membrane-associated ERK1/2 activation. While beta-arrestin-1 colocalized with
      a lysosomal marker (LAMP-1), beta-arrestin-2 did not, suggesting a specific role
      for beta-arrestin-1 in lysosomal receptor degradation. Together, these data
      suggest distinct temporal and functional roles for beta-arrestins in PAR-2
      signaling, desensitization, and internalization.

PMID- 17442739
TI  - Focal segmental glomerulosclerosis is not a sufficient predictor of renal outcome
      in patients with membranous nephropathy.
AB  - BACKGROUND: The course of idiopathic membranous nephropathy (iMN) is variable in
      untreated patients. Accurate prediction of renal outcome would allow optimal
      treatment decisions. We demonstrated that urinary beta2-microglobulin (beta2M)
      predicted prognosis in iMN with high sensitivity and specificity. It has been
      suggested that focal segmental glomerulosclerosis (FSGS) is a discriminative
      parameter with independent prognostic value. METHODS: We selected patients with
      iMN biopsied between 1988 and 2002. Biopsies were analysed for the presence of
      FSGS, interstitial fibrosis and vascular lesions. Serum creatinine, creatinine
      clearance, proteinuria and blood pressure were recorded at baseline. Outcome
      variables included remission of proteinuria, renal death (RD) defined as serum
      creatinine >135 micromol/l or increase of serum creatinine of >50%, or end-stage
      renal disease (ESRD). In a subgroup of patients, urinary beta2-microglobulin
      (beta2M) was measured. RESULTS: We included 53 patients (33M, 20F). Mean age was
      51 years, serum creatinine 99 micromol/l, and proteinuria 7.0 g/10 mmol
      creatinine. FSGS was present in 22 patients. These patients were characterized by
      a higher serum creatinine at time of biopsy (P = 0.035), more severe interstitial
      fibrosis (P = 0.001) and higher stage of membranous nephropathy (P = 0.001).
      During follow-up 24 patients developed RD, almost equally distributed between
      patients with and without FSGS. Renal survival was numerically, but not
      significantly, lower in patients with FSGS. In Cox proportional hazard analysis,
      only serum creatinine at the time of biopsy was an independent predictor of RD or
      ESRD (P < 0.001). In patients with known urinary beta2M, there was no significant
      correlation with FSGS score (P = 0.174). CONCLUSION: FSGS is not an accurate
      prognostic marker in iMN. Histological scoring of FSGS is inferior to measurement
      of urinary proteins in predicting renal outcome in iMN.

PMID- 17442740
TI  - Accuracy of ultrasonic detection of renal scarring in different centres using
      DMSA as the gold standard.
AB  - BACKGROUND: There is an ongoing debate over the radiological investigations of
      children with urinary tract infections (UTIs) with some authorities suggesting
      that ultrasound scan (USS) alone is an accurate tool to diagnose renal
      parenchymal scarring post-pyelonephritis. All studies on this subject have been
      performed at paediatric teaching centres whereas most children with UTIs are
      managed by General Paediatricians in District General Hospitals (DGHs) in the
      United Kingdom. We wished to identify whether results of scans in DGHs differed
      from those in teaching centres. METHODS: We looked at all children with a
      clinical history of UTIs having a DMSA and USS over a one year period in two DGHs
      and one teaching centre. A total of 476 children's results were reviewed, 297
      from the DGHs and 179 from the teaching centre. RESULTS: The cohort had a total
      of 949 renal units. There were 79 scarred renal units (kidneys) on DMSA (8%) in
      72 patients (15%). Just 18 renal units were detected as being scarred on USS
      (22.8%). Nine of 32 scarred renal units in the teaching centre were detected
      compared with nine of 47 in the DGHs (P = 0.40). Thirty-nine (49%) of the scarred
      renal units were in patients >5-years old. Of these 12 (30.7%) were detected on
      USS, nine of 17 within the teaching centre compared with just three of 22 at the
      DGHs (P = 0.01). CONCLUSION: Overall only a small percentage of scars are
      detected on USS. In the over 5-year old group, where USS alone might be
      preferred, DGHs were significantly worse at detecting scarred kidneys. We
      conclude that if the detection of renal scars is a prime reason for imaging in
      children with UTIs, ultrasonography alone is inappropriate at any age and DMSA
      ought to be the primary investigation.

PMID- 17442741
TI  - Predicting adherence to immunosuppressant therapy: a prospective analysis of the
      theory of planned behaviour.
AB  - BACKGROUND: The objective of this study was to increase the ability to predict
      renal transplant patients (RTPs) who are most likely to be non-adherent to their
      immunosuppressant therapy (IST). METHODS: One hundred and fifty-eight RTPs
      completed questionnaires assessing Theory of Planned Behaviour (TPB) variables
      (attitudes, subjective norms and perceived behavioural control) relevant to
      intentions to adhere to their IST, with the addition of a general measure of past
      adherence to medical advice. In the full sample, intentions to adhere to IST was
      the outcome variable. In a subsample of 70 RTPs, the primary outcome was IST
      adherence. RESULTS: TPB variables (attitudes, beta = 0.32, P < 0.01; perceived
      behavioural control, beta = 0.37, P < 0.01; but not subjective norms, beta = 
      0.001, ns) explained 41% of the variance in intentions to adhere to IST (P <
      0.001). Past behaviour predicted perceived behavioural control (beta = 0.67, P <
      0.001). Subsample analyses explained 33% (P < 0.001) of the variance in
      adherence, with intentions and past behaviour being the primary factors (P <
      0.05). CONCLUSIONS: RTPs particularly at risk may be those who have a history of
      non-adherence to medical advice, especially when they have negative attitudes
      about IST adherence and feel they have little control over their medication
      taking behaviour. Interventions to improve attitudes about IST adherence and
      control of adherence behaviour are needed.

PMID- 17442742
TI  - Expression of filtrin in human glomerular diseases.
AB  - BACKGROUND: Filtrin (NEPH3/KIRREL2) is a recently characterized member of the
      nephrin-like proteins of the immunoglobulin superfamily, and it has been
      suggested to participate in the maintenance of the glomerular filtration barrier
      in the kidney. In this study, the gene and protein expression of filtrin were
      examined in patients with acquired proteinuric diseases. METHODS: Filtrin mRNA
      levels in renal biopsies were measured with quantitative reverse transcriptase
      polymerase chain reaction (RT-PCR) in two sets of patients with proteinuria. The
      mRNA levels were normalized to the housekeeping gene GAPDH and also related to
      the podocyte-specific genes nephrin and podocin. Immunofluorescence microscopy
      was employed to explore changes in the glomerular distribution of filtrin.
      RESULTS: Reduced glomerular expression of filtrin mRNA was observed in all
      studied diagnostic groups. In focal segmental glomerulosclerosis, the filtrin
      mRNA level was only one-tenth of the control samples (P approximately 5.0x10(
      6)), and this finding was confirmed in a second set of samples. The ratios of
      filtrin to nephrin and podocin demonstrated a marked decrease in the expression
      of filtrin relative to the podocyte marker genes. However, no correlation between
      the expression of filtrin and the levels of serum creatinine and proteinuria was
      observed. Immunostaining showed changes in the expression pattern of filtrin in
      renal biopsies. Immunoelectron microscopic studies localized filtrin at the slit
      diaphragm of the podocyte foot processes. CONCLUSIONS: Down-regulation of the
      filtrin gene and protein expression in the renal biopsies together with the
      localization to the inter-podocyte filtration slit imply a potential role for
      this molecule in the pathogenesis of proteinuric diseases.

PMID- 17442743
TI  - Additive renoprotective effect of candesartan and tetrahydrobiopterin in rats
      after 5/6 nephrectomy.
AB  - BACKGROUND: Chronic treatment with candesartan cilexetil (C) improves the outcome
      of rats after 5/6 nephrectomy (Nx). Tetrahydrobiopterin (BH4), an essential
      cofactor for appropriate endothelial nitric oxide synthase (eNOS) activity,
      prevents an increase in blood pressure (BP) in Nx rats when given immediately
      after surgery. In the present study, we evaluated the renoprotective effect of a
      combined treatment. METHODS: Five groups of rats were studied: SHAM (sham
      operated rats, n=12); SNx (untreated 5/6 nephrectomized rats, n=15); C (SNx rats
      treated with candesartan cilexetil, 5 mg/kg/day per os, n=11); C+BH4 (SNx rats
      treated with candesartan cilexetil and BH4, 10 mg/kg/day intraperitoneally,
      n=11); and BH4 (SNx rats treated with BH4, 10 mg/kg/day intraperitoneally, n=11).
      Treatment began 30 days after surgery, when hypertension and renal insufficiency
      have developed. This day was considered as day 1 of treatment for statistical
      comparisons. The study was continued until 50% mortality was achieved in the SNx
      rats (4 months after surgery). RESULTS: The survival rates were 100% for SHAM,
      47% for SNx, 50% for BH4, 64% for C and 80% for C+BH4 (P<0.05 vs all). Untreated
      Nx rats developed hypertension, proteinuria (UP) and severe renal insufficiency.
      Mortality was associated with a lower renal function and increased urine protein
      excretion. In C and C+BH4 rats, systolic blood pressure (SBP) decreased
      significantly. BH4 alone had a mild non-significant effect on SBP. C and C+BH4
      treatments attenuated significantly the increase in proteinuria found in SNx
      animals. The weight of the remnant kidneys as well as the severity of
      glomerulosclerosis were significantly lower in the C+BH4 rats. CONCLUSION: This
      study shows that in subnephrectomized rats, addition of BH4 to a treatment with
      candesartan had an additive renoprotective effect. The mechanism of such action
      may include a better control of BP associated with a blockade of actions of
      angiotensin II (Ag II), an improvement in nitric oxide synthesis and a balanced
      redox.

PMID- 17442744
TI  - Burnout in health care providers of dialysis service in Northern Italy--a
      multicentre study.
AB  - BACKGROUND: Few data are available regarding the prevalence of burnout among
      dialysis health care workers. Aims of the present study were to assess and
      compare burnout levels in a sample of nurses and physicians working in dialysis
      units, and to investigate their relationships with quality of life, in a cross
      sectional observational study. METHODS: A total of 344 workers from 10 dialysis
      centres in Northern Italy completed a battery of questionnaires including the
      Maslach Burnout Inventory, the MOS-36 Item Short Form Health Survey [SF36:
      physical (PCS) and mental (MCS) component scores] and the 30-item General Health
      Questionnaire (GHQ30). Data on social and demographic characteristics and working
      conditions were also collected. General Estimating Equations models were used for
      the analysis. RESULTS: Overall, burnout scores were lower than the Italian
      normative sample, with no significant differences between physicians and nurses.
      However, 30% of nurses had high emotional exhaustion vs 18% of physicians
      (adjusted OR 2.38, P = 0.003). Emotional exhaustion was also predicted by number
      of worked hours and months worked in dialysis in the previous 2 years.
      Depersonalisation was predicted by male gender and bad relationship with
      coworkers. Having no children and having a permanent hospital position predicted
      low personal accomplishment. PCS was lower in nurses (50.0 vs 53.3, P < 0.001),
      while no significant difference was found for MCS and GHQ30. Lower PCS was
      associated with emotional exhaustion (P = 0.007) and GHQ30 > 5 with
      depersonalization (P = 0.032). CONCLUSIONS: Although burnout is not a general
      problem in dialysis health care providers, a subgroup of them may be identified,
      who would benefit from supportive measures to prevent this condition. Nurses
      appeared more burned-out in the emotional exhaustion scale than physicians.

PMID- 17442745
TI  - A comparison of quality of care indicators in urban acute care hospitals and
      rural critical access hospitals in the United States.
AB  - OBJECTIVE: Two recent Institute of Medicine reports highlight that the quality of
      healthcare in the US is less than what should be expected from the world's most
      extensive and expensive healthcare system. This may be especially true for
      critical access hospitals since these smaller rural-based hospitals often have
      fewer resources and less funding than larger urban hospitals. The purpose of this
      paper was to compare quality of hospital care provided in urban acute care
      hospitals to that provided in rural critical access hospitals. DESIGN: Cross
      sectional study analyzing secondary Hospital Compare data. T-test statistics were
      computed on weighted data to ascertain if differences were statistically
      significant (P=0.01). SETTING: Centers for Medicare and Medicaid Services
      hospitals. PARTICIPANTS: US Acute Care and Critical Access hospitals. MAIN
      OUTCOME MEASURES: Differences between urban acute care hospitals and rural
      critical access hospitals on quality care indicators related to acute myocardial
      infarction, heart failure and pneumonia. RESULTS: For 8 of the 12 hospital
      quality indicators the differences between urban acute care and rural critical
      access hospitals were statistically significant (P=0.01). In seven instances
      these differences favored urban hospitals. One indicator related to pneumonia
      favored rural hospitals CONCLUSIONS: Although this study focused on only three
      disease states, these are among the most common clinical conditions encountered
      in inpatient settings. The findings suggested that there may be differences in
      quality in rural critical access hospitals and urban acute care hospitals and
      support the need for future studies addressing disparities between urban acute
      care and rural critical access hospitals.

PMID- 17442746
TI  - Homozygous SCN5A mutation in Brugada syndrome with monomorphic ventricular
      tachycardia and structural heart abnormalities.
AB  - AIMS: To describe a patient showing monomorphic ventricular tachycardia, ECG
      aspect of Brugada syndrome, and structural heart abnormalities due to a
      homozygous missense mutation in SCN5A. METHODS AND RESULTS: Thirteen subjects
      (six males, seven females, mean age 46 +/- 22 years) belonging to the same family
      underwent physical examination, basal biochemical marker detection, 12-lead ECG,
      Holter ECG, signal-averaged ECG, echocardiogram and genetic analysis. The proband
      underwent a stress test together with left and right ventricular angiography and
      electrophysiological study. Three subjects (the proband, his mother, and one
      brother) showed on ECG an ST-segment elevation in the right precordial leads with
      coved type aspect. Moreover, the proband presented a sustained monomorphic
      ventricular tachycardia (left bundle branch block aspect with superior axis),
      whereas all other family members were asymptomatic. Imaging techniques documented
      right ventricular structural abnormalities only in the proband. Mutation
      screening in SCN5A gene was performed in the proband and in available family
      members. The proband carries a novel SCN5A mutation, R814Q, in homozygous,
      whereas the parents and four siblings were heterozygous carriers of the same
      mutation. CONCLUSION: This study provides the first evidence of a homozygous
      missense mutation in SCN5A associated with atypical ventricular arrhythmias and
      right structural abnormalities.

PMID- 17442747
TI  - Patterning of frontal cortex subdivisions by Fgf17.
AB  - The frontal cortex (FC) is the seat of higher cognition. The genetic mechanisms
      that control formation of the functionally distinct subdivisions of the FC are
      unknown. Using a set of gene expression markers that distinguish subdivisions of
      the newborn mouse FC, we show that loss of Fgf17 selectively reduces the size of
      the dorsal FC whereas ventral/orbital FC appears normal. These changes are
      complemented by a rostral shift of sensory cortical areas. Thus, Fgf17 functions
      similar to Fgf8 in patterning the overall neocortical map but has a more
      selective role in regulating the properties of the dorsal but not ventral FC.

PMID- 17442748
TI  - Systematic discovery of regulatory motifs in conserved regions of the human
      genome, including thousands of CTCF insulator sites.
AB  - Conserved noncoding elements (CNEs) constitute the majority of sequences under
      purifying selection in the human genome, yet their function remains largely
      unknown. Experimental evidence suggests that many of these elements play
      regulatory roles, but little is known about regulatory motifs contained within
      them. Here we describe a systematic approach to discover and characterize
      regulatory motifs within mammalian CNEs by searching for long motifs (12-22 nt)
      with significant enrichment in CNEs and studying their biochemical and genomic
      properties. Our analysis identifies 233 long motifs (LMs), matching a total of
      approximately 60,000 conserved instances across the human genome. These motifs
      include 16 previously known regulatory elements, such as the histone 3'-UTR motif
      and the neuron-restrictive silencer element, as well as striking examples of
      novel functional elements. The most highly enriched motif (LM1) corresponds to
      the X-box motif known from yeast and nematode. We show that it is bound by the
      RFX1 protein and identify thousands of conserved motif instances, suggesting a
      broad role for the RFX family in gene regulation. A second group of motifs (LM2*)
      does not match any previously known motif. We demonstrate by biochemical and
      computational methods that it defines a binding site for the CTCF protein, which
      is involved in insulator function to limit the spread of gene activation. We
      identify nearly 15,000 conserved sites that likely serve as insulators, and we
      show that nearby genes separated by predicted CTCF sites show markedly reduced
      correlation in gene expression. These sites may thus partition the human genome
      into domains of expression.

PMID- 17442749
TI  - Agostic interactions in transition metal compounds.
AB  - The impact of agostic interactions (i.e., 3-center-2-electron M-H-C bonds) on the
      structures and reactivity of organotransition metal compounds is reviewed.

PMID- 17442751
TI  - Theoretical study of the rhenium-alkane interaction in transition metal-alkane
      sigma-complexes.
AB  - Metal-alkane binding energies have been calculated for [CpRe(CO)2](alkane) and
      [(CO)2M(C5H4)C[triple bond]C(C5H4)M(CO)2](alkane), where M = Re or Mn. Calculated
      binding energies were found to increase with the number of metal-alkane
      interaction sites. In all cases examined, the manganese-alkane binding energies
      were predicted to be significantly lower than those for the analogous rhenium
      alkane complexes. The metal (Mn or Re)-alkane interaction was predicted to be
      primarily one of charge transfer, both from the alkane to the metal complex (70
      80% of total charge transfer) and from the metal complex to the alkane (20-30% of
      the total charge transfer).

PMID- 17442750
TI  - The genome of Syntrophus aciditrophicus: life at the thermodynamic limit of
      microbial growth.
AB  - Biochemically, the syntrophic bacteria constitute the missing link in our
      understanding of anaerobic flow of carbon in the biosphere. The completed genome
      sequence of Syntrophus aciditrophicus SB, a model fatty acid- and aromatic acid
      degrading syntrophic bacterium, provides a glimpse of the composition and
      architecture of the electron transfer and energy-transducing systems needed to
      exist on marginal energy economies of a syntrophic lifestyle. The genome contains
      3,179,300 base pairs and 3,169 genes where 1,618 genes were assigned putative
      functions. Metabolic reconstruction of the gene inventory revealed that most
      biosynthetic pathways of a typical Gram-negative microbe were present. A
      distinctive feature of syntrophic metabolism is the need for reverse electron
      transport; the presence of a unique Rnf-type ion-translocating electron transfer
      complex, menaquinone, and membrane-bound Fe-S proteins with associated
      heterodisulfide reductase domains suggests mechanisms to accomplish this task.
      Previously undescribed approaches to degrade fatty and aromatic acids, including
      multiple AMP-forming CoA ligases and acyl-CoA synthetases seem to be present as
      ways to form and dissipate ion gradients by using a sodium-based energy strategy.
      Thus, S. aciditrophicus, although nutritionally self-sufficient, seems to be a
      syntrophic specialist with limited fermentative and respiratory metabolism.
      Genomic analysis confirms the S. aciditrophicus metabolic and regulatory
      commitment to a nonconventional mode of life compared with our prevailing
      understanding of microbiology.

PMID- 17442752
TI  - Dihydrogen complexes as prototypes for the coordination chemistry of saturated
      molecules.
AB  - The binding of a dihydrogen molecule (H(2)) to a transition metal center in an
      organometallic complex was a major discovery because it changed the way chemists
      think about the reactivity of molecules with chemically "inert" strong bonds such
      as H H and C H. Before the seminal finding of side-on bonded H(2) in
      W(CO)(3)(PR(3))(2)(H(2)), it was generally believed that H(2) could not bind to
      another atom in stable fashion and would split into two separate H atoms to form
      a metal dihydride before undergoing chemical reaction. Metal-bound saturated
      molecules such as H(2), silanes, and alkanes (sigma-complexes) have a chemistry
      of their own, with surprisingly varied structures, bonding, and dynamics. H(2)
      complexes are of increased relevance for H(2) production and storage in the
      hydrogen economy of the future.

PMID- 17442753
TI  - Coherent neural representation of hand speed in humans revealed by MEG imaging.
AB  - The spiking activity of single neurons in the primate motor cortex is correlated
      with various limb movement parameters, including velocity. Recent findings
      obtained using local field potentials suggest that hand speed may also be encoded
      in the summed activity of neuronal populations. At this macroscopic level, the
      motor cortex has also been shown to display synchronized rhythmic activity
      modulated by motor behavior. Yet whether and how neural oscillations might be
      related to limb speed control is still poorly understood. Here, we applied
      magnetoencephalography (MEG) source imaging to the ongoing brain activity in
      subjects performing a continuous visuomotor (VM) task. We used coherence and
      phase synchronization to investigate the coupling between the estimated activity
      throughout the brain and the simultaneously recorded instantaneous hand speed. We
      found significant phase locking between slow (2- to 5-Hz) oscillatory activity in
      the contralateral primary motor cortex and time-varying hand speed. In addition,
      we report long-range task-related coupling between primary motor cortex and
      multiple brain regions in the same frequency band. The detected large-scale VM
      network spans several cortical and subcortical areas, including structures of the
      frontoparietal circuit and the cerebello-thalamo-cortical pathway. These findings
      suggest a role for slow coherent oscillations in mediating neural representations
      of hand kinematics in humans and provide further support for the putative role of
      long-range neural synchronization in large-scale VM integration. Our findings are
      discussed in the context of corticomotor communication, distributed motor
      encoding, and possible implications for brain-machine interfaces.

PMID- 17442754
TI  - Nonmammalian orthologs of prestin (SLC26A5) are electrogenic divalent/chloride
      anion exchangers.
AB  - Individual members of the mammalian SLC26 anion transporter family serve two
      fundamentally distinct functions. Whereas most members transport different anion
      substrates across a variety of epithelia, prestin (SLC26A5) is special,
      functioning as a membrane-localized motor protein that generates electrically
      induced motions (electromotility) in auditory sensory hair cells of the mammalian
      inner ear. The transport mechanism of SLC26 proteins is not well understood, and
      a mechanistic relation between anion transport and electromotility has been
      suggested but not firmly established so far. To address these questions, we have
      cloned prestin orthologs from chicken and zebrafish, nonmammalian vertebrates
      that presumably lack electromotility in their auditory systems. Using patch-clamp
      recordings, we show that these prestin orthologs, but not mammalian prestin,
      generate robust transport currents in the presence of the divalent anions sulfate
      or oxalate. Transport is blocked by salicylate, an inhibitor of electromotility
      generated by mammalian prestin. The dependence of transport equilibrium
      potentials on sulfate and chloride concentration gradients shows that the prestin
      orthologs are electrogenic antiporters, exchanging sulfate or oxalate for
      chloride in a strictly coupled manner with a 1:1 stoichiometry. These data
      identify transport mode and stoichiometry of electrogenic divalent/monovalent
      anion exchange and establish a reliable and simple method for the quantitative
      determination of the various transport modes that have been proposed for other
      SLC26 transport proteins. Moreover, the sequence conservation between mammalian
      and nonmammalian prestin together with a common pharmacology of electromotility
      and divalent antiport suggest that the molecular mechanism behind electromotility
      is closely related to an anion transport cycle.

PMID- 17442755
TI  - Phase-separation in ion-containing mixtures in electric fields.
AB  - When a liquid mixture is subjected to external electric fields, ionic screening
      leads to field gradients. We point out that, if the mixture is initially in the
      homogeneous phase, this screening can bring about a robust phase-separation
      transition with two main features: (i) the phase separation is expected to occur
      in any electrode geometry, and (ii) the voltage required is typically of the
      order of 1 V and even less. We discuss several applications of the effect
      relevant to the field of microfluidics, focusing on the creation of a nanometer
      scale lubrication layer in the phase separation process and the modification of
      the slip length.

PMID- 17442756
TI  - Diversity in prion protein oligomerization pathways results from domain expansion
      as revealed by hydrogen/deuterium exchange and disulfide linkage.
AB  - The prion protein (PrP) propensity to adopt different structures is a clue to its
      biological role. PrP oligomers have been previously reported to bear prion
      infectivity or toxicity and were also found along the pathway of in vitro amyloid
      formation. In the present report, kinetic and structural analysis of ovine PrP
      (OvPrP) oligomerization showed that three distinct oligomeric species were formed
      in parallel, independent kinetic pathways. Only the largest oligomer gave rise to
      fibrillar structures at high concentration. The refolding of OvPrP into these
      different oligomers was investigated by analysis of hydrogen/deuterium exchange
      and introduction of disulfide bonds. These experiments revealed that, before
      oligomerization, separation of contacts in the globular part (residues 127-234)
      occurred between the S1-H1-S2 domain (residues 132-167) and the H2-H3 bundle
      (residues 174-230), implying a conformational change of the S2-H2 loop (residues
      168-173). The type of oligomer to be formed depended on the site where the
      expansion of the OvPrP monomer was initiated. Our data bring a detailed insight
      into the earlier conformational changes during PrP oligomerization and account
      for the diversity of oligomeric entities. The kinetic and structural mechanisms
      proposed here might constitute a physicochemical basis of prion strain genesis.

PMID- 17442757
TI  - Molecular characteristics of rifampicin- and isoniazid-resistant Mycobacterium
      tuberculosis isolates from the Russian Federation.
AB  - OBJECTIVES: Three Mycobacterium tuberculosis genetic loci--rpoB and katG genes
      and the fabG1(mabA)-inhA operon promoter region--were studied to reveal the
      mutations associated with rifampicin and isoniazid resistance. METHODS: Four
      hundred and twelve isolates of M. tuberculosis from different regions of the
      Russian Federation were collected during 1997-2005. A matrix-assisted laser
      desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS)-based
      minisequencing method was used for the detection of mutations. RESULTS: Thirteen
      different variants of single mutations in codons 533, 531, 526, 516, 513 and 511
      of the rifampicin resistance-determining region of the rpoB gene as well as the
      TTG insertion in the 514a position were found among the rifampicin-resistant
      isolates. Single nucleotide substitutions in codons 531, 526 and 516 (64.8%,
      10.3% and 7.7%, respectively) were the most prevalent mutations. Codon 526 was
      shown to be the most variable of all. No mutations were detected in rpoB genes
      for 29 (10.7%) of the rifampicin-resistant isolates. 76.9% of the isoniazid
      resistant isolates carried single mutations in codon 315 of the katG gene. For
      another 12.9% of them, double mutations in the katG gene and the fabG1(mabA)-inhA
      promoter region were revealed. No mutations were detected in 8.2% of the
      isoniazid-resistant isolates. CONCLUSIONS: Molecular analysis of the loci of rpoB
      and katG genes and the inhA promoter region of 412 M. tuberculosis clinical
      isolates from various parts of the Russian Federation was carried out. The new
      MALDI-TOF MS-based method may be used for rapid and accurate monitoring of the
      spread of drug resistance.

PMID- 17442758
TI  - APP locus duplication in a Finnish family with dementia and intracerebral
      haemorrhage.

PMID- 17442759
TI  - Cognitive impairment in Parkinson's disease.
AB  - BACKGROUND: Cognitive impairment plays a role in Parkinson's disease (PD) and has
      important consequences for patient management. However, many aspects of cognitive
      impairment in PD remain unclear because of the use of different and often invalid
      measurement instruments. In this study, a reliable and valid instrument, the
      SCales for Outcomes in PArkinson's disease-COGnition (SCOPA-COG), was used. AIM:
      To evaluate cognitive functioning in a large cohort of patients with Parkinson's
      disease and to assess the relations with demographic, disease related and
      clinical variables. METHODS: A cohort of 400 patients with PD was evaluated for
      cognition, motor and non-motor domains, as well as for demographic and disease
      related characteristics. Results were compared with 150 controls matched for
      overall age, sex and education distribution. RESULTS: Patients with PD scored
      significantly lower on all cognitive subdomains compared with controls, with the
      largest differences for executive functioning and memory. After correction for
      age and years of education, 22% of patients had impaired cognition, as measured
      by the total SCOPA-COG score, compared with controls. Across all patients, more
      severe cognitive impairment was associated with significantly more impairment in
      motor, autonomic, depressive and psychotic domains. Patients with the postural
      instability gait difficulty (PIGD) dominant phenotype showed more cognitive
      impairment compared with patients with the tremor dominant phenotype. Contrary to
      tremor scores, PIGD scores significantly worsened with increasing disease
      severity. CONCLUSIONS: Cognition is an important domain of the clinical spectrum
      of PD and poorer cognitive performance is associated with greater impairment in
      motor and non-motor domains in PD. The difference in cognitive scores between
      PIGD dominant patients and tremor dominant patients likely reflects more advanced
      disease.

PMID- 17442760
TI  - Effect of electrode contact location on clinical efficacy of pallidal deep brain
      stimulation in primary generalised dystonia.
AB  - OBJECTIVES: To determine the effect of electrode contact location on efficacy of
      bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) for primary
      generalised dystonia (PGD). SUBJECTS AND METHODS: A consecutive series of 15
      patients with PGD (10 females, mean age 42 years, seven DYT1) who underwent
      bilateral GPi DBS, were assessed using the Burke-Fahn-Marsden (BFM) dystonia
      scale before and 6 months after surgery. The position of the stimulated electrode
      contact(s) was determined from the postoperative stereotactic MRI. Contralateral
      limb and total axial BFM subscores were compared with the location of the
      stimulated contact(s) within the GPi. RESULTS: The mean total BFM score decreased
      from 38.9 preoperatively to 11.9 at 6 months, an improvement of 69.5%
      (p<0.00001). Cluster analysis of the stimulated contact coordinates identified
      two groups, distributed along an anterodorsal to posteroventral axis. Clinical
      improvement was greater for posteroventral than anterodorsal stimulation for the
      arm (86% vs 52%; p<0.05) and trunk (96% vs 65%; p<0.05) and inversely correlated
      with the y coordinate. For the leg, posteroventral and anterodorsal stimulation
      were of equivalent efficacy. Overall clinical improvement was maximal with
      posteroventral stimulation (89% vs 67%; p<0.05) and inversely correlated with the
      y (A-P) coordinate (r = -0.62, p<0.05). CONCLUSION: GPi DBS is effective for PGD
      but outcome is dependent on contact location. Posteroventral GPi stimulation
      provides the best overall effect and is superior for the arm and trunk. These
      results may be explained by the functional anatomy of GPi and its outflow tracts.

PMID- 17442761
TI  - Chronic cluster headache: a French clinical descriptive study.
AB  - BACKGROUND: Cluster headache (CH) is a relatively rare disease and episodic CH is
      more frequent than chronic CH. Few studies have described the characteristics of
      patients with chronic CH. METHODS: This was a descriptive study carried out by
      eight tertiary care specialist headache centres in France participating in the
      Observatory of Migraine and Headaches (OMH). From 2002 to 2005, OMH collected
      data from 2074 patients with CH, of whom 316 had chronic CH. From January to June
      2005, 113 patients with chronic CH were interviewed using standardised
      questionnaires during a consultation. RESULTS: The male to female ratio was
      4.65:1. Median age was 42 years. The majority of patients were smokers or former
      smokers (87%). 46% had primary chronic CH (chronic at onset) and 54% secondary
      chronic CH (evolving from episodic CH). Most patients had unilateral pain during
      attacks and 7% had sometimes bilateral pain during an attack. 48% reported a
      persisting painful state between attacks. Symptoms anteceding pain onset (mainly
      discomfort/diffuse pain, exhaustion, mood disorders) and auras were reported by
      55% and 20% of patients, respectively. The functional impact of chronic CH was
      estimated as severe by 74% of patients, and 75.7% suffered from anxiety, as
      assessed by the Hospital Anxiety and Depression scale. There was no substantial
      difference in clinical presentation between primary and secondary CH. DISCUSSION:
      This study confirms the existence of auras and interictal signs and symptoms in
      patients with chronic CH, and male sex and smoking as CH risk factors. Primary
      and secondary chronic CH appear equally prevalent. Male sex does not appear to
      favour the shift from episodic to chronic CH.

PMID- 17442762
TI  - The 39 item Parkinson's disease questionnaire (PDQ-39) revisited: implications
      for evidence based medicine.
AB  - BACKGROUND: The 39 item Parkinson's disease questionnaire (PDQ-39) is the most
      widely used patient reported rating scale in Parkinson's disease. However,
      several fundamental measurement assumptions necessary for confident use and
      interpretation of the eight PDQ-39 scales have not been fully addressed. METHODS:
      Postal survey PDQ-39 data from 202 people with Parkinson's disease (54% men; mean
      age 70 years) were analysed regarding psychometric properties using traditional
      and Rasch measurement methods. RESULTS: Data quality was good (mean missing item
      responses, 2%) and there was general support for the legitimacy of summing items
      within scales without weighting or standardisation. Score reliabilities were
      adequate (Cronbach's alpha 0.72-0.95; test-retest 0.76-0.93). The validity of the
      current grouping of items into scales was not supported by scaling success rates
      (mean 56.2%), or factor and Rasch analyses. All scales represented more health
      problems than that experienced by the sample (mean floor effect 15%) and showed
      compromised score precision towards the less severe end. CONCLUSIONS: Our results
      provide general support for the acceptability and reliability of the PDQ-39.
      However, they also demonstrate limitations that have implications for the use of
      the PDQ-39 in clinical research. The grouping of items into scales appears overly
      complex and the meaning of scale scores is unclear, which hampers their
      interpretation. Suboptimal targeting limits measurement precision and, therefore,
      probably also responsiveness. These observations have implications for the role
      of the PDQ-39 in clinical trials and evidence based medicine. PDQ-39 derived
      endpoints should be interpreted and selected cautiously, particularly regarding
      small but clinically important effects among people with less severe problems.

PMID- 17442763
TI  - Measuring cognitive change in older adults: reliable change indices for the Mini
      Mental State Examination.
AB  - BACKGROUND: In clinical and research settings, the Mini-Mental State Examination
      (MMSE) is commonly used to measure cognitive change over time. The interpretation
      of changes in MMSE is often difficult. They do not necessarily result from true
      clinical change. Their interpretation requires comparison with normative data for
      change. However, MMSE change norms are lacking for long intervals. OBJECTIVE: To
      examine what is a reliable change in MMSE for long follow-up periods commonly
      used in clinic. To provide normative data for change. METHODS: A sample of 119
      cognitively normal individuals, aged 75 years and over, who participated in the
      Leipzig Longitudinal Study of the Aged (LEILA 75+). All participants were tested
      six times at 1.5 year intervals with the MMSE over a mean period of 7.1 years.
      Reliable change indices were computed for a common confidence interval (90%).
      RESULTS: In repeated assessments with 1.5 year intervals, a change in MMSE of at
      least 2-4 points indicated a reliable change at the 90% confidence level.
      CONCLUSION: Small changes in MMSE can be interpreted only with great uncertainty.
      They have a reasonable probability of being caused by measurement error,
      regression to the mean or practice.

PMID- 17442764
TI  - Activity changes in monkey superior colliculus during saccade adaptation.
AB  - Saccades are eye movements that are used to foveate targets rapidly and
      accurately. Their amplitude must be adjusted continually, throughout life, to
      compensate for movement inaccuracies due to maturation, pathology, or aging. One
      possible locus for such saccade adaptation is the superior colliculus (SC), the
      relay for cortical commands to the premotor brain stem generator for saccades.
      However, previous stimulation and recording studies have disagreed as to whether
      saccade adaptation occurs up- or downstream of the SC. Therefore we have
      reexamined the behavior of SC burst neurons during saccade adaptation under
      conditions that were optimized to produce the biggest possible change in neuronal
      activity. We show that behavioral adaptation of saccade amplitude was associated
      with significant increases or decreases, in the number of spikes in the burst
      and/or changes in the shape of the movement field in 35 of 43 SC neurons tested.
      Of the 35, 29 had closed movement fields and 14 were classified indeterminate
      because the movement field could not be definitively diagnosed. Changes in the
      number of spikes occurred gradually during adaptation and resulted from
      correlated changes in burst lead and duration without consistent changes in peak
      burst rate. These data indicate that the great majority of SC neurons show a
      change in discharge in association with saccade amplitude adaptation. Based on
      these and previous results, we speculate that the site for saccade adaptation
      resides in the SC or that the SC is the final common pathway for adaptive changes
      that occur elsewhere in the saccade system.

PMID- 17442765
TI  - Development of cholinergic modulation and graded persistent activity in layer v
      of medial entorhinal cortex.
AB  - During muscarinic modulation, principal neurons from layer V of rat medial
      entorhinal cortex (mEC) respond to repeated applications of a brief stimulus with
      a graded change in persistent firing frequency. This pattern of discharge has
      been proposed to represent an intrinsic mechanism for short-term memory
      operations. To investigate the implementation of persistent activity in mEC
      during development, we characterized the electrophysiological properties of layer
      V principal neurons in the mEC over a range of postnatal stages. We observed
      significant differences in both passive (resistance, time constant, and resting
      membrane potential) and active properties (threshold, action potential, and
      adaptation) of principal neurons from rats aged 5-7, 10-13, 16-19, and 21-23
      days. We also examined the properties of muscarinic-dependent persistent activity
      in EC slices from different age groups. Recordings were conducted using the
      perforated-patch whole cell technique because persistent activity runs down in
      the ruptured-patch configuration. Although no neuron in the youngest group
      exhibited graded persistent activity in response to muscarinic receptor
      activation, this activity was recorded in the 10- to 13-day-old group and its
      occurrence increased from 69% in the 16- to 19-day-old group to 76% in the 21- to
      23-day-old group. This postnatal increase in neurons endowed with persistent
      firing properties in mEC was found to parallel the increase in density of ChAT
      positive immunostaining of fibers and the developmental changes in M1 muscarinic
      receptor mRNA levels. All these data suggest that the implementation of mnemonic
      properties in mEC principal neurons matches the ontogenic development of afferent
      cholinergic circuits and their signaling components.

PMID- 17442766
TI  - Human visuospatial updating after noncommutative rotations.
AB  - As we move our bodies in space, we often undergo head and body rotations about
      different axes-yaw, pitch, and roll. The order in which we rotate about these
      axes is an important factor in determining the final position of our bodies in
      space because rotations, unlike translations, do not commute. Does our brain keep
      track of the noncommutativity of rotations when computing changes in head and
      body orientation and then use this information when planning subsequent motor
      commands? We used a visuospatial updating task to investigate whether saccades to
      remembered visual targets are accurate after intervening, whole-body rotational
      sequences. The sequences were reversed, either yaw then roll or roll then yaw,
      such that the final required eye movements to reach the same space-fixed target
      were different in each case. While each subject performed consistently
      irrespective of target location and rotational combination, we found great
      intersubject variability in their capacity to update. The distance between the
      noncommutative endpoints was, on average, half of that predicted by perfect
      noncommutativity. Nevertheless, most subjects did make eye movements to distinct
      final endpoint locations and not to one unique location in space as predicted by
      a commutative model. In addition, their noncommutative performance significantly
      improved when their less than ideal updating performance was taken into account.
      Thus the brain can produce movements that are consistent with the processing of
      noncommutative rotations, although it is often poor in using internal estimates
      of rotation for updating.

PMID- 17442768
TI  - Processing of bile salt odor information by single olfactory bulb neurons in the
      channel catfish.
AB  - A chemotopic map of biologically relevant odorants (that include amino acids,
      bile salts, and nucleotides) exists in the olfactory bulb (OB) of channel
      catfish, Ictalurus punctatus. Neurons processing bile salt odorant information
      lie medially within this OB map; however, information as to how single neurons
      process bile salt odorant information is lacking. In the present report,
      recordings were obtained from 51 OB neurons from 30 channel catfish to determine
      the excitatory molecular receptive range (EMRR) of bile salt responsive neurons.
      All recordings were performed in vivo within the medial portions of the OB using
      extracellular electrophysiological techniques. Excitatory thresholds to bile
      salts typically ranged between 0.1 and 10 muM. The bile salt specificity of OB
      neurons were divided into three groups: neurons excited by taurine-conjugated
      bile salts only (group T), neurons excited by nonconjugated bile salts only
      (group N), and neurons excited by at least one member of each of the three
      classes of bile salts tested (group G). In addition to the conjugating group at
      C24 of the side-chain, OB neurons discriminated bile salts by the molecular
      features present at three other carbon positions (C3, C7, and C12) along the
      steroid backbone. These data suggest that OB neurons are selectively excited by
      combinations of molecular features found on the side-chain and along the steroid
      nucleus of bile salt molecules.

PMID- 17442767
TI  - Action potential timing precision in dorsal cochlear nucleus pyramidal cells.
AB  - Many studies of the dorsal cochlear nucleus (DCN) have focused on the
      representation of acoustic stimuli in terms of average firing rate. However,
      recent studies have emphasized the role of spike timing in information encoding.
      We sought to ascertain whether DCN pyramidal cells might employ similar
      strategies and to what extent intrinsic excitability regulates spike timing.
      Gaussian distributed low-pass noise current was injected into pyramidal cells in
      a brain slice preparation. The shuffled autocorrelation-based analysis was used
      to compute a correlation index of spike times across trials. The noise causes the
      cells to fire with temporal precision (SD congruent with 1-2 ms) and high
      reproducibility. Increasing the coefficient of variation of the noise improved
      the reproducibility of the spike trains, whereas increasing the firing rate of
      the neuron decreased the neurons' ability to respond with predictable patterns of
      spikes. Simulated inhibitory postsynaptic potentials superimposed on the noise
      stimulus enhanced spike timing for >300 ms, although the enhancement was greatest
      during the first 100 ms. We also found that populations of pyramidal neurons
      respond to the same noise stimuli with correlated spike trains, suggesting that
      ensembles of neurons in the DCN receiving shared input can fire with similar
      timing. These results support the hypothesis that spike timing can be an
      important aspect of information coding in the DCN.

PMID- 17442769
TI  - A neural model of figure-ground organization.
AB  - Psychophysical studies suggest that figure-ground organization is a largely
      autonomous process that guides--and thus precedes--allocation of attention and
      object recognition. The discovery of border-ownership representation in single
      neurons of early visual cortex has confirmed this view. Recent theoretical
      studies have demonstrated that border-ownership assignment can be modeled as a
      process of self-organization by lateral interactions within V2 cortex. However,
      the mechanism proposed relies on propagation of signals through horizontal
      fibers, which would result in increasing delays of the border-ownership signal
      with increasing size of the visual stimulus, in contradiction with experimental
      findings. It also remains unclear how the resulting border-ownership
      representation would interact with attention mechanisms to guide further
      processing. Here we present a model of border-ownership coding based on dedicated
      neural circuits for contour grouping that produce border-ownership assignment and
      also provide handles for mechanisms of selective attention. The results are
      consistent with neurophysiological and psychophysical findings. The model makes
      predictions about the hypothetical grouping circuits and the role of feedback
      between cortical areas.

PMID- 17442770
TI  - Chemical factors determine olfactory system beta oscillations in waking rats.
AB  - Recent studies have pointed to olfactory system beta oscillations of the local
      field potential (15-30 Hz) and their roles both in learning and as specific
      responses to predator odors. To describe odorant physical properties, resultant
      behavioral responses and changes in the central olfactory system that may induce
      these oscillations without associative learning, we tested rats with 26
      monomolecular odorants spanning 6 log units of theoretical vapor pressure
      (estimate of relative vapor phase concentration) and 10 different odor mixtures.
      We found odorant vapor phase concentration to be inversely correlated with
      investigation time on the first presentation, after which investigation times
      were brief and not different across odorants. Analysis of local field potentials
      from the olfactory bulb and anterior piriform cortex shows that beta oscillations
      in waking rats occur specifically in response to the class of volatile organic
      compounds with vapor pressures of 1-120 mmHg. Beta oscillations develop over the
      first three to four presentations and are weakly present for some odorants in
      anesthetized rats. Gamma oscillations show a smaller effect that is not
      restricted to the same range of odorants. Olfactory bulb theta oscillations were
      also examined as a measure of effective afferent input strength, and the power of
      these oscillations did not vary systematically with vapor pressure, suggesting
      that it is not olfactory bulb drive strength that determines the presence of beta
      oscillations. Theta band coherence analysis shows that coupling strength between
      the olfactory bulb and piriform cortex increases linearly with vapor phase
      concentration, which may facilitate beta oscillations above a threshold.

PMID- 17442771
TI  - Presynaptic inhibition of excitatory afferents to hilar mossy cells.
AB  - The hippocampus contains one very strong recurrent excitatory network formed by
      associational connections between CA3 pyramidal cells and another that depends
      largely on a disynaptic excitatory pathway between dentate granule cells. The
      recurrent excitatory network in CA3 has long been considered a possible location
      of autoassociative memory storage, whereas changes in the level and arrangement
      of recurrent excitation between granule cells are strongly implicated in
      epileptogenesis. Hilar mossy cells are likely to receive collateral input from
      CA3 pyramidal cells and they are key intermediaries (by mossy fiber inputs) in
      the recurrent excitatory network between granule cells. The current study uses
      minimal stimulation techniques in an in vitro preparation of the rat dentate
      gyrus to examine presynaptic modulation of both mossy fiber and non-mossy fiber
      inputs to hilar mossy cells. We report that both mossy fiber and non-mossy fiber
      inputs to hilar mossy cells express presynaptic gamma-aminobutyric acid type B
      (GABA(B)) receptors that are subject to tonic inhibition by ambient GABA. We
      further find that only non-mossy fiber inputs express presynaptic muscarinic
      acetylcholine receptors, but that bath application of cholinergic agonists
      produces action potential-dependent increases in ambient GABA that can indirectly
      inhibit mossy fiber inputs. Finally, we demonstrate that mossy cells express high
      affinity postsynaptic GABA(A) receptors that are also capable of detecting
      changes in ambient GABA produced by cholinergic agonists. Our results are among
      the first to directly characterize these important collateral inputs to hilar
      mossy cells and may help facilitate informed comparison between primary and
      collateral projections in two major excitatory pathways.

PMID- 17442772
TI  - Cytokine signaling, lipid raft clustering, and HSC hibernation.
AB  - Hematopoietic stem cells (HSCs) reside in the bone marrow (BM) niche in a
      noncycling state and enter the cell cycle at long intervals. This unique property
      of HSCs is reminiscent of hibernation in mammals. However, little is known about
      inter- and intracellular signaling mechanisms underlying this unique property of
      HSCs. This is largely due to the paucity of HSCs making application of
      traditional signal transduction assays difficult. To address these issues, we
      have developed a novel assay based on in-droplet single-cell staining and
      quantitative fluorescence imaging analysis. Using this assay system, we
      demonstrate that freshly isolated HSCs from the BM niche lack lipid raft
      clustering, exhibit repression of the AKT-FOXO signaling pathway, and express
      abundant p57(Kip2) cyclin-dependent kinase inhibitor. Lipid raft clustering
      induced by cytokines was essential for HSC re-entry into the cell cycle.
      Conversely, inhibition of lipid raft clustering caused sustained nuclear
      accumulation of FOXO transcription factors and induced HSC hibernation ex vivo.
      Among niche signals examined, transforming growth factor-beta (TGF-beta)
      efficiently inhibited lipid raft clustering and induced p57(Kip2) expression,
      leading to HSC hibernation. These data uncover a critical role for lipid rafts in
      HSC fate decision and establish the role of TGF-beta as a niche signal in control
      of HSC hibernation in the BM niche.

PMID- 17442773
TI  - NUP98 dysregulation in myeloid leukemogenesis.
AB  - Nucleoporin 98 (NUP98) is a component of the nuclear pore complex that
      facilitates mRNA export from the nucleus. It is mapped to 11p15.5 and is fused to
      a number of distinct partners, including nine members of the homeobox family as a
      consequence of leukemia-associated chromosomal translocations. NUP98-HOXA9 is
      associated with the t(7;11)(p15;p15) translocation in acute myeloid leukemia
      (AML), myelodysplastic syndrome, and blastic crisis of chronic myeloid leukemia.
      Expression of NUP98-HOXA9 in murine bone marrow resulted in a myeloproliferative
      disease progressing to AML by 7-8 months. Transduction of NUP98 fusion genes into
      human CD34(+) cells confers a proliferative advantage in long-term cytokine
      stimulated and stromal cocultures and in NOD-SCID engrafted mice, associated with
      a five- to eight-fold increase in hematopoietic stem cells. NUP98-HOXA9
      expression inhibited erythroid and myeloid differentiation but enhanced serial
      progenitor replating. NUP98-HOXA9 upregulated a number of homeobox genes of the A
      and B cluster as well as MEIS1 and Pim-1, and downmodulated globin genes and
      C/EBPalpha. The HOXA9 component of the NUP98-HOXA9 fusion protein was protected
      from cullin-4A-mediated ubiquitination and subsequent proteasome-dependent
      degradation. In NUP98-HOX-transduced CD34(+) cells and cells from AML patients
      with t(7;11)(p15;p15) NUP98 was no longer associated with the nuclear pore
      complex but formed intranuclear aggregation bodies. Analysis of NUP98 allelic
      expression in AML and myelodysplastic syndrome showed loss of heterozygosity
      observed in 29% of the former and 8% of the latter. This was associated with poor
      prognosis.

PMID- 17442774
TI  - Feasibility and outcome of reduced-intensity conditioning in haploidentical
      transplantation.
AB  - Allogeneic stem cell transplantation is for a number of patients with malignant
      and nonmalignant diseases the only curative approach. For those patients who do
      not have an HLA-identical-related or -unrelated stem cell donor, a related three
      loci mismatch haploidentical stem cell transplantation with T cell-depleted stem
      cells is a viable option. T cell depletion either by CD34(+) positive selection
      or by CD3-negative depletion strategies is available and has been investigated.
      We have shown that reduced-intensity conditioning haploidentical transplantation
      using mobilized peripheral stem cells negatively depleted from T and B
      lymphocytes is associated with a rapid immune reconstitution, a low transplant
      related mortality rate, and a favorable outcome in patients in remission at the
      time of transplant. For chemorefractory patients, additional posttransplant
      cellular and humoral immunotherapeutic strategies are needed for prevention of
      relapse after transplantation.

PMID- 17442775
TI  - Inference, validation, and dynamic modeling of transcription networks in
      multipotent hematopoietic cells.
AB  - Identifying the transcription factor interactions that are responsible for cell
      specific gene expression programs is key to understanding the regulation of cell
      behaviors, such as self-renewal, proliferation, differentiation, and death. The
      rapidly increasing availability of microarray-derived global gene expression data
      sets, coupled with genome sequence information from multiple species, has driven
      the development of computational methods to reverse engineer and dynamically
      model genetic regulatory networks. An understanding of the architecture and
      behavior of transcriptional networks should lend insight into how the huge number
      of potential gene expression programs is constrained and facilitates efforts to
      direct or redirect cell fate.

PMID- 17442776
TI  - Modulation of immune responses by mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are multipotent progenitor cells and interest in
      MSC therapy has been raised by the observation that MSCs are able to modulate
      immune responses in vitro and in vivo. Here, we show that MSCs are not
      intrinsically immune privileged and are capable of inducing memory T cell
      responses following injection in vivo in immunocompetent hosts. After
      cotransplantation in recipients that have received sublethal irradiation,
      allogeneic MSCs can still induce an alloresponse that may result in graft
      rejection, suggesting that the immunogenicity of allogeneic MSCs are not fully
      prevented by a nonmyeloablative conditioning regimen. It is still unclear whether
      the immunogenicity of allogeneic MSCs is also preserved following a fully
      myeloablative conditioning regimen.

PMID- 17442777
TI  - Biological and molecular evidence for existence of lymphoid-primed multipotent
      progenitors.
AB  - Studies from our and other laboratories have over the last 2 years implicated the
      existence of multipotent progenitors (MPPs) with combined granulocyte-macrophage,
      B cell, and T cell potential, but little or no megakaryocyte-erythroid (MkE)
      potential in the adult bone marrow Lineage(-)SCA-1(+)KIT(+) (LSK) compartment of
      multipotent stem and progenitor cells. The evidence for the existence of
      LSKCD34(+)FLT3(hi) lymphoid-primed MPPs (LMPPs) implicates that a strict
      separation into common myeloid and lymphoid pathways might not be the first
      lineage commitment step of hematopoietic stem cells (HSCs). Together with the
      evidence for existence of common myeloid and common lymphoid progenitors (CMPs
      and CLPs, respectively), the identification of LMPPs also suggests that at least
      the granulocyte-macrophage lineage can be generated through alternative pathways.
      However, the existence of LMPPs has recently been questioned, as there is
      evidence that at least a fraction of LSKCD34(+)FLT3(hi) cells sustains MkE
      potential. Thus, in more recent studies we have in more detail compared the
      molecular signature of adult LMPPs to populations of LSK cells enriched for cells
      with pluripotent HSC activity. Notably, we have found at the global as well as
      single-cell level that LMPPs when compared with pluripotent HSCs downregulate the
      transcriptional priming of genes typically expressed in cells of the MkE lineage,
      while upregulating early lymphoid genes. Although other studies have suggested
      that the earliest HSC commitment steps might differ in fetal and adult
      hematopoiesis, we have also obtained evidence suggesting that the LMPP is defined
      already during fetal development.

PMID- 17442778
TI  - Dormant and self-renewing hematopoietic stem cells and their niches.
AB  - In the mouse, over the last 20 years, a set of cell-surface markers and
      activities have been identified, enabling the isolation of bone marrow (BM)
      populations highly enriched in hematopoietic stem cells (HSCs). These HSCs have
      the ability to generate multiple lineages and are capable of long-term self
      renewal activity such that they are able to reconstitute and maintain a
      functional hematopoietic system after transplantation into lethally irradiated
      recipients. Using single-cell reconstitution assays, various marker combinations
      can be used to achieve a functional HSC purity of almost 50%. Here we have used
      the differential expression of six of these markers (Sca1, c-Kit, CD135, CD48,
      CD150, and CD34) on lineage-depleted BM to refine cell hierarchies within the HSC
      population. At the top of the hierarchy, we propose a dormant HSC population
      (Lin(-)Sca1(+)c-Kit(+) CD48(-)CD150(+)CD34(-)) that gives rise to an active self
      renewing CD34(+) HSC population. HSC dormancy, as well as the balance between
      self-renewal and differentiation activity, is at least, in part, controlled by
      the stem cell niches individual HSCs are attached to. Here we review the current
      knowledge about HSC niches and propose that dormant HSCs are located in niches at
      the endosteum, whereas activated HSCs are in close contact to sinusoids of the BM
      microvasculature.

PMID- 17442779
TI  - Effect of FLT3 inhibition on normal hematopoietic progenitor cells.
AB  - Ligand-mediated activation of the FMS-like tyrosine kinase-3 (FLT3) receptor is
      important for normal proliferation of primitive hematopoietic cells. FLT3
      expression in the bone marrow is restricted to CD34(+) cells and a subset of
      dendritic precursors. FLT3, as a member of the type III RTK subfamily, is closely
      related to c-kit, c-FMS, and PDGFalpha/beta and is an unspecific target of
      tyrosine kinase inhibitors, such as imatinib. Activating mutations of FLT3 play
      an important role in leukemogenesis and their presence is associated with poor
      prognosis in acute myeloid leukemia (AML). Targeting the mutation by inhibiting
      the tyrosine kinase activity of FLT3 is a promising therapeutic option in the
      treatment of AML patients. CEP-701 (Lestaurtinib), an indocarbazole derivate, is
      an FLT3 tyrosine kinase inhibitor. In this study, we investigated the effect of
      FLT3 kinase inhibition on normal hematopoietic stem and progenitor cells in
      vitro. FLT3 inhibition in normal CD34(+) cells resulted in a dose-dependent
      inhibitory effect in cell expansion. In contrast, progenitor cell function
      remained nearly unaffected. Blocking the FLT3 ligand by a neutralizing antibody
      partially restored the effects of FLT3 inhibition. These findings might explain
      hematotoxicity of tyrosine kinase inhibitors such as imatinib.

PMID- 17442780
TI  - Myocytes, myometrium, and uterine contractions.
AB  - The pregnant uterus is unique because of the dramatic functional changes that
      occur in the peripartum period. To promote the concept that we have a relatively
      poor understanding of the physiology of parturition, we will posit 10 facts that
      are so obvious and so clearly accepted as facts that they probably are not even
      facts at all. (1) The laboring uterus undergoes peristalsis to dilate the cervix,
      deliver the fetus, and expel the placenta. (2) The human uterus is composed of
      longitudinal and circular layers of smooth muscle. (3) The functional cells of
      the uterus are the myocytes, which are a homogeneous cell type responsible for
      the generation of contraction forces, passage of action potentials, and control
      of contractility. (4) The phasic contractions of the uterus are typical for
      visceral smooth muscle. (5) The primary, and perhaps only, role of gap junctions
      is to allow passage of action potentials through the tissue. (6) Action potential
      propagation as the mechanism for global communication (over many centimeters
      throughout the uterus) is sufficient to recruit all regions and all myocytes of
      the uterus. (7) Slow waves pace the contractions of human myometrium. (8) Calcium
      activated potassium channels are responsible for repolarization of the membrane
      potential that terminates each contraction. (9) Chloride channels are not
      important in uterine electrophysiology. (10) With enough computing power, it
      would be straightforward to build a closed model of human labor, given our
      current understanding of the components of myometrium. This manuscript discusses
      each point to stimulate questions for future investigation.

PMID- 17442781
TI  - Pneumonic tularemia on Martha's Vineyard: clinical, epidemiologic, and ecological
      characteristics.
AB  - Martha's Vineyard, Massachusetts, is the site of the only two recognized
      outbreaks of primary pneumonic tularemia in the United States. Beginning in 2000
      and continuing through 2006, 59 presumed or confirmed tularemia cases have been
      reported from Martha's Vineyard, with more than 60% of these presumed to be due
      to inhalation of the agent. A joint CDC/Massachusetts Department of Public Health
      case-control study identified landscaping activities such as lawnmowing or brush
      cutting to be important risk factors. The fomites that serve as the basis for
      risk for landscapers, however, remain unidentified. Clinically, cases generally
      have a pneumonic component, but the development of pulmonary signs can be greatly
      delayed. The spectrum of illness ranges from relatively mild disease, in which
      cases may be treated on an outpatient basis, to severe illness requiring
      hospitalization. In each scenario, gentamicin therapy tends to rapidly induce
      defervescence, although exceptions have been noted. Even with heightened
      awareness during the current outbreak, physicians may easily miss a diagnosis of
      tularemia, usually by attributing illness to the more common Febrile illnesses.
      Dog ticks appear to maintain the agent on this island, with as many as 5%
      infected by the agent of tularemia. The main hosts for dog ticks, skunks and
      raccoons, are very frequently seroreactive, suggesting the possibility for their
      involvement in environmental contamination due to their peridomestic habits. Why
      tularemia is prevalent on Martha's Vineyard and why it commonly presents as a
      pneumonic disease there remain undescribed.

PMID- 17442782
TI  - Expression and nephron segment-specific distribution of major renal aquaporins
      (AQP1-4) in Equus caballus, the domestic horse.
AB  - Aquaporins (AQPs) play fundamental roles in water and osmolyte homeostasis by
      facilitating water and small solute movement across plasma membranes of
      epithelial, endothelial, and other tissues. AQP proteins are abundantly expressed
      in the mammalian kidney, where they have been shown to play essential roles in
      fluid balance and urine concentration. Thus far, the majority of studies on renal
      AQPs have been carried out in laboratory rodents and sheep; no data have been
      published on the expression of AQPs in kidneys of equines or other large mammals.
      The aim of this comparative study was to determine the expression and nephron
      segment localization of AQP1-4 in Equus caballus by immunoblotting and
      immunohistochemistry with custom-designed rabbit polyclonal antisera. AQP1 was
      found in apical and basolateral membranes of the proximal convoluted tubules and
      thin descending limbs of the loop of Henle. AQP2 expression was specifically
      detected in apical membranes of cortical, medullary, and papillary collecting
      ducts. AQP3 was expressed in basolateral membranes of cortical, medullary, and
      papillary collecting ducts. Immunohistochemistry also confirmed AQP4 expression
      in basolateral membranes of cells lining the distal convoluted and connecting
      tubules. Western blots revealed high expression of AQP1-4 in the equine kidney.
      These observations confirm that AQPs are expressed in the equine kidney and are
      found in similar nephron locations to mouse, rat, and human kidney. Equine renal
      AQP proteins are likely to be involved in acute and chronic regulation of body
      fluid composition and may be implicated in water balance disorders brought about
      by colic and endotoxemia.

PMID- 17442783
TI  - Luminally released serotonin stimulates colonic motility and accelerates colonic
      transit in rats.
AB  - Enterochromaffin (EC) cells of the epithelial cells release 5-HT into the lumen,
      as well as basolateral border. However, the physiological role of released 5-HT
      into the lumen is poorly understood. Concentrations of 5-HT in the colonic
      mucosa, colonic lumen, and feces were measured by HPLC in rats. To investigate
      whether intraluminal 5-HT accelerates colonic transit, 5-HT and (51)Cr were
      administered into the lumen of the proximal colon, and colonic transit was
      measured. To investigate whether 5-HT is released into the lumen, we used an ex
      vivo model of isolated vascularly and luminally perfused rat proximal colon. To
      investigate whether luminal 5-HT is involved in regulating stress-induced colonic
      motility, the distal colonic motility was recorded under the stress loading, and
      a 5-HT(3) receptor antagonist (ondansetron, 10(-6) M, 0.5 ml) was administered
      intraluminally of the distal colon. Tissue content of 5-HT in the proximal colon
      (15.2 +/- 4.3 ng/mg wet tissue) was significantly higher than that in the distal
      colon (3.3 +/- 0.7 ng/mg wet tissue), while fecal content and luminal
      concentration of 5-HT was almost the same between the proximal and distal colon.
      Luminal administration of 5-HT (10(-6)-10(-5) M) significantly accelerated
      colonic transit. Elevation of intraluminal pressure by 10 cmH(2)O significantly
      increased the luminal concentration of 5-HT but not the vascular concentration of
      5-HT. Stress-induced stimulation of the distal colonic motility was significantly
      attenuated by the luminal administration of ondansetron. These results suggest
      that luminally released 5-HT from EC cells plays an important role in regulating
      colonic motility in rats.

PMID- 17442784
TI  - Changes in environmental temperature influence leptin responsiveness in low- and
      high-fat-fed mice.
AB  - Loss of body fat in leptin-treated animals has been attributed to reduced energy
      intake, increased thermogenesis, and preferential fatty acid oxidation. Leptin
      does not decrease food intake or body fat in leptin-resistant high-fat (HF)-fed
      mice, possibly due to a failure of leptin to activate hypothalamic receptors. We
      measured energy expenditure of male C57BL/6 mice adapted to low-fat (LF) or HF
      diet and infused them for 13 days with PBS or 10 mug leptin/day from an
      intraperitoneal mini-osmotic pump to test whether leptin resistance prevented
      leptin-induced increases in energy expenditure and fatty acid oxidation. There
      was no effect of low-dose leptin infusions on either of these measures in LF-fed
      or HF-fed mice, even though LF-fed mice lost body fat. Experiment 2 tested leptin
      responsiveness in LF-fed and HF-fed mice housed at different temperatures (18
      degrees C, 23 degrees C, 27 degrees C), assuming that the cold would increase and
      the hot environment would inhibit food intake and thermogenesis, which could
      potentially interfere with leptin action. LF-fed mice housed at 23 degrees C were
      the only mice that lost body fat during leptin infusion, suggesting that an
      ability to modify energy expenditure is essential to the maintenance of leptin
      responsiveness. HF-fed mice in cold or warm environments did not respond to
      leptin. HF-fed mice in the hot environment were fatter than other HF-fed mice,
      and, surprisingly, leptin caused a further increase in body fat, demonstrating
      that the mice were not totally leptin resistant and that partial leptin
      resistance in a hot environment favors positive energy balance and fat
      deposition.

PMID- 17442785
TI  - Effect of temperature and prolonged anoxia exposure on electrophysiological
      properties of the turtle (Trachemys scripta) heart.
AB  - Cardiac activity of the turtle (Trachemys scripta) is greatly depressed with cold
      acclimation and anoxia. We examined what electrophysiological modifications
      accompany and perhaps facilitate this depression of cardiac activity. Turtles
      were first acclimated to 21 degrees C or 5 degrees C and held under either
      normoxic or anoxic (6 h at 21 degrees C; 14 days at 5 degrees C) conditions. We
      then measured cardiac action potentials (APs) using spontaneously contracting
      whole heart preparations and whole cell current densities of sarcolemmal ion
      channels using isolated ventricular myocytes under appropriate normoxic and
      anoxic conditions. Compared with 21 degrees C-acclimated turtles, 5 degrees C
      acclimated turtles exhibited a less negative resting membrane potential (by 18-29
      mV), a 4.7- to 6.8-fold slower AP upstroke rate, and a 4.2- to 4.9-fold greater
      AP duration. Correspondingly, peak densities of ventricular voltage-gated Na(+)
      (I(Na)) and L-type Ca(2+) currents and inward slope conductances of inward
      rectifier K(+) (I(K1)) channel current were approximately 1/7th (Q(10) = 3.4),
      1/13th (Q(10) = 5.0), and one-half (Q(10) = 1.4) of those of 21 degrees C
      acclimated ventricular myocytes, respectively. With anoxia at 21 degrees C, peak
      I(Na) density doubled and ventricular AP duration increased by 47%, a change
      proportional to the reported approximately 30% reduction of intrinsic heart rate.
      In contrast, with anoxia at 5 degrees C, ventricular AP characteristics were
      unaffected; of the ion currents investigated, only the inward conductance via
      I(K1) changed significantly (reduced by 46%). The present findings indicate that
      cold temperature, more so than prolonged anoxia, results in substantial
      modifications of cardiac APs and reduction of ventricular ion current densities.
      These changes likely prepare cardiac muscle for winter anoxia conditions.

PMID- 17442786
TI  - Effect of aging on baroreflex function in humans.
AB  - Arterial blood pressure (BP) is regulated via the interaction of various local,
      humoral, and neural factors. In humans, the major neural pathway for acute BP
      regulation involves the baroreflexes. In response to baroreceptor
      activation/deactivation, as occurs during transient changes in BP, key
      determinants of BP, such as cardiac period/heart rate (via the sympathetic and
      parasympathetic nervous system) and vascular resistance (via the sympathetic
      nervous system), are modified to maintain BP homeostasis. In this review, the
      effects of aging on both the parasympathetic and sympathetic arms of the
      baroreflex are discussed. Aging is associated with decreased cardiovagal
      baroreflex sensitivity (i.e., blunted reflex changes in R-R interval in response
      to a change in BP). Mechanisms underlying this decrease may involve factors such
      as increased levels of oxidative stress, vascular stiffening, and decreased
      cardiac cholinergic responsiveness with age. Consequences of cardiovagal
      baroreflex impairment may include increased levels of BP variability, an impaired
      ability to respond to acute challenges to the maintenance of BP, and increased
      risk of sudden cardiac death. In contrast, baroreflex control of sympathetic
      outflow is not impaired with age. Collectively, changes in baroreflex function
      with age are associated with an impaired ability of the organism to buffer
      changes in BP. This is evidenced by the reduced potentiation of the pressor
      response to bolus infusion of a pressor drug after compared to before systemic
      ganglionic blockade in older compared with young adults.

PMID- 17442787
TI  - Acute regulation of the epithelial Na+ channel by phosphatidylinositide 3-OH
      kinase signaling in native collecting duct principal cells.
AB  - Activity of the epithelial Na(+) channel (ENaC) is limiting for Na(+)
      reabsorption in the aldosterone-sensitive distal nephron. Hormones, including
      aldosterone and insulin, increase ENaC activity, in part by stimulating
      phosphatidylinositide 3-OH kinase (PI3-K) signaling. Recent studies in
      heterologous expression systems reveal a close spatiotemporal coupling between
      PI3-K signaling and ENaC activity with the phospholipid product of this kinase,
      PI(3,4,5)P(3), in some cases, directly binding the channel and increasing open
      probability (P(o)). This study tested whether this tight coupling plays a
      physiologic role in modulating ENaC activity in native tissue and polarized
      epithelial cells. IGF-I was found to increase Na(+) reabsorption across
      mpkCCD(c14) principal cell monolayers in a PI3-K-sensitive manner. Inhibition of
      PI3-K signaling, moreover, rapidly decreased Na(+) reabsorption and ENaC activity
      in mpkCCD(c14) cells that were treated with corticosteroids and IGF-I. These
      decreases paralleled changes in apical membrane PI(3,4,5)P(3) levels,
      demonstrating tight spatiotemporal coupling between ENaC activity and PI3
      K/PI(3,4,5)P(3) signaling within this membrane. For further probing of the
      mechanism underpinning this coupling, cortical collecting ducts (CCD) were
      isolated from rat and split open to expose the apical membrane for patch-clamp
      analysis. Inhibition of PI3-K signaling with wortmannin and LY294002 but not its
      inactive analogue rapidly and markedly decreased the P(o) of ENaC. Moreover, IGF
      I acutely increased P(o) of ENaC in CCD principal cells in a PI3-K-sensitive
      manner. Together, these observations stress the importance of tight
      spatiotemporal coupling between PI3-K signaling and ENaC within the apical
      membrane of principal cells to the physiologic control of this ion channel.

PMID- 17442788
TI  - Normal lactational environment restores nephron endowment and prevents
      hypertension after placental restriction in the rat.
AB  - Uteroplacental insufficiency in the rat restricts fetal growth, impairs mammary
      development, compromising postnatal growth; and increases adult BP. The roles of
      prenatal and postnatal nutritional restraint on later BP and nephron endowment in
      offspring from mothers that underwent bilateral uterine vessel ligation
      (restricted) on day 18 of pregnancy were examined. Sham surgery (control) and a
      group of rats with reduced litter size (reduced; litter size reduced at birth to
      five, equivalent to restricted group) were used as controls. Offspring (control,
      reduced, and restricted) were cross-fostered on postnatal day 1 onto a control
      (normal lactation) or restricted (impaired lactation) mother. BP in male
      offspring was determined by tail cuff at 8, 12, and 20 wk of age, with glomerular
      number and volume (Cavalieri/Physical Dissector method) and renal angiotensin II
      type 1 receptor (AT(1)R) mRNA expression (real-time PCR) determined at 6 mo.
      Restricted-on-restricted male offspring developed hypertension (+16 mmHg) by 20
      wk together with a nephron deficit (-26%) and glomerular hypertrophy (P < 0.05).
      In contrast, providing a normal lactational environment to restricted offspring
      improved postnatal growth and prevented the nephron deficit and hypertension.
      Reduced-on-restricted pups that were born of normal weight but with impaired
      growth during lactation subsequently grew faster, developed hypertension (+16
      mmHg), had increased AT(1A)R and AT(1B)R mRNA expression (P < 0.05), but had no
      nephron deficit. Our study identifies the prenatal and postnatal nutritional
      environments in the programming of adult hypertension, associated with distinct
      renal changes. It is shown for the first time that a prenatally induced nephron
      deficit can be restored by correcting growth restriction during lactation.

PMID- 17442789
TI  - Exercise in the end-stage renal disease population.
AB  - Many of the known benefits of exercise in the general population are of
      particular relevance to the ESRD population. In addition, the poor physical
      functioning that is experienced by patients who are on dialysis is potentially
      addressable through exercise interventions. The study of exercise in the ESRD
      population dates back almost 30 yr, and numerous interventions, including aerobic
      training, resistance exercise training, and combined training programs, have
      reported beneficial effects. Recently, interventions during hemodialysis sessions
      have become more popular and have been shown to be safe. The risks of exercise in
      this population have not been rigorously studied, but there have been no reports
      of serious injury as a result of participation in an exercise training program.
      It is time that we incorporate exercise into the routine care of patients who are
      on dialysis, but identification of an optimal training regimen or regimens,
      according to patient characteristics or needs, is still needed to facilitate
      implementation of exercise programs.

PMID- 17442790
TI  - Myocardial ultrasound tissue characterization in patients with chronic renal
      failure.
AB  - The objective of this study was to detect ultrastructural changes in myocardium
      related to collagen content by ultrasound tissue characterization in patients
      with chronic kidney disease (CKD) and in uncomplicated hypertensive control
      subjects. In 25 hemodialysis (HD) patients, in 25 patients with moderate to
      severe chronic renal failure (CRF), and in 10 patients with essential
      hypertension (EH) and normal renal function matched for age, BP, and left
      ventricular mass index, left ventricular anatomy and function were evaluated by
      conventional echocardiography, and integrated backscatter signal (IBS) was
      analyzed by acoustic densitometry. IBS mean reflectivity increased from 48% in
      patients with EH to 56% in patients with CRF to 62% in HD patients (ANOVA P <
      0.01). IBS mean cyclic variation was progressively increased from 4.35 +/- 1.2 dB
      in HD patients to 5.27 +/- 0.90 in patients with CRF to 6.50 +/- 1.6 dB in
      patients with EH (ANOVA P < 0.01). At multivariate analysis, IBS mean
      reflectivity was positively related to age and serum creatinine (beta 0.351, P =
      0.036; and beta = 0.408, P = 0.016, respectively). IBS mean cyclic variation was
      inversely related to age and serum creatinine (beta = -0.274, P = 0.025; and beta
      = -0.262, P = 0.025, respectively) and positively related to left ventricular
      midwall fractional shortening and transmitral E/A ratio (beta = 0.269, P < 0.05;
      and beta = 0.314, P < 0.001, respectively). The data support the hypothesis that
      interstitial collagen deposition may appear early in the course of CKD and
      suggest that acoustic densitometry may represent a useful tool for the assessment
      of myocardial tissue changes in patients with CKD.

PMID- 17442791
TI  - Role of microsomal prostaglandin E synthase 1 in the kidney.
AB  - Prostaglandin E(2) (PGE(2)) is one of the most ubiquitous prostanoids in the
      kidney, where it may influence a wide range of physiologic functions. PGE(2) is
      generated through enzymatic metabolism of prostanoid endoperoxides by specific
      PGE synthases (PGES). Several putative PGES have been identified and cloned,
      including the membrane-associated, inducible microsomal PGES1 (mPGES1), which is
      expressed in the kidney. To evaluate the physiologic role of mPGES1 in the
      kidney, mice with targeted disruption of mPges1 gene were studied, with a focus
      on responses where PGE(2) has been implicated, including urinary concentration,
      regulation of blood pressure, and response to a loop diuretic. The absence of
      mPGES1 was associated with a 50% decrease in basal excretion of PGE(2) in urine
      (P < 0.001). In female but not male mPGES1-deficient mice, there was a reciprocal
      increase in basal excretion of other prostanoids. Nonetheless, urinary
      osmolalities were similar in mPges1(+/+) and mPges1(-/-) mice at baseline and
      after 12 h of water deprivation. Likewise, there were no differences in blood
      pressure between mPGES1-deficient and wild-type mice on control or high- or low
      salt diets. The furosemide-induced increase in urinary PGE(2) excretion that was
      seen in wild-type mice was attenuated in mPGES1-deficient mice. However,
      furosemide-associated diuresis was reduced only in male, not female, mPGES1
      deficient mice. Stimulation of renin by furosemide was not affected by mPGES1
      deficiency. These data suggest that mPGES1 contributes to basal synthesis of
      PGE(2), but there are other pathways that lead to renal PGE(2) synthesis.
      Moreover, there are significant gender differences in physiologic contributions
      of mPGES1 to control kidney function.

PMID- 17442792
TI  - Identification of genotypically diverse Cryptococcus neoformans and Cryptococcus
      gattii isolates by Luminex xMAP technology.
AB  - A Luminex suspension array, which had been developed for identification of
      Cryptococcus neoformans and Cryptococcus gattii isolates, was tested by
      genotyping a set of 58 mostly clinical isolates. All genotypes of C. neoformans
      and C. gattii were included. In addition, cerebrospinal fluid (CSF) obtained from
      patients with cryptococcal meningitis was used to investigate the feasibility of
      the technique for identification of the infecting strain. The suspension array
      correctly identified haploid isolates in all cases. Furthermore, hybrid isolates
      possessing two alleles of the Luminex probe region could be identified as
      hybrids. In CSF specimens, the genotype of the cryptococcal strains responsible
      for infection could be identified after optimization of the PCR conditions.
      However, further optimization of the DNA extraction protocol is needed to enhance
      the usability of the method in clinical practice.

PMID- 17442793
TI  - Multicenter laboratory evaluation of the MB/BacT Mycobacterium detection system
      and the BACTEC MGIT 960 system in comparison with the BACTEC 460TB system for
      susceptibility testing of Mycobacterium tuberculosis.
AB  - In this multicenter study, the reliability of two nonradiometric, fully automated
      systems, the MB/BacT and BACTEC MGIT 960 systems, for testing the
      susceptibilities of 82 Mycobacterium tuberculosis strains to isoniazid, rifampin,
      ethambutol, and streptomycin was evaluated in comparison with the radiometric
      BACTEC 460TB system. The arbitration of discrepant results was done by the
      reanalysis of the strain, the determination of the MIC, and the molecular
      characterization of some resistance determinants. The overall level of agreement
      with BACTEC 460TB results was 96% with the MB/BacT test and 97.2% with the BACTEC
      MGIT 960 system. With both methods, the level of agreement with BACTEC 460TB
      results was 96.3% for isoniazid, 98.8% for rifampin, and 98.8% for ethambutol.
      The level of agreement for streptomycin was 90.2% with MB/BacT and 97.5% with
      BACTEC MGIT 960. Overall, there were 11 very major errors and 2 major errors with
      the MB/BacT method and 5 very major errors and 2 major errors with the BACTEC
      MGIT 960 system. In general, the MB/BacT and BACTEC MGIT 960 systems showed good
      performance for susceptibility testing with first-line antituberculosis drugs.

PMID- 17442794
TI  - Possible transmission of Cryptosporidium canis among children and a dog in a
      household.
AB  - In a longitudinal cohort diarrhea study, a girl living in Lima, Peru, and her
      brother and dog were diagnosed with Cryptosporidium canis infections during the
      same period. Both children had transient diarrhea, but the dog was asymptomatic.
      This is the first report of possible transmission of cryptosporidiosis between
      humans and dogs.

PMID- 17442795
TI  - Performance of CAPTIA SelectSyph-G enzyme-linked immunosorbent assay in syphilis
      testing of a high-risk population: analysis of discordant results.
AB  - Using the Captia Select Syph-G enzyme-linked immunosorbent assay (ELISA), we
      analyzed the sera of 1,771 patients from a high-risk population attending
      sexually transmitted disease (STD) clinics. We focused on discrepancies between
      the results of the immunoglobulin G (IgG) ELISA and the Treponema pallidum
      hemagglutination (TPHA) test. We identified 57 patients (3.22%) with conflicting
      results in the IgG ELISA and TPHA test. In order to resolve these discrepancies,
      these patients' health records were reviewed and additional serological tests
      (rapid plasma reagin, IgM ELISA, fluorescent treponemal antibody absorption, and
      Western blotting) were performed. We subsequently diagnosed 22 of these 57
      (38.6%) patients with late latent syphilis. None of the patients with discordant
      test results was diagnosed with early syphilis. We followed 35 of these 57
      patients, analyzing two consecutive serum samples at 3 weeks and at 3 months.
      Discordant results persisted in 12 (33.3%) patients. We successfully resolved the
      test result discrepancies for 28 patients (80%) involved in follow-up. Captia
      SelectSyph-G ELISA showed a sensitivity of 99.0%, a specificity of 98.0%, and
      positive and negative predictive values of 99.3% and 97.2%, respectively. Based
      on the results of this study, we conclude that the Captia SelectSyph-G ELISA is a
      reliable tool for syphilis testing in a high-risk population and recommend the
      utilization of the Captia SelectSyph-G ELISA as a confirmatory test in at-risk
      patients.

PMID- 17442796
TI  - High-resolution genetic fingerprinting of European strains of Anaplasma
      phagocytophilum by use of multilocus variable-number tandem-repeat analysis.
AB  - Anaplasma phagocytophilum is a widely distributed tick-borne pathogen of humans,
      livestock, and companion animals. We used in silico methods to identify 10
      variable-number tandem-repeat (VNTR) loci within the genome sequence of the A.
      phagocytophilum HZ strain and used these data to develop a multilocus VNTR-based
      typing scheme for the species. Having confirmed the stability of four of the loci
      in replicates of the A. phagocytophilum strain that had been subjected to
      different numbers of passages through cell cocultures in vitro, we then used this
      typing scheme to discriminate between 20 A. phagocytophilum strains of diverse
      geographical and host provenances. Extensive diversity was found at each of the
      four loci studied, with total allele numbers ranging from 13 to 18 and Hunter
      Gaston discriminatory index values ranging from 0.93 to 0.99. Only 2 of the 20
      strains examined shared alleles at all four loci. The discriminatory power of
      VNTR analysis was found to be greater than that of either partial msp4 or 16S
      rRNA gene sequence comparison. The extremely high sensitivity of this novel
      approach to the genetic fingerprinting of A. phagocytophilum strains should serve
      well in molecular epidemiological studies of infection transmission, particularly
      when fine-scale strain delineation is required.

PMID- 17442797
TI  - Results from the ARTEMIS DISK Global Antifungal Surveillance study, 1997 to 2005:
      an 8.5-year analysis of susceptibilities of Candida species and other yeast
      species to fluconazole and voriconazole determined by CLSI standardized disk
      diffusion testing.
AB  - Fluconazole in vitro susceptibility test results for 205,329 yeasts were
      collected from 134 study sites in 40 countries from June 1997 through December
      2005. Data were collected for 147,776 yeast isolates tested with voriconazole
      from 2001 through 2005. All investigators tested clinical yeast isolates by the
      CLSI M44-A disk diffusion method. Test plates were automatically read and results
      recorded with a BIOMIC image analysis system. Species, drug, zone diameter,
      susceptibility category, and quality control results were collected quarterly.
      Duplicate (same patient, same species, and same susceptible-resistant biotype
      profile during any 7-day period) and uncontrolled test results were not analyzed.
      Overall, 90.1% of all Candida isolates tested were susceptible (S) to
      fluconazole; however, 10 of the 22 species identified exhibited decreased
      susceptibility (<75% S) on the order of that seen with the resistant (R) species
      C. glabrata and C. krusei. Among 137,487 isolates of Candida spp. tested against
      voriconazole, 94.8% were S and 3.1% were R. Less than 30% of fluconazole
      resistant isolates of C. albicans, C. glabrata, C. tropicalis, and C. rugosa
      remained S to voriconazole. The non-Candida yeasts (8,821 isolates) were
      generally less susceptible to fluconazole than Candida spp. but, aside from
      Rhodotorula spp., remained susceptible to voriconazole. This survey demonstrates
      the broad spectrum of these azoles against the most common opportunistic yeast
      pathogens but identifies several less common yeast species with decreased
      susceptibility to antifungal agents. These organisms may pose a future threat to
      optimal antifungal therapy and emphasize the importance of prompt and accurate
      species identification.

PMID- 17442798
TI  - Genetic and antigenic analysis of invasive serogroup Y Neisseria meningitidis
      isolates collected from 1999 to 2003 in Canada.
AB  - One hundred forty serogroup Y Neisseria meningitidis isolates recovered from
      patients with invasive meningococcal disease (IMD) in Canada from 1999 to 2003
      were analyzed by genetic and serological methods. Seventy-four isolates (52.9%)
      belonged to serotype 2c, and most have serosubtype antigen P1.5,2 (37 isolates,
      26%) or P1.5 (31 isolates, 22%). Forty-eight isolates (34.3%) belonged to
      serotype 14 and have serosubtype antigen P1.5,2 (13 isolates, 9%) or P1.5 (7
      isolates, 5%) or were nonserosubtypeable (27 isolates, 19%). Thirteen isolates
      (9.3%) were nonserotypeable. Multilocus sequence typing identified two unrelated
      clonal populations of serogroup Y meningococci causing invasive disease in
      Canada: ST-23 and ST-167 clonal complexes. Almost all ST-167-related isolates
      were typed as 2c:P1.5, while strains of the ST-23 clonal complex were either
      serotype 14 or 2c but with the serosubtype antigen P1.5,2. In contrast to
      previous reports that patients with serogroup Y disease are usually older, 26% of
      the Canadian serogroup Y cases were found in the 10-to-19-year-old age group and
      another 11% were in the 20-to-39-year-old age group.

PMID- 17442799
TI  - Both human immunodeficiency virus cellular DNA sequencing and plasma RNA
      sequencing are useful for detection of drug resistance mutations in blood samples
      from antiretroviral-drug-naive patients.
AB  - Genotypic antiretroviral testing is recommended for newly infected drug-naive
      subjects, and the material of choice is plasma RNA. Since drug resistance
      mutations (DRMs) may persist longer in cellular DNA than in plasma RNA, we
      investigated whether the use of peripheral blood mononuclear cell (PBMC) human
      immunodeficiency virus (HIV) DNA increases the sensitivity of genotypic testing
      in antiretroviral-drug-naive subjects. We compared the rate of primary drug
      resistance in plasma RNA and PBMC DNA in 288 HIV type 1-infected drug-naive
      persons tested at a single clinical virology center from June 2004 to October
      2006. Resistance in the plasma compartment to at least one drug was detected for
      64 out of 288 (22.2%) naive patients and in the PBMC compartment for 56 (19.4%)
      patients. Overall, DRMs were found in 80 out of 288 (27.8%) patients. PBMC DNA
      [corrected] DRMs were present in [corrected] 16 subjects with wild-type virus in
      their plasma RNA [corrected] Another nine patients had additional DRMs in their
      PBMC DNA [corrected] with respect to those detected in their [corrected] plasma
      RNA. On the other hand, extra plasma RNA [corrected] DRMs were detected in
      [corrected] 24 and 8 subjects with wild-type and drug-resistant virus in their
      PBMC DNA [corrected] respectively. Resistance to more than one class of
      antiretroviral drug was detected by plasma and PBMC analysis for 25.0% and 36.2%
      of the subjects, respectively. Our data support the potential utility of
      genotypic resistance testing of PBMC DNA in conjunction with the currently
      recommended plasma RNA analysis.

PMID- 17442800
TI  - Molecular discrimination of atypical bovine spongiform encephalopathy strains
      from a geographical region spanning a wide area in Europe.
AB  - Transmissible spongiform encephalopathy strains can be differentiated by their
      behavior in bioassays and by molecular analyses of the disease-associated prion
      protein (PrP) in a posttranslationally transformed conformation (PrPSc). Until
      recently, isolates from cases of bovine spongiform encephalopathy (BSE) appeared
      to be very homogeneous. However, a limited number of atypical BSE isolates have
      recently been identified upon analyses of the disease-associated proteinase K
      (PK) resistance-associated moiety of PrPSc (PrPres), suggesting the existence of
      at least two additional BSE PrPres variants. These are defined here as the H type
      and the L type, according to the higher and lower positions of the
      nonglycosylated PrPres band in Western blots, respectively, compared to the
      position of the band in classical BSE (C-type) isolates. These molecular PrPres
      variants, which originated from six different European countries, were
      investigated together. In addition to the migration properties and glycosylation
      profiles (glycoprofiles), the H- and L-type isolates exhibited enhanced PK
      sensitivities at pH 8 compared to those of the C-type isolates. Moreover, H-type
      BSE isolates exhibited differences in the binding of antibodies specific for N-
      and more C-terminal PrP regions and principally contained two aglycosylated
      PrPres moieties which can both be glycosylated and which is thus indicative of
      the existence of two PrPres populations or intermediate cleavage sites. These
      properties appear to be consistent within each BSE type and independent of the
      geographical origin, suggesting the existence of different BSE strains in cattle.
      The choice of three antibodies and the application of two pHs during the
      digestion of brain homogenates provide practical and diverse tools for the
      discriminative detection of these three molecular BSE types and might assist with
      the recognition of other variants.

PMID- 17442801
TI  - Fatal echovirus 18 leukoencephalitis in a child.
AB  - Rare cases of leukoencephalitis have been reported in infants with documented
      enterovirus (EV) central nervous system (CNS) infections. A case of fatal
      encephalitis with white matter lesions caused by echovirus 18 is described, and
      it highlights the role of EV CNS infection as a potential cause of
      leukoencephalitis in infants.

PMID- 17442802
TI  - Multilocus genotyping identifies infections by multiple strains of Trichophyton
      tonsurans.
AB  - Acquisition of multiple genetic strains of a single dermatophyte species should
      not be unexpected in areas of high endemicity, and yet multistrain infections are
      infrequently reported. This communication details mixed Trichophyton tonsurans
      infections and highlights the need to confirm the presence of multiple strains in
      a clinical single isolate by use of a multilocus approach.

PMID- 17442803
TI  - Pantoea agglomerans, a plant pathogen causing human disease.
AB  - We present 53 pediatric cases of Pantoea agglomerans infections cultured from
      normally sterile sites in patients seen at a children's hospital over 6 years.
      Isolates included 23 from the bloodstream, 14 from abscesses, 10 from
      joints/bones, 4 from the urinary tract, and 1 each from the peritoneum and the
      thorax. P. agglomerans was most associated with penetrating trauma by vegetative
      material and catheter-related bacteremia.

PMID- 17442804
TI  - Development of a serological assay based on a synthetic peptide selected from the
      VP0 capsid protein for detection of human parechoviruses.
AB  - A serological enzyme-linked immunosorbent assay was developed using a synthetic
      peptide from the VP0 protein of human parechoviruses (HPeVs). Seroprevalence for
      HPeVs was 70% in children of < or = 5 years of age and 95% in adults. For
      children from whom serial sera were sampled, seropositivity increased from 22% to
      88% between 2 and 24 months of age.

PMID- 17442805
TI  - Molecular epidemiology and clinical manifestations of viral gastroenteritis in
      hospitalized pediatric patients in Northern Taiwan.
AB  - By reverse transcription-PCR or PCR, among 257 children with nonbacterial acute
      gastroenteritis (AGE), rotavirus, norovirus, astrovirus, enteric adenovirus, and
      multiple viruses were identified in 78 (30.4%), 21 (8.2%), 7 (2.7%), 51 (19.8%),
      and 53 (20.6%) patients, respectively. Higher disease severity was found for AGE
      caused by multiple viruses and by rotavirus alone. The majority of rotaviruses
      isolated from 2004 to 2006 belonged to genotypes G1 (20.4%), G2 (16.5%), G3
      (27.2%), and G9 (21.4%).

PMID- 17442806
TI  - Synaptotagmin: is 2 better than 1?

PMID- 17442807
TI  - The proneural gene Mash1 specifies an early population of telencephalic
      oligodendrocytes.
AB  - The bHLH (basic helix-loop-helix) transcription factor Mash1 is best known for
      its role in the regulation of neurogenesis. However, Mash1 is also expressed in
      oligodendrocyte precursors and has recently been shown to promote the generation
      of oligodendrocytes in cell culture, suggesting that it may regulate
      oligodendrogenesis as well. Here, we show that in the developing ventral
      forebrain, Mash1 is expressed by a subset of oligodendrocyte precursors (OPCs) as
      soon as they are generated in the ventricular zone. Using reporter mice, we
      demonstrate that a subset of OPCs in both the embryonic and postnatal forebrain
      originate from Mash1-positive progenitors, including a large fraction of adult
      NG2-positive OPCs. Using Mash1 null mutant mice, we show that Mash1 is required
      for the generation of an early population of OPCs in the ventral forebrain
      between embryonic day 11.5 (E11.5) and E13.5, whereas OPCs generated later in
      embryonic development are not affected. Overexpression of Mash1 in the dorsal
      telencephalon induces expression of PDGFRalpha (platelet-derived growth factor
      receptor alpha) but not other OPC markers, suggesting that Mash1 specifies
      oligodendrogenesis in cooperation with other factors. Analysis of double-mutant
      mice suggests that Olig2 is one of the factors that cooperate with Mash1 for
      generation of OPCs. Together, our results show for the first time that Mash1
      cooperates in vivo with Olig2 in oligodendrocyte specification, demonstrating an
      essential role for Mash1 in the generation of a subset of oligodendrocytes and
      revealing a genetic heterogeneity of oligodendrocyte lineages in the mouse
      forebrain.

PMID- 17442808
TI  - Processing of Reelin by embryonic neurons is important for function in tissue but
      not in dissociated cultured neurons.
AB  - Reelin, the protein defective in reeler mutant mice, plays a key role during
      brain development. Reelin is processed proteolytically at two sites, and the
      central fragment mimics function in vitro. Here, we show that processing is
      functionally important in vivo, a question that could not be addressed in our
      previous study. New monoclonal antibodies directed against central Reelin block
      its binding to lipoprotein receptors and perturb cortical development in vitro,
      confirming the importance of the central fragment that is detected in tissue and
      body fluids. Processing occurs when Reelin is incubated with embryonic neurons in
      culture or with their supernatant, but inhibition of processing by a
      metalloproteinase blocker does not prevent Reelin signaling in neurons.
      Furthermore, neurons internalize similarly full-length or central Reelin. In
      contrast, inhibition of processing prevents signaling and perturbs cortical
      development in cultured embryonic brain slices. Moreover, in vivo, the
      concentration of central Reelin is dramatically and selectively increased in
      receptor-deficient tissue, suggesting its specific downregulation after binding
      to receptors and internalization. We propose that processing by end-migration
      neurons is required in tissue (where Reelin is likely anchored to the
      extracellular matrix) to release the central fragment that diffuses locally and
      signals to target cells, whereas, in vitro, all Reelin forms have indiscriminate
      access to cells, so that cleavage is not necessary for signaling.

PMID- 17442810
TI  - Thalamocortical Up states: differential effects of intrinsic and extrinsic
      cortical inputs on persistent activity.
AB  - During behavioral quiescence, the neocortex generates spontaneous slow
      oscillations that consist of Up and Down states. Up states are short epochs of
      persistent activity that resemble the activated neocortex during arousal and
      cognition. Although Up states are generated within the cortex, the impact of
      extrinsic (thalamocortical) and intrinsic (intracortical) inputs on the
      persistent activity is not known. Using thalamocortical slices, we found that the
      persistent cortical activity during spontaneous Up states effectively drives
      thalamocortical relay cells through corticothalamic connections. However,
      thalamic activity can also precede the onset of cortical Up states, which
      suggests a role of thalamic activity in triggering cortical Up states through
      thalamocortical connections. In support of this hypothesis, we found that cutting
      the connections between thalamus and cortex reduced the incidence of spontaneous
      Up states in the cortex. Consistent with a facilitating role of thalamic activity
      on Up states, electrical or chemical stimulation of the thalamus triggered
      cortical Up states very effectively and enhanced those occurring spontaneously.
      In contrast, stimulation of the cortex triggered Up states only at very low
      intensities but otherwise had a suppressive effect on Up states. Moreover,
      cortical stimulation suppressed the facilitating effect of thalamic stimulation
      on Up states. In conclusion, thalamocortical inputs facilitate and intracortical
      inputs suppress cortical Up states. Thus, extrinsic and intrinsic cortical inputs
      differentially regulate persistent activity, which may serve to adjust the
      processing state of thalamocortical networks during behavior.

PMID- 17442809
TI  - Selective dysfunction of hippocampal CA1 astrocytes contributes to delayed
      neuronal damage after transient forebrain ischemia.
AB  - Transient global ischemia, as with cardiac arrest, causes loss of CA1 hippocampal
      neurons 2-4 d later, whereas nearby dentate gyrus (DG) neurons are relatively
      resistant. Whether differential astrocyte vulnerability in ischemic injury
      contributes to CA1 neuronal death is uncertain. Here, we find that CA1 astrocytes
      are more sensitive to ischemia than DG astrocytes. In rats subjected to transient
      forebrain ischemia, CA1 astrocytes lose glutamate transport activity and
      immunoreactivity for GFAP, S100beta, and glutamate transporter GLT-1 within a few
      hours of reperfusion, but without astrocyte cell death. Oxidative stress may
      contribute to the observed selective CA1 changes, because CA1 astrocytes show
      early increases in mitochondrial free radicals and reduced mitochondrial membrane
      potential. Similar changes were not observed in DG astrocytes. Upregulation of
      GLT-1 expression in astrocytes with ceftriaxone protected CA1 neurons from
      forebrain ischemia. We suggest that greater oxidative stress and loss of GLT-1
      function selectively in CA1 astrocytes is central to the well known delayed death
      of CA1 neurons.

PMID- 17442811
TI  - Changes in Sef levels influence auditory brainstem development and function.
AB  - During development of the CNS, secreted morphogens of the fibroblast growth
      factor (FGF) family have multiple effects on cell division, migration, and
      survival depending on where, when, and how much FGF signal is received. The
      consequences of misregulating the FGF pathway were studied in a mouse with
      decreased levels of the FGF antagonist Sef. To uncover effects in the nervous
      system, we focused on the auditory system, which is accessible to physiological
      analysis. We found that the mitogen-activated protein kinase pathway is active in
      the rhombic lip, a germinal zone that generates diverse types of neurons,
      including the cochlear nucleus complex of the auditory system. Sef is expressed
      immediately adjacent to the rhombic lip, overlapping with FGF15 and FGFR1, which
      is also present in the lip itself. This pattern suggests that Sef may normally
      function in non-rhombic lip cells and prevent them from responding to FGF ligand
      in the vicinity. Consistent with this idea, overexpression of Sef in chicks
      decreased the size of the auditory nuclei. Cochlear nucleus defects were also
      apparent in mice with reduced levels of Sef, with 13% exhibiting grossly
      dysmorphic cochlear nuclei and 26% showing decreased amounts of GFAP in the
      cochlear nucleus. Additional evidence for cochlear nucleus defects was obtained
      by electrophysiological analysis of Sef mutant mice, which have normal auditory
      thresholds but abnormal auditory brainstem responses. These results show both
      increases and decreases in Sef levels affect the assembly and function of the
      auditory brainstem.

PMID- 17442812
TI  - Differential intrinsic response dynamics determine synaptic signal processing in
      frog vestibular neurons.
AB  - Central vestibular neurons process head movement-related sensory signals over a
      wide dynamic range. In the isolated frog whole brain, second-order vestibular
      neurons were identified by monosynaptic responses after electrical stimulation of
      individual semicircular canal nerve branches. Neurons were classified as tonic or
      phasic vestibular neurons based on their different discharge patterns in response
      to positive current steps. With increasing frequency of sinusoidally modulated
      current injections, up to 100 Hz, there was a concomitant decrease in the
      impedance of tonic vestibular neurons. Subthreshold responses as well as spike
      discharge showed classical low-pass filter-like characteristics with corner
      frequencies ranging from 5 to 20 Hz. In contrast, the impedance of phasic
      vestibular neurons was relatively constant over a wider range of frequencies or
      showed a resonance at approximately 40 Hz. Above spike threshold, single spikes
      of phasic neurons were synchronized with the sinusoidal stimulation between
      approximately 20 and 50 Hz, thus showing characteristic bandpass filter-like
      properties. Both the subthreshold resonance and bandpass filter-like discharge
      pattern depend on the activation of an I(D) potassium conductance. External
      current or synaptic stimulation that produced impedance increases (i.e.,
      depolarization in tonic or hyperpolarization in phasic neurons) had opposite and
      complementary effects on the responses of the two types of neurons. Thus,
      membrane depolarization by current steps or repetitive synaptic excitation
      amplified synaptic inputs in tonic vestibular neurons and reduced them in phasic
      neurons. These differential, opposite membrane response properties render the two
      neuronal types particularly suitable for either integration (tonic neurons) or
      signal detection (phasic neurons), respectively, and dampens variations of the
      resting membrane potential in the latter.

PMID- 17442813
TI  - Dorsal radial glia generate olfactory bulb interneurons in the postnatal murine
      brain.
AB  - During embryogenesis, dorsal radial glia generate pyramidal cell neurons but not
      interneurons, and are thought to degenerate or transform into astrocytes in the
      postnatal brain. Ventral radial glia, in contrast, retract their processes to
      form GFAP+ subventricular zone (SVZ) astrocytes that continue to generate
      interneurons into adulthood. We sought to fate map dorsal radial glia by
      codelivering an adenovirus expressing Cre recombinase and a lentivirus expressing
      dsRedExpress to the dorsal cortical surface of ROSA26R-YFP mice. Whereas the
      adenovirus is retrogradely transported to the cell body, the VSV-G (vesicular
      stomatitis virus G) pseudotyped lentivirus is not and allows us to control for
      viral diffusion from the site of infection. We found that dorsal radial glia give
      rise to gray and white matter astrocytes and oligodendrocytes. In addition, the
      dorsal radial glia fate map to astrocytes lining the dorsal aspect of the SVZ
      that persist at least 8 weeks postnatally. Finally, we found that dorsal radial
      glial-derived cells generate granule cell and periglomerular interneurons in the
      olfactory bulb and continue to form interneuronal precursors into adulthood.

PMID- 17442814
TI  - Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury.
AB  - Prostaglandin D2 (PGD) is synthesized by hematopoietic PGD synthase (HPGDS) or
      lipocalin-type PGDS (L-PGDS), depending on the organ in which it is produced, and
      binds specifically to either DP1 or DP2 receptors. We investigated the role of
      PGD2 in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonatal
      mice at postnatal day 7. In wild-type mice, hypoxia-ischemia increased PGD2
      production in the brain up to 90-fold compared with the level in sham-operated
      brains at 10 min after cessation of hypoxia. Whereas the size of the infarct was
      not changed in L-PGDS or DP2 knock-out mouse brains compared with that in the
      wild-type HIE brains, it was significantly increased in HPGDS-L-PGDS double knock
      out or DP1 knock-out mice. The PGD2 level in L-PGDS, HPGDS, and HPGDS-L-PGDS
      knock-out mice at 10 min of reoxygenation was 46, 7, and 1%, respectively, of
      that in the wild-type ones, indicating the infarct size to be in inverse relation
      to the amount of PGD2 production. DP1 receptors were exclusively expressed in
      endothelial cells after 1 h of reoxygenation, and cerebral blood flow decreased
      more rapidly after the onset of hypoxia and did not return to the baseline level
      after reoxygenation in HPGDS-L-PGDS knock-out mice. Endothelial cells were
      severely damaged in HPGDS-L-PGDS and DP1 knock-out mice after 1 h of
      reoxygenation. In the human neonatal HIE brain, HPGDS-positive microglia were
      increased in number. In conclusion, it is probable that PGD2 protected the
      neonatal brain from hypoxic-ischemic injury mainly via DP1 receptors by
      preventing endothelial cell degeneration.

PMID- 17442815
TI  - Shape change controls supporting cell proliferation in lesioned mammalian balance
      epithelium.
AB  - Mature mammals are uniquely vulnerable to permanent auditory and vestibular
      deficits, because the cell proliferation that produces replacement hair cells in
      other vertebrates is limited in mammals. To investigate the cellular mechanisms
      responsible for that difference, we created excision lesions in the sensory
      epithelium of embryonic and 2-week-old mouse utricles. Lesions in embryonic
      utricles closed in <24 h via localized expansion of supporting cells, which then
      reentered the cell cycle. Pharmacological treatments combined with time-lapse
      microscopy demonstrated that the healing depended on Rho-mediated contraction of
      an actin ring at the leading edge of the lesion. In contrast, lesions in utricles
      from 2-week-old and older mice remained open even after 48 h. Supporting cells in
      those utricles remained compact and columnar and had significantly stouter
      cortical actin belts than those in embryonic sensory epithelia. This suggests
      that cytoskeletal changes may underlie the age-related loss of proliferation in
      mammalian ears by limiting the capacity for mature supporting cells to change
      shape. In mature utricles, exogenous stimulation with lysophosphatidic acid
      overcame this maturational block and induced closure of lesions, promoting
      supporting cell expansion and subsequent proliferation. After lysophosphatidic
      acid treatment, 85% of the mature supporting cells that had spread to a planar
      area >300 microm2 entered S-phase, whereas only 10% of those cells that had a
      planar area <100 microm2 entered S-phase. Together, these results indicate that
      cellular shape change can overcome the normal postnatal cessation of supporting
      cell proliferation that appears to limit regeneration in mammalian vestibular
      epithelia.

PMID- 17442816
TI  - An orally active catalytic metalloporphyrin protects against 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine neurotoxicity in vivo.
AB  - Parkinson's disease (PD) is an age-related neurodegenerative disease in which the
      role of reactive oxygen species (ROS) is strongly implicated. The presence of
      oxidative stress has been detected in human and experimental PD using both direct
      and indirect indices. Scavenging ROS is, therefore, an important therapeutic
      avenue for the treatment of PD. Manganic porphyrins are catalytic antioxidants
      that scavenge a wide range of ROS. In this study, we tested the therapeutic
      effects of a compound [5,15-bis(methoxycarbonyl)-10,20-bis-trifluoromethyl
      porphyrinato manganese (III) chloride (AEOL11207)] belonging to a new generation
      of lipophilic manganic porphyrins for neuroprotection and oral bioavailability in
      the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of
      parkinsonism. Groups of adult C57BL/6 mice were administered MPTP with varying
      subcutaneous or oral dosing regimens of AEOL11207. Neurotoxicity was assessed by
      measurement of striatal dopamine levels and quantification of tyrosine
      hydroxylase-positive neurons in the substantial nigra pars compacta one week
      after the first dose of MPTP. Glutathione depletion, lipid peroxidation, and 3
      nitrotyrosine (3-NT) formation were measured as indicators of oxidative stress in
      the ventral midbrain in vivo. AEOL11207 administered either by subcutaneous or
      oral routes protected against MPTP-induced dopamine depletion in the striatum as
      well as dopaminergic neuronal loss, glutathione depletion, lipid peroxidation,
      and 3-NT formation in the ventral midbrain. Neuroprotection correlated with brain
      metalloporphyrin concentrations. This is the first demonstration of
      neuroprotection by an orally active catalytic antioxidant in the MPTP mouse model
      and suggests its potential clinical utility for the treatment of chronic
      neurodegenerative diseases such as PD.

PMID- 17442817
TI  - How do primates anticipate uncertain future events?
AB  - The timing of an upcoming event depends on two factors: its temporal position,
      proximal or distal with respect to the present moment, and the unavoidable
      stochastic variability around this temporal position. We searched for a general
      mechanism that could describe how these two factors influence the anticipation of
      an upcoming event in an oculomotor task. Monkeys were trained to pursue a moving
      target with their eyes. During a delay period inserted before target motion
      onset, anticipatory pursuit responses were frequently observed. We found that
      anticipatory movements were altered by the temporal position of the target.
      Increasing the timing uncertainty associated with the stimulus resulted in an
      increase in the width of the latency distribution of anticipatory pursuit. These
      results show that monkeys relied on an estimation of the changing probability of
      target motion onset as time elapsed during the delay to decide when to initiate
      an anticipatory smooth eye movement.

PMID- 17442818
TI  - Netrin-1/DCC signaling in commissural axon guidance requires cell-autonomous
      expression of heparan sulfate.
AB  - There is increasing evidence that heparan sulfate (HS) plays an essential role in
      various axon guidance processes. These observations, however, have not addressed
      whether HS is required cell autonomously as an axonal coreceptor or as an
      environmental factor that modulates the localization of guidance molecules in the
      terrain in which growing axons navigate. Here we demonstrate that netrin-1
      mediated commissural axon guidance requires cell-autonomous expression of HS in
      commissural neurons in vivo. We used the Wnt1-Cre transgene to drive region
      specific ablation of Ext1, which encodes an enzyme essential for HS synthesis, in
      the dorsal part of the spinal cord. Remarkably, Wnt1-Cre-mediated ablation of
      Ext1 causes commissural axon pathfinding defects that share similarities with
      those of Netrin-1-deficient and DCC (deleted in colorectal cancer)-deficient
      mice. Neither Ext1-deficient dorsal spinal cord explants nor wild-type explants
      in which HS expression was ablated could extend axons in response to netrin-1.
      Intracellular signaling downstream of netrin-1 and DCC was defective in Ext1
      deficient commissural neurons and in DCC-transfected HEK293T cells from which HS
      was removed. These results demonstrate that the expression of HS by commissural
      neurons is essential for these neurons to transduce netrin-1 signals, thus
      providing evidence for a cell-autonomous role of HS in netrin-1/DCC-mediated axon
      guidance.

PMID- 17442819
TI  - Entrainment to feeding but not to light: circadian phenotype of VPAC2 receptor
      null mice.
AB  - The master clock driving mammalian circadian rhythms is located in the
      suprachiasmatic nuclei (SCN) of the hypothalamus and entrained by daily
      light/dark cycles. SCN lesions abolish circadian rhythms of behavior and result
      in a loss of synchronized circadian rhythms of clock gene expression in
      peripheral organs (e.g., the liver) and of hormone secretion (e.g.,
      corticosterone). We examined rhythms of behavior, hepatic clock gene expression,
      and corticosterone secretion in VPAC2 receptor-null (Vipr2-/-) mice, which lack a
      functional SCN clock. Unexpectedly, although Vipr2-/- mice lacked robust
      circadian rhythms of wheel-running activity and corticosterone secretion, hepatic
      clock gene expression was strongly rhythmic, but advanced in phase compared with
      that in wild-type mice. The timing of food availability is thought to be an
      important entrainment signal for circadian clocks outside the SCN. Vipr2-/- mice
      consumed food significantly earlier in the 24 h cycle than wild-type mice,
      consistent with the observed timing of peripheral rhythms of circadian gene
      expression. When restricted to feeding only during the daytime (RF), mice develop
      rhythms of activity and of corticosterone secretion in anticipation of feeding
      time, thought to be driven by a food-entrainable circadian oscillator, located
      outside the SCN. Under RF, mice of both genotypes developed food-anticipatory
      rhythms of activity and corticosterone secretion, and hepatic gene expression
      rhythms also became synchronized to the RF stimulus. Thus, food intake is an
      effective zeitgeber capable of coordinating circadian rhythms of behavior,
      peripheral clock gene expression, and hormone secretion, even in the absence of a
      functional SCN clock.

PMID- 17442820
TI  - Vagal regulation of respiratory clocks in mice.
AB  - The present study addresses the role of the circadian system in day-night changes
      of respiratory functions in the mouse. In all airway tissues investigated (i.e.,
      larynx, trachea, bronchus, and lung), we observed clear rhythmic expression of
      the Per1, Per2, Bmal1, and Clock core oscillator genes (the latter two genes
      oscillating in antiphase with the Per genes), as well as the clock-regulated Dbp
      gene. Oscillations were abolished in arrhythmic Cry1-/- Cry2-/- knock-out mice
      and after lesioning of the master clock in the suprachiasmatic nucleus (SCN) in
      wild-type animals. These findings indicate that respiratory system cells contain
      a functional peripheral oscillator that is controlled by the SCN. Furthermore, we
      found that the muscarinic acetylcholine receptor genes Chm2, Chm3, and Chm4 are
      expressed in a circadian manner, and that mucin secretion (rather than synthesis)
      by the airway submucosal glands is under circadian control. Signals from the SCN
      are mainly transmitted by the vagal nerve because unilateral vagotomy completely
      abolished rhythms in mucin and PER2 protein levels in the (operated) ipsilateral
      side of the submucosal glands, but not in the (intact) contralateral side. Thus,
      peripheral clock mediated circadian expression of muscarinic acetylcholine
      receptor proteins, and parasympathetic signaling between SCN and respiratory
      tissues are essential gears in conferring circadian "time" information to airway
      glands.

PMID- 17442821
TI  - Independent effects of emotion and working memory load on visual activation in
      the lateral occipital complex.
AB  - Emotional salience and working memory (WM) load are known to affect object
      processing in the ventral stream. However, the combined effect, which could be
      either synergistic or antagonistic, remains unclear. Using functional magnetic
      resonance imaging and a three-factorial design, we investigated the effects of WM
      load and emotional salience on object processing in the ventral visual stream.
      Twenty-three female subjects were shown blocks of task-irrelevant and more or
      less degraded visual stimuli that varied in emotional valence (negative or
      neutral) and phase coherence rendering them more or less noisy. Superimposed on
      these pictures, subjects saw colored squares on which they had to perform a
      demanding WM task (one-back, two-back). This WM task absorbs attentional
      resources normally available for the perceptual analysis of visual objects and
      can therefore be interpreted as a manipulation of attention. We hypothesized that
      attenuated processing resources in the lateral occipital complex (LOC) for these
      task-irrelevant pictures under high WM load (Rose et al., 2005) could be regained
      when they were of negative emotional valence. Our results indicate that both
      emotional salience and WM load critically depend on a minimum level of phase
      coherence of the stimuli to affect LOC activation. Furthermore, the influences of
      emotional salience and WM load do not interact with each other in LOC. Rather,
      emotional salience exerts a general multiplicative gain effect while preserving
      the difference in activation between low and high WM load. A connectivity
      analysis suggests that the emotional modulation might originate in the amygdalo
      hippocampal junction.

PMID- 17442822
TI  - Novel and distinct operational principles of intralaminar thalamic neurons and
      their striatal projections.
AB  - Neurons of the intralaminar thalamus, including central lateral (CL) and
      parafascicular (Pf) nuclei, innervate the cortex and striatum and are important
      for cognitive, sensory, and motor processes. We tested the hypothesis that CL and
      Pf neurons provide functionally distinct inputs to the striatum. We performed
      recordings of single CL and Pf neurons in anesthetized rats and, after
      juxtacellularly labeling the neurons, their somatodendritic features and synaptic
      connections were characterized. All CL neurons (n = 31) discharged classic low
      threshold Ca2+ spike bursts during cortical slow-wave activity in vivo. In
      contrast, Pf neurons (n = 52) rarely fired such bursts, but instead discharged
      groups of spikes at relatively low frequencies. The activity of CL and Pf neurons
      was often temporally coupled to cortical slow oscillations. Identified CL neurons
      possessed archetypal "bushy" dendrites and preferentially established synapses
      with dendritic spines (91% of synapses) of striatal projection neurons. Pf
      neurons possessed "reticular-like" dendrites, and, on average, preferentially
      established synapses with dendritic shafts (63%) in striatum, although
      connectivity was markedly heterogeneous across neurons. Two of the six Pf neurons
      studied exclusively targeted dendritic shafts, whereas another neuron almost
      exclusively (97%) targeted spines. The remaining three neurons preferentially
      targeted dendritic shafts (53-70%). Thus, the fundamental properties of CL and Pf
      neurons differ (the latter do not express the typical operational principles of
      thalamic relay neurons), and they provide different temporally patterned inputs
      to distinct striatal targets. This mechanistic diversity likely underpins the
      transmission of specific and discrete information from intralaminar thalamic
      nuclei to striatal and cortical targets.

PMID- 17442823
TI  - Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-beta
      and tau pathology via a mechanism involving presenilin 1 levels.
AB  - The underlying cause of sporadic Alzheimer disease (AD) is unknown, but a number
      of environmental and genetic factors are likely to be involved. One environmental
      factor that is increasingly being recognized as contributing to brain aging is
      diet, which has evolved markedly over modern history. Here we show that dietary
      supplementation with docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty
      acid, in the 3xTg-AD mouse model of AD reduced the intraneuronal accumulation of
      both amyloid-beta (Abeta) and tau. In contrast, combining DHA with n-6 fatty
      acids, either arachidonic acid or docosapentaenoic acid (DPAn-6), diminished the
      efficacy of DHA over a 12 month period. Here we report the novel finding that the
      mechanism accounting for the reduction in soluble Abeta was attributable to a
      decrease in steady-state levels of presenilin 1, and not to altered processing of
      the amyloid precursor protein by either the alpha- or beta-secretase.
      Furthermore, the presence of DPAn-6 in the diet reduced levels of early-stage
      phospho-tau epitopes, which correlated with a reduction in phosphorylated c-Jun N
      terminal kinase, a putative tau kinase. Collectively, these results suggest that
      DHA and DPAn-6 supplementations could be a beneficial natural therapy for AD.

PMID- 17442825
TI  - Systemic inflammatory stimulus potentiates the acute phase and CXC chemokine
      responses to experimental stroke and exacerbates brain damage via interleukin-1-
      and neutrophil-dependent mechanisms.
AB  - Systemic inflammatory stimuli, such as infection, increase the risk of stroke and
      are associated with poorer clinical outcome. The mechanisms underlying the impact
      of systemic inflammatory stimuli on stroke are not well defined. We investigated
      the impact of systemic inflammation on experimental stroke and potential
      mechanisms involved. Focal cerebral ischemia was induced by intraluminal filament
      occlusion of the middle cerebral artery (MCAo). Brain damage and neurological
      deficit 24 h after MCAo were exacerbated by systemic lipopolysaccharide (LPS)
      administration. This exacerbation was critically dependent on interleukin (IL)-1,
      because coadministration of IL-1 receptor antagonist abolished the effect of LPS
      on brain damage. Systemic administration of IL-1 increased ischemic damage to a
      similar extent as LPS and also exacerbated brain edema. IL-1 markedly potentiated
      circulating levels of the acute phase proteins, serum amyloid A and IL-6, and the
      neutrophil-selective CXC chemokines, KC and macrophage inflammatory protein-2.
      Neutrophil mobilization and cortical neutrophil infiltration were aggravated by
      IL-1 before changes in ischemic damage. Neutropenia abolished the damaging
      effects of systemic IL-1. These data show for the first time that an acute
      systemic inflammatory stimulus is detrimental to outcome after experimental
      stroke and highlight IL-1 as a critical mediator in this paradigm. Our data
      suggest IL-1-induced potentiation of neutrophil mobilization via CXC chemokine
      induction is a putative mechanism underlying this effect. Our results may help to
      explain the poorer outcome in stroke patients presenting with infection and may
      have implications for neurodegenerative diseases involving neurovascular
      alterations, such as Alzheimer's disease, in which systemic inflammation can
      modulate disease progression.

PMID- 17442824
TI  - Receptor-like tyrosine phosphatase PTP10D is required for long-term memory in
      Drosophila.
AB  - Tyrosine phosphorylation mediates multiple signal transduction pathways that play
      key roles in developmental processes and behavioral plasticity. The level of
      tyrosine phosphorylation is regulated by protein tyrosine kinases and protein
      tyrosine phosphatases (PTPs). Extensive studies have investigated the roles of
      tyrosine kinases in memory formation. However, there were few studies on PTPs. To
      date, learning has been shown to be defective only for mouse knock-outs of
      PTPalpha, leukocyte common antigen-related, or PTPdelta. A major limitation of
      these studies arises from their inability to distinguish an acute (biochemical)
      impairment of memory formation from a more chronic abnormality in
      neurodevelopment. From a behavioral screen for defective long-term memory, we
      found chi mutants to disrupt expression of the PTP10D protein tyrosine
      phosphatase gene. We show that chi mutants are normal for learning, early memory,
      and anesthesia-resistant memory, whereas long-term memory specifically is
      abolished. Significantly, induction of a heat shock-PTP10D+ transgene before
      training fully rescues the memory defect of chi mutants, thereby demonstrating an
      acute role for PTP10D in behavioral plasticity. We show that PTP10D is widely
      expressed in the embryonic CNS and in the adult brain. Transgenic expression of
      upstream activating sequence-PTP10D+ in mushroom bodies is sufficient to rescue
      the memory defect of chi mutants. Our data clearly demonstrate that signaling
      through PTP10D in mushroom bodies is critical for the formation of long-term
      memory.

PMID- 17442826
TI  - A calcium- and calmodulin-dependent kinase Ialpha/microtubule affinity regulating
      kinase 2 signaling cascade mediates calcium-dependent neurite outgrowth.
AB  - Calcium is a critical regulator of neuronal differentiation and neurite outgrowth
      during development, as well as synaptic plasticity in adulthood. Calcium- and
      calmodulin-dependent kinase I (CaMKI) can regulate neurite outgrowth; however,
      the signal transduction cascades that lead to its physiological effects have not
      yet been elucidated. CaMKIalpha was therefore used as bait in a yeast two-hybrid
      assay and microtubule affinity regulating kinase 2 (MARK2)/Par-1b was identified
      as an interacting partner of CaMKI in three independent screens. The interaction
      between CaMKI and MARK2 was confirmed in vitro and in vivo by
      coimmunoprecipitation. CaMKI binds MARK2 within its kinase domain, but only if it
      is activated by calcium and calmodulin. Expression of CaMKI and MARK2 in Neuro-2A
      (N2a) cells and in primary hippocampal neurons promotes neurite outgrowth, an
      effect dependent on the catalytic activities of these enzymes. In addition,
      decreasing MARK2 activity blocks the ability of the calcium ionophore ionomycin
      to promote neurite outgrowth. Finally, CaMKI phosphorylates MARK2 on novel sites
      within its kinase domain. Mutation of these phosphorylation sites decreases both
      MARK2 kinase activity and its ability to promote neurite outgrowth. Interaction
      of MARK2 with CaMKI results in a novel, calcium-dependent pathway that plays an
      important role in neuronal differentiation.

PMID- 17442827
TI  - Brain-derived neurotrophic factor restores synaptic plasticity in a knock-in
      mouse model of Huntington's disease.
AB  - Asymptomatic Huntington's disease (HD) patients exhibit memory and cognition
      deficits that generally worsen with age. Similarly, long-term potentiation (LTP),
      a form of synaptic plasticity involved in memory encoding, is impaired in HD
      mouse models well before motor disturbances occur. The reasons why LTP
      deteriorates are unknown. Here we show that LTP is impaired in hippocampal slices
      from presymptomatic Hdh(Q92) and Hdh(Q111) knock-in mice, describe two factors
      contributing to this deficit, and establish that potentiation can be rescued with
      brain-derived neurotrophic factor (BDNF). Baseline physiological measures were
      unaffected by the HD mutation, but LTP induction and, to a greater degree,
      consolidation were both defective. The facilitation of burst responses that
      normally occurs during a theta stimulation train was reduced in HD knock-in mice,
      as was theta-induced actin polymerization in dendritic spines. The decrease in
      actin polymerization and deficits in LTP stabilization were reversed by BDNF,
      concentrations of which were substantially reduced in hippocampus of both
      Hdh(Q92) and Hdh(Q111) mice. These results suggest that the HD mutation
      discretely disrupts processes needed to both induce and stabilize LTP, with the
      latter effect likely arising from reduced BDNF expression. That BDNF rescues LTP
      in HD knock-in mice suggests the possibility of treating cognitive deficits in
      asymptomatic HD gene carriers by upregulating production of the neurotrophin.

PMID- 17442828
TI  - Episodic stimulation of alpha1-adrenoreceptors induces protein kinase C-dependent
      persistent changes in motoneuronal excitability.
AB  - In vitro long-term facilitation (ivLTF) is a novel form of activity-independent
      postsynaptic enhancement of AMPA receptor function in hypoglossal (XII)
      motoneurons that can be induced by intermittent activation of 5-HT2 receptors. In
      vivo respiratory long-term facilitation (LTF) is characterized by a persistent 5
      HT2 receptor-dependent increase in respiratory motor output or ventilation after
      episodic exposures to hypoxia in adult rats. Here, we demonstrate that ivLTF can
      also be induced by episodic but not continuous stimulation of alpha1-adrenergic
      receptors that requires protein kinase C (PKC), but not PKA (protein kinase A),
      activation. Additionally, we show that in vivo respiratory LTF is also alpha1
      adrenergic receptor dependent. We suggest that, in vivo, concurrent episodic
      activation of 5-HT2 and alpha1-adrenergic receptors is necessary to produce long
      lasting changes in the excitability of respiratory motoneurons, possibly
      involving PKC activation via the G alpha(q)-PLC (phospholipase C) signaling
      pathway common to both receptor subtypes. Such plasticity of XII motor output may
      increase upper airway muscle (innervated by XII nerve) tone and improve the
      likelihood that airway patency will be maintained. Elucidating the mechanism
      underlying LTF can be of clinical importance to the patients suffering from sleep
      disordered breathing.

PMID- 17442829
TI  - Activation of TRPA1 channel facilitates excitatory synaptic transmission in
      substantia gelatinosa neurons of the adult rat spinal cord.
AB  - TRPA1 is expressed in primary sensory neurons and hair cells, and it is proposed
      to be activated by cold stimuli, mechanical stimuli, or pungent ingredients.
      However, its role in regulating synaptic transmission has never been documented
      yet. In the present study, we examined whether activation of the TRPA1 channels
      affects synaptic transmission in substantia gelatinosa (SG) neurons of adult rat
      spinal cord slices by using the whole-cell patch-clamp technique. A chief
      ingredient of mustard oil, allyl isothiocyanate (AITC), superfused for 2 min
      markedly increased the frequency and amplitude of spontaneous EPSCs (sEPSCs),
      which was accompanied by an inward current. Similar actions were produced by
      cinnamaldehyde and allicin. The AITC-induced increases in sEPSC frequency and
      amplitude were resistant to tetrodotoxin (TTX) and La3+, whereas being
      significantly reduced in extent in a Ca2+-free bath solution. In the presence of
      glutamate receptor antagonists CNQX and AP5, AITC did not generate any synaptic
      activities. The AITC-induced increases in sEPSC frequency and amplitude were
      reduced by ruthenium red, whereas being unaffected by capsazepine. AITC also
      increased the frequency and amplitude of spontaneous inhibitory postsynaptic
      currents; this AITC action was abolished in the presence of TTX or glutamate
      receptor antagonists. These results indicate that TRPA1 appears to be localized
      not only at presynaptic terminals on SG neurons to enhance glutamate release, but
      also in terminals of primary afferents innervating onto spinal inhibitory
      interneurons, which make synapses with SG neurons. This central modulation of
      sensory signals may be associated with physiological and pathological pain
      sensations.

PMID- 17442830
TI  - Suppressed neuronal activity and concurrent arteriolar vasoconstriction may
      explain negative blood oxygenation level-dependent signal.
AB  - Synaptic transmission initiates a cascade of signal transduction events that
      couple neuronal activity to local changes in blood flow and oxygenation. Although
      a number of vasoactive molecules and specific cell types have been implicated,
      the transformation of stimulus-induced activation of neuronal circuits to
      hemodynamic changes is still unclear. We use somatosensory stimulation and a
      suite of in vivo imaging tools to study neurovascular coupling in rat primary
      somatosensory cortex. Our stimulus evoked a central region of net neuronal
      depolarization surrounded by net hyperpolarization. Hemodynamic measurements
      revealed that predominant depolarization corresponded to an increase in
      oxygenation, whereas predominant hyperpolarization corresponded to a decrease in
      oxygenation. On the microscopic level of single surface arterioles, the response
      was composed of a combination of dilatory and constrictive phases. Critically,
      the relative strength of vasoconstriction covaried with the relative strength of
      oxygenation decrease and neuronal hyperpolarization. These results suggest that a
      neuronal inhibition and concurrent arteriolar vasoconstriction correspond to a
      decrease in blood oxygenation, which would be consistent with a negative blood
      oxygenation level-dependent functional magnetic resonance imaging signal.

PMID- 17442831
TI  - Changes in motoneuron properties and synaptic inputs related to step training
      after spinal cord transection in rats.
AB  - Although recovery from spinal cord injury is generally meager, evidence suggests
      that step training can improve stepping performance, particularly after neonatal
      spinal injury. The location and nature of the changes in neural substrates
      underlying the behavioral improvements are not well understood. We examined the
      kinematics of stepping performance and cellular and synaptic electrophysiological
      parameters in ankle extensor motoneurons in nontrained and treadmill-trained
      rats, all receiving a complete spinal transection as neonates. For comparison,
      electrophysiological experiments included animals injured as young adults, which
      are far less responsive to training. Recovery of treadmill stepping was
      associated with significant changes in the cellular properties of motoneurons and
      their synaptic input from spinal white matter [ipsilateral ventrolateral
      funiculus (VLF)] and muscle spindle afferents. A strong correlation was found
      between the effectiveness of step training and the amplitude of both the action
      potential afterhyperpolarization and synaptic inputs to motoneurons (from
      peripheral nerve and VLF). These changes were absent if step training was
      unsuccessful, but other spinal projections, apparently inhibitory to step
      training, became evident. Greater plasticity of axonal projections after neonatal
      than after adult injury was suggested by anatomical demonstration of denser VLF
      projections to hindlimb motoneurons after neonatal injury. This finding confirmed
      electrophysiological measurements and provides a possible mechanism underlying
      the greater training susceptibility of animals injured as neonates. Thus, we have
      demonstrated an "age-at-injury"-related difference that may influence training
      effectiveness, that successful treadmill step training can alter
      electrophysiological parameters in the transected spinal cord, and that
      activation of different pathways may prevent functional improvement.

PMID- 17442832
TI  - AKAP12 regulates human blood-retinal barrier formation by downregulation of
      hypoxia-inducible factor-1alpha.
AB  - Many diseases of the eye such as retinoblastoma, diabetic retinopathy, and
      retinopathy of prematurity are associated with blood-retinal barrier (BRB)
      dysfunction. Identifying the factors that contribute to BRB formation during
      human eye development and maintenance could provide insights into such diseases.
      Here we show that A-kinase anchor protein 12 (AKAP12) induces BRB formation by
      increasing angiopoietin-1 and decreasing vascular endothelial growth factor
      (VEGF) levels in astrocytes. We reveal that AKAP12 downregulates the level of
      hypoxia-inducible factor-1alpha (HIF-1alpha) protein by enhancing the interaction
      of HIF-1alpha with pVHL (von Hippel-Lindau tumor suppressor protein) and PHD2
      (prolyl hydroxylase 2). Conditioned media from AKAP12-overexpressing astrocytes
      induced barriergenesis by upregulating the expression of tight junction proteins
      in human retina microvascular endothelial cells (HRMECs). Compared with the
      retina during BRB maturation, AKAP12 expression in retinoblastoma patient tissue
      was markedly reduced whereas that of VEGF was increased. These findings suggest
      that AKAP12 may induce BRB formation through antiangiogenesis and barriergenesis
      in the developing human eye and that defects in this mechanism can lead to a loss
      of tight junction proteins and contribute to the development of retinal
      pathologies such as retinoblastoma.

PMID- 17442833
TI  - Glucocorticoids enhance the excitability of principal basolateral amygdala
      neurons.
AB  - A large body of pharmaco-behavioral data implicates the basolateral nucleus of
      the amygdala (BLA) in the facilitation of memory consolidation by emotions.
      Overall, this evidence suggests that stress hormones released during emotional
      arousal increase the activity of BLA neurons. In turn, this increased BLA
      activity would facilitate synaptic plasticity elsewhere in the brain, to which
      the BLA projects. However, the direct effects of glucocorticoids on BLA neurons
      are incompletely understood. In the present study, we examined the direct effects
      of corticosterone (CORT) on principal neurons of the rat BLA in vitro using whole
      cell patch-clamp recordings. We found that application of a stress level of CORT
      for 20 min caused significant changes in the passive properties and
      responsiveness of BLA cells measured 1-2 h later. Indeed, CORT application
      produced a depolarization of the resting potential, an increase in input
      resistance, and a dramatic decrease in spike-frequency adaptation. In addition,
      GABA(A) IPSPs evoked by stimulation of the external capsule were significantly
      reduced by CORT application. This effect of CORT was not attributable to a
      reduction in the amount of GABA released because GABA(B) IPSPs were unchanged and
      the resistance drop associated with GABA(A) IPSPs was not altered. Rather, we
      found that this effect of CORT resulted from a positive shift of the GABA(A)
      reversal potential. Overall, these results suggest that, in agreement with
      previous behavioral findings, glucocorticoids enhance the excitability of
      principal BLA cells by increasing their intrinsic excitability and decreasing the
      impact of GABA(A) IPSPs.

PMID- 17442834
TI  - MrgD activation inhibits KCNQ/M-currents and contributes to enhanced neuronal
      excitability.
AB  - The recently identified Mas-related gene (Mrg) family of G-protein-coupled
      receptors is expressed almost exclusively in dorsal root ganglion (DRG) neurons.
      The expression of one family member, MrgD, is even further confined to IB4+,
      nonpeptidergic, small-diameter nociceptors. Although the functional consequences
      of MrgD activation are not known, this expression profile provides intriguing
      potential for a role in pain sensation or modulation. In a recombinant cell line,
      we first assessed the functional significance of MrgD activation by coexpressing
      MrgD with the KCNQ2/3 potassium channel, a channel implicated in pain. Whole-cell
      voltage-clamp recordings revealed that bath application of the ligand for MrgD,
      beta-alanine, resulted in robust inhibition of KCNQ2/3 activity. Pharmacological
      blockade of G(i/o) and phospholipase C signaling revealed a partial and complete
      block of the response, respectively. We extended these observations to
      dissociated DRG neuron cultures by examining MrgD modulation of M-currents
      (carried primarily by KCNQ2/3). Here too, beta-alanine-induced activation of
      endogenous MrgD inhibited M-currents, but primarily via a pertussis toxin
      sensitive pathway. Finally, we assessed the consequence of beta-alanine-induced
      activation of MrgD in phasic neurons. Phasic neurons that fired a single action
      potential (AP) before beta-alanine application fired multiple APs during beta
      alanine exposure. In sum, we provide evidence for a novel interaction between
      MrgD and KCNQ/M-type potassium channels that contributes to an increase in
      excitability of DRG neurons and thus may enhance the signaling of primary
      afferent nociceptive neurons.

PMID- 17442835
TI  - Spanish-language version of the MedRisk Instrument for Measuring Patient
      Satisfaction With Physical Therapy Care (MRPS): preliminary validation.
AB  - BACKGROUND AND PURPOSE: An instrument that provides valid measurements of
      satisfaction with physical therapy care for Spanish-speaking patients will
      enhance communication and ensure their representation in quality assurance
      analyses and research on health care disparities. The purpose of this
      investigation was to provide preliminary information on the factor structure,
      group- and individual-level reliability, and criterion-referenced validity of
      measurements obtained from a Spanish-language version of the MedRisk Instrument
      for Measuring Patient Satisfaction With Physical Therapy Care (MRPS). SUBJECTS: A
      total of 203 Spanish-speaking patients in the New York City area participated in
      this study. METHODS: Consenting subjects completed a 20-item MRPS after discharge
      from outpatient physical therapy care. Several translators performed "forward"
      and "backward" translation of the MRPS, followed by consensus agreement on item
      structure. Factor structure was investigated using item-correlation and
      exploratory factor analysis. Group-level reliability for single test
      administration was assessed using the Cronbach alpha, and individual-level
      reliability was assessed by calculating the standard error of the measure (SEM).
      Concurrent validity was tested by comparing the item scores and mean scores of
      factors to global measures of satisfaction. RESULTS: The means of individual item
      scores (1-5) ranged from 3.22 for "I did not wait too long" to 4.80 for "My
      therapist treated me respectfully." There were no sex-based differences in item
      scores. Exploratory factor analysis suggested a 2-factor solution: a 7-item
      "external" factor and a 3-item "internal" factor. The correlations (r) of the
      mean scores from these factors with the 2 global measures ranged from .59 to .82.
      The SEM was 0.16 for the internal factor and 0.25 for the external factor.
      DISCUSSION AND CONCLUSION: The underlying factor structure of the Spanish
      language version of the MRPS was identical to the English-language version. Our
      findings provide preliminary support for the reliability and validity of
      measurements obtained from the Spanish-language version of the MRPS. Further
      study is needed to assess the stability of these findings in other samples. As
      with English-speaking patients, Spanish-speaking patient's satisfaction with
      physical therapy care is most strongly linked to the professional behavior of the
      clinician.

PMID- 17442836
TI  - Effect of practice on a novel task--walking on a treadmill: preadolescents with
      and without Down syndrome.
AB  - BACKGROUND AND PURPOSE: The authors propose that preadolescents with Down
      syndrome (DS) initially adapt to contexts that challenge their stability by
      increasing stiffness and impulse but, with practice, they will continue to adapt,
      but in the opposite direction, by decreasing stiffness and impulse. The purpose
      of this study was to explore changes in stiffness and impulse values of
      participants with DS after sufficient, task-specific practice distributed over
      time in a motivating environment. SUBJECTS: Eight preadolescents with DS and 8
      preadolescents with typical development (TD) participated. METHODS: At pretest
      and posttest visits, participants walked over ground at their preferred speed and
      on a treadmill at 40%, 75%, and 110% of their over-ground speed. Practice
      included 4 sessions of treadmill walking at 75% of over-ground speed for 12
      minutes, with approximately 800 strides per leg per session. RESULTS: The
      preadolescents with DS had reduced stiffness and impulse values following walking
      practice while still producing kinematic patterns uniquely different from those
      of their peers with TD. DISCUSSION AND CONCLUSION: Preadolescents with DS can
      adjust their dynamic resources, both upward and downward. With practice, they can
      maintain stability while improving efficiency, producing stiffness and impulse
      values more like those of their peers with TD.

PMID- 17442837
TI  - The meaning of rehabilitation in the home environment after acute stroke from the
      perspective of a multiprofessional team.
AB  - BACKGROUND AND PURPOSE: Intervention programs for home-based rehabilitation are
      not fully described in the literature, and rehabilitation team members'
      experiences and tacit understanding of working with patients after stroke in the
      home environment need to be further understood. The aim of this study was to
      identify the meaning of rehabilitation in the home environment after stroke from
      the perspective of members of a multiprofessional team. SUBJECTS: Thirteen
      members of a multiprofessional outreach team (physical therapists, occupational
      therapists, speech and language therapists, and a social worker) working at a
      geriatric hospital in Stockholm, Sweden, participated in the study. METHODS: A
      qualitative method (the Empirical Phenomenological Psychological method) was
      used, with data being obtained from retrospective interviews of the team members
      after completing home-based rehabilitation of patients after acute stroke.
      RESULTS: One main theme ("supporting continuity") and 4 subthemes ("making a
      journey together from hospital to home," "enabling experiences of functioning,"
      "refraining from interventions-encouraging patient problem-solving skills," and
      "looking for a new phase-uncertain endings") were revealed. DISCUSSION AND
      CONCLUSION: The findings suggest that contextual factors, both environmental and
      personal, were considered to be of great importance by the members of the
      multiprofessional team and were accounted for when they were working in the home
      environment in the rehabilitation of patients after stroke. Contextual factors
      detected in the home environment gave valuable information to the team members,
      who used the information in their strategies to assist the patients in finding
      continuity in their daily life and to link the past to the present and the "new
      body" to the "old body."

PMID- 17442838
TI  - Differential diagnosis of endometriosis in a young adult woman with nonspecific
      low back pain.
AB  - BACKGROUND AND PURPOSE: Endometriosis is a common gynecological disorder that can
      cause musculoskeletal symptoms and manifest as nonspecific low back pain. CASE
      DESCRIPTION: The patient was a 25-year-old woman who reported the sudden onset of
      severe left-sided lumbosacral, lower quadrant, buttock, and thigh pain. The
      physical therapist examination revealed findings suggestive of a pelvic visceral
      disorder during the diagnostic process. The physical therapist referred the
      patient for medical consultation, and she was later diagnosed by a gynecologist
      with endometriosis and a left ovarian cyst. OUTCOMES: The patient underwent laser
      laparoscopy and excision of the ovarian cyst followed by a regimen of
      gonadotropin-releasing hormone agonists. The intervention resulted in abolition
      of the lower quadrant pain and a significant reduction of the back and leg pain
      that enabled the patient to return to her normal activities. DISCUSSION: A
      thorough physical therapist examination that considers all of the
      musculoskeletal, visceral, and psychosocial components is essential to identify
      pelvic disorders such as endometriosis and other disease processes during the
      differential diagnosis of nonspecific low back pain. Medical consultation is
      necessary to provide proper diagnosis and intervention of endometriosis, but
      physical therapists also may have an important role in the identification of
      endometriosis and the management of the musculoskeletal aspects of the disorder.

PMID- 17442839
TI  - Sensorimotor impairments and reaching performance in subjects with poststroke
      hemiparesis during the first few months of recovery.
AB  - BACKGROUND AND PURPOSE: Little is known about the relationship between upper
      extremity (UE) sensorimotor impairment and reaching performance during the first
      few months after stroke. The purpose of this study was to examine: (1) how
      measures of UE sensorimotor impairment are related to the speed, accuracy, and
      efficiency of reaching in subjects with hemiparesis during the subacute phase
      after stroke and (2) how impairments measured during the acute phase after stroke
      may predict the variance in reaching performance a few months later. SUBJECTS AND
      METHODS: Upper-extremity sensorimotor impairments and reaching performance were
      evaluated in 39 subjects with hemiparesis at 2 time points: during the acute
      phase (8.7+/-3.6 [X+/-SD] days) and the subacute phase (108.7+/-16.5 days) after
      stroke. Ten subjects who were healthy (control subjects) were evaluated once.
      Regression analyses were used to determine which impairments were the best
      predictors of variance in reaching performance in the subacute phase after
      stroke. RESULTS: Only a small amount of variance (<30%) in reaching performance
      was explained at the subacute time point, using either acute or subacute
      impairments as predictor variables. Of the impairments measured, UE strength
      deficits were the strongest, most consistent predictors of the variance in
      reaching performance during the first 3 months after stroke. DISCUSSION AND
      CONCLUSION: Surprisingly, the detailed clinical assessment of UE sensorimotor
      impairment, measured at the acute or subacute phase after stroke, did not explain
      much of the variance in reaching performance during the subacute phase after
      stroke. The findings that UE strength deficits (ie, decreased active range of
      motion and isometric force production) were the most common predictors of the
      variance in reaching performance during the first 3 months after stroke are
      consistent with the current viewpoint that impaired volitional muscle activation,
      clinically apparent as UE weakness, is a prominent contributing factor to UE
      dysfunction after stroke.

PMID- 17442840
TI  - Neuromuscular training versus strength training during first 6 months after
      anterior cruciate ligament reconstruction: a randomized clinical trial.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine the effect of
      a 6-month neuromuscular training (NT) program versus a traditional strength
      training (ST) program following anterior cruciate ligament (ACL) reconstruction.
      SUBJECTS: Seventy-four subjects with ACL reconstruction participated in the
      study. METHODS: The study was a randomized, single-blinded, controlled trial. The
      NT and ST groups were tested preoperatively and at 3 and 6 months. The main
      outcome measure was the Cincinnati Knee Score. Secondary outcome measures were
      visual analog scales (VASs) for pain and function, the 36-Item Short-Form Health
      Survey (SF-36), hop tests, isokinetic muscle strength, proprioception, and static
      and dynamic balance tests. RESULTS: The NT group demonstrated significantly
      improved Cincinnati Knee Scores and VAS scores for global knee function compared
      with the ST group at the 6-month follow-up. There were no significant differences
      between the groups for the other outcome measures (ie, hop, balance,
      proprioception, and muscle strength tests). DISCUSSION AND CONCLUSION: The
      results of this study suggest that exercises included in the NT program should be
      part of the rehabilitation program following ACL reconstruction.

PMID- 17442841
TI  - Differential intracellular signaling through PAC1 isoforms as a result of
      alternative splicing in the first extracellular domain and the third
      intracellular loop.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP), a pleiotropic
      neuropeptide, performs a variety of physiological functions. The PACAP-specific
      receptor PAC1 has several variants that result mainly from alternative splicing
      in the mRNA regions encoding the first extracellular (EC1) domain and the third
      intracellular cytoplasmic (IC3) loop. The effects on downstream signaling
      produced by combinations of alternative splicing events in the EC1 domain and IC3
      loop have not yet been clarified. In this study, we have used semiquantitative
      reverse transcriptase-polymerase chain reaction (RT-PCR) to examine the tissue
      distributions of four PAC1 isoforms in mice. We then established cell lines
      constitutively expressing each of the PAC1 isoforms and characterized the binding
      properties of each isoform to PACAP-38, vasoactive intestinal polypeptide (VIP),
      and the PAC1-specific agonist maxadilan, as well as the resulting effects on two
      major intracellular signaling pathways: cAMP production and changes in the
      intracellular calcium concentration. The results demonstrate that the variants of
      the IC3 loop affect the binding affinity of the ligands for the receptor, whereas
      the variants of the EC1 domain primarily affect the intracellular signaling
      downstream of PAC1. Accordingly, this study indicates that the combination of
      alternative splicing events in the EC1 domain and the IC3 loop create a variety
      of PAC1 isoforms, which in turn may contribute to the functional pleiotropism of
      PACAP. This study not only contributes to the understanding of the multiple
      functions of PACAP but also helps to elucidate the relationship between the
      structures and functions of G-protein-coupled receptors.

PMID- 17442842
TI  - Rifaximin is a gut-specific human pregnane X receptor activator.
AB  - Rifaximin, a rifamycin analog approved for the treatment of travelers' diarrhea,
      is also beneficial in the treatment of multiple chronic gastrointestinal
      disorders. However, the mechanisms contributing to the effects of rifaximin on
      chronic gastrointestinal disorders are not fully understood. In the current
      study, rifaximin was investigated for its role in activation of the pregnane X
      receptor (PXR), a nuclear receptor that regulates genes involved in xenobiotic
      and limited endobiotic deposition and detoxication. PXR-humanized (hPXR), Pxr
      null, and wild-type mice were treated orally with rifaximin, and rifampicin, a
      well characterized human PXR ligand. Rifaximin was highly concentrated in the
      intestinal tract compared with rifampicin. Rifaximin treatment resulted in
      significant induction of PXR target genes in the intestine of hPXR mice, but not
      in wild-type and Pxr-null mice. However, rifaximin treatment demonstrated no
      significant effect on hepatic PXR target genes in wild-type, Pxr-null, and hPXR
      mice. Consistent with the in vivo data, cell-based reporter gene assay revealed
      rifaximin-mediated activation of human PXR, but not the other xenobiotic nuclear
      receptors constitutive androstane receptor, peroxisome proliferator-activated
      receptor (PPAR)alpha, PPARgamma, and farnesoid X receptor. Pretreatment with
      rifaximin did not affect the pharmacokinetics of the CYP3A substrate midazolam,
      but it increased the C(max) and decreased T(max) of 1'-hydroxymidazolam.
      Collectively, the current study identified rifaximin as a gut-specific human PXR
      ligand, and it provided further evidence for the utility of hPXR mice as a
      critical tool for the study of human PXR activators. Further human studies are
      suggested to assess the potential role of rifaximin-mediated gut PXR activation
      in therapeutics of chronic gastrointestinal disorders.

PMID- 17442843
TI  - Proteomic analysis of alternative protein tyrosine phosphorylation in 1,2
      dichlorovinyl-cysteine-induced cytotoxicity in primary cultured rat renal
      proximal tubular cells.
AB  - Toxicant exposure affects the activity of various protein tyrosine kinases. Using
      phosphotyrosine proteomics, we identified proteins that were differentially
      phosphorylated before renal cell detachment and apoptosis. Treatment of primary
      cultured rat proximal tubular epithelial cells with the model nephrotoxicant S
      (1,2-dichlorovinyl)-L-cysteine (DCVC) resulted in early reorganization of F-actin
      stress fibers and formation of lamellipodia, which was followed by cell
      detachment from the matrix and apoptosis. This was prevented by genistein
      mediated inhibition of protein tyrosine kinases and enhanced by inhibition of
      protein tyrosine phosphatases using vanadate. Phosphotyrosine proteomics revealed
      that DCVC-induced renal cell apoptosis was preceded by changes in the tyrosine
      phosphorylation status of a subset of proteins, as identified by matrix-assisted
      laser desorption ionization/time of flight-mass spectrometry (MS)/MS including
      actin-related protein 2 (Arp2), cytokeratin 8, t-complex protein 1 (TCP-1),
      chaperone containing TCP-1, and gelsolin precursor. The major differentially
      tyrosine-phosphorylated protein was Arp2, whereas phosphorylation of Arp3 was not
      affected. Arp2 was located in the lamellipodia that were formed before the onset
      of apoptosis. Because DCVC-induced cell detachment and apoptosis is regulated by
      tyrosine kinases, we propose that alterations in tyrosine phosphorylation of a
      subset of proteins, including Arp2, play a role in the regulation of the F-actin
      reorganization and lamellipodia formation that precede renal cell apoptosis
      caused by nephrotoxicants.

PMID- 17442844
TI  - Comparison of an ESAT-6/CFP-10 peptide-based enzyme-linked immunospot assay to a
      tuberculin skin test for screening of a population at moderate risk of
      contracting tuberculosis.
AB  - Screening for latent tuberculosis infection (LTBI) with the Mantoux tuberculin
      skin test (TST) has many limitations including false-positive results due to
      Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccination. Three hundred
      ninety adult inmates with normal screening chest radiographs in a county jail
      were evaluated for LTBI using TST and an ESAT-6/CFP-10 peptide-based enzyme
      linked immunospot assay (T-SPOT.TB). LTBI prevalence rates were 19.0% and 8.5% by
      T-SPOT.TB and TST, respectively. Overall agreement between test results was 82.8%
      (kappa = 0.29). Positive T-SPOT.TB results were significantly associated with
      increased age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.06)
      and intravenous drug use history (OR, 2.92; 95% CI, 1.36 to 6.27). Positive TST
      results were significantly associated with increased age (OR, 1.06; 95% CI, 1.02
      to 1.09) and foreign birth (OR, 6.61; 95% CI, 1.98 to 22.01). Discordant
      covariates between the assay results included increased age (OR, 0.96; 95% CI,
      0.94 to 0.99) and intravenous drug use history (OR, 0.41; 95% CI, 0.19 to 0.88).
      T-SPOT.TB reactivity is unaffected by prior BCG vaccination. T-SPOT.TB may be
      more sensitive than TST in diagnosing LTBI among a moderate risk population of
      inmates, particularly those with intravenous drug use history. Longitudinal
      studies are needed to assess the positive predictive value of T-SPOT.TB in
      identifying those most likely to convert to active disease in general populations
      as well as in high-risk subpopulations.

PMID- 17442845
TI  - Cellular and humoral immune responses to alphavirus replicon vaccines expressing
      cytomegalovirus pp65, IE1, and gB proteins.
AB  - Development of vaccines against cytomegalovirus (CMV) is an important public
      health priority. We used a propagation-defective, single-cycle RNA replicon
      vector system derived from an attenuated strain of an alphavirus, Venezuelan
      equine encephalitis virus, to produce virus-like replicon particles (VRP)
      expressing various combinations of pp65, IE1, or gB proteins of human CMV.
      Protein expression in VRP-infected cells was highest with single-promoter
      replicons expressing pp65, IE1, a pp65/IE1 fusion protein, or the extracellular
      domain of gB and with double-promoter replicons expressing pp65 and IE1. Protein
      expression was lower with double- and triple-promoter replicons expressing gB,
      especially the full-length form of gB. BALB/c mice immunized with VRP expressing
      gB developed high titers of neutralizing antibody to CMV, and mice immunized with
      VRP expressing pp65, IE1, or a pp65/IE1 fusion protein developed robust antigen
      specific T-cell responses as measured by gamma interferon enzyme-linked
      immunospot assay. Three overlapping immunodominant pp65 peptides contained a nine
      amino-acid sequence (LGPISGHVL) that matches the consensus binding motif for a
      major histocompatibility complex H2-D(d) T-cell epitope. These data provide the
      basis for further development and clinical evaluation of an alphavirus replicon
      vaccine for CMV expressing the pp65, IE1, and gB proteins.

PMID- 17442846
TI  - Immunohematological reference values for healthy adults in Burkina Faso.
AB  - Reference ranges for peripheral blood lymphocyte subsets were generated for 186
      healthy adults in Burkina Faso using single-platform flow cytometry. CD4(+) T
      cell counts ranged from 631 to 1,696 cells microl(-1); they were lower in males
      (n = 97) than in females (n = 89), whereas natural killer cell counts were
      higher.

PMID- 17442847
TI  - Evaluation of a simplified dual-platform flow cytometric method for measurement
      of lymphocyte subsets and T-cell maturation phenotypes in the population of
      Nouna, Burkina Faso.
AB  - In the context of a larger clinical study in Nouna, Burkina Faso, we evaluated a
      simplified dual-platform (DP) flow cytometric (FCM) method that allows the
      determination of major lymphocyte subsets in a single test tube. We compared the
      phenotyping of lymphocytes with DP FCM and simultaneous measurements with
      standard single-platform (SP) FCM for samples from 177 individuals. Analysis of
      the comparative measurements revealed that DP FCM systematically underestimates
      the proportion of NK cells, overestimates the percentage of CD3(+) CD8(+)
      lymphocytes, and yields proportions of B cells and CD4(+) T cells comparable with
      the results from SP FCM. Bland-Altman analysis showed a low bias between both
      methods and an acceptable precision for percent values of CD4(+) T cells (bias +/
      precision, -1% +/- 6%) and CD8(+) T cells (-3% +/- 6%). The absolute cell
      numbers of all lymphocyte subpopulations, however, were systematically biased
      towards lower values being obtained by DP FCM. Reference values for the
      distribution of T-cell maturation phenotypes in 177 healthy adults were
      calculated using DP FCM. The mean +/- standard deviation (SD) CD4(+)-to-CD8(+) T
      cell ratio was 1.61 +/- 0.61, the mean percentage +/- SD of CD4(+) T cells was
      42% +/- 7%, and that of CD8(+) T cells 29% +/- 7%. Among CD4(+) lymphocytes, 28%
      +/- 7% were classified as central memory (CD45RA(low) CCR7(+)), 22% +/- 10% as
      naive (CD45RA(high) CCR7(+)), 45% +/- 12% as effector memory (CD45RA(low) CCR7(
      )); and 5% +/- 3% as terminally differentiated effector memory expressing CD45RA
      (CD45RA(high) CCR7(-)). Among CD8(bright) lymphocytes, 3% +/- 2% had a central
      memory phenotype, 27% +/- 13% were naive, 37% +/- 13% had an effector memory
      phenotype, and 34% +/- 12% were terminally differentiated effector memory cells
      expressing CD45RA.

PMID- 17442848
TI  - Rapid detection of hepatitis B virus surface antigen by an agglutination assay
      mediated by a bispecific diabody against both human erythrocytes and hepatitis B
      virus surface antigen.
AB  - Bispecific antibodies have immense potential for use in clinical applications. In
      the present study, a bispecific diabody against human red blood cells (RBCs) and
      hepatitis B virus surface antigen (HBsAg) was used to detect HBsAg in blood
      specimens. The bispecific diabody was constructed by crossing over the variable
      region of the heavy chains and the light chains of anti-RBC and anti-HBsAg
      antibodies with a short linker, SRGGGS. In enzyme-linked immunosorbent assays,
      this bispecific diabody showed specific binding to both RBCs and HBsAg. When this
      bispecific diabody was mixed with human blood specimens in the presence of HBsAg,
      the dual binding sites of the diabody caused agglutination of human RBCs. This
      diabody-mediated agglutination assay was then used to test 712 clinical blood
      specimens and showed 97.7% sensitivity and 100% specificity when the results were
      compared with those of the conventional immunoassay, which was used as a
      reference. This autologous RBC agglutination assay provides a simple approach for
      rapid screening for HBsAg in blood specimens.

PMID- 17442850
TI  - A novel method to isolate primordial germ cells and its use for the generation of
      germline chimeras in chicken.
AB  - A novel method was developed to isolate chick primordial germ cells (PGCs) from
      circulating embryonic blood. This is a very simple and rapid method for the
      isolation of circulating PGCs (cPGCs) using an ammonium chloride-potassium (ACK)
      buffer for lysis of the red blood cells. The PGCs were purified as in vitro
      culture proceeded. Most of the initial red blood cells were removed in the first
      step using the ACK lysis buffer. The purity of the cPGCs after ACK treatment was
      57.1%, and the recovery rate of cPGCs from whole blood was 90.3%. The ACK process
      removed only red blood cells and it did not affect cPGC morphology. In the second
      step, the red blood cells disappeared as the culture progressed. At 7 days of in
      vitro culture, the purity of the PGCs was 92.9%. Most of these cells expressed
      germline-specific antibodies, such as those against chicken vasa homolog (CVH).
      The cultured PGCs expressed the Cvh and Dazl genes. Chimeric chickens were
      produced from these cultured PGCs, and the donor cells were detected in the
      gonads, suggesting that the PGCs had biological function. In conclusion, this
      novel isolation system for PGCs should be easier to use than previous methods.
      The results of the present study suggest that this novel method will become a
      powerful tool for germline manipulation in the chicken.

PMID- 17442849
TI  - Antimetabolite therapy for lesser-risk B-lineage acute lymphoblastic leukemia of
      childhood: a report from Children's Oncology Group Study P9201.
AB  - Pediatric Oncology Group (POG) protocol 9201 enrolled children with lesser-risk B
      lineage acute lymphoblastic leukemia (ALL) defined by age (1-9), white blood cell
      count (WBC) less than 50 x 10(9)/L (50,000/microL), DNA findings of trisomies 4
      and 10 (or DNA index > 1.16), and lack of overt central nervous system (CNS)
      leukemia. After vincristine, prednisone, and asparaginase induction, 650 of 653
      eligible patients attained remission (3 induction deaths) and received 6 courses
      of intravenous methotrexate (1 g/m(2)) with daily mercaptopurine. Weekly
      intramuscular methotrexate was added during maintenance; pulses of vincristine
      and prednisone were administered with periodic intrathecal chemotherapy.
      Treatment duration was 2.5 years. No alkylators, epipodophylotoxins,
      anthracyclines, or radiation were given. The 6-year event-free survival (EFS) was
      86.6% with overall survival (OS) of 97.2%. Patients with less than 5% marrow
      blasts on induction day 15 had superior EFS. A difference not reaching
      conventional statistical significance (P = .068) was noted for superior outcomes
      in patients with trisomies of chromosomes 4 and 10 versus those lacking double
      trisomies. Sex, ethnicity, CNS status, and WBC were not predictive. This
      indicates the great majority of children with lesser-risk B-lineage ALL are
      curable without agents with substantial late effects.

PMID- 17442851
TI  - Polyunsaturated fatty acids in male and female reproduction.
AB  - In Westernized societies, average consumption of n-6 polyunsaturated fatty acids
      (PUFAs) far exceeds nutritional requirements. The ratio of n-6 to n-3 PUFAs is
      generally >10:1 whereas on a primitive human diet it was closer to 1:1. Diets fed
      to intensively farmed livestock have followed a similar trend. Both n-6 and n-3
      PUFAs can influence reproductive processes through a variety of mechanisms. They
      provide the precursors for prostaglandin synthesis and can modulate the
      expression patterns of many key enzymes involved in both prostaglandin and
      steroid metabolism. They are essential components of all cell membranes. The
      proportions of different PUFAs in tissues of the reproductive tract reflect
      dietary consumption. PUFA supplements (particularly n-3 PUFAs in fish oil) are
      promoted for general health reasons. Fish oils may also benefit fertility in
      cattle and reduce the risk of preterm labor in women, but in both cases current
      evidence to support this is inconclusive. Gamma-linolenic acid containing oils
      can alter the types of prostaglandins produced by cells in vitro, but published
      data to support claims relating to effects on reproductive health are lacking.
      Spermatozoa require a high PUFA content to provide the plasma membrane with the
      fluidity essential at fertilization. However, this makes spermatozoa particularly
      vulnerable to attack by reactive oxygen species, and lifestyle factors promoting
      oxidative stress have clear associations with reduced fertility. Adequately
      powered trials that control for the ratios of different PUFAs consumed are
      required to determine the extent to which this aspect of our diets does influence
      our fertility.

PMID- 17442852
TI  - Sperm motility defects and infertility in male mice with a mutation in Nsun7, a
      member of the Sun domain-containing family of putative RNA methyltransferases.
AB  - Poor sperm quality is the major cause of infertility in humans. Other than sex
      linked factors, the genetic basis for male infertility is poorly defined, largely
      due to practical difficulties in studying the inheritance of this trait in
      humans. As an alternative, we have conducted forward genetic screens in mice to
      generate relevant models. We report on the identification and characterization of
      a chemically-induced mutation, Ste5Jcs1, which causes affected male mice to be
      sterile or subfertile. Mutant sperm exhibited depressed progressive motility
      associated with a rigid flagellar midpiece (but not principal piece) segment,
      which could not be rescued by treatment with agents that stimulate cAMP or
      calcium signaling pathways. Overall mutant sperm ultrastructure appeared normal,
      including the axoneme, although the midpiece mitochondrial sheath showed abnormal
      electron density patterns. Positional cloning of Ste5Jcs1 led to the
      identification of a mutation in a novel gene called Nsun7, which encodes a
      protein with a Sun domain that is homologous to tRNA and rRNA cytosine
      methyltransferases. Therefore, Ste5Jcs1 mutation uncovers a previously
      unrecognized biological process in sperm that underscores the functional
      compartmentalization of the midpiece and principal piece of the flagellum.

PMID- 17442853
TI  - An impaired breeding phenotype in mice with a genetic deletion of beta-2
      microglobulin and diminished MHC class I expression: role in reproductive
      fitness.
AB  - Beta-2 microglobulin (B2M) plays a pivotal role in the biology of mammals,
      including its association with major histocompatibility complex (MHC) Class I
      gene products. The latter molecules have been shown to affect reproduction in
      both mice and humans, although the exact mechanism is still unknown. Here we
      report the results of a longitudinal study of the reproductive performance of a
      genetically modified B2m deficient mouse strain with low MHC Class I expression.
      Our data show that this mouse strain has an impaired reproductive performance.
      However, the mice superovulate well and show a normal estrous cycle. Breeding
      studies from crosses between the transgenic mice and the wild-type parental
      strain show that B2m deficient mice have a significantly lower frequency of
      mating than the control B2m+/+ mice. In addition, the litter size and weaning
      success of B2m deficient mice were lower than the control. Perinatal lethality of
      the B2m deficient offspring was also inflicted by cannibalism of the young pups
      by the B2m deficient female. The impaired breeding phenotype (IBP) can be
      reversed by reintroducing the B2m gene in F1 heterozygous B2m+/- animals; thus
      the presence of B2M confers a normal breeding pattern. The acquisition of an
      impaired breeding phenotype (IBP) as a result of the knockout of B2m directly
      implicates B2M in the reproductive cycle of mice and raises the possibility of an
      effect of B2M on the reproduction of other mammals.

PMID- 17442854
TI  - Oxytocin and vasopressin stimulate anion secretion by human and porcine vas
      deferens epithelia.
AB  - Experiments were conducted to characterize the effects of oxytocin (OT) and
      vasopressin (VP) on epithelial cells isolated from human (1 degree HVD) and
      porcine (1 degree PVD) vas deferens and an immortalized epithelial cell line
      derived from porcine vas deferens (PVD9902 cells). Cultured monolayers were
      assessed in modified Ussing flux chambers and the OT- or VP-induced change in
      short circuit current (I(SC)) was recorded. All cell types responded to
      basolateral OT or VP with a transient increase in I(SC) that reached a peak of 3
      5 microA cm(-2). Concentration-response curves constructed with 1 degree PVD and
      PVD9902 cells revealed that the apparent K(D) (k(app)) for OT was approximately
      100-fold less than the k(app) for VP. Amplicons for the OT receptor (OXTR) and
      vasopressin type 2 and type 1a receptors (AVPR2 and AVPR1A) were generated with
      RT-PCR and the identification of each amplicon confirmed by sequence analysis. A
      selective antagonist for OXTR and AVPR1A fully blocked the effects of OT and
      partially blocked the effects of VP when assessed in both 1 degree PVD and
      PVD9902 monolayers. APVR2 antagonists blocked the effects of low (< or =30 nM)
      but not high concentrations of VP, indicating that VP was affecting both AVPR2
      and a second receptor subtype, likely OXTR or AVPR1A. Experiments employing
      chelerythrine demonstrated that OT stimulation of vas deferens monolayers
      requires PKC activity. Alternatively, VP (but not OT) increased the accumulation
      of cytosolic cAMP in vas deferens epithelial cells. Results from this study
      demonstrate that OT and VP can modulate ion transport across vas deferens
      epithelia by independent mechanisms. OT and VP have the potential to acutely
      change the environment to which sperm are exposed and thus, have the potential to
      affect male fertility.

PMID- 17442855
TI  - Caspase-1 inflammasomes in infection and inflammation.
AB  - Nucleotide-binding and oligomerization domain-like receptors (NLRs) constitute a
      family of germline-encoded pattern-recognition receptors, which allow the host to
      respond rapidly to a wide variety of pathogenic microorganisms. Here, we discuss
      recent advances in the study of a subset of NLRs, which control the activation of
      caspase-1 through the assembly of large protein complexes, inflammasomes. The
      NALP1b inflammasome recognizes anthrax lethal toxin, and flagellin from
      Salmonella and Legionella induces assembly of the Ipaf inflammasome.
      Cryopyrin/NALP3 mediates caspase-1 activation in response to a wide variety of
      bacterial ligands, imidazoquinolines, dsRNA, and the endogenous danger signal
      uric acid. The importance of these cytosolic receptors in immune regulation is
      underscored by the identification of mutations in cryopyrin/NALP3, which are
      genetically linked to human autoinflammatory disorders.

PMID- 17442857
TI  - Anti-CD44-mediated blockade of leukocyte migration in skin-associated immune
      diseases.
AB  - CD44 plays an important role in leukocyte extravasation, which is fortified in
      autoimmune diseases and delayed-type hypersensitivity (DTH) reactions. There is
      additional evidence that distinct CD44 isoforms interfere with the extravasation
      of selective leukocyte subsets. We wanted to explore this question in alopecia
      areata (AA), a hair-follicle centric autoimmune disease, and in a chronic eczema.
      The question became of interest because AA is treated efficiently by topical
      application of a contact sensitizer, such that a mild DTH reaction is maintained
      persistently. Aiming to support the therapeutic efficacy of a chronic eczema in
      AA by anti-CD44 treatment, it became essential to control whether a blockade of
      migration, preferentially of AA effector cells, could be achieved by CD44 isoform
      specific antibodies. Anti-panCD44 and anti-CD44 variant 10 isoform (CD44v10)
      inhibited in vitro migration of leukocytes from untreated and allergen-treated,
      control and AA mice. In vivo, both antibodies interfered with T cell and monocyte
      extravasation into the skin; only anti-panCD44 prevented T cell homing into lymph
      nodes. Contributing factors are disease-dependent alterations in
      chemokine/chemokine receptor expression and a blockade of CD44 on endothelial
      cells and leukocytes. It is important that CD44 can associate with several
      integrins and ICAM-1. Associations depend on CD44 activation and vary with CD44
      isoforms and leukocyte subpopulations. CD44 standard isoform preferentially
      associates with CD49d in T cells and CD44v10 with CD11b in monocytes.
      Accordingly, anti-panCD44 and anti-CD49d inhibit T cell, anti-CD11b, and anti
      CD44v10 macrophage migration most efficiently. Thus, allergen treatment of AA
      likely can be supported by targeting AA T cells selectively via a panCD44-CD49d
      bispecific antibody.

PMID- 17442856
TI  - Modulation of dendritic cell maturation and function by the Tax protein of human
      T cell leukemia virus type 1.
AB  - Human T cell leukemia virus type 1-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) is characterized by the generation of an intense CTL cell
      response directed against the viral transactivator protein Tax. In addition,
      patients diagnosed with HAM/TSP exhibit rapid activation and maturation of
      dendritic cells (DC), likely contributing to the robust, Tax-specific CTL
      response. In this study, extracellular Tax has been shown to induce maturation
      and functional alterations in human monocyte-derived DC, critical observations
      being confirmed in freshly isolated myeloid DC. Tax was shown to promote the
      production of proinflammatory cytokines and chemokines involved in the DC
      activation process in a dose- and time-dependent manner. Furthermore, Tax induced
      the expression of DC activation (CD40, CD80, and CD86) and maturation (CD83)
      markers and enhanced the T cell proliferation capability of DC. Heat inactivation
      of Tax resulted in abrogation of these effects, indicating a requirement for the
      native structure of Tax, which was found to bind efficiently to the DC membrane
      and was internalized within a few hours, suggesting that extracellular Tax may
      possess an intracellular mechanism of action subsequent to entry. Finally,
      inhibitors of cellular signaling pathways, NF-kappaB, protein kinase, tyrosine
      kinase, and phospholipase C, were shown to inhibit Tax-mediated DC activation.
      This is the first study reporting the immunomodulatory effects of extracellular
      Tax in the DC compartment. These results suggest that DC, once exposed to Tax by
      uptake from the extracellular environment, can undergo activation, providing
      constant antigen presentation and costimulation to T cells, leading to the
      intense T cell proliferation and inflammatory responses underlying HAM/TSP.

PMID- 17442859
TI  - Reformulation of a methodological concept in grounded theory.
AB  - Although the grounded theory method was not designed with nursing science in
      mind, it is one of the most prevalent and theory-producing qualitative methods in
      nursing. Changes in the grounded theory methodology have been debated in numerous
      articles. What has not received much attention, however, is a central idea of the
      grounded theory method - the basic social process. The goal here is to raise for
      consideration the idea that change is needed in nurse researchers' understanding
      of the basic social process; there is a need to reformulate this substantive
      concept of the grounded theory method so as to render it more congruent with
      nursing ontology and productive of nursing knowledge.

PMID- 17442861
TI  - Living attentive presence and changing perspectives with a web-based nursing
      theory course.
AB  - Online education can be a wonderful teaching-learning experience for professors
      and students alike. This column shares excerpts from postings that students and a
      professor wrote during an online nursing theories course with the intention to
      illuminate selected essences, paradoxes, and processes of Parse's teaching
      learning model and to portray living attentive presence and changing perspectives
      with online teaching-learning strategies. This reflection was initiated in
      Pittsburgh, Pennsylvania at the Institute of Human Becoming when two of the
      authors (Aquino-Russell and Maillard Struby) were introduced to the human
      becoming teaching-learning model by nurse theorist Rosemarie Rizzo Parse.

PMID- 17442860
TI  - Evidence-based practice: ethical questions for nursing.
AB  - Evidence-based nursing practice is a global phenomenon, the purpose of which is
      to standardize and guide nursing practice based on exclusionary quantitative
      scientific inquiry. What are the origins of this standard terminology found in
      medicine, nursing, and other healthcare professions? What are the educational and
      ethical implications for evidence-based nursing practice from a nursing
      theoretical perspective? The author will begin a discussion of ethical questions
      for the discipline to consider as the evidence-based practice movement gains
      momentum in healthcare arenas worldwide.

PMID- 17442863
TI  - Nursing, healthcare, and culture: a view for the year 2050 from Colombia.
AB  - This column presents a dialogue with Colombian nurse scholar Maria Elisa Moreno,
      who shares her vision and understanding of her country's vision of nursing,
      healthcare, and quality of life in the year 2050.

PMID- 17442864
TI  - Hope in "Rita Hayworth and Shawshank Redemption": a human becoming hermeneutic
      study.
AB  - This article is the report of the human becoming hermeneutic method study on
      "Rita Hayworth and Shawshank Redemption" (the short story, the screenplay, and
      the film). The study unfolded during the Parse-King dialogue that answered the
      research question what is hope as humanly lived? Emergent meanings were
      discovered that enhanced knowledge and understanding of hope in general and
      expanded the human becoming school of thought.

PMID- 17442865
TI  - The art of nursing: communication and self-expression.
AB  - Nursing is considered both an art and a science, yet the nature of art and
      science has been historically depicted as two distinct fields of inquiry in the
      health professions. To meet the health challenges of the future, blending science
      and art through nursing theory, research, and practice is critical. This article
      describes how nurses in a master's of nursing program at Dalhousie University
      broke with tradition for the practicum course to articulate and apply the
      theoretical elements of knowing using aesthetic inquiry. The challenge was in
      articulating and guiding students through the theory of aesthetic knowing, the
      linkages with the fine arts, and the conceptualization of nursing art.

PMID- 17442866
TI  - Improving external and internal validity of a model of midlife women's maternal
      student role stress.
AB  - This study's purpose was to improve both the external and internal validity of
      Gigliotti's model of maternal-student role stress in midlife women. It was found
      that the model is generalizeable to midlife women who are non-degreed
      undergraduate students of varied marital and immigration status and varied
      college major, thus improving external validity. It was also found that
      investigating particular types of children's situation-specific social support
      improved internal validity. These results support the propositions of the Neuman
      systems model as well as Meleis and others' transition framework. An
      interventional study is proposed as the next step in this program of research.

PMID- 17442867
TI  - A research synthesis overview.
AB  - The volume of research literature is enormous, so keeping up with the latest
      studies is difficult. Systematic reviews are a form of research that pools the
      results of multiple studies. Quantitative reviews statistically pool results, and
      qualitative reviews narratively pool results. Reviews are becoming common, but
      some nurses may be unaware of what a systematic review is and how to conduct one.
      The aim of this overview is to acquaint nurses with qualitative systematic
      reviews (research syntheses) by providing information about where to begin a
      synthesis, the stages of the synthesis process, and how to write a manuscript to
      report synthesis results.

PMID- 17442868
TI  - Nursing in Korea.
AB  - Nursing in Korea with support from the federal government is shifting focus to
      better address the needs of an aging population, in particular the increasing
      number of persons with dementia. The family in Korea is struggling to balance
      family caregiving obligations with the demands of employment in a competitive
      world economy. Nurses are in an ideal position to not only teach families how
      best to assist family members with dementia but also how to find meaning in
      caregiving.

PMID- 17442869
TI  - Reducing the burden of dementia in Korea.
AB  - There has been a dramatic increase in the number of persons with dementia in
      Korea, and the number is expected to continue to increase. Dementia is
      increasingly a condition for which there are effective treatments and services.
      Because most adults work full-time in addition to having other family
      responsibilities, the government of Korea and the community are more involved in
      helping persons with dementia, than in the past. Nurses are needed to help with
      dementia research, public policy, education, and healthcare in Korea and
      elsewhere.

PMID- 17442872
TI  - A tale of two telescopes: far in and far out.

PMID- 17442873
TI  - A novel stentless mitral valve.
AB  - Stentless mitral valves have found little clinical utility to date due to
      difficulty in insertion. A new design for a stentless mitral valve, a
      modification of an existing aortic stentless prosthesis, is described. The new
      design mimics the native mitral physiology, and its insertion is easier than with
      existing stentless mitral valves. Commercially available stentless aortic valves
      were inserted into 2 pigs. The valves were modified so that the commissural posts
      were restrained. The valves were partially recessed into the left ventricular
      cavity, secured to the annulus, and anchored to the native papillary muscles.
      Both pigs were weaned from bypass successfully, and both valves functioned
      normally with trace regurgitation noted on echocardiography. This design affords
      the benefit of the reapproximation of native physiology. Preservation of
      papillary-annular continuity should allow maximal left ventricular function. Lack
      of a stent should allow avoidance of long-term anticoagulation.

PMID- 17442874
TI  - Advanced laparoscopic surgery in a free-standing ambulatory setting: lessons from
      the first 50 cases.
AB  - To decrease the impact and cost of surgery, there is a trend toward developing
      treatment models for complex conditions on a fully outpatient basis. This is a
      retrospective study of the initial experience of advanced laparoscopic procedures
      performed on a same-day outpatient basis in the ambulatory campus of a university
      hospital. Over 3 years, 55 patients underwent 50 Nissen fundoplications and 5
      adrenalectomies. There were 2 intraoperative complications, with no mortality and
      no conversion. The median postoperative stay was 4.5 hours. Readmission at 1
      month was 11%. Data on the nursing postoperative telephone follow-up were
      available for 50 patients; 34 (62%) were successfully contacted. Twenty four
      (70%) had no complaint. Preliminary high-level cost data indicate a cost
      advantage. Advanced laparoscopic procedures can be done safely in a pure
      ambulatory setting; the current readmission rate can be reduced with improved
      pain management and better telephone follow-up strategies. Cost savings are
      likely.

PMID- 17442875
TI  - Laparoscopic transgastric repair of a gastrogastric fistula after gastric bypass:
      a novel technique.
AB  - Gastrogastric fistulas are an uncommon complication following laparoscopic Roux-Y
      gastric bypass surgery (LRYGB) and may be caused by staple-line dehiscence or
      leak. Described here is a novel technique to treat these fistulae via a
      laparoscopic transgastric approach and closure of the fistulous tract with an
      Endo Stitch device. The 33-year-old patient, post LRYGB in 2002, with documented
      gastrogastric fistula, had failed non-operative management. A transoral endoscope
      was passed into the cephalad portion of the gastrogastric fistula; a glidewire
      was passed from the gastric pouch into the gastric remnant. Laparoscopically, 2
      gastrotomies were made and a "pneumogastrium" created with carbon dioxide. Under
      direct, transgastric visualization, the distal portion of the gastrogastric
      fistula was closed using an Endo Stitch device. This technique is safe and
      reproducible when performed by an experienced laparoscopic surgeon and could be
      modified for other scenarios requiring alternate access to the stomach.

PMID- 17442876
TI  - The role of laparoscopic surgery in the management of tubal prolapse: a 7 case
      series and literature review.
AB  - Fallopian tube prolapse is an unusual complication after hysterectomy. Different
      surgical options have been proposed, including abdominal, vaginal, and combined
      laparoscopic approaches, with partial or complete salpingectomy. This article
      presents experience in the management of 7 cases of fallopian tube prolapse with
      different surgical approaches according to the characteristics of the case.
      Additionally, 6 cases were reported in the English literature between 1960 and
      2006 that required a second procedure after vaginal partial salpingectomy, and
      the causes of failure were reviewed. It is suggested that the choice between
      abdominal, vaginal, and combined laparoscopic approach with partial or complete
      salpingectomy in the management of prolapsed tubes must be decided individually,
      according to the patient's characteristics and the presenting symptoms.
      Laparoscopic surgery has a role in cases with dense intraperitoneal adhesions. It
      safely enables the mobilization of the prolapsed tube, allowing complete removal
      of the structure and resolution of symptoms.

PMID- 17442877
TI  - Virtual colonoscopy in colorectal cancer screening.
AB  - Colorectal cancer is the third most commonly diagnosed tumor in both males and
      females in the United States. Current modalities for colorectal cancer screening
      include fecal occult blood testing, flexible sigmoidoscopy, double-contrast
      barium enema, and colonoscopy. Virtual colonoscopy is a promising new method for
      assessing the entire colon. Vining and Gelfand first described this technique in
      1994. Since then, virtual colonoscopy has been shown to be extremely safe and
      well tolerated by patients. Indications for virtual colonoscopy include screening
      for polyps, incomplete or failed colonoscopy, and preoperative assessment of the
      colon proximal to an occlusive cancer or even redundant fixed or stenotic colon
      that cannot be endoscopically traversed. Virtual colonoscopy may dramatically
      increase patient participation in screening programs, leading to early diagnosis
      of colorectal cancer. Although virtual colonoscopy seems a potentially attractive
      screening method for colorectal cancer, the cost-effectiveness of this method is
      yet to be determined.

PMID- 17442878
TI  - Regional variation in surgery for gastroesophageal reflux disease in Ontario.
AB  - The optimal treatment for gastroesophageal reflux disease (GERD) is unclear, and
      the degree of variation in the rate of antireflux surgery in different regions is
      unknown. Large variation has significant implications for health care spending
      and may represent uncertainty among health care providers. The objective of this
      study was to identify population-based utilization and measure area rate
      variations in the use of GERD surgery; 11,685 primary antireflux procedures in
      the provincial administrative health databases were studied. Small-area variation
      was quantified using 4 measures. The crude rate of antireflux procedures was
      11.6/100 000 adults. Patients between the ages of 45 and 64 had the highest rates
      of surgery. More women than men underwent antireflux surgery (13.6 vs. 9.4 per
      100,000). Between counties, adjusted surgical rates ranged from 5.0 to 28.7 per
      100,000 persons. Significant regional variation exists for antireflux surgery
      across Ontario, suggesting that its appropriate role in the management of GERD
      remains ill-defined.

PMID- 17442879
TI  - Auto identification technology and its impact on patient safety in the Operating
      Room of the Future.
AB  - Automatic identification technologies, such as bar coding and radio frequency
      identification, are ubiquitous in everyday life but virtually nonexistent in the
      operating room. User expectations, based on everyday experience with automatic
      identification technologies, have generated much anticipation that these systems
      will improve readiness, workflow, and safety in the operating room, with minimal
      training requirements. We report, in narrative form, a multi-year experience with
      various automatic identification technologies in the Operating Room of the Future
      Project at Massachusetts General Hospital. In each case, the additional human
      labor required to make these ;labor-saving' technologies function in the medical
      environment has proved to be their undoing. We conclude that while automatic
      identification technologies show promise, significant barriers to realizing their
      potential still exist. Nevertheless, overcoming these obstacles is necessary if
      the vision of an operating room of the future in which all processes are
      monitored, controlled, and optimized is to be achieved.

PMID- 17442881
TI  - Video technology to advance safety in the operating room and perioperative
      environment.
AB  - Video is a powerful medium and is underused for patient safety in several areas:
      education, real-time consultation, process improvement, research, and workflow
      coordination. We illustrate this point through an overview of uses of video in
      health care by the authors and others in several institutions. These uses were in
      the context of team work training, operating room coordination, technical skills
      of invasive procedures, process improvement, telementoring, and multimedia video
      records. Also described are several key issues associated with the use of video,
      such as ethics and legal concerns. Technology advances and new methods will make
      video an important tool for improving patient safety.

PMID- 17442882
TI  - Anatomy of a malpractice lawsuit.
AB  - Given the prevalence of medical malpractice lawsuits, physicians are often thrust
      into the legal world without the education of a juris doctor. The risk of facing
      suit varies among specialties, but there is no guarantee any physician will
      proceed through his or her career without being a defendant in a lawsuit. Every
      physician stands a significant chance of being sued. Although a lawsuit is an
      exhausting and intimidating situation in and of itself, the ramifications of a
      plaintiff's verdict could have chilling effects on the physician's life, both
      professionally and personally. Therefore, it is imperative that every physician
      have an understanding of the legal process of which he or she may become
      involved. This article provides a practical guide for the physician, including
      the fundamental procedures of a medical malpractice lawsuit, the behavior that
      will be expected or required of the defendant physician, and the effect of
      disobeying the required procedures.

PMID- 17442883
TI  - Making career choices.

PMID- 17442884
TI  - Gastrointestinal stromal tumors.

PMID- 17442886
TI  - Differential association of phosphatidylinositol 3-kinase, SHIP-1, and PTEN with
      forming phagosomes.
AB  - In macrophages, enzymes that synthesize or hydrolyze phosphatidylinositol (3,4,5)
      trisphosphate [PI(3,4,5)P(3)] regulate Fcgamma receptor-mediated phagocytosis.
      Inhibition of phosphatidylinositol 3-kinase (PI3K) or overexpression of the lipid
      phosphatases phosphatase and tensin homologue (PTEN) and Src homology 2 domain
      containing inositol phosphatase (SHIP-1), which hydrolyze PI(3,4,5)P(3) to
      phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4-bisphosphate
      [PI(3,4)P(2)], respectively, inhibit phagocytosis in macrophages. To examine how
      these enzymes regulate phagosome formation, the distributions of yellow
      fluorescent protein (YFP) chimeras of enzymes and pleckstrin homology (PH)
      domains specific for their substrates and products were analyzed quantitatively.
      PTEN-YFP did not localize to phagosomes, suggesting that PTEN regulates
      phagocytosis globally within the macrophage. SHIP1-YFP and p85-YFP were recruited
      to forming phagosomes. SHIP1-YFP sequestered to the leading edge and dissociated
      from phagocytic cups earlier than did p85-cyan fluorescent protein, indicating
      that SHIP-1 inhibitory activities are restricted to the early stages of
      phagocytosis. PH domain chimeras indicated that early during phagocytosis,
      PI(3,4,5)P(3) was slightly more abundant than PI(3,4)P(2) at the leading edge of
      the forming cup. These results support a model in which phagosomal PI3K generates
      PI(3,4,5)P(3) necessary for later stages of phagocytosis, PTEN determines whether
      those late stages can occur, and SHIP-1 regulates when and where they occur by
      transiently suppressing PI(3,4,5)P(3)-dependent activities necessary for
      completion of phagocytosis.

PMID- 17442887
TI  - MTOC reorientation occurs during FcgammaR-mediated phagocytosis in macrophages.
AB  - Cell polarization is essential for targeting signaling elements and organelles to
      active plasma membrane regions. In a few specialized cell types, cell polarity is
      enhanced by reorientation of the MTOC and associated organelles toward dynamic
      membrane sites. Phagocytosis is a highly polarized process whereby particles >0.5
      microm are internalized at stimulated regions on the cell surface of macrophages.
      Here we provide detailed evidence that the MTOC reorients toward the site of
      particle internalization during phagocytosis. We visualized MTOC proximity to IgG
      sRBCs in fixed RAW264.7 cells, during live cell imaging using fluorescent
      chimeras to label the MTOC and using frustrated phagocytosis assays. MTOC
      reorientation in macrophages is initiated by FcgammaR ligation and is complete
      within 1 h. Polarization of the MTOC toward the phagosome requires the MT
      cytoskeleton and dynein motor activity. cdc42, PI3K, and mPAR-6 are all important
      signaling molecules for MTOC reorientation during phagocytosis. MTOC
      reorientation was not essential for particle internalization or phagolysosome
      formation. However Golgi reorientation in concert with MTOC reorientation during
      phagocytosis implicates MTOC reorientation in antigen processing events in
      macrophages.

PMID- 17442888
TI  - Developmental and cell cycle regulation of the Drosophila histone locus body.
AB  - Cyclin E/Cdk2 is necessary for replication-dependent histone mRNA biosynthesis,
      but how it controls this process in early development is unknown. We show that in
      Drosophila embryos the MPM-2 monoclonal antibody, raised against a phosphoepitope
      from human mitotic cells, detects Cyclin E/Cdk2-dependent nuclear foci that
      colocalize with nascent histone transcripts. These foci are coincident with the
      histone locus body (HLB), a Cajal body-like nuclear structure associated with the
      histone locus and enriched in histone pre-mRNA processing factors such as Lsm11,
      a core component of the U7 small nuclear ribonucleoprotein. Using MPM-2 and anti
      Lsm11 antibodies, we demonstrate that the HLB is absent in the early embryo and
      occurs when zygotic histone transcription begins during nuclear cycle 11. Whereas
      the HLB is found in all cells after its formation, MPM-2 labels the HLB only in
      cells with active Cyclin E/Cdk2. MPM-2 and Lsm11 foci are present in embryos
      lacking the histone locus, and MPM-2 foci are present in U7 mutants, which cannot
      correctly process histone pre-mRNA. These data indicate that MPM-2 recognizes a
      Cdk2-regulated protein that assembles into the HLB independently of histone mRNA
      biosynthesis. HLB foci are present in histone deletion embryos, although the MPM
      2 foci are smaller, and some Lsm11 foci are not associated with MPM-2 foci,
      suggesting that the histone locus is important for HLB integrity.

PMID- 17442890
TI  - A Mutation in the SH2 domain of STAT2 prolongs tyrosine phosphorylation of STAT1
      and promotes type I IFN-induced apoptosis.
AB  - Type I interferons (IFN-alpha/beta) induce apoptosis in certain tumor cell lines
      but not others. Here we describe a mutation in STAT2 that confers an apoptotic
      effect in tumor cells in response to type I IFNs. This mutation was introduced in
      a conserved motif, PYTK, located in the STAT SH2 domain, which is shared by
      STAT1, STAT2, and STAT3. To test whether the tyrosine in this motif might be
      phosphorylated and affect signaling, Y631 of STAT2 was mutated to phenylalanine
      (Y631F). Although it was determined that Y631 was not phosphorylated, the Y631F
      mutation conferred sustained signaling and induction of IFN-stimulated genes.
      This prolonged IFN response was associated with sustained tyrosine
      phosphorylation of STAT1 and STAT2 and their mutual association as heterodimers,
      which resulted from resistance to dephosphorylation by the nuclear tyrosine
      phosphatase TcPTP. Finally, cells bearing the Y631F mutation in STAT2 underwent
      apoptosis after IFN-alpha stimulation compared with wild-type STAT2. Therefore,
      this mutation reveals that a prolonged response to IFN-alpha could account for
      one difference between tumor cell lines that undergo IFN-alpha-induced apoptosis
      compared with those that display an antiproliferative response but do not die.

PMID- 17442889
TI  - A cytosolic splice variant of Cab45 interacts with Munc18b and impacts on amylase
      secretion by pancreatic acini.
AB  - We identified in a yeast two-hybrid screen the EF-hand Ca(2+)-binding protein
      Cab45 as an interaction partner of Munc18b. Although the full-length Cab45
      resides in Golgi lumen, we characterize a cytosolic splice variant, Cab45b,
      expressed in pancreatic acini. Cab45b is shown to bind (45)Ca(2+), and, of its
      three EF-hand motifs, EF-hand 2 is demonstrated to be crucial for the ion
      binding. Cab45b is shown to interact with Munc18b in an in vitro assay, and this
      interaction is enhanced in the presence of Ca(2+). In this assay, Cab45b also
      binds the Munc18a isoform in a Ca(2+)-dependent manner. The endogenous Cab45b in
      rat acini coimmunoprecipitates with Munc18b, syntaxin 2, and syntaxin 3, soluble
      N-ethylmaleimide-sensitive factor attachment protein receptors with key roles in
      the Ca(2+)-triggered zymogen secretion. Furthermore, we show that Munc18b bound
      to syntaxin 3 recruits Cab45b onto the plasma membrane. Importantly, antibodies
      against Cab45b are shown to inhibit in a specific and dose-dependent manner the
      Ca(2+)-induced amylase release from streptolysin-O-permeabilized acini. The
      present study identifies Cab45b as a novel protein factor involved in the
      exocytosis of zymogens by pancreatic acini.

PMID- 17442891
TI  - Ihh/Gli2 signaling promotes osteoblast differentiation by regulating Runx2
      expression and function.
AB  - Genetic and cell biological studies have indicated that Indian hedgehog (Ihh)
      plays an important role in bone development and osteoblast differentiation.
      However, the molecular mechanism by which Ihh regulates osteoblast
      differentiation is complex and remains to be fully elucidated. In this study, we
      investigated the role of Ihh signaling in osteoblast differentiation using
      mesenchymal cells and primary osteoblasts. We observed that Ihh stimulated
      alkaline phosphatase (ALP) activity, osteocalcin expression, and calcification.
      Overexpression of Gli2- but not Gli3-induced ALP, osteocalcin expression, and
      calcification of these cells. In contrast, dominant-negative Gli2 markedly
      inhibited Ihh-dependent osteoblast differentiation. Ihh treatment or Gli2
      overexpression also up-regulated the expression of Runx2, an essential
      transcription factor for osteoblastogenesis, and enhanced the transcriptional
      activity and osteogenic action of Runx2. Coimmunoprecipitation analysis
      demonstrated a physical interaction between Gli2 and Runx2. Moreover, Ihh or Gli2
      overexpression failed to increase ALP activity in Runx2-deficient mesenchymal
      cells. Collectively, these results suggest that Ihh regulates osteoblast
      differentiation of mesenchymal cells through up-regulation of the expression and
      function of Runx2 by Gli2.

PMID- 17442893
TI  - Summary of the American Heart Association's scientific statement on drug therapy
      of high-risk lipid abnormalities in children and adolescents.

PMID- 17442892
TI  - The conserved Spc7 protein is required for spindle integrity and links
      kinetochore complexes in fission yeast.
AB  - Spc7, a member of the conserved Spc105/KNL-1 family of kinetochore proteins, was
      identified as an interaction partner of the EB1 homologue Mal3. Spc7 associates
      with the central centromere region of the chromosome but does not affect
      transcriptional silencing. Here, we show that Spc7 is required for the integrity
      of the spindle as well as for targeting of MIND but not of Ndc80 complex
      components to the kinetochore. Spindle defects in spc7 mutants were severe
      ranging from the inability to form a bipolar spindle in early mitosis to broken
      spindles in midanaphase B. spc7 mutant phenotypes were partially rescued by extra
      alpha-tubulin or extra Mal2. Thus, Spc7 interacts genetically with the Mal2
      containing Sim4 complex.

PMID- 17442894
TI  - Is pathologic intimal thickening the key to understanding early plaque
      progression in human atherosclerotic disease?

PMID- 17442895
TI  - Inflammatory blues turns velvet skin into rawhide: monocyte rolling on modified
      endothelial PSGL-1.

PMID- 17442896
TI  - Choking off plaque neovascularity: a promising atheroprotective strategy or a
      double-edged sword?

PMID- 17442897
TI  - Hydrogen peroxide derived from beating heart mediates coronary microvascular
      dilation during tachycardia.
AB  - OBJECTIVE: Coronary flow is closely correlated to the myocardial metabolic
      demand. We tested the hypothesis that hydrogen peroxide (H2O2) derived from
      beating hearts mediates metabolic coronary microvascular dilation. METHODS AND
      RESULTS: We used a bioassay method in which an isolated microvessel is placed on
      a beating heart to detect myocardium-derived vasoactive mediators. A rabbit
      coronary arterial microvessel (detector vessel [DV], n=25) was pressurized and
      placed on a canine beating heart. After intrinsic tone of DV had developed, we
      observed DV at rest (heart rate, 120 bpm) and during tachypacing (heart rate, 240
      bpm) using an intravital microscope equipped with a floating objective. The
      tachypacing produced DV dilation by 8.2% (P<0.01 versus baseline), and the
      dilation was abolished by cell-impermeable catalase (a H2O2 scavenger, 500 U/mL).
      We performed myocardial biopsy at rest and tachypacing. The biopsy specimens were
      loaded with 2',7'-dichlorodihydrofluorescein diacetate (10 micromol/L) to
      visualize H2O2, and observed with confocal microscopy. Dichlorofluorescein
      fluorescence was diffusely identified in the myocardium and the tachypacing
      increased the fluorescence intensity (P<0.01). Exogenous H2O2 caused vasodilation
      of arterial microvessels in vitro in a concentration-dependent manner that was
      abolished by catalase. CONCLUSIONS: H2O2 derived from the beating heart mediates
      tachypacing-induced metabolic coronary vasodilation in vivo.

PMID- 17442900
TI  - Gender differences in coronary arteries and thoracic aorta calcification.

PMID- 17442899
TI  - Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes
      atherosclerosis.
AB  - OBJECTIVE: Mechanisms by which tumor necrosis factor-alpha (TNF) contributes to
      atherosclerosis remain largely obscure. We therefore sought to determine the role
      of the arterial wall TNF receptor-1 (TNFR1) in atherogenesis. METHODS AND
      RESULTS: Carotid artery-to-carotid artery interposition grafting was performed
      with tnfr1-/- and congenic (C57Bl/6) wild-type (WT) mice as graft donors, and
      congenic chow-fed apolipoprotein E-deficient mice as recipients. Advanced
      atherosclerotic graft lesions developed within 8 weeks, and had 2-fold greater
      area in WT than in tnfr1-/- grafts. While the prevalence of specific atheroma
      cells was equivalent in WT and tnfr1-/- grafts, the overall abundance of cells
      was substantially greater in WT grafts. WT grafts demonstrated greater MCP-1,
      vascular cell adhesion molecule-1, and intercellular adhesion molecule-1
      expression at both early and late time points, and proliferating cell nuclear
      antigen expression at early time points. Aortic atherosclerosis was also reduced
      in 14-month-old apoe(-/-)/tnfr1(-/-) mice, as compared with cognate apoe-/- mice.
      In coculture with activated macrophages, smooth muscle cells expressing the TNFR1
      demonstrated enhanced migration and reduced scavenger receptor activity.
      CONCLUSIONS: TNFR1 signaling, just in arterial wall cells, contributes to the
      pathogenesis of atherosclerosis by enhancing arterial wall chemokine and adhesion
      molecule expression, as well as by augmenting medial smooth muscle cell
      proliferation and migration.

PMID- 17442901
TI  - Images in clinical medicine. Meningioma.

PMID- 17442902
TI  - The FDA and the case of Ketek.

PMID- 17442903
TI  - Approving the vagus-nerve stimulator for depression.

PMID- 17442904
TI  - Transfusion strategies for patients in pediatric intensive care units.
AB  - BACKGROUND: The optimal hemoglobin threshold for erythrocyte transfusions in
      critically ill children is unknown. We hypothesized that a restrictive
      transfusion strategy of using packed red cells that were leukocyte-reduced before
      storage would be as safe as a liberal transfusion strategy, as judged by the
      outcome of multiple-organ dysfunction. METHODS: In this noninferiority trial, we
      enrolled 637 stable, critically ill children who had hemoglobin concentrations
      below 9.5 g per deciliter within 7 days after admission to an intensive care
      unit. We randomly assigned 320 patients to a hemoglobin threshold of 7 g per
      deciliter for red-cell transfusion (restrictive-strategy group) and 317 patients
      to a threshold of 9.5 g per deciliter (liberal-strategy group). RESULTS:
      Hemoglobin concentrations were maintained at a mean (+/-SD) level that was 2.1+/
      0.2 g per deciliter lower in the restrictive-strategy group than in the liberal
      strategy group (lowest average levels, 8.7+/-0.4 and 10.8+/-0.5 g per deciliter,
      respectively; P<0.001). Patients in the restrictive-strategy group received 44%
      fewer transfusions; 174 patients (54%) in that group did not receive any
      transfusions, as compared with 7 patients (2%) in the liberal-strategy group
      (P<0.001). New or progressive multiple-organ dysfunction syndrome (the primary
      outcome) developed in 38 patients in the restrictive-strategy group, as compared
      with 39 in the liberal-strategy group (12% in both groups) (absolute risk
      reduction with the restrictive strategy, 0.4%; 95% confidence interval, -4.6 to
      5.4). There were 14 deaths in each group within 28 days after randomization. No
      significant differences were found in other outcomes, including adverse events.
      CONCLUSIONS: In stable, critically ill children a hemoglobin threshold of 7 g per
      deciliter for red-cell transfusion can decrease transfusion requirements without
      increasing adverse outcomes. (Controlled-trials.com number, ISRCTN37246456
      [controlled-trials.com].).

PMID- 17442906
TI  - Targeted therapy for inherited GPI deficiency.
AB  - Disrupted binding of the transcription factor Sp1 to the mutated promoter region
      of the mannosyl transferase-encoding gene PIGM causes inherited
      glycosylphosphatidylinositol (GPI) deficiency characterized by splanchnic vein
      thrombosis and epilepsy. We show that this results in histone hypoacetylation at
      the promoter of PIGM. The histone deacetylase inhibitor butyrate increases PIGM
      transcription and surface GPI expression in vitro as well as in vivo through
      enhanced histone acetylation in an Sp1-dependent manner. More important, the drug
      caused complete cessation of intractable seizures in a child with inherited GPI
      deficiency.

PMID- 17442905
TI  - Omeprazole before endoscopy in patients with gastrointestinal bleeding.
AB  - BACKGROUND: A neutral gastric pH is critical for the stability of clots over
      bleeding arteries. We investigated the effect of preemptive infusion of
      omeprazole before endoscopy on the need for endoscopic therapy. METHODS:
      Consecutive patients admitted with upper gastrointestinal bleeding underwent
      stabilization and were then randomly assigned to receive either omeprazole or
      placebo (each as an 80-mg intravenous bolus followed by an 8-mg infusion per
      hour) before endoscopy the next morning. RESULTS: Over a 17-month period, 638
      patients were enrolled and randomly assigned to omeprazole or placebo (319 in
      each group). The need for endoscopic treatment was lower in the omeprazole group
      than in the placebo group (60 of the 314 patients included in the analysis
      [19.1%] vs. 90 of 317 patients [28.4%], P=0.007). There were no significant
      differences between the omeprazole group and the placebo group in the mean amount
      of blood transfused (1.54 and 1.88 units, respectively; P=0.12) or the number of
      patients who had recurrent bleeding (11 and 8, P=0.49), who underwent emergency
      surgery (3 and 4, P=1.00), or who died within 30 days (8 and 7, P=0.78). The
      hospital stay was less than 3 days in 60.5% of patients in the omeprazole group,
      as compared with 49.2% in the placebo group (P=0.005). On endoscopy, fewer
      patients in the omeprazole group had actively bleeding ulcers (12 of 187, vs. 28
      of 190 in the placebo group; P=0.01) and more omeprazole-treated patients had
      ulcers with clean bases (120 vs. 90, P=0.001). CONCLUSIONS: Infusion of high-dose
      omeprazole before endoscopy accelerated the resolution of signs of bleeding in
      ulcers and reduced the need for endoscopic therapy. (ClinicalTrials.gov number,
      NCT00164866 [ClinicalTrials.gov] .).

PMID- 17442907
TI  - Clinical practice. Fecal incontinence in adults.

PMID- 17442908
TI  - Images in clinical medicine. Intestinal obstruction due to inspissated barium.

PMID- 17442909
TI  - Case records of the Massachusetts General Hospital. Case 12-2007. A 56-year-old
      woman with renal failure after heart-lung transplantation.

PMID- 17442910
TI  - Blood transfusion--when is more really less?

PMID- 17442911
TI  - The decrease in breast-cancer incidence in 2003 in the United States.
AB  - An initial analysis of data from the National Cancer Institute's Surveillance,
      Epidemiology, and End Results (SEER) registries shows that the age-adjusted
      incidence rate of breast cancer in women in the United States fell sharply (by
      6.7%) in 2003, as compared with the rate in 2002. Data from 2004 showed a
      leveling off relative to the 2003 rate, with little additional decrease.
      Regression analysis showed that the decrease began in mid-2002 and had begun to
      level off by mid-2003. A comparison of incidence rates in 2001 with those in 2004
      (omitting the years in which the incidence was changing) showed that the decrease
      in annual age-adjusted incidence was 8.6% (95% confidence interval [CI], 6.8 to
      10.4). The decrease was evident only in women who were 50 years of age or older
      and was more evident in cancers that were estrogen-receptor-positive than in
      those that were estrogen-receptor-negative. The decrease in breast-cancer
      incidence seems to be temporally related to the first report of the Women's
      Health Initiative and the ensuing drop in the use of hormone-replacement therapy
      among postmenopausal women in the United States. The contributions of other
      causes to the change in incidence seem less likely to have played a major role
      but have not been excluded.

PMID- 17442912
TI  - Ketek--the FDA perspective.

PMID- 17442913
TI  - Dopamine agonists and valvular heart disease.

PMID- 17442914
TI  - Long-QT syndrome.

PMID- 17442915
TI  - Persistent coronary occlusion after myocardial infarction.

PMID- 17442916
TI  - Antibiotic prophylaxis in colorectal surgery.

PMID- 17442917
TI  - International aeromedical evacuation.

PMID- 17442918
TI  - Recombinant PTH for initial management of neonatal hypocalcemia.

PMID- 17442919
TI  - Cloning IL-1 and the birth of a new era in cytokine biology.

PMID- 17442920
TI  - Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc. Natl.
      Acad. Sci. USA 1984. 81: 7907-7911.

PMID- 17442921
TI  - Clinical transplantation tolerance: many rivers to cross.
AB  - Modern immunosuppressive regimens for organ transplantation have resulted in
      excellent short-term results but less dramatic improvements in long-term
      outcomes. Moreover, they are associated with significant deleterious effects. One
      solution that should avoid the adverse drug effects and result in improved graft
      and patient longevity as well as positively impacting on the organ shortage is
      the establishment of transplantation tolerance. Ever since the original
      description of transplantation tolerance in rodent allografts, there have been
      significant efforts made to translate tolerance-promoting strategies to the
      clinical arena. However, >50 years later, we are still faced with significant
      barriers that are preventing such a goal from being widely attained. Nonetheless,
      pilot clinical tolerance protocols are underway in selected transplant
      recipients. In this review, we discuss the scientific and nonscientific issues
      that must be overcome for successful transplantation tolerance to become a
      clinical reality.

PMID- 17442922
TI  - Cutting edge: Alternative signaling of Th17 cell development by sphingosine 1
      phosphate.
AB  - Sphingosine 1-phosphate (S1P) in blood and lymph controls T cell traffic and
      proliferation through type 1 S1P receptor (S1P(1)) signals, but suppression of
      IFN-gamma generation has been the only consistently observed effect on T cell
      cytokines. The fact that S1P enhances the development of Th17 cells from Ag
      challenged transgenic S1P(1)-overexpressing CD4 T cells suggested that the S1P
      S1P(1) axis may promote the expansion of Th17 cells in wild-type mice. In a model
      of Th17 cell development from CD4 T cells stimulated by anti-CD3 plus anti-CD28
      Abs and a mixture of TGF-beta1, IL-1, and IL-6, S1P enhanced their number and IL
      17-generating activity the same as IL-23. As for IL-23 enhancement of Th17 cell
      development, that by S1P was prevented by IL-4 plus IFN-gamma and by IL-27. The
      prevention of S1P augmentation of Th17 cell development by the S1P receptor
      agonist and down-regulator FTY720 implies that FTY720 immunosuppression is
      attributable partially to inhibition of Th17-mediated inflammation.

PMID- 17442923
TI  - Cutting edge: Lipopolysaccharide induces IL-10-producing regulatory CD4+ T cells
      that suppress the CD8+ T cell response.
AB  - TLR ligands are potent activators of dendritic cells and therefore function as
      adjuvants for the induction of immune responses. We analyzed the capacity of TLR
      ligands to enhance CD8+ T cell responses toward soluble protein Ag. Immunization
      with OVA together with LPS or poly(I:C) elicited weak CD8+ T cell responses in
      wild-type C57BL/6 mice. Surprisingly, these responses were greatly increased in
      mice lacking CD4+ T cells indicating the induction of regulatory CD4+ T cells. In
      vivo, neutralization of IL-10 completely restored CD8+ T cell responses in wild
      type mice and OVA-specific IL-10 producing CD4+ T cells were detected after
      immunization with OVA plus LPS. Our study shows that TLR ligands not only
      activate the immune system but simultaneously induce Ag specific, IL-10-producing
      regulatory Tr1 cells that strongly suppress CD8+ T cell responses. In this way,
      excessive activation of the immune system may be prevented.

PMID- 17442924
TI  - The Pro-Th1 cytokine IL-12 enhances IL-4 production by invariant NKT cells:
      relevance for T cell-mediated hepatitis.
AB  - IL-12 is essential for invariant NKT (iNKT) cells because it can maintain a
      functionally active population and promote a cytokine profile that is assumed to
      be mainly of the pro-Th1 type. We used the murine concanavalin A (Con A)-induced
      hepatitis model, in which iNKT cells, IL-12, IL-4, and IFN-gamma are equally
      requisite, to reevaluate this issue. We demonstrate that IL-12 interacts directly
      with iNKT cells, contributes to their recruitment to the liver, and enhances
      their IL-4 production, which is essential for disease onset. IL-12-deficient mice
      were less susceptible to experimental hepatitis and their iNKT cells produced
      less IL-4 than their wild-type counterpart. A normal response could be restored
      by IL-12 injection, revealing its importance as endogenous mediator. In
      accordance with this observation, we found that iNKT cells expressed the IL-12R
      constitutively, in contrast to conventional T cells. Furthermore, the
      physiological relevance of our data is supported by the lower susceptibility to
      disease induction of NOD mice, known for their inherent functional and numerical
      abnormalities of iNKT cells associated with decreased iNKT cell-derived IL-4
      production and low IL-12 secretion. Taken together, our findings provide the
      first evidence that IL-12 can enhance the immune response through increased IL-4
      production by iNKT cells, underscoring once more the functional plasticity of
      this subset.

PMID- 17442925
TI  - Unequal contribution of Akt isoforms in the double-negative to double-positive
      thymocyte transition.
AB  - Pre-TCR signals regulate the transition of the double-negative (DN) 3 thymocytes
      to the DN4, and subsequently to the double-positive (DP) stage. In this study, we
      show that pre-TCR signals activate Akt and that pharmacological inhibition of the
      PI3K/Akt pathway, or combined ablation of Akt1 and Akt2, and to a lesser extent
      Akt1 and Akt3, interfere with the differentiation of DN3 and the accumulation of
      DP thymocytes. Combined ablation of Akt1 and Akt2 inhibits the proliferation of
      DN4 cells, while combined ablation of all Akt isoforms also inhibits the survival
      of all the DN thymocytes. Finally, the combined ablation of Akt1 and Akt2
      inhibits the survival of DP thymocytes. Constitutively active Lck-Akt1 transgenes
      had the opposite effects. We conclude that, following their activation by pre-TCR
      signals, Akt1, Akt2, and, to a lesser extent, Akt3 promote the transition of DN
      thymocytes to the DP stage, in part by enhancing the proliferation and survival
      of cells undergoing beta-selection. Akt1 and Akt2 also contribute to the
      differentiation process by promoting the survival of the DP thymocytes.

PMID- 17442926
TI  - CD83 knockdown in monocyte-derived dendritic cells by small interfering RNA leads
      to a diminished T cell stimulation.
AB  - Mature human dendritic cells (mDCs) are the most powerful APCs known today,
      having the unique ability to induce primary immune responses. One of the best
      known surface markers for mDCs is the glycoprotein CD83, which is strongly up
      regulated during maturation, together with costimulatory molecules such as CD80
      and CD86. When CD83 surface expression was inhibited by interference with the
      messenger RNA export or by infection with certain viruses, DCs showed a
      dramatically reduced capability to induce T cell proliferation. However, in these
      cases side effects on other cellular functions cannot be excluded completely. In
      this study we present an efficient method to specifically influence CD83 surface
      expression by the use of RNA interference. We used small-interfering RNA targeted
      against CD83 and carefully evaluated an electroporation protocol for the delivery
      of the duplex into the cells. Furthermore, we identified freshly prepared
      immature DCs as the best target for the application of a CD83 knockdown and we
      were also able to achieve a long lasting silencing effect for this molecule.
      Finally, we were able to confirm that CD83 functions as an enhancer during the
      stimulation of T cells, significantly increases DC-mediated T cell proliferation,
      and goes hand in hand with clear changes in cytokine expression during T cell
      priming. These results were obtained for the first time without the use of agents
      that might cause unwanted side effects, such as low m.w. inhibitors or viruses.
      Therefore, this method presents a suitable way to influence DC biology.

PMID- 17442927
TI  - Human CD4+ T cells displaying viral epitopes elicit a functional virus-specific
      memory CD8+ T cell response.
AB  - The Ag-specific cellular recall response to herpes virus infections is
      characterized by a swift recruitment of virus-specific memory T cells. Rapid
      activation is achieved through formation of the immunological synapse and
      supramolecular clustering of signal molecules at the site of contact. During the
      formation of the immunological synapse, epitope-loaded MHC molecules are
      transferred via trogocytosis from APCs to T cells, enabling the latter to
      function as Ag-presenting T cells (T-APCs). The contribution of viral epitope
      expressing T-APCs in the regulation of the herpes virus-specific CD8+ T cell
      memory response remains unclear. Comparison of CD4+ T-APCs with professional APCs
      such as Ag-presenting CD40L-activated B cells (CD40B-APCs) demonstrated reduced
      levels of costimulatory ligands. Despite the observed differences, CD4+ T-APCs
      are as potent as CD40B-APCs in stimulating herpes virus-specific CD8+ T cells
      resulting in a greater than 35-fold expansion of CD8+ T cells specific for
      dominant and subdominant viral epitopes. Virus-specific CD8+ T cells generated by
      CD4+ T-APCs or CD40B-APCs showed both comparable effector function such as
      specific lysis of targets and cytokine production and also did not differ in
      their phenotype after expansion. These results indicate that viral epitope
      presentation by Ag-specific CD4+ T cells may contribute to the rapid recruitment
      of virus-specific memory CD8+ T cells during a viral recall response.

PMID- 17442928
TI  - Down-regulation of IL-7Ralpha expression in human T cells via DNA methylation.
AB  - IL-7 is critical for the development and survival of T cells. Recently, we found
      two subsets of human CD8+ T cells expressing IL-7Ralpha(high) and IL-7Ralpha(low)
      with different cell survival responses to IL-7. Although these CD8+ T cell
      subsets have differential IL-7Ralpha gene expression, the mechanism for this is
      unknown. DNA methylation is an important gene regulatory mechanism and is
      associated with the inactivation of gene expression. Thus, we investigated a role
      for DNA methylation in differentially regulating IL-7Ralpha gene expression in
      human CD8+ T cells and Jurkat T cells. IL-7Ralpha(high)CD8+ T cells had decreased
      methylation in the IL-7Ralpha gene promoter compared with IL-7Ralpha(low)CD8+ T
      cells and Jurkat T cells with low levels of IL-7Ralpha. Treating Jurkat T cells
      with 5-aza-2'-deoxycytidine, which reduced DNA methylation, increased IL-7Ralpha
      expression. Plus, the unmethylated IL-7Ralpha gene promoter construct had higher
      levels of promoter activity than the methylated one as measured by a luciferase
      reporter assay. These findings suggest that DNA methylation is involved in
      regulating IL-7Ralpha expression in T cells via affecting IL-7Ralpha gene
      promoter activity, and that the methylation of this gene promoter could be a
      potential target for modifying IL-7-mediated T cell development and survival.

PMID- 17442929
TI  - Immune modulation and tolerance induction by RelB-silenced dendritic cells
      through RNA interference.
AB  - Dendritic cells (DC), the most potent APCs, can initiate the immune response or
      help induce immune tolerance, depending upon their level of maturation. DC
      maturation is associated with activation of the NF-kappaB pathway, and the
      primary NF-kappaB protein involved in DC maturation is RelB, which coordinates
      RelA/p50-mediated DC differentiation. In this study, we show that silencing RelB
      using small interfering RNA results in arrest of DC maturation with reduced
      expression of the MHC class II, CD80, and CD86. Functionally, RelB-silenced DC
      inhibited MLR, and inhibitory effects on alloreactive immune responses were in an
      Ag-specific fashion. RelB-silenced DC also displayed strong in vivo immune
      regulation. An inhibited Ag-specific response was seen after immunization with
      keyhole limpet hemocyanin-pulsed and RelB-silenced DC, due to the expansion of T
      regulatory cells. Administration of donor-derived RelB-silenced DC significantly
      prevented allograft rejection in murine heart transplantation. This study
      demonstrates for the first time that transplant tolerance can be induced by means
      of RNA interference using in vitro-generated tolerogenic DC.

PMID- 17442930
TI  - Noncognate interaction with MHC class II molecules is essential for maintenance
      of T cell metabolism to establish optimal memory CD4 T cell function.
AB  - CD4 memory T cells surviving in the absence of MHC class II contact lose their
      characteristic memory function. To investigate the mechanisms underlying the
      impaired function of memory T cells in the absence of MHC class II molecules, we
      analyzed gene expression profiles of resting memory T cells isolated from MHC
      class II-competent or -deficient hosts. The analysis focused on five transcripts
      related to T cell activation, metabolism, and survival that are underexpressed in
      resting memory T cells from MHC class II-deficient hosts compared with MHC class
      II-competent hosts. CD4 memory cells isolated from MHC class II-deficient hosts
      display alterations in their degree of differentiation as well as metabolic
      activity, and these changes are already manifest in the effector phase despite
      the presence of Ag-expressing dendritic cells. Our data suggest that the absence
      of interactions with noncognate MHC class II molecules compromises the
      progressive accumulation of signals that ensure optimal survival and fitness to
      sustain the metabolic activity of activated T cells and shape the functional
      capacity of the future memory compartment. Signals via AKT coordinate survival
      and metabolic pathways and may be one of the crucial events linking interaction
      with MHC class II molecules to the successful generation of a long-lived
      functional memory CD4 T cell population.

PMID- 17442931
TI  - Kruppel-like transcription factor 13 regulates T lymphocyte survival in vivo.
AB  - Kruppel-like transcription factor (KLF)13, previously shown to regulate RANTES
      expression in vitro, is a member of the Kruppel- like family of transcription
      factors that controls many growth and developmental processes. To ascertain the
      function of KLF13 in vivo, Klf13-deficient mice were generated by gene targeting.
      As expected, activated T lymphocytes from Klf13(-/-) mice show decreased RANTES
      expression. However, these mice also exhibit enlarged thymi and spleens. TUNEL,
      as well as spontaneous and activation-induced death assays, demonstrated that
      prolonged survival of Klf13(-/-) thymocytes was due to decreased apoptosis.
      Microarray analysis suggests that protection from apoptosis-inducing stimuli in
      Klf13(-/-) thymocytes is due in part to increased expression of BCL-X(L), a
      potent antiapoptotic factor. This finding was confirmed in splenocytes and total
      thymocytes by real-time quantitative PCR and Western blot as well as in CD4+CD8-
      single-positive thymocytes by real-time quantitative PCR. Furthermore, EMSA and
      luciferase reporter assays demonstrated that KLF13 binds to multiple sites within
      the Bcl-X(L) promoter and results in decreased Bcl-X(L) promoter activity, making
      KLF13 a negative regulator of BCL-X(L).

PMID- 17442932
TI  - Characterizing T cell movement within lymph nodes in the absence of antigen.
AB  - The recent application of two-photon microscopy to the visualization of T cell
      movement has presented trajectories of individual T cells within lymphoid organs
      both in the presence and in the absence of Ag-loaded dendritic cells. Remarkably,
      even though T cells largely move along conduits of the fibroblastic reticular
      cell network, they appear to execute random walks in lymphoid organs rather than
      chemotaxis. In this study, we analyze experimental trajectories of T cells using
      computer simulations of idealized random walks. Comparisons of simulations with
      experimental data provide estimates of key parameters that characterize T cell
      motion in vivo. For example, we find that the distance moved before turning is
      about twice the distance between intersections in the fibroblastic reticular cell
      network, suggesting that at an intersection a T cell will turn onto a new fiber
      approximately 50% of the time. Although the calibrated model appears to offer an
      accurate representation of T cell movement, it has also uncovered inconsistencies
      across different experimental data sets.

PMID- 17442933
TI  - Altering effects of antigenic variations in HIV-1 on antiviral effectiveness of
      HIV-specific CTLs.
AB  - The mutational escape of HIV-1 from established CTL responses is becoming
      evident. However, it is not yet clear whether antigenic variations of HIV-1 may
      have an additional effect on the differential antiviral effectiveness of HIV
      specific CTLs. Herein, we characterized HIV-specific CTL responses toward Pol,
      Env, and Nef optimal epitopes presented by HLA-B*35 during a chronic phase of HIV
      1 infection. We found CTL escape variants within Pol and Nef epitopes that
      affected recognition by TCRs, although there was no mutation within the Env
      epitope. An analysis of peptide-HLA tetrameric complexes revealed that CD8 T
      cells exclusively specific for the Nef variant were generated following
      domination by the variant viruses. The variant-specific cells were capable of
      killing target cells and producing antiviral cytokines but showed impaired Ag
      specific proliferation ex vivo, whereas wild-type specific cells had potent
      activities. Moreover, clonotypic CD8 T cells specific for the Pol variant showed
      diminished proliferation, whereas Env-specific ones had no functional
      heterogeneity. Taken together, our data indicate that antigenic variations that
      abolished TCR recognition not only resulted in escape from established CTL
      responses but also eventually generated another subset of variant-specific CTLs
      having decreased antiviral activity, causing an additional negative effect on
      antiviral immune responses during a chronic HIV infection.

PMID- 17442934
TI  - CD56 marks an effector T cell subset in the human intestine.
AB  - T cells are key mediators of intestinal immunity, and specific T cell subsets can
      have differing immunoregulatory roles in animal models of mucosal inflammation.
      In this study, we describe human CD56+ T cells as a morphologically distinct
      population expressing a mature, nonproliferative phenotype that is frequent in
      the gut. Enhanced potential for IFN-gamma and TNF synthesis suggested a
      proinflammatory function, and we directly demonstrate effector function mediated
      by direct T-T interaction with responder cells in vitro. CD56+ T cells from
      peripheral blood responded to the gut-related CD2 signal, and were necessary for
      effective CD2-mediated proliferation of peripheral blood CD56- T cells. Our
      findings associate CD56+ T cells with the intestinal immune compartment and
      suggest a putative effector function in human mucosal immunity.

PMID- 17442935
TI  - Sulfamethoxazole and its metabolite nitroso sulfamethoxazole stimulate dendritic
      cell costimulatory signaling.
AB  - Different signals in addition to the antigenic signal are required to initiate an
      immunological reaction. In the context of sulfamethoxazole allergy, the Ag is
      thought to be derived from its toxic nitroso metabolite, but little is known
      about the costimulatory signals, including those associated with dendritic cell
      maturation. In this study, we demonstrate increased CD40 expression, but not
      CD80, CD83, or CD86, with dendritic cell surfaces exposed to sulfamethoxazole
      (250-500 microM) and the protein-reactive metabolite nitroso sulfamethoxazole (1
      10 microM). Increased CD40 expression was not associated with apoptosis or
      necrosis, or glutathione depletion. Covalently modified intracellular proteins
      were detected when sulfamethoxazole was incubated with dendritic cells.
      Importantly, the enzyme inhibitor 1-aminobenzotriazole prevented the increase in
      CD40 expression with sulfamethoxazole, but not with nitroso sulfamethoxazole or
      LPS. The enzymes CYP2C9, CYP2C8, and myeloperoxidase catalyzed the conversion of
      sulfamethoxazole to sulfamethoxazole hydroxylamine. Myeloperoxidase was expressed
      at high levels in dendritic cells. Nitroso sulfamethoxazole immunogenicity was
      inhibited in mice with a blocking anti-CD40L Ab. In addition, when a primary
      nitroso sulfamethoxazole-specific T cell response using drug-naive human cells
      was generated, the magnitude of the response was enhanced when cultures were
      exposed to a stimulatory anti-CD40 Ab. Finally, increased CD40 expression was 5
      fold higher on nitroso sulfamethoxazole-treated dendritic cells from an HIV
      positive allergic patient compared with volunteers. These data provide evidence
      of a link between localized metabolism, dendritic cell activation, and drug
      immunogenicity.

PMID- 17442936
TI  - CTLA-4 differentially regulates the immunological synapse in CD4 T cell subsets.
AB  - Primary murine Th1 and Th2 cells differ in the organization of the immunological
      synapse, with Th1 cells, but not Th2 cells, clustering signaling molecules at the
      T cell/B cell synapse site. We sought to determine whether differential
      costimulatory signals could account for the differences observed. We found that
      Th2 cells express higher levels of CTLA-4 than Th1 cells, and demonstrated that
      Th2 cells lacking CTLA-4 are now able to cluster the TCR with the same frequency
      as Th1 cells. Furthermore, reconstitution of CTLA-4 into CTLA-4-deficient Th2
      cells, or into Th1 cells, inhibits the clustering of the TCR. We have also shown
      that Th2 cells, but not Th1 cells, show variations in the organization of the
      immunological synapse depending on levels of expression of CD80/CD86 on the APC.
      These studies demonstrate a unique role for CTLA-4 as a critical regulator of Th2
      cells and the immunological synapse.

PMID- 17442937
TI  - Characterization of human lung tumor-associated fibroblasts and their ability to
      modulate the activation of tumor-associated T cells.
AB  - The tumor microenvironment of human non-small cell lung cancer (NSCLC) is
      composed largely of stromal cells, including fibroblasts, yet these cells have
      been the focus of few studies. In this study, we established stromal cell
      cultures from primary NSCLC through isolation of adherent cells. Characterization
      of these cells by flow cytometry demonstrated a population which expressed a
      human fibroblast-specific 112-kDa surface molecule, Thy1, alpha-smooth muscle
      actin, and fibroblast activation protein, but failed to express CD45 and CD11b, a
      phenotype consistent with that of an activated myofibroblast. A subset of the
      tumor-associated fibroblasts (TAF) was found to express B7H1 (PD-L1) and B7DC (PD
      L2) constitutively, and this expression was up-regulated by IFN-gamma. Production
      of cytokines and chemokines, including IFN-gamma, monokine induced by IFN-gamma,
      IFN-gamma-inducible protein-10, RANTES, and TGF-beta1 was also demonstrated in
      these cells. Together, these characteristics provide multiple opportunities for
      the TAF to influence cellular interactions within the tumor microenvironment. To
      evaluate the ability of TAF to modulate tumor-associated T cell (TAT) activation,
      we conducted coculture experiments between autologous TAF and TAT. In five of
      eight tumors, TAF elicited a contact-dependent enhancement of TAT activation,
      even in the presence of a TGF-beta1-mediated suppressive effect. In the three
      other tumors, TAF had a net suppressive effect upon TAT activation, and, in one
      of these cases, blockade of B7H1 or B7DC was able to completely abrogate the TAF
      mediated suppression. We conclude that TAF in human NSCLC are functionally and
      phenotypically heterogeneous and provide multiple complex regulatory signals that
      have the potential to enhance or suppress TAT function in the tumor
      microenvironment.

PMID- 17442938
TI  - Paradoxical effect of reduced costimulation in T cell-mediated colitis.
AB  - B7-1 and B7-2 play different roles in the pathogenesis of autoimmunity, but this
      is controversial. We analyzed colitis induced by transfer of CD45RB(high)CD4(+) T
      cells to RAG(-/-) recipients lacking B7-1 and/or B7-2. Surprisingly, disease was
      greatly accelerated in RAG(-/-) recipients deficient for either B7-1 or B7-2,
      especially in the B7-2(-/-) recipients. This accelerated colitis induction
      correlated with increased T cell division in vivo and production of Th1
      cytokines. Although colitis pathogenesis following T cell transfer was inhibited
      in the absence of CD40L expression, CD40-CD40L interactions were not required in
      the B7-2(-/-) RAG(-/-) recipients. In vitro priming by APCs lacking either B7-1
      or B7-2 caused decreased IL-2 production, which led to decreased CTLA-4
      expression, although T cells primed in this way could respond vigorously upon
      restimulation by producing increased IL-2 and proinflammatory cytokines.
      Consistent with this mechanism, we demonstrate that blocking IL-2 early after T
      cell transfer accelerated colitis. Our data therefore outline a mechanism whereby
      synergistic costimulation by B7-1 and B7-2 molecules during priming is required
      for optimal IL-2 production. The consequent inhibitory effect of full CTLA-4
      expression, induced by IL-2, may slow colitis, even in the absence of regulatory
      T cells.

PMID- 17442939
TI  - Skin-infiltrating CD8+ T cells initiate atopic dermatitis lesions.
AB  - Skin lesions in the allergic form of atopic dermatitis (AD) are induced by
      allergen-specific T cells that infiltrate the skin at the site of allergen
      exposure. Although Th2-type CD4+ T cells appear to be crucial in AD
      pathophysiology, little is known about the contribution of CD8+ T cells in the
      development of the allergic skin inflammation. In the present study, we have
      analyzed the respective role of CD8+ and CD4+ T cells in the development of AD
      skin lesions in a mouse model of allergen-induced AD. In sensitized mice, CD8+ T
      cells are rapidly and transiently recruited to the allergen-exposed site and
      initiate the inflammatory process leading to skin infiltration with eosinophils
      and Th1/Th2-producing cells. CD8+ T cell-depleted mice show no inflammation,
      demonstrating that these cells are mandatory for the development of AD. In
      contrast, CD4+ T cell-depleted mice develop a severe form of eczema. Furthermore,
      adoptive transfer of CD8+ T cells from sensitized mice into naive recipient mice
      leads to skin inflammation soon after allergen exposure. These data indicate that
      allergen-primed CD8+ T cells are required for the development of AD-like lesions
      in mice.

PMID- 17442940
TI  - Autoimmune uveitis elicited with antigen-pulsed dendritic cells has a distinct
      clinical signature and is driven by unique effector mechanisms: initial encounter
      with autoantigen defines disease phenotype.
AB  - Human autoimmune uveitis is a heterogeneous group of potentially blinding ocular
      diseases in which most patients who exhibit immunity recognize the same retinal
      Ag. It is represented by the model of experimental autoimmune uveitis (EAU)
      induced in mice by immunization with retinal Ag in CFA. Murine EAU is
      characterized by a Th1/Th17 response pattern, which may not represent all types
      of human uveitis. We report in this study a new model of EAU induced by injection
      of matured dendritic cells loaded with a uveitogenic retinal peptide. Dendritic
      cell-induced EAU demonstrated unique characteristics compared with traditional
      EAU in terms of clinical manifestations, the nature of the inflammatory
      infiltrating cells, the cytokine response profile, and a strict requirement for
      IFN-gamma, whereas IL-17 appeared to play a minor role. Disease was self
      limiting, but could be reinduced with the same Ag in CFA, albeit with reduced
      severity, suggesting post-recovery resistance. Our study demonstrates in a
      disease setting that the context in which the same autoantigen is initially
      presented to the immune system precipitates distinct forms of pathology via a
      distinct pathogenic pathway on the same genetic background. These findings may
      shed new light on the complex biology and the heterogeneous nature of human
      uveitis, and provide an alternative model for uveitic diseases of immune origin.

PMID- 17442941
TI  - Protein inhibitor of activated STAT 3 modulates osteoclastogenesis by down
      regulation of NFATc1 and osteoclast-associated receptor.
AB  - Protein inhibitor of activated STAT3 (PIAS3) has been shown to regulate the
      activity of various transcription factors. In this study, we show that the
      overexpression of PIAS3 in bone marrow-derived monocyte/macrophage lineage cells
      attenuates osteoclast formation and down-regulates the expression of NFATc1 and
      osteoclast-associated receptor (OSCAR), which are important modulators in
      osteoclastogenesis. PIAS3 has been shown to associate with histone deacetylase 1
      as well as with transcription factors, including the microphthalmia transcription
      factor, NFATc1, and c-Fos. Moreover, overexpression of PIAS3 inhibits the
      transactivation of target genes such as NFATc1 and OSCAR. This inhibitory effect
      of PIAS3 is possibly mediated by histone deacetylase 1 recruitment to the
      promoter regions of NFATc1 and OSCAR. Furthermore, silencing of PIAS3 by RNA
      interference in osteoclast precursors enhances osteoclast formation as well as
      gene expression of NFATc1 and OSCAR. Taken together, our results reveal that
      PIAS3 acts as a modulator in osteoclastogenesis.

PMID- 17442942
TI  - CD200 expression on tumor cells suppresses antitumor immunity: new approaches to
      cancer immunotherapy.
AB  - Although the immune system is capable of mounting a response against many
      cancers, that response is insufficient for tumor eradication in most patients due
      to factors in the tumor microenvironment that defeat tumor immunity. We
      previously identified the immune-suppressive molecule CD200 as up-regulated on
      primary B cell chronic lymphocytic leukemia (B-CLL) cells and demonstrated
      negative immune regulation by B-CLL and other tumor cells overexpressing CD200 in
      vitro. In this study we developed a novel animal model that incorporates human
      immune cells and human tumor cells to address the effects of CD200 overexpression
      on tumor cells in vivo and to assess the effect of targeting Abs in the presence
      of human immune cells. Although human mononuclear cells prevented tumor growth
      when tumor cells did not express CD200, tumor-expressed CD200 inhibited the
      ability of lymphocytes to eradicate tumor cells. Anti-CD200 Ab administration to
      mice bearing CD200-expressing tumors resulted in nearly complete tumor growth
      inhibition even in the context of established receptor-ligand interactions.
      Evaluation of an anti-CD200 Ab with abrogated effector function provided evidence
      that blocking of the receptor-ligand interaction was sufficient for control of
      CD200-mediated immune modulation and tumor growth inhibition in this model. Our
      data indicate that CD200 expression by tumor cells suppresses antitumor responses
      and suggest that anti-CD200 treatment might be therapeutically beneficial for
      treating CD200-expressing cancers.

PMID- 17442943
TI  - Inhibitory receptor signals suppress ligation-induced recruitment of NKG2D to GM1
      rich membrane domains at the human NK cell immune synapse.
AB  - NKG2D is an activating receptor expressed on all human NK cells and a subset of T
      cells. In cytolytic conjugates between NK cells and target cells expressing its
      ligand MHC class I chain-related gene A, NKG2D accumulates at the immunological
      synapse with GM1-rich microdomains. Furthermore, NKG2D is specifically recruited
      to detergent-resistant membrane fractions upon ligation. However, in the presence
      of a strong inhibitory stimulus, NKG2D-mediated cytotoxicity can be intercepted,
      and recruitment of NKG2D to the immunological synapse and detergent-resistant
      membrane fractions is blocked. Also, downstream phosphorylation of Vav-1
      triggered by NKG2D ligation is circumvented by coengaging inhibitory receptors.
      Thus, we propose that one way in which inhibitory signaling can control NKG2D
      mediated activation is by blocking its recruitment to GM1-rich membrane domains.
      The accumulation of activating NK cell receptors in GM1-rich microdomains may
      provide the necessary platform from which stimulatory signals can proceed.

PMID- 17442944
TI  - Divergent effects of BAFF on human memory B cell differentiation into Ig
      secreting cells.
AB  - B cell-activating factor belonging to the TNF family (BAFF) plays a critical role
      in B cell maturation, yet its precise role in B cell differentiation into Ig
      secreting cells (ISCs) remains unclear. In this study, we find that upon
      isolation human naive and memory B (MB) cells have prebound BAFF on their
      surface, whereas germinal center (GC) B cells lack detectable levels of prebound
      BAFF. We attribute their lack of prebound BAFF to cell activation, because we
      demonstrate that stimulation of naive and MB cells results in the loss of
      prebound BAFF. Furthermore, the absence of prebound BAFF on GC B cells is not
      related to a lack of BAFF-binding receptors or an inability to bind exogenous
      BAFF. Instead, our data suggest that accessibility to soluble BAFF is limited
      within GCs, perhaps to prevent skewing of the conventional B cell differentiation
      program. In support of this concept, whereas BAFF significantly enhances ISC
      differentiation in response to T cell-dependent activation, we report for the
      first time the ability of BAFF to considerably attenuate ISC differentiation of
      MB cells in response to CpG stimulation, a form of T cell-independent activation.
      Our data suggest that BAFF may be providing regulatory signals during specific T
      cell-independent events, which protect the balance between MB cells and ISCs
      outside GCs. Taken together, these data define a complex role for BAFF in humoral
      immune responses and show for the first time that BAFF can also play an
      inhibitory role in B cell differentiation.

PMID- 17442945
TI  - Quantitatively reduced participation of anti-nuclear antigen B cells that down
      regulate B cell receptor during primary development in the germinal center/memory
      B cell response to foreign antigen.
AB  - The peripheral B cell compartment contains high levels of "polyreactivity"
      including autospecificities. We have described a pathway that certain
      autoreactive B cells may take in gaining stable access to the foreign Ag
      responsive peripheral compartment. This pathway was revealed in mice expressing a
      targeted Ig H chain transgene encoding BCRs with "multireactivity" for the hapten
      arsonate and DNA-based autoantigens. B cells expressing such BCRs develop to
      mature follicular phenotype and locale, and are not short-lived. These B cells
      express very low levels of BCR, indicating that they are not "ignorant" of self
      Ag, but do not display features of anergy in in vitro assays. Nonetheless, a
      variety of states of lymphocyte anergy has been described, and some may only be
      manifested in vivo. As such, we analyzed the ability of these B cells to
      participate in a T cell-dependent immune response to arsonate in vivo. These B
      cells mount an early primary response similar to control B cells, including
      homing to follicles, migration to the T-B interface, and induction of
      costimulatory molecules, proliferation, differentiation to AFCs, class switching,
      and entry into GCs and somatic hypermutation. Nonetheless, these B cells display
      reduced participation in the latter stages of the GC response and in the
      anamnestic AFC response. In total, these data suggest that while the
      autoreactivity of this type of B cell does not result in anergy, the ability of
      such B cells to participate in a cross-reactive immune response to foreign Ag is
      compromised.

PMID- 17442946
TI  - Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in
      clearance of apoptotic cells.
AB  - The clearance of apoptotic cells is important for regulating tissue homeostasis,
      inflammation, and autoimmune responses. The absence of receptor tyrosine kinases
      (Axl, Mertk, and Tyro3) results in widespread accumulation of apoptotic cells and
      autoantibody production in mice. In this report, we examine the function of the
      three family members in apoptotic cell clearance by different phagocytic cell
      types. Mertk elimination nearly abolished macrophage apoptotic cell phagocytosis;
      elimination of Axl, Tyro3, or both, reduced macrophage phagocytosis by
      approximately half, indicating that these also play a role. In contrast,
      apoptotic cell clearance in splenic and bone marrow-derived dendritic cells (DCs)
      is prolonged compared with macrophages and relied primarily on Axl and Tyro3. The
      slower ingestion may be due to lower DC expression of Axl and Tyro3 or absence of
      GAS6 expression, a known ligand for this receptor family. In vivo, phagocytosis
      of apoptotic material by retinal epithelial cells required Mertk. Unlike
      macrophages, there did not appear to be any role for Axl or Tyro3 in retinal
      homeostasis. Likewise, clearance of apoptotic thymocytes in vivo was dramatically
      reduced in mertk(kd) mice, but was normal in axl/tyro3(-/-) mice. Thus, cell and
      organ type specificity is clearly delineated, with DCs relying on Axl and Tyro3,
      retina and thymus requiring Mertk, and macrophages exhibiting an interaction that
      involves all three family members. Surprisingly, in macrophages, tyrosine
      phosphorylation of Mertk in response to apoptotic cells is markedly diminished
      from axl/tyro3(-/-) mice, suggesting that the interactions of these receptors by
      heterodimerization may be important in some cells.

PMID- 17442947
TI  - Tertiary lymphoid structures in the pancreas promote selection of B lymphocytes
      in autoimmune diabetes.
AB  - Autoimmune diabetes occurs when invading lymphocytes destroy insulin-producing
      beta cells in pancreatic islets. The role of lymphocytic aggregates at this
      inflammatory site is not understood. We find that B and T lymphocytes attacking
      islets in NOD mice organize into lymphoid structures with germinal centers.
      Analysis of BCR L chain genes was used to investigate selection of B lymphocytes
      in these tertiary lymphoid structures and in draining pancreatic lymph nodes. The
      pancreatic repertoire as a whole was found to be highly diverse, with the profile
      of L chain genes isolated from whole pancreas differing from that observed in
      regional lymph nodes. A Vkappa14 L chain predominated within the complex
      pancreatic repertoire of NOD mice. Skewing toward Vkappa4 genes was observed in
      the pancreas when the repertoire of NOD mice was restricted using a fixed Ig H
      chain transgene. Nucleotide sequencing of expressed Vkappas identified shared
      mutations in some sequences consistent with Ag-driven selection and clonal
      expansion at the site of inflammation. Isolated islets contained oligoclonal B
      lymphocytes enriched for the germinal center marker GL7 and for sequences
      containing multiple mutations within CDRs, suggesting local T-B interactions.
      Together, these findings identify a process that selects B lymphocyte
      specificities within the pancreas, with further evolution of the selected
      repertoire at the inflamed site. This interpretation is reinforced by Ag-binding
      studies showing a large population of insulin-binding B lymphocytes in the
      pancreas compared with draining lymph nodes.

PMID- 17442949
TI  - Lymphotoxin-independent expression of TNF-related activation-induced cytokine by
      stromal cells in cryptopatches, isolated lymphoid follicles, and Peyer's patches.
AB  - Stromal cells play a crucial role in the organogenesis of lymphoid tissues. We
      previously identified VCAM-1(+) stromal cells in cryptopatches (CP) and isolated
      lymphoid follicles (ILF) in the small intestine of C57BL/6 mice. Nonhemopoietic
      stromal cell networks in CP and ILF of adult mice also expressed FDC-M1, CD157
      (BP-3), and TNF-related activation-induced cytokine (TRANCE). Individual stromal
      cells were heterogeneous in their expression of these markers, with not all
      stromal cells expressing the entire set of stromal cell markers. Expression of
      VCAM-1, FDC-M1, and CD157 on CP stromal cells was absent in alymphoplasia mice
      deficient in NF-kappaB-inducing kinase (NIK) and NIK knockout mice.
      Administration of lymphotoxin beta receptor (LTbetaR)-Ig to wild-type mice on day
      13 resulted in the absence of CP on day 20; delaying administration of LTbetaR-Ig
      until day 18 resulted in an 80% decrease in the number of CP on day 22 and
      diminished expression of VCAM-1, FDC-M1, and CD157 on the remaining CP. In sharp
      contrast, TRANCE expression by stromal cells was completely independent of NIK
      and LTbetaR. In addition, expression of TRANCE in ILF was concentrated just
      beneath the follicle-associated epithelium, a pattern of polarization that was
      also observed in Peyer's patches. These findings suggest that TRANCE on stromal
      cells contributes to the differentiation and maintenance of organized lymphoid
      aggregates in the small intestine.

PMID- 17442948
TI  - Plasmid DNA vaccine-elicited cellular immune responses limit in vivo vaccine
      antigen expression through Fas-mediated apoptosis.
AB  - Particularly potent cellular or humoral immune responses are needed to confer
      protection in animal models against such pathogens as HIV/SIV, Mycobacterium
      tuberculosis, and malarial parasites. Persistent, high-level vaccine Ag
      expression may be required for eliciting such potent and durable immune
      responses. Although plasmid DNA immunogens are being explored as potential
      vaccines for protection against these pathogens, little is known about host
      factors that restrict long-term plasmid DNA vaccine Ag expression in vivo. We
      observed rapid damping of transgene expression from a plasmid DNA immunogen in
      wild-type, but not in T cell-deficient mice. This damping of Ag expression was
      temporally associated with the emergence of Ag-specific cellular immune
      responses. A requirement for Fas and the appearance of apoptotic nuclei at the
      site of vaccine inoculation suggest that T cells induce Fas-mediated apoptosis of
      plasmid DNA vaccine Ag-expressing cells. These studies demonstrate that high
      levels of in vivo Ag expression are associated with high-frequency cellular
      immune responses that in turn rapidly down-regulate vaccine Ag expression in
      vivo. These findings argue that it may not be possible to maintain persistent,
      high-level production of vaccine Ag in vivo to drive persistent immune responses
      as long as vaccine Ag production can be limited by host immune responses.

PMID- 17442950
TI  - Production of specific mRNA transcripts, usage of an alternate promoter, and
      octamer-binding transcription factors influence the surface expression levels of
      the HIV coreceptor CCR5 on primary T cells.
AB  - Surface levels of CCR5 on memory CD4(+) T cells influence HIV-1/AIDS
      susceptibility. Alternative promoter usage results in the generation of CCR5 mRNA
      isoforms that differ based on whether they contain or lack the untranslated exon
      1. The impact of exon 1-containing transcripts on CCR5 surface expression is
      unknown. In this study, we show that the increased cell surface expression of
      CCR5 on primary T cells is associated with selective enrichment of exon 1
      containing transcripts. The promoter that drives exon 1-containing transcripts is
      highly active in primary human T cells but not in transformed T cell lines. The
      transcription factors Oct-1 and -2 inhibit and enhance, respectively, the
      expression of exon 1-containing transcripts and CCR5 surface levels. However,
      polymorphisms at homologous octamer-binding sites in the CCR5 promoter of
      nonhuman primates abrogate the binding of these transcription factors. These
      results identify exon 1-containing transcripts, and the cis-trans factors that
      regulate the expression levels of these mRNA isoforms as key parameters that
      affect CCR5 surface expression levels, and by extension, susceptibility to
      HIV/AIDS among humans, and possibly, the observed interspecies differences in
      susceptibility to lentiviral infection.

PMID- 17442951
TI  - A teleost polymeric Ig receptor exhibiting two Ig-like domains transports
      tetrameric IgM into the skin.
AB  - The skin mucus IgM is an important molecule in the mucosal immune system of
      teleost skin. However, the transport mechanism associated with this molecule has
      yet to be clarified. In this study, we isolated a gene encoding a polymeric Ig
      receptor (pIgR) from a species of teleost fish, Takifugu rubripes (fugu). This
      gene is known to be an Ig transporter in the intestine of mammals. Our studies
      further demonstrated that fugu pIgR was expressed in the skin and that a fragment
      of pIgR bound to tetrameric IgM in the skin mucus. These results indicate that
      the skin pIgR transports tetrameric IgM into the skin mucus. The fugu pIgR
      exhibits a unique structure containing only two Ig-like domains corresponding to
      domain 1 and domain 4/5 of mammalian pIgR. This structure was sufficient for
      successful binding to tetrameric IgM. Teleost skin thus adopts the same Ig
      transport system as mammalian intestine via a unique pIgR.

PMID- 17442952
TI  - Regulation of alphabeta/gammadelta T cell development by the activator protein 1
      transcription factor c-Jun.
AB  - c-Jun is a member of the AP-1 family of transcription factors, the activity of
      which is strongly augmented by TCR signaling. To elucidate the functions of c-Jun
      in mouse thymic lymphopoiesis, we conditionally inactivated c-Jun specifically
      during early T cell development. The loss of c-Jun resulted in enhanced
      generation of gammadelta T cells, whereas alphabeta T cell development was
      partially arrested at the double-negative 3 stage. The increased generation of
      gammadelta T cells by loss of c-Jun was cell autonomous, because in a competitive
      reconstitution experiment the knockout-derived cells produced more gammadelta T
      cells than did the control cells. C-jun-deficient immature T cells failed to
      efficiently repress transcription of IL-7Ralpha, resulting in augmented IL
      7Ralpha mRNA and surface levels. Chromatin immunoprecipitation assays revealed
      binding of c-Jun to AP-1 binding sites present in the IL-7Ralpha promoter,
      indicating direct transcriptional regulation. Thus, c-Jun controls the
      transcription of IL-7Ralpha and is a novel regulator of the alphabeta/gammadelta
      T cell development.

PMID- 17442953
TI  - TNF trafficking to human mast cell granules: mature chain-dependent endocytosis.
AB  - Mast cells play a crucial role at the early stages of immune response against
      bacteria and parasites where their functionality is based on their capability of
      releasing highly bioactive compounds, among them TNF. Mast cells are considered
      the only cells storing preformed TNF, which allows for the immediate release of
      this cytokine upon contact with pathogens. We approached the question of
      mechanisms and amino acid motifs directing newly synthesized TNF for storage in
      cytoplasmic granules by analyzing the trafficking of a series of TNF-enhanced GFP
      fusion proteins in human mast cell lines HMC-1 and LAD2. Protein covering the
      full TNF sequence was successfully sorted into secretory granules in a process
      involving transient exposure on the outer membrane and re-endocytosis. In human
      cells, contrary to results previously obtained in a rodent model, TNF seems not
      to be glycosylated and, thus, trafficking is carbohydrate independent. In an
      effort to localize the amino acid motif responsible for granule targeting, we
      constructed additional fusion proteins and analyzed their trafficking, concluding
      that granule-targeting sequences are localized in the mature chain of TNF and
      that the cytoplasmic tail is expendable for endocytotic sorting of this cytokine,
      thus excluding direct interactions with intracellular adaptor proteins.

PMID- 17442954
TI  - Identification of the site of human mannan-binding lectin involved in the
      interaction with its partner serine proteases: the essential role of Lys55.
AB  - Mannan-binding lectin (MBL) is an oligomeric lectin that binds neutral
      carbohydrates on pathogens, forms complexes with MBL-associated serine proteases
      (MASP)-1, -2, and -3 and 19-kDa MBL-associated protein (MAp19), and triggers the
      complement lectin pathway through activation of MASP-2. To identify the MASP
      binding site(s) of human MBL, point mutants targeting residues C-terminal to the
      hinge region were produced and tested for their interaction with the MASPs and
      MAp19 using surface plasmon resonance and functional assays. Mutation Lys(55)Ala
      abolished interaction with the MASPs and MAp19 and prevented formation of
      functional MBL-MASP-2 complexes. Mutations Lys(55)Gln and Lys(55)Glu abolished
      binding to MASP-1 and -3 and strongly inhibited interaction with MAp19.
      Conversely, mutation Lys(55)Arg abolished interaction with MASP-2 and MAp19, but
      only weakened interaction with MASP-1 and -3. Mutation Arg(47)Glu inhibited
      interaction with MAp19 and decreased the ability of MBL to trigger the lectin
      pathway. Mutant Arg(47)Lys showed no interaction with the MASPs or MAp19, likely
      resulting from a defect in oligomerization. In contrast, mutation Arg(47)Ala had
      no impact on the interaction with the MASPs and MAp19, nor on the ability of MBL
      to trigger the lectin pathway. Mutation Pro(53)Ala only had a slight effect on
      the interaction with MASP-1 and -3, whereas mutations at residues Leu(49) and
      Leu(56) were ineffective. In conclusion, the MASP binding site of MBL involves a
      sequence stretch centered on residue Lys(55), which may form an ionic bond
      representing the major component of the MBL-MASP interaction. The binding sites
      for MASP-2/MAp19 and MASP-1/3 have common features but are not strictly
      identical.

PMID- 17442955
TI  - E2A and HEB are required to block thymocyte proliferation prior to pre-TCR
      expression.
AB  - Thymocytes undergoing TCRbeta gene rearrangements are maintained in a low or
      nonproliferating state during early T cell development. This block in cell cycle
      progression is not released until the expression of a functional pre-TCR, which
      is composed of a successfully rearranged TCRbeta-chain and the Pre-Talpha-chain.
      The regulatory molecules responsible for the coordination of these
      differentiation and proliferation events are currently unknown. E2A and HEB are
      structurally and functionally related basic helix-loop-helix transcription
      factors involved in T cell development. To reveal the function of E2A and HEB
      through the stage of pre-TCR expression and alleviate functional compensation
      between E2A and HEB, we use a double-conditional knockout model. The simultaneous
      deletion of E2A and HEB in developing thymocytes leads to a severe developmental
      block before pre-TCR expression and a dramatic reduction of Pre-Talpha
      expression. These developmentally arrested thymocytes exhibit increased
      proliferation in vivo and dramatic expansion ex vivo in response to IL-7
      signaling. These results suggest that E2A and HEB are not only critical for T
      cell differentiation but also necessary to retain developing thymocytes in cell
      cycle arrest before pre-TCR expression.

PMID- 17442956
TI  - Human TCR-binding affinity is governed by MHC class restriction.
AB  - T cell recognition is initiated by the binding of TCRs to peptide-MHCs (pMHCs),
      the interaction being characterized by weak affinity and fast kinetics.
      Previously, only 16 natural TCR/pMHC interactions have been measured by surface
      plasmon resonance (SPR). Of these, 5 are murine class I, 5 are murine class II,
      and 6 are human class I-restricted responses. Therefore, a significant gap exists
      in our understanding of human TCR/pMHC binding due to the limited SPR data
      currently available for human class I responses and the absence of SPR data for
      human class II-restricted responses. We have produced a panel of soluble TCR
      molecules originating from human T cells that respond to naturally occurring
      disease epitopes and their cognate pMHCs. In this study, we compare the binding
      affinity and kinetics of eight class-I-specific TCRs (TCR-Is) to pMHC-I with six
      class-II-specific TCRs (TCR-IIs) to pMHC-II using SPR. Overall, there is a
      substantial difference in the TCR-binding equilibrium constants for pMHC-I and
      pMHC-II, which arises from significantly faster on-rates for TCRs binding to pMHC
      I. In contrast, the off-rates for all human TCR/pMHC interactions fall within a
      narrow window regardless of class restriction, thereby providing experimental
      support for the notion that binding half-life is the principal kinetic feature
      controlling T cell activation.

PMID- 17442957
TI  - Protein kinase D interaction with TLR5 is required for inflammatory signaling in
      response to bacterial flagellin.
AB  - Protein kinase D (PKD), also called protein kinase C (PKC)mu, is a serine
      threonine kinase that is involved in diverse areas of cellular function such as
      lymphocyte signaling, oxidative stress, and protein secretion. After identifying
      a putative PKD phosphorylation site in the Toll/IL-1R domain of TLR5, we explored
      the role of this kinase in the interaction between human TLR5 and
      enteroaggregative Escherichia coli flagellin in human epithelial cell lines. We
      report several lines of evidence that implicate PKD in TLR5 signaling. First, PKD
      phosphorylated the TLR5-derived target peptide in vitro, and phosphorylation of
      the putative target serine 805 in HEK 293T cell-derived TLR5 was identified by
      mass spectrometry. Furthermore, mutation of serine 805 to alanine abrogated
      responses of transfected HEK 293T cells to flagellin. Second, TLR5 interacted
      with PKD in coimmunoprecipitation experiments, and this association was rapidly
      enhanced by flagellin treatment. Third, pharmacologic inhibition of PKC or PKD
      with Go6976 resulted in reduced expression and secretion of IL-8 and prevented
      the flagellin-induced activation of p38 MAPK, but treatment with the PKC
      inhibitor Go6983 had no significant effects on these phenotypes. Finally,
      involvement of PKD in the p38-mediated IL-8 response to flagellin was confirmed
      by small hairpin RNA-mediated gene silencing. Together, these results suggest
      that phosphorylation of TLR5 by PKD may be one of the proximal elements in the
      cellular response to flagellin, and that this event contributes to p38 MAPK
      activation and production of inflammatory cytokines in epithelial cells.

PMID- 17442958
TI  - Different evolutionary histories of the two classical class I genes BF1 and BF2
      illustrate drift and selection within the stable MHC haplotypes of chickens.
AB  - Compared with the MHC of typical mammals, the chicken MHC (BF/BL region) of the
      B12 haplotype is smaller, simpler, and rearranged, with two classical class I
      genes of which only one is highly expressed. In this study, we describe the
      development of long-distance PCR to amplify some or all of each class I gene
      separately, allowing us to make the following points. First, six other haplotypes
      have the same genomic organization as B12, with a poorly expressed (minor) BF1
      gene between DMB2 and TAP2 and a well-expressed (major) BF2 gene between TAP2 and
      C4. Second, the expression of the BF1 gene is crippled in three different ways in
      these haplotypes: enhancer A deletion (B12, B19), enhancer A divergence and
      transcription start site deletion (B2, B4, B21), and insertion/rearrangement
      leading to pseudogenes (B14, B15). Third, the three kinds of alterations in the
      BF1 gene correspond to dendrograms of the BF1 and poorly expressed class II B
      (BLB1) genes reflecting mostly neutral changes, while the dendrograms of the BF2
      and well-expressed class II (BLB2) genes each have completely different
      topologies reflecting selection. The common pattern for the poorly expressed
      genes reflects the fact the BF/BL region undergoes little recombination and
      allows us to propose a pattern of descent for these chicken MHC haplotypes from a
      common ancestor. Taken together, these data explain how stable MHC haplotypes
      predominantly express a single class I molecule, which in turn leads to striking
      associations of the chicken MHC with resistance to infectious pathogens and
      response to vaccines.

PMID- 17442959
TI  - Protection from direct cerebral cryptococcus infection by interferon-gamma
      dependent activation of microglial cells.
AB  - The brain represents a significant barrier for protective immune responses in
      both infectious disease and cancer. We have recently demonstrated that
      immunotherapy with anti-CD40 and IL-2 can protect mice against disseminated
      Cryptococcus infection. We now applied this immunotherapy using a direct cerebral
      cryptococcosis model to study direct effects in the brain. Administration of anti
      CD40 and IL-2 significantly prolonged the survival time of mice infected
      intracerebrally with Cryptococcus neoformans. The protection was correlated with
      activation of microglial cells indicated by the up-regulation of MHC II
      expression on brain CD45(low)CD11b(+) cells. CD4(+) T cells were not required for
      either the microglial cell activation or anticryptococcal efficacy induced by
      this immunotherapy. Experiments with IFN-gamma knockout mice and IFN-gammaR
      knockout mice demonstrated that IFN-gamma was critical for both microglial cell
      activation and the anticryptococcal efficacy induced by anti-CD40/IL-2.
      Interestingly, while peripheral IFN-gamma production and microglial cell
      activation were observed early after treatment, negligible IFN-gamma was detected
      locally in the brain. These studies indicate that immunotherapy using anti-CD40
      and IL-2 can augment host immunity directly in the brain against C. neoformans
      infection and that IFN-gamma is essential for this effect.

PMID- 17442960
TI  - T cell activation and proliferation characteristic for HIV-Nef transgenic mice is
      lymphopenia induced.
AB  - The HIV-Nef protein has been implicated in generating high viral loads and T cell
      activation. Transgenic (tg) mice with constitutive T cell-specific Nef expression
      show a dramatic reduction in T cell number and highly increased T cell turnover.
      Previous studies in Nef tg mice attributed this T cell activation to a direct
      effect of Nef at the cellular level. Given the strongly reduced peripheral T cell
      numbers, we examined whether this enhanced T cell division might instead be
      lymphopenia induced. Adoptively transferred naive wild-type T cells into
      lymphopenic Nef tg mice showed high T cell turnover and obtained the same
      effector/memory phenotype as the autologous Nef tg T cells, supporting the idea
      that the microenvironment determines the phenotype of the T cells present.
      Moreover, in bone marrow chimeras from mixtures of wild-type and Nef tg bone
      marrow, with a full T cell compartment containing a small proportion of Nef tg T
      cells, Nef tg T cells kept a naive phenotype. These results demonstrate that T
      cell activation in the Nef tg mice is lymphopenia induced rather than due to a
      direct T cell-activating effect of Nef.

PMID- 17442961
TI  - Coronin function is required for chemotaxis and phagocytosis in human
      neutrophils.
AB  - Coronins are a family of conserved actin-associated proteins that have been
      implicated in a variety of cellular processes dependent on actin rearrangements.
      In this study, we show that in primary human neutrophils, coronins-1-4 and -7 are
      expressed. Coronin-1 accumulates at the leading edge of migrating neutrophils and
      at the nascent phagosome. Inhibition of coronin function by transduction of a
      dominant-negative form of the protein leads to inhibition of chemotaxis and a
      reduction in neutrophil spreading and adhesion. This inhibition appears to
      correlate with changes in the distribution of F-actin structures within the cell.
      In addition, phagocytosis is inhibited, but neither secretion nor activation of
      the NADPH oxidase appears to be affected. Together, these results show that
      coronins are required for actin-dependent changes in cell morphology that lead to
      migration and phagocytosis.

PMID- 17442962
TI  - NK cells stimulate recruitment of CXCR3+ T cells to the brain during Plasmodium
      berghei-mediated cerebral malaria.
AB  - NK cells are cytotoxic lymphocytes that also secrete regulatory cytokines and can
      therefore influence adaptive immune responses. NK cell function is largely
      controlled by genes present in a genomic region named the NK complex. It has been
      shown that the NK complex is a genetic determinant of murine cerebral malaria
      pathogenesis mediated by Plasmodium berghei ANKA. In this study, we show that NK
      cells are required for cerebral malaria disease induction and the control of
      parasitemia. NK cells were found infiltrating brains of cerebral malaria-affected
      mice. NK cell depletion resulted in inhibition of T cell recruitment to the brain
      of P. berghei-infected animals. NK cell-depleted mice displayed down-regulation
      of CXCR3 expression and a significant reduction of T cells migrating in response
      to IFN-gamma-inducible protein 10, indicating that this chemokine pathway plays
      an essential role in leukocyte trafficking leading to cerebral disease and
      fatalities.

PMID- 17442963
TI  - Monocyte recruitment, activation, and function in the gut-associated lymphoid
      tissue during oral Salmonella infection.
AB  - Neutrophils, monocytes, and dendritic cells (DC) are phenotypically and
      functionally related phagocytes whose presence in infected tissues is critical to
      host survival. Their overlapping expression pattern of surface molecules, the
      differentiation capacity of monocytes, and the presence of monocyte subsets
      underscores the complexity of understanding the role of these cells during
      infection. In this study we use five- to seven-color flow cytometry to assess the
      phenotype and function of monocytes recruited to Peyer's patches (PP) and
      mesenteric lymph nodes (MLN) after oral Salmonella infection of mice. The data
      show that CD68(high)Gr-1(int) (intermediate) monocytes, along with CD68(int)Gr
      1(high) neutrophils, rapidly accumulate in PP and MLN. The monocytes have
      increased MHC-II and costimulatory molecule expression and, in contrast to
      neutrophils and DC, produce inducible NO synthase. Although neutrophils and
      monocytes from infected mice produce TNF-alpha and IL-1beta upon ex vivo culture,
      DC do not. In addition, although recruited monocytes internalize Salmonella in
      vitro and in vivo they did not induce the proliferation of OT-II CD4(+) T cells
      after coincubation with Salmonella expressing OVA despite their ability to
      activate OT-II cells when pulsed with the OVA(323-339) peptide. We also show that
      recruited monocytes enter the PP of infected mice independently of the mucosal
      address in cell adhesion molecule-1 (MAdCAM-1). Finally, recruited but not
      resident monocytes increase in the blood of orally infected mice, and MHC-II up
      regulation, but not TNF-alpha or iNOS production, occur already in the blood.
      These studies are the first to describe the accumulation and function of monocyte
      subsets in the blood and GALT during oral Salmonella infection.

PMID- 17442964
TI  - Antigen presentation by nonhemopoietic cells amplifies clonal expansion of
      effector CD8 T cells in a pathogen-specific manner.
AB  - Professional APCs of hemopoietic-origin prime pathogen-specific naive CD8 T
      cells. The primed CD8 T cells can encounter Ag on infected nonhemopoietic cell
      types. Whether these nonhemopoietic interactions perpetuate effector T cell
      expansion remains unknown. We addressed this question in vivo, using four viral
      and bacterial pathogens, by comparing expansion of effector CD8 T cells in bone
      marrow chimeric mice expressing restricting MHC on all cell types vs mice that
      specifically lack restricting MHC on nonhemopoietic cell types or radiation
      sensitive hemopoietic cell types. Absence of Ag presentation by nonhemopoietic
      cell types allowed priming of naive CD8 T cells in all four infection models
      tested, but diminished their sustained expansion by approximately 10-fold during
      lymphocytic choriomeningitis virus and by < or =2-fold during vaccinia virus,
      vesicular stomatitis virus, or Listeria monocytogenes infections. Absence of Ag
      presentation by a majority (>99%) of hemopoietic cells surprisingly also allowed
      initial priming of naive CD8 T cells in all the four infection models, albeit
      with delayed kinetics, but the sustained expansion of these primed CD8 T cells
      was markedly evident only during lymphocytic choriomeningitis virus, but not
      during vaccinia virus, vesicular stomatitis virus, or L. monocytogenes. Thus,
      infected nonhemopoietic cells can amplify effector CD8 T cell expansion during
      infection, but the extent to which they can amplify is determined by the
      pathogen. Further understanding of mechanisms by which pathogens differentially
      affect the ability of nonhemopoietic cell types to contribute to T cell
      expansion, how these processes alter during acute vs chronic phase of infections,
      and how these processes influence the quality and quantity of memory cells will
      have implications for rational vaccine design.

PMID- 17442965
TI  - Enrichment and persistence of virus-specific CTL in the brain of simian
      immunodeficiency virus-infected monkeys is associated with a unique cytokine
      environment.
AB  - The host reaction to infection of the brain contributes to a number of CNS
      pathologies including neuro-AIDS. In this study, we have identified the
      accumulation of SIV-specific CTL in the brains of SIV-infected animals who have
      neurophysiological abnormalities but are otherwise asymptomatic. SIV-specific CTL
      enter the brain early after viral infection and are maintained in the brain even
      when those reactive with an immunodominant epitope in Tat are lost from the rest
      of the body. The specialized CNS environment contributes to this unique outcome.
      Following SIV infection, brain levels of IL-15 were significantly elevated
      whereas IL-2 was absent, creating an environment that favors CTL persistence.
      Furthermore, in response to IL-15, brain-derived CD8(+) T cells could expand in
      greater numbers than those from spleen. The accumulation, persistence, and
      maintenance of CTL in the brain are closely linked to the increased levels of IL
      15 in the absence of IL-2 in the CNS following SIV infection.

PMID- 17442966
TI  - MyD88-mediated instructive signals in dendritic cells regulate pulmonary immune
      responses during respiratory virus infection.
AB  - Respiratory syncytial virus (RSV) is the leading cause of respiratory disease in
      infants worldwide. The induction of innate immunity and the establishment of
      adaptive immune responses are influenced by the recognition of pathogen
      associated molecular patterns by TLRs. One of the primary pathways for TLR
      activation is by MyD88 adapter protein signaling. The present studies indicate
      that MyD88 deficiency profoundly impacts the pulmonary environment in RSV
      infected mice characterized by the accumulation of eosinophils and augmented
      mucus production. Although there was little difference in CD4 T cell
      accumulation, there was also a significant decrease in conventional dendritic
      cells recruitment to the lungs of MyD88(-/-) mice. The exacerbation of RSV
      pathophysiology in MyD88(-/-) mice was associated with an enhanced Th2 cytokine
      profile that contributed to an inappropriate immune response. Furthermore, bone
      marrow-derived dendritic cells (BMDC) isolated from MyD88(-/-) mice were
      incapable of producing two important Th1 instructive signals, IL-12 and delta
      like4, upon RSV infection. Although MyD88(-/-) BMDCs infected with RSV did up
      regulate costimulatory molecules, they did not up-regulate class II as
      efficiently and stimulated less IFN-gamma from CD4(+) T cells in vitro compared
      with wild-type BMDCs. Finally, adoptive transfer of C57BL/6 BMDCs into MyD88(-/-)
      mice reconstituted Th1 immune responses in vivo, whereas transfer of MyD88(-/-)
      BMDCs into wild-type mice skewed the RSV responses toward a Th2 phenotype. Taken
      together, our data indicate that MyD88-mediated pathways are essential for the
      least pathogenic responses to this viral pathogen through the regulation of
      important Th1-associated instructive signals.

PMID- 17442967
TI  - Lung-specific overexpression of CC chemokine ligand (CCL) 2 enhances the host
      defense to Streptococcus pneumoniae infection in mice: role of the CCL2-CCR2
      axis.
AB  - Mononuclear phagocytes are critical components of the innate host defense of the
      lung to inhaled bacterial pathogens. The monocyte chemotactic protein CCL2 plays
      a pivotal role in inflammatory mononuclear phagocyte recruitment. In this study,
      we tested the hypothesis that increased CCL2-dependent mononuclear phagocyte
      recruitment would improve lung innate host defense to infection with
      Streptococcus pneumoniae. CCL2 transgenic mice that overexpress human CCL2
      protein in type II alveolar epithelial cells and secrete it into the alveolar air
      space showed a similar proinflammatory mediator response and neutrophilic
      alveolitis to challenge with S. pneumoniae as wild-type mice. However, CCL2
      overexpressing mice showed an improved pneumococcal clearance and survival
      compared with wild-type mice that was associated with substantially increased
      lung mononuclear phagocyte subset accumulations upon pneumococcal challenge.
      Surprisingly, CCL2 overexpressing mice developed bronchiolitis obliterans upon
      pneumococcal challenge. Application of anti-CCR2 Ab MC21 to block the CCL2-CCR2
      axis in CCL2 overexpressing mice, though completely abrogating bronchiolitis
      obliterans, led to progressive pneumococcal pneumonia. Collectively, these
      findings demonstrate the importance of the CCL2-CCR2 axis in the regulation of
      both the resolution/repair and remodelling processes after bacterial challenge
      and suggest that overwhelming innate immune responses may trigger bronchiolitis
      obliterans formation in bacterial lung infections.

PMID- 17442968
TI  - Vesicular stomatitis virus glycoprotein displaying retrovirus-like particles
      induce a type I IFN receptor-dependent switch to neutralizing IgG antibodies.
AB  - Vesicular stomatitis virus (VSV) infection rapidly induces IFN-alphabeta that
      confers initial survival, whereas long-term protection is mediated by
      neutralizing IgG responses. Because coadministration of IFN-alphabeta can enhance
      Ab responses against soluble Ags, we addressed whether virus-induced IFN
      alphabeta also had an impact on the induction of neutralizing Ab responses. To
      this end, we generated apathogenic retrovirus-like particles (VLP) displaying the
      VSV gp (VLP-VSV). Reminiscent of live VSV, VLP-VSV induced VSV-neutralizing IgM
      responses that switched to IgG in a T help-dependent manner. In type I IFN
      receptor-deficient (IFNAR(-/-)) mice, VLP-VSV injection elicited neutralizing
      IgM, whereas the IgG switch was absent. The lack of subclass switch was
      associated with a reduced germinal center reaction. Conditional knockout mice
      with a lymphocyte-specific IFNAR ablation showed normal Ab responses against VLP
      VSV, as well as against live VSV. Thus, IFNAR triggering critically promoted the
      T help-dependent subclass switch of virus-neutralizing Ab responses against VLP
      VSV. Interestingly, in the context of VLP-VSV as well as VSV immunization, IFNAR
      triggering of B lymphocytes did not play a critical role.

PMID- 17442969
TI  - The host immune regulator factor H interacts via two contact sites with the PspC
      protein of Streptococcus pneumoniae and mediates adhesion to host epithelial
      cells.
AB  - Pneumococcal surface protein C (PspC) of Streptococcus pneumoniae is a key
      virulence factor that mediates adhesion to host cells and immune evasion of the
      host complement. PspC binds the host immune and complement regulator factor H,
      which is composed of 20 short consensus repeats (SCR). This interaction
      contributes to pneumococcal virulence. In this study, we identified within the
      factor H protein two separate PspC binding regions, which were localized to SCR8
      11 and SCR19-20, by using recombinant factor H deletion constructs for Western
      blotting assays and surface plasmon resonance studies. A detailed analysis of
      binding epitopes in these SCR by peptide spot arrays identified several linear
      binding regions within the sequences of SCR8-11 and SCR19-20. In addition, the
      factor H binding site was mapped within the pneumococcal PspC protein to a 121-aa
      long stretch positioned in the N terminus (residues 38-158). Factor H attached to
      the surface of pneumococci via PspC significantly enhanced pneumococcal adherence
      to host epithelial and endothelial cells. This adhesion was specific and was
      blocked with a truncated N-terminal factor H-binding fragment of PspC. In
      conclusion, the acquisition of factor H by pneumococci via PspC occurs via two
      contact sites located in SCR8-11 and SCR19-20, and factor H attached to the
      surface of the pneumococcus promotes adhesion to both host epithelial and
      endothelial cells.

PMID- 17442970
TI  - Induction of IL-13 triggers TGF-beta1-dependent tissue fibrosis in chronic 2,4,6
      trinitrobenzene sulfonic acid colitis.
AB  - To investigate the immunopathogenesis of inflammation-associated fibrosis, we
      analyzed the chronic colitis and late-developing fibrosis occurring in BALB/c
      mice administered weekly doses of intrarectal 2,4,6-trinitrobenzene sulfonic
      acid. We showed first in this model that an initial Th1 response involving IL
      12p70 and IFN-gamma subsides after 3 wk to be supplanted by an IL-23/IL-25
      response beginning after 4-5 wk. This evolution is followed by gradually
      increasing production of IL-17 and cytokines ordinarily seen in a Th2 response,
      particularly IL-13, which reaches a plateau at 8-9 wk. In vitro stimulation
      studies suggest that this IL-13 production is dependent on IL-23 and IL-25, but
      not on IL-12p70. We then show that IL-13 production results in the induction of
      an IL-13R formerly thought to function only as a decoy receptor, IL-13Ralpha(2),
      and this receptor is critical to the production of TGF-beta(1) and the onset of
      fibrosis. Thus, if IL-13 signaling through this receptor is blocked by
      administration of soluble IL-13Ralpha(2)-Fc, or by administration of IL
      13Ralpha(2)-specific small interfering RNA, TGF-beta(1) is not produced and
      fibrosis does not occur. These studies show that in chronic 2,4,6-trinitrobenzene
      sulfonic acid colitis, fibrosis is dependent on the development of an IL-13
      response that acts through a novel cell surface-expressed IL-13R to induce TGF
      beta(1). A similar mechanism may obtain in certain forms of human inflammatory
      bowel disease.

PMID- 17442971
TI  - Neutrophil elastase up-regulates cathepsin B and matrix metalloprotease-2
      expression.
AB  - Neutrophil elastase (NE) activity is increased in many diseases. Other families
      of proteases, including cathepsins and matrix metalloproteases (MMPs), are also
      present at elevated levels in similar disease conditions. We postulated that NE
      could induce expression of cathepsins and MMPs in human macrophages. NE exposure
      resulted in macrophages, producing significantly greater amounts of cathepsin B
      and latent and active MMP-2. Cathepsin B and MMP-2 activities were decreased in
      Pseudomonas-infected NE knockout mice compared with wild-type littermates. We
      also demonstrate that NE can activate NF-kappaB in macrophages, and inhibition of
      NF-kappaB resulted in a reduction of NE-induced cathepsin B and MMP-2. Also,
      inhibition of TLR-4 or transfection of macrophages with dominant-negative IL-1R
      associated kinase-1 resulted in a reduction of NE-induced cathepsin B and MMP-2.
      This study describes for the first time a novel hierarchy among proteases whereby
      a serine protease up-regulates expression of MMPs and cathepsins. This has
      important implications for therapeutic intervention in protease-mediated
      diseases.

PMID- 17442972
TI  - Neutrophil transmigration under shear flow conditions in vitro is junctional
      adhesion molecule-C independent.
AB  - Endothelial cell junctional adhesion molecule (JAM)-C has been proposed to
      regulate neutrophil migration. In the current study, we used function-blocking
      mAbs against human JAM-C to determine its role in human leukocyte adhesion and
      transendothelial cell migration under flow conditions. JAM-C surface expression
      in HUVEC was uniformly low, and treatment with inflammatory cytokines TNF-alpha,
      IL-1beta, or LPS did not increase its surface expression as assessed by FACS
      analysis. By immunofluorescence microscopy, JAM-C staining showed sparse
      localization to cell-cell junctions on resting or cytokine-activated HUVEC.
      Surprisingly, staining of detergent-permeabilized HUVEC revealed a large
      intracellular pool of JAM-C that showed little colocalization with von Willebrand
      factor. Adhesion studies in an in vitro flow model showed that functional
      blocking JAM-C mAb alone had no inhibitory effect on polymorphonuclear leukocyte
      (PMN) adhesion or transmigration, whereas mAb to ICAM-1 significantly reduced
      transmigration. Interestingly, JAM-C-blocking mAbs synergized with a combination
      of PECAM-1, ICAM-1, and CD99-blocking mAbs to inhibit PMN transmigration.
      Overexpression of JAM-C by infection with a lentivirus JAM-C GFP fusion protein
      did not increase adhesion or extent of transmigration of PMN or evoke a role for
      JAM-C in transendothelial migration. These data suggest that JAM-C has a minimal
      role, if any, in PMN transmigration in this model and that ICAM-1 is the
      preferred endothelial-expressed ligand for PMN beta(2) integrins during
      transendothelial migration.

PMID- 17442973
TI  - Dual effect of AMD3100, a CXCR4 antagonist, on bleomycin-induced lung
      inflammation.
AB  - The chemokine receptor CXCR4, which binds the chemokine stromal cell-derived
      factor 1, has been reported to be involved in the chemotaxis of inflammatory
      cells. In addition, AMD3100, an antagonist of CXCR4, has been reported to be an
      attractive drug candidate for therapeutic intervention in several disorders in
      which CXCR4 is critically involved. However, little is known about the
      therapeutic value of AMD3100 in the treatment of pulmonary fibrosis. In this
      study, we examined the effects of AMD3100 on a murine bleomycin-induced pulmonary
      fibrosis model. Concurrent administration of AMD3100 and bleomycin apparently
      attenuated bleomycin-induced pulmonary inflammation. In this process, an
      inhibition of neutrophil recruitment at early stage followed by the decrease of
      other inflammatory cell recruitment in the lung were observed. In addition, it
      also inhibited the expression of cytokines, including MCP-1, MIP-2, MIP-1alpha,
      and TGF-beta. In contrast, when AMD3100 was administered following bleomycin
      treatment, the bleomycin-induced lung inflammation progressed and resulted in
      severe pulmonary fibrosis. In this process, an increase of inflammatory cell
      recruitment, an up-regulation of lung MCP-1 and TGF-beta, and a remarkable
      activation of p44/42 MAPK in neutrophils were observed. U0126, an inhibitor of
      p44/42 MAPK, significantly abolished these effects. Thus, AMD3100 has dual effect
      on bleomycin-induced pulmonary fibrosis. Difference of inflammatory cell
      recruitment and activation might be associated with the dual effect of AMD3100 on
      bleomycin-induced pulmonary fibrosis.

PMID- 17442974
TI  - NKT cell activation mediates neutrophil IFN-gamma production and renal ischemia
      reperfusion injury.
AB  - Previous work has shown that ischemia-reperfusion (IR) injury (IRI) is dependent
      on CD4(+) T cells from naive mice acting within 24 h. We hypothesize that NKT
      cells are key participants in the early innate response in IRI. Kidneys from
      C57BL/6 mice were subjected to IRI (0.5, 1, 3, and 24 h of reperfusion). After 30
      min of reperfusion, we observed a significant increase in CD4(+) cells (145% of
      control) from single-cell kidney suspensions as measured by flow cytometry. A
      significant fraction of CD4(+) T cells expressed the activation marker, CD69(+),
      and adhesion molecule, LFA-1(high). Three hours after reperfusion, kidney IFN
      gamma-producing cells were comprised largely of GR-1(+)CD11b(+) neutrophils, but
      also contained CD1d-restricted NKT cells. Kidney IRI in mice administered Abs to
      block CD1d, or deplete NKT cells or in mice deficient of NKT cells (Jalpha18(-/
      )), was markedly attenuated. These effects were associated with a significant
      decrease in renal infiltration and, in activation of NKT cells, and a decrease in
      IFN-gamma-producing neutrophils. The results support the essential role of NKT
      cells and neutrophils in the innate immune response of renal IRI by mediating
      neutrophil infiltration and production of IFN-gamma.

PMID- 17442975
TI  - Scavenger Receptors SR-AI/II and MARCO limit pulmonary dendritic cell migration
      and allergic airway inflammation.
AB  - The class A scavenger receptors (SR-A) MARCO and SR-AI/II are expressed on lung
      macrophages (MPhis) and dendritic cells (DCs) and function in innate defenses
      against inhaled pathogens and particles. Increased expression of SR-As in the
      lungs of mice in an OVA-asthma model suggested an additional role in modulating
      responses to an inhaled allergen. After OVA sensitization and aerosol challenge,
      SR-AI/II and MARCO-deficient mice exhibited greater eosinophilic airway
      inflammation and airway hyperresponsiveness compared with wild-type mice. A role
      for simple SR-A-mediated Ag clearance ("scavenging") by lung MPhis was excluded
      by the observation of a comparable uptake of fluorescent OVA by wild-type and SR
      A-deficient lung MPhis and DCs. In contrast, airway instillation of fluorescent
      Ag revealed a significantly higher traffic of labeled DCs to thoracic lymph nodes
      in SR-A-deficient mice than in controls. The increased migration of SR-A
      deficient DCs was accompanied by the enhanced proliferation in thoracic lymph
      nodes of adoptively transferred OVA-specific T cells after airway OVA challenge.
      The data identify a novel role for SR-As expressed on lung DCs in the down
      regulation of specific immune responses to aeroallergens by the reduction of DC
      migration from the site of Ag uptake to the draining lymph nodes.

PMID- 17442976
TI  - Cross-regulation of carbon monoxide and the adenosine A2a receptor in
      macrophages.
AB  - Adenosine and heme oxygenase-1 (HO-1) exert a wide range of anti-inflammatory and
      immunomodulatory actions, making them crucial regulatory molecules. Despite the
      diversity in their modes of action, the similarity of biological effects of
      adenosine and HO-1 led us to hypothesize a possible interrelationship between
      them. We assessed a potential role for HO-1 in the ability of adenosine or 5'-N
      ethylcarboxamidoadenosine (NECA), a stable adenosine analog, to modify the
      response of LPS-stimulated macrophages. Adenosine and NECA markedly induced HO-1
      and blocked LPS-induced TNF-alpha production via adenosine A2aR-mediated
      signaling; blocking of HO-1 by RNA interference abrogated the effects of
      adenosine and NECA on TNF-alpha. HO-1 overexpression or exposure to carbon
      monoxide (CO), a product of HO-1 enzymatic activity, resulted in augmented A2aR
      mRNA and protein levels in RAW264.7 cells and primary macrophages. The induction
      of A2aR expression by HO-1 or CO resulted in an increase in the sensitivity to
      the anti-inflammatory effects of adenosine and NECA, which was lost in
      macrophages isolated from A2aR-deficient mice. Moreover, a decrease in cAMP
      levels upon NECA stimulation of naive macrophages was counterbalanced by CO
      exposure to up-regulate A2aR levels. This implies adenosine receptor isoform
      switch as a selective modification in macrophage phenotype. Taken together, these
      data suggest the existence of a positive feedback loop among adenosine, HO-1, CO,
      and the A2aR in the chronological resolution of the inflammatory response.

PMID- 17442977
TI  - Interactions between CD47 and thrombospondin reduce inflammation.
AB  - CD47 on the surface of T cells was shown in vitro to mediate either T cell
      activation or, in the presence of high amounts of thrombospondin (TSP), T cell
      apoptosis. We report here that CD47-deficient mice, as well as TSP-1 or TSP-2
      deficient mice, sustain oxazolone-induced inflammation for more than four days,
      whereas wild-type mice reduce the inflammation within 48 h. We observe that
      prolonged inflammation in CD47-, TSP-1-, or TSP-2-deficient mice is accompanied
      by a local deficiency of T cell apoptosis. Finally, we show that upon activation
      normal T cells increase the expression of the proapoptotic Bcl-2 family member
      BNIP3 (Bcl-2/adenovirus E1B 19-kDa interacting protein) and undergo CD47-mediated
      apoptosis. This finding is consistent with our previous demonstration of a
      physical interaction between BNIP3 and CD47 that inhibits BNIP3 degradation by
      the proteasome, sensitizing T cells to CD47-induced apoptosis. Overall, these
      results reveal an important role in vivo for this new CD47/BNIP3 pathway in
      limiting inflammation by controlling the number of activated T cells.

PMID- 17442978
TI  - The phosphatidylinositol 3-kinase signaling pathway exerts protective effects
      during sepsis by controlling C5a-mediated activation of innate immune functions.
AB  - The PI3K/Akt signaling pathway has been recently suggested to have controversial
      functions in models of acute and chronic inflammation. Our group and others have
      reported previously that the complement split product C5a alters neutrophil
      innate immunity and cell signaling during the onset of sepsis and is involved in
      PI3K activation. We report in this study that in vivo inhibition of the PI3K
      pathway resulted in increased mortality in septic mice accompanied by strongly
      elevated serum levels of TNF-alpha, IL-6, MCP-1, and IL-10 during sepsis as well
      as decreased oxidative burst activity in blood phagocytes. PI3K inhibition in
      vitro resulted in significant increases in TLR-4-mediated generation of various
      proinflammatory cytokines in neutrophils, whereas the opposite effect was
      observed in PBMC. Oxidative burst and phagocytosis activity was significantly
      attenuated in both neutrophils and monocytes when PI3K activation was blocked. In
      addition, PI3K inhibition resulted in strongly elevated TLR-4-mediated generation
      of IL-1beta and IL-8 in neutrophils when these cells were co-stimulated with C5a.
      C5a-induced priming effects on neutrophil and monocyte oxidative burst activity
      as well as C5a-induced phagocytosis in neutrophils were strongly reduced when
      PI3K activation was blocked. Our data suggest that the PI3K/Akt signaling pathway
      controls various C5a-mediated effects on neutrophil and monocyte innate immunity
      and exerts an overall protective effect during experimental sepsis.

PMID- 17442979
TI  - Systemic inflammatory priming in normal pregnancy and preeclampsia: the role of
      circulating syncytiotrophoblast microparticles.
AB  - Systemic inflammatory responsiveness was studied in normal human pregnancy and
      its specific inflammatory disorder, pre-eclampsia. Compared with nonpregnancy,
      monocytes were primed to produce more TNF-alpha throughout normal pregnancy, more
      IL-12p70 in the first and second trimesters, and more IL-18 in the first
      trimester only. Intracellular cytokine measurements (TNF-alpha and IL12p70)
      showed little change by comparison. IFN-gamma production was suppressed in all
      three trimesters. In pre-eclampsia, IL-18 secretion was increased. Secreted but
      not intracellular measures of TNF-alpha and IL-12p70 were also further enhanced
      compared with normal pregnancy. Inhibition of IFN-gamma production was lost and
      involved both CD56(+) NK and CD56(-) lymphocyte subsets. We determined whether
      circulating syncytiotrophoblast microparticles (STBM) could contribute to these
      inflammatory changes. Unbound STBM could be detected in normal pregnancy by the
      second trimester and increased significantly in the third. They were also bound
      in vivo to circulating monocytes. Women with pre-eclampsia had significantly more
      circulating free but not cell-bound STBMs. STBMs prepared by perfusion of normal
      placental lobules stimulated production of inflammatory cytokines (TNF-alpha,
      IL12p70, and IL-18 but not IFN-gamma) when cultured with PBMCs from healthy
      nonpregnant women. Inflammatory priming of PBMCs during pregnancy is confirmed
      and is established by the first trimester. It is associated with early inhibition
      of IFN-gamma production. The inflammatory response is enhanced in pre-eclampsia
      with loss of the IFN-gamma suppression. Circulating STBMs bind to monocytes and
      stimulate the production of inflammatory cytokines. It is concluded that they are
      potential contributors to altered systemic inflammatory responsiveness in
      pregnancy and pre-eclampsia.

PMID- 17442980
TI  - IL-21 is highly produced in Helicobacter pylori-infected gastric mucosa and
      promotes gelatinases synthesis.
AB  - Helicobacter pylori (Hp) infection is associated with gastric inflammation and
      ulceration. The pathways of tissue damage in Hp-infected subjects are complex,
      but evidence indicates that T cell-derived cytokines enhance the synthesis of
      matrix metalloproteinases (MMP) that contribute to mucosal ulceration and
      epithelial damage. In this study, we have examined the role of the T cell
      cytokine IL-21 in Hp-infected gastric mucosa and evaluated whether IL-21
      regulates MMP production by gastric epithelial cells. We show that IL-21 is
      constitutively expressed in gastric mucosa and is more abundant in biopsy
      specimens and purified mucosal CD3(+) T cells from Hp-infected patients compared
      with normal patients and disease controls. We also demonstrate that IL-21R is
      expressed by primary gastric epithelial cells, as well as by the gastric
      epithelial cell lines AGS and MKN28. Consistently, AGS cells respond to IL-21 by
      increasing production of MMP-2 and MMP-9, but not MMP-1, MMP-3, MMP-7, or tissue
      inhibitors of MMP. Analysis of signaling pathways leading to MMP production
      reveals that IL-21 enhances NF-kappaB but not MAPK activation, and inhibition of
      NF-kappaB activation reduces IL-21-induced MMP-2 and MMP-9 production. Finally,
      we show that treatment of Hp-infected gastric explants with anti-IL-21 reduces
      epithelial cell-derived MMP-2 and MMP-9 production. These data indicate that IL
      21 is overexpressed in Hp-infected gastric mucosa where it could contribute to
      increased epithelial gelatinase production.

PMID- 17442981
TI  - Genetic stability of human T lymphotropic virus type I despite antiviral
      pressures by CTLs.
AB  - Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic
      paraparesis (HAM/TSP) is an inflammatory neurological disease. Patients with
      HAM/TSP show high proviral load despite increased HTLV-I Tax-specific CTL. It is
      still unknown whether the CTL efficiently eliminate the virus in vivo and/or
      whether a naturally occurring variant virus becomes predominant by escaping from
      the CTL. To address these issues, we sequenced a large number of HTLV-I tax genes
      from HLA-A*02 HAM/TSP patients and estimated synonymous and nonsynonymous changes
      of the genes to detect positive selection pressure on the virus. We found the
      pressures in three of six CTL epitopes in HTLV-I Tax, where amino acid
      substitutions preferentially occurred. Although some of variant viruses were not
      recognized by the CTL, no variant viruses accumulated within 3-8 years,
      indicating genetic stability of HTLV-I tax gene. These results suggest that CTL
      eliminate the infected cells in vivo and naturally occurring variant viruses do
      not predominate. As Tax is a regulatory protein which controls viral replication,
      the amino acid substitutions in Tax may reduce viral fitness for replication.
      Viral fitness and host immune response may contribute to the viral evolution
      within the infected individuals. Furthermore, the genetic stability in the
      epitopes despite the antiviral pressures suggests that the three epitopes can be
      the candidate targets for HTLV-I vaccine development.

PMID- 17442982
TI  - IL-22 induces lipopolysaccharide-binding protein in hepatocytes: a potential
      systemic role of IL-22 in Crohn's disease.
AB  - Crohn's disease (CD) is a common, chronic, inflammatory bowel disease
      characterized by intestinal infiltration of activated immune cells and distortion
      of the intestinal architecture. In this study, we demonstrate that IL-22, a
      cytokine that is mainly produced by activated Th1 and Th17 cells, was present in
      high quantities in the blood of CD patients in contrast to IFN-gamma and IL-17.
      In a mouse colitis model, IL-22 mRNA expression was elevated predominantly in the
      inflamed intestine but also in the mesenteric lymph nodes. IL-22BP, the soluble
      receptor for IL-22, demonstrated an affinity to IL-22 that was at least 4-fold
      higher than its membrane-bound receptor, and its strong constitutive expression
      in the intestine and lymph nodes was decreased in the inflamed intestine. To
      investigate the possible role of systemic IL-22 in CD, we then administered IL-22
      to healthy mice and found an up-regulation of LPS-binding protein (LBP) blood
      levels reaching concentrations known to neutralize LPS. This systemic up
      regulation was associated with increased hepatic but not renal or pulmonary LBP
      mRNA levels. IL-22 also enhanced the secretion of LBP in human primary
      hepatocytes and HepG2 hepatoma cells in vitro. This increase was mainly
      transcriptionally regulated and synergistic with that of other LBP inducers.
      Finally, elevated LBP levels were detected in CD patients and the mouse colitis
      model. These data suggest that systemic IL-22 may contribute to the prevention of
      systemic inflammation provoked by LPS present in the blood of CD patients through
      its induction of hepatic LBP.

PMID- 17442983
TI  - Dissecting the anti-desmoglein autoreactive B cell repertoire in pemphigus
      vulgaris patients.
AB  - Pemphigus vulgaris (PV) encompasses two clinical phenotypes, one producing
      mucosal blisters and the other mucosal and skin lesions (mcPV). The mucosal
      blister-producing PV variant is characterized by autoantibodies against
      desmoglein (Dsg)3, whereas mucosal and skin lesion-producing PV is characterized
      by autoantibodies to Dsg3 and Dsg1. The present study was aimed at disclosing the
      diversity and clonality of the anti-Dsg3 response, as well as whether anti-Dsg3 B
      cells are Ag selected. Human-mouse heterohybridomas were generated by fusion of
      EBV-transformed or freshly isolated PBLs from six PV patients with mouse myeloma
      cells. A total of 73 anti-Dsg hybridomas (47 IgM and 26 IgG) were isolated. Over
      90% are specific for both Dsg1 and Dsg3 indicating extensive cross-reactivity
      between these responses. V(H) gene segment use by IgM hybridomas is diverse, but
      is restricted among IgG hybridomas, where the majority uses one of two V(H)
      genes. V(L) gene segment use was diverse even among IgG hybridomas suggesting
      that the V(L) is less critical to defining desmoglein specificity. Additionally,
      the IgG hybridomas were extensively mutated and the distribution and nature of
      the mutations suggested that they had been Ag selected. We conclude that the
      potentially pathogenic IgG anti-Dsg response is restricted in V(H) use, is
      somatically mutated, and is Ag selected.

PMID- 17442984
TI  - Down-regulation of human complement factor H sensitizes non-small cell lung
      cancer cells to complement attack and reduces in vivo tumor growth.
AB  - Malignant cells are often resistant to complement activation through the enhanced
      expression of complement inhibitors. In this work, we examined the protective
      role of factor H, CD46, CD55, and CD59 in two non-small cell lung cancer cell
      lines, H1264 and A549, upon activation of the classical pathway of complement.
      Complement was activated with polyclonal Abs raised against each cell line. After
      blocking factor H activity with a neutralizing Ab, C3 deposition and C5a release
      were more efficient. Besides, a combined inhibition of factor H and CD59
      significantly increased complement-mediated lysis. CD46 and CD55 did not show any
      effect in the control of complement activation. Factor H expression was knockdown
      on A549 cells using small interfering RNA. In vivo growth of factor H-deficient
      cells in athymic mice was significantly reduced. C3 immunocytochemistry on
      explanted xenografts showed an enhanced activation of complement in these cells.
      Besides, when mice were depleted of complement with cobra venom factor, growth
      was recovered, providing further evidence that complement was important in the
      reduction of in vivo growth. In conclusion, we show that expression of the
      complement inhibitor factor H by lung cancer cells can prevent complement
      activation and improve tumor development in vivo. This may have important
      consequences in the efficiency of complement-mediated immunotherapies.

PMID- 17442986
TI  - Methylguanine methyltransferase testing in glioblastoma: when and how?

PMID- 17442987
TI  - Cancer chemoprevention: how do we know what works?

PMID- 17442988
TI  - Confronting medical errors in oncology and disclosing them to cancer patients.

PMID- 17442989
TI  - Correlation between O6-methylguanine-DNA methyltransferase and survival in
      inoperable newly diagnosed glioblastoma patients treated with neoadjuvant
      temozolomide.
AB  - PURPOSE: This phase II study evaluated the efficacy and safety of a 7-day on/7
      day off regimen of temozolomide before radiotherapy (RT) in patients with
      inoperable newly diagnosed glioblastoma. PATIENTS AND METHODS: Patients received
      temozolomide (150 mg/m2/d on days 1 to 7 and days 15 to 21 every 28 days; 7 days
      on/7 days off) for up to four cycles before conventional RT (2-Gy fractions to a
      total of 60 Gy) and for four cycles thereafter or until disease progression. The
      primary end point was tumor response. Tumor tissue from 25 patients was analyzed
      for O6-methylguanine-DNA methyltransferase (MGMT) expression. RESULTS: Twenty
      nine patients with a median age of 60 years were treated, and 28 were assessable
      for response. Seven (24%) of 29 patients had a partial response, nine patients
      (31%) had stable disease, and 12 patients (41%) had progressive disease. Median
      progression-free survival (PFS) time was 3.8 months, and median overall survival
      (OS) time was 6.1 months. Patients with low MGMT expression, compared with
      patients with high MGMT expression, had a significantly higher response rate (55%
      v 7%, respectively; P = .004) and improved PFS (median, 5.5 v 1.9 months,
      respectively; P = .009) and OS (median, 16 v 5 months, respectively; P = .003).
      The most common grade 3 and 4 toxicities were thrombocytopenia (20%) and
      neutropenia (17%). CONCLUSION: This dose-dense temozolomide regimen resulted in
      modest antitumor activity with an acceptable safety profile in the neoadjuvant
      setting, and expression of MGMT correlated with response to temozolomide.
      However, this treatment approach seems to be inferior to standard concomitant RT
      plus temozolomide.

PMID- 17442990
TI  - Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients
      with diabetes.
AB  - PURPOSE: Peroxisome proliferator-activated receptor gamma (PPARgamma) mediates
      cell cycle arrest and adipocyte differentiation; has tumor suppressor activity in
      liposarcoma, lung, and prostate cancers; and suppresses colonic polyp formation
      in adenomatous polyposis coli (APC)min/+ mice. To assess the influence of
      thiazolidinediones (TZDs), which are PPAR ligands used to treat diabetes
      mellitus, a retrospective analysis of a database from 10 Veteran Affairs medical
      centers was conducted. PATIENTS AND METHODS: Data on male patients 40 years and
      older diagnosed to have diabetes mellitus between 1997 and 2003 were obtained
      from the Veterans Integrated Services Network 16 (VISN 16) data warehouse.
      Subsequent diagnoses of colorectal, lung, and prostate cancer and use of TZD,
      other antidiabetic agents, and insulin were identified. Cox regression with time
      dependent covariates was used to estimate the association between TZD use and
      cancer risk. Relative risks were adjusted for confounders (age, race/ethnicity,
      body mass index, use of insulin, and other oral antidiabetic agents). RESULTS: Of
      87,678 individuals, 1,137 had colorectal cancer, 3,246 had prostate cancer, and
      1,371 had lung cancer. We observed a 33% reduction in lung cancer risk among TZD
      users compared with nonusers after adjusting for confounder interactions
      (relative risk, 0.67; 95% CI, 0.51 to 0.87). The risk reduction for colorectal
      and prostate cancers did not reach statistical significance. CONCLUSION: TZD use
      was associated with reduced risk of lung cancer. Further studies are warranted to
      confirm our findings.

PMID- 17442991
TI  - High body mass index increases the risk for osteonecrosis in children with acute
      lymphoblastic leukemia.
AB  - PURPOSE: The aim of the study was to determine the incidence of and clinical risk
      factors for radiographic osteonecrosis (ON) in children treated for acute
      lymphoblastic leukemia (ALL) using the Nordic ALL protocols. PATIENTS AND
      METHODS: Ninety-seven consecutive patients with childhood ALL were studied
      prospectively by magnetic resonance imaging (MRI) of the lower extremities at the
      end of the treatment. RESULTS: Twenty-three (24%) of the 97 patients had ON.
      Seven of the patients (30%) were symptomatic, and three patients (13%) required
      surgical interventions. Multiple logistic regression analysis showed that high
      body mass index (BMI; P = .04), female sex (P = .01), older age at diagnosis (P <
      .001), and higher cumulative dexamethasone dose (P = .03) were independent risk
      factors for radiographic ON. The cumulative prednisone dose did not differ
      significantly between the patients with and without ON. The incidence of
      radiographic ON decreased significantly, from 36% to 7%, when the duration of
      dexamethasone exposure during the delayed-intensification phase was shortened
      from 3 to 4 weeks to 2 weeks with a taper (P = .001). CONCLUSION: ON as
      determined by MRI was found to be a common complication in children and
      adolescents after treatment with the Nordic ALL protocols. Revision of the ALL
      protocols by shortening the single exposure to dexamethasone has diminished the
      risk for ON remarkably. High BMI was identified as a new significant risk factor
      for ON.

PMID- 17442992
TI  - Phase I trial and pharmacokinetic study of pemetrexed in children with refractory
      solid tumors: the Children's Oncology Group.
AB  - PURPOSE: We report results of a phase I trial and pharmacokinetic study of
      pemetrexed (LY231514) in children and adolescents with refractory solid tumors.
      Pemetrexed is a novel antifolate that inhibits multiple enzymes necessary for the
      biosynthesis of thymidine and purine nucleotides. The purpose of this study was
      to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs),
      and pharmacokinetic properties of pemetrexed in children. PATIENTS AND METHODS:
      Pemetrexed was administered as a 10-minute intravenous infusion every 21 days.
      Patients received vitamin B12 and folic acid supplementation as well as
      dexamethasone prophylaxis. Cohorts of three to six children were enrolled at dose
      levels of 400, 520, 670, 870, 1,130, 1,470, 1,910, and 2,480 mg/m2.
      Pharmacokinetic studies were performed during the first course of treatment.
      RESULTS: Thirty-three patients (31 assessable) with a median age of 12 years were
      enrolled. DLT occurred in one of six patients at 1,470 mg/m2 and two of four
      patients at 2,480 mg/m2. The MTD was 1,910 mg/m2. The primary DLTs were
      neutropenia and rash. No objective antitumor responses were seen. Mean plasma
      clearance, half-life, and steady-state volume of distribution values were 2.3
      L/h/m2, 2.5 hours, and 5.4 L/m2, respectively. CONCLUSION: Pemetrexed is well
      tolerated in children with refractory solid tumors at doses similar to the MTD in
      adults. The recommended dose for phase II studies is 1,910 mg/m2 administered
      every 21 days with dexamethasone, folic acid, and vitamin B12 supplementation.

PMID- 17442993
TI  - Phase I Trial of G3139, a bcl-2 antisense oligonucleotide, combined with
      doxorubicin and cyclophosphamide in children with relapsed solid tumors: a
      Children's Oncology Group Study.
AB  - PURPOSE: To determine the maximum-tolerated dose, toxicity, pharmacokinetics, and
      biologic effects of G3139 when administered with doxorubicin and cyclophosphamide
      to children with relapsed solid tumors. PATIENTS AND METHODS: Patients received a
      7-day continuous infusion of 3, 5, or 7 mg/kg/d of G3139 every 21 days.
      Doxorubicin, cyclophosphamide, and dexrazoxane were administered on days 5 and 6
      of the infusion. Pharmacokinetics and biology studies were performed during the
      first course. RESULTS: Thirty-seven patients, median age 14 years (range, 1 to 19
      years), were enrolled, of whom 29 were fully assessable for toxicity. Because of
      dose-limiting neutropenia, doses of doxorubicin 30 mg/m2/d for 2 days,
      dexrazoxane 300 mg/m2/d for 2 days, and cyclophosphamide 500 mg/m2/d for 2 days
      were reduced initially, but with the addition of granulocyte colony-stimulating
      factor (GCSF), could be re-escalated to starting doses. At the 7 mg/kg/d dose
      level, only one of six patients experienced DLT (neutropenia > 7 days). At this
      dose, the average (+/- standard deviation) steady-state G3139 concentration was
      2.04 +/- 1 microg/mL, a concentration associated with biologic activity. Eleven
      of 15 patients had reduced bcl-2 expression in peripheral-blood mononuclear cells
      at the first assessable time point of G3139 exposure, and in eight of 14 patients
      with serial specimens this reduction persisted through day 6. CONCLUSION: The
      recommended phase II dose of G3139 is 7 mg/kg/d as a 7-day continuous infusion,
      with cyclophosphamide 500 mg/m2/d and doxorubicin 30 mg/m2/d on days 5 and 6,
      followed by GCSF. G3139 may accentuate the myelosuppressive effects of
      doxorubicin and cyclophosphamide. Evidence for biologic effects of G3139 was
      demonstrated.

PMID- 17442994
TI  - Thromboembolic events in children and young adults with pediatric sarcoma.
AB  - PURPOSE: Adults with malignancy are at increased risk for venous thromboembolic
      events (TEs). However, data in children and young adults with cancer are limited.
      PATIENTS AND METHODS: To determine the risk and clinical features of TEs in
      children and young adults with sarcoma, we reviewed records on 122 consecutive
      patients with sarcoma treated from October 1980 to July 2002. RESULTS: Twenty
      three TEs were diagnosed in 19 of 122 (16%; 95% CI, 10% to 23%) patients.
      Prevalence by diagnosis was Ewing sarcoma, eight of 61 (13%); osteosarcoma, two
      of 20 (10%); rhabdomyosarcoma, four of 26 (15%); and other sarcomas, five of 15
      (33%). TEs developed in 23% of patients with metastases at presentation versus
      10% with localized disease (odds ratio, 2.59; 95% CI, 0.9 to 7.1; P < .06). Fifty
      three percent of patients with thrombosis had a clot at presentation. A lupus
      anticoagulant was detected in four of five evaluated patients. There was a single
      fatality due to pulmonary embolism. Patients who were diagnosed with cancer after
      1993 had a higher rate of TE (7% v 23%; P < .015). Of the 23 events, 43% were
      asymptomatic. Main sites of thromboses were deep veins of the extremities (10 of
      23; 43%), pulmonary embolism (five of 23; 22%), and the inferior vena cava (four
      of 23; 17%). TEs were associated with tumor compression in eight of 23 (35%) and
      with venous catheters in three of 23 (13%). CONCLUSION: Thromboembolism is common
      in pediatric patients with sarcomas. Thromboses are detected frequently around
      the time of oncologic presentation, may be asymptomatic, and seem to be
      associated with a higher disease burden. Children and young adults with sarcoma
      should be monitored closely for thrombosis.

PMID- 17442995
TI  - Femoral head osteonecrosis in pediatric and young adult patients with leukemia or
      lymphoma.
AB  - PURPOSE: Osteonecrosis of the capital femoral epiphysis is a significant late
      toxicity of treatment for childhood leukemia and lymphoma. We determined clinical
      and imaging risk factors predicting clinical joint outcomes of femoral head
      osteonecrosis in pediatric patients with leukemia or lymphoma. PATIENTS AND
      METHODS: We reviewed retrospectively medical records and magnetic resonance
      imaging scans of 80 patients with osteonecrosis of the capital femoral epiphysis.
      Logistic regression was used to examine relationships between risk factors and
      outcomes of joint surface collapse and arthroplasty. We used Kaplan-Meier
      survival curves to display the time to joint surface collapse and arthroplasty
      based on selected predictors. RESULTS: Median time between primary diagnosis and
      diagnosis of osteonecrosis of the hip was 1.7 years (range, 0.1 to 17.5 years).
      Twenty-three patients (29%) underwent arthroplasty in 36 hips at a mean of 1.3
      years (range, 0.5 to 8.6 years) after diagnosis of osteonecrosis. Median age at
      time of first arthroplasty was 20.1 years (range, 15.1 to 35.4 years). Joint
      outcome of osteonecrosis was predicted solely by lesion size at diagnosis of
      osteonecrosis. The worst prognosis was associated with lesions occupying more
      than 30% of the femoral head volume; 80% of hips with these lesions collapsed
      within 2 years of diagnosis and 50% required arthroplasty. CONCLUSION: Lesion
      size of osteonecrosis is the best predictor of clinical joint outcome of hip
      osteonecrosis in survivors of pediatric hematologic malignancy. Lesions occupying
      more than 30% of the femoral head have high likelihood of joint deterioration
      necessitating arthroplasty at a young age.

PMID- 17442996
TI  - Survival and late mortality in long-term survivors of pediatric CNS tumors.
AB  - PURPOSE: To describe the pattern of survival and late mortality among
      contemporary long-term survivors of pediatric CNS tumor. PATIENTS AND METHODS:
      The study population comprised 643 pediatric patients with primary CNS tumor
      treated at St Jude Children's Research Hospital (Memphis, TN) from 1985 to 2000
      who survived > or = 5 years from diagnosis. Patients were classified according to
      primary tumor type, location of tumor, and survival. Cause of death was obtained
      from the medical record and categorized as progression, malignant transformation,
      second malignancy, medical complication, or external cause. RESULTS: Overall
      survival estimates for patients who survived at least 5 years postdiagnosis was
      91.3% +/- 2% and 86% +/- 3% at 10 and 15 years postdiagnosis, respectively. A
      significant difference in the survival rates according to original tumor type (P
      = .001) was seen. Sixty-six (10%) of 643 patients experienced late mortality: 38
      patients (58%) died of progressive disease while 14 patients (21%) died of second
      malignant tumor. Twelve patients (18%), predominantly with diencephalic tumor
      location, died of a specific medical cause: cardiovascular disease (n = 2),
      cerebrovascular accident (n = 1), metabolic collapse and/or sepsis (n = 7),
      respiratory failure (n = 1), or shunt malfunction (n = 1). CONCLUSION: Late
      mortality occurs in a substantial number of long-term survivors of pediatric CNS
      tumors and is most influenced by the initial tumor histopathology. Progressive
      disease remains the most common cause of death within the first decade of
      diagnosis. Teenage patients requiring treatment for panhypopituitarism may be
      especially vulnerable and deserve significant medical surveillance.

PMID- 17442997
TI  - Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin
      (FOLFOX4) for previously treated metastatic colorectal cancer: results from the
      Eastern Cooperative Oncology Group Study E3200.
AB  - PURPOSE: Colorectal cancer is the second leading cause of cancer mortality in the
      United States. Antiangiogenic therapy with bevacizumab combined with chemotherapy
      improves survival in previously untreated metastatic colorectal cancer. This
      study was conducted to determine the effect of bevacizumab (at 10 mg/kg) on
      survival duration for oxaliplatin-based chemotherapy in patients with previously
      treated metastatic colorectal cancer. PATIENTS AND METHODS: Eight hundred twenty
      nine metastatic colorectal cancer patients previously treated with a
      fluoropyrimidine and irinotecan were randomly assigned to one of three treatment
      groups: oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) with bevacizumab;
      FOLFOX4 without bevacizumab; or bevacizumab alone. The primary end point was
      overall survival, with additional determinations of progression-free survival,
      response, and toxicity. RESULTS: The median duration of survival for the group
      treated with FOLFOX4 and bevacizumab was 12.9 months compared with 10.8 months
      for the group treated with FOLFOX4 alone (corresponding hazard ratio for death =
      0.75; P = .0011), and 10.2 months for those treated with bevacizumab alone. The
      median progression-free survival for the group treated with FOLFOX4 in
      combination with bevacizumab was 7.3 months, compared with 4.7 months for the
      group treated with FOLFOX4 alone (corresponding hazard ratio for progression =
      0.61; P < .0001), and 2.7 months for those treated with bevacizumab alone. The
      corresponding overall response rates were 22.7%, 8.6%, and 3.3%, respectively (P
      < .0001 for FOLFOX4 with bevacizumab v FOLFOX4 comparison). Bevacizumab was
      associated with hypertension, bleeding, and vomiting. CONCLUSION: The addition of
      bevacizumab to oxaliplatin, fluorouracil, and leucovorin improves survival
      duration for patients with previously treated metastatic colorectal.

PMID- 17442998
TI  - Phase III study of erlotinib in combination with cisplatin and gemcitabine in
      advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial.
AB  - PURPOSE: Erlotinib is a potent inhibitor of the epidermal growth factor receptor
      tyrosine kinase, with single-agent antitumor activity. Preclinically, erlotinib
      enhanced the cytotoxicity of chemotherapy. This phase III, randomized, double
      blind, placebo-controlled, multicenter trial evaluated the efficacy and safety of
      erlotinib in combination with cisplatin and gemcitabine as first-line treatment
      for advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients
      received erlotinib (150 mg/d) or placebo, combined with up to six 21-day cycles
      of chemotherapy (gemcitabine 1,250 mg/m2 on days 1 and 8 and cisplatin 80 mg/m2
      on day 1). The primary end point was overall survival (OS). Secondary end points
      included time to disease progression (TTP), response rate (RR), duration of
      response, and quality of life (QoL). RESULTS: A total of 1,172 patients were
      enrolled. Baseline demographic and disease characteristics were well balanced.
      There were no differences in OS (hazard ratio, 1.06; median, 43 v 44.1 weeks for
      erlotinib and placebo groups, respectively), TTP, RR, or QoL between treatment
      arms. In a small group of patients who had never smoked, OS and progression-free
      survival were increased in the erlotinib group; no other subgroups were found
      more likely to benefit. Erlotinib with chemotherapy was generally well tolerated;
      incidence of adverse events was similar between arms, except for an increase in
      rash and diarrhea with erlotinib (generally mild). CONCLUSION: Erlotinib with
      concurrent cisplatin and gemcitabine showed no survival benefit compared with
      chemotherapy alone in patients with chemotherapy-naive advanced NSCLC.

PMID- 17442999
TI  - Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute
      of Canada and Intergroup Study JBR.10.
AB  - PURPOSE: Recent trials have shown significant survival benefit from adjuvant
      chemotherapy for non-small-cell lung cancer (NSCLC). Whether elderly patients
      tolerate platinum-based adjuvant chemotherapy and derive the same survival
      advantage is unknown. This retrospective study evaluated the influence of age on
      survival, adjuvant chemotherapy delivery, and toxicity in National Cancer
      Institute of Canada (NCIC) Clinical Trials Group study JBR.10. PATIENTS AND
      METHODS: Pretreatment characteristics and survival were compared for 327 young (<
      or = 65 years) and 155 elderly (> 65 years) patients. Chemotherapy delivery and
      toxicity were compared for 213 treated patients (63 elderly, 150 young). RESULTS:
      Baseline demographics by age were similar with the exception of histology
      (adenocarcinoma: 58% young, 43% elderly; squamous: 32% young, 49% elderly; P =
      .001) and performance status (PS; PS 0: 53% young, 41% elderly; P = .01).
      Chemotherapy significantly prolonged overall survival for elderly patients
      (hazard ratio, 0.61; 95% CI, 0.38 to 0.98; P = .04). This benefit is similar to
      the effect for all patients in JBR.10. Mean dose-intensities of vinorelbine and
      cisplatin were 13.2 and 18.0 mg/m2/wk in young, respectively, and 9.9 and 14.1
      mg/m2/wk in elderly patients (vinorelbine, P = .0004; cisplatin, P = .001),
      respectively. The elderly received significantly fewer doses of vinorelbine (P =
      .014) and cisplatin (P = .006). Fewer elderly patients completed treatment and
      more refused treatment (P = .03). There were no significant differences in
      toxicities, hospitalization, or treatment-related death by age group. Fifteen
      (11.9%) of 126 deaths in the young resulted from nonmalignant causes, and 15
      (21.1%) of 71 in the elderly (P = .13). CONCLUSION: Despite elderly patients'
      receiving less chemotherapy, adjuvant vinorelbine and cisplatin improves survival
      in patients older than 65 years with acceptable toxicity. Adjuvant chemotherapy
      should not be withheld from elderly patients.

PMID- 17443000
TI  - Pretreatment levels of peripheral neutrophils and leukocytes as independent
      predictors of overall survival in patients with American Joint Committee on
      Cancer Stage IV Melanoma: results of the EORTC 18951 Biochemotherapy Trial.
AB  - PURPOSE: An elevated count of blood neutrophils and monocytes recently was shown
      independently to predict short survival in patients with stage IV melanoma
      undergoing interleukin-2-based immunotherapy. In this study, we aimed to validate
      this finding in a large cohort of stage IV melanoma patients. PATIENTS AND
      METHODS: For this retrospective prognostic study, the data from the European
      Organisation for the Research and Treatment of Cancer 18951 study were used.
      Patients were randomly assigned between treatment with dacarbazine, cisplatin,
      and interferon alfa with or without interleukin-2. Counts of neutrophils and
      leukocytes were analyzed together with other known prognostic factors: serum
      lactate dehydrogenase, performance status, metastatic site, and sex. Two
      multivariate prognostic factor analyses were carried out in the model: one with
      leukocyte counts and one with neutrophil counts. RESULTS: A total of 363 patients
      were randomly assigned and baseline blood neutrophil and leukocyte counts were
      available from 316 and 350 patients, respectively. A high neutrophil count (> 7.5
      x 10(9)/L) was an independent prognostic factor for short overall survival
      (hazard ratio [HR], 1.5; 95% CI, 1.1 to 2.1; P = 0.02), and a high leukocyte
      count (> 10 x 10(9)/L) was an independent prognostic factor of both short overall
      survival (HR, 1.7; 95% CI, 1.3 to 2.4; P = 0.0005) and short progression-free
      survival (HR, 1.5; 95% CI, 1.1 to 2.1; P = 0.008). CONCLUSION: A high
      pretreatment count of neutrophils in blood was confirmed as an independent
      prognostic factor for short overall survival in stage IV melanoma patients
      undergoing interleukin-2-based immunotherapy. Furthermore, a high count of
      leukocytes was an independent prognostic factor for short overall survival and
      progression-free survival. Both parameters should be useful as stratification
      factors in clinical trials.

PMID- 17443001
TI  - Sentinel lymph node molecular ultrastaging in patients with melanoma: a
      systematic review and meta-analysis of prognosis.
AB  - PURPOSE: Molecular biology-based ultrastaging of cancer is already part of the
      standard management of patients with hematologic malignancies, whereas the
      evidence for solid tumors is much more debated. Polymerase chain reaction (PCR) 
      based detection of melanoma cells in sentinel lymph nodes (SLN) of patients with
      melanoma represents an appealing prognostic tool. However, no consensus exists on
      the clinical implementation of this prognostic indicator for the management of
      these patients. METHODS: Twenty-two studies enrolling 4,019 patients who
      underwent SLN biopsy for clinical stage I to II cutaneous melanoma were reviewed.
      Correlation of PCR status with TNM stage, disease recurrence rates, and survival
      was assessed by means of association statistics and formal meta-analysis,
      respectively. RESULTS: PCR status correlated with both TNM stage (stage I to II v
      III; PCR positivity, 95.1% v 46.6%; P < .0001) and disease recurrence (PCR
      positive v negative; relapse rate, 16.8% v 8.7%; P < .0001). PCR positivity was
      also associated with worse overall (hazard ratio [HR], 5.08; 95% CI, 1.83 to
      14.08; P = .002) and disease-free (HR, 3.41; 95% CI, 1.86 to 6.24; P < .0001)
      survival. Statistical heterogeneity was significant, underscoring the variability
      among overall effect estimates across studies; metaregression and subgroup
      analysis did not identify clear-cut sources of heterogeneity, although some study
      design variables were suggested as potential causes. CONCLUSION: PCR status of
      SLN appears to have a clinically valuable prognostic power in patients with
      melanoma. Although the heterogeneity of the studies so far published warrants
      caution to avoid overestimating the favorable results of pooled data, our
      findings strongly support additional investigation in this field.

PMID- 17443002
TI  - Toward a molecular classification of melanoma.
AB  - The incidence of melanoma is increasing at one of the highest rates of any form
      of cancer in the United States, with the current lifetime risk being one in 68.
      At present, there are limited systemic therapies to treat advanced stages of
      melanoma, and the key to improved survival remains early detection. Recent
      discoveries have allowed for a clearer picture of the molecular events leading to
      melanoma development and progression. Since identifying prevalent activating
      mutations of the BRAF kinase in melanomas, there has been a flood of additional
      molecular studies to further clarify the role of this pathway and others in
      melanomagenesis. In particular, recent genetic studies have demonstrated specific
      genotype-phenotype correlations that provide the first major insights into the
      molecular subclassification of melanoma and the heterogeneous nature of this
      malignancy. In this article, we review the most up-to-date molecular discoveries
      in melanoma biology and provide a framework for understanding their significance
      in melanoma development and progression. We also provide details on the
      development of novel therapies based on these recent molecular discoveries and
      insight into current and planned clinical trials. It is expected that these
      latest studies in melanoma will help define the critical molecular events
      involved in disease onset and progression and allow us to move rapidly toward a
      true molecular classification. We eagerly anticipate rationally designed melanoma
      therapies based on such a classification scheme and the associated improvements
      in patient outcomes.

PMID- 17443003
TI  - Radiation-induced sarcoma after high-dose thoracic radiation therapy in non-small
      cell lung cancer.

PMID- 17443004
TI  - Pneumatosis coli after etoposide chemotherapy for breast cancer.

PMID- 17443005
TI  - Acquired hypertrichosis lanuginosa: a rare cutaneous paraneoplastic syndrome.

PMID- 17443006
TI  - Problems in identifying functional erythropoietin receptors in cancer tissue.

PMID- 17443007
TI  - Insulin resistance and cancer-related mortality.

PMID- 17443008
TI  - Assessment of the effect of chemotherapy on ovarian function in women with breast
      cancer.

PMID- 17443009
TI  - Improving the institutional submission and approval process for clinical research
      protocols in oncology.

PMID- 17443010
TI  - Barriers to clinical trials vary according to the type of trial and the
      institution.

PMID- 17443011
TI  - Grinding up wheat: a massive loss of nucleotide diversity since domestication.
AB  - Several demographic and selective events occurred during the domestication of
      wheat from the allotetraploid wild emmer (Triticum turgidum ssp. dicoccoides).
      Cultivated wheat has since been affected by other historical events. We analyzed
      nucleotide diversity at 21 loci in a sample of 101 individuals representing 4
      taxa corresponding to representative steps in the recent evolution of wheat
      (wild, domesticated, cultivated durum, and bread wheats) to unravel the
      evolutionary history of cultivated wheats and to quantify its impact on genetic
      diversity. Sequence relationships are consistent with a single domestication
      event and identify 2 genetically different groups of bread wheat. The wild group
      is not highly polymorphic, with only 212 polymorphic sites among the 21,720 bp
      sequenced, and, during domestication, diversity was further reduced in cultivated
      forms--by 69% in bread wheat and 84% in durum wheat--with considerable
      differences between loci, some retaining no polymorphism at all. Coalescent
      simulations were performed and compared with our data to estimate the intensity
      of the bottlenecks associated with domestication and subsequent selection. Based
      on our 21-locus analysis, the average intensity of domestication bottleneck was
      estimated at about 3--giving a population size for the domesticated form about
      one third that of wild dicoccoides. The most severe bottleneck, with an intensity
      of about 6, occurred in the evolution of durum wheat. We investigated whether
      some of the genes departed from the empirical distribution of most loci,
      suggesting that they might have been selected during domestication or breeding.
      We detected a departure from the null model of demographic bottleneck for the
      hypothetical gene HgA. However, the atypical pattern of polymorphism at this
      locus might reveal selection on the linked locus Gsp1A, which may affect grain
      softness--an important trait for end-use quality in wheat.

PMID- 17443012
TI  - Evolution of the glucose-6-phosphate isomerase: the plasticity of primary
      metabolism in photosynthetic eukaryotes.
AB  - Glucose-6-phosphate isomerase (GPI) has an essential function in both catabolic
      glycolysis and anabolic gluconeogenesis and is universally distributed among
      Eukaryotes, Bacteria, and some Archaea. In addition to the cytosolic GPI, land
      plant chloroplasts harbor a nuclear encoded isoenzyme of cyanobacterial origin
      that is indispensable for the oxidative pentose phosphate pathway (OPPP) and
      plastid starch accumulation. We established 12 new GPI sequences from
      rhodophytes, the glaucophyte Cyanophora paradoxa, a ciliate, and all orders of
      complex algae with red plastids (haptophytes, diatoms, cryptophytes, and
      dinoflagellates). Our comprehensive phylogenies do not support previous GPI-based
      speculations about a eukaryote-to-prokaryote horizontal gene transfer from
      metazoa to gamma-proteobacteria. The evolution of cytosolic GPI is largely in
      agreement with small subunit analyses, which indicates that it is a specific
      marker of the host cell. A distinct subtree comprising alveolates (ciliates,
      apicomplexa, Perkinsus, and dinoflagellates), stramenopiles (diatoms and
      Phytophthora [oomycete]), and Plantae (green plants, rhodophytes, and Cyanophora)
      might suggest a common origin of these superensembles. Finally, in contrast to
      land plants where the plastid GPI is of cyanobacterial origin, chlorophytes and
      rhodophytes independently recruited a duplicate of the cytosolic GPI that
      subsequently acquired a transit peptide for plastid import. A secondary loss of
      the cytosolic isoenzyme and the plastid localization of the single GPI in
      chlorophycean green algae is compatible with physiological studies. Our findings
      reveal the fundamental importance of the plastid OPPP for Plantae and document
      the plasticity of primary metabolism.

PMID- 17443013
TI  - Socioeconomic status at birth is associated with risk of schizophrenia:
      population-based multilevel study.
AB  - BACKGROUND: Inconsistent findings obscure understanding the relationship between
      socioeconomic status (SES) and schizophrenia. The aim of the current study was to
      test the association between individual and community SES at birth and risk of
      schizophrenia. METHOD: Population-based longitudinal follow forward study of a 13
      year birth cohort (n = 71 165). Effects of individual and community socioeconomic
      variables were examined using multilevel regression in MLwiN. RESULTS: Years of
      education of fathers and mothers, respectively, (0-8 vs 13+ odds ratio [OR] =
      1.17, P < .0001; OR = 1.14, P < .001) lower occupational status of fathers (OR =
      1.29, P = .036), and poorer residential area SES (OR = 1.26, P = .012) were risk
      factors for schizophrenia. CONCLUSIONS: Individual- and community-level SES at
      the time of birth are associated with an increased risk of schizophrenia.

PMID- 17443014
TI  - The colour of creation: Gertrude Jekyll and the art of flowers.
AB  - Flowers were central to the life and work of Gertrude Jekyll (1843-1932), one of
      the 20th century's most influential garden designers. Born of parents with
      interests across a broad range of the art-science spectrum, Miss Jekyll developed
      an early interest in many arts and crafts, including painting and gardening in
      particular. During her course at the Central School of Design in Kensington she
      studied closely the work of JMW Turner. Many of the compositional elements of
      Turner's paintings, especially his use of colour, can be seen in Miss Jekyll's
      subsequent designs for c. 250 gardens. The use of blue and yellow flowers to
      create a sense of light, and the contrast of cool blue flowers and grey foliage
      with vivid reds and oranges are recurrent themes in her planting schemes, but
      many other aspects of her designs also reflect her broad interest in the art,
      craft, and science of plant cultivation. She encouraged others to seek the
      satisfaction offered by gardening as an art, convinced that a life spent seeking
      perfection would gradually yield 'the power of intelligent combination, the
      nearest thing we can know to the mighty force of creation'. 

PMID- 17443015
TI  - A model describing cell polyploidization in tissues of growing fruit as related
      to cessation of cell proliferation.
AB  - Endoreduplication is a phenomenon, widespread among plants, which consists of an
      incomplete cell cycle without mitosis and leads to the increase of the nuclear
      DNA content. In this work, a model was developed describing cell proliferation
      and DNA endoreduplication over the whole fruit development, from the pre-anthesis
      period until maturation. In each mitotic cycle of duration tau, the proportion of
      cells proceeding through division depends on a constant parameter rho and on the
      progressive decline of the proliferating capacity . The non-dividing cells may
      either stop the reduplication fully, or switch to repeated syntheses of DNA
      without cell division, resulting in cell endoreduplication. A single constant
      parameter sigma describes the proportion of cells that moves from one to the next
      class of DNA content after each lapse of time tauE, considered to be the minimum
      time required for an endocycle. The model calculates the total number of cells
      and their distribution among eight classes of ploidy level. The dynamic patterns
      of cell proliferation and ploidy were compared with those obtained experimentally
      on two contrasting tomato genotypes. The approach developed in this model should
      allow the future integration of new knowledge concerning the genetic and
      environmental control of the switch from complete to incomplete cell cycle.

PMID- 17443016
TI  - Whole-tree level water balance and its implications on stomatal oscillations in
      orange trees [Citrus sinensis (L.) Osbeck] under natural climatic conditions.
AB  - Sustained cyclic oscillations in stomatal conductance, leaf water potential, and
      sap flow were observed in young orange trees growing under natural conditions.
      The oscillations had an average period of approximately 70 min. Water uptake by
      the roots and loss by the leaves was characterized by large time lags which led
      to imbalances between water supply and demand in the leaves. The bulk of the lag
      in response between stomatal movements and the upstream water balance resided
      downstream of the branch, with branch level sap flow lagging behind the stomatal
      conductance by approximately 20 min while the stem sap flow had a much shorter
      time lag of only 5 min behind the branch sap flow. This imbalance between water
      uptake and loss caused transient changes in internal water deficits which were
      closely correlated to the dynamics of the leaf water potential. The hydraulic
      resistance of the whole tree fluctuated throughout the day, suggesting transient
      changes in the efficiency of water supply to the leaves. A simple whole-tree
      water balance model was applied to describe the dynamics of water transport in
      the young orange trees, and typical values of the hydraulic parameters of the
      transpiration stream were estimated. In addition to the hydro-passive stomatal
      movements, whole-tree water balance appears to be an important factor in the
      generation of stomatal oscillations.

PMID- 17443017
TI  - Proteomic analysis reveals differences between Vitis vinifera L. cv. Chardonnay
      and cv. Cabernet Sauvignon and their responses to water deficit and salinity.
AB  - The impact of water deficit and salt stress on two important wine grape
      cultivars, Chardonnay and Cabernet Sauvignon, was investigated. Plants were
      exposed to increasing salinity and water deficit stress over a 16 d time period.
      Measurements of stem water potentials, and shoot and leaf lengths indicated that
      Chardonnay was more tolerant to these stresses than Cabernet Sauvignon. Shoot
      tips were harvested every 8 d for proteomic analysis using a trichloroacetic
      acid/acetone extraction protocol and two-dimensional gel electrophoresis.
      Proteins were stained with Coomassie Brilliant Blue, quantified, and then 191
      unique proteins were identified using matrix-assisted laser desorption ionization
      time of flight/time of flight mass spectrometry. Peptide sequences were matched
      against both the NCBI nr and TIGR Vitis expressed sequence tag (EST) databases
      that had been implemented with all public Vitis sequences. Approximately 44% of
      the protein isoforms could be identified. Analysis of variance indicated that
      varietal difference was the main source of protein expression variation (40%). In
      stressed plants, reduction of the amount of proteins involved with
      photosynthesis, protein synthesis, and protein destination was correlated with
      the inhibition of shoot elongation. Many of the proteins up-regulated in
      Chardonnay were of unclassified or of unknown function, whereas proteins
      specifically up-regulated in Cabernet Sauvignon were involved in protein
      metabolism.

PMID- 17443019
TI  - Alteration of interneuron migration in a ferret model of cortical dysplasia.
AB  - During cerebral cortical development, gamma-aminobutyric acidergic (GABAergic)
      interneurons arise from a different site than projection neurons. GABAergic cells
      are generated in the subpallial ganglionic eminence (GE), while excitatory
      projection neurons arise from the neocortical ventricular zone. Our laboratory
      studies a model of cortical dysplasia that displays specific disruption of
      GABAergic mechanisms and an alteration in the overall balance of excitation in
      the neocortex. To produce this model, the birth of neurons on a specific
      gestational day in ferrets (embryonic day 33 [E33]) is interrupted by injection
      of the antimitotic methylazoxymethanol (MAM). We hypothesized that migration of
      interneurons might be disrupted in this cortical dysplasia paradigm. We observed
      that although interneurons migrate into the neocortex in both normal and
      dysplastic cortex, the migrating cells become disoriented over time after E33 MAM
      treatment. Coculture experiments using normal GE and MAM-treated cortex (and vice
      versa) demonstrate that cues dictating proper orientation of migrating
      interneurons arise from the cortex and are not intrinsic to the migrating cells.
      As a consequence, interneurons in mature brains of MAM-treated animals are
      abnormally distributed. We report that GABA(A) receptor activation is crucial to
      the proper positioning of interneurons migrating into the cortex from the GE in
      normal and MAM-treated animals.

PMID- 17443018
TI  - Abnormal cortical thickness and brain-behavior correlation patterns in
      individuals with heavy prenatal alcohol exposure.
AB  - Quantitative magnetic resonance imaging (MRI) studies in children with fetal
      alcohol spectrum disorders (FASDs) have shown regional patterns of dysmorphology,
      most prominent in parietal and posterior temporal cortices. Various methods of
      image analysis have been employed in these studies, but abnormalities in cortical
      thickness have not yet been mapped over the entire cortical surface in
      individuals with FASD. Further, relationships between cognitive dysfunction and
      cortical thickness measures have not yet been explored. We applied cortical
      pattern matching algorithms and techniques for measuring cortical thickness in
      millimeters to the structural brain MRI images of 21 subjects with heavy prenatal
      alcohol exposure (8-22 years, mean age 12.6 years), and 21 normally developing
      control subjects (8-25 years, mean age 13.5 years). Dissociable cognitive
      measures, of verbal recall and visuospatial functioning, were correlated with
      cortical thickness, and group by test score interactions were evaluated for
      predicting cortical thickness. Significant cortical thickness excesses of up to
      1.2 mm were observed in the FASD subjects in large areas of bilateral temporal,
      bilateral inferior parietal, and right frontal regions. Significant group by test
      score interactions were found in right dorsal frontal regions for the verbal
      recall measure and in left occipital regions for the visuospatial measure. These
      results are consistent with earlier analyses from our own and other research
      groups, but for the first time, we show that cortical thickness is also increased
      in right lateral frontal regions in children with prenatal alcohol exposure.
      Further, the significant interactions show for the first time that brain-behavior
      relationships are altered as a function of heavy prenatal alcohol exposure.

PMID- 17443020
TI  - Re: "Meta- and pooled analysis of GSTT1 and lung cancer: a HuGE-GSEC review".

PMID- 17443021
TI  - Fetal growth and acute childhood leukemia: looking beyond birth weight.
AB  - The authors examined the relation between birth weight, intrauterine growth, and
      risk of childhood leukemia using population-based linked health data from Western
      Australia. A cohort of 576,593 infants born in 1980-2004 were followed from birth
      to diagnosis of acute lymphoblastic leukemia (ALL) (n = 243) or acute myeloid
      leukemia (AML) (n = 36) before their 15th birthday, death, or the end of follow
      up (December 31, 2005). Data were analyzed using Cox regression. Risk of ALL was
      positively associated with the proportion of optimal birth weight--a measure of
      the appropriateness of fetal growth--particularly among children younger than 5
      years; the hazard ratio for a 1-standard-deviation increase in proportion of
      optimal birth weight was 1.25 (95% confidence interval: 1.07, 1.47). Among
      children younger than 5 years not classified as having high birth weight (defined
      as >3,500 g, >3,800 g, and >4,000 g), a 1-unit increase in proportion of optimal
      birth weight was associated with an approximately 40% increase in ALL risk. This
      suggests that accelerated growth, rather than high birth weight per se, is
      involved in the etiology of ALL. These findings are consistent with a role for
      insulin-like growth factor I in the causal pathway. Findings for AML were
      inconclusive, probably because of small numbers.

PMID- 17443022
TI  - Prediction of coronary heart disease risk using a genetic risk score: the
      Atherosclerosis Risk in Communities Study.
AB  - Recent studies have evaluated whether incorporating nontraditional risk factors
      improves coronary heart disease (CHD) prediction models. This 1986-2001 US study
      aggregated the contribution of multiple single nucleotide polymorphisms into a
      genetic risk score (GRS) and assessed whether the GRS plus traditional risk
      factors predict CHD better than traditional risk factors alone. The
      Atherosclerosis Risk in Communities (ARIC) cohort was followed for a median of 13
      years for CHD events (n = 1,452). Individuals were genotyped for 116 single
      nucleotide polymorphisms associated with CHD in multiple case-control studies.
      Single nucleotide polymorphisms nominally predicting incident CHD in the ARIC
      study were included in the GRS. The GRS was significantly associated with
      incident CHD in Blacks (hazard rate ratio = 1.20, 95% confidence interval: 1.11,
      1.29) and Whites (hazard rate ratio = 1.10, 95% confidence interval: 1.06, 1.14)
      as well as in each tertile defined by the traditional cardiovascular risk score
      (p < or = 0.02). When receiver operating characteristic curves based on
      traditional risk factors were recalculated after the GRS was added, the increase
      in the area under the receiver operating characteristic curve was statistically
      significant for Blacks and suggestive of improved CHD prediction for Whites. This
      study demonstrates the concept of aggregating information from multiple single
      nucleotide polymorphisms into a risk score and indicates that it can improve
      prediction of incident CHD in the ARIC study.

PMID- 17443023
TI  - Serum dioxin concentrations and risk of uterine leiomyoma in the Seveso Women's
      Health Study.
AB  - Uterine leiomyomata (fibroids), benign neoplasms of the smooth muscle, are a
      major cause of hysterectomy. Exposure to hormonally active chemicals may play an
      etiologic role. The authors investigated the risk of uterine leiomyoma associated
      with exposure to 2,3,7,8,-tetrachlorodibenzo-p-dioxin (TCDD) for women who
      resided near Seveso, Italy, in 1976 at the time of a chemical explosion. Twenty
      years later, women enrolled in the Seveso Women's Health Study were asked about
      history of fibroids, medical records were obtained, and vaginal ultrasonography
      was performed for a subset. Serum collected soon after the explosion was analyzed
      for TCDD. A likelihood-based method that combines both historical and current
      status (ultrasound) data was adapted to estimate the hazard ratio. Of 956
      eligible women, 251 (26.3%) had fibroids. Compared with that for women with TCDD
      levels of < or = 20 parts per trillion, the age-adjusted hazard ratios were 0.58
      (95% confidence interval: 0.41, 0.81) for women with levels of 20.1-75.0 parts
      per trillion and 0.62 (95% confidence interval: 0.44, 0.89) for women with levels
      of >75.0 parts per trillion. This finding suggests that TCDD may have
      antiestrogenic effects in the uterine myometrium, in contrast to apparently
      estrogenic effects previously found in the breast of Seveso Women's Health Study
      women.

PMID- 17443024
TI  - Effect of long-term vagal stimulation on food intake and body weight during diet
      induced obesity in rats.
AB  - Regulation of food intake and body weight is accomplished by several mechanisms.
      CNS receives information from periphery and modifies food intake mainly by vagal
      nerves that provide the major neuroanatomical link between gastrointestinal sites
      stimulated during food intake and CNS sites that control feeding behavior and
      metabolism. Gastric mechanoreceptors and jejunal chemoreceptors activated by food
      or vagal nerve stimulation (VNS), which mimic the physiological input, suppress
      feeding within short-term regulation. Our research was aimed on determination the
      role of electrical VNS in long-term control of food intake and body weight in
      diet induced obesity fed rats. Food intake, body weight and epididymal fat pad
      were assessed in male Wistar rats divided into three groups (controls vs. VNS).
      Rats were implanted with microchip and kept during the whole study (100 days) on
      diet induced obesity. Vagal nerve was stimulated by electrical rectangular pulses
      duration 10 ms, amplitude 200 mV, frequency 0.05 Hz generated by microchip. In
      control group surgery produced no significant changes in meal size and body
      weight gain as compared to intact group. In contrast, significantly decreased
      epididymal fat pad weight, decreased meal size with effect on decreased weight
      gain was observed in VNS rats. Data support theory that VNS can increase vagal
      afferent signal conduct to CNS and mimics the satiety signals leading to reduce
      food intake and body weight gain.

PMID- 17443025
TI  - Basal and postprandial plasma levels of PYY, ghrelin, cholecystokinin, gastrin
      and insulin in women with moderate and morbid obesity and metabolic syndrome.
AB  - Metabolic syndrome (MS), defined as central obesity, hyperinsulinemia, insulin
      resistance, hypertension, dyslipidemia and glucose intolerance, has been
      associated with inflammatory biomarkers and cardiovascular diseases. This study
      was carried out on three groups of women; lean controls, moderately obese with MS
      (OB-MS) and morbidly obese with MS (MOB-MS). The main objectives were: 1. to
      analyze the plasma levels of total and acylated ghrelin, peptide YY(3-36) (PYY(3
      36)), cholecystokinin (CCK), gastrin and insulin levels under basal conditions
      and in response to a standard mixed meal, and 2. to elucidate the relationship
      between the plasma levels of these gut peptides and metabolic syndrome
      parameters. Plasma levels of the gut hormones were measured by radioimmunoassays
      at time 0 just before the meal and at 30, 60 and 120 min after a meal ingestion.
      Traditional lipid profile and high-sensitivity C reactive protein (hs-CRP), the
      strongest biomarker of inflammation were also determined in OB-MS and MOB-MS.
      When compared to OB-MS, MOB-MS exhibited much higher anthropometric parameters
      such as waist circumference, higher fat mass and higher plasma levels of low
      density lipoprotein-cholesterol (LDL-C) and hs-CRP. Both these obese groups
      revealed significantly higher values of body mass index (BMI), fat mass, total
      cholesterol (TC), LDL-C, fasting glucose, fasting insulin, insulin resistance
      (IR) calculated from homeostatic model assessment (HOMA) and hs-CRP compared to
      the values recorded in lean subjects. Fasting PYY(3-36) level was lower, while
      fasting acylated ghrelin was higher in MOB-MS than in OB-MS. Plasma total and
      acylated ghrelin levels were significantly lower in OB-MS compared to lean women.
      In MOB-MS women the fasting PYY(3-36) levels were lower compared to lean controls
      and OB-MS, whilst postprandially in both OB-MS and MOB-MS, it was much lower than
      in lean women. The fasting plasma levels of total and acylated ghrelin and their
      postprandial decrease were significantly smaller in both obese groups compared to
      lean subjects. Plasma hs-CRP levels correlated positively with BMI, waist
      circumference, fat mass, fasting glucose, HOMA IR and fasting active ghrelin,
      whilst it negatively correlated with plasma fasting and total ghrelin. Moreover,
      plasma fasting acylated ghrelin correlated positively with fat mass. Fasting
      total ghrelin correlated positively with BMI, HDL-C and negatively with HOMA IR.
      We conclude that MS features of obesity are closely related to fasting and
      postprandial alterations of concentrations of PYY(3-36), CCK and ghrelin,
      suggesting that determination of gut hormones controlling food intake might be
      considered as a valuable tool to assess the progression of MS to comorbidities of
      obesity.

PMID- 17443026
TI  - Basal and postprandial gut peptides affecting food intake in lean and obese
      pregnant women.
AB  - Maternal obesity has been reported as a risk factor for various maternal and
      fetal complications. The aim of the present study was to examine the patterns of
      basal and postprandial plasma concentrations of certain gut hormones affecting
      food intake such as acylated ghrelin, peptide YY(3-36) (PYY(3-36)),
      cholecystokinin (CCK), insulin and glucose in pregnant women with varying body
      mass gain during physiological pregnancy. The study included 34 women with
      singleton pregnancies in the 2(nd) trimester of gestation. The examined pregnant
      women were divided into 4 groups; I. control pregnancy (CP) with weight gain
      below 0.5 kg/week; II. overweight low weight gain <1 kg/week (OLWG), III.
      overweight high weight gain >1 kg/week (OHWG); morbidly obese pregnant with
      weight gain >1.5 kg/week (MOP). The basal acylated-ghrelin levels in MOP subjects
      were significantly higher than those in CP and no usual suppression of acylated
      ghrelin after the meal observed in CP as well as in OLWG and OHWG was found in
      MOP women. Basal PYY(3-36) plasma levels were similar in CP, OLWG and OHWG but in
      MOP was significantly reduced and no significant increase in hormone level,
      typically observed in CP, was detected after a meal in overweight or obese women
      studied. The fasting CCK and C-reactive protein (CRP) levels in MOP subjects were
      significantly higher than those in CP and other overweight women. In conclusion,
      we found that pregnant women with overweight and obesity exhibit significant
      changes in fasting and postprandial gut hormones affecting food intake such as
      acylated ghrelin, PYY(3-36) and CCK as well as in CRP and these changes might
      contribute, at least in part, the development of obesity in pregnancy.

PMID- 17443027
TI  - Role of leptin, ghrelin, angiotensin II and orexins in 3T3 L1 preadipocyte cells
      proliferation and oxidative metabolism.
AB  - There is now growing evidence that the reactive oxygen species have an influence
      on proliferation and antioxidative status of various cell types. The aim of the
      study was to investigate the effects of different concentrations of leptin,
      ghrelin, angiotensin II and orexins on proliferation, culture medium
      malondialdehyde (MDA) levels and antioxidative enzymes activities: superoxide
      dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in 3T3 L1
      preadipocytes cell culture. Cell proliferation was measured using [(3)H]tymidine
      incorporation. In 3T3-L1 cells leptin caused a significant reduction in
      proliferation (by 36%) compared to control. Ghrelin increased preadipocyte
      proliferation, and the effect was stronger in higher dose (by 39%), while
      proproliferatory effect of angiotensin II was stronger in lower doses (by 47%).
      All used doses of orexin A significantly increased 3T3 L1 cell proliferation
      (from 21% to 160%), while orexin B caused a marked reduction (from 35% to 70%) of
      this proliferation. The effects of both orexins were dose-dependent. Leptin and
      ghrelin increased activity of SOD, CAT, GSH-Px and decreased level of MDA.
      Angiotensin II treatment stimulated only SOD and CAT activities. Influence of
      orexins was different on various enzymes. Orexin A increased MDA levels, while
      orexin B caused a marked decrease in MDA levels. Our results strongly suggest the
      effects of appetite affecting hormones such as leptin and ghrelin on
      proliferation and antioxidative enzyme activities of preadipocyte cell lines.
      Orexin A was found to be the most efficient proliferative-signalling hormone,
      while orexin B revealed the most significant inhibitory effect on preadipocytes
      proliferation.

PMID- 17443028
TI  - Adiponectin, resistin and subclinical inflammation--the metabolic burden in
      Launois Bensaude Syndrome, a rare form of obesity.
AB  - The aim of the study was to investigate, whether the degree of metabolic risk
      factors for atherosclerotic complications in a very rare kind of obesity, the
      Multiple Symmetrical Lipomatosis, also known as the Launois-Bensaude Syndrome
      (LBS), are comparable or different from "simple" truncal obesity. 10 patients
      with LBS (Body mass index 34.4 +/- 1.8 kg/m(2), age: 62 +/- 3 yrs) were compared
      with 19 BMI - matched patients with "simple" truncal obesity and obstructive
      sleep apnoea syndrome (OSAS) and 20 BMI- matched patients with "simple" truncal
      obesity without OSAS. Markers of subclinical inflammation and thrombocyte
      activation (sCD62p = soluble p-selectin, highly sensitive C-Reactive protein =
      CRP, Interleukin-6 = IL-6, ICAM-1 = Intracellular Adhesion Molecule-1, Vascular
      Cell Adhesion Molecule = VCAM -1, leptin), as well as adiponectin and resistin
      were studied. The prevalence of atherogenic risk factors as hypertension (80%),
      type 2 diabetes (30%), OSAS (50%), smoking (30%) and alcohol abuse (80%) was high
      in the (obese) LBS group. The markers of subclinical inflammation and thrombocyte
      activation showed an indifferent picture with lower levels of circulating IL-6
      and sCD62p, comparable CRP and higher ICAM-1 and VCAM-1 than in controls. Leptin
      and adiponectin were higher than in controls. However, the accumulation of
      "classic" cardiovascular risk factors in the LBS group was well reflected by the
      presence of symptomatic cardiovascular disease in 3 of the 10 LBS patients,
      putting LBS patients - if obese - at an atherosclerotic risk at least comparable
      to obese persons.

PMID- 17443029
TI  - Sleep apnea syndrome and snoring in patients with hypothyroidism with relation to
      overweight.
AB  - The relation between snoring and obstructive sleep apnea as well as
      hypothyroidism is the object of interest of many authors. The respiratory
      disturbances during sleep are often observed in patients suffering from
      hypothyroidism. The relation of snoring to overweight in those patients has not
      been taken into account. The aim of the study was to evaluate the relations
      between hypothyroidism and quantitative and qualitative respiratory disturbances
      during sleep. Additional aim was to establish the relations of sleep apnea
      syndrome, snoring, hypothyroidism and overweight. The subjects included 15
      patients (11 females and 4 males) aged from 28 to 73 (mean 50.3) suffering from
      hypothyroidism. All of them underwent thyroid testing before and after the
      hormonal treatment. TSH and fT4 concentrations were determined. At the same time
      the sleep assessment (PolyMESAM) was performed twice. Data were obtained from
      sleep studies and questionnaires (Epworth sleepiness scale). After the thyroid
      hormones stabilization significant decrease of snoring severity was observed. On
      the contrary, the respiratory disturbance index (RDI), desaturation index (DI),
      the lowest saturation (LSAT) did not change significantly, however, the Epworth
      scale score showed significant improvement. The correlations showed the strong
      relation between loud snoring and TSH (r=0.73, p<0.01) and fT4 (r=-0.66, p<0.003)
      concentrations before the treatment. The analysis showed no correlation between
      body mass (BMI) and snoring. The hormonal stabilization in patients suffering
      from hypothyroidism causes improvement in snoring severity. Based on our
      investigation the relationship between hypothyroidism and severity of snoring and
      excessive daytime somnolence was confirmed. It indicates a possible connection
      between hypothyroidism and upper airway resistance syndrome.

PMID- 17443030
TI  - A health-economic evaluation of aspirin: primary prevention and cardiovascular
      disease.

PMID- 17443031
TI  - The relationship of salivary gland function to elevated serum IgG4 in autoimmune
      pancreatitis.
AB  - OBJECTIVE: To compare salivary gland function in autoimmune pancreatitis (AIP)
      patients with and without an elevated serum IgG4 concentration. PATIENTS AND
      METHODS: We allocated 14 AIP patients into 2 groups: one group had high (>135
      mg/dL) serum IgG4 and the other low serum IgG4. Sialochemistry and submandibular
      and parotid gland scintigraphy were done in these patients. RESULTS: Serum IgG4
      levels were elevated in 10 patients. Bilateral submandibular gland swelling was
      present in 5 patients with a high serum IgG4; there was no swelling in patients
      with a low serum IgG4. The salivary Na+ concentration was increased significantly
      in both patient groups (p<0.01) compared to controls. The beta2-microglobulin
      concentration was significantly higher in patients with a high serum IgG4 than in
      those with a low serum IgG4 (p<0.05) and controls (p<0.01). On submandibular and
      parotid gland scintigraphy, both the ratio of the cumulative peak count to the
      injected radionuclide (PCR) and the washout ratio (WR) were significantly lower
      in the high serum IgG4 group than in controls (p<0.01). In the low serum IgG4
      group, the PCR on submandibular gland scintigraphy, and the PCR and WR on parotid
      gland scintigraphy were significantly lower than in controls (p<0.05, p<0.01 and
      p<0.05, respectively). On submandibular gland scintigraphy, the PCR was
      significantly lower in the high serum IgG4 group than in the low serum IgG4 group
      (p<0.05). CONCLUSIONS: Salivary gland function was impaired in all AIP patients,
      but it was more impaired in patients with a high serum IgG4 than in those with a
      low serum IgG4.

PMID- 17443032
TI  - Plasma level of thrombomodulin is an early indication of pancreatic necrosis in
      patients with acute pancreatitis.
AB  - BACKGROUND: The potential to predict pancreatic necrosis within the first 48 h by
      using plasma soluble thrombomodulin (sTM) in 104 patients with acute pancreatitis
      (AP) was analyzed in a prospective 5-year investigation performed at a single
      institution. METHODS: According to Balthazar CT grade, pancreatitis was
      classified as no necrosis in 72 patients, one-third necrotic in 18 patients, one
      half necrotic in 10 patients and more than one-half necrotic in 4 patients. Blood
      was collected at the first 48 hours after the onset of pain and analyzed for sTM.
      RESULTS: In the healthy volunteers, plasma levels of TM were 16.49+/-5.24
      microg/L. By comparison, the mean plasma levels of TM in each group of
      pancreatitis patients were as follows: CT grade A group, 34.21+/-10.73 microg/L;
      CT grade B group, 36.18+/-12.50 microg/L; CT grade C group, 49.39+/-18.38
      microg/L; CT grade D group, 114.46+/-39.44 microg/L; CT grade E group, 100.22+/
      15.97 microg/L (p<0.01). And for the patients, the Pearson correlation
      coefficient between the CT grade and TM values was 0.784 (p<0.01). No necrosis
      group, 39.22+/-13.75 microg/L; one-third necrotic group, 71.44+/-18.02 microg/L;
      one-half necrotic group, 123.50+/-28.57 microg/L; more than one-half necrotic
      group, 129.00+/-33.28 microg/L (p<0.01); And for the patients, the Pearson
      correlation coefficient between the degree of necrosis and TM values was 0.888
      (p<0.01). ROC analysis indicated the area under the ROC curve (AUC +/- SE) for
      sTM was 0.949+/-0.020, clearly supportive of the high accuracy of this index in
      predicting the necrosis of AP. CONCLUSION: Plasma soluble thrombomodulin (sTM) is
      a potential marker to predict pancreatic necrosis within the first 48 h, and
      further investigation in a multicentre study is necessary.

PMID- 17443034
TI  - Association between serum adiponectin levels and arteriolosclerosis in IgA
      nephropathy patients.
AB  - OBJECTIVE: Adiponectin has attracted great attention because of its anti
      atherogenic properties; however, to date the relationship between serum
      adiponectin and arteriolosclerosis has not been reported. In our study, we aimed
      to examine whether or not serum adiponectin levels are associated with
      arteriolosclerosis in patients with IgA nephropathy which is the most common form
      of chronic glomerulonephritis. MATERIALS AND METHODS: We enrolled 35 patients
      aged 35.0+/-14.6, who underwent renal biopsy from August 2004 to February 2006 in
      our hospital, and were confirmed to have IgA nephropathy. We examined serum
      adiponectin, high-sensitive C-reactive protein, total cholesterol and
      triglyceride level, urinary protein excretion, body mass index (BMI), and the
      presence of arteriolosclerosis in the renal specimens. Since the serum
      adiponectin level is strongly affected by renal function, we classified the
      patients by creatinine clearance. RESULTS: Multiple regression analysis showed
      the associations of adiponectin with creatinine clearance (p<0.001), BMI
      (p<0.001), serum triglyceride (p=0.001) and urinary protein excretion (p=0.001).
      We observed a positive relation of adiponectin with urinary protein excretion and
      an inverse relation of adiponectin with creatinine clearance, serum triglyceride,
      and BMI. We could not detect any relation between the presence of
      arteriolosclerosis and adiponectin in the IgA nephropathy patients as a whole;
      however, in patients whose creatinine clearance was 90-120 ml/min/1.73 m2, the
      serum adiponectin level of patients with arteriolosclerosis was lower than in
      those without arteriolosclerosis (p=0.025). CONCLUSION: The serum level of
      adiponectin was related to arteriolosclerosis in IgA nephropathy patients whose
      renal function was almost normal. Adiponectin may prevent renal
      arteriolosclerosis.

PMID- 17443033
TI  - Effect of sevelamer hydrochloride on markers of bone turnover in Japanese
      dialysis patients with low biointact PTH levels.
AB  - BACKGROUND: In hemodialysis patients, adynamic bone disease has been reported to
      be closely associated with low levels of parathyroid hormone (PTH) due to
      exposure to high levels of serum calcium following the administration of calcium
      carbonate (CaCO3) or vitamin D agents. This study was conducted to clarify the
      therapeutic effect of a non-calcemic phosphate binder, sevelamer hydrochloride
      (sevelamer), for hypoparathyroidism in hemodialysis patients with or without
      diabetes mellitus. METHODS: Based on entry criteria, 40 Japanese chronic
      hemodialysis patients (22 males and 18 females with a mean age of 60.6, 14
      diabetic patients and 26 non-diabetic patients) were switched from CaCO3 to
      sevelamer for 48 weeks. Serum calcium, phosphate, intact (i) PTH and PTH-(1-84)
      were analyzed. Bone remodeling activity was evaluated by determining intact
      osteocalcine (iOC), bone-specific alkaline phosphatase (BAP). RESULTS: The switch
      from CaCO3 to sevelamer significantly decreased the serum levels of calcium,
      resulting in the elevation of iPTH levels from 31+/-18 pg/mL to 95+/-96 pg/mL by
      48 weeks. In contrast, serum phosphate levels remained similar to those in
      patients with CaCO3 treatment. Concomitantly, the levels of BAP and iOC were
      elevated. Further, these beneficial effects on bone turnover were observed in
      both diabetic and non-diabetic patients. CONCLUSION: Sevelamer reduced the
      calcium concentration and thereby increased PTH levels, resulting in the
      improvement of markers of bone turnover. The administration of sevelamer is of
      therapeutic benefit for the improvement of bone remodeling activity even in
      hemodialysis patients with diabetes.

PMID- 17443035
TI  - Clinical characteristics of 8 sporadic cases of community-acquired Legionella
      pneumonia in advanced age.
AB  - Legionella spp are well recognized as one of the etiologic factor in pneumonia,
      but it is difficult to distinguish the clinical features of Legionella infection
      from pneumonia due to other causes. The objective of the present study was to
      examine the clinical characteristics of community-acquired Legionella pneumonia
      in elderly patients. We reviewed the clinical, laboratory and radiographic
      findings in 8 patients diagnosed as having pneumonia caused by Legionella. The
      diagnosis was confirmed by the presence of urinary antigen, bacterial culture,
      polymerase chain reaction (PCR) and serum antibody. There were 6 men and 2 women,
      whose ages ranged from 76 to 85 years. All patients had fever and hypoxia, four
      patients had respiratory symptoms. The initial chest X-ray findings were varied-
      consolidation, ground glass opacity, pleural effusion and linear shadow. Urinary
      antigen was positive in 4 patients, bacterial culture in 2, PCR on the sputum in
      3 and serum antibody in 2 patients. As pneumonia caused by Legionella often
      becomes life-threatening, especially in elderly people, it is imperative to
      diagnose it at the initial stage. In this study, urinary antigen proved to be the
      most useful diagnostic means. However, it is important to confirm the diagnosis
      through plural examinations.

PMID- 17443036
TI  - Multi-center randomized control trial of etizolam plus NSAID combination for
      tension-type headache.
AB  - OBJECTIVE: Benzodiazepines are commonly used for the treatment of tension-type
      headache (TTH), however, there are few randomized controlled trials recommending
      the use of these drugs in Japan. This study was undertaken to evaluate the
      efficacy of etizolam, a thienodiazepine derivative, in combination with a non
      steroidal anti-inflammatory drug (NSAID) as an acute treatment for TTH. METHODS:
      The study design was a multi-center randomized control trial and included 144
      patients. The diagnosis of TTH was based on the criteria of the International
      Classification of Headache Disorders-1 and all patients were diagnosed with
      episodic tension-type headache (ETTH). Changes in the severity of headache and
      shoulder pain were graded using a Visual Analogue Scale (VAS) before and after
      administration of drugs. Patients were randomized into NSAID alone (NSAID,
      mefenamic acid, 250 mg) group and NSAID (mefenamic acid, 250 mg) plus etizolam
      (0.5 mg) (NSAID-ET) group prior to treatment. RESULTS: Although both groups
      showed a significant drop in VAS for headache and shoulder pain (p<0.01), there
      was no overall significant difference between the NSAID-ET and NSAID groups.
      However, headache was improved significantly in female patients (p<0.05), and
      shoulder pain was improved in young and female patients (p<0.05, p<0.04) in the
      NSAID-ET group. CONCLUSION: This study indicates that the combination treatment
      of etizolam and NSAID is useful in young or female patients.

PMID- 17443038
TI  - Pulmonary embolism and deep vein thrombosis complicating acute aortic dissection
      during medical treatment.
AB  - Acute aortic dissection of Stanford type A with intramural hematoma was diagnosed
      based on computed tomography (CT) findings in a 60-year-old man. During medical
      treatment, pulmonary embolism and deep vein thrombosis developed. CT revealed
      thrombosis in the right pulmonary artery, and 99mTc pulmonary perfusion
      scintigraphy showed defects in the right lung field. CT showed thrombus in the
      common iliac vein. An inferior vena caval filter was placed because
      anticoagulation therapy was contraindicated. A CT scan before discharge showed no
      thrombus in the pulmonary artery or common iliac vein, but a newly captured
      thrombus was found inside the filter.

PMID- 17443037
TI  - Systemic sclerosis after interferon alphacon-1 therapy for hepatitis C.
AB  - A 66-year-old woman developed systemic sclerosis (SSc) after receiving interferon
      alphacon-1 (IFNalphacon-1; consensus interferon) therapy for chronic hepatitis C.
      She suffered from Raynauds phenomenon about 1 year after a course of IFNalphacon
      1 therapy. The combination of proximal scleroderma, Raynauds phenomenon, and ANA
      positivity led to a diagnosis of systemic sclerosis (SSc). IFN has multiple
      effects on the immune system and is known to trigger the development of
      autoantibodies, as well as the onset or exacerbation of autoimmune disease. We
      suspect that the immunomodulatory effects of IFNalphacon-1 triggered the clinical
      manifestations of SSc in this patient. To our knowledge this is only the third
      case of SSc after IFNalpha therapy, and it is the first case associated with
      IFNalphacon-1 therapy.

PMID- 17443039
TI  - Occult gastrointestinal bleeding due to acquired von Willebrand syndrome in a
      patient with hypertrophic obstructive cardiomyopathy.
AB  - A 69-year-old woman presented with a harsh systolic murmur and severe anemia.
      Echocardiography demonstrated hypertrophic obstructive cardiomyopathy with a peak
      pressure gradient of 154 mmHg. Endoscopic examinations disclosed an
      angiodysplasia and multiple diverticula in the colon, but no active bleeding was
      noted in these lesions. A selective defect of large multimers of von Willebrand
      factor was detected by electrophoresis. After collection of anemia and Ca
      antagonist therapy, left ventricular obstruction was relieved and cessation of
      the occult gastrointestinal bleeding was obtained. This is the first report
      whereby acquired type 2A von Willebrand syndrome was caused by hypertrophic
      obstructive cardiomyopathy.

PMID- 17443040
TI  - Leukocytoclastic vasculitis after pneumococcal pneumonia in an elderly adult.
AB  - Hypersensitivity vasculitis (HSV) has been used to describe several forms of
      vasculitis of small blood vessels, including Henoch-Schonlein purpura (HSP),
      mixed cryoglobulinemia, and allergic vasculitis, etc. HSP is a disease
      occasionally seen in childhood, and is characterized by dermatological and
      abdominal symptoms. Here, we report a rare case of HSV which showed a clinical
      course similar to HSP after pneumococcal pneumonia in an elderly adult.
      Generally, Streptococcus pneumoniae is the most common pathogen in adult
      community-acquired pneumonia. Therefore, it is critical to recognize HSV as one
      of the important complications after bacterial infection, especially
      Streptococcus pneumoniae.

PMID- 17443041
TI  - A patient with pulmonary lymphangitic carcinomatosis successfully treated with TS
      1 and cisplatin.
AB  - A 37-year-old man was referred to our hospital with complaints of dyspnea and
      general fatigue. Chest radiograph and CT scan revealed thickness of
      bronchovascular bundles in both lungs. In spite of various examinations, the
      primary lesion was not identified. He received chemotherapy containing TS-1 and
      cisplatin. Pulmonary lymphangitic carcinomatosis disappeared and the patient
      achieved a good partial response. He survived for 14 months after the
      chemotherapy. We believe the combination of TS-1 and cisplatin is one of the
      attractive options for patients with cancer of unknown primary site.

PMID- 17443042
TI  - Hemophagocytic syndrome associated with fatal veno-occlusive disease in the
      liver.
AB  - A 47-year-old man presented with hemophagocytic syndrome (HPS) without any
      obvious underlying diseases. On computed tomography, his liver was occupied by
      multiple ill-defined low intensity lesions. Liver biopsy revealed diffuse
      infiltration of numerous histiocytes without cytologic atypism and prominent
      fibrotic changes. These histiocytes showed S100(+), CD68(+), CD1a(-), and
      lysozyme(+) and Langerhans cell granules were not observed by electron
      microscopic examination. He failed to respond to immunosuppressive and
      chemotherapeutic treatments and progressed to severe liver failure. At autopsy,
      his liver exhibited veno-occlusive disease (VOD). Since VOD is regarded as a rare
      complication of HPS, the presence of VOD associated with HPS may be easily
      overlooked.

PMID- 17443043
TI  - Trigger finger as an initial manifestation of familial amyloid polyneuropathy in
      a patient with Ile107Val TTR.
AB  - We describe a Japanese family with transthyretin Val107-related familial amyloid
      polyneuropathy (FAP). The clinical features were high-aged onset, sensorimotor
      polyneuropathy, carpal tunnel syndrome (CTS) and trigger finger. In addition, the
      proband showed cardiac conduction block and amyloid deposition in the sural nerve
      and dermis. Trigger finger may be a so far unknown clinical manifestation of
      Val107 FAP due to amyloid deposition in the connective tissue like CTS.

PMID- 17443044
TI  - Abnormal brain MRI signals in the splenium of the corpus callosum, basal ganglia
      and internal capsule in a suspected case with tuberculous meningitis.
AB  - A 34-year-old man visited the hospital with chief complaints of headache, fever,
      and disturbance of consciousness. In view of his clinical condition, the course
      of the disease, and results of examination, he was diagnosed with viral
      meningitis and treated accordingly. However, his clinical condition worsened, and
      MRI revealed abnormal signals in the splenium of the corpus callosum, in the
      basal ganglia and in the internal capsule, as well as the presence of severe
      inflammation in the base of the brain. Since he had a high ADA level in the
      cerebrospinal fluid and was consequently suspected to have tuberculous
      meningitis, he was placed on antitubercular agents. Then, his clinical condition
      began to improve. Additional steroid pulse therapy further improved his
      condition, and abnormal signals in the splenium of the corpus callosum and the
      basal ganglia resolved. This valuable case suggests that an immune mechanism
      contributed to the occurrence of central nervous system symptoms associated with
      tuberculous meningitis.

PMID- 17443045
TI  - Scapular winging as a symptom of cervical flexion myelopathy.
AB  - A 23-year-old man complained of weakness of the right arm that he first noted six
      years prior to his visit. Neurological examination revealed atrophy and weakness
      of the triceps and serratus anterior muscle on the right side, which resulted in
      scapular winging on that side. MRI with neck flexion revealed compression of the
      cervical cord enabling a diagnosis of flexion myelopathy. Proximal muscle
      weakness and atrophy in flexion myelopathies including Hirayama disease are
      extremely rare. Here, we report a case of unilateral, proximal upper limb atrophy
      with scapular winging, attributed to middle cervical flexion myelopathy.

PMID- 17443046
TI  - Slowly progressive distal muscular atrophy of the bilateral upper limbs
      (O'Sullivan-McLeod syndrome) partially alleviated by intravenous immunoglobulin
      therapy.
AB  - We report a case of O'Sullivan-McLeod syndrome in a 59-year-old man, who had
      experienced slowly progressive weakening of both hands since he was 20 years of
      age. Mild hyperIgEemia and eosinophilia were present. Nerve conduction studies
      revealed reduced F wave-evoked frequencies for the median and ulnar nerves.
      Intravenous immunoglobulin (IVIG) at a dose of 400 mg/kg/day was given for 5
      days. After IVIG, the muscle weakness of the distal upper extremities improved
      together with increased F wave-evoked frequencies. These effects lasted for a few
      months. These observations suggest that immune-mediated neural damage partially
      contributes to O'Sullivan-McLeod syndrome.

PMID- 17443047
TI  - Pulmonary cryptococcosis presenting as endobronchial lesions in a patient under
      corticosteroid treatment.
AB  - We report a case of pulmonary cryptococcosis in an immunocompromised patient who
      had focal endobronchial lesions. When we first examined her, she complained of a
      productive cough that had lasted for two months. Seventeen months prior to this
      examination, she had been diagnosed with Sjogren syndrome and Sweet syndrome.
      Since that diagnosis, her condition had been maintained with low-dose
      prednisolone. We performed a chest CT scan, which revealed a mass, 3 cm in
      diameter, in the upper lobe of her left lung. A bronchoscopic examination
      revealed 3 white, elevated lesions in the upper lobe bronchus of her left lung.
      After 40 days of treatment with fluconazole, the shadow of her lung mass
      decreased in size to that of a scarred lesion and her white, elevated bronchial
      lesions disappeared.

PMID- 17443048
TI  - Nail dystrophy associated with AL amyloidosis.

PMID- 17443049
TI  - Pulmonary manifestation in neurofibromatosis type 1.

PMID- 17443050
TI  - Psammoma bodies in malignant pleural mesothelioma.

PMID- 17443051
TI  - Replacement of the bone marrow with metastatic breast cancer.

PMID- 17443052
TI  - Brachial plexus neurolymphomatosis: a discrepancy between electrophysiological
      and radiological findings.

PMID- 17443053
TI  - Isolated trochlear nerve palsy in herpes zoster ophthalmicus.

PMID- 17443054
TI  - Spinal cord herniation which manifested stepwise deterioration.

PMID- 17443055
TI  - MR findings in Call-Fleming syndrome.

PMID- 17443056
TI  - T2*-weighted MR images of a patient with familial cerebral cavernous
      malformation.

PMID- 17443057
TI  - Antitumor Activity of the Methanol Extract of Hypericum hookerianum Stem Against
      Ehrlich Ascites Carcinoma in Swiss Albino Mice.
AB  - A large number of plants belonging to the Hypericum family are known to possess
      strong antitumor properties. The methanol extract of H. hookerianum Wight and
      Arnott stem (MEHH) exhibited potent in vitro cytotoxic activity against various
      cancerous cell lines. In the present study, the high performance liquid
      chromatography (HPLC) standardized MEHH was tested for in vivo antitumor
      properties against Ehrlich ascites carcinoma (EAC) tumor bearing mice at 100,
      200, and 400 mg/kg body weight doses given orally once daily for 14 days. The
      results indicate that administration of the extract not only increased the
      survival of animals with ascites tumor, decreased the body weight induced by the
      tumor burden, and reduced packed cell volume and viable tissue cell count, but
      also altered many hematological parameters changed during tumor progression,
      indicating the potent antitumor nature of the extract. Among the three doses
      tested, the 200 mg/kg body weight dose was found to be the most potent.

PMID- 17443058
TI  - Tumor induction by monoenergetic neutrons in B6C3F1 mice.
AB  - This study was undertaken to investigate induction of tumors by monoenergetic
      neutrons in B6C3F1 mice. Individual groups of 6 week-old animals of both sexes
      (about 30 mice/group) were exposed to 0.5 Gy of various monoenergetic neutrons
      (dose rate 0.5 cGy/min) and then observed for 13 months. The incidences of tumors
      (mainly liver neoplasms) in non-irradiated male and female controls were 11% and
      0%, respectively. In the irradiated animals, the incidences were 53%, 50%, 60%
      and 43% in males, and 75%, 81%, 71%, and 85% in females, after 0.18, 0.32, 0.6
      and 1.0 MeV neutron exposure, respectively. There were no significant differences
      in the tumor induction rate among the different energy groups.

PMID- 17443059
TI  - Which nurse do you want?

PMID- 17443060
TI  - Communicating competence.

PMID- 17443068
TI  - Needlestick: adding insult to injury. Interview by Sibyl Shalo.

PMID- 17443073
TI  - Helping patients with end-stage renal disease.

PMID- 17443076
TI  - Sleep disruption in older adults. Harmful and by no means inevitable, it should
      be assessed for and treated.
AB  - Insomnia is not a normal part of aging, but nighttime sleep in older adults is
      often disrupted, leading to excessive daytime sleepiness and other physical,
      psychological, and cognitive changes that affect overall health. Even so,
      clinicians often pay little attention to sleep in this population. The sleep of
      older adults tends to be less deep than that of younger people, and coexisting
      conditions and treatment effects can more easily disrupt sleep. This article
      reviews the current literature on sleep disruption in older adults and suggests
      ways that nurses can apply the information in intervening to improve sleep in
      their older patients.

PMID- 17443079
TI  - Field expediency: how army nurses in Vietnam "made do". An ability to improvise
      is a valuable nursing skill, on and off the battlefield.
AB  - In the early years of the Vietnam War, when resources were in short supply,
      nurses improvised in the field to provide care to the sick and wounded under
      extremely adverse conditions. This "field expediency" was the result of nursing
      knowledge as well as flexibility, creativity, audacity, and pragmatism. Nurses in
      other settings--for example, those practicing in remote areas, in developing
      nations, or during natural disasters--may also find themselves facing severe
      shortages or too few essential supplies or a lack of equipment. Familiarity with
      the methods associated with field expediency will help nurses adapt quickly--on
      the battlefield and off.

PMID- 17443081
TI  - Educational mobility of RNs in North Carolina: who will teach tomorrow's nurses?
      A report on the first study to longitudinally examine educational mobility among
      nurses.
AB  - OBJECTIVE: Affected by the current nursing shortage, schools of nursing cite a
      lack of qualified nursing faculty as a primary barrier to program expansion. We
      sought to identify patterns in how nurses' entry-level degrees and other
      individual characteristics correlated with the timing and achievement of
      subsequent advanced nursing education. METHODS: Using longitudinal analysis of
      data gathered as part of North Carolina's licensing renewal process, we studied
      the educational mobility of newly graduated RNs with a variety of entry degrees
      in this state. We followed one cohort of 3,384 new graduates who were licensed in
      1984 (2,850 remained active and in the study at the 10-year point, and 2,418
      remained active and in the study at the 20-year point) and another cohort of
      5,341 new graduates who were licensed in 1994 (4,211 remained active and in the
      study at 10 years). Demographic data for a third cohort of 5,400 new graduates
      who were licensed in 2004 were included and considered along with data gathered
      by the National League for Nursing for nursing education research, to assist us
      in making comparisons between North Carolina and other states. RESULTS: Only 26%
      of the 2,418 members of the 1983-84 cohort at 20 years and 17% of the 4,211
      members of the 1993-94 cohort at 10 years pursued higher degrees, and just 19%
      and 12% of the respective cohorts did so in nursing. More than 80% of all nurses
      in either cohort who attained a master's degree in nursing or a doctorate in any
      field began their nursing career with a bachelor's degree. Younger age at entry
      into nursing, male sex, and belonging to a racial or ethnic minority were
      associated with being more likely to pursue higher academic degrees. CONCLUSIONS:
      Based on our findings, we suggest that increasing the number of graduates with a
      bachelor of science in nursing degree, especially those who are men or members of
      a racial or ethnic minority, will have the most immediate effect on increasing
      the potential nursing faculty pool.

PMID- 17443089
TI  - Online education.

PMID- 17443091
TI  - Her cap is now a hard hat. Interview by David Belcher.

PMID- 17443093
TI  - Reflections: finding the words.

PMID- 17443094
TI  - The value of clinical wisdom in randomised studies, real-world registries and new
      hypotheses.

PMID- 17443095
TI  - Disease management program for the elderly with heart failure.

PMID- 17443096
TI  - Application of the main implantable cardioverter-defibrillator trials and the
      2006 Guidelines for Management of Patients with Ventricular Arrhythmias and the
      Prevention of Sudden Cardiac Death.

PMID- 17443097
TI  - Two-year outcome of a prospective, controlled study of a disease management
      programme for elderly patients with heart failure.
AB  - OBJECTIVE: Elderly heart failure patients are at high risk of events. Available
      studies and systematic reviews suggest that elderly patients benefit from disease
      management programmes (DMPs). However, important questions remain open, including
      the optimal follow-up intensity and duration and whether such interventions are
      cost-effective during long-term follow-up and in different healthcare systems.
      The aim of this study was to determine the long-term efficacy of a hybrid DMP in
      consecutive older outpatients. METHODS: Intervention consisted in combined
      hospital-based (cardiologists and nurse-coordinators from two heart failure
      clinics) and home-based (patient's general practitioner visits) care. The
      components of the DMP were the following: discharge planning, education, therapy
      optimisation, improved communication, early attention to signs and symptoms.
      Intensive follow-up was based on scheduled hospital visits (starting within 14
      days of discharge), nurse's phone call and home general practitioner visits.
      RESULTS: A group of 173 patients aged > or =70 years (mean age 77 +/- 6 years,
      48% women) was randomly assigned to DMP (n = 86) or usual care (n = 87). At 2
      year follow-up, a 36% reduction in all-cause death and heart failure hospital
      admissions was observed in DMP vs. usual care. All-cause and heart failure
      admissions as well as the length of hospital stay were also reduced. DMP patients
      reported, compared to baseline, significant improvements in functional status,
      quality of life and beta-blocker prescription rate. The intervention was cost
      effective with a mean saving of euro 982.04 per patient enrolled. CONCLUSIONS: A
      hybrid DMP for elderly heart failure patients improves outcomes and is cost
      effective over a long-term follow-up.

PMID- 17443098
TI  - Left ventricle myocardial mechanics and textural properties in patients with
      Williams syndrome.
AB  - OBJECTIVE: To study left ventricular mechanics and textural properties in
      patients with Williams syndrome to define the impact of left ventricular
      hypertrophy on the functional findings. METHODS: Echocardiography was performed
      in 16 Williams syndrome patients (aged 1-25 years, mean 10 +/- 6 years), four
      with associated supravalvular aortic stenosis and seven with systemic
      hypertension. Fifteen age- and body surface area-matched subjects were selected
      as control group. Particularly, left ventricular geometry, myocardial
      contractility [midwall rate-corrected circumferential fiber shortening/end
      systolic meridional wall stress relationship (sigmaes)] and left ventricular
      diastolic function (mitral flow pattern and isovolumic relaxation time) were
      defined. In addition, integrated backscatter (IB) analysis intensity (IntIB) and
      cyclic variation (CVIB) were assessed for an ultrasonic myocardial
      characterization. RESULTS: Left ventricular hypertrophy was demonstrated in nine
      patients (56%) and abnormal left ventricular remodeling in ten patients (62%).
      Particularly seven of seven hypertensive patients and three of four patients with
      supravalvular aortic stenosis had abnormal remodeling; left ventricular geometry
      was normal in patients without hypertension or supravalvular aortic stenosis. In
      addition, midwall rate-corrected circumferential fiber shortening/(sigmaes)
      relationship was within the normal range in all patients. At integrated
      backscatter analysis, Williams syndrome patients showed, both at interventricular
      septum and posterior wall, reduced CVIB (9.36 +/- 2.16 versus 10.3 +/- 1.3 and
      8.65 +/- 2 versus 10.5 +/- 1.1). Compared to Williams syndrome patients without
      left ventricular hypertrophy (7/16), those with left ventricular hypertrophy
      (9/16) showed decreased mitral E/A ratio (1.32 +/- 0.09 versus 1.62 +/- 0.02),
      increased isovolumic relaxation time (68 +/- 7 versus 53 +/- 7) and increased
      IntIBS at interventricular septum (-27.3 +/- 0.07 versus -34 +/- 5). CONCLUSIONS:
      Our data obtained in young Williams syndrome patients show that: (i) mild left
      ventricular functional and textural abnormalities may be detected also in absence
      of significant supravalvular aortic stenosis and/or hypertension; (ii)
      significant left ventricular hypertrophy may develop since childhood; (iii)
      differences in left ventricular remodeling and/or degree of left ventricular
      hypertrophy may occur. Further studies are required to define the real impact of
      the functional abnormalities on the natural history in patients with Williams
      syndrome.

PMID- 17443099
TI  - Analysis of agreement between Duplex ultrasound scanning and arteriography in
      patients with lower limb artery disease.
AB  - BACKGROUND: Angiography is the gold standard for therapeutic decision-making in
      lower limb artery disease. However, both the potentiality and safety of Duplex
      ultrasound scanning suggest that it may become the main diagnostic tool. The
      present study aimed to investigate the agreement between Duplex scanning and
      angiography in the diagnosis of stenosis in lower limb artery disease. METHODS:
      Forty-nine patients with lower limb artery disease (24 claudication, 12 critical
      ischemia, 13 skin lesions) underwent angiography and Duplex scanning. The lower
      limb arterial axis was divided into 15 segments and graded on the basis of the
      degree of stenosis (0-49%, 50-69%, 70-99% and occlusion). Agreement between
      angiography and Duplex scanning was assessed by Cohen's kappa statistics (kappa).
      The sensitivity and specificity of Duplex scanning in detecting significant
      stenosis at angiography (>/= 70%) were also calculated. RESULTS: Good diagnostic
      agreement (kappa = 0.70; 95% CI 0.588-0.825) was achieved in the whole arterial
      axis. Agreement was good for the aorto-iliac district (kappa = 0.63) with a
      sensitivity of 63% and a specificity of 96%, and for the femoro-popliteal
      district (kappa = 0.70) with a sensitivity of 74% and a specificity of 83%. In
      infrapopliteal arteries, kappa showed a poor agreement, but Duplex scanning
      detected 28 patent tibial arteries in limbs that were not opacified on
      arteriography. CONCLUSIONS: Duplex scanning shows good agreement with angiography
      in lower limb artery disease on the whole, but poor agreement in infrapopliteal
      districts, with a low sensitivity and high specificity in detecting significant
      stenoses or occlusions.

PMID- 17443100
TI  - Carotid intima-media thickness, carotid distensibility and mitral, aortic valve
      calcification: a useful diagnostic parameter of systemic atherosclerotic disease.
AB  - BACKGROUND: Mitral (MAC) and aortic (AVC) calcification are observed more
      frequently in the elderly and are associated with coronary artery disease, aortic
      atheroma and peripheral arterial atherosclerotic disease. Common carotid intima
      media thickness (cIMT) and distensibility (cDIST) are also independent predictors
      of adverse cardiovascular outcomes. We examined the relationship between the
      degree of MAC-AVC and cIMT and cDIST. METHODS AND RESULTS: One hundred and forty
      three patients referred for transthoracic echocardiography and carotid artery
      echo-Doppler were evaluated; the variables measured were: systemic blood
      pressure, pulse pressure; body mass index, traditional risk factors, cIMT, cDIST
      (cDIST = [(csD - cdD)/PP]/csD; where csD and cdD were systolic and diastolic
      carotid diameters, respectively). MAC and AVC score, based on acoustic
      densitometry, were: 1 = absence of annular/valvular (av) sclerosis/calcification;
      2 = av sclerosis; 3 = av calcification; 4 = av calcification; 5 = av
      calcification with no recognition of the leaflets; the resulting score was the
      highest for either valvular annulus. Mean cIMT increased linearly with increasing
      valvular calcification score (P < 0.0001) whereas cDIST decreased for scores 1 to
      5 (P < 0.0001). Distribution of cIMT quartiles showed that 75% of the patients in
      the lowest quartile had a score of 1 and 70% of patients in the highest quartile
      had a score of 5; 47% of the patients in the highest quartile of cDIST had a
      score of 1, whereas 60% of patients in the lowest quartile of cDIST had a score
      of 4. CONCLUSIONS: The MAC and AVC score identifies subgroups of patients with
      different cIMT and cDIST. These data may confirm MAC-AVC as a useful important
      diagnostic parameter of systemic atherosclerotic disease.

PMID- 17443101
TI  - Effectiveness of video-based patient information before percutaneous cardiac
      interventions.
AB  - BACKGROUND: Coronary angiography and angioplasty entail both major and minor
      risks for patients. Patient information is therefore especially important because
      risks can be reduced if some basic preventive measures are adopted (e.g. allergic
      reactions), and potentially dangerous behaviours are avoided afterwards. A video
      based presentation was conducted to improve patient information in our centre.
      The effectiveness of this new instrument, in addition to the standard information
      sheet, was assessed. METHODS: The video-based presentation was proposed to a
      sample of 108 consecutive patients, who had read the standard information sheet,
      before elective coronary angiography. Before and after watching the video, the
      patients were asked the same eight multiple-choice questions covering some
      important technical aspects of the interventions and precautions that were to be
      taken. All data were present in both the information sheet and the video.
      RESULTS: Out of 108 patients, 100 agreed to watch the video and answer the
      questions. Overall, the percentage of correct answers increased from 39% to 77%
      (P < 0.0001) after watching the video, with a reduction in 'don't know' answers
      from 53% to 10% (P < 0.0001), and a non-significant increase in wrong answers
      from 8% to 13% (P = 0.183). CONCLUSIONS: The video was shown to improve the
      knowledge of our patients about percutaneous coronary interventions, and was
      welcomed, especially because it made patients more familiar with both the
      environment of the cathlab and the technical aspects of the procedures.

PMID- 17443102
TI  - Edge-to-edge mitral valve repair for isolated prolapse of the anterior leaflet
      caused by degenerative disease.
AB  - OBJECTIVE: The use of new techniques to correct mitral regurgitation due to
      prolapse of the anterior leaflet has been shown to expand the original surgical
      armamentarium and to improve postoperative outcome. We retrospectively analysed
      our experience with isolated prolapse of the anterior mitral leaflet repaired
      using the edge-to-edge technique. METHODS: From October 1986 to June 2004, 790
      patients underwent mitral valve repair for mitral regurgitation at our
      institution. Isolated pathology of the anterior mitral leaflet, due to
      degenerative disease, was the cause of mitral regurgitation in 84 patients and,
      from 1991, 68 underwent edge-to-edge repair. RESULTS: There was no intraoperative
      death and one in-hospital death. Three patients died in the late follow-up period
      for a cumulative 13-year survival rate of 90 +/- 1.4%. No patient underwent early
      reoperation. Four patients underwent reoperation during the follow-up for a
      cumulative 13-year freedom from reoperation of 92.3 +/- 3.2%. At
      echocardiographic evaluation, mitral valve repair failure was associated with
      severe mitral regurgitation in four patients. Of the remaining 60 patients, 40
      had no residual regurgitation, 18 had trivial residual regurgitation, and two had
      mild regurgitation. At follow-up, 49 patients are still in New York Heart
      Association (NYHA) class I, 14 in NYHA class II and only one in NYHA class III.
      CONCLUSIONS: Our study demonstrates that the 'edge-to-edge' technique is a
      reliable procedure to correct prolapsing leaflets. The addition of this technique
      to the surgical armamentarium has neutralized prolapse of the anterior leaflet as
      an incremental risk factor for reoperation.

PMID- 17443103
TI  - Drug-eluting stents or drug-eluting conduits for multivessel disease?

PMID- 17443104
TI  - Stenting the coronaries and bypassing the evidence in patients with multivessel
      coronary artery disease: time to set the record straight.

PMID- 17443105
TI  - Out of the guidelines: should an intracardiac defibrillator be implanted in
      patients with recurrent early ventricular fibrillation due to recurrent acute
      myocardial infarction?
AB  - We report the case of a patient admitted to the hospital on two different
      occasions, separated by a time interval of 12 years, with the same clinical
      picture: acute anterior myocardial infarction complicated by early ventricular
      fibrillation. The patient was successfully resuscitated because, in both
      circumstances, he was 'lucky' to arrive at hospital within a few minutes of the
      onset of chest pain, and to have ventricular fibrillation in the Emergency
      Department. The issue of intracardiac defibrillator implantation, despite this
      situation is not contemplated in the current guidelines (left ventricular
      ejection fraction was preserved), is discussed here.

PMID- 17443106
TI  - A serious complication of thrombolysis after prolonged cardiac arrest: airway
      obstruction from tongue injury.
AB  - Prolonged cardiac arrest with external chest compression was regarded as a
      contraindication to thrombolysis for acute myocardial infarction, although recent
      work has largely refuted previous concerns. This paper presents a serious
      haemorrhagic complication, which risked airway patency due to unrecognised
      nasopharyngeal airway-induced trauma and tongue biting. The patient required
      blood transfusion, and owing to the haemorrhage was unable to have rescue
      angioplasty. Methods of revascularisation after prolonged cardiac arrest are
      discussed.

PMID- 17443107
TI  - In-stent restenosis and multislice computed tomography: is the method ready to
      start?
AB  - We present two patients revascularized by coronary stents and evaluated by
      multislice computed tomography (CT). In first patient, angio-CT (16
      slices/rotation scanner) detected a high-grade restenosis on the distal part of a
      drug-eluting stent; conventional coronary angiography confirmed the diagnosis. In
      second patient, angio-CT (64 slices/rotation) showed a tissue proliferation, non
      flow-limiting, in the proximal part of a bare metal stent; conventional
      angiography confirmed the diagnosis. Blooming effects and partial volume
      averaging still limit the widespread application of this method. New scanners and
      the use of a special convolution kernel are likely to improve the accuracy of CT
      angiography in patients with stents.

PMID- 17443109
TI  - Aortic arch stabilization in redo operations for aortic type A dissection.
AB  - BACKGROUND: In patients undergoing a new surgical procedure after correction of
      type A dissection, care must be taken to correct as much as possible the residual
      lesions and to obliterate, if possible, any residual false lumen. METHODS: From
      November 2003 to May 2004, four patients who previously underwent ascending
      aortic replacement for acute type A aortic dissection underwent a second
      procedure because of severe aortic root dilatation. The residual false lumen was
      limited to the arch in two cases, but extended to the whole thoracic aorta in the
      other two, going down to the abdominal aorta in one of them. A composite valve
      conduit was inserted, and then a stent was placed in the dissected aortic arch.
      RESULTS: All patients had a regular postoperative outcome and were discharged 9
      11 days after surgery. The computed tomography angiography scan, performed early
      and after 6 months, showed no evidence of false lumen in the aortic arch.
      CONCLUSIONS: The placement of a stent in the aortic arch in redo cases can be
      performed with satisfying results because it causes the disappearance of the
      false lumen. Long-term follow-up is required for the confirmation of these
      initial positive results.

PMID- 17443108
TI  - Long drug-eluting stent implantation for a diffusely diseased right internal
      mammary artery.
AB  - The frequent use of the internal mammary artery as a bypass graft has brought
      about an increasing need for angioplasty to treat stenotic arterial grafts.
      Percutaneous interventions of internal mammary artery grafts by balloon
      angioplasty or stenting with bare-metal stents have been described in the past.
      However, implantation of bare-metal stents was associated with high rates of
      restenosis. The introduction of drug-eluting stents for the treatment of diseased
      native coronary vessels has been associated with a reduced need for repeat
      intervention compared with bare-metal stents for both low-risk lesions and high
      risk, complex lesions, including the 'long lesion' subset. We describe a case of
      long drug-eluting stent implantation for a diffusely diseased right internal
      mammary artery.

PMID- 17443110
TI  - The complex link between oxidised low-density lipoprotein and unstable angina.
AB  - OBJECTIVE: The role of oxidised low-density lipoprotein (ox-LDL) in plaque
      destabilisation is controversial; therefore we aimed at comparing plaque and
      plasma ox-LDL content in stable and unstable ischaemic syndromes. We also
      assessed the correlation between plaque or plasma ox-LDL and angiographic complex
      stenosis morphology. METHODS: Ten consecutive patients with chronic stable angina
      (SA) and 10 consecutive patients with unstable angina (UA) were studied. Plaque
      sections obtained by directional coronary atherectomy were immunostained with the
      monoclonal antibody mAb-4E6, which recognises several oxidation epitopes on LDL
      (mAb-4E6 ox-LDL), and with the monoclonal antibody mAb-1H11 (mAb-1H11 ox-LDL),
      which recognises malondialdehyde-modified LDL. An mAb-4E6-based competition ELISA
      was used for quantification of ox-LDL in plasma. C-reactive protein serum levels
      were measured by a high-sensitivity nephelometric assay. An angiographic analysis
      was performed to assess severity and extent of coronary atherosclerotic disease
      and stenosis morphology. RESULTS: Percent plaque area occupied by mAb-4E6 ox-LDL
      or mAb-1H11 ox-LDL was similar in patients with SA or UA (22.4 +/- 13.1 vs. 21.1
      +/- 19.7%, P = 0.8 and 19.3 +/- 10.4 vs. 16.8 +/- 16.9%, P = 0.6, respectively),
      whereas ox-LDL plasma levels were significantly higher in patients with UA than
      in patients with SA (2.4 +/- 1.1 vs. 0.9 +/- 0.6 mg/dl; P = 0.03). Furthermore, a
      significant correlation was found between plasma levels of ox-LDL and the number
      of angiographically complex lesions (P = 0.03) or C-reactive protein serum levels
      (P = 0.04). CONCLUSIONS: Neither plaque mAb-4E6 ox-LDL nor plaque mAb-1H11 ox-LDL
      seem to be a major trigger of coronary plaque instability. However, circulating
      ox-LDL might be involved in plaque vulnerability and coronary artery disease
      activity.

PMID- 17443111
TI  - A wandering pacemaker lead.

PMID- 17443112
TI  - Magnetic resonance imaging of a bioprosthetic mitral valve: a smiling heart.

PMID- 17443114
TI  - Evaluation of item candidates: the PROMIS qualitative item review.
AB  - One of the PROMIS (Patient-Reported Outcome Measurement Information System)
      network's primary goals is the development of a comprehensive item bank for
      patient-reported outcomes of chronic diseases. For its first set of item banks,
      PROMIS chose to focus on pain, fatigue, emotional distress, physical function,
      and social function. An essential step for the development of an item pool is the
      identification, evaluation, and revision of extant questionnaire items for the
      core item pool. In this work, we also describe the systematic process wherein
      items are classified for subsequent statistical processing by the PROMIS
      investigators. Six phases of item development are documented: identification of
      extant items, item classification and selection, item review and revision, focus
      group input on domain coverage, cognitive interviews with individual items, and
      final revision before field testing. Identification of items refers to the
      systematic search for existing items in currently available scales. Expert item
      review and revision was conducted by trained professionals who reviewed the
      wording of each item and revised as appropriate for conventions adopted by the
      PROMIS network. Focus groups were used to confirm domain definitions and to
      identify new areas of item development for future PROMIS item banks. Cognitive
      interviews were used to examine individual items. Items successfully screened
      through this process were sent to field testing and will be subjected to
      innovative scale construction procedures.

PMID- 17443115
TI  - Psychometric evaluation and calibration of health-related quality of life item
      banks: plans for the Patient-Reported Outcomes Measurement Information System
      (PROMIS).
AB  - BACKGROUND: The construction and evaluation of item banks to measure
      unidimensional constructs of health-related quality of life (HRQOL) is a
      fundamental objective of the Patient-Reported Outcomes Measurement Information
      System (PROMIS) project. OBJECTIVES: Item banks will be used as the foundation
      for developing short-form instruments and enabling computerized adaptive testing.
      The PROMIS Steering Committee selected 5 HRQOL domains for initial focus:
      physical functioning, fatigue, pain, emotional distress, and social role
      participation. This report provides an overview of the methods used in the PROMIS
      item analyses and proposed calibration of item banks. ANALYSES: Analyses include
      evaluation of data quality (eg, logic and range checking, spread of response
      distribution within an item), descriptive statistics (eg, frequencies, means),
      item response theory model assumptions (unidimensionality, local independence,
      monotonicity), model fit, differential item functioning, and item calibration for
      banking. RECOMMENDATIONS: Summarized are key analytic issues; recommendations are
      provided for future evaluations of item banks in HRQOL assessment.

PMID- 17443116
TI  - The Patient-Reported Outcomes Measurement Information System (PROMIS): progress
      of an NIH Roadmap cooperative group during its first two years.
AB  - BACKGROUND: The National Institutes of Health (NIH) Patient-Reported Outcomes
      Measurement Information System (PROMIS) Roadmap initiative (www.nihpromis.org) is
      a 5-year cooperative group program of research designed to develop, validate, and
      standardize item banks to measure patient-reported outcomes (PROs) relevant
      across common medical conditions. In this article, we will summarize the
      organization and scientific activity of the PROMIS network during its first 2
      years. DESIGN: The network consists of 6 primary research sites (PRSs), a
      statistical coordinating center (SCC), and NIH research scientists. Governed by a
      steering committee, the network is organized into functional subcommittees and
      working groups. In the first year, we created an item library and activated 3
      interacting protocols: Domain Mapping, Archival Data Analysis, and Qualitative
      Item Review (QIR). In the second year, we developed and initiated testing of item
      banks covering 5 broad domains of self-reported health. RESULTS: The domain
      mapping process is built on the World Health Organization (WHO) framework of
      physical, mental, and social health. From this framework, pain, fatigue,
      emotional distress, physical functioning, social role participation, and global
      health perceptions were selected for the first wave of testing. Item response
      theory (IRT)-based analysis of 11 large datasets supplemented and informed item
      level qualitative review of nearly 7000 items from available PRO measures in the
      item library. Items were selected for rewriting or creation with further detailed
      review before the first round of testing in the general population and target
      patient populations. CONCLUSIONS: The NIH PROMIS network derived a consensus
      based framework for self-reported health, systematically reviewed available
      instruments and datasets that address the initial PROMIS domains. Qualitative
      item research led to the first wave of network testing which began in the second
      year.

PMID- 17443117
TI  - Item response theory analyses of physical functioning items in the medical
      outcomes study.
AB  - BACKGROUND: Constructing and evaluating item pools that measure a single domain
      of health-related quality of life (HRQOL) is one of the fundamental objectives of
      the Patient Reported Outcome Measurement and Information System (PROMIS) project.
      The initial focus of PROMIS is on 5 HRQOL domains: physical function, fatigue,
      pain, emotional distress, and social/role participation. Analysis of related,
      available data can inform construction of these new banks. OBJECTIVE: We sought
      to inform the building of the PROMIS physical function item bank by evaluating
      physical functioning items administered to participants in the Medical Outcomes
      Study. RESEARCH DESIGN: Secondary analyses of physical functioning items
      administered at baseline (Fall, 1986) to 3223 individuals in the Medical Outcomes
      Study. SUBJECTS: The mean age of participants was 54 years old; 15% had less than
      a high school education, 30% had a high school education, 27% had some but <4
      years of college, and 28% had 4 or more years of college. Sixty-one percent were
      female; 80% were non-Hispanic white, 14% non-Hispanic black, 3% Hispanic, 1%
      Asian, and 2% other race/ethnicity. MEASURES: Fifteen physical functioning items
      were selected for analyses including the 10 SF-36 physical functioning items, an
      item assessing limitations in everyday physical activities because of health
      problems, an item measuring satisfaction with physical ability, and 3 mobility
      items. RESULTS: Cronbach's alpha was 0.94 for the 15-item scale and item-total
      correlations ranged from 0.51 (limited in bathing or dressing) to 0.80 (limited
      walking several blocks). A one-factor confirmatory categorical model fit the data
      well according to practical fit indices (comparative fit index = 0.95), but the
      Root Mean Square Error of Approximation was 0.12. Estimated factor loadings were
      all large (0.72 to 0.96) and statistically significant. We fit the graded
      response model with freely estimated and fixed slope estimates to compare 2-PL
      and 1-PL models. The difference between these 2 goodness of fit statistics for
      the 2 models was statistically significant: chi (df = 14) = 772.9, P < 0.001.
      Slope estimates for some of the items in the 2-PL model varied from the 1-PL
      common slope to a noteworthy extent (eg, items 2, 5, 7, 8, and 9). Category
      threshold estimates generally were similar for the 2 models. Threshold estimates
      for the 2-PL model ranged from -2.90 (item 14: between no, never, and yes,
      occasionally in bed or in a chair most or all of the day because of health) to
      1.55 (item 12: between very satisfied and completely satisfied with physical
      ability to do what you want to do). Information peaked at -1.0 theta (information
      = 33.60) for the 2-PL model. Information was only 7.43 at 0.8 theta (2-PL) and
      decreased with increasing theta. CONCLUSIONS: The 15 physical functioning items
      provide reasonably good fit to a unidimensional item response theory model that
      provides satisfactory coverage of the lower levels of physical functioning but
      does not provide very much information at higher levels of functioning.

PMID- 17443118
TI  - Practical issues in the application of item response theory: a demonstration
      using items from the pediatric quality of life inventory (PedsQL) 4.0 generic
      core scales.
AB  - BACKGROUND: Item response theory (IRT) is increasingly being applied to health
      related quality of life instrument development and refinement. This article
      discusses results obtained using categorical confirmatory factor analysis (CCFA)
      to check IRT model assumptions and the application of IRT in item analysis and
      scale evaluation. OBJECTIVES: To demonstrate the value of CCFA and IRT in
      examining a health-related quality of life measure in children and adolescents.
      METHODS: This illustration uses data from 10,241 children and their parents on
      items from the 4 subscales of the PedsQL 4.0 Generic Core Scales. CCFA was
      applied to confirm domain dimensionality and identify possible locally dependent
      items. IRT was used to assess the strength of the relationship between the items
      and the constructs of interest and the information available across the latent
      construct. RESULTS: CCFA showed generally strong support for 1-factor models for
      each domain; however, several items exhibited evidence of local dependence. IRT
      revealed that the items generally exhibit favorable characteristics and are
      related to the same construct within a given domain. We discuss the lessons that
      can be learned by comparing alternate forms of the same scale, and we assess the
      potential impact of local dependence on the item parameter estimates.
      CONCLUSIONS: This article describes CCFA methods for checking IRT model
      assumptions and provides suggestions for using these methods in practice. It
      offers insight into ways information gained through IRT can be applied to
      evaluate items and aid in scale construction.

PMID- 17443119
TI  - Considerations for developing interfaces for collecting patient-reported outcomes
      that allow the inclusion of individuals with disabilities.
AB  - PROMIS (Patient-Reported Outcome Measurement Information System) is developing a
      set of tools for collecting patient reported outcomes, including computerized
      adaptive testing that can be administered using different modes, such as
      computers or phones. The user interfaces for these tools will be designed using
      the principles of universal design to ensure that it is accessible to all users,
      including those with disabilities. We review the rationale for making health
      assessment instruments accessible to users with disabilities, briefly review the
      standards and guidelines that exist to support developers in the creation of user
      interfaces with accessibility in mind, and describe the usability and
      accessibility testing PROMIS will conduct with content experts and users with and
      without disabilities. Finally, we discuss threats to validity and reliability
      presented by universal design principles. We argue that the social and practical
      benefits of interfaces designed to include a broad range of potential users,
      including those with disabilities, seem to outweigh the need for standardization.
      Suggestions for future research are also included.

PMID- 17443120
TI  - Human rabies--Indiana and California, 2006.
AB  - Rabies is a viral infection that causes acute, progressive encephalitis and is
      considered to be universally fatal. However, during 2004, an unvaccinated
      Wisconsin patient received a new medical treatment and became the first
      documented survivor of rabies who had not received preexposure vaccination or
      postexposure prophylaxis (PEP), suggesting the possibility of successful future
      interventions. This report describes two recent patients with rabies who were
      treated using therapy similar to that used for the Wisconsin patient; both
      treatments were unsuccessful. The report also describes the concomitant
      epidemiologic investigations by the Indiana State Department of Health (ISDH),
      California Department of Health Services (CDHS), and CDC, and the local public
      health responses in Marshall County, Indiana, and San Joaquin and Alameda
      counties in California. The findings in this report underscore the continuing
      need for enhanced clinical awareness of possible rabies exposure to ensure prompt
      PEP and timely diagnosis of rabies, especially if treatment is attempted.

PMID- 17443121
TI  - Use of niacin in attempts to defeat urine drug testing--five states, January
      September 2006.
AB  - In addition to its use as a nutritional supplement, niacin (nicotinic acid or
      vitamin B3) is medically prescribed to treat hyperlipidemia and
      hypercholesterolemia. Use of niacin in low doses usually leads to few adverse
      drug reactions (ADRs); however, at larger doses, niacin can cause skin flushing,
      itching, and occasionally more serious effects. The 2005 annual report of the
      American Association of Poison Control Centers documented 3,109 reports of
      exposures to niacin. During 2006, the Rocky Mountain Poison and Drug Center
      (RMPDC) in Denver, Colorado, received multiple calls regarding ADRs after
      nonmedical use of niacin. A review of call records indicated various uses of
      niacin, including attempts to alter or mask results of urine drug tests, although
      no scientific evidence exists that ingestion of niacin can alter a drug test
      result. To determine the extent of niacin use in attempts to alter drug test
      results, reports to RMPDC of niacin ADRs were reviewed for the period January-
      September 2006. The results identified 18 persons who reported nonsuicidal,
      intentional, nonmedical reasons for using niacin, including eight who specified
      altering drug test results as their reason for using niacin. Ten other persons,
      among an additional 18 who offered no reason for niacin use, were categorized as
      possible users of niacin to try to alter drug test results because of their ages
      or the amount of niacin ingested. Clinicians, especially those whose patients
      include teens and young adults, should be aware of the potential use of niacin in
      attempts to defeat urine drug tests.

PMID- 17443122
TI  - Hypothermia-related mortality--Montana, 1999-2004.
AB  - Hypothermia, defined as a core body temperature of <95 degrees F (35 degrees C),
      occurs in persons exposed to excessive cold. Although hypothermia can be fatal,
      it also is preventable. Risk factors for death from hypothermia include advanced
      age, substance abuse, altered mental status, and increased contact with
      substances that promote heat loss, such as water. Montana has an intensely cold
      and long winter. In December, the average daily minimum temperature is
      approximately 18.0 degrees F (-7.7 degrees C) and can remain at that level until
      March. For the entire year in Montana, the average daily minimum temperature is
      35.9 degrees F (2.2 degrees C). During the period 1999-2004, Montana had the
      second highest (after Alaska) average annual hypothermia-related mortality rate
      (1.08 deaths per 100,000 population) in the United States, approximately five
      times greater than the U.S. rate overall. This report describes three examples of
      case reports of hypothermia-related deaths in Montana during 2005-2006,
      summarizes hypothermia-related mortality in the state during 1999-2004 (the most
      recent period for which annual data were available), and discusses hypothermia
      risk factors and prevention measures. Enhanced education and intervention
      strategies, particularly targeted to older adults, might reduce the number of
      deaths from hypothermia in Montana.

PMID- 17443123
TI  - Brief report: Gastroenteritis among attendees at a summer cAMP--Wyoming, June
      July 2006.
AB  - On July 19, 2006, the Environmental Protection Agency (EPA) notified the Wyoming
      Department of Health (WDH) of an Escherichia coli-positive well-water sample,
      indicating fecal contamination, that had been submitted from a Wyoming summer
      youth camp after the camp manager noticed cases of gastroenteritis among campers
      and staff members. This report describes the subsequent investigation by WDH, the
      Wyoming Department of Agriculture (WDA), and the Wyoming Department of
      Environmental Quality (WDEQ), which identified Norovirus and Campylobacter
      species as the etiologic agents.

PMID- 17443124
TI  - Opioid-dependent anticipatory negative contrast and binge-like eating in rats
      with limited access to highly preferred food.
AB  - Binge eating and an increased role for palatability in determining food intake
      are abnormal adaptations in feeding behavior linked to eating disorders and body
      weight dysregulation. The present study tested the hypothesis that rats with
      limited access to highly preferred food would develop analogous opioid-dependent
      learned adaptations in feeding behavior, with associated changes in metabolism
      and anxiety-like behavior. For this purpose, adolescent female Wistar rats were
      daily food deprived (2 h) and then offered 10-min access to a feeder containing
      chow followed sequentially by 10-min access to a different feeder containing
      either chow (chow/chow; n=7) or a highly preferred, but macronutrient-comparable,
      sucrose-rich diet (chow/preferred; n=8). Chow/preferred-fed rats developed binge
      like hyperphagia of preferred diet from the second feeder and anticipatory chow
      hypophagia from the first feeder with a time course suggesting associative
      learning. The feeding adaptations were dissociable in onset, across individuals,
      and in their dose-response to the opioid-receptor antagonist nalmefene,
      suggesting that they represent distinct palatability-motivated processes.
      Chow/preferred-fed rats showed increased anxiety-like behavior in relation to
      their propensity to binge as well as increased feed efficiency, body weight, and
      visceral adiposity. Chow/preferred-fed rats also had increased circulating leptin
      levels and decreased growth hormone and 'active' ghrelin levels. Thus, the short
      term control of food intake in rats with restricted access to highly preferred
      foods comes to rely more on hedonic, rather than nutritional, properties of food,
      through associative learning mechanisms. Such rats show changes in ingestive,
      metabolic, endocrine, and anxiety-related measures, which resemble features of
      binge eating disorders or obesity.

PMID- 17443125
TI  - Dose-related enhancement of mood and cognition in smokers administered nicotine
      nasal spray.
AB  - The discovery of the role of nicotinic receptors in attention and memory has led
      to the testing of nicotinic analogs as cognitive enhancing agents in patient
      populations. Empirical information about nicotine's ability to enhance elements
      of attention and memory in normal individuals might guide development of
      therapeutic uses of nicotine in cognitively impaired populations. The purpose of
      this study was to determine the effect of nicotine on continuous attention,
      working memory, and computational processing in tobacco-deprived and nondeprived
      smokers. A total of 28 smokers (14 men, 14 women) participated in a double-blind,
      placebo-controlled, within-subject study, in which they were overnight (12 h)
      tobacco deprived at one session and smoked ad libitum before the other session.
      At each session, participants received 0, 1, and 2 mg nicotine via nasal spray in
      random order at 90 min intervals. Before and after each dose, a battery of
      cognitive, subjective, and physiological measures was administered, and blood
      samples were taken for plasma nicotine concentration. Overnight tobacco
      deprivation resulted in impaired functioning on all cognitive tests and increased
      self-reports of tobacco craving and negative mood; nicotine normalized these
      deficits. In the nondeprived condition, nicotine enhanced performance on the
      continuous performance test (CPT) and an arithmetic test in a dose-related
      manner, but had no effect on working memory. In general, women were more
      sensitive than men to the subjective effects of nicotine. These results provide
      an unequivocal determination that nicotine enhanced attentional and computational
      abilities in nondeprived smokers and suggest these cognitive domains as
      substrates for novel therapeutic indications.

PMID- 17443126
TI  - The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia
      and nonpsychiatric controls.
AB  - Abundant evidence indicates that the neuronal nicotinic acetylcholine receptor
      (nAChR) system is integral to regulation of attentional processes and is
      dysregulated in schizophrenia. Nicotinic agonists may have potential for the
      treatment of cognitive impairment in this disease. This study investigated the
      effects of transdermal nicotine on attention in individuals with schizophrenia
      (n=28) and healthy controls (n=32). All participants were nonsmokers in order to
      eliminate confounding effects of nicotine withdrawal and reinstatement that may
      occur in the study of smokers. Subjects received 14 mg transdermal nicotine and
      identical placebo in a randomized, placebo-controlled, crossover design. A
      cognitive battery was conducted before and 3 h after each patch application. The
      primary outcome measure was performance on the Continuous Performance Test
      Identical Pairs (CPT-IP) Version. Nicotine significantly improved the performance
      on the CPT-IP as measured by hit reaction time, hit reaction time standard
      deviation and random errors in both groups. In addition, nicotine reduced
      commission errors on the CPT-IP and improved the performance on a Card Stroop
      task to a greater extent in those with schizophrenia vs controls. In summary,
      nicotine improved attentional performance in both groups and was associated with
      greater improvements in inhibition of impulsive responses in subjects with
      schizophrenia. These results confirm previous findings that a single dose of
      nicotine improves attention and suggest that nicotine may specifically improve
      response inhibition in nonsmokers with schizophrenia.

PMID- 17443128
TI  - Involvement of arginine vasopressin and V1b receptor in heroin withdrawal and
      heroin seeking precipitated by stress and by heroin.
AB  - A previous study has shown that the stress responsive neurohormone arginine
      vasopressin (AVP) is activated in the amygdala during early withdrawal from
      cocaine. The present studies were undertaken to determine whether (1) AVP mRNA
      levels in the amygdala or hypothalamus, as well as hypothalamic-pituitary-adrenal
      (HPA) activity, would be altered during chronic intermittent escalating heroin
      administration (10 days; 7.5-60 mg/kg/day) or during early (12 h) and late (10
      days) spontaneous withdrawal; (2) foot shock stress would alter AVP mRNA levels
      in the amygdala or hypothalamus in rats withdrawn from heroin self-administration
      (7 days, 3 h/day, 0.05 mg/kg/infusion); and (3) the selective V1b receptor
      antagonist SSR149415 (1 and 30 mg/kg, intraperitoneal) would alter heroin seeking
      during tests of reinstatement induced by foot shock stress and by heroin primes
      (0.25 mg/kg), as well as HPA hormonal responses to foot shock. We found that AVP
      mRNA levels were increased during early spontaneous withdrawal in the amygdala
      only. This amygdalar AVP mRNA increase was no longer observed at the later stage
      of heroin withdrawal. Foot shock stress increased AVP mRNA levels in the amygdala
      of rats withdrawn from heroin self-administration, but not in heroin naive rats.
      Behaviorally, SSR149415 dose-dependently attenuated foot shock-induced
      reinstatement and blocked heroin-induced reinstatement. Finally, SSR149415
      blunted the HPA activation by foot shock. Together, these data in rats suggest
      that stress responsive AVP/V1b receptor systems (including the amygdala) may be
      critical components of the neural circuitry underlying the aversive emotional
      consequences of drug withdrawal, as well as the effect of negative emotional
      states on drug-seeking behavior.

PMID- 17443127
TI  - Effects of cocaine and MDMA self-administration on serotonin transporter
      availability in monkeys.
AB  - Although serotonin (5-HT) can interact with dopamine (DA) systems to modulate the
      subjective and reinforcing effects of psychostimulants such as cocaine and 3,4
      methyldioxymethamphetamine (MDMA, ecstasy), the long-term effects of exposure to
      psychostimulants on brain 5-HT systems are not well characterized. The present
      study assessed 5-HT transporter (SERT) availability using positron emission
      tomography (PET) in rhesus monkeys with the SERT-specific radioligand [(11)C]3
      amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB). SERT
      availability was assessed in regions of interest including the caudate nucleus,
      putamen, anterior cingulate cortex, and cerebellum. [(11)C]DASB distribution
      volume ratios (DVRs) were calculated using the cerebellum as the reference
      region. DVRs were calculated in control monkeys and in cocaine or MDMA self
      administering monkeys approximately 24 h after the last self-administration (SA)
      session. SERT availability did not differ between monkeys with a history of MDMA
      SA and control monkeys in any region examined. In contrast, monkeys with a
      history of cocaine SA showed significantly higher levels of SERT availability in
      the caudate nucleus and putamen compared to control subjects. These results
      suggest that chronic SA of cocaine, but not MDMA, leads to alterations in
      serotonergic function in brain areas relevant to drug abuse. The higher level of
      SERT availability in cocaine-experienced monkeys may lead to a reduced inhibitory
      tone of 5-HT on the DA system, which may explain, in part, differences in the
      abuse liability between cocaine and MDMA.

PMID- 17443129
TI  - Antisense oligodeoxynucleotides for estrogen receptor-beta and alpha attenuate
      estradiol's modulation of affective and sexual behavior, respectively.
AB  - Estradiol (E(2)) modulates affective and socio-sexual behavior of female rodents.
      E(2)'s functional effects may involve actions through alpha and beta isoforms of
      estrogen receptor (ERs). The importance of E(2)'s actions at these isoforms for
      anxiety (open field, elevated plus maze), depression (forced swim test), and
      sexual behavior (lordosis) was investigated using an antisense oligonucleotide
      (AS-ODN) strategy. If ERbeta is required for anti-anxiety and antidepressant-like
      effects, and ERalpha is required for sexual receptivity, of E(2), then
      intracerebroventricular administration of AS-ODNs against these ERs should
      attenuate these effects and reduce immunoreactivity of ERs in brain regions that
      mediate these behaviors, such as the hippocampus and ventral medial hypothalamus
      (VMH). Ovariectomized rats were primed with 17beta-E(2) (10 microg) 48 h before
      testing (hour 0). At hours 0, 24, and 47.5, rats were infused with saline
      vehicle, scrambled control AS-ODNs, or AS-ODNs targeted against ERalpha and/or
      ERbeta, and were tested at hour 48. Rats infused with ERbeta AS-ODNs, alone, or
      with ERalpha AS-ODNs had significantly decreased open field central entries,
      decreased plus maze open arm time and entries, increased time spent immobile, and
      decreased time spent swimming in the forced swim test, and decreased ERbeta
      immunoreactivity in the brain than did rats administered ERalpha AS-ODNs,
      vehicle, or scrambled AS-ODNs. Rats that were administered ERalpha AS-ODNs,
      alone, or with ERbeta AS-ODNs had significantly decreased lordosis and decreased
      ERalpha immunoreactivity in the brain compared to rats administered ERbeta AS
      ODNs, vehicle, or scrambled AS-ODNs. Thus, ERbeta and ERalpha may be required for
      E(2)'s modulation of affective and sexual behavior, respectively.

PMID- 17443130
TI  - Relative prenatal and postnatal maternal contributions to schizophrenia-related
      neurochemical dysfunction after in utero immune challenge.
AB  - Prenatal exposure to infections represents a risk factor for the emergence of
      neuropsychiatric disorders in later life, including schizophrenia and autism.
      However, it remains essentially unknown whether this association is primarily
      attributable to prenatal and/or postnatal maternal effects on the offspring.
      Here, we addressed this issue by dissecting the relative contributions of
      prenatal inflammatory events and postnatal maternal factors in an animal model of
      prenatal viral-like infection. Pregnant mice were exposed to the inflammatory
      agent polyriboinosinic-polyribocytidilic acid (PolyI:C; 5 mg/kg, i.v.) or vehicle
      treatment on gestation day 9, and offspring born to PolyI:C- and vehicle-treated
      dams were cross fostered to surrogate rearing mothers that had either experienced
      inflammatory or sham treatment during pregnancy. We demonstrate that a variety of
      dopamine- and glutamate-related pharmacological and neuroanatomical disturbances
      emerge after prenatal immune challenge regardless of whether neonates were raised
      by vehicle- or PolyI:C-exposed surrogate mothers. However, the adoption of
      prenatal control animals to immune-challenged surrogate mothers was also
      sufficient to induce specific pharmacological and neuroanatomical abnormalities
      in the fostered offspring. Multiple schizophrenia-related dysfunctions emerging
      after prenatal immune challenge are thus mediated by prenatal but not postnatal
      maternal effects on the offspring, but immunological stress during pregnancy may
      affect postpartum maternal factors in such a way that being reared by an immune
      challenged surrogate mother can confer risk for distinct forms of psychopathology
      in adult life.

PMID- 17443131
TI  - D2 receptor occupancy of olanzapine pamoate depot using positron emission
      tomography: an open-label study in patients with schizophrenia.
AB  - A long-acting depot formulation of olanzapine that sustains plasma olanzapine
      concentrations for over a month after a single injection is currently under
      development. This multicenter, open-label study explored D(2) receptor occupancy
      of a fixed dose of olanzapine pamoate (OP) depot given every 4 weeks. Patients
      (nine male, five female) with schizophrenia or schizoaffective disorder
      previously stabilized on oral olanzapine were switched to OP depot 300 mg by
      intramuscular injection every 4 weeks for 6 months. No visitwise within-group
      significant changes were found in Brief Psychiatric Rating Scale Total or
      Clinical Global Impressions-Severity of Illness scores, although seven patients
      received oral olanzapine supplementation during the first four injection cycles.
      To minimize impact on D(2) occupancy, positron emission tomography (PET) scans
      were not completed during injection cycles that required supplemental oral
      olanzapine. Two patients reported transient injection site adverse events, which
      did not result in discontinuation. The most frequently reported treatment
      emergent adverse events were insomnia, aggravated psychosis, and anxiety. Mean
      striatal D(2) receptor occupancy, as measured by [(11)C]-raclopride PET, was 69%
      on oral olanzapine (5-20 mg/day) and 50% (trough) on OP depot at steady state.
      Following an initial decline, occupancy returned to 84% of baseline oral
      olanzapine occupancy after six injections. Over the study period, D(2) receptor
      occupancy and plasma olanzapine concentrations were significantly correlated
      (r=0.76, P</=0.001). OP depot resulted in mean D(2) receptor occupancy of
      approximately 60% or higher at the end of the 6-month study period, a level
      consistent with antipsychotic efficacy and found during treatment with oral
      olanzapine. However, supplemental oral olanzapine or another dosing strategy may
      be necessary to maintain adequate therapeutic response during the first few
      injection cycles.

PMID- 17443132
TI  - Pharmacokinetic and pharmacodynamic interactions between zolpidem and caffeine.
AB  - The kinetic and dynamic interaction of caffeine and zolpidem was evaluated in a
      double-blind, single-dose, six-way crossover study of 7.5 mg zolpidem (Z) or
      placebo (P) combined with low-dose caffeine (250 mg), high-dose caffeine (500
      mg), or placebo. Caffeine coadministration modestly increased maximum plasma
      concentration (C(max)) and area under the plasma concentration-time curve of
      zolpidem by 30-40%, whereas zolpidem did not significantly affect the
      pharmacokinetics of caffeine or its metabolites. Compared to P+P, Z+P
      significantly increased sedation, impaired digit-symbol substitution test
      performance, slowed tapping speed and reaction time, increased EEG relative beta
      amplitude, and impaired delayed recall. Caffeine partially, but not completely,
      reversed most pharmacodynamic effects of zolpidem. Thus, caffeine only
      incompletely reverses zolpidem's sedative and performance-impairing effects, and
      cannot be considered as an antidote to benzodiazepine agonists.

PMID- 17443133
TI  - Inhibition of PKC beta by ruboxistaurin does not enhance the acute blood pressure
      response to nitroglycerin.
AB  - Ruboxistaurin is a selective protein kinase C beta inhibitor undergoing clinical
      investigation for treatment of diabetic microvascular complications. This study
      assessed a possible blood pressure (BP) interaction between ruboxistaurin and the
      exogenous nitric oxide donor, glyceryl trinitrate (GTN). Subjects (N=22) with
      chronic stable angina received placebo or ruboxistaurin 96 mg/day orally to
      steady state in a crossover design. Graded GTN (0, 5, 10, 20, 40, 80, and 120
      microg/min) or 5% dextrose solution was then infused intravenously and BP was
      measured following each dose. Ruboxistaurin did not alter the slope of change in
      standing systolic BP (DeltasSBP/1n[GTN dose]) curve (P=0.272 analysis of
      covariance) or affect the DeltasSBP at the estimated GTN dose producing a 10-mm
      Hg reduction in sSBP from baseline on placebo (mean difference -0.9 mm Hg; 95%
      confidence of interval, -3.3-1.5). In conclusion, ruboxistaurin does not
      potentiate the acute BP-lowering effects of GTN.

PMID- 17443134
TI  - Cytochrome P450 3A5 genotype is associated with verapamil response in healthy
      subjects.
AB  - We hypothesized that CYP3A5 genotype contributes to the interindividual
      variability in verapamil response. Healthy subjects (n=26) with predetermined
      CYP3A5 genotypes were categorized as expressers (at least one CYP3A5(*)1 allele)
      and nonexpressers (subjects without a CYP3A5(*)1 allele). Verapamil
      pharmacokinetics and pharmacodynamics were determined after 7 days of dosing with
      240 mg daily. There was a significantly higher oral clearance of R-verapamil
      (165.1+/-86.4 versus 91.2+/-36.5 l/h; P=0.009) and S-verapamil (919.4+/-517.4
      versus 460.2+/-239.7 l/h; P=0.01) in CYP3A5 expressers compared to nonexpressers.
      Consequently, CYP3A5 expressers had significantly less PR-interval prolongation
      (19.5+/-12.3 versus 44.0+/-19.4 ms; P=0.0004), and had higher diastolic blood
      pressure (69.2+/-7.5 versus 61.6+/-5.1 mm Hg; P=0.036) than CYP3A5 nonexpressers
      after 7 days dosing with verapamil. CYP3A5 expressers display a greater steady
      state oral clearance of verapamil and may therefore experience diminished
      pharmacological effect of verapamil due to a greater steady state oral clearance.

PMID- 17443135
TI  - Novel nerve-agent antidote design based on crystallographic and mass
      spectrometric analyses of tabun-conjugated acetylcholinesterase in complex with
      antidotes.
AB  - Organophosphorus compound-based nerve agents inhibit the essential enzyme
      acetylcholinesterase (AChE) causing acute toxicity and death. Clinical treatment
      of nerve-agent poisoning is to use oxime-based antidotes to reactivate the
      inhibited AChE. However, the nerve agent tabun is resistant to oximes. To design
      improved oximes, crystal structures of a tabun-conjugated AChE in complex with
      different oximes are needed to guide the structural modifications of known
      antidotes. However, this type of structure is extremely challenging to obtain
      because both deamidation of the tabun conjugate and reactivation of AChE occur
      during crystallographic experiments. Here we report, for the first time, the
      crystal structures of Ortho-7 and HLo-7 in complex with AChE that is conjugated
      to an intact tabun. These structures were determined by our new strategy of
      combining crystallographic and mass spectrometric analyses of AChE crystals. The
      results explain the relative reactivation potencies of the two oximes and offer
      insights into improving known medical antidotes.

PMID- 17443136
TI  - Nuclear transport: target for therapy.
AB  - Drugs directed at plasma membrane receptors target environment-cell interactions
      and are the mainstay of clinical pharmacology. Decoding mechanisms that govern
      intracellular signaling has recently opened new therapeutic avenues for
      interventions at cytosol-organellar interfaces. The nuclear envelope and nuclear
      transport machinery have emerged central in the discovery and development of
      experimental therapeutics capable of modulating cellular genetic programs.
      Insight into nucleocytoplasmic exchange has unmasked promising anticancer,
      antiviral, and anti-inflammatory strategies.

PMID- 17443140
TI  - Plus ca change?

PMID- 17443141
TI  - Addicted to secrecy.

PMID- 17443144
TI  - Colliders race for the Higgs.

PMID- 17443145
TI  - Evidence for fourth neutrino fades.

PMID- 17443142
TI  - Small steps forward.

PMID- 17443146
TI  - Interim view from NASA relativity probe.

PMID- 17443148
TI  - Ozone sensor to be reinstated.

PMID- 17443147
TI  - Court case to reclaim confidential data.

PMID- 17443149
TI  - Make way for monkeys.

PMID- 17443151
TI  - Chimps lead evolutionary race.

PMID- 17443152
TI  - Stem-cell issue moves up the US agenda.

PMID- 17443154
TI  - Moment of reckoning.

PMID- 17443157
TI  - French election: the candidates respond.

PMID- 17443158
TI  - French election: let science speak for itself.

PMID- 17443159
TI  - French election: is French science in decline...

PMID- 17443160
TI  - Who will start the 3Rs ball rolling for animal welfare?

PMID- 17443161
TI  - Why do so few women speak at science meetings?

PMID- 17443162
TI  - Law and research could add up to profitable niche drugs.

PMID- 17443163
TI  - Other riffs on cooperation are already showing how well a wiki could work.

PMID- 17443168
TI  - Rules of engagement.

PMID- 17443169
TI  - Palaeobotany: a tree without leaves.

PMID- 17443171
TI  - Earth science: when crust is bred.

PMID- 17443172
TI  - RNA silencing: genomic defence with a slice of pi.

PMID- 17443174
TI  - Quantum mechanics: to be or not to be local.

PMID- 17443173
TI  - Neurobiology: feeling right about doing right.

PMID- 17443175
TI  - Cell biology: the checkpoint brake relieved.

PMID- 17443177
TI  - Social science: the urban organism.

PMID- 17443178
TI  - Obituary: Donald E. Osterbrock (1924-2007).

PMID- 17443179
TI  - An experimental test of non-local realism.
AB  - Most working scientists hold fast to the concept of 'realism'--a viewpoint
      according to which an external reality exists independent of observation. But
      quantum physics has shattered some of our cornerstone beliefs. According to
      Bell's theorem, any theory that is based on the joint assumption of realism and
      locality (meaning that local events cannot be affected by actions in space-like
      separated regions) is at variance with certain quantum predictions. Experiments
      with entangled pairs of particles have amply confirmed these quantum predictions,
      thus rendering local realistic theories untenable. Maintaining realism as a
      fundamental concept would therefore necessitate the introduction of 'spooky'
      actions that defy locality. Here we show by both theory and experiment that a
      broad and rather reasonable class of such non-local realistic theories is
      incompatible with experimentally observable quantum correlations. In the
      experiment, we measure previously untested correlations between two entangled
      photons, and show that these correlations violate an inequality proposed by
      Leggett for non-local realistic theories. Our result suggests that giving up the
      concept of locality is not sufficient to be consistent with quantum experiments,
      unless certain intuitive features of realism are abandoned.

PMID- 17443181
TI  - Iron meteorite evidence for early formation and catastrophic disruption of
      protoplanets.
AB  - In our Solar System, the planets formed by collisional growth from smaller
      bodies. Planetesimals collided to form Moon-to-Mars-sized protoplanets in the
      inner Solar System in 0.1-1 Myr, and these collided more energetically to form
      planets. Insights into the timing and nature of collisions during planetary
      accretion can be gained from meteorite studies. In particular, iron meteorites
      offer the best constraints on early stages of planetary accretion because most
      are remnants of the oldest bodies, which accreted and melted in <1.5 Myr, forming
      silicate mantles and iron-nickel metallic cores. Cooling rates for various groups
      of iron meteorites suggest that if the irons cooled isothermally in the cores of
      differentiated bodies, as conventionally assumed, these bodies were 5-200 km in
      diameter. This picture is incompatible, however, with the diverse cooling rates
      observed within certain groups, most notably the IVA group, but the large
      uncertainties associated with the measurements do not preclude it. Here we report
      cooling rates for group IVA iron meteorites that range from 100 to 6,000 K Myr(
      1), increasing with decreasing bulk Ni. Improvements in the cooling rate model,
      smaller error bars, and new data from an independent cooling rate indicator show
      that the conventional interpretation is no longer viable. Our results require
      that the IVA meteorites cooled in a 300-km-diameter metallic body that lacked an
      insulating mantle. This body probably formed approximately 4,500 Myr ago in a
      'hit-and-run' collision between Moon-to-Mars-sized protoplanets. This
      demonstrates that protoplanets of approximately 10(3) km size accreted within the
      first 1.5 Myr, as proposed by theory, and that fragments of these bodies survived
      as asteroids.

PMID- 17443180
TI  - Anaphase initiation is regulated by antagonistic ubiquitination and
      deubiquitination activities.
AB  - The spindle checkpoint prevents chromosome mis-segregation by delaying sister
      chromatid separation until all chromosomes have achieved bipolar attachment to
      the mitotic spindle. Its operation is essential for accurate chromosome
      segregation, whereas its dysregulation can contribute to birth defects and
      tumorigenesis. The target of the spindle checkpoint is the anaphase-promoting
      complex (APC), a ubiquitin ligase that promotes sister chromatid separation and
      progression to anaphase. Using a short hairpin RNA screen targeting components of
      the ubiquitin-proteasome pathway in human cells, we identified the
      deubiquitinating enzyme USP44 (ubiquitin-specific protease 44) as a critical
      regulator of the spindle checkpoint. USP44 is not required for the initial
      recognition of unattached kinetochores and the subsequent recruitment of
      checkpoint components. Instead, it prevents the premature activation of the APC
      by stabilizing the APC-inhibitory Mad2-Cdc20 complex. USP44 deubiquitinates the
      APC coactivator Cdc20 both in vitro and in vivo, and thereby directly counteracts
      the APC-driven disassembly of Mad2-Cdc20 complexes (discussed in an accompanying
      paper). Our findings suggest that a dynamic balance of ubiquitination by the APC
      and deubiquitination by USP44 contributes to the generation of the switch-like
      transition controlling anaphase entry, analogous to the way that phosphorylation
      and dephosphorylation of Cdk1 by Wee1 and Cdc25 controls entry into mitosis.

PMID- 17443182
TI  - A quantum scattering interferometer.
AB  - The collision of two ultracold atoms results in a quantum mechanical
      superposition of the two possible outcomes: each atom continues without
      scattering, and each atom scatters as an outgoing spherical wave with an s-wave
      phase shift. The magnitude of the s-wave phase shift depends very sensitively on
      the interaction between the atoms. Quantum scattering and the underlying phase
      shifts are vitally important in many areas of contemporary atomic physics,
      including Bose-Einstein condensates, degenerate Fermi gases, frequency shifts in
      atomic clocks and magnetically tuned Feshbach resonances. Precise experimental
      measurements of quantum scattering phase shifts have not been possible because
      the number of scattered atoms depends on the s-wave phase shifts as well as the
      atomic density, which cannot be measured precisely. Here we demonstrate a
      scattering experiment in which the quantum scattering phase shifts of individual
      atoms are detected using a novel atom interferometer. By performing an atomic
      clock measurement using only the scattered part of each atom's wavefunction, we
      precisely measure the difference of the s-wave phase shifts for the two clock
      states in a density-independent manner. Our method will enable direct and precise
      measurements of ultracold atom-atom interactions, and may be used to place
      stringent limits on the time variations of fundamental constants.

PMID- 17443183
TI  - Regioselective one-pot protection of carbohydrates.
AB  - Carbohydrates are involved in a wide range of biological processes. These
      structurally diverse compounds are more complex than other biological polymers,
      and are often present as heterogeneous mixtures in nature. The chemical synthesis
      of carbohydrates is one way to obtain pure oligosaccharides, but it is hampered
      by difficulties associated with the regioselective protection of polyhydroxyls
      and challenges related to the stereoselective assembly of glycosidic linkages.
      Here we describe a combinatorial, and highly-regioselective, method that can be
      used to protect individual hydroxy groups of a monosaccharide. This approach can
      be used to install an orthogonal protecting group pattern in a single reaction
      vessel (a 'one-pot' reaction), which removes the need to carry out the time
      consuming isolation and purification of intermediates. Hundreds of building
      blocks have been efficiently prepared starting from d-glucose, and the iterative
      coupling of these building blocks enabled us to assemble beta-1,6-glucans and a
      library of oligosaccharides based on the influenza-virus-binding trisaccharide.

PMID- 17443184
TI  - Helium isotopic evidence for episodic mantle melting and crustal growth.
AB  - The timing of formation of the Earth's continental crust is the subject of a long
      standing debate, with models ranging from early formation with little subsequent
      growth, to pulsed growth, to steadily increasing growth. But most models do agree
      that the continental crust was extracted from the mantle by partial melting. If
      so, such crustal extraction should have left a chemical fingerprint in the
      isotopic composition of the mantle. The subduction of oceanic crust and
      subsequent convective mixing, however, seems to have largely erased this record
      in most mantle isotopic systems (for example, strontium, neodymium and lead). In
      contrast, helium is not recycled into the mantle because it is volatile and
      degasses from erupted oceanic basalts. Therefore helium isotopes may potentially
      preserve a clearer record of mantle depletion than recycled isotopes. Here I show
      that the spectrum of 4He/3He ratios in ocean island basalts appears to preserve
      the mantle's depletion history, correlating closely with the ages of proposed
      continental growth pulses. The correlation independently predicts both the
      dominant 4He/3He peak found in modern mid-ocean-ridge basalts, as well as
      estimates of the initial 4He/3He ratio of the Earth. The correspondence between
      the ages of mantle depletion events and pulses of crustal production implies that
      the formation of the continental crust was indeed episodic and punctuated by
      large, potentially global, melting events. The proposed helium isotopic evolution
      model does not require a primitive, undegassed mantle reservoir, and therefore is
      consistent with whole mantle convection.

PMID- 17443185
TI  - Giant cladoxylopsid trees resolve the enigma of the Earth's earliest forest
      stumps at Gilboa.
AB  - The evolution of trees of modern size growing together in forests fundamentally
      changed terrestrial ecosystems. The oldest trees are often thought to be of
      latest Devonian age (about 380-360 Myr old) as indicated by the widespread
      occurrence of Archaeopteris (Progymnospermopsida). Late Middle Devonian fossil
      tree stumps, rooted and still in life position, discovered in the 1870s from
      Gilboa, New York, and later named Eospermatopteris, are widely cited as evidence
      of the Earth's 'oldest forest'. However, their affinities and significance have
      proved to be elusive because the aerial portion of the plant has been unknown
      until now. Here we report spectacular specimens from Schoharie County, New York,
      showing an intact crown belonging to the cladoxylopsid Wattieza
      (Pseudosporochnales) and its attachment to Eospermatopteris trunk and base. This
      evidence allows the reconstruction of a tall (at least 8 m), tree-fern-like plant
      with a trunk bearing large branches in longitudinal ranks. The branches were
      probably abscised as frond-like modules. Lower portions of the trunk show
      longitudinal carbonaceous strands typical of Eospermatopteris, and a flat bottom
      with many small anchoring roots. These specimens provide new insight into Earth's
      earliest trees and forest ecosystems. The tree-fern-like morphology described
      here is the oldest example so far of an evolutionarily recurrent arborescent body
      plan within vascular plants. Given their modular construction, these plants
      probably produced abundant litter, indicating the potential for significant
      terrestrial carbon accumulation and a detritus-based arthropod fauna by the
      Middle Devonian period.

PMID- 17443186
TI  - Ubiquitination by the anaphase-promoting complex drives spindle checkpoint
      inactivation.
AB  - Eukaryotic cells rely on a surveillance mechanism known as the spindle checkpoint
      to ensure accurate chromosome segregation. The spindle checkpoint prevents sister
      chromatids from separating until all kinetochores achieve bipolar attachments to
      the mitotic spindle. Checkpoint proteins tightly inhibit the anaphase-promoting
      complex (APC), a ubiquitin ligase required for chromosome segregation and
      progression to anaphase. Unattached kinetochores promote the binding of
      checkpoint proteins Mad2 and BubR1 to the APC-activator Cdc20, rendering it
      unable to activate APC. Once all kinetochores are properly attached, however,
      cells inactivate the checkpoint within minutes, allowing for the rapid and
      synchronous segregation of chromosomes. How cells switch from strong APC
      inhibition before kinetochore attachment to rapid APC activation once attachment
      is complete remains a mystery. Here we show that checkpoint inactivation is an
      energy-consuming process involving APC-dependent multi-ubiquitination. Multi
      ubiquitination by APC leads to the dissociation of Mad2 and BubR1 from Cdc20, a
      process that is reversed by a Cdc20-directed de-ubiquitinating enzyme. The mutual
      regulation between checkpoint proteins and APC leaves the cell poised for rapid
      checkpoint inactivation and ensures that chromosome segregation promptly follows
      the completion of kinetochore attachment. In addition, our results suggest a
      mechanistic basis for how cancer cells can have a compromised spindle checkpoint
      without corresponding mutations in checkpoint genes.

PMID- 17443187
TI  - A stepwise mechanism for acetylcholine receptor channel gating.
AB  - Muscle contraction is triggered by the opening of acetylcholine receptors at the
      vertebrate nerve-muscle synapse. The M2 helix of this allosteric membrane protein
      lines the channel, and contains a 'gate' that regulates the flow of ions through
      the pore. We used single-molecule kinetic analysis to probe the transition state
      of the gating conformational change and estimate the relative timing of M2
      motions in the alpha-subunit of the murine acetylcholine receptor. This analysis
      produces a 'Phi-value' for a given residue that reflects its open-like versus
      closed-like character at the transition state. Here we show that most of the
      residues throughout the length of M2 have a Phi-value of approximately 0.64 but
      that some near the middle have lower Phi-values of 0.52 or 0.31, suggesting that
      alphaM2 moves in three discrete steps. The core of the channel serves both as a
      gate that regulates ion flow and as a hub that directs the propagation of the
      gating isomerization through the membrane domain of the acetylcholine receptor.

PMID- 17443190
TI  - Cell biology: close-up on cell biology.

PMID- 17443193
TI  - Image statistics and the perception of surface qualities.
AB  - The world is full of surfaces, and by looking at them we can judge their material
      qualities. Properties such as colour or glossiness can help us decide whether a
      pancake is cooked, or a patch of pavement is icy. Most studies of surface
      appearance have emphasized textureless matte surfaces, but real-world surfaces,
      which may have gloss and complex mesostructure, are now receiving increased
      attention. Their appearance results from a complex interplay of illumination,
      reflectance and surface geometry, which are difficult to tease apart given an
      image. If there were simple image statistics that were diagnostic of surface
      properties it would be sensible to use them. Here we show that the skewness of
      the luminance histogram and the skewness of sub-band filter outputs are
      correlated with surface gloss and inversely correlated with surface albedo
      (diffuse reflectance). We find evidence that human observers use skewness, or a
      similar measure of histogram asymmetry, in making judgements about surfaces. When
      the image of a surface has positively skewed statistics, it tends to appear
      darker and glossier than a similar surface with lower skewness, and this is true
      whether the skewness is inherent to the original image or is introduced by
      digital manipulation. We also find a visual after-effect based on skewness:
      adaptation to patterns with skewed statistics can alter the apparent lightness
      and glossiness of surfaces that are subsequently viewed. We suggest that there
      are neural mechanisms sensitive to skewed statistics, and that their outputs can
      be used in estimating surface properties.

PMID- 17443194
TI  - Visual perception: a gloss on surface properties.

PMID- 17443195
TI  - Early human milk feeding is associated with a lower risk of necrotizing
      enterocolitis in very low birth weight infants.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is a frequent cause of mortality and
      morbidity in very low birth weight (VLBW) infants. Human milk (HM) feeding has
      been associated with lower risk of NEC. However, mothers of VLBW infants often
      experience insufficient milk production, resulting in mixed feedings of HM and
      formula. Moreover, medical complications often limit the volume of feeding they
      can be given. OBJECTIVE: To determine if high proportions of (50% or greater) HM
      enteral feeding within the first 14 days of life are protective against NEC.
      METHOD: This was a prospective cohort study of VLBW infants who were grouped
      according to the HM proportion of enteral feeding in the first 14 days: <50% (low
      human milk, LHM, n=46) and > or =50% (high human milk, HHM, n=156). The outcome
      of interest was development of NEC (Bell stage 2 or 3). Logistic regression was
      used to estimate odds ratios (OR) and 95% confidence intervals (CI) and to assess
      potential confounding due to perinatal risk factors. RESULT: Two hundred and two
      infants were studied. Confirmed NEC occurred in 5/46 (10.6%) of the LHM group, as
      compared with 5/156 (3.2%) of the HHM. Gestational age was the only perinatal
      factor associated with risk of NEC. After adjustment for gestational age, HHM was
      associated with a lower risk of NEC ((OR=0.17, 95% CI: 0.04 to 0.68), P=0.01).
      CONCLUSION: Enteral feeding containing at least 50% HM in the first 14 days of
      life was associated with a sixfold decrease in the odds of NEC.

PMID- 17443196
TI  - Infant end-of-life care: the parents' perspective.
AB  - OBJECTIVE: The purpose of this study was to identify factors important to parents
      in their infant's end-of-life care. STUDY DESIGN: Participants were parents (n=19
      families) whose infant (less than 1 year old) had died. Parents completed the
      Revised Grief Experience Inventory (RGEI) and a semi-structured interview
      regarding their infant's end-of-life care. Interviews were rated using the Post
      Death Adaptation Scale (PDAS). RESULTS: Parents scored significantly lower than
      the normative sample on the RGEI, and PDAS scores suggested that these parents
      were adapting positively. Parent interviews identified the aspects of care that
      were important to parents: honesty, empowered decision-making, parental care,
      environment, faith/trust in nursing care, physicians bearing witness and support
      from other hospital care providers. CONCLUSIONS: Results of this study suggest
      that parents can effectively cope following the death of an infant and the
      medical staff can do much to improve the end-of-life care for infants and their
      families.

PMID- 17443197
TI  - Hypoxic respiratory failure: etiology and outcomes at one referral center 2000
      through 2005.
AB  - OBJECTIVE: We calculated in a referral population of term and near-term infants
      with hypoxic respiratory failure (HRF) as a primary presenting problem the
      overall survival rate, the need for extracorporeal membrane oxygenation (ECMO)
      and the incidence of apparently irreversible disorders. STUDY DESIGN: All infants
      >or=36-week gestation admitted at <or=72 h of age from 2000 through 2005 were
      identified. The worst (highest) oxygen index (OI) was calculated and outcomes
      were noted. RESULTS: A total of 630 infants were reviewed and 315 infants were
      identified with primary diagnosis of HRF; four infants died before discharge. One
      hundred seventy-seven infants had OI <or=14; 71 had OI of 15 to 25; and 67 had OI
      of >25. A total of 32 infants received ECMO, including all four who died, two
      with histologic evidence of pulmonary malformations and two with septic shock.
      CONCLUSION: Term or near-term infants with isolated HRF are likely to survive,
      given the low incidence of pulmonary disorders not supportable by inhaled nitric
      oxide or ECMO.

PMID- 17443198
TI  - Association between early postnatal weight loss and death or BPD in small and
      appropriate for gestational age extremely low-birth-weight infants.
AB  - OBJECTIVE: To examine the association between weight loss during the first 10
      days of life and the incidence of death or bronchopulmonary dysplasia (BPD) in
      small for gestational age (SGA) and appropriate for gestational age (AGA)
      extremely low-birth-weight infants. DESIGN/METHODS: This is a retrospective
      analysis of a cohort of ELBW (birth weight <1000 g) infants from the NICHD
      Neonatal Research Network's database. The cohort consisted of 9461 ELBW infants
      with gestational age of 24-29 weeks, admitted to Network's participating centers
      during calendar years 1994-2002 and surviving at least 72 h after birth. The
      cohort was divided into two groups, 1248 SGA (with birth weight below 10th
      percentile for gestational age) and 8213 AGA (with birth weight between 10th and
      90th percentile) infants. We identified infants with or without weight loss
      during the first 10 days of life, which we termed as 'early postnatal weight
      loss' (EPWL). Univariate analyses were used to predict whether EPWL was related
      to the primary outcome, death or BPD, within each birth weight/gestation category
      (SGA or AGA). BPD and death were also analyzed separately in relation to EPWL.
      Logistic regression analysis was done to evaluate the risk of death or BPD in SGA
      and AGA groups, controlling for maternal and neonatal demographic and clinical
      factors found to be significant by univariate analysis. RESULTS: SGA ELBW infants
      had a lower prevalence of EPWL as compared with AGA ELBW infants (81.2 vs 93.7%,
      respectively, P<0.001). In AGA infants, univariate analysis showed that death or
      BPD rate was lower in the group of infants with EPWL compared with infants
      without EPWL (53.4 vs 74.3%, respectively, P<0.001). The BPD (47.2 vs 64%,
      P<0.001) and death (13.8 vs 32.9%, P<0.001) rate were similarly lower in the EPWL
      group. The risk-adjusted odds ratios (ORs) showed that EPWL was associated with
      lower rate of death or BPD (OR 0.47, 95% CI: 0.37-0.60). In SGA infants, on
      univariate analysis, a similar association between EPWL and outcomes was seen as
      shown in AGA infants: death or BPD (55.9 vs 75.2%, P<0.001), BPD rate (48.3 vs
      62.1%, P=0.002) and rate death (19 vs 40.8%, P<0.001) for those with or without
      EPWL, respectively. Multiple logistic regression showed that as in AGA ELBW
      infants, EPWL was associated with lower risk for death or BPD (OR 0.60, 95% CI:
      0.41-0.89) among SGA infants. CONCLUSIONS: SGA infants experienced less EPWL when
      compared with their AGA counterparts. EPWL was associated with a lower risk of
      death or BPD in both ELBW AGA and SGA infants. These data suggest that clinicians
      who consider the association between EPWL and risk of death or BPD should do so
      independent of gestation/birth weight status.

PMID- 17443199
TI  - Elevated total peripheral leukocyte count may identify risk for neurological
      disability in asphyxiated term neonates.
AB  - OBJECTIVE: The present study investigated the relationship between neurologic
      outcome and total circulating white blood cell (WBC) and absolute neutrophil
      counts (ANCs) in the first week of life in term infants with hypoxic-ischemic
      encephalopathy (HIE). STUDY DESIGN: Long-term neurologic outcome at 18 months was
      measured retrospectively in 30 term neonates with HIE using the Pediatric
      Cerebral Performance Category Scale (PCPCS) score with outcomes dichotomized as
      either good or poor. We then compared white blood cell and ANC levels during the
      first 4 days of life and magnetic resonance imaging (MRI) obtained within the
      first month life between the two PCPCS groups. MRI was quantified using a
      validated scoring system. RESULTS: Neonates with good long-term outcomes had
      significantly lower MRI scores (indicating lesser injury) than neonates with poor
      outcomes. More importantly, neonates with poor outcomes had significantly higher
      WBC and ANC levels as early as12 h after birth and up to 96 h after birth
      compared to those with good outcomes. These data suggest that elevated peripheral
      neutrophil counts in the first 96 h of life may signal or predict adverse long
      term outcome. CONCLUSIONS: Our findings suggest that elevated peripheral
      neutrophil counts in the first 96 h of life in term infants with HIE may
      contribute to abnormal neurodevelopmental outcome.

PMID- 17443200
TI  - Is refractory hypotension in preterm infants a manifestation of early ductal
      shunting?
AB  - BACKGROUND: Clinicians frequently use hydrocortisone (HC) to treat vasopressor
      resistant hypotension even before establishing its cause. OBJECTIVE: To identify
      the etiologic factors leading to development of refractory hypotension, and to
      assess if patent ductus arteriosus (PDA) is associated with refractory
      hypotension during the first week of life. STUDY DESIGN: The medical records of
      290 consecutively born infants <or=30 weeks' gestational age (GA) were reviewed
      to identify the escalating need for vasopressors to maintain mean arterial blood
      pressure (MABP) at or above a level equal to the GA in completed weeks.
      Refractory hypotension was defined as MABP unresponsive to fluid boluses and high
      dose vasopressors (dopamine and dobutamine at doses 20 microg/kg/min each and/or
      epinephrine) prompting the use of HC. RESULTS: Eighty-nine (30.7%) of 290 infants
      had refractory hypotension between postnatal days 2 and 7. Infants with
      refractory hypotension were more likely to have a lower birth weight and GA
      (P<0.001), been treated with surfactant (P=0.004) and received indomethacin for a
      symptomatic PDA (P<0.001). To identify the etiologic factors, a univariate
      analysis revealed that the use of high-frequency oscillatory ventilation,
      presence of air leaks, PDA, sepsis, hyperkalemia and intraventricular hemorrhage
      (IVH) were significantly associated with refractory hypotension. However,
      multivariate analysis confirmed the independent association of only PDA (odds
      ratio (OR) 7.6, 95% confidence interval (CI) 3.3-17.7, P=0.000), severe IVH (OR
      2.6, 95% CI 1.1-6.4, P=0.03) and GA (OR 0.7, 95% CI 0.6-0.8, P=0.001).
      CONCLUSIONS: Evaluation for early ductal shunting and closure of the ductus, if
      patent, should be attempted before HC is considered in hypotensive infants with
      escalating needs for vasopressors.

PMID- 17443201
TI  - Increased hemolysis from saline pre-washing RBCs or centrifugal pumps in neonatal
      ECMO.
AB  - OBJECTIVES: Hemolysis is a significant complication of extracorporeal membrane
      oxygenation (ECMO), with a reported incidence of 12.2%. The aims of this study
      were (1) to investigate hemolysis caused by saline-washed versus unwashed RBCs,
      (2) to determine in vitro the effects of saline washing on erythrocyte hemolytic
      markers and (3) to investigate hemolysis by centrifugal versus roller pumps.
      STUDY DESIGN: (1) To evaluate the effect of pre-transfusion saline-washing versus
      non-washing, the peak plasma-free hemoglobin (FHb) and total bilirubin in the
      first 3 days versus the next 4 days of ECMO were compared (2) Pre- and postsaline
      washed RBCs were analyzed for K+ hemoglobin, mean corpuscular volume, FHb and
      hemolysis at baseline and after 4 h of storage at 4 degrees C. (3) Over 10 000
      neonatal ECMO cases were retrospectively reviewed to study the effect of pump
      type on hemolysis. RESULTS: (1) The washed blood group had significantly more
      hemolysis within the first 3 days of ECMO. (2) Immediately after saline washing,
      the K+ and Hb concentrations were significantly decreased compared with unwashed
      blood, and these differences were maintained after 4 h. The osmotic fragility of
      washed RBCs after 4 h of storage at 4 degrees C was significantly higher than at
      baseline. (3) Hemolysis was reported more often in the centrifugal than in the
      roller pump group. CONCLUSIONS: (1) Using unwashed RBCs decreased hemolysis
      within the first 3 days of ECMO. (2) Saline washing, while decreasing the
      concentration of K+ in the plasma, significantly increases RBC membrane osmotic
      fragility. (3) Hemolysis is linked to the use of centrifugal pumps.

PMID- 17443202
TI  - Severe early onset pre-eclampsia: prognostic value of ultrasound and Doppler
      assessment.
AB  - OBJECTIVE: Assess the prognostic value of ultrasound and Doppler parameters in
      severe preterm pre-eclampsia. STUDY DESIGN: Prospective cohort study in Cape
      Town, South Africa, involving 113 women with severe pre-eclampsia between 24 and
      34 weeks of gestation and managed expectantly when suitable. Serial ultrasound
      and multivessel Doppler assessments were performed 2 to 3 times weekly.
      Observations included fetal weight estimation, growth pattern, amniotic fluid
      volume, appearance of the heart and bowel, pulsatility index of the uterine,
      umbilical and middle cerebral arteries and ductus venosus. Perinatal outcome
      (death or neurological compromise, n=12) and major morbidity (n=62) were related
      to findings at recruitment and on the last assessment preceding delivery.
      RESULTS: In univariate analysis, fetal growth asymmetry and waveform analysis of
      all three fetal vessels significantly correlated with both end points. The
      initial fetal weight estimation with a cutoff weight of 1080 g had the highest
      sensitivity (83.3%) and negative predictive value (97.5%) for poor outcome
      (P<0.001) while the final ductus venosus pulsatility index had the highest
      specificity (92%) and positive predictive value (33%). The combination of a
      raised placentocerebral ratio and ductus venosus pulsatility index close to
      delivery had the highest (57.1%) positive predictive value. Logistic regression
      showed the best overall predictive model for poor outcome to be a combination of
      initial fetal weight estimation and final ductus venosus pulsatility index
      (overall accuracy 94.6%, RR 20.20 (7.36, 55.41)). The initial fetal weight
      estimation with a cutoff weight of 1283 g provided the best correct prediction of
      major morbidity (83.2% overall accuracy, sensitivity 79.0%, specificity 88.2%,
      positive and negative predictive values of 89.1 and 77.6% respectively). This was
      better than using the gestational age at recruitment or delivery, birth weight or
      any of the Doppler results. The prediction of morbidity was not improved by the
      addition of any other variable in logistic regression analysis. CONCLUSION: For
      the short-term outcome measures assessed in this study, the estimated fetal
      weight at the time of diagnosis is the most important prognostic factor in severe
      pre-eclampsia with some additional value of ductus venosus assessment.

PMID- 17443203
TI  - Low-molecular-weight heparin in pregnancy: peripartum bleeding complications.
AB  - OBJECTIVE: To compare bleeding complications in pregnant patients treated with
      low-molecular-weight heparin (LMWH) to untreated controls. STUDY DESIGN: A case
      control study of patients from 2001 to 2005 who received prophylactic or
      therapeutic doses of LMWH during pregnancy was carried out. Indications for LMWH
      included current or prior thromboembolism, thrombophilia, or heart valve
      replacement. Controls were chosen in a 2:1 ratio to cases, matched for delivery
      route, and selected as the next two consecutive deliveries. The primary outcome
      was postpartum hemorrhage (PPH). Odds ratios (ORs) were calculated with 95%
      confidence intervals (CIs). RESULTS: Forty-nine women treated with LMWH delivered
      55 infants. Current or prior thromboembolic disease was the anticoagulation
      indication in 15/55 (27.3%) and 26/55 (47%) of pregnancies, respectively. There
      were more obese gravidas (OR 3.91, CI 1.70 to 9.09) and labor induction was more
      common in the LMWH group, 25/55 (45%) vs 29/110 (26%), P=0.01. There was no
      difference in estimated blood loss (295.7+/-145.7 vs 308.6+/-111.9 cm(3), P=0.62
      vaginal; 687.5+/-251.8 vs 765.0+/-313.2 cm(3), P=0.34 cesarean), PPH (6/55, 11%
      vs 9/110, 8.2% OR 1.37, CI 0.16 to 11.5) or transfusion (3/55, 5.4% vs 4/110,
      3.6% OR 1.50, CI 0.3 to 7.48) between the cases and controls. There were two
      cases of postpartum pulmonary emboli, one with a maternal mortality. CONCLUSION:
      Bleeding complications, including PPH and transfusion, in patients treated with
      LMWH during pregnancy were not increased when compared to normal controls matched
      for delivery route.

PMID- 17443204
TI  - Inhaled nitric oxide in infants >1500 g and <34 weeks gestation with severe
      respiratory failure.
AB  - OBJECTIVE: Inhaled nitric oxide (iNO) use in infants >1500 g, but <34 weeks
      gestation with severe respiratory failure will reduce the incidence of death
      and/or bronchopulmonary dysplasia (BPD). STUDY DESIGN: Infants born at <34 weeks
      gestation with a birth weight >1500 g with respiratory failure were randomly
      assigned to receive placebo or iNO. RESULTS: Twenty-nine infants were randomized.
      There were no differences in baseline characteristics, but the status at
      randomization showed a statistically significant difference in the use of high
      frequency ventilation (P=0.03). After adjustment for oxygenation index entry
      strata, there was no difference in death and/or BPD (adjusted relative risk (RR)
      0.80, 95% confidence interval (CI) 0.43 to 1.48; P=0.50), death (adjusted RR
      1.26, 95% CI 0.47 to 3.41; P=0.65) or BPD (adjusted RR 0.40, 95% CI 0.47 to 3.41;
      P=0.21). CONCLUSIONS: Although sample size limits our ability to make definitive
      conclusions, this small pilot trial of iNO use in premature infants >1500 g and
      <34 weeks with severe respiratory failure suggests that iNO does not affect the
      rate of BPD and/or death.

PMID- 17443205
TI  - Increased consumption of fruit and vegetables is related to a reduced risk of
      coronary heart disease: meta-analysis of cohort studies.
AB  - Increased consumption of fruit and vegetables has been shown to be associated
      with a reduced risk of coronary heart disease (CHD) in many epidemiological
      studies, however, the extent of the association is uncertain. We quantitatively
      assessed the relation between fruit and vegetable intake and incidence of CHD by
      carrying out a meta-analysis of cohort studies. Studies were included if they
      reported relative risks (RRs) and corresponding 95% confidence interval (CI) of
      CHD with respect to frequency of fruit and vegetable intake. Twelve studies,
      consisting of 13 independent cohorts, met the inclusion criteria. There were
      278,459 individuals (9143 CHD events) with a median follow-up of 11 years.
      Compared with individuals who had less than 3 servings/day of fruit and
      vegetables, the pooled RR of CHD was 0.93 (95% CI: 0.86-1.00, P=0.06) for those
      with 3-5 servings/day and 0.83 (0.77-0.89, P<0.0001) for those with more than 5
      servings/day. Subgroup analyses showed that both fruits and vegetables had a
      significant protective effect on CHD. Our meta-analysis of prospective cohort
      studies demonstrates that increased consumption of fruit and vegetables from less
      than 3 to more than 5 servings/day is related to a 17% reduction in CHD risk,
      whereas increased intake to 3-5 servings/day is associated with a smaller and
      borderline significant reduction in CHD risk. These results provide strong
      support for the recommendations to consume more than 5 servings/day of fruit and
      vegetables.

PMID- 17443206
TI  - GenSalt: rationale, design, methods and baseline characteristics of study
      participants.
AB  - Hypertension is a complex disorder influenced by genetic and environmental
      determinants and their interactions. The objectives of the Genetic Epidemiology
      Network of Salt Sensitivity (GenSalt) are to localize and identify genes related
      to blood pressure (BP) responses to dietary sodium and potassium intervention.
      GenSalt utilizes a family feeding-study design. Each family was ascertained
      through a proband with untreated prehypertension or stage-1 hypertension in rural
      China. A medical history, lifestyle risk factors and responses to cold pressor
      tests, were obtained at baseline visits while BP, weight, blood and urine
      specimens were collected at baseline and follow-up visits. The dietary
      intervention included a 7-day low-sodium feeding (51.3 mmol/day), a 7-day high
      sodium feeding (307.8 mmol/day) and a 7-day high-sodium feeding with an oral
      potassium supplementation (60 mmol/day). Microsatellite markers for genome-wide
      linkage scan and single nucleotide polymorphism (SNP) markers in candidate genes
      will be genotyped. Overall, 3153 participants from 658 families were recruited
      for GenSalt. The mean systolic and diastolic BPs were 128.0 and 80.3, 111.6 and
      71.0, 112.6 and 72.6, 106.6 and 65.3 and 136.7 and 75.0 mm Hg for probands,
      siblings, spouses, offspring and parents, respectively. The mean urinary
      excretion of sodium and potassium were 232.5 and 38.6, 222.9 and 38.2, 213.1 and
      37.8 and 207.3 and 36.0 mmol/24-h for probands, siblings, spouses and offspring,
      respectively. Our study will identify novel genes that influence significantly
      the effect of dietary sodium and potassium intake on BP. This information is
      useful for development of targeted intervention for the prevention and treatment
      of hypertension.

PMID- 17443207
TI  - Stroke, with or with no ice? Observations on amphetamine for the management of
      acute stroke.

PMID- 17443208
TI  - Amphetamine increases blood pressure and heart rate but has no effect on motor
      recovery or cerebral haemodynamics in ischaemic stroke: a randomized controlled
      trial (ISRCTN 36285333).
AB  - Amphetamine enhances recovery after experimental ischaemia and has shown promise
      in small clinical trials when combined with motor or sensory stimulation.
      Amphetamine, a sympathomimetic, might have haemodynamic effects in stroke
      patients, although limited data have been published. Subjects were recruited 3-30
      days post-ischaemic stroke into a phase II randomized (1:1), double-blind,
      placebo-controlled trial. Subjects received dexamphetamine (5 mg initially, then
      10 mg for 10 subsequent doses with 3- or 4-day separations) or placebo in
      addition to inpatient physiotherapy. Recovery was assessed by motor scales (Fugl
      Meyer (FM)), and functional scales (Barthel index (BI) and modified Rankin score
      (mRS)). Peripheral blood pressure (BP), central haemodynamics and middle cerebral
      artery blood flow velocity were assessed before, and 90 min after, the first two
      doses. Thirty-three subjects were recruited, aged 33-88 (mean 71) years, males
      52%, 4-30 (median 15) days post stroke to inclusion. Sixteen patients were
      randomized to placebo and seventeen to amphetamine. Amphetamine did not improve
      motor function at 90 days; mean (s.d.) FM 37.6 (27.6) vs control 35.2 (27.8)
      (P=0.81). Functional outcome (BI, mRS) did not differ between treatment groups.
      Peripheral and central systolic BP, and heart rate (HR), were 11.2 mm Hg
      (P=0.03), 9.5 mm Hg (P=0.04) and 7 beats per minute (P=0.02) higher,
      respectively, with amphetamine, compared with control. A nonsignificant reduction
      in myocardial perfusion (BUI) was seen with amphetamine. Other cardiac and
      cerebral haemodynamics were unaffected. Amphetamine did not improve motor
      impairment or function after ischaemic stroke but did significantly increase BP
      and HR without altering cerebral haemodynamics.

PMID- 17443209
TI  - Effect of moderate weight reduction on resting and exercise blood pressure in
      overweight subjects.

PMID- 17443210
TI  - Measurements of insulin resistance in hypertension: where are we now?

PMID- 17443211
TI  - Validity and reproducibility of HOMA-IR, 1/HOMA-IR, QUICKI and McAuley's indices
      in patients with hypertension and type II diabetes.
AB  - The aim of this study was to evaluate the validity and reliability of homeostasis
      model assessment-insulin resistance (HOMA-IR) index, its reciprocal (1/HOMA-IR),
      quantitative insulin sensitivity check index (QUICKI) and McAuley's index in
      hypertensive diabetic patients. In 78 patients with hypertension and type II
      diabetes glucose, insulin and triglyceride levels were determined after a 12-h
      fast to calculate these indices, and insulin sensitivity (IS) was measured with
      the hyperinsulinemic euglycemic clamp technique. Two weeks later, subjects had
      again their glucose, insulin and triglycerides measured. Simple and multiple
      linear regression analysis were applied to assess the validity of these indices
      compared to clamp IS and coefficients of variation between the two visits were
      estimated to assess their reproducibility. HOMA-IR index was strongly and
      inversely correlated with the basic IS clamp index, the M-value (r=-0.572,
      P<0.001), M-value normalized with subjects' body weight or fat-free mass and
      every other clamp-derived index. 1/HOMA-IR and QUICKI indices were positively
      correlated with the M-value (r=0.342, P<0.05 and r=0.456, P<0.01, respectively)
      and the rest clamp indices. McAuley's index generally presented less strong
      correlations (r=0.317, P<0.05 with M-value). In multivariate analysis, HOMA-IR
      was the best fit of clamp-derived IS. Coefficients of variation between the two
      visits were 23.5% for HOMA-IR, 19.2% for 1/HOMA-IR, 7.8% for QUICKI and 15.1% for
      McAuley's index. In conclusion, HOMA-IR, 1/HOMA-IR and QUICKI are valid estimates
      of clamp-derived IS in patients with hypertension and type II diabetes, whereas
      the validity of McAuley's index needs further evaluation. QUICKI displayed better
      reproducibility than the other indices.

PMID- 17443212
TI  - Validity of four indirect methods to measure adherence in primary care
      hypertensives.
AB  - High blood pressure (HBP) is one of the most important risk factors for morbidity
      and mortality in the world. Non-adherence to medication is associated with the
      lack of control of HBP. The objective of this study was to assess the validity of
      four indirect methods for measuring adherence to medication to control HBP in
      primary health care. A random sample of 120 hypertensive patients who were
      undergoing treatment for at least 2 months in a primary care unit in
      Florianopolis (Brazil) were included in the study. The independent variables were
      four indirect methods to measure adherence to medication: knowledge regarding the
      HBP medication, the blood pressure level, attitude regarding the medication
      intake (Morisky-Green test) and self-reported adherence. The classification of
      HBP was based on criteria established by the Brazilian Ministry of Health. The
      gold standard used for measuring adherence was the pill count. Logistic
      regression was used to estimate sensitivity (highest value of 88.2% for self
      report), specificity (highest value of 70.7% for HBP control), positive
      predictive value (highest value of 46.4% for HBP control) and negative predictive
      value (highest value of 79.1% for Morisky-Green test) for each of the indirect
      methods. No indirect method of measuring adherence had a good positive predictive
      value for adherence, which was best predicted by patients' age and whether they
      managed to control HBP. The results also revealed low treatment adherence (31.2%)
      and low control of HBP (37.6%). Non-adherence was mainly associated with side
      effects of the treatment.

PMID- 17443213
TI  - Selection of patients for ambulatory monitoring in a primary care setting.

PMID- 17443214
TI  - Gene transfer to interfere with TNFalpha signaling in neuropathic pain.
AB  - We examined the role of spinal tumor necrosis factor-alpha (TNFalpha) in
      neuropathic pain of peripheral nerve origin. Two weeks after selective L5 spinal
      nerve ligation (SNL), rats exhibiting mechanical allodynia and thermal
      hyperalgesia showed a marked increase in full-length membrane-associated TNFalpha
      (mTNFalpha) in the dorsal horn of spinal cord, in the absence of detectable
      soluble TNFalpha peptide. Local release of the soluble p55 TNF receptor, achieved
      by herpes simplex virus vector-based gene transfer to dorsal root ganglion,
      resulted in a reduction of mTNFalpha and concomitant reductions in interleukin
      1beta and phosphorylated p38 MAP kinase. Subcutaneous inoculation of soluble p55
      TNF receptor expressing HSV vector into the plantar surface of the hind foot
      ipsilateral to the ligation 1 week before SNL delayed the development of both
      mechanical allodynia and thermal hyperalgesia; subcutaneous inoculation into the
      hind foot ipsilateral to the ligation 1 week after SNL resulted in a
      statistically significant reduction in mechanical allodynia and thermal
      hyperalgesia that was apparent 1 week after inoculation. These results suggest a
      novel 'reverse signaling' through glial mTNFalpha, which may be exploited to
      downregulate the neuroimmune reaction in spinal cord to reduce chronic
      neuropathic pain.

PMID- 17443215
TI  - Strategies for CNS-directed gene delivery: in vivo gene transfer to the brain
      using SV40-derived vectors.
AB  - Gene transfer to the central nervous system (CNS) has been approached using
      various vectors. Recombinant SV40-derived vectors (rSV40s) transduce neurons and
      microglia effectively in vitro, so we tested rSV40s gene transfer to the CNS in
      vivo, and characterized the distribution, duration and cell types transduced. We
      used rSV40s carrying Human Immunodeficiency Virus Type 1 Net protein (HIV-1 Nef)
      with a C-terminal FLAG epitope tag as a marker, and another with Cu/Zn superoxide
      dismutase (SOD1). Rats were given vectors stereotaxically, either
      intraparenchymally into the caudate-putamen (CP) or into the lateral ventricle
      (LV). FLAG expression was studied for 3 months by immunostaining serial brain
      sections. After intraparenchymal administration, numerous transgene-expressing
      cells were seen, many as far as 4 mm from the injection site. Transgene
      expression remained strong throughout the 3-month study period. Coimmunostaining
      for lineage markers showed that neurons and, more rarely, microglial cells were
      tranduced, except astrocytes and oligodendroglia. After injection into the LV,
      high levels of transgene expression were detected throughout the frontal cortex
      by Western analysis. Systemic mannitol-induced hyperosmolarity further augmented
      LV transgene delivery. SV40-derived vectors may, thus, be useful for long-term
      gene expression in the brain, whether locally by intraparenchymal administration
      or diffusely by intraventricular injection, with or without mannitol.

PMID- 17443216
TI  - Synergy of adoptive T-cell therapy and intratumoral suicide gene therapy is
      mediated by host NK cells.
AB  - In situ tumor cell killing by the herpes simplex virus thymidine kinase (HSVtk)
      gene can effectively prime antitumor T-cell responses, at least in part through
      local induction of a pro-inflammatory environment. Therefore, we reasoned that
      tumor-associated HSVtk expression would significantly enhance the efficacy of
      adoptive T-cell transfer (ACT) of (tumor) antigen-specific T cells into tumor
      bearing hosts. When B16ovaHSVtk tumors were treated with ganciclovir (GCV), along
      with suboptimal numbers of activated OT-1T cells, complete tumor regressions were
      observed where GCV, or ACT, alone was completely ineffective. To our surprise,
      analysis of regressing tumors showed no increases in intratumoral OT-1T cell
      trafficking. However, the intratumoral percentages of both OT-1 and endogenous
      natural killer (NK) cells were substantially increased over controls. Depletion
      of endogenous NK cells abrogated the efficacy of the combination therapy and
      reduced the percentages of interferon-gamma(IFNgamma)-secreting OT-1T cells in
      mice that received combined therapy to levels similar to those of control mice.
      These data suggest that even relatively low levels of gene transfer of suicide
      genes into tumors may have therapeutic value as an adjuvant for other T-cell
      therapies, by providing immunological signals that support T-cell activation and
      expansion in vivo.

PMID- 17443219
TI  - Prognostic analysis of aberrant somatic hypermutation of RhoH gene in diffuse
      large B cell lymphoma.

PMID- 17443220
TI  - JAK2V617F as progression marker in CMPD and as cooperative mutation in AML with
      trisomy 8 and t(8;21): a comparative study on 1103 CMPD and 269 AML cases.

PMID- 17443222
TI  - Efficacy and safety of low-dose alemtuzumab as treatment of autoimmune hemolytic
      anemia in pretreated B-cell chronic lymphocytic leukemia.

PMID- 17443223
TI  - Recurrent chromosomal aberration at 12q15 in chronic idiopathic myelofibrosis
      with or without JAK2(V617F) mutation.

PMID- 17443224
TI  - Cytoplasmic mutated nucleophosmin (NPM) defines the molecular status of a
      significant fraction of myeloid sarcomas.

PMID- 17443225
TI  - Development of adult T-cell leukemia in donor-derived human T-cell leukemia virus
      type I-infected T cells after allogeneic bone marrow transplantation.

PMID- 17443226
TI  - Janus kinase mutations in the development of acute megakaryoblastic leukemia in
      children with and without Down's syndrome.

PMID- 17443227
TI  - High-resolution genomic profiling of childhood ALL reveals novel recurrent
      genetic lesions affecting pathways involved in lymphocyte differentiation and
      cell cycle progression.
AB  - Gross cytogenetic anomalies are traditionally being used as diagnostic,
      prognostic and therapeutic markers in the clinical management of cancer,
      including childhood acute lymphoblastic leukemia (ALL). Recently, it has become
      increasingly clear that genetic lesions driving tumorigenesis frequently occur at
      the submicroscopic level and, consequently, escape standard cytogenetic
      observations. Therefore, we profiled the genomes of 40 childhood ALLs at high
      resolution. We detected multiple de novo genetic lesions, including gross
      aneuploidies and segmental gains and losses, some of which were subtle and
      affected single genes. Many of these lesions involved recurrent (partially)
      overlapping deletions and duplications, containing various established leukemia
      associated genes, such as ETV6, RUNX1 and MLL. Importantly, the most frequently
      affected genes were those controlling G1/S cell cycle progression (e.g. CDKN2A,
      CDKN1B and RB1), followed by genes associated with B-cell development. The latter
      group includes microdeletions of the B-lineage transcription factors PAX5, EBF,
      E2-2 and IKZF1 (Ikaros), as well as genes with other established roles in B-cell
      development, that is RAG1 and RAG2, FYN, PBEF1 or CBP/PAG. The fact that we
      frequently encountered multiple lesions affecting genes involved in cell cycle
      regulation and B-cell differentiation strongly suggests that both these processes
      need to be targeted independently and simultaneously to trigger ALL development.

PMID- 17443228
TI  - Signal transduction pathways that contribute to myeloid differentiation.
AB  - The production of mature, differentiated myeloid cells is regulated by the action
      of hematopoietic cytokines on progenitor cells in the bone marrow. Cytokines
      drive the process of myeloid differentiation by binding to specific cell-surface
      receptors in a stage- and lineage-specific manner. Following the binding of a
      cytokine to its cognate receptor, intracellular signal-transduction pathways
      become activated that facilitate the myeloid differentiation process. These
      intracellular signaling pathways may promote myelopoiesis by stimulating
      expansion of a progenitor pool, supporting cellular survival during the
      differentiation process, or by directly driving the phenotypic changes associated
      with differentiation. Ultimately, pathways that drive the differentiation process
      converge on myeloid transcription factors, including PU.1 and the C/EBP family,
      that are critical for differentiation to proceed. While much is known about the
      cytokines, cytokine receptors and transcription factors that regulate myeloid
      differentiation, less is known about the precise roles that specific signaling
      mediators play in promoting myeloid differentiation. Recently, however, the
      application of novel pharmacologic inhibitors, siRNA strategies, and transgenic
      and knockout models has begun to shed light on the involvement and function of
      signaling pathways in normal myeloid differentiation. This review will discuss
      the roles that key signaling pathways and mediators play in myeloid
      differentiation.

PMID- 17443229
TI  - Common genetic variation in the gene encoding interleukin-1-receptor antagonist
      (IL-1RA) is associated with altered circulating IL-1RA levels.
AB  - Interleukin-1-receptor antagonist (IL-1RA) modulates the biological activity of
      the proinflammatory cytokine interleukin-1 (IL-1) and could play an important
      role in the pathophysiology of inflammatory and metabolic traits. We genotyped
      seven single nucleotide polymorphisms (SNPs) that capture a large proportion of
      common genetic variation in the IL-1RN gene in 1256 participants from the
      Invecchiare in Chianti study. We identified five SNPs associated with circulating
      IL-1RA levels with varying degrees of significance (P-value range=0.016-4.9 x 10(
      5)). We showed that this association is likely to be driven by one haplotype,
      most strongly tagged by rs4251961. This variant is only in weak linkage
      disequilibrium (r(2)=0.25) with a previously reported variable number of tandem
      repeats polymorphism (VNTR) in intron-2 although a second variant, rs579543, that
      tags the VNTR (r(2)=0.91), may also be independently associated with IL-1RA
      levels (P=0.03). We found suggestive evidence that the C allele at rs4251961 that
      lowers IL-1RA levels is associated with an increased IL-1beta (P=0.03) level and
      may also be associated with interferon -gamma (P=0.03), alpha-2 macroglobulin
      (P=0.008) and adiponectin (P=0.007) serum levels. In conclusion, common variation
      across the IL-1RN gene is strongly associated with IL-1RA levels.

PMID- 17443232
TI  - Review of the NSW Public Health Bulletin: a qualitative survey of stakeholders.
AB  - In 2005, the NSW Department of Health commissioned an external review of the NSW
      Public Health Bulletin. This article describes the methods and findings of the
      qualitative survey. Participants included people working in population health
      from within the Department of Health, area health services, the tertiary sector
      and non-government organisations. There were fifty interviews, two focus groups
      and eight written surveys. The review found substantial support and respect for
      the Bulletin. It described the features of the Bulletin that stakeholders valued
      and provided suggestions to strengthen the publication. These findings will guide
      developments in the Bulletin's purpose, presentation, content and distribution
      for its readership.

PMID- 17443233
TI  - Results from the 2000 fax-back survey to readers about the NSW Public Health
      Bulletin.
AB  - Publications must regularly reflect on their performance to ensure that they
      remain relevant to their readership and are fulfilling their objectives. In 2000
      the 'NSW Public Health Bulletin Discussion Paper 2000'was released, with
      recommendations regarding all aspects of the Bulletin content, distribution and
      editorial management. A copy was sent to 1200 people with a fax-back survey
      seeking general feedback on the Bulletin and the recommendations. There was a
      response rate of 11 per cent. The survey identified broad support for the
      Bulletin and the recommendations. Findings included strong support for
      encouraging electronic access but maintaining the distribution of the printed
      copy. Subsequent changes to production of the Bulletin have included expanding
      the number of reviewers of articles and making improvements to the website.

PMID- 17443234
TI  - Bug Breakfast in the Bulletin: epidemic keratoconjunctivitis: an outbreak in New
      South Wales.

PMID- 17443235
TI  - Communicable diseases report, New South Wales, for September and October 2006.

PMID- 17443236
TI  - A web log analysis of the online NSW Public Health Bulletin for 2001-2003.
AB  - The web logs of the online version of the NSW Public Health Bulletin were
      analysed to understand the patterns of use. Twenty-nine months of data, for the
      period January 2001 to May 2003, were extracted from archived files stored by the
      NSW Department of Health. HTML and PDF hits were included; other types of hits,
      for example image hits, were not. Five potentially useful variables were
      identified: Internet protocol address; date of access; time of access; document
      accessed; and means of access. There were 384,887 hits during the period,
      approximately 442 per day. The rate of hits per month increased from 8288 in 2001
      to 21,288 in 2003. The PDF version was used more than the HTML version.
      Examination of HTML hits revealed how different parts of the Bulletin were being
      used. This information provides evidence to inform planning.

PMID- 17443237
TI  - When and how can endpoints be changed after initiation of a randomized clinical
      trial?

PMID- 17443238
TI  - Mapping the literature of health care management.
AB  - OBJECTIVES: The research provides an overview of the health care management
      literature and the indexing coverage of core journal literature. METHOD:
      Citations from five source journals for the years 2002 through 2004 were studied
      using the protocols of the Mapping the Literature of Allied Health Project and
      Mapping the Literature of Nursing Project. The productivity of cited journals was
      analyzed by applying Bradford's Law of Scattering. RESULTS: Journals were the
      most frequently cited format, followed by books. Only 3.2% of the cited journal
      titles from all 5 source journals generated two-thirds of the cited titles. When
      only the health care management practitioner-oriented source journals were
      considered, two-thirds of the output of cited journal titles came from 10.8% of
      the titles. Science Citation Index and PubMed provided the best overall coverage
      of the titles cited by all 5 source journals, while the cited titles from the 2
      practitioner-oriented journals were covered most completely by Social Sciences
      Citation Index and Business Source Complete. CONCLUSIONS: Health care management
      is a multidisciplinary field. Librarians must consider the needs of their users
      and assist them by providing the necessary materials and combination of indexes
      to access this field adequately.

PMID- 17443239
TI  - The pipeline problem: where do we go from here?

PMID- 17443240
TI  - Response to Glanville et al.: How to identify randomized controlled trials in
      MEDLINE: ten years on.

PMID- 17443241
TI  - Response to Glanville et al.

PMID- 17443243
TI  - Response to Perryman.

PMID- 17443244
TI  - Using the literature to evaluate diagnostic tests: amylase or lipase for
      diagnosing acute pancreatitis?

PMID- 17443245
TI  - Clinical, classroom, or personal education: attitudes about health literacy.
AB  - PURPOSE: This study explores how diverse attitudes about health literacy are
      assessed by medical librarians and other health care professionals. PROCEDURES:
      An online survey of thirty-six items was conducted using Q methodology in two
      phases in spring 2005 and winter 2006. Respondents (n = 51) were nonrandomly self
      selected from a convenience sample of members of the Medical Library Association
      and a group of environmental health consultants to the National Library of
      Medicine. FINDINGS: Three factors were identified. Factor 1 is optimistic and
      supportive of health literacy's transformative sociocultural and professional
      potential, if clinical settings become a launching point for health literacy
      activities. Factor 2 is less optimistic about health literacy's potential to
      improve clinical or patient outcomes and prefers to focus health literacy
      initiatives on classroom education settings. Factor 3 supports improving the
      nation's health literacy but tends to support health literacy initiatives when
      people privately interact with health information materials. CONCLUSIONS: Each
      factor's attitudes about the appropriate educational venue to initiate health
      literacy activities are different and somewhat mutually exclusive. This suggests
      that health literacy is seen through different perceptual frameworks that
      represent a possible source of professional disagreement.

PMID- 17443246
TI  - How primary care physicians' attitudes toward risk and uncertainty affect their
      use of electronic information resources.
AB  - OBJECTIVE: The research sought to determine if primary care physicians' attitudes
      toward risk taking or uncertainty affected how they sought information and used
      electronic information resources when answering simulated clinical questions.
      METHODS: Using physician-supplied data collected from existing risk and
      uncertainty scales, twenty-five physicians were classified as risk seekers (e.g.,
      enjoying adventure), risk neutral, or risk avoiders (e.g., cautious) and stressed
      or unstressed by uncertainty. The physicians then answered twenty-three multiple
      choice, clinically focused questions and selected two to pursue further using
      their own information resources. Think-aloud protocols were used to collect
      searching process and outcome data (e.g., searching time, correctness of answers,
      searching techniques). RESULTS: No differences in searching outcomes were
      observed between the groups. Physicians who were risk avoiding and those who
      reported stress when faced with uncertainty each showed differences in searching
      processes (e.g., actively analyzing retrieval, using searching heuristics or
      rules). Physicians who were risk avoiding tended to use resources that provided
      answers and summaries, such as Cochrane or UpToDate, less than risk-seekers did.
      Physicians who reported stress when faced with uncertainty showed a trend toward
      less frequent use of MEDLINE, when compared with physicians who were not stressed
      by uncertainty. CONCLUSIONS: Physicians' attitudes towards risk taking and
      uncertainty were associated with different searching processes but not outcomes.
      Awareness of differences in physician attitudes may be key in successful design
      and implementation of clinical information resources.

PMID- 17443247
TI  - Realizing what's essential: a case study on integrating electronic journal
      management into a print-centric technical services department.
AB  - OBJECTIVE: To support migration from print to electronic resources, the
      Cushing/Whitney Medical Library at Yale University reorganized its Technical
      Services Department to focus on managing electronic resources. METHODS: The
      library hired consultants to help plan the changes and to present recommendations
      for integrating electronic resource management into every position. The library
      task force decided to focus initial efforts on the periodical collection. To free
      staff time to devote to electronic journals, most of the print subscriptions were
      switched to online only and new workflows were developed for e-journals. RESULTS:
      Staff learned new responsibilities such as activating e-journals, maintaining
      accurate holdings information in the online public access catalog and e-journals
      database ("electronic shelf reading"), updating the link resolver knowledgebase,
      and troubleshooting. All of the serials team members now spend significant
      amounts of time managing e-journals. CONCLUSIONS: The serials staff now spends
      its time managing the materials most important to the library's clientele (e
      journals and databases). The team's proactive approach to maintenance work and
      rapid response to reported problems should improve patrons' experiences using e
      journals. The library is taking advantage of new technologies such as an
      electronic resource management system, and library workflows and procedures will
      continue to evolve as technology changes.

PMID- 17443248
TI  - Using the Turning Research Into Practice (TRIP) database: how do clinicians
      really search?
AB  - OBJECTIVES: Clinicians and patients are increasingly accessing information
      through Internet searches. This study aimed to examine clinicians' current search
      behavior when using the Turning Research Into Practice (TRIP) database to examine
      search engine use and the ways it might be improved. METHODS: A Web log analysis
      was undertaken of the TRIP database-a meta-search engine covering 150 health
      resources including MEDLINE, The Cochrane Library, and a variety of guidelines.
      The connectors for terms used in searches were studied, and observations were
      made of 9 users' search behavior when working with the TRIP database. RESULTS: Of
      620,735 searches, most used a single term, and 12% (n = 75,947) used a Boolean
      operator: 11% (n = 69,006) used "AND" and 0.8% (n = 4,941) used "OR." Of the
      elements of a well-structured clinical question (population, intervention,
      comparator, and outcome), the population was most commonly used, while fewer
      searches included the intervention. Comparator and outcome were rarely used.
      Participants in the observational study were interested in learning how to
      formulate better searches. CONCLUSIONS: Web log analysis showed most searches
      used a single term and no Boolean operators. Observational study revealed users
      were interested in conducting efficient searches but did not always know how.
      Therefore, either better training or better search interfaces are required to
      assist users and enable more effective searching.

PMID- 17443249
TI  - Information-seeking behavior of women in their path to an innovative alternate
      treatment for symptomatic uterine fibroids.
AB  - OBJECTIVES: The purpose of the study was to discover how women found out about
      uterine fibroid embolization (UFE) for the treatment of symptomatic uterine
      fibroids. METHODS: The study retrospectively tracked women from the beginning of
      their illnesses and analyzed their information-seeking behaviors. Twenty-eight
      women who had the procedure at the Detroit Medical Center were interviewed using
      a standard script. Median values and frequencies were calculated to represent
      information needs, information sources, and perceived helpfulness. Spearman
      correlations were calculated to find relationships between demographics and
      information needs. RESULTS: Although the women expressed a great need for almost
      all types of information (median = 5), those with higher levels of education
      indicated a greater need to know the reasons that their doctors had for
      suggesting treatments (r = 0.55). The gathered frequencies indicated that
      friends, magazines, television, and the Internet were important information
      sources. A preliminary model of information seeking showed that while friends,
      magazines, and television made several of the women aware of the new procedure,
      the Internet was heavily utilized for learning about treatment options.
      CONCLUSIONS: Health sciences librarians may inform women about their health and
      treatment options by guiding women to easily readable, authoritative, and
      reliable information sources, including Web information sites.

PMID- 17443250
TI  - Conducting a user-centered information needs assessment: the Via Christi
      Libraries' experience.
AB  - PURPOSE: The research sought to provide evidence to support the development of a
      long-term strategy for the Via Christi Regional Medical Center Libraries.
      METHODS: An information needs assessment was conducted in a large medical center
      serving approximately 5,900 physicians, clinicians, and nonclinical staff in 4
      sites in 1 Midwestern city. Quantitative and qualitative data from 1,295 self
      reporting surveys, 75 telephone interviews, and 2 focus groups were collected and
      analyzed to address 2 questions: how could the libraries best serve their
      patrons, given realistic limitations on time, resources, and personnel, and how
      could the libraries best help their institution improve patient care and
      outcomes? RESULTS: Clinicians emphasized the need for "just in time" information
      accessible at the point of care. Library nonusers emphasized the need to market
      library services and resources. Both clinical and nonclinical respondents
      emphasized the need for information services customized to their professional
      information needs, preferences, and patterns of use. Specific information needs
      in the organization were identified. DISCUSSION/CONCLUSIONS: The results of this
      three-part, user-centered information needs assessment were used to develop an
      evidence-based strategic plan. The findings confirmed the importance of promoting
      library services in the organization and suggested expanded, collaborative roles
      for hospital librarians.

PMID- 17443251
TI  - An assessment of the information-seeking abilities and needs of practicing speech
      language pathologists.
AB  - OBJECTIVES: This study assessed the information-seeking practices and needs of
      speech-language pathologists (SLPs). Improved understanding of these needs can
      inform librarians and educators to better prepare students in principles and
      methods of evidence-based practice (EBP) and, through continuing education (CE),
      promote the integration of EBP into clinical practice of SLPs. METHODS: A 16
      question survey was mailed to 1,000 certified speech-language pathologists in the
      United States. RESULTS: Two hundred and eight usable surveys were returned for a
      response rate of 21%. For clinical questions, SLPs most often consulted with a
      colleague, participated in CE activities, and searched the open Internet. Few
      respondents relied on scholarly journal articles for assistance with clinical
      cases. The most prominent barriers to finding appropriate information were time
      and knowledge of where and how to find relevant information. Few reported having
      information literacy instruction by a librarian. DISCUSSION: If EBP is to become
      a viable practice in clinical decision making, there appears to be a tremendous
      need for information literacy instruction in the university curriculum, as well
      as through CE activities for currently practicing SLPs. Given respondents'
      reported lack of time and limited access to full-text journals containing
      evidence relevant to clinical practice, the field of speech-language pathology
      will need to generate readily accessible clinical summaries of research evidence
      through meta-analyses, systematic reviews, and clinical practice guidelines.

PMID- 17443252
TI  - Interlibrary loan in US and Canadian health sciences libraries 2005: update on
      journal article use.
AB  - PURPOSE: The authors analyzed 2.48 million interlibrary loan (ILL) requests
      entered in the National Library of Medicine's (NLM's) DOCLINE system from 3,234
      US and Canadian medical libraries during fiscal year (FY) 2005 to study their
      distribution and nature and the journals in which requested articles were
      published. METHODS: Data from DOCLINE and NLM's indexing system and online
      catalog were used to analyze all DOCLINE ILL transactions acted on from October
      2004 to September 2005. The authors compared results from this analysis to
      previous data collected in FY 1992. RESULTS: Overall ILL volume in the United
      States and Canada is at about the same level as FY 1992 despite marked growth in
      online searching, knowledge discovery tools, and journals available online. Over
      21,000 unique journal titles and 1.4 million unique articles were used to fill
      2.2 million ILL requests in FY 2005. Over 1 million of the articles were
      requested only once by any network library. Fifty-two percent (11,022) of
      journals had 5 or fewer requests for articles from all the years of a journal by
      all libraries in the network. Fifty-two percent of the articles requested were
      published within the most recent 5 years. CONCLUSION: The overall ILL profile in
      the libraries studied has changed little since FY 1992, notable given other
      changes in publishing. Small changes, however, may reveal developing trends.
      Total ILL traffic has been declining in recent years following a peak in 2002,
      and fewer of the articles requested were published in the most recent five years
      compared to requests from 1992.

PMID- 17443253
TI  - Mapping the literature of athletic training.
AB  - PURPOSE: This paper identifies the core literature of athletic training and
      determines which major databases provide the most thorough intellectual access to
      this literature. METHODS: This study collected all cited references from 2002 to
      2004 of three journals widely read by those in the athletic training field.
      Bradford's Law of Scattering was applied to the resulting list to determine the
      core journal titles in the discipline. Three major databases were reviewed for
      extent of their coverage of these core journals. RESULTS: Of the total 8,678
      citations, one-third referenced a compact group of 6 journals; another third of
      the citations referenced an additional 40 titles. The remaining 2,837 citations
      were scattered across 1,034 additional journal titles. CONCLUSIONS: The number
      and scatter of citations over a three-year period identified forty-six key
      journals in athletic training. The study results can inform athletic trainers of
      the core literature in their field, encourage database producers (e.g., MEDLINE,
      SPORTDiscus, CINAHL) to increase coverage of titles that are not indexed or
      underindexed, and guide purchasing decisions for libraries serving athletic
      training programs.

PMID- 17443254
TI  - Expert searching in consumer health: an important role for librarians in the age
      of the Internet and the Web.
AB  - OBJECTIVES: The Patient Education Resource Center at the University of Michigan
      Comprehensive Cancer Center conducts mediated searches for patients and families
      seeking information on complex medical issues, state-of-the-art treatments, and
      rare cancers. The current study examined user satisfaction and the impact of
      information provided to this user population. METHODS: This paper presents the
      results of 566 user evaluation forms collected between July 2000 and June 2006
      (1,532 forms distributed; 37% response rate). Users provided both quantitative
      and qualitative feedback, which was analyzed and classified into recurrent
      themes. RESULTS: The majority of users reported they were very satisfied with the
      information provided (n = 472, 83%). Over half of users (n = 335, 60%) shared or
      planned to share the information with their health care provider, and 51% (n =
      286) reported that the information made an impact on treatment or quality of
      life. For 96.2% of users (n = 545), some or all of the information provided had
      not been received through any other source. DISCUSSION: The results demonstrate
      that, despite the end-user driven Internet, patients and families are not able to
      find all the information they need on their own. Expert searching remains an
      important role for librarians working with consumer health information seekers.

PMID- 17443255
TI  - Chemistry and biological activities of CO-releasing molecules (CORMs) and
      transition metal complexes.
AB  - The advent of CO as a small molecule that, in addition to NO, elicits essential
      biological functions has initiated the search for compounds and complexes capable
      of releasing CO in a well defined manner under physiological conditions. Since
      some pharmacological and therapeutic effects of CO have been established in
      preclinical studies, tailor-made CO-releasing molecules (CORMs) which could be
      utilized as pharmaceuticals could be of great benefit for many patients. Release
      of CO(2) is one of the most common features in chemistry and NO producing
      molecules are very well established but compounds with CO-releasing properties
      are rare. Some of the more promising candidates and molecules under study are
      discussed in this article. Furthermore, molecules that possess intrinsic features
      to serve as potential CO-RMs and merit in depth investigations are proposed. The
      focus is thereby on main group compounds and on transition element complexes. It
      should be emphasized that CORMs not only have encouraging prospects as
      therapeutic agents but may also be significant for synthetic pathways to novel
      complexes containing the CO ligand. To underline the prospects of CORMs, the
      chemical part is embedded in a biological and medicinal context.

PMID- 17443256
TI  - A new one-dimensional Mn(II) complex containing two enantiomeric subunits with
      mixed carboxylate, pyridine and sulfinate bridges.
AB  - The first O,O'-bonded metal-stabilized sulfinate has been isolated and
      structurally characterized to show a novel one-dimensional chain structure
      containing both the enantiomers of the subunit Mn(2-sinic)(DMSO)2.

PMID- 17443257
TI  - Sulfimidation--a new and versatile strategy for the post ring-closure
      derivatisation of mixed thia/oxa crowns.
AB  - Reaction of [18]aneO(5)S with the aminating agent MSH results in the
      {[18]aneO(5)SNH(2)}+ cation which may be converted through to the linked crown
      system [({[18]aneO(5)S}(2)N)]+ via deprotonation, bromination and reaction with
      the parent crown; significantly, despite their positive charge, both systems can
      coordinate sodium cations to the ether linkages.

PMID- 17443258
TI  - "Water-stable boron-iodinated dicarbollide dianions [7,8-nido-C2H2B9I9]2- and
      [7,8-nido-C2H2B9I8H]2-".
AB  - The reaction of 3,4,5,7,8,9,10,11,12-I(9)-1,2-closo-C(2)B(10)H(3) with KOH/EtOH
      gave a mixture of the boron periodinated [1,2,3,4,5,6,9,10,11-I(9)-7,8-nido
      C(2)B(9)H(2)](2-) and the highly iodinated on boron [1,2,4,5,6,9,10,11-I(8)-7,8
      nido-C(2)B(9)H(3)](2-) in approximately 50% each. Moreover,
      3,4,5,6,7,8,9,10,11,12-I(10)-1,2-closo-C(2)B(10)H(2) was reacted with KOH/EtOH to
      purely produce [1,2,3,4,5,6,9,10,11-I(9)-7,8-nido-C(2)B(9)H(2)](2-). It is the
      first dinegative dicarbollide stable in water or protic solvent reported in
      literature.

PMID- 17443259
TI  - Synthesis and characterisation of zirconium-amido guanidinato complex: a
      potential precursor for ZrO2 thin films.
AB  - A new zirconium complex, bis-(ethylmethylamido)-bis-(N,N'-diisopropyl-2
      ethylmethylamidoguanidinato)-zirconium(iv)
      {[(N(i)Pr)(2)C(NEtMe)](2)Zr(NEtMe)(2)}, was synthesised by partial replacement of
      amide ligands with bidentate guanidinate ligands. The monomeric Zr complex was
      characterised by (1)H-NMR, (13)C-NMR, EI-MS, elemental analysis, and single
      crystal X-ray diffraction studies. The thermal properties of the compound was
      studied by thermogravimetric and differential thermal analysis (TG/DTA). The new
      Zr compound is thermally stable and can be sublimed quantitatively which renders
      it promising for thin film growth using vapor deposition techniques like chemical
      vapor deposition (CVD) and atomic layer deposition (ALD). The use of this complex
      for CVD of ZrO(2) on Si(100) substrates was attempted in combination with oxygen
      as the oxidant. Stoichiometric ZrO(2) films with preferred orientation at lower
      growth temperatures was obtained and the films were almost carbon free. The
      preliminary electrical characterisation of ZrO(2) films showed encouraging
      results for possible applications in dielectric oxide structures.

PMID- 17443260
TI  - Bis(acetylacetonato)ruthenium(II) complexes containing alkynyldiphenylphosphines.
      Formation and redox behaviour of [Ru(acac)2(Ph2PC triple bond CR)2] (R=H, Me, Ph)
      complexes and the binuclear complex cis-[{Ru(acac)2}2(micro-Ph2PC triple bond
      CPPh2)}2].
AB  - Two equivalents of Ph(2)PC triple bond CR (R=H, Me, Ph) react with thf solutions
      of cis-[Ru(acac)(2)(eta(2)-alkene)(2)] (acac=acetylacetonato; alkene=C(2)H(4), 1;
      C(8)H(14), 2) at room temperature to yield the orange, air-stable compounds trans
      [Ru(acac)(2)(Ph(2)PC triple bond CR)(2)] (R=H, trans-3; Me=trans-4; Ph, trans-5)
      in isolated yields of 60-98%. In refluxing chlorobenzene, trans-4 and trans-5 are
      converted into the yellow, air-stable compounds cis-[Ru(acac)(2)(Ph(2)PC triple
      bond CR)(2)] (R=Me, cis-4; Ph, cis-5), isolated in yields of ca. 65%. From the
      reaction of two equivalents of Ph(2)PC triple bond CPPh(2) with a thf solution of
      2 an almost insoluble orange solid is formed, which is believed to be trans
      [Ru(acac)(2)(micro-Ph(2)PC triple bond CPPh(2))](n) (trans-6). In refluxing
      chlorobenzene, the latter forms the air-stable, yellow, binuclear compound cis
      [{Ru(acac)(2)(micro-Ph(2)PC triple bond CPPh(2))}(2)] (cis-6). Electrochemical
      studies indicate that cis-4 and cis-5 are harder to oxidise by ca. 300 mV than
      the corresponding trans-isomers and harder to oxidise by 80-120 mV than cis
      [Ru(acac)(2)L(2)] (L=PPh(3), PPh(2)Me). Electrochemical studies of cis-6 show two
      reversible Ru(II/III) oxidation processes separated by 300 mV, the estimated
      comproportionation constant (K(c)) for the equilibrium cis-6(2+) + cis6 <=> 2(cis
      6(+)) being ca. 10(5). However, UV-Vis spectra of cis-6(+) and cis-6(2+),
      generated electrochemically at -50 degrees C, indicate that cis-6(+) is a Robin
      Day Class II mixed-valence system. Addition of one equivalent of AgPF(6) to trans
      3 and trans-4 forms the green air-stable complexes trans-3 x PF(6) and trans-4 x
      PF(6), respectively, almost quantitatively. The structures of trans-4, cis-4,
      trans-4 x PF(6) and cis-6 have been confirmed by X-ray crystallography.

PMID- 17443261
TI  - Molecular structures of free quinuclidine and its adducts with metal trihydrides,
      MH3 (M=B, Al or Ga), studied by gas-phase electron diffraction, X-ray diffraction
      and quantum chemical calculations.
AB  - The structure of quinuclidine, HC(CH(2)CH(2))(3)N, has been re-investigated by
      quantum chemical calculations and by gas-phase electron diffraction (GED). The
      GED data, together with published rotational constants, have been analysed using
      the SARACEN method to determine the most reliable structure (r(h1)) for the
      gaseous molecule. The structures of two adducts of quinuclidine with group 13
      trihydride molecules, MH(3) (M=B, Al), have also been determined by GED and
      quantum chemical calculations. The effect of the coordination of these hydrides
      to the quinuclidine nitrogen atom has been investigated, and the structural
      changes and energetics of adduct formation are discussed. We also present the
      crystal structure of quinuclidine borane.

PMID- 17443262
TI  - Organoplatinum complexes containing bis(diphenylphosphino)amine as ligand:
      uncommon case of N-H . . . I-Pt hydrogen bonding.
AB  - The complex [PtMe(2)(dppa)], 1a, dppa = Ph(2)PNHPPh(2), which has previously been
      prepared as a mixture with the dimeric form [Pt(2)Me(4)(micro-dppa)(2)], was
      synthesized in pure form by the reaction of [PtCl(2)(dppa)] with MeLi. The aryl
      analogue [Pt(p-MeC(6)H(4))(2)(dppa)], 1b, was prepared by replacement of SMe(2)
      in cis-[Pt(p-MeC(6)H(4))(2)(SMe(2))(2)] with dppa. The reaction of the chelate
      complexes 1 with one equiv. of dppa afforded the complexes [PtR(2)(dppa-P)(2)],
      R=Me, 2a and R=p-MeC(6)H(4) 2b. The reaction of [PtR(2)(dppa)], 1, with neat MeI
      gave the organoplatinum(iv) complexes [PtR(2)MeI(dppa)], R=Me, 5a and R=p
      MeC(6)H(4), 5b. The structure of 5a, determined by X-ray crystallography,
      indicated that the complex undergoes self-assembly by intermolecular N-H . . . I
      Pt hydrogen bonding. MeI was also double oxidatively added to
      organodiplatinum(ii) complex cis,cis-[Me(2)Pt(micro-SMe(2))(micro-dppa)PtMe(2)],
      to give diorganoplatinum(iv) complex [Me(3)Pt(micro-dppa)(micro-I)(2)PtMe(3)], 4.
      The aryl analogue organodiplatinum(ii) complex cis,cis-[(p-MeC(6)H(4))(2)Pt(micro
      SMe(2))(micro-dppa)Pt(p-MeC(6)H(4))(2)], 3b, was prepared by the reaction of cis
      [Pt(p-MeC(6)H(4))(2)(SMe(2))(2)] with half equiv. of dppa, but 3b refused to
      react with MeI, probably because of the steric effects of the aryl ligands. The
      tetramethyl complex [PtMe(4)(dppa)], 6, was prepared either by reaction of 5a
      with MeLi or by replacement of SMe(2) in [Pt(2)Me(8)(micro-SMe(2))(2)] with dppa.
      All the complexes were fully characterized in solution by multinuclear NMR ((1)H,
      (13)C, (31)P and (195)Pt) methods and their coordination compared with that of
      the corresponding known dppm complexes.

PMID- 17443263
TI  - Synthesis, characterization, electrochemical and photophysical properties of
      elbow-shaped trinuclear Ru(II) complexes, building blocks for novel
      supramolecular constructions.
AB  - Three trinuclear elbow-shaped Ru(II) complexes based on the non symmetrical
      bridging PHEHAT ligand (PHEHAT = 1,10-phenanthrolino[5,6-b]-1,4,5,8,9,12
      hexaazatriphenylene) have been prepared and characterized by NMR,
      electrochemistry, absorption and emission spectroscopy. It is shown that the
      dichloro trinuclear complex 1 should behave as an excellent precursor for the
      synthesis of larger species. Indeed, it reacts easily with 1,10-phenanthroline
      (phen) and 1,4,5,8-tetraazaphenanthrene (TAP) and leads to the trinuclear
      compounds 2 and 3, respectively. The electrochemical and emission studies
      indicate that for 2 and 3, there is an intramolecular energy transfer from the
      center to the periphery of the elbow-shaped trinuclear complex, whereas for
      complex 1 the energy transfer takes place in the other direction.

PMID- 17443264
TI  - Intercalation of Re(phen)(CO)3Cl into zirconium phosphate: a water insoluble
      inorganic complex immobilized in a highly polar rigid matrix.
AB  - The intercalation of fac-tricarbonylchloro-1,10-phenanthrolinerhenium(i)
      (Re(phen)(CO)(3)Cl) within zirconium phosphate (ZrP) has been achieved using a
      hydrated ZrP phase that possesses six water molecules per formula unit. This
      intercalation occurs only at high solution molar ratios (Re : ZrP, 3 : 1) and is
      characterized by the emergence of a new phase in the X-ray powder diffraction
      (XRPD) pattern with an interlayer distance of 15.6 A. The XRPD patterns show a
      decrease in the crystallinity upon intercalation of the inorganic complex. The
      MLCT absorption bands of Re(phen)(CO)(3)Cl-containing ZrP materials are red
      shifted in comparison with the complex in acetonitrile whilst the luminescence
      spectra at different loading levels are blue shifted up to 30 nm in comparison
      with the complex in acetonitrile. This blue shift is consistent with the
      rigidochromic effect. The luminescence lifetime of Re(phen)(CO)(3)Cl within ZrP
      was increased in comparison with its lifetime in acetonitrile solution but is
      shorter than that of Re(phen)(CO)(3)Cl in frozen glass and polyesther resins. To
      our knowledge, this is the first example of a water insoluble metal complex
      intercalated within the layers of ZrP, which opens up new possibilities in the
      intercalation chemistry of this lamellar material and in the study of host-guest
      interactions.

PMID- 17443265
TI  - Neutral (bis-beta-diketonato) iron(III), cobalt(II), nickel(II), copper(II) and
      zinc(II) metallocycles: structural, electrochemical and solvent extraction
      studies.
AB  - Neutral dimeric metallocyclic complexes of type [M(2)(L(1))(2)B(n)] (where M =
      cobalt(II), nickel(II) and zinc(II), L(1) is the doubly deprotonated form of a
      1,3-aryl linked bis-beta-diketone ligand of type 1,3-bis(RC(O)CH(2)C(O))C(6)H(4)
      (R=Me, n-Pr, t-Bu) and B is pyridine (Py) or 4-ethylpyridine (EtPy)) have been
      synthesised, adding to similar complexes already reported for copper(II). New
      lipophilic ligand derivatives with R = octyl or nonyl were also prepared for use
      in solvent extraction experiments. Structural, electrochemical and solvent
      extraction investigations of selected metal complex systems from the above series
      are reported, with the X-ray structures of [Co(2)(L(1))(2)(Py)(4)] x 2.25CHCl(3)
      x 0.5H(2)O (R=Pr), [Co(2)(L(1))(2)(EtPy)(4)] (R=t-Bu), [Ni(2)(L(1))(2)(EtPy)(4)]
      (R=t-Bu), [Zn(2)(L(1))(2)(EtPy)(2)] (R=Me) and [Zn(2)(L(1))(2)(EtPy)(4)] (R=t-Bu)
      being presented. The electrochemistry of H(2)L(1) (R=t-Bu) and of
      [Fe(2)(L(1))(3)], [Co(2)(L(1))(2)(Py)(4)], [Ni(2)(L(1))(2)(Py)(4)],
      [Cu(2)(L(1))(2)] and [Zn(2)(L(1))(2)(Py)(2)] has been examined. Oxidative
      processes for the complexes are dominantly irreversible, but several examples of
      quasireversible behaviour were observed and support the assignment of an anodic
      process, seen between +1.0 and +1.6 V, as a metal-centred oxidation. The
      reduction processes for the respective metal complexes are not simple, and
      irreversible in most cases. Solvent extraction studies (water/chloroform)
      involving variable concentrations of metal, bis-beta-diketone and heterocyclic
      base have been performed for cobalt(II) and zinc(II) using a radiotracer
      technique to probe the stoichiometries of the extracted species in each case.
      Synergism was observed when 4-ethylpyridine was added to the bis-beta-diketone
      ligand in the chloroform phase. Competitive extraction studies show a clear
      uptake preference for copper(II) over cobalt(II), nickel(II), zinc(II) and
      cadmium(II).

PMID- 17443266
TI  - Vitamin D and BMC.

PMID- 17443267
TI  - Polyamine analogues - an update.
AB  - The polyamines are growth factors in both normal and cancer cells. As the
      intracellular polyamine content correlates positively with the growth potential
      of that cell, the idea that depletion of polyamine content will result in
      inhibition of cell growth and, particularly tumour cell growth, has been
      developed over the last 15 years. The polyamine pathway is therefore a target for
      development of rationally designed, antiproliferative agents. Following the
      lessons from the single enzyme inhibitors (alpha-difluoromethylornithine DFMO),
      three generations of polyamine analogues have been synthesised and tested in
      vitro and in vivo. The analogues are multi-site inhibitors affecting multiple
      reactions in the pathway and thus prevent the up-regulation of compensatory
      reactions that have been the downfall of DFMO in anticancer chemotherapy.
      Although the initial concept was that the analogues may provide novel anticancer
      drugs, it now seems likely that the analogues will have wider applications in
      diseases involving hyperplasia.

PMID- 17443268
TI  - Regulation of ornithine decarboxylase during oncogenic transformation: mechanisms
      and therapeutic potential.
AB  - The activity of ornithine decarboxylase (ODC(1)), the first enzyme in polyamine
      biosynthesis, is induced during carcinogenesis by a variety of oncogenic stimuli.
      Intracellular levels of ODC and the polyamines are tightly controlled during
      normal cell growth, and regulation occurs at the levels of transcription,
      translation and protein degradation. Several known proto-oncogenic pathways
      appear to control ODC transcription and translation, and dysregulation of
      pathways downstream of ras and myc result in the constitutive elevation of ODC
      activity that occurs with oncogenesis. Inhibition of ODC activity reverts the
      transformation of cells in vitro and reduces tumor growth in several animal
      models, suggesting high levels of ODC are necessary for the maintenance of the
      transformed phenotype. The ODC irreversible inactivator DFMO has proven to be not
      only a valuable tool in the study of ODC in cancer, but also shows promise as a
      chemopreventive and chemotherapeutic agent in certain types of malignancies.

PMID- 17443269
TI  - Kidney growth, hypertrophy and the unifying mechanism of diabetic complications.
AB  - Michael Brownlee has proposed a 'Unifying Mechanism' of hyperglycemia-induced
      damage in diabetes mellitus. At the crux of this hypothesis is the generation of
      reactive oxygen species (ROS), and their impact on glycolytic pathways. Diabetes
      is the leading cause of chronic kidney failure. In the early phase of diabetes,
      prior to establishment of proteinuria or fibrosis, comes kidney growth and
      hyperfiltration. This early growth phase consists of an early period of
      hyperplasia followed by hypertrophy. Hypertrophy also contributes to cellular
      oxidative stress, and may precede the ROS perturbation of glycolytic pathways
      described in the Brownlee proposal. This increase in growth promotes
      hyperfiltration, and along with the hypertrophic phenotype appears required for
      hyperglycemia-induced cell damage and the progression of downstream diabetic
      complications. Here we will evaluate this growth phenomenon in the context of
      diabetes mellitus.

PMID- 17443271
TI  - Molecular analysis of hearing loss associated with enlarged vestibular aqueduct
      in the mainland Chinese: a unique SLC26A4 mutation spectrum.
AB  - It has been shown that mutations in the SLC26A4 gene are involved in syndromic
      deafness characterized by congenital sensorineural hearing impairment and goitre
      (Pendred's syndrome), as well as in congenital isolated deafness (DFNB4), both of
      which are associated with enlarged vestibular aqueduct (EVA). The prevalence of
      SLC26A4 mutations in Pendred's syndrome is clearly established in many ethnic
      groups, but the data from Mainland Chinese patients with deafness and EVA remain
      poor. In this report, 15 patients from 13 unrelated Chinese families with
      deafness and EVA were analyzed for SLC26A4 using direct sequencing. A total of 15
      pathogenic mutations were observed in 11 unrelated families, 4 of which were
      novel. One mutation, IVS7-2A>G, was most common, accounting for 22.3% (5/22) of
      all the mutant alleles, and H723R was infrequent. To date, a total of 23
      mutations have been reported among the Chinese, 13 of which were unique. In
      conclusion, EVA could be a radiological marker for SLC26A4 analysis among
      Mainland Chinese hearing-loss patients, and the SLC26A4 mutation spectrum in the
      Chinese was different from other reported populations.

PMID- 17443270
TI  - Hernia repair with porcine small-intestinal submucosa.
AB  - PURPOSE: Although at present nonabsorbable meshes are the preferred material for
      tension-free hernioplasty, some problems with their use have yet to be addressed
      (i.e., chronic pain and infections). In order to address these disadvantages, a
      collagen-based material, the porcine small-intestinal submucosa mesh (Surgisis
      Inguinal Hernia Matrix, Cook Surgical, Bloomington, IN, USA), has recently been
      developed for hernia repair. METHODS: With the aim of investigating the clinical
      safety and effectiveness of Surgisis IHM inguinal hernia repair, we report our
      experience of 45 consecutive hernioplasties with a medium-term follow-up. The
      surgical technique for the use of this material in hernioplasty is described in
      detail. RESULTS: Although some local (i.e., seromas) and general (i.e.,
      hyperpyrexia), complications appeared in the immediate postoperative period (all
      of them disappeared spontaneously), no rejection or infection was observed after
      operations. At the 2-year follow-up, a low degree of pain and discomfort and no
      recurrences were observed. CONCLUSIONS: We conclude that the Surgisis IHM
      hernioplasty is feasible with promising results and, from a clinical perspective,
      seems safe and effective.

PMID- 17443274
TI  - Percutaneous MR-guided cryoablation for malignancies, with a focus on renal cell
      carcinoma.
AB  - Cryosurgery is the oldest thermal ablation method, and was first performed in the
      mid-nineteenth century. Since the development of cryosurgical systems capable of
      delivering liquid nitrogen, organs in various regions have been treated with
      cryosurgery. However, the lack of an adequate monitoring modality during the
      freezing process did not allow the precise and complete destruction of lesions
      deep inside the parenchyma. This led to local recurrences caused by
      unsatisfactory results of treatment. Recently, a magnetic resonance (MR)
      compatible argon-based cryoablation system has been developed, and a combination
      of this cryoablation system and MR imaging has been shown to be an effective
      method for treating malignant tumors. In this article, we describe our clinical
      experience of percutaneous MR-guided cryoablation for malignancies, focusing on
      renal cell carcinoma.

PMID- 17443273
TI  - CT-guided radiofrequency ablation for lung cancer.
AB  - Recently, percutaneous radiofrequency (RF) ablation has been increasingly
      performed as a local treatment for lung malignancies. In RF ablation, the
      application of radiofrequency agitates ions in the tissues surrounding the
      electrode, causing them to fluctuate at high speed, and this generates frictional
      heat. The generated heat coagulates the tissues. Puncture is carried out under
      computed tomography (CT) guidance in the same manner as that for needle biopsy.
      In animal studies, it was speculated that air functioned as an insulator and that
      the heat did not damage normal surrounding lung parenchyma to any great extent,
      because lung is filled with air. An experimental VX2 tumor in rabbits was well
      controlled by RF ablation. Since the clinical use of RF ablation for lung
      malignancies was first reported in 2000, many series have been published. The
      patients reported in these studies were not candidates for surgical treatment,
      either because of poor cardiopulmonary function and comorbidities, or because
      they refused surgery. With RF ablation, complete necrosis can be expected for
      tumors with a diameter of 3 cm or less. Palliative RF ablation may be indicated
      for large tumors. The most frequent complication associated with puncture was
      pneumothorax, with a frequency higher for RF ablation compared with that for
      needle biopsy. The initial results have been promising, but we await future
      reports for long-term results.

PMID- 17443275
TI  - MR-guided microwave ablation for malignancies.
AB  - Since we first successfully performed magnetic resonance (MR)-guided microwave
      coagulation therapy for liver tumors in January 2000, we have developed new MR
      compatible instruments, laparoscopy and thoracoscopy, which have enabled us to
      approach liver tumors located just below the diaphragm and in contact with other
      organs. We have customized software for an MR gradient-based tracking system for
      the easy detection of the location and orientation of treatment area and for the
      real-time display of MR temperature maps with a scale bar. Navigation software
      was customized to enable real-time image navigation. The reformatted images in
      the two perpendicular planes complemented the limitations of real-time MR
      imaging. Evaluation software, "FootPrint," was useful for distinguishing treated
      areas from untreated areas and improved the evaluation of treatment accuracy.
      These newly developed MR-guided systems that utilize microwave have played
      important roles in more accurate, safer, and easier treatment for liver tumors.
      We have treated 184 patients using these new techniques without major
      complications.

PMID- 17443276
TI  - MRI-guided laparoscopic and robotic surgery for malignancies.
AB  - Endoscopic surgery has some clear benefits, but it also has some disadvantages in
      reducing surgeons' normal dexterity and limiting their ability to deal with
      difficult situations. Computer-aided surgery has been proposed to overcome some
      of the drawbacks of traditional minimally invasive surgery. The proposed systems
      make possible a secure, precise procedure with no limitations on the operator's
      freedom of movement. Image-guided surgery is a new technical tool in surgical
      oncology. Interventional magnetic resonance imaging (MRI) has entered a new stage
      in which computer-based techniques play an expanding role in planning,
      monitoring, and controlling procedures. MRI-guided surgery not only represents a
      technical challenge but is a transformation from conventional hand-eye
      coordination to interactive navigational operations. We have recently developed
      an MRI-guided robot-assisted interventional surgical system as well as an MRI
      compatible endoscope. They allow the performance of precise image-guided
      interventional therapy and endoscopic surgery. MRI-guided laparoscopic surgery is
      now feasible for malignancies and will play an important part in the development
      of minimally invasive therapy.

PMID- 17443277
TI  - Combination of radiotherapy with EGFR antagonists for head and neck carcinoma.
AB  - The introduction of biologically sound radiation fractionation regimens and
      combinations of radiotherapy with chemotherapy have gradually improved both the
      survival of patients with locally advanced head and neck squamous cell carcinoma
      (HNSCC) and the prospect of organ preservation. Long-term follow-up, however, has
      shown that some of the radiation-chemotherapy combinations are associated with
      increased late toxicity. This observation, in conjunction with advances in tumor
      biology, has led to the launch of investigations into molecular markers and
      targets for therapeutic interventions. Research on the epidermal growth factor
      receptor (EGFR)-mediated signaling pathway has enriched our understanding of the
      biology of HNSCC, in terms of carcinogenesis and cellular processes governing
      tumor response to therapy. The finding that the addition of an antibody-based
      inhibitor of the EGFR pathway to radiotherapy significantly improves locoregional
      control and overall survival rates in patients with locally advanced HNSCC,
      without increasing radiation-induced toxicity, has resulted in the growing
      acceptance of such combined regimens as a frontline therapy option for locally
      advanced HNSCC. Because such therapy has benefited only an additional 10%-15% of
      patients, studies are being undertaken to identify markers and mechanisms of
      resistance to EGFR antagonists that are essential for the further refinement of
      therapy. Overall, preclinical and clinical studies on EGFR have validated the
      concept that selective tumor radiation sensitization can be achieved by
      modulating a specific perturbed signaling pathway, and these studies have
      increased the enthusiasm for developing and investigating other novel agents
      targeting other cellular processes.

PMID- 17443278
TI  - Role of thymidine phosphorylase and orotate phosphoribosyltransferase mRNA
      expression and its ratio to dihydropyrimidine dehydrogenase in the prognosis and
      clinicopathological features of patients with pancreatic cancer.
AB  - BACKGROUND: Thymidine phosphorylase (TP), orotate phosphoribosyltransferase
      (OPRT), and dihydropyrimidine dehydrogenase (DPD) are important enzymes related
      to the metabolism of 5-fluorouracil and its derivatives. In this study, we
      analyzed the expression of these enzymes and evaluated the association between
      the expression of these enzymes and clinicopathological features and prognosis in
      patients with pancreatic cancer. METHODS: TP, OPRT, and DPD mRNA expressions were
      detected using a real-time reverse transcriptional-polymerase chain reaction
      method or by immunohistochemistry, using surgical specimens obtained from 25
      patients with pancreatic cancer. RESULTS: TP mRNA expression was lower in cases
      with an alpha infiltration growth pattern than in cases with other infiltration
      growth patterns (P < 0.05). OPRT mRNA expression was higher in poorly
      differentiated-type cases than in differentiated type cases (P < 0.05). TP-, OPRT
      , and DPD-positive stainings were found in 15 of 24 cases (63%), 10 of 19 cases
      (53%), and 14 of 21 cases (67%), respectively. There were significant
      correlations or trends between the mRNA and protein expressions of TP, OPRT, and
      DPD. Patients with a low TP/DPD ratio survived significantly longer than those
      with a high ratio (P < 0.05). Multivariate analysis demonstrated a significantly
      poorer outcome in patients with a high TP/DPD ratio compared with in patients
      with a low ratio (P < 0.05). CONCLUSION: The TP/DPD ratio might be useful as a
      prognostic factor in patients with pancreatic cancer.

PMID- 17443279
TI  - Decrease of creatinine clearance rate with aging in patients with head and neck
      cancer in Japan.
AB  - BACKGROUND: We aimed to clarify the reason for the lower dosage of cis-platinum
      (CDDP) in patients with head and neck cancer in Japan compared with that in other
      countries, by evaluating renal function. METHODS: We studied 375 patients with
      head and neck cancer who had been hospitalized from January 1998 to October 2005,
      to evaluate and treat the disease. The creatinine clearance rate (Ccr) was
      calculated at least three times before beginning the treatments, and the average
      Ccr was estimated to evaluate the renal function. RESULTS: The Ccr decreased with
      aging, and the percentages of patients with Ccr lower than 65 ml/min per 1.73
      m(2) were 27.1% of patients in their fifties, 36.8% in their sixties, 62.3% in
      their seventies, and 87.5% in their eighties. There was no correlation between
      renal function and the Japanese lifestyle (i.e., diet. water consumption).
      CONCLUSION: The renal function of Japanese decreases rapidly with aging, whereas
      that of Americans is maintained for longer periods. The poor renal function of
      Japanese is one of the causes of the need to reduce the dosage of or avoid the
      administration of CDDP in cancer patients.

PMID- 17443280
TI  - Collagen gel matrix assay as an in vitro chemosensitivity test for malignant
      astrocytic tumors.
AB  - BACKGROUND: The efficacy of individual chemotherapy based on chemosensitivity has
      scarcely been studied. METHODS: We examined the chemosensitivites for four
      anticancer agents - 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3 (2-chloroethyl)-3
      nitrosourea hydrochloride (ACNU), carboplatin, cisplatin, and etoposide - of 43
      malignant astrocytic tumors (21 anaplastic astrocytomas and 22 glioblastomas) by
      using a collagen gel matrix assay, and we also determined the survival periods of
      the tumor-bearing patients. The chemosensitivity was evaluated in terms of the
      growth inhibition rate, using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl
      tetrazolium bromide (MTT) method. RESULTS: For the anaplastic astrocytomas, the
      mean growth inhibitory rate was 33.2% with cisplatin, 37.2% with carboplatin,
      28.0% with ACNU, and 24.8% with etoposide. For the glioblastomas, these rates
      were 36.9%, 42.3%, 23.2%, and 34.8%, respectively. The median overall and
      progression-free survivals of anaplastic astrocytoma-bearing patients who had
      undergone chemotherapy with two anticancer drugs, both of which showed
      significant anticancer activity (growth inhibitory rate >30%) were significantly
      longer than those of the patients who had been treated with two drugs, one or
      both of which did not show significant anticancer activity. On the other hand,
      there was no significant difference in the overall or the progression-free
      survivals in the two corresponding groups of glioblastoma-bearing patients.
      CONCLUSION: The collagen gel matrix assay is clinically useful to determine in
      vitro chemosensitivity that reflects in vivo chemosensitivity. Individual
      chemotherapy for malignant astrocytic tumors, based on chemosensitivity data,
      could contribute to longer survival, particularly in anaplastic astrocytoma
      bearing patients.

PMID- 17443281
TI  - Lymphatic invasion is a prognostic factor for bladder cancer treated with radical
      cystectomy.
AB  - BACKGROUND: We aimed to elucidate the significance of pathological prognostic
      factors in patients with bladder cancer treated with radical cystectomy and
      pelvic lymphadenectomy focusing on the association between lymphatic invasion and
      disease recurrence. METHODS: Ninety-one patients with ladder cancer who had
      undergone radical cystectomy were examined retrospectively. Clinicopathological
      findings and clinical outcomes were analyzed. Patients who received palliative
      cystectomy or neoadjuvant chemotherapy and patients who did not receive
      lymphadenectomy owing to a poor general condition or far advanced local disease
      status were excluded. RESULTS: Lymphatic invasion and lymph node involvement were
      present in 45.1% and 23.1% of patients, respectively. Multivariate analyses,
      using the Cox proportional hazards model, indicated that lymphatic invasion
      (hazard ratio [HR], 5.30; P = 0.007) and lymph node involvement (HR = 3.05; P =
      0.016) were independent prognostic factors for disease-specific survival. Of the
      91 patients, 29 (31.9%) had recurrent disease during the follow-up period. The
      rate of recurrence in patients with lymphatic invasion and without lymph node
      involvement was 50% (11/22), which was not significantly different from that in
      patients with both lymphatic invasion and lymph node involvement (73.7%; 14/19; P
      = 0.121), indicating a high risk of disease recurrence in patients with bladder
      cancer with lymphatic invasion even in the absence of the lymph node involvement.
      CONCLUSION: In patients with bladder cancer treated with radical cystectomy,
      lymphatic invasion is an independent prognostic factor for disease-specific and
      disease-free survival. Patients with lymphatic invasion have a high risk of
      disease recurrence after radical cystectomy even in the absence of lymph node
      involvement.

PMID- 17443282
TI  - A review of 331 rhabdomyosarcoma cases in patients treated between 1991 and 2002
      in Japan.
AB  - BACKGROUND: To prepare for a Japanese nationwide group study of patients with
      rhabdomyosarcoma (RMS), we examined the characteristics and outcomes of RMS
      patients treated recently in Japan. METHODS: We classified 331 RMS patients
      treated between 1991 and 2002 at 63 institutions according to the Intergroup
      Rhabdomyosarcoma Study V (IRS-V) risk-group classification. RESULTS: Ten-year
      survival rates were 86.3% for patients in low-risk subgroup A, 80.7% for low-risk
      subgroup B, 62.7% for intermediate-risk subgroup A, 61.7% for intermediate-risk
      subgroup B, and 38.1% for the high-risk group. The outcomes of the patients in
      the former three groups were 8%, 12%, and 21% worse than the outcomes of the
      respective patients in the IRS-III and early IRS-IV data. The frequency of the
      alveolar histological subtype was 21.8%. Chimera genes, which are useful markers
      for the alveolar subtype, had been examined in only 10% of the patients treated
      in the period of this investigation. The survival rates of our patients with
      embryonal and alveolar histological subtypes (65.9% and 63.4%, respectively) were
      not significantly different. Among the patients in the high-risk group, the 5
      year survival of patients who received high-dose chemotherapy (HDC; 58.2%) was
      significantly better than that of patients who did not receive HDC (18.4%).
      CONCLUSION: Patients in the lower-risk groups with embryonal-type tumors had
      poorer outcomes in this retrospective study. The better outcome of patients in
      the high-risk group is apparently due to the outstanding results obtained with an
      HDC regimen in a single institution. These results suggest that there is a need
      for: (1) a standard therapy, (2) a rapid central pathology review including a
      chimera gene analysis for the lower-risk group, and (3) evaluation of the
      efficacy of the high-dose regimen for the high-risk group in Japan.

PMID- 17443283
TI  - Doxifluridine combined with weekly paclitaxel for second-line treatment in
      patients with gastric cancer resistant to TS-1.
AB  - BACKGROUND: Many patients with gastric cancer respond to TS-1, but some fail to
      respond or have recurrence. Second-line therapy is needed. METHODS: We performed
      a pilot study in patients with advanced gastric cancer who did not respond to TS
      1 or who had disease recurrence. The patients received oral doxifluridine (600
      mg/day) on days 1 to 21 and an intravenous infusion of paclitaxel (70 mg/m(2)) on
      days 7, 14, and 21 of a 28-day cycle. The treatment was repeated until disease
      progression or prohibitive toxicity. Response rate, duration of response, median
      survival time (MST), effects on pleural effusion, ascites, and other signs, and
      toxicity were evaluated. RESULTS: The study group comprised 52 patients. The
      response rate was 28%. The duration of response was 103 days. The MST after the
      start of second-line treatment was 175 days (95% confidence interval, 135 to 224
      days). Pleural effusion or ascites resolved or decreased in 73% of the patients.
      Hair loss occurred in 32 patients (62%), and leukopenia developed in 28 (54%,
      grade 3 in 1 patient and grade 2 or lower in the others). The MST after the start
      of treatment with TS-1 was about 16 months. CONCLUSION: A combination of
      doxifluridine and weekly paclitaxel is expected to be an effective second-line
      treatment for gastric cancer not responding to TS-1, especially in patients with
      malignant ascites or pleural effusion. However, it remains unclear whether
      paclitaxel plus doxifluridine results in a better response and survival benefit
      than paclitaxel alone in this subgroup of patients. Further studies are therefore
      necessary.

PMID- 17443284
TI  - Successful treatment of multiple hepatocellular carcinoma with tumor thrombi in
      the major portal branches by intraarterial 5-fluorouracil perfusion chemotherapy
      combined with subcutaneous interferon-alpha and hepatectomy.
AB  - We experienced a patient who received successful treatment for multiple
      hepatocellular carcinoma (HCC) nodules, with tumor thrombi in the major portal
      branches, with intraarterial 5-fluorouracil perfusion chemotherapy combined with
      subcutaneous interferon-alpha administration. The patient was a 50-year-old man
      with hepatitis C virus and HCC. The tumors consisted of a 5-cm main nodule in the
      right lobe (segment 8) and multiple intrahepatic metastases. The tumor also
      involved portal vein thrombosis throughout the right portal branch. After two
      cycles of interferon-alpha/5-fluorouracil combination chemotherapy, tumor markers
      demonstrated a decreasing tendency. Nine months after the initiation of this
      therapy, the tumors were limited to the right lobe and were surgically removed by
      S8 subsegmentectomy, S5 partial hepatectomy, and portal thrombectomy. The serum
      levels of both alpha-fetoprotein and protein induced by vitamin K absence II fell
      to normal levels after hepatic resection. Fifty-eight months after the first
      treatment, he is alive with several recurrent nodules in the liver. In
      conclusion, the interferon-alpha/5-fluorouracil combination therapy is a useful
      treatment for HCC in patients who have multiple intrahepatic metastases and
      portal vein thrombosis. In addition to this therapy, combined modality therapy
      including, for example, surgical resection, can sometimes have a dramatic
      therapeutic effect, shown by tumor markers reverting to normal levels.

PMID- 17443285
TI  - Paraneoplastic vasculitis of central nervous system presenting as recurrent
      cryptogenic stroke.
AB  - We report the case of paraneoplastic vasculitis of the central nervous system
      associated with breast cancer. A 54-year old woman had a complete workup because
      of recidive seizures. Magnetic resonance imaging (MRI) showed cerebral and
      medullary cryptogenic lesions, and a diagnosis of encephalomyelitis of unknown
      origin was made. She was treated with corticosteroids, but because of cognitive
      impairment and recurrence of epileptic seizures, she was finally transferred to
      our Neurology Department. The previous diagnosis was then changed, because a
      poorly differentiated invasive lobular breast cancer was discovered. Thoracic and
      abdominal computed tomography (CT) scans diagnosed pulmonary, pericardial,
      adrenal, and renal metastases. Because MRI findings did not fit with the
      diagnosis of brain metastases, a CT-guided cerebral biopsy was performed, and she
      was eventually diagnosed with paraneoplastic vasculitis of the central nervous
      system.

PMID- 17443286
TI  - Malignant paraganglioma arising from the kidney.
AB  - Paragangliomas are rare neoplasms arising from undifferentiated cells of the
      primitive neural crest. We report a case of a 34-year-old patient with renal
      paraganglioma. Complete surgical resection of the tumor was performed without
      intraoperative incident. The diagnosis was made based on immunohistochemical and
      ultramicroscopic analyses. The postoperative course was uneventful. Based on the
      obtained results, we discuss the clinical aspects of the case and the diagnosis.

PMID- 17443287
TI  - Report on the Fifth African League Against Rheumatism Congress in Nairobi, Kenya.

PMID- 17443288
TI  - Congenital diffuse anaplastic astrocytoma with ependymal and leptomeningeal
      spread: case report.

PMID- 17443289
TI  - Pleiotrophin expression in astrocytic and oligodendroglial tumors and it's
      correlation with histological diagnosis, microvascular density, cellular
      proliferation and overall survival.
AB  - BACKGROUND: Pleiotrophin (PTN) is a secreted cytokine with several properties
      related with tumor development, including differentiation, angiogenesis,
      invasion, apoptosis and metastasis. There is evidence that PTN has also a
      relevant role in primary brain neoplasms and its inactivation could be important
      to treatment response. Astrocytic and oligodendroglial tumors are the most
      frequent primary brain neoplasms. Astrocytic tumors are classified as pilocytic
      astrocytoma (PA), diffuse astrocytoma (DA), anaplastic astrocytoma (AA) and
      glioblastoma (GBM). Oligodendroglial tumors are classified as oligodendroglioma
      (O) and anaplastic oligodendroglioma (AO). The aim of the present study was to
      compare PTN expression, in astrocytomas and oligodendrogliomas and its
      association with the histological diagnosis, microvascular density, proliferate
      potential and clinical outcome. METHODS: Seventy-eight central nervous system
      tumors were analyzed. The histological diagnosis in accordance with WHO
      classification was: 13PA, 18DA, 8AA, 15GBM, 16O and 8AO. Immunohistochemistry was
      realized with these specific antibodies: pleiotrophin, CD31 to microvascular
      density and Ki-67 to cell proliferation. RESULTS: PTN expression was
      significantly higher in GBM and AA when compared to PA and higher in GBM compared
      to DA. PTN expression did not differ between O and AO. Proliferate index and
      microvascular density were evaluated only in high grade tumors (AA, GBM and AO)
      divided in three groups according to PTN expression (low, intermediate and high).
      These results showed no statistical difference between PTN expression and index
      of cellular proliferation and neither to PTN expression and microvascular
      density. Overall survival (OS) analysis (months) showed similar results in high
      grade gliomas with different levels of PTN expression. CONCLUSIONS: Our results
      suggest that PTN expression is associated with histopathological grade of
      astrocytomas. Proliferation rate, microvascular density and overall survival do
      not seem to be associated with PTN expression.

PMID- 17443290
TI  - Ferumoxtran-10 enhancement in orthotopic xenograft models of human brain tumors:
      an indirect marker of tumor proliferation?
AB  - PURPOSE: Ferumoxtran-10 belongs to the Ultra Small Particles of Iron Oxide
      (USPIO) class of contrast agents and induces delayed tumor enhancement in brain
      tumors, reflecting the trapping of iron oxide particles by the macrophages and
      activated microglia. The aim of the study was to compare Ferumoxtran-10 contrast
      enhancement in four human high-grade glioma xenograft models (TCG2, TCG3, TCG4,
      and U87) with different growing profiles. MATERIALS AND METHODS: Fragments of
      human malignant glioma were orthotopically xenografted into the brain of four
      groups of nude mice. All mice underwent a MRI examination 24 h after intravenous
      administration of Ferumoxtran-10 (axial T1 SE weighted MR images). The contrast
      enhancement observed in the different tumor types was measured and was correlated
      to in vivo tumor growth and to histological parameters, such as proliferative
      tumor cell fraction, apoptosis, vascular density, and Perls' staining score.
      RESULTS: A good relationship was observed: (a) between tumor-to-background
      contrast and proliferative index, (b) between tumor-to-background contrast and
      tumor growth, and (c) between tumor-to-background contrast and Perls' staining
      score. The registered MR enhancement contrasts were not influenced by apoptotic
      index and by vascular density in these experimental xenografts. CONCLUSIONS:
      Tumor contrast enhancement 24 h after intravenous Ferumoxtran-10 administration
      seems to be well correlated to tumor proliferative index and tumor growth and
      could be used as an indirect marker of tumor proliferation.

PMID- 17443291
TI  - The changes of heavy metal and metallothionein distribution in testis induced by
      cadmium exposure.
AB  - Cadmium (Cd) is known to cause various disorders in the testis, and
      metallothionein (MT) is known as a protein, which has a detoxification function
      for heavy metals. However, the changes of Fe, Cu, and Zn distribution in the
      testis induced by Cd exposure have not been well examined. Moreover, only a few
      studies have been reported on the localization of MT after Cd exposure. In this
      study, we have investigated the changes of Fe, Cu, and Zn distribution in Cd
      exposed testis by a newly developed in air micro-Particle Induced X-ray Emission
      (PIXE) method. Also, we examined the distribution of MT expression in testis. In
      the testis of Cd-treated rats with significant increases of lipid peroxidation,
      the sertoli cell tight junction was damaged by Cd exposure, resulting from
      disintegration of the blood testis barrier (BTB). Evaluation by in air micro-PIXE
      method revealed that Cd and Fe distribution were increased in the interstitial
      tissues and seminiferous tubules. The histological findings indicated that the
      testicular tissue damage was advanced, which may have been caused by Fe flowing
      into seminiferous tubules followed by disintegration of the BTB. As a result, Fe
      was considered to enhance the tissue damage caused by Cd exposure. MT was
      detected in spermatogonia, spermatocytes, and Sertoli's cells in the testis of Cd
      treated rats, but was not detected in interstitial tissues. These results
      suggested that MT was induced by Cd in spermatogonia, spermatocytes, and
      Sertoli's cells, and was involved in the resistance to tissue damage induced by
      Cd.

PMID- 17443292
TI  - Genome-wide identification and expression analysis of rice cell cycle genes.
AB  - Cyclins, cyclin-dependent kinases, and a number of other proteins control the
      progression of plant cell cycle. Although extensive studies have revealed the
      roles of some cell cycle regulators and the underlying mechanisms in Arabidopsis,
      relatively a small number of cell cycle regulators were functionally analyzed in
      rice. In this study, we describe 41 regulators in the rice genome. Our results
      indicate that the rice genome contains a less number of the core cell cycle
      regulators than the Arabidopsis one does, although the rice genome is much larger
      than the Arabidopsis one. Eight groups of CDKs similar to those in Arabidopsis
      were identified in the rice genome through phylogenetic analysis, and the
      corresponding members in the different groups include E2F, CKI, Rb, CKS and Wee.
      The structures of the core cell regulators were relatively conserved between the
      rice and Arabidopsis genomes. Furthermore, the expression of the majority of the
      core cell cycle genes was spatially regulated, and the most closely related ones
      showed very similar patterns of expression, suggesting functional redundancy and
      conservation between the highly similar core cell cycle genes in rice and
      Arabidopsis. Following auxin or cytokinin treatment, the expression of the core
      cell cycle genes was either upregulated or downregulated, suggesting that auxin
      and/or cytokinin may directly regulate the expression of the core cell cycle
      genes. Our results provide basic information to understand the mechanism of cell
      cycle regulation and the functions of the rice cell cycle genes.

PMID- 17443293
TI  - Congruence between morphological and molecular markers inferred from the analysis
      of the intra-morphotype genetic diversity and the spatial structure of Oxalis
      tuberosa Mol.
AB  - Oxalis tuberosa is an important crop cultivated in the highest Andean zones. A
      germplasm collection is maintained ex situ by CIP, which has developed a
      morphological markers system to classify the accessions into morphotypes, i.e.
      groups of morphologically identical accessions. However, their genetic uniformity
      is currently unknown. The ISSR technique was used in two experiments to determine
      the relationships between both morphological and molecular markers systems. The
      intra-morphotype genetic diversity, the spatial structures of the diversity and
      the congruence between both markers systems were determined. In the first
      experience, 44 accessions representing five morphotypes, clearly distinct from
      each other, were analyzed. At the molecular level, the accessions exactly
      clustered according to their morphotypes. However, a genetic variability was
      observed inside each morphotype. In the second experiment, 34 accessions
      gradually differing from each other on morphological base were analyzed. The
      morphological clustering showed no geographical structure. On the opposite, the
      molecular analysis showed that the genetic structure was slightly related to the
      collection site. The correlation between both markers systems was weak but
      significant. The lack of perfect congruence between morphological and molecular
      data suggests that the morphological system may be useful for the morphotypes
      management but is not appropriate to study the genetic structure of the oca. The
      spatial structure of the genetic diversity can be related to the evolution of the
      species and the discordance between the morphological and molecular structures
      may result from similar selection pressures at different places leading to
      similar forms with a different genetic background.

PMID- 17443294
TI  - [HIV: prevention and education].

PMID- 17443295
TI  - [Epidemiology of HIV infections in Germany].
AB  - The course of the HIV epidemic in Germany can be modelled by back calculation
      until the beginning of the nineties. The recent course of the epidemic can only
      be derived from surveillance data of newly diagnosed HIV infections in
      conjunction with other data sources. Based on these surveillance data HIV
      incidence in Germany can be estimated to have been stable with 2000 to 2500 new
      infections per year since the early nineties, after having peaked in the early
      eighties. The most affected group are men who have sex with men followed by
      persons infected by heterosexual contact and migrants from high prevalence
      countries. The number of intravenous drug users has declined over the years and
      is now in fourth place. There are indications that increased risk behaviour and
      rising numbers of other sexually transmitted infections together with a change
      towards later initiation of antiretroviral therapy has led to an increase in new
      HIV infections in Germany in recent years. An improvement of the epidemiological
      surveillance for "indicator" STIs in combination with the assessment of risk
      behaviours in high risk groups would be desirable steps towards a second
      generation surveillance in Germany.

PMID- 17443298
TI  - [The role of endothelial progenitor cells in sepsis].
AB  - In sepsis and septic shock a series of immunological events are initiated that
      alter endothelial function in the macrocirculation and microcirculation.
      Endothelial swelling, deformation and apoptosis with detachment from the
      vasculature occur and endothelial cells (EC) appear in the circulation.
      Simultaneous to these pathological processes, reconstitution of the endothelial
      layer is initiated which can occur via migration and proliferation of surrounding
      mature ECs. However, terminally differentiated ECs have a low proliferative
      potential, hence their capacity to substitute damaged endothelium is limited.
      Therefore, adequate vascular repair requires additional support. Many studies
      have now convincingly demonstrated that vascular maintenance, repair,
      angiogenesis and neovascularization are partly mediated by recruitment of
      endothelial progenitor cells (EPCs) from the basal membrane. However, it seems
      that EPCs play a pivotal role not only in re-endothelialization after vascular
      damage, but also after severe inflammation. Recently, evidence was found that
      EPCs are increasingly mobilized during sepsis and that this mobilization is
      associated with clinical outcome. In septic patients the number of EPCs was
      significantly higher than in controls and was correlated with survival and the
      concentration of cytokines. In summary EPCs may exert an important function as an
      endogenous repair mechanism to maintain the integrity of the endothelial layer by
      replacing denuded parts of the microcirculation or by stimulation of EC
      proliferation. Therefore, EPC enumeration seems to be a valuable prognostic and
      diagnostic marker for the outcome in these patients and the induction of enhanced
      EPC mobilization a therapeutic option.

PMID- 17443299
TI  - [The value of postoperative ultrasonography].
AB  - In the early period following surgery, it is very important to reveal any
      complications. In this article the role of ultrasound in recognizing
      postoperative complications is demonstrated. Ultrasound findings in typical
      complications of abdominal surgery such as bleeding, abscess formation, acute
      cholecystitis, pancreatitis, and postoperative ileus are described. The diagnosis
      of postoperative bleeding, acute cholecystitis, and ileus is very reliable by
      ultrasound (sensitivity and specificity >95%). Ultrasonography is inferior to
      computed tomography in detecting pancreatitis and abscess formation. The guiding
      of interventions by ultrasound offers additional therapeutic options.

PMID- 17443300
TI  - [Endosonography of the gastrointestinal tract].
AB  - The clinical value of endosonography (EUS) in the gastrointestinal (GI) tract is
      currently increasing and supported by new imaging techniques. Conventional EUS
      combined with contrast application or elastography might further refine the
      diagnostic yield for GI cancers. The present review discusses current standards
      of EUS and endosonographically guided therapy and discusses newly available
      imaging modalities.

PMID- 17443301
TI  - [Free scapular or parascapular flaps for soft tissue damage accompanying talus or
      calcaneus fractures].
AB  - BASIS: Fractures of the talus or calcaneus with accompanying soft tissue damage
      require precisely planned treatment to prevent infection of the wound over time,
      especially in severely injured patients. MATERIAL AND METHODS: Seven patients
      with fractures of the talus or calcaneus and accompanying 2nd and 3rd degree open
      or 3rd degree closed soft tissue injuries were followed up retrospectively. These
      patients were operated on between January 1999 and January 2006 with free
      fasciocutaneous scapular or parascapular flaps. The average age was 34 (range 16
      54). Follow-up was at 6-36 months. RESULTS: Osteosynthesis was primarily in six
      cases, post-primarily in one, and in four cases exterior fixation was used
      additively. Temporary vacuum therapy was performed for a mean of 28 days (6-42).
      Parascapular, scapular, and Latissimus dorsi flap coverage was performed six,
      one, and one times, respectively. Six flaps healed without complication. One
      necrosis of a parascapular flap occurred and made a Latissimus dorsi flap
      necessary. In one case of donor-site wound dehiscense, a local rotation flap
      became necessary. There was no joint infection or osteomyelitis. Bony
      consolidation was achieved within all fractures. CONCLUSION: Traumatic soft
      tissue damage must be taken into account when primary or secondary internal
      fixation is performed and should influence the choice of implant. Free
      fasciocutaneous parascapular or scapular flaps are a powerful tool for preventing
      infection if local flaps are not sufficient to achieve stable soft tissue
      coverage.

PMID- 17443302
TI  - [Dysphagia and dyspnea after laparoscopic fundoplication].
AB  - Intrathoracic gastric herniation after laparoscopic antireflux surgery is a rare
      but well known phenomenon. It may occur during the early and late postoperative
      period. We report on a patient with early onset of dysphagia after surgery due to
      a tight wrap. Subsequent vomiting and dysphagia increased due to a gastric
      herniation. After gastroscopy and bougienage, tension pneumothorax developed. The
      context and relationships are illustrated and discussed referring to the current
      literature.

PMID- 17443303
TI  - [Twiddler's syndrome in a left pectoral implanted defibrillator].
AB  - Twiddler's syndrome describes a rare complication following implantation of a
      pacemaker/defibrillator and is characterized by spontaneous, repeated rotation of
      the generator in the subpectoral pocket. We describe the case of a 78-year-old
      man who presented with an exit block 7 months after defibrillator implantation.
      As cause, a 15-fold rotation of the defibrillator's generator around its own axis
      could be verified, which entailed dislocation of the defibrillator's electrode.
      Safe fixation of the electrode and generator in the subpectoral pocket is of
      paramount importance, particularly in patients with loose subcutaneous fatty
      tissue, to prevent this rare complication.

PMID- 17443304
TI  - [Painful soft-tissue swelling of the upper arm].
AB  - Cat-scratch disease is an infection by Bartonella henselea and resolves
      spontaneously. We present a case of untypical Bartonella infection which was
      misinterpreted by MRI as a soft-tissue sarcoma of the upper arm. The histological
      findings of an incision biopsy were unspecific, without signs of malignancy. The
      tumor was excised completely and the final histology, however, showed no evidence
      of malignant changes. The Bartonella henselae infection could be confirmed by
      polymerase chain reaction. The untypical presentation of cat-scratch disease
      should be considered in the differential diagnosis of clinically suspected soft
      tissue sarcoma.

PMID- 17443305
TI  - [Current recommendations in the treatment of basal cell carcinoma and squamous
      cell carcinoma of the skin].
AB  - The incidence of the most common tumors of the skin, basal cell carcinoma and
      squamous cell carcinoma, has risen rapidly in recent years. Dermatologists see in
      their daily practice many different clinical and histological variants of these
      tumors. They must be able to develop therapeutic strategies adapted to the tumor
      and the patient. Surgical excision remains the standard treatment. Micrographic
      histological evaluation should be employed in difficult locations, for large
      tumors and when there is increased risk of recurrence or metastasis. For initial
      or superficial lesions, other approaches such as radiation therapy, as well as
      curettage, cryosurgery, laser therapy and photodynamic therapy can be employed.
      An additional option is topical treatment with imiquimod or 5-flourouracil.

PMID- 17443307
TI  - Caps and gaps: a computer model for studies on brood incubation strategies in
      honeybees (Apis mellifera carnica).
AB  - In addition to heat production on the comb surface, honeybee workers frequently
      visit open cells ("gaps") that are scattered throughout the sealed brood area,
      and enter them to incubate adjacent brood cells. We examined the efficiency of
      this heating strategy under different environmental conditions and for gap
      proportions from 0 to 50%. For gap proportions from 4 to 10%, which are common to
      healthy colonies, we find a significant reduction in the incubation time per
      brood cell to maintain the correct temperature. The savings make up 18 to 37% of
      the time, which would be required for this task in completely sealed brood areas
      without any gaps. For unnatural high proportions of gaps (>20%), which may be the
      result of inbreeding or indicate a poor condition of the colony, brood nest
      thermoregulation becomes less efficient, and the incubation time per brood cell
      has to increase to maintain breeding temperature. Although the presence of gaps
      is not essential to maintain an optimal brood nest temperature, a small number of
      gaps make heating more economical by reducing the time and energy that must be
      spent on this vital task. As the benefit depends on the availability, spatial
      distribution and usage of gaps by the bees, further studies need to show the
      extent to which these results apply to real colonies.

PMID- 17443308
TI  - [Sellar tumors].
AB  - Because of the complex anatomy, examination of the sella turcica and hypophysis
      needs a dedicated MR sequence protocol. Not every sellar lesion is a pituitary
      adenoma. Thus, this review article summarizes the most frequently encountered
      intra-, supra-, and parasellar tumors and lesions. Differential diagnoses
      comprise besides adenoma among others craniopharyngioma, meningioma, glioma,
      germinoma, hamartoma, aneurysm, trigeminal schwannoma, pituitary carcinoma,
      chordoma, metastasis, infection, and empty sella. Characteristic imaging findings
      are presented and correlated to micro- and macro-pathology.

PMID- 17443309
TI  - Cytokine-induced osteoprotegerin expression protects pancreatic beta cells
      through p38 mitogen-activated protein kinase signalling against cell death.
AB  - AIMS/HYPOTHESIS: Pro-inflammatory cytokines play a crucial role in immune
      mediated beta cell destruction, an essential mechanism in the pathogenesis of
      type 1 diabetes mellitus. Microarray analysis recently identified osteoprotegerin
      (OPG; now known as tumour necrosis factor receptor superfamily, member 11b
      [TNFRSF11B]) as a cytokine-induced gene in beta cells. The aim of the present
      study was to characterise the functional role and signalling pathways of OPG that
      are involved in cytokine-induced beta cell death. MATERIALS AND METHODS: As
      cellular models, the rat beta cell line INS-1E and human primary pancreatic
      islets were employed. The effects of IL-1beta and TNF-alpha on OPG expression
      were characterised by northern blot and immunoassay. The effect of OPG on beta
      cell survival was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay. Signalling pathways were evaluated by western
      blot analysis using antibodies against p38 mitogen-activated protein kinases
      (MAPK), c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2.
      RESULTS: The INS-1E cell line and primary pancreatic islets expressed OPG mRNA
      and secreted OPG protein, both of which were enhanced by IL-1beta and TNF-alpha.
      Exposure to IL-1beta resulted in sustained phosphorylation of p38 MAPK in INS-1E
      cells and subsequent cell death. Administration of exogenous OPG prevented both
      IL-1beta-induced beta cell death and sustained p38 MAPK phosphorylation.
      CONCLUSIONS/INTERPRETATION: Our data indicate that cytokine-induced production of
      OPG may protect beta cells from further damage. This protective effect is, at
      least in part, mediated through inhibition of p38 MAPK phosphorylation. Thus OPG
      is an autocrine or paracrine survival factor for beta cells.

PMID- 17443310
TI  - Systemic and renal growth hormone-IGF1 axis involvement in a mouse model of type
      2 diabetes.
AB  - AIMS/HYPOTHESIS: In previous studies we have shown a significant involvement of
      the growth hormone (GH)-IGF axis in animal models of type 1 diabetes mellitus,
      but the role of this endocrine system in type 2 diabetes mellitus is less well
      characterised. We therefore examined the endocrine and renal GH-IGF axis changes
      in db/db mice, a model of type 2 diabetes mellitus and nephropathy. MATERIALS AND
      METHODS: Obese and lean animals were followed, beginning at hyperglycaemia onset,
      for 4 weeks. Albuminuria and creatinine clearance, as well as kidney and
      glomerular morphology were assessed. Tissue protein levels were determined by
      western blotting and mRNA levels by RT-PCR. RESULTS: Serum GH and IGF1 levels
      immediately prior to killing were decreased and liver mRNA levels of insulin-like
      growth factor binding protein 1 (Igfbp1) were increased in obese animals. Kidney
      weight was increased in obese animals, associated with hyperfiltration,
      albuminuria and glomerular hypertrophy. Administration of a somatostatin analogue
      (PTR-313) did not improve any of these parameters of diabetic renal involvement.
      Renal Igf1 mRNA was decreased and renal Igfbp1 mRNA and protein were
      significantly increased in obese animals. Renal insulin-driven levels of
      phosphorylated forkhead box O1 (FOXO1) were decreased in obese animals.
      CONCLUSIONS/INTERPRETATION: Diabetic db/db mice show significant renal changes
      (and IGFBP1 renal accumulation), similar to the findings in models of type 1
      diabetes mellitus. A decreased signalling through the insulin receptor and
      decreased FOXO1 phosphorylation may allow Igfbp1 gene transcription. These renal
      changes are associated with low circulating IGF1 and GH levels and unchanged
      hepatic growth hormone receptor expression, unlike the condition in type 1
      diabetes mellitus. This suggests that further GH inhibition to modulate renal
      complications in type 2 diabetes mellitus is not indicated.

PMID- 17443312
TI  - [Lengthening of proximal femoral focal deficiency using a hybrid fixation with
      inclusion of the knee joint].
AB  - BACKGROUND: A major problem in lengthening a short femur in proximal focal
      deficiency of the femur (PFFD) is the development of contractures and dislocation
      of the hip and knee joint. The knee joint is particularly prone to dislocation
      because of the cruciate ligament insufficiency associated with PFFD. Axis
      deviations also need specific attention. PATIENTS AND METHODS: In four patients
      (age 2.5-11 years) with PFFD (PAPPAS class III in one patient and VII in three
      patients), five femoral lengthenings with mechanical axis corrections were
      performed by the callotasis technique using a hybrid fixation system
      (Monotube/Triax) connecting the femur and the tibia with a fixed hinged knee
      joint to protect the knee against contracture and dislocation. RESULTS: All
      patients retained their hip and knee function. Hip flexion contracture during
      lengthening may make inclusion of the hip joint into the fixation system
      necessary, but was not carried out in the four patients presented. CONCLUSION:
      Four consecutive lengthenings of the femur with focal deficiency were carried out
      under protection by a hinged knee bridging external fixator. A dislocation could
      be prevented in all patients. We consider that such a system could be used during
      these lengthening procedures.

PMID- 17443313
TI  - Automated single-nucleotide polymorphism analysis using fluorescence excitation
      emission spectroscopy and one-class classifiers.
AB  - We have developed a new method of highly automated SNP (single nucleotide
      polymorphism) analysis for identification of genotypes. The data were generated
      by the Taqman reaction. A total of 18 half-plates were analysed for different
      genes, each consisting of 48 wells, including six synthetic DNA samples, three
      background samples, and 39 human DNA samples. Fluorescence spectra were obtained
      from each well. The characteristics of the spectra depended on whether the
      genotype originated from one of three classes-homozygotic wild-type, mutant, or
      heterozygote. The main problems are: (1) spectral variation from one half-plate
      to another is sometimes very substantial; (2) the spectra of heterozygotic
      samples vary substantially; (3) outliers are common; and (4) not all possible
      alleles are represented on each half-plate so the number of types of spectra can
      vary, depending on the gene being analysed. We solved these problems by using a
      signal-standardisation technique (piecewise direct standardisation, PDS) and then
      built two one-class classifiers based on PCA models (PCA data description) to
      identify the two types of homozygote. The remaining samples were tested to see
      whether they could be approximated well by a linear combination of the spectra of
      two types of homozygote. If they could, they were identified as heterozygotic; if
      not, they were identified as outliers. The results are characterised by very low
      false-positive errors and 2 to 6% overall false-negative errors.

PMID- 17443311
TI  - Association testing of common variants in the insulin receptor substrate-1 gene
      (IRS1) with type 2 diabetes.
AB  - AIMS/HYPOTHESIS: Activation of the insulin receptor substrate-1 (IRS1) is a key
      initial step in the insulin signalling pathway. Despite several reports of
      association of the G972R polymorphism in its gene IRS1 with type 2 diabetes, we
      and others have not observed this association in well-powered samples. However,
      other nearby variants might account for the putative association signal. SUBJECTS
      AND METHODS: We characterised the haplotype map of IRS1 and selected 20 markers
      designed to capture common variations in the region. We genotyped this
      comprehensive set of markers in several family-based and case-control samples of
      European descent totalling 12,129 subjects. RESULTS: In an initial sample of
      2,235 North American and Polish case-control pairs, the minor allele of the
      rs934167 polymorphism showed nominal evidence of association with type 2 diabetes
      (odds ratio [OR] 1.25, 95% CI 1.03-1.51, p = 0.03). This association showed a
      trend in the same direction in 7,659 Scandinavian samples (OR 1.16, 95% CI 0.96
      1.39, p = 0.059). The combined OR was 1.20 (p = 0.008), but statistical
      correction for the number of variants examined yielded a p value of 0.086. We
      detected no differences across rs934167 genotypes in insulin-related quantitative
      traits. CONCLUSIONS/INTERPRETATION: Our data do not support an association of
      common variants in IRS1 with type 2 diabetes in populations of European descent.

PMID- 17443314
TI  - Analytical development for analysis of pharmaceuticals in water samples by SPE
      and GC-MS.
AB  - An analytical procedure involving solid-phase extraction (SPE) and gas
      chromatography-mass spectrometry (GC-MS) has been developed for determination of
      pharmaceutical compounds (aspirin, caffeine, carbamazepine, diclofenac,
      ketoprofen, naproxen, ibuprofen, clofibrate, clofibric acid, and gemfibrozil) in
      a variety of aqueous samples (wastewater and surface water). After filtration,
      samples were extracted and concentrated using C(18) or HLB cartridges, depending
      on the type of compound. Sample storage conditions were checked and optimized to
      ensure preservation of the pharmaceutical substance, taking into consideration
      environmental sampling conditions. For most of the pharmaceuticals monitored,
      recovery was in the range 53 to 99% and the variability was below 15% for the
      complete procedure, with limits of detection ranging from 0.4 to 2.5 ng L(-1),
      depending on the compound. The methods were successfully applied to monitoring of
      pharmaceutical contamination of the Seine estuary. Concentrations varied from
      several dozens of nanograms per liter for surface waters to several hundreds of
      nanograms per liter for wastewaters.

PMID- 17443315
TI  - Unilateral reaction time task is delayed during contralateral movements.
AB  - Performing unlearned unimanual tasks when simultaneously carrying out another
      task with the contralateral hand is known to be difficult. The dual task
      interference theory predicts that reaction time will be delayed if the
      investigated task is performed in the course of ongoing contralateral movements.
      Ballistic movements can be performed at maximal speed in simple reaction time
      (SRT) experiments when subjects have adequately prepared the motor system needed
      for movement execution. When fully prepared, activation of subcortical motor
      pathways by a startling auditory stimulus (SAS) triggers the whole reaction. In
      this study, we have examined dual task interference with reaction time in eight
      healthy volunteers. They were presented with a visual imperative signal to
      perform unilateral SRT either in a baseline condition (control trials) or while
      carrying out contralateral rhythmic oscillatory movements (test trials). A SAS
      was introduced in 25% of the trials in both conditions. SRT was significantly
      delayed in the interference test trial when compared to control trials either
      with or without SAS (P<0.001). Control and test trials with SAS were
      significantly faster than those without SAS in both conditions (P<0.001).
      However, there were no significant differences in the percentage SRT shortening
      induced by SAS or in the percentage SRT delay observed in the test trials. Our
      results suggest that performing rhythmic oscillatory movements with one limb
      slows SRT in the contralateral limb and that this effect is likely related to
      motor preparation changes. The effect described here can be of interest for
      physiological studies of interlimb coordination and the mechanisms underlying the
      dual task interference phenomenon.

PMID- 17443316
TI  - Error compensation during finger force production after one- and four-finger
      voluntarily fatiguing exercise.
AB  - The effect of muscle fatigue on error compensation strategies during multi-finger
      ramp force production tasks was investigated. Thirteen young, healthy subjects
      were instructed to produce a total force with four fingers of the right hand to
      accurately match a visually displayed template. The template consisted of a 3-s
      waiting period, a 3-s ramp force production [from 0 to 30% maximal voluntary
      contraction (MVC)], and a 3-s constant force production. A series of 12 ramp
      trials was performed before and after fatigue. Fatigue was induced by a 60-s
      maximal isometric force production with either the index-finger only or with all
      four fingers during two separate testing sessions. The average percent of drop
      was 38.2% in the MVC of the index finger after index-finger fatiguing exercise
      and 38.3% in the MVC of all fingers after four-finger fatiguing exercise. The
      ability of individual fingers to compensate for each other's errors in order for
      the total force to match the preset template was quantified as the error
      compensation index (ECI), i.e., the ratio of the sum of variances of individual
      finger forces and the variance of the total force. By comparing pre- and post
      fatigue performance during four-finger ramp force production, we observed that
      the variance of the total force was not significantly changed after one- or four
      finger fatiguing exercise. The ECI significantly decreased after four-finger
      fatiguing exercise, especially during the last second of the ramp; while the ECI
      remained unchanged after index finger single-finger fatiguing exercise. These
      results suggest that the central nervous system is able to utilize the abundant
      degrees of freedom to compensate for partial impairment of the motor apparatus
      induced by muscle fatigue to maintain the desired performance. However, this
      ability is significantly decreased when all elements of the motor apparatus are
      impaired.

PMID- 17443318
TI  - A 6F guide sheath for endovascular treatment of intracranial aneurysms.
AB  - INTRODUCTION: Stable insertion of guide catheters via the femoral route can prove
      difficult because of tortuous vasculature leading to failure of endovascular
      treatment of intracranial aneurysms. METHODS AND RESULTS: We report our
      experience using a long braided introducer sheath (6F Terumo Destination) with an
      inner diameter of 0.087 inches. It allowed the simultaneous use of multiple
      catheters or adjunctive techniques (balloon-assisted or stent-assisted coiling)
      while providing excellent support in 60 procedures involving coiling of anterior
      circulation aneurysms. CONCLUSION: The use of a long introducer sheath, by
      enhancing stability in the aortic arch and supraaortic vessels, provides another
      solution to the problem of vascular tortuosity that hinders endovascular
      treatment of intracranial lesions.

PMID- 17443317
TI  - Activity of primate orbitofrontal and dorsolateral prefrontal neurons: task
      related activity during an oculomotor delayed-response task.
AB  - The orbitofrontal cortex (OFC) has strong reciprocal connections to the
      dorsolateral prefrontal cortex (DLPFC), which is known to participate in spatial
      working memory processes. However, it is not known whether or not the OFC also
      participates in spatial working memory and whether the OFC and DLPFC contribute
      equally to this process. To address these issues, we collected single-neuron
      activity from both areas while a monkey performed an oculomotor delayed-response
      task, and compared the characteristics of task-related activities between the OFC
      and DLPFC. All of the task-related activities observed in the DLPFC were also
      observed in the OFC. However, the proportion and response characteristics of task
      related activities were different between the two areas. While most delay-period
      activity observed in the DLPFC was directionally selective and showed tonic
      sustained activation, most delay-period activity observed in the OFC was omni
      directional and showed gradually increasing activity. Reward-period activity was
      predominant among task-related activities in the OFC. The proportion of neurons
      showing reward-period activity was significantly higher in the OFC than in the
      DLPFC. These results suggest that, although both the OFC and DLPFC participate in
      spatial working memory processes, the OFC is related more to the expectation and
      the detection of reward delivery, while the DLPFC is related more to the
      temporary maintenance of spatial information and its processing.

PMID- 17443319
TI  - NTP-binding properties of the blue-light receptor YtvA and effects of the E105L
      mutation.
AB  - YtvA is a blue-light-sensing protein from Bacillus subtilis related to plant
      phototropins. It carries a LOV (light, oxygen and voltage) domain, binding FMN
      (flavin mononucleotide) as chromophore, and a STAS (sulphate transporters and
      antisigma-factor antagonists) domain with poorly characterized function. We have
      recently shown that YtvA binds triphosphate nucleotides (NTP) and highlighted a
      structural similarity between the STAS domain and small GTP-binding proteins. In
      this work we further investigated the NTP-binding properties of YtvA, employing a
      fluorescent derivative of GTP (GTP(TR)) and mutagenesis experiments. The main
      results are as follows: (a) competition experiments indicate that the affinity of
      YtvA for GTP is much higher than that for GDP and GMP. (b) Blue-light-induced
      structural changes are transmitted from the LOV core to the NTP-binding cavity,
      establishing a possible intraprotein signal-transduction pathway. (c) A mutation
      in the central beta-scaffold of the LOV core, E105L, impairs the light-driven
      spectroscopic changes of bound GTP(TR). This result is supported by circular
      dichroism data, in that YtvA-E105L does not show the light-induced conformational
      change in the turn fraction that characterizes YtvA, implying that E105 is
      functionally important. (d) In the structural model of the LOV-STAS complex,
      based on docking algorithms, the interface includes the Ibeta-Hbeta loop on the
      LOV core, as well as parts of the central beta-scaffold. E105 is predicted to
      interact with the LOV-STAS linker region, suggested to play a role in phototropin
      signaling.

PMID- 17443320
TI  - Protonation linked equilibria and apparent affinity constants: the thermodynamic
      profile of the alpha-chymotrypsin-proflavin interaction.
AB  - Protonation/deprotonation equilibria are frequently linked to binding processes
      involving proteins. The presence of these thermodynamically linked equilibria
      affects the observable thermodynamic parameters of the interaction (K(obs),
      DeltaH(obs)(0) ). In order to try and elucidate the energetic factors that govern
      these binding processes, a complete thermodynamic characterisation of each
      intrinsic equilibrium linked to the complexation event is needed and should
      furthermore be correlated to structural information. We present here a detailed
      study, using NMR and ITC, of the interaction between alpha-chymotrypsin and one
      of its competitive inhibitors, proflavin. By performing proflavin titrations of
      the enzyme, at different pH values, we were able to highlight by NMR the effect
      of the complexation of the inhibitor on the ionisable residues of the catalytic
      triad of the enzyme. Using ITC we determined the intrinsic thermodynamic
      parameters of the different equilibria linked to the binding process. The
      possible driving forces of the interaction between alpha-chymotrypsin and
      proflavin are discussed in the light of the experimental data and on the basis of
      a model of the complex. This study emphasises the complementarities between ITC
      and NMR for the study of binding processes involving protonation/deprotonation
      equilibria.

PMID- 17443321
TI  - Continuous production of chiral 1,3-butanediol using immobilized biocatalysts in
      a packed bed reactor: promising biocatalysis method with an asymmetric hydrogen
      transfer bioreduction.
AB  - An asymmetric hydrogen-transfer biocatalyst consisting of mutated Rhodococcus
      phenylacetaldehyde reductase (PAR) or Leifsonia alcohol dehydrogenase (LSADH) was
      applied for some water-soluble ketone substrates. Among them, 4-hydroxy-2
      butanone was reduced to (S)/(R)-1,3-butanediol, a useful intermediate for
      pharmaceuticals, with a high yield and stereoselectivity. Intact Escherichia coli
      cells overexpressing mutated PAR (Sar268) or LSADH were directly immobilized with
      polyethyleneimine or 1,6-diaminehexane and glutaraldehyde and evaluated in a
      batch reaction. This system produced (S)-1,3-butanediol [87% enantiomeric excess
      (e.e.)] with a space time yield (STY) of 12.5 mg h(-1) ml(-1) catalyst or (R)-1,3
      butanediol (99% e.e.) with an STY of 60.3 mg h(-1) ml(-1) catalyst, respectively.
      The immobilized cells in a packed bed reactor continuously produced (R)-1,3
      butanediol with a yield of 99% (about 49.5 g/l) from 5% (w/v) 4-hydroxy-2
      butanoate over 500 h.

PMID- 17443322
TI  - Clinical quality management in telenuclear medicine.

PMID- 17443323
TI  - DC immunotherapy is highly effective for the inhibition of tumor metastasis or
      recurrence, although it is not efficient for the eradication of established solid
      tumors.
AB  - Dendritic cell (DC)-based immunotherapy has not been as effective as expected in
      most solid tumors even in the murine model, particularly in renal cell carcinoma
      (RCC). Our investigation was initiated to identify what causes the limitations of
      DC-based immunotherapy in solid RCC. We have investigated immunosuppressive
      factors from tumors and their effects on DC migration, as well as cytotoxic T
      lymphocyte (CTL) response and lymphocyte infiltration into the tumor mass upon
      vaccination with mouse renal adenocarcinoma (Renca) cell lysate-pulsed bone
      marrow (Bm)-derived DC in tumor-bearing mice. We also investigated pulmonary
      metastasis- and tumor recurrence-inhibitory effects of DC-vaccination in the
      solid tumor-bearing mice. In these experiments, we found that the limitations of
      DC-based immunotherapy to solid RCC likely result from tumor-mediated TGF-beta
      hindrance of immune attack rather than insufficient immune induction by DC
      therapy. In fact, the CTL response induced by DC therapy was quite sufficient and
      functional for the inhibition of tumor recurrence after surgery or of tumor
      metastasis induced by additional tumor-challenge to the tumor-bearing mice. Taken
      together, our present results obtained in mouse model suggest the potential of DC
      immunotherapy in tumor patients for hindering or blocking disease progression by
      inhibition of tumor metastasis and/or tumor recurrence after surgery.

PMID- 17443324
TI  - Total hip arthroplasties: what are the reasons for revision?
AB  - Primary total hip arthroplasties have reported success rates of greater than 95%
      in many series with a longer than 10-year follow-up. Revision total hip
      arthroplasty due to such factors as increased high-activity levels, younger
      patients undergoing the procedure and increasing life expectancy has become more
      prevalent. An understanding of the mechanisms and timing of total hip
      arthroplasty failure can direct efforts aimed at reducing revision rates. This
      study was conducted to evaluate the indications for revision hip arthroplasty and
      relate these to the time after the index primary hip arthroplasty. A review of
      all revision hip arthroplasties at two centres over a 6-year time period
      identified 225 patients who underwent 237 revisions. The overall mean time to
      revision was 83 months (range: 0-360 months). The cause of failure was aseptic
      loosening in 123 hips (51.9%), instability in 40 hips (16.9%) and infection in 37
      hips (5.5%). When stratified into two groups (less than 5 years, more than 5
      years after the index primary hip arthroplasty), 118 of 237 (50%) revisions
      occurred in less than 5 years, with 33% due to instability and 24% resulting from
      infection. The majority of the causes of failure within 5 years in these early
      revisions were instability and deep infection. The success of hip arthroplasty is
      likely to be compromized if technical aspects of the surgery for appropriate
      component positioning and critical protocols to minimise complications such as
      infection are not given the proper attention.

PMID- 17443325
TI  - Pharmacokinetics of gemcitabine in tumor and non-tumor extracellular fluid of
      brain: an in vivo assessment in rats employing intracerebral microdialysis.
AB  - PURPOSE: Gemcitabine is a pyrimidine nucleoside analogue anticancer agent that
      has shown promising anti-tumor activity in several experimental models of brain
      tumor. However, the pharmacokinetic behavior of gemcitabine in the central
      nervous system, especially in brain tumors is currently not well understood. In
      this study we evaluated the gemcitabine brain extracellular fluid (ECF) in normal
      rats and in ECF obtained from tumor- and tumor-free regions of glioma-bearing
      rats, to better understand the availability of the drug to brain and brain
      tumors. METHODS: The brain ECF pharmacokinetics of gemcitabine were investigated
      employing intracerebral microdialysis following intravenous administration of 10,
      25 and 100 mg/kg doses in male Sprague-Dawley rats. In the second phase of the
      study, gemcitabine (25 mg/kg) was intravenously administered in rats implanted
      with C6 gliomas and ECF samples were simultaneously obtained from the tumor and
      tumor-free regions of the brain. Serial blood samples were obtained for
      evaluating the plasma pharmacokinetics of gemcitabine. Non-compartmental approach
      was employed for the analyses of the brain ECF and plasma pharmacokinetics of
      gemcitabine. RESULTS: Following intravenous administration, gemcitabine rapidly
      distributed into rat brain. At doses equivalent to 10, 25 and 100 mg/kg, the
      brain ECF gemcitabine AUC (area under the plasma concentration--time curve
      measured over the last sampling time point) values were 2.46 +/- 0.7, 3.20 +/-
      1.1, and 9.06 +/- 3.0 microg h/ml, respectively. The brain ECF concentrations of
      gemcitabine declined in parallel with plasma concentrations. At the three doses
      evaluated, the relative brain distribution coefficient (AUC brainECF/AUC plasma)
      of gemcitabine ranged from 0.07 to 0.09 suggesting limited gemcitabine
      availability to brain tissues. Studies on C6 glioma-bearing rats revealed that
      following an intravenous dose of 25 mg/kg, the AUC values in the tumor-free and
      tumor-brain regions were 4.52 +/- 2.4, and 9.82 +/- 3.3 microg h/ml,
      respectively. Thus, the AUC of gemcitabine in the tumor ECF was on average 2.2
      fold greater than the corresponding value in the tumor-free ECF of the brain.
      Plasma pharmacokinetics of gemcitabine remained unaltered in tumor-bearing
      animals, when compared to plasma pharmacokinetics in healthy animals.
      CONCLUSIONS: Our findings suggest that the overall brain exposure to gemcitabine
      is likely to be low as evident from the relative brain distribution coefficient
      of <0.1. However, the exposure is likely to be considerably higher in the brain
      tumor relative to tumor-free regions of the brain. The higher drug levels in
      brain tumor compared to the non-tumor region may facilitate selectively higher
      cytotoxicity against brain tumor cells.

PMID- 17443326
TI  - Ankylosing spondylitis in a patient with Turner syndrome: a case report.
AB  - Turner's syndrome (TS) is a chromosomal disorder where phenotypic females have
      either a missing chromosome (45 X0) or a structural aberration of one of the
      chromosomes. It is possible for TS to accompany such autoimmune diseases as
      thyroid diseases, inflammatory intestinal diseases, diabetes mellitus, psoriatic
      arthritis and juvenile rheumatoid arthritis. Herein, we present an unusual case
      with Ankylosing spondylitis (AS) and autoimmune thyroiditis associated with TS.
      We suggest that the possibility that TS patients may also develop such other
      diseases as AS apart from the already known accompanying autoimmune diseases
      should not be ruled out when monitoring TS patients.

PMID- 17443327
TI  - Severe, refractory, non-malignant type I cryoglobulinemia treated with
      alemtuzumab.
AB  - A 41 year old female with type I cryoglobulinemia, refractory to
      methylprednisolone, rituximab, and cyclophosphamide complicated by a rising serum
      viscosity was treated with alemtuzumab. After a cumulative dose of 1,085 mg of
      alemtuzumab, her serum viscosity decreased to normal. Treatment toxicity was
      limited to fungal esophagitis responsive to topical therapy. This case
      demonstrates the potential use of alemtuzumab in the treatment of refractory
      cryoglobulinemia.

PMID- 17443328
TI  - Serum oxidative-antioxidative status in patients with ankylosing spondilitis.
AB  - Ankylosing spondylitis (AS) is an inflammatory disorder with unknown etiology
      that mainly affects the axial skeleton as well as the peripheral joints and extra
      articular structures. The aim of this study was to evaluate the total antioxidant
      status (TAS), total oxidative status (TOS) and oxidative stress index (OSI) in
      patients with ankylosing spondylitis (AS). Fifty AS patients with a mean Bath AS
      Activity Index (BASDAI) 4.6 (range 4-9.3) and 26 healthy controls were included
      in the study. Plasma TAS, TOS levels were determined by using novel automated
      methods. The OSI was calculated. Plasma TOS level and OSI values were
      significantly higher, and plasma TAS level was lower in patients than in healthy
      controls (15.8 +/- 4. 9 vs. 4.3 +/- 2.8, 12.8 +/- 3. 9 vs. 9.6 +/- 5.5, 1.2 +/-
      0.03 vs. 1.8 +/- 0.2, respectively, P < 0.001 for all). There was no significant
      correlation between oxidant/antioxidant parameters and disease activity. The
      results of this study indicated that increased oxidant and decreased antioxidant
      capacity may be associated with the pathogenesis of AS.

PMID- 17443329
TI  - Serum leptin in rheumatoid arthritis.
AB  - Leptin is a peptide hormone that has an essential role in the regulation of body
      weight by inhibiting food intake and stimulating energy expenditure. The role of
      leptin in the modulation of the immune response and inflammation has been
      regarded as important. In rheumatoid arthritis (RA) patients it was reported that
      fasting leads to an improvement of clinical and biological measures of disease
      activity, which was associated with a marked decrease in serum leptin. These
      features suggest that leptin may also influence the inflammatory mechanisms of
      arthritis in humans. In this study we assessed serum leptin levels in RA and
      osteoarthritis (OA) patients and found a correlation between serum leptin level
      and other markers as well as bone mass density changes, activity of disease,
      disease duration and the age of the patients. The blood was collected from 30 RA
      and 30 OA patients who constituted the control group. Serum leptin level was
      determined using the DRG Leptin ELISA Kit-a solid phase enzyme-linked
      immunosorbent assay based on the sandwich principle. The serum level of leptin in
      RA patients ranged from 1.8 to 81.1 ng/ml and median value was 11.2. There was a
      positive correlation between body mass index (BMI) of RA patients and serum level
      of leptin (correlation coefficients Spearman's r = 0.81). According to
      correlation coefficients, serum leptin level is independent of age of RA
      patients, stage of disease, number of painful and swollen joints, duration of
      morning stiffness, disease duration as well as value of titre of the Waaler-Rose,
      disease activity score (DAS 28) value and presence of rheumatoid nodules. There
      was a negative correlation between serum leptin level and glomerular filtration
      rate (GFR). No correlation between the serum leptin level and T-score was found.
      An influence of steroid treatment on the serum leptin level was not shown. The
      median serum leptin level in OA patients was 9.2 ng/ml. There was a positive
      correlation between body mass index of OA patients and serum level of leptin
      (correlation coefficients Spearman's r = 0.57). No correlation was found between
      serum leptin level and patient's age, duration of disease and value of laboratory
      data. There were no correlations between serum leptin level and visual analogue
      pain scale (VAS) for the lower-limb afflicted patients as well as stage of
      disease according to Kellgren and Lawrence's score in OA patients. There was a
      negative correlation between serum leptin level and T-score value in OA patients
      (r = -0.58, P < 0.05). No statistically significant differences were found
      between serum leptin levels for RA and OA patients.

PMID- 17443330
TI  - Asymmetric somatic hybridization between UV-irradiated Citrus unshiu and C.
      sinensis: regeneration and characterization of hybrid shoots.
AB  - In the present paper, attempts were made to explore the possibility of employing
      ultraviolet (UV) irradiation in citrus asymmetric fusion for transfer of limited
      amount of favorable traits from a desirable cultivar to a target one. Exposure of
      Satsuma mandarin (Citrus unshiu Marc.) embryogenic protoplasts to UV at an
      intensity of 300 muW cm(-2) led to reduced viability, especially under long
      irradiation duration. The protoplasts could not grow during culture when they
      were irradiated for over 30 s. Terminal deoxynucleotidyl transferase biotin-dUTP
      nick end labeling (TUNEL) assay revealed extensive DNA fragmentation in the UV
      irradiated protoplasts compared with those without UV treatment. Electrofusion
      between UV-irradiated protoplasts of Satsuma mandarin (donor) with those of
      Jincheng (C. sinensis Osbeck, recipient), a local cultivar of superior quality,
      gave rise to regeneration of several lines of shoots, which failed to root
      despite enormous endeavors. Ploidy analysis via flow cytometry and chromosome
      counting showed that four selected shoots were either diploid, triploid or
      tetraploid. Random amplified polymorphism DNA (RAPD) and amplified fragment
      length polymorphism (AFLP) confirmed the shoots, irrespective of their ploidy
      level, as putative somatic hybrids. Cleaved amplified polymorphism sequences
      (CAPS) demonstrated that the shoots predominantly got their cytoplasmic
      components, in terms of chloroplast (cp) and mitochondrion DNA, from Jincheng,
      along with possible recombination of cpDNA in some shoot lines. The current data
      indicated that UV-based asymmetric fusion could also be employed in citrus
      somatic hybridization with the intention of creating novel germplasms, which may
      provide an alternative approach for cultivar improvement.

PMID- 17443331
TI  - Myocardial tagging with steady state free precession techniques and semi
      automatic postprocessing--impact on diagnostic value.
AB  - Our aim was to determine the diagnostic value of myocardial tagging sequences
      with regard to the evaluable share of the cardiac cycle. Thirty-three patients
      were examined at 1.5 T using tagging sequences with gradient-echo (GRE) readout,
      18 patients at 1.5 T with steady-state free precession (SSFP), and 11 patients at
      3 T using GRE. Two observers graded image quality and determined the share of the
      cardiac cycle for which postprocessing could be performed (1, optimal; 2, little
      interaction; 3, whole cycle assessable; 4, diastole non-assessable; 5, systole
      incomplete; 6, non-diagnostic). With GRE at 1.5 T, median image quality was 4.0
      (95% CI 4.0-5.0), while it was significantly better with 2.0 (2.0-3.0) using the
      SSFP technique and similar at 3 T with 2.9 (1.7-3.5). With GRE at 1.5 T, systole
      could be assessed in 69% of patients, and an evaluation of the whole cardiac
      cycle was not possible. With the SSFP sequence at 1.5 T and GRE at 3 T, an
      evaluation of the whole cardiac cycle was possible in 71% and 70% of the
      patients, respectively, and systole was assessable in all patients. Tagging
      sequences with SSFP readout at 1.5 T make a semi-automatic evaluation of the
      whole cardiac cycle feasible in a large share of patients.

PMID- 17443332
TI  - [Treatment of pseudophakic cystoid macular edema].
AB  - Pseudophakic cystoid macular edema (PCME) is the most common complication
      following cataract surgery. In 1-3% of cases it is associated with a decrease in
      visual acuity. However, PCME has a good prognosis, persisting in only 10% of the
      patients beyond 2 years. The prophylactic therapy of eyes without additional
      disease with non-steroidal antiphlogistic drugs or steroids does not influence
      the final visual acuity. Under certain circumstances, prophylaxis can be a
      reasonable option. Risk factors that promote the formation of PCME are discussed.
      The course of acute or chronic PCME can be influenced by drug treatment, but in
      general the level of evidence for the treatment of this widespread problem is
      low. We would therefore like to present the Freiburg treatment scheme for PCME
      for discussion.

PMID- 17443333
TI  - Inflammatory myofibroblastic tumor of the bladder in children: what can be
      expected?
AB  - Inflammatory myofibroblastic tumor of the bladder is an uncommon condition of
      unknown neoplastic potential. In adults the tumor is seen in association with
      instrumentation of the lower genitourinary tract, while in children it appears to
      run an idiopathic course. Its clinical and radiological presentation in children
      resembles sarcoma. The case of a 10-year-old girl with inflammatory
      myofibroblastic tumor is presented, outlining the histological and
      immunhistochemical features to allow differentiation between sarcomas, the most
      important differential diagnosis. An outcome meta-analysis of the literature
      identified 35 cases of inflammatory myofibroblastic tumor in the bladder of
      children. Conservative surgery is the strategy of choice. There is no evidence of
      recurrence or metastasis at a median follow up of 1.5 years.

PMID- 17443334
TI  - The dentate nucleus in Friedreich's ataxia: the role of iron-responsive proteins.
AB  - Frataxin deficiency in Friedreich's ataxia (FRDA) causes cardiac, endocrine, and
      nervous system manifestations. Frataxin is a mitochondrial protein, and adequate
      amounts are essential for cellular iron homeostasis. The main histological lesion
      in the brain of FRDA patients is neuronal atrophy and a peculiar proliferation of
      synaptic terminals in the dentate nucleus termed grumose degeneration. This
      cerebellar nucleus may be especially susceptible to FRDA because it contains
      abundant iron. We examined total iron and selected iron-responsive proteins in
      the dentate nucleus of nine patients with FRDA and nine normal controls by
      biochemical and microscopic techniques. Total iron (1.53 +/- 0.53 mumol/g wet
      weight) and ferritin (206.9 +/- 46.6 mug/g wet weight) in FRDA did not
      significantly differ from normal controls (iron: 1.78 +/- 0.88 mumol/g; ferritin:
      210.9 +/- 9.0 mug/g) but Western blots exhibited a shift to light ferritin
      subunits. Immunocytochemistry of the dentate nucleus revealed loss of
      juxtaneuronal ferritin-containing oligodendroglia and prominent ferritin
      immunoreactivity in microglia and astrocytes. Mitochondrial ferritin was not
      detectable by immunocytochemistry. Stains for the divalent metal transporter 1
      confirmed neuronal loss while endothelial cells reacting with antibodies to
      transferrin receptor 1 protein showed crowding of blood vessels due to collapse
      of the normal neuropil. Regions of grumose degeneration were strongly reactive
      for ferroportin. Purkinje cell bodies, their dendrites and axons, were also
      ferroportin-positive, and it is likely that grumose degeneration is the
      morphological manifestation of mitochondrial iron dysmetabolism in the terminals
      of corticonuclear fibers. Neuronal loss in the dentate nucleus is the likely
      result of trans-synaptic degeneration.

PMID- 17443335
TI  - Continuous spinal analgesia and anesthesia following accidental dural puncture in
      the parturient.

PMID- 17443336
TI  - Acceptance and long-term compliance of nCPAP in obstructive sleep apnea.
AB  - In a retrospective cohort study, we evaluated whether improvements in nasal
      continuous positive airway pressure (nCPAP) technology, particularly the
      introduction of automatic adjustment of the nCPAP pressure (auto-CPAP), have led
      to better acceptance and (long-term) compliance in patients with obstructive
      sleep apnea syndrome (OSAS) as compared to earlier reported data. Questionnaires
      were sent to 256 patients, who were referred to our clinic for an overnight
      polysomnography from January 1997 to July 2005 and received nCPAP therapy for
      OSAS. Of the 256 patients, 24 patients were unavailable for follow-up. Of the
      remaining 232 patients, 58 patients (25%) had discontinued therapy, while 174
      patients (75%) were still using nCPAP after 2 months to 8 years of follow-up. One
      Hundred and thirty eight (79%) of these 174 patients used nCPAP for at least 4
      h/night during >or= 5 nights/week, 82,1% of the conventional nCPAP (fixed
      pressure CPAP) group (n = 78) and 77,1% of the auto-CPAP group (n = 96).
      Therefore, including the 58 failures, only 59.5% of patients can be seen as
      compliant. There were no statistical differences between the fixed pressure CPAP
      and auto-CPAP users, and between the compliant and non-compliant users according
      to age, BMI, AHI and Epworth sleepiness scale (ESS). Auto-CPAP patients used
      significantly more cm H2O. The long-term compliance of nCPAP therapy has have
      increased only slightly since the introduction of the fixed pressure CPAP 25
      years ago, in spite of many efforts to improve it. It seems that a plateau has
      been reached and that it is unrealistic to aim at a substantially higher
      compliance rate.

PMID- 17443337
TI  - The clinical significance of atypia in thyroid fine-needle aspiration.
AB  - Fine-needle aspiration cytology (FNAC) of thyroid nodules has become the primary
      diagnostic tool in the evaluation of thyroid nodules. However, the diagnostic
      utility of thyroid cytology may be limited by the presence of atypical cytologic
      patterns. In patients with atypical cytology in FNAC, treatment concept is not
      established. The purpose of this study is to correlate subcategories of atypical
      cytology of thyroid gland with final histologic diagnoses, and to help develop a
      treatment plan for thyroid nodules. We retrospectively reviewed 133 specimens of
      patients with atypical cytology of thyroid nodule according to preoperative FNAC.
      The atypical cytologic patterns were classified and divided into three groups:
      follicular neoplasm with nuclear atypia (FNA), nodular hyperplasia with nuclear
      atypia (NHA), possible papillary carcinoma (PP). Then we investigated the
      malignancy rates of each group. Among the 133 specimens with atypical cytology,
      43 cases (32.3%) were proved to be malignant. Of the 97 cases in the FNA group,
      29.9% were malignant. In the NHA and PP groups, 23.1 and 47.8% were malignant,
      respectively. However, there was no statistical significance in the incidence of
      malignancy among the three groups. There was also no statistical difference among
      all groups, with regard to lymph node metastasis and recurrence. In conclusion,
      if aspirates manifest atypical cytologic pattern, surgery should be considered,
      especially if the results are categorized as PP. Intraoperative frozen section
      should be confirmed and the extent of resection should be determined by final
      pathology.

PMID- 17443338
TI  - Biodosimetry estimate for high-LET irradiation.
AB  - The purpose of this paper is to prepare for an easy and reliable biodosimeter
      protocol for radiation accidents involving high-linear energy transfer (LET)
      exposure. Human peripheral blood lymphocytes were irradiated using carbon ions
      (LET: 34.6 keV microm(-1)), and the chromosome aberrations induced were analyzed
      using both a conventional colcemid block method and a calyculin A induced
      premature chromosome condensation (PCC) method. At a lower dose range (0-4 Gy),
      the measured dicentric (dics) and centric ring chromosomes (cRings) provided
      reasonable dose information. At higher doses (8 Gy), however, the frequency of
      dics and cRings was not suitable for dose estimation. Instead, we found that the
      number of Giemsa-stained drug-induced G2 prematurely condensed chromosomes (G2
      PCC) can be used for dose estimation, since the total chromosome number
      (including fragments) was linearly correlated with radiation dose (r = 0.99). The
      ratio of the longest and the shortest chromosome length of the drug-induced G2
      PCCs increased with radiation dose in a linear-quadratic manner (r = 0.96), which
      indicates that this ratio can also be used to estimate radiation doses.
      Obviously, it is easier to establish the dose response curve using the PCC
      technique than using the conventional metaphase chromosome method. It is assumed
      that combining the ratio of the longest and the shortest chromosome length with
      analysis of the total chromosome number might be a valuable tool for rapid and
      precise dose estimation for victims of radiation accidents.

PMID- 17443340
TI  - Depth, contrast and view-based homing in outdoor scenes.
AB  - Panoramic image differences can be used for view-based homing under natural
      outdoor conditions, because they increase smoothly with distance from a reference
      location (Zeil et al., J Opt Soc Am A 20(3):450-469, 2003). The particular shape,
      slope and depth of such image difference functions (IDFs) recorded at any one
      place, however, depend on a number of factors that so far have only been
      qualitatively identified. Here we show how the shape of difference functions
      depends on the depth structure and the contrast of natural scenes, by quantifying
      the depth- distribution of different outdoor scenes and by comparing it to the
      difference functions calculated with differently processed panoramic images,
      which were recorded at the same locations. We find (1) that IDFs and catchment
      areas become systematically wider as the average distance of objects increases,
      (2) that simple image processing operations -- like subtracting the local mean,
      difference-of-Gaussian filtering and local contrast normalization -- make
      difference functions robust against changes in illumination and the spurious
      effects of shadows, and (3) by comparing depth-dependent translational and depth
      independent rotational difference functions, we show that IDFs of contrast
      normalized snapshots are predominantly determined by the depth-structure and
      possibly also by occluding contours in a scene. We propose a model for the shape
      of IDFs as a tool for quantitative comparisons between the shapes of these
      functions in different scenes.

PMID- 17443339
TI  - Polyamines in spermatocytes and residual bodies of rat testis.
AB  - Immunocytochemistry for polyamines in the rat testis revealed intense staining of
      small bodies close to the lumen of seminiferous tubules of spermatogenic stage
      VII and VIII as well as of spermatocytes. Methyl green-pyronin and propidium
      iodide staining combined with DNase or RNase predigestion showed that the small
      bodies contained RNA, but not DNA and double fluorescence staining showed that
      polyamines (PAs) colocalized with RNA in the bodies. Electron microscopy
      confirmed the absence of nuclei in the bodies and revealed that PA
      immunoreactivity was associated with ribosomes. These results strongly suggest
      that the small bodies correspond to the residual bodies, and agree with previous
      results showing localization of PAs to ribosomes in neurons and gastrointestinal
      epithelial cells. The accumulation of PAs in residual bodies may reflect a
      termination of their role in spermiogenesis with respect to protein synthesis.

PMID- 17443341
TI  - Adult living donor liver transplantation: living donation of the right liver
      lobe.
AB  - BACKGROUND: Adult living donor liver transplantation (LDLT) has become a routine
      treatment option for patients waiting for liver transplantation. In European and
      North American countries, LDLT for adult recipients is mainly performed with
      right lobe grafts. Indications, when compared to deceased donor liver
      transplantation, are controversial. MATERIALS AND METHODS: In our institution,
      patients suffering from hepatocellular carcinoma in cirrhosis, non-resectable
      hilar cholangiocarcinoma, viral hepatitis associated cirrhosis, as well as
      cholestatic liver and biliary disease are considered good candidates for LDLT.
      RESULTS: In this overview, donor evaluation, graft selection, and the donor
      operation with special regard to operative techniques and strategies are
      discussed. For visualization, a 5-min video sequence of the standard donor
      operation as performed in our institution is attached. CONCLUSION: Given the
      ongoing shortage of donor organs, adult LDLT has become a routine treatment
      option for patients waiting for liver transplantation. The associated inevitable
      risk for the healthy donor, however, remains ethically controversial.

PMID- 17443342
TI  - Possible involvement of genes on the Q chromosome of Nicotiana tabacum in
      expression of hybrid lethality and programmed cell death during interspecific
      hybridization to Nicotiana debneyi.
AB  - Hybrid seedlings from the cross between Nicotiana tabacum, an allotetraploid
      composed of S and T subgenomes, and N. debneyi die at the cotyledonary stage.
      This lethality involves programmed cell death (PCD). We carried out reciprocal
      crosses between the two progenitors of N. tabacum, N. sylvestris and N.
      tomentosiformis, and N. debneyi to reveal whether only the S subgenome in N.
      tabacum is related to hybrid lethality. Hybrid seedlings from reciprocal crosses
      between N. sylvestris and N. debneyi showed lethal characteristics identical to
      those from the cross between N. tabacum and N. debneyi. Conversely, hybrid
      seedlings from reciprocal crosses between N. tomentosiformis and N. debneyi were
      viable. Furthermore, hallmarks of PCD were observed in hybrid seedlings from the
      cross N. debneyi x N. sylvestris, but not in hybrid seedlings from the cross N.
      debneyi x N. tomentosiformis. We also carried out crosses between monosomic lines
      of N. tabacum lacking the Q chromosome and N. debneyi. Using Q-chromosome
      specific DNA markers, hybrid seedlings were divided into two groups, hybrids
      possessing the Q chromosome and hybrids lacking the Q chromosome. Hybrids
      possessing the Q chromosome died with characteristics of PCD. However, hybrids
      lacking the Q chromosome were viable and PCD did not occur. From these results,
      we concluded that the Q chromosome belonging to the S subgenome of N. tabacum
      encodes gene(s) leading to hybrid lethality in the cross N. tabacum x N. debneyi.

PMID- 17443343
TI  - Overexpression of a Panax ginseng tonoplast aquaporin alters salt tolerance,
      drought tolerance and cold acclimation ability in transgenic Arabidopsis plants.
AB  - Water movement across cellular membranes is regulated largely by a family of
      water channel proteins called aquaporins (AQPs). Since several abiotic stresses
      such as, drought, salinity and freezing, manifest themselves via altering water
      status of plant cells and are linked by the fact that they all result in cellular
      dehydration, we overexpressed an AQP (tonoplast intrinsic protein) from Panax
      ginseng, PgTIP1, in transgenic Arabidopsis thaliana plants to test its role in
      plant's response to drought, salinity and cold acclimation (induced freezing
      tolerance). Under favorable conditions, PgTIP1 overexpression significantly
      increased plant growth as determined by the biomass production, and leaf and root
      morphology. PgTIP1 overexpression had beneficial effect on salt-stress tolerance
      as indicated by superior growth status and seed germination of transgenic plants
      under salt stress; shoots of salt-stressed transgenic plants also accumulated
      greater amounts of Na(+) compared to wild-type plants. Whereas PgTIP1
      overexpression diminished the water-deficit tolerance of plants grown in shallow
      (10 cm deep) pots, the transgenic plants were significantly more tolerant to
      water stress when grown in 45 cm deep pots. The rationale for this contrasting
      response, apparently, comes from the differences in the root morphology and leaf
      water channel activity (speed of dehydration/rehydration) between the transgenic
      and wild-type plants. Plants overexpressed with PgTIP1 exhibited lower (relative
      to wild-type control) cold acclimation ability; however, this response was
      independent of cold-regulated gene expression. Our results demonstrate a
      significant function of PgTIP1 in growth and development of plant cells, and
      suggest that the water movement across tonoplast (via AQP) represents a rate
      limiting factor for plant vigor under favorable growth conditions and also
      significantly affect responses of plant to drought, salt and cold stresses.

PMID- 17443344
TI  - Inherited renal tubular dysgenesis: the first patients surviving the neonatal
      period.
AB  - Renal tubular dysgenesis (RTD) is a clinical disorder either acquired during
      fetal development or inherited as an autosomal recessive condition. Inherited RTD
      is caused by mutations in the genes encoding the components of the renin
      angiotensin system angiotensinogen, renin, angiotensin-converting enzyme and
      angiotensin II receptor type 1. Inherited RTD is characterized by early onset
      oligohydramnios, skull ossification defects, preterm birth and neonatal pulmonary
      and renal failure. The histological hallmark is the absence or poor development
      of proximal tubules. So far, all patients died either in utero or shortly after
      birth. We report the first patients with inherited RTD surviving the neonatal
      period and still being alive. Genetic and functional analysis of the renin
      angiotensin system contributes to the diagnosis of RTD. In conclusion, the
      clinical diagnosis of inherited RTD is easily missed after birth without renal
      biopsy or information on affected family members. Genetic and functional analysis
      of the renin-angiotensin system contributes to correct diagnosis.

PMID- 17443345
TI  - Intracranial aneurysm associated with chronic mucocutaneous candidiasis.
AB  - Chronic mucocutaneous candidiasis (CMC) is a syndrome characterised by immune
      deficiency, often presenting familial dominant inheritance and association with
      autoimmune endocrinopathies. We report on a patient with CMC who died at 5 years
      of age of a brain haemorrhage following the rupture of a basilar-artery aneurysm.
      Candida hyphae in the basilar artery were found at autopsy. A common immunologic
      abnormality in CMC is the failure of patient's T-lymphocytes to produce
      cytokines, which are essential for expression of cell-mediated immunity to
      Candida. Therefore, long-term treatment is mandatory.

PMID- 17443347
TI  - Thyroid involvement in Langerhans cell histiocytosis: a report of two cases and
      review of the literature.
AB  - Langerhans cell histiocytosis (LCH) is a disorder with unclear etiology and
      pathogenesis characterized by abnormal clonal proliferation and accumulation of
      antigen presenting Langerhans' cells at various tissues and organs. Almost all
      organs or systems may be involved, and the prognosis depends on the involved
      sites and the presence of organ dysfunction. Thyroid tissue is a rarely affected
      site in children, and without histopathological evaluation it may be difficult to
      distinguish from other thyroid disorders because of the similar physical
      examination, laboratory and imaging findings. Here we report on two patients with
      histopathologically proven thyroid involvement of LCH. Additionally, the
      differential diagnosis of diffusely enlarged or multinodular thyroid glands in
      children is discussed, and a review of the literature of thyroid involvement in
      LCH is given. In the differential diagnosis of enlarged thyroid glands,
      especially in the presence of other endocrinological manifestations, LCH must be
      taken into consideration.

PMID- 17443348
TI  - Unilateral bloody nipple discharge in a two-month-old male.
AB  - Bloody nipple discharge is a rare but distressing finding in neonates and
      infants. We report on a 2-month-old boy with unilateral bloody nipple discharge.
      Ultrasound examination revealed dilated mammary ducts. This benign phenomenon is
      most likely to be caused by mammary ductal ectasia. Invasive investigations or
      surgery should be avoided in neonates or infants with bloody nipple discharge
      unless the discharge is unilateral, spontaneous, persistent and accompanied with
      a palpable mass. Otherwise only serial clinical follow-up is recommended until
      spontaneous resolution.

PMID- 17443349
TI  - Virus-induced gene silencing of 14-3-3 genes abrogates dark repression of nitrate
      reductase activity in Nicotiana benthamiana.
AB  - In order to study the effect of repression of 14-3-3 genes on actual activity of
      the nitrate reductase (NR) in Nicotiana benthamiana leaves, Nb14-3-3a gene was
      silenced by virus-induced gene silencing (VIGS) method using potato virus X
      (PVX). Expression of Nb14-3-3a as well as Nb14-3-3b genes was altogether
      repressed in the leaves of PVX-14-3a-infected plants. Furthermore, two
      dimensional gel electrophoresis and immunoblot analysis with anti-14-3-3
      antiserum suggested that the expressions of Nb14-3-3a and Nb14-3-3b proteins are
      accordingly repressed in PVX-14-3a-infected plants. It is well known that binding
      of 14-3-3 proteins to phosphorylated NR leads to substantial decrease in NR
      activity of leaves under darkness. Therefore, we studied the changes in NR
      activity in response to light/dark transitions in the leaves of PVX-14-3a
      infected plants. NR activation state was kept at a high level under darkness in
      PVX-14-3a-infected plants, but not in PVX-green fluorescent protein (GFP)
      infected and control plants. This result suggests that Nb14-3-3a and/or Nb14-3-3b
      proteins are indeed involved in the inactivation of NR activity under darkness in
      N. benthamiana.

PMID- 17443351
TI  - Hyperalgesia in response to traumatic occlusion and GFAP expression in rat
      parabrachial [correction of parabranchial] nucleus: modulation with
      fluorocitrate.
AB  - We have examined, by immunocytochemical methods and nociceptive behavior
      assessment in rats, whether astrocytes in the parabrachial nucleus (PBN) are
      involved in the regulation of traumatic occlusion. The expression of glial
      fibrillary acidic protein (GFAP) in PBN of ipsilateral and contralateral sides
      was up-regulated 4 h after occlusal changes in molars, reached peak levels at 24
      h, and was then gradually down-regulated. PBN astrocytes activated by traumatic
      occlusion were found to have enlarged cell bodies and thickened processes within
      8 h. An inhibitor of glia metabolism (FCA, fluorocitrate) reduced astrocyte
      activation and significantly attenuated the development of pain hypersensitivity
      in this model. The results suggested that the GFAP-immunoreactive astrocytes in
      PBN within the bridge of Varolius were activated by traumatic occlusion, and that
      they were involved in the transmission and modulation of nociceptive information
      in the central nervous system. However, although astrocytes in PBN are thus
      probably involved in causing post-occlusal hyperalgesia, we have not been able to
      exclude that astrocytes at other locations also contribute to this effect.

PMID- 17443350
TI  - In vivo functional characterization of the Saccharomyces cerevisiae 60S
      biogenesis GTPase Nog1.
AB  - The Saccharomyces cerevisiae Nog1 GTPase is critical for assembly of the large
      ribosomal subunit. Mutations in conserved residues in the GTP-binding pocket
      cause defects in cell growth and 60S ribosome assembly but mutant proteins retain
      their ability to associate with the pre-60S. Association of Nog1 with the pre-60S
      is independent of guanine nucleotide added to cell extracts. Thus, it appears
      that nucleotide occupancy does not substantially affect Nog1 association with pre
      60S particles. Somewhat surprisingly, neither of the conserved threonines in the
      G2 motif of the GTPase domain is essential for Nog1 function. Neither the steady
      state rRNA levels nor the protein composition (as determined by isobaric labeling
      and identification by mass spectrometry of peptides) of the pre-60S particles in
      the nog1P176V mutant are grossly perturbed, although levels of four proteins
      (Nog1, Nop2, Nop15, and Tif6) are modestly reduced in pre-60S particles isolated
      from the mutant. Deletion analysis revealed that the C-terminal 168 amino acids
      are not required for function; however, the N-terminal 126 amino acids are
      required. Optimal association with pre-60S particles requires sequences between
      amino acids 347-456. Several conserved charge-to-alanine substitutions outside
      the GTPase domain display modest growth phenotypes indicating that these residues
      are not critical for function.

PMID- 17443352
TI  - Human dental follicle cells acquire cementoblast features under stimulation by
      BMP-2/-7 and enamel matrix derivatives (EMD) in vitro.
AB  - The dental follicle (DF) surrounding the developing tooth germ is an
      ectomesenchymal tissue composed of various cell populations derived from the
      cranial neural crest. Human dental follicle cells (HDFC) are believed to contain
      precursor cells for cementoblasts, periodontal ligament cells, and osteoblasts.
      Bone morphogenetic proteins (BMPs) produced by Hertwig's epithelial root sheath
      or present in enamel matrix derivatives (EMD) seem to be involved in the control
      of DF cell differentiation, but their precise function remains largely unknown.
      We report the immunolocalization of STRO-1 (a marker of multipotential
      mesenchymal progenitor cells) and BMP receptors (BMPR) in DF in vivo. In culture,
      HDFC co-express STRO-1/BMPR and exhibit multilineage properties. Incubation with
      rhBMP-2 and rhBMP-7 or EMD for 24 h increases the expression of BMP-2 and BMP-7
      by HDFC. Long-term stimulation of these cells by rhBMP-2 and/or rhBMP-7 or EMD
      significantly increases alkaline phosphatase activity (AP) and mineralization.
      Expression of cementum attachment protein (CAP) and cementum protein-23 (CP-23),
      two putative cementoblast markers, has been detected in EMD-stimulated whole DF
      and in cultured HDFC stimulated with EMD or BMP-2 and BMP-7. RhNoggin, a BMP
      antagonist, abolishes AP activity, mineralization, and CAP/CP-23 expression in
      HDFC cultures and the expression of BMP-2 and BMP-7 induced by EMD.
      Phosphorylation of Smad-1 and MAPK is stimulated by EMD or rhBMP-2. However,
      rhNoggin blocks only Smad-1 phosphorylation under these conditions. Thus, EMD may
      activate HDFC toward the cementoblastic phenotype, an effect mainly (but not
      exclusively) involving both exogenous and endogenous BMP-dependent pathways.

PMID- 17443353
TI  - Kinetic characterization of enhanced lipase activity on oil bodies.
AB  - Enzyme access, kinetic behavior, and protein-protein interactions are critical
      for explaining reaction of the metabolites contained within the myriad
      compartments of biological systems. To explore these relationships, the reaction
      kinetics of oil bodies versus oil emulsions as substrates for lipolytic reactions
      were measured. The initial rate of hydrolysis for the oil body system was
      comparatively very low due to a brief latency period. However, the complete
      activation of the lipase at the interface resulted in an enzyme-membrane complex
      that was catalytically enhanced 3-15-fold over the emulsion system for substrate
      concentrations in the measured range of approximately 1-5.5 mM. This disparity is
      explained by the availability of substrate to the enzyme active site (defined as
      the availability parameter "A") which varies between the two substrates by 40
      fold. A simple hyperbolic kinetic mechanism is proposed with Km replaced by the
      parameter, A, to account for this phenomenon, leading to a maximum rate of
      approximately 1450 IU/ mg protein. The interaction is verified through separation
      of the enzyme-membrane complex which shows nearly double the activity towards an
      emulsified soybean oil substrate (activity ratio of 5:3) when compared to the
      native enzyme.

PMID- 17443354
TI  - Spatial structure and diversity of woody plants and ectomycorrhizal fungus
      sporocarps in a natural subtropical forest.
AB  - Spatial patterns of ectomycorrhizal fungi, ectomycorrhizal plants, and non
      ectomycorrhizal plants were investigated in a natural subtropical forest using
      second-order analysis. The results of spatial pattern analysis showed that the
      degree of clumping of woody plants and ectomycorrhizal sporocarps were
      correlated. There was a significantly positive correlation of relative
      aggregation indices between ectomycorrhizal fungi and both non-ectomycorrhizal
      trees and ectomycorrhizal saplings. Correlations between percentage of
      ectomycorrhizal trees and sporocarp occurrence of ectomycorrhizal fungi and
      between diversities of woody plants and ectomycorrhizal fungi were distance
      dependent or scale-related. A significantly high percentage of ectomycorrhizal
      trees was found only at relatively short distance from ectomycorrhizal fungal
      sporocarps, and significantly positive correlation of the diversity between woody
      plants and ectomycorrhizal fungi was found only at relative long distance, which
      implied that ectomycorrhizal sporocarps prefer ectomycorrhizal-tree-dominant
      micro-sites at near distances and at relatively large scales, diverse
      ectomycorrhizal sporocarps could be found in woodlands with high diversity of
      woody plants. Important factors affecting the spatial distribution, occurrence,
      and diversity of ectomycorrhizal fungi include spatial pattern of ectomycorrhizal
      plants and non-ectomycorrhizal plants, percentage of ectomycorrhizal plants, and
      plant diversity in a natural forest.

PMID- 17443355
TI  - Relative numerosity discrimination by chimpanzees (Pan troglodytes): evidence for
      approximate numerical representations.
AB  - Two adult chimpanzees were trained on a relative "numerosity" discrimination
      task. In each trial, two arrays containing different numbers of red dots were
      presented on a CRT monitor. The subjects were required to choose the array
      containing the larger number of dots. In Experiment 1, using numerosities between
      1 and 8, 28 different pairs were presented repeatedly, and accuracy scores were
      analyzed to explore which cues the chimpanzee subjects utilized to perform the
      task. Multiple regression analyses revealed that the subjects' performance was
      (1) not simply controlled by the "numerical" difference between arrays, but that
      it was (2) best described by Fechner's Law-that is accuracy increased linearly
      with the logarithmic value of the numerical difference between arrays divided by
      the number in the larger of the two arrays. This relationship was maintained when
      using much larger numerosities (Experiment 3). In Experiment 2, the chimpanzees
      were tested on the effects of total area and density by manipulating dot size and
      presentation area. The results revealed that these factors clearly affected the
      subjects' performance but that they could not alone explain the results,
      suggesting that the chimpanzees did use relative numerosity difference as a
      discriminative cue.

PMID- 17443356
TI  - Aspergillus infection of implantable cardioverter-defibrillators and pacemakers:
      case report and literature review.
AB  - Presented here is a case of implantable-cardioverter-defibrillator infection
      caused by Aspergillus flavus and a review of 14 previously reported Aspergillus
      infections of pacemakers or implantable cardioverter-defibrillators. Among all 15
      cases, fever was the most common presenting feature (11 patients). Three patients
      presented with generator-pocket inflammation. Transthoracic echocardiography was
      performed on eight of 13 patients with endocarditis, revealing vegetations in
      only one. Transesophageal echocardiography demonstrated the presence of
      vegetations in all eight of the patients on whom it was performed (p < 0.01).
      Death was due to the Aspergillus infection in five cases. Patients who presented
      with unexplained fever had a higher mortality rate (60%) than patients with other
      clinical presentations (20%, p = 0.166).

PMID- 17443357
TI  - Proof of concept percutaneous treatment system to enable fast and finely
      controlled ablation of biological tissue.
AB  - A prototype system has been developed for producing controllable ablation of
      spherical lesions with a diameter of up to 2 cm. The system is based on a solid
      state energy source operating in the super high frequency (SHF is defined as
      being a frequency of between 3 and 30 GHz) region of the electromagnetic
      spectrum. Results obtained from preliminary tissue testing, performed on morbid
      tissue samples prepared in a laboratory environment, show repeatability in terms
      of shape and size of ablation, and demonstrate the ability to produce controlled
      ablation in morbid liver and kidney models.

PMID- 17443358
TI  - Deposition of free cholesterol in the blood vessels of patients with coronary
      artery disease: a possible novel mechanism for atherogenesis.
AB  - A cholesterol-rich nanoemulsion (LDE) that mimics the composition of low-density
      lipoprotein (LDL) acquires apoE in the plasma and is taken-up by the cells by LDL
      receptors. In this study, to verify whether free cholesterol (FC) and the
      cholesteryl ester (CE) components of LDL are taken-up differently by the vessels.
      LDE labeled with (3)H-cholesterol and (14)C-cholesteryl oleate was injected into
      20 coronary artery disease patients 24 h before a scheduled myocardial coronary
      artery bypass grafting. The plasma kinetics of both radiolabels was determined
      from plasma samples collected over 24 h, and fragments of vessels discarded
      during surgery were collected and analyzed for radioactivity. LDE FC was removed
      faster than CE. The radioactive counting of LDE CE was greater than that of LDE
      FC in the blood, but the uptake of FC was markedly greater than that of CE in all
      fragments: fivefold greater in the aorta (p = 0.04), fourfold greater in the
      internal thoracic artery (p = 0.03), tenfold greater in the saphenous vein (p =
      0.01) and threefold in the radial artery (p = 0.05). In conclusion, the greater
      removal from plasma of FC compared with CE and the remarkably greater vessel
      tissue uptake of FC compared with CE suggests that, in the plasma, FC dissociates
      from the nanoemulsion particles and precipitates in the vessels. Considering LDE
      as an artificial nanoemulsion model for LDL, our results suggest that
      dissociation of FC from lipoprotein particles and deposition in the vessel wall
      may play a role as an independent mechanism in atherogenesis.

PMID- 17443359
TI  - Renal cell carcinoma presenting with paraneoplastic hypercalcemic coma: a case
      report and review of the literature.
AB  - We report a case of a 62-year-old woman with renal cell carcinoma (RCC)
      presenting with a hypercalcemia-induced coma. A laboratory evaluation indicated
      nonparathyroid-mediated hypercalcemia with an initial serum calcium level of 18.6
      mg/dL. Our patient's parathyroid hormone (PTH)-related peptide level was
      undetectable. Initial imaging was negative, but PET scan identified a mass in the
      upper pole of the left kidney. Our patient underwent partial nephrectomy, and the
      mass was identified as RCC on final pathology. After surgery, her hypercalcemia
      resolved and PTH returned to normal limits. This case report describes a patient
      with RCC with the unusual presentation of hypercalcemic coma. We review the
      differential diagnosis of malignant hypercalcemia and the evaluation of
      hypercalcemia occurring with RCC. This case illustrates the need to carefully
      review and interpret all available data, especially when conventional testing in
      the work-up of hypercalcemia is unrevealing.

PMID- 17443360
TI  - Effects of paying physicians based on their relative performance for quality.
AB  - BACKGROUND: Studies examining the effectiveness of pay-for-performance programs
      to improve quality of care primarily have been confined to bonus-type
      arrangements that reward providers for performance above a predetermined
      threshold. No studies to date have evaluated programs placing providers at
      financial risk for performance relative to other participants in the program.
      OBJECTIVE: The objective of the study is to evaluate the impact of an incentive
      program conferring limited financial risk to primary care physicians.
      PARTICIPANTS: There were 334 participating primary care physicians in Rochester,
      New York. DESIGN: The design of the study is a retrospective cohort study using
      pre/post analysis. MEASUREMENTS: The measurements adhere to 4 diabetes
      performance measures between 1999 and 2004. RESULTS: While absolute performance
      levels increased across all measures immediately following implementation, there
      was no difference between the post- and pre-intervention trends indicating that
      the overall increase in performance was largely a result of secular trends.
      However, there was evidence of a modest 1-time improvement in physician adherence
      for eye examination that appeared attributable to the incentive program. For this
      measure, physicians improved their adherence rate on average by 7 percentage
      points in the year after implementation of the program. CONCLUSIONS: This study
      demonstrates a modest effect in improving provider adherence to quality standards
      for a single measure of diabetes care during the early phase of a pay-for
      performance program that placed physicians under limited financial risk. Further
      research is needed to determine the most effective incentive structures for
      achieving substantial gains in quality of care.

PMID- 17443361
TI  - Recognition of depression in older medical inpatients.
AB  - BACKGROUND: Studies of recognition of depression in older (aged 65 or more)
      medical inpatients show low rates of recognition of depression by attending
      physicians. However, few studies have compared different measures of recognition
      of depression. OBJECTIVES: (1) To compare the validity of four indicators of
      recognition of depression and a global measure of recognition against a diagnosis
      of depression and (2) to explore the effect of patient characteristics on
      recognition of depression. METHODS: In a cohort of 264 medical inpatients 65
      years and older (115 with major or minor depression, 78 with no depression),
      sensitivities, specificities, and diagnostic odds ratios (DOR) of 4 indicators of
      recognition (symptoms, diagnosis, treatment, and referral) and a global measure
      of recognition (any of the 4 indicators) were calculated. The associations
      between patient characteristics (age, sex, history of depression, antidepressant
      use before admission, severity of depression, comorbidity, duration of
      hospitalization, disability, and hospital of admission) and recognition were
      explored using multiple logistic regression. RESULTS: Less than half of the
      depressed patients were recognized. The indicator with the highest sensitivity
      was treatment (27.8%, 95% confidence interval [CI] 20.0-37.0), whereas the
      indicator with the best specificity was diagnosis (96.6%, 95% CI 91.9-98.7). The
      unadjusted DOR of global recognition was 2.6 (95% CI 1.5, 4.4). Less comorbidity,
      more severe depression symptoms, a history of depression, longer hospital stay,
      and antidepressant use before admission were significantly associated with better
      global recognition. CONCLUSION: Recognition of depression in elderly medical
      inpatients depends upon the indicator of recognition used.

PMID- 17443362
TI  - Why do general practitioners decline training to improve management of medically
      unexplained symptoms?
AB  - BACKGROUND: General practitioners' (GPs) communication with patients presenting
      medically unexplained symptoms (MUS) has the potential to somatize patients'
      problems and intensify dependence on medical care. Several reports indicate that
      GPs have negative attitudes about patients with MUS. If these attitudes deter
      participation in training or other methods to improve communication,
      practitioners who most need help will not receive it. OBJECTIVE: To identify how
      GPs' attitudes to patients with MUS might inhibit their participation with
      training to improve management. DESIGN: Qualitative study. PARTICIPANTS: GPs (N =
      33) who had declined or accepted training in reattribution techniques in the
      context of a research trial. APPROACH: GPs were interviewed and their accounts
      analysed qualitatively. RESULTS: Although attitudes that devalued patients with
      MUS were common in practitioners who had declined training, these coexisted, in
      the same practitioners, with evidence of intuitive and elaborate psychological
      work with these patients. However, these practitioners devalued their
      psychological skills. GPs who had accepted training also described working
      psychologically with MUS but devalued neither patients with MUS nor their own
      psychological skills. CONCLUSIONS: GPs' attitudes that suggested disengagement
      from patients with MUS belied their pursuit of psychological objectives. We
      therefore suggest that, whereas negative attitudes to patients have previously
      been regarded as the main barrier to involvement in measures to improve patient
      management, GPs devaluing of their own psychological skills with these patients
      may be more important.

PMID- 17443363
TI  - Living alone, patient sex and mortality after acute myocardial infarction.
AB  - BACKGROUND: Psychosocial factors, including social support, affect outcomes of
      cardiovascular disease, but can be difficult to measure. Whether these factors
      have different effects on mortality post-acute myocardial infarction (AMI) in men
      and women is not clear. OBJECTIVE: To examine the association between living
      alone, a proxy for social support, and mortality postdischarge AMI and to explore
      whether this association is modified by patient sex. DESIGN: Historical cohort
      study. PARTICIPANTS/SETTING: All patients discharged with a primary diagnosis of
      AMI in a major urban center during the 1998-1999 fiscal year. MEASUREMENTS:
      Patients' sociodemographic and clinical characteristics were obtained by
      standardized chart review and linked to vital statistics data through December
      2001. RESULTS: Of 880 patients, 164 (18.6%) were living alone at admission and
      they were significantly more likely to be older and female than those living with
      others. Living alone was independently associated with mortality [adjusted hazard
      ratio (HR) 1.6, 95% confidence interval (CI) 1.0-2.5], but interacted with
      patient sex. Men living alone had the highest mortality risk (adjusted HR 2.0,
      95% CI 1.1-3.7), followed by women living alone (adjusted HR 1.2, 95% CI 0.7
      2.2), men living with others (reference, HR 1.0), and women living with others
      (adjusted HR 0.9, 95% CI 0.5-1.5). CONCLUSIONS: Living alone, an easily measured
      psychosocial factor, is associated with significantly increased longer-term
      mortality for men following AMI. Further prospective studies are needed to
      confirm the usefulness of living alone as a prognostic factor and to identify the
      potentially modifiable mechanisms underlying this increased risk.

PMID- 17443364
TI  - Screening for domestic violence among adult women in the United States.
AB  - BACKGROUND: Domestic violence is a problem frequently encountered in health care
      settings and a risk factor for physical and mental health problems. OBJECTIVE: To
      provide nationally representative estimates of rates of domestic violence
      screening among women, to identify predictors of screening, and to describe
      settings where women are screened. DESIGN AND PARTICIPANTS: We examined 4,821
      women over the age of 18 from the second wave of Healthcare for Communities, a
      nationally representative household telephone survey conducted in 2000-2001.
      MEASUREMENTS: Self-reports concerning whether the respondent was ever asked about
      domestic or family violence by any health care provider. RESULTS: Only 7% (95%
      CI, 6%-8%) of women reported they were ever asked about domestic violence or
      family violence by a health care professional. Of women who were asked about
      abuse, nearly half (46%) were asked in a primary care setting, and 24% were asked
      in a specialty mental health setting. Women with risk factors for domestic
      violence were more likely to report being asked about it by a health care
      professional, but rates were still low. CONCLUSIONS: Self-reported rates of
      screening for domestic violence are low even among women at higher risk for
      abuse. These findings reinforce the importance of developing training and raising
      awareness of domestic violence and its health implications. This is especially
      true in primary care and mental health specialty settings.

PMID- 17443365
TI  - Do doctors vote?
AB  - BACKGROUND: Organizational leaders and scholars have issued calls for the medical
      profession to refocus its efforts on fulfilling the core tenets of
      professionalism. A key element of professionalism is participation in community
      affairs. OBJECTIVE: To measure physician voting rates as an indicator of civic
      participation. DESIGN: Cross-sectional survey of a subgroup of physicians from a
      nationally representative household survey of civilian, noninstitutionalized
      adult citizens. PARTICIPANTS: A total of 350,870 participants in the Current
      Population Survey (CPS) November Voter Supplement from 1996-2002, including 1,274
      physicians and 1,886 lawyers; 414,989 participants in the CPS survey from 1976
      1982, including 2,033 health professionals. MEASUREMENTS: Multivariate logistic
      regression models were used to compare adjusted physician voting rates in the
      1996-2002 congressional and presidential elections with those of lawyers and the
      general population and to compare voting rates of health professionals in 1996
      2002 with those in 1976-1992. RESULTS: After multivariate adjustment for
      characteristics known to be associated with voting rates, physicians were less
      likely to vote than the general population in 1998 (odds ratio 0.76; 95%
      confidence interval [CI] 0.59-0.99), 2000 (odds ratio 0.64; 95% CI 0.44-0.93),
      and 2002 (odds ratio 0.62; 95% CI 0.48-0.80) but not 1996 (odds ratio 0.83; 95%
      CI 0.59-1.17). Lawyers voted at higher rates than the general population and
      doctors in all four elections (P < .001). The pooled adjusted odds ratio for
      physician voting across the four elections was 0.70 (CI 0.61-0.81). No
      substantial changes in voting rates for health professionals were observed
      between 1976-1982 and 1996-2002. CONCLUSIONS: Physicians have lower adjusted
      voting rates than lawyers and the general population, suggesting reduced civic
      participation.

PMID- 17443366
TI  - A randomized trial of a physical conditioning program to enhance the driving
      performance of older persons.
AB  - BACKGROUND: As the number of older drivers increases, concern has been raised
      about the potential safety implications. Flexibility, coordination, and speed of
      movement have been associated with older drivers' on road performance. OBJECTIVE:
      To determine whether a multicomponent physical conditioning program targeted to
      axial and extremity flexibility, coordination, and speed of movement could
      improve driving performance among older drivers. DESIGN: Randomized controlled
      trial with blinded assignment and end point assessment. Participants randomized
      to intervention underwent graduated exercises; controls received home,
      environment safety modules. PARTICIPANTS: Drivers, 178, age > or = 70 years with
      physical, but without substantial visual (acuity 20/40 or better) or cognitive
      (Mini Mental State Examination score > or =24) impairments were recruited from
      clinics and community sources. MEASUREMENTS: On-road driving performance assessed
      by experienced evaluators in dual-brake equipped vehicle in urban, residential,
      and highway traffic. Performance rated three ways: (1) 36-item scale evaluating
      driving maneuvers and traffic situations; (2) evaluator's overall rating; and (3)
      critical errors committed. Driving performance reassessed at 3 months by
      evaluator blinded to treatment group. RESULTS: Least squares mean change in road
      test scores at 3 months compared to baseline was 2.43 points higher in
      intervention than control participants (P = .03). Intervention drivers committed
      37% fewer critical errors (P = .08); there were no significant differences in
      evaluator's overall ratings (P = .29). No injuries were reported, and complaints
      of pain were rare. CONCLUSIONS: This safe, well-tolerated intervention maintained
      driving performance, while controls declined during the study period. Having
      interventions that can maintain or enhance driving performance may allow
      clinician-patient discussions about driving to adopt a more positive tone, rather
      than focusing on driving limitation or cessation.

PMID- 17443367
TI  - Are good intentions good enough? Informed consent without trained interpreters.
AB  - OBJECTIVE: To examine the informed consent process when trained language
      interpreters are unavailable. BACKGROUND: Ensuring sufficient patient
      understanding for informed consent is especially challenging for patients with
      Limited English Proficiency (LEP). While US law requires provision of competent
      translation for LEP patients, such services are commonly unavailable. DESIGN AND
      PARTICIPANTS: Qualitative data was collected in 8 prenatal genetics clinics in
      Texas, including interviews and observations with 16 clinicians, and 30 Latina
      patients. Using content analysis techniques, we examined whether the basic
      criteria for informed consent (voluntariness, discussion of alternatives,
      adequate information, and competence) were evident for each of these patients,
      contrasting LEP patients with patients not needing an interpreter. We present
      case examples of difficulties related to each of these criteria, and compare
      informed consent scores for consultations requiring interpretation and those
      which did not. RESULTS: We describe multiple communication problems related to
      the use of untrained interpreters, or reliance on clinicians' own limited
      Spanish. These LEP patients appear to be consistently disadvantaged in each of
      the criteria we examined, and informed consent scores were notably lower for
      consultations which occurred across a language barrier. CONCLUSIONS: In the
      absence of adequate Spanish interpretation, it was uncertain whether these LEP
      patients were provided the quality and content of information needed to assure
      that they are genuinely informed. We offer some low-cost practice suggestions
      that might mitigate these problems, and improve the quality of language
      interpretation, which is essential to assuring informed choice in health care for
      LEP patients.

PMID- 17443368
TI  - What are the essential elements to enable patient participation in medical
      decision making?
AB  - BACKGROUND: Patient participation in shared decision making (SDM) results in
      increased patient knowledge, adherence, and improved outcomes. Despite the
      benefits of the SDM model, many patients do not attain the level of participation
      they desire. OBJECTIVE: To gain a more complete understanding of the essential
      elements, or the prerequisites, critical to active patient participation in
      medical decision making from the patient's perspective. DESIGN: Qualitative
      study. SETTING: Individual, in-depth patient interviews were conducted until
      thematic saturation was reached. Two analysts independently read the transcripts
      and jointly developed a list of codes. PATIENTS: Twenty-six consecutive subjects
      drawn from community dwelling subjects undergoing bone density measurements.
      MEASUREMENTS: Respondents' experiences and beliefs related to patient
      participation in SDM. RESULTS: Five elements were repeatedly described by
      respondents as being essential to enable patient participation in medical
      decision making: (1) patient knowledge, (2) explicit encouragement of patient
      participation by physicians, (3) appreciation of the patient's
      responsibility/rights to play an active role in decision making, (4) awareness of
      choice, and (5) time. LIMITATIONS: The generalizability of the results is limited
      by the homogeneity of the study sample. CONCLUSIONS: Our findings have important
      clinical implications and suggest that several needs must be met before patients
      can become active participants in decisions related to their health care. These
      needs include ensuring that patients (1) appreciate that there is uncertainty in
      medicine and "buy in" to the importance of active patient participation in
      decisions related to their health care, (2) understand the trade-offs related to
      available options, and (3) have the opportunity to discuss these options with
      their physician to arrive at a decision concordant with their values.

PMID- 17443369
TI  - Group visits: promoting adherence to diabetes guidelines.
AB  - BACKGROUND: Current diabetes management guidelines offer blueprints for
      providers, yet type 2 diabetes control is often poor in disadvantaged
      populations. The group visit is a new treatment modality originating in managed
      care for efficient service delivery to patients with chronic health problems.
      Group visits offer promise for delivering care to diabetic patients, as visits
      are lengthier and can be more frequent, more organized, and more educational.
      OBJECTIVE: To evaluate the effect of group visits on clinical outcomes,
      concordance with 10 American Diabetes Association (ADA) guidelines [American
      Diabetes Association, Diabetes Care, 28:S4-36, 2004] and 3 United States
      Preventive Services Task Force (USPSTF) cancer screens [U.S. Preventive Services
      Task Force, http://www.ahrq.gov/clinic/uspstf/resource.htm, 2003]. RESEARCH
      DESIGN AND METHODS: A 12-month randomized controlled trial of 186 diabetic
      patients comparing care in group visits with care in the traditional patient
      physician dyad. Clinical outcomes (HbA1c, blood pressure [BP], lipid profiles)
      were assessed at 6 and 12 months and quality of care measures (adherence to 10
      ADA guidelines and 3 USPSTF cancer screens) at 12 months. RESULTS: At both
      measurement points, HbA1c, BP, and lipid levels did not differ significantly for
      patients attending group visits versus those in usual care. At 12 months,
      however, patients receiving care in group visits exhibited greater concordance
      with ADA process-of-care indicators (p < .0001) and higher screening rates for
      cancers of the breast (80 vs. 68%, p = .006) and cervix (80 vs 68%, p = .019).
      CONCLUSIONS: Group visits can improve the quality of care for diabetic patients,
      but modifications to the content and style of group visits may be necessary to
      achieve improved clinical outcomes.

PMID- 17443370
TI  - The role of medical education in reducing health care disparities: the first ten
      years of the UCLA/Drew Medical Education Program.
AB  - BACKGROUND: The University of California, Los Angeles (UCLA)/Charles R. Drew
      University Medical Education Program was developed to train physicians for
      practice in underserved areas. The UCLA/Drew Medical Education Program students
      receive basic science instruction at UCLA and complete their required clinical
      rotations in South Los Angeles, an impoverished urban community. We have
      previously shown that, in comparison to their UCLA counterparts, students in the
      Drew program had greater odds of maintaining their commitment to medically
      disadvantaged populations over the course of medical education. OBJECTIVE: To
      examine the independent association of graduation from the UCLA/Drew program with
      subsequent choice of physician practice location. We hypothesized that
      participation in the UCLA/Drew program predicts future practice in medically
      disadvantaged areas, controlling for student demographics such as race/ethnicity
      and gender, indicators of socioeconomic status, and specialty choice. DESIGN:
      Retrospective cohort study. PARTICIPANTS: Graduates (1,071) of the UCLA School of
      Medicine and the UCLA/Drew Medical Education Program from 1985-1995, practicing
      in California in 2003 based on the address listed in the American Medical
      Association (AMA) Physician Masterfile. MEASUREMENTS: Physician address was
      geocoded to a California Medical Service Study Area (MSSA). A medically
      disadvantaged community was defined as meeting any one of the following criteria:
      (a) federally designated HPSA or MUA; (b) rural area; (c) high minority area; or
      (d) high poverty area. RESULTS: Fifty-three percent of UCLA/Drew graduates are
      located in medically disadvantaged areas, in contrast to 26.1% of UCLA graduates.
      In multivariate analyses, underrepresented minority race/ethnicity (OR: 1.57; 95%
      CI: 1.10-2.25) and participation in the Drew program (OR: 2.47; 95% CI: 1.59
      3.83) were independent predictors of future practice in disadvantaged areas.
      CONCLUSIONS: Physicians who graduated from the UCLA/Drew Medical Education
      Program have higher odds of practicing in underserved areas than those who
      completed the traditional UCLA curriculum, even after controlling for other
      factors such as race/ethnicity. The association between participation in the
      UCLA/Drew Medical Education Program and physician practice location suggests that
      medical education programs may reinforce student goals to practice in
      disadvantaged communities.

PMID- 17443371
TI  - Stress from uncertainty from graduation to retirement--a population-based study
      of Swiss physicians.
AB  - BACKGROUND: Uncertainty shapes many decisions made by physicians everyday.
      Uncertainty and physicians' inability to handle it may result in substandard care
      and unexplained variations in patterns of care. OBJECTIVE: To describe socio
      demographic and professional characteristics of reactions to uncertainty among
      physicians from all specialties, including physicians in training. DESIGN: Cross
      sectional postal survey. PARTICIPANT: All physicians practicing in Geneva,
      Switzerland (n = 1,994). MEASUREMENT: Reaction to medical care uncertainty was
      measured with the Anxiety Due to Uncertainty and Concern About Bad Outcomes
      scales. The questionnaire also included items about professional characteristics
      and work-related satisfaction scales. RESULTS: After the first mailing and two
      reminders, 1,184 physicians responded to the survey. In univariate analysis,
      women, junior physicians, surgical specialists, generalist physicians, and
      physicians with lower workloads had higher scores in both scales. In multivariate
      models, sex, medical specialty, and workload remained significantly associated
      with both scales, whereas clinical experience remained associated only with
      concern about bad outcomes. Higher levels of anxiety due to uncertainty were
      associated with lower scores of work-related satisfaction, while higher levels of
      concern about bad outcomes were associated with lower satisfaction scores for
      patient care, personal rewards, professional relations, and general satisfaction,
      but not for work-related burden or satisfaction with income-prestige. The
      negative effect of anxiety due to uncertainty on work-related satisfaction was
      more important for physicians in training. CONCLUSION: Physicians' reactions to
      uncertainty in medical care were associated with several dimensions of work
      related satisfaction. Physicians in training experienced the greatest impact of
      anxiety due to uncertainty on their work-related satisfaction. Incorporating
      strategies to deal with uncertainty into residency training may be useful.

PMID- 17443372
TI  - What's in a name? Use of brand versus generic drug names in United States
      outpatient practice.
AB  - BACKGROUND: The use of brand rather than generic names for medications can
      increase health care costs. However, little is known at a national level about
      how often physicians refer to drugs using their brand or generic names.
      OBJECTIVE: To evaluate how often physicians refer to drugs using brand or generic
      terminology. DESIGN AND PARTICIPANTS: We used data from the 2003 National
      Ambulatory Medical Care Survey (NAMCS), a nationally representative survey of
      25,288 community-based outpatient visits in the United States. After each visit,
      patient medications were recorded on a survey encounter form by the treating
      physician or transcribed from office notes. MEASUREMENTS: Our main outcome
      measure was the frequency with which medications were recorded on the encounter
      form using their brand or generic names. RESULTS: For 20 commonly used drugs, the
      median frequency of brand name use was 98% (interquartile range, 81-100%). Among
      12 medications with no generic competition at the time of the survey, the median
      frequency of brand name use was 100% (range 92-100%). Among 8 medications with
      generic competition at the time of the survey ("multisource" drugs), the median
      frequency of brand name use was 79% (range 0-98%; P < .001 for difference between
      drugs with and without generic competition). CONCLUSIONS: Physicians refer to
      most medications by their brand names, including drugs with generic formulations.
      This may lead to higher health care costs by promoting the use of brand-name
      products when generic alternatives are available.

PMID- 17443373
TI  - Associations of patient health-related problem solving with disease control,
      emergency department visits, and hospitalizations in HIV and diabetes clinic
      samples.
AB  - BACKGROUND: Patient problem solving and decision making are recognized as
      essential to effective self-management across multiple chronic diseases. However,
      a health-related problem-solving instrument that demonstrates sensitivity to
      disease control parameters in multiple diseases has not been established.
      OBJECTIVES: To determine, in two disease samples, internal consistency and
      associations with disease control of the Health Problem-Solving Scale (HPSS), a
      50-item measure with 7 subscales assessing effective and ineffective problem
      solving approaches, learning from past experiences, and motivation/orientation.
      DESIGN: Cross-sectional study. PARTICIPANTS: Outpatients from university
      affiliated medical center HIV (N = 111) and diabetes mellitus (DM, N = 78)
      clinics. MEASUREMENTS: HPSS, CD4, hemoglobin A1c (HbA1c), and number of
      hospitalizations in the previous year and Emergency Department (ED) visits in the
      previous 6 months. RESULTS: Administration time for the HPSS ranged from 5 to 10
      minutes. Cronbach's alpha for the total HPSS was 0.86 and 0.89 for HIV and DM,
      respectively. Higher total scores (better problem solving) were associated with
      higher CD4 and fewer hospitalizations in HIV and lower HbA1c and fewer ED visits
      in DM. Health Problem-Solving Scale subscales representing negative problem
      solving approaches were consistently associated with more hospitalizations (HIV,
      DM) and ED visits (DM). CONCLUSIONS: The HPSS may identify problem-solving
      difficulties with disease self-management and assess effectiveness of
      interventions targeting patient decision making in self-care.

PMID- 17443374
TI  - A ten-month program in curriculum development for medical educators: 16 years of
      experience.
AB  - BACKGROUND: Despite increased demand for new curricula in medical education, most
      academic medical centers have few faculty with training in curriculum
      development. OBJECTIVE: To describe and evaluate a longitudinal mentored faculty
      development program in curriculum development. DESIGN: A 10-month curriculum
      development program operating one half-day per week of each academic year from
      1987 through 2003. The program was designed to provide participants with the
      knowledge, attitudes, skills, and experience to design, implement, evaluate, and
      disseminate curricula in medical education using a 6-step model. PARTICIPANTS:
      One-hundred thirty-eight faculty and fellows from Johns Hopkins and other
      institutions and 63 matched nonparticipants. MEASUREMENTS: Pre- and post-surveys
      from participants and nonparticipants assessed skills in curriculum development,
      implementation, and evaluation, as well as enjoyment in curriculum development
      and evaluation. Participants rated program quality, educational methods, and
      facilitation in a post-program survey. RESULTS: Sixty-four curricula were
      produced addressing gaps in undergraduate, graduate, or postgraduate medical
      education. At least 54 curricula (84%) were implemented. Participant self
      reported skills in curricular development, implementation, and evaluation
      improved from baseline (p < .0001), whereas no improvement occurred in the
      comparison group. In multivariable analyses, participants rated their skills and
      enjoyment at the end of the program significantly higher than nonparticipants
      (all p < .05). Eighty percent of participants felt that they would use the 6-step
      model again, and 80% would recommend the program highly to others. CONCLUSIONS:
      This model for training in curriculum development has long-term sustainability
      and is associated with participant satisfaction, improvement in self-rated
      skills, and implementation of curricula on important topics.

PMID- 17443375
TI  - Comparison of hospital costs and length of stay for community internists,
      hospitalists, and academicians.
AB  - BACKGROUND: The model of inpatient medical management has evolved toward
      Hospitalists because of greater cost efficiency compared to traditional practice.
      The optimal model of inpatient care is not known. OBJECTIVE: To compare three
      models of inpatient Internal Medicine (traditional private practice Internists,
      private Hospitalist Internists, and Academic Internists with resident teams) for
      cost efficiency and quality at a community teaching hospital. DESIGN: Single
      institution retrospective cohort study. MEASUREMENTS AND MAIN RESULTS:
      Measurements were hospital cost, length of stay (LOS), mortality, and 30-day
      readmission rate adjusted for severity, demographics, and case mix. Academic
      Internist teams had 30% lower cost and 40% lower LOS compared to traditional
      private Internists and 24% lower cost and 30% lower LOS compared to private
      Hospitalists. Hospital mortality was equivalent for all groups. Academic teams
      had 2.3-2.6% more 30-day readmissions than the other groups. CONCLUSIONS:
      Academic teams compare favorably to private Hospitalists and traditional
      Internists for hospital cost efficiency and quality.

PMID- 17443376
TI  - Characteristics of nondisabled older patients developing new disability
      associated with medical illnesses and hospitalization.
AB  - OBJECTIVE: To identify demographic, clinical, and biological characteristics of
      older nondisabled patients who develop new disability in basic activities of
      daily living (BADL) during medical illnesses requiring hospitalization. DESIGN:
      Longitudinal observational study. SETTING: Geriatric and Internal Medicine acute
      care units. PARTICIPANTS: Data are from 1,686 patients aged 65 and older who
      independent in BADL 2 weeks before hospital admission, enrolled in the 1998
      survey of the Italian Group of Pharmacoepidemiology in the Elderly Study.
      MEASUREMENTS: Study outcome was new BADL disability at time of hospital
      discharge. Sociodemographic, functional status, and clinical characteristics were
      collected at hospital admission; acute and chronic conditions were classified
      according to the International Classification of Disease, ninth revision; fasting
      blood samples were obtained and processed with standard methods. RESULTS: At the
      time of hospital discharge 113 patients (6.7%) presented new BADL disability.
      Functional decline was strongly related to patients' age and preadmission
      instrumental activities of daily living status. In a multivariate analysis, older
      age, nursing home residency, low body mass index, elevated erythrocyte
      sedimentation rate, acute stroke, high level of comorbidity expressed as
      Cumulative Illness Rating Scale score, polypharmacotherapy, cognitive decline,
      and history of fall in the previous year were independent and significant
      predictors of BADL disability. CONCLUSION: Several factors might contribute to
      loss of physical independence in hospitalized older persons. Preexisting
      conditions associated with the frailty syndrome, including physical and cognitive
      function, comorbidity, body composition, and inflammatory markers, characterize
      patients at high risk of functional decline.

PMID- 17443377
TI  - Breast cancer presenting as unilateral arm edema.
AB  - CONTEXT: Symptomatic arm lymphedema as the presenting symptom of invasive breast
      carcinoma is a rare occurrence. DESIGN: We report a case of invasive breast
      cancer presenting with unilateral arm swelling. The patient was initially thought
      to have venous thrombosis. A thorough physical examination and a mammogram
      revealed the presence of breast cancer and associated subclinical axillary
      lymphadenopathy. CONCLUSION: Failure to recognize this presentation can lead to
      misdiagnosis or a significant delay in diagnosis and treatment.

PMID- 17443378
TI  - A shot in the dark: failing to recognize the link between physical and mental
      illness.
AB  - A 74-year-old widowed white man with chronic rheumatoid arthritis presented with
      nausea and weight loss. He was diagnosed with failure to thrive and admitted for
      hydration. Misoprostol was determined to be the etiology of his symptoms and he
      was discharged home. Three days later, he killed himself with a gunshot to the
      head. Clinicians often fail to recognize those at high risk for suicide. Suicidal
      risk is increased in both psychiatric and physical illness, and particularly when
      both are present. Psychiatric illness, particularly depression, often underlies
      chronic medical illness. The purpose of this case report is to remind health care
      providers of the strong association between depression and chronic medical
      illness, and to consider this in all patients, including those who present solely
      with physical symptoms. Recognizing this association and screening for it, as
      recommended by the U.S. Preventive Services Task Force, may prevent the
      unnecessary tragedy of suicide.

PMID- 17443379
TI  - Acute Kawasaki disease: not just for kids.
AB  - Kawasaki Disease is a small-to-medium-vessel vasculitis that preferentially
      affects children. Kawasaki Disease can occur in adults, but the presentation may
      differ from that observed in children. Typical findings in both adults and
      children include fever, conjunctivitis, pharyngitis, and skin erythema
      progressing to a desquamating rash on the palms and soles. Adults more frequently
      present with cervical adenopathy (93% of adults vs. 15% of children), hepatitis
      (65% vs. 10%), and arthralgia (61% vs. 24-38%). In contrast, adults are less
      frequently affected by meningitis (10% vs. 34%), thrombocytosis (55% vs. 100%),
      and coronary artery aneurysms (5% vs. 18-25%). We report a case of acute Kawasaki
      Disease in a 24-year-old man who presented with rash, fever, and arthritis. He
      was successfully treated with high-dose aspirin and intravenous immunoglobulin
      (IVIG). Our case highlights the importance of considering Kawasaki Disease in
      adults presenting with symptoms commonly encountered in a general medical
      practice.

PMID- 17443380
TI  - Classification and diagnosis of patients with medically unexplained symptoms.
AB  - Patients with medically unexplained symptoms (MUS) have little or no demonstrable
      disease explanation for the symptoms, and comorbid psychiatric disorders are
      frequent. Although common, costly, distressed, and often receiving ill-advised
      testing and treatments, most MUS patients go unrecognized, which precludes
      effective treatment. To enhance recognition, we present an emerging perspective
      that envisions a unitary classification for the entire spectrum of MUS where this
      diagnosis comprises severity, duration, and comorbidity. We then present a
      specific approach for making the diagnosis at each level of severity. Although
      our disease-based diagnosis system dictates excluding organic disease to diagnose
      MUS, much exclusion can occur clinically without recourse to laboratory or
      consultative evaluation because the majority of patients are mild. Only the less
      common, "difficult" patients with moderate and severe MUS require investigation
      to exclude organic diseases. By explicitly diagnosing and labeling all severity
      levels of MUS, we propose that this diagnostic approach cannot only facilitate
      effective treatment but also reduce the cost and morbidity from unnecessary
      interventions.

PMID- 17443381
TI  - What does 'respect' mean? Exploring the moral obligation of health professionals
      to respect patients.
AB  - Respect is frequently invoked as an integral aspect of ethics and professionalism
      in medicine, yet it is often unclear what respect means in this setting. While we
      recognize that there are many reasonable ways to think about and use the term
      'respect', in this paper, we develop a conception of respect that imposes a
      distinct moral duty on physicians. We are concerned mainly with the idea of
      respect for persons, or more specifically, respect for patients as persons. We
      develop an account of respect as recognition of the unconditional value of
      patients as persons. Such respect involves respecting the autonomy of patients,
      but we challenge the idea that respect for autonomy is a complete or self
      sufficient expression of respect for persons. Furthermore, we suggest that the
      type of respect that physicians owe to patients is independent of a patient's
      personal characteristics, and therefore, ought to be accorded equally to all.
      Finally, the respect that we promote has both a cognitive dimension (believing
      that patients have value) and a behavioral dimension (acting in accordance with
      this belief).

PMID- 17443383
TI  - Analyzing the problems in managing patients with medically unexplained symptoms.

PMID- 17443382
TI  - Empathy and patient-physician conflicts.
AB  - Physicians associate empathy with benevolent emotions and with developing a
      shared understanding with patients. While there have been many articles on
      managing "difficult" patients, little attention has been paid to the challenges
      physicians face during conflicts with patients, especially when both parties are
      angry and yet empathy is still needed. This topic is especially important in
      light of recent studies showing that practicing medicine increasingly requires
      physicians to manage their own feelings of anger and frustration. This article
      seeks to describe how physicians can learn to empathize with patients even when
      they are both subject to emotions that lead to interpersonal distancing. Empathy
      is defined as engaged curiosity about another's particular emotional perspective.
      Five specific ways for physicians to foster empathy during conflict are
      described: recognizing one's own emotions, attending to negative emotions over
      time, attuning to patients' verbal and nonverbal emotional messages, and becoming
      receptive to negative feedback. Importantly, physicians who learn to empathize
      with patients during emotionally charged interactions can reduce anger and
      frustration and also increase their therapeutic impact.

PMID- 17443384
TI  - Temperature dependence of steady-state and presteady-state kinetics of a type IIb
      Na+/P i cotransporter.
AB  - The temperature dependence of the transport kinetics of flounder Na(+)-coupled
      inorganic phosphate (P(i)) cotransporters (NaPi-IIb) expressed in Xenopus oocytes
      was investigated using radiotracer and electrophysiological assays. (32)P(i)
      uptake was strongly temperature-dependent and decreased by approximately 80% at a
      temperature change from 25 degrees C to 5 degrees C. The corresponding activation
      energy (E (a)) was approximately 14 kcal mol(-1) for the cotransport mode. The
      temperature dependence of the cotransport and leak modes was determined from
      electrogenic responses to 1 mM P(i) and phosphonoformic acid (PFA), respectively,
      under voltage clamp. The magnitude of the P(i)- and PFA-induced changes in
      holding current decreased with temperature. E (a) at -100 mV for the cotransport
      and leak modes was approximately 16 kcal mol(-1) and approximately 11 kcal mol(
      1), respectively, which suggested that the leak is mediated by a carrier, rather
      than a channel, mechanism. Moreover, E (a) for cotransport was voltage
      independent, suggesting that a major conformational change in the transport cycle
      is electroneutral. To identify partial reactions that confer temperature
      dependence, we acquired presteady-state currents at different temperatures with 0
      mM P(i) over a range of external Na(+). The relaxation time constants increased,
      and the peak time constant shifted toward more positive potentials with
      decreasing temperature. Likewise, there was a depolarizing shift of the charge
      distribution, whereas the total available charge and apparent valency predicted
      from single Boltzmann fits were temperature-independent. These effects were
      explained by an increased temperature sensitivity of the Na(+)-debinding rate
      compared with the other voltage-dependent rate constants.

PMID- 17443385
TI  - Ca2+-induced phase separation in the membrane of palmitate-containing liposomes
      and its possible relation to membrane permeabilization.
AB  - A Ca(2+)-induced phase separation of palmitic acid (PA) in the membrane of
      azolectin unilamellar liposomes has been demonstrated with the fluorescent
      membrane probe nonyl acridine orange (NAO). It has been shown that NAO, whose
      fluorescence in liposomal membranes is quenched in a concentration-dependent way,
      can be used to monitor changes in the volume of lipid phase. The incorporation of
      PA into NAO-labeled liposomes increased fluorescence corresponding to the
      expansion of membrane. After subsequent addition of Ca(2+), fluorescence
      decreased, which indicated separation of PA/Ca(2+) complexes into distinct
      membrane domains. The Ca(2+)-induced phase separation of PA was further studied
      in relation to membrane permeabilization caused by Ca(2+) in the PA-containing
      liposomes. A supposition was made that the mechanism of PA/Ca(2+)-induced
      membrane permeabilization relates to the initial stage of Ca(2+)-induced phase
      separation of PA and can be considered as formation of fast-tightening lipid
      pores due to chemotropic phase transition in the lipid bilayer.

PMID- 17443386
TI  - Evolution of hyperactive, repetitive antifreeze proteins in beetles.
AB  - Some organisms that experience subzero temperatures, such as insects, fish,
      bacteria, and plants, synthesize antifreeze proteins (AFPs) that adsorb to
      surfaces of nascent ice crystals and inhibit their growth. Although some AFPs are
      globular and nonrepetitive, the majority are repetitive in both sequence and
      structure. In addition, they are frequently encoded by tandemly arrayed,
      multigene families. AFP isoforms from the mealworm beetle, Tenebrio molitor, are
      extremely potent and inhibit ice growth at temperatures below -5 degrees C. They
      contain a 12-amino acid repeat with the sequence TCTxSxxCxxAx, each of which
      makes up one coil of the beta-helix structure. TxT motifs are arrayed to form the
      ice-binding surface in all three known insect AFPs: the homologous AFPs from the
      two beetles, T. molitor and Dendroides canadensis, and the nonhomologous AFP from
      the spruce budworm, Choristoneura fumiferana. In this study, we have obtained the
      cDNA and genomic sequences of additional T. molitor isoforms. They show variation
      in the number of repeats (from 6 to 10) which can largely be explained by
      recombination at various TCT motifs. In addition, phylogenetic comparison of the
      AFPs from the two beetles suggests that gene loss and amplification may have
      occurred after the divergence of these species. In contrast to a previous study
      suggesting that T. molitor genes have undergone positive Darwinian selection
      (selection for heterogeneity), we propose that the higher than expected ratio of
      nonsynonymous-to-synonymous substitutions might result from selection for higher
      AT content in the third codon position.

PMID- 17443388
TI  - Factors affecting successful breast conservation for ductal carcinoma in situ.
AB  - BACKGROUND: Successful breast-conserving therapy in DCIS is restricted by high
      rates of residual disease resulting in the need for radiotherapy and/or re
      excision. This study identifies patients with DCIS who are most at risk of
      compromised margins and of residual disease. METHODS: All patients undergoing
      breast-conserving surgery for DCIS over a 6-year period were included. Method of
      diagnosis, mammographic size, pathological size, DCIS-margin distance and
      residual disease on re-excision were analysed. RESULTS: One hundred and thirty
      five patients underwent initial breast-conserving surgery for DCIS. The
      compromised margin rate was 72%, and the rate of residual disease on re-operation
      was 54%. On univariate analysis, underestimation of pathological size by
      mammography by >1 cm occurred in 40% of those with compromised margins undergoing
      a therapeutic operation compared to only 14% of those with clear margins (P =
      0.02). However, on multivariate analysis only pathological size (P < 0.0001, OR =
      1.0,95% CI 1.037-1.128) and lack of a preoperative diagnosis by core biopsy (P <
      0.0001, OR = 5.3,95% CI 1.859-15.08) were predictive of compromised margins. The
      presence of residual disease on re-excision was associated with increasing
      pathological size (P < 0.0001, OR = 1.085,95% CI 1.038-1.134) and decreasing DCIS
      margin distance (P = 0.03, OR = 6.694,95% CI 1.84-37.855). Twenty-nine percent (n
      = 13/45) of lesions < or =3 cm compared to 84% (n = 27/32) of lesions >3 cm had
      residual disease on re-operation (P < 0.0001). Residual disease was present in
      62% (n = 34/55), 64% (n = 7/11) and 17% (n = 2/12) of patients with DCIS-margin
      distances < or =1, 1-2 and 2-5 mm, respectively. CONCLUSION: Considerable
      underestimation of DCIS extent by mammography occurs in a high proportion of
      patients with compromised margins in breast conservation. Patients at
      particularly high risk of residual disease on re-excision are those with lesions
      >3 cm and those with DCIS-margin distances of < or = 2mm.

PMID- 17443389
TI  - Single-occupancy binding in simple bounded and unbounded systems.
AB  - The number of substrate molecules that can bind to the active site of an enzyme
      at one time is constrained. This paper develops boundary conditions that
      correspond to the constraint of single-occupancy binding. Two simple models of
      substrate molecules diffusing to a single-occupancy site are considered. In the
      interval model, a fixed number of substrate molecules diffuse in a bounded
      domain. In the spherical model, a varying number of molecules diffuse in a domain
      with boundary conditions that model contact with a reservoir containing a large
      number of substrate molecules. When the diffusive time scale is much shorter than
      the time scale for entering the single-occupancy site, the dynamics of binding
      are accurately described by simple approximations.

PMID- 17443390
TI  - Biomechanical modelling of colorectal crypt budding and fission.
AB  - This paper presents a biomechanical model for the small pits, called crypts, that
      line the colon. A continuum approach is adopted, with the crypt epithelium
      modelled as a growing beam attached to the underlying lamina by cell bonds, which
      generate tension within the layer. These cell attachments are assumed to be
      viscoelastic thus allowing for cell progression along the crypt. It is shown that
      any combination of: an increase in net proliferation (i.e. cell production minus
      apoptosis), an enlargement of the proliferative compartment, an increase in the
      strength of the cellular attachment to the underlying lamina, or a change in the
      rate of cell growth or cell bonding may generate buckling of the tissue. These
      changes can all be generated by an activating mutation of the Wnt cascade, which
      is generally accepted to be the first genetic change in colorectal cancer, with
      subsequent deformation, budding, and crypt fission an observed feature of the
      adenomatous crypt.

PMID- 17443391
TI  - A derivative matching approach to moment closure for the stochastic logistic
      model.
AB  - Continuous-time birth-death Markov processes serve as useful models in population
      biology. When the birth-death rates are nonlinear, the time evolution of the
      first n order moments of the population is not closed, in the sense that it
      depends on moments of order higher than n. For analysis purposes, the time
      evolution of the first n order moments is often made to be closed by
      approximating these higher order moments as a nonlinear function of moments up to
      order n, which we refer to as the moment closure function. In this paper, a
      systematic procedure for constructing moment closure functions of arbitrary order
      is presented for the stochastic logistic model. We obtain the moment closure
      function by first assuming a certain separable form for it, and then matching
      time derivatives of the exact (not closed) moment equations with that of the
      approximate (closed) equations for some initial time and set of initial
      conditions. The separable structure ensures that the steady-state solutions for
      the approximate equations are unique, real and positive, while the derivative
      matching guarantees a good approximation, at least locally in time. Explicit
      formulas to construct these moment closure functions for arbitrary order of
      truncation n are provided with higher values of n leading to better
      approximations of the actual moment dynamics. A host of other moment closure
      functions previously proposed in the literature are also investigated. Among
      these we show that only the ones that achieve derivative matching provide a close
      approximation to the exact solution. Moreover, we improve the accuracy of several
      previously proposed moment closure functions by forcing derivative matching.

PMID- 17443392
TI  - Global properties of infectious disease models with nonlinear incidence.
AB  - We consider global properties for the classical SIR, SIRS and SEIR models of
      infectious diseases, including the models with the vertical transmission,
      assuming that the horizontal transmission is governed by an unspecified function
      f(S,I). We construct Lyapunov functions which enable us to find biologically
      realistic conditions sufficient to ensure existence and uniqueness of a globally
      asymptotically stable equilibrium state. This state can be either endemic, or
      infection-free, depending on the value of the basic reproduction number.

PMID- 17443393
TI  - Prey selection, vertical migrations and the impacts of harvesting upon the
      population dynamics of a predator-prey system.
AB  - A model is developed to describe the interaction between a predator and two prey
      types located in different regions. Conditions for stability and persistence are
      analysed. The effects of harvesting the predators are investigated by making the
      predator mortality rate habitat dependent. Results demonstrate that for any given
      set of parameter values there is a value of the intrinsic preference of the
      predator for each prey type at which the system undergoes a Hopf bifurcation.
      Above this critical value the system evolves towards a stable equilibrium,
      whereas below it, stable limit cycles arise by Hopf bifurcations. Simulations
      demonstrate that the presence of demographic stochasticity may destabilise
      oscillatory populations, thereby causing population extinctions. An application
      of the model to the foraging behaviour of North Sea cod is described. It is shown
      that if the preferred prey is more productive, it is likely that the equilibrium
      will be stable, whereas if the less preferred prey is more productive,
      populations are likely to display cycles and in the stochastic case become
      extinct. As cod fishing mortality is increased, the point of bifurcation and
      region of parameter space for which the system is unstable decreases. An
      increased understanding of how cod behave may enable fish stocks to be managed
      more successfully, for example by indicating where marine reserves should be
      placed.

PMID- 17443394
TI  - On a new method to study drastic change in ecosystems.
AB  - We describe a novel method to study drastic change in ecosystems, based on
      generic functions used in the study of phase transitions and related physical
      phenomena. We illustrate its use by applying it to the problem of shallow lake
      eutrophication, and express our results in terms of an interplay between
      phosphorus content in the water column and fluxes of this substance between the
      lake and both its biological community and its surroundings. We contrast our
      solution to this problem with a previous one based on the concept of resilience,
      and on bifurcation analysis of a dynamical equation that also involves phosphorus
      concentration and fluxes. We then suggest a generalized dynamical scheme
      incorporating the generic functions above, that reduces to our original method in
      the stationary condition, and allows in addition dealing with cyclic and chaotic
      regimes, as illustrated through a particular example.

PMID- 17443396
TI  - Transdermal delivery of interferon alpha-2B using microporation and iontophoresis
      in hairless rats.
AB  - PURPOSE: To demonstrate transdermal delivery of interferon alpha-2b (IFNalpha2b)
      in hairless rats through aqueous microchannels (micropores) created in the skin
      and enhanced by iontophoresis. MATERIALS AND METHODS: The Altea Therapeutics
      PassPort System was configured to form an array of micropores (2.0 cm(2); 72
      micropores/cm(2)) on the rat abdomen. The transdermal patch (Iomed TransQ1-GS
      hydrogel) was saturated with an IFNalpha2b solution (600 microg/ml) and applied
      for 4 h. Delivery was evaluated with and without cathodic iontophoresis (0.1
      mA/cm(2)). Intravenous delivery (0.4 microg/100 g body weight) was performed to
      support pharmacokinetic calculations. RESULTS: IFNalpha2b was not delivered
      through intact skin by itself (passive delivery) or during iontophoresis.
      However, passive delivery through micropores was achieved in vivo in rats. A dose
      of 397 +/- 67 ng was delivered over 6 h, with steady state serum concentrations
      reaching a plateau at 1 h post-patch application. These levels dropped rapidly
      after patch removal, and returned to baseline within 2 h of patch removal.
      Iontophoresis-enhanced delivery through micropores resulted in a two-fold
      increase in the dose delivered (722 +/- 169 ng) in the hairless rat. CONCLUSIONS:
      In vivo delivery of IFNalpha2b was demonstrated through micropores created in the
      outer layer of the skin. Iontophoresis enhanced delivery through microporated
      skin in hairless rats.

PMID- 17443395
TI  - Modern biomaterials: a review - bulk properties and implications of surface
      modifications.
AB  - This review concerns the importance of length and time on physicochemical
      interactions between living tissue and biomaterials that occur on implantation.
      The review provides information on material host interactions, materials for
      medical applications and cell surface interactions, and then details the extent
      of knowledge concerning the role(s) that surface chemistry and topography play
      during the first stage of implant integration, namely protein adsorption. The key
      points are illustrated by data from model in vitro studies. Host implant
      interactions begin nanoseconds after first contact and from then on are in a
      state of flux due to protein adsorption, cell adhesion and physical and chemical
      alteration of the implanted material. The many questions concerning the
      conformational form and control of bound proteins and how this may impact on cell
      adhesion in the first instance and later on cell signalling and implant
      integration can be answered by systematic investigations using model materials.
      Only then we will be in a more informed position to design new materials for use
      in the body.

PMID- 17443397
TI  - Parallel monitoring of plasma and intraluminal drug concentrations in man after
      oral administration of fosamprenavir in the fasted and fed state.
AB  - PURPOSE: The purpose of this study was to explore the feasibility of linking the
      pharmacokinetic profile of a drug with its gastrointestinal behavior by
      simultaneously monitoring plasma and intraluminal drug concentrations.
      Fosamprenavir, a phosphate ester prodrug of the poorly water-soluble HIV
      inhibitor amprenavir, was selected as model compound. METHODS: A single tablet of
      fosamprenavir (Telzir) was administered to 5 volunteers in the fasted and fed
      state (simulated by intake of a nutritional drink). Gastric and duodenal fluids
      were aspirated in function of time and characterized with respect to the
      concentration of (fos)amprenavir, inorganic phosphate and pH. In parallel, blood
      samples were collected and analyzed for amprenavir. RESULTS: The observed plasma
      concentration-time profiles suggested a food-induced delay in the absorption of
      amprenavir: in the fed state, mean tmax increased by more than 150 min compared
      to the fasted state. A similar delay was seen in the duodenal appearance of
      fosamprenavir (concentrations in mM-range) and, after dephosphorylation,
      amprenavir (concentrations below 160 microM). This observation could be related
      to the behavior of fosamprenavir in the stomach. In the fasted state, gastric
      dissolution of fosamprenavir started immediately, resulting in a Cmax of 4 +/- 2
      mM after 43 +/- 15 min; however, in the fed state, the fosamprenavir
      concentration remained below 20 microM for the first 90 min after drug intake.
      The postponed gastric dissolution may be attributed to a food-induced delay in
      tablet disintegration. CONCLUSION: For the first time, the pharmacokinetic
      profile of a drug was monitored in parallel with its gastrointestinal
      concentrations. The observed food effect in the plasma concentration-time profile
      of amprenavir after intake of its phosphate ester prodrug could be related to a
      food-induced delay in gastric dissolution of fosamprenavir.

PMID- 17443398
TI  - Ultrasound mediated transdermal insulin delivery in pigs using a lightweight
      transducer.
AB  - PURPOSE: In previous studies, ultrasound mediated transdermal drug delivery has
      shown a promising potential as a method for noninvasive drug administration. For
      prospective future human application, this study was designed to determine the
      feasibility of lightweight cymbal transducer array as a practical device for
      noninvasive transdermal insulin delivery in large pigs. MATERIALS AND METHODS:
      Six Yorkshire pigs (100-140 lbs) were divided into two groups. As the control (n
      = 3), the first group did not receive any ultrasound exposure with the insulin.
      The second group (n = 3) was treated with ultrasound and insulin at 20 kHz with
      an I(sptp) = 100 mW/cm(2) at a 20% duty cycle for 60 min. With the pigs in
      lateral recumbency after anesthesia, the ultrasound transducer with insulin was
      placed on the axillary area of the pig. At the beginning and every 15 min up to
      90 min, the blood glucose level was determined using a glucose monitoring system.
      To compare the results of individual animals, the change of blood glucose level
      was normalized to each animal's initial glucose value at the start of the
      experiment. RESULTS: Although each animal had a different initial glucose level,
      the mean and standard error for the six animals was 146 +/- 13 mg/dl. For the
      control group, the blood glucose level increased to 31 +/- 21 mg/dl compared to
      the initial baseline over the 90 min experiment. However for the ultrasound with
      insulin treated group, the glucose level decreased to -72 +/- 5 mg/dl at 60 min
      (p < 0.05) and continued to decrease to -91 +/- 23 mg/dl in 90 min (p < 0.05).
      CONCLUSION: The results indicate the feasibility of ultrasound mediated
      transdermal insulin delivery using the cymbal transducer array in animal with a
      similar size and weight to a human. Based on these result, the cymbal array has
      potential as a practical ultrasound system for noninvasive transdermal insulin
      delivery for diabetes management.

PMID- 17443400
TI  - Enhancement of insulin transport across primary rat alveolar epithelial cell
      monolayers by endogenous cellular factor(s).
AB  - PURPOSE: To characterize factor(s) contained in apical medium of primary cultured
      rat alveolar epithelial type II cell-like monolayers (RAECM-II) that enhance
      insulin absorption across alveolar epithelial cells. MATERIALS AND METHODS:
      Primary rat alveolar epithelial cell monolayers cultured on Transwells in the
      presence and absence of 10 ng/ml keratinocyte growth factor for 6 days were dosed
      from the apical compartment with radiolabeled insulin in: newborn bovine serum
      containing medium (SM), conditioned medium from apical compartment of rat
      alveolar epithelial type I cell-like monolayers (RAECM-I) (CMI), or conditioned
      medium from apical compartment of RAECM-II (CMII). At the end of 2 h incubation,
      basolateral medium was collected and amounts of transported radiolabeled insulin
      were determined using a gamma counter. In order to determine the molecular size
      range of the enhancing factor(s), CMII was centrifuged in 50 kDa molecular weight
      cut-off Centricon tubes, and both retentate and filtrate were used as separate
      dosing solutions. Heat denaturation and ammonium sulphate precipitation were used
      to determine if the involved factor(s) represent proteins or other smaller
      soluble factors. Transalveolar transport rates of a paracellular marker, (14)C
      mannitol, and fluid-phase marker, horseradish peroxidase, were determined in the
      presence and absence of the factors. Effects of temperature (4, 16 and 37 degrees
      C) on radiolabeled insulin fluxes were also measured. RESULTS: Conditioned medium
      obtained from the apical compartment of RAECM-II, CMII, increased transport of
      insulin across the monolayers when compared to SM or CMI. The enhancing effect of
      CMII was retained in the precipitate following ammonium sulfate treatment and in
      the retentate after Centricon filtration. The enhancing effect of CMII was
      significantly decreased when heated at 80 degrees C for 15 min. CMII did not
      affect the transport of (14)C-mannitol or HRP, while its effect on insulin
      transport was decreased by 87% when temperature was lowered to 4 degrees C from
      37 degrees C. CONCLUSIONS: Conditioned medium from type II cell-like monolayer
      cultures appears to contain protein factor(s) which seem to be involved in
      facilitating active transcellular transport of insulin across primary cultured
      RAECM-II.

PMID- 17443401
TI  - Pharmacophagy of methyl eugenol by males enhances sexual selection of Bactrocera
      carambolae.
AB  - After pharmacophagy of methyl eugenol (ME), males of Bactrocera carambolae
      (Diptera: Tephritidae) produced (E)-coniferyl alcohol (CF) along with its
      endogenously synthesized pheromonal compounds. CF was shown to be released into
      the air by the ME-fed males only during the courtship period at dusk and
      attracted significantly more males and females than the ME-deprived males in wind
      tunnel assays. However, earlier onset of sexual attraction and a higher mating
      success were observed only in the wind tunnel and field cage assays on the third
      day posttreatment of ME. Field cage observations on the male-to-male interaction
      indicated that the ME-deprived males did not exhibit aggregation behavior, but
      that ME feeding promoted aggregation behavior in B. carambolae. Field cage
      observations revealed that the ME-deprived males were not only attracted to the
      ME-fed males, but also appeared to feed on their anal secretions. The secretions
      were subsequently confirmed to contain CF along with endogenously produced
      pheromonal compounds. Results obtained for B. carambolae were compared to those
      previously obtained from its sibling species, Bactrocera dorsalis, and are
      discussed in light of species advancement in fruit fly-plant relationships.

PMID- 17443399
TI  - Cell penetrating peptides: intracellular pathways and pharmaceutical
      perspectives.
AB  - Cell penetrating peptides, generally categorized as amphipathic or cationic
      depending on their sequence, are increasingly drawing attention as a non-invasive
      delivery technology for macromolecules. Delivery of a diverse set of cargo in
      terms of size and nature ranging from small molecules to particulate cargo has
      been attempted using different types of cell penetrating peptides (CPPs) in vitro
      and in vivo. However, the internalization mechanism of CPPs is an unresolved
      issue to date, with dramatic changes in view regarding the involvement of
      endocytosis as a pathway of internalization. A key reason for the lack of
      consensus on the mechanism can be attributed to the methodology in deciphering
      the internalization mechanism. In this review, we highlight some of the
      methodology concerns, focus more on the internalization pathway and also provide
      a novel perspective about the intracellular processing of CPPs, which is a
      crucial aspect to consider when selecting a cell penetrating peptide as a drug
      delivery system. In addition, recent applications of cell penetrating peptides
      for the delivery of small molecules, peptides, proteins, oligonucleotides,
      nanoparticles and liposomes have been reviewed.

PMID- 17443402
TI  - Attentional strategy moderates effects of pain catastrophizing on symptom
      specific physiological responses in chronic low back pain patients.
AB  - In the present study, we examined whether experimentally-manipulated attentional
      strategies moderated relations between pain catastrophizing and symptom-specific
      physiological responses to a cold-pressor task among sixty-eight chronic low back
      patients. Patients completed measures of pain catastrophizing and depression, and
      were randomly assigned to sensory focus, distraction or suppression conditions
      during a cold pressor. Lumbar paraspinal and trapezius EMG, and cardiovascular
      responses to the cold pressor were assessed. Attentional strategies moderated the
      relation between pain catastrophizing and lumbar paraspinal muscle, but not
      trapezius muscle or cardiovascular responses. Only for participants in the
      suppression condition was catastrophizing related significantly to lumbar
      paraspinal muscle responses. Depressed affect did not account for this relation.
      These findings indicate that 'symptom-specific' responses among pain
      catastrophizers with chronic low back depend on how they attend to pain-related
      information. Specifically, it appears that efforts to suppress awareness of pain
      exaggerate muscular responses near the site of injury.

PMID- 17443403
TI  - Recovery attributions: explicit endorsement of biomedical factors and implicit
      dominance of psycho-social factors.
AB  - Two studies assessed lay people's bio-medical and psycho-social attributions for
      recovery, using implicit and explicit methods, and one of them, Study 2, also
      measured individual differences in health locus of control. Participants were
      presented with a vignette of a patient with a severe disease for which chances of
      recovery vary widely, who had high or low levels of medical care and high or low
      psycho-social resources. They estimated his chances to recover from his illness
      (implicit attributions), and then, imagining another patient with the same
      disease, evaluated the relative importance of medical, psycho-social and other
      factors for his chances for recovery (explicit method). Findings show a
      moderation effect by assessment method: the explicit method pointed to dominance
      of biomedical attributions and the implicit method indicated dominance of psycho
      social attributions. In addition, internal health locus of control was positively
      correlated with psycho-social attributions and external health locus of control
      (powerful others and chance) was correlated with biomedical attributions for
      recovery. The findings are discussed in relation to dual-process models of
      reasoning and self-serving defensive processes.

PMID- 17443404
TI  - Assessment and etiology of attention deficit hyperactivity disorder and
      oppositional defiant disorder in boys and girls.
AB  - Attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder
      (ODD) are more common in boys than girls. In this paper, we investigated whether
      the prevalence differences are attributable to measurement bias. In addition, we
      examined sex differences in the genetic and environmental influences on variation
      in these behaviors. Teachers completed the Conners Teacher Rating Scale
      Revised:Short version (CTRS-R:S) in a sample of 800 male and 851 female 7-year
      old Dutch twins. No sex differences in the factor structure of the CTRS-R:S were
      found, implying the absence of measurement bias. The heritabilities for both ADHD
      and ODD were high and were the same in boys and girls. However, partly different
      genes are expressed in boys and girls.

PMID- 17443405
TI  - Streptococcus bovis endophthalmitis: a unique presentation of colon cancer.

PMID- 17443406
TI  - Hepatitis associated with aplastic anemia: do CD8(+) kupffer cells have a role in
      the pathogenesis?

PMID- 17443407
TI  - The association of human immunodeficiency virus infection with spontaneously
      resolved hepatitis C virus infection and level of viremia among injection drug
      users.
AB  - This study aimed to investigate whether HIV and HIV-related factors are
      associated with spontaneously resolved hepatitis C virus (HCV) infection and
      levels of hepatitis C viremia. Among 351 anti-HCV(+) injection drug users, with
      and without HIV infection, multivariate methods were used to evaluate whether HIV
      status and HIV viral load, CD4 T-cell count, and concurrent HIV antiretroviral
      therapy were associated with (1) spontaneously resolved HCV infection and (2) HCV
      RNA levels. In 186 HIV patients, decreased HCV resolution was independently
      associated with Black race and modestly associated with CD4 T-cell count <200
      cells/ml. Among 310 patients with persistent HCV infection, higher HCV RNA levels
      were independently associated with HIV status but not with other HIV-related
      factors. HIV may be associated with persistent HCV infection in patients with low
      CD4 T-cell counts. Moreover, HIV is associated with increased HCV viral load,
      which may attenuate response to HCV antiviral treatment in coinfected patients.

PMID- 17443408
TI  - Hyperamylasemia, reactive plasmacytosis, and immune abnormalities in a patient
      with celiac disease.

PMID- 17443409
TI  - Hepatolithiasis and cholangiocarcinoma in cystic fibrosis: a case series and
      review of the literature.

PMID- 17443410
TI  - Duodenal gastrointestinal stromal tumor adjacent to the minor papilla with
      concomitant pancreatic divisum.

PMID- 17443411
TI  - Mesenteric venulitis: a rare etiology of hematochezia and "colitis" with
      distinctive colon pathology.

PMID- 17443412
TI  - Elevated carbohydrate antigen 19-9 caused by early colon cancer treated with
      endoscopic mucosal resection.

PMID- 17443413
TI  - Adenocarcinoma of the prostate presenting as an obstructing rectal mass.

PMID- 17443414
TI  - Primary squamous cell carcinoma of the stomach that developed with Menetrier's
      disease.

PMID- 17443416
TI  - A systematic review of myeloid leukemias and occupational pesticide exposure.
AB  - OBJECTIVE: To conduct a systematic review and meta-analyses of published studies
      examining the association between myeloid leukemias (ML) and occupational
      pesticide exposure. METHODS: Studies were identified from a MEDLINE search
      through 31 May 2006 and from the reference lists of identified publications.
      Studies were summarized and evaluated for publication bias. Relative risk
      estimates for ML were extracted from 17 cohort and 16 case-control studies
      published between 1979 and 2005. Fixed- or random-effect meta-analysis models
      were used depending on the presence of heterogeneity between studies. Separate
      analyses were conducted after stratification for study design, occupational
      group, ML subtype or gender. RESULTS: The overall meta-rate ratio estimate (meta
      RR) for the cohort studies was 1.21 (95% confidence interval [CI] 0.99-1.48).
      Substantial heterogeneity existed among cohort studies (p=1.064 x 10(-5)), mainly
      reflecting the varying occupational categories examined. The meta-RR was 6.32
      (95% CI: 1.90-21.01) for manufacturing workers and 2.14 (95% CI: 1.39-3.31) for
      pesticide applicators. After stratification of cohort studies by specific ML
      subtype, an increased risk of acute myeloid leukemia (AML) was found (meta-RR:
      1.55; 95% CI: 1.02-2.34). No significant heterogeneity was detected among case
      control studies and an increased risk of chronic myeloid leukemia (CML) was found
      among men (meta-RR: 1.39; 95% CI: 1.03-1.88) and farmers or agricultural workers
      (meta-RR: 1.38; 95% CI: 1.06-1.79). CONCLUSION: The strongest evidence of an
      increased risk of ML comes from manufacturing workers and pesticide applicators.
      Further studies will be needed to correlate reliable exposure data within these
      specific occupational groups with well-defined subtypes of leukemia to refine
      this assessment.

PMID- 17443415
TI  - Fruit and vegetable consumption and lymphoma risk in the European Prospective
      Investigation into Cancer and Nutrition (EPIC).
AB  - INTRODUCTION: Lymphomas are a heterogeneous group of malignant diseases of cells
      of the immune system. The best-established risk factors are related to dys
      regulation of immune function, and evidence suggests that factors such as dietary
      or lifestyle habits may be involved in the etiology. MATERIAL AND METHODS: In the
      European Prospective Investigation into Cancer and Nutrition (EPIC), 849 lymphoma
      cases were identified in a median follow-up period of 6.4 years. Fruit and
      vegetable consumption was estimated from validated dietary questionnaires. Cox
      proportional hazard models were used to examine the association between fruit and
      vegetable intake with the risk of lymphomas overall and subentities. RESULTS:
      There was no overall association between total fruit and vegetable consumption
      and risk of lymphoma [hazard ratio (HR)=0.95, 95% confidence interval (CI) 0.78
      1.15 comparing highest with lowest quartile]. However, the risk of diffuse large
      B-cell lymphomas (DLBCL) tended to be lower in participants with a high intake of
      total vegetables (HR=0.49, 95% CI 0.23-1.02). CONCLUSION: In this large
      prospective study, an inverse associations between fruit and vegetable
      consumption and risk of lymphomas overall could not be confirmed. Associations
      with lymphoma subentities such as DLBCL warrant further investigation.

PMID- 17443417
TI  - Transgene flow to hybrid rice and its male-sterile lines.
AB  - Gene flow from genetically modified (GM) crops to the same species or wild
      relatives is a major concern in risk assessment. Transgenic rice with insect
      and/or disease resistance, herbicide, salt and/or drought tolerance and improved
      quality has been successfully developed. However, data on rice gene flow from
      environmental risk assessment studies are currently insufficient for the large
      scale commercialization of GM rice. We have provided data on the gene flow
      frequency at 17 distances between a GM japonica line containing the bar gene as a
      pollen donor and two indica hybrid rice varieties and four male-sterile (ms)
      lines. The GM line was planted in a 640 m2 in an isolated experimental plot (2.4
      ha), which simulates actual conditions of rice production with pollen
      competition. Results showed that: (1) under parallel plantation at the 0-m zone,
      the transgene flow frequency to the ms lines ranged from 3.145 to 36.116% and was
      significantly higher than that to hybrid rice cultivars (0.037-0.045%). (2) Gene
      flow frequency decreased as the distance increased, with a sharp cutoff point at
      about 1-2 m; (3) The maximum distance of transgene flow was 30-40 m to rice
      cultivars and 40-150 m to ms lines. We believe that these data will be useful for
      the risk assessment and management of transgenic rice lines, especially in Asia
      where 90% of world's rice is produced and hybrid rice varieties are extensively
      used.

PMID- 17443418
TI  - Call for echo-contrast.

PMID- 17443419
TI  - Differential item functioning impact in a modified version of the Roland-Morris
      Disability Questionnaire.
AB  - OBJECTIVE: To evaluate a modified version of the Roland-Morris Disability
      Questionnaire for differential item functioning (DIF) related to several
      covariates. BACKGROUND: DIF occurs in an item when, after controlling for the
      underlying trait measured by the test, the probability of endorsing the item
      varies across groups. METHODS: Secondary data analysis of two studies of
      participants with back pain (total n = 875). We used a hybrid item response
      theory/ logistic regression approach for detecting DIF. We obtained scores that
      accounted for DIF. We evaluated the impact of DIF on individual and group scores,
      and compared scores that ignored or accounted for DIF in terms of the strength of
      association with SF-36 subscale scores. RESULTS: DIF was found in 18/23 items.
      Salient scale-level differential functioning was found related to age, education,
      and employment. Overall 24 participants (3%) had salient scale-level differential
      functioning. Mean scores across demographic groups differed minimally when
      accounting for DIF. The strength of association of scores with SF-36 scores was
      similar for scores that ignored and scores that accounted for DIF. CONCLUSIONS:
      The modified version of the Roland-Morris Disability Questionnaire appears to
      have largely negligible DIF related to the covariates assessed here.

PMID- 17443420
TI  - Differential item functioning and health assessment.
AB  - Establishing measurement equivalence is important because inaccurate assessment
      may lead to incorrect estimates of effects in research, and to suboptimal
      decisions at the individual, clinical level. Examination of differential item
      functioning (DIF) is a method for studying measurement equivalence. An item
      (i.e., one question in a longer scale) exhibits DIF if the item response differs
      across groups (e.g., gender, race), controlling for an estimate of the construct
      being measured. A distinction between applications in health, as contrasted with
      other settings such as educational and aptitude testing, is that there are many
      health-related constructs and multiple measures of each, few of which have
      received much critical evaluation. Discussed in this article are several methods
      for detection of differential item functioning (DIF), including non-parametric
      and parametric methods such as logistic regression, and those based on item
      response theory. Basic definitions and criteria for DIF detection are provided,
      as are steps in performing the analyses. Recommendations are presented and future
      directions discussed.

PMID- 17443422
TI  - [New therapeutic systems of neuroprotectors agents in the treatment of glaucoma].

PMID- 17443423
TI  - [Should we prescribe antioxidant drugs in ARMD patients?].

PMID- 17443424
TI  - [Relationship between standard automated perimetry and HRT, OCT and GDx in
      normal, ocular hypertensive and glaucomatous subjects].
AB  - PURPOSE: To determine the correlations between structural parameters of the optic
      nerve head and the retinal nerve fiber layer (RNFL) obtained by using a
      Heidelberg Retina Tomograph II (HRT II), optic coherence tomography (OCT), and
      laser polarimetry (GDX-VCC) and the perimetric indices of standard automated
      perimetry (SAP) in normal, ocular hypertensive and glaucomatous subjects.
      METHODS: Three hundred and eighty-nine patients were enrolled in the study and
      classified into three separate groups: 43 with normal eyes, 274 with ocular
      hypertensive eyes and 72 with glaucomatous eyes. Subjects were classified
      according to the basal intraocular pressure and the SAP results. Pearson's
      correlation coefficients were calculated between the global perimetric indices,
      mean deviation (MD) and pattern standard deviation (PSD), and structural
      parameters of the RNFL and optic disc obtained by using HRT II, OCT and GDX-VCC
      in the different diagnostic groups. RESULTS: Mild to moderate correlations were
      found between the structural parameters measured by HRT, OCT and GDX and the
      global perimetric indices, in the glaucoma group. Mild or no significant
      correlations were found in the normal and ocular hypertensive groups.
      Correlations were stronger for MD than for PSD. Parameters based on the study of
      the retinal nerve fiber layer showed stronger correlations than those based on
      the study of the optic nerve head. CONCLUSIONS: The relationship between
      structural and functional measurements in glaucoma is weak and therefore the
      results of these ancillary tests should be interpreted together to increase
      diagnostic accuracy.

PMID- 17443425
TI  - [Diabetic retinopathy epidemiology in type II diabetic patients. Effect of the
      changes in the diagnostic criteria and stricter control of the diabetes between
      1993 and 2005 on the incidence of diabetic retinopathy].
AB  - OBJECTIVE: The aim of the study was to compare the results with those of a
      previous study by the same author in 1993 when 741 type II diabetic patients were
      recruited. We determined the prevalence of diabetic retinopathy and the impact of
      the new diagnostic criteria and stricter control of diabetes on the results
      obtained. METHODS: The study sample was obtained by hazard selection of 741 type
      II diabetic patients, from the total diabetic patients visited in the interval
      between January 1 and December 1 in 2005. RESULTS: We observed a decrease in the
      prevalence of diabetic retinopathy between the two studies. In the first study
      the incidence was 39.41% while in the present study it was 27.55%. The diabetic
      macular edema prevalence was similar in both studies (7.15% in the past and 7.90%
      in the present study). There was also a decrease in the number of blind patients
      (11.20% in 1993 and 4.90% in the current study). The number of patients treated
      with laser photocoagulation increased (13.49% in the current study as compared to
      6.20% in the previous study). Statistic analysis revealed the risk factors for
      retinopathy: diabetes mellitus duration, elevated HbA1C levels and the need for
      insulin treatment. CONCLUSIONS: A better control of diabetes mellitus may lead us
      to observe an increase in visual acuity, and a better control of diabetic
      retinopathy. The incidence of diabetic retinopathy certainly decreased between
      the study periods; however the overall incidence of diabetes in the community has
      increased during the last few years, making firm conclusions difficult.

PMID- 17443426
TI  - [Epidemiology of pseudotumor cerebri].
AB  - OBJECTIVE: To determine the epidemiology of pseudotumor cerebri (PTC) as seen in
      patients attending our ophthalmology department. METHODS: The medical records of
      patients diagnosed with PTC in our hospital during a ten-year period (1994 to
      2004) were obtained, with only those patients with PTC diagnosed in our
      ophthalmology department being considered. The following data were reviewed: sex,
      age at diagnosis, body mass index (BMI), opening cerebrospinal fluid (CSF)
      pressure, and the results of CT and MRI. RESULTS: Twenty-nine patients were
      diagnosed with PTC during this time period. Twenty-six were females (89.6%) and 3
      were males (10.4%). The calculated incidence of PTC in our population was 3.2 per
      100.000 persons and 5.1 per 100.000 persons in the general population that attend
      our hospital. CONCLUSION: The incidence of PTC was higher than that previously
      reported.

PMID- 17443427
TI  - [Retinal toxicity of intravitreal doxycycline. A pilot study].
AB  - OBJECTIVE: To assess the retinal toxicity of varying concentrations of
      intravitreally administered doxycycline, a member of tetracycline family.
      METHODS: Fourteen New Zealand albino rabbits, divided into 5 groups, were used
      for this study. The initial concentration of doxycycline (100 mg) was titrated
      using 5% dextrose solution to the following concentrations in a volume of 0.1 ml:
      2000 microg, 1000 microg, 500 microg, 250 microg, 125 microg, and 62.5 microg.
      Each concentration was injected into 2 rabbit eyes. Two control eyes received 0.1
      ml of 5% dextrose solution. All animals were examined before and after injection
      using indirect ophthalmoscopy and slit-lamp biomicroscopy. Electroretinography
      (ERG) was performed on all animals prior to the intravitreal injection and 2
      weeks post-injection. The animals were re-examined at this time by indirect
      ophthalmoscopy and slit-lamp biomicroscopy and were then subjected to euthanasia.
      Their eyes were enucleated and examined using light microscopy. RESULTS: The
      doxycycline injected group exhibited significant decreases in ERG of the eyes
      injected with 2000 microg, 1000 microg, 500 microg, and 250 microg/0.1 ml. No
      significant changes in the ERG were observed following the injection of lesser
      concentration levels. There were no signs of retinal toxicity on slit-lamp
      examination, indirect ophthalmoscopy, or light microscopy in all the eyes
      injected with doxycycline concentrations of 125 microg or lower. CONCLUSIONS:
      Doxycycline injected intravitreally appeared safe at concentrations of 125
      microg/0.1 ml or less in albino rabbits. Intravitreal doxycycline may be
      beneficial, and is an inexpensive alternative drug which could be used in the
      treatment of bacterial endophthalmitis particularly against resistant
      Staphylococcus aureus organisms.

PMID- 17443428
TI  - [Adenocarcinoma with apocrine differentiation of the lacrimal gland].
AB  - CASE REPORT: A 74-year-old male presented with an orbital tumor located in the
      left lacrimal fossa. Ocular examination showed hypotropia, exophthalmos and
      palpebral ptosis. DISCUSSION: Removal of the tumor was performed by a lateral
      orbitotomy. The histopathologic study showed a tumor consistent with an
      adenocarcinoma of the lacrimal gland with apocrine differentiation.

PMID- 17443429
TI  - [Giant cell collagenoma of the bulbar conjunctiva].
AB  - PURPOSE/METHODS: To report a rare case of a tumor in a conjunctival location, a
      giant cell collagenoma. Tissue was stained with hematoxylin-eosin, periodic acid
      Schiff, and Masson's trichromic stain and studied by immunohistochemistry.
      RESULTS/CONCLUSION: The clinical and histopathologic features of conjunctival
      giant cell collagenoma are similar to characteristics of the same tumor occurring
      in other parts of the body. This is the first report of this tumor in the eye.

PMID- 17443430
TI  - [Sclerokeratitis and invasive conjunctival squamous cell carcinoma].
AB  - PURPOSE/METHODS: To describe one case of invasive squamous cell carcinoma of the
      conjunctiva in a 74-year-old woman, who two years previously had presented with a
      lesion which appeared to be an anterior nodular scleritis. RESULTS/CONCLUSIONS:
      An anterior nodular scleritis, which did not respond to therapy, preceded the
      development of a squamous cell carcinoma of the conjunctiva adjacent to it. In
      our patient, the conjunctival squamous cell carcinoma could have masqueraded as a
      scleritis, delaying the correct diagnosis and allowing orbital spread of the
      tumor. A diagnosis of neoplasia must be considered when a scleritis shows an
      atypical appearance or does not respond to the usual therapy.

PMID- 17443431
TI  - [Deposits of perfluoroctane after prolonged use as a post-operative vitreous
      substitute].
AB  - CASE REPORT: We describe a 72-year-old woman with a retinal detachment who
      underwent pars plana vitrectomy (PPV) and intraocular tamponade with a
      combination of silicone oil and perfluoro-n-octane as a postoperative vitreous
      tamponade. Three months later, plaque-like deposits of emulsified perfluoro-n
      octane were visible on the inferior retina. DISCUSSION: Deposits of emulsified
      perfluoro-n-octane, as epiretinal plaques, have not been previously been
      described as adverse reactions following the use of perfluorocarbons in the eye.

PMID- 17443432
TI  - [Optical coherence tomography of retinal pigment epithelial tears].
AB  - CASE REPORTS: Three cases of pigmentary epithelial tears are described in this
      study. One of them was related to previous extrafoveal photocoagulation, whereas
      the other two were idiopathic. Fluorescein angiography (FA) and optical coherence
      tomography (OCT) were performed to confirm the clinical diagnosis. DISCUSSION:
      Few studies using OCT to assess pigmentary retinal epithelial (RPE) tears have
      been published in the world literature. The main findings of our study included
      hyper-reflectant line breaks, choroidal hyper-reflectance due to the lack of RPE
      and RPE double layering where it was folded. Images were frequently associated
      with RPE tears and neurosensorial retinal detachment.

PMID- 17443433
TI  - [The teaching of ophthalmology in Valladolid].

PMID- 17443434
TI  - [Leon Gambetta].

PMID- 17443435
TI  - Stimulatory effect of puerarin on bone formation through activation of PI3K/Akt
      pathway in rat calvaria osteoblasts.
AB  - Puerarin, a natural isoflavonoid found in Chinese Pueraria lobata (Wild.) Ohwi,
      has received increasing attention because of its possible role in the prevention
      of osteoporosis. However, the relationship between puerarin and bone formation
      remains unknown. In the present study, rat osteoblasts isolated from newborn
      Wistar rats were used to investigate the effect of puerarin on osteoblasts, and
      its possible molecular mechanism. Data showed that puerarin caused a significant
      increase in cell viability, alkaline phosphatase (ALP) activity and mineral
      nodules formation in osteoblasts, suggesting that puerarin had a stimulatory
      effect on osteoblastic bone formation. This functional improvement by puerarin
      was accompanied by activation and nuclear translocation of Akt. Furthermore,
      puerarin-stimulated osteoblastic growth, Akt activation and redistribution were
      significantly blocked by the specific PI3K inhibitor, LY294002. These results
      strongly suggested that puerarin stimulated osteoblastic proliferation and Akt
      activation in a PI3K-dependent manner. In summary, puerarin derived from Chinese
      Pueraria lobata (Wild.) Ohwi can promote bone formation in cultured rat
      osteoblasts, which might be mediated by activation of the PI3K/Akt pathway.
      DMEM:Dulbecco's modification of Eagel's medium PBS:phosphate buffered saline
      DMSO:dimethyl sulfoxide EDTA:ethylene diamine tetraacetic acid SDS:sodium dodecyl
      sulfate SDS-PAGE:sodium dodecylsulfate polyacrylamide gel electrophoresis
      FITC:fluorescein isothiocyanate HRP:horseradish peroxidase
      PI3K:phosphatidylinositol 3-kinase.

PMID- 17443436
TI  - Antiplatelet activity of geranylgeraniol isolated from Pterodon pubescens fruit
      oil is mediated by inhibition of cyclooxygenase-1.
AB  - Geranylgeraniol is a natural isoprenoid with anti-inflammatory properties
      extracted from the Pterodon pubescens Benth. fruit oil (PpO). In this work, the
      antiplatelet effect of both PpO and geranylgeraniol is investigated. ADP-,
      thrombin- and arachidonic acid (AA)-induced aggregation in human and rabbit
      platelets showed a prime involvement of PpO and geranylgeraniol in the
      arachidonic acid cascade. The lack of any significant inhibition of platelet
      aggregation induced by U-46 619 and thrombin, associated with PpO and
      geranylgeraniol suppression of prostaglandin E(2) and thromboxane A(2) formation
      demonstrate, for the first time, the involvement of geranylgeraniol in the AA
      metabolisation by inhibiting the cyclooxygenase enzyme.

PMID- 17443437
TI  - [Creative therapy options for patients with dementia--a systematic review].
AB  - The specifics of creative therapies aim at activating the creative potential of
      the patients in the sense of acceptance, orientation and coping with their
      illness "dementia" and at improving their quality of life. Creative therapies in
      the treatment of dementia offer the advantage of working with these patients,
      whose cognition and often also verbal communication skills are affected in a
      nonverbal way. This article presents a systematic review of studies and case
      studies, which could be found on the subject of the implementation of active
      creative therapies "music-, art-, drama- and dance-therapy" within the following
      databases (05/05): Medline, Psyndex Plus, PsychInfo and Cochrane. The search
      terms used were: "Creativ* and therapy and dementia and (stud*)", "Dance therapy
      and dementia", "Music therapy and dementia", "Drama therapy and dementia" and
      "Art therapy and dementia". As a result of this search we found seven
      quantitative evaluated controlled studies, three prae-post comparisons and three
      qualitative evaluated studies which have been finished since 1998. All of these
      studies included groups of at least three participants. Further reviews are
      mentioned in this article. This survey of studies on creative therapies for
      patients with dementia shows positive effects like the improvement of interaction
      skills. The data supplied thus supports the approach of using creative therapies
      in order to help patients accept dementia as their illness and finally to cope
      with it. The methodical approach to the registration of the therapies' effects
      and process-orientated contents of the therapy create a field of tension, leading
      to the request for a further development and validation of instruments, which
      allow the quantitative evaluation of parameters like liveliness, agility and
      interaction skills.

PMID- 17443438
TI  - [Neuropsychiatric bases of the methylphenidate-therapy of the attention
      deficit/hyperactivity disorder (ADHD)].
AB  - High prevalence and high co-morbidity rates with frequently aggravating
      psychosocial problems make the attention-deficit/hyperactivity disorder (ADHD) of
      children, adolescents and adults an important target for research and healthcare.
      Recent findings suggest a dopaminergic fronto-striatal information processing
      deficit in ADHD-patients (executive functions). This review summarizes and
      presents, in the context of recent studies (MRI, f-MRI, PET, SPECT, Mapping
      Genes) the neurobiochemical bases of the methylphenidate-therapy, clinically
      successfully applied since almost one half century by the ADHD. The increased
      striatal dopamine transporter density by the ADHD-methylphenidate-responder is
      reported as a scientifically sound and useful clinical working model.

PMID- 17443439
TI  - [The importance of choline and different serum parameters for the course of the
      anorexia nervosa].
AB  - Malnutrition in anorexia nervosa was simulated in an animal starvation study.
      Female rats aged 11 to 13 weeks received a hypocaloric standard diet or a
      hypocaloric choline reduced diet. Weight reduction lasted for 12 to 20 weeks and
      was between 30 % to 40 % of initial weight. Several animals were refed after
      weight reduction up to 6 to 12 weeks with a standard or a choline enriched diet
      ad libitum. Serum parameters and membrane fluidity of the CNS were measured after
      weight reduction or after refeeding. Weight reduction leads to a significant
      decrease of serum protein, triglycerides (Z = -3.53 resp. -3.42; p < 0.001) and
      an increase of membrane fluidity in the CNS (Z = -2.83; p < 0.001). Long-term
      diet with marked weight reduction and following refeeding causes a catabole
      metabolic situation with significant increase of urea/creatinine-ratio. Choline
      enriched refeeding after diet results in normalization of serum parameters and
      membrane fluidity of the CNS. Choline enrichment leads to a significant increase
      of serum protein (Z = -2.03; p < 0.01). Besides we found a negative correlation
      between serum protein and urea/creatinine-ratio (r (S) = -0.47; p < 0.001; n =
      64). This is possibly caused by a reduced protein catabolism or an increased
      protein anabolism. Furthermore membrane fluidity in the CNS correlates with serum
      protein (r (S) = 0.65; p < 0.001; n = 41) and with serum creatinine levels (r (S)
      = 0.58; p < 0.001; n = 42). We conclude that these serum parameters are potential
      predictors for cell function in the starved brain and consequently for the course
      of anorexia nervosa. We furthermore hypothesize that choline enriched nutrition
      after starvation improves the stabilization of cerebral membranes and the
      metabolic situation in anorexia nervosa.

PMID- 17443440
TI  - [Complex regional pain syndromes: new aspects on pathophysiology and therapy].
AB  - Complex-regional pain syndromes (CRPS), formerly known as Sudeck's dystrophy and
      causalgia, belong to the neuropathic pain syndromes. CRPS may develop following
      fractures, limb trauma or lesions of the peripheral or central (CNS) nervous
      system. Occasionally, CRPS may also develop spontaneously. The clinical picture
      comprises a characteristic clinical triade of symptoms including autonomic
      (disturbances of skin temperature, colour, presence of sweating abnormalities),
      sensory (pain and hyperalgesia) and motor (paresis, tremor, dystonia)
      disturbances. Diagnosis is mainly based on clinical signs. However, additional
      laboratory, neurophysiological and radiological examinations may help to
      corroborate correct diagnosis. Several pathophysiological concepts have been
      proposed to explain the complex symptoms of CRPS: 1, facilitated neurogenic
      inflammation; 2, pathological sympatho-afferent coupling; 3, neuroplastic changes
      within the CNS. Furthermore, there is accumulating evidence that genetic factors
      may predispose for CRPS. Therapy is based on a multidisciplinary approach. Non
      pharmacological approaches include physiotherapy and occupational therapy.
      Pharmacotherapy is based on individual symptoms and includes steroids, free
      radical scavengers, treatment of neuropathic pain, and finally agents interfering
      with bone metabolism (calcitonin, biphosphonates). Sympathetic blocks are useful
      for the treatment of sympathetically maintained pain. Invasive therapeutic
      concepts include implantation of spinal cord stimulators. This review covers new
      aspects of pathophysiology and therapy of CRPS.

PMID- 17443441
TI  - [Dyskinesia in Parkinson's disease--major clinical features, aetiology, therapy].
AB  - Parkinson's disease (PD), a slowly, progressive degenerative disorder of the
      central nervous system, which affects about ten million people world-wide, is
      currently treated symptomatically. Current treatment aim i. e. to balance the
      decreased dopamine turnover in striatal neurons. Chronic exposure to dopaminergic
      agents, however, supports onset of motor complications and dyskinesia in the long
      term. Dyskinesia appear mainly as chorea, athetosis, dystonia, stereotypia,
      ballism or a combination. Sometimes excessive abnormal facial, body and limb
      movements depend on the overall dosage of dopaminergic substitution. This is why
      the main therapy is based on reducing the total dosage of dopaminergic
      substances. Either alternative or additional well-tried substances like
      apomorphine, amantadine or clozapine are used. New possibilities in treatment
      emerge from substances like sarizotan, istradefylline, fipampezol or talampanel.
      Even so disability and reduced quality of life in PD patients and their
      caregivers may exist. This survey describes the major clinical features,
      aetiology and demographics of treatment-associated dyskinesia in PD.

PMID- 17443442
TI  - [Bone density measurement: quantitative ultrasound of the calcaneus and distal
      radius. A comparison with dual spectrum X-ray absorptiometry].
AB  - BACKGROUND AND OBJECTIVE: Quantitative ultrasound (QUS) has been successfully
      used for more than a decade in predicting the risk of osteoporotic fractures.
      However, the "gold standard" in the diagnosis of osteoporosis is dual-energy X
      ray absorptiometry (DXA). The aim of this study was to perform QUS at the
      calcaneus and distal radius, as well as DXA over the lumbar spine and proximal
      femur in women and to compare both QUS results with the DXA ones. PATIENTS AND
      METHODS: 230 postmenopausal Bulgarian women, aged between 42 and 80 years, took
      part in this study. QUS was performed ar the calcaneus and the radius. At the
      calcaneus the "quantitative ultrasound index" (QUI) was used, but at the radius
      the speed of sound (SOS) T-scores (SD's under the mean value for young healthy
      adults) were calculated. RESULTS: The highest accuracy was observed at the radius
      (coefficient of variance 0.59 %), followed by that for the total hip (0.95 %).
      The lowest mean T-scores were found at the lumbar spine (-1.94), followed by the
      calcaneus (-1.85) und radius (-1.74). The correlation coefficients between
      calcaneal QUI and BMD of the lumbar spine and proximal femur were 0,285 and 0.442
      (p=0.059 and 0.001, respectively); the corresponding values for radial SOS were
      0.201 and 0.061 (p=0.019 and 0.513, respectively: no significant difference). T
      scores of -1.0 for the Sahara device and of -0.5 for the Sunlight device
      identified women without spinal osteoporosis with a 90% probability. CONCLUSIONS:
      Women with normal bone density of the proximal femur were better identified using
      transverse QUS at the calcaneus. Both QUS techniques (transverse and axial) are
      well suited for identifying women without osteoporosis of the lumbar spine.

PMID- 17443443
TI  - [Generalized lymphadenitis associated with Hashimoto's thyroiditis].
AB  - HISTORY AND ADMISSION FINDINGS: A 26-year-old Pakistani woman was admitted to
      hospital with fever, nausea and vomiting, abdominal pain and general weakness for
      the previous two weeks, but no diarrhea or constipation. Antibiotic therapy as an
      out-patient had not provided relief. She also had enlarged cervical lymph nodes.
      She reported that she had always been in good health before onset of the
      described symptoms. INVESTIGATIONS: Laboratory tests revealed pancytopenia and a
      decrease in C3 and C4. The ANA titer was positive. The serum was positive for
      preceding infections with EBV, CMV, Chlamydia trachomatis, HHV type 6, and
      toxoplasmosis. There was no evidence of current or previous infections with HIV,
      Bartonella henselae, Treponema pallidum, Listeria, Hantavirus, Leishmania or
      dengue fever. The patient's symptoms were found to be associated with Hashimoto's
      thyroiditis in conjunction with latent hypothyroidism. Abdominal, thoracic and
      cervical CT scan revealed enlarged lymph nodes, up to 2 cm in size, and enlarged
      spleen and liver. THERAPY AND CLINICAL COURSE: Histopathology of a cervical lymph
      node showed features of Kikuchi (Kikuchi-Fujimoto) disease (histiocytic
      necrotizing lymphadenitis). Prednisone administration (2 mg/kg body weight) led
      to the patient's rapid recovery. CONCLUSION: Kikuchi disease should be considered
      in patients with cervical but also general lymphadenopathy, after exclusion of
      other causes. The specific diagnosis is based on biopsy of affected lymph nodes.

PMID- 17443444
TI  - [Mixed connective tissue disease and HELLP syndrome in pregnancy].
AB  - HISTORY AND ADMISSION FINDINGS: A 35-year-old woman (gravida 4, para 3) was known
      to have mixed connective tissue disease (MCTD-Sharp's syndrome) for five years,
      treated with immunosuppressives. She was in the 20 + 4 week of an unwanted
      pregnancy. DIAGNOSIS: On admission she had marked eclampsia with severe
      hypertension (180/130 mmHg), laboratory tests revealing hemolysis, elevated liver
      enzymes and thrombocytopenia, indicating an HELPP syndrome (severe eclampsia with
      hemolysis, elevated liver function and low platelets). TREATMENT AND COURSE: The
      symptoms worsened over a few days, the patient initially having refused
      treatment. The fetus died in utero. After drug-induction of labor the fetus was
      ejected and with further supportive treatment the patient's condition rapidly
      improved. CONCLUSION: This patient developed HELPP syndrome in association with
      MCTD. There is no proof that the collagen disease had a causal or aggravating
      effect on the development of HELPP syndrome.

PMID- 17443445
TI  - [Crohn disease, exacerbated during pregnancy].

PMID- 17443446
TI  - [Molecular basis of common variable immunodeficiency].

PMID- 17443447
TI  - [Indications for UVB-phototherapy].

PMID- 17443448
TI  - [Development of obesity in Germany--prevalence, determinants and perspectives].

PMID- 17443449
TI  - [A plea for more precision of the German language in surgery: a commentary in
      honor of Prof. Dr. Matthias Rothmund's 65(th) birthday].

PMID- 17443450
TI  - [Geriatric psychiatry: from the margins to the center].

PMID- 17443451
TI  - [Is quality of life in dementia patients validly estimable?].
AB  - OBJECTIVE: The measurement of quality of life (QoL) in dementia is a
      methodological challenge because of the patients' cognitive impairment and
      anosognosia. This review gives an overview of the possibilities and
      methodological problems of QoL measurement in dementia patients. METHODS: With
      literature searches conducted in PubMed and Web of Science 12 dementia-specific
      QoL-measures were identified. RESULTS: Most authors agreed that patients with
      mild to moderate dementia themselves can validly and reliably estimate their QoL.
      But with increasing severity of the disease, patient ratings must mostly be
      replaced by proxy ratings. The latter are especially essential in longitudinal
      studies, but are not a satisfying substitute for the patients' perspective. Thus,
      the influence of depression and care-related burden on the proxies' QoL-ratings
      should be controlled. CONCLUSIONS: QoL-instruments, applicable to all stages of
      dementia should be preferred, because longitudinal QoL-measures are more
      meaningful than cross sectional analyses. The patients' perspective should be
      taken into consideration as long as possible, since proxies assess the QoL of
      dementia patients differently from the persons affected.

PMID- 17443452
TI  - [Alterations of time judgement with age].
AB  - OBJECTIVE: Time perception can be divided into two processes: time experience and
      time judgement. Although there have been frequent reports of changes in these two
      processes with increasing age, none of these changes has been demonstrated using
      objective measures. METHODS: We evaluated time judgement by employing time
      estimation, time production, and time reproduction tasks in 33 healthy subjects
      of all age groups. In addition, we used the Trail-Making Test to measure
      attentional performance. RESULTS: For both time estimation and time reproduction,
      we found positive correlations between length of time interval and age
      (overestimation). After we calculated partial correlations controlling for the
      results of the Trail-Making Test, the age-related changes we initially observed
      in the time estimation task disappeared, but the age-related changes seen in the
      time reproduction task remained significant. CONCLUSIONS: Considering the Scalar
      Timing Theory and the Attentional Gate Theory, our findings indicated that age
      related effects on time estimation may be due to attentional factors. In
      contrast, the age-related changes seen in the time reproduction task may be due
      to disturbances in working memory function.

PMID- 17443453
TI  - [Do German World War II victims fulfill PTSD-criteria?].
AB  - OBJECTIVE: Long-term psychiatric consequences of World War II are currently a
      main medical and political topic in Germany. METHODS: This retrospective study
      examined 33 psychogeriatric cases. RESULT: PTSD-criteria following ICD-10 were
      fulfilled in every case. All patients had a delayed subtype of PTSD with a
      latency of 14-60 years between trauma and onset of disorder. No case of chronic
      PTSD was found. In 26 cases a depression was diagnosed. CONCLUSIONS: Long
      latencies for PTSD are a typical feature in psychogeriatrics, possibly due to the
      situation in post-war-Germany probably even more in the Soviet occupied zone, the
      later German Democratic Republic (GDR). In the GDR it was not at all a public
      topic to speak about Russian violence (political taboo). The depressive and
      psychotic comorbidity of psychogeriatric PTSD-patients should be examined more
      specifically in future studies.

PMID- 17443454
TI  - [Gerontopsychiatry in the community--results of a gerontopsychiatric outpatient
      network].
AB  - OBJECTIVE: Evaluation of a three-year pilot project which aims to improve the
      quality of care of gerontopsychiatric patients. The project goal was to expand
      regionally organized outpatient services. METHODS: We examined the profile
      (n=1004) and course (n=790) of patients treated at the Kaufbeuren regional
      Gerontopsychiatric Centre on the basis of sociodemographic, clinical, and care
      requirement variables. RESULTS: There was a diagnostic predominance of dementia
      and depression. During the running time of the pilot project, only 13 % of the
      patients had to be admitted to inpatient care. CONCLUSIONS: The results suggest
      that the quality of gerontopsychiatric care improves through consistent efforts
      that are outpatient-oriented, mobile and multiprofessionally organized.

PMID- 17443455
TI  - [Physicians' competence regarding the early diagnosis of dementia: differences
      between family physicians and primary care neuropsychiatrists in Germany].
AB  - OBJECTIVE: Are there any differences between family physicians (FP) and primary
      care neuropsychiatrists (NP) with regard to their diagnostic competence of early
      dementia? METHODS: Trained interviewers presented written case vignettes to 68 NP
      and 122 FP during a structured interview. The case history described an otherwise
      healthy 70 years old patient complaining about cognitive disturbances suggesting
      incipient dementia. RESULTS: The survey is representative with a high response
      rate (71.8% FP and 67.3% NP). In both physician groups a vascular disease concept
      prevailed although the patient had no vascular risk factors. For primary and
      differential diagnosis NP considered depression more often. Overall only about
      50% of physicians considered Alzheimer dementia. Regarding diagnostic methods the
      NP adhered significantly better to the current guidelines. While 31% of FP would
      apply dementia screening and 12% order neuroimaging, 76% and 74% of the NP
      mentioned these methods, respectively. CONCLUSIONS: There are negligible
      differences between NP and HA with regard to early diagnostic awareness of
      dementia. Vascular concepts prevail. However, both groups differ with regard to
      the diagnostic work-up. An increase of competence seems to be necessary in both
      groups.

PMID- 17443456
TI  - [Screening of cognitive functions and the prediction of incident dementia by
      means of the SIDAM].
AB  - OBJECTIVE: The suitability of the SIDAM (Structured Interview for the Diagnosis
      of Dementia) for the detection of pre-clinical stages of dementia. METHODS:
      Prospective study of a sample of 794 non-demented elderly persons in the age
      bracket from 65 to 85 who were initially being treated in general hospitals. A
      cognitive screening with the SIDAM was performed during their stay in the
      hospital. After discharge the occurrence of dementia was determined in four
      follow-up studies at one-year intervals. RESULTS: During the follow-up, 100 newly
      developed cases of dementia were diagnosed. A lower performance in the SIDAM was
      associated with a significantly higher risk of the development of dementia. In
      comparison with the upper quartile in total SIDAM score the relative risk of a
      dementia amounted to 2.6 (1.0-6.8) for the second quartile, 4.5 (1.9-11.0) for
      the third quartile and 13.3 (5.7-31.1) for the fourth quartile. The highest
      predictive validity was found for memory performance, in particular for free
      delayed recall. CONCLUSIONS: Risk groups for dementia can be identified by the
      use of a brief cognitive screening procedure.

PMID- 17443457
TI  - Viral load in blood is correlated with disease severity of neonatal
      coxsackievirus B3 infection: early diagnosis and predicting disease severity is
      possible in severe neonatal enterovirus infection.
AB  - We conducted a study during an outbreak of coxsackievirus B3 infection in 2005
      and found that viral RNA could be detected in patients' blood specimens soon
      after the onset of fever, and the level of viral RNA was positively correlated
      with disease severity. Timely diagnosis is possible in severe neonatal
      enterovirus infection.

PMID- 17443458
TI  - Overwhelming parasitemia with Plasmodium falciparum infection in a patient
      receiving infliximab therapy for rheumatoid arthritis.
AB  - We describe a 45-year-old woman receiving infliximab therapy for rheumatoid
      arthritis who developed an overwhelming Plasmodium falciparum infection with
      cerebral malaria. Physicians should be aware that patients receiving tumor
      necrosis factor inhibitors, such as infliximab, may be at increased risk of life
      threatening malarial infections.

PMID- 17443459
TI  - Haemophilus ducreyi causing chronic skin ulceration in children visiting Samoa.
AB  - Chancroid is a sexually transmitted infection associated with genital ulceration
      and lymphadenopathy caused by Haemophilus ducreyi. Localized skin infections, in
      the absence of genital lesions, have not been previously reported. We report 3
      cases of lower limb ulceration in children caused by H. ducreyi and postulate
      that H. ducreyi may be a previously unrecognized cause of chronic skin
      ulceration.

PMID- 17443460
TI  - What is tuberculosis surveillance in the European Union telling us?
AB  - BACKGROUND: Today's European Union (EU) encompasses countries with diverse
      patterns of tuberculosis epidemiology. METHODS: We explored national tuberculosis
      data for 1999-2003 reported to the EuroTB surveillance network. We analyzed only
      complete, representative data for drug resistance (from 15 countries) and
      treatment outcomes (from 19 countries). RESULTS: Between 1999 and 2003, overall
      tuberculosis notification rates in the 25 EU countries decreased by 4% each year,
      down to 14 cases per 100,000 population in 2003, but Italy and the United Kingdom
      registered increases because of tuberculosis in immigrants. In 2003, EU countries
      reported 62,743 tuberculosis cases; of these, 76% were in persons who were
      previously untreated, 22% were in persons >64 years old, and 30% were in
      foreigners (the percentage in individual countries ranged from 2% to 75%). In
      Estonia, Latvia, and Lithuania, resistance to isoniazid and rifampicin occurred
      in 15%-23% of cases in which resistance testing was performed, but it was
      uncommon elsewhere (median resistance, 1%). Among previously untreated culture
      positive patients with pulmonary tuberculosis, 76% had successful outcome (the
      percentage in individual countries ranged from 54% to 100%); among these
      patients, the probability of successful outcome diminished with advancing age. Of
      9414 patients with AIDS reported in the EU, 2207 (23%) had tuberculosis as the
      initial defining illness, representing 3% of all tuberculosis cases notified that
      year (the percentage in individual countries ranged from 0% to 10%). The
      prevalence of HIV infection among patients with tuberculosis was highest in
      Portugal (16.1%) and Spain (9.6%), but it increased in Estonia (from 0.1% to
      2.9%) and in Latvia (from 0.5% to 2.3%) between 1999 and 2003. CONCLUSIONS:
      Surveillance data would be more comparable if more countries reported exhaustive
      and representative data. Drug resistance is low in most EU countries other than
      former Soviet states. HIV infection and tuberculosis comorbidity is important in
      certain countries. Prevention and control of tuberculosis in the EU should target
      groups at higher risk of infection or death, including foreigners and the elderly
      population.

PMID- 17443461
TI  - Tuberculosis surveillance: data for decision-making.

PMID- 17443462
TI  - Immunity to pertussis 5 years after booster immunization during adolescence.
AB  - BACKGROUND: We conducted a 5-year follow-up study on the persistence of pertussis
      specific antibody and cell-mediated immunity after booster immunization of
      adolescents aged 11-13 years with a tricomponent acellular pertussis vaccine
      (Boostrix; trials diphtheria-tetanus-acellular pertussis [Tdap]-004/030).
      METHODS: Cellular and humoral immunity to pertussis toxin (PT), filamentous
      hemagglutinin, and pertactin were measured in adolescents (age, 16 years) 5 years
      after booster immunization. Similar investigations were performed for control
      adolescents who had received only diphtheria and tetanus booster vaccination.
      RESULTS: Five years after pertussis booster vaccination, the geometric mean
      concentrations of immunoglobulin G (IgG) elicited by each of the 3 pertussis
      vaccine antigens decreased from 1-month and 3-year postvaccination levels, but
      with the exception of PT IgG, were still higher than the prevaccination levels.
      PT IgG levels were undetectable in 28% of the subjects, but 44% of those subjects
      still tested positive for cell-mediated immunity to PT. Filamentous hemagglutinin
      IgG and pertactin IgG levels were significantly higher in Tdap-boosted
      adolescents than in the control subjects. Antibody concentrations at 1 month
      after vaccination strongly predicted antibody persistence. Cell-mediated immunity
      levels to PT, filamentous hemagglutinin, and pertactin persisted above the
      prebooster levels measured 5 years earlier. CONCLUSIONS: The results of the
      present study of adolescents indicate that the interval between acellular
      pertussis booster immunizations might be extended beyond 5 years.

PMID- 17443463
TI  - Immunity to pertussis.

PMID- 17443464
TI  - Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic
      neuralgia in older adults.
AB  - BACKGROUND: A vaccine to prevent herpes zoster was recently approved by the
      United States Food and Drug Administration. We sought to determine the cost
      effectiveness of this vaccine for different age groups. METHODS: We constructed a
      cost-effectiveness model, based on the Shingles Prevention Study, to compare
      varicella zoster vaccination with usual care for healthy adults aged >60 years.
      Outcomes included cost in 2005 US dollars and quality-adjusted life expectancy.
      Costs and natural history data were drawn from the published literature; vaccine
      efficacy was assumed to persist for 10 years. RESULTS: For the base case
      analysis, compared with usual care, vaccination increased quality-adjusted life
      expectancy by 0.0007-0.0024 quality-adjusted life years per person, depending on
      age at vaccination and sex. These increases came almost exclusively as a result
      of prevention of acute pain associated with herpes zoster and postherpetic
      neuralgia. Vaccination also increased costs by $94-$135 per person, compared with
      no vaccination. The incremental cost-effectiveness ranged from $44,000 per
      quality-adjusted life year saved for a 70-year-old woman to $191,000 per quality
      adjusted life year saved for an 80-year-old man. For the sensitivity analysis,
      the decision was most sensitive to vaccine cost. At a cost of $46 per dose,
      vaccination cost <$50,000 per quality-adjusted life year saved for all adults >60
      years of age. Other variables related to the vaccine (duration, efficacy, and
      adverse effects), postherpetic neuralgia (incidence, duration, and utility),
      herpes zoster (incidence and severity), and the discount rate all affected the
      cost-effectiveness ratio by >20%. CONCLUSIONS: The cost-effectiveness of the
      varicella zoster vaccine varies substantially with patient age and often exceeds
      $100,000 per quality-adjusted life year saved. Age should be considered in
      vaccine recommendations.

PMID- 17443465
TI  - Liposomal amphotericin B as initial therapy for invasive mold infection: a
      randomized trial comparing a high-loading dose regimen with standard dosing
      (AmBiLoad trial).
AB  - BACKGROUND: Treatment of invasive mold infection in immunocompromised patients
      remains challenging. Voriconazole has been shown to have efficacy and survival
      benefits over amphotericin B deoxycholate, but its utility is limited by drug
      interactions. Liposomal amphotericin B achieves maximum plasma levels at a dosage
      of 10 mg/kg per day, but clinical efficacy data for higher doses are lacking.
      METHODS: In a double-blind trial, patients with proven or probable invasive mold
      infection were randomized to receive liposomal amphotericin B at either 3 or 10
      mg/kg per day for 14 days, followed by 3 mg/kg per day. The primary end point was
      favorable (i.e., complete or partial) response at the end of study drug
      treatment. Survival and safety outcomes were also evaluated. RESULTS: Of 201
      patients with confirmed invasive mold infection, 107 received the 3-mg/kg daily
      dose, and 94 received the 10-mg/kg daily dose. Invasive aspergillosis accounted
      for 97% of cases. Hematological malignancies were present in 93% of patients, and
      73% of patients were neutropenic at baseline. A favorable response was achieved
      in 50% and 46% of patients in the 3- and 10-mg/kg groups, respectively
      (difference, 4%; 95% confidence interval, -10% to 18%; P>.05); the respective
      survival rates at 12 weeks were 72% and 59% (difference, 13%; 95% confidence
      interval, -0.2% to 26%; P>.05). Significantly higher rates of nephrotoxicity and
      hypokalemia were seen in the high-dose group. CONCLUSIONS: In highly
      immunocompromised patients, the effectiveness of 3 mg/kg of liposomal
      amphotericin B per day as first-line therapy for invasive aspergillosis is
      demonstrated, with a response rate of 50% and a 12-week survival rate of 72%. The
      regimen of 10 mg/kg per day demonstrated no additional benefit and higher rates
      of nephrotoxicity.

PMID- 17443466
TI  - Trial design for mold-active agents: time to break the mold--aspergillosis in
      neutropenic adults.

PMID- 17443467
TI  - Risk factors, clinical characteristics, and outcome of Nocardia infection in
      organ transplant recipients: a matched case-control study.
AB  - BACKGROUND: Risk factors for Nocardia infection in organ transplant recipients
      have not been formally assessed in the current era of transplantation. METHODS:
      We performed a matched case-control study (1:2 ratio) between January 1995 and
      December 2005. Control subjects were matched for transplant type and timing.
      Univariate matched odds ratios were determined and conditional logistic
      regression was performed to identify independent risk factors. Clinical and
      microbiological characteristics of all case patients were reviewed. RESULTS:
      Among 5126 organ transplant recipients, 35 (0.6%) were identified as having cases
      of Nocardia infection. The highest frequency was among recipients of lung
      transplants (18 [3.5%] of 521 patients), followed by recipients of heart (10
      [2.5%] of 392), intestinal (2 [1.3%] of 155), kidney (3 [0.2%] of 1717), and
      liver (2 [0.1%] of 1840) transplants. In a comparison of case patients with 70
      matched control subjects, receipt of high-dose steroids (odds ratio, 27; 95%
      confidence interval, 3.2-235; P=.003) and cytomegalovirus disease (odds ratio,
      6.9; 95% confidence interval, 1.02-46; P=.047) in the preceding 6 months and a
      high median calcineurin inhibitor level in the preceding 30 days (odds ratio,
      5.8; 95% confidence interval, 1.5-22; P=.012) were found to be independent risk
      factors for Nocardia infection. The majority of case patients (27 [77%] of 35)
      had pulmonary disease only. Seven transplant recipients (20%) had disseminated
      disease. Nocardia nova was the most common species (found in 17 [49%] of the
      patients), followed by Nocardia farcinica (9 [28%]), Nocardia asteroides (8
      [23%]), and Nocardia brasiliensis (1 [3%]). Of the 35 case patients, 24 (69%)
      were receiving trimethoprim-sulfamethoxazole for Pneumocystis jirovecii pneumonia
      prophylaxis. Thirty-one case patients (89%) experienced cure of their Nocardia
      infection. CONCLUSIONS: Receipt of high-dose steroids, history of cytomegalovirus
      disease, and high levels of calcineurin inhibitors are independent risk factors
      for Nocardia infection in organ transplant recipients. Our study provides
      insights into the epidemiology of Nocardia infection in the current era, a period
      in which immunosuppressive and prophylactic regimens have greatly evolved.

PMID- 17443468
TI  - Relationship between Toll-like receptor 2 polymorphism and cytomegalovirus
      disease after liver transplantation.
AB  - BACKGROUND: Experimental data suggest that cytomegalovirus (CMV) initiates innate
      immunity through the activation of Toll-like receptor 2 (TLR2). To assess the
      clinical relevance of this experimental observation, we assessed the association
      between the specific single-nucleotide polymorphism that results in the
      substitution of arginine for glutamine in position 753 of TLR2 (the TLR2
      Arg753Gln polymorphism) and CMV replication and disease after liver
      transplantation. METHODS: Ninety-two liver transplant recipients with chronic
      hepatitis C were screened for the presence of the TLR2 Arg753Gln polymorphism.
      CMV load was determined in serially collected blood samples using CMV DNA
      polymerase chain reaction. Kaplan-Meier estimation and univariable and
      multivariable stepwise Cox proportional hazard models were used to assess
      associations. RESULTS: The degree of CMV replication, as measured by CMV load,
      was significantly higher in patients who were homozygous (mean maximum viral
      load, 37,059 copies/mL) and heterozygous (mean maximum viral load, 29,718
      copies/mL) for this polymorphism, compared with patients without the TLR2
      Arg753Gln polymorphism (mean maximum viral load, 3252 copies/mL; P=.003). Kaplan
      Meier survival analysis demonstrated an association between being homozygous for
      the TLR2 Arg753Gln polymorphism and CMV disease (P=.04). A multivariate Cox
      proportional hazard model demonstrated a trend towards a higher risk of CMV
      disease among patients who were homozygous for the TLR2 Arg753Gln polymorphism
      (hazard ratio, 1.91 [95% confidence interval, 0.91-3.40]; P=.08) after adjusting
      for patient age, CMV serostatus, and allograft rejection. CONCLUSIONS: TLR2
      Arg753Gln polymorphism is possibly associated with CMV replication and disease
      after liver transplantation. This novel clinical observation supports the
      potential role of TLR2 in the immunologic control of CMV infection in humans.

PMID- 17443469
TI  - Association between high levels of blood macrophage migration inhibitory factor,
      inappropriate adrenal response, and early death in patients with severe sepsis.
AB  - BACKGROUND: Identification of new therapeutic targets remains an imperative goal
      to improve the morbidity and mortality associated with severe sepsis and septic
      shock. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine
      and counterregulator of glucocorticoids, has recently emerged as a critical
      mediator of innate immunity and experimental sepsis, and it is an attractive new
      target for the treatment of sepsis. METHODS: Circulating concentrations of MIF
      were measured in 2 clinical trial cohorts of 145 pediatric and adult patients who
      had severe sepsis or septic shock caused predominantly by infection with
      Neisseria meningitidis or other gram-negative bacteria, to study the kinetics of
      MIF during sepsis, to analyze the interplay between MIF and other mediators of
      sepsis or stress hormones (adrenocorticotropic hormone and cortisol), and to
      determine whether MIF is associated with patient outcome. RESULTS: Circulating
      concentrations of MIF were markedly elevated in 96% of children and adults who
      had severe sepsis or septic shock, and they remained elevated for several days.
      MIF levels were correlated with sepsis severity scores, presence of shock,
      disseminated intravascular coagulation, urine output, blood pH, and lactate and
      cytokine levels. High levels of MIF were associated with a rapidly fatal outcome.
      Moreover, in meningococcal sepsis, concentrations of MIF were positively
      correlated with adrenocorticotropic hormone levels and negatively correlated with
      cortisol levels and the cortisol:adrenocorticotropic hormone ratio, suggesting an
      inappropriate adrenal response to sepsis. CONCLUSIONS: MIF is markedly and
      persistently up-regulated in children and adults with gram-negative sepsis and is
      associated with parameters of disease severity, with dysregulated pituitary
      adrenal function in meningococcal sepsis, and with early death.

PMID- 17443470
TI  - Optimization of the cutoff value for the Aspergillus double-sandwich enzyme
      immunoassay.
AB  - BACKGROUND: Many health care centers worldwide use the Platelia Aspergillus
      enzyme immunoassay (PA-EIA; Bio-Rad Laboratories) for diagnosis of invasive
      aspergillosis (IA). A cutoff optical density (OD) index of 1.5 was originally
      recommended by the manufacturer, but in practice, most institutions use lower
      cutoff values. Moreover, a cutoff OD index of 0.5 was recently approved in the
      United States. In the present study, we set out to optimize the cutoff level by
      performing a retrospective analysis of PA-EIA values for samples that had been
      obtained prospectively from adult patients at risk for IA at 2 European health
      care centers. METHODS: In total, 239 treatment episodes were included of which
      there were 19 episodes of proven IA and 19 episodes of probable IA. Per-episode
      and per-test analyses and receiver operating characteristic curves were used to
      determine the optimal cutoff value. RESULTS: In the per-episode analysis,
      lowering the cutoff OD index for positivity from 1.5 to 0.5 increased the overall
      sensitivity by 21% (from 76.3% to 97.4%) but decreased the overall specificity by
      7% (from 97.5% to 90.5%). Requiring 2 consecutive samples with an OD index > or =
      0.5 resulted in the highest test accuracy, with an improved positive predictive
      value. At a cutoff OD index of 0.5, the antigen test result was positive during
      the week before conventional diagnosis in 65% of cases and during the week of
      diagnosis in 79.5% of cases. CONCLUSIONS: A cutoff OD index of 0.5--identical to
      the approved cutoff in the United States--improves the overall performance of the
      PA-EIA for adult hematology patients.

PMID- 17443471
TI  - From acute Q fever to endocarditis: serological follow-up strategy.
AB  - The serological evolution from acute Q fever to endocarditis is reported for 22
      patients, with a median lag time of 3 months. From this data, we propose a follow
      up strategy of serological testing at the third and sixth months after acute Q
      fever to obtain an early diagnosis of chronic infection.

PMID- 17443472
TI  - A child with headache, cough, weight loss, and seizure.

PMID- 17443473
TI  - Tracking the microbes in sepsis: advancements in treatment bring challenges for
      microbial epidemiology.
AB  - During the 1980s and 1990s, sepsis research propelled dozens of potential
      therapeutic candidates into clinical trials without a single novel therapeutic
      approach entering the clinical arena. After the publication of the landmark
      PROWESS trial in 2001, which showed survival benefit associated with the use of
      recombinant activated protein C for treatment of severe sepsis, there have been a
      series of positive sepsis intervention trials studying intensive glycemic
      control, low-dose steroid therapy, and early goal-directed therapy. The fact that
      the efficacy of these interventions is not restricted to certain types of
      infection should not detract from the importance of a full understanding of the
      microbial epidemiology of sepsis. Empirical antimicrobial therapy remains the
      mainstay of sepsis treatment. Furthermore, among a number of promising novel
      therapies that are in phase II and III clinical trials, several have pathogen
      specific modes of action. The optimal targeting of antibiotics and such novel
      treatments toward the specific patient groups who will benefit represents a major
      challenge to reducing sepsis mortality. This requires detailed, up-to-date, and
      local epidemiological data. It is becoming increasingly clear that the nature of
      the infection underlying sepsis is a major determinant of outcome, and future
      trials of sepsis interventions, guided by high-quality data on microbial
      epidemiology, may well have to focus on subgroups of patients with different
      forms of infection. Finally, with the rapidly increasing challenge of
      antimicrobial resistance and the paucity of novel antibiotics, particularly for
      infections with gram-negative pathogens, it is more important than ever that we
      properly understand the forces that drive changes in the microbial epidemiology
      of sepsis.

PMID- 17443475
TI  - Variability of airborne transmission of Mycobacterium tuberculosis: implications
      for control of tuberculosis in the HIV era.

PMID- 17443474
TI  - The detection of airborne transmission of tuberculosis from HIV-infected
      patients, using an in vivo air sampling model.
AB  - BACKGROUND: Nosocomial transmission of tuberculosis remains an important public
      health problem. We created an in vivo air sampling model to study airborne
      transmission of tuberculosis from patients coinfected with human immunodeficiency
      virus (HIV) and to evaluate environmental control measures. METHODS: An animal
      facility was built above a mechanically ventilated HIV-tuberculosis ward in Lima,
      Peru. A mean of 92 guinea pigs were continuously exposed to all ward exhaust air
      for 16 months. Animals had tuberculin skin tests performed at monthly intervals,
      and those with positive reactions were removed for autopsy and culture for
      tuberculosis. RESULTS: Over 505 consecutive days, there were 118 ward admissions
      by 97 patients with pulmonary tuberculosis, with a median duration of
      hospitalization of 11 days. All patients were infected with HIV and constituted a
      heterogeneous group with both new and existing diagnoses of tuberculosis. There
      was a wide variation in monthly rates of guinea pigs developing positive
      tuberculin test results (0%-53%). Of 292 animals exposed to ward air, 159
      developed positive tuberculin skin test results, of which 129 had laboratory
      confirmation of tuberculosis. The HIV-positive patients with pulmonary
      tuberculosis produced a mean of 8.2 infectious quanta per hour, compared with
      1.25 for HIV-negative patients with tuberculosis in similar studies from the
      1950s. The mean monthly patient infectiousness varied greatly, from production of
      0-44 infectious quanta per hour, as did the theoretical risk for a health care
      worker to acquire tuberculosis by breathing ward air. CONCLUSIONS: HIV-positive
      patients with tuberculosis varied greatly in their infectiousness, and some were
      highly infectious. Use of environmental control strategies for nosocomial
      tuberculosis is therefore a priority, especially in areas with a high prevalence
      of both tuberculosis and HIV infection.

PMID- 17443476
TI  - The impact of daily cotrimoxazole prophylaxis and antiretroviral therapy on
      mortality and hospital admissions in HIV-infected Zambian children.
AB  - BACKGROUND: Data on the population effectiveness of cotrimoxazole prophylaxis and
      antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected
      African children are few. METHODS: A total of 534 Zambian children with HIV
      infection were randomized to receive daily cotrimoxazole prophylaxis or placebo
      in the Children with HIV Antibiotic Prophylaxis trial. Following trial closure,
      children who received the placebo initiated cotrimoxazole prophylaxis, and all
      children were observed in a closed cohort. Mortality and hospital admission rates
      were compared, over calendar time, in 9-month periods: trial recruitment (March
      2001 to April 2002, May 2002 to January 2003), trial follow-up to closure
      (February 2003 to October 2003), initial follow-up posttrial (November 2003 to
      July 2004), and early and later ART availability (August 2004 to April 2005, and
      May 2005 to May 2006, respectively). RESULTS: A total of 546 child-years of
      follow-up, 40 deaths, and 80 hospital admissions were observed between the time
      of trial closure and June 2006. A total of 117 of 283 children who were alive at
      trial closure received ART in the posttrial period (median child age at first use
      of ART, 8.8 years). Rates decreased in both groups during the trial period,
      suggesting a survivorship effect. Mortality and hospital admission rates before
      trial closure were 14 (95% confidence interval [CI], 9-21) deaths per 100 child
      years and 24 (95% CI, 15-39) hospital admissions per 100 child-years,
      respectively, for children who were receiving cotrimoxazole, and were 23 (95% CI,
      16-34) deaths per 100 child-years and 35 (95% CI, 23-53) hospital admissions per
      100 child-years, respectively, for children who were receiving the placebo. After
      trial closure, rates remained stable in the cotrimoxazole group, but decreased to
      15 (95% CI, 8-26) deaths per 100 child-years and 19 (95% CI, 10-41) hospital
      admissions per 100 child-years, respectively, for the group of children who
      received placebo and then initiated cotrimoxazole prophylaxis. In both groups
      combined, mortality rates decreased to 6 (95% CI, 3-11) deaths per 100 child
      years and then 2 (95% CI, 0.8-6) deaths per 100 child-years during periods of ART
      availability; hospital admission rates decreased to 17 (95% CI, 11-27) hospital
      admissions per 100 child-years and 8 (95% CI, 4-15) hospital admissions per 100
      child-years, respectively. CONCLUSION: The benefits of once-daily cotrimoxazole
      prophylaxis continued throughout the trial and after trial closure. Mortality and
      hospital admissions decreased (by approximately 6-fold and approximately 3-fold,
      respectively) following ART availability, similar to findings observed in
      resource-rich countries.

PMID- 17443477
TI  - Metabolic syndrome and subclinical atherosclerosis in patients infected with HIV.
AB  - BACKGROUND: The present study examines the association between carotid and
      coronary atherosclerosis and metabolic syndrome in human immunodeficiency virus
      (HIV)-infected adults. METHODS: We measured the common and internal carotid
      intima-media thickness (c-IMT) using B-mode ultrasonography, and we measured
      coronary artery calcium (CAC) using high-resolution, electrocardiographic,
      synchronized, computed tomography, for 314 HIV-infected men and women. Metabolic
      syndrome was defined by National Cholesterol Education Program/Adult Treatment
      Panel III criteria. We compared the c-IMT measurements and CAC scores of patients
      with metabolic syndrome with the scores of those without metabolic syndrome using
      a Wilcoxon test for continuous variables and a chi2 test for categorical
      variables. To examine the association between surrogate markers and metabolic
      syndrome, we used logistic regression analysis. RESULTS: Participants with
      metabolic syndrome were more likely to have a common c-IMT measurement >0.8 mm
      than were those without metabolic syndrome (17% vs.7%; P=.009), but both groups
      were equally likely to have an internal c-IMT measurement >1.0 mm (20% vs. 13%;
      P=.15). Any positive CAC score was more likely to occur for participants with
      metabolic syndrome (80.3% vs. 46.7%; P<.0001). In a multivariate model adjusted
      for sex, age, ethnicity, and smoking status, participants with metabolic syndrome
      were more likely than those without metabolic syndrome to have an abnormal common
      c-IMT measurement (odds ratio [OR], 2.9; P=.020) and detectable CAC scores (OR,
      4.9; P<.0001) but not a higher internal c-IMT measurement (OR, 1.6; P=.255).
      CONCLUSION: Our study demonstrates that HIV-infected individuals with metabolic
      syndrome may be at increased risk for subclinical atherosclerosis and supports
      screening for metabolic syndrome among HIV-infected patients at risk for
      cardiovascular disease.

PMID- 17443481
TI  - Lamivudine and second-line antiretroviral regimens.

PMID- 17443478
TI  - Hematologic toxicity associated with interferon-based hepatitis C therapy in HIV
      type 1-coinfected subjects.
AB  - BACKGROUND: This study investigates whether dose modifications for adverse
      hematologic effects or the use of hematopoietic growth factors influenced the
      outcome of therapy for hepatitis C virus (HCV) infection in patients who were
      coinfected with HCV and human immunodeficiency virus (HIV) and who were
      participants in a randomized, controlled trial. METHODS: Subjects were randomized
      to receive ribavirin plus interferon-alfa-2a (IFN-alfa-2a) or pegylated IFN-alfa
      2a for a total of 48 weeks. Doses were modified for a number of adverse effects
      (including hematologic toxicity), and hematopoietic growth factors were
      administered at the discretion of the physician. Associations of dose
      modifications or initiation of hematopoietic growth factor support with treatment
      outcomes were determined by standard statistical methods. RESULTS: One hundred
      thirty-three subjects were included in this study. Subjects treated with
      pegylated IFN-alfa-2a were more likely to have had dose modifications (dose
      reduction or discontinuation) than were those treated with IFN-alfa-2a. By
      multivariate analysis, treatment with pegylated IFN-alfa-2a is associated with
      higher sustained virologic and/or histologic response. Dose modifications for
      nonhematologic toxicity are independently associated with lower sustained
      virologic and/or histologic responses. Although hematologic toxicity was not
      directly associated with clinical outcome in this analysis, use of hematopoietic
      growth factors was associated with an increased sustained virologic and/or
      histologic response. CONCLUSIONS: Dose modifications for anti-HCV therapy may
      adversely affect the outcome of treatment of HCV in individuals who are
      coinfected with HIV. The use of hematopoietic growth factor support may be
      associated with an improved clinical response to therapy.

PMID- 17443482
TI  - QT interval prolongation and antiretroviral treatment: another point of interest.

PMID- 17443484
TI  - Extended-spectrum beta-lactamases, food, and cephalosporin use in food animals.

PMID- 17443485
TI  - The potential impact of survivor treatment selection bias on the perceived
      efficacy of valve surgery in the treatment of infective endocarditis.

PMID- 17443486
TI  - Reducing tuberculosis incidence in HIV-infected patients by tuberculin skin
      testing, preventive treatment, and antiretroviral therapy.

PMID- 17443488
TI  - Ion chromatography/inductively coupled plasma mass spectrometry for simultaneous
      determination of glyphosate, glufosinate, fosamine and ethephon at nanogram
      levels in water.
AB  - This paper describes the first approach that simultaneously quantifies four
      polar, water-soluble organophosphorus herbicides, i.e., glyphosate, glufosinate,
      fosamine and ethephon, at nanogram levels in environmental waters. The target
      herbicides were separated completely by ion chromatography (IC) on a polymer
      anion-exchange column, Dionex IonPac AS16 (4.0 mm x 250 mm), with 30 mM citric
      acid flowing at 0.70 mL min(-1) as the eluent. On-line inductively coupled plasma
      mass spectrometry (ICP-MS) using a quadrupole mass spectrometer was employed as a
      sensitive and selective detector of the effluents. Various parameters affecting
      the separation and detection were systematically examined and optimized.
      Detection limits of the herbicides achieved with the proposed IC/ICP-MS method
      were 1.1-1.4 microg L(-1) (as compound) based on a 500-microL sample injection.
      Matrix anions, metal ions, phosphate, polyphosphates, non-polar and other polar
      organophosphorus pesticides showed no interference. The developed method was
      validated using reservoir water, treated water and NEWater samples spiked at the
      level of 10-25 microg L(-1) with satisfactory recoveries (95-109%). It is
      applicable to the simultaneous determination of microg L(-1) concentrations of
      the herbicides in polluted water.

PMID- 17443489
TI  - Studies on the metabolism of 4-methylpiperazine-1-carbodithioc acid 3-cyano-3,3-
      diphenylpropyl ester hydrochloride in rat bile by high-performance liquid
      chromatography/electrospray ionization tandem mass spectrometry.
AB  - 4-Methylpiperazine-1-carbodithioc acid 3-cyano-3,3-diphenylpropyl ester
      hydrochloride (TM208) is a newly synthesized compound which has shown excellent
      in vivo and in vitro anticancer activity and low toxicity. In the present study,
      the major metabolites of TM208 in rat bile were studied by high-performance
      liquid chromatography/tandem mass spectrometry with an electrospray ionization
      (ESI) interface. It was demonstrated that TM208 was extensively metabolized in
      rat bile and nine metabolites (M1-M9) were definitely or tentatively identified:
      (2-aminoethyl)dithiocarbamic acid 3-cyano-3,3-diphenylpropyl ester (M1), (2
      methylaminoethyl)dithiocarbamic acid 3-cyano-3,3-diphenylpropyl ester (M2), 4-[(4
      methylpiperazin-1-yl)thioxomethanesulfinyl]-2,2-diphenylbutyronitrile (M3), 4
      methylpiperazine-1-carbodithioic acid 3-cyano-3-(4-hydroxyphenyl)-3-phenylpropyl
      ester(M4), the sulfine of (4-methylpiperazine-1-carbodithioc acid 3-cyano-3,3
      diphenylpropyl ester) (M5), 4-methylpiperazine-1-carbothioic acid S-(3-cyano-3,3
      diphenylpropyl) ester (M6), piperazine-1-carbodithioic acid 3-cyano-3,3
      diphenylpropyl ester (M7), 4-hydroxymethylpiperazine-1-carbothioic acid S-(3
      cyano-3,3-diphenylpropyl) ester (M8) and the sulfine of [4-methylpiperazine-1
      carbodithioic acid 3-cyano-3-(4-hydroxyphenyl)-3-phenylpropyl ester] (M9).

PMID- 17443490
TI  - Structural characterisation of unsaturated bacterial hopanoids by atmospheric
      pressure chemical ionisation liquid chromatography/ion trap mass spectrometry.
AB  - The production of bacteriohopanepolyols (BHPs) is widespread in many different
      groups of prokaryotes; however, unsaturated components are less common except
      amongst the acetic acid bacteria. Here we describe the characterisation of mono-
      (Delta(6) or Delta(11)) and diunsaturated (Delta(6,11)) bacteriohopanetetrols
      isolated from the acetic acid bacterium Gluconacetobacter xylinus (formerly
      Acetobacter aceti ssp. xylinum) by atmospheric pressure chemical ionisation ion
      trap mass spectrometry (APCI-MS(n)). APCI-MS(2) spectra are compared with
      equivalent electron ionisation (EI) spectra and differences in fragmentation
      pathways are discussed. Having established characteristic spectral features for a
      range of unsaturated BHPs we now have the ability to rapidly detect the presence
      of unsaturated BHPs in both natural environmental samples (soils, sediments,
      water columns) as well as in microbial cultures.

PMID- 17443491
TI  - Escitalopram in a working population: results from an observational study of 2378
      outpatients in Austria.
AB  - OBJECTIVE: The aim of this observational study was to evaluate the effectiveness
      of escitalopram in a naturalistic sample of employed people with mood and anxiety
      disorders. METHOD: Days on sick leave 3 months prior and 3 months during
      treatment with escitalopram were recorded and compared (mirror study design) in
      2378 patients (949 men and 1376 women). A further clinical examination including
      the clinical global impression of severity (CGI-S) and improvement (CGI-I) scales
      and assessments of tolerability were used to evaluate treatment effects in a
      subgroup of 807 study subjects. RESULTS: Escitalopram treatment (mean final daily
      dosage: 12.4+/-5.0 mg) led to a significant reduction (baseline versus end of
      study) of sick leave (11.0+/-12.8 days versus 5.4+/-11.0 days; p<0.001). CGI-S
      scores decreased from 4.7+/-0.9 at baseline to 2.4+/-1.1 after 3 months
      (p<0.001), the CGI-I after 3 months was 1.9+/-0.9. The incidence of adverse
      events after initiation of treatment with escitalopram was 13.1%, with only 1.3%
      of patients experiencing severe adverse events interfering with patient
      functioning. CONCLUSION: Our results suggest that escitalopram is an efficacious
      and overall well-tolerated treatment in a naturalistic sample of working
      patients. A decrease in the days on sick leave is indicative of indirect cost
      effectiveness of this treatment.

PMID- 17443492
TI  - SFRP1 suppressed hepatoma cells growth through Wnt canonical signaling pathway.
AB  - Oncogenic activation of the Wnt/beta-catenin signaling pathway is common in
      hepatocellular carcinoma (HCC). The secreted frizzled-related proteins (SFRPs)
      function as negative regulators of Wnt signaling and have important implications
      for carcinogenesis. Promoter hypermethylation of SFRP genes is common in human
      cancers. However, the role of SFRPs in HCC is not clear. Recently, we have shown
      that SFRP1 is frequently downregulated through promoter hypermethylation. To
      confirm and extend these findings, the methylation status of the other SFRP
      members, including SFRP2, SFRP4 and SFRP5, was examined by methylation-specific
      polymerase chain reaction (MS-PCR). Hypermethylation of SFRP genes, except for
      SFRP4, is frequent in HCCs and the levels found here were significantly higher
      than those seen in cirrhotic livers, chronic hepatitis livers and normal controls
      (p < 0.0001 for SFRP1 and SFRP2, p < 0.05 for SFRP5). To investigate the role of
      SFRP1 in HCCs, we used re-expression of SFRP1 in beta-catenin-dependent HCC cell
      lines: Huh6 and HepG2. Restoration of SFRP1 attenuated Wnt signaling in those
      Huh6 hepatoma cells with a beta-catenin gene point mutation, decreased abnormal
      accumulation of beta-catenin in the nucleus and suppressed cell growth.
      Conversely, restoration of SFRP1 in HepG2 hepatoma cells with truncated beta
      catenin could not block the Wnt signaling pathway. Furthermore, knocking down
      SFRP1 by RNA interference in beta-catenin-deficient cell lines (SK-Hep1)
      stimulated Wnt signaling and promoted cell growth. Our data suggested that SFRP1
      suppressed liver cancer cells growth through Wnt canonical signaling. Moreover,
      beta-catenin-independent noncanonical pathway might be involved in Wnt signaling
      activation through unknown molecules in HCC.

PMID- 17443493
TI  - Evaluation of cancer virotherapy with attenuated replicative Semliki forest virus
      in different rodent tumor models.
AB  - Semliki Forest virus (SFV) is one of the latest candidates for a virotherapeutic
      agent against cancer, and recent studies have demonstrated its efficacy in tumor
      models. In the present study, we examined the antitumor efficacy of an avirulent
      SFV strain A7(74) and its derivative, a replication-competent SFV vector VA7
      EGFP, in a partially immunodeficient mouse tumor model (subcutaneous A549 human
      lung adenocarcinoma in NMRI nu/nu mouse) and in an immunocompetent rat tumor
      model (intracranial BT4C glioma in BDIX rat). When subcutaneous mouse tumors were
      injected 3 times with VA7-EGFP, intratumorally treated animals showed almost
      complete inhibition of tumor growth, while systemically treated mice displayed
      only delayed tumor growth (intravenous injection) or no response at all
      (intraperitoneal injection). This was at least partially due to a strong type I
      interferon (IFN) response in the tumors. The animals did not display any signs of
      abnormal behavior or encephalitis, even though SFV-positive foci were detected in
      the brain after the initial blood viremia. Intracranial rat tumors were injected
      directly with SFV A7(74) virus and monitored with magnetic resonance imaging.
      Tumor growth was significantly reduced (p < 0.05) with one virus injection, but
      the tumor size continued to increase after a lag period and none of the treated
      animals survived. Three virus injections or T-cell suppression with dexamethasone
      did not significantly improve treatment efficacy. It appeared that the local
      virotherapy induced extensive production of neutralizing anti-SFV antibodies that
      most likely contributed to the insufficient treatment efficacy. In conclusion, we
      show here that SFV A7(74) is a potential oncolytic agent for cancer virotherapy,
      but major immunological hurdles may need to be overcome before the virus can be
      clinically tested.

PMID- 17443495
TI  - Obesity and risk of non-Hodgkin's lymphoma: a meta-analysis.
AB  - Obesity is associated with altered immune and inflammatory responses and it may
      therefore influence the risk of non-Hodgkin's lymphoma. However, epidemiologic
      findings on obesity in relation to non-Hodgkin's lymphoma have been inconsistent.
      We conducted a meta-analysis to summarize the epidemiologic evidence on the
      association between excess body weight and risk of non-Hodgkin's lymphoma.
      Relevant studies were identified by searching MEDLINE (1966 to February 2007) and
      the reference lists of retrieved publications. We included cohort and case
      control studies that reported relative risk (RR) estimates with 95% confidence
      intervals (CIs) for the association of body mass index (BMI) with non-Hodgkin's
      lymphoma incidence or mortality. A random-effects model was used to combine
      results from individual studies. Sixteen studies (10 cohorts and 6 case-control
      studies), with 21,720 cases, met the inclusion criteria. Compared to individuals
      of normal weight (BMI < 25.0 kg/m(2)), the summary RRs of non-Hodgkin's lymphoma
      were 1.07 (95% CI, 1.01-1.14) for overweight individuals (BMI between 25 and 30
      kg/m(2)) and 1.20 (95% CI, 1.07-1.34) for those who were obese (BMI >/=>/=>/=>/=
      30.0 kg/m(2)). Meta-analysis stratified by histologic subtypes showed that
      obesity was associated with a statistically significant increased risk of diffuse
      large B-cell lymphoma (RR, 1.40; 95% CI, 1.18-1.66; n = 6 studies) but not of
      follicular lymphoma (RR, 1.10; 95% CI, 0.82-1.47; n = 6 studies) or small
      lymphocytic lymphoma/chronic lymphocytic leukemia (RR, 0.95; 95% CI, 0.76-1.20; n
      = 3 studies). These findings indicate that excess body weight is associated with
      an increased risk of non-Hodgkin's lymphoma, especially of diffuse large B-cell
      lymphoma.

PMID- 17443496
TI  - Mutations and polymorphisms of the p21B transcript in breast cancer.
AB  - p21(WAF1/CIP1), transcribed from the CDKN1A locus, plays a key role executing p53
      induced growth arrest. The recent discovery that an alternative transcript, p21B,
      induces apoptosis, suggests an additional important function of this gene. Here,
      we report p21 and p21B mutation status in large cohorts of breast cancers and
      compare distributions of p21B polymorphisms in cancer patients to healthy
      controls. In 521 breast tumor samples analyzed, only one point mutation affecting
      the p21B protein was observed. No mutations were found when screening a panel of
      20 established cell lines. A novel polymorphism, p21B(G128T) was identified.
      Haplotype analysis revealed no association between this variant and the
      previously identified p21B polymorphism p21B(T35C) or any of the known
      p21(WAF1/CIP1) polymorphisms. As previously reported for p21B(T35C), distribution
      of p21B(G128T) was similar among breast cancer patients and healthy controls (n =
      691 and 1,015; incidence 6.1 vs. 4.8%; p = 0.273, respectively). No association
      between p21B(G128T) or p21B(T35C) and response to chemotherapy with an
      anthracycline-containing regimen or paclitaxel was recorded. Our findings do not
      suggest mutations or polymorphisms of p21B to play a major role with respect to
      either breast cancer risk or sensitivity towards chemotherapy.

PMID- 17443494
TI  - Diverse roles of 2-arachidonoylglycerol in invasion of prostate carcinoma cells:
      Location, hydrolysis and 12-lipoxygenase metabolism.
AB  - Endogenous 2-arachidonoylglycerol (2-AG) is antiinvasive in androgen-independent
      prostate carcinoma (PC-3) cells. Invasion of PC-3 cells is also inhibited by
      exogenously added noladin ether, a non-hydrolyzable analog of 2-AG. In contrast,
      exogenous 2-AG has the opposite effect. Cell invasion significantly increased
      with high concentrations of exogenous 2-AG. In PC-3 cells, arachidonic acid (AA)
      and 12-hydroxyeicosatetraenoic acid (12-HETE) concentrations increased along with
      exogenously added 2-AG, and 12-HETE concentrations increased with exogenously
      added AA. Invasion of PC-3 cells also increased with exogenously added AA and
      12(S)-HETE but not 12(R)-HETE. The exogenous 2-AG-induced invasion of PC-3 cells
      was inhibited by 3-octylthio-1,1,1-trifluoropropan-2-one (OTFP, an inhibitor of 2
      AG hydrolysis) and baicalein (a 12-LO inhibitor). Western blot and RT-PCR
      analyses indicated expression of 12-HETE producing lipoxygenases (LOs), platelet
      type 12-LO (P-12-LO) and leukocyte-type 12-LO (L-12-LO), in PC-3 cells. These
      results suggest that exogenous 2-AG induced, rather inhibited, cell invasion
      because of its rapid hydrolysis to free AA, and further metabolism by 12-LO of AA
      to 12(S)-HETE, a promoter of PC cell invasion. The results also suggest that PC-3
      cells and human prostate stromal (WPMY-1) cells released free AA, 2-AG, and 12
      HETE. In the microenvironment of the PC cells, this may contribute to the cell
      invasion. The 2-AG hydrolysis and concentration of 2-AG in microenvironment are
      critical for PC cell's fate. Therefore, inhibitors of 2-AG hydrolysis could
      potentially serve as therapeutic agents for the treatment of prostate cancer. (c)
      2007 Wiley-Liss, Inc.

PMID- 17443497
TI  - DOK4/IRS-5 expression is altered in clear cell renal cell carcinoma.
AB  - The insulin-receptor substrate family plays important roles in cellular growth,
      signaling, and survival. We have previously shown the dysregulation of the IGF
      axis in clear cell renal cell carcinoma. In this manuscript, we examine the
      expression of the insulin receptor substrate family in clear cell RCC, and
      demonstrate that the expression of 2 members of this family are significantly
      altered in tumors. The most striking finding is that expression of the new IRS
      family member IRS-5 is significantly upregulated in 90% of examined clear cell
      RCCs. Studies on this gene has shown that it is regulated through chromatin
      remodeling in kidney cells.

PMID- 17443499
TI  - Zinc supplementation for improving pregnancy and infant outcome.
AB  - BACKGROUND: It has been suggested that low serum zinc levels may be associated
      with suboptimal outcomes of pregnancy such as prolonged labour, atonic postpartum
      haemorrhage, pregnancy-induced hypertension, preterm labour and post-term
      pregnancies, although many of these associations have not yet been established.
      OBJECTIVES: To assess the effects of zinc supplementation in pregnancy on
      maternal, fetal, neonatal and infant outcomes. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (February 2007).
      SELECTION CRITERIA: Randomised or quasi-randomised trials of zinc supplementation
      in pregnancy. DATA COLLECTION AND ANALYSIS: Two review authors applied the study
      selection criteria, assessed trial quality and extracted data. When necessary,
      study authors were contacted for additional information. MAIN RESULTS: We
      included 17 randomised controlled trials (RCTs) involving over 9000 women and
      their babies. Zinc supplementation resulted in a small but significant reduction
      in preterm birth (relative risk (RR) 0.86, 95% confidence interval (CI) 0.76 to
      0.98 in 13 RCTs; 6854 women). This was not accompanied by a similar reduction in
      numbers of babies with low birthweight (RR 1.05 95% CI 0.94 to 1.17; 11 studies
      of 4941 women). No significant differences were seen between the zinc and no zinc
      groups for any of the other primary maternal or neonatal outcomes, except for a
      small effect favouring zinc for caesarean section (four trials with high
      heterogeneity) and for induction of labour in a single trial. No differing
      patterns were evident in the subgroups of women with low versus normal zinc and
      nutrition levels or in women who complied with their treatment versus those who
      did not. AUTHORS' CONCLUSIONS: The 14% relative reduction in preterm birth for
      zinc compared with placebo was primarily in the group of studies involving women
      of low income and this has some relevance in areas of high perinatal mortality.
      There was no convincing evidence that zinc supplementation during pregnancy
      results in other useful and important benefits. Since the preterm association
      could well reflect poor nutrition, studies to address ways of improving the
      overall nutritional status of populations in impoverished areas, rather than
      focusing on micronutrient and or zinc supplementation in isolation, should be an
      urgent priority.

PMID- 17443500
TI  - Chlorpromazine versus placebo for schizophrenia.
AB  - BACKGROUND: Chlorpromazine, formulated in the 1950s, remains a benchmark
      treatment for people with schizophrenia. OBJECTIVES: To evaluate the effects of
      chlorpromazine for schizophrenia in comparison with placebo. SEARCH STRATEGY: We
      updated previous searches of the Cochrane Schizophrenia Group Register (October
      1999), Biological Abstracts (1982-1995), the Cochrane Library (1999, Issue 2),
      EMBASE (1980-1995), MEDLINE (1966-1995), PsycLIT (1974-1995), and the Cochrane
      Schizophrenia Group Register (June 2002), by searching The Cochrane Schizophrenia
      Group Trials Register (January 2007). We searched references of all identified
      studies for further trial citations. We contacted pharmaceutical companies and
      authors of trials for additional information. SELECTION CRITERIA: We included all
      randomised controlled trials (RCTs) comparing chlorpromazine with placebo for
      people with schizophrenia and non-affective serious/chronic mental illness
      irrespective of mode of diagnosis. Primary outcomes of interest were death,
      violent behaviours, overall improvement, relapse and satisfaction with care. DATA
      COLLECTION AND ANALYSIS: We independently inspected citations and abstracts,
      ordered papers, re-inspected and quality assessed these. BT and JR extracted
      data. CEA and GA independently checked a 10% sample for reliability. We analysed
      dichotomous data using fixed effects relative risk (RR) and estimated the 95%
      confidence interval (CI) around this. Where possible we calculated the number
      needed to treat (NNT) or number needed to harm (NNH) statistics. We excluded
      continuous data if more than 50% of participants were lost to follow up; where
      continuous data were included, we analysed this data using fixed effects weighted
      mean difference (WMD) with a 95% confidence interval. MAIN RESULTS: We inspected
      over 1000 electronic records. The review currently includes 302 excluded studies
      and 50 included studies. We found chlorpromazine reduces relapse over the short
      (n=74, 2 RCTs, RR 0.29 CI 0.1 to 0.8) and medium term (n=809, 4 RCTs, RR 0.49 CI
      0.4 to 0.6) but data are heterogeneous. Longer term homogeneous data also
      favoured chlorpromazine (n=512, 3 RCTs, RR 0.57 CI 0.5 to 0.7, NNT 4 CI 3 to 5).
      We found chlorpromazine provided a global improvement in a person's symptoms and
      functioning (n=1121, 13 RCTs, RR 'no change/not improved' 0.80 CI 0.8 to 0.9, NNT
      6 CI 5 to 8). Fewer people allocated to chlorpromazine left trials early (n=1780,
      26 RCTs, RR 0.65 CI 0.5 to 0.8, NNT 15 CI 11 to 24) compared with placebo. There
      are many adverse effects. Chlorpromazine is clearly sedating (n=1404, 19 RCTs, RR
      2.63 CI 2.1 to 3.3, NNH 5 CI 4 to 8), it increases a person's chances of
      experiencing acute movement disorders (n=942, 5 RCTs, RR 3.5 CI 1.5 to 8.0, NNH
      32 CI 11 to 154), parkinsonism (n=1265, 12 RCTs, RR 2.01 CI 1.5 to 2.7, NNH 14 CI
      9 to 28). Akathisia did not occur more often in the chlorpromazine group than
      placebo (n=1164, 9 RCTs, RR 0.78 CI 0.5 to 1.1). Chlorpromazine clearly causes a
      lowering of blood pressure with accompanying dizziness (n=1394, 16 RCTs, RR 2.37
      CI 1.7 to 3.2, NNH 11 CI 7 to 21) and considerable weight gain (n=165, 5 RCTs, RR
      4.92 CI 2.3 to 10.4, NNH 2 CI 2 to 3). AUTHORS' CONCLUSIONS: The results of this
      review confirm much that clinicians and recipients of care already know but aim
      to provide quantification to support clinical impression. Chlorpromazine's global
      position as a 'benchmark' treatment for psychoses is not threatened by the
      findings of this review. Chlorpromazine, in common use for half a century, is a
      well established but imperfect treatment. Judicious use of this best available
      evidence should lead to improved evidence-based decision making by clinicians,
      carers and patients.

PMID- 17443501
TI  - Surgical versus conservative treatment for acute injuries of the lateral ligament
      complex of the ankle in adults.
AB  - BACKGROUND: Ankle sprains are one of the most commonly treated musculoskeletal
      injuries. The three main treatment modalities for acute lateral ankle ligament
      injuries are immobilisation with plaster cast or splint, 'functional treatment'
      comprising early mobilisation and use of an external support (e.g. ankle brace),
      and surgical repair or reconstruction. OBJECTIVES: We aimed to compare surgical
      versus conservative treatment for acute injuries of the lateral ligament complex
      of the ankle in adults. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and
      Muscle Trauma Group Specialised Register (January 2006), the Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue 4), MEDLINE (1966
      to December 2005), EMBASE, CINAHL and reference lists of articles, and contacted
      researchers in the field. This review is considered updated to January 2006.
      SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing
      surgical with conservative interventions for treating ankle sprains in adults.
      DATA COLLECTION AND ANALYSIS: At least two authors independently assessed
      methodological quality and extracted data. Where appropriate, results of
      comparable studies were pooled. We performed sensitivity analyses to explore the
      robustness of the findings. MAIN RESULTS: Twenty trials were included. These
      involved a total of 2562 mostly young active adult males. All trials had
      methodological weaknesses. Specifically, concealment of allocation was confirmed
      in only one trial. Data for pooling individual outcomes were only available for a
      maximum of 12 trials and under 60% of participants. The findings of statistically
      significant differences in favour of the surgical treatment group for the four
      primary outcomes (non-return to pre-injury level of sports; ankle sprain
      recurrence; long-term pain; subjective or functional instability) when using the
      fixed-effect model were not robust when using the random-effects model, nor on
      the removal of one low quality (quasi-randomised) trial that had more extreme
      results. A corresponding drop in the I(2) statistics showed the remaining trials
      to be more homogeneous. The functional implications of the statistically
      significantly higher incidence of objective instability in conservatively treated
      trial participants are uncertain. There was some limited evidence for longer
      recovery times, and higher incidences of ankle stiffness, impaired ankle mobility
      and complications in the surgical treatment group. AUTHORS' CONCLUSIONS: There is
      insufficient evidence available from randomised controlled trials to determine
      the relative effectiveness of surgical and conservative treatment for acute
      injuries of the lateral ligament complex of the ankle. High quality randomised
      controlled trials of primary surgical repair versus the best available
      conservative treatment for well-defined injuries are required.

PMID- 17443502
TI  - Antibiotics for asymptomatic bacteriuria in pregnancy.
AB  - BACKGROUND: Asymptomatic bacteriuria occurs in 2% to 10% of pregnancies and, if
      not treated, up to 30% of mothers will develop acute pyelonephritis. Asymptomatic
      bacteriuria has been associated with low birthweight and preterm delivery.
      OBJECTIVES: To assess the effect of antibiotic treatment for asymptomatic
      bacteriuria on persistent bacteriuria during pregnancy, the development of
      pyelonephritis and the risk of low birthweight and preterm delivery. SEARCH
      STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (January 2007). SELECTION CRITERIA: Randomized trials comparing
      antibiotic treatment with placebo or no treatment in pregnant women with
      asymptomatic bacteriuria found on antenatal screening. DATA COLLECTION AND
      ANALYSIS: We assessed trial quality. MAIN RESULTS: Fourteen studies were
      included. Overall the study quality was poor. Antibiotic treatment compared to
      placebo or no treatment was effective in clearing asymptomatic bacteriuria (risk
      ratio (RR) 0.25, 95% confidence interval (CI) 0.14 to 0.48). The incidence of
      pyelonephritis was reduced (RR 0.23, 95% CI 0.13 to 0.41). Antibiotic treatment
      was also associated with a reduction in the incidence of low birthweight babies
      (RR 0.66, 95% CI 0.49 to 0.89) but a difference in preterm delivery was not seen.
      AUTHORS' CONCLUSIONS: Antibiotic treatment is effective in reducing the risk of
      pyelonephritis in pregnancy. A reduction in low birthweight is consistent with
      current theories about the role of infection in adverse pregnancy outcomes, but
      this association should be interpreted with caution given the poor quality of the
      included studies.

PMID- 17443503
TI  - Interventions for preventing and treating pelvic and back pain in pregnancy.
AB  - BACKGROUND: More than two-thirds of pregnant women experience back pain and
      almost one-fifth experience pelvic pain. The pain increases with advancing
      pregnancy and interferes with work, daily activities and sleep. OBJECTIVES: To
      assess the effects of interventions for preventing and treating back and pelvic
      pain in pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Review Group's Trials Register (February 2006). SELECTION CRITERIA:
      Randomised controlled trials of any treatment to prevent or reduce the incidence
      or severity of back or pelvic pain in pregnancy. DATA COLLECTION AND ANALYSIS:
      Two authors independently assessed trial quality and extracted data. MAIN
      RESULTS: We found no studies dealing specifically with prevention of back or
      pelvic pain. We included eight studies (1305 participants) that examined the
      effects of adding various pregnancy-specific exercises, physiotherapy,
      acupuncture and pillows to usual prenatal care. For women with low-back pain,
      participating in strengthening exercises, sitting pelvic tilt exercises
      (standardised mean difference (SMD) -5.34; 95% confidence interval (CI) -6.40 to 
      4.27), and water gymnastics reduced pain intensity and back pain-related sick
      leave (relative risk (RR) 0.40; 95% CI 0.17 to 0.92) better than usual prenatal
      care alone. The specially-designed Ozzlo pillow was more effective than a regular
      one in relieving back pain (RR 1.84; 95% CI 1.32 to 2.55), but is no longer
      commercially available. Both acupuncture and stabilising exercises relieved
      pelvic pain more than usual prenatal care. Acupuncture gave more relief from
      evening pain than exercises. For women with both pelvic and back pain, in one
      study, acupuncture was more effective than physiotherapy in reducing the
      intensity of their pain; stretching exercises resulted in more total pain relief
      (60%) than usual care (11%); and 60% of those who received acupuncture reported
      less intense pain, compared to 14% of those receiving usual prenatal care. Women
      who received usual prenatal care reported more use of analgesics, physical
      modalities and sacroiliac belts. AUTHORS' CONCLUSIONS: All but one study had
      moderate to high potential for bias, so results must be viewed cautiously. Adding
      pregnancy-specific exercises, physiotherapy or acupuncture to usual prenatal care
      appears to relieve back or pelvic pain more than usual prenatal care alone,
      although the effects are small. We do not know if they actually prevent pain from
      starting in the first place. Water gymnastics appear to help women stay at work.
      Acupuncture shows better results compared to physiotherapy.

PMID- 17443504
TI  - Vaccines for preventing influenza in healthy adults.
AB  - BACKGROUND: Different types of influenza vaccines are currently produced world
      wide. Healthy adults are at present targeted only in North America. Despite the
      publication of a large number of clinical trials, there is still substantial
      uncertainty about the clinical effectiveness of influenza vaccines and this has a
      negative impact on their acceptance and uptake. OBJECTIVES: To identify, retrieve
      and assess all studies evaluating the effects (efficacy, effectiveness and harms)
      of vaccines against influenza in healthy adults. SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library,
      Issue 4, 2005) which contains the Cochrane Acute Respiratory Infections Group
      trials register; MEDLINE (January 1966 to January 2006); and EMBASE (1990 to
      January 2006). We wrote to vaccine manufacturers and first or corresponding
      authors of studies in the review. SELECTION CRITERIA: Any randomised or quasi
      randomised studies comparing influenza vaccines in humans with placebo, no
      intervention. Live, attenuated, or killed vaccines or fractions of them
      administered by any route, irrespective of antigenic configuration were assessed.
      Only studies assessing protection from exposure to naturally occurring influenza
      in healthy individuals aged 16 to 65 years were considered. Comparative non
      randomised studies were included if they assessed evidence of the possible
      association between influenza vaccines and serious harms. DATA COLLECTION AND
      ANALYSIS: Two review authors independently assessed trial quality and extracted
      data. MAIN RESULTS: Forty-eight reports were included: 38 (57 sub-studies) were
      clinical trials providing data about effectiveness, efficacy and harms of
      influenza vaccines and involved 66,248 people; 8 were comparative non-randomised
      studies and tested the association of the vaccines with serious harms; 2 were
      reports of harms which could not be introduced in the data analysis. Inactivated
      parenteral vaccines were 30% effective (95% CI 17% to 41%) against influenza-like
      illness, and 80% (95% CI 56% to 91%) efficacious against influenza when the
      vaccine matched the circulating strain and circulation was high, but decreased to
      50% (95% CI 27% to 65%) when it did not. Excluding the studies of the 1968 to
      1969 pandemic, effectiveness was 15% (95% CI 9% to 22%) and efficacy was 73% (95%
      CI 53% to 84%). Vaccination had a modest effect on time off work, but there was
      insufficient evidence to draw conclusions on hospital admissions or complication
      rates. Inactivated vaccines caused local tenderness and soreness and erythema.
      Spray vaccines had more modest performance. Monovalent whole-virion vaccines
      matching circulating viruses had high efficacy (VE 93%, 95% CI 69% to 98%) and
      effectiveness (VE 66%, 95% CI 51% to 77%) against the 1968 to 1969 pandemic.
      AUTHORS' CONCLUSIONS: Influenza vaccines are effective in reducing cases of
      influenza, especially when the content predicts accurately circulating types and
      circulation is high. However, they are less effective in reducing cases of
      influenza-like illness and have a modest impact on working days lost. There is
      insufficient evidence to assess their impact on complications. Whole-virion
      monovalent vaccines may perform best in a pandemic.

PMID- 17443505
TI  - Surgical interventions for lumbar disc prolapse.
AB  - BACKGROUND: Disc prolapse accounts for five percent of low-back disorders but is
      one of the most common reasons for surgery. OBJECTIVES: The objective of this
      review was to assess the effects of surgical interventions for the treatment of
      lumbar disc prolapse. SEARCH STRATEGY: We searched the Cochrane Central Register
      of Controlled Trials, MEDLINE, PubMed, Spine and abstracts of the main spine
      society meetings within the last five years. We also checked the reference lists
      of each retrieved articles and corresponded with experts. All data found up to 1
      January 2007 are included. SELECTION CRITERIA: Randomized trials (RCT) and quasi
      randomized trials (QRCT) of the surgical management of lumbar disc prolapse. DATA
      COLLECTION AND ANALYSIS: Two review authors assessed trial quality and extracted
      data from published papers. Additional information was sought from the authors if
      necessary. MAIN RESULTS: Forty RCTs and two QRCTs were identified, including 17
      new trials since the first edition of this review in 1999. Many of the early
      trials were of some form of chemonucleolysis, whereas the majority of the later
      studies either compared different techniques of discectomy or the use of some
      form of membrane to reduce epidural scarring. Despite the critical importance of
      knowing whether surgery is beneficial for disc prolapse, only four trials have
      directly compared discectomy with conservative management and these give
      suggestive rather than conclusive results. However, other trials show that
      discectomy produces better clinical outcomes than chemonucleolysis and that in
      turn is better than placebo. Microdiscectomy gives broadly comparable results to
      standard discectomy. Recent trials of an inter-position gel covering the dura
      (five trials) and of fat (four trials) show that they can reduce scar formation,
      though there is limited evidence about the effect on clinical outcomes. There is
      insufficient evidence on other percutaneous discectomy techniques to draw firm
      conclusions. Three small RCTs of laser discectomy do not provide conclusive
      evidence on its efficacy, There are no published RCTs of coblation therapy or
      trans-foraminal endoscopic discectomy. AUTHORS' CONCLUSIONS: Surgical discectomy
      for carefully selected patients with sciatica due to lumbar disc prolapse
      provides faster relief from the acute attack than conservative management,
      although any positive or negative effects on the lifetime natural history of the
      underlying disc disease are still unclear. Microdiscectomy gives broadly
      comparable results to open discectomy. The evidence on other minimally invasive
      techniques remains unclear (with the exception of chemonucleolysis using
      chymopapain, which is no longer widely available).

PMID- 17443506
TI  - Prolonged antibiotics for purulent bronchiectasis in children and adults.
AB  - BACKGROUND: The vicious cycle hypothesis for bronchiectasis predicts that
      bacterial colonisation of the respiratory tract perpetuates inflammatory change.
      This damages the mucociliary escalator preventing bacterial clearance and
      allowing the persistence of pro-inflammatory mediators. Conventional treatment
      with physiotherapy and intermittent antibiotics are felt to improve the condition
      of bronchiectasis patients although there are no conclusive data showing that
      these interventions influence the natural history of the condition. Various
      strategies have been tried to interrupt this cycle of infection and inflammation
      and one of these is to prolong antibiotic treatment in the hope of allowing the
      airway mucosa to heal. OBJECTIVES: This systematic review brings together the
      evidence and where possible presents a meta-analysis of the data available to
      answer the question 'Does treatment with prolonged courses of antibiotics
      influence the outcome in purulent bronchiectasis?' SEARCH STRATEGY: The Cochrane
      Airways Group trials register and reference lists of identified articles were
      searched. Searches were current as of January 2007. SELECTION CRITERIA:
      Randomised trials looking at the use of prolonged antibiotic therapy in the
      treatment of bronchiectasis compared with either placebo or usual care. DATA
      COLLECTION AND ANALYSIS: Trial quality was assessed and data extraction was
      carried out by the reviewers independently. Study authors were contacted for
      missing information. MAIN RESULTS: Nine trials met the inclusion criteria,
      recruiting a total of 378 participants. Antibiotics were given for between 4
      weeks and one year. Only limited meta-analysis was possible due to the diversity
      of outcomes in the trials. Response rates showed significant effects in favour of
      prolonged antibiotic treatment (Peto OR (95% CI), 3.37 (1.60 to 7.09)).
      Conversely for exacerbation rates there was no significant difference between
      prolonged antibiotics and placebo (Peto OR (95% CI), 0.96 (0.27 to 3.46)). For
      withdrawals there was no significant difference between treatment and placebo
      management (Peto OR (95% CI), 1.06 (0.42 to 2.65)). Data for lung function showed
      no significant benefit in favour of antibiotic treatment (% predicted FEV1 mean
      difference -1.05 % (95% CI -6.93 to 4.83)). AUTHORS' CONCLUSIONS: The evidence
      available shows a small benefit for the use of prolonged antibiotics in the
      treatment of bronchiectasis. This review is limited by the diversity of the
      trials. Further randomised controlled trials with adequate power and standardised
      end points are required.

PMID- 17443507
TI  - Absorbent products for light urinary incontinence in women.
AB  - BACKGROUND: Incontinence is a common and embarrassing problem which has a
      profound effect on social and psychological well-being. Many people wear
      absorbent products to contain urine leakage and protect their clothes. It can be
      difficult to define light urinary incontinence because urine volumes, flow and
      frequency rates may vary substantially whilst still being considered 'light'.
      Light incontinence may encompass occasional (monthly) leaks of very small amounts
      (e.g. 1 g to 2 g) up to frequent leaks (several times per day) of larger amounts
      (e.g. 20 g to 50 g). A practical definition is urine loss that can be contained
      within a small absorbent pad (typically 50 g to 500 g; ISO 1996). OBJECTIVES: To
      assess the effectiveness of different types of absorbent product designs for
      women with light urinary incontinence. SEARCH STRATEGY: We searched the Cochrane
      Incontinence Group Specialised Trials Register (3 May 2006) and the reference
      lists of relevant articles were perused. SELECTION CRITERIA: TYPES OF STUDIES:
      All randomised or quasi-randomised trials of absorbent products for women with
      light urinary incontinence. TYPES OF PARTICIPANTS: Women with light urinary
      incontinence. TYPES OF INTERVENTION: Absorbent products (disposable insert pads,
      menstrual pads, washable pants with integral pad, washable insert pads) suitable
      for light incontinence. DATA COLLECTION AND ANALYSIS: Two review authors assessed
      the methodological quality of potentially eligible studies and independently
      extracted data from the included trial. MAIN RESULTS: One study with 85
      participants met the selection criteria. This trial studied all the absorbent
      product designs included in this review. Data were presented on all included
      outcomes. For preventing leakage, for preference and for overall acceptability
      disposable insert pads are better than disposable menstrual pads which are better
      than washable pants with integral pad which are better than washable insert pads.
      There is no strong evidence that either disposables or washables are better for
      skin health. The disposable insert is the most expensive design and there is no
      dominant design for cost-effectiveness. There is evidence that some women will
      prefer alternative designs which are all cheaper than disposable inserts.
      AUTHORS' CONCLUSIONS: Although data were available from only one eligible trial
      the data were sufficiently robust to make recommendations for practice.
      Disposable insert pads are typically more effective than the other designs
      considered. However, because they are the most expensive, providing choice of
      designs (or combinations of designs for different circumstances) is likely to be
      cost-effective.

PMID- 17443508
TI  - Local corticosteroid injection for carpal tunnel syndrome.
AB  - BACKGROUND: Carpal tunnel syndrome is a clinical syndrome manifested by signs and
      symptoms of irritation of the median nerve at the carpal tunnel in the wrist.
      Local corticosteroid injection for carpal tunnel syndrome has been studied but
      its effectiveness is unknown. OBJECTIVES: To evaluate the effectiveness of local
      corticosteroid injection for carpal tunnel syndrome versus placebo injection or
      other non-surgical interventions. SEARCH STRATEGY: We searched the Cochrane
      Neuromuscular Disease Group Trials register (searched May 2006), MEDLINE
      (searched January 1966 to May 2006), EMBASE (searched January 1980 to May 2006)
      and CINAHL (searched January 1982 to May 2006). SELECTION CRITERIA: Randomized or
      quasi-randomized studies. DATA COLLECTION AND ANALYSIS: Three authors
      independently selected the trials and rated their overall quality. Relative risks
      and 95% confidence intervals were calculated for each trial and summary relative
      risks and 95% confidence intervals were also calculated. MAIN RESULTS: We
      included 12 studies with altogether 671 participants. Two high quality randomized
      controlled trials with altogether 141 participants demonstrated clinical
      improvement of carpal tunnel syndrome at one month or less following local
      corticosteroid compared to placebo injection (relative risk 2.58 (95% confidence
      intervals 1.72 to 3.87)). One trial compared local corticosteroid injection to
      oral corticosteroid and at 12 weeks after treatment there was significantly more
      improvement in the injection group (mean difference -7.10 (95% confidence
      intervals -11.68 to -2.52)). In one trial, the rate of improvement after one
      month was greater after local than systemic corticosteroid injection (relative
      risk 3.17 (95% confidence intervals 1.02 to 9.87)). In one trial, symptoms did
      not improve significantly more in the injection group at eight weeks after
      injection compared to treatment with anti-inflammatory medication and splinting
      (mean difference 0.10 (95% confidence intervals -0.33 to 0.53)). Two injections
      versus one injection of local corticosteroid did not provide further clinical
      improvement, mean difference -3.80 (95% CI -9.27 to 1.67). AUTHORS' CONCLUSIONS:
      Local corticosteroid injection for carpal tunnel syndrome provides greater
      clinical improvement in symptoms one month after injection compared to placebo.
      Significant symptom relief beyond one month has not been demonstrated. Local
      corticosteroid injection provides significantly greater clinical improvement than
      oral corticosteroid for up to three months. Local corticosteroid injection does
      not significantly improve clinical outcome compared to either anti-inflammatory
      treatment and splinting after eight weeks or Helium-Neon laser treatment after
      six months. Two local corticosteroid injections do not provide significant added
      clinical benefit compared to one injection.

PMID- 17443509
TI  - Conjugate vaccines for preventing Haemophilus influenzae type B infections.
AB  - BACKGROUND: Haemophilus influenzae (H. influenzae) is an important cause of
      meningitis and pneumonia in children. Vaccine cost is a significant barrier to
      use in low income countries. Determining the size of the effects of the vaccine
      will enable cost-effectiveness comparisons with competing priorities in low
      income countries. OBJECTIVES: 1. To determine the effects of conjugate Hib
      vaccine in preventing Hib disease or death in children under five years of age.2.
      To determine any variation in effect with type of vaccine, number of doses, age
      at first dose, in children with known HIV infection, or in high and low income
      countries.3. To determine any serious adverse outcomes. SEARCH STRATEGY: We
      searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library, Issue 4, 2006); MEDLINE (January 1966 to December 2006); EMBASE
      (1990 to June 2006) and scanned reference lists and contacting of authors of
      trial reports. Reports in all languages were considered. SELECTION CRITERIA: All
      randomised controlled trials (RCTs) or quasi-RCTs of conjugate H. influenzae type
      b vaccines compared with placebo or no treatment in children who were followed
      until at least two years of age. DATA COLLECTION AND ANALYSIS: Two review authors
      independently selected eligible studies and extracted data. MAIN RESULTS: Six
      studies were included in the review, and four in the meta-analyses. The overall
      quality of the trials was good. The relative risk for invasive Hib disease was
      0.20 (95% confidence interval (CI) 0.07 to 0.54; random-effects model), but there
      was statistically significant unexplained variation (heterogeneity) in the
      effects of the four trials in the meta-analysis (P = 0.002). The size of the
      effects did not appear to differ consistently with different vaccine types, the
      number of vaccine doses, age at first vaccination or use in high income versus
      low income countries, but the CIs for the effect estimates were wide. Hib-related
      mortality data showed a non-significant trend towards benefit (relative risk was
      0.29; 95% CI 0.07 to 1.20; random-effects model). The relative risk for all cause
      mortality in the two trials from which data were available were 1.01 (95% CI 0.38
      to 2.67, random-effects model) and 0.97. No serious adverse effects were reported
      in any of the trials. AUTHORS' CONCLUSIONS: Hib vaccine is safe and effective. In
      resource-poor settings, decisions to use the vaccine will depend on its cost, the
      local burden of Hib disease and competing priorities.

PMID- 17443510
TI  - Skin grafting for venous leg ulcers.
AB  - BACKGROUND: Venous leg ulceration is a recurrent, chronic, disabling condition.
      It affects up to one in 100 adults at some time. Standard treatments are simple
      dressings and compression bandages or stockings. Sometimes, despite treatment,
      ulcers remain open for months or years. Sometimes skin grafts are used to
      stimulate healing. These may be taken, or grown into a dressing, from the
      patient's own uninjured skin (autografts), or applied as a sheet of bioengineered
      skin grown from donor cells (allograft). Preserved skin from other animals, such
      as pigs, has also been used (xenografts). OBJECTIVES: To assess the effect of
      skin grafts for treating venous leg ulcers. SEARCH STRATEGY: We searched the
      Cochrane Wounds Group Specialised Register (February 2006) and the Cochrane
      Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2006).
      SELECTION CRITERIA: Randomised controlled trials (RCTs) of skin grafts in the
      treatment of venous leg ulcers. DATA COLLECTION AND ANALYSIS: Two reviewers
      independently undertook data extraction and assessment of study quality. MAIN
      RESULTS: We identified 15 trials - generally of poor methodological quality -
      involving 768 participants. In 11 trials participants also received compression
      bandaging. One trial (31 participants) compared a dressing with an autograft.
      Three trials (74 participants) compared frozen allografts with dressings, and
      three trials (47 participants) compared fresh allografts with dressings. Two
      trials (345 participants) compared tissue-engineered skin (bilayer artificial
      skin) with a dressing. In two trials (71 participants) a single-layer dermal
      replacement was compared with standard care. Four trials compared skin grafting
      techniques: one trial (92 participants) compared autografts with frozen
      allograft, a second (51 participants) compared a pinch graft (autograft) with a
      porcine dermis (xenograft), the third (seven participants, 12 ulcers) compared
      tissue-engineered skin with a split-thickness graft, the fourth (10 participants)
      compared a fresh allograft with a frozen allograft. The trials comparing bilayer
      artificial skin with a dressing reported a significantly higher proportion of
      ulcers healing with artificial skin. There was not enough evidence from the other
      trials to determine whether other types of skin grafting increased the healing of
      venous ulcers. AUTHORS' CONCLUSIONS: Bilayer artificial skin, used in conjunction
      with compression bandaging, increases the chance of healing a venous ulcer
      compared with compression and a simple dressing. Further research is needed to
      assess whether other forms of skin grafts increase ulcer healing.

PMID- 17443511
TI  - Surgery for faecal incontinence in adults.
AB  - BACKGROUND: Faecal incontinence is a debilitating problem with significant
      medical, social and economic implications. Treatment options include
      conservative, non-surgical interventions (e.g. pelvic floor muscle training,
      biofeedback, drugs, sacral nerve stimulation) and surgical procedures. A surgical
      procedure may be aimed at correcting an obvious mechanical defect, or augmenting
      a functionally deficient but structurally intact sphincter complex or replace an
      absent/non-functioning sphincter. OBJECTIVES: To assess the effects of surgical
      techniques for the treatment of faecal incontinence in adults who do not have
      rectal prolapse. Our aim was firstly to compare surgical management with non
      surgical management and secondly, to compare the various surgical techniques.
      SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials
      Register (31 January 2006), the Cochrane Colorectal Cancer Group trials register
      (31 January 2006), the Cochrane Central Register of Controlled Trials (2006,
      Issue 1), PubMed (1 January 1950 to 31 January 2006) and EMBASE (1 January 1998
      to 31 January 2006) were undertaken. The British Journal of Surgery (January 1995
      to May 2006) Colorectal Diseases (January 2000-May 2006) and the Diseases of the
      Colon and Rectum (January 1995 to May 2006) were specifically handsearched. The
      proceedings of the Association of Coloproctology meeting held from 1999 to 2006
      were perused. Reference lists of all relevant articles were searched for further
      trials. SELECTION CRITERIA: All randomised or quasi-randomised trials of surgery
      in the management of adult faecal incontinence (other than surgery for rectal
      prolapse). DATA COLLECTION AND ANALYSIS: Two reviewers independently selected
      studies from the literature searches, assessed the methodological quality of
      eligible trials and extracted data. The three primary outcome measures were:
      change or deterioration in incontinence, failure to achieve full continence, and
      the presence of faecal urgency. MAIN RESULTS: Nine trials were included with a
      total sample size of 264 participants. Two trials included a group managed non
      surgically. One trial compared levatorplasty with anal plug stimulation, one
      compared artificial bowel sphincter with best supportive care; numbers were small
      in both trials. The artificial bowel sphincter insertion was followed by
      significant improvements in at least one primary outcome but with high rates of
      significant morbidity. Seven studies compared different surgical interventions.
      These included anterior levatorplasty versus postanal repair, anterior
      levatorplasty versus total pelvic floor repair, total pelvic floor versus
      postanal repair, end to end versus overlap sphincter repair, overlap repair with
      or without a defunctioning stoma or with or without biofeedback, total pelvic
      floor repair versus repair plus internal sphincter plication and neosphincter
      formation versus total pelvic floor repair. Only one comparison had more that one
      trial (total pelvic floor versus postanal repair-44 participants) and no
      comparison showed any statistically significant difference in primary outcome
      measures, with wide confidence intervals. AUTHORS' CONCLUSIONS: Despite more
      studies being included in this update, the continued small number of relevant
      trials identified together with their small sample sizes and other methodological
      weaknesses continue to limit the usefulness of this review for guiding practice.
      It was impossible to identify or refute clinically important differences between
      the alternative surgical procedures. Larger rigorous trials are still needed.
      However, it should be recognised that the optimal treatment regime may be a
      complex combination of various surgical and non-surgical therapies.

PMID- 17443512
TI  - Conservative management for postprostatectomy urinary incontinence.
AB  - BACKGROUND: Urinary incontinence is common after both radical prostatectomy (RP)
      and transurethral resection of the prostate (TURP). Conservative management
      includes pelvic floor muscle training (PFMT) with or without biofeedback,
      electrical stimulation, compression devices (penile clamps), lifestyle changes,
      extra-corporeal magnetic innervation or a combination of methods. OBJECTIVES: To
      assess the effects of conservative management for urinary incontinence after
      prostatectomy. SEARCH STRATEGY: We searched the Cochrane Incontinence Group
      Specialised Trials Register (searched 23 January 2006), MEDLINE (January 1966 to
      January 2006), EMBASE (January 1988 to January 2006), CINAHL (January 1982 to
      January 2006), PsycLIT (January 1984 to January 2006), ERIC (January 1984 to
      January 2006), the reference lists of relevant articles, handsearched conference
      proceedings and contacted investigators to locate studies. SELECTION CRITERIA:
      Randomised or quasi-randomised controlled trials evaluating conservative
      interventions for urinary continence after prostatectomy. DATA COLLECTION AND
      ANALYSIS: At least two review authors assessed the methodological quality of
      trials and abstracted data. MAIN RESULTS: Seventeen trials met the inclusion
      criteria, fifteen trials amongst men after radical prostatectomy (RP), one trial
      after transurethral resection of the prostate (TURP) and one trial after either
      operation. There was considerable variation in the interventions, populations and
      outcome measures. The majority of trials in this area continue to be of moderate
      quality, although more recent studies have been of higher quality in terms of
      both randomization and blinding. Data were not available in all the trials for
      many of the pre-stated outcomes. Confidence intervals have tended to be wide
      except for the more recent studies, and it continues to be difficult to reliably
      identify or rule out a useful effect. There were several important variations in
      the populations being studied. Therefore the decision was made by the review
      authors to separate in the analysis the men having the intervention as prevention
      (whether administered before or after operation, to all men having surgery) or as
      treatment (postoperatively to those men who did have urinary incontinence), as
      well as separating those treated with TURP or RP. Amongst seven treatment trials
      of postoperative PFMT for urinary incontinence after RP, one trial suggested
      benefits, whereas the estimates from the others were consistent with no effect.
      There was clinical and statistical heterogeneity, precluding meta-analysis. There
      was no clear reason for this heterogeneity. Trials of preventative PFMT started
      pre or post-operatively also showed heterogeneity: only one large trial favoured
      PFMT but the data from the others were conflicting. Analysis of other
      conservative interventions such as transcutaneous electrical nerve stimulation
      and anal electrical stimulation, or combinations of these interventions were
      inconclusive. There were too few data to determine treatment effects on
      incontinence after TURP. The findings should continue to be treated with caution,
      as most studies were of poor to moderate quality. With respect to other
      management, men in one trial reported a preference for one type of external
      compression device compared to two others or no treatment. The effect of other
      conservative interventions such as lifestyle changes remains undetermined as no
      trials involving these interventions were identified. Men's symptoms tended to
      improve over time, irrespective of management. AUTHORS' CONCLUSIONS: The value of
      the various approaches to conservative management of postprostatectomy
      incontinence remains uncertain. Long-term incontinence may be managed by external
      penile clamp, but there are safety problems.

PMID- 17443513
TI  - Interventions for treating oral candidiasis for patients with cancer receiving
      treatment.
AB  - BACKGROUND: Treatment of cancer is increasingly effective but is associated with
      short and long term side effects. Oral side effects, including oral candidiasis,
      remain a major source of illness despite the use of a variety of agents to treat
      them. OBJECTIVES: To assess the effectiveness of interventions for the treatment
      of oral candidiasis for patients with cancer receiving chemotherapy or
      radiotherapy or both. SEARCH STRATEGY: Computerised searches of Cochrane Oral
      Health Group and PaPaS Trials Registers, CENTRAL, MEDLINE, EMBASE, CINAHL,
      CANCERLIT, SIGLE and LILACS were undertaken. Reference lists from relevant
      articles were searched and the authors of eligible trials were contacted to
      identify trials and obtain additional information. Date of the most recent
      searches: June 2006: CENTRAL (The Cochrane Library 2006, Issue 2). SELECTION
      CRITERIA: All randomised controlled trials comparing agents prescribed to treat
      oral candidiasis in people receiving chemotherapy or radiotherapy for cancer. The
      outcomes were eradication of oral candidiasis, dysphagia, systemic infection,
      amount of analgesia, length of hospitalisation, cost and patient quality of life.
      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. Risk ratios were calculated
      using random-effects models. MAIN RESULTS: Nine trials involving 658 patients,
      satisfied the inclusion criteria and are included in this review. Only two
      agents, each in single trials, were found to be effective for eradicating oral
      candidiasis. A drug absorbed from the gastrointestinal tract, ketoconazole, was
      more beneficial than placebo in eradicating oral candidiasis (risk ratio (RR) =
      3.61, 95% confidence interval (CI) 1.47 to 8.88) and clotrimazole, at a higher
      dose of 50 mg was more effective than a lower 10 mg dose in eradicating oral
      candidiasis, when assessed mycologically (RR = 2.00, 95% CI 1.11 to 3.60). Of the
      five trials included in these meta-analyses, three were at high risk of bias and
      two of moderate risk of bias. Another trial demonstrated no statistically
      significant difference between a 10 mg dose of the partially absorbed drug,
      clotrimazole, and placebo. No differences were found when comparing different
      absorbed drugs; and comparing absorbed drugs with drugs which are not absorbed.
      AUTHORS' CONCLUSIONS: There is weak and unreliable evidence that the absorbed
      drug, ketoconazole, may eradicate oral candidiasis and that a higher dose of the
      partially absorbed drug, clotrimazole, may give greater benefit than a lower 10
      mg dose, however, researchers may wish to prevent rather than treat oral
      candidiasis. Further well designed, placebo-controlled trials assessing the
      effectiveness of old and new interventions for treating oral candidiasis are
      needed.

PMID- 17443514
TI  - Interventions for treating oral mucositis for patients with cancer receiving
      treatment.
AB  - BACKGROUND: Treatment of cancer is increasingly effective but associated with
      short and long term side effects. Oral side effects, including oral mucositis
      (mouth ulceration), remain a major source of illness despite the use of a variety
      of agents to treat them. OBJECTIVES: To assess the effectiveness of interventions
      for treating oral mucositis or its associated pain in patients with cancer
      receiving chemotherapy or radiotherapy or both. SEARCH STRATEGY: Computerised
      searches of Cochrane Oral Health Group's Trials Register; Cochrane Pain,
      Palliative and Supportive Care Group's Trials Register; CENTRAL; MEDLINE and
      EMBASE were undertaken. Reference lists from relevant articles were searched and
      the authors of eligible trials were contacted to identify trials and obtain
      additional information. Date of the most recent searches June 2006: CENTRAL (The
      Cochrane Library 2006, Issue 2). SELECTION CRITERIA: All randomised controlled
      trials comparing agents prescribed to treat oral mucositis in people receiving
      chemotherapy or radiotherapy or both. Outcomes were oral mucositis, time to heal
      mucositis, oral pain, duration of pain control, dysphagia, systemic infection,
      amount of analgesia, length of hospitalisation, cost and quality of life. DATA
      COLLECTION AND ANALYSIS: Data were independently extracted, in duplicate, by two
      review authors. Authors were contacted for details of randomisation, blindness
      and withdrawals. Quality assessment was carried out on these three criteria. The
      Cochrane Oral Health Group statistical guidelines were followed and risk ratio
      (RR) values calculated using fixed effect models. MAIN RESULTS: Twenty-six trials
      involving 1353 patients satisfied the inclusion criteria. Four agents, each in
      single trials, were found to be effective for improving (allopurinol RR 3.33, 95%
      confidence interval (CI) 1.06 to 10.49; granulocyte macrophage-colony stimulating
      factor RR 4.23, 95% CI 1.35 to 13.24; immunoglobulin RR 1.81, 95% CI 1.24 to
      2.65; human placentral extract RR 4.50, 95% CI 2.29 to 8.86) or eradicating
      mucositis (allopurinol RR 19.00, 95% CI 1.17 to 307.63). Three of these trials
      were rated as at moderate risk of bias and one as at high risk of bias. The
      following agents were not found to be effective: benzydamine HCl, sucralfate,
      tetrachlorodecaoxide, chlorhexidine and 'magic' (lidocaine solution,
      diphenhydramine hydrochloride and aluminum hydroxide suspension). Six trials
      compared the time to heal and mucositis was found to heal more quickly with two
      interventions: granulocyte macrophage-colony stimulating factor when compared to
      povidone iodine, with mean difference -3.5 days (95% CI -4.1 to -2.9) and
      allopurinol compared to placebo, with mean difference -4.5 days (95% CI -5.8 to 
      3.2). Three trials compared patient controlled analgesia (PCA) to the continuous
      infusion method for controlling pain. There was no evidence of a difference,
      however, less opiate was used per hour for PCA, and the duration of pain was
      shorter. One trial demonstrated that pharmacokinetically based analgesia (PKPCA)
      reduced pain compared with PCA: however, more opiate was used with PKPCA.
      AUTHORS' CONCLUSIONS: There is weak and unreliable evidence that allopurinol
      mouthwash, granulocyte macrophage-colony stimulating factor, immunoglobulin or
      human placental extract improve or eradicate mucositis. There is no evidence that
      patient controlled analgesia (PCA) is better than continuous infusion method for
      controlling pain, however, less opiate was used per hour, and duration of pain
      was shorter, for PCA. Further, well designed, placebo-controlled trials assessing
      the effectiveness of allopurinol mouthwash, granulocyte macrophage-colony
      stimulating factor, immunoglobulin, human placental extract, other interventions
      investigated in this review and new interventions for treating mucositis are
      needed.

PMID- 17443515
TI  - Pre-operative radiotherapy and curative surgery for the management of localized
      rectal carcinoma.
AB  - BACKGROUND: Preoperative radiotherapy (PRT) has become part of standard practice
      offered to improve treatment outcomes in patients with rectal cancer. OBJECTIVES:
      To determine if PRT improves outcome for patients with localized resectable
      rectal cancer and how it compared with other adjuvant or neoadjuvant strategies.
      SEARCH STRATEGY: A computerized search was performed December 2006 on MEDLINE
      (from 1966 to December 2006) and the Cochrane Central Register of Controlled
      Trials (CENTRAL), conference proceedings, using MeSH and textwords where
      appropriate to identify randomized trials in PRT and rectal cancer. In addition,
      MetaRegister of Clinical Trials was searched for ongoing trials. SELECTION
      CRITERIA: Randomized trials with a PRT arm versus surgery alone, or other
      neoadjuvant or adjuvant (NA/A) strategies, targeted patients with localized
      rectal cancer planned for radical surgery were included. DATA COLLECTION AND
      ANALYSIS: Trials were selected, data extracted and quality assessed by 2 authors.
      Quality was assessed using a 14 point checklist. Summary statistics included
      Hazard ratios and variances (for the outcomes: overall (OA) mortality, cause
      specific (CS) mortality, any recurrence and local recurrences (LR)) and Odds
      Ratio (OR) for other outcomes. Potential sources of heterogeneity hypothesized a
      priori included study quality, biological effective dose (BED), radiotherapy RT
      technique, and total mesorectal excision (TME) surgery. MAIN RESULTS: Nineteen
      trials compared PRT versus surgery alone. Overall (OA) mortality was marginally
      improved HR 0.93 [95% CI -0.87-1](absolute difference is 2% if the expected
      survival rate is 60%). Local recurrence (LR) was improved but the magnitude of
      benefit was heterogeneous across trials. Sensitivity analyses suggested greater
      benefits in patients treated with BED>30Gy(10) and multiple field RT techniques.
      There was significantly more pelvic or perineal wound infection, late rectal and
      sexual dysfunction. Nine trials compared PRT vs. other NA/A. Available evidence
      did not support an OA mortality or sphincter preserving benefit with the use of
      combined chemoradiotherapy (CRT) or selective postoperative RT. CRT provides
      incremental benefit for local control compared with PRT, which was independent of
      the timing of the CT. There was no significant difference in outcome for
      different intervals between RT and surgery (2 vs. 8 wk). Dose escalation with
      endocavitary boost showed significant effect on sphincter preservation. AUTHORS'
      CONCLUSIONS: Optimal PRT improves LR, OA mortality, but no increase in sphincter
      sparing procedure. CRT further increases local control. If the objective is to
      increase the incidence of sphincter sparing surgery, endocavitary boost showed
      the most promise. Strategies with the potential to improve outcomes, especially
      OAS and sphincter sparing while reducing acute and late toxicities (rectal and
      sexual function) are needed to guide future strategy designs.

PMID- 17443516
TI  - Effectiveness of intermediate care in nursing-led in-patient units.
AB  - BACKGROUND: The Nursing led inpatient Unit (NLU) is one of a range of services
      that have been considered in order to manage more successfully the transition
      between hospital and home for patients with extended recovery times. This is an
      update of an earlier review published in The Cochrane Library in Issue 3, 2004.
      OBJECTIVES: To determine whether nursing-led inpatient units are effective in
      preparing patients for discharge from hospital compared to usual inpatient care.
      SEARCH STRATEGY: We searched The Cochrane Library, the Specialized Register of
      the Cochrane Effective Practice and Organisation of Care (EPOC) group, MEDLINE,
      CINAHL, EMBASE, BNI and HMIC databases. Citation searches were undertaken on the
      science and social science citation indices. Authors were contacted to identify
      additional data. The initial search was done in January 2001. The register search
      was updated in October 2006, the other database searches were updated in November
      2006 and the citation search was run in January 2007. SELECTION CRITERIA:
      Controlled trials and interrupted time series designs that compared the NLU to
      usual inpatient care managed by doctors. Patients over 18 years of age following
      an acute hospital admission for a physical health condition. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently extracted data and assessed study quality.
      MAIN RESULTS: Ten random or quasi-random controlled trials reported on a total of
      1896 patients. There was no statistically significant effect on inpatient
      mortality (OR 1.10, 95% CI 0.56 to 2.16) or mortality to longest follow up (OR
      0.92, 95% CI 0.65 to 1.29) but higher quality studies showed a larger non
      significant increase in inpatient mortality (OR 1.52, 95% CI 0.86 to 2.68).
      Discharge to institutional care was reduced for the NLU (OR 0.44 95% CI 0.22 to
      0.89) and functional status at discharge increased (SMD 0.37, 95% CI 0.20 to
      0.54) but there was a near significant increase in inpatient stay (WMD 5.13 days
      95% CI -0.5 days to 10.76 days). Early readmissions were reduced (OR 0.52 95% CI
      0.34 to 0.80). One study compared a NLU for the chronically critically ill with
      ICU care. Mortality (OR 0.62 95% CI 0.35 to 1.10) and length of inpatient stay
      differ did not differ (WMD 2 days, 95% CI 10.96 to -6.96 days). Early
      readmissions were reduced (OR 0.33 95% CI 0.12 to 0.94). Costs of care on the NLU
      were higher for UK studies but lower for US based studies. AUTHORS' CONCLUSIONS:
      There is some evidence that patients discharged from a NLU are better prepared
      for discharge but it is unclear if this is simply a product of an increased
      length of inpatient stay. No statistically significant adverse effects were noted
      but the possibility of increased early mortality cannot be discounted. More
      research is needed.

PMID- 17443517
TI  - Intravenous magnesium for acute myocardial infarction.
AB  - BACKGROUND: Mortality and morbidity from acute myocardial infarction (AMI) remain
      high. Intravenous magnesium started early after the onset of AMI is thought to be
      a promising adjuvant treatment. Conflicting results from earlier trials and meta
      analyses warrant a systematic review of available evidence. OBJECTIVES: To
      examine the effect of intravenous magnesium versus placebo on early mortality and
      morbidity. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library Issue 3,
      2006), MEDLINE (January 1966 to June 2006) and EMBASE (January 1980 to June
      2006), and the Chinese Biomedical Disk (CBM disk) (January 1978 to June 2006).
      Some core Chinese medical journals relevant to the cardiovascular field were hand
      searched from their starting date to the first-half year of 2006. SELECTION
      CRITERIA: All randomized controlled trials that compared intravenous magnesium
      with placebo in the presence or absence of fibrinolytic therapy in addition to
      routine treatment were eligible if they reported mortality and morbidity within
      35 days of AMI onset. DATA COLLECTION AND ANALYSIS: Two reviewers independently
      assessed the trial quality and extracted data using a standard form. Odds ratio
      (OR) were used to pool the effect if appropriate. Where heterogeneity of effects
      was found, clinical and methodological sources of this were explored. MAIN
      RESULTS: For early mortality where there was evidence of heterogeneity, a fixed
      effect meta-analysis showed no difference between magnesium and placebo groups
      (OR 0.99, 95%CI 0.94 to 1.04), while a random-effects meta-analysis showed a
      significant reduction comparing magnesium with placebo (OR 0.66, 95% CI 0.53 to
      0.82). Stratification by timing of treatment (< 6 hrs, 6+ hrs) reduced
      heterogeneity, and in both fixed-effect and random-effects models no significant
      effect of magnesium was found. In stratified analyses, early mortality was
      reduced for patients not treated with thrombolysis (OR=0.73, 95% CI 0.56 to 0.94
      by random-effects model) and for those treated with less than 75 mmol of
      magnesium (OR=0.59, 95% CI 0.49 to 0.70) in the magnesium compared with placebo
      groups.Meta-analysis for the secondary outcomes where there was no evidence of
      heterogeneity showed reductions in the odds of ventricular fibrillation (OR=0.88,
      95% CI 0.81 to 0.96), but increases in the odds of profound hypotension (OR=1.13,
      95% CI 1.09 to 1.19) and bradycardia (OR=1.49, 95% CI 1.26 to 1.77) comparing
      magnesium with placebo. No difference was observed for heart block (OR=1.05, 95%
      CI 0.97-1.14). For those outcomes where there was evidence of heterogeneity, meta
      analysis with both fixed-effect and random-effects models showed that magnesium
      could decrease ventricular tachycardia (OR=0.45, 95% CI 0.31 to 0.66 by fixed
      effect model; OR=0.40, 95% CI 0.19 to 0.84 by random-effects model) and severe
      arrhythmia needing treatment or Lown 2-5 (OR=0.72, 95% CI 0.60 to 0.85 by fixed
      effect model; OR=0.51, 95% CI 0.33 to 0.79 by random-effects model) compared with
      placebo. There was no difference on the effect of cardiogenic shock between the
      two groups. AUTHORS' CONCLUSIONS: Owing to the likelihood of publication bias and
      marked heterogeneity of treatment effects, it is essential that the findings are
      interpreted cautiously. From the evidence reviewed here, we consider that: (1) it
      is unlikely that magnesium is beneficial in reducing mortality both in patients
      treated early and in patients treated late, and in patients already receiving
      thrombolytic therapy; (2) it is unlikely that magnesium will reduce mortality
      when used at high dose (>=75 mmol); (3) magnesium treatment may reduce the
      incidence of ventricular fibrillation, ventricular tachycardia, severe arrhythmia
      needing treatment or Lown 2-5, but it may increase the incidence of profound
      hypotension, bradycardia and flushing; and (4) the areas of uncertainty regarding
      the effect of magnesium on mortality remain the effect of low dose treatment (<
      75 mmol) and in patients not treated with thrombolysis.

PMID- 17443518
TI  - Effects of nonsteroidal anti-inflammatory drugs on postoperative renal function
      in adults with normal renal function.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) can play a major role
      in the management of acute pain in the peri-operative period. However, there are
      conflicting views on whether NSAIDs are associated with adverse renal effects.
      OBJECTIVES: The primary objective of this review was to determine the effects of
      NSAIDs on postoperative renal function in adults with normal preoperative renal
      function. SEARCH STRATEGY: Electronic searches for relevant randomised and quasi
      randomised controlled trials in Cochrane Central Register of Controlled Trials,
      MEDLINE and EMBASE were performed. Attempts were also made to identify trials
      from citation lists of relevant trials, review articles and clinical practice
      guidelines. Handsearching of conference abstracts published in major anaesthetic
      journals was also performed. Date of most recent search: May 2006 SELECTION
      CRITERIA: The inclusion criteria were randomised or quasi-randomised comparisons
      of individual NSAIDs with either each other or placebo for treatment of
      postoperative pain, with relevant postoperative renal outcome measures, in adult
      surgical patients with normal renal function. DATA COLLECTION AND ANALYSIS: The
      data were extracted independently by two authors. The primary outcome measure was
      creatinine clearance within the first two days after surgery. Secondary outcome
      measures included serum creatinine, urine volume, urinary sodium level, urinary
      potassium level, fractional excretion of sodium, fractional excretion of
      potassium and need for dialysis. Weighted mean differences for continuous
      outcomes and relative risk (RR) and risk difference (RD) for dichotomous outcomes
      were estimated with 95% confidence intervals (CI). MAIN RESULTS: Twenty-three
      trials (1459 patients) fulfilled the selection criteria for this review. NSAIDs
      reduced creatinine clearance by 16 mL/min (95%CI 5 to 28) and potassium output by
      38 mmol/day (95%CI 19 to 56) on the first day after surgery compared to placebo.
      There was no significant difference in serum creatinine on the first day (0
      umol/L, 95%CI -3 to 4) compared to placebo. No significant reduction in urine
      volume during the early postoperative period was found. There was no significant
      difference in serum creatinine in the early postoperative period between patients
      receiving diclofenac, ketorolac, indomethacin, ketoprofen or etodolac. No cases
      of postoperative renal failure requiring dialysis were described. The trials were
      not heterogeneous for the primary outcome. AUTHORS' CONCLUSIONS: NSAIDs caused a
      clinically unimportant transient reduction in renal function in the early
      postoperative period in patients with normal preoperative renal function. NSAIDs
      should not be withheld from adults with normal preoperative renal function
      because of concerns about postoperative renal impairment.

PMID- 17443519
TI  - Screening for abdominal aortic aneurysm.
AB  - BACKGROUND: Abdominal aortic aneurysm (AAA) is found in 5% to 10% of men aged 65
      to 79 years. The major complication is rupture which presents as a surgical
      emergency. The mortality after rupture is high, 80% for patients reaching
      hospital and 50% for those undergoing surgery for emergency repair. Currently
      elective surgical repair is recommended for aneurysms discovered to be larger
      than 5.5 cm to prevent rupture. There is interest in population screening to
      detect, monitor and repair abdominal aortic aneurysms before rupture. OBJECTIVES:
      To determine the effects of screening asymptomatic individuals for AAA on
      mortality, subsequent treatment, quality of life and cost effectiveness of
      screening. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group
      searched their Trials Register (last searched 26 January 2007) and CENTRAL (last
      searched Issue 1, 2007). SELECTION CRITERIA: Randomised controlled trials of
      population screening for AAA. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trials and extracted data. MAIN RESULTS: Four studies
      involving 127,891 men and 9,342 women were included in this review. Only one
      study included women. Results for men and women were analysed separately. Three
      to five years after screening there was no significant difference in all-cause
      mortality between screened and unscreened groups for men or women (men, odds
      ratio (OR) 0.95; 95% Confidence interval (CI) 0.85 to 1.07; for women OR 1.06;
      95% CI 0.93 to 1.21). There was a significant decrease in mortality from AAA in
      men (OR 0.60; 95% CI 0.47 to 0.78), but not for women (OR 1.99; 95% CI 0.36 to
      10.88). In this analysis mortality includes death from rupture and from emergency
      or elective surgery for aneurysm repair. There was also a decreased incidence of
      ruptured aneurysm in men (OR 0.45; 95% CI 0.21 to 0.99) but not in women (OR
      1.49; 95% CI 0.25 to 8.94). There was a significant increase in surgery for AAA
      in men (OR 2.03; 95% CI 1.59 to 2.59). This was not reported in women. There were
      no data on life expectancy, complications of surgery or subjective quality of
      life. AUTHORS' CONCLUSIONS: There is evidence of a significant reduction in
      mortality from AAA in men aged 65 to 79 years who undergo ultrasound screening.
      There is insufficient evidence to demonstrate benefit in women. The cost
      effectiveness may be acceptable, but needs further expert analysis. These
      findings need careful consideration in judging whether a co-ordinated population
      based screening programme should be introduced.

PMID- 17443520
TI  - Inhaled corticosteroids for stable chronic obstructive pulmonary disease.
AB  - BACKGROUND: The role of inhaled corticosteroids (ICS) in chronic obstructive
      pulmonary disease (COPD) has been the subject of much controversy. Major
      international guidelines recommend selective use of ICS. Recently published meta
      analyses have reported conflicting findings on the effects of inhaled steroid
      therapy in COPD. OBJECTIVES: The objective of the review is to determine the
      efficacy of regular use of inhaled corticosteroids in patients with stable COPD.
      SEARCH STRATEGY: A pre-defined search strategy was used to search the Cochrane
      Airways Group specialised register for relevant literature. Searches are current
      as of October 2006. SELECTION CRITERIA: We selected randomised trials comparing
      any dose of any type of inhaled steroid with a placebo control in patients with
      COPD. Acute bronchodilator reversibility to short term beta2-agonists and
      bronchial hyperresponsiveness were not exclusion criteria. The a priori primary
      outcome was change in lung function. Data on mortality, exacerbations, quality of
      life and symptoms, rescue bronchodilator use, exercise capacity, biomarkers and
      safety were also analysed. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trial quality and extracted data. Study authors were
      contacted for additional information. Adverse effects information was collected
      from the trials. MAIN RESULTS: Forty-seven primary studies with 13,139
      participants met the inclusion criteria. Medium term use of ICS (> two months and
      up to six months) resulted in a small improvement in FEV1 in some studies. Long
      term use of ICS (> six months) did not significantly reduce the rate of decline
      in FEV1 in COPD patients (weighted mean difference (WMD) 5.80 ml/year with ICS
      over placebo, 95% CI -0.28 to 11.88, 2333 participants). There was no
      statistically significant effect on mortality in COPD patients (OR 0.98, 95% CI
      0.83 to 1.16, 8390 participants). Long term use of ICS reduced the mean rate of
      exacerbations in those studies where pooling of data was possible (WMD -0.26
      exacerbations per patient per year, 95% CI -0.37 to -0.14, 2586 participants).
      ICS slowed the rate of decline in quality of life, as measured by the St George's
      Respiratory Questionnaire (WMD -1.22 units/year, 95% CI -1.83 to -0.60, 2507
      participants). Response to ICS was not predicted by oral steroid response,
      bronchodilator reversibility or bronchial hyper-responsiveness in COPD patients.
      There was an increased risk of oropharyngeal candidiasis (OR 2.49, 95% CI 1.78 to
      3.49, 4380 participants) and hoarseness. The few long term studies that measured
      bone effects generally showed no major effect on fractures and bone mineral
      density over 3 years. AUTHORS' CONCLUSIONS: Patients and clinicians should
      balance the potential benefits of inhaled steroids in COPD (reduced rate of
      exacerbations, reduced rate of decline in quality of life), against the known
      increase in local side effects (oropharyngeal candidiasis and hoarseness). The
      risk of long term adverse effects is unknown.

PMID- 17443521
TI  - Traction for low-back pain with or without sciatica.
AB  - BACKGROUND: Traction is used to treat low-back pain (LBP), often with other
      treatments. OBJECTIVES: To determine traction's effectiveness, compared to
      reference treatments, placebo, sham traction or no treatment for LBP. SEARCH
      STRATEGY: We searched CENTRAL (The Cochrane Library 2006, issue 4), MEDLINE,
      EMBASE, and CINAHL to October 2006, references in relevant reviews and personal
      files. SELECTION CRITERIA: Randomized controlled trials (RCTs) involving traction
      to treat acute (less than four weeks duration), sub-acute (four to 12 weeks) or
      chronic (more than 12 weeks) non-specific LBP with or without sciatica. DATA
      COLLECTION AND ANALYSIS: Study selection, methodological quality assessment and
      data extraction were done independently by two authors. As there were
      insufficient data for statistical pooling, we performed a qualitative analysis.
      MAIN RESULTS: We included 25 RCTs (2206 patients; 1045 receiving traction). Five
      trials were considered high quality. For patients with mixed symptom patterns
      (acute, sub-acute and chronic LBP with and without sciatica) there is: strong
      evidence of no statistically significant difference in outcomes between traction
      as a single treatment and placebo, sham or no treatment; moderate evidence that
      traction as a single treatment is no more effective than other treatments;
      limited evidence of no significant difference in outcomes between a standard
      physical therapy program with or without continuous traction. For LBP patients
      with sciatica (with acute, sub-acute or chronic pain), there is conflicting
      evidence in several comparisons: autotraction compared to placebo, sham or no
      treatment; other forms of traction compared to other treatments; different forms
      of traction. In other comparisons, there were no statistically significant
      differences; the evidence is moderate for continuous or intermittent traction
      compared to placebo, sham or no treatment, and limited for light versus normal
      force traction. AUTHORS' CONCLUSIONS:  IMPLICATIONS FOR PRACTICE: The results of
      the available studies involving mixed groups of acute, sub-acute and chronic
      patients with LBP with and without sciatica were quite consistent, indicating
      that continuous or intermittent traction as a single treatment for LBP is not
      likely effective for this group. Traction for patients with sciatica cannot be
      judged effective at present either, due to inconsistent results and
      methodological problems in most studies. We conclude that traction as a single
      treatment for LBP is probably not effective. IMPLICATIONS FOR RESEARCH: Any
      future research on traction for patients with LBP should distinguish between
      symptom pattern and duration, and should be carried out according to the highest
      methodological standards.

PMID- 17443522
TI  - Treatments for iron-deficiency anaemia in pregnancy.
AB  - BACKGROUND: Iron deficiency, the most common cause of anaemia in pregnancy
      worldwide, can be mild, moderate or severe. Severe anaemia can have very serious
      consequences for mothers and babies, but there is controversy about whether
      treating mild or moderate anaemia provides more benefit than harm. OBJECTIVES: To
      assess the effects of different treatments for iron-deficiency anaemia in
      pregnancy (defined as haemoglobin less than 11 g/dl) on maternal and neonatal
      morbidity and mortality. SEARCH STRATEGY: We searched the Cochrane Pregnancy and
      Childbirth Group's Trials Register (January 2007), the Cochrane Central Register
      of Controlled Trials (The Cochrane Library 2005, Issue 4), MEDLINE (1966 to
      December 2005), EMBASE (1976 to December 2005), LILACS (1982 to 40 edition),
      BIOSIS Previews (1980 to June 2002) and ongoing clinical trial registers.
      SELECTION CRITERIA: Randomised controlled trials comparing treatments for iron
      deficiency anaemia in pregnancy. DATA COLLECTION AND ANALYSIS: We identified 17
      trials, involving 2578 women. We assessed trial quality. MAIN RESULTS: The trials
      were small and generally methodologically poor. They covered a very wide range of
      differing drugs, doses and routes of administration, making it difficult to pool
      data. Oral iron in pregnancy showed a reduction in the incidence of anaemia (one
      trial, 125 women; relative risk 0.38; 95% confidence interval 0.26 to 0.55). It
      was not possible to assess the effects of treatment by severity of anaemia. A
      trend was found between dose and reported adverse effects. We found that most
      trials had no assessments on relevant clinical outcomes and a paucity of data on
      adverse effects, including some that are known to be associated with iron
      administration. Although the intramuscular and intravenous routes produced better
      haematological indices in women than the oral route, no clinical outcomes were
      assessed and there were insufficient data on adverse effects, for example, on
      venous thrombosis and severe allergic reactions. AUTHORS' CONCLUSIONS: Despite
      the high incidence and burden of disease associated with this condition, there is
      a paucity of good quality trials assessing clinical maternal and neonatal effects
      of iron administration in women with anaemia. Daily oral iron treatment improves
      haematological indices but causes frequent gastrointestinal adverse effects.
      Parenteral (intramuscular and intravenous) iron enhances haematological response,
      compared with oral iron, but there are concerns about possible important adverse
      effects. Large, good quality trials, assessing clinical outcomes (including
      adverse effects) are required.

PMID- 17443523
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: Trials were identified on 10 October 2006
      through a search of the Cochrane Dementia and Cognitive Improvement Group's
      Specialized Register which contains records from all main medical databases
      (MEDLINE, EMBASE, CINAHL, PsycINFO, SIGLE, LILACS), from ongoing trials databases
      such as Clinicaltrials.gov and Current Controlled Trials and many other sources.
      The search terms used were ginkgo*, tanakan, EGB-761, EGB761, "EGB 761" and
      gingko*. 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: Clinical global improvement as assessed by the physician, was
      dichotomized between participants who showed improvement or were unchanged and
      those who were worse. There are benefits associated with Ginkgo (dose greater
      than 200 mg/day) at 24 weeks (207/276 compared with 178/273, OR 1.66, 95% CI 1.12
      to 2.46, P=.001) (2 studies), but not for the lower dose. Cognition shows benefit
      for Ginkgo (any dose) at 12 weeks (SMD -0.65, 95% CI -1.22 to -0.09 P=0.02, 5
      studies) but not at 24 weeks. Five studies assessed activities of daily living
      (ADLs), using different scales. Some scales are more comprehensive than just
      ADLs. The results show benefit for Ginkgo (dose less than 200 mg/day) compared
      with placebo at 12 weeks (MD -5.0, 95% CI -7.88, -2.12, p=0.0007, one study), and
      at 24 weeks (SMD -0.16, 95% CI -0.31 to -0.01, p=0.03, 3 studies) but there are
      no differences at the higher dose. No study assessed mood and function
      separately, but one study used the ADAS-Noncog, which assesses function over
      several domains, but not cognitive function. There was no difference between
      Ginkgo and placebo. There are no significant differences between Ginkgo and
      placebo in the proportion of participants experiencing adverse events. There are
      no data available on Quality of Life, measures of depression or dependency.
      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 we cannot exclude publication bias. The evidence that
      Ginkgo has predictable and clinically significant benefit for people with
      dementia or cognitive impairment is inconsistent and unconvincing.

PMID- 17443524
TI  - Medical treatments in the short term management of reflux oesophagitis.
AB  - BACKGROUND: Oesophagitis arises when reflux of acid from the stomach into the
      oesophagus causes mucosal inflammation. It is a common problem and a systematic
      review on the optimum treatment would be useful. OBJECTIVES: To assess the
      effectiveness of proton pump inhibitors (PPIs), H2 receptor antagonists (H2RAs),
      prokinetic therapy, sucralfate and placebo in healing oesophagitis or curing
      reflux symptoms or both. To compare adverse effects with the different
      treatments. SEARCH STRATEGY: We searched MEDLINE, EMBASE, CINAHL, Cochrane
      Central Register of Controlled Trials and the National Research Register until
      December 2004 and reference lists of articles. We also contacted manufacturers
      and researchers in the field. SELECTION CRITERIA: Randomised controlled trials
      assessing the healing of oesophagitis or reflux symptoms or both. Treatment
      involving PPIs, H2RAs, prokinetics, sucralfate and combinations either in
      comparison to another treatment regimen or to placebo for 2 and 12 weeks. DATA
      COLLECTION AND ANALYSIS: Two reviews independently assessed trial quality and
      extracted data. MAIN RESULTS: We included 134 trials involving 35,978
      oesophagitis participants. Five RCTs evaluated standard dose of PPI versus
      placebo in 965 participants. There was a statistically significant benefit of
      taking standard dose PPI therapy compared to placebo in healing of oesophagitis
      (RR = 0.22; 95% CI 0.15 to 0.31). Ten RCTs reported on the outcome for H2RA
      versus placebo evaluating 1241 participants. There was statistically significant
      benefit of taking H2RA compared to placebo in healing of oesophagitis (RR
      0.74,95% CI = 0.66 to 0.84). Three RCTs evaluated prokinetic therapy versus
      placebo in 198 participants. There was no statistically significant benefit of
      taking prokinetic therapy compared to placebo in healing of oesophagitis (RR
      0.71, 95% CI 0.46 to 1.10). Twenty six RCTs reported the outcome for PPI versus
      H2RA or H2RA plus prokinetics, evaluating 4032 participants. There was
      statistically significant benefit of taking PPI therapy compared to H2RA or H2RA
      plus prokinetics in healing of oesophagitis (RR 0.51, 95% CI 0.44 to 0.59).
      AUTHORS' CONCLUSIONS: PPI therapy is the most effective therapy in oesophagitis
      but H2RA therapy is also superior to placebo. There is a paucity of evidence on
      prokinetic therapy but no evidence that it is superior to placebo.

PMID- 17443525
TI  - Conservative treatments for whiplash.
AB  - BACKGROUND: Many treatments are available for whiplash patients but there is
      little scientific evidence for their accepted use. Patients with whiplash
      associated disorders (WAD) can be classified by the severity of signs and
      symptoms from Grade 0 (no complaints or physical signs) to Grade 4 (fracture or
      dislocation). OBJECTIVES: To assess the effectiveness of conservative treatment
      for patients with whiplash injuries rated as Grades 1 or 2 (neck and
      musculoskeletal complaints). SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (The Cochrane Library, 2006, Issue 3), MEDLINE,
      CINAHL, PsycINFO, and PEDro to November 2006 and screened references of
      identified randomised trials and relevant systematic reviews. SELECTION CRITERIA:
      We selected randomised controlled trials published in English, French, German or
      Dutch, that included patients with a whiplash-injury, conservative interventions,
      outcomes of pain, global perceived effect or participation in daily activities.
      DATA COLLECTION AND ANALYSIS: Two authors independently assessed the
      methodological quality using the Delphi criteria and extracted the data onto
      standardised data-extraction forms. We did not pool the results because of the
      heterogeneity of the population, intervention and outcomes and lack of data. A
      pre-planned stratified analysis was performed for three different comparisons.
      MAIN RESULTS: Twenty-three studies (2344 participants) were included in this
      update, including nine new studies. A broad variety of conservative interventions
      were evaluated. Two studies included patients with chronic symptoms (longer than
      three months), two included subacute (four to six weeks) symptoms, two had
      undefined duration of symptoms, and 17 studied patients with acute (less than
      three weeks) symptoms. Only eight studies (33.3%) satisfied one of our criteria
      of high quality, indicating overall, a poor methodological quality. Interventions
      were divided into passive (such as rest, immobilisation, ultrasound, etc) and
      active interventions (such as exercises, act as usual approach, etc.) and were
      compared with no treatment, a placebo or each other. Clinical and statistical
      heterogeneity and lack of data precluded pooling. Individual studies demonstrated
      effectiveness of one treatment over another, but the comparisons were varied and
      results inconsistent. Therefore, the evidence neither supports nor refutes the
      effectiveness of either passive or active treatments to relieve the symptoms of
      WAD, Grades 1 or 2. AUTHORS' CONCLUSIONS: The current literature is of poor
      methodological quality and is insufficiently homogeneous to allow the pooling of
      results. Therefore, clearly effective treatments are not supported at this time
      for the treatment of acute, subacute or chronic symptoms of whiplash-associated
      disorders.

PMID- 17443526
TI  - Treatment of vaginal bleeding irregularities induced by progestin only
      contraceptives.
AB  - BACKGROUND: Despite their high effectiveness, progestin-only contraceptives are
      considered less than ideal by the many women who experience disruption of their
      normal vaginal bleeding pattern when using these methods. Current treatments to
      control these bleeding irregularities are not sufficiently effective. OBJECTIVES:
      We evaluated preventive and therapeutic interventions of bleeding irregularities
      associated with the use of progestin-only contraceptives. SEARCH STRATEGY:
      Literature was identified through database searches, reference lists,
      organisations and individuals, covering the period until December 2006. SELECTION
      CRITERIA: Trials with random or alternate allocation, testing interventions for
      the prevention or treatment of bleeding irregularities associated with the use of
      progestin-only contraceptives were eligible. DATA COLLECTION AND ANALYSIS:
      Results are expressed as relative risks (RR) with 95 % confidence interval (CI)
      for categorical data and as weighted mean difference (WMD) with 95 % CI for
      continuous data. When we encountered heterogeneity (visual or statistical) we
      used the random-effects model (quantitative) or did not produce a summary
      estimate (qualitative). MAIN RESULTS: 19 Randomised controlled trials including
      2290 participants were included. Over 60% of these trials had low to moderate
      risk of bias. Estrogen treatments reduced the number of days of an ongoing
      bleeding episode in DMPA users and had a positive therapeutic effect in Norplant
      users. However, treatment frequently led to discontinuation due to
      gastrointestinal upset. Combinations of oral ethinyl estradiol and levonorgestrel
      taken by Norplant users experiencing bleeding irregularities, improved bleeding
      patterns but method discontinuation rates remained the same. Norplant users
      administered the anti-progestin mifepristone therapeutically reported fewer days
      of bleeding than those given placebo. Prophylactic oral mifepristone used monthly
      by new Norplant users reduced bleeding, when compared to placebo.Ibuprofen was
      reported to decrease the length of bleeding episodes over a year, but the data
      were not presented in a suitable format for our analysis. Mefenamic acid reduced
      continued irregular bleeding during treatment in Norplant users, but not among
      DMPA users. Vitamin E and aspirin had no effect on bleeding patterns in a large
      trial of women using Norplant. Norplant users receiving tamoxifen had less
      unacceptable bleeding after treatment and were more likely to continue using
      Norplant than those receiving placebo. AUTHORS' CONCLUSIONS: Some women may
      benefit from the interventions described, particularly with cessation of an
      ongoing bleeding episode. Several regimens offer promise in regulating bleeding,
      but findings need to be reproduced in larger scale trials. Intermittent treatment
      with an agent may help some women to continue the use of a progestin-only
      contraceptive. The results of this review do not support routine clinical use of
      any of the regimens included in the trials, particularly for long-term effect.

PMID- 17443527
TI  - Prolonged versus short course of indomethacin for the treatment of patent ductus
      arteriosus in preterm infants.
AB  - BACKGROUND: Indomethacin is a prostaglandin inhibitor used to treat patent ductus
      arteriosus (PDA) in preterm infants. Although indomethacin produces ductal
      closure in the majority of cases, it is ineffective in up to 40% of patients.
      Furthermore, the ductus will re-open in up to 35% of infants who initially
      respond to the drug. Prolonging the course of indomethacin has the potential to
      achieve higher rates of ductal closure. OBJECTIVES: To determine the effect of a
      prolonged course of indomethacin (compared to a short course) on the rate of
      treatment failure without unwanted side-effects in preterm infants with PDA.
      SEARCH STRATEGY: The search included review of personal files, abstracts of
      conferences, and the following electronic databases: MEDLINE (1966 to December
      2006), EMBASE (1974 to December 2006), and Oxford Database of Perinatal Trials,
      Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4,
      2006). No language restrictions were applied. SELECTION CRITERIA: Randomized or
      quasi-randomized controlled trials including preterm infants with PDA, diagnosed
      on clinical and/or echocardiographic examination that evaluated indomethacin
      treatment by any route given as a long course (four or more doses) vs. a short
      course (three or fewer doses) were included in the review. Trials needed to
      report on at least one of the following outcomes: failure of PDA to close, need
      for re-treatment, PDA re-opening, PDA ligation, mortality, duration of assisted
      ventilation, chronic lung disease (CLD), duration of supplemental oxygen
      dependence, intraventricular hemorrhage (IVH) (all and severe), diminished urine
      output, increased serum creatinine, necrotizing enterocolitis (NEC), bleeding
      diathesis, retinopathy of prematurity (ROP), and duration of hospital stay. DATA
      COLLECTION AND ANALYSIS: The three review authors independently abstracted data
      from each study. Relative risk (RR) and Risk Difference (RD) with 95% confidence
      intervals (CI) using the fixed effect model for meta-analysis are reported. When
      a statistically significant RD was found, the number needed to treat (NNT) or
      number needed to harm (NNH) was also calculated with 95% CIs. The I squared
      statistic was used to test for heterogeneity of results among included trials.
      MAIN RESULTS: Five trials met inclusion criteria and included 431 infants.
      Prolonged indomethacin treatment when compared to the short course did not result
      in a statistically significant difference in PDA closure, re-treatment, re
      opening, or ligation rates. The prolonged course was associated with an increased
      risk of NEC [typical RR 1.87 (95% CI 1.07, 3.27); typical RD 0.08 (95% CI 0.01,
      0.15); NNH 13 (7, 100)] and a decreased incidence of renal function impairment,
      as evidenced by a lower proportion of infants having diminished urine output
      [typical RR 0.27 (95% CI 0.13, 0.6); typical RD -0.19 (95% CI -0.28, -0.09); NNT
      5 (4, 11)] and increased serum creatinine level [typical RR 0.51 (95% CI 0.33,
      0.77); typical RD -0.14 (95% CI -0.23, -0.06); NNT 7 (4, 16)]. AUTHORS'
      CONCLUSIONS: Implications for practiceProlonged indomethacin course does not
      appear to have a significant effect on improving important outcomes, such as PDA
      treatment failure, CLD, IVH, or mortality. The reduction of transient renal
      impairment does not outweigh the increased risk of NEC associated with the
      prolonged course. Based on these results, a prolonged course of indomethacin
      cannot be recommended for the routine treatment of PDA in preterm infants.
      Implications for researchThere is a paucity of data on optimal dosing and
      duration of indomethacin therapy for the treatment of PDA, in particular for
      extremely low birth weight infants (ELBW) premature infants. It is likely that a
      single standard indomethacin regime is not the ideal for every premature infant.
      Therefore, individual patient response should be considered and evaluated, in
      particular in ELBW infants. Future randomized clinical trials should include this
      high risk population and investigate the effect of tailoring dose and duration of
      therapy to individual response in terms of echocardiographic findings and/or
      prostaglandin levels, focusing on clinically significant outcomes, including long
      term neurodevelopmental outcomes. In addition, factors that may influence
      treatment effect, such as birth weight, gestational age, age at the time of
      randomization, total fluid intake, feeding practice, and severity of PDA, need to
      be taken into account when designing such studies.

PMID- 17443528
TI  - Cognitive rehabilitation for spatial neglect following stroke.
AB  - BACKGROUND: Unilateral spatial neglect causes difficulty attending to one side of
      space. Various rehabilitation strategies have been used but evidence of their
      benefit is lacking. OBJECTIVES: To determine the persisting effects of cognitive
      rehabilitation specifically aimed at spatial neglect following stroke, as
      measured on impairment and disability level outcome assessments and on
      destination on discharge from hospital. SEARCH STRATEGY: We searched the Cochrane
      Stroke Group Trials Register (last searched 4 July 2005), MEDLINE (1966 to July
      2005), EMBASE (1980 to July 2005), CINAHL (1983 to July 2005), PsycINFO (1974 to
      July 2005), UK National Research Register (July 2005). We handsearched relevant
      journals, screened reference lists, and tracked citations using SCISEARCH.
      SELECTION CRITERIA: We included randomised controlled trials of cognitive
      rehabilitation specifically aimed at spatial neglect. We excluded studies of
      general stroke rehabilitation and studies with mixed patient groups, unless more
      than 75% of their sample were stroke patients or separate stroke data were
      available. DATA COLLECTION AND ANALYSIS: Two review authors independently
      selected trials, extracted data, and assessed trial quality. MAIN RESULTS: We
      included 12 RCTs with 306 participants. Only four had adequate allocation
      concealment, that is a low risk of selection bias. A large number of outcome
      measures were reported. Only six studies measured disability and two investigated
      whether the effects persisted. The overall effect (standardised mean difference)
      on disability had a wide confidence interval that included zero and was not
      statistically significant. For discharge destination there were clinically
      significant effects but in both directions and the confidence interval of the
      odds ratio included one. In contrast, cognitive rehabilitation did improve
      performance on some, but not all, standardised neglect tests. The number of
      cancellation errors made was reduced and the ability to find the midpoint of a
      line improved immediately and persisted at follow up. These effects appeared
      likely to generalise from the samples studied to the target population, but were
      based on a small number of studies. AUTHORS' CONCLUSIONS: Several types of
      neglect specific approaches are now described but there is insufficient evidence
      to support or refute their effectiveness at reducing disability and improving
      independence. They can alter test performance and warrant further investigation
      in high quality randomised controlled trials. As we did not review whether
      patients with neglect benefit from rehabilitation input in general, such patients
      should continue to receive general stroke rehabilitation services.

PMID- 17443529
TI  - Cancer genetic risk assessment for individuals at risk of familial breast cancer.
AB  - BACKGROUND: The recognition of an inherited component to breast cancer has led to
      an increase in demand for information, reassurance, and genetic testing,
      resulting in the creation of genetics clinics for familial cancer. The first step
      for patients referred to a cancer genetic clinic is a risk assessment.
      OBJECTIVES: To evaluate the impact of cancer genetic risk assessment services on
      patients at risk of familial breast cancer. SEARCH STRATEGY: The specialised
      register maintained by the Cochrane Breast Cancer Group was searched. We also
      searched MEDLINE, EMBASE, CINAHL, PsycLIT, CENTRAL, DARE, ASSIA, Web of Science,
      SIGLE and LILACS. The searches covered the period 1985 to February 2005. We also
      hand-searched relevant journals. SELECTION CRITERIA: Trials looking at
      interventions for cancer genetic risk assessment delivery for familial breast
      cancer were considered for inclusion. Trials assessed outcomes such as
      understanding of risk, satisfaction and psychological well-being. Studies were
      excluded if they concerned cancers other than breast cancer or if participants
      were not at risk of breast cancer. Trials concerning the provision of information
      or education were also excluded as it was intended to review these separately.
      Participants could be individuals of any age or gender, with or without a known
      BRCA mutation, but without a previous history of breast cancer or any other
      serious illness. DATA COLLECTION AND ANALYSIS: Two authors independently assessed
      trial quality and extracted data. Additional information was sought from
      investigators as necessary. Due to the heterogeneity of both the interventions
      and outcomes, data were analysed descriptively. MAIN RESULTS: Fifty-eight papers
      were identified as relevant to the review, 54 of these were subsequently
      excluded. The three included trials (pertaining to five papers), provide data on
      1251 participants and assessed the impact of cancer genetic risk assessment on
      outcomes including perceived risk, and psychological distress. This review
      suggests that cancer genetic risk assessment services help to reduce distress,
      improve the accuracy of the perceived risk of, and increase knowledge about,
      breast cancer and genetics. The health professional delivering the risk
      assessment does not appear to have a significant impact on these outcomes.
      AUTHORS' CONCLUSIONS: This review found favourable outcomes for patients' risk
      assessment for familial breast cancer. However, there were too few papers to make
      any significant conclusions about how best to deliver cancer genetic risk
      assessment services. Further research is needed assessing the best means of
      delivering cancer risk assessment, by different health professionals, in
      different ways and in alternative locations.

PMID- 17443530
TI  - Bed rest for acute uncomplicated myocardial infarction.
AB  - BACKGROUND: Bed rest is prescribed to all patients with acute myocardial
      infarction (AMI), but to a variable extent. Current guidelines (American College
      of Cardiology/ American Heart Association) recommend at least 12 hours bed rest
      in patients with uncomplicated ST-elevation myocardial infarction, however the
      basis for this recommendation is unclear. OBJECTIVES: To compare the effects of
      short versus longer bed rest in patients with uncomplicated AMI. SEARCH STRATEGY:
      We searched the Cochrane Central Register of Controlled Trials (The Cochrane
      Library, Issue 2, 2005), MEDLINE (January 1966 - August 2005), EMBASE (January
      1988 - August 2005), PASCAL BioMed (January 1996 - August 2005); PsycINFO
      (January 1966 - August 2005) and BIOSIS Previews (January 1990 - August 2005).
      SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of short
      versus longer bed rest in patients with uncomplicated AMI were sought. DATA
      COLLECTION AND ANALYSIS: Study selection was performed independently by at least
      two investigators according to the predefined inclusion criteria. Data were
      extracted by two investigators independently and in duplicate. Authors were
      contacted to obtain missing information. MAIN RESULTS: We found 15 trials with
      1487 patients assigned to a short period of bed rest (median 6 days) and 1471
      patients assigned to longer bed rest (median 13 days). Generally the studies were
      outdated and appeared to be of moderate to poor methodological reporting quality.
      There was no evidence that shorter bed rest was more harmful than longer bed rest
      in terms of all cause mortality (RR=0.85 (95%CI 0.68 to 1.07), cardiac mortality
      (RR=0.81 (95%CI 0.54 to 1.19), or reinfarction (RR=1.07 (95%CI 0.79 to 1.44)).
      AUTHORS' CONCLUSIONS: Bed rest ranging from 2 to 12 days appears to be as safe as
      longer periods of bed rest. The quality of most trials is unsatisfactory. Current
      bed rest recommendations are not supported by the existing evidence as the
      optimal duration of bed rest is unknown. The lack of adequate trials is
      surprising, considering the large size of several studies to compare
      effectiveness of drugs on people with AMI.

PMID- 17443531
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 test the null hypothesis of no difference in the
      clinical performance between osseointegrated implants loaded at different times 6
      months to 1 year after loading. SEARCH STRATEGY: The Cochrane Oral Health Group's
      Trials Register, The Cochrane Central Register of Controlled Trials, 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 7 August 2006. SELECTION
      CRITERIA: All RCTs of root-form osseointegrated oral implants having a follow up
      of 6 months to 1 year comparing the same osseointegrated root-form oral implants
      immediately (within 1 week); early (between 1 week to 2 months); and
      conventionally loaded (after 2 months). Outcome measures were: prosthesis
      failures, implant failures and marginal bone levels on intraoral radiographs.
      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 Oral Health
      Group's statistical guidelines were followed. MAIN RESULTS: Twenty RCTs were
      identified and 11 trials including 300 patients in total were included. Six
      trials compared immediate versus conventional loading, three early versus
      conventional loading and two immediate versus early loading. 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 when loading the
      implant immediately. 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. Priority
      should be given to trials comparing immediately versus early loaded implants to
      improve patient satisfaction and decrease treatment time. These trials should be
      reported according to the CONSORT guidelines (http://www.consort-statement.org/).

PMID- 17443532
TI  - Rehabilitation interventions for foot drop in neuromuscular disease.
AB  - BACKGROUND: "Foot drop" or "Floppy foot drop" is the term commonly used to
      describe weakness or contracture of the muscles around the ankle joint. It may
      arise from many neuromuscular diseases. OBJECTIVES: To conduct a systematic
      review of randomised trials of treatment for footdrop resulting from
      neuromuscular disease. SEARCH STRATEGY: We searched the Cochrane Neuromuscular
      Disease Group Trials Register (July 2005), MEDLINE (January 1966 to July 2005),
      EMBASE (January 1980 to July 2005), AMED (January 1985 to July 2005) and CINAHL
      databases (January 1982 to July 2005). SELECTION CRITERIA: Randomised and quasi
      randomised trials of physical, orthotic and surgical treatments for footdrop
      resulting from lower motor neuron or muscle disease and related contractures were
      included. People with primary joint disease were excluded. Interventions included
      a 'wait and see' approach, physiotherapy, orthotics, surgery and pharmacological
      therapy. The primary outcome measure was ability to walk whilst secondary outcome
      measures included dorsiflexor torque and strength, measures of 'activity' and
      'participation' and adverse effects. DATA COLLECTION AND ANALYSIS: Methodological
      quality was evaluated by two authors using the van Tulder criteria. Three studies
      with altogether 139 participants were included in the review. Heterogeneity of
      the studies precluded pooling the data. MAIN RESULTS: Early surgery did not
      significantly affect walking speed in a trial including 20 children with Duchenne
      muscular dystrophy. After one year, the mean difference (MD) of the 28 feet
      walking time was 0.00 seconds (95% confidence interval (CI) -0.83 to 0.83) and
      the MD of the 150 feet walking time was -2.88 seconds, (95% CI -8.18 to 2.42). In
      a trial with altogether 26 participants with Charcot-Marie-Tooth disease
      (hereditary motor and sensory neuropathy), long-term strength training
      significantly increased walking speed on a 6 metre timed walk (MD -0.70 seconds,
      95% CI -1.17 to -0.23) but not on a 50 metre timed walk (MD -1.9 seconds, 95% CI 
      4.09 to 0.29). In a trial of a 24-week strength training programme in 28
      participants with myotonic dystrophy, there was no significant change in walking
      speed on either a 6 or 50 metre walk. AUTHORS' CONCLUSIONS: Using the primary
      outcome of ability to walk, only one study demonstrated a positive effect and
      that was an exercise programme for people with Charcot-Marie-Tooth disease.
      Surgery was not significantly effective in children with Duchenne Muscular
      Dystrophy. More evidence generated by methodologically sound trials is required.

PMID- 17443533
TI  - Adjuvant radiotherapy for stage I endometrial cancer.
AB  - BACKGROUND: The role of adjuvant radiotherapy (both pelvic external beam
      radiotherapy and vaginal intracavity brachytherapy) in stage I endometrial cancer
      following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH
      and BSO) remains unclear. OBJECTIVES: To assess the efficacy of adjuvant
      radiotherapy following surgery for stage I endometrial cancer. SEARCH STRATEGY:
      The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE,
      CancerLit, Physician Data Query (PDQ) of National Cancer Institute. Handsearching
      was also carried out where appropriate. SELECTION CRITERIA: Randomised controlled
      trials (RCTs) which compared adjuvant radiotherapy versus no radiotherapy
      following surgery for patients with stage I endometrial cancer were included.
      DATA COLLECTION AND ANALYSIS: Quality of the studies was assessed and data
      collected using a predefined data collection form. The primary endpoint was
      overall survival. Secondary endpoints were locoregional recurrence, distant
      recurrence and endometrial cancer death. Data on quality of life (QOL) and
      morbidity were also collected. A meta-analysis on included trials was performed
      using the Cochrane Collaboration Review Manager Software 4.2. MAIN RESULTS: The
      meta-analysis was performed on four trials (1770 patients). The addition of
      pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a
      relative risk (RR) of 0.28 (95% confidence interval (CI) 0.17 to 0.44, p <
      0.00001), which is a 72% reduction in the risk of pelvic relapse (95% CI 56% to
      83%) and an absolute risk reduction of 6% (95% CI of 4 to 8%). The number needed
      to treat (NNT) to prevent one locoregional recurrence is 16.7 patients (95% CI
      12.5 to 25). The reduction in the risk of locoregional recurrence did not
      translate into either a reduction in the risk of distant recurrence or death from
      all causes or endometrial cancer death. A subgroup analysis of women with
      multiple high risk factors (including stage 1c and grade 3) showed a trend toward
      the reduction in the risk of death from all causes and endometrial cancer death
      in patients who underwent adjuvant external beam radiotherapy. AUTHORS'
      CONCLUSIONS: Patients with stage I endometrial carcinoma have different risks of
      local and distant recurrence depending on the presence of risk factors including
      stage 1c, grade 3, lymphovascular space invasion and age. Though external beam
      pelvic radiotherapy reduced locoregional recurrence by 72%, there is no evidence
      to suggest that it reduced the risk of death. In patients with multiple high risk
      factors, including stage 1c and grade 3, there was a trend towards a survival
      benefit and adjuvant external beam radiotherapy may be justified. For patients
      with only one risk factor, grade 3 or stage 1c, no definite conclusion can be
      made and data from ongoing studies ( ASTEC; Lukka) are awaited. External beam
      radiotherapy carries a risk of toxicity and should be avoided in stage 1
      endometrial cancer patients with no high risk factors.

PMID- 17443534
TI  - Topical agents and dressings for fungating wounds.
AB  - BACKGROUND: Fungating wounds arise from primary, secondary or recurrent malignant
      disease and are associated with advanced cancer. A small proportion of patients
      may achieve healing following surgical excision but treatment is usually
      palliative. Fungating wound management usually aims to slow disease progression
      and optimise quality of life by alleviating physical symptoms, such as copious
      exudate, malodour, pain and the risk of haemorrhage, through appropriate dressing
      and topical agent selection. OBJECTIVES: To conduct a systematic review of the
      evidence of the effects of dressings and topical agents on quality of life and
      symptoms that impact on quality of life in people with fungating malignant
      wounds. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) and the Wounds Group Specialised Register in August 2006. The
      Cochrane Breast Cancer Group and the Pain and Palliative Care Group were
      contacted for relevant studies. The Allied and Complementary Medicine (AMED)
      database was searched in January 2007. There was no restriction on language or
      date of publication. SELECTION CRITERIA: Randomised controlled trials (RCTs) or,
      in their absence, controlled clinical trials (CCTs) with a concurrent control
      group, both published and unpublished, and written in any language, were eligible
      for inclusion. DATA COLLECTION AND ANALYSIS: Data extraction was undertaken by
      one author and checked for accuracy by a second author. Two review authors
      independently assessed trial quality. MAIN RESULTS: Two trials involving 63
      people were included. One RCT in women with superficial breast lesions compared
      6% miltefosine solution with placebo and found that miltefosine delayed tumour
      progression. However, this trial had methodological limitations. A second trial
      compared topical metronidazole with placebo and found that metronidazole reduced
      malodour. However, this trial also had methodological limitations and was
      underpowered. AUTHORS' CONCLUSIONS: There is weak evidence from one small trial
      that 6% miltefosine solution applied topically to people with superficial
      fungating breast lesions (smaller than 1cm) who have received either previous
      radiotherapy, surgery, hormonal therapy or chemotherapy for their breast cancer
      may slow disease progression. There is insufficient evidence in this review to
      give a clear direction for practice with regard to improving quality of life or
      managing wound symptoms associated with fungating wounds. More research is
      needed.

PMID- 17443535
TI  - Vasectomy occlusion techniques for male sterilization.
AB  - BACKGROUND: Vasectomy is an increasingly popular and effective family planning
      method. A variety of vasectomy techniques are used worldwide, including various
      vas occlusion techniques (excision and ligation, thermal or electrocautery, and
      mechanical and chemical occlusion methods), as well as vasectomy with vas
      irrigation or with fascial interposition. Vasectomy guidelines largely rely on
      information from observational studies. Ideally, the choice of vasectomy
      techniques should be based on the best available evidence from randomized
      controlled trials. OBJECTIVES: The objective of this review was to compare the
      effectiveness, safety, acceptability and costs of vasectomy techniques for male
      sterilization. SEARCH STRATEGY: We searched the computerized databases of
      CENTRAL, MEDLINE, EMBASE, POPLINE and LILACS. In addition, we searched the
      reference lists of relevant articles and book chapters. SELECTION CRITERIA: We
      included randomized controlled trials comparing vasectomy techniques. DATA
      COLLECTION AND ANALYSIS: We assessed all titles and abstracts located in the
      literature searches. Two reviewers independently extracted data from articles
      identified for inclusion. Outcome measures include contraceptive efficacy,
      safety, discontinuation, and acceptability. MAIN RESULTS: Six studies met the
      inclusion criteria. One trial compared vas occlusion with clips versus a
      conventional vasectomy technique. No difference was found in failure to reach
      azoospermia. Three trials examined vasectomy with vas irrigation. Two studies
      looked at irrigation with water versus no irrigation, while one examined
      irrigation with water versus the spermicide euflavine. None found a difference
      between the groups for time to azoospermia. However, one trial reported that the
      median number of ejaculations to azoospermia was lower in the euflavine group
      compared to the water irrigation group. One high-quality trial compared vasectomy
      with fascial interposition versus vasectomy without fascial interposition. The
      fascial interposition group was less likely to have vasectomy failure. Fascial
      interposition had more surgical difficulties, but the groups were similar in side
      effects. Lastly, one trial found that an intra-vas was less likely to produce
      azoospermia than was no-scalpel vasectomy. More men were satisfied with the intra
      vas device, however. AUTHORS' CONCLUSIONS: For vas occlusion with clips or
      vasectomy with vas irrigation, no conclusions can be made as those studies were
      of low quality and underpowered. Fascial interposition reduced vasectomy failure.
      An intra-vas device was less effective in reducing sperm count than was no
      scalpel vasectomy. Randomized controlled trials examining other vasectomy
      techniques were not available. More and better quality research is needed to
      examine vasectomy techniques.

PMID- 17443536
TI  - Strategies for the removal of short-term indwelling urethral catheters in adults.
AB  - BACKGROUND: Approximately 15% to 25% of all hospitalised patients have indwelling
      urethral catheters, mainly to assist clinicians to accurately monitor urine
      output during acute illness or following surgery, to treat urinary retention, and
      for investigative purposes. OBJECTIVES: The objective of this review was to
      determine the best strategies for the removal of catheters from patients with a
      short-term indwelling urethral catheter. The main outcome of interest was the
      number of patients who required recatheterisation following removal of indwelling
      urethral catheter. SEARCH STRATEGY: We searched the Cochrane Incontinence Group
      Specialised Register (searched 7 December 2005), the Cochrane Central Register of
      Controlled Trials (The Cochrane Library 2006, Issue 2), MEDLINE (January 1966 to
      12 July 2006), EMBASE (January 1980 to 12 July 2006), CINAHL (January 1982 to 12
      July 2006), Nursing Collection (January 1995 to January 2002) and reference lists
      of relevant articles and conference proceedings were searched. We also contacted
      manufacturers and researchers in the field. No language or other restrictions
      were applied. SELECTION CRITERIA: All randomised and quasi-randomised controlled
      trials (RCTs) that compared the effects of alternative strategies for removal of
      short-term indwelling urethral catheters on patient outcomes were considered for
      inclusion in the review. DATA COLLECTION AND ANALYSIS: Eligibility of the trials
      for inclusion in the review, details of eligible trials and the methodological
      quality of the trials were assessed independently by two reviewers. Relative
      risks (RR) for dichotomous data and a weighted mean difference (WMD) for
      continuous data were calculated with 95% confidence intervals (CI). Where
      synthesis was inappropriate, trials were considered separately. MAIN RESULTS:
      Twenty six trials involving a total of 2933 participants were included in the
      review. One trial included three treatment groups. In 11 RCTs amongst 1389
      people, there was no significant difference in need for recatheterisation,
      although recatheterisation after removal at night was more likely to be during
      working hours. Pooled results demonstrated that, following urological surgery and
      procedures, patients whose indwelling urethral catheters were removed at midnight
      passed significantly larger volumes at their first void (Difference (fixed) 96
      ml; 95% CI 62 to 130). Similar findings were reported for patients following TURP
      (Difference (fixed) 27; 95% CI 23 to 31). Removal at midnight was also associated
      with longer time to first void, and shorter lengths of hospitalisation (relative
      risk of not going home on day of removal = 0.71, 95% CI 0.64 to 0.79). Results in
      13 trials amongst 1422 participants having early rather than delayed catheter
      removal were consistent with a higher risk of voiding problems and a lower risk
      of infection, with shorter hospitalisation. In three trials involving 234
      participants the data were too few to assess differential effects of catheter
      clamping compared with free drainage prior to withdrawal. No eligible trials
      compared flexible with fixed duration of catheterisation, or assessed
      prophylactic alpha sympathetic blocker drugs prior to catheter removal. AUTHORS'
      CONCLUSIONS: There is suggestive but inconclusive evidence of a benefit from
      midnight removal of the indwelling urethral catheter. There are resource
      implications but the magnitude of these is not clear from the trials. The
      evidence also suggests shorter hospital stay after early rather than delayed
      catheter removal but the effects on other outcomes are unclear. There is little
      evidence on which to judge other aspects of management, such as catheter
      clamping.

PMID- 17443537
TI  - Prolotherapy injections for chronic low-back pain.
AB  - BACKGROUND: Prolotherapy involves repeated injections of irritant solutions to
      strengthen lumbosacral ligaments and reduce some types of chronic low-back pain;
      spinal manipulation and exercises are often used to enhance its effectiveness.
      OBJECTIVES: To determine the efficacy of prolotherapy in adults with chronic low
      back pain. SEARCH STRATEGY: We searched CENTRAL 2006, Issue 3 and MEDLINE,
      EMBASE, CINAHL, and AMED from their respective beginnings to October 2006, with
      no restrictions on language, and consulted content experts. SELECTION CRITERIA:
      We included randomised (RCT) and quasi-randomised controlled trials (QRCT) that
      compared prolotherapy injections to control injections, alone or in combination
      with other treatments, which measured pain or disability before and after the
      intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently
      selected the trials and assessed methodological quality. Intervention protocols
      varied from study to study, making meta-analysis impossible. MAIN RESULTS: We
      identified five high quality studies with a total of 366 participants. All
      measured pain or disability levels at six months, and four measured the
      proportion of participants reporting a greater than 50% reduction in pain or
      disability scores. Three randomized controlled trials (206 participants) found
      that prolotherapy injections alone are no more effective than control injection
      for chronic low-back pain and disability. At six months, there was no difference
      between groups in mean pain or disability scores (2 RCTs; 184 participants) and
      no difference in proportions who reported over 50% improvement in pain or
      disability (3 RCTs; 206 participants). These trials could not be pooled due to
      clinical heterogeneity. Two RCTs (160 participants) found that prolotherapy
      injections, given with spinal manipulation, exercise, and other therapies, are
      more effective than control injections for chronic low-back pain and disability.
      At six months, one study reported a significant difference between groups in mean
      pain and disability scores, whereas the other study did not. Both studies
      reported a significant difference in the proportion of individuals who reported
      over 50% reduction in disability or pain. Co-interventions confounded
      interpretation of results and clinical heterogeneity in the trials prevented
      pooling. AUTHORS' CONCLUSIONS: There is conflicting evidence regarding the
      efficacy of prolotherapy injections for patients with chronic low-back pain. When
      used alone, prolotherapy is not an effective treatment for chronic low-back pain.
      When combined with spinal manipulation, exercise, and other co-interventions,
      prolotherapy may improve chronic low-back pain and disability. Conclusions are
      confounded by clinical heterogeneity amongst studies and by the presence of co
      interventions.

PMID- 17443538
TI  - Fetal pulse oximetry for fetal assessment in labour.
AB  - BACKGROUND: Pulse oximetry could contribute to the evaluation of fetal well-being
      during labour. OBJECTIVES: To compare the effectiveness and safety of fetal pulse
      oximetry with conventional surveillance techniques. SEARCH STRATEGY: We searched
      the Cochrane Pregnancy and Childbirth Group's Trials Register (November 2006),
      MEDLINE (1994 to November 2006), EMBASE (1994 to November 2006) and Current
      Contents (1994 to November 2006). SELECTION CRITERIA: All published and
      unpublished randomised controlled trials that compared maternal and fetal
      outcomes when fetal pulse oximetry was used in labour, with or without concurrent
      use of conventional fetal surveillance, compared with using cardiotocography
      (CTG) alone. DATA COLLECTION AND ANALYSIS: At least two independent authors
      performed data extraction. Analyses were performed on an intention-to-treat
      basis. We sought additional information from the investigators of three of the
      reported trials. MAIN RESULTS: Five published trials comparing fetal pulse
      oximetry and CTG with CTG alone (or when fetal pulse oximetry values were
      blinded) were included. The published trials, with some unpublished data,
      reported on a total of 7424 pregnancies. Differing entry criteria necessitated
      separate analyses, rather than meta-analysis of all trials. Four trials reported
      no significant differences in the overall caesarean section rate between those
      monitored with fetal oximetry and those not monitored with fetal pulse oximetry
      or for whom the fetal pulse oximetry results were masked. Neonatal seizures and
      hypoxic ischemic encephalopathy were rare. No studies reported details of
      assessment of long-term disability. There was a statistically significant
      decrease in caesarean section for nonreassuring fetal status in the fetal pulse
      oximetry plus CTG group compared to the CTG group in two analyses: (i) gestation
      from 36 weeks with fetal blood sample (fetal blood sampling) not required prior
      to study entry (relative risk (RR) 0.68, 95% confidence interval (CI) 0.47 to
      0.99); and (ii) when fetal blood sampling was required prior to study entry (RR
      0.03, 95% CI 0.00 to 0.44). There was no statistically significant difference in
      caesarean section for dystocia when fetal pulse oximetry (fetal pulse oximetry)
      was added to CTG monitoring, compared with CTG monitoring alone, although the
      incidence rates varied between the trials. AUTHORS' CONCLUSIONS: The data provide
      limited support for the use of fetal pulse oximetry when used in the presence of
      a nonreassuring CTG, to reduce caesarean section for nonreassuring fetal status.
      The addition of fetal pulse oximetry does not reduce overall caesarean section
      rates. A better method to evaluate fetal well-being in labour is required.

PMID- 17443539
TI  - Routine hospital admission versus out-patient or home care in children at
      diagnosis of type 1 diabetes mellitus.
AB  - BACKGROUND: In many places, children newly diagnosed with type 1 diabetes
      mellitus are admitted to hospital for metabolic stabilisation and training, even
      if they are not acutely ill. Out-patient or home based management of these
      children could avoid the stress associated with a hospital stay, could provide a
      more natural learning environment for the child and its family, and might reduce
      costs for both the health care system and the families. OBJECTIVES: To assess the
      effects of routine hospital admission compared to out-patient or home-based
      management in children newly diagnosed with type 1 diabetes mellitus. SEARCH
      STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, and the
      British Nursing Index. Additionally, we searched reference lists of relevant
      studies identified and contacted one of the trialists about further studies.
      SELECTION CRITERIA: Comparative studies of initial hospitalisation compared to
      home-based and/or out-patient management in children with newly diagnosed type 1
      diabetes. DATA COLLECTION AND ANALYSIS: Studies were independently selected by
      two reviewers. Data extraction and quality assessment of trials were done
      independently by two reviewers. Authors of included studies were contacted for
      missing information. Results were summarised descriptively, using tables and
      text. MAIN RESULTS: Seven studies were included in the review, including a total
      of 298 children in the out-patient/home group. The one high quality trial
      identified suggested that home-based management of children with newly diagnosed
      type 1 diabetes may lead to slightly improved long term metabolic control (at two
      and three years follow-up). No differences between comparison groups were found
      in any of the psychosocial and behavioural variables assessed or in rates of
      acute diabetic complications within two years. Parental costs were found to be
      decreased, while health system costs were increased, leaving total social costs
      virtually unchanged. None of the other studies assessing metabolic control found
      a difference between the comparison groups. There seemed to be no differences in
      hospitalisations or acute diabetic complications between the out-patient/home
      groups and the hospital groups. AUTHORS' CONCLUSIONS: Due to the generally low
      quality or limited applicability of the studies identified, the results of this
      review are inconclusive. On the whole, the data seem to suggest that where
      adequate out-patient/home management of type 1 diabetes in children at diagnosis
      can be provided, this does not lead to any disadvantages in terms of metabolic
      control, acute diabetic complications and hospitalisations, psychosocial
      variables and behaviour, or total costs.

PMID- 17443540
TI  - Scalpel versus no-scalpel incision for vasectomy.
AB  - BACKGROUND: Currently, the two most common surgical techniques for approaching
      the vas during vasectomy are the incisional method and the no-scalpel technique.
      Whereas the conventional incisional technique involves the use of a scalpel to
      make one or two incisions, the no-scalpel technique uses a sharp-pointed, forceps
      like instrument to puncture the skin. The no-scalpel technique aims to reduce
      adverse events, especially bleeding, bruising, hematoma, infection and pain and
      to shorten the operating time. OBJECTIVES: The objective of this review was to
      compare the effectiveness, safety, and acceptability of the incisional versus no
      scalpel approach to the vas. SEARCH STRATEGY: We searched the computerized
      databases of CENTRAL, MEDLINE, EMBASE, POPLINE and LILACS in May 2006. In
      addition, we searched the reference lists of relevant articles and book chapters.
      SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials
      were included in this review. No language restrictions were placed on the
      reporting of the trials. DATA COLLECTION AND ANALYSIS: We assessed all titles and
      abstracts located in the literature searches and two authors independently
      extracted data from the articles identified for inclusion. Outcome measures
      included safety, acceptability, operating time, contraceptive efficacy, and
      discontinuation. MAIN RESULTS: Two randomized controlled trials evaluated the no
      scalpel technique and differed in their findings. The larger trial demonstrated
      less perioperative bleeding (Odds ratio (OR) 0.49; 95% Confidence Interval (CI)
      0.27 to 0.89) and pain during surgery (OR 0.75; 95% CI 0.61 to 0.93), scrotal
      pain (OR 0.63; 95% 0.50 to 0.80), and incisional infection (OR 0.21; 95% CI 0.06
      to 0.78) during follow up than the standard incisional group. Both studies found
      less hematoma with the no-scalpel technique (OR 0.23; 95% CI 0.15 to 0.36).
      Operations using the no-scalpel approach were faster and had a quicker resumption
      of sexual activity. The smaller study did not find these differences; however,
      the study could have failed to detect differences due to a small sample size as
      well as a high loss to follow up. Neither trial found differences in vasectomy
      effectiveness between the two approaches to the vas. AUTHORS' CONCLUSIONS: The no
      scalpel approach to the vas resulted in less bleeding, hematoma, infection, and
      pain as well as a shorter operation time than the traditional incision technique.
      No difference in effectiveness was found between the two approaches.

PMID- 17443541
TI  - Effectiveness of brief alcohol interventions in primary care populations.
AB  - BACKGROUND: Many trials reported that brief interventions are effective in
      reducing excessive drinking. However, some trials have been criticised for being
      clinically unrepresentative and unable to inform clinical practice. OBJECTIVES:
      To assess the effectiveness of brief intervention, delivered in general practice
      or based primary care, to reduce alcohol consumption SEARCH STRATEGY: We searched
      the Cochrane Drug and Alcohol Group specialised register (February 2006), MEDLINE
      (1966 to February 2006), EMBASE (1980 to February 2006), CINAHL (1982 to February
      2006), PsycINFO (1840 to February 2006), Science Citation Index (1970 to February
      2006), Social Science Citation Index (1970 to February 2006), Alcohol and Alcohol
      Problems Science Database (1972 to 2003), reference lists of articles. SELECTION
      CRITERIA: Randomised controlled trials, patients presenting to primary care not
      specifically for alcohol treatment; brief intervention of up to four sessions.
      DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data and
      assessed trial quality. Random effects meta-analyses, sub-group, sensitivity
      analyses, and meta-regression were conducted. MAIN RESULTS: The meta-analysis
      included 21 RCTs (7,286 participants), showing that participants receiving brief
      intervention reduced their alcohol consumption compared to the control group
      (mean difference: -41 grams/week, 95% CI: -57 to -25), although there was
      substantial heterogeneity between trials (I2 = 52%). Sub-group analysis (8
      studies, 2307 participants) confirmed the benefit of brief intervention in men
      (mean difference: -57 grams/week, 95% CI: -89 to -25, I2 = 56%), but not in women
      (mean difference: -10 grams/week, 95% CI: -48 to 29, I2 = 45%). Meta-regression
      showed a non-significant trend of an increased reduction in alcohol consumption
      of 1.1, 95%CI: -0.05 to 2.2 grams/week, p=0.06, for each extra minute of
      treatment exposure, but no relationship between the reduction in alcohol
      consumption and the efficacy score of the trial. Extended intervention when
      compared with brief intervention was associated with a non-significantly greater
      reduction in alcohol consumption (mean difference = -28, 95%CI: -62 to 6
      grams/week, I2 = 0%) AUTHORS' CONCLUSIONS: Brief interventions consistently
      produced reductions in alcohol consumption. When data were available by gender,
      the effect was clear in men at one year of follow up, but unproven in women.
      Longer duration of counselling probably has little additional effect. The lack of
      differences in outcomes between efficacy and effectiveness trials suggests that
      the current literature had clear relevance to routine primary care. Future trials
      should focus on women and on delineating the most effective components of
      interventions.

PMID- 17443542
TI  - Constraint-induced movement therapy in the treatment of the upper limb in
      children with hemiplegic cerebral palsy.
AB  - BACKGROUND: Children with hemiplegic cerebral palsy learn strategies to manage
      daily tasks (for example play) using one hand and often the affected limb is
      disregarded or not used. Constraint-induced movement therapy (CIMT) is emerging
      as a treatment approach for use with children with hemiplegic cerebral palsy. It
      aims to increase spontaneous use of the affected upper limb and thereby limit the
      effects of developmental disregard. CIMT is based on two fundamental principles:
      constraint of the non-affected limb and massed practice of therapeutic tasks with
      the affected limb. OBJECTIVES: The objective of this review was to evaluate the
      effectiveness of CIMT, modified CIMT or Forced Use in the treatment of the
      affected upper limb in children with hemiplegic cerebral palsy. SEARCH STRATEGY:
      We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2006, Issue 3), MEDLINE (1966 to August Week 4 2006), CINAHL
      (1982 to July Week 3 2006), EMBASE (1980 to August 2006), PsychInfo (1985 to
      August Week 4 2006) and reference lists of all relevant articles. SELECTION
      CRITERIA: All randomised controlled trials (RCTs) and controlled clinical trials
      (CCTs) comparing CIMT, modified CIMT and Forced Use with traditional services
      such as occupational therapy, physiotherapy or no treatment were selected. DATA
      COLLECTION AND ANALYSIS: Two review authors extracted the data independently
      using standardised forms. Each trial was assessed for internal validity with
      differences in ratings resolved by discussion. Data were extracted and entered
      into Review Manager 4.2 where appropriate. MAIN RESULTS: Three studies met the
      inclusion criteria. The results of one RCT showed a trend for positive treatment
      effect favouring CIMT using the Dissociated Movement subscale of the Quality of
      Upper Extremity Skills Test (QUEST). Other outcome measures, that were without
      reported psychometric properties, showed significant treatment effects. A CCT
      demonstrated a significant treatment effect favouring modified CIMT at two and
      six months using the Assisting Hand Assessment (AHA). Another trial with
      inaccurate reporting and ambiguous methodology, showed a significant treatment
      effect at 6 weeks on the self care component of the WeeFIM using a Forced Use
      protocol. All other measures showed no significant treatment effect. AUTHORS'
      CONCLUSIONS: This systematic review found a significant treatment effect using
      modified CIMT in a single trial. A positive trend favouring CIMT and Forced Use
      was also demonstrated. Given the limited evidence, the use of CIMT, modified CIMT
      and Forced Use should be considered experimental in children with hemiplegic
      cerebral palsy. Further research using adequately powered RCTs, rigorous
      methodology and valid and reliable outcome measures is essential to provide
      higher level support of the effectiveness of CIMT for children with hemiplegic
      cerebral palsy.

PMID- 17443543
TI  - Double wall versus single wall incubator for reducing heat loss in very low birth
      weight infants in incubators.
AB  - BACKGROUND: Studies have shown improved survival of newborn infants maintained in
      the thermoneutral range. The concept of an incubator with additional insulation,
      a double plexiglass wall, is appealing for very low birth weight infants as it
      may help to provide a thermoneutral environment. OBJECTIVES: To assess the
      effects of double walled incubator versus a single wall incubator on insensible
      water loss, rate of oxygen consumption, episodes of hypothermia, time to regain
      birth weight, duration of hospitalization and infant mortality in premature
      infants. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal
      Review Group was used. This included searches of electronic databases: Oxford
      Database of Perinatal Trials, Cochrane Central Register of Controlled Trials
      (CENTRAL, The Cochrane Library, Issue 1, 2006), MEDLINE (1966 - 2006), EMBASE,
      previous reviews including cross references, abstracts, conference and symposia
      proceedings, expert informants in all published languages, and CINAHL (1982 -
      2006). SELECTION CRITERIA: Only studies using random or quasi-random methods of
      allocation were considered for this review. Eligible studies assessed at least
      one of the outcome variables identified as important to this topic. DATA
      COLLECTION AND ANALYSIS: Independent data extraction and quality assessment of
      included trials was conducted by the review authors. Data were analyzed using
      generic inverse variance methodology and weighted mean difference (WMD). Results
      are presented with 95% confidence intervals. Meta-analysis was undertaken using a
      fixed effect model. MAIN RESULTS: Three studies met the criteria. Four other
      studies were excluded, as they did not compare double versus single wall
      incubators (details of the studies are given in the included and excluded studies
      section). Double wall incubators have the advantage of decreasing heat loss,
      decreasing heat production and decreasing radiant heat loss when compared to
      single wall incubators. There is also the advantage of reduced oxygen
      consumption. A minimal increase in conductive heat loss was noted when compared
      to single wall incubators. All of these effects are small and do not support the
      proposition that double wall incubators have a beneficial effect on long term
      outcomes including mortality or the duration of hospitalization. AUTHORS'
      CONCLUSIONS: Although it appears that caring for extremely small infants in
      double wall incubators may theoretically result in shorter hospitalization and
      may have metabolic advantages, this review was unable to find any data in the
      literature to support or refute this hypothesis. The studies do not provide any
      evidence that the small decrease in heat loss improves clinical outcome.
      Therefore, the available data is insufficient to directly guide clinical
      practice.

PMID- 17443544
TI  - Dan Shen agents for acute ischaemic stroke.
AB  - BACKGROUND: Based mainly on experimental data that indicates improvement to the
      cerebral microcirculation, Dan Shen, a herbal medicine, is widely used in the
      treatment of acute ischaemic stroke in China. OBJECTIVES: To assess the effects
      of Dan Shen agents in patients with acute ischaemic stroke. SEARCH STRATEGY: We
      searched the Cochrane Stroke Group Trials Register (last searched July 2006), the
      register of the Cochrane Complementary Field (last searched July 2006) and the
      Chinese Stroke Trials Register (last searched August 2006). In addition, we
      searched the following bibliographic databases: the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2006), MEDLINE (1996
      to August 2006), EMBASE (1980 to August 2006), CINAHL (1982 to August 2006), AMED
      (1985 to August 2006), and the China Biological Medicine Database (CBM-disc)
      (1979 to August 2006). We handsearched 10 Chinese journals, searched clinical
      trials and research databases, scanned reference lists and contacted the
      pharmaceutical company manufacturing Dan Shen. We also attempted to contact trial
      authors to obtain further data. SELECTION CRITERIA: Randomised or quasi
      randomised controlled trials comparing Dan Shen agents with placebo or open
      control in patients with acute ischaemic stroke. DATA COLLECTION AND ANALYSIS:
      Two review authors independently selected trials for inclusion, assessed trial
      quality, and extracted the data. MAIN RESULTS: Six trials involving 494 patients
      were included. Three trials are awaiting assessment. Numbers of deaths and
      dependent patients at the end of follow up of at least three months were not
      reported in the six included trials. Only two trials reported adverse events. All
      trials measured the outcome 'significant improvement in neurological deficit at
      the end of treatment'. Dan Shen agents were associated with a significant
      increase in the number of patients with the outcome (Peto odds ratio 3.02, 95%
      confidence interval 1.73 to 5.26). No deaths were reported within the first two
      weeks of treatment or during the whole follow-up period. The trials did not
      include any assessment of quality of life. AUTHORS' CONCLUSIONS: The
      methodological quality of all included studies was poor, and reliable conclusions
      could not be drawn from the present data. Further high-quality randomised
      controlled trials should be performed.

PMID- 17443545
TI  - Steroid hormones for contraception in men.
AB  - BACKGROUND: Male hormonal contraception has been an elusive goal. Administration
      of sex steroids to men can shut off sperm production through effects on the
      pituitary and hypothalamus. However, this approach also decreases production of
      testosterone, so 'add-back' therapy is needed. OBJECTIVES: To summarize all
      randomized controlled trials of male hormonal contraception. SEARCH STRATEGY: We
      searched the computerized databases CENTRAL, MEDLINE, EMBASE, POPLINE, and LILACS
      (each from inception to March 2006) for randomized controlled trials of hormonal
      contraception in men. We wrote to authors of identified trials to seek
      unpublished or published trials that we might have missed. SELECTION CRITERIA: We
      included all randomized controlled trials in any language that compared a steroid
      hormone with another contraceptive. We excluded non-steroidal male
      contraceptives, such as gossypol. We included both placebo and active-regimen
      control groups. All trials identified included only healthy men with normal semen
      analyses. DATA COLLECTION AND ANALYSIS: Azoospermia (absence of spermatozoa on
      semen examination) was the primary outcome measure. Data were insufficient to
      examine pregnancy rates and side effects. MAIN RESULTS: We found 30 trials that
      met our inclusion criteria. The proportion of men who achieved azoospermia varied
      widely in reports to date. A few important differences emerged from these trials:
      levonorgestrel implants combined with injectable testosterone enanthate (TE) were
      more effective than levonorgestrel 125 microg daily combined with testosterone
      patches; levonorgestrel 500 mug daily improved the effectiveness of TE 100 mg
      injected weekly; desogestrel 150 mug was less effective than desogestrel 300 mug
      (with testosterone pellets); testosterone undecanoate (TU) 500 mg was less likely
      to produce azoospermia than TU 1000 mg (with levonorgestrel implants);
      norethisterone enanthate 200 mg with TU 1000 mg led to more azoospermia when
      given every 8 weeks versus 12 weeks; four implants of 7-alpha-methyl-19
      nortestosterone (MENT) were more effective than two MENT implants. Several trials
      showed promising efficacy in terms of percentages with azoospermia. Three
      examined desogestrel and testosterone preparations or etonogestrel (metabolite of
      desogestrel) and testosterone, and two examined levonorgestrel and testosterone.
      AUTHORS' CONCLUSIONS: No male hormonal contraceptive is ready for clinical use.
      Most trials were small exploratory studies. As a result, their power to detect
      important differences was limited and their results imprecise. In addition, the
      definition of oligozoospermia has been imprecise or inconsistent. To avoid bias,
      future trials need more attention to the methodological requirements for
      randomized controlled trials. More trials with adequate power would also be
      helpful.

PMID- 17443546
TI  - Granulocyte-colony stimulating factor (G-CSF) as an adjunct to antibiotics in the
      treatment of pneumonia in adults.
AB  - BACKGROUND: Granulocyte colony stimulating factor (G-CSF) is a naturally
      occurring cytokine that has been shown to increase neutrophil function and
      number. Exogenous administration of recombinant G-CSF (filgrastim, pegfilgrastim
      or lenograstim) has found extensive use in the treatment of febrile neutropenia,
      but its role in the treatment of infection in non-neutropenic hosts is less well
      defined. OBJECTIVES: We explored the role of G-CSF as an adjunct to antibiotics
      in the treatment of pneumonia in non-neutropenic adults. SEARCH STRATEGY: For
      this updated review we searched the Cochrane Central Register of Controlled
      Trials (CENTRAL) (The Cochrane Library, Issue 4, 2006); MEDLINE (1950 to January
      2007); EMBASE (1988 to January 2007); and online databases of clinical trials
      (www.controlled-trials.com, updated 10 November, 2006). SELECTION CRITERIA: We
      considered randomized controlled trials (RCTs) which included hospitalized adult
      patients with either community-acquired pneumonia or hospital-acquired pneumonia.
      DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and
      assessed trial quality. The primary outcome measure was 28-day mortality.
      Secondary outcome measures included other markers of mortality as well as markers
      of adverse events, including organ dysfunction. An assessment of methodological
      quality was made for each study. MAIN RESULTS: Six studies with a total of 2018
      people were identified. G-CSF use appeared to be safe with no increase in the
      incidence of total serious adverse events (pooled odds ratio (OR) 0.91; 95%
      confidence interval (CI): 0.73 to 1.14) or organ dysfunction. However, the use of
      G-CSF was not associated with improved 28-day mortality (pooled OR 0.81; 95% CI:
      0.52 to 1.27). AUTHORS' CONCLUSIONS: There is no current evidence supporting the
      routine use of G-CSF in the treatment of pneumonia. Studies in which G-CSF is
      administered prophylactically or earlier in therapy may be of interest.

PMID- 17443547
TI  - Pulp management for caries in adults: maintaining pulp vitality.
AB  - BACKGROUND: There is a range of treatment options for the management of the pulp
      in extensively decayed teeth. These include direct and indirect pulp capping,
      pulpotomy or pulpectomy. If the tooth is symptomatic or if there are periapical
      bone changes, then endodontic treatment is required. However, if the tooth is
      asymptomatic but the caries is extensive, there is no consensus as to the best
      method of management. In addition, there has been a recent move towards using
      alternative materials and methods such as the direct or indirect placement of
      bonding agents and mineral trioxide aggregate. Most studies have investigated the
      management of asymptomatic carious teeth with or without an exposed dental pulp
      using various capping materials (e.g. calcium hydroxide, Ledermix, Triodent,
      Biorex, etc.). However, there is no long term data regarding the outcome of
      management of asymptomatic, carious teeth according to different regimens.
      OBJECTIVES: This study aims to assess the effectiveness of techniques used to
      treat asymptomatic carious teeth and maintain pulp vitality. SEARCH STRATEGY:
      Electronic searches of the following databases were undertaken: The Cochrane Oral
      Health Group's Trials Register (March 2006), the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library 2006, Issue 1), MEDLINE (1966
      to week 4, February 2006), EMBASE (1974 to 13 March 2006), National Research
      Register (March 2006), Science Citation Index - SCISEARCH (1981 to March 2006).
      Detailed search strategies were developed for each database. Handsearching and
      screening of reference lists were undertaken. There was no restriction with
      regard to language of publication. SELECTION CRITERIA: Studies included were
      randomised controlled trials (RCTs). Asymptomatic vital permanent teeth with
      extensive caries were included. Studies were those which compared techniques to
      maintain pulp vitality. Outcome measures included clinical success and adverse
      events. DATA COLLECTION AND ANALYSIS: Data were independently extracted by three
      review authors. Authors were contacted for details of randomisation and
      withdrawals and a quality assessment was carried out. The Cochrane Oral Health
      Group's statistical guidelines were followed. MAIN RESULTS: Only four RCTs were
      identified. Interventions examined included: Ledermix, glycerrhetinic
      acid/antibiotic mix, zinc oxide eugenol, calcium hydroxide, Cavitec, Life, Dycal,
      potassium nitrate, dimethyl isosorbide, and polycarboxylate cement. Only one
      study showed a statistically significant finding; potassium nitrate/dimethyl
      isosorbide/polycarboxylate cement resulted in fewer clinical symptoms than
      potassium nitrate/polycarboxylate cement or polycarboxylate cement alone when
      used as a capping material for carious pulps. AUTHORS' CONCLUSIONS: It was
      disappointing that there were so few studies which could be considered as being
      suitable for inclusion in this review. The findings from this review do not
      suggest that there should be any significant change from accepted conventional
      practice procedures when the pulp of the carious tooth is considered. Further
      well designed RCTs are needed to investigate the potential of contemporary
      materials which may be suitable when used in the management of carious teeth. It
      is recognised that it is difficult to establish the 'ideal' clinical study when
      ethical approval for new materials must be sought and strict attention to case
      selection, study protocol and interpretation of data is considered. It is also
      not easy to recruit sufficient numbers of patients meeting the necessary
      criteria.

PMID- 17443548
TI  - Adhesives for fixed orthodontic bands.
AB  - BACKGROUND: Orthodontic treatment involves using fixed or removable appliances
      (dental braces) to correct the positions of teeth. It has been shown that the
      quality of treatment result obtained with fixed appliances is much better than
      with removable appliances. Fixed appliances are, therefore, favoured by most
      orthodontists for treatment. The success of a fixed orthodontic appliance depends
      on the metal attachments (brackets and bands) being attached securely to the
      teeth so that they do not become loose during treatment. Brackets are usually
      attached to the front and side teeth, whereas bands (metal rings that go round
      the teeth) are more commonly used on the back teeth (molars). A number of
      adhesives are available to attach bands to teeth and it is important to
      understand which group of adhesives bond most reliably, as well as reducing or
      preventing dental decay during the treatment period. OBJECTIVES: To evaluate the
      effectiveness of the adhesives used to attach bands to teeth during fixed
      appliance treatment, in terms of:(1) how often the bands come off during
      treatment; and(2) whether they protect the banded teeth against decay during
      fixed appliance treatment. SEARCH STRATEGY: Electronic databases were searched:
      the Cochrane Oral Health Group's Trials Register (29th January 2007), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library
      2007, Issue 1), MEDLINE (1966 to 29th January 2007) and EMBASE (1980 to 29th
      January 2007). A search of the internet was also undertaken. There was no
      restriction with regard to publication status or language of publication.
      SELECTION CRITERIA: Randomised and controlled clinical trials (RCTs and CCTs)
      (including split-mouth studies) of adhesives used to attach orthodontic bands to
      molar teeth were selected. Patients with full arch fixed orthodontic appliance(s)
      who had bands attached to molars were included. DATA COLLECTION AND ANALYSIS: All
      review authors were involved in study selection, validity assessment and data
      extraction without blinding to the authors, adhesives used or results obtained.
      All disagreements were resolved by discussion. MAIN RESULTS: Five RCTs and three
      CCTs were identified as meeting the review's inclusion criteria. All the included
      trials were of split-mouth design. Four trials compared chemically cured zinc
      phosphate and chemically cured glass ionomer; three trials compared chemically
      cured glass ionomer cement with light cured compomer; one trial compared
      chemically cured glass ionomer with a chemically cured glass phosphonate. Data
      analysis was often inappropriate within the studies meeting the inclusion
      criteria. AUTHORS' CONCLUSIONS: There is insufficient high quality evidence with
      regard to the most effective adhesive for attaching orthodontic bands to molar
      teeth. Further RCTs are required.

PMID- 17443549
TI  - Medicinal herbs for esophageal cancer.
AB  - BACKGROUND: Esophageal cancer is the seventh leading cause of cancer death
      worldwide. Traditional Chinese medicinal herbs are sometimes used as an adjunct
      to radiotherapy or chemotherapy for this type of cancer. OBJECTIVES: To assess
      the efficacy and possible adverse effects of the addition of Chinese medicinal
      herbs to treatment with radiotherapy or chemotherapy for esophageal cancer.
      SEARCH STRATEGY: We searched the Cochrane Upper Gastrointestinal and Pancreatic
      Diseases Group Trials Register, The Cochrane Library, MEDLINE, EMBASE, AMED
      (Allied and Complementary Medicine Database), CBM (Chinese Biomedical Database),
      China National Knowledge Infrastructure, the Chinese Cochrane Centre Controlled
      Trials Register and CISCOM (The Research Council for Complementary Medicine) (up
      to June 2004). Databases of ongoing trials, the internet and reference lists were
      also searched. SELECTION CRITERIA: Randomised controlled trials comparing the use
      of radiotherapy or chemotherapy with and without the addition of Chinese
      medicinal herbs. DATA COLLECTION AND ANALYSIS: At least two review authors
      extracted data and assessed trial quality. MAIN RESULTS: Two studies were
      included. The numbers of participants in these two trials were 42 and 80, 122 in
      total. Both studies were analysed separately because of the differences in
      interventions used. Although one study reported a positive result, the majority
      of outcome measurements from the two studies showed no significant benefit with
      the addition of Chinese herbal medicines to radiotherapy or chemotherapy. There
      was statistically significant improvement in quality of life with the additional
      Huachansu injection, however, no statistically significant improvement was found
      in short-term therapy effects, one-year survival rate or the adverse effect of
      radiation-induced esophagitis. AUTHORS' CONCLUSIONS: The included studies were of
      low quality. The results suggest Zhenxiang capsules or Huachansu injection may
      not improve short-term therapy effects or one-year survival rate when used as
      adjunct treatment to chemo- or radiotherapy in the treatment of esophageal
      cancer. The quality of life may be improved by Huachansu injection. The results
      suggest that more high-quality trials on Huachansu injection and other Chinese
      herbal medicines are needed in the future.

PMID- 17443550
TI  - EMG biofeedback for the recovery of motor function after stroke.
AB  - BACKGROUND: Electromyographic biofeedback (EMG-BFB) is a technique that is
      believed to have additional benefit when used with standard physiotherapy for the
      recovery of motor function in stroke patients. However, evidence from individual
      trials and previous systematic reviews has been inconclusive. OBJECTIVES: To
      assess the effects of EMG-BFB for motor function recovery following stroke.
      SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last
      searched 30 March 2006), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 4, 2005), MEDLINE (1966 to November 2005),
      EMBASE (1980 to November 2005), CINAHL (1983 to November 2005), PsycINFO (1974 to
      November 2005) and First Search (1966 to November 2005). We scanned reference
      lists for relevant articles and contacted equipment manufacturers and
      distributors. SELECTION CRITERIA: Randomised and quasi-randomised studies
      comparing EMG-BFB with control for motor function recovery in stroke patients.
      DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial
      quality and extracted data. Where possible we contacted study authors for further
      information. Any reported adverse effects were noted. MAIN RESULTS: Thirteen
      trials involving 269 people were included. All trials compared EMG-BFB plus
      standard physiotherapy to standard physiotherapy either alone or with sham EMG
      BFB. Only one study used a motor strength assessment scale for evaluation of
      patients, which indicated benefit from EMG-BFB (WMD 1.09, 95% CI 0.48 to 1.70).
      EMG-BFB did not have a significant benefit in improving range of motion (ROM)
      through the ankle (SMD 0.05, 95% CI -0.36 to 0.46), knee or wrist joints.
      However, one trial suggested a benefit in ROM at the shoulder (SMD 0.88, 95% CI
      0.07 to 1.70). Change in stride length or gait speed was not improved by EMG-BFB.
      Two studies used different assessment scores to quantify gait quality. One of
      these suggested a beneficial effect of EMG-BFB (SMD 0.90, 95% CI 0.01 to 1.78).
      Most of the studies examining functional outcomes used different assessment
      scales, which made meta-analysis impossible. Two studies that used the same scale
      did show a beneficial effect (SMD 0.69, 95% CI 0.15 to 1.23). AUTHORS'
      CONCLUSIONS: Despite evidence from a small number of individual studies to
      suggest that EMG-BFB plus standard physiotherapy produces improvements in motor
      power, functional recovery and gait quality when compared to standard
      physiotherapy alone, combination of all the identified studies did not find a
      treatment benefit. Overall the results are limited because the trials were small,
      generally poorly designed and utilised varying outcome measures.

PMID- 17443551
TI  - Meglitinide analogues for type 2 diabetes mellitus.
AB  - BACKGROUND: In type 2 diabetes mellitus, impairment of insulin secretion is an
      important component of the disease. Meglitinide analogues are a class of oral
      hypoglycaemic agents that increase insulin secretion, in particular, during the
      early phase of insulin release. OBJECTIVES: The aim of this review was to assess
      the effects of meglitinide analogues in patients with type 2 diabetes mellitus.
      SEARCH STRATEGY: We searched several databases including The Cochrane Library,
      MEDLINE and EMBASE. We also contacted manufacturers and searched ongoing trials
      databases, and the American Diabetes Association (ADA) and European Association
      for the Study of Diabetes (EASD) websites. SELECTION CRITERIA: We included
      randomised controlled, parallel or cross-over trials comparing at least 10 weeks
      of treatment with meglitinide analogues to placebo, head-to-head, metformin or in
      combination with insulin. DATA COLLECTION AND ANALYSIS: Two authors independently
      extracted data and assessed trial quality. MAIN RESULTS: Fifteen trials involving
      3781 participants were included. No studies reported the effect of meglitinides
      on mortality or morbidity. In the eleven studies comparing meglitinides to
      placebo, both repaglinide and nateglinide resulted in a reductions in
      glycosylated haemoglobin (0.1% to 2.1% reduction in HbA1c for repaglinide; 0.2%
      to 0.6% for nateglinide). Only two trials compared repaglinide to nateglinide
      (342 participants), with greater reduction in glycosylated haemoglobin in those
      receiving repaglinide. Repaglinide (248 participants in three trials) had a
      similar degree of effect in reducing glycosylated haemoglobin as metformin.
      Nateglinide had a similar or slightly less marked effect on glycosylated
      haemoglobin than metformin (one study, 355 participants). Weight gain was
      generally greater in those treated with meglitinides compared with metformin (up
      to three kg in three months). Diarrhoea occurred less frequently and
      hypoglycaemia occurred more frequently but rarely severely enough as to require
      assistance. AUTHORS' CONCLUSIONS: Meglitinides may offer an alternative oral
      hypoglycaemic agent of similar potency to metformin, and may be indicated where
      side effects of metformin are intolerable or where metformin is contraindicated.
      However, there is no evidence available to indicate what effect meglitinides will
      have on important long-term outcomes, particularly mortality.

PMID- 17443552
TI  - Antiplatelet agents for preventing pre-eclampsia and its complications.
AB  - BACKGROUND: Pre-eclampsia is associated with deficient intravascular production
      of prostacyclin, a vasodilator, and excessive production of thromboxane, a
      vasoconstrictor and stimulant of platelet aggregation. These observations led to
      the hypotheses that antiplatelet agents, low-dose aspirin in particular, might
      prevent or delay development of pre-eclampsia. OBJECTIVES: To assess the
      effectiveness and safety of antiplatelet agents for women at risk of developing
      pre-eclampsia. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (July 2006), the Cochrane Central Register of Controlled
      Trials (The Cochrane Library 2005, Issue 1), EMBASE (1994 to November 2005) and
      handsearched congress proceedings of the International and European Societies for
      the Study of Hypertension in Pregnancy. SELECTION CRITERIA: All randomised trials
      comparing antiplatelet agents with either placebo or no antiplatelet agent were
      included. Quasi-random studies were excluded. Participants were pregnant women at
      risk of developing pre-eclampsia. Interventions were any comparisons of an
      antiplatelet agent (such as low-dose aspirin or dipyridamole) with either placebo
      or no antiplatelet. DATA COLLECTION AND ANALYSIS: Two authors assessed trials for
      inclusion and extracted data independently. MAIN RESULTS: Fifty-nine trials
      (37,560 women) are included. There is a 17% reduction in the risk of pre
      eclampsia associated with the use of antiplatelet agents ((46 trials, 32,891
      women, relative risk (RR) 0.83, 95% confidence interval (CI) 0.77 to 0.89),
      number needed to treat (NNT) 72 (52, 119)). Although there is no statistical
      difference in RR based on maternal risk, there is a significant increase in the
      absolute risk reduction of pre-eclampsia for high risk (risk difference (RD) 
      5.2% (-7.5, -2.9), NNT 19 (13, 34)) compared with moderate risk women (RD -0.84 (
      1.37, -0.3), NNT 119 (73, 333)). Antiplatelets were associated with an 8%
      reduction in the relative risk of preterm birth (29 trials, 31,151 women, RR
      0.92, 95% CI 0.88 to 0.97); NNT 72 (52, 119)), a 14% reduction in fetal or
      neonatal deaths (40 trials, 33,098 women, RR 0.86, 95% CI 0.76 to 0.98); NNT 243
      (131, 1,666) and a 10% reduction in small-for-gestational age babies (36 trials,
      23,638 women, RR 0.90, 95% CI0.83 to 0.98). There were no statistically
      significant differences between treatment and control groups for any other
      outcomes. AUTHORS' CONCLUSIONS: Antiplatelet agents, largely low-dose aspirin,
      have moderate benefits when used for prevention of pre-eclampsia and its
      consequences. Further information is required to assess which women are most
      likely to benefit, when treatment is best started, and at what dose.

PMID- 17443553
TI  - Self-management education for adults with epilepsy.
AB  - BACKGROUND: Self-management education has been shown to improve the quality of
      life of people with chronic illnesses. It has been suggested that self-management
      education may improve seizure control and other outcomes in people with epilepsy.
      OBJECTIVES: To review systematically the research literature on the effectiveness
      of self-management education in improving health outcomes for adults with
      epilepsy. SEARCH STRATEGY: We searched MEDLINE (Ovid) (1966 to April 2005),
      EMBASE (Ovid) (1980 to April 2005), CINAHL (Dialog) (1980 to April 2005),
      PsycINFO (Dialog) (1887 to April 2005), and the Cochrane Epilepsy Group's
      Specialised Register (April 2005). We also handsearched Epilepsia and conference
      abstracts and proceedings. Experts in the field were contacted to identify any
      additional trials. We did not impose any language restriction. We re-ran the
      searches in February 2007 and added the identified references to the 'Studies
      awaiting assessment' table. SELECTION CRITERIA: Randomised trials of self
      management education programmes for adults with epilepsy. DATA COLLECTION AND
      ANALYSIS: At least two review authors independently assessed the quality of each
      study and extracted data. MAIN RESULTS: Two trials evaluated the effect of self
      management education for adults with epilepsy, neither of which assessed as being
      of high quality. In total, 483 adults with epilepsy were randomised. Both trials
      showed improvements in seizure frequency and other outcomes, such as knowledge.
      However, we were not able to estimate a summary effect for seizure frequency due
      to a lack of data. AUTHORS' CONCLUSIONS: Self-management education programmes,
      based on increasing understanding through psychosocial methods, may improve
      knowledge about epilepsy, certain behavioural outcomes, and reduce seizure
      frequency. It is, however, not clear how effective self-management programmes of
      epilepsy would be in a more general population of adults with epilepsy, as both
      trials had higher proportions of people with partial seizures than would be
      expected in a community sample.

PMID- 17443554
TI  - Self-management education for children with epilepsy.
AB  - BACKGROUND: Self-management education has been shown to improve the quality of
      life of children and young people with chronic illnesses. It has been suggested
      that self-management education may improve seizure control and other outcomes in
      children and young people with epilepsy. OBJECTIVES: To review systematically the
      research literature on the effectiveness of self-management education in
      improving health outcomes for children and young people with epilepsy. SEARCH
      STRATEGY: We searched the Cochrane Epilepsy Group's Specialised Register (April
      2007), MEDLINE (Ovid) (1966 to February 2007), EMBASE (Ovid) (1980 to February
      2007), CINAHL (Dialog) (1980 to February 2007), and PsycINFO (Dialog) (1887 to
      February 2007). We also handsearched Epilepsia and conference abstracts and
      proceedings. Experts in the field were contacted to identify any additional
      trials. No language restriction was imposed. SELECTION CRITERIA: Randomised
      trials of self-management education programmes for children or young people with
      epilepsy. DATA COLLECTION AND ANALYSIS: At least two review authors independently
      assessed the quality of each study and extracted data. MAIN RESULTS: Only one
      trial involving 167 children was identified that evaluated the effect of a child
      centred model of training for the self-management of two chronic illnesses,
      asthma and epilepsy. The trial was not assessed as being of high quality and the
      methods used to analyse and report the data did not enable us to precisely
      determine the effect of the intervention. However, improvements were seen in
      seizure frequency and other outcomes, such as knowledge and behaviour. AUTHORS'
      CONCLUSIONS: Self-management education programmes that deliver a child-centred
      model of training, may improve knowledge about epilepsy, certain behavioural
      outcomes, and reduce seizure frequency in children and young people with
      epilepsy. However, based on the evidence reviewed, we are not able to determine
      how effective it is, or what the key components of the programme should be.

PMID- 17443555
TI  - Antibiotics for acute laryngitis in adults.
AB  - BACKGROUND: Acute laryngitis is a common illness worldwide. Diagnosis is often
      made by case history alone and treatment is often directed towards controlling
      symptoms. OBJECTIVES: The aim of this review was to assess the effectiveness of
      different antibiotic therapies in adults suffering acute laryngitis. A secondary
      objective was to report the rates of adverse events associated with these
      treatments. SEARCH STRATEGY: We systematically screened the following electronic
      databases: the Cochrane Central Register of Controlled Trials (The Cochrane
      Library Issue 4, 2006); MEDLINE (January 1966 to December Week 2 2006); and
      EMBASE (1974 to June 2006), LILACS (from 1982 to December 2006 ) and BIOSIS (1980
      to June 2002). Other strategies included hand searching relevant journals,
      searching ongoing trial databases and general databases such as Google scholar.
      SELECTION CRITERIA: Randomized controlled trials comparing any antibiotic therapy
      with placebo in acute laryngitis. The main outcome measurement was objective
      voice scores. DATA COLLECTION AND ANALYSIS: Data were independently extracted by
      two review authors and then descriptively synthesized. MAIN RESULTS: Only two
      trials met study inclusion criteria after extensive literature searches. One
      hundred participants were randomly selected to receive either penicillin V (800
      mg twice a day for five days), or an identical placebo, in a study of penicillin
      V in acute laryngitis in adults. A tape recording of each patient reading a
      standardized text was obtained during the first visit, subsequently during re
      examination after one and two weeks, and at follow up after two to six months. No
      significant differences were found between the groups. The trial also measured
      symptoms reported by participants and found no significant differences. The
      second trial investigated erythromycin for treating acute laryngitis in 106
      adults. The mean objective voice scores measured at the first visit, at re
      examination after one and two weeks, and at follow up after two to six months did
      not significantly differ between control and intervention groups. At one week
      there were significant beneficial differences in the severity of reported vocal
      symptoms as judged by the participants (P = 0.042). Comparing the erythromycin
      and placebo groups on subjective voice scores the a priori relative risk (RR) was
      0.7 (95% confidence interval (CI) 0.51 to 0.96, P = 0.034) and the number needed
      to treat (NNT) was 4.5. AUTHORS' CONCLUSIONS: Antibiotics appear to have no
      benefit in treating acute laryngitis. Erythromycin could reduce voice disturbance
      at one week and cough at two weeks when measured subjectively. We consider that
      these outcomes are not relevant in clinical practice. The implications for
      practice are that prescribing antibiotics should not be done in the first
      instance as they will not objectively improve symptoms.

PMID- 17443556
TI  - Contracts between patients and healthcare practitioners for improving patients'
      adherence to treatment, prevention and health promotion activities.
AB  - BACKGROUND: Contracts are a verbal or written agreement that a patient makes with
      themselves, with healthcare practitioners, or with carers, where participants
      commit to a set of behaviours related to the care of a patient. Contracts aim to
      improve the patients' adherence to treatment or health promotion programmes.
      OBJECTIVES: To assess the effects of contracts between patients and healthcare
      practitioners on patients' adherence to treatment, prevention and health
      promotion activities, the stated health or behaviour aims in the contract,
      patient satisfaction or other relevant outcomes, including health practitioner
      behaviour and views, health status, reported harms, costs, or denial of treatment
      as a result of the contract. SEARCH STRATEGY: We searched: the Cochrane Consumers
      and Communication Review Group's Specialised Register (in May 2004); the Cochrane
      Central Register of Controlled Trials (CENTRAL), (The Cochrane Library 2004,
      issue 1); MEDLINE 1966 to May 2004); EMBASE (1980 to May 2004); PsycINFO (1966 to
      May 2004); CINAHL (1982 to May 2004); Dissertation Abstracts. A: Humanities and
      Social Sciences (1966 to May 2004); Sociological Abstracts (1963 to May 2004); UK
      National Research Register (2000 to May 2004); and C2-SPECTR, Campbell
      Collaboration (1950 to May 2004). SELECTION CRITERIA: We included randomised
      controlled trials comparing the effects of contracts between healthcare
      practitioners and patients or their carers on patient adherence, applied to
      diagnostic procedures, therapeutic regimens or any health promotion or illness
      prevention initiative for patients. Contracts had to specify at least one
      activity to be observed and a commitment of adherence to it. We included trials
      comparing contracts with routine care or any other intervention. DATA COLLECTION
      AND ANALYSIS: Selection and quality assessment of trials were conducted
      independently by two review authors; single data extraction was checked by a
      statistician. We present the data as a narrative summary, given the wide range of
      interventions, participants, settings and outcomes, grouped by the health problem
      being addressed. MAIN RESULTS: We included thirty trials, all conducted in high
      income countries, involving 4691 participants. Median sample size per group was
      21. We examined the quality of each trial against eight standard criteria, and
      all trials were inadequate in relation to three or more of these standards.
      Trials evaluated contracts in addiction (10 trials), hypertension (4 trials),
      weight control (3 trials) and a variety of other areas (13 trials). Sixteen
      trials reported at least one outcome that showed statistically significant
      differences favouring the contracts group, five trials reported at least one
      outcome that showed differences favouring the control group and 26 trials
      reported at least one outcome without differences between groups. Effects on
      adherence were not detected when measured over longer periods. AUTHORS'
      CONCLUSIONS: There is limited evidence that contracts can potentially contribute
      to improving adherence, but there is insufficient evidence from large, good
      quality studies to routinely recommend contracts for improving adherence to
      treatment or preventive health regimens.

PMID- 17443557
TI  - Probiotics for the prevention of pediatric antibiotic-associated diarrhea.
AB  - BACKGROUND: Antibiotics alter the microbial balance within the gastrointestinal
      tract. Probiotics may prevent antibiotic-associated diarrhea (AAD) via
      restoration of the gut microflora. Antibiotics are prescribed frequently in
      children and AAD is common in this population. OBJECTIVES: To assess the efficacy
      and adverse effects of probiotics (any specified strain or dose) for the
      prevention of antibiotic-associated diarrhea in children. To assess adverse
      events associated with the use of probiotics when co-administered with
      antibiotics in children. SEARCH STRATEGY: MEDLINE, EMBASE, CENTRAL, CINAHL ,
      AMED, and the Web of Science (inception to August 2006) were searched along with
      specialized registers including the Cochrane IBD/FBD Review Group, CISCOM,
      Chalmers PedCAM Research Register and trial registries from inception to 2005.
      Letters were sent to authors of included trials, nutra/pharmaceutical companies,
      and experts in the field requesting additional information on ongoing or
      unpublished trials. Conference proceedings, dissertation abstracts, and reference
      lists from included and relevant articles were hand searched. SELECTION CRITERIA:
      Randomized, parallel, controlled (placebo, active, or no treatment) trials
      comparing co-administered probiotics with antibiotics for the prevention of
      diarrhea secondary to antibiotic use in children (0 to 18 years). DATA COLLECTION
      AND ANALYSIS: Methodological quality assessment and data extraction were
      conducted independently by two authors (BCJ, AS). Dichotomous data (incidence of
      diarrhea, adverse events) were combined using pooled relative risks, and
      continuous data (mean duration of diarrhea, mean daily stool frequency) as
      weighted mean differences, along with their corresponding 95% confidence
      intervals. Adverse events were summarized using risk difference. For overall
      pooled results on the incidence of diarrhea, a priori sensitivity analyses
      included per protocol versus intention to treat, random versus fixed effects, and
      methodological quality criterion. Subgroup analysis were conducted on probiotic
      strain, dose, definition of antibiotic-associated diarrhea, and antibiotic agent.
      MAIN RESULTS: Ten studies met the inclusion criteria. Trials included treatment
      with either Lactobacilli spp., Bifidobacterium spp., Streptococcus spp., or
      Saccharomyces boulardii alone or in combination. Six studies used a single strain
      probiotic agent and four combined two probiotic strains. The per protocol
      analysis for 9/10 trials reporting on the incidence of diarrhea show
      statistically significant results favouring probiotics over active/non active
      controls (RR 0.49; 95% CI 0.32 to 0.74). However, intention to treat analysis
      showed non-significant results overall (RR 0.90; 95% CI 0.50 to 1.63). Five of
      ten trials monitored for adverse events (n = 647); none reported a serious
      adverse event. AUTHORS' CONCLUSIONS: Probiotics show promise for the prevention
      of pediatric AAD. While per protocol analysis yields treatment effect estimates
      that are both statistically and clinically significant, as does analysis of high
      quality studies, the estimate from the intention to treat analysis was not
      statistically significant. Future studies should involve probiotic strains and
      doses with the most promising evidence (e.g., Lactobacillus GG, Lactobacillus
      sporogenes, Saccharomyces boulardii at 5 to 40 billion colony forming units/day).
      Research done to date does not permit determination of the effect of age (e.g.,
      infant versus older children) or antibiotic duration (e.g., 5 days versus 10
      days). Future trials would benefit from a validated primary outcome measure for
      antibiotic-associated diarrhea that is sensitive to change and reflects what
      treatment effect clinicians, parents, and children consider important. The
      current data are promising, but it is premature to routinely recommend probiotics
      for the prevention of pediatric AAD.

PMID- 17443558
TI  - Dipyrone for acute primary headaches.
AB  - BACKGROUND: Dipyrone is used to treat headaches in many countries, but is not
      available in others (particularly the USA and UK) because of its association with
      potentially life-threatening blood dyscrasias such as agranulocytosis.
      OBJECTIVES: To determine the effectiveness and safety of dipyrone for acute
      primary headaches in adults and children. SEARCH STRATEGY: We searched the
      Cochrane Pain, Palliative & Supportive Care Group's Trials Register; the Cochrane
      Central Register of Controlled Trials; MEDLINE; EMBASE; LILACS, and the reference
      lists of included studies. SELECTION CRITERIA: Double-blind randomised controlled
      trials of dipyrone for the symptomatic relief of acute primary headaches in
      adults and children. DATA COLLECTION AND ANALYSIS: Three authors independently
      screened articles, extracted data, assessed trial quality and analysed results.
      Relative risks (RRs), risk differences (RDs), weighted mean differences (WMDs),
      and numbers-needed-to-treat (NNTs) were calculated as appropriate. MAIN RESULTS:
      Four trials involving a total of 636 adult subjects were included. Methodological
      quality was generally high. One study each evaluated oral and intravenous
      dipyrone for episodic tension-type headache (ETTH); two trials evaluated
      intravenous dipyrone for migraine, but only one of these described pain outcomes.
      No pediatric trials were identified. The largest trial (n = 356) evaluated two
      doses (0.5 g, 1 g) of oral dipyrone for ETTH, which were significantly better
      than placebo for pain relief. The 1 g dose was also significantly better than
      acetylsalicylic acid (ASA) 1 g . A smaller trial (n = 60) evaluated intravenous
      dipyrone 1 g versus placebo for ETTH. RRs were statistically significant
      favouring dipyrone for pain-free and headache improvement outcomes. Finally, one
      trial (n = 134) evaluated intravenous dipyrone 1 g versus placebo for pain
      outcomes in patients with migraine. RRs were again statistically significant
      favouring dipyrone for pain-free and headache improvement outcomes. Two of the
      four trials assessed adverse events. No serious adverse events were reported, and
      no significant differences in adverse events were detected between dipyrone and
      comparators (placebo and ASA). AUTHORS' CONCLUSIONS: Evidence from a small number
      of trials suggests that dipyrone is effective for ETTH and migraine. No serious
      adverse events were observed in the included trials, but agranulocytosis is rare
      and would probably not be observed in such a relatively small sample. A study now
      ongoing in Latin America may clarify the true risk of agranulocytosis associated
      with dipyrone use.

PMID- 17443559
TI  - Topical lidocaine for the treatment of postherpetic neuralgia.
AB  - BACKGROUND: The cause of postherpetic neuralgia is damage to peripheral neurons,
      dorsal root ganglia, and the dorsal horn of the spinal cord, secondary to herpes
      zoster infection (shingles). In postherpetic neuralgia, peripheral neurons
      discharge spontaneously and have lowered activation thresholds, and exhibit an
      exaggerated response to stimuli. Topical lidocaine dampens peripheral nociceptor
      sensitisation and central nervous system hyperexcitability, and may benefit
      patients with postherpetic neuralgia. OBJECTIVES: To examine the efficacy and
      safety of topical lidocaine in the treatment of postherpetic neuralgia. SEARCH
      STRATEGY: We searched the Cochrane Pain, Palliative and Supportive Care Group
      Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL),
      MEDLINE, EMBASE, and LILACS, SIGLE for conference proceedings, Citation Index,
      the reference lists of all eligible trials, key textbooks, and previous
      systematic reviews. We also wrote to authors of all identified trials. SELECTION
      CRITERIA: Randomised or quasi-randomised trials comparing all topical
      applications of lidocaine, including gels and patches in patients of all ages
      with postherpetic neuralgia (pain persisting at the site of shingles at least one
      month after the onset of the acute rash). DATA COLLECTION AND ANALYSIS: Two
      review authors extracted data, and a third checked them. We obtained some missing
      data from the US Food and Drugs Administration. MAIN RESULTS: Three trials
      involving 182 topical lidocaine treated participants and 132 control participants
      were included. Two trials gave data on pain relief, and the remaining study
      provided data on secondary outcome measures. The largest trial published as an
      abstract compared topical lidocaine patch to a placebo patch and accounted for
      150 of the 314 patients (48%).A meta-analysis combining two of the three studies
      identified a significant difference between the topical lidocaine and control
      groups for the primary outcome measure: a mean improvement in pain relief
      according to a pain relief scale. Topical lidocaine relieved pain better than
      placebo (P = 0.003). There was a statistical difference between the groups for
      the secondary outcome measure of mean VAS score reduction (P = 0.03), but this
      was only for a single small trial. There were a similar number of adverse skin
      reactions in both treatment and placebo groups. The highest recorded blood
      lidocaine concentration varied between 59 ng/ml and 431 ng/ml between trials. The
      latter figure is high and the authors of the study suggest that the sample had
      been contaminated during the assay procedure. AUTHORS' CONCLUSIONS: There is
      insufficient evidence to recommend topical lidocaine as a first-line agent in the
      treatment of postherpetic neuralgia with allodynia. Further research should be
      undertaken on the efficacy of topical lidocaine for other chronic neuropathic
      pain disorders, and also to compare different classes of drugs (e.g. topical
      anaesthetics versus anti-epileptics).

PMID- 17443560
TI  - Chinese medicinal herbs to treat the side-effects of chemotherapy in breast
      cancer patients.
AB  - BACKGROUND: Short term side-effects of chemotherapy include fatigue, nausea,
      vomiting, mucositis and myelosuppression or neutropenia. These occur during the
      course of treatment and generally resolve within months of completion of
      chemotherapy. A variety of Chinese medicinal herbs have been used for managing
      these side effects. OBJECTIVES: To assess the effectiveness and safety of Chinese
      medicinal herbs in alleviating chemotherapy-induced short term side effects in
      breast cancer patients. SEARCH STRATEGY: We searched The Cochrane Breast Cancer
      Specialised Register (15/02/2007), The Cochrane Central Register of Controlled
      Trials (CENTRAL); (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to December
      2006); EMBASE (1990 to December 2006); and Chinese Biomedical Literature (2006,
      Issue 4). A number of journals were hand searched. SELECTION CRITERIA: Randomised
      controlled trials comparing chemotherapy with or without Chinese herbs in women
      with breast cancer. DATA COLLECTION AND ANALYSIS: Two authors independently
      extracted the data, which were analysed using RevMan 4.2. For dichotomous data,
      we estimated the relative risk. For continuous data, we calculated the weighted
      mean difference. MAIN RESULTS: We identified seven randomised controlled trials
      involving 542 breast cancer patients undergoing or having recently undergone
      chemotherapy. All studies were conducted and published in China. We did not pool
      the results because few studies were identified and no more than two used the
      same intervention. All were of low quality and used CMH plus chemotherapy
      compared with chemotherapy alone.CMH combined with chemotherapy showed no
      statistically significant difference for the outcomes of phlebitis and alopecia.
      Only one study showed an improvement in nausea and vomiting, and in fatigue.
      Three indicated an improvement in white blood cells in the group receiving CMH.
      Two showed an increase in percentage changes in T-lymphocyte subsets CD4 and CD8.
      One study showed a statistically significant difference for CMH in percentage
      changes in T-lymphocyte subsets CD3, CD4 and CD8. Two herbal compounds may have
      improved quality of life. One study reported that CMH may have some effect on
      reducing toxicity in liver and kidney, but differences were not statistically
      significant. AUTHORS' CONCLUSIONS: This review provides limited evidence about
      the effectiveness and safety of Chinese medicinal herbs in alleviating
      chemotherapy induced short term side effects. Chinese medicinal herbs, when used
      together with chemotherapy, may offer some benefit to breast cancer patients in
      terms of bone marrow improvement and quality of life, but the evidence is too
      limited to make any confident conclusions. Well designed clinical trials are
      required before any conclusions can be drawn about the effectiveness and safety
      of CHM in the management of breast cancer patients.

PMID- 17443561
TI  - Treatment for superficial thrombophlebitis of the leg.
AB  - BACKGROUND: The optimal treatment of superficial thrombophlebitis (ST) of the
      legs remains poorly defined. While improving or relieving the local painful
      symptoms, treatment should aim at preventing venous thromboembolism (VTE), which
      might complicate the natural history of ST. OBJECTIVES: To assess the efficacy
      and safety of topical, medical, and surgical treatments in patients presenting
      with ST of the legs. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases
      Group searched their specialized register (last searched 16 February 2007), and
      the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched Issue
      1, 2007. We searched MEDLINE (1966 to January 2006), EMBASE (1980 to January
      2006), and handsearched reference lists of relevant papers and conference
      proceedings. SELECTION CRITERIA: Randomized trials evaluating topical, medical,
      and surgical treatments for ST of the leg including participants with a clinical
      diagnosis of ST of the legs or objective diagnosis of a thrombus in the
      superficial vein. DATA COLLECTION AND ANALYSIS: Two authors assessed the trials
      for inclusion in the review, extracted the data, and assessed the quality of the
      studies. Data were extracted independently from the included studies and any
      disagreements resolved by consensus. MAIN RESULTS: Twenty-four studies involving
      2469 participants with ST of the legs were included in this review. The
      methodological quality of most of the trials was poor. Treatment ranged from low
      molecular weight heparin (LMWH), to non-steroidal anti-inflammatory agents
      (NSAIDs), topical treatment, surgery, oral, intramuscular, and intravenous
      treatments. Both LMWH and NSAIDs significantly reduced the incidence of ST
      extension or recurrences by about 70% compared with placebo and both seemed to
      have a similar efficacy and safety. Overall, topical treatments improved local
      symptoms. However, no data were provided on the effects of these treatments on
      VTE and ST extension. Surgical treatment combined with elastic stockings in ST
      was associated with a lower VTE rate and ST progression, compared with elastic
      stockings alone. AUTHORS' CONCLUSIONS: Low molecular weight heparin and NSAIDs
      appear as the current best therapeutic options for ST of the legs. While the
      available data are too limited to make clear recommendations, an intermediate
      dose of LMWH for at least a month might be advised. Further research is needed to
      assess the role of NSAIDs and LMWH, the optimal doses and duration of treatment,
      and whether a combination therapy may be more effective than single treatment.
      Adequately designed and conducted studies are required to clarify the role of
      topical and surgical treatments.

PMID- 17443562
TI  - Preoperative bathing or showering with skin antiseptics to prevent surgical site
      infection.
AB  - BACKGROUND: Surgical site infections (SSIs) are wound infections that occur after
      invasive (surgical) procedures. Preoperative bathing or showering with an
      antiseptic skin wash product is a well-accepted procedure for reducing skin
      bacteria (microflora). It is less clear whether reducing skin microflora leads to
      a lower incidence of surgical site infection. OBJECTIVES: To review the evidence
      for preoperative bathing or showering with antiseptics for the prevention of
      hospital-acquired (nosocomial) surgical site infection. SEARCH STRATEGY: We
      searched the Cochrane Wounds Group Specialised Register (December 2005), the
      Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4,
      2005), MEDLINE (January 1966 to December 2005) and reference lists of articles.
      SELECTION CRITERIA: Randomised controlled trials comparing any antiseptic
      preparation used for preoperative full-body bathing or showering with non
      antiseptic preparations in patients undergoing surgery. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed studies for selection, trial quality
      and extracted data. Study authors were contacted for additional information. MAIN
      RESULTS: Six trials involving a total of 10,007 participants were included. Three
      of the included trials had three comparison groups. The antiseptic used in all
      trials was 4% chlorhexidine gluconate (Hibiscrub). Three trials involving 7691
      participants compared chlorhexidine with a placebo. Bathing with chlorhexidine
      compared with a placebo did not result in a statistically significant reduction
      in SSIs; the relative risk of SSI (RR) was 0.91 (95% confidence interval (CI)
      0.80 to 1.04). When only trials of high quality were included in this comparison,
      the RR of SSI was 0.95 (95%CI 0.82 to 1.10). Three trials of 1443 participants
      compared bar soap with chlorhexidine; when combined there was no difference in
      the risk of SSIs (RR 1.02, 95% CI 0.57 to 1.84). Two trials of 1092 patients
      compared bathing with chlorhexidine with no washing, one large study found a
      statistically significant difference in favour of bathing with chlorhexidine (RR
      0.36, 95%CI 0.17 to 0.79). The second smaller study found no difference between
      patients who washed with chlorhexidine and those who did not wash preoperatively.
      AUTHORS' CONCLUSIONS: This review provides no clear evidence of benefit for
      preoperative showering or bathing with chlorhexidine over other wash products, to
      reduce surgical site infection. Efforts to reduce the incidence of nosocomial
      surgical site infection should focus on interventions where effect has been
      demonstrated.

PMID- 17443563
TI  - Acupuncture for vascular dementia.
AB  - BACKGROUND: Dementia is a widespread condition characterized by acquired global
      impairment of intellect, memory and personality, but with no impairment of
      consciousness. There is no definitive medical or surgical treatment for vascular
      dementia. Acupuncture is an ancient Chinese method which has been used for both
      the prevention and treatment of diseases for over three thousand years.
      Preliminary searches revealed more than 105 studies of acupuncture for treating
      vascular dementia. Benefit was reported in up to 70-91% of the treatment group.
      Body acupuncture and electroacupuncture were the most commonly used techniques. A
      comparison of electroacupuncture and acupuncture therapy alone suggested that the
      former was more effective in promoting the recovery of cognitive function.
      OBJECTIVES: The objective is to assess the efficacy and possible adverse effects
      of acupuncture therapy for treating vascular dementia. SEARCH STRATEGY: The
      trials were identified from a search of the Cochrane Dementia and Cognitive
      Improvement group's Specialized Register on 2 February 2007 which contains
      records from all major health care databases and many ongoing trials databases.
      In addition the Allied and Complementary Medicine Database was searched and the
      web was searched using the search engine Copernic. SELECTION CRITERIA: Randomized
      controlled trials testing acupuncture therapy in the treatment of vascular
      dementia were included regardless of language and publication types. The
      intervention and control group had to receive identical treatment apart from the
      acupuncture intervention. In view of possible confounding, studies in which
      acupuncture was combined with other treatments were subjected to subgroup
      analyses. DATA COLLECTION AND ANALYSIS: Titles and abstracts identified from the
      searches were checked by two reviewers. If it was clear that the study did not
      refer to a randomized controlled trial in vascular dementia, it was excluded. If
      it was not clear from the abstract and title, then the full text of study was
      obtained for an independent assessment by two reviewers. The outcomes measured in
      clinical trials of dementia and cognitive impairment often arise from ordinal
      rating scales. Summary statistics were required for each rating scale at each
      assessment time for each treatment group in each trial for change from baseline.
      MAIN RESULTS: In the absence of any suitable randomised placebo-controlled trials
      in this area, we were unable to perform a meta-analysis. AUTHORS' CONCLUSIONS:
      The effectiveness of acupuncture for vascular dementia is uncertain. More
      evidence is required to show that vascular dementia can be treated effectively by
      acupuncture. There are no RCTs and high quality trials are few. Randomised double
      blind placebo controlled trials are urgently needed.

PMID- 17443564
TI  - Preoperative chemotherapy for women with operable breast cancer.
AB  - BACKGROUND: Currently, preoperative chemotherapy is the standard of care in
      locally advanced breast cancer to achieve local tumour downsizing in order to
      make surgery possible. Since the early 1980s, the role of preoperative
      chemotherapy in early stage (or operable) breast cancer has been the subject of
      study. Potential advantages are early introduction of systemic therapy,
      determination of chemosensitivity, reduction of tumour volume and downstaging of
      surgical requirement. Concerns exist about local control after downsized surgery
      and the delay of local treatment in patients with tumours resistant to
      chemotherapy. OBJECTIVES: To assess the effectiveness of preoperative
      chemotherapy in women with operable breast cancer when compared to postoperative
      chemotherapy. SEARCH STRATEGY: The Specialised Register maintained by the
      Editorial Base of the Cochrane Breast Cancer Group was searched on 4th of August
      2005. SELECTION CRITERIA: Randomised trials comparing preoperative chemotherapy
      with postoperative in women with operable breast cancer. DATA COLLECTION AND
      ANALYSIS: Studies were assessed for eligibility and quality, and data were
      extracted by two independent review authors. Hazard ratios were derived for time
      to-event outcomes directly or indirectly using the methods described by Parmar.
      Relative risks were derived for dichotomous outcomes. Meta-analyses were
      performed using fixed effect model. MAIN RESULTS: We identified 14 eligible
      studies which randomised a total of 5,500 women. Median follow-up ranged from 18
      to 124 months. Eight studies described a satisfactory method of
      randomisation.Data, based on 1139 estimated deaths in 4620 women available for
      analysis, show equivalent overall survival rates with a HR of 0.98 (95% CI, 0.87
      to 1.09; p, 0.67; no heterogeneity). Preoperative chemotherapy increases breast
      conservation rates, yet at the associated cost of increased loco regional
      recurrence rates. However, this rate was not increased as long as surgery remains
      part of the treatment even after complete tumour regression (HR, 1.12; 95% CI,
      0.92 to 1.37; p, 0.25; no heterogeneity. Preoperative chemotherapy was associated
      with fewer adverse effects. Pathological complete response is associated with
      better survival than residual disease (HR, 0.48; 95% CI, 0.33 to 0.69; p, < 10
      4). AUTHORS' CONCLUSIONS: This review suggests safe application of preoperative
      chemotherapy in the treatment of women with early stage breast cancer in order to
      down-stage surgical requirement, to evaluate chemosensitivity and to facilitate
      translational research.

PMID- 17443565
TI  - Recombinant factor VIIa for the prevention and treatment of bleeding in patients
      without haemophilia.
AB  - BACKGROUND: Recombinant factor VIIa (rFVIIa) is licensed for use in patients with
      haemophilia and inhibitory allo-antibodies. It is also increasingly being used
      for off-license indications to prevent bleeding in operations where blood loss is
      likely to be high, and/or to stop bleeding that is proving difficult to control
      by other means. OBJECTIVES: To assess the effectiveness of rFVIIa when used
      therapeutically to control active bleeding, or prophylactically to prevent
      (excessive) bleeding in patients without haemophilia. SEARCH STRATEGY: We
      searched the Cochrane Injuries Group's Specialised Register, CENTRAL, MEDLINE,
      EMBASE and other specialised databases up to March 2006. We also searched
      reference lists of articles and contacted experts in the field. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing rFVIIa with placebo, or
      one dose of rFVIIa with another, in any patient population with the exception of
      those with haemophilia. There was no restriction by outcomes examined, but this
      review focuses on mortality, blood loss or control of bleeding, red cell
      transfusion requirements, number of patients transfused and thromboembolic
      adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently assessed
      potentially relevant studies for inclusion. Data were extracted and
      methodological quality was examined. Studies using rFVIIa prophylactically and
      those using rFVIIa therapeutically have been considered separately. Data were
      pooled using fixed and random effects models, but random effects models were
      preferred because of the variability in clinical features of the included
      studies. MAIN RESULTS: Thirteen trials met the inclusion criteria; all were
      placebo-controlled double-blind RCTs. Six trials involving 724 participants
      examined the prophylactic use of rFVIIa; 379 received rFVIIa. There were no
      outcomes by which any observed advantage, or disadvantage, of rFVIIa over placebo
      could not have been observed by chance alone. There were trends in favour of
      rFVIIa for a number of outcomes, particularly the number of participants
      transfused, pooled RR 0.85 (95% CI 0.72 to 1.01) but this was balanced by a trend
      against rFVIIa with respect to thromboembolic adverse events, pooled RR 1.25 (95%
      CI 0.76 to 2.07). Seven trials involving 1214 participants examined the
      therapeutic use of rFVIIa; 687 received rFVIIa. There were no outcomes where any
      observed advantage, or disadvantage, of rFVIIa over placebo could not have been
      observed by chance alone. There was a trend in favour of rFVIIa for reducing
      mortality, RR 0.82 (95% CI 0.64 to 1.04), although no other clear trends in
      favour of rFVIIa were noted for other desired outcomes. Interpretation of these
      results must take into account one study which could not be included in the
      quantitative summary but which showed results strongly in favour of rFVIIa for
      the treatment of intra-cerebral haemorrhage. There was a trend against rFVIIa
      with respect to thromboembolic adverse events; the RR 1.50 (95% CI 0.86 to 2.62).
      AUTHORS' CONCLUSIONS: Although rFVIIa has a role in the management of patients
      with haemophilia, its effectiveness as a more general haemostatic drug, either
      prophylactically or therapeutically, remains uncertain. Its effectiveness as a
      therapeutic agent, particularly for intra-cerebral haemorrhage, looks more
      encouraging than prophylactic use. The use of rFVIIa outside its current licensed
      indications should be very limited and its wider use await the results of ongoing
      and possibly newly commissioned RCTs. In the interim, rFVIIa use should be
      restricted to clinical trials.

PMID- 17443566
TI  - Neoadjuvant chemotherapy versus none for resectable gastric cancer.
AB  - BACKGROUND: Gastric cancer is a major cause of cancer death, and many patients
      are only diagnosed when the cancer has reached an advanced stage. Neoadjuvant
      chemotherapy (NAC), that is, chemotherapy administered shortly before surgical
      treatment, could provide a method of increasing the possibility of complete
      resection and survival. OBJECTIVES: To evaluate the effect of neoadjuvant
      chemotherapy versus none for patients with resectable gastric cancer in terms of
      efficacy and toxicity. SEARCH STRATEGY: Electronic databases including Cochrane
      Library, MEDLINE, EMBASE, CancerLit, Chinese Biomedical Literature Database
      (CBMDISC) and ongoing clinical trials as well as handsearching of conference
      proceedings, were searched to retrieve relevant data. SELECTION CRITERIA:
      Randomized controlled clinical trials of neoadjuvant chemotherapy on resectable
      gastric cancer. DATA COLLECTION AND ANALYSIS: We identified a total of 36
      published citations or meeting abstracts. Thirty-two items were excluded. Of the
      four remaining studies, three stated random allocation but the method of
      randomization was unclear. Two of these employed allocation concealment by sealed
      envelope which was controlled by an independent party. None of the trials was
      double blind. All trials presented a detailed description of the number of
      withdrawals, dropouts and losses to follow-up. MAIN RESULTS: Of the four clinical
      trials enrolled, there were 250 and 332 cases in total, with 106 and 126 deaths
      at the end of follow-up in the NAC and control group, respectively. The OR (odds
      ratio) was 1.05 (95%CI: 0.73-1.50), which was not statistically significant. Of
      the evaluable 129 patients receiving NAC, 28.7% demonstrated either a complete or
      a partial response. Two studies of NAC in resectable gastric cancer had resection
      rate data available for analysis The R0 resection rate in the NAC group was
      comparable to that in the control (OR: 0.96 (95%CI: 0.51-1.83)). The morbidity
      and mortality of NAC varied with the regimens used preoperatively. Of the 129
      patients included in the analyzed studies, some acceptable toxicity was observed.
      AUTHORS' CONCLUSIONS: There is no definite evidence of the effectiveness of NAC
      in resectable gastric cancer, in terms of improvements in patient survival, in
      the trials we reviewed. Neoadjuvant chemotherapy should not be used routinely in
      clinical setting until further results from randomized clinical are available.
      Neoadjuvant chemotherapy of gastric cancer should be applied under the framework
      of clinical trials.

PMID- 17443567
TI  - Wholegrain cereals for coronary heart disease.
AB  - BACKGROUND: There is increasing evidence from observational studies that
      wholegrains can have a beneficial effect on risk factors for coronary heart
      disease (CHD). OBJECTIVES: The primary objective is to review the current
      evidence from randomised controlled trials (RCTs) that assess the relationship
      between the consumption of wholegrain foods and the effects on CHD mortality,
      morbidity and on risk factors for CHD, in participants previously diagnosed with
      CHD or with existing risk factors for CHD. SEARCH STRATEGY: We searched CENTRAL
      (Issue 4, 2005), MEDLINE (1966 to 2005), EMBASE (1980 to 2005), CINAHL (1982 to
      2005), ProQuest Digital Dissertations (2004 to 2005). No language restrictions
      were applied. SELECTION CRITERIA: We selected randomised controlled trials that
      assessed the effects of wholegrain foods or diets containing wholegrains, over a
      minimum of 4 weeks, on CHD and risk factors. Participants included were adults
      with existing CHD or who had at least one risk factor for CHD, such as abnormal
      lipids, raised blood pressure or being overweight. DATA COLLECTION AND ANALYSIS:
      Two of our research team independently assessed trial quality and extracted data.
      Authors of the included studies were contacted for additional information where
      this was appropriate. MAIN RESULTS: Ten trials met the inclusion criteria. None
      of the studies found reported the effect of wholegrain diets on CHD mortality or
      CHD events or morbidity. All 10 included studies reported the effect of
      wholegrain foods or diets on risk factors for CHD. Studies ranged in duration
      from 4 to 8 weeks. In eight of the included studies, the wholegrain component was
      oats. Seven of the eight studies reported lower total and low density
      lipoproteins (LDL) cholesterol with oatmeal foods than control foods. When the
      studies were combined in a meta-analysis lower total cholesterol (-0.20 mmol/L,
      95% confidence interval (CI) -0.31 to -0.10, P = 0.0001 ) and LDL cholesterol
      (0.18 mmol/L, 95% CI -0.28 to -0.09, P < 0.0001) were found with oatmeal foods.
      However, there is a lack of studies on other wholegrains or wholegrain diets.
      AUTHORS' CONCLUSIONS: Despite the consistency of effects seen in trials of
      wholegrain oats, the positive findings should be interpreted cautiously. Many of
      the trials identified were short term, of poor quality and had insufficient
      power. Most of the trials were funded by companies with commercial interests in
      wholegrains. There is a need for well-designed, adequately powered, longer term
      randomised controlled studies in this area. In particular there is a need for
      randomised controlled trials on wholegrain foods and diets other than oats.

PMID- 17443568
TI  - Interventions for pityriasis rosea.
AB  - BACKGROUND: Pityriasis rosea is a scaly rash that mainly affects young adults. It
      can be very itchy but most people recover within 2 to 12 weeks. OBJECTIVES: To
      assess the effects of interventions for pityriasis rosea. SEARCH STRATEGY: We
      searched the Cochrane Skin Group Specialised Register (December 2004), the
      Cochrane Central Register of Controlled Clinical Trials in The Cochrane Library
      (Issue 4, 2004), MEDLINE (1966 to January 2005), EMBASE (1976 to January 2005),
      LILACS (1982 to January 2005), BIOSIS Preview (1980 to June 2002), and ongoing
      trials databases. We scanned bibliographies of published studies, abstracts from
      dermatology conference proceedings, corresponded with trialists and contacted the
      pharmaceutical industry. SELECTION CRITERIA: Randomised controlled trials
      evaluating interventions for pityriasis rosea. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed trial quality and extracted data. We contacted
      study authors to retrieve missing data. MAIN RESULTS: Three trials involving 148
      people were included. One poor quality trial (23 people), compared intravenous
      glycyrrhizin and intravenous procaine. It found no significant difference between
      the two interventions for treating symptoms and rash. One fair quality trial (85
      people), compared the oral antihistamine dexchlorpheniramine (4 mg), the oral
      steroid betamethasone (500 mcg), and a combination of betamethasone (250 mcg) and
      dexchlorpheniramine (2 mg). It found no significant difference in itch resolution
      at two weeks, as rated by the participants, between dexchlorpheniramine and
      betamethasone, and the combination of dexchlorpheniramine and betamethasone.
      However, both dexchlorpheniramine and betamethasone alone seem to be better at
      clearing rash than the combination of dexchlorpheniramine and betamethasone.
      These interventions were not compared with placebo. The small good quality trial
      (40 people) that compared oral erythromycin and placebo found that erythromycin
      was more effective than placebo in terms of rash improvement, as rated by the
      trialists, after two weeks (RR 13.00; 95% CI 1.91 to 88.64). It was also more
      effective in decreasing the itch score (difference of 3.95 points, 95% CI 3.37 to
      4.53). No serious adverse effects were reported for the interventions. Two out of
      17 people on oral erythromycin and 1 out of 17 on placebo reported minor
      gastrointestinal upset. AUTHORS' CONCLUSIONS: We found inadequate evidence for
      efficacy for most treatments for pityriasis rosea. Oral erythromycin may be
      effective in treating the rash and decreasing the itch. However, this result
      should be treated with caution since it comes from only one small RCT. More
      research is necessary to evaluate the efficacy of erythromycin and other
      treatments.

PMID- 17443569
TI  - Recombinant Luteinizing Hormone (rLH) for controlled ovarian hyperstimulation in
      assisted reproductive cycles.
AB  - BACKGROUND: During in vitro fertilization (IVF)/intracytoplasmic sperm injection
      (ICSI) treatment cycles, controlled ovarian hyperstimulation (COH) is performed
      with recombinant follicle stimulating hormone (rFSH) in combination with a
      gonadotrophin-releasing hormone (GnRH) analogue for the prevention of premature
      luteinizing hormone (LH) surges. The use of GnRH analogues however deprives the
      growing follicles of LH. The effectiveness of co-administrating rLH to rFSH for
      COH is at present unclear. OBJECTIVES: To compare the effectiveness and safety of
      a combination of recombinant LH and recombinant FSH with recombinant FSH alone in
      COH protocols in (IVF or ICSI followed by embryo transfer (ET). SEARCH STRATEGY:
      We searched the MDSG Group Specialised Register (searched up to Nov 2006) and
      CENTRAL, MEDLINE and EMBASE (1980 to November 2006) and reference lists of
      articles. SELECTION CRITERIA: Randomised controlled trials comparing COH with
      rFSH alone or in combination with rLH in IVF/ICSI were included. DATA COLLECTION
      AND ANALYSIS: Three review authors independently assessed trial quality and
      extracted data. We sought additional information if necessary. MAIN RESULTS:
      Fourteen trials involving 2612 women were included. Eleven trials involving 2396
      women used a GnRH agonist . There was no evidence of a statistical difference in
      live birth rate reported in two trials (OR 1.51, 95% CI 0.79 to 2.87). There was
      no evidence of a statistical difference in clinical pregnancy rates reported in
      seven trials OR 1.15, 95% CI 0.91 to 1.45. There was no evidence of a statistical
      difference or in ongoing pregnancy rates seven trials OR 1.22, 95% CI 0.95 to
      1.56. Three trials used a GnRH antagonist. No data on live birth rates was
      available. There was no evidence of a statistical difference in clinical
      pregnancy rates (one trial: OR 0.79, 95% CI 0.26 to 2.43) or in ongoing pregnancy
      rates (two trials: OR 0.83, 95% CI 0.39 to 1.80) comparing both groups. The
      pooled pregnancy estimates of trials including only poor responders showed
      significant increase in pregnancy rate, in favour of co-administrating rLH (three
      trials: OR 1.85, 95% CI 1.10 to 3.11) AUTHORS' CONCLUSIONS: There was no evidence
      of a statistical difference in pregnancy outcomes when rLH was used.
      Nevertheless, further large RCTs should be undertaken in long GnRH agonist down
      regulation protocols, since all pooled pregnancy estimates, although not
      statistically different probably due to the small numbers, point towards a
      beneficial effect of co-treatment with rLH, in particular with respect to
      pregnancy-loss and poor-responders.

PMID- 17443570
TI  - Cup feeding versus other forms of supplemental enteral feeding for newborn
      infants unable to fully breastfeed.
AB  - BACKGROUND: Breast milk provides optimal nutrition for newborn infants, and the
      ideal way for infants to receive breast milk is through suckling at the breast.
      Unfortunately, this may not always be possible, as there are numerous reasons why
      a newborn infant may not be able to breastfeed and, as a result, require
      supplemental feeding. Currently, there are a variety of ways in which newborn
      infants can receive supplemental feeds. Traditionally, bottles and nasogastric
      tubes have been used; however, more recently, cup feeding has become a popular
      practice in many nurseries in an attempt to improve breastfeeding rates. There is
      no consistency to guide the choice of supplementation. OBJECTIVES: To determine
      the effects of cup feeding versus other forms of supplemental enteral feeding on
      weight gain and achievement of successful breastfeeding in newborn infants who
      are unable to fully breastfeed. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2006),
      CINAHL (1982 - April 2006) and MEDLINE (1966 - April 2006). SELECTION CRITERIA:
      Randomised or quasi-randomised controlled trials comparing cup feeding to other
      forms of enteral feeding for the supplementation of newborn infants. DATA
      COLLECTION AND ANALYSIS: Quality assessments and data extraction for included
      trials were conducted independently by the review authors. Outcomes reported from
      these studies were: weight gain, proportion not breastfeeding at hospital
      discharge, proportion not feeding at three months of age, proportion not feeding
      at six months of age, proportion not fully feeding at hospital discharge,
      proportion not fully breastfeeding at three months of age, proportion not fully
      breastfeeding at six months of age, average time per feed (minutes), length of
      stay and physiological events of instability such as bradycardia, apnea, and low
      oxygen saturation. For continuous variables such as weight gain, mean differences
      and 95% confidence intervals were reported. For categorical outcomes such as
      mortality, the relative risks (RR) and 95% confidence intervals were reported.
      MAIN RESULTS: Four studies were eligible for inclusion. The experimental
      intervention was cup feeding and the control intervention was bottle feeding in
      all four studies included in this review. There was no statistically significant
      difference in the incidence of not breastfeeding at hospital discharge in three
      included studies (typical RR 0.82, 95% CI 0.62, 1.09) and not breastfeeding at
      three months in two included studies (typical RR 0.88, 95% CI 0.76, 1.03) or six
      months for the one study that reported this outcome (RR 0.91, 95% CI 0.78, 1.05).
      There was a statistically significant difference in not fully breastfeeding at
      hospital discharge (from three included studies) in favour of cup feeding
      (typical RR 0.75, 95% CI 0.61, 0.92). However, this was not statistically
      significant at three months (one study, RR 1.18, 95% CI 0.88, 1.58) or six months
      (one study, RR 1.31, 95% CI 0.89, 1.92). There was no statistically significant
      difference in weight gain from one study that reported this outcome (MD -0.60,
      95% CI -3.21, 2.01). In the one study that assessed it, there was a significantly
      increased length of hospital stay in the cup fed infants [mean difference between
      groups was 10.1 days (95% CI 3.9, 16.3)]. Time to full breastfeeding was not
      assessed in any study. AUTHORS' CONCLUSIONS: Cup feeding cannot be recommended
      over bottle feeding as a supplement to breastfeeding because it confers no
      significant benefit in maintaining breastfeeding beyond hospital discharge and
      carries the unacceptable consequence of a longer stay in hospital.

PMID- 17443571
TI  - Psychological interventions to improve adherence to oral hygiene instructions in
      adults with periodontal diseases.
AB  - BACKGROUND: Adherence to oral hygiene is an important aspect of the treatment of
      periodontal disease. Traditional educational interventions have been shown to be
      of little value in achieving long term behaviour change. OBJECTIVES: The aim of
      this review was to determine the impact of interventions aimed to increase
      adherence to oral hygiene instructions in adult periodontal patients based on
      psychological models and theoretical frameworks. This review considered the
      following outcomes: Observational measures of oral health related behaviour Self
      reported oral health related behaviours, beliefs and attitudes towards oral
      health related behaviour Clinical markers of periodontal disease. SEARCH
      STRATEGY: The Cochrane Oral Health Group's Trials Register (2005), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2004, Issue
      4), MEDLINE (from 1966 to December 2004), EMBASE (from 1980 to December 2004),
      PSYCHINFO (from 1966 to December 2004), Ingenta (from 1998 to December 2004) and
      CINAHL (from 1966 to December 2004). Reference lists from relevant articles were
      searched and the authors of eligible trials were contacted to identify trials and
      obtain additional information. No language restriction was applied. SELECTION
      CRITERIA: Randomised controlled trials testing the effectiveness of interventions
      based on psychological models compared with educational, attention or no active
      intervention controls to improve adherence to oral hygiene in adults with either
      gingivitis or periodontitis. DATA COLLECTION AND ANALYSIS: Titles and abstracts
      of studies that were potentially relevant to the review were independently
      screened by two review authors. Those that were clearly ineligible were rejected.
      For the remaining studies, the full paper was reviewed by two review authors and
      where necessary further information was sought from the author to verify
      eligibility. Included studies were assessed on their quality using standard
      criteria. MAIN RESULTS: The review identified four studies (including 344
      participants) in which a psychological model or theory had been explicitly used
      as the basis for the design of the intervention. The overall quality of trials
      was low. Due to the hetereogeneity between studies, both in terms of outcome
      measures and psychological models adopted, a meta-analysis was not possible. The
      four studies adopted four different theoretical frameworks, though there was some
      overlap in that three of the studies incorporated elements of Operant and
      Classical Conditioning. Psychological interventions resulted in improved plaque
      scores in comparison to no intervention groups, and in one study in comparison to
      an attention control group. One study found decreased gingival bleeding in the
      active intervention group but no change in pocket depth or attachment loss after
      4 months. Psychological interventions were associated with improved self reported
      brushing and flossing in both studies which assessed these behaviours. Only one
      study explored the impact of psychological interventions on beliefs and
      attitudes, the psychological intervention, in comparison to educational and no
      intervention controls, showed improved self efficacy beliefs in relation to
      flossing, but no effect on dental knowledge or self efficacy beliefs in relation
      to tooth brushing. AUTHORS' CONCLUSIONS: There is tentative evidence from low
      quality studies that psychological approaches to behaviour management can improve
      oral hygiene related behaviours. However, the overall quality of the included
      trials was low. Furthermore, the design of the interventions was weak and
      limited, ignoring key aspects of the theories. Thus, there is a need for greater
      methodological rigour in the design of trials in this area.

PMID- 17443572
TI  - Low level laser therapy for nonspecific low-back pain.
AB  - BACKGROUND: Low-back pain (LBP) and related disabilities are major public health
      problems and a major cause of medical expenses, absenteeism and disablement. Low
      level laser therapy (LLLT) can be used as a therapeutic intervention for
      musculoskeletal disorders such as back pain. OBJECTIVES: To assess the effects of
      LLLT in patients with non-specific low-back pain and to explore the most
      effective method of administering LLLT for this disorder. SEARCH STRATEGY: We
      searched CENTRAL (The Cochrane Library 2005, Issue 2), MEDLINE and CINAHL from
      their start to January 2007 and EMBASE, AMED and PEDro from their start to 2005
      with no language restrictions. We screened references in the included studies and
      in reviews of the literature and conducted citation tracking of identified RCTs
      and reviews using Science Citation Index. We also contacted content experts.
      SELECTION CRITERIA: Only randomised controlled clinical trials (RCTs)
      investigating low level laser therapy as a light source treatment for non
      specific low-back pain were included. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed methodological quality using the criteria recommended by
      the Cochrane Back Review Group and extracted data. Consensus was used to resolve
      disagreements. Clinically and statistically homogeneous studies were pooled using
      the fixed-effect model; clinically homogeneous and statistically heterogeneous
      studies were pooled using the random-effects model. MAIN RESULTS: Six RCTs with
      reasonable quality were included in the review. All of them were published in
      English. There is some evidence of pain relief with LLLT, compared to sham
      therapy for subacute and chronic low-back pain. These effects were only observed
      at short-term and intermediate-term follow-ups. Long-term follow-ups were not
      reported. There was no difference between LLLT and comparison groups for pain
      related disability. There is insufficient evidence to determine the effectiveness
      of LLLT on antero-posterior lumbar range of motion compared to control group in
      short-term follow-up. The relapse rate in the LLLT group was significantly lower
      than in the control group at six months follow-up period according to the
      findings of two trials. AUTHORS' CONCLUSIONS: No side effects were reported.
      However, we conclude that there are insufficient data to draw firm conclusions.
      There is a need for further methodologically rigorous RCTs to evaluate the
      effects of LLLT compared to other treatments, different lengths of treatment,
      different wavelengths and different dosages. Comparison of different LLLT
      treatments will be more reasonable if dose calculation methods are harmonized.

PMID- 17443573
TI  - Immunoglobulins, vaccines or interferon for preventing cytomegalovirus disease in
      solid organ transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) is the most common virus causing disease and
      death in solid organ transplant recipients during the first six months post
      transplant. Previous systematic reviews have demonstrated the efficacy of
      antiviral medications used prophylactically or pre-emptively in preventing CMV
      disease. In this review the efficacy of older agents (immunoglobulins (IgG), anti
      CMV vaccines and interferon) are examined. OBJECTIVES: To assess the benefits and
      harms of IgG, anti CMV vaccines or interferon for preventing symptomatic CMV
      disease in solid organ transplant recipients. SEARCH STRATEGY: We searched the
      Cochrane Renal Group's Specialised Register, Cochrane Central Register of
      Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, reference
      lists and abstracts from conference proceedings without language restriction.
      Date of last search: December 2005 SELECTION CRITERIA: Randomised and quasi
      randomised controlled trials comparing IgG, anti CMV vaccine or interferon with
      placebo or no treatment, IgG alone or combined with antiviral medications with
      antiviral medications or IgG alone in recipients of any solid organ transplant.
      DATA COLLECTION AND ANALYSIS: Two of four authors independently assessed trial
      quality and extracted data from each trial. Statistical analyses were performed
      using the random effects model and results expressed as relative risk (RR) for
      dichotomous outcomes with 95% confidence intervals (CI). MAIN RESULTS: Thirty
      seven trials (2185 participants) were included in this review. There was no
      significant difference in the risk for CMV disease (16 trials, 770 patients: RR
      0.80, 95% CI 0.61 to 1.05), CMV infection (14 trials, 775 patients: RR 0.94, 95%
      CI 0.80 to 1.10) or all-cause mortality (8 trials, 502 patients: RR 0.57, 95% CI
      0.32 to 1.03) with IgG compared with placebo/no treatment. However IgG
      significantly reduced the risk of death from CMV disease (6 trials, 346 patients:
      RR 0.33, 95% CI 0.14 to 0.80). There was no difference in the risk for CMV
      disease (4 trials, 298 patients: RR 1.17, 95% CI 0.74 to 1.86), CMV infection (4
      trials, 298 patients: RR 1.16, 95% CI 0.89 to 1.52) or all-cause mortality (2
      trials, 217 patients: RR 0.92, 95% CI 0.37 to 2.29) between antiviral medication
      combined with IgG and antiviral medication alone. There was no significant
      difference in the risk of CMV disease with anti CMV vaccine or interferon
      compared with placebo or no treatment. AUTHORS' CONCLUSIONS: Currently there are
      no indications for IgG in the prophylaxis of CMV disease in recipients of solid
      organ transplants.

PMID- 17443574
TI  - Steroids for acute sinusitis.
AB  - BACKGROUND: Acute sinusitis is a common reason for primary care visits. It causes
      significant symptoms and often results in time off work and school. OBJECTIVES:
      We examined whether intranasal corticosteroids (INCS) are effective in relieving
      symptoms of acute sinusitis. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (The Cochrane Library Issue 4, 2006), MEDLINE
      (January 1966 to December 2006), EMBASE (1990 to June 2006) and bibliographies of
      included studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) were
      considered eligible if they compared INCS treatment to placebo treatment of a
      control group for acute sinusitis; acute sinusitis was defined by clinical
      diagnosis and confirmed by radiological evidence or by nasal endoscopy. The
      primary outcome was the proportion of participants with either resolution or
      improvement of symptoms. Secondary outcomes were any adverse events that required
      discontinuation of treatment, drop-outs before the end of the study, rates of
      relapse, complications and return to school or work. DATA COLLECTION AND
      ANALYSIS: Two review authors independently extracted the data, assessed trial
      quality and resolved discrepancies by consensus. MAIN RESULTS: Four studies with
      1943 participants met the inclusion criteria. The trials were well designed,
      double-blind, placebo controlled in which the included participants had acute
      sinusitis. The treatment assigned was INCS versus control treatment for 15 or 21
      days. The rates of loss to follow up in the studies were 7%, 11%, 41% and 10%.
      When the results from the three trials included in the meta-analysis were
      combined, participants receiving INCS were more likely to have resolution or
      improvement of symptoms than those receiving placebo (73% versus 66.4%; RR 1.11;
      95% CI 1.04 to 1.18). Higher doses of INCS had a stronger effect on improvement
      or complete relief of symptoms: for mometasone furoate (MFNS) 400 mcg versus 200
      mcg, (RR 1.10; 95% CI 1.02 to 1.18 versus RR 1.04; 95% CI 0.98 to 1.11). No
      significant adverse events were reported and there was no significant difference
      in the drop-out and recurrence rate for the two treatment groups and for groups
      receiving higher doses of INCS. AUTHORS' CONCLUSIONS: For acute sinusitis
      confirmed by radiology or nasal endoscopy, current evidence is limited, but
      supports the use of INCS as a monotherapy or as an adjuvant therapy to
      antibiotics. Clinicians should weigh the modest but clinically important benefits
      against possible minor adverse events when prescribing therapy.

PMID- 17443575
TI  - Interventions to improve hand hygiene compliance in patient care.
AB  - BACKGROUND: Health care-associated infection is a major cause of morbidity and
      mortality. Hand hygiene is regarded as an effective preventive measure.
      OBJECTIVES: To assess the short and longer-term success of strategies to improve
      hand hygiene compliance and to determine whether a sustained increase in hand
      hygiene compliance can reduce rates of health care-associated infection. SEARCH
      STRATEGY: We conducted electronic searches of: the Cochrane Central Register of
      Controlled Trials; the Cochrane Effective Practice and Organisation of Care Group
      specialised register of trials; MEDLINE; PubMed; EMBASE; CINAHL; and the BNI. All
      databases were searched to July 2006; MEDLINE was searched from 1980, CINAHL from
      its inception, and the remainder from 1990 until July 2006. SELECTION CRITERIA:
      Randomised controlled trials; controlled clinical trials; controlled before and
      after studies; and interrupted time series analyses meeting explicit entry and
      quality criteria used by the Cochrane Effective Practice and Organisation of Care
      Group. Studies reporting proxy indicators of hand hygiene compliance were
      considered. Studies to promote compliance with universal precautions were
      included providing data relating specifically to hand hygiene were presented
      separately. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted
      data and assessed data quality. MAIN RESULTS: Two studies met the criteria for
      review. One was a randomised controlled trial. The other was a controlled before
      and after study. Both were poorly controlled. Statistically significant post
      intervention increase in hand washing was reported in one study up to four months
      after the intervention. In the other there was no post-intervention increase in
      hand hygiene compliance. AUTHORS' CONCLUSIONS: There is little robust evidence to
      inform the choice of interventions to improve hand hygiene. It appears that
      single interventions based on short, 'one off' teaching sessions are unlikely to
      be successful, even short-term. There is a need to undertake methodologically
      robust research to explore the effectiveness of soundly designed interventions to
      increase hand hygiene compliance.

PMID- 17443576
TI  - Psychotropic analgesic nitrous oxide for alcoholic withdrawal states.
AB  - BACKGROUND: Alcoholism is a global problem with 5-10% of the world's population
      demonstrating alcohol-related diseases. One of the most severe consequences of
      alcohol dependence is the withdrawal syndrome, for which benzodiazepines are the
      most popular current treatment. An alternative method to benzodiazepine employs
      psychotropic analgesic nitrous oxide (PAN). OBJECTIVES: To assess the effects of
      PAN for treating alcohol withdrawal states SEARCH STRATEGY: We searched the
      Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2,
      2005), MEDLINE, EMBASE, CINAHL (all to May 2005). We scanned internet websites,
      reference lists of relevant articles and abstracts of the international
      Conferences on Alcoholism. We contacted researchers in the field and industry to
      identify unpublished trials. No language and publication restrictions. SELECTION
      CRITERIA: Randomised controlled trials including voluntary participants dependent
      on alcohol. PAN was compared to oxygen and/or benzodiazepine regimens. DATA
      COLLECTION AND ANALYSIS: Two authors independently assessed the methodological
      quality of the trials and extracted data. MAIN RESULTS: Five studies, 212
      participants, were included. PAN showed improvement of symptoms (RR 1.35; 95% CI
      1.01 to 1.79), of the amount and duration of sedative medication and of
      psychomotor function (WMD -8.71; 95% CI -13.71 to -3.71). At one hour post
      intervention, no significant differences were found for depression (WMD -2.40;
      95% CI -8.70 to 3.89) and anxiety (WMD -3.70; 95% CI -10.53 to 3.12). None of the
      included studies reported any significant adverse effects of any treatment.
      AUTHORS' CONCLUSIONS: Results indicate that PAN may be an effective treatment of
      the mild to moderate alcoholic withdrawal state. The rapidity of the therapeutic
      effect of PAN therapy coupled with the minimal sedative requirements, may enable
      patients to enter the psychological treatment phase more quickly than those on
      sedative regimens, accelerating the patients recovery. Our review does not
      provide strong evidence due to the small sample sizes of the included trials.
      Neither does the review indicate any causes for concern that PAN is more harmful
      than the benzodiazepines. Clinicians wishing to use PAN may initially wish to do
      so within trial settings. Further high quality trials should be done to confirm
      these findings and to investigate whether the PAN therapy has fewer adverse
      effects than other treatments for the alcohol withdrawal states. Studies to
      investigate the possible cost-effectiveness of PAN by reducing costly hospital
      admissions and decreasing post administration supervision also need to be
      performed.

PMID- 17443577
TI  - Colony stimulating factors (including erythropoietin, granulocyte colony
      stimulating factor and analogues) for stroke.
AB  - BACKGROUND: Colony stimulating factors (CSFs), also called haematopoietic growth
      factors, regulate bone marrow production of circulating red and white cells, and
      platelets. They have been shown to be neuroprotective in experimental stroke.
      Some CSFs also mobilise the release of bone marrow stem cells into the
      circulation. OBJECTIVES: To assess the effects of CSFs on functional outcome and
      haematology measures in patients with acute or subacute stroke. SEARCH STRATEGY:
      We searched the Cochrane Stroke Group Trials Register (last searched November
      2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library Issue 2, 2006), MEDLINE (1985 to June 2006), EMBASE (1985 to June 2006),
      and Science Citation Index (1985 to June 2006). In an attempt to identify further
      published, unpublished and ongoing trials we contacted manufacturers and
      principal investigators of trials (last contacted 2006). We also searched
      reference lists of relevant articles and reviews. SELECTION CRITERIA:
      Unconfounded randomised controlled trials recruiting patients with acute or
      subacute ischaemic or haemorrhagic stroke were included. CSFs included stem cell
      factor (SCF), erythropoietin (EPO), granulocyte colony stimulating factor (G
      CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage
      colony stimulating factor (M-CSF, CSF-1), and thrombopoietin (TPO), or analogues
      of these. The primary outcome was functional outcome (assessed as combined death
      or disability and dependency using scales such as the modified Rankin Scale or
      Barthel Index) at the end of the trial. Secondary outcomes included safety at the
      end of treatment (death, impairment, deterioration, extension or recurrence),
      death at the end of follow up, and haematology measures (blood counts at or
      around day seven after treatment commenced). DATA COLLECTION AND ANALYSIS: Two
      review authors independently extracted data and assessed trial quality. Study
      authors were contacted for additional information. MAIN RESULTS: No large trials
      were identified. EPO therapy was associated with a non-significant reduction in
      neurological impairment in one small trial (n = 40 participants) but had no
      significant effect on haematological measures. G-CSF was associated with a non
      significant reduction in combined death and dependency in two small trials (n =
      46 participants) although there was substantial heterogeneity in this result. G
      CSF significantly elevated white cell count in three trials (n = 91). Further
      small trials of EPO and G-CSF are ongoing. AUTHORS' CONCLUSIONS: No large trials
      of EPO, G-CSF or other colony stimulating factors have been performed and it is
      too early to know whether CSFs improve functional outcome.

PMID- 17443578
TI  - Interventions for preventing venous thromboembolism in adults undergoing knee
      arthroscopy.
AB  - BACKGROUND: Knee arthroscopy is a frequent surgical procedure. Arthroscopy
      procedures are considered minimally invasive. However, some patients will need
      extended surgical time, suffer injury and immobilization thus increasing the risk
      for thromboembolic events. Incidence of deep venous thrombosis (DVT) in patients
      undergoing knee arthroscopy is reported to be from 0.6% to 17.9% depending on the
      diagnostic method used. Different approaches are available for thromboprophylaxis
      (mechanical or pharmacological). OBJECTIVES: To assess the effectiveness and
      safety of thromboprophylaxis to reduce the incidence of DVT in patients
      undergoing knee arthroscopy. SEARCH STRATEGY: We searched the Cochrane Peripheral
      Vascular Diseases Group Specialized Register (last searched October 2006) the
      CENTRAL (last searched Issue 4, 2006), MEDLINE (1966 to 2006), EMBASE (1980 to
      2006), and Lilacs (1988 to 2006). We contacted specialists known to be involved
      in phlebology and interested in post thrombotic syndrome for details of
      unpublished and ongoing trials. SELECTION CRITERIA: Randomized clinical trials
      (RCTs) and controlled clinical trials (CCTs), whether blinded or not (i.e. double
      blinded, single blinded or unblinded) of all type of interventions, whether
      mechanical or pharmacological, single or in combination, used to prevent DVT in
      males and females over 18 years old undergoing knee arthroscopy. There was no
      restriction on language. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trial quality and extracted data. Study authors were contacted for
      additional information. MAIN RESULTS: Four trials involving 527 predominantly
      male participants were included. The main weakness of the studies was the lack of
      correct stratification of the arthroscopic intervention. The relative risk (RR)
      of thrombotic events was 0.20 (95% confidence interval (CI); 0.07 to 0.57)
      comparing any type of low molecular weight heparin (LMWH) versus placebo. All
      thrombotic events but one (pulmonary embolism in the LMWH group) were distal
      venous thrombosis. Adverse events were most common in the intervention group than
      in the control group, RR 2.11 (95% CI 1.26 to 3.55). There were 66 episodes of
      adverse events. The number needed to harm was 20 for any adverse events. AUTHORS'
      CONCLUSIONS: This meta-analysis suggests that LMWH reduces the incidence of
      distal DVT diagnosed by sonogram. The clinical benefit of this is uncertain. No
      strong evidence was found to conclude thromboprophylaxis is effective to prevent
      thromboembolic events and safe, in people with unknown risk factors for
      thrombosis, undergoing knee arthroscopy.

PMID- 17443579
TI  - Recompression and adjunctive therapy for decompression illness.
AB  - BACKGROUND: Decompression illness (DCI) is due to bubble formation in the blood
      or tissues following the breathing of compressed gas. Clinically, DCI may range
      from a trivial illness to loss of consciousness, death or paralysis.
      Recompression is the universally accepted standard for the treatment of DCI. When
      recompression is delayed, a number of strategies have been suggested in order to
      improve the outcome. OBJECTIVES: To examine the effectiveness and safety of both
      recompression and adjunctive therapies in the treatment of DCI. SEARCH STRATEGY:
      We searched CENTRAL (The Cochrane Library 2005, Issue 2); MEDLINE (1966 to August
      2005); CINAHL (1982 to August 2005); EMBASE (1980 to August 2005); the Database
      of Randomised Controlled Trials in Hyperbaric Medicine (August 2005), and hand
      searched journals and texts. SELECTION CRITERIA: We included randomized
      controlled trials that compared the effect of any recompression schedule or
      adjunctive therapy with a standard recompression schedule. We applied no language
      restrictions. DATA COLLECTION AND ANALYSIS: Three authors extracted the data
      independently. We assessed each trial for internal validity and resolved
      differences by discussion. Data was entered into RevMan 4.2. MAIN RESULTS: Two
      randomized controlled trials satisfied the inclusion criteria. Pooling of data
      was not possible. In one study there was no evidence of improved effectiveness
      with the addition of a non-steroidal anti-inflammatory drug (tenoxicam) to
      routine recompression therapy (at six weeks: relative risk (RR) 1.04, 95%
      confidence interval (CI) 0.90 to 1.20, P = 0.58) but there was a reduction in the
      number of compressions required when tenoxicam was added (P = 0.01, 95% CI 0 to
      1). In the other study, the odds of multiple recompressions was lower with a
      helium and oxygen (heliox) table compared to an oxygen treatment table (RR 0.56,
      95% CI 0.31 to 1.00, P = 0.05). AUTHORS' CONCLUSIONS: Recompression therapy is
      standard for the treatment of DCI, but there is no randomized controlled trial
      evidence. Both the addition of an NSAID or the use of heliox may reduce the
      number of recompressions required, but neither improves the odds of recovery. The
      application of either of these strategies may be justified. The modest number of
      patients studied demands a cautious interpretation. Benefits may be largely
      economic and an economic analysis should be undertaken. There is a case for large
      randomized trials of high methodological rigour in order to define any benefit
      from the use of different breathing gases and pressure profiles during
      recompression therapy.

PMID- 17443580
TI  - Fish oil for kidney transplant recipients.
AB  - BACKGROUND: Calcineurin inhibitors used in kidney transplantation for
      immunosuppression have adverse effects that may contribute to nephrotoxicity and
      increased cardiovascular risk profile. Fish oils are rich in very long chain
      omega-3 fatty acids, which may reduce nephrotoxicity by improving endothelial
      function and reduce rejection rates through their immuno-modulatory effects. They
      may also modify the cardiovascular risk profile. Hence, fish oils may potentially
      prolong graft survival and reduce cardiovascular mortality. OBJECTIVES: To assess
      the benefits and harms of fish oil supplementation on kidney transplant
      recipients on a calcineurin inhibitor-based immunosuppressive regimen. SEARCH
      STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL
      in The Cochrane Library, issue 2 2005), MEDLINE (1966-April 2005) and EMBASE
      (1980-April 2005). SELECTION CRITERIA: All randomised controlled trials (RCTs)
      and quasi-RCTs of fish oils in kidney transplant recipients on a calcineurin
      inhibitor-based immunosuppressive regimen. RCTs of fish oil versus statins were
      included. DATA COLLECTION AND ANALYSIS: Data was extracted and the quality of
      studies assessed by two authors, with differences resolved by discussion with a
      third independent author. Dichotomous outcomes were reported as relative risk
      (RR) and continuous outcome measures were reported as the mean difference (MD)
      with 95% confidence intervals using the random effects model. Heterogeneity was
      assessed using a Chi(2) test on n-1 degrees of freedom and the I(2) statistic.
      Data not suitable for pooling were tabulated and described. MAIN RESULTS: Sixteen
      studies (733 patients) were suitable for analysis. Fish oil did not significantly
      affect patient or graft survival, acute rejection rates, calcineurin inhibitor
      toxicity or renal function, when compared to placebo. Fish oil treatment was
      associated with a lower diastolic blood pressure (MD 4.5 mmHg; P = 0.004)
      compared to placebo. Patients receiving fish oil for more than six months had a
      modest increase in HDL (MD 0.12 mmol/L; P = 0.01) compared to placebo. Fish oil
      effects on lipids were not significantly different from low-dose statins. There
      was insufficient data to analyse cardiovascular outcomes. Fishy aftertaste and
      gastrointestinal upset were common but did not result in significant patient drop
      out. AUTHORS' CONCLUSIONS: There is insufficient evidence from currently
      available RCTs to recommend fish oil therapy to improve renal function, rejection
      rates, patient survival or graft survival. The improvements in HDL cholesterol
      and diastolic blood pressure were too modest to recommend routine use. To
      determine a benefit in clinical outcomes, future RCTs will need to be adequately
      powered with these outcomes in mind.

PMID- 17443581
TI  - Selective estrogen receptor modulators (SERMs) for uterine leiomyomas.
AB  - BACKGROUND: Uterine fibroids are benign tumors that arise from individual smooth
      muscle cells of the uterus. Selective estrogen receptor modulators (SERMs) are ER
      ligands that act as estrogens in some tissues, while blocking estrogen action in
      others. There have been many clinical studies of various SERMs for uterine
      fibroid. However, their effectiveness is controversial. OBJECTIVES: To evaluate
      the evidence for the effectiveness and safety of selective estrogen receptor
      modulators in women with uterine fibroids. SEARCH STRATEGY: We searched The
      Cochrane Library, MEDLINE, the Register of Chinese trials developed by the
      Chinese Cochrane Centre, and the Chinese Med Database, Chinese Biomedical Disc
      (CBMDisc 1978 to July 2004); VIP (1989 to October 2005)); China National
      Knowledge Infrastructure (CNKI 1994 to 2003) in October 2005. We hand searched a
      number of journals, and searched reference lists, databases of ongoing trials and
      the Internet. SELECTION CRITERIA: We included randomized controlled studies of
      selective estrogen receptor modulators versus other forms of medical therapy or
      placebo in women in the reproductive age (18 to 45 years old) with confirmed
      uterine fibroid. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted data and assessed trial quality. As the studies identified were not
      sufficiently similar and not of sufficient quality, we did not do a meta-analysis
      but summarized the data in a narrative format. MAIN RESULTS: Three studies
      involving 215 participants were included, trial size varied from 25 to 100.
      Comparison interventions included no treatment, Poly vitamins, and leuprolide
      acetate depot plus raloxifene versus leuprolide plus placebo tablet. There was a
      tendency towards fibroid reduction with selective estrogen receptor modulators
      (SERMs), although this was not significant in all studies. All three studies
      mentioned adverse reactions but no detailed data were acquired in the included
      studies. AUTHORS' CONCLUSIONS: There is no evidence from the limited number of
      studies that SERMs reduce the size of fibroids or improve clinical outcomes.
      Further studies are required to establish evidence of benefit of SERMs in
      treating women with uterine fibroids.

PMID- 17443582
TI  - Specialised antenatal clinics for women with a multiple pregnancy to improve
      maternal and infant outcomes.
AB  - BACKGROUND: Regular antenatal care for women with a multiple pregnancy is
      accepted practice, and while most women have an increase in the number of
      antenatal visits, there is no consensus as to what constitutes optimal care.
      'Specialised' antenatal clinics have been advocated as a way of improving
      outcomes for women and their infants. OBJECTIVES: To assess, using the best
      available evidence, the benefits and harms of 'specialised' antenatal clinics
      compared with 'standard' antenatal care for women with a multiple pregnancy.
      SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (October 2006), the Cochrane Central Register of Controlled Trials
      (CENTRAL)(The Cochrane Library 2005, Issue 4), and PubMed (January 1966 to
      January 2006). SELECTION CRITERIA: Randomised controlled trials with reported
      data that compared outcomes in mothers and babies who received 'specialised'
      antenatal care with outcomes in mothers and babies who received 'standard'
      antenatal care. DATA COLLECTION AND ANALYSIS: Both review authors independently
      assessed trial quality and extracted data. MAIN RESULTS: There are no included
      studies. AUTHORS' CONCLUSIONS: There is no information available from randomised
      controlled trials to support the role of 'specialised' antenatal clinics for
      women with a multiple pregnancy compared with 'standard' antenatal care in
      improving maternal and infant health outcomes. The value of 'specialised'
      multiple pregnancy clinics in improving health outcomes for women and their
      infants requires evaluation in appropriately powered and designed randomised
      controlled trials.

PMID- 17443583
TI  - Psychological treatments versus treatment as usual for obsessive compulsive
      disorder (OCD).
AB  - BACKGROUND: Obsessive compulsive disorder (OCD) is a chronic anxiety disorder
      associated with significant morbidity, social impairment and lower quality of
      life. Psychological treatments are a frequently used approach for OCD.
      OBJECTIVES: To perform a systematic review of randomised trials of psychological
      treatments for obsessive compulsive disorder in comparison with treatment as
      usual. SEARCH STRATEGY: We conducted an electronic search of CCDANCTR-Studies
      (31/10/2006), and other databases. We searched reference lists, and contacted
      experts in the field. SELECTION CRITERIA: Published and unpublished randomised
      trials of psychological treatments versus treatment as usual for adults with a
      diagnosis of OCD DATA COLLECTION AND ANALYSIS: Two review authors worked
      independently throughout the selection of trials and data extraction. Findings
      were compared and disagreements were discussed with a third review author. Full
      data extraction, using a standardised data extraction sheet, was performed on all
      studies included in the review. Results were synthesised using Review Manager
      software. For dichotomous data, odds ratios were calculated. For continuous data,
      effect sizes were obtained and the standardised mean difference, with 95%
      confidence intervals, was calculated. Fixed and random effects models were used
      to pool the data. Reasons for heterogeneity in studies were explored and
      sensitivity analyses were performed by excluding trials of lower quality. MAIN
      RESULTS: Eight studies (11 study comparisons) were identified, all of which
      compared cognitive and/or behavioural treatments versus treatment as usual
      control groups. Seven studies (ten comparisons) had usable data for meta
      analyses. These studies demonstrated that patients receiving any variant of
      cognitive behavioural treatment exhibited significantly fewer symptoms post
      treatment than those receiving treatment as usual (SMD -1.24, 95% CI -1.61 to 
      0.87, I(2) test for heterogeneity 33.4%). Different types of cognitive and/or
      behavioural treatments showed similar differences in effect when compared with
      treatment as usual. The overall treatment effect appeared to be influenced by
      differences in baseline severity. AUTHORS' CONCLUSIONS: The findings of this
      review suggest that psychological treatments derived from cognitive behavioural
      models are an effective treatment for adult patients with obsessive compulsive
      disorder. Larger high quality randomised controlled trials involving longer
      follow up periods are needed, to further test cognitive behavioural treatments,
      and other psychological approaches, in comparison to each other and control
      conditions. Future trials should examine the predictors of response to each
      treatment, and also conduct cost-effectiveness evaluations.

PMID- 17443584
TI  - Ovarian stimulation protocols (anti-oestrogens, gonadotrophins with and without
      GnRH agonists/antagonists) for intrauterine insemination (IUI) in women with
      subfertility.
AB  - BACKGROUND: Intrauterine insemination (IUI) combined with ovarian
      hyperstimulation (OH) has been demonstrated to be an effective form of treatment
      for subfertile couples. Several ovarian stimulation protocols combined with IUI
      have been proposed, but it is still not clear which stimulation protocol and
      which dose is the most cost-effective. OBJECTIVES: To evaluate ovarian
      stimulation protocols for intrauterine insemination for all indications. SEARCH
      STRATEGY: We searched for all publications which described randomised controlled
      trials comparing different ovarian stimulation protocols followed by IUI. We
      searched the Menstrual Disorders and Subfertility Group's Central register of
      Controlled Trials (CENTRAL). We searched the electronic databases of MEDLINE
      (January 1966 to present) and EMBASE (1980 to present). SELECTION CRITERIA:
      Randomised controlled trials only were considered for inclusion in this review.
      Trials comparing different ovarian stimulation protocols combined with IUI were
      selected and reviewed in detail. DATA COLLECTION AND ANALYSIS: Two independent
      review authors independently assess trial quality and extracted data. MAIN
      RESULTS: Forty three trials involving 3957 women were included. There were 11
      comparisons in this review. Pregnancy rates are reported here since results of
      live birth rates were lacking. Seven studies (n = 556) were pooled comparing
      gonadotrophins with anti-oestrogens showing significant higher pregnancy rates
      with gonadotrophins (OR 1.8, 95% CI 1.2 to 2.7). Five studies (n = 313) compared
      anti-oestrogens with aromatase inhibitors reporting no significant difference (OR
      1.2 95% CI 0.64 to 2.1). The same could be concluded comparing different types of
      gonadotrophins (9 studies included, n = 576). Four studies (n = 391) reported the
      effect of adding a GnRH agonist which did not improve pregnancy rates (OR 0.98
      95% CI 0.6 to 1.6), although it resulted in significant higher multiple pregnancy
      rates (OR 2.9 95% CI 1.0 to 8). Data of three studies (n = 299) showed no
      convincing evidence of adding a GnRH antagonist to gonadotrophins (OR 1.5 95% CI
      0.83 to 2.8). The results of two studies (n = 297) reported no evidence of
      benefit in doubling the dose of gonadotrophins (OR 1.2 95% 0.67 to 1.9) although
      the multiple pregnancy rates and OHSS rates were increased. For the remaining
      five comparisons only one or none studies were included. AUTHORS' CONCLUSIONS:
      Robust evidence is lacking but based on the available results gonadotrophins
      might be the most effective drugs when IUI is combined with ovarian
      hyperstimulation. When gonadotrophins are applied it might be done on a daily
      basis. When gonadotrophins are used for ovarian stimulation low dose protocols
      are advised since pregnancy rates do not differ from pregnancy rates which result
      from high dose regimen, whereas the chances to encounter negative effects from
      ovarian stimulation such as multiples and OHSS are limited with low dose
      gonadotrophins. Further research is needed for each comparison made.

PMID- 17443585
TI  - Oxygen therapy during exercise training in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Exercise training within the context of pulmonary rehabilitation
      improves outcomes of exercise capacity, dyspnea and health-related quality of
      life in individuals with chronic obstructive pulmonary disease (COPD).
      Supplemental oxygen in comparison to placebo increases exercise capacity in
      patients performing single-assessment exercise tests. The addition of
      supplemental oxygen during exercise training may enable individuals with COPD to
      tolerate higher levels of activity with less exertional symptoms, ultimately
      improving quality of life. OBJECTIVES: To determine how supplemental oxygen in
      comparison to control (compressed air or room air) during the exercise-training
      component of a pulmonary rehabilitation program affects exercise capacity,
      dyspnea and health-related quality of life in individuals with COPD. SEARCH
      STRATEGY: All records in the Cochrane Airways Group Specialized Register of
      trials coded as 'COPD' were searched using the following terms: (oxygen* or O2*)
      AND (exercis* or train* or rehabilitat* or fitness* or physical* or activ* or
      endur* or exert* or walk* or cycle*). Searching the Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE and CINAHL
      databases identified studies. The last search was carried out in June 2006.
      SELECTION CRITERIA: Only randomized controlled trials (RCTs) comparing oxygen
      supplemented exercise training to non-supplemented exercise training (control
      group) were considered for inclusion. Participants were 18 years or older,
      diagnosed with COPD and did not meet criteria for long-term oxygen therapy. No
      studies with mixed populations (pulmonary fibrosis, cystic fibrosis, etc) were
      included. Exercise training was greater than or equal to three weeks in duration
      and included a minimum of two sessions a week. DATA COLLECTION AND ANALYSIS: Two
      review authors independently selected trials for inclusion in the review and
      extracted data. Weighted mean differences (WMD) with 95% confidence intervals
      (CI) were calculated using a random-effects model. Missing data were requested
      from authors of primary studies. MAIN RESULTS: Five RCTs met the inclusion
      criteria. The maximum number of studies compared in the meta-analysis was three
      (31 on oxygen versus 32 control participants), because all included studies did
      not measure the same outcomes. When two studies were pooled, statistically
      significant improvements of oxygen-supplemented exercise training were found in
      constant power exercise time, WMD 2.68 minutes (95% CI 0.07 to 5.28 minutes).
      Supplemental oxygen increased the average exercise time from 6 to 14 minutes; the
      control intervention increased average exercise time from 6 to 12 minutes.
      Constant power exercise end-of-test Borg score (on a scale from 1 to 10) also
      showed statistically significant improvements with oxygen-supplemented exercise
      training, WMD -1.22 units (95% CI -2.39 to -0.06). One study showed a significant
      improvement in the change of Borg score after the shuttle walk test, by -1.46
      units (95% CI -2.72 to -0.19). There were no significant differences in maximal
      exercise outcomes, functional exercise outcomes (six-minute walk test), shuttle
      walk distance, health-related quality of life or oxygenation status. According to
      the GRADE system most outcomes were rated as low quality because they were
      limited by study quality. AUTHORS' CONCLUSIONS: This review provides little
      support for oxygen supplementation during exercise training for individuals with
      COPD, but the evidence is very limited. Studies with larger number of
      participants and strong design are required to permit strong conclusions,
      especially for functional outcomes such as symptom alleviation, health-related
      quality of life and ambulation.

PMID- 17443586
TI  - Yizhi capsule for vascular dementia.
AB  - BACKGROUND: Vascular dementia (VD) is a syndrome or diagnosis that has different
      causes and clinical manifestations relating to several different vascular
      mechanisms and changes in the brain. Some traditional Chinese herbal medicines
      were developed for treating VD. DH: Yizhi capsule is one such herbal concoction
      which is reported to improve clinical symptoms significantly. The efficacy and
      adverse effects of Yizhi capsule need to be reviewed systematically and assessed
      critically to inform clinical practice and guide the continued search for new
      treatment regimens. OBJECTIVES: To assess the effectiveness and possible adverse
      events of 'Yizhi capsule' in treating vascular dementia. SEARCH STRATEGY: The
      Cochrane Dementia and Cognitive Improvement Group's Specialised Register was
      searched on 18 September 2006 using the terms yi-zhi, "yi zhi" and yizhi. This
      database contains trial references from major health care databases and ongoing
      trial database and is up to date. In addition the review authors searched a
      variety of Chinese databases. SELECTION CRITERIA: Randomised, placebo controlled
      trials in which patients with vascular dementia were treated with 'Yizhi capsule'
      were included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed
      trial quality and extracted data. We telephoned study authors for missing
      information as to whether treatment allocation was randomised and other
      methodological details. MAIN RESULTS: No studies were found that met the
      inclusion criteria. We identified nine references to trials which included the
      term 'Yizhi capsule' in the description of the interventions. Two study authors
      were contacted by telephone and we discovered that the allocation methods they
      had used were not actually randomised. Four references were describing the same
      study. Three studies were excluded because 'positive drugs' were used as a
      control. AUTHORS' CONCLUSIONS: There is no evidence from randomised controlled
      trials to support or proscribe against the use of 'Yizhi capsule' as a treatment
      for vascular dementia.

PMID- 17443587
TI  - Physical activity programs for promoting bone mineralization and growth in
      preterm infants.
AB  - BACKGROUND: Lack of physical stimulation may contribute to metabolic bone disease
      of preterm infants resulting in poor bone mineralization and growth. Physical
      activity programs in the presence of adequate nutrition might help to promote
      bone mineralization and growth. OBJECTIVES: The primary objective of this review
      was to assess whether physical activity programs in preterm infants improve bone
      mineralization and growth and reduce the risk of fractures. SEARCH STRATEGY:
      Following the standard search strategy of the Cochrane Neonatal Review Group, a
      search was conducted in September 2006 including PubMed, EMBASE, CINAHL, the
      Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library,
      Issue 3, 2006), cross-references and handsearching of abstracts of the Society
      for Pediatric Research and the International Journal of Sports Medicine. No
      language restrictions were applied. SELECTION CRITERIA: Randomized and quasi
      randomized controlled trials comparing physical activity programs (extension and
      flexion, range-of-motion exercises for several minutes a day several days per
      week for at least two weeks) to no organized physical activity programs in
      preterm infants. Eligible studies included those that provided physical activity
      for the experimental group, with or without massage and/or tactile stimulation
      for both experimental and control groups, as well as information on at least one
      outcome of interest. DATA COLLECTION AND ANALYSIS: Two review authors
      independently performed searches and extracted data. All three review authors
      were involved in selection and assessment of quality of studies. The statistical
      methods included relative risk (RR), risk difference (RD) and number needed to
      treat (NNT) for dichotomous outcomes and weighted mean difference (WMD) for
      continuous outcomes, reported with 95% confidence intervals (CI). Heterogeneity
      was estimated by the I(2) statistic. A fixed effect model was used to pool data
      for meta-analyses. MAIN RESULTS: Six trials enrolling 169 preterm infants
      (gestational age 26 to 34 weeks) were included in this review. All were small (N
      = 20 - 49) single center studies evaluating daily physical activity for 3.5 to 4
      weeks during initial hospitalization. The methodological quality and reporting of
      all trials was poor. None of them stated the methods of concealment of patient
      allocation, the method of randomization or attempted blinding of the
      intervention. Only two trials attempted blinding of outcome assessors for
      outcomes relevant to this review. Two trials (N = 55) demonstrated moderate short
      term benefits of physical activity on bone mineralization at completion of the
      physical activity program. Data was not pooled for meta-analyses due to
      methodological differences. The only trial (N = 20) assessing long-term effects
      on bone mineralization showed no effect of physical activity administered during
      initial hospitalization on bone mineralization at 12 months corrected age. Meta
      analysis from three trials (N = 78) demonstrated an effect of physical activity
      on daily weight gain (WMD 2.77 g/kg/d, 95% CI 1.62, 3.92). Data from two trials
      (N = 58) showed no effect on linear growth (WMD -0.04 cm/week, 95% CI -0.19,
      0.11) or head growth (WMD -0.03 cm/week, 95% CI -0.14, 0.09) during the study
      period. The I(2) statistic suggested heterogeneity on the analysis of linear
      growth (p = 0.006, I(2) = 86.9%). None of the trials assessed fractures or other
      outcomes relevant to this review. Data was insufficient for subgroup analyses
      based on birth weight and calcium/phosphorus intake. AUTHORS' CONCLUSIONS: There
      is weak evidence from six small randomized trials of poor methodological and
      reporting quality that physical activity programs might promote moderate short
      term weight gain and bone mineralization in preterm infants. The clinical
      importance of these findings is questionable given the small effect size and low
      baseline risk of poor bone mineralization and growth in study participants. Data
      is inadequate to assess harm or long term effects. Current evidence does not
      justify the standard use of physical activity programs in preterm infants.
      Further evaluation of this intervention in well designed trials incorporating
      extremely low birth weight infants who are at high risk of osteopenia is
      required. Future trials should report on adverse events and long term outcomes
      including fractures, growth, bone mineralization, skeletal deformities and
      neurodevelopmental impairment. These trials should address the possibility that
      nutritional intake (calories, protein, calcium, phosphorus) might modify the
      effects of physical activity.

PMID- 17443588
TI  - Bicycle helmet legislation for the uptake of helmet use and prevention of head
      injuries.
AB  - BACKGROUND: Evidence exists to suggest that bicycle helmets may reduce the risk
      of head injuries to cyclists, however helmets are not uniformly worn by all
      bicycle users. Legislation has been enacted in some countries to mandate helmet
      use by cyclists, however the issue remains controversial with opponents arguing
      that this may inhibit people from bicycle riding and thus from gaining the
      associated health benefits, or that other countermeasures may have been
      responsible for decline in head injuries. OBJECTIVES: To assess the effects of
      bicycle helmet legislation on bicycle-related head injuries and helmet use, and
      the occurrence of unintended adverse consequences. SEARCH STRATEGY: We searched
      CENTRAL, the Cochrane Injuries Group's specialised register, MEDLINE, EMBASE,
      TRANSPORT and other specialist electronic databases, up to February 2006. In
      addition we searched government websites, handsearched selected journals and
      examined the reference lists of selected publications. SELECTION CRITERIA: We
      included studies that reported changes in either the number of head injuries,
      helmet use or bicycle use post- versus pre-legislation. Only studies that
      included a concurrent control group and which reported on the effect of
      legislation implemented at either the country, state or province wide level were
      included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data
      and assessed methodological quality. The data were not appropriate for meta
      analysis, thus the results of the included studies have been reviewed
      narratively. MAIN RESULTS: Five studies, all from North America, met the
      inclusion criteria. For each of the studies, bicycle helmet legislation had been
      enacted for children only. Adults were used as controls in four of the studies,
      whilst jurisdictions with no helmet legislation were used as controls in the
      fifth. Three of the studies reported on changes in head injury rates and three
      reported on changes in helmet use. There were no included studies reporting
      change in bicycle use or other adverse consequences of legislation. In two
      studies, statistically significant decreases in head injuries were reported
      following the implementation of helmet legislation compared with controls, whilst
      one reported a non-statistically significant decline. Bicycle helmet use
      increased statistically significantly post-legislation in all three of the
      studies reporting on helmet use. AUTHORS' CONCLUSIONS: Bicycle helmet legislation
      appears to be effective in increasing helmet use and decreasing head injury rates
      in the populations for which it is implemented. However, there are very few high
      quality evaluative studies that measure these outcomes, and none that reported
      data on an possible declines in bicycle use.

PMID- 17443589
TI  - Fluid replacement therapy for acute episodes of pain in people with sickle cell
      disease.
AB  - BACKGROUND: Treating vaso-occlusive painful crises in people with sickle cell
      disease is complex and requires multiple interventions. Extra fluids are
      routinely given as adjunct treatment, regardless of the individual's state of
      hydration with the aim of slowing or stopping the sickling process and thereby
      alleviating pain. OBJECTIVES: To determine the optimal route, quantity and type
      of fluid replacement for people with sickle cell disease with acute painful
      crises. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic
      Disorders Group Trials Register which comprises of references identified from
      comprehensive electronic database searches and handsearches of relevant journals
      and abstract books of conference proceedings. We also conducted searches of
      EMBASE, LILACS and the website www.ClinicalTrials.gov. Date of most recent search
      of the Group's Haemoglobinopathies Trials Register: February 2007. SELECTION
      CRITERIA: Randomised and quasi-randomised controlled trials that compared the
      administration of supplemental fluids adjunctive to analgesics by any route in
      people with any type of sickle cell disease during an acute painful episode,
      under medical supervision (inpatient, day care or community). DATA COLLECTION AND
      ANALYSIS: No relevant trials have yet been identified. MAIN RESULTS: Sixteen
      trials were identified by the initial search. Of these, 15 were not suitable for
      inclusion in this review and one study is awaiting further assessment. AUTHORS'
      CONCLUSIONS: Treating vaso-occlusive crises is complex and requires multiple
      interventions. Extra fluids, generally oral or intravenous, are routinely
      administered during acute painful episodes to people with sickle cell disease
      regardless of the individual's state of hydration. Reports of their use during
      these acute painful episodes do not state the efficacy of any single route, type
      or quantity of fluid compared to another. However, there are no randomized
      controlled trials that have assessed the safety and efficacy of different routes,
      types or quantities of fluid. This systematic review identifies the need for a
      multicentre randomized controlled trial assessing the efficacy and possible
      adverse effects of different routes, types and quantities of fluid administered
      to people with sickle cell disease during acute painful episodes.

PMID- 17443590
TI  - Electronic mosquito repellents for preventing mosquito bites and malaria
      infection.
AB  - BACKGROUND: Electronic mosquito repellents (EMRs) are marketed to prevent
      mosquitoes biting and to prevent malaria. OBJECTIVES: To assess whether EMRs
      prevent mosquito bites, and to assess any evidence of an effect on malaria
      infection. SEARCH STRATEGY: In August 2006, we searched the Cochrane Infectious
      Diseases Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, Cambridge
      Scientific Abstracts, and the Science Citation Index. We also checked conference
      proceedings, contacted international specialist centres and EMR manufacturers,
      and checked reference lists. SELECTION CRITERIA: Field entomological studies,
      which controlled for geographic site, time, and attractiveness of human
      participants, of EMRs for preventing mosquito bites; and randomized and quasi
      randomized controlled trials of EMRs to prevent malaria infection. DATA
      COLLECTION AND ANALYSIS: Two authors assessed trial quality, and extracted and
      analysed the data. MAIN RESULTS: Ten field entomological studies met the
      inclusion criteria. All 10 studies found that there was no difference in the
      number of mosquitoes caught from the bare body parts of the human participants
      with or without an EMR. No randomized or quasi-randomized controlled trials on
      the efficacy of EMR on malaria infection were found. AUTHORS' CONCLUSIONS: Field
      entomological studies confirm that EMRs have no effect on preventing mosquito
      bites. Therefore there is no justification for marketing them to prevent malaria
      infection.

PMID- 17443591
TI  - Chinese herbal medicines for hyperthyroidism.
AB  - BACKGROUND: Hyperthyroidism is a disease in which excessive amounts of thyroid
      hormones circulate in the blood. Patients, among other things suffer from
      tachycardia, warm moist skin and raised body temperature. The treatment of
      hyperthyroidism includes symptom relief and therapy with antithyroid medications,
      radioiodine and thyroidectomy. Medicinal herbs are used alone or in combination
      with antithyroid agents to treat hyperthyroidism in China and some other
      countries. OBJECTIVES: To assess the effects of Chinese herbal medicines for
      treating hyperthyroidism. SEARCH STRATEGY: Studies were obtained from
      computerised searches of MEDLINE, EMBASE, The Cochrane Library, the Chinese
      Biomedical Database. SELECTION CRITERIA: Randomised controlled trials comparing
      the effects of Chinese herbal medicines alone with Chinese herbal medicines
      combined with antithyroid drugs, radioiodine or both. DATA COLLECTION AND
      ANALYSIS: Three authors interviewed authors of all potentially relevant studies
      by telephone to verify randomisation procedures. One author entered data into a
      data extraction form and another author verified the results of this procedure.
      MAIN RESULTS: Thirteen relevant trials with 1770 participants were included. All
      of them were of low quality. Fifty-two studies still need to be assessed because
      the original authors could not be interviewed. None of these trials analysed
      mortality, health related quality of life, economic outcomes or compliance.
      Compared to antithyroid drugs alone the results showed that Chinese herbal
      medicines combined with antithyroid drugs may offer benefits in lowering relapse
      rates, reducing the incidence of adverse effects, relieving symptoms, improving
      thyroid antibody status and thyroid function. Two trials investigated Chinese
      herbal medicine versus radioiodine and reported improvements in anxiety,
      tachycardia and heat intolerance. However, thyroid function - with the exception
      of restored thyroid stimulating hormone (TSH) - was not significantly altered.
      AUTHORS' CONCLUSIONS: The results suggest that traditional Chinese herbal
      medicines added to other routine treatment have a therapeutic potential for
      people with hyperthyroidism. However, due to methodological limitations, we could
      not identify a well-designed trial to provide strong evidence for Chinese
      traditional herbal medicine in the treatment of hyperthyroidism. Thus, we
      currently cannot recommend any single preparation or formulation for clinical
      use.

PMID- 17443592
TI  - Prophylactic use of ergot alkaloids in the third stage of labour.
AB  - BACKGROUND: Previous research has shown that the prophylactic use of uterotonic
      agents in the third stage of labour reduces postpartum blood loss and moderate to
      severe postpartum haemorrhage. This is one of a series of systematic reviews
      assessing the effects of prophylactic use of uterotonic drugs - here,
      prophylactic ergot alkaloids compared with no uterotonic agents, and different
      regimens of administration of ergot alkaloids. OBJECTIVES: To determine the
      effectiveness and safety of prophylactic use of ergot alkaloids in the third
      stage of labour compared with no uterotonic agents, as well as with different
      routes or timing of administration for prevention of postpartum haemorrhage.
      SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (30 December 2006), the Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2006, Issue 4) and MEDLINE (1966 to December
      2006). SELECTION CRITERIA: All randomised or quasi-randomised controlled trials
      comparing prophylactic ergot alkaloids with no uterotonic agents or comparing
      different routes or timings of administration of ergot alkaloids in the third
      stage of labour among women giving birth vaginally. DATA COLLECTION AND ANALYSIS:
      We systematically reviewed the potential studies, considered eligible studies,
      assessed the validity of each included study and extracted data independently.
      MAIN RESULTS: We included six studies comparing ergot alkaloids with no
      uterotonic agents, with a total of 1996 women in ergot alkaloids group and 1945
      women in placebo or no treatment group. The use of injected ergot alkaloids in
      the third stage of labour significantly decreased mean blood loss (weighted mean
      difference -83.03 ml, 95% confidence interval (CI) -99.39 to -66.66 ml) and
      postpartum haemorrhage of at least 500 ml (relative risk (RR) 0.38, 95% CI 0.21
      to 0.69). The risk of retained placenta or manual removal of the placenta, or
      both, were inconsistent. Ergot alkaloids increased the risk of vomiting (RR
      11.81, 95% CI 1.78 to 78.28), elevation of blood pressure (RR 2.60, 95% CI 1.03
      to 6.57) and pain after birth requiring analgesia (RR 2.53, 95% CI 1.34 to 4.78).
      One study compared oral ergometrine with placebo and showed no significant
      benefit of ergometrine over placebo. No maternal adverse effects were reported.
      There were no included trials that compared different administration regimens of
      ergot alkaloids. AUTHORS' CONCLUSIONS: Prophylactic intramuscular or intravenous
      injections of ergot alkaloids are effective in reducing blood loss and postpartum
      haemorrhage, but adverse effects include vomiting, elevation of blood pressure
      and pain after birth requiring analgesia, particularly with the intravenous route
      of administration.

PMID- 17443593
TI  - Naftidrofuryl for acute stroke.
AB  - BACKGROUND: Stroke is the third most common cause of death and the most common
      cause of disability in the western world. The development of drugs to limit the
      effects of brain damage caused by stroke continues but no routine effective
      treatment has yet been identified. Naftidrofuryl has been reported to be
      beneficial in the treatment of acute stroke in some studies, but it is unclear
      whether all of the evidence supports these findings. OBJECTIVES: To assess the
      effects of naftidrofuryl in the acute phase of stroke. SEARCH STRATEGY: We
      searched the Cochrane Stroke Group Trials Register (last searched November 2006);
      the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane
      Database of Systematic Reviews, and the Database of Abstracts of Reviews of
      Effects (The Cochrane Library Issue 2, 2006); MEDLINE (1966 to July 2006); EMBASE
      (1980 to July 2006); Science Citation Index (1981 to July 2006); National
      Research Register (July 2006); LILACS Database (1982 to July 2006); metaRegister
      of Controlled Trials (mRCT) (July 2006); SUMsearch (July 2006). To identify
      further published, unpublished and ongoing studies we searched reference lists,
      handsearched conference proceedings and contacted pharmaceutical companies and
      authors of relevant articles. SELECTION CRITERIA: We included patients with acute
      ischaemic or haemorrhagic stroke clinically diagnosed by a medical practitioner
      with or without a computerised tomography (CT) scan. DATA COLLECTION AND
      ANALYSIS: Two authors independently selected trials for inclusion, assessed trial
      quality, and extracted data using data extraction forms or, if available, re
      analysed individual patient data. MAIN RESULTS: Six trials involving 1274
      participants were included. We found no significant benefits of naftidrofuryl
      compared with placebo in reducing the risks of mortality (pooled odds ratio (OR)
      1.03, 95% confidence interval (CI) 0.78 to 1.36, six studies) or combined death
      or dependency/disability (pooled OR 0.94, 95% CI 0.70 to 1.16, three studies).
      Pooled results showed naftidrofuryl had no significant effect on systolic,
      diastolic or mean arterial blood pressure. No trials reported the effects of
      naftidrofuryl on the risk of early death or deterioration, quality of life,
      stroke recurrence, or discharge site. However, we found a trend towards an
      increase in risk of minor adverse events in patients taking naftidrofuryl (OR
      1.99, 95% CI 0.96 to 4.11, P = 0.06). AUTHORS' CONCLUSIONS: There is not enough
      evidence to support the use of naftidrofuryl in the treatment of acute ischaemic
      or haemorrhagic stroke.

PMID- 17443594
TI  - Corticosteroids for treating nerve damage in leprosy.
AB  - BACKGROUND: Leprosy causes nerve damage which can result in nerve function
      impairment and disability. Corticosteroids are commonly used for treating nerve
      damage, although the long-term effect is uncertain. OBJECTIVES: To assess the
      effects of corticosteroids on nerve damage in leprosy. SEARCH STRATEGY: We
      searched the Cochrane Neuromuscular Disease Group Register, the Cochrane Central
      Register of Controlled Trials (Issue 4), MEDLINE (from 1966), EMBASE (from 1980),
      CINAHL (from 1980), LILACS (from 1982) in January 2006. 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
      corticosteroids 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 and cost
      effectiveness information from the trials and non-randomised studies. MAIN
      RESULTS: We included three randomised controlled trials involving 513 people. Two
      trials compared prednisolone with placebo. One trial treated mild sensory
      impairment of less than six months duration and the other trial treated nerve
      function impairment of 6 to 24 months duration. Both trials examined an effect
      twelve months from the start of treatment. There was no significant difference in
      nerve function improvement between people treated with prednisolone or with
      placebo. The third trial compared three corticosteroid regimens for severe type 1
      reactions. This trial did not report the prespecified outcomes. However, after 12
      months, a significantly higher proportion of individuals on a 3-month course of
      prednisolone required extra corticosteroids compared to the groups with a high
      dose and low-dose regimen of five months duration. Diabetes and peptic or
      infected ulcer were sometimes reported as serious adverse events in the placebo
      controlled trials, but not significantly more often in the corticosteroid than
      placebo groups. AUTHORS' CONCLUSIONS: Corticosteroids are used for treating acute
      nerve damage in leprosy, but evidence from randomised controlled trials does not
      show a significant long-term effect. Randomised controlled trials are needed to
      establish their effectiveness, the optimal regimens and to examine new therapies.

PMID- 17443595
TI  - Early developmental intervention programs post hospital discharge to prevent
      motor and cognitive impairments in preterm infants.
AB  - BACKGROUND: Infants born preterm are at increased risk of developing cognitive
      and motor impairments compared with infants born at term. Early developmental
      interventions have been used in the clinical setting with the aim of improving
      the overall functional outcome for these infants. However, the benefit of these
      programs remains unclear. OBJECTIVES: To review the effectiveness of early
      developmental intervention post-discharge from hospital for preterm (< 37 weeks)
      infants on motor or cognitive development. SEARCH STRATEGY: The Cochrane Neonatal
      Review group search strategy was used to identify randomised and quasi-randomised
      controlled trials of early developmental interventions post hospital discharge.
      Two review authors independently searched the Cochrane Central Register of
      Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE Advanced, CINAHL,
      PsychINFO and EMBASE (1966 through February 2006). SELECTION CRITERIA: Studies
      included had to be randomised or quasi-randomised controlled trials of early
      developmental intervention programs that commenced within the first 12 months of
      life for infants born at < 37 weeks with no major congenital abnormalities.
      Intervention could commence as an inpatient; however, a post discharge component
      was necessary to be included in this review. The outcome measures were not pre
      specified other than that they had to assess cognitive and/or motor ability. The
      rates of intellectual impairment, cerebral palsy and development co-ordination
      disorder were also documented. DATA COLLECTION AND ANALYSIS: Data were extracted
      and entered by two independent review authors. Cognitive and motor outcomes were
      pooled in three age groups - infant (0 to 2 years), preschool (3 to < 5 years) or
      school age (5 to 17 years). Meta-analysis was carried out using RevMan 4.2 to
      determine the effects of early developmental intervention in the short (0 to 2
      years), medium (3 to < 5 years) and long term (5 to 17 years). Subgroup analysis
      was carried out in relation to; gestational age, birthweight, brain injury,
      commencement of intervention, focus of intervention and study quality. MAIN
      RESULTS: Sixteen studies met the inclusion criteria (2379 randomised patients).
      Six of these studies were RCTs and had strong methodological quality. There was
      variability with regard to the focus and intensity of the intervention, and in
      length of follow-up. Meta-analysis concluded that intervention improved cognitive
      outcomes at infant age (developmental quotient [DQ]: standard mean difference
      [SMD] 0.46 SD; 95% CI 0.36 0.57; P < 0.0001), and at preschool age (intelligence
      quotient [IQ]; SMD 0.46 SD; 95%CI 0.33, 0.59; P < 0.0001). However, this effect
      was not sustained at school age (IQ; SMD 0.02 SD; 95% CI -0.10, 0.14; P = 0.71).
      There was significant heterogeneity between studies for cognitive outcomes at
      infant and school ages. There was little evidence of an effect of early
      intervention on motor outcomes in the short, medium or long-term, but there were
      only two studies reporting outcomes beyond 2 years. AUTHORS' CONCLUSIONS: Early
      intervention programs for preterm infants have a positive influence on cognitive
      outcomes in the short to medium term. However, there was significant
      heterogeneity between the interventions included in this review. Further research
      is needed to determine which early developmental interventions are the most
      effective at improving cognitive and motor outcomes, and on the longer-term
      effects of these programs. Cost-effectiveness and access to services should also
      be evaluated since they are important factors when considering implementation of
      an early developmental intervention program for a preterm infant.

PMID- 17443596
TI  - Advance provision of emergency contraception for pregnancy prevention (full
      review).
AB  - BACKGROUND: Emergency contraception can prevent pregnancy when taken after
      unprotected intercourse. Obtaining emergency contraception within the recommended
      time frame is difficult for many women. Advance provision, in which women receive
      a supply of emergency contraception before unprotected sex, could circumvent some
      obstacles to timely use. OBJECTIVES: To summarize randomized controlled trials
      evaluating advance provision of emergency contraception to explore effects on
      pregnancy rates, sexually transmitted infections, and sexual and contraceptive
      behaviors. SEARCH STRATEGY: In August 2006, we searched CENTRAL, EMBASE, POPLINE,
      MEDLINE via PubMed, and a specialized emergency contraception article database.
      We also searched reference lists and contacted experts to identify additional
      published or unpublished trials. SELECTION CRITERIA: We included randomized
      controlled trials comparing advance provision and standard access, which was
      defined as any of the following: counseling which may or may not have included
      information about emergency contraception, or provision of emergency
      contraception on request at a clinic or pharmacy. DATA COLLECTION AND ANALYSIS:
      We evaluated all identified titles and abstracts found for potential inclusion.
      Two reviewers independently abstracted data and assessed study quality. We
      entered and analyzed data using RevMan 4.2.8. We calculated odds ratios with 95%
      confidence intervals for dichotomous data and weighted mean differences with 95%
      confidence intervals for continuous data. MAIN RESULTS: Eight randomized
      controlled trials met our criteria for inclusion, representing 6389 patients in
      the United States, China and India. Advance provision did not decrease pregnancy
      rates (OR 1.0; 95% CI: 0.78 to 1.29 in studies for which we included twelve month
      follow-up data; OR 0.91; 95% CI: 0.69 to 1.19 in studies for which we included
      six month follow-up data; OR 0.49; 95% CI: 0.09 to 2.74 in a study with three
      month follow up data), despite increased use (single use: OR 2.52; 95% CI 1.72 to
      3.70; multiple use: OR 4.13; 95% CI 1.77 to 9.63) and faster use (weighted mean
      difference (WMD) -14.6 hours; 95% CI -16.77 to -12.4 hours). Advance provision
      did not lead to increased rates of sexually transmitted infections (OR 0.99; 95%
      CI 0.73 to 1.34), increased frequency of unprotected intercourse, nor changes in
      contraceptive methods. Women who received emergency contraception in advance were
      equally as likely to use condoms as other women. AUTHORS' CONCLUSIONS: Advance
      provision of emergency contraception did not reduce pregnancy rates when compared
      to conventional provision. Advance provision does not negatively impact sexual
      and reproductive health behaviors and outcomes. Women should have easy access to
      emergency contraception, because it can decrease the chance of pregnancy.
      However, the interventions tested thus far have not reduced overall pregnancy
      rates in the populations studied.

PMID- 17443597
TI  - Orthodontic and orthopaedic treatment for anterior open bite in children.
AB  - BACKGROUND: Anterior open bite occurs when there is a lack of vertical overlap of
      the upper and lower incisors. The aetiology is multifactorial including: oral
      habits, unfavourable growth patterns, enlarged lymphatic tissue with mouth
      breathing. Several treatments have been proposed to correct this malocclusion,
      but interventions are not supported by strong scientific evidence. OBJECTIVES:
      The aim of this systematic review was to evaluate orthodontic and orthopaedic
      treatments to correct anterior open bite in children. SEARCH STRATEGY: Search
      strategies were developed for MEDLINE and revised appropriately for the following
      databases: Cochrane Oral Health Group Trials Register; CENTRAL (The Cochrane
      Library 2005, Issue 4); PubMed (1966 to December 2005); EMBASE (1980 to February
      2006); Lilacs (1982 to December 2005); Brazilian Bibliography of Odontology (BBO)
      (1986 to December 2005); and SciELO (1997 to December 2005). Chinese journals
      were handsearched and the bibliographies of papers were retrieved. SELECTION
      CRITERIA: All randomised or quasi-randomised controlled trials of orthodontic or
      orthopaedic treatments or both to correct anterior open bite in children. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed the
      eligibility of all reports identified. Risk ratios (RRs) and corresponding 95%
      confidence intervals (CIs) were calculated for dichotomous data. The continuous
      data were expressed as described by the author. MAIN RESULTS: Twenty-eight trials
      were potentially eligible, but only three randomised controlled trials were
      included comparing: effects of Frankel's function regulator-4 (FR-4) with lip
      seal training versus no treatment; repelling-magnet splints versus bite-blocks;
      and palatal crib associated with high-pull chincup versus no treatment. The study
      comparing repelling-magnet splints versus bite-blocks could not be analysed
      because the authors interrupted the treatment earlier than planned due to side
      effects in four of ten patients.FR-4 associated with lip-seal training (RR = 0.02
      (95% CI 0.00 to 0.38)) and removable palatal crib associated with high-pull
      chincup (RR = 0.23 (95% CI 0.11 to 0.48)) were able to correct anterior open
      bite.No study described: randomisation process, sample size calculation, there
      was not blinding in the cephalometric analysis and the two studies evaluated two
      interventions at the same time. These results should be therefore viewed with
      caution. AUTHORS' CONCLUSIONS: :There is weak evidence that the interventions FR
      4 with lip-seal training and palatal crib associated with high-pull chincup are
      able to correct anterior open bite. Given that the trials included have potential
      bias, these results must be viewed with caution. Recommendations for clinical
      practice cannot be made based only on the results of these trials. More
      randomised controlled trials are needed to elucidate the interventions for
      treating anterior open bite.

PMID- 17443598
TI  - Oral appliances and functional orthopaedic appliances for obstructive sleep
      apnoea in children.
AB  - BACKGROUND: Apnoea is a breathing disorder marked by the absence of airflow at
      the nose or mouth. In children, risk factors include adenotonsillar hypertrophy,
      obesity, neuromuscular disorders and craniofacial anomalies. The most common
      treatment for obstructive sleep apnoea syndrome (OSAS) in childhood is
      adenotonsillectomy. This approach is limited by its surgical risks, mostly in
      children with comorbities and, in some patients, by recurrence that can be
      associated with craniofacial problems. Oral appliances and functional orthopaedic
      appliances have been used for patients who have OSAS and craniofacial anomalies
      because they change the mandible posture forwards and potentially enlarge the
      upper airway and increase the upper airspace, improving the respiratory function.
      OBJECTIVES: To assess the effectiveness of oral appliances or functional
      orthopaedic appliances for OSAS in children. SEARCH STRATEGY: A sensitive search
      was developed for the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library 2005, Issue 3); PubMed (January 1966 to September 2005);
      EMBASE (1980 to September 2005); Lilacs (1982 to September 2005); BBO
      Bibliografia Brasileira de Odontologia (1986 to September 2005); and SciELO (1997
      to September 2005). There was no restriction of language or source of
      information. SELECTION CRITERIA: All randomised or quasi-randomised controlled
      trials comparing all types of oral and functional orthopaedic appliances with
      placebo or no treatment, in children 15 years old or younger. PRIMARY OUTCOME:
      reduction of apnoea to less than one episode per hour. SECONDARY OUTCOMES: dental
      and skeletal relationship, sleep parameters improvement, cognitive and
      phonoaudiologic function, behavioural problems, drop outs and withdrawals,
      quality of life, side effects (tolerability), economic evaluation. DATA
      COLLECTION AND ANALYSIS: Data were independently extracted by two review authors.
      Authors were contacted for additional information. Risk ratios with 95%
      confidence intervals were calculated for all important dichotomous outcomes. MAIN
      RESULTS: The initial search identified 384 trials. One of them, reporting results
      from a total of 23 patients, was suitable for inclusion in the review. Data
      provided in the published report did not answer all the questions from this
      review, but some of them were, and the presented results favour treatment.
      AUTHORS' CONCLUSIONS: At present there is no sufficient evidence to state that
      oral appliances or functional orthopaedic appliances are effective in the
      treatment of OSAS in children. Oral appliances or functional orthopaedic
      appliances may be helpful in the treatment of children with craniofacial
      anomalies which are risk factors for apnoea.

PMID- 17443599
TI  - Antenatal phenobarbital for reducing neonatal jaundice after red cell
      isoimmunization.
AB  - BACKGROUND: Neonates from isoimmunized pregnancies have increased morbidity from
      neonatal jaundice. The increased bilirubin from haemolysis often needs
      phototherapy, exchange transfusion or both after birth. Various trials in
      pregnant women who were not isoimmunized but had other risk factors for neonatal
      jaundice have shown a reduction in need for phototherapy and exchange transfusion
      by the use of antenatal phenobarbital. A recent retrospective case-controlled
      study showed reduction in the need for exchange transfusion for the neonates from
      isoimmunized pregnancies. OBJECTIVES: To assess the effects of antenatal
      phenobarbital in red cell isoimmunized pregnancies in reducing the incidence of
      phototherapy and exchange transfusion for the neonate. SEARCH STRATEGY: We
      searched the Cochrane Pregnancy and Childbirth Group's Trials Register (June
      2006). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of
      pregnant women established to have red cell isoimmunization in the current
      pregnancy during their antenatal testing and given phenobarbital alone or in
      combination with other drugs before birth. DATA COLLECTION AND ANALYSIS: All
      three review authors independently assessed study eligibility and quality. MAIN
      RESULTS: No trials met the inclusion criteria for this review. AUTHORS'
      CONCLUSIONS: The use of antenatal phenobarbital to reduce neonatal jaundice in
      red cell isoimmunized pregnant women has not been evaluated in randomised
      controlled trials.

PMID- 17443600
TI  - Interventions for preventing delirium in hospitalised patients.
AB  - BACKGROUND: Delirium is a common mental disorder with serious adverse outcomes in
      hospitalised patients. It is associated with increases in mortality, physical
      morbidity, length of hospital stay, institutionalisation and costs to healthcare
      providers. A range of risk factors has been implicated in its aetiology,
      including aspects of the routine care and environment in hospitals. Prevention of
      delirium is clearly desirable from patients' and carers' perspectives, and to
      reduce hospital costs. Yet it is currently unclear whether interventions for
      prevention of delirium are effective, whether they can be successfully delivered
      in all environments, and whether different interventions are necessary for
      different groups of patients. OBJECTIVES: Our primary objective was to determine
      the effectiveness of interventions designed to prevent delirium in hospitalised
      patients. We also aimed to highlight the quality and quantity of research
      evidence to prevent delirium in these settings. SEARCH STRATEGY: We searched the
      Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on
      28th September, 2005. As the searches in MEDLINE, EMBASE, CINAHL and PsycINFO for
      the Specialized Register would not necessarily have picked up all delirium
      prevention trials, these databases were searched again on 28th October, 2005. We
      also examined reference lists of retrieved articles, reviews and books. Experts
      in this field were contacted and the Internet searched for further references and
      to locate unpublished trials. SELECTION CRITERIA: Randomised controlled trials
      evaluating any interventions to prevent delirium in hospitalised patients. DATA
      COLLECTION AND ANALYSIS: Data collection and quality assessment were performed by
      three reviewers independently and agreement reached by consensus. MAIN RESULTS:
      Six studies with a total of 833 participants were identified for inclusion. All
      were conducted in surgical settings, five in orthopaedic surgery and one in
      patients undergoing resection for gastric or colon cancer. Only one study of 126
      hip fracture patients comparing proactive geriatric consultation with usual care
      was sufficiently powered to detect a difference in the primary outcome, incident
      delirium. Total cumulative delirium incidence during admission was reduced in the
      intervention group (OR 0.48 [95% CI 0.23, 0.98]; RR 0.64 [95% CI 0.37, 0.98]),
      suggesting a 'number needed to treat' of 5.6 patients to prevent one case. The
      intervention was particularly effective in preventing severe delirium. In
      logistic regression analyses adjusting for pre fracture dementia and Activities
      of Daily Living impairment, there was no reduction in effect size, OR 0.6, but
      this no longer remained significant [95% CI 0.3,1.3]. There was no effect on the
      duration of delirium episodes, length of hospital stay, and cognitive status or
      institutionalisation at discharge. There was also no significant difference in
      cumulative delirium incidence between treatment and control groups in a sub-group
      of 50 patients with dementia (RR 0.9 [95% CI 0.59, 1.36]). In another trial of
      low dose haloperidol prophylaxis, there was no difference in delirium incidence
      but the severity and duration of a delirium episode, and length of hospital stay
      were all reduced. We identified no completed studies in hospitalised medical,
      care of the elderly, general surgery, cancer or intensive care patients. In
      outcomes, no studies examined for death, use of psychotropic medication,
      activities of daily living, psychological morbidity, quality of life, carers or
      staff psychological morbidity, cost of intervention and cost to health care
      services. Outcomes were only reported up to discharge, with no studies reporting
      medium or longer-term effects. AUTHORS' CONCLUSIONS: Research evidence on
      effectiveness of interventions to prevent delirium is sparse. Based on a single
      study, a programme of proactive geriatric consultation may reduce delirium
      incidence and severity in patients undergoing surgery for hip fracture.
      Prophylactic low dose haloperidol may reduce severity and duration of delirium
      episodes and shorten length of hospital admission in hip surgery. Further studies
      of delirium prevention are needed.

PMID- 17443601
TI  - Epinephrine injection versus epinephrine injection and a second endoscopic method
      in high risk bleeding ulcers.
AB  - BACKGROUND: Endoscopic therapy reduces rebleeding rate, need for surgery, and
      mortality in patients with bleeding peptic ulcers. Injection of epinephrine is
      the most popular therapeutic method. Guidelines disagree on the need for a second
      haemostatic procedure immediately after epinephrine. OBJECTIVES: The objective of
      this review was to determine whether the addition of a second procedure improves
      efficacy or patient outcomes or both after epinephrine injection in adults with
      high risk bleeding ulcers. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials - CENTRAL (which includes the Cochrane Upper
      Gastrointestinal and Pancreatic Diseases Group Trials Register) (The Cochrane
      Library Issue 1, 2006), MEDLINE (1966 to February 2006), EMBASE (1980 to February
      2006) and reference lists of articles. We also contacted experts in the field.
      SELECTION CRITERIA: Randomised studies comparing endoscopic treatment:
      epinephrine alone versus epinephrine associated with a second haemostatic method
      in adults with haemorrhage from peptic ulcer disease with major stigmata of
      bleeding as defined by the Forrest classification. Bleeding must have been
      confirmed by endoscopy. DATA COLLECTION AND ANALYSIS: Two authors independently
      assessed trial quality and extracted data. MAIN RESULTS: Seventeen studies
      including 1763 people were included. Adding a second procedure reduced further
      bleeding rate from 18.8% to 10.4%; Peto Odds Ratio 0.51; 95% confidence interval
      (CI) 0.39 to 0.66, and emergency surgery from 10.8% to 7.1%; OR 0.63; 95% CI 0.45
      to 0.89. Mortality fell from 5% to 2.5% OR 0.50; 95% CI 0.30 to 0.82. Subanalysis
      showed that the risk of further bleeding decreased regardless of which second
      procedure was applied. In addition, the risk was reduced in all subgroups.
      AUTHORS' CONCLUSIONS: Additional endoscopic treatment after epinephrine injection
      reduces further bleeding, the need for surgery and mortality in patients with
      bleeding peptic ulcer.

PMID- 17443602
TI  - Antipsychotics for delirium.
AB  - BACKGROUND: Delirium occurs in up to 30% of hospitalised patients and is
      associated with prolonged hospital stay and increased morbidity and mortality.
      Recently published reports have suggested that the standard drug for delirium,
      haloperidol, a typical antipsychotic that may cause adverse extrapyramidal
      symptoms among patients, may be replaced by atypical antipsychotics such as
      risperidone, olanzapine or quetiapine, that are as effective as haloperidol in
      controlling delirium, but that have a lower incidence of extrapyramidal adverse
      effects. OBJECTIVES: To compare the efficacy and incidence of adverse effects of
      haloperidol with risperidone, olanzapine, and quetiapine in the treatment of
      delirium. SEARCH STRATEGY: The trials were identified from a search of the
      Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on
      7 August 2006 using the search terms:haloperidol or haldol or risperidone or
      risperdal* or quetiapine or seroquel* or olanzapine or zyprexa* or aminotriazole
      or sertindole or leponex* or zeldox* or ziprasidone. SELECTION CRITERIA: Types of
      studies included unconfounded, randomised trials with concealed allocation of
      subjects. For inclusion trials had to have assessed patients pre- and post
      treatment. Where cross-over studies are included, only data from the first part
      of the study were examined. Interrupted time series were excluded. Length of
      trial and number of measurements did not influence the selection of trials for
      study. Where indicated, individual patient data were requested for further
      examination. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data from
      included trials. Data were pooled where possible, and analysed using appropriate
      statistical methods. Odds ratios of average differences were calculated. Only
      'intention to treat' data were included. Analysis included haloperidol treated
      patients, compared with placebo. MAIN RESULTS: Three studies were found that
      satisfied selection criteria. These studies compared haloperidol with
      risperidone, olanzapine, and placebo in the management of delirium and in the
      incidence of adverse drug reactions. Decrease in delirium scores were not
      significantly different comparing the effect of low dose haloperidol (< 3.0 mg
      per day) with the atypical antipsychotics olanzapine and risperidone (Odds ratio
      0.63 (95% CI 10.29 - 1.38; p = 0.25). Low dose haloperidol did not have a higher
      incidence of adverse effects than the atypical antipsychotics. High dose
      haloperidol (> 4.5 mg per day) in one study was associated with an increased
      incidence of extrapyramidal adverse effects, compared with olanzapine. Low dose
      haloperidol decreased the severity and duration of delirium in post-operative
      patients, although not the incidence of delirium, compared to placebo controls in
      one study. There were no controlled trials comparing quetiapine with haloperidol.
      AUTHORS' CONCLUSIONS: There is no evidence that haloperidol in low dosage has
      different efficacy in comparison with the atypical antipsychotics olanzapine and
      risperidone in the management of delirium or has a greater frequency of adverse
      drug effects than these drugs. High dose haloperidol was associated with a
      greater incidence of side effects, mainly parkinsonism, than the atypical
      antipsychotics. Low dose haloperidol may be effective in decreasing the degree
      and duration of delirium in post-operative patients, compared with placebo. These
      conclusions must be tempered by the observation that they are based on small
      studies of limited scope, and therefore will require further corroborating
      evidence before they can be translated into specific recommendation for the
      treatment of delirium.

PMID- 17443603
TI  - Topical cystic fibrosis transmembrane conductance regulator gene replacement for
      cystic fibrosis-related lung disease.
AB  - BACKGROUND: Cystic fibrosis is caused by a defective gene encoding a protein
      called the cystic fibrosis transmembrane conductance regulator (CFTR), and is
      characterised by chronic lung infection resulting in inflammation and progressive
      lung damage that results in a reduced life expectancy. OBJECTIVES: To determine
      whether topical CFTR gene replacement therapy to the lungs in people with cystic
      fibrosis is associated with improvements in clinical outcomes, and to assess any
      adverse effects. 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. Date of most recent search: February
      2007 SELECTION CRITERIA: Randomised controlled trials comparing topical CFTR gene
      delivery to the lung, using either viral or non-viral delivery systems, with
      placebo or an alternative delivery system in people with confirmed cystic
      fibrosis. DATA COLLECTION AND ANALYSIS: The authors independently extracted data
      and assessed study quality. Authors of included studies were contacted and asked
      for any available additional data. Meta-analysis was limited due to differing
      study designs. MAIN RESULTS: Three randomised controlled trials met the inclusion
      criteria for this review, involving a total of 155 participants. Thirteen studies
      were excluded. The included studies differed in terms of CFTR gene replacement
      agent and study design, which limited the meta-analysis. Although the first Moss
      study reported a significant improvement in respiratory function (FEV(1)) 30 days
      after participants had received their first dose of gene therapy agent, this
      finding was not confirmed in their larger second study or in our meta-analysis.In
      participants who received the CFTR gene transfer agents in the Alton study,
      "influenza-like" symptoms were found (relative risk 7.00 (95% confidence interval
      (CI) 1.10 to 44.61)). There were no other significant increases in adverse events
      in any of the studies. Alton measured ion transport in the lower airways and
      demonstrated significant changes toward normal values in the participants who
      received gene transfer agents (P < 0.0001), weighted mean difference 6.86 (95% CI
      of 3.77 to 9.95). In these participants there was also evidence of increased salt
      transport in cells obtained by brushing the lower airway. These outcomes, whilst
      important, are not of direct clinical relevance. AUTHORS' CONCLUSIONS: There is
      currently no evidence to support the use of CFTR gene transfer reagents as a
      treatment for lung disease in people with cystic fibrosis. Future studies need to
      investigate clinically important outcome measures.

PMID- 17443604
TI  - Tailored interventions based on sputum eosinophils versus clinical symptoms for
      asthma in children and adults.
AB  - BACKGROUND: Asthma severity and control can be measured both subjectively and
      objectively. Sputum analysis for evaluation of percentage of sputum eosinophilia
      directly measures airway inflammation, and is one method of objectively
      monitoring asthma. Interventions for asthma therapies have been traditionally
      based on symptoms and spirometry. OBJECTIVES: To evaluate the efficacy of
      tailoring asthma interventions based on sputum analysis in comparison to clinical
      symptoms (with or without spirometry/peak flow) for asthma related outcomes in
      children and adults. SEARCH STRATEGY: We searched the Cochrane Airways Group
      Specialised Register of Trials, the Cochrane Central Register of Controlled
      Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles. The last
      search was on 31 October 2006. SELECTION CRITERIA: All randomised controlled
      comparisons of adjustment of asthma therapy based on sputum eosinophils compared
      to traditional methods (primarily clinical symptoms and spirometry/peak flow).
      DATA COLLECTION AND ANALYSIS: Results of searches were reviewed against pre
      determined criteria for inclusion. Three sets of reviewers selected relevant
      studies. Two review authors independently assessed trial quality extracted data.
      Authors were contacted for further information but none were received. Data was
      analysed as "treatment received" and sensitivity analyses performed. MAIN
      RESULTS: Three adult studies were included; these studies were clinically and
      methodologically heterogenous (use of medications, cut off for percentage of
      sputum eosinophils and definition of asthma exacerbation). There were no eligible
      paediatric studies. Of 246 participants randomised, 221 completed the trials. In
      the meta-analysis, a significant reduction in number of participants who had one
      or more asthma exacerbations occurred when treatment was based on sputum
      eosinophils in comparison to clinical symptoms; pooled odds ratio (OR) was 0.49
      (95% CI 0.28 to 0.87); number needed to treat to benefit (NNTB) was 6 (95% CI 4
      to 32). There were also differences between groups in the rate of exacerbation
      (any exacerbation per year) and severity of exacerbations defined by requirement
      for use of oral corticosteroids but the reduction in hospitalisations was not
      statistically significant. Data for clinical symptoms, quality of life and
      spirometry were not significantly different between groups. The mean dose of
      inhaled corticosteroids per day was similar in both groups and no adverse events
      were reported. However sputum induction was not always possible. AUTHORS'
      CONCLUSIONS: Tailored asthma interventions based on sputum eosinophils is
      beneficial in reducing the frequency of asthma exacerbations in adults with
      asthma. This review supports the use of sputum eosinophils to tailor asthma
      therapy for adults with frequent exacerbations and severe asthma. Further studies
      need to be undertaken to strengthen these results and no conclusion can be drawn
      for children with asthma.

PMID- 17443606
TI  - Interventions for squamous cell carcinoma of the conjunctiva in HIV-infected
      individuals.
AB  - BACKGROUND: Squamous cell carcinoma of the conjunctiva is a rare, slow-growing
      tumour of the eye, normally affecting elderly men around 70 years of age. In
      Africa, however, the disease is different. The incidence is rising rapidly,
      affecting young persons (around 35 years off age), and usually affecting women.
      It is more aggressive, with a mean history of three months at presentation. This
      pattern is related to the co-existence of the HIV/AIDS pandemic, high HPV
      exposure, and solar radiation in the region. Various interventions exist, but
      despite therapy, there is a high recurrence rate (up to 43%) and poor cosmetic
      results in late disease. This review was conducted to evaluate the interventions
      for treatment of conjunctival squamous cell carcinoma in HIV-infected
      individuals. OBJECTIVES: To evaluate the effect of interventions for treating
      squamous cell carcinoma of the conjunctiva in HIV-infected individuals on local
      control, recurrence, death, time to recurrence, and adverse events. SEARCH
      STRATEGY: Using a sensitive search strategy, we attempted to identify all
      relevant trials, regardless of language or publication status, from the following
      electronic databases; Medline/PubMed, CENTRAL, AIDSearch, EMBASE, LILACS, African
      Healthline, Cochrane HIV/AIDS Specialised Register, and the Cochrane Cancer
      Network Specialised Register. We searched the clinical trial register of the US
      National Institutes of Health, searched the international conference proceedings
      of AIDS and AIDS-related cancers, and contacted individual researchers, research
      organisations, and pharmaceutical companies that manufacture the drugs used as
      interventions. Searches were done between September 2005 and June 2006. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) involving HIV-infected individuals
      with ocular surface squamous neoplasia. 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 interventions
      currently used against conjunctival squamous cell carcinoma in HIV-infected
      individuals were identified. AUTHORS' CONCLUSIONS:  IMPLICATIONS FOR PRACTICE:
      Current clinical practice in treatment of squamous cell carcinoma of the
      conjunctiva rests on a weak evidence base of case series and case reports.
      IMPLICATIONS FOR RESEARCH: Randomised controlled trials for treatment of this
      disease are needed in settings where it occurs most frequently. Preventive
      interventions also need to be identified. HIV/AIDS research has not focused on
      treatment of this tumour.

PMID- 17443605
TI  - Long-acting insulin analogues versus NPH insulin (human isophane insulin) for
      type 2 diabetes mellitus.
AB  - BACKGROUND: Despite indications from epidemiological trials that higher blood
      glucose concentrations are associated with a higher risk for developing micro-
      and macrovascular complications, evidence for a beneficial effect of
      antihyperglycaemic therapy in patients with type 2 diabetes mellitus is
      conflicting. Two large studies, the United Kingdom Prospective Diabetes Study
      (UKPDS) and the University Group Diabetes Program (UGDP), did not find a
      reduction of cardiovascular endpoints through improvement of metabolic control.
      The theoretical benefits of newer insulin analogues might result in fewer
      macrovascular and microvascular events. OBJECTIVES: To assess the effects of long
      term treatment with long-acting insulin analogues (insulin glargine and insulin
      detemir) compared to NPH insulin in patients with type 2 diabetes mellitus.
      SEARCH STRATEGY: Studies were obtained from computerised searches of MEDLINE,
      EMBASE, The Cochrane Library and communication with experts in the field as well
      as insulin producing companies. SELECTION CRITERIA: Studies were included if they
      were randomised controlled trials in adults with diabetes mellitus type 2 and had
      a trial duration of at least 24 weeks. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial quality and extracted data. Pooling of studies by
      means of random-effects meta-analyses was performed. MAIN RESULTS: Six studies
      comparing insulin glargine to NPH (Neutral Protamine Hagedorn) insulin and two
      studies comparing insulin detemir to NPH insulin were identified. In these
      trials, 1715 patients were randomised to insulin glargine and 578 patients to
      insulin detemir. Duration of the included trials ranged from 24 to 52 weeks.
      Metabolic control, measured by glycosylated haemoglobin A1c (HbA1c) as a
      surrogate endpoint, and adverse effects did not differ in a clinical relevant way
      between treatment groups. While no statistically significant difference for
      severe hypoglycaemia rates was shown in any of the trials, the rate of
      symptomatic, overall and nocturnal hypoglycaemia was statistically significantly
      lower in patients treated with either insulin glargine or detemir. No evidence
      for a beneficial effect of long-acting analogues on patient-oriented outcomes
      like mortality, morbidity, quality of life or costs could be obtained. AUTHORS'
      CONCLUSIONS: Our analysis suggests, if at all only a minor clinical benefit of
      treatment with long-acting insulin analogues for patients with diabetes mellitus
      type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic
      events. Until long-term efficacy and safety data are available, we suggest a
      cautious approach to therapy with insulin glargine or detemir.

PMID- 17443607
TI  - Interventions for the treatment of decreased bone mineral density associated with
      HIV infection.
AB  - BACKGROUND: Decreased bone mineral density (BMD) occurs more commonly in patients
      with HIV than in the general population, making this group more susceptible to
      fragility fractures. However, bone loss is under-treated in patients with HIV.
      OBJECTIVES: To assess the effects of interventions aimed at increasing bone
      mineral density in HIV-infected adults. SEARCH STRATEGY: We searched MEDLINE,
      EMBASE, LILACS, The Cochrane Library, Meeting Abstracts, AIDSTRIALS, ACTIS,
      Current Controlled Trials, National Institutes of Health Clinical Trials
      Registry, and CenterWatch (search date July 2006). SELECTION CRITERIA: Randomised
      trials comparing any pharmacological or non-pharmacological therapy with placebo,
      no treatment, or an alternative therapy, with the goal of increasing bone mineral
      density in adult (age 18 years or over) patients with HIV. DATA COLLECTION AND
      ANALYSIS: Two reviewers independently assessed trial eligibility and quality, and
      extracted data. Where data were incomplete or unclear, conflicts were resolved
      with discussion and/or trial authors were contacted for further details. MAIN
      RESULTS: Three completed randomised-controlled studies examined the role of
      alendronate in patients with HIV and osteopenia or osteoporosis. When all three
      studies were combined, much heterogeneity was seen (p<0.0001), most likely due to
      different populations and interventions. A sensitivity analysis showed that in
      two studies without heterogeneity (p=0.11), alendronate, calcium and vitamin D
      improved lumbar BMD after one year when compared with calcium and vitamin D
      (weighted mean difference +2.65 95% confidence interval (CI) 0.80, 4.51 percent).
      However the alendronate group did not have less fragility fractures, relative
      risk (RR) 1.28 (95% CI 0.20, 8.21), or osteoporosis, RR 0.50 (95% CI 0.24, 1.01).
      Adverse events were not significantly different between groups, RR 1.28 (95%
      0.20, 8.21). One randomised-controlled study done in patients with AIDS wasting
      found that after three months, testosterone enanthane improved lumbar BMD
      compared to placebo by +3.70 (95% CI 0.48, 6.92) percent, but progressive
      resistance training did not improve lumbar BMD (+0.40 95% CI -2.81, 3.61
      percent). No group in this study had any adverse effects. AUTHORS' CONCLUSIONS:
      The very limited data reviewed showed that bisphosphonate therapy andin those
      with AIDS wasting syndrome, testosteronemay be safe and possibly effective
      methods to improve bone mineral density in HIV patients. The available studies
      are small, of short duration, and not powered to detect changes in WHO categories
      and fracture rates. Larger studies using bisphosphonates are currently underway.
      The role of colecalciferol, androgen replacement in women, and growth hormone are
      also under investigation.

PMID- 17443608
TI  - Cotrimoxazole for prophylaxis or treatment of opportunistic infections of
      HIV/AIDS in patients with previous history of hypersensitivity to cotrimoxazole.
AB  - BACKGROUND: Opportunistic infections continue to cause a significant amount of
      morbidity and mortality worldwide in patients infected with HIV. Trimethoprim
      sulfamethoxazole (cotrimoxazole) is used in the treatment and prophylaxis of
      several opportunistic infections. In patients with HIV/AIDS, cotrimoxazole use
      can cause a higher rate of adverse drug reactions than in the general population.
      Given the cost-effectiveness of cotrimoxazole, the management of these adverse
      reactions has included continuing the drug (treating-through) and reintroducing
      the drug at a later date, either using dose-escalation (desensitization), or
      rechallenge at full dose. This systematic review is the first to examine the
      differences in patient outcomes between these strategies. OBJECTIVES: To compare
      the rate of discontinuation of cotrimoxazole and adverse reactions among the
      three strategies of treating-through, desensitization, and rechallenge in
      patients living with HIV who previously had an adverse reaction to cotrimoxazole.
      SEARCH STRATEGY: We searched MEDLINE, EMBASE, LILACS, The Cochrane Library,
      Meeting Abstracts, AIDSTRIALS, ACTIS, Current Controlled Trials, The National
      Institutes of Health Clinical Trials Registry, and CenterWatch (search date May
      2006). SELECTION CRITERIA: Randomised trials comparing treating-through,
      rechallenge, or desensitization of cotrimoxazole treatment or prophylaxis in
      adults (age 18 years or over) and/or children (age 17 years or under). DATA
      COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility
      and quality, and extracted data. Where data were incomplete or unclear, a third
      reviewer resolved conflicts and/or trial authors were contacted for further
      details. MAIN RESULTS: Three trials that examined cotrimoxazole prophylaxis and
      involving 268 adults were included. Meta-analysis of these studies found a
      beneficial effect of using a desensitization protocol over a rechallenge protocol
      at six months of follow-up for preventing discontinuation of cotrimoxazole
      (number needed to treat (NNT) 7.14, 95% confidence interval (CI) 4.0-33.0), and
      for lower incidence of overall hypersensitivity (NNT 4.55, 95% CI 3.03-9.09). No
      severe hypersensitivity reactions occurred for either protocol in the three
      studies. AUTHORS' CONCLUSIONS: In the small trials included in this review, when
      compared to cotrimoxazole rechallenge for prophylaxis of opportunistic
      infections, cotrimoxazole desensitization resulted in fewer treatment
      discontinuations and overall adverse reactions in HIV-infected patients with a
      previous history of mild or moderate hypersensitivity to cotrimoxazole.
      Paediatric data and trials in resource-poor settings are urgently required.
      Further randomised controlled trials are also needed for the treatment of
      opportunistic infections, treating-through, adjunctive medications, and different
      desensitization-dosing schedules.

PMID- 17443609
TI  - Routine abdominal drainage for uncomplicated open cholecystectomy.
AB  - BACKGROUND: Cholecystectomy is the removal of gallbladder and is performed mainly
      for symptomatic gallstones. Although laparoscopic cholecystectomy is currently
      preferred over open cholecystectomy for elective cholecystectomy, reports of
      randomised clinical trials comparing the choice of cholecystectomy (open or
      laparoscopic) in acute cholecystitis are still being conducted. Drainage in open
      cholecystectomy is a matter of considerable debate. Surgeons use drains primarily
      to prevent subhepatic abscess or bile peritonitis from an undrained bile leak.
      Critics of drain condemn drain use as it increases wound and chest infection.
      OBJECTIVES: To assess the benefits and harms of routine abdominal drainage in
      uncomplicated open cholecystectomy. 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 April 2006. SELECTION CRITERIA: We included
      randomised clinical trials comparing 'no drain' versus 'drain' in patients who
      had undergone uncomplicated open cholecystectomy (irrespective of language,
      publication status, and the type of drain). Randomised clinical trials comparing
      one drain with another were also included. DATA COLLECTION AND ANALYSIS: We
      collected the data on the characteristics and methodological quality of each
      trial, number of abdominal collections requiring different treatments, bile
      peritonitis, wound infection, chest complications, and hospital stay from each
      trial. We analysed the data with both the fixed-effect and the random-effects
      models using RevMan Analysis. For each outcome, we calculated the odds ratio (OR)
      with 95% confidence intervals (CI) based on intention-to-treat analysis. MAIN
      RESULTS: Twenty eight trials involving 3659 patients were included. There were 20
      comparisons of 'no drain' versus 'drain' and 12 comparisons of one drain with
      another. There was no statistically significant difference in mortality, bile
      peritonitis, total abdominal collections, abdominal collections requiring
      different treatments, or infected abdominal collections. 'No drain' group had
      statistically significant lower wound infection (OR 0.61, 95% CI 0.43 to 0.87)
      and statistically significant lower chest infection (OR 0.59, 95% CI 0.42 to
      0.84) than drain group. We found no significant differences between different
      types of drains. AUTHORS' CONCLUSIONS: Drains increase the harms to the patient
      without providing any additional benefit for patients undergoing open
      cholecystectomy and should be avoided in open cholecystectomy.

PMID- 17443610
TI  - Multidisciplinary rehabilitation for adults with multiple sclerosis.
AB  - BACKGROUND: Multidisciplinary rehabilitation (MD) is an important component of
      symptomatic and supportive treatment for Multiple sclerosis (MS), but evidence
      base for its effectiveness is yet to be established. OBJECTIVES: To assess the
      effectiveness of organized MD rehabilitation in adults with MS. To explore
      rehabilitation approaches that are effective in different settings and the
      outcomes that are affected. SEARCH STRATEGY: The sources used included: Cochrane
      Central Register of Controlled Trials "CENTRAL", MEDLINE (1966- 2005), CINAHL
      (1982- 2005), PEDro (1990- 2005), EMBASE (1988- 2005), the Cochrane
      Rehabilitation and Related Therapies Field trials Register and the National
      Health Service National Research Register (NRR). SELECTION CRITERIA: Randomized
      and controlled clinical trials that compared MD rehabilitation with routinely
      available local services or lower levels of intervention; or trials comparing
      interventions in different settings or at different levels of intensity. DATA
      COLLECTION AND ANALYSIS: Three reviewers selected trials and rated their
      methodological quality independently. A 'best evidence' synthesis based on
      methodological quality was performed. Trials were grouped in terms of setting and
      type of rehabilitation and duration of patient follow up. MAIN RESULTS: Eight
      trials (7 RCTs; 1 CCT) (747 participants and 73 caregivers) were identified.
      Seven RCTs scored well and one CCT scored poorly on the methodological quality
      assessment. There was 'strong evidence' that despite no change in the level of
      impairment, inpatient MD rehabilitation can produce short-term gains at the
      levels of activity (disability) and participation for patients with MS. For
      outpatient and home-based rehabilitation programmes there was 'limited evidence'
      for short-term improvements in symptoms and disability with high intensity
      programmes, which translated into improvement in participation and quality of
      life. For low intensity programmes conducted over a longer period there was
      strong evidence for longer-term gains in quality of life; and also limited
      evidence for benefits to carers. Although some studies reported potential for
      cost-savings, there is no convincing evidence regarding the long-term cost
      effectiveness of these programmes. It was not possible to suggest best 'dose' of
      therapy or supremacy of one therapy over another. This review highlights the
      limitations of RCTs in rehabilitation settings and need for better designed
      randomized and multiple centre trials. AUTHORS' CONCLUSIONS: MD rehabilitation
      programmes do not change the level of impairment, but can improve the experience
      of people with MS in terms of activity and participation. Regular evaluation and
      assessment of these persons for rehabilitation is recommended. Further research
      into appropriate outcome measures, optimal intensity, frequency, cost and
      effectiveness of rehabilitation therapy over a longer time period is needed.
      Future research in rehabilitation should focus on improving methodological and
      scientific rigour of clinical trials.

PMID- 17443611
TI  - Lamotrigine for acute and chronic pain.
AB  - BACKGROUND: Anticonvulsant medicines have a place in the treatment of neuropathic
      pain (pain due to nerve damage). This review looks at the evidence for the pain
      relieving properties of lamotrigine. OBJECTIVES: To assess the analgesic efficacy
      and adverse effects of the anticonvulsant lamotrigine for acute and chronic pain.
      SEARCH STRATEGY: Randomised Controlled Trials (RCTs) of lamotrigine (and key
      brand names Lamictal, Lamictin, Neurium) in acute, chronic or cancer pain were
      identified from MEDLINE (1966 to August 2006), EMBASE 1994 to August 2006 and the
      CENTRAL register on The Cochrane Library (Issue 3, 2006). Additional reports were
      sought from the reference list of the retrieved papers. SELECTION CRITERIA: RCTs
      investigating the use of lamotrigine (any dose and by any route) for treatment of
      acute or chronic pain. Assessment of pain intensity or pain relief, or both,
      using validated scales. Participants were adults aged 18 and over. Only full
      journal publication articles were included. DATA COLLECTION AND ANALYSIS:
      Dichotomous data were used to calculate relative risk with 95% confidence
      intervals using a fixed effects model unless significant statistical
      heterogeneity was found. Continuous data was also reported where available. Meta
      analysis was undertaken using a fixed effect model unless significant
      heterogeneity was present (I(2) >50%) in which case a random effects model was
      used. Numbers-needed-to-treat (NNTs) were calculated as the reciprocal of the
      absolute risk reduction. For unwanted effects, the NNT becomes the number-needed
      to-harm (NNH) and was calculated. MAIN RESULTS: Sixteen studies were identified.
      Nine studies were excluded. No studies for acute pain were identified. The seven
      included studies involved 502 participants, all for neuropathic pain. The studies
      covered the following conditions: central post stroke pain (1), diabetic
      neuropathy (1), HIV related neuropathy (2), intractable neuropathic pain (1),
      spinal cord injury related pain (1) and trigeminal neuralgia (1). The studies
      included participants in the age range of 26 to 77 years. Only one study for HIV
      related neuropathy had a statistically significant result for a sub group of
      patients on anti-retroviral therapy; this result is unlikely to be clinically
      significant NNT 4.3 (95% CI 2.3 to 37). Approximately 7% of participants taking
      lamotrigine reported a skin rash. AUTHORS' CONCLUSIONS: Given the availability of
      more effective treatments including anticonvulsants and antidepressant medicines,
      lamotrigine does not have a significant place in therapy at present. The limited
      evidence currently available suggests that lamotrigine is unlikely to be of
      benefit for the treatment of neuropathic pain.

PMID- 17443612
TI  - Pain relief in hysterosalpingography.
AB  - BACKGROUND: Hysterosalpingography (HSG) is a method of testing for tubal patency.
      Various pharmacological strategies are available that may reduce the pain during
      the procedure. OBJECTIVES: To compare the effectiveness of different types of
      pharmacological interventions for pain relief in women undergoing
      hysterosalpingography (HSG) for investigation of subfertility. SEARCH STRATEGY:
      This review has drawn on the search strategy developed for the Menstrual
      Disorders and Subfertility Group. In addition MEDLINE and EMBASE were searched up
      to July 2006. SELECTION CRITERIA: All randomised controlled trials investigating
      the pharmacological interventions for pain relief during HSG were investigated.
      DATA COLLECTION AND ANALYSIS: Data were extracted independently by the first two
      authors. Differences of opinion were registered and resolved by the third author.
      Results for each study were expressed as mean pain score and standard error of
      the mean with 95% confidence intervals. MAIN RESULTS: The included eight trials
      reported on 570 women undergoing HSG.Overall, there was no evidence of benefit of
      using any analgesia compared with placebo for pain relief during the procedure
      (standard mean difference (SMD) of -0.05 (95%CI -0.25 to 0.14) or up to 29
      minutes after HSG SMD 0.17, (95%CI -1.00 to 1.34)). Four RCTs involving 219 women
      found evidence of benefit with any analgesia in comparison to placebo for pain
      relief more than 30 minutes after HSG, with the SMD of -0.82(95%CI-1.18 to 
      0.45). One RCT involving 91 women compared the effectiveness of opioid analgesics
      versus non-opioid analgesics and reported no evidence of difference in pain
      relief at any stage of the procedure. One RCT involving 20 women compared the use
      of topical analgesia with a paracervical block, with analysis demonstrating more
      benefit to be gained from using topical analgesia during HSG, with the SMD of 
      2.03 (95%Cl-3.16 to -0.91). AUTHORS' CONCLUSIONS: There is little evidence of
      benefit in terms of pain relief of any of the interventions considered in this
      study during or immediately after HSG. However, there is limited evidence of pain
      reduction 30 minutes after the procedure. Further RCTs should consider the role
      of non steroidal antiinflammatories (NSAIDs) and intrauterine anaesthetic during
      HSG.

PMID- 17443613
TI  - Antibiotics for treating acute chest syndrome in people with sickle cell disease.
AB  - BACKGROUND: The clinical presentation of acute chest syndrome is similar whether
      due to infectious or non-infectious causes, thus antibiotics are usually
      prescribed to treat all episodes. Many different bacteria have been implicated as
      causative agents of acute chest syndrome. There is no standardized approach to
      antibiotic therapy and treatment is likely to vary from country to country. Thus,
      there is a need to identify the efficacy and safety of different antibiotic
      treatment approaches for people with sickle cell disease suffering from acute
      chest syndrome. OBJECTIVES: To determine whether an empirical antibiotic
      treatment approach (used either alone or in combination): (a) is effective in
      treating acute chest syndrome compared to placebo or standard treatment; (b) is
      safe in treating acute chest syndrome compared to placebo or standard treatment;
      (c) differs dependent on the regimen used in treating acute chest syndrome differ
      from each other with respect to efficacy and safety; and (d) varies between
      different age groups, regions or countries with respect to efficacy and safety.
      SEARCH STRATEGY: We searched The Group's Haemoglobinopathies Trials Register,
      which comprises references identified from comprehensive electronic database
      searches and handsearching of relevant journals and abstract books of conference
      proceedings. We also searched the LILACS database (1982 to May 2006) and the
      website: http://www.clinicaltrials.gov (May 2006). Date of most recent search of
      the Haemoglobinopathies Trials Register: February 2007. SELECTION CRITERIA: We
      searched for published or unpublished randomised controlled trials. DATA
      COLLECTION AND ANALYSIS: Each author intended to independently extract data and
      assess trial quality by standard Cochrane Collaboration methodologies, but no
      eligible randomized controlled trials were identified. MAIN RESULTS: We were
      unable to find any randomised controlled trials on antibiotic treatment
      approaches for acute chest syndrome in people with sickle cell disease. AUTHORS'
      CONCLUSIONS: We were unable to identify randomised controlled trials on efficacy
      and safety of the antibiotic treatment approaches for people with sickle cell
      disease suffering from acute chest syndrome. Randomised controlled trials are
      needed to establish the optimum antibiotic treatment for this condition.

PMID- 17443614
TI  - Piracetam for reducing the incidence of painful sickle cell disease crises.
AB  - BACKGROUND: Sickle cell disease is one of the most common genetic disorders.
      Sickle cell crises in which irregular and dehydrated cells contribute to blocking
      of blood vessels are characterised by episodes of pain. Treatment is mainly
      supportive and symptomatic. In vitro studies with piracetam indicate that it has
      the potential for inhibition and a reversal of the process of sickling of
      erythrocytes. OBJECTIVES: To assess the effectiveness of piracetam for reducing
      the incidence of painful sickle cell disease crises. SEARCH STRATEGY: We searched
      the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies
      Trials Register which comprises of references identified from comprehensive
      electronic database searches and handsearches of relevant journals and abstract
      books of conference proceedings. Date of the last search of the Group's
      Haemoglobinopathies Trials Register: February 2007. SELECTION CRITERIA:
      Randomised controlled trials comparing orally administered piracetam to placebo
      or standard care in people, of all ages and both sexes, with sickle cell disease.
      DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality
      and extracted data. Trial authors were contacted for additional information.
      Adverse effects data were collected from the trials. MAIN RESULTS: Three trials
      involving 169 participants were included in the review. A limited amount of data
      addressing some of the primary and some of the secondary outcomes were provided,
      but data were incomplete and based on unvalidated assumptions used in the
      evaluation of outcomes. One trial reported a reduction in the number of pain
      crises and their severity with active intervention than placebo but presented no
      data to confirm these results. A second trial presented a monthly global pain
      score based on the number of sickle cell crises and severity of pain but included
      no separate data for these primary outcomes. Although there was no significant
      difference between the piracetam and placebo periods for the number of days of
      hospitalisation (P = 0.87) in one trial, inconsistencies in the criteria
      necessary for hospitalisation during sickle crises did not permit accurate
      conclusions to be drawn. Two of the trials reported participant satisfaction with
      piracetam but provided no details as to how this satisfaction had been assessed.
      There were no reports of toxicity or adverse effects with piracetam other than
      one participant who experienced dizziness. AUTHORS' CONCLUSIONS: The small number
      of included trials and their poor methodological quality provided insufficient
      reliable evidence to support the routine use of this medication for preventing
      the incidence of painful sickle cell disease crises.

PMID- 17443615
TI  - Steroidal contraceptives: effect on carbohydrate metabolism in women without
      diabetes mellitus.
AB  - BACKGROUND: Many hormonal contraceptives have been associated with changes in
      carbohydrate metabolism. Alterations may include decreased glucose tolerance and
      increased insulin resistance, which are risk factors for Type 2 diabetes mellitus
      and cardiovascular disease. These issues have been raised with progestin-only
      contraceptives as well as contraceptives containing estrogen. Such potential
      effects could influence recommendations for, and use of, these widely used and
      effective contraceptives. OBJECTIVES: To evaluate the effect of hormonal
      contraceptives on carbohydrate metabolism in healthy women and those at risk for
      diabetes due to overweight. SEARCH STRATEGY: We searched the computerized
      databases MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS for studies of hormonal
      contraceptives and carbohydrate metabolism. The latest search was conducted in
      March 2006. We wrote to investigators for information about other published or
      unpublished trials. SELECTION CRITERIA: All randomized controlled trials (RCTs)
      were considered if they examined carbohydrate metabolism in women without
      diabetes who used hormonal contraceptives for contraception. Interventions
      included comparisons of a hormonal contraceptive with a placebo, a non-hormonal
      contraceptive, or another hormonal contraceptive that differed in drug, dosage,
      or regimen. Interventions included at least three cycles. Outcomes included
      glucose and insulin levels, which were generally reported as fasting value or
      response to an oral glucose tolerance test. DATA COLLECTION AND ANALYSIS: We
      assessed for inclusion all titles and abstracts identified during the literature
      searches with no language limitations. The data were abstracted and the
      information was entered into RevMan. Studies were examined for methodological
      quality. For continuous variables, the weighted mean difference was computed with
      95% confidence interval (CI) using a fixed-effect model. For dichotomous
      outcomes, the Peto odds ratio (OR) with 95% CI was calculated. MAIN RESULTS: A
      total of 39 trials met the inclusion criteria. No study stratified by body weight
      (normal-weight versus overweight women). Results for desogestrel were often
      favorable regarding carbohydrate metabolism but inconsistent overall. Glucose and
      insulin means were more favorable for norethisterone in studies of progestin-only
      contraceptives. For other progestins, little or no difference was noted across
      trials. AUTHORS' CONCLUSIONS: Current evidence suggests that hormonal
      contraceptives have limited effect on carbohydrate metabolism in women without
      diabetes. Strong statements cannot be made, though, due to having few studies
      that compared any particular types of contraceptives. Many trials had small
      numbers of participants and some had large losses to follow up. Most studies had
      poor reporting of methods. No information was available regarding the effects
      among women who were overweight.

PMID- 17443616
TI  - Interventions for treating AIDS-associated Hodgkin s lymphoma in treatment-naive
      adults.
AB  - BACKGROUND: Hodgkin's disease (HD) is the most common non-AIDS-defining
      malignancy in HIV-infected patients. Its unusually aggressive tumour behaviour
      includes a higher frequency of unfavourable histologic subtypes, high-stage and
      extranodal involvement by the time of presentation (anal canal, stomach), and
      poor therapeutic outcome, in comparison with HD outside the HIV setting. The
      optimal therapeutic strategy is still controversial, and median overall survival
      is short, ranging from 12 to 18 months. Thus, there is a need to identify the
      efficacy and safety of different interventions for AIDS-associated HD on overall
      survival and disease-free survival in treatment-naive adults with AIDS.
      OBJECTIVES: To assess the effects of different interventions for treating AIDS
      associated Hodgkin's disease including chemotherapy, bone marrow transplantation
      (BMT), and gene therapy on overall survival and disease-free survival in
      treatment-naive adults with AIDS. SEARCH STRATEGY: We searched The Cochrane
      HIV/AIDS Group Trials Register (September 2006), which comprises references
      identified from comprehensive electronic database searches and handsearching of
      relevant journals and abstract books of conference proceedings. We also searched
      the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane
      Library (Issue 3, 2006), MEDLINE (1966 to September 2006), EMBASE (1974 to
      September 2006) LILACS (1982 to September 2006), ISI Web of Knowledge (1993 to
      September 2006), and AIDSearch (1980 to December 2006). Date of most recent
      search: December 2006. SELECTION CRITERIA: We searched for published or
      unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: We
      intended to summarise data by standard Cochrane Collaboration methodologies, but
      no eligible randomised controlled trials were identified. MAIN RESULTS: We were
      unable to find any randomised controlled trials of interventions for treating
      AIDS-associated HD in treatment-naive adults with AIDS. AUTHORS' CONCLUSIONS:
      Randomised controlled trials are needed to establish the efficacy and safety of
      interventions for treating AIDS-associated HD in treatment-naive adults with
      AIDS.

PMID- 17443617
TI  - Resorbable versus titanium plates for orthognathic surgery.
AB  - BACKGROUND: Recognition of some of the limitations of titanium plates and screws
      used for the fixation of bones has led to the development of plates manufactured
      from bioresorbable materials. Whilst resorbable plates appear to offer clinical
      advantages over metal plates in orthognathic surgery, 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 used during
      orthognathic surgery. SEARCH STRATEGY: We searched the following databases:
      Cochrane Oral Health Group Trials Register (to 26th January 2006); the Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2005, Issue
      4); MEDLINE (without filter) (from 1966 to 26th January 2006); and EMBASE
      (without filter) (from 1980 to 26th January 2006). SELECTION CRITERIA: Randomised
      controlled trials comparing resorbable versus titanium fixation systems used for
      orthognathic surgery. DATA COLLECTION AND ANALYSIS: Clinical heterogeneity
      between the included trials precluded pooling of data, and only a descriptive
      summary is presented. MAIN RESULTS: This review included two trials, involving
      103 participants, one compared titanium with resorbable plates and screws and the
      other titanium with resorbable screws, both provided very limited data for the
      primary outcomes of this review. All patients in one trial suffered mild to
      moderate postoperative discomfort with no statistically significant difference
      between the two plating groups at different follow-up times. Mean scores of
      patient satisfaction were 7.43 to 8.63 (range 0 to 10) with no statistically
      significant difference between the two groups throughout follow up. Adverse
      effects reported in one study were two plate exposures in each group occurring
      between the third and ninth months. Plate exposures occurred mainly in the
      posterior maxillary region, except for one titanium plate exposure in the
      mandibular premolar region. Known causes of infection were associated with
      loosened screws and wound dehiscence with no statistically significant difference
      in the infection rate between titanium (3/196), and resorbable (3/165) plates P =
      0.83 (published as P = 0.67). AUTHORS' CONCLUSIONS: This review provides some
      evidence to show that there is no statistically significant difference in
      postoperative discomfort, level of patient satisfaction, plate exposure or
      infection for plate and screw fixation using either titanium or resorbable
      materials in orthognathic surgery.

PMID- 17443618
TI  - Steroid hormones for contraception in women with sickle cell disease.
AB  - BACKGROUND: Whether steroid contraceptives are appropriate for women with
      homozygous sickle cell (SS) disease remains unresolved. Historically, women with
      SS disease have experienced difficult pregnancies, characterized by high rates of
      maternal mortality and morbidity and poor infant outcomes. Unresolved questions
      about steroidal contraceptives in women with SS disease include whether using
      them may promote blood clots. OBJECTIVES: To assess the safety of steroid
      hormones in this setting, we retrieved and analyzed all randomized controlled
      trials that examined steroid hormones for contraception in women with SS disease.
      SEARCH STRATEGY: We searched the computerized databases Cochrane Central Register
      of Controlled Trials (CENTRAL), MEDLINE, POPLINE and EMBASE (each from its
      inception to November, 2005) for randomized controlled trials of steroid hormone
      use for contraception in women with SS disease. We examined the reference list of
      each trial as well as that of review articles. SELECTION CRITERIA: We included
      any randomized controlled trial in any language that compared steroid hormones
      for contraception with another contraceptive or placebo. Frequency or intensity
      of sickle pain crises must have been reported as an outcome. DATA COLLECTION AND
      ANALYSIS: We assessed for inclusion all titles and abstracts found. We evaluated
      the methodological quality of the trial found for potential biases by
      qualitatively assessing the study design, randomization method, allocation
      concealment, blinding, premature discontinuation rates, and loss to follow-up
      rates. We entered trial results in RevMan and reported Peto odds ratios with 95%
      confidence intervals for dichotomous outcomes, such as occurrence of sickle pain
      crises. MAIN RESULTS: Only one trial met the inclusion criteria. Twenty-five
      patients were randomized to three monthly depo-medroxyprogesterone acetate (DMPA)
      or intramuscular saline placebo injections in a crossover design. A six-month
      washout period was implemented before the crossover; however, pharmacological
      evidence indicates that levels of DMPA may be detected for more than 200 days
      after the injection. During DMPA use, women were less likely to experience
      painful sickle episodes (OR 0.23; 95% CI 0.05 to 1.02). No trial involved
      estrogen products. AUTHORS' CONCLUSIONS: The limited available data suggest that
      DMPA is a safe contraceptive option for women in SS disease. In addition to
      providing effective contraception, DMPA may reduce sickle pain crises.

PMID- 17443619
TI  - Pneumococcal vaccines for children and adults with bronchiectasis.
AB  - BACKGROUND: Bronchiectasis is increasingly recognized as a major cause of
      respiratory morbidity especially in developing countries. Even in affluent
      countries, bronchiectasis is increasingly seen in some community subsections
      (e.g. Aboriginal communities) and occurs as a comorbidity and disease modifier in
      respiratory diseases such as chronic obstructive pulmonary disease (COPD).
      Respiratory exacerbations in people with bronchiectasis is associated with
      reduced quality of life, accelerated pulmonary decline, hospitalisation and even
      death. Conjugate pneumococcal vaccine is part of the routine infant immunisation
      schedule in many countries. Current recommendations for additional pneumococcal
      vaccination include children and adults with chronic suppurative disease.
      OBJECTIVES: To evaluate the effectiveness of pneumococcal vaccine as routine
      management in children and adults with bronchiectasis in (a) reducing the
      severity and frequency of respiratory exacerbations and (b) pulmonary decline.
      SEARCH STRATEGY: The Cochrane Register of Controlled Trials (CENTRAL), the
      Cochrane Airways Group Specialised Register, MEDLINE and EMBASE databases were
      searched by the Cochrane Airways Group. Pharmaceutical manufacturers of
      pneumococcal vaccines were also contacted. The latest searches were performed in
      October 2006. SELECTION CRITERIA: All randomised controlled trials that utilised
      pneumococcal vaccine on children and adults with bronchiectasis. All types of
      pneumococcal vaccines were included. DATA COLLECTION AND ANALYSIS: Results of
      searches were reviewed against pre-determined criteria for inclusion. No eligible
      trials were identified and thus no data was available for analysis. One small non
      randomised controlled trial in children was reported. MAIN RESULTS: No randomised
      controlled trials pertaining effectiveness of pneumococcal vaccine as routine
      management in children and adults with bronchiectasis were found. A benefit in
      elimination of Strep. pneumoniae in the sputum was found in a non-randomised
      trial in children but no clinical effect was described. AUTHORS' CONCLUSIONS: At
      present, there is a lack of reliable evidence to support or refute the routine
      use of pneumococcal vaccine as routine management in children and adults with
      bronchiectasis. Randomised controlled trials examining the efficacy of this
      intervention using various vaccine types in different age groups are needed.
      Until further evidence is available, it is recommended that health providers
      adhere to national guidelines.

PMID- 17443620
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 maintaining 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 relapse rate and
      secondary outcomes were 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-analysis was 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 to
      address heterogeneity. MAIN RESULTS: Four studies were eligible for inclusion.
      There was a non statistically significant benefit of n-3 therapy for maintaining
      remission (RR 0.64; 95%CI 0.4 to 1.03; P = 0.07). However, the studies were both
      clinically and statistically heterogeneous (P = 0.01, I(2) = 72%). Three studies
      used enteric coated capsules (positive effects) and one ordinary gelatin capsules
      (no advantage). Subgroup analyses of studies which used enteric coated capsules
      revealed a statistically significant benefit for maintenance of remission (RR
      0.49; 95% CI 0.35 to 0.69; RD 0.31; 95% CI 0.19 to 0.43); number needed to treat
      to prevent relapse in 1 year was 3 (95% CI 2 to 5; I(2) = 19%). However, the
      total number of patients enrolled in these studies was small (n = 166). No
      significant adverse events were recorded in any of the studies and not enough
      data were available to analyze the other secondary outcomes. AUTHORS'
      CONCLUSIONS: Omega 3 fatty acids are safe and may be effective for maintenance of
      remission in CD when used in enteric coated capsules. However, there are not
      sufficient data to recommend the routine use of n-3 for maintenance of remission
      in CD. The small number of patients in the included studies warrants further
      larger RCTs.

PMID- 17443621
TI  - Problem solving skills for schizophrenia.
AB  - BACKGROUND: The severe and long-lasting symptoms of schizophrenia are often the
      cause of severe disability. Environmental stress such as life events and the
      practical problems people face in their daily can worsen the symptoms of
      schizophrenia. Deficits in problem solving skills in people with schizophrenia
      affect their independent and interpersonal functioning and impair their quality
      of life. As a result, therapies such as problem solving therapy have been
      developed to improve problem solving skills for people with schizophrenia.
      OBJECTIVES: To review the effectiveness of problem solving therapy compared with
      other comparable therapies or routine care for those with schizophrenia. SEARCH
      STRATEGY: We searched the Cochrane Schizophrenia Group's Register (September
      2006), which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE,
      MEDLINE and PsycINFO. We inspected references of all identified studies for
      further trials. SELECTION CRITERIA: We included all clinical randomised trials
      comparing problem solving therapy with other comparable therapies or routine
      care. DATA COLLECTION AND ANALYSIS: We extracted data independently. For
      homogenous dichotomous data we calculated random effects, relative risk (RR), 95%
      confidence intervals (CI) and, where appropriate, numbers needed to treat (NNT)
      on an intention-to-treat basis. For continuous data, we calculated weighted mean
      differences (WMD) using a random effects statistical model. MAIN RESULTS: We
      included only three small trials (n=52) that evaluated problem solving versus
      routine care, coping skills training or non-specific interaction. Inadequate
      reporting of data rendered many outcomes unusable. We were unable to undertake
      meta-analysis. Overall results were limited and inconclusive with no significant
      differences between treatment groups for hospital admission, mental state,
      behaviour, social skills or leaving the study early. No data were presented for
      global state, quality of life or satisfaction. AUTHORS' CONCLUSIONS: We found
      insufficient evidence to confirm or refute the benefits of problem solving
      therapy as an additional treatment for those with schizophrenia. The small number
      of participants, the quality of reporting of methods and results were of concern.
      More trials with adequate reporting of methods to minimize bias, adequately
      powered, with validated, reliable and clinically meaningful outcomes are needed
      to provide robust evidence to guide policy and practice.

PMID- 17443622
TI  - Oral anticoagulation for prolonging survival in patients with cancer.
AB  - BACKGROUND: A number of basic research and clinical studies have led to the
      hypothesis that oral anticoagulants may improve the survival of patients with
      cancer through an antitumour effect in addition to their antithrombotic effect.
      OBJECTIVES: To evaluate the effectiveness and safety of oral anticoagulation
      (including vitamin K antagonists and ximelagatran) as an intervention to improve
      survival of patients with cancer. SEARCH STRATEGY: A comprehensive search for
      studies of anticoagulation in cancer patients including (1) a January 2007
      electronic search of the following databases: Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, EMBASE, ISI the Web of Science; (2) hand
      search of the American Society of Clinical Oncology (starting with its first
      volume, 1982) and of the American Society of Hematology (starting with its 2003
      issue); (3) checking of references of included studies; and (4) use of "related
      article" feature in PubMed. SELECTION CRITERIA: Randomized clinical trials (RCTs)
      comparing vitamin K antagonist or ximelagatran to no intervention or placebo in
      cancer patients without clinical evidence of venous thromboembolism. DATA
      COLLECTION AND ANALYSIS: Using a standardized data form we extracted data on
      methodological quality, participants, interventions and outcome of interest that
      included all cause mortality, symptomatic deep venous thrombosis, symptomatic
      pulmonary embolism, major bleeding and minor bleeding. MAIN RESULTS: Of 3986
      identified citations five RCTs fulfilled the inclusion criteria. Warfarin was the
      oral anticoagulant in all of these RCTs and it was compared to either placebo or
      no intervention. The overall methodological quality of these RCTs was acceptable.
      The effect of warfarin on reduction in mortality was not statistically
      significant at six months (Relative risk (RR) = 0.96; 95% CI 0.80 to 1.16), at
      one year (RR = 0.95; 95% CI 0.86 to 1.05) at 2 years (RR = 0.97; 95% CI 0.87 to
      1.08) or at five years (RR 0.91; 95% CI 0.83 to 1.01). In the subgroup of
      patients with small cell lung cancer (SCLC), warfarin reduced mortality at six
      months (RR = 0.69; 95% CI 0.50 to 0.96) but not at one year (RR = 0.88; 95% CI
      0.77 to 1.01). This six month mortality benefit was statistically significant in
      the subgroup of extensive SCLC (RR = 0.65; 95% CI 0.45 to 0.93) but not in the
      subgroup of limited SCLC (RR = 0.68; 95% CI 0.36 to 1.28). One study assessed the
      effect of warfarin on venous thromboembolism and showed a RR reduction of 85% (p
      = 0.031). Warfarin increased both major bleeding (RR = 4.24; 95% CI 1.85 to 9.68)
      and minor bleeding (RR = 3.34; 95% CI 1.66 to 6.74). Warfarin increased the risk
      of major bleeding (RR 5.46; 95% CI 3.04 to 9.81) and minor bleeding (RR 4.01; 95%
      CI 1.30 to 12.42) also in patients with SCLC. There was no evidence for a
      significant reduction in mortality in any other cancer subtype. AUTHORS'
      CONCLUSIONS: Existing evidence does not suggest a mortality benefit from oral
      anticoagulation in patients with cancer. In patients with SCLC, the evidence
      suggests a survival benefit at six months from warfarin particularly when the
      disease is extensive. The decision for a patient with extensive SCLC to start
      warfarin for survival benefit should balance that benefit with the downsides of
      increased bleeding risk in light of patient values for these outcomes.

PMID- 17443623
TI  - Nitric oxide for preventing pre-eclampsia and its complications.
AB  - BACKGROUND: Pre-eclampsia, a multisystem disorder of pregnancy characterised by
      high blood pressure and protein in the urine, is associated with endothelial
      dysfunction. Nitric oxide mediates many functions of the endothelium, including
      vasodilatation and inhibition of platelet aggregation. Pre-eclampsia may be
      associated with nitric oxide deficiency, but the evidence to support this
      suggestion is contradictory. Nevertheless, it has been hypothesised that agents
      which increase nitric oxide may prevent pre-eclampsia. OBJECTIVES: To assess the
      effectiveness and safety of nitric oxide donors and precursors for preventing pre
      eclampsia and its complications. SEARCH STRATEGY: We searched the Cochrane
      Pregnancy and Childbirth Group's Trials Register (November 2006), CENTRAL (The
      Cochrane Library 2006, Issue 3), and EMBASE (2002 to December 2004). SELECTION
      CRITERIA: Studies were included if they were randomised trials evaluating nitric
      oxide donors or precursors for preventing pre-eclampsia and its complications.
      DATA COLLECTION AND ANALYSIS: Both review authors independently assessed studies
      for inclusion. Data were extracted and double checked for accuracy. MAIN RESULTS:
      Six trials (310 women) were included. Four were of good quality and two were of
      uncertain quality. Four trials (170 women) compared nitric oxide donors (glyceryl
      trinitrate) or precursors (L-arginine) with either placebo or no intervention.
      There are insufficient data for reliable conclusions about the effects on pre
      eclampsia (four trials, 170 women; relative risk (RR) 0.83, 95% confidence
      interval (CI) 0.49 to 1.41) or its complications. One trial (36 women) compared a
      nitric oxide donor with nifedipine, and another (76 women) compared it with
      antiplatelet agents. Both were too small for reliable conclusions about possible
      differential effects. Glyceryl trinitrate was associated with an increased risk
      of headache (two trials, 56 women; RR 6.85, 95% CI 1.42 to 33.04), and of
      stopping treatment (two trials, 56 women; RR 4.02, 95% CI 1.15 to 14.09) compared
      to placebo. However, the increase for both outcomes was due to an extreme result
      in one small trial (7/7 versus 0/9 for both outcomes). AUTHORS' CONCLUSIONS:
      There is insufficient evidence to draw reliable conclusions about whether nitric
      oxide donors and precursors prevent pre-eclampsia or its complications.

PMID- 17443624
TI  - Continuous ambulatory peritoneal dialysis versus automated peritoneal dialysis
      for end-stage renal disease.
AB  - BACKGROUND: Peritoneal dialysis (PD) can be performed either manually as in
      continuous ambulatory peritoneal dialysis (CAPD) or using mechanical devices as
      in automated PD (APD). APD has been considered to have several advantages over
      CAPD such as reduced incidence of peritonitis, mechanical complications and
      greater psychosocial acceptability. OBJECTIVES: To assess the comparative
      efficacy of CAPD and APD in patients who are dialysed for end-stage renal disease
      (ESRD). SEARCH STRATEGY: We searched MEDLINE, EMBASE, Cochrane Central Register
      of Controlled Trials (CENTRAL), Cochrane Renal Group's specialised register and
      CINAHL. Authors of included studies were contacted, reference lists of identified
      RCTs and relevant narrative reviews were screened. Date of most recent search:
      May 2006 SELECTION CRITERIA: RCTs comparing CAPD with APD in patients with ESRD.
      DATA COLLECTION AND ANALYSIS: Data were abstracted independently by two authors
      onto a standard form. Relative risk (RR) for dichotomous data and a mean
      difference (MD) for continuous data were calculated with 95% confidence intervals
      (CI). MAIN RESULTS: Three trials (139 patients) were included. APD did not differ
      from CAPD with respect to mortality (RR 1.49, 95% CI 0.51 to 4.37), risk of
      peritonitis (RR 0.75, 95% CI 0.50 to 1.11), switching from original PD modality
      to a different dialysis modality (RR 0.50, 95% CI 0.25 to 1.02), hernias (RR
      1.26, 95% interval 0.32 to 5.01), PD fluid leaks (RR 1.06, 95% CI 0.11 to 9.83),
      PD catheter removal (RR 0.64, 95% CI 0.27 to 1.48) or hospital admissions (RR
      0.96, 95% CI 0.43 to 2.17). There was no difference between either PD modality
      with respect to residual renal function (MD -0.17, 95% CI -1.66 to 1.32). One
      study found that peritonitis rates and hospitalisation were significantly less in
      patients on APD when results were expressed as episodes/patient-year. Another
      study found that patients on APD had significantly more time for work, family and
      social activities. AUTHORS' CONCLUSIONS: APD has not been shown to have
      significant advantages over CAPD in terms of important clinical outcomes. APD may
      however be considered advantageous in select group of patients such as in the
      younger PD population and those in employment or education due to its
      psychosocial advantages. There is a need for a RCT comparing CAPD with APD with
      sufficiently large patient numbers looking at important clinical outcomes
      including residual renal function, accompanied by an economic evaluation to
      clarify the relative clinical and cost-effectiveness of both modalities.

PMID- 17443625
TI  - Handsearching versus electronic searching to identify reports of randomized
      trials.
AB  - BACKGROUND: Systematic reviewers need to decide how best to reduce bias in
      identifying studies for their review. Even when journals are indexed in
      electronic databases, it can still be difficult to identify all relevant studies
      reported in these journals. Over 1700 journals have been or are being
      handsearched within The Cochrane Collaboration to identify reports of controlled
      trials in order to help address these problems. OBJECTIVES: To review
      systematically empirical studies, which have compared the results of
      handsearching with the results of searching one or more electronic databases to
      identify reports of randomized trials. SEARCH STRATEGY: Studies were sought from
      The Cochrane Methodology Register (The Cochrane Library, Issue 2, 2002), MEDLINE
      (1966 to Week 1 July 2002), EMBASE (1980 to Week 25 2002), AMED (1985 to June
      2002), BIOSIS (1985 to June 2002), CINAHL (1982 to June 2002), LISA (1969 to July
      2002) and PsycINFO (1972 to May 2002). Researchers who may have carried out
      relevant studies were contacted. SELECTION CRITERIA: A research study was
      considered eligible for this review if it compared handsearching with searching
      one or more electronic databases to identify reports of randomized trials. DATA
      COLLECTION AND ANALYSIS: The main outcome measure was the number of reports of
      randomized trials identified by handsearching as compared to electronic
      searching. Data were extracted on the electronic database searched, the
      complexity of electronic search strategy used, the characteristics of the journal
      reports identified, and the type of trial report identified. MAIN RESULTS: Thirty
      four studies were included. Handsearching identified between 92% to 100% of the
      total number of reports of randomized trials found in the various comparisons in
      this review. Searching MEDLINE retrieved 55%, EMBASE 49% and PyscINFO 67%. The
      retrieval rate of the electronic database varied depending on the complexity of
      the search. The Cochrane Highly Sensitive Search Strategy (HSSS) identified 80%
      of the total number of reports of randomized trials found, searches categorised
      as 'complex' (including the Cochrane HSSS) found 65% and 'simple' found 42%. The
      retrieval rate for an electronic search was higher when the search was restricted
      to English language journals; 62% versus 39% for journals published in languages
      other than English. When the search was restricted to full reports of randomized
      trials, the retrieval rate for an electronic search improved: a complex search
      strategy (including the Cochrane HSSS) retrieved 82% of the total number of such
      reports of randomized trials. AUTHORS' CONCLUSIONS: Handsearching still has a
      valuable role to play in identifying reports of randomized trials for inclusion
      in systematic reviews of health care interventions, particularly in identifying
      trials reported as abstracts, letters and those published in languages other than
      English, together with all reports published in journals not indexed in
      electronic databases. However, where time and resources are limited, searching an
      electronic database using a complex search (or the Cochrane HSSS) will identify
      the majority of trials published as full reports in English language journals,
      provided, of course, that the relevant journals have been indexed in the
      database.

PMID- 17443626
TI  - Technical editing of research reports in biomedical journals.
AB  - BACKGROUND: Most journals try to improve their articles by technical editing
      processes such as proof-reading, editing to conform to 'house styles' and
      grammatical conventions. Despite the considerable resources devoted to technical
      editing, we do not know whether it improves the accessibility of biomedical
      research findings or the utility of articles. OBJECTIVES: To assess the effects
      of technical editing on research reports in peer-reviewed biomedical journals.
      SEARCH STRATEGY: We searched the Cochrane Library Issue 1, 2001, MEDLINE (last
      searched February 2000), 12 other databases, handsearched 9 journals and checked
      relevant articles for further references. We also searched the Internet and
      contacted researchers and experts in the field. SELECTION CRITERIA: Prospective
      or retrospective comparative studies of technical editing processes applied to
      original research articles in biomedical journals. DATA COLLECTION AND ANALYSIS:
      Two reviewers independently assessed each study against the selection criteria
      and assessed the methodological quality of each study. One reviewer extracted the
      data, and the second reviewer repeated this. MAIN RESULTS: We located 18 studies
      addressing technical editing and 35 surveys of reference accuracy. Only two of
      the studies were randomized controlled trials. A 'package' of largely unspecified
      editorial processes applied between acceptance and publication was associated
      with improved readability in two studies and improved reporting quality in
      another two studies, while another study showed mixed results after stricter
      editorial policies were introduced. More intensive editorial processes were
      associated with fewer errors in abstracts and references. Providing instructions
      to authors was associated with improved reporting of ethics requirements in one
      study and fewer errors in references in two studies, but no difference was seen
      in the quality of abstracts in one randomized controlled trial. Structuring
      generally improved the quality of abstracts, but increased their length. The
      reference accuracy studies showed a median citation error rate of 39% and a
      median quotation error rate of 20%. AUTHORS' CONCLUSIONS: Surprisingly few
      studies have evaluated the effects of technical editing rigorously. However there
      is some evidence that the 'package' of technical editing used by biomedical
      journals does improve papers.

PMID- 17443627
TI  - Peer review for improving the quality of grant applications.
AB  - BACKGROUND: Grant giving relies heavily on peer review for the assessment of the
      quality of proposals but the evidence of effects of these procedures is scarce.
      OBJECTIVES: To estimate the effect of grant giving peer review processes on
      importance, relevance, usefulness, soundness of methods, soundness of ethics,
      completeness and accuracy of funded research. SEARCH STRATEGY: Electronic
      database searches and citation searches; researchers in the field were contacted.
      SELECTION CRITERIA: Prospective or retrospective comparative studies with two or
      more comparison groups assessing different interventions or one intervention
      against doing nothing. Interventions may regard different ways of screening,
      assigning or masking submissions, different ways of eliciting opinions or
      different decision making procedures. Only original research proposals and
      quality outcome measures were considered. DATA COLLECTION AND ANALYSIS: Studies
      were read, classified and described according to their design and study question.
      No quantitative analysis was performed. MAIN RESULTS: Ten studies were included.
      Two studies assessed the effect of different ways of screening submissions, one
      study compared open versus blinded peer review and three studies assessed the
      effect of different decision making procedures. Four studies considered agreement
      of the results of peer review processes as the outcome measure. Screening
      procedures appear to have little effect on the result of the peer review process.
      Open peer reviewers behave differently from blinded ones. Studies on decision
      making procedures gave conflicting results. Agreement among reviewers and between
      different ways of assigning proposals or eliciting opinions was usually high.
      AUTHORS' CONCLUSIONS: There is little empirical evidence on the effects of grant
      giving peer review. No studies assessing the impact of peer review on the quality
      of funded research are presently available. Experimental studies assessing the
      effects of grant giving peer review on importance, relevance, usefulness,
      soundness of methods, soundness of ethics, completeness and accuracy of funded
      research are urgently needed. Practices aimed to control and evaluate the
      potentially negative effects of peer review should be implemented meanwhile.

PMID- 17443628
TI  - Full publication of results initially presented in abstracts.
AB  - BACKGROUND: Abstracts of presentations at scientific meetings are usually
      available only in conference proceedings. If subsequent full publication of
      abstract results is based on the magnitude or direction of study results,
      publication bias may result. Publication bias, in turn, creates problems for
      those conducting systematic reviews or relying on the published literature for
      evidence. OBJECTIVES: To determine the rate at which abstract results are
      subsequently published in full, and the time between meeting presentation and
      full publication. To assess the association between study characteristics and
      full publication. SEARCH STRATEGY: We searched MEDLINE, EMBASE, The Cochrane
      Library, Science Citation Index, reference lists, and author files. Date of most
      recent search: June 2003. SELECTION CRITERIA: We included all reports that
      examined the subsequent full publication rate of biomedical results initially
      presented as abstracts or in summary form. Follow-up of abstracts had to be at
      least two years. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. We
      calculated the weighted mean full publication rate and time to full publication.
      Dichotomous variables were analyzed using relative risk and random effects
      models. We assessed time to publication using Kaplan-Meier survival analyses.
      MAIN RESULTS: Combining data from 79 reports (29,729 abstracts) resulted in a
      weighted mean full publication rate of 44.5% (95% confidence interval (CI) 43.9
      to 45.1). Survival analyses resulted in an estimated publication rate at 9 years
      of 52.6% for all studies, 63.1% for randomized or controlled clinical trials, and
      49.3% for other types of study designs.'Positive' results defined as any
      'significant' result showed an association with full publication (RR = 1.30; CI
      1.14 to 1.47), as did 'positive' results defined as a result favoring the
      experimental treatment (RR =1.17; CI 1.02 to 1.35), and 'positive' results
      emanating from randomized or controlled clinical trials (RR = 1.18, CI 1.07 to
      1.30). Other factors associated with full publication include oral presentation
      (RR = 1.28; CI 1.09 to 1.49); acceptance for meeting presentation (RR = 1.78; CI
      1.50 to 2.12); randomized trial study design (RR = 1.24; CI 1.14 to 1.36); and
      basic research (RR = 0.79; CI 0.70 to 0.89). Higher quality of abstracts
      describing randomized or controlled clinical trials was also associated with full
      publication (RR = 1.30, CI 1.00 to 1.71). AUTHORS' CONCLUSIONS: Only 63% of
      results from abstracts describing randomized or controlled clinical trials are
      published in full. 'Positive' results were more frequently published than not
      'positive' results.

PMID- 17443629
TI  - Methods to increase response rates to postal questionnaires.
AB  - BACKGROUND: Postal questionnaires are widely used for data collection in
      epidemiological studies but non-response reduces the effective sample size and
      can introduce bias. Finding ways to increase response rates to postal
      questionnaires would improve the quality of health research. OBJECTIVES: To
      identify effective strategies to increase response rates to postal
      questionnaires. SEARCH STRATEGY: We aimed to find all randomised controlled
      trials of strategies to increase response rates to postal questionnaires. We
      searched 14 electronic databases to February 2003 and manually searched the
      reference lists of relevant trials and reviews, and all issues of two journals.
      We contacted the authors of all trials or reviews to ask about unpublished
      trials. Where necessary, authors were also contacted to confirm methods of
      allocation used and to clarify results presented. We assessed the eligibility of
      each trial using pre-defined criteria. SELECTION CRITERIA: Randomised controlled
      trials of methods to increase response rates to postal questionnaires. DATA
      COLLECTION AND ANALYSIS: We extracted data on the trial participants, the
      intervention, the number randomised to intervention and comparison groups and
      allocation concealment. For each strategy, we estimated pooled odds ratios and
      95% confidence intervals in a random effects model. Evidence for selection bias
      was assessed using Egger's weighted regression method and Begg's rank correlation
      test and funnel plot. Heterogeneity among trial odds ratios was assessed using a
      chi-square test at a 5% significance level and the degree of inconsistency
      between trial results was quantified using I(2). MAIN RESULTS: We found 372
      eligible trials. The trials evaluated 98 different ways of increasing response
      rates to postal questionnaires and for 62 of these the combined trials included
      over 1,000 participants. We found substantial heterogeneity among trial results
      in half of the strategies. The odds of response were at least doubled using
      monetary incentives (odds ratio 1.99, 95% CI 1.81 to 2.18; heterogeneity
      p<0.00001, I(2)=78%), recorded delivery (2.04, 1.60 to 2.61; p=0.0004, I(2)=69%),
      a teaser on the envelope - e.g. a comment suggesting to participants that they
      may benefit if they open it (3.08, 1.27 to 7.44) and a more interesting
      questionnaire topic (2.44, 1.99 to 3.01; p=0.74, I(2)=0%). The odds of response
      were substantially higher with pre-notification (1.50, 1.29 to 1.74; p<0.00001,
      I(2)=90%), follow-up contact (1.44, 1.25 to 1.65; p<0.0001, I(2)=68%),
      unconditional incentives (1.61, 1.27 to 2.04; p<0.00001, I(2)=91%), shorter
      questionnaires (1.73, 1.47 to 2.03; p<0.00001, I(2)=93%), providing a second copy
      of the questionnaire at follow-up (1.51, 1.13 to 2.00; p<0.00001, I(2)=83%),
      mentioning an obligation to respond (1.61, 1.16 to 2.22; p=0.98, I(2)=0%) and
      university sponsorship (1.32, 1.13 to 1.54; p<0.00001, I(2)=83%). The odds of
      response were also increased with non-monetary incentives (1.13, 1.07 to 1.21;
      p<0.00001, I(2)=71%), personalised questionnaires (1.16, 1.07 to 1.26; p<0.00001,
      I(2)=67%), use of coloured as opposed to blue or black ink (1.39, 1.16 to 1.67),
      use of stamped return envelopes as opposed to franked return envelopes (1.29,
      1.18 to 1.42; p<0.00001, I(2)=72%), an assurance of confidentiality (1.33, 1.24
      to 1.42) and first class outward mailing (1.12, 1.02 to 1.23). The odds of
      response were reduced when the questionnaire included questions of a sensitive
      nature (0.94, 0.88 to 1.00; p=0.51, I(2)=0%), when questionnaires began with the
      most general questions (0.80, 0.67 to 0.96), or when participants were offered
      the opportunity to opt out of the study (0.76, 0.65 to 0.89; p=0.46, I(2)=0%).
      AUTHORS' CONCLUSIONS: Health researchers using postal questionnaires can increase
      response rates using the strategies shown to be effective in this systematic
      review.

PMID- 17443630
TI  - Outcomes of patients who participate in randomised controlled trials compared to
      similar patients receiving similar interventions who do not participate.
AB  - BACKGROUND: Some people believe that patients who take part in randomised
      controlled trials (RCTs) face risks that they would not face if they opted for
      non-trial treatment. Others think that trial participation is beneficial and the
      best way to ensure access to the most up to date physicians and treatments.
      OBJECTIVES: To assess the effects of patient participation in RCTs ('trial
      effects') independent both of the effects of the clinical treatments being
      compared ('treatment effects') and any differences between patients who
      participated in RCTs and those who did not. SEARCH STRATEGY: In May 2001, we
      searched The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE,
      EMBASE, The Cochrane Methodology Register, SciSearch and PsycINFO for potentially
      relevant studies. Our search yielded over 10,000 references. In addition, we
      reviewed the reference lists of relevant articles and wrote to over 250
      investigators to try to obtain further information. SELECTION CRITERIA:
      Randomised studies and cohort studies with data on clinical outcomes of RCT
      participants and similar patients who received similar treatment outside of RCTs.
      DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed
      studies for inclusion, assessed study quality and extracted data. Study authors
      were contacted for additional information. MAIN RESULTS: We included five
      randomised studies (yielding 6 comparisons) and 50 non-randomised cohort studies
      (85 comparisons), with 31,140 patients treated in RCTs and 20,380 patients
      treated outside RCTs. In the randomised studies, patients were invited to
      participate in an RCT or not; these comparisons provided limited information
      because of small sample sizes (a total of 412 patients) and the nature of the
      questions they addressed. There was statistically significant heterogeneity (P <
      0.002, I(2) = 36.2%) among the 73 dichotomous outcome comparisons; none of the
      potential explanatory factors we investigated helped to explain this
      heterogeneity. No statistically significant differences were found for 63 of the
      73 comparisons. Eight comparisons reported statistically significant better
      outcomes for patients treated within RCTs, and two comparisons reported
      statistically significant worse outcomes for patients treated within RCTs. There
      were no statistically significant differences in heterogeneity (P = 0.53, I(2) =
      0%) or in outcomes (SMD 0.01, 95% CI -0.10 to 0.12) of patients treated within
      and outside RCTs in the 18 comparisons which had used continuous outcomes.
      AUTHORS' CONCLUSIONS: This review indicates that participation in RCTs is not
      associated with greater risks than receiving the same treatment outside RCTs.
      These results challenge the assertion that the results of RCTs are not applicable
      to usual practice.

PMID- 17443631
TI  - Grey literature in meta-analyses of randomized trials of health care
      interventions.
AB  - BACKGROUND: The inclusion of grey literature (i.e. literature that has not been
      formally published) in systematic reviews may help to overcome some of the
      problems of publication bias, which can arise due to the selective availability
      of data. OBJECTIVES: To review systematically research studies, which have
      investigated the impact of grey literature in meta-analyses of randomized trials
      of health care interventions. SEARCH STRATEGY: We searched the Cochrane
      Methodology Register (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to 20
      May 2005), the Science Citation Index (June 2005) and contacted researchers who
      may have carried out relevant studies. SELECTION CRITERIA: A study was considered
      eligible for this review if it compared the effect of the inclusion and exclusion
      of grey literature on the results of a cohort of meta-analyses of randomized
      trials. DATA COLLECTION AND ANALYSIS: Data were extracted from each report
      independently by two reviewers. The main outcome measure was an estimate of the
      impact of trials from the grey literature on the pooled effect estimates of the
      meta-analyses. Information was also collected on the area of health care, the
      number of meta-analyses, the number of trials, the number of trial participants,
      the year of publication of the trials, the language and country of publication of
      the trials, the number and type of grey and published literature, and
      methodological quality. MAIN RESULTS: Five studies met the inclusion criteria.
      All five studies showed that published trials showed an overall greater treatment
      effect than grey trials. This difference was statistically significant in one of
      the five studies. Data could be combined for three of the five studies. This
      showed that, on average, published trials showed a 9% greater treatment effect
      than grey trials (ratio of odds ratios for grey versus published trials 1.09; 95%
      CI 1.03-1.16). Overall there were more published trials included in the meta
      analyses than grey trials (median 224 (IQR 108-365) versus 45(IQR 40-102)).
      Published trials had more participants on average. The most common types of grey
      literature were abstracts (55%) and unpublished data (30%). There is limited
      evidence to show whether grey trials are of poorer methodological quality than
      published trials. AUTHORS' CONCLUSIONS: This review shows that published trials
      tend to be larger and show an overall greater treatment effect than grey trials.
      This has important implications for reviewers who need to ensure they identify
      grey trials, in order to minimise the risk of introducing bias into their review.

PMID- 17443632
TI  - Time to publication for results of clinical trials.
AB  - BACKGROUND: It has been suggested that a time-lag bias exists whereby research
      studies with striking results are more likely to be stopped earlier than
      originally planned, published quicker, or both. If time-lag bias exists, new
      interventions might be mistakenly assumed to be effective. OBJECTIVES: To study
      the extent to which time to publication of a clinical trial is influenced by the
      significance of its result. SEARCH STRATEGY: Studies were identified by searching
      the Cochrane Methodology Register (The Cochrane Library, Issue 3, 2005), MEDLINE
      (1966 to May 2005), EMBASE (1980 to May 2005), Science Citation Index (June 2005)
      and by handsearching journals and conference abstracts. SELECTION CRITERIA:
      Studies were eligible if they contained analyses of any aspect of the time to
      publication of clinical trials and tracked the publication of a cohort of
      clinical trials. DATA COLLECTION AND ANALYSIS: Data extraction was performed
      independently by two authors. Data were extracted on the median time from the
      date the trial started to the date of publication. Data were also extracted on
      source of trials under investigation; source of funding; area of health care;
      means by which the publication status of these trials were sought; and
      methodological quality of the empirical study. MAIN RESULTS: Two studies with a
      total of 196 trials met the inclusion criteria. In both studies just over half of
      all trials had been published in full. Trials with positive results (i.e.
      statistically significant in favour of the experimental arm) were published in
      approximately 4 to 5 years. Trials with null or negative results (i.e. not
      statistically significant or statistically significant in favour of the control
      arm) were published after about 6 to 8 years. One study suggested that this
      difference could, in part, be attributed to the length of time taken to publish
      the results of a trial once follow up has been completed. This study showed that
      trials with null or negative findings took, on average, just over a year longer
      to be published than those with positive results. AUTHORS' CONCLUSIONS: Our
      review shows that trials with positive results are published sooner than other
      trials. This has important implications for the timing of the initiation and
      updating of a review, especially if there is an association between the inclusion
      of a trial in a review and its publication status. It is of particular concern
      when one considers reviews containing only a small number of studies.

PMID- 17443633
TI  - Randomisation to protect against selection bias in healthcare trials.
AB  - BACKGROUND: Randomised trials use the play of chance to assign participants to
      comparison groups. The unpredictability of the process, if not subverted, should
      prevent systematic differences between comparison groups (selection bias),
      provided that a sufficient number of people are randomised. OBJECTIVES: To assess
      the effects of randomisation and concealment of allocation on the results of
      healthcare trials. SEARCH STRATEGY: We searched the Cochrane Methodology
      Register, MEDLINE, SciSearch, reference lists up to August 2000 and used personal
      communication. SELECTION CRITERIA: Cohorts of trials, systematic reviews or meta
      analyses of healthcare interventions that compared outcomes or prognostic factors
      for one of the following comparisons: randomised versus non-randomised trials,
      randomised trials with adequately versus inadequately concealed allocation, or
      high versus low quality trials where selection bias could not be separated from
      other sources of bias. DATA COLLECTION AND ANALYSIS: One of us went through all
      of the citations in the Cochrane Methodology Register and accumulated reference
      lists. Studies that appeared to meet the inclusion criteria were retrieved and
      assessed independently by two of the reviewers. The methodological quality of
      included studies was appraised and information extracted by one of us and checked
      by a second. Tabular summaries of the results were prepared for each comparison
      and the results across studies were assessed qualitatively to identify common
      trends or discrepancies. MAIN RESULTS: We identified 32 studies including over
      3000 trials. Twenty-two studies compared randomised versus non-randomised trials,
      three compared adequately versus inadequately concealed allocation, and nine
      compared high versus low quality trials (some studies included more than one
      comparison). Five studies were of high methodological quality. In 15 of the 22
      studies that compared randomised and non-randomised trials of the same
      intervention, important differences were found in the estimates of effect. Some
      of these differences were due to a poorer prognosis in the control groups in the
      non-randomised trials. The results of the other seven studies that compared
      randomised and non-randomised trials across different interventions are less
      clear. Comparisons of adequately and inadequately concealed allocation in
      randomised trials of the same intervention provided high quality evidence that
      concealment can be crucial in achieving similar treatment groups and, therefore,
      unbiased estimates of treatment effects. Studies with inadequate concealment
      tended to overestimate treatment effects. Comparisons of high and low quality
      trials of the same intervention have found important differences in estimates of
      effect, but it is not possible to determine the extent to which these differences
      can be attributed to randomisation or concealment of allocation. Omitting
      comparisons between randomised trials and non-randomised trials using historical
      controls did not substantially alter the results or conclusions of our review.
      AUTHORS' CONCLUSIONS: On average, non-randomised trials and randomised trials
      with inadequate concealment of allocation tend to result in larger estimates of
      effect than randomised trials with adequately concealed allocation. However, it
      is not generally possible to predict the magnitude, or even the direction, of
      possible selection biases and consequent distortions of treatment effects.

PMID- 17443634
TI  - Strategies to improve recruitment to research studies.
AB  - BACKGROUND: Research studies are essential to improving healthcare. However, many
      fail to recruit their planned number of participants. There are many
      interventions that researchers try to improve recruitment. Finding which ones are
      effective would be of benefit to the research community and society. OBJECTIVES:
      To quantify the effects of strategies to improve participation in research
      studies. SEARCH STRATEGY: We aimed to find all randomized and quasi-randomized
      controlled trials of strategies to improve recruitment to research studies. We
      searched nine electronic databases and manually searched the reference lists of
      relevant trials. We assessed the eligibility of each trial using pre-defined
      criteria. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials
      of methods to increase recruitment in research studies. This includes non
      healthcare studies. Studies that required only questionnaire completion were
      excluded. DATA COLLECTION AND ANALYSIS: We extracted data on the method
      evaluated, nature of the population, nature of the study to be recruited into,
      randomisation or quasi-randomisation method, allocation concealment, numbers and
      proportions in each arm. We used risk ratios and their 95% confidence intervals
      to describe the effects in individual trials, and assessed heterogeneity of these
      ratios between trials. MAIN RESULTS: We identified 15 eligible trials, including
      a total of 33,719 participants. All strategies were aimed at participants for
      healthcare studies. No strategies were identified at the level of researcher
      collaborators or ethics committees. Because of heterogeneity between trials and
      within strategies, the results were not synthesised. Trials of monetary
      incentives, an additional questionnaire at invitation and treatment information
      on the consent form demonstrated benefit; these specific interventions from
      individual trials are not easily generalizable. AUTHORS' CONCLUSIONS: On this
      evidence, it is not possible to predict the effect most interventions will have
      on recruitment. Funders and researchers should ensure that the evaluation of
      recruitment strategies are incorporated into research studies.

PMID- 17443635
TI  - Editorial peer review for improving the quality of reports of biomedical studies.
AB  - BACKGROUND: Scientific findings must withstand critical review if they are to be
      accepted as valid, and editorial peer review (critique, effort to disprove) is an
      essential element of the scientific process. We review the evidence of the
      editorial peer-review process of original research studies submitted for paper or
      electronic publication in biomedical journals. OBJECTIVES: To estimate the effect
      of processes in editorial peer review. SEARCH STRATEGY: The following databases
      were searched to June 2004: CINAHL, Ovid, Cochrane Methodology Register,
      Dissertation abstracts, EMBASE, Evidence Based Medicine Reviews: ACP Journal
      Club, MEDLINE, PsycINFO, PubMed. SELECTION CRITERIA: We included prospective or
      retrospective comparative studies with two or more comparison groups, generated
      by random or other appropriate methods, and reporting original research,
      regardless of publication status. We hoped to find studies identifying good
      submissions on the basis of: importance of the topic dealt with, relevance of the
      topic to the journal, usefulness of the topic, soundness of methods, soundness of
      ethics, completeness and accuracy of reporting. DATA COLLECTION AND ANALYSIS:
      Because of the diversity of study questions, viewpoints, methods, and outcomes,
      we carried out a descriptive review of included studies grouping them by broad
      study question. MAIN RESULTS: We included 28 studies. We found no clear-cut
      evidence of effect of the well-researched practice of reviewer and/or author
      concealment on the outcome of the quality assessment process (9 studies).
      Checklists and other standardisation media have some evidence to support their
      use (2 studies). There is no evidence that referees' training has any effect on
      the quality of the outcome (1 study). Different methods of communicating with
      reviewers and means of dissemination do not appear to have an effect on quality
      (3 studies). On the basis of one study, little can be said about the ability of
      the peer-review process to detect bias against unconventional drugs. Validity of
      peer review was tested by only one small study in a specialist area. Editorial
      peer review appears to make papers more readable and improve the general quality
      of reporting (2 studies), but the evidence for this has very limited
      generalisability. AUTHORS' CONCLUSIONS: At present, little empirical evidence is
      available to support the use of editorial peer review as a mechanism to ensure
      quality of biomedical research. However, the methodological problems in studying
      peer review are many and complex. At present, the absence of evidence on efficacy
      and effectiveness cannot be interpreted as evidence of their absence. A large,
      well-funded programme of research on the effects of editorial peer review should
      be urgently launched.

PMID- 17443636
TI  - Incentives and disincentives to participation by clinicians in randomised
      controlled trials.
AB  - BACKGROUND: Patients and clinicians need reliable, up-to-date information from
      randomised controlled trials (RCTs) on the costs and benefits of treatments.
      Recruitment difficulties arise when clinicians do not invite patients to
      participate in trials. OBJECTIVES: Primary: to assess the evidence for the effect
      of disincentives and incentives on the extent to which clinicians invite eligible
      patients to participate in RCTs of healthcare interventions. Secondary: to assess
      the evidence in relation to stated willingness to invite participation. SEARCH
      STRATEGY: 1. The Cochrane Methodology Register and Cochrane Database of
      Methodology Reviews were searched in May 2006 and Cochrane Central Register of
      Controlled Trials, National Research Register and ClinicalTrialsGov in April
      2005.2. EMBASE, MEDLINE, CINAHL, PsycINFO and AMED were searched in April 2005.3.
      Reference lists of included studies were checked. SELECTION CRITERIA: Studies
      exploring the effect of (dis)incentives on clinicians' views and recruitment
      related activity. DATA COLLECTION AND ANALYSIS: The information about included
      studies was insufficient for a full assessment of quality. Data on
      (dis)incentives were extracted and association with recruitment tested. MAIN
      RESULTS: No RCTs of interventions were identified. Eleven observational studies
      were included - two medical records reviews, one matched pair study, one
      clinician interview study, two studies documenting clinicians' decisions and five
      postal surveys. Three measures of recruitment were used, invitation to
      participate, entry into RCT and reported entry to RCT. Five studies explored the
      effect of patient characteristics. The effect of age and prognosis varied between
      trials. Six studies considered the association between clinicians' views and
      recruitment. Clinicians who agreed to participate because they were acquainted
      with the researchers were less likely to participate than those otherwise
      motivated (1 study, 2-sided p = 0.04 Fisher's exact test) and (Odds Ratio [OR]
      0.4, 95% Confidence Interval [CI] 0.2 to 0.9, 1 study). Clinicians who had
      recruited were more likely to report some difficulties including "trials involve
      extra work" (OR 92.94, 95% CI 4.54 - 1902.11; p </= 0.01, 1 study) and "inviting
      patients to participate is embarrassing" (chi-square 15.55, df = 1, p < 0.0001, 1
      study). The effect of the need to discuss clinical uncertainty was unclear but
      concern that the doctor-patient relationship would be adversely affected by
      participation was a deterrent (chi-square = 7.25, df = 1, p = 0.007, 1 study).
      AUTHORS' CONCLUSIONS: The impact of factors varied across studies. Researchers
      need to be aware that aspects of the design and conduct of trials can affect
      clinicians' willingness to invite patients to participate. Further research is
      needed.

PMID- 17443640
TI  - Comparative proteomic analysis of human pancreatic juice: methodological study.
AB  - Pancreatic cancer is the most lethal of all the common malignancies. Markers for
      early detection of this disease are urgently needed. Here, we optimized and
      applied a proteome analysis of human pancreatic juice to identify biomarkers for
      pancreatic cancer. Pancreatic juice samples, devoid of blood or bile
      contamination, were collected from patients with pancreatic cancer (n = 5),
      benign pancreatic diseases (n = 6), or cholelithiasis (n = 3) during endoscopic
      retrograde cholangiopancreatography (ERCP). After ultramembrane centrifugation
      sample preparation, pancreatic juice proteins were separated by 2-DE and
      identified by MALDI-TOF-MS. A 2-DE dataset of pancreatic juice from patients with
      cholelithiasis was established, consisting of 76 protein spots representing 22
      different proteins. Disease-associated obstruction of the pancreatic duct
      strongly effected the protein composition of pancreatic juice. Concurrently,
      pancreatic juice from patients with pancreatic cancer was compared to
      nonmalignant controls with comparable obstruction of pancreatic ducts. Seven
      protein spots were identified that consistently appeared at changed levels in
      pancreatic juice from patients with pancreatic cancer. In conclusion, comparative
      proteomic analysis of human pancreatic juice can be used to identify biomarkers
      of pancreatic cancer.

PMID- 17443642
TI  - Implications of 15N-metabolic labeling for automated peptide identification in
      Arabidopsis thaliana.
AB  - We report the first metabolic labeling of Arabidopsis thaliana for proteomic
      investigation, demonstrating efficient and complete labeling of intact plants.
      Using a reversed-database strategy, we evaluate the performance of the MASCOT
      search engine in the analysis of combined natural abundance and 15N-labeled
      samples. We find that 15N-metabolic labeling appears to increase the ambiguity
      associated with peptide identifications due in part to changes in the number of
      isobaric amino acids when the isotopic label is introduced. This is reflected by
      changes in the distributions of false positive identifications with respect to
      MASCOT score. However, by determining the nitrogen count from each pair of
      labeled and unlabeled peptides we may improve our confidence in both heavy and
      light identifications.

PMID- 17443643
TI  - Modeling the proteome of a Marek's disease transformed cell line: a natural
      animal model for CD30 overexpressing lymphomas.
AB  - Marek's disease (MD) in the chicken, caused by the highly infectious MD alpha
      herpesvirus (MDV), is both commercially important and a unique, naturally
      occurring model for human T-cell lymphomas overexpressing the Hodgkin's disease
      antigen, CD30. Here, we used proteomics as a basis for modeling the molecular
      functions and biological processes involved in MDV-induced lymphomagenesis.
      Proteins were extracted from an MDV-transformed cell line and were then
      identified using 2-D LC-ESI-MS/MS. From the resulting 3870 cellular and 21 MDV
      proteins we confirm the existence of 3150 "predicted" and 12 "hypothetical"
      chicken proteins. The UA-01 proteome is proliferative, differentiated,
      angiogenic, pro-metastatic and pro-immune-escape but anti-programmed cell death, 
      anergy, -quiescence and -senescence and is consistent with a cancer phenotype. In
      particular, the pro-metastatic integrin signaling pathway and the ERK/MAPK
      signaling pathways were the two predominant signaling pathways represented. The
      cytokines, cytokine receptors, and their related proteins suggest that UA-01 has
      a regulatory T-cell phenotype.

PMID- 17443644
TI  - Factors of complicated grief pre-death in caregivers of cancer patients.
AB  - PURPOSE: Over the past decade, Prigerson and her colleagues have shown that
      symptoms of 'complicated grief'-intense yearning, difficulty accepting the death,
      excessive bitterness, numbness, emptiness, and feeling uneasy moving on and that
      the future is bleak-are distinct from depression and anxiety and are
      independently associated with substantial morbidity. Little is known about
      complicated grief experienced by family caregivers prior to the death. This study
      sought to examine differences in caregiver age groups and potential risk factors
      for complicated grief pre-death. METHOD: Two hundred and forty eight caregivers
      from multiple sites nationwide (20-86 years of age) identified themselves as
      primary caregivers to a terminally ill cancer patient. Each caregiver was
      interviewed using the following measures: the Pre-Death Inventory of Complicated
      Grief-Caregiver Version; the Brief Interpersonal Support Evaluation List; the
      Structured Clinical Interview for the DSM-IV Axis I; the Life Orientation Test
      Revised; the SEPRATE Measure of Stressful Life Events; the Covinsky Family Impact
      Survey; and mental health access questions. RESULTS: The study found that those
      under 60 years old had higher levels of complicated grief pre-death than
      caregivers 60 and older (t(246) = 2.30, p < 0.05). Significant correlations were
      also found between levels of complicated grief pre-loss and the following
      psychosocial factors: perceived social support (r = -0.415, p < 0.001); history
      of depression (r = -0.169, p < 0.05); current depression (r = -0.158, p < 0.05);
      current annual income (Spearman rho = -0.210, p < 0.01); annual income at time of
      patient's diagnosis (Spearman rho = -0.155, p = 0.05); pessimistic thinking (r =
      0.320, p < 0.001); and number of moderate to severe stressful life events
      (Spearman rho = 0.218, p = 0.001). In a multi-variate analysis (R(2) = 0.368),
      pessimistic thinking (Beta = 0.208, p < 0.05) and severity of stressful life
      events (Beta = 0.222, p < 0.05) remained as important factors to developing
      complicated grief pre-death. CONCLUSIONS: These results suggest that mental
      health professionals who work with caregivers should pay particular attention to
      pessimistic thinking and stressful life events, beyond the stress of the loved
      one's illness, that caretakers experience. Additionally, although not reaching
      significance, mental health professionals should also consider younger caregivers
      at greater risk for complicated grief pre-loss.

PMID- 17443645
TI  - Prospective study of depression and fatigue in men with advanced prostate cancer
      receiving hormone therapy.
AB  - PURPOSE: We prospectively examined the development of depressive symptoms and
      fatigue among men with locally advanced prostate cancer receiving hormone
      therapy. METHODS: Fifty-two men with advanced or recurrent prostate cancer were
      randomly assigned to receive either parenteral leuprolide or oral bicalutamide.
      Patients completed the Beck Depression Inventory (BDI) and Fatigue Severity Scale
      (FSS) at pretreatment baseline, 6 months, and 12 months. RESULTS: Rates of at
      least mild depression ranged from 10.4 to 16.3% over the 12 months and were not
      significantly different at each time point. Mean change in BDI scores from
      baseline to 6 months for the entire sample was 0.91 (SE = 0.73), and from
      baseline to 12 months was 0.35 (SE = 0.67). Mean FSS scores increased
      significantly from baseline (M = 24.43, SD = 11.75) to 6 months (M = 27.93, SD =
      13.52) and remained steady at 12 months (M = 27.80, SD = 14.44). There were no
      significant differences in depression between the two types of hormone therapy.
      CONCLUSION: Hormone therapy does not appear to cause clinically significant
      changes in depression among men with locally advanced prostate cancer. However,
      fatigue increased significantly over the study period.

PMID- 17443646
TI  - Effect of gender on the pharmacokinetics of eslicarbazepine acetate (BIA 2-093),
      a new voltage-gated sodium channel blocker.
AB  - PURPOSE: To determine the effect of gender on the pharmacokinetics of
      eslicarbazepine acetate, a novel voltage-gated sodium channel blocker in the
      development for the treatment of epilepsy and bipolar disorder. METHODS: Single
      centre, open-label, parallel-group study in 12 female and 12 male healthy
      subjects. The study consisted of a single-dose (600 mg) period and a multiple
      dose (600 mg, once-daily, for 8 days) period, separated by 4 days. RESULTS:
      Eslicarbazepine acetate was rapidly and extensively metabolized to
      eslicarbazepine (S-licarbazepine), the main active metabolite. Following a single
      dose, arithmetic mean eslicarbazepine maximum plasma concentrations (C(max)) and
      area under the plasma concentration-time curve over 24 h (AUC(0-24)) and from 0
      to infinity (AUC(0-infinity)) were, respectively, 9.3 microg/ml, 128.5 microg
      h/ml and 171.9 microg h/ml in male subjects and 10.1 microg/ml, 150.1 microg h/ml
      and 205.0 microg h/ml in female subjects. At steady-state, C(max), AUC(0-24) and
      AUC(0-infinity) were 15.5 microg/ml, 207.8 microg h/ml and 295.8 microg h/ml in
      male subjects, and 16.8 microg/ml, 214.5 microg h/ml and 295.2 microg h/ml in
      female subjects. Steady-state plasma concentrations were attained at 4 to 5 days
      of administration in both groups. Eslicarbazepine C(max), AUC(0-24) and AUC(0
      infinity) female:male geometric mean ratios (90%CI) were, respectively, 1.09
      (0.94; 1.24), 1.16 (1.00; 1.33) and 1.17 (0.99; 1.38) following single-dose, and
      1.10 (0.97; 1.25), 1.04 (0.92; 1.17) and 1.01 (0.88; 1.16) at steady-state.
      CONCLUSION: At steady-state, the pharmacokinetic profile of eslicarbazepine
      acetate was not affected by gender.

PMID- 17443647
TI  - In vitro LC-MS cocktail assays to simultaneously determine human cytochrome P450
      activities.
AB  - Using liquid chromatography-mass spectrometry (LC-MS), two sensitive cocktail
      assays were developed, one to simultaneously determine activities of the
      cytochrome P450 enzymes, CYP1A2 (phenacitin), 2B6 (bupropion), 2C8 (amodiaquine)
      and 2C19 (omperazole), and the other to determine simultaneously activities of
      CYP3A4/5 (testosterone), 2C9 (tolbutamide) and 2D6 (dextromethorphan). These
      cocktail assays are sensitive, require only a small amount of microsomal protein,
      employ selective and high turnover CYP substrates and do not require post
      incubation extraction. In each of these cocktails, no interactions were observed
      between the substrates. Combining the two cocktails into a single cocktail
      resulted in significant inhibition of CYP2D6 by amiodiaquine. These assays were
      used successfully to determine induction of CYP enzymes in microsomes isolated
      from human hepatocytes treated (72 h) with or without the prototypic inducer,
      rifampin.

PMID- 17443648
TI  - Isolated noncompaction of the ventricular myocardium: contemporary diagnosis and
      management.
AB  - Noncompaction of the ventricular myocardium is a rare form of cardiomyopathy that
      has been described since the early 1990s. However, noncompaction remains
      frequently overlooked, in part due to the limited awareness of its unique
      clinical and imaging characteristics. Contemporary diagnosis has been facilitated
      by the introduction of specific morphologic criteria by echocardiography and
      cardiac magnetic resonance. Management issues revolve around the management of
      heart failure, arrhythmias, and thromboembolic events in order to prevent the
      significant morbidity and even mortality that has been associated with this
      entity. Finally, the genetics of noncompaction have been diverse and an issue of
      clinical importance as it relates to screening of first-degree relatives of
      affected patients. Two recent cases are presented and many of the contemporary
      issues in diagnosis and management, based on an extensive review of the
      literature, are addressed.

PMID- 17443649
TI  - Systemic nanoparticle paclitaxel (nab-paclitaxel) for in-stent restenosis I
      (SNAPIST-I): a first-in-human safety and dose-finding study.
AB  - BACKGROUND: Paclitaxel-eluting stents inhibit restenosis; however, this
      technology has drawbacks (e.g., stent thrombosis, requirement for long-term
      antiplatelet therapy, and cost--particularly for patients with multivessel
      disease). Systemic treatment with a novel 130-nm, albumin-bound particle form of
      paclitaxel (nab-paclitaxel) has been shown to reduce restenosis in animals.
      HYPOTHESIS: This study was designed to establish the safety and optimal dose of
      systemic nab-paclitaxel for reducing in-stent restenosis in humans. If well
      tolerated, systemic nab-paclitaxel may be used with any available bare-metal
      stent and at potentially lower cost than drug-eluting stents. METHODS: Patients
      received nab-paclitaxel 10, 30, 70, or 100 mg/m(2) intravenously after stenting
      of a single de novo lesion >or= 3 mm in diameter. Study endpoints included safety
      and major adverse cardiac events (MACE) at 2 and 6 months. RESULTS: Data were
      obtained for all 23 enrolled patients (mean age 66 +/- 10 years, 74% men, 26%
      with diabetes). No significant adverse events (AE) were attributable to nab
      paclitaxel at 10 or 30 mg/m(2). Moderate neutropenia, moderate sensory
      neuropathy, and mild to moderate, reversible alopecia occurred only at doses of
      70 and 100 mg/m(2); therefore, doses of 70 mg/m(2) or higher were considered
      unacceptable in this patient population. No MACE were reported at 2 months. At 6
      months, 4 target lesion revascularizations (TLR) for restenoses were reported (2
      each in the 10- and 100-mg/m(2)-dose groups). CONCLUSIONS: Systemic nab
      paclitaxel was well tolerated at doses below 70 mg/m(2) in this group of
      patients; no unexpected AE were noted. Additional studies are under way to
      explore intravenous and intracoronary administration of nab-paclitaxel.

PMID- 17443650
TI  - Clinical characteristics and outcomes of hypertrophic cardiomyopathy in Taiwan--a
      tertiary center experience.
AB  - BACKGROUND: Most information concerning hypertrophic cardiomyopathy has been
      derived from western countries and Japan. HYPOTHESIS: Patients with hypertrophic
      cardiomyopathy in Taiwan may have a distinct morphology and clinical picture.
      METHODS: Information from 163 consecutive patients with hypertrophic
      cardiomyopathy at a medical center in Taiwan from 1990 through 2005 was
      retrospectively collected. The diagnosis of hypertrophic cardiomyopathy required
      echocardiographic demonstration of left ventricular hypertrophy (wall thickness
      >or= mm during diastole) in a specific region or with diffuse distribution.
      Follow-up information was obtained from medical records. RESULTS: Among 163
      patients (male, 52%), the mean follow-up period was 5.3 +/- 4.1 years. Men had
      nearly a threefold increase in prevalence of apical hypertrophic cardiomyopathy
      (23.8% vs. 8.9%, p = 0.03), younger onset of initial evaluation (57.2 +/- 12.9
      vs. 64.8 +/- 11.3, p < 0.001), and lower prevalence of hypertrophic obstructive
      cardiomyopathy (33.3% vs. 63.3%, p < 0.001) compared to women. Fifty-eight
      patients (35.6%) experienced cardiovascular events, of which pulmonary edema and
      paroxysmal atrial fibrillation were the most common (19.7% and 12.3%,
      respectively). The annual cardiovascular mortality rate was 0.8%. In multivariate
      analysis, left ventricular outflow obstruction [odds ratio (OR): 4.92, p =
      0.001], atrial fibrillation (OR: 3.53, p = 0.014), and female gender (OR: 2.99, p
      = 0.043) were independent predictors of mortality. CONCLUSIONS: Hypertrophic
      cardiomyopathy did not significantly increase cardiovascular mortality rate, but
      over one-third of patients with hypertrophic cardiomyopathy experienced
      cardiovascular events. High prevalence of left ventricular outflow obstruction
      especially in elderly women was observed. Left ventricular outflow obstruction,
      atrial fibrillation, and female gender were predictors of mortality.

PMID- 17443651
TI  - Implantation of a biventricular ICD system in a patient with a persistent left
      superior vena cava.

PMID- 17443652
TI  - Henry J. L. Marriott: lucid teacher of electrocardiography.

PMID- 17443653
TI  - Metabolic syndrome in African Americans: implications for preventing coronary
      heart disease.
AB  - The metabolic syndrome represents a specific clustering of cardiovascular risk
      factors in the same individual (abdominal obesity, atherogenic dyslipidemia,
      elevated blood pressure, insulin resistance, a prothrombotic state, and a
      proinflammatory state). Almost 50 million American adults (about one in four)
      have the metabolic syndrome, which puts them at increased risk for the
      development of diabetes mellitus and cardiovascular disease. African Americans,
      especially African-American women, have a high prevalence of the metabolic
      syndrome. This is attributable mainly to the disproportionate occurrence in
      African Americans of elevated blood pressure, obesity, and diabetes. Management
      of the metabolic syndrome consists primarily of modification or reversal of the
      root causes (overweight/obesity and physical inactivity) and therapy to reduce or
      control the risk factors. Although all components of the metabolic syndrome
      should be addressed, optimal control of atherogenic dyslipidemia and elevated
      blood pressure may reduce cardiovascular risk by more than 80%.

PMID- 17443654
TI  - Cardiac manifestations of parasitic infections part 1: overview and
      immunopathogenesis.
AB  - Parasitic infections produce a wide spectrum of cardiac manifestations. They may
      involve various anatomic structures of the heart and are manifested clinically as
      myocarditis, cardiomyopathies, pericarditis, or pulmonary hypertension in many
      resource-constrained settings. However, many parasitic infections involving the
      heart may also be currently diagnosed in developed countries due to growing
      worldwide travel, blood transfusions, and increasing numbers of immunosuppression
      states such as organ transplantation, use of immunosuppressive agents, or
      HIV/AIDS. Clinicians anywhere in the globe need to be aware of the potential
      cardiac manifestations of parasitic diseases. This is part one of a three-part
      series discussing parasites of the heart. In this section, we provide a general
      overview and immunopathogenesis of parasitic infections of the heart.

PMID- 17443655
TI  - A case report of simultaneous thrombosis of two coronary artery stents in
      association with clopidogrel resistance.
AB  - Despite aggressive antiplatelet therapy in the setting of PCI, the incidence of
      acute stent thrombosis remains approximately 0.5-2%. We report a patient with
      simultaneous thrombosis of two drug-eluting coronary artery stents, suggesting a
      systemic thrombotic state. Evaluation by optical platelet aggregometry revealed
      clopidogrel resistance, which was overcome at a higher drug dose. We aim to
      highlight the potential utility of platelet function analysis to guide therapy
      for patients in whom inadequate antiplatelet therapy may have catastrophic
      clinical outcomes.

PMID- 17443656
TI  - Heparin anticoagulation.

PMID- 17443657
TI  - Aortic vegetation and aortic dissection in the same echocardiographic frame.

PMID- 17443658
TI  - A risk-predictive score for cardiogenic shock after acute myocardial infarction
      in Chinese patients.
AB  - BACKGROUND: Cardiogenic shock after acute myocardial infarction (AMI) remains a
      poor prognosis. Although numerous studies discussed the predictors of cardiogenic
      shock complicating AMI, the data in Chinese patients is still absent. The goal of
      this study is to develop a risk-predictive score for cardiogenic shock after AMI,
      among Chinese patients, so as to guide clinicians to prevent cardiogenic shock.
      METHODS: Patients with ST-segment elevated AMI were provided by two Chinese
      hospitals from 1994 to 2004. Baseline characteristics of each case were
      documented. Multivariable logistic regression modeling techniques were used to
      develop a model to predict the occurrence of cardiogenic shock within 72 h after
      admission. On the basis of the coefficients in the model, a risk score was
      developed for the probability of cardiogenic shock. To test its viability,
      another population, which was consistent with the original population, confirmed
      the scoring. RESULTS: Among 2,077 patients, 184 cases developed cardiogenic shock
      within 72 h. Age, gender, BMI, killip class, MI location, multivessel disease,
      previous MI, family history of CAD, and thrombolytic therapy were strong
      predictors for shock after AMI. A risk-predictive score for shock was developed.
      It predicted cardiogenic shock accurately in another Chinese population.
      CONCLUSIONS: A predictive model is developed in Chinese patients with AMI for the
      first time. It is based on some simple parameters, which can be easily obtained
      by clinicians. The risk score derived from the model can predict cardiogenic
      shock accurately.

PMID- 17443659
TI  - Prognostic value of the computerized ECG in Hispanics.
AB  - BACKGROUND: The prevalence and prognostic values of electrocardiogram (ECG)
      abnormalities in Hispanics have not been compared to other ethnicities in a large
      population. Despite a worse cardiovascular risk profile, the prevalence of
      cardiovascular disease is lower in Hispanics compared to non-Hispanics.
      HYPOTHESIS: We hypothesized that ECG abnormalities were less common in Hispanics
      and were not as strongly associated with cardiovascular mortality. METHODS:
      45,563 ECGs ordered for usual clinical indications in a Veteran's hospital were
      available for analysis. 1,392 patients who died within one week of the ECG were
      excluded. Demographic characteristics were recorded and the population was
      followed for an average of 7.5 years using the California Death Index. The
      presence of baseline ECG characteristics were recorded and analyzed using the
      GE/Marquette computerized ECG system. Age, sex and heart rate adjusted Cox hazard
      ratio analyses were performed. RESULTS: Being Hispanic was associated with lower
      cardiovascular death, with a hazard ratio (HR) of 0.76 (95% CI 0.65-0.89).
      Findings such as atrial fibrillation, presence of Q-waves, left ventricular
      hypertrophy (LVH), upright T-waves in aortic valve replacement (aVR) and cardiac
      Infarction Injury Scores > 6 were significantly less prevalent in Hispanics than
      in non-Hispanics. These findings were similarly associated with increased
      cardiovascular mortality in both groups, each with a HR of approximately 2.
      CONCLUSION: The lower prevalence of ECG characteristics associated with coronary
      heart disease, atrial fibrillation and left ventricular hypertrophy support prior
      observations that cardiovascular disease is less prevalent in the Hispanic
      population. These findings, however, are similarly associated with increased
      mortality compared to non-Hispanics.

PMID- 17443660
TI  - The prevalence of prehypertension and hypertension among rural adults in Liaoning
      province of China.
AB  - BACKGROUND: The objective of this study was to estimate the prevalence of
      prehypertension and hypertension in the rural adults of Liaoning province of
      China. METHODS: The study was conducted in 2004-2006, using a multistage cluster
      sampling method to select a representative sample. A total of 45925 adults, 35
      years or older, were examined. Two blood pressure measurements were obtained by
      trained observers by use of a standardized electric sphygmomanometer after a 5
      min sitting rest. Information on the history of hypertension was obtained by use
      of a standard questionnaire. RESULTS: Overall, the prevalence of prehypertension
      was 44.1%; for men 48.7 and women 39.6%. The prevalence of hypertension was
      37.8%; for men 37.0 and women 38.6%. Among hypertensive patients, only 29.5%
      patients were aware of their high blood pressure, 23.6% patients were taking
      antihypertensive medication, and 1.1% patients achieved blood pressure control.
      CONCLUSIONS: Prehypertension and hypertension are highly prevalent in rural areas
      of China. The percentage of those with hypertension who are aware, treated, and
      controlled are unacceptably low. These results underscore the urgent need to
      develop strategies to improve prevention, detection, and treatment of
      hypertension in rural areas of China.

PMID- 17443661
TI  - The PAH gene, phenylketonuria, and a paradigm shift.
AB  - "Inborn errors of metabolism," first recognized 100 years ago by Garrod, were
      seen as transforming evidence for chemical and biological individuality.
      Phenylketonuria (PKU), a Mendelian autosomal recessive phenotype, was identified
      in 1934 by Asbjorn Folling. It is a disease with impaired postnatal cognitive
      development resulting from a neurotoxic effect of hyperphenylalaninemia (HPA).
      Its metabolic phenotype is accountable to multifactorial origins both in nurture,
      where the normal nutritional experience introduces L-phenylalanine, and in
      nature, where mutations (>500 alleles) occur in the phenylalanine hydroxylase
      gene (PAH) on chromosome 12q23.2 encoding the L-phenylalanine hydroxylase enzyme
      (EC 1.14.16.1). The PAH enzyme converts phenylalanine to tyrosine in the presence
      of molecular oxygen and catalytic amounts of tetrahydrobiopterin (BH4), its
      nonprotein cofactor. PKU is among the first of the human genetic diseases to
      enter, through newborn screening, the domain of public health, and to show a
      treatment effect. This effect caused a paradigm shift in attitudes about genetic
      disease. The PKU story contains many messages, including: a framework on which to
      appreciate the complexity of PKU in which phenotype reflects both locus-specific
      and genomic components; what the human PAH gene tells us about human population
      genetics and evolution of modern humans; and how our interest in PKU is served by
      a locus-specific mutation database (http://www.pahdb.mcgill.ca; last accessed 20
      March 2007). The individual Mendelian PKU phenotype has no "simple" or single
      explanation; every patient has her/his own complex PKU phenotype and will be
      treated accordingly. Knowledge about PKU reveals genomic components of both
      disease and health.

PMID- 17443662
TI  - Axonal degeneration in the Trembler-j mouse demonstrated by stimulated single
      fiber electromyography.
AB  - The Trembler-j (Tr-j) mouse is a naturally occurring mutant with a point mutation
      in the peripheral myelin protein-22 gene causing severe peripheral nerve
      demyelination. It is a genetically homologous murine model for Charcot-Marie
      Tooth disease type 1A (CMT 1A). Our prior pilot studies using stimulated single
      fiber needle electromyograpy (SSFEMG) showed increased jitter in 60-day-old Tr-j
      mice compared to age-matched, wildtype animals. The aim of this study was to
      better elucidate the etiology of increased jitter in Tr-j mice and test the
      following hypotheses: (1) the increased jitter in Tr-j mice is due to turnover of
      endplates secondary to axonal degeneration with reinnervation and not to
      conduction block secondary to demyelination of motor nerve axons; and (2) aging
      Tr-j mice demonstrate increased jitter and fiber density compared with younger
      mutant mice due to progressive motor axon loss. SSFEMG studies performed on 60-
      and 140-day-old mice indicated that average mean consecutive difference (MCD) and
      fiber density estimates (FDE) were significantly increased in Tr-j mice at both
      ages compared to age-matched wildtypes. FDE also increased substantially in older
      mutant mice. Intraperitoneal neostigmine injections produced significant
      reductions in average MCD in Tr-j mice, suggesting that impaired neuromuscular
      transmission is an early pathologic feature in these mice and likely reflects
      distal axonal degeneration. Our findings corroborate our prior pilot study,
      although in a much larger number of animals across a wider age span. Our study
      also indicates that SSFEMG, performed in a serial fashion, is a useful,
      noninvasive method of detecting progressive axon loss in this murine model of CMT
      1A. This technique may be a valuable tool to study the affects of genetic or
      pharmaceutical interventions in murine models of peripheral neuropathy. Muscle
      Nerve, 2007.

PMID- 17443663
TI  - Magnetic stimulation including the triple-stimulation technique in amyotrophic
      lateral sclerosis.
AB  - To study the relative importance of upper motor neuron (UMN) dysfunction in the
      weakness of amyotrophic lateral sclerosis (ALS) and to compare the sensitivity of
      several transcranial magnetic stimulation (TMS) parameters as means of assessing
      UMN impairment in ALS, we used TMS to evaluate one upper limb of 63 patients. The
      triple-stimulation technique (TST) and silent period (SP) were found to be the
      most frequently abnormal parameters (55.6% and 47.6%, respectively), without
      significant difference in their diagnostic sensitivity. The SP was found to be a
      useful parameter in patients with suspected or possible ALS. A positive
      correlation was found between weakness and the TST amplitude ratio, indicating
      that weakness may partly be caused by UMN dysfunction. Thus, the TST provides a
      quantitative tool for assessing UMN conduction failure. When used in association
      with the SP, the TST provides a sensitive diagnostic tool for use on ALS
      patients.

PMID- 17443664
TI  - Ethnic variation in return to baseline values of patient-reported outcomes in
      older prostate cancer patients.
AB  - BACKGROUND: Ethnic variation in patient-reported outcomes such as health-related
      quality of life (HRQoL) and satisfaction with care are understudied areas in the
      management of elderly prostate cancer (PCa) patients. METHODS: In this
      prospective cohort study, between the years 2002 and 2004, the authors recruited
      214 older (>or=65 years) men with newly diagnosed PCa from an urban academic
      hospital and a Veterans Administration hospital. Participants completed generic
      (SF-36), prostate-specific (UCLA-PCI) HRQoL, and satisfaction with care (CSQ-8)
      surveys at baseline and at 3, 6, and 12-months follow-up. Clinically significant
      difference was used to compute return to baseline. The authors compared time to
      return to baseline HRQoL after controlling for confounding variables by using
      ANOVA and log-linear models. Survival curves were used to compare time to return
      to baseline across ethnicity. RESULTS: Regression analysis revealed that age and
      marital status, not ethnicity, were independent predictors of radical
      prostatectomy, rather than radiation treatment. African Americans reported lower
      HRQoL scores at diagnosis and required a longer time to return to baseline. Log
      linear analysis indicated that African-American ethnicity was associated with
      lower 12-month scores for role physical (odds ratio [OR], 0.46; standard error
      [SE], 0.40), role emotional (OR, 0.37; SE, 0.43), bodily pain (OR, 0.74; SE,
      0.10), urinary function (OR, 0.90; SE, 0.11), and urinary bother (OR, 0.72; SE,
      0.17). Both groups reported comparably high levels of satisfaction with care.
      CONCLUSIONS: African-American elderly exhibited poorer outcomes and required a
      longer time to return to baseline HRQoL. These differences highlight the need for
      discussion with patients and families prior to treatment about expectations and
      the need for support services post-treatment.

PMID- 17443665
TI  - Fak/Src signaling in human intestinal epithelial cell survival and anoikis:
      differentiation state-specific uncoupling with the PI3-K/Akt-1 and MEK/Erk
      pathways.
AB  - Human intestinal epithelial cell survival and anoikis are distinctively regulated
      according to the state of differentiation. In the present study, we analyzed the
      roles of focal adhesion kinase (Fak)/Src signaling to the PI3-K/Akt-1 and mitogen
      activated protein kinase (MEK)/extracellular regulated kinases (Erk) pathways,
      within the context of such differentiation-state distinctions. Anoikis was
      induced by inhibition of beta1 integrins (antibody blocking), inhibition of Fak
      (pharmacologic inhibition or overexpression of dominant negative mutants), or by
      maintaining cells in suspension. Activation parameters of Fak, Src, Akt-1, and
      Erk1/2 were analyzed. Activities of Src, Akt-1, or Erk1/2 were also blocked by
      pharmacological inhibition or by overexpression of dominant-negative mutants. We
      report that: (1) the loss or inhibition of beta1 integrin binding activity causes
      anoikis and results in a down-activation of Fak, Src, Akt-1, and Erk1/2 in both
      undifferentiated, and differentiated cells; (2) the inhibition of Fak likewise
      causes anoikis and a down-activation of Src, Akt-1, and Erk1/2, regardless of the
      differentiation state; (3) Src, PI3-K/Akt-1, and MEK/Erk contribute to the
      survival of differentiated cells, whereas MEK/Erk does not play a role in the
      survival of undifferentiated ones; (4) the inhibition/loss of beta1 integrin
      binding and/or Fak activity results in a loss of Src engagement with Fak,
      regardless of the state of differentiation; and (5) Src contributes to the
      activation of both the PI3-K/Akt-1 and MEK/Erk pathways in undifferentiated
      cells, but does not influence PI3-K/Akt-1 in differentiated ones. Hence, Fak/Src
      signaling to the PI3-K/Akt-1 and MEK/Erk pathways undergoes a differentiation
      state-specific uncoupling which ultimately reflects upon the selective engagement
      of these same pathways in the mediation of intestinal epithelial cell survival.

PMID- 17443666
TI  - Effects of combinations of ROS scavengers on oxidative DNA damage caused by
      visible-light-activated camphorquinone/N,N-dimethyl-p-toluidine.
AB  - The objective of this investigation was to analyze whether various combinations
      of the ROS scavengers glutathione (GSH), N-acetyl-cysteine (NAC), and vitamins C
      and E decrease DNA damage due to visible-light-irradiated (VL-irradiated)
      camphorquinone/N,N-dimethyl-p-toluidine (CQ/DMT) compared with individual vitamin
      C or E. PhiX-174 RF plasmid DNA was used to determine single and double strand
      breaks as parameters of DNA damage. Individual ROS scavengers and combinations of
      the antioxidants were added to plasmid DNA treated with VL-irradiated CQ/DMT/Cu
      (II). After incubation, DNA was loaded into a 1% agarose gel. Following
      electrophoresis, gels stained with 0.5 microg/mL ethidium bromide were
      photographed under ultraviolet illumination and analyzed with NIH ImageJ
      software. Results were evaluated between groups for statistical significance
      using Student's paired t-test (p < 0.05). Glutathione significantly reduced
      oxidative DNA damage at all test concentrations when combined with vitamin C or
      vitamin E. The concentration of damaged DNA observed in the presence of
      combinations of GSH with vitamin C or vitamin E was significantly lower compared
      with all other combinations of antioxidants investigated in our study (p < 0.05).
      In contrast to GSH, NAC was not able to compensate the pro-oxidative effects of
      vitamin C and vitamin E. Only at a concentration of 2 mM, NAC combined with
      vitamin C efficiently prevented CQ/DMT/Cu (II)-associated DNA damage. Our data
      indicate that solely the combinations of GSH with vitamin C or vitamin E
      significantly reduce the severity of oxidative DNA damage caused by CQ/DMT,
      whereas NAC may even increase the pro-oxidant activity of vitamin C and vitamin
      E.

PMID- 17443667
TI  - Calcium sulfate-carboxymethylcellulose bone graft binder: Histologic and
      morphometric evaluation in a critical size defect.
AB  - Calcium sulfate (CS) is widely used as a bone graft binder and expander. Recent
      reports indicate that carboxymethylcellulose (CMC) can improve the clinical
      properties of CS when used as binder for particulate bone grafts; however,
      limited information is available on the effects of CMC on bone regeneration. The
      purpose of this study was to evaluate the histologic and morphometric
      characteristics of bone formation in calvarial defects grafted with a CS-based
      putty containing 10% CMC in combination with allogeneic demineralized bone matrix
      (DBM). Bone formation and graft/binder resorption were compared with a surgical
      grade CS and DBM in paired critical-sized calvarial defects in 25 Wistar rats
      (350-450 g). Six animals each provided paired defects at 7, 14, 21, and 28 days
      postsurgery for nondecalcified processing and microscopic analysis. Defects
      grafted with CS or CS-CMC putty as the DBM binder exhibited similar patterns and
      proportions of bone formation, fibrous tissue/marrow, and residual DBM particles.
      Comparable mean +/- SD proportions of new bone formation (31.7 +/- 9.5 and 33.7
      +/- 12.9), fibrous tissue/marrow (54.2 +/- 8.3 and 53.0 +/- 10.8), residual DBM
      particles (8.3 +/- 6.8 and 10.1 +/- 6.3), and residual binder material (5.5 +/-
      4.6 and 3.7 +/- 3.5) were found at 28 days for defects grafted with CS and CS-CMC
      putty, respectively. Thus, CMC was found to improve the handling characteristics
      of CS and, when used in conjunction with DBM, supported comparable levels bone
      formation and patterns of binder/scaffold resorption as CS and DBM in a calvarial
      defect model.

PMID- 17443668
TI  - Polarized protein membrane for high cell seeding efficiency.
AB  - A new type of scaffold for tissue engineering was developed to give enhanced cell
      seeding in three dimensions. A gradient of either collagen or fibrin protein was
      prepared, supported by a knitted poly(ethylene terephtalate) PET fabric. The
      membranes were, after hydrolysis and acetic acid wash, submerged in a protein
      solution for adsorption followed by immersion into a gelling agent. The immediate
      contact between the protein solution held by the fabric and the gelling agent
      resulted in a dense, fibrous protein network with pore sizes around 0.5 microm at
      the surface, and larger pores of 10-50 microm size throughout the interior of the
      fabric as observed by scanning electron microscopy. By separating the fabric
      double layers holding this network, a gradient porosity membrane was produced. To
      evaluate the fractions of cells trapped in the matrix upon seeding, i.e. the
      seeding efficiency, 500 microl 3T3 fibroblasts cell suspension containing one
      million cells was seeded by filtering through the gradient protein membrane. For
      both the collagen and fibrin membranes, the seeding efficiency was approximately
      93%, which was significantly higher than that of 28% from the corresponding PET
      fabric without protein immobilization. Attempt to seed cells from the dense side
      of the protein networks resulted in no cell penetration into the scaffold.
      Histology on subsequent culture of the cells in the scaffold demonstrated
      viability and proliferation in three dimensions throughout the scaffold. This new
      and simple way of producing scaffolds play an important role when the cells are
      precious or scarce and cell seeding in three dimensions is important.

PMID- 17443669
TI  - Influence of recovering collagen with bioactive glass on osteoblast behavior.
AB  - Bioactive ceramics have interesting properties from the biological standpoint,
      but their effects on cellular events remain partially unknown. In the current
      work, we investigated cellular viability, proliferation, and metabolic activity
      of rat primary osteoblasts in contact with four different samples: type I
      collagen, bioactive glass-coated collagen (GC), and both samples submitted to
      immersion for 5 days in a simulated body fluid. The bioactive glass coating was
      obtained from a sol-gel process. The cell viability, the alkaline phosphate, the
      collagen secretion, and the nitric oxide production by osteoblast were measured
      after 72 h of incubation in the presence of the samples. The GC that was immersed
      for 5 days in a simulated body fluid solution showed an increase in osteoblast
      viability and proliferation when it was compared with control and the other
      samples.

PMID- 17443670
TI  - Determination of haplotypes from single DNA molecules: a method for single
      molecule barcoding.
AB  - Determining the haplotypes in a diploid individual is a major technical challenge
      in genetic studies of human complex traits. Here we report a method of molecular
      haplotyping by directly imaging multiple polymorphic sites on individual DNA
      molecules simultaneously. DNA fragments amplified by long-range PCR were labeled
      with fluorescent dyes at each polymorphic site using a modified gap-filled
      padlock probe ligation approach. The labeled DNA molecules were then stretched
      into linear form on a functionalized glass surface and imaged with multicolor
      total internal reflection fluorescence (TIRF) microscopy. By determining the
      colors and positions of the fluorescent labels with respect to the backbone at
      polymorphic sites, the haplotype can be inferred accurately, in a manner similar
      to reading a barcode, even when the DNA fragments are not fully labeled. The
      feasibility of this technology is demonstrated by the determination of the
      haplotype of a 9.3-kbp DNA fragment containing four SNPs.

PMID- 17443671
TI  - M-CSF-mediated macrophage differentiation but not proliferation is correlated
      with increased and prolonged ERK activation.
AB  - M-CSF is a cytokine essential for both the proliferation and differentiation of
      monocytes/macrophages. In this study, we established a new M-CSF-mediated
      differentiation-inducing system, and examined how the level and duration of the
      activation of ERK preceded M-CSF-mediated differentiation. TF-1-fms human
      leukemia cells rapidly proliferated in response to M-CSF. However, in the
      presence of a phorbol ester, TPA, TF-1-fms cells definitely switched their
      responsiveness to M-CSF from proliferation to differentiation, as evidenced by a
      more drastic morphological change and the appearance of cells with a higher level
      of phagocytic activity. In TF-1-fms cells expressing HIV-1 Nef protein in a
      conditionally active-manner, both M-CSF-mediated proliferation and M-CSF/TPA
      mediated differentiation were inhibited by the activation of Nef. The Nef-active
      cells showed perturbed patterns of ERK activation. Under the proliferation
      inducing conditions (TPA-free), parental or Nef-inactive cells showed modest ERK
      activation following M-CSF stimulation, whereas Nef-active cells showed an
      earlier and transient ERK activation, despite a decrease in their proliferation
      rate. Under the differentiation-inducing conditions, parental or Nef-inactive
      cells showed increased and prolonged ERK activation following M-CSF stimulation,
      whereas Nef-active cells showed transient ERK activation. These results supported
      the idea that the increased and prolonged ERK activation led to M-CSF-mediated
      macrophage differentiation but not to proliferation.

PMID- 17443672
TI  - 14-3-3 sigma isoform interacts with the cytoplasmic domain of the transmembrane
      BP180 in keratinocytes.
AB  - The protein bullous pemphigoid antigen-2 (BPAG2/BP180/collagen type XVII) plays a
      key role in attachment of basal keratinocytes to epidermal basement membrane. The
      binding of BP180 with either integrin alpha6, integrin beta4, or bullous
      pemphigoid antigen-1 (BPAG1/BP230) is critical for this attachment in skin. The
      protein 14-3-3 sigma, also known as stratifin and a marker for epithelial cells,
      is a member of a highly conserved small acidic 14-3-3 protein family naturally
      found in all eukaryotic cells. Here, we have used a 14-3-3sigma GST pull-down
      screening assay and showed that sigma (sigma) isoform of the 14-3-3 protein
      family interacts with the cytoplasmic N-terminal domain of BP180. Analysis of a
      series of truncated or deleted 14-3-3sigma revealed that only intact 14-3-3sigma
      molecule, but not any of its fragments can interact with BP180. This finding
      suggests that conformation and possible dimerization of 14-3-3 sigma is essential
      for this interaction. Further, a BP180 co-immunoprecipitation (IP) and its
      reverse IP assays were conducted and the results confirmed that 14-3-3 sigma
      interacts with cytoplasmic domain, but not ecto-domain of the BP180. In
      conclusion, the finding of this study provides evidence that 14-3-3sigma isoform
      interacts with BP180 which is a major component of hemidesmosome involved in the
      attachment of epidermis to the basement membrane in skin. However, the
      significance of this interaction in hemidesmosome formation and/or attachment
      needs to be explored.

PMID- 17443673
TI  - Thapsigargin induces biphasic fragmentation of mitochondria through calcium
      mediated mitochondrial fission and apoptosis.
AB  - Mitochondrial fission and fusion are the main components mediating the dynamic
      change of mitochondrial morphology observed in living cells. While many protein
      factors directly participating in mitochondrial dynamics have been identified,
      upstream signals that regulate mitochondrial morphology are not well understood.
      In this study, we tested the role of intracellular Ca(2+) in regulating
      mitochondrial morphology. We found that treating cells with the ER Ca(2+)-ATPase
      inhibitor thapsigargin (TG) induced two phases of mitochondrial fragmentation.
      The initial fragmentation of mitochondria occurs rapidly within minutes dependent
      on an increase in intracellular Ca(2+) levels, and Ca(2+) influx into
      mitochondria is necessary for inducing mitochondrial fragmentation. The initial
      mitochondrial fragmentation is a transient event, as tubular mitochondrial
      morphology was restored as the Ca(2+) level decreased. We were able to block the
      TG-induced mitochondrial fragmentation by inhibiting mitochondrial fission
      proteins DLP1/Drp1 or hFis1, suggesting that increased mitochondrial Ca(2+) acts
      upstream to activate the cellular mitochondrial fission machinery. We also found
      that prolonged incubation with TG induced the second phase of mitochondrial
      fragmentation, which was non-reversible and led to cell death as reported
      previously. These results suggest that Ca(2+) is involved in controlling
      mitochondrial morphology via intra-mitochondrial Ca(2+) signaling as well as the
      apoptotic process.

PMID- 17443674
TI  - Dual regulation of upstream binding factor 1 levels by IRS-1 and ERKs in IGF-1
      receptor signaling.
AB  - The Upstream Binding Factor 1 (UBF1) is a nucleolar protein that participates in
      the regulation of RNA polymerase I activity and ribosomal RNA (rRNA) synthesis.
      In 32D myeloid cells expressing the type 1 insulin-like growth factor receptor
      (IGF-IR), the UBF1 protein (but not its mRNA) is down regulated when the cells
      are shifted from Interleukin-3 (IL-3) to IGF-1. Ectopic expression of insulin
      receptor substrate-1 (IRS-1) in these cells inhibits the down-regulation of UBF1.
      We now show that the stability of UBF1 in 32D-derived cells requires also a
      signal from the extracellular regulated kinases (ERKs). When ERKs signaling is
      defective, as in cells over-expressing the insulin receptor (InR) or selected
      mutants of the IGF-1R, UBF1 is down-regulated, even in the presence of IRS-1. The
      down-regulation is corrected by the expression of an activated Ha-ras, which
      stimulates ERKs activity. Mutations at threonines 117 and 201 of UBF1, known to
      be phosphorylated by ERKs, cause its down-regulation. However, when IRS-2,
      instead of IRS-1, is ectopically expressed in 32D InR cells, ERKs phosphorylation
      is increased and UBF is stabilized. Taken together, these results indicate that
      in 32D-derived myeloid cells expressing either the IGF-IR or the InR, UBF1 levels
      are regulated by signaling from both IRS proteins and ERKs.

PMID- 17443675
TI  - Adenovirus E1A proteins direct subcellular redistribution of Nek9, a NimA-related
      kinase.
AB  - A monoclonal antibody raised against adenovirus E1A-associated cellular proteins
      recognized Nek9, a NimA-related protein kinase. Subcellular fractionation and
      immunofluorescence indicated that Nek9 was primarily cytoplasmic with a small
      portion located in the nucleus whereas E1A was primarily nuclear. Although co
      immunoprecipitation experiments indicated that nuclear Nek9 interacted, directly
      or indirectly, with E1A, the major effect of E1A was to diminish the amount of
      Nek9 in the nucleus suggesting that E1A alters the subcellular distribution of
      Nek9 and that the interaction is transient. A Nek9 deletion mutant lacking a
      central RCC1-like domain interacted stably with E1A and accumulated in the
      nucleus in the presence of E1A, possibly representing an intermediate stage of
      the normally transient Nek9/E1A interaction. The interaction of Nek9 with E1A was
      dependent on the N-terminal sequences of E1A. Attempts to stably overexpress
      either Nek9 or the kinase-inactive mutant in various cell lines were
      unsuccessful; however, the presence of E1A allowed stable overexpression of both
      proteins. These results suggest that E1A disrupts a nuclear function of Nek9.

PMID- 17443676
TI  - TNF reduces LIF endocytosis despite increasing NFkappaB-mediated gp130
      expression.
AB  - To examine how the proinflammatory cytokine tumor necrosis factor alpha (TNF)
      modulates the response of cerebral microvessels to other cytokines, we used rat
      cerebral microvessel endothelial RBE4 cells to simulate the in vitro blood-brain
      barrier (BBB). The gp130 receptor, which is shared by the interleukin (IL)-6
      family of cytokines, showed specific upregulation by TNF. TNF treatment (5 ng/ml
      for 30 min to 24 h) increased gp130 at both the levels of transcription and
      protein expression. The stability of gp130 protein was mediated by NFkappaB
      activity, as the inhibitors quinazoline and MG132 not only blocked the increase
      induced by 6 h of TNF treatment, but also reduced its basal level of expression.
      By contrast, the lysosomal inhibitor chloroquine and the extracellular regulated
      kinase inhibitor U0126 showed no effect. Despite the increase of gp130, TNF
      caused a significant reduction in the cell binding and endocytosis of leukemia
      inhibitory factor (LIF), another proinflammatory cytokine that binds to the gp130
      co-receptor and its unique gp190 receptor. This is consistent with our previous
      findings that TNF reduces gp190 expression and Stat3 activation. Thus, TNF
      stimulation results in decreased responsiveness of RBE4 cells to LIF, indicating
      complex regulatory interactions of cytokines at the BBB.

PMID- 17443677
TI  - Spontaneous autocrine release of protons activates ASIC-mediated currents in
      HEK293 cells.
AB  - When examining HEK293 cells by whole-cell patch-clamp electrophysiology we found
      spontaneous currents, present in almost all cells. These currents were carried by
      Na(+) ions, were inhibited by amiloride and by cells exposure to acidic (pH 6.3)
      extracellular solutions. These properties (ion carrier, amiloride-sensitivity,
      and inactivation by constant lowering of extracellular pH) were similar to the
      properties of proton-activated currents measured from the same cells. Spontaneous
      currents required intracellular ATP, were completely inhibited by intracellular
      Ca(2+) buffering with BAPTA and were suppressed by intracellular administration
      of vesicular H(+)ATPase inhibitor bafilomycin. ATP-induced Ca(2+) influx through
      P2X receptors in HEK293 cells stably transfected with P2X(2), P2X(2/3) or P2X(4)
      purinoreceptor subunits transiently potentiated amplitude and frequency of
      spontaneous currents; this effect was antagonized by bafilomycin. We concluded
      that spontaneous currents represent activation of acid-sensitive ion channels
      (ASICs) by autocrine vesicular release of protons from HEK cells.

PMID- 17443678
TI  - Comparison of low-molecular-weight heparin and antithrombin versus antithrombin
      alone for the prevention of symptomatic venous thromboembolism in children with
      acute lymphoblastic leukemia.
AB  - BACKGROUND: Children with acute lymphoblastic leukemia (ALL) have a substantial
      risk for thromboembolism (TE) that is related to L-asparaginase-induced
      antithrombin (AT) deficiency and placement of central venous lines. Recent in
      vitro studies showed that the anticoagulant effects of low-molecular-weight
      heparin were profoundly affected by endogenous AT levels in children undergoing
      ALL therapy. METHODS: A total of 112 consecutively recruited children with newly
      diagnosed ALL treated according to BFM 95/2000 protocols were enrolled in this
      trial. This prospective cohort study was carried out to determine the influence
      of combined low molecular weight heparin-prophylaxis (enoxaparin 1 mg/kg/ per
      day) and AT supplementation versus AT alone (noncontemporaneous control group) on
      the incidence of symptomatic TE during a follow-up of 240 days. RESULTS: To
      maintain AT plasma levels above 50%, nearly 60% of all children needed at least
      one, most children two or three AT supplementations during induction therapy.
      12.7% of the children that did receive only AT-prophylaxis (n = 71) (95% CI = 6.0
      22.7) developed objectively confirmed symptomatic TE, as compared with no TE in
      children after combined prophylaxis (n = 41) (95% CI = 0.0-8.6, P < 0.05).
      Thromboses were located in the sinovenous system in the brain (n = 3), the lower
      deep veins (n = 3), the upper deep veins (n = 2) and in an upper deep vein
      combined with pulmonary embolism (n = 1). CONCLUSION: Prophylaxis with enoxaparin
      was safe and effective in preventing TE. Although our data are encouraging, the
      in vivo efficacy of combined enoxaparin and AT prophylaxis to prevent symptomatic
      venous TE in children with ALL should be evaluated in a prospective randomized
      clinical trial.

PMID- 17443679
TI  - Altered intracellular redox status in Gaucher disease fibroblasts and impairment
      of adaptive response against oxidative stress.
AB  - Gaucher disease (GD) is a lysosomal storage disorder, due to glucosylceramide
      (GlcCer) accumulation in several body tissues, which causes cellular failure by
      yet unidentified mechanisms. Several evidence indicates that GD pathogenesis is
      associated to an impairment in intracellular redox state. In fibroblast primary
      cultures, reactive oxygen species (ROS) levels and protein carbonyl content
      resulted significantly increased in GD patients compared to healthy donors,
      suggesting that GD cells, facing a condition of chronic oxidative stress, have
      evolved an adaptive response to survive. The ROS rise is probably due to NAD(P)H
      oxidase activity, being inhibited by the treatment with diphenylene iodonium
      chloride. Interestingly, GD cells are more sensitive to H(2)O(2) induced cell
      death, suggesting a dysregulation in the adaptive response to oxidative stress in
      which APE1/Ref-1 plays a central role. We found that the cytoplasmic amounts of
      APE1/Ref-1 protein were significantly higher in GD fibroblasts with respect to
      controls, and that GD cells failed to upregulate its expression upon H(2)O(2)
      treatment. Both ROS and APE1/Ref-1 increases are due to GlcCer accumulation,
      being prevented by treatment of GD fibroblasts with Cerezyme and induced in
      healthy fibroblasts treated with conduritol-beta-epoxide. These data, suggesting
      that GD cells display an impairment in the cellular redox state and in the
      adaptive cellular response to oxidative stress, may open new perspectives in the
      comprehension of GD pathogenesis.

PMID- 17443680
TI  - Identification of activity-dependent gene expression profiles reveals specific
      subsets of genes induced by different routes of Ca(2+) entry in cultured rat
      cortical neurons.
AB  - Neuronal activity-dependent gene transcription is a key feature of long-lasting
      synaptic strengthening associated with learning and memory, as well as activity
      dependent neuroprotection. To comprehensively determine the molecular
      alterations, we carried out genome-wide microarray analysis in cultured rat
      cortical neurons treated with specific pharmacological agents, a model with
      alterations in neuronal activity, which were monitored by multi-site
      electrophysiological recordings. Of the approximately 27,000 genes, the
      expression of 248 genes was strongly changed in response to enhanced activity.
      These genes encompass a large number of members of distinct families, including
      synaptic vesicle proteins, ion channels, signal transduction molecules, synaptic
      growth regulators, and others. Two subsets of these genes were further confirmed
      to be specifically induced by Ca(2+) influx through N-methyl-D-aspartate (NMDA)
      receptors and L-type voltage-gated Ca(2+) channels (VGCCs). In addition, those
      genes dynamically regulated by the enhanced activity were also elucidated, as
      well as those candidate genes associated with synaptic plasticity and
      neuroprotection. Our findings therefore would help define the molecular
      mechanisms that occur in response to neuronal activity and identify specific
      clusters of genes that contribute to activity-dependent and Ca(2+)-inducible
      modulation of brain development and function.

PMID- 17443681
TI  - Transcriptional activation by stimulating protein 1 and post-transcriptional
      repression by muscle-specific microRNAs of IKs-encoding genes and potential
      implications in regional heterogeneity of their expressions.
AB  - In cardiac cells, KCNQ1 assembles with KCNE1 and forms a channel complex
      constituting the slow delayed rectifier current I(Ks). Expression of KCNQ1 and
      KCNE1 are regionally heterogeneous and changes with pathological states of the
      heart. The aims of this study were to decipher the molecular mechanisms for
      transcriptional and post-transcriptional regulation expression of KCNQ1 and KCNE1
      genes and to shed light on the molecular mechanisms for their spatial
      heterogeneity of distribution. We cloned the 5'-flanking region and identified
      the transcription start sites of the KCNQ1 gene. We characterized the core
      promoters of KCNQ1 and KCNE1 and revealed the stimulating protein (Sp1) as a
      common transactivator of KCNQ1 and KCNE1 by interacting with the Sp1 cis-acting
      elements in the core promoter regions of these genes. We also characterized the
      3' untranslated regions (3'UTRs) of the genes and experimentally established
      KCNQ1 and KCNE1 as targets for repression by the muscle-specific microRNAs miR
      133 and miR-1, respectively. We demonstrated spatial heterogeneity of KCNQ1 and
      KCNE1 distributions at three axes (interventricular, transmural and apical-basal)
      and disparity between mRNA and protein expressions of these genes. We also found
      characteristic regional differences of expressions of Sp1 and miR-1/miR-133 in
      the heart. Our study unraveled a novel aspect of the cellular function of miRNAs
      and suggests that the I(Ks)-encoding genes KCNQ1 and KCNE1 expressions are
      dynamically balanced by transcription factor regulation and miRNA repression. The
      heterogeneities of Sp1 and miR-1/miR-133 offer an explanation for the well
      recognized regional differences and disparity between mRNA and protein
      expressions of KCNQ1 and KCNE1.

PMID- 17443682
TI  - Present concepts and future outlook: function of peroxisome proliferator
      activated receptors (PPARs) for pathogenesis, progression, and therapy of cancer.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      receptor superfamily of transcriptional regulators that regulate lipid, glucose,
      and amino acid metabolism. In recent studies it also has been shown that these
      receptors are implicated in tumor progression, cellular differentiation, and
      apoptosis and modulation of their function is therefore considered as a potential
      target for cancer prevention and treatment. PPAR ligands and other agents
      influencing PPAR signalling pathways have been shown to reveal chemopreventive
      potential by mediating tumor suppressive activities in a variety of human cancers
      and could represent a potential novel strategy to inhibit tumor carcinogenesis
      and progression. This review summarizes the currently available data on the roles
      of PPARs in relation to the processes of cell differentiation and carcinogenesis
      as well as their role as promising future therapeutic targets.

PMID- 17443683
TI  - Parathyroid hormone-related protein (PTHrP) inhibits mitochondrial-dependent
      apoptosis through CK2.
AB  - Over the past decade, parathyroid hormone-related protein (PTHrP) has been
      identified as a key survival factor for cells subjected to apoptotic stimuli. Its
      anti-apoptotic activity has been attributed to nuclear accumulation of the intact
      protein, or a synthetic peptide corresponding to its nuclear targeting sequence
      (NTS), which promotes rapid exit of nutrient deprived cells from the cell cycle.
      Intracellular PTHrP also inhibited apoptosis by blocking tumor necrosis factor
      alpha (TNFalpha)-induced apoptosis by blocking signaling from the "death
      receptor" and preventing damage to the mitochondrial membrane. In both cases, the
      anti-apoptotic activity was significantly reduced in the presence of a nuclear
      deficient form of PTHrP with a (88)K/E K/E.K/I(91) mutation in the NTS. The
      current work was undertaken to determine the mechanism by which nuclear PTHrP
      blocked mitochondrial-mediated apoptosis. Using sub-cellular fractionation and
      functional assays we showed that pre-treatment of HEK293 cells with exogenous NTS
      peptide before inducing apoptosis with TNFalpha was as effective as expression of
      the full-length protein in inhibiting apoptosis. Inhibition of apoptosis was
      associated with increased expression of protein kinase casein kinase 2 (CK2) and
      in sustained CK2 accumulation and activity in the nuclear fraction. In primary
      chondrogenic cells harvested from the limb buds of PTHrP(+/-) and PTHrP(-/-)
      embryonic mice, there was a dose-dependent decrease in CK2 expression and
      activity that correlated with increased susceptibility to apoptosis. Taken
      together the results indicate that nuclear accumulation of PTHrP effectively
      inhibits mitochondrial-mediated apoptosis through regulation of the expression,
      activity, and sub-cellular trafficking of CK2.

PMID- 17443684
TI  - Proteasomes and RARS modulate AIMP1/EMAP II secretion in human cancer cell lines.
AB  - The aminoacyl t-RNA synthetase interacting multifunctional protein (AIMP1) is the
      precursor of the multifunctional inflammatory cytokine endothelial monocyte
      activating polypeptide II (EMAP II). We previously demonstrated that AIMP1
      secretion by pituitary adenomas is inversely correlated with tumor diameter and
      with RARS expression, suggesting that a high amount of RARS associated with AIMP1
      might prevent the secretion of the latter cytokine. In this study, we
      investigated the role of RARS in modulating the secretion of AIMP1 in HeLa and
      MCF7 cell lines and investigated the possible role of the multicatalytic protease
      in the cleavage of AIMP1 to generate EMAP II. Our data show that RARS over
      expression impairs AIMP1 secretion by both HeLa and MCF7 cells. Moreover,
      proteasome inhibition impairs AIMP1 cleavage to produce EMAP II. These data
      indicate that RARS over-expression associates with a reduced AIMP1 secretion and
      that the multicatalytic protease is involved in the generation of the mature
      cytokine, EMAP II.

PMID- 17443685
TI  - Alveolar progenitor cells develop in mouse mammary glands independent of
      pregnancy and lactation.
AB  - We have previously described pluripotent, parity-induced mammary epithelial cells
      (PI-MEC) marked by Rosa26-lacZ expression in the mammary glands of parous
      females. PI-MEC act as lobule-limited epithelial stem/progenitor cells. To
      determine whether parity is necessary to generate PI-MEC, we incubated mammary
      explant cultures from virgin mice in vitro with insulin alone (I), hydrocortisone
      alone (H), prolactin alone (Prl), or a combination of these lactogenic hormones
      (IHPrl). Insulin alone activated the WAP-Cre gene. Hydrocortisone and prolactin
      alone did not. Any combination of hormones that included insulin was effective.
      Only I, H and Prl together were able to induce secretory differentiation and milk
      protein synthesis. In addition, EGF, IGF-2 and IGF-1 added individually produced
      activated (lacZ(+)) PI-MEC in explant cultures. Neither estrogen nor progesterone
      induced WAP-Cre expression in the explants. None of these positive initiators of
      WAP-Cre expression in PI-MEC were effective in mammospheres or two-dimensional
      cultures of mammary epithelium, indicating the indispensability of epithelial
      stromal interaction in PI-MEC activation. Like PI-MEC, lacZ(+) cells from virgin
      explants proliferated and contributed progeny to mammospheres in vitro and to
      epithelial outgrowths in vivo after transplantation. LacZ(+) cells induced in
      virgin mouse mammary explants were multipotent (like PI-MEC) in impregnated hosts
      producing lacZ(+) mammary alveolar structures comprised of both myoepithelial and
      luminal progeny. These data demonstrate PI-MEC, a mammary epithelial sub
      population of lobule-limited progenitor cells, are present in nulliparous female
      mice before parity and, like the PI-MEC observed following parity, are capable of
      proliferation, self-renewal and the capacity to produce progeny of diverse
      epithelial cell fates.

PMID- 17443686
TI  - Redox control of G(1)/S cell cycle regulators during nitric oxide-mediated cell
      cycle arrest.
AB  - Redox regulation of cell cycle progression during nitric oxide (NO) mediated
      cytostasis is not well-understood. In this study, we investigated the role of the
      intracellular antioxidant glutathione (GSH) in regulating specific signaling
      events that are associated with NO-mediated cell cycle arrest. Manipulation of
      intracellular GSH content through pharmacological inhibition of glutamate
      cysteine ligase (GCL) indicated that GSH depletion potentiated nitrosative
      stress, DNA damage, phosphorylation of the tumor suppressor p53 (Ser-18) and
      upregulation of p21(cip1/waf1) upon NO stimulation. However, we found that
      neither overexpression of a dominant negative p53 nor pharmacological inhibition
      of p53 with cyclic pifithrin-alpha (cPFT-alpha) was sufficient to reverse NO
      mediated cell cycle arrest or hypophosphorylation of retinoblastoma protein (Rb).
      We found that the decrease in cyclin D1 levels induced by NO was GSH-sensitive
      implying that the redox regulation of NO-mediated cytostasis was a multifaceted
      process and that both p53/p21(cip1/waf1) and p53 independent cyclin D1 pathways
      were involved. Together, our results demonstrate that GSH serves as an important
      component of cellular protective mechanisms against NO-derived nitrosative stress
      to regulate DNA damage checkpoint.

PMID- 17443687
TI  - Zinc regulates the ability of Cdc25C to activate MPF/cdk1.
AB  - Zn(2+) is an essential micronutrient for the growth and development of
      multicellular organisms, as Zn(2+) deficiencies lead to growth retardation and
      congenital malformations (Vallee, BL, Falchuk, KH. 1993. Physiol Rev., 73:79
      118). At the cellular level Zn(2+) depravation results in proliferation defects
      in many cell types (Vallee, BL, Falchuk, KH. 1993. Physiol Rev., 73:79-118),
      however the molecular pathways involved remain poorly defined. Here we show that
      the transition metal chelator TPEN (N,N,N',N'-tetrakis(2-pyridylmethyl) ethylene
      diamine) blocks the G2/M transition of the meiotic cell cycle by inhibiting
      Cdc25C-cdk1 activation. ICP-MS analyses reveal that Cdc25C is a Zn(2+)-binding
      metalloprotein, and that TPEN effectively strips Zn(2+) away from the enzyme.
      Interestingly, although apo-Cdc25C (Zn(2+)-deficient) remains fully catalytically
      active, it is compromised in its ability to dephosphorylate and activate
      MPF/cdk1. Thus, Zn(2+) is an important regulator of Cdc25C function in vivo.
      Because of the conserved essential role of the Cdc25C-cdk1 module in the
      eukaryotic cell cycle, these studies provide fundamental insights into cell cycle
      regulation.

PMID- 17443688
TI  - Glutamate is a determinant of cellular proliferation through modulation of
      nuclear factor E2 p45-related factor-2 expression in osteoblastic MC3T3-E1 cells.
AB  - Activation of particular glutamate (Glu) receptors is shown to promote cellular
      differentiation toward maturation during osteoblastogenesis. In the present
      study, we have evaluated the possible modulation by Glu of cellular proliferation
      in osteoblastic cells endowed to proliferate for self-renewal and to
      differentiate toward matured osteoblasts. Exposure to Glu significantly
      suppressed the proliferation activity at a concentration over 500 microM without
      inducing cell death in osteoblastic MC3T3-E1 cells before differentiation. The
      suppression by Glu occurred in a manner sensitive to the prevention by either
      cystine or reduced glutathione. Expression of mRNA was for the first time shown
      with the cystine/Glu antiporter composed of xCT and 4F2hc subunits in these
      undifferentiated osteoblastic cells. A significant decrease was seen in
      intracellular total glutathione levels in undifferentiated MC3T3-E1 cells
      cultured with Glu, indeed, whereas the cellular proliferation activity was
      drastically decreased by the addition of the glutathione depleter cyclohexene-1
      one and the glutathione biosynthesis inhibitor L-buthionine-[S,R]-sulfoximine,
      respectively. Exposure to Glu led to a significant increase in mRNA expression of
      nuclear factor E2 p45-related factor 2 (Nrf2) together with the generation of
      reactive oxygen species, while a significant decrease was seen in the
      proliferation activity in MC3T3-E1 cells with stable overexpression of Nrf2.
      These results suggest that Glu could suppress the cellular proliferation toward
      self-renewal through a mechanism associated with the upregulation of Nrf2
      expression in association with the depletion of intracellular glutathione after
      promoting the retrograde operation of the cystine/Glu antiporter in
      undifferentiated MC3T3-E1 cells.

PMID- 17443689
TI  - Epigenetic inactivation of the metastasis suppressor RECK enhances invasion of
      human colon cancer cells.
AB  - Down-regulation of RECK, an important metastasis suppressor gene, has been found
      in human colon cancer. However, the molecular mechanism for this down- regulation
      and its biological significance are still unclear. In the present study, we
      investigated whether down-regulation of RECK is caused by epigenetic inactivation
      via promoter methylation and tested the effect of DNA methyltransferase (DNMT)
      inhibitor on RECK expression and cell invasion. The mRNA and protein levels of
      RECK in colon tumor tissues and their normal counterparts were compared. We found
      that down-regulation of RECK was found in 48% of the twenty five tumors analyzed.
      MSP analysis demonstrated that methylation of RECK promoter was detected in 44%
      (11/25) of the tumor tissues and a strong correlation between down-regulation and
      promoter methylation was found (P = 0.028). Promoter methylation was also found
      in SW480 and SW620 human colon cancer cell lines. DNA methyltransferase (DNMT)
      inhibitor 5'-azacytidine reversed promoter methylation, restored RECK expression
      and suppressed invasion by these two cell lines. Restoration of RECK is critical
      for 5'-azacytidine-mediated suppression of cell invasion because inhibition of
      RECK by a specific antibody significantly attenuated the anti-invasive ability of
      5'-azacytidine. Taken together, our results suggest that down-regulation of the
      metastasis suppressor RECK in colon cancer is associated with promoter
      methylation and that a DNMT inhibitor may restore RECK expression to inhibit cell
      invasion.

PMID- 17443690
TI  - Oxidative stress and increased eNOS and NADPH oxidase expression in mouse
      microvessel endothelial cells.
AB  - Elevated oxidative stress plays a key role in diabetes-associated vascular
      disease. In this study, we tested the hypothesis that high glucose-induced
      oxidative stress was associated with changes in the expression of NADPH oxidase,
      superoxide dismutase (SOD) and endothelial nitric oxide synthase (eNOS).
      Oxidative stress was assessed in cell cultures of mouse microvessel endothelial
      cells (MMECs) by fluorescence labelling with dihydroethidium, lucigenin-enhanced
      chemiluminescence and determining NADPH oxidase subunit and eNOS expression with
      real-time polymerase chain reaction protocol and Western blotting. Oxidative
      stress and expression of the NADPH oxidase subunit, p22phox, were both increased,
      SOD1 and 3 expression lowered and eNOS significantly elevated in MMECs treated
      with 40 mM glucose for 72 h compared to low glucose medium. Oxidative stress,
      p22phox mRNA, eNOS mRNA, and protein were lowered by concurrent incubation with
      sepiapterin. When eNOS protein expression in endothelial cells was significantly
      decreased by eNOS siRNA treatment, superoxide generation was significantly higher
      in the MMECs grown in low glucose, but reduced in those grown in high glucose for
      72 h. Thus, exposure of MMECs to high glucose results in increased oxidative
      stress that is associated with increased eNOS and NADPH oxidase subunit
      expression, notably p22phox, and decreased expression of SOD1 and 3.

PMID- 17443691
TI  - Long-term cognitive profile and incidence of dementia after STN-DBS in
      Parkinson's disease.
AB  - An effect of subthalamic nucleus deep brain stimulation (STN-DBS) on cognition
      has been suspected but long-term observations are lacking. The aim of this study
      was to evaluate the long-term cognitive profile and the incidence of dementia in
      a cohort of Parkinson's disease (PD) patients treated by STN-DBS. 57 consecutive
      patients were prospectively assessed by the mean of a neuropsychological battery
      over 3 years after surgery. Dementia (DSM-IV) and UPDRS I to IV were recorded.
      24.5% of patients converted to dementia over 3 years (incidence of 89 of 1,000
      per year). This group of patients cognitively continuously worsened over 3 years
      up to fulfilling dementia criteria (PDD). The rest of the cohort remained
      cognitively stable (PD) over the whole follow-up. Preoperative differences
      between PDD and PD included older age (69.2 +/- 5.8 years; 62.6 +/- 8 years),
      presence of hallucinations and poorer executive score (10.1 +/- 5.9; 5.5 +/-
      4.4). The incidence of dementia over 3 years after STN-DBS is similar to the one
      reported in medically treated patients. The PDD presented preoperative risk
      factors of developing dementia similar to those described in medically treated
      patients. These observations suggest dementia being secondary to the natural
      evolution of PD rather than a direct effect of STN-DBS.

PMID- 17443692
TI  - Levodopa response in long-term bilateral subthalamic stimulation for Parkinson's
      disease.
AB  - Subthalamic nucleus deep brain stimulation (STN-DBS) is effective in advanced
      Parkinson's disease (PD), but its effects on the levodopa response are unclear.
      We studied the levodopa response after long-term STN-DBS, STN-DBS efficacy and
      predictive value of preoperative levodopa response to long-term DBS benefit in 33
      PD patients with bilateral STN-DBS. Patients were assessed using the Unified
      Parkinson's Disease Rating Scale preoperatively (with and without medications)
      and postoperatively (without medications or stimulation, with only medications or
      stimulation, and with both medications and stimulation). Levodopa response
      significantly decreased postoperatively by 31.1% at 3 years and 32.3% at 5 years,
      possibly related to the reduction in medication requirement, direct STN
      stimulation effect or PD progression. STN-DBS alone significantly improved motor
      scores (37.2% at 3 years and 35.1% at 5 years) and activities of daily living
      scores (27.1% at 3 years and 19.2% at 5 years). Anti-PD drugs were significantly
      reduced by 47.9% at 3 years and 39.8% at 5 years. However, the magnitude of the
      preoperative response to levodopa did not predict DBS benefit at 3 and 5 years.

PMID- 17443694
TI  - Tibolone: example of qualitative and quantitative assessments of the mammary
      gland.

PMID- 17443695
TI  - Evaluation of aflatoxin B1 embryotoxicity using the frog embryo teratogenesis
      assay-Xenopus and bio-activation with microsome activation systems.
AB  - BACKGROUND: Aflatoxins are a group of mycotoxins produced by Aspergillus, A.
      flavus, and A. parasiticus. Aflatoxin B1 (AFB1) should be a strong teratogen in
      hamsters, but its effect in rats is equivocal and extremely limited in mice.
      Therefore, the AFB1 embryotoxic potential in mammals remains unclear. METHODS:
      Little is known about the AFB1 effects on amphibians, therefore its embryotoxic
      potential was evaluated using the frog embryo teratogenesis assay-Xenopus
      (FETAX). X. laevis blastulae were exposed to: 1) positive controls for bio
      activation (4 g/L cyclophosphamide monohydrate, Cy, and 4 g/L Cy+30 mg/L MAS-rat;
      4 g/L Cy+30 mg/L MAS-human); 2) positive controls for MAS (30 mg/L MAS-rat and 30
      mg/L MAS-human); 3) exposed groups to AFB1 (1 mg/L AFB1); and 4) AFB1 bio
      activation (1 mg/L AFB1+30 mg/L MAS-rat and 1 mg/L AFB1 +30 mg/L MAS-human).
      RESULTS: In MAS-rat and human, Cy did not induce a statistically significant
      increase of mortality and malformed larvae percentage, but when bio-activated Cy
      increased the percentage of mortality. Instead, MAS-rat and human alone did not
      show any increase of mortality and malformed larvae percentages. When bio
      activated by MAS-rat and human, AFB1 increased significantly both the mortality
      and malformed larvae percentages. The malformed larvae were mainly
      plurimalformed, i.e., affected by generalized edema, abnormal gut coiling, and
      microphthalmia. CONCLUSIONS: This research shows that AFB1 alone is not
      embryotoxic but, when bio-activated with MAS-rat or MAS-human the percentage of
      mortality and malformed larvae increased significantly. These results also show
      that AFB1 must be bio-activated to exert its embryotoxic effects.

PMID- 17443696
TI  - Contribution of Jules Froment to the study of parkinsonian rigidity.
AB  - Rigidity is commonly defined as a resistance to passive movement. In Parkinson's
      disease (PD), two types of rigidity are classically recognized which may coexist,
      "leadpipe " and "cogwheel". Charcot was the first to investigate parkinsonian
      rigidity during the second half of the nineteenth century, whereas Negro and
      Moyer described cogwheel rigidity at the beginning of the twentieth century.
      Jules Froment, a French neurologist from Lyon, contributed to the study of
      parkinsonian rigidity during the 1920s. He investigated rigidity of the wrist at
      rest in a sitting position as well as in stable and unstable standing postures,
      both clinically and with physiological recordings using a myograph. With Gardere,
      Froment described enhanced resistance to passive movements of a limb about a
      joint that can be detected specifically when there is a voluntary action of
      another contralateral body part. This has been designated in the literature as
      the "Froment's maneuver " and the activation or facilitation test. In addition,
      Froment showed that parkinsonian rigidity diminishes, vanishes, or enhances
      depending on the static posture of the body. He proposed that in PD "maintenance
      stabilization " of the body is impaired and that "reactive stabilization "
      becomes the operative mode of muscular tone control. He considered
      "rigidification " as compensatory against the forces of gravity. Froment also
      demonstrated that parkinsonian rigidity increases during the Romberg test, gaze
      deviation, and oriented attention. In their number, breadth, and originality,
      Froment's contributions to the study of parkinsonian rigidity remain currently
      relevant to clinical and neurophysiological issues of PD.

PMID- 17443699
TI  - Health related quality of life in patients with dystonia and their caregivers in
      New Zealand and Australia.
AB  - Health Related Quality of Life (HRQL) was assessed by the SF-36 in a group of
      patients with dystonia in New Zealand and Australia. The caregivers of these
      people were also asked to participate. Low scores from the SF-36 indicate a
      disability or limitation in HRQL. Compared with the national norms of the
      respective countries, the participants with dystonia for both countries were
      significantly lower in the eight dimensions of the SF-36, suggesting that
      patients with dystonia have lower HRQL compared with their respective national
      norms without dystonia. In contrast to the patients with dystonia, caregivers did
      not show lower HRQL scores than their national norms, suggesting that while
      dystonia affects the HRQL of those with the disorder, their caregivers may be
      less affected. Descriptive and demographic information were also gathered and are
      discussed. An important factor that may affect the HRQL of patients with dystonia
      is the length of time required to be diagnosed in this sample and the number of
      medical practitioners the patients consulted prior to a confirmed diagnosis.

PMID- 17443700
TI  - Morphometric changes of sensorimotor structures in focal dystonia.
AB  - Idiopathic cervical dystonia (CD) and benign essential blepharospasm (BEB) are
      the most common forms of focal dystonia. Previous autopsy and imaging studies
      suggested that these disorders are not accompanied by structural brain
      abnormalities. However, recent brain voxel-based morphometry (VBM) studies of
      these conditions suggest that there actually may be changes in gray matter. The
      objective of this stdy was to detect possible gray matter abnormalities in
      patients with CD and BEB using VBM and to compare the results between the two
      conditions and with age- and gender-matched controls. High-resolution MRI was
      employed to evaluate healthy controls and individuals with BEB and CD. Eleven
      BEB, 9 CD, and 14 healthy control subjects were imaged. VBM revealed alterations
      of gray matter structures involved in sensorimotor processing in the individuals
      with focal dystonia. In CD subjects there was increased gray matter in the
      thalamus, caudate head bilaterally, superior temporal lobe, and left cerebellum,
      while gray matter was decreased in the putamen bilaterally. BEB subjects had
      increased gray matter in the caudate head and cerebellum bilaterally as well as
      decrease in the putamen and thalamus bilaterally. These findings strongly
      underline the recent notion that idiopathic focal dystonias might have a
      detectable structural correlate. They also demonstrate structural similarities of
      the investigated focal dystonias, possibly reflecting a shared common
      pathophysiological origin.

PMID- 17443701
TI  - Cortical actin filament organization in developing and functioning stomatal
      complexes of Zea mays and Triticum turgidum.
AB  - Cortical actin filament (AF) organization was studied in detail in developing
      stomatal complexes of the grasses Zea mays and Triticum turgidum. AF arrays
      during the whole stomatal complex development are dynamic, partly following the
      pattern of cortical microtubule (MT) organization. They also exhibit particular
      patterns of organization, spatially and temporarily restricted. Among AF arrays,
      the radial ones that underlie young guard cell (GC) periclinal walls, those that
      line the bulbous GC ends and the AF ring at the junction between subsidiary cells
      (SCs) and GCs are described here for the first time. Although many similarities
      in cortical AF organization exist among the stomatal cells of both plants
      studied, considerable differences have also been observed between them. Our data
      reveal that the expanding areas of stomatal cell walls are lined by distinct
      cortical AF aggregations that probably protect the plasmalemma against mechanical
      stresses. Experimental AF disruption does not seem to affect detectably stomatal
      cell morphogenesis. Moreover, the structural and experimental data of this study
      revealed that, in contrast to the elliptical stomata, in the dumbbell-shaped ones
      the AFs and MTs seem not to be involved in the mechanism of opening and closing
      of the stomatal pore.

PMID- 17443702
TI  - Striatal delivery of CERE-120, an AAV2 vector encoding human neurturin, enhances
      activity of the dopaminergic nigrostriatal system in aged monkeys.
AB  - Neurturin (NTN) is a potent survival factor for midbrain dopaminergic neurons.
      CERE-120, an adeno-associated virus type 2 (AAV2) vector encoding human NTN (AAV2
      NTN), is currently being developed as a potential therapy for Parkinson's
      disease. This study examined the bioactivity and safety/tolerability of AAV2-NTN
      in the aged monkey model of nigrostriatal dopamine insufficiency. Aged rhesus
      monkeys received unilateral injections of AAV2-NTN into the caudate and putamen,
      with each animal therefore serving as its own control. Robust expression of NTN
      within the nigrostriatal system was observed 8 months postadministration. (18)F
      fluorodopa imaging using positron emission tomography revealed statistically
      significant increases in (18)F-fluorodopa uptake in the injected striatum
      compared with the uninjected side at 4 and 8 months. In addition, at 8 months
      postadministration, a significant enhancement in tyrosine hydroxylase
      immunoreactive fibers and an increase in the number of tyrosine hydroxylase
      immunoreactive cells was observed in the AAV2-NTN injected striatum compared with
      the uninjected side. Robust activation of phosphorylated extracellular signal
      regulated kinase immunoreactivity in the substantia nigra was also observed.
      Histopathological analyses revealed no adverse effects of AAV2-NTN in the brain.
      Collectively, these results are consistent with the neurotrophic effects of NTN
      on the dopaminergic nigrostriatal system and extend the growing body of evidence
      supporting the concept that AAV2-NTN may have therapeutic benefit for Parkinson's
      disease.

PMID- 17443703
TI  - Low plasma uric acid level in Parkinson's disease.
AB  - Earlier studies suggest that low plasma uric acid level is a risk factor for
      Parkinson's disease (PD), and that uric acid associates with iron-binding
      proteins. We therefore decided to examine plasma uric acid levels and markers of
      peripheral iron metabolism in PD patients and healthy controls. For the study, 40
      patients with PD and 29 controls underwent clinical screening, laboratory
      testing, and body mass index (BMI) measurement. The average consumption of
      different foodstuffs and dairy products was estimated. Plasma uric acid level was
      significantly lower in the patients than in the controls. There were no
      significant differences in the levels of plasma iron parameters, but plasma uric
      acid correlated strongly with serum ferritin both in the patient and the control
      group. The BMI was slightly lower in the patients compared with the controls
      despite equal daily calorie consumption. Plasma uric acid level is low in
      patients with PD, which may have implications for both the disease pathogenesis
      and treatment recommendations.

PMID- 17443704
TI  - A new association test using haplotype similarity.
AB  - Association tests based on multi-marker haplotypes may be more powerful than
      those based on single markers. The existing association tests based on multi
      marker haplotypes include Pearson's chi2 test which tests for the difference of
      haplotype distributions in cases and controls, and haplotype-similarity based
      methods which compare the average similarity among cases with that of the
      controls. In this article, we propose new association tests based on haplotype
      similarities. These new tests compare the average similarities within cases and
      controls with the average similarity between cases and controls. These methods
      can be applied to either phase-known or phase-unknown data. We compare the
      performance of the proposed methods with Pearson's chi2 test and the existing
      similarity-based tests by simulation studies under a variety of scenarios and by
      analyzing a real data set. The simulation results show that, in most cases, the
      new proposed methods are more powerful than both Pearson's chi2 test and the
      existing similarity-based tests. In one extreme case where the disease mutant
      induced at a very rare haplotype (<or=3%), Pearson's chi2 is slightly more
      powerful than the new proposed methods, and in this case, the existing similarity
      based tests have almost no power. In another extreme case where the disease
      mutant was introduced at the most common haplotype, the existing similarity-based
      methods are slightly more powerful than the new proposed methods, and in this
      case Pearson's chi2 test is least powerful. The results of real data analysis are
      consistent with that of our simulation studies.

PMID- 17443705
TI  - Diagnosis of Parkinsonism in older patients receiving sodium valproate.

PMID- 17443706
TI  - "Prodromic" tremor: prevalence and clinical correlates.

PMID- 17443707
TI  - Huntington's disease presenting as postsurgical psychosis.

PMID- 17443708
TI  - A range of simple summary genome-wide statistics for detecting genetic linkage
      using high density marker data.
AB  - A simple approach to design and analysis of genome-wide linkage scans is
      described, based on an approximation to the joint distribution of likelihood
      ratio statistics at a large number of single nucleotide polymorphism (SNP) loci.
      The approximation is readily calculated and makes it feasible to study the test
      properties of a range of summary statistics for the entire sequence of point-wise
      test values. Both the null distribution in the absence of genetic effects and the
      alternative distribution under various models of single or multi-gene inheritance
      can readily be simulated. This allows the power of a variety of statistics to be
      evaluated. The most powerful statistics proved to be the "quantile statistics"
      defined as quantiles of the set of pointwise test statistics. As a proof of
      principle study, the method was applied to a small dataset of 40 individuals from
      8 families known to be segregating mutations in one or other of the DNA mismatch
      repair genes, MLH1 and MSH2. These included seven affected sib pairs and 11
      discordant sib pairs, who were genotyped at 57,429 autosomal SNPs using the
      Affymetrix GeneChip Human Mapping 50 k Xba 240 Array. While the sample size was
      not sufficient to detect the linkage, there was a clear signal at the MLH1
      location indicating that relatively small sample sizes would have been adequate
      to detect linkage to this gene.

PMID- 17443709
TI  - Enhancement of rigidity in Parkinson's disease with activation.
AB  - Rigidity, a cardinal symptom of Parkinson's disease (PD), increases with movement
      of a contralateral limb. It is unclear whether this effect is specific for
      movement of a contralateral limb. The goal of this study was to test the
      hypothesis that ipsilateral or contralateral movement would enhance rigidity but
      that bilateral limb movements would maximally increase rigidity in people with
      PD. We assessed rigidity in 12 people with PD off meds, 12 matched controls, and
      10 young controls, using a Rigidity Analyzer (Neurokinetics, Alberta, Canada).
      The elbow was passively moved repetitively into flexion and extension by the
      examiner, while the subjects engaged in different toe tapping conditions: no
      tapping, ipsilateral tapping, contralateral tapping, and bilateral tapping. Three
      50-second trials were done for each condition and the order of the trials was
      randomized. A 2-way repeated measures ANOVA and Holm-Sidak post hoc tests were
      used to determine differences across conditions and groups. There was a
      significant effect of group, tapping conditions and an interaction of the two.
      Post hoc tests revealed that for the PD group, all tapping conditions were
      significantly different from the no tapping condition but not different from each
      other. There were no differences across conditions for the controls. We conclude
      that movement of either the contralateral or ipsilateral lower extremity can
      increase arm rigidity in people with PD but the effects from left and right are
      apparently not additive. Further, activation did not enhance muscle tone in
      controls suggesting that this procedure may help distinguish people with PD from
      controls.

PMID- 17443710
TI  - Improving estimates of genetic maps: a meta-analysis-based approach.
AB  - Inaccurate genetic (or linkage) maps can reduce the power to detect linkage,
      increase type I error, and distort haplotype and relationship inference. To
      improve the accuracy of existing maps, I propose a meta-analysis-based method
      that combines independent map estimates into a single estimate of the linkage
      map. The method uses the variance of each independent map estimate to combine
      them efficiently, whether the map estimates use the same set of markers or not.
      As compared with a joint analysis of the pooled genotype data, the proposed
      method is attractive for three reasons: (1) it has comparable efficiency to the
      maximum likelihood map estimate when the pooled data are homogeneous; (2)
      relative to existing map estimation methods, it can have increased efficiency
      when the pooled data are heterogeneous; and (3) it avoids the practical
      difficulties of pooling human subjects data. On the basis of simulated data
      modeled after two real data sets, the proposed method can reduce the sampling
      variation of linkage maps commonly used in whole-genome linkage scans.
      Furthermore, when the independent map estimates are also maximum likelihood
      estimates, the proposed method performs as well as or better than when they are
      estimated by the program CRIMAP. Since variance estimates of maps may not always
      be available, I demonstrate the feasibility of three different variance
      estimators. Overall, the method should prove useful to investigators who need map
      positions for markers not contained in publicly available maps, and to those who
      wish to minimize the negative effects of inaccurate maps.

PMID- 17443711
TI  - Protein recognition motifs: design of peptidomimetics of helix surfaces.
AB  - Helices represent one of the most common recognition motifs in proteins. The
      design of nonpeptidic scaffolds, such as the 3,2',2''-tris-substituted terphenyl,
      that can imitate the side-chain orientation along one face of an alpha-helix
      potentially provides an effective means to modulate helix-recognition functions.
      Here, based on theoretical arguments, we described novel alpha-helix mimetics
      which are more effective than the terphenyl at constraining the aryl-aryl torsion
      angles to those associated with structures suitable for mimicking the alpha
      helical twist for side-chain orientation and for superimposing the side chains of
      residues i, i + 3 or i + 4, i + 7 when compared with the alpha-beta side-chain
      vectors of the regular alpha-helix with an improved root mean square deviation
      (RMSD) of approximately 0.5 A. In addition, this study suggests that rotamer
      distributions around the C(alpha)--C(beta) bonds of these helix mimetics are
      similar to those of alpha-helices, except that these rotamer distributions show
      an approximately 60 degrees shift compared to those of alpha-helices when the
      mimetic axis is superimposed upon the helix axis. This change in rotamer
      orientation complicates mimicry of the helix surface.

PMID- 17443712
TI  - Peptide design and structural characterization of a GPCR loop mimetic.
AB  - G protein-coupled receptors (GPCRs) control fundamental aspects of human
      physiology and behaviors. Knowledge of their structures, especially for the loop
      regions, is limited and has principally been obtained from homology models,
      mutagenesis data, low resolution structural studies, and high resolution studies
      of peptide models of receptor segments. We developed an alternate methodology for
      structurally characterizing GPCR loops, using the human S1P(4) first
      extracellular loop (E1) as a model system. This methodology uses computational
      peptide designs based on transmembrane domain (TM) model structures in
      combination with CD and NMR spectroscopy. The characterized peptides contain
      segments that mimic the self-assembling extracellular ends of TM 2 and TM 3
      separated by E1, including residues R3.28(121) and E3.29(122) that are required
      for sphingosine 1-phosphate (S1P) binding and receptor activation in the S1P(4)
      receptor. The S1P(4) loop mimetic peptide interacted specifically with an S1P
      headgroup analog, O-phosphoethanolamine (PEA), as evidenced by PEA-induced
      perturbation of disulfide cross-linked coiled-coil first extracellular loop
      mimetic (CCE1a) (1)H and (15)N backbone amide chemical shifts. CCE1a was capable
      of weakly binding PEA near biologically relevant residues R29 and E30, which
      correspond to R3.28 and E3.29 in the full-length S1P(4) receptor, confirming that
      it has adopted a biologically relevant conformation. We propose that the
      combination of coiled-coil TM replacement and conformational stabilization with
      an interhelical disulfide bond is a general design strategy that promotes native
      like structure for loops derived from GPCRs.

PMID- 17443713
TI  - Assessing the mammary gland of nonhuman primates: effects of endogenous hormones
      and exogenous hormonal agents and growth factors.
AB  - This review provides a summary of the normal biology, development, and morphology
      of the breast in nonhuman primates (macaques), and of the major published work
      addressing hormonally-induced changes in the breast of these animals. The mammary
      glands of macaques are anatomically, developmentally, and physiologically similar
      to the human breast, with similar expression of sex steroid receptors (estrogen
      receptors alpha and beta, progesterone receptor A and B, androgen receptors),
      estrogen dependent markers, and steroid metabolizing enzymes. Genetic similarity
      between human beings and macaques is high, varying from 95-99% depending on the
      sequence evaluated. Macaques develop hyperplastic and cancerous lesions of the
      breast spontaneously, which are similar in type and prevalence to those of human
      beings. They have a reproductive physiology typical of anthropoid primates,
      including a distinct menarche and menopause, and a 28-day menstrual cycle. These
      similarities give unique value to the macaque model for evaluation of the
      effectiveness and safety of hormonal agents. Such agents considered in this
      review include estrogens and progestogens, combined therapies such as oral
      contraceptives and post-menopausal hormone therapies, androgens, selective
      estrogen receptor modulators, phytoestrogens, prolactin, somatotropin, epidermal
      growth factor, and other novel agents with hormonal or growth factor-like
      activity. This review also includes a consideration of selected background
      changes and typical strategies and markers used for evaluation of experimentally
      induced changes, including biopsy-based strategies designed to control for inter
      individual variability and minimize numbers of animals used.

PMID- 17443714
TI  - Atrazine and reproductive function: mode and mechanism of action studies.
AB  - Atrazine, a chlorotriazine herbicide, is used to control annual grasses and
      broadleaf weeds. In this review, we summarize our laboratory's work evaluating
      the neuroendocrine toxicity of atrazine (and related chlorotriazines) from an
      historic perspective. We provide the rationale for our work as we have endeavored
      to determine: 1) the underlying reproductive changes leading to the development
      of mammary gland tumors in the atrazine-exposed female rat; 2) the cascade of
      physiological events that are responsible for these changes (i.e., the mode of
      action for mammary tumors); 3) the potential cellular mechanisms involving
      adverse effects of atrazine; and 4) the range of reproductive alterations
      associated with this pesticide.

PMID- 17443715
TI  - High-throughput staining for the evaluation of fetal skeletal development in rats
      and rabbits.
AB  - Typical developmental toxicity studies require the assessment of fetal skeletal
      development. Regulatory guidelines require the assessment of bone ossification
      and indicate preferences for an assessment of both ossified bone as well as
      cartilaginous elements. Current manual methods to process fetuses for skeletal
      examination, whether single or double staining, are laborious and time consuming,
      and ultimately extend the time before study interpretations. There is a definite
      need for a quick and efficient, yet reliable, procedure to generate stained fetal
      skeletons for analysis. A non-automated high-throughput method for single and
      double staining rat and rabbit fetuses for skeletal evaluations is described,
      which results in excellent quality specimens ready for evaluations in
      approximately 3 days for rats and 7 days for rabbits.

PMID- 17443716
TI  - Evidence for axonemal distortion during the flagellar beat of Chlamydomonas.
AB  - In order to understand the working mechanism that governs the flagellar beat it
      is essential to know if the axoneme undergoes distortion during the course of the
      beat cycle. The rapid fixation method employed by Mitchell was able to preserve
      the waveform of Chlamydomonas flagella much as it appears during normal flagellar
      beating [Mitchell, Cell Motil Cytoskeleton 2003;56:120-129]. This conservation of
      the waveform suggests that the stress responsible for the production of bending
      is also trapped by the fixation procedure. Longitudinal sections of these well
      preserved flagella were used to document variations in the relative axonemal
      diameter. Sections aligned to the plane of bending, showing both the central pair
      microtubules and outer doublets, were examined for this purpose. Micrographs were
      selected that continuously showed both the outer doublets and the central pair
      from a straight region to a curved region of the flagellum. Axoneme diameters
      measured from these select micrographs showed an increase in relative diameter
      that averaged 39 nm greater at the crest of the bent region. This constituted a
      24% increase in the axoneme diameter in the bends. The transverse stress acting
      across the axoneme during bending was calculated from the Geometric Clutch
      computer model for a simulated Chlamydomonas-like flagellar beat. If we assume
      that this is representative of the transverse stress acting in a real flagellum,
      then the Young's modulus of the intact axoneme is approximately 0.02 MPa. The
      possibility that the distortion of the axoneme during the beat could play a
      significant role in regulating dynein function is discussed.

PMID- 17443717
TI  - Tachykinin receptor 1 variants associated with aggression in suicidal behavior.
AB  - Substance P is involved in the modulation of depression, anxiety, and suicidal
      related behaviors. We studied gene variants of Tachykinin Receptor 1 (TACR1
      rs3771810, rs3771825, rs726506, rs1477157) in 167 German suicide attempters
      (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline
      personality disorder n = 25), 92 Caucasian individuals who committed suicide and
      312 German healthy subjects. Single markers and haplotype analysis in relation to
      suicidal behaviors (suicide attempters/completers) did not reveal any significant
      association. The rarest rs3771825 T allele however showed a marginal association
      with higher Reactive Aggression scores on the Questionnaire for Measuring Factors
      of Aggression (FAF) (F = 9.86, df = 1; P = 0.0017). Haplotype analyses confirmed
      the finding. Violence or impulsivity of suicide attempt and State-Trait Anger
      Expression Inventory (STAXI) scores were not associated with gene variants. In
      conclusion, our study suggests that TACR1 gene variants have no major influence
      on suicidal behavior but may modulate aggression features.

PMID- 17443719
TI  - Head and neck squamous cell carcinoma as a model of oxidative-stress and cancer.

PMID- 17443718
TI  - Effect of time interval between surgery and preoperative chemoradiotherapy with 5
      fluorouracil or 5-fluorouracil and oxaliplatin on outcomes in rectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Preoperative chemoradiotherapy for locally advanced
      rectal cancer is now considered "standard of care." However, the optimal time
      interval for resection after neoadjuvant therapy is unknown. METHODS: Between
      11/90 and 11/04, 107 patients with rectal adenocarcinoma underwent preoperative
      chemo/RT at the University of Pennsylvania. Fifty-six percent had LAR and 40% had
      APR. Chemotherapy consisted of 5-FU/oxaliplatin in 28% and 5-FU in 72% of
      patients. All patients received preoperative RT. RESULTS: A longer time interval
      between chemo/RT and surgery was associated with tumor downstaging (OR 1.24, P =
      0.02). A longer time interval was not associated with: nodal downstaging (OR
      1.00, P = 0.98); pathologic complete response (PCR) (OR 0.97, P = 0.80);
      likelihood of performing an LAR (OR 0.90, P = 0.47); improved disease free
      survival (DFS), local control, or distant control (HR 1.05, P = 0.49; HR 1.14, P
      = 0.22; HR 1.06, P = 0.52, respectively). The PCR rate was 34.5% in the 5
      FU/oxaliplatin/radiation group, and 13.7% in the 5-FU/radiation group. If
      patients with microscopic CR were excluded, then the PCR rate for 5FU/OX was
      21.4% and for 5-FU was 12.2%. CONCLUSIONS: Time interval between surgery and
      chemo/RT appeared to have little effect on PCR or LAR rates. Patients receiving 5
      FU/oxaliplatin/RT had a high PCR rate. A prospective randomized trial to test
      superiority of 5 FU/oxaliplatin is warranted.

PMID- 17443720
TI  - Distribution and patterns of lymph nodes metastases and micrometastases in the
      mesorectum of rectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Facts buried in the mesorectum remain to be unveiled.
      This study investigated the number, size, and detailed distribution of lymph
      nodes metastases and micrometastases within the mesorectum of rectal cancer.
      METHODS: Thirty-one patients who underwent total mesorectal excision (TME) were
      treated with lymph node revealing solution to retrieve lymph nodes, which were
      submitted to hematoxylin and eosin (HE) examination and immunohistochemical (IHC)
      staining. RESULTS: The mean number of mesorectal nodes per case was 17.7. The
      mean size of metastatic, micrometastatic, and isolated tumor cells (ITC) harbored
      nodes was 5.2 mm, 4.5 mm, and 3.3 mm, respectively. Most of the metastatic
      (92.1%), micrometastatic and ITC-involved nodes (69.2%) were located along the
      superior rectal artery (SRA). Posterior-wall located tumor might spread along
      both sides of the mesorectum simultaneously (P = 0.34), while lateral-wall
      located tumor spread preferably to ipsolateral side versus contralateral side (P
      = 0.012). CONCLUSION: Most of the metastases and micrometastases positive lymph
      nodes were smaller than 5 mm and distributed along the SRA. The patterns of lymph
      nodes spread were related to the circumferential situation of tumor in the rectal
      wall. Surgical excision of the rectal cancer should completely remove the whole
      mesorectum, especially to avoid any damage of the mesorectum on tumor side.

PMID- 17443721
TI  - The incidence, indications and outcome for the non-operative management of breast
      cancer.
AB  - BACKGROUND AND OBJECTIVES: This study aimed to identify the proportion of
      patients with breast cancer who do not undergo primary operative treatment, to
      identify the reasons surgery is not performed, and to determine the outcome for
      this group of patients. METHODS: Data was obtained from the Bedford Breast Cancer
      Registry for all non-metastatic patients presenting between January 1990 and
      December 2004 who were initially treated non-operatively. Robust diagnostic,
      therapeutic, and follow-up data on all patients was collected prospectively
      during this period. RESULTS: One hundred and eighty-five out of 2110 episodes of
      breast cancer were treated non-operatively during this period. Sixty-eight
      percent of patients were unfit for surgery, 15% had inoperable tumours, and 17%
      refused surgical intervention. Median survival and 5-year survival rate for all
      non-operative patients were 3.7 years and 41.2%. Median survival for inoperable
      patients was 3.7 years, compared with 3.5 years for those unfit for surgery and
      4.2 years for those who refused surgery. The 5-year survival rate for patients
      refusing surgery was 43%, compared with 61% for a matched group of patients
      undergoing standard surgical therapy. CONCLUSIONS: This study provides useful
      data on the reasons for, and outcome of, the non-operative management of breast
      cancer.

PMID- 17443722
TI  - Alleviation of oxidative and nitrosative stress following curative resection in
      patient with oral cavity cancer.
AB  - BACKGROUND: Oxidative stress by reactive oxygen species (ROS) and nitrosative
      stress by reactive nitrogen species (RNS) are proven initiators and promoters in
      carcinogenesis. Elevated ROS/RNS with lowered antioxidants occur in patients with
      squamous cell carcinoma of oral cavity. Ours is the first study to evaluate the
      effect of curative resection on both oxidative and nitrosative stress in such
      patients. METHODS: This study was conducted on 24 cancer patients and with age-
      and sex-matched healthy controls. Lipid peroxidation products, nitric oxide (NO)
      products and ceruloplasmin (CPL) in plasma were measured before and after
      surgery. Similarly enzymatic antioxidants in erythrocytes and non-enzymatic
      antioxidants in plasma were measured. RESULTS: Statistically significant
      elevation of lipid peroxidation, NO products and CPL and depletion of
      antioxidants were found in cancer patients compared with controls. After curative
      surgical resection there was a statistically significant fall in oxidants and CPL
      coupled with a rise in antioxidants. CONCLUSIONS: Our results suggest that
      oxidative/nitrosative stress could play a significant role in oral cavity cancer
      (OCC) and that curative resection is effective in alleviating this
      oxidative/nitrosative burden. Significant mitigation of oxidative/nitrosative
      stress could indicate the completeness of resection since tumor forms the major
      source of oxidants.

PMID- 17443723
TI  - A multivariate analysis of adhesion molecules expression in assessment of
      colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Adhesion molecules are implicated in the progression
      of colorectal cancer (CRC). Despite the evidence of association between their
      expression and patients' prognosis, the data have not been examined
      simultaneously in a same study; thus, the relative clinical value remained
      largely unknown. The aim of this study was to identify the adhesion factors that
      display the most significant prognostic value for CRC patients to guide clinical
      decision-making regarding appropriate treatment. PATIENTS AND METHODS: We
      examined by immunohistochemistry, the expression of E-cadherin and its associated
      catenins, alpha(alpha)-catenin and beta(beta)-catenin, DCC, and CD44 and its
      partner, MT1-MMP in a series of 140 CRC tissues at intermediate Stage II and
      Stage III to determine their prognostic significance. RESULTS:
      Clinicopathological survey indicated an inverse relationship between E-cadherin
      expression and tumor differentiation, and an association between CD44 expression
      and venous invasion. Univariate and multivariate analyses showed that loss of
      expression of E-cadherin and CD44 significantly correlated to poor survival,
      especially in Stage II. Combination studies indicated that loss of E-cadherin and
      loss of CD44 had the worst impact on patient prognosis, particularly in colon
      cancer. CONCLUSION: Immunohistochemical staining of E-cadherin and CD44 may help
      to identify a subgroup of high-risk patients with Stage II CRC, especially in
      colon cancer, who may need intensive follow-up and appropriate therapeutic
      strategy.

PMID- 17443724
TI  - Rapidly enlarging thyroid neoplasm treated with embolization of thyroid arteries.

PMID- 17443725
TI  - Complex liver resection for a large intrahepatic cholangiocarcinoma in a
      Jehovah's witness: a strategy to avoid transfusion.
AB  - Although morbidity and mortality after liver resection have improved over the
      last two decades, complex liver resections still require perioperative blood
      transfusions. In this report, we describe the use of a combined left
      trisegmentectomy and caudate lobectomy, along with resection of the inferior vena
      cava, to treat a large intrahepatic cholangiocarcinoma in a Jehovah's Witness. To
      our knowledge, this is the first report of major liver resection for a large
      malignant tumor in this patient population. We also discuss the perioperative
      strategy and surgical technique we used to minimize blood loss and avoid
      transfusion. This approach could be a safe alternative for use in all patients
      with complex liver tumor, regardless of their religious beliefs, to reduce the
      risks and cost associated with blood transfusion.

PMID- 17443727
TI  - Prognostic impact of positive lymph node ratio in gastric carcinoma.
AB  - BACKGROUND AND OBJECTIVES: To evaluate the prognostic value of metastatic lymph
      node ratio in gastric carcinoma. METHODS: One hundred and sixty four patients who
      underwent D(2) dissection for gastric carcinoma at Ankara Oncology Hospital were
      reviewed retrospectively. The prognostic factors including Japanese
      classification, AJCC/UICC TNM classification and metastatic lymph node ratio (1
      10% and >10%) were evaluated in univariate and multivariate Cox regression
      analysis. RESULTS: The multivariate analysis showed that Borrmann classification,
      pN-category of AJCC/UICC classification and metastatic lymph node ratio were the
      most significant prognostic factors and a higher hazard ratio was obtained for
      metastatic lymph node ratio than pN category of AJCC/UICC classification (4.5 vs.
      11.4). When the metastatic ratio groups of 1-10% and >10% were subdivided into
      pN(1), pN(2) and pN(3) categories of the AJCC/UICC classification, there was no
      statistical difference between survival curves. When pN(1), pN(2) and pN(3)
      categories of the AJCC/UICC classification were subdivided into the ratio groups
      of 1-10% and >10%, the survival rate of ratio group 1-10% was better than ratio
      group >10%. CONCLUSION: With its simplicity and reproducibility, metastatic lymph
      node ratio can be used as a reliable prognostic indicator.

PMID- 17443726
TI  - MDR1 gene polymorphisms and risk of recurrence in patients with hepatocellular
      carcinoma after liver transplantation.
AB  - BACKGROUND AND OBJECTIVES: Recurrence of hepatocellular carcinoma (HCC) after
      liver transplantation (LT) remains a major cause of post-LT death. However,
      currently there is still lacking the markers to reliably predict recurrence. This
      study was undertaken to evaluate the association between three polymorphisms
      (C1236T, G2677A/T, C3435T) of Multidrug resistance 1 (MDR1) gene and the risk of
      recurrence after LT. METHODS: Genomic DNA of 99 HCC patients undergoing LT was
      extracted from peripheral blood lymphocytes and genotyping was performed using
      polymerase chain reaction-restriction fragment length polymorphism assay. Cox
      proportional hazard model was used to estimate the hazard ratios associated with
      polymorphisms. RESULTS: During a mean follow-up of 14.9 months, 49 patients
      experienced recurrence. The association between recurrence-free and 2677A carrier
      (carrying at least one variant A allele) was significant (P = 0.019). However, no
      significant association was observed in other polymorphisms. Patients with 2677A
      carrier conferred a 63% reduction in recurrence risk compared with 2677A non
      carrier (odds ratio: 0.374; 95% confidence interval: 0.177-0.788; P = 0.010). The
      median recurrence-free survival for 2677A carrier group was significantly longer
      than that for 2677A non-carrier group (44.2 vs. 10.5 months, P = 0.015).
      CONCLUSION: The polymorphism of MDR1 gene may be a valuable molecular marker for
      HCC recurrence after LT.

PMID- 17443728
TI  - Ovarian metastasis from colorectal cancer: prognostic value of radical
      oophorectomy.
AB  - BACKGROUND: Ovarian metastases from primary colorectal cancer occur in 3-8% of
      female patients. The aim of this study was to assess the prognostic value of
      radical oophorectomy for ovarian metastasis from colorectal cancer. PATIENTS AND
      METHODS: From our series of 859 patients operated for colorectal cancer from 1982
      to 2005 ten patients with isolated ovarian metastasis were retrieved. Ovarian
      colorectal metastasis diagnosis was confirmed by pathology revision. Overall and
      disease-free survival after radical oophorectomy for metastases were assessed and
      compared with literature data. RESULTS: The median follow-up from ovarian
      metastases resection was 36 months (range 194-14). Survival analysis showed that
      survival rate after ovarian metastasectomy was 100% at 1 year and 80% at 5 years
      of follow up. CONCLUSION: Our study, although limited by a relatively short
      follow-up and small sample size, shows that bilateral oophorectomy for ovarian
      metastasis from colorectal cancer has a good impact on disease-free and overall
      survival.

PMID- 17443729
TI  - The cryosurgical treatment of chondroblastoma of bone: long-term oncologic and
      functional results.
AB  - BACKGROUND: Chondroblastoma of bone is a rare tumor that occurs most often in the
      epiphysis or apophysis of long bones. This benign tumor sometimes shows
      aggressive or malignant behaviour, and rarely metastases occur. Since wide
      resection often leads to growth impairment, intra-lesional curettage followed by
      an adjuvant therapy is developed to decrease the negative effects on growth and
      function without increased recurrence rates. PATIENTS AND METHODS: Between 1980
      and 2001, 18 patients were treated for chondroblastoma of bone. Since 1989
      cryosurgery has been used as an adjuvant treatment. The functional and oncologic
      results at follow-up were studied. RESULTS: Four patients were treated with
      curettage, and four with wide resection without adjuvant therapy. One patient
      developed a local recurrence and distant metastases. Ten patients were treated
      with curettage and cryosurgery. One patient developed a local recurrence 6 years
      later that was treated with curettage and cryosurgery again. No serious
      complications from cryosurgery occurred and the functional results at follow-up
      were excellent [mean MSTS score at follow-up 29]. CONCLUSIONS: Chondroblastoma of
      bone is a benign tumor with a relatively high recurrence rate. The local
      recurrence rates can be decreased with cryosurgery as a local adjuvant therapy
      with excellent functional results.

PMID- 17443730
TI  - CLIC4, skin homeostasis and cutaneous cancer: surprising connections.
AB  - Chloride intracellular channel 4 (CLIC4) is a putative chloride channel for
      intracellular organelles. CLIC4 has biological activities in addition to or
      because of its channel activity. In keratinocytes, CLIC4 resides in the
      mitochondria and cytoplasm, and CLIC4 gene expression is regulated by p53, TNF
      alpha, and c-Myc. Cytoplasmic CLIC4 translocates to the nucleus in response to
      cellular stress conditions including DNA damage, metabolic inhibition,
      senescence, and exposure to certain trophic factors such as TNF-alpha and LPS.
      Nuclear translocation is associated with growth arrest or apoptosis, depending on
      the level of expression. In the nucleus CLIC4 interacts with several nuclear
      proteins as demonstrated by yeast two-hybrid screening and co
      immunoprecipitation. Nuclear CLIC4 appears to act on the TGF-beta pathway, and
      TGF-beta also causes CLIC4 nuclear translocation. In human and mouse cancer cell
      lines, CLIC4 levels are reduced, and CLIC4 is excluded from the nucleus. CLIC4
      soluble or membrane-inserted status is dependent on redox state, and redox
      alterations in cancer cells could underly the defect in nuclear translocation.
      CLIC4 is reduced and excluded from the nucleus of many human epithelial
      neoplasms. Paradoxically, CLIC4 is reciprocally upregulated in tumor stroma in
      conjunction with the expression of alpha-smooth muscle actin in the fibroblast to
      myofibroblast transition. Overexpression of CLIC4 in cancer cells inhibits tumor
      growth in vivo. Conversely, overexpression of CLIC4 in tumor stromal cells
      stimulates tumor growth in vivo. Thus, CLIC4 participates in normal and
      pathological processes and may serve as a useful target for therapies in
      disturbances of homeostasis and neoplastic transformation.

PMID- 17443731
TI  - Combined brief psychosexual intervention after mastectomy: effects on sexuality,
      body image, and psychological well-being.
AB  - BACKGROUND: Mastectomy poses a severe threat to body image and sexuality,
      interfering with the psychological well-being of both the patient and her
      partner. Although many psychotherapeutic approaches have been assessed and found
      effective in such patients, few studies have assessed couple or sex therapy in
      mastectomy patients. METHODS: We report on a structured combination of brief
      couples and sex therapy (CBPI) used in 20 women with in situ breast cancer and
      mastectomy and their partners. An equal number of mastectomy patients were used
      as controls. RESULTS: CBPI patients showed significant improvement in depression
      and state anxiety scores, as well as in body image, satisfaction with
      relationship, presumed attractiveness to their partner, orgasm frequency and
      communicating their desire. DISCUSSION/CONCLUSIONS: CBPI can be used as an
      effective alternative to individual or group psychotherapy for mastectomy
      patients.

PMID- 17443732
TI  - Minimal residual disease, the rationale for adjuvant therapy in epithelial
      malignancies.

PMID- 17443733
TI  - I-123-guided excision of metastatic papillary thyroid cancer.
AB  - The use of a gamma probe for intraoperative localization of a cervical lymph
      node, which contained recurrent metastatic papillary thyroid cancer, facilitated
      a radio-guided minimally invasive outpatient surgical procedure and resulted in
      complete excision of clinically occult disease. The technique raises the issue of
      whether nonpalpable regional node recurrences should be locally excised, removed
      in a formal modified neck dissection, or treated with therapeutic doses of I-131.

PMID- 17443734
TI  - Organ-based subspecialization in surgical oncology: fragmentation as a path to
      progress?

PMID- 17443735
TI  - Hepatectomy and lung radiofrequency ablation for hepatic and subsequent pulmonary
      metastases from colorectal carcinoma.
AB  - BACKGROUND: Lung radiofrequency ablation (RFA) is a relatively safe procedure and
      may have a useful role in the management of non-surgical candidates with
      colorectal pulmonary metastases. METHODS: This study consisted of 30 patients,
      who had previously undergone hepatectomy for colorectal liver metastases and
      subsequently developed pulmonary metastases, which were then treated with lung
      RFA. Lung RFA was performed percutaneously under local anesthesia and conscious
      sedation. The primary aim of this article was to demonstrate the survival outcome
      in this particular patient population after lung RFA. The secondary aim was to
      assess the prognostic indicators for survival after lung RFA. RESULTS: The median
      survival after lung RFA was 32 months, with 3-year survival rate of 45%. The
      following four factors were found to significantly influence survival in
      univariate analysis: size of the largest pulmonary metastasis (P = 0.032),
      proximity of metastases to major pulmonary vessels (P = 0.003), pre-lung RFA CEA
      levels (P = 0.013) and post-lung RFA CEA levels (P = 0.022). CONCLUSIONS: Lung
      RFA may have a useful role in the management of non-surgical candidates with
      colorectal pulmonary metastases.

PMID- 17443736
TI  - Surgical lymphedema and its assessment.

PMID- 17443737
TI  - "Wide local ablation" of localized breast cancer using high intensity focused
      ultrasound.
AB  - BACKGROUND AND OBJECTIVE: High intensity focused ultrasound (HIFU) is a non
      invasive technique for tumor ablation. The goal of this study was to investigate
      the feasibility of performing wide local ablation using ultrasound-guided HIFU in
      the treatment of patients with localized breast cancer. METHODS: Twenty-three
      patients with histologically proven breast cancer were enrolled in this
      prospective clinical trial. They underwent HIFU treatment for breast cancer
      including the tumor and 1.5-2.0 cm normal breast tissue surrounding the tumor,
      followed by modified mastectomy 1-2 weeks after HIFU. Radiological examination,
      histological, and terminal deoxynucleotidyl transferase-mediated nick end
      labeling (TUNEL) methods were performed to evaluate therapeutic effects in the
      treated region. RESULTS: Thermal ablation was confirmed in all 23 patients. It
      included tumor and normal breast tissue surrounding the tumor. Mean values of the
      largest parallel and perpendicular dimensions, and volume of HIFU lesions in
      excised breasts were significantly larger than those of the targeted tumors
      respectively (P < 0.001). Hematoxylin and eosin (H & E) staining showed clear
      evidence of complete coagulation necrosis in the treated regions. However, no
      apoptotic cells were detected in either treated tumor or normal breast tissue.
      CONCLUSION: As a non-invasive therapy, ultrasound-guided HIFU can induce wide
      local ablation in the treatment of patients with localized breast cancer.

PMID- 17443739
TI  - Combined liver and inferior vena cava resection for hepatic malignancy.
AB  - OBJECTIVE: The experience from a single center, in combined liver and inferior
      vena cava (IVC) resection for liver tumors, is presented. METHODS: Twelve
      patients underwent a combined liver resection with IVC replacement. The median
      age was 45 years (range 35-67 years). Resections were carried out for
      hepatocellular carcinoma (n = 4), colorectal metastases (n = 6), and
      cholangiocarcinoma (n = 2). Liver resections included eight right lobectomies and
      four left trisegmentectomies. The IVC was reconstructed with ringed Gore-Tex tube
      graft. RESULTS: No perioperative deaths were reported. The median operative blood
      transfusion requirement was 2 units (range 0-12 units) and the median operative
      time was 5 hr. Median hospital stay was 10 days (range 8-25 days). Three patients
      had evidence of postoperative liver failure, resolved with supportive management.
      Two patients developed bile leaks, resolved conservatively. With a median follow
      up of 24 months, all vascular reconstructions were patent and no evidence of
      graft infection was documented. CONCLUSIONS: Aggressive surgical management of
      liver tumors, offer the only hope for cure or palliation. We suggest that liver
      resection with vena cava replacement may be performed safely, with acceptable
      morbidity, by specialized surgical teams.

PMID- 17443738
TI  - Apoptosis and chemo-resistance in colorectal cancer.
AB  - Systemic chemotherapy plays an integral part in treating advanced colorectal
      cancer. However 50% of patients respond poorly or have disease progression due to
      resistance to chemotherapeutic agents. This article reviews the pathways that
      regulate apoptosis, apoptotic mechanisms through which chemotherapeutic agents
      mediate their effect and how deregulation of apoptotic proteins may contribute to
      chemo-resistance. Also discussed are potential therapeutic strategies designed to
      target these proteins and thereby improve response rates to chemotherapy in
      colorectal cancer.

PMID- 17443740
TI  - Radiofrequency ablation for pulmonary metastases: a therapy in evolution.

PMID- 17443741
TI  - Targeting Bcl-X(L) for prevention and therapy of skin cancer.
AB  - Apoptosis plays an important role in skin carcinogenesis. Bcl-X(L), an
      antiapoptotic Bcl-2 family member, is a key regulator in the process. Aberrant
      expression of Bcl-X(L) allows cells carrying mutations to survive and propagate.
      Overexpression of Bcl-X(L) is correlated with tumor malignancy and invasion.
      Importantly, deregulation of Bcl-X(L) confers drug resistance to chemotherapy.
      Therefore, targeting Bcl-X(L) in combination with conventional chemotherapy is a
      promising way to pursue cancer chemotherapy. Several compounds targeting Bcl-X(L)
      expression or function have shown their potential in chemoprevention and of
      chemotherapy of cancer.

PMID- 17443742
TI  - Vascular reconstruction with the superficial femoral vein following major
      oncologic resection.
AB  - INTRODUCTION: Involvement of critical vascular structures has historically been
      considered a contraindication to tumor resection. This study describes outcomes
      following radical oncologic resection with concomitant resection of critical
      vascular structures and reconstruction with the superficial femoral vein (SFV).
      METHODS: All patients undergoing radical oncologic resection requiring resection
      of major vascular structures and concomitant reconstruction using the SFV as
      conduit were retrospectively reviewed. Primary outcomes were surgical morbidity
      and mortality; secondary measures included long-term patency and oncologic
      outcomes. RESULTS: Seven patients were included. There were three retroperitoneal
      and two groin sarcomas, and two squamous cell carcinomas metastatic to groin
      lymph nodes. No perioperative mortality occurred. Five patients experienced minor
      morbidity. One vein graft in a patient with pre-existing chronic deep venous
      thrombosis (DVT) occluded post-operatively. No subsequent long-term venous or
      arterial graft occlusions occurred (median 20.2 months, range 9.0-49.7). Two
      patients died of tumor recurrence during follow-up. CONCLUSIONS: Resection of
      tumors involving critical vascular structures is feasible. The SFV conduit is a
      versatile option for major vascular reconstruction, providing good long-term
      patency rates with acceptable morbidity and mortality. Vascular resection and
      reconstruction with the SFV offers another technique to provide limb-sparing
      surgery in patients traditionally offered only amputation, while providing
      favorable oncologic outcomes.

PMID- 17443743
TI  - Should adjuvant radiotherapy to the supraclavicular fossa be routinely given in
      patients with breast conservative treatment?
AB  - BACKGROUND: To analyze the overall outcome, supraclavicular fossa (SCF)
      recurrence rate, and pattern of failure in breast cancer patients treated with
      conservative surgery and adjuvant radiotherapy excluding SCF treatment. METHODS:
      A total of 143 patients were enrolled in the study. Ninety-two percent of
      patients were stages I and II, and 8% were stage III. The median age was 44
      years, and 31% of patients were </=40 years old. Radiotherapy was delivered to
      the ipsilateral breast excluding the SCF. RESULTS: The 5-year overall survival
      rate of the cohort was 95%, and disease-free survival rate was 91%. The
      cumulative incidence of SCF recurrence was 18% in patients with involved axillary
      nodes (N) >/= 4, and 0.8% in patients with N < 4. The 5-year SCF-recurrence-free
      survival in patients with N >/= 4 and N < 4 was 80% and 99%, respectively (P <
      0.001). N >/= 4 was the only independent predictor for locoregional control (P =
      0.045), disease-free survival (P = 0.001), and overall survival (P = 0.008) in
      multivariate analysis. CONCLUSIONS: Women with N >/= 4 have a significantly
      higher risk of SCF recurrence and poorer survival. The SCF might be safely spared
      in patients with N < 4, but should be routinely included in the radiotherapy
      design for those with N >/= 4.

PMID- 17443744
TI  - Clinical impact of the surgical margin status in hepatectomy for solitary mass
      forming type intrahepatic cholangiocarcinoma without lymph node metastases.
AB  - BACKGROUND AND OBJECTIVES: The clinical impact of the surgical margin status in
      macroscopic curative hepatectomy for intrahepatic cholangiocarcinoma (ICC) has
      not yet been fully investigated. METHODS: The data of 57 consecutive patients
      with mass-forming (MF) type ICC who underwent macroscopic curative hepatectomy
      during a 10-year period were retrospectively examined, and the relationship
      between the surgical margin status and patient survival was analyzed. RESULTS:
      Lymph node metastases were found to be independently associated with poor
      survival. The overall 5-year survival rates and the median survival term in the
      38 patients without lymph node metastases were 56.8% and 62 months, respectively.
      Among these 38 patients, the survival rate was better in the negative surgical
      margin group as compared with that in the positive surgical margin group.
      However, there was no statistically significant difference between the narrow and
      wide surgical margin groups. CONCLUSIONS: Negative surgical margin had a definite
      favorable impact on the survival of patients with a solitary ICC without lymph
      node metastases. Surgery should be conducted in patients without lymph node
      metastases even if a wide surgical margin cannot be obtained, but careful
      attention should be paid not to expose tumors during hepatic dissection.

PMID- 17443745
TI  - A role for cyclooxygenase-2 in ultraviolet light-induced skin carcinogenesis.
AB  - Nonmelanoma skin cancer is the most prevalent cancer in the United States and its
      incidence is on the rise. These cancers generally arise on sun-exposed areas of
      the body and the ultraviolet (UV) B spectrum of sunlight has been clearly
      identified as the major carcinogen responsible for skin cancer development.
      Besides inducing DNA damage directly, UV exposure of the skin induces the
      expression of the enzyme cyclooxygenase-2 (COX-2), which catalyzes the first step
      in the conversion of arachidonic acid to prostaglandins, the primary product in
      skin being prostaglandin E(2) (PGE(2)). COX-2 has been shown to be overexpressed
      in premalignant lesions as well as in nonmelanoma skin cancers in both humans and
      mice chronically exposed to UV. Through the use of COX-2-selective inhibitors and
      COX-2 knockout mice, it has been shown that UV-induced COX-2 expression plays a
      major role in UV-induced PGE(2) production, inflammation, edema, keratinocyte
      proliferation, epidermal hyperplasia, and generation of a pro-oxidant state
      leading to oxidative DNA damage. Chronic exposure to UV leads to chronic up
      regulation of COX-2 expression and chronic inflammation along with the
      accumulation of DNA damage and mutations, all of which combine to induce
      malignant changes in epidermal keratinocytes and skin cancers. Both inhibition of
      COX-2 activity and reduction in COX-2 expression by genetic manipulations
      significantly reduce, while overexpression of COX-2 in transgenic mice
      significantly increases UV-induced skin carcinogenesis. Together these studies
      demonstrate that COX-2 expression/activity is critical to the development of UV
      related nonmelanoma skin cancers.

PMID- 17443746
TI  - Surgical management of carcinoma of the cervical esophagus.
AB  - OBJECTIVES: The aim of the present study was to clarify the clinicopathological
      characteristics, reconstruction methods after resection, and prognosis of
      cervical esophageal squamous cell carcinoma. METHODS: Seventy-four with squamous
      cell carcinomas of the cervical esophagus not previously treated who underwent
      cervical esophagectomy or total esophagectomy with or without laryngectomy were
      retrospectively analyzed. RESULTS: The operative morbidity and in-hospital
      mortality rates were 34% (25 patients) and 4% (3 patients), respectively.
      Alimentary continuity was achieved with free jejunal transfer (50 patients),
      gastric pull-up (19 patients), and other procedures (5 patients). The frequencies
      of postoperative complications and death did not differ between free jejunal
      transfer and gastric pull-up. The overall 3- and 5-year survival rates were 42%
      and 33%, respectively. The significant clinicopathological factors affecting
      survival were patient gender, high T factor, lymph node involvement, palpable
      cervical lymph nodes, vocal cord paralysis, lymphatic invasion, and extracapsular
      invasion. The pattern of first failure was most often locoregional (82%, 36
      patients). CONCLUSION: The choice of free jejunal transfer or gastric pull-up for
      reconstruction after surgical resection of cervical esophageal carcinoma depends
      on the degree of tumor extension. Adverse factors affecting survival should be
      considered when candidates for the surgery are selected.

PMID- 17443747
TI  - Prevention of surgical site infection after breast cancer surgery by targeted
      prophylaxis antibiotic in patients at high risk of surgical site infection.
AB  - OBJECTIVE: We previously showed that previous chemotherapy and immediate breast
      reconstruction were associated with an increased risk of surgical site infection
      (SSI) in patients undergoing breast cancer surgery. The present before-after
      study evaluated a preventive strategy for high-risk patients. PATIENTS AND
      METHODS: We compared the incidence of SSI in two prospective observational
      cohorts of patients underwent clean procedure in curative intent for a-biopsy
      proven breast cancer: a historical cohort followed before implementation of a
      preventive strategy and a second cohort followed thereafter. The strategy
      consisted of identifying patients at risk of SSI and prophylaxis administration
      of cefuroxime to those patients. The impact of our strategy was analyzed using a
      logistic regression model adjusted for potential confounders. RESULTS: SSI
      incidence was estimated at 19/542 (3.5%) before preventive strategy versus 2/247
      (0.8%) thereafter (crude odds ratio (OR) 0.22 confidence interval [95% CI 0.05
      0.97], P = 0.03). After adjustment for confounders (breast reconstruction,
      previous breast surgery, and duration of surgery), our preventive strategy
      reduced the risk of SSI by 81% (adjusted OR 0.19 [95% CI 0.04-0.85], P = 0.03).
      CONCLUSION: These results showed that antibiotic prophylaxis is beneficial for
      patients at high-risk of WI after breast cancer surgery. Randomized controlled
      trials should now confirm these findings.

PMID- 17443748
TI  - Sunlight and skin cancer: lessons from the immune system.
AB  - The ultraviolet (UV) radiation in sunlight induces skin cancer development. Skin
      cancer is the most common form of human neoplasia. Estimates suggest that in
      excess of 1.5 million new cases of skin cancer (www.cancer.org/statistics) will
      be diagnosed in the United States this year. Fortunately, because of their highly
      visible location, skin cancers are more rapidly diagnosed and more easily treated
      than other types of cancer. Be that as it may, approximately 10,000 Americans a
      year die from skin cancer, and the cost of treating skin cancer in the United
      States (both melanoma and non-melanoma skin cancer) is estimated to be in excess
      of $2.9 billion a year. In addition to causing skin cancer, UV radiation is also
      immune suppressive. In fact, data from studies with both experimental animals and
      biopsy proven skin cancer patients suggest that there is an association between
      the immune suppressive effects of UV radiation and its carcinogenic potential.
      Recent studies in my laboratory have focused on understanding the initial
      molecular events that induce immune suppression. We made two novel observations:
      first UV-induced keratinocyte-derived platelet activating factor plays a role in
      the induction of immune suppression. Second, cis-urocanic acid, a skin-derived
      immunosuppressive compound mediates immune suppression by binding to serotonin
      receptors on target cells. Recent findings suggest that blocking the binding of
      these compounds to their receptors not only inhibits UV-induced immune
      suppression but it also interferes with skin cancer induction.

PMID- 17443749
TI  - Physical activity for osteoarthritis management: a randomized controlled clinical
      trial evaluating hydrotherapy or Tai Chi classes.
AB  - OBJECTIVE: To determine whether Tai Chi or hydrotherapy classes for individuals
      with chronic symptomatic hip or knee osteoarthritis (OA) result in measurable
      clinical benefits. METHODS: A randomized controlled trial was conducted among 152
      older persons with chronic symptomatic hip or knee OA. Participants were randomly
      allocated for 12 weeks to hydrotherapy classes (n = 55), Tai Chi classes (n =
      56), or a waiting list control group (n = 41). Outcomes were assessed 12 and 24
      weeks after randomization and included pain and physical function (Western
      Ontario and McMaster Universities Osteoarthritis Index), general health status
      (Medical Outcomes Study Short Form 12 Health Survey [SF-12], version 2),
      psychological well-being, and physical performance (Up and Go test, 50-foot walk
      time, timed stair climb). RESULTS: At 12 weeks, compared with controls,
      participants allocated to hydrotherapy classes demonstrated mean improvements
      (95% confidence interval) of 6.5 (0.4, 12.7) and 10.5 (3.6, 14.5) for pain and
      physical function scores (range 0-100), respectively, whereas participants
      allocated to Tai Chi classes demonstrated improvements of 5.2 (-0.8, 11.1) and
      9.7 (2.8, 16.7), respectively. Both class allocations achieved significant
      improvements in the SF-12 physical component summary score, but only allocation
      to hydrotherapy achieved significant improvements in the physical performance
      measures. All significant improvements were sustained at 24 weeks. In this almost
      exclusively white sample, class attendance was higher for hydrotherapy, with 81%
      attending at least half of the available 24 classes, compared with 61% for Tai
      Chi. CONCLUSION: Access to either hydrotherapy or Tai Chi classes can provide
      large and sustained improvements in physical function for many older, sedentary
      individuals with chronic hip or knee OA.

PMID- 17443750
TI  - Stereoselective synthesis of ferrocene-based C2-symmetric diphosphine ligands:
      application to the highly enantioselective hydrogenation of alpha-substituted
      cinnamic acids.

PMID- 17443751
TI  - Palladium-catalyzed synthesis of substituted cycloheptane-1,4-diones by an
      asymmetric ring-expanding allylation (AREA).

PMID- 17443752
TI  - Direct electrochemical characterization of archaeal thioredoxins.

PMID- 17443753
TI  - Ordered three-dimensional arrays of monodispersed Mn3O4 nanoparticles with a core
      shell structure and spin-glass behavior.

PMID- 17443754
TI  - Multiple reversible protonation of polyoxoanion surfaces: direct observation of
      dynamic structural effects from proton transfer.

PMID- 17443755
TI  - Asymmetric assembly of aromatic rings to produce tetra-ortho-substituted axially
      chiral biaryl phosphorus compounds.

PMID- 17443756
TI  - Exciton accumulation in pi-conjugated wires encapsulated by light-harvesting
      macrocycles.

PMID- 17443757
TI  - Molecular printboards as a general platform for protein immobilization: a
      supramolecular solution to nonspecific adsorption.

PMID- 17443758
TI  - A white-light-emitting borate-based inorganic-organic hybrid open framework.

PMID- 17443759
TI  - Amino acid phosphoramidate nucleotides as alternative substrates for HIV-1
      reverse transcriptase.

PMID- 17443760
TI  - Synthesis of the carbocyclic core of zoanthenol: implementation of an unusual
      acid-catalyzed cyclization.

PMID- 17443761
TI  - Chirality enrichment through the heterorecognition of enantiomers in an achiral
      coordination host.

PMID- 17443762
TI  - Tracking the chiral recognition of adsorbed dipeptides at the single-molecule
      level.

PMID- 17443763
TI  - A supramolecular-hydrogel-encapsulated hemin as an artificial enzyme to mimic
      peroxidase.

PMID- 17443764
TI  - Caenorhabditis elegans mitochondrial mutants as an investigative tool to study
      human neurodegenerative diseases associated with mitochondrial dysfunction.
AB  - In humans, well over one hundred diseases have been linked to mitochondrial
      dysfunction and many of these are associated with neurodegeneration. At the root
      of most of these diseases lay ineffectual energy production, caused either by
      direct or indirect disruption to components of the mitochondrial electron
      transport chain. It is surprising then to learn that, in the nematode
      Caenorhabditis elegans, a collection of mutants which share disruptions in some
      of the same genes that cause mitochondrial pathogenesis in humans are in fact
      long-lived. Recently, we resolved this paradox by showing that the C. elegans
      "Mit mutants" only exhibit life extension in a defined window of mitochondrial
      dysfunction. Similar to humans, when mitochondrial dysfunction becomes too severe
      these mutants also exhibit pathogenic life reduction. We have proposed that life
      extension in the Mit mutants occurs as a by-product of compensatory processes
      specifically activated to maintain mitochondrial function. We have also proposed
      that similar kinds of processes may act to delay the symptomatic appearance in
      many human mitochondrial-associated disorders. In the present report, we describe
      our progress in using the Mit mutants as an investigative tool to study some of
      the processes potentially employed by human cells to offset pathological
      mitochondrial dysfunction.

PMID- 17443765
TI  - Biosensor development in Russia.
AB  - The review summarizes the current Russian research in the field of biological
      sensors for detection of carbohydrates, alcohols, medicines, enzyme inhibitors,
      toxicants, heavy metal ions, as well as viruses and microbial cells. Some of the
      presented works describe the analytical parameters of biosensors; other
      publications provide a basis for their development. The review covers mainly
      publications that have appeared over the past 10 years. As a whole, the collected
      material gives an idea of the main tendencies of biosensor development in Russia.
      The review is not meant to be comprehensive but highlights the major trends in
      this field in the last decade.

PMID- 17443767
TI  - Subcellular compartmentalization of aromatase is sexually dimorphic in the adult
      zebra finch brain.
AB  - The vertebrate brain is a source of estrogen (E) via the expression of aromatase
      (E-synthase). In the zebra finch (Taeniopygia guttata), despite documented
      dimorphisms in E-action, no differences are detectable in circulating E, or the
      neural levels of aromatase transcription, activity, or somal protein expression.
      Studies of aromatase expression at the light- and electron-microscope levels
      reveal greater numbers of fibers and presynaptic boutons in adult males relative
      to females. We assayed aromatase activity and content in synaptosomes and
      microsomes from the anterior [containing lMAN and Area X (males)] and posterior
      telencephalon (containing HVC and RA) of adult birds. In contrast to non-song
      birds and mammals, both cell fractions contain abundant aromatase measurable in
      terms of activity (enzyme assays) and content (Western blots) with minimal
      enrichment in microsomes. From brain homogenates of identical concentration,
      aromatase activity was higher in the synaptosomal relative to the microsomal
      fraction, in males relative to females, and in the posterior compared to anterior
      telencephalon. These effects were driven by high levels of synaptosomal aromatase
      in the male posterior telencephalon. These data suggest that males possess more
      aromatase per presynaptic bouton, or a greater number of aromatase-containing
      presynaptic boutons than females in the posterior telencephalon. Further, the
      present report reveals synaptic aromatization as a considerable source of E in
      the zebra finch brain, and supports the idea that telencephalic synapses in and
      around the adult male song production nuclei may be exposed to higher levels of E
      compared to the female brain.

PMID- 17443768
TI  - Serotonin decreases generation of dopaminergic neurons from mesencephalic
      precursors via serotonin type 7 and type 4 receptors.
AB  - Inductive signals mediating the differentiation of neural precursors into
      serotonergic (5-HT) or dopaminergic neurons have not been clarified. We have
      recently shown that in cell aggregates obtained from rat mesencephalic
      precursors, reduction of serotonin levels induces a marked increase in generation
      of dopaminergic neurons. In the present study we treated rat neurospheres with
      antagonists of the main subtypes of 5-HT receptors, 5-HT transport inhibitors, or
      5-HT receptor agonists, and studied the effects on generation of dopaminergic
      neurons. Cultures treated with Methiothepin (5-HT(1,2,5,6,7) receptor
      antagonist), the 5-HT(4) receptor antagonist GR113808;67:00-.or the 5-HT(7)
      receptor antagonist SB 269970 showed a significant increase in generation of
      dopaminergic cells. Treatment with the 5-HT(1B/1D) antagonist GR 127935, the 5
      HT(2) antagonist Ritanserin, the 5-HT transporter inhibitor Fluoxetine, the
      dopamine and norepinephrine transport inhibitor GBR 12935, or with both
      inhibitors together, or 5-HT(4) or 5-HT(7) receptor agonists induced significant
      decreases in generation of dopaminergic cells. Cultures treated with WAY100635 (5
      HT(1A) receptor antagonist), the 5-HT(3) receptor antagonist Ondasetron, or the 5
      HT(6) receptor antagonist SB 258585 did not show any significant changes.
      Therefore, 5-HT(4) and 5-HT(7) receptors are involved in the observed serotonin
      induced decrease in generation of dopaminergic neurons from proliferating
      neurospheres of mesencephalic precursors. 5-HT(4) and 5-HT(7) receptors were
      found in astrocytes and serotonergic cells using double immunolabeling and laser
      confocal microscopy, and the glial receptors appeared to play a major role.

PMID- 17443769
TI  - Delta expression in post-mitotic neurons identifies distinct subsets of adult
      specific lineages in Drosophila.
AB  - The Drosophila ventral nerve cord is comprised of numerous neuronal lineages,
      each derived from a stereotypically positioned neuroblast (NB). At the embryonic
      stage the unique identities of each NB, and several of their neuronal progeny,
      are well characterized by spatial and temporal expression patterns of molecular
      markers. These patterns of expression are not preserved at the larval stage and
      thus the identity of adult-specific lineages remains obscure. Recent clonal
      analysis using MARCM has identified 24 adult-specific lineages arising from
      thoracic NBs at the larval stage. In this study, we have explored a role for the
      Delta protein in development of the post-embryonic Drosophila ventral nerve cord.
      We find that Delta expression identifies 7 of the 24 adult-specific lineages of
      the thoracic ganglia by being highly enriched in clusters of newly born post
      mitotic neurons and their neurite bundles. The Delta lineages constitute the
      majority of bundles projecting to the ventral neuropil, consistent with a role in
      processing leg sensory information. Targeted knockdown of Delta in neurons using
      RNAi results in significantly decreased leg chemosensory response and a
      relatively unaffected leg mechanosensory response. Delta RNAi knockdown in Delta
      lineages also gives a more diffuse bundle terminal morphology while the overall
      path-finding of neurite bundles is unaffected. We also identify a male-specific
      Delta lineage in the terminal abdominal ganglia, implicating a role for Delta in
      development of sexually dimorphic neural networks. Examples of Delta-expressing
      neurites contacting Notch-expressing glia are also seen, but are not common to
      all Delta lineages. Altogether, these data reveal a fundamental pattern of Delta
      expression that is indicative of an underlying developmental program that confers
      identity to adult lineage neurons.

PMID- 17443770
TI  - Developmental and dominance-associated differences in mushroom body structure in
      the paper wasp Mischocyttarus mastigophorus.
AB  - Primitively eusocial paper wasps exhibit considerable plasticity in their
      division of labor. Dominance interactions among nest mates play a strong role in
      determining the task performance patterns of adult females. We asked whether
      dominance status and task performance differences were associated with the
      development of subregions of the mushroom bodies (MB) of female Mischocyttarus
      mastigophorus queens and workers. We found that the MB calycal neuropils were
      better developed (relative to the Kenyon cell body layer) in the dominant females
      that spent more time on the nest. Increased MB calyx development was more
      strongly associated with social dominance than with high rates of foraging. The
      MB of queens resembled those of dominant workers. The results suggest that social
      interactions are particularly relevant to M. mastigophorus females' cognition. By
      examining the MB of newly emerged females, we also found evidence for significant
      age-related changes in MB structure.

PMID- 17443771
TI  - Neuropilin 2/semaphorin 3F signaling is essential for cranial neural crest
      migration and trigeminal ganglion condensation.
AB  - In the head of vertebrate embryos, neural crest cells migrate from the neural
      tube into the presumptive facial region and condense to form cranial ganglia and
      skeletal elements in the branchial arches. We show that newly formed neural folds
      and migrating neural crest cells express the neuropilin 2 (npn2) receptor in a
      manner that is highly conserved in amniotes. The repulsive npn2 ligand semaphorin
      (sema) 3F is expressed in a complementary pattern in the mouse. Furthermore, mice
      carrying null mutations for either npn2 or sema3F have abnormal cranial neural
      crest migration. Most notably, "bridges" of migrating cells are observed crossing
      between neural crest streams entering branchial arches 1 and 2. In addition,
      trigeminal ganglia fail to form correctly in the mutants and are improperly
      condensed and loosely organized. These data show that npn2/sema3F signaling is
      required for proper cranial neural crest development in the head.

PMID- 17443772
TI  - Low sex steroids, high steroid receptors: Increasing the sensitivity of the
      nonreproductive brain.
AB  - Male aggressive behavior is generally regulated by testosterone (T). In most
      temperate breeding males, aggressive behavior is only expressed during the
      reproductive period. At this time circulating T concentrations, brain steroid
      receptors, and steroid metabolic enzymes are elevated in many species relative to
      the nonreproductive period. Many tropical birds, however, display aggressive
      behavior both during the breeding and the nonbreeding season, but plasma levels
      of T can remain low throughout the year and show little seasonal fluctuation.
      Studies on the year-round territorial spotted antbird (Hylophylax n. naevioides)
      suggest that T nevertheless regulates aggressive behavior in both the breeding
      and nonbreeding season. We hypothesize that to regulate aggressive behaviors
      during the nonbreeding season, when T is at its minimum, male spotted antbirds
      increase brain sensitivity to steroids. This can be achieved by locally up
      regulating androgen receptors (ARs), estrogen receptors (ERs), or the enzyme
      aromatase (AROM) that converts T into estradiol. We therefore compared mRNA
      expression of AR, ERalpha, and AROM in free- living male spotted antbirds across
      reproductive and nonreproductive seasons in two brain regions known to regulate
      both reproductive and aggressive behaviors. mRNA expression of ERalpha in the
      preoptic area and AR in the nucleus taeniae were elevated in male spotted
      antbirds during the nonbreeding season when circulating T concentrations were
      low. This unusual seasonal receptor regulation may represent a means for the year
      round regulation of vertebrate aggressive behavior via steroids by increasing the
      brain's sensitivity to sex steroids during the nonbreeding season.

PMID- 17443773
TI  - Neurite-specific Ca2+ dynamics underlying sound processing in an auditory
      interneurone.
AB  - Concepts on neuronal signal processing and integration at a cellular and
      subcellular level are driven by recording techniques and model systems available.
      The cricket CNS with the omega-1-neurone (ON1) provides a model system for
      auditory pattern recognition and directional processing. Exploiting ON1's planar
      structure we simultaneously imaged free intracellular Ca(2+) at both input and
      output neurites and recorded the membrane potential in vivo during acoustic
      stimulation. In response to a single sound pulse the rate of Ca(2+) rise followed
      the onset spike rate of ON1, while the final Ca(2+) level depended on the mean
      spike rate. Ca(2+) rapidly increased in both dendritic and axonal arborizations
      and only gradually in the axon and the cell body. Ca(2+) levels were particularly
      high at the spike-generating zone. Through the activation of a Ca(2+)-sensitive
      K(+) current this may exhibit a specific control over the cell's electrical
      response properties. In all cellular compartments presentation of species
      specific calling song caused distinct oscillations of the Ca(2+) level in the
      chirp rhythm, but not the faster syllable rhythm. The Ca(2+)-mediated
      hyperpolarization of ON1 suppressed background spike activity between chirps,
      acting as a noise filter. During directional auditory processing, the functional
      interaction of Ca(2+)-mediated inhibition and contralateral synaptic inhibition
      was demonstrated. Upon stimulation with different sound frequencies, the
      dendrites, but not the axonal arborizations, demonstrated a tonotopic response
      profile. This mirrored the dominance of the species-specific carrier frequency
      and resulted in spatial filtering of high frequency auditory inputs.

PMID- 17443774
TI  - Transgene expression of prion protein induces crinophagy in intermediate
      pituitary cells.
AB  - The cellular form of the prion protein (PrP(C)) is a plasma membrane-anchored
      glycoprotein whose physiological function is poorly understood. Here we report
      the effect of transgene expression of Xenopus PrP(C) fused to the C-terminus of
      the green fluorescent protein (GFP-PrP(C)) specifically in the neuroendocrine
      intermediate pituitary melanotrope cells of Xenopus laevis. In the transgenic
      melanotrope cells, the level of the prohormone proopiomelanocortin (POMC) in the
      secretory pathway was reduced when the cells were (i) exposed for a relatively
      long time to the transgene product (by physiologically inducing transgene
      expression), (ii) metabolically stressed, or (iii) forced to produce unfolded
      POMC. Intriguingly, although the overall ultrastructure was normal, electron
      microscopy revealed the induction of lysosomes taking up POMC secretory granules
      (crinophagy) in the transgenic melanotrope cells, likely causing the reduced POMC
      levels. Together, our results indicate that in neuroendocrine cells transgene
      expression of PrP(C) affects the functioning of the secretory pathway and induces
      crinophagy.

PMID- 17443775
TI  - Subunit-dependent cadmium and nickel inhibition of acid-sensing ion channels.
AB  - Acid-sensing ion channels (ASIC) are ligand-gated cation channels that are highly
      expressed in peripheral sensory and central neurons. ASIC are transiently
      activated by decreases in extracellular pH and are thought to play important
      roles in sensory perception, neuronal transmission, and excitability, and in the
      pathology of neurological conditions, such as brain ischemia. We demonstrate here
      that the heavy metals Ni(2+) and Cd(2+) dose-dependently inhibit ASIC currents in
      hippocampus CA1 neurons and in Chinese hamster ovary (CHO) cells heterologously
      expressing these channels. The effects of both Ni(2+) and Cd(2+) were voltage
      independent, fast, and reversible. Neither metal affected activation and
      desensitization kinetics but rather decreased pH-sensitivity. Moreover, distinct
      ASIC isoforms were differentially inhibited by Ni(2+) and Cd(2+). External
      application of 1 mM Ni(2+) rapidly inhibited homomeric ASIC1a and heteromeric
      ASIC1a/2a channels without affecting ASIC1b, 2a, and ASIC3 homomeric channels and
      ASIC1a/3 and 2a/3 heteromeric channels. In contrast, external Cd(+) (1 mM)
      inhibited ASIC2a and ASIC3 homomeric channels and ASIC1a/2a, 1a/3, and 2a/3
      heteromeric channels but not ASIC1a homomeric channels. The acid-sensing current
      in isolated rat hippocampus CA1 neurons, thought to be carried primarily by
      ASIC1a and 1a/2a, was inhibited by 1 mM Ni(2+). The current study identifies ASIC
      as a novel target for the neurotoxic heavy metals Cd(2+) and Ni(2+).

PMID- 17443776
TI  - Survival, synaptogenesis, and regeneration of adult mouse spiral ganglion neurons
      in vitro.
AB  - The inner ear spiral ganglion is populated by bipolar neurons connecting the
      peripheral sensory receptors, the hair cells, with central neurons in auditory
      brain stem nuclei. Hearing impairment is often a consequence of hair cell death,
      e.g., from acoustic trauma. When deprived of their peripheral targets, the spiral
      ganglion neurons (SGNs) progressively degenerate. For effective clinical
      treatment using cochlear prostheses, it is essential to maintain the SGN
      population. To investigate their survival dependence, synaptogenesis, and
      regenerative capacity, adult mouse SGNs were separated from hair cells and
      studied in vitro in the presence of various neurotrophins and growth factors.
      Coadministration of fibroblast growth factor 2 (FGF-2) and glial cell line
      derived neurotrophic factor (GDNF) provided support for long-term survival, while
      FGF-2 alone could strongly promote neurite regeneration. Fibroblast growth factor
      receptor FGFR-3-IIIc was found to upregulate and translocate to the nucleus in
      surviving SGNs. Surviving SGNs formed contacts with other SGNs after they were
      deprived of the signals from the hair cells. In coculture experiments, neurites
      extending from SGNs projected toward hair cells. Interestingly, adult mouse
      spiral ganglion cells could carry out both symmetric and asymmetric cell division
      and give rise to new neurons. The authors propose that a combination of FGF-2 and
      GDNF could be an efficient route for clinical intervention of secondary
      degeneration of SGNs. The authors also demonstrate that the adult mammalian inner
      ear retains progenitor cells, which could commit neurogenesis.

PMID- 17443777
TI  - A quantum of neurotransmitter causes minis in multiple postsynaptic cells at the
      Caenorhabditis elegans neuromuscular junction.
AB  - The polyadic synapse, where a single presynaptic active zone associates with two
      or more postsynaptic cells, exists in both mammals and invertebrates. An
      important but unresolved question is whether synaptic transmission occurs between
      the presynaptic site and its various postsynaptic partners. Using the dual whole
      cell voltage clamp technique, we analyzed miniature postsynaptic currents (mPSCs
      or minis) at the C. elegans neuromuscular junction (NMJ), which is a polyadic
      synapse. We found that neighboring muscle cells at the same position along the
      body axis had high frequencies of concurrent mPSCs, which could not be explained
      by pure chance. Although body-wall muscle cells are electrically coupled, the
      high frequency of concurrent mPSCs was not due to electrical coupling because
      there was no correlation between the frequency of concurrent mPSCs and the degree
      of electrical coupling; the rise time of concurrent mPSCs was identical to that
      of nonconcurrent mPSCs but distinct from that of junctional currents (I(j)); and
      a mutant defective in electrical coupling showed normal frequency of concurrent
      mPSCs. Our analyses suggest that a single quantum of neurotransmitter may cause
      mPSCs in multiple postsynaptic cells at polyadic synapses, and that high-fidelity
      synaptic transmission occurs between the presynaptic site and its various
      postsynaptic partners. Thus, polyadic synapses could be a distinct mechanism for
      synaptic divergence and for synchronizing activities of postsynaptic cells.

PMID- 17443778
TI  - Attention-like processes underlying optomotor performance in a Drosophila choice
      maze.
AB  - The authors present a novel paradigm for studying visual responses in Drosophila.
      An eight-level choice maze was found to reliably segregate fly populations
      according to their responses to moving stripes displayed on a computer screen.
      Visual responsiveness was robust in wild-type flies, and performance depended on
      salience effects such as stimulus color and speed. Analysis of individual fly
      choices in the maze revealed that stereotypy, or choice persistence, contributed
      significantly to a strain's performance. On the basis of these observations, the
      authors bred wild-type flies for divergent visual phenotypes by selecting
      individual flies displaying extreme stereotypy. Selected flies alternated less
      often in the sequential choice maze than unselected flies, showing that
      stereotypy could evolve across generations. The authors found that selection for
      increased stereotypy impaired flies' responsiveness to competing stimuli in tests
      for attention-like behavior in the maze. Visual selective attention was further
      investigated by electrophysiology, and it was found that increased stereotypy
      also impaired responsiveness to competing stimuli at the level of brain activity.
      Combined results present a comprehensive approach to studying visual responses in
      Drosophila, and show that behavioral performance involves attention-like
      processes that are variable among individuals and thus sensitive to artificial
      selection.

PMID- 17443779
TI  - Genetic and pharmacological studies of GluR5 modulation of inhibitory synaptic
      transmission in the anterior cingulate cortex of adult mice.
AB  - In the anterior cingulate cortex (ACC), GluR5-containing kainate receptor
      mediated the small portion of excitatory postsynaptic current. However, little is
      known about its role in modulation of neurotransmitter release in this brain
      region. In the present study, we address this question by using selective GluR5
      agonist and antagonist, as well as GluR5(-/-) mice. Our results showed that
      activation of GluR5 induced action potential-dependent GABA release, which is
      also required for the activation of voltage-dependent calcium channel and Ca(2+)
      influx. The effect of GluR5 activation is selective to the GABAergic, but not
      glutamatergic synaptic transmission. Endogenous activation of GluR5 also enhanced
      GABA release to ACC pyramidal neurons and the corresponding postsynaptic tonic
      GABA current. Our results suggest the somatodendritic, but not presynaptic GluR5,
      in modulation of GABA release. The endogenous GluR5 activation and the subsequent
      tonic GABA current may play an inhibitory role in ACC-related brain functions.

PMID- 17443780
TI  - Electrical stimulation promotes peripheral axon regeneration by enhanced neuronal
      neurotrophin signaling.
AB  - Electrical stimulation of cut peripheral nerves at the time of their surgical
      repair results in an enhancement of axon regeneration. Regeneration of axons
      through nerve allografts was used to evaluate whether this effect is due to an
      augmentation of cell autonomous neurotrophin signaling in the axons or signaling
      from neurotrophins produced in the surrounding environment. In the thy-1-YFP-H
      mouse, a single 1 h application of electrical stimulation at the time of surgical
      repair of the cut common fibular nerve results in a significant increase in the
      proportion of YFP+ dorsal root ganglion neurons, which were immunoreactive for
      BDNF or trkB, as well as an increase in the length of regenerating axons through
      allografts from wild type litter mates, both 1 and 2 weeks later. Axon growth
      through allografts from neurotrophin-4/5 knockout mice or grafts made acellular
      by repeated cycles of freezing and thawing is normally very poor, but electrical
      stimulation results in a growth of axons through these grafts, which is similar
      to that observed through grafts from wild type mice after electrical stimulation.
      When cut nerves in NT-4/5 knockout mice were electrically stimulated, no
      enhancement of axon regeneration was found. Electrical stimulation thus produces
      a potent enhancement of the regeneration of axons in cut peripheral nerves, which
      is independent of neurotrophin production by cells in their surrounding
      environment but is dependent on stimulation of trkB and its ligands in the
      regenerating axons themselves.

PMID- 17443781
TI  - Glutamate regulates neurite outgrowth of cultured descending brain neurons from
      larval lamprey.
AB  - In larval lamprey, descending brain neurons, which regenerate their axons
      following spinal cord injury, were isolated and examined in cell culture to
      identify some of the factors that regulate neurite outgrowth. Focal application
      of 5 mM or 25 mM L-glutamate to single growth cones inhibited outgrowth of the
      treated neurite, but other neurites from the same neuron were not inhibited, an
      effect that has not been well studied for neurons in other systems. Glutamate
      induced inhibition of neurite outgrowth was abolished by 10 mM kynurenic acid.
      Application of high potassium media to growth cones inhibited neurite outgrowth,
      an effect that was blocked by 2 mM cobalt or 100 microM cadmium, suggesting that
      calcium influx via voltage-gated channels contributes to glutamate-induced
      regulation of neurite outgrowth. Application of glutamate to growth cones in the
      presence of 2 microM omega-conotoxin MVIIC (CTX) still inhibited neurite
      outgrowth, while CTX blocked high potassium-induced inhibition of neurite
      outgrowth. Thus, CTX blocked virtually all of the calcium influx resulting from
      depolarization. To our knowledge, this is the first direct demonstration that
      calcium influx via ligand-gated ion channels can contribute to regulation of
      neurite outgrowth. Finally, focal application of glutamate to the cell bodies of
      descending brain neurons inhibited outgrowth of multiple neurites from the same
      neuron, and this is the first demonstration that multiple neurites can be
      regulated in this fashion. Signaling mechanisms involving intracellular calcium,
      similar to those shown here, may be important for regulating axonal regeneration
      following spinal cord injury in the lamprey.

PMID- 17443782
TI  - The serotonin receptor SER-1 (5HT2ce) contributes to the regulation of locomotion
      in Caenorhabditis elegans.
AB  - Serotonin (5-hydroxytryptamine: 5HT) is an important neuroactive substance in the
      model roundworm, Caenorhabditis elegans. Aside from having effects in feeding and
      egg-laying, 5HT inhibits motility and also modulates several locomotory
      behaviors, notably food-induced slowing and foraging. Recent evidence showed that
      a serotonergic 5HT2-like receptor named SER-1 (also known as 5HT2ce) was
      responsible for the effect of 5HT on egg-laying. Here we confirm this observation
      and show that SER-1 also plays an important role in locomotion. A mutant lacking
      SER-1 was found to be highly resistant to exogenous 5HT in the absence of food
      and this resistant phenotype was rescued by reintroducing the SER-1 gene in a
      mutant background. Pharmacological studies showed that the same antagonists that
      blocked the activity of recombinant SER-1 in vitro also inhibited the effect of
      5HT on motility, suggesting the same receptor was responsible for both effects.
      When tested for locomotory behaviors, the SER-1 mutant was found to be moderately
      defective in food-induced slowing. In addition, the mutant changed direction more
      frequently than the wildtype when searching for food, suggesting that SER-1 may
      play a role in navigational control during foraging. Both these effects required
      the presence of MOD-1, a 5HT gated chloride channel, and the results indicate
      that SER-1 and MOD-1 modulate these behaviors through a common pathway. On the
      basis of expression analysis of a ser-1::GFP translational fusion, SER-1 is
      prominently located in central, integrating neurons of the head ganglia (RIA and
      RIC) but not the body wall musculature. The evidence suggests that SER-1 controls
      locomotion through indirect modulation of neuromuscular circuits and has effects
      both on speed and direction of movement.

PMID- 17443783
TI  - HVC microlesions do not destabilize the vocal patterns of adult male zebra
      finches with prior ablation of LMAN.
AB  - The songs of adult male zebra finches (Taeniopygia guttata) arise by an
      integration of activity from two neural pathways that emanate from the
      telencephalic nucleus HVC (proper name). One pathway descends directly from HVC
      to the vocal premotor nucleus RA (the robust nucleus of the arcopallium) whereas
      a second pathway descends from HVC into a basal ganglia circuit (the anterior
      forebrain pathway, AFP) that also terminates in RA. Although HVC neurons that
      project directly to RA outnumber those that contribute to the AFP, both
      populations are distributed throughout HVC. Thus, partial ablation (microlesion)
      of HVC should damage both pathways in a proportional manner. We report here that
      bilateral HVC microlesions in adult male zebra finches produce an immediate loss
      of song stereotypy from which birds recover, in some cases within 3 days. The
      contribution of the AFP to the onset of song destabilization was tested by
      ablating the output nucleus of this circuit (LMAN, the lateral magnocellular
      nucleus of the anterior nidopallium) prior to bilateral HVC microlesions. Song
      stereotypy was largely unaffected. Together, our findings suggest that adult
      vocal production involves nonproportional integration of two streams of neural
      activity with opposing effects on song--HVC's direct projection to RA underlies
      production of stereotyped song whereas the AFP seems to facilitate vocal
      variation. However, the rapid recovery of song in birds with HVC microlesions
      alone suggests the presence of dynamic corrective mechanisms that favor vocal
      stereotypy.

PMID- 17443784
TI  - Nitric oxide modulates sodium taste via a cGMP-independent pathway.
AB  - Insects, like other animals, require sodium chloride (NaCl) as part of their
      normal diet and detect it with contact chemoreceptors on the body surface. By
      adjusting the responsiveness of the chemosensory neurons within these receptors
      insects can modify the intake of salt and other nutrients, and it has been
      hypothesized that the responsiveness of chemosensory neurons is regulated by
      nitric oxide (NO). To identify potential sources of NO in the periphery, the
      authors applied the NO-sensitive fluorescent probe 4,5-diaminofluorescein and the
      universal NO synthase antibody, and found that in locusts NO is synthesized
      within one particular class of cells of the epidermis, the glandular cells, from
      where it may diffuse to neighboring chemosensory neurons. The effects of NO on
      chemosensory neurons were investigated by recording from contact chemoreceptors
      on the leg while perfusing it with drugs that interfere with NO signaling.
      Results showed that both endogenous and exogenous NO decreased the frequency of
      action potentials in chemosensory neurons in response to stimulation with NaCl by
      acting via a cyclic guanosine monophosphate-independent pathway. Variation of the
      NaCl concentration in the perfusion solution demonstrated that the synthesis of
      NO in glandular cells depends on the NaCl concentration in the hemolymph. By
      contrast NO increased the frequency of action potentials in chemosensory neurons
      in response to sucrose stimulation. The authors suggest that NO released from
      glandular cells modulates the responsiveness of chemosensory neurons to regulate
      NaCl intake, and hypothesize that NO may play a key role in the signaling of salt
      and sugars.

PMID- 17443785
TI  - Eph receptor and ephrin signaling in developing and adult brain of the honeybee
      (Apis mellifera).
AB  - Roles for Eph receptor tyrosine kinase and ephrin signaling in vertebrate brain
      development are well established. Their involvement in the modulation of
      mammalian synaptic structure and physiology is also emerging. However, less is
      known of their effects on brain development and their function in adult
      invertebrate nervous systems. Here, we report on the characterization of Eph
      receptor and ephrin orthologs in the honeybee, Apis mellifera (Am), and their
      role in learning and memory. In situ hybridization for mRNA expression showed a
      uniform distribution of expression of both genes across the developing pupal and
      adult brain. However, in situ labeling with Fc fusion proteins indicated that the
      AmEphR and Amephrin proteins were differentially localized to cell body regions
      in the mushroom bodies and the developing neuropiles of the antennal and optic
      lobes. In adults, AmEphR protein was localized to regions of synaptic contacts in
      optic lobes, in the glomeruli of antennal lobes, and in the medial lobe of the
      mushroom body. The latter two regions are involved in olfactory learning and
      memory in the honeybee. Injections of EphR-Fc and ephrin-Fc proteins into the
      brains of adult bees, 1 h before olfactory conditioning of the proboscis
      extension reflex, significantly reduced memory 24 h later. Experimental amnesia
      in the group injected with ephrin-Fc was apparent 1 h post-training. Experimental
      amnesia was also induced by post-training injections with ephrin-Fc suggesting a
      role in recall. This is the first demonstration that Eph molecules function to
      regulate the formation of memory in insects.

PMID- 17443786
TI  - Hypothalamus region-specific global gene expression profiling in early stages of
      central endocrine disruption in rat neonates injected with estradiol benzoate or
      flutamide.
AB  - To identify genes linked to early stages of disruption of brain sexual
      differentiation, hypothalamic region-specific microarray analyses were performed
      using a microdissection technique with neonatal rats exposed to endocrine-acting
      drugs. To validate the methodology, the expression fidelity of microarrays was
      first examined with two-round amplified antisense RNAs (aRNAs) from methacarn
      fixed paraffin-embedded tissue (PET) in comparison with expression in unfixed
      frozen tissue (UFT). Decline of expression fidelity when compared with the 1x
      amplified aRNAs from UFTs was found as a result of the preferential amplification
      of the 3' side of mRNAs in the second round in vitro transcription. However,
      expression patterns for the 2x-amplified aRNAs were mostly identical between
      methacarn-fixed PET and UFT, suggesting no obvious influence of methacarn
      fixation and subsequent paraffin embedding on expression levels. Next, in the
      main experiment, neonatal rats at birth were treated subcutaneously either with
      estradiol benzoate (EB; 10 microg/pup) or flutamide (FA; 250 microg/pup), and
      medial preoptic area (MPOA)-specific microarray analysis was performed 24 h later
      using 2x-amplified aRNAs from methacarn-fixed PET. Numbers of genes showing
      constitutively high expression in the MPOA predominated in males, implying a link
      with male-type growth supported by perinatal testosterone. Around 60% of genes
      showing sex differences in expression demonstrated altered levels after EB
      treatment in females, suggesting an involvement of genes necessary for brain
      sexual differentiation. When compared with EB, FA affected a rather small number
      of genes, but fluctuation was mostly observed in females, as with EB. Moreover,
      many selected genes common to EB and FA showed down-regulation in females with
      both drugs, suggesting a common mechanism for endocrine center disruption in
      females, at least at early stages of post-natal development.

PMID- 17443787
TI  - Neural precursor cells from a fatal human motoneuron disease differentiate
      despite aberrant gene expression.
AB  - Precursor cells of the human central nervous system can be cultured in vitro to
      reveal pathogenesis of diseases or developmental disorders. Here, we have studied
      the biology of neural precursor cells (NPCs) from patients of lethal congenital
      contracture syndrome (LCCS), a severe motoneuron disease leading to prenatal
      death before the 32nd gestational week. LCCS fetuses are immobile because of a
      motoneuron defect, seen as degeneration of the anterior horn and descending
      tracts of the developing spinal cord. The genetic defect for the syndrome is
      unknown. We show that NPCs isolated postmortem from LCCS fetuses grow and are
      maintained in culture, but display increased cell cycle activity. Global
      transcript analysis of undifferentiated LCCS precursor cells present with changes
      in EGF-related signaling when compared with healthy age-matched human controls.
      Further, we show that LCCS-derived NPCs differentiate into cells of neuronal and
      glial lineage and that the initial differentiation is not accompanied by overt
      apoptosis. Cells expressing markers Islet-1 and Hb9 are also generated from the
      LCCS NPCs, suggesting that the pathogenic mechanism of LCCS does not directly
      affect the differentiation capacity or survival of the cells, but the absence of
      motoneurons in LCCS may be caused by a noncell autonomous mechanism.

PMID- 17443788
TI  - Social experience organizes parallel networks in sensory and limbic forebrain.
AB  - Successful social behavior can directly influence an individual's reproductive
      success. Therefore, many organisms readily modify social behavior based on past
      experience. The neural changes induced by social experience, however, remain to
      be fully elucidated. We hypothesize that social modulation of neural systems not
      only occurs at the level of individual nuclei, but also of functional networks,
      and their relationships with behavior. We used the green anole lizard (Anolis
      carolinensis), which displays stereotyped, visually triggered social behaviors
      particularly suitable for comparisons of multiple functional networks in a social
      context, to test whether repeated aggressive interactions modify behavior and
      metabolic activity in limbic-hypothalamic and sensory forebrain regions, assessed
      by quantitative cytochrome oxidase (a slowly accumulating endogenous metabolic
      marker) histochemistry. We found that aggressive interactions potentiate
      aggressive behavior, induce changes in activities of individual nuclei, and
      organize context-specific functional neural networks. Surprisingly, this
      experiential effect is not only present in a limbic-hypothalamic network, but
      also extends to a sensory forebrain network directly relevant to the behavioral
      expression. Our results suggest that social experience modulates organisms'
      social behavior via modifying sensory and limbic neural systems in parallel both
      at the levels of individual regions and networks, potentially biasing perceptual
      as well as limbic processing.

PMID- 17443789
TI  - Glutamate AMPA/kainate receptors, not GABA(A) receptors, mediate estradiol
      induced sex differences in the hypothalamus.
AB  - Sex differences in brain morphology underlie physiological and behavioral
      differences between males and females. During the critical perinatal period for
      sexual differentiation in the rat, gonadal steroids act in a regionally specific
      manner to alter neuronal morphology. Using Golgi-Cox impregnation, we examined
      several parameters of neuronal morphology in postnatal day 2 (PN2) rats. We found
      that in the ventromedial nucleus of the hypothalamus (VMN) and in areas just
      dorsal and just lateral to the VMN that there was a sex difference in total
      dendritic spine number (males greater) that was abolished by treating female
      neonates with exogenous testosterone. Dendritic branching was similarly sexually
      differentiated and hormonally modulated in the VMN and dorsal to the VMN. We then
      used spinophilin, a protein that positively correlates with the amount of
      dendritic spines, to investigate the mechanisms underlying these sex differences.
      Estradiol, which mediates most aspects of masculinization and is the aromatized
      product of testosterone, increased spinophilin levels in female PN2 rats to that
      of males. Muscimol, an agonist at GABA(A) receptors, did not affect spinophilin
      protein levels in either male or female neonates. Kainic acid, an agonist at
      glutamatergic AMPA/kainate receptors, mimicked the effect of estradiol in
      females. Antagonizing AMPA/kainate receptors with NBQX prevented the estradiol
      induced increase in spinophilin in females but did not affect spinophilin level
      in males.

PMID- 17443790
TI  - Overexpression of Bcl-2 or Bcl-xL prevents spiral ganglion neuron death and
      inhibits neurite growth.
AB  - Spiral ganglion neurons (SGNs) provide afferent innervation to the cochlea and
      rely on contact with hair cells (HCs) for their survival. Following
      deafferentation due to hair cell loss, SGNs gradually die. In a rat culture
      model, we explored the ability of prosurvival members of the Bcl-2 family of
      proteins to support the survival and neurite outgrowth of SGNs. We found that
      overexpression of either Bcl-2 or Bcl-xL significantly increases SGN survival in
      the absence of neurotrophic factors, establishing that the Bcl-2 pathway is
      sufficient for SGN cell survival and that SGN deprived of trophic support die by
      an apoptotic mechanism. However, in contrast to observations in central neurons
      and PC12 cells where Bcl-2 appears to promote neurite growth, both Bcl-2 and Bcl
      xL overexpression dramatically inhibit neurite outgrowth in SGNs. This inhibition
      of neurite growth by Bcl-2 occurs in nearly all SGNs even in the presence of
      multiple neurotrophic factors implying that Bcl-2 directly inhibits neurite
      growth rather than simply rescuing a subpopulation of neurons incapable of
      extending neurites without additional stimuli. Thus, although overexpression of
      prosurvival members of the Bcl-2 family prevents SGN loss following trophic
      factor deprivation, the inhibition of neurite growth by these molecules may limit
      their efficacy for support of auditory nerve maintenance or regeneration
      following hair cell loss.

PMID- 17443791
TI  - Costorage of BDNF and neuropeptides within individual dense-core vesicles in
      central and peripheral neurons.
AB  - Some central and peripheral neurons synthesize brain-derived neurotrophic factor
      (BDNF), and, after anterograde transport, release it at synapses. By
      immunocytochemistry, we examined, in rat and mouse, the subcellular localization
      of BDNF and BDNF/peptide coexistence, under normal conditions or after
      intrathecal infusion of nerve growth factor. In dorsal root ganglion neurons and
      afferent terminals, and in the parabrachial projection to amygdala, we show that
      BDNF is costored in individual dense-core vesicles (DCVs) with the neuropeptides
      calcitonin gene-related peptide (CGRP) and substance P. At both locations, nerve
      endings costoring all three peptides were fairly rare. Remarkably however,
      costorage occurred in a stoichiometric ratio of 0.7 BDNF:1 CGRP:1 substance P,
      and DCVs contained 31 (spinal cord) -36 (amygdala) times the amount of BDNF
      detected in agranular vesicles. This is the first direct demonstration in
      peripheral and central neurons from two different mammals, that a growth factor
      is selectively packaged together with neuropeptide transmitters within individual
      DCVs. It provides structural bases for differential release upon stimulation, and
      has important implications for understanding BDNF transmitter function.

PMID- 17443792
TI  - Serotonin in a diencephalic nucleus controlling communication in an electric
      fish: sexual dimorphism and relationship to indicators of dominance.
AB  - Serotonin regulates aggressive behavior. The production or release of serotonin
      is sexually dimorphic and related to social rank in many species. We examined
      serotonin expression in the central posterior/prepacemaker nucleus (CP/PPn) of
      the electric fish Apteronotus leptorhynchus. The CP/PPn is a thalamic nucleus
      that controls agonistic and reproductive electrocommunication signals known as
      chirps and gradual frequency rises. In parts of the CP/PPn that control chirping,
      females had more than twice as many serotonergic fibers and terminals as did
      males. Serotonin immunoreactivity in chirp-controlling areas of the CP/PPn was
      also negatively correlated with two indicators of dominance: electric organ
      discharge (EOD) frequency and body mass. Within sexes, the negative correlation
      between EOD frequency and serotonergic innervation of the PPn was significant in
      females, but not in males. Females with higher EOD frequencies had less serotonin
      in the CP/PPn than did females with lower EOD frequencies. Thus, the CP/PPn
      contained more serotonin in females than in males, and in particular, more
      serotonin in females with EOD frequencies typical of social subordinates than in
      females with EOD frequencies typical of social dominants. These results, combined
      with previous findings that serotonin inhibits chirping and that females chirp
      much less than males, suggest that serotonin may link sex, social rank, and the
      production of agonistic communication signals. The relative simplicity of the
      neural circuits that control the EOD and chirping make the electromotor system
      well-suited for studying the cellular, physiological, and behavioral mechanisms
      by which serotonin modulates agonistic communication.

PMID- 17443793
TI  - Development of sex differences in the principal nucleus of the bed nucleus of the
      stria terminalis of mice: role of Bax-dependent cell death.
AB  - Neuron number in the principal nucleus of the bed nucleus of the stria terminalis
      (BNSTp) is greater in adult male mice than in females. Deletion of the
      proapoptotic gene, Bax, increases the number of BNSTp cells in adulthood and
      eliminates the sex difference in cell number. Here, we map the ontogeny of sex
      differences in nuclear volume and cell number in the BNSTp of neonatal mice, and
      evaluate the role of cell death in the development of these differences. We find
      that BNSTp volume and cell number do not differ between male and female wild-type
      mice on postnatal days P3, P5, or P7. Sex differences emerge after the first
      postnatal week and both measures are significantly greater in males than in
      females on P9 and P11. Cell death, assessed by TUNEL staining, was observed in
      the BNSTp of both sexes from P1-P8. Females had more TUNEL-positive cells than
      males from approximately P3-P6, with the maximum number of dying cells observed
      on P5/P6. To test whether the Bax gene is required for sexually dimorphic cell
      death in the BNSTp, TUNEL cells were counted on P6 in Bax -/- mice and their Bax
      +/+ siblings. Bax gene deletion nearly abolished TUNEL-positive cells in the
      BNSTp of both sexes. Together, these findings support the interpretation that the
      sex difference in BNSTp cell number seen in adulthood is due to Bax-dependent,
      sexually dimorphic cell death during the first week of life.

PMID- 17443794
TI  - Nicotine regulates mRNA expression of feeding peptides in the arcuate nucleus in
      neonatal rat pups.
AB  - Maternal smoking results in low birth weight. Using a neonatal gastric intubation
      model corresponding to the third trimester in humans, nicotine, the major
      psychoactive ingredient in tobacco, causes growth retardation in rat pups. Here,
      we wanted to determine the underlying mechanisms of nicotine's anorexic effects.
      In adults, body weight and energy expenditure are regulated by the adiposity
      hormone leptin and the orexigenic peptides neuropeptide Y (NPY) and agouti
      related peptide (AgRP) and anorexic peptides proopiomelanocortin (POMC) and
      cocaine- and amphetamine-regulated transcript (CART) expressed in the
      hypothalamic arcuate (Arc) nucleus. Activation of nicotinic acetylcholine
      receptors (nAChRs) could regulate leptin release and/or peptide expression in the
      Arc. Neonatal rat pups were treated twice daily with nicotine (0.25, 1.5, and 3
      mg/kg) from postnatal day 1 to 8 (P1-8). This resulted in an upregulation of
      heteromeric nAChR binding sites in the ventromedial nucleus of the hypothalamus
      and Arc. Nicotine at all three doses significantly reduced body weight gain and
      increased mRNA expression of NPY, AgRP, and POMC effects, which were blocked by
      dihydro-beta-erythroidine (DHbetaE), an alpha4beta2* nAChR antagonist, but CART
      expression was unaffected. In contrast, serum leptin levels were significantly
      increased only by 3 and 1.5 mg/kg, and the increase was only partially blocked by
      DHbetaE. These data suggest that in neonates chronic nicotine regulates body
      weight gain independent from serum leptin levels by a central mechanism involving
      alpha4beta2* heteromeric nAChRs and stimulated increased expression of the
      anorexic peptide POMC. Whereas, increased NPY and AgRP expression could be a
      secondary response to reduction in weight gain.

PMID- 17443796
TI  - Exposure to environmental enrichment elicits differential hippocampal cell
      proliferation: role of individual responsiveness to anxiety.
AB  - Environmental enrichment (EE) is a largely employed behavioral procedure in which
      animals are exposed to high stimulation compared with conventional housing
      conditions. Animal exposure to an EE exerts beneficial effects on the performance
      of different learning tasks and induces a number of behavioral, neurochemical,
      and neuroanatomical changes including hippocampal cell proliferation. However,
      the importance of voluntary interaction with the environment in these changes has
      not been clearly resolved yet. Moreover, the effects of a complex environment on
      animal emotionality still remains questionable and has not been explored in
      detail under conditions that allow unmasking individual responses among subjects
      in a group. The present study was aimed at exposing groups of rats to an EE, and
      analyzing individual differences in activity levels during EE sessions. We
      observed differences with respect to the activity level displayed by rats during
      the enriched sessions, which correlated with differences in the rate of
      hippocampal cell proliferation. It is suggested that exposure to EE may reduce
      anxiety-like behaviors and may elicit individual differences on emotional
      reactions positively linked with hippocampal neurogenesis and testosterone
      levels.

PMID- 17443795
TI  - Locomotor activity is regulated by D2-like receptors in Drosophila: an anatomic
      and functional analysis.
AB  - In mammals, dopamine 2-like receptors are expressed in distinct pathways within
      the central nervous system, as well as in peripheral tissues. Selected neuronal
      D2-like receptors play a critical role in modulating locomotor activity and, as
      such, represent an important therapeutic target (e.g. in Parkinson's disease).
      Previous studies have established that proteins required for dopamine (DA)
      neurotransmission are highly conserved between mammals and the fruit fly
      Drosophila melanogaster. These include a fly dopamine 2-like receptor (DD2R;
      Hearn et al. PNAS 2002 99(22):14554) that has structural and pharmacologic
      similarity to the human D2-like (D2R). In the current study, we define the
      spatial expression pattern of DD2R, and functionally characterize flies with
      reduced DD2 receptor levels. We show that DD2R is expressed in the larval and
      adult nervous systems, in cell groups that include the Ap-let cohort of
      peptidergic neurons, as well as in peripheral tissues including the gut and
      Malpighian tubules. To examine DD2R function in vivo, we generated RNA
      interference (RNAi) flies with reduced DD2R expression. Behavioral analysis
      revealed that these flies show significantly decreased locomotor activity,
      similar to the phenotype observed in mammals with reduced D2R expression. The fly
      RNAi phenotype can be rescued by administration of the DD2R synthetic agonist
      bromocriptine, indicating specificity for the RNAi effect. These results suggest
      Drosophila as a useful system for future studies aimed at identifying modifiers
      of dopaminergic signaling/locomotor function.

PMID- 17443797
TI  - Greater hippocampal neuronal recruitment in food-storing than in non-food-storing
      birds.
AB  - Previous research has shown heightened recruitment of new neurons to the
      chickadee hippocampus in the fall. The present study was conducted to determine
      whether heightened fall recruitment is associated with the seasonal onset of food
      storing by comparing neurogenesis in chickadees and a non-food-storing species,
      the house sparrow. Chickadees and house sparrows were captured in the wild in
      fall and spring and received multiple injections of the cell birth marker
      bromodeoxyuridine (BrdU). Birds were held in captivity and the level of
      hippocampal neuron recruitment was assessed after 6 weeks. Chickadees showed
      significantly more hippocampal neuronal recruitment than house sparrows. We found
      no seasonal differences in hippocampal neuronal recruitment in either species. In
      chickadees and in house sparrows, one-third of new cells labeled for BrdU also
      expressed the mature neuronal protein, NeuN. In a region adjacent to the
      hippocampus, the hyperpallium apicale, we observed no significant differences in
      neuronal recruitment between species or between seasons. Hippocampal volume and
      total neuron number both were greater in spring than in fall in chickadees, but
      no seasonal differences were observed in house sparrows. Enhanced neuronal
      recruitment in the hippocampus of food-storing chickadees suggests a degree of
      neurogenic specialization that may be associated with the spatial memory
      requirements of food-storing behavior.

PMID- 17443798
TI  - Circadian changes in Drosophila motor terminals.
AB  - In Drosophila melanogaster, as in most other higher organisms, a circadian clock
      controls the rhythmic distribution of rest/sleep and locomotor activity. Here we
      report that the morphology of Drosophila flight neuromuscular terminals changes
      between day and night, with a rhythm in synaptic bouton size that continues in
      constant darkness, but is abolished during aging. Furthermore, arrhythmic
      mutations in the clock genes timeless and period also disrupt this circadian
      rhythm. Finally, these clock mutants also have an opposing effect on the
      nonrhythmic phenotype of neuronal branching, with tim mutants showing a dramatic
      hyperbranching morphology and per mutants having fewer branches than wild-type
      flies. These unexpected results reveal further circadian as well as nonclock
      related pleiotropic effects for these classic behavioral mutants.

PMID- 17443799
TI  - Splice-isoform specific immunolocalization of neuronal nitric oxide synthase in
      mouse and rat brain reveals that the PDZ-complex-building nNOSalpha beta-finger
      is largely exposed to antibodies.
AB  - Knock out mice deficient for the splice-isoform alphaalpha of neuronal nitric
      oxide synthase (nNOSalphaalpha) display residual nitric oxide synthase activity
      and immunosignal. To attribute this signal to the two minor neuronal nitric oxide
      synthase splice variants, betabeta and gammagamma, we generated isoform-specific
      anti-peptide antibodies against the nNOSalphaalpha specific betabeta-finger motif
      involved in PDZ domain scaffolding and the nNOSbetabeta specific N-terminus. The
      nNOSalphaalpha betabeta-finger-specific antibody clearly recognized the 160-kDa
      band of recombinant nNOSalphaalpha on Western blots. Using immunocytochemistry,
      this antibody displayed, in rats and wild-type mice, a labeling pattern similar
      to but not identical with that obtained using a commercial pan-nNOS antibody.
      This similarity indicates that the majority of immunocytochemically detectable
      nNOS is not likely to be complexed with PDZ-domain proteins via the betabeta
      finger motif. This conclusion was confirmed by the inhibition of PSD-95/nNOS
      interaction by the nNOSalphaalpha betabeta-finger antibody in pull-down assays.
      By contrast, nNOSalphaalpha betabeta-finger labeling was clearly reduced in
      hippocampal and cortical neuropil areas enriched in NMDA receptor complex
      containing spine synapses. In nNOSalphaalpha knock out mice, nNOSalphaalpha was
      not detectable, whereas the pan-nNOS antibody showed a distinct labeling of cell
      bodies throughout the brain, most likely reflecting betabeta/gammagamma-isoforms
      in these cells. The nNOSbetabeta antibody clearly detected bacterial expressed
      nNOSbetabeta fusion protein and nNOSbetabeta in overexpressing HEK cells by
      Western blotting. Immunocytochemically, individual cell bodies in striatum,
      cerebral cortex, and in some brain stem nuclei were labeled in knock out but not
      in wild-type mice, indicating an upregulation of nNOSbetabeta in nNOSalphaalpha
      deficient animals.

PMID- 17443800
TI  - Targeting HSP70 to motoneurons protects locomotor activity from hyperthermia in
      Drosophila.
AB  - Heat shock preconditioning can enhance locomotor and synaptic performance during
      subsequent hyperthermia. The molecular basis underlying this neural phenotypic
      modification is largely unknown. Here we report that directing the expression of
      the 70 kDa heat shock protein (HSP70) to motoneurons protected larval locomotor
      activity of Drosophila. Tissue-specific expression showed that motoneurons were
      critical for developing HSP70-mediated thermoprotection of locomotor activity,
      whereas peripheral sensory neurons, dopaminergic neurons, serotonergic neurons,
      and muscle cells alone were insufficient. Targeting HSP70 to motoneurons caused
      structural plasticity of axonal terminals associated with increased transmitter
      release at neuromuscular junctions at high temperature. The thermoprotection
      induced by motoneuronal expression of HSP70 mimicked the protective effect of a
      prior heat shock (36 degrees C, 1 h; 25 degrees C, 1 h) but the effects of heat
      shock and motoneuronal expression of HSP70 were not additive. In the absence of
      heat shock pretreatment, ubiquitously expressed transgenic HSP70 activated the
      transcription of endogenous hsp70 genes. These results demonstrate that
      motoneurons were critical for HSP70-mediated thermoprotection, and that
      transgenic HSP70 activated the transcription of endogenous hsp70 in motoneurons
      with the result that a mix of transgenic and endogenous HSP70 conferred
      thermoprotection in Drosophila larva.

PMID- 17443801
TI  - Gaseous neuromodulator-related genes expressed in the brain of honeybee Apis
      mellifera.
AB  - Nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO) are thought
      to act as gaseous neuromodulators in the brain across species. For example, in
      the brain of honeybee Apis mellifera, NO plays important roles in olfactory
      learning and discrimination, but the existence of H2S- and CO-mediated signaling
      pathways remains unknown. In the present study, we identified the genes of nitric
      oxide synthase (NOS), soluble guanylyl cyclase (sGC), cystathionine beta-synthase
      (CBS), and heme oxygenase (HO) from the honeybee brain. The honeybee brain
      contains at least one gene for each of NOS, CBS, and HO. The deduced proteins for
      NOS, CBS, and HO are thought to contain domains to generate NO, H2S, and CO,
      respectively, and to contain putative Ca2+/calmodulin-binding domains. On the
      other hand, the honeybee brain contains three subunits of sGC: sGCalpha1,
      sGCbeta1, and sGCbeta3. Phylogenetic analysis of sGC revealed that Apis sGCalpha1
      and sGCbeta1 are closely related to NO- and CO-sensitive sGC subunits, whereas
      Apis sGCbeta3 is closely related to insect O2-sensitive sGC subunits. In
      addition, we performed in situ hybridization for Apis NOS mRNA and NADPH
      diaphorase histochemistry in the honeybee brain. The NOS gene was strongly
      expressed in the optic lobes and in the Kenyon cells of the mushroom bodies. NOS
      activity was detected in the optic lobes, the mushroom bodies, the central body
      complex, the lateral protocerebral lobes, and the antennal lobes. These findings
      suggest that NO is involved in various brain functions and that H2S and CO can be
      endogenously produced in the honeybee brain.

PMID- 17443802
TI  - Sexually dimorphic SCAMP1 expression in the forebrain motor pathway for song
      production of juvenile zebra finches.
AB  - Mechanisms regulating sexual differentiation of the zebra finch song system are
      not well understood. The present study was designed to more fully characterize
      secretory carrier membrane protein 1 (SCAMP1), which was identified in a cDNA
      microarray screen as showing increased expression in the forebrains of developing
      male compared with female zebra finches. We completed the sequence of the open
      reading frame and used in situ hybridization to compare mRNA in song control
      regions of juvenile (25-day-old) individuals. Expression was significantly
      greater in the HVC (used as a proper name) and robust nucleus of the arcopallium
      (RA) in males than in females. Immunohistochemistry revealed that SCAMP1 protein
      is also expressed in these two brain regions, and qualitatively appears greater
      in males. Western analysis confirmed that the protein is increased in the
      telencephalon of males when compared with females at 25 days of age. These
      results are consistent with the idea that SCAMP1 is involved in masculinization
      of these brain areas, perhaps facilitating the survival of cells within them.

PMID- 17443803
TI  - Prestin-prestin and prestin-GLUT5 interactions in HEK293T cells.
AB  - The remarkable hearing sensitivity and frequency selectivity in mammals is
      attributed to cochlear amplifier in the outer hair cells (OHCs). Prestin, a
      membrane protein in the lateral wall of OHC plasma membrane, is required for OHC
      electromotility and cochlear amplifier. In addition, GLUT5, a fructose
      transporter, is reported to be abundant in the plasma membrane of the OHC lateral
      wall and has been originally proposed as the OHC motor protein. Here we provide
      evidence of interactions between prestin/prestin and prestin/GLUT5 in transiently
      transfected HEK293T cells. We used a combination of techniques: (1) membrane
      colocalization by confocal microscopy, (2) fluorescence resonance energy transfer
      (FRET) by fluorescence activated cell sorting (FACS), (3) FRET by acceptor
      photobleaching, (4) FRET by fluorescence lifetime imaging (FRET-FLIM), and (5)
      coimmunoprecipitation. Our results suggest that homomeric and heteromeric prestin
      interactions occur in native OHCs to facilitate its electromotile function and
      that GLUT5 interacts with prestin for its elusive function.

PMID- 17443804
TI  - Time-dependent postsynaptic AMPA GluR1 receptor recruitment in the cingulate
      synaptic potentiation.
AB  - The anterior cingulate cortex (ACC) is critical for brain functions including
      learning, memory, fear and pain. Long-term synaptic potentiation (LTP), a
      cellular model for learning and memory, has been reported in the ACC neurons.
      Unlike LTP in the hippocampus and amygdala, two key structures for memory and
      fear, little is known about the synaptic mechanism for the expression of LTP in
      the ACC. Here we use whole-cell patch clamp recordings to demonstrate that
      cingulate LTP requires the functional recruitment of GluR1 AMPA receptors; and
      such events are rapid and completed within 5-10 min after LTP induction. Our
      results demonstrate that the GluR1 subunit is essential for synaptic plasticity
      in the ACC and may play critical roles under physiological and pathological
      conditions.

PMID- 17443805
TI  - Effects of progesterone and its reduced metabolites, dihydroprogesterone and
      tetrahydroprogesterone, on the expression and phosphorylation of glycogen
      synthase kinase-3 and the microtubule-associated protein tau in the rat
      cerebellum.
AB  - Progesterone exerts a variety of actions in the brain, where it is rapidly
      metabolized to 5alpha-dihydroprogesterone (DHP) and 3alpha,5alpha
      tetrahydroprogesterone (THP). The effect of progesterone and its metabolites on
      the expression and phosphorylation of the microtubule-associated protein Tau and
      glycogen synthase kinase 3beta (GSK3beta), a kinase involved in Tau
      phosphorylation, were assessed in two progesterone-sensitive brain areas: the
      hypothalamus and the cerebellum. Administration of progesterone, DHP, and THP to
      ovariectomized rats did not affect Tau and GSK3beta assessed in whole
      hypothalamic homogenates. In contrast, progesterone and its metabolites resulted
      in a significant decrease in the expression of Tau and GSK3beta in the
      cerebellum. Furthermore, progesterone administration resulted in an increase in
      the phosphorylation of two epitopes of Tau (Tau-1 and PHF-1) phosphorylated by
      GSK3beta, but did not affect the phosphorylation of an epitope of Tau (Ser262)
      that is GSK3beta insensitive. These effects were accompanied by a decrease in the
      phosphorylation of GSK3beta in serine, which is associated to an increase in its
      activity, suggesting that the effect of progesterone on Tau-1 and PHF-1
      phosphorylation in the cerebellum is mediated by GSK3beta. The regulation of Tau
      expression and phosphorylation by progesterone may contribute to the hormonal
      regulation of cerebellar function by the modification of neuronal cytoskeleton.

PMID- 17443806
TI  - Synaptic transmission is impaired at neuronal autonomic synapses in agrin-null
      mice.
AB  - Neuronal synapse formation is a multistep process regulated by several pre- and
      postsynaptic adhesion and signaling proteins. Recently, we found that agrin acts
      as one such synaptogenic factor at neuronal synapses in the PNS by demonstrating
      that structural synapse formation is impaired in the superior cervical ganglia
      (SCG) of z+ agrin-deficient mice and in SCG cultures derived from those animals.
      Here, we tested whether synaptic function is defective in agrin-null (AGD-/-)
      ganglia and began to define agrin's mechanism of action. Our electrophysiological
      recordings of compound action potentials showed that presynaptic stimulation
      evoked action potentials in approximately 40% of AGD-/- ganglionic neurons
      compared to 90% of wild-type neurons; moreover, transmission could not be
      potentiated as in wild-type or z+ agrin-deficient ganglia. Intracellular
      recordings also showed that nerve-evoked excitatory postsynaptic potentials in
      AGD-/- neurons were only 1/3 the size of those in wild-type neurons and mostly
      subthreshold. Consistent with these defects in transmission, we found an
      approximately 40-50% decrease in synapse number in AGD-/- ganglia and cultures,
      and decreased levels of differentiation at the residual synapses in culture.
      Furthermore, surface levels of acetylcholine receptors (AChRs) were equivalent in
      cultured AGD-/- and wild-type neurons, and depolarization reduced the synaptic
      localization of AChRs in AGD-/- but not wild-type neurons. These findings provide
      the first direct demonstration that agrin is required for proper structural and
      functional development of an interneuronal synapse in vivo. Moreover, they
      suggest a novel role for agrin, in stabilizing the postsynaptic density of nAChR
      at nascent neuronal synapses.

PMID- 17443807
TI  - Sex differences in and hormonal regulation of Kv1 potassium channel gene
      expression in the electric organ: molecular control of a social signal.
AB  - Electric fish communicate with electric organ (EO) discharges (EODs) that are
      sexually dimorphic, hormone-sensitive, and often individually distinct. The cells
      of the EO (electrocytes) of the weakly electric fish Sternopygus possess delayed
      rectifying K+ currents that systematically vary in their activation and
      deactivation kinetics, and this precise variation in K+ current kinetics helps
      shape sex and individual differences in the EOD. Because members of the Kv1
      subfamily produce delayed rectifier currents, we cloned a number of genes in the
      Kv1 subfamily from the EO of Sternopygus. Using our sequences and those from
      genome databases, we found that in teleost fish Kv1.1 and Kv1.2 exist as
      duplicate pairs (Kv1.1a&b, Kv1.2a&b) whereas Kv1.3 does not. Using real-time
      quantitative RT-PCR, we found that Kv1.1a and Kv1.2a, but not Kv1.2b, expression
      in the EO is higher in high EOD frequency females (which have fast EO K+
      currents) than in low EOD frequency males (which have slow EO K+ currents).
      Systemic treatment with dihydrotestosterone decreased Kv1.1a and Kv1.2a, but not
      Kv1.2b, expression in the EO, whereas treatment with human chorionic gonadotropin
      (hCG) increased Kv1.2a but not Kv1.1a or Kv1.2b expression in the EO. Thus,
      systematic variation in the ratios of Kv1 channels expressed in the EO is
      correlated with individual differences in and sexual dimorphism of a
      communication signal.

PMID- 17443808
TI  - A screen for neurotransmitter transporters expressed in the visual system of
      Drosophila melanogaster identifies three novel genes.
AB  - The fly eye provides an attractive substrate for genetic studies, and critical
      transport activities for synaptic transmission and pigment biogenesis in the
      insect visual system remain unknown. We therefore screened for transporters in
      Drosophila melanogaster that are down-regulated by genetically ablating the eye.
      Using a large panel of transporter specific probes on Northern blots, we
      identified three transcripts that are down-regulated in flies lacking eye tissue.
      Two of these, CG13794 and CG13795, are part of a previously unknown subfamily of
      putative solute carriers within the neurotransmitter transporter family. The
      third, CG4476, is a member of a related subfamily that includes characterized
      nutrient transporters expressed in the insect gut. Using imprecise excision of a
      nearby transposable P element, we have generated a series of deletions in the
      CG4476 gene. In fast phototaxis assays, CG4476 mutants show a decreased
      behavioral response to light, and the most severe mutant behaves as if it were
      blind. These data suggest an unforeseen role for the "nutrient amino acid
      transporter" subfamily in the nervous system, and suggest new models to study
      transport function using the fly eye.

PMID- 17443809
TI  - Activity-dependent formation and functions of chondroitin sulfate-rich
      extracellular matrix of perineuronal nets.
AB  - Extracellular matrix molecules--including chondroitin sulfate proteoglycans,
      hyaluronan, and tenascin-R--are enriched in perineuronal nets (PNs) associated
      with subsets of neurons in the brain and spinal cord. In the present study, we
      show that similar cell type-dependent extracellular matrix aggregates are formed
      in dissociated cell cultures prepared from early postnatal mouse hippocampus.
      Starting from the 5th day in culture, accumulations of lattice-like extracellular
      structures labeled with Wisteria floribunda agglutinin were detected at the cell
      surface of parvalbumin-expressing interneurons, which developed after 2-3 weeks
      into conspicuous PNs localized around synaptic contacts at somata and proximal
      dendrites, as well as around axon initial segments. Physiological recording and
      intracellular labeling of PN-expressing neurons revealed that these are large
      fast-spiking interneurons with morphological characteristics of basket cells. To
      study mechanisms of activity-dependent formation of PNs, we performed
      pharmacological analysis and found that blockade of action potentials,
      transmitter release, Ca2+ permeable AMPA subtype of glutamate receptors or L-type
      Ca2+ voltage-gated channels strongly decreased the extracellular accumulation of
      PN components in cultured neurons. Thus, we suggest that Ca2+ influx via AMPA
      receptors and L-type channels is necessary for activity-dependent formation of
      PNs. To study functions of chondroitin sulfate-rich PNs, we treated cultures with
      chondroitinase ABC that resulted in a prominent reduction of several major PN
      components. Removal of PNs did not affect the number and distribution of
      perisomatic GABAergic contacts but increased the excitability of interneurons in
      cultures, implicating the extracellular matrix of PNs in regulation of
      interneuronal activity.

PMID- 17443810
TI  - Differential contribution of extracellular and intracellular calcium sources to
      basal transmission and long-term potentiation in the sympathetic ganglion of the
      rat.
AB  - Calcium involved in basal ganglionic transmission and long-term potentiation
      (LTP) can arise either by influx from the extracellular medium or release from
      intracellular stores. No attempts have yet been made to concurrently explore the
      contributions of extracellular and intracellular Ca2+ to basal ganglionic
      transmission or LTP. Here, we investigate this subject using the superior
      cervical ganglion of the rat. To explore the extracellular Ca2+ contribution, we
      evaluated basal transmission and LTP at different extracellular Ca2+
      concentrations. To assess intracellular Ca2+ release, we explored the
      contribution of the calcium-induced calcium release process by overactivation or
      blockade of ryanodine-sensitive Ca2+ receptor channel with caffeine, and also by
      blocking either IP3R with Xestospongin C or the sarco(endo)plasmic reticulum Ca2+
      ATPase pump with thapsigargin. Extracellular Ca2+ affected ganglionic basal
      transmission and LTP to different extents. While 25% of the physiological Ca2+
      concentration supported 80% of basal transmission, 50% of normal Ca2+ was
      required to achieve 80% of LTP. Notably, disruption of intracellular Ca2+ release
      by all the drugs tested apparently did not affect basal ganglionic transmission
      but impaired LTP. We conclude that basal transmission requires only a small level
      of Ca2+ entry, while LTP expression not only requires more Ca2+ entry but is also
      dependent on Ca2+ release from intracellular stores.

PMID- 17443811
TI  - Retinal ganglion cell protection by 17-beta-estradiol in a mouse model of
      inherited glaucoma.
AB  - Glaucoma is the second leading cause of blindness in the world. The ultimate
      cause of vision loss due to glaucoma is thought to be retinal ganglion cell (RGC)
      apoptosis. Neuroprotection of RGC is becoming an important approach of glaucoma
      therapy. Several lines of evidence suggest that estrogen has neurotrophic and
      neuroprotective properties. In this study, we examine the role of estrogen in
      preventing RGC loss in DBA/2J mouse, an in vivo model of an inherited
      (pigmentary) glaucoma. Two-month-old female DBA/2J mice were anesthetized and
      ovariectomized with or without subcutaneous 17beta-estradiol (betaE2) pellet
      implantation. RGC survival was evaluated from flat-mounted whole retinas by
      counting retrograde-labeled cells. The loss of nerve fibers and RGC were also
      evaluated in paraffin-fixed retinal cross sections. Biochemical alterations in
      the retinas of DBA/2J mice in response to systemic injection of betaE2 were also
      examined. We have made several important observations showing that: (1) betaE2
      treatment reduced the loss of RGC and neurofibers through inhibition of ganglion
      cell apoptosis, (2) betaE2 activated Akt and cAMP-responsive-element-binding
      protein (CREB), (3) betaE2 up-regulated thioredoxin-1 (Trx-1) expression, (4)
      betaE2 reduced the increased activations of mitogen-activated protein kinases
      (MAPK) and NF-kappaB, (5) betaE2 inhibited the increased interleukin-18 (IL-18)
      expression, and (6) treatment with tamoxifen, an estrogen receptor antagonist,
      blocked betaE2-mediated activation of Akt and inhibition of MAPK phosphorylation
      in the retinas of DBA/2J mice. These findings suggest the possible involvement of
      multiple biochemical events, including estrogen receptor/Akt/CREB/thioredoxin-1,
      and estrogen receptor/MAPK/NF-kappaB, in estrogen-mediated retinal ganglion cell
      protection.

PMID- 17443812
TI  - Exposure to neonatal separation stress alters exploratory behavior and
      corticotropin releasing factor expression in neurons in the amygdala and
      hippocampus.
AB  - Evidence is accumulating that early emotional experience interferes with the
      development of the limbic system, which is involved in perception and regulation
      of emotional behaviors as well as in learning and memory formation. Limbic brain
      regions, as well as hypothalamic regions and other, nonlimbic areas contain
      specific neuron subpopulations, which express and release corticotropin releasing
      factor (CRF). Since these neurons serve to connect limbic function to endocrine,
      stress-related responses, we proposed that stressful experience during early
      postnatal brain development should interfere with the development of CRF
      containing neurons, particularly in brain regions essential for emotional
      regulation. Applying neonatal separation stress (daily 1 h separation from the
      parents and litter mates) as stressor, the number of immunocytochemically
      identified CRF-expressing neurons/fibers was quantified in the amygdala,
      hippocampus, paraventricular nucleus of the hypothalamus, piriform cortex, and
      the somatosensory cortex of 3-week-old stressed and nonstressed Octodon degus, a
      semi-precocial rodent. Compared to controls neonatally stressed animals showed
      significantly lower levels of CRF-positive fibers (-60%) in the central amygdala,
      significantly less CRF-positive neurons in the dentate gyrus (-28%) and the CA1
      region (-29%) and significantly lower CRF cell densities in the somatosensory
      cortex (-26%). On the other hand, we found significantly higher numbers of CRF
      immunoreactive neurons in the basolateral amygdaloid complex (+192%) of stressed
      animals compared to nonstressed controls. No differences in CRF-immunoreactive
      cell densities were detected in the other regions. Additional behavioral analysis
      revealed significantly elevated exploratory behavior (+34%) in stressed animals
      compared to controls, which might indicate reduced anxiety in the stressed
      animals.

PMID- 17443813
TI  - Effect of incubation temperature and androgens on dopaminergic activity in the
      leopard gecko, Eublepharis macularius.
AB  - Male leopard geckos that hatch from eggs incubated at a female-biased temperature
      (Tf) behave differently when compared with males hatching at a temperature which
      produces a male-biased sex ratio (Tm). We investigated the effect of incubation
      temperature and androgen implantation on aspects of the dopaminergic system of Tf
      and Tm males. Our data suggest that more dopamine (DA) is stored in the nucleus
      accumbens of naive Tf males compared with naive Tm males when they encounter a
      receptive female conspecific across a barrier. No difference was measured in the
      preoptic area and the ventral tegmental area (VTA). This difference in
      intracellular DA levels in a motivation-related brain nucleus might be correlated
      with differences in sociosexual behavior observed between the two morphs. There
      were no differences in tyrosine hydroxylase (TH) expressing cell numbers in the
      VTA of cholesterol (CH)-implanted naive castrated Tf and Tm males. Only Tf males
      implanted with testosterone had significantly higher TH immunopositive cell
      numbers in the VTA compared with CH- and dihydrotestosterone-implanted Tf males.
      These data indicate that both the embryonic environment as well as the
      circulating hormonal milieu can modulate neurochemistry, which might in turn be a
      basis for individual variation in behavior.

PMID- 17443814
TI  - Regeneration in zebrafish lateral line neuromasts: expression of the neural
      progenitor cell marker sox2 and proliferation-dependent and-independent
      mechanisms of hair cell renewal.
AB  - Mechanosensory hair cells are essential for audition in vertebrates, and in many
      species, have the capacity for regeneration when damaged. Regeneration is robust
      in the fish lateral line system as new hair cells can reappear after damage
      induced by waterborne aminoglycoside antibiotics, platinum-based drugs, and heavy
      metals. Here, we characterize the loss and reappearance of lateral line hair
      cells induced in zebrafish larvae treated with copper sulfate using diverse
      molecular markers. Transgenic fish that express green fluorescent protein in
      different cell types in the lateral line system have allowed us to follow the
      regeneration of hair cells after different damage protocols. We show that
      conditions that damage only differentiated hair cells lead to reappearance of new
      hair cells within 24 h from nondividing precursors, whereas harsher conditions
      are followed by a longer recovery period that is accompanied by extensive cell
      division. In order to characterize the cell population that gives rise to new
      hair cells, we describe the expression of a neural stem cell marker in
      neuromasts. The zebrafish sox2 gene is strongly expressed in neuromast progenitor
      cells, including those of the migrating lateral line primordium, the accessory
      cells that underlie the hair cells in neuromasts, and in interneuromastic cells
      that give rise to new neuromasts. Moreover, we find that most of the cells that
      proliferate within the neuromast during regeneration express this marker. Thus,
      our results describe the dynamics of hair cell regeneration in zebrafish and
      suggest the existence of at least two mechanisms for recovery of these cells in
      neuromasts.

PMID- 17443815
TI  - Pak1 regulates dendritic branching and spine formation.
AB  - The serine/threonine kinase p21-activated kinase 1 (Pak1) modulates actin and
      microtubule dynamics. The neuronal functions of Pak1, despite its abundant
      expression in the brain, have not yet been fully delineated. Previously, we
      reported that Pak1 mediates initiation of dendrite formation. In the present
      study, the role of Pak1 in dendritogenesis, spine formation and maintenance was
      examined in detail. Overexpression of constitutively active-Pak1 in immature
      cortical neurons increased not only the number of the primary branching on apical
      dendrites but also the number of basal dendrites. In contrast, introduction of
      dominant negative-Pak caused a reduction in both of these morphological features.
      The length and the number of secondary apical branch points of dendrites were not
      significantly different in cultured neurons expressing these mutant forms,
      suggesting that Pak1 plays a role in dendritogenesis. Pak1 also plays a role in
      the formation and maintenance of spines, as evidenced by the altered spine
      morphology, resulting from overexpression of mutant forms of Pak1 in immature and
      mature hippocampal neurons. Thus, our results provide further evidence of the key
      role of Pak1 in the regulation of dendritogenesis, dendritic arborization, the
      spine formation, and maintenance.

PMID- 17443816
TI  - BAX contributes to Doppel-induced apoptosis of prion-protein-deficient Purkinje
      cells.
AB  - Research efforts to deduce the function of the prion protein (PrPc) in knock-out
      mouse mutants have revealed that large deletions in the PrPc genome result in the
      ectopic neuronal expression of the prion-like protein Doppel (Dpl). In our
      analysis of one such line of mutant mice, Ngsk Prnp0/0 (NP0/0), we demonstrate
      that the ectopic expression of Dpl in brain neurons induces significant levels of
      cerebellar Purkinje cell (PC) death as early as six months after birth. To
      investigate the involvement of the mitochondrial proapoptotic factor BAX in the
      Dpl-induced apoptosis of PCs, we have analyzed the progression of PC death in
      aging NP0/0:Bax-/- double knockout mutants. Quantitative analysis of cell numbers
      showed that significantly more PCs survived in NP0/0:Bax-/- double mutants than
      in the NP0/0:Bax+/+ mutants. However, PC numbers were not restored to wildtype
      levels or to the increased number of PCs observed in Bax-/- mutants. The partial
      rescue of NP0/0 PCs suggests that the ectopic expression of Dpl induces both BAX
      dependent and BAX-independent pathways of cell death. The activation of glial
      cells that is shown to be associated topographically with Dpl-induced PC death in
      the NP0/0:Bax+/+ mutants is abolished by the loss of Bax expression in the double
      mutant mice, suggesting that chronic inflammation is an indirect consequence of
      Dpl-induced PC death.

PMID- 17443817
TI  - Neuronal recruitment in adult zebra finch brain during a reproductive cycle.
AB  - Previous studies suggest that adult neurogenesis and neuronal replacement are
      related to the acquisition of new information. The present study supports this
      hypothesis by showing that there is an increase in new neuron recruitment in
      brains of adult male and female zebra finches that coincides with the need to
      memorize vocalizations of nestlings before they fledge. We counted [(3)H]
      Thymidine labeled neurons 40 days after [(3)H]-Thymidine injections. These counts
      were made in the parents' brains at the time eggs hatched, at the time juveniles
      fledged and still needed parental care, and at the time juveniles were already
      independent. We focused on nidopallium caudale (NC), a brain region which plays a
      role in sound processing. Recruitment of new NC neurons increased at the time the
      young fledged, followed by a significant decrease when the young reached
      independence. We suggest that this increase enables parents to recognize their
      own young when they are still dependent on parental feeding, yet easily lost
      among other fledglings in the colony. We saw no such increase in neuronal
      recruitment in the olfactory bulb, suggesting anatomical specificity for the
      effect seen in NC. We also found a preliminary, positive correlation between
      number of fledglings and number of new NC neurons in the parents' brain at
      fledging, suggesting that the number of neurons recruited is sensitive to the
      number of young fledged.

PMID- 17443818
TI  - Differential effects of stress and amphetamine administration on Fos-like protein
      expression in corticotropin releasing factor-neurons of the rat brain.
AB  - Corticotropin releasing factor (CRF) appears to be critical for the control of
      important aspects of the behavioral and physiological response to stressors and
      drugs of abuse. However, the extent to which the different brain CRF neuronal
      populations are similarly activated after stress and drug administration is not
      known. We then studied, using double immunohistochemistry for CRF and Fos
      protein, stress and amphetamine-induced activation of CRF neurons in cortex,
      central amygdala (CeA), medial parvocellular dorsal, and submagnocellular
      parvocellular regions of the paraventricular nucleus of the hypothalamus (PVNmpd
      and PVNsm, respectively) and Barrington nucleus (Bar). Neither exposure to a
      novel environment (hole-board, HB) nor immobilization (IMO) increased Fos-like
      immunoreactivity (FLI) in the CeA, but they did to the same extent in cortical
      regions. In other regions only IMO increased FLI. HB and IMO both failed to
      activate CRF+ neurons in cortical areas, but after IMO, some neurons expressing
      FLI in the PVNsm and most of them in the PVNmpd and Bar were CRF+. Amphetamine
      administration increased FLI in cortical areas and CeA (with some CRF+ neurons
      expressing FLI), whereas the number of CRF+ neurons increased only in the PVNsm,
      in contrast to the effects of IMO. The present results indicate that stress and
      amphetamine elicited a distinct pattern of brain Fos-like protein expression and
      differentially activated some of the brain CRF neuronal populations, despite
      similar levels of overall FLI in the case of IMO and amphetamine.

PMID- 17443819
TI  - Mutagenesis studies in transgenic Xenopus intermediate pituitary cells reveal
      structural elements necessary for correct prion protein biosynthesis.
AB  - The cellular prion protein (PrP(C)) is generally accepted to be involved in the
      development of prion diseases, but its physiological role is still under debate.
      To obtain more insight into PrP(C) functioning, we here used stable Xenopus
      transgenesis in combination with the proopiomelanocortin (POMC) gene promoter to
      express mutated forms of Xenopus PrP(C) fused to the C-terminus of the green
      fluorescent protein (GFP) specifically in the neuroendocrine Xenopus intermediate
      pituitary melanotrope cells. Similar to GFP-PrP(C), the newly synthesized GFP
      PrP(C)K81A mutant protein was stepwise mono- and di-N-glycosylated to 48- and 51
      kDa forms, respectively, and eventually complex glycosylated to yield a 55-kDa
      mature form. Unlike GFP-PrP(C), the mature GFP-PrP(C)K81A mutant protein was not
      cleaved, demonstrating the endoproteolytic processing of Xenopus PrP(C) at lysine
      residue 81. Surprisingly, removal of the glycosylphosphatidylinositol (GPI)
      anchor signal sequence or insertion of an octarepeat still allowed N-linked
      glycosylation, but the GFP-PrP(C)DeltaGPI and GFP-PrP(C)octa mutant proteins were
      not complex glycosylated and not cleaved, indicating that the GPI/octa mutants
      did not reach the mid-Golgi compartment of the secretory pathway. The transgene
      expression of the mutant proteins did not affect the ultrastructure of the
      melanotrope cells nor POMC biosynthesis and processing, or POMC-derived peptide
      secretion. Together, our findings reveal the evolutionary conservation of the
      site of metabolic cleavage and the importance of the presence of the GPI anchor
      and the absence of the octarepeat in Xenopus PrP(C) for its correct biosynthesis.

PMID- 17443820
TI  - A role for eukaryotic translation initiation factor 2B (eIF2B) in taste memory
      consolidation and in thermal control establishment during the critical period for
      sensory development.
AB  - All species exhibit critical periods for sensory development, yet very little is
      known about the molecules involved in the changes in the network wiring that
      underlies this process. Here the role of transcription regulation of the
      translation machinery was determined by evaluating the expression of
      eIF2Bepsilon, an essential component of translation initiation, in both taste
      preference development and thermal control establishment in chicks. Analysis of
      the expression pattern of this gene after passive-avoidance training revealed
      clear induction of eIF2Bepsilon in both the mesopallium intermediomediale (IMM)
      and in the striatum mediale (StM). In addition, a correlation was found between
      the concentration of methylanthranilate (MeA), which was the malaise substrate in
      the passive-avoidance training procedure, the duration of memory, and the
      expression level of eIF2Bepsilon. Training chicks on a low concentration of MeA
      induced short-term memory and low expression level of eIF2Bepsilon, whereas a
      high concentration of MeA induced long-term memory and a high expression level of
      eIF2Bepsilon in both the IMM and StM. Furthermore, eIF2Bepsilon-antisense "knock
      down" not only reduced the amount of eIF2Bepsilon but also attenuated taste
      memory formation. In order to determine whether induction of eIF2Bepsilon is a
      general feature of neuronal plasticity, we checked whether it was induced in
      other forms of neuronal plasticity, with particular attention to its role in
      temperature control establishment, which represents hypothalamic-related
      plasticity. It was established that eIF2Bepsilon-mRNA was induced in the
      preopotic anterior hypothalamus during heat conditioning. Taken together, these
      results correlate eIF2Bepsilon with sensory development.

PMID- 17443821
TI  - Learning with half a brain.
AB  - Since the 1970s, human subjects that have undergone corpus callosotomy have
      provided important insights into neural mechanisms of perception, memory, and
      cognition. The ability to test the function of each hemisphere independently of
      the other offers unique advantages for investigating systems that are thought to
      underlie cognition. However, such approaches have been limited to mammals. Here
      we describe comparable experiments on an insect brain to demonstrate learning
      associated changes within one brain hemisphere. After training one half of their
      bisected brains, cockroaches learn to extend the antenna supplying that brain
      hemisphere towards an illuminated diode after this has been paired with an odor
      stimulus. The antenna supplying the naive hemisphere shows no response.
      Cockroaches retain this ability for up to 24 h, during which, shortly after
      training, the mushroom body of the trained hemisphere alone undergoes specific
      post-translational alterations of microglomerular synaptic complexes in its
      calyces.

PMID- 17443822
TI  - 5-HT2 receptors in Drosophila are expressed in the brain and modulate aspects of
      circadian behaviors.
AB  - Dysregulation of 5-HT(2) receptor function has been strongly implicated in many
      neuropsychiatric disorders, including schizophrenia. At present, the molecular
      mechanisms linking 5-HT(2) receptor activation to behaviors is not well
      understood. In efforts to elucidate these processes, the fruit fly, Drosophila
      melanogaster, is proposed to serve as a powerful genetically tractable model
      organism to study 5-HT(2) receptor function. Data are presented here on the
      expression of the fly ortholog of the mammalian 5-HT(2) receptor, 5-HT(2)Dro, in
      the larval and adult brain of the fly, and on the involvement of these circuits
      in certain circadian behaviors. In the adult brain, 5-HT(2)Dro is expressed in
      the protocerebrum and ellipsoid body, areas believed to participate in higher
      order behaviors including learning, locomotion, and sensory perception. In the
      third instar larva, 5-HT(2)Dro receptor expression is detected in a specific
      pattern that markedly changes from early to late third instar. To probe the
      function of this receptor we have examined the effects of the 5-HT(2) receptor
      specific agonist DOI in wild type and 5-HT(2)Dro hypomorphic flies on circadian
      behaviors. DOI was found to increase early day activity, eliminate anticipatory
      behavior, and reduce viability. The effects of DOI were significantly diminished
      in a 5-HT(2)Dro hypomorphic strain. Identifying the 5-HT(2)Dro receptor circuitry
      and behaviors they mediate are significant steps towards developing this model
      system to study conserved molecular mechanisms underlying behaviors mediated by 5
      HT(2) receptors in mammalian systems.

PMID- 17443823
TI  - Direct peptide profiling of lateral cell groups of the antennal lobes of Manduca
      sexta reveals specific composition and changes in neuropeptide expression during
      development.
AB  - The paired antennal lobes are the first integration centers for odor information
      in the insect brain. In the sphinx moth Manduca sexta, like in other
      holometabolous insects, they are formed during metamorphosis. To further
      understand mechanisms involved in the formation of this particularly well
      investigated brain area, we performed a direct peptide profiling of a well
      defined cell group (the lateral cell group) of the antennal lobe throughout
      development by MALDI-TOF mass spectrometry. Although the majority of the about
      100 obtained ion signals represent still unknown substances, this first
      peptidomic characterization of this cell group indicated the occurrence of 12
      structurally known neuropeptides. Among these peptides are helicostatin 1,
      cydiastatins 2, 3, and 4, M. sexta-allatotropin (Mas-AT), M. sexta-FLRFamide (Mas
      FLRFamide) I, II, and III, nonblocked Mas-FLRFamide I, and M. sexta-myoinhibitory
      peptides (Mas-MIPs) III, V, and VI. The identity of two of the allatostatins
      (cydiastatins 3 and 4) and Mas-AT were confirmed by tandem mass spectrometry
      (MALDI-TOF/TOF). During development of the antennal lobe, number and frequency of
      ion signals including those representing known peptides generally increased at
      the onset of glomeruli formation at pupal Stage P7/8, with cydiastatin 2,
      helicostatin 1, and Mas-MIP V being the exceptions. Cydiastatin 2 showed
      transient occurrence mainly during the period of glomerulus formation,
      helicostatin 1 was restricted to late pupae and adults, while Mas-MIP V occurred
      exclusively in adult antennal lobes. The power of the applied direct mass
      spectrometric profiling lies in the possibility of chemically identifying
      neuropeptides of a given cell population in a fast and reliable manner, at any
      developmental stage in single specimens. The identification of neuropeptides in
      the antennal lobes now allows to specifically address the function of these
      signaling molecules during the formation of the antennal lobe network.

PMID- 17443824
TI  - Age-related changes in climbing behavior and neural circuit physiology in
      Drosophila.
AB  - Identifying the cellular and molecular basis for functional decline remains key
      to understanding aging. To this end, we have characterized age-dependent changes
      in climbing and the electrophysiology of the giant fiber circuitry in wild type
      (Wt) and mutant flies with altered lifespan (methuselah and fragile-X). Our data
      demonstrate a gradual decline in climbing in Wt and methuselah flies aged 5-45
      days. In contrast, fragile-X flies climbed poorly even at 5 days and failed
      completely at 45 days. We then examined whether synaptic transmission to indirect
      flight muscles along the giant fiber circuit was altered with aging. At 5 days,
      the dorsal longitudinal muscle (DLM) in Wt flies followed high frequency
      stimulation well (at 130 Hz or above). At 35 and 45 days, these flies only
      followed 60-80 Hz. Methuselah flies did not follow stimuli as well as the Wt
      flies did at 5 and 25 days, but they were similar to Wt flies at older ages.
      Fragile-X flies responded poorly even at 5 days (40 Hz) and worsened at 35 days
      (30 Hz). Unlike DLMs, the tergotrochanteral muscle followed high frequency
      stimuli relatively well in all genotypes, suggesting that the peripheral
      interneuron along the DLM pathway or the DLM muscular synapse is prone to age
      dependent functional decline. These studies reveal subcellular structures as
      potential targets of aging, indicating that the giant fiber pathway can be used
      as a model circuit for quantitative studies of aging in flies as well as fly
      models of age-related human neurological disorders.

PMID- 17443825
TI  - Neurotransmitter-induced changes in the intracellular calcium concentration
      suggest a differential central modulation of CCAP neuron subsets in Drosophila.
AB  - The complete sequencing of the Drosophila melanogaster genome allowed major
      progress in the research on invertebrate neuropeptide signaling. However, it is
      still largely unknown how the insect CNS exerts synaptic control over the
      secretory activity of peptidergic neurons; afferent pathways and employed
      chemical transmitters remain largely unidentified. In the present study, we set
      out to identify neurotransmitters mediating synaptic input onto CCAP-expressing
      neurons (N(CCAP)), which play an important role in the regulation of ecdysis
      related events. By in vitro and in situ calcium imaging with synthetic and
      genetically encoded calcium indicators, we provide evidence that differential
      neurotransmitter inputs control the activity of N(CCAP) subsets. In short-term
      culture, almost all N(CCAP) showed increases of the free intracellular calcium
      concentration after application of acetylcholine (ACh) and nicotine, whereas only
      some N(CCAP) responded to glutamate and GABA. In the intact ventral ganglia of
      both larvae and adults, only few N(CCAP) showed intracellular calcium-rises or
      calcium-oscillations after application of cholinergic agonists indicating a
      prevailing central inhibition of most N(CCAP) during these developmental stages.
      In larvae, responding N(CCAP) were primarily located in the third thoracic
      neuromere. At least one N(CCAP) pair in this neuromere belonged to a
      morphologically distinct subset with neurohemal endings on the body wall muscles.
      Our results suggest that N(CCAP) express functional receptors for ACh, glutamate,
      and GABA, and indicate that these transmitters are involved in a context
      dependent regulation of functionally distinct N(CCAP) subsets.

PMID- 17443826
TI  - Recruitment of FoxP2-expressing neurons to area X varies during song development.
AB  - In adult songbirds, neural progenitors proliferate along the lateral ventricles.
      After migration, many of the subsequently formed neuroblasts integrate into the
      song nuclei HVC and Area X that participate in auditory-guided vocal motor
      learning and singing. Recruitment of postembryonically generated neurons into
      HVC, rodent hippocampus, and olfactory bulb has been linked to learning and
      memory. The cellular identity and the role of postembryonically generated neurons
      in Area X are unknown. Here we describe that the majority of new neurons in
      postembryonic Area X of male zebra finches expressed DARPP32 but not choline
      acetyltransferase or parvalbumin. This suggests that they are spiny neurons.
      Retrogradely labeled neurons projecting to thalamic nucleus DLM were not renewed.
      The spiny neurons in Area X were recently shown to express FoxP2, a transcription
      factor critical for normal speech and language development in humans. Since
      increased FoxP2 mRNA expression was previously observed during periods of vocal
      plasticity we investigated whether this increase might be associated with
      neuronal recruitment. Consistent with their spiny phenotype, new neurons in Area
      X did express FoxP2 and recruitment increased transiently during the juvenile
      song learning period. Moreover we found that FoxP2 was expressed in the
      ventricular zone of adult songbirds but was absent from the germinal zones in
      adult mouse brains, the hippocampus, and the subventricular zone. Together these
      results raise the possibility that neuronal recruitment and FoxP2 expression in
      Area X are associated with vocal learning.

PMID- 17443827
TI  - Cell cycle inhibition and retinoblastoma protein overexpression prevent Purkinje
      cell death in organotypic slice cultures.
AB  - Purkinje cells are vulnerable to a number of physical, chemical, and genetic
      insults during development and maturity. Normal development of these cells
      depends on the cell-cell interactions between granule and astroglial cell
      populations. Apoptotic death in Purkinje neurons had been shown to be associated
      with cell cycle activation, and new DNA synthesis is associated with Purkinje
      cell death in staggerer and lurcher mutant mice. Here using an in vitro
      organotypic slice culture model from 9 (P9) and 4 days (P4) old postnatal rats we
      show that the cyclin dependent kinase (cdk) inhibitors (roscovitine, olomoucine,
      and flavopiridol) protect the Purkinje cells from cell death. The results are
      more pronounced in the cerebellar sections from P4 rats. Analysis of Purkinje
      neurons in sections from P4 rats after 1 week of culturing showed that while
      there were very limited calbindin positive neurons in the untreated sections the
      cdk inhibitor treated sections had a notably higher number. Although treatment
      with cdk inhibitors inhibited Purkinje cell loss significantly, the morphology of
      these neurons was abnormal, with stunted dendrites and axons. Since the
      retinoblastoma protein (Rb) is the major pocket protein involved in determining
      the differentiated state of neurons we examined the effect of over-expressing Rb
      in the organotypic cultures. Rb overexpression significantly inhibited the
      Purkinje cell death and these neurons maintained their normal morphology. Thus
      our studies show that the cell death in Purkinje neurons observed in organotypic
      cultures is cell cycle dependent and the optimal survival requires Rb.

PMID- 17443828
TI  - Hormonal and environmental control of song control region growth and new neuron
      addition in adult male house finches, Carpodacus mexicanus.
AB  - In songbirds, testosterone (T) mediates seasonal changes in the sizes and
      neuroanatomical characteristics of brain regions that control singing (song
      control regions; SCRs). One model explaining the mechanisms of the growth of one
      SCR, the HVC, postulates that in the spring increasing photoperiod and
      circulating T concentrations enhance new neuron survival, thus increasing total
      neuron number. However, most research investigating the effects of T on new
      neuron survival has been done in autumn. The present study investigated the
      effects of photoperiod and T treatment on SCR growth and new neuron survival in
      the HVC in photosensitive adult male House Finches, Carpodacus mexicanus, under
      simulated spring-like conditions. Birds were castrated, given T-filled or empty
      Silastic capsules and maintained on short days (SD; 8L:16D) or long days (LD;
      16L:8D). To mark new cells, birds received bromodeoxyuridine injections 11 days
      after experimental manipulations began and were sacrificed 28 days later.
      Testosterone treatment increased the sizes of two SCRs, the HVC and Robust
      nucleus of the arcopallium (RA). Exposure to LD did not affect HVC volume, but
      did increase RA volume. Testosterone treatment increased the total number of HVC
      neurons, but did not affect the number of new HVC neurons. Thus, T initiates SCR
      growth and increases neuron survival, but effects of T on new neuron
      incorporation may be limited in photosensitive birds under spring-like
      conditions. These results provide new insight into the effects of photoperiod and
      T treatment on vernal SCR growth and new neuron incorporation and support current
      models explaining this growth.

PMID- 17443829
TI  - Efficient fluorescence enhancement and cooperative binding of an organic dye in a
      supra-biomolecular host-protein assembly.

PMID- 17443830
TI  - Controlling the sense of enantioselection on surfaces by conformational changes
      of adsorbed modifiers.

PMID- 17443832
TI  - The ball-shaped heteropolytungstates [[Sn(CH3)2(H2O)]24[Sn(CH3)2]12(A
      XW9O34)12]36- (X=P, As): stability, redox and electrocatalytic properties in
      aqueous media.
AB  - The electrochemical behavior of the ball-shaped heteropolytungstates
      [[Sn(CH(3))(2)(H(2)O)](24)[Sn(CH(3))(2)](12)(A-XW(9)O(34))(12)](36-) (X=P, 1; As,
      2) was examined in aqueous electrolytes by redissolution of their respective
      mixed cesium-sodium salts
      Cs(14)Na(22)[[Sn(CH(3))(2)(H(2)O)](24)[Sn(CH(3))(2)](12) (A-PW(9)O(34))(12)]149
      H(2)O (Cs(14)-1) and Cs(14)Na(22)[[Sn(CH(3))(2)(H(2)O)](24)[Sn(CH(3))(2)](12)(A
      AsW(9)O(34))(12)]149 H(2)O (Cs(14)-2). In the studied media, Cs(14)-2 is readily
      soluble in contrast to the significantly less soluble Cs(14)-1. The solubility of
      Cs(14)-1 is increased by the presence of Li(+) ions in solution. Gel filtration
      studies with 1 and 2 rule out a decay of the dodecameric spherical assemblies to
      Keggin-based monomers on the timescale of the experiment. By UV/Vis spectroscopy
      and cyclic voltammetry, 2 was found to be significantly less stable than 1 and
      both polyanions also show rather different decomposition pathways. Polyanion 1
      collapses first into Keggin-type monomers which might contain the trilacunary [A
      alpha-PW(9)O(34)](9-). The final monomeric species obtained from 1 appears to be
      very similar to [PW(11)O(39)](7-), which is the final transformation product of
      [A-alpha-PW(9)O(34)](9-) in the same media. In contrast, 2 does not seem to
      follow an analogous transformation pathway as that of the trilacunary [A-alpha
      AsW(9)O(34)](9-). Importantly, stabilization of 1 is observed in chloride media.
      The fairly long-term stability of 1 in 1 M LiCl, pH 3, has allowed for its
      electrochemical study to be carried out. The solid-state cyclic voltammogram of 1
      entrapped in a carbon paste electrode shows the same characteristics as 1
      dissolved in chloride solutions, thus supporting the conclusion that the
      polyanion is stable in these environments. Controlled potential coulometry on 1
      indicates that the number of electrons consumed in the first wave is larger than
      twenty. To our knowledge, 1 constitutes the first example of a molecule that can
      take up such a large number of electrons resulting in a chemically reversible W
      wave. These properties show promise for future fundamental and applied studies.
      Polyanion 1 is also efficient in the electrocatalytic reduction of NO(x),
      including nitrate. Finally, a remarkable interaction was found between 1 and NO,
      a highly promising feature for biomimetic applications.

PMID- 17443831
TI  - Alpha-substituted phosphonate analogues of lysophosphatidic acid (LPA)
      selectively inhibit production and action of LPA.
AB  - Isoform-selective agonists and antagonists of the lysophosphatidic acid (LPA) G
      protein-coupled receptors (GPCRs) have important potential applications in cell
      biology and therapy. LPA GPCRs regulate cancer cell proliferation, invasion,
      angiogenesis, and biochemical resistance to chemotherapy- and radiotherapy
      induced apoptosis. LPA and its analogues are also feedback inhibitors of the
      enzyme lysophospholipase D (lysoPLD, also known as autotaxin), a central
      regulator of invasion and metastasis. For cancer therapy, the ideal therapeutic
      profile would be a metabolically stabilized pan-LPA receptor antagonist that also
      inhibits lysoPLD. Herein we describe the synthesis of a series of novel alpha
      substituted methylene phosphonate analogues of LPA. Each of these analogues
      contains a hydrolysis-resistant phosphonate mimic of the labile monophosphate of
      natural LPA. The pharmacological properties of these phosphono-LPA analogues were
      characterized in terms of LPA receptor subtype-specific agonist and antagonist
      activity using Ca(2+) mobilization assays in RH7777 and CHO cells expressing the
      individual LPA GPCRs. In particular, the methylene phosphonate LPA analogue is a
      selective LPA(2) agonist, whereas the corresponding alpha-hydroxymethylene
      phosphonate is a selective LPA(3) agonist. Most importantly, the alpha
      bromomethylene and alpha-chloromethylene phosphonates show pan-LPA receptor
      subtype antagonist activity. The alpha-bromomethylene phosphonates are the first
      reported antagonists for the LPA(4) GPCR. Each of the alpha-substituted methylene
      phosphonates inhibits lysoPLD, with the unsubstituted methylene phosphonate
      showing the most potent inhibition. Finally, unlike many LPA analogues, none of
      these compounds activate the intracellular LPA receptor PPARgamma.

PMID- 17443833
TI  - On the interactions of alkyl 2-hydroxycarboxylic acids with alkoxysilanes:
      selective esterification of simple 2-hydroxycarboxylic acids.
AB  - The interactions of a range of monocarboxylic acids with tetramethoxysilane
      Si(OMe)(4) (TMOS), in methanol (MeOH), have been investigated by using (1)H,
      (13)C and (29)Si solution-phase NMR spectroscopy and electrospray mass
      spectrometry (ESMS). Si(OMe)(4) acts as a catalyst/reagent in the selective
      methylation of 2-hydroxycarboxylic acids (2HOAs) in MeOH at room temperature:
      glycolic acid, lactic acid and 2-hydroxybutyric acid are esterified more than a
      hundred times faster in MeOH and Si(OMe)(4) than in MeOH alone. No acceleration
      of methylation is observed for carboxylic acids lacking the 2-hydroxy group.
      Methylation of the 2HOAs is associated with the condensation of individual
      siloxane units to form oligomers. A mechanism is proposed in which 2HOAs attach
      to silicon via the alkoxy group, then subsequently via the carboxyl group in an
      intramolecular rearrangement to form an unstable and reactive cyclic
      intermediate. This intermediate may lead to accelerated methylation of the
      carboxylic acid via nucleophilic attack of MeOH at the carbonyl group, while a
      separate reaction pathway leads to condensation of silanols and/or alkoxysilanes
      leading to oligosiloxanes. The mechanism has implications for the use of 2HOAs as
      templates in sol-gel silica preparation.

PMID- 17443834
TI  - Role of the oriented attachment mechanism in the phase transformation of oxide
      nanocrystals.
AB  - "Bottom-up" methods to obtain nanocrystals usually result in metastable phases,
      even in processes carried out at room temperature or under soft annealing
      conditions. However, stable phases, often associated with anisotropic shapes, are
      obtained in only a few special cases. In this paper we report on the synthesis of
      two well-studied oxides-titanium and zirconium oxide-in the nanometric range, by
      a novel route based on the decomposition of peroxide complexes of the two metals
      under hydrothermal soft conditions, obtaining metastable and stable phases in
      both cases through transformation. High-resolution transmission electron
      microscopy analysis reveals the existence of typical defects relating to growth
      by the oriented attachment mechanism in the stable crystals. The results suggest
      that the mechanism is associated to the phase transformation of these structures.

PMID- 17443835
TI  - Continuous tuning of cadmium sulfide and zinc sulfide nanoparticle size in a
      water-in-supercritical carbon dioxide microemulsion.
AB  - The size and size dispersion of cadmium sulfide and zinc sulfide semiconductor
      nanoparticles can be continuously tuned over a wide range of values by adjusting
      the density of the fluid phase in water-in-supercritical CO2 microemulsions. The
      average size of the ZnS nanoparticles decreases linearly from approximately 9.1
      to 1.9 nm with increasing fluid density from 0.86 to 0.99 g cm(-3) at a water-to
      surfactant ratio (W value) of 10. At a W value of 6, the particle size can be
      tuned from 7.0 to 1.5 nm in the same density range. In the case of CdS
      nanocrystals, the size varied from 7.1 to 2.0 nm when the W value was 10 and from
      4.0 to 1.3 nm when the W value employed was 6, in the same density range.
      Monodispersive CdS and ZnS nanoparticles were synthesized by chemical reaction of
      cadmium or zinc nitrate with sodium sulfide, using two water-in-supercritical CO2
      microemulsions as nanoreactors followed by protection with a fluorinated-thiol
      stabilizer. The stabilizer is introduced at 6 and 16 minutes after the mixing of
      the two microemulsions where the intensity of the characteristic absorption peak
      due to the quantum confinement properties of the CdS and ZnS nanoparticles (280
      and 360 nm) reaches a maximum, respectively. The supercritical CO2 microemulsion
      method represents a simple approach to use a density-tunable solvent for
      synthesizing size-controlled semiconductor nanoparticles over a broad range of
      values.

PMID- 17443836
TI  - Comparison of HPLC and CE methods for the determination of cetirizine
      dihydrochloride in human plasma samples.
AB  - Two methods, capillary electrophoresis (CE) and high-performance liquid
      chromatography (HPLC), for analysis of cetirizine dihydrochloride in small sample
      volumes of human plasma were compared. The CE and HPLC assays were developed and
      validated by analyzing a series of plasma samples containing cetirizine
      dihydrochloride in different concentrations using these two methods. The
      extraction procedure is simple and no complicated purification steps or
      derivatization are required. The analysis time in the HPLC method was shorter
      than that in the CE method, but solvent consumption was considerably lower in the
      CE method. The calibration curve was linear to at least 10-1000 ng/mL both for CE
      and HPLC with r(2) = 0.9993 and r(2) = 0.9994, respectively. The detection limits
      for cetirizine dihydrochloride were 3 and 5 ng/mL with CE and HPLC (a UV detector
      was applied in the both cases), respectively. Both methods were selective, robust
      and specific, allowing reliable quantification of cetirizine dihydrochloride, and
      could be useful for clinical and biomedical investigations.

PMID- 17443837
TI  - Solvent effects on one-bond B-Li coupling constants in boryllithium compounds.
AB  - EOM-CCSD 11B-7Li coupling constants and B chemical shifts have been computed for
      Li-diazaborole and its complexes with one H2O or FLi molecule. B-Li coupling
      constants for a model compound H(2)BLi and its complexes with up to 4 H2O or FLi
      molecules have also been obtained in an attempt to resolve discrepancies between
      the computed values of these properties for isolated Li-diazaborole and
      experimentally determined values for boryllithium in a THF solution. The presence
      of solvent molecules increases the ion-pair character of the B-Li bond, with the
      result that 1J(B-Li) decreases systematically as the basicity and the number of
      solvent molecules increases. In the presence of even a single solvent molecule,
      the boron chemical shift for Li-diazaborole increases, and approaches the
      experimental value. The computed results emphasize the role of the solvent in
      determining these NMR properties.

PMID- 17443838
TI  - ESR imaging investigations of two-phase systems.
AB  - The possibilities of electron spin resonance (ESR) and electron spin resonance
      imaging (ESRI) for investigating the properties of the spin probes TEMPO and
      TEMPOL in two-phase systems have been examined in the systems water/n-octanol,
      Miglyol/Miglyol, and Precirol/Miglyol. Phases and regions of the phase boundary
      could be mapped successfully by means of the isotropic hyperfine coupling
      constants, and, moreover, the quantification of rotational and lateral diffusion
      of the spin probes was possible. For the quantitative treatment of the
      micropolarity, a simplified empirical model was established on the basis of the
      Nernst distribution and the experimentally determined isotropic hyperfine
      coupling constants. The model does not only describe the summarized
      micropolarities of coexisting phases, but also the region of the phase boundary,
      where solvent molecules of different polarities and tendencies to form hydrogen
      bonds compete to interact with the NO group of the spin probe.

PMID- 17443839
TI  - Structural determination of seven new triterpenoids from Kadsura heteroclita by
      NMR techniques.
AB  - Seven new triterpenoids, namely heteroclitalactones G-M (1-7), were isolated from
      the ethanol extract of the stems of Kadsura heteroclita. Structures of these
      compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses.

PMID- 17443840
TI  - Structural determination of a new 2(3 --> 20)abeotaxane with an unusual 13beta
      substitution pattern and a new 6/8/6-ring taxane from Taxus cuspidata.
AB  - A new 2(3 --> 20)abeotaxane with an unusual 13beta-substitution pattern and a new
      6/8/6-ring taxane were isolated from the methanol extract of the needles of Taxus
      cuspidata. The structures were established as 2alpha,7beta-diacetoxy
      5alpha,10beta,13beta-trihydroxy-2(3 --> 20)abeotaxa-4(20), 11-dien-9-one (1) and
      2alpha,5alpha,7beta,9alpha,13alpha-pentahydroxy-10beta-acetoxytaxa-4(20),11-diene
      (2) on the basis of 1D and 2D NMR spectral data and high-resolution FAB-MS
      analyses.

PMID- 17443841
TI  - The evaluation of two-step multivariate adaptive regression splines for
      chromatographic retention prediction of peptides.
AB  - Both the multivariate adaptive regression splines (MARS) and the two-step MARS
      (TMARS) methodologies were applied in a quantitative structure-retention
      relationship (QSRR) context. For seven RPLC systems, QSRR models were built that
      describe the retention times of a set of peptides using a large set of molecular
      descriptors as potential predictor variables. The use of QSRR models for
      chromatographic retention prediction of peptides may be valuable in proteomic
      research to improve the number of correct peptide identifications. Always, 70% of
      the samples was used to derive the QSRR models (calibration set), whereas the
      remaining 30% of the peptides were treated as an independent external test set.
      For four systems, the models obtained by TMARS have better predictive abilities
      than the MARS models. The MARS and TMARS model performance was compared with
      those of other multivariate modelling techniques. For five out of seven systems
      it was observed that the uninformative variable elimination by the partial least
      squares (PLS) approach outperforms all other methods studied. For three systems
      predictive errors smaller than 30 s were obtained. PLS regression and a multiple
      linear regression model based on three descriptors led to the best predictivities
      for the remaining two systems.

PMID- 17443842
TI  - A proteomic study of the major allergens from yellow jacket venoms.
AB  - The venoms of stinging insects belong to the most dangerous allergen sources and
      can cause fatal anaphylactic reactions. Reliable prediction of a patient's risk
      to anaphylactic reactions is vital, and diagnosis requires the knowledge of the
      relevant allergens. Recently, a new hyaluronidase -like glycoprotein from Vespula
      vulgaris (Ves v 2b) was identified. This led us to investigate hyaluronidases and
      also other major allergens from V. germanica and four additional Vespula species.
      By MALDI-Q-TOF-MS, the new hyaluronidase-like protein was shown to be the major
      component of the 43-kDa band in all Vespula species studied. LC-ESI-Q-TOF-MS/MS
      sequencing of Ves g 2a and Ves g 2b facilitated the cloning of their cDNA. Ves v
      2b and Ves g 2b turned out to be essentially identical on protein level. Whereas
      the less abundant "a" form displayed enzymatic activity, the new "b" homologue
      did not. This is probably caused by amino acid exchanges in the active site, and
      it raises questions about the physiological role of this protein. Sequence
      comparisons by MS/MS of antigen 5 and phospholipases from V. vulgaris, germanica,
      maculifrons, pensylvanica, flavopilosa and squamosa revealed the latter as a
      taxonomic outlier and led to the discovery of several not previously reported
      amino acid differences.

PMID- 17443843
TI  - The phosphorylation pattern of bovine heart complex I subunits.
AB  - The phosphoproteome of bovine heart complex I of the respiratory chain has been
      analysed with a procedure based on nondenaturing gel electrophoretic separation
      of complex I from small quantities of mitochondria samples, in-gel digestion, in
      combination with phosphopeptide enrichment by titanium dioxide and MS. The
      results, complemented by analyses of purified samples of complex I, showed
      phosphorylation of five subunits of the complex, 42 kDa (human gene NDUFA10),
      ESSS, B14.5a (human gene NDUFA7), B14.5b (human gene NDUFC2) and B16.6 (GRIM-19).
      MS also revealed the presence of phosphorylated programmed cell death protein
      8(AIF) in native and purified samples of complex I analysed. The possible
      physiological relevance of these findings is discussed.

PMID- 17443844
TI  - Proteomic analysis of pancreatic endocrine tumor cell lines treated with the
      histone deacetylase inhibitor trichostatin A.
AB  - Effects of the histone-deacetylases inhibitor trichostatin A (TSA) on the growth
      of three different human pancreatic endocrine carcinoma cell lines (CM, BON, and
      QGP-1) have been assessed via dosage-dependent growth inhibition curves. TSA
      determined strong inhibition of cell growth with similar IC(50) values for the
      different cell lines: 80.5 nM (CM), 61.6 nM (BON), and 86 nM (QGP-1), by
      arresting the cell cycle in G2/M phase and inducing apoptosis. 2DE and nano-RP
      HPLC-ESI-MS/MS analysis revealed 34, 33, and 38 unique proteins differentially
      expressed after TSA treatment in the CM, BON, and QGP-1 cell lines, respectively.
      The most important groups of modulated proteins belong to cell proliferation,
      cell cycle, and apoptosis classes (such as peroxiredoxins 1 and 2, the diablo
      protein, and HSP27). Other proteins pertain to processes such as regulation of
      gene expression (nucleophosmin, oncoprotein dek), signal transduction (calcium
      calmodulin), chromatin, and cytoskeleton organization (calgizzarin, dynein, and
      lamin), RNA splicing (nucleolin, HNRPC), and protein folding (HSP70). The present
      data are in agreement with previous proteomic analyses performed on pancreatic
      ductal carcinoma cell lines (Cecconi, D. et al.., Electrophoresis 2003; Cecconi,
      D. et al., J. Proteome Res. 2005) and place histone-deacetylases inhibitors among
      the potentially most powerful drugs for the treatment of pancreatic tumors.

PMID- 17443845
TI  - Prevalidation of potential protein biomarkers in toxicology using iTRAQ reagent
      technology.
AB  - Today, toxicoproteomics still relies mainly on 2-DE followed by MS for detection
      and identification of proteins, which might characterize a certain state of
      disease, indicate toxicity or even predict carcinogenicity. We utilized the
      classical 2-DE/MS approach for the evaluation of early protein biomarkers which
      are predictive for chemically induced hepatocarcinogenesis in rats. We were able
      to identify statistically significantly deregulated proteins in N
      nitrosomorpholine exposed rat liver tissue. Based on literature data, biological
      relevance in the early molecular process of hepatocarcinogenicity could be
      suggested for most of these potential biomarkers. However, in order to ensure
      reliable results and to create the prerequisites necessary for integration in
      routine toxicology studies in the future, these protein expression patterns need
      to be prevalidated using independent technology platforms. In the current study,
      we evaluated the usefulness of iTRAQ reagent technology (Applied Biosystems,
      Framingham, USA), a recently introduced MS-based protein quantitation method, for
      verification of the 2-DE/MS biomarkers. In summary, the regulation of 26 2-DE/MS
      derived protein biomarkers could be verified. Proteins like HSP 90-beta, annexin
      A5, ketohexokinase, N-hydroxyarylamine sulfotransferase, ornithine
      aminotransferase, and adenosine kinase showed highly comparable fold changes
      using both proteomic quantitation strategies. In addition, iTRAQ analysis
      delivered further potential biomarkers with biological relevance to the processes
      of hepatocarcinogenicity: e.g. placental form of glutathione S-transferase (GST
      P), carbonic anhydrase, and aflatoxin B1 aldehyde reductase. Our results show
      both the usefulness of iTRAQ reagent technology for biomarker prevalidation as
      well as for identification of further potential marker proteins, which are
      indicative for liver hepatocarcinogenicity.

PMID- 17443846
TI  - Comprehensive analysis of exported proteins from Mycobacterium tuberculosis
      H37Rv.
AB  - Proteins secreted by Mycobacterium tuberculosis play an essential role in the
      pathogenesis of tuberculosis. The culture filtrates of M. tuberculosis H37Rv made
      by Sadamu Nagai (Japan), are considerably enriched for secreted proteins compared
      to other culture filtrates. Complementary approaches were used to identify the
      secreted proteins in these culture filtrates: (i) 2-DE combined with MALDI-TOF MS
      and (ii) LC coupled MS/MS. Peptides derived from a total of 257 proteins were
      identified of which 144 were identified by more than one peptide. Several members
      of the immunologically important early secretory antigenic target-6 (ESAT-6)
      family of proteins were found to be major components. The majority of the
      identified proteins, 159 (62%), were predicted to be exported through the general
      secretory pathway. We experimentally verified that the signal peptides, which
      mediate translocation through the cell membrane, had been removed in 41 of the
      identified proteins, and in 35 of those, there was an AXA motif N-terminally to
      the cleavage site, showing that this motif is important for the recognition and
      cleavage of signal peptides in mycobacteria. A large fraction of the secreted
      proteins were unknown, suggesting that we have mapped an unexplored part of the
      exported proteome of M. tuberculosis. complement.

PMID- 17443847
TI  - Proteome-wide analysis of the serological response to vaccinia and smallpox.
AB  - The eradication of smallpox by vaccination with vaccinia virus was probably one
      of the greatest achievements of vaccinology. However, the immunological basis of
      this protection is not fully understood. To this end, we have used protein
      microarrays of the vaccinia (Western Reserve, WR) proteome to profile antibody
      reactivities after primary infection or boosting with the licensed smallpox
      vaccine, Dryvax, and with archival convalescent smallpox sera. Some 25 antigens
      were consistently recognized by Dryvax sera, of which half were envelope proteins
      (notably, H3, A13, B5, and D8). The remainder consisted mainly of core proteins
      (e.g. A10, L4, and I1), proteins involved in intracellular morphogenesis (A11,
      D13), and the A-type inclusion protein, WR148. Convalescent smallpox sera also
      detected vaccinia antigens on the array, consistent with the notion that there is
      serological cross-reactivity between these two orthopox species that underlies
      protection. Moreover, the profiles of immunodominant antigens recognized by
      variola-infected individuals and Dryvax vaccinees were indistinguishable. This is
      the first description of antibody-specificity profiles induced after smallpox
      infection. The array data indicate that a significant component of the antibody
      response is not involved in virus neutralization, although these antigens should
      be considered alongside the envelope proteins as potential candidates for
      diagnostic and vaccine applications.

PMID- 17443848
TI  - Duplex ultrasonography and varicose veins.

PMID- 17443849
TI  - Surgical volume and clinical outcome.

PMID- 17443850
TI  - Systematic review of dysplasia after restorative proctocolectomy for ulcerative
      colitis.
AB  - BACKGROUND: The aim of this systematic review was to assess the prevalence and
      site of dysplasia after restorative proctocolectomy (RPC) for ulcerative colitis
      (UC), and to identify risk factors that could be used in a surveillance
      programme. METHODS: Medical databases were searched for potentially relevant
      publications between 1978 and 2006. Studies that dealt with RPC for UC and
      postoperative surveillance were included. Two researchers independently performed
      study selection, quality assessment, data extraction and analysis. RESULTS:
      Twenty-three observational studies and case series were included, with a total of
      2040 patients. The pooled prevalence of confirmed dysplasia in the pouch, anal
      transitional zone or rectal cuff was 1.13 (range 0-18.75) per cent. The
      prevalence of high-grade dysplasia, low-grade dysplasia and indefinite for
      dysplasia was 0.15 (range 0-4.49), 0.98 (range 0-15.62) and 1.23 (range 0-25.28
      per cent) respectively. Dysplasia was equally frequent in the pouch and rectal
      cuff or anal transitional zone. Dysplasia and cancer identified before or at
      operation seemed to be significant predictors of the development of dysplasia.
      Pouchitis and duration of follow-up were not of predictive value. CONCLUSION:
      Although based on low-level evidence from uncontrolled studies, the prevalence of
      dysplasia observed after RPC was remarkable. A surveillance programme that takes
      into account the risk factors found is therefore advocated.

PMID- 17443851
TI  - Endovascular treatment of traumatic rupture of the thoracic aorta.
AB  - BACKGROUND: Traumatic rupture of the thoracic aorta is a life-threatening event.
      Open surgical repair is the 'gold standard', but is associated with high
      mortality and morbidity rates. Endovascular repair is emerging as a potentially
      safer alternative. METHODS: A systematic review was performed of all published
      literature on this subject, including the authors' own experience. Using
      Sumsearch, PubMed and cross-references, all published reports up to January 2006
      were identified, and analysed for injuries, perioperative morbidity, mortality,
      operating time, hospital stay and follow-up. RESULTS: A total of 284 patients
      were identified. Reported mortality rates range from 0 to 6 per cent. The
      procedure-related mortality rate is about 1.5 per cent. Some 6.7 per cent of all
      procedures were complicated by endoleak and the overall procedure-related
      morbidity rate was 14.4 per cent. These results are promising compared with those
      of open repair, but individual experience is limited and there may be some
      publication bias. CONCLUSION: Endovascular repair of traumatic rupture of the
      thoracic aorta seems to reduce morbidity and mortality in patients with multiple
      trauma. Ideally, both devices and experienced personnel should be available in
      trauma centres.

PMID- 17443852
TI  - Randomized clinical trial of effect of synbiotics, neomycin and mechanical bowel
      preparation on intestinal barrier function in patients undergoing colectomy.
AB  - BACKGROUND: The aim of this study was to investigate whether it is possible to
      modulate gut microflora and preserve intestinal barrier function during elective
      colorectal surgery by using combinations of oral antibiotics, synbiotics and
      mechanical bowel preparation (MBP). METHODS: Ninety-two patients were randomly
      assigned to one of four groups. Group 1 had MBP only, group 2 had neomycin + MBP,
      group 3 had synbiotics + neomycin + MBP, and group 4 had synbiotics + neomycin
      but no MBP. Changes in gut microflora were assessed by culturing nasogastric
      aspirates and polymerase chain reaction-denaturing gradient gel electrophoresis
      of faecal samples. Intestinal barrier function was determined by microbiological
      confirmation of bacterial translocation and measurement of intestinal
      permeability. The inflammatory response was monitored by measurement of serum C
      reactive protein and interleukin 6, and septic morbidity was recorded
      prospectively. RESULTS: Four patients were excluded owing to protocol violation,
      leaving 24 patients in group 1, 22 in group 2, 20 in group 3 and 22 in group 4
      for analysis. There was a significant decrease in Enterobacteriaceae in group 3
      compared with the other groups. Group 3 had a significantly lower incidence of
      translocation after bowel mobilization (P < 0.001). There was no significant
      difference between the groups in intestinal permeability, inflammatory response
      or septic morbidity. CONCLUSION: The combination of MBP, neomycin and synbiotics
      reduces the prevalence of faecal Enterobacteriaceae and bacterial translocation;
      however, this was not associated with a reduction in inflammatory response or
      septic morbidity in this study. Larger trials are needed before a change in
      practice can be recommended.

PMID- 17443854
TI  - Randomized clinical trial of the impact of early enteral feeding on postoperative
      ileus and recovery.
AB  - BACKGROUND: Postoperative convalescence is mainly determined by the extent and
      duration of postoperative ileus. This randomized clinical trial evaluated the
      effects of early oral feeding on functional gastrointestinal recovery and quality
      of life. METHODS: One hundred and twenty-eight patients undergoing elective open
      colorectal or abdominal vascular surgery participated in the trial. Of these, 67
      were randomized to a conventional return to diet, and 61 to a regimen allowing
      resumption of an oral diet as soon as tolerated (free diet group). RESULTS:
      Reinsertion of a nasogastric tube was necessary in 20 per cent of the free diet
      group and 10 per cent of the conventional group (P = 0.213). The complication
      rate was similar for both groups, as was return of gastrointestinal function. A
      normal diet was tolerated after a median of 2 days in the free diet group
      compared with 5 days in the conventional group (P < 0.001). Quality of life
      scores were similar in both groups. CONCLUSION: Early resumption of oral intake
      does not diminish the duration of postoperative ileus or lead to a significantly
      increased rate of nasogastric tube reinsertion. Tolerance of oral diet is not
      influenced by gastrointestinal functional recovery. As there is no reason to
      withhold oral intake following open colorectal or abdominal vascular surgery,
      postoperative management should include early resumption of diet.

PMID- 17443855
TI  - Long-term results of a randomized clinical trial of Shouldice, Lichtenstein and
      transabdominal preperitoneal hernia repairs.
AB  - INTRODUCTION: There is an ongoing debate about the preferred technique for
      inguinal hernia repair. In this randomized study the long-term results of
      Shouldice, Lichtenstein and transabdominal preperitoneal (TAPP) hernia repair
      were compared. METHODS: Some 280 men with a primary hernia were randomized
      prospectively to undergo Shouldice, tension-free Lichtenstein or laparoscopic
      TAPP repair. Patients were examined after 52 months to assess hernia recurrence,
      nerve damage, testicular atrophy and patient satisfaction. RESULTS: Hernia
      recurrence occurred in six patients after Shouldice repair, and in one patient
      each after Lichtenstein and TAPP repairs. All recurrences after tension-free
      repairs were diagnosed within the first year after surgery. Nerve injuries were
      significantly more frequent after open Shouldice and Lichtenstein repairs.
      Patient satisfaction was greatest after laparoscopic TAPP repair. CONCLUSION:
      Tension-free repair was superior to the non-mesh Shouldice technique. The open
      anterior approach to the groin was associated with demonstrable nerve injury, and
      laparoscopic TAPP repair was the most effective approach in the hands of an
      experienced surgeon.

PMID- 17443856
TI  - Oesophagectomy practice and outcomes in England.
AB  - BACKGROUND: The 2001 UK National Health Service guidance on improving outcomes
      recommended centralization of oesophageal resection. The aim of this study was to
      analyse national trends in oesophageal resection in England to determine whether
      centralization has occurred and its impact on outcomes. METHODS: The study used
      data from Hospital Episode Statistics for 1997-1998 to 2003-2004 and included
      patients who had resection for oesophageal cancer. The annual hospital volume was
      grouped into five categories based on the recommendation for annual volume for a
      designated centre. RESULTS: A total of 11 838 oesophageal resections were
      performed. The total number of hospitals performing resections decreased, mainly
      owing to a fall in the number of very low-volume hospitals (117 in 1997 to 45 in
      2003). The proportion of resections performed in very high-volume hospitals
      increased from 17.8 per cent during 1997-1999 to 21.9 per cent during 2002-2003
      (P < 0.001). The overall in-hospital mortality rate was 10.1 per cent, with a
      significant reduction over time (from 11.7 to 7.6 per cent; P < 0.001). The
      decline in mortality rate may be due to increased numbers of patients undergoing
      surgery in higher-volume hospitals. There was an increase in the annual number of
      new patients from 5672 to 6230 during the study, although a fall in the
      proportion of resections from 31.5 to 26.0 per cent (P < 0.001). CONCLUSION:
      Centralization and multidisciplinary team expertise partly explain the
      improvement in mortality rate, but changes in preoperative selection also play a
      part.

PMID- 17443857
TI  - Randomized clinical trial comparing botulinum toxin injections with 0.2 per cent
      nitroglycerin ointment for chronic anal fissure (Br J Surg 2007; 94: 162-167).

PMID- 17443859
TI  - Randomized clinical trial comparing feeding jejunostomy with nasoduodenal tube
      placement in patients undergoing oesophagectomy (Br J Surg 2007; 94: 31-35).

PMID- 17443861
TI  - Randomized clinical trial of Lichtenstein's operation versus mesh plug for
      inguinal hernia repair (Br J Surg 2007; 94: 36-41).

PMID- 17443863
TI  - Comparative study of modified release alpha-blocker exposure in elderly patients
      with fractures.
AB  - PURPOSE: Standard formulation alpha-blocker use has been associated with an
      increased risk of hypotension-related adverse events, particularly with
      cardiovascular indications and on treatment initiation. We investigated the
      association between those fractures that are commonly due to falls and modified
      release doxasozin exposure. METHODS: A case-control study using UK primary care
      records (the THIN database) showed that 6540 cases aged 50 years or older had a
      record of first fracture of the hip/femur, humerus or wrist after May 2001; 26
      495 controls had no fracture and were matched on practice, year of birth and sex.
      Exclusions for the primary analysis were previous benign prostatic hypertrophy
      (BPH), lower urinary tract symptoms (LUTS) or prostate cancer, major trauma at
      the time of the case's fracture, or a history of falls. Conditional logistic
      regression estimated the association between modified-release doxasozin treatment
      and the occurrence of fractures. RESULTS: No increased risk of fractures was
      associated with current use of modified-release doxasozin, adjusted odds ratios
      (ORs) 0.90 (95%CI 0.68, 1.19); previous use, adjusted OR 0.92 (95%CI 0.73, 1.16)
      or the start of a treatment episode (</=28 days), crude OR 0.57 (0.17, 1.92).
      Including those with a history of BPH, LUTS and prostatic carcinoma had little
      effect, adjusted OR for current use was 0.95 (95%CI 0.74, 1.21). No significant
      increased risk of fractures was associated with the start of standard preparation
      alpha-blockers, crude OR 1.42 (95%CI 0.65, 3.07). CONCLUSIONS: We found no
      association between modified-release doxasozin use and fractured hip/femur,
      humerus or wrist in those without a recent history of falls, or trauma.

PMID- 17443865
TI  - Surgical strategies for gastric cancer with synchronous peritoneal carcinomatosis
      (Br J Surg 2006; 93: 1530-1535).

PMID- 17443866
TI  - Intra-anal collagen injection for the treatment of faecal incontinence (Br J Surg
      2006; 93: 1514-1518).

PMID- 17443868
TI  - Patterns and prevalence of antidepressant drug use in the German state of Baden
      Wuerttemberg: a prescription-based analysis.
AB  - PURPOSE: Population-based data about patterns and prevalence of antidepressant
      drug use is limited in Europe and presently unavailable for Germany. Therefore,
      we have identified patterns and prevalence of antidepressant use among
      outpatients on a population-based scale in the German state of Baden
      Wuerttemberg. METHODS: We conducted a historical cohort study using a
      computerised prescription database referring to all members of the major German
      public health insurance company AOK. We assessed the prevalence of antidepressant
      drug use over a 3-year period, calculated the number of prescription items
      purchased per patient and compared first-line and second-line treatments.
      RESULTS: The 1-year prevalence of antidepressant drug use among more than
      4,000,000 health insurance members was 7.4% (male: 4.3%; female: 10.2%).
      Importantly, almost 40% of the patients received only a single prescription item
      from 2000 to 2002. Though the use of serotonin-reuptake inhibitors (SSRIs)
      markedly increased by about 65% within the study period, these are primarily used
      as second-line drugs and still much less frequently than St. John's wort or
      tricyclic antidepressants such as amitryptiline or doxepin. CONCLUSIONS: The
      prevalence of antidepressant drug use is higher than previously reported for
      other European countries. The preferred use of St. John's wort and tricyclics
      over SSRIs and other modern-type antidepressants in Germany is quite unique in
      Europe and different from the US. The identified drug use pattern leaves a major
      room for improvement in view of the numerous single prescription items purchased.

PMID- 17443870
TI  - Reactions of the HCN-tetramer with aldehydes.
AB  - The HCN-tetramer, a 'classic' of the prebiotic chemistry of HCN, is shown to
      undergo a remarkable reaction with acetaldehyde in slightly basic or neutral
      aqueous solution at room temperature. The reaction consists in an aldolization
      type C,C-bond formation, accompanied by a (presumably aldehyde-catalyzed)
      hydration of one of the two nitrile groups and the formation of two cyclic aminal
      type groupings, each of the latter incorporating an additional molecule of the
      aldehyde. Should this so far unexplored type of chemistry of the HCN-tetramer
      prove to have some generality, the finding might add a new dimension to the
      potential etiological relevance of this HCN-oligomer.

PMID- 17443871
TI  - On a hypothetical generational relationship between HCN and constituents of the
      reductive citric acid cycle.
AB  - Encouraged by observations made on the course of reactions the HCN-tetramer can
      undergo with acetaldehyde, I delineate a constitutional and potentially
      generational relationship between HCN and those constituents of the reductive
      citric acid cycle that are direct precursors of amino acids in contemporary
      metabolism. In this context, the robustness postulate of classical prebiotic
      chemistry is questioned, and, by an analysis of the (hypothetical) reaction-tree
      of a stepwise hydrolysis of the HCN-tetramer, it is shown how such a non-robust
      chemical reaction platform could harbor the potential for the emergence of
      autocatalytic cycles. It is concluded that the chemistry of HCN should be
      revisited by focussing on its non-robust parts in order to demonstrate its full
      potential as one of the possible roots of prebiotic self-organizing chemical
      processes.

PMID- 17443872
TI  - Chemistry and selection.
AB  - Life is the product of chemistry, which obeys deterministic laws, and of natural
      selection, which operates on variants offered to it by chance, but may, in a
      number of cases, have been provided with a sufficiently extensive array of
      variants to be optimizing. Thus, the origin and evolution of life have been
      largely shaped by the contingency of environmental conditions. The possibility
      remaining open for consideration is that certain critical conditions are
      sufficiently reproducible for life to arise and even to evolve into conscious,
      intelligent beings elsewhere in the universe.

PMID- 17443873
TI  - On the chemistry and evolution of the pioneer organism.
AB  - The theory of a chemo-autotrophic origin of life in a volcanic Iron-Sulfur World
      postulates the emergence of a pioneer organism within a flow of volcanic
      exhalations. The pioneer organism is characterized by a composite structure with
      an inorganic substructure and an organic superstructure. Within the surfaces of
      the inorganic substructure, iron, cobalt, nickel, and other transition-metal
      centers with sulfido, carbonyl, cyano, and other ligands are catalytically
      active, and promote the growth of the organic superstructure through carbon
      fixation, driven by the reducing potential of the volcanic exhalations. This
      pioneer organism is reproductive by an autocatalytic feedback effect, whereby
      some organic products serve as ligands for activating the catalytic metal centres
      whence they arise. This unitary structure-function relationship of the pioneer
      organism constitutes the 'Anlage' for two major strands of evolution:
      enzymatization and cellularization, whereby the upward evolution of life by
      increase of molecular complexity is grounded ultimately in the transition metal
      catalyzed, synthetic redox chemistry of the pioneer organism.

PMID- 17443874
TI  - Chemical aspects of synthetic biology.
AB  - Synthetic biology as a broad and novel field has also a chemical branch: whereas
      synthetic biology generally has to do with bioengineering of new forms of life
      (generally bacteria) which do not exist in nature, 'chemical synthetic biology'
      is concerned with the synthesis of chemical structures such as proteins, nucleic
      acids, vesicular forms, and other which do not exist in nature. Three examples of
      this 'chemical synthetic biology' approach are given in this article. The first
      example deals with the synthesis of proteins that do not exist in nature, and
      dubbed as 'the never born proteins' (NBPs). This research is related to the
      question why and how the protein structures existing in our world have been
      selected out, with the underlying question whether they have something very
      particular from the structural or thermodynamic point of view (for example, the
      folding). The NBPs are produced in the laboratory by the modern molecular biology
      technique, the phage display, so as to produce a very large library of proteins
      having no homology with known proteins. The second example of chemical synthetic
      biology has also to do with the laboratory synthesis of proteins, but, this time,
      adopting a prebiotic synthetic procedure, the fragment condensation of short
      peptides, where short means that they have a length that can be obtained by
      prebiotic methods; for example, from the condensation of N-carboxy anhydrides.
      The scheme is illustrated and discussed, being based on the fragment condensation
      catalyzed by peptides endowed with proteolitic activity. Selection during chain
      growth is determined by solubility under the contingent environmental conditions,
      i.e., the peptides which result insoluble are eliminated from further growth. The
      scheme is tested preliminarily with a synthetic chemical fragment-condensation
      method and brings to the synthesis of a 44-residues-long protein, which has no
      homology with known proteins, and which has a stable tertiary folding. Finally,
      the third example, dubbed as 'the minimal cell project'. Here, the aim is to
      synthesize a cell model having the minimal and sufficient number of components to
      be defined as living. For this purpose, liposomes are used as shell membranes,
      and attempts are made to introduce in the interior a minimal genome. Several
      groups all around the world are active in this field, and significant results
      have been obtained, which are reviewed in this article. For example, protein
      expression has been obtained inside liposomes, generally with the green
      fluorescent protein, GFP. Our last attempts are with a minimal genome consisting
      of 37 enzymes, a set which is able to express proteins using the ribosomal
      machinery. These minimal cells are not yet capable of self-reproduction, and this
      and other shortcomings within the project are critically reviewed.

PMID- 17443875
TI  - Errors and alternatives in prebiotic replication and catalysis.
AB  - The work on nonenzymatic nucleic acid replication performed by Leslie Orgel and
      co-workers over the last four decades, now extended by work on artificial
      selection of RNA aptamers and ribozymes, is generating some pessimism concerning
      the 'naked gene' theories of the origin of life. It is suggested here that the
      low probability of finding RNA aptamers and ribozymes within pools of random
      sequences is not as disquieting as the poor gain in efficiency obtained with
      increases in information content. As acknowledged by Orgel and many other
      authors, primitive RNA replication and catalysis must have occurred within
      already complex and dynamic environments. I, thus, propose to pay attention to a
      number of possibilities that bridge the gap between 'naked gene' theories, on one
      side, and metabolic theories in which complex systems self-propagate by growth
      and fragmentation, on the other side. For instance, one can de-emphasize
      nucleotide-by-nucleotide replication leading to long informational polymers, and
      view instead long random polymers as storage devices, from which shorter
      oligomers are excised. Catalytic tasks would be mainly performed by complexes
      associating two or more oligomers belonging to the same or to different chemical
      families. It is proposed that the problems of stability, binding affinity,
      reactivity, and specificity could be easier to handle by heterogeneous complexes
      of short oligomers than by long, single-stranded polymers. Finally, I point out
      that replication errors in a primitive replication context should include
      incorporations of alternative nucleotides with interesting, chemically reactive
      groups. In this way, an RNA sequence could be at the same time an inert sequence
      when copied without error, and a ribozyme, when a chemically reactive nucleotide
      is inadvertently introduced during replication.

PMID- 17443876
TI  - Ribozyme catalysis of metabolism in the RNA world.
AB  - In vitro selection has proven to be a useful means of explore the molecules and
      catalysts that may have existed in a primordial 'RNA world'. By selecting binding
      species (aptamers) and catalysts (ribozymes) from random sequence pools, the
      relationship between biopolymer complexity and function can be better understood,
      and potential evolutionary transitions between functional molecules can be
      charted. In this review, we have focused on several critical events or
      transitions in the putative RNA world: RNA self-replication; the synthesis and
      utilization of nucleotide-based cofactors; acyl-transfer reactions leading to
      peptide and protein synthesis; and the basic metabolic pathways that are found in
      modern living systems.

PMID- 17443877
TI  - A systematic review of the impact of volume of surgery and specialization on
      patient outcome (Br J Surg 2007; 94: 145-161).

PMID- 17443880
TI  - Role of circulating tumour cells in predicting recurrence after excision of
      primary colorectal carcinoma (Br J Surg 2007; 94: 96-105).

PMID- 17443881
TI  - Intractable mixtures and the origin of life.
AB  - Attempts to model the spontaneous chemistry which presumably preceded the origin
      of life on Earth commonly result in the production of intractably complex
      mixtures of organic compounds. It is, therefore, difficult to understand how any
      kind of evolutionary process might have begun. A number of potential solutions to
      this well-known and frustrating problem have been offered in the literature over
      the years. The present contribution briefly reviews and evaluates some of the
      more promising possibilities.

PMID- 17443882
TI  - From interstellar amino acids to prebiotic catalytic peptides: a review.
AB  - Amino acids were most likely available on the primitive Earth, produced in the
      primitive atmosphere or in hydrothermal vents. Import of extraterrestrial amino
      acids may have represented the major supply, as suggested by micrometeorite
      collections and simulation experiments in space and in the laboratory. Selective
      condensation of amino acids in water has been achieved via N-carboxy anydrides.
      Homochiral peptides with an alternating sequence of hydrophobic and hydrophilic
      amino acids adopt stereoselective and thermostable beta-pleated sheet structures.
      Some of the homochiral beta-sheets strongly accelerate the hydrolysis of
      oligoribonucleotides. The beta-sheet-forming peptides have also been shown to
      protect their amino acids from racemization. Even if peptides are not able to
      self-replicate, i.e., to replicate a complete sequence from the mixture of amino
      acids, the accumulation of chemically active peptides on the primitive Earth
      appears plausible via thermostable and stereoselective beta-sheets made of
      alternating sequences.

PMID- 17443883
TI  - The chemistry that preceded life's origin: a study guide from meteorites.
AB  - Carbonaceous meteorites are rare fragments of asteroids that contain organic
      carbon of diverse composition, various complexity, and whose lineage can in
      several instances be traced back to pre-solar environments. Their analyses offer
      a unique glimpse into the chemistry of the solar system that preceded life and
      may have been available to its emergence on the early Earth. While the
      heterogeneity of the organic materials of meteorites is indicative of random
      synthetic processes for their formation, some of their components have identical
      counterparts in the biosphere, and a group of meteoritic amino acids were found
      to display chiral asymmetry, a property known since the time of Pasteur to be
      inextricably linked to life's processes. The ability of these amino acids to act
      as asymmetric catalysts, as well as indications that molecular asymmetry in
      meteorites may not be limited to these compounds, encourage the suggestion of
      possible involvement of meteoritic material in the induction of selective traits
      in molecular evolution.

PMID- 17443884
TI  - Formamide chemistry and the origin of informational polymers.
AB  - Formamide (HCONH2) provides a chemical frame potentially affording all the
      monomeric components necessary for the formation of nucleic polymers. In the
      presence of the appropriate catalysts, and by moderate heating, formamide yields
      a complete set of nucleic bases, acyclonucleosides, and favors both
      phosphorylations and transphosphorylations. Physico-chemical conditions exist in
      which formamide favors the stability of the phosphoester bonds in nucleic
      polymers more than that of the same bonds in monomers. This property establishes
      'thermodynamic niches' in which the polymeric forms are favored. The hypothesis
      that these specific attributes of formamide allowed the onset of prebiotic
      chemical equilibria capable of Darwinian evolution is discussed.

PMID- 17443885
TI  - RNA: prebiotic product, or biotic invention?
AB  - Spectacular advances in structural and molecular biology have added support to
      the 'RNA world' hypothesis, and provide a mandate for chemistry to explain how
      RNA might have been generated prebiotically on the early earth. Difficulties in
      achieving a prebiotically plausible synthesis of RNA, however, have led many to
      ponder the question posed in the title of this paper. Herein, we review recent
      experimental work on the assembly of potential RNA precursors, focusing on
      methods for stereoselective C-C bond construction by aldolisation and related
      processes. This chemistry is presented in the context of a broader picture of the
      potential constitutional self-assembly of RNA. Finally, the relative
      accessibility of RNA and alternative nucleic acids is considered.

PMID- 17443886
TI  - Chemical etiology of nucleic acids: aminopropyl nucleic acids (APNAs).
AB  - Aminopropyl nucleic acids (APNAs) are constitutionally simple nucleic acid
      alternatives with one stereogenic center per nucleotide, and with the potential
      to hybridize with RNA and to exert catalytic functions. We have developed a
      protecting group strategy to synthesize APNAs, although in a not very efficient
      way. Isolation and purification of APNAs proved to be difficult. Their structures
      might be more suited to function as potential catalytic polymers than as
      information systems that may evolve into RNA.

PMID- 17443887
TI  - Nonenzymatic recombination of RNA: possible mechanism for the formation of novel
      sequences.
AB  - We report on the formation of novel RNA molecules in a recombination-like,
      nonenzymatic reaction proceeding in the complex of partially complementary RNA
      oligonucleotides under very simple conditions. Analysis of the isolated products
      demonstrated that at least 5% of the formed linkages are of the (natural) 3',5'
      phosphodiester type. We suggest that similar reactions could contribute to the
      development of the 'RNA world', but could also proceed in vivo within variously
      structured RNA or RNA complexes containing loops, bulges, or dangling ends,
      providing an emergence of novel RNA sequences.

PMID- 17443888
TI  - Addressing the problems of base pairing and strand cyclization in template
      directed synthesis: a case for the utility and necessity of 'molecular midwives'
      and reversible backbone linkages for the origin of proto-RNA.
AB  - Nucleic acid synthesis is precisely controlled in living organisms by highly
      evolved protein enzymes. The remarkable fidelity of information transfer realized
      between template and product strands is the result of both the spatial
      selectivity of the polymerase active site for Watson-Crick base pairs at the
      point of nucleotide coupling and subsequent proof-reading mechanisms. In the
      absence of naturally derived polymerases, in vitro template-directed synthesis by
      means of chemically activated mononucleotides has proven remarkably inefficient
      and error-prone. Nevertheless, the spontaneous emergence of RNA polymers and
      their protein-free replication is frequently taken as a prerequisite for the
      hypothetical 'RNA world'. We present two specific difficulties that face the de
      novo synthesis of RNA-like polymers in a prebiotic (enzyme-free) environment:
      nucleoside base selection and intramolecular strand cyclization. These two
      problems are inherent to the assumption that RNA formed de novo from pre
      existing, chemically-activated mononucleotides in solution. As a possible
      resolution to these problems, we present arguments and experimental support for
      our hypothesis that small molecules (referred to as 'molecular midwives') and
      alternative backbone linkages (under equilibrium control) facilitated the
      emergence of the first RNA-like polymers of life.

PMID- 17443889
TI  - Chemical primer extension: individual steps of spontaneous replication.
AB  - The replication of genetic information, as we know it from today's biology,
      relies on template-directed, polymerase-catalyzed extension of primers. It is
      known that short stretches of complementary RNA can form on templates in the
      absence of enzymes. This account summarizes recent work on efficient enzyme-free
      primer extension, both with 3'-amino-terminal deoxyribonucleotide primers and
      with primers made of unmodified RNA. Near-quantitative primer extension with half
      life times on the order of hours has been demonstrated by using
      azaoxybenzotriazolides of nucleotides and downstream-binding oligomers. Further,
      small non-nucleosidic substituents placed on the terminus of the template or the
      downstream-binding oligomer have been shown to increase the rate and fidelity of
      primer-extension reactions. Since all four templating bases (A, C, G, T/U) direct
      sequence-selective primer-extension steps, we feel that there is renewed hope
      that full, nonenzymatic replication from monomers may eventually be achieved.

PMID- 17443890
TI  - Conformational and chiral selection of oligonucleotides.
AB  - In view of a better understanding of chiral selection of oligonucleotides, we
      have studied the hybridization of D- and L-CNA (cyclohexane nucleic acids) and D-
      and L-DNA, with chiral D-beta-homo-DNA and achiral PNA (peptide nucleic acids).
      PNA hybridizes as well with D-DNA, L-DNA as with D-beta-homo-DNA. The structure
      of the PNA x D-beta-homo-DNA complex is different from the PNA x DNA duplexes. D
      CNA prefers D-DNA as hybridization partner, while L-CNA prefers D-beta-homo-DNA
      as hybridization partner. The conformation of the enantiomeric oligonucleotides D
      CNA and L-CNA in the supramolecular complex with D-DNA and D-beta-homo-DNA,
      respectively, is different. These data may contribute to the confirmation of a
      hypothesis of the existence of achiral informative polymers as RNA predecessor,
      and to the understanding of homochirality of nucleic acids.

PMID- 17443891
TI  - Preparation of guanine and diaminopurine from biuret. Part III.
AB  - Because of their potential prebiotic origin and relative chemical stability,
      urea, biuret, formic acid, and glycine amide might have played a role in the
      assembly process of purine bases. In this paper, we describe a short reaction
      path to purine nucleobases from these acyclic precursors. The formation of
      different purines was verified by UV and NMR spectroscopy, as well as by mass
      spectrometry.

PMID- 17443894
TI  - [Implication of 5-lipoxygenase/cysteinyl leukotriene receptors and
      histamine/histamine receptors in brain disease].

PMID- 17443895
TI  - [Transfection with 5-lipoxygenase/green fluorescence protein for evaluating
      injury-induced 5-lipoxygenase translocation to the nuclear membrane in PC12
      cells].
AB  - OBJECTIVE: To evaluate the translocation of 5-lipoxygenase (5-LOX)) after
      injuries by transfection with green fluorescence protein (GFP)/5-LOX in PC12
      cells. METHODS: PC12 cells were stably transfected with pEGFP-C2/5-LOX (GFP/5
      LOX) or pEGFP-C2 vectors (control). After treatment with oxygen-glucose
      deprivation (OGD), H(2)O(2) or NMDA, GFP/5-LOX localization in the cells was
      observed under a fluorescence microscope. Wild-type 5-LOX was determined by
      immunostaining after the treatment. RESULT: In the GFP/5-LOX-transfected cells,
      GFP/5-LOX was primarily localized in the nucleus; while in the GFP-transfected
      cells, GFP was localized in both the cytoplasm and nucleus. After OGD and
      H(2)O(2) treatments, GFP/5-LOX was translocated to the nuclear membrane in 50.6 %
      and 57.7% cells respectively. However, after NMDA treatment or in GFP-transfected
      cells, no translocation was observed. Wild-type 5-LOX was distributed in the
      nuclei and cytoplasm, and all the 3 treatments induced 5-LOX translocation to the
      nuclear membrane. CONCLUSION: In the PC12 cells stably transfected with GFP/5
      LOX, GFP/5-LOX is primarily distributed in the nuclei; the OGD-, H(2)O(2)- and
      NMDA-induced 5-LOX translocation exhibits different properties.

PMID- 17443896
TI  - [Effects of cysteinyl receptor agonist and antagonists on rat primary cortical
      neurons].
AB  - OBJECTIVE: To determine the effect of cysteinyl receptor agonist leukotriene D(4)
      (LTD(4)) and its antagonists on rat primary neurons. METHODS: In the primarily
      cultured rat cortical neurons, the neuron injury was evaluated by measuring
      intracellular calcium, 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl tetrazolium
      bromide (MTT) reduction, and propidium iodide (PI) and Hoechst 33258 staining.
      The in vitro ischemic injury was induced by oxygen-glucose deprivation (OGD) for
      1.5 h and reperfusion for 24 h. RESULT: LTD(4) (0.01-1 micromol/L) did not induce
      the elevation of intracellular calcium, neuron viability changes and neuron
      death. OGD-induced injury was not significantly ameliorated by the CysLT(1)
      receptor antagonists, pranlukast (0.2-10 micromol/L) and montelukast (0.2-10
      micromol/L), as well as by the CysLT(1)/CysLT(2) receptor non-selective
      antagonist, BAY u9773 (0.02-1 micromol/L). CONCLUSION: Neither agonist nor
      antagonists of cysteinyl receptors have the effects on the viability and ischemic
      like injury in rat primary neurons.

PMID- 17443897
TI  - [Cysteinyl leukotriene receptor 1 antagonist pranlukast modulates differentiation
      of SK-N-SH cells].
AB  - OBJECTIVE: To determine whether cysteinyl leukotriene receptor agonist LTD(4) and
      cysteinyl leukotriene receptor 1 (CysLT(1)) antagonist pranlukast affect the
      differentiation of human neuroblastoma SK-N-SH cells. METHODS: SK-N-SH cell
      morphological changes induced by LTD(4), pranlukast and LTD(4) + pranlukast were
      observed with retinoid acid (RA) as the positive control. The expressions of
      CysLT(1) and CysLT(2) receptors were detected by immunoblotting analysis, and the
      expression of microtubule-associated protein-2 (MAP-2), a neuron marker, was
      detected by fluorescent immunostaining. RESULT: The immunoblotting results showed
      that SK-N-SH cells expressed CysLT(1) receptor moderately, and CysLT(2) receptor
      highly. The morphological results showed that RA, pranlukast and LTD(4) +
      pranlukast induced the compaction of the cell bodies and the outgrowth of
      neurites, while LTD(4) had no significant effect. The immunostaining results
      showed that MAP-2 was distributed in the cell bodies in control or pranlukast
      treated cells; it was distributed in cell bodies and neuritis in RA-treated
      cells. Pranlukast increased the numbers of MAP-2-positive cells. CONCLUSION: The
      CysLT(1)receptor antagonist pranlukast modulates the differentiation of SK-N-SH
      cells.

PMID- 17443898
TI  - [A case of infant vitamin K deficiency first diagnosed at the Stomatology
      Department].

PMID- 17443899
TI  - [Involvement of endogenous histamine in modulatory effect of morphine on seizure
      susceptibility in mice].
AB  - OBJECTIVE: To investigate the modulatory effects of morphine on the
      susceptibility to pentylenetetrazole-induced seizures, and the involvement of
      endogenous histamine in this process. METHODS: Both the wild-type (WT) mice and
      histidine decarboxylase (a key enzyme for histamine biosynthesis) deficient (HDC
      KO) mice were subcutaneously injected with different doses of morphine, and 1
      hour later the pentylenetetrazole solution (1.5 %) was infused into the tail vein
      at a constant rate of 0.3 ml/min. The minimal dose of pentylenetetrazole (mg/kg)
      needed to induce myoclonic jerks and clonus convulsion was recorded as the
      thresholds of seizures. RESULT: In WT mice, morphine dose-dependently decreased
      the thresholds of both myoclonic jerks and clonus convulsion. In HDC-KO mice,
      morphine at 10 mg/kg only significantly decreased the threshold of myoclonic
      jerks from (38.6 +/-2.9)mg/kg to (32.5 +/-0.7)mg/kg, but had no significant
      effect on the threshold of clonus convulsion [from (51.8 +/-2.1)mg/kg to (47.6 +/
      1.2)mg/kg]. In addition, the value of decreased myoclonic jerks (15.8 +/-1.4)%
      and clonus convulsion (8.3 +/-0.9)% thresholds were much lower in HDC-KO mice
      than in WT mice [(26.1 +/-2.5)% and (20.8 +/-2.4)%, respectively]. CONCLUSION:
      Morphine can decrease the thresholds of pentylenetetrazole in induction of
      seizure, and the endogenous histamine may be involved in this process.

PMID- 17443900
TI  - [Effects of acute maximal electroshock and chronic transauricular kindled
      seizures on learning abilities in Sprague-Dawley rats].
AB  - OBJECTIVE: To investigate effects of acute maximal electroshock (MES) and chronic
      transauricular kindled seizures on learning abilities in Sprague-Dawley rats.
      METHODS: An acute MES was induced by giving an alternating current (150 mA, 0.2
      s) through ear-clip electrodes. Chronic transauricular kindled seizure was
      induced by repeated application of initially subconvulsive electrical stimulation
      (40 mA, 0.2 s) through ear-clip electrodes once every 24 h. An 8-arm radial maze
      (4 arms baited) was used to measure learning abilities. Histamine, glutamate and
      gamma-aminobutyric acid (GABA) were measured by high-performance liquid
      chromatography (HPLC). RESULT: In the acquisition learning process, an acute MES
      increased reference memory errors but not working memory errors. In addition, it
      increased GABA levels in the hippocampus. On the other hand, chronic
      transauricular kindled seizures increased both working and reference memory
      errors in retrieval memory process, and this lasted for at least 3 weeks. Chronic
      transauricular kindled seizures induced CA1 neuron damage and a decrease in
      histamine levels in the hippocampus. CONCLUSION: Different types of kindling
      seizure produce different effects on cognitive behavior: (1) an acute MES impairs
      learning ability, which may be associated with an abnormal plasticity and an
      increase of GABA in the hippocampus; (2) the chronic transauricular kindled
      seizure impairs retrieval memory mainly, which may be related to CA1 neuron
      damage and a decrease in histaminergic activity in the hippocampus.

PMID- 17443901
TI  - [Injection of saline into unilateral central piriform cortex inhibits amygdaloid
      kindled seizures in rats].
AB  - OBJECTIVE: To investigate the effect of microinjection of saline into unilateral
      central piriform cortex (cPC) on the generalized seizures in amygdaloid-kindled
      rats. METHODS: Different volumes of saline were injected into the right or left
      cPC of amygdaloid-kindled rats, and its effect on generalized seizures was
      observed. RESULT: Saline injection at different volumes 0.1 microl, 0.25 microl
      and 1 microl) significantly decreased the incidence and duration of generalized
      seizures (P<0.05), the anticonvulsant effect lasted for up to 10 d. In addition,
      10 min after ipsilateral injection of saline the generalized seizure thresholds
      were significantly increased; while this effect was observed 30 min later when
      contralateral injection was used. CONCLUSION: Unilateral saline injection into
      cPC has a significant anticonvulsant effect, which might be used for treatment of
      human temporal lobe epilepsy in the future.

PMID- 17443903
TI  - [Chronic mild stress stimulates nitric oxide production in rat brain cortex and
      hippocampus].
AB  - OBJECTIVE: To evaluate the nitric oxide (NO) levels in rat brain cortex and
      hippocampus after chronic mild stress. METHODS: Sixteen male Sprague-Dawley rats
      were allocated into control group and model group randomly. Model rats were
      induced by consecutive chronic mild stress; weight gain, open field test and
      sucrose solution consumption were investigated before and after procedure. Nitric
      oxide contents in prefrontal cortex and hippocampus were determined by
      spectrophotometric assays. RESULT: Decreased locomotion, loss of interest and
      anhedonia were observed in chronic mild stress rat model group. Nitric oxide
      contents in prefrontal cortex and hippocampus were significantly higher in
      chronic mild stress group [(31.00 +/-2.55)nmol/mg.pro and (38.11 +/
      1.73)nmol/mg.pro, respectively] than those in control group [(26.97 +/
      1.38)nmol/mg.pro and (36.06 +/-0.87)nmol/mg.pro, respectively] (P <0.05).
      CONCLUSION: Chronic stress can stimulate NO release, and dysfunction of nitric
      oxide pathway may be involved in development of depression.

PMID- 17443902
TI  - [Reversing effect of histamine on neurotoxicity induced by beta-amyloid1-42].
AB  - OBJECTIVE: To investigate the effects of histamine on the neurotoxicity induced
      by beta-amyloid(1-42)(Abeta42) in rat phaeochromocytoma (PC12) cells. METHODS:
      The in vitro model of Alzheimer's disease was constructed with A beta42-treated
      PC12 cells. Cell morphology and MTT assay were used to evaluate the cell toxicity
      and histamine effects. The different histamine antagonists were applied to
      investigate the involvement of receptor subtypes. RESULT: The neurotoxicity was
      induced by A beta42 in a concentration-dependent manner, which was reversed by
      histamine at concentration of 10(-7), 10(-6) mol/L. The effect was reversed by
      H(2) antagonist zolantidine and H(3)antagonist clobenpropit, but not by H(1)
      antagonist diphenhydramine. CONCLUSION: Histamine reduces neurotoxicity induced
      by beta-amyloid(1-42), which may be mediated by H(2) and H(3)receptors.

PMID- 17443904
TI  - [Live imaging and quantitative analysis of dendritic development of cultured rat
      hippocampal neurons].
AB  - OBJECTIVE: To measure mobility of dendritic filopodia, complexity of dendritic
      arborization using method of live imaging in cultured rat hippocampal neurons and
      to analyze their morphological characters quantitatively. METHODS: Vectors
      expressing Green Fluorescent Protein- Fibrous Actin (GFP-F-Actin) and F-GFP were
      co-transfected into cultured rat hippocampal neurons at 5 d in vitro (DIV 5).
      Neurons expressing GFP were photographed and analyzed with Metamorph software.
      RESULT: Dendritic filopodia was observed to move actively from DIV 7 to DIV 9.
      The mean density of filopodia was (10.78 +/-3.78)/100 microm, (10.68 +/-2.96)/100
      microm and (9.99 +/-3.67)/100 microm (P >0.05), and there were (30.18 +/-14.03)%
      to (87.36 +/-20.88)% filopodia were mobile (P <0.001). During DIV 7-DIV 14, the
      total length of dendritic branches grew from (410.74 +/-185.98) microm to
      (1238.21 +/-418.32)microm (P <0.001) and the number of dendritic branches
      increased from 18.93 +/-7.23 to 33.60 +/-10.46 (P<0.001). The density of spine
      was (37.17 +/-6.46)/100 microm at DIV 14. CONCLUSION: The combination of live
      imaging with quantitative analysis is a useful method to study dendritic
      morphological development in vitro, including indicators of dendritic filopodia,
      dendritic arborization and spines.

PMID- 17443905
TI  - [Expression of RAG-1 in brain during mouse development].
AB  - OBJECTIVE: To investigate the expression of recombination activating gene-1 (RAG
      1) and its localization in the mouse brain during the embryonic development.
      METHODS: The brain tissues of E (embryonic day) 11, E13, E15, E17, E19, P0 (the
      birth day) and adult mice were taken, the total RNA of brains were extracted and
      the changes of RAG-1 expression were detected with the method of RT-PCR. The
      freeze sections of brain tissues from each group were stained with
      immunohistochemistry method. RESULT: The expression of RAG-1 persisted from E11
      to P0 brain and was steadily increased from E11 to E19; the results of RT-PCR
      were similar to that of immunohistochemistry. The positive-cells mainly appeared
      in the nucleus amygdalae, hypothalamus, thalamus and hippocampus at developmental
      stage. The expression began to appear in ventricular zone (VZ) and intermediate
      zone (IZ) of telecephalic vesicle, then gradually increased in subventricular
      zone (SVZ), corticle plate (CP) and subcorticle plate (SP). CONCLUSION: The
      expression of RAG-1 in mouse embryonic brain tissue is higher than that in the
      adult mouse, which may be related to the process of neuron development.

PMID- 17443906
TI  - [A skilled reaching test for evaluating long-term neurological deficits after
      focal cerebral ischemia in mice].
AB  - OBJECTIVE: To determine whether the skilled reaching test is an objective method
      for evaluating long-term neurological deficits after focal cerebral ischemia in
      mice. METHODS: In a reaching box, mice were trained to reach food pellets with
      their left forelimb through a 0.5 cm slit for 3 weeks. Then focal cerebral
      ischemia was induced by occluding the right middle cerebral artery, and the
      percentage of success in obtaining food was observed for 4 weeks. In comparison,
      the neurological deficit score, the holding angle in an inclined board test, and
      right turns in a corner test were simultaneously performed. At the end of the
      experiments, brain infarcts and neuron densities were determined. RESULT: After
      focal cerebral ischemia, the percentage of success in the reaching test was
      reduced, the right turns in the corner test were increased, the neurological
      deficit score was increased, and the holding angle in the inclined board test was
      reduced as well. The holding angle recovered 5 d after ischemia, whereas other 3
      indicators remained abnormal until 4 weeks. At the end of the experiments, the
      brain infarct volumes were increased, and the neuron densities in the cortex,
      hippocampal CA1 region and striatum were reduced in ischemic mice. CONCLUSION:
      The skill reaching test is an objective and stable method for evaluating long
      term neurological deficits after focal cerebral ischemia in mice.

PMID- 17443907
TI  - [Impact of highly active antiretroviral therapy on plasma MCP-1 and MSP in AIDS
      patients].
AB  - OBJECTIVE: To study the effect of highly active antiretroviral therapy (HAART) on
      plasma levels of MSP and MCP-1 in AIDS patients. METHODS: Forty Chinese AIDS
      patients were treated with HAART for 3 months and 84 German AIDS patients with
      HAART for 3 to 6 years. The pre-treatment and post-treatment plasma levels of MSP
      and MCP-1 were measured by enzyme-linked immunosorbent assay (ELISA), and their
      correlations with CD4+ cell counts and viral loads were analyzed. RESULT: The
      mean levels of MCP-1 were significantly higher and MSP were significantly lower
      in HIV-infected patients compared with the HIV-negative controls (P <0.01). After
      HAART for three months, there were no significant changes in the levels of these
      cytokines. But after long-term HAART (for 3 to 6 y), the level of MCP-1 was
      increased and that of MSP decreased significantly (P<0.01). There was a negative
      correlation between MSP and MCP-1 levels, and the same for MSP level and CD4+
      cell counts; while there was a positive correlation between MCP-1 levels and CD4+
      cell counts. CONCLUSION: The changed plasma levels of MSP and MCP-1 are
      associated with HIV-1 infection and HAART may reverse the levels of these two
      cytokines.

PMID- 17443908
TI  - [Analysis on bioactivity of HIV-1 integrase by ELISA method].
AB  - OBJECTIVE: To develop an ELISA-based method for analyzing biologic activities of
      HIV-1 integrase and for high throughput screening of integrase inhibitors.
      METHODS: After expression, renaturation and purification of integrase, the
      bioactivity of integrase and the inhibition of luffin-a were evaluated with an in
      vitro assay based on biotin-avidin EILSA and chemiluminescent substrates. RESULT:
      (1) The specific activity of the purified integrase was 54.92 units/mg of
      protein. (2)IC(50) (concentration causing 50% inhibition of integrase) of luffin
      a was (0.63 +/- 0.026) micromol/L. CONCLUSION: The non-radioactive assay can be
      used for analysis of bioactivities and high throughput screening of inhibitors of
      HIV-1 integrase.

PMID- 17443909
TI  - [Polymorphism of five X-STR loci in Chinese Achang ethnic group].
AB  - OBJECTIVE: To investigate the genetic polymorphism and applied value in forensic
      medicine of five short tandem repeats (STRs) loci(DXS7130, DXS7132, DXS7133,
      DXS6804 and DXS8378) on X-chromosome in Achang ethnic group. METHODS: Allele
      frequency and genotype distribution of five X-STR loci among 100 unrelated
      individuals from Achang ethnic group were analyzed by PCR following
      polyacrylamide gel electrophoresis and silver staining. Hardy-Weinberg
      equilibrium of females was tested and forensic parameters were calculated.
      RESULT: All the five STR loci were polymorphic in Achang ethnic group. Chi-square
      test indicated that genotype distribution of females was in accordance with Hardy
      Weinberg equilibrium. CONCLUSION: These results enrich Chinese genetic database
      and can be applied to individual identification, paternity testing and population
      genetics.

PMID- 17443910
TI  - [Mechanism of apoptosis-inducing effects of dopamine on K562 leukemia cells].
AB  - OBJECTIVE: To investigate the mechanism of the apoptosis-inducing effects of
      dopamine on K562 leukemia cells. METHODS: K562 cells were treated with DP2785,
      the dopamine receptors were detected with fluorescence spectrophotometer, UV
      spectrophotometer and fluorescence microscope; the contents of cAMP in K562 cells
      were measured; and the subtypes of dopamine receptor on K562 cells were analyzed
      by receptor blocking. RESULT: The existence of dopamine receptors in K562 cells
      was demonstrated by fluorescence microscopy, UV spectrophotometer and
      fluorescence spectrophotometer. Dopamine enhanced the contents of cAMP in K562
      cells. Dopamine receptors were blocked by both D1 and D2 antagonists. CONCLUSION:
      D1 and D2 dopamine receptors may be involved in dopamine-induced apoptosis of
      K562 cells, and dopamine can also increase the contents of cAMP in K562 cells.

PMID- 17443911
TI  - [Management of sinonasal inverted papilloma: endoscopic approach and lateral
      rhinotomy].
AB  - OBJECTIVE: To compare endoscopic approach with lateral rhinotomy for treatment of
      the sinonasal inverted papilloma in terms of advantage, indications and
      limitations of the procedures. METHODS: Eighty-six cases with inverted papilloma
      were reviewed retrospectively, among which 23 cases underwent transnasal
      endoscopic procedures including 10 combined with Caldwell-Luc intervention, and
      63 cases underwent lateral rhinotomy. The follow-up period ranged from 11 - 36 m
      (mean 23 m). The data were processed statistically by SPSS 10.0 software. RESULT:
      Both procedures permitted removal of most sinonasal inverted papilloma. The
      endoscopic surgery provided an excellent visualization, and preserved a vital
      anatomic structure and left no facial scar. Lateral rhinotomy was associated with
      postoperative facial scar or deformity. The recurrence rate in lateral rhinotomy
      group was 9.5% and in endoscopic approach was 13% (P >0.05). CONCLUSION:
      Endoscopic approach is favored for the treatment of non-massively extending
      sinonasal inverted papilloma because of an acceptable recurrence and a better
      cosmetic results.

PMID- 17443912
TI  - [Carnosine and diseases of central nervous system].
AB  - The naturally-occurring dipeptide carnosine (beta-alanyl-L-histidine) is found
      exclusively in animal tissues, such as brain and skeletal muscle tissues.
      Carnosine is a potent hydrophilic antioxidant, antiglycating agent, reactive
      oxygen species scavenger and pH-buffer. Recent reports suggest that carnosine has
      potential therapeutic applications in many diseases of central nervous system,
      such as Alzheimer's disease, Parkinson's disease and cerebral ischemic diseases.
      To investigate the relationship between carnosine and diseases of central nervous
      system, and to research and develop carnosine drugs will shed light on a new way
      for treatment of diseases of central nervous system.

PMID- 17443913
TI  - [Advances in study of structures and functions of conantokins].
AB  - Conantokin is a distinct family of conotoxin superfamily. Its members share
      considerable overall sequence homology. Their defining attributes include a high
      relative content of gamma-carboxyglutamic acid (Gla). They are generally devoid
      of disufide-loop contrasted with other conotoxins (except for conantokin-R). Upon
      binding to metal ions, the content of alpha-helix conformation increases in
      different degrees. They inhibit NMDA (N-methyl-D-aspartate) receptors; moreover,
      different conantokin species present different NMDA receptor subunit specificity.
      It can induce sleep-like symptoms in young mice when delivered intracranially.
      Analysis of sequences and structures indicates that the high conserved residues
      of these peptides are determinative in their structures and functions. In this
      article, the relationships of their structures and functions are reviewed in
      detail.

PMID- 17443914
TI  - On call. I am 57 years old, and as far as I know, my health is excellent. At my
      last check-up, my doctor said that I was in perfect health except that my
      cholesterol was too high. Please tell me what you think of these results:
      cholesterol 243, LDL cholesterol 162, HDL cholesterol 68, and triglycerides 86.
      Everything else was "normal".

PMID- 17443915
TI  - I have a 40-inch waist. Can my waist size tell me something about my risk of
      suffering a heart attack?

PMID- 17443916
TI  - I've been suffering from chronic constipation, but I heard a recent study found
      that fiber doesn't help. What can I do?

PMID- 17443917
TI  - [Picture of the month: bone scintigraphy].

PMID- 17443918
TI  - [Postoperative mortality].

PMID- 17443919
TI  - [The recommended intake of vitamin D should be increased].

PMID- 17443920
TI  - [Antidepressive agents versus Viagra--or better treatment of mature men].

PMID- 17443921
TI  - [Neonatal and pediatric intensive therapy in Denmark today].

PMID- 17443922
TI  - [Back to nepotism?].

PMID- 17443923
TI  - The influence of different error estimates in the detection of postoperative
      cognitive dysfunction using reliable change indices with correction for practice
      effects.
AB  - The reliable change index (RCI) expresses change relative to its associated
      error, and is useful in the identification of postoperative cognitive dysfunction
      (POCD). This paper examines four common RCIs that each account for error in
      different ways. Three rules incorporate a constant correction for practice
      effects and are contrasted with the standard RCI that had no correction for
      practice. These rules are applied to 160 patients undergoing coronary artery
      bypass graft (CABG) surgery who completed neuropsychological assessments
      preoperatively and 1 week postoperatively using error and reliability data from a
      comparable healthy nonsurgical control group. The rules all identify POCD in a
      similar proportion of patients, but the use of the within-subject standard
      deviation (WSD), expressing the effects of random error, as an error estimate is
      a theoretically appropriate denominator when a constant error correction,
      removing the effects of systematic error, is deducted from the numerator in a
      RCI.

PMID- 17443924
TI  - Executive dysfunction and memory in older patients with major and minor
      depression.
AB  - Executive function, known to be impaired during late-life depression, is
      dependent on frontostriatal pathways. Memory is also frequently observed to be
      impaired among late-life depressed patients, so we assessed the possibility that
      executive function mediates the learning and recall deficit as a "downstream"
      effect of the frontostriatal compromise in executive function. A cross-sectional
      sample of minor and major depressed patients (N = 95) and nondepressed volunteers
      (N = 71), screened for other Axis I disorders, dementia, medical comorbidity and
      severity of depression, completed a neuropsychological battery that included the
      California Verbal Learning Test (CVLT) and other tests selected for convergent
      and divergent validity testing. Depressed patients differed from controls on
      learning the word list and on related and unrelated executive tasks. Executive
      function was a mediator for depressed patients verbal learning scores (z = -2.67,
      p = .01). A nonverbal executive score also mediated verbal learning (z = -2.18, p
      = .03) indicating convergent validity of executive dysfunction during verbal
      learning exercises. In conclusion, the verbal memory deficits typically
      attributed to late-life depression may result from impaired executive functioning
      during the learning phase of the recall task.

PMID- 17443925
TI  - Readers' and author's responses to "Physicians of the future will use online
      content to guide their decisions. The future is now!".

PMID- 17443926
TI  - Readers respond to "Readers respond to 'End the war on obesity: make peace with
      your patients' ".

PMID- 17443927
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443928
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443929
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443930
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443931
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443932
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443933
TI  - Hypoactive delirium: assessing the extent of the problem.

PMID- 17443934
TI  - Clarifying the data on double-effect.

PMID- 17443935
TI  - The use of transdermal rotigotine in a patient with advanced Parkinson's disease
      and dysphagia.

PMID- 17443936
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443937
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443938
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443939
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443940
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443941
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443942
TI  - Readers respond to "Advanced practice nurses say 'No' to a mandatory Doctor of
      Nursing Practice degree".

PMID- 17443943
TI  - National Institutes of Health implements electronic grant submission.

PMID- 17443944
TI  - NIH funds final Nanomedicine Development Centers.

PMID- 17443946
TI  - Dr. Rudo responds in Dr. Ronald S. Carlson's January 2007 rebuttal.

PMID- 17443947
TI  - [The Medical Code of Practice: clear reasons for existing, benefit less certain].

PMID- 17443948
TI  - [An asymmetrical face due to torticollis in two young children].

PMID- 17443949
TI  - [An asymmetrical face due to torticollis in two young children].

PMID- 17443950
TI  - Aphids do not attend to leaf colour as visual signal, but to the handicap of
      reproductive investment.
AB  - The evolution of visual warning signals is well known in animals but has received
      scant attention in plants. The coevolutionary hypothesis is the most influential
      hypothesis on warning signals in plants proposing that red and yellow leaf
      colours in autumn signal defensive strength to herbivores. So far, evidence in
      support of the hypothesis, which assumes a coevolutionary origin of autumnal leaf
      colours, is correlative and open to alternative explanations. We therefore tested
      the coevolutionary hypothesis experimentally by colouring the leaves either red
      or green of same-aged mountain ash (Sorbus aucuparia) individuals. We monitored
      the response of winged aphids to leaf colour using insect glue on branches with
      natural and artificial leaf colours in each individual. In contrast to the
      prediction of the coevolutionary hypothesis, aphid numbers did not differ between
      the individuals with artificial green or artificial red leaves. Likewise, at the
      within-plant level, aphids did not colonize branches with natural green leaves
      preferentially. However, we suggest that plants emitted warning signals because
      aphids colonized the hosts non-randomly. We found a strong positive correlation
      between aphid numbers and fruit production, suggesting an allocation trade-off
      between investment in plant defence and reproduction. Our study demonstrates that
      aphids use warning signals or cues in host selection, probably volatiles, but
      that they did not use leaf colour.

PMID- 17443951
TI  - Male swordtails court with an audience in mind.
AB  - Females are usually considered to be the target of male courtship behaviour. In
      nature, however, social interactions rarely occur without other observers; thus,
      it is conceivable that some male courtship behaviours are directed not towards
      females, but rather towards male rivals. The northern swordtail, Xiphophorus
      birchmanni, is a freshwater fish found in high densities in natural streams.
      Males court by swimming close to and in parallel with the female, raising their
      large sail-like dorsal fin, and quivering briefly. Here, we show that females
      prefer males that display small dorsal fins to those with large ones, and that
      males are less aggressive to other males with large dorsal fins. Male swordtails
      also raise their dorsal fins more frequently when courting in the presence of
      other males. These results suggest that, despite female avoidance of large dorsal
      fins, males that raise their fin during courtship benefit by intimidating
      potential competitors; the intended receivers of this signal are thus males, not
      females. Intrasexual selection can therefore offset the forces of intersexual
      selection, even in a courtship display.

PMID- 17443952
TI  - Representational signalling in birds.
AB  - Some animals give specific calls when they discover food or detect a particular
      type of predator. Companions respond with food-searching behaviour or by adopting
      appropriate escape responses. These signals thus seem to denote objects in the
      environment, but this specific mechanism has only been demonstrated for monkey
      alarm calls. We manipulated whether fowl (Gallus gallus) had recently found a
      small quantity of preferred food and then tested for a specific interaction
      between this event and their subsequent response to playback of food calls. In
      one treatment, food calls thus potentially provided information about the
      immediate environment, while in the other the putative message was redundant with
      individual experience. Food calls evoked substrate searching, but only if the
      hens had not recently discovered food. An identical manipulation had no effect on
      responses to an acoustically matched control call. These results show that
      chicken food calls are representational signals: they stimulate retrieval of
      information about a class of external events. This is the first such
      demonstration for any non-primate species. Representational signalling is hence
      more taxonomically widespread than has previously been thought, suggesting that
      it may be the product of common social factors, rather than an attribute of a
      particular phylogenetic lineage.

PMID- 17443953
TI  - The impact of climatic variation on the opportunity for sexual selection.
AB  - Many studies have demonstrated influences of climatic variation on a variety of
      ecological processes, however, its impact on the potent evolutionary force of
      sexual selection has largely been ignored. The intensity of sexual selection is a
      fundamental parameter in animal populations, which depends upon the degree of
      polygamy and will probably be influenced by the impact of local climatic
      variation upon 'environmental potential for polygamy'. Here, we provide evidence
      of a direct effect of local climatic variation on the intensity of sexual
      selection, by showing a clear correlation between local weather conditions and
      inter-annual changes in the degree of polygamy in a long-term study of colonially
      breeding grey seals (Halichoerus grypus). Our results show that changes in local
      weather conditions alter the annual proportion of males contributing to the
      effective population size (Ne) by up to 61%. Consequently, over the 'lifetime' of
      a cohort, a broader range of individuals will contribute genetically to the next
      generation if local weather conditions are variable. In the context of predicted
      future changes in climatic variation, these findings have broad implications for
      population genetics of socially structured animal systems through the major
      influence that the degree of polygamy has upon Ne.

PMID- 17443954
TI  - Continent-wide variation in feather colour of a migratory songbird in relation to
      body condition and moulting locality.
AB  - Understanding the causes of variation in feather colour in free-living migratory
      birds has been challenging owing to our inability to track individuals during the
      moulting period when colours are acquired. Using stable-hydrogen isotopes to
      estimate moulting locality, we show that the carotenoid-based yellow-orange
      colour of American redstart (Setophaga ruticilla) tail feathers sampled on the
      wintering grounds in Central America and the Caribbean is related to the location
      where feathers were grown the previous season across North America. Males that
      moulted at southerly latitudes were more likely to grow yellowish feathers
      compared with males that moulted more orange-red feathers further north.
      Independent samples obtained on both the breeding and the wintering grounds
      showed that red chroma-an index of carotenoid content-was not related to the mean
      daily feather growth rate, suggesting that condition during moult did not
      influence feather colour. Thus, our results support the hypothesis that feather
      colour is influenced by ecological conditions at the locations where the birds
      moulted. We suggest that these colour signals may be influenced by geographical
      variation in diet related to the availability of carotenoids.

PMID- 17443955
TI  - A multiple-site similarity measure.
AB  - Similarity measures are among the most intuitive and common measures for
      comparing two or more sites, or samples, with respect to their species overlap. A
      restriction of similarity measures is that they are limited to pairwise
      comparisons even in a multiple-site study. This work presents a multiple-site
      similarity measure that makes use of information on species shared by more than
      two sites and avoids the problem of covariance between pairwise similarities in a
      multiple-site study. Further, we show that our multiple-site similarity measure
      is related to beta-diversity measures such as Whittaker's beta-diversity.
      Similarity measures can also be used as descriptors of effective specialization
      of insects to host species by measuring similarity from host observations.
      Finally, we show that multiple-site similarity and host specificity are two sides
      of the same coin.

PMID- 17443956
TI  - Interspecific transmission of endosymbiotic Spiroplasma by mites.
AB  - The occurrence of closely related strains of maternally transmitted endosymbionts
      in distantly related insect species indicates that these infections can colonize
      new host species by lateral transfer, although the mechanisms by which this
      occurs are unknown. We investigated whether ectoparasitic mites, which feed on
      insect haemolymph, can serve as interspecific vectors of Spiroplasma poulsonii, a
      male-killing endosymbiont of Drosophila. Using Spiroplasma-specific primers for
      PCR, we found that mites can pick up Spiroplasma from infected Drosophila
      nebulosa females and subsequently transfer the infection to Drosophila
      willistoni. Some of the progeny of the recipient D. willistoni were infected,
      indicating successful maternal transmission of the Spiroplasma within the new
      host species. However, the transmission rate of the infection from recipient
      flies to their offspring was low, perhaps due to low Spiroplasma density in the
      recipient flies.

PMID- 17443957
TI  - Neural evolution in the bat-free habitat of Tahiti: partial regression in an anti
      predator auditory system.
AB  - Noctuid moths endemic to the mountains of Tahiti have evolved in an environment
      without bats and these insects have lost a defensive behaviour against these
      predators, the acoustic startle response (ASR). The ASR in noctuid moths is
      presumed to be activated by a single auditory receptor neuron (A2 cell) and we
      report that while this cell still exists in endemic species and possesses similar
      sensitivity thresholds compared to the A2 cell of recently introduced species, it
      exhibits reduced firing activity to ASR-evoking sounds. This partial neural
      regression suggests that the evolutionary disappearance of the ASR in these
      insects is incomplete and that sensoribehavioural integration decays gradually
      following the removal of stabilizing selective forces.

PMID- 17443958
TI  - Conflict between direct and indirect benefits of female choice in desert
      Drosophila.
AB  - Identifying the factors that contribute to the adaptive significance of mating
      preferences is one major goal of evolutionary research and is largely unresolved.
      Both direct and indirect benefits can contribute to mate choice evolution.
      Failure to consider the interaction between individual consequences of mate
      choice may obscure the opposing effects of individual costs and benefits. We
      investigate direct and indirect fitness effects of female choice in a desert fly
      (Drosophila mojavensis), a species where mating confers resistance to desiccation
      stress. Females prefer males that provide a direct benefit: greater resistance to
      desiccation stress. Mating preferences also appear to have indirect consequences:
      daughters of preferred males have lower reproductive success than daughters of
      unpreferred males, although additional experimentation will be needed to
      determine if the indirect consequences of female preferences actually arise from
      'sexually antagonistic' variation. Nevertheless, the results are intriguing and
      are consistent with the hypothesis that an interaction between direct and
      indirect benefits maintains sexually antagonistic variation in these desert
      flies: increased desiccation resistance conferred by mating might offset the cost
      of producing low-fecundity daughters.

PMID- 17443959
TI  - Spatial genetic analysis and long-term mark-recapture data demonstrate male
      biased dispersal in a snake.
AB  - Dispersal is an important life-history trait, but it is notoriously difficult to
      study. The most powerful approach is to attack the problem with multiple
      independent sources of data. We integrated information from a 14-year demographic
      study with molecular data from five polymorphic microsatellite loci to test the
      prediction of male-biased dispersal in a common elapid species from eastern
      Australia, the small-eyed snake Rhinoplocephalus nigrescens. These snakes have a
      polygynous mating system in which males fight for access to females. Our
      demographic data demonstrate that males move farther than females (about twice as
      far on average, and about three times for maximum distances). This sex bias in
      adult dispersal was evident also in the genetic data, which showed a strong and
      significant genetic signature of male-biased dispersal. Together, the genetic and
      demographic data suggest that gene flow is largely mediated by males in this
      species.

PMID- 17443960
TI  - No evidence of inbreeding avoidance in a polygynous ungulate: the reindeer
      (Rangifer tarandus).
AB  - In polygynous species, mate choice is an integrated part of sexual selection.
      However, whether mate choice occurs independently of the genetic relatedness
      among mating pairs has received little attention, although inbreeding may have
      fitness consequences. We studied whether genetic relatedness influenced females'
      choice of partner in a highly polygynous ungulate--the reindeer (Rangifer
      tarandus)--in an experimental herd during two consecutive rutting seasons; the
      herd consisting of 75 females in 1999 and 74 females in 2000 was exposed to three
      4.5-year-old adults and three 1.5-year-old young males, respectively. The
      females' distribution during peak rut was not influenced by their genetic
      relatedness with the dominant males of the mating groups. Further, genetic
      relatedness did not influence the actual choice of mating partner. We conclude
      that inbreeding avoidance through mating group choice as well as choice of mating
      partner, two interconnected processes of female mate choice operating at two
      different scales in space and time, in such a highly female-biased reindeer
      populations with low level of inbreeding may not occur.

PMID- 17443961
TI  - The adaptive significance of ontogenetic colour change in a tropical python.
AB  - Ontogenetic colour change is typically associated with changes in size,
      vulnerability or habitat, but assessment of its functional significance requires
      quantification of the colour signals from the receivers' perspective. The
      tropical python, Morelia viridis, is an ideal species to establish the functional
      significance of ontogenetic colour change. Neonates hatch either yellow or red
      and both the morphs change to green with age. Here, we show that colour change
      from red or yellow to green provides camouflage from visually oriented avian
      predators in the different habitats used by juveniles and adults. This reflects
      changes in foraging behaviour and vulnerability as individuals mature and
      provides a rare demonstration of the adaptive value of ontogenetic colour change.

PMID- 17443962
TI  - Experience pays: offspring survival increases with female age.
AB  - Life-history theory predicts that, in long-lived organisms, effort towards
      reproduction will increase with age, and research from oviparous vertebrates
      largely supports this prediction. In reptiles, where parental care occurs
      primarily via provisioning of the egg, older females tend to produce larger eggs,
      which in turn produce larger hatchlings that have increased survival. We
      conducted an experimental release study and report that maternal age positively
      influences offspring survivorship in the painted turtle (Chrysemys picta) and
      predicts offspring survival at least as well as hatchling body size does. These
      data suggest that, although increasing hatchling size is a major component of
      reproductive success in older individuals, other factors also contribute.

PMID- 17443963
TI  - Reproducing lizards modify sex allocation in response to operational sex ratios.
AB  - Sex-allocation theory suggests that selection may favour maternal skewing of
      offspring sex ratios if the fitness return from producing a son differs from that
      for producing a daughter. The operational sex ratio (OSR) may provide information
      about this potential fitness differential. Previous studies have reached
      conflicting conclusions about whether or not OSR influences sex allocation in
      viviparous lizards. Our experimental trials with oviparous lizards (Amphibolurus
      muricatus) showed that OSR influenced offspring sex ratios, but in a direction
      opposite to that predicted by theory: females kept in male-biased enclosures
      overproduced sons rather than daughters (i.e. overproduced the more abundant
      sex). This response may enhance fitness if local OSRs predict survival
      probabilities of offspring of each sex, rather than the intensity of sexual
      competition.

PMID- 17443964
TI  - The nested structure of marine cleaning symbiosis: is it like flowers and bees?
AB  - In a given area, plant-animal mutualistic interactions form complex networks that
      often display nestedness, a particular type of asymmetry in interactions. Simple
      ecological and evolutionary factors have been hypothesized to lead to nested
      networks. Therefore, nestedness is expected to occur in other types of mutualisms
      as well. We tested the above prediction with the network structure of
      interactions in cleaning symbiosis at three reef assemblages. In this type of
      interaction, shrimps and fishes forage on ectoparasites and injured tissues from
      the body surface of fish species. Cleaning networks show strong patterns of
      nestedness. In fact, after controlling for species richness, cleaning networks
      are even more nested than plant-animal mutualisms. Our results support the notion
      that mutualisms evolve to a predictable community-level structure, be it in
      terrestrial or marine communities.

PMID- 17443965
TI  - 800,000 year old mammoth DNA, modern elephant DNA or PCR artefact?
AB  - Poulakakis and colleagues (Poulakakis et al. 2006: Biol. Lett. 2, 451-454),
      report the recovery of 'authentic' mammoth DNA from an 800,000-year-old fragment
      of bone excavated on the island of Crete. In light of results from other ancient
      DNA studies that indicate how DNA survival is unlikely in samples, which are
      recovered from warm environments and are relatively old (e.g. more than 100,000
      years), these findings come as a great surprise. Here, we show that problems
      exist with the methodological approaches used in the study. First, the nested PCR
      technique as reported is nonsensical--one of the second round 'nested' primers
      falls outside the amplicon of the first round PCR. More worryingly, the binding
      region of one of the first round primers (Elcytb320R) falls within the short 43
      base pair reported mammoth sequence, specifically covering two of the three
      reportedly diagnostic Elephas polymorphisms. Finally, we demonstrate using a
      simple BLAST search in GenBank that the claimed 'uniquely derived character
      state' for mammoths is in fact also found within modern elephants.

PMID- 17443966
TI  - Does the 43 bp sequence from an 800,000 year old cretan dwarf elephantid really
      rewrite the textbook on mammoths?
AB  - Pigmy elephants inhabited the islands from the Mediterranean region during the
      Pleistocene period but became extinct in the course of the Holocene. Despite
      striking distinctive anatomical characteristics related to insularity, some
      similarities with the lineage of extant Asian elephants have suggested that pigmy
      elephants could be most probably seen as members of the genus Elephas. Poulakakis
      et al (2006) have recently challenged this view by recovering a short mtDNA
      sequence from an 800 000 year old fossil of the Cretan pigmy elephant (Elephas
      creticus). According to the authors of this study, a deep taxonomic revision of
      Cretan dwarf elephants would be needed, as the sequence exhibits clear affinities
      with woolly mammoth haplotypes. However, we point here many aspects that
      seriously weaken the strength of the ancient DNA evidence reported.

PMID- 17443967
TI  - Familiarity accentuates gaze cuing in women but not men.
AB  - Gaze cuing, the tendency to shift attention in the direction other individuals
      are looking, is hypothesized to depend on a distinct neural module. One
      expectation of such a module is that information processing should be
      encapsulated within it. Here, we tested whether familiarity, a type of social
      knowledge, penetrates the neural circuits governing gaze cuing. Male and female
      subjects viewed the face of an adult male looking left or right and then pressed
      a keypad to indicate the location of a target appearing randomly left or right.
      Responses were faster for targets congruent with gaze direction. Moreover, gaze
      cuing was stronger in females than males. Contrary to the modularity hypothesis,
      familiarity enhanced gaze cuing, but only in females. Sex differences in the
      effects of familiarity on gaze cuing may reflect greater adaptive significance of
      social information for females than males.

PMID- 17443968
TI  - Differential influence of Pomphorhynchus laevis (Acanthocephala) on brain
      serotonergic activity in two congeneric host species.
AB  - The physiological mechanisms by which parasites with complex life cycles
      manipulate the behaviour of their intermediate hosts are still poorly understood.
      In Burgundy, eastern France, the acanthocephalan parasite Pomphorhynchus laevis
      inverses reaction to light in its amphipod host Gammarus pulex, but not in
      Gammarus roeseli, a recent invasive species. Here, we show that this difference
      in manipulation actually reflects a difference in the ability of the parasite to
      alter brain serotonergic (5-HT) activity of the two host species. Injection of 5
      HT in uninfected individuals of both host species was sufficient to inverse
      reaction to light. However, a difference in brain 5-HT immunocytochemical
      staining levels between infected and uninfected individuals was observed only in
      G. pulex. Local adaptation of the parasite to the local host species might
      explain its inability to manipulate the behaviour and nervous system of the
      invasive species.

PMID- 17443969
TI  - The tail of the Ordovician fish Sacabambaspis.
AB  - The tail of the earliest known articulated fully skeletonized vertebrate, the
      arandaspid Sacabambaspis from the Ordovician of Bolivia, is redescribed on the
      basis of further preparation of the only specimen in which it is most extensively
      preserved. The first, but soon discarded, reconstruction, which assumed the
      presence of a long horizontal notochordal lobe separating equal sized dorsal and
      ventral fin webs, appears to have considerable merit. Although the ventral web is
      significantly smaller than the dorsal one, the presence of a very long
      notochordal lobe bearing a small terminal web is confirmed. The discrepancy in
      the size of the ventral and dorsal webs rather suggests that the tail was
      hypocercal, a condition that would better accord with the caudal morphology of
      the living agnathans and the other jawless stem gnathostomes.

PMID- 17443970
TI  - Feeding mechanics and bite force modelling of the skull of Dunkleosteus terrelli,
      an ancient apex predator.
AB  - Placoderms are a diverse group of armoured fishes that dominated the aquatic
      ecosystems of the Devonian Period, 415-360 million years ago. The bladed jaws of
      predators such as Dunkleosteus suggest that these animals were the first
      vertebrates to use rapid mouth opening and a powerful bite to capture and
      fragment evasive prey items prior to ingestion. Here, we develop a biomechanical
      model of force and motion during feeding in Dunkleosteus terrelli that reveals a
      highly kinetic skull driven by a unique four-bar linkage mechanism. The linkage
      system has a high-speed transmission for jaw opening, producing a rapid expansion
      phase similar to modern fishes that use suction during prey capture. Jaw closing
      muscles power an extraordinarily strong bite, with an estimated maximal bite
      force of over 4400 N at the jaw tip and more than 5300 N at the rear dental
      plates, for a large individual (6 m in total length). This bite force capability
      is the greatest of all living or fossil fishes and is among the most powerful
      bites in animals.

PMID- 17443971
TI  - A two-headed reptile from the Cretaceous of China.
AB  - A malformed embryonic or neonate choristoderan reptile from the Lower Cretaceous
      Yixian Formation of northeastern China is described. The tiny skeleton exhibits
      two heads and two necks, with bifurcation at the level of the pectoral girdle. In
      a fossil, this is the first occurrence of the malformation known as axial
      bifurcation, which is well known in living reptiles.

PMID- 17443972
TI  - Host plant and population determine the fitness costs of resistance to Bacillus
      thuringiensis.
AB  - Novel adaptations often cause pleiotropic reductions in fitness. Under optimal
      conditions individual organisms may be able to compensate for, or reduce, these
      fitness costs. Declining environmental quality may therefore lead to larger
      costs. We investigated whether reduced plant quality would increase the fitness
      costs associated with resistance to Bacillus thuringiensis in two populations of
      the diamondback moth Plutella xylostella. We also measured the rate of decline in
      resistance on two host-plant (Brassica) species for one insect population
      (Karak). Population X plant species interactions determined the fitness costs in
      this study. Poor plant quality increased the fitness costs in terms of
      development time for both populations. However, fitness costs seen in larval
      survival did not always increase as plant quality declined. Both the fitness and
      the stability experiment indicated that fitness costs were higher on the most
      suitable plant for one population. Theoretically, if the fitness cost of a
      mutation interacts additively with environmental factors, the relative fitness of
      resistant insects will decrease with environmental quality. However,
      multiplicative costs do not necessarily increase with declining quality and may
      be harder to detect when fitness parameters are more subject to variation in
      poorer environments.

PMID- 17443973
TI  - Scaling of tree vascular transport systems along gradients of nutrient supply and
      altitude.
AB  - A recent metabolic scaling theory predicts that plants minimize resistance to
      hydraulic conduction in the bulk transport network by narrowing the diameter of
      xylem conduits distally. We hypothesized that trees growing at high altitude or
      on nutrient-depleted soils would prioritize survival over minimizing hydraulic
      resistance, and that their vascular systems would be structured differently from
      those of trees growing under more benign conditions. In fact, conduits were
      observed to narrow towards the periphery of vascular system within all 45 trees
      of three species we investigated, and scaling relationships were
      indistinguishable across a range of environments. Thus, conduit tapering
      relationships appear to be invariant with respect to environmental conditions.

PMID- 17443974
TI  - NSAIDs and scavenging birds: potential impacts beyond Asia's critically
      endangered vultures.
AB  - Veterinary treatment of livestock with diclofenac, a non-steroidal anti
      inflammatory drug (NSAID), has caused catastrophic declines of Gyps vultures in
      Asia. This has highlighted a lack of knowledge on the potential impacts of NSAIDs
      on scavenging birds. Surveys of veterinarians and zoos document the outcomes of
      the treatment of over 870 scavenging birds from 79 species. As well as
      diclofenac, carprofen and flunixin were associated with mortality, with deaths
      observed in 13 and 30% of cases, respectively. Mortality was also found following
      treatment with ibuprofen and phenylbutazone. NSAID toxicity was reported for
      raptors, storks, cranes and owls, suggesting that the potential conservation
      impact of NSAIDs may extend beyond Gyps vultures and could be significant for New
      World vultures. In contrast, there were no reported mortalities for the NSAID
      meloxicam, which was administered to over 700 birds from 60 species. The relative
      safety of meloxicam supports other studies indicating the suitability of this
      NSAID to replace diclofenac in Asia.

PMID- 17443975
TI  - Eat now, pay later? Evidence of deferred food-processing costs in diving seals.
AB  - Seals may delay costly physiological processes (e.g. digestion) that are
      incompatible with the physiological adjustments to diving until after periods of
      active foraging. We present unusual profiles of metabolic rate (MR) in grey seals
      measured during long-term simulation of foraging trips (4-5 days) that provide
      evidence for this. We measured extremely high MRs (up to almost seven times the
      baseline levels) and high heart rates during extended surface intervals, where
      the seals were motionless at the surface. These occurred most often during the
      night and occurred frequently many hours after the end of feeding bouts. The
      duration and amount of oxygen consumed above baseline levels during these events
      was correlated with the amount of food eaten, confirming that these metabolic
      peaks were related to the processing of food eaten during foraging periods
      earlier in the day. We suggest that these periods of high MR represent a payback
      of costs deferred during foraging.

PMID- 17443976
TI  - Changes in body temperature influence the scaling of VO2max and aerobic scope in
      mammals.
AB  - Debate on the mechanism(s) responsible for the scaling of metabolic rate with
      body size in mammals has focused on why the maximum metabolic rate (VO2max )
      appears to scale more steeply with body size than the basal metabolic rate (BMR).
      Consequently, metabolic scope, defined as VO2max/BMR, systematically increases
      with body size. These observations have led some to suggest that VO2max, and BMR
      are controlled by fundamentally different processes, and to discount the
      generality of models that predict a single power-law scaling exponent for the
      size dependence of the metabolic rate. We present a model that predicts a steeper
      size dependence for VO2max than BMR based on the observation that changes in
      muscle temperature from rest to maximal activity are greater in larger mammals.
      Empirical data support the model's prediction. This model thus provides a
      potential theoretical and mechanistic link between BMR and VO2 max.

PMID- 17443977
TI  - TB-infected deer are more closely related than non-infected deer.
AB  - Identifying mechanisms of pathogen transmission is critical to controlling
      disease. Social organization should influence contacts among individuals and thus
      the distribution and spread of disease within a population. Molecular genetic
      markers can be used to elucidate mechanisms of disease transmission in wildlife
      populations without undertaking detailed observational studies to determine
      probable contact rates. Estimates of genealogical relationships within a bovine
      tuberculosis-infected white-tailed deer (Odocoileus virginianus) population
      indicated that infected deer were significantly more closely related than non
      infected deer suggesting that contact within family groups was a significant
      mechanism of disease transmission. Results demonstrate that epidemiological
      models should incorporate aspects of host ecology likely to affect the
      probability of disease transmission.

PMID- 17443978
TI  - Harvesting of males delays female breeding in a socially monogamous mammal; the
      beaver.
AB  - Human exploitation may skew adult sex ratios in vertebrate populations to the
      extent that males become limiting for normal reproduction. In polygynous
      ungulates, females delay breeding in heavily harvested populations, but effects
      are often fairly small. We would expect a stronger effect of male harvesting in
      species with a monogamous mating system, but no such study has been performed. We
      analysed the effect of harvesting males on the timing of reproduction in the
      obligate monogamous beaver (Castor fiber). We found a negative impact of
      harvesting of adult males on the timing of parturition in female beavers. The
      proportion of normal breeders sank from over 80%, when no males had been shot in
      the territories of pregnant females, to under 20%, when three males had been
      shot. Harvesting of males in monogamous mammals can apparently affect their
      normal reproductive cycle.

PMID- 17443979
TI  - Positive short-term effects of sheep grazing on the alpine avifauna.
AB  - Grazing by large herbivores may negatively affect bird populations. This is of
      great conservation concern in areas with intensive sheep grazing. Sheep
      management varies substantially between regions, but no study has been performed
      in less intensively grazed systems. In a fully replicated, landscape scale
      experiment with three levels of sheep grazing, we tested whether the abundance
      and diversity of an assemblage of mountain birds were negatively affected by
      grazing or if grazing facilitated the bird assemblage. Density of birds was
      higher at high sheep density compared with low sheep density or no sheep by the
      fourth grazing season, while there was no clear effect on bird diversity. Thus,
      agricultural traditions and land use politics determining sheep density may
      change the density of avifauna in either positive or negative directions.

PMID- 17443980
TI  - Do probiotics prevent allergy?

PMID- 17443982
TI  - Medication. Why it's important to "use as directed".

PMID- 17443981
TI  - Child development. Back-to-sleep--and how to reduce the likelihood of flat heads.

PMID- 17443983
TI  - Diet & nutrition. Good news: caffeine in pregnancy doesn't affect the baby's
      growth...and folic acid seems to prevent cleft lip.

PMID- 17443984
TI  - Product recalls. Recalls: children's hooded sweatshirts with drawstrings...and
      Kids II teethers.

PMID- 17443986
TI  - When children assault children.

PMID- 17443985
TI  - Dependent personality disorder. Threatened by self-reliance, they take shelter in
      submission.

PMID- 17443987
TI  - Efficacious, yet ineffective.

PMID- 17443988
TI  - Depression at menopause.

PMID- 17443989
TI  - Schizophrenia and physical illness.

PMID- 17443990
TI  - Questions & answers. Is there an effective treatment for hair pulling
      (trichotillomania)?

PMID- 17443991
TI  - Stent safety questioned.

PMID- 17443992
TI  - Don't underestimate anemia.

PMID- 17443993
TI  - Unraveling the mystery of frailty.

PMID- 17443994
TI  - What's so special about statins?

PMID- 17443995
TI  - Can lung cancer screening save lives?

PMID- 17443996
TI  - What, other than drinking water, can help flush out a kidney stone?

PMID- 17443997
TI  - Use of zirconia in restorative dentistry.

PMID- 17443998
TI  - Is solar UV frying fish?

PMID- 17443999
TI  - Crossing the scales. Interview by Rebecca Gillan.

PMID- 17444000
TI  - Living computers.

PMID- 17444002
TI  - Dr. Richard Ellen: An inside view of oral health research in Canada. Interview by
      Sean McNamara.

PMID- 17444001
TI  - Oral health-systemic health: what is the true connection? Interviews by Sean
      McNamara.

PMID- 17444003
TI  - Oral health researcher: a viable career option.

PMID- 17444004
TI  - [Abstracts of the 30th Scientific Congress of the German League against High
      Blood Pressure and the German Society of Hypertension, November 22-24, 2006,
      Munich].

PMID- 17444005
TI  - [Abstracts of the Annual Meeting of the Ophthalmologists Society of Saxony in
      conjunction with the Dresden Glaucoma Meeting, December 8-10, 2006, Dresden,
      Germany].

PMID- 17444007
TI  - Abstracts of the XVIIth European Meeting of the French Society of Cardiology, 17
      20 January 2007, Paris, France.

PMID- 17444006
TI  - Abstracts of the 51st Annual Meeting of the German Society of Endocrinology
      together with the 12th Annual Meeting of the Austrian Society of Endocrinology
      and Metabolism, March 7-10, 2007, Salzburg.

PMID- 17444008
TI  - [Abstracts of the 31st Francophone Meeting of Digestive Pathology, 17-21 March
      2007, Lyon, France].

PMID- 17444009
TI  - CDC's call for routine HIV testing raises implementation concerns.

PMID- 17444010
TI  - Abstracts of the 80th Annual Meeting of the Japanese Pharmacological Society,
      March 14-16, 2007, Nagoya, Japan.

PMID- 17444011
TI  - A systematic future? Interview by Katherine Vickers.

PMID- 17444012
TI  - The soft cell.

PMID- 17444013
TI  - [Proceedings and abstracts of the XXI Annual Meeting of Applied Research in
      Chagas Disease and Leishmaniasis, Uberaba, Brazil, 21-23 October 2005].

PMID- 17444014
TI  - Abstracts of the 16th International Congress of Cytology, May 13-17, 2007,
      Vancouver, Canada.

PMID- 17444015
TI  - A special issue on application od signal detection theory to visual perception.

PMID- 17444016
TI  - [Abstracts of the Congress of Urology of the French-speaking Languages and the
      7th National Congress of Urology, 8-10 February 2007, Tunis, Tunisia].

PMID- 17444017
TI  - [Thoughts on "defensive" medicine].
AB  - "Defensive" medicine is called medical behaviour characterized by deformation of
      diagnostic and therapeutic activities due to fears endangering existence and
      work, thus some interventions are omitted or, on the contrary, superfluous
      examinations are proposed on account of internal uncertainty, the patient's
      distrust or hostile social environment. Trust relation between patient and
      physician is the most gravely damaged because of aggravation and distortion of
      some conscienceless physicians' abuses by the media; patient-physician relations
      may not be degraded to contractual legal relations. Young physicians must get
      acquainted with the joy of success in diagnostics that enriches the personality.
      They shall have healthy self-esteem and be ready to take diagnostic and
      therapeutic challenges on themselves. All of us have to fight against social
      atmosphere hostile to physicians, against causes inducing and augmenting practice
      of defensive medicine.

PMID- 17444018
TI  - [The state of organized cervical screening program in Hungary in 2006].
AB  - Theoretically, there is a real prospect for full eradication of cervical cancer
      by cytology screening. In several countries the burden of cervical cancer
      significantly decreased due to regular screening of the population. In Hungary,
      the complex "gynecological screening", including colposcopic examination, has a
      long tradition, however, the efforts of several decades are not reflected in the
      mortality: about 500 women are killed by cervical cancer each year. The screening
      protocol represents a compromise between the traditional "gynecological
      screening" and the internationally recommended organized screening: taking sample
      for cytology is an essential element of the gynecological examination. The
      National Public Health Programme has established the technical and organizational
      preconditions of an organized screening programme. The early experiences with the
      "call-and-recall" organized screening -- started at the end of 2003 -- are
      unfavourable, because the compliance rates are unacceptably low. The majority of
      the women receive screening in a traditional way, i.e. outside the programme;
      another proportion of them simply ignores the invitation, and does not accept the
      offered screening. To improve the current situation, following the recommendation
      of "the-state-of-the-art", an attempt is made to intensify the involvement of the
      primary care personnel. There is a need to revise the current financing system by
      the political decision-makers in the health field. The access to the screening
      facilities needs to be improved, the attitude of the medical community changed,
      and the efficiency of the communication with the public significantly improved.

PMID- 17444019
TI  - [Supraventricular ectopy with unaltered sinus rhythm].

PMID- 17444020
TI  - [Clinical pharmacological aspects of the proton pump inhibitor therapy:
      importance of pharmacogenetic differences in the clinical practice].
AB  - Proton pump inhibitors (PPIs) are widely used for the treatment of
      gastroesophageal reflux disease, as well as other acid-related disorders.
      Omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole effectively
      suppress gastric acid secretion by blocking the gastric acid pump, H+/K+ 
      adenosine triphosphatase (ATPase). Understanding the pharmacokinetic properties
      of PPIs and examining the pharmacogenetic differences may help clinicians to
      optimize PPI therapy and to perform individual treatment, especially in non
      responder patients with GERD or ulcer or after failed eradication therapy.

PMID- 17444021
TI  - [HLA class I antibody screening and typing in the sera of dialyzed patients with
      CDC and ELISA techniques: association with graft survival].
AB  - AIM: As generally accepted, HLA antibody screening and typing in dialyzed kidney
      patients are important for the successful outcome of transplantation. METHOD:
      Authors investigated the serum samples of 133 patients from the north-eastern
      region of Hungary for HLA class I antibodies with complement dependent
      cytotoxicity(CDC) and solid phase enzyme linked immunosorbent (ELISA) techniques
      (Biotest Abscreen and Abident class I), respectively. RESULTS: The comparison of
      the results revealed a strong correlation (c2=7,23, p < 0,01) for antibody
      screening. However, the two methods detect two slightly different antibody
      populations. The deviation is mainly to be attributed to the higher sensitivity
      of ELISA, which resulted in antibody positivity of some CDC negative sera (25/106
      23,6%), despite the fact that ELISA detects IgG alone. The authors investigated
      56 patients, who had already undergone transplantation but got back on the
      waiting list later and found that average graft survival was shorter in the group
      of patients with antibody, regardless to the method applied. However, the
      difference in graft survival proved to be more significant if the patients were
      assorted to groups by ELISA rather than CDC positivity (ELISA: 58,4 vs 111,2
      months - p < 0,001, CDC:50,5 vs 75,6 months - p > 0,05, n.s.). CONCLUSION: This
      observation suggests that the clinical relevance of antibodies detected by ELISA
      alone -- due to its higher sensitivity -- are not to be ignored. In this context
      authors emphasize the HLA class I antibody screening and typing in the post
      transplantation period.

PMID- 17444022
TI  - [Cooperation or false authorship? Scientometric investigations on the connections
      between the number of authors, the scientific cooperation and the effectivity].
AB  - INTRODUCTION: The non-genuine authorship can influence reality of scientometric
      evaluations. At the same time, cooperation among scientists and institutes is an
      intrinsic factor of science, which heightens the level of scientific effectivity.
      The differentiation of these phenomenons is extremely important in Hungary, where
      the support of the scientific research is often escorted by and depends on
      scientometric evaluations. AIMS: The authors intended to establish a method aimed
      at the bibliometric validation of the hypothesis: there exists a positive
      connection between cooperation and the niveau of scientific publications.
      MATERIALS AND METHODS: The scientific articles of the researchers of the Medical
      Faculty of the Szeged University, published in journals having impact factor,
      were divided into clinical and theoretical articles. These groups were divided
      further on the basis that the researchers of the "owner" Medical Faculty
      institutes were in majority or minority among the authors. The member articles of
      the groups were ranked according to the impact factors, then the author number
      means of the higher and the lower half were compared. RESULTS: The higher is the
      number of authors, the higher is the impact factor of the journal article
      publications, i.e. the cooperation between authors as well as institutes
      heightens the niveau of the publications.

PMID- 17444023
TI  - [Letter to the Editor of Kardiologia Polska - Professor Piotr Kulakowski].

PMID- 17444024
TI  - [Apical ballooning syndrome - terminology for translating].

PMID- 17444025
TI  - Inconsistent government policies: why FDA off-label regulation cannot survive
      First Amendment review under Greater New Orleans.

PMID- 17444026
TI  - Issues in the interpretation of 180-day exclusivity.

PMID- 17444027
TI  - Potential pathways for abbreviated approval of generic biologics under existing
      law and proposed reforms to the law.

PMID- 17444028
TI  - State laws on school vending: the need for a public health approach.

PMID- 17444029
TI  - A free market for dietary supplements: issues surrounding DSHEA's exceptions to
      the labeling exemption for third-party literature.

PMID- 17444030
TI  - Reading our lips: the history of lipstick regulation in Western seats of power.

PMID- 17444031
TI  - FDA's regulation of prescription drug labeling: a role for implied preemption.

PMID- 17444032
TI  - Branded drug reformulation: the next brand vs. generic antitrust battleground.

PMID- 17444033
TI  - [Progress of standardizations for clinical visual electrophysiology].
AB  - To meet the needs for standardizations of clinical visual electrophysiology, the
      International Society for Clinical Electrophysiology of Vision (ISCEV) has issued
      serial proposals of standards since the last decade of the 20th century. The
      present state of standardization in the laboratories of our country has been
      improved, but it needs more efforts to meet the latest requirements. This article
      reviewed the main contents of these standards.

PMID- 17444034
TI  - [Progress of aspheric intraocular lens].
AB  - Aspheric intraocular lens is a new intraocular lens that was a recent focus
      clinically. It can lessen aberration, improve cataract patients' quality of
      postoperative vision, better satisfy their demand for higher vision when
      comparing with traditional intraocular lens. Therefore, aspheric intraocular lens
      is becoming the main guide of future intraocular lens. The purpose of this review
      is to summarize its design features , principle , classification, clinical
      application and functional assessment.

PMID- 17444035
TI  - [Thioltransferase and thioredoxin system in cataract].
AB  - The lens depends on a balanced redox state and SH/-S-S- ratio for maintaining its
      transparency. The endogenous high level of glutathione (GSH) and its intrinsic
      repair enzymes are very important lines of defense for the health of the lens.
      However, ageing lenses or cataract lenses show an extensively diminished size of
      GSH pool. The research in thioltransferase (TTase) and thioredoxin (Trx) system
      show TTase can specifically dithiolate protein-S-S-glutathione and restore
      protein free SH groups for proper enzymatic or protein functions; Trx system can
      dithiolate protein disulfides and thus is an extremely important regulator for
      redox homeostasis in the cells. The two enzymes may work synergistically to
      repair thiols in lens proteins and enzymes and maintain the function of the lens
      effectively.

PMID- 17444036
TI  - [Blood vessel multiply and significance of expression of Cox-2, VEGF in
      pterygium].
AB  - OBJECTIVE: To investigate the role of cyclooxygenases-2 (Cox-2) and vascular
      endothelial growth factor (VEGF) in the occurrence and development of human
      pterygium. METHODS: The immunohistochemical elivision method was used to examine
      the expressions of Cox-2 and VEGF in 30 cases of pterygium and 15 cases with
      normal conjunctiva. RESULTS: The positive rate of Cox-2 was 42.8% in resting
      stage, 84.6% in active stage, 90.0% in recurrent pterygium and 6.6% in normal
      conjunctiva. The positive rate of VEGF was 57.1% in resting stage, 69.2% in
      active stage, 100.0% in recurrent pterygium and 13.3% in the normal conjunctiva.
      There was significant difference in the expressions of Cox-2 and VEGF between the
      pterygium and normal conjunctiva (P < 0.05, P < 0.001). CONCLUSIONS: There are
      high Cox-2 and VEGF expressions in pterygium, which suggests that there is
      abnormal blood vessel multiply in pterygium, and the Cox-2 and VEGF plays an
      important role in the incidence and development of pterygium. Specific Cox-2 and
      VEGF inhibitor become a new target for the therapy of pterygium. Specific Cox-2
      and VEGF inhibitor become a new target for the therapy of pterygium.

PMID- 17444037
TI  - [Effects of yiqimingmu solution on models of light damage in rat retina].
AB  - PURPOSE: To investigate the experimental therapeutic effects of Chinese medicine
      Yiqimingmu solution on rats of retina injury models induced by light. METHODS:
      Fifty-four Sprague-Dawley rats were randomly divided into negative control group,
      light damage model group and Yiqimingmu solution group. The light damage model
      was induced by exposing the SD rats' light eyes to the light of green fluorescent
      (intensity = 1900 +/- 106.9 Lux) for 24 hours. Distilled water and Yiqimingmu
      solution were respectively irrigated into rats for 7 days before light expose. In
      6 days after light expose, the change of electroretinogram (ERG) was observed.
      The content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD)
      in rats retina were measured, and the histopathologic changes were observed with
      transmission electron microscopy and light microscopy. RESULTS: In 6 days after
      light expose, Yiqimingmu solution had protective effects on fall of ERG a wave
      and b wave amplitude induced by light damage. The activity of SOD in Yiqimingmu
      solution group was higher than in light damage model group (P < 0.01= , the
      content of MDA in Yiqimingmu solution group was lower than in light damage model
      group (P < 0.01). The histopathologic injury of rat retina in Yiqimingmu solution
      group was less than in light damage model group by means of transmission electron
      microscopy and light microscopy. CONCLUSIONS: Yiqimingmu solution is an effective
      traditional Chinese medicine to treat diseases of retina light damage.

PMID- 17444038
TI  - In vitro study on lethal effect of human choroidal melanoma OCM-1 cell line by
      repeating -70 degrees C freeze thawing.
AB  - OBJECTIVE: To investigate the effects of repeating -70 degrees C freeze thawing
      on human choroidal melanoma cell line OCM-1. METHODS: OCM-1 cells were frozen by
      repeating -70 degrees C freeze thawing with various durations and frequencies.
      Then the inhibit rate of cells was examined by MTT essay. The cell viability was
      measured by monoclonal formation assay. We also used the HE staining,
      immunohistochemistry staining and the laser-scanning confocal microscopy (LSCM)
      to investigate the morphological changes of the cells. RESULTS: The growth of OCM
      1 cells was inhibited by repeating -70 degrees C freeze thawing in time-dependent
      and frequency-dependent manners (P < 0.01). Different morphous including necrosis
      and apoptosis of the cells could be observed after -70 degrees C freeze thawing
      by the LSCM. CONCLUSION: Repeating -70 degrees C freeze thawing can not only kill
      cells directly and induce considerable cells to apoptosis, but also inhibit the
      growth of the survivals. The kill and wound ratio of the cells disposal with
      different times and frequencies present variance. And the distinction when
      treated with different frequencies during the same time is much more significant
      than different times with the same frequency, which guide clinical workers to
      choose repeating cryotherapy with short term method instead of single cryotherapy
      with long term in choroidal melanoma treatment.

PMID- 17444039
TI  - [Experimental study of the healing condition of sclerotomy sites after 25-gauge
      transconjunctival sutureless sclerotomy and 20-gauge vitrectomy].
AB  - PURPOSE: To compare the healing condition of sclerotomy sites after 25-gauge
      transconjunctival sutureless sclerotomy and conventional 20-gauge vitrectomy in
      minipigs. METHODS: Four minipigs qualified for experiment were included in the
      study. One eye underwent sclerotomy with 25G trocar (25G group) and the other
      underwent 20G-PPV (20G group). The healing processes of sclerotomy sites were
      observed grossly and by Hematoxylin-Eosin (HE) staining under light microscopy at
      0, 10, 20 and 60 days after operation. RESULTS: Compared with 20G group, scleral
      incisions in 25G group were much smaller. One day after operation, conjunctival
      hyperemia in 20G group was more severe than that in 25G group. Sclerotomy sites
      in 25G group mostly healed 10 days after operation with a few inflammation cells.
      Sclerotomy sites in 20G group bad not healed 20 days after operation and were
      infiltrated by a great number of inflammation cells. One case in 25-gauge group
      and 2 cases in 20-gauge group had vitreous incarceration. Two cases in 25-gauge
      group and 4 cases in 20-gauge group had fibrous ingrowth. CONCLUSION: Compared
      with 20-gauge vitrectomy, the smaller sclerotomy sites in 25-gauge
      transconjunctival sutureless sclerotomy heal faster and have lighter inflammation
      reaction. Vitreous incarceration and proliferation ingrowth could be found in
      both surgeries.

PMID- 17444040
TI  - [The clinical investigation of early visual function in cataract patients after
      implantation with aspheric intraocular lens].
AB  - PURPOSE: To initially evaluate the early visual function after implantation with
      aspheric intraocular lens METHODS: Eighty-eight subjects (91 eyes) were divided
      randomly into three groups: AcrySof IQ (SN60WF) group, KS-3Ai group and AcrySof
      Natural (SN60AT) group. Best corrected visual acuity was observed 1 day, 1 week
      and 1 month postoperatively, while contrast sensitivity and subjective vision
      were observed 1 month later. RESULTS: Best corrected visual acuity was obviously
      better in KS-3Ai group than in the other groups 1 day postoperatively (P < 0.05),
      but no significant difference was found 1 week and 1 month later among the groups
      (P > 0.05). When the pupil diameter was in 2.5 to 4.0 mm and 5.0 to 6.0 mm,
      AcrySof IQ and KS-3Ai groups were better than the AcrySof Natural group in the
      low and middle spatial frequency (P < 0.05). However, there was no significant
      difference between AcrySof IQ and KS-3Ai groups (P > 0.05). VF/QOL questionnaire
      was obtained, showing that implantation with AcrySof IQ and KS-3Ai satisfied
      patients preferably. CONCLUSIONS: Aspheric intraocular lens can greatly improve
      patients' contrast sensitivity and quality of vision.

PMID- 17444041
TI  - [Clinical study of pars plana vitrectomy with silicone oil endotamponade in
      posttraumatic endophthalmitis on eyes without retinal detachment].
AB  - PURPOSE: To assess the clinical effect of pars plana vitrectomy (PPV) with
      intravitreous antibiotic drugs or silicone oil endotamponade in post-traumatic
      endophthalmitis on eyes without detachment of the retina. METHODS: Thirty cases
      of eyes with penetrating injury associated with endophthalmitis without retina
      detachment had been treated with PPV plus intravitreous antibiotic drugs or
      silicone oil tamponade. All the patients in the study received intravenous,
      subconjunctival and topical medications antibiotics. RESULTS: All the patients
      were followed up for 3 to 12 months. Postoperative intraocular infection of 30
      eyes (30 patients) were controlled. The best-corrected visual acuity was
      significantly improved in both groups postoperatively (P < 0.05). The rate of
      postoperative retinal detachment in the PPV combined with intravitreal
      antibiotics group was 21.1% (4/19) vs. 9% (1/11)in the PPV combined with silicone
      oil There was no significant difference in postoperative endotamponade group.
      There was no significant difference in postoperative complications between two
      groups. CONCLUSIONS: PPV combined with silicone oil tamponade may have beneficial
      effect on the surgical treatment of traumatic bacterial endophthalmitis
      associated without retinal detachment, but the surgery may be used in some cases
      which have bad retinal condition or uncontrollable inflammation.

PMID- 17444042
TI  - [New agreement in assessing vertical cup: disc ratio using a 78D lens with slit
      lamp eyepiece measuring graticule].
AB  - AIM: To determine the inter-observer agreement in assessing vertical cup: disc
      ratio (VCDR) by using 78D lens with slit-lamp eyepiece measuring graticule (SLMP)
      and direct ophthalmoscope with standard photo (DOSP). METHODS: Four hundred and
      seventy-seven eyes of 257 subjects form one random selected community districts
      were examined. Two observers performed clinical estimations of VCDR. The cup to
      disc ratio (CDR) was assessed by slit-lamp biomicroscopy using a 78D lens and
      measuring eyepiece graticule (SLMP) and also by direct ophthalmoscope with
      standard photo (DOSP). RESULTS: The 95% limits of agreement on VCDR between
      observers was -2.2 to approximately +2.8 for SLMG, and -3.3 to approximately +3.8
      for DOSP. DOSP method consistently overestimates the VCDR compared with the SLMG.
      The inter-observer agreements on disc and cup diameter estimation using SLMP were
      -4.3 to approximately +4.5, -7.2 to approximately +6.2 units respectively. The
      bias was not proportional to VCDR level. CONCLUSION: 78D lens with slit-lamp
      eyepiece measuring graticule has a smaller inter-observer variability compared
      with direct ophthalmoscope with standard photo. This method is a more repeatable
      and cost-effective method of optic disc estimation in clinical and screening
      assessment.

PMID- 17444043
TI  - Features associated with recurrence of idiopathic orbital inflammatory
      pseudotumor.
AB  - PURPOSE: To explore factors which lead to recurrence of idiopathic orbital
      inflammatory pseudotumor (IOIP). METHODS: Idiopathic orbital inflammatory
      pseudotumor in 209 cases between Jan 1, 1978 and Dec 31, 1999 in our hospital was
      evaluated retrospectively. The comparison of clinical and pathological parameters
      between patients with at least one episode of recurrence and those with no
      recurrence at all was performed and analyzed using logistic regression method.
      RESULTS: Follow-up results (with a mean follow-up time of 3.4 years, ranging from
      0.5 year to 21.0 years) showed that the recurrence rate of IOIP was 41%. Sex and
      proptosis were associated with the recurrence of IOIP. Male gender was more
      likely to relapse than female counterparts, with the male being 52% and female
      being 25%. The severer the proptosis is, the higher the rate of recurrence. Among
      the clinical subtypes of IOIP, the rate of recurrence (17%) in cases with
      dacryoadenitis was the lowest, followed by anterior local orbital mass (44%),
      posterior orbital mass (54%), myositis (75%) and diffuse subtype (100%). However,
      the clinical subtypes did not show significant relationship with the recurrence
      of IOIP. CONCLUSIONS: Male gender and severe proptosis are associated with a
      higher recurrent rate in patients with IOIP.

PMID- 17444044
TI  - Unlocking minds.

PMID- 17444045
TI  - Beyond stones & bones.

PMID- 17444046
TI  - Filling up with less.

PMID- 17444047
TI  - Public health law.

PMID- 17444048
TI  - Introducing intradermal rabies vaccination in India: paradigm shift for the
      better.

PMID- 17444049
TI  - An epidemiological study of health and nutritional status of under five children
      in semi-urban community of Gujarat.
AB  - In developing countries, children of 0-5 years of age form a large as well as
      "high risk" group. Malnutrition poses a grave risk to the health of these
      children. The main objectives of this study were to assess the health &
      nutritional status of children of 0-5 years of age group & to study the influence
      of various epidemiological factors on health & nutritional status of children on
      0-5 years of age group. It is a community based cross sectional study done in
      randomly selected three wards of Petlad town, district Anand in Gujarat state.
      300 children of age group 0-5 years selected by systematic sampling method.
      Mother of each child included in the study was subjected to personal interview in
      her own house followed by clinical examination & anthropometric measurements of
      the child. The three indices of nutritional status namely, weight for age, height
      for age, & weight for height were expressed in standard deviation units from the
      median for the international reference populations as per WHONCHS standards &
      were compared with WHONCHS growth reference data. The prevalence of under weight
      (wt. for age below 2SD) was 43.67%. 50.3% children were found stunted (ht. 1br
      age below -2 SID) with higher prevalence in 2nd and 5th year of life. Prevalence
      of wasting (wt. for ht. below 2SD) was comparatively low (23.2% with a peak in
      3rd year of life). These nutritional parameters showed a significant association
      with parental education, socio-economic status, family size, environmental
      conditions (safe drink water, sanitary waste disposal & overcrowding), & episodes
      of common diseases.

PMID- 17444050
TI  - Birth weight pattern in the only referral teaching hospital in Manipur.
AB  - Birth weight is an important determinant for child development and survival.
      Birth weight has been reported to be increasing with the passing years. There is
      no such accurate documentation from the state of Manipur. This cross sectional
      study has been attempted to see the birth weight pattern in the largest referral
      hospital in Manipur. Birth weights of four reference years in the last 15 years
      have been extracted from the records and analysed. There were 19478 singleton
      deliveries in the four reference years. The mean birth weight showed a gradual
      increase in these years. There was a gain of 88.9 g in 2000 since 1986 in term
      deliveries. There were significant differences in the mean birth weights among
      the four years, even after stratifying for gestation. However, there was no
      significant decrease in the percentage of low birth weight babies in these years.
      Low birth weight showed significant association with parity, age of the mother,
      booking status, haemoglobin level, and literacy of the mother. Since there was no
      significant decrease in low birth weight babies in spite of increasing birth
      weight, there is a need for continued and committed effort to realize the goals
      of RCH.

PMID- 17444051
TI  - A pilot survey on hand washing among some communities of West Bengal.
AB  - A cross-sectional observational study was carried out between April to May 2006
      by interview method and observation technique with the objective to know the
      knowledge regarding hand washing in the community and it was done in the slum and
      nonslum urban areas and also one rural area. The result shows that in urban slum
      area 98% washed their hands with soap after defecation; Only 36%, 16% and 2%
      washed their hands with soap before meal, before serving food and before cooking
      respectively. However, it was observed that 69% used soap and water for hand
      washing after cleaning the child's faeces. In rural area 71% used soap and water
      after defecation while 26% used mud or ash. Only 13%, 1%, 1% and 5% used soap and
      water before meal, before serving food, before cooking and after cleaning the
      child's faeces. 82.35% of respondents in non slum area and 89% of respondents in
      rural area considered that diarrhoea and dysentery could be prevented by hand
      washing while they did not give importance to hand washing in prevention of
      diarrhoea over other methods like cleanliness, boiling and purification of water.
      ARI was much higher (25.72%) in rural area followed by slum area (13.77%) and non
      slum area (3.87%). Out of 30 observations among 302 interview made on hand
      washing only first step i.e. palm washing (transient rubbing the palm with soap)
      was followed by all the participants observed. Time taken for such hand-washing
      was only around five seconds (ideal 15-30 seconds) in urban slum and rural areas
      while in non slum area it varied between 7-10 seconds on an average. No one
      followed any other steps of hand-washing, recommended by IFH.

PMID- 17444052
TI  - Absorption of nicotine induces oxidative stress among bidi workers.
AB  - Chronic exposure to tobacco dust causes nasal inhalation and cutaneous absorption
      of tobacco alkaloids especially nicotine, therefore the considerable evidences
      showed that workers employed in bidi industries are at risk of cancer, lung
      diseases and other many health related common problems. Many references revealed
      that tobacco dust exposure induces mutations, damage to DNA etc. which are
      supposed to be the consequences of free radical generation. In present study
      attempt have been made to evaluate the status of oxidants and antioxidants and
      their relation with nicotine. 90 bidi workers were screened for serum lipid
      peroxide (MDA) and serum nitric oxide (NO*) as oxidant and erythrocytic
      Superoxide Dismutase (RBC-SOD), Vitamin-C as antioxidant. Total antioxidant
      capacity (TAC) and urinary cotinine were also measured. These bidi workers were
      further divided in 3 groups, Group 1, 11 and III exposed to tobacco dust for
      about 10 to 14 yrs, 15 to 19 yrs and 20 to 24 yrs of exposure respectively.
      Highly significant excretion of Urinary cotinine was found in all groups of bidi
      workers as compared with control (p < 0.001). The levels of MDA, and NO* were
      found to be significantly elevated in all the three groups with progression of
      exposure, than the control (p < 0.001), where as the levels of RBC-SOD, Vitamin-C
      and TAC were significantly decreased in all the three groups as compared with
      controls (p < 0.001). From our findings it is evident that nicotine absorption
      might contribute to the disturbed oxidant and antioxidant balance leading to
      oxidative stress.

PMID- 17444053
TI  - Cases referred for tests of thyroid function disorders at a tertiary care
      teaching hospital of Bihar: some experience.
AB  - In the absence of valid hospital protocol for clinical departments of M.G.M.
      Medical College and L.S.K.Hospital, Kishanganj, as many as, 76.78% of patients
      was referred to biochemistry laboratory, in which disease was not present. Of 196
      diseased (23.22% of total), male and female was respectively 44 and 152. There
      was no significant sex difference in positivity among patients referred for
      investigation. Hypothyroid was major diagnosis, yet hyperthyroid was noticeable.

PMID- 17444054
TI  - Retrospective study of lymphadenopathy by FNAC in a tertiary hospital in North
      East India.

PMID- 17444055
TI  - Knowledge and food hygiene practices among food handlers employed in food
      establishments of Bijapur City.

PMID- 17444056
TI  - Morbidity and treatment seeking behavior among adolescent girls in a rural area
      of North 24 Parganas district, West Bengal.
AB  - A community based, cross-sectional study, conducted in 1999 in a rural area of
      West Bengal, among 143 adolescent girls (10-19 years), selected through
      multistage sampling procedure revealed prevalence of acute and chronic morbidity
      as 30.8% and 7.7% respectively. 84.1% adolescent girls sought for treatment
      during acute morbidity from various sources; only 22.7% from Government health
      facilities. Non- availability of medicine (34%), long distance (24%) and poor
      quality of treatment (10%) were the main reasons for non-utilization of
      Government health facilities.

PMID- 17444057
TI  - TB and DOTS: a human rights perspective.
AB  - Health and human rights are inextricably linked. Factors that violate human
      rights are likely to result in deprivation and ill-health. TB leads to disability
      and death thus negatively impacting human rights, more so in poor and
      marginalised groups. On the other hand DOTS strategy as exemplified by India's TB
      control programme serves to protect human rights by increasing political
      commitment, equitable access to quality services and enhancing accountability. By
      adequate treatment and cure of TB patient, it not only serves the individual but
      also community by preventing spread and emergence of resistance to available
      drugs.

PMID- 17444058
TI  - Smoke free work place an institute of Swasthya (an NGO for tobacco-free, healthy
      life).

PMID- 17444059
TI  - Chikungunya virus returns to Indian Ocean.

PMID- 17444060
TI  - A study of sleeping disorders in blind patients.
AB  - An internal 24-hour biological clock working in tandem with external
      environmental cues like bright light regulates our daily rhythms specially sleep
      wake cycle. In a blind individual, due to absence of external cue endogenous
      rhythm may take upper hand and free running of sleep-wake cycle starts without
      any synchronicity with day-night cycle, creating ground for sleep disorders. To
      evaluate the frequency of sleep disorders, 65 blind individuals without any
      comorbid medical or surgical problem were interviewed according to the criteria
      of Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV).
      Simultaneously 70 persons with no visual impairment were assessed in the same
      manner as used for blind persons. Blind patients showed far higher presence
      (44.6%) of sleep problems compared to controls (15.7%), and this difference was
      highly significant statistically [odd's ratio (OR) = 4.32, CI 95 =1.8-10.54].
      Blind patients showed far higher presence (43.1%) of DSM-IV based diagnosis
      compared to controls (8.6%), and this difference was highly significant
      statistically [OR = 8.072, CI 95 = 3.059-21.298]. Circadian sleep disorders,
      insomnia and hypersomnia were relatively higher in blind patients. High incidence
      of sleep disorders calls for development of short reliable screener for sleep
      disorders among blind persons and better liaison among ophthalmologists and
      psychiatrists for early detection of this problem.

PMID- 17444061
TI  - A study on dyslipidaemia in subclinical hypothyroidism.
AB  - Subclinical hypothyroidism is characterised by elevated serum thyroid stimulating
      hormone (TSH) concentrations in association with normal free thyroid hormones.
      The aim of the study was to evaluate the prevalence and pattern of serum lipid
      alterations in patients with stable subclinical hypothyroidism in comparison to
      age- as well as sex-matched euthyroid group and also subgroup analysis between
      them in regard to age of presentation, sex, antithyroperoxidase (anti TPO)
      positivity, and TSH value. In this study, 100 patients of SCH were recruited, age
      ranged 17-68 years, majority (78%) being females, presenting mainly with non
      specific symptoms and compared with 52 euthyroid control regarding lipid
      parameters. Of the subclinical hypothyroidism patients, only 10% had goitre and
      anti TPO was positive in 52% cases. Serum lipoprotein (a) above the age of 20
      years, and total cholesterol, triglyceride and low density liporpotein
      cholesterol in the age group of 40-50 years were significantly elevated. In
      addition, total cholesterol, triglyceride and low density lipoprotein cholesterol
      levels in anti TPO positive cases and serum triglyceride and low density
      lipoprotein cholesterol in anti TPO negative patients showed statistically
      significant higher levels. In males only lipoprotein (a), but in females total
      cholesterol, triglyceride, low density lipoprotein cholesterol and liproprotein
      (a)--all were significantly elevated.

PMID- 17444062
TI  - Correlation of endometrial ultrasonography and endometrial histopathology in
      patients with postmenopausal bleeding.
AB  - A retrospective study of 49 cases with persistent postmenopausal vaginal bleeding
      undergoing hysterectomy in the absence of postoperatively evident diagnosis of
      genital malignancy was carried out. Normal endometrium was the source of bleeding
      in 24 cases (48.9%) while 11 cases (22.4%) had evidence of endometritis.
      Endometrial hyperplasia and polyps were present in 12 cases (24.4%). Two cases
      were found to have malignancy in the surgical specimen, which were not evident on
      pre-operative endometrial biopsy. However, there was high degree of suspicion of
      malignancy in these 2 cases based on the endometrial histopathology and
      ultrasonographic endometrial thickness. By careful correlation of clinical
      findings, endometrial histopathology and ultrasound measurement of endometrial
      thickness, most cases with postmenopausal bleeding can be managed conservatively.

PMID- 17444063
TI  - Diagnosis and management of metabolic alkalosis.
AB  - Elevated pH and elevated plasma bicarbonate level above normal characterise
      metabolic alkalosis. When bicarbonate is elevated pCO2 must also be elevated to
      maintain pH to its normal range. Therefore with metabolic alkalosis, the
      compensation is to decrease alveolar ventilation, and increase pCO2. The causes
      of metabolic alkalosis are gastro-intestinal hydrogen and chloride loss and due
      to renal cause. For metabolic alkalosis to continue both generation and
      maintenance of high levels of bicarbonate are necessary. The diagnosis of
      metabolic alkalosis is established by noting pH, serum bicarbonate (elevated) and
      pCO2 (compensatory) elevation. To establish the causes it is necessary to
      determine intravascular volume, supine and standing blood pressure and renin
      angiotension alolosterone axis. In chloride responsive alkalosis in which the
      conditions are extracellular volume depletion, hypokalaemia and hypochloraemia
      correction of intravascular volume with sodium chloride is needed. In severe
      metabolic alkalosis of any cause dilute hydrochloric acid (0.1 N HCl) may be
      infused intravenously but haemolysis may be a complication. In emergency
      situation with severe hypokalaemia dialysis with higher K+, Cl- and low HCO3-
      bath will be appropriate.

PMID- 17444064
TI  - Kluver-Bucy syndrome--a rare complication of herpes simplex encephalitis.
AB  - A twelve-year-old female was admitted with history of high fever, recurrent
      vomiting and repeated convulsion for 2 days and altered consciousness for one
      day. Cranial CT scan showed intraparenchymal haemorrhage involving both temporal
      lobes and right basal ganglia region without mass effect. Serology was reactive
      against IGM HSV1. Injection acyclovir was started at a dose of 10 mg/kg 8 hourly
      intravenously. Patient regained consciousness on fourth day but speech was
      altered. Abnormal behavioural symptoms were noticed. EEG showed generalised spike
      and slow waves and sharp and slow wave discharge more in the temporal region. The
      patient was given clonidine and carbamazepine. She also received behavioural
      therapy and parental counselling. She was followed up for six months and
      maintaining well.

PMID- 17444065
TI  - Myelodysplastic syndrome in pregnancy--a rare cause of severe anaemia in
      pregnancy.
AB  - A 28-year-old woman presented with severe anaemia in pregnancy at a period of
      gestation of 20 weeks. She was immediately admitted and after proper
      investigation it was seen that her Hb was 3.5 g/dl and platelet count was
      62,000/cmm, RBC showed normocytic, normochromic morphology. There was neither
      hepatosplenomegaly nor any purpuric spot over the body. Bone marrow showed
      dyserythropoiesis and its chromosomal study revealed monosomy-7. Her pregnancy
      was continued till term with repeated packed cell and platelet concentrate
      transfusions. Normal healthy baby was delivered by caesarean section and she was
      discharged after 6 days.

PMID- 17444066
TI  - Imipramine in persistent vomiting.
AB  - A 21-year-old female presented with persistent vomiting for last 3 years. She had
      all the investigations done including gastroscopy but there was no abnormality
      detected. She was tried earlier with medicines prescribed in a medical college or
      a private nursing home. The cause of vomiting was thought of psychogenic. She was
      advised imipramine 25 mg thrice daily and responded to the treatment favourably.

PMID- 17444067
TI  - Metastasis--an unusual cause of retroperitoneal fibrosis.
AB  - Retroperitoneal fibrosis is one of the rare fibrotic processes mainly involving
      caudal aspect of the retroperitoneum. In up to 70% of patients no causative
      factor for retroperitoneal fibrosis can be identified, where it resembles auto
      immune reaction. A 30-year-old lady presented with progressive oedema of the
      lower extremities, jaundice and abdominal swelling. Clinical examination revealed
      doughy abdominal feel and diffuse tenderness. Ultrasonography showed dilated
      intrahepatic bilary radicles and mild ascites. Contrast CT-scan showed enhancing
      sheath of soft tissue extending from porta down to aortic bifurcation encasing
      common bile duct, aorta, inferior vena cava and the ureters. CT-guided fine
      needle aspiration cytology revealed metastatic adenocarcinoma. Ascitic fluid did
      not show any malignant cell. No abdominal mass could be detected. The patient
      died during the course of palliative chemotherapy.

PMID- 17444068
TI  - Uncomplicated falciparum malaria complicated by salmonella septicaemia: cause not
      coincidence.
AB  - A male patient of 10-year-old presented with fever, headache and vomiting for
      last few days. He was being treated with antimalarial drugs. On 14th day of
      illness he again showed rise of temperature. His blood culture showed growth of
      Salmonella typhi. He was treated with ceftriaxone and responded favourably. Here
      uncomplicated falciparum malaria developed a secondary infection with salmonella
      during hospital stay. This uncommon association was noted rather than a mere
      coincidence, which rarely reported in literature.

PMID- 17444069
TI  - Continuous arteriovenous haemofiltration to regulate hyperkalaemia during renal
      transplantation: a case report.
AB  - Progressive hyperkalaemia is common in end stage renal disease patients waiting
      for renal transplantation. Ventricular tachycardia and ventricular fibrillation
      due to hyperkalaemia are life-threatening complications in these patients. In
      live and related renal transplant, after induction and anaesthesia, ventricular
      fibrillation and pulmonary oedema occurred. After immediate resuscitation by
      defibrillation and intravenous injection of adrenaline, the patient was put on
      continuous femoral arteriovenous haemofiltration (CAVH). This improved his
      pulmonary oedema, controlled hyperkalaemia and surgery could be completed
      uninterruptedly. After anaesthetising live and related kidney donor for
      nephrectomy, since it is not prudent to stop recipient surgery because of
      unforeseen complication, the authors wish to recommend CAVH as an alternative
      method to prevent life threatening cardiac complication of hyperkalaemia.

PMID- 17444071
TI  - Hidden risks.

PMID- 17444070
TI  - A postmarketing observational study assessing acceptability and reliability of
      desogestrel only contrapceptive pill (Cerazette) in Indian women.
AB  - A postmarketing observational study was carried out in a prospective, open and
      multi-centric manner monitoring a treatment period of 4 cycles (4 x 28 days)
      among Indian women of child bearing age to determine the acceptability and
      reliability of desogestrel (75 microg/day), an oestrogen-free pill. It involved
      299 subjects recruited at each of 20 centres spread all over India. The study
      duration for each subject was 16 weeks with follow-up visits at 4, 8 and 16 weeks
      intervals. At each follow-up visit, subjects were evaluated for any failure of
      contraception, change in bleeding pattern and other adverse events. Of the study
      subjects, 238 (79.6%) continued the study for 4 cycles and were thus considered
      eligible for analysis of bleeding patterns with no failure of contraception. In
      addition, the physician's as well as patient's global assessment, demonstrated a
      "very good" response in majority of subjects (> 84%). A sizeable number of cases
      (47.9%) had infrequent episodes (1 to 5) of bleeding--spotting during the shifted
      reference period, while 41.2% experienced amenorrhoea. There was no clinically
      significant change in blood pressure or body weight. Of the 299 such subjects
      enrolled, 53 subjects were lost to follow-up and did not come for the 1st follow
      up visit. Hence, out of the 246 subjects, 21.1% presented with 78 separate
      adverse events during 960 treatment cycles. None of the reported adverse events
      were severe and there was not even a single serious adverse effect during the
      course of the study. Nausea, breast tenderness and headache (7.7%, 10.1% and 9.7%
      respectively) were the most frequent adverse events observed during the study.
      Desogestrel 75 mg/day was well accepted in majority of Indian women. It provides
      good contraceptive efficacy, with a lower incidence of irregular bleeding and
      spotting episodes.

PMID- 17444072
TI  - New developments in cognitive-behavioural therapy for mood disorders.

PMID- 17444073
TI  - Advances in cognitive-behavioural therapy for unipolar depression.
AB  - OBJECTIVE: To describe the main innovations in our theoretical understanding of
      depression and key clinical developments in cognitive-behavioural therapy (CBT).
      We outline the current status of CBT and discuss how it can respond to the public
      health problem of depression. METHOD: We undertook a narrative literature review.
      RESULTS: CBT provides a sophisticated, empirically grounded account of depression
      and an evidence-based therapeutic approach for people who suffer from depression.
      Beyond its efficacy in treating acute depression, it has prophylactic effects and
      is acceptable to various populations in a range of settings. Good theoretical
      accounts of the emergence of depression in adolescence are forthcoming; to date,
      however, attempts at primary prevention are unconvincing. Our understanding of
      factors contributing to positive outcomes is growing, allowing CBT to be tailored
      to individual client needs. CONCLUSIONS: CBT is a mainstay approach to
      depression. Significant remaining challenges include tailoring it to different
      populations and settings and, most importantly, ensuring that it is more readily
      accessible.

PMID- 17444074
TI  - How well do psychosocial interventions work in bipolar disorder?
AB  - OBJECTIVE: Although medication is the mainstay of treatment for bipolar disorder,
      several adjunctive psychosocial interventions have been manualized over the last
      decade. This paper's objective is to empirically evaluate the different treatment
      approaches. METHOD: We conducted a systematic review of the recent literature
      pertaining to psychosocial interventions in bipolar, using MEDLINE and PsycINFO.
      Bibliographies of papers were scrutinized for further relevant references.
      Articles published from 1999 up to and including 2006 were reviewed. Randomized
      controlled trials were emphasized. CONCLUSIONS: Although psychological models of
      bipolar disorder fail to inform the psychotherapy treatment to the same extent as
      in unipolar depression, manualized adjunctive, short-term psychotherapies have
      been shown to offer fairly consistent benefits to bipolar disorder patients.
      Cognitive-behavioural therapy, family-focused therapy, and psychoeducation offer
      the most robust efficacy in regard to relapse prevention, while interpersonal
      therapy and cognitive-behavioural therapy may offer more benefit in treating
      residual depressive symptoms.

PMID- 17444075
TI  - Screening for mental health problems among patients with substance use disorders:
      preliminary findings on the validation of a self-assessment instrument.
AB  - OBJECTIVES: We conducted a preliminary study on the validation of the Psychiatric
      Diagnostic Screening Questionnaire (PDSQ) among patients seeking treatment for
      substance use disorders (SUDs). METHOD: We assessed 76 patients with SUDs, using
      the PDSQ, followed by the Structured Clinical Interview for DSM-IV. Sensitivity,
      specificity, positive and negative predictive values, and receiver operating
      characteristic (ROC) curves were calculated. RESULTS: Overall, the psychometric
      properties identified with the PDSQ in patients with SUDs differed from those
      found in psychiatric outpatient populations. The ROC curves were calculated for
      major depressive disorder, posttraumatic stress disorder, and panic disorder. The
      areas under the curves were 0.86 (95% CI, 0.77 to 0.95; P < 0.001), 0.79 (95% CI,
      0.68 to 0.90; P < 0.001), and 0.66 (95% CI, 0.51 to 0.82; P = 0.05),
      respectively. CONCLUSION: The use of the PDSQ to screen for other psychiatric
      disorders in populations with SUDs is promising but requires larger validation
      studies to provide data on its psychometric properties and inform the choice of
      cut-off scores for this population.

PMID- 17444076
TI  - The prevalence and incidence of treated major depressive disorder among National
      Health Insurance enrollees in Taiwan, 1996 to 2003.
AB  - OBJECTIVE: We used the National Health Insurance (NHI) database to examine the
      prevalence and incidence of treated major depressive disorder (MDD) and their
      associated factors. METHOD: The National Health Research Institute provided a
      database of 200 432 randomly selected subjects for study. We obtained a
      population-based random sample aged 15 years or older (n = 136 045) as a fixed
      cohort dated 1996 to 2003. We identified study subjects with a principal
      diagnosis of MDD who had at least one service claim during these years for either
      ambulatory or inpatient care. RESULTS: From 1996 to 2003, the cumulative treated
      prevalence increased from 1.67 per 1000 to 17.24 per 1000. From 1997 to 2003, the
      annual treated incidence increased from 1.89 per 1000 to 2.58 per 1000. A higher
      incidence of treated MDD was detected in the groups aged 25 to 44 years (hazard
      ratio [HR] 1.28; 95% confidence interval [CI], 1.13 to 1.45), 45 to 64 years (HR
      1.90; 95% CI, 1.66 to 2.16), and 65 years or older (HR 1.87; 95% CI, 1.59 to
      2.20); in female subjects (HR 1.97; 95% CI, 1.80 to 2.15); in those with with an
      insurance amount of US $1281 or more (HR 1.15; 95% CI, 1.01 to 1.31); in those
      with a fixed premium (HR 1.44; 95% CI, 1.27 to 1.62); and among those who lived
      in urban areas (HR 1.22; 95% CI, 1.10 to 1.35). CONCLUSIONS: For treated MDD, the
      prevalence and incidence in Taiwan were lower than in community studies in
      Western countries. Individuals with MDD are underdiagnosed and undertreated in
      Taiwan.

PMID- 17444077
TI  - Structured assessment of mental health status in psychogeriatrics: validity of
      the French HoNOS65+.
AB  - OBJECTIVE: To assess the reliability, validity, and feasibility of a French
      version of the Health of the Nation Outcome Scales for Elderly People (HoNOS65+).
      METHOD: Twenty mental health professionals completed the scale for 126 elderly
      patients. We assessed interrater reliability in inpatient and outpatient
      settings, together with construct and discriminant validity, as well as
      concurrent validity compared with several widely used clinical instruments.
      RESULTS: Excellent agreement among raters was observed in the outpatient subgroup
      (kappa range 0.77 to 1.00), whereas interrater reliability was modest in the
      inpatient subgroup (kappa values < 0.55). In cases where the patient-caregiver
      relationship lasted more than 1 month, the reliability of the scale improved.
      Construct validity analysis revealed no subscale structure. All items except
      "self-injury" displayed high concurrent validity (significant Spearman
      correlations with 8 other questionnaires). In terms of discriminant validity, the
      "cognitive impairment" (area under the curve [AUC] 0.91) and "depressive
      symptoms" (AUC 0.79) items showed high sensitivity and specificity values.
      CONCLUSION: Our results indicate that the French version of HoNOS65+ is a
      promising clinical assessment tool to evaluate mental disorders in the elderly in
      outpatient settings. We support its use in routine clinical practice, with the
      condition that a relatively long and individualized patient-caregiver
      relationship has been established.

PMID- 17444078
TI  - Definition, assessment, and staging of treatment-resistant refractory major
      depression: a review of current concepts and methods.
AB  - OBJECTIVE: Up to 15% of depression patients eventually present with treatment
      resistant or refractory depression (TRD), a condition that causes significant
      social and economic burdens. Our paper aims to summarize the current medical
      literature on the conceptual and methodologic issues involved in the definition,
      assessment, and staging of TRD. METHOD: We reviewed the recently published
      medical literature to identify papers that specifically discuss TRD. For this, we
      searched MEDLINE, EMBASE, and PsycINFO for potentially relevant English-language
      articles published between January 1996 and June 2006. RESULTS: Recent
      methodologic and conceptual advances have contributed to the achievement of an
      acceptable level of theoretical consensus on the general meaning of TRD.
      Accordingly, depression is usually considered resistant or refractory when at
      least 2 trials with antidepressants from different pharmacologic classes
      (adequate in terms of dosage, duration, and compliance) fail to produce a
      significant clinical improvement. Regarding diagnostic assessments, an accurate
      and systematic evaluation should be made to elicit the potential role of several
      contributing factors, such as medical and psychiatric comorbidity. CONCLUSION:
      Recently, 3 staging methods for TRD have been described, but they currently
      require extensive empirical support. Future research on TRD should include
      prospective studies addressing the validity of the proposed criteria, the impact
      of depression comorbid with other psychiatric disorders and (or) physical
      conditions, and the possible predictors o treatment outcome. There is an
      important and clear need for studies that empirically test current definitions,
      assessment strategies, and staging methods of TRD.

PMID- 17444079
TI  - An outcome measure in schizophrenia: mortality.
AB  - OBJECTIVE: To determine the current outcome of schizophrenia, with mortality rate
      as the outcome measure. METHOD: Recent health, suicide, victim of violence, and
      mortality statistics were reviewed. RESULTS: The general health of individuals
      with schizophrenia suffers from neglect, poor life style choices, and current
      treatments that increase death rates. CONCLUSION: Mortality in schizophrenia is
      rising, and it is the responsibility of physicians and health care planners to
      intervene.

PMID- 17444080
TI  - Comparison of the Child Behavior Checklist Profiles between community- and clinic
      based children with attention deficit hyperactivity disorder in Korea.
AB  - OBJECTIVE: The aim of this study was to examine whether there is a difference in
      the behavioural characteristics of community- and clinic-based children with
      attention-deficit hyperactivity disorder (ADHD) in Korea. METHOD: The study
      included 75 community-based and 72 clinic-based subjects with ADHD. The parents
      of all the children completed the parent versions of the Child Behavior Checklist
      (CBCL). RESULTS: The community-based ADHD subjects scored significantly higher (P
      < 0.01) than clinic-based subjects in the Somatic Complaints and Delinquent
      Behaviour profiles of the CBCL. The community-based subjects with ADHD, combined
      subtype, showed significantly higher mean scores in the Somatic Complaints (P <
      0.01) and Thought Problems (P < 0.05) profiles than the clinic-based subjects
      with ADHD, combined subtype. CONCLUSION: These findings suggest the possibility
      of an increased incidence of behavioural or emotional problems in community-based
      ADHD subjects when compared with clinic-based subjects in Korea.

PMID- 17444081
TI  - Advances in exposure with response prevention.

PMID- 17444082
TI  - Medicare retiree drug subsidy compliance considerations.
AB  - Employers and plan sponsors have struggled with many issues associated with
      Medicare's retiree drug subsidy program. Recent reviews of employer methods for
      collecting the subsidy from the Centers for Medicare and Medicaid Services (CMS)
      identified significant gaps that would affect the subsidy payment and create
      issues in case of an audit. In fact, the Department of Health and Human Services
      Office of Inspector General (OIG) has placed audits of employer retiree drug
      subsidy processes in its work plans for 2006 and 2007. This article discusses
      areas that employers must address now to avoid significant long-term financial
      and compliance problems in the future.

PMID- 17444083
TI  - Federal jurisdiction--reimbursement action by federal employee health plan
      administrator. Empire HealthChoice Assurance, Inc., d/b/a Empire Blue Cross Blue
      Shield v. McVeigh.
AB  - The Supreme Court, in a 5-4 decision, ruled that federal courts lack jurisdiction
      over a suit brought by a federal employee health plan administrator seeking
      reimbursement of benefits covered by a personal injury settlement.

PMID- 17444084
TI  - Federal employees--random drug and alcohol testing--subject matter jurisdiction-
      issue preclusion--exhaustion. Whitman v. Department of Transportation.
AB  - The Supreme Court, in a per curium decision, vacated a ruling against an air
      traffic controller in his claim that he was subjected to more than random drug
      testing and remanded the matter to the Ninth Circuit to determine whether the
      petitioner exhausted his administrative remedies and whether exhaustion is
      required, or, if necessary, whether the Civil Service Reform Act precludes
      employees from pursuing claims beyond those set out in that act, i.e., whether
      Congress intended to remove such actions from the general grant of subject matter
      jurisdiction under 28 U.S.C. paragraph 1331.

PMID- 17444085
TI  - Measurement of combined corneal, internal, and total ocular optical quality
      analysis in anterior segment pathology with the OPD-scan and OPD-station.
AB  - PURPOSE: To show the clinical use of the NIDEK OPD-Scan wavefront aberrometer and
      OPD-Station software in anterior segment surgery and pathology. METHODS: Case
      examples are presented along with discussion about the relevant clinical data
      obtained from the OPD-Scan and OPD-Station software. RESULTS: Six case examples
      including cataract surgery, secondary IOL implantation, phakic intraocular lens
      surgery, pterygium surgery, contact lens fitting, and multifocal ablations are
      discussed. CONCLUSIONS: A complete understanding of the optics of the eye
      facilitates a better clinical comprehension of a variety of conditions in
      anterior segment surgery and pathology.

PMID- 17444086
TI  - Precision of NIDEK OPD-scan measurements.
AB  - PURPOSE: To evaluate the repeatability of wavefront measurements using the NIDEK
      OPD-Scan. METHODS: A total of 179 eyes from 90 healthy volunteers (57 women and
      33 men) with no corneal or lenticular pathology and normal visual acuity were
      enrolled in this study. Mean patient age was 39 years (range: 17 to 85 years).
      All patients underwent four consecutive measurements by one examiner with the
      NIDEK OPD-Scan. Total, corneal, and internal wavefront errors were measured and
      calculated with the device, using slit retinoscopy. Repeatability of the
      measurements was evaluated for spherical aberration, coma, and trefoil. RESULTS:
      The repeatability test revealed a good result for all three higher order
      aberrations evaluated. The best repeatability values were found for total
      aberrations, followed by internal and corneal aberrations. CONCLUSIONS: The NIDEK
      OPD-Scan has good precision in the wavefront measurement of total, corneal, and
      internal optical aberrations.

PMID- 17444087
TI  - Wavefront analysis in Asian-Brazilians.
AB  - PURPOSE: To compare the distribution of ocular higher order wavefront aberrations
      (third to sixth order) in the Brazilian population of Asian and non-Asian
      refractive surgery patients. METHODS: Preoperative refractive and wavefront data
      were reviewed for 648 eyes in 324 patients who underwent custom ablation at the
      Excimer Laser Santa Cruz refractive surgery center in Sao Paulo, Brazil, from
      March 2002 to July 2005. Patients were divided into two groups: Asian patients
      and non-Asian patients, based on family history. Statistical analysis was
      performed to assess the differences between the groups with respect to manifest
      refractive spherical equivalent, astigmatism, pachymetry, OPD-root-square-mean
      (RMS) for a 6.0-mm pupil, total wavefront aberrations, third- to sixth-order
      higher order aberrations, and individual aberrations. RESULTS: The mean spherical
      equivalent refraction in the Asian group of -4.38 diopters (D) was significantly
      higher than the spherical equivalent refraction of -3.46 D in the non-Asian group
      (t= -4.32; P=.00001). Comparison of the differences between groups with respect
      to higher order aberrations, coma, trefoil, quadrafoil, spherical aberration,
      higher order astigmatism, and pachymetry was not statistically significant.
      CONCLUSIONS: Asian patients have a higher prevalence of myopia than non-Asian
      patients. No differences were noted in higher order aberrations between Asian and
      non-Asian patients.

PMID- 17444088
TI  - Comparison of measurement of pupil sizes among the colvard pupillometer, procyon
      pupillometer, and NIDEK OPD-scan.
AB  - PURPOSE: To compare pupil sizes measured with the Colvard pupillometer, Procyon
      pupillometer, and NIDEK OPD-Scan. METHODS: Pupil diameter was measured in 90
      consecutive eyes from 55 patients under mesopic and scotopic light conditions
      with all three instruments. RESULTS: The mean scotopic pupil diameter was 6.3+/
      0.98 mm with the Colvard pupillometer and 6.45+/-1.01 mm with the Procyon
      pupillometer. The mean mesopic pupillometer was 5.58+/-1.01 mm with the Procyon
      pupillometer and 6.26-0.99 mm with the CONCLUSIONS: The mesopic pupil diameter
      measured with the NIDEK OPD-Scan is more consistent with the scotopic pupil
      diameter measured with the Procyon and Colvard pupillometers than the mesopic
      pupil diameter measured with the Procyon pupillometer.

PMID- 17444089
TI  - Optical quality analysis after surface excimer laser ablation: the relationship
      between wavefront aberration and subepithelial haze.
AB  - PURPOSE: To investigate the relationship between mild and moderate corneal haze
      and the distribution of higher order wavefront aberrations after photorefractive
      keratectomy (PRK). METHODS: Thirty-six eyes from 18 patients who underwent PRK
      were divided into two groups: 10 eyes with corneal haze and 26 eyes without
      corneal haze (control). All eyes were evaluated up to 6 months after PRK.
      Wavefront aberrations were measured using a psychophysical wavefront sensor and
      the NIDEK OPD-Scan. Topography, point spread function, and modulation transfer
      function maps were obtained from the OPD-Scan. RESULTS: The mean total higher
      order aberration was slightly higher in the corneal haze group than in the
      control group. This difference was not statistically significant. The mean third
      order coma aberrations were higher and mean fourth order spherical aberrations
      were lower in the haze group compared with the control group, although neither
      difference attained statistical significance. The t test values were 1.05, -0.38,
      -1.10, -0.08, and -0.23, when comparing the mean third, fourth, fifth, sixth, and
      seventh order aberrations, respectively. None of these differences attained
      statistical significance. In terms of Zernike coefficients, Z-1 and Z1 showed
      greater mean root-mean-square (RMS) in the haze group (0.33 and 0.35 microm,
      respectively) than those for the control group (0.26 and 0.23 microm,
      respectively) (t=0.71 and P=.49; t=0.84 and P=.43, respectively). However, ZO had
      lower RMS in the haze group (0.18 microm) than in the control group (0.28
      microm). This difference also was not statistically significant. CONCLUSIONS: In
      this study comparing the optical aberrations of eyes with and without corneal
      haze after PRK, corneal haze did not affect the magnitude and distribution of
      higher order aberrations in a predictable manner.

PMID- 17444090
TI  - Precision of higher order aberration repeatability with NIDEK OPD-scan
      retinoscopic aberrometry.
AB  - PURPOSE: To evaluate repeatability of the total high order aberrations with a
      retinoscopic wavefront sensor. METHODS: This prospective case series analyzed 12
      eyes from 6 patients who underwent wavefront measurement using retinoscopic
      aberrometry with the NIDEK Optical Path Difference Scan (OPD-Scan). Four
      consecutive wavefront measurements of each eye were taken by two trained
      examiners for 5.8+/-0.8-mm and 8.2+/-0.6-mm pupils (P=.002, Wilcoxon test). Total
      high order aberrations out to the eighth order were assessed including third
      order coma, third order trefoil, fourth order quadrafoil, fourth order secondary
      astigmatism, and fourth order spherical aberrations. Differences between
      measurements of all of the variables were analyzed. A P value <.05 was considered
      statistically significant. RESULTS: Repeatability analysis of the root-mean
      square of total higher order aberrations, coma, trefoil, quadrafoil, secondary
      astigmatism, and spherical aberrations for both dilated and nondilated pupils did
      not show a statistically significant difference among all repeated measurements,
      except for trefoil and secondary astigmatism (analysis of variance and the
      Friedman test). The repeatability of total higher order aberrations was 0.15
      microm for nondilated pupils and 0.18 microm for dilated pupils. Except for
      trefoil measurements, all high order aberrations showed reproducibility >0.15
      microm when Zernike coefficients were analyzed individually. CONCLUSIONS: The
      NIDEK OPD-Scan aberrometer measures total higher order astigmatism and most
      individual aberrations with acceptable repeatability. However, measurement of
      trefoil with this instrument is less repeatable.

PMID- 17444091
TI  - Clinical use of in vivo confocal microscopy through focusing in corneal
      refractive surgery.
AB  - PURPOSE: To illustrate the use of in vivo confocal microscopy through focusing to
      observe normal cornea and corneal wound healing after excimer laser refractive
      surgery. METHODS: A total of 197 eyes, including both unoperated eyes and eyes
      that had undergone LASIK, photorefractive keratectomy (PRK), or laser epithelial
      keratomileusis (LASEK), were examined using in vivo confocal microscopy through
      focusing. Images of the various corneal layers resolved by confocal microscopy
      through focusing were recorded and analyzed. Pachymetry of the cornea,
      epithelium, and stroma was also recorded for all eyes. The t test was used to
      evaluate the differences between unoperated eyes and postoperative eyes and the
      change in corneal pachymetry preoperatively to postoperatively with each type of
      surgery. A P value <.05 was considered statistically significant. RESULTS: Each
      layer of the cornea could be resolved in unoperated eyes and eyes that had
      undergone refractive surgery. Wound healing could be followed over time using
      confocal microscopy through focusing. In eyes that underwent PRK, at 1 month
      postoperatively, the entire cornea and stroma were thinner than preoperatively,
      whereas the epithelial layer was statistically significantly thicker (P<.05).
      Haze after PRK is seen as reflectivity of subepithelial anterior stroma. No
      clinically significant haze was observed in eyes that underwent LASEK or LASIK.
      The features of the eyes that underwent LASIK were the same as those of
      unoperated eyes. CONCLUSIONS: Confocal microscopy through focusing was useful in
      documenting cellular morphology in unoperated corneas and corneas that had
      undergone refractive surgery. Wound-healing characteristics of eyes that had
      undergone refractive surgery were also documented using confocal microscopy.

PMID- 17444092
TI  - Corneal diabetic neuropathy: a confocal microscopy study.
AB  - PURPOSE: To evaluate the role of corneal confocal microscopy in the diagnosis of
      morphologic damage of the corneal sub-basal nerve plexus in diabetic patients and
      to correlate corneal confocal microscopy findings with peripheral diabetic
      neuropathy. METHODS: Corneal sub-basal nerve plexus parameters were quantified by
      corneal confocal microscopy in 42 diabetic patients and 27 age-matched controls.
      The parameters quantified were the number of fibers, the tortuosity of fibers,
      the number of beadings, and the branching pattern of the fibers. Peripheral
      neuropathy was also quantified using the Michigan Neuropathy Screening
      Instrument. RESULTS: The number of fibers, number of beadings, and branching
      pattern of fibers significantly decreases in diabetic patients versus control
      subjects (P<.0001; P<.0001; P=.0006, respectively), whereas nerve tortuosity
      significantly increases (P<.0001). The same corneal sub-basal nerve plexus
      parameters show a statistical trend, suggesting progression of corneal neuropathy
      with peripheral diabetic neuropathy. CONCLUSIONS: Corneal confocal microscopy
      represents a new tool in the diagnosis, clinical evaluation, and follow-up of
      peripheral diabetic neuropathy. This study found that diabetes damages corneal
      nerves, particularly the corneal sub-basal nerve plexus. This damage may be
      easily and accurately documented using corneal confocal microscopy.

PMID- 17444093
TI  - Improvement of best spectacle-corrected visual acuity after LASIK in highly
      myopic eyes with reduced preoperative best spectacle-corrected visual acuity.
AB  - PURPOSE: To evaluate the visual acuity after LASIK in patients with high myopia
      and in patients with preoperative best spectacle-corrected visual acuity (BSCVA)
      <0.6. METHODS: This retrospective study comprised 97 consecutive eyes in 57
      patients who underwent LASlK. Preoperative spherical refractive error ranged from
      -1.75 to -22.00 diopters (D) (mean: -11.77+/-3.61 D) with mean astigmatism of 
      1.54+/-10.6 (range: 0 to -4.00 D). Pre- and postoperative BSCVA and uncorrected
      visual acuity (UCVA) were measured and analyzed. RESULTS: The mean preoperative
      BSCVA was 0.54+/-0.07 (range: 0.3 to 0.6). The mean postoperative BSCVA was
      0.75+/-0.16 (range: 0.5 to 1.2). The mean postoperative UCVA was 0.60+/-0.25
      (range: 0.5 to 1.2). A statistically significant improvement was noted in the
      mean postoperative BSCVA compared with the mean preoperative BSCVA (t=12.78;
      P<.001) and mean postoperative UCVA compared with preoperative mean BSCVA
      (t=2.866; P<.01). The safety index was 1.38, which was statistically significant
      (P<.001). The efficacy index was 1.11, which was statistically significant
      (P<.01). CONCLUSIONS: LASIK improved the mean postoperative BSCVA and UCVA
      compared with preoperative BSCVA in highly myopic eyes with reduced BSCVA.

PMID- 17444094
TI  - Optical factors in increased best spectacle-corrected visual acuity after LASIK.
AB  - PURPOSE: To study the factors that correlate with improved best spectacle
      corrected visual acuity (BSCVA) after LASIK. METHODS: This was a nonrandomized,
      prospective clinical trial of 850 eyes from 480 patients undergoing LASIK for
      myopia, hyperopia, and mixed astigmatism. The mean preoperative spherical
      equivalent refraction was -3.75+/-4.82 diopters (D) (range: -13.88 to 6.00 D).
      From this population, 72 eyes (including 22 amblyopic eyes) from 43 patients were
      found to have improved BSCVA 6 months after LASIK. All patients underwent LASIK
      with the NAVEX platform. These eyes were analyzed to evaluate factors that
      correlated with improved BSCVA. Pre- and postoperative BSCVA, refraction, pupil
      diameter, corneal topography, asphericity (Q value), total aberrations, and
      higher order wavefront aberrations were analyzed. All wavefront aberrations were
      measured using the NIDEK Optical Path Difference Scan aberrometer (OPD-Scan)
      preoperatively and at 6 months postoperatively. RESULTS: Postoperatively, the
      mean sphere was -0.44 1.30 D (range: -4.50 to +2.50 D). The mean increase in
      BSCVA was 0.15+/-0.09 logMAR. A statistically significant negative correlation
      was observed between the increase in BSCVA and the preoperative BSCVA (P<.01).
      Mixed astigmatic and highly myopic eyes are more likely to gain BSCVA after LASIK
      than moderately myopic (P<.05) and hyperopic eyes (P<.001). In patients with
      myopia, the amount of BSCVA improvement correlated with the magnitude of the
      correction (P<.05). The induction of spherical aberration negatively correlated
      with the increase in BSCVA (P<.05). There were no significant differences between
      normal eyes and amblyopic eyes with respect to postoperative improvement in BSCVA
      (P>.05). CONCLUSIONS: Decreased preoperative BSCVA, lower total spherical
      aberration induction, and preoperative mixed astigmatism and high myopia
      correlate with an increase in BSCVA after LASIK.

PMID- 17444095
TI  - LASIK using the NIDEK EC-5000 for the correction of hyperopic astigmatism.
AB  - PURPOSE: To assess the refractive outcomes of LASIK for the surgical correction
      of hyperopic astigmatism using the NIDEK EC-5000 excimer laser. METHODS: LASIK
      was performed on 46 eyes from 26 patients (19 men and 7 women) for the correction
      of congenital hyperopic astigmatism. The NIDEK EC-5000 excimer laser and the
      Moria M2 microkeratome were used in all procedures. Cylindrical ablations were
      performed on the negative axis out to a 6-mm diameter. RESULTS: The mean
      preoperative cylindrical refraction was +3.15+/-0.70 diopters (D) (range: +1.75
      to +4.50 D), and the mean 24-month postoperative refraction was +1.27+/-0.78 D
      (range: +0.50 to +3.25 D). Vector analysis showed a 2.17+/-1.27 D reduction in
      the equivalent cylinder. Preoperative mean uncorrected visual acuity (UCVA) was
      20/100, and 24-month postoperative UCVA was 20/30. One eye lost one line of best
      spectacle-corrected visual acuity at 24 months postoperatively. Complications
      related to the LASIK flap occurred in 2 (4.3%) eyes. Partial regression of the
      astigmatic effect began at 4 to 6 months but stabilized by 1 year. CONCLUSIONS:
      LASIK is a safe but limited alternative for the correction of astigmatism in eyes
      with hyperopic astigmatism. Early regression of the astigmatic effect in the
      first 6 months seems to be the primary disadvantage of this technique.

PMID- 17444096
TI  - Correction of high astigmatism: case studies using the mixed-cylinder approach.
AB  - PURPOSE: To explain the use of the mixed-cylinder approach in treating moderate
      to high astigmatism with the NIDEK EC-5000 excimer laser system. METHODS:
      Retrospective case series report. RESULTS: Three patients with bilateral moderate
      to high astigmatism were treated successfully using the mixed cylinder approach.
      CONCLUSIONS: The use of the mixed-cylinder approach with the NIDEK EC-5000
      excimer laser may be a safe and predictable option for treating moderate to high
      astigmatism.

PMID- 17444097
TI  - Corneal astigmatism, high order aberrations, and optical quality after cataract
      surgery: microincision versus small incision.
AB  - PURPOSE: To compare the astigmatism, high order aberrations, and optical quality
      of the cornea after microincision (approximately 1.7 mm) versus small incision
      approximately 3.2 mm) cataract surgery at Eye Center, Zhejiang University,
      Hangzhou, China. METHODS: This prospective, randomized clinical study included
      microincision cataract surgery and small incision cataract surgery performed on
      60 eyes. Corneal astigmatism and higher order aberrations to the sixth order were
      measured using the NIDEK OPD-Scan aberrometer/topographer 1 month after surgery.
      To evaluate the optical quality of the cornea, the 0.5 modulation transfer
      function (MTF) value and 0.1 MTF value within a 5-mm pupil were calculated using
      OPD-Station software. Statistical analysis assessing the difference between
      groups was carried out using the independent t test. RESULTS: The mean corneal
      astigmatism was significantly lower after microincision cataract surgery compared
      with small incision cataract surgery (0.78+/-0.38 diopters [D] vs 1.29+/-0.68 D,
      respectively; P=.001). No significant differences were found between the two
      groups for the root-mean-square value of total high order aberrations or
      individual high order aberrations for spherical aberration, coma, and trefoil.
      However, eyes that underwent microincision cataract surgery showed statistically
      significantly better optical performance with a 0.5 MTF value than eyes that
      underwent small incision cataract surgery (3.13+/-0.30 cycles per degree [cpd] vs
      2.75+/-0.63 cpd, respectively; P=.005). The 0.1 MTF values for the two groups
      were 9.37+/-3.72 cpd for microincision cataract surgery and 7.24+/-3.43 cpd for
      small incision cataract surgery, which was not significantly different (P=.136).
      CONCLUSIONS: Microincision cataract surgery generates statistically significantly
      less corneal astigmatism and better optical quality of the cornea by MTF
      evaluation compared with small incision cataract surgery. However, microincision
      cataract surgery shows no significant advantage in reducing corneal high order
      aberrations over small incision cataract surgery.

PMID- 17444098
TI  - Changes in corneal astigmatism and high order aberrations after clear corneal
      tunnel phacoemulsification guided by corneal topography.
AB  - PURPOSE: To study changes in corneal astigmatism and high order aberrations after
      clear corneal tunnel phacoemulsification guided by corneal topography. METHODS:
      All patients were randomly assigned to the test group or the control group.
      Corneal topography-guided clear corneal tunnel phacoemulsification followed by
      intraocular lens (IOL) implantation was performed on 22 eyes of 16 patients in
      the test group and conventional temporal corneal tunnel phacoemulsification and
      IOL implantation were performed on 22 eyes of 21 patients in the control group.
      The corneal astigmatism and high order aberrations were measured using the NIDEK
      OPD-Scan aberrometer and topographer preoperatively and up to 3 months after
      surgery. The corneal astigmatism and sixth order root-mean-square (RMS) for
      corneal coma, trefoil, spherical, secondary coma, and secondary spherical
      aberrations at 4-mm pupil diameters were compared. RESULTS: Fifteen (69%) eyes in
      the test group and 8 (36%) eyes in the control group achieved > or =20/25
      uncorrected visual acuity 3 months after surgery, which was statistically
      significant (P<.05). The best spectacle-corrected visual acuity was > or =20/20
      in 14 (63%) eyes in the test group and 10 (45%) eyes in the control group. The
      mean surgically induced astigmatism in the test group was 0.58+/-0.39 diopters
      (D) compared with 0.73+/-0.41 D in the control group. The change in corneal
      astigmatism from preoperative to 3 months after surgery was -0.17+/-0.32 D for
      the test group and 0.10+/-0.41 D for the control group, which was statistically
      significant (P<.05). The RMS value of trefoil aberrations increased, and all
      other aberrations decreased at 3 months after surgery in the test group. The RMS
      values of all corneal high order aberrations increased in the control group, with
      the increase in trefoil being statistically significant. The comparison of
      surgically induced high order aberrations between the two groups showed that
      corneal coma, trefoil, and secondary coma were significantly different.
      CONCLUSIONS: Clear corneal tunnel phacoemulsification and IOL implantation guided
      by corneal topography can yield better visual acuity by reducing the pre-existing
      astigmatism and inducing less corneal aberrations than conventional temporal
      corneal tunnel phacoemulsification.

PMID- 17444100
TI  - Where doctors go wrong.

PMID- 17444099
TI  - Automated visual axis alignment for refractive excimer laser ablation.
AB  - PURPOSE: To describe the use of new laser alignment and delivery software in the
      NIDEK Advanced Vision Excimer laser platform (NAVEX) that allows centration based
      on surgeon specification. METHODS: Descriptive article with a case report.
      RESULTS: The software allows specification via numeric entry of the exact
      placement of the laser tapered to the position of the visual axis or the line of
      sight. CONCLUSIONS: The ability to specify the exact location of the laser
      ablation based on pupil position is fundamental in patients undergoing custom
      ablation and those with eccentric fixation. A conservative treatment strategy is
      recommended for initial experience with this alignment software.

PMID- 17444101
TI  - Seeding a simple dream: do no harm.

PMID- 17444102
TI  - College of Nursing faculty selected to train U.S. Air Force personnel on suicide
      prevention.

PMID- 17444103
TI  - Patrick Hickey.

PMID- 17444104
TI  - Nurses 'eating our young'--it has a name: lateral violence.

PMID- 17444105
TI  - The Communications Doctor offers remedies for 11 things that hurt women's career
      success.

PMID- 17444107
TI  - Collaboration with your boss: strategic skills for professional nurses.

PMID- 17444106
TI  - Being a self-advocate for your professional life.

PMID- 17444108
TI  - About appropriate staffing.
AB  - Fatigue and its impact on the individual Registered Nurse is a complex and
      individual occurrence. It is, however, a safety and ethical issue. Nursing must
      work together so nurses do not feel the need to work additional hours or jobs to
      meet reasonable financial needs. Nursing must also not punish nurses that refuse
      to work overtime but accept their decision as one made with the best interests of
      the patient at heart. The question needs to be asked, "Is having a nurse working
      fatigued a greater threat to patient and nurse safety than not having anyone
      present at all? Let's make sure we put the patient's well-being first, which in
      this instance means putting our own well-beings first also.

PMID- 17444109
TI  - AHRQ issues patient safety tips for hospitals.

PMID- 17444110
TI  - Everyday ethics securing consent.

PMID- 17444111
TI  - Sylvia Denton/Royal College of Nursing.

PMID- 17444112
TI  - Nurse's testimony re 'pressure sores' admissible.

PMID- 17444113
TI  - 'Understaffing' often results in injuries to RNs.

PMID- 17444114
TI  - PA: RN's 'right to comp.' fought by employer: 'reasonable grounds' for challenge
      existed.

PMID- 17444115
TI  - Job-injured OR nurses entitled to 'pay differential'.

PMID- 17444116
TI  - [Neurobehavioral disability following traumatic brain injury: 7 cases that
      exhibited neuropsychological impairments and neuropsychiatric syndromes].
AB  - The term "higher brain dysfunction" is used to describe neurobehavioral
      disability or neuropsychological impairment in Japan. Patients with sphenoidal
      injury and diffuse axonal injury after traumatic brain injury manifest clinical
      and neuropsychological symptoms. Following closed head injury, patients exhibit a
      variety of symptoms. In this paper, the author describes neuropsychological
      dysfunctions/courses and neuropsychiatric syndromes in 7 representative cases who
      were characterized by : (1) attention deficit, (2) memory dysfunction, (3-a)
      perseveration, (3-b) dysexecutive syndrome, (4) disorders of drive and
      motivation, (5) emotional deficits, and (6) lack of ability to recognize the
      effects of his/her behavior. There are wide varieties of difficulties in
      assessment, treatment, and rehabilitation for cognitive impairment and behavioral
      disability after traumatic brain injury. Neuropsychiatrists are expected to
      participate in this field in Japan.

PMID- 17444117
TI  - [Delusional disorder in a chronic renal dialysis patient--deprivation and
      reclaiming of body and narrative].
AB  - We report a female case treated with hemodialysis over 20 years who demonstrated
      good social functioning, until she suffered from delusional disorder with
      persecutory delusions involving medical staff performing the dialysis and also
      auditory hallucinations involving them. We examined the bio-psycho-social
      invasiveness of the renal dialysis treatment, especially concerning the effects
      on the patient's self-image of her body resulting in the loss of a feeling of
      unity between her mind and body, or the sense of her body belonging to her,
      referring to J. Lacan's concept of "corps imaginaire= imaginary body". We
      supposed the situation of "body deprivation" on the ground of the patient's
      behavior when she developed persecutory delusions that the medical staff were
      trying to deprive her of her ideal body. In this case, her persecutory delusions
      should be regarded as a reclaim for her right not to be deprived of her self
      body. We pointed out the general situation which the hegemony of modern medicine
      over patients brings about, where patients are deprived of chances to express
      their personal feelings about their illness and be listened to attentively by
      medical staffs. We recognized such a situation in the present patient and
      described the situation as "narrative deprivation". Her delusions seemed to have
      the aspect of the claim for her rebelling against the narrative deprivation. We
      emphasized the role of psychiatric staff to confirm the existence of the body
      narrative deprivation situation on the side of the patient and listen attentively
      to the patient's personal narrative of illness in the practice of consultation
      liaison psychiatry, especially when performing therapy in patients with
      persecutory delusions involving medical staff.

PMID- 17444118
TI  - [Anti-tuberculosis drug resistance survey in Japan, 2002: external quality
      assessment of results].
AB  - OBJECTIVE: A nationwide anti-tuberculosis drug resistance survey for
      Mycobacterium tuberculosis was conducted by the Tuberculosis Research Committee
      (Ryoken) in Japan, 2002, to clarify the recent trend of drug resistant M.
      tuberculosis. The drug susceptibility testing (DST) results by participating
      laboratories were compared with the test results by the reference laboratory, in
      order to evaluate the quality of DST by the participating laboratories. METHOD:
      Mycobacterium strains were collected from patients who were admitted to the 99
      participating hospitals between June and November in 2002. For each isolate, DST
      was performed at participating facilities and also at the reference laboratory
      (Research Institute of Tuberculosis: RIT) for four first-line anti-tuberculosis
      drugs, i.e., isoniazid (INH), rifampicin (RFP), streptomycin (SM) and ethambutol
      (EB). Each participating laboratory performed the DST with its routine method.
      The DST method for M. tuberculosis performed at the reference laboratory was the
      simplified proportion method on the standard 1% Ogawa medium as described in the
      national guidelines, and the results were regarded as the judicial ones. The DST
      results of each isolate from the participating laboratories were compared with
      the judicial results from the reference laboratory. The accuracy of DST done by
      the participating laboratories was evaluated in terms of the following indices;
      sensitivity for detecting drug resistant strains, the specificity for susceptible
      strain, the overall agreement, and kappa coefficient were calculated to evaluate
      the performance of local laboratories. RESULTS: A total of 3,122 M. tuberculosis
      strains were obtained out of 4,134 mycobacterial strains collected from the
      participating facilities. Fifty, 23 and 17 local laboratories used Bitspectre-SR
      (Kyokuto pharmaceuticals), Welpack S (Nichibi) and Ogawa media for DST,
      respectively. MGIT (Becton Dickinson) and BrothMIC MTB-I (Kyokuto
      pharmaceuticals) were used in four laboratories each. The sensitivity,
      specificity, efficiency and kappa coefficient for INH were 84.5%, 98.7%, 98.0%,
      and 0.798, respectively. Similarly for RFP, they were 90.3%, 99.7%, 99.5%, and
      0.894, respectively. False susceptible results were frequently observed (2.1%)
      for SM compared with false resistance (0.5%), whereas the efficiency of SM was
      97.4%. Similarly for EB, false resistances were frequently observed (2.6%)
      compared with false susceptibles (0.4%), whereas the efficiency of EB was 96.9%.
      The kappa coefficient for EB (0.470) was obviously lower than the others. The DST
      results with Ogawa method at local laboratories showed significantly lower
      sensitivity than those with Welpack S and MGIT. DISCUSSION: The DST methods used
      at local laboratories were still mainly microtitre methods with egg-based solid
      media, but the number of laboratories using liquid DST methods increased in 2002
      compared to 1997. The overall specificity and efficiency of DST for each anti
      tuberculosis drug was over 95%, but the sensitivity was below 90.3%. Because of
      the frequency of drug resistance (up to 7.9% for SM in 2002), the efficiency and
      specificity may not be useful indicators for the quality assessment. The kappa
      coefficient for the agreement between local and reference laboratories DST was
      clearly low in the case of EB, except for the laboratories using MGIT where kappa
      coefficient was higher than 0.8. The quality improvement of DST for EB could be
      achieved through the standardisation and automatisation.

PMID- 17444119
TI  - [Evaluation of accuracy of clinical diagnosis of TB by annual autopsy report].
AB  - PURPOSE: To investigate the accuracy of clinical diagnosis of TB in Japan in
      recent years and to compare them with previous studies. METHOD: Data (sex, age,
      clinical diagnosis, pathological diagnosis as cause of death) on deceased cases
      clinically or pathologically diagnosed ante mortem as having tuberculosis was
      collected from annual reports of the pathological autopsy cases in 1984, 1989,
      1994, and 1999-2004. Information on TB death from population statistics in those
      9 years also was collected and compared with data of autopsied cases. RESULT:
      Autopsy rate in these years was stably around 10 %. Comparison of gender ratio
      and mean age between the two surveys showed similar numbers. During 1999-2004,
      1725 death cases were diagnosed as TB clinically or pathologically. Number of
      pathologically proven pulmonary TB cases was 429 and that of miliary TB was 283.
      55.7% of pulmonary tuberculosis and only 21.9% of miliary tuberculosis were
      correctly diagnosed before death. Out of 156 cases clinically diagnosed as non-TB
      diseases but proven as TB pathologically, 30.8% of clinical diagnosis was
      pneumonia and/or bronchitis, followed by diagnoses of interstitial pneumonia,
      respiratory failure, pneumoconiosis and lung cancer. However, the main clinical
      diagnoses of 175 miss-diagnosed miliary TB cases were diseases other than
      pulmonary diseases such as renal failure, malignant diseases and sepsis.
      CONCLUSION: In order to reduce undiagnosed pulmonary TB cases and to prevent
      nosocomial TB infection, differential diagnosis among pneumonia and/or bronchitis
      cases should be done. In case of miliary TB, not only pneumonia but also diseases
      other than pulmonary diseases such as renal failure, malignant diseases and
      sepsis should be included in the list differential diagnosis.

PMID- 17444120
TI  - [15 cases of pulmonary Mycobacterium scrofulaceum infection].
AB  - OBJECTIVES: We described clinical features of pulmonary Mycobacterium scofulaceum
      disease. MATERIALS AND METHODS: We described 15 cases of pulmonary Mycobacterium
      scrofulaceum infection admitted to National Hospital Organization Omuta National
      Hospital from 1989 to 2003 and reviewed the clinical feature, the findings of
      chest radiograph, and clinical course. RESULTS: Sex ratio was 8 male cases and 7
      female cases, and the average age was 65.9 years old. Smoking history was found
      in 8 patients and occupational history of the dust inhalation was found in 7
      patients with pulmonary M. scrofulaceum infection. There were 11 cases of
      tuberculosis-like form and 4 cases of nodular-bronchiectasis form according to
      the NTM Research society classification based on the findings of chest
      radiography. Improvement of the findings of chest radiography was seen in 4
      patients by therapy, while no change or aggravation in 11 patients. Five patients
      died and among them, 3 died due to aggravation of pulmonary M. scrofulaceum
      infection. DISCUSSION: Cases showing tuberculosis-like form were dominant, and
      most of them showed extensive lesions when they were diagnosed, and these facts
      were considered to be major factors of difficulty in the treatment of this
      infection. The facts that 7 cases had occupational exposure to the dust,
      obstructive pulmonary disease in 3 cases, and 6 cases showed sputum culture
      positive for other nontuberculous mycobacteriosis, suggest that local resistance
      of lung might be attenuated, and this could be one of factors of onset and
      development of this infection. Only 4 cases showed improvement, while 5 cases
      died (primary disease death in 3 cases) and it was thought that the prognosis of
      the disease was in general poor.

PMID- 17444121
TI  - [Survey on nosocomial infection of tuberculosis in nursing homes for elderly in
      Osaka City].
AB  - PURPOSE: To ascertain tuberculosis (TB) infection control measures and incidence
      of TB in nursing homes for elder. SUBJECTS AND METHOD: The questionnaire on TB
      infection control was distributed to all nursing homes in Osaka City in 2005.
      RESULTS: The questionnaire was returned from 197 (90%) out of 219 facilities. In
      more than half of facilities, infection control committee was organized (57%) and
      automated ventilation system was installed (59%). In almost all facilities,
      residents had annual chest X-ray screening (94%). Respiratory symptoms were
      checked for residents and "day service" users in majority of facilities. 100% of
      employees had annual chest X-ray screening. However TB education session for
      employees was held annually in only 40% of facilities. Education materials on TB
      were distributed in 19%. Tuberculin skin test (TST) was conducted for new
      employees in 31%. TB patients were diagnosed in 22% of facilities in the past 3
      years from 2002 to 2004. Incidence rate of TB is 75.2 per 100,000 for residents
      and 24.1 per 100,000 for employees. Analysis showed that TB incidence rate is
      higher in facilities with larger number of residents and in facilities where
      infection control committee is organized, and facilities where TST is conducted
      for new employees. DISCUSSION: In Osaka City, TB infection control was more often
      implemented in facilities where TB patient was diagnosed. When age structure is
      taken into consideration, TB incidence rate of employees or residents was lower
      than general population. Nosocomial TB infection does not seem to be occurring in
      nursing homes. However, as TB patients were diagnosed occasionally, TB infection
      control measures should be strengthened in Osaka City.

PMID- 17444122
TI  - [Case of liver tuberculosis requiring differentiation from liver metastasis of
      cancer].
AB  - A 79-year-old woman was admitted to our hospital because of general fatigue.
      Chest radiograph and computed tomograph showed bronchiectasis and centrilobular
      nodules in the right middle lobe and lingula, which had not changed from previous
      examination. Intrahepatic nodular lesions and swelling of the left cervical lymph
      nodes, supraclavicular lymph node, abdominal paraaortic lymph nodes and inguinal
      lymph nodes was observed. Biopsy specimen of the liver lesion demonstrated
      epithelioid cell granulomas. Biopsy of the right inguinal lymph node demonstrated
      epithelioid cell granulomas with caseous necrosis and culture of the specimen
      showed Mycobacterium tuberculosis. The patient was diagnosed as having liver
      tuberculosis and multiple tuberculous lymphadenitis. Antituberculous treatment
      with isoniazid, rifampicin, ethambutol and pyrazinamide were started and
      continued for 6 months. All lesions improved after treatment. This was a rare
      case of liver tuberculosis that was difficult to distinguish from liver
      metastasis of cancer.

PMID- 17444123
TI  - [Case of pulmonary Mycobacterium mageritense infection: the difficulty of
      differential diagnosis of granulomatous lung diseases].
AB  - A 36 year-old female was pointed out of pulmonary abnormal shadows in the annual
      chest survey. Chest radiograph and computed tomography (CT) disclosed bilateral
      diffuse infiltrative shadows and tree-in-bud appearance in the right upper lung
      field and the left lingula. A sputum smear for acid-fast bacilli was negative.
      Histopathologically, the transbronchial lung biopsy specimen revealed non-caseous
      epithelioid granulomas with numerous giant cells. Acid-fast bacilli were cultured
      from her sputum, however, nontuberculous mycobacteria was not detected by DNA-DNA
      hybridization method. Mycobacterium mageritense was identified by 16S ribosomal
      RNA sequencing with 100% matching. The isolated colony of M. mageritense was
      resistant to nine anti-tuberculous drugs. Follow-up chest CT scan showed a
      gradual decrease of infiltrative shadows without therapy. To the best of our
      knowledge, M. mageritense infections are rare, and this is the first case report
      of pulmonary infection in the literature. We conclude that the pulmonary
      infection of M. mageritense is one of causes of granuloma formation, and in some
      case it is difficult to differentiate clinically from sarcoidosis.

PMID- 17444124
TI  - [Perspective of pulmonary MAC infection treatment].
AB  - Chemotherapy of pulmonary MAC (Mycobacterium avium complex) infection has been
      almost universally agreed with the multidrugs regimen that contains
      Clarithromycin (CAM), Rifampin (RFP), Ethambtol (EB), and aminoglycoside in case
      of advanced stage. One of the reason for the multidrugs regimen which is similar
      to tuberculous chemotherapy is to inhibit the emersion of resistant MAC strain.
      The other reasons, enhancement of anti microbial activity and response to
      polyclonal infection are unique to the MAC chemotherapy. In the current MAC
      chemotherapy, both CAM and aminoglycoside are main axes because only they can
      suppress the growth of MAC alone respectively. Efficacy of CAM was revealed
      through the randomized controlled trials of disseminated MAC infection with HIV
      and that consequences applied to pulmonary MAC infection treatment. CAM is not
      effective unless exceed 2 microg/ml blood concentration. RFP decreases CAM blood
      concentration remarkably, but the regimens contained RFP and CAM are superior
      clinically to the regimens without RFP. There seemed to be unknown
      pharmacological mechanisms with RFP. Although the advantage of aminoglycosides is
      easily achieved high blood concentration, if aminoglycoside dosage is exceed 15
      mg/kg, the possibility of auditory disturbance increase. About the duration of
      MAC chemotherapy, many guidelines recommended that one year continuation after
      the negative conversion of sputum culture. It is not the evidence but an expert
      opinion. We often experience recurrences several months later after the all drugs
      are ceased. The interval days to positive conversion of sputum culture from the
      day of completion of chemotherapy are randomly distributed with weibull's
      equation. It suggests that exogenous re-infection may cause the recurrence of
      pulmonary MAC infection as pointed out by Wallace Jr. Considering these issues,
      we have the conception of pulmonary MAC infection chemotherapy as follows. 1.
      Full dose induction chemotherapy (two years). 2. Maintenance chemotherapy (one
      year). 3. Preventive chemotherapy (one year). These conceptions have to be the
      problem validated. However, these current chemotherapies are not effective
      adequately, we need the combination treatment with surgical resection when
      indicated as a localized focus for example. Generally chemotherapy could not
      cured the destructed bronchial lesion due to MAC infection as like as local
      bronchiectasis or cavities. Consequently, the chemotherapy just after the
      surgical resection of destructed focus is most appropriate period.

PMID- 17444125
TI  - [Preventive measures against tuberculosis in working facilities and companies].
AB  - The health care program in working facilities and companies have played a
      significant part in prevention of tuberculosis. However, the ordinary national
      tuberculosis survey policy was abolished in April, 2005 and the tuberculosis
      survey for salary-earners is on the brink of drastic change. In this symposium
      the current status of the prevailing survey of tuberculosis in working facilities
      and companies was reviewed and the future direction of the tuberculosis survey in
      comparison to that in lung cancer survey was discussed. 1. Epidemiological trends
      of tuberculosis from the tuberculosis surveillance data: Masako OHMORI (Research
      Institute of Tuberculosis, Japan Anti-Tuberculosis Association). The estimated
      rate of tuberculosis case discovery by periodical mass screening in the working
      facilities was 0.033% and it was higher than that in general adult population.
      The detection rate of tuberculosis in nurses who suffered from tuberculosis
      reached 40.4% by an aid of mass X-ray screening and 8.7% by contact tracing. The
      risk of onset of the disease was 4.3 times higher nurses than in general at the
      same years of age. The importance of infection control measures in the medical
      facilities was emphasized. 2. Current status and problems in tuberculosis control
      in a large-sized company: Yusuke NAKAOKA (Department of Occupational Health,
      Osaka Railway Hospital, West Japan Railway Company). Some preventive modalities
      against TB such as periodical medical check-up and awareness programs have been
      done for the purpose of prevention in our company. The prevalence of the disease
      has significantly reduced in number. The specific circumstances in large-sized
      company should be taken into consideration, and it is important for company
      workers and health professionals to recognize their roles in preventing the
      infectious disease. 3. Are there any differences between clinical cases and
      control people working for small-sized companies in the onset of tuberculosis?:
      Osamu NAKASHIMA, Kohei IMOTO (Taito Health Center, Tokyo) and Toru MORI (Research
      Institute of Tuberculosis, JATA). We surveyed environmental conditions in working
      places and domestic conditions of employees who were working for small-sized
      companies located in Taito ward, based on written questionnaires. The companies
      were selected as those which had the patients of tuberculosis in the past one
      year period, and the number of employees was less than ten. Compared with control
      people, TB patients had more frequent smoking habit (p < 0.05), and tended to
      have been less exposed to the sunshine at their residency and to have
      nutritionally poor meals and deficits of their meals. These results suggest that
      these factors alone or in combination may contribute to accelerated onset of
      tuberculosis. 4. Current status and problems in tuberculosis management among
      high prevalence population and in health check-up for personnel with unspecified
      and high occupational contact with tuberculosis patients: Hidetoshi IGARI
      (Division of Control and Treatment of Infectious Diseases, Chiba University
      Hospital), Kiminori SUZUKI (Chiba Foundation for Health Promotion and Disease
      Prevention). Tuberculosis prevalence is as high as 500-1500 per 100,000 peoples
      among the homeless and construction workers living in "Hanba", a bunkhouse. We
      surveyed their medical conditions through periodical or extraperiodical health
      check-up. We retrospectively analyzed some medical factors contributing to
      successful treatment of the disease. Hospital admission and enhancement of
      counseling opportunities were two factors leading to the success of the
      treatment. The ambulance attendants have a significant possibility to contact
      patients with TB and are high at risk of acquiring the infection. As there are
      often limited information on TB in patients in an emergency condition, it is
      difficult to protect themselves from its contagion properly. Periodical and
      extraperiodical health check-up is important for these personnel and application
      of QuantiFERON-TB 2nd generation to the personnel is new and useful for diagnosis
      of the latent tuberculosis infection. 5. A role of chest X-ray examination for
      lung cancer detection among company workers: Takeo TESHIMA (Koseikan Clinic,
      Miyagi Branch, Japan Anti-Tuberculosis Association). Detection rates of lung
      cancer in company workers and in general population under the age of 60 years
      were compared. Chest X-ray survey was done using 10 cm x 10 cm indirect chest X
      ray films of the chest. The detection rates of lung cancer in patients with
      definite or suspicious diagnosis in 265,620 company workers were 2.3 and 2.6 per
      100,000, respectively. On the other hand the rates were 9.9 and 8.8 per 100,000
      in a general population of 811,391. Twenty-four percent of patients with
      suspicious diagnosis were eventually made a definite diagnosis. The corrected
      detection rate reached to 21.0 for male patients and 8.3 for female patients and
      12.1 totally. The detection rates of lung cancer in company workers and in
      general population under the age of 60 years exceeded the rate of pulmonary
      tuberculosis. Chest X-ray examination for the detection of lung cancer and
      pulmonary tuberculosis is still recommended under various working and social
      circumstances.

PMID- 17444126
TI  - [Improvement of routine works and quality control in mycobacterial laboratory].
AB  - Many new methods have been introduced into routine laboratory works in
      microbiology since 1990. Molecular biology, in particular, opened a new era and
      promoted a technician's skill much. PCR and hybridization technique have been
      ordinary one in many laboratories. Since old techniques such as smear and culture
      are still needed, amount of routine works is increasing gradually. Thus,
      improving efficiency and keeping quality of routine works are becoming more and
      more important issues. This symposium focused on such points, and four skilled
      technicians around Japan presented their own tips. 1. Coexistence of M.
      tuberculosis and M. avium complex (MAC) in the MGIT culture system: Yasushi
      WATANABE (Clinical Laboratory Division, NHO Nishi-Niigata Chuo National
      Hospital). Sputum samples of some tuberculosis patients yielded only MAC in the
      MGIT culture system. Such co-infected cases presented problems to mislead proper
      treatment and infection control. The detection rate of MAC was significantly
      high, and the growth speed of MAC was significantly rapid in the MGIT culture
      system, compared to those of M. tuberculosis. Additionally, M. tuberculosis was
      not detected with even more quantity than MAC in the small amount of mixed
      samples. Higher sensitivity and growth speed of MAC are the important
      characteristics of the MGIT system. 2. Internal quality control with ordinary
      examination results: Akio AONO (Department of Clinical Examination, Double-Barred
      Cross Hospital, Japan Anti-Tuberculosis Association). Our laboratory utilizes
      ordinary examination results as the internal quality control for specimen
      pretreatment, culture, and drug susceptibility testing. The contamination rate of
      MGIT culture system is useful for the evaluation of the decontamination process.
      It was 6.3% on average in our laboratory in 2005. The number of drug resistant
      strains is also useful to assess the performance of drug susceptibility testing.
      The incidence of each anti-tuberculosis drug resistance detected monthly in 2005
      is up to 5 for isoniazid (INH), 4 for rifampicin (RFP), 7 for streptomycin (SM),
      1 for ethambutol (EB), and 2 for pyrazinamide (PZA), respectively. If any serious
      deviation from the average number is observed, action for the investigation is
      taken. The analysis of the ordinary examination data is useful to implement a
      quality control efficiently, and to improve the total laboratory performance. 3.
      The advanced devices for solving problems of the smears and cultivation of
      Mycobacteria: Motohisa TOMITA (NHO Kinki-chuo Chest Medical Center). Recently,
      the newly developed, standardized, commercially available kits including PCR and
      liquid media for confirmation and identification of mycobacteria are prevalent in
      Japan for the rapid diagnosis of M. tuberculosis. These tests are sensitive and
      accurate, but still expensive and technically demanding. The improvement of these
      methods, in particular, requires time-consuming process. We have optimized the
      culture technique, the identification method, and the drug-susceptibility testing
      for Mycobacteria in a time-saving manner. They should provide a basic grounding
      in the application of the techniques for anyone who is interested in these
      intriguing bacteria. 4. Ultimate quality control of specimens--teaching how to
      get a good sputum sample: Takeshi HIGUCHI (Kyoto University Hospital). Modern
      techniques including molecular biology have been applied to routine laboratory
      works for rapid detection, identification, and drug susceptibility testing of
      mycobacteria. Even in using such techniques, however, poor quality specimens
      yield only poor results. To get a high quality specimen, particularly sputum
      samples, is very important. Therefore, laboratory technicians in our hospital
      have directly taught each patient how to expectorate good quality sputa since
      2001. The teaching of patients has improved the rate of P1 samples from 21.5% to
      36.6% by Miller and Jones visual score of sputum. The teaching has also improved
      the rate of smear positive P1 samples from 11.4% to 28.8%. To teach each patient
      how to get good sputa seems useful for keeping the laboratory quality high.

PMID- 17444127
TI  - [Destructive and protective factors in the development of tooth-wear].
AB  - The experience of the past decade proves that tooth wear occurs in an increasing
      number of cases in general dental practice. Tooth wear may have physical
      (abrasion and attrition) and/or chemical (erosion) origin. The primary physical
      causes are inadequate dental hygienic activities, bad oral habits or occupational
      harm. As for dental erosion, it is accelerated by the highly erosive foods and
      drinks produced and sold in the past decades, and the number of cases is also
      boosted by the fact that bulimia, anorexia nervosa and gastro-oesophageal reflux
      disease prevalence have become more common. The most important defensive factor
      against tooth wear is saliva, which protects teeth from the effect of acids.
      Tertiary dentin formation plays an important role in the protection of the pulp.
      Ideally, destructive and protective factors are in balance. Both an increase in
      the destructive forces, and the insufficiency of defense factors result in the
      disturbance of the equilibrium. This results in tooth-wear, which means an
      irreversible loss of dental hard tissue. The rehabilitation of the lost tooth
      material is often very difficult, irrespectively of whether it is needed because
      of functional or esthetic causes. For that reason, the dentist should carry out
      primary and secondary dental care and prevention more often, i.e. dental recall
      is indispensable every 4-6 months.

PMID- 17444128
TI  - [Immediate implant loading using DenTi implants--our long-term experience. Part
      2: Experience with DenTi implants as reflected in the literature].
AB  - Immediate loading of dental implants have been widely used to retain and support
      cross-arch partial dentures. 3-6 months after implantation the osseointegration
      is established. This period may be shortened with immediate loading of implants.
      The purpose of this study was to compare the long term experience of immediate
      loading of DenTi implants and the results reported in available literature. The
      most relevant articles were selected from current available literature. The
      influencing factors of success of immediate loading (surgery,- host,- implant and
      occlusion-related factors) were investigated and discussed in this article. The
      result of the evaluation showed that the success rate of the immediate loaded
      DenTi implants with large grit sandblasted treatment and acid etched surface was
      higher than 95 %. The success rate of the immediate loaded DenTi implants is
      similar to the ones reported in the available literature.

PMID- 17444129
TI  - [Removal of fixed partial dentures without destruction, our experience with the
      KaVo CORONAflex crown removing instrument].
AB  - Removal of fixed, cemented restorations is a great challenge for dental
      practitioner in the everyday activity. After all, prosthodontic textbooks cover
      only briefly the destructive methods of fixed restoration's removal and does not
      deal with other techniques. In many cases--i.e. at fracture of porcelain that can
      not be repaired in the mouth, or loosening of one anchor in a multi-unit
      bridgework--it would be necessary to remove the bridge without destruction. Only
      few literature data is available on this topic. From 1998 we have made an attempt
      with the KaVo CORONAflex instrument to remove various types of fixed restorations
      without destruction. The indication of removal, the material of the bridge,
      location of abutment teeth in the dental arch and success of the removal were
      documented in each cases. From the 81 fixed prostheses 61 were successfully
      removed without any destruction. Sixty two of the restorations were porcelain
      fused to metal; 19 of them were cast restorations with acrylic resin facing
      (single crowns or bridges). In most of the cases the removal of the fixed
      prostheses was successful without any damage, and consequently remaking of the
      restorations was not necessary. In this way the additional stresses associated
      with the patients' dental treatment could be avoided and also time and dental as
      well as laboratory fees could be spared.

PMID- 17444130
TI  - [Dental erosion and gastro-esophageal reflux disease].
AB  - The prevalence of gastro-esophageal reflux disease (GERD), as well as that of
      dental erosion (DE), increases steeply in the 21th century societies of Europe
      and North America. GERD is a multicausal disease, with genetic, anatomical and
      neurological insufficiencies in the background, complemented with behavioral
      factors. In GERD, as reflux occurs more often and lasts longer than
      physiologically, the result is esophagitis and supraesophageal manifestations.
      The acid, which might even reach the mouth, interacts with the material of the
      teeth and demineralization, a form of dental erosion takes place. Clinical
      studies have proved, that in patients suffering from GERD dental erosion takes
      place significantly more often than in patients who do not. It was also confirmed
      that in patients with idiopathic dental erosion GERD is significantly more
      frequent than in the "uneroded" population. These data suggest that in case of
      extended dental erosion the dentist should think of a - possibly not yet
      diagnosed - gastroenterological disease.

PMID- 17444131
TI  - [Predicting of growth tendency with cephalometry. Cephalometric research
      comparing orthodontic treatment cases with four premolar extraction].
AB  - The Hasund cephalometry gives important information about the position of the
      mandible and maxilla to each other and to the cranium in horizontal and vertical
      plane, and about the expecting mandibular growth. The aim of the study was to
      examine the reliability of the Hasund growth analysis on the basis of
      cephalogramms. The data of eighteen children having been treated with four
      premolar extraction in the growing period were compared. At the start of
      treatments the children's average age was 10 (8.5-11.5) years. Figures from the
      cephalometry were analysed by an orthodontic diagnostic program. According to our
      results the predicted growth was justified in 14 cases and contrary mandibular
      development was found in 4 cases. Beyond the limits of this study we concluded
      that the Hasund growth analysis gives mainly a reliable prognosis on predicting
      mandibular development. In diagnostic procedures this analysis should be followed
      for a successful decision-making in treatment plan. However, during the
      orthodontic treatment the prognostic results have to be monitored by using
      further cephalometric evaluations in a time-scales of a year.

PMID- 17444132
TI  - [Orthodontic and oral surgery therapy in cleidocranial dysplasia].
AB  - A cleidocranial dysplasia is an autosomal dominant inherited condition consisting
      of generalized skeletal disorder. Associated dental signs are present in 93,5%;
      failure of tooth eruption with multiple supernumerary teeth, dilaceration of
      roots, crown germination, microdontia, high arched palate, midface hypoplasia,
      high gonion angle. The molecular- genetic analysis revealed a missense mutation
      in the CBFA1 gene located on chromosome 6p21, which is considered to be
      etiological factor for CCD. Orthodontic and oral surgery therapy of a 13 year-old
      child with CCD was performed due to aesthetic and functional problems. The
      supernumerary germs were removed and the teeth were aligned with orthodontic
      appliances. Temporary functional rehabilitation was solved with partial denture.
      The presented case and the literature data support the importance of early
      diagnosis of CCD. The good collaboration of the orthodontic and maxillo-facial
      surgery specialists help achieve the correct rehabilitation of the patient.

PMID- 17444133
TI  - [Report of a rare case of temporomandibular ankylosis as a result of rheumatoid
      arthritis].
AB  - The case and surgical treatment of a patient with rheumatoid arthritis causing
      bony ankylosis of the temporomandibular joint are presented. The main
      characteristics of polyarthritis are also surveyed.

PMID- 17444134
TI  - [Synthesis and compression strength of hydrogels].
AB  - The purpose of the present investigation was the synthesis of crosslinked
      polymers and the assay of the effect of the monomer ratio to the compression
      values. Hydrogels were made by free radical photoinitiation from 2-hydroxyethyl
      metachrylate (HEMA) monomer, poly(ethylene glycol) dimethacrylate (PEG-DMA)
      crosslinker and sodium anthraquinone-2-sulphonate initiatior. The concentration
      of HEMA and PEG-DMA was 30 %, and their ratio was varied to obtain gels with
      different crosslinking density. It was found, that increasing the amount of the
      crosslinker in the gels, the force of the deformation increased, however the
      elasticity decreased. The lowest difference was found between the molar ratio of
      50% HEMA: 50% PEG-DMA and the 75% HEMA: 25% PEG-DMA gels. Compression strength
      was strongly influenced on the ratio of the crosslinking agent. The smallest
      compression strength was found at the lowest amount of PEG-DMA (90% HEMA: 10% PEG
      DMA) (0.0475 MPa +/- 0.0117) and the highest value was found at the highest
      amount of the PEG-DMA (10% HEMA: 90% PEG-DMA) (0.1366 MPa +/- 0.0546). The values
      of the compression strength at gels with similar composition was not
      significantly different. On the base of the present investigations the elasticity
      of the materials could be calculated from the ratio of monomers. It could be an
      important parameter in the further applications of the gels as a local delivery
      system in the parodontology.

PMID- 17444135
TI  - [Determination of working length in general endodontic practice].
AB  - Accurate determination of root canal length is essential for successful
      endodontic therapy. Two methods are generally accepted for working length
      measurements: radiographic length determination and by the means of electronic
      apex locators. The purpose of this study was to evaluate the working length
      determination habits of Hungarian dentists using a survey form containing 15
      selective closed questions for data collection. The results indicate that 70% of
      the dentists preferred the radiographic method. 19% of the responders employ
      electronic apex locator. 21% of dentists relied on fingertip tactile sense or on
      the patient's response. 44% of the responders determined the working length after
      pulp tissue removal. 22% of dentists make the measurements at the end of root
      canal instrumentation. 34% of the dentists disregard the evaluation of the
      preoperative radiographs for the estimated working length determination. The
      results suggest that whilst most of the general practitioners use the techniques
      currently taught in dental schools, a large proportion of them apply methods not
      accepted by contemporary dental profession.

PMID- 17444136
TI  - Correlation between exercise electrocardiography test and coronary flow reserve
      in patients without organic coronary artery stenosis.
AB  - OBJECTIVES: The exercise electrocardiography (ECG) test is frequently positive in
      patients without organic coronary artery stenosis. Although the reason for this
      false positive ST depression is not fully understood, one possibility may be
      related to coronary microvascular abnormality. The present study investigated the
      relationship between the exercise ECG test and coronary flow reserve (CFR) in
      patients with angiographically normal coronary arteries, but with positive ECG ST
      depression. METHODS: This study included 67 patients, 32 with chest pain
      syndrome, and 35 with vasospasm. The exercise ECG test was performed without drug
      administration in all patients, and the CFR was determined after diagnostic
      cardiac catheterization. RESULTS: Although a significant correlation was
      recognized between ST depression and CFR in patients with chest pain syndrome (p
      < 0.05), there was no correlation in patients with epicardial coronary vasospasm.
      CONCLUSIONS: In patients with chest pain syndrome, ST depression detected by the
      exercise ECG test may suggest coronary microvascular dysfunction. However, in
      patients with coronary vasospasm, ST depression may occur without decreased CFR,
      suggesting that coronary spasm or other mechanism (s) relating to ST changes are
      present during the exercise ECG test, and careful interpretation is needed.

PMID- 17444137
TI  - Impact of statin therapy on coronary intervention for non-ST elevation acute
      coronary syndrome with decreased low-density lipoprotein cholesterol.
AB  - OBJECTIVES: The benefits of treating patients with acute coronary syndrome (ACS)
      with statins are well established. This study investigated the effects of statins
      on patients who presented with low levels of low-density lipoprotein (LDL)
      cholesterol, were diagnosed with non-ST elevation ACS, and subsequently underwent
      percutaneous coronary interventions (PCI). METHODS: From 2000 to 2003, 87
      patients(mean age 68 +/- 10 years, 69 males, 18 females) underwent PCI because of
      non-ST elevation ACS, and had low LDL cholesterol on presentation. These patients
      were divided into two groups: those who had been taking statins (S-group, n =
      46), and those not taking statins, or controls (C-group, n = 41). Only patients
      whose LDL cholesterol was < 100 mg/dl at admission (average: 82 +/- 12 mg/dl)
      were included in the study. Troponin-T (TnT), creatine kinase (CK), CK-MB, and
      high-sense C reactive protein (hs-CRP) were measured before and 6 hr after PCI.
      The two groups were evaluated at 6 months clinical follow-up. RESULTS: There was
      no difference in these markers before PCI in both groups. TnT and CK-MB in the S
      group at 6 hr post-PCI were significantly decreased compared to those of the C
      group (0.45 +/- 1.34 vs 1.40 +/- 2.37 ng/ml, respectively, for TnT, p = 0.04;
      17.2 +/- 45.5 vs 81.3 +/- 157.2 IU/l, respectively, for CK-MB, p = 0.02). Major
      adverse cardiac events (MACE) defined as death, myocardial infarction, congestive
      heart failure and target lesion revascularization were evaluated after 6 months.
      There was no difference in MACE between the two groups. CONCLUSIONS: Statin
      treatment before PCI in patients with non-ST elevation ACS demonstrated
      beneficial effects such as less myocardial damage, even though both groups
      presented with low LDL cholesterol levels. However, no significant effect on MACE
      was seen at 6 months after PCI.

PMID- 17444138
TI  - [Left ventricular volume and ejection fraction by the axius auto ejection
      fraction method: comparison with manual trace method and visual assessment of
      ejection fraction].
AB  - OBJECTIVES: Visual assessment of the ejection fraction (EF) is often used in
      clinical practice, but is subjective and requires training and experience. The
      auto EF method has been newly developed for automated detection of the left
      ventricular (LV) endocardial border throughout the cardiac cycle. The clinical
      feasibility was assessed of the auto EF method for measuring LV volumes and EF in
      patients. Manually traced EF measured by the biplane modified Simpson's rule was
      used as the reference standard. METHODS: The study population consisted of 30
      consecutive patients with normal sinus rhythm. All patients underwent two
      dimensional echocardiography. The auto EF method incorporated pattern and shape
      recognition to automatically locate the LV, track the endocardium, and calculate
      EF from routine digital images. LV end-diastolic and end-systolic volumes and EF
      measured by the auto EF method were compared those by the manually traced method.
      LVEF by the Auto EF method was also compared with visual EF determined by
      nonattending physicians. RESULTS: Auto EF was more reproducible than visual EF by
      the expert reader. LVEF by the auto EF method had excellent correlation and close
      limits of agreement with manually traced EF compared with visual EF(4-chamber
      view: y = 1.10 x - 4.28, r = 0.94, bias = 1.6%, 2-chamber view: y = 0.88 x +
      7.25, r = 0.90, bias = 0.4%). LV volumes by the auto EF method underestimated
      those by manually traced EF (end-diastolic volume by 4-chamber view: y = 0.72 x +
      8.92, r = 0.93, bias = - 16.7 ml, end-systolic volume by 4-chamber view: y = 0.82
      x - 0.97, r = 0.98, bias = - 8.5 ml, end-diastolic volume by 2-chamber view: y =
      0.73 x + 12.4, r = 0.82, bias = - 12.3 ml, end-systolic volume by 2-chamber view:
      y = 0.65 x + 6.94, r = 0.90, bias = - 6.8 ml). CONCLUSIONS: The auto EF method is
      a clinically useful tool for the measurement of LV volumes and EF.

PMID- 17444139
TI  - [Suppressive effect of nicorandil in ventricular arrhythmias after reperfusion
      therapy in patients with acute myocardial infarction].
AB  - BACKGROUND: Nicorandil is reported to inhibit reperfusion arrhythmias in patients
      with acute myocardial infarction (AMI), but few studies have counted ventricular
      arrhythmias with Holter electrocardiograms in patients treated with nicorandil
      following AMI reperfusion. OBJECTIVES: In the present study, we examined the
      effects of nicorandil by investigating the occurrence of ventricular arrhythmia
      with Holter electrocardiogram monitoring after percutaneous coronary intervention
      with acute myocardial infarction. METHODS: Forty patients with AMI who underwent
      successful percutaneous coronary intervention (PCI) were enrolled and randomly
      assigned to nicorandil or placebo groups. Following PCI, nicorandil was infused
      intravenously at 6 mg/hr for 24 hr, with Holter electrocardiogram monitoring.
      Patients with 100 or more premature ventricular contractions (PVCs) over the 24
      hour period were studied. The total number of PVCs, frequency of occurrence of
      ventricular tachycardia, and clinical characteristics were compared between the
      two groups. RESULTS: Fourteen patients in the nicorandil group and 12 patients in
      the placebo group exhibited 100 or more PVCs over the 24-hour period. Lesion
      characteristics and procedural factors did not differ between the two groups.
      Fewer PVCs were counted in the nicorandil group than in the placebo group(144.6
      +/- 106.5 vs 286.8 +/- 159.1 beats/day, p = 0.012). The frequency of coupled PVCs
      was lower in the nicorandil group (6.9 +/- 6.9 vs 16.3 +/- 12.8 beats/day, p =
      0.025). Although the frequency of ventricular tachycardia did not differ between
      the two groups, ventricular tachycardia duration was significantly shorter in the
      nicorandil group (3.73 +/- 2.30 vs 8.34 +/- 7.45 sec, p = 0.03). CONCLUSIONS: Our
      study indicates nicorandil inhibits ventricular arrhythmias following PCI for
      patients with AMI. Nicorandil treatment following PCI for AMI is convenient and
      may reduce the rate of cardiac events by inhibiting ventricular arrhythmias,
      thereby potentially improving the prognosis.

PMID- 17444140
TI  - Progressive congestive heart failure due to common iliac arteriovenous fistula: a
      case report.
AB  - Arteriovenous shunt is one of the causes of heart failure, but heart failure
      caused by common iliac arteriovenous fistula is relatively rare. A 64-year-old
      man who developed acute heart failure due to venous perforation of a common iliac
      aneurysm and also had bilateral aneurysms (diameter 58 mm) was referred to our
      department. On admission, the patient complained of dyspnea and swollen left leg,
      so diuretic agent was administered to treat the heart failure. Cardiac
      catheterization showed a shunt rate of 80.6%, as well as 5.0 Qp/Qs and O2 step-up
      across perforation of the common iliac vein. Despite the therapy, pleural
      effusion and ascites exacerbated, and the heart failure became difficult to
      control, so surgical treatment was performed. The aneurysm was replaced with an
      artificial vessel, and the fistula was closed by direct suturing.
      Postoperatively, the symptoms disappeared, and the patient is in good health.

PMID- 17444141
TI  - [Left ventricular dysfunction without brain natriuretic peptide elevation: two
      case reports].
AB  - Brain natriuretic peptide (BNP) is an useful marker for the differential
      diagnosis of dyspnea and pleural effusion of unknown origin. BNP elevation
      indicates myocardial overload. Two patients were admitted to our hospital with
      abnormal electrocardiogram or dyspnea. Left ventricular ejection fractions were
      below 40% and BNP levels were below 2.0 pg/ml in both patients. The diagnoses
      were dilated cardiomyopathy (DCM) based on coronary angiography, and pathological
      examination and suspected secretion insufficiency of BNP. Immunohistochemistry
      for BNP showed no significant difference in BNP expression in the myocardium
      between patients with DCM and elevated BNP and the present patients. We recommend
      that patients with intractable dyspnea undergo echocardiography at least once
      even if their BNP level is low.

PMID- 17444142
TI  - [Pericardial calcification identified by chest radiography].

PMID- 17444143
TI  - [Postprandial hyperglycemia is a possible contributor to paroxysmal atrial
      fibrillation: a case report].

PMID- 17444144
TI  - [Comparative analysis of modern combined methods in diagnosis of renal cell
      carcinoma].
AB  - To ascertain the role of multispiral computed tomography (MSCT) in diagnosis of
      renal cell carcinoma (RCC) and to propose optimal diagnostic policy in RCC
      patients, we examined 63 patients with suspected renal tumor: 37 (59%) males and
      26 (41%) females, age 47-77 ages, mean age 54.2+/-1.5 years, duration of the
      disease from 1 month to 7 years. The following diagnostic methods were imployed:
      ultrasonography of the kidneys, plain and excretory urography, spiral computed
      tomography, angiography, MSCT, MRT, thin-needle aspiration biopsy. By the results
      of a combined examination and operation on the kidney lesion, the diagnosis of
      RCC was made in 45 (80.3%) patients including stage I in 21 (46.7%), stage II in
      9 (20%), stage III in 13 (28.9%), stage IV in 2 (4.5%) patients. Benign renal
      tumors were detected in 8 (14.2%) patients, giant cysts of the kidneys--in 5
      cases, benign renal tumors--in 3 cases, adenoma--in 2 cases, angiomyolipoma--in 1
      case. Detected were also renal malformations in 3 cases, a distant
      retroperitoneal metastasis of RCC in 1 case, adrenal tumors in 6 (9.5%) cases. We
      suppose that MSCT enables multiplanar and 3-dimentional reconstruction of the
      images, staging of RCC, planning of surgical treatment. MSCT should be conducted
      after standard ultrasound examination.

PMID- 17444145
TI  - [Photoselective vaporization with high-performance potassium-titanil-phosphate
      laser in the treatment of obstructive prostatic adenoma].
AB  - Novel laser technologies were used in development of a new highly effective and
      simple method of laser adenomectomy (LA) called photoselective vaporization of
      the prostate (PVP). The method employs powerful radiation from the laser on the
      base of potassium titanil-phosphate crystal. Laser radiation was delivered
      transurethrally by means of a light guide with lateral luminescence. The light
      guide is installed in a small-diameter channel of the cystoscope and conducts
      rapid vaporization of adenomic tissues in good hemostasis. Numerous international
      investigations showed that this method does not provoke hemorrhages, shortens
      drainage of the urinary bladder with urethral catheter or cathetarization can be
      avoided, duration of post-operative rehabilitation of the patients, is safe in
      terms of complications. Efficacy of PVP is comparable to transurethral resection
      (TUR) of prostatic adenoma but is more cost-effective than TUR or other low
      invasive techniques. PVP is safe in patients with concomitant diseases and
      abnormal coagulation (hemophilia, anticoagulant therapy). Therefore, PVP is very
      promising in surgical treatment of obstructive prostatic adenoma and may become a
      leading surgical method in this disease.

PMID- 17444146
TI  - [New approaches to molecular diagnosis of prostatic cancer].
AB  - We compared prostatic proteins in patients operated for adenoma or cancer. 630
      protein fractions were obtained from each tissue sample after fractionation by
      two-dimentional electrophoresis according to O'Farrell. Comparison of the samples
      from adenoma and cancer showed their difference by 7 proteins among which were
      isoforms of glyceraldehydes-3-phosphate-dehydrogenase, alpha-collagen and several
      little known proteins. Most of the cancer patients had the protein with molecular
      mass 19 kDa and isoelectric point 9.0. By the results of mass-spectrometry this
      protein was identified as androgen-induced secreted protein AGR2. This protein is
      considered a potential oncomarker. Prospects of some postgenome technologies for
      detection of new diagnostic markers of prostatic cancer are discussed.

PMID- 17444147
TI  - [Appendicouretheroplasty].
AB  - Repair of long uretheral defects with the appendix (appendi-couretheroplasty-
      AUP) was made in 5 patients. Stenosis of the lumbar urether was caused by a
      gunshot wound in one patient. Uretheral strictures developed after iatrogenic
      injury during extended gynecological operations in 3 women. The strictures arose
      after radiotherapy in one female. The man has undergone plastic reconstruction of
      the upper third of the right ureter, while women - replacement of the pelvic
      urether, including one case on the left. In two cases a modified surgical
      technique was used for better appendicocystanastomosis--a flap was dissected from
      the cupola of the cecum. In one case surgery was combined with simultaneous
      contralateral Boari's operation, in the other case--with transvaginal suturing of
      the vesicovaginal fistula. Exacerbation of chronic pyelonephritis occurred in one
      patient. In the other case antegrade pyeloureterography has detected stricture of
      ureteroappendicoanastomosis. Resection of the stricted place and reanastomosing
      were performed in this patient. Passability of the urinary tract recovered in all
      the patients. Thus, replacement of any part of the right and pelvic part of the
      left ureter with the appendix is feasible with good results.

PMID- 17444148
TI  - [Choice of surgical correction of varicocele based on the characteristics of
      venous hemodynamics].
AB  - A complex ultrasound investigation of the left renal, testicular veins, those of
      the pampiniform plexus and intraoperative analysis of varicose venous truncks
      specify hemodynamic aspects of varicocele genesis, identify a group of patients
      with suspected regional venous renal hypertension and help to decide on surgical
      policy. Hemodynamic disorders leading to varicocele can be corrected with
      consideration of regional venous renal hypertension by surgical interventions
      with creation of testiculo-inferio-epigastric, testiculo-inferio-epigastric
      superficial and testiculosafic anastomoses and their combinations. Valid are
      microsurgical corrections of types I and II according to Coolsaet disorders of
      venous hemodynamics in varicocele using non-varicose testicular veins. In the
      presence of type III and/or signs of venous renal hypertension, combinations of
      venous anastomoses are practiced. The results of duplex angioscanning of the
      region of anastomoses and analysis of male fertility evidence for positive early
      and late outcomes of microsurgical treatment of varicocele.

PMID- 17444149
TI  - [The free synthetic loop in the treatment of urinary stress incontinence in
      women: comparative analysis of postoperative complications].
AB  - Operations with application of a free synthetic loop were made in 504 female
      patients with urinary stress incontinence (USI). The patients were divided into
      two groups. Patients after TVT operation, not operated with reconstruction of the
      pelvic fundus entered group 1 (n = 207). Patients after TVT-0 operations (n =
      109) entered group 2. The data were processed with the criterium chi-square,
      significance was stated in p < = 0.05. The following intra- and postoperative
      complications were registered: de novo imperative symptoms, pelvic hematoma,
      perforation of the urinary bladder. The latter complication occurred in 1 (0.48%)
      patient of group 1 and in none from group 2. Pelvic hematomas were in 2.9 and
      0.92% patients, respectively. De novo imperative symptoms were observed in 2.9
      and 1.83%, respectively. It was stated that differences in complications between
      the groups were insignificant. Further multicenter controlled randomized studies
      are necessary.

PMID- 17444150
TI  - [Resistance of causative agents of uncomplicated urinary tract infections in
      Russia].
AB  - A prospective epidemiological study of the spectrum of causative agents (CA) of
      uncomplicated urinary tract infections (UTI) in adult patients and CA resistance
      to antimicrobial drugs was conducted in nine cities of the Russian Federation in
      2004-2005. Minimum inhibiting concentrations were ascertained by dilution in agar
      according to NCCLS (2000-2002) recommendations. The study has found that
      uncomplicated UTI are most frequently caused by E.coli (73.9%). Other CA occur
      much less frequently: K.pneumoniae--6.4%, E. faecalis--4.4%, S. epidermidis-
      4.1%, Staphylococcus spp--3.4%, others--2% patients. E. coli demonstrated high
      resistance to ampicilline (33.1%), co-trimoxasol (19.4%). Most active against E.
      coli were fluoroquinolones (norfloxacin, ciprofloxacin, levofloxacine), the
      resistance being 4.8%; cefalosporins of the second and third generation
      (cefuroxim, ceftibuten), nitrofurantoin, no resistant strains were found.

PMID- 17444152
TI  - [Use of oral vitaprost in the treatment of chronic abacterial prostatitis].
AB  - An open trial performed in 2001 by the Research Institute of Urology has
      demonstrated good efficacy and safety of rectal suppositoria Vitaprost, the
      active substance of which is a complex of water-soluble biologically active
      peptides isolated from bovine prostate, in combined treatment of chronic
      bacterial and abacterial prostatitis in patients of all ages including those with
      concomitant adenoma. Current comparative clinical trial has shown that Vitaprost
      tablets in combination with nonsteroid anti-inflammatory drugs effectively treat
      prostatic inflammation in patients with chronic abacterial prostatitis, produce
      more potent and stable effect than monotherapy with ketonal. The absence of side
      effects and negative alterations in clinical and biochemical blood and urine
      parameters evidences for good tolerance and safety of Vitaprost tablets.
      Vitaprost tablets can be used in therapy of chronic abacterial prostatitis for
      raising efficacy of the standard treatment in patients of different ages and
      having associated diseases.

PMID- 17444151
TI  - [Diagnosis and treatment of urinary bladder dysfunctions in patients with
      nephrotuberculosis].
AB  - A combined, including urodynamic, study was made in 129 patients with abnormal
      reservoir function of the urinary bladder (UB). Of them, 82 patients had
      nephrotuberculosis (NT). Cystoscopy was made in 93 patients, endovesical
      multifocal biopsy of the bladder wall-- in 23. Correction was conducted with
      alpha-adrenoblocker alfusozine. In NT, sensory functional disorders of UB prevail
      (60%). The degree of fibrous-inflammatory involvement of the bladder wall by
      biopsy findings and severity of urodynamic disorders do not correlate (r < 0.03).
      Miction recovered in 81.5% patients with NT taking alfusozine. Ileocystoplasty (n
      = 20) was made in treatment failure and total UB fibrosis. Long-term pathogenic
      action of specific infection on the neuroreceptor system of the UB may cause
      defects in its activity. Complex urodynamic investigations of the lower urinary
      tracts in NT patients identify the type of the disorder and help in making choice
      of pharmacological or surgical correction. Alfusoxine is a drug of choice in UB
      hypersensitivity.

PMID- 17444153
TI  - [New aspects of efficacy of using apparatus-programming complex "andro-gin" in
      the treatment of chronic prostatitis].
AB  - The results of usage of Andro-Gin unit in 187 patients with chronic prostatitis
      have shown that in most cases prostatitis is caused by bacteria. Andro-gin unit
      included in combined treatment of chronic prostatitis provides good results as it
      turns biofil bacteria into planktonic ones.

PMID- 17444154
TI  - [Using doxasosine and finasteride combination in the treatment of prostate
      adenoma].
AB  - The study was made in 2005-2006 of efficacy and safety of combined use of
      doxasosine and finasteride in patients (n = 50, age 53-83) with symptoms of lower
      urinary tract dysfunction (LUTD) caused by prostatic adenoma. LUTD severity by
      IPSS, size of the prostate, maximal and mean urinary flow velocity, functional
      capacity of the urinary bladder, residual urine, blood pressure, a PSA level,
      sexual function, were assessed at baseline and after the treatment. Side effects
      were also registered. Combined treatment with doxasosine plus finasteride
      significantly lowered both obstructive and irritative LUTD symptoms by IPSS,
      quality of life improved from 3.4 to 2.3 scores (p < 0.01), maximal urinary flow
      and mean urinary flow velocity increased from 10.2 to 11.6 ml/s and from 5.4 to
      6.1 ml/s, respectively, residual urine reduced from 35.2 to 7.7 ml (p < 0.01).
      The size of the prostate diminished from 55.8 to 46 cm(3) (p < 0.01). PSA
      decreased from 2.8 to 1.4 ng/ml. Erectile function did not worsen. Thus, the
      proposed scheme of combined treatment improves quality of life, voiding; lowers
      residual urine; is well tolerated; can be recommended as a basic scheme of
      treatment in patients with a risk of prostatic adenoma progression.

PMID- 17444155
TI  - [Using terasosine (setegis) in the treatment of hyperactive urinary bladder in
      elderly women].
AB  - Terasosine study covered 36 females aged 61 to 76 years (mean age 70.1 +/- 0.5
      years) with hyperactive urinary bladder (HAUB). Thirty patients received alpha1
      adrenoblocker terasosine (setegis) in a dose 1 mg twice a day for 2 months, 6
      females were given placebo. At baseline, in 1 and 2 months the patients self
      estimated urination, urine incontinence, imperative voiding, quality of life,
      discomfort, treatment satisfaction. Two months of therapy reduced imperative
      voiding by 70%, number of episodes of ugent incontinence by 90%. Capacity of the
      bladder increased by 30%. The patients reported improved condition of their
      bladder, 3 times lower discomfort because of imperative symptoms, satisfaction
      with treatment reached 71%. Patients of the placebo group noticed no significant
      positive trend in the above parameters. 43% patients with maximal improvement and
      cure of urine incontinence had good long-term results.

PMID- 17444156
TI  - [Substantiation of the duration of m-cholinolytics administration in conservative
      treatment of hyperactive urinary bladder].
AB  - The analysis of treatment outcomes in 74 patients with hyperactive urinary
      bladder (HUB) has shown that duration of the treatment depends on the initial
      function of the lower urinary tracts. There was a correlation between mean
      effective therapy and treatment duration. Estimation of this correlation allows
      prognosis of treatment efficacy and selection of optimal anticholinergic drug for
      correction of miction disorders. Spasmex proved to be the most adequate drug for
      long-term treatment due to minimal number of side effects and feasibility to vary
      dose and regimen of intake.

PMID- 17444157
TI  - [Renal development long after correction of primary non-refluxing forms of
      megaureter in children].
AB  - We studied the condition and development of 50 kidneys in 45 patients 10-30 years
      after surgical correction of megaureter. We made resection and neoimplantation of
      the ureter according to the antireflux technique. By x-ray findings, we estimated
      area of the kidney, renocortical index and compared them with visual assessment
      of the condition of the kidney and its pelvicocalicyal system. We have found that
      correction of the megaureter creates favourable conditions for development of the
      kidney as shown by good growth of the kidney (area increased 1.5-3.5 fold) in a
      stable renocortical index. This indicates stabilization of nephrosclerosis and
      large area of renal parenchyma. However, kidney growth was accompanied with
      developing nephrosclerosis in 7 cases, in 1 case nephrosclerosis terminated with
      secondary contraction and a decline of renal function. The condition of the
      kidney varied due to many factors such as the condition of the immune system, age
      of the patient, virulence of the microflora, etc., but the key role for the
      kidney belonged to condition of renal parenchyma before surgical intervention.
      The data of light optic (53 cases) and electron-microscopies (3 cases)
      examinations of renal biopsies demonstrated that renal lesions were characterized
      by congenital structural disorders such as low number of nephrons, the presence
      of canalicular and glomerular microcysts and other manifestations of hypoplastic
      dysplasia. Inflammatory infiltration of the cortical and medullary layer
      interstitium aggravated severity of renal lesion. Various correlation and
      severity of congenital and aquired lesions characterized condition of the kidney
      in each individual case. Thus it is necessary to conduct a long-term follow-up
      and update methods of therapy.

PMID- 17444158
TI  - [Effects of alpha-tocopherol on partial functions of the ischemic kidney].
AB  - The experiments on 45 rats and 20 rabbits were made to investigate antiischemic
      efficacy of alpha-tocopherol in respect of various partial functions of the
      kidneys compared to its antioxidant activity. It is demonstrated that
      administration of alpha-tocopherol prior to 30-min heat ischemia arrests
      activation of membrane lipid peroxidation (LPO) in the tissue of ischemic kidney
      both in rabbits and rats. Rabbit filtration renal function 1 hour after
      circulation recovery improved insignificantly, 24 hours after the recovery no
      difference with the control was registered, while secretory and reabsorption
      functions of the renal tubules under conditions of pretreatment with alpha
      tocopherol significantly improved both in rabbits and rats both 1 hour and 24
      hours after ischemia. Estimation of Ca-ATP activity of a microsomal fraction of
      the cortical substance of the ischemic kidneys has detected alpha-tocopherol
      induced suppression of LPO in sub-cellular membrane and high activity of this
      enzyme. Mechanisms of different protective action of alpha-tocopherol on renal
      glomeruli and tubules are discussed.

PMID- 17444159
TI  - [Condition of the kidney vascularity in chronic disorder of venous blood
      outflow].
AB  - To estimate structural changes in the kidneys exposed to chronic venous
      congestion, a 65-75% stricture was made in the pulmonary trunk of 24 pups. Twelve
      dogs were controls. The animals were followed up from 6 months to 2 years. Venous
      pressure was measured, the kidneys were studied histologically, stereometrically
      and morphometrically. There was hypertension in the posterior vena cava
      reflecting chronic defects in the venous blood outflow from the kidneys. The
      capacity of the venous and arterial renal circulation was increased and reduced,
      respectively. There was some reduction of the glomerular system. Muscular
      hypertrophy of the walls of renal veins and arteries was adaptive. Pathological
      alterations in the kidneys were represented by sclerosis of the walls of the
      renal veins, connective tissue thickening of arterial intima, sclerosis and
      hyalinosis of arterioles and glomeruli, dystrophy of canalicular epithelium,
      renal parenchyma atrophy, renal stroma growth.

PMID- 17444160
TI  - [Ectopy of the accessory ureter ostium in combined anomaly of the urinary tract].

PMID- 17444161
TI  - [Infravesical obstruction in women].

PMID- 17444162
TI  - [Current views on the mechanism of photodynamic therapy. Photosensitizers and
      their bioavailability].

PMID- 17444163
TI  - [Some issues of etiology and pathogenesis of urolithiasis].

PMID- 17444164
TI  - Dawn of cardiac surgery in Japan.
AB  - Because of World War II, the development of closed heart surgery in Japan was
      delayed for several years. As far as open heart surgery was concerned, the
      tireless Japanese investigators in the early 1950s worked extremely hard to
      quickly catch up with the North Americans and Europeans. Looking back at the dawn
      of Japan's open heart surgery, we are impressed at how the investigators
      precisely reported their experiences as cited in this editorial, how many times
      they repeated their experiments prior to clinical application, and most
      importantly how cooperatively they worked as a group even in the very competitive
      environment.

PMID- 17444165
TI  - Early results of Bentall-type operations during the last 10 years: comparison of
      mechanical valves and stentless bioprostheses.
AB  - OBJECTIVE. Various types of prostheses have been used for combined diseases of
      the aortic root and ascending aorta. METHODS: All Bentall-type operations (n=64)
      between 1996 and 2005 were retrospectively studied, comparing different types of
      prosthesis in the aortic position. The patients were 29-87 years old (mean 59.5
      +/- 14.0 years) and included 47 men and 17 women. Mechanical valves, stentless
      bioprostheses (Freestyle), stented bioprostheses, and a homograft were used in
      31, 29, 3, and I patients, respectively. Early results, especially hemodynamics,
      were analyzed among two groups: mechanical valve group (M-group) and Freestyle
      group (F-group). RESULTS: The average age was significantly higher in the F-group
      (62.8 +/- 12.7 years) than in the M-group (54.9 +/- 14.0 years) (P = 0.025). The
      implanted valve was significantly larger in the F-group (26.0 +/- 2.3 mm) than in
      the M-group (23.5 +/- 2.1mm) (P = 0.000). The estimated effective orifice area of
      the prosthesis was significantly larger in the F-group (2.23 +/- 0.38 cm2) than
      in the M-group (1.84 +/- 0.49 cm2) (P = 0.001). The pressure gradient across the
      prosthesis was significantly lower in the F-group (18.6 +/- 5.5 mmHg) than in the
      M-group (25.4 +/- 7.6 mmHg) (P = 0.001). CONCLUSION: The Bentall-type procedure
      using the Freestyle valve has an advantage regarding hemodynamics compared to the
      procedure employing mechanical prostheses.

PMID- 17444166
TI  - Relationship between increased blood pressure and hematocrit during modified
      ultrafiltration for pediatric open heart surgery.
AB  - OBJECTIVE: Modified ultrafiltration increases blood pressure after
      cardiopulmonary bypass in children. To investigate the cause of this hemodynamic
      improvement, we assessed the relationship between increased blood pressure and
      hematocrit. METHODS: We retrospectively assessed 30 consecutive patients who
      underwent ventricular septal defect closure, and divided them into two groups:
      group M (modified ultrafiltration, n=15) and group C (conventional ultra
      filtration, n=15). We compared the intraoperative transitions of blood pressure
      and hematocrit, and analyzed the correlations between blood pressure and
      hematocrit at 15 min after cardiopulmonary bypass (immediately after modified
      ultrafiltration in group M) and between the percent increases in blood pressure
      and hematocrit during modified ultrafiltration. RESULTS: Although intraoperative
      central venous pressure and dopamine dosage were similar, in group M, increases
      in hematocrit (26.4% +/- 4.9% to 31.9% +/- 5.7%, P < 0.01) and systolic blood
      pressure (61.1 +/- 10.3 to 75.6 +/- 11.5 mmHg, P < 0.01) occurred during modified
      ultrafiltration. Furthermore, diastolic and mean blood pressure at 15 min after
      cardiopulmonary bypass (after modified ultrafiltration) were higher in group M
      than in group C. However, systolic, mean, and diastolic blood pressure were not
      correlated with increased hematocrit after modified ultrafiltration, and there
      was also no correlation between the percent increases in each blood pressure and
      hematocrit. CONCLUSION: Modified ultrafiltration increased blood pressure and
      hematocrit immediately after cardiopulmonary bypass in children. However, no
      correlations were detected between the increases in blood pressure and
      hematocrit. These results indicate hemoconcentration is not the major cause of
      the increased blood pressure during modified ultrafiltration.

PMID- 17444167
TI  - Right ventricular failure due to primary right ventricle osteosarcoma.
AB  - A 68-year-old woman with symptoms of dyspnea and peripheral edema was referred to
      our hospital. Chest computed tomography (CT) scans revealed a huge mass occupying
      the pulmonary trunk and invading the right main pulmonary artery, with metastatic
      nodules in the left main and left lower pulmonary artery. She was given a
      diagnosis of pulmonary thromboembolism and was anticoagulated to no effect, which
      suggested a neoplasm. Palliative resection of the tumor was carried out even
      though she was in serious condition with right ventricular failure, liver
      congestion, renal dysfunction, and coagulopathy disorder. The histopathology,
      postoperative systemic CT scan, and bone scintigram provided a definitive
      diagnosis of a primary right ventricle osteosarcoma. Primary cardiac osteosarcoma
      has a poor prognosis, and this patient was at an advanced stage with pulmonary
      metastases. Surgical intervention should offer these patients significant
      palliation to relieve the clinical symptoms due to obstruction.

PMID- 17444168
TI  - Clot formation between the folded graft layers in the reversed elephant trunk
      technique at the second stage of total arch replacement.
AB  - We operated on a 77-year-old woman with extensive thoracic aortic aneurysm by
      staged repair using the reversed elephant trunk technique. First, we performed
      descending aortic replacement with a 28-mm straight Dacron graft through a left
      lateral thoracotomy. Considering the high possibility of a proximal operation in
      the near future, the 10-cm invaginated proximal end of the graft was anastomosed
      to the aorta to facilitate subsequent operation on the upstream aorta. After a
      year of follow-up, a second-stage total arch replacement was performed because
      the aortic arch aneurysm had enlarged. The reversed elephant trunk was withdrawn
      under deep hypothermic circulatory arrest. Fibrin clots had formed within the
      folded graft, which could cause postoperative thromboembolism. After cleaning the
      inner surface of the withdrawn graft, the proximal branched conduit was
      anastomosed to it to complete the total arch replacement. We review this case and
      discuss possible mechanisms of and solutions for this condition.

PMID- 17444169
TI  - Thymolipoma associated with myasthenia gravis.
AB  - A 51-year-old woman with a 3-year history of diplopia was admitted to our
      hospital. Repetitive stimulation of the right median nerve revealed decreasing
      hand muscle responses. Edrophonium chloride administration alleviated the
      symptoms. The serum antiacetylcholine receptor antibody level was 3.3 nmol/l;
      thus, myasthenia gravis was diagnosed. A chest roentgenogram revealed a left
      inferior mediastinal mass, and a chest computed tomographic scan revealed a fat
      density mass partly containing soft tissue areas in the left side of the anterior
      mediastinum. Median sternotomy and extended thymectomy were performed. The
      pathology examination of the tumor revealed mature adipose tissue including
      islands of thymic tissue containing Hassall's corpuscles, without germinal
      centers. The tumor was a thymolipoma of the anterior mediastinum. Her
      postoperative course was good, and she is doing well at 1 year postoperatively.

PMID- 17444170
TI  - Primary malignant fibrous histiocytoma of the heart.
AB  - We describe a case of a primary cardiac malignant fibrous histiocytoma in the
      left atrium of a 72-year-old man. Local recurrences appeared twice, at 2 and 14
      months after initial tumor resection, and were managed surgically. The patient
      died of pancreatic metastasis 22 months after the initial diagnosis. The
      prognosis for MFH of the heart is poor despite aggressive surgical treatment.

PMID- 17444171
TI  - Traumatic aortic regurgitation caused by a detached commissure.
AB  - Case reports of traumatic aortic regurgitation caused by detached commissures are
      rare. We report a case of a 56-year-old man involved in a traffic accident.
      During his hospitalization for subdural hematoma and pulmonary contusion, he
      began to suffer from heart failure. He was operated on under diagnosis of severe
      aortic regurgitaion. The commissure between the left and the noncoronary cusps
      was largely detached from the aortic wall, which was easily estimated to be the
      cause of the prediagnosed left cusp prolapse. His aortic valve was replaced, and
      his postoperative course was uneventful.

PMID- 17444172
TI  - Truncus arteriosus repair after palliative bilateral pulmonary artery banding.
AB  - A 3.5-month-old girl was diagnosed with type I truncus arteriosus and severe
      pulmonary hypertension. We performed palliative bilateral pulmonary artery
      banding (right and left circumferences, 14 and 12 mm, respectively). Corrective
      repair for truncus arteriosus was then performed at 10 months of age. The good
      postoperative course in this patient demonstrates that palliative bilateral
      pulmonary artery banding is a useful surgical option for truncus arteriosus
      associated with pulmonary hypertension.

PMID- 17444173
TI  - Floating thrombus in the ascending aorta.
AB  - Floating thrombus in the ascending aorta is an uncommon source of embolism. We
      report a case of a 61-year-old man who was admitted to our hospital for transient
      brain ischemic attack. Transesophageal echocardiography showed a floating mass on
      the sinotubular junction. We started anticoagulation therapy immediately and
      performed surgical removal of the mass 5 days after the admission. Postoperative
      course was uneventful. He is now in good health and has no sign of recurrence.
      The etiology of this case is unclear, and the strategy is difficult to determine
      in terms of cerebral complications.

PMID- 17444174
TI  - Safety of perioperative hemodialysis and continuous hemodiafiltration for
      dialysis patients with cardiac surgery.
AB  - OBJECTIVE: We have routinely used postoperative continuous hemodiafiltration
      (CHDF) combined with intraoperative hemodialysis (IHD) for dialysis patients
      undergoing open-heart surgery. This perioperative management could avoid any
      limitation of potassium concentration in the cardioplegic solution, strict
      restriction of fluid administration, or blood transfusion. METHODS: To evaluate
      the safety of this strategy, 22 dialysis patients who underwent open-heart
      surgery (Dialysis Group) were retrospectively compared with 30 patients with
      normal renal function selected from the same time period with rigorously matched
      clinical characteristics such as age, gender, and operative procedures (Matched
      Group). RESULTS: No significant difference was found in the operative variables
      such as the operative procedures, cardiopulmonary bypass time, and aortic cross
      clamp time in both groups. There were two deaths (9.1%) in the Dialysis Group
      compared with Matched Group (0%). In the Dialysis Group, the levels of serum
      potassium and creatinine were well controlled in the perioperative period with a
      mean duration of IHD and CHDF of 243.7 +/- 60.6 min and 2.7 +/- 1.1 days,
      respectively. In particular, no significant difference between intraoperative and
      postoperative levels of serum potassium was observed in the Dialysis Group (P =
      0.09), whereas there was a significant increase in the Matched Group (P = 0.004).
      Mean volume administered for the first 24 h after surgery was not different from
      the Matched Group. There were no vascular access-related complications in the
      Dialysis Group. CONCLUSIONS: Postoperative CHDF combined with IHD can provide a
      similar management protocol for dialysis patients compared to patients with
      normal renal function.

PMID- 17444175
TI  - Late-onset chylothorax following extrapleural pneumonectomy for mesothelioma.
AB  - We report a 64-year-old woman treated with surgical intervention for late-onset
      chylothorax following a pleuropneumonectomy. The patient underwent an
      extrapleural pneumonectomy for diffuse malignant mesothelioma and was
      uneventfully discharged on postoperative day 29. Pleural effusion aspirated on
      postoperative day 9 was dark red. A chest roentgenogram taken at our outpatient
      clinic revealed a mediastinal shift on postoperative day 56. No bacterial
      infection was found in the milky effusion. We made a diagnosis of postoperative
      late-onset chylothorax based on the laboratory data obtained from tests of the
      pleural fluid. A repeat thoracotomy to ligate the lymphatic duct was performed
      because conservative management with chest tube drainage and no oral feeding was
      unsuccessful. The patient was discharged after the operation with a good clinical
      course.

PMID- 17444176
TI  - Radiation-induced valvular disease is the logical consequence of irradiation.
AB  - Mediastinal irradiation has been reported to induce cardiac diseases such as
      pericardial disease, accelerated arteriosclerosis of the coronary arteries,
      valvular disease, conduction abnormalities, and calcification of the aorta. We
      experienced four cases of radiation-induced valvular disease. All patients had
      histories of radiation therapy and had aortic valve disease. All patients had
      marked fibrosis of the mediastinum and hypertrophy of pericardium. The aortic
      valve leaflets were tricuspid and fibrotic with focal dystrophic calcification
      and markedly thickened. In the pathological findings, certain rheumatic
      endocarditis changes such as endocardial reduplication and vascularization were
      not found in all aortic valves. The mechanism of radiation-induced cardiac
      disease is not clear. However, those changes seem to progress very slowly. Thus,
      long-term follow-up care is particularly important for patients undergoing
      radiation therapy. Fortunately, today's irradiation techniques are much less
      harmful; therefore, radiation-induced cardiac disease will likely become more
      rare in the future.

PMID- 17444177
TI  - Double-outlet right ventricle with left malposition of the great arteries and
      total anomalous pulmonary venous connection.
AB  - The patient was diagnosed with double-outlet right ventricle with left
      malposition of the great arteries, total anomalous pulmonary venous connection,
      and pulmonary stenosis at 2 months of age. Because the progression of pulmonary
      venous obstruction was suspected at 2 years of age, the patient was catheterized
      and underwent a definitive repair. The patient had a right aortic arch and left
      juxtaposition of the atrial appendages; the intraventricular anatomy exhibits
      malalignment between the conal septum and the muscular intraventricular septum,
      and the conal septum is well developed and dextroposed, resulting in pulmonary
      obstruction and multiple ventricular septal defects (VSDs). Because a
      supracardiac type (Darling's type Ib) of total anomalous pulmonary venous
      connection was also combined with such an anomaly, total correction consisted of
      an anastomosis of the left atrium and the common pulmonary vein, creation of an
      intraventricular tunnel, direct closures of muscular VSDs, pulmonary valvotomy,
      and infundibular resection. To our knowledge, this is the first description of
      the successful surgical correction of this type of anomaly in one stage.

PMID- 17444178
TI  - A case of tuberculous endocarditis with acute aortic valve insufficiency and
      annular subvalvular left ventricular aneurysm.
AB  - Tuberculous endocarditis is an exceptionally rare disease, and its surgical
      operation has been reported in only one case. This is a successful surgical
      report of acute aortic insufficiency caused by tuberculous endocarditis
      associated with annular subvalvular left ventricular aneurysm (ASLVA) beneath the
      aortic valve. This patient had acute left ventricular failure and
      cardiorespiratory arrest and suffered from multiple organ dysfunction and
      coagulopathy disorder. Urgent surgery was performed to replace the aortic valve
      with the approximation of ASLVA. Histopathological findings of the excised aortic
      cusps gave the diagnosis of tuberculous endocarditis, and antituberculous drug
      administration started on the first postoperative day. Postoperative recovery has
      been uneventful without relapse of tuberculosis for 7 postoperative years.

PMID- 17444179
TI  - Giant pulmonary cyst associated with congenital pericardial defect.
AB  - Congenital defects of the pericardium are rare. This report describes a young
      woman with a congenital complete pericardial defect who developed a giant
      pulmonary cyst. After operation the patient experienced chest pain caused by
      myocardial ischemia due to cardiac displacement. It is important to note that
      heart lability in patients with congenital pericardial defects may cause grave
      complications after thoracotomy associated with volume loss of the residual lung.

PMID- 17444180
TI  - Reconstruction of a friable posterior mitral annulus after removing a calcified
      artificial ring using flipover technique of the anterior mitral leaflet.
AB  - We report a new technique for reinforcement of a friable posterior mitral annulus
      using the anterior leaflet after removing a calcified artificial ring. A 72-year
      old woman underwent mitral valve replacement for mitral stenosis and recurrence
      of regurgitation after mitral valve repair at 53 years of age. She had been on
      chronic hemodialysis for 20 years. The posterior mitral annulus became highly
      friable after debridement of the calcified artificial ring. The anterior mitral
      leaflet was detached from its annulus and transferred to the posterior annulus to
      cover the defect. The anterior leaflet was anchored to the posterior annulus by
      valve sutures, and mitral valve replacement was performed successfully.
      Postoperative ultrasonic cardiography revealed preservation of left ventricular
      function with no perivalvular leakage.

PMID- 17444181
TI  - Spontaneous innominate artery perforation presenting as hemoptysis.
AB  - An 86-year-old man with a history of asthma and hypertension suddenly developed
      hemoptysis. A computed tomographic (CT) scan demonstrated a right-sided
      paratracheal mass adjacent to the aortic arch that had not been recognized on a
      CT scan 5 months before. Angiography revealed extravasation of the contrast agent
      from the innominate artery. These findings suggested innominate artery
      perforation resulting in a pseudoaneurysm. At the time of operation, an
      approximately 3-cm defect was noted at the right side of the innominate artery.
      The aneurysmal cavity was inspected through the tear of the innominate artery,
      and there was no purulent fluid or thrombus. A prosthetic graft interposition
      between the origin of the innominate artery and the bifurcation of the common
      carotid artery and subclavian artery was performed under cardiopulmonary bypass.
      Histologic study of the innominate artery revealed only atherosclerotic changes.
      There was no evidence of infection or malignancy. The hemoptysis disappeared
      postoperatively.

PMID- 17444182
TI  - Repeated transluminal endovascular Inoue stent graft placement for progressive
      dilatation of prosthetic graft that had been repaired with Inoue stent graft
      placement for dilatation 23 years after extraanatomical bypass.
AB  - A 76-year-old man had undergone aneurysm exclusion and ascending abdominal aortic
      extraanatomical bypass for a thoracoabdominal aortic aneurysm in 1978. In 1983
      hemoptysis occurred, and resection and closure of the central stump of the aorta
      and a left lower lobectomy were performed. Dilatation (phi50 mm) of a prosthetic
      graft (Cooley Graft phi18 mm) used for extraanatomical bypass was noted in 2001
      and was repaired by placement of an Inoue stent graft. However, the aneurysm
      diameter increased further (phi70 mm), although no endoleak was noted: Placement
      of an Inoue stent graft covering the whole length of the prosthetic graft was
      repeated in 2006. The postoperative course was smooth, no endoleak occurred, and
      the patient was discharged 2 weeks after surgery.

PMID- 17444183
TI  - For more safety: no-knife stapling for vascular division during video-assisted
      thoracoscopic surgery.
AB  - Staple cutters facilitate video-assisted thoracoscopic surgery, but their
      potential malfunction at vascular division can threaten the patient's life. We
      have used no-knife staplers and have divided between the staple lines without
      event. We show this technique to be a risk management alternative.

PMID- 17444185
TI  - Deciphering daddy's DNA.

PMID- 17444184
TI  - 'It's all about me'.

PMID- 17444186
TI  - Vitamins and good sense.

PMID- 17444187
TI  - Genetic diversity of Y-chromosome microsatellites in the Fujian Han and the
      Sichuan Han populations of China.
AB  - Y-chromosome short tandem repeats (STRs) are potentially useful for forensic,
      anthropological and evolutionary studies. In this study we chose the loci DYS 19,
      DYS 388, DYS 389 I, DYS 389 II, DYS 390, DYS 391, DYS 392, DYS 393, DYS 425 and
      DYS 426. Blood samples were taken from 46 unrelated male individuals from Fujian
      Han and 43 unrelated males from Sichuan Han in China. DNA was extracted by
      conventional chelex extraction procedure. PCR was carried out in two multiplex
      reactions. Fragment analysis was conducted on an ABI PRISM 310 Genetic Analyzer.
      Allele frequency distributions and discrimination indices were calculated, and
      the two populations were tested for genetic differences by means of analysis of
      molecular variance (AMOVA). Here we obtained 75 Y-STR haplotypes and the
      haplotype diversity for the complete haplotype was 0.9884 in Fujian Han and
      0.9967 in Sichuan Han. A larger genetic difference became apparent between the
      two populations that belong to the Sino-Tibetan speaking populations.

PMID- 17444188
TI  - Regional, age and sexual differences of BMI of the Czech and Slovak adult
      populations at the end of the 20th century.
AB  - Nowadays the Body Mass Index (BMI) is used everywhere as the coefficient of
      normal weight, overweight and obesity. In the years 1987-1988 an anthropometrical
      survey was carried out in the whole region of the former Czechoslovakia, which
      was done on 20,232 adult males and females, aged from 18 to more than 70 years.
      The research was made on the basis of three grade statistical choice and is
      representative for the entire territory of the Czech and Slovak Republics. Body
      height and body weight were determined according to Martin & Saller (1957; M 1, M
      71). For the assessment of regional differences the whole set of data was divided
      into 12 separate groups in accordance to the administrative regions existing at
      that time. Each group was then analyzed considering eleven age classes.

PMID- 17444189
TI  - Dietary patterns and lifestyle in a sample of a Slovak Romany community.
AB  - The aim of this paper is to evaluate dietary habits and behavioural factors
      related to atherosclerosis in Slovak Romany, the large minority, characterized by
      high cardiovascular morbidity. The study involved 150 Romany volunteers (68
      males, mean age 42.1 +/- 13.9 y and 82 females, mean age 40.9 +/- 13.7 y).
      Dietary data were obtained by a validated food-requency questionnaire and a
      single 24-hour dietary recall. The nutrient intake and health behaviour of the
      Romany population is not consistent with current guidelines for atherosclerosis
      prevention. The mean intake of fat is higher than the recommended dietary
      allowance (RDA), especially in males (155.3 % of RDA). In females the intake of
      alpha-linolenic acid is low, in males the cholesterol content of the food exceeds
      the acceptable value. The mean intake of protein is higher than the
      recommendation (males 153% of RDA, females 122.2%), with a high proportion of
      animal protein. In both sexes the mean intake of vitamins is below the RDA. In
      comparison to the general population the diet of the Romany males contains
      significantly more animal protein (p < 0.05), less plant protein (p < 0.05) and
      folate (p < 0.01). In the diet of the Romany females a significantly lower intake
      of plant protein (p < 0.05) and vitamin E (p < 0.05) was observed, as well as a
      lower intake of linoleic acid and iron in both sexes. The cumulation of ten
      selected cardiovascular risk factors showed that particularly the Romany males
      could be considered as having more atherogenic profile.

PMID- 17444190
TI  - Five-class height-weight mean and SD system applying Estonian reference values of
      height-weight mean and SD for systematization of seventeen-year-old conscripts'
      anthropometric data.
AB  - A study of 739 conscripts aged 17 years from the town of Tartu and from the Tartu
      county was performed. Height, weight, 33 anthropometric measurements and 12
      skinfolds were measured. The data were classified into five height-weight mean
      and SD-classes applying the Estonian reference values for this age and sex
      (Grunberg et al. 1998). There were 3 classes with conformity between height and
      weight class: 1--small (small height and small weight), 2--medium (medium height
      and medium weight), 3--large (large height and large weight), 4--weight class
      dominating (pyknomorphic) and 5--height class dominating (leptomorphic). It was
      found, that in classes 1, 2 and 3 the height and weight increase was in
      accordance with the increase in all heights, breadths and depths, circumferences,
      skinfolds, body fat, muscle and bone mass. In class 4 circumferences, skinfolds,
      body fat and muscle mass were bigger. In class 5 all heights and the relative
      bone mass were bigger. The present investigation confirms the assumption that the
      five height-weight mean and SD five-class system applying the Estonian reference
      values for classifying the anthropometric variables is suitable for seventeen
      year-old conscripts. As well the border values of 5%, 50% and 95% for every
      anthropometrical variable in the five-classes were calculated, which may be
      helpful for practical classifying.

PMID- 17444191
TI  - Using a height-weight classification for analysis of food energy and main
      nutrient contents in 24-hours menus of 17-23-year-old Estonian female students.
AB  - The study is focused on creating an anthropometric model that would enable to
      associate the body build peculiarities with nutritional variables. Thirty-six
      body measurements and 12 skinfolds were measured on 131 17-23-year-old female
      students of the University of Tartu, and 12 body composition characteristics were
      calculated. The subjects had to submit descriptions of their 24-hour menus.
      Nutrient intake was determined using the Micro-Nutrica software and the food
      composition database; the energy (in kcal) and main nutrients (proteins, fats and
      carbohydrates) content in the subjects' 24-hour menus were calculated. All body
      measurements were compared with nutritional variables, and 29 anthropometric
      variables were found that showed statistically significant correlations with at
      least one nutrient characteristic. The amount of food consumed correlated
      positively with body density and negatively with weight, circumferences,
      skinfolds and all indicators of body fat content (r reached 0.32). To associate
      body size, shape and composition with the amount of food consumed, a 5 SD height
      and weight classification was used, which consisted of three classes of
      concordance between height and weight (small, medium, large) and two classes of
      disconcordance - pyknomorphs and leptomorphs. All the 29 body measurements and
      nutrient variables were distributed systematically between the different classes.
      The pyknomorphous class with its greater body fat content and smaller density
      contrasted clearly with the class of leptomorphs. Food consumption in total as
      well as per 1 kg of body weight was smaller in pykniks than in leptosomes.
      Protein consumption did not reveal statistically significant differences. In
      small, medium and large classes, consumption of energy, fats and carbohydrates
      could not be proved about protein consumption. One should not overestimate the
      significance of BMI in nutritional studies. BMI characterises only obesity and
      cannot replace the characterisation of different body types. In our study, BMI of
      the small and the leptosomic class was almost equal, although these body types
      differ greatly from each other.

PMID- 17444192
TI  - Sexual dimorphism from birth to age 60 in relation to the type of body shape.
AB  - Sexual dimorphism depends on age. It can be analysed within a population by a
      comparison of sex-specific body measurements based on cross-sectional samples. We
      analysed four length measurements, three circumferences, and one skinfold
      diameter of a representative cross-sectional sample of healthy German subjects
      aged 0 to 65 years. We here report that sexual dimorphism of these body
      measurements already is present in newborns. The percentages of anthropometric
      differences between female and male subjects behave in a specific pattern during
      growth age from birth up to adolescence. Girls are born smaller on an average,
      but they have a more accelerated growth than boys. Girls reach the peak of their
      adolescent growth spurt earlier in their chronological age. This means that their
      biological age at this time is at least 2 years older than that of boys of the
      same chronological age. This sex-specifically differential onset of the
      adolescent growth spurt, and its peak, as well as the differential decrease of
      growth velocity cause a dramatic change in sexual dimorphism. This change is
      clearly shown in this cross-sectional study. Except for the subcutaneous fat
      layer, there is a clear male growth advantage in all of the measurements
      investigated after the peak of the adolescent growth spurt. The largest
      differences between the measurements of both sexes in favour of the male sex are
      reached at young adult age. In the further course of life, the anthropometrical
      differences between the sexes decrease again. Sexual dimorphism within a
      population at a defined chronological age is therefore not only the result of a
      developing sex-specific physique, but also the result of a sex-specific growth
      velocity during the successive stages of biological development. Interestingly,
      we found that the sex-specific velocity of physical development, and by this the
      development of sexual dimorphism, proceeds differently in the tall and slim
      leptomorphic individuals in comparison to the smaller and more corpulent
      pyknomorphic individuals.

PMID- 17444193
TI  - Interrelationship of waist circumference and subcutaneous fat with metabolic and
      blood pressure measures among Asian Indian men.
AB  - People of South Asian origin (e.g. Indians) usually have a more centralized
      distribution of body fat with thick trunk skinfolds and markedly higher mean
      waist circumference (WC) for a given level of body fat percentage compared to
      Europeans and are exceedingly susceptible to coronary heart disease (CHD)
      worldwide. Owing to ethnic heterogeneity, population specific information on the
      interrelationship of fat topography with metabolic and blood pressure measures in
      different Indian populations is immediately required. In view of the above
      consideration the present work was undertaken to study the interrelationship of
      the WC and the sum of four (biceps, triceps, subscapular, suprailiac) skinfolds
      (SF4) with metabolic and blood pressure variables among the well-off Bengalee men
      aged 30 years and above from Calcutta and suburbs. The sample of the present
      study comprises 212 male railway employees of the Eastern Railway, Government of
      India. All 212 subjects were residents of Calcutta and its suburbs.
      Anthropometrics, lipids (total cholesterol, fasting triglyceride, high, low and
      very low density lipoprotein cholesterol), fasting plasma glucose and blood
      pressure measures were taken from each participant. Two-sample (unpaired) t-test
      revealed that centrally obese men (waist circumference=90 cm) had significantly
      greater means compared to centrally non-obese subjects for metabolic risk factors
      and blood pressure. Inter-tertile comparison of lipids, lipoproteins and glucose
      revealed that there existed no significant differences in their distribution
      according to SF4 tertiles. The results of multiple regression analyses (after
      controlling for the linear, cubic and quadratic effect of age) using waist
      circumferences and SF4 as independent variables demonstrated the significant
      effect of central obesity on metabolic and blood pressure variables in the study
      population. This finding indicated the clinical and physiological importance of
      central body fat accumulation particularly in and around the waist line in
      explaining risk factors for chronic diseases, e.g. CHD.

PMID- 17444194
TI  - Inbreeding effects on the growth in stature among Telaga boys and girls of
      Kharagpur, West Bengal, India.
AB  - The present study is an attempt to understand the genetical effects of inbreeding
      on the process of growth. The inbred and non-inbred subjects were selected on the
      basis of extensive pedigrees of five generations in the Telaga, an endogamous
      population of Kharagpur, India. Preference was given to cousins belonging to the
      same kindreds while selecting control sample so that environmental variation was
      minimized. Altogether 633 boys and 614 girls of different inbreeding levels aged
      five to twenty years were measured for stature. Analysis has been done in
      different levels of inbreeding in each age and sex on mean annual increments and
      variances of increments. The results revealed that comparison of annual increment
      for each age between boys and girls with different degrees of inbreeding and
      application of the one-tailed t-test of significance does not provide any
      evidence of inbreeding effect on mean increment for stature studied in either
      sex. This might indicate the absence of marked dominant/recessive effects of
      genes determining annual increments in body size rather than the absence of
      genetical control of increments due to growth. Moreover, it is noteworthy that
      the variance of annual increment due to growth (which is estimated indirectly)
      consistently increases with increase of inbreeding level with only a few
      exceptions. The exceptions occur more often in girls than in boys, which can be
      explained by greater environmental stress and selection pressure and variation in
      X-linked inbreeding among girls. This would be worthwhile to verify in
      longitudinal growth data in future. Increased variances of annual increment with
      inbreeding, in the absence of change of mean increment on inbreeding, would
      indicate the influence of additive autosomal genes for the process of physical
      growth in children in either sex. A close scrutiny of the annual increments for
      the measurements in all the four levels of inbreeding in either sex fails to
      bring out any consistent trend of change in the age of adolescent spurt with
      inbreeding. This might suggest an underlying homozygosity of several genes with
      inbreeding in the population.

PMID- 17444196
TI  - [Diagnostic and therapeutic progress in cardiology].

PMID- 17444195
TI  - [Evolutional and biological aspects of placentophagia].
AB  - Over the last 30 years it could be observed that a very small minority of modern
      humans consumes the human placenta that belongs to the afterbirth. This behavior,
      which is known by the technical term of placentophagia, is the focal point of the
      present essay. Placentophagia is a behavior common among almost all kinds of
      mammals, even primates can be observed ingesting at least amniotic fluid during
      the birth. However, humans of traditional human cultures consume the afterbirth
      only in rare cases. In detail, the present essay discusses the hypothesis that
      human placentophagia has a phylogenetic basis and the hypothesis that human
      placentophagia is physiologically reasonable. It is concluded that the behavior
      of the human placentophagia neither possesses a phylogenetic basis nor can be
      regarded as physiologically reasonable.

PMID- 17444197
TI  - [Treatment of acute myocardial infarction in 2007].
AB  - The two immediate priorities when faced with acute myocardial infarction are 1)
      to be able to deliver electric cardioversion in case of need and 2) to rapidly
      start reperfusion therapy (angioplasty or thrombolysis). During the hospital
      phase, antiplatelet agents are given to all, betablockers should be used if there
      is no heart failure, and ACE-inhibitors are mostly indicated for patients with
      poor hemodynamics. At discharge, in addition to instructions regarding not
      smoking, a balanced diet, and regular physical exercise, a statin and
      antiplatelet therapy remain a long-term indication for all. ACE inhibitors should
      be continued in case of high blood pressure, heart failure or a left ventricular
      ejection fraction < 40%. The main benefit of betablockers is for patients with
      residual angina and/or chronic heart failure.

PMID- 17444198
TI  - [Are drug-eluting stents dangerous?].
AB  - The use of drug-eluting stents has brought considerable change to the treatment
      of coronary artery disease. However, recent reports have suggested that they may
      be associated with an increase risk of late thrombosis. A current analysis of the
      available data suggests that the risk of late thrombosis is indeed probably
      higher with drug-eluting stents than with bare metal stents. However, this risk
      appears low, and does not justify withholding the device from the patients who
      would benefit from their use, especially when they suffer from complex disease
      (long lesions, small vessels, diabetes, etc) with a known higher risk of
      recurrent stenosis. Based on the information available to us today, appropriate
      patient selection, meticulous implantation technique and uninterrupted dual
      antiplatelet therapy (aspirin and clopidogrel) for six to twelve months after
      angioplasty appear to be the main ingredients for a successful and uncomplicated
      procedure.

PMID- 17444199
TI  - [Exercice echocardiography in 2007].
AB  - Exercise echocardiography is performed with transthoracic echocardiography
      recorded during ergometry in order to detect and evaluate coronary heart disease.
      In experienced hands this technique is safe, comfortable and easy to perform. It
      is mainly indicated for patients with intermediate probability of coronary
      disease. Performances are identical to myocardial scintigraphy or cardiac MRI
      with significant less costs.

PMID- 17444200
TI  - [Blood pressure variability: clinical interest or simple curiosity?].
AB  - Blood pressure variability is a physiological phenomenon influenced by many
      internal and external factors. This variability could be also influenced by
      pathological conditions such as arterial hypertension. Two forms must be mainly
      distinguished: the blood pressure variability at long and short-term. The latter
      could only be studied by continuous recordings. In this article will be analysed
      the interest of measuring blood pressure variability, its cardiovascular
      prognosis and the therapeutic tools when it is increased.

PMID- 17444201
TI  - [Sleep apneas and cardiac arrhythmias: is there a role for cardiac pacing?].
AB  - Sleep apneas are very common in general practice; they affect quality of life and
      cause significant morbidity and mortality with cardiovascular complications. We
      resume the principal consequences of sleep apneas and point out the place of
      cardiac pacing in this syndrome.

PMID- 17444202
TI  - [Aid to development of cardiac surgery in the emerging world: mutual benefits?].
AB  - Aid to the development of cardiac surgery in the emerging world is mandatory to
      help these countries develop their own capacities of treatment for their
      patients. A personal experience of ten years involvement with such projects is
      described, as well as the means and difficulties to achieve tangible results in
      this field.

PMID- 17444203
TI  - [Metabolic and endocrine effects of antihypertensive drugs].
AB  - Antihypertensive therapy has been associated with 35 to 40% reduction in stroke
      incidence and 20 to 25% reduction in myocardial infarction. Antihypertensive
      drugs have various metabolic and endocrine activities. Their effect on
      electrolytes and hormones which modify the serum levels of electrolytes (such as
      aldosterone, angiotensine II and brain natriuretic peptide) is reviewed.
      Antihypertensive drugs may also modify risk factors for cardiovascular disease
      such as cholesterol, CRP hs, as well as urate acid and insulin resistance.
      Diuretics and betablockers increase this resistance whereas, it is decreased by
      certain enzyme conversion inhibitors and certain angiotensine II receptor
      blockers, partially through adiponectin release. Endocrine side effects of
      antihypertensive drugs such as weight gain, diabetes, gout, osteoporosis,
      impotence are discussed. They may decrease adherence to medication. Therefore we
      recommend if possible a low dose combination of antihypertensive drugs.

PMID- 17444204
TI  - [Patients: could you wait patiently a little longer? (2). Access of American
      patients to experimental drugs].

PMID- 17444205
TI  - [Multiple myeloma].

PMID- 17444206
TI  - [Assisted suicide: clear individual problem, complex community dimension].

PMID- 17444207
TI  - [Medical communication and relational recommendations: countercurrent].

PMID- 17444208
TI  - [Several ethical precautions before entering the nanoworld (I)].

PMID- 17444209
TI  - [On France and on neo-eugenics (5)].

PMID- 17444210
TI  - [Against malaria: ASAQ, one dollar per box].

PMID- 17444211
TI  - [70% said "no" and open wounds].

PMID- 17444212
TI  - Food analysis is an invaluable tool for the comprehension of the factors that
      determine food quality.

PMID- 17444213
TI  - High performance liquid chromatography and capillary electrophoresis in the
      analysis of soybean proteins and peptides in foodstuffs.
AB  - The increasing interest in functional and healthy food products has promoted the
      use of soybean in the manufacture of foods for human consumption. Soybean basic
      products (soybeans, textured soybean, soybean flour, soybean protein concentrate
      and soybean protein isolate) as well as soybean derivatives (soybean dairy-like
      products, soybean drinks with fruits, meat analogues, etc.) are commercially
      available. In addition, due to the interesting nutritional and functional
      properties of soybean proteins, they are usually employed as ingredient in the
      elaboration of a large number of food products such as bakery or meat products
      among others. In spite of the good characteristics of soybean proteins, their
      addition to some products is forbidden or allowed up to a certain limit.
      Therefore, analytical methodologies to achieve the determination of soybean
      proteins in foods are necessary in order to make possible adequate quality
      control and to prove that legal regulations controlling their addition are
      accomplished. However, this is not an easy task due to the diversity and
      complexity of the food matrices and the technological treatments to which some of
      these foods are submitted during their elaboration. This article presents for the
      first time a comprehensive review on the analytical methodologies developed using
      HPLC and CE to characterize soybeans and to analyse soybean proteins in meals.
      Moreover, the use of HPLC and CE in the characterization of soybean protein
      fractions and their hydrolyzates, and a study of their relationships to
      nutritional, functional and biomedical properties are included. Finally, the
      application of proteomic methodologies in soybean food technology is also
      reviewed.

PMID- 17444214
TI  - Analytical determination of antioxidants in tomato: typical components of the
      Mediterranean diet.
AB  - Diets in the countries of the Mediterranean basin are characterised by abundant
      plant foods (fruits, vegetables, breads, nuts, seeds, wine, and olive oil) and
      include fish and low-fat dairy products. Among the vegetables, tomatoes are a
      main component of the traditional Mediterranean diet, which has been associated
      with health protection and longevity. Eating tomatoes has been associated with
      reduced risks of some types of cancer and other diseases. These beneficial
      properties appear to be related to the antioxidant content of the fruit,
      particularly carotenoids (lycopene and beta-carotene), ascorbic acid, and
      phenols, which may play a role in inhibiting reactions mediated by reactive
      oxygen species. Due to the importance of antioxidant compounds in tomatoes and
      tomato products, we present here an overview of current analytical methods (from
      2000 until the present date) for determining the different antioxidants. The
      analytical procedures used to determine individual compounds involve extraction
      from the sample, analytical separation, and quantification. The choice of
      analytical method depends on the particular focus of the analysis and the kind of
      product analysed. High-performance liquid chromatography is the technique of
      choice for the analysis of tomato antioxidants.

PMID- 17444215
TI  - Temperature effects on separation on zirconia columns: applications to one- and
      two-dimensional LC separations of phenolic antioxidants.
AB  - The effects of temperature and mobile phase on LC chromatographic separation of
      phenolic antioxidants on zirconia-based columns were investigated. Unlike silica
      based materials, zirconia columns show excellent thermal stability over a wide
      range of temperatures and enable high-temperature separations. Enthalpic and
      entropic contributions to the retention of phenolic compounds on ZR-Carbon and ZR
      Carbon C18 columns were determined from retention versus temperature plots in
      order to elucidate the retention mechanism of sample compounds over the
      temperature range up to 14 degrees C. High-temperature liquid chromatography on
      ZR-Carbon columns was used for comprehensive LC x LC two-dimensional separation
      systems based on the different selectivity of a Zorbax SB micro-column used in
      the first dimension and a ZR-Carbon column used in the second dimension. Two
      dimensional LC x LC systems employing a setup with two alternately operated
      parallel ZR-Carbon columns in the second dimension were used for the analysis of
      phenolic antioxidants in beer and wine samples.

PMID- 17444216
TI  - Simple and rapid characterization of soybean cultivars by perfusion reversed
      phase HPLC: application to the estimation of the 11S and 7S globulin contents.
AB  - A perfusion RP HPLC method enabling the separation of soybean proteins in an
      analysis time lower than 3 min has been used to obtain the chromatographic
      profiles of different soybean cultivars. The chromatograms obtained for each
      soybean variety presented clear differences that justified the potential use of
      this method for cultivar characterization. The area percentages obtained were
      employed as variables for cluster and principal components analysis of these
      soybeans. The application of these multivariate methods enabled the grouping of
      the soybeans in different categories. The protein fractions obtained from these
      soybeans by the application of a fractionation method were also analyzed. The
      chromatographic profiles obtained enabled the assignment of peaks to the main
      soybean proteins (7S and 11S globulins). These data were used for the estimation,
      for the first time, of the 7S and 11S globulin contents in soybean cultivars.

PMID- 17444217
TI  - Determination of polyacetylenes in carrot roots (Daucus carota L.) by high
      performance liquid chromatography coupled with diode array detection.
AB  - A new high-performance liquid chromatographic method with diode array detection
      was developed for the separation and simultaneous determination of the carrot
      polyacetylenes falcarindiol (FaDOH), falcarindiol 3-acetate (FaDOAc) and
      falcarinol (FaOH) in carrot root extracts. The optimal chromatographic conditions
      were achieved on a C18 column with a linear gradient elution of water and
      acetonitrile as mobile phases, at the flow rate of 1.0 mL/min. All calibration
      curves of the three carrot polyacetylenes showed good linear regression (R2 >
      0.998) within the test ranges. The developed method showed good precision for
      quantification of all polyacetylenes with overall intraday and interday variation
      of less than 3.3% and with average recovery rates of 99.2, 96.8 and 99.7% for
      FaDOH, FaDOAc and FaOH, respectively. The LOD (S/N = 3) and LOQ (S/N = 10) were
      less than 0.19 and 0.42 microg/mL, respectively, for all analytes. The
      established method was successfully used to determine the spatial distribution of
      FaDOH, FaDOAc and FaOH in six carrot genotypes (Bolero, Independent, Line 1,
      Mello Yello, Purple Haze and Tornado) by analysing peeled carrots and the
      corresponding peels for these polyacetylenes.

PMID- 17444218
TI  - Composition and content of seed flavonoids in forage and grain legume crops.
AB  - Flavonoid content and composition in 124 accessions of forage and grain legumes
      was assessed by means of HPLC-DAD and HPLC-ESI-MS analyses of seed extracts.
      Excluding soybean, only 7 out of 77 grain legume accessions exhibited a total
      flavonoid content higher than 0.1 mg/g fresh seed weight (mean content 0.33 +/-
      0.31 mg/ g fresh seed weight); while in 38 out of 47 forage legume, the mean
      flavonoid content was 1.49 +/- 0.89 mg/g fresh seed weight. On the basis of their
      higher seed flavonoid content and agronomic relevance, two grain and five forage
      legume accessions were selected for further HPLC-ESI-MS analyses aimed to
      identify bioactive compounds. Chemical analysis of the selected accessions
      permitted the identification of several flavonoids with pharmaceutical properties
      such as vitexin in Vigna angularis and Trigonella foenum-graecum, quercetin in
      all Trifolium spp and Medicago sativa, taxifolin in Trifolium pratense and
      Trifolium alexandrinum, myricetin in Trifolium repens, kaempferol in Phaseolus
      vulgaris and T. repens and luteolin in M. sativa and T. alexandrinum. Since much
      of literature information is regarding flavonoid content and composition of the
      green part of legume species, the obtained results contributed to fill the gap in
      knowledge about flavonoid content at the seed level.

PMID- 17444219
TI  - Chromatographic and electrophoretic approaches for the analysis of protein
      quality of soy beverages.
AB  - Furosine, generated by acid hydrolysis of fructosyllysine, an early Maillard
      reaction product, is a highly valuable indicator of food quality and, more
      specifically, of food protein quality. Ion pair RP-HPLC and CZE techniques were
      employed to determine furosine content in beverages based on soymilk (n = 15) and
      cow's milk supplemented with soy isoflavones (n = 1). The levels of furosine
      found in the samples ranged from 25.55 +/- 0.18 to 170.72 +/- 10.4 mg/100 g of
      protein by HPLC and from 28.67 +/- 1.84 to 161.25 +/- 5.78 mg/100 g of protein by
      CZE. Results obtained by both analytical techniques do not differ significantly
      (p > 0.05), confirming their feasibility for furosine analysis in soy-based
      products.

PMID- 17444220
TI  - Rapid analysis of food products by means of high speed gas chromatography.
AB  - Since the invention of GC, there has been an ever increasing interest within the
      chromatographic community for faster GC methods. This is obviously related to the
      fact that the number of samples subjected to GC analysis has risen greatly.
      Nowadays, in routine analytical applications, sample throughput is often the most
      important aspect considered when choosing an analytical method. Gas
      chromatographic instrumentation, especially in the last decade, has been
      subjected to continuous and considerable improvement. High-speed injection
      systems, electronic gas pressure control, rapid oven heating/cooling and fast
      detection are currently available in a variety of commercial gas chromatographs.
      The main consequence of this favourable aspect is that high-speed GC is being
      increasingly employed for routine analysis in different fields. Furthermore, the
      employment of dedicated software makes the passage from a conventional to a fast
      GC method a rather simple step. The present review provides an overview of the
      employment of fast GC techniques for the analysis of food constituents and
      contaminants. A brief historical and theoretical background is also provided for
      the approaches described.

PMID- 17444221
TI  - Comparison of comprehensive two-dimensional gas chromatography-time-of-flight
      mass spectrometry and gas chromatography-mass spectrometry for the qualitative
      characterisation of roasted barley by solid-phase microextraction.
AB  - Volatile compounds of roasted barley used in the production of barley coffee, the
      most common coffee substitute, were analysed by using solid-phase microextraction
      (SPME) followed by GC-MS and comprehensive GC x GC-TOF-MS, respectively. The
      optimised SPME extraction conditions in terms of selection of the fibre coating,
      extraction time and extraction temperature allowed to obtain the highest GC
      response, thus enhancing the identification capabilities of the developed method.
      As for the SPME-GC x GC-TOF-MS analysis, 64 compounds with similarity, reverse
      and probability values above 800, 900 and 6000, respectively, were identified, by
      using a polar x apolar column set combination; in contrast, GC-MS was able to
      identify a lower number of compounds, i.e. 40 volatiles.

PMID- 17444222
TI  - Solid phase microextraction-comprehensive two-dimensional gas chromatography-time
      of-flight mass spectrometry for the analysis of honey volatiles.
AB  - Head-space solid phase microextration (SPME), followed by comprehensive two
      dimensional gas chromatography-time-of-flight mass spectrometry (GCxGC-TOFMS),
      has been implemented for the analysis of honey volatiles, with emphasis on the
      optimal selection of SPME fibre and the first- and second-dimension GC
      capillaries. From seven SPME fibres investigated, a
      divinylbenzene/Carboxen/polydimethylsiloxane (DVB/CAR/PDMS) 50/30 microm fibre
      provided the best sorption capacity and the broadest range of volatiles extracted
      from the headspace of a mixed honey sample. A combination of DB-5ms x SUPELCOWAX
      10 columns enabled the best resolution of sample components compared to the other
      two tested column configurations. Employing this powerful analytical strategy led
      to the identification of 164 volatile compounds present in a honey mixture during
      a 19-min GC run. Combination of this simple and inexpensive SPME-based
      sampling/concentration technique with the advanced separation/identification
      approach represented by GCxGC-TOFMS allows a rapid and comprehensive examination
      of the honey volatiles profile. In this way, the laboratory sample throughput can
      be increased significantly and, at the same time, the risk of erroneous
      identification, which cannot be avoided in one-dimensional GC separation, is
      minimised.

PMID- 17444223
TI  - Use of SPE-GC/EIMS for residue analysis in wine elaborated from musts spiked with
      formulations of chlorpyriphos-methyl, methiocarb, dicofol, and cyproconazol.
AB  - The likely presence in wine of residues of the active ingredient and its
      degradation products, besides the byproducts and excipients of the commercial
      formulation, has been investigated for four pesticides. Formulations containing
      chlorpyriphos-methyl, methiocarb, dicofol, and cyproconazol were added to must,
      which was subjected to a usual vinification. The wines elaborated from must
      spiked with the formulation of chlorpyriphos-methyl contained two pyridinol
      compounds in addition to excipients such as alkylbenzenes, naphthalene, and
      methylnaphthalenes. Methiocarb was hydrolyzed to yield the corresponding phenol,
      and various unidentified compounds related to cyproconazol were observed in wine.
      The residues of the dicofol-containing formulation resulted to be dechlorination
      products; impurities from its commercial formulation were also detected in must
      and wine extracts. White wines contained higher amounts of residues than red
      wines. The residues were detected after an SPE followed by GC/EIMS in the scan
      mode. The concentrations of the active ingredients were determined by a matrix
      matched calibration to avoid quantitative errors arising from the matrix.

PMID- 17444224
TI  - A GC method for simultaneous analysis of bornesitol, other polyalcohols and
      sugars in coffee and its substitutes.
AB  - A GC method has been developed for the determination of polyalcohols and sugars
      in aqueous extracts from green coffee beans, ground roasted coffee beans
      submitted to either conventional or torrefacto processes, coffee blends and
      soluble instant coffees. Bornesitol was detected in aqueous coffee extracts for
      the first time. Mannitol, myo-inositol, mannose, fructose, galactose, glucose and
      sucrose have also been determined. Results seem to indicate that coffee
      manufacturing processes, such as roasting or decaffeination, do not affect the
      polyalcohol content. Coffee substitutes based on cereals, carob or chicory, have
      also been studied. The possibility to characterize their presence in coffee
      extracts was evaluated.

PMID- 17444225
TI  - Retention indices in the analysis of food aroma volatile compounds in temperature
      programmed gas chromatography: database creation and evaluation of precision and
      robustness.
AB  - A retention index (RI) database containing 250 volatile compounds was created on
      a polar stationary phase column and validated for food aroma characterisation.
      Precision of the retention indices (RIs) was assessed by performing replicated
      injections of a representative number of volatiles under the same experimental
      conditions: differences lower than 1 U were observed for all the compounds.
      Robustness was evaluated by carrying out injections of the same set of volatile
      compounds under different experimental conditions, i.e. program temperature,
      column batches and instrumentation. Excellent results were obtained with a
      maximum difference in the RI values of 10 U. The capabilities of the created
      database for food aroma characterisation were finally evaluated by analysing the
      volatile fractions of different food matrices such as dry sausages, cheese and
      bread. A great number of volatile compounds were identified in the analysed
      samples on the basis of their RI, thus proving the usefulness of the RI
      collections in the field of food analysis.

PMID- 17444226
TI  - Headspace liquid phase microextraction for quantitation of hexanal in potato
      crisps by gas chromatography.
AB  - A simple and rapid method using headspace liquid-phase microextraction (HS-LPME)
      was developed for the determination of hexanal at low levels in potato crisp
      samples. Parameters such as extraction solvent, agitation of the sample, salt
      addition, organic drop volume, exposure time, and extraction time were controlled
      and optimised. The developed protocol was found to yield a linear calibration
      curve in the concentration range from 0.001 to 2 mg/L and a limit of detection of
      0.1 microg/L with a good enrichment factor of > 107 for the analyte. The
      repeatability of the method was satisfactory (4%). The results demonstrate that
      HS-LPME is a rapid, accurate, and effective preparation method and could be
      successfully used for the determination of hexanal in potato crisp samples.

PMID- 17444227
TI  - A simple capillary gel electrophoresis approach for efficient and reproducible
      DNA separations. Analysis of genetically modified soy and maize.
AB  - It is generally assumed that in order to achieve suitable separations of DNA
      fragments, capillary gel electrophoresis (CGE)-coated capillaries should be used.
      In this work, a new method is presented that allows to obtain reproducible CGE
      separations of DNA fragments using bare fused-silica capillaries without any
      previous coating step. The proposed method only requires: (i) a capillary washing
      with 0.1 M hydrochloric acid between injections and (ii) a running buffer
      composed of Tris-phosphate-ethylenediamine tetraacetic acid (EDTA) and 4.5% of 2
      hydroxyethyl cellulose (HEC) as sieving polymer. The use of this new CGE
      procedure gives highly resolved and reproducible separations of DNA fragments
      ranging from 50 to 750 bp. The separation of these DNA fragments is accomplished
      in less than 30 min with efficiencies up to 1.7 x 10(6) plates/m. Reproducibility
      values of migration times (given as %RSD) for the analyzed DNA fragments are
      better than 1.0% (n = 4) for the same day, 2.2% (n = 16) for four different days,
      and 2.3% (n = 16) for four different capillaries. The usefulness of this
      separation method is demonstrated by detecting genetically modified maize and
      genetically modified soy after DNA amplification by PCR. This new CGE procedure
      together with LIF as detector provides sensitive analysis of 0.9% of Bt11 maize,
      Mon810 maize, and Roundup Ready soy in flours with S/ N up to 542. These results
      demonstrate the usefulness of this procedure to fulfill the European regulation
      on detection of genetically modified organisms in foods.

PMID- 17444228
TI  - Comparative evaluation of extraction procedures and method validation for
      determination of carbohydrates in cereals and dairy products by capillary
      electrophoresis.
AB  - This work describes the development and application of two optimized
      electrolytes: 15 mmol/L sorbate, 0.2 mmol/L CTAB, and 35 mmol/L sodium hydroxide
      for the determination of fructose, glucose, maltose, maltotriose, and sucrose in
      cereals and 15 mmol/L sorbate, 0.3 mmol/L CTAB, and 55 mmol/L sodium hydroxide
      for the determination of fructose, glucose, galactose, lactose, and sucrose in
      dairy products. Both methods were validated with respect to linearity, limits of
      detection (using both signal-to-noise ratio and the Eurachem approach), recovery
      tests, and intra- and inter-day precision exhibiting adequate performance.
      Additionally, statistically similar results were obtained in a comparative study
      of extraction procedures for carbohydrates using the AOAC protocol, ultrasound
      extraction, magnetic stirring, and sample dissolution.

PMID- 17444229
TI  - Antioxidant compounds of propolis determined by capillary electrophoresis-mass
      spectrometry.
AB  - Propolis is a resinous hive product rich in antioxidant compounds. Capillary
      electrophoresis coupled to mass spectrometric detection can provide selective
      information about the analytes present in complex extracts of propolis and has
      turned out to be an attractive alternative to HPLC methods. Therefore, a CE-ESI
      MS method has been developed for the analysis of antioxidant compounds obtained
      from propolis. For this purpose, different electrophoretic parameters such as the
      nature, pH, and concentration of the separation buffer, as well as electrospray
      parameters (dry gas temperature and flow, nebulising gas pressure, and make-up
      flow) have been carefully optimised. Different phenolic compounds (e.g.
      pinobanksin 3-acetate, naringenin, pinocembrin, chrysin, daidzein, quercetin 3',7
      dimethyl ether, apigenin, and kaempferid) could be detected. To confirm the
      identity of the phenolic compounds in propolis extracts, accurate mass data of
      the molecular ions were obtained by TOF MS. Limits of detection ranging from 6
      mg/100 g of raw propolis for chrysin to 58 mg/ 100 g of raw propolis for
      luteolin, were obtained.

PMID- 17444230
TI  - Compositional changes induced by UV-B radiation treatment of common bean and
      soybean seedlings monitored by capillary electrophoresis with diode array
      detection.
AB  - In this work, a new CE method with diode array detection (DAD) was developed for
      the monitoring and quantitation of flavonoids in different beans treated and
      untreated with UV-B radiation. Flavonoid concentration was monitored in UV-B
      treated and untreated sprouts of three common beans (Zolfino ecotype, cv.
      Verdone, cv. Lingua di Fuoco) and one soybean (cv. Pacific). After acid
      hydrolysis of extracts, the CE-DAD method provides reproducible quantitative
      determinations of daidzein, glycitein, genistein, and kaempferol at ppm level in
      these natural matrices within a relatively short time (less than 16 min). Total
      flavonoid content determined by CE-DAD was 159 +/- 8, 26 +/- 2, 13 +/- 1, and 1.3
      +/- 0.3 microg/g fresh weight for untreated sprouts of Pacific soybean, Verdone
      bean, Zolfino bean, and Lingua di Fuoco bean, respectively. UV-B treatment caused
      no significant quantitative effect on Pacific soybean sprouts, whereas it
      enhanced the total isoflavone content by 1.5, 1.8, and 3.2-fold in Verdone,
      Zolfino, and Lingua di Fuoco beans, respectively. The proposed method shows (i)
      the potentialities of bean sprouts as a natural source of bioactive compounds
      (antioxidants); (ii) the technological role of UV-B treatment for sprout
      isoflavone enrichment; and (iii) the good capabilities of CE-DAD to monitor this
      process.

PMID- 17444231
TI  - Analysis of aromatic and terpenic constituents of pepper extracts by capillary
      electrochromatography.
AB  - An original method based on CEC has been developed for the determination of
      aromatic and terpenic compounds in extracts of spices obtained from Piper nigrum.
      The method is based on the use of a fused silica capillary (effective length:
      23.5 cm, internal diameter: 100 microm) packed with a C18 sorbent (packing
      length: 23 cm, particle size: 5 microm). The mobile phase is a 50 mM, pH 6.0
      ammonium acetate/ACN (10:90 v/v) mixture. Applying a 30 kV voltage, the following
      11 compounds were separated and analysed: terpinen-4-ol, caryophyllene oxide,
      limonene, alpha-pinene, 3-carene, beta-pinene, alpha-humulene, beta
      caryophyllene, alpha-phellandrene, eugenol and piperine. Compound determination
      is carried out using a diode-array detector set at 265 and 338 nm for alpha
      phellandrene and piperine, respectively, and at 210 nm (reference subtraction at
      282 nm) for all the other analytes. The optimised method has been validated with
      good results in terms of linearity, limits of quantitation, detection and
      precision. The CEC method was successfully applied to the analysis of essential
      oils and methanolic extracts of 'black', 'white' and 'green' pepper.

PMID- 17444232
TI  - Evaluation of the QuEChERS sample preparation approach for the analysis of
      pesticide residues in olives.
AB  - This paper describes the use of a quick, easy, cheap, effective, rugged, and safe
      (QuEChERS) method for extraction and cleanup of 16 pesticide residues of interest
      in olives and olive oil. These products contain a high lipid content, which can
      adversely affect pesticide recoveries and harm traditional chromatographic
      systems. For extraction, the main factors (oil and water content) were studied
      and optimized in experiments to maximize pesticide recoveries. Dispersive SPE
      with different sorbents was also investigated to minimize matrix coextractives
      and interferences. For analysis, a new automated DSI device was tested in GC-MS
      to avoid nonvolatile coextractives from contaminating the instrument. LC-MS/MS
      with positive ESI was used for those pesticides that were difficult to detect by
      GC-MS. The final method was validated for olives in terms of recoveries,
      repeatabilities, and reproducibilities using both detection techniques. The
      results demonstrated that the method achieved acceptable quantitative recoveries
      of 70-109% with RSDs < 20% for DSI-GC-MS and 88-130% with RSDs < 10% for LC
      MS/MS, and LOQ at or below the regulatory maximum residue limits for the
      pesticides were achieved.

PMID- 17444233
TI  - A weekly dose of recovery information.

PMID- 17444234
TI  - Focusing on integration.

PMID- 17444235
TI  - Emphasizing best practices.

PMID- 17444236
TI  - Refining requirements.

PMID- 17444237
TI  - Ensuring quality and safety.

PMID- 17444238
TI  - Why not accreditation?

PMID- 17444239
TI  - Getting to 'yes in my backyard'.

PMID- 17444240
TI  - Become an employer of choice.

PMID- 17444241
TI  - Not resting on ITs laurels. Interview by Michael Levin-Epstein.

PMID- 17444242
TI  - The EHR was just the beginning.

PMID- 17444244
TI  - Careers based on personal experience.

PMID- 17444243
TI  - Technology that informs treatment.

PMID- 17444245
TI  - Learning from history.

PMID- 17444246
TI  - Making data analysis easier.
AB  - There has been a break-through in data analysis tools, and information now can be
      delivered in usable formats that contribute to decision making. These new tools
      make use of the volume of data and the length of data history now accumulating in
      behavioral health information systems. These tools can help bring data-driven,
      evidence-based, 21st-century decision support to behavioral healthcare.

PMID- 17444248
TI  - Time to be transparent and accountable.

PMID- 17444247
TI  - Our need for 'general contractors'.

PMID- 17444249
TI  - The morbidity of psoriatic disease.
AB  - There is a considerable area of intersection between the negative consequences of
      psoriatic skin inflammation and the negative consequences of psoriatic joint
      inflammation. However, available evidence indicates that PsA also has a unique
      set of possible undesirable outcomes, such as severe disability and increased
      mortality, that are particularly serious. In light of this evidence, it has
      become increasingly clear that PsA is not the relatively mild condition it was
      once believed to be, but rather a disease that can have a dramatic negative
      impact on affected patients.

PMID- 17444250
TI  - Diagnostic signs and symptoms of psoriatic arthritis.
AB  - PsA is a distinct pathologic entity with a unique set of diagnostically relevant
      clinical features. The typical clinical picture of PsA consists of peripheral
      joint inflammation with an asymmetric pattern of involvement. Furthermore, other
      clinical signs, such as sacroiliitis, enthesitis, dactylitis, and nail lesions,
      are also closely associated with the disease. By gaining familiarity with the
      features of PsA, as well as the ways in which disease presentation may vary,
      health care professionals will be better equipped to identify this condition,
      making early treatment, which is an essential step toward optimizing patient
      outcomes, more readily achievable.

PMID- 17444251
TI  - The rheumatology/dermatology collaboration.
AB  - Psoriatic arthritis (PsA) of often has a destructive course, characterized by
      progressive damage to bone and joints. Consequently, prompt detection is
      critical, allowing effective, disease-modifying treatment to be administered at
      the earliest possible point in the progression of the disease. The collaboration
      between dermatologic and rheumatologic professionals in the early diagnosis, and
      subsequent management, of PsA is explored, with a focus on case studies that
      illustrate the potentialfor such collaboration.

PMID- 17444252
TI  - On teaching moral reasoning.

PMID- 17444253
TI  - History of water fluoridation and the ubiquity of fluoride in our environment.

PMID- 17444254
TI  - Affordable care today, not a world away.

PMID- 17444255
TI  - Oral pathology quiz # 54. Case number 1. Ameloblastoma.

PMID- 17444256
TI  - Oral pathology quiz # 54. Case number 2. Amalgam tattoo.

PMID- 17444257
TI  - Oroantral communication with chronic sinusitis 8 years after maxillofacial
      trauma: a case report.

PMID- 17444258
TI  - Someone to lend a hand when you're hurting.

PMID- 17444259
TI  - Factor V Leiden--dental patient management for a rare bleeding disorder: a case
      report.
AB  - In today's complex healthcare environment, there is an increasing incidence of
      patients with serious medical issues who may present for dental care. Excessive
      post-operative bleeding is always a concern of the dentist. It is essential that
      the contemporary oral healthcare provider be familiar with: 1. The basics of
      bleeding and coagulation; 2. the medications that can affect these processes; 3.
      published guidelines which provide the framework for patient evaluation and
      management; and 4. adjunctive procedures necessary to control post-treatment
      bleeding.

PMID- 17444260
TI  - Advocates, legislators gear up for battle in the fight to keep genetic
      information, testing secure from employers, insurers.
AB  - A 12-year deadlock over genetic discrimination is set to be broken in Congress.
      Scientists and patient advocates welcome the news, but employers and insurers
      call the legislation premature and say it could cause administrative hassles.
      "It's a remedy in search of a cause", says Burton Fishman, left, an attorney for
      business interests. "We think it's really based on the politics of fear and
      anecdote, and not on reality.

PMID- 17444261
TI  - Whistle-blower law tightened. Ruling demands first-hand knowledge of wrongdoing.

PMID- 17444262
TI  - Highmark, Independence join merger frenzy. Pa. Blues deal OK could take two
      years; insurer would control half of state's market.

PMID- 17444263
TI  - HealthSouth deals again. TPG to buy outpatient surgery centers for $920 million.

PMID- 17444264
TI  - Far-flung ERs. Fla. weighs oversight of satellite emergency departments.

PMID- 17444265
TI  - Front-runners run from specifics. Edwards, Romney may be trailing the overall
      race, but they lead on healthcare.

PMID- 17444266
TI  - It's time for mental health parity. Congress set to pass some form of measure to
      redress disparities in coverage.

PMID- 17444267
TI  - A view from the top...shows exiting association executives among those making the
      most, in Modern Healthcare's latest compensation survey.

PMID- 17444268
TI  - Owners' manual. With for-profits, the great unknown is who the primary investors
      are.

PMID- 17444269
TI  - CON request blocked. Rivals foil Mo. specialty hospital plan.

PMID- 17444270
TI  - Straighttalk. The ideal master facility plan begins with business strategy and
      integrates operational improvement.
AB  - Given the scarcity of capital to meet ever-growing demands for healthcare
      services, master facility planning has become more important than ever.
      Executives must align their master facility plans with their overall business
      strategy, incorporating the best in care- and service-delivery models. In this
      installment of Straight Talk, executives from two health systems--Advocate Health
      Care in Oak Brook, Ill. and Parkland Health & Hospital System in Dallas--discuss
      master facility planning. Modern Healthcare and PricewaterhouseCoopers present
      Straight Talk. The session on master facility planning was held on March 8, 2007
      at Modern Healthcare's Chicago Headquarters. Charles Lauer, former vice president
      of publishing and editorial director at Modern Healthcare, was the moderator.

PMID- 17444271
TI  - Biography of Sandor von Koranyi.

PMID- 17444272
TI  - Renin-angiotensin system affects endothelial morphology and permeability of renal
      afferent arteriole.
AB  - The afferent arteriole (AA) is an important regulatory site of renal function and
      blood pressure. We have demonstrated endothelial fenestration and high
      permeability in the vicinity of renin granulated epithelioid cells in the
      juxtaglomerular portion of the afferent arteriole in different mammals. The
      permeability of fenestrated endothelium of afferent arteriole may be important in
      connection to various physiologic and pathophysiologic processes. We have assumed
      that the permeable fenestration may serve as a communication channel between the
      intravascular circulation and a pathway for renin secretion. Utilising the
      multiphoton image technique we were able to visualise the endothelial
      fenestration and renin granules of the in vitro microperfused AA and in vivo AA.
      We demonstrated that ferritin-positive, i.e., permeable portion of the afferent
      arteriole, under control conditions is on average 45 microm, which is about one
      third to half of the total length of the afferent arteriole. The length of this
      portion is not constant and can change by physiologic and pharmacologic
      manipulation of renin formation. The permeability of the afferent arteriole is
      not changing only parallel with the pharmacologically stimulated renin secretion
      as already demonstrated in adult rats, but also with the change of renin
      appearance in afferent arteriole within the very first few days of life after
      birth. Independently from the age there is a significant correlation between the
      renin-positive and permeable portion of the AA. Further studies are necessary to
      clarify the physiological significance of afferent arteriolar permeability and
      its changes in the postnatal development of the kidney, as well as in correlation
      with activity of renin- angiotensin system.

PMID- 17444273
TI  - Angiotensin II activates plasminogen activator inhibitor-I promoter in renal
      tubular epithelial cells via the AT1 receptor.
AB  - BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) regulates normal
      extracellular matrix (ECM) metabolism and it is a key regulator of the fibrotic
      process. Both angiotensin II (Ang II) and angiotensin IV (Ang IV) have been
      reported to stimulate PAI-1 expression. It is not known how PAI-1 expression is
      regulated by the renin-angiotensin system (RAS) in renal tubular cells. METHODS:
      To dissect signaling mechanisms contributing to the up-regulation of the PAI-1
      promoter, porcine proximal tubular cells stably expressing the rabbit AT1
      receptor (LLC-PK/AT1) were transiently transfected with a luciferase reporter
      construct containing the PAI-1 promoter. Promoter activation was assessed by
      measuring luciferase activity from cell lysates. RESULTS: Ang II dose-dependently
      stimulated the transcriptional activity of the PAI-1 promoter in renal proximal
      tubular cells whereas Ang IV had no consistent effect on the promoter activity.
      Neither inhibition of the Extracellular Signal Regulated Kinase (ERK) cascade nor
      inhibition of the c-Jun-N-terminal Kinase (JNK) pathway did reduce the
      stimulation of the PAI-1 promoter by Ang II. However, genistein, a tyrosine
      kinase inhibitor blocked the effect of Ang II. CONCLUSION: Ang II but not Ang IV
      activates the PAI-1 promoter in renal proximal tubular cells and this effect is
      mediated by tyrosine kinases.

PMID- 17444274
TI  - Intrarenal renin-angiotensin system and counteracting protective mechanisms in
      angiotensin II-dependent hypertension.
AB  - It is now well accepted that alterations in kidney function, due either to
      primary renal disease or to inappropriate hormonal influences on the kidney, are
      a cardinal characteristic in all forms of hypertension, and lead to a reduced
      ability of the kidneys to excrete sodium and the consequent development of
      elevated arterial pressures. However, it is also apparent that many extrarenal
      factors are important contributors to altered kidney function and hypertension.
      Central to many hypertensinogenic processes is the inappropriate activation of
      the renin-angiotensin system (RAS) and its downstream consequences by various
      pathophysiologic mechanisms. There may also be derangements in arachidonic acid
      metabolites, endothelium derived factors such as nitric oxide and carbon
      monoxide, and various paracrine and neural systems that normally interact with or
      provide a counteracting balance to the actions of the RAS. Thus, when the
      capacity of the kidneys to maintain sodium balance and extracellular fluid volume
      within appropriate ranges is compromised, increases in arterial pressure become
      necessary to re-establish normal balance.

PMID- 17444275
TI  - Endothelin-1 gene and endothelial nitric oxide synthase gene polymorphisms in
      adolescents with juvenile and obesity-associated hypertension.
AB  - Hypertension is an increasing public health problem all over the world. Essential
      hypertension accounts for more than 90% of cases of hypertension. It is a complex
      genetic, environmental and demographic trait. New method in molecular biology has
      been proposed a number of candidate genes, but the linkage or association with
      hypertension has been problematic (lack of gene-gene and gene-environment
      interaction). It is well known that genetic influences are more important in
      younger hypertensives, because children are relatively free from the common
      environmental factors contributing to essential hypertension. The association
      studies compare genotype ferquencies of the candidate gene between patient groups
      and the controls, in pathways known to be involved in blood pressure regulation.
      This study examined three polymorphisms of these factors encoding genes (ET-1
      G+5665T (Lys198Asn), endothelial nitric oxide synthase (eNOS) T-786C promoter
      polymorphism and 27-bp repeat polymorphism in intron 4) in adolescents with
      juvenile essential and obesity-associated hypertension. Significant differences
      were found in the G/T genotype of the ET-1 polymorphism in the hypertensive and
      obese+hypertensive patients (body mass index (BMI) > 30). A strong association
      was detected between the BMI and the polymorphism of the ET-1 gene. It seems that
      ET-1 gene polymorphism plays a role in the development of juvenile hypertension
      associated with obesity. Although no significant differences were seen in the
      case of the eNOS promoter polymorphism and the eNOS 4th intron 27-bp repeat
      polymorphism. It seems that eNOS may play a role, but this is not the main factor
      in the control of blood pressure; it is rather a fine regulator in this process.
      This study with adolescents facilitates an understanding of the genetic factors
      promoting juvenile hypertension and obesity.

PMID- 17444276
TI  - Chemokines and chemokine receptors in renal transplantation--from bench to
      bedside.
AB  - Attraction of mononuclear cells to sites of inflammation requires a close
      interplay of the inflammatory signal presented via chemokines and specific
      receptors on effector cells. First studies on acute renal transplant rejection
      demonstrated the involvement of CC-chemokines, such as RANTES, MIP-1alpha, MIP
      1beta and MCP-1, as well as CXC-chemokines such as IL-8 and IP-10, correlating
      with expression of the corresponding chemokine receptors, CCR1, CCR5 and CCR2 as
      well as CXCR3. Since then, the pathophysiologic relevance has been extended to
      chronic allograft nephropathy and transplant glomerulopathy. Chemokine expression
      can be triggered by different stimuli, e.g. brain death, ischemia, HLA-mismatch
      and infection. Furthermore, anti-inflammatory chemokines have been identified.
      Chemokine receptor 7, e.g. enhances homing of lymphocytes to lymphatic tissues
      and the Duffy antigen receptor, DARC, a non-specific receptor that binds and
      inactivates different chemokines. While measurement of chemokine expression in
      clinical transplantation may facilitate the differential diagnosis of allograft
      dysfunction, knowledge of the chemokine network has also widened the
      understanding of transplant rejection and opened novel therapeutic approaches.
      Observations from humans with mutations of the chemokine network as well as
      transplantation of animals with targeted deletions in this system suggest that
      manipulations of chemokine signalling may improve the success rates of
      transplantation. Blocking chemokines unselectively with Met-RANTES or
      specifically with small molecule inhibitors of various chemokine receptors has
      lead to improved outcome in animal models. Currently, first human trials are
      under way to investigate drugs that stimulate lymphocyte homing. Inhibitors of
      CCR1 and CCR5 are being tested for other human diseases and may eventually be
      available in transplantation. Nonetheless, chemokine blockade my rather serve as
      an adjunct in the management of transplant recipients than a new "magic bullet".

PMID- 17444277
TI  - Coordination of kidney filtration and tubular reabsorption: considerations on the
      regulation of metabolic demand for tubular reabsorption.
AB  - Kidney blood flow is highly regulated by a combination of myogenic
      autoregulation, multiple neurohormonal systems and the tubuloglomerular feedback
      system, the later of which specifically relates tubular reabsorption to the
      filtered load. Oxygen and substrate requirements of the kidney are dictated by
      both supply of oxygen and substrates and metabolic demands of the kidney. The
      tubuloglomerular feedback system utilizes mediators which are intimately linked
      to cellular metabolism, ATP and adenosine. This system based upon communication
      transfer between the macular densa and the afferent arteriole stabilizes kidney
      function and is not static but temporally adapts or resets to new external
      physiologic conditions. Such temporal adaptation occurs via modulators such as
      nitric oxide (NO), primarily derived from NOS-1, angiotensin II and COX-2
      products. These hormonal influences also exert capacities to modulate cellular
      demands for oxygen, particularly NO which decreases oxygen consumption via
      multiple mechanisms. The several mechanisms whereby NO and other hormonal systems
      and transporter activity can regulate and produce changes in kidney metabolic
      demands are discussed. Modulators which influence temporal adaptation and
      resetting of TGF are also significant contributors to the regulation of cellular
      oxygen consumption in the kidney. These systems may act in concert to preserve
      the coordination of filtered load and tubular reabsorption and the metabolic
      demands of kidney function, thereby determining the ischemic threshold for kidney
      function.

PMID- 17444278
TI  - Iron homeostasis in chronic inflammation.
AB  - Inflammation induced anemia and resistance to erythropoietin are common features
      in patients with chronic kidney disease (CKD). Elevated levels of cytokines and
      enhanced oxidative stress, conditions associated with inflammatory states, are
      implicated in the development of anemia. Accumulating evidence suggests that
      activation of cytokine cascade and the associated acute-phase response, as it
      often occurs in patients with CKD, divert iron from erythropoiesis to storage
      sites within the reticuloendothelial system leading to functional iron deficiency
      and subsequently to anemia or resistance to erythropoietin. Other processes have
      also been shown to be involved in the pathogenesis of anemia provoked by the
      activated immune system including an inhibition of erythroid progenitor
      proliferation and differentiation, a suppression of erythropoietin production and
      a blunted response to erythropoietin. The present review concerns the underlying
      alterations in iron metabolism induced by chronic inflammation that result in
      anemia.

PMID- 17444279
TI  - The aging kidney: role of endothelial oxidative stress and inflammation.
AB  - The population in the Western world is aging. In 1996 those aged 60 years and
      over formed 21% of the EU population, by 2022 this proportion will have risen to
      27%. Based on current trends a third of the EU population could be 60 years of
      age and over by the age 2050. Epidemiological studies suggest that even in the
      absence of other risk factors (e.g. diabetes, hypertension,
      hypercholesterolemia), advanced age itself significantly increases cardiovascular
      morbidity by promoting the development of atherosclerosis and by impairing normal
      cellular functions. One of the most prominent organs affected by aging is the
      kidney. There is evidence that age-associated phenotypic changes may be an
      important cause of renal failure. We propose that vascular oxidative stress and
      inflammation are generalized phenomena during senescence, which importantly
      contribute to the morphological and functional changes in the aging kidney. The
      present review focuses on some of the mechanisms by which advanced age may
      promote vascular oxidative and nitrosative stress and the possible downstream
      mechanisms by which reactive oxygen and nitrogen species may impair vascular and
      renal function in aging.

PMID- 17444280
TI  - Epithelial-mesenchymal transition in renal tubular cells in the pathogenesis of
      progressive tubulo-interstitial fibrosis.
AB  - Epithelial-mesenchymal transition (EMT) plays an important role in embryogenesis
      and organ formation. Over the last 10-15 years it has been established that EMT
      is a significant mechanism of tumor progression and metastasis formation and also
      of progressive tissue fibrosis in the kidney, liver and lung. EMT seen in these
      diverse physiological and pathophysiological contexts shares a number of stages
      and modules, but also carries distinct, context specific characteristics. EMT in
      tissue fibrosis is a form of reverse embryogenesis, when highly specialized
      epithelial cells in the specific organs will respond to injury with loosing their
      epithelial characteristics and functions and regaining characteristics of the
      cells from which they originated. EMT in the context of tissue fibrosis can be
      induced by different forms of injury or a set of humoral factors. The process is
      regulated by a complex balance of humoral and microenvironmental stimuli, in
      which cell-cell contacts and interaction of the transitioning cell with the
      extracellular matrix components is very important. Intense research in this
      exciting field yielded good understanding of many of the details of this
      fascinating process, although numerous questions still await proper answers.
      There is indication that understanding of the molecular mechanisms underlying
      "fibrotic" EMT may lead to the design of specific and effective therapeutic
      measures for progressive tissue fibrosis.

PMID- 17444281
TI  - Urine proteomics--prospects for future diagnostics.
AB  - This brief overview of the potential diagnostic, prognostic and
      pathophysiological value of studies into the urine proteome describes hypothesis
      driven investigations of individual proteins and proteome-wide search for urinary
      biomarkers of various diseases and their progression. It is intended to
      illustrate the recent progress in the area of urine proteomics and proselytize
      for the promise of this centuries-old technique of uroscopy, yet to reveal its
      secrets, using modem approaches.

PMID- 17444282
TI  - Renal extraction of circulating adiponectin in patients with renovascular
      hypertension.
AB  - BACKGROUND: Patients with chronic renal failure are characterized by an elevated
      plasma adiponectin concentration, which is significantly lowered after successful
      kidney transplantation. The direct renal clearance and extraction of adiponectin
      have not yet been documented in humans. Therefore the aim of the study was to
      estimate separate kidney extraction of adiponectin, by measuring its
      concentration in the aorta and both renal veins, in patients with renovascular
      hypertension caused by unilateral renal artery stenosis. METHODS: In 30 patients
      with significant (> 70%) unilateral renal artery stenosis, plasma adiponectin was
      measured in blood samples taken from the aorta, both renal veins and the vena
      cava inferior below the orifices of the renal veins. RESULTS: Renal venous plasma
      adiponectin concentrations (both from the kidney with renal artery stenosis and
      from the contralateral organ) were only numerically lower than the concentrations
      measured in the aorta (11.10 [8.65-13.56]; 11.12 [8.81-13.42]; 11.35 [8.90-13.80]
      microg/ml, respectively). Fractional extraction of adiponectin was 5.0 [-1.6
      11.0]% in the kidney with renal artery stenosis and 3.0 [-2.4-9.01% in the
      contralateral "normal" kidney. Slightly higher concentrations of plasma
      adiponectin were observed in the vena cava inferior below the orifices of the
      renal veins (11.79 [9.14-14.44] microg/ml). In patients with unilateral renal
      artery stenosis significant negative correlations were found between plasma
      adiponectin concentration obtained from the vena cava inferior below the orifices
      of renal veins and eGFR (r = -0.38; p < 0.05), systolic (r = -0.71; p < 0.0001)
      and diastolic blood pressure (r = -0.40; p < 0.04), as well as serum triglyceride
      concentrations (r = -0.64; p < 0.001). CONCLUSION: The findings indicate that the
      fractional renal extraction of adiponectin is rather low.

PMID- 17444283
TI  - Obesity and adiponectin after kidney transplantation.
AB  - Obesity and hyperlipidaemia are found very frequently after kidney
      transplantation (Tx) and may represent independent risk factors for development
      of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic
      study, we monitored, a total of 68 obese transplant patients [body mass index
      (BMI) > 30 kg/m2] with dyslipidaemia over a period of 24 months. We compared the
      findings of a new therapeutic regimen 1 year (start of the study) and 2 years
      after renal transplantation. Based on a Subjective Global Assessment Scoring
      Sheet, we started at the end of the first year with an individualized hypoenergic
      hypolipidaemic diet (IHHD). Subsequently, after corticoid withdrawal, IHHD was
      supplemented regularly with statins (atorvastatin 10-20 mg/day)) and followed-up
      for 2 years. All patients were on a regimen of cyclosporin A or tacrolimus and
      mycophenolate mofetil. During the study period, there was a significant decrease
      in BMI (p < 0.025) and an increase of the adiponectin level (p < 0.01). Long-term
      therapy was associated with a significant decrease in serum leptin (p < 0.01) and
      lipid metabolism parameters (p < 0.01). Inulin clearance, mean systolic and
      diastolic blood pressure, proteinuria, lipoprotein(a) and apo-lipoprotein E
      isoforms did not differ significantly. Based on our results, we assume that
      obesity and hyperlipidaemia after renal transplantation can be treated
      effectively by modified immunosuppression (corticosteroid withdrawal), statins
      and long-term diet (IHHD). The increased level of adiponectin may be a marker of
      reducing atherosclerotic and chronic allograft nephropathy processes.

PMID- 17444284
TI  - Single dose of acetylsalicylic acid in patients with Type 2 diabetes mellitus
      and/or chronic renal failure ameliorates anaemia by decreasing the rate of
      neocytolysis.
AB  - BACKGROUND: Anaemia in diabetes mellitus (DM) and/or chronic renal failure (CRF)
      may be caused by a decreased production of erythropoietin (EPO), EPO resistance,
      and by the lysis of the young circulating red blood cells (neocytolysis) induced
      by subclinical inflammation and low EPO level. Aims of this study were to detect
      EPO resistance in patients with DM and/or CRF and to prove, that acetylsalicylic
      acid (ASA) is able to improve the haemopoietic status by decreasing neocytolysis.
      METHODS: In a cross-sectional study, three groups of selected patients (patients
      with DM; patients with DM+CRF; patients with CRF without DM, n=15 each) and a
      group of controls (non-diabetic, nonazotemic subjects, n = 10) were compared. In
      the intervention part of the study, the effect of a single dose of 1 gram ASA on
      neocytolysis was investigated in a subgroup of these patients. RESULTS: Despite
      the similar EPO level (p = 1.000), all three patient groups had lower haemoglobin
      and haematocrit than control persons (p < 0.05 in all cases). Patients with
      DM+CRF had lower haemoglobin than patients with DM or CRF alone (p < 0.05).
      Single dose of ASA induced a fast increase in serum EPO level, a concomitant rise
      of the Rtc number and rate, red blood cell count, haematocrit and haemoglobin p <
      0.01 for each). These changes were accompanied by a marked decrease in serum
      lactate dehydrogenase activity (p < 0.01). CONCLUSIONS: DM and CRF may induce
      erythropoietin resistance. In these patients, ASA treatment increases serum EPO
      level. The higher EPO level and the anti-inflammatory effect of ASA may decrease
      neocytolysis.

PMID- 17444285
TI  - [Psychopathology and creativity].
AB  - In this paper, a concept has been presented stating that the process of
      creativity may be connected with psychopathological features such as mood
      disorders, mainly bipolar, and psychosis-like thought abnormalities. Biographic
      studies point to a more frequent occurrence of affective disorders in creative
      subjects and members of their families. There is also data concerning the
      occurrence of schizophrenia in the families of prominent persons. A number of
      studies have demonstrated a similarity of patients with bipolar affective illness
      and members of their families to creative persons, as to increased indexes of
      creativity as well as such temperamental features as cyclothymia, neuroticism and
      openness. An association has been also found between the dimension
      of"psychoticism", schizotypal features and the measures of creativity. A
      reduction of the so called "latent inhibition" mechanism, resulting in perception
      of seemingly irrelevant external stimuli is connected with a predisposition to
      both increased creativity and schizophrenia-like disturbances. A neurobiological
      model of generating ideas and creative drive assumes a dominant role of three
      brain structures: frontal lobes, temporal lobes and the mesolimbic system. The
      neurotransmission system mostly connected with elevated mood and psychotic
      thinking is the dopaminergic system, especially its mesolimbic and cortical
      pathways. Both neurobiological and pharmacological evidence has been accumulated
      for an association of these pathways with motivational, emotional and cognitive
      processes, and indirectly, with the processes of creativity. In recent years, a
      number of interesting results has also been obtained from molecular-genetic
      studies about genetic determinants of creativity processes in association with
      bipolar mood changes and psychotic conditions.

PMID- 17444286
TI  - [Cognitive inhibition and thought suppression in obsessive-compulsive disorder--a
      review].
AB  - The symptoms of obsessive-compulsive disorder (OCD)--repetitive troublesome
      intrusive thoughts and/or compulsions--may indicate a reduction in the efficiency
      of inhibitory control over thought and action. A number of neuropsychological
      studies using various indices of inhibitory activity were aimed at verifying the
      hypothesis of deficient inhibition in OCD. The paper critically reviews the
      studies that relate to three kinds of inhibition-related phenomena --i.e.
      negative priming, thought suppression, and directed forgetting--and summarises
      the results of other research addressing the inhibitory processes in OCD
      subjects. All in all, the results do not support the hypothesis of general
      inhibitory deficit in OCD, although some studies suggest an impairment in the
      ability to suppress specific mental contents in this clinical group. In the
      discussion some general problems related to neuropsychological diagnosis of
      inhibitory processes in psychopathology are indicated.

PMID- 17444288
TI  - [Level of anxiety and self-image in patients with coronary heart disease].
AB  - AIM: The aim of the article was to find the relationship between the level of
      anxiety and self-image in patients with coronary heart disease. METHODS: Subjects
      were 70 patients with stable coronary heart disease treated in the Internal
      Medicine Department of the Military Hospital in Lublin and 70 healthy controls.
      Mean age of the investigated patients was 53.11 years with the mean age in
      healthy controls being 50.1 years. Subjects were investigated with the use of
      Spielberg's State-Trait Anxiety Inventory (STAI), Adjective Check List (ACL) and
      a questionnaire especially designed for the study concerning the socio
      demographic data of the investigated patients. RESULTS: Our results showed a
      statistically significant higher level of anxiety in men with coronary heart
      disease as compared to a group of healthy control men. Level of anxiety in women
      with coronary heart disease compared with healthy control women did not differ
      significantly. We found a statistically significant relationship between the
      elevated level of anxiety and certain features of self-image. CONCLUSIONS: 1. Men
      with coronary heart disease exhibit a higher level of anxiety compared with
      healthy men. 2. Higher level of anxiety in men is associated with the increased
      need of stabilization, withdrawal from achieving aims, lack of self-trust and
      lack of autonomy. 3. High level of anxiety in women is associated with negative
      self-assessment, lack of self-trust, tendency for isolation and stronger need of
      changes.

PMID- 17444287
TI  - [Gabapentin (GBP) in panic disorders--case report].
AB  - Gabapentin is an anticonvulsant structurally similar to gamma - amino- butyric
      acid considered as the central acting GABA- analogue. It is used mostly as an
      antiepileptic agent. A constantly growing number of studies refer to its efficacy
      in the treatment of psychiatric disorders. AIM: To audit the effectiveness of the
      gabapentin used as adjunctive treatment of intensified panic disorder. MATERIAL:
      6 patients (5 women, 1 man, of mean age 44.2 years) treated with gabapentin in
      combined therapy of a mean dose 300 mg/d, lasting on average 196 days. METHOD:
      Patients were diagnosed using research criteria based on the ICD-10 and
      M.I.N.I.5.0.0. RESULTS AND CONCLUSION: Adverse events were not observed and an
      addition of gabapentin into treatment brings improvement of the clinical
      condition. Complete amelioration was detected in 4 of the 6 patients. In one
      single year of observation panic disorder relapses were not observed even though
      there was a discontinuation of treatment. The presented case reports show a
      possibility of successful treatment with gabapentin in severe panic disorders.

PMID- 17444289
TI  - [Difficult asthma and gender of patients versus the presence of profound
      psychological trauma].
AB  - BACKGROUND: The authors examined psychiatrically a group of 97 patients suffering
      from severe asthma (classified according to GINA 2002). The special interest of
      the study was the careful analyse the time, context and content of different
      psychological traumas that the patients had throughout their lives. METHODS: Mini
      International Neuropsychiatric Interview, Polish version 5.0.0., Panic and
      Agoraphobia Scale, The Body Sensations Interpretation Questionnaire, Beck's
      Depression Inventory, Family Functioning Questionnaire (KOR), Antonovsky's Sense
      of Coherence Scale (SOC-29), Bond's Defence Style Questionnaire (DSQ-40) and Life
      Inventory were used. RESULTS: The proportion of women in the group of 97 severe
      asthmatics was 75%, which is in compliance with literature. This fact is probably
      due to specific trauma of suffering and/or death of an emotionally close person,
      which occurred in 80% of the study group. This trauma may have direct impact on
      the intensity of anxious and depressive symptoms, catastrophic interpretation of
      bodily sensations, coherence, a more frequent use of immature defence style and
      impaired family functioning. CONCLUSION: It is highly possible, that strictly
      psychological and psychiatric problems affect the severity of asthma more, than
      it was realised before.

PMID- 17444290
TI  - [Links between panic disorder, depression, defence mechanisms, coherence and
      family functioning in patients suffering from severe asthma].
AB  - BACKGROUND: Severe asthma, a dangerous, life-threatening lung disease is often
      comorbid with psychiatric problems. They in turn, could be a cause of bad asthma
      treatment outcome. AIM: The purpose of the study was to assess the prevalence of
      panic disorder and depression among patients with severe asthma. Defence style,
      sense of coherence and family functioning of patients were analysed in a link
      with psychiatric symptoms. METHODS: The authors examined 97 patients suffering
      from severe asthma. Mini International Neuropsychiatric Interview, Polish version
      5.0.0., Panic and Agoraphobia Scale, Beck's Depression Inventory, Family
      Functioning Questionnaire (KOR), Sense of Coherence Scale (SOC-29), Defence Style
      Questionnaire (DSQ-40) and Life Inventory were used. RESULTS: The study revealed
      that 70 % of the group with severe asthma suffered also from panic disorder and
      35% from depression (6% with severe depression). Depression was linked with
      severe panic symptoms and poor asthma treatment outcome. The more severe the
      course of panic disorder, the more severe depression, the more frequent use of an
      immature defence style, lower sense of coherence and impaired family functioning.
      CONCLUSION. It is highly possible, that psychiatric problems affect the severity
      of asthma.

PMID- 17444291
TI  - [Point prevalence of depression in the Krakow population of 10 year old children
      in 1984 and 2001].
AB  - Results of scarce epidemiological studies on depression in children are diverse
      and dependent of survey methodology as well as on the theoretical approach of the
      research. Those studies where the methods are comparable show that depression
      prevalence depends on the macrosocial situation and the adolescence stage. AIM:
      The study aimed to assess changes in depression prevalence in early-adolescents
      between 1984 and 2001. A presumption was made that the social situation in Poland
      had changed in the last 17 years. METHOD: In 2001 a representative sample of
      school attending 10 y.o. children was screened with KID AO "B I". The results
      were compared with those of a similar survey, using the same method, carried out
      in 1984. RESULTS: Point prevalence index in 2001 appeared to be lower than in the
      survey in 1984 (27.7% versus 38.2%). This resulted exclusively from a significant
      decrease in depression among boys (31.0% versus 46.6%) and girls (23.9% versus
      30.0%). CONCLUSION: The obtained data allows for an interpretation of the
      findings as a result of macrosocial changes. Other hypotheses e.g. the influence
      of the adolescence timing and course require a longitudinal prospective study.

PMID- 17444292
TI  - [Psychopathological syndromes and the problem of youth sexual orientation].
AB  - AIM: The objective of the paper is to present of ideas on relationships between
      sexual orientation and sanity of individuals. METHOD: The authors present a
      review of scientific news published by researchers, enhanced with case studies
      and formation of crucial factors leading to the evolution of psychiatric
      perturbations of the described cases. RESULTS: Analysis of the papers and self
      made research lead to the conclusion, that the most important risk factor for
      psychopathologic syndrome evolution in homosexuals and bisexuals is their social
      stigmatisation.

PMID- 17444293
TI  - [Vagus nerve stimulation in severe, treatment-resistent depression].
AB  - Since a few years, attempts are taken at the application of vagus nerve
      stimulation in the treatment of severe depression. It appears that the vagus
      nerve exerts a direct influence on areas of the brain associated with the
      regulation of mood and increases the level of biogenic amines. What is more,
      studies have confirmed an increased activity of fronto-orbital and prefrontal
      cortex, hypothalamus, cingulum and an increased concentration of serotonin and
      noradrenalin in the CNS and in the cerebro-spinal fluid. Preliminary clinical
      trials have confirmed the efficacy, good tolerance and safety of this treatment
      modality, although some objections have been raised whether these promising
      results were not partly due to the placebo effect. Therefore new, multicenter
      clinical studies have been designed, enabling an unbiased evaluation of
      usefulness of this method in the treatment of depression.

PMID- 17444294
TI  - [Acute delusional disorder with dissociative symptoms--case report].
AB  - Delusions are amongst the main symptoms of schizophrenia. Delusional states may
      be caused by stress, somatic illness, or may be idiopathic, such as the
      persistent delusional disorder. Determination of a cause is usually difficult,
      but it is really important for the treatment. A case report of acute delusional
      disorder complicated by dissociative symptoms, suggesting an organic cause of the
      disorder is presented. Delirium caused by neuroleptic intoxication was an
      additional complication. Detailed informations gathered from relatives and
      psychological examinations made it possible to determine personality disorder as
      a ground, and stress as a precipitating factor of acute delusional disorder.
      Hospitalisation and psychological support helped in getting rid of the psychotic
      symptoms.

PMID- 17444295
TI  - [Personality and behavioural disturbances, with delusional-hallucinatory and
      delirium episodes in the course of hyponatremia due to paraneoplastic
      inappropriate vasopressin secretion (SIADH)].
AB  - AIM: To broaden the knowledge about somatic mechanisms of psychic disturbances.
      METHOD: Presentation of a 54 year old male with psychic disturbances and
      hyponatremia. RESULTS: After six months with head ache, nausea, exhaustion,
      irritability, lacking drive, and appetite--acute psychic disturbances abruptly
      arose. These recurrent episodes with agitation, aggression, delusions,
      hallucinations, sometimes--disorientation and memory loss; appearing
      simultaneously with hyponatremia (Na in blood 104-118 mEq/L); were classified as
      organic delusional disturbances, and (in case of disorientation and memory loss)
      as delirium (F06.2, F05 - in ICD-10). The symptoms were manifested for 6 months
      and were classified as personality disturbances due to brain dysfunction (F07.8
      in ICD 10). The acute psychic disturbances interrupted the hospitalization in the
      medical ward, twice and caused three psychiatric hospitalizations; until the
      diagnosis of hyponatremia in the course of inappropriate vasopressin secretion
      (SIADH), due to small cell carcinoma of the left lung was established.
      CONCLUSION: The SIADH syndrome with hyponatremia, and polymorphic psychic
      disturbances had preceded the clinical and radiological manifestations of the
      hidden development of left lung small cell carcinoma for a long time. The
      legitimated involuntary admission to a psychotic ward in a general hospital with
      easy access to specialized laboratory tests and consultations facilitated
      establishing the diagnosis. The restriction of water administration with oral
      salt supplementation stabilized the psychic state and enabled treatment in the
      Institute of Oncology. The case illustrates the complicated somatic mechanisms of
      psychic disturbances and the necessity of multi-specialist cooperation in the
      border area between psychiatry and other medical disciplines.

PMID- 17444296
TI  - [The occurrence of psychotic disorders in epilepsy--a problem which is not fully
      known. Case history].
AB  - Connections between mental disorders and epilepsy have been perceived for a long
      period of time. Despite numerous investigations into this problem, it still is
      not fully understood in regard to the fact that in epilepsy the psychoses are
      situated at the intersection of neurology and psychiatry and the same phenomena,
      if presenting the psychotic syndrome, are often described in different terms. The
      most serious diagnostic as well as therapeutic problems are psychotic disorders
      which coexist with epileptic seizures. The goal of this paper was to present the
      case history of a patient, who was diagnosed with a psychotic disorder caused by
      partial complex seizures. The patient presented was hospitalized many times and
      several different neuroleptic treatments were used unsuccessfully. During the
      course of the illness many severe episodes of psycho-motor agitation connected
      with auto-aggressive acts were observed. It was not until an EEG - Holter test
      was performed and antiepileptic drugs were added to the treatment which aided in
      making the correct diagnosis. This enabled the patient to return to his highest
      level of functioning since the onset of the illness.

PMID- 17444297
TI  - [Pharmacological standards in schizophrenia treatment].

PMID- 17444298
TI  - Pay-for-performance: Medicare's new reimbursement twist.

PMID- 17444299
TI  - Medicare and Medicaid fraud and abuse--initiatives on the horizon.

PMID- 17444300
TI  - Health care reform and the Iowa General Assembly.

PMID- 17444301
TI  - Certificate of merit: common sense legislation for Iowa.

PMID- 17444302
TI  - The maturation of academic intensive care medicine in Australia and New Zealand:
      time to capitalise on progress.

PMID- 17444303
TI  - Epidural vs. multimodal analgesia for colorectal laparotomy.

PMID- 17444304
TI  - Acid-base and bio-energetics during balanced versus unbalanced normovolaemic
      haemodilution.
AB  - Fluids balanced to avoid acid-base disturbances may be preferable to saline,
      which causes metabolic acidosis in high volume. We evaluated acid-base and bio
      energetic effects of haemodilution with a crystalloid balanced on physical
      chemical principles, versus crystalloids causing metabolic acidosis or metabolic
      alkalosis. Anaesthetised, mechanically ventilated Sprague-Dawley rats (n=32,
      allocated to four groups) underwent six exchanges of 9 ml crystalloid for 3 ml
      blood. Exchange was with one of three crystalloids with strong ion difference
      (SID) values of 0, 24 (balanced) and 40 mEq/l. Controls did not undergo
      haemodilution. Mean haemoglobin concentration fell to approximately 50 g/l after
      haemodilution. With SID 24 mEq/l fluid, metabolic acid-base remained unchanged.
      Dilution with SID 0 mEq/l and 40 mEq/l fluids caused a progressive metabolic
      acidosis and alkalosis respectively. Standard base excess (SBE) and haemoglobin
      concentration were directly correlated in the SID 0 mEq/l group (R2 = 0.61),
      indirectly correlated in the SBE 40 mEq/l group (R2 = 0.48) and showed no
      correlation in the SID 24 mEq/l group (R2 = 0.003). There were no significant
      differences between final ileal values of CO2 gap, nucleotides concentration,
      energy charge, or luminal lactate concentration. SID 40 mEq/l crystalloid
      dilution caused a significant rise in subcutaneous lactate. In this group mean
      kidney ATP concentration was significantly less than controls and renal energy
      charge significantly lower than SID 0 mEq/l and control groups. We conclude that
      a crystalloid SID of 24 mEq/l provides balanced haemodilution. Bio-energetic
      perturbations with higher SID haemodilution may be more severe and need further
      investigation.

PMID- 17444305
TI  - The cardiovascular effects of adrenaline, dobutamine and milrinone in rabbits
      using pressure-volume loops and guinea pig isolated atrial tissue.
AB  - This study evaluated the effects of milrinone, adrenaline and dobutamine with
      pressure-volume loops and isolated atrial tissue. Agonist dose-response curves to
      incremental drug infusions were acquired in 11 anesthetised rabbits using
      pressure-volume loops and preload recruitable stroke work indicated
      contractility. Agonist concentration-response curves were completed in eight
      guinea pig isolated atria, for effects on atrial rate and force. Adrenaline and
      dobutamine increased contractility (P = 0.006 and 0.044), whereas milrinone did
      not (P = 0.895). Only adrenaline increased myocardial stiffness (P < 0.001).
      Milrinone decreased vascular resistance (P < 0.001) and elicited the greatest
      fall in mean arterial pressure (P < 0.001) and increased ejection fraction (P <
      0.001). Adrenaline decreased heart rate (P < 0.001), whereas dobutamine and
      milrinone increased it (P = 0.006 and 0.011). Milrinone increased the force of
      left atrial contraction, but its inotropic effect was weak and significantly less
      than with dobutamine and adrenaline (P < 0.001). Adrenaline acted as an
      inoconstrictor, dobutamine an inodilator and milrinone predominantly a
      vasodilator

PMID- 17444306
TI  - Use of elastin fibres detected in non-directed low volume bronchial lavage in
      ventilated ICU patients.
AB  - Elastin fibres in sputum have been described as a more sensitive marker of
      pulmonary necrosis than plain chest X-rays. This study aimed to determine the
      prevalence of elastin fibres using non-directed non-protected mini
      bronchoalveolar lavage (BM-BAL) in mechanically ventilated patients in the
      intensive care unit. Patients admitted to the general intensive care unit of a
      tertiary referral hospital requiring more than 48 hours of mechanical ventilation
      had surveillance BM-BAL performed on admission and were then examined weekly
      using potassium hydroxide wet preparations for the presence of elastin fibres.
      All positive and a random selection of 16 negative preparations from patients
      with acute respiratory distress syndrome or pneumonia were fixed and examined
      using Weigert's staining method for elastin. Of 412 patients enrolled, 130 (32%)
      had pneumonia on admission, 50 (12%) developed 58 episodes of ventilator
      associated pneumonia and acute respiratory distress syndrome was diagnosed in 86
      patients (21%). No chest X-ray showed cavitating infiltrates. Of 985 specimens
      examined, only seven had elastin fibres. Elastin fibres are uncommonly found
      using BM-BAL in general screening, acute respiratory distress syndrome or
      pneumonia in the intensive care unit, the incidence too low to be a useful
      indicator of pulmonary necrosis.

PMID- 17444307
TI  - A comparison of the degree of residual mitral regurgitation by intraoperative
      transoesophageal and follow-up transthoracic echocardiography following mitral
      valvuloplasty.
AB  - Patients who undergo mitral valve repair for mitral regurgitation and have mild
      residual mitral regurgitation may have an increased risk of re-operation in
      future years. Intraoperative transoesophageal echocardiography has now become a
      standard of practice for mitral valve repair surgery. We identified 106 patients
      who underwent attempted mitral valve repair over a three-year period in our
      institution. We retrospectively reviewed the grade of residual mitral
      regurgitation assigned following successful mitral valve repair ('mild' or less
      residual regurgitation) by intraoperative transoesophageal echocardiography and
      compared it to the observed grade of mitral regurgitation seen at follow-up
      transthoracic echocardiography. No patient had unexpected moderate or severe
      mitral regurgitation postoperatively, suggesting that intraoperative
      transoesophageal echocardiography performed in a medium-sized department is a
      sensitive tool for the early detection of failed mitral repair. Mild residual
      mitral regurgitation on intraoperative transoesophageal echocardiography was not
      reliably associated with mild mitral regurgitation on follow-up transthoracic
      echocardiography. In fact, 61% of patients with mild mitral regurgitation
      identified by intraoperative transoesophageal echocardiography had reduced mitral
      regurgitation at follow-up transthoracic echocardiography (to nil/trace residual
      mitral regurgitation). This observation, in conjunction with the limitations of
      the data supporting the goal of 'echo perfect' repair; suggests that a second
      attempt at repair should not be made based on the intraoperative transoesophageal
      echocardiography finding of mild residual mitral regurgitation alone.

PMID- 17444308
TI  - The use of ketamine as rescue analgesia in the recovery room following morphine
      administration--a double-blind randomised controlled trial in postoperative
      patients.
AB  - In some patients, control of postoperative pain can be difficult with morphine
      alone. This double-blind randomised controlled trial was designed to evaluate
      whether a small bolus dose of ketamine could improve pain scores in those
      patients who had inadequate relief of their postoperative pain after two standard
      doses of morphine. Forty-one patients with uncontrolled postoperative pain were
      randomly assigned to receive either morphine (M) alone, or morphine plus 0.25
      mg/kg ketamine (K) in the recovery room. No other analgesics were to be given.
      The study had adequate power to detect a 25% difference in pain scores. There was
      no statistically significant difference in verbal rating scale pain scores
      between the two groups either in the recovery room (K = 5.16, M = 6.28, P =
      0.065), or at a later time on the ward. There was no apparent difference between
      groups in sedation, morphine consumption, postoperative nausea and vomiting,
      quality of recovery or need for rescue analgesia. We could not demonstrate an
      effective role for ketamine in the management of problematic postoperative pain
      at the dose studied.

PMID- 17444309
TI  - The impact of bispectral index monitoring on sedation administration in
      mechanically ventilated patients.
AB  - The aim of this prospective randomised controlled trial was to assess the
      effectiveness of the Bispectral Index (BIS) monitor in supporting clinical
      sedation management decisions in mechanically ventilated intensive care unit
      patients. Fifty adult mechanically ventilated surgical and general intensive care
      unit patients receiving sedative infusions of morphine and midazolam were
      randomly allocated to receive BIS monitoring (n=25) or standard sedation
      management (n=25). In the BIS group, sedation was titrated to maintain a BIS
      value of greater than 70. In the standard management group, sedative needs were
      titrated based on subjective assessment and clinical signs. There was no
      statistically significant difference in the amount of sedation administered
      (morphine P = 0.67 and midazolam P = 0.85). However, there was a statistically
      significant difference in sedation administration over time. Patients in the BIS
      group received increasing amounts of sedation over time whilst those in the
      control group received decreasing amounts of sedation over time. The same inverse
      relationship existed for both sedative agents (morphine P = 0.005, midazolam P =
      0.03). Duration of mechanical ventilation was comparable in the two groups. We
      conclude that the use of BIS monitoring did not reduce the amount of sedation
      used, the length of mechanical ventilation time or the length of ICU stay.

PMID- 17444310
TI  - Variations in cerebral haemodynamics during irrigation phase in neuroendoscopic
      procedures.
AB  - Not many centres measure intracranial pressure during an endoscopic procedure.
      However, if the irrigation fluid during endoscopy is not simultaneously drained,
      then some rise in intracranial pressure can be anticipated. This study was
      carried out to measure and monitor changes in intracranial pressure during the
      irrigation phase in a neuroendoscopic procedure using a Codman catheter placed in
      the parenchyma. Intracranial pressure was monitored in 13 patients undergoing
      surgical neuroendoscopic procedures under a standardised anaesthetic technique.
      Heart rate, mean arterial pressure, intracranial pressure and cerebral perfusion
      pressure were recorded at baseline and during the irrigation phase of the
      procedure. The heart rate during irrigation was comparable to baseline values,
      but the mean arterial pressure at the time of irrigation increased an average of
      7 mmHg (P = 0.02). At the same time there was an average 34 mmHg increase in
      intracranial pressure (P < 0.001), producing an average 26 mmHg decrease in the
      cerebral perfusion pressure (P < 0.001) during irrigation. There was an average
      of four episodes of raised intracranial pressure (>25 mmHg) during the irrigation
      phase per patient. We suggest that the intracranial pressure be routinely
      monitored during neuroendoscopic procedures. Only then can the potential adverse
      effect of irrigation on intracranial pressure and cerebral perfusion pressure be
      assessed.

PMID- 17444311
TI  - Update in computer-driven weaning from mechanical ventilation.
AB  - Weaning from mechanical ventilation is a complex process requiring assessment and
      interpretation of both objective and subjective clinical parameters. For many
      years, automated computerised systems for various medical processes, including
      respiratory management, have been proposed to optimise decision-making and reduce
      variation amongst clinicians. SmartCare/PS, available since 2003 as a software
      application for the EvitaXL ventilator (Drager Medical AG & Co. KG, Lubeck,
      Germany), is one of the first such ventilator systems to be made commercially
      available. SmartCare/PS can be described as a knowledge-based weaning system,
      which adjusts pressure support based on measurement of the patient's respiratory
      status, specifically the spontaneous respiratory rate, tidal volume and end-tidal
      carbon dioxide with the aim of optimising the weaning process. The primary
      proposed advantage of this system is an ability to provide management of
      ventilatory weaning through continuous physiological monitoring and real-time
      interventions. The relatively small number of available clinical studies indicate
      the system is able to deliver appropriate ventilation during pressure support
      weaning from both short-term and prolonged ventilation. Of potential clinical
      note, a recent study suggested that use of SmartCare/PS might be associated with
      useful reductions in the duration of weaning compared to existing clinical
      practice using weaning protocols. One recently published randomised trial
      supports this conclusion. However, given the known large variation in
      international critical care ventilatory practices further randomised trials are
      desirable.

PMID- 17444312
TI  - The proseal laryngeal mask airway in prone patients: a retrospective audit of 245
      patients.
AB  - The use of the classic laryngeal mask airway (classic LMA) in the prone position
      is controversial, but the ProSeal laryngeal mask airway (ProSeal LMA) may be more
      suitable as it forms a better seal and provides access to the stomach. In the
      following retrospective audit, we describe our experience with the insertion of
      and maintenance of anaesthesia with, the ProSeal LMA in 245 healthy adults in the
      prone position by experienced users. The technique involved (1) the patient
      adopting the prone position with the head to the side and the table tilted
      laterally; (2) pre-oxygenation to end-tidal oxygen >90%; (3) induction of
      anaesthesia with midazolam/alfentanil/propofol; (4) facemask ventilation (5) a
      single attempt at digital insertion and if unsuccessful a single attempt at
      laryngoscope-guided, gum elastic bougie-guided insertion; (6) gastric tube
      insertion; (7) maintenance of anaesthesia with sevoflurane/O/N2O; (8) volume
      controlled ventilation at 8-12 ml/kg; (9) emergence from anaesthesia in the
      supine position; and (10) removal ofthe ProSeal LMA when awake. Facemask
      ventilation was always successful. ProSealLMA insertion was successful in all
      patients: 237 with digital insertion and eight with bougie-guided insertion.
      Ventilation was successful in all patients. Gastric tube insertion was successful
      in all patients. Correctable partial airway obstruction occurred in three
      patients, but there was no hypoxia, hypercapnoea, displacement, regurgitation,
      gastric insufflation or airway reflex activation. Our findings suggest that the
      insertion of and maintenance of anaesthesia with the ProSeal LMA is feasible in
      the prone position by experienced users.

PMID- 17444313
TI  - Performance comparison of two anaesthetic facemasks.
AB  - When considering anaesthetic masks, the quality of the mask-face seal is a key
      determinant of performance. This randomised crossover trial utilises expired
      oxygen concentration to compare the efficacy of two routinely used facemasks.
      Thirty subjects were randomised to breathe 100% oxygen via either a traditional
      reusable black rubber mask or the disposable Intersurgical Scented mask for three
      minutes. This was then repeated using the other mask. To compare the impact of
      mask design on the quality of the mask-face seal, it was necessary to minimise
      measures taken by the anaesthetist to correct for a poor seal. To achieve this,
      the anaesthetist was requested to hold the mask in a manner consistent with an
      airtight seal, but they were blinded to capnography and reservoir bag movement.
      Expired oxygen concentration was recorded at 15-second intervals. From the oxygen
      wash-in curves, the Intersurgical mask consistently outperformed the black rubber
      mask. At three minutes the Intersurgical mask performed better than the black
      rubber mask, with mean end-tidal oxygen concentrations of 86.9% vs. 81%
      respectively; P=0.008. These findings indicate that the soft cuff design of the
      intersurgical mask provided a better seal than the black rubber facemask.

PMID- 17444314
TI  - Changing from epidural to multimodal analgesia for colorectal laparotomy: an
      audit.
AB  - In April 2002 our practice ceased routine use of epidural analgesia for
      colorectal laparotomy in favour of a six-drug multimodal regimen comprising
      ketamine, clonidine, morphine, tramadol, paracetamol and a non-steroidal anti
      inflammatory drug. The records of 54 patients who received this multimodal
      analgesia regimen (MM) after April 2002 were compared to the 59 patients who had
      previously received epidural analgesia (EPI). Patients had the same surgeon and
      anaesthetist. Daily pain score (verbal rated 0-10) at rest (mean) over the first
      three postoperative days was satisfactorily low with both MM (1.2 +/- 1.2) and
      EPI (0.4 +/- 0.4). Over this period there was little difference between the
      maximum pain score at rest (MM 2.3 +/- 1.9 vs. EPI 2.2 +/- 1.7, P = 0.58). Major
      complications and side-effects occurred solely in EPI patients: epidural abscess
      (1), respiratory depression (2), pneumonia (3), venous thromboembolism (3),
      delirium (7), high block (7) and motor block (3). Hypotension requiring
      intervention was 4.8 times more frequent in the EPI group (95% CI 2.1-11).
      Antiemetic use was similar between groups; on average 13 patients in the MM
      groups (24%) and 15 patients in the EPI groups (26%) received antiemetics each
      day. MM patients had shorter anaesthetic preparation time (20 +/- 8 min vs. 32 +/
      8 min, P < 0.001), shorter high-dependency unit stay (0.4 +/- 1.2 days vs. 4.5
      +/- 0.9 days, P < 0.001), and shorter hospital stay (10 +/- 4 days vs. 13 +/- 8
      days, P = 0.003). In our practice, changing from epidural to multimodal analgesia
      produced comparable pain relief with reduction in anaesthesia preparation time,
      high-dependency unit stay and hospital stay and the requirement for staff
      interventions. There was also a reduction in the incidence of major complications
      and side-effects.

PMID- 17444315
TI  - Is there evidence to support the use of lateral positioning in intensive care? A
      systematic review.
AB  - A systematic review of randomised clinical trials was conducted to investigate
      the efficacy and safety of use of the lateral position in the management of
      ventilated intensive care patients. One review article and 11 empiric studies,
      which were mostly of low methodological quality, met the eligibility criteria.
      Large individual variations in PaO2 response to lateral positioning were
      demonstrated. Greatest improvement in PaO2 occurred in patients with
      unilateralpulmonary infiltrates positioned with the bad lung up versus bad lung
      down (average difference = 33.6 mmHg (range 0-58), effect size 1.13 (95% CI:
      0.44, 1.19, P = 0.001)) or supine (average difference=27 mmHg (range 5-42),
      effect size 0.58 (95% CI: 0.11, 1.06, P = 0.017)). This effect appeared to be
      most prominent in patients with widespread, unilateral infiltrates. Lung
      compliance was not affected by lateral positioning. Haemodynamic compromise was
      evident with lateral positioning of greater than 60 degrees to the right side in
      patients requiring vasopressors and/or with right ventricular dysfunction; or
      with lateral positioning in postoperative coronary artery bypass graft patients.
      No studies were found that had investigated the effect of routine applications of
      the lateral positioning to improve, prevent or treat pneumonia, decrease
      mortality or influence other long-term outcomes. The results of this review
      demonstrate the limited evidence available to support the use of lateral
      positioning in the intensive care environment. More data reporting the long-term
      effects of lateral position on long-term outcomes would aid clinical decision
      making and may improve the application of patient positioning in critical care
      environments.

PMID- 17444316
TI  - The use of statins in intensive care unit patients with sepsis.
AB  - The incidence of sepsis is increasing and remains the leading cause of death in
      critically ill patients. The statin group of drugs appear to have important anti
      inflammatory effects and may have a role in the treatment of sepsis. However,
      current prescribing guidelines recommend that statin therapy is discontinued in
      critically ill patients. We found no evidence to support commencing statin
      therapy in patients with sepsis on an intensive care unit and low levels of
      evidence to support continuing established therapy in this patient population.

PMID- 17444317
TI  - ICU staffing: identification and survey of staff involved in providing technical
      support services to Australian and New Zealand intensive care units.
AB  - We conducted a survey of all (200) Australian and New Zealand intensive care
      units to determine the presence and nature of staff employed in a technical
      support role. Specifically, we attempted to identify staff who are formally
      employed in a role where they are directly responsible for the equipment used in
      intensive care. Of 130 returned surveys, 80 units (62%) reported not having any
      personnel in this role. In these units technical tasks were most commonly
      performed by registered nurses (79%) but were also performed by a variety of
      other personnel. Fifty units (38%), consisting of approximately 105 individuals
      providing a total of 84.3 EFTs and most commonly in public (84%) or metropolitan
      (70%) hospitals or level 3 (64%) intensive care units, did have one or more staff
      acting in a formal technical support role. The most common groups filling the
      technical support role were nurses (42%), technicians (24%), biomedical engineers
      (10%) and technologists (6%). The most common duties performed were equipment
      troubleshooting (92%), training (80%), equipment evaluation (80%), ordering
      supplies (77%), consumable evaluation (75%), equipment cleaning (73%), delivery
      of supplies (70%), handling product recalls (65%), equipment maintenance (65%)
      and sitting on hospital committees (52%). This is the first attempt to identify
      and understand the technical support role in Australian and New Zealand intensive
      care units. Numerous issues remain and future work will hopefully add to our
      findings, with the possibility of formal recognition of the role, training and/or
      accreditation and its extension into other hospital departments.

PMID- 17444318
TI  - Ultrasound guided dorsal penile nerve block in children.
AB  - We describe a technique for using a portable ultrasound scanner (38 mm broadband
      (10-5 MHz) linear array transducer (Sonosite Titan SonoSite, Inc. 21919 30th
      Drive SE Bothell, WA.)) to guide dorsal penile nerve block in children under
      general anaesthesia. Real-time scanning is used to guide bilateral injections
      into the sub-pubic space, deep to Scarpa's fascia either side of the midline
      fundiform ligament. Scanning can confirm that the local anaesthetic has spread to
      contact the deep fascia on each side. A subcutaneous wheal of local anaesthetic
      along the penoscrotal junction completes the block.

PMID- 17444319
TI  - Pneumothorax in association with spontaneous ventilation general anaesthesia--an
      unusual cause of hypoxaemia.
AB  - A 43-year-old ASA PS II male patient developed a pneumothorax while breathing
      pontaneously through a supraglottic airway device during a general anaesthetic.
      Unexplained hypoxaemia occurred after an episode of coughing. Clinical
      examination appeared to be normal apart from the persistent oxygen desaturation.
      A pneumothorax was diagnosed in the post anaesthesia care unit by chest X-ray.
      The pneumothorax responded to conventional management and the patient made an
      uneventful recovery. We recommend a high index of suspicion in any patient who
      coughs and later has unexplained hypoxaemia during general anaesthesia, even if a
      supraglottic airway device has been inserted.

PMID- 17444320
TI  - Right upper lobe collapse secondary to an anomalous bronchus after endotracheal
      intubation for routine surgery.
AB  - Perioperative hypoxaemia is a common but serious problem with well recognised
      causes. However, an anomalous bronchus causing lobar collapse as a cause is
      seldom mentioned. A healthy young male patient was anaesthetised for a knee
      operation. He required re-intubation immediately postoperatively for hypoxia. He
      was found to have right upper lobe collapse. Fibreoptic examination of the
      trachea demonstrated an anomalous bronchus as the cause. Intra-operatively, the
      endotracheal tube had been inserted too deeply and the bronchial orifice had been
      obstructed by the tip. It took several hours for the lung to re-expand. Greater
      awareness of this potential complication is needed.

PMID- 17444321
TI  - Late onset nephrogenic diabetes insipidus following cessation of lithium therapy.
AB  - Lithium-induced diabetes insipidus occurs in up to one third of patients on long
      term therapy. It usually manifests during the treatment course, often with
      preceding signs or symptoms. We wish to highlight a case in which diabetes
      insipidus developed many days after cessation of long-term lithium therapy. We
      seek to explain this delayed onset by a discussion of the molecular and genetic
      changes underlying the pathogenesis of lithium-induced nephrogenic diabetes
      insipidus.

PMID- 17444322
TI  - Anaesthesia for robotic-assisted radical prostatectomy: considerations for
      laparoscopy in the Trendelenburg position.
AB  - Two cases of anaesthetic complications after robotic-assisted laparoscopic
      radical prostatectomy using the da Vinci Remote-Controlled Surgical System are
      presented. Case 1 describes a patient with post-extubation respiratory distress
      requiring re-intubation and subsequent ventilation in an intensive care unit.
      This was attributed to laryngeal oedema, which was most likely due to the
      reduction in venous outflow from the head caused by the pneumoperitoneum and
      prolonged, extreme Trendelenburg position. Case 2 describes a patient with mild
      brachial plexus neurapraxia, which was most likely due to compression by shoulder
      braces (to prevent cephalad sliding) during the exaggerated head-down tilt. For
      this procedure, the authors recommend limiting the duration and extent of head
      down tilt as much as possible, avoiding excessive intravenous fluids and careful
      positioning of the patient with avoidance of shoulder braces whenever possible.

PMID- 17444323
TI  - Aniline-induced methaemoglobinaemia in a glucose-6-phosphate dehydrogenase enzyme
      deficient patient.
AB  - A case of methaemoglobinaemia following ingestion of an aniline-containing
      material is described. The detrimental effect of methylene blue, the classical
      antidote of methaemoglobinaemia, in a patient with glucose-6-phosphate
      dehydrogenase deficiency is highlighted.

PMID- 17444324
TI  - Treatment of multilevel degenerative disc disease with intradiscal electrothermal
      therapy.
AB  - Intradiscal electrothermal therapy is a frequently performed procedure for the
      pain of internal disc disruption. It is typically performed on one to two discs;
      the discal treatment is followed by a long period of rest and rehabilitation. In
      patients with multilevel disc disease, intradiscal electrothermal therapy is
      either not contemplated or only one to two discs are treated at a time. This
      approach therefore either denies these patients the potential benefits of
      intradiscal electrothermal therapy or significantly prolongs the period of pain
      and disability. A 25-year-old female patient presented with internal disc
      disruption at four lumbar disc levels, diagnosed by provocative discography and
      post discography CT scan. All these discs were treated simultaneously by
      intradiscal electrothermal therapy. The patient tolerated the procedure well and
      responded favourably with significant and prolonged decrease in her symptoms. She
      reported sustained reduction in her pain and showed no clinical evidence of early
      neurological or infectious complications during 18 months of follow-up. This
      report indicates that intradiscal electrothermal therapy can be performed at
      multiple levels at a single sitting, compared to intradiscal electrothermal
      therapy performed at one to two discs at a time, this approach may obviate the
      need for surgery and may reduce the duration of pain and disability incurred.
      However, the influence of multilevel intradiscal electrothermal therapy on long
      term complications or outcome is not known.

PMID- 17444325
TI  - Acute pulmonary embolectomy three days following a coronary artery bypass graft
      procedure.
AB  - Pulmonary embolism is very rarely reported early after cardiac surgery, most
      probably due to full heparinisation during cardiopulmonary bypass. We report a 66
      year-old man without thromboembolic history who presented three days after a
      coronary artery bypass grafting procedure with acute dyspnoea and haemodynamic
      instability. A CT scan confirmed paracentral bilateral pulmonary embolism
      requiring an urgent and successful embolectomy. Review of the literature confirms
      that pulmonary embolism may occur in up to 3% of post-cardiopulmonary bypass
      patients. The possibility of pulmonary embolism must be taken into consideration
      in post-cardiopulmonary bypass patients with acute onset of chest pain and
      respiratory insufficiency.

PMID- 17444327
TI  - A simple technique for oesophageal stethoscopy.

PMID- 17444326
TI  - Approach to labour analgesia in a pregnant woman with spina bifida is one of
      individuality.

PMID- 17444328
TI  - Epidural etanercept for lumbar radiculopathy.

PMID- 17444329
TI  - Anaesthetic considerations during ERCP.

PMID- 17444330
TI  - TIVA: have you performed a leak test?

PMID- 17444331
TI  - Pressure sore on malar prominences by horseshoe headrest in prone position.

PMID- 17444332
TI  - Anaesthesia and Alstrom's syndrome.

PMID- 17444333
TI  - Peripheral nerve injury caused by misuse of elastic stockings.

PMID- 17444334
TI  - Tension pneumoperitoneum, pneumomediastinum, subcutaneous emphysema and
      cardiorespiratory collapse following gastroscopy.

PMID- 17444335
TI  - "Torted" reservoir bag: an unusual cause for 'cannot ventilate' situation.

PMID- 17444336
TI  - ProSeal Laryngeal Mask Airway in a myasthenia gravis patient for thymectomy.

PMID- 17444337
TI  - Mediastinal tumor resection under the guidance of transoesophageal
      echocardiography.

PMID- 17444338
TI  - Stings and hopes: toxinomics and autonomic storm in the Indian red scorpion
      (Mesobuthus tamulus concanesis, Pocock).

PMID- 17444339
TI  - Utility of scorpion antivenin vs prazosin in the management of severe Mesobuthus
      tamulus (Indian red scorpion) envenoming at rural setting.
AB  - BACKGROUND: Scorpion antivenom (SAV) is specific antidote to scorpion venom..SAV
      did not prevent the cardiovascular morbidity and mortality (autonomic storm),
      hence its utility in the management for severe scorpion envenomingmay be limited.
      Since 1983 the advent of prazosin revolutionized the management of severe
      scorpion sting. Since 2002 SAV against Indian red scorpion (IRS) for the
      treatment of scorpion sting cases is available at primary health centers. We
      compared the effects of SAV Vs Prazosin (PRA) in the management of severe
      scorpion stung cases at rural setting in a non-randomised open label manner.
      METHODS: From January 2002 to December 2004, 53 patients accidentally stung by
      scorpion were admitted in hospital at Mahad. Of these 25 patients received
      intravenous SAV at primary health centers and were referred to Mahad for further
      management. 28 patients directly reported to Mahad were treated with oral
      prazosin (PRA). Time interval between sting and hospitalization, the total dose
      of SAV and PRA administered was noted. Clinical manifestations were noted in a
      standard protocol. Details of SAV patients were noted from referred letters or in
      case of a doubt, details were obtained by direct communication with the medical
      officer who first saw and examined the case. All 53 cases were evaluated
      clinically for improvement, deterioration or fatal outcome. RESULTS: SAV Vs PRA (
      25 Vs 28) cases reported to hospital within 11/2 -3 (1.4) Vs 1/2-4 (1.3) hours
      after stung. On arrival 21 (84%) Vs 26 (92%) had hypertension, 2 (8%) Vs 1 (3.5%)
      had hypotension, 2 (8%)Vs 1 (3.5%) had normal blood pressure. Heart rate 58-102
      (82) Vs 48-120 (80.2) respectively. 9 cases received 20 ml, 1 case 30 ml and
      remaining 15 cases were given 10 ML of SAV on arrival to PHC, while 28 cases
      received oral prazosin. 20 (80%) Vs 2 (7.5%) had acute pulmonary edema, 5 (20%)
      Vs 8 (30%) had persistent raised blood pressure. 4 (16%) Vs 0% died. Recovery
      time was 11-4 (2.26) Vs 1-2 (1.25) days respectively. CONCLUSION: We found that
      SAV is no more effective to alleviate or reverse the cardiovascular effects of
      scorpion venom actions in severe case as against prazosin prevents and cures the
      cardiovascular manifestations in a severe scorpion envenomation. Therefore role
      of SAV in severe scorpoin venomation needs to be relooked and prazosin needs to
      be a standard of care in such cases to overcome the autonomic storm.

PMID- 17444340
TI  - Captopril in the treatment of cardiovascular manifestations of indian red
      scorpion (Mesobuthus tamulus concanesis Pocock) envenomation.
AB  - OBJECTIVES: To study outcome of patients with scorpion envenomation treated with
      oral captopril in the ICU of a Tertiary Care, University Hospital in Mumbai.
      METHODS: Retrospective analysis of all patients with scorpion sting admitted to
      Medical Intensive Care Unit of a tertiary care university hospital in Mumbai
      between 1993 and 2003. RESULTS: Of 38 patients with cardiovascular
      manifestations, six had tachycardia alone and 8 had hypertension; these patients
      received oral captopril 12.5-25 mg thrice daily with no deaths. Pulmonary oedema
      with normal blood pressure and high central venous pressure (CVP) was seen in 10
      patients. Five patients had hypotension, low CVP but no pulmonary oedema; with
      fluid infusion, these patients had correction of low CVP and hypotension, but
      developed pulmonary oedema. Pulmonary oedema resolved in all 15 patients with
      captopril (6.25-25 mg thrice daily): one patient died of ventricular tachycardia.
      Nine patients had cardiogenic shock; 6 patients, whose blood pressure improved
      with dopamine received, captopril; 1 of these 6 died. The other three patients
      did not respond to maximum vasopressor therapy and could not be given captopril;
      all three died. Four of the 5 deaths occurred in patients weighing < 25 kg
      suggesting that severity of cardiovascvlar manifestations also depends on body
      weight of the victim. CONCLUSION: Afterload reduction with oral captopril is safe
      and effective in scorpion envenomation with cardiovascular manifestations.
      Results are similar to those with other vasodilators.

PMID- 17444341
TI  - Cardiovascular risk factors in tobacco-chewers: a controlled study.
AB  - BACKGROUND: Influence of habitual tobacco chewing on cardiovascular risk has not
      been well studied. To determine prevalence of major cardiovascular risk factors
      in subjects who habitually chew tobacco we performed a controlled study. METHODS:
      A population based case-control study was performed in Bikaner in North-western
      India where the prevalence of tobacco-chewing is high. Successive 200 subjects
      who agreed to participate in the evaluation and had a history of isolated tobacco
      chewing (range 10-60 years) were enrolled (Group III). The prevalence of major
      coronary risk factors- obesity, truncal obesity, hypertension, fasting
      hyperglycemia, and lipid levels were estimated using current guidelines.
      Electrocardiogram was also performed in all subjects. Chest radiography and
      treadmill stress test was done in subjects when indicated by symptoms. 200 age-
      and gender-matched controls who did not use tobacco in any form (Group I) and 200
      subjects who had history of smoking bidis or cigarettes for more than 10 years
      (range 10-55 years) (Group II) were also evaluated. RESULTS: The body-mass index
      and obesity were lowest in smoker group. Tobacco chewers had a significantly
      higher (p<0.001) systolic blood pressure (BP), diastolic BP, resting heart rate,
      total cholesterol, LDL cholesterol and triglycerides as compared to controls and
      was similar to smoker group. There was a significantly greater (p<0.01)
      prevalence of hypertension, hypercholesterolemia, hypertriglyceridemia,
      radiographic cardiomegaly and positive stress test in Group III as compared to
      controls. Prevalence of these risk factors was similar among Group II and Group
      III subjects. HDL cholesterol levels were the lowest in tobacco-chewing group
      (44.3+/-8.1 mg/dl) as compared to the Group I (48.4+/-7.8) and Group II (47.4+/
      7.5) (p<0.001). CONCLUSIONS: There is a significantly greater prevalence of
      multiple cardiovascular risk factors obesity, resting tachycardia, hypertension,
      high total and LDL cholesterol, and low HDL cholesterol, and electrocardiographic
      changes in tobacco users, chewing or smoking, as compared-to tobacco non-users.
      Chewing tobacco is associated with similar cardiovascular risk as smoking.

PMID- 17444342
TI  - Cardiovascular events in systemic lupus erythematosus and rheumatoid arthritis :
      emerging concepts, early diagnosis and management.
AB  - The incidence of cardiovascular disease is significantly increased in the two
      common autoimmune disorders Systemic Lupus Erythematous (SLE) and Rheumatoid
      Arthritis (RA). Cardiovascular mortality is a major cause of death in these
      patients. This has been linked to acceleration of the atherosclerotic process in
      these disorders. Traditional cardiovascular risk factors alone cannot fully
      explain the accelerated atherogenesis in these disorders. In addition to the
      systemic inflammation, additional mechanisms have been put forward that are more
      specific for the pathophysiology of these autoimmune chronic inflammatory
      disorders. Further, longitudinal studies are required to define optimal
      preventive strategies for cardiovascular comorbidity in SLE and RA.

PMID- 17444343
TI  - Recurrent submandibular gland swelling as the initial presentation of Sjogren's
      syndrome.

PMID- 17444344
TI  - Erythema marginatum.

PMID- 17444345
TI  - Management of venous thromboembolism.
AB  - INTRODUCTION: Venous Thromboembolism is an important healthcare problem the world
      over, resulting in significant morbidity, mortality and resource expenditure. The
      rationale for use of thromboprophylaxis is based on solid principles and
      scientific evidence. Indian perspective on this topic is lacking due to the non
      availability of published Indian data. This document reviews the available
      International and Indian data and discusses the relevance of recommendations for
      prevention and management of Venous Thromboembolism (VTE) in the Indian context.
      MATERIALS AND METHODS: Meetings of various specialists from different Indian
      hospitals in the field of Gastrointestinal Surgery, General and Vascular Surgery,
      Hematology, Intensive Care, Obstetrics and Gynecology, Oncology and Orthopedics
      were held in the months of August 2005 to January 2006. The guidelines published
      by American College of Chest Physicians (ACCP), the International Union of
      Angiology (IUA), and the Royal College of Obstetricians and Gynecologists (RCOG),
      were discussed during these meetings. The relevance of these guidelines and the
      practical implications of following these in a developing country like India were
      also discussed. Any published data from India was collected from data base
      searches and the results, along with personal experiences of the participating
      specialists were discussed. The experiences and impressions of the experts during
      these meetings have been included in this document. Data from recent sources
      (International Union of Angiology and the National Comprehensive Cancer Network
      (NCCN) Practice guidelines in Oncology on Venous thromboembolic disease) was
      subsequently also included in this document. RESULTS: The suggestions formulated
      in this document are practical, and would intend to serve as a useful practical
      reference. CONCLUSIONS: A number of unanswered questions remain in the field of
      thromboprophylaxis, and carefully designed research protocols may help answer
      some of these. Implementation of the suggestions outlined in the document remains
      to be studied in the Indian context.

PMID- 17444346
TI  - Organophosphate induced delayed neuropathy.
AB  - A 19 year young male who consumed organophosphorous compound and required
      assisted mechanical ventilation for two weeks, later on developed delayed
      neuropathy is described.

PMID- 17444347
TI  - Refractory hyperkalaemia due to trimethoprim, successfully treated with
      fludrocortisone.
AB  - We report a case of intractable hyperkalaemia in an elderly patient with myeloma,
      who received conventional dose of trimethoprim-sulfamethoxazole and hyperkalaemia
      resolved following therapy with fludrocortisone. We recommend monitoring of serum
      potassium in high-risk patients receiving conventional doses of trimethoprim
      sulfamethoxazole for 5 or more days.

PMID- 17444348
TI  - Primary duodenal lymphoma producing obstructive jaundice.
AB  - Primary lymphoma of the duodenum presenting with obstructive jaundice is a rare
      entity. We report a case of primary non-Hodgkin's lymphoma of the duodenum
      producing obstructive jaundice in a middle aged lady, where the concentric
      thickening of the duodenal wall also gave rise to symptomatic partial high small
      bowel obstruction in due course. Guided aspiration and flowcytometry established
      a diagnosis of diffuse large B-cell lymphoma.

PMID- 17444349
TI  - Secondary Sjogren's syndrome and scleroderma presenting as renal tubular
      acidosis.
AB  - We report a case of distal renal tubular acidosis in a twenty year old female
      patient of scleroderma and secondary Sjogren's syndrome. This patient presented
      with two episodes of flaccid quadriparesis which were associated with
      hypokalaemia and was later found to have an underlying scleroderma with secondary
      Sjogren's syndrome.

PMID- 17444350
TI  - Medical philately (medical theme on stamps). Virginia Apgar (1909-1974).

PMID- 17444351
TI  - Falling after CABG.

PMID- 17444352
TI  - A focus group study among type 2 diabetic subjects.

PMID- 17444353
TI  - Adult Onset Still's Disease.

PMID- 17444354
TI  - Communication: patient safety and the nursing work environment.

PMID- 17444355
TI  - The clinical nurse leader: new role in nursing.

PMID- 17444356
TI  - The power of positive nursing.

PMID- 17444357
TI  - Trait dissociation and commission errors in memory reports of emotional events.
AB  - In 2 studies we examined whether trait dissociation is related to spontaneous
      commission errors (reports of events that did not occur) in free recall of
      emotional events. We also explored whether the functional locus of the
      dissociation-commission link is related to repeated retrieval or shallow
      encoding. In Experiment 1 participants were exposed to a staged incident and were
      repeatedly asked to add more information to their written accounts of the event.
      Dissociation levels were related to commission errors, indicating that people who
      report many dissociative experiences tend to make more commission errors.
      However, it was not the case that the overall increase in commission errors over
      successive retrieval attempts was typical for high dissociative participants. In
      Experiment 2 participants saw a video fragment of a severe car accident. During
      the video, half the participants performed a dual task, and the other half did
      not. Participants performing the dual task made more commission errors than
      controls, but this effect was not more pronounced in those with high trait
      dissociation scores. These studies show that there is a link between dissociation
      and spontaneous commission errors in memory reports of emotional events, but the
      functional locus of this link remains unclear.

PMID- 17444358
TI  - Psychological reactance: examination across age, ethnicity, and gender.
AB  - Psychological reactance is a motivational state aroused when real or perceived
      personal freedoms are threatened, reduced, or eliminated. Although psychological
      reactance theory has existed for almost 40 years, there is still dissent over
      some of its most basic characteristics. Research on age and ethnicity is scant,
      and research on gender has not produced a clear pattern of results. We attempted
      to clarify the relationships of these variables to psychological reactance. A
      total of 3,499 undergraduates completed the Therapeutic Reactance Scale and a
      brief demographic questionnaire. We found a curvilinear relationship between age
      and reactance, with older and younger participants exhibiting higher reactance
      than the middle age group. African Americans, Asians, and Hispanics exhibited
      higher total, behavioral, and verbal reactance than Caucasians and Native
      Americans. Men produced higher total, behavioral, and verbal reactance scores
      than women. We discuss the implications of these findings and make suggestions
      for further research.

PMID- 17444359
TI  - Cognitive processes involved in blame and blame-like judgments and in forgiveness
      and forgiveness-like judgments.
AB  - Experiment 1 compared the cognitive processes involved in blame and forgiveness
      judgments under identical experimental conditions. Experiment 2 was a replication
      of Experiment 1 with 4 judgment scales: willingness to prosecute, willingness to
      avenge, resentment level, and willingness to make up. Participants were presented
      with 32 scenarios in which a doctor made a medical error. These situations
      contained 5 items: the degree of proximity with the doctor (e.g., a family doctor
      known since childhood), the degree of negligence, the severity of consequences,
      apologies or contrition, and cancellation of consequences. Functional cognitive
      analysis grouped judgments into 2 categories: blame-like judgments (blame,
      prosecution, and revenge) and forgiveness-like judgments (resentment,
      forgiveness, and reconciliation). Blame-like judgments were characterized by
      additive integration rules, with negligence followed by apologies as the 2 main
      cues. Forgiveness-like judgments were characterized by an interactive integration
      rule, with apologies followed by negligence as the 2 main cues.

PMID- 17444360
TI  - Aesthetic preferences for the unity ratio resist the influence of color
      illusions.
AB  - The addition of color produces an extension of previous research examining
      aesthetic preferences for proportional relationships. To date, most favored
      preferences have been for the unity (1:1) and golden section (1.618:1) ratios.
      Two experiments examined preferences in and assessed the accuracy of
      areajudgments for divided figures that varied in saturation contrast and were
      presumed to present a complementary color illusion. Regardless of colors,
      saturation contrast, direction of division, or area-to-area ratio, participants
      were accurate in locating the boundary between the two areas of the divided
      figure, and preferences for the unity ratio dominated as the most preferred
      ratio. There was no notable interest in the golden section ratio. Looking at the
      world through colored glasses seems not to interfere with a preference for
      symmetry, as produced by the unity ratio.

PMID- 17444361
TI  - Emotional arousal and memory: a test of the poststimulus processing hypothesis.
AB  - Emotional arousal is believed to enhance memory for details central to an episode
      but impair memory for peripheral details. However, new research suggests that
      arousal induced thematically (i.e., through involvement with an unfolding event)
      produces only memory enhancements. This article examines whether consciously
      controlled elaborative processing in the aftermath of an arousing experience is
      responsible. A dual task manipulation was used to prevent participants from
      ruminating over a video that depicted an abduction and attack. Several indices of
      recall showed greater memory for emotional event details than for details from a
      neutral control video, which remained the case when the opportunity for post
      stimulus elaboration was prevented. Thus, superior retention of the content of
      emotional experiences may arise from the way in which arousal is induced rather
      than through immediate postevent cognitions.

PMID- 17444362
TI  - Hypnotic history: a reply to critics.
AB  - This article responds to comments on Kirsch, Mazzoni, & Montgomery (2007).
      Contrary to the perceptions of some commentators, the target article was not
      aimed at supporting a particular view of hypnosis. Instead, it was a reminder of
      a long accepted axiom in hypnosis research: the effects of hypnotic suggestions
      cannot be attributed to hypnosis unless it is demonstrated that the same
      suggestion does not produce the effect outside of hypnosis.

PMID- 17444363
TI  - Hypnosis prevents the cardiovascular response to cold pressor test.
AB  - To highlight the effects of hypnotic focused analgesia (HFA), 20 healthy
      participants underwent a cold pressor test (CPT) in waking basal conditions (WBC)
      by keeping the right hand in icy water until tolerable (pain tolerance);
      subjective pain was quantified by visual scale immediately before extracting the
      hand from water. The test was then repeated while the participants were under
      hypnosis and underwent HFA suggestions. Cardiovascular parameters were
      continuously monitored. Pain tolerance was 121.5+/-96.1 sec in WBC and 411.0+/
      186.7 sec during HFA (p < 0.0001), and visual rating score 7.75+/-2.29 and 2.45+/
      2.98 (p < 0.0001), respectively. CPT-induced increase of total peripheral
      resistance was non significant during HFA and +21% (p < 0.01) in WBC. HFA
      therefore reduced both perception and the reflex cardiovascular consequences of
      pain as well. This indicates that hypnotic analgesia implies a decrease of
      sensitivity and/or a block of transmission of painful stimuli, with depression of
      the nervous reflex arc.

PMID- 17444364
TI  - What is a suggestion? The neuroscience of implicit processing heuristics in
      therapeutic hypnosis and psychotherapy.
AB  - Neuroscience and bioinformatics research on activity-dependent gene expression
      and brain plasticity in memory and learning are used to reconceptualize a
      fundamental question of therapeutic hypnosis, "What is a suggestion?" John
      Kihlstrom's cognitive-behavioral perspective of implicit (unconscious) and
      explicit (conscious) memory and Eric Kandel's Nobel Prize winning neurobiological
      research are integrated for a 30-year update of Milton H. Erickson's "neuro
      psycho-physiology" of therapeutic hypnosis. Implicit processing heuristics are
      proposed as a more general framework for Erickson's concept of permissive
      indirect suggestions in therapeutic hypnosis and psychotherapy. These
      perspectives are illustrated by utilizing implicit processing heuristics to
      facilitate the four-stage creative process in converting implicit to explicit
      memory in a brain-damaged patient.

PMID- 17444365
TI  - An update on age, hypnotic suggestibility, and gender: a brief report.
AB  - This study assessed the relationship of age and hypnotic suggestibility in an
      effort to partially update the findings of Morgan and Hilgard (1973). A total of
      2,660 undergraduates were administered the Harvard Group Scale of Hypnotic
      Susceptibility, Form A (HGSHS:A; Shor & Orne, 1962) over a 7 year period.
      Consistent with Morgan and Hilgard's results, we found a general trend for
      hypnotic suggestibility scores to decrease from age 17 to 40, and then increase
      thereafter. We also found that female participants scored higher on the HGSHS: A
      compared with males across the various age ranges that we sampled.

PMID- 17444366
TI  - Elucidating Tourette's syndrome: perspectives from hypnosis, attention and self
      regulation.
AB  - Biological psychiatry favors drug treatment over non-pharmacological intervention
      and shapes the way clinicians both treat and understand Tourette's Syndrome (TS).
      However, drug treatments for TS involve side effects and are potentially toxic to
      the central nervous system. Moreover, current pharmacological treatments are
      largely ineffective and at best only provide a modest symptom reduction. In this
      paper, we describe how non-pharmacological treatments such as focused attention
      can modulate, reduce, or indeed entirely eliminate the symptoms of TS as well as
      elucidate the underlying neural mechanisms. Showing that the symptoms of TS are
      susceptible to self-regulatory interventions such as hypnosis, we propose that
      attentional training could be used to both treat the disorder and better
      understand it.

PMID- 17444367
TI  - Protecting your nursing license: scope of practice.

PMID- 17444368
TI  - Retaining the older and experienced nurse in the workplace.

PMID- 17444369
TI  - NLRB issues lead case addressing supervisory status in response to Supreme
      Court's decision in Kentucky River.

PMID- 17444370
TI  - What about patient dignity?

PMID- 17444371
TI  - Case presentation: the febrile traveler.

PMID- 17444372
TI  - Don't doctors deserve a cost of living increase?

PMID- 17444373
TI  - Multidisciplinary care for life after cancer: a survivor's center.
AB  - This article introduces the most recent definition of cancer survivor and the
      empirical data demonstrating the barriers that are often faced by patients
      following cancer treatment. The article then describes a novel use of the
      oncology multidisciplinary care model to address those issues, which is one of
      the first of its kind in the nation. The article is closed with a case example.

PMID- 17444374
TI  - Operating the private health care facility: complying with regulatory, privacy,
      record-keeping and reporting requirements.

PMID- 17444375
TI  - Titanic or "freedom of the seas? Navigating around the icebergs for health care
      in Ontario. A review of the statutes affecting private health care delivery in
      Ontario.

PMID- 17444376
TI  - Private clinics in Ontario: what they are and what they are not clearing the
      muddied waters.

PMID- 17444377
TI  - Regulating telehealth in Ontario--next step in the transformation agenda.

PMID- 17444378
TI  - Use of polarised light as a method of pressure ulcer prevention in an adult
      intensive care unit.
AB  - OBJECTIVE: This single-centred randomised pilot study aimed to examine whether
      the wound-healing properties of polarised light are effective in preventing grade
      II or above pressure ulcers in patients admitted to an adult intensive care unit.
      METHOD: Standard pressure ulcer prevention techniques were applied in both
      research groups. Patients allocated to the test group received supplementary
      treatment with polarised light once daily for 10 minutes (sacral area and both
      heels) starting on the first day after admission. The control group received no
      polarised light. RESULTS: A control group of 13 patients and an intervention
      group of 10 patients were included in the study between 1 March and 1 May 2006.
      There was no statistically significant difference between the groups for
      composition, standard pressure ulcer prevention or pressure ulcer risk.
      Observations revealed a statistically significant difference (p = 0.019) between
      the groups when comparing development of grade II or above sacral or heel
      pressure ulcers. CONCLUSION: Patients treated with polarised light developed
      significantly (p = 0.019) fewer grade II or above sacral or heel pressure ulcers
      when compared with a control group receiving no polarised light. Further research
      is required.

PMID- 17444379
TI  - Can translocated bacteria reduce wound infection?

PMID- 17444380
TI  - Venous leg ulcer treatment and practice--Part 4: Surgery and pharmaceutical
      therapies.

PMID- 17444381
TI  - Management of bioburden with a burn gel that targets nociceptors.
AB  - AIM: To assess the effectiveness of RescuDerm, an amorphous, water-soluble burn
      gel in controlling Pseudomonas aeruginosa growth in rat full-thickness wounds
      contaminated with 10(3), 10(5) or 10(7) CFU/g tissue. METHOD: Wounds were treated
      daily for 72 hours with a placebo gel, a 5% w/w mafenide acetate gel (MAF), or
      with four modalities of RescuDerm application. RESULTS: All RescuDerm treatments
      were equally effective within 24 hours in preventing further Pseudomonas
      aeruginosa growth in wounds contaminated with 10(3) CFU/g tissue. Pseudomonas
      aeruginosa levels remained at or below this baseline count for 72 hours in all
      but one of the RescuDerm treatments. The bioburdens in MAF-treated wounds were
      negligible, averaging 0.14 +/- 0.09 log10 CFU/g tissue. While RescuDerm and MAF
      remained bacteriostatic in wounds contaminated with 10(5) CFU/g tissue, this
      property disappeared at higher bioburdens. CONCLUSION: RescuDerm can be used for
      the management of cutaneous injuries sustained in environments deemed marginally
      or moderately contaminated. Heavily contaminated wounds would require irrigation
      prior to application to reduce their bioburden below 10(5) CFU/g tissue.

PMID- 17444382
TI  - Can cycloidal vibration plus standard treatment reduce lower limb cellulitis
      treatment times?
AB  - OBJECTIVE: This single-centre non-blind randomised controlled trial aimed to
      compare clinical outcomes in terms of recovery time of standard treatment of
      lower limb cellulitis versus standard treatment combined with cycloidal vibration
      (Vibro-Pulse) therapy. METHOD: Thirty-six patients (18 per group) with lower limb
      cellulitis were randomised to receive either standard treatment (intravenous or
      oral antibiotic therapy) and bed rest or standard treatment combined with
      cycloidal vibration treatment three times per day, 30 minutes per treatment. The
      outcome measure was the daily amount of reduction in erythema/cellulitis and
      oedema reduction against time for up to seven days of treatment and the resources
      required. RESULTS: There was a clinically significant difference between the two
      groups, with 66% of the study group fully recovering within the seven days
      compared with 11% of the control group. CONCLUSION: Cycloidal vibration combined
      with standard therapy can significantly reduce cellulitis treatment time. This
      can reduce both hospital bed days and the resources required.

PMID- 17444383
TI  - Bacterial profiling using skin grafting, standard culture and molecular
      bacteriological methods.
AB  - OBJECTIVE: Wound healing can be delayed by the presence of colonising bacteria,
      and in polymicrobial wounds they may act synergistically to the further detriment
      of wound healing. In this pilot investigation, biopsy and swab samples were
      obtained as part of skin-graft operations performed on a chronic venous leg ulcer
      in order to study the spatial microbial diversity and to compare standard
      bacteriological and molecular biological techniques. METHOD: The wound was
      sampled before excision, and sampling was undertaken at multiple locations across
      the wound. Swab samples and biopsies were subjected to culture analysis and 16S
      rRNA polymerase chain reaction (PCR), and to denaturing gradient gel
      electrophoresis (DGGE). RESULTS: Within the wound samples, DGGE identified the
      major wound microflora components and established the extent of local differences
      in bacterial diversity. CONCLUSION: This ongoing investigation has verified DGGE
      as a powerful tool for elucidating the clinical microbiology of a chronic disease
      state. It also suggests that skin graft operations are a novel way of obtaining
      multiple samples for in vivo bacteriology and for establishing the spatial
      distribution of bacteria in the complex micro-environment of chronic wounds.

PMID- 17444384
TI  - A prospective observational study of the efficacy of a novel hydroactive
      impregnated dressing.
AB  - OBJECTIVE: To assess the clinical efficacy, tolerance and acceptance of a novel,
      hydroactive-impregnated dressing (Hydrotul) in the local treatment of acute and
      chronic wounds. METHOD: In a prospective observational study 24 centres in
      France, Belgium, Germany and Austria recruited 74 patients. At each dressing
      change the investigators evaluated the condition of the wound, perilesional skin
      and patient-reported pain. Overall, five dressing changes were documented, or
      until complete healing occurred. The hydroactive properties of the dressing were
      assessed in laboratory tests by measuring fluid absorption capacity and kinetics.
      RESULTS: Patients were treated for an average of 17 days. The wound condition
      improved markedly during the observation period. The wound area covered with
      fibrinous slough decreased from 29% to 14%, epithelialisation increased from 19%
      to 54% and 22 wounds were completely healed by the end of the study. The number
      of patients reporting severe and moderate wound pain decreased from 35% to 19%
      and the proportion of patients without wound pain doubled from 27% to 60%. In
      laboratory tests, Hydrotul absorbed two to three times the amount of fluid
      compared with other impregnated wound dressings and the kinetics of absorption
      was much faster. CONCLUSION: The novel hydroactive impregnated dressing supports
      the healing process in patients with acute and chronic wounds and reduces wound
      pain. The dressing absorbs excess wound exudate while keeping the wound surface
      moist and protecting perilesional skin.

PMID- 17444385
TI  - The bigger picture. Seclusion is a soft word for a harsh practice.

PMID- 17444387
TI  - Matching skills to needs.

PMID- 17444386
TI  - Welfare writes. Proposals for the 'new' mental health Personal Capability
      Assessment.

PMID- 17444388
TI  - Getting a move on.

PMID- 17444389
TI  - Shared standards, sharing care.

PMID- 17444390
TI  - Beyond the label.

PMID- 17444391
TI  - Where can you get a bed for 540 pounds per night?

PMID- 17444392
TI  - Fallout from repeated call-ups.

PMID- 17444393
TI  - Payment. Hospitals gear up for baffle over new round of budget cuts.

PMID- 17444394
TI  - Payment. Who are you, anyway?

PMID- 17444395
TI  - Contract management. Boosting contracts to minority-owned firms.

PMID- 17444396
TI  - Health care for all: universal coverage proposals.

PMID- 17444397
TI  - AARP's Novelli beats the drum for health reform. Interview by Bill Santamour.

PMID- 17444398
TI  - Philanthropy. Mega gifts let hospitals rapidly expand their missions.

PMID- 17444399
TI  - Access & coverage. Hospitals help patients find a medical home.

PMID- 17444400
TI  - Partners' high performance medicine initiative harnesses technology to drive
      improvement.

PMID- 17444401
TI  - Notes from the trail [Part 1].

PMID- 17444402
TI  - Inside the Premier/CMS Pay-for-Performance Project.
AB  - In an H&HN exclusive roundtable discussion, representatives from the five top
      performing hospitals describe what they've learned so far from the Premier/CMS
      Pay-for-Performance Project. For hospitals around the country, so-called value
      based ent will soon be the primary way they get paid by both public and
      commercial insurers. The Premier/CMS participants offer valuable insights--and
      warnings--about the challenges ahead.

PMID- 17444403
TI  - Construction--still booming.
AB  - The 2007 Hospital Building Survey shows no letup in construction. But some
      experts see signs of a slowdown.

PMID- 17444404
TI  - Patient safety in the operating room.
AB  - This month's foldout helps hospitals assess their OR culture and pinpoints where
      breakdowns in communication occur and why they can be deadly. Five risk managers
      describe their priorities and what their executives ought to know.

PMID- 17444405
TI  - SCHIP. Does this model for covering kids have legs?
AB  - The popular federal-state insurance program for kids is caught between
      legislators who want to expand its scope and others who want to rein it in.

PMID- 17444406
TI  - Catching the proton wave.
AB  - Proton therapy is hailed as a huge leap in treating certain cancers. But
      hospitals that want proton centers need deep pockets, lots of land and the right
      staff.

PMID- 17444407
TI  - When providers fail to coordinate care, patients' recovery lags.

PMID- 17444408
TI  - Datapage. Budget fights loom for research agencies.

PMID- 17444409
TI  - Partners in public health.

PMID- 17444410
TI  - Interpretive criteria for mupirocin susceptibility testing of Staphylococcus spp.
      using CLSI guidelines.
AB  - Mupirocin is an antimicrobial agent commonly used to treat staphylococcal
      infection or to eliminate persistent carriage. To date, interpretive criteria
      have not been established to define susceptibility or resistance when performing
      mupirocin susceptibility testing. In this evaluation, using CLSI guidelines, a
      total of 502 staphylococci comprising 219 methicillin-sensitive Staphylococcus
      aureus, 222 methicillin-resistant S. aureus and 61 coagulase-negative
      staphylococci are tested by broth microdilution, disc diffusion and E-test. Disc
      diffusion using 5 microg mupirocin discs was found to be a reliable method to
      distinguish susceptible and resistant strains. Minimum inhibitory concentration
      (MIC) determination was required to differentiate low-level and high-level
      resistance to mupirocin. E-test was found to be an accurate alternative to broth
      microdilution for the routine determination of MIC values of staphylococci to
      mupirocin. Broth microdilution and disc-diffusion results were plotted on a
      scattergram, and error rates were calculated. No errors were found using
      susceptibility criteria of < 4 microg/mL (MIC) and > 19 mm (zone diameter).

PMID- 17444411
TI  - Lack of horizontal gene transfer of methicillin-resistance genetic determinants
      from PBP2a-positive, coagulase-negative staphylococci to methicillin-sensitive
      Staphylococcus aureus using transcutaneous electrical nerve stimulation (TENS).
AB  - Previous research shows that approximately half of the coagulase-negative
      staphylococci (CNS) isolated from patients in the intensive care unit (ICU) at
      Belfast City Hospital were resistant to methicillin. The presence of this
      relatively high proportion of methicillin-resistance genetic material gives rise
      to speculation that these organisms may act as potential reservoirs of
      methicillin-resistance genetic material to methicillin-sensitive Staphylococcus
      aureus (MSSA). Mechanisms of horizontal gene transfer from PBP2a-positive CNS to
      MSSA, potentially transforming MSSA to MRSA, aided by electroporation-type
      activities such as transcutaneous electrical nerve stimulation (TENS), should be
      considered. Methicillin-resistant CNS (MR-CNS) isolates are collected over a two
      month period from a variety of clinical specimen types, particularly wound swabs.
      The species of all isolates are confirmed, as well as their resistance to
      oxacillin by standard disc diffusion assays. In addition, MSSA isolates are
      collected over the same period and confirmed as PBP2a-negative. Electroporation
      experiments are designed to mimic the time/voltage combinations used commonly in
      the clinical application of TENS. No transformed MRSA were isolated and all
      viable S. aureus cells remained susceptible to oxacillin and PBP2a-negative.
      Experiments using MSSA pre-exposed to sublethal concentrations of oxacillin (0.25
      microg/mL) showed no evidence of methicillin gene transfer and the generation of
      an MRSA. The study showed no evidence of horizontal transfer of methicillin
      resistance genetic material from MR-CNS to MSSA. These data support the belief
      that TENS and the associated time/voltage combinations used do not increase
      conjugational transposons or facilitate horizontal gene transfer from MR-CNS to
      MSSA.

PMID- 17444412
TI  - Preventive and protective effects of wild basil in ethanol-induced liver toxicity
      in rats.
AB  - In the present study, preventive and protective effects of Ocimum gratissimum in
      ethanol-induced hepatotoxicity are assessed in albino rats. A methanol extract of
      O. gratissimum leaves is prepared, with a yield of 3.5% (w/w) of the dry weight
      of leaves. Graded doses of the extract (10, 20, 40 and 80 mg/kg body weight),
      together with ethanol (5 gm/kg body weight) are administered orally to
      experimental groups for 30 days. Normal control rats receive distilled water
      only, while rats in an alcohol control group (AC) receive ethanol only for 30
      days. O. gratissimum reduced the level of thiobarbituric acid reactive substance
      in all experimental groups (E1-E4). Alanine transaminase and aspartate
      transaminase levels fell in all experimental groups (E1-E4), but this reduction
      was significant only in groups E3 and E4 (P < 0.05), indicating inhibition of
      lipid peroxidation by free radicals generated after ethanol metabolism. Levels of
      antioxidants also increased. Ascorbic acid and glutathione levels increased in
      all experimental groups (E1-E4; P < 0.05 and P < 0.01, respectively). A
      significant increase in catalase (P < 0.05) was noted only in group E4, although
      an upward trend was noted in all experimental groups. This study shows that O.
      gratissimum prevents free radical damage to the liver and thus protects the organ
      from oxidative stress.

PMID- 17444413
TI  - Polymorphonuclear leucocyte respiratory burst activity correlates with serum zinc
      level in type 2 diabetic patients with foot ulcers.
AB  - Patients with diabetes mellitus (DM) are prone to infection, in part due to
      phagocyte dysfunction and impaired polymorphonuclear (PMN) leucocyte superoxide
      generation. Another frequently mentioned factor in the pathogenesis of infection
      in DM patients is altered zinc status. This study aims to evaluate the
      association between serum zinc level and PMN respiratory burst activity in
      patients with type 2 DM. Thirty-nine type 2 DM patients (19 with foot ulcers) and
      20 healthy controls are studied. Respiratory burst activity is evaluated at
      baseline and in stimulated states by a nitro blue tetrazolium (NBT) reduction
      test. Serum zinc level is evaluated by atomic absorption spectrophotometry.
      Although not statistically significant, PMNs from diabetics with foot ulcers
      appeared to be slightly hyperactivated at the baseline state. The NBT index was
      significantly lower in DM patients with foot ulcers after stimulation. Mean serum
      zinc level was significantly lower in diabetics with foot ulcers compared to
      those without foot ulcers. A significant negative correlation between serum zinc
      level and NBT index at baseline was seen in patients with foot ulcers, but this
      changed to a significant positive correlation after stimulation. These findings
      may be explained by PMN hyperactivity at baseline and by respiratory burst
      dysfunction following stimulation in diabetic patients.

PMID- 17444414
TI  - Human papillomavirus prevalence and genotypes in an opportunistically screened
      Irish female population.
AB  - This study aims to evaluate human papillomavirus (HPV) prevalence and
      predominating genotypes in liquid-based cervical cytology samples from an Irish
      urban female population. In addition to use of routine cervical cytology testing,
      women are screened for HPV using the MY09/11 primers for the HPV L1 gene and
      primers for beta-globin amplification in a multiplex format. Overall, 996 women
      between the ages of 16 and 72 years (average age: 35) are included in the study
      and HPV prevalence was 19.8%. Cytology results showed that 88.9% were normal, 9%
      borderline or mild dyskaryosis, 1.1% moderate dyskaryosis and 0.9% severe
      dyskaryosis. Human papillomavirus prevalence in women under 25 was 31%, reducing
      to 23% in women in the 25-35 age group and to 11% in women over 35. Human
      papillomavirus prevalence increased with grade of cytology from 11.4% (normal)
      through 85.4% (borderline), 84% (mild), 100% (moderate) to 100% (severe
      dyskaryosis). HPV 16 (20%) and 18 (12%) were the most common high-risk types
      detected in the study. Other common high-risk types were (in descending order)
      HPV 66, 33, 53, 31 and 58. HPV 66 was associated with the detection of borderline
      abnormalities by cytology. This is the first population-based study of HPV
      prevalence in the normal healthy cervical screening population in the Republic of
      Ireland.

PMID- 17444415
TI  - Antioxidant status in advanced cervical cancer patients undergoing neoadjuvant
      chemoradiation.
AB  - Cervical cancer is the most common cancer in Indian women. The aim of this study
      is to assess the alterations in the circulating lipid peroxide, antioxidant
      components and activities of defence enzymes in advanced cervical cancer
      patients, and to monitor the variations in their levels before and after
      neoadjuvant chemoradiation. Sixty patients with advanced cancer of the cervix
      (FIGO IIIa-IVb) are included in the study, along with 60 healthy controls. Blood
      samples are collected before the start of therapy (S1), two weeks after the
      second course of chemotherapy (S2) and two weeks after completion of
      tele/brachyradiation (S3). Single blood samples are taken from controls. Lipid
      peroxides, conjugated dienes, reduced glutathione (GSH), catalase (CAT) and
      glutathione-S-transferase (GST) are estimated using standard methods. Glutathione
      peroxidase (GPx) and superoxide dismutase (SOD) are assayed using commercially
      available kits. The pretreatment levels of plasma lipid peroxide were
      significantly elevated in cancer patients, while significantly lowered levels of
      GSH, GPx, GST, SOD and CAT were observed when compared to controls. After
      chemotherapy, the levels of lipid peroxidation showed a significant decline (P <
      0.05), which became highly significant after chemoradiation (P < 0.01). Levels of
      GSH, GPx, SOD, GST and CAT showed a mild increase after chemotherapy. After
      chemoradiation, levels reverted to normal or near normal (P < 0.01). Low levels
      of antioxidants in the circulation of patients with cervical cancer may be due to
      their increased utilisation to scavenge lipid peroxidation as well as their
      sequestration by tumour cells. The observed increase in antioxidant concentration
      after therapy might be due to the death of tumour cells or the arrest of tumour
      growth by chemotherapeutic agents. The normalisation of these parameters may
      provide information about the efficacy of neoadjuvant chemoradiation. A larger
      patient cohort with a longer follow-up period for therapeutic response studies
      may yield more significant data.

PMID- 17444416
TI  - Cervical cancer and human papillomavirus among slum dwellers in India.
AB  - Almost half a million new cases of cervical cancer are diagnosed each year
      worldwide. Human papillomavirus is recognised as one of the leading causes and is
      associated with 90% of cases. However, other risk factors (e.g., age of first
      sexual contact, number of sexual partners, multiparity, diet, genetic
      predisposition and environment) are also associated with cervical cancer. The
      present retrospective study is performed on a cohort of women from the slums of a
      major Indian city. The patients are aged between 38 and 68 years (mean: 49.3
      years) and are multiparous (mean number of children: 3.4). In this group, 61%
      have a history of miscarriages. Histological sections from cone biopsy are tested
      for the presence of high-grade human papillomavirus (HPV) using GP5+/GP6+ and
      MY09/MY11 primers and a set of beta3-globin primers. Only 33% of the cancer
      patients studied were positive for high-grade HPV DNA, suggesting that
      predisposition to cervical cancer in this cohort is not highly associated with
      HPV, and that other risk factors may increase the risk of cervical cancer.

PMID- 17444417
TI  - Quantitative analysis of human leucocyte antigen expression during culture of
      Epstein-Barr virus-transformed cell lines using the dako QIFIKIT.
AB  - Pre-existing donor-specific human leucocyte antigen (HLA) antibodies in renal
      allograft recipients result in hyperacute and accelerated graft failure. These
      antibodies can be detected in flow cytometric assay systems using HLA
      characterised Epstein-Barr virus (EBV)-transformed B-lymphocyte cell lines.
      Confident assay performance is predicated by the expression of HLAs on the EBV
      transformed B-cell line surface. Surface HLA expression of three EBV-transformed
      B-cell lines that had previously been used as part of a potential organ recipient
      serum screening panel at St James' University Hospital, Leeds, are assessed for
      changes in the level of HLA expression over the nominal culture duration of eight
      days using the QIFIKIT (Dako, Denmark), a quantitative flow cytometry kit for
      assessing cell surface antigens. A comparison of the mean fluorescence intensity
      (MFI) of the known antigen levels of the beads via a calibration graph permits
      determination of the antibody binding capacity of the cell lines. Results showed
      that HLA expression is not consistent throughout the cell culture, with optimal
      expression occurring during day 2 of culture. Inconsistent HLA expression
      demonstrated during the cell culture means that no assumption of the level of HLA
      expression can be made, and that cell lines used as part of a screening panel
      should have their HLA expression in cell culture determined.

PMID- 17444418
TI  - Erythrocyte oxidative stress in clinical management of diabetes and its
      cardiovascular complications.
AB  - Diabetes mellitus is a chronic disease in its own right and is also regarded as a
      cardiovascular risk factor as well as a cardiovascular disease, due to its
      ability to progress to a stage of cardiovascular co-morbidity. The
      pathophysiology of cardiovascular complications in diabetes is reported to
      involve hyperglycaemia-induced oxidative stress. The erythrocyte has an array of
      endogenous antioxidants involved in quenching oxidant production and the
      exponential chain reactions in diabetes. When the erythrocyte is oxidatively
      stressed, as demonstrated by depleted reduced glutathione and/or increased
      malondialdehyde in its cell membrane, the risk of diabetes progression and its
      cardiovascular sequelae, including atherosclerosis and coronary artery disease,
      is increased. Virtually all studies that determined erythrocyte malondialdehyde
      and glutathione in diabetes show consistently increased and reduced levels,
      respectively. Furthermore, cardiovascular complications of diabetes are reported
      to commence at the prediabetes stage. Current coronary artery disease screening
      programmes based on the presence of two or more risk factors are failing to
      identify those with increased risk of diabetes and cardiovascular complications,
      thereby limiting early interventions. Screening that includes erythrocyte
      oxidative stress determination may provide an additional marker for both
      preclinical and advanced disease. In this review, a concise description of the
      involvement of erythrocyte oxidative stress in diabetes mellitus and its
      cardiovascular sequelae is presented. Antioxidant action and interaction in the
      erythrocyte are also described, with emphasis on why current coronary artery
      disease screening markers cannot be regarded as erythrocyte oxidative stress
      markers.

PMID- 17444419
TI  - The case for oxygen-ozonetherapy.
AB  - Ozone is a very reactive gas that is toxic to the respiratory system. However,
      under controlled conditions, it can be therapeutically useful in several human
      diseases. An unfavourable combination of factors (ozone is one of the worst
      troposphere pollutants) and past misuse have led to misgivings about
      ozonetherapy. However, basic and clinical work developed over the past 10 years
      has clarified the fundamental mechanisms of action of ozone in biology and
      medicine. Interestingly, judicious doses of ozone dissolved in blood trigger a
      cascade of well-defined chemical compounds acting on multiple cellular targets
      according to well-known molecular, biochemical and pharmacological pathways.
      Ozonetherapy is proving to be very useful in age-related macular degeneration,
      ischaemic and infectious diseases, and in wound healing disorders, where
      conventional medicine has failed. Critical evaluation of the potential
      therapeutic utility of this simple, inexpensive medical application by national
      and international health authorities is warranted and may lead to clinical
      benefit for a large proportion of the world's population.

PMID- 17444420
TI  - Nicotine decreases the cytotoxicity of doxorubicin towards MCF-7 and KB-3.1 human
      cancer cells in culture.
AB  - The harmful effects of tobacco use and nicotine are well known. There is strong
      epidemiological evidence for smoking as a risk factor for cancer of the lung and
      oral cavity. The evidence for second-hand smoke as a risk factor for breast
      cancer is rapidly accumulating. The anthracycline doxorubicin is used in the
      treatment of many types of malignancies, including breast cancer. The effect of
      nicotine on doxorubicin toxicity was evaluated in MCF-7 and KB-3.1 cancer cell
      cultures. Nicotine partially inhibited doxorubicin toxicity towards MCF-7 and KB
      3.1 cells, as judged by clonogenicity and flow cytometry assays. Flow cytometric
      analysis showed that < 10% of cells treated with doxorubicin underwent apoptosis,
      while necrosis was the major mode of cell death. Inhibition of apoptosis and
      necrosis in cancer cells by nicotine can diminish the effectiveness of
      doxorubicin in cancer therapy.

PMID- 17444421
TI  - Smoking, fibrinogen and cancer mortality.
AB  - Associations of race, smoking history and fibrinogen levels with cancer mortality
      were investigated prospectively using the ARIC study. Our cohort consisted of
      14,320 participants aged 45-64 at baseline. In an adjusted Cox regression, black
      current heavy smokers (> or = 15 cigarettes per day) demonstrated higher risk of
      respiratory/intrathoracic organ cancer mortality than nonblack current heavy
      smokers. Black former heavy smokers were also found to be at an increased risk of
      respiratory/intrathoracic organ cancer mortality when compared to nonblack former
      heavy smokers. Elevated fibrinogen levels were associated with an increased risk
      of respiratory/intrathoracic organ cancer mortality. Compared to fibrinogen < 259
      mg/dl, fibrinogen 294-335 mg/dl had an adjusted hazard ratio of 3.68 (95% CI:
      1.80-7.55), and fibrinogen > or = 336 mg/dl had an adjusted hazard ratio of 3.78
      (95% CI: 1.84-7.75). Fibrinogen was also a predictor of other types of cancer
      mortality among black participants, but not among nonblack participants. For 10
      race/smoking history categories, fibrinogen levels ranged from a mean of 287
      mg/dl for nonblack former light smokers to a mean of 338 mg/dl for black current
      heavy smokers. Smokers had higher fibrinogen levels than nonsmokers, and black
      smokers had higher fibrinogen levels than nonblack smokers. Smoking carries high
      risks of cancer mortality for African Americans. A factor that needs to be
      considered in the overall assessment of risk is fibrinogen level, which has been
      linked to angiogenesis and metastases of tumors.

PMID- 17444422
TI  - Attitudes and beliefs about smoking among African-American college students at
      historically black colleges and universities.
AB  - Smoking rates are lower among African Americans compared to Caucasians, but
      African Americans have higher lung cancer mortality. Guided by the Powe Fatalism
      Model, this descriptive study reports on attitudes and beliefs and predictors of
      lifetime cigarette smoking behaviors among students at historically black
      colleges and universities (HBCUs). Data were collected using the Attitudes and
      Beliefs about Perceived Consequences of Smoking Scale and a Demographic Data
      Questionnaire. The majority (N = 438) were female and single. More than 50%
      reported trying cigarettes in their lifetime and reported smoking a whole
      cigarette at age 15.5 years. Only 7.5% of the sample were lifetime smokers. The
      likelihood that a student would smoke was 15 times greater if their friends
      smoked and almost seven times greater if they were not members of a Greek
      organization compared to other students. Males associated smoking with self
      confidence, endorsed the emotional benefits and influencing factors of smoking
      compared to females. Intervention efforts should focus on preventing the
      initiation of smoking as well as cessation efforts for students at HBCUs. Campus
      clubs and organizations can play a vital role in long-term changes in smoking
      behaviors for these students.

PMID- 17444423
TI  - Urban poverty and infant mortality rate disparities.
AB  - This study examined whether the relationship between high poverty and infant
      mortality rates (IMRs) varied across race- and ethnic-specific populations in
      large urban areas. Data were drawn from 1990 Census and 1992-1994 Vital
      Statistics for selected U.S. metropolitan areas. High-poverty areas were defined
      as neighborhoods in which > or = 40% of the families had incomes below the
      federal poverty threshold. Bivariate models showed that high poverty was a
      significant predictor of IMR for each group; however, multivariate analyses
      demonstrate that maternal health and regional factors explained most of the
      variance in the group-specific models of IMR. Additional analysis revealed that
      high poverty was significantly associated with minority-white IMR disparities,
      and country of origin is an important consideration for ethnic birth outcomes.
      Findings from this study provide a glimpse into the complexity associated with
      infant mortality in metropolitan areas because they suggest that the factors
      associated with infant mortality in urban areas vary by race and ethnicity.

PMID- 17444424
TI  - New therapeutic options for treating type-2 diabetes: a review of insulin analogs
      and premixed insulin analogs.
AB  - There is a growing consensus that blood glucose control, and postprandial control
      in particular, must become more aggressive if we are to stem the growing tide of
      diabetes-related complications and mortality. For most patients, this means that
      insulin therapy must begin earlier and that insulin must be titrated sufficiently
      to achieve tighter glycemic targets. The limitations of traditional treatment
      regimens, delivery devices and conventional insulin formulations, in conjunction
      with patient factors, have prevented the majority of people with type-2 diabetes
      from realizing the potential benefits of insulin therapy and achieving
      recommended glycemic targets. Fortunately, modern insulin analog formulations,
      new treatment regimens, and advanced delivery devices are now available. This
      review will discuss features of these new tools, and compare the benefits of
      using premixed insulin versus a basal-only approach to initiating insulin
      therapy. Once physicians become familiar with these tools and incorporate them
      into daily practice, they will be able to better tailor diabetes self-management
      programs to the needs of individual patients. The result will be that more
      patients should be able to reach recommended glycemic targets with greater
      convenience and safety than has previously been available.

PMID- 17444425
TI  - NEEMA: a school-based diabetes risk prevention program designed for African
      American children.
AB  - OBJECTIVE: To conduct formative assessment and preliminary biological impact of a
      school-based diabetes risk prevention program for African-American children
      during a 14-week study. METHODS: NEEMA is a school-based diabetes prevention
      program tailored for African-American children. The NEEMA is implemented via four
      social networks-classroom (Health and Physical Education Class), after school
      (Health Club), home (Family Fun Fair) and school cafeteria (Food Service
      Program). Formative assessment data were collected through semistructured
      interviews with physical education (PE) teachers and a pre-to-post design was
      used to measure biological impact. Fasting capillary glucose, height, weight,
      body mass index, percent body fat and fitness data were collected from a sample
      of 58 fourth-grade students. The six elementary schools had > 40% African
      American enrollment and were located in low-income neighborhoods. RESULTS: Face
      to-face interview data revealed diabetes, obesity and food insufficiency as major
      health concerns among PE teachers. Teachers also cited large classes and short PE
      periods as major challenges for implementing the program. From baseline to follow
      up, fitness laps increased from 16.40 (SD = 9.98) to 23.72 (SD = 14.79) (p <
      0.000), fasting capillary glucose decreased from 89.17 mg/dl (SD = 10.05) to
      83.50 mg/dl (SD = 11.26) (p < 0.000), and percent body fat decreased from 27.26
      (SD=12.89) to 26.68 (SD = 11.67) (p < 0.537). CONCLUSION: The NEEMA pilot study
      provided teacher feedback useful for revising the NEEMA health curricula and
      positive preliminary impact of the NEEMA PE class on children's fitness and blood
      glucose levels.

PMID- 17444426
TI  - Facilitating quality improvement in physician management of comorbid chronic
      disease in an urban minority practice.
AB  - CONTEXT: Increasing numbers of patients with multiple chronic conditions present
      in the primary care setting and pose a challenge to physicians who must cope with
      competing demands while adhering to clinical practice guidelines. PURPOSE: We
      tested a chart audit tool to assess how physicians are managing patients with
      multiple comorbidities in an inner-city family medicine practice serving minority
      patients. METHODS: We developed an evidence-based comorbidity chart audit tool
      that captures the number of diagnosed, coexisting general medical conditions and
      adherence to key clinical practice guidelines for each condition. A randomized
      chart audit was undertaken, with one in every five charts selected, yielding a
      total of 314 patient charts. FINDINGS: The majority of patients (59%) had > or =
      2 comorbid chronic conditions, and 32% had > or = 3 comorbid chronic conditions.
      The highest overall adherence to guidelines was for chronic obstructive pulmonary
      disease (90%) and asthma (80%), followed by congestive heart failure (75%) and
      coronary artery disease (58%). For all other conditions, overall adherence to
      guidelines was < or = 50%. CONCLUSIONS: The chart review tool identified
      inconsistencies in adherence to guidelines across multiple diagnosed conditions,
      suggesting the importance of adopting a patient-centered approach to management
      as well as prevention.

PMID- 17444427
TI  - Characteristics of patients with chronic hepatitis-B virus infection in an urban
      hospital.
AB  - BACKGROUND: In the United States, among patients with hepatocellular carcinoma
      (HCC) and portal hypertension from chronic hepatitis-B virus infection, 44% were
      Hispanic and 28% were African American. Because our institution (Bronx Lebanon
      Hospital Center, Bronx, NY) predominantly serves these populations, we studied
      retrospectively the characteristics of patients with chronic hepatitis-B virus
      infection. METHODS: We reviewed the medical records of all patients aged > 18
      years with chronic hepatitis-B virus infection who had been evaluated at our
      institution between January 1, 2002 and May 31, 2005. RESULTS: We identified 167
      patients with chronic hepatitis-B virus infection. Only 12 (7%) patients
      underwent chronic hepatitis-B virus treatment. One-hundred-forty-six (87%)
      patients without decompensated liver cirrhosis were not treated owing to the
      following reasons: normal alanine aminotransferase level (86%), active injection
      drug or heavy alcohol use (9%), lack of health insurance coverage (3%) and
      noncompliance with visits during the evaluation period (2%). HCC screening was
      performed in 78 patients (47%). Lack of insurance coverage and compliance issues
      were predictors for HCC screening (p = 0.04 and p < 0.001, respectively).
      CONCLUSIONS: In the South Bronx, 87% patients were not considered candidates for
      hepatitis-B virus treatment because of normal alanine aminotransferase levels and
      the interference of potentially modifiable social factors. Only 47% of our
      patients with chronic hepatitis-B virus infection underwent HCC screening because
      of lack of insurance coverage and compliance issues.

PMID- 17444428
TI  - Hepatitis-C prevalence in an urban native-American clinic: a prospective
      screening study.
AB  - BACKGROUND: Native-American populations are disproportionately burdened by
      chronic liver disease, and the prevalence of hepatitis C (HCV) in native
      Americans is unknown. PURPOSE: To determine the prevalence of hepatitis C in a
      local native-American population via a prospective screening study. PROCEDURES:
      Two-hundred-forty-three native Americans (161 females/82 males) using an urban
      clinic and representing > 30 tribes from across the United States were screened.
      Mean age was 41 +/- 1 years. Hepatitis-C screening was by anti-HCV with
      confirmation by HCV RNA. A questionnaire assessed potential risk factors for HCV.
      FINDINGS: Anti-HCV antibodies were found in 11.5% (95% CI: 7.5-15.5%). HCV RNA
      was present by polymerase chain reaction (PCR) in 8.6% (95% CI: 5.1-12.1%) and
      was more common in males [13.4% (95% CI: 6.0-20.8%)] than females [6.2% (95% CI:
      2.5-9.9%)]. The most common potential risk factors for chronic HCV infection were
      intravenous (IV) drug or cocaine use (p < 0.0001), tattoos > 5 years old (p <
      0.0001) and having a sexual partner with HCV (p = 0.0063). CONCLUSION: HCV
      prevalence is higher in an urban native-American clinic population than reported
      in the general U.S. population. Use of IV drugs is the most prevalent risk
      factor, but tattoos and sexual transmission may also be important.

PMID- 17444429
TI  - Mobile mammography: assessment of self-referral in reaching medically underserved
      women.
AB  - BACKGROUND: Mobile mammography can be useful in reaching medically underserved
      women. However, it is not known whether self-referral for mobile mammography is
      the best approach for reaching the most vulnerable populations. OBJECTIVES: 1) To
      describe the community outreach patterns of a county-sponsored mobile mammography
      unit, 2) To characterize the follow-up patterns for women with abnormal screening
      mammograms, and 3) to identify reasons why women screened on mobile units seek
      follow-up care outside of the safety-net system. METHODS: We prospectively
      followed women aged > or = 40 years who received mobile mammograms using
      electronic records and medical chart review, and surveyed women who had no
      evidence of diagnostic follow-up. We also reviewed administrative records to
      determine outreach patterns of the mobile mammography units. RESULTS: Seventy
      five percent of mobile visits were with community-based organizations or
      community health centers. At least one quarter of women chose to follow-up
      outside of the safety-net for evaluation of abnormal screening mammograms. Of
      these, nearly 40% reported having insurance or a private physician as the primary
      reason for having diagnostic evaluation outside of the public hospital system.
      CONCLUSIONS: Despite serving primarily community-based facilities, self-referral
      for mobile mammography may not optimally target medically underserved women most
      in need of breast cancer screening.

PMID- 17444430
TI  - Healthcare practices among blacks and whites with urinary tract symptoms.
AB  - CONTEXT: The reasons for African-American men to seek care for lower urinary care
      symptoms has not been determined due to sparse population-based data. OBJECTIVE:
      Our study examines the solicitation and receipt of medical care for urinary
      symptoms among racially oversampled elderly urban and rural cohort of African
      Americans and whites. DESIGN: Longitudinal analyses were conducted on five North
      Carolina counties through the Piedmont Health Survey of the Elderly Established
      Populations for the Epidemiological Study of the Elderly. In 1994, the analytic
      cohort included 482 African Americans and 407 whites; by 1998, 249 and 222,
      respectively. RESULTS: In 1994, 49.4% of African Americans presented with lower
      urinary tract symptoms compared to 56.8% of whites. By 1998, these percentages
      increased to 60.6% and 70.3%, respectively. African Americans reported more
      interference with activities of daily living than whites. African Americans were
      less likely than whites to have regular digital rectal exams (DRE) and were more
      likely to have never received a DRE at all. Additionally, elders with less
      educational attainment, those who smoked, those who delayed care quite often and
      those who used less-experienced physicians were less likely to receive regular
      DREs. CONCLUSION: Poor health behavior has the greatest impact on healthcare
      seeking for lower urinary tract symptoms. These health behavior risk factors are
      systemic of a lack of health education. Increases in health education among
      African Americans regarding lower urinary tract symptoms may close the racial
      disparity in healthcare-seeking behaviors.

PMID- 17444431
TI  - History of fractures as predictor of subsequent hip and nonhip fractures among
      older Mexican Americans.
AB  - OBJECTIVE: To examine the association between previous fracture and risk of new
      hip and nonhip fractures over a seven-year period among older Mexican Americans.
      METHOD: Data used are from the Hispanic Established Population for the
      Epidemiological Study of the Elderly (H-EPESE) (1993-2001). Measures included
      history of previous fracture (hip fracture only, a nonhip fracture, hip and
      nonhip fractures, and no fractures), sociodemographic factors, smoking status,
      medical conditions (arthritis, diabetes, stroke and cancer), activities of daily
      living disability, and high depressive symptoms. Cox proportional regression
      model was used to estimate the seven-year incidence of fractures. RESULTS: Of the
      2,589 subjects, 42 reported a hip fracture, 328 reported a nonhip fracture, and
      2,219 did not report a fracture at baseline. After controlling for all
      covariates, the hazard ratio (HR) of new hip fracture at seven-year follow-up was
      6.48 (95% CI: 3.26-12.97) for subjects with only hip fracture at baseline and
      1.96 (95% CI: 1.22-3.16) for subjects with nonhip fracture at baseline. The HR of
      new nonhip fracture was 1.90 (95% CI: 0.96-3.77) for subjects with only hip
      fracture at baseline and 2.62 (95% CI: 1.95-3.52) for subjects with nonhip
      fracture at baseline. CONCLUSIONS: A previous history of fractures in older
      Mexican Americans is the strongest predictor of recurrent fractures at hip and
      nonhip sites, independent of other health measures. Our findings of recurrent
      fractures suggest the need for more aggressive detection and adequate treatment
      of osteoporosis- and fall-related factors in this population.

PMID- 17444433
TI  - Prime Time Sister Circles: evaluating a gender-specific, culturally relevant
      health intervention to decrease major risk factors in mid-life African-American
      women.
AB  - PURPOSE: To evaluate the effectiveness of Prime Time Sister Circles (PTSC), a
      curriculum-based, culture- and gender-specific health intervention, in assisting
      mid-life African-American women to decrease the major risk factors of physical
      inactivity, poor nutrition and stress. METHODS: One-hundred-thirty-four African
      American women were involved in 11 sites across the country in PTSC and
      comparison groups. PTSC uses a cognitive behavioral modality based on three
      theoretical approaches to reduce risk factors and promote positive health
      changes. Pretest and posttest (10 weeks, and six and 12 months) data were
      collected on various indicators. RESULTS: t test analyses demonstrated a
      statistically significant increase in the women's involvement in physical
      activity at 10 weeks, and six and 12 months. A significant 10-week difference was
      found in the women's diet, with them reporting eating more nutritious foods,
      t(77) = 3.32, p < 0.001. The women also indicated from pretest to 10 weeks, and
      six and 12 months that they changed what they ate to prevent disease (40.4%,
      62.8%, 97.5% and 100%, respectively). A majority of the women at 10 weeks (62.7%)
      and 12 months (65.9%) reported utilizing stress management strategies. There was
      also a 60% increase in yearly mammograms and a 54% increase in blood pressures
      checks. Finally, 83.7% of the women at 12 months felt that the positive changes
      could be maintained over their lifetime. CONCLUSIONS: This study demonstrates the
      effectiveness of PTSC in modifying health-related knowledge, attitudes and
      certain high-risk behaviors in mid-life African-American women.

PMID- 17444432
TI  - The associations of gender, sexual identity and competing needs with healthcare
      utilization among people with HIV/AIDS.
AB  - Studies report gender differences in medical service utilization among persons
      with HIV, although most compare women to heterogeneous groups of men. Competing
      needs for medical care of women may contribute to those differences. We examined
      prospectively the role that competing social, economic and health needs, such as
      caring for others, play in gender differences in hospital, ambulatory and
      emergency room (ER) visits. We considered sexual identity to study women,
      gay/bisexual men and heterosexual men in the most recent wave (n = 1,385) of the
      HCSUS, a nationally representative sample of persons with HIV/AIDS in care in the
      United States. We considered gay/bisexual men and heterosexual men separately
      because their different resources and social networks may lead to disparate
      service utilization. Multivariate regression showed that women were more likely
      than gay/bisexual men to be hospitalized, while women and gay/bisexual men were
      more likely than heterosexual men to use the ER without subsequent
      hospitalization. Controlling for competing needs eliminated neither difference
      but predicted hospitalization and ER use. Findings suggest that addressing
      competing needs could reduce unnecessary hospitalization and ER use for both
      genders. Furthermore, examinations of gender differences in service use should
      include sexual identity.

PMID- 17444434
TI  - Is food love?

PMID- 17444435
TI  - Implementing a diabetes prevention program in a rural African-American church.
AB  - OBJECTIVES: The purpose of this study was to determine the feasibility of
      implementing a diabetes prevention program (DPP) in a rural African-American
      church. METHODS: A six-session DPP, modeled after the successful National
      Institutes of Health (NIH) DPP, was implemented in a rural African-American
      church. Adult members of the church identified as high risk for diabetes, based
      on results of a risk questionnaire, were screened with a fasting glucose. Persons
      with prediabetes, a fasting glucose of 100-125 mg/dL, participated in the six
      session, Lifestyle Balance Church DPP. The primary outcomes were attendance rates
      and changes in fasting glucose, weight and body mass index measured at baseline,
      six- and 12-month follow-up. RESULTS: Ninety-nine adult church members were
      screened for diabetes risk. Eleven had impaired fasting glucose. Ten of 11
      participated in the six-session intervention, for an attendance rate of 78%.
      After the intervention and 12-month follow-up, there was a mean weight loss of
      7.9 lbs and 10.6 lbs, respectively. CONCLUSIONS: This pilot project suggests that
      a modified six-session DPP can be translated to a group format and successfully
      implemented in a church setting. Further randomized studies are needed to
      determine the effectiveness of such an intervention.

PMID- 17444437
TI  - Hormone therapy redeemed.

PMID- 17444436
TI  - Public health preparedness for diverse populations and communities.

PMID- 17444438
TI  - Trusts hail 178m pounds windfall as 'unfair' finance system is axed.

PMID- 17444439
TI  - Acutes accused over discharge info.

PMID- 17444440
TI  - RAB axed as Hewitt defends year of pain.

PMID- 17444441
TI  - On the lost art of analysis.

PMID- 17444442
TI  - Brown's equality drive must begin at birth.

PMID- 17444443
TI  - Data briefing. Did the extra money go on new staff?

PMID- 17444444
TI  - Mental Health. In search of a blueprint.
AB  - Some PCTs are also providing mental health services, at odds with the policy of
      being commissioners only. PCTs are trying different models for mental health
      services, raising provision and care pathway issues. One compromise could be to
      put the provider at arm's length within the organisation.

PMID- 17444445
TI  - Admissions. EARLI impact on acute admissions.

PMID- 17444446
TI  - Special report: ISTCs. Opportunity knocks.
AB  - Independent sector treatment centres can be a force for innovation, improvement
      and value in the NHS. Despite accusations that ITSCs have an unfair advantage,
      they will eventually operate at tariff. ITSCs' independence means they are better
      placed than NHS bodies to use international best practice.

PMID- 17444447
TI  - Commercial management. Profit from preparation.

PMID- 17444448
TI  - Coding cues. Diabetes diagnoses.

PMID- 17444449
TI  - Malpractice consult. Your first line of defense.

PMID- 17444450
TI  - You can turn your practice around. This internist overhauled a struggling
      practice and boosted earnings 47 percent and she's not finished yet.

PMID- 17444451
TI  - When a doctor wants to work part time. Here's how to keep things humming when a
      colleague steps off the partnership track to smell the roses.

PMID- 17444452
TI  - EHRs. The Feds get something right. Doctors have nothing but praise for a
      government program that helps them adopt electronic health records.

PMID- 17444453
TI  - When the hearing loss is the doctor's. Technological advances, and the Americans
      with Disabilities Act, are enabling people with hearing loss to succeed as
      physicians.

PMID- 17444454
TI  - The day I saved Baby Doe. It's easy for a "changeover" patient to fall through
      the cracks. The author's glad she went back to check.

PMID- 17444455
TI  - Health Plans. The only game in town? Physicians across the country say that
      health plan consolidation is becoming a serious problem--and Washington needs to
      step in and do something about it.

PMID- 17444456
TI  - Why do we disconnect the dying?

PMID- 17444457
TI  - Participatory research in pediatric palliative care: benefits and challenges.
AB  - Participatory research is an approach wherein all parties concerned play an
      active role throughout the research process, from initial design to the
      interpretation and dissemination of results. This article reports on two
      participatory research projects evaluating a new in-home respite program for
      children requiring pediatric palliative care and their families. Some of the
      realities, benefits, and challenges resulting from a participatory approach to
      research in pediatric palliative care are described. The outcomes of these two
      studies highlight the conclusion that organizations, professionals, volunteers,
      and family members accompanying the dying benefit from a participatory research
      method that actively engages their involvement. This approach offers participants
      the opportunity to voice concerns as well as supports a sense of empowerment.
      From the researcher's point of view, a participatory process can serve to
      increase both the social relevancy and impact of the research.

PMID- 17444458
TI  - Parents' and children's perspectives of a children's hospice bereavement program.
AB  - The provision of some form of bereavement services is an integral part of any
      pediatric hospice program. The Canuck Place hospice program has offered
      bereavement services since it began in 1995. A mixed-method evaluation of the
      impact of the Canuck Place program on the families it served during its first two
      and-a-half years of operation was conducted. The bereavement services reviewed
      included follow-up care for families, and bereavement support groups for children
      and their parents. Eight children were interviewed in the initial phase, and nine
      completed a survey questionnaire; 28 parents rated their level of satisfaction
      with various aspects of their experience with the parent support group. Findings
      indicated that the follow-up component of the program was well-received by family
      members. When assessing their group experiences, children and parents most
      appreciated the support and understanding they received, the freedom to express
      themselves, a diminished sense of isolation, and the normalization of their
      emotions. Practical considerations when offering bereavement support groups are
      discussed in this paper.

PMID- 17444459
TI  - Developing a living with hope program for caregivers of family members with
      advanced cancer.
AB  - A theory-based intervention, the Living with Hope Program (LWHP), was designed to
      foster hope in caregivers of family members with advanced cancer. The LWHP was
      developed from qualitative data and using Harding and Higginson's recommendations
      for family caregiver interventions as a guide. The LHWP is: (a) focused
      specifically on the caregivers themselves, (b) theory based, (c) feasible, (d)
      acceptable, and (e) pilot tested. The program consists of a hope video and a hope
      activity titled Stories of the Present. A mixed-method, concurrent triangulation,
      pre- and post-test design was used to pilot test the LWHP The results of the
      pilot test suggest the LWHP is easy to use, flexible, and feasible, and shows
      promise in increasing hope and quality of life scores in family caregivers.

PMID- 17444460
TI  - Staff stress, work satisfaction, and death attitudes on an oncology palliative
      care unit, and on a medical and radiation oncology inpatient unit.
AB  - Professional caregivers for cancer patients are at high risk for work-related
      stress, but it is not clear how this relates to exposure to death and dying, and
      to professional satisfaction. This study compares work-related stress and staff
      satisfaction on an academic acute palliative care unit (PCU) with that on a
      medical and radiation oncology inpatient unit (OIU) at the same cancer centre.
      PCU staff tended to report less work stress-particularly related to terminal care
      than those on the OIU, and higher work satisfaction and team support. PCU staff
      were more likely to perceive their work experience as having "positively altered
      their attitude to death" (p = 0.007). These results show that a supportive team
      environment can exist on an academic PCU and suggest that support currently
      offered to PCU staff in terms of caring for terminally ill patients should also
      be extended to those working in general oncology settings.

PMID- 17444461
TI  - Is courage the counterpoint of demoralization?
AB  - OBJECTIVE: To consider the role courage plays in our ability to cope with threat
      and adversity, especially the role of courage in understanding demoralization and
      dignity. METHOD: By exploring standard psychiatric texts and Aristotle's concept
      of courage and virtue. A review of Medline and PsycINFO provided few relevant
      documents, reflecting the paucity of research on the concept of courage in
      psychiatry, palliative care, and psycho-oncology. RESULTS AND CONCLUSIONS:
      Courage is an important precursor to maintaining morale and therefore may play a
      critical causative role in demoralization. Courage is also intimately related to
      the concepts of self-esteem, free will, and personal values in life. The utility
      of the concept of courage is that it enables a response to a difficult
      circumstance. The main drawback of courage in a therapeutic sense is that it is
      often linked with cowardice, which has a pejorative connotation and is
      notoriously difficult to diagnose.

PMID- 17444463
TI  - Integrating massage into rural caregiving at end-of-life.

PMID- 17444462
TI  - The role of support staff in pediatric palliative care: their perceptions,
      training, and available resources.
AB  - Pediatric palliative care requires the orchestrated efforts of a
      multidisciplinary care team of medical staff, nursing, psychosocial staff, and
      other healthcare professionals. Augmenting this team are support staff including
      financial counsellors, volunteers, secretaries, and others not involved in the
      direct administration of medical services. Prior research in palliative care has
      studied the perceptions, training, and professional resources of medical staff
      and social workers, but neglected to investigate such factors in support staff.
      Our study examined the effect of involvement in end-of-life pediatric care on
      support staff. We found this community to consist of a heterogeneous population
      of hospital employees, who develop numerous, substantial, direct interactions
      with dying children and their families. They indicated that such experiences had
      caused some adverse outcomes in their lives, and that few felt they had
      sufficient knowledge or training in palliative care. Our respondents voiced
      noteworthy opinions on symptom control, cultural issues, and spirituality
      pertinent to pediatric palliative care. Support staff play a key role in the
      palliative care team; research and resources need to be directed to educating,
      training, and supporting them.

PMID- 17444464
TI  - Evaluation of palliative care at home: the families' perspective.

PMID- 17444465
TI  - Narrating pain in an emergency ward.

PMID- 17444466
TI  - Patient death unwrapped.

PMID- 17444467
TI  - Education and political action--historically intertwined for nursing.

PMID- 17444468
TI  - Creating innovative models for education.

PMID- 17444470
TI  - Redefining nursing perceptions: becoming an RN.

PMID- 17444472
TI  - Responding to disaster.

PMID- 17444473
TI  - Lobbying: not a bad word, but a core competency.

PMID- 17444474
TI  - Alphabet soup of healthcare.
AB  - With an increasingly complex health system, one of the challenges that nurses
      face today is understanding the alphabet soup of healthcare regulations. State
      and federal governments and industry regulations heavily govern healthcare and
      how nurses practice. Considering the healthcare industry's current focus on
      quality control, corporate compliance and patient confidentiality, understanding
      regulatory mandates are a must in today's healthcare arena. Here are some of the
      agencies and other organizations that regulate national health issues and affect
      how nurses practice.

PMID- 17444475
TI  - The importance of getting involved: policy and governmental relations at NCSBN.

PMID- 17444477
TI  - Safety and infection control head new inspection agenda.

PMID- 17444476
TI  - Unsupported and outdated: understanding the issues concerning the nursing faculty
      shortage.

PMID- 17444478
TI  - PCTs consider alternative to homeopathic hospitals.

PMID- 17444479
TI  - Early promise turns sour for mental health chiefs.

PMID- 17444480
TI  - On employment and health.

PMID- 17444481
TI  - Who can make the health service listen?

PMID- 17444482
TI  - Barometer. Acute trusts March 2007.

PMID- 17444483
TI  - Manager-doctor relationships. 2 tribes.

PMID- 17444484
TI  - Data sharing. Crossing borders.

PMID- 17444485
TI  - Innovation. Save the day.
AB  - As NHS spending is reduced, trusts will be looking to IT projects to cut costs
      while improving care. The move back to local control of IT programmes gives IT
      managers a chance to influence the projects. Projects will tend to use existing
      systmes rather than costly new kit.

PMID- 17444486
TI  - Race equality. Set out your stall for equality.

PMID- 17444487
TI  - Social entrepreneurs. Taking care of business.

PMID- 17444488
TI  - Multisensory convergence in auditory cortex, II. Thalamocortical connections of
      the caudal superior temporal plane.
AB  - Recent studies of macaque monkey auditory cortex have revealed convergent
      auditory and somatosensory activity in the caudomedial area (CM) of the belt
      region. In the present study and its companion (Smiley et al., J. Comp. Neurol.
      [this issue]), neuroanatomical tracers were injected into CM and adjacent areas
      of the superior temporal plane to identify sources of auditory and somatosensory
      input to this region. Other than CM, target areas included: A1, caudolateral belt
      (CL), retroinsular (Ri), and temporal parietotemporal (Tpt). Cells labeled by
      injections of these areas were distributed mainly among the ventral (MGv),
      posterodorsal (MGpd), anterodorsal (MGad), and magnocellular (MGm) divisions of
      the medial geniculate complex (MGC) and several nuclei with established
      multisensory features: posterior (Po), suprageniculate (Sg), limitans (Lim), and
      medial pulvinar (PM). The principal inputs of CM were MGad, MGv, and MGm, with
      secondary inputs from multisensory nuclei. The main inputs of CL were Po and
      MGpd, with secondary inputs from MGad, MGm, and multisensory nuclei. A1 was
      dominated by inputs from MGv and MGad, with light multisensory inputs. The input
      profile of Tpt closely resembled that of CL, but with reduced MGC inputs.
      Injections of Ri also involved CM but strongly favored MGm and multisensory
      nuclei, with secondary inputs from MGC and the inferior division (VPI) of the
      ventroposterior complex (VP). The results indicate that the thalamic inputs of
      areas in the caudal superior temporal plane arise mainly from the same nuclei,
      but in different proportions. Somatosensory inputs may reach CM and CL through
      MGm or the multisensory nuclei but not VP.

PMID- 17444489
TI  - Distribution of Kv3.3 potassium channel subunits in distinct neuronal populations
      of mouse brain.
AB  - Kv3.3 proteins are pore-forming subunits of voltage-dependent potassium channels,
      and mutations in the gene encoding for Kv3.3 have recently been linked to human
      disease, spinocerebellar ataxia 13, with cerebellar and extracerebellar symptoms.
      To understand better the functions of Kv3.3 subunits in brain, we developed
      highly specific antibodies to Kv3.3 and analyzed immunoreactivity throughout
      mouse brain. We found that Kv3.3 subunits are widely expressed, present in
      important forebrain structures but particularly prominent in brainstem and
      cerebellum. In forebrain and midbrain, Kv3.3 expression was often found
      colocalized with parvalbumin and other Kv3 subunits in inhibitory neurons. In
      brainstem, Kv3.3 was strongly expressed in auditory and other sensory nuclei. In
      cerebellar cortex, Kv3.3 expression was found in Purkinje and granule cells.
      Kv3.3 proteins were observed in axons, terminals, somas, and, unlike other Kv3
      proteins, also in distal dendrites, although precise subcellular localization
      depended on cell type. For example, hippocampal dentate granule cells expressed
      Kv3.3 subunits specifically in their mossy fiber axons, whereas Purkinje cells of
      the cerebellar cortex strongly expressed Kv3.3 subunits in axons, somas, and
      proximal and distal, but not second- and third-order, dendrites. Expression in
      Purkinje cell dendrites was confirmed by immunoelectron microscopy. Kv3 channels
      have been demonstrated to rapidly repolarize action potentials and support high
      frequency firing in various neuronal populations. In this study, we identified
      additional populations and subcellular compartments that are likely to sustain
      high-frequency firing because of the expression of Kv3.3 and other Kv3 subunits.

PMID- 17444490
TI  - Glycine receptors in the striatum, globus pallidus, and substantia nigra of the
      human brain: an immunohistochemical study.
AB  - Glycine receptors (GlyRs) are heteropentameric chloride ion channels that
      facilitate fast-response, inhibitory neurotransmission in the mammalian spinal
      cord and brain. GlyRs have four functional subunits, alpha1-3 and beta, which
      likely exist in heteromeric alphabeta combinations. Mutations in GlyR alpha1 and
      beta subunits are well known for their involvement in hyperekplexia, a paroxysmal
      motor disorder. In this study we present the first detailed immunohistochemical
      investigation at the regional, cellular, and subcellular levels of GlyRs in the
      human basal ganglia. The results show that GlyRs are present at the regional
      level in low concentrations in the striatum and globus pallidus and are present
      in the highest concentrations in the substantia nigra. At the cellular level,
      GlyRs are present only in discrete populations of neurons immunoreactive for
      choline acetyltransferase (ChAT), parvalbumin, and calretinin in the human
      striatum, on a subpopulation of parvalbumin- and calretinin-positive neurons in
      the globus pallidus, and in the substantia nigra GlyRs are present on
      approximately three-fourths of all pars compacta and one-third of all pars
      reticulata neurons. They also form a distinct band of immunoreactive neurons in
      the intermedullary layers of the globus pallidus. At the subcellular level in the
      substantia nigra pars reticulata (SNr), GlyRs show a localized distribution on
      the soma and dendrites that partially complements but does not overlap with the
      distribution of gamma-aminobutyric acid (GABA)A receptors. Our results
      demonstrate the precise cellular and subcellular localization of GlyRs in the
      human basal ganglia and suggest that glycinergic receptors may play an important
      complementary role to other inhibitory receptors in modulating cholinergic,
      dopaminergic, and GABAergic neuronal pathways in the basal ganglia.

PMID- 17444491
TI  - Topographic organization of sensory afferents of Johnston's organ in the honeybee
      brain.
AB  - Johnston's organ (JO) in insects is a multicellular mechanosensory organ
      stimulated by movement of the distal part of the antenna. In honeybees JO is
      thought to be a primary sensor detecting air-particle movements caused by the
      waggling dance of conspecifics. In this study projection patterns of JO afferents
      within the brain were investigated. About 720 somata, distributed around the
      periphery of the second segment of the antenna (pedicel), were divided into three
      subgroups based on their soma location: an anterior group, a ventral group, and a
      dorsal group. These groups sent axons to different branches (N2 to N4) diverged
      from the antennal nerve. Dye injection into individual nerve branches revealed
      that all three groups of afferents, having fine collaterals in the dorsal lobe,
      sent axons broadly through tracts T6I, T6II, and T6III to terminate ipsilaterally
      in the medial posterior protocerebral lobe, the dorsal region of the
      subesophageal ganglion, and the central posterior protocerebral lobe,
      respectively. Within these termination fields only axon terminals running in T6I
      were characterized by thick processes with large varicosities. Differential
      staining using fluorescent dyes revealed that the axon terminals of the three
      groups were spatially segregated, especially in T6I, showing some degree of
      somatotopy. This spatial segregation was not observed in axon terminals running
      in other tracts. Our results show that projection patterns of JO afferents in the
      honeybee brain fundamentally resemble those in the dipteran brain. The possible
      roles of extensive termination fields of JO afferents in parallel processings of
      mechanosensory signals are discussed.

PMID- 17444492
TI  - Molecular heterogeneity of developing retinal ganglion and amacrine cells
      revealed through single cell gene expression profiling.
AB  - During development of the central nervous system (CNS), cycling uncommitted
      progenitor cells give rise to a variety of distinct neuronal and glial cell
      types. As these different cell types are born they progress from newly specified
      cells to fully differentiated neurons and glia. In order to define the
      developmental processes of individual cell types, single cell expression
      profiling was carried out on developing ganglion and amacrine cells of the murine
      retina. Individual cells from multiple developmental stages were isolated and
      profiled on Affymetrix oligonucleotide arrays. Two-color fluorescent in situ
      hybridization on dissociated retinas was used to verify and extend the microarray
      results by allowing quantitative measurements of a large number of cells
      coexpressing two genes. Together, these experiments have yielded an expanded view
      of the processes underway in developing retinal ganglion and amacrine cells, as
      well as several hundred new marker genes for these cell types. In addition, this
      study has allowed for the definition of some of the molecular heterogeneity both
      between developing ganglion and amacrine cells and among subclasses of each cell
      type.

PMID- 17444493
TI  - Mouse olfactory sensory neurons express 10,000 genes.
AB  - Olfactory epithelial cells from olfactory marker protein-green fluorescent
      protein (OMP-GFP) mice were separated by fluorescence-activated cell sorting into
      a GFP+ sample enriched in mature olfactory sensory neurons (OSNs) and a GFP-
      sample enriched in all other cells. GeneChip expression profiling of these
      samples provided a predictive measure of expression in OSNs. Validation tests
      comparing the ratio of GFP+/GFP- signal intensity against expression patterns
      from in situ hybridization for 189 mRNAs proved statistically significant and
      provided probabilities of expression in OSNs scaled according to the signal
      intensity ratios. These probabilities predict that, among 11,596 mRNAs detected
      in the GFP+ sample, more than 10,000 are expressed in OSNs. Transcripts and
      overrepresented categories of mRNAs detected in the GFP+ sample agreed with known
      properties of OSNs and predict additional properties. For example, ciliogenesis
      and spermatogenesis were overrepresented, consistent with similarities between
      OSN cilia and sperm flagella. Chromatin assembly mRNAs were expressed throughout
      the OSN cell lineage, consistent with the hypothesis that chromatin remodeling
      plays a role in OSN differentiation. We detected numerous signaling proteins and
      receptors, such as 30 nonchemosensory G-protein-coupled receptors, including the
      presynaptic glutamate receptor mGlur4 and the Wnt receptor Fzd3. The largest
      group of mRNAs, however, was the hundreds of transcriptional regulators that
      presumably determine the OSN phenotype. The absence of OMP protein in OMP-GFP
      mice had no detectable effect on mRNA abundance. Within limits prescribed by the
      nature of microarray data and the in situ hybridization validation, these data
      should be useful in directing further experiments on OSN function.

PMID- 17444494
TI  - Jumping translocations.
AB  - Jumping translocations (JT) are uncommon constitutional or acquired chromosome
      rearrangements involving one donor and several recipient chromosomes. They occur
      in various pathologic conditions and the mechanism of their formation remains
      elusive. A review of the literature showed that the major localizations of the
      breakpoints of JTs in human samples are nonrandomly located in pericentromeric
      and telomeric regions of chromosomes. Interestingly, comparison of the
      localization of the chromosomal breakpoints and of presence of interstitial DNA
      repeats showed differences between constitutional and acquired JTs suggesting
      differences in the mechanisms for the genesis of JTs and their consequences.

PMID- 17444495
TI  - Unscheduled DNA replication origin activation at inserted HPV 18 sequences in a
      HPV-18/MYC amplicon.
AB  - Oncogene amplification is a critical step leading to tumorigenesis, but the
      underlying mechanisms are still poorly understood. Despite data suggesting that
      DNA replication is a major source of genomic instability, little is known about
      replication origin usage and replication fork progression in rearranged regions.
      Using a single DNA molecule approach, we provide here the first study of
      replication kinetics on a previously characterized MYC/papillomavirus (HPV18)
      amplicon in a cervical cancer. Using this amplicon as a model, we investigated
      the role DNA replication control plays in generating amplifications in human
      cancers. The data reveal severely perturbed DNA replication kinetics in the
      amplified region when compared with other regions of the same genome. It was
      found that DNA replication is initiated from both genomic and viral sequences,
      resulting in a higher median frequency of origin firings. In addition, it was
      found that the higher initiation frequency was associated with an equivalent
      increase in the number of stalled replication forks. These observations raise the
      intriguing possibility that unscheduled replication origin activation at inserted
      HPV-18 viral DNA sequences triggers DNA amplification in this cancer cell line
      and the subsequent overexpression of the MYC oncogene.

PMID- 17444496
TI  - Corticotropin-releasing factor, urocortin 1, and their receptors in the mouse
      spinal cord.
AB  - Corticotropin-releasing factor (CRF) and urocortin 1 (Ucn1) are involved in
      stress adaptation. CRF receptor 1 (CRF1) binds CRF and Ucn1 with similar high
      affinity, but CRF receptor 2 (CRF2) binds Ucn1 with higher affinity than CRF. We
      tested the hypothesis that in the spinal cord CRF and Ucn1 control peripheral
      components of the stress response, by assessing the distribution of CRF- and Ucn1
      containing fibers, CRF1 and CRF2 mRNAs, and CRF receptor protein (CRFR) in the
      mouse spinal cord, by using immunofluorescence and in situ hybridization. CRF,
      Ucn1, and CRFR occurred throughout the spinal cord. CRF fibers predominated in
      laminae I, V-VII, and X of Rexed. Ucn1 fibers occurred mainly in laminae VII and
      X and occasionally in lamina IX. Both CRFR mRNAs occurred in all laminae except
      the superficial laminae of the dorsal horn, but they exhibited different
      distributions, CRF2 mRNA having a wider occurrence (laminae III-X) than CRF1 mRNA
      (laminae III-VIII). Double immunofluorescence indicated that CRF and Ucn1 fibers
      contacted CRFR-containing neurons, mainly in laminae VII and X. The strongest co
      distribution of CRF1 and CRF2 mRNAs with CRF and Ucn1 fibers appeared in lamina
      VII. CRF2 mRNA predominated in lamina IX together with Ucn1, whereas CRF2 mRNA
      predominated in lamina X, where it had similar distributions with each ligand. In
      view of the lamina-specific and similar distributions of the two CRF receptor
      mRNAs with their ligands, we suggest that CRF1 and CRF2 are involved in
      peripheral stress adaptation processes, such as modulation of stress-induced
      analgesia and the mediation of visceral nociceptive information by CRF2.

PMID- 17444497
TI  - GABAergic phenotype of periglomerular cells in the rodent olfactory bulb.
AB  - Periglomerular (PG) cells in the rodent olfactory bulb are heterogeneous
      anatomically and neurochemically. Here we investigated whether major classes of
      PG cells use gamma-aminobutyric acid (GABA) as a neurotransmitter. In addition to
      three known subtypes of PG cells expressing tyrosine hydroxylase (TH), calbindin
      D-28k (CB), and calretinin (CR), we identified a novel PG cell population
      containing the GABAA receptor alpha5 subunit. Consistent with previous studies in
      the rat, we found that TH-positive cells were also labeled with antibodies
      against GABA, whereas PG cells expressing CB or the alpha5 subunit were GABA
      negative. Using GAD67-GFP knockin mice, we found that all PG cell subtypes
      expressed GAD67-GFP. Calretinin labeled the major fraction (44%) of green
      fluorescent protein (GFP)-positive cells, followed by TH (16%), CB (14%), and the
      alpha5 subunit (13%). There was no overlap between these neuronal populations,
      which accounted for approximately 85% of GAD67-GFP-positive cells. We then
      demonstrated that PG cells labeled for TH, CB, or CR established dendrodendritic
      synapses expressing glutamic acid decarboxylase (GAD) or the vesicular inhibitory
      amino acid transporter, VGAT, irrespective of their immunoreactivity for GABA. In
      addition, CB-, CR-, and TH-positive dendrites were apposed to GABAA receptor
      clusters containing the alpha1 or alpha3 subunits, which are found in mitral and
      tufted cells, and the alpha2 subunit, which is expressed by PG cells. Together,
      these findings indicate that all major subtypes of PG cells are GABAergic. In
      addition, they show that PG cells provide GABAergic input to the dendrites of
      principal neurons and are interconnected with other GABAergic interneurons, which
      most likely are other PG cells.

PMID- 17444498
TI  - Ultrastructure of primary afferent terminals and synapses in the rat nucleus of
      the solitary tract: comparison among the greater superficial petrosal, chorda
      tympani, and glossopharyngeal nerves.
AB  - The greater superficial petrosal (GSP), chorda tympani (CT), and glossopharyngeal
      (IX) nerves terminate in overlapping patterns in the brainstem in the rat nucleus
      of the solitary tract (NTS). There is one region, in particular, that receives
      overlapping inputs from all three nerves and is especially plastic during normal
      and experimentally altered development. To provide the requisite data necessary
      ultimately to delineate the circuitry in this region, we characterized the
      morphology of the synaptic inputs provided by the GSP, CT, and IX nerves through
      transmission electron microscopy. Although all three nerves had features
      characteristic of excitatory nerve terminals, ultrastructural analysis revealed
      dimorphic morphologies differentiating IX terminals from GSP and CT terminals. IX
      terminals had a larger area than GSP and CT terminals, and more synapses were
      associated with IX terminals compared with GSP and CT terminals. Additionally, IX
      terminals formed synapses most often with spines, as opposed to GSP and CT
      terminals, which formed synapses more often with dendrites. IX terminals also
      exhibited morphological features often associated with synaptic plasticity more
      often than was seen for GSP and CT terminals. These normative data form the basis
      for future studies of developmentally and environmentally induced plasticity in
      the rodent brainstem.

PMID- 17444499
TI  - Anterior hypothalamic neural activation and neurochemical associations with
      aggression in pair-bonded male prairie voles.
AB  - Male prairie voles (Microtus ochrogaster) display mating-induced pair bonding
      indicated by social affiliation with their female partners and aggression toward
      unfamiliar conspecifics. In the present study, we characterized their aggression
      associated with pair bonding and examined the related neuronal activation and
      neurochemical architecture. Males that were pair-bonded for 2 weeks displayed
      intense levels of aggression toward a female or male conspecific stranger but
      maintained a high level of social affiliation with their familiar female
      partners. These social interactions induced increases in neural activation,
      indicated by increased density of Fos-immunoreactive staining (Fos-ir) in several
      brain regions including the bed nucleus of the stria terminalis (BNST), medial
      preoptic area (MPOA), paraventricular nucleus (PVN), anterior cortical (AcA), and
      medial nuclei (MeA) of the amygdala. In the anterior hypothalamus (AH), increased
      density of Fos-ir staining was found specifically to be associated with
      aggression toward unfamiliar female or male strangers. In addition, higher
      densities of AH cells that were stained for tyrosine hydroxylase (TH) or
      vasopressin (AVP) were also labeled with Fos-ir in these males displaying
      aggression toward a conspecific stranger compared with males displaying social
      affiliation toward their female partner. Together, our results indicate that
      dopamine and vasopressin in the AH may be involved in the regulation of enduring
      aggression associated with pair bonding in male prairie voles.

PMID- 17444500
TI  - Searching for susceptibility alleles: emphasis on bilateral breast cancer.

PMID- 17444501
TI  - Effect of short-term treatment with alendronate on ulnar bone adaptation to
      cyclic fatigue loading in rats.
AB  - Targeted remodeling of fatigue-injured bone involves activation of osteoclastic
      resorption followed by local bone formation by osteoblasts. We studied the effect
      of parenteral alendronate (ALN) on bone adaptation to cyclic fatigue. The ulnae
      of 140 rats were cyclically loaded unilaterally until 40% loss of stiffness
      developed. We used eight treatment groups: (1) baseline control; (2) vehicle
      (sterile saline) and (3) alendronate before fatigue, no adaptation (Pre-VEH, Pre
      ALN, respectively); (4) vehicle and (5) alendronate during adaptation to fatigue
      (Post-VEH, Post-ALN, respectively); (6) vehicle before fatigue and during
      adaptation (Pre-VEH/Post-VEH); (7) alendronate before fatigue and vehicle during
      adaptation (Pre-ALN/Post-VEH); (8) alendronate before fatigue and during
      adaptation (Pre-ALN/Post-ALN). Bones from half the rats/group were tested
      mechanically; remaining bones were examined histologically. The following
      variables were quantified: volumetric bone mineral density (vBMD); ultimate force
      (F(u)); stiffness (S); work-to-failure (U); cortical area (Ct.Ar); new woven bone
      tissue area (Ne.Wo.B.T.Ar); resorption space density (Rs.N/T.Ar). Microcracking
      was only seen in fatigue-loaded ulnae. A significant effect of alendronate on
      vBMD was not found. Preemptive treatment with alendronate did not protect the
      ulna from structural degradation during fatigue. After fatigue, recovery of
      mechanical properties by adaptation occurred; here a significant alendronate
      effect was not found. An alendronate-specific effect on adaptive Ne.Wo.B.T.Ar was
      not found. In the fatigue-loaded ulna, Rs.N/T.Ar was increased in vehicle-treated
      adapted groups, but not alendronate-treated adapted groups, when compared with
      baseline control. These data suggest that short-term alendronate treatment does
      not protect bone from fatigue in this model. Inhibition of remodeling may reduce
      microcrack repair over time.

PMID- 17444502
TI  - New natural history of interferon-beta-treated relapsing multiple sclerosis.
AB  - OBJECTIVE: To investigate the impact of interferon-beta (IFNbeta) on disease
      progression in relapsing-remitting multiple sclerosis patients. METHODS: A cohort
      of 1,504 relapsing-remitting multiple sclerosis (1,103 IFNbeta-treated and 401
      untreated) patients was followed for up to 7 years. Cox proportional hazards
      regression adjusted for propensity score inverse weighting was used to assess the
      differences between the two groups for three different clinical end points:
      secondary progression (SP) and irreversible Expanded Disability Status Scale
      (EDSS) scores 4 and 6. Times from first visit and from date of birth were used as
      survival time variables. RESULTS: The IFNbeta-treated group showed a highly
      significant reduction in the incidence of SP (hazard ratio [HR], 0.38, 95%
      confidence interval [CI], 0.24-0.58 for time from 1st visit; HR, 0.36, 95% CI,
      0.23-0.56 for time from date of birth; p < 0.0001), EDSS score of 4 (HR, 0.70,
      95% CI, 0.53-0.94 for time from first visit; HR, 0.69, 95% CI, 0.52-0.93 for time
      from date of birth; p < 0.02), and EDSS score of 6 (HR, 0.60, 95% CI, 0.38-0.95
      for time from first visit; HR, 0.54, 95% CI, 0.34-0.86 for time from date of
      birth; p < or = 0.03) when compared with untreated patients. SP and EDSS scores
      of 4 and 6 were reached with significant delays estimated by times from first
      visit (3.8, 1.7, and 2.2 years) and from date of birth (8.7, 4.6, and 11.7 years)
      in favor of treated patients. Sensitivity analysis confirmed findings.
      INTERPRETATION: IFN-beta slows progression in relapsing-remitting multiple
      sclerosis patients.

PMID- 17444503
TI  - Interferon-beta for multiple sclerosis: Long-term benefits?

PMID- 17444504
TI  - Environmental risk factors for multiple sclerosis. Part I: the role of infection.
AB  - Although genetic susceptibility explains the clustering of multiple sclerosis
      (MS) cases within families and the sharp decline in risk with increasing genetic
      distance, it cannot fully explain the geographic variations in MS frequency and
      the changes in risk that occur with migration. Epidemiological data provide some
      support for the "hygiene hypothesis," but with the additional proviso for a key
      role of Epstein-Barr virus (EBV) in determining MS risk. We show that whereas EBV
      stands out as the only infectious agent that can explain many of the key features
      of MS epidemiology, by itself the link between EBV and MS cannot explain the
      decline in risk among migrants from high to low MS prevalence areas. This decline
      implies that either EBV strains in low-risk areas have less propensity to cause
      MS, or that other infectious or noninfectious factors modify the host response to
      EBV or otherwise contribute to determine MS risk. The role of infectious factors
      is discussed here; in a companion article, we will examine the possible role of
      noninfectious factors and provide evidence that high levels of vitamin D may have
      a protective role, particularly during adolescence. The primary purpose of these
      reviews is to identify clues to the causes of MS and to evaluate the possibility
      of primary prevention.

PMID- 17444505
TI  - C-terminal titin deletions cause a novel early-onset myopathy with fatal
      cardiomyopathy.
AB  - OBJECTIVE: The giant protein titin is essential for striated muscle development,
      structure, and elasticity. All titin mutations reported to date cause late-onset,
      dominant disorders involving either skeletal muscle or the heart. Our aim was to
      delineate the phenotype and determine the genetic defects in two consanguineous
      families with an early-onset, recessive muscle and cardiac disorder. METHODS:
      Clinical and myopathological reevaluation of the five affected children,
      positional cloning, immunofluorescence, and Western blot studies were performed.
      RESULTS: All children presented with congenital muscle weakness and childhood
      onset fatal dilated cardiomyopathy. Skeletal muscle biopsies showed minicores,
      centrally located nuclei, and/or dystrophic lesions. In each family, we
      identified a homozygous titin deletion in exons encoding the C-terminal M-line
      region. Both deletions cause a frameshift downstream of the titin kinase domain
      and protein truncation. Immunofluorescence confirmed that truncated titins
      lacking the C-terminal end were incorporated into sarcomeres. Calpain 3 was
      secondarily depleted. INTERPRETATION: M-line titin homozygous truncations cause
      the first congenital and purely recessive titinopathy, and the first to involve
      both cardiac and skeletal muscle. These results expand the spectrum of early
      onset myopathies and suggest that titin segments downstream of the kinase domain
      are dispensable for skeletal and cardiac muscle development, but are crucial for
      maintaining sarcomere integrity.

PMID- 17444507
TI  - Fetal brain magnetic resonance imaging response acutely to hypoxia-ischemia
      predicts postnatal outcome.
AB  - OBJECTIVE: Cerebral palsy (CP) is caused by either hypoxia-ischemia (H-I) or long
      standing causative factors such as inflammation or genetics. Multiple
      pathophysiological events over time are thought to contribute eventually to
      cerebral palsy. Our objective was to examine whether the immediate response of
      the fetus to an acute H-I event determined the motor deficits associated with
      cerebral palsy. METHODS: Serial diffusion-weighted imaging were performed on 79%
      gestation New Zealand white rabbits using a 3-Tesla magnetic resonance scanner
      during 40 minutes of uterine ischemia, 20 minutes of reperfusion, and at 4, 24,
      and 72 hours. Individual fetuses were tracked to near term, and the delivered
      kits were divided into hypertonic H-I (n = 18), nonhypertonic H-I (n = 9),
      stillbirth H-I (n = 4), and control groups (n = 16). RESULTS: The hypertonia
      group had significantly less of a nadir in apparent diffusion coefficient (ADC)
      during H-I (71.6 +/- 23.8% vs 84.5 +/- 9.3% baseline) and slower and incomplete
      recovery of ADC during reperfusion compared with the nonhypertonic group. All
      fetuses in the hypertonic and stillbirth groups had an ADC nadir of less than
      0.83 microm(2)/msec (70.3% decrease from baseline), whereas 94% of control
      animals had an ADC nadir greater than this value. The difference between outcome
      groups was the largest at 4 hours reperfusion and persisted for 24 hours.
      INTERPRETATION: Serial fetal brain scans indicate that the immediate response of
      a fetus to H-I is crucial to the development of hypertonia. If the fetal brain
      can be scanned at the time of insult, ADC changes can predict which fetuses will
      have an unfavorable outcome.

PMID- 17444508
TI  - Mitochondrial coupling defect in Charcot-Marie-Tooth type 2A disease.
AB  - OBJECTIVE: Mutations of the mitofusin 2 gene (MFN2) may account for at least a
      third of the cases of Charcot-Marie-Tooth disease type 2 (CMT2). This study
      investigates mitochondrial cellular bioenergetics in MFN2-related CMT2A. METHODS:
      Mitochondrial network morphology and metabolism were studied in cultures of skin
      fibroblasts obtained from four CMT2A patients harboring novel missense mutations
      of the MFN2 gene. RESULTS: Although the mitochondrial network appeared
      morphologically unaltered, there was a significant defect of mitochondrial
      coupling associated with a reduction of the mitochondrial membrane potential.
      INTERPRETATION: Our results suggest that the sharply reduced efficacy of
      oxidative phosphorylation in MFN2-related CMT2A may contribute to the
      pathophysiology of the axonal neuropathy.

PMID- 17444509
TI  - Biomechanical comparison of a novel multilevel hex-head pedicle screw design with
      a conventional head design.
AB  - The objective of the study was to determine the biomechanical effect during
      insertion of multilevel hex-head design pedicle screws compared to a conventional
      screw-head design. Eighteen lumbar vertebrae and thoracic vertebrae from human
      cadavers were instrumented with a novel, multilevel hexagonal head pedicle screw
      on one side and a conventional head pedicle screw on the contralateral side.
      Screws were inserted at a constant rate and insertion and removal torques were
      recorded. A further 14 lumbar and thoracic vertebrae were used to test
      alterability of screw direction and operational effort required. Electromagnetic
      sensors recorded the change in angular direction for both screw and screwdriver.
      The force applied through the insertion screwdriver required to produce the
      directional change was also recorded. No significant differences were found
      between the two screw types for insertion or removal torque in either lumbar or
      thoracic vertebrae. Multilevel hex-head screws had significantly greater
      directional alterability than conventional head screws in both lumbar and
      thoracic specimens. Multilevel hex-head screws also required less force applied
      through the screwdriver than conventional screws to alter direction of screw
      insertion in both lumbar and thoracic specimens. The multilevel hex-head design
      did not affect the insertion or removal torque in comparison to a conventional
      head design.

PMID- 17444510
TI  - Age-related changes in reading systems of dyslexic children.
AB  - OBJECTIVE: To examine age-related changes in the neural systems for reading in
      nonimpaired and dyslexic children and adolescents. METHODS: Functional magnetic
      resonance imaging was used to study age-related changes in the neural systems for
      reading in a cross-sectional sample of 232 right-handed children 7 to 18 years of
      age (113 dyslexic readers and 119 nonimpaired readers) as they read pseudowords.
      RESULTS: In nonimpaired readers, systems in the left anterior lateral
      occipitotemporal area developed with age, whereas systems in the right superior
      and middle frontal regions decreased. In contrast, in dyslexic readers, systems
      in the left posterior medial occipitotemporal regions developed with age. Older
      nonimpaired readers were left lateralized in the anterior lateral
      occipitotemporal area; there was no difference in asymmetry between younger and
      older dyslexic readers. INTERPRETATION: These findings offer a possible
      neurobiological explanation for the differences in reading acquisition between
      dyslexic and nonimpaired readers and provide further evidence of the critical
      role of the left occipitotemporal region in the development of reading.

PMID- 17444512
TI  - Early editorial manuscript screening versus obligate peer review: a randomized
      trial.
AB  - Peer review is a cornerstone of scientific publication. However, it is time
      consuming for reviewers and contributors, and must be balanced with editorial
      oversight for balance and bias. To test a more efficient method of reviewing
      manuscripts, we performed a randomized trial comparing traditional peer review
      for all manuscripts received by the Annals of Neurology with an early screening
      approach in which six editors rejected a manuscript without external review when
      the chance of acceptance was deemed very low. Of the 351 manuscripts entered into
      the trial, 88 were randomized to traditional external review and 263 to early
      screening. Rates of final acceptance were similar in the two groups (p = 0.41).
      Final decisions were more delayed for traditional review (mean 48 days versus 18
      days with early screening; p < 0.0001) and more reviewers were required for each
      manuscript (mean 2.3 versus 0.7 with early screening; p < 0.0001). Among accepted
      manuscripts, reviewer ratings of scientific and clinical impact were similar. We
      conclude that a method of early screening of manuscripts for appropriateness for
      publication results in substantial decreases in the time between manuscript
      submission and publication decisions, and reduces the burden on reviewers with
      minimal impact on the quality of accepted manuscripts. Editorial screening is now
      journal policy.

PMID- 17444513
TI  - Newborn brain injury: looking back to the fetus.

PMID- 17444514
TI  - Genetic epidemiological studies of congenital/prelingual deafness in Turkey:
      population structure and mating type are major determinants of mutation
      identification.
AB  - In order to evaluate the genetic epidemiology of deafness in Turkey, we first
      analyzed the pedigree data obtained from 2,169 families whose children were
      students of the schools for hearing loss/deafness in 31 cities of Turkey. Single
      major locus segregation analysis was performed after families were grouped
      according to hearing status of the parents. The results showed that sporadic
      phenocopies, autosomal dominant, and autosomal recessive transmission account for
      18.2%, 4.9%, and 76.9% of the cases respectively, after exclusion of probands
      with unequivocal evidence for environmental etiologies. The high frequency of
      autosomal recessive transmission of this study differs from those of previous
      ones in Western populations. We subsequently analyzed the data from a subset of
      574 unrelated families that were evaluated clinically, including mutation
      analysis of the GJB2 gene in 406 probands. Biallelic mutations were detected in
      22.4% of all probands. They were present in 68.8% of probands whose parents were
      both deaf, yet in only 9.3% when both parents were hearing and consanguineous
      without a family history of deafness. Our study shows that GJB2 is the major gene
      for deafness in Turkey and was amplified in deaf by deaf matings, since
      assortative mating preferentially affects common genes. Deafness in the remaining
      families appears to result from mutations at many loci that are less frequent
      causes of deafness, because consanguinity has a proportionally greater effect on
      rare genes. Conclusions of this study may be relevant to other populations where
      consanguineous or assortative mating is present with various frequencies.

PMID- 17444515
TI  - A 1.55 A resolution X-ray crystal structure of HEF2/ERH and insights into its
      transcriptional and cell-cycle interaction networks.
AB  - Functional complementation screens can identify known or novel proteins with
      important intracellular activities. We have isolated human enhancer of
      filamentation 2 (HEF2) in a screen to find human genes that promote pseudohyphal
      growth in budding yeast. HEF2 is identical to enhancer of rudimentary homolog
      (ERH), a highly conserved protein of 104 amino acids. In silico protein
      interaction mapping implies that HEF2/ERH interacts with transcription factors,
      cell-cycle regulators, and other proteins shown to enhance filamentous growth in
      S. cerevisiae, suggesting a context for studies of HEF2/ERH function. To provide
      a mechanistic basis to study of HEF2/ERH, we have determined the crystal
      structure of HEF2/ERH at 1.55 A. The crystal asymmetric unit contains a HEF2/ERH
      monomer. The two monomers of the physiological dimer are related by the y, x, -z
      crystal symmetric operation. The HEF2/ERH structure is characterized by a novel
      alpha + beta fold, a four-strand antiparallel beta-sheet with three alpha-helixes
      on one side of the sheet. The beta-sheets from the two monomers together
      constitute a pseudo-beta-barrel, and form the center of the functional HEF2/ERH
      dimer, with a cavity channel at the dimer interface. Docking of this structure to
      the HEF2/ERH partner protein DCOH/PCD suggests that HEF2/ERH may regulate the
      oligomeric state of this protein. These data suggest that HEF2/ERH may be an
      important transcription regulator that also functions in the control of cell
      cycle progression.

PMID- 17444516
TI  - Protein docking using surface matching and supervised machine learning.
AB  - Computational prediction of protein complex structures through docking offers a
      means to gain a mechanistic understanding of protein interactions that mediate
      biological processes. This is particularly important as the number of
      experimentally determined structures of isolated proteins exceeds the number of
      structures of complexes. A comprehensive docking procedure is described in which
      efficient sampling of conformations is achieved by matching surface normal
      vectors, fast filtering for shape complementarity, clustering by RMSD, and
      scoring the docked conformations using a supervised machine learning approach.
      Contacting residue pair frequencies, residue propensities, evolutionary
      conservation, and shape complementarity score for each docking conformation are
      used as input data to a Random Forest classifier. The performance of the Random
      Forest approach for selecting correctly docked conformations was assessed by
      cross-validation using a nonredundant benchmark set of X-ray structures for 93
      heterodimer and 733 homodimer complexes. The single highest rank docking solution
      was the correct (near-native) structure for slightly more than one third of the
      complexes. Furthermore, the fraction of highly ranked correct structures was
      significantly higher than the overall fraction of correct structures, for almost
      all complexes. A detailed analysis of the difficult to predict complexes revealed
      that the majority of the homodimer cases were explained by incorrect oligomeric
      state annotation. Evolutionary conservation and shape complementarity score as
      well as both underrepresented and overrepresented residue types and residue pairs
      were found to make the largest contributions to the overall prediction accuracy.
      Finally, the method was also applied to docking unbound subunit structures from a
      previously published benchmark set.

PMID- 17444517
TI  - Computational approach to site-directed ligand discovery.
AB  - A computational approach, Systematic Conformational Search & Induced Fit
      (SCI&FI), to site-directed ligand discovery (Tethering) is presented. SCI&FI has
      the ability to predict the binding site, binding mode, and bound dynamics of
      small molecule fragments covalently tethered to a protein. The SCI&FI method was
      engineered with the ability to model induced fit conformational changes of the
      protein because of the binding of the tether. SCI&FI generates comprehensive
      picture of the binding preferences of the tether to the protein by elucidating
      potential binding sites of the tether and by describing regions of receptor space
      capable of conformational change because of the binding of the tether. The SCI&FI
      method provides a complementary approach to experimental tethering. Initial
      validation of the SCI&FI method is reported by predicting the 3D structure of two
      Interleukin-2 and an Interleukin-4 tethered-protein systems.

PMID- 17444518
TI  - Structure networks of E. coli glutaminyl-tRNA synthetase: effects of ligand
      binding.
AB  - It is well known that proteins undergo backbone as well as side chain
      conformational changes upon ligand binding, which is not necessarily confined to
      the active site. Both the local and the global conformational changes brought out
      by ligand-binding have been extensively studied earlier. However, the global
      changes have been reported mainly at the protein backbone level. Here we present
      a method that explicitly takes into account the side chain interactions, yet
      providing a global view of the ligand-induced conformational changes. This is
      achieved through the analysis of Protein Structure Networks (PSN), constructed
      from the noncovalent side chain interactions in the protein. Here, E. coli
      Glutaminyl-tRNA synthetase (GlnRS) in the ligand-free and different ligand-bound
      states is used as a case study to assess the effect of binding of tRNA, ATP, and
      the amino acid Gln to GlnRS. The PSNs are constructed on the basis of the
      strength of noncovalent interactions existing between the side chains of amino
      acids. The parameters like the size of the largest cluster, edge to node ratio,
      and the total number of hubs are used to quantitatively assess the structure
      network changes. These network parameters have effectively captured the ligand
      induced structural changes at a global structure network level. Hubs, the highly
      connected amino acids, are also identified from these networks. Specifically, we
      are able to characterize different types of hubs based on the comparison of
      structure networks of the GlnRS system. The differences in the structure networks
      in both the presence and the absence of the ligands are reflected in these hubs.
      For instance, the characterization of hubs that are present in both the ligand
      free and all the ligand-bound GlnRS (the invariant hubs) might implicate their
      role in structural integrity. On the other hand, identification of hubs unique to
      a particular ligand-bound structure (the exclusive hubs) not only highlights the
      structural differences mediated by ligand-binding at the structure network level,
      but also highlights significance of these amino acids hubs in binding to the
      ligand and catalyzing the biochemical function. Further, the hubs identified from
      this study could be ideal targets for mutational studies to ascertain the ligand
      induced structure-function relationships in E. coli GlnRS. The formalism used in
      this study is simple and can be applied to other protein-ligands in general to
      understand the allosteric changes mediated by the binding of ligands.

PMID- 17444519
TI  - pyDock: electrostatics and desolvation for effective scoring of rigid-body
      protein-protein docking.
AB  - The accurate scoring of rigid-body docking orientations represents one of the
      major difficulties in protein-protein docking prediction. Other challenges are
      the development of faster and more efficient sampling methods and the
      introduction of receptor and ligand flexibility during simulations. Overall, good
      discrimination of near-native docking poses from the very early stages of rigid
      body protein docking is essential step before applying more costly interface
      refinement to the correct docking solutions. Here we explore a simple approach to
      scoring of rigid-body docking poses, which has been implemented in a program
      called pyDock. The scheme is based on Coulombic electrostatics with distance
      dependent dielectric constant, and implicit desolvation energy with atomic
      solvation parameters previously adjusted for rigid-body protein-protein docking.
      This scoring function is not highly dependent on specific geometry of the docking
      poses and therefore can be used in rigid-body docking sets generated by a variety
      of methods. We have tested the procedure in a large benchmark set of 80 unbound
      docking cases. The method is able to detect a near-native solution from 12,000
      docking poses and place it within the 100 lowest-energy docking solutions in 56%
      of the cases, in a completely unrestricted manner and without any other
      additional information. More specifically, a near-native solution will lie within
      the top 20 solutions in 37% of the cases. The simplicity of the approach allows
      for a better understanding of the physical principles behind protein-protein
      association, and provides a fast tool for the evaluation of large sets of rigid
      body docking poses in search of the near-native orientation.

PMID- 17444520
TI  - Structure-based protein engineering for alpha-amylase inhibitory activity of
      plant defensin.
AB  - The structure of a novel plant defensin isolated from the seeds of the mung bean,
      Vigna radiate, has been determined by (1)H nuclear magnetic resonance
      spectroscopy. The three-dimensional structure of VrD2, the V. radiate plant
      defensin 2 protein, comprises an alpha-helix and one triple-stranded anti
      parallel beta-sheet stabilized by four disulfide bonds. This protein exhibits
      neither insecticidal activity nor alpha-amylase inhibitory activity in spite of
      showing a similar global fold to that of VrD1, an insecticidal plant defensin
      that has been suggested to function by inhibiting insect alpha-amylase. Our
      previous study proposed that loop L3 of plant defensins is important for this
      inhibition. Structural analyses and surface charge comparisons of VrD1 and VrD2
      revealed that the charged residues of L3 correlate with the observed difference
      in inhibitory activities of these proteins. A VrD2 chimera that was produced by
      transferring the proposed functional loop of VrD1 onto the structurally
      equivalent loop of VrD2 supported this hypothesis. The VrD2 chimera, which
      differs by only five residues compared with VrD2, showed obvious activity against
      Tenebrio molitor alpha-amylase. These results clarify the mode of alpha-amylase
      inhibition of plant defensins and also represent a possible approach for
      engineering novel alpha-amylase inhibitors. Plant defensins are important
      constituents of the innate immune system of plants, and thus the application of
      protein engineering to this protein family may provide an efficient method for
      protecting against crop losses.

PMID- 17444521
TI  - Drug block of the hERG potassium channel: insight from modeling.
AB  - Many commonly used, structurally diverse, drugs block the human ether-a-go-go
      related gene (hERG) K(+) channel to cause acquired long QT syndrome, which can
      lead to sudden death via lethal cardiac arrhythmias. This undesirable side effect
      is a major hurdle in the development of safe drugs. To gain insight about the
      structure of hERG and the nature of drug block we have produced structural models
      of the channel pore domain, into each of which we have docked a set of 20 hERG
      blockers. In the absence of an experimentally determined three-dimensional
      structure of hERG, each of the models was validated against site-directed
      mutagenesis data. First, hERG models were produced of the open and closed channel
      states, based on homology with the prokaryotic K(+) channel crystal structures.
      The modeled complexes were in partial agreement with the mutagenesis data. To
      improve agreement with mutagenesis data, a KcsA-based model was refined by
      rotating the four copies of the S6 transmembrane helix half a residue position
      toward the C-terminus, so as to place all residues known to be involved in drug
      binding in positions lining the central cavity. This model produces complexes
      that are consistent with mutagenesis data for smaller, but not larger, ligands.
      Larger ligands could be accommodated following refinement of this model by
      enlarging the cavity using the inherent flexibility about the glycine hinge
      (Gly648) in S6, to produce results consistent with the experimental data for the
      majority of ligands tested.

PMID- 17444522
TI  - Detection of pockets on protein surfaces using small and large probe spheres to
      find putative ligand binding sites.
AB  - One of the simplest ways to predict ligand binding sites is to identify pocket
      shaped regions on the protein surface. Many programs have already been proposed
      to identify these pocket regions. Examination of their algorithms revealed that a
      pocket intrinsically has two arbitrary properties, "size" and "depth". We
      proposed a new definition for pockets using two explicit adjustable parameters
      that correspond to these two arbitrary properties. A pocket region is defined as
      a space into which a small probe can enter, but a large probe cannot. The radii
      of small and large probe spheres are the two parameters that correspond to the
      "size" and "depth" of the pockets, respectively. These values can be adjusted
      individual putative ligand molecule. To determine the optimal value of the large
      probe spheres radius, we generated pockets for thousands of protein structures in
      the database, using several size of large probe spheres, examined the
      correspondence of these pockets with known binding site positions. A new measure
      of shallowness, a minimum inaccessible radius, R(inaccess), indicated that
      binding sites of coenzymes are very deep, while those for adenine/guanine
      mononucleotide have only medium shallowness and those for short peptides and
      oligosaccharides are shallow. The optimal radius of large probe spheres was 3-4 A
      for the coenzymes, 4 A for adenine/guanine mononucleotides, and 5 A or more for
      peptides/oligosaccharides. Comparison of our program with two other popular
      pocket-finding programs showed that our program had a higher performance of
      detecting binding pockets, although it required more computational time.

PMID- 17444524
TI  - Benchmarking of TASSER in the ab initio limit.
AB  - A significant number of protein sequences in a given proteome have no obvious
      evolutionarily related protein in the database of solved protein structures, the
      PDB. Under these conditions, ab initio or template-free modeling methods are the
      sole means of predicting protein structure. To assess its expected performance on
      proteomes, the TASSER structure prediction algorithm is benchmarked in the ab
      initio limit on a representative set of 1129 nonhomologous sequences ranging from
      40 to 200 residues that cover the PDB at 30% sequence identity and which adopt
      alpha, alpha + beta, and beta secondary structures. For sequences in the 40-100
      (100-200) residue range, as assessed by their root mean square deviation from
      native, RMSD, the best of the top five ranked models of TASSER has a global fold
      that is significantly close to the native structure for 25% (16%) of the
      sequences, and with a correct identification of the structure of the protein core
      for 59% (36%). In the absence of a native structure, the structural similarity
      among the top five ranked models is a moderately reliable predictor of folding
      accuracy. If we classify the sequences according to their secondary structure
      content, then 64% (36%) of alpha, 43% (24%) of alpha + beta, and 20% (12%) of
      beta sequences in the 40-100 (100-200) residue range have a significant TM-score
      (TM-score > or = 0.4). TASSER performs best on helical proteins because there are
      less secondary structural elements to arrange in a helical protein than in a beta
      protein of equal length, since the average length of a helix is longer than that
      of a strand. In addition, helical proteins have shorter loops and dangling tails.
      If we exclude these flexible fragments, then TASSER has similar accuracy for
      sequences containing the same number of secondary structural elements,
      irrespective of whether they are helices and/or strands. Thus, it is the
      effective configurational entropy of the protein that dictates the average
      likelihood of correctly arranging the secondary structure elements.

PMID- 17444523
TI  - Crystal structure of TM1030 from Thermotoga maritima at 2.3 A resolution reveals
      molecular details of its transcription repressor function.

PMID- 17444525
TI  - The importance of narcissism in predicting proactive and reactive aggression in
      moderately to highly aggressive children.
AB  - The present study examined the importance of psychopathy-linked narcissism in
      predicting proactive and reactive aggression and conduct problems in a group of
      160 moderately to highly aggressive children (mean age of 10 years, 9 months).
      Children's self-report of self-esteem and parent and teacher report of dimensions
      of psychopathy [narcissism, callous-unemotional (CU) traits, and impulsivity],
      proactive and reactive aggression, and conduct problems were collected.
      Composites of parent and teacher ratings of children's behavior were used.
      Consistent with the study's hypotheses, narcissism predicted unique variance in
      both proactive and reactive aggression, even when controlling for other
      dimensions of psychopathy, demographic variables associated with narcissism, and
      the alternative subtype of aggression. As hypothesized, impulsivity was
      significantly associated with only reactive aggression. CU traits were not
      related to proactive or reactive aggression once the control variables were
      entered. All dimensions of psychopathy predicted unique variance in conduct
      problems. Consistent with prediction, narcissism was not significantly related to
      general self-esteem, providing support that narcissism and self-esteem are
      different constructs. Furthermore, narcissism and self-esteem related
      differentially to proactive aggression, reactive aggression, and conduct
      problems. Furthermore, narcissism but not self-esteem accounted for unique
      variance in aggression and conduct problems. The importance of narcissism in the
      prediction of aggressive behaviors and clinical implications are discussed.

PMID- 17444526
TI  - Reactive, but not proactive aggression predicts victimization among boys.
AB  - Prospective links among reactive aggression, proactive aggression, and
      victimization by peers were investigated in a longitudinal sample of 238
      preadolescents (aged 10-13 years, 52% girls). No predictive links were found
      between victimization and either type of aggression among girls. Among boys,
      reactive aggression predicted higher future levels of victimization but was not
      itself affected by prior victimization. In contrast, boys' proactive aggression
      predicted lower levels of future victimization and was itself reduced by their
      prior victimization. Finally, reactive aggression predicted later proactive
      aggression for both boys and girls. These results are explained in terms of the
      different reactions that others have to proactive and reactive aggression, the
      different functions they serve, and to the different types of aggression that are
      common for boys and girls.

PMID- 17444527
TI  - Impact of neighborhood disadvantage on overt behavior problems during early
      childhood.
AB  - Researchers have yet to examine the impact of neighborhood disadvantage on early
      child behavior problems (BPs) longitudinally. We examined the impact of
      neighborhood disadvantage on overt BPs in a low-income, urban sample of 281
      African American and European American boys followed longitudinally from
      toddlerhood to school entry. Measures included census data and maternal report of
      BPs, sociocultural factors, parental criminality, and maternal depressive
      symptomatology. After controlling for age 2 overt BPs, family selection
      variables, and residential instability, neighborhood effects on boys' behavior
      emerged, but only at age 6 and only at the extreme of neighborhood disadvantage
      (i.e., underclass). Findings suggest boys in underclass neighborhoods are at risk
      for overt BPs as they make the transition to elementary school.

PMID- 17444528
TI  - Characteristics of male and female prisoners involved in bullying behavior.
AB  - This study explores bullying behavior in a larger and more representative sample
      than previous prison-based research. It has two core aims, first to explore the
      nature of bullying in relation to indirect and direct aggression and, second, to
      explore the predictors of bully-category membership with particular reference to
      behavioral characteristics. Participants were adult men (n=728) and women (n=525)
      prisoners. All completed a behavioral measure of behavior indicative of bullying
      (Direct and Indirect Prisoner behavior Checklist, DIPC) that also explored prison
      based behavior such as negative acts towards staff or prison rules, positive acts
      and drug-related behavior. Indirect aggression was, as predicted, reported more
      frequently than direct aggression, although this only held for perpetration.
      Bully-victims, as predicted, showed more negative behavior. Pure bullies and pure
      victims also showed more negative behavior than the other categories. The
      findings are discussed in relation to the environment in which bullying behavior
      is being assessed and with attention to the possible motivations underlying both
      bullying and negative behavior. Directions for future research are suggested.

PMID- 17444529
TI  - Relation between childhood peer victimization and adult perfectionism: are
      victims of indirect aggression more perfectionistic?
AB  - Using two independent samples and two different measures of perfectionism, this
      study investigated the hypothesized relation between retrospective accounts of
      perceived peer-inflicted emotional abuse during childhood and perfectionism in
      adulthood. Emotional victimization ('indirect' aggression) is characterized by
      behavior in which mental harm is inflicted on victims through exclusionary acts,
      gossiping, and rumor spreading. Study one: Self-reported questionnaires of
      indirect victimization [DIAS; Bjorkqvist, Lagerspetz, and Osterman, 1992] and
      perfectionism [multidimensional perfectionism scale; Hewitt and Flett, 1991] were
      administered to 162 (mean age=20.14 years) female undergraduate psychology
      students. Results support the predicted positive relationship between recalled
      indirect peer victimization and current socially prescribed/self-oriented
      perfectionism. Study two: self-reports of indirect peer victimization and
      perfectionism (eating disorder inventory-perfectionism) were collected from 196
      (mean age=19.5 years) female undergraduate students. Again, recalled indirect
      peer victimization was a statistically significant predictor of current socially
      prescribed/self-oriented perfectionism whereas recalled direct (physical, verbal)
      peer victimization held no relation. Discussion addresses the implications of
      these results, which hold importance for both the bullying and perfectionism
      literatures.

PMID- 17444530
TI  - Adolescent psychopathy features: 6-year temporal stability and the prediction of
      externalizing symptoms during the transition to adulthood.
AB  - This study investigated the 6-year stability and predictive validity of
      adolescent psychopathy features during the transition to young adulthood. It
      represents one of the longest outcome studies of youth psychopathy to date, and
      therefore addresses a primary criticism of the research area (i.e., lack of
      demonstrated associations between child and adult psychopathy features).
      Recruited participants were 475 males enrolled in the Minnesota Twin and Family
      Study who had completed a research-based measure of psychopathy features
      consisting of separate emotional detachment (or affective) and antisocial
      tendencies (or behavioral) subscales. These psychopathy features and various
      externalizing symptoms (i.e., conduct problems, impulsivity, and substance use
      disorder) were assessed through rating scales and structured diagnostic interview
      at an intake assessment (ages 16-18) and 6-year follow-up. Consistent with
      prediction, adolescent psychopathy features displayed moderate stability across
      the transition from adolescence to adulthood [intraclass correlation coefficients
      (ICCs) = 0.40-0.41]. The antisocial tendencies subscale was uniquely related to
      most externalizing symptoms both in adolescence and in adulthood, whereas the
      emotional detachment subscale showed appropriate discriminant validity in its
      lack of association with externalizing symptoms. These findings suggest that
      psychopathy features are relatively stable from adolescence to adulthood and
      provide possible insights into the development and maintenance of externalizing
      difficulties during the adult transition.

PMID- 17444531
TI  - Domestic violence and psychopathic traits: distinguishing the antisocial batterer
      from other antisocial offenders.
AB  - The proliferation of specialized domestic batterer treatment programs suggests
      that batterers differ from other offenders in important ways. The psychopathic
      personality represents a constellation of personality traits, which may be
      relevant to the differentiation of batterers from other offenders. In a sample of
      172 county jail inmates, we examined whether antisocial batterers can be
      distinguished from the larger pool of antisocial offenders on the basis of the
      four-facet model of psychopathy identified for the Psychopathy Checklist-Revised
      (PCL-R). Batterer/non-batterer status was positively related to the PCL-R
      affective facet and negatively related to the lifestyle facet, but there was no
      significant relationship between PCL-R total scores and this criterion. Results
      suggest that antisocial batterers are characterized by deficient affective
      experience and by reduced impulsivity and irresponsibility compared with other
      antisocial offenders. Implications are discussed in light of specialized
      treatments for batterers.

PMID- 17444532
TI  - Gender differences in emotional and overt/covert aggressive responses to stress.
AB  - We examined the role of stress exposure on gender differences in hostile
      (emotional and behavioral) reactions within the context of a laboratory paradigm.
      Aggressive behavior was indexed via the intensity (overt) and the duration
      (covert) of putative shocks delivered to a confederate. Half of the participants
      were exposed to a chronic stressor (high stress) and half were not (low stress).
      Participants' emotional responses were measured via self-report mood ratings
      before and after the experiment. Men displayed higher aggression in both stress
      conditions, which corresponded to their ratings of state hostility. On the other
      hand, women in high stress delivered lower intensity shocks, and this decreased
      overt aggression was positively correlated with sadness ratings. However, women
      did not decrease their levels of shock duration (covert aggression) under high
      stress and showed equivalent shock duration compared with men in high stress.
      These findings are discussed in terms of differential overt manifestations of
      distress between men and women.

PMID- 17444533
TI  - Unemployment and civil commitment: a test of the intolerance hypothesis.
AB  - We theorize that the reported association between economic indicators and the
      incidence of civil commitment for mental illness may result, at least in part,
      from reduced tolerance in the community for impaired behavior among minorities.
      Earlier work suggests that economically induced intolerance will be focused
      primarily on minority males. Based on this literature, we hypothesize that the
      median level of functioning among African-American males subjected to civil
      commitment will vary positively with earlier changes in the unemployment rate.
      The test applies Box-Jenkins methods to 156 months (August 1985-July 1998) of
      data from California. Consistent with theory, results support the hypothesis.

PMID- 17444534
TI  - The syndrome of transient epileptic amnesia.
AB  - OBJECTIVE: Transient amnesia can be the principal manifestation of epilepsy. This
      diagnosis, however, is seldom suspected by clinicians and remains controversial.
      The amnestic attacks are often associated with persistent memory complaints. This
      study was designed to provide the first description of transient epileptic
      amnesia in a substantial series of patients. METHODS: Fifty patients were
      recruited over 18 months using the following diagnostic criteria: (1) recurrent,
      witnessed episodes of amnesia; (2) other cognitive functions intact during
      attacks; and (3) compelling evidence of epilepsy. We assessed clinical features
      and performed neuropsychological evaluation in cases and 24 matched control
      subjects. RESULTS: Transient epileptic amnesia develops in later life (mean
      onset, 62 years). Amnestic episodes are frequent (median, 12/year), brief (median
      duration, 30-60 minutes), and often occur on waking (37/50 cases). Epilepsy was
      the initial specialist diagnosis in only 12 of 50 cases. Attacks ceased on
      anticonvulsant medication in 44 of 47 treated patients. A total of 40 of 50 cases
      described persistent memory difficulties. Despite normal performance on standard
      memory tests, patients exhibited accelerated forgetting of verbal and visual
      material over 3 weeks by comparison with matched control subjects (p < 0.001).
      They also showed loss of autobiographical memories for events extending back over
      40 years (p < 0.05). INTERPRETATION: We propose that transient epileptic amnesia
      is a distinctive epilepsy syndrome, typically misdiagnosed at presentation and
      associated with accelerated long-term forgetting and autobiographical amnesia.
      The syndrome is of clinical and theoretic importance.

PMID- 17444535
TI  - Is hemiplegic cerebral palsy equivalent to amblyopia of the corticospinal system?
AB  - OBJECTIVE: Subjects with severe hemiplegic cerebral palsy have increased
      ipsilateral corticospinal projections from their noninfarcted cortex. We
      investigated whether their severe impairment might, in part, be caused by
      activity-dependent, competitive displacement of surviving contralateral
      corticospinal projections from the affected cortex by more active ipsilateral
      corticospinal projections from the nonaffected cortex, thereby compounding the
      impairment. METHODS: Transcranial magnetic stimulation (TMS) characterized
      corticospinal tract development from each hemisphere over the first 2 years in 32
      healthy children, 14 children with unilateral stroke, and 25 with bilateral
      lesions. Magnetic resonance imaging and anatomic studies compared corticospinal
      tract growth in 13 patients with perinatal stroke with 46 healthy subjects.
      RESULTS: Infants with unilateral lesions initially had responses after TMS of the
      affected cortex, which became progressively more abnormal, and seven were
      eventually lost. There was associated hypertrophy of the ipsilateral
      corticospinal axons projecting from the noninfarcted cortex. Magnetic resonance
      imaging and anatomic studies demonstrated hypertrophy of the corticospinal tract
      from the noninfarcted hemisphere. TMS findings soon after the stroke did not
      predict impairment; subsequent loss of responses and hypertrophy of ipsilateral
      corticospinal axons from the noninfarcted cortex predicted severe impairment at 2
      years. Infants with bilateral lesions maintained responses to TMS from both
      hemispheres with a normal pattern of development. INTERPRETATION: Rather than
      representing "reparative plasticity," increased ipsilateral projections from the
      noninfarcted cortex compound disability by competitively displacing surviving
      contralateral corticospinal projections from the infarcted cortex. This may
      provide a pathophysiological explanation for why signs of hemiplegic cerebral
      palsy appear late and progress over the first 2 years of life.

PMID- 17444536
TI  - Assessment of the third-trimester fetus using 3-dimensional volumes: a pilot
      study.
AB  - PURPOSE: To examine whether the third-trimester fetus can be assessed
      sonographically using 3-dimensional (3D) volume data sets. METHODS: Twenty-seven
      consecutive third-trimester fetuses were evaluated. Fetuses were scanned using 2
      dimensional (2D) imaging followed by 5 3D volume acquisitions. The initial scan
      was interpreted and reported based on the 2D images. The 3D volume data sets were
      independently reviewed offline several weeks later by 2 sonologists. Parameters
      evaluated included fetal presentation, placental location, amniotic fluid volume,
      fetal biometry including a calculation of estimated fetal weight, and major fetal
      anatomic structures. The result of the interpretation via 3D reconstruction of
      the volume from each of the 2 sonologists was compared with the original 2D
      sonography report. RESULTS: Fetal presentation, amniotic fluid volume, and
      placental location with respect to the cervix were correctly identified 100% of
      the time by each sonologist. The estimated fetal weight was within 10% of the 2D
      estimate 89% (95% CI, 0.71-0.98) of the time for sonologist A and 96% (95% CI,
      0.81-0.99) of the time for sonologist B. The majority of major anatomic landmarks
      were adequately seen by both sonologists. CONCLUSION: Offline review of 3D volume
      data sets is a reliable method for determining fetal presentation, amniotic fluid
      volume, placental location, and estimating fetal weight in the third trimester.

PMID- 17444537
TI  - De novo synthesis of uronic acid building blocks for assembly of heparin
      oligosaccharides.
AB  - An efficient de novo synthesis of uronic acid building blocks is described. The
      synthetic strategy relies on the stereoselective elongation of thioacetal
      protected dialdehydes 12 a and 17. The dialdehydes are prepared from D-xylose, a
      cheap and commercially available source. A highly stereoselective MgBr(2)OEt(2)
      mediated Mukaiyama aldol addition to C4-aldehyde 12 a is performed to obtain D
      glucuronic acid building block 16, whereas L-iduronic acid building block 22 is
      prepared by MgBr(2)OEt(2)-mediated cyanation of C5-aldehyde 17. Synthesis of a
      heparin disaccharide demonstrates the utility of the de novo strategy for the
      assembly of glycosaminoglycan oligosaccharides.

PMID- 17444538
TI  - Photochemically initiated single polymer immobilization.
AB  - This Concept article surveys methods for attaching single polymer molecules on
      solid substrates. A general approach to single polymer immobilization based on
      the photochemistry of perfluorophenylazides is elaborated.

PMID- 17444539
TI  - In situ and operando spectroscopy for assessing mechanisms of gas sensing.
AB  - The mechanistic description of gas sensing on inorganic, organic, and polymeric
      materials is of great scientific and technological interest. The understanding of
      surface and bulk reactions responsible for gas-sensing effects will lead to
      increased selectivity and sensitivity in the chemical determination of gases and
      thus to the development of better sensors. In recent years, spectroscopic tools
      have been developed to follow the physicochemical processes taking place in an
      active sensing element in real time and under operating conditions. Thus, the
      monitoring of the processes in "living" gas sensors is no longer an unsolvable
      problem. This Review gives an overview of in situ and operando spectroscopic
      techniques for the study of gas-sensing mechanisms on solid-state sensors.

PMID- 17444540
TI  - Deprotonative metalation using ate compounds: synergy, synthesis, and structure
      building.
AB  - Historically, single-metal organometallic species such as organolithium compounds
      have been the reagents of choice in synthetic organic chemistry for performing
      deprotonation reactions. Over the past few years, a complementary new class of
      metalating agents has started to emerge. Owing to a variable central metal
      (magnesium, zinc, or aluminum), variable ligands (both in their nature and
      number), and a variable second metallic center (an alkali metal such as lithium
      or sodium), "ate" complexes are highly versatile bases that exhibit a synergic
      chemistry which cannot be replicated by the homometallic magnesium, zinc, or
      aluminum compounds on their own. Deprotonation accomplished by using these
      organometallic ate complexes has opened up new perspectives in organic chemistry
      with unprecedented reactivities and sometimes unusual and unpredictable
      regioselectivities.

PMID- 17444541
TI  - Generation of live-cell microarrays by means of DNA-Directed immobilization of
      specific cell-surface ligands.

PMID- 17444542
TI  - Synthesis of pentaantennary N-glycans with bisecting GlcNAc and core fucose.

PMID- 17444543
TI  - Carbanions with two N substituents: nucleophilic acyl-group-transfer reagents.

PMID- 17444544
TI  - Application of AXAFS spectroscopy to transition-metal oxides: influence of the
      nearest and next nearest neighbour shells in vanadium oxides.
AB  - The influence of changes in coordination number, interatomic distances, and
      oxidation state on the intensity and centroid position of the Fourier transform
      (FT) of the atomic X-ray absorption fine structure (AXAFS) peak of vanadium oxide
      bulk model compounds and alumina-supported vanadium oxide clusters has been
      investigated. Using Na3VO4 and V2O5 as model compounds, it has been shown that
      the nearest neighbour shells have a pronounced influence on the AXAFS intensity;
      specifically, a 40 % decrease in intensity was observed between these two
      compounds. Secondly, the influence of partial reduction of the vanadium oxide
      species has been determined; this led to a 50 % decrease in the AXAFS intensity
      and to an increase in the centroid position. Furthermore, the influence of the
      vanadium oxide loading has been assessed. A non-linear relationship between the
      vanadium oxide loading and the AXAFS intensity has been found, indicating that
      the AXAFS intensity is sensitive to the formation of V-O-V bridging bonds between
      the vanadium VO4 clusters. The results show that AXAFS can be used to probe the
      relative energy level of the vanadium valence orbitals.

PMID- 17444545
TI  - Exhaustive analysis of frontal copolymerization of functionalized monovinyl and
      divinyl monomers.
AB  - A series of copolymers of 2-hydroxyethyl methacrylate (HEMA)/glycidyl
      methacrylate (GMA) and ethylene dimethacrylate (EGDM) were synthesized by frontal
      polymerization (FP). This study was conducted to investigate the effect of
      crosslink density, type and concentration of initiator, the use of a complex
      initiator system, porogen, and diluent on the most relevant parameters of FP,
      such as sustainability of the front, temperature profile, front velocity, and
      yield. The products were also characterized for intruded pore volume, pore-size
      distribution, epoxy-functionality number, and surface morphology. Higher
      crosslink densities (CLDs) and initiator concentration produced higher front
      velocities, whereas no trend in front temperature was noted. A complex initiation
      system was effective in stabilizing and increasing the polymerization yield.
      Relative to suspension polymerization (SP), FP products synthesized without a
      solvent were microporous, whereas micro-to-macroporous products were obtained in
      the presence of a solvent (for HEMA-EGDM polymers). We also present, explain, and
      discuss the exotic patterns observed under a microscope. We observed two basic
      types of spatial patterns, namely, planar and nonplanar patterns. The type of
      planar pattern observed under scanning electron microscopy (SEM) has a spatial
      impulse that appears as a loop followed by regular periodic motion in the radial
      and axial directions. This behavior gives rise to a repeating pattern that is a
      few microns thick. Also, nonplanar patterns, namely, layered concentric rings and
      winding staircase patterns, were observed under SEM.

PMID- 17444546
TI  - Synthesis of large ring macrocycles (12-18) by recyclable palladium-complexed
      dendrimers on silica gel catalyzed intramolecular cyclocarbonylation reactions.
AB  - Intramolecular cyclocarbonylation reactions with palladium-complexed dendrimers
      on silica gel as catalysts are very effective for the synthesis of twelve- to
      eighteen-membered ring macrocycles. This process can tolerate a wide variety of
      functional groups, including halide, ether, ketone, and ester. The heterogeneous
      dendritic catalysts facilitate excellent substrate reactivity, affording oxygen-,
      nitrogen-, or sulfur-containing tricyclic heterocycles in 70-92 % yields.
      Importantly, these systems are easily recovered by simple filtration and reused
      several times with only a slight loss of activity.

PMID- 17444547
TI  - [3.3]Ferrocenophanes with guanidine bridging units as multisignalling receptor
      molecules for selective recognition of anions, cations, and amino acids.
AB  - The synthesis, electrochemical, and optical properties of a new
      [3.3]ferrocenophane framework in which two ferrocene subunits, with similar
      electronic environments, are linked through two substituted guanidine moieties,
      are reported. The receptors 4-7 have been prepared in good yields by the reaction
      of bis(carbodiimide) 3 with primary amines. This architecture is exceptionally
      "tunable" because a variety of "legs" may be appended to the basic
      [3.3]ferrocenophane scaffold to give a wide range of signaling units. These
      receptors show remarkable ion-sensing properties, due to the presence of a redox
      active unit (ferrocene), and an amphoteric binding site (guanidine). In this
      nitrogen-rich structural motif the guanidine bridges act as multipoint binding
      sites for anions, cations, and amino acids. Sensing of anions takes place both by
      unprecedented redox-ratiometric measurements (F-, Cl-, AcO-, NO3-, HSO4-, H2PO4-,
      and HP2O7(3-)), and colorimetric change (F-, AcO-, H2PO4-, and HP2O7(3-)).
      Sensing and discrimination of amino acids takes place by redox-ratiometric
      measurements, whereas the recognition of metal cations (Zn2+, Ni2+, and Cd2+) is
      achieved either by electrochemical or fluorescence measurements. Moreover, the
      reported receptors display splitting of the oxidation wave of the Fe(II)/Fe(III)
      redox couple, and form the mixed-valence species 4+* -7+* by electrochemical
      partial oxidation which, interestingly, show intervalence charge-transfer
      transitions associated to the appearance of absorption bands in the near infrared
      spectral region.

PMID- 17444548
TI  - Heterogeneous Pd/C-catalyzed ligand-free, room-temperature Suzuki-Miyaura
      coupling reactions in aqueous media.
AB  - A mild and efficient ligand-free Suzuki-Miyaura coupling reaction catalyzed by
      heterogeneous Pd/C was developed. Aryl bromides and triflates undergo the cross
      coupling with aryl boronic acids in excellent yields without the presence of any
      additives in aqueous media at room temperature. Aryl vinyl boronic acids are also
      applicable to this coupling reaction and provide the trans-stilbene derivatives
      in high yields. The application of wet-type Pd/C to the coupling reaction was
      achieved without any loss of activity under aerobic conditions, and the reuse of
      Pd/C is feasible for a fifth run without significant loss of activity.
      Inductively coupled plasma (ICP) mass-spectrometric analysis of the filtrate from
      the reaction mixture of 4-bromonitrobenzene with phenylboronic acid demonstrated
      that the palladium metal hardly leached into the solution within the limits of
      the detector (<1 ppm), thus suggesting that the present Suzuki-Miyaura reaction
      proceeded by heterogeneous catalysis.

PMID- 17444549
TI  - The role of CnTI-SonoVue in the diagnosis of ovarian masses with papillary
      projections: a preliminary study.
AB  - OBJECTIVES: To describe sonographically the distribution patterns of a second
      generation contrast agent in the microcirculation of unilocular and multilocular
      ovarian masses with papillary projections, and to investigate whether qualitative
      evaluation of the passage of the contrast agent can improve the performance of
      sonography in distinguishing between benign and malignant masses with papillary
      projections. METHODS: Thirty-three patients with unilocular or multilocular
      ovarian masses with papillary projections were enrolled into the study in three
      clinical centers. The contrast-enhanced transvaginal examination was performed
      using 'Contrast Tuned Imaging' (CnTI) technology and SonoVue ultrasound contrast
      agent. RESULTS: Twenty-four (73%) lesions were benign, eight (24%) were
      borderline ovarian tumors, and one patient presented with an endometrioid ovarian
      adenocarcinoma. On color and power Doppler examinations the presence of vessels
      was demonstrated in 17 papillary projections, while on CnTI-SonoVue examination,
      the presence of vessels was shown in these 17 and in six additional cases. In all
      cases with absent papillary perfusion after SonoVue intravenous injection, the
      cyst wall appeared unequivocally regular. The sensitivity and specificity of
      conventional color Doppler examination with regard to malignancy were 100% and
      67% and the positive and negative likelihood ratios were 3.03 and 0.16,
      respectively. For the contrast-enhanced examination the corresponding values were
      100%, 42%, 1.7 and 0.26. The difference in specificity was statistically
      significant (P<0.05) because 14 cases, in which papillary perfusion was detected
      after SonoVue injection, proved to be benign on pathological examination.
      CONCLUSION: Qualitative evaluation of blood circulation in papillary projections
      using CnTI-SonoVue examination does not improve the discrimination of benign from
      borderline/malignant ovarian masses with papillary projections.

PMID- 17444550
TI  - Predicting preterm delivery in asymptomatic patients with prior preterm delivery
      by measurement of cervical length and phosphorylated insulin-like growth factor
      binding protein-1.
AB  - OBJECTIVE: To evaluate the efficacy of cervical length measurement in combination
      with a bedside assessment of phosphorylated insulin-like growth factor-binding
      protein-1 (phIGFBP-1) as a predictor of preterm delivery in asymptomatic pregnant
      women with a history of preterm birth. METHODS: Cervical length was measured
      using transvaginal sonography at 22-24 weeks of gestation in 105 singleton
      pregnancies and a rapid strip test was performed to detect phIGFBP-1 in cervical
      secretions from 24 to 34 weeks. Receiver-operating characteristics (ROC) curves
      were constructed to compare the performance of phIGFBP-1 at different gestational
      ages, and cervical length at 22-24 weeks, in predicting preterm delivery.
      RESULTS: The rate of spontaneous delivery before 37 and 34 weeks was 23.8% and
      11.4%, respectively. Women with cervical lengths less than 20 mm had a risk of
      spontaneous preterm delivery before 34 and 37 weeks of 43.5% and 69.6%,
      respectively. The performance of phIGFBP-1 levels as a predictor of preterm
      delivery was significantly higher when the test was carried out at 30 weeks'
      gestation. Cervical assessment in combination with phIGFBP-1 at 30 weeks had the
      steepest ROC curve (area under the curve=0.93; 95% CI, 0.88-0.98, P<0.001).
      CONCLUSION: Both cervical length and phIGFBP-1 measurement are useful in the
      prediction of preterm delivery in patients with a history of preterm birth and
      the combined method of measuring cervical length at 22-24 weeks and phIGFBP-1 at
      30 weeks improves upon either method used alone.

PMID- 17444551
TI  - Quantitative assessment of gestational sac shape: the gestational sac shape
      score.
AB  - OBJECTIVE: To develop a quantitative method for characterizing gestational sac
      shape. METHODS: Twenty first-trimester gestational sacs in normal pregnancies
      were studied with three-dimensional (3D) ultrasonography. The 3D coordinates of
      surface-point sets were obtained for each sac using 30-, 15- and six-slice
      sampling. Cubic spline interpolation was used with the 15- and six-slice surface
      point samples to generate coordinates for those 30-slice surface points not
      measured. Interpolated and measured values, the latter from the 30-slice sample,
      were compared and the percent error calculated. Cubic spline interpolation was
      used to determine the coordinates of a standard surface-point sample (3660) for
      each sac in each slice sample. These coordinate data were used to give each sac a
      standard configuration by moving its center of gravity to the origin, aligning
      its inertial axes along the coordinate axes and converting its volume to 1.0 mL.
      In this form, a volume shape descriptor could be generated for each sac that was
      then transformed into a vector containing only shape information. The 20 shape
      vectors of each slice sample were subjected to principal components analysis, and
      principal component scores (PCSs) calculated. The first four PCSs were used to
      define a gestational sac shape score (GSSS-30, GSSS-15 or GSSS-6) for each sac in
      a given slice sample. The characteristics of each set of GSSSs were determined
      and those for the GSSS-15 and GSSS-6 were compared with the GSSS-30
      characteristics. RESULTS: Cubic spline interpolations were very accurate in most
      cases, with means close to 0%, and approximately 95% of the errors being less
      than 10%. GSSS-30 accounted for 67.6% of the shape variance, had a mean of zero
      and an SD of 1.1, was normally distributed and was not related to menstrual age
      (R=-0.16, P=0.51). GSSS-15 and GSSS-6 had essentially the same characteristics.
      No significant differences between individual GSSS-30 values and those for GSSS
      15 or GSSS-6 were found, indicating the absence of a slice sample effect.
      CONCLUSION: Using sophisticated mathematical methods, the gestational sac shape,
      initially represented by the 3D coordinates of 3660 surface points, was converted
      to a single number, the GSSS. This score had the appropriate properties for
      quantitatively characterizing normal, first-trimester gestational sac shapes. As
      it can be obtained from as few as six slices, it should be useful in many
      clinical situations. This novel approach has the potential for providing
      quantitative shape information about a variety of biological shapes and how they
      change over time.

PMID- 17444552
TI  - Percutaneous ultrasound-guided sclerotherapy for complicated fetal intralobar
      bronchopulmonary sequestration.
AB  - Bronchopulmonary sequestration (BPS), which can be intralobar or extralobar, is a
      rare developmental anomaly of the lung characterized by nonfunctional pulmonary
      tissue without communication with the tracheobronchial tree and with an aberrant
      systemic arterial blood supply. The intralobar type is typically within the
      pleural cavity with an arterial feeding vessel generally arising from the
      thoracic aorta and with venous drainage into the left atrium. The prognosis is
      poor in cases diagnosed before 26 weeks' gestation and when there is mediastinal
      shift, polyhydramnios and fetal hydrops. The ideal prenatal management option
      remains undefined. We present a series of three complicated cases of intralobar
      BPS treated prenatally with percutaneous ultrasound-guided fetal sclerotherapy
      (FST). The feeding vessel was successfully accessed percutaneously under
      ultrasound guidance in all cases. FST with polidocanol resulted in complete
      obliteration of the blood flow to the mass. Abnormal Doppler findings, ascites,
      hydrops and polyhydramnios resolved and all patients were delivered at term.
      Antenatal treatment of patients with complicated BPS can be successfully achieved
      with FST, which is a simple and inexpensive technique. Comparison of risks and
      benefits of this approach with other techniques is warranted.

PMID- 17444553
TI  - Transvaginal sonographic measurement of cervical length vs. Bishop score in labor
      induction at term: tolerability and prediction of Cesarean delivery.
AB  - OBJECTIVES: To compare transvaginal sonography for cervical length measurement
      and digital examination for Bishop score assessment in women undergoing labor
      induction at term, to assess their tolerability (in terms of pain) and ability to
      predict need for Cesarean delivery. METHODS: A prospective study was performed on
      249 women admitted for labor induction. Cervical length was measured using
      transvaginal ultrasound examination. A 10-point visual analog scale (VAS) for
      procedure-related pain was obtained. Bishop score was determined just before
      labor induction and another pain score was obtained. Delivery outcome was
      recorded. Analyses were by t-test, Fisher's exact test, receiver-operating
      characteristics (ROC) curves and multivariate logistic regression. RESULTS:
      Transvaginal sonography was significantly less painful than digital examination
      for Bishop score assessment (mean difference in VAS score 3.46; P<0.001).
      Analyses of the ROC curves for cervical length and Bishop score indicated that
      both were predictors of Cesarean delivery (area under the curve 0.611 vs. 0.607;
      P=0.012 vs. P=0.015, respectively) with optimal cut-offs for predicting Cesarean
      delivery of >20 mm for cervical length and Bishop score<or=5. Cervical length had
      superior sensitivity (80% vs. 64%) and marginally better positive (30% vs. 27%)
      and negative (89% vs. 83%) predictive values. Multivariate logistic regression
      analysis revealed that only nulliparity (adjusted odds ratio (AOR) 4.1; 95% CI,
      2.1-8.1; P<0.001) and transvaginal sonographic cervical length>20 mm (AOR 3.4;
      95% CI, 1.4-8.1; P=0.006) were independent predictors of Cesarean delivery.
      CONCLUSIONS: Transvaginal sonography for cervical length measurement is better
      tolerated than digital examination for Bishop score assessment. Both cervical
      length and Bishop score are useful predictors of the need for Cesarean delivery
      following labor induction. A cervical length>20 mm at labor induction at term is
      an independent predictor of Cesarean delivery.

PMID- 17444554
TI  - Accuracy of ultrasound subjective 'pattern recognition' for the diagnosis of
      borderline ovarian tumors.
AB  - OBJECTIVES: To assess the value of pattern recognition for the preoperative
      ultrasound diagnosis of borderline ovarian tumors (BOTs). METHODS: This was a
      prospective study of women who were referred to our regional cancer center with
      the diagnosis of an adnexal mass on a Level II (routine) gynecological ultrasound
      scan. Women with lesions of uncertain nature were referred for a Level III
      (expert) ultrasound scan in our tertiary center. The tumor pattern recognition
      method was used to differentiate between various types of ovarian tumors.
      Morphological features suggestive of BOTs were: unilocular cyst with a positive
      ovarian crescent sign and extensive papillary projections arising from the inner
      wall, or a cyst with a well defined multilocular nodule. The ultrasound findings
      were compared with the final histological diagnosis. RESULTS: A total of 224
      women with an adnexal mass of uncertain nature were referred for an expert scan,
      166 (74.1%) of whom underwent surgery. In this group of women the final
      histological diagnoses were: 99 (60%) benign lesions, 32 (19%) invasive ovarian
      cancer and 35 (21%) BOTs. Using pattern recognition combining the different
      morphological features, a correct preoperative diagnosis of BOT was made in 24/35
      (68.6%) women: area under the receiver-operating characteristics curve 0.812
      (standard error 0.049; 95% CI, 0.716-0.908), sensitivity 0.69 (95% CI, 0.52
      0.81), specificity 0.94 (95% CI, 0.88-0.97), positive likelihood ratio 11.3 (95%
      CI, 5.53-22.8) and negative likelihood ratio 0.34 (95% CI, 0.21-0.55).
      CONCLUSIONS: Ultrasound diagnosis of BOTs is highly specific. However, typical
      features are absent in one-third of cases, which are typically misdiagnosed as
      benign lesions.

PMID- 17444555
TI  - Ultrasound and magnetic resonance imaging in the assessment of a fetal
      intracardiac mass.

PMID- 17444556
TI  - Antenatal diagnosis of bilateral intrathoracic kidneys.

PMID- 17444557
TI  - Preoperative diagnosis of ovarian tumors using Bayesian kernel-based methods.
AB  - OBJECTIVES: To develop flexible classifiers that predict malignancy in adnexal
      masses using a large database from nine centers. METHODS: The database consisted
      of 1066 patients with at least one persistent adnexal mass for which a large
      amount of clinical and ultrasound data were recorded. The outcome of interest was
      the histological classification of the adnexal mass as benign or malignant. The
      outcome was predicted using Bayesian least squares support vector machines in
      comparison with relevance vector machines. The models were developed on a
      training set (n=754) and tested on a test set (n=312). RESULTS: Twenty-five
      percent of the patients (n=266) had a malignant tumor. Variable selection
      resulted in a set of 12 variables for the models: age, maximal diameter of the
      ovary, maximal diameter of the solid component, personal history of ovarian
      cancer, hormonal therapy, very strong intratumoral blood flow (i.e. color score
      4), ascites, presumed ovarian origin of tumor, multilocular-solid tumor, blood
      flow within papillary projections, irregular internal cyst wall and acoustic
      shadows. Test set area under the receiver-operating characteristics curve (AUC)
      for all models exceeded 0.940, with a sensitivity above 90% and a specificity
      above 80% for all models. The least squares support vector machine model with
      linear kernel performed very well, with an AUC of 0.946, 91% sensitivity and 84%
      specificity. The models performed well in the test sets of all the centers.
      CONCLUSIONS: Bayesian kernel-based methods can accurately separate malignant from
      benign masses. The robustness of the models will be investigated in future
      studies.

PMID- 17444558
TI  - In-vivo high-resolution X-ray microtomography for liver and spleen tumor
      assessment in mice.
AB  - The present study sought to validate the use of glycery1-2-oley-1,3-bis-[7-(3
      amino-2,4,6-triiodophenyl)- heptanoate] (DHOG) contrast agent for mouse spleen
      tumor and liver metastasis imaging by high-resolution X-ray microtomography.
      Three groups of female nude mice were compared: controls (n = 5), and mice
      injected with 2.5 x 10(6) STC1 tumor cells in the spleen, imaged at 15 days
      (group G15, n = 5) and at 30 days (group G30, n = 5, of which one died before
      imaging). Micro-CT scans (X-ray voltage, 50 kVp; anode current, 200 microA;
      exposure time, 632 ms; 180 rotational steps resulting in 35 microm isotropic
      spatial resolution) were acquired at 0, 0.75, 2 and 4 h after i.v. injection of
      DHOG. CT number (Hounsfield units: HU) and contrast-to-noise ratios (CNR) were
      determined in three organs. Statistical analysis was performed by Mann-Whitney U
      test. Contrast enhancement in normal spleen and liver increased, respectively to
      1020 +/- 159 and 351 +/- 27 HU over baseline at 4 h, and 482 +/- 3 and 203 +/- 14
      HU on day 6 after a single contrast injection. Automated three-dimensional
      reconstruction and modeling of the spleen provided accurate and quantifiable
      images. Spleen tumor and liver metastases did not take up DHOG, making them
      detectable in contrast to the increased signal in normal tissue. The smallest
      liver metastasis detected measured 0.3 mm in diameter. High-resolution X-ray
      micro-CT in living mice using DHOG contrast agent allowed visualization and
      volume quantification of normal spleen and of spleen tumor and its liver
      metastases.

PMID- 17444559
TI  - The tachykinin tale: molecular recognition in a historical perspective.
AB  - Crystallography, mutational mapping and crosslinking are but a few of the
      experimental techniques that have helped to elucidate the underlying principles
      of molecular recognition between macromolecules and to improve our understanding
      of the evolution of the structure-activity relationship (SAR). While this
      development has been particularly successful for small and rigid ligands and
      substrates that bind to larger hydrophilic biomolecules, our understanding of
      membrane-embedded proteins is still rather limited. This review uses the example
      of the neuropeptide family of tachykinins and their G-protein coupled receptors
      (GPCR) to present how complementary experimental strategies over the past decades
      have nourished and modified conceptual models of the structural requisites of
      molecular recognition and function. Given the little we know, the pertinent
      question is how we proceed from here.

PMID- 17444560
TI  - Discordance in nuchal translucency thickness in the prediction of severe twin-to
      twin transfusion syndrome.
AB  - OBJECTIVE: To examine in monochorionic pregnancies the possible value of
      intertwin discordance in nuchal translucency (NT) thickness in the prediction of
      early fetal death or severe twin-twin transfusion syndrome (TTTS). METHODS: In
      512 monochorionic twin pregnancies NT was measured at 11 to 13 + 6 weeks'
      gestation and regression analysis was used to determine the significance of the
      association between the intertwin discordance in NT and subsequent early fetal
      death or development of severe TTTS requiring endoscopic laser surgery. RESULTS:
      In 412 (80.5%) pregnancies there was a normal outcome, in 58 (11.3%) there was
      severe TTTS requiring endoscopic laser surgery at 18-24 weeks, in 19 (3.7%) there
      was death of one or both fetuses at 13-18 weeks and in 23 (4.5%) there was fetal
      death at 21-38 weeks. In the four outcome groups the median discordance in NT was
      11%, 22%, 35% and 7%, respectively. Significant prediction of early fetal death
      and severe TTTS was provided by the discordance in fetal NT, which was not
      significantly improved by including the discordance in crown-rump length. If the
      discordance in NT was 20% or more, the false positive rate was 20%, the detection
      rate of early fetal death was 63% and the detection rate of severe TTTS was 52%.
      CONCLUSIONS: Discordance in NT of 20% or more is found in about 25% of
      monochorionic twins and in this group the risk of early fetal death or
      development of severe TTTS is more than 30%. If the discordance is less than 20%
      the risk of complications is less than 10%.

PMID- 17444561
TI  - Estimation of fetal weight: reference range at 20-36 weeks' gestation and
      comparison with actual birth-weight reference range.
AB  - OBJECTIVES: To formulate reference charts and equations for estimated fetal
      weight (EFW) from a large sample of fetuses and to compare these charts and
      equations with those obtained for birth weight during the same study period and
      in the same single health authority. METHODS: Biometric data were obtained at 20
      36 weeks' gestation from routine screening examinations spanning 4 years.
      Exclusion criteria were a known abnormal karyotype or congenital malformation and
      multiple pregnancy. No data were excluded on the basis of abnormal biometry. EFW
      was calculated based on Hadlock's formula. We used a polynomial regression
      approach (mean and SD model) to compute a new reference chart for EFW. This chart
      was compared with that of birth weight at 25-36 weeks' gestation during the same
      study period and in the same health authority. RESULTS: 18,959 fetuses were
      included in the study. New charts and equations for Z-score calculations at 20-36
      weeks' gestation are reported. Comparison with the birth-weight chart showed that
      the EFW was noticeably larger at 25-36 weeks' gestation. At 28-32 weeks'
      gestation, the 50th centile for birth weight compared approximately with the 10th
      centile for EFW. CONCLUSION: We present new reference charts and equations for
      EFW. EFW is computed throughout gestation based on measurements in healthy
      fetuses. However, before full term, birth-weight charts reflect a significant
      proportion of growth-restricted fetuses that deliver prematurely. We provide
      additional evidence that comparing EFW with birth-weight charts is misleading.

PMID- 17444562
TI  - The Bayesian approach: a natural framework for statistical modeling.

PMID- 17444563
TI  - Imaging in gynecological disease.

PMID- 17444564
TI  - Development and internal validation of a nomogram to predict macrosomia.
AB  - OBJECTIVE: To develop a nomogram to predict macrosomia with a combination of
      clinical and ultrasound variables. METHODS: Data from 194 women who underwent
      sonographic fetal weight estimation were used to develop and calibrate a nomogram
      to predict fetal macrosomia. The nomogram was subjected to 200 bootstrap
      resamples for internal validation and to reduce overfit bias. An Internet-based
      tool was developed to facilitate use of the nomogram. RESULTS: The macrosomia
      prediction nomogram, based on parity, ethnicity, body mass index and fetal weight
      estimated macrosomia, had good discrimination and calibration before and after
      bootstrapping (area under curve (AUC), 0.860 and 0.850, respectively). The
      predictive accuracy of our nomogram was significantly better than was
      sonographically estimated fetal weight using Hadlock's formula (AUC, 0.740;
      P<0.001). We have provided a web-based interface to predict the individual
      probability of macrosomia. CONCLUSION: We have developed a nomogram to predict
      the individual probability of macrosomia based on clinical and ultrasound
      findings. Our web-based interface should help to guide patients and physicians in
      decision-making.

PMID- 17444565
TI  - Imaging in gynecological disease (1): ultrasound features of metastases in the
      ovaries differ depending on the origin of the primary tumor.
AB  - OBJECTIVE: To describe the gray-scale and color Doppler ultrasound findings of
      metastatic tumors in the ovary according to the origin of the primary tumor.
      METHODS: Information was retrieved retrospectively from 67 patients who had
      undergone preoperative transvaginal gray-scale and color Doppler ultrasound
      examination and who were found subsequently to have metastatic tumors in their
      ovaries. In all women the ultrasound information had been collected prospectively
      using a standardized examination technique and predefined definitions of
      ultrasound characteristics. Stored ultrasound images were used only to describe
      retrospectively the external surface of the metastatic tumors. Information on
      presenting symptoms and on whether the patient had been treated for a malignancy
      in the past was retrieved retrospectively from patient records. RESULTS: Most
      (95%) ovarian metastases were solid, multilocular-solid or multilocular. Almost
      all (38/41, 93%) metastases that derived from the stomach, breast, lymphoma or
      uterus were solid, while most (16/22, 73%) metastases deriving from the colon,
      rectum, appendix or biliary tract were multilocular or multilocular-solid
      (P<0.0001). Metastases that derived from the colon, rectum, appendix or biliary
      tract were larger compared with those from the stomach, breast, lymphoma or
      uterus (median maximum diameter, 122 (range, 16-200) mm vs. 71 (range, 27-170)
      mm, P=0.02). In addition, irregular external borders were more common (19/22
      (86%) vs. 19/41 (46%), P=0.002), as were papillary projections (6/22 (27%) vs.
      2/41 (5%), P=0.011). They also appeared to be less vascularized, with 64% (14/22)
      manifesting moderate-to-abundant vascularization at color Doppler examination in
      comparison to 88% (36/41) of the ovarian metastases from stomach, breast,
      lymphoma or uterus (P=0.024). CONCLUSION: Ovarian metastases derived from
      lymphoma or from tumors in the stomach, breast and uterus are solid in almost all
      cases, whereas those derived from the colon, rectum or biliary tract manifest
      more heterogeneous morphological patterns, most being multicystic with irregular
      borders.

PMID- 17444567
TI  - Evaluation of fetal regional cerebral blood perfusion using power Doppler
      ultrasound and the estimation of fractional moving blood volume.
AB  - OBJECTIVE: To standardize the evaluation of regional fetal brain blood perfusion,
      using power Doppler ultrasound (PDU) to estimate the fractional moving blood
      volume (FMBV) and to evaluate the reproducibility of this estimation. METHODS:
      Brain blood perfusion was evaluated in 35 normally grown fetuses at 28-30 weeks
      of gestation, using PDU. The following cerebral regions were included in the PDU
      color box: anterior sagittal, complete sagittal, basal ganglia, and cerebellar.
      Ten consecutive good-quality images of each anatomical plane were recorded and
      the delimitation of the region of interest (ROI) was performed off-line. FMBV was
      quantified in the ROI of all images and the mean considered as the final value.
      Differences between regions, variability, reproducibility and agreement between
      observers were assessed. RESULTS: Power Doppler images of the described
      anatomical planes were obtained in all cases, regardless of fetal position. The
      median time for the acquisition of the images was 7 (range 4-12) min. Mean
      (range) FMBV values were: anterior sagittal, 16.5 (10.7-22.8)%, inter-patient
      coefficient of variation (CV) 0.22; complete sagittal, 13.5 (8.8-16.1)%, CV 0.27;
      basal ganglia, 18.3 (10.7-27.6)%, CV 0.27; and cerebellar, 6.6 (3.0-11.0)%, CV
      0.38. There were statistically significant differences in FMBV between cerebellar
      and complete sagittal ROIs with the frontal and basal ganglia regions.
      Reproducibility analyses showed an intraclass correlation coefficient of 0.91
      (95% CI 0.67-0.97) and an interclass correlation coefficient of 0.87 (95% CI 0.70
      0.94). Interobserver agreement showed a mean difference between observers of -0.2
      (SD 2.7) with 95% limits of agreement -5.6 to 5.2. CONCLUSIONS: When the regions
      of interest are well defined, the FMBV estimate offers a method to quantify blood
      flow perfusion in different fetal cerebral areas. There appear to be regional
      differences in FMBV within the fetal brain.

PMID- 17444568
TI  - Contribution of three-dimensional computed tomography in the assessment of fetal
      skeletal dysplasia.
AB  - OBJECTIVE: To compare the diagnostic accuracy of two-dimensional (2D) ultrasound
      and three-dimensional (3D) computed tomography (CT) for the diagnosis of fetal
      skeletal anomalies. METHODS: Eleven pregnant women underwent 2D ultrasound and 3D
      CT. Ten fetuses presented skeletal anomalies on 2D ultrasound and one fetus had a
      normal ultrasound exam but a familial history of osteopetrosis. We compared
      retrospectively the diagnoses established on 2D ultrasound and 3D-CT with the
      neonatal and/or postmortem work-up, which were used as the gold standard.
      RESULTS: 2D ultrasound provided the correct diagnosis in only two of the 11
      cases. CT yielded the correct diagnosis in eight; in six of these, 2D ultrasound
      had been inconclusive. 3D-CT was more accurate than was 2D ultrasound in
      visualizing vertebral anomalies (abnormal shape of the vertebral bodies, abnormal
      interpedicular distance), pelvic bone malformations (delayed ossification of the
      pubic bones, abnormal acetabular shape) and enlarged metaphysis or synostoses in
      long bones. In three cases, neither 2D ultrasound nor CT provided the correct
      diagnosis. CONCLUSION: In this series, which included a variety of skeletal
      dysplasias, 3D-CT had a better diagnostic yield than did 2D ultrasound. Both
      imaging techniques are useful in the management of fetal dysplasia; 2D ultrasound
      is a useful screening test and 3D-CT is a valuable complementary diagnostic tool.

PMID- 17444569
TI  - Self-assembly of photoresponsive [2.2]paracyclophane-derivative nanostripes on a
      conducting surface with modified wettability.

PMID- 17444570
TI  - The synthesis and fabrication of one-dimensional nanoscale heterojunctions.
AB  - There are a variety of methods for synthesizing or fabricating one-dimensional
      (1D) nanostructures containing heterojunctions between different materials. Here
      we review recent developments in the synthesis and fabrication of heterojunctions
      formed between different materials within the same 1D nanostructure or between
      different 1D nanostructures composed of different materials. Structures
      containing 1D nanoscale heterojunctions exhibit interesting chemistry as well as
      size, shape, and material-dependent properties that are unique when compared to
      single-component materials. This leads to new or enhanced properties or
      multifunctionality useful for a variety of applications in electronics,
      photonics, catalysis, and sensing, for example. This review separates the methods
      into vapor-phase synthesis, solution-phase synthesis, template-based synthesis,
      and other approaches, such as lithography, electrospinning, and assembly. These
      methods are used to form a variety of heterojunctions, including segmented,
      core/shell, branched, or crossed, from different combinations of semiconductor,
      metal, carbon, and polymeric materials.

PMID- 17444571
TI  - Asymmetric total syntheses of platensimycin.

PMID- 17444572
TI  - Rheumatology nurses' work-related empowerment.
AB  - OBJECTIVE: The purpose of the study was to investigate rheumatology nurse
      specialists' work related empowerment. METHOD: Nine nurses undertaking graduate
      studies were asked to write an essay on 'What work related skills does the
      rheumatology nurse need to master?' In addition, one interview was conducted. The
      material was analysed using the method of inductive content analysis. RESULTS:
      The following key areas of work related empowerment were identified as important:
      knowledge about rheumatic diseases; treatments and follow up monitoring care;
      knowledge about patient education and counselling; collaboration and the ability
      to co operate; mastery of manual skills and development of the quality of nursing
      care for patients with rheumatic disease. CONCLUSION: The study contributes to a
      better understanding of work related empowerment among rheumatology nurses. The
      results of the study can be used to develop the role components of healthcare
      professionals who attend patients with rheumatic disease.

PMID- 17444573
TI  - Administration of Cyperus rotundus tubers extract prevents weight gain in obese
      Zucker rats.
AB  - Cyperus rotundus L. (Cyperaceae; C. rotundus) is an Indian medicinal plant
      demonstrated to exert multiple health benefits. The purpose of the present study
      was to test the biological efficacy of C. rotundus tubers extract on weight
      control in obese Zucker rats. It was demonstrated that administration of 45 or
      220 mg/kg/day of C. rotundus tubers hexane extract for 60 days in Zucker rats
      induced a significant reduction in weight gain without affecting food consumption
      or inducing toxicity. In vitro, 250 microg/mL of this extract was able to
      stimulate lipolysis in 3T3-F442 adipocytes suggesting that this medicinal plant
      contains activators of beta-adrenoreceptors (AR). The binding assay performed on
      the rat beta3-AR isoform, known to induce thermogenesis, demonstrated that C.
      rotundus tubers extract can consistently and effectively bind to this receptor.
      These data suggest that the effect on weight gain exerted by C. rotundus tubers
      extract may be mediated, at least partially, through the activation of the beta3
      AR. In conclusion, C. rotundus tubers extract prove to be a new herbal supplement
      for controlling body weight preferentially in beta3-AR sensitive species.

PMID- 17444574
TI  - Yellow tea is more potent than other types of tea in suppressing liver toxicity
      induced by carbon tetrachloride in rats.
AB  - The present study compared the effects of six Chinese teas categorized by their
      production process: green, white, yellow, oolong, black and pu-erh teas, on
      carbon tetrachloride (CCl4)-induced liver injury. Wistar rats were given ad
      libitum the Chinese teas prepared according to the home-style methods for 1 week,
      and then intraperitoneally injected with CCl4 (1 mg/kg body weight) or olive oil
      as a vehicle. The yellow tea significantly ameliorated the increase in the
      activity of the alanine- and aspartate-aminotransferases in plasma. Thus, the
      drinking of yellow tea may contribute to protection against liver injury.

PMID- 17444575
TI  - In vitro antifungal activity of extract and plumbagin from the stem bark of
      Diospyros crassiflora Hiern (Ebenaceae).
AB  - In this study the methanol/dichloromethane (1:1) extract and plumbagin isolated
      from extract of stem barks of Diospyros crassiflora were tested for their
      antifungal activity against 12 strains of yeast pathogens and filamentous fungi:
      Candida albicans, Candida glabrata, Candida krusei, Candida tropicalis,
      Cryptococcus neoformans, Aspergillus niger, Aspergillus flavus, Alternaria sp.,
      Cladosporium sp., Geotrichum candidum, Fusarium sp. and Penicillium sp. The
      growth of all fungi strains tested was inhibited by the extract and plumbagin.
      The diameter of inhibition zones varied from 12 to 18 mm and from 21 to 35 mm for
      the extract and plumbagin, respectively. The MIC values ranged from 12.5 to 25
      mg/mL for the extract and 0.78-3.12 microg/mL for plumbagin. It is therefore
      suggested that extracts from the stem bark of Diospyros crassiflora could be used
      traditionally in the treatment of fungal infections. Compared with ketoconazole
      used as a standard antifungal, plumbagin could be considered as a promising
      antifungal agent.

PMID- 17444576
TI  - Evidence of effectiveness of herbal antiinflammatory drugs in the treatment of
      painful osteoarthritis and chronic low back pain.
AB  - Treatment with herbal medicines is very popular in Europe. In order to get
      information on the evidence of effectiveness of oral herbal medicines in the
      treatment of pain in the joints or lower back, OVID(MEDLINE), PUBMED and COCHRANE
      COLLABORATION LIBRARY were searched back to 1985 for systematic reviews. The
      level of evidence of effectiveness was defined as strong - at least two
      confirmatory studies demonstrating a clinical relevant effect, moderate - one
      confirmatory study with a clinical relevant effect and/or multiple exploratory
      studies of good quality; otherwise the evidence was insufficient or conflicting
      in the case of inconsistent findings. Fifteen systematic reviews were identified.
      The evidence of effectiveness was strong for a proprietary unsaponifiable avocado
      soybean fraction and Harpagophytum preparations containing > 50 mg harpagoside in
      the daily dosage, moderate for ginger and a proprietary rose hip and seed powder,
      insufficient for Boswellia serrata gum resin and other herbal preparations and
      inconsistent for a proprietary willow bark extract. Further rigorous studies are
      required to confirm the usefulness of herbal medicines in the treatment of
      osteoarthritic complaints and chronic low back pain in order to enable acceptance
      of the herbal medicines into the treatment guidelines.

PMID- 17444577
TI  - Analgesic and antiinflammatory activity of Cyclamen repandum S. et S.
AB  - According to folk medicine some species belonging to the genus Cyclamen were used
      for their biological activities. Early investigation of the different species of
      the genus resulted in the isolation of triterpenic saponins. No phytochemical and
      biological data are available on C. repandum. As part of a series of
      phytochemical investigations for bioactive compounds from medicinal plants,
      Cyclamen repandum S. et S. was investigated. The present study sought to find the
      antiinflammatory and antinociceptive activities of C. repandum tubers in rats and
      mice. A preliminary screening was conducted with three different extracts in the
      tests used, particularly the paw edema and the writhing tests. Subsequently some
      saponins isolated from the ME extract, the more effective one, have been
      identified. This paper also describes the results of fractionation and bioassay
      guided chemical studies. Chemical investigation of the active extract afforded
      the isolation and characterization of six triterpenic saponins. The possible
      antiinflammatory and analgesic properties were investigated as the saponin
      content of the fractions allows to speculate on such aspect.

PMID- 17444578
TI  - Development and biological assessment of fully water-soluble helical aromatic
      amide foldamers.

PMID- 17444580
TI  - Honeycomb-patterned photoluminescent films fabricated by self-assembly of
      hyperbranched polymers.

PMID- 17444579
TI  - Hiyama reactions of activated and unactivated secondary alkyl halides catalyzed
      by a nickel/norephedrine complex.

PMID- 17444581
TI  - Extremely stable photoinduced charge separation in a colloidal system composed of
      semiconducting niobate and clay nanosheets.

PMID- 17444582
TI  - 2006 annual research and education meeting of the Spondyloarthritis Research and
      Therapy Network (SPARTAN).

PMID- 17444583
TI  - Acute exacerbation of preexisting interstitial lung disease after administration
      of etanercept for rheumatoid arthritis.
AB  - A 70-year-old woman with a 6-year history of seropositive rheumatoid arthritis
      (RA) and asymptomatic interstitial lung disease (ILD) began taking etanercept for
      ongoing arthritis despite treatment with methotrexate (MTX) and bucillamine. MTX
      was discontinued before introduction of etanercept. She developed lung injury 8
      weeks after starting etanercept. Etanercept was discontinued and oral
      prednisolone 40 mg/day was begun, and her clinical findings gradually improved.
      Lung injury, although rare, is a recently noticed, potentially fatal adverse
      effect of all 3 licensed biological anti-tumor necrosis factor (TNF) agents. We
      recommend caution in the use of anti-TNF agents in elderly RA patients with
      preexisting ILD.

PMID- 17444584
TI  - Amitriptyline to relieve pain in juvenile idiopathic arthritis: a pilot study
      using Bayesian metaanalysis of multiple N-of-1 clinical trials.
AB  - OBJECTIVE: Using serial N-of-1 trials and subsequent analysis with Bayesian
      methods may allow study of therapies using small numbers of subjects. Our
      research questions were: (1) Can serial N-of-1 trials analyzed with Bayesian
      statistical techniques be used to estimate the population effect of a therapeutic
      intervention? (2) Compared to placebo, how likely is it that low-dose
      amitriptyline therapy in children aged 10-18 years with active polyarticular
      course juvenile idiopathic arthritis (JIA) results in a significant improvement
      in pain? METHODS: Six children (age 10.3-16.3 yrs, 4 girls) were enrolled. There
      were 3 pairs of randomized, double-blinded treatments (amitriptyline 25 mg or
      placebo) per participant. Each treatment lasted 2 weeks, with a 1 week washout.
      The primary outcome was pain, measured by 10 cm visual analog scale. Assessments
      were at the beginning and end of each treatment. A Bayesian statistical model was
      used to determine the treatment effect. Values < 0 indicated superiority of
      amitriptyline. RESULTS: Bayesian techniques were used successfully to obtain
      estimates of population effect, despite the small number of participants. The
      mean treatment effect for pain was 0.67 (SD 0.89, 95% credible interval -0.99,
      2.55). The probability that the treatment effect was < 0 was only 16%.
      CONCLUSION: These methods can be used successfully to estimate population effects
      when sample sizes are small. It is unlikely that amitriptyline reduced pain by a
      clinically significant amount in these children with polyarticular JIA. These
      methods may be particularly suited to pilot studies and the study of rare
      illnesses.

PMID- 17444585
TI  - Antiendothelial cell antibodies in patients with Wegener's granulomatosis:
      prevalence and correlation with disease activity and manifestations.
AB  - OBJECTIVE: Previous studies in small cohorts of patients with Wegener's
      granulomatosis (WG) or antineutrophil cytoplasmic antibody (ANCA) associated
      vasculitis have yielded conflicting data regarding the prevalence of
      antiendothelial cell antibodies (AECA), ranging from 8% to 100%, and the use of
      AECA as a measure of disease activity. We examined a large, well-characterized
      cohort of patients with WG and active disease for the presence of AECA. METHODS:
      Serum from subjects with WG who participated in a clinical therapeutic trial was
      collected at baseline, when all subjects had active disease. Clinical
      manifestations and disease activity were documented using the Birmingham
      Vasculitis Activity Score for WG (BVAS/WG). Serum AECA (IgG) was measured by cyto
      ELISA using unfixed human umbilical vein endothelial cells (HUVEC). The AECA
      positivity cutoff was determined using 71 healthy control samples. Statistical
      analyses utilized Student's t test, chi-square and Fisher's exact tests, and
      linear regression. RESULTS: AECA were detected in 34 of 173 (20%) evaluated serum
      samples. Mean BVAS/WG did not differ between patients with (7.3 +/- 3.2) or
      without AECA (7.0 +/- 3.3) (p = 0.58). Among the 34 patients positive for AECA,
      the antibody titer did not correlate with disease activity (BVAS/WG; r = 0.09, p
      = 0.60). There were no statistically significant differences in the frequency of
      major clinical manifestations between patients with or without AECA. CONCLUSION:
      AECA, as measured using HUVEC, are not highly prevalent among patients with
      active WG, are not associated with specific clinical manifestations, and do not
      correlate with level of disease activity.

PMID- 17444586
TI  - Prevalence and characteristics of moderate to severe pulmonary hypertension in
      systemic sclerosis with and without interstitial lung disease.
AB  - OBJECTIVE: To determine the prevalence and characteristics of moderate to severe
      pulmonary hypertension (PH) in patients with systemic sclerosis (SSc) with and
      without interstitial lung disease (ILD). METHODS: We retrospectively studied
      clinical and functional characteristics of 197 consecutive patients with SSc who
      had undergone a screening echocardiography to detect PH. RESULTS: Moderate to
      severe PH was suspected in 36 patients (18.3%) and confirmed in 32 who underwent
      right heart catheterization. The prevalence of PH did not differ between patients
      with limited and patients with diffuse cutaneous SSc. PH was detected in 12/67
      (17.9%) patients without ILD vs 24/110 (21.8%) patients with ILD (p not
      significant). In patients with ILD, a lower PaO2 appeared as the unique
      independent factor significantly associated with PH, regardless of the extent of
      fibrosis. In 3 patients out of 9 (33.3%) with ILD and significantly restrictive
      disease, PH was out of proportion to the degree of fibrosis. In patients with no
      ILD, a higher grade of dyspnea appeared as the unique independent factor
      associated with PH. In patients with no ILD, altered DLCO was the sole indicator
      of the pulmonary function tests associated with PH (best cutoff value 72%). DLCO
      correlated with systolic pulmonary arterial pressure only in patients with no
      ILD. CONCLUSION: Prevalence of moderate to severe PH was similar in SSc patients
      with and those without ILD. In patients with ILD, a lower PaO2 was the unique
      independent indicator associated with PH. In some patients with severe ILD, PH
      was out of proportion to the degree of fibrosis. A linear correlation between
      DLCO and systolic pulmonary arterial pressure was observed only in patients
      without ILD. All these indicators should assist identification of patients with
      or without ILD requiring diagnostic procedures for PH before annual screening.

PMID- 17444587
TI  - Association of polymorphisms in the IL1B and IL2 genes with susceptibility and
      severity of systemic sclerosis.
AB  - OBJECTIVE: To investigate possible associations of 9 single-nucleotide
      polymorphisms in the IL10, IL1B, IL1A, IL1RN, IL2, LTA, and IL6 genes with
      susceptibility to systemic sclerosis (SSc), and with clinical subtype of SSc
      patients. METHODS: A total of 78 patients with SSc [diffuse SSc (dcSSc), n = 31;
      limited SSc, (lcSSc), n = 47] and 692 healthy blood donors were genotyped for the
      following polymorphisms: IL10 T-3575A, IL10 A-1082G, IL1B C-31T, IL1B C-511T,
      IL1A C-889T, IL1RN A9589T, IL2 T-384G, LTA T-91G, and IL6 G-174C. RESULTS:
      Alleles in IL1B-31 and IL1B-511 showed a significantly different distribution
      between cases and controls. Carriers of at least one copy of the IL1B-31-C allele
      had an increased risk of SSc [odds ratio (OR) 2.8, 95% confidence interval (CI)
      1.6-5.2, p < 0.001], while a similar strong association was also evident for IL1B
      511-T carriers (OR 3.1, 95% CI 1.7-5.7, p < 0.001). Interestingly, carriers of
      the IL2-384-G allele were significantly more frequent among patients with lcSSc
      (80.8%), compared to patients with the diffuse subtype (45.1%) (OR 5.1, 95% CI
      1.8-14.3, p = 0.001) and in subjects positive to anticentromere antibodies (OR
      4.2, 95% CI 1.5-11.9, p = 0.007). Lastly, the distribution of the IL2-384
      genotype showed statistically significant differences between controls and
      patients with lcSSc (OR 3.5, 95% CI 1.7-7.4, p < 0.001). There were no
      differences between patients with dcSSc and controls. CONCLUSION: IL1B and IL2
      gene polymorphisms may be involved in susceptibility to SSc. Moreover, the IL2
      384-G allele may be a marker for the limited phenotype of SSc.

PMID- 17444588
TI  - Screening for proteinuria in patients with lupus: a survey of practice
      preferences among American rheumatologists.
AB  - OBJECTIVE: Screening for proteinuria in patients with lupus requires a diagnostic
      method with adequate validity to detect early disease. Recent studies have called
      into question the validity of qualitative proteinuria measurements. We set out to
      assess if American rheumatologists have changed their practice preferences in
      response to these data. METHODS: Using an online survey tool, we questioned
      practicing physicians, who were members of the American College of Rheumatology
      in 2005, about their demographic characteristics and preferred method to detect
      proteinuria in patients with known lupus. RESULTS: In our survey, 64.6% of 473
      respondents reported using qualitative urinalysis (dipstick) as the primary
      method of screening for proteinuria. The remaining 32.7% preferred quantitative
      measurements (spot protein to creatinine ratio 16.8%; 24-h protein 7.8%;
      microalbuminuria 4.1%; 24-h protein to creatinine ratio 4.1%). Rheumatologists in
      practice for more than 10 years were more likely than those in practice for less
      time to use a qualitative method. Although physicians using dipsticks were most
      likely to use 1+ as a cutoff for significant proteinuria, 28.5% report using a
      threshold of > or = 2+. CONCLUSION: Despite recent reports describing the
      inadequacy of urine dipstick as a measurement for low-grade proteinuria, the
      majority of practicing rheumatologists are utilizing that method for screening in
      patients with lupus. Because early detection of lupus nephritis has implications
      for prevention of renal associated morbidity and mortality, these findings should
      prompt further investigation of the adequacy and role of urine dipstick as a
      screening tool for lupus.

PMID- 17444589
TI  - Response to pneumococcal vaccine in patients with early rheumatoid arthritis
      receiving infliximab plus methotrexate or methotrexate alone.
AB  - OBJECTIVE: We assessed whether the addition of anti-tumor necrosis factor (TNF)
      agent to methotrexate (MTX) therapy might alter the response of patients with
      rheumatoid arthritis (RA) to pneumococcal vaccination. METHODS: Seventy patients
      with early RA (n = 20, 36, and 14 in the infliximab 3 mg/kg plus MTX, infliximab
      6 mg/kg plus MTX, and placebo plus MTX groups, respectively) were included in an
      analysis of patients enrolled in an ASPIRE substudy. Patients received 0.5 ml
      pneumococcal vaccine (Pneumovax) 34 weeks after initiation of study treatment;
      patient sera were collected 4 weeks later (week 38). Antibody responses were
      tested using enzyme immunoassay methods for reactivity to a panel of 12 serotypes
      of the pneumococcal vaccine. RESULTS: No significant difference in response to
      Pneumovax was observed between the infliximab plus MTX and placebo plus MTX
      groups. Roughly 80%-85% of patients responded to at least one serotype; however,
      only 20%-25% of patients in the different treatment groups responded to at least
      6 different serotypes. Comparable proportions of patients in the 3 treatment
      groups responded to an increasing number (> or = 1 to > or = 6) of different
      serotypes. Patients < 45 years of age and those receiving oral corticosteroids
      generally appeared to respond better than those age 45 to 65 years and those not
      receiving oral corticosteroids. CONCLUSION: All treatment groups in this study
      had lower responses to vaccine than would be expected in the normal population.
      However, the addition of the anti-TNF agent infliximab to MTX therapy did not
      appear to affect the response of patients with RA to pneumococcal vaccination.

PMID- 17444590
TI  - Validation of patient-reported joint counts in rheumatoid arthritis and the role
      of training.
AB  - OBJECTIVE: To demonstrate the effectiveness of simple training on improving the
      ability of patients with rheumatoid arthritis (RA) to assess joint swelling, and
      to validate the use of a computerized questionnaire, the Health Assessment
      Questionnaire (HAQ-ulous), to collect patient-reported tender and swollen joint
      counts. METHODS: Sixty patients completed the HAQ-ulous, reporting pain and
      swelling of the 28 joints included in the Disease Activity Score-28. A
      rheumatologist blinded to the patients' responses assessed each joint for the
      presence of tenderness and swelling. At followup visits, 30 patients received
      training in distinguishing a swollen joint from a chronically enlarged joint,
      completed the HAQ-ulous again, and were reassessed by the physician. RESULTS: At
      the initial visit, a strong correlation was shown between patient- and clinician
      reported tender joints [Pearson correlation coefficient (r(p)) = 0.79; p <
      0.0001]. Correlation between patient- and clinician-reported swollen joints was
      less robust (r(p) = 0.41; p = 0.001). Following training at the second visit,
      agreement between patients and the clinician improved for both tender joints
      (r(p) = 0.94; p < 0.0001) and swollen joints (r(p) = 0.93; p < 0.0001).
      CONCLUSION: With simple training in distinguishing swollen joints from
      chronically enlarged joints, the majority of patients are able to accurately
      assess joint swelling. Objective tools, such as the HAQ-ulous, that incorporate
      patient-reported outcomes are a valuable and reliable addition to standard
      clinical practice for monitoring patients with RA.

PMID- 17444591
TI  - Beneficial action of statins in patients with rheumatoid arthritis in a large
      observational cohort.
AB  - OBJECTIVE: To analyze the possible beneficial effects of statins on the disease
      activity of patients with rheumatoid arthritis (RA) using a database from a large
      observational cohort study. METHODS: We studied a total of 7512 patients enrolled
      in a single-institute based prospective observational cohort of RA patients
      (IORRA); their information was collected biannually. In this study, cross
      sectional data of 4152 patients (female 83.3%, average age 58.4 yrs) in October
      2003 were analyzed (Mann-Whitney U-test). RESULTS: Among 4152 patients with RA,
      279 (6.7%) were taking statins; patients taking statins had lower C-reactive
      protein (0.85 vs 1.24 mg/dl, respectively) and lower swollen joint counts (1.80
      vs 2.55), but more frequently used corticosteroids (2.88 vs 2.40 mg/day) compared
      to patients not taking statins. Serum cholesterol level was closely related to
      the use of corticosteroids. Thus, an adjustment with the dose of corticosteroid
      was conducted; even taking account of the effects of steroids, RA disease
      activity indicated by patient's assessment for pain, physician's assessment, and
      swollen joint counts was significantly lower in patients with statins compared to
      those without. CONCLUSION: This study indicates that statins have beneficial
      effects in reducing RA disease activity in the daily practice of rheumatology.

PMID- 17444592
TI  - Influence of nonclassical cardiovascular risk factors on the accuracy of
      predicting subclinical atherosclerosis in rheumatoid arthritis.
AB  - OBJECTIVE: To determine whether nontraditional risk factors increase the accuracy
      of predicting the presence of carotid artery plaque based on traditional
      cardiovascular risk factors only in patients with rheumatoid arthritis (RA).
      METHODS: We identified risk factors that were independently associated with
      ultrasonographically located plaque. In predicting carotid artery plaque, the
      area under the curve (AUC) of the receiver-operating characteristic (ROC) curve
      for the combination of traditional and nontraditional risk factors was compared
      to the AUC of the ROC curve for traditional risk factors and nontraditional risk
      factors considered separately in 91 patients with RA. RESULTS: Thirty-one (34%)
      patients had carotid artery plaque. The 3 traditional risk factors of age > 55
      years, hypertension, and ever-smoking, and the 3 nontraditional risk factors of a
      disease duration > 8 years, polymorphonuclear cell count > 4.5 x 10(6)/l, and
      hypothyroidism were each independently associated with the presence of plaque
      (odds ratios 2.08-8.78; p = 0.001-0.02). The percentage of patients with plaque
      was 0, 10%, 50%, and 83% in patients with 0-1, 2, 3, and 4-6 of these risk
      factors, respectively. In predicting plaque, the AUC of the ROC curve for the
      combination of traditional and nontraditional risk factors (0.90 +/- 0.03) was
      greater than that for either traditional (0.80 +/- 0.05; p = 0.006) or
      nontraditional (0.80 +/- 0.04; p = 0.005) risk factors considered separately.
      CONCLUSION: The combination of disease duration, polymorphonuclear cell counts,
      and thyroid status increased the accuracy of predicting subclinical atheroma in
      patients with RA. We believe that our findings merit external validation.

PMID- 17444593
TI  - Safety and efficacy of adalimumab in treatment of patients with psoriatic
      arthritis who had failed disease modifying antirheumatic drug therapy.
AB  - OBJECTIVE: To demonstrate the safety and efficacy of adalimumab for the treatment
      of active psoriatic arthritis (PsA) in patients with an inadequate response to
      disease modifying antirheumatic drugs (DMARD). METHODS: In a placebo controlled,
      double-blind, randomized, multicenter study, patients were treated for 12 weeks
      with subcutaneous injections of adalimumab 40 mg every other week (eow) or
      placebo, followed by a period of open-label treatment with adalimumab 40 mg eow.
      The primary efficacy endpoint was the percentage of patients who met the American
      College of Rheumatology (ACR20) core criteria at Week 12. Secondary efficacy
      measures included the modified Psoriatic Arthritis Response Criteria (PsARC) and
      assessments of disability, psoriatic lesions, and quality of life. For missing
      data, nonresponder imputation was used for ACR and PsARC scores and last
      observation carried forward for other measures. RESULTS: A total of 100 patients
      received study drug (51 adalimumab, 49 placebo). At Week 12, an ACR20 response
      was achieved by 39% of adalimumab patients versus 16% of placebo patients (p =
      0.012), and a PsARC response was achieved by 51% with adalimumab versus 24% with
      placebo (p = 0.007). At Week 12, measures of skin lesions and disability were
      statistically significantly improved with adalimumab. After Week 12, open-label
      adalimumab provided continued improvement for adalimumab patients and initiated
      rapid improvement for placebo patients, with ACR20 response rates of 65% and 57%,
      respectively, observed at Week 24. Serious adverse events had similar frequencies
      during therapy with placebo (4.1%), blinded adalimumab (2.0%), and open-label
      adalimumab (3.1%). No serious infections occurred during adalimumab therapy.
      CONCLUSION: In this study of patients who had active PsA and a previous,
      inadequate response to DMARD therapy, adalimumab was well tolerated and
      significantly reduced the signs, symptoms, and disability of PsA during 12 weeks
      of blinded and 12 weeks of open-label therapy. Adalimumab also improved psoriasis
      in these patients.

PMID- 17444594
TI  - Vascular architecture: is it a helpful histopathological biomarker for
      hepatocellular carcinoma?
AB  - Hepatocellular carcinoma (HCC) remains one of the major public health problems
      throughout the world. Although originally associated with tumorigenic processes,
      liver angiogenesis has also been observed in the context of different liver
      inflammatory, fibrotic, and ischemic conditions. Here we investigate the fractal
      dimension as a quantitator of non-Euclidean two-dimensional vascular geometry in
      a series of paired specimens of primary HCC and surrounding non-tumoral tissue,
      and discuss why this parameter might provide additional information regarding
      cancer behavior. The application of fractal geometry to the measurement of liver
      vascularity and the availability of a computer-aided quantitative method can
      eliminate errors in visual interpretation, and make it possible to obtain closer
      to-reality numerals that are compulsory for any measurement process.

PMID- 17444595
TI  - Proteomic analysis of the serum in patients with idiopathic pulmonary arterial
      hypertension.
AB  - Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease of unknown
      etiology. The exact pathogenesis of pulmonary arterial hypertension is still not
      well known. In the past decades, many protein molecules have been found to be
      involved in the development of IPAH. With proteomic techniques, profiling of
      human plasma proteome becomes more feasible in searching for disease-related
      markers. In present study, we showed the protein expression profiles of the serum
      of IPAH and healthy controls after depleting a few high-abundant proteins in
      serum. Thirteen spots had changed significantly in IPAH compared with healthy
      controls and were identified by LC-MS/MS. Alpha-1-antitrypsin and vitronectin
      were down-regulated in IPAH and may be valuable candidates for further
      explorations of their roles in the development of IPAH.

PMID- 17444596
TI  - Study progress on mechanism of severe acute pancreatitis complicated with hepatic
      injury.
AB  - Study on the action mechanism of inflammatory mediators generated by the severe
      acute pancreatitis (SAP) in multiple organ injury is a hotspot in the surgical
      field. In clinical practice, the main complicated organ dysfunctions are shock,
      respiratory failure, renal failure, encephalopathy, with the rate of hepatic
      diseases being closely next to them. The hepatic injury caused by SAP cannot only
      aggravate the state of pancreatitis, but also develop into hepatic failure and
      cause patient death. Its complicated pathogenic mechanism is an obstacle in
      clinical treatment. Among many pathogenic factors, the changes of vasoactive
      substances, participation of inflammatory mediators as well as OFR (oxygen free
      radical), endotoxin, etc. may play important roles in its progression.

PMID- 17444597
TI  - Correlation of serum arylesterase activity on phenylacetate estimated by the
      integrated method to common classical biochemical indexes of liver damage.
AB  - The correlation of serum arylesterase (PON1) activity on phenylacetate determined
      by an integrated method to classical biochemical indexes of liver damage was
      investigated for the use of PON1 activity to evaluate liver damage. PON1 reaction
      curve as absorbance at 270 nm for 0.20 mmol/L phenylacetate hydrolysis was
      analyzed by the integrated method to determine maximal PON1 reaction rate.
      Classical biochemical indexes of liver damage were determined routinely. The 95%
      confidence threshold of PON1 activity in sera from healthy individuals was 2.12
      mkat/L [(4.73+/-1.31) mkat/L, n=105]. PON1 activity in clinical sera was closely
      correlated to serum albumin, total protein and the ratio of albumin to globulins,
      but was weakly correlated to both direct and total bilirubin in serum. There were
      no correlations of PON1 activity to gamma-glutamyltransferase, alkaline
      phosphatase, alanine aminotransferase and aspartate aminotransferase. Among 127
      clinical sera with PON1 activity>2.12 mkat/L, there were 92% healthy individuals
      examined by albumin, 90% healthy individuals examined by total protein, 88%
      healthy individuals examined by total bilirubin, 86% healthy individuals examined
      by direct bilirubin and 64% healthy individuals examined by the ratio of albumin
      to globulins, respectively. In each group of healthy individuals judged by
      classical biochemical indexes of close correlation to PON1 activity, percentage
      of healthy individuals examined by PON1 activity was always >80%. These results
      suggested PON1 activity on phenylacetate estimated by the integrated method was
      also suitable for the evaluation of liver damage.

PMID- 17444598
TI  - Diffusion tensor imaging of the brain in patients with Alzheimer's disease and
      cerebrovascular lesions.
AB  - BACKGROUND: Recent autopsy study showed a high incidence of cerebrovascular
      lesions in Alzheimer's disease (AD). To assess the impact of cerebrovascular
      pathology in AD, we used diffusion tensor imaging (DTI) to study AD patients with
      and without cerebrovascular lesions. MATERIALS AND METHODS: Conventional and DTI
      scans were obtained from 10 patients with probable AD, 10 AD/V patients (probable
      AD with cerebrovascular lesions) and ten normal controls. Mean diffusivity (D)
      and fractional anisotropy (FA) values of some structures involved with AD
      pathology were measured. RESULTS: D value was higher in AD patients than in
      controls in hippocampus and the cingulate gyrus. In AD/V patients, increased D
      value was found in the same structures and also in the thalamus and basal ganglia
      compared to controls. There was a significant difference of D value between AD
      and AD/V patients. FA value reduced in the white matter of left inferior temporal
      gyrus and in the bilateral middle cingulate gyrus in patients with AD/V compared
      with controls. The MMSE (mini-mental state examination) score significantly
      correlated with FA value in the right hippocampus (r=0.639, P<0.019), in the
      right anterior cingulate gyrus (r=0.587, P<0.035) and in left parahippocampal
      gyrus (r=0.559, P<0.047). CONCLUSION: Cerebrovascular pathology had stronger
      impact on the D value than the AD pathology alone did. Elevated D value in
      thalamic and basal ganglia may contribute to cognitive decline in AD/V patients.
      Reduced FA values in AD/V patients may indicate that cerebrovascular pathology
      induced more severe white matter damage than the AD pathology alone did.

PMID- 17444599
TI  - Berbamine induces apoptosis in human hepatoma cell line SMMC7721 by loss in
      mitochondrial transmembrane potential and caspase activation.
AB  - OBJECTIVE: To investigate the effect of berbamine on human hepatoma cell line
      SMMC7721. METHODS: The effects of 24 h and 48 h incubation with different
      concentrations (0 to approximately 64 microg/ml) of the berbamine on SMMC7721
      cells were evaluated using 3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium
      bromide (MTT) assay. Hoechst 33258 staining was conducted to distinguish the
      apoptotic cell, and the appearance of sub-G1 stage was determined by PI
      (propidium iodide) staining, the percentage of apoptotic cell was determined by
      flow cytometry following annexin V/PI staining. Flow cytometry was performed to
      analyze the cell cycle distribution and the mitochondrial membrane potential
      (psi(m)); the expression of activated caspase3 and caspase9 was analyzed by
      Western-blot. RESULTS: The proliferation of SMMC7721 was decreased after
      treatment with berbamine in a dose- and time-dependent manner. Berbamine could
      induce apoptosis in SMMC7721 cells and could cause cell cycle arrest in G0/G1
      phase, to induce loss of mitochondrial membrane potential (psi(m)) and activate
      caspase3 and caspase9. Berbamine-induced apoptosis could be blocked by the broad
      caspase inhibitor z-VAD-fmk. CONCLUSION: Berbamine exerts antiproliferative
      effects on human hepatocellular carcinoma SMMC7721 cells. The anticancer activity
      of berbamine could be attributed partly to its inhibition of cell proliferation
      and induction of apoptosis in cancer cells through loss in mitochondrial
      transmembrane potential and caspase activation.

PMID- 17444600
TI  - A TOM1 homologue is required for multiplication of Tobacco mosaic virus in
      Nicotiana benthamiana.
AB  - The AtTOM1 gene of Arabidopsis thaliana had been shown to be essential for the
      efficient multiplication of Tobacco mosaic virus (TMV) in A. thaliana. In this
      study, we cloned an AtTOM1-like gene from Nicotiana benthamiana named as NbTOM1.
      Sequence alignment showed that NbTOM1 is closely related to AtTOM1 homologues of
      N. tabacum and Lycopersicon esculentum with 97.2% and 92.6% nucleotide sequence
      identities, respectively. Silencing of NbTOM1 by a modified viral satellite DNA
      based vector resulted in complete inhibition of the multiplication of TMV in N.
      benthamiana. The result suggests that inhibition of NbTOM1 via RNA silencing is a
      potentially useful method for generating TMV-resistant plants.

PMID- 17444601
TI  - Mrakia psychrophila sp. nov., a new species isolated from Antarctic soil.
AB  - The yeast strain (Y18) was isolated from a soil sample collected from Fildes
      Peninsula, Antarctica. The strain is a psychrophilic yeast with optimum and
      maximum growth temperatures of 10 degrees C and 18 degrees C, respectively.
      Teliospores were formed after 7 d on malt agar, when the germination of
      teliospores was observed. Both inositol and D-glucuronate were assimilated.
      Positive results of the DBB (diazonium blue B) color reaction, urease test, and
      starch formation were observed. The major CoQ is Q(8). All results indicated that
      Y18 belongs to the genes of Mrakia. The 18S rDNA sequence analyses showed that
      Y18 is closely related to Mrakia frigida. DNA-DNA relatedness study, and some
      biochemistry characteristics indicated that Y18 represents a new species for
      which Mrakia psychrophila sp. nov. is proposed.

PMID- 17444602
TI  - Synergistic interaction of NaCl and Cd on growth and photosynthetic parameters in
      soybean genotypes differing in salinity tolerance.
AB  - The effects of salinity (50 mmol/L NaCl) and Cd (1 micromol/L CdCl(2)) as sole
      and combined on growth and photosynthetic parameters were studied using two
      soybean genotypes, Huachun 18 and NGB. The concentrations of Cd(2+), Zn(2+),
      Ca(2+), Mg(2+), K(+) and Na(+) were also determined in seeds and pods. Huachun 18
      suffered a more serious decrease than NGB in net photosynthetic rate (P(n)) in
      the treatments of salinity stress alone and combined stress (NaCl+Cd), showing
      that it is relatively sensitive to salinity. The decrease in P(n) caused by salt
      stress in Huachun 18 was mainly due to the reduced total chlorophyll content and
      photosynthetic efficiency (the ratio of variable fluorescence to maximal
      fluorescence, F(v)/F(m)), whereas the decease in NGB was mainly related to
      reduced stomatal conductance (G(s)). The combined stress of both Na and Cd did
      not induce further decrease in photosynthesis and fluorescence in the two
      genotypes relative to salt or Cd stress alone. Greater change in the pod
      concentrations of Zn(2+), Ca(2+), Mg(2+), K(+) and Na(+) was detected under salt
      stress for Huachun 18 than for NGB. The results suggested that the interactive
      effect of NaCl-Cd on growth and nutrient uptake differs between the two soybean
      genotypes.

PMID- 17444603
TI  - Capillary gas chromatographic determination of dimethachlon residues in fresh
      tobacco leaves and cut-tobacco.
AB  - Simple procedures for extraction and chromatographic determination of
      dimethachlon residues in fresh tobacco leaves and cut-tobacco are described. The
      determination was carried out by capillary gas chromatography (GC) with electron
      capture detection (ECD) and confirmed by GC-MS. The mean recoveries and relative
      standard deviation (RSD) were 93.2%~112.9% and 3.5%~6.7%, respectively at levels
      ranging from 0.01 to 0.1 mg/kg. The limit of determination was 0.001 mg/kg.
      Tobacco samples in routine check were successfully analyzed using the proposed
      method.

PMID- 17444604
TI  - Protection of ultrastructure in chilling-stressed banana leaves by salicylic
      acid.
AB  - OBJECTIVE: Chilling tolerance of salicylic acid (SA) in banana seedlings (Musa
      acuminata cv., Williams 8818) was investigated by changes in ultrastructure in
      this study. METHODS: Light and electron microscope observation. RESULTS:
      Pretreatment with 0.5 mmol/L SA under normal growth conditions (30/22 degrees C)
      by foliar spray and root irrigation resulted in many changes in ultrastructure of
      banana cells, such as cells separation from palisade parenchymas, the appearance
      of crevices in cell walls, the swelling of grana and stromal thylakoids, and a
      reduction in the number of starch granules. These results implied that SA
      treatment at 30/22 degrees C could be a type of stress. During 3 d of exposure to
      7 degrees C chilling stress under low light, however, cell ultrastructure of SA
      pretreated banana seedlings showed less deterioration than those of control
      seedlings (distilled water-pretreated). CONCLUSION: SA could provide some
      protection for cell structure of chilling-stressed banana seedling.

PMID- 17444605
TI  - Changes in biochemical constituents and induction of early sprouting by
      triadimefon treatment in white yam (Dioscorea rotundata Poir.) tubers during
      storage.
AB  - The ability of triadimefon (TDM), a triazolic fungicide, to alter the biochemical
      constituents and thereby minimizing the days required for sprouting in white yam
      (Dioscorea rotundata Poir.) tubers during storage under (30+/-2) degrees C in the
      dark, was studied. TDM at 20 mg/L was given to tubers by dipping the tubers in
      treatment solution containing 20 mg/L TDM on 10, 25 and 40 d after storage (DAS).
      Starch, sugars, protein, amino acid contents as well as protease and alpha
      amylase activities were estimated on 15, 30 and 45 DAS from two physiological
      regions viz., apical and basal regions of the tubers. In normal conditions
      (control) sprouting occurred on 70 to 80 DAS. The starch content decreased, while
      protein, amino acid, sugar contents and protease and alpha-amylase activities
      were increased due to TDM treatment and led to early sprouting.

PMID- 17444606
TI  - Structural and mechanistic insights into methane oxidation by particulate methane
      monooxygenase.
AB  - Particulate methane monooxygense (pMMO) is an integral membrane copper-containing
      enzyme that converts methane to methanol. Knowledge of how pMMO selectively
      oxidizes methane under ambient conditions could impact the development of new
      catalysts. The crystal structure of Methylococcus capsulatus (Bath) pMMO reveals
      the composition and location of three metal centers. Spectroscopic data provide
      insight into the coordination environments and oxidation states of these metal
      centers. These results, combined with computational studies and comparisons to
      relevant systems, are discussed in the context of identifying the most likely
      site for O 2 activation.

PMID- 17444607
TI  - Radicals masquerading as electrophiles: dual orbital effects in nitrogen-philic
      acyl radical cyclization and related addition reactions.
AB  - Free-radical chemistry has come a long way in a relatively short period of time.
      The synthetic practitioner takes for granted the wealth of mechanistic and rate
      constant data now available and can apply free-radical techniques to the
      synthesis of many different classes of target molecule with confidence. Despite
      this, there are still mechanistic anomalies that need to be addressed. This
      Account highlights recent work involving nucleophilic radicals with low-lying
      unoccupied orbitals, such as acyl, oxyacyl, silyl, stannyl, and germyl radicals.
      Through interesting singly occupied molecular orbital (SOMO)-pi* and highest
      occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO)
      interactions during these reactions, the radicals involved are able to mask as
      electrophiles, providing high levels of regiocontrol and efficient methods for
      the synthesis of important heterocycles.

PMID- 17444609
TI  - Overcoming limiting side reactions associated with an NHS-activated precursor of
      polymethacrylamide-based polymers.
AB  - Combinatorial polymer libraries have recently gained popularity for the
      development of novel materials for a variety of biomedical applications including
      non-viral gene delivery systems and biodegradable polymers for tissue
      engineering. To streamline the nontrivial task of library synthesis, activated
      ester homopolymers have been used to serve as a backbone to which primary amine
      containing functional groups (NH2-FGs) can be covalently bound at varying ratios.
      Polymethacryloxysuccinimide (poly(MAOS)) is one such homopolymer that was
      previously reported to be an attractive precursor for polymeric drug and gene
      delivery systems. The reported functionalization protocols entailed conjugating
      the precursor with 2 equiv of the NH2-FG at a reaction concentration of 25 mg
      poly(MAOS)/150 microL DMSO for either 5 h at 50 degrees C or 16 h at 25 degrees
      C. More recently, both protocols were revealed to be associated with ring-opening
      and glutarimide-forming side reactions that compromise the utility of the
      homopolymer. Using 1-dimensional and 2-dimensional NMR spectroscopy techniques,
      we have characterized the side product distributions that result from
      conjugations performed at 50 degrees C/5 h and 25 degrees C/16 h. Moreover, by
      systematically altering the equivalents of the NH2-FGs, polymer concentration,
      reaction time, and reaction temperature, we have established a protocol that
      overcomes these side reactions. Using a final reaction protocol of 5 equiv of the
      NH2-FG at a reaction concentration of 25 mg poly(MAOS)/600 microL DMSO for 24 h
      at 75 degrees C, we have obtained functionalized polymers with minimal side
      products. This protocol is applicable for polymers ranging from 5000 to 50,000
      g/mol, compatible with a variety of functional groups, and amenable to
      conjugating combinations of functional groups.

PMID- 17444608
TI  - Fluorescent fructose derivatives for imaging breast cancer cells.
AB  - Breast cancer cells are known to overexpress Glut5, a sugar transporter
      responsible for the transfer of fructose across the cell membrane. Since Glut5
      transporter is not significantly expressed in normal breast cells, fructose
      uptake can potentially be used to differentiate between normal and cancerous
      cells. Fructose was labeled with two fluorophores at the C-1 position: 7-nitro
      1,2,3-benzadiazole (NBD) and Cy5.5. The labeling site was chosen on the basis of
      the presence and substrate specificity of the key proteins involved in the first
      steps of fructose metabolism. Using fluorescence microscopy, the uptake of the
      probes was studied in three breast cancer cell lines: MCF 7, MDA-MB-435, and MDA
      MB-231. Both fluorescent fructose derivatives showed a very good uptake in all
      tested cell lines. The level of uptake was comparable to that of the
      corresponding glucose analogs, 2-NBDG and Cy5.5-DG. Significant uptake of 1-NBDF
      derivative was not observed in cells lacking Glut5 transporter, while the uptake
      of the 1-Cy5.5-DF derivative was independent of the presence of a fructose
      specific transporter. While 1-NBDF showed Glut5-specific accumulation, the
      coupling of a large fluorophore such as Cy5.5 likely introduces big structural
      and electronic changes, leading to a fructose derivative that does not accurately
      describe the uptake of fructose in cells.

PMID- 17444610
TI  - Modification of trapping potential by inverted sidekick electrode voltage during
      detection to extend time-domain signal duration for significantly enhanced
      fourier transform ion cyclotron resonance mass resolution.
AB  - Applying an inverted voltage to the "sidekick" electrodes during ion cyclotron
      resonance detection improves both Fourier transform ion cyclotron resonance (FT
      ICR) mass spectral signal-to-noise ratio (at fixed resolving power) and resolving
      power (at fixed signal-to-noise ratio). The time-domain signal duration increases
      by up to a factor of 2. The method has been applied to 7-T FT-ICR MS of
      electrosprayed positive ions from substance P and human growth hormone protein (
      approximately 22 000 Da, m/Deltam50% 200 000), without the need for pulsed
      cooling gas inside the ICR trap. The modification can be easily adapted to any FT
      ICR instrument equipped with sidekick electrodes. The present effects are shown
      to be comparable to electron field modification by injection of an electron beam
      during ICR detection, reported by Kaiser and Bruce (Kaiser, N. K.; Bruce, J. E.
      Anal. Chem. 2005, 77, 5973-5981.). Although the exact mechanism is not fully
      understood, computer simulations show that a flattening of the radial potential
      gradient along the magnetic field direction in the ICR trap may contribute to the
      effects. This study not only provides a way to enhance the quality of FT-ICR mass
      spectra but also offers insight into understanding of ion motions inside an ICR
      ion trap.

PMID- 17444612
TI  - H2O2 sensor based on the room-temperature phosphorescence of Nano TiO2/SiO2
      composite.
AB  - A TiO2/SiO2 composite prepared by the sol-gel route can produce highly emissive
      broadband room-temperature phosphorescence at an excitation wavelength of 403 nm.
      The white phosphorescence of TiO2/SiO2 could be quenched by H2O2. The
      phosphorescence quenching effect demonstrated excellent sensitivity and high
      selectivity to H2O2. Furthermore, the phosphorescence of TiO2/SiO2 can be
      recovered when it is dipped in a hydroxylamine hydrochloride solution. Therefore,
      the TiO2/SiO2 was used to develop a reproducible phosphorescence sensor for H2O2.
      It has been successfully applied to the determination of H2O2 in the enzymatic
      catalytic reaction and real samples.

PMID- 17444611
TI  - Effect of cell size and shape on single-cell electroporation.
AB  - Single-cell electroporation was performed using electrolyte-filled capillaries on
      fluorescently labeled A549 cells. Cells were exposed to brief pulses (50-300 ms)
      at various cell-capillary tip distances. Cell viability and electroporation
      success were measured. In order to understand the variability in single-cell
      electroporation, logistic regression was used to determine whether the
      probabilities of cell survival and electroporation depend on experimental
      conditions and cell properties. Both experimental conditions and cell properties
      (size and shape) have a significant effect on the outcome. Finite element
      simulations were used to compare bulk electroporation to single-cell
      electroporation in terms of cell size and shape. Cells are more readily
      permeabilized and are more likely to survive if they are large and hemispherical
      as opposed to small and ellipsoidal with a high aspect ratio. The dependence of
      the maximum transmembrane potential across the cell membrane on cell size is much
      weaker than it is for bulk electroporation. Observed survival probabilities are
      related to the calculated fraction of the cell's surface area that is
      electroporated. Observed success of electroporation is related to the maximum
      transmembrane potential achieved.

PMID- 17444613
TI  - Dielectrophoretic manipulation of DNA: separation and polarizability.
AB  - Although separation of polymers based on the combination of dielectrophoretic
      trapping and electrophoretic forces was proposed 15 years ago, experimental proof
      has not yet been reported. Here, we address this problem for long DNA fragments
      in a simple and easy-to-fabricate microfluidic device, in which the DNA is
      manipulated by electrophoresis and by electrodeless dielectrophoresis. By slowly
      increasing the strength of the dielectrophoretic traps in the course of the
      separation experiments, we are able to perform efficient and fast DNA separation
      according to length for two different DNA conformations: linear DNA (lambda (48.5
      kbp) and T2 (164-kbp) DNA) and supercoiled covalently closed circular plasmid DNA
      (7 and 14 kbp). The underlying migration mechanism-thermally induced escape
      processes out of the dielectrophoretic traps in the direction of the
      electrophoretic force-is sensitive to different DNA fragments because of length
      dependent DNA polarizabilities. This is analyzed in a second series of
      experiments, where the migration mechanism is exploited for the quantitative
      measurement of the DNA polarizabilities. This new and simple technique allows for
      the systematic characterization of the polarizability not only for DNA but also
      for other biomolecules like proteins. Furthermore, our results have direct
      implications to future biotechnological applications such as gene therapy and DNA
      vaccination.

PMID- 17444614
TI  - Microfabricated monolithic multinozzle emitters for nanoelectrospray mass
      spectrometry.
AB  - Mass spectrometry is the enabling technology for proteomics. To fully realize the
      enormous potential of lab-on-a-chip in proteomics, a major advance in interfacing
      microfluidics with mass spectrometry is needed. Here, we report the first
      demonstration of monolithic integration of multinozzle electrospray emitters with
      a microfluidic channel via a novel silicon microfabrication process. These
      microfabricated monolithic multinozzle emitters (M3 emitters) can be readily mass
      produced from silicon wafers. Each emitter consists of a parallel silica nozzle
      array protruding out from a hollow silicon sliver with a conduit size of 100 x 10
      mum. The dimension and number of freestanding nozzles can be systematically and
      precisely controlled during the fabrication process. Once integrated with a mass
      spectrometer, M3 emitters achieved sensitivity and stability in peptide and
      protein detection comparable to those of commercial silica-based capillary
      nanoelectrospray tips. These M3 emitters may play a role as a critical component
      in a fully integrated silicon/silica-based micro total analysis system for
      proteomics.

PMID- 17444615
TI  - Enhancing Raman tweezers by phase-sensitive detection.
AB  - Raman spectroscopy has become a powerful tool for microscopic analysis of organic
      and biological materials. When combined with optical tweezers (Raman tweezers),
      it allows investigating single, selected micrometric particles in their natural
      environment, therefore, reducing unwanted interferences from the cover plate. A
      general problem affecting both Raman spectrometers and Raman tweezers systems is
      the background caused by the environment surrounding the sample under
      investigation. In this paper, we report on a novel method that allows acquiring
      Raman spectra of a single trapped particle (polystyrene microspheres) free from
      any background contribution. The method is based on the use of two collinear and
      copropagating laser beams: the first is devoted to trapping (trap laser), while
      the second one is used to excite the Raman transitions (pump laser). The trap
      laser moves the trapped particle periodically, by means of a galvomirror, back
      and forth across the pump laser. The back-scattered photons are analyzed by a
      spectrometer and detected by a photomultiplier; finally, the resulting signal is
      sent to a lock-in amplifier for phase-sensitive detection. The purpose of the
      present work is to give a detailed description of our method and to supply a
      systematic study concerning the formation of the Raman signal. We trap
      polystyrene beads and study the dependence of the Raman signal on several
      parameters, such as height from the coverslip surface, the bead size, the
      modulation amplitude, and the pump laser intensity. Our results establish a
      direct and practical approach for background suppression in the spectroscopic
      analysis of optical trapped microsized samples.

PMID- 17444616
TI  - Fundamental equation of dual-mode gradient elution in liquid chromatography
      involving simultaneous changes in flow rate and mobile-phase composition.
AB  - The rigorous derivation of the fundamental equation of the dual-mode gradient
      elution in liquid chromatography involving any type of simultaneous changes in
      flow rate and mobile-phase composition is developed following Drake's approach.
      The equation is a generalization of the already known fundamental equations of
      single gradient when either the mobile-phase composition or the flow rate is
      constant. The theory was tested in the retention prediction from isocratic data
      of 18 o-phthalaldehyde derivatives of amino acids in eluting systems modified by
      acetonitrile or methanol. The retention prediction obtained for all solutes under
      all dual-mode gradient conditions was excellent. The average percentage error
      between experimental and predicted retention times ranged from 0.9 to 2.5%. Two
      approximations that simplify the calculations considerably without increasing the
      above error were also proposed.

PMID- 17444617
TI  - Properties of nucleosomes in acetylated mouse mammary tumor virus versus 5S
      arrays.
AB  - Acetylation is one of the most abundant histone modifications found in
      nucleosomes. Although such modifications are thought to function mainly in
      recognition, acetylation is known to produce nucleosome structural alterations.
      These could be of functional significance in vivo. Here, the basic features of
      mouse mammary tumor virus (MMTV) promoter nucleosomal arrays reconstituted with
      highly acetylated histones prepared from butyrate-treated HeLa cells are
      characterized by atomic force microscopy. Results are compared to previous
      results obtained with hypoacetylated MMTV and hyper- or hypoacetylated 5S rDNA
      arrays. MMTV arrays containing highly acetylated histones show diminished
      intramolecular compaction compared to hypoacetylated MMTV arrays and no tendency
      for cooperativity in nucleosome occupation. Both features have been suggested to
      reflect histone tail-mediated internucleosomal interactions; these observations
      are consistent with that suggestion. 5S arrays show qualitatively similar
      behavior. Two other effects of acetylation show stronger DNA template dependence.
      Nucleosome salt stability is diminished in highly acetylated compared to
      hypoacetylated MMTV arrays, but nucleosome (histone) loading tendencies are
      unaffected by acetylation. However, highly acetylated histones show reduced
      loading tendencies on 5S templates (vs hypoacetylated), but 5S nucleosome salt
      stabilities are unaffected by acetylation. ATP-dependent nucleosome remodeling by
      human Swi-Snf is similar on hyper- and hypoacetylated MMTV arrays.

PMID- 17444618
TI  - Differential structural properties of GLP-1 and exendin-4 determine their
      relative affinity for the GLP-1 receptor N-terminal extracellular domain.
AB  - Glucagon-like peptide-1 (GLP-1) and exendin-4 (Ex4) are homologous peptides with
      established potential for treatment of type 2 diabetes. They bind and activate
      the pancreatic GLP-1 receptor (GLP-1R) with similar affinity and potency and
      thereby promote insulin secretion in a glucose-dependent manner. GLP-1R belongs
      to family B of the seven transmembrane G-protein coupled receptors. The N
      terminal extracellular domain (nGLP-1R) is a ligand binding domain with
      differential affinity for Ex4 and GLP-1: low affinity for GLP-1 and high affinity
      for exendin-4. The superior affinity of nGLP-1R for Ex4 was previously explained
      by an additional interaction between nGLP-1R and the C-terminal Trp-cage of Ex4.
      In this study we have combined biophysical and pharmacological approaches thus
      relating structural properties of the ligands in solution to their relative
      binding affinity for nGLP-1R. We used both a tracer competition assay and ligand
      induced thermal stabilization of nGLP-1R to measure the relative affinity of full
      length, truncated, and chimeric ligands for soluble refolded nGLP-1R. The ligands
      in solution and the conformational consequences of ligand binding to nGLP-1R were
      characterized by circular dichroism and fluorescence spectroscopy. We found a
      correlation between the helical content of the free ligands and their relative
      binding affinity for nGLP-1R, supporting the hypothesis that the ligands are
      helical at least in the segment that binds to nGLP-1R. The Trp-cage of Ex4 was
      not necessary to maintain a superior helicity of Ex4 compared to GLP-1. The
      results suggest that the differential affinity of nGLP-1R is explained almost
      entirely by divergent residues in the central part of the ligands: Leu10-Gly30 of
      Ex4 and Val16-Arg36 of GLP-1. In view of our results it appears that the Trp-cage
      plays only a minor role for the interaction between Ex4 and nGLP-1R and for the
      differential affinity of nGLP-1R for GLP-1 and Ex4.

PMID- 17444619
TI  - Local electronic structure of olivine phases of LixFePO4.
AB  - Changes in the local electronic structure at atoms around Li sites in the olivine
      phase of LiFePO4 were studied during delithiation. Electron energy loss
      spectrometry was used for measuring shifts and intensities of the near-edge
      structure at the K-edge of O and at the L-edges of P and Fe. Electronic structure
      calculations were performed on these materials with a plane-wave pseudopotential
      code and with an atomic multiplet code with crystal fields. It is found that both
      Fe and O atoms accommodate some of the charge around the Li+ ion, evidently in a
      hybridized Fe-O state. The O 2p levels appear to be fully occupied at the
      composition LiFePO4. With delithiation, however, these states are partially
      emptied, suggestive of a more covalent bonding to the oxygen atom in FePO4 as
      compared to LiFePO4. The same behavior is found for the white lines at the Fe
      L2,3-edges, which also undergo a shift in energy upon delithiation. A charge
      transfer of up to 0.48 electrons is found at the Fe atoms, as determined from
      white line intensity variations after delithiation, while the remaining charge is
      compensated by O atoms. No changes are evident at the P L2,3-edges.

PMID- 17444620
TI  - Experimental and theoretical study of the structure and reactivity of Fe1-2O< or
      =6- clusters with CO.
AB  - Synergistic studies employing experiments in the gas phase and theoretical first
      principles calculations have been carried out to investigate the structure,
      stability, and reactivity toward CO of iron oxide cluster anions, Fe(x)O(y)- (x =
      1-2, y < or = 6). Collision-induced dissociation studies of iron oxide species,
      employing xenon collision gas, show that FeO3- and FeO2- are the stable building
      blocks of the larger iron oxide clusters. Theoretical calculations show that the
      fragmentation patterns leading to the production of O or FeO(n) fragments are
      governed both by the energetics of the overall process as well as the number of
      intermediate states and the changes in spin multiplicity. Mass-selected
      experiments identified oxygen atom transfer to CO as the dominant reaction
      pathway for most anionic iron oxide clusters. A theoretical analysis of the
      molecular level pathways has been carried out to highlight the role of energetics
      as well as the spin states of the intermediates on the oxidation reaction.

PMID- 17444621
TI  - Reliable predictions of the thermochemistry of boron-nitrogen hydrogen storage
      compounds: BxNxHy, x = 2, 3.
AB  - Thermochemical data calculated using ab initio molecular orbital theory are
      reported for 16 BxNxHy compounds with x = 2, 3 and y > or = 2x. Accurate gas
      phase heats of formation were obtained using coupled cluster with single and
      double excitations and perturbative triples (CCSD(T)) valence electron
      calculations extrapolated to the complete basis set (CBS) limit with additional
      corrections including core/valence, scalar relativistic, and spin-orbit
      corrections to predict the atomization energies and scaled harmonic frequencies
      to correct for zero point and thermal energies and estimate entropies.
      Computationally cheaper calculations were also performed using the G3MP2 and G3B3
      variants of the Gaussian 03 method, as well as density functional theory (DFT)
      using the B3LYP functional. The G3MP2 heats of formation are too positive by up
      to approximately 6 kcal/mol as compared with CCSD(T)/CBS values. The more
      expensive G3B3 method predicts heats of formation that are too negative as
      compared with the CCSD(T)/CBS values by up to 3-4 kcal/mol. DFT using the B3LYP
      functional and 6-311+G** basis set predict isodesmic reaction energies to within
      a few kcal/mol compared with the CCSD(T)/CBS method so isodesmic reactions
      involving BN compounds and the analogous hydrocarbons can be used to estimate
      heats of formation. Heats of formation of c-B3N3H12 and c-B3N3H6 are -95.5 and 
      115.5 kcal/mol at 298 K, respectively, using our best calculated CCSD(T)/CBS
      approach. The experimental value for c-B3N3H6 appears to be approximately 7
      kcal/mol too negative. Enthalpies, entropies, and free energies are calculated
      for many dehydrocoupling and dehydrogenation reactions that convert BNH6 to
      alicyclic and cyclic oligomers and H2(g). Generally, the reactions are highly
      exothermic and exergonic as well because of the release of 1 or more equivalents
      of H2(g). For c-B3N3H12 and c-B3N3H6, available experimental data for sublimation
      and vaporization lead to estimates of their condensed phase 298 K heats of
      formation: DeltaHf degrees [c-B3N3H12(s)] = -124 kcal/mol and DeltaHf degrees [c
      B3N3H6(l)] = -123 kcal/mol. The reaction thermochemistries for the
      dehydrocoupling of BNH6(s) to c-B3N3H12(s) and the dehydrogenation of c
      B3N3H12(s) to c-B3N3H6(l) are much less exothermic compared with the gas-phase
      reactions due to intermolecular forces which decrease in the order BNH6 > cyclo
      B3N3H12 > cyclo-B3N3H6. The condensed phase reaction free energies are less
      negative compared with the gas-phase reactions but are still too favorable for
      BNH6 to be regenerated from either c-B3N3H12 or c-B3N3H6 by just an overpressure
      of H2.

PMID- 17444622
TI  - Renner-Teller bending frequencies of the approximately A 2Pi state of OCS+.
AB  - There are inconsistencies among previously reported Renner-Teller bending
      frequencies for the approximately A 2Pi state of OCS+. To resolve these
      controversies, we have computed vibrational frequencies using high-level excited
      electronic state ab initio equation-of-motion coupled cluster methods. On the
      basis of equation-of-motion coupled cluster theory including single, double, and
      iterative inclusion of partial triple excitations (EOM-CC3) paired with the
      correlation-consistent polarized valence quadruple-zeta basis set (cc-pVQZ), we
      predict harmonic bending frequencies of 364 and 401 cm-1 for the A' and A"
      components of approximately A 2Pi OCS+, respectively. Particularly for the upper
      Renner-Teller component, these results are lower than the theoretical predictions
      of 370 and 459 cm-1 reported by Chen, Hochlaf, Rosmus, He, and Ng [J. Chem. Phys.
      2002, 116, 5612]. Instead, the presently computed bending frequencies are more
      consistent with the experimentally derived average value of 357 +/- 5 cm-1
      recently reported by Sommavilla and Merkt [J. Phys. Chem. A 2004, 108, 9970],
      lending credence to the spectral assignments made in this later work. The two
      components of the Renner-Teller bending frequencies of approximately X 2Pi OCS+
      are similarly predicted to be 396 and 453 cm-1. Anharmonicity constants arising
      from a quartic force field computed at the cc-pVQZ EOM-CC3 level of theory are
      given, to provide a more complete characterization of the potential energy
      surface of the approximately A 2Pi state of OCS+.

PMID- 17444623
TI  - Discovery of the HCV NS3/4A protease inhibitor (1R,5S)-N-[3-amino-1
      (cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1
      dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3
      azabicyclo[3.1.0]hexan-2(S)-carboxamide (Sch 503034) II. Key steps in structure
      based optimization.
AB  - The structures of both the native holo-HCV NS3/4A protease domain and the
      protease domain with a serine 139 to alanine (S139A) mutation were solved to high
      resolution. Subsequently, structures were determined for a series of ketoamide
      inhibitors in complex with the protease. The changes in the inhibitor potency
      were correlated with changes in the buried surface area upon binding the
      inhibitor to the active site. The largest contribution to the binding energy
      arises from the hydrophobic interactions of the P1 and P2 groups as they bind to
      the S1 and S2 pockets [the numbering of the subsites is as defined in Berger, A.;
      Schechter, I. Philos. Trans. R. Soc. London, Ser. B 1970, 257, 249-264]. This
      correlation of the changes in potency with increased buried surface area
      contributed directly to the design of a potent tripeptide inhibitor of the HCV
      NS3/4A protease that is currently in clinical trials.

PMID- 17444624
TI  - Synthesis, DNA binding, and Leishmania topoisomerase inhibition activities of a
      novel series of anthra[1,2-d]imidazole-6,11-dione derivatives.
AB  - Nine novel anthra[1,2-d]imidazole-6,11-diones, differing in their side chain,
      were synthesized. UV-vis spectroscopy and viscometric titrations of these
      molecules with duplex DNA were used to assess their binding with DNA. Five of the
      nine compounds showed high inhibition activity against topoisomerase I of
      Leishmania donovani, with the one bearing the tetrazole side chain exhibiting an
      IC50 approximately 1 microM. The inhibition activities were not related with
      their DNA binding affinity and depended on the nature of the side chain.

PMID- 17444625
TI  - Design, synthesis, and in vitro gene delivery efficacies of novel cholesterol
      based gemini cationic lipids and their serum compatibility: a structure-activity
      investigation.
AB  - Five cholesterol-based gemini cationic lipids, which differ in the length of the
      spacer [-(CH2)n-] chain between the head groups, have been synthesized. These
      lipids are useful as nonviral gene delivery agents, and all cholesterol-based
      gemini lipids (2a-2e) are better transfecting agents than their monomeric lipid
      counterpart 1. Transfection efficiency of all the gemini lipids except lipid 2a [
      (CH2)3-] was maintained even when the serum was present during the transfection
      conditions as compared to the monomeric lipid 1, with which a dramatic decrease
      in transfection efficiency was observed. With the increase in spacer chain length
      from propanediyl [-(CH2)3-] to pentanediyl [-(CH2)5-], transfection efficiency
      increased both in the absence and presence of serum. However, transfection
      efficiency decreased with further increase in the length from the pentanediyl [
      (CH2)5-] to the dodecanediyl [-(CH2)12-] spacer. Among these gemini lipids 2c
      showed the highest transfection activity, which was also greater than that of the
      commercially available formulation.

PMID- 17444626
TI  - Design and synthesis of novel quinolinone-3-aminoamides and their alpha-lipoic
      acid adducts as antioxidant and anti-inflammatory agents.
AB  - A series of N-substituted-quinolinone-3-aminoamides and their hybrids containing
      the alpha-lipoic acid functionality were designed and synthesized as potential
      bifunctional agents combining antioxidant and anti-inflammatory activity. The new
      compounds were evaluated for their antioxidant activity and for their ability to
      inhibit in vitro lipoxygenase as well as for their anti-inflammatory activity in
      vivo. In general, the derivatives were found to be potent antioxidant or anti
      inflammatory agents. The results are discussed in terms of structure-activity
      relationships and an attempt is made to define the structural features required
      for activity.

PMID- 17444627
TI  - Structure-guided optimization of small molecules inhibiting human
      immunodeficiency virus 1 Tat association with the human coactivator p300/CREB
      binding protein-associated factor.
AB  - Human immunodeficiency virus 1 (HIV-1) trans-activator Tat recruits the human
      transcriptional coactivator PCAF (p300/CREB binding protein-associated factor) to
      facilitate transcription of the integrated HIV-1 provirus. We report here
      structure-based lead optimization of small-molecule inhibitors that block
      selectively Tat and PCAF association in cells. Our lead optimization was guided
      by grand-canonical ensemble simulation of the receptor/lead complex that leads to
      definition of chemical modifications with improved lead affinity through
      displacing weakly bound water molecules at the ligand-receptor interface.

PMID- 17444628
TI  - Long-distance structural consequences of H-bonding. How H-bonding affects
      aromaticity of the ring in variously substituted aniline/anilinium/anilide
      complexes with bases and acids.
AB  - The aromaticity of the ring in variously substituted aniline/anilinium/anilide
      derivatives in their H-bonded complexes with various Broensted acids and bases
      was a subject of an analysis based on 332 experimental geometries retrieved from
      the Cambridge Structural Database and geometries optimized at the B3LYP/6-311+G**
      and MP2/aug-cc-pVDZ levels of theory. Ab initio modeling was applied to the para
      substituted aniline, anilinium cation, and anilide anion derivatives (X = NO,
      NO2, CN, CHO, H, CH3, OCH3, and OH) and their H-bonded complexes (only for X =
      NO, NO2, CHO, H, and OH) with B (B = F- and CN-) or HB (HB = HF and HCN). In both
      cases, the harmonic oscillator model of aromaticity index (HOMA) was used,
      whereas for computational geometries, additionally, the magnetism-based indices
      NICS, NICS(1), and NICS(1)zz were also applied (NICS = nucleus-independent
      chemical shift). There is an equivalent prediction of aromaticity by NICSs and
      HOMA and approximate monotonic dependences of HOMA and NICS on the C-N bond
      length. The strongest changes in aromaticity estimated by HOMA and NICSs were
      found for aniline derivatives with NH2...B and anilide derivatives without and
      with NH-...HB interactions. The changes observed for two other kinds of
      interactions, NH2...HB and NH3+...base (for anilinium cations), are much smaller.
      For all four kinds of interactions, the relationships between ipso-bond angle,
      mean ipso-ortho bond length, and C-N bond length follow the Bent-Walsh rule.

PMID- 17444629
TI  - Mathematical correction for fingerprint similarity measures to improve chemical
      retrieval.
AB  - In many modern chemoinformatics systems, molecules are represented by long binary
      fingerprint vectors recording the presence or absence of particular features or
      substructures, such as labeled paths or trees, in the molecular graphs. These
      long fingerprints are often compressed to much shorter fingerprints using a
      simple modulo operation. As the length of the fingerprints decreases, their
      typical density and overlap tend to increase, and so does any similarity measure
      based on overlap, such as the widely used Tanimoto similarity. Here we show that
      this correlation between shorter fingerprints and higher similarity can be
      thought of as a systematic error introduced by the fingerprint folding algorithm
      and that this systematic error can be corrected mathematically. More precisely,
      given two molecules and their compressed fingerprints of a given length, we show
      how a better estimate of their uncompressed overlap, hence of their similarity,
      can be derived to correct for this bias. We show how the correction can be
      implemented not only for the Tanimoto measure but also for all other commonly
      used measures. Experiments on various data sets and fingerprint sizes demonstrate
      how, with a negligible computational overhead, the correction noticeably improves
      the sensitivity and specificity of chemical retrieval.

PMID- 17444630
TI  - Further insights into the spectroscopic properties, electronic structure, and
      kinetics of formation of the heme-peroxo-copper complex [(F8TPP)FeIII-(O2(2-)
      CuII(TMPA)]+.
AB  - In the further development and understanding of heme-copper O2-reduction
      chemistry inspired by the active-site chemistry in cytochrome c oxidase, we
      describe a dioxygen adduct, [(F8TPP)FeIII-(O22-)-CuII(TMPA)](ClO4) (3), formed by
      addition of O2 to a 1:1 mixture of the porphyrinate-iron(II) complex (F8TPP)FeII
      (1a) {F8TPP = tetrakis(2,6-difluorophenyl)porphyrinate dianion} and the copper(I)
      complex [(TMPA)CuI(MeCN)](ClO4) (1b) {TMPA = tris(2-pyridylmethyl)amine}. Complex
      3 forms in preference to heme-only or copper-only binuclear products, is
      remarkably stable {t1/2 (RT; MeCN) approximately 20 min; lambda max = 412
      (Soret), 558 nm; EPR silent}, and is formulated as a peroxo complex on the basis
      of manometry {1a/1b/O2 = 1:1:1}, MALDI-TOF mass spectrometry {16O2, m/z 1239 [(3
      + MeCN)+]; 18O2, m/z 1243}, and resonance Raman spectroscopy {nu(O-O) = 808 cm-1;
      Delta16O2/18O2 = 46 cm-1; Delta16O2/16/18O2 = 23 cm-1}. Consistent with a mu
      eta2:eta1 bridging peroxide ligand, two metal-O stretching frequencies are
      observed {nu(Fe-O) = 533 cm-1, nu(Fe-O-Cu) = 511 cm-1}, and supporting normal
      coordinate analysis is presented. 2H and 19F NMR spectroscopies reveal that 3 is
      high-spin {also muB = 5.1 +/- 0.2, Evans method} with downfield-shifted pyrrole
      and upfield-shifted TMPA resonances, similar to the pattern observed for the
      structurally characterized mu-oxo complex [(F8TPP)FeIII-O-CuII(TMPA)]+ (4) (known
      S = 2 system, antiferromagnetically coupled high-spin FeIII and CuII). Mossbauer
      spectroscopy exhibits a sharp quadrupole doublet (zero field; delta = 0.57 mm/s,
      |DeltaEQ| = 1.14 mm/s) for 3, with isomer shift and magnetic field dependence
      data indicative of a peroxide ligand and S = 2 formulation. Both UV-visible
      monitored stopped-flow kinetics and Mossbauer spectroscopic studies reveal the
      formation of heme-only superoxide complex (S)(F8TPP)FeIII-(O2-) (2a) (S = solvent
      molecule) prior to 3. Thermal decomposition of mu-peroxo complex 3 yields mu-oxo
      complex 4 with concomitant release of approximately 0.5 mol O2 per mol 3.
      Characterization of the reaction 1a/1b + O2 --> 2 --> 3 --> 4, presented here,
      advances our understanding and provides new insights to heme/Cu dioxygen-binding
      and reduction.

PMID- 17444631
TI  - Phosphinic platinum complexes with 8-thiotheophylline derivatives: synthesis,
      characterization, and antiproliferative activity.
AB  - The platinum mixed-phosphine complexes (SP-4,2)-[PtCl(8-MTT)(PPh3)(PTA)] (2) and
      cis-[Pt(8-MTT)2(PPh3)(PTA)] (3) (MTTH2 = 8-(methylthio)theophylline, PTA = 1,3,5
      triaza-7-phosphaadamantane) have been prepared from the precursor cis
      [PtCl2(PPh3)(PTA)] (1), which has been fully characterized by X-ray diffraction
      determination. Antiproliferative activity tests indicated that the presence of
      one lipophilic PPh3 and one hydrophilic PTA makes 1-3 more active than the
      analogues bearing two PPh3 or two PTA. The reactivity of cis-[PtCl2(PPh3)2], cis
      [PtCl2(PTA)2], and cis-[PtCl2(PPh3)(PTA)] with the bis(thiopurines) bis(S-8
      thiotheophylline)methane (MBTTH2), 1,2-bis(S-8-thiotheophylline)ethane (EBTTH2),
      and 1,3-bis(S-8-thiotheophylline)propane (PBTTH2) has also been investigated. New
      binuclear complexes have been prepared and identified by spectroscopic techniques
      and their antiproliferative activities on T2 and SKOV3 cell lines evaluated.

PMID- 17444632
TI  - Lanthanide compounds with fluorinated OC6F5 ligands: homo- and heterovalent
      complexes of Eu(II) and Eu(III).
AB  - The fluorinated phenoxide OC6F5 forms the stable Eu(II) and Eu(III) derivatives
      (DME)2Eu(mu-OC6F5)3Eu(mu-OC6F5)3Eu(DME)2 and (DME)2Eu(OC6F5)3, as well as the
      heterovalent product (DME)2Eu(mu-OC6F5)3Eu(DME)(OC6F5)2, in redox reactions of Eu
      with HOC6F5 or in proton-transfer reactions of HOC6F5 with Eu(SPh)2. The divalent
      complex crystallizes as a trimer with three bridging phenoxides bridging each
      pair of metals, with the terminal metals coordinating DME and the central metal
      ion encapsulated totally by O(C6F5) and dative fluoride interactions. The
      trivalent compound is monomeric with terminal phenoxide ligands and no Eu-F
      interactions. The heterovalent compound has clearly localized metal valence
      states and coordination features that mimic the homovalent species with the
      terminal OC6F5 bound to the Eu(III) ion, three bridging OR ligands spanning the
      Eu(II) and Eu(III) ions, and dative Eu(II)-F bonds. At elevated temperatures,
      these compounds decompose to give a mixture of solid-state fluoride phases.

PMID- 17444633
TI  - Heterobimetallic molecular cages for the deposition of Cu/Ti and Cu/Zn mixed
      metal oxides.
AB  - Heterobimetallic molecular precursors [Ti4(dmae)6(mu-OH)(mu-O)6Cu6(OAc)9.H2O] (1)
      and [Zn7(OAc)10(mu-OH)6Cu5(dmae)4Cl4] (2) for the deposition of metal oxide thin
      films of Cu6Ti4O12 (Cu3TiO4, TiO2) and Cu5Zn7O12 (ZnO, CuO) were prepared by the
      interaction of Ti(dmae)4 with Cu(OAc)2.2H2O for 1 and tetrameric (N,N
      dimethylamino)ethanolatocopper(II) chloride, [(dmae)CuCl]4 [where dmae = (N,N
      dimethylamino)ethanolate] with Zn(OAc)2.2H2O (where OAc = acetate) for 2 in dry
      toluene. Both complexes were characterized by melting point, elemental analysis,
      Fourier transform IR, fast atom bombardment mass spectrometry, thermal analysis
      (TGA), and single-crystal X-ray diffraction. TGA and XRD prove that complexes 1
      and 2 undergo facile thermal decomposition at 300 and 460 degrees C to form thin
      films of Cu/Ti and Cu/Zn mixed-metal oxides, respectively. Scanning electron
      microscopy and XRD of the thin films suggest the formation of impurity-free
      crystallite mixtures of Cu3TiO4 and TiO2, with average crystallite sizes of 22.2
      nm from complex 1 and of ZnO and CuO with average crystallite sizes of 26.1 nm
      from complex 2.

PMID- 17444634
TI  - A large [Mn10Na]4 loop of four linked Mn10 loops.
AB  - A large [Mn10Na]4 loop-of-loops aggregate was prepared from the use of 1,3
      propanediol (pdH2) in manganese carboxylate chemistry. It is constructed from
      four [Mn10(mu3-O)2(O2CMe)13(pd)6(py)2]- loops linked through Na+ ions and
      exhibits a saddlelike topology. Magnetic characterization showed that the Mn10
      loop has an S approximately 4 ground-state spin and displays frequency-dependent
      in-phase and out-of-phase alternating current signals and also hysteresis loops
      that, however, are not typical of single-molecule magnets because of the
      existence of intermolecular interactions between the Mn10 units.

PMID- 17444635
TI  - Studies directed to understanding the structure of chitosan-metal complexes:
      investigations of mono- and disaccharide models with platinum(II) group metals.
AB  - X-ray and NMR experiments were performed with simple chitosan models based on
      glucosamine monosaccharides and disaccharides to understand the binding
      properties and structures of the complexes formed between this polysaccharide and
      platinum(II) metals. Subjection of the glucosamine derivatives with
      [PdCl2(PhCN)2] provided trans-diamine complexes which upon further treatment with
      excess (NH4)PF6 generated complexes possessing two 5-membered chelate rings
      involving the C2-amine and the C3-hydroxyl group of the two individual
      glucosamine units.

PMID- 17444636
TI  - Tetrakis(thiadiazole)porphyrazines. 5. Electrochemical and DFT/TDDFT studies of
      the free-base macrocycle and its MgII, ZnII, and CuII complexes.
AB  - The redox properties of the phthalocyanine-like
      tetrakis(thiadiazole)porphyrazines, [TTDPzM] (M = MgII(H2O), ZnII, CuII, 2HI),
      were investigated by cyclic voltammetry, and their ground- and excited-state
      electronic properties were studied in detail by density functional theory (DFT)
      and time-dependent DFT (TDDFT) methods. Bulk and specific (axial ligation)
      solvent effects on the molecular and electronic structure were also taken into
      account. The title compounds show stepwise reversible ligand-centered one
      electron reductions in the range 0 to -2.0 V vs SCE, with E1/2 values being
      systematically less negative than corresponding reduction potentials for the same
      processes of the phthalocyanine (Pc) analogues. No electroxidations were observed
      at positive potentials. The observed redox behavior is rationalized on the basis
      of the ground-state electronic structures which reveal that replacement of the
      benzo rings of the Pc macrocycle by electron-withdrawing thiadiazole rings
      induces a large stabilization of both the HOMO and LUMOs in the investigated
      macrocycles. An excellent correlation is found between the first one-electron
      reduction potentials and the gas-phase LUMO energies along the series. The same
      sequence in the first reduction potentials is theoretically reproduced in
      pyridine, even if the ZnII and MgII complexes are assumed to be in the axially
      ligated form, [TTDPzM(py)]. TDDFT calculations of the lowest excited states of
      the ZnII, MgII, and CuII complexes in pyridine provide an accurate description of
      their UV-visible spectra. The calculated optical spectra for the free-base
      macrocycle in chlorobenzene and pyridine confirm previous data in that the
      thiadiazoleporphyrazine [TTDPzH2] is mostly present in pyridine in its
      deprotonated form [TTDPz]2-. DFT results, in keeping with electrochemical data,
      indicate, however, that in pyridine it is the neutral species [TTDPzH2] being
      reduced instead of its deprotonated form [TTDPz]2-.

PMID- 17444637
TI  - Three novel phases in the Sm-Co-Ga system. Syntheses, crystal and electronic
      structures, and electrical and magnetic properties.
AB  - This paper presents the synthesis, identification, and characterization of three
      novel phases in the ternary system Sm-Co-Ga: SmCoGa5 (tP7, HoCoGa5 type,
      tetragonal P4/mmm, Z = 1, a = 4.2419(3) A, and c = 6.8559(5) A), Sm4Co3Ga16
      (tP23, tetragonal P4/mmm, Z = 1, a = 6.0620(5) A, and c = 11.1495(9) A), and
      SmCoGa4 (oC24, YNiAl4 type, orthorhombic Cmcm, Z = 4, a = 4.1246(6) A, b =
      15.608(2) A, and c = 6.4556(9) A). The structure of SmCoGa5 was obtained from a
      multiphase X-ray powder Rietveld refinement whereas the crystal structures of the
      other two phases were determined from single-crystal X-ray analysis. Electronic
      structures were calculated for all phases by first-principles DFT methods. The
      atomic arrangements and bonding are discussed on the basis of the partial anionic
      networks involving Co and Ga atoms, and a strong structural correlation is
      observed between SmCoGa5 and Sm4Co3Ga16. The latter, which displays paramagnetic
      behavior, has a resistivity of 4.2 microOmega.cm at 3 K and undergoes a
      superconducting transition at 2.8 K.

PMID- 17444638
TI  - 1,4,7,10-tetraazacyclododecane metal complexes as potent promoters of
      carboxyester hydrolysis under physiological conditions.
AB  - New 1,4,7,10-tetrazacyclododecane ([12]aneN4 or cyclen) ligands with different
      heterocyclic spacers (triazine and pyridine) of various lengths (bi- and
      tripyridine) or an azacrown pendant and their mono- and dinuclear Zn(II), Cu(II),
      and Ni(II) complexes have been synthesized and characterized. The pKa values of
      water molecules coordinated to the complexed metal ions were determined by
      potentiometric pH titrations and vary from 7.7 to 11.2, depending on the metal
      ion and ligand properties. The X-ray structure of [Zn2L2]mu-OH(ClO4)3.CH3CN.H2O
      shows each Zn(II) ion in a tetrahedral geometry, binding to three N atoms of
      cyclen (the average distance of Zn-N = 2.1 A) and having a mu-OH bridge at the
      apical site linking the two metal ions (the average distance of Zn-O- = 1.9 A).
      The distance between the Zn(II) ion and the fourth N atom is 2.6 A. All Zn(II)
      complexes promote the hydrolysis of 4-nitrophenyl acetate (NA) under
      physiological conditions, while those of Cu(II) and Ni(II) do not have a
      significant effect on the hydrolysis reaction. The kinetic studies in buffered
      solutions (0.05 M Tris, HEPES, or CHES, I = 0.1 M, NaCl) at 25 degrees C in the
      pH range of 6-11 under pseudo-first-order reaction conditions (excess of the
      metal complex) were analyzed by applying the method of initial rates. Comparison
      of the second-order pH-independent rate constants (kNA, M-1 s-1) for the
      mononuclear complexes ZnL1, ZnL3, and ZnL8, which are 0.39, 0.27, and 0.38,
      respectively, indicates that the heterocyclic moiety improves the rate of
      hydrolysis up to 4 times over the parent Zn([12]aneN4) complex (kNA = 0.09 M-1 s
      1). The reactive species is the Zn(II)-OH- complex, in which the Zn(II)-bound OH-
      acts as a nucleophile, which attacks intermolecularly the carbonyl group of the
      acetate ester. For dinuclear complexes Zn2L2, Zn2L4, Zn2L5, Zn2L6, and Zn2L7, the
      mechanism of the reaction is defined by the degree of cooperation between the
      metal centers, determined by the spacer length. For Zn2L7, having the longest
      triaryl spacer, the two metal centers act independently in the hydrolysis;
      therefore, the reaction rate is twice as high as the rate of the mononuclear
      analogue (kNA = 0.78 M-1 s-1). The complexes with a monoaryl spacer show
      saturation kinetics with the formation of a Michaelis-Menten adduct. Their
      hydrolysis rates are 40 times higher than that of the Zn[12]aneN4 system (kNA
      approximately 4 M-1 s-1). Zn2L6 is a hybrid between these two mechanisms; a clear
      saturation curve is not visible nor are the metal cores completely independent
      from one another. Some of the Zn(II) complexes show a higher hydrolytic activity
      under physiological conditions compared to other previously reported complexes of
      this type.

PMID- 17444639
TI  - Dinitrosyl iron complexes (DNICs) containing S/N/O ligation: transformation of
      Roussin's red ester into the neutral {Fe(NO)2}10 DNICs.
AB  - Addition of the Lewis base [OPh]- to the THF solution of Roussin's red ester
      [Fe(mu-SC6H4-o-NHCOPh)(NO)2]2 (1) and [Fe(mu-SC6H4-o-COOH)(NO)2]2 (2),
      respectively, yielded the EPR-active, anionic {Fe(NO)2}9, [(SC6H4-o
      NCOPh)Fe(NO)2]- (3) with the anionic [SC6H4-o-NCOPh]2- ligand bound to the
      {Fe(NO)2} core in a bidentate manner (S,N-bonded) and [(SC6H4-o-COO)Fe(NO)2]- (4)
      with the anionic [SC6H4-o-COO]2- ligand bound to the {Fe(NO)2} core in a
      bidentate manner (S,O-bonded), characterized by IR, UV-vis, EPR, and single
      crystal X-ray diffraction. In contrast to the bridged-thiolate cleavage yielding
      the neutral {Fe(NO)2}9, [(SC6H4-o-NHCOPh)(Im)Fe(NO)2] (Im=imidazole), by addition
      of 2 equiv of imidazole to complex 1 observed in the previous study, the addition
      of the stronger sigma-donating and pi-accepting PPh3 ligand triggered the
      reductive elimination of bridged thiolates of complex 1 to yield the neutral
      {Fe(NO)2}10, [(PPh3)2Fe(NO)2]. These results unambiguously illustrate one aspect
      of how the nucleophile L (L=imidazole, PPh3, [OPh]-) functions to control the
      reaction pathways (bridged-thiolate cleavage, reductive elimination, and
      deprotonation) upon the reaction of complex 1 and the nucleophile L. The EPR
      active, dimeric {Fe(NO)2}9 dinitrosyl iron complex (DNIC) [Fe(mu-SC7H4SN)(NO)2]2
      (6), with S and N atoms of the anionic [-SC7H4SN-]- (2-benzothiozolyl thiolate)
      ligands bound to two separate {Fe(NO)2}9 cores, was also synthesized from
      reaction of bis(2-benzothiozolyl) disulfide and [(NO)2Fe(PPh3)2]. A
      straightforward reaction of complex 6 and 4 equiv of [N3]- conducted in THF led
      to the anionic {Fe(NO)2}9, [(N3)2Fe(NO)2]- (7). Conclusively, the EPR-active,
      {Fe(NO)2}9 DNICs can be classified into the anionic {Fe(NO)2}9 DNICs with S/N/O
      ligation, the neutral {Fe(NO)2}9 DNIC with one thiolate and one neutral imidazole
      ligation, and the cationic {Fe(NO)2}9 DNICs with the neutral N-/P-containing
      coordinated ligands.

PMID- 17444640
TI  - Addition of Pt(PBut3) to osmium-tin cluster complexes.
AB  - The reactions of the osmium-tin cluster complexes Os3(CO)12(mu3-SnPh)Ph, 9, and
      Os4(CO)16(mu4-Sn), 10, with Pt(PBut3)2 have been investigated. Two products,
      PtOs3(CO)12(Ph)(PBut3)(mu3-SnPh), 11, and Pt2Os3(CO)12(mu2-Ph)(PBut3)2(mu3-SnPh),
      12, were obtained from the reaction of 9 with Pt(PBut3)2. These are mono- and bis
      Pt(PBut3) adducts of 9 formed by the addition of a Pt(PBut3) group to the Os-Os
      bond in 11 and the Os-Os bond and Os-C bond to the sigma-bonded phenyl group in
      12. A PBut3 derivative of 11, Os2(CO)8(mu3-SnPh)Os(CO)3(PBut3)Ph, 13, was
      obtained by treating 12 with PBut3. The reaction of 10 with Pt(PBut3)2 provided
      the bis-Pt(PBut3) adduct Os4(CO)16[Pt(PBut3)]2(mu4-Sn), 14, that was formed by
      the addition of a Pt(PBut3) group across the Os-Os bond of both Os2(CO)8 groups
      in 10. All four new compounds 11-14 were characterized by single-crystal X-ray
      diffraction analysis.

PMID- 17444641
TI  - Combined experimental and theoretical study on aromatic hydroxylation by
      mononuclear nonheme iron(IV)-oxo complexes.
AB  - The hydroxylation of aromatic compounds by mononuclear nonheme iron(IV)-oxo
      complexes, [FeIV(Bn-tpen)(O)]2+ (Bn-tpen=N-benzyl-N,N',N'-tris(2
      pyridylmethyl)ethane-1,2-diamine) and [FeIV(N4Py)(O)]2+ (N4Py=N,N-bis(2
      pyridylmethyl)-N-bis(2-pyridyl)methylamine), has been investigated by a combined
      experimental and theoretical approach. In the experimental work, we have
      performed kinetic studies of the oxidation of anthracene with nonheme iron(IV)
      oxo complexes generated in situ, thereby determining kinetic and thermodynamic
      parameters, a Hammett rho value, and a kinetic isotope effect (KIE) value. A
      large negative Hammett rho value of -3.9 and an inverse KIE value of 0.9 indicate
      that the iron-oxo group attacks the aromatic ring via an electrophilic pathway.
      By carrying out isotope labeling experiments, the oxygen in oxygenated products
      was found to derive from the nonheme iron(IV)-oxo species. In the theoretical
      work, we have conducted density functional theory (DFT) calculations on the
      hydroxylation of benzene by [FeIV(N4Py)(O)]2+. The calculations show that the
      reaction proceeds via two-state reactivity patterns on competing triplet and
      quintet spin states via an initial rate determining electrophilic substitution
      step. In analogy to heme iron(IV)-oxo catalysts, the ligand is noninnocent and
      actively participates in the reaction mechanism by reshuttling a proton from the
      ipso position to the oxo group. Calculated kinetic isotope effects of C6H6 versus
      C6D6 confirm an inverse isotope effect for the electrophilic substitution
      pathway. Based on the experimental and theoretical results, we have concluded
      that the aromatic ring oxidation by mononuclear nonheme iron(IV)-oxo complexes
      does not occur via a hydrogen atom abstraction mechanism but involves an initial
      electrophilic attack on the pi-system of the aromatic ring to produce a
      tetrahedral radical or cationic sigma-complex.

PMID- 17444642
TI  - Unexpected preference of the E. coli translation system for the ester bond during
      incorporation of backbone-elongated substrates.
AB  - There have been recent advances in the ribosomal synthesis of various molecules
      composed of nonnatural ribosomal substrates. However, the ribosome has strict
      limitations on substrates with elongated backbones. Here, we show an unexpected
      loophole in the E. coli translation system, based on a remarkable disparity in
      its selectivity for beta-amino/hydroxy acids. We challenged beta-hydroxypropionic
      acid (beta-HPA), which is less nucleophilic than beta-amino acids but free from
      protonation, to produce a new repertoire of ribosome-compatible but main-chain
      elongated substrates. PAGE analysis and mass-coupled S-tag assays of amber
      suppression experiments using yeast suppressor tRNAPheCUA confirmed the actual
      incorporation of beta-HPA into proteins/oligopeptides. We investigated the side
      chain effects of beta-HPA and found that the side chain at position alpha and R
      stereochemistry of the beta-substrate is preferred and even notably enhances the
      efficiency of incorporation as compared to the parent substrate. These results
      indicate that the E. coli translation machinery can utilize main-chain-elongated
      substrates if the pKa of the substrate is appropriately chosen.

PMID- 17444643
TI  - Lone pair-pi and pi-pi interactions play an important role in proton-coupled
      electron transfer reactions.
AB  - Proton-coupled electron transfer (PCET), a class of formal hydrogen atom transfer
      (HAT) reactions, is of widespread interest because it is implicated in a broad
      range of chemical and biochemical processes. PCET is typically differentiated
      from HAT by the fact that it occurs when a proton and electron are transferred
      between different sets of molecular orbitals. Previous theoretical work predicted
      that hydrogen bonding between reactants is a necessary but not sufficient
      condition for H exchanges to take place by PCET. This implies that HAT is the
      only mechanism for H exchange between two carbon atoms. In this work, we present
      computational results that show that the H exchange in the tert
      butylperoxyl/phenol couple, a prototypical antioxidant exchange reaction, occurs
      by PCET and that the transfer of the electron can occur via an oxygen lone pair
      ring pi overlap. We then show that the H exchange in a model for the
      tyrosyl/tyrosine couple, which is implicated in ribonucleotide reductase
      chemistry, occurs via PCET and that one path for the electron transfer is
      provided by a strong pi-stacking interaction. Finally, we show that a pi-stacking
      interaction in the benzyl/toluene couple, a system in which there is no H
      bonding, can result in this exchange occurring via PCET to some extent.
      Collectively, these results indicate that PCET reactions are not unique to
      systems that can engage in H-bonding and that lone pair-pi and pi-pi interactions
      in these systems may be more important than previously understood.

PMID- 17444644
TI  - Selective bond breaking in beta-D-ribose by gas-phase electron attachment around
      8 eV.
AB  - Electron attachment experiments are carried out on the beta-d-ribose molecule in
      the gas phase for the energy region around 8 eV, and clear fragmentation products
      are observed for different mass values. A computational analysis of the relevant
      dynamics is also carried out for the beta-d-ribose in both the furanosic and
      pyranosic form as gaseous targets around that energy range. The quantum
      scattering attributes obtained from the calculations reveal in both systems the
      presence of transient negative ions (TNIs). An analysis of the spatial features
      of the excess resonant electron, together with the computation and
      characterization of the target molecular normal modes, suggests possible break-up
      pathways of the initial, metastable molecular species.

PMID- 17444645
TI  - Field induced formation of mesoscopic polymer chains from functional
      ferromagnetic colloids.
AB  - The assembly and direct imaging of ferromagnetic nanoparticles into one
      dimensional mesostructures (1-D) are reported. Polymer-coated ferromagnetic
      colloids (19 nm, 24 nm) were assembled at a crosslinkable oil-water interface
      under both magnetic field induced and zero-field conditions and permanently fixed
      into 1-D mesoscopic polymer chains (1-9 mum) in a process referred to as
      Fossilized Liquid Assembly (FLA). In the FLA process, nanoparticle chains were
      fixed at the oil interface through photopolymerization, enabling direct
      visualization of organized mesostructures using atomic force microscopy. Using
      the FLA methodology, we systematically investigated different conditions and
      demonstrated that dispersed ferromagnetic colloids possess sufficient dipolar
      interactions to organize into mesoscopic assemblies. Application of an external
      magnetic field during assembly enabled the formation of micron-sized chains which
      were aligned in the direction of the applied field. This universal methodology is
      an attractive alternative technique to cryogenic transmission electron microscopy
      (cryo-TEM) for the visualization of nanoparticle assembly in dispersed organic
      media.

PMID- 17444646
TI  - Monomeric, two-coordinate, univalent chromium(I) compounds: steric prevention of
      metal-metal bond formation.

PMID- 17444647
TI  - Ruthenium-catalyzed carbon-carbon bond formation via the cleavage of an
      unreactive aryl carbon-nitrogen bond in aniline derivatives with organoboronates.

PMID- 17444648
TI  - New electrophilic difluoromethylating reagent.
AB  - A new electrophilic difluoromethylating reagent has been developed. The S
      (difluoromethyl)diarylsulfonium tetrafluoroborate has been shown to be effective
      for the introduction of an electrophilic difluoromethyl group into the following
      nucleophiles: sulfonic acids, tertiary amines, imidazole derivatives, and
      phosphines. The reagent failed to transfer the difluoromethyl group to phenols,
      carbon nucleophiles, and primary and secondary amines.

PMID- 17444650
TI  - Metallo supramolecular assemblies of bis-squaraines by allosteric Ca2+ ion
      binding.
AB  - Alkyl chain tethered bis-squaraines bind to Ca2+ ions through the participation
      of the negatively charged oxygen of the central cyclobutene moiety to form folded
      H-type aggregates. The initially formed Ca2+ complex is preorganized to
      facilitate cooperative allosteric binding of Ca2+, resulting in the formation of
      extended supramolecular arrays. The electronic absorption, IR, and ESI-MS studies
      support the formation of metallo supramolecular architectures of the folded H
      type dimers of the bis-squaraines.

PMID- 17444649
TI  - N-substituted imines by the copper-catalyzed N-imination of boronic acids and
      organostannanes with O-acyl ketoximes.
AB  - Catalytic quantities of copper(I) or copper(II) sources catalyze the N-imination
      of boronic acids and organostannanes through reaction with oxime O-carboxylates
      under nonbasic conditions. This method tolerates various functional groups and
      takes place efficiently using aryl, heteroaryl, and alkenyl boronic acids and
      stannanes.

PMID- 17444651
TI  - Hydrothermal reactions from sodium hydrogen carbonate to phenol.
AB  - We report here experimental evidence for the hydrothermal formation of a pure
      organic molecule, phenol, from the reaction of carbonate with water in the
      presence of iron powders.

PMID- 17444652
TI  - Qualitative and quantitative differences in carotenoid composition among
      Cucurbita moschata, Cucurbita maxima, and Cucurbita pepo.
AB  - Squashes and pumpkins are important dietary sources of carotenoids worldwide. The
      carotenoid composition has been determined, but reported data have been highly
      variable, both qualitatively and quantitatively. In the present work, the
      carotenoid composition of squashes and pumpkins currently marketed in Campinas,
      Brazil, were determined by HPLC-DAD, complemented by HPLC-MS for identification.
      Cucurbita moschata 'Menina Brasileira' and C. moschata 'Goianinha' had similar
      profiles, with beta-carotene and alpha-carotene as the major carotenoids. The
      hybrid 'Tetsukabuto' resembled the Cucurbita pepo 'Mogango', lutein and beta
      carotene being the principal carotenoids. Cucurbita maxima 'Exposicao' had a
      different profile, with the predominance of violaxanthin, followed by beta
      carotene and lutein. Combining data from the current study with those in the
      literature, profiles for the Cucurbita species could be observed. The principal
      carotenoids in C. moschata were beta-carotene and alpha-carotene, whlereas lutein
      and beta-carotene dominate in C. maxima and C. pepo. It appears that
      hydroxylation is a control point in carotenoid biosynthesis.

PMID- 17444653
TI  - A commercial extract of fruits and vegetables, Oxxynea, acts as a powerful
      antiatherosclerotic supplement in an animal model by reducing cholesterolemia,
      oxidative stress, and NADPH oxidase expression.
AB  - The effects of fruit and vegetable extract (Oxxynea) on plasma cholesterol, early
      atherosclerosis, cardiac production of superoxide anion, and NAD(P)H oxidase
      expression were studied in an animal model of atherosclerosis. Thirty six
      hamsters were divided into two groups of 18 and fed an atherogenic diet for 12
      weeks. They received by gavage either water or Oxxynea in water at a human dose
      equivalent of 10 fruits and vegetables per day. Oxxynea lowered plasma
      cholesterol and non-HDL cholesterol, but not HDL-cholesterol, and increased
      plasma antioxidant capacity. It also strongly reduced the area of aortic fatty
      streak deposition by 77%, cardiac production of superoxide anion by 45%, and
      p22phox subunit of NAD(P)H oxidase expression by 59%. These findings support the
      view that chronic consumption of antioxidants supplied by fruits and vegetables
      has potential beneficial effects with respect to the development of
      atherosclerosis. The underlying mechanism is related mainly to inhibiting pro
      oxidant factors and improving the serum lipid profile.

PMID- 17444654
TI  - Difructose anhydride III promotes absorption of the soluble flavonoid alphaG
      rutin in rats.
AB  - A highly soluble quercetin glycoside, alphaG-rutin, is a glucose adduct of
      insoluble rutin. We examined the effects of difructose anhydride III (DFAIII; di
      D-fructofuranosyl 1,2':2,3'-dianhydride) on intestinal absorption of alphaG-rutin
      by rat experiments. alphaG-rutin, rutin, quercetin, and the quercetin conjugate
      appeared in the portal blood after an intubation of alphaG-rutin (100 micromol),
      DFAIII effected higher portal concentrations of alphaG-rutin in portal cannulated
      rats. In ligated jejunal and ileal loops of rats, alphaG-rutin, rutin, quercetin,
      and the quercetin conjugate appeared in the intestinal mesenteric blood at both
      30 and 60 min in both loops; the concentration of alphaG-rutin was 1.5-3 times
      higher when absorbed in the presence DFAIII. In the isolated mucosae of the
      jejunum and ileum, mucosal-to-serosal passage of alphaG-rutin increased with the
      addition of 100 micromol of DFAIII. These results indicate that alphaG-rutin is
      absorbed as the intact form and that DFAIII stimulates its absorption in the
      small intestine.

PMID- 17444655
TI  - Identification and sensory evaluation of dehydro- and deoxy-ellagitannins formed
      upon toasting of oak wood (Quercus alba L.).
AB  - Traditionally, spirits such as whiskey are matured in toasted wood barrels to
      improve the sensory quality of the final beverage. In order to gain first insight
      into the puzzling road map of thermal ellagitannin transformation chemistry and
      provide evidence for the changes in sensory active nonvolatiles in oak wood
      during toasting, the purified oak ellagitannins castalagin and vescalagin, their
      corresponding dimers roburin A and roburin D, and 33-carboxy-33-deoxyvescalagin
      were thermally treated in model experiments. Besides mouth-coating and golden
      brown colored melanoidin-type polymers, individual major reaction products were
      produced as transient intermediates which were identified for the first time by
      means of LC-MS/MS and 1D/2D-NMR spectroscopy. Depending strongly on the
      stereochemistry, castalagin is oxidized to the previously unreported
      dehydrocastalagin, whereas its diastereomer vescalagin, differing only in the
      stereochemistry at carbon C-1, is most surprisingly converted into
      deoxyvescalagin. Comparative model experiments with 33-carboxy-33-deoxyvescalagin
      revealed castalagin, vescalagin, dehydrocastalagin, and deoxyvescalagin as
      typical reaction products, thus indicating decarboxylation as a key step in the
      thermal degradation of that ellagitannin. Similar to the ellagitannin monomers,
      LC-MS/MS analyses gave strong evidence that the corresponding dimer roburin A,
      containing the vescalagin configuration at C-1, was converted into the
      deoxyroburin A, whereas roburin D, exhibiting the castalagin configuration at C
      1, was oxidized to give the dehydroroburin D. Human sensory experiments revealed
      that the ellagitannin derivatives imparted an astringent mouth-coating sensation
      with threshold concentrations ranging from 1.1 to 126.0 micromol/L, depending
      strongly on their chemical structure.

PMID- 17444657
TI  - High cationic charge and bilayer interface-binding helices in a regulatory lipid
      glycosyltransferase.
AB  - In the prokaryote Acholeplasma laidlawii, membrane bilayer properties are sensed
      and regulated by two interface glycosyltransferases (GTs), synthesizing major
      nonbilayer- (alMGS GT) and bilayer-prone glucolipids. These enzymes are of
      similar structure, as many soluble GTs, but are sensitive to lipid charge and
      curvature stress properties. Multivariate and bioinformatic sequence analyses
      show that such interface enzymes, in relation to soluble ones of similar fold,
      are characterized by high cationic charge, certain distances between small and
      cationic amino acids, and by amphipathic helices. Varying surface contents of
      Lys/Arg pairs and Trp indicate different membrane-binding subclasses. A predicted
      potential (cationic) binding helix from alMGS was structurally verified by
      solution NMR and CD. The helix conformation was induced by a zwitterionic as well
      as anionic lipid environment, and the peptide was confined to the bilayer
      interface. Bilayer affinity of the peptide, analyzed by surface plasmon
      resonance, was higher than that for soluble membrane-seeking proteins/peptides
      and rose with anionic lipid content. Interface intercalation was supported by
      phase equilibria in membrane lipid mixtures, analyzed by 31P NMR and DSC. An
      analogous, potentially binding helix has a similar location in the structurally
      determined Escherichia coli cell wall precursor GT MurG. These two helices have
      little sequence conservation in alMGS and MurG homologues but maintain their
      amphipathic character. The evolutionary modification of the alMGS binding helix
      and its location close to the acceptor substrate site imply a functional
      importance in enzyme catalysis, potentially providing a mechanism by which
      glycolipid synthesis will be sensitive to membrane surface charge and intrinsic
      curvature strain.

PMID- 17444656
TI  - Site-specific S-glutathiolation of mitochondrial NADH ubiquinone reductase.
AB  - The generation of reactive oxygen species in mitochondria acts as a redox signal
      in triggering cellular events such as apoptosis, proliferation, and senescence.
      Overproduction of superoxide (O2*-) and O2*--derived oxidants changes the redox
      status of the mitochondrial GSH pool. An electron transport protein,
      mitochondrial complex I, is the major host of reactive/regulatory protein thiols.
      An important response of protein thiols to oxidative stress is to reversibly form
      protein mixed disulfide via S-glutathiolation. Exposure of complex I to oxidized
      GSH, GSSG, resulted in specific S-glutathiolation at the 51 kDa and 75 kDa
      subunits (Beer et al. (2004) J. Biol. Chem. 279, 47939-47951). Here, to
      investigate the molecular mechanism of S-glutathiolation of complex I, we
      prepared isolated bovine complex I under nonreducing conditions and employed the
      techniques of mass spectrometry and EPR spin trapping for analysis. LC/MS/MS
      analysis of tryptic digests of the 51 kDa and 75 kDa polypeptides from
      glutathiolated complex I (GS-NQR) revealed that two specific cysteines (C206 and
      C187) of the 51 kDa subunit and one specific cysteine (C367) of the 75 kDa
      subunit were involved in redox modifications with GS binding. The electron
      transfer activity (ETA) of GS-NQR in catalyzing NADH oxidation by Q1 was
      significantly enhanced. However, O2*- generation activity (SGA) mediated by GS
      NQR suffered a mild loss as measured by EPR spin trapping, suggesting the
      protective role of S-glutathiolation in the intact complex I. Exposure of NADH
      dehydrogenase (NDH), the flavin subcomplex of complex I, to GSSG resulted in
      specific S-glutathiolation on the 51 kDa subunit. Both ETA and SGA of S
      glutathiolated NDH (GS-NDH) decreased in parallel as the dosage of GSSG
      increased. LC/MS/MS analysis of a tryptic digest of the 51 kDa subunit from GS
      NDH revealed that C206, C187, and C425 were glutathiolated. C425 of the 51 kDa
      subunit is a ligand residue of the 4Fe-4S N3 center, suggesting that destruction
      of 4Fe-4S is the major mechanism involved in the inhibition of NDH. The result
      also implies that S-glutathiolation of the 75 kDa subunit may play a role in
      protecting the 4Fe-4S cluster of the 51 kDa subunit from redox modification when
      complex I is exposed to redox change in the GSH pool.

PMID- 17444658
TI  - Interaction of benzoate pyrimidine analogues with class 1A dihydroorotate
      dehydrogenase from Lactococcus lactis.
AB  - Dihydroorotate dehydrogenases (DHODs) catalyze the oxidation of dihydroorotate to
      orotate in the only redox reaction in pyrimidine biosynthesis. The pyrimidine
      binding sites are very similar in all structurally characterized DHODs,
      suggesting that the prospects for identifying a class-specific inhibitor directed
      against this site are poor. Nonetheless, two compounds that bind specifically to
      the Class 1A DHOD from Lactococcus lactis, 3,4-dihydroxybenzoate (3,4-diOHB) and
      3,5-dihydroxybenzoate (3,5-diOHB), have been identified [Palfey et al. (2001) J.
      Med. Chem. 44, 2861-2864]. The mechanism of inhibitor binding to the Class 1A
      DHOD from L. lactis has now been studied in detail and is reported here.
      Titrations showed that 3,4-diOHB binds more tightly at higher pH, whereas the
      opposite is true for 3,5-diOHB. Isothermal titration calorimetry and absorbance
      spectroscopy showed that 3,4-diOHB ionizes to the phenolate upon binding to the
      enzyme, but 3,5-diOHB does not. The charge-transfer band that forms in the 3,4
      diOHB complex allowed the kinetics of binding to be observed in stopped-flow
      experiments. Binding was slow enough to observe from pH 6 to pH 8 and was
      (minimally) a two-step process consisting of the rapid formation of a complex
      that isomerized to the final charge-transfer complex. Orotate and 3,5-diOHB bind
      too quickly to follow directly, but their dissociation kinetics were studied by
      competition and described adequately with a single step. Crystal structures of
      both inhibitor complexes were determined, showing that 3,5-diOHB binds in the
      same orientation as orotate. In contrast, 3,4-diOHB binds in a twisted
      orientation, enabling one of its phenolic oxygens to form a very strong hydrogen
      bond to an asparagine, thus stabilizing the phenolate and causing charge-transfer
      interactions with the pi-system of the flavin, resulting in a green color.

PMID- 17444659
TI  - Exploration of new chromophore structures leads to the identification of improved
      blue fluorescent proteins.
AB  - The variant of Aequorea green fluorescent protein (GFP) known as blue fluorescent
      protein (BFP) was originally engineered by substituting histidine for tyrosine in
      the chromophore precursor sequence. Herein we report improved versions of BFP
      along with a variety of engineered fluorescent protein variants with novel and
      distinct chromophore structures that all share the property of a blue fluorescent
      hue. The two most intriguing of the new variants are a version of GFP in which
      the chromophore does not undergo excited-state proton transfer and a version of
      mCherry with a phenylalanine-derived chromophore. All of the new blue fluorescing
      proteins have been critically assessed for their utility in live cell fluorescent
      imaging. These new variants should greatly facilitate multicolor fluorescent
      imaging by legitimizing blue fluorescing proteins as practical and robust members
      of the fluorescent protein "toolkit".

PMID- 17444660
TI  - Effects of oxidation on the structure and stability of human low-density
      lipoprotein.
AB  - Oxidation of low-density lipoprotein (LDL), the major cholesterol carrier in
      plasma, is thought to promote atherogenesis via several mechanisms. One proposed
      mechanism involves fusion of oxidized LDL in the arterial wall; another involves
      oxidation-induced amyloid formation by LDL apolipoprotein B. To test these
      mechanisms and to determine the effects of oxidation on the protein secondary
      structure and lipoprotein fusion in vitro, we analyzed LDL oxidized by
      nonenzymatic (Cu2+, H2O2, and HOCl) or enzymatic methods (myeloperoxidase/H2O2/Cl
      and myeloperoxidase/H2O2/NO2-). Far-UV circular dichroism spectra showed that
      LDL oxidation induces partial unfolding of the secondary structure rather than
      folding into cross-beta amyloid conformation. This unfolding correlates with
      increased negative charge of oxidized LDL and with a moderate increase in
      thioflavin T fluorescence that may result from electrostatic attraction between
      the cationic dye and electronegative LDL rather than from dye binding to amyloid.
      These and other spectroscopic studies of low- and high-density lipoproteins,
      which encompass amyloid-promoting conditions (high protein concentrations, high
      temperatures, acidic pH), demonstrate that in vitro lipoprotein oxidation does
      not induce amyloid formation. Surprisingly, turbidity, near-UV circular
      dichroism, and electron microscopic data demonstrate that advanced oxidation
      inhibits heat-induced LDL fusion that is characteristic of native lipoproteins.
      Such fusion inhibition may result from the accumulation of anionic lipids and
      lysophospholipids on the particle surface and/or from protein cross-linking upon
      advanced lipoprotein oxidation. Consequently, oxidation alone may prevent rather
      than promote LDL fusion, suggesting that additional factors, such as albumin
      mediated removal of lipid peroxidation products and/or LDL binding to arterial
      proteoglycans, facilitate fusion of oxidized LDL in vivo.

PMID- 17444662
TI  - Molecular-thermodynamic theory of micellization of multicomponent surfactant
      mixtures: 1. Conventional (pH-Insensitive) surfactants.
AB  - A molecular-thermodynamic (MT) theory was developed to model the micellization of
      mixtures containing an arbitrary number of conventional (pH-insensitive)
      surfactants. The theory was validated by comparing predicted and experimental
      cmc's of ternary surfactant mixtures, yielding results that were comparable to,
      and sometimes better than, the cmc's determined using regular solution theory.
      The theory was also used to model a commercial nonionic surfactant (Genapol UD
      079), which was modeled as a mixture of 16 surfactant components. The predicted
      cmc agreed well with the experimental cmc, and the monomer concentration was
      predicted to increase significantly above the cmc. In addition, the monomer and
      the micelle compositions were predicted to vary significantly with surfactant
      concentration. These composition variations were rationalized in terms of
      competing steric and entropic effects and a micelle shape transition near the
      cmc. To understand the packing constraints imposed on ternary surfactant mixtures
      better, the maximum micelle radius was also examined theoretically. The MT theory
      presented here represents the first molecular-based theory of the micellization
      behavior of mixtures of three or more conventional surfactants. In article 2 of
      this series, the MT theory will be extended to model the micellization of
      mixtures of conventional and pH-sensitive surfactants.

PMID- 17444663
TI  - Molecular-thermodynamic theory of micellization of multicomponent surfactant
      mixtures: 2. pH-sensitive surfactants.
AB  - In article 1 of this series, we developed a molecular-thermodynamic (MT) theory
      to model the micellization of mixtures containing an arbitrary number of
      conventional (pH-insensitive) surfactants. In this article, we extend the MT
      theory to model mixtures containing a pH-sensitive surfactant. The MT theory was
      validated by examining mixtures containing both a pH-sensitive surfactant and a
      conventional surfactant, which effectively behave like ternary surfactant
      mixtures. We first compared the predicted micellar titration data to experimental
      micellar titration data that we obtained for varying compositions of mixed
      micelles containing the pH-sensitive surfactant dodecyldimethylamine oxide
      (C12DAO) mixed with either a cationic surfactant (dodecyltrimethylammonium
      bromide, C12TAB), a nonionic surfactant (dodecyl octa(ethylene oxide), C12E8), or
      an anionic surfactant (sodium dodecyl sulfate, SDS) surfactant. The MT theory
      accurately modeled the titration behavior of C12DAO mixed with C12E8. However,
      C12DAO was observed to interact more favorably with SDS and with C12TAB than was
      predicted by the MT theory. We also compared predictions to data from the
      literature for mixtures of C12DAO and SDS. Although the pH values of solutions
      with no added acid were modeled with only qualitative accuracy, the MT theory
      resulted in quantitatively accurate predictions of solution pH for mixtures
      containing added acid. In addition, the predicted degree of counterion binding
      yielded a lower bound to the experimentally measured value. Finally, we predicted
      the critical micelle concentration (cmc) of solutions of two pH-sensitive
      surfactants, tetradecyldimethylamine oxide (C14DAO) and hexadecyldimethyl betaine
      (C16Bet), at varying solution pH and surfactant composition. However, at the pH
      values considered, the pH sensitivity of C16Bet could be neglected, and it was
      equivalently modeled as a zwitterionic surfactant. The cmc's predicted using the
      MT theory agreed well with the experimental cmc's and were found to be comparable
      to and sometimes better than the cmc's determined using the regular solution
      theory (RST), even though the empirical RST utilizes experimentally measured
      cmc's as an input. The MT theory presented here represents the first molecular
      based quantitative description of the micellization behavior of mixtures of pH
      sensitive surfactants and conventional surfactants, and allows qualitative and
      quantitative predictions of the micellization behavior of a variety of surfactant
      systems.

PMID- 17444664
TI  - Shape-gradient composite surfaces: water droplets move uphill.
AB  - The approach of water droplets self-running horizontally and uphill without any
      other forces was proposed by patterning the shape-gradient hydrophilic material
      (i.e., mica) to the hydrophobic matrix (i.e., wax or low-density polyethylene
      (LDPE)). The shape-gradient composite surface is the best one to drive water
      droplet self-running both at the high velocity and the maximal distance among
      four different geometrical mica/wax composite surfaces. The driving force for the
      water droplets self-running includes: (1) the great difference in wettability of
      surface materials, (2) the low contact angle hysteresis of surface materials, and
      (3) the space limitation of the shape-gradient transportation area. Furthermore,
      the average velocity and the maximal distance of the self-running were mainly
      determined by the gradient angle (alpha), the droplet volume, and the difference
      of the contact angle hysteresis. Theoretical analysis is in agreement with the
      experimental results.

PMID- 17444661
TI  - Enzymatic catalysis of proton transfer at carbon: activation of triosephosphate
      isomerase by phosphite dianion.
AB  - More than 80% of the rate acceleration for enzymatic catalysis of the aldose
      ketose isomerization of (R)-glyceraldehyde 3-phosphate (GAP) by triosephosphate
      isomerase (TIM) can be attributed to the phosphodianion group of GAP [Amyes, T.
      L., O'Donoghue, A. C., and Richard, J. P. (2001) J. Am. Chem. Soc. 123, 11325
      11326]. We examine here the necessity of the covalent connection between the
      phosphodianion and triose sugar portions of the substrate by "carving up" GAP
      into the minimal neutral two-carbon sugar glycolaldehyde and phosphite dianion
      pieces. This "two-part substrate" preserves both the alpha-hydroxycarbonyl and
      oxydianion portions of GAP. TIM catalyzes proton transfer from glycolaldehyde in
      D2O, resulting in deuterium incorporation that can be monitored by 1H NMR
      spectroscopy, with kcat/Km = 0.26 M-1 s-1. Exogenous phosphite dianion results in
      a very large increase in the observed second-order rate constant (kcat/Km)obsd
      for turnover of glycolaldehyde, and the dependence of (kcat/Km)obsd on [HPO32-]
      exhibits saturation. The data give kcat/Km = 185 M-1 s-1 for turnover of
      glycolaldehyde by TIM that is saturated with phosphite dianion so that the
      separate binding of phosphite dianion to TIM results in a 700-fold acceleration
      of proton transfer from carbon. The binding of phosphite dianion to the free
      enzyme (Kd = 38 mM) is 700-fold weaker than its binding to the fleeting complex
      of TIM with the altered substrate in the transition state (Kd = 53 muM); the
      total intrinsic binding energy of phosphite dianion in the transition state is
      5.8 kcal/mol. We propose a physical model for catalysis by TIM in which the
      intrinsic binding energy of the substrate phosphodianion group is utilized to
      drive closing of the "mobile loop" and a protein conformational change that leads
      to formation of an active site environment that is optimally organized for
      stabilization of the transition state for proton transfer from alpha-carbonyl
      carbon.

PMID- 17444665
TI  - Effect of stabilizer on formation of "onionlike" multilayered polystyrene-block
      poly(methyl methacrylate) particles.
AB  - The effect of the kind of stabilizers on the formation of "onionlike"
      multilayered polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) particles
      was studied. The release of toluene from PS-b-PMMA/toluene droplets dispersed in
      aqueous medium resulted in the formation of onionlike multilayered structures in
      the particles for all stabilizers used. However, the surface composition of the
      particles was strongly affected by the kind of stabilizer. When sodium dodecyl
      sulfate (SDS) and poly(vinyl alcohol) (PVA) were used as stabilizers, the surface
      of the particles was occupied by PMMA phase. On the other hand, in the cases of
      Emulgen 911 (polyoxyethylene nonylphenyl ether) and Tween 80 (polyoxyethylene
      sorbitan monooleate) as stabilizers, the PS phase occupied the surfaces. These
      results for SDS, PVA, and Emulgen 911 are consistent with the surface layer of
      the PS-b-PMMA particles being occupied by the polymer phase, which gives a lower
      interfacial tension than that of another phase. However, in the case of Tween 80,
      interfacial tensions between water and toluene solutions of the polymer showed
      almost the same values making it impossible to predict the surface polymer phase.

PMID- 17444666
TI  - Specific adsorption of histidine-tagged proteins on silica surfaces modified with
      Ni2+/NTA-derivatized poly(ethylene glycol).
AB  - Silica surfaces modified with nitrilotriacetic acid (NTA)-polyethylene glycol
      (PEG) derivatives were used to immobilize hexahistidine-tagged green fluorescent
      protein (His6-GFP), biotin/streptavidin-AlexaFluor555 (His6-biotin/SA-AF), and
      gramicidin A-containing vesicles (His6-gA). Three types of surface-reactive PEG
      derivatives-NTA-PEG3400-Si(OMe)3, NTA-PEG3400-vinylsulfone, and mPEG5000-Si(OMe)3
      (control)-were grafted onto silica and tested for their ability to capture His6
      tag species via His6/Ni2+/NTA chelation. The composition and thicknesses of the
      PEG-modified surfaces were characterized using X-ray photoelectron spectroscopy,
      contact angle, and ellipsometry. Protein capture efficiencies of the NTA-PEG
      grafted surfaces were evaluated by measuring fluorescence intensities of these
      surfaces after exposure to His6-tag species. XPS and ellipsometry data indicate
      that surface adsorption occurs via specific interactions between the His6-tag and
      the Ni2+/NTA-PEG-grafted surface. Protein immobilization was most effective for
      NTA-PEG3400-Si(OMe)3-modified surfaces, with maximal areal densities achieved at
      45 pmol/cm2 for His6-GFP and 95 fmol/cm2 for His6-biotin/SA-AF. Lipid vesicles
      containing His6-gA in a 1:375 gA/lipid ratio could also be immobilized on
      Ni2+/NTA-PEG3400-Si(OMe)3-modified surfaces at 0.5 mM total lipid. Our results
      suggest that NTA-PEG-Si(OMe)3 conjugates may be useful tools for immobilizing
      His6-tag proteins on solid surfaces to produce protein-functionalized surfaces.

PMID- 17444667
TI  - Study of the interactions between protein-imprinted hydrogels and their
      templates.
AB  - The interactions between lysozyme-imprinted hydrogel and their template protein
      were studied using adsorption measurements, competitive adsorption experiments,
      and isothermal titration calorimetry (ITC). The results were compared to the
      interactions between the imprinted polymer and a reference protein, cytochrome c.
      Experimental adsorption isotherms and competitive adsorption studies detected
      better affinity and higher capacity of the imprinted polymer toward the template
      protein. Moreover, analysis of ITC data identified major differences in the
      binding enthalpy of lysozyme when the imprinted and the non-imprinted polymers
      were compared. On the other hand, cytochrome C did not exhibit any major changes
      in the adsorption enthalpy when comparing the imprinted and the non-imprinted
      polymers. This is the first thermodynamic evidence for the creation of new
      binding sites in the process of protein imprinting.

PMID- 17444668
TI  - Searchable high-resolution 2D gel proteome of the human colon crypt.
AB  - We seek alterations in protein patterns at the earliest possible step on the path
      to cancer, namely, in cells of the target tissue from normal persons versus the
      corresponding normally appearing cells from persons who are heterozygous for
      mutation in a tumor suppressor gene that predisposes strongly to carcinoma in
      that tissue. To begin a systematic comparison of the proteomes of cells from
      normal and from neoplastic colons, we have undertaken the isolation of human
      colon crypts that are derived from the normal-appearing mucosa of left
      (descending) colon of patients with sporadic colorectal cancer. Two-dimensional
      (2D) gel electrophoresis is a proteomic approach that excels in the resolution of
      protein isoforms. Here, we document the practicality of this approach with human
      samples using gels of three overlapping pH ranges. For the first time, about 800
      nonredundant proteins and 900 isoforms from purified human colonic crypts were
      identified, permitting an assessment of the contributions of protein isoforms.
      These interactive, searchable, hyperlink-enabled proteome maps and gene ontology
      analyses will facilitate future studies to discover the earliest markers and
      intervention targets during progression to colon cancer.

PMID- 17444669
TI  - Proteomic analysis of rat prefrontal cortex in three phases of morphine-induced
      conditioned place preference.
AB  - Morphological alterations of synapse are found after morphine administration,
      suggesting that regulation of synaptic plasticity may be one of the mechanisms of
      neuroadaptation in addiction. However, the molecular basis underlying the
      abnormal synapse morphological and physiological changes in the morphine-induced
      dependence, withdraw, and relapse is not well understood. As prefrontal cortex
      (PFC) is one of the most important brain regions, which provides executive
      control over drug use and is severely impaired in many addicts, systematic
      analysis of the biochemical and molecular alteration of synaptic fraction of PFC
      in morphine-induced neuroadaptation is necessary. In this study, differential
      protein expression profiling of synaptic fraction of rat PFC based on morphine
      induced conditioned place preference (CPP) model was performed with two
      dimensional gel electrophoresis (2-DE). Our results showed that a total of 80
      proteins were differentially expressed by 2-DE analysis during three phases of
      CPP assay. Of them, 58 were further identified by mass spectrometry. These
      proteins were classified into multiple categories, such as energy metabolism,
      signal transduction, synaptic transmission, cytoskeletal proteins, chaperones,
      and local synaptic protein synthetic machinery according to their biological
      functions. Our study provides a global view of synaptic-related molecular
      networking in PFC under morphine-induced dependence, withdraw, and relapse,
      indicative of a concerted biological process in neuroadaptation under chronic
      morphine exposure.

PMID- 17444670
TI  - Retinal Mueller glial cells trigger the hallmark inflammatory process in
      autoimmune uveitis.
AB  - Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease
      affecting the eye. Although retinal-autoantigen specific T-helper 1 cells have
      been demonstrated to trigger disease progression and relapses, the molecular
      processes leading to retinal degeneration and consequent blindness remain
      unknown. To elucidate such processes, we studied changes in the total retinal
      proteome of ERU-diseased horses compared to healthy controls. Severe changes in
      the retinal proteome were found for several markers for blood-retinal barrier
      breakdown and whose emergence depended upon disease severity. Additionally,
      uveitic changes in the retina were accompanied by upregulation of aldose 1
      epimerase, selenium-binding protein 1, alpha crystallin A chain, phosphatase 2A
      inhibitor (SET), and glial fibrillary acidic protein (GFAP), the latter
      indicating an involvement of retinal Mueller glial cells (RMG) in disease
      process. To confirm this, we screened for additional RMG-specific markers and
      could demonstrate that, in uveitic retinas, RMG concomitantly upregulate vimentin
      and GFAP and downregulate glutamine synthetase. These expression patterns suggest
      for an activated state of RMG, which further downregulate the expression of
      pigment epithelium-derived factor (PEDF) and begin expressing interferon-gamma, a
      pro-inflammatory cytokine typical for T-helper 1 cells. We thus propose that RMG
      may play a fatal role in uveitic disease progression by directly triggering
      inflammatory processes through the expression and secretion of interferon-gamma.

PMID- 17444671
TI  - Large-scale identification of N-terminal peptides in the halophilic archaea
      Halobacterium salinarum and Natronomonas pharaonis.
AB  - Characterization of protein N-terminal peptides supports the quality assessment
      of data derived from genomic sequences (e.g., the correct assignment of start
      codons) and hints to in vivo N-terminal modifications such as N-terminal
      acetylation and removal of the initiator methionine. The current work represents
      the first large-scale identification of N-terminal peptides from prokaryotes, of
      the two halophilic euryarchaeota Halobacterium salinarum and Natronomonas
      pharaonis. Two methods were used that specifically allow the characterization of
      protein N-terminal peptides: combined fractional diagonal chromatography
      (COFRADIC) and strong cation exchange chromatography (SCX), both known to enrich
      for N-terminally blocked peptides. In addition to these specific methods, N
      terminal peptide identifications were extracted from our previous genome-wide
      proteomic data. Combining all data, 606 N-terminal peptides from Hbt. salinarum
      and 328 from Nmn. pharaonis were reliably identified. These results constitute
      the largest available dataset holding identified and characterized protein N
      termini for prokaryotes (archaea and bacteria). They allowed the
      validation/improvement of start codon assignments as automatic gene finders tend
      to misassign start codons for GC-rich genomes. In addition, the dataset allowed
      unravelling N-terminal protein maturation in archaea, showing that 60% of the
      proteins undergo methionine cleavage and that-in contrast to current knowledge
      Nalpha-acetylation is common in the archaeal domain of life with 13-18% of the
      proteins being Nalpha-acetylated. The protein sets described in this paper are
      available by FTP and might be used as reference sets to test the performance of
      new gene finders.

PMID- 17444672
TI  - Electronic excitations in synthetic eumelanin aggregates probed by soft X-ray
      spectroscopies.
AB  - Electronic excitations of condensed phase eumelanin aggregates are investigated
      with soft X-ray spectroscopies. Resonant photoemission data indicate that
      mechanisms of charge delocalization may occur when electrons are excited about 3
      eV above the first unoccupied electronic level. An average, lower limit value of
      1.6 fs was estimated for the lifetime of the excited C 1s-pi* states.

PMID- 17444673
TI  - Energetics and thermodynamic stability of the mixed valence ytterbium germanides.
AB  - The results of an experimental study concerning the thermodynamic stability of
      the Yb germanides, described as intermediate valence compounds, complemented by a
      computational investigation for the Yb3Ge5 compound are reported. These compounds
      belong to the rare earth (RE) tetrelides (tetrel = Si, Ge, i.e., group 14
      elements), a class of intermetallic materials showing unusual and promising
      physical properties (giant magnetocaloric effect, magnetostriction, and
      magnetoresistence). The high-temperature decomposition reactions of the Yb-Ge
      intermediate phases were studied experimentally by means of the KEMS (Knudsen
      effusion mass spectrometry) and KEWL (Knudsen effusion weight loss) techniques.
      From the reaction enthalpies derived by measuring the Yb(g) decomposition
      pressures as a function of temperature, the heats of formation of five out of six
      of the intermediate phases in the Yb-Ge system were calculated. From the
      computational side, the stability of the Yb3Ge5(s) compound has been investigated
      by DFT-LCAO-B3LYP (density functional theory-linear combination of atomic
      orbitals-hybrid b3lyp exchange-correlation functional) first principles
      calculations deriving its equilibrium geometry and the enthalpy of formation at 0
      K in relation to the intermediate valence state of Yb in the lattice.

PMID- 17444674
TI  - Choline saccharinate and choline acesulfamate: ionic liquids with low toxicities.
AB  - Choline saccharinate and choline acesulfamate are two examples of hydrophilic
      ionic liquids, which can be prepared from easily available starting materials
      (choline chloride and a non-nutritive sweetener). The (eco)toxicity of these
      ionic liquids in aqueous solution is very low in comparison to other types of
      ionic liquids. A general method for the synthesis and purification of hydrophilic
      ionic liquids is presented. The method consists of a silver-free metathesis
      reaction, followed by purification of the ionic liquid by ion-exchange
      chromatography. The crystal structures show a marked difference in hydrogen
      bonding between the two ionic liquids, although the saccharinate and the
      acesulfamate anions show structural similarities. The optimized structures, the
      energetics, and the charge distribution of cation-anion pairs in the ionic
      liquids were studied by density functional theory (DFT) and second-order (Moller
      Plesset) perturbation theory calculations. The occupation of the non-Lewis
      orbitals was considered to obtain a qualitative picture of the Lewis structures.
      The calculated interaction energies and the dipole moments for the ion pairs in
      the gas phase were discussed.

PMID- 17444675
TI  - Solvent-driven multiply configurable on/off fluorescent indicator of the pH
      window: a diethylenetriamine bearing two end pyrene fragments.
AB  - Fluorescence behaviors of a simple-structured molecule (L), a diethylenetriamine
      bearing two end pyrene fragments, have been investigated in water. Effects of
      adding a less-polar organic solvent (acetonitrile: MeCN) on the emission
      behaviors have been studied by means of steady-state and time-resolved
      fluorescence measurements. L dissolved in water shows dual-mode fluorescence
      consisting of monomer and excimer emissions. The monomer emission shows an "on
      off" intensity profile against the pH window (pH 2-12), whereas the excimer
      emission shows an "off-on" profile. Upon MeCN addition, the monomer emission
      maintains the "on-off" profile. In contrast, the "off-on" profile of the excimer
      emission is drastically changed: L shows two more types of profiles, "off-on-off
      on" and "off-on-off", along with the MeCN concentration increase, thus behaving
      as a multiply configurable fluorescent indicator of the pH window. The MeCN
      driven excimer emission switching of L is triggered by (i) the decrease in
      stability of the intramolecular ground-state dimer (GSD) formed between the end
      pyrene fragments, which suppresses the direct photoexcitation of GSD (suppression
      of the "static" excimer formation), leading to a decrease in the excimer emission
      intensity at basic pH; and (ii) the decrease in polarity of solution, which
      allows formation of a "dynamic" excimer via a monomer-to-excimer transition,
      resulting in an enhancement of the excimer emission intensity at acidic-neutral
      pH.

PMID- 17444676
TI  - Loading polyelectrolytes onto porous microspheres: impact of molecular and
      electrochemical parameters.
AB  - The impact of macromolecule constitution and electrostatic dimensions on the
      adsorption of cationic model polyelectrolytes (PELs) onto oppositely charged
      porous microspheres (MSs) suspended in aqueous media is demonstrated. The contour
      length (L) of the PEL, the chemical structure of the substituents at the ionic
      group, the ionic strength of the solution (I), and the average pore radius of the
      microspheres (R) are considered as variable. Adsorption isotherms quantitatively
      reveal how PEL parameters, MS geometry, and medium characteristics affect the
      adsorbed amount and surface coverage. Electrostatic exclusion from pores was
      proved as long as the Debye length (lD) exceeded R, even if L was considerably
      smaller than the pore diameter. Two charge parameters (CRcalc and CRexp) and the
      ratio thereof (CR) were derived and served to evaluate the loading process. All
      three parameters are applicable to two limiting cases, first, adsorption only on
      the outer surface of the MS and, second, additional adsorption inside the pores.
      The findings are seen as valuable contributions to basic research in the field of
      PELs. Precise data, which were not available before, are provided for comparison
      with theoretical models and simulations. Overall, conclusions from this model
      system may be useful for technical applications such as surface modification,
      chromatographic processes, or materials development.

PMID- 17444677
TI  - Conduction band mediated electron transfer across nanocrystalline TiO2 surfaces.
AB  - Mesoporous thin films comprised of interconnected nanocrystalline (anatase, 20
      nm) TiO2 particles were functionalized with [Ru(bpy)2(deebq)](PF6)2, where bpy is
      2,2'-bipyridine and deebq is 4,4'-diethylester-2,2'-biquinoline, or iron(III)
      protoporphyrin IX chloride (hemin). These compounds bind to TiO2 with saturation
      surface coverages of 8 (+/-2)x10(-8) mol/cm2. Electrochemical measurements show
      that the compounds first reduction occurs prior to or commensurate with the
      reduction of the TiO2 electrode. Apparent diffusion constants, Dapp, abstracted
      from chronoabsorption data measured in acetonitrile were found to be dependent on
      the applied potential and the electrolyte used. The Dapp values for reduction of
      Ru(dcbq)(bpy)2/TiO2, where dcbq is 4,4'-(COO-)2-2,2'-biquinoline, increased with
      decreasing surface coverage. At near saturation surface coverage, the apparent
      diffusion constant was 9.0 x 10(-12) m2/s after a potential step from -0.61 to 
      1.31 vs Fc+/0. The Dapp varied by over a factor of six with applied potential for
      the oxidation of [Ru(dcbq-)(bpy)2]-/TiO2 to Ru(dcbq)(bpy)2/TiO2. Complete
      reduction of hemin/TiO2 to heme/TiO2 was observed under conditions where the heme
      surface coverage was about 1/100 of that expected for monolayer surface coverage.
      The hemin reduction rates were strongly dependent on the final applied potential.
      The rates for heme to hemin oxidation were less than or equal to the hemin to
      heme rates in the presence and absence of pyridine. This behavior was opposite to
      that observed with Ru(dcbq)(bpy)2/TiO2 where reduction was slower than oxidation.
      A Gerischer-type model was proposed to rationalize the rectifying properties of
      the interface.

PMID- 17444678
TI  - Multifrequency EPR studies on the Mn(II) centers of oxalate decarboxylase.
AB  - Oxalate decarboxylase from Bacillus subtilis is composed of two cupin domains,
      each of which contains a Mn(II) ion coordinated by four identical conserved
      residues. The similarity between the two Mn(II) sites has precluded previous
      attempts to distinguish them spectroscopically and complicated efforts to
      understand the catalytic mechanism. A multifrequency cw-EPR approach has now
      enabled us to show that the two Mn ions can be distinguished on the basis of
      their differing fine structure parameters and to observe that acetate and formate
      bind to Mn(II) in only one of the two sites. The EPR evidence is consistent with
      the hypothesis that this Mn-binding site is located in the N-terminal domain, in
      agreement with predictions based on a recent X-ray structure of the enzyme.

PMID- 17444679
TI  - Protein immobilization strategies for protein biochips.
AB  - In the past few years, protein biochips have emerged as promising proteomic and
      diagnostic tools for obtaining information about protein functions and
      interactions. Important technological innovations have been made. However,
      considerable development is still required, especially regarding protein
      immobilization, in order to fully realize the potential of protein biochips. In
      fact, protein immobilization is the key to the success of microarray technology.
      Proteins need to be immobilized onto surfaces with high density in order to allow
      the usage of small amount of sample solution. Nonspecific protein adsorption
      needs to be avoided or at least minimized in order to improve detection
      performances. Moreover, full retention of protein conformation and activity is a
      challenging task to be accomplished. Although a large number of review papers on
      protein biochips have been published in recent years, few have focused on protein
      immobilization technology. In this review, current protein immobilization
      strategies, including physical, covalent, and bioaffinity immobilization for the
      fabrication of protein biochips, are described. Particular consideration has been
      given to oriented immobilization, also referred to as site-specific
      immobilization, which is believed will improve homogeneous surface covering and
      accessibility of the active site.

PMID- 17444680
TI  - Direct amidation of poly(gamma-glutamic acid) with benzylamine in dimethyl
      sulfoxide.
AB  - Partially benzylamidated, amphipathic poly(gamma-glutamic acid) (BzPGA) was
      synthesized from poly(gamma-glutamic acid) (PGA) and benzylamine by direct
      amidation in dimethyl sulfoxide (DMSO). Benzylamine and PGA were heated in DMSO
      for 1 to 26 h at temperatures between 110 and 130 degrees C, producing
      derivatives of various degrees of benzylamidation as a function of the reaction
      time and temperature. Neither any carboxyl-activating agent nor catalyst is
      needed for the reaction to proceed. After purification by dialysis, the product
      was identified by 1H and 13C 1D and 2D NMR in DMSO-d(6). BzPGA prepared by the
      new direct amidation method was identical to that obtained with a conventional
      carbodiimide-mediated reaction in water. The one-pot amidation procedure
      described in the present article can probably be applied to the synthesis of
      amides from other amines and carboxylic acids.

PMID- 17444681
TI  - Spermidine and spermine catalyze the formation of nanostructured titanium oxide.
AB  - Naturally occurring polyamines putrescine, cadaverine, spermidine, and spermine
      are analogues of the species-specific long-chain polyamines found in diatoms.
      Scanning electron microscopy and energy-dispersive spectroscopy show that the
      reactions of a soluble Ti(IV) precursor with spermidine and spermine, but not
      putrescine or cadaverine, produce nanostructured irregular polyhedra of titanium
      oxide. At 25 degrees C, the average size of the particles formed with spermidine
      is 400 +/- 150 nm, and with spermine, 140 +/- 50 nm. Although the particles are X
      ray amorphous at room temperature, annealing studies reveal that the particles
      adopt crystallinity at higher temperatures characteristic of anatase (TiO2). The
      major portion of the biopolyamines is not coprecipitated with the solid but is
      left in solution. Kinetic measurements reveal an initial fast step followed by
      two slower phases of reaction. At 25 degrees C, k(1obs) and k(2obs) for the
      reaction with spermidine are 5 x 10(-3) s(-1) and 3.6 x 10(-4) s(-1),
      respectively, and for spermine, 4.8 x 10(-3) s(-1) and 4.2 x 10(-4) s(-1),
      respectively. Taken together, the data suggest spermidine and spermine are
      biocatalysts for the precipitation of nanostructured titanium oxide.

PMID- 17444682
TI  - Effect of water content on the structural reorganization and elastic properties
      of biopolymer films: a comparative study.
AB  - In this work, the effect of water uptake on the structural reorganization and
      elastic properties of three types of biopolymer films was studied. The water
      biopolymer interaction for hydroxypropyl cellulose (HPC), gelatin, and cassava
      starch films prepared from aqueous solutions was studied and compared using
      Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry
      (DSC), X-ray diffraction, dynamic vapor sorption (DVS), and dynamic mechanical
      thermal analysis with humidity generator and controller (DMTA) techniques. The
      FTIR spectral variations due to the water sorption were generalized into two
      dimensional (2D) correlation graphs for each biopolymer, and the effect of water
      on the molecular conformation was compared. The water sorption isotherms were
      fitted with Guggenheim-Anderson-De Boer (GAB) and D'Arcy and Watt models. The
      water content in the mono- and multilayers predicted by both models for each
      biopolymer was discussed and compared. The correlation of the fitted data
      obtained from the sorption isotherms to the DMTA data allowed us to conclude that
      the elastic properties of the HPC films depended on the total water content in
      contrast to the elastic properties of the gelatin and cassava starch films, which
      decrease only with the appearance of multilayer water.

PMID- 17444683
TI  - Protein immobilization on aminated poly(glycidyl methacrylate) nanofibers as
      polymeric carriers.
AB  - Recently, protein carriers based on nanomaterials have been highlighted in
      diverse biological applications such as protein extraction, separation, and
      delivery due to their facile gravimetric sedimentation in the aqueous phase and
      abundant surface functionalities, which were used as anchoring sites for
      proteins. From this viewpoint, poly(glycidyl methacrylate) nanofibers (PGMA NFs)
      can be an excellent candidate for protein support because PGMA NFs possess the
      activated epoxide functional groups on the surface. In addition, cured PGMA NFs
      (PGMA-NH2 NFs) reveal different surface functionalities such as primary amine
      groups. They can be linked with carboxylated proteins. Ferritin and streptavidin
      were selected as models of the pristine and biolinker-mediated proteins in this
      experiment and immobilized onto PGMA NFs and aminated PGMA-NH2 NFs. The
      successful conjugations of ferritin and streptavidin were confirmed with
      transmission electron microscopy and fluorescein-isothiocyanate-tagged molecules.
      Protein immobilization using the pristine and the cured PGMA NFs could be
      considered as an outstanding protocol for facile protein delivery.

PMID- 17444684
TI  - Highly enantioselective Pd-catalyzed asymmetric hydrogenation of activated
      imines.
AB  - Pd/bisphosphines complexes are highly effective catalysts for asymmetric
      hydrogenation of activated imines in trifluoroethanol. The asymmetric
      hydrogenation of N-diphenylphosphinyl ketimines 3 with Pd(CF3CO2)/(S)-SegPhos
      indicated 87-99% ee, and N-tosylimines 5 could gave 88-97% ee with Pd(CF3CO2)/(S)
      SynPhos as a catalyst. Cyclic N-sulfonylimines 7 and 11 were hydrogenated to
      afford the useful chiral sultam derivatives in 79-93% ee, which are important
      organic synthetic intermediates and structural units of agricultural and
      pharmaceutical agents.

PMID- 17444685
TI  - Trichloromethyltrimethylsilane, sodium formate, and dimethylformamide: a mild,
      efficient, and general method for the preparation of trimethylsilyl-protected
      2,2,2-trichloromethylcarbinols from aldehydes and ketones.
AB  - New conditions for the preparation of trimethylsilyl-protected 2,2,2
      trichloromethylcarbinols 2 from aldehydes and ketones are reported. Compounds 2,
      which are important intermediates in organic synthesis, were obtained in
      excellent yields by use of a combination of trichloromethyltrimethylsilane
      (TMSCCl3), and a catalytic amount of sodium formate (HCOONa) in dimethylformamide
      (DMF). Substrates bearing highly sensitive protecting groups have been
      successfully subjected to our conditions. We also describe a one-pot procedure
      that gives direct access to 2,2,2-trichloromethylcarbinols 3. This methodology
      avoids the use of strong bases usually required for the synthesis of 3 (Wyvratt
      et al. J. Org. Chem. 1987, 52, 944; Aggarwal and Mereu, J. Org. Chem. 2000, 65,
      7211).

PMID- 17444686
TI  - A tricatecholic receptor for carbohydrate recognition: synthesis and binding
      studies.
AB  - A new tripodal receptor bearing three catechol subunits on a benzene platform has
      been synthesized in four steps from 1,3,5-triethylbenzene and pyrogallol. The
      binding ability of the tricatecholic receptor was investigated toward several
      monosaccharides in CDCl3, where multiple equilibria were detected, and compared
      to that of a previously reported trisureidic receptor of analogous structure.
      Association constants were measured by 1H NMR titrations, and the corresponding
      affinities were assessed through the BC50 parameter, a binding descriptor
      univocally defining the affinity of a host for a guest in multi-equilibrium
      systems. Results show that the tripodal catecholic receptor binds the octyl
      glycosides with affinities ranging from 0.87 to 5.2 mM and with a 6-fold
      selectivity factor for the alpha-mannoside over the beta-glucoside. Although the
      affinity for glycosides was not appreciably improved with respect to the ureidic
      receptor, a significant change in selectivity was obtained by the H-bonding group
      replacement.

PMID- 17444687
TI  - Isothiocyanates from tosyl chloride mediated decomposition of in situ generated
      dithiocarbamic acid salts.
AB  - A facile and general protocol for the preparation of isothiocyanates from alkyl
      and aryl amines is reported. This method relies on a tosyl chloride mediated
      decomposition of a dithiocarbamate salt that is generated in situ by treatment of
      an amine with carbon disulfide and triethylamine. Utilizing this protocol, we
      have prepared 19-alkyl- and arylisothiocyanates in moderate to excellent yield.

PMID- 17444689
TI  - Recent advances in the Hauser annulation.

PMID- 17444688
TI  - Total synthesis of marine sponge bis(indole) alkaloids of the topsentin class.
AB  - The synthesis of four natural bis(indole) alkaloids of topsentin class 1 and 2 is
      described. Their bis(indole) alpha-carbonylimidazoline and subsequently
      bis(indole) alpha-carbonylimidazole moieties have been built via the condensation
      between indolic alpha-ketothioimidate salts 4 and 1-(indol-3'-yl)-1,2
      diaminoethane 3. This compound results from the beta-amino indolic hydroxylamine
      5 by a two-step sequence. This is the first total synthesis of compounds 1d, 2a,
      and 2b.

PMID- 17444690
TI  - Aspect ratio dependence of the elastic properties of ZnO nanobelts.
AB  - The Young's modulus of ZnO nanobelts was measured with an atomic force microscope
      by means of the modulated nanoindentation method. The elastic modulus was found
      to depend strongly on the width-to-thickness ratio of the nanobelt, decreasing
      from about 100 to 10 GPa, as the width-to-thickness ratio increases from 1.2 to
      10.3. This surprising behavior is explained by a growth-direction-dependent
      aspect ratio and the presence of stacking faults in nanobelts growing along
      particular directions.

PMID- 17444691
TI  - Topologically controlled growth of magnetic-metal-functionalized semiconductor
      oxide nanorods.
AB  - Colloidal semiconductor-magnetic hybrid nanocrystals with topologically
      controlled composition are fabricated by heterogeneous nucleation of spherical
      epsilon-Co domains onto anatase TiO2 nanorods. The latter can be selectively
      decorated at either their tips or at multiple locations along their longitudinal
      sidewalls, forming lattice-matched heterointerfaces regardless of the metal
      deposition sites. The possibility of switching between either heterostructure
      growth modes arises from the facet-dependent chemical reactivity of the oxide
      seeds, which is governed mainly by selective adhesion of the surfactants rather
      than by small differences in misfit-induced interfacial strain at the relevant
      junction points.

PMID- 17444692
TI  - Electronic spectra of jet-cooled calix[4]arene and its van der Waals clusters:
      encapsulation of a neutral atom in a molecular bowl.
AB  - The encapsulation of neutral guest has been studied for calix[4]arene (C4A) by
      forming van der Waals clusters with Ar and Ne in supersonic jets. The electronic
      transitions of these clusters suggest that the first Ar (Ne) is encapsulated
      inside the C4A cavity, while the next atoms are bound outside.

PMID- 17444693
TI  - Transient diffusion and cluster formation of water molecules on Rh(111) at 20 K.
AB  - The authors investigated the initial stage of water adsorption on Rh(111) at 20
      K, using infrared reflection absorption spectroscopy. In this low coverage
      region, isolated water molecules and small water clusters are observed. Since
      thermal diffusion is suppressed at 20 K, the formation of water clusters at low
      coverage is controlled by both coverage and transient diffusion on the surface.
      Within a simple random walk model of the transient diffusion and clustering
      process, the authors estimate the mean lateral displacement from the first impact
      point to the final adsorption site to be 7.6 A; an incoming water molecule on
      Rh(111) is trapped with eight postcollision hops on the average.

PMID- 17444694
TI  - Ab initio photoionization dynamics of beta-alanine.
AB  - Photoionization dynamics of beta-alanine is studied by the trajectory simulations
      using the ab initio potential energy surface. Vertical photoionization in the
      spirit of the Franck-Condon principle is assumed both for the adiabatic and
      thermostatic simulations. Both intramolecular proton transfer and fragmentation
      while only the proton transfer are found in the thermostatic and adiabatic
      simulations, respectively, for the conformer having the intramolecular hydrogen
      bond N...H-O. The theoretical predictions are in line with the experimental
      observations available in the literatures. It is reported for the first time that
      the thermostatic temperatures strongly affect the fragmentation processes induced
      by photoionization.

PMID- 17444695
TI  - Improving the accuracy of density-functional theory calculation: the genetic
      algorithm and neural network approach.
AB  - The combination of genetic algorithm and neural network approach (GANN) has been
      developed to improve the calculation accuracy of density functional theory. As a
      demonstration, this combined quantum mechanical calculation and GANN correction
      approach has been applied to evaluate the optical absorption energies of 150
      organic molecules. The neural network approach reduces the root-mean-square (rms)
      deviation of the calculated absorption energies of 150 organic molecules from
      0.47 to 0.22 eV for the TDDFTB3LYP6-31G(d) calculation, and the newly developed
      GANN correction approach reduces the rms deviation to 0.16 eV.

PMID- 17444696
TI  - Sampling diffusive transition paths.
AB  - The authors address the problem of sampling double-ended diffusive paths. The
      ensemble of paths is expressed using a symmetric version of the Onsager-Machlup
      formula, which only requires evaluation of the force field and which, upon direct
      time discretization, gives rise to a symmetric integrator that is accurate to
      second order. Efficiently sampling this ensemble requires avoiding the well-known
      stiffness problem associated with the sampling of infinitesimal Brownian
      increments of the path, as well as a different type of stiffness associated with
      the sampling of the coarse features of long paths. The fine-feature sampling
      stiffness is eliminated with the use of the fast sampling algorithm, and the
      coarse-feature sampling stiffness is avoided by introducing the sliding and
      sampling (S&S) algorithm. A key feature of the S&S algorithm is that it enables
      massively parallel computers to sample diffusive trajectories that are long in
      time. The authors use the algorithm to sample the transition path ensemble for
      the structural interconversion of the 38-atom Lennard-Jones cluster at low
      temperature.

PMID- 17444697
TI  - Time-reversible ab initio molecular dynamics.
AB  - Time-reversible ab initio molecular dynamics based on a lossless multichannel
      decomposition for the integration of the electronic degrees of freedom [Phys.
      Rev. Lett. 97, 123001 (2006)] is explored. The authors present a lossless time
      reversible density matrix molecular dynamics scheme. This approach often allows
      for stable Hartree-Fock simulations using only one single self-consistent field
      cycle per time step. They also present a generalization, introducing an
      additional "forcing" term, that in a special case includes a hybrid Lagrangian,
      i.e., Car-Parrinello-type, method, which can systematically be constrained to the
      Born-Oppenheimer potential energy surface by using an increasing number of self
      consistency cycles in the nuclear force calculations. Furthermore, in analog to
      the reversible and symplectic leapfrog or velocity Verlet schemes, where not only
      the position but also the velocity is propagated, the authors propose a Verlet
      type density velocity formalism for time-reversible Born-Oppenheimer molecular
      dynamics.

PMID- 17444698
TI  - Source and sink potentials for the description of open systems with a stationary
      current passing through.
AB  - The authors present a model Hamiltonian for the description of open systems that
      exchange probability current density with their surroundings. The complex
      potentials appearing in this Hamiltonian act as source and sink, respectively, of
      probability current density. The primary applications of the theory of source and
      sink potentials are molecular electronic devices (MEDs), in the description of
      which the semi-infinite contacts are replaced by complex potentials. This is done
      in a rigorous manner, i.e., the exact wave function is recovered in the interior
      of the MED. To illustrate the approach, certain prototypical molecular conductors
      are considered in the Huckel approximation. The authors show that, for the
      examples considered, there exist almost isolated molecular states in the
      continuum of contact states that manifest themselves as Fano resonances in the
      transmission probability. The findings are confirmed by density functional theory
      calculations that also yield the predicted molecular states that are nearly
      decoupled from the contacts.

PMID- 17444699
TI  - Assessment of the efficiency of long-range corrected functionals for some
      properties of large compounds.
AB  - Using the long-range correction (LC) density functional theory (DFT) scheme
      introduced by Iikura et al. [J. Chem. Phys. 115, 3540 (2001)] and the Coulomb
      attenuating model (CAM-B3LYP) of Yanai et al. [Chem. Phys. Lett. 393, 51 (2004)],
      we have calculated a series of properties that are known to be poorly reproduced
      by standard functionals: Bond length alternation of pi-conjugated polymers,
      polarizabilities of delocalized chains, and electronic spectra of extended dyes.
      For each of these properties, we present cases in which traditional hybrid
      functionals do provide accurate results and cases in which they fail to reproduce
      the correct trends. The quality of the results is assessed with regard to
      experimental values and/or data arising from electron-correlated wave function
      approaches. It turns out that (i) both LC-DFT and CAM-B3LYP provide an accurate
      bond length alternation for polyacetylene and polymethineimine, although for the
      latter they decrease slightly too rapidly with chain length. (ii) The LC
      generalized gradient approximation and MP2 polarizabilities of long
      polyphosphazene and polymethineimine oligomers agree almost perfectly. In the
      same way, CAM-B3LYP corrects the major part of the B3LYP faults. (iii) LC and CAM
      techniques do not help in correcting the nonrealistic evolution with chain length
      of the absorption wavelengths of cyanine derivatives. In addition, though both
      schemes significantly overestimate the ground to excited state transition energy
      of substituted anthraquinone dyes, they provide a more consistent picture once a
      statistical treatment is performed than do traditional hybrid functionals.

PMID- 17444700
TI  - Gaussian and finite-element Coulomb method for the fast evaluation of Coulomb
      integrals.
AB  - The authors propose a new linear-scaling method for the fast evaluation of
      Coulomb integrals with Gaussian basis functions called the Gaussian and finite
      element Coulomb (GFC) method. In this method, the Coulomb potential is expanded
      in a basis of mixed Gaussian and finite-element auxiliary functions that express
      the core and smooth Coulomb potentials, respectively. Coulomb integrals can be
      evaluated by three-center one-electron overlap integrals among two Gaussian basis
      functions and one mixed auxiliary function. Thus, the computational cost and
      scaling for large molecules are drastically reduced. Several applications to
      molecular systems show that the GFC method is more efficient than the analytical
      integration approach that requires four-center two-electron repulsion integrals.
      The GFC method realizes a near linear scaling for both one-dimensional alanine
      alpha-helix chains and three-dimensional diamond pieces.

PMID- 17444701
TI  - Simple implementation of complex functionals: scaled self-consistency.
AB  - We explore and compare three approximate schemes allowing simple implementation
      of complex density functionals by making use of self-consistent implementation of
      simpler functionals: (i) post-local-density approximation (LDA) evaluation of
      complex functionals at the LDA densities (or those of other simple functionals)
      (ii) application of a global scaling factor to the potential of the simple
      functional, and (iii) application of a local scaling factor to that potential.
      Option (i) is a common choice in density-functional calculations. Option (ii) was
      recently proposed by Cafiero and Gonzalez [Phys. Rev. A 71, 042505 (2005)]. We
      here put their proposal on a more rigorous basis, by deriving it, and explaining
      why it works, directly from the theorems of density-functional theory. Option
      (iii) is proposed here for the first time. We provide detailed comparisons of the
      three approaches among each other and with fully self-consistent implementations
      for Hartree, local-density, generalized-gradient, self-interaction corrected, and
      meta-generalized-gradient approximations, for atoms, ions, quantum wells, and
      model Hamiltonians. Scaled approaches turn out to be, on average, better than
      post approaches, and unlike these also provide corrections to eigenvalues and
      orbitals. Scaled self-consistency thus opens the possibility of efficient and
      reliable implementation of density functionals of hitherto unprecedented
      complexity.

PMID- 17444702
TI  - Alternatives to the electron density for describing Coulomb systems.
AB  - Stimulated by the difficulty of deriving effective kinetic energy functionals of
      the electron density, the authors consider using the local kinetic energy as the
      fundamental descriptor for molecular systems. In this ansatz, the electron
      density must be expressed as a functional of the local kinetic energy. There are
      similar results for other quantities, including the local temperature and the
      Kohn-Sham potential. One potential advantage of these approaches--and especially
      the approach based on the local temperature--is the chemical relevance of the
      fundamental descriptor.

PMID- 17444703
TI  - Synergistic approach to improve "alchemical" free energy calculation in rugged
      energy surface.
AB  - The authors present an integrated approach to "alchemical" free energy
      simulation, which permits efficient calculation of the free energy difference on
      rugged energy surface. The method is designed to obtain efficient canonical
      sampling for rapid free energy convergence. The proposal is motivated by the
      insight that both the exchange efficiency in the presently designed dual-topology
      alchemical Hamiltonian replica exchange method (HREM), and the confidence of the
      free energy determination using the overlap histogramming method, depend on the
      same criterion, viz., the overlaps of the energy difference histograms between
      all pairs of neighboring states. Hence, integrating these two techniques can
      produce a joint solution to the problems of the free energy convergence and
      conformational sampling in the free energy simulations, in which lambda parameter
      plays two roles to simultaneously facilitate the conformational sampling and
      improve the phase space overlap for the free energy determination. Specifically,
      in contrast with other alchemical HREM based free energy simulation methods, the
      dual-topology approach can ensure robust conformational sampling. Due to these
      features (a synergistic solution to the free energy convergence and canonical
      sampling, and the improvement of the sampling efficiency with the dual-topology
      treatment), the present approach, as demonstrated in the model studies of the
      authors, is highly efficient in obtaining accurate free energy differences,
      especially for the systems with rough energy landscapes.

PMID- 17444704
TI  - Direct optimization of nodal hypersurfaces in approximate wave functions.
AB  - The fixed-node variant of the diffusion quantum Monte Carlo method (FN-DMC) is
      capable of obtaining the exact eigenvalues (albeit numerically with statistical
      error) of a many-electron Hamilton operator, provided that the nodal hypersurface
      of the exact wave function is given. The use of nodes of a trial wave function
      leads to the node location error. The authors have developed local criteria to
      assess the accuracy of the nodes based on the distances of the nodal
      hypersurfaces of PsiT, TPsiT, and HPsiT which coincide for the exact wave
      function. These criteria are used to develop direct optimization methods for the
      nodal hypersurface. The optimization of the nodes is demonstrated for simple wave
      functions of the Be atom and the C2 molecule and verified with FN-DMC
      calculations.

PMID- 17444705
TI  - Critical analysis and extension of the Hirshfeld atoms in molecules.
AB  - The computational approach to the Hirshfeld [Theor. Chim. Acta 44, 129 (1977)]
      atom in a molecule is critically investigated, and several difficulties are
      highlighted. It is shown that these difficulties are mitigated by an alternative,
      iterative version, of the Hirshfeld partitioning procedure. The iterative scheme
      ensures that the Hirshfeld definition represents a mathematically proper
      information entropy, allows the Hirshfeld approach to be used for charged
      molecules, eliminates arbitrariness in the choice of the promolecule, and
      increases the magnitudes of the charges. The resulting "Hirshfeld-I charges"
      correlate well with electrostatic potential derived atomic charges.

PMID- 17444706
TI  - Unusual halogen-bonded complex FBrdelta+...delta+BrF and hydrogen-bonded complex
      FBrdelta+...delta+HF formed by interactions between two positively charged atoms
      of different polar molecules.
AB  - Using ab initio calculations, the authors' predicted for the first time that the
      halogen-bonded complex FBrdelta+...delta+BrF and hydrogen-bonded complex
      FBrdelta+...delta+HF formed by the interactions between two positively charged
      atoms of different polar molecules can be stable in gas phase. It shows that
      halogen bond or hydrogen bond not only exists between oppositely charged atoms
      but also between like-charged atoms. That the attraction arising from the special
      halogen bond or hydrogen bond can exceed the electrostatic repulsion between two
      contact positively charged atoms stabilizes the complex. Of course, from the
      point of view of physics they can consider the interactions in
      FBrdelta+...delta+BrF and FBrdelta+...delta+HF as mainly the sum of the long
      range molecular interactions, namely, electrostatic, induction, and dispersion
      with some short-range repulsion. They found that the intermolecular electron
      correlation contribution representing dispersion interaction plays a crucial role
      in the stabilities of seemingly repulsive complexes FBrdelta+...delta+BrF and
      FBrdelta+...delta+HF.

PMID- 17444707
TI  - Photodissociation dynamics of the 2-propyl radical, C3H7.
AB  - The photodissociation of 2-propyl leading to propene+H was investigated with
      nanosecond time resolution. A supersonic beam of isolated 2-propyl radicals was
      produced by pyrolysis of 2-bromopopane. The kinetic energy release of the H-atom
      photofragment was monitored as a function of excitation wavelength by
      photofragment Doppler spectroscopy via the Lyman-alpha transition. The loss of
      hydrogen atoms after excitation proceeds in alpha position to the radical center
      with a rate constant of 5.8x10(7) s-1 at 254 nm. Approximately 20% of the excess
      energy is deposited as translation in the H-atom photofragment. In contrast 1
      propyl does not lose H atoms to a significant extent. The experimental results
      are compared to simple Rice-Ramsperger-Kassel-Marcus calculations. The possible
      reaction pathways are examined in hybrid density functional theory calculations.

PMID- 17444708
TI  - Study of the B"B 1Sigmau+ state of H2: transition probabilities from the ground
      state, dissociative widths, and Fano parameters.
AB  - The transition probabilities, the dissociation widths, and the associated Fano
      parameters for rovibronic lines with J"=0,...,3 of the absorption bands of the
      B"B 1Sigmau+ state out of the X 1Sigmag+ v"=0 ground state were measured over the
      complete vibrational progression, showing clearly that only the inner-well state
      with B" 4psigma character can absorb vuv light and predissociate efficiently. The
      absolute values of these transition probablities, predissociation widths, and
      Fano parameters were found to agree well with ab initio calculations if one takes
      into account that the calculations neglect nonadiabatic couplings.

PMID- 17444709
TI  - Symmetry segregation of the vibronic levels within the S1<--S0 system of
      thiophosgene, Cl2CS, by optical-optical double resonance spectroscopy.
AB  - The first singlet-singlet electronic system, S1<--S0, in thiophosgene has been
      recorded as a laser induced fluorescence (LIF) excitation and an optical-optical
      double resonance (OODR) spectrum under jet-cooled conditions. In the OODR
      process, the sum of the frequencies of the pump and probe lasers must be fixed to
      the energy difference between a pair of vibronic levels in the S2(v') and S0(v")
      states. Detection is through the fluorescence from the S2 state. The blocking of
      a spectrum into its four possible symmetry components is obtained by adjusting
      the total pump+probe energy such that it matches the energy difference between
      symmetry selected levels in the S2 and S0 electronic states. In this method the
      pump laser is used to excite a group of "hot" sequence bands that involve
      combinations of the nu4 and nu6 antisymmetric vibrations. The additional data
      that were collected by this method were used to update and refine the analyses of
      the spectrum. Magnetic dipole transitions are reported for the first time.

PMID- 17444710
TI  - Jahn-Teller effect in tetrahedral symmetry: large-amplitude tunneling motion and
      rovibronic structure of CH4+ and CD4+.
AB  - The energy level structures of the ground vibronic states of 12CH4+, 13CH4+, and
      12CD4+ have been measured by pulsed-field-ionization zero-kinetic-energy
      photoelectron spectroscopy. The nuclear spin symmetries of the tunneling
      rotational levels have been determined in double-resonance experiments via
      selected rotational levels of the v3=1 and v3=2 vibrational levels of the X 1A1
      ground state of CH4. The energy level structures of 12CH4+, 13CH4+, and 12CD4+
      have been analyzed with an effective tunneling-rotational Hamiltonian. The
      analysis together with a group theoretical treatment of the Tx(e+t2) Jahn-Teller
      effect in the Td(M) group prove that the equilibrium geometry of 12CH4+, 13CH4+,
      and 12CD4+ has C2v symmetry and characterize the pseudorotational dynamics in
      these fluxional cations. The tunneling behavior is discussed in terms of the
      relevant properties of the potential energy surface, some of which have been
      recalculated at the CCSD(T)/cc-pVTZ level of ab initio theory.

PMID- 17444711
TI  - Most stable structure of fullerene[20] and its novel activity toward addition of
      alkene: a theoretical study.
AB  - Structures and stabilities of fullerene C20 and C20- have been investigated by
      the density functional theory and CCSD(T) calculations. In consideration of the
      Jahn-Teller distortion of Ih-symmetric C20, possible subgroup symmetries have
      been used in the full geometry optimization. On the basis of relative energetics,
      vibrational analyses, and electron affinities, fullerenes C20 and C20- have most
      stable D2h and Ci structures, respectively. The controversy on the relative
      stability of fullerene[20] arises from the use of different subgroups in
      calculation and the basis set dependence in vibrational analysis. Predicted
      nucleus-independent chemical shift values show that the most stable fullerene C20
      and its derivatives C20(C2H2)n and C20(C2H4)n (n=1-3) exhibit remarkable
      aromaticity, while C20(C2H2)4 and C20(C2H4)4 have no spherical aromaticity. The
      C20 (D2h) cage has remarkable activity toward the addition of olefin, and such
      feasibility of the addition reaction is ascribed to strong bonding interactions
      among frontier molecular orbitals from C20 and olefin. Calculations indicate that
      both C20(C2H2)n and C20(C2H4)n have similar features in electronic spectra.

PMID- 17444712
TI  - Ab initio calculation of the electronic structures of the 3Phi ground and 5Phi
      excited states of CoH.
AB  - The electronic structures and the spectroscopic constants of the electronic
      ground 3Phi and low-lying 5Phi electronic excited states of the CoH molecule were
      studied by multireference single and double excitation configuration interaction
      (MR-SDCI)+Davidson's correction (Q) calculations and size-consistent
      multireference coupled pair approximation (MRCPA) calculations. Calculations were
      performed under Cinfinityv symmetry using Slater-type basis functions. The
      electronic ground state was confirmed to be the 3Phi state. It was found that at
      least four reference configurations were needed to describe the ground 3Phi state
      correctly at the MR-SDCI+Q level, while the 5Phi state can be described well by
      one reference configuration, namely, the Hartree-Fock configuration. Larger
      dynamical electron correlation for the low-spin 3Phi state than that for the high
      spin 5Phi state is discussed. Spectroscopic constants, i.e., equilibrium bond
      lengths (re), harmonic frequency (omegae), and excitation energy, obtained by the
      MR-SDCI+Q method showed good correspondence with experimental values. MRCPA
      calculations gave a slightly shorter value for re than experimental values, but
      improved omegae and the excitation energy bringing them very close to
      experimental values.

PMID- 17444713
TI  - Coupled cluster study of the energetic properties of S2x (x=0,+1,1).
AB  - Ab initio electronic structure calculations are reported for S2, and its ions S2+
      and S2-. Geometric parameters are calculated using the singles and doubles
      coupled cluster method, including a perturbational correction for connected
      triple excitation, together with systematic sequences of correlation consistent
      basis sets extrapolated to the complete basis set (CBS) limit. Energetic and
      structural properties of S2 and the S2 cation and anion are reported. The heat of
      formation of S2 (3Sigmag-) at 0 K in the gas phase is predicted to be 29.8
      kcal/mol from the average of CBS two extrapolation procedures, less than the
      experimental heat of formation of S2 of 30.66+/-0.07 kcal/mol. The 0 K adiabatic
      ionization potential and electron affinity are predicted to be 9.37 and 1.68 eV,
      respectively.

PMID- 17444714
TI  - Spin-forbidden c 3Sigma1+<--X 1Sigma+ band system of YF.
AB  - Optical spectra of jet-cooled diatomic YF have been recorded using resonant two
      photon ionization spectroscopy. A vibrational progression corresponding to the c
      3Sigma1+<--X 1Sigma+ system has been identified. The vibrational frequency
      omegae' and anharmonicity omegae'xe' of the c 3Sigma+ state are 546.70 and 2.45
      cm-1, respectively. The 0-0, 1-0, and 2-0 bands of the c 3Sigma1+<--X 1Sigma+
      system were rotationally resolved and analyzed, allowing the v'=0, 1, and 2
      levels of the c 3Sigma1+ substate to be characterized. From these studies,
      Be'=0.269 81(3) cm-1, alphae'=0.001 72(3) cm-1, and re'=1.9979(1) A were obtained
      (1sigma error limits). For these levels the spin-spin coupling constant lambdav
      is identical within experimental error, as lambda=-22.5 cm-1. The spin-forbidden
      c 3Sigma1+<--X 1Sigma+ transition is made allowed by spin-orbit interaction
      between the c 3Sigma1+ and the B 1Pi states. Excited state lifetimes of the c
      3Sigma1+ and the B 1Pi states have been measured as 7.11(41) and 0.133(15)
      micros, respectively. A spin-orbit analysis shows that the c 3Sigma1+ state is
      contaminated with 2% B 1Pi character, which is approximately sufficient to
      explain the 7 micros lifetime of the c 3Sigma1+ state.

PMID- 17444715
TI  - PtF6(2-) dianion and its detachment spectrum: a fully relativistic study.
AB  - In this work we calculate the photoelectron spectrum of the PtF(6)2- dianion by
      application of the third-order Dirac-Hartree-Fock one-particle propagator
      technique. Relativistic effects and electron correlation are hereby treated on a
      consistent theoretical basis which is mandatory for systems containing heavy
      elements. A PtF6(2-) gas phase photoelectron spectrum is not yet available and
      our calculations therefore have predictive character. As it is characteristic for
      dianionic systems a strong dependence on basis set size and molecular geometry is
      observed. In contrast to the already calculated PtCl(6)2- photoelectron spectrum
      no valence orbital inversion due to strong interplay of spin-orbit coupling and
      electron correlation is observed. Furthermore an unusually strong spin-orbit
      splitting was found for the sigma-type subvalence 1t1u molecular spinor despite
      its very small platinum p population. The double ionization threshold is strongly
      lowered by relativistic effects now enabling an interatomic Coulombic decay
      process after ionization from the sigma-bonding orbitals. The results stress the
      importance of spin-orbit coupling for the understanding of the spectral structure
      which cannot be reproduced by a scalar-relativistic treatment only.

PMID- 17444716
TI  - Ab initio study of hydrated potassium halides KX(H2O)1-6 (X=F,Cl,Br,I).
AB  - The ionic dissociation of salts was examined with a theoretical study of KX
      (X=F,Cl,Br,I) hydrated by up to six water molecules KX(H2O)n (n=1-6).
      Calculations were done using the density functional theory and second order
      Moller-Plesset (MP2) perturbational theory. To provide more conclusive results,
      single point energy calculations using the coupled cluster theory with single,
      double, and perturbative triple excitations were performed on the MP2 optimized
      geometries. The dissociation feature of the salts was examined in terms of K-X
      bond lengths and K-X stretch frequencies. In general, the successive
      incorporation of water molecules to the cluster lengthens the K-X distance, and
      consequently the corresponding frequency decreases. Near 0 K, the KX salt ion
      pairs can be partly separated by more than five water molecules. The
      pentahydrated KX salt is partly dissociated, though these partly dissociated
      structures are almost isoenergetic to the undissociated ones for KFKCl. For the
      hexahydrated complexes, KF is undissociated, KClKBr is partly dissociated, and KI
      is dissociated (though this dissociated structure is nearly isoenergetic to a
      partly dissociated one). On the other hand, at room temperature, the penta- and
      hexahydrated undissociated structures which have less hydrogen bonds are likely
      to be more stable than the partly dissociated ones because of the entropy effect.
      Therefore, the dissociation at room temperature could take place for higher
      clusters than the hexahydrated ones.

PMID- 17444717
TI  - Effect of different sodium halides on the self-association of tertiary butanol in
      water.
AB  - The molecular self-association of hydrophobic substances is an important process
      for many biological systems. Here, the authors study the effect of salt on the
      molecular self-association of t-butanol in water solution, using NMR techniques.
      They compare the effects of different sodium halides (NaCl, NaBr, and NaI) as a
      function of their concentration.

PMID- 17444718
TI  - Optimized molecular force field for sulfur hexafluoride simulations.
AB  - An optimized molecular force field for sulfur hexafluoride (SF6) simulations is
      presented in this work. The new force field for SF6 contains two parts: a Lennard
      Jones potential that deals with F-F intermolecular interactions and the second
      term dealing with the intramolecular forces. In this second part the flexibility
      of the molecule is explicitly considered by 6 harmonic stretch terms, modeling
      the S-F chemical bonds, and 12 harmonic bending terms, modeling the F-S-F angular
      deformations. The parameters of the new force field have been obtained by a
      multivariable optimization procedure, whose main feature is the simultaneous
      fitting of all force field parameters, using as reference data several
      equilibrium properties (vapor pressure, saturated liquid density, and surface
      tension) and shear viscosity. The new force field clearly improves the
      description of the phase envelope and the rest of the properties as compared to
      previous simulations for a rigid model for the same molecule [A. Olivet et al.,
      J. Chem. Phys. 123, 194508 (2005)]. Results for the optimized force field
      concerning the vapor-liquid coexistence curve, several thermodynamics states at
      the homogeneous gas and liquid region, and transport coefficients of SF6 are in
      good agreement with available experimental data.

PMID- 17444719
TI  - Geometry optimization based on linear response free energy with quantum
      mechanical/molecular mechanical method: applications to Menshutkin-type and
      Claisen rearrangement reactions in aqueous solution.
AB  - The authors present a method based on a linear response theory that allows one to
      optimize the geometries of quantum mechanical/molecular mechanical (QM/MM)
      systems on the free energy surfaces. Two different forms of linear response free
      energy functionals are introduced, and electronic wave functions of the QM
      region, as well as the responses of electrostatic and Lennard-Jones potentials
      between QM and MM regions, are self-consistently determined. The covariant matrix
      relating the QM charge distribution to the MM response is evaluated by molecular
      dynamics (MD) simulation of the MM system. The free energy gradients with respect
      to the QM atomic coordinates are also calculated using the MD trajectory results.
      They apply the present method to calculate the free energy profiles of Menshutkin
      type reaction of NH3 with CH3Cl and Claisen rearrangement of allyl vinyl ether in
      aqueous solution. For the Menshutkin reaction, the free energy profile calculated
      with the modified linear response free energy functional is in good agreement
      with that by the free energy perturbation calculations. They examine the
      nonequilibrium solvation effect on the transmission coefficient and the kinetic
      isotope effect for the Claisen rearrangement.

PMID- 17444720
TI  - Complete thermodynamically consistent kinetic model of particle nucleation and
      growth: numerical study of the applicability of the classical theory of
      homogeneous nucleation.
AB  - A complete thermodynamically consistent elementary reaction kinetic model of
      particle nucleation and growth from supersaturated vapor was developed and
      numerically evaluated to determine the conditions for the steady-state regime.
      The model treats all processes recognized in the aerosol science (such as
      nucleation, condensation, evaporation, agglomerationcoagulation, etc.) as
      reversible elementary reactions. It includes all possible forward reactions
      (i.e., of monomers, dimers, trimers, etc.) together with the thermodynamically
      consistent reverse processes. The model is built based on the Kelvin
      approximation, and has two dimensionless parameters: S0-the initial
      supersaturation and Theta-the dimensionless surface tension. The time evolution
      of the size distribution function was obtained over the ranges of parameters S0
      and Theta. At low initial supersaturations, S0, the steady state is established
      after a delay, and the steady-state distribution function corresponds to the
      predictions of the classical nucleation theory. At high initial supersaturations,
      the depletion of monomers due to condensation on large clusters starts before the
      establishing of the steady state. The steady state is never reached, and the
      classical nucleation theory is not applicable. The boundary that separates these
      two regimes in the two dimensionless parameter space, S0 and Theta, was
      determined. The model was applied to several experiments on water nucleation in
      an expansion chamber [J. Wolk and R. Strey, J. Phys. Chem. B 105, 11683 (2001)]
      and in Laval nozzle [Y. J. Kim et al., J. Phys. Chem. A 108, 4365 (2004)]. The
      conditions of the experiments performed using Laval nozzle (S0=40-120) were found
      to be close to the boundary of the non-steady-state regime. Additional
      calculations have shown that in the non-steady-state regime the nucleation rate
      is sensitive to the rate constants of the initial steps of the nucleation
      process, such as the monomer-monomer, monomer-dimer, etc., reactions. This
      conclusion is particularly important for nucleation from supersaturated water
      vapor, since these processes for water molecules at and below the atmospheric
      pressure are in the low pressure limit, and the rate constants can be several
      orders of magnitude lower than the gas kinetic. In addition, the impact of the
      thermodynamic inconsistency of the previously developed partially reversible
      kinetic numerical models was assessed. At typical experimental conditions for
      water nucleation, S0=10 and Theta=10 (T=250 K), the error in the particle
      nucleation rate introduced by the thermodynamic inconsistency exceeds one order
      of magnitude.

PMID- 17444721
TI  - Theoretical study on the sound absorption of electrolytic solutions. I.
      Theoretical formulation.
AB  - A theory is formulated that describes the sound absorption of electrolytic
      solutions due to the relative motion of ions, including the formation of ion
      pairs. The theory is based on the Kubo-Green formula for the bulk viscosity. The
      time correlation function of the pressure is projected onto the bilinear product
      of the density modes of ions. The time development of the product of density
      modes is described by the diffusive limit of the generalized Langevin equation,
      and approximate expressions for the three- and four-body correlation functions
      required are given with the hypernetted-chain integral equation theory.
      Calculations on the aqueous solutions of model electrolytes are performed. It is
      demonstrated that the theory describes both the activated barrier crossing
      between contact and solvent-separated ion pairs and the Coulombic correlation
      between ions.

PMID- 17444722
TI  - Effect of physical aging on the Johari-Goldstein and alpha relaxations of D
      sorbitol: a study by thermally stimulated depolarization currents.
AB  - The relaxations in amorphous D-sorbitol have been studied by thermally stimulated
      depolarization currents during annealing at 255 K, which is 17 K below its
      calorimetric glass transition temperature Tg=272 K. As the glass structurally
      relaxes on aging, the features of the alpha relaxation and of the Johari
      Goldstein (JG) relaxation change with time. For the alpha relaxation (i) the
      dielectric strength decreases; (ii) the activation energy decreases; and (iii)
      the relaxation time increases. For the JG relaxation the dielectric strength also
      decreases but with a different time dependence, and there is no evidence for any
      modification of the kinetic features of the mobility. The amplitude of response
      to aging is higher for the higher temperature motional components of the Johari
      Goldstein relaxation compared with the lower temperature ones.

PMID- 17444723
TI  - Competition effects in diffusion-controlled bulk reactions between ions.
AB  - A numerical solution for competitive diffusion into two static charged sinks is
      presented and compared against an approximate analytical solution. It is shown
      that for an attractive Coulomb potential the correction to the total diffusive
      flux of ionic reactants due to diffusion interaction between sinks may be ignored
      for large enough values of the Onsager length and thus the reaction rate can be
      described by the classical Debye formula. On the other hand, for repulsive
      potentials the competition becomes more profound than in the case of uncharged
      sinks. However, this effect is of little interest because of a small value of the
      diffusive flux on the reaction surface.

PMID- 17444724
TI  - Integral equation study of hydrophobic interaction: a comparison between the
      simple point charge model for water and a Lennard-Jones model for solvent.
AB  - The hydrophobic interaction that is characterized by a potential of mean force
      (PMF) between spherical apolar solutes immersed in the simple point charge (SPCE)
      model for water was studied using an interaction site model integral equation
      based on a density-functional theory for molecular fluids. For comparison with
      the PMFs for various size solutes in the SPCE model, the PMFs in a Lennard-Jones
      (LJ) model for a solvent whose diameter is same as the SPCE model were also
      studied using a hypernetted chain integral equation. It is noted in the LJ model
      that the hydrogen bond and its network structure are completely ignored, but the
      translational entropy is taken into account. Both PMFs obtained from the SPCE
      model and from the LJ model have a large first minimum at a contact distance of
      solutes. In the case that the solute size is about three times larger than water,
      these PMFs also have a large maximum at a longer distance than the contact
      position. The strong attraction is attributed to the translational entropy of the
      solvent, and that the large activation barrier is arising from the weak
      attraction between the solute and the solvent. The comparison between the SPCE
      model and the LJ solvent model suggests that the qualitative description of the
      hydrophobic interaction is possible by using the LJ solvent model. On the other
      hand, the dewetting tendency on the surface of the apolar solute in a room
      condition is observed only on the SPCE model. These results indicate that the
      characteristics of water such as the hydrogen bond affect rather the hydrophobic
      hydration than the hydrophobic interaction.

PMID- 17444725
TI  - Representability problems for coarse-grained water potentials.
AB  - The use of an effective intermolecular potential often involves a compromise
      between more accurate, complex functional forms and more tractable simple
      representations. To study this choice in detail, we systematically derive coarse
      grained isotropic pair potentials that accurately reproduce the oxygen-oxygen
      radial distribution function of the TIP4P-Ew water model at state points over
      density ranges from 0.88 to 1.30 g/cm3 and temperature ranges from 235 to 310 K.
      Although by construction these effective potentials correctly represent the
      isothermal compressibility of TIP4P-Ew water, they do not accurately resolve
      other thermodynamic properties such as the virial pressure, the internal energy,
      or thermodynamic anomalies. Because at a given state point the pair potential
      that reproduces the pair structure is unique, we have therefore explicitly
      demonstrated that it is impossible to simultaneously represent the pair structure
      and several key equilibrium thermodynamic properties of water with state-point
      dependent radially symmetric pair potentials. We argue that such representability
      problems are related to, but different from, more widely acknowledged
      transferability problems and discuss in detail the implications this has for the
      modeling of water and other liquids by coarse-grained potentials. Nevertheless,
      regardless of thermodynamic inconsistencies, the state-point dependent effective
      potentials for water do generate structural and dynamical anomalies.

PMID- 17444726
TI  - Further studies of a simple atomistic model of silica: thermodynamic stability of
      zeolite frameworks as silica polymorphs.
AB  - We have applied our previously reported model of silica based on low coordination
      and strong association [J. Chem. Phys. 121, 8415 (2004)], to the calculation of
      phase stability of zeolite frameworks SOD, LTA, MFI, and FAU as silica
      polymorphs. We applied the method of Frenkel and Ladd for calculating free
      energies of these solids. Our model predicts that the MFI framework structure has
      a regime of thermodynamic stability at low pressures and above approximately 1400
      K, relative to dense phases such as quartz. In contrast, our calculations predict
      that the less dense frameworks SOD, LTA, and FAU exhibit no regime of
      thermodynamic stability. We have also used our model to investigate whether
      templating extends the MFI regime of thermodynamic stability to lower
      temperatures, by considering templates with hard-sphere repulsions and mean-field
      attractions to silica. Within the assumptions of our model, we find that quartz
      remains the thermodynamically stable polymorph at zeolite synthesis temperatures
      (approximately 400 K) unless unphysically large template-silica attractions are
      assumed. These predictions suggest that some zeolites such as MFI may have
      regimes of thermodynamic stability even without template stabilization.

PMID- 17444727
TI  - Edge effects in an electrochemical reaction: HCOOH oxidation on a Pt ribbon.
AB  - The use of a ribbon-shaped Pt electrode gives rise to edge effects of the
      interfacial potential, as is predicted from the potential theory in the form of
      the corresponding reaction-migration equation. They are studied in the bistable
      region of formic acid oxidation. Essentially, the edges tend to be more passive
      than the bulk of the electrode, which also causes a passivation (activation)
      transition to originate from the edges (center) of the ribbon. The experimental
      results are in agreement with simulations of the reaction-migration system.

PMID- 17444728
TI  - Energy level alignment at metal/organic semiconductor interfaces: "pillow"
      effect, induced density of interface states, and charge neutrality level.
AB  - A unified model, embodying the "pillow" effect and the induced density of
      interface states (IDIS) model, is presented for describing the level alignment at
      a metal/organic interface. The pillow effect, which originates from the
      orthogonalization of the metal and organic wave functions, is calculated using a
      many-body linear combination of atomic orbitals Hamiltonian, whereby electron
      long-range interactions are obtained using an expansion in the metal/organic wave
      function overlap, while the electronic charge of both materials remains
      unchanged. This approach yields the pillow dipole and represents the first effect
      induced by the metal/organic interaction, resulting in a reduction of the metal
      work function. In a second step, we consider how charge is transferred between
      the metal and the organic material by means of the IDIS model: Charge transfer is
      determined by the relative position of the metal work function (corrected by the
      pillow effect) and the organic charge neutrality level, as well as by an
      interface parameter S, which measures how this potential difference is screened.
      In our approach, we show that the combined IDIS-pillow effects can be described
      in terms of the original IDIS alignment corrected by a screened pillow dipole.
      For the organic materials considered in this paper, we see that the IDIS dipole
      already represents most of the realignment induced at the metal/organic
      interface. We therefore conclude that the pillow effect yields minor corrections
      to the IDIS model.

PMID- 17444729
TI  - Effect of curvature and chirality for hydrogen storage in single-walled carbon
      nanotubes: a combined ab initio and Monte Carlo investigation.
AB  - Combined ab initio and grand canonical Monte Carlo simulations have been
      performed to investigate the dependence of hydrogen storage in single-walled
      carbon nanotubes (SWCNTs) on both tube curvature and chirality. The ab initio
      calculations at the density functional level of theory can provide useful
      information about the nature of hydrogen adsorption in SWCNT selected sites and
      the binding under different curvatures and chiralities of the tube walls. Further
      to this, the grand canonical Monte Carlo atomistic simulation technique can model
      large-scale nanotube systems with different curvature and chiralities and
      reproduce their storage capacity by calculating the weight percentage of the
      adsorbed material (gravimetric density) under thermodynamic conditions of
      interest. The author's results have shown that with both computational
      techniques, the nanotube's curvature plays an important role in the storage
      process while the chirality of the tube plays none.

PMID- 17444730
TI  - Local and semilocal density functional computations for crystals of 1-alkyl-3
      methyl-imidazolium salts.
AB  - The accuracy and reliability of popular density functional approximations for the
      compounds giving origin to room temperature ionic liquids have been assessed by
      computing the T=0 K crystal structure of several 1-alkyl-3-methyl-imidazolium
      salts. Two prototypical exchange-correlation approximations have been considered,
      i.e., the local density approximation (LDA) and one gradient corrected scheme
      [PBE-GGA, Phys. Rev. Lett. 77, 3865 (1996)]. Comparison with low-temperature x
      ray diffraction data shows that the equilibrium volume predicted by either
      approximations is affected by large errors, nearly equal in magnitude
      (approximately 10%), and of opposite sign. In both cases the error can be traced
      to a poor description of the intermolecular interactions, while the
      intramolecular structure is fairly well reproduced by LDA and PBE-GGA. The PBE
      GGA optimization of atomic positions within the experimental unit cell provides
      results in good agreement with the x-ray structure. The correct system volume can
      also be restored by supplementing PBE-GGA with empirical dispersion terms
      reproducing the r-6 attractive tail of the van der Waals interactions.

PMID- 17444731
TI  - Local linear viscoelasticity of confined fluids.
AB  - In this paper the authors propose a novel method to study the local linear
      viscoelasticity of fluids confined between two walls. The method is based on the
      linear constitutive equation and provides details about the real and imaginary
      parts of the local complex viscosity. They apply the method to a simple atomic
      fluid undergoing zero mean oscillatory flow using nonequilibrium molecular
      dynamics simulations. The method shows that the viscoelastic properties of the
      fluid exhibit dramatic spatial changes near the wall-fluid boundary due to the
      high density in this region. It is also shown that the real part of the viscosity
      converges to the frequency dependent local shear viscosity sufficiently far away
      from the wall. This also provides valuable information about the transport
      properties in the fluid, in general. The viscosity is compared with predictions
      from the local average density model. The two methods disagree in that the local
      average density model predicts larger viscosity variations near the wall-fluid
      boundary than what is observed through the method presented here.

PMID- 17444732
TI  - Molecular dynamics simulations of stretched gold nanowires: the relative utility
      of different semiempirical potentials.
AB  - The mechanical elongation of a finite gold nanowire has been studied by molecular
      dynamics simulations using different semiempirical potentials for transition
      metals. These potentials have been widely used to study the mechanical properties
      of finite metal clusters. Combining with density functional theory calculations
      along several atomic-configuration trajectories predicted by different
      semiempirical potentials, the authors conclude that the second-moment
      approximation of the tight-binding scheme (TB-SMA) potential is the most suitable
      one to describe the energetics of finite Au clusters. They find that for the
      selected geometries of Au wires studied in this work, the ductile elongation of
      Au nanowires along the [001] direction predicted by the TB-SMA potential is
      largely independent of temperature in the range of 0.01-298 K. The elongation
      leads to the formation of monatomic chains, as has been observed experimentally.
      The calculated force-versus-elongation curve is remarkably consistent with
      available experimental results.

PMID- 17444733
TI  - Plasmon modes of curvilinear metallic core/shell particles.
AB  - The plasmon hybridization method is generalized to calculate the plasmon modes
      and optical properties of solid and dielectric-core/metallic-shell particles of
      geometrical structures that can be described using separable curvilinear
      coordinates. The authors present a detailed discussion of the plasmonic
      properties of hollow metallic nanowires with dielectric cores and core/shell
      structures of oblate and prolate spheroidal shapes. They show that the plasmon
      frequencies of these particles can be expressed in a common form and that the
      plasmon modes of the core/shell structures can be viewed as resulting from the
      hybridization of the solid particle plasmons associated with the outer surface of
      the shell and of the cavity plasmons associated with the inner surface.

PMID- 17444734
TI  - Chiral separation on a model adsorbent with periodic surface heterogeneity.
AB  - Optimization of enantioselectivity in heterogeneous catalysis and chiral
      chromatography is a challenging task for the production of enantiopure chemicals.
      Enantioselective adsorbents usually consist of a surface with chiral receptors
      being either chiral molecules linked to the surface or chiral pockets formed by
      molecular templating of the surface. In both cases, the enantioselectivity is
      controlled mainly by the strength of the receptor-enantiomer interaction, such
      that one-to-one correspondence is usually preserved. The authors use Monte Carlo
      calculations to show that this steric requirement is not a necessary condition
      for the effective separation of chiral molecules. In particular, they propose a
      way in which a chiral surface can be constructed by a suitable spatial
      distribution of active sites for which the classical concept of a chiral receptor
      is no longer useful. Their calculations indicate that the effectiveness of the
      separation is affected mainly by the difference in shape of the adsorption energy
      distribution functions corresponding to the enantiomers.

PMID- 17444735
TI  - Electron and hole mobilities in polymorphs of benzene and naphthalene: role of
      intermolecular interactions.
AB  - The hole and electron mobilities of the polymorphs of benzene and naphthalene
      crystals are estimated through quantum chemical calculations. The reorganization
      energy (lambda) and the charge-transfer matrix elements (Hmn) calculated for the
      two molecules reveal that these crystals can be used for dual applications, for
      both hole and electron conductance. The electron mobilities are five to eight
      times more than the hole mobilities for benzene while for naphthalene, the hole
      mobilities are almost an order magnitude more than the electron mobilities. The
      transfer matrices for both hole and electron conductance decrease monotonically
      with increase in the intermolecular distances. Calculations for various unique
      stacked dimers as determined from the radial distribution functions in both the
      crystals for the two molecules show strong dependence on the orientations of the
      rings and for similar intermolecular separations; Hmnhole is larger than
      Hmnelectron. The crystal mobilities are calculated from the weighted average over
      all the unique pair of molecules. The overall preference in a crystal for hole or
      electron mobility depends on the mutual competition of lambdahole/lambdaelectron
      and Hmnhole/Hmnelectron. From our microscopic understanding of essential
      parameters, specific dimers are identified from the crystalline solids of the two
      polymorphs and experimental strategies are suggested to enrich such pairs in
      aggregates for enhancing mobilities for these organic solids.

PMID- 17444736
TI  - Nonequilibrium molecular dynamics simulation to describe the rotation of rigid,
      low aspect ratio carbon nanotubes in simple shear flow.
AB  - In this paper, the rotation of short carbon nanotubes in simple shear liquid
      argon flow was investigated by nonequilibrium molecular dynamics (MD) simulation.
      In their simulations, nanotubes were described as rigid cylinders of carbon
      atoms. Lennard-Jones potential was employed to represent both argon-argon and
      argon-carbon interactions. Results show that time period of a nanotube as
      calculated from MD simulations is longer than what would be calculated from
      Jeffery's equation based on the aspect ratio of the cylinder. The difference is
      much higher at low shear rates and for small aspect ratios. Results also reveal
      that adding caps to an open-ended nanotube speeds up its rotation.

PMID- 17444737
TI  - Continuum theory of polymer crystallization.
AB  - We present a kinetic model of crystal growth of polymers of finite molecular
      weight. Experiments help to classify polymer crystallization broadly into two
      kinetic regimes. One is observed in melts or in high molar mass polymer solutions
      and is dominated by nucleation control with G approximately exp(1/TDeltaT), where
      G is the growth rate and DeltaT is the supercooling. The other is observed in low
      molar mass solutions (as well as for small molecules) and is diffusion controlled
      with G approximately DeltaT, for small DeltaT. Our model unifies these two
      regimes in a single formalism. The model accounts for the accumulation of polymer
      chains near the growth front and invokes an entropic barrier theory to recover
      both limits of nucleation and diffusion control. The basic theory applies to both
      melts and solutions, and we numerically calculate the growth details of a single
      crystal in a dilute solution. The effects of molecular weight and concentration
      are also determined considering conventional polymer dynamics. Our theory shows
      that entropic considerations, in addition to the traditional energetic arguments,
      can capture general trends of a vast range of phenomenology. Unifying ideas on
      crystallization from small molecules and from flexible polymer chains emerge from
      our theory.

PMID- 17444738
TI  - Glass transition in an isostatically compressed calcium metaphosphate glass.
AB  - The authors report an ambient-pressure differential scanning calorimetric study
      of a calcium metaphosphate glass that has been isostatically compressed slightly
      above its glass transition temperature and was frozen-in under pressure. It is
      shown that the enthalpy overshoot of the calorimetric glass transition is
      enhanced by this treatment. This enhancement is associated with a decrease in the
      apparent fictive temperature TfA that is determined using the enthalpy-matching
      approach. The origin of this correlation is discussed.

PMID- 17444739
TI  - Computer simulation on the collision-sticking dynamics of two colloidal particles
      in an optical trap.
AB  - Collisions of a particle pair induced by optical tweezers have been employed to
      study colloidal stability. In order to deepen insights regarding the collision
      sticking dynamics of a particle pair in the optical trap that were observed in
      experimental approaches at the particle level, the authors carry out a Brownian
      dynamics simulation. In the simulation, various contributing factors, including
      the Derjaguin-Landau-Verwey-Overbeek interaction of particles, hydrodynamic
      interactions, optical trapping forces on the two particles, and the Brownian
      motion, were all taken into account. The simulation reproduces the tendencies of
      the accumulated sticking probability during the trapping duration for the trapped
      particle pair described in our previous study and provides an explanation for why
      the two entangled particles in the trap experience two different statuses.

PMID- 17444740
TI  - Potential distribution theorem for the polymer-induced depletion between
      colloidal particles.
AB  - The authors investigated the polymer-mediated colloidal interactions in a good
      solvent wherein the particle size varies from that much smaller than the polymer
      radius of gyration up to macroscopic and the polymer concentration varies from
      that corresponding to a dilute solution to that close to a melt. At conditions
      directly accessible to molecular simulations, the theoretical predictions agree
      favorably with the simulation results for the distributions of polymer segments
      and for the polymer-mediated colloidal interactions. The theoretical methods were
      then exploited to examine the polymer structure and colloidal interactions when
      the particle/polymer size ratio changes from the "protein" limit to the "colloid"
      limit at different regimes of the polymer concentration (i.e., dilute,
      semidilute, and concentrated). The authors found that the surface curvature plays
      a significant role on the distribution of polymer segments near the particle
      surface at low polymer concentration, but this effect diminishes as the polymer
      concentration increases. The Derjaguin approximation works reasonably well at
      high polymer concentration even in the protein limit, but it may fail
      qualitatively at low polymer concentration where the polymer-induced colloidal
      force becomes long range.

PMID- 17444741
TI  - Surface segregation and surface tension of polydisperse polymer melts.
AB  - The effect of polydispersity on surface segregation of a lower molecular weight
      polymer component in a higher molecular weight linear polymer melt host is
      investigated theoretically. We show that the integrated surface excess zM of a
      polymer component of molecular weight M satisfies a simple relation zM=2Ue(M/Mw
      1)phiM, where Mw is the weight averaged molecular weight, phiM is the polymer
      volume fraction, and Ue is the attraction of polymer chain ends to the surface.
      Ue is principally of entropic origin, but also reflects any energetic preference
      of chain ends to the surface. We further show that the surface tension gammaM of
      a polydisperse melt of high molar mass components depends on the number average
      degree of polymerization Mn as, gammaM=gammainfinity+2UerhobRT/Mn. The parameter
      gammainfinity is the asymptotic surface tension of an infinitely long polymer of
      the same chemistry, rhob is the bulk density of the polymer, R is the universal
      gas constant, and T is the temperature. The predicted gammaM compare favorably
      with surface tension values obtained from self-consistent field theory
      simulations that include equation of state effects, which account for changes in
      polymer density with molecular weight. We also compare the predicted surface
      tension with available experimental data.

PMID- 17444742
TI  - Coil-globule transition of a single short polymer chain: an exact enumeration
      study.
AB  - The authors present an exact enumeration study of short self-avoiding walks in
      two as well as in three dimensions that addresses the question, "what is the
      shortest walk for which the existence of all the three scaling regimes--coil,
      globule, and the theta--could be demonstrated." Even though they could easily
      demonstrate the coil and the globule phase from free energy considerations, they
      could demonstrate the existence of a theta temperature only by using a scaling
      form for the distribution of gyration radius. That even such short walks have a
      scaling behavior is an unexpected result of this work.

PMID- 17444743
TI  - Structural and dynamical properties for confined polymers undergoing planar
      Poiseuille flow.
AB  - The authors present the results from nonequilibrium molecular dynamics
      simulations for the structural and dynamical properties of highly confined linear
      polymer fluids undergoing planar Poiseuille flow. They study systems confined
      within pores of several atomic diameters in width and investigate the dependence
      of the density profiles, the mean squared radius of gyration, the mean squared
      end-to-end distance, streaming velocity, strain rate, shear stress, and streaming
      angular velocity as functions of average fluid density and chain length. Their
      simulation results show that, sufficiently far from the walls, the radius of
      gyration for molecules under shear in the middle of the pore follows the power
      law Rg=ANbnu, where Nb is the number of bonds and the exponent has a value of 0.5
      which resembles the value for a homogeneous equilibrium fluid. Under the
      conditions simulated, the authors find the onset of flat velocity profiles but
      with very little wall slippage. These flat profiles are most likely due to the
      restricted layering of the fluid into just one or two molecular layers for narrow
      pore widths compared to chain length, rather than typical plug-flow conditions.
      The angular velocity is shown to be proportional to half the strain rate in the
      pore interior when the chain length is sufficiently small compared to the pore
      width, consistent with the behavior for homogeneous fluids in the linear regime.

PMID- 17444744
TI  - Phase separation in polyisoprene/polystyrene blends by a systematically coarse
      grained model.
AB  - The authors have successfully developed a structurally coarse-grained 1,4-cis
      polyisoprene-atactic polystyrene blend model by systematic mapping between a
      detailed atomistic model and a mesoscale model. This is to their best knowledge
      the first time that a chemically specific polymer blend model has been used to
      study the phase separation morphology and kinetics in a blend. A structurally
      optimized force-field model has many advantages over simple bead-spring models in
      terms of representing the chain microstructure. It keeps the identity of the
      polymers, particularly the structure through radial distribution functions.
      Starting from randomly mixed initial configurations, the blends show a clear
      phase separation for chain lengths around 10 monomers and this separation becomes
      more pronounced with the increase of chain length. The ensuing morphology is
      lamellar at equiweight concentrations and cylindrical or spherical at unbalanced
      concentrations. Morphologies are validated to be stable under increasing system
      sizes and further characterized quantitatively by density profiles.

PMID- 17444745
TI  - Dynamics of free chains in polymer nanocomposites.
AB  - The dynamics of entangled polymeric chains in a polymer filled with nanoparticles
      is studied by means of molecular dynamics simulations of a model system. The
      primary objective is to study to what extent the reptation of polymers not in
      direct contact with fillers is modified with respect to the neat material. To
      this end, two systems are considered: A regular filled material in which the
      filler-polymer affinity is controlled, and a system in which the beads in contact
      with the filler at the beginning of the production phase of the simulation are
      tethered to the filler surface. This second system represents the limit case of
      long polymer-filler attachment time. In this case attention is focused on the
      free chains of the melt. The dynamics in the two models is different. In the
      filled system uniform slowing down for all Rouse modes is observed. The effect
      varies monotonically with the filler-polymer affinity. Up to saturation, this
      behavior may be captured by usual models with an effective, affinity-dependent,
      friction coefficient. In the system with grafted chains, the free chain Rouse
      dynamics is identical to that in the neat material, except for the longest modes
      which are significantly slowed down. More interestingly, the dynamics of the free
      chains depends in a nonmonotonic way on the polymer-filler affinity, although the
      free chains do not come in direct contact with the filler. This effect is due to
      small changes in the structure of the polydisperse brush upon modification of the
      affinity. Specifically, the density of the brush and the amount of
      interpenetration of free and grafted chains depend on the filler-polymer
      affinity. The use of a reptation model with modified tube diameter to capture
      this behavior is discussed.

PMID- 17444746
TI  - Driven polymer transport through a nanopore controlled by a rotating electric
      field: off-lattice computer simulations.
AB  - The driven translocation kinetics of a single strand polynucleotide chain through
      a nanopore is studied using off-lattice Monte Carlo simulations, by which the
      authors demonstrate a novel method in controlling the driven polymer transport
      through a nanopore by a rotating electric field. The recorded time series of
      blockade current from the driven polynucleotide transport are used to determine
      the sequence of polynucleotides by implementing a modified Monte Carlo algorithm,
      in which the energy landscape paving technique is incorporated to avoid trapping
      at deep local minima. It is found that only six-time series of block current are
      required to completely determine the polynucleotide sequence if the average
      missing rate (AMR) of current signals in these time series is smaller than 20%.
      For those time series with AMR greater than 20%, the error rate in sequencing an
      unknown polynucleotide decreases rapidly by increasing the number of time series.
      To find the most appropriate experimental conditions, the authors have
      investigated the dependence of AMR of current signals and qualified rate of
      measured time series of blockade current on various controllable experimental
      variables.

PMID- 17444747
TI  - Structure and aggregation of a helix-forming polymer.
AB  - We have studied the competition between helix formation and aggregation for a
      simple polymer model. We present simulation results for a system of two such
      polymers, examining the potential of mean force, the balance between
      intermolecular and intramolecular interactions, and the promotion or disruption
      of secondary structure brought on by the proximity of the two molecules. In
      particular, we demonstrate that proximity between two such molecules can
      stabilize secondary structure. However, for this model, observed secondary
      structure is not stable enough to prevent collapse of the system into an
      unstructured globule.

PMID- 17444748
TI  - Density functional theory for a primitive model of nanoparticle-block copolymer
      mixtures.
AB  - Amphiphilic block copolymers provide useful templates for fabrication of
      nanostructured materials that are appealing for a wide variety of applications.
      The preparation of polymer-particle hybrid materials requires a good
      understanding of the chemical nature and topology of the amphiphilic molecules as
      well as their interactions with the embedded nanoparticles. This article reports
      a density functional theory (DFT) for a coarse-grained model of block copolymer
      nanoparticle mixtures that is able to account for the properties of particles and
      copolymers within a self-consistent framework. It predicts various well-organized
      structures that can be effectively controlled by adjusting the polymer chain
      length and polymer-particle interactions. Illustrative examples based on
      relatively short chains suggest that, in qualitative agreement with experiments,
      large particles tend to be excluded from a polymer brush near a solid substrate,
      whereas smaller particles may be dissolved. The DFT is able to capture the
      dispersion of large particles in the microdomain of block copolymer that is
      energetically favorable, but localization of smaller particles at the microdomain
      interfaces.

PMID- 17444749
TI  - Mean field theory for the intermolecular and intramolecular conformational
      transitions of a single flexible polyelectrolyte chain.
AB  - The diMarzio theory has been extended to elucidate the intermolecular and
      intramolecular phase segregations of a single flexible chain polyelectrolyte in
      dilute salt-free solutions. At the long chain limit, this theory yields the
      formalism obtained from the more sophisticated Edward Hamiltonian for
      polyelectrolyte problems. The calculated phase diagram exhibits the features of a
      first-order phase transition, with continuous and discontinuous transitions
      separated by a critical point. Under the discontinuous transition, the
      polyelectrolyte chain exhibits coexistent expanded and collapsed conformational
      states, same as intermolecular phase segregation. For a limiting long chain, the
      mean chain size at critical point is roughly 90% of the size of an ideal chain.
      Such a result implies that partial contraction within a chain molecule is
      required to collapse a flexible polyelectrolyte chain. Moreover, the theory
      predicts that for a longer chain, intramolecular segregated conformations differ
      significantly from intermolecular segregated conformations, but the difference
      becomes small for shorter chains. Besides, the charge needed to induce
      intramolecular segregation is smaller than that of intermolecular segregation for
      a given chain length. These findings are consistent with previous literature
      results.

PMID- 17444750
TI  - Heteropolymer translocation through nanopores.
AB  - The authors investigate the translocation dynamics of heteropolymers driven
      through a nanopore using a constant temperature Langevin thermostat.
      Specifically, they consider heteropolymers consisting of two types of monomers
      labeled A and B, which are distinguished by the magnitude of the driving force
      that they experience inside the pore. From a series of studies on polymers with
      sequences AmBn the authors identify both universal as well as specific sequence
      properties of the translocating chains. They find that the scaling of the average
      translocation time as a function of the chain length N remains unaffected by the
      heterogeneity, while the residence time of each bead is a strong function of the
      sequence for short repeat units. They further discover that for a symmetric
      heteropolymer AnBn of fixed length, the pattern exhibited by the residence times
      of the individual monomers has striking similarity with a double slit
      interference pattern where the total number of repeat units N/2n controls the
      number of interference fringes. These results are relevant for designing nanopore
      based sequencing techniques.

PMID- 17444751
TI  - Vibrational dynamics of DNA: IV. Vibrational spectroscopic characteristics of A-,
      B-, and Z-form DNA's.
AB  - Linear and nonlinear IR spectroscopic studies of nucleic acids can provide
      crucial information on solution conformations of DNA double helix and its complex
      with other molecules. Carrying out density functional theory calculations of A-,
      B-, and Z-form DNA's, the authors obtained vibrational spectroscopic properties
      as well as coupling constants between different basis modes. The vibrational
      couplings that determine the extent of exciton delocalization are strongly
      dependent on DNA conformation mainly because the interlayer distance between two
      neighboring base pairs changes with respect to the DNA conformation. The Z-DNA
      has comparatively small interlayer vibrational coupling constants so that its
      vibrational spectrum depends little on the number of base pairs, whereas the A
      DNA shows a notable dependency on the size. Furthermore, it is shown that a few
      distinctively different line shape changes in both IR and two-dimensional IR
      spectra as the DNA conformation changes from B to A or from B to Z can be used as
      marker bands and characteristic features distinguishing different DNA
      conformations.

PMID- 17444752
TI  - Random sequences with power-law correlations exhibit proteinlike behavior.
AB  - We use a replica approach to investigate the thermodynamic properties of the
      random heteropolymers with persistent power-law correlations in monomer sequence.
      We show that this type of sequences possess proteinlike properties. In
      particular, we show that they can fold into stable unique three-dimensional
      structure (the "native" structure, in protein terminology) through two different
      types of pathways. One is a fast folding pathway and leads directly to the native
      structure. Another one, a more slower pathway, passes through the microphase
      separated (MPS) state and includes a number of intermediate glassy states. The
      scale and the magnitude of the MPS are calculated. The frozen state can be
      reached only by sequences with weak long-range correlations. The critical value
      for the correlation exponent is found, above which (strong correlations) freezing
      is impossible.

PMID- 17444753
TI  - Extending molecular dynamics time scales with milestoning: example of complex
      kinetics in a solvated peptide.
AB  - A recently introduced computational algorithm to extend time scales of atomically
      detailed simulations is illustrated. The algorithm, milestoning, is based on
      partitioning the dynamics to a sequence of trajectories between "milestones" and
      constructing a non-Markovian model for the motion along a reaction coordinate.
      The kinetics of a conformational transition in a blocked alanine is computed and
      shown to be accurate, more efficient than straightforward molecular dynamics by a
      factor of about 9, and nonexponential. A general scaling argument predicts a
      linear speedup with the number of milestones for diffusive processes and an
      exponential speedup for transitions over barriers. The algorithm is also trivial
      to parallelize. As a side result, milestoning also produces the free energy
      profile along the reaction coordinate and is able to describe nonequilibrium
      motions along one (or a few) degrees of freedom.

PMID- 17444754
TI  - Density functional theory fragment descriptors to quantify the reactivity of a
      molecular family: application to amino acids.
AB  - By using the exact density functional theory, one demonstrates that the value of
      the local electronic softness of a molecular fragment is directly related to the
      polarization charge (Coulomb hole) induced by a test electron removed (or added)
      from (at) the fragment. Our finding generalizes to a chemical group a formal
      relation between these molecular descriptors recently obtained for an atom in a
      molecule using an approximate atomistic model [P. Senet and M. Yang, J. Chem.
      Sci. 117, 411 (2005)]. In addition, a practical ab initio computational scheme of
      the Coulomb hole and related local descriptors of reactivity of a molecular
      family having in common a similar fragment is presented. As a blind test, the
      method is applied to the lateral chains of the 20 isolated amino acids. One
      demonstrates that the local softness of the lateral chain is a quantitative
      measure of the similarity of the amino acids. It predicts the separation of amino
      acids in different biochemical groups (aliphatic, basic, acidic, sulfur
      contained, and aromatic). The present approach may find applications in
      quantitative structure activity relationship methodology.

PMID- 17444755
TI  - Theoretical modeling of the kinetics of fibrilar aggregation of bovine beta
      lactoglobulin at pH 2.
AB  - The authors propose a kinetic model for the heat-induced fibrilar aggregation of
      bovine beta-lactoglobulin at pH 2.0. The model involves a nucleation step and a
      simple addition reaction for the growth of the fibrils, as well as a side
      reaction leading to the irreversible denaturation and inactivation of a part of
      the protein molecules. For the early stages of the aggregation reaction, the
      authors obtain an analytical solution of the model. In agreement with their
      experimental results, the model predicts a critical protein concentration below
      where almost no fibrils are formed. The model agrees well with their experimental
      data from in situ light scattering. By fitting the experimental data with the
      model, the authors obtain the ionic strength dependent kinetic rate constants for
      beta-lactoglobulin fibrilar aggregation and the size of the critical nucleus.

PMID- 17444756
TI  - Spike-timing-dependent plasticity in balanced random networks.
AB  - The balanced random network model attracts considerable interest because it
      explains the irregular spiking activity at low rates and large membrane potential
      fluctuations exhibited by cortical neurons in vivo. In this article, we
      investigate to what extent this model is also compatible with the experimentally
      observed phenomenon of spike-timing-dependent plasticity (STDP). Confronted with
      the plethora of theoretical models for STDP available, we reexamine the
      experimental data. On this basis, we propose a novel STDP update rule, with a
      multiplicative dependence on the synaptic weight for depression, and a power law
      dependence for potentiation. We show that this rule, when implemented in large,
      balanced networks of realistic connectivity and sparseness, is compatible with
      the asynchronous irregular activity regime. The resultant equilibrium weight
      distribution is unimodal with fluctuating individual weight trajectories and does
      not exhibit development of structure. We investigate the robustness of our
      results with respect to the relative strength of depression. We introduce
      synchronous stimulation to a group of neurons and demonstrate that the decoupling
      of this group from the rest of the network is so severe that it cannot
      effectively control the spiking of other neurons, even those with the highest
      convergence from this group.

PMID- 17444757
TI  - Reinforcement learning through modulation of spike-timing-dependent synaptic
      plasticity.
AB  - The persistent modification of synaptic efficacy as a function of the relative
      timing of pre- and postsynaptic spikes is a phenomenon known as spike-timing
      dependent plasticity (STDP). Here we show that the modulation of STDP by a global
      reward signal leads to reinforcement learning. We first derive analytically
      learning rules involving reward-modulated spike-timing-dependent synaptic and
      intrinsic plasticity, by applying a reinforcement learning algorithm to the
      stochastic spike response model of spiking neurons. These rules have several
      features common to plasticity mechanisms experimentally found in the brain. We
      then demonstrate in simulations of networks of integrate-and-fire neurons the
      efficacy of two simple learning rules involving modulated STDP. One rule is a
      direct extension of the standard STDP model (modulated STDP), and the other one
      involves an eligibility trace stored at each synapse that keeps a decaying memory
      of the relationships between the recent pairs of pre- and postsynaptic spike
      pairs (modulated STDP with eligibility trace). This latter rule permits learning
      even if the reward signal is delayed. The proposed rules are able to solve the
      XOR problem with both rate coded and temporally coded input and to learn a target
      output firing-rate pattern. These learning rules are biologically plausible, may
      be used for training generic artificial spiking neural networks, regardless of
      the neural model used, and suggest the experimental investigation in animals of
      the existence of reward-modulated STDP.

PMID- 17444758
TI  - A method for selecting the bin size of a time histogram.
AB  - The time histogram method is the most basic tool for capturing a time dependent
      rate of neuronal spikes. Generally in the neurophysiological literature, the bin
      size that critically determines the goodness of the fit of the time histogram to
      the underlying spike rate has been subjectively selected by individual
      researchers. Here, we propose a method for objectively selecting the bin size
      from the spike count statistics alone, so that the resulting bar or line graph
      time histogram best represents the unknown underlying spike rate. For a small
      number of spike sequences generated from a modestly fluctuating rate, the optimal
      bin size may diverge, indicating that any time histogram is likely to capture a
      spurious rate. Given a paucity of data, the method presented here can
      nevertheless suggest how many experimental trials should be added in order to
      obtain a meaningful time-dependent histogram with the required accuracy.

PMID- 17444759
TI  - Penalized probabilistic clustering.
AB  - While clustering is usually an unsupervised operation, there are circumstances in
      which we believe (with varying degrees of certainty) that items A and B should be
      assigned to the same cluster, while items A and C should not. We would like such
      pairwise relations to influence cluster assignments of out-of-sample data in a
      manner consistent with the prior knowledge expressed in the training set. Our
      starting point is probabilistic clustering based on gaussian mixture models (GMM)
      of the data distribution. We express clustering preferences in a prior
      distribution over assignments of data points to clusters. This prior penalizes
      cluster assignments according to the degree with which they violate the
      preferences. The model parameters are fit with the expectation-maximization (EM)
      algorithm. Our model provides a flexible framework that encompasses several other
      semisupervised clustering models as its special cases. Experiments on artificial
      and real-world problems show that our model can consistently improve clustering
      results when pairwise relations are incorporated. The experiments also
      demonstrate the superiority of our model to other semisupervised clustering
      methods on handling noisy pairwise relations.

PMID- 17444760
TI  - Robustness of connectionist swimming controllers against random variation in
      neural connections.
AB  - The ability to achieve high swimming speed and efficiency is very important to
      both the real lamprey and its robotic implementation. In previous studies, we
      used evolutionary algorithms to evolve biologically plausible connectionist
      swimming controllers for a simulated lamprey. This letter investigates the
      robustness and optimality of the best-evolved controllers as well as the
      biological controller hand-crafted by Ekeberg. Comparing cases of random
      variation in intrasegmental or intersegmental weights against each controller
      allows estimates of robustness to be made. We conduct experiments on the
      controllers' robustness at the excitation level, which corresponds to either the
      maximum swimming speed or efficiency by randomly varying the segmental connection
      weights and on some occasions also the intersegmental couplings, through varying
      noise ranges. Interestingly, although the swimming performance (in terms of
      maximum speed and efficiency) of the Ekeberg biological controller is not as good
      as that of the artificially evolved controllers, it is relatively robust against
      noise in the neural networks. This suggests that the natural evolutions have
      evolved a swimming controller that is good enough to survive in the real world.
      Our findings could inspire neurobiologists to conduct real physiological
      experiments to gain a better understanding on how neural connectivity affects
      behavior. The results can also be applied to control an artificial lamprey in
      simulation and possibly also a robotic one.

PMID- 17444761
TI  - A measurement fusion method for nonlinear system identification using a
      cooperative learning algorithm.
AB  - Identification of a general nonlinear noisy system viewed as an estimation of a
      predictor function is studied in this article. A measurement fusion method for
      the predictor function estimate is proposed. In the proposed scheme, observed
      data are first fused by using an optimal fusion technique, and then the optimal
      fused data are incorporated in a nonlinear function estimator based on a robust
      least squares support vector machine (LS-SVM). A cooperative learning algorithm
      is proposed to implement the proposed measurement fusion method. Compared with
      related identification methods, the proposed method can minimize both the
      approximation error and the noise error. The performance analysis shows that the
      proposed optimal measurement fusion function estimate has a smaller mean square
      error than the LS-SVM function estimate. Moreover, the proposed cooperative
      learning algorithm can converge globally to the optimal measurement fusion
      function estimate. Finally, the proposed measurement fusion method is applied to
      ARMA signal and spatial temporal signal modeling. Experimental results show that
      the proposed measurement fusion method can provide a more accurate model.

PMID- 17444762
TI  - Efficient computation and model selection for the support vector regression.
AB  - In this letter, we derive an algorithm that computes the entire solution path of
      the support vector regression (SVR). We also propose an unbiased estimate for the
      degrees of freedom of the SVR model, which allows convenient selection of the
      regularization parameter.

PMID- 17444763
TI  - A novel generic hebbian ordering-based fuzzy rule base reduction approach to
      mamdani neuro-fuzzy system.
AB  - There are two important issues in neuro-fuzzy modeling: (1) interpretability--the
      ability to describe the behavior of the system in an interpretable way--and (2)
      accuracy--the ability to approximate the outcome of the system accurately. As
      these two objectives usually exert contradictory requirements on the neuro-fuzzy
      model, certain compromise has to be undertaken. This letter proposes a novel rule
      reduction algorithm, namely, Hebb rule reduction, and an iterative tuning process
      to balance interpretability and accuracy. The Hebb rule reduction algorithm uses
      Hebbian ordering, which represents the degree of coverage of the samples by the
      rule, as an importance measure of each rule to merge the membership functions and
      hence reduces the number of the rules. Similar membership functions (MFs) are
      merged by a specified similarity measure in an order of Hebbian importance, and
      the resultant equivalent rules are deleted from the rule base. The rule with a
      higher Hebbian importance will be retained among a set of rules. The MFs are
      tuned through the least mean square (LMS) algorithm to reduce the modeling error.
      The tuning of the MFs and the reduction of the rules proceed iteratively to
      achieve a balance between interpretability and accuracy. Three published data
      sets by Nakanishi (Nakanishi, Turksen, & Sugeno, 1993), the Pat synthetic data
      set (Pal, Mitra, & Mitra, 2003), and the traffic flow density prediction data set
      are used as benchmarks to demonstrate the effectiveness of the proposed method.
      Good interpretability, as well as high modeling accuracy, are derivable
      simultaneously and are suitably benchmarked against other well-established neuro
      fuzzy models.

PMID- 17444766
TI  - Validation of surgical simulators.
AB  - Although apprenticeship served surgeons in training well a hundred years ago, the
      complexity of surgical technology in the 21st Century has exponentially increased
      the demands on surgical education. Pelvic trainers can provide the necessary
      basic training for endoscopic and laparoscopic surgeons, but it usually is
      necessary to incorporate live-animal or cadaver practice or both to train fully
      in today's complex procedures. Advances in computer and materials technology have
      allowed the development of realistic simulators, but validation studies are
      required. Reliability is the reproducibility and precision of the test or testing
      device. Validity measures whether the simulator actually is teaching or
      evaluating what it is intended to teach or measure. Face validity relates to the
      realism of the simulator; content validity is a judgment of the appropriateness
      of the simulator as a teaching modality. Criterion validity compares the
      evaluation results from the new simulator with those of the old technique. The
      two types of criterion validity are concurrent - the extent to which the
      simulator correlates with the "gold standard" - and predictive - the extent to
      which the simulator predicts future performance. Construct validity indicates
      whether the simulator is able to distinguish the experienced from the
      inexperienced surgeon. For competency assessment, performance on a simulator
      should predict, or at least correlate with, an individual's performance in the
      operating room. A variety of endourologic models and simulators have been
      described, but only a few have been subjected to validity testing. An even
      greater number of simulators has been developed for laparoscopic skills training,
      but none is dedicated to training for laparoscopic urology. Surgical simulation
      must be used within an effective learning environment, underpinned by knowledge
      and professional attitudes.

PMID- 17444767
TI  - Low-fidelity ureteroscopy models.
AB  - For several reasons, there has been pressure to seek alternatives to the
      Halstedian method of surgical training, both for residents and for practicing
      surgeons faced with a new procedure. The use of bench models to train urology
      residents in order to maximize their operating-room experience is becoming
      popular. Realistic latex models and virtual-reality simulators have been
      introduced. However, the model does not have to look realistic as long as the
      trainee can practice the pertinent steps of the procedure using the same skills:
      training on a well-designed low-fidelity model confers the same benefit as
      training on a high-fidelity model. Bench model training in ureteroscopy appears
      to have a durable effect on the clinical performance of surgical residents. More
      research is necessary to validate training on bench models and may lead to more
      objective measures of surgical competency.

PMID- 17444768
TI  - Mechanical simulators for training for laparoscopic surgery in urology.
AB  - BACKGROUND AND PURPOSE: The introduction of laparoscopic surgery into urology has
      led to new training concepts differing significantly from previous concepts of
      training for open surgery. This paper focuses on the type and importance of
      mechanical simulators in laparoscopic training. MATERIALS AND METHODS: On the
      basis of our own studies and experience with the development of various concepts
      of laparoscopic training, including different modules (i.e., Pelvi-trainer,
      animal models, clinical mentoring) since 1991, we reviewed the current literature
      concerning all types of simulators. We focused on training for laparoscopic
      ablative and reconstructive surgery using mechanical simulators. RESULTS: The
      principle of a mechanical simulator (i.e., a box with the possibility of trocar
      insertion) has not changed during the last decade. However, the types of Pelvi
      trainers and the models used inside have been improved significantly. According
      to the task of the simulator, various sophisticated models have been developed,
      including standardized phantoms, animal organs, and even perfused segments of
      porcine organs. For laparoscopic suturing, various step-by-step training concepts
      have been presented. These can be used for determination of the ability of a
      physician with an interest in laparoscopic surgery, but also to classify the
      training status of a laparosopic surgeon. CONCLUSIONS: Training in laparoscopic
      surgery has become an important topic, not only in learning a procedure, but also
      in maintaining skills and preparing for the management of complications. For
      these purposes, mechanical simulators will definitely play an important role in
      the future.

PMID- 17444769
TI  - Ureteroscopy and cystoscopy simulation in urology.
AB  - Transformations of many aspects of surgery have provided a potentially fertile
      ground for the implementation of surgical simulators in the medical mainstream.
      The expansion of minimally invasive diagnostic and therapeutic modalities,
      increasing healthcare demands, fiscal constraints, and sensitivity to medicolegal
      considerations limit resident instruction and practical experience in the
      operating room. Furthermore, the need for objective, structured assessments of
      surgical residents during training and the requirement for physicians to gain and
      maintain certification demand that innovative solutions be sought. Surgical
      simulators are poised to deliver broad-based training experiences to trainees of
      all levels. In urology, simulation has been centered on endourologic procedures,
      namely ureteroscopy and cystoscopy. In this paper, various models of simulation
      developed for ureteroscopy and cystoscopy in urology are reviewed, with a brief
      description of each model, its benefits and disadvantages, and current research
      surrounding each simulation model.

PMID- 17444770
TI  - Percutaneous renal access simulators.
AB  - Percutaneous renal access is an integral step in percutaneous renal drainage and
      percutaneous nephrolithotomy. Urologists are increasingly obtaining access
      themselves, as this eliminates reliance on a second "surgeon" and increases
      flexibility with respect to procedure timing and the location of the access
      tract. Surprisingly few models have been developed to train urologists in
      percutaneous renal access. Harvested porcine kidney/ureter units mounted so they
      can be viewed radiographically and accessed by needle puncture through material
      simulating the human flank have been incorporated into two models. The PERC
      Mentor (Simbionix; Lod, Israel) is a virtual-reality simulator developed
      specifically for training in percutaneous renal puncture. Hands-on intraoperative
      training continues to be the primary method for learning percutaneous renal
      access. However, bench model and simulator-based education offer a useful
      adjunct.

PMID- 17444771
TI  - Laparoscopy simulators.
AB  - To reduce the complication rate associated with laparoscopic surgery and to
      improve training, several simulators have been incorporated into training
      curricula and skills courses. We discuss the advantages and disadvantages and
      compare the different types of simulators available. We also reviewed the
      literature to assess the acquisition of skills using these simulators and their
      transfer to real operations. It is important to realize that currently, any form
      of simulation is merely an adjunct to, and not a replacement for, traditional
      methods of training and that supervision and feedback are essential. More
      collaboration is needed between urologists and simulator companies to produce
      operation-specific simulated modules for urologic procedures.

PMID- 17444772
TI  - Review of trainers for transurethral resection of the prostate skills.
AB  - Performance of transurethral resection of the prostate and bladder involves the
      ability to work in a small three-dimensional space while receiving two
      dimensional visual feedback. The operation also demands adept psychomotor
      abilities, as one has to navigate the resectoscope and the loop continuously and
      simultaneously while managing the electrical current with the use of both hands
      and a foot pedal. The fact that the procedure is performed in a fluid environment
      and that the field often is obscured is an important factor to consider when
      creating a teaching tool, as the debris and blood can be disorienting to the
      resectionist in training. Historically, this training problem was addressed with
      sheer case volume, but the number of procedures performed during a residency has
      declined. Limbs and Things (Bristol, UK) created a synthetic "physical"
      disposable model of the prostate that allows the user to practice basic cutting
      skills. No usability or validation studies have been published on this model.
      Several virtual-reality (VR) TURP simulators have been described, with varying
      degrees of preliminary validation studies. The University of Washington VR TURP
      Trainer is licensed to Medical Education Technologies, Inc. (METI, Sarasota, FL).
      A force-feedback device has been integrated. The simulator has an integrated
      curriculum with subtask exercises, such as navigation, cutting, coagulation, and
      full resection modules. It logs motion and force data, as well as operative
      errors, grams of tissue resected, blood loss, irrigant volume, foot pedal use,
      and differential time spent with orientation, cutting, or coagulation. An AHRQ
      funded multi-institutional predictive validity study is in progress, examining
      this simulator's ability to improve residents' performance in the operating room.

PMID- 17444773
TI  - Virtual reality-assisted robotic surgery simulation.
AB  - For more than a decade, advancing computer technologies have allowed
      incorporation of virtual reality (VR) into surgical training. This has become
      especially important in training for laparoscopic procedures, which often are
      complex and leave little room for error. With the advent of robotic surgery and
      the development and prevalence of a commercial surgical system (da Vinci robot;
      Intuitive Surgical, Sunnyvale, CA), a valid VR-assisted robotic surgery simulator
      could minimize the steep learning curve associated with many of these complex
      procedures and thus enable better outcomes. To date, such simulation does not
      exist; however, several agencies and corporations are involved in making this
      dream a reality. We review the history and progress of VR simulation in surgical
      training, its promising applications in robotic-assisted surgery, and the
      remaining challenges to implementation.

PMID- 17444774
TI  - Videotape mentoring and surgical simulation in laparoscopic courses.
AB  - As laparoscopic approaches to core urologic procedures continue to supplant their
      open counterparts, the demand to train urologists who received inadequate
      exposure to these techniques during residency has intensified. The acquisition of
      laparoscopic skills has been aided greatly by the introduction of hand-assisted
      laparoscopic surgery (HALS). In another training method, participants completed
      the standard animate and inanimate course training, then entered a mentoring
      relationship with their instructor, including an observational period and
      performance of several complex laparoscopic operations with the assistance of the
      mentor surgeon. However, the time commitment, compensation issues, and need for
      temporary operating privileges are obstacles to this approach. A number of
      studies have demonstrated that laparoscopic skills can be measured on a
      videotrainer and that ability improves with repetitive performance. Senior
      urologists with minimal initial knowledge may benefit from laparoscopic skills
      training videotape analysis and critique. Laparoscopic simulators can improve,
      not only the psychomotor skills required to perform laparoscopy, but operative
      performance as well. Ultimately, preoperative images and data may be interfaced
      with robotic simulation software to allow practice of virtual operations with
      realistic tissue photo-representation prior to performing them on patients.
      Improvements in laparoscopic surgical simulation and application of these newly
      acquired skills to a simulated patient will ultimately eliminate the learning
      curve on actual patients and provide a useful means of establishing competence.

PMID- 17444775
TI  - Human performance testing and simulators.
AB  - Virtual-reality (VR) simulation offers the opportunity to practice surgical
      techniques and gain experience outside the operating room. Using VR simulators
      and tools recently developed by human performance researchers, different aspects
      of human performance (innate ability) can be measured objectively. These novel
      tools, General Systems Performance Theory, and application of nonlinear causal
      resource analysis (NCRA) may allow us to utilize VR simulators, not only to train
      physicians, but possibly to predict their performance prior to training. By
      analyzing objective measures of basic performance resources (BPRs) with
      performance models developed with NCRA, we showed that BPRs can predict a
      subject's ability to perform high-level tasks. Two pilot studies suggested that
      this approach may objectively identify limitations of the surgeons with the most
      worrisome performance scores. Thus, VR simulation and performance testing may
      help with identification and remediation of residents with poor endoscopic skills
      and with optimization of surgical training protocols. Although the initial
      observations provide encouraging results for objective prediction of surgical
      performance and identification of performance-limiting resources, further
      investigation in larger cohorts of surgical trainees appears warranted.

PMID- 17444776
TI  - Is the holmium:YAG laser the best intracorporeal lithotripter for the ureter? A 3
      year retrospective study.
AB  - PURPOSE: To study the efficiency and safety of holmium:YAG laser lithotripsy for
      ureteral stones. PATIENTS AND METHODS: A series of 188 patients with 208 ureteral
      stones were treated with semirigid ureteroscopy and holmium:YAG laser lithotripsy
      from January 2003 to December 2005. Of the stones, 116 were lower ureteral, 37
      middle ureteral, and 55 upper ureteral. RESULTS: The success rate was 92.7% at
      the time of ureteroscopy and 96.7% at 3 months. The failures were secondary to
      retropulsion of the stones (3.3%). There were no perforations and one stricture.
      Stenting was done in 90% of patients. CONCLUSIONS: The Holmium:YAG laser is an
      ideal intracorporeal lithotripter for ureteral calculi, with a high success rate
      and low morbidity.

PMID- 17444777
TI  - In-vitro gliding resistance of Lapra-Ty clip on polypropylene and glycolide
      sutures.
AB  - BACKGROUND AND PURPOSE: The LapraTy clip (LTc) is a useful tool for supplementing
      knot-tying during reconstructive laparoscopic surgery. However, data regarding
      its safety and efficacy are scarce. We critically assessed the in-vitro
      performance of the LTc over different sizes of two suture materials commonly used
      during reconstructive procedures. MATERIALS AND METHODS: The gliding resistance
      (GR) of one or two LTcs was tested on various sizes of both Polysorb and Prolene
      sutures. The GR of each suture was then compared with its breaking strength.
      Forces were measured using a Vernier Force Sensor. RESULTS: The GR of one LTc was
      significantly lower than the breaking strength of all Polysorb and Prolene suture
      sizes with the exception of 7-0 Prolene, with which the suture broke before the
      LTc slipped off. When two LTcs were placed sequentially, the GR increased
      significantly compared with a single LTc and was equal to or greater than the
      breaking strength for Polysorb 3-0 to 5-0 and Prolene 3-0 to 6-0. The percentage
      of GR over breaking strength was inversely related to suture size and was
      significantly greater with Prolene than with the Polysorb suture of the same
      size. CONCLUSIONS: Our results provide a better understanding of the resistive
      force an LTc offers before slipping and therefore failing. The results observed
      with Prolene sutures are encouraging and must be further investigated in an
      animal study to confirm the safety of the LTc when used during reconstructive
      procedures.

PMID- 17444778
TI  - Impact of collecting-system repair during laparoscopic partial nephrectomy.
AB  - PURPOSE: Laparoscopic partial nephrectomy (LPN) is a complex procedure frequently
      reserved for small, peripherally located renal tumors. Deep, infiltrating lesions
      often necessitate collecting system repair (CSR), mandating further
      intracorporeal suturing and reconstruction. We compared our experience with LPN
      where CSR was and was not required after tumor resection. PATIENTS AND METHODS:
      Between October 2002 and December 2005, 84 patients underwent LPN. Tumor excision
      with pelvicaliceal system injury occurred in 52 patients, whereas 32 patients
      required no CSR. Perioperative and pathologic data were compared in the two
      groups. RESULTS: Tumors with CSR were larger (mean 2.9 cm v 2.1 cm for non-CSR
      procedures; P = 0.001) and had larger pathologic specimen weights (mean 58.2 g v
      21.8 g; P = 0.05). Blood loss (mean 210 mL) and hospital stay (mean 2.7 days)
      were similar in the two groups. Warm ischemia time (WIT) (mean 36.6 v 27.7
      minutes; P < 0.001) and operative time (mean 238 v 207 minutes; P = 0.03) were
      longer in the CSR group. The intraoperative hemorrhage rate (7.7% v 9.4%; P =
      0.34) and rate of conversion to open surgery (7.7% v 9.4%; P = 0.29) were
      similar, as were the incidences of postoperative bleeding (7.7% v 3.1%; P = 0.28)
      and urinary leakage (1.9% v 0; P = 0.62). CONCLUSION: Laparoscopic partial
      nephrectomy involving CSR is a technically demanding procedure that necessitates
      longer WIT and overall surgical time. However, when performed by an experienced
      laparoscopic surgeon, comparable complication rates and blood loss are observed.
      Technical variations for hemostasis, such as argon-beam coagulation and FloSeal
      and the use of the LapraTy clip for pelvicaliceal and parenchymal suture repair
      may facilitate LPN for more deeply invasive tumors.

PMID- 17444779
TI  - Laparoscopic cryotherapy for pediatric angiomyolipoma: the first report.
AB  - BACKGROUND AND PURPOSE: Renal cryotherapy for pediatric angiomyolipoma has never
      been reported in the literature. We present the first experience with this
      procedure, describing techniques and short-term outcome. CASE REPORT: A 14-year
      old girl was being followed for a 2-cm left renal angiomyolipoma. Growth was
      demonstrated by ultrasonography and CT imaging over a 2-year period, and the
      family desired intervention. A transperitoneal approach employing three 5-mm
      laparoscopic ports was used. Tumor size was measured by intraoperative
      ultrasonography as 25 x 28 mm. Intraoperative biopsy was done with a biopsy gun
      through the lateral port. An 8-mm cryoprobe was utilized. Two freeze-thaw cycles
      were performed with cooling to -160 degrees C. Hemostasis was accomplished with
      thrombin (FloSeal) and oxidized cellulose (Surgicel). RESULTS: The operative time
      was 92 minutes, and the blood loss was minimal. No perioperative complications
      occurred. There was mild perioperative hematuria that resolved within 20 hours
      without stenting. The hospital stay was 46 hours. There were no complications or
      hematuria at 1-week postoperative follow-up. CONCLUSION: Laparoscopic cryotherapy
      can be performed in the pediatric population. To our knowledge, this is the first
      case of pediatric renal angiomyolipoma managed with laparoscopic cryotherapy.

PMID- 17444780
TI  - Open versus laparoscopy-assisted radical cystectomy: results of a prospective
      study.
AB  - BACKGROUND AND PURPOSE: Laparoscopic radical cystectomy is confined to centers
      where advanced laparoscopy is performed, and its role is not yet well clear. Our
      aim was to evaluate, through a prospective comparative study, the advantages of
      the laparoscopic compared with an open approach. PATIENTS AND METHODS: From
      November 2002 to December 2005, all the patients in our center who were found to
      have muscle-invasive bladder cancer without clinical evidence of lymph-node
      involvement and an American Society of Anesthesiologists (ASA) score <4 were
      included in a prospective nonrandomized study. Group A (N = 22) underwent open
      radical cystectomy, whereas group B (N = 20) underwent laparoscopy-assisted
      radical cystectomy. The two groups were demographically comparable. We evaluated
      the mean age, clinical stage, ASA score, operative time, blood loss,
      intraoperative complications and transfusions, type of diversion, time of
      catheterization, analgesic consumption, start of oral nutrition, rate of
      postoperative complications, length of hospital stay, pathologic diagnosis of the
      specimen, number of lymph nodes removed, and the oncologic outcome. RESULTS: No
      significant statistical difference was observed between the two groups in
      intraoperative and postoperative parameters except for analgesic consumption and
      the start of oral nutrition (P < 0.05). The mean operative time was 260 minutes
      (range 210-290 minutes) for group A and 284 minutes (range 260-305 minutes) for
      group B. The mean blood loss was 770 mL (range 450-870 mL) in group A and 520 mL
      (range 400-620 mL) in group B. The rate of autologous transfusion was 18% in
      group A and 10% in group B. Seventeen ileal diversions and five neobladder
      creations were performed in group A, whereas the Bricker diversion was used in 10
      cases in group B, and a neobladder was chosen in the 10 other cases. CONCLUSION:
      Laparoscopy-assisted radical cystectomy is a safe procedure, like open surgery,
      but it offers the advantage of minimal invasiveness, represented by reduced
      analgesic consumption and early recovery of peristalsis with rapid oral
      nutrition.

PMID- 17444781
TI  - Renal-artery pseudoaneurysm after laparoscopic partial nephrectomy.
AB  - BACKGROUND AND PURPOSE: Laparoscopic partial nephrectomy (LPN) has emerged as a
      minimally invasive treatment for small renal masses. The most common
      complications include hemorrhage and urinary-fistula formulation. Renal-artery
      pseudoaneurysm has been described after open nephron-sparing surgery. We present
      two cases of renal-artery aneurysm following LPN. CASE REPORTS: Two patients with
      incidentally discovered renal masses underwent LPN with excellent hemostasis and
      presented in a delayed fashion with gross hematuria and flank pain. Both patients
      were treated with angiographic coil embolization, resulting in resolution of the
      pseudoaneurysms on postprocedure imaging. CONCLUSIONS: Renal-artery
      pseudoaneurysm is a potentially life-threatening complication of LPN. Patients
      present in a delayed fashion with gross hematuria, flank pain, or both. The
      treatment of choice is angiography with selective coil embolization.

PMID- 17444782
TI  - Percutaneous treatment of calculi in reconstructed bladder.
AB  - PURPOSE: To report our results with percutaneous removal of calculi from
      reconstructed bladders. PATIENTS AND METHODS: Twelve patients with reconstructed
      bladders who underwent endoscopic cystolithotomy were identified from our
      departmental database, and retrospective review of case notes and imaging was
      performed. RESULTS: Access was gained via an ultrasound-guided new tract in 9
      patients (75%). An old suprapubic tract site was used in two patients, and the
      Mitrofanoff stoma was the route of access in one patient. The procedure was
      successful, with stone clearance achieved in all 12 cases. No major complications
      were observed. At a median follow up of 24 months, stone recurrence was observed
      in 5 patients (42%), 4 of whom underwent repeat procedures. Follow-up showed no
      change in continence in the patient with a Mitroffanoff stoma. CONCLUSION:
      Percutaneous cystolithotomy is a safe and effective minimally invasive option for
      removal of stones in a reconstructed bladder. We recommend endoscopic removal as
      the treatment of choice in these patients.

PMID- 17444783
TI  - Basket design as a factor in retention and release of calculi in vitro.
AB  - PURPOSE: To compare stone retrieval and release from seven basket designs in
      vitro. MATERIALS AND METHODS: We tested two tipped and one tipless NCompass
      models, three other tipless Nitinol designs (NCircle, Sur-Catch, and Dimension),
      and the Segura Hemisphere for their ability to retrieve and release single beads
      8, 6, 5.6, and 5 mm diameter and multiple beads 3.6 mm diameter in both a
      ureteral and a caliceal model in three separate attempts. RESULTS: In the
      ureteral model, all baskets were successful in retrieving all sizes of single
      beads. With multiple 3.6-mm beads, only the NCompass and Dimension designs were
      able to retrieve at least two of three beads in all attempts. With the exception
      of the Segura Hemisphere, all designs were successful in releasing all bead
      sizes. In the caliceal model, only the NCircle, Dimension, and tipless NCompass
      models were able to retrieve all bead sizes in 100% of the trials. The tipped
      NCompass and Hemisphere designs were unable to retrieve any beads in this model.
      The Sur-Catch basket was successful in the retrieval of large beads only. The
      Dimension articulating design was the only basket able to release all bead sizes
      in all attempts. The tipless NCompass basket did not release any of the beads
      once engaged. CONCLUSION: Nitinol basket designs show excellent retrieval and
      release capabilities in the in-vitro ureteral model. The articulating Nitinol
      basket has the best stone-releasing capability of all baskets tested.

PMID- 17444784
TI  - In-Vivo relation between CT attenuation value and shockwave fragmentation.
AB  - PURPOSE: To use CT attenuation numbers as a means of determining the
      susceptibility of an artificial stone to in-vivo fragmentation with
      extracorporeal shockwave lithotripsy (SWL). MATERIALS AND METHODS: Four types of
      artificial kidney stones having different CT attenuation values were used. One
      randomly selected stone was implanted in the renal pelvis of a kidney of 12 young
      pigs and exposed in vivo to 2500 shockwaves (21 kV) using an electrohydraulic
      lithotripter. Bilateral nephrectomy was performed after SWL. Fragments were
      strained through a mesh with a 3.1-mm grid, and the debris left on the mesh was
      dried and weighed. Fragmentation coefficients (FCs) were associated with CT
      attenuation values using a statistical model. RESULTS: The relation between FC
      and CT number was significant, indicating that as CT attenuation increases, FC is
      reduced. Larger stone fragments were obtained from stones with higher CT numbers.
      Initial stone weight was not a significant explanation for variations in FC.
      CONCLUSION: The CT values could be helpful in selecting patients for SWL in the
      future. However, other parameters such as stone porosity, shape, and roughness
      also will have to be considered.

PMID- 17444785
TI  - Analysis of surgical smoke produced by various energy-based instruments and
      effect on laparoscopic visibility.
AB  - PURPOSE: We analyzed the smoke plume produced by various energy-based
      laparoscopic instruments and determined its effect on laparoscopic visibility.
      MATERIALS AND METHODS: The Bipolar Macroforceps, Harmonic Scalpel, Floating Ball,
      and Monopolar Shears were applied in vitro to porcine psoas muscle. An
      Aerodynamic Particle Sizer and Electrostatic Classifier provided a size
      distribution of the plume for particles >500 nm and <500 nm, and a geometric mean
      particle size was calculated. A Condensation Particle Counter provided the total
      particle-number concentration. Electron microscopy was used to characterize
      particle size and shape further. Visibility was calculated using the measured
      size distribution data and the Rayleigh and Mie light-scattering theories.
      RESULTS: The real-time instruments were successful in measuring aerosolized
      particle size distributions in two size ranges. Electron microscopy revealed
      smaller, homogeneous, spherical particles and larger, irregular particles
      consistent with cellular components. The aerosol produced by the Bipolar
      Macroforceps obscured visibility the least (relative visibility 0.887) among the
      instruments tested. Particles from the Harmonic Scalpel resulted in a relative
      visibility of 0.801. Monopolar-based instruments produced plumes responsible for
      the poorest relative visibility (Floating Ball 0.252; Monopolar Shears 0.026).
      CONCLUSIONS: Surgical smoke is composed of two distinct particle populations
      caused by the nucleation of vapors as they cool (the small particles) and the
      entrainment of tissue secondary to mechanical aspects (the large particles). High
      concentrations of small particles are most responsible for the deterioration in
      laparoscopic vision. Bipolar and ultrasonic instruments generate a surgical plume
      that causes the least deterioration of visibility among the instruments tested.

PMID- 17444790
TI  - The boomers are coming: a total cost of care model of the impact of population
      aging on the cost of chronic conditions in the United States.
AB  - The purpose of this study is to estimate the impact of population aging on
      medical costs over the next five decades in the United States. Specifically, we
      focus on the impact of aging on the chronic and/or expensive conditions most
      often included in disease management programs: coronary artery disease (CAD),
      congestive heart failure (CHF), diabetes, asthma, pregnancy, psychiatry, and
      chemical dependency. We apply estimated age-, gender-, and condition-specific
      annualized costs to the projected US population in each age and gender group for
      future years, through 2050, to provide an estimate of future healthcare costs.
      The primary data sources are pooled claims and membership for 2002 and 2003 for
      HealthPartners, a large midwestern health plan. Secondary sources are US
      annualized medical costs for 2003 and US Census Bureau demographic projections
      for the next five decades. Using the Episodes Treatment Group (ETG) grouper from
      Symmetry, we grouped HealthPartners data into 574 clinically meaningful episodes
      of care units. We then aggregate selected ETGs into the conditions reported in
      this study. Using data for all types of health services, we find that aging will
      have a greater impact on per capita costs for diseases where the ratio of costs
      for older versus younger ages is greater, such as CHF, CAD, and diabetes. In
      addition, we project that aging of the US population will actually reduce per
      capita costs for pregnancy and infertility, chemical dependency, and psychiatric
      conditions. Aging will have more of an impact on care for specific chronic
      diseases. These projections can inform health policy and planning as providers of
      health care, health plans, disease management vendors, and the government
      anticipate meeting future US healthcare needs.

PMID- 17444791
TI  - Convenient care clinics: the future of accessible health care.
AB  - The need for accessible, affordable, quality health care in the United States has
      never been greater. In response to this need, convenient care clinics (CCCs) are
      being launched across the country to help provide care to meet the basic health
      needs of the public. In CCCs, highly qualified health care providers diagnose and
      treat common health problems, triage patients to the appropriate level of care,
      advocate for a medical home for all patients, and reduce unnecessary visits to
      emergency rooms and Urgent Care Clinics. CCCs have been called a "disruptive
      innovation" because they are consumer driven. They serve as a response to many
      patients who are unhappy with the current conventional health care delivery
      system--a system that is challenged to provide access to basic health care
      services when people need it the most. CCCs are based in retail stores and
      pharmacies. They are primarily staffed by nurse practitioners (NPs). Some CCCs
      are staffed by physician assistants (PAs) and physicians. The authors acknowledge
      the important roles of both PAs and physicians in CCCs; however, this paper
      primarily provides education about the role of NPs in CCCs. CCCs have evolved at
      a time when our health care system is floundering, and the need for accessible,
      affordable health care is at its greatest. The CCC model provides an accessible,
      affordable entry point into the health care system for those who previously were
      restricted access.

PMID- 17444792
TI  - Current trends in pharmacy benefit designs: a threat to disease management in
      chronic complex diseases.
AB  - With a focus on those patients who are candidates for treatment with biologic
      agents, we review the impact that current pharmacy benefit trends have on
      patients with chronic complex diseases and how they affect opportunities for
      disease management in this unique patient population. Dramatic increases in
      health care costs have led to a variety of strategies to manage cost. Many of
      these strategies either limit access to care or increase the patient's
      responsibility for choosing and paying for care, especially for medications.
      These strategies have a disproportionate impact on patients with chronic complex
      diseases, particularly those who require the use of biologic medications. A
      fundamental prerequisite of disease management has been coverage of disease
      modifying therapies. If current pharmacy benefit trends continue, unintended
      consequences will likely occur including lost opportunities for disease
      management. Current pharmacy benefit trends could adversely impact disease
      management, particularly for patients requiring the use of biologic agents.
      Health plans should consider innovative benefit designs that reflect an
      appropriate level of cost sharing across all key stake-holders, ensuring
      appropriate access to needed therapies. Additional research is needed to clarify
      the value of newer approaches to therapies or benefit design changes.

PMID- 17444793
TI  - Impact of different levels of weight loss on blood pressure in overweight and
      obese women.
AB  - This study sought to determine the impact of different levels of weight loss on
      blood pressure in overweight/obese women. One hundred fifty-nine overweight/obese
      women (age 48.7 +/- 9.7, weight 101.3 +/- 18.7 kg, BMI 37.3 +/- 6.6 kg/m(2))
      completed a six-month clinical weight loss program that included weekly
      nutrition, behavior, and exercise instruction. Participants consumed a very-low
      energy diet (VLED) for 12 weeks. VLED was followed by four weeks of gradual
      reintroduction to solid foods. At week 16, participants received a diet to
      maintain weight or slightly reduce weight (<0.5 lb/week) which they followed for
      the duration of the study. All lab and blood pressure assessments were performed
      at baseline and six months. Three groups were formed according to the proportion
      of weight loss after six months; Group 1 had < 10% (n = 19), Group 2 had 10%-20%
      (n = 64), and Group 3 had >20% (n = 76) weight loss. Differences in systolic
      blood pressure (mm Hg) were found in dose response fashion for weight loss at six
      months with 125 +/- 17 (<10%), 119 +/- 13 (10%-20%), and 117 +/- 15 (>20%; p =
      0.005). Differences in diastolic blood pressure (mm Hg) were also found in dose
      response fashion with 81 +/- 9 (<10%), 77 +/- 9 (10%-20%), and 75 +/- 9 (20%; p =
      0.003). These data indicate that increasing weight loss beyond 10% of initial
      body weight may provide added improvements in blood pressure compared to less
      than 10% weight loss in overweight or obese women.

PMID- 17444794
TI  - Effect of disease management on prescription drug treatment: what is the right
      quality measure?
AB  - Measures of medication adherence have become common parameters with which disease
      management (DM) programs are being evaluated, leading to the question of how this
      concept should be measured in the particular context of a DM intervention. We
      hypothesize that DM improves adherence to prescriptions more than the rate with
      which prescriptions are being filled. We used health plan claims data to
      construct 13 common measures of medication adherence for five chronic conditions.
      The measures were operationalized in three different ways: the Prescription Fill
      Rate (PFR), which requires only one prescription; the Medication Possession Ratio
      (MPR), which requires a supply that covers at least 80% of the year; and the
      Length of Gap (LOG), which requires no gap greater than 30 days between
      prescriptions. We compared results from a baseline year to results during the
      first year of a DM program. Changes in adherence were quite small in the first
      year of the intervention, with no changes greater than six percentage points. In
      the intervention year, three measures showed a significant increase based on all
      three operational definitions, but two measures paradoxically decreased based on
      the PFR. For both, the MPR and the LOG suggested either no change or significant
      improvement. None of the MPR and LOG measures pointed toward significantly lower
      compliance in the intervention year. Different ways to operationalize the concept
      of medication adherence can lead to fundamentally different conclusions. While
      more complex, MPR- and LOG-based measures could be more appropriate for DM
      evaluation. Our initial results, however, need to be confirmed by data covering
      longer term follow-up.

PMID- 17444795
TI  - Association between frequency of telephonic contact and clinical testing for a
      large, geographically diverse diabetes disease management population.
AB  - Diabetes disease management (DM) programs strive to promote healthy behaviors,
      including obtaining hemoglobin A1c (A1c) and low-density lipoprotein (LDL) tests
      as part of standards of care. The purpose of this study was to examine the
      relationship between frequency of telephonic contact and A1c and LDL testing
      rates. A total of 245,668 members continuously enrolled in diabetes DM programs
      were evaluated for performance of an A1c or LDL test during their first 12 months
      in the programs. The association between the number of calls a member received
      and clinical testing rates was examined. Members who received four calls
      demonstrated a 24.1% and 21.5% relative increase in A1c and LDL testing rates,
      respectively, compared to members who received DM mailings alone. Response to the
      telephonic intervention as part of the diabetes DM programs was influenced by
      member characteristics including gender, age, and disease burden. For example,
      females who received four calls achieved a 27.7% and 23.6% increase in A1c and
      LDL testing, respectively, compared to females who received mailings alone; by
      comparison, males who were called achieved 21.2% and 19.9% relative increase in
      A1c and LDL testing, respectively, compared to those who received mailings alone.
      This study demonstrates a positive association between frequency of telephonic
      contact and increased performance of an A1c or LDL test in a large, diverse
      diabetes population participating in DM programs. The impact of member
      characteristics on the responsiveness to these programs provides DM program
      designers with knowledge for developing strategies to promote healthy behaviors
      and improve diabetes outcomes.

PMID- 17444796
TI  - Topically applied naltrexone restores corneal reepithelialization in diabetic
      rats.
AB  - PURPOSE: Complications of diabetes include an increased risk of delayed corneal
      epithelial wound healing. This study examined the efficacy of naltrexone (NTX),
      an opioid antagonist, by topical application in facilitating the repair of such
      lesions. METHODS: NTX, in concentrations of 10(-4), 10(-5), or 10(-6) M, was
      administered topically 4 times per day for 7 days to the abraded eye of type 1
      diabetic rats (DB), DB animals receiving insulin and normoglycemic (DB-IN), and
      nondiabetic (Normal) rats, beginning 8 weeks following the onset of diabetes.
      RESULTS: In comparison to DB animals receiving sterile vehicle (SV), DB-NTX rats
      had 25%-83% smaller defects, a reduction of 24 h (approximately 33%) in closure
      time, and 20%-42% faster healing rates. DB rats receiving 10(-4) and 10(-5) M NTX
      were equal to, or surpassed, Normal animals in all parameters of wound closure.
      NTX also enhanced wound repair in DB-IN and Normal animals relative to their
      respective SV group. No adverse effects of NTX administration on a variety of
      noninvasive or invasive measures were discerned. CONCLUSIONS: Topically applied
      NTX is not only feasible, but also effective over a one hundredfold dosage for
      accelerating corneal wound healing in diabetic subjects.

PMID- 17444797
TI  - Resistance to blood flow in the rabbit ophthalmic artery after topical treatment
      with timolol.
AB  - PURPOSE: The aim of this study was to investigate the resistance to blood flow in
      the ophthalmic artery of rabbits receiving topical treatment with timolol.
      METHODS: Eight (8) New Zealand albino rabbits received 20 mul of timolol
      treatment (vehicle, 0.1%, 0.33%, 1%, and 3.3%) on the right eye. Blood-flow
      velocity in the ophthalmic artery was determined in the treated eye using color
      Doppler imaging (CDI) with a 12-MHz linear ultrasound transducer prior to the
      treatment and at 0.5, 1, 1.5, 2, and 3 h after the treatment. Intraocular
      pressure (IOP) was measured in both eyes, using a pneumatonometer at the same
      time points. Pourcelot's resistive index of blood flow was calculated, using the
      peak systolic velocity and the end diastolic velocity. A control experiment was
      performed with CDI obtained from the right eye when the left eye was treated with
      1% timolol. RESULTS: In the eye treated with 1% and 3.3% timolol, a dose
      dependent increase in the resistive index of blood flow occurred in the
      ophthalmic artery. No change in the resistive index occurred when the
      contralateral eye was treated with 1% timolol. Changes of IOP were not different
      between the two eyes under all the experimental conditions. Timolol, at all
      concentrations, caused a significant reduction of heart rate. A similar reduction
      of heart rate occurred when either eye was treated with 1% timolol. CONCLUSIONS:
      Topical treatment with timolol in rabbits can increase the resistance to blood
      flow in the ophthalmic artery. This effect is caused by a mechanism local to the
      eye and is not dependent on an IOP change.

PMID- 17444798
TI  - Sympathetic activities influence blood-flow velocity and resistance in the rabbit
      ophthalmic artery.
AB  - PURPOSE: The aim of this study was to investigate sympathetic influences on blood
      flow velocity and resistance in the rabbit ophthalmic artery during the
      transition period from the light to the dark phase. METHODS: Eight (8) New
      Zealand albino rabbits were entrained to a daily 12-h light and 12-h dark cycle.
      Blood-flow velocities in the ophthalmic artery were determined at -2 (baseline),
      0, 2, and 4 h after the onset of darkness. Pulsed and color Doppler images of the
      ophthalmic artery were recorded using a 12-MHz linear ultrasound transducer.
      Resistive index of blood flow was calculated using the peak systolic velocity and
      the end diastolic velocity. Measurements of intraocular pressure (IOP) were
      taken, using a pneumatonometer at the same time points. Blood-flow velocity,
      resistive index, and IOP were also determined in the same rabbits after surgical
      decentralization of the ocular sympathetic nerves. RESULTS: Compared with the
      baseline at -2 h, a significant increase in the resistive index of blood flow in
      the ophthalmic artery occurred at 2 and 4 h after the onset of darkness. Parallel
      elevations of IOP were observed. After the sympathetic decentralization, peak
      systolic and end diastolic velocities decreased and resistive indexes increased
      from the presurgical values in the ophthalmic artery. In the postsurgical
      rabbits, elevation of IOP was absent during the light-dark transition period.
      There was also no time-dependent increase of resistive index in the ophthalmic
      artery. CONCLUSIONS: During the light-dark transition period, resistance to blood
      flow in the rabbit ophthalmic artery increases in parallel to IOP elevation. The
      removal of sympathetic activities decreases blood-flow velocity, but increases
      blood-flow resistance. Like the endogenous elevation of IOP, the time-dependent
      increase of resistance to blood flow in the rabbit ophthalmic artery during the
      light-dark transition period depends upon, at least partially, ocular sympathetic
      activities.

PMID- 17444799
TI  - Topical aldose reductase inhibitor formulations for effective lens drug delivery
      in a rat model for sugar cataracts.
AB  - PURPOSE: In the topical delivery of drugs to the lens, drug retention on the eye
      surface is considered to be important because increased retention on the ocular
      surface should lead to increased ocular absorption of a drug through the cornea
      into the aqueous humor and subsequently the lens. The aim of this study was to
      investigate whether increasing the viscosity of a topical aldose reductase
      inhibitor suspension increases the lenticular bioavailability of the inhibitor
      and whether such a formulation can arrest sugar cataract formation. METHODS: Five
      topical suspensions of 3% 2-methylsorbinil (2-MS) were prepared using (1)
      hydroxypropyl methylcellulose (HPMC, 0.5% w/v), (2) xanthan gum (0.5% w/v), (3)
      gellan gum (0.5% w/v), (4) carbopol (0.25% w/v), and (5) carbopol (0.25% w/v)-
      hydroxypropyl methylcellulose (HPMC) (0.25% w/v). Viscosity measurements were
      conducted with a viscometer. Lenticular levels of 2-MS were determined in the
      lenses from young Sprague Dawley rats receiving 1 drop of selected topical
      suspension twice-daily for 7 days. The efficacy of the suspensions to arrest
      sugar cataract formation was evaluated by administering the suspensions for 21
      days to similar rats fed a diet containing 50% galactose. Lens changes were
      examined by portable slit lamp following mydriasis. RESULTS: Lenticular levels of
      2-MS was highest in rats administered suspensions containing 0.25% carbopol +
      0.25% HPMC as vehicles followed by 0.5% gellan gum, 0.5% HPMC, 0.25% carbopol,
      and 0.5% xanthan gum. All untreated rats fed a 50% galactose diet developed
      hypermature cataracts within 15 days; however, none of the topical treated rats
      demonstrated cortical vacuole formation after 21 days of galactose feeding.
      CONCLUSIONS: In the suspensions examined, no direct relationship between the
      lenticular drug levels of 2-MS and either viscosity or pH of the vehicles were
      observed. The observed arrest of sugar cataract formation indicated that
      therapeutically adequate lenticular levels of 2-MS were provided by all topical
      suspensions.

PMID- 17444800
TI  - A modified in vitro method for aqueous humor outflow studies in enucleated
      porcine eyes.
AB  - The aim of this study was to develop and test a short-term in vitro method for
      aqueous humour outflow studies using enucleated porcine eyes. The method used was
      a modification of two methods that have previously been used: whole eyes and
      anterior segment cultures. The advantage of the model used in this study was that
      the anterior part of the eye, including the anterior and posterior chambers,
      remained intact as in whole enucleated eyes, but neither iridotomia nor
      trephination through the cornea was needed. The deepening of the anterior chamber
      during perfusion was avoided by regulating the "vitreal" pressure. Test compounds
      were administered topically or intracamerally to an anatomically normal anterior
      chamber. Fresh porcine eyes (n = 48) were sectioned at the equator, and the
      vitreous mass was carefully removed. This anterior bisection was bound around a
      specific plastic chamber, thus creating a closed eye. The anterior chamber was
      perfused at a pressure of 15 mmHg. The mean outflow rate in the nonmedicated eye
      group was 3.7 +/- 0.20 microL/min (mean +/- standard error of the mean), and it
      increased by 18% during 9 h owing to a wash-out effect. Compounds known to
      enhance the aqueous outflow were used for testing the validity of the
      preparation.

PMID- 17444801
TI  - Evaluation of the vascular targeting agent combretastatin a-4 prodrug on retinal
      neovascularization in the galactose-fed dog.
AB  - PURPOSE: Combretastatin A-4 (CA-4) is a vascular targeting agent known to rapidly
      shut off blood flow in new vessels and, as a result, regress neovascularization.
      In this pilot study, the ability of CA-4 to modify retinal neovascularization,
      which results in altered retinal vessel blood flow and retinal permeability, was
      evaluated in aphakic long-term galactose-fed beagles, an animal model that
      develops diabetes-like retinal neovascularization. METHODS: Two (2) groups of
      aphakic dogs, each group comprised of 4 galactose-fed dogs and 2 age-matched
      controls dogs, were utilized. Each group initially received the combretastatin A
      4-phosphate prodrug (CA-4P) as either sub-Tenon's injections, administered at the
      corneoscleral junction, or intravitreal injections. Six (6) weeks after this
      treatment, all dogs also received systemic (intravenous) injections of CA-4P.
      Retinal vascular changes were monitored at 2-week intervals by fluorescein
      angiography. RESULTS: All galactose-fed dogs demonstrated the presence of retinal
      neovascular lesions by fluorescein angiograms. Fluorescein leakage or perfusion
      through neovascular vessels was not altered by either sub-Tenon's, intravitreal,
      or systemic CA-4P administration. Whereas CA-4P was well tolerated by the healthy
      eyes of the control animals, its administration to some galactose-fed dogs was
      associated with corneal edema and increases in intraocular pressure following sub
      Tenon's and intraocular injections. CONCLUSIONS: Neovascularization in the
      galactose-fed dog progresses over a period of years, similar to that observed
      with clinical diabetic retinopathy. The failure of CA-4P to ameliorate
      neovascularization suggests that chronic, long-term administration may be
      required to destroy the slowly growing retinal endothelial cells.

PMID- 17444802
TI  - Tumor-volume increase at beginning of primary treatment with topical interferon
      alpha 2-beta in a case of conjunctiva-cornea intraepithelial neoplasia.
AB  - AIMS: The aim of this study was to report on the effectiveness and tumor side
      effects of topical interferon (INF) alpha 2-beta in a case of conjunctiva-cornea
      intraepithelial neoplasia (CIN) of a patient that rejected any surgical
      procedure. METHODS: This study is a case report description. RESULTS: An 81-year
      old man with a history of neoplasies of the colon and prostate and anticoagulant
      treatment was referred for treatment of an ocular surface neoplasia on his left
      eye. Pathognomonic signs of CIN were present. The patient rejected surgical
      procedures. A regimen of topical INF alpha 2-beta 4 times daily was administered.
      An increase in tumor volume of 25% was observable 15 days after the beginning of
      therapy. No subjective discomfort was reported. The treatment continued with
      follow-ups every 15 days. The progressive regression was remarkable. Complete
      regression of the CIN was observable after 60 days of therapy. No other side
      effects were detected. CONCLUSIONS: Topical INF alpha 2-beta is a valid choice
      for the treatment of CIN in patients for whom surgery is not possible. The
      increase of tumor volume at the beginning of therapy does not require the
      suspension of treatment.

PMID- 17444803
TI  - In vitro diffusion of the immunosuppressant tacrolimus through human and rabbit
      corneas.
AB  - PURPOSE: The aim of this study was to investigate the in vitro diffusion kinetics
      of tacrolimus (TAC) through rabbit and human corneas, and to evaluate the
      suitability of rabbit cornea as an in vitro permeability model for human cornea.
      METHODS: A flow-through diffusion apparatus was used for all permeability
      experiments. The percentage of total (3)H-TAC diffusing across the corneas was
      determined over 24 h and fractions collected twice-hourly (20 degrees C; 1.5
      mL/h). An F test was used for whole-curve comparisons, with a significance level
      of 5%. RESULTS: Steady-state values for TAC across both types of corneas were not
      reached. Although the percentage of TAC diffusing across rabbit cornea was higher
      than that found for human cornea up to 18 h, there were no statistically
      significant differences. The percentages of total TAC diffusing across human and
      rabbit cornea at the 24-h time points were 0.38% +/- 0.02% and 0.36% +/- 0.01%,
      respectively. CONCLUSIONS: Percentages of total TAC at the 24-h time points were
      approximately 4.9x and 4.1x higher than those found previously for cyclosporin A
      across human and rabbit corneas, respectively. Rabbit corneas are a suitable
      model for human corneas in in vitro permeability studies.

PMID- 17444804
TI  - Aloe-emodin metabolites protected N-methyl-d-aspartate-treated retinal ganglion
      cells by Cu-Zn superoxide dismutase.
AB  - A high concentration of glutamate in the eyes not only activates N-methyl-D
      aspartate (NMDA) receptors, but also is toxic to the retina ganglion cells (RGCs)
      in glaucomatous patients. Our previous study had found that aloe-emodin
      sulfates/glucuronides metabolites, an anthraquinone polyphenol, exerted a
      neuroprotective activity upon RGCs. In order to understand the mechanisms
      involved in this neuroprotective effect, this study aimed to determine the
      expressions of RNAs and proteins in various treatments. The proteins expressed in
      the control group, NMDA-treated group, and aloe-emodin metabolites-cotreated
      group were separated by two-dimensional gel electrophoresis (2-DE). Protein spots
      were excised from 2-DE and analyzed by nano-LC-MS/MS (nano-liquid chromatography
      with mass spectrometry; tandem MS). Quantitative polymerase chain reaction (Q
      PCR) was used to investigate the RNA related to these proteins. There were 84
      spots with significant differences in various treatments. Among the 84 spots, we
      identified 9 spots whose functions were closely related to regulate the apoptosis
      of cells. The results of Q-PCR were not completely unanimous with those of 2-DE.
      Our results suggested that aloe-emodin metabolites decreased NMDA-induced
      apoptosis of RGCs by preserving, and inducing, some proteins related to the
      antioxidation and regulation of cells' energy. Both the level of RNA and protein
      of superoxide dismutase (Cu-Zn) were significantly elevated after aloe-emodin
      metabolites were added. The mechanisms of neuroprotection are complicated, and
      involve not only the transcription and stability of mRNA, but also post
      translation protein modifications, degradation, and protein-protein interaction.

PMID- 17444805
TI  - Expression of ABC-transporters in human corneal tissue and the transformed cell
      line, HCE-T.
AB  - PURPOSE: The aim of this study was to elucidate the expression pattern of
      transport proteins relevant to drug absorption in human cornea and to assess the
      human corneal epithelial cell line, HCE-T, regarding its use as an in vitro model
      for drug-absorption studies. METHODS: Human corneal tissue and HCE-T cells were
      examined for the expression of P-glycoprotein (P-gp/MDR1), multidrug resistance
      associated protein 1 (MRP1), multidrug resistance-associated protein 2 (MRP2),
      lung resistance-related protein (LRP), and breast cancer-resistance protein
      (BCRP), using reverse transcriptase-polymerase chain reaction and
      immunofluorescence microscopy. Moreover, transporter activity was measured by bi
      directional flux studies across excised human cornea and HCE-T cell layers using
      a P-gp/MDR1 substrate, rhodamine 123 (Rh123). RESULTS: Transport studies of Rh123
      revealed no significant differences in fluxes in the apical-to-basolateral and
      basolateral-to-apical directions across excised human corneas or HCE-T cell
      layers, suggesting the absence or insignificant, if any, participation of P
      gp/MDR1 to Rh123 fluxes. Of all the transporter proteins under investigation,
      only LRP was found in human cornea. By contrast, a signal for LRP was not found
      in HCE-T, but the expression of MRP1, MRP2, and BCRP could be confirmed. Of note
      is the lack of P-gp/MDR1 expression in any of the specimens we examined.
      CONCLUSIONS: Only a limited array of ABC-transporters is functionally expressed
      in human cornea. The expression pattern of HCE-T cells appears to be widely
      different from that of the native corneal tissue. Hence, the in vitro model of
      human cornea, HCE-T, should be used with much caution when predicting transport
      rates across the human corneal epithelial barrier in vivo.

PMID- 17444806
TI  - Comparative analysis of prednisolone acetate suspensions.
AB  - PURPOSE: The aim of this study was to determine differences in particle size
      between three prednisolone acetate suspensions: Pred Forte, EconoPred Plus, and
      generic prednisolone acetate 1%. SETTING: This study employed the setting of a
      laboratory evaluation. METHODS: Qualitative assessment of sedimentation rate as a
      function of particle size was the method employed for this study. Samples of the
      three products were taken from the top of the suspensions at 0 and 6 h and then
      at 12-h intervals from 12 to 72 h. At 72 h, a sample was pulled from the bottom
      of each suspension. RESULTS: Particle size in aliquots removed from the top of
      the suspensions steadily decreased over time. In the Pred Forte sample, results
      for 72 h (bottom) were consistent with T = 0 h results. In the generic and
      EconoPred Plus lots, the T = 72 h (bottom) results exceeded the T = 0 h results,
      suggesting a tendency for these particles to agglomerate more readily.
      CONCLUSIONS: The prednisolone particles in Pred Forte were smaller and more
      uniform at all time points, allowing them to stay in suspension longer. This may
      result in greater homogeneity between doses and increased ocular bioavailability.

PMID- 17444807
TI  - Susceptibility of the ocular lens to nitric oxide: implications in
      cataractogenesis.
AB  - Oxides of nitrogen, such as nitric oxide (NO), are now biologically referred to
      as reactive nitrogen species. The generation of NO gives rise to several other
      reactive species, such as NO+, NO-, NO2, N2O3, and ONOO- and so forth, which are
      all capable of inflicting tissue damage. Indeed, NO generation is known to be
      associated with retinal degeneration and glaucoma. Its level has also been found
      to increase in the aqueous and vitreous humors in diabetes. We hypothesize that
      such an increase would have a detrimental effect on the biochemistry and
      metabolism of tissues, including the lens, bathed by the aqueous containing
      elevated levels of NO. The primary aim of our investigations was, therefore, to
      examine the susceptibility of the lens to damage by NO in vitro in the presence
      of nitroaspirin, a novel NO donating agent. The extent of physiologic damage to
      the lens was initially assessed by determining the integrity of its active
      transport mechanism. The overall status of tissue metabolism was determined by
      measuring the adenosine triphosphate (ATP) levels. The levels of glutathione
      (GSH) and glutathione disulfide, reflecting the status of its antioxidant
      reserve, were also determined. That NO is indeed deleterious to the lens was
      apparent by the inhibition of the active transport of Rb(+). This was associated
      with a substantial decrease in the contents of ATP and GSH, the decrease in the
      latter directly suggesting that the NO effects are caused by oxidative stress.
      That the effects are caused by NO generated from nitroaspirin was proven by a
      substantial increase in NO level in the medium during incubation of the lenses
      with nitroaspirin, as compared to the controls. The results, therefore, were
      highly suggestive of a contribution of the oxides of nitrogen in cataract
      formation associated with diabetes and other aging diseases.

PMID- 17444808
TI  - Impact of administration angle on the cost of artificial tear solutions: does
      bottle positioning minimize wastage?
AB  - PURPOSE: The aim of this study was to describe the cost considerations of
      multidose artificial tear products according to drop volume and the number of
      usable drops per bottle, based on a 45- versus 90-degree administration angle.
      METHODS: Densitometric assessment of the drop volume of five multidose artificial
      tear products of a 15-mL labeled bottle size in conjunction with predictive cost
      analysis. RESULTS: The correlation between drop volume and density was not
      significant (Spearman correlation, P = 0.4500; alpha < 0.05). Overall, drop size
      ranged from 65.9 microL to a nadir of 30.8 microL, with a statistically
      significant difference (Student t test, P < 0.05) between 45- and 90-degree
      volumes for all but one product. Cost analysis demonstrated up to a $1.93 per
      bottle cost savings by the administration of drops at a 45- rather than a 90
      degree bottle angle. CONCLUSIONS: Products that provide a higher number of drops
      per dollar of product offer economic advantages that may not be otherwise
      discernible by the examination of the product retail price alone. Furthermore, it
      is shown that altering the angle of administration may, in general, result in
      significant economic ramifications in the use of multidose artificial tear
      products longitudinally.

PMID- 17444809
TI  - Hypotony and choroidal detachment as a complication of topical combined timolol
      and dorzolamide.
AB  - PURPOSE: Hypotony with choroidal detachment is a rare complication of glaucoma
      medication. In this study, we report on a case which supports the hypothesis that
      has been proposed to explain this phenomenon. DESIGN: This study was designed as
      an observational case report. CASE REPORT: A woman with chronic glaucoma
      underwent trabeculectomy on both eyes. Low intraocular pressure (IOP) developed
      in 1 eye only, with no visual change for many years. After cataract surgery, the
      IOP increased, necessitating treatment with topical timolol 0.5% and dorzolamide
      2%. She developed monocular hypotony and choroidal detachment 3 months later.
      This complication occurred in the eye that had previously had a low IOP and
      resolved completely when topical medication was stopped. The choroidal detachment
      recurred when rechallenged with the same medication. CONCLUSIONS: Topical aqueous
      suppression therapy can result in hypotony and choroidal detachment in an eye in
      which relatively low IOP has been maintained for many years after glaucoma
      filtration surgery. The problem resolves on stopping the medication.

PMID- 17444810
TI  - Noninvasive human brain stimulation.
AB  - Noninvasive brain stimulation with transcranial magnetic stimulation (TMS) or
      transcranial direct current stimulation (tDCS) is valuable in research and has
      potential therapeutic applications in cognitive neuroscience, neurophysiology,
      psychiatry, and neurology. TMS allows neurostimulation and neuromodulation, while
      tDCS is a purely neuromodulatory application. TMS and tDCS allow diagnostic and
      interventional neurophysiology applications, and focal neuropharmacology
      delivery. However, the physics and basic mechanisms of action remain incompletely
      explored. Following an overview of the history and current applications of
      noninvasive brain stimulation, we review stimulation device design principles,
      the electromagnetic and physical foundations of the techniques, and the current
      knowledge about the electrophysiologic basis of the effects. Finally, we discuss
      potential biomedical and electrical engineering developments that could lead to
      more effective stimulation devices, better suited for the specific applications.

PMID- 17444811
TI  - The genetic lexicon of dyslexia.
AB  - Reading abilities are acquired only through specific teaching and training. A
      significant proportion of children fail to achieve these skills despite normal
      intellectual abilities and an appropriate opportunity to learn. Difficulty in
      learning to read is attributable to specific dysfunctions of the brain, which so
      far remain poorly understood. However, it is recognized that the neurological
      basis for dyslexia, or reading disability, is caused in large part by genetic
      factors. Linkage studies have successfully identified several regions of the
      human genome that are likely to harbor susceptibility genes for dyslexia. In the
      past few years there have been exciting advances with the identification of four
      candidate genes located within three of these linked chromosome regions: DYX1C1
      on chromosome 15, ROBO1 on chromosome 3, and KIAA0319 and DCDC2 on chromosome 6.
      Functional studies of these genes are offering new insights about the biological
      mechanisms underlying the development of dyslexia and, in general, of cognition.

PMID- 17444814
TI  - Effect of 2-methylene-19-nor-(20S)-1 alpha-hydroxy-bishomopregnacalciferol
      (2MbisP), an analog of vitamin D, on secondary hyperparathyroidism.
AB  - Vitamin D analogs are being developed that retain therapeutic effects but are
      less calcemic and phosphatemic, a concern in CKD patients who are prone to
      vascular calcification. We tested a new analog of vitamin D, 2MbisP, and found
      that it suppresses PTH at doses that do not affect serum Ca or P. INTRODUCTION:
      Calcitriol is used for the treatment of secondary hyperparathyroidism. However,
      its use is often limited by the development of hypercalcemia and
      hyperphosphatemia, an important consideration in patients with chronic kidney
      disease (CKD) because they are prone to vascular calcification. To minimize this
      toxicity, structural modifications in the vitamin D molecule have led to the
      development of calcitriol analogs with selective actions. MATERIALS AND METHODS:
      In this study, we compared the effects of 1,25(OH)(2)D(3) and a new analog, 2
      methylene-19-nor-(20S)-1 alpha-hydroxy-bishomopregnacalciferol (2MbisP), on the
      development of secondary hyperparathyroidism and established secondary
      hyperparathyroidism in uremic rats and on mobilization of calcium and phosphorus
      from bone in parathyroidectomized rats. The clearance from circulation, half
      life, and binding affinities to the vitamin D-binding protein and vitamin D
      receptor of this compound were also evaluated. RESULTS: Uremia produced a marked
      rise in plasma PTH, but treatment every other day for 2 wk with either
      1,25(OH)(2)D(3) (4 ng) or 2MbisP (250, 750, 1500, or 3000 ng) suppressed this
      increase by >50%. The suppression by 1,25(OH)(2)D(3), however, was accompanied by
      increases in ionized calcium, phosphorus, and the calcium x phosphorus product,
      whereas these three parameters were unchanged by 2MbisP. The binding affinity of
      2MbisP was 10-20 times less for the vitamin D receptor and 1000 times less for
      the serum vitamin D-binding protein compared with 1,25(OH)(2)D(3). Also, 2MbisP
      was cleared more rapidly from the circulation (t1/2 = 10 min) than 1,25
      (OH)(2)D(3) (t1/2=7-9 h). In parathyroidectomized rats fed calcium-or phosphorus
      deficient diets, daily injections of 2MbisP (1500 or 3000 ng), unlike
      1,25(OH)(2)D(3) (50 ng), had no effect on calcium or phosphorus mobilization from
      bone. CONCLUSIONS: In uremic rats, 2MbisP can suppress PTH at doses that do not
      affect plasma calcium, phosphorus, and calcium x phosphorus product. This new
      vitamin D analog may represent an important tool in the treatment of secondary
      hyperparathyroidism in patients with CKD.

PMID- 17444812
TI  - Taste receptor genes.
AB  - In the past several years, tremendous progress has been achieved with the
      discovery and characterization of vertebrate taste receptors from the T1R and T2R
      families, which are involved in recognition of bitter, sweet, and umami taste
      stimuli. Individual differences in taste, at least in some cases, can be
      attributed to allelic variants of the T1R and T2R genes. Progress with
      understanding how T1R and T2R receptors interact with taste stimuli and with
      identifying their patterns of expression in taste cells sheds light on coding of
      taste information by the nervous system. Candidate mechanisms for detection of
      salts, acids, fat, complex carbohydrates, and water have also been proposed, but
      further studies are needed to prove their identity.

PMID- 17444815
TI  - Effects of genes, sex, age, and activity on BMC, bone size, and areal and
      volumetric BMD.
AB  - Quantitative genetic analyses of bone data for 710 inter-related individuals 8-85
      yr of age found high heritability estimates for BMC, bone area, and areal and
      volumetric BMD that varied across bone sites. Activity levels, especially time in
      moderate plus vigorous activity, had notable effects on bone. In some cases,
      these effects were age and sex specific. INTRODUCTION: Genetic and environmental
      factors play a complex role in determining BMC, bone size, and BMD. This study
      assessed the heritability of bone measures; characterized the effects of age,
      sex, and physical activity on bone; and tested for age- and sex-specific bone
      effects of activity. MATERIALS AND METHODS: Measures of bone size and areal and
      volumetric density (aBMD and vBMD, respectively) were obtained by DXA and pQCT on
      710 related individuals (466 women) 8-85 yr of age. Measures of activity included
      percent time in moderate + vigorous activity (%ModVig), stair flights climbed per
      day, and miles walked per day. Quantitative genetic analyses were conducted to
      model the effects of activity and covariates on bone outcomes. RESULTS:
      Accounting for effects of age, sex, and activity levels, genes explained 40-62%
      of the residual variation in BMC and BMD and 27-75% in bone size (all p<0.001).
      Decline in femoral neck (FN), hip, and spine aBMD with advancing age was greater
      among women than men (age-by-sex interaction; all p <or= 0.05). %ModVig had the
      most notable effect on bone; high activity was associated with higher aBMD at all
      sites, but the magnitude of this effect varied. Activity among men was associated
      with higher FN BMC and cross-sectional area (CSA) at the 4% radius, but this was
      not observed among women (sex-by-activity interaction, both p <or= 0.05). Younger
      women had greater cortical vBMD (Cort-vBMD) than younger men, with minimal
      difference between low and high activity levels. Influence of activity was
      greater in older women: older women with low activity had lower Cort-vBMD than
      older men, but older women with high activity had higher Cort-vBMD than older men
      (age-by-sex-by-activity interaction, p=0.04). CONCLUSIONS: High heritability
      estimates for DXA and pQCT measures varied across bone sites. Percent time spent
      in moderate to vigorous activity had the most notable effect on bone, and in some
      cases, this effect was age or sex specific.

PMID- 17444813
TI  - The ketogenic diet and brain metabolism of amino acids: relationship to the
      anticonvulsant effect.
AB  - In many epileptic patients, anticonvulsant drugs either fail adequately to
      control seizures or they cause serious side effects. An important adjunct to
      pharmacologic therapy is the ketogenic diet, which often improves seizure
      control, even in patients who respond poorly to medications. The mechanisms that
      explain the therapeutic effect are incompletely understood. Evidence points to an
      effect on brain handling of amino acids, especially glutamic acid, the major
      excitatory neurotransmitter of the central nervous system. The diet may limit the
      availability of oxaloacetate to the aspartate aminotransferase reaction, an
      important route of brain glutamate handling. As a result, more glutamate becomes
      accessible to the glutamate decarboxylase reaction to yield gamma-aminobutyric
      acid (GABA), the major inhibitory neurotransmitter and an important antiseizure
      agent. In addition, the ketogenic diet appears to favor the synthesis of
      glutamine, an essential precursor to GABA. This occurs both because ketone body
      carbon is metabolized to glutamine and because in ketosis there is increased
      consumption of acetate, which astrocytes in the brain quickly convert to
      glutamine. The ketogenic diet also may facilitate mechanisms by which the brain
      exports to blood compounds such as glutamine and alanine, in the process favoring
      the removal of glutamate carbon and nitrogen.

PMID- 17444819
TI  - Strengthening behavioural interventions for Indigenous health.

PMID- 17444818
TI  - PTEN is destabilized by phosphorylation on Thr366.
AB  - Although PTEN (phosphatase and tensin homologue deleted on chromosome 10) is one
      of the most commonly mutated tumour suppressors in human cancers, loss of PTEN
      expression in the absence of mutation appears to occur in an even greater number
      of tumours. PTEN is phosphorylated in vitro on Thr366 and Ser370 by GSK3
      (glycogen synthase kinase 3) and CK2 (casein kinase 2) respectively, and specific
      inhibitors of these kinases block these phosphorylation events in cultured cells.
      Although mutation of these phosphorylation sites did not alter the phosphatase
      activity of PTEN in vitro or in cells, blocking phosphorylation of Thr366 by
      either mutation or GSK3 inhibition in glioblastoma cell lines led to a
      stabilization of the PTEN protein. Our data support a model in which the
      phosphorylation of Thr366 plays a role in destabilizing the PTEN protein.

PMID- 17444820
TI  - Group A streptococcal infections in children.
AB  - The group A streptococcus causes the widest range of disease in humans of all
      bacterial pathogens. Group A streptococcal diseases are more common in children
      than adults with diseases ranging from pharyngitis and impetigo to invasive
      infections and the post-streptococcal sequelae--acute rheumatic fever and acute
      post-streptococcal glomerulonephritis. The global burden of severe group A
      streptococcal disease is concentrated largely in developing countries and
      Indigenous populations such as Aboriginal Australians. Control of group A
      streptococcal disease is poor in these settings and the need for a vaccine has
      been argued. With an ever-increasing understanding of the group A streptococcus
      at a molecular level, new and sophisticated vaccines are currently in human
      trials and the next decade holds exciting prospects for curbing group A
      streptococcal diseases.

PMID- 17444821
TI  - Egg allergy: are all childhood food allergies the same?
AB  - Egg allergy is one of the most common food allergies in childhood affecting about
      1-2% of preschool children and differs in a number of ways from other common
      childhood food allergies such as cows milk and peanut. Common egg allergens are
      altered both by heat and gastric enzymes. Compared with peanuts/tree nuts and
      milk, egg allergy appears less likely to cause severe life-threatening reactions
      or fatal anaphylaxis. Children are much more likely to outgrow egg allergy by
      school age as compared with peanut allergy. While the MMR vaccine is no longer
      contraindicated in egg allergy, influenza vaccine is contraindicated in children
      with anaphylaxis to egg. An understanding of the similarities and differences in
      these common food allergies of childhood is helpful in the management of these
      common and increasing problems.

PMID- 17444822
TI  - Inherited cancer susceptibility syndromes in paediatric practice.
AB  - Over the last decade there have been rapid advances in our knowledge about the
      molecular basis of many inherited disorders. Molecular testing is now available
      for many conditions and may assist in the management of the individual and their
      extended family. One area where the use of genetic testing has expanded rapidly
      is in the area of hereditary cancer, particularly in relation to hereditary
      breast/ovarian and hereditary bowel cancer syndromes. Although individually
      uncommon, there are also a number of rare cancer susceptibility syndromes
      affecting the paediatric population, where genetic testing may assist in patient
      management. The following review is a practical guide for clinicians about the
      role of genetic testing for some rare tumour susceptibilities pertaining to
      children, including retinoblastoma, familial adenomatous polyposis, juvenile
      polyposis syndromes, Von Hippel-Lindau disease, multiple endocrine neoplasia, Li
      Fraumeni syndrome and neurofibromatosis. We concentrate on disorders where
      germline mutation testing is routinely available and influences patient
      management. We have placed specific emphasis on the paediatric presentation of
      these disorders and provide some guidance to clinicians about surveillance
      protocols in affected individuals and 'at-risk' family members.

PMID- 17444823
TI  - Legal basis for ethical withholding and withdrawing life-sustaining medical
      treatment from infants and children.
AB  - Withholding and withdrawing life-sustaining medical treatment is common in
      hospitals, particularly in intensive care unit environments. Usually, decisions
      regarding limitation of therapy are based on ethical considerations and derived
      by discussion and mutual agreement between parents and clinicians. However,
      disputes sometimes arise. When such disputes are settled in court, the judgements
      constitute common law and may serve as the basis for ethical decisions. All cases
      have been decided in the 'best interests' of the unfortunate child. Although each
      case has its own circumstances, a composite view reveals three legal criteria for
      withholding or withdrawing treatment. These are based on the present and future
      'quality of life', 'futility' of present treatment and a comparison of 'burdens
      versus benefits' of present and future treatment and its discontinuance. These
      legal principles may facilitate difficult ethical decisions. This article
      identifies a number of common law cases which establishes these principles.

PMID- 17444824
TI  - Spinal muscular atrophy type 1: is long-term mechanical ventilation ethical?
AB  - We present a baby with spinal muscular atrophy type 1, an inherited disorder
      causing progressive weakness, leading to complete paralysis of respiratory,
      facial and limb muscles. Without intervention, death occurs in infancy due to
      respiratory failure. Mechanical ventilatory support can prolong life, but the
      child's quality of life is highly debatable. We discuss the appropriateness of
      initiating and continuing intensive care for this child and others in a similar
      position.

PMID- 17444825
TI  - Infant sleep position, head shape concerns, and sleep positioning devices.
AB  - AIM: The Back To Sleep campaign has successfully promoted the use of the supine
      sleep position for infants, with a corresponding decrease in sudden infant death
      syndrome death rates around the world. The aim of this study was to survey
      current infant sleep position practices, concerns about plagiocephaly, and the
      use of sleep positioning devices. METHODS: A postal survey of 400 mothers of
      infants aged 6 weeks to 4 months was carried out in Auckland, New Zealand.
      RESULTS: Of the 278 (69.5%) respondents, the supine position was usually used in
      64.8%, the prone position in 2.9%, with 32.3% using the side position or a
      combination of side and back positions. Approximately one-third had a concern
      about their infant's head shape, and 80% described practices to help prevent head
      deformation. Thirty per cent reported they had changed their infant's sleep
      position because of head shape concerns. A third of the mothers used some sort of
      positioning system to maintain the infant's sleep position. CONCLUSIONS:
      Anxieties about plagiocephaly, aspiration of vomit, and poor quality sleep are
      the main concerns that parents have about sleeping their infants on their backs.
      Further education is needed to inform mothers about these issues and to alleviate
      their fears.

PMID- 17444826
TI  - Factors influencing breastfeeding rates in south-western Sydney.
AB  - AIM: To explore the socio-demographic factors and other maternal characteristics
      that influence breastfeeding initiation rates. In particular, this paper aims to
      (i) estimate the rate of breastfeeding by maternal socio-demographic factors and
      other maternal characteristics at first well-baby visit; and (ii) investigate the
      relationship between breastfeeding rates and these maternal factors. METHODS:
      Cross-sectional data were obtained for 9618 babies in south-western Sydney in New
      South Wales from the Ingleburn Baby Information Systems database from January
      2000 to June 2004 and included information on breastfeeding status, socio
      demographic factors and other maternal characteristics. RESULTS: At first visit,
      59.8% of mothers were breastfeeding. The factors that increased the risk for NOT
      breastfeeding on multivariate analysis were being Australian-born (OR=1.67, 95%
      CI 1.45-1.89, P<0.001), unmarried (OR=1.79, 95% CI 1.52-2.11, P<0.001), living in
      disadvantaged accommodation (OR=1.90, 95% CI 1.60-2.26, P<0.001), having lower
      levels of education (OR=1.88, 95% CI 1.38-2.54, P<0.001) and current smoking
      (OR=1.72, 95% CI 1.51-1.96, P<0.001). CONCLUSION: The results from this large
      population-based study suggest that breastfeeding rates are significantly
      influenced by socio-demographic factors and maternal characteristics.
      Consequently, subgroups of the population 'at risk' for not breastfeeding can be
      identified and targeted for further strategies to promote breastfeeding.

PMID- 17444827
TI  - Overweight in medical paediatric inpatients: detection and parent expectations.
AB  - AIMS: (i) To determine prevalence and rates of detection of overweight/obesity
      among general paediatric inpatients. (ii) To explore parental expectations
      regarding detection and management of overweight/obesity during admission.
      METHODS: This is a cross-sectional survey conducted in the Royal Children's
      Hospital, Melbourne, Australia. A total of 102 children aged 2-12 years admitted
      to a general paediatric unit at the Royal Children's Hospital and their parents
      participated in the survey. The main outcome measures are body mass index (BMI);
      documentation of weight, height and BMI in patient notes; parent description of
      child's weight, parent concern about child's weight, and parent opinion about
      detection and management of overweight. RESULTS: Twelve of 102 children (11.7%,
      95% confidence intervals 6.2%, 19.7%) were overweight or obese. All children had
      a documented weight, two children (2.0%) had a documented height and none had BMI
      documented. Seven of 12 parents of overweight children described their child's
      weight as healthy; five of 12 parents of overweight children were not concerned
      about their child's weight. Eight of 12 parents of overweight children believed
      all admitted children should have their BMI calculated. All parents thought the
      hospital should take action if a child was found to be overweight. CONCLUSIONS:
      Although prevalence of overweight was lower than expected, documentation of
      overweight did not occur for any patient in the study. Parents of overweight
      children with acute illnesses believed that the hospital should screen for
      overweight and discuss it with parents. Further studies are required to determine
      expectations among other patient populations.

PMID- 17444828
TI  - Psychosocial adjustment and physical health of children living with maternal
      chronic pain.
AB  - AIM: There is limited research examining the functioning of children living with
      parental chronic pain and illness. The aim of this study was to examine the
      psychosocial adjustment and physical health of children living with a mother
      experiencing chronic pain. METHODS: One-hundred and three children aged 6-12
      years served as participants, with approximately equal numbers of children in
      maternal chronic pain (n=55) and control groups (n=48). Children completed self
      reports about their internalising behaviour, health and attachment security.
      Mothers, fathers and teachers completed questionnaires relating to children's
      internalising and externalising behaviour, social behaviour and physical health.
      RESULTS: Reports from children, mothers and fathers indicated significantly more
      internalising, externalising, insecure attachment and social and health problems
      for children in the maternal chronic pain group compared with control children.
      Teachers reported decreased social skills and increased pain complaints for
      children in the maternal chronic pain group. Boys in the maternal chronic pain
      group appear to be affected more than girls. Boys reported more anxiety and
      insecure attachment, while mothers reported greater social problems and increased
      illness behaviour for boys. Characteristics of the mother's pain condition, such
      as, severity, length and frequency were generally unrelated to child functioning.
      CONCLUSIONS: The study demonstrates the importance of maternal and family
      variables to child outcomes. The results are discussed in terms of maternal
      chronic pain comprising a considerable, yet rarely studied, influence in the
      lives of young children.

PMID- 17444829
TI  - Ordering of renal tract imaging by paediatricians after urinary tract infection.
AB  - AIM: To describe paediatricians' reported ordering of renal tract imaging of
      children following urinary tract infection. METHODS: This is a piloted self
      administered survey. A total of 354 randomly sampled practising paediatricians in
      Australia participated in the survey. The survey included 12 clinical scenarios
      that varied with age, gender and fever. Respondents indicated their likelihood of
      ordering renal ultrasound, micturating cystourethrogram (MCU) and
      dimercaptosuccinic acid scan (DMSA) from 0 to 100%. RESULTS: Response rate was
      74.6% (264/354). For all clinical scenarios the median probability of ordering an
      ultrasound was 100% with little variability. For children aged 2 months,
      likelihood of ordering an MCU was 100%, with little variability, but was 70% for
      3-year-olds with fever (45% without fever), and 5% for 6-year-olds with very
      large variability. Median likelihood of ordering a DMSA was 80% at 2 months, 60%
      at 3 years and 20% at 6 years (40%, 15%, 5% without fever, respectively).
      Variability was large for all scenarios and DMSA ordering. Child gender did not
      influence ordering practices. CONCLUSIONS: Renal tract imaging practice across
      paediatricians shows consistent, approximately 100% use of the least invasive
      modality, ultrasound. In contrast, there is considerable variation in the
      reported ordering of the more invasive tests MCU and DMSA. Doctors order these
      tests more in younger children and when fever is present.

PMID- 17444830
TI  - Personality profiles and pulmonary function of children with sighing dyspnoea.
AB  - AIM: This study compared the personality profiles of children with sighing
      dyspnoea with healthy children and tested the hypothesis of heightened anxiety
      scores in sighing dyspnoeic subjects using the Childhood Behavior Check List for
      Ages 4 to 18 (CBCL/4-18). The pulmonary function tests of these two groups of
      children were also compared. METHODS: This prospective study enrolled paediatric
      patients with sighing dyspnoea presented to a paediatric pulmonary clinic but
      free from apparent cardiopulmonary diseases, and age-matched healthy children
      were recruited for comparison. The psychological profiles of the patients were
      collected by the CBCL/4-18, which was completed by the parents. Spirometry was
      performed on sighing children as well as volunteer healthy children, before and
      after bronchodilator. RESULTS: Twenty patients complained of sighing dyspnoea and
      31 healthy children were included in the study. Both groups of children scored
      consistently within the normal ranges of all subscales including anxiety, somatic
      complaints or internalising behaviour on CBCL/4-18. The t-scores were not
      significant different between children with sighing dyspnoea and age-matched
      controls. Baseline forced vital capacity in the sighing patients appeared to be
      lower than the healthy children, but was not statistically significant.
      CONCLUSIONS: The CBCL/4-18 scores of children with sighing dyspnoea were not
      significant different from age-matched healthy children and a heightened anxiety
      score was not confirmed in this study. Office spirometric values in patients with
      sighing dyspnoea were normal.

PMID- 17444831
TI  - Early infant crying and sleeping problems: a pilot study of impact on parental
      well-being and parent-endorsed strategies for management.
AB  - AIMS: Infant sleeping and crying problems are common and impact adversely on
      maternal mental health but their impact on paternal mental health is unknown. A
      consistent approach to managing such problems has not been identified. Parents
      may be able to identify useful management strategies, which could then inform the
      content of a prevention/early intervention approach to such problems. We aimed to
      determine the impact of infant behaviour problems on maternal and paternal mental
      health and management strategies that parents find useful. METHODS:  DESIGN: Pre
      post intervention pilot. SETTING: Paediatric outpatient clinic at the Royal
      Children's Hospital, Melbourne. PARTICIPANTS: 71 mothers and 60 fathers of
      infants aged 2 weeks to 7 months recruited from July 2004 to April 2005. MAIN
      OUTCOME MEASURES: Pre and post questionnaires measuring maternal and paternal
      well-being (Edinburgh Postnatal Depression Scale (EPDS)), parent report of infant
      behaviour problems, usefulness of consultation strategies. RESULTS: Three weeks
      post consultation, fewer parents reported that their infant's behaviour was still
      a problem (64% of mothers and 55% of fathers). Thirty per cent fewer mothers
      reported an EPDS score>12 (45% pre vs. 15% post clinic) while 11% fewer fathers
      reported an EPDS score>9 (30% pre vs. 19% post clinic). Most parents (80% or
      more) rated exclusion of medical causes and information about normal
      sleeping/crying as useful. CONCLUSIONS: Problem infant behaviours are associated
      with poor parental mental health. An intervention/prevention approach to infant
      behaviour problems should include fathers and contain information about normal
      infant sleeping and crying patterns and exclusion of medical causes.

PMID- 17444832
TI  - Relationship between fluid management, changes in serum sodium and outcome in
      hypernatraemia associated with gastroenteritis.
AB  - OBJECTIVE: To describe the relationship between fluid management, serum sodium
      and outcome in critically ill children with hypernatraemic gastroenteritis.
      METHODS: A retrospective study of 57 children with hypernatraemic gastroenteritis
      admitted to a paediatric intensive care unit in Cape Town, South Africa. Data
      were collected on fluid management, serum electrolytes and adverse outcome
      (seizures, new neurological deficit and mortality) and analysed using univariate
      and multivariate statistics. RESULTS: Median admission sodium was 165 mmol/L (145
      199). Median volume of intravenous rehydration fluid was 6 mL/kg/h (144
      mL/kg/day), with sodium concentration of 61 mmol/L (0-154 mmol/L), resulting in a
      median fall in sodium of 0.6 mmol/L/h (14.4 mmol/L/day). Fourteen children (25%)
      had seizures during rehydration, four children (7%) died and five children (9%)
      developed neurological deficit. Median admission sodium in children with adverse
      outcome was 172 mmol/L, with rate of fall of 0.63 mmol/L/h, compared with median
      admission sodium of 163 mmol/L and rate of fall of 0.48 mmol/L/h, in children
      with good outcome (P=0.068 and P=0.08, respectively). Median sodium content of
      intravenous solution was 61 mmol/L in both groups (P=0.68). Multivariate analysis
      demonstrated that neither sodium content of intravenous solution (P=0.59), nor
      rate of fall of sodium (P=0.31), was independently associated with adverse
      outcome. CONCLUSIONS: Rehydration in hypernatraemic gastroenteritis using
      intravenous solutions containing 61 mmol/L sodium would be expected to correct
      serum sodium at a rate of approximately 0.6 mmol/L/h. Neither sodium content of
      the intravenous solution, nor rate of correction of sodium, was independently
      associated with adverse outcome.

PMID- 17444833
TI  - Prediction of severe hyperbilirubinaemia using the Bilicheck transcutaneous
      bilirubinometer.
AB  - OBJECTIVES: To determine the sensitivity and specificity of different levels of
      bilirubin measured by the transcutaneous bilirubinometer Bilicheck on forehead
      and sternum for predicting severe hyperbilirubinaemia of total serum bilirubin
      (TSB)>or=300 micromol/L in Malay, Chinese and Indian infants. DESIGN: A
      prospective observational study. SETTING: A tertiary care University hospital.
      METHODS: A total of 345 healthy jaundiced term infants were recruited prior to
      commencement of phototherapy or exchange transfusion. Transcutaneous bilirubin
      (TcB) level was measured with the Bilicheck from infants' foreheads (TcBh) and
      sternums (TcBs) within 30 min of serum bilirubin measurement by the diazo method
      in the hospital laboratory. RESULTS: The median serum TSB level of these infants
      was 233.0 micromol/L (range: 108.0-589.0). Ninety-five (27.5%) infants had
      TSB>or=300 micromol/L. There was good correlation between log10TSB and TcB
      measured from the forehead (r=0.80, P<0.0001) and the sternum (r=0.86, P<0.0001).
      At TcBh cut-off of 250 micromol/L, the Bilicheck detected TSB>or=300 micromol/L
      with a sensitivity of 100% and a specificity of 39.2%, the area under the
      receiver operative characteristic curve being 0.89 (95% confidence interval 0.85,
      0.92). At TcBs cut-off of 200 micromol/L, the Bilicheck detected TSB>or=300
      micromol/L with a sensitivity of 100% and a specificity of 33.6%, the area under
      receiver operative characteristic curve being 0.93 (95% confidence interval 0.90,
      0.96). CONCLUSION: The Bilicheck is not a substitute for measuring serum
      bilirubin. However, using predetermined TcB cut-off values with reasonable
      sensitivity and specificity, it is a useful screening tool to identify infants
      with TSB>or=300 micromol/L requiring blood sampling, hospital admission and
      treatment.

PMID- 17444834
TI  - Antenatal dexamethasone and renal vascular resistance in preterm infants.
AB  - OBJECTIVE: To compare vascular resistance, renal volume and insulin levels in
      preterm infants with and without antenatal steroids. METHODS: We studied 61
      preterm infants (37 with (group A) and 24 without antecedent of antenatal
      steroids (group B)). We measured insulin levels at birth in cord blood samples.
      Ultrasound measurements to evaluate renal arteries resistance index and renal
      volume were performed during the first 72 h of birth. RESULTS: Preterm infants
      from group A tended to have lower weight and gestational age than those from
      group B. Resistance index in renal arteries was lower in preterm infants with
      steroid therapy compared with group B (right renal artery 0.73 vs. 0.80; P=0.001,
      and left renal artery 0.75 vs. 0.79; P=0.01, respectively). Renal volume and
      insulin levels were not different between the groups. In the multiple regression
      analysis for factors associated with resistance index of renal arteries, only
      antenatal steroids use was included in the model (R2=0.13; P=0.003 and R2=0.10;
      P=0.01 for left and right renal arteries, respectively). CONCLUSION: Antenatal
      dexamethasone in preterm infants during the first 72 h of birth seems to decrease
      resistance index in renal arteries without affecting renal volume and insulin
      levels.

PMID- 17444835
TI  - Bony lesions in BCG-vaccinated children: consider BCG osteitis.
AB  - This instructive case describes a 31-day-old female infant presenting with left
      elbow swelling. Radiographs were initially consistent with non-accidental injury,
      and she was investigated accordingly. After Paediatric Orthopaedic review, BCG
      osteitis was considered as a differential diagnosis. By this time it was too late
      to investigate for this uncommon condition. With the increasing incidence of
      tuberculosis in the Western world, BCG vaccination at birth will become more
      common. This case illustrates the need for multidisciplinary management of bony
      lesions in infants and children, involving paediatricians, orthopaedic surgeons
      and paediatric radiologists.

PMID- 17444836
TI  - Bruising: when it is spontaneous and not idiopathic thrombocytopenia purpura.
AB  - Bruising is a presentation that often causes concern. There are many causes of
      bruising in children, including non-accidental injury, which must be excluded. We
      report a case of a 22-month-old boy where all the common diagnoses were excluded.
      We highlight the need to be aware of transient acquired inhibitors of coagulation
      that can cause spontaneous bleeding.

PMID- 17444837
TI  - Massive hepatic congenital haemangioma: clinical dilemmas.
AB  - A case of massive hepatomegaly secondary to a hepatic congenital haemangioma in a
      preterm neonate is described. This infant died after withdrawal of neonatal
      intensive care support, following massive intracerebral haemorrhage. There
      remains considerable uncertainty regarding the classification of, and therapy
      for, hepatic vascular anomalies.

PMID- 17444838
TI  - Virginal breast hypertrophy of an 11-year-old girl.
AB  - We report a case of an 11-year-old girl with virginal breast hypertrophy; a rare
      condition characterised by rapid breast enlargement in the peripubertal period.
      In this paper we highlight complexities of management in this age group.

PMID- 17444839
TI  - Nosocomial rotavirus infection in an Australian children's hospital.

PMID- 17444840
TI  - Prevalence of overweight and obesity in a regional Queensland preschool
      population.

PMID- 17444841
TI  - Re: critical appraisal of the management of severe malnutrition.

PMID- 17444842
TI  - A boost for child passenger safety.

PMID- 17444844
TI  - New hepatitis C guidelines for the Asia-Pacific region: APASL consensus
      statements on the diagnosis, management and treatment of hepatitis C virus
      infection.

PMID- 17444845
TI  - Targeting chemokines as a therapeutic option for hepatocellular carcinoma: a
      reality or just a fantasy?

PMID- 17444846
TI  - TNF-alpha as therapeutic target in NASH: tried, but not yet proven.

PMID- 17444847
TI  - Asian Pacific Association for the Study of the Liver consensus statements on the
      diagnosis, management and treatment of hepatitis C virus infection.

PMID- 17444848
TI  - Beneficial effects of pentoxifylline on hepatic steatosis, fibrosis and
      necroinflammation in patients with non-alcoholic steatohepatitis.
AB  - BACKGROUND AND AIM: Inhibition of tumor necrosis factor (TNF)-alpha is a logical
      approach to manage patients with non-alcoholic steatohepatitis (NASH).
      Pentoxifylline reduces TNF-alpha and alanine aminotransferase (ALT) levels in
      patients with NASH. The aim of the present paper was to study if pentoxifylline
      can improve histological injury in patients with NASH. METHODS: Nine patients
      (mean age 31.6 +/- 7.2 years) with histologically proven NASH and with
      persistently elevated ALT (>1.5 times) were given pentoxyfylline at a dosage of
      400 mg t.i.d. for 12 months. Besides biochemical assessment, a repeat liver
      biopsy was performed and the degree of inflammation and fibrosis was compared.
      RESULTS: After 12 months of therapy a significant reduction in ALT (111 +/- 53
      IU/L vs 45 +/- 19 IU/L, P = 0.003) and aspartate aminotransferase (AST) (61 +/-
      27 IU/L vs 33 +/- 12 IU/L, P = 0.005) levels was observed. Steatosis and lobular
      inflammation each reduced in 55% and six (67%) patients down-staged on Brunt's
      staging (P = 0.009). Four out of six patients with baseline fibrosis had
      reduction in their fibrosis stage. CONCLUSIONS: Long-term pentoxyfylline therapy
      effectively achieves sustained biochemical improvement. This correlates well with
      histological resolution of the disease.

PMID- 17444849
TI  - Long-term gastroesophageal reflux disease therapy improves reflux symptoms in
      elderly patients: five-year prospective study in community medicine.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) impairs the patient's quality
      of life (QOL), but the effect of long-term maintenance therapy in elderly
      patients is unknown. METHODS: We conducted a long-term prospective study. Forty
      four GERD patients (11 males; mean age 74 years; QUEST score of at least 6
      points) were enrolled in this study. Step-down therapy was selected (proton-pump
      inhibitor [PPI], histamine-2 receptor antagonist and prokinetic agents for 1
      month, respectively). Optimal medication for each patient was continued for 5
      years. The efficacy, safety of treatment and reflux symptoms were analyzed. The
      profiles of the patients who had to continue PPI maintenance therapy were also
      analyzed. RESULTS: Reflux symptoms were reduced by the PPI based step-down
      therapy (baseline 13.8 times/month, after 3.2 times/month, P < 0.001). Reflux
      symptoms improved in 34 patients (77%). None of the 44 patients had to cease
      treatment because of side-effects and none experienced any complications during
      the 5-year period. The prevalence of Helicobacter pylori (Hp) infection in the
      PPI group (29%, 4/14) was significantly lower (P < 0.01) than in the other
      treatment group (72%, 21/29). The serum pepsinogen I/II ratio in the PPI
      treatment group (5.7 +/- 0.5) was significantly higher (P < 0.01) than in the
      others (4.0 +/- 0.3). The predictive factors for PPI maintenance therapy were Hp
      negative status and serum pepsinogen I/II ratio >6.0 (odds ratio 12.0, 95%
      confidence interval 2.7-54.2). CONCLUSIONS: Long-term medication for GERD
      selected on the basis of the patient's profile (i.e. Hp status and gastric
      atrophy) improved reflux symptoms.

PMID- 17444850
TI  - Peginterferon alpha-2a (40 KD) plus ribavirin for the treatment of chronic
      hepatitis C in Japanese patients.
AB  - BACKGROUND: The efficacy and safety of peginterferon alpha-2a (40 KD) (peg
      IFNalpha-2a) plus ribavirin has not been reported for Japanese patients with
      chronic hepatitis C. The aim of this study was to evaluate this combination in
      treatment-naive patients and in non-responders or relapsers to interferon
      monotherapy. METHODS: Overall, 201 treatment-naive patients with hepatitis C
      virus (HCV) genotype-1b were randomly assigned to 180 microg peg-IFNalpha-2a once
      weekly plus ribavirin 600-1000 mg/day or peg-IFNalpha-2a plus placebo for 48
      weeks. Additionally, peg-IFNalpha-2a plus ribavirin was administered for 48 weeks
      to 100 non-responders or relapsers (85% genotype-1) to previous interferon
      monotherapy. RESULTS: A sustained virological response (SVR) was attained among
      significantly more treatment-naive patients receiving combination therapy than
      monotherapy (61% vs 26%, P < 0.001). For patients with high baseline HCV RNA, the
      SVR rate was 59% with peg-IFNalpha-2a plus ribavirin versus 24% with peg-IFNalpha
      2a monotherapy. Among non-responders or relapsers to previous interferon
      monotherapy, 54% attained an SVR. Adverse events were generally mild, and
      discontinuations rates due to adverse events or laboratory abnormalities were
      low. CONCLUSION: In Japanese patients, peg-IFNalpha-2a plus ribavirin provided
      significant improvement in SVR rates compared with peg-IFNalpha-2a alone in
      treatment-naive patients, and was effective as re-treatment for non-responders or
      relapsers to previous treatment with interferon monotherapy.

PMID- 17444851
TI  - Single-session, graded esophageal dilation without fluoroscopy in outpatients
      with lower esophageal (Schatzki's) rings: a prospective, long-term follow-up
      study.
AB  - BACKGROUND: Distal esophageal (Schatzki's) ring is a frequent cause of dysphagia.
      Bougienage is generally effective but relapses are common. The aim of this study
      was to evaluate the safety and long-term efficacy of single-session graded
      esophageal dilation with Savary dilators, without fluoroscopic guidance, in
      outpatients who presented with Schatzki's ring. METHODS: The study was performed
      on 44 consecutive patients with symptomatic Schatzki's ring, detected
      endoscopically and/or radiologically. Graded esophageal dilation was performed as
      an outpatient procedure in a single session with Savary dilators, without
      fluoroscopic guidance. After appropriate assessment with esophageal manometry and
      24 h ambulatory pHmetry, patients with documented gastroesophageal reflux disease
      (GERD) were treated with omeprazole continuously. All results, including clinical
      follow up and technical aspects of bougienage, were recorded prospectively. The
      necessity for re-dilation after documentation of the ring with endoscopy and/or
      radiology was considered as a relapse of the ring. RESULTS: In four (9%) patients
      a second session was necessary to ensure complete symptom relief. Two (4.5%)
      patients developed post-dilation bacteremia and were managed with antibiotics as
      outpatients. Patients with (n = 14) or without (n = 30) GERD were comparable with
      respect to sex, age, body mass index, smoke and ethanol consumption, diameter of
      the esophageal lumen at the level of the ring, resting lower esophageal sphincter
      pressure, duration of dysphagia, need for taking antacids during the follow-up
      period, and duration of follow-up. There was no recurrence of the ring in
      patients with GERD during a mean follow-up period of 43.8 +/- 9.3 months (range
      27-62 months); however, in patients without GERD, during a mean follow-up period
      of 40.6 +/- 12.2 months (range 10-58 months), 32% of patients relapsed after a
      mean 19.9 +/- 10.6 months (P = 0.04). CONCLUSIONS: Single-session graded
      esophageal dilation with large caliber Savary dilators without fluoroscopic
      guidance can be safely used for the symptomatic relief in patients with lower
      esophageal (Schatzki's) rings. GERD should be treated if present in order to
      prevent a symptomatic recurrence of the ring.

PMID- 17444852
TI  - Examination of normal intestine using confocal endomicroscopy.
AB  - BACKGROUND AND AIM: Endoscopy is an important clinical tool for the diagnosis and
      treatment of gastrointestinal disorders. However, biopsy tissue is still required
      in many cases to obtain a definitive histopathological diagnosis. The aim of this
      study was to evaluate confocal endomicroscopy (CEM) as a tool for conducting
      virtual biopsies of the colon by comparing CEM images with biopsy samples from
      normal colon. METHODS: The study cohort comprised 45 patients who underwent
      investigative colonoscopy between April 2004 and January 2006, 25 of whom also
      had biopsy due to suspected diseases such as inflammation and neoplasm. The small
      and large intestine were examined with CEM using an intravenous injection of
      fluorescein, and CEM images were compared with conventional histopathological
      results from biopsied samples. In addition, the injected fluorescein was
      localized immunohistochemically to further analyze the CEM images taken in vivo.
      RESULTS: A total of 46 biopsies were taken, of which 24 demonstrated no
      histopathological abnormality and were regarded as normal. All of the CEM images
      observed from the surface to the deeper layers were concordant
      histopathologically with the biopsy results. Furthermore, CEM allowed observation
      of physiological functions such as blood flow in the capillaries of the
      surrounding crypts and mucus release from crypts. The immunohistochemical
      localization of fluorescein was consistent with the CEM images. CONCLUSIONS: CEM
      provides endoscopists with a valuable new diagnostic tool, not only for observing
      tissue in situ at the histopathological level, but also for the coincident
      evaluation of physiological function during endoscopic examination.

PMID- 17444853
TI  - The importance of metabolic factors for the increasing prevalence of fatty liver
      in Shanghai factory workers.
AB  - BACKGROUND AND AIM: To evaluate changes in the prevalence rates of
      ultrasonographic fatty liver (FL) in a specific population. METHODS: An analysis
      of the medical records of BaoSteel Group (Shanghai, China) employees was done to
      evaluate the prevalence of FL in this population, in which health examinations
      were performed biennially between 1995 and 2002. RESULTS: The study reviewed a
      database of 59 131 employees, of which 27.1% received medical check-ups four
      times within the study period, 26.6% three times, and 24.0% twice. The prevalence
      rates of obesity and metabolic disorders were high at baseline and increased
      significantly with time. The prevalence of ultrasonographic FL increased from
      3.87% to 14.04% in the overall population, while there was an increase from 4.44%
      to 14.64% in men and 1.56% to 11.37% in women over the 6-year study period.
      Increased rates of FL were also noted, from 25.88% to 51.39%, among patients with
      elevated serum alanine aminotransferase (ALT) levels (> 40 U/L). The highest
      overall prevalence rates of FL were found in individuals aged 50-60 years, with
      all age-associated prevalence significantly higher in males than females.
      CONCLUSION: The prevalence of FL increased rapidly over the study period with
      increased rates of obesity and metabolic disorders; FL is becoming a major cause
      of abnormal ALT levels in the specific population.

PMID- 17444854
TI  - Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C,
      but not hepatocellular carcinoma, and its normalization after pegylated
      interferon alfa 2a-ribavirin combination therapy.
AB  - BACKGROUND AND AIM: Elevated serum alpha-fetoprotein (AFP) levels are noted in
      patients with chronic hepatitis C (CHC) without hepatocellular carcinoma (HCC).
      The change in AFP levels after treatment with pegylated interferon and ribavirin
      (Peg-IFN/RBV) combination therapy is still unknown. The aim of this study was to
      investigate the predictors of elevated serum AFP in patients with CHC, and its
      change after Peg-IFN/RBV therapy. METHODS: A total of 123 patients, intended to
      receive pegylated interferon alfa-2a plus ribavirin therapy, were enrolled.
      Eighty-three patients had complete treatment and received follow up for and
      additional 24 weeks. The factors that may affect the elevation of pretreatment
      AFP and the normalization of post-treatment AFP were determined. RESULTS: The
      mean AFP level was 18.5 +/- 63.0 ng/mL (range, 1.3-676.0 ng/mL); 41 (33.3%) of
      the 123 patients had elevated serum AFP (more than 10 ng/mL) at baseline. A
      multivariate logistic regression analysis disclosed that older age (odds ratio
      [OR], 1.093; 95% confidence interval [CI], 1.015-1.177; P = 0.018), more advanced
      METAVIR fibrosis stage (OR, 5.237; 95% CI, 1.244-22.037; P = 0.024), a higher
      aspartate aminotransferase (AST) level (IU/L) (OR, 1.020; 95% CI, 1.008-1.033; P
      = 0.001), and lower platelet count (x10(9)/L, OR, 0.985; 95% CI, 0.968-0.994; P =
      0.003) were independent determinants of pretreatment AFP elevation. After
      treatment, 72 of 83 (86.7%) cases were found to have normal post-treatment AFP
      levels (<10 ng/mL) at the end of follow up (EOF). Post-treatment negativity of
      the chronic hepatitis C virus (HCV)-RNA (OR, 10.014; 95% CI, 1.000-100.329; P =
      0.050) and the post-treatment platelet count (x10(9)/L) (OR, 1.025; 95% CI, 1.001
      1.050; P = 0.040) were associated with normal AFP at EOF. AFP progressively
      decreased with significant differences starting from the 12th week after
      treatment to the end of treatment, and was lowest at the EOF date for the
      sustained viral response (SVR) group. On the contrary, the non-SVR group did not
      have an AFP change during and after treatment. CONCLUSION: Older age, low
      platelet count, higher AST levels, and advanced fibrosis predisposed chronic
      hepatitis C patients without HCC to have elevated serum AFP levels. After Peg
      IFN/RBV combination therapy, a higher platelet count and HCV viral eradication
      were determinants of normal AFP at EOF. Serial AFP levels decreased after
      treatment, presenting in a time-dependent manner, specifically for the SVR group.

PMID- 17444855
TI  - Hepatitis E virus infection and fulminant hepatic failure during pregnancy.
AB  - BACKGROUND AND AIM: Hepatitis E virus (HEV) infection leading to fulminant
      hepatic failure (FHF) and high mortality is a common feature in Indian women
      during the second and third trimesters of pregnancy. An altered status of
      hormones and immunity are observed during pregnancy but the actual cause of high
      mortality is still unknown. The present study was carried out to analyze CD3, CD4
      and CD8 T cell counts and to assay the level of pregnancy-related hormones such
      as estrogen, progesterone and beta-HCG in order to discover the role played by
      these factors. METHODS: One hundred patients (50 pregnant and 50 non-pregnant
      women) with FHF and 150 pregnant healthy females without liver disease as
      controls were recruited for the study. Serological tests for all viral markers
      using ELISA kits and detection of HEV RNA by reverse transcription-polymerase
      chain reaction (RT-PCR) were carried out in all cases. CD3, CD4 and CD8 T cell
      counts were analyzed by fluorescence activated cell sorter (FACS) while hormone
      assay was performed by commercially available RIA kits. RESULTS: Serologically
      (38/50; 76%) as well as by RT-PCR (28/50; 56%), a significantly higher HEV
      positivity rate was found in pregnant FHF patients compared to non-pregnant women
      (serologically 15/50; 30%; RT-PCR 7/50; 14%). CD4 counts were lower (P < 0.05),
      while CD8 counts were higher (P < 0.05), and their ratio (CD4/CD8) in HEV
      positive pregnant FHF patients was significantly lower (P < 0.01) when compared
      to that of HEV negative pregnant FHF women or controls. Levels of estrogen,
      progesterone and beta-HCG were also found to be higher (P < 0.001) in HEV
      positive pregnant FHF patients when compared to HEV negative patients or
      controls. HEV infected pregnant FHF patients had a significantly higher mortality
      rate of 65.8% (25/38) compared to 23.5% (4/15) in HEV positive non-pregnant women
      (P < 0.001). CONCLUSIONS: Pregnancy appears to be a potential risk factor for
      viral replication and an extreme low immune status of Indian/Asian pregnant
      women. It is suggested that diminished cellular immunity (indicated by a decrease
      in CD4, an increase in CD8 cell counts and lowered CD4/CD8 cell ratio) and a high
      level of steroid hormones that influence viral replication/expression during
      pregnancy appear to be the plausible reasons for severity of the disease.

PMID- 17444856
TI  - Methylation of Ras association domain family protein 1, isoform A correlated with
      proliferation and drug resistance in hepatocellular carcinoma cell line SMMC
      7721.
AB  - BACKGROUND: It has been proposed that aberrant DNA methylation can alter cancer's
      response to therapeutic agents. The purpose of the present study was to
      investigate the relationship between Ras association domain family protein 1,
      isoform A (RASSF1A) and drug resistance or growth of hepatocellular carcinoma
      cell line SMMC-7721. METHODS: Methylation status of RASSF1A from genomic gene of
      SMMC-7721 was determined with methylation-specific polymerase chain reaction and
      was further verified by demethylation treatment with 5-aza-2'-deoxycytidine. Wild
      type RASSF1A cDNA was introduced into SMMC-7721; chemosensitivity to cisplatin,
      mitomycin and fluorouracil were analyzed using 3-[4, 5-dimethylthiazol-2-yl]-2, 5
      diphenyltetrazolium bromide assay. Growth of cells was detected by colony
      formation assay and xenograft model. RESULTS: RASSF1A was inactivated in SMMC
      7721 cell line through epigenetic hypermethylation, and reintroduction of RASSF1A
      was markedly able to reduce the resistance to some anticancer drugs and inhibit
      the growth of cancer cells either in vitro or in vivo. CONCLUSION: These results
      correlate methylation status of RASSF1A with biological profiles of SMMC-7721 and
      thus, associate methylation with cancer therapy. RASSF1A may be useful to predict
      treatment response and help to develop novel treatment strategies for clinical
      treatment of hepatocellular carcinoma.

PMID- 17444857
TI  - Increased mRNA expression of chemokines in hepatocellular carcinoma with tumor
      infiltrating lymphocytes.
AB  - BACKGROUND: The infiltration of lymphocytes in tumor tissue has been associated
      with a good prognosis for patients with hepatocellular carcinoma (HCC). The
      purpose of the present study was to estimate the correlation between mRNA
      expression of chemokines and tumor-infiltrating lymphocytes in HCC. METHODS: A
      total of 44 HCC were examined. Immunohistochemical staining was performed using
      antibodies to CD4, CD8, CD68, and L-26. The mRNA expression of each chemokine was
      investigated: regulated upon activation normal T-cell expressed and secreted
      (RANTES), interleukin-8 (IL-8), epithelial-derived neutrophil attractant-78
      (ENA78), interferon-inducible protein-10 (IP-10), monokine induced by interferon
      gamma (Mig), and interferon-gamma in HCC were quantified via a real-time
      polymerase chain reaction assay. Chemokine proteins of Mig and IP-10 were
      examined by immunohistochemistry. RESULTS: The mean number of infiltrating
      lymphocytes in HCC was 136.9 +/- 32.9/0.25 mm2. Of these infiltrating
      lymphocytes, CD8-positive T lymphocytes were those predominantly seen around the
      tumor cells. The mean mRNA expression (copies/10(3) glyceraldehyde-3-phosphate
      dehydrogenase [GAPDH] mRNA) of the following chemokines was determined to be
      follows: 3.0 +/- 1.9 copies/10(3) GAPDH mRNA, RANTES; 9.2 +/- 4.9 copies/10(3)
      GAPDH mRNA, IL-8; 44.6 +/- 24.4 copies/10(3) GAPDH mRNA, ENA78; 215.7 +/- 93.9
      copies/10(3) GAPDH mRNA, IP-10; 77.3 +/- 38.5 copies/10(3) GAPDH mRNA, Mig; and
      1.7 +/- 0.4 copies/10(3) GAPDH mRNA, interferon-gamma. Significant close
      correlations were observed between the number of infiltrating lymphocytes in
      these HCC and the expression of Mig and IP-10 mRNA. In the immunostaining,
      expression of Mig and IP-10 proteins was found only in the HCC cells in the high
      infiltration group. CONCLUSIONS: Some chemokines induced by interferon-gamma,
      such as Mig and IP-10, may promote lymphocyte recruitment to HCC and may thus
      play important roles in cancer immunology.

PMID- 17444858
TI  - Oxidative-inflammatory damage in cirrhosis: effect of vitamin E and a fermented
      papaya preparation.
AB  - BACKGROUND AND AIM: Oxidative DNA damage occurs as an early event in hepatitis C
      virus (HCV) infection and is an indication of the potential for carcinogenesis.
      The aim of this study was to test a novel antioxidant/immunomodulator in patients
      with HCV-related cirrhosis. METHODS: The study group consisted of 50 patients
      with HCV-related cirrhosis with transaminase values less than twofold increased
      (alanine aminotransferase [ALT] < 80 IU/L). Patients underwent a standardized
      food-vitamin composition assessment and were assessed for dietary intake,
      nutritional status and iron level. Patients were randomly allocated into two
      groups and then given either alpha-tocopherol 900 IU/day or 9 g/day of a
      fermented papaya preparation (FPP, Immun-Age, Osato Research Institute, Gifu,
      Japan) at bedtime for 6 months. Ten healthy subjects served as controls. Patients
      were checked monthly for: routine tests, redox status (reduced glutathione,
      glutathione peroxidase, oxidized glutathione, malondialdehyde), plasma alpha
      tocopherol, 8-hydroxy-deoxy-guanidine (8-OHdG) level in circulating leukocyte DNA
      and serum levels of cytokines. RESULTS: Patients with cirrhosis showed a
      significant imbalance of redox status (low antioxidants/high oxidative stress
      markers) (P < 0.005 vs controls). Neither treatment regimen affected
      transaminases as a whole. However, vitamin E supplementation almost normalized
      ALT only in the limited vitamin-E-deficient subgroup. A significant improvement
      of redox status was obtained by both regimens. However, only FPP significantly
      decreased 8-OHdG and the improvement of cytokine balance with FPP was
      significantly better than with vitamin E treatment (P < 0.05). CONCLUSIONS:
      Although the present data seem to suggest a potential supportive role of
      antioxidants/immunomodulators as FPP in HCV patients, more studies are needed to
      substantiate their effect on the natural history of the disease.

PMID- 17444859
TI  - Methimazole protects lungs during hepatic ischemia-reperfusion injury in rats: an
      effect not induced by hypothyroidism.
AB  - BACKGROUND: Hepatic ischemia-reperfusion injury may lead to remote organ failure
      with mortal respiratory dysfunction. The aim of the present study was to analyze
      the possible protective effects of methimazole on lungs after hepatic ischemia
      reperfusion injury. METHODS: Forty male Wistar albino rats were randomized into
      five groups: a control group, in which bilateral pulmonary lobectomy was done; a
      hepatic ischemia-reperfusion group, in which bilateral pulmonary lobectomy was
      done after hepatic ischemia-reperfusion; a thyroidectomy-ischemia-reperfusion
      group (total thyroidectomy followed by, 7 days later, bilateral pulmonary
      lobectomy after hepatic ischemia-reperfusion); a methimazole-ischemia-reperfusion
      group (following methimazole administration for 7 days, bilateral pulmonary
      lobectomy was done after hepatic ischemia-reperfusion); and a methimazole +L
      thyroxine-ischemia-reperfusion group (following methimazole and L-thyroxine
      administration for 7 days, bilateral pulmonary lobectomy was performed after
      hepatic ischemia-reperfusion). Pulmonary tissue specimens were evaluated
      histopathologically and for myeloperoxidase and malondialdehyde levels. RESULTS:
      All of the ischemia-reperfusion intervention groups had higher pulmonary injury
      scoring indices than the control group (P < 0.001). Pulmonary injury index of the
      ischemia-reperfusion group was higher than that of both the methimazole
      supplemented hypothyroid and euthyroid groups (P = 0028; P = 0,038, respectively)
      and was similar to that of the thyroidectomized group. Pulmonary tissue
      myeloperoxidase and malondialdehyde levels in the ischemia-reperfusion group were
      similar with that in the thyroidectomized rats but were significantly higher than
      that in the control, and both the methimazole-supplemented hypothyroid and
      euthyroid groups. CONCLUSION: Methimazole exerts a protective role on lungs
      during hepatic ischemia-reperfusion injury, which can be attributed to its anti
      inflammatory and anti-oxidant effects rather than hypothyroidism alone.

PMID- 17444860
TI  - Age-related analysis of functional outcome and quality of life after restorative
      proctocolectomy and ileal pouch-anal anastomosis for familial adenomatous
      polyposis.
AB  - BACKGROUND: The aim of the present study was to evaluate the influence of a
      younger age at the time of ileal pouch-anal anastomosis (IPAA) on functional
      outcome and quality of life in patients with familial adenomatous polyposis
      (FAP). METHOD: A total of 105 patients with FAP who had undergone IPAA were
      retrieved from a dedicated Institutional Review Board (IRB)-approved IPAA
      database. Fifty-three patients who had complete follow-up data at 1, 3 and 5
      years were included in the study. Patients were categorized into three groups
      according to their ages at the time of surgery. Group 1, patients < or =20 years
      of age (n = 9); group 2, patients >20 and < or = 40 years of age (n = 23); and
      group 3, patients >40 years of age (n = 21). Perioperative characteristics,
      postoperative complications, quality of life scores and functional outcome at 1,
      3 and 5 years of postoperative follow-up were assessed. RESULTS: At any time
      point, there were no significant differences among the groups in terms of
      perioperative characteristics, quality of life scores or level of satisfaction
      with the procedure. However, younger patients had significantly lower nocturnal
      bowel movements at the first and third years of follow-up and tended to have less
      bowel movements per day at all stages of follow-up. CONCLUSION: These findings
      indicate that younger patients with FAP are inclined to have better functional
      outcome after IPAA in the early postoperative period. This finding may be
      encouraging for colorectal surgeons who will operate on young patients with FAP.

PMID- 17444861
TI  - Clinical usefulness of CYFRA 21-1 for esophageal squamous cell carcinoma in
      radiation therapy.
AB  - AIM: The aim of this study was to examine the clinical usefulness of cytokeratin
      19 fragments (CYFRA 21-1) compared with squamous cell carcinoma (SCC) antigen in
      patients with esophageal cancer treated with radiation therapy. METHODS: Fifty
      one patients with stage I-IV esophageal cancer were evaluated. CYFRA 21-1 and SCC
      antigen serum levels were measured at the start and the end of radiation therapy.
      RESULTS: CYFRA 21-1 (> 3.5 ng/mL) and SCC antigen (> 1.5 ng/mL) before radiation
      therapy were elevated in 63% and 53% of the patients, respectively. The CYFRA 21
      1 levels were significantly correlated with TNM stages, tumor depth and lymph
      node metastasis (P = 0.0003, P = 0.019 and P = 0.019, respectively), whereas no
      correlation was observed between SCC antigen and these factors. The values of
      CYFRA 21-1 in all patients who survived without recurrence were under the cutoff
      level at the end of treatment, but the values in all patients with locoregional
      recurrence were above the level. However, there was no significant correlation
      between SCC antigen level at the end of treatment and any clinical outcome.
      CONCLUSIONS: The results suggest that the evaluation of CYFRA 21-1 would be
      useful not only for assessment before radiation therapy but also for monitoring
      after radiation therapy in the treatment for esophageal cancer.

PMID- 17444862
TI  - Resistance rate to antibiotics of Helicobacter pylori isolates in eastern Taiwan.
AB  - BACKGROUND AND AIM: Prevalence of Helicobacter pylori (H. pylori) strains
      resistant to metronidazole, clarithromycin and amoxicillin is increasing
      worldwide. The aim of this study was to determine the antibiotic susceptibility
      patterns in H. pylori strains isolated from eastern Taiwan. METHODS: One strain
      each of H. pylori was isolated from 133 symptomatic patients and subjected to
      determination of the minimal inhibitory concentration (MIC) by the Epsilometer
      test (E-test) for four antibiotics commonly used in the treatment of H. pylori
      infections. RESULTS: None of the strains were resistant to tetracycline.
      Resistance to metronidazole (8 microg/mL), clarithromycin (1 microg/mL) and
      amoxicillin (8 microg/mL) was found in 51.9%, 13.5% and 36.1% of the isolates,
      respectively. Metronidazole-resistant strains were isolated more frequently from
      women (49/78; 62.8%) than from men (20/55; 36.4%). Resistance to at least two
      antimicrobial agents was detected in 33.8% of the isolates. There was a high rate
      of resistance to both metronidazole and amoxicillin (18.1%). CONCLUSIONS:
      Clarithromycin and tetracycline may provide useful components of treatment
      regimens in eastern Taiwan. In addition, pretreatment microbial susceptibility
      testing rather than empiric therapy is highly recommended for eradication of H.
      pylori infection.

PMID- 17444863
TI  - Clinical analysis of primary duodenal adenocarcinoma: an 11-year experience.
AB  - BACKGROUND AND AIM: The impact of obstructive jaundice (OJ) complicated by
      primary duodenal adenocarcinoma (PDA) on survival, and its treatment options, has
      rarely been mentioned in literature. The aim of the present study was to review
      the clinical features of PDA patients in an attempt to determine the prognostic
      factors and the influence of OJ on survival. METHODS: From May 1994 to February
      2005, all duodenal malignancies treated at Kaohsiung Chang Gung Memorial Hospital
      were reviewed. Preliminary findings were made on a total of 116 duodenal
      adenocarcinoma (DA) cases. After excluding metastatic DA and the papilla of Vater
      cancer, 23 patients (19.8%), confirmed as having PDA, were enrolled. RESULTS:
      Among the 23 predominantly male patients with a mean age of 68 years, abdominal
      pain was the most common symptom. Major tumor origin was the second portion, and
      the predominantly cytological feature was moderate differentiation. Tumor-node
      metastasis (TNM) cancer stage IV accounted for 47.8% of the patients, and cancer
      directed surgeries (CDS) were performed on 11 patients. Seven patients
      experienced complications due to OJ, which could be a sign of grave prognosis
      predicting survival of less than 1 year. Four of the patients received internal
      or external biliary drainage before CDS or palliative surgeries. Cigarette
      smoking, cytology, TNM stage, aspartate aminotransferase (AST), OJ, and CDS were
      significant factors of overall survival in a univariate analysis. The independent
      predictors of long-term survival were CDS, TNM stage, cytology, cigarette
      smoking, and AST using the Cox proportional hazard model. CONCLUSION: PDA
      patients who did not smoke and who were eligible for and received CDS had better
      prognostic outcomes.

PMID- 17444864
TI  - Novel interleukin-4 and interleukin-1 receptor antagonist gene variations
      associated with non-cardia gastric cancer in Japan: comprehensive analysis of 207
      polymorphisms of 11 cytokine genes.
AB  - BACKGROUND AND AIM: Helicobacter pylori (H. pylori)-induced chronic atrophic
      gastritis is a high-risk factor for gastric cancer. Immune responses to H. pylori
      are involved in gastric mucosal inflammation, and might affect clinical outcome,
      including the development of gastric cancer. The present study examines the
      significance of gene polymorphisms of various cytokines in the development of
      gastric cancer following H. pylori infection. METHODS: One hundred Japanese non
      cardia gastric cancer patients and 93 dyspeptic patients as controls were
      enrolled in the study (age range 50-75 years). All patients were positive for H.
      pylori. Genomic DNA was extracted from peripheral whole blood leukocytes, and we
      comprehensively analyzed 207 single nucleotide polymorphisms (SNP) in 11 cytokine
      genes; interleukin (IL)-1alpha, IL-1beta, IL-1 receptor antagonist (RN), IL-4, IL
      4R, IL-8, IL-10, IL-12, TNF-alpha, TNF-beta, and IFN-gamma, using either invader
      assay (163 SNP), direct sequencing (22 SNP), or PCR-restriction fragment length
      polymorphism (22 SNP). RESULTS: Among the 207 SNP examined, the IL-4 gene
      diplotypes (984 and 2983 AA/GA) had a significant negative association with
      gastric cancer development (odds ratio =0.3, 95% confidence interval =0.1-0.9).
      When we adopted the dyspeptic patients over 66 years of age as the controls, the
      IL-1RN gene diplotypes (-1102 and 6110 CG/GA) also had a significant negative
      association (odds ratio =0.2, 95% confidence interval =0.1-0.7). CONCLUSION: A
      comprehensive analysis of 207 SNP of 11 cytokine genes revealed that variations
      in IL-4 and IL-1RN genes are negatively associated with the risk of developing
      gastric cancer following H. pylori infection. Distinct host cytokine responses in
      the gastric mucosa might have a role in H. pylori-induced carcinogenesis.

PMID- 17444865
TI  - Combination therapy of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide
      and gemcitabine shows strong antitumor activity in pancreatic cancer cells.
AB  - BACKGROUND AND AIM: Poly (ADP-ribose) polymerase (PARP) inhibitors such as 3
      aminobenzamide (3-ABA) enhance the in vitro cytotoxicity of DNA mono-functional
      alkylating agents such as radiation or chemotherapeutic agents. The aim of this
      study was to test an approach combining the PARP inhibitor 3-ABA with standard
      gemcitabine therapy in human pancreatic cancer cells. METHODS: Cell viability was
      determined by proliferation assay (XTT). Cell-cycle analysis (FACS), ELISA (M30
      Apoptosense), Western blot for caspase 8 and PARP, and electron microscopy were
      used to identify apoptosis. Tumor growth and survival was assessed in nude mice
      by subcutaneously injected Capan-1 cells. In addition, Ki67 staining was
      performed on tumors for cell proliferation and in vivo apoptosis induction was
      measured by TUNEL assay and ELISA. RESULTS: Combination therapy of gemcitabine
      and 3-ABA suppressed tumor cell growth more than gemcitabine alone in XTT, FACS
      and ELISA analysis. CONCLUSION: This in vivo study demonstrated a significantly
      reduced tumor weight and increased survival up to 40 days after cell inoculation
      with combination therapy compared to animals treated with PBS, gemcitabine or 3
      ABA alone. Furthermore, TUNEL assay revealed a significant apoptosis induction
      and reduced proliferation in the combination group.

PMID- 17444866
TI  - Candida albicans aggravates duodenal ulcer perforation induced by administration
      of cysteamine in rats.
AB  - BACKGROUND: Candida sp are frequently isolated from the ascitic fluid of patients
      with perforated ulcers. The present study was performed to examine whether
      Candida infection may be involved in the process of ulcer perforation. METHODS:
      Male Wistar rats were divided into a saline group (n = 15) and a Candida group (n
      = 17). Cysteamine-HCl (Sigma; 31 mg/100 g) was administered thrice on day 1 to
      both groups of animals. Candida albicans at a density of 10(8) in 0.5 mL of
      saline was administered 1 h before, and 12 h and 24 h after the first
      administration of cysteamine in the Candida group. RESULTS: Perforated duodenal
      ulcers were observed in 94.1% of the rats in the Candida group, but only 26.7% of
      the rats in the saline group (P < 0.01). The area of the duodenal ulcers in the
      Candida group was 40.89 +/- 33.07 mm2, whereas that in the saline group was 16.53
      +/- 20.4 mm2 (P < 0.05). The mortality rate was significantly higher in the
      Candida group than in the saline group. In the Candida group, colonization by C.
      albicans was recognized at the ulcer base, surrounded by marked granulocytic
      infiltration. The number of eosinophils infiltrating the ulcer base was also
      significantly greater in the Candida group than in the saline group.
      Immunohistochemical analysis revealed the expression of secretory aspartyl
      protease (SAP) in the region of the ulcer showing colonization by C. albicans in
      the Candida group. CONCLUSION: Candida albicans aggravates duodenal ulcer
      perforation in the experimental model of cysteamine-induced duodenal ulcer
      perforation. The present findings suggest that SAP and host-parasite
      relationships, including granulocyte-dependent mechanisms, may be involved in the
      aggravation of ulcer perforation by C. albicans.

PMID- 17444867
TI  - Education and imaging. Gastrointestinal: abdominal abscess associated with a
      ventriculoperitoneal shunt.

PMID- 17444868
TI  - Education and imaging. Hepatobiliary and pancreatic: Gamna-Gandy bodies of the
      spleen.

PMID- 17444869
TI  - Education and imaging. Hepatobiliary and pancreatic: multiple hepatic adenomas.

PMID- 17444870
TI  - Education and imaging. Gastrointestinal: pneumatosis of the ascending colon.

PMID- 17444871
TI  - Education and imaging. Gastrointestinal: radiation proctitis.

PMID- 17444872
TI  - Liver injury induced by a Japanese herbal medicine, sairei-to (TJ-114, Bupleurum
      and Hoelen Combination, Chai-Ling-Tang) R1.
AB  - The case is reported of a man who showed acute hepatitis with jaundice after he
      was given a Japanese herbal medicine, sairei-to (TJ-114, Bupleurum and Hoelen
      Combination, Chai-Ling-Tang). Unusually, the component thought to be responsible
      for the observed drug-induced liver injury was able to be identified. Lymphocyte
      migration inhibition testing indicated that the tuber of the perennial herbage
      Pinellia ternate was the causative agent.

PMID- 17444873
TI  - Nosocomial Clostridium difficile infection: possible cause of anastomotic leakage
      after anterior resection of the rectum.

PMID- 17444874
TI  - Aseptic abscesses: entity already described in Crohn's disease: comment on the
      case report by Holstein et al.

PMID- 17444875
TI  - Intrafamilial transmission of hepatitis B virus infection.

PMID- 17444876
TI  - Bile duct cannulation guided by a percutaneous transhepatic biliary drainage tube
      in cases of difficult cannulation: modified rendezvous procedure.

PMID- 17444880
TI  - The origins of the developmental origins theory.
AB  - Current orthodoxy states that coronary heart disease results from the unhealthy
      lifestyles of westernized adults together with a contribution from genetic
      inheritance. This does not provide a secure basis for prevention of the disease.
      Geographical studies gave the first clue that the disease originates during intra
      uterine development. Variations in mortality from the disease across England and
      Wales were shown to correlate closely with past differences in death rates among
      newborn babies. In the past most deaths among newborns were attributed to low
      birthweight. This led to the hypothesis that undernutrition in utero permanently
      changes the body's structure, function and metabolism in ways that lead to
      coronary heart disease in later life. The association between low birthweight and
      coronary heart disease has been confirmed in longitudinal studies of men and
      women around the world. The developmental model of the origins of the disease
      offers a new way forward.

PMID- 17444881
TI  - Epidemiology, genes and the environment: lessons learned from the Helsinki Birth
      Cohort Study.
AB  - Nonoptimal growth during fetal life and infancy is associated with an increased
      risk of coronary heart disease and type 2 diabetes later in life. This early
      pattern of growth is associated with an increased disease risk especially when
      followed by a relative gain in body size later in childhood. Genetic factors are
      closely involved in growth and disease pathogenesis and gene-early life
      environmental interactions will be described affecting adult health outcomes.
      This overview will primarily focus upon findings from the Helsinki Birth Cohort
      Study consisting of 15846 subjects born 1924-1944 on whom growth data and
      information on adult health are available.

PMID- 17444882
TI  - The Uppsala studies on developmental origins of health and disease.
AB  - Large-scale epidemiological studies on developmental origins of health running in
      Uppsala benefit from the accessibility of well-archived and high quality Swedish
      records, high participation rates in the surveys, and a long tradition of
      interdisciplinary research and international collaboration. The UBCoS Multigen
      study is unique in being able to study intergenerational determinants of health
      and health inequalities as 'forward in time' processes, starting at the beginning
      of the last century, whilst the Uppsala Family and ULSAM studies contribute
      evidence on gene-environment interactions and specific mechanisms of
      developmental origins of circulatory diseases.

PMID- 17444883
TI  - Experimental IUGR and later diabetes.
AB  - It is widely accepted that an association exists between the intrauterine
      environment in which a fetus grows and develops and the subsequent development of
      type 2 diabetes. Any disturbance in maternal ability to provide nutrients and
      oxygen to the fetus can lead to fetal intrauterine growth restriction (IUGR).
      Here we will review IUGR in rodent models, in which maternal metabolism has been
      experimentally manipulated to investigate the molecular basis of the relationship
      between IUGR and development of type 2 diabetes in later life, and the
      identification of the molecular derangements in specific metabolically -
      sensitive organs/tissues.

PMID- 17444884
TI  - Programming of the stress response: a fundamental mechanism underlying the long
      term effects of the fetal environment?
AB  - There is a large body of evidence which suggests that an adverse fetal
      environment results in a heightened biobehavioral response to stress, with
      increased activity of the classical mediators of the stress response, including
      the hypothalamic-pituitary adrenal axis and autonomic nervous system. Although
      this has been amply demonstrated in animal experiments, several recent studies
      suggest that the same processes operate in human populations and may have
      important consequences for health. The evidence suggests that an adverse early
      environment or markers of an adverse environment such as low birth weight are
      linked with long-term alterations in these neuroendocrine systems. However, these
      studies also demonstrate that there is a considerable degree of heterogeneity in
      the responses observed which appear to depend on a variety of factors such as the
      nature or timing of the adverse exposure as well as the gender of the offspring.
      The mediators of these classical neuroendocrine responses such as cortisol and
      catecholamines are biologically potent and may directly influence disease
      susceptibility by means of their effects on metabolism and the vasculature.
      However, lifelong changes in the set point of these neuroendocrine systems in
      response to the early environment may also direct the course of development
      during fetal life, infancy and childhood towards the generation of a phenotype
      adapted for the adult environment predicted by the clues available during fetal
      life. This has biological advantages if the actual adult environment turns out to
      be appropriate for the phenotype. However, ill health may occur if the phenotype
      is not well matched to the actual environment encountered in adult life.

PMID- 17444885
TI  - Developmental plasticity and human disease: research directions.
AB  - The conceptual basis of the 'developmental origins' paradigm has converged on the
      role of developmental plasticity responding to signals from the early
      environment, with heightened risk of disease if the induced phenotype does not
      match the later environment. Nevertheless, numerous questions remain, including
      the current burden of disease that can be attributed to early environmental
      factors; the pathways, mechanisms and windows of plasticity; the identification
      of early markers of environmentally induced change; and the feasibility, costs
      and benefits of intervention. A focused agenda of research is needed to convince
      policy makers of the importance of developmental factors in human disease.

PMID- 17444886
TI  - Irbesartan reduces common carotid artery intima-media thickness in hypertensive
      patients when compared with atenolol: the Swedish Irbesartan Left Ventricular
      Hypertrophy Investigation versus Atenolol (SILVHIA) study.
AB  - BACKGROUND AND PURPOSE: Angiotensin II promotes cell growth and has been
      implicated in the development and maintenance of left ventricular (LV)
      hypertrophy and of structural vascular changes. We wished to examine whether an
      angiotensin receptor blocker (ARB) would influence structural vascular changes
      beyond the effects of blood pressure reduction. METHODS: Hypertensive patients
      with LV hypertrophy (age 55 +/- 9 years, blood pressure 162 +/- 19/104 +/- 8
      mmHg, LV mass index 148 +/- 31 g m(-2); mean +/- SD) were randomized double-blind
      to the ARB irbesartan (n=52) or the beta(1) receptor blocker atenolol (n=56) for
      48 weeks. Ultrasonography of the left and right common carotid artery (CCA) and
      echocardiography were performed at week 0 and 48. RESULTS: With similar
      reductions in blood pressure, CCA intima-media thickness (IMT) was reduced by
      irbesartan (from 0.92 +/- 0.14 by 0.01 +/- 0.10 mm, NS), whereas it was increased
      by atenolol (from 0.94 +/- 0.21 by 0.03 +/- 0.12 mm, P=0.018; P=0.002 between
      groups). CCA lumen diameter was less reduced by irbesartan than by atenolol.
      Thus, CCA intima-media area was reduced by irbesartan (from 21.3 +/- 5.0 by 0.90
      +/- 2.45 mm(2), P=0.034) but not by atenolol (from 21.3 +/- 6.1 by 0.18 +/- 2.71
      mm(2), NS; P=0.037 between groups). Changes in CCA IMT or area did not relate to
      changes in LV mass. CONCLUSIONS: The favourable effects by irbesartan on CCA IMT
      with an outward vascular remodelling suggest that angiotensin II mediates
      structural vascular changes, beyond the effects of blood pressure. This may be
      important in the prevention of cerebrovascular events.

PMID- 17444887
TI  - Increased catecholamines and heart rate in children with low birth weight:
      perinatal contributions to sympathoadrenal overactivity.
AB  - BACKGROUND: Low birth weight is associated with cardiovascular disease. The
      underlying mechanisms are unknown. We hypothesized that perinatal stress alters
      autonomic regulation of the cardiovascular system. In this study, catecholamines,
      heart rate (HR) and blood pressure (BP) were measured in healthy children with
      low birth weight. METHODS: This clinical study included 105 children (mean age
      9.6 years) in three groups; born at term with normal birth weight (controls,
      n=37), born at term but small for gestational age (SGA, n=29) and born preterm
      (Preterm, n=39). Dopamine, adrenaline and noradrenaline were determined in urine.
      HR and BP were measured at rest, during an orthostatic test and after a
      mathematical mental stress test. RESULTS: Children in the Preterm and SGA groups
      excreted higher levels of catecholamines when compared with controls. HR (mean
      [SD] values) were higher at rest and after mental stress in Preterm (at rest 76
      [9] and after mental stress 82 [12] min(-1)) and in SGA (79 [8] and 82 [10]) when
      compared with controls (70 [9] and 75 [9]). HR correlated with urinary
      catecholamines (r=0.24-0.27, P<0.05). Blood pressures measured at rest, during
      orthostatic testing and after mental stress did not differ between the groups.
      CONCLUSIONS: Preterm birth and fetal growth restriction are associated with
      increased sympathoadrenal activity in childhood, as indicated by stress-induced
      increases in HR and urinary catecholamines. These findings suggest that the
      cardiovascular control is differently programmed in these children with possibly
      higher risk of developing hypertension in adulthood.

PMID- 17444888
TI  - Impact of inflammation on epigenetic DNA methylation - a novel risk factor for
      cardiovascular disease?
AB  - OBJECTIVE: The lifespan of dialysis patients is as short as in patients with
      metastatic cancer disease, mainly due to cardiovascular disease (CVD). DNA
      methylation is an important cellular mechanism modulating gene expression
      associated with ageing, inflammation and atherosclerotic processes. DESIGN: DNA
      methylation was analysed in peripheral blood leucocytes from three different
      groups of chronic kidney disease (CKD) populations (37 CKD stages 3 and 4
      patients, 98 CKD stage 5 patients and 20 prevalent haemodialysis patients).
      Thirty-six healthy subjects served as controls. Clinical characteristics
      (diabetes mellitus, nutritional status and presence of clinical CVD),
      inflammation and oxidative stress biomarkers, homocysteine and global DNA
      methylation in peripheral blood leucocytes (defined as HpaII/MspI ratio by the
      Luminometric Methylation Assay method) were evaluated. CKD stage 5 patients
      (n=98) starting dialysis treatment were followed for a period of 36 +/- 2 months.
      RESULTS: Inflamed patients had lower ratios of HpaII/MspI, indicating global DNA
      hypermethylation. Analysis by the Cox regression model demonstrated that DNA
      hypermethylation (HpaII/MspI ratio <median) was significantly associated with
      both all-cause (RR 5.0; 95% CI: 1.7-14.8; P<0.01) and cardiovascular (RR 13.9;
      95% CI: 1.8-109.3; P<0.05) mortality, even following the adjustment for age, CVD,
      diabetes mellitus and inflammation. CONCLUSION: The present study demonstrates
      that global DNA hypermethylation is associated with inflammation and increased
      mortality in CKD.

PMID- 17444889
TI  - Neuromyelitis optica following CMV primo-infection.
AB  - We report the case of an acute optic neuromyelitis with rhabdomyolysis in a 34
      year-old immunocompetent transsexual patient following a recent cytomegalovirus
      (CMV) infection. The combination of optic neuropathy and myelopathy is recognized
      as Devic's syndrome. Clinical presentation was unusual as the recent CMV
      infection induced rhabdomyolysis and was the suspected trigger of neuromyelitis.

PMID- 17444890
TI  - Unique patient with cerebrotendinous xanthomatosis. Evidence for presence of a
      defect in a gene that is not identical to sterol 27-hydroxylase.
AB  - Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder
      believed to be exclusively caused by mutations in the CYP27A1 gene coding for the
      enzyme sterol 27-hydroxylase. Common findings in CTX are tendon xanthomas,
      cataracts and progressive neurological dysfunction. Here, we characterize an
      adult female patient with tendon xanthomas and classic biochemical findings of
      CTX (i.e. high levels of bile alcohols and cholestanol and extremely low levels
      of 27-hydroxycholesterol in plasma). Additionally, sterol 27-hydroxylase activity
      in cultured monocyte-derived macrophages from this patient was <5% of normal.
      Sequencing the CYP27A1 gene uncovered that the patient is heterozygous for two
      previously undescribed base substitutions in exon 8, C478A and C479A, which are
      expected to affect the haeme-binding domain of the enzyme. When expressed in
      HEK293 cells, the corresponding protein had only 8% of normal enzymatic activity.
      No other mutation was found in the open reading frame of the CYP27A1 gene, intron
      exon boundaries or in the 5'-untranslated region up to 5000 bp distal to the
      translational start site. Sequencing mRNA isolated from leucocytes from the
      patient revealed a 1 : 1 ratio of mutated and nonmutated species, with total mRNA
      levels that were not significantly different from the controls. It is concluded
      that the patient is heterozygous for two mutations affecting one allele of the
      CYP27A1 gene and with at least one additional yet undefined gene that is of
      critical importance for the activity of sterol 27-hydroxylase.

PMID- 17444891
TI  - Mechanisms of population differentiation in seabirds.
AB  - Despite recent advances in population genetic theory and empirical research, the
      extent of genetic differentiation among natural populations of animals remains
      difficult to predict. We reviewed studies of geographic variation in
      mitochondrial DNA in seabirds to test the importance of various factors in
      generating population genetic and phylogeographic structure. The extent of
      population genetic and phylogeographic structure varies extensively among
      species. Species fragmented by land or ice invariably exhibit population genetic
      structure and most also have phylogeographic structure. However, many populations
      (26 of 37) display genetic structure in the absence of land, suggesting that
      other barriers to gene flow exist. In these populations, the extent of genetic
      structure is best explained by nonbreeding distribution: almost all species with
      two or more population-specific nonbreeding areas (or seasons) have
      phylogeographic structure, and all species that are resident at or near breeding
      colonies year-round have population genetic structure. Geographic distance
      between colonies and foraging range appeared to have a weak influence on the
      extent of population genetic structure, but little evidence was found for an
      effect of colony dispersion or population bottlenecks. In two species (Galapagos
      petrel, Pterodroma phaeopygia, and Xantus's murrelet, Synthliboramphus
      hypoleucus), population genetic structure, and even phylogeographic structure,
      exist in the absence of any recognizable physical or nonphysical barrier,
      suggesting that other selective or behavioural processes such as philopatry may
      limit gene flow. Retained ancestral variation may be masking barriers to
      dispersal in some species, especially at high latitudes. Allopatric speciation
      undoubtedly occurs in this group, but reproductive isolation also appears to have
      evolved through founder-induced speciation, and there is strong evidence that
      parapatric and sympatric speciation occur. While many questions remain
      unanswered, results of the present review should aid conservation efforts by
      enabling managers to predict the extent of population differentiation in species
      that have not yet been studied using molecular markers, and, thus, enable the
      identification of management units and evolutionary significant units for
      conservation.

PMID- 17444892
TI  - Genetic diversity, but not hatching success, is jointly affected by postglacial
      colonization and isolation in the threatened frog, Rana latastei.
AB  - Both postglacial colonization and habitat fragmentation can reduce the genetic
      diversity of populations, which in turn can affect fitness. However, since these
      processes occur at different spatial and temporal scales, the consequences of
      either process may differ. To disentangle the relative role of isolation and
      postglacial colonization in determining genetic diversity and fitness, we studied
      microsatellite diversity of 295 individuals from 10 populations and measured the
      hatch rate of 218 clutches from eight populations of a threatened frog, R.
      latastei. The populations that were affected by fragmentation to a greater extent
      suffered higher embryo mortality and reduced hatch rate, while no effects of
      distance from glacial refugium on hatch rate were detected. Altogether, distance
      from glacial refugium and isolation explained > 90% of variation in genetic
      diversity. We found that the genetic diversity was lowest in populations both
      isolated and far from the glacial refugium, and that distance from refugium seems
      to have the primary role in determining genetic diversity. The relationship
      between genetic diversity and hatch rate was not significant. However, the
      proportion of genetic diversity lost through recent isolation had a significant,
      negative effect on fitness. It is possible that selection at least partially
      purged the negative effects of the ancestral loss of genetic diversity.

PMID- 17444893
TI  - Finding the relevant scale: clonality and genetic structure in a marine
      invertebrate (Crambe crambe, Porifera).
AB  - Important changes in genetic relatedness may occur at extremely small scales in
      benthic invertebrates, providing key information about structuring processes in
      populations of these organisms. We performed a small-scale study of the
      population structure of the sponge Crambe crambe, in which 177 individuals from
      the same rocky wall (interindividual distances from 0 to 7 m) were genotyped
      using six microsatellite markers. 101 sponges had unique genotypes and the
      remaining 76 individuals formed 24 groups of sponges sharing genotypes (clones).
      Mean intraclone distances were found to be c. 20 cm. Spatial autocorrelation
      analyses showed a drastic decrease in genetic relatedness over the first 100 cm
      of distance. If the contribution of clonality to this pattern was eliminated, the
      trend was attenuated, but remained a marked one and was still significant within
      the first distance classes (30-40 cm). Estimated mean dispersal distances per
      generation were c. 35 cm, and neighbourhood sizes were estimated at c. 33
      sponges. Genetic similarities with sponges of the same locality, or from other
      Mediterranean localities, were within the same range as those found in sponges 2
      7 m apart. It is concluded that asexual reproduction plays an important role in
      structuring populations in this species. However, over and above the effects of
      clonality, a strong fine-scale genetic structure was present at distances in the
      range of tens of centimetres, probably as a result of short dispersal of larvae.
      This fine-scale genetic structure may be common in invertebrates with
      lecitotrophic larvae.

PMID- 17444894
TI  - Host islands within the California Northern Channel Islands create fine-scale
      genetic structure in two sympatric species of the symbiotic ectomycorrhizal
      fungus Rhizopogon.
AB  - We have examined fine-scale genetic structure of the symbiotic ectomycorrhizal
      fungi Rhizopogon occidentalis and R. vulgaris on two of the California Channel
      Islands using five and six microsatellite loci, respectively. Both Rhizopogon
      species are sympatric on Santa Cruz and Santa Rosa Islands and are
      ectomycorrhizal with bishop pine (Pinus muricata) on both islands or Santa Rosa
      Island Torrey pine (P. torreyana ssp. insularis) on Santa Rosa. The combination
      of disjunct pine host distributions and geographic barriers within and among the
      islands have created highly structured Rhizopogon populations over very short
      distances (8.5 km on Santa Cruz Island; F(ST) = 0.258, F(ST) = 0.056, R.
      occidentalis and R. vulgaris, respectively). Both species show similar patterns
      of genetic differentiation as a result of limited dispersal between host
      populations as revealed by a significant isolation by distance relationship (r =
      0.69, P < 0.04; r = 0.93, P < 0.001, R. occidentalis and R. vulgaris,
      respectively) and Bayesian clustering analyses, and is most likely a function of
      the small foraging range of the few mammals that disperse Rhizopogon on these
      islands and the enormous spore bank characteristic of Rhizopogon species.

PMID- 17444895
TI  - Locating hybrid individuals in the red wolf (Canis rufus) experimental population
      area using a spatially targeted sampling strategy and faecal DNA genotyping.
AB  - Hybridization with coyotes (Canis latrans) continues to threaten the recovery of
      endangered red wolves (Canis rufus) in North Carolina and requires the
      development of new strategies to detect and remove coyotes and hybrids. Here, we
      combine a spatially targeted faecal collection strategy with a previously
      published reference genotype data filtering method and a genetic test for coyote
      ancestry to screen portions of the red wolf experimental population area for the
      presence of nonred wolf canids. We also test the accuracy of our maximum
      likelihood assignment test for identifying hybrid individuals using eight
      microsatellite loci instead of the original 18 loci and compare its performance
      to the Bayesian approach implemented in newhybrids. We obtained faecal DNA
      genotypes for 89 samples, 73 of which were matched to 23 known individuals. The
      performance of two sampling strategies - comprehensive sweep and opportunistic
      spot-check was evaluated. The opportunistic spot-check sampling strategy required
      less effort than the comprehensive sweep sampling strategy but identified fewer
      individuals. Six hybrids or coyotes were detected and five of these individuals
      were subsequently captured and removed from the population. The accuracy and
      power of the genetic test for coyote ancestry is decreased when using eight loci;
      however, nonred wolf canids are identified with high frequency. This combination
      of molecular and traditional field-based approaches has great potential for
      addressing the challenge of hybridization in other species and ecosystems.

PMID- 17444896
TI  - Migration between continents: geographical structure and long-distance gene flow
      in Porpidia flavicunda (lichen-forming Ascomycota).
AB  - Historical and contemporary geographical distribution ranges with their
      associated gene flow patterns interact to produce the genetic diversity observed
      today. Often it is not possible to separate out the impacts of historical events,
      e.g. past fragmentation, and contemporary gene flow, e.g. long-distance
      dispersal. Porpidia flavicunda is a lichen-forming ascomycete occurring
      circumpolar in the boreal to arctic zones for which vegetation history suggests
      that its distribution pattern has stayed broadly the same over the past
      millennia. DNA-sequence diversity in P. flavicunda can, thus, be expected to
      predominantly represent geographical population differentiation and its
      contemporary migration rates. The population sample consists of 110 specimens
      collected in Northern Quebec, Baffin Island, Western Greenland and Northern
      Scandinavia. DNA-sequence data sets of three nuclear gene fragments (LSU, RPB2
      and beta-tubulin) were analysed for genetic diversity within, and differentiation
      between, geographical regions. Tests of population subdivision employing analyses
      of molecular variance and exact tests of haplotype frequency distributions showed
      significant structure between the geographical regions. However, the lack of
      fixed nucleotide polymorphisms and the wide sharing of identical haplotypes
      between geographical regions suggest recurrent long-distance gene flow of
      propagules. Still, the means by which propagules are dispersed remain to be
      discovered. Inference of migration rates shows that in many cases a sufficiently
      high amount of migrants is exchanged between geographical regions to prevent
      drastic population differentiation through genetic drift. The observed haplotype
      distributions and migration rates point to a gene flow model of isolation by
      distance.

PMID- 17444897
TI  - Spatial analysis of nuclear and cytoplasmic DNA diversity in wild sea beet (Beta
      vulgaris ssp. maritima) populations: do marine currents shape the genetic
      structure?
AB  - Patterns of seed dispersal in the wild sea beet (Beta vulgaris ssp. maritima) are
      predicted to be influenced by marine currents because populations are widely
      distributed along the European Atlantic coast. We investigated the potential
      influence of marine currents on the pattern of spatial genetic structuring in
      natural populations of sea beet. Populations were located along the French coasts
      of the Anglo-Norman gulf that features peculiar marine currents in the Channel.
      Thirty-three populations were sampled, among which 23 were continental and 10
      were insular populations located in Jersey, Guernsey and Chausey, for a total of
      1224 plants genotyped. To validate the coastal topography influence and the
      possibility of marine current orientated gene flow on the genetic features of sea
      beet populations, we assessed patterns of genetic structuring of cytoplasmic and
      nuclear diversity by: (i) searching for an isolation-by-distance (IBD) pattern
      using spatial autocorrelation tools; (ii) using the Monmonier algorithm to
      identify genetic boundaries in the area studied; and (iii) performing assignment
      tests that are based on multilocus genotype information to ascertain population
      membership of individuals. Our results showed a highly contrasted cytoplasmic and
      nuclear genetic differentiation and highlighted the peculiar situation of island
      populations. Beyond a classical isolation-by-distance due to short-range
      dispersal, genetic barriers fitting the orientation of marine currents were
      clearly identified. This suggests the occurrence of long-distance seed dispersal
      events and an asymmetrical gene flow separating the eastern and western part of
      the Anglo-Norman gulf.

PMID- 17444898
TI  - Catchments catch all: long-term population history of a giant springtail from the
      southeast Australian highlands--a multigene approach.
AB  - Phylogeography can reveal evolutionary processes driving natural genetic
      geographical patterns in biota, providing an empirical framework for optimizing
      conservation strategies. The long-term population history of a rotting-log
      adapted giant springtail (Collembola) from montane southeast Australia was
      inferred via joint analysis of mitochondrial and multiple nuclear gene
      genealogies. Contemporary populations were identified using multilocus nuclear
      genotype clustering. Very fine-scale sampling combined with nested clade and
      coalescent-based analyses of sequences from mitochondrial cytochrome oxidase I
      and three unlinked nuclear loci uncovered marked population structure, deep
      molecular divergences, and abrupt phylogeographical breaks over distances on the
      order of tens of kilometres or less. Despite adaptations that confer low
      mobility, rare long-distance gene flow was implicated: novel computer simulations
      that jointly modelled stochasticity inherent in coalescent processes and that of
      DNA sequence evolution showed that incomplete lineage sorting alone was unable to
      explain the observed spatial-genetic patterns. Impacts of Pleistocene or earlier
      climatic cycles were detected on multiple timescales, and at least three putative
      moist forest refuges were identified. Water catchment divisions predict
      phylogeographical patterning and present-day population structure with high
      precision, and may serve as an excellent surrogate for biodiversity indication in
      sedentary arthropods from topographically heterogeneous montane temperate
      forests.

PMID- 17444899
TI  - An empirical test of freshwater vicariance via river capture.
AB  - River capture is a geomorphological process through which stream sections are
      displaced from one catchment to another, and it may represent a dominant
      facilitator of interdrainage transfer and cladogenesis in freshwater-limited
      taxa. However, few studies have been conducted in a manner to explicitly test the
      biological significance of river capture. Here we present a multispecies
      phylogeographical analysis to test whether the nonmigratory fish fauna of the Von
      River (South Island, New Zealand) is the product of a well-documented, Late
      Quaternary capture of a section of the Oreti River (Southland drainage).
      Specifically, we predict that nonmigratory fishes of the Von River will exhibit
      closer genetic affinities with those of Southland, rather than those of the
      Clutha system, into which the Von River presently drains. Mitochondrial DNA
      phylogeography (control region and cytochrome b sequence data) and analysis of
      nuclear orthologues of mtDNA sequences indicate that 'flathead'Galaxias of the
      Von River (n = 31, three sites) have greatest genetic affinities with those of
      Southland (Galaxias 'southern', n = 216, 38 sites), rather than with those of the
      Clutha River (Galaxias sp. 'D', n = 73, 32 sites). Likewise, Von River
      'roundhead'Galaxias (n = 52, four sites) have greatest genetic affinities with
      those of Southland drainages (Galaxias gollumoides, n = 223, 58 sites), rather
      than with those of the Clutha River (Galaxias pullus, Galaxias anomalus, Galaxias
      gollumoides of the Nevis tributary; n = 68, 32 sites). These findings are
      consistent with our predictions that genetic affinities of the nonmigratory fish
      fauna in the Von River would reflect past, rather than present, drainage
      connections. Consequently, river capture is responsible for the nonmigratory fish
      fauna of the Von River. In a broader context, river capture has frequently
      influenced the distribution of genetic lineages among catchments in New Zealand
      freshwater-limited fish, and its biogeographical significance may have been
      underestimated in other regions.

PMID- 17444900
TI  - Mitochondrial phylogeography of New Zealand freshwater crayfishes, Paranephrops
      spp.
AB  - Tectonic movement at the boundary of the Indo-Australian and Pacific Plates
      during the Miocene and Pliocene is recognized as a driving force for invertebrate
      speciation in New Zealand. Two endemic freshwater crayfish (koura) species,
      Paranephrops planifrons White 1842 and Paranephrops zealandicus White 1842,
      represent good model taxa to test geological hypotheses because, due to their low
      dispersal capacity and life history, geographical restriction of populations may
      be caused by vicariant processes. Analysis of a mitochondrial DNA marker
      (cytochrome oxidase subunit I) reveals not two, but three major koura lineages.
      Contrary to expectation, the cryptic West Coast group appears to be more closely
      related to P. zealandicus than to P. planifrons and has diverged earlier than the
      final development (Late Pleistocene) of Cook Strait. Our date estimates suggest
      that koura lineage diversification probably coincided with early to mid-Alpine
      orogeny in the mid-Pliocene. Estimates of node ages and the phylogenies are
      inconsistent with both ancient Oligocene and recent postglacial Pleistocene range
      expansion, but suggest central to north colonization of North Island and west to
      east movement in South Island during mid- to late Pliocene. Crypsis and paraphyly
      of the West Coast group suggest that morphological characters presently used to
      classify koura species could be misleading.

PMID- 17444901
TI  - Evolutionary history of lamprey paired species Lampetra fluviatilis (L.) and
      Lampetra planeri (Bloch) as inferred from mitochondrial DNA variation.
AB  - A remarkable trend in the evolution of lampreys is the occurrence in most genera
      of 'paired species', in which the parasitic anadromous lampreys are believed to
      have given rise to nonparasitic freshwater resident populations. The present work
      examines the phylogeography of the European paired species Lampetra fluviatilis
      and Lampetra planeri, in an attempt to elucidate species pair evolutionary
      history. We studied sequence variation in cytochrome b and ATPase 6, 8
      mitochondrial genes in 63 individuals from 21 localities of the paired species
      throughout their distribution range. Results from the phylogenetic and nested
      clade analyses were largely consistent, suggesting the existence of three major
      evolutionary lineages: lineage I and possibly lineage II are widespread
      throughout Europe, while the most ancestral lineage III is apparently restricted
      to the Iberian Peninsula. The high genetic diversity observed in the Iberian
      Peninsula is probably the result of refugial persistence and subsequent
      accumulation of variation over several ice ages, whereas the low levels of
      genetic diversity observed in central and northern Europe should reflect a rapid
      postglacial colonization. Results suggest that L. planeri originated within at
      least two distinct evolutionary lineages, rejecting the single origin hypothesis.
      The observed lack of taxa monophyly within lineage I may be the result of ongoing
      gene flow if the two taxa are alternate life-history forms of a single species.
      However, structure within lineage I is also consistent with the hypothesis of
      divergence of taxa after postglacial dispersion (around 2000 generations ago)
      with incomplete lineage sorting. Further testing of the alternative hypotheses is
      warranted.

PMID- 17444902
TI  - Host-specificity and coevolution among pollinating and nonpollinating New World
      fig wasps.
AB  - Figs (Ficus spp., Moraceae) and their pollinating wasps (Hymenoptera, Agaonidae,
      Chalcidoidea) constitute a classic example of an obligate plant-pollinator
      mutualism, and have become an ideal system for addressing questions on
      coevolution, speciation, and the maintenance of mutualisms. In addition to
      pollinating wasps, figs host several types of nonpollinating, parasitic wasps
      from a diverse array of Chalcid subfamilies with varied natural histories and
      ecological strategies (e.g. competitors, gallers, and parasitoids). Although a
      few recent studies have addressed the question of codivergence between specific
      genera of pollinating and nonpollinating fig wasps, no study has addressed the
      history of divergence of a fig wasp community comprised of multiple genera of
      wasps associated with a large number of sympatric fig hosts. Here, we conduct
      phylogenetic analyses of mitochondrial DNA sequences (COI) using 411 individuals
      from 69 pollinating and nonpollinating fig wasp species to assess relationships
      within and between five genera of fig wasps (Pegoscapus, Idarnes, Heterandrium,
      Aepocerus, Physothorax) associated with 17 species of New World Urostigma figs
      from section Americana. We show that host-switching and multiple wasp species per
      host are ubiquitous across Neotropical nonpollinating wasp genera. In spite of
      these findings, cophylogenetic analyses (TREEMAP 1.0, TREEMAP 2.02beta, and
      parafit) reveal evidence of codivergence among fig wasps from different
      ecological guilds. Our findings further challenge the classical notion of strict
      sense coevolution between figs and their associated wasps, and mirror conclusions
      from detailed molecular studies of other mutualisms that have revealed common
      patterns of diffuse coevolution and asymmetric specialization among the
      participants.

PMID- 17444903
TI  - Contemporary pollen and seed dispersal in a Prunus mahaleb population: patterns
      in distance and direction.
AB  - Pollination and seed dispersal determine the spatial pattern of gene flow in
      plant populations and, for those species relying on pollinators and frugivores as
      dispersal vectors, animal activity plays a key role in determining this spatial
      pattern. For these plant species, reported dispersal patterns are dominated by
      short-distance movements with a significant amount of immigration. However, the
      contribution of seed and pollen to the overall contemporary gene immigration is
      still poorly documented for most plant populations. In this study we investigated
      pollination and seed dispersal at two spatial scales in a local population of
      Prunus mahaleb (L.), a species pollinated by insects and dispersed by frugivorous
      vertebrates. First, we dissected the relative contribution of pollen and seed
      dispersal to gene immigration from other parts of the metapopulation. We found
      high levels of gene immigration (18.50%), due to frequent long distance seed
      dispersal events. Second, we assessed the distance and directionality for pollen
      and seed dispersal events within the local population. Pollen and seed movement
      patterns were non-random, with skewed distance distributions: pollen tended moved
      up to 548 m along an axis approaching the N-S direction, and seeds were dispersed
      up to 990 m, frequently along the SW and SE axes. Animal-mediated dispersal
      contributed significantly towards gene immigration into the local population and
      had a markedly nonrandom pattern within the local population. Our data suggest
      that animals can impose distinct spatial signatures in contemporary gene flow,
      with the potential to induce significant genetic structure at a local level.

PMID- 17444904
TI  - Utility of DNA taxonomy and barcoding for the inference of larval community
      structure in morphologically cryptic Chironomus (Diptera) species.
AB  - Biodiversity studies require species level analyses for the accurate assessment
      of community structures. However, while specialized taxonomic knowledge is only
      rarely available for routine identifications, DNA taxonomy and DNA barcoding
      could provide the taxonomic basis for ecological inferences. In this study, we
      assessed the community structure of sediment dwelling, morphologically cryptic
      Chironomus larvae in the Rhine-valley plain/Germany, comparing larval type
      classification, cytotaxonomy, DNA taxonomy and barcoding. While larval type
      classification performed poorly, cytotaxonomy and DNA-based methods yielded
      comparable results: detrended correspondence analysis and permutation analyses
      indicated that the assemblages are not randomly but competitively structured.
      However, DNA taxonomy identified an additional species that could not be resolved
      by the traditional method. We argue that DNA-based identification methods such as
      DNA barcoding can be a valuable tool to increase accuracy, objectivity and
      comparability of the taxonomic assessment in biodiversity and community ecology
      studies.

PMID- 17444905
TI  - Age-dependent genetic effects on a secondary sexual trait in male Alpine ibex,
      Capra ibex.
AB  - Secondary sexual traits, such as horns in ungulates, may be good indicators of
      genetic quality because they are costly to develop. Genetic effects on such
      traits may be revealed by examining correlations between multilocus
      heterozygosity (MLH) and trait value. Correlations between MLH and fitness
      traits, termed heterozygosity-fitness correlations (HFC), may reflect inbreeding
      depression or associative overdominance of neutral microsatellite loci with loci
      directly affecting fitness traits. We investigated HFCs for horn growth, body
      mass and faecal counts of nematode eggs in wild Alpine ibex (Capra ibex). We also
      tested if individual inbreeding coefficients (f') estimated from microsatellite
      data were more strongly correlated with fitness traits than MLH. MLH was more
      strongly associated with trait variation than f'. We found HFC for horn growth
      but not for body mass or faecal counts of nematode eggs. The effect of MLH on
      horn growth was age-specific. The slope of the correlation between MLH and yearly
      horn growth changed from negative to positive as males aged, in accordance with
      the mutation accumulation theory of the evolution of senescence. Our results
      suggest that the horns of ibex males are an honest signal of genetic quality.

PMID- 17444906
TI  - Distinct expression of endogenous Petunia vein clearing virus and the DNA
      transposon dTph1 in two Petunia hybrida lines is correlated with differences in
      histone modification and siRNA production.
AB  - Endogenous viruses exist in all kingdoms. They usually have active mechanisms of
      integration, as in bacteriophage lambda and animal retroviruses, and
      sophisticated mechanisms to maintain a proviral state over decades and
      generations. Plant para retroviruses, however, neither have an integrase, nor
      genes for maintaining the proviral state. How are those elements controlled, and
      under what conditions can they be activated? Here we study the proviral state of
      endogenous petunia vein clearing virus (ePVCV). Our results support the
      hypothesis that the proviral state is associated with a host silencing mechanism
      manifested by DNA methylation, chromatin modification and production of small
      interfering (si) RNAs. PVCV may be induced by applying abiotic stress, leading to
      the development of viral symptoms and increased transcript and siRNA levels.
      Similar levels of ePVCV DNA methylation were observed in two different lines of
      Petunia hybrida, RdC (rose du ciel) and W138, the latter known for its active
      version of transposon dTph1. In contrast, significant differences in histone
      modification were detected. The predominant association of ePVCV sequences with
      histone H3 methylated at lysine 9 (H3mK9) in RdC and with about equal amounts of
      H3mK9 and H3mK4 in W138 indicates a less repressive proviral state in the latter
      cultivar.

PMID- 17444907
TI  - Selective targeting of miRNA-regulated plant development by a viral counter
      silencing protein.
AB  - The cucumber mosaic virus (CMV) 2b protein suppresses RNA silencing and
      determines viral symptoms. Among Arabidopsis thaliana lines expressing 2b
      proteins from mild (LS and Q CMV) or severe (Fny CMV) strains, only Fny 2b
      transgenic plants displayed strong symptom-like phenotypes in leaves, stems and
      flowers, together with stunting of main root growth and increased emergence of
      lateral roots. However, LS and Fny 2b proteins both enhanced lateral root length.
      Micro (mi)RNA-mediated cellular mRNA turnover was inhibited in Fny 2b-transgenic
      plants, but there was no evidence for this in LS 2b-transgenic plants. Both 2b
      proteins efficiently suppressed small interfering (si)RNA-mediated RNA silencing,
      suggesting that 2b proteins can target the siRNA pathway without disrupting miRNA
      regulated RNA turnover. Thus, symptom induction is not an inevitable consequence
      of RNA silencing suppression. For CMV, strain-specific differences between the 2b
      silencing proteins determine whether only one or both small RNA-guided RNA
      destruction pathways are disrupted.

PMID- 17444909
TI  - Young children learning Spanish make rapid use of grammatical gender in spoken
      word recognition.
AB  - All nouns in Spanish have grammatical gender, with obligatory gender marking on
      preceding articles (e.g., la and el, the feminine and masculine forms of "the,"
      respectively). Adult native speakers of languages with grammatical gender exploit
      this cue in on-line sentence interpretation. In a study investigating the early
      development of this ability, Spanish-learning children (34-42 months) were tested
      in an eye-tracking procedure. Presented with pairs of pictures with names of
      either the same grammatical gender (la pelota, "ball [feminine]"; la galleta,
      "cookie [feminine]") or different grammatical gender (la pelota; el zapato, "shoe
      [masculine]"), they heard sentences referring to one picture (Encuentra la
      pelota, "Find the ball"). The children were faster to orient to the referent on
      different-gender trials, when the article was potentially informative, than on
      same-gender trials, when it was not, and this ability was correlated with
      productive measures of lexical and grammatical competence. Spanish-learning
      children who can speak only 500 words already use gender-marked articles in
      establishing reference, a processing advantage characteristic of native Spanish
      speaking adults.

PMID- 17444910
TI  - Picture yourself at the polls: visual perspective in mental imagery affects self
      perception and behavior.
AB  - The present research demonstrates that the visual perspective--own first-person
      versus observer's third-person--people use to picture themselves engaging in a
      potential future action affects their self-perceptions and subsequent behavior.
      On the eve of the 2004 U.S. presidential election, registered voters in Ohio were
      instructed to use either the first-person or the third-person perspective to
      picture themselves voting in the election. Picturing voting from the third-person
      perspective caused subjects to adopt a stronger pro-voting mind-set correspondent
      with the imagined behavior. Further, this effect on self-perception carried over
      to behavior, causing subjects who were instructed to picture voting from the
      third-person perspective to be significantly more likely to vote in the election.
      These findings extend previous research in autobiographical memory and social
      judgment linking the observer's perspective with dispositional attributions, and
      demonstrate the causal role of imagery in determining future behavior.

PMID- 17444911
TI  - When god sanctions killing: effect of scriptural violence on aggression.
AB  - Violent people often claim that God sanctions their actions. In two studies,
      participants read a violent passage said to come from either the Bible or an
      ancient scroll. For half the participants, the passage said that God sanctioned
      the violence. Next, participants competed with an ostensible partner on a task in
      which the winner could blast the loser with loud noise through headphones (the
      aggression measure). Study 1 involved Brigham Young University students; 99%
      believed in God and in the Bible. Study 2 involved Vrije Universiteit-Amsterdam
      students; 50% believed in God, and 27% believed in the Bible. In Study 1,
      aggression increased when the passage was from the Bible or mentioned God. In
      Study 2, aggression increased when the passage mentioned God, especially among
      participants who believed in God and in the Bible. These results suggest that
      scriptural violence sanctioned by God can increase aggression, especially in
      believers.

PMID- 17444912
TI  - Emotions and false memories: valence or arousal?
AB  - The effects of mood on false memories have not been studied systematically until
      recently. Some results seem to indicate that negative mood may reduce false
      recall and thus suggest an influence of emotional valence on false memory. The
      present research tested the effects of both valence and arousal on recall and
      recognition and indicates that the effect is actually due to arousal. In fact,
      whether participants' mood is positive, negative, or neutral, false memories are
      significantly more frequent under conditions of high arousal than under
      conditions of low arousal.

PMID- 17444913
TI  - Dissociative tendencies and memory performance on directed-forgetting tasks.
AB  - The current article presents two studies that aimed to replicate DePrince and
      Freyd's (2001, 2004) studies demonstrating that high and low dissociators
      differentially recall neutral and trauma words under conditions of varying
      cognitive load. We did not find this effect. This lack of replication was
      apparent for both free recall and word recognition memory and in both studies. In
      effect, we found little evidence to support betrayal trauma theory, yet observed
      increased memory fallibility, as demonstrated by lower general recall and (in one
      study) commission errors, in high dissociators.

PMID- 17444916
TI  - Imperceptibly off-center goalkeepers influence penalty-kick direction in soccer.

PMID- 17444917
TI  - Evaluating videotaped confessions: expertise provides no defense against the
      camera-perspective effect.

PMID- 17444918
TI  - Do narcissists dislike themselves "deep down inside"?

PMID- 17444919
TI  - Statistical reform in psychology: is anything changing?

PMID- 17444920
TI  - Required sample size to detect the mediated effect.
AB  - Mediation models are widely used, and there are many tests of the mediated
      effect. One of the most common questions that researchers have when planning
      mediation studies is, "How many subjects do I need to achieve adequate power when
      testing for mediation?" This article presents the necessary sample sizes for six
      of the most common and the most recommended tests of mediation for various
      combinations of parameters, to provide a guide for researchers when designing
      studies or applying for grants.

PMID- 17444921
TI  - The format in which uncertainty information is presented affects decision biases.
AB  - We examined how the format in which uncertainty information is presented affects
      two biases in humans' choice behavior. In a computer task, participants were
      given four common-ratio effect and four common-consequence effect problems in
      each of four different formats. In these problems, uncertainty information was
      described, as percentages (e.g., 80%) or as frequencies (e.g., 16/20), or was
      experienced, either serially (20 outcomes shown one at a time) or simultaneously
      (20 outcomes all shown at once). Presenting information as percentages attenuated
      the common-ratio effect and augmented the common-consequence effect, which
      suggests that these biases have different underlying mechanisms. Participants'
      percentage estimates of outcome likelihoods did not differ according to the
      format in which the information was presented; however, participants' nonverbal
      estimates of outcome likelihoods differed across formats. The results suggest
      that uncertainty information presented as percentages is processed differently
      than the same uncertainty information presented in other formats.

PMID- 17444922
TI  - Throwing a bomb on a person versus throwing a person on a bomb: intervention
      myopia in moral intuitions.
AB  - Most people consider it morally acceptable to redirect a trolley that is about to
      kill five people to a track where the trolley would kill only one person. In this
      situation, people seem to follow the guidelines of utilitarianism by preferring
      to minimize the number of victims. However, most people would not consider it
      moral to have a visitor in a hospital killed to save the lives of five patients
      who were otherwise going to die. We conducted two experiments in which we
      pinpointed a novel factor behind these conflicting intuitions. We show that moral
      intuitions are influenced by the locus of the intervention in the underlying
      causal model. In moral dilemmas, judgments conforming to the prescriptions of
      utilitarianism are more likely when the intervention influences the path of the
      agent of harm (e.g., the trolley) than when the intervention influences the path
      of the potential patient (i.e., victim).

PMID- 17444924
TI  - Cognitive control of sequential knowledge in 2-year-olds: evidence from an
      incidental sequence-learning and -generation task.
AB  - Under incidental instructions, thirty-eight 2-year-olds were trained on a six
      element deterministic sequence of spatial locations. Following training, subjects
      were informed of the presence of a sequence and asked to either reproduce or
      suppress the learned material. Children's production of the trained sequence was
      modulated by these instructions. When asked to suppress the trained sequence, the
      children were able to increase generation of paths that were not from the
      training sequence. Their performance was thus dependent on active suppression of
      knowledge, rather than on a random generation strategy. This degree of control in
      2-year-olds stands in stark contrast to 3-year-olds' failure to control
      explicitly instructed rule-based knowledge (as measured by the dimensional-change
      card-sort task). We suggest that the incidental nature of a learning episode
      enables the acquisition of a more procedural form of knowledge with which this
      age group has more experience prior to the onset of fluent language.

PMID- 17444923
TI  - Can infants map meaning to newly segmented words? Statistical segmentation and
      word learning.
AB  - The present experiments investigated how the process of statistically segmenting
      words from fluent speech is linked to the process of mapping meanings to words.
      Seventeen-month-old infants first participated in a statistical word segmentation
      task, which was immediately followed by an object-label-learning task. Infants
      presented with labels that were words in the fluent speech used in the
      segmentation task were able to learn the object labels. However, infants
      presented with labels consisting of novel syllable sequences (nonwords;
      Experiment 1) or familiar sequences with low internal probabilities (part-words;
      Experiment 2) did not learn the labels. Thus, prior segmentation opportunities,
      but not mere frequency of exposure, facilitated infants' learning of object
      labels. This work provides the first demonstration that exposure to word forms in
      a statistical word segmentation task facilitates subsequent word learning.

PMID- 17444925
TI  - Moral outrage mediates the dampening effect of system justification on support
      for redistributive social policies.
AB  - To understand how and why people tolerate ongoing social and economic inequality,
      we conducted two studies investigating the hypothesis that system justification
      is associated with reduced emotional distress and a lack of support for helping
      the disadvantaged. In Study 1, we found that the endorsement of a system
      justifying ideology was negatively associated with moral outrage, existential
      guilt, and support for helping the disadvantaged. In Study 2, the induction of a
      system-justification mind-set through exposure to "rags-to-riches" narratives
      decreased moral outrage, negative affect, and therefore intentions to help the
      disadvantaged. In both studies, moral outrage (outward-focused distress) was
      found to mediate the dampening effect of system justification on support for
      redistribution, whereas existential guilt (Study 1) or negative affect in general
      (Study 2; inward-focused distress) did not. Thus, system-justifying ideology
      appears to undercut the redistribution of social and economic resources by
      alleviating moral outrage.

PMID- 17444926
TI  - Heart rate variability reflects self-regulatory strength, effort, and fatigue.
AB  - Experimental research reliably demonstrates that self-regulatory deficits are a
      consequence of prior self-regulatory effort. However, in naturalistic settings,
      although people know that they are sometimes vulnerable to saying, eating, or
      doing the wrong thing, they cannot accurately gauge their capacity to self
      regulate at any given time. Because self-regulation and autonomic regulation
      colocalize in the brain, an autonomic measure, heart rate variability (HRV),
      could provide an index of self-regulatory strength and activity. During an
      experimental manipulation of self-regulation (eating carrots or cookies), HRV was
      elevated during high self-regulatory effort (eat carrots, resist cookies)
      compared with low self-regulatory effort (eat cookies, resist carrots). The
      experimental manipulation and higher HRV at baseline independently predicted
      persistence at a subsequent anagram task. HRV appears to index self-regulatory
      strength and effort, making it possible to study these phenomena in the field as
      well as the lab.

PMID- 17444927
TI  - Evaluation of mean arterial blood pressure, heart rate, and sympathetic nerve
      activity in rabbits after administration of two formulations of etomidate.
AB  - OBJECTIVE: To evaluate and compare the effects of the aqueous sulfobutyl ether
      beta-cyclodextrin (SBE-CD) etomidate formulation and the commercial etomidate
      formulation on mean arterial pressure (MAP), heart rate, and sympathetic outflow
      using neuraxis-intact and baro-denervated rabbits. STUDY DESIGN: Prospective
      experimental study. ANIMALS: Twenty-seven male New Zealand white rabbits.
      METHODS: Under basal anesthesia (urethane) and ventilation with intermittent
      positive pressure (IPPV), the New Zealand white rabbits underwent surgical
      preparation including isolation of the left renal sympathetic nerve and, in the
      baro-denervated models, additional combined denervation of bilateral carotid
      sinus, aortic, and vagal nerves. After hemodynamic stabilization, both neuraxis
      intact and baro-denervated animals received bolus intravenous (IV) injection (0.6
      mg kg(-1)) of either the SBE-CD or commercial etomidate formulation over 5
      seconds (n = 6 animals per group). RESULTS: Mean arterial pressure decreased
      significantly in all four groups to the same extent. However, the rate of MAP
      decrease was lower in the SBE-CD-treated groups relative to the commercial
      formulation. Renal sympathetic nerve activity was decreased significantly less in
      the SBE-CD group in the baro-denervated studies. Independent pharmacokinetic
      evaluation demonstrated that the two formulations had comparable plasma
      concentration-time profiles. CONCLUSIONS AND CLINICAL RELEVANCE: Etomidate in the
      commercial drug product is solubilized with propylene glycol, a cosolvent
      associated with adverse side effects on injection. An aqueous formulation of
      etomidate has been developed, which utilizes SBE-CD as a solubilizing agent. The
      data suggest that the SBE-CD etomidate formulation may be a safer IV induction
      formulation than the commercial etomidate drug product.

PMID- 17444928
TI  - Influence of the mode of ventilation on ketamine/xylazine requirements in
      rabbits.
AB  - OBJECTIVE: To evaluate the effect of the mode of mechanical ventilation (MV) on
      the dose of intravenous anesthetic during 3 hours of ketamine/xylazine
      anesthesia. STUDY DESIGN: Prospective laboratory study. ANIMALS: Sixty-one adult
      male New Zealand White rabbits. METHODS: Rabbits were anesthetized
      (ketamine/xylazine 35 + 5 mg kg(-1), IM), the trachea was intubated and
      randomized to four groups - (1) CMV-1 (n = 14), ventilated with traditional
      conventional volume-cycled MV [V(T) = 12 mL kg(-1), RR = 20, positive end
      expiratory pressure (PEEP) = 0 cmH(2)O]; (2) CMV-2 (n = 13), ventilated with a
      modern lung-protective regimen of volume-cycled MV (V(T) = 6 mL kg(-1), RR = 40,
      PEEP = 5 cmH(2)O); (3) HFPV (n = 17) ventilated with high-frequency percussive
      ventilation [high-frequency oscillations (450 minute(-1)) superimposed on 40
      minute(-1) low-frequency respiratory cycles, I:E ratio = 1:1], oscillatory
      continuous positive airway pressure (CPAP) of 7-10 cmH(2)O, and demand CPAP of 8
      10 cmH(2)O. (4) A fourth group, spontaneously ventilating (SV, n = 17), was
      anesthetized, intubated, but not ventilated mechanically. FiO(2) in all groups
      was 0.5. Anesthesia was maintained at a surgical plane by IV administration of a
      ketamine/xylazine mixture (10 + 2 mg kg(-1), as necessary) for 3 hours after
      intubation. Total dose of xylazine/ketamine administered and the need for
      yohimbine to facilitate recovery were quantitated. RESULTS: The total dose of
      xylazine/ketamine was significantly higher in the HFPV and SV groups compared
      with CMV-1 (p < 0.01). Fewer animals required yohimbine to reverse anesthesia in
      the HFPV than CMV-1 group (p < 0.05). CONCLUSIONS: The HFPV mode of MV led to
      higher doses of ketamine/xylazine being used than the other modes of MV. CLINICAL
      RELEVANCE: In rabbits, anesthetic dose for the maintenance of anesthesia varied
      with the mode of MV used. Investigators should be aware of the possibility that
      changing the mode of ventilation may lead to an alteration in the amount of drug
      required to maintain anesthesia.

PMID- 17444929
TI  - Eugenol for anesthesia of African clawed frogs (Xenopus laevis).
AB  - OBJECTIVE: To determine the level of anesthesia attained in Xenopus laevis frogs
      with eugenol at different doses and by different routes of administration. STUDY
      DESIGN: Prospective experimental trial. ANIMALS: Sixty X. laevis nonbreeding
      female frogs weighing between 90 and 140 g. METHODS: Three different routes of
      administration were tested - subcutaneous injections into the dorsal lymph sacs,
      topical administration using a gauze patch, and immersion in a bath containing
      eugenol. Following the determination of the best route of administration, the
      acetic acid test, the withdrawal reflex, righting reflex, heart rate, and
      respiratory frequency were used to evaluate central nervous system depression
      following eugenol bath administration. In an additional group, the response to a
      surgical incision of the abdominal wall was evaluated. The pharmacokinetics of
      eugenol were determined following bath immersion administration, and
      pharmacokinetic parameters were calculated following blood concentration
      determination by tandem liquid chromatography/mass spectrometry analyses.
      RESULTS: It was not possible to induce anethesia with subcutaneous and patch
      administration, independent of the eugenol dose administered. The immersion bath
      was the only efficacious route for anesthesia inducing surgical anesthesia for at
      least 30 minutes with postoperative analgesia. Histopathology of selected tissues
      (heart, lung, liver, kidneys, eyes) showed no evidence of lesions 24 hours
      following bath immersion. The elimination half-life (T(1/2)) was 4 hours.
      CONCLUSIONS: When administered as a single-bath immersion (dose 350 mg L(-1)) for
      15 minutes, eugenol may serve as an effective anesthetic in X. laevis frogs for
      short surgical procedures.

PMID- 17444930
TI  - Evaluation of an anaesthetic technique used in dogs undergoing craniectomy for
      tumour resection.
AB  - OBJECTIVE: To evaluate a total intravenous anaesthetic technique in dogs
      undergoing craniectomy. STUDY DESIGN: Prospective clinical study. ANIMALS: Ten
      dogs admitted for elective surgical resection of rostro-tentorial tumours.
      METHODS: All dogs were premedicated with methadone, 0.2 mg kg(-1) intramuscularly
      30 minutes prior to induction of anaesthesia. Anaesthesia was induced with
      propofol administered intravenously (IV) to effect, following administration of
      lidocaine 1 mg kg(-1) IV and maintained with a continuous infusion of propofol at
      < or =0.4 mg kg(-1) minute(-1) during instrumentation and preparation and during
      movement of the animals to recovery. During surgery, anaesthesia was maintained
      using a continuous infusion of propofol at <or =0.4 mg kg(-1) minute(-1) and
      alfentanil < or =1 microg kg(-1) minute(-1). Lidocaine was administered at 1 mg
      kg(-1) IV immediately prior to extubation. Arterial blood pressure and heart rate
      (HR) were recorded prior to induction and every 5 minutes throughout preparation
      and surgery. Central venous pressure was recorded every 5 minutes throughout
      surgery. RESULTS: Administration of propofol and lidocaine prevented significant
      increases in mean arterial blood pressure (MAP) and HR during endotracheal
      intubation and extubation. Adequate MAP was maintained throughout anaesthesia.
      Recovery was smooth and excitement free. There was no association between
      duration of anaesthesia, total drugs administered, or severity of neurological
      disease and recovery times. Postoperatively there was no deterioration in
      neurological function in the immediate postoperative period with complete
      resolution of pre-existing neurological deficits within 7 days of surgery.
      CONCLUSION: This technique provided minimal response to intubation and
      extubation, adequate arterial blood pressure and a smooth predictable recovery.
      All animals were neurologically improved by the time of discharge, suggesting
      that this technique had not caused significant neuronal damage. CLINICAL
      RELEVANCE: Total intravenous anaesthesia with propofol and alfentanil appears to
      be a satisfactory anaesthetic technique for use in dogs undergoing surgery for
      debulking/removal of rostro-tentorial tumours.

PMID- 17444931
TI  - Peri-operative body temperatures in isoflurane-anaesthetized rabbits following
      ketamine-midazolam or ketamine-medetomidine.
AB  - OBJECTIVE: To investigate alterations in peri-operative body temperatures and
      oesophageal-skin temperatures in isoflurane-anaesthetized rabbits following
      either ketamine-midazolam or ketamine-medetomidine induction of anaesthesia.
      ANIMAL POPULATION: Fifty client-owned rabbits, (25 male, 25 female) of different
      breeds anaesthetized for elective neutering (age range: 3-42 months; mass range:
      1.15-4.3 kg). STUDY DESIGN: Randomized, blinded clinical study. METHODS: Pre
      anaesthetic rectal temperature was measured. A 24 SWG catheter was placed in a
      marginal ear vein after local anaesthesia. Ketamine (15 mg kg(-1)) with
      medetomidine (0.25 mg kg(-1)) (group KMT) or with midazolam (3 mg kg(-1)) (group
      KMZ) was injected intramuscularly (IM). Following endotracheal intubation
      anaesthesia was maintained with isoflurane in oxygen. Carprofen (3 mg kg(-1)) and
      glucose saline (5 mL kg(-1) hour(-1)) were administered through the intravenous
      catheter. Room temperature and humidity, skin temperature (from tip of pinna) and
      oesophageal temperature were measured during anaesthesia. Ovariohysterectomy or
      castration was performed. Rectal temperature was taken when isoflurane was
      discontinued (time zero) and 30, 60 and 120 minutes thereafter. Atipamezole (0.5
      mg kg(-1)) was administered IM to rabbits in group KMT at zero plus 30 minutes.
      Mass, averaged room temperature and duration of anaesthesia data were compared
      using a two-tailed t-test. Age, averaged room humidity, rectal temperature
      decrease, oesophageal temperature decrease and oesophageal-skin difference data
      were compared using a Kruskal-Wallis test. p < 0.05 was considered significant.
      RESULTS: The averaged oesophageal-skin temperature difference was significantly
      greater in group KMT [median 9.85 degrees C (range 6.42-13.85 degrees C)] than in
      group KMZ [4.38 degrees C (2.83-10.43 degrees C)]. Rectal temperature decreased
      over the anaesthetic period was not significantly different between the two
      groups; however, oesophageal temperature decrease was significantly less in group
      KMT [1.1 degrees C (-0.1-+2.7 degrees C)] than in group KMZ [1.4 degrees C (0.6
      3.1 degrees C)]. CONCLUSIONS: Oesophageal-skin temperature difference is larger
      in rabbits anaesthetized with ketamine-medetomidine combination than ketamine
      midazolam. CLINICAL RELEVANCE: The oesophageal temperature in rabbits
      anaesthetized with ketamine-medetomidine and isoflurane decreases significantly
      less than in animals anaesthetized with ketamine-midazolam and isoflurane, during
      anaesthesia.

PMID- 17444932
TI  - An investigation of the bacterial contamination of small animal breathing systems
      during routine use.
AB  - OBJECTIVE: To investigate the need for sterilization of anaesthetic breathing
      systems to prevent cross-infection between animals due to the re-use of
      anaesthetic circuit tubing. STUDY DESIGN: Prospective microbiological study.
      METHODS: Bacteriology samples were taken from 37 sterile breathing systems, each
      used for 1 day, at two sampling sites (one proximal and one distal to the
      animal). The number of patient connections, cumulative anaesthesia time, culture
      results, number of colony-forming units and the number of different species were
      recorded. Secondly, four sterile breathing systems were used for 2 months under
      routine conditions and sampled every 2 weeks and the same parameters recorded.
      Finally, the inner surfaces of four sterile breathing systems were inoculated
      with a known load of canine oropharyngeal bacteria. Bacteriology samples were
      taken at 1 minute, 1 hour and 1 day post-deposition. The number of colonies
      identified was compared with the initial load. RESULTS: Only a very small number
      of micro-organisms were isolated and these were generally organisms of low
      pathogenic potential. The proximal site was found to be significantly more
      colonized than the distal site (p < 0.001). Neither longer daily connection time
      (p = 0.54), nor a higher number of connections (p = 0.81) increased the incidence
      of proximal site colonization. Over the 2-month study period, the bacterial
      population did not increase. There was no correlation between cultures isolated
      from successive samples taken from the same tubing. There was rapid loss of
      viability of the micro-organisms deliberately inoculated onto the tubing surface:
      the number of colonies isolated from the breathing system after 1 minute was
      significantly lower than in the inoculum (p = 0.042). CONCLUSIONS AND CLINICAL
      RELEVANCE: Sterile anaesthesia breathing systems were colonized by environmental
      micro-organisms of low pathogenicity. Although long-term survival of recognized
      pathogens in a dry environment is still possible, the use of a bacterial filter
      or a sterilized breathing system for routine veterinary anaesthesia cannot be
      supported by current evidence.

PMID- 17444933
TI  - Efficacy and cost-effectiveness of transdermal fentanyl patches for the relief of
      post-operative pain in dogs after anterior cruciate ligament and pelvic limb
      repair.
AB  - OBJECTIVES: To determine whether transdermal fentanyl patches provided cost
      effective post-operative analgesia in dogs with pelvic limb injuries. STUDY
      DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: Twenty-four
      dogs undergoing repair of ruptured cranial cruciate ligaments or pelvic limb
      fractures. METHODS: Dogs were randomly assigned to one of two groups: those
      receiving transdermal fentanyl patches (group F) and those receiving injectable
      morphine for control of post-operative pain (group M). Patients in both treatment
      groups were monitored for adequacy of analgesia and alterations in physiological
      variables. Plasma fentanyl concentrations were measured in Group F. Rescue
      morphine was given if a dog was deemed uncomfortable. The time of first rescue
      morphine, the total amount, and number of doses of morphine administered over 72
      hours was quantified and compared for each group. RESULTS: There was no
      significant treatment effect on any of the parameters, except for serum cortisol
      concentration, which was significantly lower overall in group F (p = 0.01). Pain
      scores peaked at 6 hours post-extubation and were higher than baseline from 2 to
      20 hours post-extubation. Cortisol concentrations were the highest at time 0
      (extubation) and were significantly higher than baseline until 2 hours post
      extubation. Pain scores correlated with fentanyl plasma concentrations (p =
      0.0001 and p = 0.01, respectively), but the correlation was low (r = 0.26 and r =
      0.16, respectively). No correlation was found between serum cortisol
      concentrations and pain scores in either group. Fentanyl cost and total cost for
      pain management were considerably higher for group F. CONCLUSIONS: Fentanyl
      patches did not provide better analgesia or a reduced requirement for rescue
      opioid compared with intramuscular morphine. CLINICAL RELEVANCE: When considering
      overall costs to the client for comparable analgesic intervention, fentanyl
      patches increased rather than decreased cost during the first 24 hours post
      operatively.

PMID- 17444934
TI  - Characteristics of the relationship between plasma ketamine concentration and its
      effect on the minimum alveolar concentration of isoflurane in dogs.
AB  - OBJECTIVE: To characterize the shape of the relationship between plasma ketamine
      concentration and minimum alveolar concentration (MAC) of isoflurane in dogs.
      STUDY DESIGN: Retrospective analysis of previous data. ANIMALS: Four healthy
      adult dogs. METHODS: The MAC of isoflurane was determined at five to six
      different plasma ketamine concentrations. Arterial blood samples were collected
      at the time of MAC determination for measurement of plasma ketamine
      concentration. Plasma concentration/effect data from each dog were fitted to a
      sigmoid inhibitory maximum effect model in which MAC(c)= MAC(0) - (MAC(0)
      MAC(min)) x C(gamma)/EC(50)(gamma)+C(gamma), where C is the plasma ketamine
      concentration, MAC(c) is the MAC of isoflurane at plasma ketamine concentration
      C, MAC(0) is the MAC of isoflurane without ketamine, MAC(min) is the lowest MAC
      predicted during ketamine administration, EC(50) is the plasma ketamine
      concentration producing 50% of the maximal MAC reduction, and gamma is a
      sigmoidicity factor. Nonlinear regression was used to estimate MAC(min), EC(50),
      and gamma. RESULTS: Mean +/- SEM MAC(min), EC(50) and gamma were estimated to be
      0.11 +/- 0.01%, 2945 +/- 710 ng mL(-1) and 3.01 +/- 0.84, respectively. Mean +/-
      SEM maximal MAC reduction predicted by the model was 92.20 +/- 1.05%.
      CONCLUSIONS: The relationship between plasma ketamine concentration and its
      effect on isoflurane MAC has a classical sigmoid shape. Maximal MAC reduction
      predicted by the model is less than 100%, implying that high plasma ketamine
      concentrations may not totally abolish gross purposeful movement in response to
      noxious stimulation in the absence of inhalant anesthetics. CLINICAL RELEVANCE:
      The parameter estimates reported in this study will allow clinicians to predict
      the expected isoflurane MAC reduction from various plasma ketamine concentrations
      in an average dog.

PMID- 17444935
TI  - Traumatic endotracheal intubation in the cat.
AB  - BACKGROUND: Orotracheal intubation is a commonly performed procedure in the cat,
      but it is not without complications. Tracheal rupture has been reported in cats,
      but trauma to the arytenoids from intubation has not been documented.
      OBSERVATIONS: An otherwise healthy, 5-year-old male domestic shorthair cat
      presented for total ear canal ablation to resolve intractable otitis media and
      externa. The cat was premedicated with glycopyrrolate, hydromorphone, and
      acepromazine. Anesthesia was induced with diazepam and ketamine, and maintained
      with isoflurane in oxygen. During orotracheal intubation, the larynx was poorly
      visualized and excessive force was used to perform intubation. Subsequently,
      blood was observed in the larynx and laryngoscopy revealed a tear lateral to the
      patient's right arytenoid which had been created during intubation. The larynx
      was re-intubated normally and the cat suffered no obvious ill effects from the
      trauma to the larynx. CONCLUSIONS: Direct observation and proper technique must
      be employed during orotracheal intubation in cats in an attempt to avoid
      laryngeal trauma.

PMID- 17444936
TI  - Suspected air embolism associated with post-anesthetic pulmonary edema and
      neurologic sequelae in a horse.
AB  - A 523 kg Quarter Horse was anesthetized for unilateral eye enucleation. The
      anesthetic period was unremarkable. During anesthetic recovery the cap on the
      jugular venous catheter became dislodged. Clinical signs of pulmonary edema
      associated with moderate arterial hypoxemia subsequently developed. Although
      pulmonary edema resolved with medical therapy, the day following anesthetic
      recovery, clinical signs of vestibular disease and blindness developed. Treatment
      included nasal oxygen insufflation, flunixin meglumine, furosemide,
      dexamethasone, thiamine, dimethylsulfoxide, antimicrobials, and phenylbutazone.
      The horse recovered and was discharged from the hospital after 7 days of
      treatment and was neurologically normal at 6 weeks. While venous air embolism was
      not confirmed in this case, the catheter cap complication followed by signs of
      pulmonary edema and neurologic sequelae support the presumptive pathogenesis of
      this horse's complications. Diagnostic confirmation of air embolism in horses
      with compatible acute clinical signs should be documented with echocardiography.

PMID- 17444939
TI  - Monitoring of neuronal and glial calcium activity using a novel direct-contact
      probe.
AB  - In vivo neuronal and glial calcium activity was monitored using a novel direct
      contact probe that was designed for fluorescence detection deep within biological
      tissue. A small diameter fibre bundle direct-contact probe was employed with a
      laser scanning confocal microscope to detect evoked neuronal and glial activity
      in the posteromedial barrel subfield of the rat somatosensory cortex in vivo.
      Resolution of the probe allowed discrimination of single cells, and calcium
      dynamics spanning milliseconds to several seconds were observed. Initial results
      indicate that the probe has useful practical applications in the imaging of
      individual cells and monitoring rapid calcium fluctuations within their cell body
      and large processes.

PMID- 17444940
TI  - Fluorescence lifetime imaging microscopy of Chlamydomonas reinhardtii: non
      photochemical quenching mutants and the effect of photosynthetic inhibitors on
      the slow chlorophyll fluorescence transient.
AB  - Fluorescence lifetime-resolved images of chlorophyll fluorescence were acquired
      at the maximum P-level and during the slower transient (up to 250 s, including P
      S-M-T) in the green photosynthetic alga Chlamydomonas reinhardtii. At the P
      level, wild type and the violaxanthin-accumulating mutant npq1 show similar
      fluorescence intensity and fluorescence lifetime-resolved images. The zeaxanthin
      accumulating mutant npq2 displays reduced fluorescence intensity at the P-level
      (about 25-35% less) and corresponding lifetime-resolved frequency domain phase
      and modulation values compared to wild type/npq1. A two-component analysis of
      possible lifetime compositions shows that the reduction of the fluorescence
      intensity can be interpreted as an increase in the fraction of a short lifetime
      component. This supports the important photoprotection function of zeaxanthin in
      photosynthetic samples, and is consistent with the notion of a 'dimmer switch'.
      Similar, but quantitatively different, behaviour was observed in the intensity
      and fluorescence lifetime-resolved imaging measurements for cells that were
      treated with the electron transport inhibitor 3-(3,4-dichlorophenyl)-1,1-dimethyl
      urea, the efficient PSI electron acceptor methyl viologen and the protonophore
      nigericin and. Lower fluorescence intensities and lifetimes were observed for all
      npq2 mutant samples at the P-level and during the slow fluorescence transient,
      compared to wild type and the npq1 mutant. The fluorescence lifetime-resolved
      measurements during the slow fluorescence changes after the P level up to 250 s
      for the wild type and the two mutants, in the presence and absence of the above
      inhibitors, were analyzed with a graphical procedure (polar plots) to determine
      lifetime compositions. At higher illumination intensity, wild type and npq1 cells
      show a rise in fluorescence intensity and corresponding rise in the species
      concentration of the slow lifetime component after the initial decrease following
      the P level. This reversal is absent in the npq2 mutant, and for all samples in
      the presence of the inhibitors. Lifetime heterogeneities were observed in
      experiments averaged over multiple cells as well as within single cells, and
      these were followed over time. Cells in the resting state (induced by several
      hours of darkness), instead of the normal swimming state, show shortened
      lifetimes. The above results are discussed in terms of a superposition of effects
      on electron transfer and protonation rates, on the so-called 'State Transitions',
      and on non-photochemical quenching. Our data indicate two major populations of
      chlorophyll a molecules, defined by two 'lifetime pools' centred on slower and
      faster fluorescence lifetimes.

PMID- 17444941
TI  - An automated feedback system with the hybrid model of scoring and classification
      for solving over-segmentation problems in RNAi high content screening.
AB  - BACKGROUND: High content screening (HCS) via automated fluorescence microscopy is
      a powerful technology for generating cellular images that are rich in phenotypic
      information. RNA interference is a revolutionary approach for silencing gene
      expression and has become an important method for studying genes through RNA
      interference-induced cellular phenotype analysis. The convergence of the two
      technologies has led to large-scale, image-based studies of cellular phenotypes
      under systematic perturbations of RNA interference. However, existing high
      content screening image analysis tools are inadequate to extract content
      regarding cell morphology from the complex images, thus they limit the potential
      of genome-wide RNA interference high content screening screening for simple
      marker readouts. In particular, over-segmentation is one of the persistent
      problems of cell segmentation; this paper describes a new method to alleviate
      this problem. METHODS: To solve the issue of over-segmentation, we propose a
      novel feedback system with a hybrid model for automated cell segmentation of
      images from high content screening. A Hybrid learning model is developed based on
      three scoring models to capture specific characteristics of over-segmented cells.
      Dead nuclei are also removed through a statistical model. RESULTS: Experimental
      validation showed that the proposed method had 93.7% sensitivity and 94.23%
      specificity. When applied to a set of images of F-actin-stained Drosophila cells,
      91.3% of over-segmented cells were detected and only 2.8% were under-segmented.
      CONCLUSIONS: The proposed feedback system significantly reduces over-segmentation
      of cell bodies caused by over-segmented nuclei, dead nuclei, and dividing cells.
      This system can be used in the automated analysis system of high content
      screening images.

PMID- 17444942
TI  - Scanning probe microscopies applied to the study of the domain wall in a
      ferroelectric crystal.
AB  - Scanning near-field optical microscopy is capable of measuring the topography and
      optical signals at the same time. This fact makes this technique a valuable tool
      in the study of materials at nanometric scale and, in particular, of
      ferroelectric materials, as it permits the study of their domains structure
      without the need of chemical etching and, therefore, not damaging the surface (as
      will be demonstrated later). We have measured the scanning near-field optical
      microscopy transmission, as well as the topography, of an RbTiOPO(4) single
      crystalline slab, which exhibits two different of macroscopic ferroelectric
      domains. A chemical selective etching has been performed to distinguish between
      them, obtaining areas with a noticeable roughness (C(-) domain) in comparison
      with the original flat aspect of the other ones (C(+) domain). The effects of the
      selective chemical etching have been quantified in topographic images obtained by
      means of our fibre tip probe, and have been compared to topographic images
      obtained by Atomic Force Microscopy, with a better resolution. The near-field
      optical transmission images recorded have been obtained under different
      excitation wavelengths. These images are modulated by the light scattering due to
      the grains at the rough surface, which depends on the excitation wavelength used.
      In addition, they show a significant optical contrast due to the variations of
      the dielectric constant on the proximity of the ferroelectric domain wall.

PMID- 17444943
TI  - Method for determination of the displacement field in patterned nanostructures by
      TEM/CBED analysis of split high-order Laue zone line profiles.
AB  - A method to extract accurate information on the displacement field distribution
      from split high-order Laue zones lines in a convergent-beam electron diffraction
      pattern of nanostructures has been developed. Starting from two-dimensional many
      beam dynamical simulation of HOLZ patterns, we assembled a recursive procedure to
      reconstruct the displacement field in the investigated regions of the sample,
      based on the best fit of a parametrized model. This recursive procedure minimizes
      the differences between simulated and experimental patterns, taken in strained
      regions, by comparing the corresponding rocking curves of a number of high-order
      Laue zone reflections. Due to its sensitivity to small displacement variations
      along the electron beam direction, this method is able to discriminate between
      different models, and can be also used to map a strain field component in the
      specimen. We tested this method in a series of experimental convergent-beam
      electron diffraction patterns, taken in a shallow trench isolation structure. The
      method presented here is of general validity and, in principle, it can be applied
      to any sample where not negligible strain gradients along the beam direction are
      present.

PMID- 17444944
TI  - Multiscale image analysis of microcellular solids: application to hybrid silica
      xerogels.
AB  - A general methodology is proposed to characterize microcellular solids, the
      structure of which consists of a three-dimensional network of filamentary
      structures. The analysis is based on transmission electron microscopy observation
      of the filaments individually and of their spatial arrangement. The micrographs
      are analyzed with grey-tone digital image analysis techniques, such as opening
      granulometry and correlation analysis. The methodology is applied to hybrid
      organic-inorganic low-density silica solids synthesized by the sol-gel method
      with an organically modified co-reactant. The quantitative impact of the co
      reactant on each structural level of the structure is assessed quantitatively.

PMID- 17444945
TI  - Precision of light intensity measurement in biological optical microscopy.
AB  - Standardization and calibration of optical microscopy systems have become an
      important issue owing to the increasing role of biological imaging in high
      content screening technology. The proper interpretation of data from high-content
      screening imaging experiments requires detailed information about the
      capabilities of the systems, including their available dynamic range, sensitivity
      and noise. Currently available techniques for calibration and standardization of
      digital microscopes commonly used in cell biology laboratories provide an
      estimation of stability and measurement precision (noise) of an imaging system at
      a single level of signal intensity. In addition, only the total noise level, not
      its characteristics (spectrum), is measured. We propose a novel technique for
      estimation of temporal variability of signal and noise in microscopic imaging.
      The method requires registration of a time series of images of any stationary
      biological specimen. The subsequent analysis involves a multi-step process, which
      separates monotonic, periodic and random components of every pixel intensity
      change in time. The technique allows simultaneous determination of dark, photonic
      and multiplicative components of noise present in biological measurements.
      Consequently, a respective confidence interval (noise level) is obtained for each
      level of signal. The technique is validated using test sets of biological images
      with known signal and noise characteristics. The method is also applied to assess
      uncertainty of measurement obtained with two CCD cameras in a wide-field
      microscope.

PMID- 17444946
TI  - High-resolution compact X-ray microscopy.
AB  - We demonstrate compact full-field soft X-ray transmission microscopy with sub 60
      nm resolution operating at lambda= 2.48 nm. The microscope is based on a 100-Hz
      regenerative liquid-nitrogen-jet laser-plasma source in combination with a
      condenser zone plate and a micro-zone plate objective for high-resolution imaging
      onto a 2048 x 2048 pixel CCD detector. The sample holder is mounted in a helium
      atmosphere and allows imaging of both dry and wet specimens. The microscope
      design enables fast sample switching and the sample can be pre-aligned using a
      visible-light microscope. High-quality images can be acquired with exposure times
      of less than 5 min. We demonstrate the performance of the microscope using both
      dry and wet samples.

PMID- 17444947
TI  - Rapid freeze-substitution preserves membranes in high-pressure frozen tissue
      culture cells.
AB  - We describe a method for high-pressure freezing and rapid freeze-substitution of
      cells in tissue culture which provides excellent preservation of membrane detail
      with negligible ice segregation artefacts. Cells grown on sapphire discs were
      placed 'face to face' without removal of tissue culture medium and frozen without
      the protection of aluminium planchettes. This reduction in thermal load of the
      sample/holder combination resulted in freezing of cells without visible ice
      crystal artefact. Freeze-substitution at -90 degrees C for 60 min in acetone
      containing 2% uranyl acetate, followed by warming to -50 degrees C and embedding
      in Lowicryl HM20 gave consistent and clear membrane detail even when imaged
      without section contrasting. Preliminary data indicates that the high intrinsic
      contrast of samples prepared in this way will be valuable for tomographic
      studies. Immunolabelling sensitivity of sections of samples prepared by this
      rapid substitution technique was poor; however, reducing the uranyl acetate
      concentration in the substitution medium to 0.2% resulted in improved labelling.
      Samples substituted in this lower concentration of uranyl acetate also gave good
      membrane detail when imaged after section contrasting.

PMID- 17444949
TI  - Mechanisms of hypoxic signal transduction regulated by reactive nitrogen species.
AB  - Recent reports devoted to the field of oxygen sensing outline that signalling
      molecules such as nitric oxide/nitric oxide derived species as well as cytokines
      and other inflammatory mediators participate in hypoxic signal transduction. In
      the present review, we summarize the current knowledge about the role of nitric
      oxide and reactive nitrogen species (RNS) derived from it in hypoxic signal
      transduction and particularly in accumulation/de-accumulation of hypoxia
      inducible factor 1 alpha (HIF-1alpha) protein, which is critical not only for
      cellular adaptation to low oxygen availability but also for generation of
      inflammatory and innate immune responses. After brief description of nitric oxide
      and other RNS as multifunctional messengers we analyse and discuss the RNS
      dependent accumulation of HIF-1alpha protein under normoxia followed by
      discussion of the mechanisms of nitric oxide (NO)-dependent enzyme-regulated
      degradation of HIF-1alpha protein under low oxygen availability.

PMID- 17444950
TI  - Treatment with anti-TNF alpha does not induce reactivation of latent Salmonella
      enterica serovar Typhimurium infection in C3H/HeN mice.
AB  - Therapy with tumour necrosis factor-alpha (TNFalpha)-blocking agents is
      successful in treating inflammatory disorders, but carries an increased risk of
      manifest and reactivating infection with intracellular bacteria. In a mouse model
      of latent Salmonella typhimurium infection, neutralization of TNFalpha did not
      result in reactivation of infection, suggesting only a minor role for TNFalpha
      during latency of persistent Salmonella infection.

PMID- 17444951
TI  - Passive transfer of experimental autoimmune neuritis by IL-12 and IL-18
      synergistically potentiated lymphoid cells is regulated by NKR-P1+ cells.
AB  - The aim of this study was to investigate the roles and mechanism of interleukin
      12 (IL-12) and interleukin-18 (IL-18) in potentiating the autoreactivity of
      lymphoid cells specific for P2 53-78 peptide. P2 53-78-specific lymphoid cells in
      the presence of IL-12 or IL-18 alone passive transferred only moderate
      experimental autoimmune neuritis (EAN) into a low percentage of recipients.
      However, lymphoid cells co-cultured with both cytokines transferred aggressive
      clinical and histological EAN into all recipients. NKR-P1+ cells (including NK
      and NKT cells) played an immunosuppressive function in passive transfer EAN and
      depletion of NKR-P1+ cells by anti-NKR-P1 Ab and complement induced a more
      serious form of EAN. Nevertheless, lymphoid cells co-cultured with both IL-12 and
      IL-18 induced high levels of interferon-gamma (IFN-gamma) and promoted Th1
      differentiation partially through NKR-P1+ cells and to some extent, NKR-P1+ cell
      depletion inhibited the auto-reactivity of lymphoid cells treated with IL-12 and
      IL-18.

PMID- 17444952
TI  - Dextran sulfate sodium-induced colitis generates a transient thymic involution-
      impact on thymocyte subsets.
AB  - One of the most widely used animal models for inflammatory bowel disease (IBD) is
      the dextran sulfate sodium (DSS)-induced colitis. We have previously reported
      that 5 days administration of DSS in C57Bl/6J mice induces a colonic inflammation
      that progresses into chronicity after DSS removal, whereas in BALB/cJ mice the
      inflammation resolves within 4 weeks post-DSS. Here we show that both thymic size
      and thymocyte numbers dramatically decreased in the acute phase of inflammation
      in C57Bl/6 mice, 7 days after DSS withdrawal. Mature, CD4(+) and CD8(+) single
      positive (SP) CD69(lo) CD62L(hi) thymocytes were enriched in these mice,
      accompanied by a major decrease in the number of immature double positive (DP)
      thymocytes. However, the different maturation stages within the DP thymocyte
      subset were unchanged between healthy and inflamed C57Bl/6J mice. Interestingly,
      as the inflammation progressed into the chronic phase, the thymus recovered and 2
      weeks after the acute inflammatory phase all the thymic parameters investigated
      in this study were restored to normal. In contrast, BALB/cJ mice only develop
      mild thymic alterations. Nevertheless, we found that within the double negative
      (DN) thymocytes an increased frequency and also total numbers of CD44(+) CD25(-)
      (DN1) cells correlated with the severity of colitis, and that the frequency of
      CD44(-) CD25(-) (DN4) thymocytes decreased proportionally in the acute phase in
      BALB/cJ mice. Our observations suggest that the thymic effects are intimately
      connected to the intestinal inflammatory response in colitis regardless of the
      inflammatory stimuli.

PMID- 17444953
TI  - A novel mannose-binding lectin-associated serine protease 1/3 gene variant.
AB  - The ficolins and mannose-binding lectin (MBL) create complexes with three
      different serine proteases (MASP-1, MASP-2 and MASP-3) and a truncated non
      enzymatic form of MASP-2 (sMAP). MASP-2 is able to activate complement by
      cleavage of C4 and C2, while the physiological functions of MASP-1, MASP-3 and
      sMAP still are debated. MASP-1 and MASP-3 are alternative spliced forms of the
      same MASP gene. To gain insight in the molecular variation in the MASP-1/3 gene,
      we undertook a systematic study of the protein coding sequences of the MASP-1/3
      gene. The coding regions of the MASP-1/3 gene were sequenced in 92 healthy
      Caucasian donors. A total of six nucleotide substitutions were detected. Five
      were detected only once. One polymorphism identified in exon 10 at position
      +50074 (rs 38343199) relative to the transcription start site resulting in the
      amino acid substitution of a glycine (GGG) with a glutamic acid residue (GAG) in
      the second complement control protein domain was observed. The frequency of this
      allele in 305 blood donors, 90 patients with systemic lupus erythematosus and 234
      patients with the systemic inflammatory response syndrome (SIRS) and/or sepsis
      was 0.03, 0.017 and 0.03 respectively. No significant differences in genotype
      frequencies between the groups were observed (P > 0.45). However, the SIRS/sepsis
      group deviated from the Hardy-Weinberg expectations due to one variant allele
      homozygote (P = 0.07), which was not observed in the other groups. In conclusion,
      the MASP1/3 gene harbours a low-frequent polymorphic site resulting in an amino
      acid substitution, which may influence the function of the gene product.

PMID- 17444954
TI  - Epitope mapping of series of monoclonal antibodies against the hepatocellular
      carcinoma-associated antigen HAb18G/CD147.
AB  - The hepatocellular carcinoma-associated antigen HAb18G/CD147, a member of CD147
      family, could promote tumour invasion and metastasis via inducing the secretion
      of matrix metalloproteinases (MMP). Anti-CD147 monoclonal antibodies (MoAb) have
      exhibited obvious inhibitory effect on MMP induction. However, none of the
      epitopes of these MoAb has been reported. We previously prepared five MoAb
      against HAb18G/CD147, named HAb18, 3B3, 1B3, 5A5 and 4D2. To map the epitopes of
      these MoAb, a series of truncated fragments of extracellular region of
      HAb18G/CD147 was expressed in Escherichia coli and the MoAb-binding affinity to
      these fragments was examined with an enzyme-linked immunosorbent assay and
      Western blot. The residues (39)LTCSLNDSATEV(50), (36)KILLTCS(42) and
      (22)AAGTVFTTVEDL(33) were determined to be the epitopes of HAb18, 3B3 and 1B3,
      respectively, which were further proved by a dot-blot analysis with synthesized
      peptides and bioinformatics epitope prediction. The binding regions of MoAb 5A5
      and 4D2 were located at residues E(120)-R(203). Then we constructed and expressed
      full-length HAb18G/CD147 and truncated HAb18G/CD147 without residues A(22)-V(50)
      in COS-7 cells. Gelatin zymography and Boyden chamber assay showed that the COS-7
      cells expressing truncated HAb18G/CD147 failed to induce MMP production and
      enhance the cells' invasive potential, compared with the cells expressing full
      length HAb18G/CD147. Taken together with the obviously inhibitory effects of
      HAb18 on the function of full-length HAb18G/CD147, these findings suggest that
      residues (22)AAGTVFTTVEDLGSKILLTCSLNDSATEV(50) may play a critical role in the
      functions of HAb18G/CD147 on MMP secretion and tumour invasion. These key
      residues can be used as potential drug target in cancer therapy.

PMID- 17444955
TI  - The influence of MHC class II molecules containing the rheumatoid arthritis
      shared epitope on the immune response to aggrecan G1 and its peptides.
AB  - Aggrecan has been implied as an autoantigen in rheumatoid arthritis (RA).
      Immunization with aggrecan induces arthritis in BALB/c (H-2(d)) mice but not in
      other strains of mice [e.g. C57BL/6 (H-2(b))]. In humans, the strongest genetic
      association with RA is to the shared epitope (SE), and aggrecan peptides are
      predicted to bind to the SE. Therefore, we hypothesized that C57BL/6 mice
      transgenic (tg) for the RA SE (DR4 tg mice) may be susceptible to aggrecan
      induced arthritis. C57BL/6 and DR4 tg mice were immunized with a mixture of SE
      binding aggrecan peptides and tested for immune responses to the corresponding
      peptides as well as aggrecan. Sustained T- and B-cell immune responses to
      aggrecan and several of its peptides were detected in DR4 tg mice. C57BL/6 mice
      showed only transient T-cell responses to different immunizing peptides and
      little B-cell response. Therefore, an immune response to peptides of aggrecan can
      be induced experimentally in DR4 tg mice as anticipated from the predicted and
      actual binding affinities of these peptides for the RA SE. Failure to induce
      arthritis in these DR4 tg mice may be due to a lack of appropriate non-MHC genes.

PMID- 17444956
TI  - Osteopontin, a protein with cytokine-like properties, is associated with
      inflammation in Crohn's disease.
AB  - In Crohn's disease (CD) mucosal T-cells produce increased interferon-gamma (IFN
      gamma) and tumour necrosis factor-alpha (TNF-alpha) levels and TNF-alpha antibody
      treatment [Infliximab (Ifx)] is effective. Osteopontin (OPN), a glycoprotein
      stimulating activated T-lymphocytes, may be involved in the disturbed immune
      regulation but also in normal immune-homeostasis and mucosal repair, since it is
      expressed in many tissues and present in human milk. This study investigates
      plasma-OPN levels in CD patients during Ifx treatment and the in vitro effect of
      OPN on intestinal T cells. Thirty-seven CD patients received three Ifx doses at
      week 0, 2 and 6. Blood samples, colonic biopsies and clinical scores were
      obtained before treatment and at week 8, 26 and 52. In-vivo activated T-cell
      cultures were established from colonic biopsies in the presence of interleukin
      (IL)-2 and IL-4. The in vitro effect of OPN stimulation on T-cell IFN-gamma, TNF
      alpha, and IL-10 production was measured. Plasma-OPN was increased in active CD
      (increased CRP-level) compared with quiescent disease (P = 0.02) and declined
      after three Ifx doses (P = 0.04). It was inversely correlated with in vitro T
      cell IL-10 production. OPN increased CD69 and CD25 expression and enhanced T-cell
      IFN-gamma and TNF-alpha production in a dose-dependent fashion with higher levels
      in CD than in healthy controls (HC), but induced a concomitant higher IL-10
      production in HC than CD. In conclusion, plasma-OPN levels are related to CD
      inflammation. In vitro, OPN-stimulated IL-10 production increases less in T-cell
      cultures from CD patients than from HC, indicating that IL-10 deficiency may be
      involved in the defect immune-regulation in CD, even after OPN stimulation.

PMID- 17444957
TI  - The expression of BAFF-binding receptors is not altered in multiple sclerosis or
      myasthenia gravis.
AB  - Multiple sclerosis (MS) is a chronic, progressive disease of the central nervous
      system (CNS) characterized by consistent myelin injury. Antibody-mediated death
      of oligodendrocytes is a pathological feature in a subset of MS patients and may
      be of relevance to disease pathogenesis. In myasthenia gravis (MG), acetylcholine
      receptors (AChR) situated at the neuromuscular endplate are destroyed by
      autoreactive antibodies. B-cell activating factor of the tumour necrosis factor
      (TNF) superfamily (BAFF) is essential for B-cell survival. Using flow cytometry,
      we evaluated the expression of three BAFF-binding receptors, namely, BAFF
      receptor (BAFF-R), B-cell maturation antigen (BCMA), and transmembrane activator
      and calcium modulating and cyclophilin ligand interactor (TACI) in peripheral
      blood lymphocytes. Nearly all CD19(+) B cells and CD19(+)CD27(+) memory B cells
      expressed BAFF-R. The intensity of BAFF-R expression was not statistically
      different in MS or MG compared with healthy controls. Very few T cells expressed
      BAFF-R. BCMA expression was strictly limited to B cells. Although both B and T
      cells expressed TACI, levels were much higher on B cells compared with levels on
      T cells. The percentages of B and T cells expressing BCMA and TACI did not differ
      significantly in MS or MG versus controls. We conclude that the expression of
      BAFF-binding receptors is not appreciably altered in MS or MG.

PMID- 17444958
TI  - MHC class II tetramer guided detection of Mycobacterium tuberculosis-specific
      CD4+ T cells in peripheral blood from patients with pulmonary tuberculosis.
AB  - Novel diagnostic tools are needed to diagnose latent infection and to provide
      biologically meaningful surrogate markers to define cellular immune responses
      against Mycobacterium tuberculosis (MTB). Interferon gamma-based assays have
      recently been developed in addition to the more than 100-year-old tuberculin skin
      test (TST) for the immune diagnosis of MTB in blood. The advent of soluble
      MHC/peptide tetramer molecules allows to objectively enumerate antigen-specific T
      cells. We identified novel MHC class II-restricted MTB epitopes and used HLA-DR4
      tetrameric complexes to visualize ex vivo CD4(+) T cells directed against the
      antigens Ag85B and the 19-kDa lipoprotein, shared between MTB and other
      Mycobacterium species, and CD4(+) T cells which recognize the MTB-associated ESAT
      6 antigen. MTB-reactive CD4(+) T cells reside predominantly in the CD45RA(+)
      CD28(+) and CD45(-) CD28(+) T-cell subset and recognize naturally processed and
      presented MTB epitopes. HLA-DR4-restricted, Ag85B or ESAT-6-specific CD4(+) T
      cells show similar dynamics over time in peripheral blood mononuclear cells
      (PBMC) when compared with CD8(+) T cells directed against the corresponding HLA
      A2-presented MTB epitopes in patients with pulmonary MTB infection and subsequent
      successful therapy. This was not found to be true for T-cell responses directed
      against the 19-kDa lipoprotein. The dissection of the cellular immune response in
      M. tuberculosis infection will enable novel strategies for monitoring MTB vaccine
      candidates and to gauge CD4(+) T cells directed against MTB.

PMID- 17444959
TI  - An agonist antibody specific for CD40 induces dendritic cell maturation and
      promotes autologous anti-tumour T-cell responses in an in vitro mixed autologous
      tumour cell/lymph node cell model.
AB  - CD40-mediated interactions play an important role in the response to a variety of
      diseases, including cancer. Engagement of CD40 on antigen-presenting cells,
      namely dendritic cells (DC), by CD40L leads to maturation and up-regulation of co
      stimulatory molecules B7.1 and B7.2 (CD80 and CD86). These molecules are
      requisite to subsequent antigen-specific activation of T cells. T-cell activation
      is a critical aspect of specific anti-tumour immune responses that have become
      the focus of a variety of cancer immunotherapy approaches. Clinical trials
      involving immunologic interventions have shown clinical responses confirming that
      the immune system can be harnessed for the treatment of cancer. However, the
      clinical response rate has been low, signifying the need for new
      immunotherapeutic strategies. To this end, an agonist antibody specific for CD40,
      CP-870,893, has been developed. A fully autologous mixed tumour cell/lymph node
      cell model was utilized to demonstrate that CP-870,893 promotes the
      responsiveness of lymph node-derived T cells to autologous tumour. Specifically,
      T cells from the tumour-draining lymph nodes are not responsive to autologous
      tumour cells; however, in the presence of CP-870,893, this unresponsiveness is
      reversed, as indicated by lymph node cell proliferation and cytokine secretion.
      Monocyte-derived DC treated with CP-870,893 consistently display a mature
      phenotype: up-regulation of CD80, CD83, CD86 and HLA-DR expression, increased
      Mip1alpha and IL-12 secretion, and the loss of exogenous antigen-presenting
      capability subsequent to treatment with the antibody. These data indicate that CP
      870,893 binds to and activates DC, ultimately driving a specific anti-tumour T
      cell response.

PMID- 17444960
TI  - Prevalence of obesity in Denmark.
AB  - There has been a pronounced, distinctive increase of the prevalence of obesity
      within almost all age groups of the Danish population, during the last 25-30
      years. The largest increase has been documented in studies based on objective
      data from total populations and the latest data show the increase will continue.
      The Danish studies show heterogeneity in the development of the obesity epidemic.
      A close association with birth cohorts indicates a need for further aetiological
      research, not only into behavioural factors, but also into early life factors
      that may explain some of this developmental pattern.

PMID- 17444961
TI  - The burden of overweight and obesity in the Asia-Pacific region.
AB  - The rise in the prevalence of overweight and obesity (body mass index >or=25 kg
      m(-2)) is, in part, a negative consequence of the increasing economic
      developments of many lower- and middle-income countries in the Asia-Pacific
      region. To date, there has been no systematic quantification of the scale of the
      problem in countries of this region. From the most recent nationally
      representative estimates for the prevalence of overweight and obesity in 14
      countries of the region, it is apparent that overweight and obesity is endemic in
      much of the region, prevalence ranging from less than 5% in India to 60% in
      Australia. Moreover, although the prevalence in China is a third of that in
      Australia, the increase in prevalence in China over the last 20 years was 400%
      compared with 20% in Australia. In addition, across various countries in the
      region, the population attributable fractions because of overweight and obesity
      ranged from 0.8% to 9.2% for coronary heart disease mortality, 0.2% to 2.9% for
      haemorrhagic stroke mortality, and 0.9% to 10.2% for ischaemic stroke mortality.
      These results indicate that consequences of overweight and obesity for health and
      the economy of many of these countries are likely to increase in coming years.

PMID- 17444962
TI  - Measurement of television viewing in children and adolescents: a systematic
      review.
AB  - The relationship between television (TV) viewing and overweight in children is
      likely to be influenced by the quality of measures used. We systematically
      reviewed studies related to overweight in children that had included a measure of
      TV exposure. Literature searches were conducted in MedLINE, PsychInfo,
      SportDiscus and ISIWeb of Science. Methods of assessing TV viewing were
      evaluated, including the type of measure, the administration procedure and
      reported psychometric properties. The majority of studies assessed TV viewing
      using self-report surveys and very few studies used direct observation. The
      validity or reliability of measures was often not examined. The majority of tools
      that were evaluated were compared with another self-report measure or an
      objective measure of physical activity. TV viewing measures should be selected
      that are specific to the research question, the study design, as well as
      methodological feasibility. However, it is recommended that measures of TV
      viewing be used only if they have psychometric data to support their validity and
      reliability. Selecting measures that are valid and reliable enables us to examine
      with greater accuracy the influence of TV viewing on childhood overweight, as
      well as the efficacy of interventions designed to reduce TV viewing in children.

PMID- 17444963
TI  - Fasting - the ultimate diet?
AB  - Adult humans often undertake acute fasts for cosmetic, religious or medical
      reasons. For example, an estimated 14% of US adults have reported using fasting
      as a means to control body weight and this approach has long been advocated as an
      intermittent treatment for gross refractory obesity. There are unique historical
      data sets on extreme forms of food restriction that give insight into the
      consequences of starvation or semi-starvation in previously healthy, but usually
      non-obese subjects. These include documented medical reports on victims of hunger
      strike, famine and prisoners of war. Such data provide a detailed account on how
      the body adapts to prolonged starvation. It has previously been shown that
      fasting for the biblical period of 40 days and 40 nights is well within the
      overall physiological capabilities of a healthy adult. However, the specific
      effects on the human body and mind are less clearly documented, either in the
      short term (hours) or in the longer term (days). This review asks the following
      three questions, pertinent to any weight-loss therapy, (i) how effective is the
      regime in achieving weight loss, (ii) what impact does it have on psychology? and
      finally, (iii) does it work long-term?

PMID- 17444964
TI  - The prevalence and determinants of obesity in adults with intellectual
      disabilities.
AB  - People with intellectual disabilities experience significant health inequalities
      compared with the general population, including a shorter life expectancy and
      high levels of unmet health needs. Another accepted measure of health
      inequalities, the prevalence of obesity, has been shown to be higher in adults
      with intellectual disabilities than in the general population. While the factors
      contributing to the increased prevalence among adults with intellectual
      disabilities are not well understood, the high rates of obesity among younger
      adults highlight the need for further research involving children and adolescents
      with intellectual disabilities. To take forward the priorities for research and
      the development of effective, accessible services, there is a need for
      collaboration between professionals working in the fields of intellectual
      disabilities and obesity.

PMID- 17444965
TI  - Animal and human tissue Na,K-ATPase in normal and insulin-resistant states:
      regulation, behaviour and interpretative hypothesis on NEFA effects.
AB  - The sodium(Na)- and potassium(K)-activated adenosine-triphosphatase (Na,K-ATPase)
      is a membrane enzyme that energizes the Na-pump by hydrolysing adenosine
      triphosphate and wasting energy as heat, so playing a role in thermogenesis and
      energy balance. Na,K-ATPase regulation by insulin is controversial; in tissue of
      hyperglycemic-hyperinsulinemic ob/ob mice, we reported a reduction, whereas in
      streptozotocin-treated hypoinsulinemic-diabetic Swiss and ob/ob mice we found an
      increased activity, which is against a genetic defect and suggests a regulation
      by hyperinsulinemia. In human adipose tissue from obese patients, Na,K-ATPase
      activity was reduced and negatively correlated with body mass index, oral glucose
      tolerance test-insulinemic area and blood pressure. We hypothesized that obesity
      is associated with tissue Na,K-ATPase reduction, apparently linked to
      hyperinsulinemia, which may repress or inactivate the enzyme, thus opposing
      thyroid hormones and influencing thermogenesis and obesity development. Insulin
      action on Na,K-ATPase, in vivo, might be mediated by the high level of non
      esterified fatty acids, which are circulating enzyme inhibitors and increase in
      obesity, diabetes and hypertension. In this paper, we analyse animal and human
      tissue Na,K-ATPase, its level, and its regulation and behaviour in some
      hyperinsulinemic and insulin-resistant states; moreover, we discuss the link of
      the enzyme with non-esterified fatty acids and attempt to interpret and organize
      in a coherent view the whole body of the exhaustive literature on this
      complicated topic.

PMID- 17444966
TI  - Epicardial fat: properties, function and relationship to obesity.
AB  - Epicardial fat is a relatively neglected component of the heart. The purpose of
      this review was to examine the anatomic and biochemical data on epicardial fat;
      to examine the relationship of epicardial fat to obesity and to explore the
      potential role of epicardial fat in the relationship of obesity to coronary
      atherothrombotic disease. Epicardial fat covers 80% of the heart's surface and
      constitutes 20% of total heart weight. It is present along the distribution of
      the coronary arteries, over the right ventricle especially along the right
      border, anterior surface and at the apex. There is three- to fourfold more
      epicardial fat associated with the right than the left ventricle. Putative
      physiologic functions of epicardial fat are based on observational data and
      include: buffering coronary arteries against the torsion induced by the arterial
      pulse wave and cardiac contraction, facilitating coronary artery remodelling,
      regulating fatty acid homeostasis in the coronary microcirculation and providing
      fatty acids to cardiac muscle as a local energy source in times of high demand. A
      considerable amount of the data on epicardial fat originates from autopsy series
      that have the inherent problem that conditions leading to death may have altered
      body composition and adiposity. With this caveat, data indicate that epicardial
      fat mass increases age until age 20-40 years but thereafter the amount of
      epicardial fat is not dependent on age. The amount of epicardial fat correlates
      with heart weight but the presence of myocardial ischemia and hypertrophy does
      not alter the ratio of epicardial fat to cardiac muscle mass. A number of
      properties differentiate epicardial fat from other fat depots specifically its
      smaller adipocytes size; different fatty acid composition, high protein content;
      high rates of fatty acid incorporation, fatty acid synthesis, insulin-induced
      lipogenesis or fatty acid breakdown; low rates of glucose utilization, low
      expression (mRNA) of lipoprotein lipase, stearoyl-CoA desaturase and acetyl-CoA
      carboxylase-alpha, and slow regression during weight loss. There is a significant
      direct relationship between the amount of epicardial fat and general body
      adiposity. Clinical imaging studies have demonstrated a strong direct correlation
      between epicardial fat and abdominal visceral adiposity. Several lines of
      evidence support a role for epicardial fat in the pathogenesis of coronary artery
      disease, namely the close anatomic relationship between epicardial fat and
      coronary arteries; the positive correlation between the amount of epicardial fat
      and the presence of coronary atherosclerosis and the ability of adipose tissue to
      secrete hormones and cytokines that modulate coronary artery atherothrombosis.
      Thus, epicardial fat maybe an important factor responsible for cardiovascular
      disease in obesity.

PMID- 17444967
TI  - The Collaborative Study of Obesity and Diabetes in Adults (CODA) project: meta
      analysis design and description of participating studies.
AB  - The Collaborative Study of Obesity and Diabetes in Adults (CODA) project was
      formed to establish an international database of studies of abdominal obesity and
      type 2 diabetes mellitus (T2DM), and to provide analyses of these associations
      using individual participant data (IPD) meta-analytic techniques. The
      collaboration involves obtaining raw data from existing studies. The main
      objectives of the collaboration are to assess which simple anthropometric indices
      most closely predict the risk of T2DM in adults, and to investigate ethnicity and
      other factors that potentially modify that prediction. A second task related to
      primary prevention of diabetes subsequently evolved, the CODA-2 project, and is
      concerned with population-based methods to identify people most likely to benefit
      from diabetes interventions. This article describes the meta-analysis design and
      the studies involved. The collaboration currently has 37 studies enrolled,
      providing data on 260,000 participants. The proposed IPD meta-analyses will help
      resolve several outstanding issues in diabetes.

PMID- 17444968
TI  - Paul Pierre Broca (1824-1880).

PMID- 17444969
TI  - Bayesian networks, Bayesian learning and cognitive development.

PMID- 17444970
TI  - Sensitivity to sampling in Bayesian word learning.
AB  - We report a new study testing our proposal that word learning may be best
      explained as an approximate form of Bayesian inference (Xu & Tenenbaum, in
      press). Children are capable of learning word meanings across a wide range of
      communicative contexts. In different contexts, learners may encounter different
      sampling processes generating the examples of word-object pairings they observe.
      An ideal Bayesian word learner could take into account these differences in the
      sampling process and adjust his/her inferences about word meaning accordingly. We
      tested how children and adults learned words for novel object kinds in two
      sampling contexts, in which the objects to be labeled were sampled either by a
      knowledgeable teacher or by the learners themselves. Both adults and children
      generalized more conservatively in the former context; that is, they restricted
      the label to just those objects most similar to the labeled examples when the
      exemplars were chosen by a knowledgeable teacher, but not when chosen by the
      learners themselves. We discuss how this result follows naturally from a Bayesian
      analysis, but not from other statistical approaches such as associative word
      learning models.

PMID- 17444971
TI  - Bayes nets and babies: infants' developing statistical reasoning abilities and
      their representation of causal knowledge.
AB  - A fundamental assumption of the causal graphical model framework is the Markov
      assumption, which posits that learners can discriminate between two events that
      are dependent because of a direct causal relation between them and two events
      that are independent conditional on the value of another event(s). Sobel and
      Kirkham (2006) demonstrated that 8-month-old infants registered conditional
      independence information among a sequence of events; infants responded according
      to the Markov assumption in such a way that was inconsistent with models that
      rely on simple calculations of associative strength. The present experiment
      extends these findings to younger infants, and demonstrates that such responses
      potentially develop during the second half of the first year of life. These data
      are discussed in terms of a developmental trajectory between associative
      mechanisms and causal graphical models as representations of infants' causal and
      statistical learning.

PMID- 17444972
TI  - Learning overhypotheses with hierarchical Bayesian models.
AB  - Inductive learning is impossible without overhypotheses, or constraints on the
      hypotheses considered by the learner. Some of these overhypotheses must be
      innate, but we suggest that hierarchical Bayesian models can help to explain how
      the rest are acquired. To illustrate this claim, we develop models that acquire
      two kinds of overhypotheses--overhypotheses about feature variability (e.g. the
      shape bias in word learning) and overhypotheses about the grouping of categories
      into ontological kinds like objects and substances.

PMID- 17444973
TI  - Preschool children learn about causal structure from conditional interventions.
AB  - The conditional intervention principle is a formal principle that relates
      patterns of interventions and outcomes to causal structure. It is a central
      assumption of experimental design and the causal Bayes net formalism. Two studies
      suggest that preschoolers can use the conditional intervention principle to
      distinguish causal chains, common cause and interactive causal structures even in
      the absence of differential spatiotemporal cues and specific mechanism knowledge.
      Children were also able to use knowledge of causal structure to predict the
      patterns of evidence that would result from interventions. A third study suggests
      that children's spontaneous play can generate evidence that would support such
      accurate causal learning.

PMID- 17444974
TI  - Using domain-general principles to explain children's causal reasoning abilities.
AB  - A connectionist model of causal attribution is presented, emphasizing the use of
      domain-general principles of processing and learning previously employed in
      models of semantic cognition. The model categorizes objects dependent upon their
      observed 'causal properties' and is capable of making several types of inferences
      that 4-year-old children have been shown to be capable of. The model gives rise
      to approximate conformity to normative models of causal inference and gives
      approximate estimates of the probability that an object presented in an ambiguous
      situation actually possesses a particular causal power, based on background
      knowledge and recent observations. It accounts for data from three sets of
      experimental studies of the causal inferencing abilities of young children. The
      model provides a base for further efforts to delineate the intuitive mechanisms
      of causal inference employed by children and adults, without appealing to
      inherent principles or mechanisms specialized for causal as opposed to other
      forms of reasoning.

PMID- 17444975
TI  - The Bayesian revolution approaches psychological development.
AB  - This commentary reviews five articles that apply Bayesian ideas to psychological
      development, some with psychology experiments, some with computational modeling,
      and some with both experiments and modeling. The reviewed work extends the
      current Bayesian revolution into tasks often studied in children, such as causal
      learning and word learning, and provides evidence that children's performance can
      be optimal in a Bayesian sense. There remains much to be done in terms of
      understanding how representations are created, how development occurs, how
      Bayesian computation might be neurally implemented, and in reconciling the new
      work with older evidence that even skilled adults are incompetent Bayesians.

PMID- 17444976
TI  - On the relation between the acquisition of singular-plural morpho-syntax and the
      conceptual distinction between one and more than one.
AB  - We investigated the relationship between the acquisition of singular-plural
      morpho-syntax and children's representation of the distinction between singular
      and plural sets. Experiment 1 tested 18-month-olds using the manual-search
      paradigm and found that, like 14-month-olds (Feigenson & Carey, 2005), they
      distinguished three objects from one but not four objects from one. Thus, they
      failed to represent four objects as 'plural' or 'more than one'. Experiment 2
      found that children continued to fail at the 1 vs. 4 manual-search task at 20
      months of age, even when told, via explicit morpho-syntactic singular-plural
      cues, that one or many balls are being hidden. However, 22- and 24-month-olds
      succeeded both with and without verbal cues. Parental report data indicated that
      most 22- and 24-month-olds, but few 20-month-olds, had begun producing plural
      nouns in their speech. Also, the success among the older children was due to
      those children who had reportedly begun producing plural nouns. We discuss a
      possible role for language acquisition in children's deployment of set-based
      quantification and the distinction between singular and plural sets.

PMID- 17444977
TI  - Story contexts increase susceptibility to the DRM illusion in 5-year-olds.
AB  - False recognition in children aged 5, 8, and 11 years was investigated using the
      standard version of the Deese-Roediger-McDermott (DRM) procedure and an
      alternative version in which the DRM stimuli were embedded in stories designed to
      emphasize their overall theme. Relative to the 8- and 11-year-olds, the 5-year
      olds falsely recognized fewer critical lures when the DRM stimuli were presented
      in lists, but falsely recognized more critical lures when the stimuli were
      presented in stories. Levels of false recognition in the 8- and 11-year-olds were
      not affected by study format. We argue that the story context enhanced the
      ability of the 5-year-olds to make inferences based on the theme of the DRM
      stimuli. The 5-year-olds then showed higher levels of false recognition than the
      older children owing to their inability to reject lure words consistent with the
      stories.

PMID- 17444978
TI  - Infants' perception of goal-directed actions: development through cue-based
      bootstrapping.
AB  - It is now widely accepted that sensitivity to goal-directed actions emerges
      during the first year of life. However, controversy still surrounds the question
      of how this sensitivity emerges and develops. One set of views emphasizes the
      role of observing behavioral cues, while another emphasizes the role of
      experience with producing own action. In a series of four experiments we contrast
      these two views. In Experiment 1, it was shown that infants as young as 6 months
      old can interpret an unfamiliar human action as goal-directed when the action
      involves equifinal variations. Experiments 2 and 3 demonstrated that 12- and 9
      month-olds are also able to attribute goals to an inanimate action if it displays
      behavioral cues such as self-propelledness and an action-effect. In Experiment 4,
      we found that even 6-months-olds can encode the goal object of an inanimate
      action if all three cues, equifinality, self-propelledness and an action-effect,
      were present. These findings suggest that the ability to ascribe goal
      directedness does not necessarily emerge from hands-on experience with particular
      actions and that it is independent from the specific appearance of the actor as
      long as sufficient behavioral cues are available. We propose a cue-based
      bootstrapping model in which an initial sensitivity to behavioral cues leads to
      learning about further cues. The further cues in turn inform about different
      kinds of goal-directed agents and about different types of actions. By uniting an
      innate base with a learning process, cue-based bootstrapping can help reconcile
      divergent views on the emergence of infants' ability to understand actions as
      goal-directed.

PMID- 17444979
TI  - Perception of object shape and texture in human newborns: evidence from cross
      modal transfer tasks.
AB  - The present research investigates newborn infants' perceptions of the shape and
      texture of objects through studies of the bi-directionality of cross-modal
      transfer between vision and touch. Using an intersensory procedure, four
      experiments were performed in newborns to study their ability to transfer shape
      and texture information from vision to touch and from touch to vision. The
      results showed that cross-modal transfer of shape is not bi-directional at birth.
      Newborns visually recognized a shape previously held but they failed to tactually
      recognize a shape previously seen. In contrast, a bi-directional cross-modal
      transfer of texture was observed. Taken together, the results suggest that
      newborn infants, like older children and adults, gather information differently
      in the visual and tactile modes, for different object properties. The findings
      provide evidence for continuity in the development of mechanisms for perceiving
      object properties.

PMID- 17444980
TI  - Gravity bias in young and adult chimpanzees (Pan troglodytes): tests with a
      modified opaque-tubes task.
AB  - Young human children at around 2 years of age fail to predict the correct
      location of an object when it is dropped from the top of an S-shape opaque tube.
      They search in the location just below the releasing point (Hood, 1995). This
      type of error, called a 'gravity bias', has recently been reported in dogs and
      monkeys. In the present study, we investigated whether young and adult
      chimpanzees also show such a gravity bias in a modified version of the original
      opaque-tube task. The original task by Hood and colleagues required the subject
      to search in a location after the object had fallen, while in the task reported
      here, subjects were required to predict the location before the object was
      dropped. Thus the present procedure does not involve explicit invisible
      displacement operations, one of the important components of the original
      procedure. In Experiment 1 both young (1.5-2.5-year-old) and adult chimpanzees
      predicted the location of falling food items below the releasing point even when
      crossed tubes were used. These gravity errors remained after the extensive
      experience of using the tubes themselves. Experiment 2 further tested adult and 4
      year-old chimpanzees under the set-up in which the straight and crossed tubes
      were simultaneously presented. The results were the same as those in the previous
      test, suggesting that developmental changes and learning effect do not affect the
      gravity bias in chimpanzees.

PMID- 17444981
TI  - Guest editorial: social work theory, research, policy and practice - challenges
      and opportunities in health and social care integration in the UK.

PMID- 17444982
TI  - Globalisation, rural restructuring and health service delivery in Australia:
      policy failure and the role of social work?
AB  - The impacts of globalisation and rural restructuring on health service delivery
      in rural Australia have been significant. In the present paper, it is argued that
      declining health service access represents a failure of policy. Rural communities
      across the world are in a state of flux, and Australia is no different: rural
      communities are ageing at faster rates than urban communities and young people
      are out-migrating in large numbers. During the past 5 years, rural Australia has
      also experienced a severe and widespread drought that has exacerbated rural
      poverty, and impacted on the health and well-being of rural Australians.
      Australian governments have responded to globalising forces by introducing
      neoliberal policy initiatives favouring market solutions and championing the need
      for self-reliance among citizens. The result for rural Australia has been a
      withdrawal of services at a time of increased need. This paper addresses the
      social work response to these changes.

PMID- 17444983
TI  - Factors affecting participation in Sure Start programmes: a qualitative
      investigation of parents' views.
AB  - The objectives of the present study were to examine the factors that parents
      identify as promoting or hindering participation in Sure Start programmes, and to
      identify methods for enhancing parents' engagement with Sure Start. A
      qualitative, in-depth interview study was conducted with parents registered with
      two local Sure Start programmes based in the East Midlands, UK, and located in
      inner city areas with a range of health and social problems associated with
      social exclusion and disadvantage. Sixty parents, guardians or carers of children
      living in both Sure Start areas were recruited during autumn of 2004 on the basis
      of whether they were identified as a 'frequent user' or 'non-frequent user' of
      Sure Start services. The data were analysed using a thematic approach supported
      by NVivo computer software, and explanatory themes were subsequently tested for
      completeness and adequacy. The results of the study indicated that parents who
      used Sure Start services were positive about the benefits that they obtained for
      themselves and their children, in particular in overcoming a sense of isolation.
      Parents who were non-frequent users identified a number of practical reasons that
      prevented them using Sure Start services, although parents also recognised a loss
      of confidence and trust in the local communities summarised in the phrase
      'keeping myself to myself'. Parents' awareness of the targeted nature of Sure
      Start can also lead to stigma and reluctance to use services. It is concluded
      that continued investment of time and effort in maintaining communication
      networks between Sure Start staff and local parents is vital if parents and
      children are to make the best use of Sure Start services.

PMID- 17444984
TI  - Fear of loss of independence and nursing home admission in older Australians.
AB  - A prerequisite for the success of any health or social care policy is the ability
      to address the concerns of the target group. The findings described in the
      present paper form part of a larger study of the hopes and fears that older
      people hold for their future. Data were collected through a cross-sectional,
      population-based telephone interview survey conducted in New South Wales,
      Australia, from 1999 to 2000. The participants (n = 8881) were randomly selected,
      community-dwelling older people (>/= 65 years). Survey weights were used for
      estimating proportions and for all statistical inferences. The prevalence of
      expressing fears for the future was estimated, and analyses of selected
      predictors of specific fears for self were conducted by logistic regression
      modelling, with males and females modelled separately. The present paper focuses
      on two of the reported fears for self: loss of independence and nursing home
      admission, which have implications for healthcare and service use; and the
      authors identify the extent of their association with sociodemographic, health
      and lifestyle factors. Apart from the fear of losing one's physical health, the
      participants' main fear for self was of losing their independence [20.4% of
      males, 95% confidence interval (CI) = 18.5-22.3%; 34.5% of females, 95% CI = 32.3
      36.4%], with a specific fear of nursing home admission (4.9% of males, 95% CI =
      3.9-5.9%; 9.5% of females, 95% CI = 8.3-10.6%), with confidence intervals
      indicating a significantly higher prevalence of both in females. Living alone was
      significantly associated with fear of loss of independence in females only [odds
      ratio (OR) = 1.62, 95% CI = 1.38-1.90], and with fear of admission to a nursing
      home in both males and females (OR = 1.82, 95% CI = 1.16-2.85 in males; OR =
      1.42, 95% CI = 1.08-1.89 in females). This is the first population-based survey
      that has elicited fears for the future in older Australians. The findings
      presented here provide quantitative evidence to support policies and expansion of
      practices that enable older people to remain in the community for as long as
      possible, rather than enter institutional care prematurely. They also emphasise
      that, while a large proportion of older people are concerned about losing their
      independence, only a small minority have specific concerns about nursing home
      admission.

PMID- 17444985
TI  - The right tool for the task: 'boundary spanners' in a partnership approach to
      tackle fuel poverty in rural Northern Ireland.
AB  - To date, research on fuel poverty has largely focused on the outcomes of
      interventions, with little attention being accorded to intervention processes. In
      reporting on an evaluation of a fuel poverty intervention in rural Northern
      Ireland, the present authors explore some of the mechanisms that secured the
      project's perceived success. Specifically, they focus on the role of the
      'boundary spanner', a concept that is increasingly applied to the analysis of
      local health partnerships. Initiated by a health action zone (HAZ), the project
      was implemented by a partnership of 21 organisations from the statutory,
      community and voluntary sectors. The role of the HAZ manager was described as
      ensuring that partners stayed engaged, that the project secured support from
      organisations and that it impacted on policy-makers. A full-time community energy
      advisor carried responsibility for the partnership's communication with the
      recipient communities. She worked closely with community associations and project
      recipients. The project was consistently described by stakeholders as community
      led and as having been very successful. The authors suggest that this was because
      of the roles of two individuals who, at different levels, communicated and
      negotiated with partners and recipients, maintained momentum, and facilitated the
      ongoing involvement of the communities. The literature on boundary spanners
      usually focuses on how the role enables organisations from a range of sectors to
      participate in partnerships and tackle issues outside the remit of single
      organisations. As such, it usually describes spanning boundaries 'across and
      upwards'. While such insight is important and valuable, this study shows that a
      fuller understanding of the success or failure of local partnership interventions
      can be gained by also exploring the process of spanning 'downwards'. The authors
      conclude that, by extending the concept of the boundary spanner to include
      spanning 'downwards', the concept's explanatory power is enhanced.

PMID- 17444986
TI  - Survey of the perceived professional, educational and personal needs of
      physiotherapists in primary care and community settings.
AB  - The emphasis of UK Government policy on primary-care-based services has led to
      more physiotherapists working in the community. The aims of the present study
      were to identify the perceived professional, educational and personal needs of
      community physiotherapists, and to determine good practice in meeting these
      needs. A survey of physiotherapists working in 15 National Health Service
      community trusts in the West Midlands was carried out in September 2000. The
      survey questionnaire was developed through focus groups and mailed to a random
      sample of 200 community physiotherapists. The response rate was 67%, and the
      median age group of the respondents was 21-30 years. The participants worked
      mainly in 'urban but not inner city' areas, most commonly in domiciliary (31%, n
      = 38) and general practitioner surgery/health centre (26%, n = 32) locations.
      Fifty-one per cent (n = 66) of respondents had no specific learning objectives
      for continuing professional development (CPD); those with such objectives were
      more positive as to their helpfulness than those without them (Mann-Whitney U
      test z = 2.519, P = 0.012). Fifty-three per cent (n = 68) also often/very often
      found it problematic getting cover for their caseloads so that they could take
      part in CPD activities. Access to library resources and use of computers were
      problems, as were confidence in appraising literature and opportunities to
      discuss research evidence with colleagues. Fifty-nine per cent (n = 77) of
      respondents indicated that they often/very often felt stressed by the size of
      their caseloads. Colleague support included mentorship, peer review, journal
      clubs, clinical interest groups and multidisciplinary in-service training;
      respondents with experience of these resources expressed more positive attitudes
      to them than those without (Mann-Whitney U-test z = 2.871, P < 0.0005 for each).
      Forty-two per cent (n = 54) indicated that there were problems with safety
      issues. This study has identified needs that will have an impact on the ability
      of community physiotherapists to meet the demands of clinical governance.
      National Health Service management at all levels has a responsibility to
      facilitate the education, training and support of community physiotherapists.

PMID- 17444987
TI  - Too frightened to care? Accounts by district nurses working with clients who
      misuse substances.
AB  - Drug misusers have complex health and social care needs, and experience
      considerable difficulties in accessing the assessment, care and treatment that
      they require. Despite the development of specialist services in many parts of the
      UK, substance misuse is often marginalised within mainstream general healthcare,
      and many practitioners are unprepared for the challenges of working with this
      client group. The present paper reports findings from a qualitative study that
      aimed to explore district nurses' understandings and practices in relation to
      discrimination and inequalities issues. The research took place during 2003 in
      two city-based primary care trusts in the North of England. Semistructured
      interviews were undertaken with 18 'G' grade district nurses. The authors present
      findings that highlight some of the challenges and tensions district nurses
      encounter when providing care to clients who misuse substances. The discourses of
      'prejudice' and 'risk' were intertwined throughout the data, and served to shape
      service provision for clients who misuse substances. This was reflected in the
      district nurses' accounts of their own practice and that of other services,
      suggesting that these clients receive suboptimal care. The discourse of 'risk'
      was also used by district nurses to construct themselves as 'vulnerable', and
      this helped to explain some of their own practices of care provision. Many
      participants acknowledged their limited knowledge and experience of working with
      this client group. There is an urgent need for district nurses and other health
      professionals to develop their practice with these clients, who may present as
      both vulnerable and dangerous, in order to ensure that care is provided equitably
      and safely.

PMID- 17444988
TI  - Mothers experiencing homelessness: mental health, support and social care needs.
AB  - Little is known about the experiences of mothers who become homeless. The numbers
      of women with children in this situation are growing, most becoming homeless
      following domestic or neighbour abuse, or the breakdown of family relationships.
      This qualitative study aimed to describe mothers' experiences of homelessness in
      relation to their mental health, support and social care needs. Twenty-eight
      homeless women with dependent children residing in hostels were interviewed. The
      experience of homelessness was stressful, but viewed as a respite for many of the
      participants because they had experienced violence and harassment prior to their
      stay in the hostels. Many described poor mental health, which they related to the
      conditions in hostels and traumas that they had experienced before becoming
      homeless. Their experiences and perceptions of the services available were mixed.
      Some valued the support offered by staff and other residents, but the majority
      felt that there was a lack of resources to address their needs. Many women had
      difficulty coping with homelessness, and several said that support from other
      homeless women was an important source of help. Services need to work together to
      meet the multiple health, social, psychological and housing needs of these women.

PMID- 17444989
TI  - Delivery complications and healthcare-seeking behaviour: the Bangladesh
      Demographic Health Survey, 1999-2000.
AB  - Maternal health services have a potentially critical role in the improvement of
      reproductive health. The use of health services is related to the availability,
      quality and cost of the services, as well as to social structure, health beliefs
      and the personal characteristics of the users. The present paper examined the
      factors that influence the use of maternal health services for some selected
      pregnancy-related complications (e.g. prolonged labour, excessive bleeding, high
      fever/discharge and convulsions) in Bangladesh by using data from the Bangladesh
      Demographic Health Survey, 1999-2000. It was found that younger mothers were
      significantly less likely to seek professional healthcare at the time of birth.
      The odds for rural women seeking healthcare services from a doctor, nurse and/or
      midwife were half those of urban women. The strong influence of the mothers'
      education and parity on the utilisation of healthcare services is consistent with
      findings from other studies. The possession of assets emerged as an important
      predictor of seeking care from health professionals at the time of birth. Another
      factor, i.e. a husband's concern about pregnancy complications, showed a
      significant and positive impact on the utilisation of healthcare services, which
      is very important for rural women when they are dependent on their spouses. It
      was observed that the respondents living in urban areas, who had higher levels of
      education and lower parity, and more assets (used as a proxy for income), visited
      trained healthcare providers more often and were more likely to use healthcare
      facilities provided by trained personnel at the time of delivery. This is a
      reflection of the fact that, irrespective of their needs, only people from higher
      economic or educational groups can afford to seek healthcare from trained
      personnel in Bangladesh. In other words, predisposing and enabling factors appear
      to have a strong association with women's healthcare utilisation during
      pregnancy.

PMID- 17444990
TI  - Equine-assisted psychotherapy: a mental health promotion/intervention modality
      for children who have experienced intra-family violence.
AB  - Equine-assisted psychotherapy (EAP) is a specialized form of psychotherapy using
      the horse as a therapeutic tool. This modality is designed to address self-esteem
      and personal confidence, communication and interpersonal effectiveness, trust,
      boundaries and limit-setting, and group cohesion. Substantial numbers of children
      witness family violence. There is evidence that violence between parents has
      adverse effects on the children in the family. These children are at greater risk
      of behavioural problems and mental health disorders, including anxiety, anger,
      depression and suicidal ideations, withdrawal, low self-esteem, and attention
      deficit hyperactivity disorder. The purpose of the present pilot study was to
      test the efficacy of EAP in a cross-sectional group of children referred to a
      psychotherapist for various childhood behavioural and mental health issues over
      an 18-month period (June 2003-January 2005). Sixty-three children received a mean
      number of 19 EAP sessions. Scores on the Children's Global Assessment of
      Functioning (GAF) Scale were determined pre- and post-treatment. The mean (+/-
      standard deviation, SD) pretreatment score was 54.1 (SD 3.2) and post treatment
      mean score was 61.7 +/- 5.0 (t = 9.06, d.f. = 96, P < 0.001). All children showed
      improvement in GAF scores, and there was a statistically significant correlation
      between the percentage improvement in the GAF scores and the number of sessions
      given (r = 0.73, P = 0.001). Univariate analysis showed that the greatest
      improvement in the GAF scores occurred in the youngest of the subjects. Children
      in the group who had a history of physical abuse and neglect had a statistically
      significant greater percentage improvement in GAF scores after treatment than
      those who did not have a history of abuse and neglect. This study has
      demonstrated a quick response to EAP, especially in younger children, but it
      remains to be determined what kind of long-term effects this type of intervention
      may provide.

PMID- 17445002
TI  - On ethics in the profession of dentistry and dental education.

PMID- 17445003
TI  - Managing the curriculum--for a change.
AB  - This article reports the model used to design a new dental curriculum, the design
      process used and its underlying rationale. The evidence base for the process is
      reviewed and discussed. Some suggestions are offered for those engaged in
      developing new curricula. The main conclusions drawn are that the design process
      needs to be managed openly and democratically; the alignment model is the most
      appropriate for designing dental curricula; the process of curriculum design is
      inextricably linked to organisational development; and the concepts of learning
      organisations, communities of practice and culture all have their part to play in
      the process of introducing deep innovations, such as new curricula'.

PMID- 17445004
TI  - Development of an open case-based decision-support system for diagnosis in oral
      pathology.
AB  - BACKGROUND: Making diagnoses in oral pathology are often difficult and confusing
      in dental practice, especially for the less-experienced dental student. One of
      the most promising areas in bioinformatics is computer-aided diagnosis, where a
      computer system is capable of imitating human reasoning ability and provides
      diagnoses with an accuracy approaching that of expert professionals. This type of
      system could be an alternative tool for assisting dental students to overcome the
      difficulties of the oral pathology learning process. This could allow students to
      define variables and information, important to improving the decision-making
      performance. However, no current open data management system has been integrated
      with an artificial intelligence system in a user-friendly environment. Such a
      system could also be used as an education tool to help students perform
      diagnoses. The aim of the present study was to develop and test an open case
      based decision-support system. METHODS: An open decision-support system based on
      Bayes' theorem connected to a relational database was developed using the C++
      programming language. The software was tested in the computerisation of a
      surgical pathology service and in simulating the diagnosis of 43 known cases of
      oral bone disease. The simulation was performed after the system was initially
      filled with data from 401 cases of oral bone disease. RESULTS: The system allowed
      the authors to construct and to manage a pathology database, and to simulate
      diagnoses using the variables from the database. CONCLUSION: Combining a
      relational database and an open decision-support system in the same user-friendly
      environment proved effective in simulating diagnoses based on information from an
      updated database.

PMID- 17445005
TI  - Early patient contact in undergraduate dental education in Germany--'The
      Greifswald Model'.
AB  - Revised regulations in Germany have allowed new curricular concepts to be
      introduced into the undergraduate dental curriculum. In the first 2 years of the
      dental curriculum at the University of Greifswald, a new teaching concept which
      is based on the interactions between Community Medicine and Dentistry has been
      introduced. It emphasises the importance of early patient contact in providing
      experience for students. The course consists of three principal elements: student
      patient contacts in the patient's home; problem-based learning tutorials to
      discuss patient cases; and special training in communication skills. The aim of
      the course is to give students an insight into the patient's view of the illness
      and treatment, and the effect of their condition on his or her lifestyle. The
      students also learn about the communal perspective (health survey, intervention
      planning and implementation in a community). The first four courses were
      evaluated by questionnaires from the students before and after the 2-year course
      to assess the concept from the students' perspective. The results indicate that
      it is possible to provide considerable improvement of the medical/dental
      education as regards communication skills and understanding of the patients'
      perceptions, by letting the student establish contact with patients at the very
      beginning of the curriculum.

PMID- 17445006
TI  - Stress levels of dental students at the Fiji School of Medicine.
AB  - INTRODUCTION: The Fiji School of Medicine is the primary health care educational
      institution in Fiji and possesses the only dental school in the Pacific. The oral
      health programme is a multi-entry/exit programme. The aim of this study was to
      determine the perceived sources or stress and at risk groups within the
      undergraduate oral health care programmes. METHODS: A modified version of the
      Dental Environment Stress questionnaire was used to assess levels of stress for
      41 items. RESULTS: A total of 115 undergraduate students participated (response
      rate = 84%). Of the respondents, 54% were male and 46% were female; 55% were Indo
      Fijians, 18% Indigenous-Fijians, 8% Polynesians, 7% Micronesians, whilst
      Melanesians and others were each 6%. Moderate to severe stressful items were:
      full loaded day, followed by criticism from clinical supervisors in front of
      patients, amount of assigned work, fear of failing a course or year, examination
      and grades, financial resources, fear of employment after graduation and fear of
      facing parents after failure. Of the questionnaire items, 24% had significant
      differences across year groups. Overall, third years were most stressed followed
      by fourth years, fifth years, first years and second years. Indo-Fijians were the
      most stressed, followed by Indigenous-Fijians, Polynesians, others and
      Melanesians. Females were significantly more stressed than males for 27% of
      items. Private fee-paying students were more stressed than sponsored students.
      CONCLUSION: Overall stress levels were slight to moderate and were higher in
      senior years, Indo-Fijians, females and private fee-paying students.

PMID- 17445007
TI  - Viral hepatitis among male amphetamine-inhaling abusers.
AB  - BACKGROUND: Few studies have focused on the clandestinely consumed amphetamine as
      a primary drug. The purpose of this study was to estimate the prevalence of
      hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and the related
      factors in male amphetamine-inhaling abusers. METHODS: This was a cross-sectional
      study. From November 2004 to February 2005, 285 amphetamine-inhaling male
      subjects at one prison in Taiwan and 285 age-matched healthy men without history
      of using illicit drugs or tattooing were enrolled. A face-to-face interview
      focusing on amphetamine-addicted history and sociodemographic information was
      used. Hepatitis B surface antigen (HBsAg) and anti-HCV were tested. RESULTS: The
      mean age of the subjects was 34.1 +/- 8.6 years (range 17-75 years). Among 285
      subjects, 13.3% were positive for HBsAg, 20.0% positive for anti-HCV and 2.5%
      positive for combined HBsAg and anti-HCV. Multivariate logistic regression
      analysis showed that tattoo (odds ratio (OR) 2.97, 95% confidence interval (CI)
      1.37-6.43) and elevated alanine aminotransferase (ALT) (OR 3.15, 95% CI 1.49
      6.66) were independently related to persons being anti-HCV positive. Elevated ALT
      was related to persons being HBsAg positive (OR 2.60, 95% CI 1.15-5.89).
      CONCLUSION: Screening of HBV and HCV infection among amphetamine-inhaling abusers
      remains necessary. Tattoo and elevated ALT are identified as the related factors
      for being anti-HCV positive. Elevated ALT is the related factor for being HBsAg
      positive.

PMID- 17445008
TI  - Changes in medication use from age 26 to 32 in a representative birth cohort.
AB  - BACKGROUND: To date, longitudinal studies of medications have been confined to
      older adults or clinical samples, with no data from prospective studies of
      younger adults. The aim of the study was to examine changes in medication usage
      between ages 26 and 32 in a prospective study of a representative birth cohort.
      METHODS: Medication use during the previous 2 weeks was investigated among 960
      individuals at ages 26 and 32. RESULTS: Nearly two-thirds took at least one
      medication at each age, with medication prevalence higher among women than among
      men. Three-quarters of those taking at least one at age 26 were doing so at 32.
      Over-the-counter medication prevalence increased from 35 to 43% between 26 and 32
      years of age. Although the prevalence of prescribed medications decreased (from
      just under half to just over one-third, and from two-thirds to below half among
      women), there was no significant difference between the ages once hormonal
      contraceptives were accounted for. By 32, reduced usage of hormonal
      contraceptives was apparent, with one-third of age-26 users still taking these at
      32. Other categories showing major changes were analgesics (increased), anti
      asthma drugs (decreased), antidepressants (increased) and antiulcer drugs
      (increased). At 32, 82% of those taking analgesics, 85% of those taking nutrient
      supplements, 71% of those taking antihistamines and 33% of those taking antiulcer
      drugs had self-prescribed them. CONCLUSION: A considerable proportion of the
      sample used medications by age 32, and there was considerable change between 26
      and 32. The changes are likely to have been due to a mix of ageing and period
      effects.

PMID- 17445009
TI  - Patient perceptions of osteomyelitis, septic arthritis and prosthetic joint
      infection: the psychological influence of methicillin-resistant Staphylococcus
      aureus.
AB  - INTRODUCTION: Patients form their own representations of their illness, which can
      be important determinants of their coping and influence outcome. Our aims were to
      (i) assess patient perceptions of osteomyelitis, septic arthritis and prosthetic
      joint infection, (ii) compare perceptions of methicillin-resistant Staphylococcus
      aureus (MRSA) with non-MRSA infection and (iii) investigate the emotional aspects
      of these infections. METHODS: A questionnaire was developed from the 'Illness
      Perception Questionnaire' of Weinman et al.with additional questions assessing
      emotional response. This was offered to all patients with osteomyelitis, septic
      arthritis and prosthetic joint infection attending the Liverpool Hospital
      Infectious Diseases Outpatient Clinic during a 3-month period. RESULTS: There
      were 91 respondents--25 with MRSA infection, 14 with MRSA colonization and 52
      without MRSA. Seventy-nine per cent of all respondents felt that their infection
      was very serious and 76% felt their infection had had major consequences on their
      life. On multivariate analysis MRSA was associated with a greater emotional
      effect; the consequences and emotional effects of infection were greater in
      younger people and prosthetic joint infection was associated with less sense of
      control or cure. CONCLUSION: Osteomyelitis, septic arthritis and prosthetic joint
      infection have a significant effect on an individual. Ongoing support and
      education are important, particularly for the young, those with prosthetic joint
      infection and patients with MRSA.

PMID- 17445010
TI  - Weather: driving force behind the transmission of severe acute respiratory
      syndrome in China?
AB  - BACKGROUND: The association between weather and severe acute respiratory syndrome
      (SARS) transmission in Beijing and Hong Kong in the 2003 epidemic was studied to
      examine the effect of weather on SARS transmission. METHODS: Pearson's
      correlation analyses and negative binomial regression analyses were used to
      quantify the correlations between the daily newly reported number of SARS cases
      and weather variables, using daily disease notification data and meteorological
      data from the two locations. RESULTS: The results indicate that there were
      inverse association between the number of daily cases and maximum and/or minimum
      temperatures whereas air pressure was found to be positively associated with SARS
      transmission. CONCLUSION: The study suggests that weather might be a contributory
      factor in the 2003 SARS epidemic, in particular in the transmission among the
      community members.

PMID- 17445011
TI  - Results of primary percutaneous coronary intervention in a consecutive group of
      patients with acute ST elevation myocardial infarction at a tertiary Australian
      centre.
AB  - BACKGROUND: Multicentre randomized controlled trials (RCT) of primary
      percutaneous coronary intervention (PCI) for ST elevation myocardial infarction
      (STEMI) have consistently shown lower mortality compared with fibrinolysis, if
      carried out in a timely manner. Although primary PCI is now standard of care in
      many centres, it remains unknown whether results from RCT of selected patients
      are generalizable to a 'real-world' Australian setting. The primary goal of this
      study was to evaluate whether a strategy of routine invasive management for
      patients with STEMI can achieve 30-day and 12-month mortality rates comparable
      with multicentre RCT. Secondary goals were to determine 30-day mortality rates in
      prespecified high-risk subgroups, and symptom-onset- and door-to-balloon
      inflation times. METHODS: A retrospective observational study of 189 consecutive
      patients treated with primary PCI for STEMI in a single Australian centre
      performing PCI for acute STEMI. RESULTS: All-cause mortality was 6.9% at 30 days,
      and 10.4% at 12 months. Mortality in patients presenting without cardiogenic
      shock was low (2.4% at 30 days; 5.0% at 12 months), whereas 12-month mortality in
      patients with shock was higher, particularly in the elderly (29.4% for patients
      <75 years; 85.7% for patients > or =75 years, P = 0.01). Symptom-onset-to-balloon
      inflation time was < or =4 h in 56% of patients (median 231 min); however, a door
      to-balloon time of <90 min was achieved in only 20% (median 133 min). CONCLUSION:
      Mortality and symptom-onset-to-balloon-inflation times reported in RCT of primary
      PCI for STEMI are generalizable to 'real-world' Australian practice; however,
      further efforts to reduce door-to-balloon times are required.

PMID- 17445012
TI  - Postural orthostatic tachycardia syndrome: an underrecognized disorder.
AB  - BACKGROUND: Postural orthostatic tachycardia syndrome (POTS), a clinical syndrome
      of orthostatic intolerance characterized by excessive tachycardia and symptoms of
      cerebral hypoperfusion on standing, is not well recognized in Australia. The aim
      was to study the clinical symptomatology, results of autonomic testing and
      outcome in patients with POTS. METHODS: Sixteen subjects from a tertiary referral
      centre who met the criteria for POTS were studied between January 2003 and
      January 2006. Ten of these patients consented to be interviewed using a validated
      autonomic symptom questionnaire. Heart rate responses to deep breathing and the
      Valsalva manoeuvre were measured using Colin BP-508 machine (WR Medical
      Electronic Co., Stillwater, MN, USA). Tilt studies were carried out for 10 min to
      80 degrees of head-up tilting. Patient outcome was assessed as functionally
      normal, able to stand 30 min without symptoms, able to work and carry out
      recreational activities or worse on follow up. RESULTS: The mean age of 10
      subjects was 24.9 +/- 6.8 years, six being women. The mean duration of symptoms
      was 70.7 months (range 3-228 months). The common presenting orthostatic symptoms
      were light-headedness (100%), palpitations (90%), pallor (90%), weakness (80%)
      and clammy skin (80%). The mean heart rate increment during the tilt study was
      51.7 +/- 14.3 b.p.m. The mean duration of follow up was 8.9 months (range 1-16
      months). Only five patients were functioning normally at the follow-up visit.
      CONCLUSION: POTS is an underrecognized but persistent autonomic disorder in young
      patients with a variety of symptoms and variable outcome.

PMID- 17445013
TI  - Competencies and skills for remote and rural maternity care: a review of the
      literature.
AB  - AIM: This paper reports a review of the literature on skills, competencies and
      continuing professional development necessary for sustainable remote and rural
      maternity care. BACKGROUND: There is a general sense that maternity care
      providers in rural areas need specific skills and competencies. However, how
      these differ from generic skills and competencies is often unclear. METHODS:
      Approaches used to access the research studies included a comprehensive search in
      relevant electronic databases using relevant keywords (e.g. 'remote',
      'midwifery', 'obstetrics', 'nurse-midwives', education', 'hospitals', 'skills',
      'competencies', etc.). Experts were approached for (un-)published literature, and
      books and journals known to the authors were also used. Key journals were hand
      searched and references were followed up. The original search was conducted in
      2004 and updated in 2006. FINDINGS: Little published literature exists on
      professional education, training or continuous professional development in
      maternity care in remote and rural settings. Although we found a large literature
      on competency, little was specific to competencies for rural practice or for
      maternity care. 'Hands-on' skills courses such as Advanced Life Support in
      Obstetrics and the Neonatal Resuscitation Programme increase confidence in
      practice, but no published evidence of effectiveness of such courses exists.
      CONCLUSION: Educators need to be aware of the barriers facing rural
      practitioners, and there is potential for increasing distant learning facilitated
      by videoconferencing or Internet access. They should also consider other
      assessment methods than portfolios. More research is needed on the levels of
      skills and competencies required for maternity care professionals practising in
      remote and rural areas.

PMID- 17445014
TI  - Effects of nursing interventions within an integrated care pathway for patients
      with hip fracture.
AB  - AIM: This paper reports a study to evaluate the contribution of nursing care
      within an integrated care pathway for patients with hip fracture. BACKGROUND:
      There is growing interest in quality assurance in health care. Integrated care
      pathways are a method to achieve this goal, and are a multi-professional team
      approach where the requirement for nurses to work effectively within the team is
      important. However, the nurses' role and contribution within the team have not
      been well described. METHOD: A quasi-experimental, prospective study comparing an
      intervention group with a comparison group was carried out. One hundred and
      twelve independently living patients, aged 65 years or older and admitted to a
      Swedish hospital with a hip fracture, were consecutively selected. Pathological
      fracture and severe intellectual impairment (Pfeiffer's test <3 points) served as
      exclusion criteria. The intervention was designed to focus on patients'
      motivation and their prerequisites for rehabilitation and was based on the
      concept of transition. The main outcome measure was the number of patients
      restored to preoperative activities of daily living levels in 2003-2004.
      FINDINGS: In the intervention group 21% were restored to activities of daily
      living to level A (independent) at discharge, whereas only 5% in the comparison
      group were restored to this level. No patients in the intervention group,
      admitted as independent, remained at activities of daily living level F
      (dependent), whereas 16% remained at level F in the comparison group (P=0 x 003).
      CONCLUSION: When admitting older patients with a hip fracture, it is important to
      acquire good knowledge about each patient and their prerequisites and to offer
      them accelerated rehabilitation in accordance with their individual ability. By
      monitoring process indicators during the transition, serious deviations from the
      care plan can be avoided.

PMID- 17445015
TI  - Penicillin sensitivity among hospital nurses without a history of penicillin
      allergy.
AB  - AIM: This paper reports a study to document the prevalence of penicillin
      sensitivity among nurses who had no previous history of sensitivity and worked in
      an inner city hospital in Turkey. BACKGROUND: Frequent and prolonged exposure to
      any drug including penicillin may increase the risk of hypersensitivity to these
      drugs. Local administration of drugs increases the likelihood of sensitization.
      Nurses are the main group of healthcare workers who prepare and administer
      antibiotics to patients, so they may be at highest risk for sensitization. Skin
      testing with major and minor determinants of penicillin has proved useful for
      identifying penicillin-specific IgE antibodies in sensitized individuals. METHOD:
      Skin prick tests were performed with benzyl penicilloyl polylysine (PPL) and a
      mixture of minor antigenic determinants (MDM) solution with 83 nurses who had
      been handling beta-lactam antibiotics. The study was conducted in 2004. FINDINGS:
      Ten nurses (12%) had positive skin reactions to penicillin antigens. Six were
      sensitive to PPL (7 x 2%) and four were sensitive to MDM (4 x 8%). CONCLUSION:
      Occult sensitization to beta-lactam antibiotics, without symptoms, may develop in
      hospital nurses. It is possible that these healthcare workers might be at
      increased risk of hypersensitivity reactions should they be exposed to beta
      lactams, administered for therapeutic purposes. Further research is needed to
      explore this important issue.

PMID- 17445016
TI  - Accuracy of nurses' perceptions of voice hearing and psychiatric symptoms.
AB  - AIM: This article reports a study of nurses' assessments of a voice hearer's
      voices and psychiatric symptoms, and associations of these perceptions with
      nurses' education, career experience and primary care role. BACKGROUND:
      Traditional views in nursing suggest that to engage voice hearers in a discussion
      of their voices is to support the psychopathology of the voice hearers. Research
      into how voice hearers conceptualize voice hearing has generated a range of
      perspectives, raising concerns about whether nurses capture sufficient, accurate
      and specific assessment data about the experiences of voice hearers. METHOD: One
      hundred and fifteen psychiatric nurses rated items on an Inventory of Voice
      Experiences and the Brief Psychiatric Rating Scale while viewing a videotaped
      assessment of a voice hearer with serious and persistent mental illness. The
      voice hearer in the videotape used the same instruments to rate his own voices
      and symptoms. This self-assessment was undertaken 30 days before and immediately
      before production of the video-recorded assessment. The data were collected
      between 2000 and 2002. RESULTS: The voice hearer's ratings of his voice hearing
      experiences and psychiatric symptoms were consistent over a 30-day period. Most
      nurse ratings of the voice hearer's voices and psychiatric symptoms did not match
      those of the voice hearer. However, the voice hearer and nurses demonstrated a
      moderately positive association between the voice hearer's voices and symptoms.
      Ratings of graduate-educated case managers and clinical nurse specialists (n=30)
      in clinical practice settings were more consistent with one another and
      corresponded more closely with the ratings of the voice hearer, particularly for
      the association between the voice hearer's voices and symptoms. CONCLUSION:
      Accurate and specific assessment of voice hearing may facilitate engagement with
      voice hearers and improve the selection of strategies to help them manage the
      voices that upset them.

PMID- 17445017
TI  - Aggressive behaviour on acute psychiatric wards: prevalence, severity and
      management.
AB  - AIM: This paper reports a study to investigate the nature and prevalence of
      inpatient aggressive behaviour directed at staff and other patients and, in the
      case of patient self-harm, the methods used by nursing staff to manage this.
      BACKGROUND: Aggressive behaviour poses a threat to the physical and psychological
      health of psychiatric nursing staff. The fear that results from working in a
      climate of potential danger can also have a damaging impact on patient care.
      METHODS: Nursing staff on five acute inpatient wards in one hospital in the
      United Kingdom collected data on aggressive incidents using the Staff Observation
      Aggression Scale - Revised during a 10 month period from June 2001 to April 2002.
      RESULTS: There were 254 incidents of aggression recorded. Staff were most
      commonly targeted and were involved in 57 x 1% of incidents. The most frequent
      provocation of the aggression was the patient being denied something such as
      leave from the ward (29 x 5% of incidents). The most frequent means used by
      patients was verbal aggression (60% of incidents), the most frequent outcome for
      the victim was feeling threatened (59% of incidents), and verbal interventions
      were used most frequently to manage the aggressive behaviour (43 x 7%). Despite
      many incidents involving verbal aggression in both staff- and patient-targeted
      aggression, 35 x 9% of incidents involving staff and 25% of incidents involving
      other patients resulted in seclusion. CONCLUSION: It is estimated that in a 12
      month period at the hospital in this study a nurse would have a one in 10 chance
      per year of receiving any kind of injury as a result of patient aggression.
      Despite the predominance of verbal over physical aggression, the fear generated
      from working in such an environment and a difficulty in understanding the causes
      of patient aggression may motivate staff to manage aggressive incidents with
      physical methods such as seclusion and restraint on a frequent basis.

PMID- 17445018
TI  - Turkish adaptation of the parental health beliefs scale.
AB  - AIM: This paper reports an adaptation of the English version of the Parental
      Health Beliefs Scale for use with Turkish parents and an evaluation of its
      psychometric properties. BACKGROUND: As a profession, nurses are particularly
      concerned with cross-cultural influences that affect the health beliefs of
      populations. Although the international literature describes questionnaires and
      specific scales in health promotion and health beliefs, adequate Turkish-language
      instruments are scarce. Therefore, suitable instruments need to be developed or
      adapted for the Turkish parents. METHOD: This was a psychometric study. A
      convenience sample (n=257) was recruited in 2003 from parents who attended a
      primary healthcare centre in Erzurum, Turkey. Translation and back-translation of
      the original English instrument and content validation by an expert panel were
      the first two steps. The third step was psychometric testing of the adapted
      instrument to establish internal consistency, inter-item correlation and
      construct validity. Data were collected using the Parental Health Beliefs Scale.
      Socio-demographic data were also collected. The investigators visited the centre
      every workday, and interviewed the samples. The parents read and self-completed
      the questionnaire. FINDINGS: Content validity procedure resulted in a final scale
      that consisted of 20 items. Cronbach's alpha was 0 x 75. Factor analysis yielded
      three factors related to chance, internality and powerful others. CONCLUSION:
      Although acceptable levels of reliability and validity of the Turkish version of
      the Parental Health Beliefs Scale for parents were reached, cultural factors
      appeared to play a role in the applicability of the scale. Further validation
      research is therefore needed before the scale can be recommended for use in
      nursing research and practice.

PMID- 17445019
TI  - Relationship of nurses' spirituality to their understanding and practice of
      spiritual care.
AB  - AIM: This paper reports a study to examine the relationship of nurses'
      spirituality to their understanding and practice of spiritual care. BACKGROUND:
      Continued debate surrounds the concept, practice and teaching of spirituality,
      highlighting the complexity and importance of understanding spirituality and the
      delivery of spiritual care. Spirituality is defined in this study as the
      relationship with the self and a dimension beyond the self. METHOD: A convenience
      sample of 61 nurses from a part-time Bachelor of Science degree programme in
      nursing in Hong Kong, more than half of whom reported their religious
      affiliations, completed a newly developed, 27-item five-point Likert scale
      questionnaire. The data were collected in 2002. Descriptive statistics were
      calculated. Correlations were used to determine relationships among self,
      understanding and practices of spiritual care. The Mann-Whitney U and Kruskal
      Wallis tests were used to examine differences between demographic variables and
      spirituality, understanding and practices of spiritual care. Multiple linear
      regression was used to determine factors contributing to understanding and
      practices of spiritual care. FINDINGS: A positive statistically significant
      correlation was found between self and the following three variables: dimension
      beyond self (r=0.35, P<0.001), understanding of spiritual care (r=0 x 57, P<0 x
      001), and practice of spiritual care (r=0 x 26, P<0 x 05). The relative
      contributions of self to understanding (beta=1 x 06, |t|=10 x 74, P<0.001) and
      practice of spiritual care (beta=0 x 68, |t| = 3 x 62, P=0 x 001) were
      statistically significant. There was no statistically significance difference
      between any of the demographic variables and understanding and practice of
      spiritual care, except for a negative relationship between religious affiliations
      and the dimension beyond self (P<0 x 001). CONCLUSION: Through continuously
      seeking self-awareness and connecting to a dimension beyond the self for inner
      resource, the contented whole self will be able to provide spiritual care.

PMID- 17445020
TI  - Nursing students' perceptions of learning in the clinical setting of the
      Dedicated Education Unit.
AB  - AIM: This paper reports a study to explore nursing students' experience of
      learning in the clinical setting of a Dedicated Education Unit using a
      communities of practice framework. BACKGROUND: The Bachelor of Nursing curriculum
      at the University of Canberra is clinically focused, recognizing the importance
      of learning to be a nurse in and from practice. A communities of practice
      framework underpins the philosophy of the Dedicated Education Unit model of
      clinical practicum. METHOD: In this exploratory qualitative study, a convenience
      sample of 25 second and third year nursing students participated in focus group
      discussions, conducted in 2004, to share their views of learning in the Dedicated
      Education Unit, a newly established model of clinical education. FINDINGS: Three
      major themes were identified: acceptance, learning and reciprocity, and
      accountability. Acceptance of students by clinicians assisted students to engage
      in nursing work. Students acknowledged the importance of peer learning in sharing
      experiences, reinforcing knowledge and enhancing confidence. Students accepted
      responsibility for their work and they valued this responsibility, but some
      questioned whether participation in all aspects of work constituted a learning
      opportunity. CONCLUSION: Engagement and participation in the clinical workplace
      are valuable for nursing students. Strategies to support learning in the
      workplace can be shared with students and clinicians. Further research to test
      the theoretical premises of the communities of practice framework in clinical
      nursing education is required.

PMID- 17445021
TI  - Influence of task properties and subjectivity on consistency of triage: a
      simulation study.
AB  - AIM: This paper reports a study to determine nurses' levels of agreement using a
      standard 5-point triage scale and to explore the influence of task properties and
      subjectivity on decision-making consistency. BACKGROUND: Triage scales are used
      to define time-to-treatment in hospital emergency departments. Studies of the
      inter-rater reliability of these scales using paper-based simulation methods
      report varying levels of consistency. Understanding how various components of the
      decision task and individual perceptions of the case influence agreement is
      critical to the development of strategies to improve consistency of triage.
      METHOD: Simulations were constructed from naturalistic observation, cue types and
      frequencies were classified. Data collection was conducted in 2002, and the final
      response rate was 41 x 3%. Participants were asked to allocate an urgency code
      for 12 scenarios using the Australasian Triage Scale, and provide estimates of
      case complexity, levels of certainty and available information. Data were
      analysed descriptively, agreement between raters was calculated using kappa. The
      influence of task properties and participants' subjective estimates of case
      complexity, levels of certainty and available information on agreement were
      explored using a general linear model. FINDINGS: Agreement among raters varied
      from moderate to poor (kappa=0 x 18-0 x 64). Participants' subjective estimates
      of levels of available information were found to influence consistency of triage
      by statistically significant amounts (F 5 x 68; <or=0 x 01). CONCLUSIONS:
      Strategies employed to optimize consistency of triage should focus on improving
      the quality of the simulations that are used. In particular, attention should be
      paid to the development of interactive simulations that will accommodate
      individual differences in information-seeking behaviour.

PMID- 17445023
TI  - In response to: Beecroft P., Santner S., Lacy M.L., Kunzman L. & Dorsey F. (2006)
      New graduate nurses' perceptions of mentoring: six-year programme evaluation.
      Journal of Advanced Nursing55(6), 736-747.

PMID- 17445022
TI  - Developing a theory-based taxonomy of methods for implementing change in
      practice.
AB  - AIM: In this paper we present a theory-based taxonomy of the methods used to
      implement change in practice. BACKGROUND: Implementation research is
      characterized by inconsistent terminology for the methods employed and
      inattention to differences in the relevance of methods across different
      disciplines. Studies of the effectiveness of implementation have yielded mixed
      results. Positive effects shown have been small. The limited success of many
      efforts to implement change in practice may be due, in part, to the absence of a
      framework to guide the use of implementation methods. METHOD: A provisional
      taxonomy of implementation methods, derived from theory and existing taxonomies,
      was used to content analyse a convenience sample of 43 reports of empirical
      studies of the implementation of one or more research-based practice changes
      involving nurses that had been published between 1995 and 2005. This taxonomy was
      revised throughout the course of analysis to capture more completely the
      information in each report. FINDINGS: Following the analysis, nine of the 11
      methods in the provisional taxonomy were retained, two were removed and five new
      methods were identified. The final taxonomy includes 14 implementation methods
      organized into five categories: (a) increasing coordination; (b) raising
      awareness; (c) persuasion via interpersonal channels; (d) persuasion via
      reinforcing belief that behaviour will lead to desirable results and (e)
      increasing behavioural control. CONCLUSIONS: The taxonomy presented here differs
      from prior taxonomies by focusing on nursing and by providing a clear and
      mutually exclusive guide to implementation methods. By deriving the initial
      coding strategy from theory, the taxonomy links the methods to theoretical
      constructs that may inform the selection of methods across different practice
      changes and settings.

PMID- 17445026
TI  - Human heme oxygenase-1 deficiency: a lesson on serendipity in the discovery of
      the novel disease.
AB  - The first case of human heme oxygenase (HO)-1 deficiency was reported by Yachie
      et al. at our laboratory in the Department of Pediatrics, Angiogenesis and
      Vascular Development, Kanazawa University Graduate School of Medical Science, in
      1999. In the present paper I would like to review this novel disease. Our studies
      into HO-1 deficiency were called by us 'Kanazawa version Project X'. From the
      story of our successful discovery we have learned that serendipity is a very
      important spiritual factor. Serendipity is the making of fortunate and unexpected
      discoveries by chance (from its possession by the heroes in the Persian fairy
      tale The Three Princes of Serendip).

PMID- 17445027
TI  - Variation analysis of beta3-adrenergic receptor and melanocortin-4 receptor genes
      in childhood obesity.
AB  - BACKGROUND: Decreased energy expenditure and increased food intake are principal
      causes for obesity. In the present study, genotypes of beta(3)-adrenergic
      receptor (beta(3)AR) and of melanocortin-4 receptor (MC4R), both of which are
      believed to have a close link to the cause of obesity, were analyzed and compared
      with phenotypes of childhood obesity. METHODS: Thirty-five obese children with
      moderate to severe obesity were enrolled. Direct sequencing of the MC4R coding
      region and pinpoint-polymerase chain reaction were used to detect genomic
      variation in the beta(3)AR gene using peripheral blood-derived DNA. RESULTS:
      Allele frequency of Trp64Arg variation in the beta(3)AR gene in the obese
      subjects was 0.16, which is comparable with that in the healthy general
      population in eastern Asia. Comparison of phenotypical characteristics did not
      show a significant difference between Trp/Trp and Trp/Arg subjects. It was
      notable that body height SD was significantly higher in the Trp/Trp than the
      Trp/Arg subjects (0.93 +/- 1.0 SD vs 0.07 +/- 1.3 SD, P= 0.03). Annual weight
      gains were far beyond a hypothetical fat gain in an Arg64 heterozygote with
      decreased energy consumption, suggesting increased food intake in childhood
      obesity. There was, however, no variation in the MC4R gene despite thorough
      sequencing of the entire coding region. CONCLUSIONS: The Trp64Arg variation in
      the beta(3)AR gene has no relationship to the degree or the incidence of
      childhood obesity. The majority of childhood obesity can be characterized as tall
      stature, more rapid weight gain than that expected by decreased energy
      expenditure. Further investigation is necessary in regard to the increased food
      intake as a major cause of childhood obesity.

PMID- 17445028
TI  - Birthweight and risk factors for cardiovascular diseases in Japanese
      schoolchildren.
AB  - BACKGROUND: Low birthweight (LBW) is associated with an increased risk for
      atherosclerotic coronary heart disease (ACHD) later in life. However, little
      information is currently available on the relationship between birthweight (BW)
      and risk factors for ACHD in children. METHODS: The relationship between BW and
      risk factors for ACHD was evaluated in 330 Japanese children (187 boys and 143
      girls) aged between 7 and 12 years, who underwent screening for lifestyle-related
      diseases in Okinawa, Japan. Routine chemical methods were used to determine the
      serum concentrations of lipids, apolipoproteins, uric acid and glucose. Serum
      insulin and adiponectin were measured by sandwich enzyme-linked immunosorbent
      assay. RESULTS: BW was significantly correlated with serum concentrations of
      adiponectin (r= 0.163, P= 0.003) and uric acid (r=-0.166. P= 0.003), but not with
      insulin, lipids or apolipoproteins. These correlations were still significant
      even after adjusting for age, gender and body mass index (BMI) percentile (BW and
      adiponectin, r= 0.239, P= 0.000; BW and uric acid, r=-0.247, P= 0.000). In
      addition, BW was correlated with high-density lipoprotein-cholesterol (HDL-C)
      only after adjusting for age, gender and BMI percentile (r= 0.117, P= 0.034). In
      a stepwise multiple regression analysis, BW was a significant predictive variable
      for adiponectin and uric acid. However, weight velocity (weight gain/year) was a
      stronger predictive variable than BW for both adiponectin and uric acid. BW was
      not a significant predictive variable for HDL-C. Adiponectin was the strongest
      predictive variable for HDL-C. CONCLUSION: BW is related to serum concentrations
      of adiponectin and uric acid. However, weight velocity was a stronger determinant
      of serum adiponectin and uric acid levels than BW in Japanese schoolchildren.
      Thus, it may be important to control weight gain to prevent the development of
      ACHD in children, especially in children with LBW.

PMID- 17445029
TI  - Usefulness of an age-adjusted body shape index in Korean children and
      adolescents.
AB  - BACKGROUND: The aim of the present paper was to determine the usefulness of an
      age-adjusted anthropometric index of body shape for the assessment of obesity in
      Korean children and adolescents aged 10-15 years. METHODS: The population sample
      was composed of 556 boys and 489 girls who completed an interview survey,
      anthropometry, and medical examination for the Korean National Health and
      Nutritional Survey conducted in 1998. An age-adjusted anthropometric index, body
      shape index standard deviation score (BSI-SDS), was derived from waist-to-hip
      ratio divided by height (WHR/Ht) and its common standard deviation according to
      Asayama et al. (1997). Serum levels of lipids, glucose, and liver function
      markers were defined as abnormal if they were above the 90th percentile of the
      study population. Using logistic regression analysis, the odds ratios of having a
      lipidemic, diabetic, or liver complication on increasing BSI-SDS were estimated.
      RESULTS: For both boys and girls, lipidemic and liver complications had
      statistically significant odds ratios associated with increasing BSI-SDS. With 1
      unit increase in BSI-SDS, the odds ratios of lipidemic complications were 1.5 and
      1.3, respectively, for boys and girls, and the odds ratios of liver complications
      were 1.3 and 1.4, respectively, for boys and girls. CONCLUSIONS: A new measure
      developed by Asayama et al., BSI-SDS, is a useful marker of obesity in addition
      to body mass index among Korean children and adolescents aged 10-15 years.

PMID- 17445030
TI  - Maternal factors in the etiology of fetal malnutrition in Nigeria.
AB  - BACKGROUND: The main objective of the study was to determine the role of maternal
      factors in the etiology of fetal malnutrition (FM) in Nigeria. Neonatal and
      Maternity Units of the Wesley Guild Hospital Ilesa, Nigeria, a unit of the
      Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife was the setting
      for the study. METHODS: This was a prospective study of consecutive, singleton,
      term live babies delivered between January and August 2001. Fetal malnutrition
      was diagnosed using Clinical Assessment of Fetal Nutritional Status (CANS) and
      the score (CANSCORE) adapted by Metcoff. The maternal prenatal record was checked
      and additional history was obtained from the mother. This included history of
      maternal illness and drugs taken during pregnancy. The socioeconomic class of the
      parents was also documented. Nutritional status of the mother was determined
      using mid arm circumference (MAC) and the body mass index (BMI). Babies were
      stratified into babies with FM and babies without FM. The two groups of babies
      were compared. RESULTS: Of the 473 studied, 89 [18.8%] had FM. Maternal factors
      found associated with FM were: lack of antenatal care, young mother (<18 years),
      primiparity, maternal undernutrition (BMI < 18.5 kg/m(2) and MAC < 23.5 cm), low
      socioeconomic status, pregnancy-induced hypertension, antepatum hemorrhage, and
      maternal infections especially malaria, urinary tract infections and HIV (P <
      0.05). CONCLUSION: Improvement in the socioeconomic status of women and good
      antenatal care will reduce most of the maternal factors associated with FM in
      Nigeria. Therefore, antenatal should be made cheap and accessible to all pregnant
      mothers.

PMID- 17445031
TI  - Hindmilk and weight gain in preterm very low-birthweight infants.
AB  - BACKGROUND: Feeding of own mother's milk to preterm very low-birthweight infants
      often results in suboptimal weight gain in these infants for whom energy
      requirements are high but in whom volume tolerance is limited. Therefore the
      purpose of the present paper was to investigate the effect of selective hindmilk
      feeding on the growth of preterm very low-birthweight babies. METHODS: Preterm
      very low-birthweight babies admitted into the Special Care Baby Unit of the Jos
      University Teaching Hospital, Nigeria between April 2000 and July 2001 were
      randomized to hindmilk and composite breast milk feeding for 2 weeks. End-points
      were weight, occipitofrontal head circumference and length. RESULTS: For small
      for-gestational-age babies, the infants fed on hindmilk gained weight at a mean
      rate of 12.92 +/- 10.95 g/kg per day as compared with a mean rate of 5.01 +/-
      17.37 g/kg per day for their controls on composite milk (P < 0.0001). For
      appropriate-for-gestational-age babies, the mean rate of weight gain for the
      hindmilk group was 12.99 +/- 10.75 g/kg per day while that for their controls on
      composite milk was 8.29 +/- 20.56 g/kg per day (P < 0.01). There were no
      significant differences in the rates of increase in length and occipitofrontal
      head circumference between the groups. The lipid content of the hindmilk was 1.6
      fold that of composite milk. CONCLUSION: Preterm very low-birthweight babies fed
      hindmilk had a higher rate of weight gain compared to those fed composite milk.
      It is recommended that the hindmilk fraction of expressed breast milk be
      predominantly used for the feeding of preterm very low-birthweight babies while
      in hospital to help shorten their duration of hospital stay.

PMID- 17445032
TI  - Feasibility of neonatal hearing screening program with two-stage transient
      otoacoustic emissions in Turkey.
AB  - BACKGROUND: The objective of this study was to investigate the incidence of
      hearing loss in neonates and evaluate the feasibility of a two-stage Transient
      Evoked Otoacoustic Emission (TEOAE) screening test. Maternal concerns about
      hearing screening were also studied. METHODS: Neonatal intensive care patients
      and well babies were screened using a two-stage TEOAE test, which was followed by
      an Auditory Brainstem Response (ABR) test for those babies who failed the first
      test twice. RESULTS: In total, 711 neonates were screened. At the end of the two
      TEOAE tests, the cumulative pass rate was 99.3% and false-positive rate was 0.3%.
      Five neonates (0.7%) were referred for the ABR test. Sensorineural hearing loss
      was found in three of them (0.4%). Of these three neonates, one was from the well
      baby nursery and two were from the NICU population. Families generally welcomed
      the screening program, with no refusals. Positive test results have not caused
      important maternal concerns. CONCLUSIONS: Congenital hearing impairment is a
      prevalent disease in Turkey. The two-stage TEOAE program is suitable for the
      neonatal hearing screening program. In general, hearing screening tests do not
      cause notable maternal concerns.

PMID- 17445033
TI  - Normal values for KL-6 in cord venous plasma of neonates.
AB  - BACKGROUND: KL-6 in umbilical cord blood, including from premature infants, and
      perinatal factors that may affect these values have not yet been adequately
      discussed. The authors investigated factors affecting cord venous plasma levels
      of KL-6 in neonates, and to establish a normal range of values for KL-6 in
      neonatal cord blood. METHODS: Cord plasma levels of KL-6 were measured in 75
      neonates, and statistical analysis of factors affecting these levels was
      performed. A normal range for cord plasma KL-6 levels was calculated by
      statistical analysis methods based on guidelines by the National Committee for
      Clinical Laboratory Standards. RESULTS: Data from a total of 75 neonates was
      analyzed. Gestational age ranged from 25 to 40 weeks (median, 33.4 weeks), and
      birthweight ranged from 776 to 3760 g (median, 1944 g). There was no
      statistically significant correlation between cord plasma KL-6 levels with
      gender, gestational age, birthweight, method of delivery, Apgar score 1 min, and
      postnatal respiratory distress. The normal range of values for cord plasma KL-6
      was 44.3-148.2 U/mL (median, 73.0 U/mL). CONCLUSION: The cord plasma levels of KL
      6 were about half the normal values reported in children and healthy adults and
      were not affected by various perinatal factors. The authors' findings suggest
      that plasma KL-6 levels rise when respiratory function is established after birth
      and tend to further increase with age.

PMID- 17445034
TI  - Prenatal diagnosis of isolated non-compaction of the ventricular myocardium:
      study of six cases.
AB  - BACKGROUND: Isolated non-compaction of the ventricular myocardium (INVM) is
      characterized by prominent and excessive trabeculations in one or more
      ventricular wall segments, with deep intertrabecular recesses communicating
      directly with the ventricular cavities. Diagnosis of the disease is based on the
      2-D echocardiographic features. Despite the fact that many cases of INVM have
      been reported in children and adults since the initial description of the
      disease, it has been diagnosed in only a few fetuses up to now. Therefore,
      failure to diagnose on fetal echocardiography is probably more common. There are
      different opinions about diagnosis of INVM on fetal echocardiography. METHOD: In
      the present study, six cases of fetal INVM diagnosed between 1999 and 2004 were
      evaluated for prenatal diagnosis, clinical features and natural course. RESULTS:
      In four cases, diagnosis was made in the prenatal period, and in the other two
      cases it was done on postnatal echocardiography at the first day of life. Careful
      reevaluation of these two patient's fetal echocardiographic recordings confirmed
      the postnatal diagnosis retrospectively. CONCLUSIONS: The examiner should be
      aware of the existence of this rare anomaly. If echocardiographic examination
      shows ventricular hypertrophy and/or poor ventricular function, INVM should be
      considered and in order to see recesses, ventricle walls should be investigated
      by zooming in and comparing frame by frame.

PMID- 17445035
TI  - Child abuse study among Swedish physicians and medical students.
AB  - BACKGROUND: The purpose of the present paper was to examine the attitudes and
      experiences of reporting child abuse and neglect among primary care and hospital
      based physicians and to study the responses of physicians and medical students to
      case vignettes suggestive of possible physical abuse or neglect. METHODS:
      Physicians at the child health centers in Goteborg primary care (n= 44) and the
      general pediatricians at the pediatric hospital (n= 21) in Goteborg answered a
      questionnaire regarding their attitude and experiences reporting child abuse and
      neglect. The physicians and medical students (n= 34) responded to three case
      vignettes in which child abuse and neglect could be suspected. RESULTS: A
      majority of the physicians had reported child abuse and neglect to the social
      services (80%). No differences were found between primary care and hospital-based
      physicians in terms of reporting or attitudes. Two-thirds of the physicians had
      suspected child abuse and neglect and decided not to report, and the major reason
      for not reporting was a lack of confidence in social services organization.
      Twenty-one percent had never reported a child for abuse or neglect during their
      working career. Medical students were more likely to report hypothetical cases
      than physicians. CONCLUSION: Many physicians have reported child abuse to social
      services but also have neglected to do so even when suspecting abuse. It is
      important that medical students' willingness to report is continued when starting
      to work clinically and that all physicians should be continuously educated.

PMID- 17445036
TI  - Increasing rate of childhood tuberculosis in a region of east Croatia.
AB  - BACKGROUND: The incidence of childhood tuberculosis as well as the number of
      children being in contact with persons having tuberculosis has increased in the
      region of Slavonski Brod during the past decade (1993-2003). The region is
      located in east Croatia along the border with Bosnia and close to the besieged
      and destroyed town of Vukovar. The region was heavily involved in recent military
      activities and migrations in Croatia and Bosnia (1991-1995). Before the war, the
      population was reasonably well situated, educated and provided with health
      services. METHODS: Routine clinical and epidemiological methods for the diagnosis
      of tuberculosis were used. RESULTS: A total of 225 cases of tuberculosis were
      discovered among 271 suspected cases in a total number of 19 623 children below
      18 years of age admitted during the last decade to the county hospital (1.38%).
      The number increased from three patients with tuberculosis in 1993 to 59 in 2003.
      Discharge diagnoses were: latent infection 40.1%, specific hilar lymphadenopathy
      22.1%, primary lung tuberculosis 18.0%, postprimary tuberculosis 3.0%, and
      contact with infected person but otherwise normal findings 16.9%. The infection
      was usualy (53.1%) acquired within the family, more often so in younger patients.
      Bacteriological cultures were positive in 19 of 117 patients with tuberculosis
      (16.4%). Antituberculosis drug treatment was carried out to completion in all
      children. Resistance was not encountered. CONCLUSION: The authors attribute high
      incidence of childhood tuberculosis in the region of Slavonski Brod, the second
      highest incidence in Croatia, to the sequellae of migrations during military
      activities in Croatia and Bosnia (1991-1995) and to the post-war recession.

PMID- 17445037
TI  - Adult asthma after non-respiratory syncytial virus bronchiolitis in infancy:
      subgroup analysis of the 20-year prospective follow-up study.
AB  - BACKGROUND: Recent studies have stressed the influence of other viruses than
      respiratory syncytial virus (RSV) in the development of asthma in later childhood
      after bronchiolitis in infancy. However, the virus-specific prognosis until
      adulthood has remained obscure, due to lack of sufficiently long follow-up
      studies. The aim of the present study was to evaluate adult respiratory morbidity
      after bronchiolitis in infancy, focused on cases not caused by RSV. METHODS: A
      total of 54 children hospitalized for bronchiolitis at age <2 years were re
      studied at median age 19 years; 22 with RSV bronchiolitis and 22 with non-RSV
      bronchiolitis outside RSV epidemic were included. RSV etiology was studied by
      antigen and antibody assays on admission. Adult asthma was defined by two ways,
      based on written questionnaire, clinical examination and home peak expiratory
      flow monitoring. Lung function was evaluated by flow-volume spirometry (FVS),
      bronchial reactivity by methacholine inhalation challenge (MIC), and atopy by
      skin prick tests (SPT). RESULTS: In the non-RSV group, asthma by two definitions
      was present in 41-50% (vs 18-27% in RSV group). In logistic regression, adjusted
      for gender, age on admission, current atopy and smoking, non-RSV etiology of
      bronchiolitis, compared with RSV etiology, increased asthma risk by both strict
      (odds ratio [OR], 8.34; 95% confidence interval [CI], 1.18-58.69) and less strict
      (OR, 7.93; 95% CI, 1.14-55.41) criteria. An abnormal result in FVS was present in
      32-41% and in MIC in 48-52% of cases in non-RSV and RSV groups, respectively.
      CONCLUSIONS: Infants with non-RSV bronchiolitis requiring treatment in hospital
      are at an increased risk for subsequent asthma in adulthood.

PMID- 17445038
TI  - Prognosis and pathological characteristics of five children with non-Shiga toxin
      mediated hemolytic uremic syndrome.
AB  - BACKGROUND: The three major signs of hemolytic uremic syndrome (HUS) are
      hemolytic anemia, thrombopenia and acute renal failure. HUS is classified into
      Shiga toxin-mediated HUS (Stx-HUS) and non-Shiga toxin-mediated HUS (nStx-HUS).
      The prognosis of nStx-HUS is reported to be less favorable than that of Stx-HUS.
      Although the association between the prognosis and pathological characteristics
      of HUS have been reported such that the prognosis was considered to be poor for
      thrombotic microangiopathy (TMA) with predominant arterial involvement (arterial
      TMA), good for TMA with predominant glomerular involvement (glomerular TMA) and
      dependent on the extent of necrosis in cases of renal cortical necrosis, it is
      not yet clear whether pathological findings are also related to the renal
      prognosis of nStx-HUS cases. Therefore the purpose of the present paper was to
      analyze renal biopsy findings and prognosis for five children with nStx-HUS.
      METHODS: Clinical records of five cases of nStx-HUS among 74 cases of diagnosed
      HUS were reviewed, and information and data were summarized. RESULTS:
      Histological examination of the kidney led to the diagnosis of arterial TMA in
      three cases, and glomerular TMA and severe renal cortical necrosis in one case
      each. Analysis of the relationship between renal histological findings and the
      prognosis found that three patients with arterial TMA and one patient with severe
      renal cortical necrosis later developed end-stage renal failure while one patient
      with glomerular TMA has continued to show normal renal function. CONCLUSIONS:
      These findings indicate that pathological findings are closely related to the
      prognosis in cases of nStx-HUS.

PMID- 17445039
TI  - Diagnosis of rickets and reassessment of prevalence among rural children in
      northern China.
AB  - BACKGROUND: Rates of rickets from 15.9 to 26.7% have been reported in China.
      METHODS: Combining the methods of epidemiology and the behavioral sciences, this
      study investigated the prevalence of rickets in children in rural Shanxi
      Province, China. A total of 250 children age 12-24 months were examined
      physically for the presence of rickets, blood was drawn for laboratory analysis,
      and X-rays were taken of each child's wrists. RESULTS: Vitamin D deficiency in
      the spring was found among 65.3% of children. Rickets diagnosis relying on
      clinical signs alone determined a rickets prevalence of 41.6%, declining to 17.0%
      in the fall after a summer of sun exposure (chi(2) = 8.356, P = 0.004). But an
      integrated diagnostic method exploiting clinical signs, X-ray and alkaline
      phosphatase levels found the prevalence of active rickets to be 3.7%.
      Furthermore, it was demonstrated that only five clinical signs reflect active
      rickets--wide wrists, frontal bossing, rachitic rosary, Harrison's sulcus, and
      bowed legs. CONCLUSIONS: The prevalence of active rickets in young children in
      northern China is lower than previously reported. Even in poor countries, simple
      tests such as X-rays and alkaline phosphatase can be added to physical
      examination to more accurately diagnose active rickets.

PMID- 17445040
TI  - Postoperative anorectal manometric evaluation of patients with anorectal
      malformation.
AB  - BACKGROUND: Fecal incontinence is a common problem after reconstructive surgery
      for anorectal malformations. The aim of this study was to investigate the
      effectiveness of clinical scores and anorectal manometry in patients, who have
      been operated on for anorectal malformations. METHODS: In total, 18 patients who
      underwent surgery for anorectal malformation between 1999 and 2004 were
      investigated for anal continence. For the assessment of the patients' continence,
      Kelly's clinical scoring, Kiesewetter-Chang scoring, and anorectal manometry were
      used. RESULTS: In the intermediate level anorectal malformations, average anal
      resting pressure was found as 58.16 +/- 8.14 cmH(2)O and in high level anorectal
      malformations was found as 40.16 +/- 17.4 cmH(2)O. In the continence score, good
      according to Kelly and Kiesewetter-Chang scoring systems was an average anal
      resting pressure value of 57.92 +/- 8.57 cmH(2)O and in fair or bad was found as
      32 +/- 12.83 cmH(2)O. There were significant differences between the scoring
      systems anorectal malformation level, and average anal resting pressure values (P
      < 0.05). CONCLUSIONS: Anorectal manometric evaluation of the patients in
      postoperative period with anorectal malformation can give more realistic
      information about the patient continence status in anorectal malformations.

PMID- 17445041
TI  - Lipid profile in children with acute viral hepatitis A.
AB  - BACKGROUND: Most of the knowledge about lipid parameters in acute hepatitis is
      originated from adult studies. In this study, the authors investigated lipid
      profile of children with acute hepatitis A (AVH) at diagnosis and recovery in
      order to observe the behavior of lipid parameters in such children. METHODS: A
      total of 28 children (mean age, 8.2 +/- 2.7 years) with AVH and 20 gender and age
      matched healthy children were included. In addition to the routine tests,
      triglyceride, cholesterol, low-density lipoprotein (LDL), high-density
      lipoprotein (HDL), plasma apo A-I and apo B were studied at diagnosis and
      recovery. RESULTS: Serum triglyceride and apo B level was higher, and apo A-I
      level was lower in patients compared to healthy children (P < 0.01, <0.05 and
      <0.01, respectively). On admission, three children had fulminant hepatic failure
      (FHF). Serum lipid parameters were evaluated in respect with the presence of
      icterus and FHF, and found that apo A-I level was lower in icteric children and
      LDL and apo A-I were lower in FHF compared to others (P < 0.05, P < 0.01 and P <
      0.05, respectively). At recovery, while triglyceride, cholesterol, LDL, and apo B
      decreased (P < 0.01), HDL and apo A-I increased (P < 0.01). Serum apo A-I level
      was inversely correlated with serum ammonia level but was positively correlated
      with serum albumin (P < 0.05). CONCLUSIONS: It was shown that serum triglyceride
      and apo B level increased, but apo A-I level decreased in patients with AVH.
      While cholestasis lowers apo A-I level, severe hepatic damage lowers both apo A-I
      and LDL. These parameters return to normal levels within 30 days. An interesting
      relationship between ammonia and apo A-I deserves further investigations,
      speculatively focused on hepatocyte nuclear factor 4 alpha.

PMID- 17445042
TI  - Long-term aspects of nodular gastritis in children.
AB  - BACKGROUND: Close association of nodular gastritis and Helicobacter pylori
      infection has been initially proved by various studies. There have been some
      studies reporting microscopic and histologic recovery in a short time after
      eradication therapy. But there is not enough data about the long-term course of
      this condition. The aim of this study is to document current clinical conditions,
      presence of H. pylori and results of endoscopic and histologic examination, after
      a long-term period, in children with endoscopically diagnosed antral nodularity.
      METHODS: A total of 35 patients diagnosed as nodular antral gastritis by upper
      gastrointestinal endoscopy during a 2 year period, were invited for re-evaluation
      and re-endoscopy after 3 years. Histopathologically, H. pylori detected ones had
      been treated with standard triple eradication therapy. In total, 27 patients were
      accepted for enrollment in the study. Repeated endoscopy could be performed in
      all 27 patients. RESULTS: The persistence of antral nodularity was detected in 18
      of 27 patients. Decrease in symptoms, absence of symptoms and presence of H.
      pylori infection were detected in 6, 8 and 16 (89%) of them, respectively. There
      was no statistical significance between the first and last endoscopic biopsies
      when activity, atrophy, intestinal metaplasia and presence of follicles were
      regarded. Malt lymphoma could not be detected in any of the patients. CONCLUSION:
      There is a strong association between nodular gastritis and H. pylori. Presence
      of antral nodularity in the long-term period may be related to H. pylori re
      infection. New therapeutic approaches are required for treatment and management
      of the patients diagnosed as nodular gastritis and living in areas endemic for H.
      pylori infection.

PMID- 17445043
TI  - Do acid and bile reflux into the esophagus simultaneously? Temporal relationship
      between duodenogastro-esophageal reflux and esophageal pH.
AB  - BACKGROUND: Duodenogastro-esophageal reflux (DGER) is an important factor in the
      pathogenesis of reflux esophagitis. Animal studies have demonstrated that the
      injurious effect of duodenal juice components depends on pH. The purpose of the
      present study was to investigate the temporal relationship between DGER and
      esophageal pH. METHODS: Seventy-six children with symptoms of gastro-esophageal
      reflux disease (27 without, 31 with mild, 18 with severe esophagitis) underwent
      24 h simultaneous esophageal pH and bilirubin monitoring with Bilitec 2000. The
      recordings were analyzed for (i) pH at the beginning of DGER episodes; (ii)
      relative duration of DGER in eight defined pH intervals of 1 pH unit; and (iii)
      differences in relative duration of DGER between the three groups of children.
      RESULTS: DGER episodes most frequently began at pH between 6 and 7. DGER was
      present in the esophagus across the spectrum of esophageal pH, with the biggest
      relative duration between pH 3 and 5. However, in children without esophagitis
      relative duration of DGER was longest between pH 5 and 6, in children with mild
      esophagitis between pH 4 and 5, while in those with severe esophagitis it was
      between pH 2 and 4 (P < 0.001). CONCLUSIONS: DGER appears across the whole
      esophageal pH spectrum. The more severe the esophagitis, the lower the pH at
      which DGER occurs, resulting in simultaneous damaging effects of acid and
      duodenal juice components.

PMID- 17445044
TI  - Novel mutation of methylmalonyl-CoA mutase gene causing the mut0 form of
      methylmalonic acidemia in a Japanese girl.

PMID- 17445045
TI  - Human uric acid transporter 1 gene analysis in familial renal hypo-uricemia
      associated with exercise-induced acute renal failure.

PMID- 17445046
TI  - Familial antiphospholipid antibody in a child with involuntary movement and
      deterioration.

PMID- 17445047
TI  - Pituitary-adrenal axis suppression due to topical steroid administration in an
      infant.

PMID- 17445048
TI  - Neonatal alkalemia associated with potential hypovolemia in an infant born to a
      severely dehydrated mother.

PMID- 17445050
TI  - Emergency stent implantation into obstructed inferior caval vein in a patient
      with heterotaxy and anomalous hepatic venous drainage.

PMID- 17445049
TI  - Double outlet right ventricle with intact ventricular septum.

PMID- 17445051
TI  - Acute gastric mucosal lesions caused by Helicobacter pylori initial infection.

PMID- 17445052
TI  - Hyperosmolar non-ketotic syndrome in a child associated with l-asparaginase and
      prednisolone.

PMID- 17445054
TI  - Risk factors for protein-energy malnutrition in children under 5 years: study
      from Luangprabang province, Laos.
AB  - BACKGROUND: Laos is one of the poorest countries in which chronic malnutrition is
      highest. The aim of the present study was to determine the prevalence of and to
      identify risk factors associated with protein-energy malnutrition (PEM) in
      children under 5 years of age in Luangprabang province, Laos. METHODS: This cross
      sectional study was undertaken from March to May 2004. Anthropometric
      measurements of 798 children were done and data were transformed into height-for
      age, weight-for-age and weight-for-height ratios. Mothers were also interviewed
      with a semi-structured questionnaire. Anthropometric data were entered into
      Nutstat in Epi-Info 2000 and transferred to SPSS for analysis. RESULTS: There was
      a high prevalence of stunting, underweight and wasting, that is, 54.6%, 35%, and
      6% respectively. It was also noted that children aged 12-23 months and Khmu
      ethnic children had a higher prevalence of stunting (65% and 66%) and underweight
      (45% and 40%), respectively. However, it was also found that boys were more prone
      to be stunted and underweight. Furthermore, restricted intake of meats,
      vegetables during illness, and low maternal education were main risk factors for
      child malnutrition in the study area. CONCLUSION: Socioeconomic-demographic
      factors, low maternal education, poor nutrition knowledge for mother and feeding
      practices for sick children are affecting children's health regarding stunting
      and underweight. It is recommended that an improvement in societal
      infrastructure, better maternal education and nutrition are needed to address the
      child malnutrition issue.

PMID- 17445055
TI  - Nutritional status of low-birthweight ethnic minority infants in Backan province,
      Vietnam.
AB  - BACKGROUND: Birthweight and length have been reported to be important
      determinants of infant growth and future nutritional status. The study aims to
      describe the weight and length growth patterns during the first year of life of
      low-birthweight (LBW) ethnic minority infants in the mountainous province Backan,
      Vietnam. METHODS: A total of 64 LBW and normal birthweight infants of ethnic
      minority mothers were recruited from 2001 to 2002 into a prospective cohort
      study. The weight and length of infants were measured monthly for 1 year. Data on
      nutritional status and feeding practices of the infants were collected from
      monthly health records and face-to-face interviews with mothers while their
      infants were 6 and 12 months of age. RESULTS: Most of the increase in weight,
      length and catch-up to the 10th percentile for LBW infants occurred during the
      first 3 and 6 months for boys and for girls, respectively. After these ages, the
      mean weight and length diverged from National Center for Health Statistics (NCHS)
      reference curves to below the 10th percentile. LBW infants' weight-for-age z
      scores was below the NCHS standard at birth (-2.16 SD), caught up after birth,
      became sustainable by 4 months, fell rapidly from the sixth month, then decreased
      to -2 SD at 12 months of age. LBW infants' length-for-age z-scores increased in
      the first month after birth, decreased in the second month and sharply increased
      again until 5 months of age before decreasing. CONCLUSIONS: For LBW infants, it
      is difficult to achieve the same weight or length curves at 12 months of age as
      the NCHS standard.

PMID- 17445056
TI  - Malnutrition improvement for infants under 18 months old of Dai minority in Luxi,
      China.
AB  - BACKGROUND: Child malnutrition and thiamine deficiency remain a matter of public
      concern in Dai children under 5 years old in Southwest areas of China. The aim of
      the present study was to understand the status and correlates of malnutrition and
      thiamine deficiency in Dai children under 18 months old in Yunnan, China, and to
      explore an effective intervention for improving their nutritional status and
      decreasing the prevalence of malnutrition and thiamine deficiency in Dai
      children. METHODS: Well-trained investigators completed a baseline evaluation
      survey, including questionnaire survey by maternal interviews, child physical
      measurements, lab examination of thiamine, and group discussions in a cross
      sectional study. An intervention plan was constructed by a group consisting of
      the city governor, government officers, maternal and child health workers,
      community leaders, and villagers etc. A comprehensive community-based
      intervention was carried out for 352 children born after July 2001 and their
      mothers or caregivers in half of the baseline survey villages by the end of 2003.
      The intervention included participatory intervention, community nutrition
      education, child growth monitoring and distributing thiamine to new mothers just
      before or after delivery. RESULTS: The baseline evaluation survey in 2000
      indicated that the prevalence of moderate and severe protein-energy malnutrition
      was 19.5% for underweight, 16.4% for stunting, and 6.7% for wasting,
      respectively. With increasing age, the prevalence increased, peaking at 12-15
      months. The prevalence of underweight in girls was higher than in boys. A total
      of 10.5% of children suffered from thiamine deficiency, and 5.7% of the children
      were insufficient in thiamine supply. Low Kaup target (<25%) was significantly
      associated with lack of guidance by doctors, lack of nutrition knowledge, lack of
      knowledge of causes of malnutrition and local culture food taboos. The status of
      child nutrition has been improved significantly since the intervention measure
      implementation. The change of prevalence of underweight children aged 6-17 months
      prior to and after the intervention was significant: 20.5% before and 13.7% after
      the intervention in infants aged 6-11 months, and 39.0% before and 26.4% after
      the intervention in young children aged 12-17 months. Prevalence of girls was
      higher than that of boys. Some women began to eat vegetables and pork from the
      market, which were forbidden by the culture food taboos. There is no case report
      of child thiamine deficiency in project villages. CONCLUSION: The prevalence of
      moderate and severe protein-energy malnutrition is high in Dai infants and young
      children. However, based on the local situation, participatory community-based
      comprehensive nutrition intervention effectively reduces the prevalence of child
      malnutrition and thiamine deficiency. It is highlighted that population
      nutritional intervention can produce better results with participation at a
      community level.

PMID- 17445057
TI  - Moderate-vigorous physical activity and body fatness in Chinese urban school
      children.
AB  - BACKGROUND: The exact relation between moderate-vigorous physical activity (MVPA)
      and body fatness in children has yet to be fully defined. This study examined the
      relationship between MVPA and body fatness in Chinese urban school children aged
      9-11 years, in an 8 month longitudinal study. METHODS: Two hundred and ten
      children (aged 9-11 years; 97 boys and 113 girls) were recruited from two public
      primary schools in the Beijing urban area. The baseline and the 8 month follow-up
      percent body fat (fat%), fat mass (FM), body mass index (BMI), waist size, hip
      size and the waist : hip ratio were investigated as measures of body fatness.
      Habitual MVPA level (activity-related energy expenditure, AEE) was measured using
      a validated self-report questionnaire recall. RESULTS: Nine-year-old girls who
      were in the top quartile for MVPA had significantly lower fat% than other girls
      at the same age (P < 0.05); 10-11-years girls who were in the top quartile for
      MVPA had significantly less increase in all of the indices of body fatness (P <
      0.05). There was no difference in fat% between the highly physically active (top
      quartile for MVPA) and less active 9-11 year boys in both cross-sectional and
      longitudinal statistical analyses. CONCLUSIONS: Highly physically active girls
      had lower fat% and less increase in body fatness. In light of world trends
      showing increasing childhood obesity, this study supports the hypothesis that
      MVPA might be effective in fighting excess body fat gain in Chinese school-age
      girls.

PMID- 17445058
TI  - Factors determining prenatal HIV testing for prevention of mother to child
      transmission in Dar Es Salaam, Tanzania.
AB  - BACKGROUND: The objectives of the study were (i) to evaluate the Prevention of
      Mother to Child Transmission (PMTCT) services in Temeke district, Tanzania and
      (ii) to identify factors for non-acceptance of HIV testing among pregnant mothers
      in the area. METHODS: A structured questionnaire was used in face-to-face
      interviews at five health centers in the district. Univariate and multiple
      logistic regression analyses were used to assess the association of the refusal
      of human immunodeficiency virus (HIV) testing with risk factors. RESULTS: Two
      hundred and seventy-three (68.1%) of the participants had already had HIV
      testing, while 128 (31.9%) had not. Participants' general knowledge of HIV was
      high, but specific knowledge of mother to child transmission (MTCT) was
      relatively low. In the multiple logistic regression analysis, frequencies of
      antenatal clinic visits, awareness of MTCT and intensive family support were
      significantly and inversely associated with the refusal of HIV testing.
      CONCLUSIONS: Frequency of antenatal care visits, spreading information on
      HIV/acquired immune deficiency syndrome especially MTCT, and husbands' intensive
      support are significant factors for increase of HIV test acceptance among
      pregnant women in the study area.

PMID- 17445059
TI  - Situational analysis of maternal and child health services for foreign residents
      in Japan.
AB  - BACKGROUND: Since the 1980s, the number of foreign residents in Japan has
      continuously been on the rise. In order to improve the foreign resident support
      services infrastructure and effectiveness, a survey was conducted at a national
      level from February to August 2002. The survey was done via a mailed
      questionnaire to all municipalities in Japan. METHODS: For the purpose of the
      study, municipalities were divided into four groups based on level of
      urbanization and numbers of foreign residents in the area. The situation of the
      foreign maternal and child support programs were compared and the municipal
      administrations were evaluated. In addition, the attribution analysis and
      evaluation of the foreigner support program was conducted in each municipality
      group. RESULTS: The evaluation of the current service support program for
      foreigner was not judged positively in the majority (95%) of the municipalities.
      In the non-urbanized municipalities with a low composition of foreigners, the
      foreigner mother and child support program were not functional compared with
      other regions. Additionally, various factors were highlighted based on
      attribution analysis among each group. Although most of the municipalities
      recognized the importance of the foreign resident support program, the
      evaluations showed a wide gap between intention and reality. CONCLUSION: It is
      recommended that the barriers as identified in the research results are
      rectified, and the current situation improved based on municipality
      characteristics, local demands and the needs of the population. The efficient use
      of limited fiscal and human resources is also advocated by strengthening of
      cooperation with other official bodies and also employing foreign residents to
      work in public offices for facilitating the foreign residents support programs.

PMID- 17445062
TI  - The origin of the 1 x 73-m2 body surface area normalization: problems and
      implications.
AB  - A historical review of the origins of body surface area (BSA) determination
      reveals a number of theoretical and methodological errors, as does the choice of
      1 x 73 m(2) as the normal BSA for humans. BSA normalization is justifiable for
      some physiological variables, e.g. glomerular filtration rate and cardiac output,
      but not all. However, other normalization indices, in particular extracellular
      volume, offer theoretical and practical advantages compared with BSA. While the
      choice of the figure 1 x 73 m(2) is essentially arbitrary, and inapplicable to
      modern Western populations, its retention as a permanent physiological constant
      is recommended, in order to permit international and historical comparisons.

PMID- 17445063
TI  - Scaling of lactate threshold by peak oxygen uptake and by fat-free mass 0 x 67.
AB  - The lactate threshold (LT) represents the onset of metabolic acidosis during
      cardiopulmonary exercise testing (CPET). It is measured as a O(2) in the units of
      ml min(-1). In order to make comparisons among subjects, LT is often scaled or
      normalized by O(2) peak resulting in the LT/O(2) peak ratio. Ratio variables have
      underlying assumptions. One assumption is that the relationship between the
      numerator and denominator is linear with a zero y-intercept. If the relationship
      has a positive y-intercept, then the ratio will decrease with increasing values
      of the scaling variable thereby penalizing subjects with larger values of the
      scaling variable. Our purpose was to examine the validity of scaling LT by O(2)
      peak and by fat-free mass raised to 0 x 67 power (FFM(0 x 67)) as dimensional
      analysis predicts that LT is proportional to FFM(0 x 67). Cycle ergometer CPET
      was administered to 204 healthy, sedentary subjects (103 males) to the limit of
      tolerance. Lactate threshold was estimated noninvasively using the V-slope
      technique. Fat-free mass was assessed by skinfolds. The relationship of LT versus
      O(2) peak was linear with a positive y-intercept for both sexes. Consequently,
      the LT/O(2) peak ratio decreased as O(2) peak increased for both sexes. The
      relationship of LT versus FFM(0 x 67)was linear with a zero y-intercept for both
      sexes. Consequently, the plot of the LT/FFM(0 x 67) ratio versus FFM resulted in
      a straight line with a slope of zero for both sexes. The results of this study
      support the conclusion that FFM(0 x 67), but not O(2) peak, is a valid scaling
      variable for LT.

PMID- 17445064
TI  - Duplex ultrasonography is an efficient diagnostic tool for the detection of
      moderate to severe internal carotid artery stenosis.
AB  - BACKGROUND: The aim of this prospective national multicentre study with 10
      participating university and county hospitals was to establish the diagnostic
      accuracy of carotid duplex sonography in the identification of >or=70% internal
      carotid artery (ICA) stenosis defined according to European Carotid Surgery Trial
      (ECST) criteria. METHODS: In 134 patients, aged 69 +/- 9 years, ICA stenoses were
      identified by routine carotid duplex ultrasonography, confirmed angiographically
      within 2 months, and graded according to ESCT criteria. The accuracy of carotid
      duplex to detect ICA stenosis >or=70% was assessed using receiver operating
      characteristic (ROC) analysis with carotid angiography as a reference. RESULTS:
      Measurement of peak systolic velocity in ICA (PSV(ICA)) identified ICA stenosis
      >or=70% with high diagnostic accuracy that was Doppler angle dependent resulting
      in different optimal PSV(ICA) cut points within the angle range 0 degrees -49
      degrees (1 x 7 m s(-1)) and 50 degrees -62 degrees (2 x 3 m s(-1)). The
      diagnostic discrimination was significantly better when narrow Doppler angles (0
      degrees -49 degrees ) were used (P<0 x 01) providing the sensitivity of 98 +/- 2%
      and specificity of 94 +/- 4%. DISCUSSION: Ultrasound duplex technique identifies
      moderate to severe (>or=70%) ICA stenoses (ECST criteria) with high degree of
      accuracy that can be further improved by the use of Doppler angle specific
      optimal PSV(ICA) cut points.

PMID- 17445065
TI  - Practical approach for estimation of subcutaneous and visceral adipose tissue.
AB  - OBJECTIVES: The first objective was to investigate the correlations between
      anthropometrical measurements and visceral adipose tissue (VAT) and subcutaneous
      adipose tissue (SAT) in two cohorts differing in age using magnetic resonance
      imaging (MRI) as reference. A second objective was to investigate the potential
      usage of abdominal diameters in practical estimation of adipose tissue
      compartments using these cohorts. METHODS: Measurements of body mass index, waist
      circumference, sagittal abdominal diameter (sagittal AD) and transverse abdominal
      diameter (transverse AD) were obtained from 336 volunteers of age 14-70 years.
      Manual measurements of VAT and SAT from single slice MRI at the L4-L5 level were
      used as reference. The abdominal diameters were measured from the MR images.
      Linear correlations between the anthropometrical measurements and the reference
      were studied. RESULTS: Sagittal AD showed the strongest correlation to VAT (r
      >or= 0 x 780, P<0 x 0001) and transverse AD was found to give information about
      the amount of SAT (r >or= 0 x 866, P<0 x 0001). The ellipse spanned by the
      sagittal AD and the transverse AD was strongly correlated to the total amount of
      adipose tissue (r >or= 0 x 962, P<0 x 0001). CONCLUSION: Strong correlations were
      found between sagittal and transverse abdominal diameters, assessed using MRI,
      and VAT and SAT, respectively. These results suggest the use of abdominal
      diameters in practical estimations of VAT and SAT depots.

PMID- 17445066
TI  - The effect of transcutaneous electrical nerve stimulation on local and distal
      cutaneous blood flow following a prolonged heat stimulus in healthy subjects.
AB  - The aim of this study was to investigate the effects of transcutaneous electrical
      nerve stimulation (TENS) on blood flow and skin temperature following an
      elevation of baseline blood flow using infrared preheating. A randomized
      controlled approach was used whereby 66 healthy human subjects (33 male, 33
      female) were allocated to one of three intervention groups (n=22 per group, equal
      male and female): Control, Low frequency TENS (4 Hz/200 micros), or High
      frequency TENS (110 Hz/200 micros). TENS was applied just below motor threshold
      over the median nerve of the right forearm for 15 min immediately following an
      infrared preheating. Cutaneous blood flow and skin temperature were recorded at 3
      min intervals from the forearm and fingertips during TENS and for 15 min
      following TENS. Analysis of data revealed no significant differences between High
      and Low frequency TENS for cutaneous blood flow or skin temperature at the
      forearm. A small and short lived increase in cutaneous blood flow at the index
      finger was observed on TENS groups compared with control when TENS was switched
      off. TENS reduced skin temperature when compared to control during the first 9
      min of the 15-min stimulation period at the middle finger but not at the index
      finger. It was concluded that the effects of high and low frequency TENS when
      applied below motor threshold produced changes in blood flow and skin temperature
      that were transient and small.

PMID- 17445067
TI  - Effects of cellular phone use on ear canal temperature measured by NTC
      thermistors.
AB  - The earlier studies using phantom models and human subjects concerning warming
      effects during cellular phone use have been controversial, partly because
      radiofrequency (RF) exposures have been variable. In this randomized, double
      blind, placebo-controlled crossover trial, 30 healthy subjects were submitted to
      900 MHz (2W) and 1800 MHz (1W) cellular phone RF exposure, and to sham exposure
      in separate study sessions. Temperature signals were recorded continuously in
      both ear canals before, during and after the 35-min RF exposure and the 35-min
      sham exposure sessions. Temperature was measured by using small-sized NTC
      thermistors placed in the ear canals through disposable ear plugs. The mean
      temperature changes were determined during a set cardiovascular autonomic
      function studies: during a 5-min controlled breathing test, during a 5-min
      spontaneous breathing test, during 7-min head-up tilting, 1-min before, during
      and after two consecutive Valsalva manoeuvres and during a deep breathing test.
      Temperatures in the exposed ear were significantly higher during RF exposures
      compared with sham exposure in both 900 and 1800 MHz studies with maximum
      differences of 1 x 2 +/- 0 x 5 degrees C (900 MHz exposure) and 1 x 3 +/- 0 x 7
      degrees C (1800 MHz exposure). Temperatures in the RF-exposed ear were also
      significantly higher during the postexposure period compared with post-sham
      exposure period with maximum differences of 0 x 6 +/- 0 x 3 degrees C for 900 MHz
      and 0 x 5 +/- 0 x 5 degrees C for 1800 MHz. The results of this study suggest
      that RF exposure to a cellular phone, either using 900 or 1800 MHz with their
      maximal allowed antenna powers, increases the temperature in the ear canal. The
      reason for the ear canal temperature rising is a consequence of mobile phone
      battery warming during maximal antenna power use. The earlier published articles
      do not indicate that temperature rising in the ear canal has any significant
      contribution from the RF fields emitted from mobile phones.

PMID- 17445068
TI  - Carotid intima-media thickness in HIV patients treated with antiretroviral
      therapy.
AB  - INTRODUCTION: Increased cardiovascular risk in HIV patients in antiretroviral
      therapy (ART) may be due to HIV infection, direct effect of ART or dyslipidaemia
      induced by ART. Our aim was to study the relative importance of HIV, ART and
      dyslipidaemia on atherosclerosis, assessed by the comparison of carotid artery
      intima-media thickness (IMT) in non-smoking HIV patients with high or low serum
      cholesterol levels as well as in healthy volunteers. METHODS: HIV patients in ART
      with normal cholesterol (<or=5 x 5 mmol l(-1); n=13) or high cholesterol (>or=6 x
      5 mmol l(-1); n=12) as well as healthy controls (n=14) were included. All were
      non-smokers and had never received medication for dyslipidaemia or hypertension.
      IMT was measured by ultrasonography. RESULTS: In HIV patients with normal
      cholesterol (<or=5 x 5 mmol l(-1)), in HIV patients with hypercholesterolaemia
      (>or=6 x 5 mmol l(-1)) and in controls (5 x 1 +/- 0 x 9 mmol l(-1)) IMT were 683
      +/- 119, 656 +/- 99 and 657 +/- 99 microm, respectively. Thus no difference in
      IMT was found between the three groups. IMT values did not differ between
      patients receiving and not receiving protease inhibitors (658 +/- 117 microm
      versus 687 +/- 97 microm, P>0 x 05). In HIV patients IMT correlated inversely
      with HDL cholesterol levels (r=-0 x 50; P=0 x 01), whereas no correlation was
      found with total cholesterol or LDL cholesterol. CONCLUSIONS: In non-smoking HIV
      patients receiving ART no sign of accelerated atherosclerosis was found as
      assessed by IMT even not in hypercholesterolaemic HIV patients. IMT correlated
      with HDL cholesterol but not with LDL cholesterol. Based on these observations,
      one could speculate whether selective lowering of LDL cholesterol will be
      successful in reducing cardiovascular risk in non-smoking HIV patients.

PMID- 17445069
TI  - Could hyperoxic ventilation impair oxygen delivery in septic patients?
AB  - OBJECTIVE: In critically ill patients, a decrease in whole body oxygen
      consumption under hyperoxia has been reported and this could be related to
      hyperoxia-induced arterial changes. We investigated changes in brachial artery
      circulation and tone during short-term hyperoxic ventilation in septic patients.
      DESIGN AND SETTING: Prospective clinical study in the intensive care unit of a
      university hospital. PATIENTS: Fourteen patients (severe sepsis n=3 and septic
      shock n=11) requiring mechanically controlled ventilation due to sepsis syndrome
      were investigated under stable clinical conditions. INTERVENTIONS: After a 20-min
      period of hyperoxic ventilation (inspired oxygen fraction = 100%), two
      dimensional images of brachial artery cross-sectional area and brachial blood
      flow velocities were recorded using conventional ultrasonography and pulsed
      Doppler simultaneously with invasive arterial pressure measurements. MEASUREMENTS
      AND MAIN RESULTS: Hyperoxia did not affect heart rate, but increased mean
      arterial pressure and decreased cross-sectional areas both at the end of diastole
      and at the end of systole. Haemodynamic study showed an increase in resistance
      index, and a decrease in distensibility and compliance coefficients. Furthermore,
      a decrease in brachial artery blood flow and arterial oxygen delivery was
      observed during hyperoxic exposure. CONCLUSIONS: Hyperoxia was paradoxically
      demonstrated to decrease oxygen delivery in upper limbs during septic shock.

PMID- 17445070
TI  - Synergistic effects of ethanol and hyperthermia on carotid artery
      vasoconstriction.
AB  - BACKGROUND: Heatstroke is a serious condition and clinical studies indicate that
      vascular stroke increases with excessive consumption of alcohol (ethanol). It was
      our objective to test the influence of ethanol on cerebral perfusion at normal
      and higher temperatures. METHODS: Recording of isometric tension in rabbit
      carotid artery strips in organ baths with different concentrations of ethanol at
      37 degrees C and during hyperthermia (39-43 degrees C) and scintigraphic cerebral
      imaging of a radioactive isotope in the control situation and during
      hyperthermia. RESULTS: Stepwise heating induced reproducible reversible graded
      contraction, proportional to temperature. At high concentrations (toxic levels),
      ethanol induced an increase in tension and heating potentiated these responses.
      Extracellular Mg(2+) potentiated both heat-induced contraction and ethanol
      induced contraction while extracellular Ca(2+) had no effect on these responses.
      During hyperthermia and ethanol scintigraphic isotope uptake was reduced in
      cortical and cerebellar regions. CONCLUSIONS: Carotid artery vasomotor tone is
      temperature dependent and heating induces vasoconstriction. Alcohol (ethanol) at
      37 degrees C elicited carotid artery contraction at high concentrations (toxic
      levels) but at any concentration during elevated temperature (39-43 degrees C).
      Ethanol potentiated the effect of hyperthermia-induced vasoconstriction and
      reduced cerebral perfusion as shown by radionuclide imaging. The synergistic
      effect of ethanol and hyperthermia may induce heat stroke and brain damage.

PMID- 17445071
TI  - Pulse wave velocity reference values in healthy adults aged 26-75 years.
AB  - The stiffening of arteries is associated with various cardiovascular diseases.
      Arterial stiffening can be studied utilizing arterial pulse wave velocity (PWV),
      but the absence of reliable reference values for PWV has limited its use in
      clinical practice. The aim of this study was to establish a range of reference
      values for PWV. PWV was examined by measuring the time difference of systolic
      pulse waves in arteries from the aortic arch to the popliteal artery using whole
      body impedance cardiography (ICG). The study population consisted of 799
      individuals (age range 25-76 years), 283 of whom had no evidence of
      cardiovascular disease, and a low burden of risk factors was selected to
      represent an apparently healthy population. In healthy study population, PWV was
      higher in males (8 x 9 +/- 1 x 8 m s(-1)) than females (8 x 1 +/- 2 x 0 m s(-1),
      P<0 x 001). Young males had lower PWV values than old males. Correspondingly,
      young females also had lower PWV values than old females. PWV was clearly
      associated with age, and PWV was higher in young and middle-aged males than in
      females. There was no statistically significant difference between old males and
      females in PWV. In conclusion, whole-body ICG provides a practical method for PWV
      measurement. Reference values can be useful in the clinical management of
      patients, especially in detecting early vascular disease or an increased risk of
      cardiovascular complications.

PMID- 17445072
TI  - Embryogenetics: gene control of the embryogenesis of the eye.
AB  - In recent years there have been significant advances in our knowledge and
      understanding of the genetic control of embryonic development. The aim of this
      paper is to review the current state of knowledge regarding genetic control of
      embryogenesis, the first stage of ocular development. Products of numerous genes
      participate in signaling, induction and control during the formation of the
      neural plate, groove and tube, key events leading to the development of the
      future eye.

PMID- 17445073
TI  - Ocular manifestations of natural canine monocytic ehrlichiosis (Ehrlichia canis):
      a retrospective study of 90 cases.
AB  - OBJECTIVE: To investigate the spectrum, prevalence and treatment response rate of
      ocular manifestations associated with natural canine monocytic ehrlichiosis (CME)
      due to Ehrlichia canis. METHODS: The medical records of 90 dogs that were
      admitted for primary ocular problems and reacted positive for E. canis serum
      antibodies were reviewed. All the dogs were treated with oral doxycycline. In 79
      dogs, a combination of systemic corticosteroids and/or topical anti-inflammatory,
      mydriatics/cycloplegics and antibacterial agents were applied. RESULTS: The dogs
      ranged from 0.5 to 15 years in age; 55 were male and 35 female. A total of 19
      breeds were represented. In the majority of dogs, ocular abnormalities were
      noticed in conjunction with other CME-induced clinical signs. In 30/90 dogs,
      ophthalmic signs were the sole presenting complaint. Unilateral (22/90, 24.5%)
      and bilateral (68/90, 75.5%) uveitis was the most common ophthalmic diagnosis and
      was classified as anterior, posterior or panuveitis in 58 (64.5%), 8 (8.9%) and
      24 (26.6%) of the dogs, respectively. Bilateral uveitis was significantly more
      common than unilateral uveitis (P < 0.0001), and anterior significantly more
      common than posterior uveitis (P < 0.0001) or panuveitis (P < 0.0001). In
      addition, corneal ulceration (12/90, 13.3%), necrotic scleritis (10/90, 11.1%),
      low tear production (8/90, 8.9%) and orbital cellulitis (3/90, 3.3%) were seen.
      Of the 45 (50%) dogs with a satisfactory follow-up, 25 (55.5%), 11 (24.5%), and 9
      (20%) showed complete, partial and poor response to treatment, respectively. The
      number of dogs exhibiting complete resolution of the ocular manifestations was
      significantly higher than those with partial (P < 0.0001) or poor (P < 0.0001)
      response. CONCLUSIONS: CME should be considered a major differential for a wide
      range of ocular manifestations exhibited by dogs residing in the endemic areas of
      the disease. Anterior bilateral uveitis appears to be the most prevalent ocular
      lesion and a favorable outcome to systemic and topical treatment may be expected
      in the majority of the affected dogs.

PMID- 17445074
TI  - Schirmer tear test, phenol red thread tear test, eye blink frequency and corneal
      sensitivity in the guinea pig.
AB  - OBJECTIVE: To establish reference values for Schirmer tear tests (STT) I and II,
      phenol red thread (PRT) tear test and eye blink frequency, and to determine
      corneal sensitivity for normal guinea pigs. ANIMALS STUDIED: One hundred and
      eight eyes of 54 adult Duncan-Hartley guinea pigs. PROCEDURE: Schirmer tear test
      (STT) I and then STT II were performed in 36 guinea pigs. PRT and STT I were
      compared in 18 adult Duncan-Hartley guinea pigs. Corneal sensitivity was
      determined in 23 guinea pigs by evaluating the corneal touch threshold (CTT) of
      five different regions using a Cochet-Bonnet esthesiometer. Eye blink frequency
      was measured in 10 guinea pigs over a period of 20 min and in 17 guinea pigs over
      a period of 10 min. RESULTS: Mean STT I was 0.36 mm +/- 1.09 mm (wetting/min) and
      mean STT II was 0.43 mm +/- 1.29 mm (wetting/min). There was no significant
      difference between mean STT I and mean STT II (P = 0.79). The mean PRT-value was
      16 +/- 4.7 mm (wetting/15 s), and the mean STT I-value in the same guinea pigs
      was 0.6 +/- 1.83 mm (wetting/min). Corneal sensitivity was significantly higher
      in the center than in the four limbal regions. The mean CTT for central, ventral,
      nasal, temporal and dorsal regions was 2, 1.7, 1.7, 1.7 and 1.6 cm or 3.7, 5.2,
      5.6, 5.7 and 6.4 g/mm(2), respectively. Eye blink frequency was between two to
      five (mean 3.4 +/- 1.04) blinks per eye over 20 min in guinea pigs in their home
      environment, while in handheld and restrained guinea pigs eye blink frequency
      showed a variation between 0 and 17 blinks per eye (mean 3.24 +/- 3.64 blinks per
      eye) over 10 min. CONCLUSIONS: As there were no significant differences between
      STT I and STT II results, reflex tear secretion in the guinea pig may not exist.
      The most likely explanation is a lower corneal sensitivity in the guinea pig than
      in other species, such as cats, dogs and horses. Because of the small amount of
      tears, PRT is the preferred test for tear measurement in the guinea pig.

PMID- 17445075
TI  - Corneal sensitivity and aqueous tear production in dogs undergoing evisceration
      with intraocular prosthesis placement.
AB  - OBJECTIVE: To determine whether there is an association between evisceration with
      intraocular prosthesis placement via a dorsal scleral approach and decreased
      corneal sensitivity or aqueous tear production in dogs. DESIGN: Prospective
      study. PROCEDURE: Twenty-one dogs scheduled to undergo unilateral evisceration
      with intraocular prosthesis, and with a normal normotensive contralateral eye,
      based on slit-lamp biomicroscopy, indirect ophthalmoscopy and applanation
      tonometry, were included in the study. Central corneal sensitivity was measured
      with a Cochet-Bonnet esthesiometer prior to (week 0) and 2, 7, 14 and 28 weeks
      following surgery. Other pre- and postoperative data collected were Schirmer's
      tear test (STT I), Schirmer's tear test with topical anesthesia (STT II), corneal
      fluorescein retention, and intraocular pressure (IOP; postoperative control eye
      only). Axial globe length was determined for both eyes. Scleral incision length
      in the surgery eye was also recorded. RESULTS: Corneal sensitivity was
      significantly lower in eyes undergoing evisceration with intraocular prosthesis
      than in control eyes both preoperatively and postoperatively at all time points.
      There was no significant difference between preoperative and postoperative
      corneal sensitivity within the two groups. There was no significant difference in
      STT I or STT II-values between control eyes and surgery eyes preoperatively.
      There was a significant difference between preoperative and 2-week postoperative
      STT I in the surgery eye. There was a significant difference between the
      preoperative and 28-week postoperative STT II in the surgery eye. The 28-week
      postoperative STT I-values differed significantly between control and surgery
      eyes. Corneal sensitivity tended to decrease with increased degree of buphthalmos
      or with increased scleral incision length, although neither relationship was
      statistically significant. CONCLUSIONS: Eyes that have sustained chronically
      elevated intraocular pressure had decreased axial corneal sensitivity compared to
      normal eyes, which persisted even after intraocular pressure was reduced. The
      presence of buphthalmos appeared to be a factor in globes developing decreased
      corneal sensitivity. Evisceration via a dorsal scleral incision did not result in
      a significant further reduction in axial corneal sensitivity. A mild reduction in
      aqueous tear production occurred over time in globes following evisceration with
      intraocular prosthesis.

PMID- 17445076
TI  - Circadian rhythm of intraocular pressure in cats.
AB  - OBJECTIVE: To evaluate the rhythm of intraocular pressure (IOP) in healthy
      domestic cats with no evidence of ocular disease and to analyze the influence of
      photoperiod, age, gender and ocular diseases on diurnal-nocturnal variations of
      cat IOP. ANIMALS: All animals were Domestic Short-haired cats; 30 were without
      systemic or ocular diseases, classified as follows: 12 male intact adult cats,
      five intact adult female, five adult spayed female, and eight male cats; the
      latter were less than 1 year of age. In addition, five adult cats with uveitis
      and three adult cats with secondary glaucoma were included. PROCEDURE: IOP was
      assessed with a Tono-Pen XL at 3-h intervals over a 24-h period in 12 healthy
      adult male cats kept under a photoperiod of 12-h light/12-h darkness for 2 weeks.
      Eight animals from the same group were then kept under constant darkness for 48
      h, and IOP was measured at 3-h intervals for the following 24 h. In addition, IOP
      was assessed at 3 p.m. and 9 p.m. in five intact females, five spayed females,
      and in eight young cats, as well as in five adult cats with uveitis and three
      glaucomatous cats. RESULTS: Consistent, daily variations in IOP were observed in
      animals exposed to a light-dark cycle, with maximal values during the night. In
      cats exposed to constant darkness, maximal values of IOP were observed at
      subjective night. Differences of IOP values between 3 p.m. and 9 p.m. (diurnal
      nocturnal variations) persisted in intact females, spayed females, and young
      animals, as well as in uveitic and glaucomatous eyes. CONCLUSIONS: The present
      results indicate a daily rhythm of cat IOP, which appears to persist in constant
      darkness, suggesting some level of endogenous circadian control. In addition,
      daily variations of cat IOP seem to be independent of gender, age, or ocular
      diseases (particularly uveitis and glaucoma).

PMID- 17445077
TI  - Grid keratotomy as a treatment for superficial nonhealing corneal ulcers in 10
      horses.
AB  - OBJECTIVE: To describe the clinical symptoms of 10 cases of superficial
      nonhealing corneal ulcers in horses and to evaluate the results of grid
      keratotomy in these patients. DESIGN: Retrospective study. ANIMALS: Ten horses
      with superficial nonhealing corneal ulceration in one eye. PROCEDURE: The
      signalment, history and clinical symptoms are reported of 10 patients with
      superficial nonhealing corneal ulcers during the period from August 2003 to
      February 2005. Grid keratotomy was performed in all cases. In addition, the
      surgical procedure of grid keratotomy and response to therapy are described.
      RESULTS: Horses generally responded well to grid keratotomy (eight cases healed
      after one grid keratotomy and one horse healed after a second grid keratotomy;
      one case was not available for follow-up). Only 2/10 had discomfort after
      treatment and only 2/9 had some degree of scarring after treatment. The healing
      time, which was known in seven cases, averaged 8.4 days (+/- SD 4). CONCLUSIONS
      AND CLINICAL RELEVANCE: Grid keratotomy is an appropriate option for treatment of
      superficial nonhealing corneal ulcers in horses. The procedure is simple to
      perform. It generally induces a rapid and uncomplicated healing of the cornea.
      Only in a limited number of cases does a small amount of scarring occur.

PMID- 17445078
TI  - Immunohistochemical investigation of canine episcleritis.
AB  - OBJECTIVES: To identify macrophages, B cells and T cells in archived canine
      episcleral biopsies and to correlate these findings with the clinical
      presentation and therapeutic outcome. PROCEDURES: Archived formalin-fixed
      biopsies were immunohistochemically labeled for CD18, CD79a, and CD3 to identify
      macrophages, B cells and T cells, respectively. Slides were digitally
      photographed and positive cells were manually counted. Signalment, duration of
      illness, affected eye(s), treatment, and therapeutic outcome were reviewed for
      each dog. Dogs were divided into groups based on clinical presentation
      (unilateral episcleritis, bilateral episcleritis or nodular granulomatous
      episclerokeratitis (NGE). RESULTS: Twenty-four cases were evaluated. There were
      19 episcleritis (13 unilateral, six bilateral) and five NGE cases. The mean age
      for clinical manifestations of unilateral episcleritis was 6.8 years, bilateral
      episcleritis was 8.7 years, and NGE was 3.8 years. The Cocker Spaniel was over
      represented in the episcleritis groups. All NGE cases were Collies. Approximately
      50% of the unilateral episcleritis cases resolved and did not require long-term
      therapy. Almost all cases of bilateral episcleritis and NGE required continuous
      medical therapy to maintain remission. There was a significantly higher
      percentage of B lymphocytes in biopsies from lesions that required ongoing
      medical therapy to maintain lesion remission than in the lesions that resolved,
      and for which medications were discontinued (P = 0.0471). CONCLUSIONS: The
      prognosis for resolution of NGE and bilateral episcleritis without long-term
      medical therapy is poor. There is a significant difference in the inflammatory
      cell population in episcleritis that resolved with medical therapy vs.
      episcleritis that required ongoing medical therapy.

PMID- 17445079
TI  - Assessment of the posterior segment of the cat eye by optical coherence
      tomography (OCT).
AB  - OBJECTIVES: To assess the feasibility of optical coherence tomography (OCT) for
      examining the cat ocular fundus, to provide normative data on retinal thickness
      in different fundus regions, and to demonstrate selected surgically induced
      vitreoretinal pathologies in the cat. ANIMAL STUDIED: Forty-five eyes of 28
      healthy domestic cats and two eyes of domestic cats that had undergone subretinal
      implantation surgery for a visual prosthesis were examined. PROCEDURES: An
      optical coherence tomograph (Zeiss-Humphrey) was used to examine the anesthetized
      animals. At least five vertical and five horizontal scans in regular distribution
      were recorded for each cat including (1) the peripapillary region, (2) the area
      centralis, and (3) the peripheral retina. Thickness was measured manually at five
      locations in each scan. Retinal thickness was compared in the three above
      mentioned fundus regions, between eyes and between vertical and horizontal scans.
      OCT was additionally performed in animals with retinal detachment and a
      subretinal visual prosthesis. RESULTS: OCT measurements required only minimal
      adjustments of human settings and yielded high quality images. In comparison to
      humans intraretinal layers were more difficult to differentiate. Retinal
      thickness was highest in the peripapillary region (245 +/- 21 microm), followed
      by the peripheral retina (204 +/- 11 microm) and the area centralis (182 +/- 11
      microm; all P < 0.0001). There was no statistically significant difference
      between right and left eye or between vertical and horizontal scans. OCT
      demonstrated retinal detachment, an iatrogenic break and a subretinal prosthetic
      device in high detail. CONCLUSIONS: Retinal thickness was measurable with high
      precision; values compare well to older histologic studies. OCT bears significant
      advantages over histology in enabling one to repeat measurements in living
      animals and thus allowing longitudinal studies. Various vitreoretinal pathologies
      common in feline eyes are detectable and quantifiable by OCT.

PMID- 17445080
TI  - Canine ocular histiocytic sarcoma.
AB  - OBJECTIVE: To describe and characterize histiocytic sarcoma (HS) first detected
      in the eyes of dogs using the large database at the comparative ocular pathology
      laboratory of Wisconsin (COPLOW). METHODS: Cases diagnosed as HS were selected
      from the COPLOW database. Slides were reviewed to describe the cellular
      morphology, localize the tumor within the globe, record the tumor distribution
      and measure the size of the tumor. Further sections were taken to perform
      immunohistochemistry for Melan-A, CD18 and S-100, and for ferric iron staining.
      The following clinical information was recorded: breed, age, gender, laterality,
      clinical signs upon presentation and follow-up information obtained by response
      to a mailed survey and phone contact. RESULTS: Twenty-six cases were confirmed as
      being HS according to the immunohistochemical results (CD18 positive and Melan-A
      negative). The most prevalent breed was Rottweiler (eight cases), followed by
      Retriever breeds (seven Golden Retrievers and five Labrador Retrievers). The mean
      age was 8.61 +/- 2.43 years. There were three intact male, eight castrated male,
      one intact female and 14 spayed female dogs. In 15 dogs there were no concurrent
      systemic clinical signs at the time of diagnosis. Sixteen of 19 dogs with follow
      up information available died as a result of causes related to the tumor,
      although only three of them received a necropsy. Survival time varied between 5
      days and 6 months after enucleation. Three of the dogs were alive at the time the
      information was gathered. Mean tumor surface was 0.613 +/- 0.38 cm(2). S-100 was
      diffusely positive in 10 cases, isolated positive cells were found in 11 cases
      and five cases were completely negative. Seven of the cases were positive for
      ferric iron. CONCLUSIONS: Histiocytic sarcoma must be considered in the
      differential diagnosis of dogs with intraocular masses, especially in Rottweilers
      and Retriever breeds. Because it carries poor prognosis, it must be distinguished
      from melanoma. A good discriminator for this purpose in paraffin-embedded tissues
      is finding CD18-positive cells and no reactivity against Melan-A. S-100 and
      ferric iron staining does not seem to be useful. Ocular HS is considered to be a
      manifestation of a systemic disease even when the disease is first recognized in
      the eye.

PMID- 17445081
TI  - Evaluation of the clinical efficacy of subconjunctival injection of clindamycin
      in the treatment of naturally occurring infectious bovine keratoconjunctivitis.
AB  - OBJECTIVE: To determine the clinical efficacy of subconjunctival injection of
      clindamycin in the treatment of naturally occurring infectious bovine
      keratoconjunctivitis (IBK). ANIMALS STUDIED: Clinically, out of 81 animals
      examined, 46 were found to be suffering from IBK of variable severity. The ocular
      secretions were collected and cultured for Moraxella bovis. The study included 36
      Holstein cattle from which M. Bovis was isolated. These animals ranged between 4
      and 28 months of age. PROCEDURES: The severity of the clinical findings were
      scored as normal, mild, moderate, and severe. Clindamycin was injected
      subconjunctivally at a total dose of 150 mg (1 mL), once daily for 3 days to the
      test group (n = 18); isotonic saline solution (1 mL) was administered to the
      control group. After treatment, all cattle were re-examined and clinical response
      was evaluated on days 3, 7 and 15 post-treatment. RESULTS: Compared with the
      control group and prior to treatment, all active lesions such as blepharospasm,
      epiphora, photophobia, chemosis, corneal edema, and corneal ulceration were
      generally resolved by day 15 after subconjunctival injection of clindamycin.
      Severity of IBK lesions increased on days 3 and 7, compared to baseline in the
      control group administered isotonic saline solution. CONCLUSIONS: The results of
      this study suggest that subconjunctival injection of clindamycin is effective in
      the treatment of naturally occurring infectious bovine keratoconjunctivitis.

PMID- 17445082
TI  - Shope fibroma virus keratitis and spontaneous cataracts in a domestic rabbit.
AB  - A 7-year-old domestic rabbit presented for an enlarging ventral perilimbal mass
      OS. Keratectomy was performed to remove the mass. A diagnosis of Shope fibroma
      virus keratitis was confirmed based on signalment, clinical signs, histologic
      evaluation and virus isolation. Progression of bilateral cataracts leading to
      visual deficits was addressed with phacoemulsification. The rabbit remained
      visual and comfortable 5 months postoperatively and free of recurrence of the
      limbal mass 9 months after initial presentation.

PMID- 17445083
TI  - Acute blindness in a dog caused by an explosive blast.
AB  - A 3-year-old, intact male, mixed breed dog was presented with a complaint of
      acute blindness. Ten days previously, the area where the dog was walking came
      under a rocket attack, and a rocket landed and exploded 300 meters away from the
      dog. Physical examination was unremarkable. Ophthalmoscopic examination revealed
      posterior segment fibrin clots and extensive vitreal hemorrhage in the right eye.
      A total retinal detachment (360 degrees retinal dialysis) with no evidence of
      hemorrhage was noted in the left eye. There was no sign of any penetrating ocular
      trauma, and it was assumed that the posterior segment findings were primary
      injuries caused by the blast wave itself. Following anti-inflammatory treatment,
      partial vision was restored in the right eye. Surgical re-attachment of the
      retina was discussed and declined by the owner. This report describes, for the
      first time, vitreal hemorrhage and retinal detachment as the sole injuries caused
      by an explosive blast wave.

PMID- 17445084
TI  - Tolvaptan, an orally active vasopressin V(2)-receptor antagonist - pharmacology
      and clinical trials.
AB  - Tolvaptan is an orally effective nonpeptide arginine vasopressin (AVP) V(2)
      receptor antagonist synthesized by Otsuka Pharmaceutical Co., Ltd. In in vitro
      receptor-binding studies, tolvaptan blocked the binding of [(3)H]AVP to human
      V(2) receptors with 29-fold greater selectivity than that for V(1a) receptors,
      and showed no inhibition of V(1b) receptors. Tolvaptan inhibited not only the
      binding of [(3)H]AVP but also the AVP-induced production of cyclic AMP in human
      V(2)-receptor-expressing HeLa cells. In addition, tolvaptan has no intrinsic V(2)
      receptor agonistic effect. In in vivo studies, tolvaptan showed marked aquaresis
      in healthy and diseased animals. In rat models with acute and chronic
      hyponatremia, tolvaptan improved hyponatremia, resulting in the prevention of
      death, and improved organ water retention. Tolvaptan reduced cardiac preload
      without unfavorable effects on renal functions, systemic hemodynamics, or
      circulating neurohormones in dogs with heart failure (HF). Furthermore, in animal
      models of human polycystic kidney disease (PKD), tolvaptan showed a decrease in
      kidney weight as well as in cyst and fibrosis volume. In clinical trials
      including the "ACTIV in CHF" study, tolvaptan in addition to standard therapy
      increased fluid loss resulting in decreased body weight, and improved edema and
      serum sodium without affecting blood pressure, heart rate, or renal functions in
      patients with HF. In patients with hyponatremia, treatment with tolvaptan without
      fluid restriction appeared to be more effective than fluid restriction alone at
      correcting hyponatremia without an increase in adverse events. A phase III trial
      EVEREST is currently being conducted to evaluate the long-term efficacy and
      safety of tolvaptan in hospitalized patients with severe HF. In conclusion,
      tolvaptan offers the possibility of a useful therapy in hyponatremia, congestive
      heart failure, and various other diseases that are associated with volume
      overload. Furthermore, tolvaptan is also expected to be effective in the
      treatment of PKD.

PMID- 17445085
TI  - Therapeutic potential of H11 kinase for the ischemic heart.
AB  - H11 kinase (H11K) is a small heat shock protein expressed predominantly in the
      heart and skeletal muscle, which plays a critical role in the maintenance of
      cardiac cell survival and in promoting cell growth through the activation of
      complementary signaling pathways. An overexpression of H11K was detected in
      various forms of heart disease, both in animal models and in patients, including
      acute and chronic ventricular dysfunction, and myocardial hypertrophy.
      Overexpression of H11K was reproduced in a cardiac-specific transgenic model,
      which led to significant progress in understanding the role and mechanism of
      action of the protein. Increased expression of H11K confers a cardioprotection
      that is equivalent to ischemic preconditioning; it promotes cardiac hypertrophy
      while maintaining contractile function. The overexpression of H11K is sufficient
      to activate most of the signaling pathways involved in cardiac cell growth and
      survival, including the phosphatidylinositol-3-kinase/Akt pathway, the AMP
      dependent protein kinase, the PKCepsilon pathway of ischemic preconditioning, the
      nitric oxide pathway of delayed cardioprotection, and the mTOR pathway of cell
      growth. As a result, the survival response triggered by H11K in the heart
      includes antiapoptosis, cytoprotection, preconditioning, growth, and metabolic
      stimulation. In addition to activating signaling pathways, H11K promotes the
      subcellular translocation and crosstalk of intracellular messengers. This review
      discusses the biological function of H11K, its molecular mechanisms of action,
      and its potential therapeutic relevance. In particular, we discuss how preemptive
      conditioning of the heart by H11K might be beneficial for patients with ischemic
      heart disease who would be at risk of further irreversible cardiac damage.

PMID- 17445086
TI  - Nitric oxide-independent stimulation of soluble guanylate cyclase with BAY 41
      2272 in cardiovascular disease.
AB  - The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic 3',5'-guanosine
      monophosphate (cGMP) pathway plays an important role in cardiovascular regulation
      by promoting vasodilation and inhibiting vascular smooth muscle cell growth,
      platelet aggregation, and leukocyte adhesion. In pathophysiological states with
      endothelial dysfunction this signaling pathway is impaired. Activation of sGC has
      traditionally been achieved with nitrovasodilators; however, these drugs are
      associated with the development of tolerance and potentially deleterious cGMP
      independent actions. In this review the actions of BAY 41-2272, the prototype of
      a new class of NO-independent sGC stimulators, in cardiovascular disease models
      is discussed. BAY 41-2272 binds to a regulatory site on the alpha-subunit of sGC
      and stimulates the enzyme synergistically with NO. BAY 41-2272 had
      antihypertensive actions and attenuated remodeling in models of systemic arterial
      hypertension. It also unloaded the heart in experimental congestive heart
      failure. BAY 41-2272 reduced pulmonary vascular resistance in acute and chronic
      experimental pulmonary arterial hypertension. Furthermore, BAY 41-2272 inhibited
      platelet aggregation in vitro and leukocyte adhesion in vivo. These findings make
      direct sGC stimulation with BAY 41-2272 a promising new therapeutic strategy for
      cardiovascular diseases and warrant further studies. Finally, the significance of
      the novel NO- and heme-independent sGC activator BAY 58-2667, which activates two
      forms of NO-insensitive sGC, is briefly discussed.

PMID- 17445087
TI  - Oleamide: a fatty acid amide signaling molecule in the cardiovascular system?
AB  - Oleamide (cis-9,10-octadecenoamide), a fatty acid primary amide discovered in the
      cerebrospinal fluid of sleep-deprived cats, has a variety of actions that give it
      potential as a signaling molecule, although these actions have not been
      extensively investigated in the cardiovascular system. The synthetic pathway
      probably involves synthesis of oleoylglycine and then conversion to oleamide by
      peptidylglycine alpha-amidating monooxygenase (PAM); breakdown of oleamide is by
      fatty acid amide hydrolase (FAAH). Oleamide interacts with voltage-gated Na(+)
      channels and allosterically with GABA(A) and 5-HT(7) receptors as well as having
      cannabinoid-like actions. The latter have been suggested to be due to
      potentiation of the effects of endocannabinoids such as anandamide by inhibiting
      FAAH-mediated hydrolysis. This might underlie an "entourage effect" whereby co
      released endogenous nonagonist congeners of endocannabinoids protect the active
      molecule from hydrolysis by FAAH. However, oleamide has direct agonist actions at
      CB(1) cannabinoid receptors and also activates the TRPV1 vanilloid receptor.
      Other actions include inhibition of gap-junctional communication, and this might
      give oleamide a role in myocardial development. Many of these actions are absent
      from the trans isomer of 9,10-octadecenoamide. One of the most potent actions of
      oleamide is vasodilation. In rat small mesenteric artery the response does not
      involve CB(1) cannabinoid receptors but another pertussis toxin-sensitive, G
      protein-coupled receptor, as yet unidentified. This receptor is sensitive to
      rimonabant and O-1918, an antagonist at the putative "abnormal-cannabidiol" or
      endothelial "anandamide" receptors. Vasodilation is mediated by endothelium
      derived nitric oxide, endothelium-dependent hyperpolarization, and also through
      activation of TRPV1 receptors. A physiological role for oleamide in the heart and
      circulation has yet to be demonstrated, as has production by cells of the
      cardiovascular system, but this molecule has a range of actions that could give
      it considerable modulatory power.

PMID- 17445088
TI  - N-(p-amylcinnamoyl)anthranilic acid (ACA): a phospholipase A(2) inhibitor and TRP
      channel blocker.
AB  - Phospholipase A(2) enzymes display a superfamily of structurally different
      enzymes classified in at least nine subfamilies by biochemical and structural
      properties. N-(p-amylcinnamoyl)anthranilic acid commonly referred to as ACA is
      often used as a broad-spectrum inhibitor for the characterization of
      phospholipase A(2)-mediated pathways. Compounds like ACA and ACA-like structures
      have been described to block the receptor-induced release of arachidonic acid and
      subsequent signaling cascades in the pancreas and the cardiovascular system. We
      showed that ACA directly blocks several transient receptor potential (TRP)
      channels (TRPC6, TRPM2, TRP and TRPM8). With respect to the published data of ACA
      in the phospholipase A(2) field, the finding that ACA blocks diacylglycerol
      activated TRP channels is of specific interest as it offers the opportunity to
      interfere with receptor-induced calcium-dependent signaling processes in
      platelets and vascular smooth muscle cells. Overall, N-phenylcinnamides, as a new
      pharmaceutical lead structure, form the first class of synthetic TRP channel
      blockers and represent a promising start for the development of small organic TRP
      channel-specific blockers.

PMID- 17445089
TI  - Perhexiline.
AB  - Perhexiline, 2-(2,2-dicyclohexylethyl)piperidine, was originally developed as an
      anti-anginal drug in the 1970s. Despite its success, its use diminished due to
      the occurrence of poorly understood side effects including neurotoxicity and
      hepatotoxicity in a small proportion of patients. Recently, perhexiline's
      mechanism of action and the molecular basis of its toxicity have been elucidated.
      Perhexiline reduces fatty acid metabolism through the inhibition of carnitine
      palmitoyltransferase, the enzyme responsible for mitochondrial uptake of long
      chain fatty acids. The corresponding shift to greater carbohydrate utilization
      increases myocardial efficiency (work done per unit oxygen consumption) and this
      oxygen-sparing effect explains its antianginal efficacy. Perhexiline's side
      effects are attributable to high plasma concentrations occurring with standard
      doses in patients with impaired metabolism due to CYP2D6 mutations. Accordingly,
      dose modification in these poorly metabolizing patients identified through
      therapeutic plasma monitoring can eliminate any significant side effects. Herein
      we detail perhexiline's pharmacology with particular emphasis on its mechanism of
      action and its side effects. We discuss how therapeutic plasma monitoring has led
      to perhexiline's safe reintroduction into clinical practice and how recent
      clinical data attesting to its safety and remarkable efficacy led to a
      renaissance in its use in both refractory angina and chronic heart failure.
      Finally, we discuss the application of pharmacogenetics in combination with
      therapeutic plasma monitoring to potentially broaden perhexiline's use in heart
      failure, aortic stenosis, and other cardiac conditions.

PMID- 17445090
TI  - The intrinsic enzymatic activity of procarboxypeptidase U (TAFI) does not
      significantly influence the fibrinolytic rate: reply to a rebuttal.

PMID- 17445091
TI  - Non-hematopoietic EPCR regulates the coagulation and inflammatory responses
      during endotoxemia.
AB  - BACKGROUND: Activated protein C (APC) protects the host from severe sepsis.
      Endothelial protein C receptor (EPCR) is expressed on both hematopoietic
      leukocytes and non-hematopoietic endothelium, and plays a key role in protein C
      activation. OBJECTIVES: We explore the influence of EPCR deletion on the
      responses to lipopolysaccharide (LPS) and then determine whether the observed
      differences are due to loss of hematopoietic or non-hematopoietic EPCR. METHODS
      AND RESULTS: After LPS challenge, EPCR null (Procr(-/-)) mice exhibited more
      thrombin and cytokine generation, neutrophil sequestration in the lung and a
      higher mortality rate than Procr(+/-) mice. Procr(+/-) BM/Procr(-/-) (non
      hematopoietic Procr(-/-)) and Procr(-/-) BM/Procr(+/-) (hematopoietic Procr(-/-))
      chimeric mice were generated by bone marrow (BM) transplantation. Compared with
      control Procr(+/-) mice, non-hematopoietic Procr(-/-) mice exhibited reduced
      protein C activation by thrombin and exaggerated responses to LPS challenge,
      whereas Procr(+/-) mice and hematopoietic Procr(-/-) mice exhibited similar
      protein C activation by thrombin and similar responses to LPS challenge.
      CONCLUSIONS: EPCR deletion exaggerates the host responses to LPS primarily due to
      deficiency of EPCR on the non-hematopoietic cells.

PMID- 17445092
TI  - Factor VIII (FVIII) gene mutations in 120 patients with hemophilia A: detection
      of 26 novel mutations and correlation with FVIII inhibitor development.
AB  - BACKGROUND: As the publication of the sequence of the factor VIII gene (FVIII) in
      1984, a large number of mutations that cause hemophilia A (HA) have been
      identified. Thanks to the advances in the detection of mutations, it is now
      possible to identify a putative FVIII sequence alteration in the vast majority of
      patients with HA. OBJECTIVES: Our main objective was to report on the spectrum of
      FVIII mutations and their distribution throughout the gene in 120 patients with
      HA. METHODS: Screening of FVIII mutations was performed using direct sequencing.
      Newly described missense mutations were further studied by molecular modeling.
      RESULTS: A total of 47 different HA causative FVIII mutations have been
      identified, 26 of which are described for the first time. These novel mutations
      include 14 missense and six nonsense mutations, two small deletions, one large
      deletion and three splice-site mutations. We further investigated the development
      of FVIII-specific inhibitors in all patients with HA. We found that four novel
      mutations (Ser882X, Tyr1786Ser, Ala2218Thr and a splice-site defect in intron 22)
      were associated with inhibitor development. CONCLUSION: These data extend our
      insight into the mechanisms by which novel amino acid substitutions may lead to
      HA, and how HA patient genotypes influence the risk of FVIII inhibitor
      development.

PMID- 17445093
TI  - Controlled shedding of platelet glycoprotein (GP)VI and GPIb-IX-V by ADAM family
      metalloproteinases.
AB  - BACKGROUND: Platelet glycoprotein (GP)VI that binds collagen, and GPIb-IX-V that
      binds von Willebrand factor, initiate thrombus formation. OBJECTIVES: In this
      study, we investigated the mechanisms of metalloproteinase-mediated ectodomain
      shedding that regulate the surface expression of GPVI, GPIbalpha (the major
      ligand-binding subunit) and GPV (that regulates thrombin-dependent activation via
      GPIbalpha). METHODS AND RESULTS: Immunoblotting human platelet lysates using
      affinity-purified antibodies against cytoplasmic domains of GPVI, GPIbalpha or
      GPV allowed simultaneous analysis of intact and cleaved receptor, and revealed
      (i) that a significant fraction of GPIbalpha, but not GPVI, exists in a cleaved
      state on platelets, even when isolated in the presence of metalloproteinase
      inhibitor (GM6001) or EDTA; (ii) the same-sized membrane-associated fragments of
      GPVI or GPIbalpha are generated by phorbol-ester (PMA), the mitochondrial
      targeting reagent CCCP, the calmodulin inhibitor W7, or the thiol-modifying
      reagent, N-ethylmaleimide, that directly activates ADAM10/ADAM17; and (iii) GPV
      is shed by both metalloproteinase- and thrombin-dependent mechanisms, depending
      on the concentration of thrombin. Based on the predicted cleavage area defined by
      these studies, ADAM10, but not ADAM17, cleaved a GPVI-based synthetic peptide
      within the extracellular membrane-proximal sequence (PAR;Q(243)YY) as analyzed by
      MALDI-TOF-MS. In contrast, ADAM17, but not ADAM10, cleaved within the GPIbalpha
      based peptide (LRG;V(465)LQ). Both ADAM10 and ADAM17 cleaved within a GPV-based
      peptide (AQP;V(494)TT). Metalloproteinase-mediated shedding of GPIbalpha from
      GPIb-IX-transfected or GPVI-transfected cells induced by W7 or N-ethylmaleimide
      was inhibited by mutagenesis of sequences identified from peptide analysis.
      CONCLUSIONS: These findings suggest surface levels of GPVI, GPIbalpha and GPV may
      be controlled by distinct mechanisms involving ADAM10 and/or ADAM17.

PMID- 17445096
TI  - Satisfaction with current migraine therapy: experience from 3 centers in US and
      Sweden.
AB  - OBJECTIVE: To assess the level of satisfaction and determinants of satisfaction
      or dissatisfaction of patients presenting in tertiary care, in regard to their
      usual care (UC) for the acute treatment of migraine. DESIGN/METHODS: Patients
      seen in 3 headache centers were assessed by means of 21 attributes related to
      their UC. Questions covered satisfaction with efficacy (including onset of
      relief, degree of relief, consistency of action, ease of use), tolerability (lack
      of side effects overall, CNS side effects, other side effects), and willingness
      to continue using the same medication and to change to another medication. All
      questions were answered on a 5-point scale (where 1 was strongly agree, 2 was
      agree, 3 was neutral, 4 was disagree, and 5 was strongly disagree). RESULTS: We
      assessed 183 subjects (74.8% women, mean age = 39.3 years). UC consisted, as a
      single drug or combination, of: triptan conventional tablets--62%; triptan
      disintegrating tablets--8%; sumatriptan nasal spray 9%; sumatriptan injection,
      9%; nontriptans--19.6%. Most (54%) had no benefit within the first hour of
      treatment. The maximum benefit took more than 1 hour to be reached in 69%, and
      more than 2 hours in 36%. After the maximum benefit had been reached, pain
      worsened in 61%. Although 58% were satisfied with the degree of relief, 37% were
      dissatisfied with the speed of effect, 50% with the recurrence of pain, and 42%
      with the need for a second dose. Most were satisfied with the tolerability (56%).
      Finally, most (79.7%) said they were willing to try another acute medication.
      CONCLUSIONS: An important subset of patients, including a large subgroup of
      patients using triptans, is dissatisfied with their UC. Clinical trials assessing
      patients' preference should be conducted to complement the information from
      clinical trials.

PMID- 17445097
TI  - Patient-centered outcomes for frequent headaches.
AB  - OBJECTIVE: To identify clinical outcomes that headache sufferers consider
      meaningful. BACKGROUND: Several standardized instruments have been developed to
      assess the severity of headaches and the impact of headaches on an individual's
      quality of life. To our knowledge, however, little research has been conducted to
      determine which of these many clinical endpoints are considered by headache
      sufferers themselves to be most important. METHODS: We conducted 4 focus groups
      with patients with frequent headaches who had recently participated in a
      randomized clinical trial. Subjects were informed that the purpose of the focus
      groups was to help healthcare providers learn how to better recognize if their
      patients' headache conditions improved or worsened over time. RESULTS: Five
      salient topics emerged from the discussions: (1) severity of pain associated with
      headaches; (2) definition of meaningful symptom relief; (3) uncertainty regarding
      timing and severity of headaches; (4) devaluation of the impact of headaches on
      sufferers; and (5) assessments of pain. Participants stated unambiguously that
      headache pain is one of the most important aspects of their headache experience.
      Each of the 4 groups agreed that an increase in the number of pain-free days
      would be meaningful. Participants also reported that daily headache diaries are
      not overly burdensome to complete and that the diaries helped them identify
      useful trends over time. CONCLUSIONS: Our findings suggest that severity and
      frequency of headache pain are important clinical outcomes from patients'
      perspective, and that headache diaries are a feasible and useful method of
      assessing meaningful clinical change over time. Although standardized
      questionnaires that assess functional status, disability, or health-related
      quality of life may help quantify patients' response to treatment for frequent
      headaches, participants in this study did not consider such questionnaires
      particularly informative. Further research is needed to validate headache diaries
      among patients with headache in the primary care setting.

PMID- 17445098
TI  - Botulinum toxin type a prophylactic treatment of episodic migraine: a randomized,
      double-blind, placebo-controlled exploratory study.
AB  - OBJECTIVE: This exploratory trial evaluated the safety and efficacy of multiple
      treatments of botulinum toxin type A (BoNTA; BOTOX, Allergan, Inc., Irvine, CA,
      USA) as prophylactic treatment of episodic migraine headaches. DESIGN AND
      METHODS: This was an 11-month randomized, double-blind, placebo-controlled,
      exploratory study. Patients were screened during a 30-day baseline period, and
      eligible patients with 4 or more migraine episodes and < or =15 headache days
      entered a single-blind 30-day placebo run-in period. Patients were classified as
      placebo nonresponders (PNR) if they had at least 4 moderate-to-severe migraine
      episodes and did not experience at least a 50% decrease from baseline in the
      frequency of migraine episodes following their placebo treatment. All other
      subjects were classified as placebo responders (PR). Patients were randomized
      within each stratum (PNR, PR) to 3 treatments with BoNTA (110 to 260 U of BoNTA
      per treatment cycle) or placebo at 90-day intervals using a modified follow-the
      pain treatment paradigm. The primary efficacy outcome measure was the mean change
      from baseline in the frequency of migraine episodes for the 30 days prior to day
      180 in the PNR group. Secondary efficacy measures included the proportion of
      patients with a decrease from baseline of 50% or more migraine episodes per 30
      day period. Patients were allowed to take concomitant acute and prophylactic
      headache medications. Adverse events were reported. RESULTS: A total of 809
      patients were screened and 369 patients (89.2% female; mean age, 45 years; range,
      20 to 65 years) entered the placebo run-in period and were subsequently
      randomized to BoNTA or placebo. The mean total dose of BoNTA was 190.5 units (U)
      (range, 110 U to 260 U). The predetermined primary efficacy endpoint was not met.
      Substantial mean improvements of 2.4 and 2.2 fewer migraine episodes per month at
      day 180 in the PNR stratum treated with BoNTA and placebo, respectively, were
      observed (P > .999). From day 180 through the end of the study (day 270) at least
      50% of all patients in each treatment group had a decrease from baseline of 50%
      or more migraine episodes per 30-day period. However, in the group of patients
      with > or =12 headache days at baseline (and < or =15 headache days), BoNTA
      patients experienced a mean change from baseline of -4.0 headache episodes at day
      180 compared with -1.9 headache episodes in the placebo group (P= .048). The
      majority of treatment-related adverse events were transient and mild to moderate
      in severity. Only 7 patients (1.9%) discontinued the study due to adverse events
      (6 BoNTA, 1 placebo). CONCLUSION: There were no statistically significant between
      group differences in the mean change from baseline in the frequency of migraine
      episodes per 30-day period. There were substantial, sustained improvements during
      the course of the study in all groups. Multiple treatments with BoNTA were shown
      to be safe and well tolerated over an active treatment period lasting 9 months.

PMID- 17445099
TI  - Topiramate in migraine prophylaxis: long-term impact on resource utilization and
      cost.
AB  - OBJECTIVE: To evaluate the medical resource utilization and overall cost of care
      among patients treated with topiramate (TPM) for migraine prevention in a
      commercially insured population. Background.-Preventive migraine therapy with TPM
      significantly reduces the frequency of migraine attacks. Limited data exist on
      the real-world health care consumption associated with TPM therapy for migraine
      prevention. METHODS: Data were obtained from a large geographically diverse
      integrated medical and pharmacy claims database representative of the
      commercially insured population. The date of the first TPM claim between July
      2000 and December 2003 was considered the index date. Patients needed at least 1
      triptan prescription (Rx) claim during the 6-month preindex period, and > or =2
      TPM Rx claims in the 12 months following index TPM Rx to be included in the
      analysis. Headache-related inpatient and outpatient resource use were compared:
      preindex vs postindex period 1 (months 1-6) and preindex vs postindex period 2
      (months 7-12). Subgroup analyses were conducted based on the triptan consumption
      during the 6-month preindex period: Cohort L (low triptan users) with < or =36
      triptan doses, and Cohort H (high triptan users) with >36 triptan doses. RESULTS:
      The sample included 2645 plan members (1778 patients in Cohort L, and 867
      patients in Cohort H). TPM utilization was associated with significantly less
      triptan utilization in the first (34.8 quantity dispensed; 7.5% decrease) and
      second (30.2; 19.6% decrease) follow-up periods compared to the preindex period
      (37.6; both P < .0001). In postindex period 1, there was a 46% decrease in
      emergency department (ED) visits, 39% decrease in diagnostic procedures (eg, CT
      scans and MRIs), and a 33% decrease in hospital admission; physician office
      visits were unchanged. In postindex period 2, there was a 46% decrease in ED
      visits, 72% decrease in diagnostic procedures, 61% decrease in hospital
      admissions, and a 35% decrease in physician office visits. Decreases in resource
      use were observed in both cohorts L and H. Mean +/- SD total headache-related
      cost was $2118 +/- $3406 per patient in the preperiod, versus $2450 +/- $3318 in
      follow-up period 1 and $2009 +/- $3136 in follow-up period 2. CONCLUSION: In this
      sample of patients from a diverse set of health plans receiving TPM, significant
      decreases in resource use were observed within 6 months of TPM initiation, and
      this trend continued in follow-up period 2. Although there was an initial
      increase in total headache-related cost upon introduction of TPM (follow-up
      period 1), the cost in follow-up period 2 was lower than in the preindex period,
      suggesting that benefits of long-term treatment with TPM can be achieved without
      increasing total cost.

PMID- 17445100
TI  - Eletriptan for the acute treatment of migraine in adolescents: results of a
      double-blind, placebo-controlled trial.
AB  - BACKGROUND: Eletriptan is a potent 5-HT(1B/1D) agonist with proven efficacy in
      the acute treatment of migraine in adults. OBJECTIVE: To evaluate the efficacy
      and tolerability of eletriptan 40 mg versus placebo in adolescent patients (aged
      12-17). METHODS: A multicenter, double-blind, parallel-group, placebo-controlled
      trial was conducted comparing 40 mg of oral eletriptan with placebo for the
      treatment of migraine in adolescent patients. The primary efficacy endpoint was 2
      hour headache response, and a number of secondary endpoints were also evaluated.
      An exploratory analysis evaluated which clinical and demographic characteristics
      might be correlated with high placebo response. RESULTS: Of 274 patients who
      treated a migraine attack, 267 were evaluated for efficacy (n = 138 eletriptan; n
      = 129 placebo) at 2 hours post-dose. There was no significant difference in 2
      hour headache response for eletriptan 40 mg versus placebo (57% vs 57%), and no
      significant improvements were observed for any of the outcomes at 1 or 2 hours
      post-dose. By contrast, there was a significant advantage for eletriptan 40 mg in
      reducing headache recurrence within 24 hours post-dose (11% vs 25%, P= .028), and
      post hoc analyses showed statistically significant differences for sustained
      headache response rates (52% vs 39%; P= .04) and sustained pain-free response
      rates (22% vs 10%; P= .013). The strongest clinical predictor of placebo response
      was triptan-naive status (i.e., no previous use of any triptan). Eletriptan 40 mg
      was well tolerated in this population, and the profile of adverse events was
      similar to that observed in Phase III trials in adult patients. CONCLUSIONS: The
      high placebo response rates reported here for 1- and 2-hour outcomes are in
      accordance with other studies of triptans in adolescent patients. The evaluation
      of treatment effect in adolescent migraine might benefit from use of more
      stringent outcome measures, such as headache recurrence, sustained headache
      response, and sustained pain-free response at 24 hours post-dose.

PMID- 17445101
TI  - Effect of pain intensity and time to administration on responsiveness to
      almotriptan: results from AXERT 12.5 mg Time Versus Intensity Migraine Study
      (AIMS).
AB  - OBJECTIVE: To determine whether time-based early treatment, independent of pain
      intensity, is superior to a pain intensity-based treatment, where patients are
      asked to treat at least moderate intensity headaches, resulting in a reduction of
      overall migraine headache duration. BACKGROUND: Retrospective and prospective
      trials have reported improved outcomes when triptans were used early or to treat
      mild migraine headache pain. However, tolerability as well as efficacy may be 2
      of several key issues that have prevented this new treatment paradigm from
      becoming universally accepted. METHODS: In this multicenter, open-label, cluster
      randomized study, patients with IHS-defined migraine were instructed to treat 2
      sequential migraine headaches with almotriptan 12.5 mg using either Early
      Treatment (ET, ie, treat at earliest onset of headache pain, within 1 hour) or
      Standard Treatment (ST, ie, treat when headache pain intensity is moderate or
      severe). The novel trial design uses total migraine headache pain duration as the
      primary endpoint. RESULTS: Results are presented for the first headache and
      include an ITT population of 757 ET and 693 ST patients. Median headache duration
      (time from onset of headache pain until no pain) was significantly shorter in ET
      patients compared to ST patients (3.18 vs 5.53 hours, P < .001). An analysis of
      the ET subgroup treating headache pain within 1 hour of onset revealed pain
      intensity, ie, treating mild or moderate versus severe pain, was significantly
      correlated with treatment outcomes defined by total headache duration, 2-hour
      pain free, sustained pain free, and use of rescue medication. Multivariate
      analyses comparing ST subgroups that treated within 1 hour versus greater than 1
      hour after headache onset, demonstrate that both pain intensity, ie, treating
      moderate versus severe headache pain, and treating early versus late, were
      significantly correlated with total headache duration, 2-hour pain free,
      sustained pain free, and use of rescue medication. The overall incidence of
      adverse events was low; nausea and dizziness were the only adverse events with an
      incidence > or =1% in either treatment group (nausea: 2.5% and 1.7% and dizziness
      1.1% and 0.7%, in the ET and ST groups, respectively). CONCLUSION: Total headache
      duration was significantly shorter in the early treatment group compared to the
      standard treatment group. Considering time to treatment within a relatively early
      range of 1 hour or less, efficacy results when treating mild versus moderate pain
      were similar and both were associated with better outcomes than treatment of
      severe pain. When considering the prognostic variables of time to treatment and
      headache pain intensity (limited to moderate vs severe), both were independent
      predictors, with time to treatment a better predictor of headache duration and
      rescue medication use, and pain intensity a better predictor of 2-hour pain free
      and sustained pain free.

PMID- 17445102
TI  - Cutaneous allodynia in transformed migraine patients.
AB  - BACKGROUND: There is growing evidence that central sensitization plays a role in
      migraine pathogenesis, and that cutaneous allodynia is its clinical correlate. In
      headache research, allodynia has largely been studied in episodic migraine. The
      purpose of this investigation was to determine whether cutaneous allodynia occurs
      in transformed migraine, using individuals without headaches as controls.
      METHODS: Fifteen patients with a diagnosis of transformed migraine and 15 control
      subjects with no history of headaches were included. All subjects were females
      between 18 and 50. Similar to the methods of Burstein et al, Von Frey hairs (VFH)
      were sequentially applied to territories supplied by divisions of the trigeminal
      nerve, cervical paraspinal muscles, trapezius muscles, ventral forearm, and lower
      leg to determine a pain threshold. As a milder stimulus, a cotton swab was
      stroked in the same locations. Each trial was repeated 3 times on 2 occasions.
      Group comparisons were made using the Student's t-test. RESULTS: Mean pain
      thresholds were lower among migraine patients than control subjects across all
      test areas. The thresholds were statistically significantly lower in migraine
      patients than in control subjects for the 1st division of the trigeminal nerve
      (34.0 g versus 115.8 g, P= .035) and for the 2nd division (23.5 g versus 97.6 g,
      P= .039). Six patients found a cotton swab-stroke painful, compared to zero
      control subjects. Using a quantitative definition of allodynia, 75% of patients
      had allodynia to mechanical stimuli. CONCLUSIONS: This study is the first to
      demonstrate allodynia in transformed migraine patients using a headache-free
      control population and supports the hypothesis that central sensitization plays a
      role in the evolution of transformed migraine.

PMID- 17445103
TI  - Patients' preference for migraine preventive therapy.
AB  - OBJECTIVE: Preventive treatment is an important part of migraine therapy. When
      prescribing medication, physicians should understand patients' treatment
      preferences and select drugs that most closely meet their patients' needs.
      Understanding the factors that influence patients' preference increases
      physicians' ability to select appropriate migraine therapy. However, unlike acute
      migraine treatment, patients' preferences for migraine preventive treatment have
      never been studied. METHODS: We enrolled 250 patients who attended the Jefferson
      Headache Center and Sao Paulo Headache Center and had a primary headache
      diagnosis. Patients' age, gender, body mass index (BMI), headache diagnosis,
      headache frequency, duration, and intensity, headache disability (by MIDAS), and
      current preventive treatments were ascertained. Patients were asked to rate 7
      aspects of headache prevention (efficacy, speed of onset, out-of-pocket expenses,
      adverse events, formulation of therapy, type of treatment, and frequency of
      dosing) in order of importance (1-7). Each patient also evaluated 12 different
      clinical scenarios, each one containing a simulation of 2 hypothetical headache
      preventive treatments, wherein patients could choose Product A, Product B, or
      neither. Patients were informed of each product's efficacy data (50%, 75%, or
      100% headache elimination), adverse event profile (weight gain, concentration
      difficulty, and/or fatigue), and dosing frequency (once every 3 months, once per
      day, or twice per day). RESULTS: Most patients were Caucasian. Mean BMI was 26.55
      +/- 5.34, range (17-45). Mean history of headache was 20.93 years. Fifty patients
      (40%) had 45 or more headache days in the past 3 months. Mean headache intensity
      score (0-10 scale) was 5.7 +/- 1.8. Patients were on various preventive
      treatments, including beta-blockers (48 [41%]), calcium-channel blockers (19
      [16%]), antidepressants (52 [44%]), antiepileptics (46 [39%]), neurotoxins (16
      [14%]), vitamins/herbal therapies (28 [24%]), and nonmedicinal therapy (38
      [32%]). Of the 7 aspects of migraine prevention that patients were asked to rate,
      72% rated effectiveness the most important aspect. Twelve percent rated speed of
      onset most important, 6% rated absence of adverse events most important, 3% rated
      formulation of therapy most important, 3% rated out-of-pocket expenses most
      important, and 2% rated type of treatment (prescription/vitamin) most important.
      None rated frequency of dosing as the most important factor. In the area of
      preventive treatment scenarios, patients were more likely to choose treatments
      with higher efficacy rates, fewer adverse events and less frequent dosing
      schedule. Patients indicated that they preferred the treatment options with
      higher efficacy rates even if side effects were present and a more frequent
      dosing schedule was necessary. CONCLUSION: Patients' preference regarding
      migraine prevention is very important in headache management. Patients rated
      efficacy the most important aspect in preventive therapy and preferred treatment
      options with higher efficacy rates. Future studies are needed for a better
      understanding of patients' preference for migraine prevention.

PMID- 17445104
TI  - Validation of a german language questionnaire for screening for migraine, tension
      type headache, and trigeminal autonomic cephalgias.
AB  - BACKGROUND: To develop a German language questionnaire for screening for
      migraine, tension-type headache, and trigeminal autonomic cephalgias. OBJECTIVE:
      Aim of the study was to develop a German language self-administered headache
      questionnaire for screening for migraine (MIG), tension-type headache (TTH), and
      trigeminal-autonomic cephalgias (TAC). METHODS: Questionnaire-based diagnoses
      were blindly compared with those of headache experts. RESULTS: Overall 278
      headache patients (MIG = 97, TTH = 60, TAC = 98, MIG plus TTH = 23) as well as 42
      patients with low back pain without headache and 47 healthy subjects were
      studied. The Cohen's kappa for 7 headache syndromes including all combination
      diagnoses was 0.64 (95% CI 0.58-0.70). Sensitivity and specificity for migraine
      were 0.73 and 0.96, for TTH 0.85 and 0.98, for TAC 0.63 and 0.99, and for MIG
      plus TTH 0.62 and 0.97, respectively. Ignoring all combination diagnoses, the
      kappa-coefficient for the monodiagnoses MIG, TTH, and TAC (193 out of 278
      patients) was 0.93 (CI 0.83-1.0). The retest-reliability (4 weeks later) was
      0.95. CONCLUSION: We present the first questionnaire in German language including
      3 most common primary headaches for use in epidemiological research.

PMID- 17445105
TI  - Sensitization of the trigeminal sensory system during different stages of the rat
      estrous cycle: implications for menstrual migraine.
AB  - OBJECTIVES: To determine if the sensitization of the trigeminal system changes
      after dural activation of the trigeminal nerve during different stages of the rat
      estrous cycle. BACKGROUND: The specific mechanisms through which ovarian hormones
      trigger menstrual migraine are currently unknown. Past animal studies have
      suggested that the response properties of the trigeminal nucleus caudalis (TNC)
      may change during the different phases of the rat estrous cycle, but none have
      been performed in an experimental paradigm for migraine headache. METHODS: Sixty
      one cycling female Sprague-Dawley rats were used for these experiments. The stage
      of the estrous cycle of each animal was identified by examination of the cellular
      morphology of vaginal lavage. The animals were anesthetized and a 7 mm portion of
      the skull was removed that was centered over the sagittal sinus. A tungsten
      electrode was used to record from neurons in the TNC or CI-CIII regions. Only
      neurons that had both dural and cutaneous receptive fields were used for these
      experiments. Facial receptive field sizes (RFS) were mapped and neurophysiologic
      response properties of the TNC/CI-CIII neurons to cutaneous and dural stimuli was
      ascertained before and after application of capsaicin to the dura. One-way and
      repeated measure analysis of variance were used to compare changes in RFS and
      response properties of TNC/CI-CIII neurons from animals during different stages
      of the rat estrous cycle. RESULTS: When data were analyzed individually for each
      stage, there was greater enlargement of cutaneous receptive fields and enhanced
      sensitivity of the trigeminal system to cutaneous stimuli during proestrus as
      compared to metestrus and diestrus after dural activation with capsaicin (P
      values <.05). When data were pooled from stages with similar hormonal milieus,
      the percent change in the response magnitude of TNC neurons to electrical
      stimulation of the dura was greater and receptive field enlargement was larger
      from the proestrous/estrous group compared to those from the metestrous/diestrous
      group after administration of capsaicin (P values <.05). CONCLUSIONS: There is
      enhanced sensitization of the trigeminal system during the later halves of
      proestrus and estrus, which represent stages of the rat estrous cycle during and
      immediately following an abrupt decline in ovarian hormones. If similar changes
      occur during the human menstrual cycle these results could have important
      implications for menstrual migraine.

PMID- 17445106
TI  - Effects of female sex hormones on responses to CGRP, acetylcholine, and 5-HT in
      rat isolated arteries.
AB  - BACKGROUND: Female sex hormones are implicated in the modulation of reactivity of
      a wide range of blood vessels under physiological as well as pathological
      conditions. Migraine, a neurovascular syndrome, is 3 times more prevalent in
      women during their reproductive period than in men. OBJECTIVE: This study sets
      out to investigate the effects of the female sex steroids, 17beta-estradiol and
      progesterone (separately and in combination) on vasoactive responses to
      calcitonin gene-related peptide (CGRP), acetylcholine, and 5-hydroxytryptamine (5
      HT) in rat isolated mesenteric, caudal, and basilar arteries. METHODS: Female
      Sprague-Dawley rats were ovariectomized (Day 0) and 7 days later subcutaneously
      implanted with pellets releasing over a 21-day period 17beta-estradiol (0.25 mg),
      progesterone (50 mg), their combination, or placebo. On days 25-28, the animals
      were killed, arteries isolated and mounted in Mulvany myographs, and cumulative
      concentration response curves to CGRP, acetylcholine, and 5-HT were constructed.
      RESULTS: The relaxant responses to CGRP were significantly potentiated in
      mesenteric and caudal arteries from rats treated with 17beta-estradiol as
      compared to the placebo-treated rats. Acetylcholine-induced relaxations were
      potentiated in the caudal artery from rats treated with the combination of 17beta
      estradiol and progesterone, as compared to that from placebo-treated rats. The 5
      HT-induced contractions in the 3 arteries were not significantly different in
      efficacy or potency. CONCLUSION: Our results show that 17beta-estradiol
      potentiates CGRP-induced relaxations in the mesenteric and caudal arteries, while
      the combination treatment enhances acetylcholine-induced relaxations in the
      caudal artery. Although these in vitro experiments have been carried out in rats
      and a direct extrapolation to migraine in humans is not possible, our results may
      provide a new avenue to study the effects of sex steroids on vascular reactivity.

PMID- 17445107
TI  - Association between stress at work and primary headache among nursing staff in
      Taiwan.
AB  - BACKGROUND: Stress, one of the most commonly identified triggers for primary
      headache in the workplace, usually leads to inefficient work during attacks.
      Stress-related primary headaches in the nursing staff of hospitals have received
      little attention. OBJECTIVE: To realize the association between stress and
      headache, and the means of coping with this kind of headache. METHODS: A cross
      sectional, hospital-based study using a semi-structured questionnaire was
      administered to 900 nursing staffers in a tertiary medical center in southern
      Taiwan. Thirty-two items, including basic information, headache- and stress
      related questions, work satisfaction, and coping strategies were measured.
      Headache sufferers with either migraine or episodic tension headache (attacks <15
      days per month) based on International Headache Society (IHS) criteria were
      enrolled for analysis. The Student's t-test, one-way analysis of variance
      (ANOVA), and chi-square test were used for statistical analysis. RESULTS: Three
      hundred eighty-six out of 779 responders (49.6%) had experienced primary
      headaches in the previous year, and 374 (48.1%) had had episodic-type headaches
      (<15 days/month). A careful neurological interview of the latter group revealed
      that 222 (28.5%) had migraine, 104 (13.4%) had tension headache, 37 (4.8%) had
      mixed migraine and tension headache, and 11 (1.4%) had other causes of headache.
      There were no demographic differences between the sufferers and nonsufferers,
      although a statistically significant difference was noted in self-reported
      sources of stress (individual P values ranged from .021 to < .001). Headache
      sufferers had more stress at work than non-headache sufferers (P < .001). The
      youngest and least experienced of the nursing staff, the unmarried, and those
      with a lower level of education had a higher level of stress. The methods used to
      deal with headaches were sleep, taking medicine, taking a rest, visiting the
      doctor, and seeking psychological help. Nurses commonly used acetaminophen
      (panadol--500 mg) to relieve their pain. CONCLUSION: These results indicate that
      stress at work is associated with primary headaches among nursing staff, and that
      nurses rarely seek help in the beginning. Therefore, nursing staff education
      aimed at ameliorating the stress and coping with the headaches, thus allowing the
      nurses to provide better patient care, may be warranted.

PMID- 17445108
TI  - Pharmacological approaches to managing migraine and associated comorbidities-
      clinical considerations for monotherapy versus polytherapy.
AB  - Comorbidity is defined as an illness that occurs more frequently in association
      with a specific disorder than would be found as a coincidental association in the
      general population. Conditions that are frequently comorbid with migraine include
      depression, anxiety, stroke, epilepsy, sleep disorders, and other pain disorders.
      In addition, many common illnesses occur concomitantly (at the same time) with
      migraine and influence the treatment choice. Migraine management, and especially
      migraine prevention, can be challenging when patients have comorbid or
      concomitant illnesses. The objectives of this initiative are to review the
      literature on managing patients who have migraine and common comorbidities,
      present additional clinical approaches for care of these difficult patients, and
      evaluate the areas in which research is needed to establish evidence-based
      guidelines for the management of migraine with associated comorbid conditions.

PMID- 17445109
TI  - Steroids and aseptic osteonecrosis (AON) in migraine patients.
AB  - Osteonecrosis is a bony infarction caused by disruption of blood supply to the
      bone. Aseptic osteonecrosis should be rare with intermittent use of steroids in
      disabling and refractory migraine cases. We present 3 cases of patients who had
      severe migraine and developed aseptic osteonecrosis with short-term, intermittent
      pulse doses of corticosteroids. Migraine has been mentioned as a possible risk
      factor for aseptic osteonecrosis, and we speculate that severe migraine may be a
      risk factor for developing aseptic osteonecrosis. Furthermore, migraineurs who
      develop aseptic osteonecrosis may or may not have associated white matter changes
      in the brain. We noted a triad of severe migraine, osteonecrosis, and migraine
      related white matter lesions in only 1 case. In severe cases of migraine,
      steroids should be used cautiously.

PMID- 17445110
TI  - Vertebral artery dissection in a migraine patient with recurrent drop attacks.

PMID- 17445111
TI  - Motion sickness and migraine.

PMID- 17445112
TI  - Spontaneous low-pressure headache complicating bag-piping.
AB  - We describe an interesting case of a 40-year-old lady who developed a spontaneous
      low-pressure headache whilst playing the bag-pipes. Playing wind instruments
      requires the generation of significant intra-thoracic pressure, which may have
      contributed to this musician's condition.

PMID- 17445113
TI  - Intrathecal gadolinium-enhanced MR-cisternography in spontaneous intracranial
      hypotension associated with Behcet's syndrome.
AB  - We report a 32-year-old woman diagnosed with spontaneous intracranial hypotension
      (SIH) and Behcet's Syndrome. Suspicion of SIH was based on cervical MRI findings,
      and magnetic resonance (MR)-cisternography revealed dural leaks bilaterally at
      lumbar region. MR-cisternography is a recently performed technique and gaining
      importance in demonstration of CSF fistula.

PMID- 17445114
TI  - Topiramate for migraine prophylaxis among Chinese population.
AB  - We evaluated the efficacy and safety of topiramate for migraine prophylaxis among
      Chinese patients in a multicenter prospective observational study. We found that
      topiramate at low doses was effective in preventing migraine headache in Chinese
      patients and was generally well tolerated. There was no difference in baseline
      headache frequency or intensity between responders and nonresponders.

PMID- 17445115
TI  - A case of hypertrophic pachymeningitis with prolonged headache, attributable to
      Epstein-Barr virus.
AB  - Hypertrophic pachymeningitis is a condition characterized by significant chronic
      inflammatory thickening of the cranial dura mater, frequently presenting with
      symptoms such as headache and cranial neuropathy. In this report, we describe a
      very rare case of hypertrophic pachymeningitis, considered to be attributable to
      Epstein-Barr virus (EBV), which was diagnosed in a patient who visited our
      hospital with a complaint of ongoing severe headaches. The diagnosis was based on
      positive specific serum EBV antibody titers, with VCA-IgM levels of less than
      1:10, VCA-IgG levels of 1:160, and EBNA levels of 1:40, as well as on the results
      of magnetic resonance imaging of the head with contrast media.

PMID- 17445117
TI  - Acetaminophen, aspirin, and caffeine versus sumatriptan succinate in the early
      treatment of migraine: results from the ASSET trial--a comment.

PMID- 17445119
TI  - Teaching case: Cervicogenic headache.

PMID- 17445120
TI  - Patient information regarding subcutaneous self-administration of sumatriptan
      (imitrex).

PMID- 17445121
TI  - Mechanical prophylaxis for travellers' thrombosis: a comparison of three
      interventions that promote venous outflow.

PMID- 17445122
TI  - Inhibitors, what is the risk of treatment intensity?

PMID- 17445123
TI  - Abstracts of the 40th Annual Scientific Meeting of the Australasian College of
      Dermatology. May 13-16, 2007. Adelaide, South Australia, Australia.

PMID- 17445124
TI  - Editorial: new international guidelines for wastewater use in agriculture.

PMID- 17445125
TI  - Rapid achievement of the child survival millennium development goal: evidence
      from the Navrongo experiment in Northern Ghana.
AB  - OBJECTIVE: To determine the impact of deploying nurses and volunteers to village
      locations on demographic and health outcomes. METHOD: We implemented an
      experimental design that emphasizes the value of aligning community health
      services with traditional social institutions that organize village life. Data
      for this analysis come from the Navrongo demographic surveillance system, a
      longitudinal database that tracks fertility, mortality, and migration events over
      time. The experiment uses conventional demographic methods for estimating
      mortality rates from longitudinal demographic surveillance registers. RESULTS:
      Posting nurses to community locations reduced childhood mortality rates by over
      half in 3 years and accelerated attainment of the childhood-survival millennium
      development goal (MDG) in the study areas relative to trends observed in
      comparison areas. CONCLUSION: Results from the Navrongo experiment demonstrate
      that community health and family planning programmes can have an impact on
      childhood mortality. Posting nurses to communities can dramatically accelerate
      the pace of progress in achieving the childhood-survival MDGs. Community
      volunteer approaches, however, have no additional impact, a finding that
      challenges the child survival value of international investment in volunteer
      based health programmes. The total cost of the intensive arm of the project is
      less than $10 per capita per year. Navrongo research thus demonstrates affordable
      means of attaining the child survival MDG agenda with existing technologies.

PMID- 17445126
TI  - Poorer health and nutritional outcomes in orphans and vulnerable young children
      not explained by greater exposure to extreme poverty in Zimbabwe.
AB  - OBJECTIVE: To describe patterns of association between different groups of young
      orphans and vulnerable children (OVC) and their nutritional and health outcomes;
      and to develop a theoretical framework to analyse the determinants of child
      malnutrition and ill-health, and identify the different mechanisms which
      contribute to these outcomes in such children. METHODS: We developed and tested a
      theoretical framework to explain why orphans and vulnerable children experience
      more ill-health and malnutrition based on statistical analysis of data on 31 672
      children aged 0-17 years (6753 aged under 5 years) selected from the Zimbabwe OVC
      Baseline Survey 2004. RESULTS: 28% of children aged 0-4 years at last birthday
      were either orphans or vulnerable children. They were more likely than non
      vulnerable children to have suffered recently from diarrhoeal illness (age- and
      sex-adjusted odds ratio, AOR, 1.27; 95% CI 1.09-1.48) and acute respiratory
      infection (1.27; 1.01-1.59) and to be stunted (1.24; 1.09-1.41) and underweight
      (1.18; 1.02-1.36). After further adjustment for exposure to extreme poverty, OVC
      remained at greater risk of diarrhoeal disease (AOR 1.25; 1.07-1.46) and chronic
      malnutrition (1.21; 1.07-1.38). In 0-17-year-olds, OVC with acute respiratory
      infection were more likely not to have received any treatment even after
      adjusting for poverty (AOR 1.29; 95% CI 1.16-1.43). CONCLUSION: Differences in
      exposure to extreme poverty among young children by OVC status were relatively
      small and did not explain the greater malnutrition and ill-health seen in OVC.

PMID- 17445127
TI  - Early growth of infants of HIV-infected and uninfected Zambian women.
AB  - OBJECTIVE: Parental HIV infection may affect even those exposed children who
      remain uninfected. We investigated early growth, an indicator of overall health,
      of infants born to Zambian mothers recruited for a study of breastfeeding and
      postpartum health. METHODS: HIV-infected and uninfected women in Lusaka were
      followed regularly from late pregnancy to 16 weeks postpartum. Infant weight and
      length were measured at birth, 6 and 16 weeks. Infant HIV status could not be
      specifically determined in this cohort so comparisons were between all infants of
      HIV-uninfected mothers (n = 184) and those infants of HIV-infected mothers who
      were known to be alive and showed no clinical evidence of HIV infection at age 2
      4 years (n = 85). RESULTS: Most infants were exclusively or predominantly
      breastfed until 16 weeks. At all time points infants of HIV-infected mothers
      tended to have lower weight and length standard deviation (Z) scores (significant
      for weight at 6 weeks; P = 0.04), even after adjustment for their lower
      gestational age at birth, compared with infants of uninfected mothers. In
      multivariate analyses the major factors affecting weight or length at 6 or 16
      weeks of age were birth weight or length, and maternal subclinical mastitis,
      primiparity and weight during pregnancy. CONCLUSIONS: Early growth of infants of
      HIV-infected mothers is less than that of uninfected mothers, in part associated
      with subclinical mastitis, and this effect cannot be overcome with intensive
      support of mothers to follow international recommendations regarding exclusive
      breastfeeding.

PMID- 17445128
TI  - Delayed cord clamping and haemoglobin levels in infancy: a randomised controlled
      trial in term babies.
AB  - OBJECTIVES: This study was carried out to assess whether delaying umbilical cord
      clamping is effective in improving the haematological status of term infants
      living in a malaria-endemic area, and whether this is associated with
      complications in infants and mothers. METHODS: We randomly assigned women
      delivering term babies in Mpongwe Mission Hospital, Zambia, to delayed cord
      clamping (DCC, n = 46) or immediate cord clamping (controls, n = 45) and followed
      their infants on a bi-monthly basis until the age of 6 months. We compared the
      haemoglobin (Hb) change from cord values and the proportion of anaemic infants.
      Secondary outcomes related to infant and maternal safety. RESULTS: Throughout the
      observation period infant Hb levels in both groups declined, but more rapidly in
      controls than in the DCC group [difference in Hb change from baseline at 4 months
      1.1 g/dl, 95% confidence interval (CI) 0.2; 2.1]. By 6 months, this difference
      had disappeared (0.0 g/dl, 95% CI -0.9; 0.8). The odds ratio for iron deficiency
      anaemia in the DCC group at 4 months was 0.3 (95% CI 0.1; 1.0), but no
      differences were found between the groups at 6 months. No adverse events were
      seen in infants and mothers. CONCLUSION: Our findings indicate that DCC could
      help improve the haematological status of term infants living in a malaria
      endemic region at 4 months of age. However, the beneficial haematological effect
      disappeared by 6 months. This simple, free and safe delivery procedure might
      offer a strategy to reduce early infant anaemia risk, when other interventions
      are not yet feasible.

PMID- 17445130
TI  - Exposure to mixed asymptomatic infections with Trypanosoma cruzi, Leishmania
      braziliensis and Leishmania chagasi in the human population of the greater
      Amazon.
AB  - Lack of conservation of the Amazon tropical rainforest has imposed severe threats
      to its human population living in newly settled villages, resulting in outbreaks
      of some infectious diseases. We conducted a seroepidemiological survey of 1100
      inhabitants of 15 villages of Paco do Lumiar County, Brazil. Thirty-five (3%)
      individuals had been exposed to Trypanosoma cruzi (Tc), 41 (4%) to Leishmania
      braziliensis (Lb) and 50 (4.5%) to Leishmania chagasi (Lc) infections. Also, 35
      cases had antibodies that were cross-reactive against the heterologous
      kinetoplastid antigens. Amongst these, the Western blot assays revealed that 11
      (1%) had Tc and Lb, that seven (0.6%) had Lc and Tc, and that 17 (1.6%) had Lb
      and Lc infections. All of these cases of exposures to mixed infections with
      Leishmania sp, and eight of 11 cases of Tc and Lb were confirmed by specific PCR
      assays and Southern hybridizations. Two cases had triple infections. We consider
      these asymptomatic cases showing phenotype and genotype markers consistent with
      mixed infections by two or more kinetoplastid flagellates a high risk factor for
      association with Psychodidae and Triatominae vectors blood feeding and
      transmitting these protozoa infections. This is the first publication showing
      human exposure to mixed asymptomatic kinetoplastid infections in the Amazon.

PMID- 17445129
TI  - Malaria deaths as sentinel events to monitor healthcare delivery and antimalarial
      drug safety.
AB  - OBJECTIVES: To identify case management, health system and antimalarial drug
      factors contributing to malaria deaths. METHOD: We investigated malaria-related
      deaths in South Africa's three malaria endemic provinces from January 2002 to
      July 2004. Data from healthcare facility records and a semi-structured interview
      with patients' contacts were reviewed by an expert panel, which sought to reach
      consensus on factors contributing to the death. This included possible health
      system failures, adverse reactions to antimalarials, inappropriate medicine use
      and failing to respond to treatment. RESULTS: Approximately 177 of 197 cases met
      inclusion criteria for the study. Delay in seeking formal health care was
      significantly longer for patients who sought traditional health care [median 4;
      inter-quartile range (IQR) 3-7 days] than for patients who did not (median 3; IQR
      1-5 days; P = 0.033). Patients with confirmed or suspected HIV/AIDS were
      significantly more likely to use traditional approaches (25%) than those with
      other comorbidities (0%; P = 0.002). Malaria was neither suspected nor tested for
      at a primary care facility in 23% of cases with adequate records. Initial
      hospital assessment was considered inadequate in 74% of cases admitted to
      hospital and in-patient monitoring and management was adequate in only 27%. There
      were 32 suspected adverse reactions to antimalarial therapy. CONCLUSION: A
      confidential enquiry into malaria-related deaths is a useful tool for identifying
      preventable factors, health system failures and adverse events affecting malaria
      case management.

PMID- 17445131
TI  - A correlative study of ultrasound with serology in an area in China co-endemic
      for human alveolar and cystic echinococcosis.
AB  - We correlated ultrasound (US) imaging classifications for human alveolar
      echinococcosis (AE) and cystic echinococcosis (CE) with serology (ELISA and
      immunoblotting (IB) incorporating native and recombinant/purified echinococcal
      antigens) in community surveys (2001-2003) and follow-up (2002 and 2003) of US
      confirmed cases in Ningxia, China. One hundred and seventy-one cases (96 with AE,
      75 with CE) were identified; of these, US classification and serological data
      were obtained for 142 and 112 cases, respectively. Seropositive-rates increased
      in CE patients with highly viable unilocular cyst lesions (Types CL, CE 1 or CE
      2) to degenerating primary lesions (CE 3), but then decreased in subjects with
      inactive (CE 4) or dead (CE 5) cysts. In contrast, there was a constant increase
      in seropositivity from the early (P1, P2) to the advanced stages (P3, P4) with AE
      cases. For US-confirmed cases, follow-up by US combined with serology is
      invaluable for studying the clinical progression of echinococcosis and for
      detecting recurrent cysts or reinfection post-treatment.

PMID- 17445132
TI  - Trend of case detection and leprosy elimination in Brazil.
AB  - Only six countries did not meet the leprosy elimination target during 2005,
      amongst them Brazil. In 2006, the Brazilian Ministry of Health announced a
      reduction of the detection rate of 24% or 10 900 cases from 2004 to 2005. A
      negative binomial parabolic regression model was adjusted to the detection rate
      historical series from 1980 to 2004, in order to predict the 2005 detection rate
      and its 95% confidence interval. This analysis showed that the number of new
      leprosy cases for 2005 could not be predicted from the previous behaviour of the
      data what calls for an epidemiological or operational explanation hypothesis. The
      hypothesis that this drop in detected case number is due to operational change,
      as a reduction in diagnosis or a modification in the reporting routine, is more
      likely. Recent change in prevalence case definition turned the prevalence ratio a
      function of only one variable, the detection rate, as the duration of the
      diagnosed disease became fixed. In the early nineties, based on epidemiological
      data evaluation, the BMoH recognized the impossibility of reaching the
      elimination goal, but it committed to seek leprosy control. This position changed
      after some years. Leprosy Elimination is a strategy supported by the national and
      international public opinion. As a one for all recipe, it may cause unwanted
      effects for it is not flexible enough to deal with different epidemiological
      behaviours and public health traditions.

PMID- 17445133
TI  - Longitudinal analysis of community health workers' adherence to treatment
      guidelines, Siaya, Kenya, 1997-2002.
AB  - OBJECTIVES: To investigate community health workers' (CHW) adherence over time to
      guidelines for treating ill children and to assess the effect of refresher
      training on adherence. METHODS: Analysis of 7151 ill-child consultations
      performed by 114 CHWs in their communities from March 1997-May 2002. Adherence
      was assessed with a score (percentage of recommended treatments that were
      prescribed), calculated for each consultation. Recommended treatments were those
      that were indicated based on CHW assessments. We used piecewise regression models
      to evaluate adherence before and after training. RESULTS: The average adherence
      score was 79.4%. Multivariable analyses indicate that immediately after the first
      refresher training, the mean adherence level improved for patients with a severe
      illness, but worsened for patients without severe illness. Adherence scores
      declined rapidly during the 6 months after the second refresher training.
      CONCLUSIONS: The first refresher was partially effective, the second refresher
      had an effect contrary to that intended, and patient characteristics had a strong
      influence on adherence patterns. Longitudinal studies are useful for monitoring
      the dynamics of CHW performance and evaluating effects of quality improvement
      interventions.

PMID- 17445134
TI  - Community participation in Aedes aegypti control: a sociological perspective on
      five years of research in the health area ''26 de Julio'', Havana, Cuba.
AB  - OBJECTIVE: Effective dengue prevention and Aedes aegypti control is a priority
      for the Cuban health authorities. To enhance effectiveness, strategies oriented
      towards a more active involvement of communities in control activities are being
      tested. This paper presents a sociological perspective on a pilot project
      conducted in the health area ''26 de Julio'' (La Havana) in 1999-2004. METHODS:
      Instrumental case study based on an exhaustive content analysis of project
      documents and on observations of a sociologist. RESULTS: The context and the
      pilot project are systematically described and an analysis of the evolution of
      the underlying concept of community participation is provided. The pilot
      experience was a dynamic process influenced by self-reflection of the research
      team, feedback from research partners and changes in the epidemiological context
      (provoked by two dengue outbreaks during the study period). Community
      participation evolved from being just one component in Aedes aegypti control
      directed by the health staff into a learning and empowering process for the
      people. This change in the concept of participation was reflected in different
      aspects of the pilot project such as the learning and evaluation processes.
      CONCLUSION: Empirical evidence from 5 years of research in the particular context
      of Cuba showed that moves towards community-based Aedes aegypti control are
      feasible. However, in order to be successful, community-based dengue prevention
      should be a social learning process, implying a transfer of power and
      responsibilities to local people. Actions undertaken must be oriented towards
      creating local capabilities, strengthening existing structures and organizations
      and promoting group work for learning participation from participation itself.

PMID- 17445135
TI  - Treatment-seeking behaviour, cost burdens and coping strategies among rural and
      urban households in Coastal Kenya: an equity analysis.
AB  - Ill-health can inflict costs on households directly through spending on treatment
      and indirectly through impacting on labour productivity. The financial burden can
      be high and, for poor households, contributes significantly to declining welfare.
      We investigated socio-economic inequities in self-reported illnesses, treatment
      seeking behaviour, cost burdens and coping strategies in a rural and urban
      setting along the Kenyan coast. We conducted a survey of 294 rural and 576 urban
      households, 9 FGDs and 9 in-depth interviews in each setting. Key findings were
      significantly higher levels of reported chronic and acute conditions in the rural
      setting, differences in treatment-seeking patterns by socio-economic status (SES)
      and by setting, and regressive cost burdens in both areas. These data suggest the
      need for greater governmental and non-governmental efforts towards protecting the
      poor from catastrophic illness cost burdens. Promising health sector options are
      elimination of user fees, at least in targeted hardship areas, developing more
      flexible charging systems, and improving quality of care in all facilities. The
      data also strongly support the need for a multi-sectoral approach to protecting
      households. Potential interventions beyond the health sector include supporting
      the social networks that are key to household livelihood strategies and promoting
      micro-finance schemes that enable small amounts of credit to be accessed with
      minimal interest rates.

PMID- 17445136
TI  - Risk factors for treatment denial and loss to follow-up in an antiretroviral
      treatment cohort in Kenya.
AB  - OBJECTIVES: To evaluate risk factors for treatment denial and loss to follow-up
      in an antiretroviral treatment (ART) cohort in a rural African setting in western
      Kenya. METHOD: Sociodemographic and clinical data of patients enrolled in an ART
      cohort were collected within 18 months of an observational longitudinal study and
      analysed by logistic and Cox regression models. RESULTS: Of 159 patients with
      treatment indication 35 (22%) never started ART. Pregnancy [adjusted odds ratio
      (AOR) 3.60, 95% confidence interval (CI) 1.10-11.8; P = 0.035] and lower level of
      education (AOR 3.80, 95% CI 1.14-12.7; P = 0.03) were independently associated
      with treatment denial. The incidence of total loss of patients under therapy was
      43.2 per 100 person years (pys) (mortality rate 19.2 per 100 pys plus drop out
      rate 24 per 100 pys). Older age [adjusted hazard ratio (AHR) 1.06, 95% CI 1.01
      1.12; P = 0.04], AIDS before starting treatment (AHR 5.83, 95% CI 1.15-29.5; P =
      0.03) and incomplete adherence to treatment (AHR 1.05, 95% CI 1.03-1.07; P <
      0.001) were independent risk factors for death. Incomplete adherence also
      independently predicted drop out because of other reasons (AHR 1.06, 95% CI 1.04
      1.09; P < 0.001). CONCLUSION: Pregnancy and lower level of education, higher age,
      advanced AIDS stage and impaired compliance to ART were identified as risk
      factors for treatment denial and death, respectively. Adequate counselling
      strategies for patients with these characteristics could help to improve
      adherence and outcome of treatment programmes in resource-limited settings.

PMID- 17445137
TI  - MDR and XDR - the price of delaying engagement with all care providers for
      control of TB and TB/HIV.

PMID- 17445138
TI  - How to measure the prevalence of tuberculosis in a population.
AB  - The World Health Assembly has defined targets for measuring performance of
      tuberculosis (TB) control programmes, which have been included in the framework
      of the Millennium Development Goals. To be able to measure progress towards these
      targets TB control programmes need epidemiological information. At the moment,
      surveillance data of countries with a high burden of TB are insufficient to
      assess performance of the TB control programme as a result of incompleteness or
      low quality. Several high-burden countries have performed TB prevalence surveys
      to obtain epidemiological information. As a standardized method for TB prevalence
      surveys has not been defined, we discuss the different options for measuring
      prevalence and their advantages and disadvantages. Most surveys use comparable
      strategies. Alternatives strategies at lower cost need to be evaluated.

PMID- 17445139
TI  - Temporal trends and epidemiological aspects of ciguatera in French Polynesia: a
      10-year analysis.
AB  - OBJECTIVES: The purpose of this study was to report the temporal trends of the
      incidence of ciguatera poisoning from 1992 to 2001 in French Polynesia. METHODS:
      This retrospective study analysed 7842 cases of ciguatera disease recorded over a
      period of 10 years. RESULTS: The annual incidence varied from 26.3 to 41.9 per
      10,000 person-years. An analysis of cases grouped by archipelago revealed
      differences in incidences (P < 0.0001) with the most remote archipelagos having
      the highest incidences. A detailed analysis on a sub-sample of recorded cases for
      which clinical information was available (n = 1824) confirmed the neurological
      and gastrointestinal nature of this seafood poisoning. CONCLUSION: The incidence
      of ciguatera poisoning appeared relatively stable during the 10 years of the
      study period. However, the gradient of remoteness observed suggests an adaptation
      of management of ciguatera disease to each archipelago.

PMID- 17445140
TI  - Clinical features and associated morbidity of scabies in a rural community in
      Alagoas, Brazil.
AB  - OBJECTIVE: To describe the clinical characteristics of scabies and the associated
      morbidity in an impoverished rural community in northeast Brazil. METHOD: A door
      to-door survey was made to examine twice the population of an endemic area; first
      at the end of the rainy season, and a second time in the dry season 4 months
      later. RESULTS: In total, 2005 individuals were examined. The overall prevalence
      of scabies was 9.8% (95% CI 8.5-11.2). Predilection sites with similar relative
      frequencies in all age groups were the abdomen (83.7%) and the inguinal
      area/inner part of the thighs (66.3%). Hands, feet, genitals and the
      scalp/neck/face were significantly more often affected in children <7 years (all
      P < 0.03). Fifty-five per cent of the patients showed scabies lesions
      simultaneously at > or = 12 distinct topographic areas. Papular lesions were most
      commonly found, followed by papular-crusted lesions. Vesicles were significantly
      more often observed in children (P = 0.04). Sixty-four per cent of the patients
      had three or more types of lesions. Local lymphadenopathy was present in 53.6%
      and superinfection in 36.7% of the cases. The number of topographic areas
      affected, as well as the proportion of superinfected lesions, was inversely
      correlated with age (rho = -0.22, P = 0.002 and rho = -0.358, P < 0.05,
      respectively). The quantity of skin surface infested, the proportion of
      superinfected lesions and the presence of a superinfected lesion distal to an
      enlarged lymphnode were predictors of lymphadenopathy. Seventy-two per cent of
      the patients suffered from sleep disorders, mainly because of itching.
      CONCLUSION: Scabies is associated with considerable morbidity in this endemic
      community. Predilection sites, clinical presentation, quantity of skin surface
      affected and proportion of secondary infected lesions show a dichotomy between
      children and adults.

PMID- 17445141
TI  - Social and environmental determinants of Aedes aegypti infestation in Central
      Havana: results of a case-control study nested in an integrated dengue
      surveillance programme in Cuba.
AB  - OBJECTIVE: To characterize the social and environmental risk factors associated
      with the presence of Aedes aegypti in order to improve community dengue control.
      METHODS: A case-control study with 'cases' being households with entomologically
      confirmed A. aegypti infestation; personal interviews in Central Havana, a
      densely populated inner city area characterized by overcrowded housing and
      irregular water service. The participants were residents of 278 houses with
      infestation and 556 houses without infestation. RESULTS: Greater risk of
      infestation was associated with lack of preventive measures, such as no larvicide
      in the water tanks (OR = 2.21) and use of flower vases for religious practice
      (1.93), not being economically active (1.64), vulnerable populations with higher
      risks in households with older people (1.52) and households with children (1.94).
      CONCLUSIONS: Efforts to reduce infestations should continue to focus on water
      tank sanitation and improving housing conditions, but also engage community
      religious leaders to help promote safe practices. Vulnerable populations should
      be especially targeted by prevention activities. A surveillance programme can
      produce evidence to guide interventions.

PMID- 17445142
TI  - Association between haemoglobin variants S and C and Mycobacterium ulcerans
      disease (Buruli ulcer): a case-control study in Benin.
AB  - Risk factors for Buruli ulcer (BU) are poorly understood. We conducted a case
      control study in southern Benin to investigate the association between
      haemoglobin variants S or C and BU, and particularly the association between
      haemoglobinopathies HbSS/SC and BU osteomyelitis. We compared the haemoglobin
      genotype of 179 patients with BU and 44 with BU osteomyelitis to that of 242
      community controls. We found no evidence of an increased risk of BU according to
      the presence of haemoglobin variants S and/or C [odds ratio adjusted for sex,
      age, region of residence and ethnicity: 1.24 (95% CI: 0.80-1.93), P = 0.34].
      Haemoglobin variants S and C are unlikely to play a role in the BU burden.
      However, haemoglobinopathies HbSS/SC were more frequent among BU osteomyelitis
      patients than among controls (6.8% vs. 1.0%, Fisher's exact P-value = 0.045),
      which may suggest that those disorders facilitate growth of Mycobacterium
      ulcerans in the bone matrix.

PMID- 17445143
TI  - Intermittent preventive treatment of malaria in pregnancy: the effect of new
      delivery approaches on access and compliance rates in Uganda.
AB  - OBJECTIVE: To assess whether traditional birth attendants, drug-shop vendors,
      community reproductive health workers and adolescent peer mobilizers can
      administer intermittent preventive treatment (IPT) with sulfadoxine-pyremethamine
      to pregnant women, and reach those most at risk of malaria and increase access
      and compliance to it. METHODS: The study was designed to assess new approaches of
      delivering IPT through these groups and compare it with IPT at health units. The
      primary outcome measures were: the proportion of adolescents and primigravidae
      accessed; gestational age at recruitment and the proportion of women who
      completed two doses of sulfadoxine-pyremethamine. RESULTS: Two thousand seven
      hundred and eighty-five pregnant women (78% of those in the study area)
      participated. With new approaches, 92.4% of the women received IPT during the
      second trimester as recommended by the policy, vs. 76.1% at health units, P <
      0.0001. Of the women who received two doses of sulfadoxine-pyremethamine, 39.9%
      were at health units (control) vs. 67.5% through new approaches (P < 0.0001).
      Women using the new approaches also accessed IPT early: the mean gestational age
      when receiving the first dose of sulfadoxine-pyremethamine was 21.0 weeks vs.
      23.1 weeks at health units (P < 0.0001). However, the health units were used by a
      higher proportion of primigravidae (23.6% vs. 20.0%, P < 0.04), and this was also
      the case for adolescents (28.4% vs. 25.0%, P < 0.03). This intervention was
      acceptable with 89.1% of the women at the new approaches intending to use IPT in
      future. CONCLUSIONS: The new approaches increased access to and compliance with
      IPT. We recommend a review of the policy to allow the provision of IPT through
      the new approaches.

PMID- 17445144
TI  - Are mosquitoes diverted from repellent-using individuals to non-users? Results of
      a field study in Bolivia.
AB  - Outside sub-Saharan Africa, Anopheline mosquito exophagic and/or crepuscular
      behaviour patterns imply that insecticide-treated nets may provide incomplete
      protection from malaria-infective mosquito bites. Supplementary repellent
      treatment has been recommended in such circumstances, especially where vectors
      are exophilic and so are not susceptible to residual insecticide spraying. As
      maintaining complete usage of repellents in a community is unrealistic, the
      potential negative impact on non-users of repellent usage by 'neighbours' in the
      same community needs to be addressed in the context of health policy promoting
      equity. This study quantifies diversion of host-seeking mosquitoes, from
      repellent wearing to unprotected individuals, 1 m apart under field conditions in
      Bolivia. Each of the six volunteer-pairs sat >20 m apart from other pairs.
      Volunteers were allocated di-ethyl toluamide (DEET) or mineral oil in ethanol
      control. Treatments were rotated, so that during the trial, both pair-members
      wore repellent on 72 occasions; both pair-members wore control on 72 occasions;
      and on 36 occasions, one pair-member wore repellent and the other control.
      Unprotected (control) pair-members received 36.4% [95% confidence interval (CI):
      8.1-72.0%] more Anopheles darlingi landings (P = 0.0096) and 20.4% (95% CI: 0.6
      44.0%) more mosquito landings (P = 0.044), when their 'partner' wore repellent
      than when their partner also wore control. A second, smaller Latin-square trial
      using 30% lemongrass (Cymbopogon citratus) repellent, with control, obtained
      26.0% (95% CI: 5.2-51.0%) more mosquito landings when controls sat with repellent
      wearers rather than other controls (P = 0.0159). With incomplete community
      repellent usage, non-users could be put at an increased risk of malaria. The
      results also have implications for repellent-efficacy assay design, as protection
      will appear magnified when mosquitoes are given a choice between repellent-users
      and non-users.

PMID- 17445145
TI  - Diagnosis and management of malaria by rural community health providers in the
      Lao People's Democratic Republic (Laos).
AB  - We assessed the knowledge of malaria diagnosis and management by community health
      providers in rural Vientiane and Savannakhet Provinces, Lao PDR. Sixty health
      providers (17 pharmacy owners/drug sellers and 43 village health volunteers) were
      interviewed. All diagnosed malaria using symptoms and signs only; 14% were aware
      of >2 criteria for the diagnosis of severe malaria. Although chloroquine and
      quinine, the then recommended Lao national policy for uncomplicated malaria
      treatment, were the most common antimalarials prescribed - 65% gave incorrect
      doses and 70% did not know the side effects. Although not recommended by the then
      national policy, 27% of the health providers used combinations of antimalarials
      as they considered monotherapy ineffective. This study strongly suggests that
      further training of Lao rural health providers in malaria diagnosis and
      management is needed to improve the quality of health services in areas remote
      from district hospitals.

PMID- 17445146
TI  - Submicroscopic Plasmodium falciparum gametocyte carriage is common in an area of
      low and seasonal transmission in Tanzania.
AB  - OBJECTIVE: Recently developed molecular gametocyte detection techniques have
      shown that submicroscopic Plasmodium falciparum gametocytes are common in
      symptomatic patients and can infect mosquitoes. The relevance for the infectious
      reservoir of malaria in the general population remains unknown. In this study, we
      investigated submicroscopic asexual parasitaemia and gametocytaemia in
      inhabitants of an area of hypoendemic and seasonal malaria in Tanzania. METHODS:
      Two cross-sectional malariometric surveys were conducted in the dry and wet
      seasons of 2005 in villages in lower Moshi, Tanzania. Finger prick blood samples
      were taken to determine the prevalence of P. falciparum parasites by microscopy,
      rapid diagnostic test and real-time nucleic acid sequence-based amplification (QT
      NASBA). RESULTS: 2752 individuals participated in the surveys, of whom 1.9%
      (51/2721) had microscopically confirmed asexual parasites and 0.4% (10/2721) had
      gametocytes. In contrast, QT-NASBA revealed that 32.5% (147/453) of the
      individuals harboured asexual parasites and 15.0% (68/453) had gametocytes. No
      age dependency or seasonality was observed in submicroscopic parasite carriage.
      DISCUSSION: Molecular detection techniques reveal that carriage of submicroscopic
      asexual parasite and gametocyte densities is relatively common in this low
      transmission area. Submicroscopic gametocytaemia is likely to be responsible for
      maintaining malarial transmission in the study area.

PMID- 17445147
TI  - Effect of costing methods on unit cost of hospital medical services.
AB  - OBJECTIVE: To explore the variance of unit costs of hospital medical services due
      to different costing methods employed in the analysis. METHODS: Retrospective and
      descriptive study at Kaengkhoi District Hospital, Saraburi Province, Thailand, in
      the fiscal year 2002. The process started with a calculation of unit costs of
      medical services as a base case. After that, the unit costs were re-calculated
      based on various methods. Finally, the variations of the results obtained from
      various methods and the base case were computed and compared. RESULTS: The total
      annualized capital cost of buildings and capital items calculated by the
      accounting-based approach (averaging the capital purchase prices throughout their
      useful life) was 13.02% lower than that calculated by the economic-based approach
      (combination of depreciation cost and interest on undepreciated portion over the
      useful life). A change of discount rate from 3% to 6% results in a 4.76% increase
      of the hospital's total annualized capital cost. When the useful life of durable
      goods was changed from 5 to 10 years, the total annualized capital cost of the
      hospital decreased by 17.28% from that of the base case. Regarding alternative
      criteria of indirect cost allocation, unit cost of medical services changed by a
      range of -6.99% to +4.05%. We explored the effect on unit cost of medical
      services in one department. Various costing methods, including departmental
      allocation methods, ranged between -85% and +32% against those of the base case.
      Based on the variation analysis, the economic-based approach was suitable for
      capital cost calculation. For the useful life of capital items, appropriate
      duration should be studied and standardized. Regarding allocation criteria,
      single-output criteria might be more efficient than the combined-output and
      complicated ones. For the departmental allocation methods, micro-costing method
      was the most suitable method at the time of study. CONCLUSIONS: These different
      costing methods should be standardized and developed as guidelines since they
      could affect implementation of the national health insurance scheme and health
      financing management.

PMID- 17445148
TI  - Fracture treatment by bonesetters in central Ghana: patients explain their
      choices and experiences.
AB  - OBJECTIVE: To understand factors influencing patients' decisions to choose either
      fracture treatment by a bonesetter or in the hospital and to explore patients'
      experiences with bonesetter treatment. METHOD: In-depth interviews with 46
      patients with a radiological proven fracture in a district hospital in central
      Ghana. RESULTS: Traditional healers, such as bonesetters, play a substantial role
      in the Ghanaian healthcare system. Over a period of 3 months, 14 patients with a
      proven fracture left hospital for treatment by a bonesetter. The hospital is
      considered the only institution where emergency care can be provided and
      reliable, extensive diagnostic and treatment facilities are available for
      fracture treatment. Patients opting for bonesetter treatment are guided by the
      severity of the fracture, availability of the service, their financial status and
      past experiences. The healing methods used by different bonesetters are based on
      mutual comparable principles. CONCLUSION: Fracture treatment can serve as a model
      for respectful and efficient co-existence of traditional and biomedical medicine.

PMID- 17445151
TI  - Overview of registries, HLA typing and diversity, and search algorithms.
AB  - Over 10 million volunteer donors and cord blood units are typed for human
      leukocyte antigen (HLA) within hematopoietic stem cell registries and cord blood
      banks. Identification of matched donors in countries different from that of the
      searching patient is facilitated by Bone Marrow Donors Worldwide and the World
      Marrow Donor Association (WMDA). A survey of new volunteer donor typing among
      WMDA member registries has identified the methods and resolution of HLA testing
      and the level of quality control used to evaluate the accuracy of typing results.
      The diversity of HLA assignments within registries has generated a number of
      informatics challenges. Registries are using population genetics to enhance
      registry diversity and to facilitate the identification of matched donors.

PMID- 17445152
TI  - Strategies for typing new volunteer donors.
AB  - Unrelated donor registries use a variety of strategies for human leukocyte
      antigen typing newly recruited volunteers and for prospective typing and file
      maintenance projects. The approaches change over time with respect to the level
      of resolution and loci tested based on costs, advances in technologies and
      emerging clinical outcome data from matching studies.

PMID- 17445153
TI  - Strategies for new donor typing based on donor HLA type or donor characteristics.
AB  - Registries of volunteer unrelated haematopoietic stem cell donors must make
      decisions on the procedures used to human leukocyte antigen type new donors based
      on various factors including available finances and donor diversity. This
      manuscript describes a comparison of new donor typing strategies for three
      European registries which was presented for discussion at the 14th International
      Histocompatibility Workshop.

PMID- 17445154
TI  - Typing of potential and selected donors for transplant: methodology and
      resolution.
AB  - The goal was to establish the best typing techniques and strategies for donors
      selected as potential donors for a specific patient. Complete sequence of exons 2
      and 3 for class I and exon 2 for class II molecules by sequencing-based typing
      was deemed the best technique in reducing problems with ambiguities and null
      alleles as well as the possibility to establish a completely automated system.
      Focusing on multiple approaches for typing was regarded as a better strategy than
      continued usage of serological methods although the latter technique was still
      considered to be useful by some for detection of null alleles. The patient and
      finally the selected donor, including the back-up donor, should be typed for at
      the highest level and typing ambiguities should be resolved. In very difficult
      cases, race, haplotype information and allele frequency in the population should
      help to decide whether or not to resolve the ambiguity. Cellular techniques such
      as the cytotoxic T lymphocyte precursor test may help to choose between single
      class I mismatched donors in experienced laboratories only.

PMID- 17445155
TI  - Quality control for registry HLA data.
AB  - In this panel discussion, the following issues were addressed: the evaluation of
      the quality of the volunteer donors human leukocyte antigen (HLA) assignments,
      the quality criteria that should be met by the laboratories, the source of
      errors, the measures that registries can take to assess the quality of HLA
      testing, and the updating of the initial result with emphasis on resolution of
      typing discrepancies. Several relevant factors were put forward: the need for the
      registries to define the HLA loci and the level of resolution requested, and the
      importance of the accreditation programs with adequate external proficiency
      testing. The feasibility of annual quality controls of a national registry
      addressing the limitations of HLA class I serology, and the rules set up by a
      large registry to incorporate new data on donors HLA types and to rapidly track
      typing discrepancies, were reported.

PMID- 17445156
TI  - Improving communication among the HLA typing laboratories, transplant centers,
      and coordinating center.
AB  - Good communication between the bone marrow registries, the donor centres, tissue
      typing laboratories and clinical units is paramount to ensure timely
      identification, testing and selection of donors for unrelated bone marrow
      transplants. This panel session focussed on how to improve communication so that
      there was a clear understanding of prioritization of requests from clinicians,
      typing strategies in the laboratories and requests for donors to the registries.
      This paper outlined some of the strategies discussed in this session.

PMID- 17445157
TI  - 14thInternational HLA and Immunogenetics Workshop: report on hematopoietic cell
      transplantation.
AB  - Deciphering the role of human leukocyte antigen (HLA), killer immunoglobulin like
      receptor, and immune response genes in a model as complex as unrelated donor
      hematopoietic cell transplantation is a challenge. The allelic diversity of these
      genes is shaped by the race and ethnicity of transplant donors and recipients.
      Coupled with the genetic polymorphism is the complexity of clinical phenotypes of
      transplant populations: donor and recipient demographic characteristics and the
      regimens used by transplant physicians to prepare patients for transplantation
      and to prevent and treat graft-vs-host disease (GVHD). Furthermore, GVHD is
      itself a complex disease shaped by both genes and 'environment'. How does one
      begin to deconstruct the genetic barrier to understand risk factors important to
      transplant outcome? To begin with, population-based studies, particularly
      retrospective ones, benefit from adequate sample sizes to measure genetic
      effects. The more homogeneous the population for variables that influence
      clinical endpoints, the higher the likelihood that a real genetic effect can be
      uncovered. Even so, the feasibility of studies can be hampered if genotype and
      clinical data are not both complete and precise. For studies of HLA, diversity of
      alleles and antigens contributed by ethnically different transplant populations
      is an asset, because not only can a broader range of HLA mismatches be studied
      but they provide the opportunity for side-by-side analyses that may yield clues
      as to why transplant outcomes differ between populations.

PMID- 17445158
TI  - Clinical significance of donor-recipient HLA matching on survival after
      myeloablative hematopoietic cell transplantation from unrelated donors.
AB  - The application of unrelated donor hematopoietic cell transplantation can be
      expanded with the use of mismatched donors if human leukocyte antigen (HLA)
      disparity does not lead to increased morbidity and mortality. The rules that
      govern permissibility of HLA mismatches are not well defined. The International
      Histocompatibility Working Group in hematopoietic cell transplantation measured
      the risks associated with locus-specific disparity in 4796 patients transplanted
      for low, intermediate, or high-risk hematologic diseases. The permissibility of a
      given HLA mismatch is in part defined by the locus and by disease risk.

PMID- 17445159
TI  - Effect of HLA-A2 allele disparity on clinical outcome in hematopoietic cell
      transplantation from unrelated donors.
AB  - Population-based differences in clinical outcome after unrelated donor
      hematopoietic cell transplantation suggest that the significance of human
      leukocyte antigen (HLA) mismatching may be related to locus-specific and allele
      specific differences that distinguish ethnically diverse transplant donors and
      recipients. We studied the risks associated with HLA-A locus mismatching in two
      large transplant populations from the International Histocompatibility Working
      Group in hematopoietic cell transplantation data set to better understand
      permissible and nonpermissible HLA-A mismatches.

PMID- 17445160
TI  - Clinical importance of HLA-DPB1 in haematopoietic cell transplantation.
AB  - There is increasing evidence for a significant effect of human leukocyte antigen
      (HLA)-DPB1 mismatching on complications following unrelated donor haematopoietic
      cell transplantation (HCT). In this analysis of 5930 patient/donor pairs, we
      found that a DPB1 mismatch predicted significantly for an increased risk of acute
      graft-vs-host disease [hazard ratio (HR): 1.33; P-value = <0.0001], while
      protecting against disease relapse (HR: 0.82, P-value = 0.01). These data support
      an immunogenic role for HLA-DPB1 in HCT and the need for pretransplant tissue
      typing at this locus.

PMID- 17445161
TI  - Hematopoietic stem cell transplantation: killer immunoglobulin-like receptor
      component.
AB  - Recognition of recipient human leukocyte antigen (HLA) class I ligand by donor
      natural killer cell killer immunoglobulin-like receptors (KIR) has been proposed
      as the basis for donor allograft reactivity against malignancy leading to
      reduction in posttransplant relapse and higher survival for acute myelogenous
      leukemia. Analysis of KIR ligand effects in 1770 patients undergoing
      myeloablative T-replete hematopoietic cell transplantation (HCT) from HLA-matched
      or mismatched unrelated donors showed that lack of KIR ligand in patients for
      inhibitory KIR was associated with lower hazards of relapse in leukemia patients
      with in HLA-mismatched transplants [hazard ratio (HR): 0.061; 95% confidence
      interval (CI): 0.43-0.85; P-value = 0.004]. Absence of HLA-C group 2 or HLA-Bw4
      KIR ligands were each associated with lower hazards of relapse (HR: 0.47; 95% CI:
      0.28-0.79; P-value = 0.004; HR: 0.56; 95% CI: 0.33-0.97; P-value = 0.04,
      respectively). Based on these analyses, recipient homozygosity for HLA-B or -C
      epitopes that define KIR ligands is likely to be a predictive factor for leukemia
      relapse following myeloablative HCT from unrelated donors. KIR genotyping for
      unrelated donors and recipients will clarify the role of these receptors in
      transplant outcome.

PMID- 17445162
TI  - MHC class I, II, and III microsatellite marker matching and survival in unrelated
      donor hematopoietic cell transplantation.
AB  - Microsatellites (Msats) are effective markers for disease association mapping.
      The International Histocompatibility Working Group in hematopoietic cell
      transplantation applied Msats to determine whether potential new transplantation
      determinants are encoded within the major histocompatibility complex.
      Retrospective analysis of human leukocyte antigen-identical unrelated donor
      transplants provided a homogeneous population to measure Msat-associated risks of
      mortality.

PMID- 17445163
TI  - Immune response gene polymorphisms in unrelated donor hematopoietic cell
      transplantation.
AB  - Immune response genes (IRG) play an important role in inflammation and control of
      infection after allogeneic transplantation. The International Histocompatibility
      Working Group (IHWG) in hematopoietic cell transplantation took a candidate gene
      approach to define the risks associated with genetic variation for a panel of
      well-characterized IRG.

PMID- 17445164
TI  - 14th International HLA and Immunogenetics Workshop: report from the sequencing
      based typing group.
AB  - Sequencing-Based Typing (SBT) provides the golden standard for the identification
      of polymorphism among the human leukocyte antigen (HLA) alleles. Several SBT
      approaches have been published. Updated protocols for HLA-DRB and -DQB were
      presented and an approach for DQA, covering all exons, validated. The highest
      level of allele typing can be realized with strategies for resolving allele and
      genotype ambiguities. Bioinformatics provides the tools for exchange and sharing
      data with a community standard in XML format.

PMID- 17445165
TI  - Sequencing-based typing identifies novel alleles due to single nucleotide
      polymorphisms in 'conserved' regions.
AB  - The Royal Perth Hospital laboratory has been using sequencing-based typing for
      all HLA loci since 2002. In the period to October 2005, approximately 12,000 HLA
      A and HLA B, 5000 HLA C and DQB1, and 17,000 DRB1 requests have been processed.
      Twenty nine novel alleles have been identified in that time. These comprise 10
      HLA-A (including one null allele), five HLA-B, six HLA-C, six DRB1 (including a
      null allele), and one DQB1 novel allele. (At the time of identifying the DRB1
      null allele, there were no other reported examples.) In addition, we have seen
      one example of a blast-specific HLA-A null allele. One HLA-A allele (HLA-A*0264)
      and one HLA-B allele (HLA-B*400104) were subsequently identified in other
      laboratories and submitted to the international ImMunoGeneTics project (IMGT)
      database.

PMID- 17445166
TI  - The identification and characterisation of a novel null HLA-DRB1 allele.
AB  - Since the introduction of DNA-based human leukocyte antigen (HLA) typing a number
      of discrepancies with serological typing have been documented. At the time of
      submission of this abstract (July 2005 ImMunoGeneTics project (IMGT) project
      database release) 42 HLA class I and II null alleles had been described
      characterised by a lack of expression of cell surface antigen. These null alleles
      can be accounted for by a number of demonstrated molecular mechanisms including
      insertion, deletion and point mutation and may lead to a nonsense codon, splicing
      defect or premature stop codon.

PMID- 17445167
TI  - HLA-DRB sequencing-based typing: an improved protocol which shows complete DRB
      exon 2 sequences and includes exon 3 of HLA-DRB4/5.
AB  - Several human leukocyte antigen (HLA)-DRB protocols for sequencing-based typing
      have been described. In general, the DRB1 amplification is performed using group
      specific amplification primers (GSAPs) located in HVR I or intron 1. Only some
      protocols include amplification of DRB3, DRB4, and DRB5. However, prior knowledge
      obtained by alternative methods such as PCR-SSP is preferred for some protocols
      and a large amount of DNA is often required for adequate typing of HLA-DRB1. We
      describe a new protocol that uses GSAPs located in the introns, includes also
      sequencing of exon 3 to enable high resolution. This protocol allows DRB typing
      without prior knowledge of the HLA type.

PMID- 17445168
TI  - HLA-DQB1 sequencing-based typing updated.
AB  - The use of direct sequencing as a typing strategy is well acknowledged. Direct
      sequencing identifies all sequence motifs including new polymorphisms in
      heterozygous sequences. The earlier protocols for human leukocyte antigen HLA
      DQB1 Sequencing-Based Typing (SBT) frequently encounter preferential
      amplification of one of the alleles that can lead to unreliable sequences or even
      to allelic dropout. In our new approach, the quality of the exon 2 sequences, now
      including both alleles to the same extend, was achieved by amplifying the HLA
      DQB1*05/06 group into two groups by changing the common 3' amplification primer.
      In combination with exon 3 this updated HLA-DQB1 protocol provides a reliable
      approach for heterozygous sequencing.

PMID- 17445169
TI  - Pilot study: assessment of interlaboratory variability of sequencing-based typing
      DNA sequence data quality.
AB  - This pilot study showed that variability in the sequence quality scores exists
      within and between laboratories performing human leukocyte antigen typing by
      sequence-based typing (SBT). It also showed that the base call score (BCS) system
      in Assign-SBT is a useful tool for comparing sequence quality between
      laboratories.

PMID- 17445170
TI  - A community standard XML message format for sequencing-based typing data.
AB  - An electronic messaging format has been developed and is proposed as a community
      standard. This format allows explicit representation of typing results for
      polymorphic immunogenetic gene systems such as killer cell immunoglobulin-like
      receptor and human leukocyte antigen. Primary data in the form of Sequence
      Specific Oligonucleotide (SSO)/Sequence Specific Primer (SSP) reactivities and
      sequencing-based typing sequences can be linked with nomenclature-based results
      allowing complete representation of the permanent information.

PMID- 17445171
TI  - The common marmoset as a novel preclinical transplant model: identification of
      new MHC class II DRB alleles and prediction of in vitro alloreactivity.
AB  - The difficulties with using nonhuman primate species such as rhesus macaques and
      baboons have led us to investigate the common marmoset (Callithrix jacchus) as an
      alternative preclinical model for transplantation research. This requires
      reliable methods of detecting alloreactivity between donor and recipient pairs,
      particularly if colonies are inbred and share just a few common alleles for
      leucocyte antigens. We firstly identified marmoset major histocompatibility
      complex (MHC) Class II DRB genes (Caja-DRB*W1201, Caja-DRB1*03, Caja-DRB*W16)
      using sequence-based typing techniques. Genomic DNA (n= 49) was extracted from
      whole blood or spleen tissue. Exon 2 of target genes was amplified by PCR using
      primers specific for known marmoset alleles, and then sequenced using ABI
      PRISM((R)) Big Dye Terminator technology and Assign sequence analysis software.
      DRB*W1201 was universally present. Eight DRB*W16 alleles and five DRB1*03 alleles
      were identified in this colony. We also identified two previously unreported
      DRB*W16 alleles, and confirmed inheritance of these alleles within several
      sibling groups. Subsequently, we investigated whether matching at MHC Class II
      DRB loci alone could predict alloreactivity, as assessed in vitro by two-way
      mixed lymphocyte reactions (MLRs). Fully DRB-matched, partially mismatched and
      fully mismatched animal pairs were prospectively chosen. MLR was performed using
      mononuclear cells (MNC) isolated from whole blood by density gradient separation.
      T-cell proliferation after 5-day culture was measured by (3)H-thymidine
      incorporation. Combined MNC from fully mismatched and partially mismatched animal
      pairs exhibited significant in vitro T-cell proliferation above single cell
      controls (P < 0.01). MNC from fully DRB-matched (but unrelated) animal pairs
      exhibited no proliferation compared with controls (P= 0.3). Using DRB genotyping,
      suitably alloreactive donor-recipient pairs may therefore be rapidly and
      accurately identified for use in further studies of cellular and solid organ
      transplantation.

PMID- 17445172
TI  - Sequence-based typing of HLA-DQA1: comprehensive approach showed molecular
      heterogeneity.
AB  - Within the human leukocyte antigen-DQA1 workshop project the level of molecular
      heterogeneity of the DQA1 gene was investigated. An improved sequence-based
      typing protocol was used, enabling analysis of the complete coding sequence,
      comprising exons 1-4. The participating laboratories implemented the
      amplification and sequencing primers in their own sequence-based typing approach.
      The method proved to be sufficiently robust to handle the differences in
      protocols. All reference samples used for validation were correctly typed for
      DQA1 by all participating laboratories. Three different populations with a total
      of 736 individuals were investigated: a population of Korean origin (n= 467), a
      British Caucasian (n= 114), and a Dutch Caucasian (n= 155) population. Sixteen of
      the known 28 DQA1 alleles were detected and six new alleles were identified. All
      novel alleles showed a nucleotide substitution outside exon 2. Comparison of the
      calculated allele frequencies revealed major differences between the Korean and
      the Caucasian populations but also between Dutch and British Caucasians. A tight
      association between DQA1 and DRB1/DQB1 alleles was observed in all three
      populations.

PMID- 17445173
TI  - Diversity of HLA-DQA1 gene in the Korean population.
AB  - Genotype of the human leukocyte antigen (HLA)-DQA1 locus was analyzed in Koreans
      (n= 467) using the 14th International Workshop protocol established to
      characterize the sequences of exons 1-4 of the gene. Unexpectedly, it appeared
      that the DQA1 (19 alleles) was more diverse than DQB1 (15 alleles) in the study
      population. DQA1*010201, DQA1*0303, DQA1*0103, and DQA1*0302 appeared to be major
      alleles exhibiting more than 10%. Among six allele groups, DQA1*01-*06, DQA1*01
      showed highest diversity exhibiting seven different alleles. Analysis using
      maximum likelihood method showed numerous multi-locus HLA haplotypes. High
      relative linkage disequilibrium values (RLD) of the two-locus haplotypes and
      exclusive association of a specific DQA1 allele with a specific DRB1 and/or DQB1
      alleles suggested tight linkage of DQA1 to DRB1 and DQB1. In HLA-matching process
      for hematopoietic stem cell transplantation, however, DQA1 typing would be
      informative for individuals carrying specific DRB1 allele (DRB1*0802, DRB1*1201,
      or DRB1*1403) that could be associated with multiple DQA1 alleles in the study
      population. Information obtained in this study will be useful in medical and
      forensic areas as well as in anthropology.

PMID- 17445174
TI  - 14th International HLA and Immunogenetics Workshop: report on KIR receptors and
      their applications.
AB  - During the last few years many laboratories have developed a keen interest in
      detecting killer immunoglobulin-like receptor (KIR) receptor genes in various
      populations, diseases and in stem cell transplantation. At the 14th International
      Histocompatibility Workshop held in Melbourne in December 2006, many of these
      laboratories presented their findings at a special session. To introduce this
      work, we provide an introduction to KIR receptors and an outline of previous
      applications of KIR receptor typing prior to the Workshop.

PMID- 17445175
TI  - Cloning and sequencing alleles of the KIR2DL4 gene from genomic DNA samples.
AB  - Killer-cell immunoglobulin-like receptor (KIR) genes are highly polymorphic and
      polymorphisms have been found in all KIR exons. Although less is known of the
      introns, these also appear to be polymorphic. To generate a comprehensive
      database of KIR genomic sequences, which will aid in the design of KIR typing
      reagents, we have established a method for cloning and sequencing of KIR genes
      from genomic DNA. We cloned and sequenced the entire KIR2DL4 gene from genomic
      DNA using long template touchdown PCR and high capacity cloning vectors.
      Overlapping secondary amplicons were modified to include a nucleotide analogue
      that reduced sequencing problems associated with secondary structure formation in
      the KIR sequence. Using a modified sequencing chemistry we were able to sequence
      approximately 11,000 bases confirming the previously published KIR2DL4*005 allele
      sequence.

PMID- 17445176
TI  - KIR genotyping by reverse sequence-specific oligonucleotide methodology.
AB  - Recent studies suggest that killer cell immunoglobulin-like receptors (KIR)
      genotyping may be relevant to bone marrow/stem cell transplantation. The
      objective of this research was to develop a bead-based reverse sequence-specific
      oligonucleotide DNA hybridization assay for KIR genotyping using the Luminex
      platform. The oligonucleotide probes were designed to recognize 14 currently
      known KIR genes and two pseudogenes, as well as null alleles. A unique probe
      design was used to allow detection of two cis-polymorphic regions for typing of
      KIR2DS4, because the functioning alleles cannot readily be assigned by
      conventional probe detection systems. Assay performance was validated using DNA
      samples previously typed by the 13th International Histocompatibility Working
      Group with 100% concordant results.

PMID- 17445177
TI  - Preliminary analysis of a KIR haplotype estimation algorithm: a simulation study.
AB  - The analysis of Killer cell immunoglobulin-like receptors (KIRs) in terms of
      haplotypes have only been done through genotyping numerous and selected families.
      Consequently and schematically, KIR haplotypes have been roughly described by two
      groups (A and B) based on their gene contents. No further KIR adapted methods
      have been applied to the estimation of haplotype frequencies using unrelated
      data. We propose here a maximum likelihood (ML) estimation of KIR haplotype
      frequencies. ML estimation was developed as an extension of those successfully
      applied to human leukocyte antigen (HLA) data including the handling of missing
      values and HLA nomenclature. It has been implemented using an adapted Expectation
      Masimisation algorithm. KIR types on 11 loci in more than 40 Irish families were
      used to validate the method in a simulation study. Estimated haplotype
      frequencies are compared to the phase known. Various allele or gene frequency
      estimation methods were also compared. We demonstrated the interest and
      reliability of the haplotype method and underline the effect of the sample size
      on the quality of the estimation. The ML haplotype method also provides by
      collapsing more accurate estimation of allele or gene frequencies in population.
      Such an algorithm opens new perspectives in the analysis of KIR genotypes. Large
      sample size studies are required using phase-known data and/or simulations. It
      would allow a genotype-based approach to explore the KIR gene haplotype
      diversity. The haplotype frequencies may be used to compare populations.

PMID- 17445178
TI  - Modelling KIR-HLA genotype disparities in type 1 diabetes.
AB  - We previously reported that a disparate distribution between killer cell
      immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) class 1
      genes is associated with susceptibility to develop type 1 diabetes. Here we
      compare multiple models which reflect the combined genotype effects of
      combinations of functional inhibitory and activating KIRs in relation to HLA in
      an extended cohort of patients with juvenile-onset type 1 diabetes and non
      diabetic control subjects. Our results suggest that autoimmunity in type 1
      diabetes is mainly associated with a decrease in inhibitory KIR-HLA genotype
      combinations, while the influence of activating KIR genotypes seems redundant.
      However, logistic regression showed that activating KIR genotypes do influence
      the overall hierarchy of protection/susceptibility as reflected by composite
      inhibitory and activating KIR-HLA genotype models.

PMID- 17445179
TI  - KIRs and autoimmune disease: studies in systemic lupus erythematosus and
      scleroderma.
AB  - We investigated killer immunoglobulin-like receptors (KIRs) and the human
      leukocyte antigen (HLA)-C ligands for the corresponding inhibitory KIRs in
      Caucasian patients, 304 with systemic lupus erythematosus (SLE) and 90 with
      scleroderma [or progressive systemic sclerosis (PSS)] compared with 416 Caucasian
      controls. Compared with controls, KIR2DS1 in the absence of KIR2DS2 was increased
      in both SLE (P= 0.04) and PSS (P= 0.02). Only 42% of KIR2DS1-positive PSS
      patients had the appropriate HLA-C ligand for the corresponding inhibitory KIR
      compared with 61% of KIR2DS1 positive controls (P= 0.02). In the PSS group the
      presence of at least either activating KIR2DS1 and/or 2DS2 was significantly
      increased in patients when compared with controls (P= 0.001). This suggests that
      KIR receptors play a role in susceptibility to both PSS and SLE.

PMID- 17445180
TI  - Increased frequencies of activating natural killer receptors are associated with
      liver injury in individuals who do not eliminate hepatitis C virus.
AB  - This study was designed to investigate the role of killer immunoglobulin-like
      receptor (KIR) genes in the outcome of hepatitis C virus (HCV) infection. In
      patients who cleared the virus (HCV RNA-) we found a decrease of 2DL2 (P= 0.04),
      and 2DS2 (P= 0.014) accompanied by an increase of 2DS5 (P= 0.04). Those RNA+
      patients with elevated levels of hepatic transaminases (HCV RNA+ elevated alanine
      aminotransferase) showed an increased frequency of 2DS3 (P= 0.018). Additionally,
      in cirrhotic patients we found an increased frequency of individuals having two
      copies of 3DS1 and HLA-Bw4 (P= 0.016). We conclude that higher natural killer
      cytotoxicity might be associated with a worse progression of the HCV infection.

PMID- 17445181
TI  - KIR receptors and HLA-C in the maintenance of pregnancy.
AB  - The present study demonstrated that patients who have recurrent spontaneous
      abortions (RSA) presented a decreased number of killer immunoglobulin-like
      inhibitory receptors (KIR), in particular KIR2DL2. The KIR AA genotype was found
      increased in comparison with controls. Individuals AA will also be homozygous for
      2DL3, which in contrast to 2DL2, show a weaker interaction with C1 ligands and
      therefore a weaker inhibition. The present study might support that in RSA
      patients, the balance between inhibitory and activating receptors present in
      natural killer cells is inclined toward an activating state that may contribute
      to pregnancy loss.

PMID- 17445182
TI  - Influence of killer cell immunoglobulin-like receptor genotypes on acute graft-vs
      host disease after unrelated hematopoietic stem cell transplantation in Koreans.
AB  - Interactions between killer cell immunoglobulin-like receptors (KIRs) and human
      leukocyte antigen class I ligands influence the development of the natural killer
      cell repertoire and the responses to infection, cancer, and allogeneic tissue. In
      this study, the association of KIR genes with acute graft-vs-host disease (GVHD)
      was investigated in 44 pairs of leukemia patients and their unrelated donors for
      hematopoietic stem cell transplantation (HSCT). Donors with more than 12 KIR
      genes showed significantly decreased frequencies of severe acute GVHD compared
      with donors with less than 11 KIR genes (P < 0.05). The distribution of KIR
      genotypes was not different between severe and mild acute GVHD in patients and
      donors, respectively. These results suggest that the number of KIR genes in
      donors could influence the occurrence of acute GVHD after unrelated HSCT.

PMID- 17445183
TI  - Relevance of KIR gene matching in unrelated hematopoietic stem cell
      transplantations.
AB  - The aim of this collaborative study was to evaluate the impact of killer cell
      immunoglobulin-like receptor (KIR) gene disparities on unrelated hematopoietic
      stem cell transplantations (HSCT) outcome. To address this question, we have
      determined the presence or absence of 14 functional KIR genes in HLA-matched (n=
      164) or HLA-mismatched (n= 100) donor/recipient pairs and investigated whether
      KIR gene disparities had an impact on both the occurrence of acute graft-vs-host
      disease incidence and overall survival. In a univariate analysis, our preliminary
      results suggest a detrimental effect of a few KIR gene disparities on patient
      survival that should be avoided in unrelated HSCT.

PMID- 17445184
TI  - Killer cell immunoglobulin-like receptor polymorphisms in HLA-identical kidney
      transplant recipients: lack of 2DL2 and 2DS2 may be associated with poor graft
      function.
AB  - Killer cell immunoglobulin-like receptors (KIR) on natural killer cells mediate
      killing by recognizing class I presentation of peptides by infected or oncogenic
      cells. KIR differences in stem cell transplants have been implicated in increased
      graft vs host disease. Human leukocyte antigen (HLA)-matched-related kidney
      recipients have the best graft survival as compared to one haplotype-matched
      recipients. These HLA-identical transplant pairs may be ideal for studying minor
      HLA antigens and KIR polymorphic differences and their relation to graft
      function. We have studied KIR polymorphism in recipients and donor pairs of HLA
      matched sibling kidney transplants to demonstrate differences in genotype as
      related to long-term graft function and/or chronic rejection. We employed a KIR
      genotyping kit (Dynal, Brown Deer, WI), that uses sequence-specific priming by
      PCR to identify 19 alleles for genotypes in 12 donor/recipient (D/R) pairs at
      least 1 year posttransplant. There were two pairs that had different alleles in
      the recipient that were not found in the donor. One pair had different alleles
      found in the donor that were not present in the recipient. Two pairs had
      difference in alleles in both the donor and recipient. Seven of the 12 pairs had
      the same KIR genotype. Eight of the 12 pairs (both donor and recipient) exhibited
      a haplotype with 2DL2+ and 2DS2+. Four of the 12 exhibited a haplotype 2DL2- and
      2DS2-. Three out of four of these recipients had increased creatinine levels and
      at least one graded rejection episode. One of these three has lost their graft.
      In conclusion, the genotyping of HLA-matched sibling kidney transplant D/R pairs
      demonstrates that there may be an association of higher risk for poor graft
      function when both genotypes lack 2DL2 and 2DS2.

PMID- 17445185
TI  - Distribution of the killer cell immunoglobulin-like receptors in Mexican
      Mestizos.
AB  - Understanding the complex interaction between human leukocyte antigen (HLA) and
      killer immunoglobulin-like receptor (KIR) requires study of both HLA and KIR
      diversity in the same population. The presence of KIR genes 2DL1, 2, 3, 4, 5,
      KIR3DL1, 3DL2, 3DL3, KIR2DS1, 2DS2, 2DS3, 2DS4, 2DS5, KIR3DS1, KIR3DP1, KIR2DP1
      was determined in 54 unrelated Mexican Mestizo donors. The PCR sequence-specific
      oligonucleotide probe One Lambda kit (Luminex) kindly given by J. Lee was used
      for typing. The software analyses the combination obtained for each of the five
      exons. Five controls (UCLA DNA exchange) were run as quality control. The gene
      frequency (GF) was calculated for the 16 KIR loci; the GF of individual genes was
      100% for 2DL4, 3DL1, 3DL2, 3DL3, 3DP1. KIR2DL1 (76.43%), KIR2DL2 (37.64%),
      KIR2DL3 (76.43%), KIR2DL5 (29.29%), KIR3DS1 (23.02%), KIR2DS1 (21.83%), KIR2DS2
      (37.64%), KIR2DS3 (50.93%), KIR2DS4 (86.93%), KIR2DS5 (29.29%), KIR2DP1 (86.39%).
      We observed similar frequencies with Caucasians and Mediterraneans, with
      exceptions: KIR3DL1 which was present in 100% Mexicans, ranged from 62% to 75% in
      Caucasians; 2DS3 (50.9%) vs 14-20% 2DS4 (86.39%) vs 65-79% and 2DS5 (29.29%) vs
      11-18% in Caucasians. The finding of 23 phenotypes in 54 individuals accounting
      for both chromosomes, demonstrates the enormous diversity. We found 14 different
      combinations of stimulatory KIRs in the phenotypes; every subject had at least
      one stimulatory KIR; in all of them, 2DS4 existed except for one person who may
      have some new combination: 2DS2 2DS3. Extended family data will offer accurate
      and precise haplotypes to provide an insight on the significance of ethnic
      distribution and KIR repertoire.

PMID- 17445186
TI  - 14th International HLA and Immunogenetics Workshop: report on non-classical class
      I genes.
AB  - Non-classical class I genes are encoding for cell surface proteins that have
      largely yet unknown functions. Although some of these proteins (human leukocyte
      antigens E, F and G) have been shown to present peptides, their polymorphism is
      very restricted at the peptide-binding region. In the present Workshop, several
      papers were presented addressing detection, evolutive and functional issues of
      these proteins. The general inhibitory immunological function of these proteins
      is put forward.

PMID- 17445187
TI  - HLA-E polymorphism in Amerindians from Mexico (Mazatecans), Colombia (Wayu) and
      Chile (Mapuches): evolution of MHC-E gene.
AB  - Human leukocyte antigen (HLA)-E is a nonclassical class I (Ib) gene with a
      restricted polymorphism. Only eight DNA alleles and three proteins of this gene
      have been described and their frequencies analyzed in Caucasian, Oriental, Asian
      Indian, and Negroid populations. In the present study, HLA-E polymorphism has
      been analyzed in six Amerindian and Mestizo populations from North and South
      America and compared with previously described populations. HLA-E*0101 is the
      most frequent allele found in all populations except in Afrocolombian and Wayu
      Amerindians, in which blood group analyses show a high admixture with Caucasian
      and African populations. Mazatecan and Mapuche (two Amerindian groups from North
      and South America, respectively) presented similar HLA-E frequencies, whereas
      Wayu Indians are more similar to the Afrocolombian population. The Mexican and
      Colombian Mestizo show similar allele frequencies to Amerindians with high
      frequencies of HLA-E*0101 and HLA-E*010302 alleles. Also, frequencies in Negroids
      and Asian Indians present a similar distribution of HLA-E alleles. These data are
      in agreement with worldwide restricted polymorphism of HLA-E because no new
      allele was detected in the six populations studied. The allelic frequencies show
      differences among Caucasian, Oriental, Mestizo and Indian populations. Ape major
      histocompatibility complex-E allelism is also very restricted: common chimpanzee
      (one allele); bonobo (two alleles); gorilla (two alleles); orangutan (one
      allele); rhesus monkey (eight alleles); cynomolgus monkey (two alleles); and
      green monkey (two alleles).

PMID- 17445188
TI  - MHC-F polymorphism and evolution.
AB  - The major histocompatibility complex (MHC)-F class Ib locus shows a limited
      polymorphism, and the function of its mainly intracellular protein is not clear.
      We have identified human leukocyte antigen (HLA)-F orthologous DNA sequences in
      Pongidae in order to study the MHC-F gene evolution and its products' function.
      HLA-F orthologous complementary DNA transcripts are found in chimpanzee and in
      the new primate species studied (bonobo, gorilla and orangutan). Analyses of the
      predicted amino acid sequences and their comparison with other primate MHC-F
      proteins show that MHC-F may be a protein with a typical class I structure and
      that the key residues of the peptide-binding region are highly conserved in MHC-F
      in all studied primates species. Thus, MHC-F conservation along the primate
      evolution suggests an important role in cellular physiology. It is possible that
      the MHC-F protein could be involved, together with MHC-G and MHC-E, in the
      natural killer cell activity regulation, although rhesus macaque cannot express
      complete surface MHC-G orthologue molecules.

PMID- 17445189
TI  - HLA-G levels in serum and plasma.
AB  - Soluble human leukocyte antigen (HLA)-G levels are in most cases higher in the
      plasma than in the serum obtained from the same individual. This is probably due
      to trapping of the protein during clot formation. In studies where soluble HLA-G
      is quantified, it is therefore recommended that plasma or serum levels should be
      compared with the same blood product, namely, serum to serum and plasma to
      plasma. Because of possible gender differences in HLA-G levels it is also
      recommended that this should be considered in the construction of a control group
      especially in studies where there is a preponderance of one of the sexes.

PMID- 17445190
TI  - Quantification and identification of soluble HLA-G isoforms.
AB  - In order to clarify the diagnostic relevance of soluble human leukocyte antigen-G
      (sHLA-G) molecules, reliable methods for the measurement of sHLA-G in various
      body fluids are of interest. Therefore, the aims of the 'Wet-Workshop for
      Quantification of Soluble HLA-G' held in Essen, Germany (at the Institute of
      Immunology, 18-20 October 2004) were to select and to validate HLA-G-specific
      enzyme-linked immunosorbent assay (ELISA) formats and purified standard HLA-G
      proteins, which can be easily generated and used as consensual references. We
      chose two ELISA formats, one for the simultaneous determination of shed HLA-G1 +
      sHLA-G5 (sHLA-G1 + G5) and one for the exclusive detection of HLA-G5 molecules.
      The first ELISA uses the antibody pair monoclonal antibody (mAb) MEM-G/9 + anti
      beta2-microglobulin (beta2m), whereas the latter uses mAbs 5A6G7 + W6/32.
      Purified and well-defined HLA-G5 protein derived from insect SF9 cells
      transfected with HLA-G5 + human beta2m served as standard reagent. Twenty-five
      members of 13 international laboratories participated in the 3-day Wet-Workshop.
      The workshop demonstrated that the HLA-G5 protein was equally detected by both
      ELISA formats allowing direct comparison of quantitative results obtained by
      these two ELISA formats, and that sHLA-G1 + G5 and HLA-G5 molecules,
      respectively, were specifically and reproducibly quantified by the two ELISA
      formats. The comparison of the two ELISA results obtained allows the conclusion
      that sHLA-G1 and HLA-G5 molecules can exist in the blood of healthy donors.
      Moreover, there was evidence for a novel soluble HLA-G structure recognized by
      the mAbs 5A6G7 + W6/32 antibody combination but not by the one of mAb MEM-G/9 +
      anti-beta2m.

PMID- 17445191
TI  - Functions of HLA-G in the immune system.
AB  - Human leukocyte antigen (HLA)-G is a nonclassical HLA class I molecule that has
      tolerogenic functions and acts on cells of both innate and adaptive immunity. The
      molecular mechanism leading to tolerance involves the interaction between HLA-G
      and inhibitory receptors that are expressed at the surface of immune cells. In
      this review, we will briefly summarize the key advances on the relationships
      between HLA-G and the immune system and their consequences in pathology.

PMID- 17445192
TI  - Recurrent spontaneous abortions patients have more -14 bp/+14 bp heterozygotes in
      the 3'UT region of the HLA-G gene in a Chinese Han population.
AB  - Although human leukocyte antigen (HLA)-G gene polymorphism is low, it may
      influence levels of protein expression and, in some cases, has been associated
      with pregnancy diseases. Apart from the 23 HLA-G alleles, including a null allele
      known as HLA-G*0105N, a 14-bp deletion or insertion in the 3'UT region also
      contributes to the HLA-G gene polymorphism. In order to discover any correlation
      between the 14-bp deletion polymorphism and pregnancy diseases, we isolated the
      genomic DNA from 24 recurrent spontaneous abortions (RSA) patients and 88 normal
      fertile control individuals using the salted out method. Exon-8 of HLA-G gene of
      the two groups was amplified by polymerase chain reaction, respectively, and
      analyzed by electrophoresis on 9% nondenaturing polyacrylamide gel and stained
      with ethidium bromide. Differences between the two groups were compared using the
      chi(2) test. The results were there was no significant difference in allelic
      frequencies of 14-bp deletion polymorphism between normal control and RSA
      patients; frequency of -14 bp/+14 bp heterozygotes was significantly increased in
      RSA patients as compared with normal fertile controls. Our results are similar to
      a study of Indian women but contradictory to a study of Danish women. This
      discrepancy may be due to ethnic differences.

PMID- 17445193
TI  - HLA-G polymorphism and evolution.
AB  - Six proteins, one null allele and 22 human leukocyte antigen (HLA)-G alleles were
      found in humans. Bonobo, chimpanzee and gorilla only show one allele and
      orangutan shows five alleles. All Cercopithecus alleles show stop codons at
      position 164 (Macaca mulatta with seven DNA alleles, Macaca fascicularis with
      seven DNA alleles and Cercopithecus aethiops with three DNA alleles). Cotton-top
      tamarin New World monkeys showed 20 DNA and protein alleles; the major
      histocompatibility complex (MHC)-G New World sequences seem to be closer to MHC-E
      and lack typical MHC-G primates intron 2-specific deletion. This seems to suggest
      that MHC-G genes in New World primates are not orthologous and that their
      function may be similar to that of classical presenting MHC genes.

PMID- 17445194
TI  - 14th International HLA and Immunogenetics Workshop: report on understanding
      antibodies in transplantation.
AB  - A session of the 14 International Histocompatibility Workshop brought together
      experts representing the major clinical protocols, clinical research, and basic
      research dealing with overcoming the barrier of alloantibody in transplantation
      and in understanding the mechanisms by which those antibodies exert their effect
      on a transplanted organ. This report is an integration of the presentations of
      those scientists.

PMID- 17445195
TI  - 14th International HLA and Immunogenetics Workshop: report on the Prospective
      Chronic Rejection Project.
AB  - An international collaborative study of 45 transplant centers was undertaken at
      the 14th International HLA (human leukocyte antigen) and Immunogenetics Workshop
      to see if HLA antibodies detected posttransplant are predictive of chronic graft
      failure. With the newly developed assay, MICA (major histocompatibility complex
      class I-related chain A) antibodies were also measured and their effect analyzed.
      Total of 5219 sera from patients who were more than 6 months posttransplant with
      functioning graft were tested for HLA antibodies by enzyme-linked immunosorbent
      assay, flow cytometry, or Luminex. HLA antibodies were found in 27.2% of kidney
      patients, 23.6% in the liver, 52.7% in the heart, and 21.7% in the lung. The
      method of antibody testing did not have a marked influence on the frequency of
      antibodies detected. MICA antibodies were detected in 15% of kidney patients, 30%
      of heart patients, and 31% of liver patients. Among 948 kidney patients who had
      HLA antibodies, 7.3% had rejected their graft within 1 year of testing, compared
      with 1.7% in 2615 patients without HLA antibodies (P= 0.8 x 10(-17)). Death
      occurred in 1.4% of total kidney patients and did not correlate to the presence
      of antibodies. We conclude that patients with posttransplant HLA antibodies
      indeed have a higher rate of chronic graft failure and that posttransplant
      antibodies are predictive of chronic rejection.

PMID- 17445196
TI  - 14th International HLA and Immunogenetics Workshop: report on the structural
      basis of HLA compatibility.
AB  - Under auspices of the 14th International Human Leukocyte Antigen (HLA) and
      Immunogenetics Workshop, multilaboratory collaborative studies were organized
      addressing the following projects: (1) identification of structurally defined
      class I and class II HLA epitopes by human monoclonal antibodies, (2) assessment
      of the relative immunogenicity of structurally defined donor HLA mismatches in
      kidney transplantation, and (3) evaluation of the usefulness of structurally
      based HLA matching in platelet transfusion support of alloimmunized
      thrombocytopenic patients. This progress report describes a preliminary
      HLAMatchmaker-based data analysis in each project. The findings support the
      clinical usefulness of structural HLA matching.

PMID- 17445197
TI  - 14th International HLA and Immunogenetics Workshop: report of progress in
      methodology, data collection, and analyses.
AB  - The Biostatistics Component of the 13th International Histocompatibility Workshop
      (IHWS) developed the PyPop (Python for Population Genomics) software framework
      for high-throughput analysis and quality control (QC) assessments of highly
      polymorphic genotype data. Since its initial release, the software has had
      several new analysis modules added to it. These additions, combined with improved
      data filtering and QC modules, facilitate analyses of data at different levels
      (allele, haplotype, amino acid sequence, and nucleotide sequence). Since the 13th
      IHWS, much of the human leukocyte antigen (HLA) data from the workshop, QCed via
      PyPop and other methods, have been made publicly available through the Major
      Histocompatibility Complex database web site at the National Center for
      Biotechnology Information (http://ncbi.nih.gov/mhc/). The Anthropology/Human
      Genetic Diversity component (AHGDC) data have been used in a variety of studies.
      Prugnolle et al. used this data to corroborate a model of pathogen-driven
      selection as a factor related to high levels of diversity at HLA loci. Using a
      comparative genomics approach contrasting results for HLA and non-HLA markers,
      Meyer et al. analyzed a subset of the 13th IHWS AHGDC data and showed that HLA
      loci show detectable signs of both natural selection and the demographic history
      of populations.

PMID- 17445198
TI  - Population samples and genotyping technology.
AB  - The 14th International HLA (human leukocyte antigen) Immunogenetics Workshop
      (14th-IHIWS) Biostatistics and Anthropology/Human Genetic Diversity project
      continues the population sampling, genotype data generation, and biostatistic
      analyses of the 13th International Histocompatibility Workshop Anthropology/Human
      Genetic Diversity Component, with the overall goal of further characterizing
      global HLA allele and haplotype diversity and better describing the relationships
      between major histocompatibility complex diversity, geography, linguistics, and
      population history. Since the 13th Workshop, new investigators have and continue
      to be recruited to the project and new high-resolution class I and class II
      genotype data are being generated for 112 population samples from around the
      world.

PMID- 17445199
TI  - PyPop update--a software pipeline for large-scale multilocus population genomics.
AB  - Population genetic statistics from multilocus genotype data inform our
      understanding of the patterns of genetic variation and their implications for
      evolutionary studies, generally, and human disease studies in particular. In any
      given population one can estimate haplotype frequencies, identify deviation from
      Hardy-Weinberg equilibrium, test for balancing or directional selection, and
      investigate patterns of linkage disequilibrium. Existing software packages are
      oriented primarily toward the computation of such statistics on a population-by
      population basis, not on comparisons among populations and across different
      statistics. We developed PyPop (Python for Population Genomics) to facilitate the
      analyses of population genetic statistics across populations and the
      relationships among different statistics within and across populations. PyPop is
      an open-source framework for performing large-scale population genetic analyses
      on multilocus genotype data. It computes the statistics described above, among
      others. PyPop deploys a standard Extensible Markup Language (XML) output format
      and can integrate the results of multiple analyses on various populations that
      were performed at different times into a common output format that can be read
      into a spreadsheet. The XML output format allows PyPop to be embedded as part of
      a larger analysis pipeline. Originally developed to analyze the highly
      polymorphic genetic data of the human leukocyte antigen region of the human
      genome, PyPop has applicability to any kind of multilocus genetic data. It is the
      primary analysis platform for analyzing data collected for the Anthropological
      component of the 13th and 14th International Histocompatibility Workshops. PyPop
      has also been successfully used in studies by our group, with collaborators, and
      in publications by several independent research teams.

PMID- 17445200
TI  - An apportionment of human HLA diversity.
AB  - In this study, we estimate the amount of human leukocyte antigen (HLA) genetic
      diversity in the global human population at three levels of population hierarchy:
      within populations; among populations within continents and among continents on
      large sets of HLA population data gathered during the last international
      histocompatibility and immunogenetics workshops and conferences. The results
      indicate that loci HLA-A, B, C, DRB1, DQA1 and DQB1 exhibit a higher amount of
      diversity among individuals of the same population than observed for neutral
      polymorphisms (average diversity of 90.3% compared with 84.4%-87.6% for neutral
      DNA markers). On the other hand, the value (84%) obtained for HLA-DPB1 is very
      similar to those observed for non-HLA nuclear markers, in agreement with other
      results suggesting the neutrality of this locus. In addition to the results of
      the hierarchical analysis of variance, selective neutrality tests indicate that
      loci B, C and DRB1 are the most affected by balancing selection. However, one
      cannot discriminate between a direct selective effect acting on those loci or a
      general effect of associative overdominance acting over the large HLA region (in
      linkage disequilibrium) encompassing those loci.

PMID- 17445201
TI  - Tools for analysing ambiguous HLA data.
AB  - Analyses of large projects involving human leukocyte antigen data often face the
      difficulty of having data sets gathered using distinct techniques and resolution
      levels. Furthermore, it is not infrequent that missing and ambiguous data arise
      at one or several loci. This article describes a set of computer programs that
      can be used to work efficiently with these kinds of data. The tasks of concern
      include format conversions, data recoding and replacement, and Expectation
      Maximization (gene-counting) based frequency estimation for sets with ambiguous
      cases either under the assumption of Hardy-Weinberg equilibrium frequencies or
      when some deviation exists (measured by a one degree of freedom inbreeding
      coefficient). This set of utilities is built on the top of a data format formally
      defined. The formal definition of the format allows to express all kinds of
      observable ambiguities, to define a simpler form for writing and manipulating
      data set files and to make substantial modifications of the actual symbols chosen
      to describe the data.

PMID- 17445202
TI  - 14th International HLA and Immunogenetics Workshop: report on mapping
      microsatellite markers in the major histocompatibility complex region.
AB  - This paper describes the use of the program e-pcr to localize 687 known major
      histocompatability complex (MHC) microsatellite primer pairs to their sequence
      positions in several genomic assemblies across the MHC region. The sequences used
      were the Sequences of Sanger Institute's MHC Haplotype Project: COX, PGF, QBL, as
      well as the Celera, and Reference (PGF across extended MHC) sequences from the
      NCBI genomic build 36. More than 95% (664/687) of the markers mapped
      unambiguously to the Reference assembly sequence. All primer pairs used in this
      analysis, and those were previously unknown to UniSTS, have now been assigned
      permanent public UniSTS identifiers. Mapping and descriptive data for each primer
      pair are available at the publicly accessible dbMHC microsatellite resource:
      http://www.ncbi.nlm.nih.gov/projects/mhc/xslcgi.fcgi?cmd=mssearch.

PMID- 17445203
TI  - Nomenclature for HLA microsatellites.
AB  - A proposal for a standardized nomenclature for human leukocyte antigen (HLA)
      microsatellites is presented. It provides recommendations for Microsatellites as
      regards to locus name, primer names, and denominations for alleles.

PMID- 17445204
TI  - 14th International HLA and Immunogenetics Workshop: report on the HLA component
      of type 1 diabetes.
AB  - The type 1 diabetes (T1D) component of the 13th International Histocompatibility
      Workshop (IHW) obtained microsatellite (msat) and human leukocyte antigen (HLA)
      DR/DQ data on case/control and family samples through an international
      collaboration. The aim was to detect the effects of susceptibility loci on the
      HLA complex independent of the primary determinants in the class II region (HLA
      DR/DQ). As part of the activity of the 14th International HLA and Immunogenetics
      Workshop (14th IHIWS), a T1D workshop was held to present analyses of the 13th
      IHW data and to discuss the current status of knowledge about the genetics of
      T1D. These data are now available online through dbMHC, a web-based resource
      established by the National Center for Biotechnology. Continuing work since the
      13th IHW has resulted in published work showing heterogeneity of DR3 haplotypes
      in data sets from the 13th IHW and Human Biological Data Interchange (HBDI). In
      addition, we identified markers that define DRB1*1501 DQB1*0602 haplotypes
      conferring reduced protection from diabetes in a Swedish 13th IHW data set.
      Further analyses of the 13th IHW data set not only showed some significant
      results but also demonstrated extensive heterogeneity reminiscent of non-HLA
      genes. The haplotype analysis in HBDI families identified two msats with
      significant effects on susceptibility and statistically significant age of onset
      effects at class III markers that are not because of linkage disequilibrium, with
      class I alleles known to affect age of onset. The above studies underscore the
      importance of refining our understanding of susceptibility associated with genes
      in the HLA complex.

PMID- 17445205
TI  - 14th International HLA and Immunogenetics Workshop: report on joint study on MHC
      and infection.
AB  - The 'MHC and Infection' study of the 14th International HLA and Immunogenetics
      Workshop was undertaken to evaluate the contribution of specific variants of
      major histocompatibility complex (MHC) and non-MHC genes that are specifically
      associated with higher probabilities of infection, disease severity, and
      progression in different populations.

PMID- 17445206
TI  - Immunogenetics of mycobacterial infections in the North Indian population.
AB  - Several lines of evidence highlight the genetic basis of risk to develop
      mycobacterial diseases. Human leukocyte antigen (HLA)-DR2 alleles (DRB1*1501 and
      DRB1*1502) have been found to be strongly associated with mycobacterial disease,
      especially the more severe forms such as lepromatous leprosy and multidrug
      resistant pulmonary tuberculosis. In this study, DNA-based high-resolution typing
      techniques of polymerase chain reaction-sequence-specific oligonucleotide probe
      were used to determine the distribution of HLA-DR/DQ alleles in patients with
      leprosy and pulmonary tuberculosis. Analysis of different DR2 subtypes based on
      valine/glycine dimorphism at codon beta86 in pocket 1 of HLA-DR showed an inverse
      relationship of DR2 alleles with V/G as the severity of disease increased both in
      leprosy and in pulmonary tuberculosis.

PMID- 17445207
TI  - Mycobacterial infections: PARK2 and PACRG associations in leprosy.
AB  - An overview of investigations indicating an important role of host genetics, both
      major histocompatibility complex (MHC) and non-MHC, in leprosy.

PMID- 17445208
TI  - Association of variants in the IL12B gene with leprosy and tuberculosis.
AB  - There is a great range in outcomes after mycobacterial infections, and this is
      probably due to individual variation in immune responses. One of the key cytokine
      regulators of the immune response is interleukin (IL-) 12. The IL12B gene encodes
      the p40 chain of both IL-12 and IL-23 and it has two major variant sites at which
      different alleles are associated with increased levels of gene expression and
      with susceptibility to a range of immune-related diseases. We hypothesized that
      IL12B variants associated with increased expression would be as associated with
      susceptibility to persistent mycobacterial infection. We tested this hypothesis
      by genotyping Indian subjects, having either leprosy or tuberculosis (TB), as
      well as ethnically matched controls. Subjects with leprosy were less likely to
      have the 3'UTR genotype associated with lower IL12B expression (P= 0.001).
      Subjects with TB were not only more likely to have the high-expressing IL12B
      promoter genotype (P= 0.01) but also more likely to have this in the same
      haplotype with the high expressing 3'UTR allele (P= 0.0009). These results
      suggest these infectious diseases may be improved by modulating IL-l2p40
      production.

PMID- 17445209
TI  - Influence of inhibitory killer immunoglobulin-like receptors and their HLA-C
      ligands on resolving hepatitis C virus infection.
AB  - An estimated 2%-3% of the world's population is chronically infected with
      hepatitis C virus (HCV) and this is a major cause of liver disease worldwide.
      Following acute infection, outcome is variable with acute HCV successfully
      resolved in some individuals (20%-30%), but in the majority of cases the virus is
      able to persist. Co-infection with human immunodeficiency virus has been
      associated with a negative impact on the course of HCV infection. The host's
      immune response is an important correlate of HCV infection outcome and disease
      progression. Natural killer (NK) cells provide a major component of the antiviral
      immune response by recognising and killing virally infected cells. NK cells
      modulate their activity through a combination of inhibitory and activatory
      receptors such as the killer immunoglobulin-like receptors (KIRs) that bind to
      human leukocyte antigen (HLA) Class I molecules. In this workshop component, we
      addressed the influence of KIR genotypes and their HLA ligands on resolving HCV
      infection and we discuss the implications of the results of the study of Lopez
      Vazquez et al. on KIR and HCV disease progression.

PMID- 17445210
TI  - Association of killer immunoglobulin-like receptors and their HLA Class I ligands
      with progression of chronic hepatitis C virus infection.
AB  - This part of the workshop addressed the results of a study on killer
      immonoglobulin-like receptors and hepatitis C virus disease progression.

PMID- 17445211
TI  - 14th IHIWS MHC and Infection Study: summary and conclusions.
AB  - International collaborative efforts through histocompatibility workshops have
      helped greatly in collating useful data on interpopulation differences in genetic
      susceptibility to mycobacterial and viral infections. These are imperative in
      exploring the genetic basis of disease pathogenesis and host resistance. Because
      infectious diseases involve multigenic complex traits, several genetic variants
      contribute modifying effects on the disease but disease outcome depends on the
      net relative hazards of individual genetic loci taken together. Further because
      occurrence of genetic variants varies in a population-specific manner, it becomes
      even more complicated to show genetic influences across populations. For this,
      large study cohorts representing different ethnicities are needed. Information
      thus gained could lead to the development of more effective vaccine design to
      combat or diminish the emergence of pathogenic multidrug resistant forms.

PMID- 17445212
TI  - 14th International HLA and Immunogenetics Workshop: report on HLA expression and
      cancer.

PMID- 17445213
TI  - HLA expression and cancer--14th IHIWS immunohistochemistry quality control
      exercise exchange results.
AB  - An immunohistochemistry (IH) quality control exercise was conducted as part of
      the 14th International HLA (human leukocyte antigen) and Immunogenetics Workshop
      (IHIWS) HLA Expression and Cancer component. Six laboratories participated and
      the exercises involved performing IH using three monoclonal antibodies (HC-10,
      beta2m and SI00) on three sequential paraffin-embedded melanoma sections provided
      by one laboratory. High-resolution digital photographs of five IH-stained
      sections were also distributed for interpretation. While there was generally good
      agreement between laboratories, several differences in staining and
      interpretation of IH sections were identified and possible reasons given.
      Interpretation of the high-resolution digital photographs showed a high level of
      concordance between laboratories. It is suggested that further exercises are
      conducted as part of future collaborative activities in order to further
      characterise areas of variability between IH performance and interpretation of
      results.

PMID- 17445214
TI  - Fourier transform infrared imaging as a method for detection of HLA class I
      expression in melanoma without the use of antibody.
AB  - Human leukocyte antigen (HLA) class I expression in melanoma is usually assessed
      using immunohistochemical staining. Here we report on the use of Fourier
      transform infrared (FTIR) hyperspectral imaging, a method widely used in two
      dimensional analysis of chemical components, to study HLA class I expression in
      tissue. Two-dimensional cluster colour images derived from unsupervised
      hierarchical cluster analysis of FTIR hyperspectral data on melanoma sections
      were compared with consecutive sections that were immunohistochemically stained
      for class I expression. HLA-class-I-positive and -negative areas were
      differentiated by FTIR cluster images in all eight melanoma sections investigated
      without the need for antibody attachment. FTIR imaging enables the distinction of
      HLA-class-I-positive from class-I-negative areas in melanoma. This method is
      accurate, rapid and cost-effective.

PMID- 17445215
TI  - Different mechanisms can lead to the same altered HLA class I phenotype in
      tumors.
AB  - Human leukocyte antigen (HLA) class I plays an important role in tumor
      recognition and rejection. Total or selective losses of HLA class I antigens
      (classified into seven HLA class I altered phenotypes) represent one of the main
      routes of tumor escape from immune surveillance. Abnormal expression of HLA class
      I has been reported in different human tumor samples with distinct underlying
      mechanisms. Notably, different molecular mechanisms can generate the same altered
      HLA class I phenotype. Here, we describe various molecular mechanisms that can
      lead to HLA total loss or downregulation (phenotype I) in melanoma, colorectal
      carcinoma and bladder cancer.

PMID- 17445216
TI  - Analysis of HLA class I alterations in tumors: choosing a strategy based on known
      patterns of underlying molecular mechanisms.
AB  - The application of peptide-based immunotherapy in the treatment of cancer has
      known limitations in patients with loss or downregulation of human leukocyte
      antigen (HLA) class I expression on tumor cells. These alterations diminish the
      ability of cancer cells to present tumor peptides to T cells and therefore lead
      to failure of peptide-based cancer vaccination. Abnormal expression of HLA class
      I molecules in malignant cells is a frequent event that ranges from total loss of
      class I molecules to partial loss of HLA-specific haplotypes or alleles.
      Different mechanisms underlie these alterations and might require different
      therapeutic approaches. A complete characterization of molecular defects may
      suggest strategies for the selection and follow-up of patients undergoing T-cell
      based immunotherapy. Moreover, a precise identification of the mechanism leading
      to HLA class I defects in patients with cancer will help develop new,
      personalized patient-tailored treatment protocols. Here, we describe several
      examples showing the necessity and feasibility of making detailed individual
      analysis of HLA alteration mechanisms based on previously described molecular
      patterns in different types of malignancy. We recommend using this approach, at
      least in some patients, to enhance the therapeutic benefit of cancer
      immunotherapy.

PMID- 17445217
TI  - 14th International HLA and Immunogenetics Workshop: report on joint study on
      canine DLA diversity.
AB  - The canine DLA diversity component of the 14th International HLA and
      Immunogenetics (IHI) Workshop had three main aims: i) to establish the range of
      DLA class II (DRBI, DQA1, DQB1) diversity and their distribution in dog breeds,
      ii) to identify DLA class II haplotypes by segregation in families and iii) to
      examine DLA class II associations with disease susceptibility. Over 1600 dogs
      from seven participating laboratories were typed for three DLA class II loci as
      part of the workshop. Standard sequence-based typing methods were used, and all
      the data were of high quality.

PMID- 17445218
TI  - Canine DLA diversity: 1. New alleles and haplotypes.
AB  - The aim of this component was to establish the range of DLA diversity in as many
      dog breeds as possible. In particular, we wanted to collect breeds that had not
      previously been studied. Data were submitted of 937 dogs of over 80 different
      breeds, and these included 17 'new' breeds. Twenty-eight new alleles were
      identified including 21 DLA-DRB1, 2 DLA-DQA1 and 5 DLA-DQB1 alleles. These
      occurred in many new haplotype combinations. One haplotype was identified that
      appeared to lack DQB1. Two other haplotypes carry two DQB1 genes. It was clear
      that each dog breed has a restricted range of DLA alleles and haplotypes, and no
      breed had all 88 haplotypes identified in this study.

PMID- 17445219
TI  - Canine DLA diversity: 2. Family studies.
AB  - The canine Major Histocompatibility Complex is referred to as DLA (for dog
      leukocyte antigen). There are no published studies on DLA segregation in the dog,
      so this part of the DLA workshop aimed to collect DNA from multigeneration
      families of different breeds of dogs. Twenty-two families of dogs were submitted
      to the workshop, comprising 313 individuals, of which 247 had one or both parents
      available.

PMID- 17445220
TI  - Canine DLA diversity: 3. Disease studies.
AB  - There are many millions of dogs worldwide, and these dogs have many different
      functions. The most obvious use is providing companionship, but there are also
      many working dogs, including guide dogs for the blind, hearing dogs, guard dogs
      and farm dogs, to mention a few. The health and welfare of these dogs is of great
      concern to dog owners, dog breeders and to those who use dogs in their work. Dogs
      spontaneously develop many diseases that are very similar to their human
      counterparts. Dogs may, therefore, provide exceptional animal models for such
      diseases. Identifying genetic markers in the dog may be easier than in humans,
      and may then provide useful information about genes that can be transferred to
      humans. This study looked for associations between DLA and two autoimmune
      diseases of the dog, diabetes and hypothyroidism. DLA associations were found for
      both of these diseases.

PMID- 17445221
TI  - 14th International HLA and Immunogenetics Workshop: report from the reproductive
      immunology component.
AB  - The aim of the study was to investigate whether human leukocyte antigen (HLA)
      allele sharing between partners or the maternal killer immunoglobulin-like
      receptor (KIR) repertoire is associated with recurrent spontaneous abortion (RSA)
      and repeated implantation failure after in vitro fertilization (IVF)/embryo
      transfer. From a total population of 158 RSA couples, 40 couples with repeated
      implantation failures (IVF) and 81 control couples, reported by five different
      laboratories, analysis was performed for (a) HLA sharing in 50 RSA, 31 IVF and 31
      control couples, (b) DQA1*0505 sharing/homozygosity among partners in 108 RSA, 40
      IVF and 36 control couples, and (c) the women's KIR repertoire in 46 RSA, 26 IVF
      and 36 control wives. RSA couples were divided into alloimmune aborter (RSAallo)
      and autoimmune aborter (RSAauto). The results oppose to the suggestion that
      increased HLA sharing per se or a limited maternal KIR repertoire predisposes to
      RSA or IVF failure. However, the observation of a slightly higher percentage of
      DQA1*0505 sharing in the RSAauto and the IVF group needs further investigation.
      The ratio of inhibitory to activating KIR (actKIR) was slightly lower in RSAallo
      and IVF women (1.9 vs 2.6 in controls), while in a high percentage of these
      women, the standard receptors of the KIR A haplotype were combined with actKIR/s
      of the haplotype B (66.6% and 45.4% vs 20% and 15.3% in RSAauto and control
      groups). This may suggest a possible involvement of actKIRs in embryo
      implantation and the maintenance of pregnancy and also requires further
      investigation.

PMID- 17445222
TI  - 14th International HLA and Immunogenetics Workshop: report on the immunogenetics
      of aging.
AB  - The 'Immunogenetics of Aging' is a newly included component within the 14th
      International HLA and Immunogenetics Workshop. The aim of this component was to
      determine the contribution of human leukocyte antigen (HLA), cytokine genes and
      other major histocompatibility complex-encoded loci to successful aging and to
      determine an increased capacity to reach the extreme limits of life span. Two
      main data sets from four European populations were included in this study:
      unrelated healthy elderly individuals and ethnically matched young controls, and
      families with longevity members. Analysis was focused on HLA class I and II and
      cytokine gene polymorphisms. Preliminary results showed increased frequencies of
      DRB1*11- and DRB*16-associated haplotypes that were found to be protective for
      autoimmune diseases in some populations. Additionally, in families with longevity
      members, alleles and haplotypes positively associated with autoimmunity were not
      observed. Analysis of cytokine gene polymorphisms showed prevalence of anti
      inflammatory profiles in healthy elderly individuals. Inheritance of extended
      haplotypes in families with longevity members allowed the identification of
      immunogenetic profiles that could be predictive for longevity. These preliminary
      studies indicate the relevance of genes regulating immune functions in human
      longevity and the importance of clarifying further their impact in successful
      aging.

PMID- 17445223
TI  - Optical glutamate sensor for spatiotemporal analysis of synaptic transmission.
AB  - Imaging neurotransmission is expected to greatly improve our understanding of the
      mechanisms and regulations of synaptic transmission. Aiming at imaging glutamate,
      a major excitatory neurotransmitter in the CNS, we developed a novel optical
      glutamate probe, which consists of a ligand-binding domain of alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor glutamate receptor
      GluR2 subunit and a small molecule fluorescent dye. We expected that such
      fluorescent conjugates might report the microenvironmental changes upon protein
      conformational changes elicited by glutamate binding. After more than 100
      conjugates were tested, we finally obtained a conjugate named E (glutamate)
      optical sensor (EOS), which showed maximally 37% change in fluorescence intensity
      upon binding of glutamate with a dissociation constant of 148 nm. By immobilizing
      EOS on the cell surface of hippocampal neuronal culture preparations, we pursued
      in situ spatial mapping of synaptically released glutamate following presynaptic
      firing. Results showed that a single firing was sufficient to obtain high
      resolution images of glutamate release, indicating the remarkable sensitivity of
      this technique. Furthermore, we monitored the time course of changes in
      presynaptic activity induced by phorbol ester and found heterogeneity in
      presynaptic modulation. These results indicate that EOS can be generally
      applicable to evaluation of presynaptic modulation and plasticity. This EOS-based
      glutamate imaging method is useful to address numerous fundamental issues about
      glutamatergic neurotransmission in the CNS.

PMID- 17445224
TI  - Deficit of NMDA receptor activation in CA1 hippocampal area of aged rats is
      rescued by D-cycloserine.
AB  - Activation of the glycine modulatory site of the N-methyl-D-aspartate glutamate
      receptor (NMDAR) may reduce cognitive impairments associated with normal ageing.
      In order to test this hypothesis, we assessed the effects of the partial agonist
      D-cycloserine (DCS) on cellular activities involved in memory formation. This was
      performed in CA1 cellular networks of adult and aged Sprague-Dawley rat
      hippocampal slices using extracellular field excitatory postsynaptic potential
      recordings. Synaptic potentials specifically mediated by NMDAR were significantly
      reduced in aged animals. DCS increased the magnitude of these responses in both
      adult and old rats but this effect was significantly higher in the latter, thus
      reversing the age-related decrease in NMDAR synaptic potentials. NMDAR-mediated
      theta burst long-term potentiation (TBS-LTP) as well as long-term depression
      (LTD) of synaptic transmission, prominent models for the cellular basis of
      learning and memory, were also weakened in aged animals. Age-related alterations
      of both forms of synaptic plasticity were rescued by DCS. In addition, the DCS
      induced decrease in basal fast glutamatergic neurotransmission involving the
      activation of inhibitory glycinergic receptors, previously reported in young rats
      (Rouaud & Billard, 2003), was severely attenuated in aged animals. In summary,
      our results indicate that the facilitation of NMDAR activation through its
      glycine-binding site rescues the age-related deficit of cellular mechanisms of
      learning and memory. Such physiological evidences suggest that this modulation
      site of NMDAR represents an important target to alleviate cognitive deficits
      associated with normal ageing.

PMID- 17445225
TI  - The neuroprotective effects of the WldS gene are correlated with proteasome
      expression rather than apoptosis.
AB  - The Wld(s) gene (slow Wallerian degeneration) specifically delays axonal
      degeneration following injury and in several models of neurodegenerative
      diseases. It thus provides an interesting tool to study mechanisms of
      neurodegeneration. We previously crossed the Wld(s) mice with a mouse mutant that
      has a motoneuron disease (pmn for progressive motor neuronopathy) and showed that
      the Wld(s) gene prevented axonal loss, increased the life-span and prolonged the
      survival of the motoneuron cell bodies. In this study we show that spinal
      motoneurons of pmn/pmn mice, as opposed to axons, die by apoptosis that cannot be
      prevented by the Wld(s) gene. However, this same gene could partially rescue the
      proteasome impairment observed in motoneuron cell bodies and axons of pmn/pmn
      mice. We conclude that the neuroprotective effect of the Wld(s) gene is not
      related to an inhibition of apoptosis but could possibly be linked to a
      regulation in proteasome expression.

PMID- 17445226
TI  - Brain-derived neurotrophic factor prevents the nigrostriatal degeneration induced
      by human immunodeficiency virus-1 glycoprotein 120 in vivo.
AB  - Glycoprotein 120 (gp120) from the T-tropic strain of the human immunodeficiency
      virus type 1 has been shown to cause neuronal apoptosis through activation of the
      chemokine receptor CXCR4. Therefore, reducing CXCR4 expression may prevent gp120
      mediated apoptosis. Brain-derived neurotrophic factor (BDNF) is known to reduce
      both gp120 neurotoxicity and CXCR4 expression in vitro. The scope of this work is
      to establish whether BDNF is neuroprotective against gp120 in vivo and, if so,
      whether this effect correlates with its ability to down-regulate CXCR4. Serotype
      2 adeno-associated viral vector encoding for BDNF (rAAV-BDNF) or control vector
      was microinjected into the striata of adult rats. Two weeks later gp120 was
      injected into the same striatum, and apoptosis determined. Pretreatment with rAAV
      BDNF prior to gp120 microinjection prevented caspase-3 activation as well as in
      situ terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling in the
      striatum and substantia nigra. In addition, rAAV-BDNF reversed the loss of
      tyrosine hydroxylase immunoreactivity induced by gp120 in both areas. CXCR4
      expression was then determined by immunohistochemistry and RT-PCR, and found to
      be decreased in striata of rAAV-BDNF-treated rats. Conversely, BDNF heterozygous
      mice exhibited an increase in CXCR4 mRNA levels compared to wild-type
      littermates. Our data suggest that down-regulation of CXCR4 expression may
      contribute to the neuroprotective activity of BDNF against gp120 toxicity in the
      basal ganglia.

PMID- 17445227
TI  - cAMP mediates ammonia-induced programmed cell death in the microglial cell line
      BV-2.
AB  - Although ammonia is a well-known neuropathogenic factor, the cellular mechanisms
      of ammonia toxicity are less characterized. Up to now, the main focus of ammonia
      toxicity has been on astrocytes and neurons. Despite the significance of
      microglia in neurodegenerative diseases, little is known about their
      responsiveness to ammonia. In the present study, we found that ammonia triggered
      mitosis at concentrations between 30 microm and 3.0 mm but apoptosis at
      concentrations >or= 1.0 mm in the murine microglial cell line BV-2. Most
      apoptotic cells showed an accumulation of condensed chromatin at the nuclear
      envelope, blebbing of the plasma membrane, formation of apoptotic bodies and an
      increase in caspase 3/7 activity. Blockade of caspase 3/7 activity by Ac-DEVD-CHO
      suppressed ammonia-induced apoptosis. Surprisingly, some BV-2 cells exposed to
      ammonia displayed clear signs of mitotic catastrophe, a type of cell death
      occurring during mitosis. In a further series of experiments, we found that
      cyclic adenosine 3',5'-monophosphate (cAMP) mediated the apoptogenic effects of
      ammonia, because (i) ammonia dose-dependently elevated the intracellular cAMP
      level, (ii) blockade of the adenylyl cyclase by SQ-22536 suppressed ammonia
      induced apoptosis, (iii) inhibition of phosphodiesterases (PDEs) by the
      nonselective PDE inhibitor IBMX, or by the PDE4-selective inhibitor rolipram,
      increased the relative number of apoptotic cells, and (iv) the cAMP analogues 8
      bromoadenosine cAMP and Sp-cAMP mimicked the effect of ammonia and triggered
      apoptosis. Taken together, our results indicate that distinct concentrations of
      ammonia trigger opposite signalling pathways in microglial cells.

PMID- 17445228
TI  - Paradoxical opsin expressing cells in the inner retina that are augmented
      following retinal degeneration.
AB  - Here we reveal a population of cells that express cone photoreceptor opsins that
      are located in the inner retina, distant from outer retinal photoreceptors. These
      cells are present in rodents and human. They also express a range of key proteins
      critical in the cone phototransduction cascade and make contact with other
      retinal neurons. Their opsins are not generally confined to cellular specialized
      regions but are present throughout the plasma membrane, although their nuclear
      configurations are similar to those of outer retinal cones. This population is
      distinct from the ganglion cells that contain melanopsin and which are known to
      be inner retinal irradiance detectors regulating circadian behaviour.
      Surprisingly, the size of the population of short wavelength opsin positive cells
      in the ganglion cell layer is plastic. In normal animals their number declines
      with age. However, their numbers increase significantly in response to outer
      retinal photoreceptor loss, probably by drawing on a pool of inner retinal cells
      that express cone specific markers, but not opsins.

PMID- 17445229
TI  - Transplantation of conditionally immortal auditory neuroblasts to the auditory
      nerve.
AB  - Cell transplantation is a realistic potential therapy for replacement of auditory
      sensory neurons and could benefit patients with cochlear implants or acoustic
      neuropathies. The procedure involves many experimental variables, including the
      nature and conditioning of donor cells, surgical technique and degree of
      degeneration in the host tissue. It is essential to control these variables in
      order to develop cell transplantation techniques effectively. We have
      characterized a conditionally immortal, mouse cell line suitable for
      transplantation to the auditory nerve. Structural and physiological markers
      defined the cells as early auditory neuroblasts that lacked neuronal, voltage
      gated sodium or calcium currents and had an undifferentiated morphology. When
      transplanted into the auditory nerves of rats in vivo, the cells migrated
      peripherally and centrally and aggregated to form coherent, ectopic 'ganglia'.
      After 7 days they expressed beta 3-tubulin and adopted a similar morphology to
      native spiral ganglion neurons. They also developed bipolar projections aligned
      with the host nerves. There was no evidence for uncontrolled proliferation in
      vivo and cells survived for at least 63 days. If cells were transplanted with the
      appropriate surgical technique then the auditory brainstem responses were
      preserved. We have shown that immortal cell lines can potentially be used in the
      mammalian ear, that it is possible to differentiate significant numbers of cells
      within the auditory nerve tract and that surgery and cell injection can be
      achieved with no damage to the cochlea and with minimal degradation of the
      auditory brainstem response.

PMID- 17445230
TI  - Emergence of topography in the developing hamster retinocollicular projection:
      axial differences and the role of cell death.
AB  - The precise ordering of the hamster retinocollicular projection is established
      over the first two postnatal weeks, coincident with developmental cell death. We
      have used quantitative retrograde labelling to define topographic precision in
      the early postnatal projection, to describe its refinement and to assess the
      contribution played by selective retinal ganglion cell death. The hamster's short
      gestation period allows the investigation of events occurring prenatally in other
      rodents. Discrete injections of fluorescent beads in the superior colliculus
      followed by isodensity contour analysis of labelled retinal cells reveals a
      dramatic decrease in the extent of retina labelled between postnatal days 2, 6
      and 12 (P2, P6, P12): the 20% contour encloses 38.3%, 8.3% and 1.8% of the retina
      at these ages. Paired injections of two different tracers at variable
      rostrocaudal (R-C) separations at P2 produced complete overlap of label even when
      injections were separated by over 1 mm. This was not true for paired mediolateral
      injections at P2 that were separated by more than 500 microm. Analysis of the
      segregation of the two tracers ('nearest-neighbour analysis') shows topography
      improving with age so that by P12 injections separated rostrocaudally by more
      than 500 microm produced no overlap in the retina. To examine the contribution of
      selective ganglion cell death to topographic refinement, animals given paired R-C
      injections at P2 were allowed to survive until P12. Nearest-neighbour analysis
      reveals significantly more order in the P2-P12 retinae than after overnight
      survival. Thus, selective cell death plays a small but appreciable role in
      correction of topographical errors.

PMID- 17445231
TI  - The innervation of parvalbumin-containing interneurons by VIP-immunopositive
      interneurons in the primary somatosensory cortex of the adult rat.
AB  - gamma-Aminobutyric acid (GABA)ergic interneurons of neocortex consist of many
      subgroups with extremely heterogeneous morphological, physiological and molecular
      properties. To explore the putative effect of the vasoactive intestinal
      polypeptide-immunopositive (VIP +) neurons on neocortical circuitry, the number
      and distribution of VIP + boutons were analysed on somatodendritic domains of 272
      parvalbumin immunopositive (PV +) 3D-reconstructed neurons. The synaptic nature
      of 91% of somatic and 76% of dendritic contacts was verified by electron
      microscopy. The target PV + neurons were separated in two significantly different
      groups by means of cluster analysis. The first group (Cluster 1, 26%) received on
      average five times more VIP + synapses than those of the second group. The second
      group (Cluster 2, 74%) contained cells that were poorly innervated by VIP +
      boutons or did not have either somatic or dendritic or any VIP innervation at
      all. The cells of Cluster 1 had a soma size and total dendritic length
      significantly smaller than that of Cluster 2, however, they received three times
      more dendritic synapses, which resulted in a five times higher VIP + synaptic
      density on dendrites. Our results showed that although most of the PV + cells are
      innervated by VIP + boutons at a varying degree, some 6% of PV + cells received
      no input from VIP + interneurons. This suggests a refined morphological basis to
      influence the majority of the PV + interneurons, which are very effectively
      controlling pyramidal cell firing. Together with metabolic and neuromodulatory
      effects of VIP, this would probably result in an enhanced responsiveness of the
      latter cell type to tactile stimuli.

PMID- 17445232
TI  - Glycogen synthase kinase 3 activation is essential for the snake phospholipase A2
      neurotoxin-induced secretion in chromaffin cells.
AB  - Neuroendocrine chromaffin cells were used to study the mechanism of the snake
      phospholipase A2 (PLA2) neurotoxin enhancement of exocytosis. Notexin, beta
      bungarotoxin, taipoxin or textilotoxin enhanced the fast release of
      catecholamines elicited by flash photolysis of cytosolic caged calcium. Such an
      increase correlates with the capacity of these neurotoxins to cause fragmentation
      of the F-actin cortical barrier with subsequent accumulation of vesicles in the
      proximity of the plasma membrane. These PLA2 neurotoxins do not act via protein
      kinase C activation, which is known to promote F-actin fragmentation. Lithium,
      RO31-8220 and SB216763, three inhibitors of the glycogen synthase kinase 3,
      prevent both the alteration of the F-actin peripheral cortex and the enhancement
      of fast release elicited by these neurotoxins. In addition, glycogen synthase
      kinase 3 has been detected by immunolocalization in a membranous compartment of
      the chromaffin cell endoplasmic reticulum (ER). These results suggest that the
      activation of this enzyme plays a major role in the enhancement of exocytosis of
      the readily releasable granules caused by PLA2 neurotoxins in neuroendocrine
      chromaffin cells.

PMID- 17445233
TI  - Disruption of Kir6.2-containing ATP-sensitive potassium channels impairs
      maintenance of hypoxic gasping in mice.
AB  - Hypoxic gasping emerges under severe hypoxia/ischemia in various species,
      exerting a life-protective role by assuring minimum ventilation even in loss of
      consciousness. However, the molecular basis of its generation and maintenance is
      not well understood. Here we found that mice lacking Kir6.2- but not Kir6.1
      containing ATP-sensitive potassium (K(ATP)) channels [knockout (KO) mice]
      exhibited few gaSPS when subjected to abrupt ischemia by decapitation, whereas
      wild-type mice all exhibited more than 10 gaSPS. Under anesthesia, wild-type mice
      initially responded to severe hypoxic insult with augmented breathing (tachypnea)
      accompanied by sighs and subsequent depression of respiratory frequency. Gasping
      then emerged and persisted stably (persistent gasping); if the hypoxia continued,
      several gaSPS with distinct patterns appeared (terminal gasping) before cessation
      of breathing. KO mice showed similar hypoxic responses but both depression and
      the two types of gasping were of much shorter duration than in wild-type mice.
      Moreover, in the unanesthetized condition, the onset of terminal gasping in KO
      mice, which was always earlier than in wild-type mice, was unaltered by
      decreasing O(2) concentrations within the severe range (4.5-7.0%), whereas onset
      in wild-type mice became earlier in response to lowered O(2) concentrations.
      Thus, the mechanism responsible for regulating the hypoxic response in accordance
      with the severity of the hypoxia was dysfunctional in these KO mice, suggesting
      that Kir6.2-containing K(ATP) channels are critically involved in the maintenance
      rather than the generation of hypoxic gasping and depression of respiratory
      frequency.

PMID- 17445234
TI  - Candidate pheromone receptors provide the basis for the response of distinct
      antennal neurons to pheromonal compounds.
AB  - Males of the moth species Heliothis virescens are able to detect the female
      released pheromone with remarkable sensitivity and specificity, distinguishing
      between highly related pheromonal compounds. In the past, electrophysiological
      studies succeeded in assigning sensory hairs to identified compounds revealing
      three functional types of long sensilla trichodea housing neurons specifically
      responding to distinct semiochemicals. The specific responsiveness implies that
      the sensory neurons express different receptor types tuned to pheromone
      components. In this study we demonstrate that heterologously expressed candidate
      pheromone receptors from Heliothis responded to several pheromonal compounds,
      including the major sex-pheromone component Z-11-hexadecenal indicating a limited
      specificity of each receptor type. Nonetheless, based on functional analysis and
      in situ hybridization studies the analysed receptor types could tentatively be
      assigned to types of long sensilla trichodea, containing the pheromone-binding
      proteins (PBPs) HvirPBP1 and HvirPBP2 in the sensillum lymph. Substituting
      organic solvent with PBPs to solubilize the hydrophobic pheromone compounds in
      functional assays revealed an increase in sensitivity and especially specificity.
      It was found that in the presence of HvirPBP2, cells expressing the receptor type
      HR13 specifically responded to the main component of the sex pheromone blend
      only. The data provide further evidence that a combination of a distinct receptor
      type and binding protein underlie the specific response observed in the detection
      of a pheromone component in vivo.

PMID- 17445235
TI  - Topographic distribution of output neurons in cerebellar nuclei and cortex to
      somatotopic map of primary motor cortex.
AB  - To investigate the somatotopic organization of the cerebellum, we analysed
      multisynaptic inputs to the primary motor cortex (MI) using retrograde
      transneuronal transport of rabies virus. At 3 days after rabies injections into
      proximal forelimb, distal forelimb and hindlimb representations of the macaque
      MI, second-order neurons via the thalamus were labeled in the deep cerebellar
      nuclei, including the dentate (DN), anterior interpositus (AIN) and posterior
      interpositus nuclei. In the DN, the labeling of both the forelimb and hindlimb
      was seen mainly in the dorsal aspect. The labeling of the hindlimb was located
      rostral to that of the forelimb and the labeling of the proximal forelimb was
      located slightly rostral to that of the distal forelimb. The same rostrocaudal
      arrangement was observed in the AIN. In the posterior interpositus nucleus,
      however, labeling from the MI hindlimb and forelimb representations largely
      overlapped. At the 4-day postinjection period, third-order labeling occurred in
      Purkinje cells of the cerebellar hemisphere. The Purkinje cell labeling from the
      forelimb representation, including the proximal and distal regions, was observed
      primarily in lobules IV-VI and crus I. The proximal forelimb labeling was both
      rostral and lateral to that of the distal forelimb within lobules IV-VI. However,
      the hindlimb labeling was seen both rostral and lateral to that of the proximal
      forelimb within lobules III-VI. These results indicate that the hindlimb,
      proximal forelimb and distal forelimb are arranged rostrocaudally in the DN and
      AIN, whereas there is dual somatotopy along the rostrocaudal and lateromedial
      axes in the cerebellar cortex.

PMID- 17445236
TI  - Heterogeneity in the coding in rat barrel cortex of the velocity of protraction
      of the macrovibrissae.
AB  - Rats whisk to explore their environment and obtain information on object
      features, and the responses of somatosensory cortical neurones must precisely
      encode aspects of whisker movements. Using trapezoidal stimuli to deflect
      whiskers, with a wide range of velocities and amplitudes of whisker protraction,
      we recorded responses from a relatively homogeneous population of isolated cells
      and neuronal multiunits within the postero-medial barrel sub-field of
      somatosensory cortex, and analysed responses in an early post-stimulus-onset
      window. For 92% of neurones the function relating response strength to velocity
      was a saturating sigmoid but there were differences between neurones in the
      slopes and ranges over which responses changed. Responses of other neurones were
      non-monotonic, with response strength decaying at very high whisker deflection
      velocities. Generally, barrel cortex neurones were responsive to a much wider
      range of whisker protraction velocities than hitherto reported, especially to
      much slower velocities than generally assumed to be the main range of
      sensitivity. This carries implications for coding of whisker deflection velocity,
      a parameter that appears to be a significant information-bearing element of
      natural whisking. The effect of amplitude of deflection upon neural responses was
      evident in only approximately 24% of units and only when the dominant velocity
      effect had saturated.

PMID- 17445237
TI  - Lateral hypothalamic 'command neurons' with axonal projections to regions
      involved in both feeding and thermogenesis.
AB  - The concept of 'command neurons', whereby single neurons mediate complex and
      complementary motor functions to generate a stereotyped behaviour, is well
      developed in invertebrate physiology. The term has also been adopted more
      recently to explain the neural basis of 'fight or flight'. In this study we have
      investigated the possibility that single lateral hypothalamic neurons have the
      necessary neuroanatomical connections to coordinate two complementary limbs of
      body weight control, feeding and thermogenesis, thereby acting as 'command
      neurons'. The transynaptic retrograde transport of pseudorabies virus (Bartha)
      from a thermogenic endpoint in the brown adipose tissue of rats has been used in
      conjunction with other neuronal tracers, introduced into putative CNS feeding
      centres, to assess the potential for the involvement of command neurons in
      coordinating these processes. In discrete regions of the lateral hypothalamus,
      neurons have been identified which have the necessary complement of orexigenic
      peptides and collateral branching axons to both putative feeding sites and
      thermogenic sites in brown fat to qualify as candidate central command neurons
      controlling body weight.

PMID- 17445238
TI  - Constant light housing during nursing causes human DSPS (delayed sleep phase
      syndrome) behaviour in Clock-mutant mice.
AB  - Delayed sleep phase syndrome (DSPS) is very often seen among patients with sleep
      wake rhythm disorders. Humans with the 3111C allele of the human Clock gene tend
      to demonstrate a higher evening preference on the morningness-eveningness (ME)
      preference test. DSPS is thought to be an extreme form of this evening
      preference. Clock-mutant mice have been proposed as an animal model of evening
      preference. In this study, we looked at whether constant light (LL) housing of
      Clock-mutant mice during lactation would result in evening preference and/or
      DSPS. Housed under light-dark (LD) or constant dark (DD) conditions during the
      lactation period, both wild-type and Clock-mutant mice did not show a phase-delay
      in the locomotor activity measured under light-dark conditions, whereas constant
      light housing during lactation significantly caused a delayed onset. The
      magnitude of the delay during the light-dark cycle was positively associated with
      free-running period measured during constant darkness. Among wild, heterozygote,
      and homozygote pups born from heterozygous dams, only homozygote pups showed a
      delayed onset. Constant light-housed Clock-mutant mice exhibited a lower number
      and delayed peak of phospho-MAPK-immunoreactive cells in core regions of the
      suprachiasmatic nucleus (SCN) compared to light-dark housed wild-type or Clock
      mutant mice. Activity onset returned to normal with daily melatonin injection at
      the lights-off time for 5 days. The present results demonstrate that Clock-mutant
      mice exposed to constant light during lactation can function as an animal model
      of DSPS and can be used to gain an understanding of the ethological aspects of
      DSPS as well as to find medication for its treatment.

PMID- 17445239
TI  - Locomotor exercise alters expression of pro-brain-derived neurotrophic factor,
      brain-derived neurotrophic factor and its receptor TrkB in the spinal cord of
      adult rats.
AB  - Previous evidence indicates that locomotor exercise is a powerful means of
      increasing brain-derived neurotrophic factor (BDNF) and its signal transduction
      receptor TrkB mRNA levels, immunolabeling intensity and number of BDNF- and TrkB
      immunopositive cells in the spinal cord of adult rats but the contribution of
      specific cell types to changes resulting from long-term activity is unknown. As
      changes in BDNF protein distribution due to systemic stimuli may reflect either
      its in-situ synthesis or its translocation from other sources, we investigated
      where BDNF and TrkB mRNA are expressed in the spinal lumbar segments. We report
      on the cell types defined by size, BDNF mRNA levels and number of cells with TrkB
      transcripts in sedentary and exercised animals following 28 days of treadmill
      walking. In the majority of cells, exercise increased perikaryonal levels of BDNF
      mRNA but did not affect TrkB transcript levels. Bidirectional changes in a number
      of TrkB mRNA-expressing cells occurred in small groups of ventral horn neurons.
      An increase in BDNF transcripts was translated into changes in pro-BDNF and BDNF
      levels. A 7-day walking regimen increased BDNF protein levels similarly to 28-day
      treadmill walking. Our observations indicate that long- and short-term locomotor
      activity of moderate intensity produce stimuli sufficient to recruit a majority
      of spinal cells to increased BDNF synthesis, suggesting that continuous tuning of
      pro-BDNF and BDNF levels permits spinal networks to undergo trophic modulation
      not requiring changes in TrkB mRNA supply.

PMID- 17445240
TI  - Correlated species differences in the effects of cannabinoid ligands on anxiety
      and on GABAergic and glutamatergic synaptic transmission.
AB  - Cannabinoid ligands show therapeutic potential in a variety of disorders
      including anxiety. However, the anxiety-related effects of cannabinoids remain
      controversial as agonists show opposite effects in mice and rats. Here we
      compared the effects of the cannabinoid agonist WIN-55,212 and the CB1 antagonist
      AM-251 in CD1 mice and Wistar rats. Special attention was paid to antagonist
      agonist interactions, which had not yet been studied in rats. In mice, WIN-55,212
      decreased whereas AM-251 increased anxiety. The antagonist abolished the effects
      of the agonist. In contrast, WIN-55,212 increased anxiety in rats. Surprisingly,
      the antagonist potentiated this effect. Cannabinoids affect both GABAergic and
      glutamatergic functions, which play opposite roles in anxiety. We hypothesized
      that discrepant findings resulted from species differences in the relative
      responsiveness of the two transmitter systems to cannabinoids. We investigated
      this hypothesis by studying the effects of WIN-55,212 on evoked hippocampal
      inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs). IPSCs were one
      order of magnitude more sensitive to WIN-55,212 in mice than in rats. In mice,
      IPSCs were more sensitive than EPSCs to WIN-55,212. This is the first study
      showing that the relative cannabinoid sensitivity of GABA and glutamate
      neurotransmission is species-dependent. Based on behavioural and
      electrophysiological findings, we hypothesize that WIN-55,212 reduced anxiety in
      mice by affecting GABA neurotransmission whereas it increased anxiety in rats via
      glutamatergic mechanisms. In rats, AM-251 potentiated this anxiogenic effect by
      inhibiting the anxiolytic GABAergic mechanism. We suggest that the anxiety
      related effects of cannabinoids depend on the relative cannabinoid responsiveness
      of GABAergic and glutamatergic neurotransmission.

PMID- 17445241
TI  - Neurokinin 3 receptor activation potentiates the psychomotor and nucleus
      accumbens dopamine response to cocaine, but not its place conditioning effects.
AB  - Neurokinin(3) receptors (NK(3)-Rs) have been implicated in psychomotor activity
      and reinforcement mechanisms. Recently, we showed that NK(3)-R antagonism blocked
      the psychostimulant properties of cocaine both in rats and in primates. Here,
      using in vivo microdialysis in the nucleus accumbens (NAc) of freely moving rats,
      we investigated the effect of the NK(3)-R agonist senktide (0.2 and 0.4 mg/kg
      s.c.) on the cocaine-evoked increase in dopamine. Cocaine (10 mg/kg i.p.)
      increased dopamine levels to 404 and 480% of baseline in the core and shell of
      the NAc, respectively. Pretreatment with senktide at a dose of 0.2 mg/kg
      potentiated this effect to 666 (core) and 869% (shell) of baseline, without
      having any effect on dopamine when given alone. Behavioural measurements revealed
      that 0.2 mg/kg senktide also potentiated the cocaine-induced increase in
      horizontal and vertical activity. Senktide alone induced a short-lasting increase
      in activity that was not accompanied by any alterations of the neurochemical
      parameters. In conditioned place preference (CPP) experiments, senktide
      pretreatment did not alter CPP induced by cocaine (5 and 10 mg/kg i.p.), and had
      no effect when given alone. Likewise, cocaine-conditioned locomotor activity was
      not affected by the NK(3)-R agonist. However, as in the microdialysis studies,
      cocaine-induced (5 and 10 mg/kg i.p.) hyperactivity was potentiated by senktide,
      and there was evidence for a facilitation of sensitization to the hyperlocomotor
      effects of cocaine by senktide. These data provide evidence that NK(3)-Rs are
      involved in the control of the hyperlocomotor and NAc DA response to cocaine, but
      not in cocaine-induced CPP.

PMID- 17445242
TI  - Prenatal choline availability modulates hippocampal neurogenesis and neurogenic
      responses to enriching experiences in adult female rats.
AB  - Increased dietary intake of choline early in life improves performance of adult
      rats on memory tasks and prevents their age-related memory decline. Because
      neurogenesis in the adult hippocampus also declines with age, we investigated
      whether prenatal choline availability affects hippocampal neurogenesis in adult
      Sprague-Dawley rats and modifies their neurogenic response to environmental
      stimulation. On embryonic days (ED) 12-17, pregnant rats ate a choline
      supplemented (SUP-5 g/kg), choline sufficient (SFF-1.1 g/kg), or choline-free
      (DEF) semisynthetic diet. Adult offspring either remained in standard housing or
      were given 21 daily visits to explore a maze. On the last ten exploration days,
      all rats received daily injections of 5-bromo-2-deoxyuridine (BrdU, 100 mg/kg).
      The number of BrdU+ cells was significantly greater in the dentate gyrus in SUP
      rats compared to SFF or DEF rats. While maze experience increased the number of
      BrdU+ cells in SFF rats to the level seen in the SUP rats, this enriching
      experience did not alter cell proliferation in DEF rats. Similar patterns of cell
      proliferation were obtained with immunohistochemical staining for neuronal marker
      doublecortin, confirming that diet and exploration affected hippocampal
      neurogenesis. Moreover, hippocampal levels of the brain-derived neurotrophic
      factor (BDNF) were increased in SUP rats as compared to SFF and DEF animals. We
      conclude that prenatal choline intake has enduring effects on adult hippocampal
      neurogenesis, possibly via up-regulation of BDNF levels, and suggest that these
      alterations of neurogenesis may contribute to the mechanism of life-long changes
      in cognitive function governed by the availability of choline during gestation.

PMID- 17445243
TI  - Hippocampal activity, but not plasticity, is required for early consolidation of
      fear conditioning with a short trace interval.
AB  - The dorsal hippocampus is required for explicit cue fear conditioning only when a
      temporal gap is inserted between conditioned stimulus (CS) termination and
      unconditioned stimulus (US) onset (trace fear conditioning). To examine the role
      of the dorsal hippocampus in associating temporally discontiguous stimuli and to
      minimize the potential contribution of contextual cues, fear conditioning was
      conducted using a relatively short (3-s) trace interval. Inactivation of the
      dorsal hippocampus using the AMPA receptor antagonist NBQX (3 microg/hemisphere)
      or the GABA(A) agonist muscimol (5 microg/hemisphere) disrupted trace fear
      conditioning when conducted immediately following training. Trace conditioning
      was not disrupted significantly when NBQX was infused either before or 2 h after
      training. Similarly, NBQX infusions were not effective when the CS and US
      overlapped (delay conditioning). Moreover, trace conditioning was not impaired by
      intrahippocampal infusion of either the NMDA receptor antagonist AP5 (5
      microg/hemisphere) or the L-type voltage-gated calcium channel (VGCC) blocker
      diltiazem (20 or 40 microg/hemisphere). These data suggest that the involvement
      of the dorsal hippocampus in short trace interval fear conditioning is largely
      restricted to the early period of memory consolidation, during which time it
      mediates the storage of long-term memory in other brain regions.

PMID- 17445244
TI  - The influence of Pavlovian cues on instrumental performance is mediated by CaMKII
      activity in the striatum.
AB  - Pavlovian cues associated with reward exert a powerful motivational influence on
      the performance of goal-directed actions. This motivational process depends
      critically on the ventral striatum, although little is known about the cellular
      and molecular mechanisms that mediate it. In the current experiments we examined
      the role of calcium calmodulin-dependent kinase II (CaMKII) by using transgenic
      mice that express a constitutively active form of this kinase. We found that
      controlled expression of active CaMKII in the striatum did not affect learning
      but did impair the motivation of goal-directed actions by Pavlovian cues
      associated with reward. Mutant mice learned to lever press for reward, remained
      sensitive to outcome devaluation and contingency degradation manipulations, and
      were able to acquire Pavlovian responses to cues paired with reward. However,
      Pavlovian cues were completely unable to motivate lever pressing in mutant mice.
      This was true even in mice trained with the CaMKII transgene turned off and then
      tested with it turned on. We were also able to suppress transgene expression in
      impaired mutants and fully restore the motivational effects of reward cues in
      these animals. Therefore, the current experiments demonstrate that normal CaMKII
      activity in the striatum is essential for the motivational effects of reward cues
      on goal-directed actions.

PMID- 17445245
TI  - Lesions of rat infralimbic cortex enhance renewal of extinguished appetitive
      Pavlovian responding.
AB  - It is well established that extinction is highly context dependent, and several
      behavioural phenomena associated with the expression of extinction (spontaneous
      recovery, reinstatement and renewal) have been described as resulting from this
      context dependency. It has previously been shown that lesions of the infralimbic
      (IL) region of the medial prefrontal cortex result in increased levels of
      spontaneous recovery and reinstatement of an extinguished appetitive Pavlovian
      conditioned response. The current study shows that lesions of the IL cortex also
      result in increased renewal of a conditioned response when tested in the
      acquisition context. Thirteen IL-lesioned and 14 sham-lesioned rats were trained
      on an appetitive Pavlovian task in one context (Context A) followed by extinction
      in a different context (Context B); animals were then tested for renewal of
      responding in both Context A and B. Both groups demonstrated similarly low levels
      of responding when tested in the extinction context (B), and greater responding
      (i.e. renewal) when tested in the acquisition context (A). Further, the level of
      response renewal was greater in IL-lesioned animals. The results are discussed in
      relation to the possible role of the IL cortex in contextual control of
      extinction.

PMID- 17445246
TI  - Neonatal functional blockade of the entorhinal cortex results in disruption of
      accumbal dopaminergic responses observed in latent inhibition paradigm in adult
      rats.
AB  - Latent inhibition (LI) has been found to be disrupted in non-treated patients
      with schizophrenia. Dopaminergic (DAergic) dysfunctioning is generally
      acknowledged to occur in schizophrenia. Various abnormalities in the entorhinal
      cortex (ENT) have been described in patients with schizophrenia. Numerous data
      also suggest that schizophrenia has a neurodevelopmental origin. The present
      study was designed to test the hypothesis that reversible inactivation of the ENT
      during neonatal development results in disrupted DA responses characteristic of
      LI in adult rats. Tetrodotoxin (TTX) was microinjected locally in the left ENT at
      postnatal day 8 (PND8). DA variations were recorded in the dorsomedial shell and
      core parts of the nucleus accumbens (Nacc) using in vivo voltammetry in freely
      moving grown-up rats in a LI paradigm. In the first session the animals were pre
      exposed (PE) to the conditional stimulus (banana odour) alone. In the second they
      were aversively conditioned to banana odour. In the third (test) session the
      following results were obtained in PE animals subjected to temporary inactivation
      of the ENT at PND8: (1) aversive behaviour was observed in TTX-PE conditioned
      animals; (2) DA variations in the dorsomedial shell and core parts of the Nacc
      were similar in TTX-PE and non-pre-exposed conditioned rats. These findings
      strongly suggest that neonatal disconnection of the ENT disrupts LI in adult
      animals. They may further our understanding of the pathophysiology of
      schizophrenia.

PMID- 17445247
TI  - Neurotoxic lesions of ventrolateral prefrontal cortex impair object-in-place
      scene memory.
AB  - Disconnection of the frontal lobe from the inferotemporal cortex produces
      deficits in a number of cognitive tasks that require the application of memory
      dependent rules to visual stimuli. The specific regions of frontal cortex that
      interact with the temporal lobe in performance of these tasks remain undefined.
      One capacity that is impaired by frontal-temporal disconnection is rapid learning
      of new object-in-place scene problems, in which visual discriminations between
      two small typographic characters are learned in the context of different visually
      complex scenes. In the present study, we examined whether neurotoxic lesions of
      ventrolateral prefrontal cortex in one hemisphere, combined with ablation of
      inferior temporal cortex in the contralateral hemisphere, would impair learning
      of new object-in-place scene problems. Male macaque monkeys learned 10 or 20 new
      object-in-place problems in each daily test session. Unilateral neurotoxic
      lesions of ventrolateral prefrontal cortex produced by multiple injections of a
      mixture of ibotenate and N-methyl-D-aspartate did not affect performance.
      However, when disconnection from inferotemporal cortex was completed by ablating
      this region contralateral to the neurotoxic prefrontal lesion, new learning was
      substantially impaired. Sham disconnection (injecting saline instead of
      neurotoxin contralateral to the inferotemporal lesion) did not affect
      performance. These findings support two conclusions: first, that the
      ventrolateral prefrontal cortex is a critical area within the frontal lobe for
      scene memory; and second, the effects of ablations of prefrontal cortex can be
      confidently attributed to the loss of cell bodies within the prefrontal cortex
      rather than to interruption of fibres of passage through the lesioned area.

PMID- 17445248
TI  - Domain-related differentiation of working memory in the Japanese macaque (Macaca
      fuscata) frontal cortex: a positron emission tomography study.
AB  - The lateral prefrontal cortex (LPFC) is important for working memory (WM) task
      performance. Neuropsychological and neurophysiological studies in monkeys suggest
      that the lateral prefrontal cortex is functionally segregated based on the
      working memory domain (spatial vs. non-spatial). However, this is not supported
      by most human neuroimaging studies, and the discrepancy might be due to
      differences in methods and/or species (monkey neuropsychology/physiology vs.
      human neuroimaging). We used positron emission topography to examine the
      functional segregation of the lateral prefrontal cortex of Japanese macaques
      (Macaca fuscata) that showed near 100% accuracy on spatial and non-spatial
      working memory tasks. Compared with activity during the non-working memory
      control tasks, the dorsolateral prefrontal cortex (DLPFC) was more active during
      the non-spatial, but not during the spatial, working memory task, although a
      muscimol microinjection into the dorsolateral prefrontal cortex significantly
      impaired the performance of both working memory tasks. A direct comparison of the
      brain activity between the two working memory tasks revealed no differences
      within the lateral prefrontal cortex, whereas the premotor area was more active
      during the spatial working memory task. Comparing the delay-specific activity,
      which did not include task-associated stimulus/response-related activity,
      revealed more spatial working memory-related activity in the posterior parietal
      and premotor areas, and more non-spatial working memory-related activity in the
      dorsolateral prefrontal cortex and hippocampus. These results suggest that
      working memory in the monkey brain is segregated based on domain, not within the
      lateral prefrontal cortex but rather between the posterior parietal-premotor
      areas and the dorsolateral prefrontal-hippocampus areas.

PMID- 17445249
TI  - Sensitivity to direction and orientation of random dot stereobars in the monkey
      visual cortex.
AB  - We are able to judge the direction of movement and orientation of objects because
      they have contrast-defined edges. However, we are also able to perceive the
      orientation and direction of movement of stereobars made of random dot
      stereograms in the absence of contrast-defined edges. We recorded 207 disparity
      sensitive cells from visual areas V1 and V2 of two Macaca mulatta monkeys while
      performing an attentive fixation task. Luminance defined bars and random-dot
      stereo-defined bars were used to assess direction and orientation selectivity of
      these cells. Orientation and direction preference for luminance bars and for
      stereobars showed a statistically significant relationship (r=0.83, P<0.01 for
      direction; r=0.63, P<0.01 for orientation). However, disparity-sensitive cells
      from these areas seem to be more sensitive to luminance than to stereobars
      regarding orientation and direction of movement. Similar results were obtained
      when the two areas were considered separately. Our results show that cells in
      areas V1 and V2 of the monkey visual cortex are able to detect the orientation
      and direction of movement of stereobars in a manner similar to those of luminance
      defined bars. This finding is relevant because to detect the direction and
      orientation of stereobars a comparison between left and right eye inputs is
      required.

PMID- 17445250
TI  - Modulation of neuronal responses in macaque primary visual cortex in a memory
      task.
AB  - The primary visual cortex, a relatively early station in the visual pathway, has
      long been considered mainly as a site of basic feature detection but evidence is
      emerging that is consistent with the existence of feedback influences from higher
      cortical areas. We show that in a delayed match-to-sample memory task, where the
      monkey needs to remember both the visual pattern and its location, there is
      significant modulation of neuronal activity in the primary visual cortex
      suggestive of a feedback signal. Responses to identical patterns are remarkably
      different depending upon their place in the memory task. These modulatory
      influences are significantly less when the same visual patterns are shown during
      a simple fixation task, where these stimuli can be ignored and not attended to.
      The results indicate that neural processing specific to attentional and mnemonic
      functions can involve even primary sensory areas.

PMID- 17445251
TI  - Illusory shape representation in the monkey inferior temporal cortex.
AB  - Perceived boundaries without physical differences between shape and background
      are called illusory contours (ICs). ICs and real contours (RCs) activate the
      early processing stages of the macaque visual pathway and the occipitotemporal
      areas of the human visual system in a similar way. However, it is not known how
      these contours are processed further in the highest visual areas. We tested how
      the responses of inferior temporal cortical (IT) neurons of macaque monkeys
      change in relationship to figures with RCs or ICs. The same set of figures
      [coloured pictures, ICs and silhouettes (SILs)] was presented to awake, fixating
      rhesus monkeys while the single-cell activity was recorded in the anterior part
      of the IT. Most of the neurons responsive to RCs were also responsive to the same
      shapes presented as ICs. The average net firing rates, however, were
      significantly lower for the illusory stimuli than for the stimuli in the RC
      conditions, and the latency of the responses was significantly longer for the ICs
      than for the RCs. The shape selectivity was found to be different for coloured
      stimuli and ICs, and similar for SILs and ICs, suggesting the invariance of
      selectivity to shapes having the same contour but lacking internal surface
      information. These results suggest different modes of processing of RCs and ICs
      in the IT, which might explain the differences in their perception.

PMID- 17445252
TI  - Behavioral and neuroanatomical correlates of white matter asymmetries in
      chimpanzees (Pan troglodytes).
AB  - Although behavioral and brain asymmetries have been documented in non-human
      primates, lateralization in cortical connectivity as reflected in white matter
      has not been described in any species, despite the intrinsic theoretical interest
      in white matter expansion during primate brain evolution. Here we report evidence
      of population-level leftward asymmetries in the white matter of chimpanzees. We
      further report that lateralization in white matter correlates with their
      handedness as well as neuroanatomical asymmetries in the precentral gyrus. These
      findings suggest that chimpanzees show asymmetries in cortical connectivity and
      these may serve as the foundation for morphological and behavioral laterality in
      primates, including humans.

PMID- 17445253
TI  - The role of cingulate cortex in the detection of errors with and without
      awareness: a high-density electrical mapping study.
AB  - Error-processing research has demonstrated that the brain uses a specialized
      neural network to detect errors during task performance but the brain regions
      necessary for conscious awareness of an error are poorly understood. In the
      present study we show that two well-known error-related event-related potential
      (ERP) components, the error-related negativity (ERN) and error positivity (Pe)
      have a differential relationship with awareness during performance of a manual
      response inhibition task optimized to examine error awareness. While the ERN was
      unaffected by the participants' conscious experience of errors, the Pe was only
      seen when participants were aware of committing an error. Source localization of
      these components indicated that the ERN was generated by a caudal region of the
      anterior cingulate cortex (ACC) while the Pe was associated with contributions
      from a more anterior ACC region and the posterior cingulate-precuneus. Tonic EEG
      measures of cortical arousal were correlated with individual rates of error
      awareness and showed a specific relationship with the amplitude of the Pe. The
      latter finding is consistent with evidence that the Pe represents a P3-like
      facilitation of information processing modulated by subcortical arousal systems.
      Our data suggest that the ACC might participate in both preconscious and
      conscious error detection and that cortical arousal provides a necessary setting
      condition for error awareness. These findings may be particularly important in
      the context of clinical studies in which a proper understanding of self
      monitoring deficits requires an explicit measurement of error awareness.

PMID- 17445254
TI  - DNA vaccine constructs against enterovirus 71 elicit immune response in mice.
AB  - BACKGROUND: Enterovirus 71 (EV71) is a major causative viral agent responsible
      for large outbreaks of hand, foot and mouth disease (HFMD), a common rash illness
      in children and infants. There is no effective antiviral treatment for severe
      EV71 infections and no vaccine is available. The objectives of this study were to
      design and construct a DNA vaccine against Enterovirus 71 using the viral capsid
      protein (VP1) gene of EV71 and to verify the functionality of the DNA vaccine in
      vitro and in vivo. METHODS: The VP1 gene of EV71 from two local outbreak isolates
      were amplified using PCR and then inserted into a eukaryotic expression vector,
      pVAX1. The 3.9 kb recombinant constructs were transformed into competent E. coli
      cells and the positive clones were screened and selected using PCR analysis,
      restriction digestion analysis and DNA sequencing. The constructs were then
      tested for protein expression in Vero cells. Subsequently, in the in vivo
      studies, female Balb/c mice were immunized with the DNA vaccine constructs.
      Enzyme Linked Immunosorbent Assay (ELISA) and virus neutralizing assay were
      performed to detect the presence of anti-VP1 IgG in mice and its neutralizing
      effect against the EV71. RESULTS: The pVAX1 vector was successfully cloned with
      the VP1 gene from each of the isolate (S2/86/1 and 410/4) in the correct
      orientation and in-frame. The DNA vaccine constructs with the VP1 gene were shown
      to be expressed in a cell-free in vitro expression system. The VP1 protein was
      successfully expressed in the mammalian cell line and was detected using RT-PCR,
      Indirect Immunofluorescence Assay (IFA) and western blotting. The anti-VP1 IgG
      levels in mice immunized with the DNA vaccine constructs increased after the
      first booster but declined following the second booster. The anti-VP1 IgG in the
      mice immunized with the DNA vaccine constructs exhibited neutralising activity
      against EV71. CONCLUSION: The promising results obtained in the present study
      have prompted further testing to improve the expression and immunogenicity of
      this potential EV71 DNA vaccine.

PMID- 17445255
TI  - Micro-epidemiology of Plasmodium falciparum malaria: Is there any difference in
      transmission risk between neighbouring villages?
AB  - BACKGROUND: Malaria control strategies are designed as a solution for either the
      whole region or the whole country and are assumed to suit every setting. There is
      a need to shift from this assumption because transmission may be different from
      one local setting to another. The aim of this study was to assess the risk of
      clinical malaria given the village of residence among under-five children in
      rural north-western Burkina Faso. METHODS: 867 children (6-59 months) were
      randomly selected from four sites. Interviewers visited the children weekly at
      home over a one-year period and tested them for fever. Children with fever were
      tested for malaria parasites. An episode of clinical malaria was defined as fever
      (axillary temperature > or = 37.5 degrees C) + parasites density > or = 5,000
      parasites/microl. Logistic regression was used to assess the risk of clinical
      malaria among children at a given site of residence. RESULTS: Children
      accumulated 758 person years (PYs). Overall, 597 episodes of clinical malaria
      were observed, giving an incidence rate of 0.79 per PY. The risk of clinical
      malaria varied amongst the four sites. Taking one village as reference the odds
      ratio for the other three sites ranged from 0.66; 95% CI: 0.44-0.98 to 1.49; 95%
      CI: 1.10-2.01. CONCLUSION: Malaria control strategies should be designed to fit
      the local context. The heterogeneity of transmission should be assessed at the
      district level to allow cost-effective resource allocation that gives priority to
      locations with high risk. Functional routine health information systems could
      provide the necessary data for context specific risk assessment.

PMID- 17445256
TI  - Homology modeling of major intrinsic proteins in rice, maize and Arabidopsis:
      comparative analysis of transmembrane helix association and aromatic/arginine
      selectivity filters.
AB  - BACKGROUND: The major intrinsic proteins (MIPs) facilitate the transport of water
      and neutral solutes across the lipid bilayers. Plant MIPs are believed to be
      important in cell division and expansion and in water transport properties in
      response to environmental conditions. More than 30 MIP sequences have been
      identified in Arabidopsis thaliana, maize and rice. Plasma membrane intrinsic
      proteins (PIPs), tonoplast intrinsic proteins (TIPs), Nod26-like intrinsic
      protein (NIPs) and small and basic intrinsic proteins (SIPs) are subfamilies of
      plant MIPs. Despite sequence diversity, all the experimentally determined
      structures belonging to the MIP superfamily have the same "hour-glass" fold.
      RESULTS: We have structurally characterized 39 rice and 31 maize MIPs and
      compared them with that of Arabidopsis. Homology models of 105 MIPs from all
      three plant species were built. Structure-based sequence alignments were
      generated and the residues in the helix-helix interfaces were analyzed. Small
      residues (Gly/Ala/Ser/Thr) are found to be highly conserved as a group in the
      helix-helix interface of MIP structures. Individual families sometimes prefer one
      or another of the residues from this group. The narrow aromatic/arginine (ar/R)
      selectivity filter in MIPs has been shown to provide an important constriction
      for solute permeability. Ar/R regions were analyzed and compared between the
      three plant species. Seventeen TIP, NIP and SIP members from rice and maize have
      ar/R signatures that are not found in Arabidopsis. A subgroup of rice and maize
      NIPs has small residues in three of the four positions in the ar/R tetrad,
      resulting in a wider constriction. These MIP members could transport larger
      solute molecules. CONCLUSION: Small residues are group-conserved in the helix
      helix interface of MIP structures and they seem to be important for close helix
      helix interactions. Such conservation might help to preserve the hour-glass fold
      in MIP structures. Analysis and comparison of ar/R selectivity filters suggest
      that rice and maize MIPs could transport more diverse solutes than Arabidopsis
      MIPs. Thus the MIP members show conservation in helix-helix interfaces and
      diversity in aromatic/arginine selectivity filters. The former is related to
      structural stability and the later can be linked to functional diversity.

PMID- 17445257
TI  - Aerobic exercise in adolescents with obesity: preliminary evaluation of a modular
      training program and the modified shuttle test.
AB  - BACKGROUND: Increasing activity levels in adolescents with obesity requires the
      development of exercise programs that are both attractive to adolescents and
      easily reproducible. The aim of this study was to develop a modular aerobic
      training program for adolescents with severe obesity, with a focus on variety,
      individual targets and acquiring physical skills. We report here the effects on
      aerobic fitness from a pilot study. Furthermore, we examined the feasibility of
      the modified shuttle test (MST) as an outcome parameter for aerobic fitness in
      adolescents with severe obesity. METHODS: Fifteen adolescents from an inpatient
      body weight management program participated in the aerobic training study (age
      14.7 +/- 2.1 yrs, body mass index 37.4 +/- 3.5). The subjects trained three days
      per week for 12 weeks, with each session lasting 30-60 minutes. The modular
      training program consisted of indoor, outdoor and swimming activities.
      Feasibility of the MST was studied by assessing construct validity, test-retest
      reliability and sensitivity to change. RESULTS: Comparing pretraining and end of
      training period showed large clinically relevant and significant improvements for
      all aerobic indices: e.g. VO2 peak 17.5%, effect size (ES) 2.4; Wmax 8%, ES 0.8.
      In addition, a significant improvement was found for the efficiency of the
      cardiovascular system as assessed by the oxygen pulse (15.8%, ES 1.6). Construct
      validity, test-retest reliability and sensitivity to change of the MST were very
      good. MST was significantly correlated with VO2 peak (r = 0.79) and Wmax (r =
      0.84) but not with anthropometric measures. The MST walking distance improved
      significantly by 32.5%, ES 2.5. The attendance rate at the exercise sessions was
      excellent. CONCLUSION: This modular, varied aerobic training program has
      clinically relevant effects on aerobic performance in adolescents with severe
      obesity. The added value of our aerobic training program for body weight
      management programs for adolescents with severe obesity should be studied with a
      randomized trial. This study further demonstrated that the MST is a reliable,
      sensitive and easy to administer outcome measure for aerobic fitness in
      adolescent body weight management trials.

PMID- 17445259
TI  - Persistent activation of NF-kappaB related to IkappaB's degradation profiles
      during early chemical hepatocarcinogenesis.
AB  - BACKGROUND: To define the NF-kappaB activation in early stages of
      hepatocarcinogenesis and its IkappaB's degradation profiles in comparison to sole
      liver regeneration. METHODS: Western-blot and EMSA analyses were performed for
      the NF-kappaB activation. The transcriptional activity of NF-kappaB was
      determined by RT-PCR of the IkappaB-alpha mRNA. The IkappaB's degradation
      proteins were determined by Western-blot assay. RESULTS: We demonstrated the
      persistent activation of NF-kappaB during early stages of hepatocarcinogenesis,
      which reached maximal level 30 min after partial hepatectomy. The DNA binding and
      transcriptional activity of NF-kappaB, were sustained during early steps of
      hepatocarcinogenesis in comparison to only partial hepatectomy, which displayed a
      transitory NF-kappaB activation. In early stages of hepatocarcinogenesis, the
      IkappaB-alpha degradation turned out to be acute and transitory, but the low
      levels of IkappaB-beta persisted even 15 days after partial hepatectomy.
      Interestingly, IkappaB-beta degradation is not induced after sole partial
      hepatectomy. CONCLUSION: We propose that during liver regeneration, the
      transitory stimulation of the transcription factor response, assures blockade of
      NF-kappaB until recovery of the total mass of the liver and the persistent NF
      kappaB activation in early hepatocarcinogenesis may be due to IkappaB-beta and
      IkappaB-alpha degradation, mainly IkappaB-beta degradation, which contributes to
      gene transcription related to proliferation required for neoplastic progression.

PMID- 17445258
TI  - Immunomodulation by maternal autoantibodies of the fetal serotoninergic 5-HT4
      receptor and its consequences in early BALB/c mouse embryonic development.
AB  - BACKGROUND: The presence of functional 5-HT4 receptors in human and its
      involvement in neonatal lupus erythematosus (NLE) have prompted us to study the
      receptor expression and role during embryogenesis. Earlier we managed to
      demonstrate that female BALB/c mice immunized against the second extracellular
      loop (SEL) of the 5-HT4 receptor gave birth to pups with heart block. To explain
      this phenomenon we investigated the expression of 5-HT4 receptors during mouse
      embryogenesis. At the same time we looked whether the consequence of 5-HT4
      receptor immunomodulation observed earlier is in relation to receptor expression.
      We studied the expression of 5-HT4 receptor at the mRNA level and its two
      isoforms 5-HT4(a) and 5-HT4(d) at the protein level in embryos from BALB/c mice,
      at 8th, 12th, 18th gestation days (GD) and 1 day post natal (DPN). Simultaneously
      the receptor activity was inhibited by rising antibodies, in female mice against
      SEL of the receptor. The mice were mated and embryos were collected at 8th, 12th,
      18th GD and 1 DPN. RESULTS: 5-HT4 receptor mRNA increased in brain from 12th GD
      to 1 DPN. Its expression gradually decreased in heart and disappeared at birth.
      This was consistent with expression of the receptor isoforms 5-HT4(a) and (d).
      Abnormalities like decreased number of embryos, growth delay, spina bifida and
      sinus arrhythmia from 12th GD were documented in pups of mice showing anti-5-HT4
      receptor antibodies. CONCLUSION: serotoninergic 5-HT4 receptor plays an important
      role in mouse foetal development. In BALB/c mice there is a direct relation
      between the expression of receptor and the deleterious effect of maternal anti-5
      HT4 receptor autoantibodies in early embryogenesis.

PMID- 17445260
TI  - Potential barriers and facilitators for implementation of an integrated care
      pathway for hearing-impaired persons: an exploratory survey among patients and
      professionals.
AB  - BACKGROUND: Because of the increasing costs and anticipated shortage of Ear Nose
      and Throat (ENT) specialists in the care for hearing-impaired persons, an
      integrated care pathway that includes direct hearing aid provision was developed.
      While this direct pathway is still under investigation, in a survey we examined
      expectations and potential barriers and facilitators towards this direct pathway,
      of patients and professionals involved in the pathway. METHODS: Two study
      populations were assessed: members of the health professions involved in the care
      pathway for hearing-impaired persons (general practitioners (GPs), hearing aid
      dispensers, ENT-specialists and clinical audiologists) and persons with hearing
      complaints. We developed a comprehensive semi-structured questionnaire for the
      professionals, regarding expectations, barriers, facilitators and conditions for
      implementation. We developed two questionnaires for persons with hearing
      complaints, both regarding evaluations and preferences, and administered them
      after they had experienced two key elements of the direct pathway: the triage and
      the hearing aid fitting. RESULTS: On average GPs and hearing aid dispensers had
      positive expectations towards the direct pathway, while ENT-specialists and
      clinical audiologists had negative expectations. Professionals stated both
      barriers and facilitators towards the direct pathway. Most professionals either
      supported implementation of the direct pathway, provided that a number of
      conditions were satisfied, or did not support implementation, unless roughly the
      same conditions were satisfied. Professionals generally agreed on which
      conditions need to be satisfied. Persons with hearing complaints evaluated the
      present referral pathway and the new direct pathway equally. Many, especially
      older, participants stated however that they would still visit the GP and ENT
      specialist, even when this would not be necessary for reimbursement of the
      hearing aid, and found it important that the ENT-specialist or Audiological
      Centre evaluated their hearing aid. CONCLUSION: This study identified
      professional concerns about the direct pathway for hearing-impaired persons. Gaps
      exist in expectations amongst professions. Also gaps exist between users of the
      pathway, especially between age groups and regions. Professionals are united in
      the conditions that need to be fulfilled for a successful implementation of the
      direct pathway. Implementation on a regional level is recommended to best satisfy
      these conditions.

PMID- 17445261
TI  - A decline in transcript abundance for Heterodera glycines homologs of
      Caenorhabditis elegans uncoordinated genes accompanies its sedentary parasitic
      phase.
AB  - BACKGROUND: Heterodera glycines (soybean cyst nematode [SCN]), the major pathogen
      of Glycine max (soybean), undergoes muscle degradation (sarcopenia) as it becomes
      sedentary inside the root. Many genes encoding muscular and neuromuscular
      components belong to the uncoordinated (unc) family of genes originally
      identified in Caenorhabditis elegans. Previously, we reported a substantial
      decrease in transcript abundance for Hg-unc-87, the H. glycines homolog of unc-87
      (calponin) during the adult sedentary phase of SCN. These observations implied
      that changes in the expression of specific muscle genes occurred during
      sarcopenia. RESULTS: We developed a bioinformatics database that compares
      expressed sequence tag (est) and genomic data of C. elegans and H. glycines (CeHg
      database). We identify H. glycines homologs of C. elegans unc genes whose protein
      products are involved in muscle composition and regulation. RT-PCR reveals the
      transcript abundance of H. glycines unc homologs at mobile and sedentary stages
      of its lifecycle. A prominent reduction in transcript abundance occurs in samples
      from sedentary nematodes for homologs of actin, unc-60B (cofilin), unc-89, unc-15
      (paromyosin), unc-27 (troponin I), unc-54 (myosin), and the potassium channel unc
      110 (twk-18). Less reduction is observed for the focal adhesion complex gene Hg
      unc-97. CONCLUSION: The CeHg bioinformatics database is shown to be useful in
      identifying homologs of genes whose protein products perform roles in specific
      aspects of H. glycines muscle biology. Our bioinformatics comparison of C.
      elegans and H. glycines genomic data and our Hg-unc-87 expression experiments
      demonstrate that the transcript abundance of specific H. glycines homologs of
      muscle gene decreases as the nematode becomes sedentary inside the root during
      its parasitic feeding stages.

PMID- 17445262
TI  - Measurement and monitoring of electrocardiogram belt tension in premature infants
      for assessment of respiratory function.
AB  - BACKGROUND: Monitoring of the electrocardiogram (ECG) in premature infants with
      conventional adhesive-backed electrodes can harm their sensitive skin. Use of an
      electrode belt prevents skin irritation, but the effect of belt pressure on
      respiratory function is unknown. A strain gauge sensor is described which
      measures applied belt tension. METHOD: The device frame was comprised of an
      aluminum housing and slide to minimize the device weight. Velcro tabs connected
      housing and slide to opposite tabs located at the electrode belt ends. The slide
      was connected to a leaf spring, to which were bonded two piezoresistive
      transducers in a half-bridge circuit configuration. The device was tested for
      linearity and calibrated. The effect on infant respiratory function of constant
      belt tension in the normal range (30 g-90 g) was determined. RESULTS: The
      mechanical response to a step input was second order (fn = 401 Hz, zeta = 0.08).
      The relationship between applied tension and output voltage was linear in the
      range 25-225 gm of applied tension (r2 = 0.99). Measured device sensitivity was
      2.18 mV/gm tension using a 5 V bridge excitation voltage. When belt tension was
      increased in the normal range from 30 gm to 90 gm, there was no significant
      change in heart rate and most respiratory functions during monitoring. At an
      intermediate level of tension of 50 gm, pulmonary resistance and work of
      breathing significantly decreased. CONCLUSION: The mechanical and electrical
      design of a device for monitoring electrocardiogram electrode belt tension is
      described. Within the typical range of application tension, cardiovascular and
      respiratory function are not substantially negatively affected by electrode belt
      force.

PMID- 17445263
TI  - The training and expectations of medical students in Mozambique.
AB  - BACKGROUND: This paper describes the socio-economic profile of medical students
      in the 1998/99 academic year at the Universidade Eduardo Mondlane (UEM) Medical
      Faculty in Maputo. It aims to identify their social and geographical origins in
      addition to their expectations and difficulties regarding their education and
      professional future. METHODS: The data were collected through a questionnaire
      administered to all medical students at the faculty. RESULTS: Although most
      medical students were from outside Maputo City and Maputo Province, expectations
      of getting into medical school were already associated with a migration from the
      periphery to the capital city, even before entering medical education. This lays
      the basis for the concentration of physicians in the capital city once their term
      of compulsory rural employment as junior doctors is completed. The decision to
      become a doctor was taken at an early age. Close relatives, or family friends
      seem to have been an especially important variable in encouraging, reinforcing
      and promoting the desire to be a doctor. The academic performance of medical
      students was dismal. This seems to be related to several difficulties such as
      lack of library facilities, inadequate financial support, as well as poor high
      school preparation. Only one fifth of the students reported receiving financial
      support from the Mozambican government to subsidize their medical studies.
      CONCLUSION: Medical students seem to know that they will be needed in the public
      sector, and that this represents an opportunity to contribute to the public's
      welfare. Nevertheless, their expectations are, already as medical students, to
      combine their public sector practice with private medical work in order to
      improve their earnings.

PMID- 17445264
TI  - Prevalence and risk factors for HIV-1 infection in rural Kilimanjaro region of
      Tanzania: implications for prevention and treatment.
AB  - BACKGROUND: Variability in stages of the HIV-1 epidemic and hence HIV-1
      prevalence exists in different areas in sub-Saharan Africa. The purpose of this
      study was to investigate the magnitude of HIV-1 infection and identify HIV-1 risk
      factors that may help to develop preventive strategies in rural Kilimanjaro,
      Tanzania. METHODS: A cross-sectional study was conducted between March and May of
      2005 involving all individuals aged between 15-44 years having an address in Oria
      Village. All eligible individuals were registered and invited to participate.
      Participants were interviewed regarding their demographic characteristics, sexual
      behaviors, and medical history. Following a pre-test counseling, participants
      were offered an HIV test. RESULTS: Of the 2 093 eligible individuals, 1 528
      (73.0%) participated. The overall age and sex adjusted HIV-1 prevalence was 5.6%.
      Women had 2.5 times higher prevalence (8.0% vs. 3.2%) as compared to men. The age
      group 25-44 years, marriage, separation and low education were associated with
      higher risk of HIV-1 infection for both sexes. HIV-1 infection was significantly
      associated with >2 sexual partners in the past 12 months (women: Adjusted odds
      ratio [AOR], 2.5 (95%CI: 1.3-4.7), and past 5 years, [(men: AOR, 2.2 (95%CI:1.2
      5.6); women: AOR, 2.5 (95%CI: 1.4-4.0)], unprotected casual sex (men: AOR,1.8
      95%CI: 1.2-5.8), bottled alcohol (Men: AOR, 5.9 (95%CI:1.7-20.1) and local brew
      (men: AOR, 3.7 (95%CI: 1.5-9.2). Other factors included treatment for genital
      ulcers and genital discharge in the past 1 month. Health-related complaints were
      more common among HIV-1 seropositive as compared to seronegative participants and
      predicted the presence of HIV-1 infection. CONCLUSION: HIV-1 infection was highly
      prevalent in this population. As compared to our previous findings, a shift of
      the epidemic from a younger to an older age group and from educated to uneducated
      individuals was observed. Women and married or separated individuals remained at
      higher risk of infection. To prevent further escalation of the HIV epidemic,
      efforts to scale up HIV prevention programmes addressing females, people with low
      education, lower age at marriage, alcohol consumption, condom use and multiple
      sexual partners for all age groups remains a top priority. Care and treatment are
      urgently needed for those infected in rural areas.

PMID- 17445265
TI  - Putative null distributions corresponding to tests of differential expression in
      the Golden Spike dataset are intensity dependent.
AB  - BACKGROUND: We provide a re-analysis of the Golden Spike dataset, a first
      generation "spike-in" control microarray dataset. The original analysis of the
      Golden Spike dataset was presented in a manuscript by Choe et al. and raised
      questions concerning the performance of several statistical methods for the
      control of the false discovery rate (across a set of tests for differential
      expression). These original findings are now in question as it has been reported
      that the p-values associated with the tests of differential expression for null
      probesets (i.e., probesets designed to be fold change 1 across the two arms of
      the experiment) are not uniformly distributed. Two recent publications have
      speculated as to the reasons the null distributions are non-uniform. A
      publication by Dabney and Storey concludes that the non-uniform distributions of
      null p-values are the direct consequence of an experimental design which requires
      technical replicates to approximate biological replicates. Irizarry et al.
      identify four characteristics of the feature level data (three related to
      experimental design and one artifact). Irizarry et al. argue that the four
      observed characteristics imply that the assumptions common to most pre-processing
      algorithms are not satisfied and hence the expression measure methodologies
      considered by Choe et al. are likely to be flawed. RESULTS: We replicate and
      extend the analyses of Dabney and Storey and present our results in the context
      of a two stage analysis. We provide evidence that the Stage I pre-processing
      algorithms considered in Dabney and Storey fail to provide expression values that
      are adequately centered or scaled. Furthermore, we demonstrate that the
      distributions of the p-values, test statistics, and probabilities associated with
      the relative locations and variabilities of the Stage II expression values vary
      with signal intensity. We provide diagnostic plots and a simple logistic
      regression based test statistic to detect these intensity related defects in the
      processed data. CONCLUSION: We agree with Dabney and Storey that the null p
      values considered in Choe et al. are indeed non-uniform. We also agree with the
      conclusion that, given current pre-processing technologies, the Golden Spike
      dataset should not serve as a reference dataset to evaluate false discovery rate
      controlling methodologies. However, we disagree with the assessment that the non
      uniform p-values are merely the byproduct of testing for differential expression
      under the incorrect assumption that chip data are approximate to biological
      replicates. Whereas Dabney and Storey attribute the non-uniform p-values to
      violations of the Stage II model assumptions, we provide evidence that the non
      uniformity can be attributed to the failure of the Stage I analyses to correct
      for systematic biases in the raw data matrix. Although we do not speculate as to
      the root cause of these systematic biases, the observations made in Irizarry et
      al. appear to be consistent with our findings. Whereas Irizarry et al. describe
      the effect of the experimental design on the feature level data, we consider the
      effect on the underlying multivariate distribution of putative null p-values. We
      demonstrate that the putative null distributions corresponding to the pre
      processing algorithms considered in Choe et al. are all intensity dependent. This
      dependence serves to invalidate statistical inference based upon standard two
      sample test statistics. We identify a flaw in the characterization of the
      appropriate "null" probesets described in Choe et al. and we provide a corrected
      analysis which reduces (but does not eliminate) the intensity dependent effects.

PMID- 17445266
TI  - In-vivo kinetics of inhaled 5-aminolevulinic acid-induced protoporphyrin IX
      fluorescence in bronchial tissue.
AB  - BACKGROUND: In the diagnosis of early-stage lung cancer photosensitizer-enhanced
      fluorescence bronchoscopy with inhaled 5-aminolevolinic acid (5-ALA) increases
      sensitivity when compared to white-light bronchoscopy. This investigation was to
      evaluate the in vivo tissue pharmacokinetics of inhaled 5-ALA within the
      bronchial mucosa in order to define the time optimum for its application prior to
      bronchoscopy. METHODS: Patients with known or suspected bronchial carcinoma were
      randomized to receive 200 mg 5-ALA via inhalation 1, 2, 3, 4 or 6 hours before
      flexible fluorescence bronchoscopy was performed. Macroscopically suspicious
      areas as well as areas with visually detected porphyrin fluorescence and normal
      control sites were measured spectroscopically. Biopsies for histopathology were
      obtained from suspicious areas as well as from adjacent normal areas. RESULTS:
      Fluorescence bronchoscopy performed in 19 patients reveals a sensitivity for
      malignant and premalignant changes (moderate dysplasia) which is almost twice as
      high as that of white-light bronchoscopy, whereas specificity is reduced. This is
      due to false-positive inflammatory lesions which also frequently show increased
      porphyrin fluorescence. Malignant and premalignant alterations produced
      fluorescence values that are up to 5 times higher than those of normal tissue.
      According to the pharmacokinetics of porphyrin fluorescence measured by
      spectroscopy, the optimum time range for 5-ALA application is 80-270 min prior to
      fluorescence bronchoscopy, with an optimum at 160 min. CONCLUSION: According to
      our results we propose inhalation of 5-ALA 160 min prior to fluorescence
      bronchoscopy, suggesting that this time difference provides the best tumor/normal
      tissue fluorescence ratio.

PMID- 17445267
TI  - Incidence of cancer in children residing in ten jurisdictions of the Mexican
      Republic: importance of the Cancer registry (a population-based study).
AB  - BACKGROUND: In 1996, Mexico started to register cases of childhood cancer. Here,
      we describe the incidence of cancer in children, residing in ten Mexican
      jurisdictions, who were treated by the Instituto Mexicano del Seguro Social
      (IMSS). METHODS: New cases of childhood cancer, which were registered
      prospectively in nine principal Medical Centers of IMSS during the periods 1998
      2000 (five jurisdictions) and 1996-2002 (five jurisdictions), were analyzed.
      Personnel were specifically trained to register, capture, and encode information.
      For each of these jurisdictions, the frequency, average annual age-standardized
      incidence (AAS) and average annual incidence per period by sex and, age, were
      calculated (rates per 1,000,000 children/years). RESULTS: In total 2,615 new
      cases of cancer were registered, with the male/female ratio generally >1, but in
      some tumors there were more cases in females (retinoblastoma, germ cells tumors).
      The principal groups of neoplasms in seven jurisdictions were leukemias, central
      nervous system tumors (CNS tumors), and lymphomas, and the combined frequency for
      these three groups was 62.6 to 77.2%. Most frequently found (five jurisdictions)
      was the North American-European pattern (leukemias-CNS tumors-lymphomas). Eight
      jurisdictions had AAS within the range reported in the world literature. The
      highest incidence was found for children underless than five year of age. In
      eight jurisdictions, leukemia had high incidence (>50). The AAS of lymphomas was
      between 1.9 to 28.6. Chiapas and Guerrero had the highest AAS of CNS tumors (31.9
      and 30.3, respectively). The frequency and incidence of neuroblastoma was low.
      Chiapas had the highest incidence of retinoblastoma (21.8). Germ-cell tumors had
      high incidence. CONCLUSION: The North American-European pattern of cancers was
      the principal one found; the overall incidence was within the range reported
      worldwide. In general but particularly in two jurisdictions (Yucatan and
      Chiapas), it will be necessary to carry out studies concerning the causes of
      cancer in children. Due to the little that is known about the incidence of cancer
      in Mexican children, it will be necessary to develop a national program to
      establish a cancer registry for the whole of the country.

PMID- 17445268
TI  - Coordinate regulation of DNA methyltransferase expression during oogenesis.
AB  - BACKGROUND: Normal mammalian development requires the action of DNA
      methyltransferases (DNMTs) for the establishment and maintenance of DNA
      methylation within repeat elements and imprinted genes. Here we report the
      expression dynamics of Dnmt3a and Dnmt3b, as well as a regulator of DNA
      methylation, Dnmt3L, in isolated female germ cells. RESULTS: Our results indicate
      that these enzymes are coordinately regulated and that their expression peaks
      during the stage of postnatal oocyte development when maternal methylation
      imprints are established. We find that Dnmt3a, Dnmt3b, Dnmt3L and Dnmt1o
      transcript accumulation is related to oocyte diameter. Furthermore, DNMT3L
      deficient 15 dpp oocytes have aberrantly methylated Snrpn, Peg3 and Igf2r DMRs,
      but normal IAP and LINE-1 methylation levels, thereby highlighting a male germ
      cell specific role for DNMT3L in the establishment of DNA methylation at repeat
      elements. Finally, real-time RT-PCR analysis indicates that the depletion of
      either DNMT3L or DNMT1o in growing oocytes results in the increased expression of
      the de novo methyltransferase Dnmt3b, suggesting a potential compensation
      mechanism by this enzyme for the loss of one of the other DNA methyltransferases.
      CONCLUSION: Together these results provide a better understanding of the
      developmental regulation of Dnmt3a, Dnmt3b and Dnmt3L at the time of de novo
      methylation during oogenesis and demonstrate that the involvement of DNMT3L in
      retrotransposon silencing is restricted to the male germ line. This in turn
      suggests the existence of other factors in the oocyte that direct DNA methylation
      to transposons.

PMID- 17445269
TI  - Novel insights into RNAi off-target effects using C. elegans paralogs.
AB  - BACKGROUND: In the few years since its discovery, RNAi has turned into a very
      powerful tool for the study of gene function by allowing post-transcriptional
      gene silencing. The RNAi mechanism, which is based on the introduction of a
      double-stranded RNA (dsRNA) trigger whose sequence is similar to that of the
      targeted messenger RNA (mRNA), is subject to off-target cross-reaction. RESULTS:
      We use a novel strategy based on phenotypic analysis of paralogs and predict
      that, in Caenorhabditis elegans, off-target effects occur when an mRNA sequence
      shares more than 95% identity over 40 nucleotides with the dsRNA. Interestingly,
      our results suggest that the minimum length necessary of a high-similarity
      stretch between a dsRNA and its target in order to observe an efficient RNAi
      effect varies from 30 to 50 nucleotides rather than 22 nucleotides, which is the
      length of siRNAs in C. elegans. CONCLUSION: Our predictive methods would improve
      the design of dsRNA and ultimately the use of RNAi as a therapeutic tool upon
      experimental verification.

PMID- 17445270
TI  - Changes in pulse pressure variability during cardiac resynchronization therapy in
      mechanically ventilated patients.
AB  - INTRODUCTION: The respiratory variation in pulse pressure (PP) has been
      established as a dynamic variable of cardiac preload which indicates fluid
      responsiveness in mechanically ventilated patients. The impact of acute changes
      in cardiac performance on respiratory fluctuations in PP has not been evaluated
      until now. We used cardiac resynchronization therapy as a model to assess the
      acute effects of changes in left ventricular performance on respiratory PP
      variability without the need of pharmacological intervention. METHODS: In 19
      patients undergoing the implantation of a biventricular pacing/defibrillator
      device under general anesthesia, dynamic blood pressure regulation was assessed
      during right ventricular and biventricular pacing in the frequency domain (power
      spectral analysis) and in the time domain (PP variation: difference between the
      maximal and minimal PP values, normalized by the mean value). RESULTS: PP
      increased slightly during biventricular pacing but without statistical
      significance (right ventricular pacing, 33 +/- 10 mm Hg; biventricular pacing, 35
      +/- 11 mm Hg). Respiratory PP fluctuations increased significantly
      (logarithmically transformed PP variability -1.27 +/- 1.74 ln mm Hg2 versus -0.66
      +/- 1.48 ln mm Hg2; p < 0.01); the geometric mean of respiratory PP variability
      increased 1.8-fold during cardiac resynchronization. PP variation, assessed in
      the time domain and expressed as a percentage, showed comparable changes,
      increasing from 5.3% (3.1%; 12.3%) during right ventricular pacing to 6.9% (4.7%;
      16.4%) during biventricular pacing (median [25th percentile; 75th percentile]; p
      < 0.01). CONCLUSION: Changes in cardiac performance have a significant impact on
      respiratory hemodynamic fluctuations in ventilated patients. This influence
      should be taken into consideration when interpreting PP variation.

PMID- 17445271
TI  - Analysis of sequence variations in the suppressor of cytokine signaling (SOCS)-3
      gene in extremely obese children and adolescents.
AB  - BACKGROUND: The suppressor of cytokine signaling (SOCS)-3 is a negative feedback
      regulator of cytokine signaling and also influences leptin signaling. We
      investigated association of variations in the coding sequence and promoter region
      of SOCS3 with extreme obesity in German children and adolescents. METHODS: An
      initial screen for sequence variations in 181 extremely obese children and
      adolescents and 188 healthy underweight adults revealed two previously reported
      single nucleotide polymorphisms (SNPs) in the SOCS3 5' region: -1044 C>A
      (numbering refers to bases upstream of ATG in exon 2) within a predicted STAT3
      binding element and -920 C>A (rs12953258, for numbering, see above). RESULTS: We
      did not detect significant differences in allele or genotype frequencies for any
      of these SNPs between the analysed study groups (all nominal p > 0.2). In
      addition, we performed a pedigree transmission disequilibrium test (PDT) for the
      SNP -1044 C>A in families comprising 703 obese children and adolescents, 281 of
      their obese siblings and both biological parents. The PDT revealed no
      transmission disequilibrium (nominal p > 0.05). CONCLUSION: In conclusion, our
      data do not suggest evidence for a major role of the respective SNPs in SOCS3 in
      the pathogenesis of extreme obesity in our study groups.

PMID- 17445272
TI  - CGKB: an annotation knowledge base for cowpea (Vigna unguiculata L.) methylation
      filtered genomic genespace sequences.
AB  - BACKGROUND: Cowpea [Vigna unguiculata (L.) Walp.] is one of the most important
      food and forage legumes in the semi-arid tropics because of its ability to
      tolerate drought and grow on poor soils. It is cultivated mostly by poor farmers
      in developing countries, with 80% of production taking place in the dry savannah
      of tropical West and Central Africa. Cowpea is largely an underexploited crop
      with relatively little genomic information available for use in applied plant
      breeding. The goal of the Cowpea Genomics Initiative (CGI), funded by the
      Kirkhouse Trust, a UK-based charitable organization, is to leverage modern
      molecular genetic tools for gene discovery and cowpea improvement. One aspect of
      the initiative is the sequencing of the gene-rich region of the cowpea genome
      (termed the genespace) recovered using methylation filtration technology and
      providing annotation and analysis of the sequence data. DESCRIPTION: CGKB, Cowpea
      Genespace/Genomics Knowledge Base, is an annotation knowledge base developed
      under the CGI. The database is based on information derived from 298,848 cowpea
      genespace sequences (GSS) isolated by methylation filtering of genomic DNA. The
      CGKB consists of three knowledge bases: GSS annotation and comparative genomics
      knowledge base, GSS enzyme and metabolic pathway knowledge base, and GSS simple
      sequence repeats (SSRs) knowledge base for molecular marker discovery. A homology
      based approach was applied for annotations of the GSS, mainly using BLASTX
      against four public FASTA formatted protein databases (NCBI GenBank Proteins,
      UniProtKB-Swiss-Prot, UniprotKB-PIR (Protein Information Resource), and UniProtKB
      TrEMBL). Comparative genome analysis was done by BLASTX searches of the cowpea
      GSS against four plant proteomes from Arabidopsis thaliana, Oryza sativa,
      Medicago truncatula, and Populus trichocarpa. The possible exons and introns on
      each cowpea GSS were predicted using the HMM-based Genscan gene predication
      program and the potential domains on annotated GSS were analyzed using the HMMER
      package against the Pfam database. The annotated GSS were also assigned with Gene
      Ontology annotation terms and integrated with 228 curated plant metabolic
      pathways from the Arabidopsis Information Resource (TAIR) knowledge base. The
      UniProtKB-Swiss-Prot ENZYME database was used to assign putative enzymatic
      function to each GSS. Each GSS was also analyzed with the Tandem Repeat Finder
      (TRF) program in order to identify potential SSRs for molecular marker discovery.
      The raw sequence data, processed annotation, and SSR results were stored in
      relational tables designed in key-value pair fashion using a PostgreSQL
      relational database management system. The biological knowledge derived from the
      sequence data and processed results are represented as views or materialized
      views in the relational database management system. All materialized views are
      indexed for quick data access and retrieval. Data processing and analysis
      pipelines were implemented using the Perl programming language. The web interface
      was implemented in JavaScript and Perl CGI running on an Apache web server. The
      CPU intensive data processing and analysis pipelines were run on a computer
      cluster of more than 30 dual-processor Apple XServes. A job management system
      called Vela was created as a robust way to submit large numbers of jobs to the
      Portable Batch System (PBS). CONCLUSION: CGKB is an integrated and annotated
      resource for cowpea GSS with features of homology-based and HMM-based
      annotations, enzyme and pathway annotations, GO term annotation, toolkits, and a
      large number of other facilities to perform complex queries. The cowpea GSS,
      chloroplast sequences, mitochondrial sequences, retroelements, and SSR sequences
      are available as FASTA formatted files and downloadable at CGKB. This database
      and web interface are publicly accessible at
      http://cowpeagenomics.med.virginia.edu/CGKB/.

PMID- 17445274
TI  - Report on BrainChild hydrocephalus conference.
AB  - A report of a meeting sponsored by the BrainChild Foundation on the challenges
      for hydrocephalus researchers to provide the information required for better
      management of cerebrospinal fluid disorders.

PMID- 17445273
TI  - Efficient pairwise RNA structure prediction using probabilistic alignment
      constraints in Dynalign.
AB  - BACKGROUND: Joint alignment and secondary structure prediction of two RNA
      sequences can significantly improve the accuracy of the structural predictions.
      Methods addressing this problem, however, are forced to employ constraints that
      reduce computation by restricting the alignments and/or structures (i.e. folds)
      that are permissible. In this paper, a new methodology is presented for the
      purpose of establishing alignment constraints based on nucleotide alignment and
      insertion posterior probabilities. Using a hidden Markov model, posterior
      probabilities of alignment and insertion are computed for all possible pairings
      of nucleotide positions from the two sequences. These alignment and insertion
      posterior probabilities are additively combined to obtain probabilities of co
      incidence for nucleotide position pairs. A suitable alignment constraint is
      obtained by thresholding the co-incidence probabilities. The constraint is
      integrated with Dynalign, a free energy minimization algorithm for joint
      alignment and secondary structure prediction. The resulting method is benchmarked
      against the previous version of Dynalign and against other programs for pairwise
      RNA structure prediction. RESULTS: The proposed technique eliminates manual
      parameter selection in Dynalign and provides significant computational time
      savings in comparison to prior constraints in Dynalign while simultaneously
      providing a small improvement in the structural prediction accuracy. Savings are
      also realized in memory. In experiments over a 5S RNA dataset with average
      sequence length of approximately 120 nucleotides, the method reduces computation
      by a factor of 2. The method performs favorably in comparison to other programs
      for pairwise RNA structure prediction: yielding better accuracy, on average, and
      requiring significantly lesser computational resources. CONCLUSION: Probabilistic
      analysis can be utilized in order to automate the determination of alignment
      constraints for pairwise RNA structure prediction methods in a principled
      fashion. These constraints can reduce the computational and memory requirements
      of these methods while maintaining or improving their accuracy of structural
      prediction. This extends the practical reach of these methods to longer length
      sequences. The revised Dynalign code is freely available for download.

PMID- 17445275
TI  - The strike rate index: a new index for journal quality based on journal size and
      the h-index of citations.
AB  - Quantifying the impact of scientific research is almost always controversial, and
      there is a need for a uniform method that can be applied across all fields.
      Increasingly, however, the quantification has been summed up in the impact factor
      of the journal in which the work is published, which is known to show differences
      between fields. Here the h-index, a way to summarize an individual's highly cited
      work, was calculated for journals over a twenty year time span and compared to
      the size of the journal in four fields, Agriculture, Condensed Matter Physics,
      Genetics and Heredity and Mathematical Physics. There is a linear log-log
      relationship between the h-index and the size of the journal: the larger the
      journal, the more likely it is to have a high h-index. The four fields cannot be
      separated from each other suggesting that this relationship applies to all
      fields. A strike rate index (SRI) based on the log relationship of the h-index
      and the size of the journal shows a similar distribution in the four fields, with
      similar thresholds for quality, allowing journals across diverse fields to be
      compared to each other. The SRI explains more than four times the variation in
      citation counts compared to the impact factor.

PMID- 17445276
TI  - Structure of alpha-conotoxin BuIA: influences of disulfide connectivity on
      structural dynamics.
AB  - BACKGROUND: Alpha-conotoxins have exciting therapeutic potential based on their
      high selectivity and affinity for nicotinic acetylcholine receptors. The spacing
      between the cysteine residues in alpha-conotoxins is variable, leading to the
      classification of sub-families. BuIA is the only alpha-conotoxin containing a 4/4
      cysteine spacing and thus it is of significant interest to examine the structure
      of this conotoxin. RESULTS: In the current study we show the native globular
      disulfide connectivity of BuIA displays multiple conformations in solution
      whereas the non-native ribbon isomer has a single well-defined conformation.
      Despite having multiple conformations in solution the globular form of BuIA
      displays activity at the nicotinic acetylcholine receptor, contrasting with the
      lack of activity of the structurally well-defined ribbon isomer. CONCLUSION:
      These findings are opposite to the general trends observed for alpha-conotoxins
      where the native isomers have well-defined structures and the ribbon isomers are
      generally disordered. This study thus highlights the influence of the disulfide
      connectivity of BuIA on the dynamics of the three-dimensional structure.

PMID- 17445277
TI  - Immunohistochemical expression of melan-A and tyrosinase in uveal melanoma.
AB  - BACKGROUND: Melan-A and tyrosinase are new immunohistochemical markers that can
      be used in the diagnosis of melanocytic lesions. The aim of this study was to
      investigate the correlation between radiotherapy or clinicohistopathological
      parameters and the expression of melan-A and tyrosinase in uveal melanoma.
      METHODS: Thirty-six enucleated cases of uveal melanoma were studied. The formalin
      fixed, paraffin-embedded specimens were immunostained with monoclonal antibodies
      against melan-A and tyrosinase. The samples were classified as either positive or
      negative. The chi-square or the Student-t tests were used to test for the
      correlation of the expression rates of melan-A and tyrosinase with clinico
      pathological parameters. RESULTS: Melan-A and tyrosinase were positive in 33
      (91.7%) and 35 (97.2%) of the specimens, respectively. There was no significant
      association between the expression of melan-A or tyrosinase and radiotherapy or
      any clinico-pathological parameter. All specimens were positive for at least one
      of the immunohistochemical markers. CONCLUSION: To the best of our knowledge this
      is the first study concluding that the expression of melanocytic markers such as
      melan-A and tyrosinase is not influenced by radiotherapy or any clinico
      pathological parameter. Moreover, when tyrosinase and melan-A are used together,
      100% of the formalin-fixed, paraffin-embedded uveal melanoma samples tested
      positive for one of those markers.

PMID- 17445278
TI  - Association between the DTNBP1 gene and intelligence: a case-control study in
      young patients with schizophrenia and related disorders and unaffected siblings.
AB  - BACKGROUND: The dystrobrevin-binding protein 1 (DTNBP1) gene is a susceptibility
      gene for schizophrenia. There is growing evidence that DTNPB1 contributes to
      intelligence and cognition. In this study, we investigated association between
      single nucleotide polymorphisms (SNPs) in the DTNBP1 gene and intellectual
      functioning in patients with a first episode of schizophrenia or related
      psychotic disorder (first-episode psychosis, FEP), their healthy siblings, and
      unrelated controls. METHODS: From all subjects IQ measurements were obtained
      (verbal IQ [VIQ], performance IQ [PIQ], and full scale IQ [FSIQ]). Seven SNPs in
      the DTNBP1 gene were genotyped using single base primer extension and analyzed by
      matrix-assisted laser deionization mass spectrometry (MALDI-TOF). RESULTS: Mean
      VIQ, PIQ, and FSIQ scores differed significantly (p < 0.001) between patients,
      siblings, and controls. Using a family-based and a case-control design, several
      single SNPs were significantly associated with IQ scores in patients, siblings,
      and controls. CONCLUSION: Although preliminary, our results provide evidence for
      association between the DTNBP1 gene and intelligence in patients with FEP and
      their unaffected siblings. Genetic variation in the DTNBP1 gene may increase
      schizophrenia susceptibility by affecting intellectual functioning.

PMID- 17445279
TI  - Deciphering the molecular machinery of stem cells: a look at the neoblast gene
      expression profile.
AB  - BACKGROUND: Mammalian stem cells are difficult to access experimentally; model
      systems that can regenerate offer an alternative way to characterize stem cell
      related genes. Planarian regeneration depends on adult pluripotent stem cells-
      the neoblasts. These cells can be selectively destroyed using X-rays, enabling
      comparison of organisms lacking stem cells with wild-type worms. RESULTS: Using a
      genomic approach we produced an oligonucleotide microarray chip (the Dj600 chip),
      which was designed using selected planarian gene sequences. Using this chip, we
      compared planarians treated with high doses of X-rays (which eliminates all
      neoblasts) with wild-type worms, which led to identification of a set of
      putatively neoblast-restricted genes. Most of these genes are involved in
      chromatin modeling and RNA metabolism, suggesting that epigenetic modifications
      and post-transcriptional regulation are pivotal in neoblast regulation. Comparing
      planarians treated with low doses of X-rays (after which some radiotolerant
      neoblasts re-populate the planarian body) with specimens irradiated with high
      doses and unirradiated control worms, we identified a group of genes that were
      upregulated as a consequence of low-dose X-ray treatment. Most of these genes
      encode proteins that are known to regulate the balance between death and survival
      of the cell; our results thus suggest that genetic programs that control neoblast
      cytoprotection, proliferation, and migration are activated by low-dose X-rays.
      CONCLUSION: The broad differentiation potential of planarian neoblasts is
      unparalleled by any adult stem cells in the animal kingdom. In addition to our
      validation of the Dj600 chip as a valuable platform, our work contributes to
      elucidating the molecular mechanisms that regulate the self-renewal and
      differentiation of neoblasts.

PMID- 17445280
TI  - Statistical significance of quantitative PCR.
AB  - BACKGROUND: PCR has the potential to detect and precisely quantify specific DNA
      sequences, but it is not yet often used as a fully quantitative method. A number
      of data collection and processing strategies have been described for the
      implementation of quantitative PCR. However, they can be experimentally
      cumbersome, their relative performances have not been evaluated systematically,
      and they often remain poorly validated statistically and/or experimentally. In
      this study, we evaluated the performance of known methods, and compared them with
      newly developed data processing strategies in terms of resolution, precision and
      robustness. RESULTS: Our results indicate that simple methods that do not rely on
      the estimation of the efficiency of the PCR amplification may provide
      reproducible and sensitive data, but that they do not quantify DNA with
      precision. Other evaluated methods based on sigmoidal or exponential curve
      fitting were generally of both poor resolution and precision. A statistical
      analysis of the parameters that influence efficiency indicated that it depends
      mostly on the selected amplicon and to a lesser extent on the particular
      biological sample analyzed. Thus, we devised various strategies based on
      individual or averaged efficiency values, which were used to assess the regulated
      expression of several genes in response to a growth factor. CONCLUSION: Overall,
      qPCR data analysis methods differ significantly in their performance, and this
      analysis identifies methods that provide DNA quantification estimates of high
      precision, robustness and reliability. These methods allow reliable estimations
      of relative expression ratio of two-fold or higher, and our analysis provides an
      estimation of the number of biological samples that have to be analyzed to
      achieve a given precision.

PMID- 17445281
TI  - Suicide and occupation: the impact of socio-economic, demographic and psychiatric
      differences.
AB  - BACKGROUND: To explore the risk of suicide associated with occupation while
      evaluating the impact of socio-economic, demographic and psychiatric differences.
      METHOD: A nested case-control study with 3195 suicides and 63 900 matched
      controls. Information on causes of death, occupation, psychiatric admission,
      marital status and socio-economic factors was obtained from routine registers.
      RESULTS: Across the 55 occupations investigated, the risk of suicide ranged from
      2.73 [95% confidence interval (CI) 1.77-4.22] among doctors to 0.44 (95% CI 0.27
      0.72) among architects and engineers compared with primary school teachers. With
      the exception of doctors and nurses, most of the excess risk of suicide
      associated with particular occupations is explained by the social and economic
      characteristics of people in those occupations. Much, but not all, of the excess
      risk in doctors and nurses is due to their increased use of self-poisoning, a
      method for which they have the knowledge to use effectively. Occupation has
      little association with suicide among people who suffer from a psychiatric
      illness, except for doctors, where the excess risk is 3.62 (p=0.007).
      CONCLUSIONS: Most of the considerable variation in suicide risk across
      occupations is explained by socio-economic factors, except for doctors and
      nurses. Apart from in doctors, the risk of suicide has little association with
      occupation among people who suffer from a psychiatric illness. Restriction of
      access to lethal means is an important strategy in suicide prevention.

PMID- 17445282
TI  - The clinical significance criterion in DSM-IV post-traumatic stress disorder.
AB  - BACKGROUND: The DSM-IV definition of post-traumatic stress disorder (PTSD)
      requires that the syndrome cause clinically significant distress or impairment.
      The impact of the clinical significance criterion on the lifetime prevalence of
      PTSD among civilian victims of traumatic events has not been evaluated. METHOD:
      Data from two community-based samples were examined, the 1996 Detroit Area Survey
      of Trauma (n=2181) and the Mid-Atlantic Urban Youth Study (n=1698). The World
      Health Organization Composite International Diagnostic Interview (WHO CIDI) was
      used to ascertain DSM-IV PTSD. RESULTS: The inclusion of the clinical
      significance criterion in DSM-IV reduces the conditional probability of PTSD
      given exposure to trauma by approximately 30%. Cases with clinically significant
      syndrome showed more pervasive and persistent disturbance and an excess in
      impaired activity days. CONCLUSIONS: The consistency of the findings between the
      two studies strengthens the evidence on the impact of the clinical significance
      criterion in the diagnosis of PTSD, and the construct validity of its
      measurement. There is a need for greater research effort on the definition and
      measurement of the clinical significance criterion.

PMID- 17445284
TI  - The effects of concentrated barley beta-glucan on blood lipids in a population of
      hypercholesterolaemic men and women.
AB  - Barley, like oats, is a rich source of the soluble fibre beta-glucan, which has
      been shown to significantly lower LDL-cholesterol (LDL-C). However, barley foods
      have been less widely studied. Therefore, we evaluated the LDL-C-lowering effect
      of a concentrated barley beta-glucan (BBG) extract as a vehicle to deliver this
      potential health benefit of barley. In a 10-week blinded controlled study,
      subjects were randomized to one of four treatment groups or control. Treatment
      groups included either high molecular weight (HMW) or low molecular weight (LMW)
      BBG at both 3 and 5 g doses. Treatment was delivered twice per day with meals in
      the form of two functional food products: a ready-to-eat cereal and a reduced
      calorie fruit juice beverage. Levels of total cholesterol, LDL-C, HDL-cholesterol
      (HDL-C), and TAG were determined at baseline and after 6 weeks of treatment. The
      study group comprised 155 subjects. All treatments were well tolerated and after
      6 weeks of treatment the mean LDL-C levels fell by 15 % in the 5 g HMW group, 13
      % in the 5 g LMW group and 9 % in both the 3 g/d groups, versus baseline. Similar
      results were observed for total cholesterol. HDL-C levels were unchanged by
      treatment. Concentrated BBG significantly improves LDL-C and total cholesterol
      among moderately dyslipidaemic subjects. Food products containing concentrated
      BBG should be considered an effective option for improving blood lipids.

PMID- 17445283
TI  - Longitudinal modeling of genetic and environmental influences on self-reported
      availability of psychoactive substances: alcohol, cigarettes, marijuana, cocaine
      and stimulants.
AB  - BACKGROUND: Although an obvious environmental factor influencing drug use, the
      sources of individual differences in drug availability (DA) are unknown. METHOD:
      This report is based on 1788 adult males from the Mid-Atlantic Twin Registry who
      participated in a structured telephone interview that included retrospective
      assessments of DA (cigarette, alcohol, marijuana, cocaine and stimulants) between
      ages 8 and 25. We fitted a biometric dual change score (DCS) model, adapted for
      ordinal data, to model latent growth and estimate the genetic and environmental
      components of variance over time. RESULTS: DA, despite being considered an
      environmental risk factor, is under both genetic and environmental control. For
      cigarette, alcohol, marijuana and cocaine availability, there was an overall
      increase in additive genetic variance and a decline in shared environmental
      variance over time. Non-shared environmental variance remained steady. Stimulant
      availability did not follow this pattern. Instead, there was an upswing in shared
      environmental effects with increasing age. CONCLUSION: We have modeled the
      genetic and environmental architecture of changes in DA across adolescence. The
      rise in additive genetic variance over time coincides with acceleration in the
      expression of individual differences, probably brought on by an increase in
      personal freedom and a reduction in social constraints. Understanding the
      etiology of DA is likely to reveal key components, acting directly or indirectly,
      in the pathway(s) leading to drug initiation, abuse and dependence.

PMID- 17445285
TI  - The ecological validity of neuropsychological assessment and the role of
      depressive symptoms in moderate to severe traumatic brain injury.
AB  - Evaluating the ecological validity of neuropsychological tests has become an
      increasingly important topic. Previous research suggests that neuropsychological
      tests have a moderate level of ecological validity when predicting everyday
      functioning. The presence of depressive symptoms, however, may impact the
      relationship between neuropsychological tests and real world performance. The
      current study empirically tests this hypothesis in a sample of 216 participants
      with moderate to severe traumatic brain injury (TBI) who completed
      neuropsychological testing, self-report of mood symptoms, and report of everyday
      functioning six months post-injury. Contrary to some previous research and
      clinical lore, results indicated that depression was weakly related to
      neuropsychological test performance, although it was more strongly related to
      everyday functioning. Neuropsychological test performance was also significantly
      related to everyday functioning. The ecological validity of the
      neuropsychological tests together was not impacted by depressive symptoms, when
      predicting significant other ratings of functional status. However, patient self
      report seems somewhat less related to neuropsychological performance in those
      with significant depressive symptoms. Neuropsychological test performance was
      equally related to self and other report of everyday functioning in patients
      without significant depressive symptoms.

PMID- 17445286
TI  - Magnetic resonance imaging correlates of set shifting.
AB  - The purpose of this study was to examine the relationships between lobar volumes
      and set shifting. We studied 101 subjects, including 36 normal controls, 16
      patients with probable Alzheimer's disease, 30 patients with frontotemporal
      dementia (FTD), and 19 patients with semantic dementia (SD), using a shifting
      paradigm that carefully controlled for component abilities. Subjects were
      administered two conditions of the Delis-Kaplan Executive Function System (D
      KEFS) Design Fluency Test. In the control condition (DF:Control), examinees
      generated as many unique designs as possible in 60 s by drawing lines connecting
      only unfilled dots. In the switching condition (DF:Switch), examinees generated
      designs by drawing lines alternating between filled and unfilled dots. We used
      BRAINS2 software to generate volumes of the right and left frontal, temporal, and
      parietal lobes. Partial correlations and multiple regressions showed that, after
      controlling for Mini-Mental State Examination and DF:Control, only the right and
      left frontal lobe volumes significantly correlated with the DF:Switch, most
      clearly in the FTD and SD groups. Follow-up analyses indicated that frontal
      contributions to shifting were not related to working memory. Results highlight
      the importance of carefully controlling for component cognitive processes when
      studying executive functioning.

PMID- 17445287
TI  - Influence of major antiepileptic drugs on neuropsychological function: results
      from a randomized, double-blind, placebo-controlled withdrawal study of seizure
      free epilepsy patients on monotherapy.
AB  - The aim of this study was to assess cognitive effects of anticonvulsants in a way
      that would yield results that are most directly applicable to epilepsy
      populations. This was done with a placebo-controlled, prospective, randomized,
      double-blind, parallel group study of anticonvulsant withdrawal in a population
      of subjects taking a single anticonvulsant with completely controlled seizures.
      Outcomes of this study on cognitive measures from the California Computerized
      Assessment Package have recently been reported. To aid comparison with results of
      prior studies, we report outcomes here on several more standard measures of
      neuropsychological function. The major findings were that, in subjects with
      therapeutic drug levels at baseline, drug withdrawal was associated with
      significant improvement in performance on the Controlled Oral Word Association
      Test and the Stroop Color-Word Interference Test. Comparable results were
      achieved in the subgroup taking carbamazepine.

PMID- 17445288
TI  - A predominance of category deficits for living things in Alzheimer's disease and
      Lewy body dementia.
AB  - Although semantic memory impairment is well documented in patients with dementia
      of the Alzheimer's type, questions remain as to whether the deficit extends to
      other forms of dementia and whether it differentially affects different domains
      of knowledge. We examined category naming on two tasks (picture naming and naming
      to-description) in patients with Alzheimer's disease (AD: n = 11), Lewy body
      dementia (DLB: n = 11) and healthy elderly matched controls (n = 22). The DLB and
      AD groups showed significantly worse naming on both tasks, although the AD
      patients were more impaired than the DLB patients. Like some AD patients, some
      DLB patients showed evidence of category-specific naming deficits, and
      strikingly, all 25 significant category dissociations were for living things. The
      latter finding accords with the preponderance of living deficits previously
      documented for AD patients, but extends this finding to DLB patients. The
      implications of this category bias is discussed in relation to relevant models of
      category specificity.

PMID- 17445289
TI  - Prospective memory in multiple sclerosis.
AB  - There is considerable evidence that multiple sclerosis (MS) is associated with
      impaired retrospective memory. However, although preliminary evidence suggests
      that prospective memory is also affected by the disorder, the degree and nature
      of the impairment remains to be clarified. Twenty participants with MS were
      compared with 20 matched controls on Virtual Week, a measure of prospective
      memory that closely represents the types of prospective memory tasks that
      actually occur in everyday life, and provides an opportunity to investigate the
      different sorts of prospective memory failures that occur. The results indicated
      that irrespective of the specific prospective memory task demands, MS
      participants' performance was significantly impaired relative to controls. MS
      deficits could not be attributed to problems with retrospective memory because MS
      participants in the present study did not differ significantly from controls on
      measures of long- and short-term memory, and significant impairment was observed
      on a prospective memory task, which imposed only minimal demands on retrospective
      memory. These results therefore suggest that individuals with MS may experience
      general difficulties with prospective memory. The practical and theoretical
      implications of these findings are discussed.

PMID- 17445290
TI  - Information processing deficits in multiple sclerosis: a matter of complexity.
AB  - This study examined the relationship between processing speed (PS) and working
      memory (WM), as measured by performance on an n-back task, in relapsing-remitting
      multiple sclerosis (RRMS) patients. Simple PS was defined as reaction time (RT)
      on the 0-back task and complex PS was defined as RT on both the 1-back and 2-back
      tasks. Participants were administered all three n-back tasks (0-, 1-, and 2
      back). Total correct responses, total dyads, and RTs were recorded. As expected,
      RT for all participants slowed as WM load increased. MS patients had slower RTs
      than controls across all tasks, and the difference between groups for RT was
      greatest during the 2-back task. When RT for simple PS (0-back) was parsed from
      the 1- and 2-back tasks, MS patients still showed impaired complex PS compared to
      controls. MS patients also made significantly fewer total correct responses and
      had fewer dyads than controls only on the 2-back task. These findings suggest
      that both WM and PS deficits are present in RRMS, and that as WM demand increases
      (from 1- to 2-back) both PS and WM deficits become more prominent.

PMID- 17445291
TI  - How does the homophone meaning generation test associate with the phonemic and
      semantic fluency tests? A quantitative and qualitative analysis.
AB  - The current study examines whether the Homophone Meaning Generation Test (HMGT;
      Warrington, 2000) is correlated with the phonemic and/or the semantic fluency
      tests and compares its association with the number of switches and clusters and
      the mean cluster size of these two tasks. One hundred healthy Hebrew speakers (18
      35 years of age; mean = 24.9) generated meanings for 24 homophones and provided
      words beginning in three different letters, as well as words belonging to three
      semantic categories. Results show that the HMGT score correlated significantly
      and similarly with the total score of both the phonemic and the semantic fluency
      tests. There was a significant correlation between the HMGT and the number of
      phonemic switches and clusters, but not between the HMGT and the mean phonemic
      cluster size. The HMGT correlated with the number of semantic switches and
      clusters, as well as with the mean semantic cluster size. The findings suggest
      that the relationship between these tests is mediated by a shared executive
      component, attesting to the HMGT's utility in tapping into mechanisms of shifting
      and mental flexibility.

PMID- 17445292
TI  - Linguistic changes in verbal expression: a preclinical marker of Alzheimer's
      disease.
AB  - Despite the many studies examining linguistic deterioration in Alzheimer's
      disease (AD), very little is known about changes in verbal expression during the
      preclinical phase of this disease. The objective of this study was to determine
      whether changes in verbal expression occur in the preclinical phase of AD. The
      sample consisted of 40 healthy Spanish speakers from Antioquia, Colombia. A total
      of 19 were carriers of the E280A mutation in the Presenilin 1 gene, and 21 were
      noncarrier family members. The two groups were similar in age and education. All
      the participants were shown the Cookie Theft Picture Card from the Boston
      Diagnostic Aphasia Examination and were asked to describe the scene. Specific
      grammatical and semantic variables were evaluated. The performance of each group
      was compared using multivariate analyses of the variance for semantic and
      grammatical variables, and errors. Carriers of the mutation produced fewer
      semantic categories than noncarriers. In the preclinical phase of AD, changes in
      verbal expression are apparent and early detection of these differences may
      assist the early diagnosis of and intervention in this disease.

PMID- 17445293
TI  - Response validity in forensic neuropsychology: exploratory factor analytic
      evidence of distinct cognitive and psychological constructs.
AB  - Forensic neuropsychology studies usually address either cognitive effort or
      psychological response validity. Whether these are distinct constructs is
      unclear. In 122 participants evaluated in a compensation-seeking context, the
      present Exploratory Factor Analysis examined whether forced-choice cognitive
      effort measures (Victoria Symptom Validity Test, Test of Memory Malingering,
      Letter Memory Test) and Minnesota Multiphasic Personality Inventory, Second
      Edition (MMPI-2) validity scales (L, F, K, FBS, Fp, RBS, Md, Dsr2, S) load on
      independent factors. Regardless of factor rotation strategy (orthogonal or
      oblique), four response validity factors emerged by means of both Principal
      Components Analysis (82.7% total variance) and Principal-Axis Factor Analysis
      (74.1% total variance). The four factors were designated as follows: Factor I,
      with large loadings from L, K, and S--underreporting of psychological symptoms;
      Factor II, with large loadings from FBS, RBS, and Md-overreporting of neurotic
      symptoms; Factor III, with large loadings from VSVT, TOMM, and LMT--insufficient
      cognitive effort; and Factor IV, with the largest loadings from F, Fp, and Dsr2-
      overreporting of psychotic/rarely endorsed symptoms. Results reflect the
      heterogeneity of response validity in forensic samples referred for
      neuropsychological evaluation. Administration of both cognitive effort measures
      and psychological validity scales is imperative to accurate forensic
      neuropsychological assessment.

PMID- 17445294
TI  - Anosognosia in mild cognitive impairment: Relationship to activation of cortical
      midline structures involved in self-appraisal.
AB  - Awareness of cognitive dysfunction shown by individuals with Mild Cognitive
      Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is
      variable. Anosognosia, or unawareness of loss of function, is beginning to be
      recognized as an important clinical symptom of MCI. However, little is known
      about the brain substrates underlying this symptom. We hypothesized that MCI
      participants' activation of cortical midline structures (CMS) during self
      appraisal would covary with level of insight into cognitive difficulties (indexed
      by a discrepancy score between patient and informant ratings of cognitive decline
      in each MCI participant). To address this hypothesis, we first compared 16 MCI
      participants and 16 age-matched controls, examining brain regions showing
      conjoint or differential BOLD response during self-appraisal. Second, we used
      regression to investigate the relationship between awareness of deficit in MCI
      and BOLD activity during self-appraisal, controlling for extent of memory
      impairment. Between-group comparisons indicated that MCI participants show subtly
      attenuated CMS activity during self-appraisal. Regression analysis revealed a
      highly significant relationship between BOLD response during self-appraisal and
      self-awareness of deficit in MCI. This finding highlights the level of
      anosognosia in MCI as an important predictor of response to self-appraisal in
      cortical midline structures, brain regions vulnerable to changes in early AD.

PMID- 17445295
TI  - Education correction using years in school or reading grade-level equivalent?
      Comparing the accuracy of two methods in diagnosing HIV-associated neurocognitive
      impairment.
AB  - Neuropsychological tests generally require adjustments for years of education
      when determining the presence of neurocognitive impairment. However, evidence
      indicates that educational quality, as assessed with reading tests, may be a
      better reflection of educational attainment among African Americans. Thus,
      African Americans with poor educational quality may be incorrectly classified
      with neurocognitive impairment based on neuropsychological tests. We compared the
      accuracy of neuropsychological test scores standardized using reading grade
      equivalent versus years of education in predicting neurocognitive impairment
      among a sample of Whites and African-American adults who were HIV+. Participants
      were examined by a neurologist and classified with or without HIV-associated
      neurocognitive disorders according to accepted criteria. Participants were also
      classified as impaired versus not impaired based on their neuropsychological test
      scores standardized by 1) self-reported education or 2) WRAT-3 reading grade
      level. Cross tabulation tables were used to determine agreement of the two
      methods in detecting impairment. Among African-Americans, standardized scores
      derived from reading scores had greater specificity than those derived from years
      of education (84.1% vs. 77.3). Among the Whites, correction based on years of
      education had both greater specificity and sensitivity. The results suggest that
      reading tests may be a useful alternative for determining NCI among African
      Americans.

PMID- 17445296
TI  - Neuropsychological correlates of organic alexithymia.
AB  - Deficits in emotional recognition and perception following traumatic brain injury
      (TBI) have been associated with alexithymia (Henry et al., 2006; Williams et al.,
      2001). This study examined the prevalence of alexithymia in a TBI population, and
      its relationship to injury severity, neuropsychological ability and affective
      disorder. A total of 121 patients completed the Toronto Alexithymia Scale-20 (TAS
      20), a measure that addresses 3 distinct characteristics of the alexithymia
      concept; difficulty identifying feelings, difficulty describing feelings, and
      externally oriented thinking. Patients also completed a neuropsychological
      assessment and measures of depression and anxiety. Results confirm a high
      prevalence of alexithymia after TBI, relative to the general population and an
      orthopedic control group. There was no relationship between injury severity and
      the presence of alexithymia. A negative relationship was found between
      alexithymia and verbal and sequencing abilities, but there was no relationship
      with executive dysfunction or any other cognitive domain. Moderate correlations
      were obtained between alexithymia and affective disorder; regression analyses
      indicated that alexithymia, depression, and anxiety should be considered
      distinct, but overlapping constructs. The results of this study suggest that
      increased neuropsychological attention should be directed towards emotional
      change after head injury and its relationship with cognition and psychosocial
      outcome.

PMID- 17445297
TI  - Older adults make less advantageous decisions than younger adults: cognitive and
      psychological correlates.
AB  - This study tested the hypotheses that older adults make less advantageous
      decisions than younger adults on the Iowa Gambling Task (IGT). Less advantageous
      decisions, as measured by the IGT, are characterized by choices that favor larger
      versus smaller immediate rewards, even though such choices may result in long
      term negative consequences. The IGT and measures of neuropsychological function,
      personality, and psychopathology were administered to 164 healthy adults 18-85
      years of age. Older adults performed less advantageously on the IGT compared with
      younger adults. Additionally, a greater number of older adults' IGT performances
      was classified as "impaired" when compared with those of younger adults. Less
      advantageous decisions were associated with obsessive symptoms in older adults
      and with antisocial symptoms in younger adults. Performance on the IGT was
      positively associated with auditory working memory and psychomotor function in
      young adults, and in immediate memory in older adults.

PMID- 17445298
TI  - Substantial risk of "Accidental MCI" in healthy older adults: base rates of low
      memory scores in neuropsychological assessment.
AB  - When assessing older adults for mild cognitive impairment (MCI) or dementia, it
      is important to understand how often low memory scores are obtained in healthy
      people in order to minimize false positive diagnoses. This study examines the
      base rates of low memory scores in older adults across a battery of memory tests.
      Participants included older adults (55-79 years; N = 742) from the
      Neuropsychological Assessment Battery (NAB; Stern and White, 2003a)
      standardization sample. The NAB Memory Module consists of four co-normed memory
      tests (i.e., List Learning, Shape Learning, Story Learning, and Daily Living
      Memory) yielding 10 demographically corrected T-scores. When all 10 T-scores were
      examined simultaneously, 55.5% of older adults had one or more scores one
      standard deviation (SD) below the mean. At <1.5 SDs, 30.8% of healthy older
      adults obtained one or more low memory scores. Obtaining low memory scores occurs
      more often with lesser intellectual abilities. For example, 56.5% of older adults
      with low average intellectual abilities obtained one or more low memory scores
      (<1.5 SDs) compared to 21.1% with high average intellectual abilities.
      Understanding the base rates of low scores can reduce over-interpretation of
      isolated low memory scores and minimize false positive diagnoses of MCI.

PMID- 17445299
TI  - Language localization, the developing brain and childhood epilepsy: back to the
      future.
AB  - The defining role of language for communicating and forming social bonds has
      captured the imagination of scientists and scholars throughout the ages, and
      scientific inquiry into the neural correlates of language is now centuries old.
      Theories of linguistic structure and function occupy center stage in fields as
      diverse as neuroscience, embryology, anthropology and evolution. This should come
      as no surprise as the neural basis of linguistic function holds promise for
      understanding how the mind works and what makes us uniquely human.

PMID- 17445300
TI  - Intrahemispheric reorganization of language in children with medically
      intractable epilepsy of the left hemisphere.
AB  - We investigated language representation in nine children (six male, three female;
      5.6-17.7 years of age) who underwent surgical treatment of medically intractable
      epilepsy of the left hemisphere. Although interhemispheric reorganization has
      been previously documented in similar groups, this is the first study to
      systematically evaluate possible intrahemispheric effects of early insult. All
      cases had left hemisphere seizure foci and underwent extraoperative stimulation
      mapping (ESM) for language localization prior to receiving cortical resections.
      To compare ESM findings across subjects and to assess intrahemispheric
      reorganization, we developed a novel coregistration technique whereby independent
      raters plotted two-dimensional (2D) ESM findings in 3D standard space. Expressive
      language sites identified with ESM were compared with a structural probability
      map of pars opercularis, or Broca's area. The average difference between
      independent raters' estimates of 28 language sites was 3.9 mm (SD = 2.0),
      indicating excellent agreement; the coregistration procedure permitted assessment
      of 2D ESM findings in 3D standard space. We observed language sites in regions
      substantially anterior and superior to canonical Broca's area, possibly
      reflecting intrahemispheric reorganization. Findings suggest that left hemisphere
      insult in young children may result in anterior displacement of language within
      the frontal cortex.

PMID- 17445301
TI  - Measurement of cerebral perfusion with arterial spin labeling: Part 1. Methods.
AB  - Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) method that
      provides a highly repeatable quantitative measure of cerebral blood flow (CBF).
      As compared to the more commonly used blood oxygenation level dependent (BOLD)
      contrast-based methods, ASL techniques measure a more biologically specific
      correlate of neural activity, with the potential for more accurate estimation of
      the location and magnitude of neural function. Recent advances in acquisition and
      analysis methods have improved the somewhat limited sensitivity of ASL to
      perfusion changes associated with neural activity. In addition, ASL perfusion
      measures are insensitive to the low-frequency fluctuations commonly observed in
      BOLD experiments and can make use of imaging sequences that are less sensitive
      than BOLD contrast to signal loss caused by magnetic susceptibility effects. ASL
      measures of perfusion can aid in the interpretation of the BOLD signal change
      and, when combined with BOLD, can measure the change in oxygen utilization
      accompanying changes in behavioral state. Whether used alone to probe neural
      activity or in combination with BOLD techniques, ASL methods are contributing to
      the field's understanding of healthy and disordered brain function.

PMID- 17445303
TI  - Motor timing variability increases in preclinical Huntington's disease patients
      as estimated onset of motor symptoms approaches.
AB  - Huntington's disease (HD) is a neurodegenerative disorder diagnosed clinically
      with the development of choreiform movements. However, neuropsychological studies
      have demonstrated cognitive and psychiatric changes during the preclinical phase
      (pre-HD) prior to formal diagnosis. Previous studies have demonstrated the
      sensitivity of time reproduction tasks to basal ganglia pathology, as seen in
      clinical HD and Parkinson's disease. In this study, 29 pre-HD participants,
      ranging from 3 to 39 years from estimated onset (YEO) of HD based on genetic
      testing and chronological age, were administered the paced finger-tapping task
      using target intervals of 600 and 1200 ms. Mean inter-response interval, a
      measure of timing accuracy, did not systematically deviate from the target
      interval as a function of YEO. In contrast, timing variability increased
      curvilinearly as a function of YEO, but not with chronological age alone. Motor
      timing variability, but not accuracy, may serve as a marker to define the
      earliest behavioral changes in HD. The present study is among the first to
      examine the relationship between behavioral measures and YEO in pre-HD.

PMID- 17445302
TI  - Measurement of cerebral perfusion with arterial spin labeling: Part 2.
      Applications.
AB  - Arterial spin labeling (ASL) uses magnetic resonance imaging methods to measure
      cerebral blood flow (CBF) non-invasively. ASL CBF validly localizes brain
      function and may be especially useful for studies where the time frame of
      behavioral change is more than a few minutes, such as in longitudinal and
      treatment studies. ASL measures of cerebral perfusion are highly accurate in
      detecting lesion laterality in temporal lobe epilepsy, stenotic-occlusive
      disease, and brain tumors. Among lesioned patients, ASL CBF has excellent
      concurrent validity when correlated with CBF measured by Positron Emission
      Tomography or with dynamic susceptibility-weighted magnetic resonance. ASL CBF
      can predict tumor grading in vivo and can predict six-month response to the
      surgical treatment of brain tumors. ASL's capability to selectively and non
      invasively tag flow in major vessels may refine the monitoring of treatment of
      cerebrovascular disease and brain tumors. Conclusions about the utility of ASL
      are limited by the small sample sizes of the studies currently in the literature
      and by the uncertainty caused by the effect of brain disease on transit times of
      the magnetic tag. As the method evolves, ASL techniques will likely become more
      widely used in clinical research and practice.

PMID- 17445304
TI  - Mild visual acuity disturbances are associated with performance on tests of
      complex visual attention in MS.
AB  - Because MS patients frequently report visual acuity disturbances,
      neuropsychologists often screen patients for severe visual acuity disturbances
      and tailor test batteries that minimize the need for intact vision. Less is known
      about how mild visual acuity disturbances may influence neuropsychological test
      performance. This study examined the extent to which mild visual acuity
      disturbances influence performance on visually-based tests of complex attention.
      Relapsing-remitting and secondary progressive MS patients who reported adequate
      vision were recruited for this study. A battery was administered that included
      the oral version of the Symbol Digit Modalities Test (SDMT), the Visual Elevator
      (VE) subtest from the Test of Everyday Attention, and a reduced near vision eye
      chart. Results suggested that, in addition to measuring higher order cognitive
      processes, visual tests of attention are sensitive to mild primary visual
      disturbances in MS.

PMID- 17445305
TI  - Relationship between psychiatric status and frontal-subcortical systems in HIV
      infected individuals.
AB  - Human immunodeficiency virus (HIV)-infected adults frequently evidence both
      neurocognitive and psychiatric dysfunction. It was hypothesized that apathy and
      irritability, but not anxiety and depression, are related to HIV effects on
      frontal-subcortical systems. This hypothesis was evaluated by determining the
      degree to which these psychiatric features are associated with neurocognitive
      functioning that is dependent upon frontal-subcortical circuitry and, therefore,
      thought to be sensitive to the central nervous system effects of HIV. Rating
      scales assessing irritability, apathy, depression, and anxiety and a dual-task
      paradigm were administered to 189 HIV-seropositive (HIV+) and 53 HIV-seronegative
      participants. Deficits in dual-task performance and greater anxiety, depression,
      apathy, and irritability were observed in HIV+ participants. Simultaneous
      multivariate regression and communality analyses revealed that only apathy and
      irritability were associated with dual-task performance in HIV+ participants.
      Thus, these findings suggest that apathy and irritability, but not depression and
      anxiety, are likely associated with the effects of HIV on frontal-subcortical
      circuitry.

PMID- 17445306
TI  - Is bacterial colonisation of the tonsillar fossa a factor in post-tonsillectomy
      haemorrhage?
AB  - OBJECTIVES: To identify if there is a link between bacterial colonisation of the
      tonsillar fossa and post-tonsillectomy haemorrhage. STUDY DESIGN AND SETTING:
      Prospective non-interventional study of 105 patients who underwent tonsillectomy
      during a seven-month period. The study took place in a secondary care centre, the
      West Middlesex University Hospital. PARTICIPANTS: The participants were 105
      patients who consecutively underwent tonsillectomy. The exclusion criteria were
      any patients with suspected or known malignancy, or known bleeding dyscrasias.
      The participants underwent microbiological sampling of the tonsil pre
      operatively. MAIN OUTCOMES MEASURES: The outcome measures were primary or
      secondary bleeding, defined as any evidence of haemorrhage in the tonsillar
      fossae. RESULTS: Twenty-four per cent of patients undergoing tonsillectomy had
      positive cultures from their tonsils pre-operatively. Patients with bacterial
      colonisation of the tonsillar fossa pre-operatively had an increased rate of post
      tonsillectomy haemorrhage (odds ratio: 3.8, 1.1-12.1, 95 per cent confidence
      intervals, p = 0.04). CONCLUSION: This prospective study has found a relationship
      between bacterial colonisation of the tonsillar fossa and post-tonsillectomy
      haemorrhage. This suggests that there may be an argument for the use of
      antibiotics in those cases with positive pre-operative cultures. In view of the
      types of pathogens isolated, we feel that the management of a post-tonsillectomy
      bleed should include a beta lactamase inhibiting antibiotic.

PMID- 17445307
TI  - Epstein-Barr virus-associated smooth muscle tumour mimicking bilateral vocal
      process granuloma.
AB  - A case is presented of a 36-year-old Chinese woman with a renal transplant for
      end-stage renal failure due to Goodpasture's syndrome. She presented with a
      year's history of throat discomfort and acid regurgitation into her throat.
      Videolaryngoscopy revealed bilateral vocal process granuloma, presumed to be due
      to gastroesophageal reflux. A four-week course of high dose omeprazole was
      prescribed. On follow up a month later, the granulomas had enlarged, and laser
      excision was undertaken. Histological and immunohistochemical staining was
      consistent with Epstein-Barr virus-associated smooth muscle tumour. This is
      believed to be the first reported case in the English literature of such a tumour
      affecting the vocal process. The aim of this paper is to present the
      pathogenesis, clinical behaviour and treatment of Epstein-Barr virus-associated
      smooth muscle tumour, and to review the literature concerning the differential
      diagnosis of polypoid vocal process lesions.

PMID- 17445308
TI  - Recurrent facial paraesthesia secondary to maxillary antral cyst and dehiscent
      infraorbital canal: case report.
AB  - OBJECTIVES: To report a rare presentation of dehiscent infraorbital canal
      associated with a maxillary antral cyst. CASE REPORT: A 26-year-old woman
      presented with symptoms of right infraorbital nerve dysfunction experienced while
      travelling by aeroplane. She was subsequently diagnosed with dehiscent
      infraorbital canal and large maxillary antral cyst on computed tomography
      scanning. The cyst was removed by endoscopic sinus surgery, and the patient's
      symptoms resolved. DISCUSSION: The effects of barotrauma on the ears and
      paranasal sinuses are reviewed. This is the first report of infraorbital nerve
      dysfunction caused by altered atmospheric pressure in the presence of dehiscent
      infraorbital canal and maxillary antral cyst. Endoscopic sinus surgery was
      successful in relieving the symptoms in this case.

PMID- 17445309
TI  - Preliminary report of associated factors in wound infection after major head and
      neck neoplasm operations--does the duration of prophylactic antibiotic matter?
AB  - The aim of this study was to investigate whether an extended course of
      prophylactic antibiotic could reduce the wound infection rate in a subtropical
      country. Fifty-three consecutive cases scheduled to receive major head and neck
      operations were randomised into one-day or three-day prophylactic antibiotic
      groups. Thirteen cases (24.5 per cent) developed wound infections after
      operations. The duration of prophylactic antibiotic was not related to the
      surgical wound infection. However, pre-operative haemoglobulin less than 10.5
      g/dl (odds ratio: 7.24, 95 per cent confidence interval: 1.28-41.0) and
      reconstruction with a free flap or pectoris major myocutaneous flap during the
      operation (odds ratio: 11.04, 95 per cent confidence interval: 1.17-104.7) were
      associated factors significantly influencing post-operative wound infection.
      Therefore, one day of prophylactic antibiotic was effective in major head and
      neck procedures but should not be substituted for proper aseptic and meticulous
      surgical techniques.

PMID- 17445310
TI  - Otorhinolaryngologists' interest in facial plastic surgery: a survey in the
      United Kingdom and Ireland.
AB  - INTRODUCTION: Within the field of otorhinolaryngology, interest in facial plastic
      surgery has grown significantly in recent years. There is a lack of evidence in
      the literature documenting this interest in the British Isles. MATERIALS AND
      METHODS: 572 questionnaires were mailed to all members of the British Association
      of Otolaryngologists, Head and Neck Surgeons and to members of the Irish
      Otolaryngological Society. RESULTS: Our response rate was 68 per cent. One-third
      of respondents were performing facial plastic procedures regularly, most commonly
      otoplasty (80 per cent), rhinoplasty (74 per cent) and facial flaps (28 per
      cent). Two-thirds of respondents had attended supplementary courses in facial
      plastic surgery, and 65 per cent would like facial plastic surgery to compose one
      third of their daily practice. DISCUSSION: Facial plastic surgery has become a
      significant part of the otorhinolaryngologists' practice. They are now offering a
      wider variety of procedures in the area. This is the first paper to document this
      interest in the United Kingdom and Ireland.

PMID- 17445311
TI  - Analyses of the 1957 (Asian) influenza pandemic in the United Kingdom and the
      impact of school closures.
AB  - Many countries plan to close schools during a future influenza pandemic, although
      the potential impact is poorly understood. We apply a model of the transmission
      dynamics of pandemic influenza to consultation, serological and clinical data
      from the United Kingdom from the 1957 (Asian) influenza pandemic, to estimate the
      basic reproduction number (R0), the proportion of infected individuals who
      experience clinical symptoms and the impact of school/nursery closures. The R0
      for Asian influenza was about 1.8 and 60-65% of infected individuals were
      estimated to have experienced clinical symptoms. During a future pandemic,
      closure of schools/nurseries could reduce the epidemic size only by a very small
      amount (<10%) if R0 is high (e.g. 2.5 or 3.5), and modest reductions, e.g. 22%
      might be possible if it is low (1.8) and schools are closed early, depending on
      assumptions about contact patterns. Further data on contact patterns and their
      dependence on school closures are needed.

PMID- 17445312
TI  - Prevalence and determinants of high-risk human papillomavirus (HPV) infection and
      cervical cytological abnormalities in imprisoned women.
AB  - The aim of the study was to estimate the prevalence and risk factors associated
      with infection by high-risk human papillomavirus (HR-HPV) in cervix and squamous
      intra-epithelial lesions (SIL) in imprisoned women. This was done by a cross
      sectional study of imprisoned women attending the gynaecological clinic in
      Foncalent prison in Alicante, Spain. The study period was from May 2003 to
      December 2005. HR-HPV infection was determined through Digene HPV Test, Hybrid
      Capture II (HC-II). HPV typing was determined by multiplex nested PCR assay
      combining degenerate E6/E7 consensus primers. Multiple logistic regression
      modelling was used for the analysis of associations between variables where some
      were considered possible confounders after checking for interactions. A total of
      219 women were studied. HR-HPV prevalence was 27.4% and prevalence of SIL was
      13.3%. HIV prevalence was 18%, higher in Spaniards than in migrant women (24.6%
      vs. 14.3%, P<0.05). In multivariate analyses, risk factors for HPV infection were
      younger age (P for trend=0.001) and tobacco use (OR 2.62, 95% CI 1.01-6.73). HPV
      infection (OR 4.8, 95% CI 1.7-13.8) and HIV infection were associated with SIL
      (OR 4.8, 95% CI 1.6-14.1). The commonest HPV types were HPV16 (29.4%), HPV18
      (17.6%), HPV39 (17.6%) and HPV68 (17.6%). The prevalence of both HR-HPV infection
      and SIL in imprisoned women found in this study is high. Determinants for each of
      the outcomes studied were different. HPV infection is the most important
      determinant for SIL. A strong effect of HIV co-infection on the prevalence of SIL
      has been detected. Our findings reinforce the need to support gynaecological
      clinics in the prison setting.

PMID- 17445313
TI  - A mathematical model of the dynamics of Salmonella Cerro infection in a US dairy
      herd.
AB  - We developed a mathematical model of the transmission dynamics of salmonella to
      describe an outbreak of S. Cerro infection that occurred in a Pennsylvania dairy
      herd. The data were collected as part of a cooperative research project between
      the Regional Dairy Quality Management Alliance and the Agricultural Research
      Service. After the initial detection of a high prevalence of S. Cerro infection
      in the herd, a frequent and intensive sampling was conducted and the outbreak was
      followed for 1 year. The data showed a persistent presence of S. Cerro with a
      high prevalence of infection in the herd. The dynamics of host and pathogen were
      modelled using a set of nonlinear differential equations. A more realistically
      distributed (gamma-distributed) infectious period using multiple stages of
      infection was considered. The basic reproduction number was calculated and
      relevance to the intervention strategies is discussed.

PMID- 17445314
TI  - Uptake of pneumococcal polysaccharide vaccine in at-risk populations in England
      and Wales 1999-2005.
AB  - The UK has had a pneumococcal polysaccharide vaccination (PPV) programme for
      groups at higher risk of invasive disease since 1992. This paper presents data
      from a sample of primary-care practices (Q-RESEARCH) of PPV uptake in patients
      according to their risk status. Of 2.9 million registered patients in 2005, 2.1%
      were vaccinated with PPV in the preceding 12 months and 6.5% in the preceding 5
      years. Twenty-nine per cent of the registered population fell into one or more
      risk groups. The proportion of each risk group vaccinated in the previous 5 years
      ranged from 69% (cochlear implants), 53.4% (splenic dysfunction), 36.5% (chronic
      heart disease), 34.7% (diabetes), 22.9% (immunosuppressed), 28.7% (chronic renal
      disease), 15.9% (sickle cell disease) to 12.6% (chronic respiratory disease).
      Uptake was lower in areas where the non-white proportion of population was >10%.
      In conclusion, there remain large gaps in the uptake of PPV in several high-risk
      populations in the United Kingdom. Effective strategies need to be developed to
      address these deficiencies.

PMID- 17445315
TI  - Use of sensitivity analysis to assess the effects on anti-hepatitis A virus
      antibodies of access to household water supply.
AB  - The objective of this study was to assess the impact of a possible unmeasured
      confounding variable in a previously published association between the effects of
      household water supply and positive results for hepatitis A serology. This was
      estimated using a path of integration between two methods of sensitivity
      analysis, called Rosenbaum's method and Greenland's external adjustment. The
      association between household water supply and positive results for hepatitis A
      (outcome) serology was insensitive to confounding unless the odds ratio for the
      association between the confounder and the outcome was > or = 4. The integration
      of the two sensitivity analysis methods presented proved useful when assessing
      the effects of a potential unmeasured confounder.

PMID- 17445317
TI  - The seroepidemiology of varicella zoster virus among pregnant Bangladeshi and
      white British women in the London Borough of Tower Hamlets, UK.
AB  - We investigated the comparative seroepidemiology of varicella zoster virus (VZV)
      in pregnant women of two ethnic groups, white British and Bangladeshi, living in
      an inner city area of London, United Kingdom. Women aged 16-45 years were
      recruited from antenatal clinics of the Royal London Hospital in the Borough of
      Tower Hamlets. Complete data were obtained from 275 white British and 765
      Bangladeshi women. VZV antibody prevalence was 93.1% (95% CI 89.4-95.8) and 86.0%
      (95% CI 83.3-88.4) respectively. Women who were born in Bangladesh and lived
      there at least until the age of 15 years had the lowest odds of being immune (OR
      0.37, 95% CI 0.22-0.63). This implies they will have an increased risk of
      varicella during pregnancy. Women arriving in the United Kingdom in adulthood
      should be screened routinely during pregnancy and vaccination offered postpartum
      if they are susceptible.

PMID- 17445316
TI  - Epidemiological evidence for Mycobacterium avium subspecies paratuberculosis as a
      cause of Crohn's disease.
AB  - Mycobacterium avium subspecies paratuberculosis is the causative agent of Johne's
      disease, a chronic enteritis in ruminants including cattle, sheep, goats, and
      farmed deer. Recently, this bacterium has received an increasingly wide interest
      because of a rapidly growing body of scientific evidence which suggests that
      human infection with this microorganism may be causing some, and possibly all,
      cases of Crohn's disease. Recent studies have shown that a high percentage of
      people with Crohn's disease are infected with M. avium subsp. paratuberculosis;
      whether the association of this bacterium and Crohn's disease is causal or
      coincidental is not known. Crohn's disease is a gastrointestinal disease in
      humans with similar histopathological findings to those observed in the
      paucibacillary form of Johne's disease in cattle. The search for risk factors in
      Crohn's disease has been frustrating. However, epidemiologists have gathered
      enough information that points to an association between M. avium subsp.
      paratuberculosis and Crohn's disease. This paper reviews epidemiological models
      of disease causation, the major philosophical doctrines about causation, the
      established epidemiological criteria for causation, and the currently known
      epidemiological evidence of M. avium subsp. paratuberculosis as a possible cause
      of Crohn's disease.

PMID- 17445318
TI  - Necrotizing fasciitis in captive juvenile Crocodylus porosus caused by
      Streptococcus agalactiae: an outbreak and review of the animal and human
      literature.
AB  - We observed an outbreak of necrotizing fasciitis associated with Streptococcus
      agalactiae infection in a group of juvenile saltwater crocodiles (Crocodylus
      porosus). We undertook screening of crocodiles and the environment to clarify the
      source of the outbreak and evaluated the isolates cultured from post-mortem
      specimens with molecular methods to assess clonality and the presence of known
      group B streptococcal virulence determinants. The isolates were indistinguishable
      by pulsed-field gel electrophoresis. They were a typical serotype Ia strain with
      the Calpha-like protein gene, epsilon (or alp1), the mobile genetic elements
      IS381 ISSag1 and ISSag2, and belonged to multi-locus sequence type (ST) 23. All
      of these characteristics suggest they were probably of human origin. We review
      the medical and veterinary literature relating to S. agalactiae necrotizing
      fasciitis, epidemiology and virulence determinants.

PMID- 17445319
TI  - ICD-10 codes are a valid tool for identification of pneumonia in hospitalized
      patients aged > or = 65 years.
AB  - This study examines the validity of using ICD-10 codes to identify hospitalized
      pneumonia cases. Using a case-cohort design, subjects were randomly selected from
      monthly cohorts of patients aged > or = 65 years discharged from April 2000 to
      March 2002 from two large tertiary Australian hospitals. Cases had ICD-10-AM
      codes J10-J18 (pneumonia); the cohort sample was randomly selected from all
      discharges, frequency matched to cases by month. Codes were validated against
      three comparators: medical record notation of pneumonia, chest radiograph (CXR)
      report and both. Notation of pneumonia was determined for 5098/5101 eligible
      patients, and CXR reports reviewed for 3349/3464 (97%) patients with a CXR.
      Coding performed best against notation of pneumonia: kappa 0.95, sensitivity
      97.8% (95% CI 97.1-98.3), specificity 96.9% (95% CI 96.2-97.5), positive
      predictive value (PPV) 96.2% (95% CI 95.4-97.0) and negative predictive value
      (NPV) 98.2% (95% CI 97.6-98.6). When medical record notation of pneumonia is used
      as the standard, ICD-10 codes are a valid method for retrospective ascertainment
      of hospitalized pneumonia cases and appear superior to use of complexes of
      symptoms and signs, or radiology reports.

PMID- 17445321
TI  - Outbreak of waterborne cryptosporidiosis associated with low oocyst
      concentrations.
AB  - Water treatment plants in the United Kingdom at significant risk of
      cryptosporidiosis and using conventional filtration methods have been required to
      install 24-h monitoring systems since April 2000. No major waterborne outbreaks
      have been described since 2001. Small outbreaks have been associated with water.
      This paper describes such an outbreak. Data from a local multi-agency
      surveillance system was used to describe the outbreak, including mapping cases
      against water supply zones. A case-control study investigated hypotheses raised.
      All cases were genotype 1. Early cases were in the supply zone of a surface water
      treatment plant that had met treatment standards. Later cases included residents
      in a different supply zone that temporarily received water from the implicated
      plant. Cases reported more consumption of domestic mains water than controls.
      Descriptive and analytical epidemiology thus supported drinking water as a source
      of cryptosporidiosis from a plant meeting regulatory requirements. The evidence
      for setting drinking-water standards needs review.

PMID- 17445320
TI  - Emerging zoonoses and vector-borne infections affecting humans in Europe.
AB  - The purpose of this study was to assess and describe the current spectrum of
      emerging zoonoses between 2000 and 2006 in European countries. A computerized
      search of the Medline database from January 1966 to August 2006 for all zoonotic
      agents in European countries was performed using specific criteria for emergence.
      Fifteen pathogens were identified as emerging in Europe from 2000 to August 2006:
      Rickettsiae spp., Anaplasma phagocytophilum, Borrelia burgdorferi, Bartonella
      spp., Francisella tularensis, Crimean Congo Haemorrhagic Fever Virus, Hantavirus,
      Toscana virus, Tick-borne encephalitis virus group, West Nile virus, Sindbis
      virus, Highly Pathogenic Avian influenza, variant Creutzfeldt-Jakob disease,
      Trichinella spp., and Echinococus multilocularis. Main risk factors included
      climatic variations, certain human activities as well as movements of animals,
      people or goods. Multi-disciplinary preventive strategies addressing these
      pathogens are of public health importance. Uniform harmonized case definitions
      should be introduced throughout Europe as true prevalence and incidence estimates
      are otherwise impossible.

PMID- 17445322
TI  - An outbreak of Escherichia coli O157:H7 infection in southern Sweden associated
      with consumption of fermented sausage; aspects of sausage production that
      increase the risk of contamination.
AB  - A large outbreak of enterohaemorrhagic Escherichia coli (EHEC) infections
      occurred in southern Sweden during autumn 2002. A matched case-control study was
      performed and indicated an association between consumption of fermented sausage
      and EHEC infection (odds ratio 5.4, P<0.002). Pulsed-field gel electrophoresis
      analysis identified a strain of E. coli O157:H7 in clinical faecal isolates,
      which was identical to a strain isolated from sausage samples obtained from
      households of infected individuals. A combination of microbiological and
      epidemiological results established a link between sausage consumption and the
      outbreak in 30 out of a total of 39 investigated cases. Contaminated beef was
      suspected to be the source of infection. Delayed start of fermentation, lack of
      heat-treatment and a short curing period in cold temperature were identified as
      the main factors enabling EHEC survival. EHEC can survive throughout the entire
      production process of fermented sausage if curing conditions are inadequate.

PMID- 17445323
TI  - Identification and characterization of a putative agglutination/immobilization
      antigen on the surface of Cryptocaryon irritans.
AB  - The ciliated protozoan Cryptocaryon irritans, a parasite of seawater fishes, was
      found to express an antigen that elicits antibodies in rabbits and tiger puffer
      (Takifugu ruburipes). Serum from rabbits and fish immunized with theronts had
      agglutination/immobilization activity against theronts in vitro; fish serum
      antibody levels (measured by enzyme-linked immunosorbent assays: ELISA)
      correlated with this activity. Anti-theront antibody levels in fish were
      significantly higher in the immunized group as compared with control fish at 2
      weeks after booster immunization (injection of bovine serum albumin; Student's t
      test, P<0.01). Biochemical analyses indicated that a Triton X-114-soluble 32 kDa
      theront integral membrane protein may be the agglutination/immobilization
      antigen. Indirect immunofluorescence staining of theronts suggested that this 32
      kDa antigen was expressed on the surface of cilia. The full-length 32 kDa antigen
      cDNA contained 1147 basepairs, encoding a 328-amino acid protein including
      hydrophobic N- and C-termini. As with Tetrahymena and Paramecium spp., TAA and
      TAG appear to be used as glutamine codons in the 32 kDa antigen gene.

PMID- 17445324
TI  - Development and validation of flow cytometric measurement for parasitaemia using
      autofluorescence and YOYO-1 in rodent malaria.
AB  - An automated flow cytometric (FCM) detection method has been developed and
      validated with a simple diagnostic procedure in parasitized erythrocytes of
      Plasmodium berghei-infected rats using the nucleic acid-binding fluorescent dye
      YOYO-1. High levels of reticulocytes were detected during the course of the
      infection, ranging from 1.2-51.2%, but any RNA potentially confounding the assay
      could be removed by digestion with RNAse. The cell counts of uninfected,
      infected, and nucleated cells occurred with high precision. The cells were
      divided into different populations according to their physical or chemical
      properties but various factors within the assay such as cell fixation, RNA
      digestion, and compensation required optimization. In this study, FCM greatly
      simplified and accelerated parasite detection, with a mean precision of 4.4%,
      specificity of 98.9% and accuracy of 101.3%. The detection and quantitation
      limits in the assay were 0.024% and 0.074% parasitaemia, respectively. Overall,
      the parasite counts by FCM measurement correlated highly (r2=0.954-0.988) with
      the parasitaemia measured by light microscopical analysis when animals treated
      with suppressive, clearance, and curative doses of novel antimalarial drugs were
      examined. The lower levels of parasitaemia (30%) detected by microscopy compared
      to FCM may be related to a number of schizonts externally attached to the
      erythrocyte membranes that normally would not be included in microscopy counting.
      Lower sampling error and reliable identification of rodent erythrocyte parasites
      based on the principles of FCM have replaced the traditional blood smear in our
      laboratory.

PMID- 17445325
TI  - Antioxidant gene expression and function in in vitro-developing Schistosoma
      mansoni mother sporocysts: possible role in self-protection.
AB  - The ability of the larval forms of Schistosoma mansoni to invade and parasitize
      their molluscan host, Biomphalaria glabrata, is determined by a multitude of
      factors. In this study we sought to elucidate the possible mechanisms by which
      the invading larvae are able to counteract the potentially harmful oxidative
      environment presented by the host upon initial miracidial infection. This was
      attempted by examining the gene expression profile of parasite antioxidant
      enzymes of the linked glutathione-(GSH) thioredoxin (Trx) redox pathway during
      early intramolluscan larval development. Three such enzymes, the peroxiredoxins
      (Prx1, Prx2 and Prx3) were examined as to their activity and sites of expression
      within S. mansoni miracidia and in vitro-cultured mother sporocysts. Results of
      these studies demonstrated that the H(2)O(2)-reducing enzymes Prx1 and 2 are
      upregulated during early mother sporocyst development compared to miracidia.
      Immunolocalization studies further indicated that Prx1 and Prx2 proteins are
      expressed within the apical papillae of miracidia and tegumental syncytium of
      sporocysts, and are released with parasite excretory-secretory proteins (ESP)
      during in vitro larval transformation. Removal of Prx1 and Prx2 from larval ESP
      by immunoabsorption significantly reduced the ability of ESP to breakdown
      exogenous H(2)O(2), thereby directly linking ESP Prx proteins with H(2)O(2)
      scavenging activity. Moreover, exposure of live sporocysts to exogenous
      H(2)O(2)stimulated an upregulation of Prx1 and 2 gene expression suggesting the
      involvement of H(2)O(2)-responsive elements in regulating larval Prx gene
      expression. These data provide evidence that Prx1 and Prx2 may function in the
      protection of S. mansoni sporocysts during the early stages of infection.

PMID- 17445326
TI  - Poorer results of mice with latent toxoplasmosis in learning tests: impaired
      learning processes or the novelty discrimination mechanism?
AB  - The heteroxenous protozoan parasite Toxoplasma gondii is transmitted from the
      intermediate host (any warm-blooded animal) to the definitive host (members of
      the felidae) by carnivory. The infected intermediate hosts develop several
      specific behavioural changes that are usually considered products of manipulative
      activity of the parasite aimed to increase the probability of its transmission to
      the definitive host. Among other changes, the infected rodents were shown to have
      impaired learning capability. All previous studies were done 2-6 weeks after the
      infection. Therefore, it was difficult to resolve whether the observed impairment
      of learning processes was a result of acute or latent toxoplasmosis, i.e. whether
      it was a side-effect of the disease or a product of manipulation activity. Here
      we studied the learning capability of Toxoplasma-infected mice in the static rod
      test and 8-arm radial maze test and their spontaneous activity in the wheel
      running test 10 weeks after the infection. The infected mice achieved worse
      scores in the learning tests but showed higher spontaneous activity in the wheel
      running test. However, a detailed study of the obtained results as well as of the
      data reported by other authors suggested that the differences between infected
      and control mice were a result of impaired ability to recognize novel stimuli
      rather than of impaired learning capacity in animals with latent toxoplasmosis.

PMID- 17445327
TI  - Local climate aridity influences the distribution of thelastomatoid nematodes of
      the Australian giant burrowing cockroach.
AB  - In this study, we examined the effects of local climate aridity on the richness
      and composition of the thelastomatoid (Nematoda: Oxyurida) guild parasitizing the
      Australian giant burrowing cockroach, Macropanesthia rhinoceros (Blattodea:
      Geoscapheinae). In total, 9 thelastomatoid species parasitized this cockroach in
      north-eastern Australia (Queensland). Local observed richness ranged from 3
      species (in Cooktown, Magnetic Island, Maiden Springs and Whitsunday Island) to 7
      species (in Rochford Scrub). The lowest richness occurred in both relatively wet
      and dry climates, and the highest richness was in moderate climates. Three
      species, Cordonicola gibsoni, Leidynemella fusiformis and Travassosinema
      jaidenae, were found at all 13 collection sites. One species, Geoscaphenema
      megaovum, was found exclusively in dry to moderate climates. The remaining
      species, Blattophila sphaerolaima, Coronostoma australiae, Desmicola ornata,
      Hammerschmidtiella hochi and Jaidenema rhinoceratum, were found in moderate
      climates only. We hypothesize that the egg is the stage in the thelastomatoid
      life-cycle most vulnerable to the effects of adverse climate and that the
      geographical distribution for each species is, in part, bound by environments
      that are too dry, resulting in egg desiccation, and by environments that are too
      wet, resulting in decreased oxygen uptake across the egg-shell and in osmotic
      lysing.

PMID- 17445328
TI  - Infection by a vertically-transmitted microsporidian parasite is associated with
      a female-biased sex ratio and survival advantage in the amphipod Gammarus
      roeseli.
AB  - SUMMARYVertically transmitted parasites may have positive, neutral or negative
      effects on host fitness, and are also predicted to exhibit sex-specific virulence
      to increase the proportion or fitness of the transmitting sex. We investigated
      these predictions in a study on the survival and sex ratio of offspring of the
      amphipod Gammarus roeseli from females infected by the vertically transmitted
      microsporidia Nosema granulosis. We found, to our knowledge, the first evidence
      for a positive relationship between N. granulosis infection and host survival.
      Infection was associated with sex ratio distortion, not by male-killing, but
      probably by parasite-induced feminization of putative G. roeseli males. This
      microsporidia also feminizes another amphipod host, Gammarus duebeni, which is
      phylogenetically and biogeographically distant from G. roeseli. Our study
      suggests that the reproductive system of gammarids is easily exploited by these
      vertically-transmitted parasites, although the effects of infections on host
      fitness may depend on specific host-parasite species interactions.

PMID- 17445329
TI  - Determinants of current contraceptive use and method choice in Mongolia.
AB  - This study examines the determinants of current contraceptive use and method
      choice in Mongolia using data from the 1998 Mongolian Reproductive Health Survey
      and 2000 Mongolian Population and Housing Census. Since 1976, access to modern
      contraceptives has been liberalized and all restrictions on the use, distribution
      and import of contraceptives were removed in 1989. There were some increases in
      the use of modern contraceptives among married women in the 1990s; however, at
      the start of the twenty-first century the IUD and periodic abstinence remain the
      most widely used methods. Women with higher levels of education are more likely
      to be current users of contraception, and if they are current users, they are
      more likely to choose the IUD and traditional methods. Women living in rural
      areas have a higher probability of using contraception and are more likely to
      choose the IUD and traditional methods. Significant variations exist between
      primary sampling units in current contraceptive use and in the choice of modern
      methods. Community-level variables were important predictors in reducing
      variation between primary sampling unit, when other modern methods were compared
      with traditional methods.

PMID- 17445330
TI  - Reaching providers is not enough to increase IUD use: a factorial experiment of
      'academic detailing' in Kenya.
AB  - Although the IUD is an extremely effective and low-cost contraceptive method, its
      use has declined sharply in Kenya in the past 20 years. A study tested the
      effectiveness of an outreach intervention to family planning providers and
      community-based distribution (CBD) agents in promoting use of the IUD in western
      Kenya. Forty-five public health clinics were randomized to receive the
      intervention for providers only, for CBD agents only, for both providers and CBD
      agents, or no detailing at all. The intervention is based on pharmaceutical
      companies' "detailing" models and included education/motivation visits to
      providers and CBD programmes, as well as provision of educational and promotional
      materials. District health supervisors were given updates on contraceptives,
      including the IUD, and were trained in communication and message development
      prior to making their detailing visits. Detailing only modestly increased the
      provision of IUDs, and only when both providers and CBD agents were targeted. The
      two detailing visits do not appear sufficient to sustain the effect of the
      intervention or to address poor provider attitudes and lack of technical skills.
      The cost per 3.5 years of pregnancy protection was US$49.57 for the detailing
      intervention including the cost of the IUD, compared with US$15.19 for the
      commodity costs of the current standard of care--provision of the injectable
      contraceptive depot-medroxyprogesterone acetate (DMPA). The effectiveness of
      provider-based activities is amplified when concurrent demand creation activities
      are carried out. However, the cost of the detailing in comparison to the small
      number of IUDs inserted indicates that this intervention is not cost-effective.

PMID- 17445331
TI  - A model to account for the consequences of host nutrition on the outcome of
      gastrointestinal parasitism in sheep: model evaluation.
AB  - This paper describes sensitivity analyses and expectations obtained from a
      mathematical model developed to account for the effects of host nutrition on the
      consequences of gastrointestinal parasitism in sheep. The scenarios explored
      included different levels of parasitic challenge at different planes of
      nutrition, for hosts differing only in their characteristics for growth. The
      model was able to predict the consequences of host nutrition on the outcome of
      parasitism, in terms of worm burden, number of eggs excreted per gram faeces and
      animal performance. The model outputs predict that conclusions on the ability of
      hosts of different characteristics for growth to cope with parasitism (i.e.
      resistance) depend on the plane of nutrition. Furthermore, differences in the
      growth rate of sheep, on their own, are not sufficient to account for differences
      in the observed resistance of animals. The model forms the basis for evaluating
      the consequences of differing management strategies and environments, such as
      breeding for certain traits associated with resistance and nutritional
      strategies, on the consequences of gastrointestinal parasitism on sheep.

PMID- 17445332
TI  - Density dependence of feeding success in haematophagous ectoparasites.
AB  - We studied the effect of density on feeding success of 2 fleas, Xenopsylla
      conformis and Xenopsylla ramesis, when exploiting rodents Meriones crassus and
      Gerbillus dasyurus. We tested 2 alternative hypotheses: (i) that intraspecific
      interference competition occurs and, thus, feeding success of a flea decreases
      with an increase in density and (ii) that facilitation via suppression of a host
      defence system occurs and thus, feeding success of a flea increases with an
      increase in density. The mean size of a bloodmeal and the proportion of highly
      engorged individuals in X. conformis feeding on both hosts were affected by
      density. When on G. dasyurus, both the size of a bloodmeal and the proportion of
      highly engorged individuals were lower at low (5-15 fleas per host) than at high
      (25-50 fleas per host) densities. The opposite was true when this flea fed on M.
      crassus. The mean bloodmeal size and proportions of highly engorged X. ramesis
      parasitizing either host were not affected by flea density. This study showed
      that the density dependence of feeding success of a flea (a) varied both between
      fleas and within-fleas between hosts and (b) indicated either intraspecific
      competition or facilitation via the host in a particular flea-host association.

PMID- 17445333
TI  - Comparative study of efficacy and toxicities of cisplatin vs vinorelbine as
      radiosensitisers in locally advanced head and neck cancer.
AB  - INTRODUCTION: Currently, concomitant chemoradiation using cisplatin is one of the
      standards of care for the management of head and neck cancer, but at the cost of
      increased acute toxicity. Our aim was to assess whether vinorelbine was less
      toxic and of at least comparable efficacy, if not better, compared with
      cisplatin. MATERIALS AND METHODS: A total of 72 patients with squamous cell
      carcinoma in the head and neck region were recruited, 40 in arm A and 32 in arm
      B. Patients in arm A received 40 mg/m2 cisplatin weekly. Patients in arm B
      received 6 mg/m2 vinorelbine weekly. Both arms also received 66 Gy of radiation
      in conventional fractionation. RESULTS AND ANALYSIS: There was no statistically
      significant difference in response rate or toxicities between the two arms,
      except for nausea and/or vomiting, which was significantly less frequent in the
      vinorelbine arm. CONCLUSION: Vinorelbine was as effective as cisplatin in
      controlling locoregional disease in locally advanced head and neck cancer, but
      was only marginally less toxic than cisplatin.

PMID- 17445334
TI  - Effectiveness of corticosteroids in otitis media with effusion: an experimental
      study.
AB  - OBJECTIVE: The aim of the present study was to investigate the dose-related
      effectiveness of corticosteroids in the management of otitis media with effusion,
      by using the objective assessment techniques of tympanometry and cytokine
      measurement. MATERIALS AND METHODS: The eustachian tubes of 42 male rats were
      obstructed. Thirty-six subjects with effusion were randomly divided into three
      equal groups: controls; 0.5 mg/kg/day corticosteroid; and 1 mg/kg/day
      corticosteroid. Concentrations of interleukin-1beta and tumour necrosis factor
      alpha in the middle-ear effusions were analysed using enzyme-linked immunosorbent
      assay. RESULTS: An effusion occurred on the 14th post-operative day and was
      present on the 30th post-operative day in the control group. Otomicroscopic
      examination and tympanometric measurement showed an improvement in the
      intervention groups. There was a significant difference between both intervention
      groups and the control group for both interleukin-1beta and tumour necrosis
      factor alpha concentrations (p 0.05). CONCLUSION: The study confirmed a short
      term beneficial effect of systemic steroids on resolution of otitis media with
      effusion in a rat model. Our results support the theory that corticosteroids
      significantly decrease concentrations of both interleukin-1beta and tumour
      necrosis factor alpha. In our model, the 0.5 mg/kg corticosteroid dose was as
      effective as the 1 mg/kg corticosteroid dose. Further studies should be carried
      out to determine the optimal dose and duration of corticosteroids in the
      treatment of otitis media with effusion.

PMID- 17445335
TI  - Variants of the CFC1 gene in patients with laterality defects associated with
      congenital cardiac disease.
AB  - OBJECTIVES: This study was designed to assess the frequency and types of genetic
      variants in CFC1 in children with laterality disorders associated with
      cardiovascular involvement. BACKGROUND: Laterality syndromes are estimated to
      comprise 3% of neonates with congenital cardiac disease. Genetic predisposition
      in some cases of laterality defects has been suggested by associated chromosomal
      anomalies and familial aggregation, often within consanguineous families,
      suggesting autosomal recessive inheritance. Mice with induced homozygous
      mutations in cfc1, and heterozygous CFC1 mutations in humans, have been
      associated with laterality defects. METHODS: Direct sequence analysis of the
      coding sequence of CFC1 was performed in 42 subjects with laterality defects and
      congenital cardiac disease. RESULTS: We identified 3 synonymous coding variants,
      3 non-synonymous coding variants (N21H, R47Q, and R78W), and 2 intronic variants
      in CFC1. The N21H variant was observed in 3 of 19 affected Caucasians, and the
      R47Q variant in another 2. Neither polymorphism was observed in Caucasian
      controls. Furthermore, all subjects with the N21H polymorphism had double outlet
      right ventricle. Transmission of both the N21H and R47Q polymorphisms from
      unaffected parents was demonstrated, and all three non-synonymous variants had
      significant allele frequencies in unaffected African-American subjects,
      suggesting that other factors must also contribute to laterality defects.
      CONCLUSIONS: Three non-synonymous variants in CFC1 were identified, the N21H
      variant being associated with laterality defects in Caucasians, but not fully
      penetrant. One or more of these non-synonymous missense variants may act as a
      susceptibility allele in conjunction with other genes, and/or environmental
      factors, to cause laterality defects.

PMID- 17445336
TI  - Transcatheter closure of coronary arterial fistulas using the new Amplatzer
      vascular plug.
AB  - We report our initial experience in using the Amplatzer vascular plug for closure
      of coronary arterial fistulas. The self-expanding, cylindrical, device is made
      from Nitinol wire mesh, and is available from 4 to 16 millimetres in diameter. We
      have now used the device to close fistulas in 3 patients, aged from 3 to 14
      years, who presented with ratios of pulmonary-to-systemic flow from 1.5 to 3. In
      2 patients, fistulas arising from the proximal right and left coronary arteries,
      with maximal diameters of 9 and 10 millimetres, respectively, had their narrowest
      diameter, of 6 millimetres, proximal to the entrance into the right atrium via a
      saccular aneurysm. The third fistula, with a maximal diameter of 16 millimetres,
      and with its origin from the circumflex coronary artery, entered the right atrium
      with nearly unrestricted flow, its narrowest diameter being 8 millimetres. For
      interventional closure, we chose plugs twice the diameter of the narrowest
      segment of the fistula, thus using 2 devices of 12 millimetres and one of 16
      millimetres diameter. An arteriovenous loop was established through the fistula
      by snaring an exchange guide wire. Using a 7 or 8 French guide catheter inserted
      through the femoral vein, all plugs were placed at the narrowest segment of the
      fistula, leading to immediate complete closure of 2 fistulas. The third patient,
      with a fistula of the circumflex coronary artery, who received the largest plug
      initially had residual flow, but the fistula was found to be completely occluded
      at 12 months follow-up examination. We have demonstrated, therefore, safe and
      effective usage of the new vascular plug for transcatheter closure of moderate-
      to large-sized coronary arterial fistulas. The plug offers an alternative to
      cardiac surgery, or occlusion using coils.

PMID- 17445337
TI  - Particle size of LDL is affected by the National Cholesterol Education Program
      (NCEP) step II diet in dyslipidaemic adolescents.
AB  - The objective was to determine the effects of the National Cholesterol Education
      Program (NCEP) step II diet on LDL and HDL particle size in dyslipidaemic
      adolescents. Forty-four dyslipidaemic adolescents, aged 10-18 years, participated
      in this case-control study. The control diet was a diet similar to what most
      Tehranian adolescents eat. NCEP step II diet was a diet with 30 % of energy as
      total fat, less than 7 % saturated fat, less than 200 mg cholesterol/d, less than
      15 % of energy as MUFA and less than 10 % as PUFA. Lipoprotein particle size was
      the major outcome variable, which was measured after 3 months of intervention.
      Comparison was made by the repeated measurement ANOVA. The mean BMI was 26.3 (sd
      4.2) kg/m2. There were no significant changes in weight or physical activity in
      the two groups during the study. The NCEP diet resulted in higher reduction in
      total cholesterol ( - 13 (sd 4) v. - 2 (sd 0.3) mg/dl, P < 0.001) and LDL ( - 9
      (sd 2) v. 3 (sd 0.6) mg/dl, P < 0.01), and higher increase in size of the LDL
      (1.7 (sd 0.4) v. 0.1 (sd 0.4) nanometer, P < 0.001). HDL particle size did not
      change significantly. NCEP step II diet had a favourable effect on the LDL
      particle size. The related mechanism needs to be studied in future experimental
      designs.

PMID- 17445338
TI  - Results of a screening programme to identify plants or plant extracts that
      inhibit ruminal protein degradation.
AB  - One aim of the EC Framework V project, 'Rumen-up' (QLK5-CT-2001-00 992), was to
      find plants or plant extracts that would inhibit the nutritionally wasteful
      degradation of protein in the rumen. A total of 500 samples were screened in
      vitro using 14C-labelled casein in a 30-min incubation with ruminal digesta.
      Eight were selected for further investigation using a batch fermentation system
      and soya protein and bovine serum albumin as proteolysis substrates; proteolysis
      was monitored over 12 h by the disappearance of soluble protein and the
      production of branched SCFA and NH3. Freeze-dried, ground foliage of Peltiphyllum
      peltatum, Helianthemum canum, Arbutus unedo, Arctostaphylos uva-ursi and Knautia
      arvensis inhibited proteolysis (P < 0.05), while Daucus carota, Clematis vitalba
      and Erica arborea had little effect. Inhibition by the first four samples
      appeared to be caused by the formation of insoluble tannin-protein complexes. The
      samples were rich in phenolics and inhibition was reversed by polyethyleneglycol.
      In contrast, K. arvensis contained low concentrations of phenolics and no
      tannins, had no effect in the 30-min assay, yet inhibited the degradation rate of
      soluble protein (by 14 %, P < 0.0001) and the production of branched SCFA (by 17
      %, P < 0.05) without precipitating protein in the 12-h batch fermentation. The
      effects showed some resemblance to those obtained in parallel incubations
      containing 3 mum-monensin, suggesting that K. arvensis may be a plant-derived
      feed additive that can suppress growth and activity of key proteolytic ruminal
      micro-organisms in a manner similar to that already well known for monensin.

PMID- 17445339
TI  - Fetal exposure to a maternal low-protein diet is associated with altered left
      ventricular pressure response to ischaemia-reperfusion injury.
AB  - Rats exposed to protein restriction as fetuses develop hypertension as adults.
      Hypertension increases the risk of myocardial ischaemia and infarction. We
      investigated whether rats exposed to low-protein diets in utero are more
      susceptible to myocardial ischaemia-reperfusion (IR) injury. Pregnant Wistar rats
      were fed control or low-protein (MLP) diets throughout pregnancy. At 4 and 8
      weeks postnatal age systolic blood pressure was determined in the offspring using
      tail-cuff plethysmography. At 6 months of age, rats were treated with saline or N
      acetylcysteine (NAC) for 48 h. Rapidly excised hearts were retro-perfused
      (Langendorff) to assess isolated cardiac function before (baseline), during 30
      min ischaemia (no coronary perfusion) and for 60 min after reinstating coronary
      perfusion (reperfusion). Hearts were then harvested and treated appropriately for
      analysis of infarct size. Exposure to the MLP diet in utero significantly
      increased systolic blood pressure at 4 and 8 weeks of age (6-13 mmHg increase; P
      < 0.001) and significantly impaired recovery of left ventricular developed
      pressure after ischaemia at 6 months of age in male offspring only (P < 0.003).
      Pre-treatment with NAC prevented this impairment of recovery in MLP male
      offspring and improved recovery in all females. Myocardial infarct size was not
      different between dietary groups after IR, but NAC pre-treatment significantly
      reduced the degree of infarction (P < 0.001). In conclusion, an MLP diet
      throughout gestation significantly impairs recovery of the 6-month-old adult rat
      heart to IR-induced injury in a sex-specific manner. Undernutrition during
      development may increase susceptibility to CHD by impairing recovery from
      coronary events.

PMID- 17445340
TI  - Identification of foods contributing to the dietary lipid profile of a
      Mediterranean population.
AB  - The identification of the target foods that most affect the fat content of a
      diet, independently whether or not they contain fat, can be a useful tool in the
      process of drawing up more effective dietary guidelines with nutritional
      education strategies more directed at the needs of each population. With this
      purpose, the contribution analysis designed by Block and colleagues and multiple
      linear regression models were applied to a representative sample of Catalonia.
      Olive oil was the food that provided the highest absolute and relative percentage
      of fat-derived energy intake and cheese the food that provided the highest
      percentage of saturated fat-derived energy intake. According to the results of
      the present work, during the last 10 years the consumption of fruits and
      vegetables in Catalonia has increased, more in women than men. The intake of
      white fish is significantly higher than the intake of blue fish, which should be
      increased in both men and women, and red meat is still the first meat source in
      this population. Special attention should be paid to the increasing sweet cereal
      consumption, which is a source of invisible fat to the diet.

PMID- 17445341
TI  - Transoesophageal echocardiography in monitoring, guiding, and evaluating surgical
      repair of congenital cardiac malformations in children.
AB  - OBJECTIVE: To evaluate the role of transoesophageal echocardiography and problems
      related to safety during the surgical repair of congenital cardiac malformations
      in children. METHODS: We examined the transoesophageal recordings made in 350
      children with congenital cardiac diseases, aged from 2 months to 17 years and 9
      months, with a median age of 2.7 years, tracings having been taken both before
      and after cardiopulmonary bypass. All patients had been scanned by transthoracic
      echocardiography before the operative procedures. RESULTS: Preoperative
      transoesophageal echocardiography added additional findings, or changed the
      diagnoses made using transthoracic echocardiography, in 33 cases (9.4%), among
      which the findings had therapeutic significance in 23 cases (6.6%) that altered
      the planned surgical procedures. Residual problems or sequels were detected by
      postoperative transoesophageal echocardiography in 57 cases (16.3%), with 13
      patients (3.7%) requiring instant intervention or return to bypass for
      modifications of the surgical procedures. We encountered no severe complications
      due to the performance of transoesophageal echocardiography. Mild complications
      occurred in only 2 patients (0.6%). CONCLUSIONS: Transoesophageal
      echocardiography is a useful tool with which to determine the strategies for
      treatment in the perioperative period, and to improve the quality of surgical
      procedures in children with congenital cardiac diseases. Complications were few,
      but still deserved careful attention to detail.

PMID- 17445342
TI  - Polymorphism C242T of the gene of the p22phox subunit for nicotinamide adenine
      dinucleotide phosphate oxidase, and erythrocytic antioxidant enzymes, in patients
      with tetralogy of Fallot.
AB  - BACKGROUND: Nicotinamide adenine dinucleotide phosphate oxidase of the vascular
      cell membrane is an important source of reactive oxygen species. The aim of our
      study was to evaluate the possible influence of the p22phox C242T gene
      polymorphism on blood pressure and some markers of oxidative stress in children
      with tetralogy of Fallot. METHODS: After surgical repair in early life, we
      recruited 38 children, aged 11.7 plus or minus 3.2 years, including 185 healthy
      individuals as controls for the purposes of establishing frequencies of alleles
      and genotypes. From this latter group, we matched a sub-sample of 53 healthy
      caucasian children, aged 11.0 plus or minus 1.0 years, in order to compare
      enzymic activities. RESULTS: The children with tetralogy of Fallot showed
      significantly lower values of low-molecular-weight protein tyrosine phosphatase,
      particularly in carriers of CC genotype for the p22phox gene, with values of
      145.2 plus or minus 77.4 micromol/g Hb/h, compared to controls, at 344.4 plus or
      minus 100.4 micromol/g Hb/h (p less than 0.001). Methemoglobin reductase activity
      in the patients with tetralogy was also lower in those with the CC genotype, at
      9.8 plus or minus 3.2 micromol/g Hb-1 min(-1) compared to 24.2 plus or minus 11.8
      micromol/g Hb(-1) min(-1) as measured in the controls (p less than 0.01). Lower
      systolic (p less than 0.05) and diastolic (p less than 0.01) blood pressures were
      also observed in the patients with tetralogy of Fallot. CONCLUSIONS: Patients
      with tetralogy of Fallot having the CC genotype may be at a higher state of
      oxidative stress than T allele carriers, a finding which could have prognostic
      implications. Long term follow-up of these patients, however, may be necessary in
      order to draw definite conclusions.

PMID- 17445343
TI  - Interference of electrocardiographic recordings by a mobile telephone.
AB  - The ownership of mobile telephones is now almost universal amongst the teenage
      population of the United Kingdom. Such telephones are a potential source of
      electromagnetic interference to medical equipment. We describe a case of
      troublesome interference with an electrocardiogram recording in a teenage patient
      whose mobile telephone was left switched on during a visit to hospital. This is
      likely to be a common reason for poor quality electrocardiographic recordings.

PMID- 17445344
TI  - Aneurysmal formation in the setting of muscular ventricular septal defects.
AB  - OBJECTIVE: To emphasize the formation of fibrous aneurysmal structures in the
      setting of muscular ventricular septal defects METHODS: Among patients with
      muscular ventricular septal defects followed in our institute, we described six
      who were diagnosed with formation of fibrous aneurysms. Of the patients, one was
      female and others were male. The age at diagnosis ranged from eight days to 16
      years. In one, the defect opened between the ventricular inlets, but in the
      others the defects occupied the middle part of the apical trabecular septum.
      RESULTS: The sizes of defects at initial echocardiographic evaluation ranged from
      2.9 to 8 millimetres. The period of follow up for four patients was from 5 months
      to 7 years, one patient could not be followed up, and the other had already been
      diagnosed when first seen in our Institution. In our second and third patients,
      no aneurysm was seen during the initial echocardiographic evaluation, and it was
      recognized during follow-up. In these two patients, sequential echocardiographic
      examinations showed that the formation of the aneurysm made the defect smaller,
      with it almost closing in one. CONCLUSION: Although seen most frequently in the
      setting of perimembranous defects, fibrous aneurysms can also form adjacent to,
      and reduce the size of, muscular ventricular septal defects.

PMID- 17445345
TI  - Acquired stenosis of normally connected pulmonary veins.
AB  - Pulmonary venous stenosis has been a challenge to paediatric cardiologists and
      surgeons. In spite of significant improvements in the management and outcome of
      various congenital cardiac problems, the prognosis of this condition continues to
      be dismal. Acquired stenosis of the pulmonary veins has been described in the
      adult population, especially after radiofrequency ablation for atrial
      arrhythmias. The outcome of this condition has generally been described to be
      favourable in the long term. Acquisition of pulmonary venous stenosis in
      childhood has a very different outcome, and is not a very well recognised entity,
      with symptoms and signs which are non-specific. We present 7 infants who, when
      first assessed, had normal pulmonary veins, but who subsequently acquired
      stenoses of the veins, with very significant resultant morbidity and mortality.

PMID- 17445346
TI  - Comparison of the uptake and secretion of carotene and xanthophyll carotenoids by
      Caco-2 intestinal cells.
AB  - Carotenoids have been shown to have potential beneficial effects on human health
      which has led to an increasing interest in the study of their bioavailability. A
      Caco-2 cell model, as previously described, was employed to examine the
      percentage transfer of the carotenoids alpha-carotene, beta-carotene, lycopene,
      astaxanthin, beta-cryptoxanthin, lutein and zeaxanthin through an intact, highly
      differentiated Caco-2 cell monolayer at a range of different amounts. Our results
      show that astaxanthin, a carotenoid with powerful antioxidant capacity, had the
      highest percentage transfer overall. We examined the cellular uptake and
      secretion of lutein and zeaxanthin to compare two structurally similar
      carotenoids. Both were efficiently transported through the monolayer with a range
      between 5.1 (sem 1.2) % to 20.2 (sem 3.3) % and 5.5 (sem 2.5) % to 13.4 (sem 4) %
      for lutein and zeaxanthin, respectively. These carotenoids were compared to each
      other at each added amount and no significant difference was observed between the
      two xanthophylls. The carotene carotenoids alpha-carotene, beta-carotene and
      lycopene and the xanthophyll beta-cryptoxanthin were also examined and had lower
      uptake and secretion values when compared to lutein, zeaxanthin and astaxanthin.
      The xanthophyll beta-cryptoxanthin was also not significantly different when
      compared to the carotene carotenoids. Data generated from this study compares
      well with in vivo bioavailability studies. Furthermore, the model provides
      comparative data on the relative absorption and transfer of seven different
      carotenoids. Our data indicate that lower amounts of carotenoids were absorbed
      and transferred more efficiently than higher amounts suggesting a saturation
      effect at higher exposure.

PMID- 17445347
TI  - Expression of DNA repair and metabolic genes in response to a flavonoid-rich
      diet.
AB  - A diet rich in fruit and vegetables can be effective in the reduction of
      oxidative stress, through the antioxidant effects of phytochemicals and other
      mechanisms. Protection against the carcinogenic effects of chemicals may also be
      exerted by an enhancement of detoxification and DNA damage repair mechanisms. To
      investigate a putative effect of flavonoids, a class of polyphenols, on the
      regulation of the gene expression of DNA repair and metabolic genes, a 1-month
      flavonoid-rich diet was administered to thirty healthy male smokers, nine of whom
      underwent gene expression analysis. We postulated that tobacco smoke is a
      powerful source of reactive oxygen species. The expression level of twelve genes
      (APEX, ERCC1, ERCC2, ERCC4, MGMT, OGG1, XPA, XPC, XRCC1, XRCC3, AHR, CYP1A1) was
      investigated. We found a significant increase (P < 0.001) in flavonoid intake.
      Urinary phenolic content and anti-mutagenicity did not significantly change after
      diet, nor was a correlation found between flavonoid intake and urinary phenolic
      levels or anti-mutagenicity. Phenolic levels showed a significant positive
      correlation with urinary anti-mutagenicity. AHR levels were significantly reduced
      after the diet (P = 0.038), whereas the other genes showed a generalized up
      regulation, significant for XRCC3 gene (P = 0.038). Also in the context of a
      generalized up regulation of DNA repair genes, we found a non-significant
      negative correlation between flavonoid intake and the expression of all the DNA
      repair genes. Larger studies are needed to clarify the possible effects of
      flavonoids in vivo; our preliminary results could help to better plan new studies
      on gene expression and diet.

PMID- 17445348
TI  - Jerusalem artichoke and chicory inulin in bakery products affect faecal
      microbiota of healthy volunteers.
AB  - A study was conducted to test the effects of Jerusalem artichoke inulin (JA) or
      chicory inulin (CH) in snack bars on composition of faecal microbiota,
      concentration of faecal SCFA, bowel habit and gastrointestinal symptoms. Forty
      five volunteers participated in a double-blind, randomized, placebo-controlled,
      parallel-group study. At the end of a 7 d run-in period, subjects were randomly
      assigned to three groups of fifteen subjects each, consuming either snack bars
      with CH or JA, or snack bars without fructans (placebo); for 7 d (adaptation
      period), they ingested one snack bar per day (7.7 g fructan/d) and continued for
      14 d with two snack bars per day. The composition of the microbiota was monitored
      weekly. The consumption of CH or JA increased counts of bifidobacteria (+1.2
      log10 in 21 d) and reduced Bacteroides/Prevotella in number and the Clostridium
      histolyticum/C. lituseburense group in frequency at the end of intervention (P <
      0.05). No changes in concentration of faecal SCFA were observed. Consumption of
      snack bars resulted in a slight increase in stool frequency. Stool consistency
      was slightly affected in subjects consuming two snack bars containing CH or JA
      per day (P < 0.05). Consumption of CH or JA resulted in mild and sometimes
      moderate flatulence in a few subjects compared to placebo (P < 0.05). No
      structural differences were detected between CH and JA before and after
      processing. In conclusion, adaptation on increased doses of CH or JA in bakery
      products stimulates the growth of bifidobacteria and may contribute to the
      suppression of potential pathogenic bacteria.

PMID- 17445349
TI  - Effect of early feed restriction on myofibre types and expression of growth
      related genes in the gastrocnemius muscle of crossbred broiler chickens.
AB  - The purpose of this study was to investigate the immediate and long-term effects
      of early feed restriction (ER) on morphology and gene expression of lateral
      gastrocnemius muscle. Newly hatched crossbred broiler chickens were allocated
      into control and ER groups, the latter being free-fed on alternate days from
      hatch to 14 days of age (14 d), followed by ad libitum feeding as the control
      group until 63 d. The lateral gastrocnemius muscle was taken at 14 and 63 d,
      respectively for myofibre typing by both myosin ATPase staining and relative
      quantification of myosin heavy chain (MyHC) mRNA for slow-twitch (SM), red fast
      twitch (FRM) and white fast-twitch (FWM) myofibres. The body weight and lateral
      gastrocnemius weight were significantly lower in the ER group, accompanied by
      significantly reduced serum triiodothyronine. The ER group exhibited
      significantly higher SM and FRM MyHC expression at 14 d, but lower SM expression
      at 63 d. Myosin ATPase staining revealed a similar pattern. The percentage of SM
      was higher at 14 d while lower at 63 d in the ER group. These morphological
      changes were accompanied by changes of mRNA expression for growth-related genes.
      The ER group expressed lower insulin-like growth factor I (IGF-I) and higher IGF
      I receptor (IGF-IR) at 14 d, yet significantly increased growth hormone receptor
      and IGF-IR mRNA at 63 d. These results indicate that ER may delay the slow to
      fast myofibre conversion as an immediate effect, but would result in a lower
      percentage of slow fibres owing to compensatory growth in the long term, which
      involves changes of mRNA expression for the growth-related genes in the muscle.

PMID- 17445350
TI  - Effects of arachidonate-enriched triacylglycerol supplementation on serum fatty
      acids and platelet aggregation in healthy male subjects with a fish diet.
AB  - The changes in fatty acid composition of serum and in platelet aggregation
      induced by supplementation of arachidonate-enriched TAG were investigated in
      twenty-four healthy Japanese men in a double-blind, placebo-controlled study. The
      arachidonate-enriched TAG ingested was an edible oil, extracted and purified from
      a biomass of submerged fermented Mortierella alpina. Mean daily intake of fish
      and shellfish by subjects was 87.2 (se5.3) g/d, while dietary intakes of
      arachidonic acid (ARA) by the ARA group and placebo group were 175 (se12) and 179
      (se13) mg/d, respectively. In the ARA group, after 2-week supplementation of 838
      mg ARA/d, ARA concentration in serum phospholipids was increased from 9.6 (se0.4)
      to 13.7 (se0.4) g/100 g total fatty acids, and was significantly different from
      that in the placebo group (P < 0.001). This level was maintained for 4 weeks but
      returned to baseline level after a 4-week washout period. Linoleic acid
      concentration in serum phospholipids decreased from 19.2 (se0.8) to 16.3 (se0.6)
      g/100 g total fatty acids in the ARA group. Similarly, ARA content of serum TAG
      increased after ARA supplementation. Neither the EPA nor DHA content of serum
      phospholipids or TAG was altered by ARA supplementation. The platelet aggregation
      induced in platelet-rich plasma by adding adenosine diphosphate, collagen and
      ARA, physical characteristics of subjects, and biochemical parameters were
      unchanged throughout the test period. These findings suggest that ARA
      concentration in serum phospholipids and TAG can be safely increased by
      supplementation of arachidonate-enriched TAG oil.

PMID- 17445351
TI  - Effect of chronic consumption of almonds on body weight in healthy humans.
AB  - Small changes of diet may reduce CVD risk. One example is the inclusion of nuts.
      They are rich in fibre, unsaturated fatty acids and phytonutrients. However,
      their fat content and energy density raise concerns that chronic consumption will
      promote weight gain. Randomised intervention studies are required to evaluate
      whether this concern is well founded. This study's aim was to determine if the
      inclusion of a 1440 kJ serving of almonds in the daily diet results in positive
      energy balance, and body composition change. During a 23-week cross-over design
      study, participants were required to consume almonds for 10 weeks and were
      provided no advice on how to include them in their diet. For another 10 weeks
      (order counter-balanced), participants followed their customary diet and there
      was a 3-week washout between. The study group consisted of twenty women.
      Potential mechanisms of energy dissipation were measured. Ten weeks of daily
      almond consumption did not cause a change in body weight. This was predominantly
      due to compensation for the energy contained in the almonds through reduced food
      intake from other sources. Moreover, inefficiency in the absorption of energy
      from almonds was documented (P < 0.05). No changes in resting metabolic rate,
      thermic effect of food or total energy expenditure were noted. A daily 1440 kJ
      serving of almonds, sufficient to provide beneficial effects on cardiovascular
      risk factors, may be included in the diet with limited risk of weight gain.
      Whether this can be generalised to other high-fat energy dense foods warrants
      evaluation.

PMID- 17445352
TI  - Energy and nutrient intakes by pre-school children in Flanders-Belgium.
AB  - The objective of this cross-sectional study was to investigate energy and
      nutrient intakes in pre-school children in Flanders-Belgium, using multistage
      clustered sampling. Diets of 661 children (338 boys; 323 girls) between 2.5 and
      6.5 years old were assessed, with parentally reported 3 d estimated diet records.
      Usual energy and nutrient intakes were compared with national and international
      recommendations. Statistical modelling was used to account for within-individual
      variation. Mean daily energy intakes (boys, 6543 kJ; girls, 5757 kJ) approached
      the estimated energy requirements (EER) (boys, 6040 kJ; girls, 5798 kJ) for
      children < 4 years old. For children at least 4 years old, mean energy intakes
      (boys, 6408 kJ; girls, 5914 kJ) were below the EER of 6995 and 6740 kJ/d,
      respectively. Mean energy percentage (en%) derived from saturated fatty acids
      (SFA) (13-14 en%) was above the acceptable macronutrient distribution range
      (AMDR) upper level of 12 en%. Mean percentages derived from MUFA (10-11 en%) and
      PUFA (4-5 en%) were below the AMDR lower levels of 12 and 8 en%, respectively.
      For fibre, iron and vitamin D intakes, < 15 % of the children reached the
      recommended dietary allowances. Everybody exceeded the tolerable upper intake
      levels for sodium. Although diets in Belgian children were adequate in most
      nutrients, the implications of low iron, vitamin D and fibre intakes should be
      investigated. Furthermore, this affluent diet, characterised by SFA, MUFA and
      PUFA intakes differing from the recommendations and excessive sodium intakes,
      might increase the risk for CVD in later life.

PMID- 17445353
TI  - Percutaneous closure of ventricular septal defects.
AB  - BACKGROUND: Surgical closure of ventricular septal defects has been performed for
      many years, and is considered as the gold standard for treatment. It remains
      associated with morbidity and mortality. Transcatheter techniques have been
      developed in the last 10 years as a possible alternative to conventional surgery.
      METHODS: The procedure is performed under general anaesthesia, and with
      continuous fluoroscopic and transesophageal echocardiographic guidance. Devices
      of the Amplatzer family, two in particular, have achieved a large popularity in
      clinical practice, and are currently the devices most commonly used to close
      muscular and perimembranous ventricular septal defect percutaneously. RESULTS:
      Data from literature show that successful closure of muscular defects is obtained
      in around 96% of patients, with a rate of major complication of around 2%.
      Pooling data from the literature shows that successful closure of perimembranous
      defects is also obtained in 96% of patients, again with major acute complications
      in around 2%. The major problem is the occurrence of complete atrioventricular
      block, reported in 1.7% of subjects. Acquired defects can occur as residual leaks
      after surgical closure, or as consequence of myocardial infarction. There are
      very few data concerning percutaneous closure of postoperative residual defects.
      As for the surgical approach, in patients with post-myocardial defects the
      success rate of percutaneous closure is around 88%, with a mortality of 22%.
      CONCLUSIONS: Nowadays, in experienced hands, percutaneous closure is a safe and
      effective procedure. In selected patients, closure of congenital or acquired
      muscular and perimembranous ventricular septal defects can be considered a real
      alternative to the standard surgical approach, with the advantage of a
      significantly reduced rate of mortality and complications.

PMID- 17445354
TI  - The Pakistan (Lahore) cochlear implant programme: issues relating to implantation
      in a developing country.
AB  - The Pakistan cochlear implant programme was started in Lahore in August 2000. It
      was initially established with the technical support of the Manchester cochlear
      implant team. There are no government resources available for cochlear
      implantation in Pakistan and the cost of cochlear implantation is met by the
      candidates and their families. Up till December 2005, 52 individuals have been
      implanted. Forty-four (84.6 per cent) of these patients were children and eight
      (15.4 per cent) patients were adults. Congenital deafness (94 per cent) is the
      main aetiological factor in children. Seventy-six per cent of these children were
      born to blood related parents. All patients received a Med-El Combi 40+ device.
      The listening progress profile, the meaningful auditory integration scale and the
      meaningful use of speech scale were used to assess the auditory performance in
      children. Thirty-nine children achieved an average listening progress profile
      score of 37.7 after 12 months of implantation. The overall rate of major and
      minor complications was 11.5 per cent. Failure rate for the device itself has
      been 3.8 per cent. In addition to considering these preliminary outcomes and
      funding issues, the problems of setting up a cochlear implant programme in a
      developing country are discussed.

PMID- 17445355
TI  - Voice outcomes following transoral laser microsurgery for early glottic squamous
      cell carcinoma.
AB  - INTRODUCTION: Early glottic cancer may be treated with primary radiotherapy or
      transoral laser microsurgery with comparable survival. The choice of therapy
      therefore depends on patient preference after discussion of risks, benefits and
      alternatives. MATERIALS AND METHODS: All previously untreated patients undergoing
      transoral laser microsurgery for T1 or T2 glottic cancer at St Vincent's Hospital
      between July 1997 and December 2004 had their staging and demographics recorded.
      Surgery was categorised according to the European Laryngological Society. A voice
      recording was made pre-operatively then at 12 weeks post-operatively and scored
      by two independent speech therapists on the Oates Russell Voice Profile - a scale
      of zero (normal) to five (severe dysphonia). Follow up was for a minimum of two
      years. RESULTS AND ANALYSIS: Fifty-three patients with a mean age of 56 were
      included. The observed survival was T1 89.4 per cent and T2 85.3 per cent after a
      mean follow up of 47 months. Nineteen patients staged T1 underwent cordectomy. A
      second procedure was required in 22.2 per cent, however, none required a
      laryngectomy. Thirty-four patients staged T2 underwent hemilaryngectomy. A second
      procedure was required in 41.2 per cent including 8.8 per cent requiring salvage
      laryngectomy. One patient died with unresectable nodal disease. The mean Oates
      Russell Voice Profile for T1 disease was 2.37 and for T2 2.68 (range 1 to 4)
      indicating a mild (2) to moderate (3) degree of voice impairment. CONCLUSIONS:
      Survival outcomes following transoral laser microsurgery are comparable to
      treatment with radiotherapy. Voice impairment is usually mild to moderate
      following transoral laser microsurgery for early glottic cancer but overall may
      be greater than in radiotherapy patients. The repeatability of transoral laser
      microsurgery may result in a lower laryngectomy rate compared with published
      series using radiotherapy.

PMID- 17445356
TI  - Vocal outcomes following subepithelial infiltration technique in microflap
      surgery: a review of 30 cases.
AB  - Understanding of the anatomy and physiology of the vocal folds, availability of
      better diagnostic tools and precise instruments has spurred the development of
      newer techniques for the management of benign lesions arising in the vocal folds.
      As the propensity of the superficial lamina propria to regenerate is minimal, it
      is of paramount importance to maximally preserve it. Microflap surgery of the
      vocal folds is based on this principle. There exists a dichotomy in opinion
      regarding the role of subepithelial infiltration in microflap surgery; the
      disadvantages cited being possible confusion of the surgical plane following
      infiltration and hydrodissection of the normal basement membrane from the
      superficial layer of the lamina propria. A prospective study was therefore
      carried out in 30 cases of benign glottic lesions and microflap surgery was
      performed with and without infiltration in similar pathologic lesions. The vocal
      outcomes i.e. fundamental frequency, jitter, shimmer and maximum phonation time
      were audited. The advantages of this technique with a review of the literature
      are discussed.

PMID- 17445358
TI  - From a descriptive toward an explicative growth-based model on immature Oulema
      duftschmidi (Coleoptera: Chrysomelidae) development at different temperatures.
AB  - The developmental rates of Oulema duftschmidi (Redtenbacher) eggs, larvae, and
      pupae were studied at different constant temperatures. A linear regression model
      was fitted to the data obtained in this and in a previous study within a
      temperature range where the rate proportionally increases with temperature.
      Ratios of SEs to the mean thermal constant and to the mean developmental
      threshold indicated that reliable estimates have been obtained for the three life
      stages. Within the framework provided by the metabolic theory of ecology, a
      growth-based model was evaluated to explain developmental rates in the entire
      temperature range permissive of development of the three life stages. The model
      is based on component functions describing growth patterns through time,
      temperature-dependent consumption rates of biomass, transformation of consumed
      food into body biomass change, and respiration rates with respect to temperature.
      Experimental data were used for the selection and validation of models and for
      the estimation of the parameters of different regression models. Limitations and
      opportunities for using the growth-based model to explain developmental rates are
      discussed. An empirical function was used to describe the variability of
      developmental rates.

PMID- 17445357
TI  - Venlafaxine exhibits an anti-inflammatory effect in an inflammatory co-culture
      model.
AB  - Growing evidence indicates immunoregulatory effects of various antidepressants.
      Through the interaction of the nervous and immune systems, the norepinephrine
      serotonin system was shown to modulate inflammatory CNS diseases. Thus, we
      examined the norepinephrine-serotonin reuptake inhibitor venlafaxine in an
      astroglia-microglia co-culture model which allows mimicking of an inflammatory
      milieu by increasing the cultured microglial fraction. Astrocytic membrane
      resting potential and intercellular coupling, two markers becoming severely
      impaired under inflammation, were assessed with the patch-clamp technique. We
      measured IL-6, IL-10, IFN-gamma and TGF-beta concentrations and analysed
      phenotypic changes of microglia. We found (i) a reversal of the inflammation
      induced depolarization effect on the membrane resting potential, (ii) an
      augmentation of TGF-beta release with a concomitant reduction in the secretion of
      pro-inflammatory IL-6 and IFN-gamma, and (iii) a significant change of microglial
      phenotype from activated to resting morphology. Our data clearly indicate anti
      inflammatory properties of venlafaxine which might be a result of monoamine
      mediated immunomodulation.

PMID- 17445359
TI  - Reproductive potential of overwintering, F1, and F2 female boll weevils
      (Coleoptera: Curculionidae) in the Lower Rio Grande Valley of Texas.
AB  - The feeding and oviposition activity of overwintering boll weevils, Anthonomus
      grandis grandis (Boheman), and seasonal fluctuations in development, survival,
      and reproduction of progeny of overwintering and first- and second-generation
      boll weevil females were determined in the laboratory at 27 degrees C, 65% RH,
      and a photoperiod of 12:12 (L:D) h. During the cotton-free period in the Lower
      Rio Grande Valley, female boll weevils without access to cotton resorb their
      unlaid eggs and enter reproductive diapause. However, when they were provided
      daily with greenhouse-grown cotton squares, commencement of oviposition began
      after 7, 15, or 20 d, depending on when they were captured. Females captured
      later in the winter fed longer before laying eggs than those captured in the
      early fall, suggesting that it may take females longer to terminate diapause the
      longer they have been dormant. The rate of feeding by females was significantly
      less during the winter months, and this may have affected the rate of diet
      mediated termination of dormancy. Females of the first and second generations
      after the overwintering generation produced a significantly higher percentage of
      progeny surviving to adulthood and a higher proportion of these progeny were
      females. Offspring development time from overwintering female parents was
      significantly longer than that from first and second generations under the same
      laboratory conditions. The total number of lifetime eggs produced by females of
      the second generation during the cotton-growing season were approximately 9.9
      fold higher than for overwintering females and 1.5-fold higher than for first
      generation females. Life table calculations indicated that the population of
      second-generation boll weevils increased an average of 1.5-fold higher each
      generation than for females of the first generation and 22.6-fold higher than for
      overwintering females. Our data showed variation in boll weevil survival,
      development, and reproductive potential among the overwintering and first- and
      second-generation females, suggesting inherent seasonal fluctuations in these
      parameters.

PMID- 17445360
TI  - Effect of temperature on life history of Aphidius colemani and Aphidius
      matricariae (Hymenoptera: Braconidae), two parasitoids of Aphis gossypii and
      Myzus persicae (Homoptera: Aphididae).
AB  - The performance of two aphid parasitoids, Aphidius colemani Viereck and Aphidius
      matricariae (Haliday), against Aphis gossypii Glover on greenhouse cucumber
      (Cucumis sativus L.) and Myzus persicae (Sulzer) on sweet pepper (Capsicum annuum
      L.) were evaluated at various constant temperatures. Biological parameters of
      both parasitoids including developmental time, pupal survivorship, percentage of
      parasitism, and sex ratio of the progeny were studied at 5, 10, 15, 20, 25, 30,
      and 35 degrees C. At 25 degrees C, an average of 10.0 +/- 1.1 and 9.8 +/- 1.1 d
      was needed for A. colemani to complete its development from oviposition to adult
      eclosion on A. gossypii and M. persicae, respectively. The corresponding average
      times needed for A. matricariae were 11.9 +/- 0.9 and 11.5 +/- 1.1 d,
      respectively. The lower developmental thresholds for A. colemani reared on A.
      gossypii and M. persicae were estimated from linear regression equations to be
      2.97 and 2.65 degrees C, respectively, whereas these values for A. matricariae
      were 3.37 and 3.51 degrees C, respectively. Parasitization rate of both
      parasitoid species, recorded as percent aphids mummified, increased almost
      linearly with increasing temperature to reach a maximum at 25 degrees C and
      decreased at 30 degrees C. The optimal temperatures for development of A.
      colemani and A. matricariae were approximately 30 and 25 degrees C, respectively,
      and high mortality occurred at higher temperatures. The Lactin 2 and Briere 1
      developmental models were accepted based on their excellent goodness-of-fit to
      the data (residual sum of square and coefficient of determination) and estimable
      temperature thresholds and are strongly recommended for the description of
      temperature-dependent development of A. colemani and A. matricariae.

PMID- 17445361
TI  - Males of Hylamorpha elegans burmeister (Coleoptera: Scarabaeidae) are attracted
      to odors released from conspecific females.
AB  - The behavioral responses of Hylamorpha elegans L. (Coleoptera: Scarabaeidae,
      Rutelinae) to the semiochemicals released from conspecific individual adults were
      studied, with particular attention paid to female attraction of males. Odors
      released from virgin females significantly attracted male conspecifics in both
      the field and laboratory olfactometer and wind tunnel bioassays. However, females
      did not attract other females, and males attracted no one. The response of male
      H. elegans to (1) compounds (1,4-hydroquinone and 1,4-benzoquinone) released only
      by unmated females; (2) the essential oil of the secondary host (Nothofagus
      obliqua); and (3) the blend of 1,4-hydroquinone and 1,4-benzoquinone with N.
      obliqua essential oil was studied. The blend of 1,4-benzoquinone mixed with
      essential oil at the trial concentration was attractive with males. The same
      response was found with 1,4-hydroquinone alone. The essential oil did not have
      the expected attractant effect on conspecific males. These results suggest that,
      when combined with essential oil, 1,4-benzoquinone may function in the sexual
      behavior of males and females. These findings are discussed in terms of the
      ecological role of this putative sexual pheromone and its potential use in a
      strategy of control of this pest.

PMID- 17445362
TI  - Improved semiochemical-based trapping method for old-house borer, Hylotrupes
      bajulus (Coleoptera: Cerambycidae).
AB  - The old-house borer, Hylotrupes bajulus (Linnaeus) (Coleoptera: Cerambycidae),
      has been a very serious pest of structural timber in many parts of the world. The
      available semiochemical-based trapping method typically results in low capture
      rates. In this study, efforts were made to improve the semiochemical-based
      trapping method using screen cage assays conducted in the greenhouse. Ground
      traps baited with two vials of (3R)-ketol + 1-butanol (pheromone baited) caught
      >21.0% adults than the alternative trap and were seen to be superior to ramp
      traps baited with identical compounds. Based on adult catches with pheromone
      baited traps with different colors, attraction of H. bajulus adults to black was
      significantly greater than other colors, followed by brown, gray and yellow, red,
      white, green, and blue. No differences were found in adult catches to pheromone
      baited traps with respect to different trap sizes. There were no statistical
      differences between the different semiochemicals tested. Therefore, black ground
      traps baited with two vials of (3R)-ketol + 1-butanol plus two vials of ethyl
      acetate can be effective in the monitoring and potential control of H. bajulus.

PMID- 17445363
TI  - Distribution and dynamics of Japanese beetles along the Indianapolis Airport
      perimeter and the influence of land use on trap catch.
AB  - As part of a program to minimize the accidental transportation of Japanese
      beetles (Popillia japonica) through cargo aircraft to areas where they are not
      established, a 4-yr trapping project was initiated to study the relative
      distribution and dynamics of the beetles along a trap line around the
      Indianapolis International Airport. Land use influence on beetle abundance (trap
      catch) was assessed using a geographic information system. Trap catch was
      consistently high in some locations and low in others. In general, high trap
      catches occurred near agronomic land planted with corn or soybeans, which are
      both preferred hosts of adult beetles. Low trap catches generally occurred in
      areas lacking preferred host plants. The amount of agronomic land within 500 m of
      the traps was always positively correlated with trap catch. Average trap catches
      were highly correlated by location from year to year, indicating stability of the
      relative distribution of the beetles along the trap line. Because high trap
      catches consistently occurred in the same locations, it can be inferred that
      trapping can be an effective method to monitor Japanese beetle populations.
      Taking airport-owned agronomic land out of corn and soybean production near the
      cargo terminals may reduce beetle activity in these areas.

PMID- 17445364
TI  - Effects of invasive eastern redcedar on capture rates of Nicrophorus americanus
      and other Silphidae.
AB  - Because of fire suppression and improper land management, native eastern
      redcedar, Juniperus virginiana L., is invading many grassland areas. Among these
      areas are the Loess Canyons of southeastern Lincoln County, NE, which support a
      large population of the federally endangered American burying beetle, Nicrophorus
      americanus Olivier. In the past 30 yr, cedar encroachment has covered >30% of
      this landscape and is increasing at a rate of 2% per year. The effects of cedar
      trees on remaining populations of American burying beetle are currently unknown.
      In this study, we sampled two sites in Lincoln County, NE, by placing paired
      baited pitfall traps (N = 16) in cedar-dominated and open grassland habitats
      during June and August 2004 and 2005. We collected significantly more Silphidae,
      including American burying beetle in open habitats. All American burying beetle
      were marked and released. The recapture rate of these beetles was two times
      higher in cedar sites than in open sites. Among the Silphidae, only Nicrophorus
      orbicollis Say was collected significantly more often in cedar areas. The results
      of this study indicate that cedars reduce numbers of most silphid species, likely
      by limiting their ability to forage for carrion, a required resource for feeding
      and reproduction. This is the first study to directly examine the impact of cedar
      on Silphidae, and our results have important implications in the Great Plains and
      beyond. However, future studies must examine the impacts of cedar management,
      including mechanical control or prescribed fire, on American burying beetle and
      other silphid species.

PMID- 17445365
TI  - Hoverfly (syrphidae) communities respond to varying structural retention after
      harvesting in canadian peatland black spruce forests.
AB  - Variable retention harvesting (VRH), in which trees are removed at variable
      intensity and spatial configuration across the landscape, retains greater forest
      structural heterogeneity than traditional clear-cut harvesting and is being
      recommended as an alternative for sustainable management of the boreal forest.
      Little is known about its effects on forest fauna; thus, we studied the influence
      of one type of VRH (harvesting with advanced regeneration [HARP]) on the
      Syrphidae (Diptera) community in northern Ontario forests of peatland black
      spruce (Picea mariana). We examined the effects of varying structural retention
      (from unharvested through partial retention to clear-cut) on syrphid species
      richness and abundance, and abundance of functional assemblages. Greater species
      richness and population abundances were found generally in harvested than in
      unharvested forests. Overall species richness and the abundance of four species
      (Platycheirus rosarum, Toxomerus marginatus, Xylota annulifera, and X.
      tuberculata) and larval predators were all higher in both clear-cut sites and
      those with structural retention than in unharvested sites. Similarly, overall
      species richness and the abundance of nine species were higher in clear-cut than
      in unharvested sites. Species responses are discussed in an ecological context.
      Differences among the levels of forest retention harvesting were relatively minor
      compared with those of the clear-cut and unharvested area, suggesting that local
      habitat characteristics may play a more important role in determining the syrphid
      community than the landscape configuration. However, a landscape level effect was
      evident, suggesting that syrphids may be useful in reflecting changes in stand
      structure at the landscape scale.

PMID- 17445366
TI  - Comparative use of Mindarus abietinus (Homoptera: Aphididae) by two coccinellids
      (Coleoptera: Coccinellidae), the native Anatis mali and the exotic Harmonia
      axyridis, in a Christmas tree plantation.
AB  - The exotic coccinellid Harmonia axyridis (Pallas) recently expanded its range
      into eastern Canada and elsewhere in North America. We hypothesized that this
      coccinellid should be less well adapted to the prey Mindarus abietinus Koch. on
      balsam fir trees than the native coccinellid Anatis mali (Say), which evolved in
      close association with aphids on conifers in North America. We compared, under
      field conditions, prey use by both species by collecting data on their synchrony
      with M. abietinus, their prey searching and predation behaviors, life stage
      distribution in fir canopy, and their overall reproductive success in this
      system. The seasonal life cycle of A. mali was better synchronized with that of
      M. abietinus compared with that of H. axyridis. In spring, A. mali adults
      appeared nearly 2 wk earlier on trees than H. axyridis and were active predators
      of the aphid fundatrices. A. mali oviposition thus began before the aphid
      population started to grow, and its larvae were most active during peak aphid
      colonies. Behavioral observations showed that both adults and larvae of the
      native A. mali searched for prey more actively than those of H. axyridis.
      Distribution of life stages also showed that eggs and pupae had different
      distributions on trees and that the adult-to-adult net reproductive rate of A.
      mali was three times higher than that of H. axyridis. Thus, the native A. mali
      was better adapted than H. axyridis to prey on M. abietinus, possibly because it
      evolved for a much longer period of time with this prey in conifer habitats.

PMID- 17445367
TI  - Do larvae of species in macrolepidopteran assemblages share traits that influence
      susceptibility to parasitism?
AB  - Research on how morphology, behavior, and life histories of insects determine
      their susceptibility to parasitism has primarily focused on the traits of single
      host species. Very little research has been conducted attempting to determine if
      similarities or differences in the traits of co-occurring species, on a single
      plant or in a habitat, influence levels of parasitism imposed on any member of an
      assemblage. In this study, we use categorical and regression tree analyses to
      determine which traits of the larvae of macrolepidopteran species are associated
      with highest levels of parasitism. Of a variety of morphological, behavioral, and
      ecological traits of 72 species (representing eight families), caterpillar color
      was the trait that had the greatest influence on susceptibility to parasitism.
      The highest levels of parasitism were associated primarily with green larvae.
      These results suggest that the herbivore species composition and, specifically,
      the traits possessed by the species may influence community or assemblagewide
      patterns of parasitism. That is, sharing of traits that enhance host finding and
      successful parasitism may result in associational susceptibility to parasitism,
      whereas co-occurrence with species that differ morphologically, behaviorally, or
      ecologically may reduce the likelihood of parasitism and thus result in
      associational resistance. The concepts of associational resistance and
      susceptibility have historically been restricted to plant-plant interactions. The
      extension of these concepts to herbivores is novel. If found to be widespread,
      these interactions can have significant impacts on our expectations of the
      effectiveness of biological control agents.

PMID- 17445368
TI  - Recovery of ground ant (Hymenoptera: Formicidae) communities six years after a
      major environmental disaster.
AB  - The recovery of ant communities at the Guadiamar River bank (southwest Spain) was
      studied across 5 yr, after an environmental disaster caused by the spill of toxic
      sludge over the river caused by a mine accident. Three affected and three control
      sites were sampled from 2000 to 2004 using pitfall traps. The last year of study,
      a more exhaustive sampling was conducted at the affected area (eight sampling
      sites). Additionally, four adjacent study sites not affected by the toxic spill
      were also studied. Ants showed clear responses to the restoration of the area.
      Mean ant species richness in spillage affected sites showed a significant
      increase over the 5 yr. Moreover, multivariate analysis showed distinct changes
      of ant community composition of the affected area over the years that were not
      observed in control sites. Six years after the disaster, one half of the species
      recorded in control sites were also present in the affected area, with only one
      species exclusive to this area, Cardiocondyla mauritanica Forel (tramp species).
      However, not only habitat specialist species but also some generalist and
      conspicuous species within the river basin are not present along the affected
      area, including species of the genera Camponotus, Messor, Cataglyphis, and
      Aphaenogaster. This study shows an incipient recovery of ant communities 6 yr
      after a major environmental disturbance, highlighting the absence of any invasive
      ant species in the restored area.

PMID- 17445369
TI  - Distribution of carabid beetles (Coleoptera: Carabidae) across a forest-grassland
      ecotone in southwestern China.
AB  - This paper studied the occurrence of carabid beetles (Coleoptera: Carabidae) in
      the forest edge, the adjacent forest interior, and the surrounding grassland in
      southwestern China. Beetles were collected with pitfall traps along five
      replicated transects. Forest species rarely penetrated into the grassland from
      the forest interior, and the grassland specialists were not found in the forest
      interior. The forest edge hosted additional species from the adjacent grassland
      that increased its overall species richness. Nearly all forest species (23 of 24
      species) and grassland species (13 of 15 species) can be found in the forest
      edge. Carabids of the forest edge were more similar to those of the forest
      interior than to those of the grassland by ordination and cluster analysis. Based
      on the specificity and fidelity, carabids can be distinguished into five species
      groups: habitat generalists, grassland-associated species, forest generalists,
      forest specialists, and edge-associated species. Multiple linear regression
      analysis showed that canopy cover and/or shrub cover were the most important
      factors in determining the richness, abundance, and diversity of carabids. The
      forest edge may serve as a transition zone for dispersal and re-colonization of
      carabid beetles from adjacent habitats and therefore is important for natural
      conservation.

PMID- 17445370
TI  - Effects of tillage on the activity density and biological diversity of carabid
      beetles in spring and winter crops.
AB  - The effects of tillage regimen (conventional [CT] and no-tillage [NT]) on the
      activity density and diversity of carabid beetles (Coleoptera: Carabidae) was
      studied by pitfall trapping within a rain-fed cropping system in northwestern
      Idaho, 2000-2002. The cropping rotation consisted of a spring cereal (barley,
      Hordeum vulgare L., in 2000 and 2001; and wheat, Triticum aestivum L., in 2002),
      spring dry pea (Pisum sativum L.) 2000-2002, and wheat (T. aestivum), spring in
      2000 and 2001, and winter in 2002. A total of 14,480 beetles comprised of 30
      species was captured, with five numerically dominant species [Poecilus scitulus
      L., Poecilus lucublandus Say, Microlestes linearis L., Pterostichus melanarius
      Ill., and Calosoma cancellatum (Eschscholtz)], accounting for 98% of all
      captures. All species including the dominants responded idiosyncratically to
      tillage regimen. Adjusting for trapping biases did not significantly change
      seasonal activity density of Poecilus spp. or Pt. melanarius to tillage. More
      beetles were captured in CT than in NT crops because of the dominance of P.
      scitulus in CT, whereas species richness and biological diversity were generally
      higher in NT crops. Observed patterns suggest that direct effects of tillage
      affected some species, whereas indirect effects related to habitat
      characteristics affected others. CT may provide habitat preferable to xerophilic
      spring breeders. A relationship was found between beetle species size and tillage
      regimen in pea and to a lesser extent across all spring crops, with large species
      (>14 mm) conserved more commonly in NT, small species (<7 mm) in CT, and
      intermediate species (7-14 mm) conserved equally between tillage systems.

PMID- 17445371
TI  - Predation and life table of Feltiella acarisuga (Diptera: Cecidomyiidae) preying
      on eggs of Tetranychus urticae (Acari: Tetranychidae).
AB  - Feltiella acarisuga (Vallot) is a common gall midge that feeds on many species of
      spider mites. Predation and all major biological and life table parameters of F.
      acarisuga were determined using eggs of the twospotted spider mite, Tetranychus
      urticae (Koch), as prey under laboratory conditions (26.7 degrees C, 85% RH, and
      14:10 [L:D] h). First-, second-, and third-instar F. acarisuga larvae consumed an
      average of 37.8, 60.4, and 87.2 T. urticae eggs per day, respectively. Larvae
      consumed a total of 185.4 eggs each from first to third instars, and female
      larvae consumed 201.2 spider mite eggs, 18.6% more than male larvae.
      Developmental time of F. acarisuga was 2.6, 7.8, and 7.0 d for eggs, larvae, and
      pupae, respectively, with an average of 17.4 d from oviposition to adult
      emergence. Female immatures developed slightly slower ( approximately 1 d) than
      males. Adult longevities of F. acarisuga averaged 13.0 d. After an average of 1.1
      d preoviposition period, each female laid an average of 33.3 eggs during her
      lifespan. The intrinsic rate of natural population increase (r), net reproductive
      rates (R(o)), gross reproductive rate (Sigmam(x)), generation time (T), doubling
      time (DT), and the finite rate of increase (lambda) of F. acarisuga were
      estimated by life table analysis at 0.1155/d, 15.25 eggs per female, 21.69 eggs
      per female, 23.6 d, 6.0 d, and 1.1225/d, respectively. Because the r value of F.
      acarisuga is relatively lower than that of T. urticae, frequent release of F.
      acarisuga may be necessary to suppress populations of T. urticae.

PMID- 17445372
TI  - Reproductive biology of Fidiobia dominica (Hymenoptera: Platygastridae), an egg
      parasitoid of Diaprepes abbreviatus (Coleoptera: Curculionidae).
AB  - The reproductive biology of Fidiobia dominica Evans (Hymenoptera: Platygastridae)
      was studied in the laboratory (25.6 +/- 1 degrees C) using host eggs of Diaprepes
      abbreviatus L. (Coleoptera: Curculionidae). F. dominica readily parasitized D.
      abbreviatus eggs on both host plant and wax paper substrates. The number of egg
      masses parasitized and the number of offspring produced were higher when females
      were offered more than one host egg mass but did not differ when either two or
      three egg masses were offered. Female parasitoids that were provided with host
      eggs and a honey food source lived significantly longer than those that were not
      provided a food source; however, they did not parasitize more D. abbreviatus
      eggs. Oviposition occurred in host eggs from 0 to 7 d old, and host mortality was
      relatively consistent for eggs 0-5 d old and lower for eggs 6-7 d old. Successful
      parasitoid emergence seldom occurred after host eggs were 4 d old, and by 7 d, no
      adults successfully emerged. Developmental time from egg to adult was 19.3 +/-
      0.2 d for males, significantly more rapid than the females (20.4 +/- 0.1 d). The
      mean longevity of adult females was 8.0 +/- 0.4 d, with a mean oviposition period
      of 2.7 +/- 0.3 d; males survived 8.1 +/- 0.4 d. The demographic parameters
      including intrinsic rate of increase (r(m)), generation time (T), and net
      reproduction (R(o)) were 0.142/d, 22 d, and 22.4 female eggs/d, respectively.

PMID- 17445373
TI  - Leaf extrafloral nectaries enhance biological control of a key economic pest,
      Grapholita molesta (Lepidoptera: Tortricidae), in peach (Rosales: Rosaceae).
AB  - Extrafloral nectaries (EFNs) in many plant species produce sugary secretions that
      commonly attract ants. This research determined the impact of peach (Prunus
      persica L. Batsch) EFNs on the biological control of the oriental fruit moth,
      Grapholita molesta (Busck) (Lepidoptera: Tortricidae), a key economic pest in
      peach orchards, and studied interactions of EFNs and ants. Studies (2002-2005) in
      peach orchards of the mid-Atlantic United States showed that 'Lovell' peach trees
      with EFNs supported more parasitic Hymenoptera in the spring and increased the
      parasitism of G. molesta larvae later in the season than those trees without
      EFNs. Ant exclusion experiments revealed that trees with EFNs harbored fewer G.
      molesta larvae when ants were permitted access to the tree canopies. Furthermore,
      the trees with EFNs had approximately 90% less fruit injury by G. molesta,
      indicating that EFNs have a protective role for the fruit as well. The results
      show that the combined actions of ants and parasitic Hymenoptera confer an EFN
      mediated protective effect spanning the whole fruit growing season. When EFNs are
      present, naturally occurring biological control agents can reduce damage by G.
      molesta in peach orchards without insecticide inputs. The EFNs are an important
      host-plant characteristic that should be retained in future peach cultivar
      selections as a means of enhancing biological control.

PMID- 17445374
TI  - Predation by adult and larval lady beetles (Coleoptera: Coccinellidae) on initial
      contact with lady beetle eggs.
AB  - Naive adults and larvae of the native lady beetles Coleomegilla maculata
      (DeGeer), Cycloneda munda (Say), Hippodamia convergens Guerin-Meneville, Olla v
      nigrum (Mulsant), and the exotic lady beetle Harmonia axyridis (Pallas)
      (Coleoptera: Coccinellidae) were tested for their initial response to eggs of
      these five lady beetle species and for egg consumption on first contact and after
      3 h. Additionally, field-collected O. v-nigrum and H. axyridis adults were
      tested. C. maculata, H. axyridis, and O. v-nigrum adults responded similarly to
      all egg species on first contact. Higher numbers of C. munda adults did not eat
      C. maculata, H. convergens, and O. v-nigrum eggs on first contact compared with
      numbers that did eat C. munda and H. axyridis eggs. H. convergens adults always
      ate C. munda eggs but hardly ate H. axyridis eggs on first contact. Results
      showed that over the 3-h interval, egg predation by those predators feeding on
      first contact was always higher, except for adults and larvae of C. maculata,
      than for those that did not feed on first contact. Thus, acceptance of eggs on
      initial contact does impact egg survival. It is likely that eggs of all native
      species tested (i.e., C. maculata, C. munda, H. convergens, and O. v-nigrum), but
      not exotic H. axyridis eggs, are suitable food for C. maculata, H. convergens,
      and O. v-nigrum, whereas only C. munda eggs serve as suitable food for C. munda.
      In direct contrast, all egg species tested would likely serve as suitable food
      for the exotic H. axyridis.

PMID- 17445375
TI  - Olfactory response of megachilid bees, Osmia lignaria, Megachile rotundata, and
      M. pugnata, to individual cues from old nest cavities.
AB  - The megachilid bees Osmia lignaria Say, Megachile rotundata (F.), and M. pugnata
      Say were tested for attraction to various components associated with their old
      nest cavities, or chemical extracts of these components, using a Y-tube olfactory
      response bioassay. Female bees of these species are known to nest in or near old
      nest cavities, implying that remnant nest components are important cues for bees
      looking for nest cavities. Significant results show that female bees were
      attracted to components that may provide species-specific cues or indicate
      conspecific nesting activity. Specifically, O. lignaria females showed attraction
      only to the female cocoon. M. rotundata females were attracted to intact nest
      cells, the fecal material on the outside of a cocoon, leaf pieces used as nest
      cell lining, and the extract of leaf pieces. M. pugnata females were attracted to
      the whole nest cell, the paper straw nesting material with attached cocoon, and
      feces.

PMID- 17445376
TI  - Hydrilla stems and tubers as hosts for three Bagous species: two introduced
      biological control agents (Bagous hydrillae and B. affinis) and one native
      species (B. restrictus).
AB  - Field observations suggested that the introduced Hydrilla verticillata (L.f.)
      Royle biological control agent, a stem weevil, Bagous hydrillae O'Brien, would
      feed on hydrilla tubers and stems, and a native species, Bagous restrictus
      LeConte, would feed on hydrilla stems. In choice tests, B. hydrillae readily
      oviposited in hydrilla tubers. Larval development of B. hydrillae in hydrilla
      tubers was similar to that in stems; greater adult biomass was attained and less
      time was needed to complete development when the larvae were fed tubers. Larvae
      of the hydrilla tuber weevil, B. affinis Hustache, did not complete development
      in hydrilla stems. Larvae of B. affinis completed development more rapidly when
      fed new compared with old hydrilla tubers. The native B. restrictus successfully
      completed development in hydrilla stems, although the larvae required slightly
      more time compared with the biocontrol agent, B. hydrillae. These findings
      indicated that feeding on tubers by B. hydrillae may benefit the species
      particularly when hydrilla stems are seasonably absent or unsuitable especially
      in more northern climates. In terms of hydrilla control, damage to tubers by this
      species constitutes a reduction in future infestations of hydrilla propagated by
      tubers. Finally, hydrilla is suitable to the native weevil, B. restrictus,
      because larvae completed development in hydrilla stems.

PMID- 17445377
TI  - Alfalfa living mulch advances biological control of soybean aphid.
AB  - Despite evidence for biological control in North America, outbreaks of the
      invasive soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), continue
      to occur on soybean (Glycine max L. Merr.). Our objectives were to determine
      whether natural enemies delay aphid establishment and limit subsequent population
      growth and whether biological control can be improved by altering the within
      field habitat. We hypothesized that a living mulch would increase the abundance
      of the aphidophagous community in soybean and suppress A. glycines establishment
      and population growth. We measured natural enemy and A. glycines abundance in
      soybean grown with and without an alfalfa (Medicago sativa L.) living mulch.
      Soybean grown with an alfalfa living mulch had 45% more natural enemies and
      experienced a delay in A. glycines establishment that resulted in lower peak
      populations. From our experiments, we concluded that the current natural enemy
      community in Iowa can delay A. glycines establishment, and an increase in
      aphidophagous predator abundance lowered the rate of A. glycines population
      growth preventing economic populations (i.e., below the current economic
      threshold) from occurring. Incorporation of a living mulch had an unexpected
      impact on A. glycines population growth, lowering the aphids' intrinsic rate of
      growth, thus providing a bottom-up suppression of A. glycines. We suggest future
      studies of living mulches or cover crops for A. glycines management should
      address both potential sources of suppression. Furthermore, our experience
      suggests that more consistent biological control of A. glycines may be possible
      with even partial resistance that slows but does not prevent reproduction.

PMID- 17445378
TI  - Influence of within-orchard trap placement on catch of codling moth (Lepidoptera:
      Tortricidae) in sex pheromone-treated orchards.
AB  - The influence of trap placement on catches of codling moth, Cydia pomonella L.,
      was examined in a series of studies conducted in orchards treated with Isomate-C
      Plus sex pheromone dispensers. Mark-recapture tests with sterilized moths
      released along the interface of pairs of treated and untreated apple and pear
      plots found that significantly more male but not female moths were recaptured on
      interception traps placed in the treated plots. In a second test, significantly
      higher numbers of wild male and female moths were caught on interception traps
      placed in treated versus untreated plots within a heavily infested orchard. The
      highest numbers of male moths were caught on traps placed along the interior edge
      of the treated plots. Trap position had no influence on the captures of female
      moths. In a third test, north-south transects of sex pheromone-baited traps were
      placed through adjacent treated and untreated plots that received a uniform
      release of sterilized moths. Traps on the upwind edge of the treated plots caught
      similar numbers of moths as traps upwind from the treated plots. Moth catch was
      significantly reduced at all other locations inside versus outside of the treated
      plots, including traps placed on the downwind edge of the treated plot. In a
      fourth test, five apple orchards were monitored with groups of sex pheromone
      baited traps placed either on the border or at three distances inside the
      orchards. The highest moth counts were in traps placed at the border, and the
      lowest moth counts were in traps placed 30 and 50 m from the border. In a fifth
      test, the proportion of traps failing to catch any moths despite the occurrence
      of local fruit injury was significantly higher in traps placed 50 versus 25 m
      from the border. The implications provided by these data for designing an
      effective monitoring program for codling moth in sex pheromone-treated orchards
      are discussed.

PMID- 17445379
TI  - Grassland composition affects season shifts in seed preference by Pogonomyrmex
      barbatus (Hymenoptera: Myrmicinae) in the Edwards Plateau, Texas.
AB  - The effects of season and community composition as generated by livestock
      herbivory of differing intensity on seed species preference by Pogonomyrmex
      barbatus (F. Smith) were studied in a semiarid savanna on the Edward's Plateau,
      TX. Seasonal differences in nutrient requirements of the colony could lead to
      differential preferences for seeds harvested in spring and fall. Field cafeteria
      studies were conducted to test the hypothesis that late successional species,
      with their high nutrient content, would be chosen regardless of grazing intensity
      or season. Commercial seeds of known nutrient content were used to test the
      hypothesis that high protein levels would be chosen in spring and high
      carbohydrate levels in the fall. Naturally occurring seeds were differentially
      harvested and some were preferred regardless of relative availability. Total seed
      harvest in cafeteria experiments was higher in spring than in fall. Commercial
      seeds were harvested equally among treatments within a season; thus, nutrient
      selection was indistinguishable. Preference for native species was significantly
      different in both seasons but was influenced by a significant interaction with
      grazing treatments. Bouteloua curtipendula, a late successional mid-grass, was
      harvested significantly more in the spring than the fall and at higher rates in
      the heavily grazed treatment, rejecting the hypothesis that they would be chosen
      regardless of treatment or season. Seed preference for late successional grasses
      within heavily grazed communities may slow succession after grazing. During
      disturbance recovery, late successional species may be reduced by forager
      preference and rates of spring harvest.

PMID- 17445380
TI  - Effect of microenvironment on development of a gall midge.
AB  - This study assessed the influence of microenvironment on the establishment and
      relative reproductive success of the gall-forming midge Rhopalomyia californica
      Felt on its host plant Baccharis pilularis De Candolle in Marin County, CA. Mesh
      cages were used to alter the microenvironment, which also allowed us to assess
      the validity of using these types of experimental manipulations in this system.
      Temperature, light intensity, wind speed, and stem growth were compared in caged
      and uncaged B. pilularis plots in two sites during three seasons. Cage presence
      significantly altered the microenvironment of R. californica but did not affect
      development. R. californica establishment was greater when growing on host plants
      with increased stem growth. Season had the largest impact on gall establishment
      and reproductive success, with the highest establishment and success rates in
      late winter to early spring, which correlated with the growing period of B.
      pilularis. These results suggest that the seasonality of R. californica
      reproductive success is linked to the phenology of its host plant. When the
      growing conditions for the plant are less than ideal, R. californica performance
      is stimulated by increased stem growth. Cage presence was not a significant
      driver of population dynamics because it did not change the environment in an
      ecologically meaningful way. We therefore assert that the use of cages for
      experimental manipulations in this study system does not alter R. californica
      performance.

PMID- 17445381
TI  - Susceptibility of native and non-native common reed to the non-native mealy plum
      aphid (Homoptera: Aphididae) in North America.
AB  - An aggressive, non-native haplotype (distinct genetic lineage within a species)
      of Phragmites australis is invading brackish and freshwater systems in the
      eastern United States, potentially displacing native haplotypes. We studied the
      differential susceptibility of native and non-native populations collected from
      sites throughout North America to the non-native aphid, Hyalopterus pruni. In a
      greenhouse study, we found significantly higher aphid populations on native
      haplotypes than on the non-native haplotype 2 mo after infestation. Aphid feeding
      caused chlorosis and death of native stems, and in some cases, killed whole
      native genets. The non-native plants remained relatively undamaged. In a field
      study, non-native plants had significantly lower aphid densities than native
      plants or remained aphid free. There was an interactive effect in which aphid
      populations increased on the native plants over the 1-mo study period but
      remained low on non-native plants over the same period. The susceptibility of
      native North American populations of P. australis to non-native aphid infestation
      may indirectly affect the ability of these native plants to compete with non
      native plant populations, ultimately contributing to the decline of native
      haplotypes.

PMID- 17445382
TI  - Quantitative differences in aphid virulence and foliar symptom development on
      tomato plants carrying the Mi resistance gene.
AB  - The Mi resistance gene in tomato reduces the feeding, fecundity, and survival of
      certain isolates of the potato aphid (Macrosiphum euphorbiae Thomas). This study
      compared the performance of two potato aphid isolates, WU11 and WU12, on nearly
      isogenic susceptible (Mi-) and resistant (Mi+) tomato cultivars. Although Mi
      significantly reduced the population growth of both aphids, WU12 numbers
      decreased by only 15% compared with 95% for isolate WU11. These results show that
      there are quantitative differences in virulence among potato aphid isolates.
      Compared with WU11 aphids, isolate WU12 caused more necrosis on both resistant
      and susceptible plants, and this increased damage may play a role in the partial
      virulence of isolate WU12. However, infestation with aphid isolate WU12 did not
      compromise plant defenses against isolate WU11 in resistant plants. Prior
      inoculation with either aphid isolate caused a modest reduction in the survival
      of WU12 adults, but this form of induced resistance was observed on both
      resistant and susceptible cultivars. Thus, Mi did not play a role in acquired
      resistance or mediate any indirect interactions between the two aphid isolates.
      Notably, the mode of action of Mi-mediated resistance seemed to differ depending
      on the aphid isolate tested. Mi dramatically deterred feeding by WU11 aphids,
      whereas the effects of resistance on isolate WU12 seemed to be caused primarily
      by antibiosis. Tolerance did not seem to be a major component of Mi-mediated
      responses, although resistant plants showed a modest reduction in the amount of
      foliar necrosis induced per aphid compared with susceptible plants.

PMID- 17445383
TI  - Host plant use in sympatric closely related flea beetles.
AB  - Studies on strategies of host plant use in sympatric-related species are
      significant to the theory of sympatric speciation. Altica fragariae Nakane and
      Altica koreana Ogloblin are sympatric closely related flea beetles found in
      Beijing, northern China. All their recorded host plants are in the subfamily
      Rosoideae of the Rosaceae, so we regard them as a model system to study
      interactions between herbivorous insects and plant-insect co-evolution. We
      conducted a set of experiments on the host preference and performance of these
      flea beetles to study whether these closely related species have the ability to
      use sympatric novel host plants and whether monophagous and oligophagous flea
      beetles use the same strategy in host plant use. Oviposition preference
      experiments showed that A. koreana, a monophagous flea beetle, displayed high
      host fidelity. However, A. fragariae, which is oligophagous, often made
      "oviposition mistakes," ovipositing on nonhost plants such as Potentilla
      chinensis, the host plant of A. koreana, although normal host plants were
      preferred over novel ones. Larval performance studies suggested that A. fragariae
      was able to develop successfully on P. chinensis. Feeding experiences of larvae
      had no effect on feeding preference, oviposition preference, and fecundity of
      adults. However, females were impaired in their reproductive ability when fed on
      nonhost plants. Therefore, A. fragariae finished their development of larval
      stages on P. chinensis and came back to their primary host plant, Duchesnea
      indica, for feeding and reproduction after eclosion.

PMID- 17445384
TI  - Temperature-mediated relationship between western flower thrips (Thysanoptera:
      Thripidae) and chrysanthemum.
AB  - Modeling the effect of temperature on the sustainability of insect-plant
      interactions requires assessment of both insect and plant performance. We
      examined the effect of temperature on western flower thrips, Frankliniella
      occidentalis (Pergande), a generalist herbivore with a high reproductive rate,
      and chrysanthemum inflorescences, a high quality but relatively fixed, ephemeral
      resource for thrips population growth. We hypothesized that different thrips
      versus plant responses to temperature result in significant statistical
      interaction of temperature with thrips abundance and flower damage attributes
      over time. Experiments were conducted at five temperatures between 20.7 and 35.3
      degrees C, with thrips infestation and time after infestation as main effects.
      Only minor, uncontrolled variations in relative humidity and light intensity may
      otherwise have influenced the results. High temperatures lead to an initially
      rapid increase in density of thrips followed by abrupt declines in abundance. The
      rate of floral senescence increased with temperature and thrips infestation, as
      indicated by a reduced fresh biomass and greater leaching of yellow pigments.
      Multiple regression indicated that indices of plant damage responded more
      directly to thrips density at low than high temperature, supporting the
      conclusion that temperature affected the outcome beyond what was predictable
      simply from differential plant and insect optima. The relative intensity of
      damage caused by individual thrips decreased with increasing temperature, likely
      caused by thrips competition and reduced survival, growth, and fecundity on
      depleted inflorescences. Reduced per capita damage at high temperature may be
      common in insects exploiting fixed plant resources that exhibit an accelerated
      rate of deterioration at high temperatures.

PMID- 17445385
TI  - Inheritance of female flight in Lymantria dispar (Lepidoptera: Lymantriidae).
AB  - A clinal female flight polymorphism exists in the gypsy moth, Lymantria dispar
      L., where female flight diminishes from east to west across Eurasia. A Russian
      population where females are capable of sustained ascending flight and a North
      American population with females incapable of flight were crossed: parentals,
      reciprocal F(1) hybrids, double reciprocal F(2) hybrids, and all possible
      backcrosses to both the parental lines were compared. Heritabilities were
      estimated using a threshold model, female offspring on female parent regressions,
      and joint-scaling analyses. Heritability of female flight capability measured
      using a free flight test was at least 0.60, and variation in wing size, muscle
      strength, and flight behaviors contributed to the flight polymorphism. Relative
      wing size varied continuously and had a heritability of 0.70. Environmental
      variation accounted for >90% of the variation in female preflight weight and
      relative flight muscle strength, as estimated by an inverted female's ability to
      right herself. Preflight walking behavior and early deposition of eggs were each
      inherited through a single gene with two co-dominant alleles. There was no
      evidence for sex-linkage or maternal effects in female flight capability or
      associated traits. Continued vigilance to exclude and eradicate introductions of
      strains capable of female flight in North America is warranted even in areas
      where no females fly, because some of the alleles needed for full flight
      capability may not be present in the North American populations, and some flight
      capability is maintained in the hybrids that could increase the rate of spread of
      L. dispar.

PMID- 17445398
TI  - [Chinese expert consensus document on angiotensin converting enzyme inhibitors in
      cardiovascular diseases].

PMID- 17445400
TI  - [Investigate the relation between atrial fibrillation and coronary heart disease
      in the elderly: an analysis of pathological data of 509 cases].
AB  - OBJECTIVE: To investigate the relation between atrial fibrillation (AF) and
      coronary heart disease according to the pathological data. METHOD: Total 540 out
      of 1012 anatomic older cases were admitted to our study, according to the
      clinical and pathological data in our hospital. RESULTS: (1) The incidence of AF
      increased significantly with aging (Cochran-Armitage trend test, P<0.01). (2) The
      AF patients were more likely to accompany coronary heart disease (P=0.0028) based
      on the anatomical documentation; the incidence of myocardial infarction in the AF
      group was statistically significant higher than that in the sinus rhythm group
      (P=0.0144). The level of coronary artery lesion in AF group was statistically
      significant severe than that in the sinus rhythm group. (3) Age (OR=1.34, 95% CI
      1.11 - 1.60), male (OR=5.71, 95% CI 1.87 - 17.39) and chronic heart failure
      (OR=1.87, 95% CI 1.27 - 2.76) were independent risk factors of AF based on
      multivariant logistic analysis, while coronary heart disease (OR=1.47, 95% CI
      0.91 - 2.39) was not an independent risk factor. CONCLUSIONS: The incidence of AF
      increases significantly with aging in the elderly. The AF patients seem more
      likely to accompany coronary heart disease but coronary heart disease may be not
      the independent risk factor of AF in the elderly.

PMID- 17445401
TI  - [Study on expression of mineralocorticoid receptor in human atria during atrial
      fibrillation].
AB  - OBJECTIVE: To investigate the mRNA and protein expression of mineralocorticoid
      receptor (MR) in patients with atrial fibrillation. METHODS: Twenty-five patients
      with rheumatic heart valve disease, 12 in sinus rhythm and 13 in chronic atrial
      fibrillation (>or= 6 months), underwent transthoracic echocardiography and right
      and left atrial lateral wall tissue samples were obtained from these patients
      during mitral/aortic valve replacement operation. Realtime quantitative PCR and
      Western blot were used to determine the mRNA and protein expression of MR in
      atria specimens. The distribution of MR in human atria was analyzed by specific
      immunohistochemical staining. RESULTS: The left atrial diameters increased
      markedly in atrial fibrillation group compared with that in sinus rhythm group
      (P<0.01). And the results showed that the level of mRNA and protein of MR were
      increased significantly in atrial fibrillation group compared with those in sinus
      rhythm group (P<0.01 or 0.05), whereas the expression of mRNA and protein of MR
      were found to be no difference between left atria and right atria both in
      fibrillation and sinus groups (all P>0.05). The special immunohistochemical
      staining demonstrated that MR was abundant in the human atrial myocardium and MRs
      were located mainly in the cytoplasm of atrial cells, which were more evident in
      atrial fibrillation group than those in sinus rhythm group. CONCLUSION: These
      findings suggested that MRs were upregulated in atrial fibrillation and
      aldosterone antagonists may be effective in treating atrial fibrillation.

PMID- 17445402
TI  - [Electrophysiological findings and ablation strategies in patients with atrial
      tachyarrhythmias after left atrial circumferential ablation in the treatment of
      atrial fibrillation].
AB  - OBJECTIVE: To report the electrophysiological findings and the ablation
      strategies in patients with atrial tachyarrhythmias (ATAs) or atrial fibrillation
      (AF) recurrence after left atrial circumferential ablation (LACA) in the
      treatment of AF. METHODS: 91 patients with AF had LACA procedure from April 2004
      to May 2006, 19 of which accepted the second ablation procedure due to ATAs or AF
      recurrence. In all the 19 patients [17 male, 2 female, age 25 - 65 (53 +/- 12)
      years], 11 presented with paroxysmal AF before the first ablation procedure, 2
      with persistent AF and 6 with permanent AF. Pulmonary vein potentials (PVP) were
      investigated in both sides in all the patients. RESULTS: Delayed PVP was
      identified inside the left circular line in 5 patients, in the right in 1 and
      both in 2 during sinus rhythm. "Gap" conduction was found and successfully closed
      guided by circular mapping catheter. In 3 cases, irregular left atrial
      tachycardia was caused by fibrillation rhythm inside the left ring via
      decremental "gap" conduction. Reisolation was done successfully again guided by 3
      D mapping and made the left atrium in sinus rhythm but the fibrillation rhythm
      was still inside the left ring. Pulmonary vein tachycardia with 1:1 conduction to
      the left atrium presented in one case and reisolation stopped the tachycardia. No
      PVP was discovered in both sides in 4 patients but other tachycardias could be
      induced, including two right atrial scar related tachycardias, two
      supraventricular tachycardias mediated by concealed accessory pathway, one cavo
      tricuspid isthmus dependent atrial flutter and one focal atrial tachycardia near
      the coronary sinus ostium. All the tachycardias in these 4 patients were
      successfully ablated with the help of routine and 3-D mapping techniques. In the
      rest 3, which were in AF rhythm, LACA was successfully done again. After a mean
      follow-up of 4 - 26 (11.5 +/- 8.5) months, 16 patients were symptom free without
      anti-arrhythmic drug therapy; 1 of them had frequent palpitation attack with
      Holter recording of atrial premature contractions; 2 of them with permanent AF
      became paroxysmal in one, and still in AF in the other. CONCLUSIONS: Reconduction
      between the left atrium and the pulmonary veins is the dominant factor for post
      LACA ATAs and AF recurrence. Other forms of atrial tachycardias or
      supraventricular tachycardias may coexist with AF or sometimes trigger AF. LACA
      can not sufficiently modify AF substrate in some permanent AF patients.

PMID- 17445403
TI  - [Ablation of the orifices of the pulmonary veins under direct vision by using the
      transballoon ultrasound ablation catheter for permanent atrial fibrillation with
      rheumatic valve disease].
AB  - OBJECTIVE: To evaluate the effect and possibility of surgical ablation of the
      pulmonary vein orifices under direct vision with transballoon ultrasound ablation
      catheter for patients with permanent atrial fibrillation and rheumatic valve
      disease. METHODS: 21 consecutive patients with rheumatic valve disease and
      permanent atrial fibrillation undergoing mitral valve replacement surgery were
      enrolled for this study from December 2002 to September 2003. All the cases were
      divided into 2 groups by whether or not receiving an additive pulmonary vein
      ablation procedure. The test group [6 male, 5 female, aged (51.55 +/- 7.83)
      years, atrial fibrillation duration (5.50 +/- 5.40) years, left atrial diameter
      (7.27 +/- 1.39) cm, LVEF (53.95 +/- 4.54)% and NYHA class II - IV] undertook a
      surgical isolation of the pulmonary vein orifices by using a transballoon
      ultrasound ablation catheter addition to routine mitral valve replacement. The
      control group [3 male, 7 female, aged (53.30 +/- 7.86) years, atrial fibrillation
      duration (4.50 +/- 3.47) years, left atrial diameter (6.74 +/- 0.62) cm, LVEF
      (56.91 +/- 3.78)% and NYHA class II - IV] received the valve replacement surgery
      alone. RESULTS: There were not any complications in both groups. With an
      electrical cardioversion 3 months after the surgery, 73% patients in the
      ultrasound ablation group were free from AF over 1 year while only 10% patients
      in control group (P=0.003). During an average follow-up duration of (45.92 +/-
      4.61) months, 63.6% were in sinus rhythm in ultrasound ablation group while none
      in the control group. Left atrial volume decreased significantly at 1 year after
      surgery compared to that at 3 months after surgery in the test group [(97.83 +/-
      32.39) cm(3) vs. (150.78 +/- 52.32) cm(3), P<0.05], and the end systolic diameter
      (LAESD) and end diastolic diameter (LAEDD) also decreased [(4.12 +/- 0.39) cm vs.
      (5.09 +/- 0.98) cm, P<0.05, respectively], while there were no apparently changes
      in the control group. CONCLUSIONS: Ablation of the orifices of the pulmonary
      veins under direct vision with transballoon ultrasound ablation catheter during
      mitral valve surgery seems effective to maintain sinus rhythm after electrical
      cardioversion and could be performed safely. The function of left atrial and
      cardiac output improved during long term follow-up of 46 months.

PMID- 17445404
TI  - [Left atrial size and function after radiofrequency catheter ablation for
      paroxysmal atrial fibrillation].
AB  - OBJECTIVE: To evaluate the impact of radiofrequency catheter ablation on left
      atrial (LA) size and function in patients with paroxysmal atrial fibrillation
      (PAF) and whether there is any difference between segmental pulmonary vein ostial
      isolation (SPVI) and circumferential pulmonary vein ablation (CPVA). METHODS:
      Sixty-six patients with highly symptomatic atrial fibrillation were assigned to
      undergo either SPVI or CPVA. Transthorax echocardiography was performed before, 1
      day, 1 months and 3 months after the procedure. LA dimension, LA area, late
      diastolic peak velocity of mitral valve inflow (A) and peak atrial systolic
      mitral annulus velocity (A') were recorded. RESULTS: Of 66 consecutive patients
      with symptomatic PAF, 30 patients underwent SPVI and 36 underwent CPVA. After a
      mean follow-up of (315 +/- 153) days, 21 patients (70%) after SPVI and 28
      patients (75%) after CPVA were free of atrial tachyarrhythmia. As compared with
      the baseline, LA area decreased at 1-month after ablation in SPVI group and at 3
      month in CPVA group. LA dimension decreased also in SPVI group, but did not in
      CPVA group. A velocity and A' velocity declined remarkably 1 day after CPVA, and
      restored 3 months later. The former went back to the level of baseline, and the
      latter exceeded it apparently. In SPVI group, A velocity increased at 1-month,
      and maintained in 3-month after ablation. A' velocity increased at 3-month after
      ablation. No reduction of A velocity or A' velocity was found after SPVI.
      CONCLUSIONS: This study demonstrated a decrease in LA area and an improvement in
      LA systolic function 3 months after ablation for PAF. The LA damage by CPVA was
      more than that by SPVI, which was characterized by the reduction of LA function 1
      day after procedure and the delayed improvement of LA size and functional
      parameters.

PMID- 17445406
TI  - [Calpain I inhibition prevents pacing-induced structural remodeling for atrial
      fibrillation in canine].
AB  - OBJECTIVE: To study the relation of the structural remodeling processes and
      activation of calpain I. METHODS: Fifteen dogs were randomly divided into three
      groups. The dogs in pacing group (n=5) and inhibitor group (n=5) were subjected
      to 3 weeks of rapid atrial pacing at 600 beats/min, control dogs (n=5) were in
      sham-operated group. The dogs in inhibitor group were administered intravenous N
      Acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, and in pacing group and sham
      operated group were administered intravenous DMSO. The activity of calpain I was
      measured by hydrolyzing Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin. The
      ultrastructure of atrium was examined by light and electron microscopy. TnT
      expression was assessed by Western blot. Echocardiography examination was
      performed in all the three groups. RESULTS: Calpain I activity was significantly
      increased in pacing group (2.3-fold, P<0.01), and decreased in inhibitor group
      (1.1-fold, P>0.05), compared to sham-operated group respectively. The percentages
      of myolysis were (76.7 +/- 5.9)% and (20.8 +/- 8.1)% in pacing group and
      inhibitor group respectively (P<0.01). TnT expression decreased in the rapid
      pacing-induced persistent atrial fibrillation, and these effects were inhibited
      by calpain I inhibitor ALLM. The area and volume of left atrium tended to
      increase after 3 weeks ALLM treatment in inhibitor group, but the change was not
      as prominent as in pacing group (P<0.05). CONCLUSIONS: ALLM can decrease calpain
      I activity, and prevent canine atrial cardiomyocyte structural remodeling during
      atrial fibrillation. This study provided a capacity of atrial cardiomyocyte
      protection.

PMID- 17445407
TI  - [Atrial electrical, contractile and structural remodeling induced by short-term
      atrial tachycardia in a canine model].
AB  - OBJECTIVE: To evaluate atrial remodeling induced by short term pacing in a canine
      model. METHODS: Transvenous lead was inserted into the right atrial appendage of
      anesthetized mongrel dogs and paced for 5 hours at 450 bpm (n=12). Effective
      refractory period (ERP) and P-wave duration were measured before and post pacing
      and left ventricular pressure was monitored during the procedure.
      Echocardiography was performed to observe the presence or absence of spontaneous
      echo contrast and to assess the effect of rapid atrial pacing on atrial function.
      All measurements were obtained in sinus rhythm. Histology of the myocardium in
      left atrial trabeculae and appendages was examined by electron microscopy.
      RESULTS: Compared to pre-pacing status, ERP was significantly reduced [(87.27 +/-
      16.35) ms vs. (113.27 +/- 11.99) ms, P<0.01] at a cycle length of 300 ms, P-wave
      duration significantly increased [(56.09 +/- 8.62) ms vs. (52.09 +/- 7.63) ms,
      P<0.01], the peak velocity of atrial contraction significantly decreased [(48.92
      +/- 10.80) cm/s vs. (59.25 +/- 9.37) cm/s, P<0.05] while heart rates and left
      ventricular pressure were not affected post five hours rapid atrial pacing.
      Pacing also induced significantly cellular ultrastructures changes including
      myofibrils loss, glycogen accumulation, mitochondria loss and swelling.
      CONCLUSION: Short term pacing resulted in atrial electrical, contractile and
      structural remodeling.

PMID- 17445409
TI  - [Functional expression of congenital long QT syndrome related HERG mutation A561V
      in vitro].
AB  - OBJECTIVE: To investigate the functional expression of HERG mutation A561V
      detected in a Chinese congenital long QT syndrome family. METHODS: The mutation
      gene A561V was cloned into eukaryotic expressive vector pcDNA3 by quick site
      directed mutagenesis PCR and restriction enzymes. The wild-type HERG,
      heterozygous type HERG and HERG mutation A561V were respectively cotransfected
      with pRK5-GFP into HEK293 cells by Suprefact transfection regent. The protein
      expression was measured by immunofluorescence method and Western blot. The
      electrophysiological characteristics of transfected cells were determined by
      whole cell patch-clamp technique. RESULTS: Direct sequence analyses revealed a C
      to T transition at position 1682. A561V mutation was correctly combined to
      eukaryotic expressive vector pcDNA3 and expressed in HEK293 cells. The protein
      expression of mutation and heterozygosis were located in cytoplasm and cellular
      membrane. 155 kDa and 135 kDa protein bands were detected in wild type HERG
      channel while only 135 kDa protein band was shown in heterozygous and mutational
      channels. Significant HERG tail-current was recorded in wild type HERG channel
      but not in mutation and heterozygosis channels. CONCLUSION: This study evidenced
      a functional dominant-negative current suppression in HEK293 cells transfected
      with HERG mutation A561V.

PMID- 17445410
TI  - [Report on initiating clinical research for electrical and mechanical synchronism
      of selective region pacing in the right ventricular].
AB  - OBJECTIVE: To verify the electric synchronism, mechanic synchronism and
      hemodynamics of selective site pacing. METHODS: Pacing in the right ventricular
      cardiac apex (RVA), the right ventricular His bundle region (His), and the septum
      of right ventricular high-positioned outflow tract (RVOT), CO and CI were
      recorded. The electrical synchronism was assessed by observing the width and
      shape in a 12-lead surface ECG. The mechanical synchronism was estimated by using
      the VVI (vector velocity imaging) technology of the Acuson Sequia 512. RESULTS:
      The results showed that CO and CI were lower while pacing in RVA, but they were
      not significant different (P>0.05). The QRS width: (124 +/- 5.3) ms while pacing
      in His, (144 +/- 7.1) ms while pacing in RVOT and (156 +/- 8.6) ms while pacing
      in RVA. The QRS width while pacing in His and in RVOT were narrower than in RVA
      and there were significant differences (P<0.01). Vector velocity imaging showed
      that mechanical synchronism was better while pacing in RVOT than that in RVA.
      CONCLUSION: Pacing in RVOT seems better than pacing in traditional RVA, and the
      operation was no more difficult than the traditional operation.

PMID- 17445411
TI  - [Transvenous extraction of a broken permanent pacemaker lead which broken ends
      adhered to right ventricle].

PMID- 17445412
TI  - [Efficacy of intravenous Acehytisine Hydrochloride versus propafenone on
      terminating paroxysmal supraventricular tachycardia: a double-blinded, randomized
      multi-center study].
AB  - OBJECTIVE: In this double-blinded, randomized, parallel study, we investigated
      the clinical efficacy of intravenous Acehytisine Hydrochloride (AHH) and
      propafenone on terminating paroxysmal supraventricular tachycardia (PSVT).
      METHODS: Patients (18 - 70 years old) with either spontaneous or induced
      sustained supraventricular tachycardia lasted at least 15 min were recruited in
      this study. Exclusion criteria included sick sinus syndrome, atrial ventricular
      block or intraventricular block, etc. Eligible patients were randomly assigned to
      receive intravenously AHH (n=101) or propafenone (n=100) according to a
      proportion of 1:1 in a double-blinded manner. AHH (4 mg/kg, iv.) or propafenone
      (PRO, 1 mg/kg, iv.) was administered in 5 min followed by the same dose if no
      response was observed. Conversion times, vital signs, electrocardiograms were
      documented before and after drug administration. RESULTS: Except for age, the
      demographic characteristics and clinical features were comparable between the two
      groups. Efficacy on PSVT termination was comparable between AHH (72/101, 71.3%)
      and PRO group (73/100, 73.0%, P=0.6368). The average time from drug
      administration to conversion was also similar [AHH: (9.62 +/- 8.39) min vs. PRO:
      (10.61 +/- 9.47) min, P=0.5035]. In the AHH group, 59/72 episodes of PSVT were
      terminated by the first dose, and 66/72 were terminated prematurely. The average
      AHH dose in the 72 converted patients was (273.7 +/- 111.2) mg. In the PRO group,
      54/73 episodes of PSVT were terminated by the first dose. The
      electrocardiographic parameters, such as sinus recovery time, longest PP and RR
      interval, PR interval, QRS interval, QT interval after conversion were similar
      between the two groups. Transient adverse events were reported in 11/101 (10.9%)
      patients in the AHH group and in 18/100 (18.0%,) in the PRO group (P=0.1653).
      CONCLUSION: With the dosage used in the present study, the efficacy on
      terminating PSVT was comparable between AHH and PRO.

PMID- 17445413
TI  - [Relationship between abdominal obesity and left ventricular weight/function].
AB  - OBJECTIVE: To observe the relationship between abdominal obesity and left
      ventricular weight/function. METHODS: A total of 495 patients [265 males, mean
      age (55 +/- 12) years] with hypertension (139), diabetes (65), metabolic syndrome
      (285), diabetes complicated with hypertension (11) were enrolled in this study.
      Visceral adipose area (VA), the subcutaneous adipose (SA), the total abdominal
      adipose (TA) were measured by computerized tomography (CT) and left ventricular
      weight and function were obtained by echocardiography. Patients were divided into
      three groups according to the VA (I. VA<75 cm(2), n=173, II. VA>75 and < 110
      cm(2), n=153, III. VA >or= 110 cm(2), n=169). RESULTS: Left ventricular mass
      (LVM) and LVM index (LVMI) increased and LVEF and E/A decreased in proportion to
      increasing VA. Left ventricular hypertrophy (LVH) rate was significantly higher
      in group II and III compared to group I and LVEF was significantly reduced in
      group III compared to group I and II. There are significant correlation between
      LVMI and VA, SA, TA as well as between LVEF and VA after adjusting gender, age
      and blood pressure. Logistic regression analysis showed that VA is an independent
      predictor for LVH. CONCLUSION: The abdominal adipose accumulation is closely
      related to the left ventricular weight and function.

PMID- 17445414
TI  - [Risk factors for coronary artery disease stimulate urokinase receptor expression
      on monocytes].
AB  - OBJECTIVE: To evaluate the effect of risk factors for coronary artery disease
      (CAD) on urokinase receptor (uPAR) expression on monocytes. METHODS: A total of
      106 patients were enrolled and divided into five risk-factor groups: sixteen with
      hypertension, twenty-four with dyslipidemia, eighteen with hypertension +
      obesity, eighteen with dyslipidemia + obesity and thirty with hypertension +
      dyslipidemia + obesity. Seventeen healthy volunteers were recruited as control
      group. Monocyte expression of uPAR and mean fluorescence intensity index (MFI
      Index) of uPAR were measured by flow cytometer (FACSCalibur). RESULTS: No
      difference in monocyte uPAR expression was detected between hypertension and
      control group [(4.9 +/- 12.5)% vs. (7.7 +/- 10.3)%, P=0.74]. However, the uPAR
      expression was raised to (23.7 +/- 22.5)% in hyperlipidemia group, a 3.9- and a
      2.1-fold increase compared with those in hypertension (P<0.01) and control group
      (P<0.05), respectively. When combined with obesity, uPAR expression was elevated
      further to (32.9 +/- 30.8)% in hypertension + obesity group, (37.4 +/- 31.4)% in
      dyslipidemia + obesity group and (23.8 +/- 20.5)% in hypertension + dyslipidemia
      + obesity group, all having statistical significance compared with control group
      or hypertension group (P<0.01). The results were the same when corrected by age,
      BMI and hs-CRP. uPAR MFI Index was increased from 0.78 +/- 0.86 in control group
      to 1.91 +/- 1.97 and 3.33 +/- 2.52 in dyslipidemia group and hypertension +
      obesity group, respectively, P<0.05. Linear regression analysis revealed a
      significant correlation between uPAR expression and FBG concentration in
      dyslipidemia group, r=0.72, P=0.04. CONCLUSIONS: uPAR expression was elevated on
      monocytes in patients with risk factors for CAD. Dyslipidemia and obesity may
      contribute to the increase of uPAR expression.

PMID- 17445415
TI  - [Reperfusion arrhythmias in acute myocardial infarction do not enhance myocardial
      injury].
AB  - OBJECTIVE: To investigate the clinical implications of reperfusion arrhythmias
      during primary percutaneous coronary intervention (PCI) for patients with acute
      myocardial infarction (AMI). METHODS: Data from 228 AMI patients in whom the
      infarct-related artery (IRA) were successfully recanalized by primary PCI were
      retrospectively analyzed. The 228 patients were divided into 2 groups: myocardial
      ischemia-reperfusion injury (MIRI) group (n=119) in whom MIRI events occurred
      within minutes after successful recanalization of IRA, and non-MIRI group
      (n=109). The 119 patients in MIRI group were further divided into 3 subgroups:
      severe bradycardia with hypotension (brady-arrhythmia subgroup), lethal
      ventricular arrhythmias requiring electrical cardioversion (tachy-arrhythmia
      subgroup), and IRA antegrade flow less than or equal to TIMI 2 grade without
      angiographic evidence of abrupt closure (no-reflow subgroup). RESULTS: (1)
      Clinical and angiographic data: Compared with non-MIRI group, MIRI group was
      characterized by more inferior infarct location, shorter ischemic duration, more
      frequently right coronary artery as IRA, more diseased vessels, more often TIMI 0
      grade of initial antegrade flow in IRA, less pre-infarction angina, more renal
      insufficiency, and higher in-hospital mortality (13.4% vs. 4.6%, P=0.021). (2)
      The peak CK level was remarkably lower in brady-arrhythmia subgroup than that in
      non-MIRI group (2010 IU/L vs. 2521 IU/L, P=0.039). The peak CK or CK-MB level was
      notably higher in no-reflow subgroup than in non-MIRI group (4573 IU/L, 338 IU/L,
      respectively, P=0.000). (3) Left ventricular ejection fraction in no-reflow
      subgroup was significantly lower than in non-MIRI group (38.7% +/- 8.3% vs. 51.2%
      +/- 8.1%, P=0.000), left ventricular end-diastolic volume in no-reflow subgroup
      was greater than that in tachy-arrhythmia subgroup [(135 +/- 32) ml vs. (105 +/-
      19) ml, P=0.029]. CONCLUSION: Reperfusion arrhythmias may imply the existence of
      much survived myocardium and do not enhance myocardial damage, while no-reflow
      increases myocardial injury and induces permanent impairment of cardiac function.

PMID- 17445416
TI  - [CT features and anatomic-pathologic basis of the 16-slice spiral CT for aortic
      dissection].
AB  - OBJECTIVE: To determine the CT features and anatomic-pathologic basis of the 16
      slice Spiral CT (SCT) for aortic dissection (AD). METHODS: Forty-two cases with
      typical aortic dissection (AD) and 12 cases with intramural hematoma (IMH)
      underwent 16-slice SCT, performed with unenhanced, contrast-enhanced scanning and
      three-dimensional reconstruction. More attention was put on the true and false
      lumen, intimal flap, the entry tear and the involvement of branches of AD.
      RESULTS: (1) True and false lumen and intimal flap of AD could be shown in all of
      42 cases (100%), the entry tears were revealed in 41 cases (97.6%), and the true
      and false lumen and intimal flap extended spirally in 41 cases (97.6%). (2) For
      intramural hematoma (IMH), unenhanced CT depicted crescent-shaped areas with high
      attenuation extending along the walls of the aorta in 10 cases (83.3%), and low
      attenuation in 2 cases (16.7%), while contrast-enhanced CT showed no enhancement
      of attenuation in the crescent-shaped areas in all 12 cases. Nine cases (75%) of
      IMH were associated with penetrating aortic ulcer. CONCLUSIONS: The axial and
      three-dimensional images of 16-slice SCT can fast and exactly reveal the
      pathological and anatomical features of AD, and provide detailed imaging
      information for clinical therapy. It's very important for the selection of
      treatment methods.

PMID- 17445417
TI  - [oxLDL reduced endothelial progenitor cells survival and function via regulating
      Akt/eNOS signal pathway].
AB  - OBJECTIVE: To investigate the association between Akt/eNOS signal pathway changes
      and the survival/function of endothelial progenitor cells (EPC) in the presence
      of oxLDL, L-NAME or triciribine. METHODS: After 14 d culture, EPC was stimulated
      with different concentrations of oxLDL, L-NAME or triciribine for 48 h. In one
      group, EPC was preincubated with L-arginine for 24 h and then exposed to 50
      microg/ml oxLDL for 48 h. The survival and the ability of adhesion, migration and
      tube structure formation of EPC were observed and the level of phosphorylated Akt
      protein expression, eNOS protein and mRNA expression were assayed. RESULTS:
      Incubation with oxLDL at concentration 25 microg/ml or higher resulted EPC
      apoptosis, significantly reduced migratory rate, reduced adhesion to fibronectin
      and impaired ability of EPC to form tube structure in a dose-dependent manner. A
      simultaneous dose-dependent NO generation and Akt phosphorylation decrease as
      well as eNOS expression reduction at protein and mRNA levels were also observed.
      Pretreatment of EPC with L-arginine could attenuate these changes. CONCLUSION:
      oxLDL reduced EPC survival and function via regulating Akt/eNOS signal pathway.

PMID- 17445418
TI  - [Noninvasive detection of experimental vulnerable atherosclerotic plaques with
      99Tc m labeled C2A domain of synaptotagmin I].
AB  - OBJECTIVE: (99)Tc(m) labeled C2A domain of synaptotagmin I ((99)Tc(m)-Syt I-C2A)
      is used for noninvasive detection of vulnerable atherosclerotic plaque. METHODS:
      Recombinant C2A domain of synaptotagmin I, overexpressed in E. Coli, was
      thiolated with 2-iminothiolane (2-IT) and labeled with (99)Tc(m). Atherosclerotic
      plaques were produced in 5 rabbits by deendothelialization of the abdominal aorta
      and the rabbits were fed with cholesterol diet for 3 months. Three rabbits not
      manipulated served as normal controls. All animals were injected with (99)Tc(m)
      Syt I-C2A and underwent in vivo imaging thereafter. Aortas were then explanted
      for ex vivo imaging and histological characterization. RESULTS: In
      deendothelialized animals, intense radio-uptake in abdominal aorta, showed by
      gamma camera at 2 h after injection, was visualized and T/B was 3.25 +/- 0.51 by
      ROI measurement, quantitative uptake ratio of abdominal aortas with
      atherosclerotic lesions to thoracic aortas was 8.39 +/- 1.74 in ex vivo imaging.
      The mean uptake in specimens of abdominal aortas with lesions was 12.6-fold
      higher than in control abdominal aortas, and 10.2-fold higher than in thoracic
      aortas of deendothelialized animals by gamma-counter. CONCLUSION: (99)Tc(m)-Syt I
      C2A has a high affinity for vulnerable atherosclerotic plaque and is a suitable a
      gent for the noninvasive detection of vulnerable atherosclerotic plaque.

PMID- 17445419
TI  - [The effects of various beta-blockers on myocardial gap junction structure in rat
      with myocardial ischemia-reperfusion injury].
AB  - OBJECTIVE: To compare the effects of carvedilol, metoprolol and propranolol on
      myocardial gap junction (GJ) structure in rat with myocardial ischemia and
      reperfusion injury. METHODS: Rats were divided randomly into five groups: sham
      operation group (SO), myocardial ischemia and reperfusion group (IR), IR +
      carvedilol group (CV), IR + metoprolol group (MT), and IR + propranolol group
      (PP). The left anterior descending branch was ligated for 30 minutes and
      reperfused for 4 hours (IR). After 4 h reperfusion, the distribution and
      composition of gap junctional connexin 43 (CX43) were observed by
      immunofluorescence and laser scanning confocal microscopy (LSCM), and the
      quantification of CX43 was measured by LSCM. RESULT: Compared with SO group, IR
      resulted in abnormal distribution and composition of CX43-GJ and the impairment
      of CX43-GJ was significantly attenuated by CV, MT and PP treatments with the best
      effect observed in CV group (P<0.05 vs. MT and PP). CONCLUSION: These results
      suggest that beta-blockers, especially, carvedilol, could significantly attenuate
      IR induced CX43-GJ impairment.

PMID- 17445421
TI  - [Myocardial injury syndrome post radioablation in a patient with idiopathic
      ventricular tachycardia].

PMID- 17445422
TI  - [Transcatheter closure of recurrent patent ductus arteriosus after surgical
      ligation with double Amplatzer occluders].

PMID- 17445424
TI  - [Calling for further clinical studies on gastro-esophageal reflux disease in
      China].

PMID- 17445426
TI  - [No more misunderstandings in ulcerative colitis].

PMID- 17445428
TI  - [The changes of esophageal epithelial intercellular spaces before and after
      omeprazole treatment in erosive esophagitis].
AB  - OBJECTIVE: To observe the changes of ultra-micro structure of esophageal
      epithelium in patients with erosive esophagitis before and after omeprazole
      treatment. METHODS: 20 patients with erosive esophagitis diagnosed with
      gastroscopy were enrolled. All of them were treated with omeprazole (20 mg, 2/d)
      for 4 weeks, then underwent gastroscopy again. Biopsies were taken from 2 cm
      above Z-line. All the patients completed the questionnaire about reflux symptoms
      before and after the treatment. RESULTS: Before the treatment the mean, maximal
      and minimal intercellular spaces of esophageal epithelium were (1.14+/-0.15)
      microm, (1.47+/-0.15) microm and (0.85+/-0.17) microm respectively; after the
      treatment the mean, maximal and minimal intercellular spaces of esophageal
      epithelium were (0.51+/-0.18) microm, (0.72+/-0.25) microm, (0.36+/-0.15) microm
      respectively, with significant differences before and after the treatment
      (P=0.000). CONCLUSION: The dilated intercellular spaces of esophageal epithelium
      in erosive esophagitis patients can be recovered after a short time treatment of
      proton pump inhibitors.

PMID- 17445429
TI  - [An analysis of the DNA fingerprinting of intestinal flora in inflammatory bowel
      disease].
AB  - OBJECTIVE: DNA fingerprinting for inflammatory bowel disease (IBD) patients and
      healthy subjects was carried out to compare the difference of intestinal flora
      between the two groups. METHODS: DNA fingerprinting for IBD patients and healthy
      persons was set up with enterobacterial repetitive intergenic consensus (ERIC
      PCR) technology and the difference of intestinal flora between the two groups
      compared. RESULTS: DNA fingerprinting of the IBD patients and healthy subjects
      was identified and a significant difference was noticed between them. There were
      lots of bands in the DNA fingerprinting of the healthy subjects but few in that
      of the IBD patients. Strikingly, same distribution of the principal band of DNA
      fingerprinting was noticed in IBD patients. CONCLUSIONS: The variety of
      intestinal flora in healthy subjects is more apparent than that in IBD patients.
      An unique principal band might be the sequence of the presence of specific
      etiopathogenetic bacterium, or it might be the combined sequence of mixed
      bacterial flora.

PMID- 17445430
TI  - [An epidemiologic study of irritable bowel syndrome among adolescents in China].
AB  - OBJECTIVE: To explore the prevalence of irritable bowel syndrome (IBS) and its
      distribution characteristics among adolescents in China. METHODS: A stratified
      and randomized study by cluster sampling was employed, the study recruited 51 956
      students from high and primary schools in different Chinese cities. All students
      were requested to fill in a questionnaire. RESULTS: The prevalence of IBS in
      China was 53.5% according to the Manning criterion and 20.2% according to the
      Rome II criterion. The prevalence in male and female students showed no
      significant difference (P>0.05), but there was higher prevalence of IBS in high
      school students. The prevalence of IBS was 53.3% according to the Manning
      criterion and 19.6% according to the Rome II criterion in south China. The
      prevalence of IBS was 51.2% according to the Manning criterion and 18.9%
      according to the Rome II criterion in North China. The prevalence of IBS was
      58.0% according to the Manning criterion and 23.4% according to the Rome II
      criterion in west China. CONCLUSION: IBS is a common disorder among the
      adolescents and the prevalence of IBS is increasing with increase of age in
      adolescents.

PMID- 17445431
TI  - [The association between DPYD gene polymorphism and chemotherapeutic toxicity of
      5-FU in gastric carcinoma and colonic carcinoma].
AB  - OBJECTIVE: To explore the relationship between dihydropyrimidine dehydrogenase
      (DPYD) gene polymorphism and metabolism as well as chemotherapeutic toxicity of 5
      FU in gastric and colonic carcinoma. METHODS: Chemotherapy scheme based on 5-FU
      was used for the treatment of 75 patients with gastrointestinal carcinoma. Serum
      drug concentration and DPYD gene polymorphism (DPYD*2, *3, *4, *5, *9, *12) were
      detected with high performance liquid chromatography (HPLC) and gene chip
      technique respectively. RESULTS: It was found that there was no DPYD*2, *3, *4,
      *12 type mutation in all the patients. Of the DPYD*9 gene polymorphism loci in
      the 75 patients, there were 7 with heterozygote (9.3%) and 68 with wide type
      (90.7%). Of the DPYD*5 gene polymorphism loci in the 75 patients, there were 11
      with mutation (14.67%) and 23 heterozygote (30.67%) and 41 with wide type
      (54.67%). Ke value of DPYD*5 mutation was statistically lower than that of wild
      type (P=0.022). The incidence of middle-severe nausea and vomiting and white
      blood cell decrease in DPYD*5 gene type could be arranged from the highest to
      lowest as follows: mutation, heterozygote, wide type (P<0.05). The incidence of
      middle-severe nausea and vomiting was significantly higher in DPYD*9 heterozygous
      genotype than in DPYD*9 wild genotype (P<0.05). CONCLUSION: DPYD*5 gene mutation
      contributes to reduced DPYD enzyme activity and 5-FU dyes metabolism, which is
      associated with accumulation of 5-FU and chemotherapeutic toxicity in patients
      with gastric and colonic carcinoma.

PMID- 17445434
TI  - [The impact of right ventricular dysfunction on the clinical outcome of
      normotensive patients with pulmonary embolism].
AB  - OBJECTIVE: To investigate the prevalence and clinical outcome of right
      ventricular (RV) dysfunction among normotensive PE patients. METHODS: Inclusion
      criteria included: (1) Confirmed PE at Sir Run Run Shaw Hospital from January
      2001 to December 2004. (2) Normotensive. (3) Echocardiography done before
      therapy. RV dysfunction was assessed with echocardiography in the presence of one
      or more of the following criteria: RV dilatation, pulmonary hypertension as
      evidenced by pulmonary artery systolic pressure>30 mm Hg, pulmonary artery mean
      pressure>20 mm Hg and tricuspid regurgitant velocity>2.8 m/s. The clinical
      outcome of these two groups normotensive PE patients with and without RV
      dysfunction was analyzed. RESULTS: 57 cases of normotensive PE were included in
      this study. 27 of the 57 patients were judged to have RV dysfunction. There was
      no difference in age, gender, prevalence of deep venous thrombosis (DVT), cancer
      or other risk factors in these two groups. In the group with RV dysfunction, 5
      patients (19%) died as a result of PE. In comparison, in the group without RV
      dysfunction, only one patient died related to bladder cancer with multiple brain
      metastasis, so none of the patients of this group died directly related to PE.
      After therapy, 22 patients of this group became better and RV function also
      improved in short-term. CONCLUSIONS: The mortality related to PE in normotensive
      patients with RV dysfunction is significantly higher than those without. In
      patients with PE, echocardiography is quite useful because it can often help to
      detect RV dysfunction which is a significantly high risk of death. After therapy,
      RV function of normotensive patients with PE will improve in short-term.
      Echocardiography is an important means of evaluating of therapeutic outcome in
      pulmonary embolism.

PMID- 17445432
TI  - [The effect of different loading doses of clopidogrel on platelet aggregation].
AB  - OBJECTIVE: To compare the short-term efficacy and safety of high loading dose
      (600 mg) clopidogrel treatment with those of routine loading dose (300 mg) in
      patients with acute coronary syndrome and provide evidence for planning
      clopidogrel treatment. METHODS: 60 patients were randomized into two groups, One
      group received 300 mg loading dose clopidogrel, while the other received 600 mg
      and both were followed by 75 mg daily thereafter. Adenosine diphosphate (ADP) (5
      micromol/L and 20 micromol/L) induced platelet aggregation was examined at
      baseline (before administration), 2 hours and 6 hours after administration and
      the count of white blood cell and platelet 3 days after loading dose. The primary
      end points were hemorrhagic events, granulocytopenia and thrombocytopenia within
      3 days after administration. RESULTS: With a high-dose agonist (20 micromol/L
      ADP), loading doses of clopidogrel at 300 mg and 600 mg both produced greater
      inhibition of baseline ADP (20 micromol/L) induced aggregation 6 hours after
      administration than 2 hours [group of 300 mg: (29.75+/-12.11)% vs (43.63+/
      14.31)%, P<0.05. Group of 600 mg: (28.86+/-10.24)% vs (34.86+/-10.84)%, P<0.05].
      Treatment with clopidogrel at 600 mg loading dose had a marked earlier effect on
      platelet aggregation 2 hours after administration than that of 300 mg [(34.86+/
      10.84)% vs (43.63+/-14.31)%, P<0.05]. The platelet aggregation of the two groups
      tended towards similar at 6 hours after the procedure [(28.86+/-10.24)% vs
      (29.75+/-12.11)%, P>0.05]. There were no episodes of hemorrhagic events,
      granulocytopenia and thrombocytopenia within 3 days after the procedure.
      CONCLUSIONS: In Chinese patients with acute coronary syndrome platelet
      aggregation can be inhibited more rapidly and more effectively with clopidogrel
      at 600 mg loading dose when compared with that at 300 mg loading dose and the
      safety aspect between the two different loading doses is equivalent.

PMID- 17445435
TI  - [Vascular endothelial function and plasma free fatty acids in the high-risk
      population of type 2 diabetes].
AB  - OBJECTIVE: To study the vascular endothelial function and the level of plasma
      free fatty acids (FFA) in patients with type 2 diabetes mellitus (T2DM), their
      first degree relatives (FDRs) with normal glucose tolerance and subjects with
      impaired glucose tolerance (IGT) and to compare these with health control.
      METHODS: Endothelial-dependent vasodilation (EDV), plasma level of FFA, and
      insulin active index (IAI) were measured in 36 controls with normal glucose
      tolerance (16 men and 20 women), 57 FDRs (27 men and 30 women), 59 subjects with
      IGT (25 men and 34 women) and 35 patients with T2DM (15 men and 20 women).
      RESULTS: EDV was lower in FDRs, IGT and T2DM than that in the controls [FDRs
      (5.03+/-0.34)%, IGT (3.09+/-0.28)%, T2DM (2.62+/-0.29)%, controls (12.45+/
      3.37)%]. The plasma level of FFA was higher in FDRs, IGT and T2DM than that in
      the controls [FDRs (0.52+/-0.08) mmol/L, IGT (0.52+/-0.12) mmol/L, T2DM (0.59+/
      0.23) mmol/L, controls (0.46+/-0.18) mmol/L], IAI was lower in FDRs, IGT and T2DM
      than that in the controls (FDRs -4.20+/-0.38, IGT -4.41+/-0.72, T2DM -4.65+/
      0.64, controls -3.79+/-0.57), P<0.05. CONCLUSIONS: There are decreased IAI,
      impaired endothelial function and increased plasma level of FFA in the FDRs with
      normal glucose tolerance, subjects with IGT and patients with T2DM.

PMID- 17445437
TI  - [Bilateral sequential whole lung lavage in the same treatment session for
      pulmonary alveolar proteinosis].
AB  - OBJECTIVE: To study the safety and effectiveness of bilateral sequential whole
      lung lavage in the same treatment session for pulmonary alveolar proteinosis.
      METHODS: Twelve times bilateral sequential whole lung lavage in the same
      treatment session were performed under general anaesthesia using a double lumen
      endotracheal tube for 10 cases of pulmonary alveolar proteinosis. The volume of
      lavage, return volume and the return rate were calculated. The efficacy was
      evaluated according to the improvement of symptoms, pulmonary function and
      arterial blood gas analysis data. RESULTS: Twelve times bilateral sequential
      whole lung lavage in the same treatment session were performed successfully for
      the 10 cases of pulmonary alveolar proteinosis. The total volume of lavage was
      (26,417+/-7,064) ml, the return volume was (25,962+/-7,023) ml, the time of
      lavage was (192+/-26) minutes. The symptoms and chest radiograph were improved
      immediately after the procedure for all patients. The alveolar to arterial oxygen
      tension difference was decreased significantly. Arterial oxygen tensions were
      increased but no significant difference was reached. There was no significant
      immediate improvement for the pulmonary function. No complications were noted but
      pulmonary edema in one patient. CONCLUSION: Bilateral sequential whole lung
      lavage in the same treatment session is a safe and effective procedure for
      treatment of pulmonary alveolar proteinosis.

PMID- 17445438
TI  - [The 6-month outcome in patients with vertebrobasilar system cerebral
      infarction].
AB  - OBJECTIVE: To evaluate the 6-month outcome in patients with vertebrobasilar
      system cerebral infarction and discuss the correlation of different stroke
      localization and vascular lesions with poor outcome. METHODS: 168 patients with
      vertebrobasilar system cerebral infarction, who were admitted in 2003 were
      evaluated for neurologic impairment and functional handicap. The stroke
      localization and vascular lesions were evaluated systematically and multivariate
      logistic regression analysis of the 6-month outcome and correlative factors was
      performed. RESULTS: It was found that the incidence of poor 6-month outcome was
      19.6%. The mortality rate was 11.9% and major disability 7.7%. Patients with
      proximal, middle and distal territory involvement (RR=5.392, 95% CI 1.229-23.657,
      P<0.05), multiple vertebrobasilar intracranial territory involvement (RR=3.077,
      95% CI 0.993-9.537, P<0.05), acute occlusion of basilar artery (RR=11.766, 95% CI
      3.455-40.074, P<0.001), extracranial vertebral artery lesion (RR=4.376, 95% CI
      1.081-17.714, P<0.05) were more likely to have poor outcome. CONCLUSIONS: It is
      shown that vertebrobasilar occlusive disease may consist of a variety of
      different stroke localizations and vascular lesions, many with of the patients
      have good prognosis.

PMID- 17445439
TI  - [The significance of urinary podocytes in patients with active lupus nephritis].
AB  - OBJECTIVE: To assess the significance of urinary podocyte and its possible
      implication as a marker of activity of lupus nephritis. METHODS: The presence of
      podocytes in urinary sediment was detected with immunochemical staining using
      anti-podocalyxin antibody. The correlation of the number of urinary podocytes
      with activity index of renal pathological lesions, hematuria, and proteinuria was
      analyzed respectively. The proliferating podocytes in renal biopsy tissue and
      urine from patients with class IV lupus nephritis were examined with double
      immunohistochemical staining. RESULTS: Thirty-one patients with lupus nephritis
      undergoing renal biopsy were enrolled into the study. Renal pathological findings
      of the patients could be classified into WHO class III (25.8%), class IV (64.5%)
      and class V (9.7%). 90% of the patients had positive urinary podocytes. The
      number of urinary podocytes was strongly and positively correlated with the
      severity of hematuria (r=0.639, P=0.000) and glomerular pathological activity
      index (r=0.487, P=0.014) in patients of class III and class IV. The amount of
      proteinuria was not correlated with pathological activity index, even though all
      the patients had proteinuria. Furthermore, the number of urinary podocytes, the
      severity of hematuria and the amount of proteinuria were all decreased after
      treatment with methyl prednisone, cyclophosphamide or mycophenolate mofetil.
      Interestingly, the urinary podocytes could disappear even before the remission of
      hematuria and proteinuria after treatment. Proliferative podocytes were observed
      both in biopsied kidney tissue and urinary sediments in patients of class IV.
      CONCLUSION: The presence and the number of urinary podocytes can be used as a
      valuable marker to grade the activity of lupus nephritis and to evaluate the
      efficacy of steroid therapy.

PMID- 17445440
TI  - [Membrane and cytoplasmic expression of urokinase-type plasminogen activator
      receptor in synovial tissues of rheumatoid arthritis patients].
AB  - OBJECTIVE: To investigate the production of membrane-expressed urokinase-type
      plasminogen activator receptor (muPAR) and cytoplasmic-expressed uPAR (cuPAR) in
      synovial tissue from patients with rheumatoid arthritis (RA) and analyze their
      relationship with the severity of synovial inflammation in RA. METHODS: MuPAR and
      cuPAR were measured with indirect immunofluorescence (IIF) and immunoperoxidase
      histochemical analysis of the synovial tissue sections from 18 patients with RA,
      10 patients with osteoarthritis (OA) and 4 healthy subjects. The association of
      uPAR expression with the severity of synovitis in RA was then analyzed. RESULTS:
      MuPAR positive cells were detected in approximately (66.0+/-9.4)% of the RA
      synovial cells, distributed predominantly in vascular endothelial cells and
      fibroblast cells. While cuPAR positive cells were found in about (61.0+/-5.8)% of
      the RA synovial cells, including subsynovial and interstitial macrophage-like
      cells, mononuclear leukocytes and fibroblast cells. Both the muPAR and cuPAR
      expression were much more increased in RA synovial tissue than those in OA
      synovial tissue. Furthermore, the number of muPAR (r=0.672, P<0.01) and cuPAR
      (r=0.649, P<0.01) positive cells in synovial tissue was also found to be
      correlated significantly with the severity of synovial inflammation in RA
      patients. CONCLUSION: The up-regulated expression of muPAR in synovial vascular
      endothelial cells suggests an important role of this molecule in angiogenesis in
      RA and the increased production of cuPAR in synovial inflammatory cells indicates
      the involvement of cuPAR in the inflammatory process in RA.

PMID- 17445441
TI  - [A comparison of the therapeutic effects between related donor and unrelated
      donor allogeneic hematopoietic stem cell transplantation in treatment of
      leukemia].
AB  - OBJECTIVE: To compare the therapeutic effect for leukemia between related donor
      hematopoietic stem cell transplantation (RD-HSCT) and unrelated donor
      hematopoietic stem cell transplantation (URD-HSCT). METHODS: 115 patients
      received allo-HSCT, of whom 68 received RD-HSCT and 47 received URD-HSCT. All
      patients were HLA serologically matched. Total body irradiation plus
      cyclophosphamide was adopted in 56 cases and busulfan, Ara-C, cyclophosphamide
      conditioning regimen (modified BuCY) in 59 cases. T and B cell reconstitution at
      different time points was assayed with flow cytometer one year after
      transplantation. Graft versus host disease (GVHD) and early infection were
      observed after transplantation. The difference of haematopoietic and
      immunological reconstitution between the two groups were estimated with
      Independent-Samples T test. Kaplan-Meier survival analysis model was used to
      estimate the overall survival and the disease-free survival in the two groups.
      RESULTS: The time in WBC>1.0x10(9)/L was (13.1+/-2.4) d and (16.3+/-3.0) d
      (P=0.003), the time in PLT>20x10(9)/L was (14.9+/-6.6) d and (20.2+/-7.3) d
      (P=0.042), respectively, RD-BMT and URD-BMT. The time with WBC>1.0x10(9)/L was
      (12.5+/-2.9) d and (13.1+/-4.1) d (P=0.488), the time with PLT>20x10(9)/L was
      (12.2+/-4.2) d and (15.7+/-7.1) d (P=0.020), respectively, in RD-PBSCT and URD
      PBSCT. The reconstitution of CD4+CD3+ at 1st, 3rd, 6th, 9th, 12th month,
      CD45RA+CD4+ at 1st month and CD8+CD3+ at 3rd month was different significantly
      between RD-HSCT and URD-HSCT. The incidence of II-IV acute GVHD, chronic GVHD and
      lethality of GVHD was 45.5% and 52.3%, 45.3% and 63.2%, 6.1% and 15.9%,
      respectively, in RD-HSCT and URD-HSCT groups. The relapse rate was 18.2% and
      11.4%, respectively, in RD-HSCT and URD-HSCT groups. The incidence of early
      infection was 42.4% and 47.7% (P=0.696), respectively, in RD-HSCT and URD-HSCT
      groups. The overall survival and the disease-free survival rates at three-year
      follow-up were (67.8+/-6.9)% and (61.6+/-7.7)% (P=0.133), (62.3+/-6.9)% and
      (56.8+/-7.9)% (P=0.177), respectively, in RD-HSCT and URD-HSCT groups.
      CONCLUSION: The therapeutic effect for leukemia is proximate in RD-HSCT and URD
      HSCT.

PMID- 17445443
TI  - [Low dose heparin for the prevention of hepatic veno-occlusive disease after
      allogeneic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To explore the safety and efficacy of low dose heparin for the
      prevention of hepatic veno-occlusive disease (VOD) after allogeneic hematopoietic
      stem cell transplantation (allo-HSCT) conditioned with busulfan and
      cyclophosphamide (BU-CY2) and the ideal time frame of the heparin administration.
      METHODS: From April 1997 to December 2005, 134 patients (75 male, 59 female;
      median age 25 years old) were transplanted in our bone marrow transplantation
      unit. All patients were conditioned with BU-CY2 or busulfan-based regimen and
      scheduled to receive a continuous injection of heparin at a dose of 100 IUxkg-1xd
      1. The patients were divided into different groups: 87 patients received related
      donor transplantation and 47 patients unrelated donor transplantation; 40
      patients had abnormal liver function prior to transplantation and the remaining
      94 patients normal liver function; 68 patients received heparin from day -7 to
      day +21 post HSCT and the other 66 patients from day -7 to day +14. RESULTS: All
      134 patients had sustained engraftment. The median time for neutrophils to reach
      0.5 x 10(9)/L and for platelets to reach 20x10(9)/L were 12 days (range 9-28) and
      20 days (range 6-65), respectively. The disease-free survival at day +100 for
      leukemia patients was 82.2% (97/118). None of 134 patients developed VOD (0%),
      including 10 patients with class 3 thalassemia major. The incidence and severity
      of clinical bleeding events in 15 patients monitored with prothrombin time and
      activated partial thromboplastin time is comparable with those not monitored.
      CONCLUSIONS: It is suggested that low dose heparin alone is effective and safe
      for the prophylaxis of VOD following allo-HSCT conditioned with BU-CY regimen.
      Shortening the duration of administering heparin from -7 d to +21 d to -7 d to
      +14 d does not affect the effectiveness of low dose heparin to prevent VOD.

PMID- 17445463
TI  - [Multidisciplinary combination therapy for lung cancer].

PMID- 17445464
TI  - [Challenge and up-to-date of molecule target therapy in lung cancer].

PMID- 17445465
TI  - [Role of adjuvant chemotherapy in resected non-small cell lung cancer-controversy
      and consensus].

PMID- 17445466
TI  - [To improve the survival rate of patients suffering from locally advanced non
      small cell lung cancer with combination of radiotherapy and chemotherapy].

PMID- 17445467
TI  - [Advances in non-small cell lung cancer chemotherapy].

PMID- 17445468
TI  - [Standardized therapy and progression for patients with small cell lung cancer].

PMID- 17445469
TI  - [Gefitinib target treatment in non-small cell lung cancer].
AB  - OBJECTIVE: To evaluate the efficacy, target population and influencing factors of
      Gefitinib in patients with non-small-cell lung cancer (NSCLC) pretreated with
      platinum. METHODS: Patients with NSCLC who had been previously treated with at
      least one course of platinum based chemotherapy received 250 mg oral doses of
      Gefitinib once daily till disease progression. Response rate, progression free
      survival, overall survival and toxicity profile were analyzed. Kaplan-Meier
      method was used to analyze the survival rate. Cox regression was used to define
      the predictive factors. RESULTS: A hundred and fifteen patients were enrolled
      into the study from July 2001 to May 2005. The follow-up was ended on Sep. 30,
      2006. Median follow up time was 30 months. The compliance rate was 100%. The
      median symptom improving time was 8 days. Complete response rate was 4.3%
      (5/115), partial response 39.1% (45/115), stable disease 27.0% (31/115) and
      progressive disease 29.6% (34/115). Response rate was 43.5% (50/115). Disease
      control rate was 70.4% (81/115). The median progression-free survival and median
      overall survival were 8 and 11 months, respectively. One and two-year progression
      free survival rates and overall survival rates were 32.2% (events 78), 5.6%
      (events 103) and 41.7% (death 67), 21.5% (death 87) respectively; 3-year overall
      survival 12.3% (death 93). Adenocarcinoma was the only predictor for therapeutic
      effect in the Cox model (P = 0.004). The primary failure to gefitinib was due to
      brain metastasis (39.4%, 28/71). Grade III skin toxicity was found in 5.2%
      (6/115) patients. CONCLUSION: Gefitinib is the drug of choice for patients with
      heavily pretreated stage III(B) and IV adenocarcinoma of NSCLC with safe and
      accepted toxicity profile.

PMID- 17445470
TI  - [Distinguishing second primary tumors from lung metastasis in patients with
      postoperative non-small cell lung cancer by microsatellite analysis].
AB  - OBJECTIVE: In patients with resected early stage non-small cell lung cancer
      (NSCLC), intrapulmonary solitary tumor represents either second primary tumor
      (SPT) or a metastasis. This study is to discern SPT from lung metastasis in
      patients with postoperative NSCLC followed a solitary intrapulmonary tumor by
      microsatellite analysis. METHODS: Twenty-one patients with stage I - III(A) NSCLC
      resected by surgery during 1994.1 - 2002.8 were studied. Paired tumors from 21
      patients with NSCLC and a solitary lung nodule were analyzed for their loss of
      heterozygosity (LOH) on chromosomal arms 3p, 9p and 17p. DNA from microdissected
      tumors and non-malignant lung tissues was subjected to polymerase chain reaction
      based microsatellite analysis using 8 microsatellite markers. An effort was also
      made to distinguish SPT from lung metastasis on the basis of clinical and
      histopathologic features. RESULTS: The paired tumors from 7 patients had
      concordant patterns of LOH at all microsatellite loci suggesting the same clonal
      origin, and supporting metastatic spread, where 4 paired tumors had discordant
      patterns of at all loci suggesting independent tumor origin. These observations
      were supported by the clinical and pathologic findings. Additional 6 paired
      tumors had concordant allelic loss on 3p and discordant loss on the other,
      clinical characteristics supporting metastatic disease. In contrast, 2 paired
      tumors had concordant allelic loss on 9p or 17p but discordant loss on the 3p,
      clinical data supporting SPT. CONCLUSIONS: The paired tumors from 7 patients had
      concordant patterns of LOH at all microsatellite loci suggesting the same clonal
      origin, and supporting metastatic spread, where 4 paired tumors had discordant
      patterns of at all loci suggesting independent tumor origin. These observations
      were supported by the clinical and pathologic findings. Additional 6 paired
      tumors had concordant allelic loss on 3p and discordant loss on the other,
      clinical characteristics supporting metastatic disease. In contrast, 2 paired
      tumors had concordant allelic loss on 9p or 17p but discordant loss on the 3p,
      clinical data supporting SPT.

PMID- 17445471
TI  - [Prolonged hypoxia induces GST-pi expression and drug resistance in lung
      adenocarcinoma cell line SPCA1].
AB  - OBJECTIVE: To investigate the association of hypoxia with GST-pi expression in
      lung adenocarcinoma cells SPCA1 and the drug resistance in hypoxic condition.
      METHODS: RNA and protein in SPCA1 cells treated with hypoxia (0.5% O(2)) for 16 h
      were isolated. HIF-1alpha and GST-pi mRNA expression was detected by real time RT
      PCR, and HIF-1alpha protein was detected by Western blotting analysis. GST-pi
      protein was finally analyzed on a FACScan flow cytometer using Cellquest
      software. Sensitivity of Doxorubicin and Mitomycin in hypoxic SPCA1 cells was
      detected using cell clonogenic assay. RESULTS: HIF-1alpha expression was up
      regulated on mRNA and protein levels in hypoxic SPCA1 cells, so as was GST-pi
      expression. Doxorubicin resistance was increased, but hypoxia had no significant
      influence on Mitomycin resistance. GST-pi expression had no significant change
      after HIF-1alpha was down-regulated by RNA interfering. CONCLUSION: Though
      prolonged hypoxia can induce GST-pi expression and increase drug resistance such
      as to Doxorubicin, HIF-1alpha expression has no correlation with GST-pi
      expression.

PMID- 17445472
TI  - [Expression of T-bet, GATA-3 and FOXP3 mRNA in asthmatic peripheral blood
      mononuclear cells stimulated by Dermatophagoides farinae antigen].
AB  - OBJECTIVE: To study the expression of T-bet, GATA-3 and FOXP3 mRNA in asthmatic
      peripheral blood mononuclear cells (PBMC) before and after stimulation by
      Dermatophagoides farinae antigen (Df), and the relationship among the three
      transcription factors. METHODS: Twenty-five patients of asthma and 15 healthy
      controls were included. The mRNA levels of T-bet, GATA-3, and FOXP3 in PBMC
      before and after Df stimulation were detected by semiquantitative reverse
      transcription-polymerase chair reaction (RT-PCR). RESULTS: There was no
      statistical difference (t = 0.78, 0.38 respectively, all P > 0.05) in the levels
      of T-bet and FOXP3 mRNA between the patients (0.3 +/- 0.4, 0.42 +/- 0.24
      respectively) and the healthy controls (0.4 +/- 0.3, 0.39 +/- 0.37 respectively).
      However, GATA-3 mRNA was statistically different (t = 2.27, P < 0.05) between the
      patients (1.0 +/- 0.3) and the healthy controls (0.8 +/- 0.3). After the
      stimulation of PBMC by Df, the levels of T-bet, GATA-3 and FOXP3 mRNA showed
      statistical difference (t = 2.30, 3.79, 2.08 respectively, P < 0.05, < 0.01, <
      0.05 respectively) between the patients (0.33 +/- 0.39, 1.58 +/- 1.44, 0.11 +/-
      0.32 respectively) and the healthy controls (0.03 +/- 0.40, 0.11 +/- 0.53, 0.43
      +/- 0.66 respectively). The FOXP3 mRNA level in the asthmatics was negatively
      correlated with T-bet and GATA-3 mRNA (r = -0.46, P < 0.05, r = -0.62, P < 0.01
      respectively). CONCLUSIONS: There are a predominant expression of GATA-3 and T
      bet, but a decreased expression of FOXP3 in Df-stimulated PBMCs from patients
      with asthma.

PMID- 17445473
TI  - [Effect of rosiglitazone on the expression of T-bet/GATA-3 in T lymphocytes in
      patients with acute asthma].
AB  - OBJECTIVE: To investigate the effect of rosiglitazone on the expression of T
      bet/GATA-3 in peripheral blood T lymphocytes and cytokine derived from Th1/Th2 in
      patients with acute asthma and to compare its mechanism with that of
      dexamethasone (DXM). METHODS: Peripheral blood T lymphocytes from 10 patients
      with acute asthma (A group, A) and 10 healthy volunteers (B group, B) were
      isolated, purificated and cultured, and were divided into 2 groups (3 h and 24 h)
      based on the treatment time, and each group was further divided, on the basis of
      the treatment given, into 3 sub-groups respectively: control group (A(1) and
      B(1)), rosiglitazone treated group (A(2) and B(2)) and DXM treated group (A(3)
      and B(3)). The levels of IFN-gamma and IL-4 in the culture supernatant were
      detected by Enzyme-linked immunoadsorbent assay (ELISA) and the expression levels
      of T-bet mRNA/GATA-3 mRNA in T lymphocytes was detected by Reverse Transcription
      Polymerase Chain Reaction (RT-PCR). RESULTS: The levels of INF-gamma and INF
      gamma/IL-4 in the culture supernatant of T lymphocytes and T-bet mRNA and T-bet
      mRNA/GATA-3 mRNA in T lymphocytes from the A at 3 h and 24 h were 357 +/- 31, 783
      +/- 47, 5.5 +/- 1.0, 8.4 +/- 1.5, 18.7 +/- 3.7, 11.9 +/- 2.9, 1.20 +/- 0.11,
      0.290 +/- 0.020, and those from the B at 3 h and 24 h were 659 +/- 41, 1394 +/-
      120, 11.5 +/- 3.0, 17.4 +/- 4.0, 29.0 +/- 4.0, 18.9 +/- 4.0, 3.82 +/- 0.81, 0.870
      +/- 0.090, the differences were significant between these groups (t = 18.59,
      5.95, 14.87, 6.25, 6.06, 4.63, 10.23, 18.67, all P < 0.05, respectively). The
      levels of IL-4 in the culture supernatant of T lymphocytes and GATA-3 mRNA in T
      lymphocytes from the A at 3 h and 24 h were 65 +/- 6, 96 +/- 9, 16.4 +/- 4.2, 41
      +/- 6, and those from the B at 3 h and 24 h were 57 +/- 5, 83 +/- 7, 7.8 +/- 2.2,
      23 +/- 4, the differences were significant between these groups (t = 3.19, 3.90,
      5.77, 7.76, all P < 0.05, respectively). The levels of IFN-gamma, IL-4 and IFN
      gamma/IL-4 in the culture supernatant of T lymphocytes from the A and B at 3 h
      were 357 +/- 31, 65 +/- 6, 5.5 +/- 1.0, 659 +/- 41, 57 +/- 5, 11.5 +/- 3.0, and
      those from the A and B at 24 h were 783 +/- 47, 96 +/- 9, 8.4 +/- 1.5, 1394 +/-
      120, 83 +/- 7, 17.4 +/- 4.0, The differences were significant between these
      groups (t = 23.8, 9.48, 5.03, 18.21, 9.01, 3.53, all P < 0.05, respectively). The
      levels of T-bet mRNA and T-bet mRNA/GATA-3 mRNA in T lymphocytes from the A and B
      at 3 h were 18.7 +/- 3.7, 1.20 +/- 0.11, 29.0 +/- 4.0, 3.82 +/- 0.81, and those
      from the A and B at 24 h were 11.9 +/- 2.9, 0.290 +/- 0.020, 18.9 +/- 4.0, 0.870
      +/- 0.090, the differences were significant between these groups (t = 4.62, 5.66,
      29.67, 11.5, all P < 0.05, respectively). The levels of GATA-3 mRNA in T
      lymphocytes from the A and B at 3 h were 16.4 +/- 4.2, 7.8 +/- 2.2, it was lower
      than those from the A and B at 24 h (41 +/- 6, 23 +/- 4, t = 10.70, 10.11, all P
      < 0.05, respectively). The levels of T-bet mRNA from the A showed a positive
      correlation with the level of IFN-gamma (r = 0.581, P < 0.05), and a negative
      correlation with the level of IL-4 (r = -0.493, P < 0.05); The levels of GATA-3
      mRNA from the A showed a negative correlation with the level of IFN-gamma (r = 
      0.501, P < 0.05), and a positive correlation with the level of IL-4 (r = 0.579, P
      < 0.05); The ratio of T-bet mRNA to GATA-3 mRNA from the A showed a positive
      correlation with the ratio of IFN-gamma to IL-4 (r = 0.696, P < 0.05).
      CONCLUSION: Rosiglitazone could regulate the balance of IFN-gamma and IL-4
      through effect on the expression of T-bet mRNA and GATA-3 mRNA.

PMID- 17445474
TI  - [Analysis of misdiagnosis of tuberculosis in the synovial sheath].
AB  - OBJECTIVE: To investigate the factors for misdiagnosis of tuberculosis in
      synovial sheath, and therefore to improve the early diagnosis of the disease.
      METHODS: From January 1991 to December 2003, 15 cases of tuberculosis in the
      synovial sheath were treated using surgery and anti-tuberculous agents. The
      clinical features and the related factors for misdiagnosis were analyzed.
      RESULTS: The duration from onset of symptom and sign to a final diagnosis was (16
      +/- 10) months (range from 2 to 36 months). Twelve cases were misdiagnosed before
      surgery. All cases were followed up for 2.5 to 7 years without recurrence, except
      one case of systemic lupus erythematosus complicated with tuberculosis of the
      wrist and the ankle 1 month after operation. CONCLUSION: Lack of specific
      symptoms and signs, nonspecific radiological manifestations and over-dependence
      on laboratory examinations were the major factors responsible for early
      misdiagnosis.

PMID- 17445475
TI  - [Tuberculosis after organ transplantation: clinical analysis and literature
      review].
AB  - OBJECTIVE: To describe the clinical features, diagnosis and treatment of
      tuberculosis after organ transplantation. METHOD: The clinical data of 25 cases
      of tuberculosis after organ transplantation were retrospectively analyzed.
      RESULTS: Sixty-eight percent of the patients presented only mild symptoms. Fever,
      cough, malaise and chest tightness were among the most common manifestations.
      Pulmonary tuberculosis, pleurisy, miliary lesions, lymph node disease, and kidney
      tuberculosis were common. Involvement of two organs were present in 72% (18/25)
      of the patients. Radiology showed soft lesions, miliary nodules, pleural
      effusion, hilar and mediastinal lymphadenopathy. Bacteriology and histology were
      used to confirm the diagnosis in most cases. The average time from presentation
      to diagnosis was 38 d. The effective rate of therapy was 76% (19/25). CONCLUSION:
      More attention should be paid to tuberculosis after organ transplantation and
      immunosuppression. Prompt diagnosis and treatment are important measures to
      reduce the mortality.

PMID- 17445476
TI  - [The effect of inhaled nitric oxide on endothelium-derived angiokinetic factors
      in patients with acute high altitude disease].
AB  - OBJECTIVE: To study the effect of inhaled nitrogen monoxidum (NO) on endothelium
      derived angiokinetic factors including NO, endothelin (ET), thromboxane B(2)
      (TXB(2)) and 6-keto-prostaglandin F(1a) (6-Keto-PGF(1a)) in patients with acute
      high altitude disease. METHODS: Forty-seven patients with acute high altitude
      disease were selected and divided into two groups randomly: twenty-three cases as
      a routine medical treatment group, for which oxygen, aminophylline, dexamethasone
      and furosemide were used, while 24 cases as a NO treatment group, for which only
      inhalation of 0.001% NO gas with air balanced in plateau (altitude 3658 m), were
      given twice daily (AM and PM each for an hour). The level of serum NO, ET, TXB(2)
      and 6-Keto-PGF(1a) were measured, and the changes of clinical symptoms were
      scored using the Lake Louise acute high altitude disease scoring. RESULTS: In the
      two groups, the level of ET [(78 +/- 8) and (69 +/- 5) ng/L], TXB(2) [(87 +/- 13)
      and (73 +/- 8) ng/L], ET/NO [(26.7 +/- 1.5) x 10(3) and (21.8 +/- 1.1) x 10(3)],
      TXB(2)/6-Keto-PGF(1a) (0.84 +/- 0.36 and 0.58 +/- 0.11, clinical symptom score
      2.4 +/- 1.6 and 1.8 +/- 1.3) after treatment were decreased significantly as
      compared to the levels of ET [(83 +/- 8) and (84 +/- 4) ng/L], TXB(2) [(102 +/-
      16) and (103 +/- 13) ng/L], ET/NO [(35.0 +/- 2.7) x 10(3) and (36.3 +/- 3.1) x
      10(3)], TXB(2)/6-Keto-PGF(1a) (1.28 +/- 0.38 and 1.24 +/- 0.28), clinical symptom
      score (4.4 +/- 2.3 and 4.4 +/- 2.0) before treatment. After treatment, the level
      of NO [(2880 +/- 537) and (3167 +/- 192) microg/L] and 6-Keto-PGF(1a) [(122 +/-
      46) and (128 +/- 15) ng/L] were significantly higher than the level of NO [(2372
      +/- 144) and (2313 +/- 188) microg/L] and 6-Keto-PGF(1a) [(86 +/- 28) and (86 +/-
      13) ng/L] before treatment. CONCLUSION: Inhaled NO is an effective treatment for
      high altitude disease in plateau, probably by modulating the angiokinetic
      factors.

PMID- 17445477
TI  - [The role of CD8+CD28- regulatory T lymphocytes in pulmonary tuberculosis].
AB  - OBJECTIVE: To study the role of CD(8)(+)CD(28)(-) regulatory T cells in
      tuberculosis. METHODS: The positive rates of CD(3)(+)CD(8)(+)CD(28)(-) T cells,
      CD(3)(+) T cells, CD(3)(+)CD(8)(+) T cells and CD(8)(+)CD(28)(+) T cells, and the
      content of IL-6 in CD(8)(+)CD(28)(-) T cells in leukocytes of peripheral blood
      from 15 patients with pulmonary tuberculosis, 15 patients with chronic bronchitis
      and 15 healthy controls were detected by flow cytometry. RESULTS: The positive
      expression rates of CD(3)(+) T cells of tuberculosis group [(41 +/- 16)%] and
      bronchitis controls [(40 +/- 10)%] were significantly lower than those from
      healthy controls [(44 +/- 6)%] respectively, but no differences were found
      between tuberculosis group and bronchitis controls. The CD(3)(+)CD(8)(+) T cells
      in CD(3)(+) T cells from the tuberculosis group [(47 +/- 16)%] and bronchitis
      controls [(44 +/- 10)%] were significantly higher than those from the healthy
      controls [(41 +/- 12)%] respectively, but no differences were found between the
      tuberculosis group and bronchitis controls. The CD(8)(+)CD(28)(+) T cells in
      CD(3)(+) T cells from tuberculosis group [(15 +/- 8)%] and bronchitis controls
      (20 +/- 7%) were significantly lower than those from healthy controls [(32 +/-
      9)%] respectively, and those of the tuberculosis group were significantly lower
      than those from the bronchitis controls. CD(8)(+)CD(28)(-) T cells in CD(3)(+) T
      cells from tuberculosis group [(27 +/- 9)%] and bronchitis controls [(22 +/- 9)%]
      were significantly higher than those from healthy controls [(10 +/- 4)%]
      respectively, and those of the tuberculosis group were significantly higher than
      those of the bronchitis controls. The level of IL-6 secreted by CD(8)(+)CD(28)(-)
      T cells from tuberculosis group [(32.4 +/- 2.4)%] was significantly higher than
      bronchitis controls [(19.7 +/- 3.2)%] and healthy controls [(15.2 +/- 2.7)%] and
      no differences were found between bronchitis controls and healthy controls.
      CONCLUSIONS: The number of CD(8)(+)CD(28)(-) T cells and their production of IL-6
      in the peripheral blood of tuberculosis patients are significantly increased as
      compared with the control groups, while the number of CD(8)(+)CD(28)(+) T cells
      (cytotoxic T cell) is significantly decreased. The results suggest that these
      cells and IL-6 may be involved in the pathogenesis of pulmonary tuberculosis.

PMID- 17445478
TI  - [Therapeutic effects of granulysin/interleukin-12 recombinant M. smegmatis in a
      murine model of M. tuberculosis infection].
AB  - OBJECTIVE: To study the effects and mechanisms of recombinant Mycobacterium
      smegmatis (M. smegmatis) encoding human granulysin and murine interleukin-12 (IL
      12) on murine M. tuberculosis infection. METHODS: Balb/c mice infected with M.
      tuberculosis were treated with normal saline, M. smegmatis, pZM03, recombinant M.
      smegmatis respectively. The numbers of viable bacteria in the lung and the spleen
      were counted. The levels of IL-12, IgG(2a) in serum and interferon-gamma (IFN
      gamma) released from spleen lymphocytes stimulated with purified protein
      derivative (PPD) were detected with enzyme linked immunosorbent assay (ELISA).
      The expression of granulysin in tissue was detected with immunohistochemistry.
      Lungs and spleens were prepared for pathological analysis. RESULTS: The
      recombinant M. smegmatis group [(4.57 +/- 0.28) in lung, (3.47 +/- 0.25) in
      spleen] showed significantly reduced number of colony forming units (log CFU/g)
      compared with the control [(5.77 +/- 0.12) in lung, (4.66 +/- 0.18) in spleen],
      M. smegmatis [(5.62 +/- 0.14) in lung, (4.65 +/- 0.26) in spleen] and pZM03
      [(5.04 +/- 0.22) in lung, (4.25 +/- 0.48) in spleen] group. The expression of
      granulysin in tissue, and increased level of IL-12 and IgG(2a) in serum were
      found in recombinant M. smegmatis group. IFN-gamma released from spleen
      lymphocytes stimulated with PPD in recombinant M. smegmatis group and pZM03 group
      was higher than that of other groups, but the difference between recombinant M.
      smegmatis group and pZM03 group was not significant. The pathological changes in
      lungs of the recombinant M. smegmatis group were localized, while those in the
      control group were extensive. Significant pathological changes were not found in
      the spleens of all groups. CONCLUSION: The recombinant M. smegmatis had
      immunotherapeutic effects, which were associated with a switch to Th1 response
      and the antibacterial activity of granulysin.

PMID- 17445479
TI  - [Mechanisms of resistance to epidermal growth factor receptor tyrosine kinase
      inhibitors in non-small cell lung cancer].

PMID- 17445493
TI  - Neurosarcoidosis.
AB  - Neurosarcoidosis is an uncommon disorder and requires a careful clinical
      evaluation to reach a diagnosis. Generally, patients with peripheral symptoms,
      which include paresthesias, muscle weakness, and stocking glove deficits, have a
      better outcome compared with those with central nervous system involvement.
      Patients with mass lesions or hydrocephalus tend to have more relapses and are
      often more resistant to routine therapy. Neurosarcoidosis often responds to
      glucocorticoids, usually within days or weeks of initiating therapy. Patients are
      usually maintained on 40 to 80 mg per day for 4 to 6 weeks, which is then tapered
      slowly. Alternative treatments for refractory neurosarcoidosis, or to reduce or
      eliminate steroids, include methotrexate, cyclophosphamide, azathioprine,
      cyclosporine, infliximab, chlorambucil, chloroquine, and hydroxychloroquine.

PMID- 17445494
TI  - Primary angiitis of the central nervous system.
AB  - Primary angiitis of the central nervous system (PACNS) is a rare disorder that
      must be differentiated from secondary CNS vasculitides, reversible cerebral
      vasoconstriction syndromes, and other vascular disorders. Because of the rarity
      of PACNS, no controlled trials have been performed, thereby precluding an
      evidence-based approach to therapy. PACNS has been considered to have three major
      subsets, as defined by clinical, laboratory, angiographic, and pathologic
      findings: granulomatous angiitis of the central nervous system (GACNS), benign
      angiopathy of the central nervous system (BACNS), and atypical PACNS.
      Approximately 5% of cases may present as a tumor-like mass lesion. Because the
      subset of patients with GACNS has a more guarded prognosis, treatment with high
      dose glucocorticoids and cyclophosphamide is necessary. All patients with
      atypical PACNS should be treated with high-dose glucocorticoids initially. The
      use of additional immunosuppressive agents depends on the severity of the initial
      presentation, the ability to achieve remission with glucocorticoid monotherapy,
      and the occurrence of relapse upon glucocorticoid tapering. PACNS mass lesions
      can regress completely with immunosuppressive therapy, and therefore, surgical
      excision may be avoided. Patients with BACNS should be treated with a calcium
      channel blocker (eg, verapamil) with or without a short course of
      glucocorticoids. These patients should not receive additional immunosuppressive
      therapies such as cyclophosphamide. This reflects the fact that BACNS is now more
      correctly considered as a reversible cerebral vasoconstriction syndrome (RCVS)
      and not as a true vasculitis. However, a patient initially diagnosed with RCVS
      that demonstrates incomplete resolution of angiographic findings after 3 to 4
      months should be re-evaluated for alternative diagnoses, including PACNS.

PMID- 17445495
TI  - Current treatment options in multiple sclerosis.
AB  - Advances in our understanding of the pathogenesis of multiple sclerosis (MS)
      lesions are leading to the development of more targeted therapies. Axonal
      transection is likely an important cause of accumulating disability in disease
      progression and suggests the importance of early and aggressive therapy. Early
      treatment with disease-modifying therapy should be considered in patients with
      first episode of demyelination and presence of MRI lesions consistent with MS.
      Intravenous steroids are the mainstay of treatment of acute MS exacerbations.
      Although their benefits must be weighed against the potential for complications,
      natalizumab and mitoxantrone significantly decrease relapses and MRI lesions in
      patients with relapsing MS. Many new therapies, including oral and infrequently
      administered infusion therapies, are currently in phase III trials and will
      likely become available over the next 3 to 4 years.

PMID- 17445496
TI  - Management of impulse control disorders in Parkinson's disease.
AB  - Impulse control disorders (ICDs) are a set of behaviors, including pathologic
      gambling, hypersexuality, compulsive shopping, compulsive eating, and punding,
      which are now recognized to occur in a subset of patients with Parkinson's
      disease (PD). Although the underlying pathophysiology of these behaviors is
      poorly understood, they appear to be associated with the use, and sometimes
      overuse, of dopaminergic agents prescribed for the treatment of the motor
      symptoms of PD. At present, there are limited data to support any particular
      therapeutic strategy. Approaches worth considering in the management of the PD
      patient with an ICD include reduction or discontinuation of dopamine agonist
      therapy, trials of various pharmacologic agents, psychosocial interventions, and
      deep brain stimulation of the subthalamic nucleus. However, the management of
      each patient must be tailored for the particular clinical setting, and the
      development of evidence-based treatment strategies awaits future prospective
      studies and randomized controlled trials.

PMID- 17445498
TI  - Treatment of Levodopa-induced Dyskinesia.
AB  - Levodopa provides the most effective symptomatic treatment for Parkinson's
      disease (PD). Initiation of treatment of PD too early and/or very aggressive
      treatment with large doses of levodopa results in severe motor fluctuations and
      dyskinesias in 30% of patients with PD. Chronic levodopa treatment over a period
      of 9 years or more will invariably result in disabling motor fluctuations in 90%
      of PD patients. The motor fluctuations and associated dyskinesia are due to
      progressive dopamine denervation, an unregulated pattern of release of dopamine
      in the synapse, fluctuating levels of receptor sensitivity, and fluctuating
      levels of dopamine receptor stimulation. Once the dyskinesias are established,
      they are difficult to treat. The current medical therapy is a by-product of
      several explorative open-label trials, as well as a few blinded and double-label
      placebo-controlled clinical trials, of varying duration in a small number of
      patients. These studies suggest that amantadine, a glutamate antagonist, may be
      the most effective, easily available, and inexpensive medical treatment for
      levodopa-induced dyskinesia. Several other drugs, already approved for other
      medical ailments, also have been tried but not evaluated in large-scale clinical
      trials. None of these drugs is approved by the US Food and Drug Administration
      specifically for levodopa-induced dyskinesia. By far, the most effective
      treatment of levodopa-induced dyskinesia appears to be deep brain stimulation,
      with globus pallidus interna or the subthalamic nucleus as the two major targets
      of placement of electrodes.

PMID- 17445497
TI  - Nutritional therapies in Parkinson's disease.
AB  - Advise patients with Parkinson's disease (PD) to consume a balanced diet, with
      special attention to adequate intake of dietary fiber, fluids, and macro- and
      micronutrients. Regularly reassess patients' nutritional history and
      anthropomorphic measures (height and weight), particularly in patients with
      advanced disease. PD-related psychosocial as well as physical and cognitive
      limitations increase susceptibility to subacute and chronic malnutrition.
      Nutritional requirements may change with PD progression or after surgical therapy
      for PD. Patients and caregivers may benefit from counseling by a dietician who is
      knowledgeable about the nutritional risks and needs of PD. Regularly inquire
      about dysphagia symptoms, and consider speech therapy consultation for clinical
      and modified barium-swallowing evaluations and management recommendations.
      Although non-oral delivery options of dopaminergic therapy are increasing, severe
      dysphagia may warrant percutaneous endoscopic gastrostomy tube placement for
      nutritional support and more reliable PD medication dosing. Analyze vitamin B(12)
      and D concentrations at regular intervals. Both vitamins are frequently deficient
      in elderly persons but may not be routinely checked by primary care physicians.
      Record over-the-counter and nutritional supplement medications at each visit, and
      assist patients in periodically re-evaluating their potential benefits, side
      effects, drug interactions, and costs. To date, clinical trials of antioxidant
      vitamins and nutritional supplements have provided insufficient evidence to
      support routine use for PD in the clinic. Data from several clinical trials of
      antioxidant vitamins/nutritional supplements are expected in the near future.
      Consider altering medication dosing in relation to meals to help with mild to
      moderate motor fluctuations. Patients with severe motor fluctuations may benefit
      from adapting the 5:1 carbohydrate-to-protein ratio in their daily meals and
      snacks. Following a "protein redistribution" diet is logistically more difficult
      and less palatable, and therefore less frequently recommended. To ensure adequate
      protein intake, a registered dietician should supervise patients who follow
      either of these diets.

PMID- 17445499
TI  - Current and future treatments in multiple system atrophy.
AB  - Multiple system atrophy (MSA) is an atypical parkinsonian disorder characterized
      clinically by the development of parkinsonism, autonomic dysfunction,
      corticospinal degeneration, and cerebellar abnormalities. The cause of MSA is
      unknown, and progression is usually faster than idiopathic Parkinson's disease.
      No treatment is currently available to prevent or slow the progression of this
      neurodegenerative disorder. Available treatments are primarily symptomatic. This
      article reviews the current treatment options available for MSA in addition to
      emerging therapies in neuroprotection and neurotransplantation. Research into the
      neuropathology of MSA is being conducted and could lead to new more effective
      treatments within the next decade. The management for this disorder currently
      includes symptomatic and palliative strategies, as well as family education and
      support; the ultimate goal is to improve the quality of life for patients and
      their caregivers.

PMID- 17445500
TI  - Botulinum toxin in the management of dystonia.
AB  - Dystonia is a neurologic disorder that can occur at any age and often results in
      significant disability. The therapeutic application of botulinum toxin has
      revolutionized the treatment of this disorder, particularly for the adult-onset
      focal forms such as cervical dystonia and blepharospasm. The two available
      commercial preparations, botulinum toxin types A and B, have been shown to be
      equally efficacious in cervical dystonia and are both reasonable first-line
      choices for treating other forms of focal dystonia. Preliminary studies have
      suggested that differences in tolerability and immunogenicity may exist between
      the two preparations, but this has not been adequately evaluated. Because of high
      cost, complicated administration, potentially serious side effects, and the risk
      of developing immunoresistance, this treatment should be administered only by a
      physician with sufficient background in the diagnosis and treatment of dystonia,
      to ensure optimal outcomes.

PMID- 17445501
TI  - Stiff-person syndrome.
AB  - Classic stiff-person syndrome (SPS) is a clinically diagnosed disease
      characterized by axial and often appendicular rigidity with lumbar hyperlordosis
      and painful spasms. Supportive data include increased glutamic acid decarboxylase
      autoantibody titers more than 20 nmol/L, a needle electromyography with
      continuous motor unit activity in at least one axial muscle, and normal MRI and
      cerebrospinal fluid studies. Variants of SPS include those with focal limb
      dysfunction (stiff-limb syndrome), encephalomyelitis ("SPS plus"), and those
      associated with paraneoplastic autoantibodies. Although the precise mechanism is
      unknown, an autoimmune etiology for SPS is proposed, based on its association
      with autoantibodies and other autoimmune diseases and its response to
      immunomodulatory therapy. The cornerstone of treatment consists of symptomatic
      care with benzodiazepines and/or baclofen. Other neuromodulators include
      antiepileptic medications and muscle relaxants. Continued disability despite
      first-line therapy should prompt consideration of agents aimed at
      immunomodulation and immunosuppression. Intravenous immunoglobulin is one of the
      few agents to be evaluated in a double-blind, randomized controlled trial. Other
      options include steroids, plasma exchange, and chemotherapy agents.

PMID- 17445503
TI  - Dual probe with fluorescent and magnetic properties for imaging solid tumor
      xenografts.
AB  - A dual probe with fluorescent and magnetic reporter groups was constructed by
      linkage of the near-infrared (NIR) fluorescent transferrin conjugate (Tf(NIR)) on
      the surface of contrast agent-encapsulated cationic liposome (Lip-CA). This probe
      was used for magnetic resonance imaging (MRI) and optical imaging of MDA-MB-231
      luc breast cancer cells grown as a monolayer in vitro and as solid tumor
      xenografts in nude mice. Confocal microscopy, optical imaging, and MRI showed a
      dramatic increase of in vitro cellular uptake of the fluorescent and magnetic
      reporter groups from the probe compared with the uptake of contrast agent or Lip
      CA alone. Pretreatment with transferrin (Tf) blocked uptake of the probe
      reporters, indicating the importance and specificity of the Tf moiety for
      targeting. Intravenous administration of the dual probe to nude mice
      significantly enhanced the tumor contrast in MRI, and preferential accumulation
      of the fluorescent signal was clearly seen in NIR-based optical images. More
      interestingly, the contrast enhancement in MRI showed a heterogeneous pattern
      within tumors, which reflected the tumor's morphologic heterogeneity. These
      results indicate that the newly developed dual probe enhances the tumor image
      contrast and is superior to contrast agent alone for identifying the tumor
      pathologic features on the basis of MRI but also is suitable for NIR-based
      optical imaging.

PMID- 17445502
TI  - Inflammation-specific T1 imaging using anti-intercellular adhesion molecule 1
      antibody-conjugated gadolinium diethylenetriaminepentaacetic acid.
AB  - To examine inflammatory tissue, an initial and common symptom of various types of
      pathogenesis, we designed inflammation-targeted T(1) contrast agents prepared by
      bioconjugation of gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) with
      anti-intercellular adhesion molecule 1 (ICAM-1) antibody. The anti-ICAM-1
      antibody was coupled with DTPA and was then conjugated with Gd. The specific
      binding of the Gd-DTPA-anti-ICAM-1 antibody complex to the ICAM-1-expressing
      cells was examined in the cultured endothelial cells where ICAM-1 expression was
      stimulated. Inflammation-specific T(1) imaging was then assessed using a mouse
      abscess model with the 1.5-Tesla module. The Gd-DTPA-anti-ICAM-1 antibody
      displayed increased r1, which was two times higher than that of Gd-DTPA and
      showed predominant binding to cultured endothelial cells, which expressed a high
      level of ICAM-1. Moreover, the inflammation-specific T(1) enhancement was imaged
      with the Gd-DTPA-anti-ICAM-1 antibody in the mouse acute inflammation model. The
      Gd-DTPA-anti-ICAM-1 antibody showed significantly increased vascular circulation
      time, which thereby offered a greater chance for its binding to the target cells.
      The Gd-DTPA-anti-ICAM-1 antibody displays a potential targeted T(1) contrast
      agent specific to the inflammatory tissue that expresses ICAM-1.

PMID- 17445504
TI  - Three-dimensional in vivo imaging of green fluorescent protein-expressing T cells
      in mice with noncontact fluorescence molecular tomography.
AB  - Given that optical tomography is capable of quantitatively imaging the
      distribution of several important chromophores and fluorophores in vivo, there
      has been a great deal of interest in developing optical imaging systems with
      increased numbers of measurements under optimal experimental conditions. In this
      article, we present a novel system that enables three-dimensional imaging of
      fluorescent probes in whole animals using a noncontact setup, in parallel with a
      three-dimensional surface reconstruction algorithm. This approach is directed
      toward the in vivo imaging of fluorophore or fluorescent protein concentration in
      small animals. The system consists of a rotating sample holder and a lens-coupled
      charge-coupled device camera in combination with a fiber-coupled laser scanning
      device. By measuring multiple projections, large data sets can be obtained, thus
      improving the accuracy of the inversion models used for quantitative three
      dimensional reconstruction of fluorochrome distribution, as well as facilitating
      a higher spatial resolution. In this study, the system was applied to determining
      the distribution of green fluorescent protein (GFP)-expressing T lymphocytes in a
      transgenic mouse model, thus demonstrating the potential of the system for
      studying immune system function. The technique was used to image and reconstruct
      fluorescence originating from 32 x 10(6) T cells in the thymus and 3 x 10(5) T
      cells in the spleen.

PMID- 17445505
TI  - Multimodality registration without a dedicated multimodality scanner.
AB  - Multimodality scanners that allow the acquisition of both functional and
      structural image sets on a single system have recently become available for
      animal research use. Although the resultant registered functional/structural
      image sets can greatly enhance the interpretability of the functional data, the
      cost of multimodality systems can be prohibitive, and they are often limited to
      two modalities, which generally do not include magnetic resonance imaging. Using
      a thin plastic wrap to immobilize and fix a mouse or other small animal atop a
      removable bed, we are able to calculate registrations between all combinations of
      four different small animal imaging scanners (positron emission tomography,
      single-photon emission computed tomography, magnetic resonance, and computed
      tomography [CT]) at our disposal, effectively equivalent to a quadruple-modality
      scanner. A comparison of serially acquired CT images, with intervening
      acquisitions on other scanners, demonstrates the ability of the proposed
      procedures to maintain the rigidity of an anesthetized mouse during transport
      between scanners. Movement of the bony structures of the mouse was estimated to
      be 0.62 mm. Soft tissue movement was predominantly the result of the filling (or
      emptying) of the urinary bladder and thus largely constrained to this region.
      Phantom studies estimate the registration errors for all registration types to be
      less than 0.5 mm. Functional images using tracers targeted to known structures
      verify the accuracy of the functional to structural registrations. The procedures
      are easy to perform and produce robust and accurate results that rival those of
      dedicated multimodality scanners, but with more flexible registration
      combinations and while avoiding the expense and redundancy of multimodality
      systems.

PMID- 17445506
TI  - Continuous delivery of D-luciferin by implanted micro-osmotic pumps enables true
      real-time bioluminescence imaging of luciferase activity in vivo.
AB  - Bioluminescence imaging (BLI) of luciferase reporters in small animal models
      offers an attractive approach to monitor regulation of gene expression, signal
      transduction, and protein-protein interactions, as well as following tumor
      progression, cell engraftment, infectious pathogens, and target-specific drug
      action. Conventional BLI can be repeated within the same animal after bolus
      reinjections of a bioluminescent substrate. However, intervals between image
      acquisitions are governed by substrate pharmacokinetics and excretion, therefore
      restricting temporal resolution of reinjection protocols to the order of hours,
      limiting analyses of processes in vivo with short time constants. To eliminate
      these constraints, we examined use of implanted micro-osmotic pumps for
      continuous, long-term delivery of bioluminescent substrates. Pump-assisted d
      luciferin delivery enabled BLI for > or = 7 days from a variety of luciferase
      reporters. Pumps allowed direct repetitive imaging at < 5-minute intervals of the
      pharmacodynamics of proteasome- and IKK-inhibiting drugs in mice bearing tumors
      stably expressing ubiquitin-firefly luciferase or IkappaBalpha-firefly luciferase
      fusion reporters. Circadian oscillations in the olfactory bulbs of transgenic
      rats expressing firefly luciferase under the control of the period1 promoter also
      were temporally resolved over the course of several days. We conclude that
      implanted pumps provide reliable, prolonged substrate delivery for high temporal
      resolution BLI, traversing complications of repetitive substrate injections.

PMID- 17445507
TI  - Radiolabeled anti-claudin 4 and anti-prostate stem cell antigen: initial imaging
      in experimental models of pancreatic cancer.
AB  - Global expression profiling of pancreatic cancers has identified two cell surface
      molecules, claudin 4 and prostate stem cell antigen (PSCA), as being
      overexpressed in the vast majority of cases. Two antibodies, anti-claudin 4 and
      anti-PSCA, were radiolabeled with iodine 125 ((125)I) for imaging pancreatic
      cancer xenografts in mice using gamma scintigraphy and single-photon emission
      computed tomography-computed tomography (SPECT-CT). Immunofluorescence staining
      of intact and permeabilized Colo357 human pancreatic cancer cells showed strong
      extracellular staining by both anti-PSCA and anti-claudin 4. Biodistribution
      studies in claudin 4 and PSCA-expressing Colo357 and PANC-1 subcutaneous
      xenograft models in mice showed that [(125)I]anti-claudin 4 tumor to muscle ratio
      uptake was 4.3 in Colo357 at 6 days postinjection and 6.3 in PANC-1 xenografts at
      4 days postinjection. Biodistribution of [(125)I]anti-PSCA showed tumor to muscle
      ratio uptake of 4.9 in Colo357 at 6 days postinjection. Planar gamma
      scintigraphic imaging in Colo357 xenograft-bearing mice showed clear tumor uptake
      of [(125)I]anti-claudin 4 by 24 hours postinjection and by 48 hours postinjection
      for [(125)I]anti-PSCA. SPECT-CT imaging with [(125)I]anti-claudin 4 and
      [(125)I]anti-PSCA in an L3.6PL orthotopic xenograft model showed strong tumor and
      spleen uptake at 5 days postinjection. Both anti-claudin 4 and anti-PSCA
      demonstrate promise as radiodiagnostic and possibly radiotherapeutic agents for
      human pancreatic cancers.

PMID- 17445509
TI  - Problem formulation and hypothesis testing for environmental risk assessments of
      genetically modified crops.
AB  - Environmental risk assessments can provide high confidence of minimal risk by
      testing theories, "risk hypotheses", that predict the likelihood of unacceptable
      harmful events. The creation of risk hypotheses and a plan to test them is called
      problem formulation. Effective problem formulation seeks to maximize the
      possibility of detecting effects that indicate potential risk; if such effects
      are not detected, minimal risk is indicated with high confidence. Two important
      implications are that artificial test conditions can increase confidence, whereas
      prescriptive data requirements can reduce confidence (increase uncertainty) if
      they constrain problem formulation. Poor problem formulation can increase
      environmental risk because it leads to the collection of superfluous data that
      may delay or prevent the introduction of environmentally beneficial products.

PMID- 17445508
TI  - Magnetic targeting of rhodamine-labeled superparamagnetic liposomes to solid
      tumors: in vivo tracking by fibered confocal fluorescence microscopy.
AB  - Polyethylene glycol (PEG)ylated and rhodamine-labeled liposomes loaded with
      maghemite nanocrystals provide a novel nanoscaled hybrid system for magnetic
      targeting to solid tumors in possible combination with double in vivo imaging by
      fluorescence microscopy and magnetic resonance imaging (MRI). Human prostate
      adenocarcinoma tumors implanted in mice were used as a system model. A magnetic
      field gradient was produced at the tumor level by external apposition of a
      magnet. Noninvasive fibered confocal fluorescence microscopy was successfully
      used to track the liposomes in vivo within organs and tumor blood vessels. Active
      targeting to the magnet-exposed tumors was clearly shown, in agreement with
      previous MRI studies. The liposomes were driven and accumulated within the
      microvasculature through a process that preserved vesicle structure and content.

PMID- 17445510
TI  - The interplay between societal concerns and the regulatory frame on GM crops in
      the European Union.
AB  - Recapitulating how genetic modification technology and its agro-food products
      aroused strong societal opposition in the European Union, this paper demonstrates
      how this opposition contributed to shape the European regulatory frame on GM
      crops. More specifically, it describes how this opposition contributed to a de
      facto moratorium on the commercialization of new GM crop events in the end of the
      nineties. From this period onwards, the regulatory frame has been continuously
      revised in order to slow down further erosion of public and market confidence.
      Various scientific and technical reforms were made to meet societal concerns
      relating to the safety of GM crops. In this context, the precautionary principle,
      environmental post-market monitoring and traceability were adopted as ways to
      cope with scientific uncertainties. Labeling, traceability, co-existence and
      public information were installed in an attempt to meet the general public
      request for more information about GM agro-food products, and the specific demand
      to respect the consumers' and farmers' freedom of choice. Despite these efforts,
      today, the explicit role of public participation and/or ethical consultation
      during authorization procedures is at best minimal. Moreover, no legal room was
      created to progress to an integral sustainability evaluation during market
      procedures. It remains to be seen whether the recent policy shift towards greater
      transparency about value judgments, plural viewpoints and scientific
      uncertainties will be one step forward in integrating ethical concerns more
      explicitly in risk analysis. As such, the regulatory frame stands open for
      further interpretation, reflecting in various degrees a continued interplay with
      societal concerns relating to GM agro-food products. In this regard, both
      societal concerns and diversely interpreted regulatory criteria can be inferred
      as signaling a request - and even a quest - to render more explicit the broader
      than-scientific dimension of the actual risk analysis.

PMID- 17445511
TI  - Meteorological input data requirements to predict cross-pollination of GMO maize
      with Lagrangian approaches.
AB  - Modeling pollen dispersal to predict cross-pollination is of great importance for
      the ongoing discussion of adventitious presence of genetically modified material
      in food and feed. Two different modeling approaches for pollen dispersal were
      used to simulate two years of data for the rate of cross-pollination of non-GM
      maize (Zea mays (L.)) fields by pollen from a central 1 ha transgenic field. The
      models combine the processes of wind pollen dispersal (transport) and pollen
      competition. Both models used for the simulation of pollen dispersal were
      Lagrangian approaches: a stochastic particle Lagrange model and a Lagrangian
      transfer function model. Both modeling approaches proved to be appropriate for
      the simulation of the cross-pollination rates. However, model performance
      differed significantly between years. We considered different complexity in
      meteorological input data. Predictions compare well with experimental results for
      all simplification steps, except that systematic deviations occurred when only
      main wind direction was used. Concluding, it can be pointed out that both models
      might be adapted to other pollen dispersal experiments of different crops and
      plot sizes, when wind direction statistics are available. However, calibration of
      certain model parameters is necessary.

PMID- 17445512
TI  - Gene flow from GM glyphosate-tolerant to conventional soybeans under field
      conditions in Japan.
AB  - Natural out-crossing rates were evaluated for conventional soybeans (Glycine max
      (L.) Merr.) cultivated adjacent to genetically modified (GM) glyphosate-tolerant
      soybeans under field conditions during a four-year period in Japan. A total of
      107 846 progeny of 2772 plants harvested from conventional varieties were
      screened for glyphosate herbicide tolerance. The highest out-crossing rates,
      0.19% in 2001 and 0.16% in 2002, were observed in adjacent rows 0.7 m from the
      pollen source. The highest rate in 2004 was 0.052%, which was observed at 2.1 m.
      No out-crossing was observed in the rows 10.5 m from the pollen source over the
      four-year period. The farthest distances between receptor and pollen source at
      which out-crossing was observed were 7 m in 2001, 2.8 m in 2002, and 3.5 m in
      2004. The greatest airborne pollen density during the flowering period,
      determined by Durham pollen samplers located between the rows of each variety,
      was 0.368 grains.cm(-2).day(-1), with the average value at 0.18 grains.cm(
      2).day(-1), indicating that the possibility of out-crossing by wind is minimal.
      Thrips species and predatory Hemiptera visited the soybean flowers more
      frequently during the four-year period than any other common pollinators, such as
      bees.

PMID- 17445513
TI  - Is unipolar mania a distinct subtype?
AB  - BACKGROUND: Some recent reports raised the question whether unipolar mania,
      without severe or mild depression, really exists and whether it defines a
      distinct disorder. Literature on this topic is still scarce, although this was a
      matter of debate since several decades. METHOD: Eighty-seven inpatients with
      Diagnostic and Statistical Manual of Mental Disorder, Revised Third Edition,
      manic episode and at least 3 major affective episodes, in 10 years of illness
      duration, were systematically evaluated to collect demographic and clinical
      information. The symptomatological evaluation was conducted by means of the
      Comprehensive Psychopathological Rating Scale. Clinical features, social
      disability, first-degree family history, and temperaments were compared between
      unipolar and bipolar manics. RESULTS: Nineteen (21.8%) of 87 patients presented a
      course of illness characterized by recurrent unipolar manic episodes without
      history of major or mild depression (MAN). When this group was compared with 68
      (78.2%) manic patients with a previous history of depressive episodes (BIP), we
      found substantial similarities in most demographic, familial, and clinical
      characteristics. MAN group reported more congruent psychotic symptoms and more
      frequent chronic course of the current episode in comparison to BIP group. In the
      MAN patients, we also observed a high percentage of hyperthymic temperament and a
      complete absence of depressive temperament. This latter difference was
      statistically significant. MAN patients compared with BIP ones also reported
      lower severity scores in social, familial, and work disability, and they showed
      less depressive features, hostility, and anxiety. CONCLUSION: The numerous
      demographic, clinical, and psychopathological overlapping characteristics in
      unipolar and bipolar mania raise questions about the general nosographic utility
      of this categorization. Nonetheless, our data suggest a clinical and prognostic
      validity of keeping unipolar manic patients as a separate subgroup, in
      particular, as social adjustment and disability are concerned.

PMID- 17445514
TI  - Eating disorders and suicide ideation: the mediating role of depression and
      aggressiveness.
AB  - OBJECTIVE: Symptoms of depression and aggressiveness are important antecedents
      and correlates of suicide ideation and completion in adolescents and adults.
      Among adolescents, eating disorder symptoms were also found to associate with
      suicidal behavior. This study was aimed at investigating the role of depression
      and aggressiveness as mediators in the links between eating disorder symptoms and
      suicide ideation among adolescents, taking into account age and sex as
      covariates. METHOD: Data from the Conegliano Eating Disorders Survey were used to
      investigate the role of depression and aggressiveness in the links between eating
      disorder symptoms and suicide ideation, resorting to a bootstrapped sampling
      distribution model. RESULTS: In a mixed male-female sample of 930 adolescents,
      eating disorder symptoms were positively related to suicide ideation, taking age
      and sex into account. Depression and aggressiveness acted as full mediators in
      the links between eating disorder symptoms and suicidality, and virtually
      abolished any direct influence of eating disorders on suicide ideation.
      CONCLUSION: Because of the cross-sectional nature of this study and the resorting
      to self-report scales, no firm statement about causal association can be made.
      However, both suicidal behavior and eating disorder symptoms are a rather
      widespread occurrence among adolescents, hence the investigation on suicidal
      tendencies in young people might benefit from the inclusion of measures of eating
      disorders to prevent the worst outcomes of minor psychological distress.

PMID- 17445515
TI  - An empirical study of countertransference reactions toward patients with
      personality disorders.
AB  - OBJECTIVE: The study examined to what extent patients with cluster A + B
      personality disorders (PDs) evoked other countertransference reactions among
      psychotherapists compared with patients with cluster C PDs as well as the
      relationship between the different countertransference reactions and outcome.
      METHODS: A total of 11 therapists at the Department for Personality Psychiatry,
      Ullevaal University Hospital, Oslo, Norway, filled out the Feeling Word Checklist
      58 (FWC-58), 2 weeks after admission and 2 weeks before discharge, for 71
      patients admitted to the day treatment program. The patients were diagnosed with
      the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II).
      RESULTS: The study revealed that patients with cluster A + B PDs evoked more
      negative and less positive countertransference reactions than those with cluster
      C PDs. The psychotherapists varied significantly more in their reported
      countertransference reactions toward patients with cluster A + B PDs than toward
      those with cluster C PDs. Patients who dropped out of treatment evoked
      significantly more negative countertransference reactions after 2 weeks than
      patients who completed the treatment. In addition, the study revealed strong
      correlations between countertransference feelings and change during the
      treatment. CONCLUSIONS: This empirical study confirms clinical narratives on
      specified relationships between countertransference reactions, different PDs, and
      treatment course.

PMID- 17445516
TI  - The prognostic significance of depressive symptoms for predicting quality of life
      12 months after gastric bypass.
AB  - OBJECTIVE: This study was conducted to examine the relative prognostic
      significance of weight and depressive symptoms for 12-month postoperative health
      related quality of life (HRQL) in extremely obese gastric bypass patients.
      METHODS: Participants comprised 137 extremely obese patients undergoing gastric
      bypass surgery. Presurgery and 12 months postsurgery participants completed the
      Medical Outcomes Study Short Form-36 Health Survey, a standard measure of HRQL,
      and the Beck Depression Inventory (BDI). Regression analyses were performed to
      predict HRQL, both before and 12 months after surgery, by using demographic
      variables, and measures of body mass index (BMI) and depressive symptoms as
      predictors. RESULTS: At baseline the predictors accounted for 19% of the variance
      of physical HRQL, and 56% of the variance of mental HRQL. At 12 months after
      surgery, the predictors accounted for 32% of the variance of physical HRQL and
      48% of mental HRQL. In the prediction of 12-month postoperative HRQL, baseline
      BMI, BMI unit change, baseline BDI, and improvements in BDI score made
      significant contributions to most of the Medical Outcomes Study Short Form-36
      Health Survey scales. Demography contributed little to these predictor analyses.
      Depressive symptoms made greater contributions than weight and demography, and
      change in BDI score made the greatest contributions (ranging from 3% to 37%) of
      all the variables tested. CONCLUSIONS: Measures of weight and depressive symptoms
      were useful in predicting quality of life both before and 12 months after gastric
      bypass surgery; however, this is the first study to document that improvements in
      HRQL postsurgery may be largely related to improved depressive symptoms.

PMID- 17445518
TI  - Bipolar and nonbipolar obsessive-compulsive disorder: a clinical exploration.
AB  - Comorbidity of obsessive-compulsive disorder (OCD) in bipolar disorder is well
      documented. However, clinical characteristics of bipolar OCD are not well
      studied. The objective of the present study was to compare the clinical
      characteristics of bipolar and nonbipolar OCD. We chose 28 subjects with bipolar
      OCD comorbidity from a sample of 80 remitted bipolar subjects (bipolar OCD)
      attending the outpatient services of the National Institute of Mental Health and
      Neurosciences, Bangalore, India, over a period of 11 months. We also recruited 78
      nonbipolar OCD subjects consecutively during the same period from the OCD clinic
      of the institute. They underwent systematic assessment using both structured and
      unstructured clinical interviews and corroborative information obtained from the
      immediate family members and the hospital clinical charts. Bipolar OCD subjects
      were characterized by episodic course of OCD, high family loading for mood
      disorders, and comorbidity with depression, social phobia, and generalized
      anxiety disorder. They had less severe OCD and had somewhat different symptom
      profile compared with nonbipolar OCD. The OCD predated bipolar disorder in 54% of
      the bipolar OCD subjects; and in the remaining subjects, it had an onset during
      the course of bipolar disorder. Most bipolar OCD subjects reported worsening of
      OCD in depression (n = 22, 78%) and improvement in manic/hypomanic episodes (n =
      18, 64%). Our findings suggest that OCD in those with a primary diagnosis of
      bipolar disorder is perhaps pathophysiologically related to bipolar disorder than
      to OCD. This is strongly supported by the episodic course of OCD, high familial
      loading for mood disorders, and worsening of OCD in depression with improvement
      in hypomania/mania phases. There is a need for systematic exploration of the OCD
      bipolar comorbidity in both OCD and bipolar samples. Family-genetic and other
      neurobiological research and the prospective follow-up of bipolar and nonbipolar
      OCD subjects would further enhance our understanding of this complex comorbidity.
      The cross-sectional nature of the study based on retrospective assessment of
      course, the small sample size and the inclusion of only remitted bipolar subjects
      are the limitations of this study.

PMID- 17445517
TI  - Association between psychiatric disorders and smoking stages within a
      representative clinic sample of Puerto Rican adolescents.
AB  - OBJECTIVE: We examined the prevalence of smoking behaviors and their association
      with specific psychiatric disorders in a representative sample of youth from
      behavioral health clinics in Puerto Rico. METHOD: A complex sampling design was
      used to select the sample, and analyses were conducted to account for the unequal
      selection probability, stratification, and clustering. All analyses were weighted
      back to the clinical population from which they were drawn. Psychiatric and
      substance use disorders were assessed using the parent and youth versions of the
      Diagnostic Interview Schedule for Children, Version 4.0. RESULTS: More than one
      third of the sample reported experience with cigarette smoking, and approximately
      one quarter reported smoking at least once per week (23.4%). As expected, the
      alcohol and drug use disorders demonstrated some of the strongest associations
      with individual smoking stages. These were the only disorders that remained
      significantly associated with nicotine dependence after controlling for
      comorbidity. CONCLUSIONS: Our findings confirm the need for screening of smoking
      behavior and nicotine dependence in treatment settings and the integration of
      psychiatric/substance use treatments with smoking cessation.

PMID- 17445519
TI  - "Excessive tears": a diagnostic sign for cocaine-induced mood disorder?
AB  - OBJECTIVE: This study aims to investigate excessive tearfulness as a sign to help
      determine the etiology of depressive symptoms. METHODS: Clinicians were
      instructed to document the occurrence of excessive tearfulness in all patients
      seen in the Psychiatric Emergency Service. Excessive tearfulness was defined as
      crying to the severity that at least 1 tear drops off the face. A comparison
      group was formed from the general population of the Psychiatric Emergency
      Service. RESULTS: Excessive tearfulness was documented in 36 different patients.
      The prevalence of the sign in the general population was 1.9%. Patients with
      excessive tearfulness were more likely to have cocaine in their urine (P < .0001,
      chi(2) test), receive a substance-related primary diagnosis (P < .0001, chi(2)
      test), and be admitted for psychiatric hospitalization (P < .001 chi(2) test).
      Patients with excessive tearfulness had significantly shorter voluntary hospital
      stays (P < .05, t test). CONCLUSION: Excessive tearfulness could be a useful
      clinical sign of cocaine-induced depression.

PMID- 17445520
TI  - Caffeine challenge test in panic disorder and depression with panic attacks.
AB  - Our aim was to observe if patients with panic disorder (PD) and patients with
      major depression with panic attacks (MDP) (Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition criteria) respond in a similar way to the
      induction of panic attacks by an oral caffeine challenge test. We randomly
      selected 29 patients with PD, 27 with MDP, 25 with major depression without panic
      attacks (MD), and 28 healthy volunteers. The patients had no psychotropic drug
      for at least a 4-week period. In a randomized double-blind experiment performed
      in 2 occasions 7 days apart, 480 mg caffeine and a caffeine-free (placebo)
      solution were administered in a coffee form and anxiety scales were applied
      before and after each test. A total of 58.6% (n = 17) of patients with PD, 44.4%
      (n = 12) of patients with MDP, 12.0% (n = 3) of patients with MD, and 7.1% (n= 2)
      of control subjects had a panic attack after the 480-mg caffeine challenge test
      (chi(2)(3) = 16.22, P = .001). The patients with PD and MDP were more sensitive
      to caffeine than were patients with MD and healthy volunteers. No panic attack
      was observed after the caffeine-free solution intake. The patients with MD had a
      lower heart rate response to the test than all the other groups (2-way analysis
      of variance, group by time interaction with Greenhouse-Geisser correction:
      F(3,762) = 2.85, P = .026). Our data suggest that there is an association between
      panic attacks, no matter if associated with PD or MDP, and hyperreactivity to an
      oral caffeine challenge test.

PMID- 17445521
TI  - Insight and psychopathology in never-treated schizophrenia.
AB  - Insight is a feature of schizophrenia related to psychopathology, which could be
      modified by treatment. The real relationship will be more evident in the never
      treated state. This study compared insight and its relationship to
      psychopathology in 143 never-treated patients with chronic schizophrenia with 183
      treated patients. The treated patients had not received any structured
      intervention for improvement of insight. The item on insight and judgment from
      the Positive and Negative Syndrome Scale for schizophrenia was used as a measure
      of insight. Never-treated patients were more ill and poorer in insight than the
      TT group. Sex, age, duration of illness, negative symptoms related to insight
      only in the TT group. Positive symptoms score correlated with insight in both the
      groups, but negative symptoms correlated with insight only among the treated
      patients. Delusions, uncooperativeness, and poor attention predicted 27% of
      variation in the level of insight in the never-treated, whereas age; duration of
      illness; and symptoms of emotional withdrawal, difficulty in abstract thinking,
      and uncooperativeness predicted 30.3% of variation in insight of the TT group.
      The observed differences between the never-treated and treated subjects were due
      to influence of treatment on the association between insight and psychopathology.
      A subgroup of patients with a treatment-resistant trait of negative symptoms
      associated with poor insight was hypothesized.

PMID- 17445522
TI  - Long-term psychological outcome of 1999 Taiwan earthquake survivors: a survey of
      a high-risk sample with property damage.
AB  - OBJECTIVE: Severe natural disasters can cause long-term psychological impact on
      the survivors. This study aimed to examine the prevalence and risk factors of
      posttraumatic stress symptoms and psychiatric morbidity among survivors of the
      severe earthquake that occurred in Chi-Chi, Taiwan, in September 21, 1999.
      METHODS: A total of 6412 earthquake survivors whose houses were destroyed by
      earthquake were recruited about 2 years after the disaster. They completed a self
      report questionnaire assessing posttraumatic stress symptoms, psychiatric
      morbidity, and information of demographics, trauma exposure, and current living
      status. RESULTS: The estimated rates of posttraumatic stress disorder caseness
      and psychiatric morbidity were 20.9% and 39.8%, respectively. Psychiatric
      morbidity occurred mainly in survivors who were female, older, with low education
      level, and currently living in a prefabricated house. The risk factors for
      posttraumatic stress disorder caseness were female sex, currently living in a
      prefabricated house, low education level, and experienced complete destruction of
      property. CONCLUSION: These results showed that severe earthquake can cause long
      term psychological impact in the survivors. The findings of risk factors suggest
      avenues for targeting postdisaster interventions.

PMID- 17445523
TI  - Intellectual functioning and memory deficits in schizophrenia.
AB  - BACKGROUND: There is converging evidence about the existence of different
      subgroups of patients with schizophrenia in relation to intellectual ability
      (intelligence quotient [IQ]). Studying cognitive deficits in such patients in
      relation to IQ, and more specifically to memory, could help determine the
      patterns of preserved and impaired functioning in cognitive abilities in
      association with patterns of preserved and compromised intellect. This
      information could serve to delimit the possibilities of treatment and
      rehabilitation in those patients. METHODS: A total of 44 patients with
      schizophrenia completed a cognitive battery that included executive functioning,
      attention, speed of information processing, working memory, explicit memory,
      implicit memory, and everyday memory. Their IQ was also measured to identify 2
      subgroups with an IQ of 85 as the cutoff point. Then, differences between the
      groups in the neurocognitive measures were studied. RESULTS: Performance in
      executive functioning, attention, working memory, and everyday memory, but not
      that in speed of information processing, explicit memory, and implicit memory,
      was associated with intellectual functioning. Patients performed at the same
      level in perceptual implicit memory but at a lower level in conceptual implicit
      memory as did healthy control subjects. DISCUSSION: Cognitive deficits in
      schizophrenia are associated with intellectual functioning. Implicit memory
      should not be considered as a unique entity. It is suggested that conceptual
      implicit memory deficit may be a core feature of schizophrenia.

PMID- 17445524
TI  - Temperament and character model of personality profile of alcohol- and drug
      dependent inpatients.
AB  - The aims of this study were to evaluate the differences in dimensions of
      temperament and character in Turkish alcohol- and drug-dependent inpatients, and
      to examine which dimensions would predict drug dependency. The subjects consisted
      of 111 alcohol-dependent and 93 drug-dependent inpatients according to the
      Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Subjects were
      tested using Cloninger's Temperament and Character Inventory (TCI). Among the
      temperament dimensions, novelty seeking score was higher and reward dependency
      score was lower in drug-dependent patients than in alcohol-dependent patients.
      Among the character dimensions, self-directedness and cooperativeness scores were
      lower in drug-dependent patients. Low age and novelty seeking predicted drug
      dependency in forward logistic regression model. Subscales that predicted drug
      dependency other than young age were lower scores on compassion vs revengefulness
      (C4) and helpfulness (C3), and higher score on spiritual acceptance vs rational
      materialism (ST3). As in previous studies, which indicate an association between
      personality and substance choice, in the present study, TCI was shown to be an
      efficient tool in discriminating alcohol and drug dependents; thus, it seems to
      be important to consider TCI dimensions in planning the treatment of substance
      dependency.

PMID- 17445525
TI  - Reliability and validity of the Japanese version of the Anxiety Sensitivity
      Index.
AB  - This preliminary study evaluated the reliability and validity of the Japanese
      version of the Anxiety Sensitivity Index (ASI). Its test-retest reliability and
      internal consistency were found acceptable. Factor analysis of the ASI yielded 4
      anxiety-related factors: factor I is heart/lung failure concern; factor II,
      psychological concern; factor III, physical concern; and factor IV, social
      concern. In addition, multiple regression analysis showed that the ASI score
      significantly correlated only with the neuroticism-related category of the NEO
      Personality Inventory Revised. The ASI mean scores of those with 5 or more
      according to the General Health Questionnaire (unhealthy) and those with 16 or
      more according to the Center for Epidemiological Studies Depressive Scale
      (depression) were significantly higher than in the healthy and nondepressive
      groups. Although further research is necessary to confirm the construct validity
      by factor analysis of the ASI, the Japanese version of the ASI is applicable for
      use in the Japanese population.

PMID- 17445526
TI  - Neuropsychological and activity of daily living script performance in patients
      with positive or negative schizophrenia.
AB  - Cognitive and psychiatric determinants of impairment of complex activities of
      daily living (ADLs) were investigated in 33 schizophrenic patients and 16 normal
      comparison subjects. The schizophrenic patients were cognitively impaired and
      were deficient in the ADL. However, the impairment of ADL could not be explained
      specifically by impairment of higher-order executive function or by negative
      symptoms: memory functions were more related to impairment of ADL and positive
      symptoms as much as the negative ones. Positive symptoms were significantly
      related to commissive errors in the ADL, whereas negative symptoms were
      nonsignificantly related to omissive errors. Negative symptoms were significantly
      more related to memory impairment than to impairment on measures of higher-order
      executive function (working memory). This investigation demonstrates that an
      ecologically oriented approach to test development and measurement of ADL is
      fruitful in understanding schizophrenia-especially if it is constrained by
      cognitive constructs compatible with the phenomenology of the disease.

PMID- 17445527
TI  - Harm avoidance, self-harm, psychic pain, and the borderline personality: life in
      a "haunted house".
AB  - This article investigates the pattern of temperament for patients with borderline
      personality disorder and the impact of psychotherapeutic treatment on
      temperamental variables. A cohort of patients treated in the Westmead Borderline
      Personality Disorder Psychotherapy research project completed the Tridimensional
      Personality Questionnaire. All patients had a diagnosis of borderline personality
      disorder according to the Diagnostic and Statistical Manual of Mental Disorders,
      Revised Third Edition, criteria. This group scored highly on novelty-seeking and
      harm avoidance scales and moderately on reward dependence. There was a
      significant reduction in harm avoidance after 12 months of psychotherapy with a
      further reduction after 2 years in therapy. Although at variance with Cloninger's
      original prediction of low harm avoidance in histrionic and borderline patients,
      results are consistent with other studies in this patient group. The paradox of
      "self-harmers" scoring highly on harm avoidance may be explained by recognition
      of the intensity of "psychic pain" in this group. Self-harming behaviors may
      frequently be motivated by avoidance of a "greater harm" in terms of the inner
      psychic reality for these patients. Reduction in harm avoidance with
      psychotherapy could suggest an impact of treatment on temperament or may indicate
      that the harm avoidance construct is influenced by state variables such as mood.

PMID- 17445528
TI  - Evolution of pelvic and acetabular surgery from ancient to modern times.
AB  - Fracture stabilisation before the 19th century was in its infancy. The outcome
      was suboptimal, and quite often mortality was the end result. Advances in the
      stabilisation of long-bone fractures did not become apparent until the mid-1940s
      and for other bones, even later. In the mid-1960s, Judet and Letournel initiated
      a series of experimental and clinical studies focusing on pelvic and acetabular
      reconstruction surgery. Their work set the pace for all the subsequent
      advancements made in this field of surgery. Today, pelvic and acetabular
      reconstruction is a recognised subspecialty within the disciplines of trauma and
      orthopaedics. This review article traces the evolution of pelvic and acetabular
      surgery, from ancient to modern times.

PMID- 17445529
TI  - Modified and new approaches for pelvic and acetabular surgery.
AB  - We analysed outcomes of new operative techniques for open reduction and internal
      fixation in 120 consecutive patients with fractures of the pelvic ring and 164
      patients with acetabular fractures treated between 1989 and 1999. An anterior
      extraperitoneal approach was performed through a low midline incision to fix the
      anterior and lateral parts of the pelvis and for central involvement of different
      types of acetabular fractures. The anterior approach was combined with a lateral
      incision on the lateral crest for fractures of the iliac wing and with a
      posterior approach for sacroiliac injuries, or with Kocher-Langenbeck approach
      for posterior acetabular involvements. The complication rate of the new
      techniques was low. Heterotopic ossification was rare. The functional recovery
      was good in 66 of the 81 patients with an unstable C-type pelvic injury, in 18
      out of the 20 patients with a lateral compression, B-2-type injury and 13 out of
      19 patients with a open book, B-1-injury. Neurological recovery was observed
      after adequate reduction in those patients suffering from lesions of the sacral
      plexus. The radiographic result was good in 73, 20 and 17 of the patients groups,
      respectively. The Harris Hip Score was more than 80 in 75% of the 164 patients
      with an acetabular fracture. The radiological result was good (residual
      displacement 0-2mm) in 84%, fair (3-5mm) in 9% and poor (more than 5mm) in 7%.
      The new methods are less invasive than the basic approaches described in the
      literature. The whole pelvic ring, as well as all the acetabular fracture
      combinations may be treated with the combination of approaches used in the
      present study.

PMID- 17445530
TI  - '... And midwifery': time for a parting of the ways or a closer union with
      nursing?

PMID- 17445531
TI  - Protective effect against type 2 diabetes mellitus identified within the ACDC
      gene in a black South African diabetic cohort.
AB  - Type 2 diabetes mellitus (T2D) is currently one of the fastest growing
      noncommunicable diseases in the world. It is induced by the pathogenic
      interaction between insulin resistance and secretion. This group of clinically
      heterogeneous disorders currently affects approximately 4% of the general
      population, but it is rapidly increasing, especially in developing regions such
      as sub-Saharan Africa. During this investigation, a diabetic (n = 227) and
      control cohort (n = 226) of adult black South African individuals were screened
      for the reported single nucleotide polymorphisms, termed C-11377G and G-11391A,
      within the promoter of the adiponectin (ACDC) gene. Genotyping was achieved via a
      real-time polymerase chain reaction method. It was determined that the variant
      allele at G-11391A as well as the 12 haplotype was significantly associated with
      a protective factor with regard to T2D susceptibility. The low frequency of this
      variant within the cohorts investigated indicated a minor role in decreasing
      disease susceptibility. It may not be a significant disease risk factor in
      itself, but may assist in elucidating the mechanism of disease susceptibility.
      When compared to various non-African populations, it becomes apparent that the
      investigated single nucleotide polymorphisms have differential effects depending
      on the population investigated. This investigation therefore underscores the
      genetic heterogeneity at T2D susceptibility loci within the black South African
      population.

PMID- 17445532
TI  - Predictors for silent cerebral infarction in patients with chronic renal failure
      undergoing hemodialysis.
AB  - In patients with chronic renal failure undergoing hemodialysis (HD), silent
      cerebral infarctions (SCIs) are associated with high mortality. Levels of
      hepatocyte growth factor (HGF) increase with renal dysfunction and may be a novel
      predictor of cerebrovascular events. We examined if HGF is a predictor of SCI in
      HD patients. Brain magnetic resonance imaging findings were used to divide 50
      patients undergoing HD into 2 groups, a group with SCI (age, 61 +/- 8 years, mean
      +/- SD; n = 27) and a group without SCI (age, 60 +/- 7 years; n = 23). These
      patients received 24-hour ambulatory blood pressure monitoring. The number of
      patients with diabetes or hypertension was not different between the 2 groups. We
      made the following observations: (1) The percentage of smokers was higher in the
      group with SCI than in the group without SCI (P < .05). (2) Plasma levels of high
      density lipoprotein cholesterol were lower and HGF levels were higher in the
      group with SCI compared with the group without SCI (P < .05 and P < .005,
      respectively). (3) Systolic ambulatory blood pressure and mean heart rate at
      night were higher in the group with SCI than in the group without SCI (P < .05).
      Multiple logistic regression analysis identified HGF as a significant risk factor
      for SCI (odds ratio, 1.89; 95% confidence interval, 1.57-3.38; P < .005). Our
      findings indicate that HGF may be a novel useful predictor of SCI in patients
      with chronic renal failure undergoing HD.

PMID- 17445533
TI  - Long-term consumption of caffeine improves glucose homeostasis by enhancing
      insulinotropic action through islet insulin/insulin-like growth factor 1
      signaling in diabetic rats.
AB  - Our previous study demonstrated that long-term cola consumption reduced body
      weight and improved insulin sensitivity in healthy male rats. In this study, we
      investigated the effect and mechanism of caffeine and sucrose, major components
      of cola, on glucose metabolism in 90% pancreatectomized diabetic rats. After a 12
      week administration of 0.01% caffeine solution, the rats exhibited reduced body
      weight, fats, and insulin resistance, without a change in food intake, regardless
      of an 11% sucrose solution supplementation. In addition, caffeine enhanced
      glucose-stimulated first- and second-phase insulin secretion and beta-cell
      hyperplasia. This insulinotropic action was explained by potentiating an
      insulin/insulin-like growth factor 1 (IGF-1) signaling cascade via induction of
      insulin receptor substrate 2 in islets. In contrast, sucrose supplementation
      deteriorated insulin sensitivity and attenuated insulin/IGF-1 signaling in
      islets, which reduced the number of beta cells. Caffeine nullified the adverse
      effect of sucrose on glucose homeostasis. These findings indicate that long-term
      caffeine consumption can help alleviate diabetic symptoms by enhancing insulin
      sensitivity and beta-cell function through improved insulin/IGF-1 signaling via
      induction of insulin receptor substrate 2 in mildly diabetic rats.

PMID- 17445534
TI  - Impact of low-density lipoprotein particle size on carotid intima-media thickness
      in patients with type 2 diabetes mellitus.
AB  - Small low-density lipoprotein (LDL) particles and modifications to LDL such as
      glycation and oxidation have been linked to the pathogenesis of atherosclerosis
      in patients with diabetes. We investigated whether LDL particle size, or the
      levels of glycated LDL or malondialdehyde-modified LDL (MDA-LDL) are associated
      with carotid intima-media thickness (IMT) in patients with type 2 diabetes
      mellitus. One hundred seventy-two patients with type 2 diabetes mellitus were
      enrolled. Carotid IMT was measured by high-resolution ultrasound, and LDL
      particle size and serum glycated LDL and MDA-LDL levels were determined. The 3
      variables were significantly correlated with one another. Univariate analyses
      defined statistically significant correlations of carotid IMT with LDL size,
      hemoglobin A(1c), glycated LDL, MDA-LDL, high-density lipoprotein (HDL)
      cholesterol, and age. The strongest association of IMT was with LDL size (r = 
      0.406, P < .0001), followed by that with HDL cholesterol (r = -0.225, P = .004).
      A stepwise multiple regression analysis revealed that LDL size and HDL
      cholesterol are independent predictors of carotid IMT. Neither glycated LDL nor
      MDA-LDL had a significant independent contribution to the severity of carotid IMT
      in the multivariate model. Low-density lipoprotein particle size, but not the
      glycated LDL or MDA-LDL level, was independently associated with carotid IMT in
      patients with type 2 diabetes mellitus regardless of antidiabetic and lipid
      lowering medications. These results suggest that the measurement of LDL size may
      be more useful than quantification of modified LDLs for assessing atherosclerosis
      in patients with type 2 diabetes mellitus. Small LDL particles may be the most
      important predictor for the risk of cardiovascular disease in diabetic patients.

PMID- 17445535
TI  - Cardiovascular risk factor levels and their relationships with overweight and fat
      distribution in children: the Fleurbaix Laventie Ville Sante II study.
AB  - This study aimed to document for the first time in a general population of French
      children the prevalence and levels of cardiovascular risk factors and to assess
      separately in boys and girls whether these risk factors were associated with fat
      mass distribution independently of subcutaneous overall adiposity. A cross
      sectional analysis of baseline data from 452 children (235 boys and 217 girls)
      aged 8 to 17 years included in a 1999 population-based epidemiologic study (the
      Fleurbaix Laventie Ville Sante II study) was made. Overweight was defined
      according to the International Obesity Task Force references and the 90th
      percentiles of the French body mass index curves. The thresholds of parameters
      defining cardiovascular and metabolic risks were the 95th percentile of the Task
      Force Report on High Blood Pressure in Children and Adolescents for blood
      pressure and those of the American Academy of Pediatrics for lipids.
      Anthropometric and biological parameters were described by sex and according to
      overweight status. Partial correlations between cardiovascular risk factors and
      anthropometric measures of adiposity (body mass index, sum of 4 skinfold
      thicknesses, waist circumference, waist-to-height ratio) were calculated. Then,
      these correlations were additionally adjusted for the sum of 4 skinfold
      thicknesses. High plasma triglycerides, high insulin concentration, and low
      plasma high-density lipoprotein cholesterol (HDL-C) concentration were associated
      with all measures of adiposity (|r| > or = 0.20, P < .002). When obese children
      were excluded, overweight children already had high triglycerides and low HDL-C
      levels, respectively, 2 and 20 times more frequently than normal-weight children
      did. Among overweight children, 7.7% had at least 2 risk factors among high blood
      pressure, high plasma triglycerides or glucose, and low HDL-C concentration vs
      0.25% among normal-weight children (P = .002). After adjusting for the sum of
      skinfolds, an independent association between the risk factors and waist
      circumference was found in girls. In conclusion, (a) modest excess weight is
      associated with increased levels of cardiovascular risk factors. (b) In girls,
      abdominal fat distribution is associated with cardiovascular risk factors,
      independently of overall adiposity. (c) International definition of abdominal
      obesity in children is required to standardize studies and to progress in the
      evaluation of childhood obesity and its consequences.

PMID- 17445536
TI  - Serum leptin and adiponectin are positively associated with bone mineral density
      at the distal radius in patients with type 2 diabetes mellitus.
AB  - There have been several reports about associations of serum leptin or adiponectin
      with bone mineral density and biochemical markers of bone turnover. However, the
      precise roles of adipocytokines in bone metabolism have not been fully
      elucidated. We investigated the associations of serum level of leptin or
      adiponectin with bone mineral density, serum osteocalcin, and urinary N-terminal
      telopeptide of type I collagen (NTX) in 40 Japanese patients with type 2 diabetes
      mellitus. Bone mineral density was measured by using dual-energy x-ray
      absorptiometry at different sites (distal radius, femoral neck, and lumbar spine)
      and was expressed as z score. Multiple regression analysis revealed that there
      were significant positive correlations between serum leptin or adiponectin level
      and z score at the distal radius, but not at the femoral neck or the lumbar
      spine. Although no correlation was observed between serum leptin and serum
      osteocalcin, there was a significant negative correlation between serum leptin
      and urinary NTX, a marker of bone resorption. No correlation was observed between
      serum adiponectin and serum osteocalcin or urinary NTX. These results indicate
      that leptin and adiponectin may have a protective effect on bone metabolism in
      patients with type 2 diabetes mellitus.

PMID- 17445537
TI  - Hemostatic factors in Australian Aboriginal and Torres Strait Islander
      populations.
AB  - Hemostatic processes are important in precipitating myocardial infarction and
      stroke. Elevated plasma fibrinogen is considered a risk factor for cardiovascular
      diseases (CVDs), but the results of previous studies on the association of plasma
      factor VIIc activity with CVD and diabetes have been inconsistent. The aim of the
      present study was to explore the association of plasma fibrinogen and factor VIIc
      to clinical characteristics and estimated coronary heart disease (CHD) risk in
      Aboriginal and Torres Strait Islander peoples. Cross-sectional surveys of
      Australian Aboriginal people (n = 852) and Torres Strait Islanders (n = 276) aged
      15 years and older were conducted from 1993 to 1995. Anthropometric
      characteristics, blood pressure, fasting plasma fibrinogen, factor VIIc, total
      and high-density lipoprotein cholesterol, triglycerides, and glucose were
      measured. Levels of fibrinogen (mean, 95% confidence interval) for Aboriginal
      (3.52, 3.44-3.59 g/L) and Torres Strait Islander people (3.62, 3.49-3.75 g/L)
      were higher compared with previous reports from other populations. Factor VIIc
      (mean, 95% confidence interval) was especially high in Torres Strait Islanders
      (116%, 111%-122%) compared with Aboriginal people (99%, 97%-102%). Fibrinogen
      increased with age in both ethnic groups and sexes. Fibrinogen was independently
      associated with female sex, body mass index, renal dysfunction, low levels of
      high-density lipoprotein cholesterol and diabetes, whereas the independent
      predictors for factor VIIc were Torres Strait Islander ethnicity, female sex,
      body mass index, renal dysfunction, and total cholesterol. Average fibrinogen
      levels were high (>3.5 mg/dL) even for people considered "below average risk of
      coronary heart disease" according to conventional risk factor levels. For
      Aboriginal women, levels of fibrinogen and factor VIIc were significantly higher
      for persons at high risk than those at below average risk. The data suggest that
      plasma fibrinogen and factor VIIc might be important factors mediating the
      elevated CVD in Australian Indigenous Peoples. These data may have implications
      for prevention and treatment of CVD in Australian Indigenous communities.

PMID- 17445538
TI  - Two novel mutations 685del 1 and D129G in the low-density lipoprotein receptor
      gene in a compound heterozygote Chinese family with familial
      hypercholesterolemia.
AB  - DNA sequencing analysis was used to scan the genes in a Chinese family with
      clinically diagnosed autosomal genetic hypercholesterolemia. Two mutations were
      identified in exon 4 of the low-density lipoprotein receptor gene, which is the
      possible molecular mechanism of etiology of the family. The proband's extremely
      high level of serum cholesterol and the related manifestations suggested that he
      was a familial hypercholesterolemia homozygote and that his parents were in a
      relatively milder condition. DNA sequencing revealed that the proband had an
      abnormal pattern of exon 4 of the low-density lipoprotein receptor gene due to a
      heterozygosity (A/G) at nucleotide 386 and a heterozygous single-base deletion
      (A) at 685. Nucleotide 386 is the second base of codon 129, and A-->G mutation
      (D129G) changed this codon from Asp(GAC) to Gly(GGC). The single-base deletion of
      A at 685 (685del 1) is a frameshift mutation. It changes the phase of triplets,
      so that all codons are misread after this site of mutation; consequently, the
      protein expressed by the gene must be abnormal in structure and function. DNA
      analysis of the other family members showed that the 2 mutations should be
      respectively located in different alleles of the proband. Both of the 2 mutations
      have not been reported previously.

PMID- 17445539
TI  - The association of homocysteine and related factors to brachial artery diameter
      and flow-mediated dilation.
AB  - Brachial artery flow-mediated dilation (BAFMD) has been proposed as a measurement
      of the degree and severity of cardiovascular disease. The purpose of this study
      was to (1) evaluate the associations between BAFMD and homocysteine, folate,
      vitamin B(12), vitamin B(6); (2) examine the influence of 5,10
      methylenetetrahydrofolate reductase (MTHFR) genotypes on homocysteine levels and
      BAFMD; and (3) evaluate the effect of homocysteine on the baseline diameter of
      the vessel vs BAFMD. A total of 174 healthy research subjects were examined for
      BAFMD, homocysteine, folate, vitamin B(12), vitamin B(6), and MTHFR genotype,
      nucleotide 677 C-->T. The data indicated a significant inverse correlation
      between homocysteine and BAFMD (r = -0.1763, P = .02). There was a significant
      difference in BAFMD between MTHFR genotype groups (P = .01) (T/T vs C/C, P =
      .042; C/C vs C/T, P = .13; T/T vs C/T, P = .003). Homocysteine was significantly
      associated with the baseline brachial artery diameter (r = 0.1878, P = .013). The
      data confirmed a significant inverse correlation between baseline diameter and
      BAFMD (r = -0.3321, P = .0001). Regression analysis indicated that the MTHFR
      genotype, homocysteine, and age were significant predictors of BAFMD (P = .0001,
      r(2) = 0.118). When the baseline brachial diameter was incorporated into the
      model, the effect of homocysteine on BAFMD disappeared. The present data indicate
      an association between homocysteine and BAFMD and reduced BAFMD in individuals
      with the MTHFR nucleotide 677 T/T genotype, despite similar blood values for
      folate and homocysteine. Finally, the data suggest that the effect of
      homocysteine on vascular reactivity is in part a consequence of its influence on
      baseline brachial artery diameter.

PMID- 17445540
TI  - Tumor necrosis factor alpha -238G>A genotype alters postprandial plasma levels of
      free fatty acids in obese individuals with type 2 diabetes mellitus.
AB  - Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that
      impairs insulin action and alters lipid metabolism. We investigated the effects
      of genetic polymorphisms of TNF-alpha on circulating biomarkers of insulin
      resistance and lipid metabolism during an 8-hour metabolic profile test and a 2
      hour oral glucose tolerance test in subjects with type 2 diabetes mellitus.
      Subjects (N = 123) recruited were type 2 diabetic men (n = 56) and women (n = 67)
      aged 36 to 75 years with a body mass index of at least 25 kg/m(2). Blood samples
      were collected to determine postprandial changes in circulating lipid levels and
      biomarkers of insulin resistance. Subjects were genotyped by polymerase chain
      reaction-restriction fragment length polymorphism for the TNF-alpha -238G>A, 
      308G>A, and -863C>A polymorphisms. Compared with subjects who were homozygous for
      the -238G allele, carriers of the -238A allele had an altered ability to suppress
      postprandial free fatty acids as shown by an increased net incremental area under
      the curve (0.26 +/- 2.44 vs -1.33 +/- 2.71 mEq h(-1) L(-1), P = .002) during the
      8-hour metabolic profile test. This effect was observed in obese (1.04 +/- 2.42
      vs -1.68 +/- 2.70 mEq h(-1) L(-1), P = .0004) but not in non-obese (-0.63 +/-
      2.20 vs -0.95 +/- 2.71 mEq h(-1) L(-1), P = .6) individuals. Among obese
      subjects, carriers of the -308A allele had greater insulin resistance as
      estimated by the homeostasis model assessment of insulin resistance index (4.36
      +/- 2.83 vs 2.85 +/- 1.75, P = .01), but no differences were observed among non
      obese subjects (2.19 +/- 1.24 vs 1.97 +/- 0.90, P = .6). Our findings suggest
      that the -238G>A and -308G>A polymorphisms of TNF-alpha alter circulating free
      fatty acids and insulin resistance in obese subjects with type 2 diabetes
      mellitus.

PMID- 17445541
TI  - Lack of association of CPT1A polymorphisms or haplotypes on hepatic lipid content
      or insulin resistance in Japanese individuals with type 2 diabetes mellitus.
AB  - Accumulation of fat in the liver is associated with insulin resistance and type 2
      diabetes mellitus. The carnitine palmitoyltransferase (CPT) enzyme system
      facilitates the transport of long-chain fatty acids into mitochondria, and the
      gene for the hepatic isoform of CPT1 (CPT1A) is a candidate gene for metabolic
      disorders such as insulin resistance associated with fatty liver. We have now
      investigated the contribution of the CPT1A locus to hepatic lipid content (HLC),
      insulin resistance, and susceptibility to type 2 diabetes mellitus. A total of
      324 type 2 diabetic patients and 300 nondiabetic individuals were enrolled in the
      study. Eighty-seven of the type 2 diabetic patients who had not been treated with
      insulin or lipid-lowering drugs were evaluated by homeostasis model assessment
      for insulin resistance and were subjected to nuclear magnetic resonance for
      determination of HLC. A total of 19 single nucleotide polymorphisms (SNPs) were
      identified at the CPT1A locus, and linkage disequilibrium analysis revealed a
      strong linkage disequilibrium block between SNP8 (intron 5) and SNP17 (intron
      14). Neither haplotypes nor SNPs of CPT1A were found to be associated either with
      susceptibility to type 2 diabetes mellitus or with HLC or insulin resistance in
      type 2 diabetic patients.

PMID- 17445542
TI  - A common interleukin 18 haplotype is associated with higher body mass index in
      subjects with diabetes and coronary heart disease.
AB  - The pleiotropic proinflammatory cytokine, interleukin 18, plays a role in innate
      immunity and, based on mouse models, influences obesity. We investigated
      variation within the IL18 gene and its effect on markers of the metabolic
      syndrome. A tagging single nucleotide polymorphism set of 5 SNPs for the gene
      encoding interleukin 18 was selected and genotype was determined in 3 separate
      studies. In 2775 healthy middle-aged men, 6 common haplotypes were seen, but none
      was associated with body mass index (BMI). In 439 patients who underwent coronary
      artery bypass graft surgery, Hap2 (frequency, 22%) was present at a lower
      frequency than in healthy subjects and was associated with higher mean BMI
      compared with Hap1 (P = .011). In 483 men with type 2 diabetes mellitus, Hap2 was
      again associated with a higher haplotypic mean BMI (P = .002). Those homozygous
      for Hap2 had a BMI of 31.2 (1.3) kg/m(2), mean (SE), compared with 28.3 (1.0)
      kg/m(2) in those not carrying a copy of Hap2. No single SNP could fully explain
      the effects seen. Therefore, variation within IL18, previously shown to be
      associated with lower IL18 levels, is influencing measures of obesity both in men
      with type 2 diabetes mellitus and those with advanced coronary heart disease.

PMID- 17445543
TI  - Regression of acanthosis nigricans correlates with disappearance of anti-insulin
      receptor autoantibodies and achievement of euglycemia in type B insulin
      resistance syndrome.
AB  - Autoantibodies directed against specific epitopes in the insulin receptor are
      rarely the cause of either recurrent hypoglycemia or a severe form of insulin
      resistance (type B insulin resistance). Type B insulin resistance occurs more
      commonly in women of African heritage and is frequently associated with a history
      of other autoimmune diseases. We present the unusual case of a 61-year-old
      African American woman with a background of autoimmune hypothyroidism and
      autoimmune hepatitis who developed type 2 diabetes mellitus and marked facial
      acanthosis nigricans (AN) over a period of weeks. Despite treatment with multiple
      oral antidiabetic agents, she rapidly developed severe, recalcitrant
      hyperglycemia and ketoacidosis, requiring hospitalization and intravenous insulin
      administration for 4 weeks at rates of up to 180 U/h. Immunologic testing
      revealed a high titer of anti-insulin receptor autoantibodies of both
      immunoglobulin G and immunoglobulin A classes. After a recurrence of diabetic
      ketoacidosis despite aggressive management, the patient was treated with a short
      course of cyclophosphamide; within 10 weeks, she experienced striking improvement
      of her hyperglycemia as well as marked regression of the AN lesions.
      Subsequently, the patient also experienced episodes of fasting hypoglycemia,
      which resolved with a brief course of glucocorticoids. She has since remained
      euglycemic with no therapy for 5 years. We have documented, for the first time,
      regression of AN in temporal association with disappearance of circulating anti
      insulin receptor autoantibodies and achievement of euglycemia in a patient with
      type B insulin resistance.

PMID- 17445544
TI  - Depot-specific regulation of perilipin by rosiglitazone in a diabetic animal
      model.
AB  - Treatment with rosiglitazone, a potent peroxisome proliferator-activated receptor
      (PPAR) gamma agonist, results in lipid storage coupled with reduced release of
      free fatty acids into the circulation. Many studies have reported that PPAR-gamma
      agonists increase subcutaneous adiposity but have no effect on visceral fat mass.
      Perilipin, a family of phosphoproteins that coat intracellular lipid droplets in
      adipocytes, is essential for enlargement of lipid droplets. Recently, a
      functional PPAR-responsive element was identified within the murine perilipin
      gene. We hypothesized that the depot-specific regulation of perilipin by
      rosiglitazone may be associated with the fat-redistribution and insulin
      sensitizing effects of rosiglitazone. After 6 weeks of rosiglitazone treatment in
      Otusuka Long-Evans Tokushima Fatty rats, an animal model of type 2 diabetes
      mellitus, we measured changes in adiposity, triglyceride content in liver and
      muscle, morphology of the pancreas, and perilipin messenger RNA and protein
      expression in adipose tissue. Rosiglitazone increased subcutaneous adiposity,
      decreased triglyceride content of liver and muscle, decreased plasma free fatty
      acids (2107 +/- 507 micromol/L in the placebo group vs 824 +/- 148 micromol/L in
      the rosiglitazone group; P < .05), and improved insulin resistance. The islets of
      placebo-treated rats showed hypertrophy and destruction, whereas the islets of
      rosiglitazone-treated rats showed hypertrophy, but the islet architecture
      remained intact. Perilipin messenger RNA and protein expression increased in
      subcutaneous fat, but did not change in visceral fat, after rosiglitazone
      treatment. In 3T3-L1 cells, rosiglitazone pretreatment decreased lipolysis and
      increased perilipin protein. In conclusion, increased perilipin expression in
      subcutaneous fat after rosiglitazone treatment is likely to be a mediator of
      reduced lipolysis, resulting in lipid storage in subcutaneous fat, fat
      redistribution, and insulin sensitization.

PMID- 17445545
TI  - Adipokine levels and cardiovascular risk in patients with adrenal incidentaloma.
AB  - Adrenal incidentalomas (AIs) have been associated with an increased incidence of
      several cardiovascular risk factors, similar to overt Cushing syndrome. Data
      about the involvement of the adipokines in the development of insulin resistance
      and atherosclerosis in AI are completely lacking. The aim of the present study
      was to evaluate plasma interleukin 6 (IL-6), adiponectin, resistin, tumor
      necrosis factor alpha (TNF-alpha), and monocyte chemoattractant protein 1 (MCP-1)
      levels in patients with AI. Plasma IL-6, adiponectin, resistin, TNF-alpha, and
      MCP-1 levels were measured in 20 healthy subjects (6 males; 14 females; age, 58.5
      +/- 2.2 years; body mass index, 28.1 +/- 0.9 kg/m(2)) and in 20 patients (5
      males; 15 females; age, 57.9 +/- 2.0 years; body mass index, 28.0 +/- 0.8
      kg/m(2)) with AI and typical computed tomographic features of cortical adenoma,
      who were not affected by diabetes mellitus, hypertension, or other relevant
      diseases. All patients underwent anthropometric measurements and determination of
      basal corticotropin, cortisol, and urinary free cortisol excretion. Overnight
      dexamethasone test and 250-microg corticotropin test were performed in all cases.
      A subclinical Cushing syndrome was found in 3 patients, whereas the others had
      apparently nonfunctioning masses. Plasma IL-6, adiponectin, resistin, TNF-alpha,
      and MCP-1 levels were higher in patients than in controls (64.4 +/- 2.8 vs 5.5 +/
      0.6 pg/mL, 13.7 +/- 1.3 vs 3.6 +/- 0.5 microg/mL, 12.5 +/- 1.9 vs 5.1 +/- 0.2
      ng/mL, 27.0 +/- 1.5 vs 22.2 +/- 1.5 pg/mL, 172.5 +/- 20.0 vs 104.4 +/- 19.5
      pg/mL, respectively; P < .05) and apparently not affected by the presence of
      visceral obesity. Plasma IL-6 levels were negatively correlated with urinary free
      cortisol (r = -0.461, P < .05), and TNF-alpha levels were positively correlated
      with cortisol after the administration of 1 mg dexamethasone (r = 0.636, P <
      .01). In conclusion, patients with AI may show increased levels of adipokines
      (apparently not related to the presence of diabetes, hypertension, or obesity),
      which may be affected by the presence of the adrenal adenoma. For some
      adipokines, a direct production from the adrenal gland may be hypothesized even
      if other studies are needed to better investigate the role of adipokines in
      states of altered cortisol secretion.

PMID- 17445546
TI  - Serum resistin level is associated with insulin sensitivity in Japanese patients
      with type 2 diabetes mellitus.
AB  - Impaired insulin secretion and decreased insulin sensitivity are the main
      pathophysiologic features responsible for development of hyperglycemia in type 2
      diabetes mellitus. Insulin resistance is often associated with increased adipose
      tissue mass. To examine which variables influence insulin sensitivity, we
      compared metabolic parameters, serum resistin, leptin, and adiponectin
      concentrations to the insulin sensitivity, obtained by frequently sampled
      intravenous glucose tolerance test using the minimal model analysis, in 113
      Japanese patients with type 2 diabetes mellitus. Duration of diabetes, fasting
      plasma glucose, fasting insulin, homeostasis model assessment of insulin
      resistance index, and serum resistin concentration were significantly higher in
      the insulin-resistant subgroup compared with the insulin-sensitive subgroup and
      correlated with insulin sensitivity. Stepwise regression analysis also identified
      these parameters as independent regulators of insulin sensitivity. The present
      study reconfirmed that fasting insulin level or homeostasis model assessment of
      insulin resistance would be a surrogate measure of insulin resistance and
      demonstrated that insulin resistance increases progressively after the onset of
      overt diabetes and that the serum resistin level is associated with insulin
      sensitivity, suggesting that resistin plays an important role in the development
      of insulin resistance in Japanese patients with type 2 diabetes mellitus.

PMID- 17445547
TI  - Serum osteoprotegerin and soluble receptor activator of nuclear factor kappaB
      ligand levels in patients with a history of differentiated thyroid carcinoma: a
      case-controlled cohort study.
AB  - Overt hyperthyroidism is associated with changes in bone metabolism, whereas the
      effect of levothyroxine (L-T4) load in patients with differentiated thyroid
      carcinoma (DTC) is controversial. The aim of our study was to evaluate
      osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappaB
      ligand (RANK-L) in patients with DTC with suppressed endogenous thyrotropin due
      to L-T4 regimen. A cohort of 80 subjects with DTC (68 women and 12 men; age
      range, 27-81 years) was studied. A cohort of 55 subjects with a history of
      partial or total surgery for nonmalignant thyroid pathology served as a control
      group. Groups were matched for sex, age, and body mass index. Per-week dosage of
      L-T4 was significantly higher in patients with DTC than in controls (P < .001).
      More elevated free T(4) concentrations (P < .001) and more suppressed thyrotropin
      and thyroglobulin levels (P < .001) were found in subjects with DTC than in
      controls. No difference in serum or urinary parameters related to bone metabolism
      or dual-energy x-ray absorptiometry was noted between the groups. Overall, OPG
      levels were similar in both groups but were significantly (P = .03) lower in
      postmenopausal women with DTC than in postmenopausal control women. Only control
      women showed lower OPG levels in premenopausal than in postmenopausal (P = .002)
      conditions. Overall, RANK-L levels were significantly higher (P = .03) in
      subjects with DTC than in controls. In both groups, OPG and RANK-L levels were
      unrelated to each other. A significant positive correlation was seen between OPG
      levels and age in both subjects with DTC (P < .001) and controls (P < .001).
      Serum RANK-L correlated negatively with age in subjects with DTC (P = .05).
      Although there were several differences in L-T4 dosages, OPG and RANK-L levels
      were similar in patients with a history of DTC and those with a history of
      nonmalignant thyroid diseases. The correlation between circulating OPG and RANK-L
      levels was not significant. The increase in OPG with age indicates its protective
      role in bone loss. The cause of bone loss after long-term L-T4 load will be more
      extensively studied.

PMID- 17445548
TI  - 13C enrichment of carbons 2 and 8 of purine by folate-dependent reactions after
      [13C]formate and [2-13C]glycine dosing in adult humans.
AB  - The 10-formyl moiety of 10-formyltetrahydrofolate is the source of carbons at the
      positions 8 (C(8)) and 2 (C(2)) of the purine ring, originating from formate and
      a few amino acids. Uric acid is the final catabolic product of purines. In adult
      humans, we independently measured the (13)C enrichment of the C(2) and C(8)
      positions of urinary uric acid after an oral dose of [(13)C]sodium formate and
      that of the C(2) and C(8) plus C(5) positions after [2-(13)C]glycine. A liquid
      chromatography-mass spectrometric method was used to measure the (13)C enrichment
      of uric acid in urine, which was collected for 3 to 4 days. Purine catabolism to
      uric acid does not alter the positions of carbons in the ring. After the formate
      dose, the (13)C enrichment at C(2) was greater than at C(8), and a circadian
      rhythm was observed in the enrichment at C(2). After the glycine dose, the C(8)
      plus C(5) positions were enriched, whereas no significant enrichment at C(2) was
      found. These (13)C enrichment patterns are not consistent with previous accepted
      metabolism. To our knowledge, this is the first study to investigate (13)C
      enrichment from formate and glycine independently into the C(2) and C(8)
      positions of purine in the same subjects. Possible mechanisms explaining our
      findings are discussed. Oral [(13)C]formate or [2-(13)C]glycine dosing and urine
      collection can be used to study purine biosynthesis in humans.

PMID- 17445549
TI  - The adipose cell lineage is not intrinsically insulin resistant in polycystic
      ovary syndrome.
AB  - Selective resistance to the effects of insulin on glucose metabolism in skeletal
      muscle and adipose tissue is a key feature of polycystic ovary syndrome (PCOS).
      The pathogenesis of insulin resistance in skeletal muscle in PCOS involves
      interaction of in vivo environmental factors with intrinsic defects in insulin
      signaling. We aimed to determine whether (1) intrinsic defects in insulin
      action/signaling and cytokine secretion were present in adipose cells in PCOS and
      (2) insulin resistance can be induced in control adipose cells by culture in
      medium conditioned by insulin-resistant PCOS fibroblasts. Subcutaneous abdominal
      preadipocytes from obese women with PCOS (n = 7) and age- and body mass index
      matched controls (n = 5) were cultured for several generations in vitro. Basal
      and insulin-stimulated glycogen synthesis and basal glucose transport did not
      differ in the preadipocytes from women with PCOS and controls. Abundance of
      insulin receptor (IR) beta subunit, insulin receptor substrate (IRS) 1 and 2, p85
      subunit of phosphatidylinositol 3-kinase, and extracellular signal-regulated
      kinase (ERK)1/2 activation did not differ. Secretion of tumor necrosis factor
      alpha and interleukin 6 did not differ. Insulin action on glycogen synthesis in
      control preadipocytes was not altered by coculture with or growth in media
      conditioned by PCOS skin fibroblasts with constitutive serine phosphorylation of
      IRbeta subunit (IR ser+), indicating that IR ser+ cells do not secrete an insulin
      resistance-inducing factor. We conclude that in contrast to skeletal muscle and
      skin fibroblasts, there is no evidence for intrinsic defects in insulin signaling
      in the PCOS adipose cell lineage, indicating that insulin resistance in these
      cells is likely due to factors in the in vivo environment.

PMID- 17445551
TI  - Conversion from a calcineurin inhibitor-based immunosuppressive regimen to
      everolimus in renal transplant recipients: effect on renal function and
      proteinuria.
AB  - New immunosuppressive agents are being actively researched to avoid complications
      of chronic allograft nephropathy (CAN), calcineurin inhibitor (CNI)
      nephrotoxicity, and posttransplantation cancer. The family of mTOR inhibitors
      offers a unique immunosuppressive opportunity to avoid CNI toxicity and reduce
      the incidence of malignancy. Nevertheless, increasing data have demonstrated that
      sirolimus (SRL), the first mTOR introduced in the treatment of solid organ
      transplant recipients, induces proteinuria, an adverse event that could produce
      deterioration of long-term renal function. In this short-term study of patients
      followed for 1 to 16 months, we examined changes in renal function and
      proteinuria among renal transplant recipients converted from a CNI-based regimen
      to an everolimus (EVL)-based one, a recently introduced mTOR inhibitor. Our data
      showed that renal function can be optimized after conversion to EVL by up to 42%
      in recipients showing CAN grade 1 or 2, or CNI nephrotoxicity. Importantly,
      patients who improved their creatinine clearance did not show increased
      proteinuria measured in a voided specimen as the ratio of urinary protein and
      creatinine concentration (P/C). These results, if confirmed with long-term follow
      up and a larger number of patients, would allow us to consider EVL as a promising
      agent for maintenance immunosuppressive regimens in kidney transplantation.

PMID- 17445552
TI  - Case report of a kidney transplant recipient converted to everolimus due to
      malignancy: resolution of bronchiolitis obliterans organizing pneumonia without
      everolimus discontinuation.
AB  - The use of proliferative signal inhibitors (PSIs) in immunosuppression-related
      malignancies opens new roads for increasing the survival and quality of life in
      patients with solid organ transplantation. A 56-year-old female recipient of a
      living donor renal allograft (1990), who was immunosuppressed with cyclosporine
      (CsA; Neoral), azathioprine, and steroids, did initially well with acceptable
      renal function. During the last 5 years she required local therapy due to
      posterior vaginal lip human papillomavirus (HPV) lesions. In 2000, she
      discontinued azathioprine and the CsA doses were reduced to 100 mg daily. The
      local lesion showed a good response to reduced immunosuppression. In February
      2005, the lesion reappeared and a biopsy showed malignancy. Local surgery was
      performed and CsA was replaced by everolimus (EVL; Certican). Two months after
      treatment initiation, the patient developed cough, dyspnea, and low-grade fever.
      Chest X-ray showed a lesion at the base of the left lung compatible with
      pneumonitis. After fiberbronchoscopy a diagnosis of bronchiolitis obliterans
      organizing pneumonia (BOOP) was obtained. She was treated with increased doses of
      oral steroids. EVL was never discontinued. The radiological lesion disappeared
      and the malignancy is currently in remission. In summary, a case of gynecological
      cancer in a renal transplant recipient was treated by surgical removal. After 1
      year of immunosuppression with EVL, no recurrence has been observed. The adverse
      event (BOOP) was probably related to the PSI treatment and was controlled with an
      increased dose of steroids without discontinuing EVL.

PMID- 17445553
TI  - Therapeutic drug monitoring of mycophenolic acid in kidney transplant patients: a
      abbreviated sampling strategy.
AB  - Mycophenolic acid (MPA) levels have demonstrated a good correlation with clinical
      outcomes, but with great pharmacokinetic variability between patients.
      Therapeutic drug monitoring (TDM) is recommended to include a 12-hour area under
      the concentration-time curve (AUC). Since full AUC estimates are not practical
      for routine monitoring, limited sampling strategies have been suggested. We
      evaluated MPA pharmacokinetics in 18 stable renal transplant patients receiving
      mycophenolate mofetil (MMF) as part of their immunosuppressive therapy. The
      correlation between measured and estimated AUC was assessed using 4 different
      sparse sampling algorithms. The mean values for C(0) and AUC(0-6h) were 1.8 +/-
      1.2 mg/L and 31.1 +/- 14.8 mg*h/L, respectively. The dose-corrected AUC(0-6h) was
      35.4 +/- 17.9 mg*h/L. Regarding the single time points, C(0) showed a low
      correlation with AUC(0-6h) (r(2) = .34); C(1.5), the best correlation (r(2) =
      .72); and C(3), the worst (r(2) = .07). Sparse sample algorithms used to estimate
      12-hour AUC including C(0), C(1), C(2), C(3), C(4), and/or C(6) showed a good
      correlation with the calculated AUC(0-6) (r(2) = .81-.96). The algorithm that
      used C(0), C(1), C(2), and C(4) showed the best correlation, but we also found a
      good correlation (r(2) = .91) with C(0), C(1), and C(2). Based on these results,
      we have suggested using the 3-point algorithm (C(0), C(1), and C(2)) for MPA TDM
      in stable renal transplant patients due to the good correlation with drug
      exposure and better functionality than an algorithm using a 4-hour postdose
      measurement.

PMID- 17445554
TI  - Report of the experience with enteric-coated sodium mycophenolate in a de novo
      population of kidney transplant recipients at high risk for delayed graft
      function.
AB  - The introduction of mycophenolate as an adjuvant in immunosuppressive regimes has
      improved clinical outcomes of transplant patients due to a reduced incidence of
      acute rejection episodes. Nevertheless, the need for dose adjustments or therapy
      discontinuations (up to 45% in some series), have downgraded the efficacy of
      mycophenolate mofetil (MMF). From October 2003 to April 2005, 36 kidney
      transplantations were performed at our site. The immunosuppressive protocol
      included induction with basiliximab, administered on days 0 and 4
      posttransplantation, cyclosporine microemulsion (CsA-ME) monitored by
      concentrations at 2 hours (C2), enteric-coated sodium mycophenolate (EC-MPS; 720
      +/- 180 mg bid), and steroids. Mean follow-up time was 7.3 +/- 4.4 months.
      Fourteen patients (38.9%) experienced delayed graft function (DGF). Seven (19%)
      episodes of acute rejection included 5 graded as I-A, 1 as grade I-B, and 1 as
      grade II-A. There were discontinuations of EC-MPS. Regarding gastrointestinal
      (GI) adverse events, there were 2 episodes of noninfectious diarrhea, 1
      gastritis, and 1 upper GI hemorrhage. There were 11 infections: 4 in the urinary
      tract; 3 in the lung; 3 in the GI tract; and 1 CMV infection. There were no
      discontinuations of EC-MPS reported [corrected] Two (6%) graft losses were
      reported to be due to sepsis. In this group of patients who experienced a high
      incidence of DGF, the combination of basiliximab, CsA-ME (monitored by C2), and
      EC-MPS resulted in low Banff grade acute rejection episodes which were all
      responsive to steroids. The incidence of GI adverse events was only 11%.

PMID- 17445555
TI  - Converting to a generic formulation of mycophenolate mofetil in stable kidney
      transplant recipients: 1 year of drug surveillance and outcome.
AB  - OBJECTIVE: The objective of this study was to compare the pharmacokinetic
      profiles of a generic formulation with the innovator mycophenolate mofetil (MMF).
      METHODS AND PATIENTS: Thirteen patients with stable renal grafts received MMF
      posttransplantation (mean, 32 months; confidence interval 95%: 51, 9-12, 36).
      Graft function improved significantly (serum creatinine levels 2.72 +/- 1.75
      mg/dL to 1.9 +/- 0.66 and 1.79 +/- 0.86 mg/dL at 12 and 30 months, respectively;
      P < .05). Three point (basal, 2, and 6 hours) profiles were performed. Five
      patients were switched 1:1 to a generic formulation for 60 days and repeating the
      pharmacokinetics were repeated. Afterwards, they returned to the innovator MMF
      for 45 days. Finally, all patients received generic MMF, repeating the
      pharmacokinetics between 15 days and 6 months later. RESULTS: The area under the
      curve (AUC 0-6) of MPA was 52.68 +/- 17.5 microg/mL*hr, with 61.5% of basal
      determinations (Co) under 5 microg/mL (4.08 +/- 0.74). The Pearson correlation
      coefficient was high between both MMF formulations regarding FMPA AUC 0.768 (P <
      .005), Co (0.774; P < 0.05), and C6 (0.996; P < .005). GMPA AUC were similar
      (Pearson) 0.7 (P < .01), Co 0.99 (P < .01), and C6 0.86 (P < .01). C2 MMF levels
      were variable and showed poor correlation. FMPA AUC of generic and original
      formulations after 60 days had tight correlation. (Pearson 0.883; P < .025) and
      comparing 15 and 60 days postconversion with generic drug in the same patients
      were similar (Pearson 0.58; P < .025). Renal function at 12 months remained
      stable postconversion. CONCLUSIONS: Conversion to generic MMF in stable renal
      transplant recipients showed good clinical results.

PMID- 17445556
TI  - Pediatric liver retransplantation: indications and outcome.
AB  - INTRODUCTION: Liver transplantation is the only treatment for end-stage liver
      disease. Not all patients have a favorable outcome. Graft failure secondary to
      primary nonfunction, vascular complications, or chronic rejection among other
      problems may lead to retransplantation. Retransplantation represents 8% to 29% of
      liver transplantations in the pediatric population. The aim of this study was to
      present our experience with retransplanted children by analyzing the indications
      and the results. METHODS: All patients were prospectively included in our
      database, including 125 children. We included the indications for
      retransplantation, complications, and mortality. Kaplan-Meier curves were used
      for survival analysis. RESULTS: Since 1994, 125 patients were transplanted and 25
      were retransplanted (20%), including 5 who received a third graft. Primary
      nonfunction represented 30% of the indications for retransplantation and hepatic
      artery thrombosis, 20%. Six of 25 patients who received a first retransplantation
      and 2 of 5 who received a second retransplantation died. The most frequent cause
      of death was multiorgans failure. The survivals at 1 and 5 years were 82% and 76%
      for children receiving a first retransplantation, and 60% at 1 and 5 years for
      those who received a second retransplantation. CONCLUSIONS: Organ failure after
      liver transplantation was a common event in pediatric transplantation. Survival
      was similar between patients transplanted once and those who received one
      retransplantation. Survival decreased among patients who received a third graft
      but was maintained at 60%, which is better than most published results for first
      retransplanted patients. Retransplantation is a valid option with good results
      for selected pediatric cases.

PMID- 17445557
TI  - Oral ulcers produced by mycophenolate mofetil in two liver transplant patients.
AB  - Oral ulcers are a frequent problem in transplant medicine. It is important to
      consider infectious etiologies, exacerbated by the immunosuppressive treatment,
      but other etiologies are also possible, like adverse drug reactions.
      Mycophenolate mofetil (MMF) is an immunosuppressive medication that has been used
      in combination with calcineurin inhibitors and steroids. Reports of renal
      transplant patients with oral ulcers related to MMF have appeared lately and
      herein we have described 2 cases in liver transplant patients. Their oral ulcers
      resolved quickly after suspension of the medication. Our 2 cases in liver
      transplant patients represented a unique setting for this type of complication.

PMID- 17445558
TI  - Family interactions of liver transplanted children: are they normal?
AB  - Several psychosocial and behavioral problems have been reported in liver
      transplanted children. Most publications have focused on them, without
      considering their family environment. The aim of this study was to evaluate the
      interaction between liver transplanted children and their families, compared with
      a healthy control group. We selected liver transplanted children, between 8 and
      12 years of age, with at least 6 months follow-up posttransplantation and in good
      clinical condition. Family structure also included 1 to 3 other children.
      Evaluable patients must have been living with their parents throughout the whole
      posttransplantation period. They were compared with a similar group of children
      without any chronic disease. A written informed consent was signed by both
      parents. All families were evaluated using a standard test consisting of
      different situations. The information was evaluated by 3 independent experts.
      Factors evaluated were limits (rules and limits of behavior), alliance-opposition
      (interaction between members to act), and hierarchy. Scoring was given to all
      observed acts. Statistical analysis was performed using chi-square tests with P <
      .05 considered significant. No statistical differences were found between groups
      in limits, alliance, and hierarchy. Our results showed that there were no
      differences in family structure and behavior between families of liver
      transplanted and healthy children belonging to a similar socioeconomic level.

PMID- 17445559
TI  - Heart transplantation in chile: preliminary report from the Gustavo Fricke
      hospital in Vina del Mar.
AB  - OBJECTIVE: The aim of this study was to analyze our results as the national
      reference center of the public health network in Chile. PATIENTS AND METHODS:
      Retrospective analysis of all transplantations performed between 1998 and 2005
      was done and actuarial survival estimates were calculated according to Kaplan
      Meier. RESULTS: Heart transplantations were performed in 25 patients of mean age
      43 +/- 11.2 years. Eight patients (32%) were transplanted from a national
      priority list; all patients were under intensive care support with inotropic
      therapy, 4 were mechanically ventilated, and 1 required an intra-aortic counter
      pulsation balloon. The average time on the waiting list was 145 days in nonurgent
      cases and 9.4 days in urgent ones. Perioperative mortality occurred in 1 patient
      (4%) due to primary graft failure; 2 patients died due to infectious
      complications during the first year of follow-up; and 1 died due to a non
      cytomegalovirus (CMV) infection at 51 months after transplantation. Two patients
      developed acute rejection with full recovery. The most common morbidities in the
      current series were hypertension (71%); hyperlipidemia (71%); renal dysfunction
      (24%); diabetes (10%); and vasculopathy (10%). Actuarial survival rates were
      87.2% and 74.7% at 12 and 86 months, respectively. At 7 years follow-up, 20
      patients were in New York Heart Association (NYHA) Class I and one Class II.
      CONCLUSION: Our heart transplantation program showed comparable results in the
      short and midterm follow-up when compared with other international reports,
      confirming that heart transplantation is an excellent therapeutic option for
      patients with end-stage heart failure.

PMID- 17445560
TI  - Cytomegalovirus infections in cardiac transplant patients: an experience at a
      clinical hospital, university of Chile.
AB  - BACKGROUND: Since cytomegalovirus (CMV) infects between 20% and 50% of heart
      transplant patients, we reviewed our experience in 7 cases of this infection.
      METHODS: A prospective analysis of CMV infection was performed in heart
      transplant patients who received cyclosporine, azathioprine, or mycophenolate
      mofetil, and prednisone. An elevated creatinine de novo was managed with antibody
      induction. RESULTS: Between August 2001 and December 2005, we performed 22 heart
      transplants and 1 heart plus kidney transplant. Twenty-two patients were positive
      for CMV before transplantation. One patient died early because of graft failure.
      Immunosuppression included cyclosporine and prednisone (100%), azathioprine
      (52%), or mycophenolate (47%). Two recipients were induced with thymoglobulin and
      13 with Daclizumab, while 8 did not receive any antibody. Nineteen patients
      received prophylaxis for CMV. Seven patients (30%) showed CMV infection, 6 of
      whom had received prophylaxis. Symptoms started at an average of 107 days
      posttransplantation in patients with prophylaxis. Three patients had gastritis, 2
      pneumonia, and 1 colitis. One patient had concomitant lung aspergillosis. The two
      patients who received ATG developed CMV infections; 3 of the 12 with Daclizumab;
      and 2 who did not receive antibody. Of the CMV-infected subjects, 5 were on
      azathioprine and 2 on mycophenolate. All patients were treated with gancyclovir.
      The 1 patient with concomitant aspergillosis died. CONCLUSIONS: The incidence of
      infection by CMV was 30%. Prophylaxis seemed to delay infection. Daclizumab
      induction did not increase the risk for CMV.

PMID- 17445561
TI  - First case of simultaneous heart plus kidney transplantation in Chile: case
      report.
AB  - Advanced renal disease is a formal contraindication to heart transplantation, and
      heart failure may make a patient ineligible for kidney transplantation. The
      International Society of Heart and Lung Transplantation has reported 336
      simultaneous heart and kidney transplantations with a 70% rate of 5 year
      survival. Herein we have presented the first case of simultaneous heart plus
      kidney transplantation in Chile. The patient is a 62-year-old man with diabetes
      mellitus and arterial hypertension who in 1997 had a myocardial infarction with
      cardiogenic shock and acute renal failure. He underwent a coronary bypass but
      developed progressive heart failure, with an ejection fraction less than 20% and
      moderate mitral regurgitation. He required chronic hemodialysis and survived a
      cardiac arrest, receiving an implantable cardioverter defibrillator.
      Transplantation was performed in 2004 in 2 phases: initially a heart, followed by
      a kidney transplantation. Immunosuppression included Daclizumab, cyclosporine,
      mycophenolate mofetil (MMF) and steroids. He developed acute renal failure but
      did not receive dialysis. He left the hospital at 25 days posttransplantation.
      Two years following double transplantation, he has not shown acute rejection
      episodes of either the cardiac or the kidney graft. Both cardiac and renal
      functions are normal. In conclusion, simultaneous heart plus kidney
      transplantations offer a good alternative treatment for patients with advanced
      disease of both organs.

PMID- 17445562
TI  - Search for unrelated donor umbilical cord blood units for allogeneic stem cell
      transplantation: results in two time periods.
AB  - Umbilical cord blood (UCB) banks have increased their stock worldwide in the past
      years. There are more than 230,000 available units today. The ideal UCB graft is
      a unit that is matched in five or six of six HLA. A, B (low-resolution) and DRB1
      (high-resolution) alleles and which has over 2.5 x 107 nucleated cells/kg body
      weight (BW). Four of six matched units are also used specially if the cell dose
      gives more than 3 x 10(7) nucleated cells/kg BW. Our unrelated donor UCB
      transplant program was started in 1996 searching international cord blood banks
      (Netcord, New York) for patients with a definitive or potential indication for
      stem cell transplantation who lacked a matched family donor. PATIENTS AND
      METHODS: From 1995 to 1996, a search was initiated for 87 patients with malignant
      (n = 56, 37 acute leukemia) and nonmalignant conditions (16 congenital diseases,
      14 aplastic anemia). Patient data along with low-resolution A, B, and DR typing
      were sent to the New York Blood Center, along with a blood sample for high
      resolution DRB1 typing. Parallel searches were done in the Netcord database among
      UCB units with reported high-resolution DRB1 typing. Forty-eight searches were
      done between 1995 and 2000 (31 with high resolution) and 39 were done between
      2000 and 2005 (33 with high resolution). UCB units were considered adequate if
      they had more than 2.7 x 10(7) cells/kg BW. RESULTS: During the first period,
      four patients (13%) matched five of six high-resolution unit and 21 (67%) a four
      of six match. During the second period, 15 patients (46%) found a five of six
      match and 16 (48%) a four of six match (P = .012). CONCLUSION: Nearly half of our
      patients find an optimal matched UCB unit for transplantation in international
      banks. The creation of a local UCB bank in our country is supported by these
      data.

PMID- 17445563
TI  - Generation of dendritic cells with regulatory properties.
AB  - Dendritic cells (DCs) are professional antigen presenting cells with the ability
      to induce and regulate an immune response. DCs that capture and present antigen
      under noninflammatory conditions maintain an immature phenotype and acquire
      tolerogenic properties. These DCs generate regulatory T lymphocytes that
      potentiate tolerogenic responses. Here we developed a method for the generation
      of immature murine DCs able to process and present a specific antigen in a
      tolerogenic context. Immature DCs were prepared from bone marrow precursors after
      differentiation with granulocyte-macrophage colony-stimulating factor (GM-CSF) in
      the presence of vitamin D(3) and characterized by their low expression of major
      histocompatibility complex class (MHC) II and CD86 molecules. Purified phagosomes
      containing either MHC II molecules or ovalbumin were used to deliver antigens to
      immature DCs. More than 80% of the DCs captured the phagosomes, while maintaining
      a low expression of maturation markers and showing basal levels of secretion of
      activating cytokines such as interleukin (IL)-2 and IL-12. Treatment of the
      immature DCs with lipopolysaccharides (LPS) increased IL-10 secretion, in
      agreement with their anti-inflammatory and immune regulatory properties.
      Cocultures of transgenic OT-II T lymphocytes with the immature DCs carrying OVA
      phagosomes succeeded in generating a subpopulation of regulatory T lymphocytes
      characterized by the expression of CD4, CD25, CD62L, and Foxp3. Taken together,
      our results suggest that vitamin D(3) generates immune tolerance through the
      modulation of DC phenotype and could be useful to induce tolerance to
      allotransplants.

PMID- 17445565
TI  - Immunobiology of rejection and adaptation.
AB  - Transplantation is an acceptable therapy for failing organs, however, the balance
      between prevention of acute rejection and immunosuppressant-induced toxicity
      remains elusive. Organ transplantation from a genetically disparate donor induces
      an immune response toward donor antigens in the recipient. An uncontrolled
      cumulative effect of these responses may jeopardize the recipient's life and
      destroy the grafted tissue. The donor antigen in the form of passenger leukocytes
      from the allograft migrating to the organized lymphoid collection is a
      prerequisite for initiation of acute rejection. In the host lymphoid tissue donor
      specific dendritic cells primed with donor peptide activate naive CD4 helper T
      cells which in turn activate effector CD8 T-cell clones through the release of
      cytokines. Activated effector CD8 cells return to the graft and augment
      destructive activity with the help of adhesive molecules and perforin. This seems
      to be the mechanism of adaptive immunity to destroy viral pathogens; the pattern
      of allograft injury is not much different. Adaptation and tolerance are based on
      the principle of exhaustion of donor-specific immune responses by an activation
      deletion-exhaustion pathway.

PMID- 17445566
TI  - In pursuit of the ultimate: the initial Ahmedabad journey toward transplantation
      tolerance.
AB  - We designed a prospective clinical trial of 357 patients divided in two groups-
      treated (n = 201) and controls (n = 156)--to evaluate effects of donor
      hematopoietic stem cell transplantation (HSCT) with minimal nonmyeloablative
      conditioning for tolerance induction in living related donor renal allograft
      recipients. Conditioning included donor leukocyte infusions, target-specific
      irradiation, anti-T-cell antibody, cyclophosphamide, cyclosporine (CsA), followed
      by bone marrow (BM)-derived and peripheral blood stem cell (PBSC) infusion into
      thymus, liver, BM, and periphery, with mean total dose of 20 x 10(8) nucleated
      cells/kg body weight (BW) (mean CD34(+) count: 0.9%) pretransplantation. CsA (3
      mg/kg BW/d) and prednisolone (10 mg/d) were used for immunosuppression.
      Azathioprine/mycophenolate mofetil were added in the event of an acute rejection
      episode. The controls underwent transplantation with three drug
      immunosuppression. With a mean follow-up of 21.5 months, the treated cohort
      showed better allograft function with mean serum creatinine (SCr), 1.42 +/- 0.31
      mg% in contrast with the controls mean SCr, 1.61 +/- 0.52 mg% (P < .0001) at 23.9
      months follow-up. One-year allograft/patient survival was 95%/96.7% versus
      89%/93.4%, respectively. Peripheral blood chimerism by fluorescent in situ
      hybridization was 0.8% +/- 0.2% in the subset of treated patients with gender
      mismatched donors. No graft-versus-host disease was noted. Nine patients with
      donor-specific cytotoxic alloantibodies pretransplantation showed a decrease in
      positivity to <15% post-HSCT and were transplanted safely. A transient rise in
      donor-specific cytotoxic alloantibodies was noted in 19 treated patients post
      HSCT, 14 of whom returned to the transplantable range within 2 weeks and five
      required a desensitization protocol. "Prope" tolerance may be induced in living
      related donor renal transplantation across major histocompatability complex
      barriers using HSCT with minimal nonmyeloablative conditioning.

PMID- 17445567
TI  - Successful generation of donor specific hematopoietic stem cell lines from co
      cultured bone marrow with human embryonic stem cell line: a new methodology.
AB  - We report the generation of 30 healthy human embryonic stem cell (h-ESC) lines
      from 33 voluntary oocyte donors using a donor somatic cell nuclear transfer
      (SCNT) technique on 190 oocytes. Our aim was to coculture them with their own
      bone marrow (BM) to generate hematopoietic progenitor cells for therapeutic
      purposes. Pluripotency and undifferentiated stage were confirmed using molecular
      cell surface markers. Normal karyotype of these cell lines was confirmed. Here we
      demonstrate that SCNT-h-ESCs differentiate to hematopoietic precursors when
      cocultured with unmodified, nonirradiated donor BM. We did not use any xenogeneic
      material for this hematopoietic differentiation. Hematopoietic precursors derived
      from them expressed cell surface antigens CD45/34. When further cultured with
      hematopoietic growth factors these hematopoietic precursors formed characteristic
      myeloid, erythroid, and megakaryocyte lineages. Phenotypic CD34+ cells derived
      from NT-h-ESCs were functionally similar to their counterparts in primary
      hematopoietic tissues like BM, umbilical cord, and blood. More terminally
      differentiated hematopoietic cells derived from h-ESCs under these culture
      conditions also expressed normal surface antigens like glycophorin A on erythroid
      cells, CD15 on myeloid cells, and CD41 on megakaryocytes. We report generation of
      hematopoietic progenitor cells from h-ESC lines by a SCNT technique, with
      differentiation into further lineages with structural and functional similarities
      to their adult counterparts in vivo. This novel alternative source of CD34+ stem
      cells from h-ESC lines generated without any xenogeneic material might be used to
      create transplantation tolerance, to implement regenerative medicine, and to
      treat autoimmune disorders.

PMID- 17445568
TI  - Transplant rejection under the microscope.
AB  - Using standard stains for light microscopy, selected stains for
      immunofluorescence, and occasionally electron microscopy, a renal biopsy can be
      extremely valuable when managing a renal allograft recipient. Frequently, the
      results of the biopsy change the initial clinical impression and the therapy for
      the patient. The hallmarks of acute cellular rejection are an interstitial
      mononuclear infiltrate and significant tubulitis. Occasionally, in severe
      cellular rejection there may be mononuclear infiltration of the endothelium of
      the arteries. Humoral rejection morphologically is characterized by significant
      endothelial damage both in the arteries and the glomeruli. This endothelial
      damage can result in actual thrombus formation. The presence of C4d in
      peritubular capillaries is a definite indication of humoral rejection. Chronic
      rejection results from more prolonged slow damage to the endothelial cells of the
      vessels, resulting in progressive obliteration of their lumens. This change
      results in downstream ischemia, leading to tubular loss and interstitial
      fibrosis. Cyclosporine toxicity and BK polyoma virus involvement of the kidney
      can mimic rejection clinically and sometimes morphologically.

PMID- 17445569
TI  - Innate immunity-mediated allograft rejection and strategies to prevent it.
AB  - Experimental and clinical evidence has accumulated in support of the notion that
      oxidative injuries to allografts induce an adaptive alloimmune response which
      leads to acute rejection. The link between the initial injury and subsequent
      rejection is the innate immune system represented by injury-activated donor
      derived and recipient-derived dendritic cells which interact with naive T cells
      of the recipient to induce an alloimmune T-cell response. Therefore, time is
      mature to consider potential therapeutic strategies that are able to suppress
      events of innate immunity. Such strategies refer to a "time-restricted
      therapeutic window" that includes treatment of the donor during organ removal and
      the recipient during allograft reperfusion. Major targets of such treatment
      include (1) mitigation of the oxidative allograft injury; (2) inhibition of
      injury-induced activation of complement; (3) inhibition of Toll-like receptor
      (TLR)-mediated and innate lymphocyte-triggered maturation of dendritic cells; and
      (4) blockade of innate effector functions. A considerable variety of promising
      experimental studies about the prevention/inhibition of innate immune events has
      already been performed, including the successful experimental use of gene
      silencing methods, eg, using RNA interference technology with the application of
      small interfering RNA (siRNA). In addition, a few clinical trials with
      antioxidants (edaravone, SOD-mimetics), complement inhibitors (pexelizumab, TP
      10) in patients with acute myocardial infarction, and TLR4 antagonists (TAK-242,
      E-5564) in patients with sepsis have been performed or are underway. Performance
      of similar clinical trials in transplant patients with antioxidative drugs,
      complement inhibitors, and/or TLR4 antagonists is urgently warranted; siRNAs
      appear to be extremely attractive for investigation in experimental allogeneic
      transplant models.

PMID- 17445570
TI  - Histocompatibility testing for highly sensitized transplant candidates.
AB  - HLA antibodies can develop for many different reasons and are often present in
      the serum of patients awaiting renal transplantation. These antibodies can limit
      the patient's ability to find a compatible donor and are a risk factor for poor
      graft outcome. Detection of HLA antibodies is important for identifying
      compatible donors, assessing the pretransplantation risk for rejection, and
      diagnosing humoral rejection posttransplantation. The results of antibody screens
      are also useful when interpreting crossmatch results. Assays used for detecting
      panel-reactive and donor-specific HLA antibodies, including cytotoxicity, flow
      cytometry, and solid phase assays, are described in this review.

PMID- 17445571
TI  - Mixed chimerism approach to induction of transplant tolerance: a review of the
      Massachusetts General Hospital experience.

PMID- 17445572
TI  - Deletion of donor-reactive cells as a new conditioning regimen for allogeneic
      bone marrow transplantation.
AB  - Progress in the development of less toxic conditioning for bone marrow
      transplantation (BMT) came with the understanding that acceptance of mismatched
      BM does not require myeloablation of recipients. Lymphocyte deletion by a
      cocktail of immunosuppressive drugs is generally sufficient to ensure engraftment
      of compatible BM cells. However, reduced intensity conditioning (RIC) protocols
      available today do not provide robust tolerance to mismatched allogeneic BM.
      Herein we discuss 2 new experimental approaches to RIC protocols with the aim of
      facilitating allogeneic BM engraftment. Both conditioning regimens are based on
      selective deletion/inactivation of donor-reactive cells before BMT. Our data show
      that the first conditioning protocol, comprising priming of recipients by a donor
      specific lymphocyte transfusion (DST) on day -2 and a single injection of
      cyclophosphamide, a drug that is predominantly toxic for proliferating cells, on
      day -1, consistently improves engraftment of allogeneic BM (day 0) in all
      experimental models tested. The second engraftment enhancing approach is based on
      the blockade by antagonistic reagents of the signaling pathways that govern the
      antigen-induced immune response. Combining the signaling blockade with the
      deletion of activated donor-reactive cells by cytoreductive agents provides
      additional benefits for transplantation across major histocompatibility barriers.

PMID- 17445573
TI  - Prospects in xenotransplantation: a personal view.
AB  - There are 3 major obstacles to performing transplantations from pig to human.
      They are as follows: a powerful immune barrier, a potential risk for transmitting
      microorganisms, particularly endogenous retrovirus from animal-to-human, and
      ethical issues related to patients and society at large. However, steady progress
      is currently being made in overcoming these obstacles. Once pig organs can be
      transplanted into humans, there will be unlimited access to undamaged organs and
      cells for transplantation, and surgeons will be able to offer transplantations to
      all needy patients without undue delay. Donation from deceased or live human
      beings will become obsolete. Furthermore, it will be possible to alleviate graft
      rejection by genetic modification of the source animal.

PMID- 17445574
TI  - Human leukocyte antigen and its role in transplantation biology.
AB  - Human leukocyte antigens (HLA), the human version of the major histocompatibility
      complex (MHC), an integral part of maintenance of immune surveillance, have been
      widely studied for their roles in transplantation biology. A donor with an
      identical HLA system can donate tissue more successfully than the one who is not
      matched. The MHC is divided into class I, II, and III antigens; class I and II
      play important roles in transplantation immunology. HLA is codominantly expressed
      on chromosome 6 in every individual; HLA-A, -B, and -DR is known as the "haplo
      type." There are two sets of HLA antigens in each individual. Thus a child can
      inherit four different haplo-type combinations from parents. There is a 25%
      chance of totally matched or mismatched siblings and a 50% chance of half-matched
      siblings among a family with parents being a 50% match. The main purpose of HLA
      typing and lymphocyte crossmatching (LCM) in transplantation is to assess donor
      recipient immune compatibility and identify the presence of preformed donor
      specific cytotoxic alloantibodies in the recipient. It can be tested by serology
      or molecular techniques. We studied 8462 individuals for HLA typing by serology
      supplemented with molecular techniques (sequence-specific primers with low
      resolution). The common alleles were HLA-A19 (9.4%), -A1 (7.7%), -A2 (7.2%), -B5
      (10.2%), -B35 (6.6%), -B40 (5.3%), -DR2 (10.2%), -DR5 (7.5%), and -DR7 (5.1%).
      HLA typing and LCM testing support successful transplantation.

PMID- 17445575
TI  - Stem cell therapy-present status.
AB  - Stem cell research is a new field that is advancing at an incredible pace with
      new discoveries being reported from all over the world. Scientists have for years
      looked for ways to use stem cells to replace cells and tissues that are damaged
      or diseased. Stem cells are the foundation cells for every organ, tissue, and
      cell in the body. Stem cells are undifferentiated, "blank" cells that do not yet
      have a specific function. Under proper conditions, stem cells begin to develop
      into specialized tissues and organs. They are self-sustaining and can replicate
      themselves for long periods of time. Embryonic stem cells are pluripotent cells,
      isolated from the inner cell mass of the blastocyst-stage mammalian embryo. They
      have the ability to differentiate into several somatic or somatic-like functional
      cells such as neurons, hepatocytes, cardiomyocytes, and others. Adult stem cells
      are specialized cells found within many tissues of the body where they function
      in tissue homeostasis and repair. They are precursor cells capable of
      differentiation into several different cells. The knowledge of stem cells from
      various sources offered a new hope for the treatment of various diseases.

PMID- 17445576
TI  - Stem cells as a therapeutic modality in pediatric malformations.
AB  - AIM: The aim of this study was to explore stem cell use in congenital anomalies.
      PATIENTS AND METHODS: During July 2005 through July 2006, autologous stem cells
      were used in 29 patients: 12 with liver cirrhosis and 17 with meningomyelocele.
      Stem cells were injected into the hepatic artery and the portal vein or into the
      hepatobiliary radicals for liver cirrhosis, or into the spinal cord and caudal
      space for meningomyelocele. Preoperative status served as the control condition.
      OBSERVATIONS AND RESULTS: The ages of patients with liver cirrhosis ranged
      between 1.5 and 9 months (mean, 4.12 months). The etiology was extra hepatic
      biliary atresia (EHBA) versus neonatal cholestasis and choledochal cyst in 8; 2
      and 2 patients, respectively. Five patients died due to ongoing cirrhosis. Follow
      up at 3 to 12 months (N = 7) showed absence of cholangitis (4/7), yellow stools
      (5/7), decreased liver firmness (3/7), improved liver function (6/7), and better
      appetite (6/7). Hepatobiliary scan was excretory in 6 of 7 with improved uptake
      in 4 of 7. Histopathology demonstrated comparative improvement in fibrosis among
      3 patients. Meningomyelocele patients were between 0 and 1 month, 1-5 months, and
      1-4 years in 5, 8, and 2 cases respectively. Five had a history of rupture. Three
      had undergone meningocele repair in the past with neurological deficits. Redo
      surgery for a tethered cord was performed in 1 patient. Follow-up at 3 to 11
      months in 14 cases showed improved power in 7 with dramatic recovery in 3 (22%)
      and status quo in 7 (50%). CONCLUSION: Initial stem cell use in liver cirrhosis
      and meningomyelocele has suggested beneficial results. However, long-term
      evaluation in randomized controlled trials is essential to draw further
      conclusions.

PMID- 17445577
TI  - Hematopoietic stem cell transplantation in autoimmune diseases: the Ahmedabad
      experience.
AB  - INTRODUCTION: Autoimmune disease represents a (AD) breakdown of natural tolerance
      against autoreactive antigens leading to a high mortality and morbidity. The
      reaction is usually polyclonal; T- and B-cell components of the hematopoietic
      system are responsible for disease progression. Allogeneic/autologous
      hematopoietic stem cell transplantation (HSCT) are the current modalities for
      treating drug-resistant AD. PATIENTS AND METHODS: We present a single-center
      retrospective evaluation of allogeneic HSCT with nonmyeloablative, low-intensity
      conditioning in nine patients (five males, four females) with pemphigus vulgaris
      (PV) and 27 patients with systemic lupus erythematosus (SLE; 3 males, 24
      females). The mean follow-up period was 4.24 years for PV and 4.9 years for SLE.
      Cytokine-mobilized HSC from unmatched related donors, with mean dose of 21.3 x
      10(8) nucleated cells/kg body weight (BW; mean CD34(+) count, 6 x 10(6)/kg BW)
      was administered in to the thymus as well as the portal and peripheral
      circulations of recipients. Cyclosporine (4 +/- 1 mg/kg BW per day) and
      prednisolone (10 mg/kg BW per day) were administered for 6 months to protect
      mixed chimerism. A subset of patients with cross-gender donors were analyzed for
      peripheral blood chimerism at 1 month post-HSCT and every 3 months thereafter.
      RESULTS: Sustained clinical remission with peripheral lymphohematopoietic
      chimerism of 0.7 +/- 0.3% was observed in PV, whereas SLE relapsed after mean of
      7.35 months of disease-free interval associated with fall in chimerism from 5 +/-
      3% to < or =0.08 +/- 0.03%. CONCLUSION: HSCT was effective to achieve early
      clinical remission of PV; and in SLE relapsed after a 7.35-month disease-free
      interval accompanied by a fall in mixed lymphohematopoietic chimerism.

PMID- 17445578
TI  - Indian Transplant Registry-www.transplantindia.com.
AB  - The Indian Transplant Registry has been made possible due to the efforts of the
      Indian Society of Organ Transplantation (ISOT) over the past 5 years. The ISOT is
      about 20 years old and has more than 450 members related to multiorgan
      transplants with elected officers. It is in its first phase of development and is
      now available on the Web at www.transplantindia.com. The objective of developing
      this registry is to be able to view, collate, and audit the national data for all
      transplants in the country. In the first phase, "fast track" data are being
      captured with essential details of the program along with the yearly number of
      transplantations performed, the sex ratio, and type of transplantation. Over 10
      major institutions have submitted their data to the registry. In the second
      phase, over 20 fields would be captured; all member institutions would be
      encouraged to enter data prospectively. In the third phase, audit of the data
      would be possible. The members of the ISOT have been supportive and enthusiastic
      about the registry as reflected in their data submission to date.

PMID- 17445579
TI  - Organ donation and transplantation-the Chennai experience in India.
AB  - Tamil Nadu has been at the forefront of medical care in the country. It was the
      first state in the country that started a living kidney transplant program. It is
      also the first state to successfully start the cadaver programme after the
      passing of the "Transplantation of Human Organ Act" of 1994 and in the last 5
      years has formed a network between hospitals for organ sharing. From the year
      2000 to 2006 an organ sharing network was started in Tamil Nadu and the
      facilitator of this programme has been a non-government organization called MOHAN
      (acronym for Multi Organ Harvesting Aid Network) Foundation. The organs shared
      during the period number over 460 organs in two regions (both Tamil Nadu and
      Hyderabad). In Tamil Nadu the shared organs have included 166 Kidneys, 24 livers,
      6 hearts, and 180 eyes. In 2003 sharing network was initiated by MOHAN in
      Hyderabad and to some extent the Tamil Nadu model was duplicated. with some
      success and 96 cadaver organs have been transplanted in the last 3 years. There
      are many advantages of organ sharing including the cost economics. At present
      there is a large pool of brain dead patients who could become potential organ
      donors in the major cities in India. Their organs are not being utilized for
      various support logistics. A multi-pronged strategy is required for the long term
      success of this program. These years in Tamil Nadu have been the years of
      learning, un-learning and relearning and the program today has matured slowly
      into what can perhaps be evolved as an Indian model. In all these years there
      have been various difficulties in its implementation and some of the key elements
      for the success of the program is the need to educate our own medical fraternity
      and seek their cooperation. The program requires trained counselors to be able to
      work in the intensive cares. The government's support is pivotal if this program
      to provide benefit to the common man. MOHAN Foundation has accumulated
      considerable experience to be able to evolve a model to take this program to the
      national level and more so as it recently has been granted 100% tax exemption on
      all donations to form a countrywide network for organ sharing.

PMID- 17445580
TI  - Asian Indian donor marrow registry: All India Institute of Medical Sciences
      experience.
AB  - A major limitation in hematopoietic stem cell transplantation (HSCT) is the
      availability of a genetically matched donor, particularly with respect to the
      human leukocyte antigens (HLA)-linked immune response genes located on chromosome
      6 in humans. During the last 5 years, a total of 688 patients requiring HSCT
      underwent HLA testing in our department to identify a matched donor from their
      families. The sibship size ranged from 1 to > or =5 in all disease categories,
      except thalassemia major where the majority of patients had only 1 sibling.
      Family genotype analysis revealed that 39.3% of the total number of patients had
      an HLA-matched sibling and that families with sibship size of > or =4 had a
      higher probability (68.8%) compared with those with sibship size of < or =3
      (29.7%). Because the Indian population is characterized by the presence of novel
      HLA alleles and unique haplotypes (HLA-A*0211, B*2707, A*26-B*08-DRB1*03),
      patients with rare HLA alleles have much less probability of finding an unrelated
      optimally matched donor than those with common HLA phenotypes. Smaller family
      size and unique HLA profile are limitations that can be overcome by developing
      unrelated volunteer marrow donor registries. The Asian Indian Donor Marrow
      Registry at our institute is regularly providing services to such patients.

PMID- 17445581
TI  - Cadaveric renal transplantation: our experience at the Institute of Kidney
      Diseases & Research Centre, Institute of Transplantation Sciences, Ahmedabad.
AB  - In a developing country such as India, cadaveric renal transplantation accounts
      for only less than 1% of total renal transplantations. The reasons for such a low
      rate of cadaveric transplantation are many, ranging from lack of awareness to
      socioeconomic reasons. Our institute conducted a statewide public awareness
      program and initiated an intercity organ harvesting program. This doubled the
      cadaveric renal transplantations in the last 2 years. We performed 38 cadaveric
      transplantations among 190 renal transplantations in the last year (August 2005
      to July 2006). We retrieved kidneys from 21 donors, of whom 9 were outside our
      city. From 21 donors we transplanted 38 recipients; out of whom 3 received dual
      kidneys and one kidney was discarded. The Mean age of the donors was 41.4 +/-
      18.2 years with a mean cold ischemia time of 6.9 +/- 3.8 hours. Sixty-eight
      percent had delayed graft function. At the last follow-up, which was 190 +/- 98
      days, patient survival rate was 90%: 4 patients died, including 2 due to
      bacterial sepsis and 2 due to cytomegalovirus (CMV) disease. The Graft survival
      rate was 85%, and the death-censored graft survival rate was 90%. Mean serum
      creatinine value at the last follow-up was 1.2 +/- 0.3 mg%. There were 5 episodes
      of acute rejection in 31 patients during first 3 months (16% acute rejection
      rate). The increase in cadaveric transplantations was associated with
      satisfactory patient and graft survival despite the high incidence of delayed
      graft function.

PMID- 17445582
TI  - Impact of retroperitoneoscopic donor nephrectomy on renal allograft in Indian and
      African recipients.
AB  - AIM: To evaluate the impact of laparoscopic donor nephrectomy on renal allografts
      in Indian and African recipients. MATERIAL AND METHODS: Between September 2004
      and August 2006, 125 retroperitoneoscopic donor nephrectomies were performed.
      Ninety-four donors were Indian (group A) and 32, African (group B). Three ports
      were used for left-sided and four for right-sided surgery, respectively. Hem-o
      lok clips were used to control arteries and veins on left side and arteries on
      right side while an Endo-TA stapler was used on the right side to obtain an
      inferior vena caval cuff. RESULTS: The mean operative times in groups A and B
      were 130 and 134 minutes; mean blood loss, 100.4 mL and 85.3 mL; and mean warm
      ischemia time, 242.1 seconds and 234.5 seconds, respectively. Recipient mean
      serum creatinine value on day 7 was 1.9 and 1.6 mg%, and on day 28, 1.44 mg% and
      1.4 mg%, respectively. CONCLUSION: Early adequate allograft function following
      retroperitoneoscopic donor nephrectomy was comparable in African and Indian
      patients, suggesting that no racial advantage was observed in this procedure.

PMID- 17445583
TI  - Transplantation from non-heart-beating donors.
AB  - Non-heart-beating donor (NHBD) transplants have been reintroduced into clinical
      practice because of the progressively rising number of patients on the transplant
      waiting list and relatively static numbers of cadaver organ donors. Several units
      have undertaken NHBD programs utilizing category 3 of Maastricht criteria. The
      current data show encouraging outcomes, which give rise to further interest in
      this donor pool. This manuscript briefly summarizes the most recent reports in
      this field.

PMID- 17445584
TI  - Opportunistic infections in renal allograft recipients.
AB  - Two major factors for successful organ transplantation are better control of
      rejection and better prevention and treatment of infections. In renal allograft
      recipients, immunosuppressive drug therapy is the major cause of
      immunocompromised status and occurrence of infections, which arise most commonly
      as a result of invasion by endogenous opportunists. It may also follow
      colonization by exogenous environmental organisms and via transfer of
      cytomegalovirus along with the transplanted kidney. The overall incidence of
      opportunistic infections varies from center to center; up to 15% of renal
      transplant recipients die of these infections. Clinical signs and symptoms of
      infection in immunocompromised patients may be concealed or imitated by the
      underlying disease, and a high index of clinical suspicion is vital. The unusual
      pathogens encountered in these patients demand thorough investigation. A total of
      84 opportunistic infections encountered in renal allograft recipients during
      histopathologic and cytopathological evaluation of various specimens during the
      last 15 years is presented in this report. Invasive fungal infections were the
      most common pathogens, amounting to 55% of all infections. The dramatic increase
      in the diversity and number of opportunistic infections detected in these
      patients is not only due to an increasing population of susceptible individuals
      but also due to an improved recognition by advanced laboratory diagnostic
      techniques. The success of management of opportunistic infections depends on
      strong clinical suspicion, early diagnosis, and prompt treatment. The challenges
      of early diagnosis of opportunistic infections and prompt treatment are great;
      the rewards are even greater.

PMID- 17445585
TI  - Recurrent glomerulopathy in the renal allograft.
AB  - The renal allograft is prone to develop almost all forms of glomerular diseases
      either as recurrent or de novo disease, with the exception of Alport's syndrome.
      Identification of recurrent glomerulonephritis requires an accurate diagnosis of
      pretransplant disease, which may not always be possible as it presents as end
      stage renal disease at the time of transplantation. Posttransplantation
      glomerular diseases such as chronic allograft nephropathy, malignant
      hypertension, and thrombotic microangiopathy due to various causes may be
      mistaken for primary glomerulonephritis. In this article, an attempt has been
      made to identify the glomerular diseases that were detected in renal allografts
      over a 9-year period, comprising 950 cases in a tertiary care center in north
      India.

PMID- 17445586
TI  - Focal segmental glomerulosclerosis and renal transplantation.
AB  - Primary focal segmental glomerulosclerosis (FSGS) is a major cause of nephrotic
      syndrome and eventual end-stage renal disease. It is known to be due to an
      abnormality of the visceral epithelial cells (podocytes) of the glomerulus. The
      morphological hallmark of primary FSGS is diffuse effacement of podocyte foot
      processes. The etiology of the podocyte damage is not been clearly established.
      FSGS can also be a secondary process due to underlying conditions including
      obesity and heroin use. In the secondary processes, the mechanism appears to be a
      decreased ratio of podocytes to the glomerular filtration surface area. Familial
      forms of FSGS also exist due to alterations of several different podocyte
      proteins. Primary FSGS is an increasing cause of end-stage renal disease.
      Recurrence of severe FSGS in renal allograft recipients presents a major
      challenge to transplant physicians. The incidence of recurrence is generally
      accepted to be between 20% and 30%. Risk factors for and characteristics of
      recurrence include a rapid progression of the primary disease to end-stage renal
      failure, early onset of nephrotic range proteinuria after allografting, frequent
      loss of the allograft, a high frequency of recurrence in subsequent allografts,
      and children less than 15 years of age. Some investigators have identified a
      circulating factor called the FSGS factor that appears to be associated with
      recurrence after transplantation. This factor has been shown to be a protein
      between 30 and 50 kd molecular weight. Logically, the possibility of a
      circulating factor associated with recurrence of FSGS led investigators to treat
      patients with plasmapheresis. Several studies have been reported with varying
      success. The response of patients to plasmapheresis seems to be completely
      individual. Other studies have added cyclophosphamide and/or mycophenolate
      mofetil to the plasmapheresis protocol. Again success in these studies has been
      variable. However, because some patients show complete recovery with
      plasmapheresis, individuals who develop recurrent FSGS after transplantation
      usually are given a trial of plasmapheresis therapy.

PMID- 17445587
TI  - Significance of anti-HLA and donor-specific antibodies in long-term renal graft
      survival.
AB  - Numerous studies have demonstrated an association of posttransplant HLA
      antibodies with decreased long-term graft survival. The presence of C4d
      deposition in these cases supports the hypothesis that antibody and complement
      deposition are involved in the pathogenesis of graft failure. Development of HLA
      antibodies may predate the clinical manifestation of chronic rejection (CR).
      However, frequency of donor-specific antibody is low when all patients are
      screened regardless of their graft function, and it may be more valuable to look
      for antibody only in patients with mild dysfunction. Effective treatment for CR
      has not been identified, although increased immunosuppression has been shown to
      decrease antibody levels and stabilize graft function. Many patients have been
      identified with good graft function despite the presence of circulating donor
      specific HLA antibody. Additional studies focusing on the mechanism behind the
      apparent protection from the detrimental effects of antibody in such patients are
      needed.

PMID- 17445588
TI  - Tacrolimus (Pan Graf) in live related renal transplantation: an initial
      experience of 101 recipients in India.
AB  - BACKGROUND: Success of modern transplantation is in large part due to the
      successful development of effective immunosuppressive agents. The safety and
      efficacy of tacrolimus in transplantation is well established. However,
      tacrolimus (Pan Graf, Panacea Biotec Ltd, India) has only been available in India
      for the last 2 years. This study was conducted to assess the safety and efficacy
      of tacrolimus in live related kidney transplantation. We report an initial
      experience of tacrolimus as de novo therapy in a live related renal
      transplantation program. MATERIALS AND METHODS: One hundred one consecutive
      recipients of a live renal allograft were commenced on triple immunosuppression
      consisting of tacrolimus, mycophenolate mofetil or azathioprine, and steroids.
      The dose of tacrolimus was adjusted to keep trough levels at 10-12 ng/mL in the
      first 3 months, 8-10 ng/mL in the next 3 months, and 5-8 ng/mL thereafter. All
      patients were followed up for a period ranging from 4 weeks to 24 months. The
      effect of this regimen on the incidence of graft rejection, graft survival,
      patient survival, and new-onset diabetes mellitus was evaluated. Any evidence of
      graft dysfunction was evaluated using a graft biopsy. RESULTS: There were 89 male
      and 12 female patients with mean age of 32.08 years. The incidence of acute
      rejection was 3.96%; 21.05% developed new-onset diabetes mellitus. Six patients
      were diabetic prior to transplantation and 9 patients were hepatitis C virus
      (HCV)-positive; 77.7% of HCV-positive patients and 15.1% of HCV-negative patients
      developed posttransplantation diabetes mellitus. The patient survival rate at the
      current follow-up was 92.07%. No graft was lost due to rejection. CONCLUSION:
      Tacrolimus is a safe and effective immunosuppressant in live related renal
      transplantation.

PMID- 17445589
TI  - Effect of bisphosphonates on bone mineral density after renal transplantation as
      assessed by bone mineral densitometry.
AB  - INTRODUCTION: Steroid-induced osteoporosis is a major problem after organ
      transplantation. There is considerable evidence that bisphosphonates are
      effective in decreasing osteoporosis. AIM: This prospective study was carried out
      to see the effects of bisphosphonates on bone mineral density (BMD) after
      successful renal transplantation. MATERIAL AND METHODS: Fifty consecutive
      patients of successful renal transplantation were randomized into two groups.
      Group A (n = 27) received 35 mg/wk of Alendronate for 6 months after
      transplantation. Group B (n = 23) did not receive Alendronate and served as a
      control. Both groups underwent a pretransplant baseline dual-energy X-ray
      absorptiometry (DEXA) scan of their hips and lumber spines. Both groups received
      oral calcium and vitamin D supplement. Both groups were matched for the regimen
      and dose of immunosuppressive drugs. BMD was measured at 3 months and 6 months
      after transplantation. RESULTS: Both groups showed a decline in BMD in early
      months posttransplantation. However, the 6-month DEXA scans showed a significant
      rise in BMD in group A as compared to group B. CONCLUSION: Bisphosphonates appear
      to have a beneficial effect on steroid-induced bone loss.

PMID- 17445590
TI  - Growth in pediatric renal transplant recipients.
AB  - One of the fundamental challenges in managing pediatric renal transplant
      recipient is to ensure normal growth and development. The goal of renal
      transplant is not just to prolong life but to optimize quality of life. Short
      stature during childhood may be associated with academic underachievement and
      development of comorbidities such as attention deficit hyperactivity disorder,
      learning disability, and mood disorders. The most important factors affecting
      growth are use of corticosteroids, allograft function, and age and height deficit
      at the time of transplant. Aggressive conservative management of chronic renal
      failure and early use of growth hormone therapy will help in optimizing height at
      time of transplant. Early transplant, steroid minimization or withdrawal, and
      growth hormone therapy will help in achieving normal adult height in a majority
      of renal post transplant population. Steroid avoidance to achieve good growth
      still needs to be validated.

PMID- 17445591
TI  - Challenge of tuberculosis in renal transplantation.
AB  - There is very high incidence of tuberculosis (TB) in dialysis and renal
      transplant (RT) recipients in developing countries. Clinical manifestation of TB
      may be atypical or obscure in initial stages. Common clinical abnormalities
      include pyrexia, pulmonary infiltrates, exudative pleural effusion, and exudative
      ascites. Aggressive investigations must be done in patients with pyrexia,
      pulmonary abnormalities, scanty sputum, and weight loss. BAL and computed
      tomography (CT) scan of the chest should be done in such cases. Tuberculin skin
      test is not helpful in the majority of patients. New blood tests to quantitate
      PPD reactivity in vivo and tests to distinguish between latent M tuberculosis
      infection from BCG-induced reactivity have been devised recently. Side effects of
      anti-TB drugs, especially hepatitis, need close observation because of the
      frequent occurrence of viral hepatitis in such cases. Tests to confirm latent TB
      are desirable before starting chemoprophylaxis in RT recipients. INH prophylaxis
      cannot be recommended universally in all RT recipients.

PMID- 17445592
TI  - Monitoring of anti-HLA and anti-Major histocompatibility complex class I related
      chain A antibodies in living related renal donor transplantation.
AB  - This study was undertaken with the aim to analyze the clinical relevance of
      posttransplant anti-HLA and anti-major histocompatibility complex class I related
      chain A (MICA) antibodies in response to living related donor renal
      transplantation. A total of 185 consecutive post-renal transplant recipient serum
      samples were analyzed for the detection of anti-HLA and MICA antibodies using
      enzyme-linked immunosolvent assay techniques. Patients carrying both anti-HLA as
      well as anti-MICA antibodies (MICA(+)/HLA(+)) were the worst affected, showing
      significantly poorer graft survival compared with the MICA-/HLA-negative group
      (17% vs 89%, chi(2) = 19.63, P = .000). Similarly, patients with only MICA
      antibodies or those with only HLA antibodies also had significantly lower graft
      survival (P = .035 and P = .001, respectively) as compared to the nonsensitized
      group. The study illustrated that posttransplant monitoring antibodies to both
      MICA as well as HLA could be good predictors of renal allograft failure.

PMID- 17445593
TI  - Management of calculi in a donor kidney.
AB  - INTRODUCTION: We evaluated the safety and efficacy of ex vivo ureteroscopy
      (ExURS) and extracorporeal shock wave lithotripsy (ESWL) as means of rendering a
      donated kidney stone-free in living related and deceased donor renal
      transplantation. MATERIAL AND METHODS: Three cases with calculi in donor kidneys
      were managed; 1 was from a living related donor and 2 were from deceased donors.
      Immediately after cold perfusion, ExURS was performed with iced saline solution
      in 2 cases. Access to the collecting system was via the ureteral stump. Calculi
      were fragmented with pneumatic intracorporeal lithotripsy and fragments were
      removed with forceps. Posttransplantation ESWL was given to 1 patient for
      migration of a small lower caliceal calculus in the upper ureter in 1 allograft
      of a dual-kidney transplantation. RESULTS: Access to the renal collecting system
      and stone fragmentation was technically successful in both cases. Indwelling
      ureteral stents were kept during transplantation in all cases. There were no
      intraoperative or postoperative ureteral complications. Following ESWL, stone was
      fragmented and cleared on its own within a week. At mean follow up of 2.2 years
      no new stone formed in any recipient or donor. CONCLUSIONS: ExURS was technically
      feasible to render a stone-bearing kidney stone- free without compromising
      ureteral integrity or renal allograft function. ESWL could be performed at a
      later date.

PMID- 17445594
TI  - Transplant arteriopathy.
AB  - Renal allograft rejection is classified based upon its time of onset and
      vulnerability to therapeutic reversal as hyperacute, acute, and chronic
      rejection. However, this classification has certain limitations, like the
      nomenclature of acute rejection despite the fact that it can occur any time after
      transplantation. Similarly, the onset of lesions characteristic of chronic
      rejection may appear very early, even as soon as 2 to 4 weeks posttransplant.
      Apparently the process of acute/chronic rejection does not follow a protracted
      time course; instead, the process can be ongoing, regardless of chronology.
      Another way of classifying various types of rejection may be in terms of
      different mediators that are involved in effecting each of the phenomena. This
      schema of classification based on pathogenetic mediators of rejection may help in
      evolving strategies for treatment targeted to specific mechanisms of rejection.

PMID- 17445595
TI  - Polyclonal antibodies in renal transplantation--a relook.
AB  - Polyclonal antibodies have been used in renal transplantation for the past four
      decades. Increasing knowledge regarding their varied mechanisms of action have
      confirmed their versatility in clinical practice. They can be used for induction,
      reversing acute rejections (especially those resistant to steroids), and possibly
      conferring an element of allotolerance, thereby reducing chronic allograft
      nephropathy. Their recent usage as IV bolus, single-dose, preoperative infusion
      as induction therapy in renal transplantation is an attractive and extremely cost
      effective strategy, especially in a developing country such as India.

PMID- 17445596
TI  - Chronic rejection: an enduring enigma of transplantation biology.
AB  - Renal transplantation has achieved reasonably good success over the years in
      controlling acute rejection episodes; however, the immunology of chronic
      rejection is still not well understood. The problem haunts transplanters across
      the globe. We describe the presentation, brief immunopathological events, and
      recent advances suggested by pathologists to define chronic rejection and
      differentiate it from chronic allograft nephropathy. Our experience using
      tolerance induction is briefly mentioned including a reduced incidence of acute
      rejection episodes, chronic rejection events, or calcineurin inhibitor toxicity
      using lower drug levels.

PMID- 17445598
TI  - Research news and notes.

PMID- 17445599
TI  - Microneurosurgical management of middle cerebral artery bifurcation aneurysms.
AB  - BACKGROUND: Of the MCA aneurysms, those located at the main bifurcation of the
      MCA (MbifA) are by far the most frequent. The purpose of this article is to
      review the practical anatomy, preoperative planning, and avoidance of
      complications in the microsurgical dissection and clipping of MbifAs. METHODS:
      This review, and the whole series on intracranial aneurysms, is mainly based on
      the personal microneurosurgical experience of the senior author (JH) in 2 Finnish
      centers (Helsinki and Kuopio), which serve without patient selection the
      catchment area in southern and eastern Finland. RESULTS: These 2 centers have
      treated more than 10,000 patients with intracranial aneurysm's since 1951. In the
      Kuopio Cerebral Aneurysm Data Base of 3005 patients with 4253 aneurysms, MbifAs
      formed 30% of all ruptured aneurysms, 36% of all unruptured aneurysms, 35% of all
      giant aneurysms, and 89% of all MCA aneurysms. Importantly, in 45%, rupture of
      MbifA caused an ICH. CONCLUSIONS: Middle cerebral artery bifurcation aneurysms
      are often broad necked and may involve one or both branches of the bifurcation
      (M2s). The anatomical and hemodynamic features of MbifAs make them usually more
      favorable for microneurosurgical treatment. In population-based services, MbifAs
      are frequent targets of elective surgery (unruptured), acute surgery (ruptured),
      and emergency surgery (large ICH), even advanced approaches (giant). The
      challenge is to clip the neck adequately, without neck remnants, while preserving
      the bifurcational flow.

PMID- 17445600
TI  - Microsurgical treatment of unruptured intracranial aneurysms. A consecutive
      surgical experience consisting of 450 aneurysms treated in the endovascular era.
AB  - BACKGROUND: With the progressive refinement of endovascular techniques, fewer IAs
      are being treated with open microsurgery. There is limited information regarding
      the impact of this trend on the ability of younger neurosurgeons to achieve
      proficiency in the surgical management of IAs. We describe a consecutive series
      of patients with unruptured IAs treated by a neurosurgeon initiating a dedicated
      cerebrovascular practice in the "endovascular era." METHODS: We retrospectively
      reviewed the records of all patients who had undergone surgical repair of a
      saccular IA by one neurosurgeon upon completion of neurosurgical training in July
      1997 until April 2005. Patients with ruptured IAs were excluded from review.
      RESULTS: Of the 1450 patients with IAs treated during this period, 376 underwent
      microsurgical repair of 450 unruptured IAs. Microsurgical aneurysm neck clipping
      was possible in most cases, although distal revascularization with proximal
      occlusion was used in many of the more complicated aneurysms. Major complications
      occurred in 6 (1.60%) patients, and 1 (0.27%) patient died. At the time of 6
      month follow-up, 4 (1.06%) patients were left with a new focal neurologic deficit
      related to surgery. CONCLUSIONS: Despite the growing role of endovascular therapy
      in the management of IAs, it is possible for young neurovascular surgeons to
      achieve acceptable results with open microsurgical treatment of IAs. The factors
      that were deemed important in achieving success in this series included a
      collaborative approach with endovascular colleagues, careful surgical judgment,
      continual reanalysis of personal results, and early support from experienced
      mentors.

PMID- 17445605
TI  - Carotid endarterectomy in the elderly: are the patient characteristics, the early
      outcome, and the predictors the same as those in younger patients?
AB  - BACKGROUND: The study was conducted to detect possible differences in patient
      characteristics, in early outcome, and in predictors for 30-day combined stroke
      and death rate between younger and older patients undergoing CEA. METHODS:
      Between March 1988 and November 2005, we recorded prospectively the data from
      every patient who underwent carotid artery surgery. Cardiovascular risk factors,
      comorbidities, anesthetic and surgical techniques, outcome, and survival were
      reviewed and compared between <75 age and >or=75 age group. RESULTS: We performed
      1028 procedures in 742 patient. A total of 286 carotid endarterectomies were done
      in 213 patients 75 years or older. The number of cardiovascular risk factors per
      patient decreased with age. The risk factors tobacco use, hyperlipidemia, and the
      combination tobacco, hypertension, and hyperlipidemia were predominant in the
      younger group. Hypertension as only risk factor and the combination hypertension
      and hyperlipidemia were more present in the older group. The perioperative
      combined minor and major stroke and death rate was 2.8% in both groups. Attendant
      predictors for adverse outcome in the >or=75 age group were female sex and the
      combination of the risk factors diabetes, tobacco use, and hypertension.
      CONCLUSIONS: The type, the number, and the combinations of cardiovascular risk
      factors and the predictors for adverse outcome are different in the 2 age groups.
      Our observations indicate that people 75 years or older with small number of
      cardiovascular risk factors can undergo CEA with the same risk of perioperative
      stroke and death as the younger patients.

PMID- 17445607
TI  - Tentorial dural arteriovenous fistulas.
AB  - BACKGROUND: Tentorial dural arteriovenous fistula is uncommon but is a life
      threatening lesion. We present our experience with 5 patients with TDAVFs, review
      the relevant literature, and present the rationale of our current management
      strategy. METHOD: The data of 5 patients with TDAVFs treated in Huashan Hospital,
      Shanghai, China, between June 2002 and May 2003 were reviewed retrospectively,
      including their illness history, neuroimaging, operation records, and follow-up
      data. RESULTS: There were 3 females and 2 males with ages from 25 to 52 years
      (average, 38 years). Clinical manifestations were acute SAH in 2 patients and
      progressive neurologic deficits in 3 patients. Magnetic resonance imaging and DSA
      were major diagnostic and follow-up modalities. All cases belonged to Borden
      classification type 3. A tentorial marginal type was present in 3 cases, a
      tentorial lateral type in 1 case, and a tentorial medial type in 1 case.
      Preoperative transarterial embolization was done in 3 patients. All patients
      underwent craniotomy with the coagulation of the fistulas and surrounding
      tentorial dura mater, and the disconnection of leptomeningeal venous drainage.
      The surgical approaches were via transanterior petrous approach in 3 cases,
      subtemporal intradural approach in 1 case, and unilateral occipital and
      transtentorial approach in 1 case. All patients had clinical improvement. There
      was no surgical mortality and morbidity. Postoperative DSA confirmed obliteration
      of TDAVFs in 3 cases; MRI demonstrated the thrombosis of venous aneurysm and
      disappearance of previous brainstem edema in 1 case, and partial thrombosis of
      venous aneurysm in another case. Follow-up study ranging from 2 to 3 years
      (average, 2.5 years) showed no recurrence, and all patients have resumed their
      normal activities. CONCLUSIONS: Tentorial dural arteriovenous fistulas are
      aggressive vascular lesions causing SAH and progressive neurologic deficits.
      Prompt diagnosis and definite treatment are mandatory. Obliteration of the
      fistulas and/or leptomeningeal venous drainage should be the goal of treatment.
      Microsurgical procedures with/without endovascular intervention are the best
      choice of treatment.

PMID- 17445610
TI  - Intra-arterial verapamil-induced seizures: case report and review of the
      literature.
AB  - BACKGROUND: Intra-arterial verapamil infusion with or without balloon angioplasty
      is a common therapy for patients with hypertensive, hypervolemic, and nimodipine
      refractory vasospasm following aSAH. Seizures occurring from IA infusion of
      verapamil are rare. CASE DESCRIPTION: A 24-year-old Korean-American woman
      presented with aSAH from the rupture of a 5-mm ICA bifurcation aneurysm. The
      aneurysm was secured with clip ligation through a craniotomy, and the patient was
      treated with HHH therapy in the neurosurgical ICU. Routine postoperative cerebral
      angiography was performed to confirm occlusion of the treated aneurysm and assess
      for vasospasm. In the first angiogram, vasospasm was detected in the supraclinoid
      portion of the ICA. Intra-arterial verapamil was started; during this treatment,
      the patient developed right-sided focal motor seizures. The infusion was
      terminated and the seizures were halted with midazolam. The patient's course was
      unremarkable until postoperative day 7, when she developed expressive aphasia,
      for which she was taken for emergent cerebral angiography under anesthesia.
      Marked focal spasm was identified in the distal supraclinoid ICA and the left A1.
      The patient was treated with 25 mg of superselective verapamil infusion. Upon
      emerging from anesthesia, her aphasia had resolved; however, 90 minutes after
      angiography, she experienced generalized seizures while she was in the ICU.
      CONCLUSIONS: Seizures are a rare complication during cerebral angiographic
      procedures. Intra-arterial verapamil-induced seizures are infrequently reported.
      Cognizance for the potential of seizures to occur is advised during verapamil
      infusion for the treatment of refractory vasospasm in certain individuals.

PMID- 17445612
TI  - Intracranial arteriovenous malformations treated with linear accelerator-based
      conformal radiosurgery: clinical outcome and prediction of obliteration.
AB  - BACKGROUND: Little is written about the clinical outcome and predictor factors of
      obliteration and treatment success in patients with intracranial AVMs treated
      with LINAC-based conformal radiosurgery in Mexican institutions. METHODS: We
      analyzed 40 patients with intracranial AVMs with a mean follow-up of 29 (range,
      23-34) months. Seven AVMs (17.5%) had a volume <1 cm(3); 10 (25%), 1 to 4 cm(3);
      13 (32.5%), 4.1 to 10 cm(3); and 10 (25%), >10 cm(3). The mean prescription dose
      was 15.4 Gy. Twenty-six patients (68%) presented hemorrhage before treatment; 4
      (10%), chronic headache; 14 (35%), seizures; and 3(8%), neurologic deficit.
      RESULTS: Seven patients (17.5%) underwent objective clinical improvement. Thirty
      patients (75%) remained without clinical changes. Three patients (7.5%) developed
      edema and 1 (2.5%) had a rebleeding after treatment. Twenty-five patients (63%)
      presented complete obliteration of the AVM. A successful treatment (obliteration
      without a new deficit) was obtained in 23 (58%) of the cases. The percentage of
      obliteration was in <1 cm(3) (86%), 1 to 4 cm(3) (80%), 4.1 to 10 cm(3) (54%),
      and >10 cm(3) (40%), without a significant difference between groups (P = .1).
      Patients with RBAS of <or=1.9 had an obliteration of 79% and, those with >1.9,
      48%; the successful treatment in the former resulted in 79% and, in the latter,
      38% (P = .08 and P = .02, respectively). CONCLUSIONS: The clinical outcome was
      similar to other series. The RBAS seems to be a good predictor of obliteration
      and successful treatment in patients with AVMs treated with LINAC-based conformal
      radiosurgery.

PMID- 17445614
TI  - Sponge pieces as retractors in neurosurgical interventions.
AB  - BACKGROUND: Different retractors including high-technology products were proposed
      for neurosurgical interventions. The sponge, having characteristics of
      deformability and resistance to compression, might be an alternative retractor
      for the neurosurgical era. METHODS: Sponge obtainable from the ordinary market
      was broken into pieces and sterilized by ethylene oxide. During intervention, the
      appropriate sponge pieces were applied inside the dissected sulci for the purpose
      of retraction. RESULTS: The sponge pieces were easily applied and supplied
      optimal retraction during operations. Proximal application to the dissected
      sylvian fissure enabled the exposure of the inner distal part including the
      insular surface, whereas application between the frontobasal surface and the
      orbital roof provided satisfactory exposure of the suprachiasmatic area. The
      retraction capacity of the sponge was less than that of self-retaining Leyla
      retractors, but the postoperative appearance of cortical surfaces was fine
      without any bruising or hyperemia. CONCLUSION: The sponge material, with its
      inner mechanical characteristics and ease of application like cotton pads, seems
      to be an alternative retractor in neurosurgical interventions, and these
      characteristic may inspire development of new high-technology retractors.

PMID- 17445615
TI  - Future of endoscopy in neurosurgery.

PMID- 17445616
TI  - Retropharyngeal cerebrospinal fluid collection as a cause of postoperative
      dysphagia after anterior cervical discectomy.
AB  - BACKGROUND: Transient dysphagia after anterior cervical discectomy is not
      uncommon. It is usually related to esophageal edema secondary to retraction,
      mechanical adhesions of the esophagus to the anterior spine, and stretch injuries
      to nerves involved in the swallowing mechanism. Structurally induced dysphagia,
      secondary to laceration of the neck viscera or to the presence of retropharyngeal
      masses, is by far less frequent, and it does not usually improve over time. CASE
      DESCRIPTION: The authors present the case of a 36-year-old woman who complained
      of severe dysphagia both for solids and liquids after C4 through C5 anterior
      discectomy and fusion, complicated by a millimetric dural tear of the anterior
      thecal sac. Postoperative neuroimaging revealed retropharyngeal fluid collection,
      extending in front of the vertebral bodies of C3, C4, and C5, exerting a mass
      effect on the posterior wall of the pharynx. Taking into account both the MRI
      aspect of the collection and the dramatic improvement of symptoms after lumbar
      punctures, we conducted a diagnosis of CSF collection in continuity with the
      subarachnoid space. The dysphagia and the CSF collection resolved with
      conservative therapy (bed rest and 3 lumbar punctures). CONCLUSION: To the best
      of our knowledge, such a complication has never been described before in the
      literature. It should be included in the differential diagnosis of patients with
      postoperative dysphagia lasting more than 48 hours.

PMID- 17445618
TI  - Bilateral high-level percutaneous cervical cordotomy in cancer pain due to lung
      cancer: a case report.
AB  - BACKGROUND: Computed tomography-guided high-level percutaneous cordotomy has been
      used unilaterally or bilaterally for the treatment of localized intractable pain
      in malignancies. CASE DESCRIPTION: A 57-year-old man was admitted to the hospital
      with the complaint of intractable pain involving the left side of the chest,
      axillary region, and shoulder. He was operated for small cell lung cancer on the
      left side in December 2003 and received radiotherapy and chemotherapy. His
      neurological examination was normal. Magnetic resonance imaging of the thorax
      revealed contrast-enhancing lesions on the left side extending to mediastinum and
      pleura. His pain was relieved completely after the first cordotomy procedure, and
      he was discharged from the hospital on the second postoperative day. The patient
      was readmitted to the hospital with the complaint of severe unilateral chest pain
      like the initial pain on the right side 4 days after cordotomy. The CT-guided
      bilateral high-level percutaneous cordotomy was performed with a 15-day interval.
      CONCLUSION: The CT-guided bilateral high-level percutaneous cordotomy can be used
      in the treatment of intractable upper trunk pain in patients with cancer without
      pulmonary dysfunction.

PMID- 17445619
TI  - Adrenal insufficiency secondary to glucocorticoid withdrawal in patients with
      brain tumor.
AB  - BACKGROUND: Glucocorticoids are the main drug used to control vasogenic edema in
      patients with brain tumor. Rapid GC tapering may not only decompensate
      intracranial pressure, but also unmask SAI, and some symptoms of SAI can be
      mistakenly attributable to increased intracranial pressure or side effects of
      chemotherapy and radiation therapy. METHODS: The University of Virginia Neuro
      Oncology Database was reviewed from February 2002 to January 2006, and 5 neuro
      oncology patients with clinical and laboratory evidence of SAI were identified.
      RESULTS: In our experience, 1% of neuro-oncology patients treated with GC
      developed SAI. Symptoms resembled increased intracranial pressure or side effects
      of antineoplastic treatment. CONCLUSION: A healthy index of suspicion for this
      complication and use of pharmacologic testing will help avert misattribution of
      symptoms of SAI and its deleterious consequences.

PMID- 17445620
TI  - Thalamomesencephalic ossified cavernoma presenting with Holmes' tremor.
AB  - BACKGROUND: Midbrain cavernoma associated with Holmes' tremor is a rare entity.
      Although there have been 4 other cases of Holmes' tremor caused by a cavernoma,
      this is the first case that was cured by surgical removal of the cavernoma. In
      addition, heavy ossification and Holmes tremor as a clinical presentation are 2
      unusual features of the cavernoma. Possible mechanisms of these very rare
      entities are discussed in relation to the present report and relevant literature
      is reviewed. CASE DESCRIPTION: We present a case of 60-year-old woman with
      heavily ossified cavernoma of the thalamomesencephalic junction with neuroimaging
      and histologic features. The only manifestation was Holmes' tremor. The patient
      was operated on via posterior interhemispheric approach while in the sitting
      position. After the arachnoid folds of the quadrigeminal cistern were opened, the
      thin neural tissue on the surface of the dorsal midbrain was incised and the
      lesion was visualized and totally removed as a single piece. The tremor was
      almost completely suppressed. CONCLUSION: Ossified cavernoma is a rare entity but
      has a characteristic MRI appearance. It should be considered in the differential
      diagnosis of intracerebral hypointense lesions on both T1- and T2-weighted MR
      images because they are potentially curable by surgical removal.

PMID- 17445623
TI  - Delayed development of frontal mucocele after fronto-orbital advancement in a
      child with craniosynostosis.
AB  - BACKGROUND: Sinus mucoceles rarely develop as a consequence of inadequate sinus
      ventilation that arises due to inflammation, allergy, polyps, tumors, surgery,
      and trauma. The development of frontal sinus is delayed until older than 6 years.
      Therefore, the development of the mucocele in the frontal sinus after fronto
      orbital advancement surgery in young children with craniosynostosis may provide
      essential information for the development of the frontal sinus. CASE DESCRIPTION:
      We report a rare case of a 22-year-old man presenting with a frontal mucocele
      manifested by dull headache, proptosis, and diplopia, and which developed 16
      years after fronto-orbital advancement surgery for craniosynostosis. Magnetic
      resonance imaging demonstrated that a multiple cystic mass extended from the
      frontal sinus to the retro-orbital space along the optic nerve. During surgery,
      we found that the cyst consisted of mostly thin, yellow mucosa, which developed
      from an anomalously overdeveloped frontal sinus containing yellow pus-like
      intracystic fluid. There was no gross local invasion by the cyst. We easily
      dissected and removed the mucosal cyst from the large frontal sinus completely
      with frontal sinus obliteration. We cranialized the anomalously large frontal
      sinus by removal of the posterior wall of the frontal sinus and then widening the
      ethmoidal drainage with endoscopic ethmoidectomy. CONCLUSION: We report the first
      case of a frontal sinus mucocele that developed after fronto-orbital advancement
      surgery in the literature and suggest that the mucocele development after fronto
      orbital advancement supports the hypothesis of frontal bone-inducing role in
      frontal sinus development.

PMID- 17445624
TI  - Benign angiopathy of the central nervous system presenting with intracerebral
      hemorrhage.
AB  - BACKGROUND: Primary central nervous system vasculitis has traditionally been
      described as an aggressive condition, with significant morbidity and mortality. A
      subgroup of patients has been identified who have a similar clinical
      presentation, but with a benign course. This syndrome of BACNS is successfully
      treated with low-dose steroids and calcium-channel blockers. Histologic
      confirmation, when performed, is normal. METHODS: Intracerebral hemorrhage is a
      rare presenting finding in the setting of BACNS. We present 2 patients with acute
      onset of headache and neurologic impairment secondary to an ICH. RESULTS:
      Cerebral angiography showed characteristic findings of diffuse vasculitis. Both
      patients were subjected to biopsy and both failed to reveal evidence of
      vasculitis. CONCLUSION: This report is the first to document the normal
      histologic features of BACNS in the setting of an ICH. Although these
      angiographic changes are similar to vasculitis, these processes can be
      differentiated on clinical grounds, which is of vital importance as the treatment
      and clinical course of BACNS is more benign. Furthermore, the presence of an ICH
      in the setting of vasoconstriction seen on angiography may represent a novel
      feature in some patients with BACNS and is not necessarily a harbinger of the
      more malignant PCNSV.

PMID- 17445627
TI  - Traumatic spinal cord infarction in a child: case report and review of
      literature.
AB  - BACKGROUND: Traumatic spinal cord infarction was initially described in the era
      previous to the availability of MRI. This entity occurs in children and affects
      the thoracic spinal cord, usually presenting as a delayed cord injury. Patients
      have a high incidence of associated blunt thoracic or retroperitoneal trauma and
      arterial hypotension at admission. The described mechanism of injury is a
      traumatic occlusion of the aortic branches nourishing the spinal cord. It shares
      several characteristics with SCIWORA. In past years, the presence of this injury
      has received little importance. CASE DESCRIPTION: A 5-year-old boy suffered from
      high-energy blunt trauma over the thoracoabdominal area, presenting hypotension,
      retroperitoneal injury, and delayed complete thoracic SCI. An MRI showed spinal
      cord infarction located in the territory of AKA. During subsequent examinations,
      the boy did not show signs of neurological improvement. CONCLUSION: It is
      important to include TSCIf in the diagnosis of children who present delayed SCI
      (hours to 4-5 days), especially if the injury is located in the thoracic cord and
      is accompanied by blunt thoracic or abdominal trauma. Because the conventional
      radiographic tests are normal, TSCIf can be considered as a special type of
      SCIWORA.

PMID- 17445628
TI  - Meningioma without dural attachment: case report, classification, and review of
      the literature.
AB  - BACKGROUND: The primary occurrences of meningiomas without attachment to the dura
      are rare. Clinical considerations and pathophysiologic mechanisms about these
      tumors have not been sufficiently explored, and a complete classification has not
      been accomplished. CASE DESCRIPTION: A 16-year-old adolescent boy presented with
      epileptic seizure for 9 years. Neurologic deficits were not found on admission.
      Magnetic resonance imaging revealed a 25 x 23-mm mass lesion without dural
      attachment located in the parietooccipital region. The tumor was iso-intense on
      T1-weighted and hyperintense on T2-weighted images, and became clearly and
      heterogenously enhanced with gadolinium. During surgery, a right parietooccipital
      craniotomy revealed the tumor was completely buried in the sulcus occipitalis
      anterior. Total removal of the tumor was accomplished. Histologic examination
      indicated that the lesion was an atypical meningioma. CONCLUSION: According to
      sites of the tumor, supratentorial meningiomas without dural attachment are
      classified into 5 varieties, and posterior fossa meningiomas without dural
      attachment into 4 categories. Except for intraventricular ones, meningiomas
      without dural attachment predominantly occur in males. The average age is about
      20 years younger than that of meningiomas in general. Fibroblastic meningiomas
      constitute the major subtype. Intraparenchymal or subcortical meningiomas should
      be considered as one type, which may arise from arachnoid cells of the pia mater
      within brain sulcus.

PMID- 17445629
TI  - Cervical radiculopathy secondary to Hodgkin's lymphoma.
AB  - BACKGROUND: Spinal cord/root compression is a rare complication of HL and usually
      seen in the setting of progressive, advanced disease. It is extremely rare to
      occur as an initial presentation of HL. We report a case of HL presented with
      bilateral cervical radiculopathy. METHODS: A case report of a 42-year-old woman
      who presented with C8 cervical radiculopathy and paraspinal mass with extradural
      extension in C7-T1. Biopsy revealed HL. This case report represents a case of HL
      presenting with epidural disease, with nerve root compression as the only
      apparent site of clinical involvement. A review of the literature of patients
      with HL presenting with spinal cord/root compression is presented. RESULT: Our
      patient received chemotherapy and external beam radiation therapy. She achieved
      good recovery of her symptoms and complete response by radiologic criteria. Based
      on a review of the literature, Hodgkin's disease involving the spinal epidural
      space is very responsive to chemoradiotherapy with good prognosis for both
      functional recovery and complete response. CONCLUSION: Chemoradiotherapy is a
      successful treatment for Hodgkin's disease presenting with spinal root
      compression. Surgery should be reserved for urgent decompression, if needed;
      palliation; and maintenance of function and stability.

PMID- 17445630
TI  - Physician power.

PMID- 17445631
TI  - Contralateral pupillary dilatation after intracisternal papaverine instillation.

PMID- 17445632
TI  - Percutaneous nephrolithotomy: variables that influence hemorrhage.
AB  - OBJECTIVES: Renal hemorrhage is one of the most common and worrisome
      complications of percutaneous nephrolithotomy (PCNL). This study attempted to
      identify variables that might influence hemorrhage during PCNL to help urologists
      establish preventative and treatment strategies for bleeding during PCNL
      procedures. METHODS: The data of 193 patients (193 PCNL procedures) were
      retrospectively analyzed. Hemorrhage was estimated by the postoperative decrease
      in hematocrit factored by the quantity of any blood transfusion. Various
      preoperative and operative factors were assessed for their association with blood
      loss using univariate, forward multivariate regression and correlation analysis.
      RESULTS: The mean patient age was 45.7 +/- 14.4 years (range 5 to 74). The
      overall stone-free rate was 85.4%. The average hematocrit decrease was 8.7% +/-
      5.39% (range 0.3 to 24.7). Forward multivariate regression analysis identified
      five significant variables that influenced PCNL-related hemorrhage: stone type (P
      = 0.003), number of tracts (P = 0.010), method of dilation (P = 0.010), diabetes
      (P = 0.022), and stone surface area (P = 0.049). A statistically significant
      difference was found in relation to the occurrence of hemorrhage between patients
      with caliceal stones and partial staghorn stones (P = 0.008) and complete
      staghorn stones (P = 0.006), single tracts and multiple tracts (P = 0.038),
      balloon dilators and Amplatz dilators (P = 0.007), patients with small stones
      (1000 mm2 or smaller) and large stones (greater than 1000 mm2; P = 0.018) on
      univariate analysis. Also, the stone surface area (P = 0.019) and number of
      tracts (P = 0.024) showed a positive correlation with the mean hematocrit
      decrease. CONCLUSIONS: Staghorn stones, multiple tracts, the presence of
      diabetes, and large stones were associated with increased renal hemorrhage during
      PCNL on multivariate analysis. However, balloon dilation was associated with
      decreased hemorrhage.

PMID- 17445633
TI  - Interstitial cystitis and female sexual dysfunction.
AB  - OBJECTIVES: To use the Female Sexual Function Index (FSFI) to compare female
      sexual dysfunction in patients with interstitial cystitis/painful bladder
      syndrome (IC) with that in controls. METHODS: Consecutive patients with IC and
      asymptomatic controls were tested for voiding diary voided volumes, Pelvic Pain
      and Urgency/Frequency Questionnaire scores, and FSFI scores. RESULTS: Of the 97
      subjects, 75 had IC and 22 were controls. The mean age was 38 and 43 years (P =
      0.09), the voided volume was 165 mL and 294 mL (P <0.0001), and the Pelvic Pain
      and Urgency/Frequency Questionnaire score was 18 versus 3 (P <0.0001) for the IC
      and control groups, respectively. The total adjusted FSFI scores differed between
      patients with IC and the controls (20.2 +/- 9.6 versus 29.0 +/- 6.8,
      respectively, P <0.001). Using 26.55 as the cutpoint, 51 patients with IC (68%)
      had an abnormal FSFI score versus 3 controls (14%; P <0.001). Patients with IC
      scored worse on all domains of female sexual dysfunction than did the controls (P
      <0.01). CONCLUSIONS: The results of our study have shown that female patients
      with IC have sexual dysfunction, including pain, more commonly than do controls.

PMID- 17445634
TI  - Treatment of postoperative ileus after bowel surgery with low-dose intravenous
      erythromycin.
AB  - OBJECTIVES: Treatment of postoperative ileus remains unsatisfactory. Erythromycin
      (EM), a macrolide antibiotic, has prokinetic effects on the gut. We investigated
      whether intravenous erythromycin decreases the time to the return of normal bowel
      function after bowel surgery in patients with bladder cancer and interstitial
      cystitis who have undergone cystectomy and urinary diversion. METHODS: We
      conducted a double-blind, randomized, placebo-controlled study of 22 volunteers.
      On the first postoperative day, patients began receiving intravenous erythromycin
      (125 mg) or placebo every 8 hours (maximum of 21 doses). The patients' ability to
      tolerate a general diet and return of bowel function was monitored. RESULTS: A
      general diet was tolerated at a median of 9 days postoperatively for the EM arm
      and 8 for the placebo arm (P = 0.60). The first bowel sounds were detected at an
      average of 2 postoperative days for the EM arm and 3 for the placebo arm (P =
      0.88). First flatus was present an average of 5 days postoperatively for both
      study arms (P = 0.35). The first bowel movement was present an average of 6 days
      postoperatively for the EM arm and 5 for the placebo arm (P = 0.98). CONCLUSIONS:
      No significant difference was found between EM and placebo with regard to the
      onset of bowel sounds, passage of flatus, passage of the first bowel movement,
      and the time to tolerate a general diet. These data indicate that erythromycin is
      not useful in improving postoperative bowel function.

PMID- 17445635
TI  - Complications of scrotal surgery for benign conditions.
AB  - OBJECTIVES: Frequent complications have been reported after scrotal surgery. We
      reviewed our experience to determine the complication rates, risk factors, and
      how our experience might differ from other series. METHODS: We reviewed all
      scrotal surgery for benign conditions at the Veterans Affairs Puget Sound Health
      Care System from 1998 to 2004. The abstracted data included indications,
      comorbidities, perioperative antimicrobial use, operative procedures, use of
      drains, and complications. RESULTS: Ninety-five patients underwent 110
      procedures, including hydrocelectomy (55%), spermatocelectomy (15%),
      epididymectomy (4%), and bilateral or combination procedures (27%). Preoperative
      antimicrobial administration was documented before 80 (73%) of the 110
      procedures. The follow-up ranged from 0 to 85 months (mean 36). Complications
      occurred after 22 (20%) of the 110 procedures and included recurrences (6%),
      hematomas (5%), and infections (3.6%), with 95% of complications occurring after
      hydrocelectomy (odds ratio 9.1, 95% confidence interval 1.1 to 71.6). The
      potential patient and surgical risk factors considered were immunocompromised
      status, undergoing a bilateral procedure, a high American Society of
      Anesthesiologists score, body mass index, and the use of drains. CONCLUSIONS: Our
      overall complication rate was 20%, with most occurring after hydrocele surgery
      (chi-square, P = 0.01). The 3.6% wound infection rate was substantially lower
      than that in recent series in which preoperative antimicrobial agents were not
      prescribed. In the absence of a prospective clinical trial, these findings
      suggest that scrotal procedures might merit consideration of routine
      antimicrobial prophylaxis.

PMID- 17445636
TI  - Do anatomic factors pose a significant risk in the formation of lower pole
      stones?
AB  - OBJECTIVES: To determine whether various anatomic factors predispose to a lower
      pole stone on one side compared with the other. METHODS: We analyzed the
      intravenous urography pictures of 40 consecutive patients presenting with a
      single lower pole stone. Measurements were taken of the infundibulopelvic angle
      (IPA), ureteroinfundibular angle, infundibular width, pelvicaliceal height,
      infundibular length, and pelvicaliceal angle of the affected and normal kidney.
      The IPA was measured according to the methods of Sampaio, Bagley, and Elbahnasy.
      A comparison was made to determine whether any of these measurements predisposed
      one side to form stones. RESULTS: The mean age was 47 years (range 20 to 80). The
      mean stone size was 9.2 mm (range 5 to 20). The mean IPA was 94.82 degrees
      (Sampaio), 56.17 degrees (Bagley), 60.40 degrees (Elbahnasy), and 49.15 degrees
      (Sampaio) on the affected kidney and 95.97 degrees (P = 0.66), 57.47 degrees (P =
      0.57), 65.9 degrees (P = 0.04), and 54 degrees (P = 0.07) on the normal side. A
      statistically significant difference was found only when we measured the IPA as
      described by Elbahnasy. The mean infundibular width was 4.4 mm on both sides (P =
      0.99). The caliceopelvic height was 21.6 mm on the affected side and 22.6 mm on
      the normal side (P = 0.30). The infundibular length was 28.6 mm and 27.4 mm (P =
      0.16) and the caliceopelvic angle was 48 degrees and 47.6 degrees (P = 0.8) on
      the affected and normal kidneys, respectively CONCLUSIONS: Lower pole anatomy as
      a risk factor for stones depends on the type of measurement used. A consensus
      should be reached to define how exactly the IPA should be measured. Other
      anatomic factors were not significantly different between the affected and normal
      side in our study.

PMID- 17445637
TI  - Comparing two local anesthesia techniques for extracorporeal shock wave
      lithotripsy.
AB  - OBJECTIVES: To evaluate the efficacy of a eutectic mixture of local anesthetics
      (EMLA) cream compared with dimethyl sulfoxide (DMSO) with lidocaine during
      extracorporeal shock wave lithotripsy (ESWL) in a prospective randomized study.
      METHODS: Of 167 patients, 85 received 10 g of EMLA cream (EMLA group) and 82
      received 10 g of 40% DMSO (DMSO group) with an amount of lidocaine equal to that
      in the lidocaine gel, applied to the skin of the flank at the area of entry of
      the shock wave marked by the urologist. A second-generation lithotriptor Siemens
      Lithostar was used. The degree of pain was rated by the patients using a 10-point
      visual analog scale. RESULTS: In 80 patients in the EMLA group (94%), the entire
      procedure was performed with no, minor, or tolerable pain after the application
      of EMLA cream (pain score 5.2 +/- 1.3). In 5 EMLA patients (6%), EWSL was
      interrupted because of intolerable pain. Of the 82 DMSO patients, 80 (98%)
      underwent the entire procedure with no, minor, or tolerable pain after the
      application of DMSO with lidocaine (pain score 3.7 +/- 1.1). In 2 DMSO patients
      (2%), EWSL was interrupted because of intolerable pain. The pain scores were
      significantly lower for the DMSO group than for the EMLA group (P = 0.011).
      CONCLUSIONS: Our findings have indicated that the pain scores were significantly
      lower for the DMSO group than for the EMLA group. In addition to the local
      anesthetic effect of DMSO, diuretic, anti-inflammatory, muscle relaxant, and
      hydroxyl radical scavenger effects can be important for patients undergoing ESWL.
      These effects should be evaluated with new studies of patients undergoing ESWL.

PMID- 17445638
TI  - How small can we go? Percutaneous nephrolithotomy using 6F nephroureteral
      catheter.
AB  - OBJECTIVES: To retrospectively examine our percutaneous nephrolithotomy pathway
      to determine the efficacy of a 6F antegrade nephroureteral catheter (NUC).
      METHODS: The records of 99 consecutive patients who underwent percutaneous
      nephrolithotomy from 1998 to 2000 were reviewed. All patients were admitted the
      day before percutaneous nephrolithotomy and underwent placement of a nephrostomy
      tube. The following day, after balloon dilation of the access tract and
      performance of the procedure through a 30F sheath, an internal-external 6F NUC
      was left in place. Nephrostograms were performed on postoperative day 1, and, if
      negative for extravasation or residual stones, the stent was removed. The
      postoperative parameters included the length of stay, intravenous narcotic use,
      complications, and time to removal of the indwelling stent. RESULTS: The average
      procedure time was 103 minutes (range 30 to 300), with a mean stone size of 1.7
      cm. The average length of stay was 2.5 days, with postoperative intravenous
      narcotic use lasting 1.7 days. Of the 99 NUCs placed, 82% were removed by
      postoperative day 2. Eleven patients had either renal (n = 8) or ureteral (n = 3)
      extravasation requiring prolonged stenting, and nine had residual stones
      requiring a second-look procedure. Multivariate analysis demonstrated that
      prolonged narcotic use, days with an indwelling stent, and longer procedure times
      correlated significantly with a longer length of stay (P <0.001). The proportion
      of minor and major complications was 18% and 5%, respectively. CONCLUSIONS: The
      results of our study have indicated that the 6F NUC minimizes postoperative
      intravenous narcotic use and expedites both recovery and discharge. Because it is
      the smallest nephroureteral catheter reported to date for this use, we recommend
      it be incorporated into prospective studies with validated pain questionnaires.

PMID- 17445639
TI  - Comparative evaluation of efficacy of use of tamsulosin and/or tolterodine for
      medical treatment of distal ureteral stones.
AB  - OBJECTIVES: To evaluate the activity of the therapeutic agents (tamsulosin and/or
      tolterodine) used to accelerate the expulsion of stones and to reduce the
      probable complications during observation of the medical treatment of distal
      ureteral stones to allow spontaneous passage. METHODS: A total of 120 patients
      with distal ureteral stones were included in the study. Patients with stones less
      than 10 mm and allowing urinary flow were included in the study. The patients
      were studied in four randomly divided groups. Group 1 patients received
      tamsulosin 0.4 mg/day, group 2 patients received tamsulosin 0.4 mg/day plus
      tolterodine 2 mg (twice a day), group 3 patients received tolterodine 2 mg (twice
      a day), and group 4 patients did not receive any medical treatment (control
      group). RESULTS: Differences among the four groups in patient age and stone
      dimension were not statistically significant (P >0.05). The stone expulsion rates
      were greater (P <0.05) in groups 1 and 2 than in groups 3 and 4. A significant
      variation (P <0.05) regarding the time to stone expulsion was observed in groups
      1 and 2. CONCLUSIONS: In our study, the use of tamsulosin for the expulsion of
      distal ureteral stones was effective; however, the use of tolterodine provided no
      additional advantages.

PMID- 17445640
TI  - Laparoscopic adrenalectomy for suspected metastasis of adrenal glands: our
      experience.
AB  - OBJECTIVES: To present our experience in laparoscopic adrenalectomy for isolated
      adrenal metastasis. METHODS: A total of 34 adrenalectomies were performed in 32
      patients for incidental adrenal masses discovered at primary tumor diagnosis or
      during follow-up. The primary tumors diagnosed were 13 cases of lung carcinoma, 9
      of renal cell carcinoma, 2 of colorectal carcinoma, 2 of bladder carcinoma, and 1
      each of ovarian carcinoma, breast cancer, gastric cancer, and melanoma. Two
      patients had no history of a primary tumor. The mean patient age was 59 years
      (range 26 to 75). The male/female ratio was 1.9:1. RESULTS: The mean operative
      time was 87 minutes (range 40 to 240). The average blood loss was 89 mL (range 0
      to 1000). No conversions to open surgery were needed. The mean hospital stay was
      3 days (range 1 to 5). One intraoperative diaphragmatic lesion developed that was
      repaired laparoscopically, and 1 patient had a pancreatic fistula that was
      managed by percutaneous drainage. The mean tumor size was 4.3 cm (range 1.5 to
      9). The microscopic analysis revealed 22 malign lesions (64.7%) and 12 cases of
      benign pathologic features (35.3%). The mean survival time was 26 months (range 4
      to 64) for the 22 patients with malign lesions. In 2 patients (9.1%), the
      surgical margins were positive. CONCLUSIONS: Laparoscopic adrenalectomy for small
      isolated metastases is feasible. However, because of the high risk of positive
      margins, this procedure should only be done by expert laparoscopists. We did not
      find a correlation between mass size and malignancy. Nevertheless, we believe
      that longer follow-up is mandatory before definitive conclusions can be drawn.

PMID- 17445641
TI  - Superselective embolization as first step of laparoscopic partial nephrectomy.
AB  - OBJECTIVES: Laparoscopic partial nephrectomy is currently very hard to perform
      because of the great difficulty in obtaining renal parenchymal hemostasis during
      tumor excision and the consequent high risk of bleeding. The aim of this study
      was to propose a method to decrease the risk of bleeding, consisting of the
      superselective embolization of tumor vessels before performing the laparoscopic
      partial nephrectomy. METHODS: Fifty patients with small, solitary, enhancing,
      predominantly exophytic renal tumors underwent a superselective radiographically
      guided embolization of tumor vessels. An average of 6 hours after embolization,
      the patients underwent partial laparoscopic nephrectomy, with transperitoneal
      access and three trocars placed, under balanced general anesthesia. The mean
      operative time was measured, as was the mean estimated blood loss. RESULTS: The
      mean operative time was 90 minutes, the mean estimated blood loss was 200 mL, and
      the average hospital stay was 6 days. Complications were reported in only 2
      patients. The final pathologic evaluation confirmed the diagnosis of renal cell
      carcinoma in 43 cases. The median follow-up was 11 months and, to date, the
      examinations have revealed no recurrences in any of the cases. CONCLUSIONS:
      Superselective embolization is a valid option for laparoscopic partial
      nephrectomy. The procedure does not require any regional vascular control or
      clamping, reduces the estimated blood loss, and reduces the operative time.

PMID- 17445644
TI  - Necessity of routine postoperative heparinization in non-risky live-donor renal
      transplantation: results of a prospective randomized trial.
AB  - OBJECTIVES: To determine the exact value of postoperative heparinization in
      preventing thrombotic sequelae in non-risky renal transplants and to assess the
      possible hazards of this therapy through a prospective randomized trial. METHODS:
      Of 120 consecutive live-donor renal transplants, 45 patients were excluded
      because of young age, multiple or atheromatous graft arteries, a history of
      thromboembolic disease, or intraoperative technical difficulties. The remaining
      patients were prospectively randomized into three groups, with 25 patients each.
      Group 1 did not undergo heparinization. Groups 2 and 3 received a prophylactic
      dose of low-molecular-weight heparin and conventional heparin, respectively, for
      1 week. RESULTS: None of our patients in any group developed graft vascular
      thrombosis, deep venous thrombosis, or pulmonary embolism, and the rate of
      spontaneous closure of arteriovenous fistulas was comparable among the three
      groups (P = 0.79). No statistically significant difference was found among the
      three groups in terms of the development of significant perirenal hematomas, rate
      of blood transfusions, or mean number of transfused units (P = 0.37, P = 0.56,
      and P = 0.69, respectively). In contrast, a significant decrease in the
      hemoglobin level occurred in group 3 compared with group 1 among nontransfused
      patients (1.6 +/- 0.8 g% and 0.7 +/- 0.9 g%, respectively; P = 0.01). Moreover, a
      significant shortening of lymph drainage time and a reduction of the total amount
      of lymphorrhea were found in group 1 compared with groups 2 and 3 (P = 0.01, P =
      0.03, respectively). CONCLUSIONS: Postoperative heparinization should not be
      routinely indicated in non-risky live-donor renal transplantation.

PMID- 17445645
TI  - Long-term follow-up of hand-assisted laparoscopic radical nephrectomy for organ
      confined renal cell carcinoma.
AB  - OBJECTIVES: To evaluate the efficacy and long-term outcomes of hand-assisted
      laparoscopic radical nephrectomy (HALRN) in treating clinically localized renal
      cell carcinoma. METHODS: We analyzed the data from 54 patients who underwent hand
      assisted laparoscopic radical nephrectomy (HALRN) and 70 patients who underwent
      conventional open radical nephrectomy (ORN) in our institution from January 1998
      to December 2002 for clinical Stage T1N0M0 or T2N0M0 renal cell carcinoma. The
      data were collected retrospectively by reviewing the medical records. All
      specimens were confirmed by pathologic examination. We compared the surgical
      results and long-term oncologic outcomes between the two groups. RESULTS: The
      median follow-up period in the HALRN group was 44.5 months (range 16 to 73) and
      in the ORN group it was 68 months (range 43 to 93). Patient age, sex, body mass
      index, pathologic parameters, and American Society of Anesthesiologists
      classification were not significantly different between the two groups. The HALRN
      group had a significantly longer operative time (204 minutes versus 181 minutes,
      P = 0.03) and less blood loss (161 mL versus 630 mL, P <0.01). The complication
      rates for the ORN and HALRN groups were similar (10% and 7.4% respectively, P =
      0.62). No conversions to an open procedure or intraoperative mortality occurred
      in the HALRN group. The average hospital stay, length of wound, and parenteral
      narcotic analgesic dose were significantly less in the HALRN group. The 5-year
      disease-free rate and disease-specific survival rate were comparable in the two
      groups. CONCLUSIONS: The results of our study have shown that HALRN is a less
      invasive technique with 5-year disease-free and disease-specific survival rates
      comparable to those after ORN in treating patients with clinically localized
      renal cell carcinoma.

PMID- 17445646
TI  - Oncologic control after open or laparoscopic nephroureterectomy for upper urinary
      tract transitional cell carcinoma: a single center experience.
AB  - OBJECTIVES: To determine the surgical and oncologic outcomes in patients who
      underwent either open nephroureterectomy (ONU) or laparoscopic nephroureterectomy
      (LNU) for upper urinary tract transitional cell carcinoma. METHODS: We performed
      a retrospective review of data for patients who underwent ONU or LNU for upper
      urinary tract transitional cell carcinoma from 1994 to 2004 at one institution.
      The recorded data included sex, age, mode of diagnosis, smoking, history of
      bladder cancer, type of surgery, complications, tumor site, tumor size, tumor
      stage, tumor grade, length of hospital stay, recurrence, and progression. We also
      determined the recurrence and survival rates. RESULTS: We reviewed the data for
      46 patients. The median age was 70 years. Seven patients had a history of bladder
      cancer. Overall, 26 patients underwent ONU and 20 LNU. No differences in the
      complication rate (15% versus 15%) were observed. The median hospital stay was 4
      days (range 3 to 6) after LNU and 9 (range 7 to 12) after ONU (P <0.001). The
      tumor stage and grade were independent prognostic factors for survival on
      multivariate analysis (P <0.05). The 5-year disease-specific survival rate was
      89.4% for low-grade tumors and 63.1% for high-grade tumors (P = 0.04). ONU was
      associated with high-grade (P = 0.02) or invasive (P = 0.001) tumors. The 5-year
      tumor-free survival rate after ONU and LNU was 51.2% and 71.6%, respectively (P =
      0.59). CONCLUSIONS: LNU does not affect the mid-term oncologic control and
      enables a shorter hospital stay. It can be recommended as an alternative to ONU
      in the management of low-risk upper urinary tract transitional cell carcinoma
      (Stage T1-T2 and/or low-grade disease). However, long-term follow-up is necessary
      to recommend it for highly invasive tumors (Stage T3-T4 or N+).

PMID- 17445647
TI  - Laparoscopic radical nephrectomy for renal carcinoma with known level I renal
      vein tumor thrombus.
AB  - OBJECTIVES: Laparoscopic nephrectomy in patients with known venous involvement is
      an emerging technique. The goal of this study was to describe our experience and
      outcomes with laparoscopic nephrectomy for patients with preoperatively diagnosed
      level I (renal vein) tumor thrombus. METHODS: The data from all patients
      undergoing laparoscopic nephrectomy by one surgeon from July 1, 2004 to February
      28, 2006 were reviewed. The patients with a preoperatively diagnosed tumor
      thrombus were included in the study. A pure laparoscopic transperitoneal
      technique was used with intraoperative ultrasonography to ensure complete removal
      of the thrombus. The medical records were reviewed for clinical, operative, and
      follow-up information. RESULTS: Five patients were identified. The mean age,
      American Society of Anesthesiologists score, and tumor size were 59.8 years
      (range 34 to 81), 2.6 (range 2 to 3), and 5.5 cm (range 4 to 6), respectively.
      The mean operative time and estimated blood loss were 119.6 minutes (range 92 to
      180) and 150 mL (range 50 to 300), respectively. The mean hospital stay was 3.6
      days (range 2 to 4), and no complications occurred. The final stage was T3b with
      negative margins in all cases. The mean Fuhrman grade was 2.4 (range 2 to 3). Two
      patients had known metastases and underwent cytoreductive nephrectomy. These 2
      patients were alive at a mean follow-up of 11.5 months. Of the other 3 patients,
      at a mean follow-up of 8.7 months, 2 had no evidence of disease, and 1 had
      developed recurrence in the liver and was treated with sorafenib, resulting in
      tumor regression. CONCLUSIONS: Pure laparoscopic transperitoneal nephrectomy for
      patients with preoperatively diagnosed level I tumor thrombus is safe and
      effective in experienced hands. Additional series are needed to examine the long
      term oncologic outcomes.

PMID- 17445648
TI  - Deceased-donor kidney transplantation in prune belly syndrome.
AB  - OBJECTIVES: To present the long-term outcome of deceased-donor kidney
      transplantation in prune belly syndrome (PBS). All the PBS transplant patients
      had undergone extensive pretransplant urologic tract preparation. We also
      compared the patient and graft survival in an age-matched control group who
      underwent transplantation for end-stage renal disease due to a nonposterior
      urethral valve in our urology department. METHODS: From 1988 to 2003, 11 kidneys
      were transplanted in 8 male patients with PBS. The mean age was 13.5 years (range
      4 to 32). Patient and graft survival were assessed and compared with that of a
      group of 103 deceased-donor kidney transplantations performed in 86 age-matched
      controls who underwent transplantation because of end-stage renal disease due a
      nonposterior urethral valve (mean age 13.9 years, range 1.7 to 20). RESULTS: In
      the PBS group, a total of 23 pretransplant urologic procedures were performed.
      One operation was performed in 1 patient, two in 2, three in 2, and four in 3
      patients. In the PBS group, after transplantation, adequate bladder function was
      maintained by intermittent catheterization in 4 patients and timed voiding in 3;
      1 patient had undergone pretransplant ileal conduit formation. Up to 10 years
      after transplantation, we found no difference in patient and graft survival
      between the two groups (P = 0.466 and P = 0.838, respectively). CONCLUSIONS:
      Aggressive pretransplant urologic tract preparation and keeping the postvoid
      residual urine volume to a minimum are needed in patients with PBS. With such
      management, the outcome of kidney transplantation in our patients with PBS was
      not different from that of other patients who underwent transplantation for other
      causes of end-stage renal disease in our department.

PMID- 17445649
TI  - Microvascular tumor invasion: prognostic significance in low-stage renal cell
      carcinoma.
AB  - OBJECTIVES: To evaluate the role of microvascular tumor invasion (MVI) in
      clinical behavior and prognosis of low-stage renal cell carcinoma. METHODS: We
      retrospectively reviewed the records of patients who had undergone radical
      nephrectomy from 1990 to 2004 for clinically confined kidney tumors (Stage T1
      T2N0M0) with a minimal follow-up period of 1 year. The pathology slides were
      reviewed regarding tumor diameter, pathologic tumor stage, histologic cell type,
      nuclear grade, macroscopic or MVI, perirenal fat invasion, and neoplastic lymph
      node involvement. RESULTS: A total of 48 patients, 22 men and 26 women (mean +/-
      SD age 50.73 +/- 13.03 years, range 20-80) were included in the study. The
      patients were followed up for a mean +/- SD of 37.65 +/- 18.19 months (range 12
      60). MVI was encountered in 8 patients (16.7%); 50% developed treatment failure
      in the form of distant metastases. Of the 40 patients without MVI, only 2 (5%)
      had treatment failure. MVI had a statistically significant association with sex
      (P = 0.017) and stage (P = 0.039). On comparing treatment failure with different
      patient and histologic parameters, a statistically significant association was
      noted with sex (P = 0.006) and MVI (P = 0.005). The 5-year disease-free survival
      rate was estimated at 45% and 90% when MVI was and was not present. Only MVI
      showed an independent statistically significant impact (P = 0.007) on
      multivariate analysis considering the impact of MVI, stage, grade, cell type,
      perirenal fat invasion, tumor size, and patient age on disease-free survival.
      CONCLUSIONS: The results of our study have shown that MVI is an independent and
      relevant prognostic parameter for clinically low-stage renal cell carcinoma.

PMID- 17445650
TI  - Clinically relevant reduction in risk of recurrence of superficial bladder cancer
      using 5-aminolevulinic acid-induced fluorescence diagnosis: 8-year results of
      prospective randomized study.
AB  - OBJECTIVES: Several studies have shown that 5-aminolevulinic acid (5-ALA)-induced
      fluorescence cystoscopy improves the detection of superficial bladder cancer. The
      results have suggested a reduced rate of recurrent tumors with the use of 5-ALA
      fluorescence before bladder tumor resection. We performed a prospective,
      randomized trial to investigate whether the long-term tumor recurrence and
      residual tumor rates can be decreased using 5-ALA fluorescence diagnosis (FD).
      METHODS: A total of 301 patients with suspected superficial bladder carcinoma
      were randomized to transurethral resection (TUR) using conventional white light
      (WL) or FD. TUR was repeated to evaluate the residual tumor rate. In addition,
      patients were followed up for a median of 83 (WL) and 86 (FD) months to evaluate
      recurrence-free survival (RFS). RESULTS: Of the 301 patients, 191 were available
      for the efficacy analysis. The residual tumor rate was 25.2% in the WL arm versus
      4.5% in the FD arm (P <0.0001). The RFS rate after 2, 4, 6, and 8 years was 73%,
      64%, 54%, and 45% in the WL group and 88%, 84%, 79%, and 71% in the FD group,
      respectively, revealing a statistically significant difference in favor of
      fluorescent TUR (P = 0.0003). CONCLUSIONS: 5-ALA-induced FD is significantly
      superior statistically to conventional WL TUR with respect to the residual tumor
      rate and RFS. This advantage of decreased bladder tumor recurrence risk was
      maintained with high statistical significance for at least 8 years. The
      differences in RFS imply that FD offers a clinically relevant procedure to reduce
      the incidence of tumor recurrence.

PMID- 17445651
TI  - Obesity and benign prostatic enlargement: a large observational study in China.
AB  - OBJECTIVES: To investigate the associations of prostate enlargement with obesity
      and hypertension in Chinese men. METHODS: A total of 649 men from Zhejiang, China
      were invited to the Family Planning Station of Wenlin to undergo prostate volume
      measurement with transrectal ultrasonography. Benign prostatic enlargement (BPE)
      has been defined as a prostate volume larger than 20 cm3. The associations
      between BPE and prostate volume with body mass index (BMI) and blood pressure
      were evaluated by multivariate linear and logistic regression analyses. RESULTS:
      Overweight (BMI of 25 or more but less than 28 kg/m2) and obese (BMI of 28 kg/m2
      or more) men experienced a significantly increased age-adjusted risk of BPE
      compared with men with a lower BMI (odds ratio 1.63, 95% confidence interval 1.16
      to 2.30, and odds ratio 2.26, 95% confidence interval 1.11 to 4.59,
      respectively). Each 0.37-kg/m2 increase (95% confidence interval 0.18 to 0.57, P
      <0.01) in the BMI was associated with a 1-cm3 increase in prostate volume. No
      associations were observed between hypertension and BPE. CONCLUSIONS: This is the
      first study to provide evidence that the BMI is positively associated with
      prostate volume in the Chinese population. Obese Chinese men are at increased
      risk of an enlarged prostate compared with nonobese Chinese men.

PMID- 17445652
TI  - Lower urinary tract symptoms and uroflowmetry in women with type 2 diabetes
      mellitus with and without bladder dysfunction.
AB  - OBJECTIVES: To study the presence of lower urinary tract symptoms and parameters
      of uroflowmetry in women with type 2 diabetes mellitus with and without bladder
      dysfunction versus healthy controls. METHODS: After eliminating the possible
      confounders that might cause bladder dysfunction, 182 female patients at a
      diabetic clinic were evaluated by the American Urological Association Symptom
      Index (AUA-SI) questionnaire and uroflowmetry with postvoid residual (PVR) urine
      volume estimate. Their data were compared with the data from 197 healthy women,
      frequency-matched by age. RESULTS: Using a cutoff value of bladder voiding
      efficiency of less than 75% with a PVR greater than 50 mL but less than 100 mL, a
      PVR greater than 100 mL, or a total volume greater than 500 mL, 47 patients
      (25.8%) were stratified as having bladder dysfunction. These patients had a
      significantly greater mean AUA-SI score (mean +/- standard error of the mean 9.6
      +/- 0.8, P <0.001), as well as a lower maximum uroflow value (15.2 +/- 1.2 mL/s,
      P <0.001) compared with the control groups. The odds ratio of each lower urinary
      tract symptom was significantly greater in this group, except for straining (P =
      0.12). A high proportion with an intermittent uroflow pattern (odds ratio 4.42, P
      <0.001) was also noted. Compared with the healthy controls, the diabetic women
      had no bladder dysfunction and seemed unaffected by the lower urinary tract
      symptoms as defined by the AUA-SI scoring system, with the exception of nocturia
      (odds ratio 2.62, P = 0.006). CONCLUSIONS: Women with diabetes may have an
      increased risk of nocturia even without bladder dysfunction. A high AUA-SI score
      and lower maximum uroflow are likely to be good markers for diabetic bladder
      dysfunction.

PMID- 17445653
TI  - Association between urogenital symptoms and depression in community-dwelling
      women aged 20 to 70 years.
AB  - OBJECTIVES: To determine the association between urogenital symptoms and the
      occurrence of depressive symptoms. METHODS: A random sample of 3200 community
      dwelling women, aged 20 to 70 years, was invited to answer a questionnaire. A
      total of 2042 questionnaires (63.8%) were returned. Urogenital symptoms were
      assessed with the Urogenital Distress Inventory and depressive symptoms with the
      Center for Epidemiological Studies Depression scale. A cutoff value of 16 or more
      on the Center for Epidemiological Studies Depression scale was considered as
      possible clinical depression. Univariate and multivariate logistic regression
      statistics were used. RESULTS: The prevalence of depressive symptoms (Center for
      Epidemiological Studies Depression scale score of 16 or more) was significantly
      greater in women with urinary incontinence than in those without (odds ratio 1.9,
      95% confidence interval 1.6 to 2.3). However, this statistically significant
      association existed for all urogenital symptoms when assessed individually. After
      multivariate adjustment, the statistical significant association with depressive
      symptoms was lost for most urogenital symptoms. Only nocturia remained
      significantly associated with depression throughout all analyses (odds ratio 1.4,
      95% confidence interval 1.1 to 1.8 for the symptom itself; and odds ratio 2.0,
      95% confidence interval 1.3 to 3.2, when considering only bothersome nocturia
      symptoms). CONCLUSIONS: After adjusting for the influence of coexisting
      urogenital symptoms, no association between urinary incontinence and depression
      could be demonstrated. Only nocturia remained significantly associated with
      depressive symptoms.

PMID- 17445654
TI  - Lack of disparity in lower urinary tract symptom severity between community
      dwelling non-Hispanic white, Mexican-American, and African-American men.
AB  - OBJECTIVES: To determine whether disparities exist in the reporting of lower
      urinary tract symptoms (LUTS) in non-Hispanic white (NHW), Mexican-American (MA),
      and African-American (AA) men. METHODS: Data were collected from a prospective,
      community-based cohort assembled to study risk factors associated with prostate
      cancer. Measures included demographics, prostate-specific antigen (PSA), body
      mass index (BMI), and family history of prostate cancer. Lower urinary tract
      symptom severity was assessed in 2804 men (1485 NHW, 964 MA, 355 AA) without
      prostate cancer according to the American Urological Association Symptom Index.
      RESULTS: No significant difference (P = 0.998) was seen in the prevalence of
      moderate or severe LUTS in NHW (34%), MA (34%), and AA (33%) men. No differences
      were found in either obstructive or irritative symptoms among the three groups.
      Age, PSA level, BMI, and family history did not affect symptom severity.
      CONCLUSIONS: Rates of moderate to severe LUTS symptoms in this cohort were
      similar to those in other community-based populations of NHW men. Lower rates of
      moderate or severe symptoms were noted in AA men than previously reported.
      Mexican-American men had similar degrees of LUTS as the general population, and
      with their increased risk for diabetes and renal disease, in-depth study of this
      population is warranted.

PMID- 17445655
TI  - Transobturator tape for treatment of female stress urinary incontinence:
      objective and subjective results after a mean follow-up of two years.
AB  - OBJECTIVES: To verify the objective and subjective outcomes of transobturator
      tape (TOT) in the treatment of female stress urinary incontinence due to urethral
      hypermobility. METHODS: A total of 108 consecutive patients with stress urinary
      incontinence (mean age 58 +/- 4.5 years), who underwent the TOT procedure (43
      patients received the ObTape, 55 patients the Monarc, and 10 patients the I-STOP
      sling) from June 2002 to December 2004, were assessed in December 2005. Before
      surgery, the patients were evaluated by history, physical examination, stress
      test, cotton swab test (Q-Tip test), and ultrasonography. After surgery, the
      compilation of a specific quality-of-life questionnaire was also included. Of the
      108 patients, 35 had previously undergone urogynecologic surgery; associated
      prolapse was repaired simultaneously in 45 patients. The outcomes were analyzed
      considering five postoperative aspects: obstructive symptoms, irritative
      symptoms, urinary continence, pain, and satisfaction. RESULTS: Postoperatively,
      74% reported minimal obstructive symptoms, 78.7% had no urge symptoms, and de
      novo urgency occurred in 14.8%. Objective continence rates were increased
      significantly (80%), although the subjective rate was significantly greater
      (92%). Also, 88% of patients reported no pelvic pain, and only 7.3% reported
      dyspareunia; 88% of patients were significantly satisfied with the TOT procedure.
      Regarding complications, vaginal erosions were reported, using the ObTape, in
      6.4% of patients, sling rejection in 3.8%, and incorrect positioning or sliding
      of the sling in 6.4%. Morbidity did not seem to be affected by previous or
      associated surgery. CONCLUSIONS: The TOT procedure is a simple, safe, and
      effective technique for the treatment of stress urinary incontinence due to
      urethral hypermobility. Our data have demonstrated good global success with a low
      rate of minor complications.

PMID- 17445656
TI  - Serum sex steroid hormones and lower urinary tract symptoms in Third National
      Health and Nutrition Examination Survey (NHANES III).
AB  - OBJECTIVES: To evaluate the association of circulating sex steroid hormones and
      sex hormone binding globulin (SHBG) with lower urinary tract symptoms (LUTS).
      METHODS: We included 260 men, 60 years old or older, who participated in Phase 1
      (1988 to 1991) of the Third National Health and Nutrition Examination Survey and
      for whom surplus serum was available. We measured the serum concentrations of
      testosterone, androstanediol glucuronide (AAG), estradiol, and SHBG. Free
      testosterone was calculated from the circulating testosterone, SHBG, and albumin.
      The cases (n = 128) were men with two to four symptoms (nocturia, hesitancy,
      incomplete emptying, and weak stream), but who had never undergone noncancer
      prostate surgery. The controls (n = 132) were men who neither had symptoms nor
      had undergone noncancer prostate surgery. We adjusted for age, race/ethnicity,
      waist circumference, cigarette smoking, alcohol consumption, and physical
      activity in logistic regression models and used sampling weights. RESULTS: The
      cases had statistically significantly greater AAG and estradiol concentrations
      than did the controls. After multivariate adjustment, the men in the top tertile
      of AAG (odds ratio 2.62, 95% confidence interval 1.12 to 6.14) had a greater risk
      of LUTS compared with men in the bottom two tertiles. Also, men with a greater
      estradiol concentration (odds ratio 1.78, 95% confidence interval 0.91 to 3.49)
      and a greater estradiol/SHBG molar ratio (odds ratio 2.41, 95% confidence
      interval 1.39 to 4.17) had a greater risk of LUTS than did men with lower
      concentrations. No consistent associations were seen for circulating
      testosterone, free testosterone, or SHBG. CONCLUSIONS: In this cross-sectional
      study representative of older U.S. men, circulating AAG, a metabolite of
      dihydrotestosterone, and estradiol were associated with an increased risk of
      having LUTS.

PMID- 17445657
TI  - EPCA-2: a highly specific serum marker for prostate cancer.
AB  - OBJECTIVES: To describe the initial assessment of early prostate cancer antigen
      (EPCA)-2 as a serum marker for the detection of prostate cancer and to examine
      its sensitivity and specificity. METHODS: Serum samples were obtained from 385
      men: those with prostate-specific antigen (PSA) levels less than 2.5 ng/mL, PSA
      levels of 2.5 ng/mL or greater with negative biopsy findings, benign prostatic
      hyperplasia, organ-confined prostate cancer, non-organ-confined disease, and
      prostate cancer with PSA levels less than 2.5 ng/mL. In addition, a diverse group
      of controls was assessed with an enzyme-linked immunosorbent assay to detect an
      epitope of the EPCA-2 protein, EPCA-2.22. RESULTS: Using a cutoff of 30 ng/mL,
      the EPCA-2.22 assay had a 92% specificity (95% confidence interval 85% to 96%)
      for healthy men and men with benign prostatic hyperplasia and 94% sensitivity
      (95% confidence interval [CI] 93% to 99%) for overall prostate cancer. The
      specificity for PSA in these selected groups of patients was 65% (95% CI 55% to
      75%). Additionally, EPCA-2.22 was highly accurate in differentiating between
      localized and extracapsular disease (area under the curve 0.89, 95% CI 0.82 to
      0.97, P <0.0001) in contrast to PSA (area under the curve 0.62, 95% CI 0.50 to
      0.75, P = 0.05). CONCLUSIONS: The results of our study have shown that EPCA-2 is
      a novel biomarker associated with prostate cancer that has high sensitivity and
      specificity and accurately differentiates between men with organ-confined and non
      organ-confined disease.

PMID- 17445658
TI  - Smoking and risk of fatal prostate cancer in a prospective U.S. study.
AB  - OBJECTIVES: To examine the association of cigarette smoking with subsequent fatal
      prostate cancer. METHODS: Two private censuses were conducted in Washington
      County, Maryland, in which 26,810 adult men in 1963 and 28,292 in 1975 provided
      smoking information. Prostate cancer deaths through 2000 (1963 cohort, 240
      deaths; and 1975 cohort, 184 deaths) were ascertained by review of the death
      certificates. Poisson regression analysis was used to estimate the rate ratio of
      prostate cancer death adjusted for age. RESULTS: Overall, cigarette smokers in
      the 1963 census cohort were not more likely to die of prostate cancer than those
      who had never smoked cigarettes, pipes, or cigars when considering the total
      follow-up period. However, current smokers of 20 or more cigarettes per day (rate
      ratio 2.38; 95% confidence interval 0.94 to 5.99) and former smokers (rate ratio
      2.75; 95% confidence interval 1.13 to 6.74) had a greater risk of death from
      prostate cancer during the first 10 years of follow-up. Weaker positive
      associations of prostate cancer death with current and former cigarette smoking
      were seen during the first 10 years of follow-up in the 1975 census cohort.
      Current cigarette smoking at baseline was not associated with the prostate cancer
      incidence. CONCLUSIONS: The lack of an association between cigarette smoking and
      prostate cancer incidence, but the tendency of greater prostate cancer mortality
      in former and current cigarette smokers earlier in the follow-up period is
      consistent with other studies in which smoking was assessed once at baseline.

PMID- 17445659
TI  - Anatomic restoration technique of continence mechanism and preservation of
      puboprostatic collar: a novel modification to achieve early urinary continence in
      men undergoing robotic prostatectomy.
AB  - OBJECTIVES: The puboprostatic ligaments, puboperinealis muscle, and arcus
      tendineus are all recognized as important for continence in men and women. This
      complex of ligaments, muscles, and tendineus aponeurosis acts in unison to
      provide continence and can be disrupted during robotic prostatectomy. We propose
      that preservation of the puboprostatic collar during robotic surgery will help to
      restore early continence in men undergoing robotic prostatectomy. METHODS: We
      performed cadaveric studies in 10 fresh cadavers to devise strategies to leave
      intact the puboprostatic ligaments, muscular collar, and arcus tendineus
      supporting the continence mechanism. We developed reconstructive strategies to
      reconnect the ligaments to the urethrovesical anastomosis, reapproximated the
      muscles, and fixed the distal bladder to the arcus tendineus. These modifications
      were then attempted in 50 consecutive patients who underwent robotic
      prostatectomy for clinically localized prostate cancer. The patient-reported
      outcomes were then used to assess the efficacy of this procedure. RESULTS: The
      technique was reproducible, and the average additional time taken for the final
      reconstruction was only 2 to 5 minutes. The continence rate was 29% in the first
      week, 62% at 6 weeks, 88% at 12 weeks, and 95% in 16 weeks after catheter
      removal. No other differences were found in the operative, oncologic, or
      perioperative outcomes. CONCLUSIONS: This modification helped in the early return
      of continence. It is unlikely that the long-term results will be any different,
      but shortening the recovery time will have psychological, financial, and health
      related quality-of-life benefits for the patients.

PMID- 17445660
TI  - Optimal timing, cutoff, and method of calculation of preoperative prostate
      specific antigen velocity to predict relapse after prostatectomy: a report from
      SEARCH.
AB  - OBJECTIVES: Preoperative prostate-specific antigen (PSA) velocity (PSAV), the
      rate of PSA rise preceding diagnosis, predicts for relapse and cancer death after
      prostatectomy or radiotherapy. We studied the timing, cutoff levels, and method
      of calculation to better define its usefulness. METHODS: The rates of biochemical
      relapse were examined in 471 patients who underwent radical prostatectomy (RP)
      with previous PSA history available. PSAV was calculated by two methods, as the
      difference between two PSAs divided by time, or as the slope of all available
      PSAs within that interval. Kaplan-Meier relapse-free survival was compared among
      the groups with various intervals and cutoff levels in their preoperative PSAV
      definition. Univariate and multivariate analysis examined all preoperative
      factors and PSAV for their association with relapse. RESULTS: The two methods of
      PSAV calculation yielded values within 5% of each other (R2 = 0.91). A PSA
      history that precedes RP by at least 12 months is necessary. A PSAV cutoff level
      of 2 ng/mL/yr or less versus greater than 2 ng/mL/yr appeared optimal for a PSA
      interval spanning 12 to 24 months before RP (P = 0.008). PSAV using a longer
      interval (24 to 36 months) before RP appeared more sensitive, with a cutoff of 1
      ng/mL/yr or less versus greater than 1 ng/mL/yr (P = 0.029) and 2 ng/mL/yr or
      less versus greater than 2 ng/mL/yr (P = 0.0041) associated with relapse. A
      preoperative PSAV of 2 ng/mL/yr or less versus greater than 2 ng/mL/yr was an
      independent factor associated with the risk of relapse after RP. CONCLUSIONS: The
      results of our study have shown that preoperative PSAV is independently
      associated with relapse after RP. However, a minimum interval of 12 months before
      RP is needed, and a PSAV cutoff level of 2 ng/mL/yr appears optimal. A simple two
      point method of calculating PSAV is reliable.

PMID- 17445661
TI  - Additional sampling of dorsal apex on systematic prostate biopsy: impact on early
      detection of prostate cancer.
AB  - OBJECTIVES: To evaluate the significance of additional routine biopsies targeting
      the dorsal apex (DA) in men undergoing transrectal ultrasound (TRUS)-guided
      biopsies. METHODS: This study included 429 patients undergoing TRUS-guided biopsy
      of the prostate. As a rule, 12 cores were taken from each patient, with 8 cores
      taken from the peripheral zones, 2 cores from the transition zones, and 2
      additional cores from the DA. RESULTS: Cancer was detected in 150 patients, of
      whom 97 had positive cores in the DA. Furthermore, cancer was detected only in
      the DA in 14 patients; that is, the increase in the cancer detection rate by
      additional sampling from the DA was 9.3%. Significant differences were found in
      the prostate-specific antigen level, prostate-specific antigen density, digital
      rectal examination findings, TRUS findings, clinical T stage, and percentage of
      positive biopsy cores among the 14 men with positive cores in the DA alone (group
      1), 83 in the DA and other regions (group 2), and 53 in regions except for the DA
      (group 3). Of these, radical prostatectomy was performed in 6, 41, and 26 in
      groups 1, 2, and 3, respectively. No significant differences were found in the
      several pathologic factors among these groups, and 5 of the 6 patients in group 1
      had a tumor volume greater than 0.5 cm3. CONCLUSIONS: Additional sampling of
      biopsy cores from the DA significantly improved the cancer detection rate,
      particularly for early disease; however, this method does not appear to increase
      the detection of insignificant cancer. Accordingly, we recommend performing
      systematic biopsy routinely targeting the DA.

PMID- 17445662
TI  - Comparison of prevalence between self-reported erectile dysfunction and erectile
      dysfunction as defined by five-item International Index of Erectile Function in
      Taiwanese men older than 40 years.
AB  - OBJECTIVES: To conduct a cohort study in men older than 40 years in Taiwan to
      evaluate the prevalence of erectile dysfunction (ED) by self-report and the use
      of the abridged, five-item version of the International Index of Erectile
      Function (IIEF-5). METHODS: From July to August 2003, 990 Taiwanese men older
      than 40 years of age completed a telephone survey designed to assess ED
      prevalence and sexual functioning. ED was identified through respondent self
      report and investigator assessment using the IIEF-5 instrument. Data were
      analyzed using the analysis of variance test, t test, and chi-square test, with
      Yates' correction or Fisher's method. RESULTS: The prevalence of self-reported ED
      was 13.1%, with 26.2% of this subgroup subsequently deemed to not have ED by IIEF
      5 assessment. Among the subgroup of men self-reported to not have ED, 18.8% were
      found to have ED by IIEF-5 assessment. In total, 26.0% of respondents had ED by
      IIEF-5 assessment. The ED prevalence increased with age and a history of chronic
      illness. The frequency of sexual contact and sexual satisfaction were also
      reduced in the respondents with ED. CONCLUSIONS: The prevalence of self-reported
      ED in Taiwanese men older than 40 years of age was 13.1% compared with 26.0%
      using the IIEF-5 assessment. Estimates of ED prevalence in the general population
      should not rely on self-reporting alone because it is likely to underestimate the
      true prevalence of ED.

PMID- 17445663
TI  - Health behaviors and depressive symptoms in testicular cancer survivors.
AB  - OBJECTIVES: Testicular cancer has one of the highest 5-year survival rates of all
      cancer sites. The survival period is marked by an increased risk of secondary
      cancer and cardiovascular events owing to treatment-related toxicities. The
      purposes of this cross-sectional study were to determine the prevalence of health
      behaviors and depressive symptoms and to assess the relationship between
      depression and health behaviors in survivors of testicular cancer. METHODS: A
      total of 162 survivors of testicular cancer 2 to 10 years after their diagnosis
      completed a one-time telephone interview. The interview included a battery of
      questions from the Behavioral Risk Factor Surveillance System assessing health
      behaviors (smoking, physical activity, cholesterol screening, colorectal cancer
      screening, alcohol consumption, and fruit and vegetable intake) and the Centers
      for Epidemiological Studies-Depression (CES-D) questionnaire assessing depressive
      symptoms. RESULTS: The interviews revealed a low prevalence of positive health
      behaviors among survivors of testicular cancer. The percentage (17.5%) of
      survivors of testicular cancer who scored above the cutoff on the CES-D was
      greater than that (11%) of large-scale population-based estimates in men aged 19
      to 44 years. Smoking was significantly related to depression. Depressive symptoms
      (CES-D score) differed significantly depending on smoking status (current
      smokers, mean = 15.2; former smokers, mean = 6.2, P <0.001; and never smokers,
      mean = 8.7, P <0.001). CONCLUSIONS: Given the increased risk of cancer and
      treatment-related morbidities of these survivors, the findings of this study
      suggest that healthcare professionals should encourage survivors of testicular
      cancer to engage in positive health behaviors and check for depressive symptoms.

PMID- 17445664
TI  - Hypogonadism and androgen deficiency symptoms in testicular cancer survivors.
AB  - OBJECTIVES: To investigate the prevalence of hypogonadism in correlation with
      androgen deficiency symptoms in testicular cancer survivors. METHODS: Luteinizing
      hormone, follicle-stimulating hormone, serum testosterone,
      dehydroepiandrosterone, and sex hormone binding globulin levels were determined
      in patients who had undergone treatment for unilateral testicular cancer.
      Patients with serum testosterone levels less than 3.0 ng/mL were classified as
      hypogonadal; all other testosterone levels signified eugonadism. Additionally,
      all patients completed the Aging Males' Symptoms scale: scores of less than 26
      indicated no androgen deficiency symptoms and scores greater than 27 indicated
      symptoms. RESULTS: According to testosterone level, 18 (26.5%) of 68 patients
      were hypogonadal and 50 (73.5%) were eugonadal (P = 0.456). According to the
      Aging Males' Symptoms scale, 23 (33.8%) of the 68 patients had androgen
      deficiency symptoms and 45 (66.2%) had no symptoms (P = 0.267). The median
      testosterone level was 3.6 ng/mL in all patients with androgen deficiency
      symptoms, 2.4 ng/mL in patients with androgen deficiency symptoms who were
      hypogonadal, and 4.7 ng/mL in those with androgen deficiency symptoms who were
      eugonadal. CONCLUSIONS: Testicular cancer survivors are at risk of developing
      hypogonadism and androgen deficiency symptoms. However, no specific testosterone
      threshold could be detected at which symptoms start, indicating that each patient
      has an individual testosterone threshold for androgen deficiency symptoms.

PMID- 17445665
TI  - Long-term follow-up after laser therapy for penile carcinoma.
AB  - OBJECTIVES: Although in many cases of penile carcinoma, laser therapy has become
      the standard treatment, opinion still differs regarding the risks related to the
      relatively high rate of recurrence that accompanies this form of treatment. In
      this study, we reviewed the results of neodymium:yttrium-aluminum-garnet laser
      treatment of 44 consecutive patients with penile carcinoma in our institution
      from 1986 to 2003. METHODS: We created five groups, on the basis of the T stage
      and grade of the tumor. Of the 44 patients, 21 had Stage T1, 17 had Stage T2, and
      6 had carcinoma in situ. RESULTS: Local disease recurrence (in the treated area)
      occurred in 48% of the treated patients, and in 20% of the patients, the first
      recurrence was elsewhere on the glans penis. These were subsequently treated by
      laser therapy or partial amputation. In 10 cases, nodal metastases were found.
      Eight of these cases were Stage T2. Our results suggest a stronger prognostic
      role for the primary T stage of the tumor than for the tumor grade, with respect
      to the risk of nodal metastasis. CONCLUSIONS: From the high recurrence rate in
      our series, we decided to perform a wider initial laser excision and to diminish
      the number of retreatments to less than three. We also now believe that laser
      therapy is best for Stage Tis and T1 tumors exclusively. Only selected patients
      with T2 tumors should be treated in combination with early lymph node resection.

PMID- 17445666
TI  - Bladder wall thickness in healthy school-aged children.
AB  - OBJECTIVES: To evaluate the effectiveness of transabdominal ultrasonography for
      bladder volume and detrusor muscle thickness and to research the relationship of
      these measurements with age, height, and body mass index. METHODS: We reviewed
      the records of 244 healthy, school-aged children from February to May 2003. After
      a complete urologic examination, the weight and height of all children were
      measured, and their body mass index was determined. Transabdominal
      ultrasonography with a high-frequency probe was performed to obtain the anterior,
      posterior, and lateral bladder wall thicknesses. RESULTS: The mean age of the
      children was 10.7 +/- 3.6 years (range 7 to 15), and the mean bladder volume was
      256 cm3 (range 78 to 790). The relationship between bladder volume and age was
      significant (P = 0.0001, r = 0.568). The mean anterior, posterior, and lateral
      detrusor thickness was 1.42 mm (range 0.8 to 2.8), 1.57 mm (range 0.7 to 3.1),
      and 1.49 mm (range 0.6 to 2.6), respectively. The relationships between
      increasing age and the anterior and posterior wall thicknesses were significant
      (P <0.05), but the relationship between age and the lateral wall thickness was
      not (P >0.05). The relationship between bladder volume and body mass index was
      significant (P = 0.0001, r = 0.2959). A strong positive and significant
      correlation was found between the anterior (P = 0.0001) and posterior (P = 0.001)
      wall thicknesses and body mass index, but the correlation between the lateral
      wall thickness and body mass index was not significant (P = 0.079, r = 0.113).
      CONCLUSIONS: Strong, positive correlations were found between the anterior and
      posterior wall detrusor thicknesses and increased age and body mass index, but
      the same correlations for lateral wall detrusor thickness were not found.

PMID- 17445668
TI  - Nuclear cystometrogram-determined bladder pressure at onset of vesicoureteral
      reflux predicts spontaneous resolution.
AB  - OBJECTIVES: The bladder pressure at the onset of reflux may reflect the
      competence of the ureterovesical junction. The predictive value of the bladder
      pressure at the onset of vesicoureteral reflux, as measured by nuclear
      cystometrography, was assessed relative to subsequent reflux resolution. METHODS:
      Nuclear cystometrograms of 67 children were reviewed to determine the presence of
      reflux, bladder pressure at the onset of reflux, and bladder volume at the onset
      of reflux. The data were analyzed for significant relationships between the
      nuclear cystometrogram results and patient outcomes using a Cox proportional
      hazards regression model, controlling for the duration of follow-up and for
      patients with bilateral reflux. RESULTS: Data were gathered for reflux occurring
      in 85 ureters. As expected, reflux of a greater grade was less likely to resolve
      spontaneously (P = 0.005). The pressure at the onset of reflux was also highly
      predictive of spontaneous resolution (P = 0.0005). Reflux occurring at greater
      pressures was more likely to resolve spontaneously, independent of the reflux
      grade or bladder volume at the onset of reflux. Patient age (P = 0.45),
      normalized volume of urine refluxed (P = 0.97), and normalized bladder volume at
      the onset of reflux (P = 0.18) were not significant predictors of reflux
      resolution. CONCLUSIONS: The findings of this report have demonstrated for the
      first time, to our knowledge, that the bladder pressure at the onset of
      vesicoureteral reflux, as determined by nuclear cystometrography, is a
      significant independent predictor of vesicoureteral reflux resolution in
      children.

PMID- 17445669
TI  - Umbilical stomal stenosis: a simple surgical revision technique.
AB  - Stenosis of stomas sited at the umbilicus presents a surgical challenge. A
      paucity of literature exists on the surgical management of this problem, despite
      its relatively frequent occurrence. A simple technique is described, using scar
      incision and advancement of an umbilical skin flap, to accomplish stomal
      revision.

PMID- 17445670
TI  - "Blind coning"--using the Stone Cone for removal of intramural ureteral calculi.
AB  - INTRODUCTION: To describe the otherwise heretical technique of "blind"
      nonureteroscopic extraction of calculi from the intramural ureter using a 7-mm
      diameter tapered coil called the "Stone Cone." TECHNICAL CONSIDERATIONS: After
      bypassing the stone and deploying the Stone Cone, slow traction was exerted. The
      Stone Cone's 5, 6, and 7-mm diameter coils and unique rotary action dilated the
      tunnel distal to the calculus and the 2, 3, and 4-mm stiffer coils caught the
      calculus and propelled it out of the transiently dilated intramural ureter. A
      safety feature is that the coils of the Stone Cone will unwind at greater than
      0.2-lb tension. Unlike the baskets, if a pressure greater than this is
      encountered, the Stone Cone will release the stone, preventing entrapment.
      CONCLUSIONS: In selected cases, use of the Blind-Cone to remove an intramural
      calculus can be a rapid, effective, and safe alternative to ureteroscopic
      management.

PMID- 17445671
TI  - Ectopic supraceliac renal artery take-off: imaging with digital subtraction
      angiography and computed tomography angiography.

PMID- 17445672
TI  - Primary seminal vesicle adenocarcinoma presenting as isolated metastasis to penis
      responding to chemotherapy and hormonal therapy.
AB  - We report a rare case of isolated penile metastasis from seminal vesicle
      adenocarcinoma associated with ipsilateral renal agenesis in a 62-year-old man.
      Imaging studies confirmed seminal vesicle origin, and biopsy revealed a papillary
      mucin-secreting adenocarcinoma, with cytokeratin 20 positivity and prostate
      specific antigen negativity. The sigmoidoscopy and metastatic workup findings
      were normal. The patient received six cycles of 5-fluorouracil, leucovorin, and
      oxaliplatin chemotherapy and underwent bilateral orchiectomy. The patient was
      symptomatically better, and the penile swelling and seminal vesicle mass had
      regressed considerably. He later developed multiple lung metastases and died of
      the disease.

PMID- 17445673
TI  - Primary seminal vesicle carcinoma detected at transurethral resection of
      prostate.
AB  - We present a case of primary seminal vesicle carcinoma detected at transurethral
      resection. The clinical presentation, radiologic findings, and pathologic
      features of these tumors are reviewed. Grossly, seminal vesicle carcinoma is
      poorly circumscribed and solid or solid/cystic and may be misinterpreted as an
      abscess or hemorrhage on radiologic examination. Although a definitive diagnosis
      often cannot be given until after complete resection, we describe the findings
      indicative of seminal vesicle origin, including papillary histologic
      architecture, sometimes with mucinous differentiation, and a characteristic
      immunophenotype positive for CA-125 and cytokeratin 7, but negative for prostate
      specific antigen and cytokeratin 20.

PMID- 17445674
TI  - Urothelial carcinoma "nested variant" of renal pelvis and ureter.
AB  - The nested variant of urothelial carcinoma is a rare type of urothelial invasive
      carcinoma. It is characterized by islands of discrete to moderate atypical
      urothelial cells that strongly simulate von Brunn nests and invade to the lamina
      propria or deeper. Almost all described cases have been located in the bladder.
      We report a case of nested variant of urothelial carcinoma of the renal pelvis
      and ureter, synchronous with high-grade urothelial papillary carcinoma.

PMID- 17445675
TI  - Percutaneous radiofrequency ablation of tumor in transplanted kidney.
AB  - Treatment options for tumors in allograft kidneys include radical nephrectomy or
      nephron-sparing surgery. Nephron-sparing procedures relieve the patient of the
      necessity of immediate dialysis. Partial nephrectomy is technically challenging
      and potentially difficult because of existing comorbidities and adhesions from
      previous surgery. Probe ablation is technically simpler and is associated with
      lower morbidity, shorter hospitalization, and reduced convalescence compared with
      open partial nephrectomy of a renal allograft. We present an interesting case
      with a synchronous finding of a papillary renal cancer in a native and allograft
      kidney, in which the allograft tumor was treated with percutaneous radiofrequency
      ablation.

PMID- 17445676
TI  - Scrotal ulcer after intraperitoneal hyperthermic chemotherapy.
AB  - Tumor cytoreduction combined with intraperitoneal hyperthermic chemotherapy has
      been shown to be an effective method to delay the progression of peritoneal
      carcinomatosis. We describe 2 cases of painful scrotal ulcer after tumor
      debulking and intraperitoneal infusion of mitomycin-C for treatment of metastatic
      abdominal malignancies. Although the pathogenesis is unknown, the awareness of
      its presence and early signs of clinical presentations by clinicians is very
      important.

PMID- 17445677
TI  - Methicillin-resistant Staphylococcus aureus prostatitis.
AB  - Prostatitis is a common condition that is associated with a poor quality of life.
      A recent National Institutes of Health Consensus Panel classified prostatitis
      into the categories of acute bacterial, chronic bacterial, chronic nonbacterial,
      and asymptomatic. Bacterial prostatitis is usually caused by Escherichia coli and
      other gram-negative bacteria, but it is not frequently caused by Staphylococcus
      aureus. Community-acquired methicillin-resistant S. aureus infections are
      increasing. Moreover, 2 cases of methicillin-resistant S. aureus prostatic
      abscesses have been reported. We describe what we believe to be the first case of
      a patient with community-acquired methicillin-resistant S. aureus acute
      prostatitis as determined by cultures of prostatic tissue, blood, and nares.

PMID- 17445678
TI  - Laparoscopic heminephrectomy for renal cell carcinoma in cross-fused ectopic
      kidney.
AB  - Crossed renal ectopia is a rare congenital malformation. We report a case of
      renal cell carcinoma in a 51-year-old man with right-to-left crossed fused renal
      ectopia. The patient was treated with ultrasound-guided laparoscopic
      heminephrectomy. Postoperative three-dimensional computed tomography showed
      normal perfusion of the remaining part of the kidney, with good excretion of
      contrast from both units of the cross-fused kidney.

PMID- 17445679
TI  - Noninfective cutaneous granuloma with leuprorelin acetate--reality or myth.
AB  - We present our experience with 7 patients who developed injection site granuloma
      with leuprorelin acetate injection. Although isolated case reports exist, this is
      the largest collection of cases from a single center. The exact mechanism of the
      granuloma formation is not well understood, although theories are associated with
      the vehicle used for injection. Our discussion focuses on the nature of the
      granuloma formation and its etiology. The reaction appears to be more common with
      leuprorelin acetate than with other forms of luteinizing hormone-releasing
      hormone analogues.

PMID- 17445680
TI  - Treatment of posttraumatic high-flow priapism in 8-year-old boy with percutaneous
      ultrasound-guided thrombin injection.
AB  - Treatment of high-flow priapism varies and has included transcatheter
      embolization when conservative approaches fail. We present the case of an 8-year
      old boy with high-flow priapism, who was treated with ultrasound-guided thrombin
      injection because of encouraging experience with the method obtained when
      treating aneurysms and pseudoaneurysms. This procedure appears to be a useful
      alternative to transcatheter embolization and results in no radiation exposure.

PMID- 17445681
TI  - Bladder cancer cell invasion is enhanced by cross-talk with fibroblasts through
      hepatocyte growth factor.
AB  - OBJECTIVES: To examine the effects of fibroblast-derived humoral factors,
      especially hepatocyte growth factor (HGF), on the invasive potential of bladder
      cancer cells. Stromal cells in cancer tissue are thought to play an important
      role in the transformation and invasion of cancer cells. METHODS: The influence
      of fibroblast cells (TIG-1 cells) and HGF on the invasive potential of bladder
      cancer cells (5637, T24, J82, HT1376, and MGHU-1 cells) was evaluated by in vitro
      cell invasion assay. The expression of HGF and c-Met, which is the receptor of
      HGF, was examined by reverse transcriptase-polymerase chain reaction. To clarify
      the relationship between the serum HGF level and invasive bladder cancer, we
      measured the serum concentrations of HGF in patients with bladder cancer without
      metastatic disease and normal controls, using an enzyme-linked immunosorbent
      assay. RESULTS: The in vitro cell invasion assay showed that the number of
      invading bladder cancer cells was significantly increased by the conditioned
      medium (CM) of the fibroblast cells. HGF neutralization antibody partially
      inhibited the enhancement of invasiveness by fibroblast CM. The CM of fibroblasts
      cultured with bladder cancer CM stimulated cancer cell invasion more strongly
      (with increased HGF secretion) than did the CM of fibroblasts cultured without
      bladder cancer CM. The serum HGF levels were significantly greater in patients
      with muscle-invasive bladder cancer (regardless of tumor size) than in patients
      with non-muscle-invasive bladder cancer. CONCLUSIONS: The present results have
      suggested that bladder cancer cell invasion is enhanced by cross-talk with
      fibroblasts through humoral factors, including HGF. Elucidation of this mechanism
      could lead to novel therapeutic strategies for bladder cancer.

PMID- 17445682
TI  - Relaxation of human detrusor muscle by selective beta-2 and beta-3 agonists and
      endogenous catecholamines.
AB  - OBJECTIVES: The goal of this study was to identify potent relaxant agents of the
      human detrusor muscle. Therefore, the relaxant effects of different selective
      beta (beta)-adrenoceptor agonists were examined. Also, the relaxant effects of
      the endogenous catecholamines were investigated to functionally characterize the
      beta-adrenoceptor subtype mainly responsible for adrenergic-mediated relaxation
      in the detrusor muscle of humans. METHODS: Experiments were performed on muscle
      strips of human detrusor suspended in a tissue bath. The tissue originated from
      patients who had undergone total cystectomy. The selective beta3-agonists BRL
      37344, ZD 7114, and CGP 12177, the selective beta2-agonists terbutaline and
      clenbuterol, and the nonselective beta-agonist isoprenaline were investigated.
      Concentration-relaxation curves of the catecholamines were performed to determine
      the rank order of potency. RESULTS: The maximal relaxation induced by BRL 37344,
      ZD 7114, and CGP 12177 was 36%, 39%, and 37%, respectively. The corresponding pD2
      values were 6.73, 4.82, and 6.09, respectively. Terbutaline and clenbuterol
      induced a maximal relaxation of 48% and 27%, and their pD2 value was 4.97 and
      5.34, respectively. Isoprenaline, adrenaline, and noradrenaline induced a maximal
      relaxation of 72%, 58%, and 79%, respectively. The corresponding pD2 values were
      6.18, 6.16, and 6.09, respectively. Because their differences were not
      significant, no rank order of potency was determined. CONCLUSIONS: Beta
      adrenergic agonists are potent relaxant agents of the human detrusor muscle in
      vitro. Both beta2 and beta3-adrenoceptors contribute to adrenergic-mediated
      relaxation. Our results point to a slightly greater role for the beta3-receptor
      in human detrusor muscle.

PMID- 17445683
TI  - Rho-kinase inhibition suppresses potassium chloride-induced bladder hyperactivity
      in a rat model.
AB  - OBJECTIVES: The molecular mechanisms by which potassium induces urinary bladder
      hyperactivity are not clear. In the present study, we tested our hypothesis that
      potassium chloride (KCl)-induced bladder hyperactivity might be mediated through
      a calcium-sensitizing RhoA-Rho-kinase pathway in an in vivo animal model using
      urodynamic parameters. METHODS: Two groups of adult male rats (n = 8) were
      anesthetized, their bladder exteriorized, and a saline-filled Intracath fixed
      into the bladder dome. This Intracath was connected to a pressure transducer and
      an infusion pump. Continuous filling cystometrograms were performed by infusing
      warm saline (0.04 mL/min) to obtain baseline data on each rat. The number of
      contractions per unit time (intercontractile intervals in seconds), pressure
      threshold, and peak pressure during micturition were recorded. To create bladder
      hyperactivity, protamine sulfate (30 mg/mL) followed by KCl (500 mM) was infused
      intravesically, and a continuous filling cystometrogram was again recorded. Y
      27632, a specific RhoA-Rho-kinase inhibitor, was administered either intra
      arterially (group 1) or intravesically (group 2) to each rat, and an additional
      continuous filling cystometrogram was recorded with KCl (500 mM) to observe the
      effects of Rho-kinase inhibition on bladder contractility. RESULTS: Intravesical
      KCl infusion after protamine exposure resulted in significantly greater
      contractions and decreased the intercontractile interval (P <0.05). Y-27632
      administration attenuated the effect of KCl on the contractions and
      intercontractile interval and decreased the mean pressure threshold. CONCLUSIONS:
      Suppression of KCl-induced bladder contractility by the Rho-kinase inhibitor Y
      27632 confirmed the involvement of this novel calcium-sensitizing RhoA-Rho-kinase
      pathway in mediating these smooth muscle contractions.

PMID- 17445684
TI  - Heterogeneous activation of MMP-9 due to prostate cancer-bone interaction.
AB  - OBJECTIVES: To determine whether matrix metalloproteinase (MMP)-9 activation
      resulting from prostate cancer cell-bone interaction is dependent on the tumor
      cell type and/or the nature of the bone microenvironment. METHODS: In vitro co
      cultures of human prostate cancer cells (PC3 and C4-2B) and mouse, human fetal,
      or human adult tissues were performed. In vivo the tumor cells were intratibially
      injected in SCID mice or intraosseously inoculated into fetal or adult bone
      xenografts in SCID mice. MMP-2 and MMP-9 expression and activation were
      determined by gelatin zymography in conditioned media obtained in vitro and in
      lysates derived from the in vivo studies at different time points. RESULTS:
      Activation of MMP-9 occurred when PC3 cells interacted with human adult or fetal
      bone, either in vitro or in vivo at early time points. With C4-2B cells,
      activation of MMP-9 only happened in the human adult bone microenvironment at
      early time points after intraosseous inoculation of tumor cells. No activation of
      MMP-9 occurred when PC3 or C4-2B cells interacted with mouse bone, either in
      vitro or in vivo. CONCLUSIONS: The results of our study have shown that the
      activation of MMP-9 when human prostate cancer cells interact with bone depends
      on the particular identity of the tumor cells and the type of bone tissue used.
      These findings have broad implications for experimental models attempting to
      define tumor-microenvironmental interactions in bone metastasis.

PMID- 17445685
TI  - Innovative single-armed suture technique for microsurgical vasoepididymostomy.
AB  - OBJECTIVES: Vasoepididymostomy outcomes are heavily dependent on the surgeon's
      microsurgical experience and skill. To avoid back-walling the tubular lumen, the
      needles are generally placed inside-out through the vasal lumen using double
      armed microsutures. These double-armed sutures for infertility microsurgery are
      very expensive and may be difficult to obtain. We describe a randomized trial
      that used a novel single-armed suture placement pattern for vasoepididymostomy.
      METHODS: Male adult Wistar rats underwent vasectomy. Two weeks later,
      vasoepididymostomies were performed using either a single-armed longitudinal
      intussusception vasoepididymostomy (n = 6) or a standard double-armed
      longitudinal intussusception vasoepididymostomy (n = 6) technique. After 9 weeks,
      patency was assessed functionally by evaluating for motile sperm distal to the
      anastomosis. If no motile sperm were visible, the mechanical patency of the
      anastomoses was tested by the ability of methylene blue to pass through the
      surgical anastomosis. RESULTS: The patency rate for the double-armed
      vasoepididymostomy group was 100% (6 of 6) compared with 83.3% (5 of 6) for the
      single-armed vasoepididymostomy group. This difference was not significant (P =
      0.50). Sperm granulomas were found in three (50%) of six anastomoses in the
      double-armed group and five (83%) of six anastomoses in the single-armed
      vasoepididymostomy group (P = 0.27). The mean operative times for the double and
      single-armed longitudinal intussusception vasoepididymostomy techniques were
      similar (35 minutes versus 43 minutes; P = 0.39). CONCLUSIONS: The results of our
      study have shown that the single-armed suture technique to perform
      vasoepididymostomy is almost as effective as the double-armed technique. Although
      we still prefer to use double-armed sutures, we believe that this is a practical
      and effective alternative when specialized double-armed microsurgical sutures are
      not available.

PMID- 17445687
TI  - Isolation and subfractionation of mitochondria from animal cells and tissue
      culture lines.

PMID- 17445688
TI  - Purification and subfractionation of mitochondria from the yeast Saccharomyces
      cerevisiae.

PMID- 17445689
TI  - Isolation and subfractionation of mitochondria from plants.

PMID- 17445690
TI  - Biochemical assays of respiratory chain complex activity.

PMID- 17445691
TI  - Polarographic assays of respiratory chain complex activity.

PMID- 17445692
TI  - Optical imaging techniques (histochemical, immunohistochemical, and in situ
      hybridization staining methods) to visualize mitochondria.

PMID- 17445694
TI  - Measurement of the ratio of lactate to pyruvate in skin fibroblast cultures.

PMID- 17445693
TI  - Assay of mitochondrial ATP synthesis in animal cells and tissues.

PMID- 17445695
TI  - Assays of fatty acid beta-oxidation activity.

PMID- 17445696
TI  - Biochemical assays for mitochondrial activity: assays of TCA cycle enzymes and
      PDHc.

PMID- 17445697
TI  - Assays of cardiolipin levels.

PMID- 17445698
TI  - Measurement of VDAC permeability in intact mitochondria and in reconstituted
      systems.

PMID- 17445699
TI  - Methods for studying iron metabolism in yeast mitochondria.

PMID- 17445700
TI  - Imaging of mitochondrial polarization and depolarization with cationic
      fluorophores.

PMID- 17445701
TI  - Biosensors for the detection of calcium and pH.

PMID- 17445702
TI  - Measurement of membrane permeability and the permeability transition of
      mitochondria.

PMID- 17445703
TI  - Luciferase expression for ATP imaging: application to cardiac myocytes.

PMID- 17445704
TI  - Measurement of reactive oxygen species in cells and mitochondria.

PMID- 17445705
TI  - Measurements of the antioxidant enzyme activities of superoxide dismutase,
      catalase, and glutathione peroxidase.

PMID- 17445706
TI  - Methods for measuring the regulation of respiration by nitric oxide.

PMID- 17445707
TI  - Methods for determining the modification of protein thiols by reactive lipids.

PMID- 17445708
TI  - Detection of mutations in mtDNA.

PMID- 17445709
TI  - Diagnostic assays for defects in mtDNA replication and transcription in yeast and
      humans.

PMID- 17445710
TI  - Microdissection and analytical PCR for the investigation of mtDNA lesions.

PMID- 17445711
TI  - Transmitochondrial technology in animal cells.

PMID- 17445712
TI  - Genetic transformation of Saccharomyces cerevisiae and Chlamydomonas reinhardtii
      mitochondria.

PMID- 17445713
TI  - Generation of transmitochondrial mice: development of xenomitochondrial mice to
      model neurodegenerative diseases.

PMID- 17445714
TI  - In vivo and in organello analyses of mitochondrial translation.

PMID- 17445715
TI  - Visualization of mitochondria in budding yeast.

PMID- 17445716
TI  - Visualization and quantification of mitochondrial dynamics in living animal
      cells.

PMID- 17445717
TI  - Cell-free assays for mitochondria-cytoskeleton interactions.

PMID- 17445718
TI  - In vitro assays for mitochondrial fusion and division.

PMID- 17445719
TI  - Electrophoretic methods to isolate protein complexes from mitochondria.

PMID- 17445720
TI  - Analysis of protein-protein interactions in mitochondria.

PMID- 17445721
TI  - Analysis and prediction of mitochondrial targeting signals.

PMID- 17445722
TI  - Import of proteins into mitochondria.

PMID- 17445723
TI  - Appendix 1. Basic properties of mitochondria.

PMID- 17445724
TI  - Appendix 2. Direct and indirect inhibitors of mitochondrial ATP synthesis.

PMID- 17445725
TI  - Appendix 3. Linearized maps of circular mitochondrial genomes from representative
      organisms.

PMID- 17445726
TI  - Appendix 4. Mitochondrial genetic codes in various organisms.

PMID- 17445727
TI  - Appendix 5. Gene products present in mitochondria of yeast and animal cells.

PMID- 17445728
TI  - Appendix 6. Changes in the mitochondrial transcriptome and proteome under various
      stresses and growth conditions.

PMID- 17445730
TI  - Mouth-to-tracheostomy tube ventilation in an emergency situation.

PMID- 17445732
TI  - Anatomy and examination of the spine.
AB  - A basic knowledge of anatomy of the spine is an essential ingredient to
      understanding disease and disorders of the spine. The second section of this
      article details the neurologic examination of the spine in patients with neck and
      back pain. Understanding anatomic concepts leads to an informed examination of
      the spine. Through the history and neurologic examination, many disorders of
      spinal anatomy can be diagnosed.

PMID- 17445733
TI  - Epidemiology and risk factors for spine pain.
AB  - Low back and neck pain is a common problem and one of enormous social,
      psychologic, and economic burden. It is estimated that 15% to 20% of adults have
      back pain during a single year and 50% to 80% experience at least one episode of
      back pain during a lifetime. Low back pain afflicts all ages, from adolescents to
      the elderly, and is a major cause of disability in the adult working population.
      Risk factors for developing spine pain are multidimensional; physical attributes,
      socioeconomic status, general medical health and psychologic state, and
      occupational environmental factors all contribute to the risk for experiencing
      pain.

PMID- 17445734
TI  - Cervical radiculopathy.
AB  - Cervical radiculopathy is a condition encountered commonly in the evaluation of
      neck pain that may result in significant discomfort and functional deficits.
      Although the long-term prognosis of this condition is favorable, a standardized
      approach to therapy is important to minimize unnecessary tests and identify
      patients who require more urgent intervention. Patient education, pain control,
      and physical therapy are the first line of therapy. Patients who have protracted
      pain or significant functional deficits may require a more thorough evaluation,
      including imaging, electrodiagnostic testing, and, possibly, surgical referral.
      This article outlines the basic clinical, diagnostic, and therapy considerations
      in the evaluation of cervical radiculopathy.

PMID- 17445735
TI  - Lumbosacral radiculopathy.
AB  - Lumbosacral radiculopathy is one of the most common disorders evaluated by
      neurologists and is a leading referral diagnosis for the performance of
      electromyography. Although precise epidemiologic data are difficult to establish,
      the prevalence of lumbosacral radiculopathy is approximately 3% to 5%,
      distributed equally in men and women. Degenerative spondyloarthropathies are the
      principal underlying cause of these clinical syndromes and are increasingly
      commonplace with age. Men are most likely to develop symptoms in their 40s,
      whereas women are affected most commonly between ages 50 and 60. The clinical
      presentation and initial management of lumbosacral radiculopathies of various
      etiologies are discussed.

PMID- 17445736
TI  - Lumbar spinal stenosis.
AB  - Lumbar spinal stenosis may be congenital or acquired. A classic clinical
      presentation is described as neurogenic claudication. Physical signs of sensory
      loss, weakness, and attenuation of reflexes often are mild and limited in
      distribution. Neuroimaging of the lumbosacral spine with MRI and
      electrodiagnostic (electromyographic [EMG]) tests are the most informative
      diagnostic modalities. Conservative management often is successful, but surgical
      decompression may be indicated in refractory cases.

PMID- 17445737
TI  - Neck and back pain: musculoskeletal disorders.
AB  - In this article, non-neurologic causes of neck and back pain are reviewed.
      Musculoskeletal pain generators include muscle, tendon, ligament, intervertebral
      disc, articular cartilage, and bone. Disorders that can produce neck and back
      pain include muscle strain, ligament sprain, myofascial pain, fibromyalgia, facet
      joint pain, internal disc disruption, somatic dysfunction, spinal fracture,
      vertebral osteomyelitis, and polymyalgia rheumatica. Atlantoaxial instability and
      atlanto-occipital joint pain are additional causes of neck pain. Back pain
      resulting from vertebral compression fracture, Scheuermann's disease,
      spondylolysis and spondylolisthesis, pregnancy, Baastrup's disease, sacroiliac
      joint dysfunction, and sacral stress fracture is discussed.

PMID- 17445738
TI  - Neck and low back pain: neuroimaging.
AB  - Spine imaging accounts for a major share of expenses related to neck and back
      pain. Improving image quality translates into better morphologic evaluation of
      the spine. Unfortunately, the morphologic abnormalities on spine imaging are
      common and nonspecific, obscuring the relevance to patient symptomatology.
      Furthermore, distinction between degenerative and age-related changes is not
      clear. The key is clinical correlation of imaging findings. This article presents
      a concise and illustrated discussion of spinal neuroimaging related to neck and
      back pain, with emphasis on degenerative disease.

PMID- 17445739
TI  - The electrodiagnosis of cervical and lumbosacral radiculopathy.
AB  - This article reviews the usefulness of the electrodiagnostic examination in
      patients who have suspected cervical and lumbosacral radiculopathy. This study
      can verify the presence and severity of radiculopathy, determine which levels are
      involved, and provide an electrodiagnostic correlate to imaging abnormalities. A
      practical approach for conducting the nerve conduction portion and needle
      electrode examination in these patients is discussed.

PMID- 17445740
TI  - Nonsurgical interventions for spine pain.
AB  - Nonsurgical, conservative approaches to spine pain include medication and
      physical therapy. In addition, several invasive procedures have been developed to
      provide relief when conservative options fail. These include facet joint
      injection and radiofrequency ablation techniques, translaminar and transforaminal
      epidural corticosteroid injections, and intradiscal coagulation procedures.
      Controlled studies to assess the effectiveness of some of these therapeutic
      modalities have been performed.

PMID- 17445741
TI  - Surgical management of neck and low back pain.
AB  - Surgical intervention for neck pain and low back pain may be of benefit to some
      patients. It should be considered, however, only in cases where medical
      management has failed and there is a clearly identifiable anatomic lesion that
      likely is the pain generator. Indications, preoperative evaluation, and common
      surgical procedures are reviewed.

PMID- 17445742
TI  - Physical medicine and complementary approaches.
AB  - Medical approaches to the treatment of spine pain are the cornerstone of therapy
      for neck and back pain. Although these techniques are used widely, seldom have
      they been subjected to the scrutiny of careful randomized and controlled clinical
      trials. The costs of complementary treatments, such as spinal manipulation,
      massage therapy, and acupuncture, now are reimbursed by many medical insurance
      providers, but these modalities lack much scientific support. Physical medicine
      and complementary treatment modalities and some of the scientific studies aimed
      at assessing their effectiveness are reviewed.

PMID- 17445743
TI  - Chronic pain management in spine disorders.
AB  - Chronic nonmalignant pain is less a symptom of a disease than a disease in
      itself. Accordingly, successful treatments rely less on identifying underlying
      pathology than on treating neural causes of pain amplification, psychologic
      causes of disability, and the sequelae of deconditioning and psychiatric illness.
      The outcome, when such treatment is provided, is remarkably favorable.

PMID- 17445744
TI  - Nonverbal communication--An important key to in-depth understanding of provider
      patient interaction.

PMID- 17445745
TI  - Parents' awareness of and knowledge about young children's urinary tract
      infections.
AB  - OBJECTIVE: To provide insight into parents' awareness of and knowledge about
      urinary tract infections (UTIs) in young children. METHODS: Twenty interviews
      with parents who had a child recently diagnosed with a UTI were audiotaped,
      transcribed verbatim, and qualitatively analysed. RESULTS: Most parents knew the
      typical symptoms related to UTI. But, according to the parents, neither they nor
      all general practitioners (GPs) thought of a UTI in case of atypical symptoms.
      The awareness that UTI can be a serious illness usually came to parents later,
      partly because health care workers often did not explicitly mention this.
      According to the parents, health care workers should be more aware of UTIs in
      children. Parents felt that health education or mass screening might not be
      desirable because it would increase anxiety or would be perceived as not
      relevant. CONCLUSION: Parents could not consistently recognise UTI in their
      children and were most times unaware of the possible consequences of a UTI.
      Nevertheless, parents were sceptical about health education and mass screening.
      PRACTICE IMPLICATIONS: There seems little scope for health education addressed at
      parents or screening for UTI in young children. Instead, physicians and nurses
      should be alert for the possibility of UTIs in young children, and more
      information should be given once a UTI is diagnosed.

PMID- 17445746
TI  - Heterologous expression and comparative characterization of the human neuromedin
      U subtype II receptor using the methylotrophic yeast Pichia pastoris and
      mammalian cells.
AB  - Neuromedin U (a neuropeptide) plays regulatory roles in feeding, anxiety, smooth
      muscle contraction, blood flow and pain. The physiological actions of NmU are
      mediated via two recently identified G protein-coupled receptors namely the
      neuromedin U type 1 receptor (NmU(1)R) and the neuromedin U type 2 receptor
      (NmU(2)R). Despite their crucial roles in cell physiology, structural information
      on these receptors is limited, mainly due to their low expression levels in
      native tissues. Here, we report the overexpression of the human NmU(2)R in the
      methylotrophic yeast Pichia pastoris and baby hamster kidney (BHK) cells using
      the Semliki Forest virus (SFV) system. The recombinant receptor was expressed as
      a fusion protein with three different affinity tags namely, the Flag tag, the
      histidine 10 tag and the biotinylation domain of Propionobacterium shermanii.
      Expression level of the recombinant receptor was 6-9pmol/mg under optimized
      conditions, which is significantly higher than the expression level in the native
      tissues. The recombinant receptor binds to its endogenous ligand neuromedin U
      with high affinity (Kd=0.8-1.0nM) and the binding constant for the recombinant
      receptor is similar to that of the wild type NmU(2)R. Enzymatic deglycosylation
      suggested that the recombinant NmU(2)R was glycosylated in P. pastoris, but not
      in BHK cells. Confocal laser scanning microscopy and immunogold labelling
      experiment revealed that the recombinant receptor was predominantly localized in
      the intracellular membranes. To our knowledge, this is the first report of
      heterologous overexpression of an affinity tagged recombinant NmU(2)R and it
      should facilitate further characterization of this receptor.

PMID- 17445747
TI  - Gastric ischemia treated with superior mesenteric artery revascularization.

PMID- 17445748
TI  - Spontaneous rupture of intrahepatic aneurysm.

PMID- 17445749
TI  - Fecal incontinence in a 56-year-old female executive.

PMID- 17445750
TI  - "Maintenance" treatment for patients with cirrhosis related to hepatitis C.

PMID- 17445752
TI  - Gastrointestinal symptoms after infectious diarrhea: a five-year follow-up in a
      Swedish cohort of adults.
AB  - BACKGROUND & AIMS: Gastrointestinal infection is a well-recognized trigger for
      functional bowel disorder. This study evaluated gastrointestinal symptoms and
      risk factors for their development after diarrheal disease of proven or strongly
      suspected infectious etiology in adults. METHODS: The cohort of patients was
      derived from a previous study that determined the rate at which enteropathogens
      could be isolated at the time of diarrheal disease in adults. After 5 years, 717
      of 851 patients were accessible for a questionnaire asking for persistence of
      gastrointestinal symptoms. RESULTS: Of 508 returned questionnaires, 333 were from
      patients with no previous gastrointestinal complaints. Forty-one (12%) of them
      had gastrointestinal symptoms for 3 months or more after the infectious diarrhea,
      and 31 (9%) still had symptoms at the end of the follow-up period. Irritable
      bowel syndrome was most common (68%), but other functional bowel disorder
      diagnoses were found in all but one of the others. Female gender (odds ratio,
      2.65, 95% confidence interval, 1.28-5.50) and use of antibiotic treatment (odds
      ratio, 2.37; 95% confidence interval, 1.07-5.25) were risk factors for
      development of postinfectious functional bowel disorder. No increase in risk was
      associated with the type of enteropathogen causing diarrhea. CONCLUSIONS:
      Infectious diarrhea in previously healthy adults carried a substantial risk of
      triggering postinfectious functional bowel disorder. Irritable bowel syndrome was
      the most common, but other functional bowel disorders were also found. We did not
      find any new clinical tools that would facilitate the prediction of long-standing
      symptoms.

PMID- 17445751
TI  - Significant enhancement of esophageal pre-epithelial defense by tegaserod:
      implications for an esophagoprotective effect.
AB  - BACKGROUND & AIMS: Tegaserod, a serotonin 5-hydroxytryptamine (5-HT)4 receptor
      agonist, is thought to stimulate intestinal secretions. The aim of the current
      study was to assess the effect of tegaserod vs placebo on salivary and esophageal
      protective factors in patients with gastroesophageal reflux disease (GERD).
      METHODS: This study was a randomized, double-blind, placebo-controlled, cross
      over trial in 38 GERD patients treated with tegaserod 6 mg twice a day vs
      placebo. Salivary samples were collected basally and during mastication. In
      addition, in 32 GERD patients, salivary and esophageal secretions also were
      collected during infusion of NaCl, HCl/pepsin, and NaCl in a consecutive fashion
      using a specially designed esophageal catheter. Saliva and esophageal perfusates
      were assessed for the pH, volume, content of buffers, protein, mucin, epidermal
      growth factor (EGF), transforming growth factor alpha (TGFalpha), and
      prostaglandin E (PGE)2 and analyzed statistically. RESULTS: Salivary flow rates
      during administration of tegaserod increased over corresponding values during
      both basal conditions (P < .01) and mastication (P < .001). The rate of secretion
      of salivary bicarbonate and nonbicarbonate buffers also increased in basal
      conditions (P < .001 and P < .01, respectively) and during mastication (P < .05
      and P = .05). Salivary EGF increased during mastication (P < .05), whereas PGE2
      and TGF alpha increased in basal conditions (P < .05 and P < .01). Esophageal
      perfusate volumes increased during administration of tegaserod in basal
      conditions (P < .05), whereas esophageal EGF secretion increased after mucosal
      exposure to HCl/pepsin and subsequent final perfusion with NaCl (P < .05).
      CONCLUSIONS: Significant stimulatory impact of 5-HT4 agonist on several salivary
      protective factors as well as esophageal EGF secretion may have
      esophagoprotective implications in patients with GERD and may help to address new
      therapies in the future.

PMID- 17445753
TI  - Risk of irritable bowel syndrome after an episode of bacterial gastroenteritis in
      general practice: influence of comorbidities.
AB  - BACKGROUND & AIMS: Given the discrepant estimates of incidence rates of irritable
      bowel syndrome (IBS) after gastroenteritis (GE), we performed a cohort study to
      quantify this risk in community subjects and to identify factors acting as
      modifiers of this effect. METHODS: In a previous study, we identified patients
      aged 20-74 years with a first ever episode of bacterial GE during 1992-2001. We
      excluded patients with a history of bowel disease and cancer, resulting in a
      cohort of 5894 individuals with GE. From the same source population, a control
      group free of GE was sampled. We followed up the 2 cohorts to identify incident
      cases of IBS. A nested case-control analysis was performed to quantify the role
      of potential risk factors. RESULTS: During a mean follow-up period of 4.1 years,
      1105 patients developed IBS. The incidence rate of IBS after an episode of
      bacterial GE was 98.2 per 10,000 person-years, and 45.3 per 10,000 person-years
      in the comparison cohort. The adjusted relative risk of IBS associated with
      bacterial GE was 2.2 (1.5-2.9) compared with the control cohort. The nested case
      control analysis adjusting for additional risk factors produced similar results
      (odds ratio, 1.8; 95% confidence interval, 1.5-2.1). The risk of IBS after GE was
      increased significantly in patients with depression, anxiety, stress or sleep
      disorders, prior gastrointestinal morbidity, or prolonged use of antibiotics.
      CONCLUSIONS: The risk of IBS in community individuals after having bacterial GE
      was two fold greater in the general population. Pre-existing psychologic and
      gastrointestinal comorbidities independently increase this risk of developing
      IBS.

PMID- 17445754
TI  - 13C-mixed triglyceride breath test to assess oral enzyme substitution therapy in
      patients with chronic pancreatitis.
AB  - BACKGROUND & AIMS: Malnutrition persists in most patients with chronic
      pancreatitis despite an adequate clinical response to oral pancreatic enzyme
      substitution therapy. Our aims were to analyze the accuracy of the 13C-mixed
      triglyceride breath test as a tool for evaluating the effect of enzyme therapy on
      fat digestion in chronic pancreatitis, and to analyze the impact of modifying the
      therapy according to the breath test on patients' nutritional status. METHODS:
      The accuracy of the breath test for monitoring the effect of therapy was
      evaluated prospectively in 29 patients with maldigestion secondary to chronic
      pancreatitis by using the coefficient of fat absorption as the gold standard.
      Therapy was modified to obtain a normal breath test result in a further 20
      chronic pancreatitis patients with malnutrition despite an adequate clinical
      response to the enzyme therapy; the impact of this therapeutic modification on
      patients' nutritional status was evaluated. RESULTS: The coefficient of fat
      absorption and breath test results were similar when assessing fat absorption
      before and during treatment. Modification of the enzyme therapy to normalize fat
      absorption as assessed by the breath test in the second group of 20 patients was
      associated with a significant increase of body weight (P < .001), and serum
      concentrations of retinol binding protein (P < .001) and prealbumin (P < .001).
      CONCLUSIONS: The 13C-mixed triglyceride breath test is an accurate method to
      evaluate the effect of enzyme therapy on fat digestion. This method is simpler
      than the standard fecal fat test to assess therapy in patients with pancreatic
      exocrine insufficiency. Normalizing fat absorption improves nutrition in these
      patients.

PMID- 17445756
TI  - Epstein-Barr virus-associated lymphoma developed shortly after immunosuppressive
      treatment for ulcerative colitis.

PMID- 17445757
TI  - Which is the better strategy in patients with cystic pancreas lesions?

PMID- 17445759
TI  - Multiphase flow in microfluidic systems --control and applications of droplets
      and interfaces.
AB  - Micro- and nanotechnology can provide us with many tools for the production,
      study and detection of colloidal and interfacial systems. In multiphase flow in
      micro- and nanochannels several immiscible fluids will be separated from each
      other by flexible fluidic interfaces. The multiphase coexistence and the small
      volume confinement provide many attractive characteristics. Multiphase flow in
      microfluidic systems shows a complicated behavior but has many practical uses
      compared to a single-phase flow. In this paper, we discuss the methods of
      controlling multiphase flow to generate either micro- or nano-droplets (or
      bubbles) or stable stratified interfaces between fluidic phases. Furthermore,
      applications of the droplets and interfaces in microchannels are summarized.

PMID- 17445760
TI  - DNA entrapped polypyrrole-polyvinyl sulfonate film for application to
      electrochemical biosensor.
AB  - Double-stranded calf thymus (dsCT)-DNA was electrochemically entrapped into
      polypyrrole-polyvinyl sulfonate (PPy-PVS) films deposited onto indium tin oxide
      (ITO) coated glass plates. These dsCT-DNA entrapped PPy-PVS/ITO films were
      characterized using cyclic voltammetry, UV-visible, Fourier transform infrared
      (FT-IR), scanning tunneling microscopy (STM), and electrochemical impedance
      measurements. Attempts made to use these dsCT-DNA entrapped PPy-PVS/ITO films for
      detection of 2-aminoanthracene (0.001-6.0 ppm) and 3-chlorophenol (0.01-55.0 ppm)
      revealed a response time of 30s and a shelf life of approximately 25 weeks when
      stored under desiccated conditions at 25 degrees C. The addition of salts such as
      Ca(2+) (250 ppm), Mg(2+) (200 ppm), Cl(-) (1560 ppm), and Na(+) (150 ppm) ions
      contained in water does not affect the observed amperometric response of the
      disposable dsCT-DNA entrapped PPy-PVS film-based electrochemical biosensor.

PMID- 17445761
TI  - Macromolecular crowding and its influence on possible reaction mechanisms in
      photosynthetic electron flow.
AB  - The diffusion of plastoquinol and its binding to the Qo site of the cyt bf
      complex in the course of photosynthetic electron transport was studied by
      following the sigmoidal flash-induced re-reduction kinetics of P700 after
      previous oxidation of the intersystem electron carriers. The data resulting from
      these experiments were matched with a simulation of electron transport using
      Monte Carlo techniques. The simulation was able to account for the experimental
      observations. Two different extreme cases of reaction mechanism at the Qo site
      were compared: a diffusion limited collisional mechanism and a non-diffusion
      limited tight binding mechanism. Assuming a tight binding mechanism led to best
      matches due to the high protein density in thylakoids. The varied parameters
      resulted in values well within the range of published data. The results emphasise
      the importance of structural characteristics of thylakoids in models of electron
      transport.

PMID- 17445762
TI  - Iron deficiency influences the course of malaria in Plasmodium berghei infected
      mice.
AB  - Iron deficiency accelerates suicidal erythrocyte death, which is evident from
      phosphatidylserine exposure. The present study explored whether iron deficiency
      compromises intraerythrocytic growth of Plasmodium and enhances death of infected
      erythrocytes thus influencing the course of malaria. As a result,
      phosphatidylserine exposure is increased in Plasmodium falciparum infected human
      erythrocytes, an effect significantly more marked in iron deficiency. Moreover,
      iron deficiency impairs in vitro intraerythrocytic growth and infection of
      erythrocytes. In mice, iron-deficient erythrocytes are more rapidly cleared from
      circulating blood, an effect increased by infection with Plasmodium berghei.
      Parasitemia in P. berghei infected mice was significantly decreased (from 54% to
      33% of circulating erythrocytes 20 days after infection) and mouse survival
      significantly enhanced (from 0% to 20% 30 days after infection) in iron-deficient
      mice. In conclusion, iron deficiency favourably influences the course of malaria,
      an effect partially due to accelerated suicidal death and subsequent clearance of
      infected erythrocytes.

PMID- 17445764
TI  - Intein-mediated expression is an effective approach in the study of beta
      defensins.
AB  - Mammalian beta-defensins are an important family of host defense peptides with
      diverse functions. Surprisingly most of the mammalian beta-defensin genes are
      revealed preferentially expressed in the male organs. There is a pressing need to
      understand how the ample defensin repertoires work in both host defense and
      fertility with an aim to overcome antibiotic resistance of pathogens and
      reproductive problems. The biggest obstacle is the production of beta-defensin
      peptides as beta-defensins are small, antimicrobial and multi-disulfide
      molecules. In this study, the well documented HBD2, function-unknown RBD1 and
      function-partly-known rBin1b are successfully expressed and assayed. This
      approach overcomes the difficulties in beta-defensin production and provides a
      convenient and economical peptide-production platform to elucidate the
      antimicrobial activities and clinical prospects of beta-defensins. In the
      strategy of recombinant expression, this approach may be the best to develop the
      "natural" peptide pools for both host defense and fertility in a cost-effective
      manner.

PMID- 17445763
TI  - Phenobarbital suppresses vitamin D3 25-hydroxylase expression: a potential new
      mechanism for drug-induced osteomalacia.
AB  - Prolonged therapy with phenobarbital may cause vitamin D deficiency or
      osteomalacia. In the current study, we propose a novel mechanism for drug-induced
      osteomalacia involving impaired bioactivation of vitamin D(3) due to decreased 25
      hydroxylation of vitamin D(3) in liver. The present data, using the pig as model,
      demonstrate direct effects by phenobarbital on the expression of CYP27A1 and
      CYP2D25, two important 25-hydroxylases. Treatment by phenobarbital markedly
      reduced the rate of 25-hydroxylation by primary hepatocytes and suppressed the
      cellular CYP27A1 mRNA levels. The rate of 25-hydroxylation by two different
      purified 25-hydroxylases, microsomal CYP2D25, and mitochondrial CYP27A1,
      respectively, was dose-dependently inhibited by phenobarbital. Reporter assay
      experiments in liver-derived HepG2 cells revealed a marked PXR-mediated
      transcriptional downregulation of the CYP2D25 promoter. In addition, the data
      indicate that phenobarbital might affect the mRNA stability of CYP2D25. Taken
      together, the data suggest that vitamin D(3) 25-hydroxylation may be suppressed
      by phenobarbital. A downregulation of 25-hydroxylation by phenobarbital may
      explain, at least in part, the increased risk of osteomalacia, bone loss, and
      fractures in long-term phenobarbital therapy.

PMID- 17445765
TI  - Homeodomain transcription factor Hesx1/Rpx occupies Prop-1 activation sites in
      porcine follicle stimulating hormone (FSH) beta subunit promoter.
AB  - Homeodomain repressor factor Hesx1/Rpx plays a crucial role in the formation of
      Rathke's pouch at the start of pituitary organogenesis and represses the Prop-1
      dependent expression of Pit-1 gene, which promotes the differentiation of Pit-1
      dependent hormone producing cells. Recently, we discovered a novel function of
      Prop-1 by which it activates the porcine follicle stimulating hormone beta
      subunit (FSHbeta) gene through Fd2 region (-852/-746). The present study aimed to
      determine whether Hesx1 exerts its role in the Prop-1-dependent activation of
      FSHbeta gene. Transient transfection assay for the porcine FSHbeta promoter 
      985/+10, electrophoretic mobility shift assay (EMSA) and DNase I footprinting
      analysis for Fd2 region were carried out. Transfection assay in GH3 cells
      demonstrated that expression of Hesx1 alone does not change the promoter activity
      but the coexpression with Prop-1 represses the Prop-1-dependent activation of
      FSHbeta promoter. Similar results were obtained for the mutant reporter vector
      deleting the region -745/-104 indicating that Fd2 region is a target site of
      Hesx1 as well as Prop-1. EMSA and DNase I footprinting analysis using recombinant
      Hesx1 and Prop-1 protein demonstrated that Hesx1 and Prop-1 certainly bind to the
      AT-rich regions in a different manner. These results suggest that Hesx1 blocks
      the advanced expression of FSHbeta gene in the early stage of pituitary
      development, and Prop-1 thereafter appears and activates this gene.

PMID- 17445766
TI  - Coordinated expression of ncRNAs and HOX mRNAs in the human HOXA locus.
AB  - In the human HOXA locus a number of ncRNAs are transcribed from the intergenic
      regions in the opposite direction to HOXA mRNAs. We observed that the genomic
      organization of genes for the ncRNAs and HOXA proteins is highly conserved
      between human and mouse. We examined the expression profiles of these ncRNAs and
      HOXA mRNAs in various human tissues. The expression patterns of ncRNAs in human
      tissues coincide with those of the adjacent HOXA mRNAs that are collinearly
      expressed along the anteroposterior axis. This coordinated expression was
      observed even in transformed tumors and cancer cell lines, suggesting that the
      expression of ncRNAs is prerequisite for the regulated expression of HOXA genes.
      HIT18844 ncRNA transcribed from the most upstream position of the HOXA cluster
      possesses an ultra-conserved short stretch which potentially forms an
      evolutionarily conserved secondary structure. Our data suggest a critical role
      for ncRNAs in the regulation of HOXA gene expression.

PMID- 17445767
TI  - Liver-X-receptor activator prevents homocysteine-induced production of IgG
      antibodies from murine B lymphocytes via the ROS-NF-kappaB pathway.
AB  - Our previous study showed that homosysteine (Hcy) promotes proliferation of mouse
      splenic B lymphocytes. In this study, we investigated whether Hcy could stimulate
      the production of IgG antibodies. Hcy significantly increased the production of
      IgG antibodies from resting B lymphocytes. B lymphocytes from ApoE-knockout mice
      with hyperhomocysteinemia showed elevated IgG secretion at either the basal Hcy
      level or in response to lipopolysaccharide. Hcy promoted reactive oxygen species
      (ROS) formation, and free radical scavengers, MnTMPyP decreased Hcy-induced IgG
      secretion. The inhibitor of NF-kappaB (MG132) also significantly reduced Hcy
      induced IgG secretion. Furthermore, Hcy-induced formation of ROS, activation of
      NF-kappaB, and secretion of IgG could be inhibited by the liver-X-receptor (LXR)
      agonist T0901317. Thus, our data provide strong evidence that HHcy induces IgG
      production from murine splenic B lymphocytes both in vitro and in vivo. The
      mechanism might be through the ROS-NF-kappaB pathway and can be attenuated by the
      activation of LXR.

PMID- 17445768
TI  - An alternative transcript of the FOG-2 gene encodes a FOG-2 isoform lacking the
      FOG repression motif.
AB  - The FOG family of transcriptional co-factors is composed of two members in
      mammals: FOG-1 and FOG-2. Both have been shown to bind to GATA factors and
      function as transcriptional co-repressors in specific cell and promoter contexts.
      We have previously defined a novel repression domain localized to the N-terminus
      of each FOG family member, the FOG repression motif, which is necessary for FOG
      mediated transcriptional repression. In this report, we describe the
      identification and characterization of a novel isoform of FOG-2 lacking the FOG
      repression motif. In contrast to full-length FOG-2, this isoform is expressed
      predominately in the embryonic and adult heart. It can bind GATA4 avidly, but is
      unable to repress GATA4-mediated activation of cardiac-restricted gene promoters.
      Together, these results suggest that FOG-2 repressive activity may be modulated
      by the generation of isoforms of FOG-2 lacking the FOG repression motif.

PMID- 17445769
TI  - Mesenchymal stem cells modified with angiopoietin-1 improve remodeling in a rat
      model of acute myocardial infarction.
AB  - We used human angiopoietin-1 (hAng1)-modified mesenchymal stem cells (MSCs) to
      treat acute myocardial infarction (AMI) in rats. The hAng1 gene was transfected
      into cultured rat MSCs using an adenoviral vector. Five million hAng-transfected
      MSCs (MSC(Ang1)) or green fluorescent protein transfected MSCs (MSC(GFP)) or PBS
      only (PBS group) were injected intramyocardially into the inbred Lewis rat hearts
      immediately after myocardial infarction. MSC(Ang1) survived in the infarcted
      myocardium, and expressed hAng1 at both mRNA and protein levels. The vascular
      density was higher in the MSC(Ang1) and MSC(GFP) groups than in the PBS group.
      The measurements of infarcted ventricular wall thickness, infarction area, and
      left ventricular diameter indicated that heart remodeling was inhibited and heart
      function was improved in both the MSC(Ang1) and MSC(GFP) groups. However, in
      contrast to the MSC(GFP) group, the MSC(Ang1) group showed enhanced angiogenesis
      and arteriogenesis (by 11-35%), infarction area was reduced by 30% and the left
      ventricular wall was 46% thicker (P<0.05). The results indicated that hAng1
      modified MSCs improved heart function, followed by angiogenic effects in
      salvaging ischemic myocardium and reduced cardiac remodeling.

PMID- 17445770
TI  - Histone H2A mobility is regulated by its tails and acetylation of core histone
      tails.
AB  - Histone tail domains play important roles in cellular processes, such as
      replication, transcription, and chromosome condensation. Histone H2A has one
      central and two tail domains, and their functions have mainly been studied from a
      biochemical perspective. In addition, analyses based on visualization have been
      employed for functional analysis of some chromatin proteins. In this study, we
      analyzed histone H2A mobility in vivo by two-photon FRAP, and elucidated that the
      histone H2A N- and C-terminal tails regulate its mobility. We found that histone
      H2A mobility was increased following treatment of host cells with a histone
      deacetylase inhibitor. Our results support a model in which core histone tails
      directly regulate transcription by interacting with nucleosome DNA via
      electrostatic interactions.

PMID- 17445771
TI  - NF-kappaB regulates Lef1 gene expression in chondrocytes.
AB  - The relation of Wnt/beta-catenin signaling to osteoarthritis progression has been
      revealed with little information on the underlying molecular mechanism. In this
      study we found overexpression of Lef1 in cartilage tissue of osteoarthritic
      patients and elucidated molecular mechanism of NF-kappaB-mediated Lef1 gene
      regulation in chondrocytes. Treatment of IL-1beta augmented Lef1 upregulation and
      nuclear translocation of NF-kappaB in chondrocytes. Under IL-1beta signaling,
      treatment of NF-kappaB nuclear translocation inhibitor SN-50 reduced Lef1
      expression. A conserved NF-kappaB-binding site between mouse and human was
      selected through bioinformatic analysis and mapped at the 14 kb upstream of Lef1
      transcription initiation site. NF-kappaB binding to the site was confirmed by
      chromatin immunoprecipitation assay. Lef1 expression was synergistically
      upregulated by interactions of NF-kappaB with Lef1/beta-catenin in chondrocytes.
      Our results suggest a pivotal role of NF-kappaB in Lef1 expression in arthritic
      chondrocytes or cartilage degeneration.

PMID- 17445772
TI  - Involvement of the betaTrCP in the ubiquitination and stability of the HIV-1 Vpu
      protein.
AB  - The human immunodeficiency virus type 1 (HIV-1) Vpu protein binds to the CD4
      receptor and targets it to the proteasome for degradation. This process requires
      the recruitment of human betaTrCP, a component of the Skp1-Cullin-F box (SCF)
      ubiquitin ligase complex, that interacts with phosphorylated Vpu molecules. Vpu,
      unlike other ligands of betaTrCP, has never been reported to be degraded. We
      provide evidence that Vpu, itself, is ubiquitinated and targeted for degradation
      by the proteasome. We demonstrate that the mutant Vpu2.6, which cannot interact
      with betaTrCP, is stable and, unlike wild-type Vpu, is not polyubiquitinated.
      These results suggest that betaTrCP is involved in Vpu polyubiquitination.

PMID- 17445773
TI  - Short-hairpin RNA-mediated stable silencing of Grb2 impairs cell growth and DNA
      synthesis.
AB  - Grb2 is an SH2-SH3 protein adaptor responsible for linking growth factor
      receptors with intracellular signaling cascades. To study the role of Grb2 in
      cell growth, we have generated a new COS7 cell line (COS7(shGrb2)), based on RNAi
      technology, as null mutations in mammalian Grb2 genes are lethal in early
      development. This novel cell line continuously expresses a short hairpin RNA that
      targets endogenous Grb2. Stable COS7(shGrb2) cells had the shGrb2 integrated into
      the genomic DNA and carried on <10% of normal levels of Grb2. Silencing Grb2
      expression reduced, but did not eliminate, basal cell growth rate. This could be
      reversed by either the addition of neomycin to the cell cultures or by rescuing
      with an Xpress-Grb2(SiL) construct (made refractory to the shRNA-mediated
      interference), but not with an SH2-deficient mutant (R86K). Thus, a viable knock
      down and rescue protocol has demonstrated that Grb2 is crucial for cell
      proliferation.

PMID- 17445774
TI  - Studies of the in vitro Nalpha-acetyltransferase activities of E. coli RimL
      protein.
AB  - Although the Escherichia coli N(alpha)-acetyltransferase RimL catalyzing the N
      terminal acetylation of L12 have been identified through mutant analysis, little
      is known about its enzymatic activity and auxiliary subunit requirement. This
      study was to investigate the enzymatic activities of RimL and its substrate
      specificity. RimL, its substrate L12, and two mutant substrates L12S1A and L12I2D
      were overexpressed and purified from E. coli. In vitro experimental results
      revealed that RimL itself can convert L12 to L7 by acetylation of the N-terminal
      serine residue. The K(m) value for L12 was 0.55 microM and the V(max) was 25.71
      min(-1) as determined by a spectrophotometrical method. We also found that RimL
      acetylated the L12S1A mutant with an N-terminal alanine residue instead of the
      native serine residue, suggesting RimL can acetylate other N-terminal residues.
      Furthermore, when the second N-terminal residue isoleucine was replaced by
      aspartic acid, the mutant L12I2D was also acetylated by RimL but under a much
      lower rate.

PMID- 17445775
TI  - Multidrug-resistant cancer cells are preferential targets of the new
      antineoplastic lanthanum compound KP772 (FFC24).
AB  - Recently, we have introduced [tris(1,10-phenanthroline)lanthanum(III)]
      trithiocyanate (KP772, FFC24) as a new lanthanum compound which has promising
      anticancer properties in vivo and in vitro. Aim of this study was to investigate
      the impact of ABC transporter-mediated multidrug resistance (MDR) on the
      anticancer activity of KP772. Here, we demonstrate that all MDR cell models
      investigated, overexpressing ABCB1 (P-glycoprotein), ABCC1 (multidrug resistance
      protein 1), or ABCG2 (breast cancer resistance protein) either due to drug
      selection or gene transfection, were significantly hypersensitive against KP772.
      Using ABCB1-overexpressing KBC-1 cells as MDR model, KP772 hypersensitivity was
      demonstrated to be based on stronger apoptosis induction and/or cell cycle arrest
      at unaltered cellular drug accumulation. KP772 did neither stimulate ABCB1 ATPase
      activity nor alter rhodamine 123 accumulation arguing against a direct
      interaction with ABCB1. Accordingly, several drug resistance modulators did not
      sensitize but rather protect MDR cells against KP772-induced cytotoxicity.
      Moreover, long-term KP772 treatment of KBC-1 cells at subtoxic concentrations led
      within 20 passages to a complete loss of drug resistance based on blocked MDR1
      gene expression. When exposing parental KB-3-1 cells to subtoxic, stepwise
      increasing KP772 concentrations, we observed, in contrast to several other
      metallo-drugs, no acquisition of KP772 resistance. Summarizing, our data
      demonstrate that KP772 is hyperactive in MDR cells and might have
      chemosensitizing properties by blocking ABCB1 expression. Together with the
      disability of tumor cells to acquire KP772 resistance, our data suggest that
      KP772 should be especially active against notoriously drug-resistant tumor types
      and as second line treatment after standard chemotherapy failure.

PMID- 17445776
TI  - A synthetic analog of alpha-galactosylceramide induces macrophage activation via
      the TLR4-signaling pathways.
AB  - Alpha-galactosylceramide (alpha-GalCer), a bioactive glycolipid isolated from the
      marine sponge Agelas mauritianus, is a potent immunomodulator with therapeutic
      potential for the treatment of autoimmune diseases and cancer. The Toll-like
      receptor 4 (TLR4), one of the promising molecular targets for immune-modulating
      drugs, is commonly expressed in innate immune cells especially macrophages and
      dendritic cells. Currently, whether alpha-GalCer can activate TLR4 signaling
      pathways remains unreported. In this study, we examined the effects of alpha
      GalCer and its various structural analogs, CCL-1 approximately 47, on TLR4
      activation. We found that one alpha-GalCer analog (CCL-34), but not alpha-GalCer
      itself, strongly stimulated NF-kappaB activity in RAW 264.7 cells. CCL-34
      activated NF-kappaB in a TLR4-dependent manner and stimulated TNF-alpha
      production in bone marrow cells of TLR4-functional C3H/HeN mice but not in those
      of TLR4-defective C3H/HeJ mice. Furthermore, CCL-34 treatment stimulated NF
      kappaB activation and IL-8 production in a 293 cell line constitutively
      expressing human TLR4, MD-2 and CD14. Treatment of RAW 264.7 cells with CCL-34
      also activated TLR4-downstream mitogen-activated protein kinases (ERK, JNK and
      p38), induced expression of TLR4-downstream genes (TNF-alpha, IL-6, IL-1beta and
      iNOS) and promoted production of cytokines characteristic of activated
      macrophages. CCL-34-treated RAW 264.7 cells acquired a distinct morphology
      similar to that of LPS-activated macrophages and exhibited higher phagocytotic
      activity. Moreover, treatment with a TLR4-neutalizing antibody inhibited the CCL
      34-induced morphological alteration. In summary, we identify a novel synthetic
      compound CCL-34 that can activate macrophages via TLR4-dependent signaling
      pathways. Our results suggest that CCL-34 is an immune modulator and may serve as
      a potential drug lead for immunotherapy.

PMID- 17445777
TI  - Oxidative DNA base damage in MCF-10A breast epithelial cells at clinically
      achievable concentrations of doxorubicin.
AB  - The cellular metabolism of doxorubicin generates reactive oxygen species with
      significant potential to damage DNA. Such DNA damage can result in mutations if
      not adequately repaired by cellular DNA repair pathways. Secondary malignancies
      have been reported in patients who have received doxorubicin-containing
      chemotherapeutic regimens; however, the underlying molecular mechanism(s) to
      explain the development of these tumors remains under active investigation. We
      have previously demonstrated the presence of DNA bases modified by oxidation in
      the peripheral blood mononuclear cells of patients with breast cancer following
      treatment with doxorubicin. In those studies, doxorubicin was administered by
      continuous infusion over 96 h to minimize the risk of cardiac toxicity. To
      evaluate potential mechanisms underlying doxorubicin-induced DNA base oxidation
      in non-malignant tissues, MCF-10A breast epithelial cells were cultured for 96 h
      with the same doxorubicin concentration achieved in vivo (0.1 microM). During
      doxorubicin exposure, MCF-10A cells underwent growth arrest and apoptosis,
      developed elevated levels of reactive oxygen species, and demonstrated a time
      dependent and significant increase in the levels of 11 oxidized DNA bases, as
      determined by gas chromatography/mass spectroscopy. Diminished expression of DNA
      repair enzymes was also observed over the same time course. Thus, clinically
      achievable concentrations of doxorubicin induce a level of oxidative stress in
      MCF-10A cells that is capable of oxidizing DNA bases and significantly altering
      cellular proliferation.

PMID- 17445778
TI  - Cannabinoids inhibit sodium-dependent, high-affinity excitatory amino acid
      transport in cultured rat cortical astrocytes.
AB  - Cannabinoids have been shown to increase the extracellular levels of glutamate in
      vivo and in vitro, but no studies have evaluated the possible involvement of
      glial glutamate reuptake system. The present study investigates whether
      cannabinoids and endocannabinoid, anandamide have an effect on astroglial
      excitatory amino acid (EAA) transport. The kinetics of glutamate transport was
      studied in rat cortical astrocytes, using the radiolabeled, non-metabolized amino
      acid, D-[3H] aspartate in the absence or presence of cannabinoid receptor
      agonists. The results show that in vehicle controls the uptake of d-aspartate was
      rapid, sodium-dependent and saturated within the first 5 min, resulting in a K(m)
      7.365+/-1.16 micromol/L (n=5) and the maximum velocity (V(max)) 1207+/-51 nmol/mg
      protein/min. Addition of the synthetic cannabinoid analog R(+)-[2,3-dihydro-5
      methyl-3-[(morpholinyl)methyl]pyrrolol][1,2,3de]-1,4-benzoxazinyl]-(1
      naphthalenyl)methanone (WIN 55,212-2; 3 micromol/L) increased the K(m) (26.25+/
      4.84 micromol/L) without affecting the V(max) (1122+/-77 nmol/mg protein/min),
      suggesting the inhibition was competitive and reversible. Various other
      cannabinoid agonists also inhibited D-aspartate uptake in a dose-dependent and
      stereospecific manner. The cannabinoid inhibition of EAA transport was partially
      blocked by the cannabinoid type-1 (CB1) receptor antagonist N-(piperidin-1-yl-5(4
      chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3
      carboxamidehydrochloride (SR141716A; 100 nmol/L). The inhibitory effects of WIN
      55,212-2, or its endogenous counterpart anandamide were reversed by 98,059, an
      inhibitor of mitogen-activated kinase (MAPK) kinase (MEK). These results suggest
      that cannabinoids and endocannabinoids may constitute a novel class of inhibitors
      of astroglial glutamate transport system.

PMID- 17445779
TI  - Enhancement of cisplatin induced apoptosis by suberoylanilide hydroxamic acid in
      human oral squamous cell carcinoma cell lines.
AB  - Both the resistance of tumor cells to cisplatin and dose-related toxicity remain
      two of the most important problems in the chemotherapy of clinical oral squamous
      cell carcinoma (OSCC). Researchers have been seeking a combinative treatment
      regimen to improve the effect of chemotherapy. As potent new anti-cancer drugs,
      histone deacetylase inhibitors (HDACI(S)) have been reported to be associated
      with chromatin modification and display synergistic activities with some
      traditional chemotherapeutic agents. In this study, we evaluated the potential
      combinative effect of low dose cisplatin and suberoylanilide hydroxamic acid
      (SAHA, one of the most potent HDACI(S)) in OSCC cell lines. Cell viability and
      apoptotic assay were examined. Compared with either cisplatin (4 microg/ml) or
      SAHA (2 microM) treated alone, co-administration of both drugs synergistically
      induces cytotoxicity and apoptosis in both Tca8113 and KB cell lines.
      Furthermore, diverse apoptosis-associated proteins, including p53, BID,
      cytochrome C and caspase-3 were involved in the induction of apoptosis. Our
      results suggest that concurrent treatment with SAHA enhances tumor cell
      sensitivity to subtoxic doses of cisplatin. This may be regarded as a novel
      strategy for treatment of OSCC.

PMID- 17445780
TI  - Specific blockage of ligand-induced degradation of the Ah receptor by proteasome
      but not calpain inhibitors in cell culture lines from different species.
AB  - To firmly establish the pathway involved in ligand-induced degradation of the
      AHR, cell lines derived from mouse rat or human tissues were exposed to
      inhibitors specific to the proteasome or calpain proteases and exposed to TCDD.
      The level of endogenous AHR and CYP1A1 protein was then evaluated by quantitative
      Western blotting. Treatment of cells with the calpain inhibitors: calpeptin,
      calpain inhibitor III, or PD150606 either individually or in combinations up to
      75 microM did not reduce TCDD-induced degradation of the AHR, the induction of
      endogenous CYP1A1 or the nuclear accumulation of the AHR. The activity of the
      inhibitors was verified with an in vivo calpain assay. In contrast, exposure of
      cells to the specific proteasome inhibitors: epoxomicin (1-5 microM), proteasome
      inhibitor I (5-10 microM) or lactacystin (5-15 microM) completely inhibited TCDD
      induced degradation of the AHR. Inhibition of AHR degradation with these
      compounds did not reduce the induction of endogenous CYP1A1. In addition,
      exposure of the Hepa-1 line to the various proteasome inhibitors caused an
      accumulation of the AHR in the nucleus in the absence of TCDD exposure. Finally,
      Western blot analysis of the DNA bound AHR showed that its molecular mass was
      unchanged in comparison to the unliganded (cytoplasmic) AHR. Thus, these studies
      conclusively implicate the proteasome and not calpain proteases in the ligand
      induced degradation of the mouse, rat and human AHR and suggest that the
      pharmacological use of proteasome inhibitors may impact the time course and
      magnitude of gene regulatory events mediated through the AHR.

PMID- 17445781
TI  - N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological
      gambling: a pilot study.
AB  - BACKGROUND: Although pathological gambling (PG) is relatively common,
      pharmacotherapy research for PG is limited. N-acetyl cysteine (NAC), an amino
      acid, seems to restore extracellular glutamate concentration in the nucleus
      accumbens and therefore offers promise in reducing addictive behavior. METHODS:
      Twenty-seven subjects (12 women) with DSM-IV PG were treated in an 8-week open
      label trial of NAC with responders (defined as a > or = 30% reduction in Yale
      Brown Obsessive Compulsive Scale Modified for Pathological Gambling [PG-YBOCS]
      total score at end point) randomized to 6 weeks of double-blind NAC or placebo.
      RESULTS: The PG-YBOCS scores decreased from a mean of 20.3 +/- 4.1 at baseline to
      11.8 +/- 9.8 at the end of the open-label phase (p < .001). Sixteen of 27
      subjects (59.3%) met responder criteria. The mean effective dose of NAC was
      1476.9 +/- 311.3 mg/day. Of 16 responders, 13 entered the double-blind phase. Of
      those assigned to NAC, 83.3% still met responder criteria at the end of the
      double-blind phase, compared with only 28.6% of those assigned to placebo.
      CONCLUSIONS: The efficacy of NAC lends support to the hypothesis that
      pharmacological manipulation of the glutamate system might target core symptoms
      of reward-seeking addictive behaviors such as gambling. Larger, longer, placebo
      controlled double-blind studies are warranted.

PMID- 17445782
TI  - Reduced central c-fos expression and febrile response to repeated LPS injection
      into periodontal tissue of rats.
AB  - Systemic injection of repeated doses of Escherichia coli lipopolysaccharide (LPS)
      results in attenuation of the febrile response, i.e. endotoxin tolerance, which
      has been fairly well characterized in rats. In the present study, we tested the
      hypothesis that endotoxin tolerance also occurs after repeated local injection of
      LPS into periodontal protection tissue. Male Wistar rats were given a gingival
      intra-pouch injection of sterile saline or LPS at dose of 100 microg/kg on three
      consecutive days. Body core temperature (Tb) was measured with a miniature
      datalogger. Another group of animals were used for Fos immunohistochemistry 3 h
      after the injections in both non-tolerant and tolerant animals. On day one we
      observed a polyphasic febrile response after LPS injection. The increase in body
      temperature started about 2 h after LPS administration and lasted 5 h. On day two
      this response was sensitized and on day three the febrile response was completely
      abolished. These data suggest that rats develop endotoxin tolerance after
      repeated LPS administrations into tissues within the oral cavity. Moreover,
      immunohistochemistry detected a reduction in LPS-induced Fos-like
      immunoreactivity expression in the subnucleus caudalis of spinal trigeminal
      nucleus and in the preoptic area of the hypothalamus (POA) in tolerant rats
      compared with non-tolerant animals, indicating that the endotoxin tolerance may
      be locally mediated in the periodontal protection tissues of rats.

PMID- 17445783
TI  - When emotional prosody and semantics dance cheek to cheek: ERP evidence.
AB  - To communicate emotionally entails that a listener understands a verbal message
      but also the emotional prosody going along with it. So far the time course and
      interaction of these emotional 'channels' is still poorly understood. The current
      set of event-related brain potential (ERP) experiments investigated both the
      interactive time course of emotional prosody with semantics and of emotional
      prosody independent of emotional semantics using a cross-splicing method. In a
      probe verification task (Experiment 1) prosodic expectancy violations elicited a
      positivity, while a combined prosodic-semantic expectancy violation elicited a
      negativity. Comparable ERP results were obtained in an emotional prosodic
      categorization task (Experiment 2). The present data support different ERP
      responses with distinct time courses and topographies elicited as a function of
      prosodic expectancy and combined prosodic-semantic expectancy during emotional
      prosodic processing and combined emotional prosody/emotional semantic processing.
      These differences suggest that the interaction of more than one emotional channel
      facilitates subtle transitions in an emotional sentence context.

PMID- 17445784
TI  - B3LYP/6-311++G* * study of structure and spin-spin coupling constant in heparin
      disaccharide.
AB  - Structures of heparin disaccharide have been analyzed by DFT using the B3LYP/6
      311++G( * *) method. The optimized geometries of two forms of this disaccharide,
      differing in the conformation ((1)C(4) and (2)S(0)) of the IdoA2S residue,
      confirmed considerable influences of the sulfate and the carboxylate groups upon
      the pyranose ring geometries. The computed energies showed that disaccharide
      having the (1)C(4) form of the IdoA2S residue is more stable than that with the
      (2)S(0) form. Interatomic distances, bond and torsion angles showed that
      interconversion of the IdoA2S residue results in geometry changes in the GlcN,6S
      residue as well. Three-bond proton-proton and proton-carbon spin-spin coupling
      constants computed for both forms agree with the experimental data and indicate
      that only two chair forms contribute to the conformational equilibrium in
      disaccharide. Influences of the charged groups upon the magnitudes of spin-spin
      coupling constants are also discussed.

PMID- 17445785
TI  - Crystallization kinetics of amorphous lactose, whey-permeate and whey powders.
AB  - Amorphous lactose, whey-permeate and whey powders have been converted to their
      crystalline forms by exposure to air at various temperatures and relative
      humidities. The total time required for sorption, induction and crystallization
      of these powders was observed by following the time-dependent mass change of the
      powders during treatment. These experiments have shown that higher temperatures
      and relative humidities lead to shorter crystallization times. Lactose
      crystallizes within 1 min at an air temperature of 100 degrees C and relative air
      humidity of 80%, whereas whey-permeate and whey powders requires up to 5 min at
      the same set of conditions. Thus, as previously described, the presence of
      proteins and salts in the whey-permeate and whey powders reduces the
      crystallization rate. The rate constants and activation energies have been
      determined over a range of temperatures and humidities to enable the calculation
      of crystallization times for the design of an industrial process that
      crystallizes whey and whey-permeate powders. Finally, the crystallization rates
      found in this work are sufficiently fast to be applicable in an industrial
      process that crystallizes whey and whey-permeate powders.

PMID- 17445786
TI  - Spectrophotometric evidence for the formation of short-lived hypomanganate(V) and
      manganate(VI) transient species during the oxidation of K-carrageenan by alkaline
      permanganate.
AB  - Spectrophotometric detection of the formation of short-lived hypomanganate(V),
      [KCAR-Mn(V)O43-], and manganate(VI), [KCAR-Mn(VI)O42-], intermediates has been
      confirmed through the oxidation of K-carrageenan (KCAR) by potassium permanganate
      in alkaline solutions of pH's >or= 12 using a conventional spectrophotometer. The
      short-lived transient species were characterized and a mechanism consistent with
      experimental observations is suggested.

PMID- 17445787
TI  - Evolutionary deimmunization: an ancillary mechanism for self-tolerance?
AB  - Self-proteins in the extracellular environment are constantly sampled and
      processed through the Class II antigen presentation pathway. Mechanisms
      responsible for central and peripheral tolerance reduce the chance of autoimmune
      responses to these proteins. However, tolerance can and does break down, leading
      to the development of autoimmune disease. In a preliminary analysis, we observed
      that common serum proteins have fewer HLA class II-restricted T-cell epitopes
      than expected, when compared to random protein sequences. We therefore performed
      a broader analysis of human proteins to determine whether the number of T-cell
      epitopes in extracellular proteins is reduced in comparison with non-secreted
      (intracellular) proteins. Here we document fewer putative HLA class II-restricted
      T-cell epitopes in extracellular proteins, compared to intracellular proteins.
      These data suggest that the diminished presence of T-cell epitopes may reduce the
      potential for autoimmunity. Over evolutionary timescales, immune pressure may
      have resulted in alterations in the inherent T-cell immunogenic potential of
      autologous proteins.

PMID- 17445788
TI  - Numerical revelation of the kinetic significance of individual steps in the
      reaction mechanism of methyl linoleate peroxidation inhibited by alpha
      tocopherol.
AB  - A kinetic model was constructed to describe the reactions involved in the
      oxidation of methyl linoleate (ML) inhibited by alpha-tocopherol (TH). The
      initial model of the reaction mechanism included 53 individual steps, which were
      numerically analyzed by the value method based on Hamiltonian systematization of
      kinetic equations. Good accord was obtained with experimental data at 40 and 50
      degrees C. The dominant steps responsible for the antioxidant and pro-oxidant
      properties of TH in the process of ML peroxidation were revealed. Tocopherol
      mediated peroxidation (TMP) and generation of alkoxyl radicals as a result of the
      reduction of hydroperoxides by TH or the decomposition tocopherol alkyl peroxides
      are the dominant reactions responsible for the pro-oxidant activities of alpha
      tocopherol. The extreme behavior of reaction induction period in relation to TH
      initial concentration is related to the increase in the ratios of [tocopheroxyl
      radical]/[peroxyl radical] and the TMP rate/rate of termination by combination of
      tocopheroxyl and peroxyl radicals.

PMID- 17445789
TI  - Hemoglobin and N-terminal pro-brain natriuretic peptide: Independent and
      synergistic predictors of mortality in patients with acute heart failure Results
      from the International Collaborative of NT-proBNP (ICON) Study.
AB  - BACKGROUND: Hemoglobin and amino-terminal pro-brain natriuretic peptide (NT
      proBNP) are both independent predictors of mortality in patients with chronic HF.
      Their combined predictive power for mortality in the setting of acute HF is
      uncertain. METHODS: In an international prospective cohort design, we evaluated
      the relationships between hemoglobin, NT-proBNP, and 60-day mortality in 690
      patients with acute HF. RESULTS: The median hemoglobin for the entire cohort was
      13.0 g/dL (interquartile range 11.6-14.3). The WHO criterion for anemia was met
      by 44% (n=305). The 60-day mortality rate for anemic patients was 16.4% vs. 8.8%
      in non-anemic patients (p<0.001). Anemia was an independent predictor of short
      term mortality (OR=1.72, 95% CI=1.05-2.80, p=0.03), as was a NT-proBNP
      concentration >5180 pg/mL (OR=2.32, 95% CI=1.36-3.94 p=0.002). Consideration of
      four risk groups: not anemic/low NT-proBNP (reference group, n=220), anemic/low
      NT-proBNP (n=152), not anemic/high NT-proBNP (n=165), and anemic/high NT-proBNP
      (n=153) revealed respective 60-day mortality rates of 5.0% (referent), 9.2%
      (OR=1.93, 95% CI=0.85-4.36; p=0.12), 13.9% (OR=3.07, 95% CI=1.45-6.50, p=0.003),
      and 23.5% (OR=5.84, 95% CI=2.87-11.89, p<0.001). CONCLUSIONS: Anemia was common
      in this cohort of subjects with acute HF and was related to adverse short-term
      outcome. Integrated use of hemoglobin and NT-proBNP measurements provides
      powerful additive information and is superior to the use of either in isolation.

PMID- 17445790
TI  - Anaphoric agreement violation: an ERP analysis of its interpretation.
AB  - In the present study we analyzed the processing of grammatically anomalous
      sentences like "The famous dancer were nervously preparing herself/themselves to
      face the crowd.", which contains two anomalies, one early and one late. We
      investigated how processing of the later anomaly (at the pronoun 'herself' or
      'themselves') was affected by the processing of the early anomaly (at 'were'). We
      considered two processing scenarios involving the first anomaly: (1) The
      representation of the subject-verb number agreement error at the first verb is
      coerced to match the verb, rendering 'herself' anomalous; (2) The representation
      of the subject-verb agreement error is coerced to match the subject noun,
      rendering 'themselves' anomalous. Our dependent measure was event-related scalp
      potentials (ERPs). When the pronoun disagreed with the verb (and agreed with the
      subject), a P600 was recorded, while the opposite condition elicited no reliable
      effect. Our data suggest that interpretation of reflexive pronouns involves the
      reactivation of multiple lexical items, verbs included.

PMID- 17445791
TI  - The cognitive locus of distraction by acoustic novelty in the cross-modal oddball
      task.
AB  - Unexpected stimuli are often able to distract us away from a task at hand. The
      present study seeks to explore some of the mechanisms underpinning this
      phenomenon. Studies of involuntary attention capture using the oddball task have
      repeatedly shown that infrequent auditory changes in a series of otherwise
      repeating sounds trigger an automatic response to the novel or deviant stimulus.
      This attention capture has been shown to disrupt participants' behavioral
      performance in a primary task, even when distractors and targets are asynchronous
      and presented in distinct sensory modalities. This distraction effect is
      generally considered as a by-product of the capture of attention by the novel or
      deviant stimulus, but the exact cognitive locus of this effect and the interplay
      between attention capture and target processing has remained relatively ignored.
      The present study reports three behavioral experiments using a cross-modal
      oddball task to examine whether the distraction triggered by auditory novelty
      affects the processing of the target stimuli. Our results showed that variations
      in the demands placed on the visual analysis (Experiment 1) or categorical
      processing of the target (Experiment 2) did not impact on distraction. Instead,
      the cancellation of distraction by the presentation of an irrelevant visual
      stimulus presented immediately before the visual target (Experiment 3) suggested
      that distraction originated in the shifts of attention occurring between
      attention capture and the onset of the target processing. Possible accounts of
      these shifts are discussed.

PMID- 17445792
TI  - A study of the relationships between Parkinson's disease and markers of traffic
      derived and environmental manganese air pollution in two Canadian cities.
AB  - There is concern that industrial emissions of manganese (Mn) and the use of Mn
      containing compounds as fuel additives might increase the population risk of
      Parkinson's disease (PD)-like disorders. We investigated associations between the
      diagnosis and treatment of PD and markers of exposure to vehicle exhaust and
      industrial emissions of Mn within a cohort of 110,000 subjects in the cities of
      Toronto and Hamilton, Canada. Methylcyclopentadienyl manganese tricarbonyl (MMT)
      has been added to Canadian gasoline since 1976 and steelmaking in Hamilton emits
      Mn to the air. Using residential postal codes, subjects were mapped to: (1)
      residence locations close to traffic and to neighbourhood levels of NO2, as
      markers of traffic-generated air pollution (TGAP); and, (2) neighbourhood levels
      of ambient Mn in Hamilton, as measured by the Mn fraction of total suspended
      particulate. Subjects were linked to Ministry of Health administrative databases,
      1992-1999, to identify physicians' diagnoses of PD and prescriptions for l-Dopa
      containing medications. In Toronto, we found no association between PD and the
      markers of TGAP. In Hamilton, the odds ratio for a physician's diagnosis of PD
      was 1.034 (1.00-1.07) per 10 ng/m3 increase in Mn in TSP. The estimate of the
      "doubling exposure" for physician-diagnosed PD was about 150 ng/m3 Mn in TSP.
      Examination of prevalence curves suggested that exposure to ambient Mn advances
      the age of diagnosis of PD, consistent with the theory that exposure to Mn adds
      to the natural loss of neurons attributable to the aging process.

PMID- 17445793
TI  - Synthesis of long-term nickel monitoring in San Francisco Bay.
AB  - The Regional Monitoring Program for Water Quality in the San Francisco Bay (RMP)
      has conducted annual monitoring of the San Francisco Estuary (estuary) since
      1993. The RMP primarily monitors water, sediment, and bivalves, although short
      term pilot and special studies on select topics are also conducted. The purpose
      of this article is to synthesize over 10 years of RMP nickel data and to
      illustrate how comprehensive monitoring data contribute to an understanding of
      contaminant fate. Nickel concentrations observed in water (43.7-233.7 nM) are
      largely a function of the geology of the watershed surrounding the estuary and
      inputs from wastewater treatment plants and urban runoff. The geologic formations
      supplying sediment to the estuary contain high concentrations of nickel (e.g.,
      1000-3300 microg/g). Much of the research to date on nickel speciation suggests
      that nickel complexes from wastewater treatment plants are not readily available
      for biological uptake [Bedsworth, W.W., Sedlak, D.L., 1999. Sources and
      environmental fate of strongly complexed nickel in estuarine waters: the role of
      ethylenediaminetetraacetate. Environ. Sci. Technol. 33, 926-931, Sedlak, D.L.,
      Phinney, J.T., Bedsworth, W.W., 1997. Strongly complexed Cu and Ni in wastewater
      effluents and surface runoff. Environ. Sci. Technol. 31(10), 3010-3016, Donat,
      J.R., Lao, K.A., Bruland, K.W., 1994. Speciation of dissolved copper and nickel
      in South San Francisco Bay: a multi-method approach. Anal. Chim. Acta. 284, 547
      571]. In addition, concentrations of nickel measured in biota by the RMP (0.905
      113.0 microg/g dry weight in bivalve tissues) are well below recommended maximum
      tissue residue levels (220 microg/g wet weight, California state guidelines).
      Based on this information, regulators have reconsidered the water quality
      objectives developed for nickel.

PMID- 17445794
TI  - Endothelin-1 decreases [Ca2+]i via Na+/Ca2+ exchanger in CHO cells stably
      expressing endothelin ETA receptor.
AB  - Endothelin ET(A) receptor couples to Gq/11 protein that transduces a variety of
      receptor signals to modulate diverse cellular responses including Ca2+
      mobilization. Stimulation of endothelin ETA receptor with endothelin-1 is
      generally believed to induce an increase in intracellular Ca2+ concentration
      ([Ca2+]i) via Gq/11 protein. Here we provide the first convincing evidence that
      endothelin-1 elicited Gq/11 protein-dependent and -independent 'decrease' in
      [Ca2+]i via Na+/Ca2+ exchanger (NCX) in Chinese hamster ovary (CHO) cells stably
      expressing human endothelin ETA receptor. In the cells treated with 1 microM
      thapsigargin, an inhibitor of endoplasmic Ca2+ pump, that induces an increase in
      [Ca2+]i via capacitative Ca2+ entry, endothelin-1 induced a decrease in [Ca2+]i
      which was partially inhibited by YM-254890, a specific inhibitor of Gq/11,
      indicating that Gq/11-dependent and independent pathways are involved in the
      decrease. The endothelin-1-induced decrease in [Ca2+]i was markedly suppressed by
      3',4'-dichlorobenzamil hydrochloride, a potent NCX inhibitor, and also by a
      replacement of extracellular Na+ with Li+, which was not transported by NCX,
      indicating a major role of NCX operating in the forward mode in the endothelin-1
      induced decrease in [Ca2+]i. Molecular approach with RT-PCR demonstrated the
      expression of mRNA for NCX1, NCX2 and NCX3. These results suggest that
      stimulation of endothelin ETA receptor with endothelin-1 activates the forward
      mode NCX through Gq/11-dependent and -independent mechanisms: the NCX exports
      Ca2+ out of the cell depending on Na+ gradient across the cell membrane,
      resulting in the decrease in [Ca2+]i.

PMID- 17445795
TI  - Evidence for imidazoline receptors involvement in the agmatine antidepressant
      like effect in the forced swimming test.
AB  - This study investigated the involvement of the imidazoline receptors in the
      antidepressant-like effect of agmatine in the forced swimming test. The
      antidepressant-like effects of agmatine (10 mg/kg, i.p.) in the forced swimming
      test was blocked by pretreatment of mice with efaroxan (1 mg/kg, i.p., an
      imidazoline I1/alpha2-adrenoceptor antagonist), idazoxan (0.06 mg/kg, i.p., an
      imidazoline I2/alpha2-adrenoceptor antagonist) and antazoline (5 mg/kg, i.p., a
      ligand with high affinity for the I2 receptor). A subeffective dose of agmatine
      (0.001 mg/kg, i.p.) produced a synergistic antidepressant-like effect with
      clonidine (0.06 mg/kg, i.p, an imidazoline I1/alpha2-adrenoceptor agonist),
      moxonidine (0.5 mg/kg, i.p., an imidazoline I1/alpha2-adrenoceptor agonist),
      antazoline (1 mg/kg, i.p.) and MK-801 (0.001 mg/kg, i.p., a non-competitive NMDA
      receptor antagonist), but not with efaroxan (1 mg/kg, i.p.) and idazoxan (0.06
      mg/kg, i.p.). Pretreatment of mice with yohimbine (1 mg/kg, i.p., an alpha2
      adrenoceptor antagonist) blocked the synergistic antidepressant-like effect of
      agmatine (0.001 mg/kg, i.p.) with clonidine (0.06 mg/kg, i.p). A subeffective
      dose of MK-801 (0.001 mg/kg, i.p.) produced a synergistic antidepressant-like
      effect with antazoline (5 mg/kg, i.p.), but not with efaroxan (1 mg/kg, i.p.) or
      idazoxan (0.06 mg/kg, i.p.). In conclusion, this study suggests that the anti
      immobility effect of agmatine in the forced swimming test is dependent on its
      interaction with imidazoline I1 and I2 receptors.

PMID- 17445796
TI  - Cardiac effects of L/N-type Ca2+ channel blocker cilnidipine in anesthetized
      dogs.
AB  - Cardiac effects of L/N-type Ca2+ channel blocker cilnidipine were assessed using
      the halothane-anesthetized canine model. Cilnidipine (1 and 3 microg/kg, i.v.)
      lowered the mean blood pressure by -5 and -14 mm Hg, respectively, without
      affecting the heart rate or maximum upstroke velocity of left ventricular
      pressure. Isoproterenol or acetylcholine was intravenously injected to directly
      or indirectly induce the positive chronotropic responses, respectively.
      Cilnidipine hardly affected the isoproterenol-induced cardiac responses, but it
      attenuated the acetylcholine-induced reflex tachycardia to 63-78% of the pre-drug
      control level. These results suggest that clinically relevant doses of
      cilnidipine can directly attenuate the sympathetic tone.

PMID- 17445797
TI  - Involvement of GABA A receptor-associated chloride channels in the peripheral
      antinociceptive effect induced by GABA A receptor agonist muscimol.
AB  - The effect of chloride and potassium channel blockers on the antinociception
      induced by GABA(A) receptor agonist muscimol was investigated using the paw
      pressure test. Muscimol (1, 2, 4, 8 ng/paw) elicited a peripheral antinociceptive
      effect that was antagonized by bicuculline (10, 20, 40, 80 ng/paw), suggesting a
      specific effect. The muscimol effect was reverted by the chloride channel coupled
      GABA(A) receptor blocker, picrotoxin (0.4, 0.6, 0.8, 2 microg/paw). Potassium
      channel blockers did not modify the peripheral antinociception induced by
      muscimol. This study provides evidence that the peripheral antinociceptive effect
      of muscimol results from the activation of GABA(A) receptor-associated chloride
      channels.

PMID- 17445798
TI  - Characterization of the antiparkinsonian effects of the new adenosine A2A
      receptor antagonist ST1535: acute and subchronic studies in rats.
AB  - Antagonism of adenosine A2A receptor function has been proposed as an effective
      therapy in the treatment of Parkinson's disease. Thus, the study of new adenosine
      receptor antagonists is of great importance for the potential use of these drugs
      in clinical practice. The present study evaluated effects of the new preferential
      adenosine A2A receptor antagonist 2-butyl-9-methyl-8-(2H-1,2,3-triazol-2-yl)-9H
      purin-6-ylamine (ST1535) in unilaterally 6-hydroxydopamine lesioned rats. Acute
      ST1535 dose-dependently potentiated contralateral turning behaviour induced by a
      threshold dose of l-3,4-dihydroxyphenylalanine (L-DOPA) (3 mg/kg i.p.), a
      classical test for antiparkinson drug screening. Subchronic (18 days, twice a
      day) ST1535 (20 mg/kg i.p.)+L-DOPA (3 mg/kg i.p.) did not induce sensitization to
      turning behaviour or abnormal involuntary movements during the course of
      treatment, indicating a low dyskinetic potential of the drug. Moreover, while
      subchronic administration of a fully effective dose of L-DOPA (6 mg/kg i.p.)
      significantly increased GABA synthesizing enzyme glutamic acid decardoxylase
      (GAD67), dynorphin and enkephalin mRNA levels in the lesioned striatum,
      subchronic ST1535 (20 mg/kg i.p.)+L-DOPA (3 mg/kg i.p.) did not modify any of
      these markers, although it induced a similar number of contralateral rotations at
      the beginning of treatment. Finally, acute administration of ST1535 (20 mg/kg
      i.p.) proved capable of reducing jaw tremors in tacrine model of Parkinson's
      disease tremor. Results showed that ST1535, in association with a low dose of L
      DOPA, displayed antiparkinsonian activity similar to that produced by a full dose
      of L-DOPA without exacerbating abnormal motor side effects. Moreover, in
      agreement to other well characterized adenosine A2A receptor antagonists, ST1535
      features antitremorigenic effects.

PMID- 17445799
TI  - Hrs is a positive regulator of VEGF and insulin signaling.
AB  - Both VEGF and insulin are implicated in the pathogenesis of diabetic retinopathy.
      While it has been established for many years that the number of cell surface
      receptors impacts upon VEGF and insulin action, little is known about the precise
      machinery and proteins driving VEGF-R2 and IR degradation. Here, we investigate
      the role of Hepatocyte growth factor-Regulated tyrosine kinase Substrate (Hrs), a
      regulator of RTK trafficking, in VEGF and insulin signaling. We report that
      ectopic expression of Hrs increases VEGF-R2 and IR number and tyrosine
      phosphorylation, leading to amplification of their downstream signaling. The UIM
      (Ubiquitin Interacting Motif) domain of Hrs is required for Hrs-induced increases
      in VEGF-R2, but not in IR. Furthermore, Hrs is tyrosine-phosphorylated in
      response to VEGF and insulin. We show that the UIM domain is required for Hrs
      phosphorylation in response to VEGF, but not to insulin. Importantly, Hrs co
      localizes with both VEGF-R2 and IR and co-immunoprecipitates with both in a
      manner independent of the Hrs-UIM domain. Finally, we demonstrate that Hrs
      inhibits Nedd4-mediated VEGF-R2 degradation and acts additively with Grb10. We
      conclude that Hrs is a positive regulator of VEGF-R2 and IR signaling and that
      ectopic expression of Hrs protects both VEGF-R2 and IR from degradation.

PMID- 17445800
TI  - Economical LED based, real-time, in vivo imaging of murine corneal wound healing.
AB  - An optimal system for monitoring in vivo corneal wound healing is inexpensive,
      has utility for wounding and imaging, and is able to provide previews before
      photography. We outline such an imaging system that takes advantage of a consumer
      digital camera and an LED-based light source for fluorescein excitation. Using
      FVB/NJ mice, 2mm diameter, circular, axial corneal epithelial defects were
      created using a crescent blade. The corneal wounds were imaged every four hours
      until healed using a Nikon Coolpix 5400 camera attached to a Nikon SMZ-10A
      stereomicroscope, using the illumination from a 16 LED 464nm flashlight. The
      wound area was calculated, and the linear regressions of the linear phase of
      wound healing were compared using the F-test. The slopes of the linear
      regressions for the 6 trials of 4 mice/trial had an average of -52.95microm/h
      (SEM=0.55microm/h) and were statistically equivalent (p>0.05). The mean of the
      R(2) values for the linear regressions was 0.9546 (SEM=0.0121). The equivalent
      linear regressions and R(2)>0.90 suggest that the imaging system could precisely
      monitor the wound healing of multiple trials and of animals within each trial,
      respectively. Using a consumer digital camera and LED-based illumination, we have
      established a system that is economical, is used in both wounding and imaging, is
      operated by a single person, and is able to provide real-time previews to monitor
      corneal wound healing precisely.

PMID- 17445801
TI  - Amyloid, memory and neurogenesis.
AB  - Transgenic mouse models of amyloid deposition consistently demonstrate impaired
      performance on certain tasks of learning and memory. The article by Zhang et al.
      (2006) demonstrates reductions in dentate gyrus neurogenesis in a murine model of
      amyloid deposition which is linked to the deposition of amyloid and not
      overexpression of transgenes. Neurogenesis plays at least a facilitatory role in
      the formation of memory, the nature of which is only beginning to emerge. Thus,
      it seems reasonable to propose that the memory deficits found in the amyloid
      precursor protein transgenic mouse models of amyloid deposition result, at least
      in part, from reduced rates of hippocampal neurogenesis. The possible
      relationship to memory loss in Alzheimer's dementia is also discussed.

PMID- 17445803
TI  - The peroxisomal protein import machinery.
AB  - Peroxisomes are unique organelles whose physiological functions vary depending on
      the cellular environment or metabolic and developmental state of the organism.
      These changes in enzyme content are accomplished by the dynamically operating
      membrane and matrix protein import machineries of peroxisomes that rely on the
      concerted function of at least 20 peroxins. The import of folded matrix proteins
      is mediated by cycling receptors that shuttle between the cytosol and peroxisomal
      lumen. Receptor release back to the cytosol represents the ATP-dependent step of
      peroxisomal matrix protein import, which consists of two energy-consuming
      reactions: receptor ubiquitination and dislocation.

PMID- 17445802
TI  - Ciliary neurotrophic factor is not required for terminal sprouting and
      compensatory reinnervation of neuromuscular synapses: re-evaluation of CNTF null
      mice.
AB  - Loss of synaptic activity or innervation induces sprouting of intact motor nerve
      terminals that adds or restores nerve-muscle connectivity. Ciliary neurotrophic
      factor (CNTF) and terminal Schwann cells (tSCs) have been implicated as molecular
      and cellular mediators of the compensatory process. We wondered if the previously
      reported lack of terminal sprouting in CNTF null mice was due to abnormal
      reactivity of tSCs. To this end, we examined nerve terminal and tSC responses in
      CNTF null mice using experimental systems that elicited extensive sprouting in
      wildtype mice. Contrary to the previous report, we found that motor nerve
      terminals in the null mice sprout extensively in response to major sprouting
      stimuli such as exogenously applied CNTF per se, botulinum toxin-elicited
      paralysis, and partial denervation by L4 spinal root transection. In addition,
      the number, length and growth patterns of terminal sprouts, and the extent of
      reinnervation by terminal or nodal sprouts, were similar in wildtype and null
      mice. tSCs in the null mice were also reactive to the sprouting-stimuli,
      elaborating cellular processes that accompanied terminal sprouts or guided
      reinnervation of denervated muscle fibers. Lastly, CNTF was absent in quiescent
      tSCs in intact, wildtype muscles and little if any was detected in reactive tSCs
      in denervated muscles. Thus, CNTF is not required for induction of nerve terminal
      sprouting, for reactivation of tSCs, and for compensatory reinnervation after
      nerve injury. We interpret these results to support the notion that compensatory
      sprouting in adult muscles is induced primarily by contact-mediated mechanisms,
      rather than by diffusible factors.

PMID- 17445804
TI  - New tensio-active molecules stabilize a human G protein-coupled receptor in
      solution.
AB  - Structural characterization of membrane proteins is hampered by the instability
      of the isolated proteins in detergent solutions. Here, we describe a new class of
      phospholipid-like surfactants that stabilize the G protein-coupled receptor,
      BLT1. These compounds, called C(13)U(9), C(13)U(19), C(15)U(25) and C(17)U(16),
      were synthesized by radical polymerization of Tris(hydroxymethyl)
      acrylamidomethane in the presence of thioglycerol, first endowed with two
      hydrocarbon chains with variable lengths (13-17 carbon atoms), as transfer
      reagent. C(13)U(19), C(17)U(16) or C(15)U(25) significantly enhanced the
      stability of BLT1 in solution compared to what was obtained with common
      detergents. These molecules therefore represent a promising step towards the
      structural characterization of BLT1 and possibly other membrane proteins.

PMID- 17445805
TI  - Assisted reproductive technology practice patterns and the impact of embryo
      transfer guidelines in the United States.
AB  - OBJECTIVE: [1] To evaluate trends in number of embryos transferred and resultant
      high-order multiple (HOM) pregnancy rates by Society for Assisted Reproductive
      Technology (SART)-member clinics between 1996 and 2003 and [2] to relate these
      practice patterns and outcomes to clinic compliance with SART-American Society
      for Reproductive Medicine (ASRM) embryo transfer guidelines. DESIGN:
      Retrospective. SETTING: Society for Assisted Reproductive Technology-member
      fertility centers in the United States. PATIENT(S): Five hundred thirty-six
      thousand, five hundred twenty-four fresh, nondonor IVF cycles. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Number of embryos transferred; pregnancy rates;
      implantation rates; and proportion of singleton, twin, and HOM pregnancies.
      RESULT(S): The number of embryos transferred declined each year. High-order
      multiple pregnancy rates also declined, whereas the twin rates remained stable.
      The most pronounced declines in number transferred occurred immediately after
      publication of SART-ASRM embryo transfer guidelines. After stratifying clinics
      according to mean and modal number of embryos transferred, clinics transferring
      the fewest embryos in women <35 years of age had the highest mean implantation
      and pregnancy rates. Furthermore, the percentage of clinics transferring two
      embryos to a majority of women <35 years of age increased from 3.3% in 1996 to
      49.9% in 2003. CONCLUSION(S): The implementation of SART-ASRM embryo transfer
      guidelines is associated with significant reductions in the number of embryos
      being transferred, along with reductions of HOM pregnancies. Initiatives to
      further reduce twin pregnancies and encourage singleton gestation outcomes are
      outlined.

PMID- 17445806
TI  - Triggering final oocyte maturation using different doses of human chorionic
      gonadotropin: a randomized pilot study in patients with polycystic ovary syndrome
      treated with gonadotropin-releasing hormone antagonists and recombinant follicle
      stimulating hormone.
AB  - OBJECTIVE: To evaluate the effect of different human chorionic gonadotropin (hCG)
      doses on the ongoing pregnancy rates in patients with polycystic ovary syndrome
      (PCOS). DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary
      university referral center. PATIENT(S): Eighty PCOS patients. INTERVENTION(S):
      Patients were randomized to receive 10,000 IU (n = 28), 5000 IU (n = 26), or 2500
      IU (n = 26) of hCG for triggering final oocyte maturation as soon as >or=3 or
      more follicles of 17 mm or larger were present at ultrasound. Patients were
      stimulated with recombinant follicle stimulating hormone (FSH) and daily
      gonadotropin-releasing hormone (GnRH) antagonist, starting on day 6 of
      stimulation. MAIN OUTCOME MEASURE(S): Ongoing pregnancy, fertilization rates.
      RESULT(S): The median fertilization rates were 52.8%, 65.4%, and 55.6% after
      administration of 10,000 IU, 5000 IU and 2500 IU, respectively. The ongoing
      pregnancy rates per PCOS patient receiving hCG were 26.9% (7 of 26), 30.8% (8 of
      26) and 34.8% (8 of 23), respectively. CONCLUSION(S): A decrease in the dose of
      hCG used to trigger final oocyte maturation does not appear to affect adversely
      the probability of pregnancy in PCOS patients treated by IVF using GnRH
      antagonists and recombinant FSH, and further testing in future larger-scale
      trials is recommended.

PMID- 17445807
TI  - Raloxifene increases proliferation of human endothelial cells in association with
      increased gene expression of cyclins A and B1.
AB  - OBJECTIVE: To examine the proliferative effect of of raloxifene on human
      umbilical-vein endothelial cells (HUVECs), and to investigate whether there is an
      associated increased expression of some key regulators of the cell cycle. DESIGN:
      Cell culture for different incubation times. SETTING: University research
      laboratory. PATIENT(S): Sources of HUVECs. INTERVENTION(S): Measurement of cell
      proliferation, of protein levels of cyclin A, cyclin B1, cyclin D1, cyclin
      dependent protein kinase (CDK) 2, CDK4, and p27(Kip1), and of messenger RNA
      expression of cyclin A, cyclin B1, and p27(Kip1). MAIN OUTCOME MEASURE(S): Cell
      proliferation was measured by the 3-(4.5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide assay, the bromo-2'-deoxyuridine assay, and the
      sodium 3'-[1-(phenylaminocarbonyl)-3,4-tetrazolium]-bis (4-methoxy-6-nitro)
      benzene sulfonic acid hydrate assay. Changes in protein expression were measured
      by immunoblotting, and modifications in gene expression were measured by
      quantitative real-time polymerase chain reaction. RESULT(S): Both 1 nM and 10 nM
      of either E(2) or raloxifene achieved a similar increase in cell proliferation.
      The pure antiestrogen ICI 182780 only blocked the E(2)-induced proliferative
      effect. Western blot experiments detected an increase in the expression of only
      cyclin A and B1, and a decreasing trend for p27(Kip1). Enhancements in gene
      expression were observed in response to E(2) and raloxifene for cyclin A and B1.
      No significant changes were found for p27(Kip1). The ICI 182780 effectively
      abrogated the increased gene expression associated with E(2) for cyclin B1, but
      not for cyclin A. In contrast, ICI 182780 was ineffective in the case of
      raloxifene. CONCLUSION(S): Raloxifene increased the proliferation of HUVECs in
      association with enhanced gene expression of cyclins A and B1.

PMID- 17445808
TI  - Miniature hygrometric hot flash recorder.
AB  - OBJECTIVE: To design and test a miniature ambulatory hot flash recorder that uses
      neither electrodes nor gel. DESIGN: In the first study, putative hot flashes
      recorded by using a relative humidity sensor were compared with patient event
      marks. In the second study, relative humidity recorded by using a complete
      prototype recorder was compared with sternal skin conductance recordings made on
      a Biolog recorder, as well as with event marks. SETTING: University medical
      center. PATIENT(S): Ten healthy postmenopausal women reporting frequent hot
      flashes and using no medication. INTERVENTION(S): Body heating in laboratory.
      MAIN OUTCOME MEASURE(S): Positive predictive value (PPV), sensitivity,
      specificity. RESULT(S): In both laboratory studies, the PPV, sensitivity, and
      specificity among all three measures (relative humidity, skin conductance level,
      event) were 100%. In the field, a relative humidity increase of 3% per minute
      compared with skin conductance level-detected hot flashes yielded a PPV of 95.6%,
      a specificity of 95.2%, and a sensitivity of 90.9%. CONCLUSION(S): This device
      should be useful as an endpoint in clinical trials of treatments for hot flashes.

PMID- 17445809
TI  - Use and outcomes of intracytoplasmic sperm injection for non-male factor
      infertility.
AB  - OBJECTIVE: To determine whether intracytoplasmic sperm injection (ICSI) is
      associated with improved outcomes for non-male factor infertility. DESIGN: We
      examined the patient characteristics associated with treatment choice-ICSI and
      conventional in vitro fertilization (IVF)-among patients without a diagnosis of
      male factor infertility and compared outcomes between the two groups, adjusting
      for patient characteristics using multivariate regression models. SETTING:
      Academic fertility center. PATIENT(S): We evaluated 696 consecutive assisted
      reproductive technology (ART) cycles performed for couples with normal semen
      analysis at the Stanford Reproductive Endocrinology and Infertility Center
      between 2002 and 2003. We compared patient characteristics, cycle details, and
      outcomes for ICSI and IVF. MAIN OUTCOME MEASURE(S): Fertilization, pregnancy, and
      live birth rates. RESULT(S): Patient characteristics were similar between the two
      groups, except the proportion of patients with unexplained infertility (IVF 15.1%
      vs. ICSI 23.5%), previous fertility (IVF 62.6% vs. ICSI 45.5%), and previous ART
      cycle (IVF 41.2% vs. ICSI 67.7%). More oocytes were fertilized per cycle for the
      IVF group (6.6 oocytes versus 5.1 oocytes). Fertilization failure, pregnancy, and
      live birth rates did not differ between IVF and ICSI. Using logistic regressions,
      having had previous ART was found to be positively associated with ICSI.
      Treatment choice of ICSI was not associated with fertilization, pregnancy, or
      live birth rates. CONCLUSION(S): No clear evidence of improved outcomes with ICSI
      was demonstrated for non-male factor infertility.

PMID- 17445810
TI  - Doxazosin blockade of alpha 1-adrenergic receptors increases rat serum
      progesterone levels: a putative role of ovarian angiotensin III in
      steroidogenesis.
AB  - OBJECTIVE: To analyze the role of the local renin-angiotensin system (RAS) in the
      female reproductive system to modulate ovarian steroidogenesis and its
      relationship with alpha(1)adrenergic receptors. DESIGN: Observational study.
      SETTING: University laboratory. ANIMAL(S): Adult female Wistar rats treated with
      doxazosin (10 mg/kg) or vehicle for 15 days. INTERVENTION(S): Samples from the
      whole right ovary were dissected after perfusion with saline. The soluble and
      membrane-bound fractions were obtained from these samples. Also, blood samples
      were used to obtain the serum. MAIN OUTCOME MEASURE(S): Fluorometric measurement
      of soluble and membrane-bound RAS-regulating proteolytic regulatory enzyme
      activities by using arylamide derivatives as substrates. Time-resolved
      fluoroimmunoassay of serum E(2) and P. RESULT(S): alpha(1)Adrenergic receptor
      blockade increases ovarian soluble and membrane-bound aminopeptidase A and
      decreases membrane-bound aminopeptidase N and aminopeptidase B. Furthermore,
      serum P levels increased, whereas serum E(2) did not change. CONCLUSION(S):
      Ovarian P production, at least in the rat, is regulated by noradrenaline through
      a mechanism of action in which the RAS is involved, with a main role for
      angiotensin III.

PMID- 17445811
TI  - The prevalence and influence of luteinizing hormone surges in stimulated cycles
      combined with intrauterine insemination during a prospective cohort study.
AB  - OBJECTIVE: To reveal the prevalence of premature LH surges in an IUI program.
      Furthermore, to investigate whether these LH surges influence treatment outcome
      and whether the prevalence of LH surges differs between cycles stimulated with
      clomiphene citrate (CC) and cycles stimulated with recombinant follicle
      stimulating hormone (rFSH). DESIGN: Prospective cohort study. SETTING:
      Subfertility patients in a tertiary institutional hospital. PATIENT(S): A total
      of 66 subfertile couples undergoing ovarian hyperstimulation combined with IUI.
      INTERVENTION(S): The women were randomized through a central blocked computer
      system, either to receive CC (33 couples) or rFSH (33 couples), both combined
      with IUI. Blood for LH determination was drawn on the day of human chorionic
      gonadotropin administration. MAIN OUTCOME MEASURE(S): LH surges as well as
      pregnancy rates. RESULT(S): In a total of 153 cycles, LH was measured. In 36% of
      these cycles, LH surges were detected. The results showed that in 42% of the rFSH
      stimulated cycles an LH surge was detected, compared with 30% in the cycles with
      CC (odds ratio 1.7, 95% confidence interval 0.9 to 3.3). There was a
      nonsignificant trend showing higher pregnancy rates in cycles without an LH surge
      (odds ratio 2.7, 95% confidence interval 0.6 to 13). CONCLUSION(S): Premature LH
      surges occur frequently, and they might influence treatment outcome negatively.
      Strategies to improve treatment outcome might focus on preventing premature LH
      surges.

PMID- 17445812
TI  - Role of treatment with ovarian stimulation and intrauterine insemination in women
      with unilateral tubal occlusion diagnosed by hysterosalpingography.
AB  - OBJECTIVE: To assess the value of controlled ovarian hyperstimulation (COH) and
      IUI in women with unilateral tubal occlusion diagnosed by hysterosalpingography.
      Hysterosalpingography (HSG) is the most common screening test for tubal
      pathology. The management of patients with unilateral tubal occlusion is vague,
      and studies of treatment results with COH and IUI are scarce. DESIGN:
      Retrospective, case-controlled study. SETTING: Referral infertility clinics of a
      national health service. PATIENT(S): The study group consisted of 62 consecutive
      patients treated at our centers for isolated unilateral tubal occlusion by HSG
      between 1998-2005. In all cases, menstrual cycles were regular, and day-3 FSH
      levels and sperm counts were normal. The control group consisted of 115 patients
      with unexplained infertility treated during the same time period. INTERVENTION:
      All patients were treated primarily with three consecutive cycles of COH and IUI,
      with the use of standard protocols of ovarian stimulation with gonadotropins.
      Data analysis included basic clinical parameters, response to ovarian
      stimulation, inseminated sperm parameters, and pregnancy rates (PRs). MAIN
      OUTCOME MEASURE: Cumulative PR for three cycles of COH and IUI. RESULT(S): There
      were no between-group differences in basic clinical and sperm parameters. The
      cumulative PRs after three cycles of COH and IUI were 30.9% for the study group,
      and 42.6% for the control group. The cumulative PR in women with mid-distal or
      distal tubal occlusion was lower, but not of greater statistical significance,
      than in women with proximal tubal occlusion (19% versus 38.2%), and was
      significantly lower than in women with unexplained infertility (19% versus
      42.6%). CONCLUSION(S): Controlled ovarian hyperstimulation with IUI should be
      suggested as the initial treatment of choice in patients with unilateral proximal
      tubal occlusion. The results are similar to those in patients with unexplained
      infertility. However, the outcome of COH with IUI is worse in patients with mid
      distal or distal tubal occlusion on HSG, who should be referred for laparoscopic
      assessment or IVF.

PMID- 17445813
TI  - Ten-year experience with preimplantation genetic diagnosis (PGD) at the New York
      University School of Medicine Fertility Center.
AB  - We describe our experience of over 300 cycles of preimplantation genetic
      diagnosis (PGD) and report clinical pregnancy rates (35%-67%) that support using
      this technology to screen for genetic disorders and chromosomal abnormalities. In
      clinical practice for over ten years, PGD offers couples the earliest form of
      genetic screening and may help improve ongoing pregnancy rates in poor-prognosis
      patients.

PMID- 17445814
TI  - The fluctuating asymmetry of medieval and modern human skulls.
AB  - The analysis of fluctuating asymmetry (FA) allows for estimating the influence of
      stress factors on human development and allows to evaluate resistance to stress.
      FA is often used as a marker of prenatal stress. The aim of this work is to
      estimate the symmetry of skulls from selected historic human populations and to
      analyse changes in their morphology which have taken place over centuries. The
      studied material consisted of two skull samples - a modern sample containing 82
      skulls and a medieval sample of 77 skulls from Grodek on the Bug River.
      Radiographs were taken in postero-anterior (P-A) and base projections. Images
      were scanned and calibrated by means of MicroStation 95 Academic Edition
      software. Measurements of the skull images were used to estimate FA. All data
      were analysed statistically. The skulls in both samples showed asymmetry. The
      levels of FA varied in different skull regions. A high level of FA in the
      calvaria and a low asymmetry for the facial part of skull is characteristic of
      modern skulls. In medieval skulls these relations are inverted. The higher value
      of FA in modern skulls is an evidence of a higher level of developmental stress
      in the modern population as well as of its lesser abilities to resist stress.

PMID- 17445815
TI  - Displaced intra-articular calcaneal fractures: 15-year follow-up of a randomised
      controlled trial of conservative versus operative treatment.
AB  - AIM: To report the 15-year follow-up of displaced intra-articular calcaneal
      fractures from a randomised controlled trial of conservative versus operative
      treatment published in 1993. PATIENTS AND METHODS: Of the initial study, 46
      patients (82%) were still alive at a mean of 15 years post injury and 26 patients
      (57%) agreed to review. The patients had been randomly allocated to either
      conservative or operative treatment in the original study. Clinical [American
      orthopaedic foot and ankle society hindfoot scale (AOFAS), foot function index
      (FFI) and calcaneal fracture score] and radiological (Bohler's angle and
      calcaneum height) outcome measures were used. The grade of osteoarthritis was
      also assessed at long-term follow-up. RESULTS: At long-term follow-up, the
      clinical outcomes were not different between conservative versus operative
      treatment. AOFAS hindfoot scale: conservative=78.5 and operative=70, p=0.11; FFI:
      conservative=24.4 and operative=26.9, p=0.66; calcaneal fracture score:
      conservative=70.1 and operative=63.5, p=0.41. The radiological outcomes were also
      not different between both groups. Bohler's angle: conservative=10.4 degrees and
      operative 16.9 degrees , p=0.07; height of calcaneum: conservative=37.2mm and
      operative=38.2mm, p=0.57; grade of osteoarthritis of the sub-talar joint: p=0.54.
      There was no correlation between Bohler's angle and the outcome measures in
      either group. CONCLUSION: The results of this 15-year follow-up of displaced
      intra-articular calcaneal fracture randomised controlled trial were equivalent
      between conservative and operative treatment and demonstrate similar findings to
      those at one year follow-up.

PMID- 17445816
TI  - Septic shock as a result of group A beta-hemolytic streptococcal meningitis with
      empyema in pregnancy.

PMID- 17445817
TI  - Induction of labor on request in a resource-poor setting.
AB  - OBJECTIVE: To determine the prevalence of and reasons for induction of labor on
      maternal request in a setting where aversion to induction of labor is the norm.
      METHOD: Women undergoing induction of labor on maternal request at three
      maternity centers in Enugu, Nigeria were interviewed by means of pre-tested self
      administered questionnaires. The outcomes of labor in these women were also
      compared with those of a control group consisting of women who had induction of
      labor for medical reasons. RESULTS: The prevalence of induction of labor on
      maternal request was 7.4%. Maternal convenience was the commonest reason for
      request induction. The outcomes of labor were similar between the subjects and
      their controls. CONCLUSION: Nigerian women are beginning to request induction of
      labor without medical indications and have comparable outcomes with those who
      have medical indications. There is need for appropriate regulatory guidelines.

PMID- 17445818
TI  - Bilateral ovarian metastasis on transposed ovaries from cervical carcinoma.

PMID- 17445819
TI  - The impact of female genital cutting on health of newly married women.
AB  - OBJECTIVE: To detect the rate of female genital cutting among a sample of newly
      married women in Benha city, and make a comparison between circumcised and non
      circumcised women regarding long-term health problems. METHODS: Randomly selected
      (264) newly married women were the subjects of this work. RESULTS: Circumcised
      group constitutes 75.8% of the sample. All non-circumcised women were living in
      an urban area. Dysmenorrhea was more common among circumcised rather than non
      circumcised, with statistically significant difference (P<0.01). Marital problems
      (dyspareunia, loss of libido, failure of orgasm and husband's dissatisfaction)
      had statistically different levels of significance among circumcised women.
      Obstetric problems such as tears, episiotomy and consequently distressed babies
      were more events among circumcised mothers with statistical significance.
      Circumcised females had significant mental problems such as somatization, anxiety
      and phobia (P<0.001). CONCLUSION: Female genital cutting remains a widely
      practiced custom in our society. Grave complications of circumcision may last
      throughout women's life particularly the time of consummation of marriage and the
      time of childbirth.

PMID- 17445820
TI  - Application and validation of the lattice Boltzmann method for modelling flow
      related clotting.
AB  - The purpose of this paper is to present a simple clotting model, based on
      residence time and shear stress distribution, that can simulate the deposition
      over time of enzyme-activated milk in an in vitro system. Results for the model
      are compared with experiments exhibiting clot deposition in the region of a sharp
      edged stenosis. The milk experiments have been shown to be a valuable analogue
      for the experimental representation of flow-induced blood clotting, particularly
      in the context of separation of hydrodynamic from biochemical factors. The
      facility to predict the flow-induced clotting of the blood analogue, in which the
      chemistry reduces to what is effectively a zeroth order reaction, gives
      confidence in this physics-based approach to simulation of the final part of the
      coagulation cascade. This type of study is a necessary precursor to the
      development of a complex, multi-factorial, biochemical model of the process of
      thrombosis. In addition to the clotting simulations, comparisons are reported
      between the computed flow patterns prior to clot deposition and flow
      visualisation studies. Excellent agreement of hydrodynamic parameters is reported
      for a Reynolds number of 100, and qualitative agreement is seen for the complex,
      disturbed flow occurring at a physiologically relevant Reynolds number of 550.
      The explicit, time-stepping lattice Boltzmann approach may have particular merit
      for the transitional flow at this higher Reynolds number.

PMID- 17445821
TI  - A new model to predict in vivo human knee kinematics under physiological-like
      muscle activation.
AB  - Although a number of approaches have attempted to model knee kinematics, rarely
      have they been validated against in vivo data in a larger subject cohort. Here,
      we assess the feasibility of four-bar linkage mechanisms in addressing knee
      kinematics and propose a new approach that is capable of accounting for
      lengthening characteristics of the ligaments, including possible laxity, as well
      as the internal/external rotation of the joint. MR scans of the knee joints of 12
      healthy volunteers were taken at flexion angles of 0 degrees , 30 degrees and 90
      degrees under both passive and active muscle conditions. By reconstructing the
      surfaces at each position, the accuracy of the four-bar linkage mechanism was
      assessed for every possible combination of points within each cruciate ligament
      attachment area. The specific set of parameters that minimized the deviation
      between the predictions and the in vivo pose was derived, producing a mean error
      of 1.8 and 2.5 on the medial and 1.7 and 2.4mm on the lateral side at 30 degrees
      and 90 degrees flexion, respectively, for passive motion, significantly improving
      on the models that did not consider internal/external rotation. For active
      flexion, mean medial errors were 3.3 and 4.7 mm and lateral errors 3.4 and 4.8
      mm. Using this best parameter set, a generic predictive model was created and
      assessed against the known in vivo positions, producing a maximum average error
      of 4.9 mm at 90 degrees flexion. The accuracy achieved shows that kinematics may
      be accurately reconstructed for subject specific musculoskeletal models to allow
      a better understanding of the load distribution within the knee.

PMID- 17445823
TI  - A finite element model of loading and unloading of an asperity contact with
      adhesion and plasticity.
AB  - An elastic-plastic microcontact with adhesion was studied using a finite element
      model. This model differs from the existing models, in that it includes the
      effect of adhesion on the deformation and stresses field, making it applicable to
      a wide range of material properties. It shows two distinct separation modes,
      brittle separation and ductile separation. To the best of our knowledge this is
      the first time that a finite element model has predicted ductile separation in an
      adhesive contact. Three key parameters affecting the contact and separation modes
      are also discussed. Further work is expected to fully reveal the effect of these
      parameters on the separation modes.

PMID- 17445824
TI  - Electrochemical behavior and luminescent properties of a multilayer film
      containing mixed-addenda polyoxometalates K10H3[Eu(SiMo9W2O39)2] and tris(2,2'
      bipyridine)ruthenium(II).
AB  - Inorganic-organic composite films containing the mixed-addenda heteropolytungsto
      molybdate K(10)H(3)[Eu(SiMo(9)W(2)O(39))(2)]xH(2)O (abbreviated as EuSiMo(9)W(2))
      and tris(2,2'-bipyridine)ruthenium(II) Ru(bpy)(2+)(3) (abbreviated as Ru(bpy)(3))
      were fabricated by the layer-by-layer self-assembly method. UV-vis spectroscopy
      shows that the absorbance values at characteristic peaks increase linearly with
      the number of EuSiMo(9)W(2)/Ru(bpy)(3) bilayers, suggesting that the deposition
      process is linear and highly reproducible from layer to layer. The composition of
      the multilayer film was measured by X-ray photoelectron spectra. Atomic force
      microscopy presented a correspondingly uniform surface morphology and a
      homogeneity of the multilayer films. The film exhibited photoluminescence arising
      from the d-pi* metal-to-ligand transition of Ru(2+), and (5)D(0) metastable state
      to terminate levels in the (7)F(J) (J=0-4) ground-state multiplet transitions of
      Eu(3+). The film also exhibited catalytic activities toward the reduction of IO(
      )(3), H(2)O(2), BrO(-)(3), NO(-)(2) and the oxidation of C(2)O(2-)(4). It may
      provide a novel material as bifunctional electrocatalysts and fluorescence probes
      in biochemistry, luminescence sensors, electroluminescent optical devices, and so
      on.

PMID- 17445825
TI  - Cleavage of phosphate diesters mediated by Zn(II) complex in Gemini surfactant
      micelles.
AB  - The cleavage of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) catalyzed by the
      Zn(II)-biap (biap: N,N-bis(2-ethyl-5-methylimidazole-4-ylmethyl)aminopropane)
      complex has been investigated spectrophotometrically in a micellar solution of
      cationic Gemini surfactant 16-2-16 [bis(hexadecyldimethylammonium)ethane bromide]
      and CTAB (hexadecyltrimethylammonium bromide) at 25+/-0.1 degrees C. The
      experimental results reveal that a higher rate of acceleration (about 2016-fold)
      of HPNP cleavage promoted by the Zn(II)-biap complex has been observed in the 16
      2-16 micellar solution in comparison with the background rate (k(0)) of HPNP
      spontaneous cleavage at 25 degrees C. Reaction rates of HPNP cleavage in CTAB
      micellar solutions are only about 40% of that in Gemini 16-2-16 micelles under
      comparable conditions. In addition, the cleavage rates of HPNP in Gemini micelles
      and in CTAB micelles are respectively 29.5 times and 12 times faster than that in
      aqueous buffer. Especially, a "sandwich absorptive mode" has been proposed to
      explain the acceleration of HPNP cleavage in a cationic micellar solution.

PMID- 17445826
TI  - An experimental method for the measurement of the stability of concentrated
      magnetic fluids.
AB  - In this paper we present a device and method suited to the experimental
      determination of the sedimentation rate of concentrated suspensions of magnetic
      particles. The method is based on the measurement of the inductance of one or
      more sensing coils located at specified positions around a test tube containing
      the suspension. Such measurement is made possible by the determination of the
      resonant frequency of a parallel LC circuit in which L is the inductance of the
      sensing coil and C is the capacity of a capacitor chosen in such a way that the
      resonant frequency is easily measured. Upon calibration it is possible to relate
      the resonant frequency to the volume fraction of the particles at the coil
      location. The method is applied in the present work to the evaluation of the
      sedimentation kinetics of iron suspensions in base fluids of viscosities ranging
      from 0.3 to 100 mPa s and volume fractions of solids between 2.5 and 25%. Both if
      a single coil is used and if a set of three coils at different positions are
      employed, it is possible to detect the rate of accumulation of particles at the
      bottom of the container as well as a phenomenon of buoyancy of the largest
      particles brought about by the hydrostatic push of a dense fluid consisting of
      the smallest particles in the supporting liquid.

PMID- 17445827
TI  - Efficacy of transgenic rice expressing Cry1Ac and CpTI against the rice
      leaffolder, Cnaphalocrocis medinalis (Guenee).
AB  - Detached leaf bioassays, open field tests and cage tests were conducted to
      evaluate the control efficacy of two transgenic rice lines, expressing Cry1Ac and
      CpTI, against Cnaphalocrocis medinalis (Guenee) during 2005-2006 in Fuzhou,
      China. Bioassay results showed that cumulative feeding areas of C. medinalis on
      transgenic lines were significantly lower than that on control rice lines at
      different developmental stages. The corrected mortalities at 96 h after
      infestation on transgenic lines during six rice growth stages were >90% and 100%
      during experiments conducted in 2005 and 2006, respectively. In the open field
      test, there was no significant difference in egg density between transgenic and
      control lines during early days of infestation, but significant differences were
      detected in late season, due to serious damage on control lines. Larval densities
      on control lines were significantly higher than the low larval populations
      observed on transgenic lines during both seasons. The percentages of plants with
      folded leaves and percentages of folded leaves on transgenic lines were
      significantly lower than that on control lines with and without insecticide
      applications, during the entire season. In cage tests the cumulative numbers of
      C. medinalis adults derived from transgenic lines were significantly lower than
      that from control lines with and without insecticide treatments. The high level
      of efficacy of the two transgenic rice lines against C. medinalis may provide an
      important basis for reduced insecticide applications, an expansion of alternative
      pest-control strategies and insect resistance management of Bt rice in the
      future.

PMID- 17445828
TI  - Structure of a high-affinity "mimotope" peptide bound to HIV-1-neutralizing
      antibody b12 explains its inability to elicit gp120 cross-reactive antibodies.
AB  - The human antibody b12 recognizes a discontinuous epitope on gp120 and is one of
      the rare monoclonal antibodies that neutralize a broad range of primary human
      immunodeficiency virus type 1 (HIV-1) isolates. We previously reported the
      isolation of B2.1, a dimeric peptide that binds with high specificity to b12 and
      competes with gp120 for b12 antibody binding. Here, we show that the affinity of
      B2.1 was improved 60-fold over its synthetic-peptide counterpart by fusing it to
      the N terminus of a soluble protein. This affinity, which is within an order of
      magnitude of that of gp120, probably more closely reflects the affinity of the
      phage-borne peptide. The crystal structure of a complex between Fab of b12 and
      B2.1 was determined at 1.8 A resolution. The structural data allowed the
      differentiation of residues that form critical contacts with b12 from those
      required for maintenance of the antigenic structure of the peptide, and revealed
      that three contiguous residues mediate B2.1's critical contacts with b12. This
      single region of critical contact between the B2.1 peptide and the b12 paratope
      is unlikely to mimic the discontinuous key binding residues involved in the full
      b12 epitope for gp120, as previously identified by alanine scanning substitutions
      on the gp120 surface. These structural observations are supported by experiments
      that demonstrate that B2.1 is an ineffective immunogenic mimic of the b12 epitope
      on gp120. Indeed, an extensive series of immunizations with B2.1 in various forms
      failed to produce gp120 cross-reactive sera. The functional and structural data
      presented here, however, suggest that the mechanism by which b12 recognizes the
      two antigens is very different. Here, we present the first crystal structure of
      peptide bound to an antibody that was originally raised against a discontinuous
      protein epitope. Our results highlight the challenge of producing immunogens that
      mimic discontinuous protein epitopes, and the necessity of combining
      complementary experimental approaches in analyzing the antigenic and immunogenic
      properties of putative molecular mimics.

PMID- 17445829
TI  - The structure of OMCI, a novel lipocalin inhibitor of the complement system.
AB  - The complement (C) system is a potent innate immune defence system against
      parasites. We have recently characterised and expressed OmCI, a 16 kDa protein
      derived from the soft tick Ornithodoros moubata that specifically binds C5,
      thereby preventing C activation. The structure of recombinant OmCI determined at
      1.9 A resolution confirms a lipocalin fold and reveals that the protein binds a
      fatty acid derivative that we have identified by mass spectrometry as ricinoleic
      acid. We propose that OmCI could sequester one of the fatty acid-derived
      inflammatory modulators from the host plasma, thereby interfering with the host
      inflammatory response to the tick bite. Mapping of sequence differences between
      OmCI and other tick lipocalins with different functions, combined with
      biochemical investigations of OmCI activity, supports the hypothesis that OmCI
      acts by preventing interaction with the C5 convertase, rather than by blocking
      the C5a cleavage site.

PMID- 17445830
TI  - Monomeric restriction endonuclease BcnI in the apo form and in an asymmetric
      complex with target DNA.
AB  - Restriction endonuclease BcnI cleaves duplex DNA containing the sequence CC/SGG
      (S stands for C or G, / designates a cleavage position) to generate staggered
      products with single nucleotide 5'-overhangs. Here, we show that BcnI functions
      as a monomer that interacts with its target DNA in 1:1 molar ratio and report
      crystal structures of BcnI in the absence and in the presence of DNA. In the
      complex with DNA, BcnI makes specific contacts with all five bases of the target
      sequence and not just with a half-site, as the protomer of a typical dimeric
      restriction endonuclease. Our data are inconsistent with BcnI dimerization and
      suggest that the enzyme introduces double-strand breaks by sequentially nicking
      individual DNA strands, although this remains to be confirmed by kinetic
      experiments. BcnI is remotely similar to the DNA repair protein MutH and shares
      approximately 20% sequence identity with the restriction endonuclease MvaI, which
      is specific for the related sequence CC/WGG (W stands for A or T). As expected,
      BcnI is structurally similar to MvaI and recognizes conserved bases in the target
      sequence similarly but not identically. BcnI has a unique machinery for the
      recognition of the central base-pair.

PMID- 17445831
TI  - A randomized, double-blind comparison of duloxetine and venlafaxine in the
      treatment of patients with major depressive disorder.
AB  - BACKGROUND: Clinical trials assessing antidepressant therapies typically include
      separate assessments of efficacy (benefit) and adverse events (risk). Global
      benefit-risk (GBR) assessment allows the simultaneous evaluation of both efficacy
      and adverse events. The objective was to compare the serotonin and norepinephrine
      reuptake inhibitors (SNRIs) duloxetine and venlafaxine using GBR assessment.
      METHODS: Data were combined from two similarly designed, multicenter, randomized,
      double-blind, parallel group studies in which patients with major depressive
      disorder were randomized to either duloxetine 60 mg/day or venlafaxine extended
      release (XR) 150 mg/day (75 mg/day for the first 2 weeks) for a 6-week fixed
      dosing period followed by an additional 6 weeks of treatment in which the dose
      could be increased up to 120 mg/day for duloxetine and 225 mg/day for
      venlafaxine. Patients completing the study (or receiving study drug for 2 weeks
      or more) were eligible to enter a taper period where the dose of study drug was
      gradually reduced over 1-2 weeks prior to drug discontinuation. The primary
      outcome measure (defined a priori) was the GBR comparison of duloxetine 60 mg/day
      and venlafaxine XR 150 mg/day after 6 weeks of treatment. In the GBR analysis,
      benefit was defined as remission at endpoint [17-item Hamilton Depression Rating
      Scale (HAMD17) 7]. Risk was defined by four categories: patients having either no
      adverse events (AEs), AEs with no severity rating greater than moderate, AEs with
      at least one severity rating of severe, or having discontinued with a reason of
      self-reported adverse event (regardless of any AE severity). Additional efficacy
      measures included HAMD17 total score and subscales, HAMA, CGI-S, and PGI-I.
      Safety and tolerability were assessed via analysis of reasons for
      discontinuation, treatment-emergent adverse events (TEAEs), discontinuation
      emergent adverse events, and changes in vital signs, weight, and laboratory
      analytes. RESULTS: There were no significant differences between duloxetine 60
      mg/day and venlafaxine 150 mg/day as measured by GBR assessment at the end of 6
      weeks (-1.418 vs. -1.079, P = 0.217) or 12 weeks (-0.349 vs. -0.121, P = 0.440),
      nor were there significant differences between treatment groups on the majority
      of efficacy measures. Significantly more venlafaxine-treated patients (74.5%)
      completed 12 weeks of treatment compared with duloxetine-treated patients (64.8%,
      P =.006). Nausea was the most common treatment-emergent adverse event (TEAE) for
      both drugs, and was significantly higher with duloxetine 60 mg/day compared to
      venlafaxine 150 mg/day during the first 6 weeks of treatment (43.6% vs. 35.0%,
      P0.05). During the taper period, significantly more venlafaxine-treated patients
      reported discontinuation-emergent adverse events (DEAEs) than duloxetine-treated
      patients. From a safety perspective, significantly more venlafaxine-treated
      patients (n = 4) than duloxetine-treated patients (n=0, P =.047) experienced
      sustained elevations of systolic blood pressure during the fixed dosing period.
      Otherwise, there were few significant differences in safety measures found
      between treatment groups during 6 and 12 weeks of therapy. CONCLUSIONS:
      Duloxetine 60 mg/day and venlafaxine XR 150 mg/day have similar benefit-risk
      profiles on the basis of a comparison utilizing GBR assessment. The implications
      of the more subtle differences between these drugs, as well as for interpreting
      the GBR assessment, are discussed.

PMID- 17445832
TI  - Freezing and hypokinesia of gait induced by stimulation of the subthalamic
      region.
AB  - We report a case of a Parkinson's disease patient treated by bilateral deep brain
      stimulation of the subthalamic nucleus, who developed freezing and hypokinesia of
      gait induced by stimulation through a left-side misplaced electrode which was
      more antero-medial than the planned trajectory. Subsequently, correct
      repositioning of the left electrode afforded complete relief of gait
      disturbances. Freezing and hypokinesia of gait may be side effects of deep brain
      stimulation of the subthalamic region due to current spreading antero-medially to
      the subthalamic nucleus. These side effects are not subject to habituation and
      restrict any increase in stimulation parameters. We hypothesize that pallidal
      projections to the pedunculopontine nucleus could be responsible for these gait
      disturbances in our patient.

PMID- 17445833
TI  - Clinical diagnosis of vascular dementia.
AB  - Vascular dementia (VaD) is a heterogeneous clinical entity based on various
      vascular pathophysiological processes underlying the subtypes of cerebrovascular
      disease (CVD). Several diagnostic criteria are currently being used for the
      clinical diagnosis of VaD, but they are mostly more than 10 years old and need to
      be renovated including the use of functional brain imaging methods such as single
      photon emission computerized tomography (SPECT). There is a limitation in the
      diagnosis based on the strict dichotomy between AD and VaD, and the concept of
      "AD with CVD" or "mixed dementia" should be included in the clinical diagnosis of
      VaD.

PMID- 17445834
TI  - A review of psychosocial aspects of motor neurone disease.
AB  - Motor neurone disease (MND) is an illness involving the progressive degeneration
      of upper and lower motor neurones. There is no known cause or cure. The physical
      aspects of MND frequently receive the majority of attention, with psychosocial
      aspects accorded secondary importance. We undertook a comprehensive search of the
      available literature published between 1966 and 2006 on the psychosocial aspects
      of MND, including quality of life (QoL), depression, social support, life
      sustaining treatment (LST), coping, spirituality and current practice. The
      literature identified that QoL correlated more strongly with measures of
      suffering, social support and hopelessness than with the physical state of the
      patient. Depression is relatively common (prevalence rates up to 50%), as are
      other forms of psychological distress in the MND population, and is not
      associated with illness severity and functional status. Depression strongly
      correlates with QoL. Social support is often limited for MND patients and this
      also influences QoL. Hope and hopelessness are important issues for MND patients
      with hopelessness contributing significantly to suffering and, for some, a desire
      for hastened death. Choices and decisions about life sustaining treatments pose a
      burden for patients and carers. Despite the physical and emotional suffering
      associated with MND, a significant number cope well and find positive meaning in
      life. Many patients opting for life sustaining treatment report a satisfactory
      QoL. In conclusion, psychosocial aspects of life are important for patients with
      MND. Depression and other expressions of distress require recognition and
      treatment. Issues of hope, spirituality and life and death also require attention
      in clinical practice. Although guidelines exist to direct physicians to attend to
      the physical care, there is a distinct lack of guidance to attend to the
      psychological state of the MND patient.

PMID- 17445835
TI  - Occurrence of hydroxylated polychlorinated biphenyls in the brain of cetaceans
      stranded along the Japanese coast.
AB  - Levels of hydroxylated polychlorinated biphenyls (OH-PCBs) and PCBs were measured
      in the brain of melon-headed whales (MW: Peponocephala electra), striped dolphins
      (SD: Stenella coeruleoalba) and finless porpoises (FP: Neophocaena phocaenoides)
      stranded along the Japanese coast during 2002-2003. Levels of OH-PCBs (including
      identified and unknown OH-P(5)CB, -H(6)CB, -H(7)CB and O(8)CB congeners) in the
      brain of MW, SD and FP were in the range of 20-290, 21-330 and 170-240pg/g wet
      wt., respectively. Observed OH-PCB levels were 2-3 orders of magnitude lower than
      PCBs in the same individuals. OH-PCBs/PCBs ratios in MW, SD and FP brain were
      lower than those in blood of humans and wildlife and in the brain of polar bears
      reported previously. OH-PCBs were also detected in maternal and fetal brain of SD
      (1 pair), suggesting transfer of OH-PCBs into the fetal brain of odontocete
      cetaceans. When fetus/dam concentration ratios of OH-PCB congeners detected in
      maternal and fetal brain were estimated, the values were higher than those of PCB
      congeners, implying that OH-PCBs in maternal blood could be more easily
      transferred into fetal brain via placenta than PCBs.

PMID- 17445836
TI  - The analysis and regulation for the dynamics of a temperate bacteriophage model.
AB  - The purpose of this paper is to study the asymptotical behavior of a temperate
      bacteriophage model in chemostat, which was first proposed by Levin et al. [B.R.
      Levin, F.M. Stewart, L. Chao, Resource-limited growth, competition and predation:
      A model and experiment studies with bacteria and bacteriophage, Am. Nat. 125
      (1977) 3]. Firstly, a classification for the equilibria of the model and their
      stability are obtained; secondly, sufficient conditions for uniform persistence
      are obtained; thirdly, sufficient conditions for the global asymptotic behavior
      are given, and simulations for the model are presented. The theoretical results
      show that there are more than eight cases for the classification of the model,
      and that the decrease (increase) of the nutrient concentration or average lytic
      time (flow rate) is beneficial to the survival of the sensitive cells. Both the
      simulated and theoretical results show that there is a possibility of switch
      phenomena or a periodical outburst of the phages and the lysogens, which is
      caused by the internal factors rather than by some external environment. Finally,
      the simulation and regulation of the dynamics of the model with experimental data
      are presented.

PMID- 17445837
TI  - Noncovalent interactions with DNA: an overview.
AB  - Over the last four decades, intense research has focused on the effects of small
      organic compounds that noncovalently bind to nucleic acids. These interactions
      have been shown to disrupt replication and/or transcription culminating in
      cellular death. Accordingly, DNA binding compounds have potential applications as
      anti-cancer and anti-viral agents. This report provides an overview of the
      different DNA-binding modes with an emphasis on DNA groove specificity for the
      groove-binding and intercalation modes. While most DNA-interacting agents
      selectively bind to DNA by either groove binding or intercalation, some compounds
      can exhibit both binding modes. The binding mode with the most favorable free
      energy for complex formation depends on the DNA sequence and structural features
      of the bound ligand.

PMID- 17445838
TI  - The relationship between biomarkers of oxidative DNA damage, polycyclic aromatic
      hydrocarbon DNA adducts, antioxidant status and genetic susceptibility following
      exposure to environmental air pollution in humans.
AB  - Polycyclic aromatic hydrocarbons (PAHs) appear to be significant contributors to
      the genotoxicity and carcinogenicity of air pollution present in the urban
      environment for humans. Populations exposed to environmental air pollution show
      increased levels of PAH DNA adducts and it has been postulated that another
      contributing cause of carcinogenicity by environmental air pollution may be the
      production of reactive oxygen species following oxidative stress leading to
      oxidative DNA damage. The antioxidant status as well as the genetic profile of an
      individual should in theory govern the amount of protection afforded against the
      deleterious effects associated with exposure to environmental air pollution. In
      this study we investigated the formation of total PAH (bulky) and B[a]P DNA
      adducts following exposure of individuals to environmental air pollution in three
      metropolitan cities and the effect on endogenously derived oxidative DNA damage.
      Furthermore, the influence of antioxidant status (vitamin levels) and genetic
      susceptibility of individuals with regard to DNA damage was also investigated.
      There was no significant correlation for individuals between the levels of
      vitamin A, vitamin E, vitamin C and folate with M(1)dG and 8-oxodG adducts as
      well as M(1)dG adducts with total PAH (bulky) or B[a]P DNA adducts. The
      interesting finding from this study was the significant negative correlation
      between the level of 8-oxodG adducts and the level of total PAH (bulky) and B[a]P
      DNA adducts implying that the repair of oxidative DNA damage may be enhanced.
      This correlation was most significant for those individuals that were non smokers
      or those unexposed to environmental air pollution. Furthermore the significant
      inverse correlation between 8-oxodG and B[a]P DNA adducts was confined to
      individuals carrying the wild type genotype for both the GSTM1 and the GSTT1 gene
      (separately and interacting). This effect was not observed for individuals
      carrying the null variant.

PMID- 17445839
TI  - Loss of nuclear BRCA1 protein staining in normal tissue cells derived from BRCA1
      and BRCA2 mutation carriers.
AB  - Enhanced genomic instability has been recently reported in normal cells derived
      from BRCA1/2 mutation carriers when placed in vitro in non-physiological stress
      conditions. We present here original data which help to explain the observed
      genomic instability. Leucocytes from BRCA1/2 mutation carriers, sporadic breast
      cancer patients and controls were prepared for BRCA1 immunocytochemistry. We show
      that BRCA1 containing nuclear dot like structures are detectable in about 80% of
      the leucocytes from controls and sporadic breast cancer patients, but are absent
      in the majority of normal cells from BRCA1 as well as BRCA2 mutation carriers
      (also in their normal breast cells). Our results thus indicate that the genomic
      instability observed in normal cells from BRCA1 and BRCA2 mutation carriers is
      associated with a down-regulation of nuclear BRCA1 protein accumulation in the
      dot like structures. These results suggest in addition that immunocytochemical or
      alternative molecular screening strategies might help to identify women with a
      high risk for breast (ovarian) cancer even when the underlying genetic defect
      remains undetectable.

PMID- 17445840
TI  - [Intracranial ependymomas in adult patients. Diagnosis and histological
      prognostic factors].
AB  - BACKGROUND: Intracranial ependymomas are rare in adults and histopathological
      prognostic factors are poorly determined. PURPOSE: A retrospective multicentric
      study was conducted in France in order to assess the prognostic value of
      histology. MATERIAL: Between 1990 and 2004, 216 adult patients with newly
      diagnosed ependymomas were treated in 19 French centers. Eligibility required
      institutional histopathological confirmation of an ependymoma and available
      clinical history and MRI features (see comparison paper). METHODS: Histological
      preparations and one paraffin embedded block from each patient were sent to Pr D.
      Figarella-Branger in Marseille. Central review by four neuropathologists (D.
      Figarella-Branger, A. Maues de Paula, C. Fernandez and A. Jouvet) was performed.
      Specimens for which all pathologists agreed with the histological diagnosis of
      ependymomas were included, whereas cases for which all disagree were excluded and
      reclassified. In the event of doubt and/or discrepancies between pathologists
      immunostaining was performed in order to reach a consensus diagnosis. Diagnostic
      of ependymomas was confirmed in 121 cases (56%). In theses cases, ependymomas
      were classified according to the WHO system (subtype and grade). The potential
      prognostic value (overall survival OS and disease free survival DFS) of the
      following histological parameters was examined: perivascular pseudorosettes,
      ependymal rosettes, hyalinized vessels, mitotic index, microvascular
      proliferation, necrosis, area of increased cellularity, nuclear atypia, brain
      invasion and Mib-1 labelling index. RESULTS: Among the 121 ependymomas, 88 were
      grade II (47 classic, 17 cellular, 2 papillar, 6 clear cells and 16 tanicytic)
      and 33 grade III. WHO grading, occurrence of microvascular proliferation,
      necrosis, nuclear atypia and high proliferative index were correlated with both
      OS and DFS. Moreover, quantification of certain parameters enabled a reproducible
      grading system correlated with both OS and DFS.

PMID- 17445841
TI  - [Spontaneous supratentorial cerebral hemorrhage: role of surgical treatment].
AB  - Until very recently, no specific therapies have been demonstrated to improve
      outcome after spontaneous intracerebral haemorrhage (ICH). The STICH (surgical
      treatment for intracerebral haemorrhage) study showed no overall benefit from
      early surgery when compared with initial conservative treatment. In contrast, the
      stereotactic aspiration technique can be safely performed and in a uniform
      manner. Despite the reduction of ICH volume, no improvement in mortality and
      functional result was obtained. Endoscopy is a new therapeutic option for ICH
      with good results for hematoma removal. Based on these feasibility studies, a
      randomized control trial regarding this procedure would be required to assess the
      efficacy of this procedure. Due to the lack of benefit observed in the recent
      STICH trial, emergency surgical evacuation should be reserved for patients with
      large lobar haemorrhage, mass effect and rapidly deteriorating clinical
      condition.

PMID- 17445842
TI  - Carbamazepine prevents breakdown of neurotransmitter release induced by
      hyperactivation of ryanodine receptor.
AB  - To clarify the mechanisms of the pharmacological action of carbamazepine (CBZ),
      we determined the effect of CBZ on GABA and glutamate release associated with the
      ryanodine receptor (Ryr)-sensitive Ca(2+)-induced Ca(2+)-releasing system (CICR)
      in the rat hippocampus using microdialysis. The therapeutically relevant
      concentration of CBZ increased basal GABA release without affecting basal
      glutamate release; however, K(+)-evoked releases were concentration-dependently
      reduced by CBZ. Lower-concentration ryanodine increased basal and K(+)-evoked
      releases of GABA and glutamate in a concentration dependent manner, whereas
      higher-concentration ryanodine reduced them. These inflection points in the
      concentration-response curves of ryanodine for neurotransmitter release (critical
      concentrations) were shifted to the left by K(+)-evoked stimulation. The critical
      concentration of ryanodine in GABA release was lower than that in glutamate
      release. During the resting stage, the critical concentrations of ryanodine were
      unaffected by inhibition of L-type, N-type and P-type voltage-sensitive Ca(2+)
      channels (VSCCs) but were prevented by CBZ; however, during the neuronal
      hyperexcitable stage, the critical concentration was increased by CBZ, L-type and
      P-type VSCC inhibitors but not the N-type VSCC inhibitor. Therefore, a
      therapeutically relevant concentration of CBZ protects against the breakdown of
      the neurotransmitter release mechanism induced by hyperactivation of Ryr via
      inhibition of L-type and P-type VSCCs as well as inhibition of Ryr-sensitive
      CICR. These actions of CBZ appear to be involved, at least partially, in its anti
      seizure mechanisms.

PMID- 17445843
TI  - Analgesic tolerance to microinjection of the micro-opioid agonist DAMGO into the
      ventrolateral periaqueductal gray.
AB  - Repeated administration of the relatively low-efficacy micro-opioid receptor
      agonist morphine induces tolerance to its antinociceptive effects. High-efficacy
      agonists such as D-Ala2NMePhe4,Gly-ol5 (DAMGO) have been shown to be less
      effective at producing tolerance, suggesting that different neural mechanisms
      underlie tolerance to these agonists. However, the correlation between agonist
      efficacy and tolerance development has not been examined within the ventrolateral
      periaqueductal gray (vPAG), a brain area known to be crucial for the development
      of morphine tolerance. The current studies examined whether tolerance to DAMGO
      occurs within the vPAG, and whether repeated treatment with DAMGO into the vPAG
      alters the development of morphine tolerance. The results showed that repeated
      vPAG microinjections of DAMGO induced robust tolerance and cross-tolerance to
      morphine. Further, co-administration of a low dose of DAMGO with morphine
      potentiated morphine tolerance. These findings indicate that similar mechanisms
      underlie tolerance to morphine and DAMGO within the vPAG.

PMID- 17445844
TI  - Neural correlates of recollection and familiarity: a review of neuroimaging and
      patient data.
AB  - Dual-process models of recognition memory suggest that two processes contribute
      to performance: recollection and familiarity. Recent work suggests that the two
      processes are dissociable at the level of the brain. Here we review 12 studies
      that used event-related functional magnetic resonance imaging (fMRI), and 21
      studies of patients with damage to various brain regions, which examined
      recollection and familiarity using the 'Remember-Know' (R/K), process
      dissociation procedure (PDP), or receiver operator characteristic (ROC) memory
      paradigms, for insights into the neural basis of each process. Results show that
      recollection and familiarity are characterized by different patterns of brain
      activity in frontal, parietal, sensory, and medial temporal cortices. Results
      suggest that recollection and familiarity cannot be dissociated based on
      confidence levels alone, and that the two processes are not exclusive. Based on
      these results, we propose a model in which recollection and familiarity can be
      dissociated in two ways: recruitment of additional brain regions in frontal,
      medial temporal, and content-specific cortices during recollection, and in
      variations in coherence of brain networks activated during recollective- or
      familiarity-based processing.

PMID- 17445845
TI  - Thyroxine replacement in an animal model of congenital hypothyroidism.
AB  - This study examined the effects of thyroxine (T(4)) treatment on spatial learning
      and memory in congenitally hypothyroid (CH) rats. Forty CH male offspring of
      methimazole-treated dams were randomly divided into three groups: no T(4)
      (vehicle) treatment (n=12), T(4) treatment commencing on postnatal day (P-) 7
      (n=14), and T(4) treatment commencing on P-21 (n=14). Normal male rats were used
      as a control group (n=14). T(4) was administered daily (sc, 0.02 microg/g) to the
      treatment groups for 30 days. A water-maze was used to assess behaviour at 42, 70
      and 98 days of age. T(4) treatment beginning at P-7 improved learning and memory
      associated with CH at 70 and 98 days of age but T(4) treatment beginning at P-21
      did not improve CH-impaired learning and memory.

PMID- 17445846
TI  - An antifungal compound involved in symbiotic germination of Cypripedium
      macranthos var. rebunense (Orchidaceae).
AB  - Germination of orchid seeds fully depends on a symbiotic association with soil
      borne fungi, usually Rhizoctonia spp. In contrast to the peaceful symbiotic
      associations between many other terrestrial plants and mycorrhizal fungi, this
      association is a life-and-death struggle. The fungi always try to invade the
      cytoplasm of orchid cells to obtain nutritional compounds. On the other hand, the
      orchid cells restrict the growth of the infecting hyphae and obtain nutrition by
      digesting them. It is likely that antifungal compounds are involved in the
      restriction of fungal growth. Two antifungal compounds, lusianthrin and chrysin,
      were isolated from the seedlings of Cypripedium macranthos var. rebunense that
      had developed shoots. The former had a slightly stronger antifungal activity than
      the latter, and the antifungal spectra of these compounds were relatively
      specific to the nonpathogenic Rhizoctonia spp. The level of lusianthrin, which
      was very low in aseptic protocorm-like bodies, dramatically increased following
      infection with the symbiotic fungus. In contrast, chrysin was not detected in
      infected protocorm-like bodies. These results suggest that orchid plants equip
      multiple antifungal compounds and use them at specific developmental stages;
      lusianthrin maintains the perilous symbiotic association for germination and
      chrysin helps to protect adult plants.

PMID- 17445847
TI  - [Unusual tumor in a 3 month-old baby].

PMID- 17445848
TI  - [Mandibular aneurysmal bone cyst mimicking a malignant tumor].
AB  - CASE: We report the case of a 24-year-old woman presenting with a rapidly growing
      mass in the right masseteric region. MRI suggested a diagnosis of a
      rhabdomyosarcoma but CT-scan evoked a benign lesion such as chondroblastoma or
      aneurismal bone cyst. The biopsy specimen proved the diagnosis of aneurismal bone
      cyst and the patient was treated by surgical curettage. There was no recurrence
      after 4 years of follow-up. DISCUSSION: The aneurismal bone cyst of the jaw is a
      rare pseudocystic lesion, characterized by replacement of the normal bone with
      fibro-osseous tissue containing blood-filled sinusoidal or cavernous spaces. The
      lesion generally affects young persons under 20 years of age. The molar region,
      the angle, and the ascending ramus of the mandible are the predominantly affected
      sites. The lesion does not have any clinical or radiological specificity and
      surgical curettage is the standard treatment. Recurrence is rare and occurs
      within 30 months after surgery.

PMID- 17445849
TI  - [Tooth extraction and anticoagulants].
AB  - INTRODUCTION: The purpose of this study was to show the possibility of extracting
      teeth without modifying the anticoagulant treatment (anti-platelet and anti
      vitamin K agents). MATERIAL AND METHOD: Two hundred patients underwent dental
      extraction from May 2003 to July 2006 without modifying their anticoagulant
      treatment; only 137 of them were hospitalized. Most of the teeth were extracted
      under local anesthesia, and hemostatic pad were inserted in the sockets without
      suture. RESULTS: One thousand (and) sixteen extractions were performed with
      bleeding disorders in 4%, successfully resolved by using local hemostatics.
      DISCUSSION: Modifying an anticoagulant treatment is a thrombo-embolic
      complication risk factor. Performing tooth extraction according to our protocol
      decreases this risk and bleeding complications, thus proving the validity of our
      technique.

PMID- 17445850
TI  - Semi-quantitative detection of Mycobacterium leprae antigens in skin scrapings:
      suitability as a laboratory aid for field diagnosis of leprosy.
AB  - We describe here a method, potentially suitable for field applications, for semi
      quantitative detection of Mycobacterium leprae antigens in skin scrapings, which
      are taken normally for smear microscopy. Thirty acid-fast bacilli-negative
      paucibacillary (PB) leprosy patients comprised the main study group; eight acid
      fast bacilli-positive multibacillary (MB) patients and five healthy laboratory
      workers served as controls. Samples in saline were spotted on nitrocellulose
      paper and probed with mycobacterium-specific polyclonal or M. leprae-specific
      mAbs against 12, 35 and 65kDa protein antigens, using a dot-ELISA format. Spot
      densities were read through a densitometer and also graded visually. The
      polyclonal antibody produced the best sensitivity, resulting in densitometric
      detection of mycobacterial antigen in 100% MB, 76% multiple-lesion PB and 62%
      single-lesion PB patients. None of the healthy volunteers showed antigen
      positivity. A correlation was noted between the densitometric and visual
      estimates of the antigen. Determination of antigen in the lesion and an
      apparently uninvolved area of skin in a subset of PB patients provided clues to
      the state of the underlying infection. Serological positivity of PB patients for
      M. leprae-specific antibodies against the 35kDa and phenolic glycolipid-I
      antigens was too low (<20%) for any diagnostic significance.

PMID- 17445851
TI  - Immunoglobulin (Ig)-containing plasma cells in the Harderian gland in broiler and
      native chickens of Bangladesh.
AB  - The distribution and frequency of immunoglobulin (Ig)-containing plasma cells,
      their variations due to sex, and the mode of secretion of Ig cells into the duct
      system of the Harderian gland was investigated in broiler and native chickens of
      both sexes in Bangladesh. The Harderian gland is covered by a capsule, and the
      connective tissue septa divide the gland into numerous unequal-sized numerous
      lobes and lobules. The Ig-containing plasma cells were located in the
      interstitial space, interacinar space, apical part of the lobule, and lumina of
      the lobules of the Harderian gland in both broiler and native chickens. The
      population of these Ig-containing plasma cells varied in between broiler and
      native chickens, and also between male and female broiler and native chickens. In
      the broiler, the number of IgM-containing plasma cells was higher; in contrast,
      in the native chickens, the population of IgA-containing plasma cells was larger.
      In the broiler, there were more IgA- and IgG-containing plasma cells in the male;
      in contrast, there were more IgM-containing plasma cells in female. In native
      chickens the frequency of IgA-containing plasma cells was greater in the female
      than male. When the data for broiler and native birds were compared, it was found
      that there were significantly more IgA- and IgG-containing plasma cells in the
      native male and female chickens than in the broiler males and females. The
      secretory Igs were located in the lumina of acini and the duct system of the
      Harderian gland. In the present study Ig-containing plasma cells were observed to
      be released in the lumina of the lobules of Harderian gland by the breakdown of
      acinar tissues in broilers, and by holocrine mode of secretion in the native
      chicken. These results suggested that the Harderian gland, even though it is not
      a lymphoid organ as a whole, but acts as an immunopotent organ in chickens, and
      that the gland in native chicken contains more Ig-containing plasma cells due to
      their scavenging.

PMID- 17445852
TI  - Exposure in utero to 2,2',3,3',4,6'-hexachlorobiphenyl (PCB 132) impairs sperm
      function and alters testicular apoptosis-related gene expression in rat
      offspring.
AB  - Toxicity of the polychlorinated biphenyls (PCBs) depends on their molecular
      structure. Mechanisms by prenatal exposure to a non-dioxin-like PCB,
      2,2',3,4',5',6-hexachlorobiphenyl (PCB 132) that may act on reproductive pathways
      in male offspring are relatively unknown. The purpose was to determine whether
      epididymal sperm function and expression of apoptosis-related genes were induced
      or inhibited by prenatal exposure to PCB 132. Pregnant rats were treated with a
      single dose of PCB 132 at 1 or 10 mg/kg on gestational day 15. Male offspring
      were killed and the epididymal sperm counts, motility, velocity, reactive oxygen
      species (ROS) generation, sperm-oocyte penetration rate (SOPR), testicular
      histopathology, apoptosis-related gene expression and caspase activation were
      assessed on postnatal day 84. Prenatal exposure to PCB 132 with a single dose of
      1 or 10 mg/kg decreased cauda epididymal weight, epididymal sperm count and
      motile epididymal sperm count in adult offspring. The spermatozoa of PCB 132
      exposed offspring produced significantly higher levels of ROS than the controls;
      ROS induction and SOPR reduction were dose-related. In the low-dose PCB 132
      group, p53 was significantly induced and caspase-3 was inhibited. In the high
      dose group, activation of caspase-3 and -9 was significantly increased, while the
      expressions of Fas, Bax, bcl-2, and p53 genes were significantly decreased. Gene
      expression and caspase activation data may provide insight into the mechanisms by
      which exposure to low-dose or high-dose PCB 132 affects reproduction in male
      offspring in rats. Because the doses of PCB 132 administered to the dams were
      approximately 625-fold in low-dose group and 6250-fold higher in high-dose group
      than the concentration in human tissue levels, the concentrations are not
      biologically or environmentally relevant. Further studies using environmentally
      relevant doses are needed for hazard identification.

PMID- 17445853
TI  - Basal and 3,3',4,4',5-pentachlorobiphenyl-induced expression of cytochrome P450
      1A, 1B and 1C genes in zebrafish.
AB  - The cytochrome P4501C (CYP1C) gene subfamily was recently discovered in fish, and
      zebrafish (Danio rerio) CYP1C1 transcript has been cloned. Here we cloned the
      paralogous CYP1C2, showing that the amino acid sequence is 78% identical to
      CYP1C1, and examined gene structure and expression of CYP1A, CYP1B1, CYP1C1, and
      CYP1C2. Xenobiotic response elements were observed upstream of the coding regions
      in all four genes. Zebrafish adults and embryos were exposed (24 h) to 100 nM
      3,3',4,4',5-polychlorinated biphenyl (PCB126) or 20 ppm acetone and subsequently
      held in clean water for 24 h (adults) or 48 h (embryos). All adult organs
      examined (eye, gill, heart, liver, kidney, brain, gut, and gonads) and embryos
      showed basal expression of the four genes. CYP1A was most strongly expressed in
      liver, whereas CYP1B1, CYP1C1, and CYP1C2 were most strongly expressed in heart
      and eye. CYP1B1 and the CYP1C genes showed an expression pattern similar to one
      another and to mammalian CYP1B1. In embryos CYP1C1 and CYP1C2 tended to have a
      higher basal expression than CYP1A and CYP1B1. PCB126 induced CYP1A in all
      organs, and CYP1B1 and CYP1C1 in all organs except gonads, or gonads and brain,
      respectively. CYP1C2 induction was significant only in the liver. However, in
      embryos all four genes were induced strongly by PCB126. The results are
      consistent with CYP1C1 and CYP1C2, as well as CYP1A and CYP1B1, being regulated
      by the aryl hydrocarbon receptor. While CYP1A may have a protective role against
      AHR agonists in liver and gut, CYP1B1, CYP1C1, and CYP1C2 may also play
      endogenous roles in eye and heart and possibly other organs, as well as during
      development.

PMID- 17445854
TI  - ERK-dependent and -independent pathways trigger human neural progenitor cell
      migration.
AB  - Besides differentiation and apoptosis, cell migration is a basic process in brain
      development in which neural cells migrate several centimeters within the
      developing brain before reaching their proper positions and forming the right
      connections. For identifying signaling events that control neural migration and
      are therefore potential targets of chemicals to disturb normal brain development,
      we developed a human neurosphere-based migration assay based on normal human
      neural progenitor (NHNP) cells, in which the distance is measured that cells
      wander over time. Applying this assay, we investigated the role of the
      extracellular signal-regulated kinases 1 and 2 (ERK1/2) in the regulation of NHNP
      cell migration. Exposure to model substances like ethanol or phorbol 12-myristate
      13-acetate (PMA) revealed a correlation between ERK1/2 activation and cell
      migration. The participation of phospho-(P-) ERK1/2 was confirmed by exposure of
      the cells to the MEK inhibitor PD98059, which directly prohibits ERK1/2
      phosphorylation and inhibited cell migration. We identified protein kinase C
      (PKC) and epidermal growth factor receptor (EGFR) as upstream signaling kinases
      governing ERK1/2 activation, thereby controlling NHNP cell migration.
      Additionally, treatments with src kinase inhibitors led to a diminished cell
      migration without affecting ERK1/2 phosphorylation. Based on these results, we
      postulate that migration of NHNP cells is controlled via ERK1/2-dependent and 
      independent pathways.

PMID- 17445855
TI  - Foot-and-mouth disease virus infection induces proteolytic cleavage of PTB,
      eIF3a,b, and PABP RNA-binding proteins.
AB  - Foot-and-mouth disease virus (FMDV) infection induces major changes in the host
      cell including the shutoff of cellular protein synthesis. Here, protein extracts
      from FMDV-infected cells have been used to monitor changes in the profile of RNA
      binding factors interacting with regulatory regions of the viral RNA. Relevant
      differences have been detected in the pattern of interaction with proteins
      prepared from either infected or uninfected cells with RNA probes encompassing
      the internal ribosome entry site (IRES), the 5' and 3'end regions. The binding
      patterns obtained for two divergent FMDV isolates showed differences depending on
      the viral isolate used. The identity of the host proteins giving a shifted
      binding pattern to RNA regulatory regions has been inferred by immunoblotting.
      Our results show that polypyrimidine tract-binding protein (PTB) and two subunits
      of translation initiation factor eIF3 interacting with the IRES undergo
      proteolytic processing during FMDV infection. In addition, poly(A)-binding
      protein (PABP), interacting with the 3'end of the viral RNA is partially
      processed. Proteolysis of eIF3a, eIF3b, PABP and PTB correlated with the extent
      of cytopathic effect induced by FMDV in infected cells.

PMID- 17445856
TI  - Recombination in feline immunodeficiency virus genomes from naturally infected
      cougars.
AB  - Recombination contributes significantly to diversity within virus populations and
      ultimately to viral evolution. Here we use a recently developed statistical test
      to perform exploratory analysis of recombination in fourteen feline
      immunodeficiency virus (FIVpco) genomes derived from a wild population of
      cougars. We use both the global and local Phi statistical test as an overall
      guide to predict where recombination may have occurred. Further analyses,
      including similarity plots and phylogenetic incongruence tests, confirmed that
      three FIVpco lineages were derived from recombinant events. Interestingly, the
      regions of mosaic origin were clustered in the area encoding lentiviral accessory
      genes and largely spared the viral structural genes. Because some of the mosaic
      strains are currently geographically disparate, our data indicate that the
      dispersal of cougars infected with these strains was preceded by recombination
      events. These results suggest that recombination has played an important role in
      the evolution of FIVpco for this wild population of cougars.

PMID- 17445857
TI  - Spatial facilitation is involved in flash-lag effect.
AB  - The flash-lag effect (FLE) is the perceptual phenomenon in which a flash adjacent
      to a continuously moving object is perceived behind it. Horizontal propagation of
      activity could explain a shorter latency for moving than for flashed objects but,
      to our knowledge, no psychophysical data supporting this has been given. We show
      that two concurrent moving stimuli increase the FLE, presumably due to a latency
      decrease in movement perception. Our results support the idea that spatial
      facilitation along the trajectory of a moving object reduces movement perception
      delay and, therefore, sustains an involvement of latency differences in FLE
      generation.

PMID- 17445858
TI  - An internal clock for predictive saccades is established identically by auditory
      or visual information.
AB  - Previously we have shown that repetitive predictive saccades to alternating
      visual targets are mediated by an internal clock. That is, when subjects track a
      periodic visual stimulus alternating at a high rate (a small inter-stimulus
      interval, ISI, of 500 or 833 ms), they use an internal estimate of stimulus
      timing to pre-program the eye movement timing. Auditory pacing tones at the same
      rate also generate predictive saccades. It is natural to ask if an identical
      internal clock is used to generate the predictive saccades in each case. We
      hypothesized that if subjects can use auditory information to establish an
      internal estimate of stimulus timing--as we demonstrated can be done with visual
      targets--then the distributions of predictive inter-saccade intervals should
      demonstrate the well-known "Scalar Property" for either Auditory Cued or Visual
      Cued stimuli: inter-saccade interval histograms should be almost identical when
      each is divided by its mean. However, when making reactive saccades to a pacing
      stimulus (at a low rate), there should be a difference in the timing statistics
      between Auditory and Visual pacing, due to differences in sensory processing. We
      report here that the variances of inter-saccade intervals at three predictive
      pacing rates (ISIs of 500, 833, and 1000 ms) are equivalent, whereas the variance
      for Auditory Cued Pacing was greater than that for Visual Cued Pacing during
      reactive saccades at two reactive pacing rates (ISIs of 1667 and 2500 ms). When
      the inter-saccade interval histograms at the predictive pacing rates were
      normalized, the distributions were nearly identical for both Visual and Auditory
      Cued Pacing, which means that the Scalar Property holds for predictive saccades
      from either pacing stimulus. These results suggest that (1) an internal timing
      reference (clock) can be established by either auditory or visual information and
      (2) during predictive tracking the variability in saccade timing is due to the
      variability in the internal timing representation, while during reactive tracking
      the variability in saccade timing depends on the sensory modality used to trigger
      the saccades.

PMID- 17445859
TI  - Effects of spatial attention and salience cues on chromatic and achromatic motion
      processing.
AB  - While several previous psychophysical and neurophysiological studies have
      demonstrated chromatic (red/green) input to motion processing, the nature of this
      input is still a matter of debate. In particular, there exists controversy as to
      whether chromatic motion processing is mediated by low-level motion mechanisms
      versus higher-level, attention- or salience-based mechanisms. To address the role
      of attention, in Experiment 1, we asked whether spatial attention exerts larger
      effects on chromatic (red/green), as compared to achromatic, motion. To this end,
      we employed a motion after-effect (MAE) paradigm, and measured attention effects
      by comparing MAE duration between conditions where subjects attended to the
      adapting moving grating stimulus versus ignored that stimulus because they were
      required to perform an attentionally demanding vowel detection task at the center
      of gaze. The results from these experiments revealed equal effects of spatial
      attention on chromatic and achromatic motion processing, which were essentially
      constant (roughly 1.4-fold) across a wide range of stimulus contrasts (3.2-25%
      cone contrast). These findings suggest that chromatic motion processing is not
      affected disproportionally by higher-level spatial attention mechanisms. To
      address the role of salience, in Experiment 2, we investigated the effects of
      bottom-up salience cues on the strength of chromatic and achromatic motion, as
      measured with the MAE. Salience was manipulated by varying the relationship
      between the moving gratings and the background color. The results of these
      experiments revealed small and insignificant effects of salience cues on
      chromatic and achromatic motion processing. These findings suggest that
      mechanisms sensitive to feature salience do not influence low-level chromatic
      motion mechanisms mediating the motion after-effect.

PMID- 17445860
TI  - Microbial impact of small tributaries on water and shellfish quality in shallow
      coastal areas.
AB  - This study aimed to investigate the impact of small tributaries on seawater and
      shellfish quality in coastal area subjected to brief episodes leading to fecal
      contamination. Escherichia coli and F-RNA-specific bacteriophages were selected
      as fecal indicators and astroviruses were chosen as being representative of
      pathogens in the human population during winter viral epidemics. A two
      dimensional hydrodynamic model was built to simulate the current and dispersion
      in the model domain, which includes areas uncovered at low tide. The model also
      includes decay rates to simulate microorganism behavior and assess the influence
      of fecal input on shellfish quality. The originality lies in the fact that
      specific features of the study area were considered. Modeling results indicate
      limited particle movements and long flushing times at the back of the bay, where
      shellfish are farmed. Computational results showed that under normal conditions,
      i.e. 94% of the time, when rainfall was less than 10 mm per day, the sector shows
      acceptable water quality. These results are in agreement with shellfish
      concentration measured in the field. Under high flow conditions, high
      concentrations of fecal indicators and astrovirus were measured in the river and
      tributaries. The corresponding fluxes were over 50 times higher than under normal
      weather conditions. The location of the shellfish beds near the coast makes them
      vulnerable and fecal indicators and viruses were detected in shellfish after
      short rainfall events. Our modeling approach makes a contribution to shellfish
      management and consumer protection, by indicating the "risk period" as defined by
      EU regulations. Molecular development such as viral quantification in conjunction
      with model developments will help to prevent shellfish contamination and thus
      provide safer products to consumers and an effective tool for shellfish
      producers.

PMID- 17445861
TI  - Evidence for flocculation in glacier-fed Lillooet Lake, British Columbia.
AB  - This study provides evidence of in situ flocculation in a glacier-fed freshwater
      lake. Direct observation of flocculated particles using microscopy provides the
      strongest evidence to establish that clastic suspended sediment in Lillooet Lake
      is flocculated. Flocs in Lillooet Lake exhibit a hierarchical size structure,
      with primary particles (<4 microm) joining to create microflocs (10-35 microm),
      and both primary particles and microflocs joining to create macroflocs (200-280
      microm). In situ laser particle sizing reveals primary particles and microflocs
      dominate in the epilimnion, a zone susceptible to shear induced by wind or inflow
      and exhibiting the highest suspended sediment loads. Macroflocs dominate in the
      hypolimnion, a more quiescent zone and exhibiting the lowest suspended sediment
      loads. Flocculated particles are invisible to traditional methods of sediment
      analysis in glaciolacustrine settings. Flocculation is a plausible explanation
      for accelerated sedimentation of the clay-sized sediments known to dominate the
      size distribution of varves in other glacier-fed lakes.

PMID- 17445862
TI  - Uptake of Zn2+ ions by a fully iron-exchanged clinoptilolite. Case study of
      heavily contaminated drinking water samples.
AB  - Clinoptilolite, a natural zeolite, was used for the synthesis of a high surface
      area clinoptilolite (Clin)-iron (Fe) oxide system, in order to be used for the
      removal of Zn(2+) ions from drinking water samples. The new system was obtained
      by adding natural Clin in an iron nitrate solution under strongly basic
      conditions. The Clin-Fe system has specific surface area equal to 151 m(2)/g and
      is fully iron exchanged (Fe/Al=1.23). Batch adsorption experiments were carried
      out to determine the effectiveness of the Clin and the Clin-Fe system in removal
      of Zn from drinking water. Adsorption experiments were conducted by mixing 1.00 g
      of each of the substrates with certain volume of water samples contaminated with
      ten different Zn concentrations (from 7.65x10(-5) to 3.82x10(-2)M or from 5.00 to
      2500 ppm Zn). For our experimental conditions, the maximum adsorbed Zn amount by
      Clin was 71.3mg/g, whereas by the Clin-Fe system 94.8 mg/g. The main factors that
      contribute to different adsorbed Zn amounts by the two solids are due to new
      surface species and negative charge of the Clin-Fe system. In addition, the
      release of counterbalanced ions (i.e. Ca(2+), Mg(2+), Na(+) and K(+)) was
      examined, as well as the dissolution of framework Si and Al. It was found that
      for most of the samples the Clin-Fe system releases lower concentrations of Ca,
      Mg and Na and higher concentrations of K than Clin, while the dissolution of
      Si/Al was limited. Changes in the composition of water samples, as well as in
      their pH and conductivities values were reported and explained.

PMID- 17445863
TI  - Struvite crystallisation and recovery using a stainless steel structure as a seed
      material.
AB  - A metallic system acting as a seed substrate has been designed and developed in
      order to assess its efficiency in recovering phosphorus as struvite. The device,
      consisting of two concentric stainless steel meshes, was immerged in the upper
      section of a pilot crystallisation reactor fed with synthetic liquors (MgCl(2) x
      6H(2)O, NH(4)H(2)PO(4),) for 2h. Apart from soluble PO(4)-P removals which
      remained in the range 79-80% with or without application of the metallic system,
      it was found that under the specific operating conditions tested the meshes were
      capable of accumulating struvite at a rate of 7.6 gm(-2)h(-1), hence reducing
      significantly the amount of fine particles remaining in solution from 302.2 to 12
      mg L(-1) when compared to trials without mesh.

PMID- 17445864
TI  - The organic carbon derived from sewage sludge as a key parameter determining the
      fate of trace metals.
AB  - In a sandy agricultural soil of south-west of France, continuously cultivated
      with maize and amended with sewage-sludge over 20 years, the behavior of three
      trace metals (Cu, Pb, and Zn) was studied during the sludge applications (1974
      1993) and after its cessation (1993-1998). Using the delta13C analysis, the
      dynamics of different sources of organic matter were followed in order to
      elucidate the influence of the sludge-derived organic matter on the fate of trace
      metals in the soil and its particle size fractions. This study revealed that
      sludge-derived organic matter contributed to the formation of macroaggregates
      through the binding of preexisting microaggregates. These macroagreggates were
      thus responsible for the accumulation of trace metals in the coarsest fraction as
      well as for the protection of maize-derived organic matter against
      biodegradation. After sludge application ceased, the disaggregation of
      macroaggregates occurred simultaneously with high losses in Cu and Pb. On the
      contrary, Zn appeared less affected by the cessation of sludge application, with
      only a location change from coarse to fine fractions.

PMID- 17445865
TI  - Effects of Cadmium and Zinc on the feeding behaviour of two freshwater
      crustaceans: Atyaephyra desmarestii (Decapoda) and Echinogammarus meridionalis
      (Amphipoda).
AB  - Lethal and sublethal effects of Cadmium and Zinc on two freshwater crustaceans
      were investigated. The 96-h LC50 for Cadmium and Zinc were 42.20 microg l(-1) and
      5.43 mg l(-1) for Atyaephyra desmarestii, and 36.17 microg l(-1) and 4.61 mg l(
      1) for Echinogammarus meridionalis, respectively. An increase in metal
      concentrations at sublethal levels resulted in significant reductions of the
      feeding rate of both species. The LOECs in the chronic feeding assays for Zinc
      were 1.29 mg l(-1) for A. desmarestii and 0.4 mg l(-1) for E. meridionalis. For
      Cadmium the LOEC was 6.53 microgl(-1) for both species. The results suggest the
      potential use of these two crustacean species as test organisms in
      ecotoxicological tests. Feeding assays appear to be a rapid, cheap and effective
      tool to be used in biomonitoring studies of Portuguese freshwaters.

PMID- 17445866
TI  - Photocatalysis of fluorene adsorbed onto TiO2.
AB  - The adsorption of fluorene onto TiO2 has been investigated by conducting
      equilibrium and kinetic experiments. Adsorption isotherms have been evaluated at
      two different pHs in the range of temperatures 296-325 K. The type III isotherm
      shapes obtained were modelled by considering several expressions taken from the
      literature. Temperature exerted a positive influence in fluorene uptake. Addition
      of phosphates involved a negative effect when computing the final equilibrium
      fluorene removal. The kinetic experiments carried out at 296 K corroborated the
      competitiveness of phosphates to occupy the active sites on the titania surface.
      Nevertheless, equilibrium conditions are faster achieved at pH 2 than at pH 5.
      The photocatalysis of fluorene at different initial concentrations of the parent
      compound revealed a slight improvement of the process at pH 5 if compared to the
      results obtained at pH 2. A Langmuir-Hinselwood representation of the data
      confirms the previous statement. Catalyst load shows an optimum, concentration
      values of the photocatalyst above the optimum provoke a decrease in the fluorene
      abatement rate. Reutilisation of the catalyst indicates that fluorene is
      completely eliminated from the solid, i.e. it is suggested that fluorene and
      intermediates are surface oxidised.

PMID- 17445867
TI  - Endothelin-3 growth factor levels decreased in cervical cancer compared with
      normal cervical epithelial cells.
AB  - We used cDNA microarray analysis of RNA extracted from normal, dysplastic, and
      cancerous cervical tissues to identify the changes in gene expression during the
      procession from normal to cancerous cervical epithelial cells. We found the
      expression of 5 genes in cancerous cervical epithelial cells that were not found
      in normal cervical epithelial cells, among which were lymphoid-restricted
      membrane protein, protease serine 2, WD repeat domain 59, thyrotropin-releasing
      hormone degrading enzyme, and the endothelin-3 growth factor. We then analyzed
      the expression levels of endothelin growth factors 1, 2, and 3 (ET-1, ET-2, and
      ET-3) and their receptors A and B (ETR-A and ETR-B) by reverse transcriptase
      polymerase chain reaction in 3 cervical cancer cell lines and by
      immunohistochemical staining in cervical normal, dysplastic, and cancer tissues.
      ET-1, ET-2, and ET-3 growth factor levels were detectable in the maturing layer
      of cervical epithelium but not in the germinal layer. All 3 growth factors (ET-1,
      ET-2, and ET-3) were detected in the cytoplasm of the maturing normal cervical
      epithelial cells. In addition, there were decreased levels of ET-3 and increased
      levels of ET-1, ET-2, ETR-A, and ETR-B in cancerous cervical epithelial cells
      compared with normal cervical epithelial cells. These results suggest that the
      reduction of ET-3 growth factor levels may be important in the transition from
      normal to cancerous cervical epithelium.

PMID- 17445868
TI  - Differences in the aerosolization behavior of microorganisms as revealed through
      their transport by biogas.
AB  - The aerosol microbial diversity of biogas was analyzed in order to examine the
      aerosolization behavior of microorganisms. Six biogas samples were analyzed: five
      from mesophilic and thermophilic anaerobic digestors treating different wastes,
      and one from landfill. Epifluorescent microscopic counts reveal that with 10(6)
      Prokarya m(-3), only one per one thousand billion were aerosolized from the
      digestor sludges to the biogas. SSU (Small Sub Unit) ribosomal fingerprinting
      (Single Strand Conformation Polymorphism) shows that microbial communities in the
      biogas were not just a rough copy of anaerobic digestor microbial communities and
      underlines that all microorganisms are not equally convoyed by biogas. To assess
      the difference occurring in aerosolization, 675 biogas-borne SSU ribosomal DNA
      were analyzed and compared to published anaerobic digestor microbial diversity.
      Results show that microorganisms belonging to Archaea, Deltaproteobacteria,
      Spirochaetes, Thermotogae, Chloroflexi phyla and sulfate-reducing groups were non
      aerosolized whereas microorganisms belonging to Alphaproteobacteria,
      Betaproteobacteria, Gammaproteobacteria, TM7 phyla as well as strictly aerobic
      and occasionally pathogenic species presented high levels of aerosolization.
      Finally, microorganisms belonging to Actinobacteria, Firmicutes and Bacteroidetes
      phyla represent passively-aerosolized microorganisms with similar frequencies in
      biogas-borne and anaerobic digestor microbial communities.

PMID- 17445869
TI  - Adverse effects of organic arsenical compounds towards Vibrio fischeri bacteria.
AB  - The most frequently encountered forms of organic arsenic, namely, dimethylarsinic
      acid, monomethylarsonic acid, arsenobetaine, arsenocholine and Roxarsone (4
      hydroxy-3-nitrobenzene arsonic acid) were tested for toxicity either by using the
      Microtox bioassay, based on the rapid (within 15 min) fading of luminescence
      emitted by Vibrio fischeri marine bacteria, or by monitoring growth rate of the
      same bacteria for 3 days. Organic arsenic was generally found to be less toxic to
      these biological models than inorganic arsenic. In many cases, EC50 values for
      DMA, MMA or HNAA when using luminescence or growth inhibition assays could not be
      determined because of the low toxicity of the compounds. Nevertheless, results
      from the luminescence inhibition assay, which was found to be more sensitive than
      the growth inhibition assay, allowed to rank toxicity as follows: arsenate at pH
      8>HNAA at pH 5>arsenate at pH 5>MMA at pH 5>HNAA at pH 8>DMA at pH 5.
      Arsenobetaine and monomethylarsonic acid were unexpectedly found to stimulate
      bacterial growth (hormesis effect). pH was found to have a strong influence on
      the observed toxicity as a consequence of the pH-induced changes in the chemical
      speciation of the tested molecules. In most cases it appeared that negatively
      charged forms were less toxic than the uncharged ones.

PMID- 17445870
TI  - AGEs and methylglyoxal induce apoptosis and expression of Mac-1 on neutrophils
      resulting in platelet-neutrophil aggregation.
AB  - INTRODUCTION: Diabetes mellitus is characterised by hyperglycaemia that plays an
      important role in the pathogenesis of diabetic complications including
      accumulation of methylglyoxal (MG), a highly reactive alpha-dicarbonyl metabolite
      of glucose degradation pathways and increased generation of advanced glycation
      end products (AGEs). The aim of this study was to investigate the impact of AGE
      BSA, the model substance for AGEs, and MG on cellular haemostasis. MATERIALS AND
      METHODS: Isolated peripheral blood mononuclear cells (PBMCs) or whole blood was
      incubated with AGE-BSA and MG. Markers of cellular haemostasis were monitored by
      flow cytometry. RESULTS: Exposure of PBMCs to AGE-BSA and MG resulted in a dose-
      and time-dependent increase of TF-expression by monocytes. AGE-BSA and MG induced
      enhanced platelet-neutrophil aggregation. Examination of platelet activation
      showed that AGE-BSA induces no direct effect on the expression of P-selectin.
      However, stimulation with MG resulted in a dose-dependent expression of P
      selectin by platelets. Stimulation with AGE-BSA or MG markedly increased dose
      dependent expression of Apo2.7 on the neutrophil mitochondria. In addition the
      analysis demonstrated for the first time that both AGE-BSA and MG induce a dose
      dependent expression of the adhesion molecule Mac-1 on the surface of
      neutrophils. CONCLUSIONS: AGE-BSA as well as MG induced apoptosis of neutrophils
      and enhanced expression of the adhesion molecule Mac-1 resulting in increased
      formation of platelet-neutrophil aggregates. These findings may contribute to
      better understand the mechanism of diabetic thrombosis and the associated high
      cardiovascular risk of diabetic patients.

PMID- 17445871
TI  - The fibrinogen gamma (FGG) 10034C>T polymorphism is associated with venous
      thrombosis.
AB  - INTRODUCTION: Thrombin-induced conversion of fibrinogen to fibrin plays an
      essential role in hemostasis and results in the stabilization of thrombi.
      Elevated plasma fibrinogen levels have been associated with both increased plasma
      viscosity and platelet aggregability. Recently, a haplotype-tagging single
      nucleotide polymorphism characterized by a C to T substitution at nucleotide
      10034 of the fibrinogen gamma gene (FGG 10034C>T, rs2066865), has been proposed
      as a novel risk factor for deep venous thrombosis (DVT). Aim of the present study
      was to provide further data on the role of the FGG 10034C>T polymorphism for DVT.
      MATERIALS AND METHODS: FGG genotypes were determined by 5'-exonuclease assay
      (TaqMan) in 358 patients with documented DVT and a total of 783 control subjects.
      RESULTS: In a multivariate analysis adjusting for age, sex, presence of factor V
      Leiden and carriage of prothrombin 20210A, homozygosity for the FGG 10034 TT
      genotype yielded an odds ratio of 2.01 (95% CI 1.23-3.31; p=0.006) for DVT.
      CONCLUSIONS: Our data confirm the primary finding that the FGG 10034C>T
      polymorphism is associated with DVT risk.

PMID- 17445872
TI  - Wnt pathway-related gene expression during malignant progression in ulcerative
      colitis.
AB  - Long-standing ulcerative colitis (UC) has been associated with a high risk of
      developing colonic adenocarcinoma. Importantly, both low- and high-grade
      dysplasia are strongly related to the presence or development of malignancy. The
      canonical Wnt/beta-catenin signaling pathway is of crucial importance in cancer
      development and progression, but its role in UC-related carcinogenesis remains to
      be determined. We evaluated the immunolabeling patterns of beta-catenin, as well
      as the products of Wnt-associated cancer genes E-cadherin, cyclin D1 and c-myc,
      along the dysplasia-carcinoma pathway in UC. For this purpose,
      immunohistochemistry (IHC) was performed on 18 adenocarcinomas and 17 dysplasias,
      derived from 21 patients. We found that intracellular beta-catenin accumulation,
      the hallmark of Wnt signaling activation, is observed in dysplasia, together with
      enhanced labeling of nuclear protein cyclin D1 and reduction of membranous
      labeling of E-cadherin. c-myc displayed moderate immunolabeling in the
      (pre)malignant lesions. Thus, the Wnt pathway is activated in early stages of
      malignant progression in UC. Furthermore, upregulation of the oncogene cyclin D1
      and downregulation of tumor suppressor E-cadherin also occurs in the
      (pre)neoplastic state. This may contribute to the high potential for malignant
      degeneration of dysplasia in UC-related colitis.

PMID- 17445873
TI  - Effects of the cannabinoid antagonist SR141716 (rimonabant) and d-amphetamine on
      palatable food and food pellet intake in non-human primates.
AB  - The purpose of this study was to determine if a cannabinoid CB(1) receptor
      antagonist would selectively decrease consumption of highly palatable food in non
      human primates. The CB(1) receptor antagonist SR141716 (rimonabant; 0.12-1.0
      mg/kg, i.m.) and the stimulant anorectic drug d-amphetamine (0.12-1.0 mg/kg,
      i.m.) were administered to non-food deprived baboons for the purpose of measuring
      the effect of each drug on consumption of the normal diet, and a large single
      meal of a high-carbohydrate candy. Four male and four female baboons had access
      to food 24 h each day, but they had to complete a two phase operant procedure in
      order to eat. Responding on one lever during a 30-min appetitive phase was
      required before animals could start a consumption phase, where responding on
      another lever led to food delivery, i.e., a meal. Three days a week baboons
      received a jelly sugar-coated candy (Skittles) during the first meal and then
      pellets were available in subsequent meals. All baboons ate as many individual
      candies in one meal as they did pellets throughout the entire day. Acute d
      amphetamine and, to a lesser extent, SR141716 decreased both candy intake in a
      single meal and pellet intake in a single meal and over 24 h. d-Amphetamine, but
      not SR141716, increased latency to the candy meal and the first pellet meal
      indicating that the two drugs differentially altered feeding topography. Although
      males ate more food pellets than females, few other sex differences were
      observed. Thus, although effective in decreasing food intake, there was no
      evidence of a specific effect of CB(1) receptor antagonism on consumption of a
      large meal or a palatable food.

PMID- 17445874
TI  - Blocking of conditioning to a cocaine-paired stimulus: testing the hypothesis
      that cocaine perpetually produces a signal of larger-than-expected reward.
AB  - According to a recent account of addiction, dopaminergic effects of drugs like
      cocaine mimic the neuronal signal that occurs when a natural reward has a larger
      value than expected. Consequently, the drug's expected reward value increases
      with each administration, leading to an over-selection of drug-seeking behavior.
      One prediction of this hypothesis is that the blocking effect, a cornerstone of
      contemporary learning theory, should not occur with drug reinforcers. To test
      this prediction, two groups of rats were trained to self-administer cocaine with
      a nose-poking response. For 5 sessions, a tone was paired with each self
      administered injection (blocking group), or no stimulus was paired with injection
      (non-blocking group). Then, in both groups, the tone and a light were both paired
      with each injection for 5 sessions. In subsequent testing, the light functioned
      as a conditioned reinforcer for a new response (lever-pressing) in the non
      blocking group, but not the blocking group. Thus, contrary to prediction, pre
      training with the tone blocked conditioning to the light. Although these results
      fail to support a potentially powerful explanation of addiction, they are
      consistent with the fact that most conditioning and learning phenomena that occur
      with non-drug reinforcers can also be demonstrated with drug reinforcers.

PMID- 17445875
TI  - CCR5 Delta 32 mutation, Mycoplasma pneumoniae infection, and asthma.

PMID- 17445876
TI  - Identification and characterization of a novel allergen from Blomia tropicalis:
      Blo t 21.
AB  - BACKGROUND: Allergenic components from Blomia tropicalis are important triggers
      of allergies in the tropics. OBJECTIVE: We sought to identify and characterize a
      novel allergen, Blo t 21, from B tropicalis. METHODS: Blo t 21 was initially
      identified from an expressed sequence tag database generated from a B tropicalis
      cDNA library. Allergenicity of this antigen was examined by means of skin prick
      testing, ELISA, and IgE immuno-dot blotting. We evaluated whether Blo t 21 and
      Blo t 5 were cross-reactive by using IgE inhibition ELISAs. RESULTS: Blo t 21, a
      129-amino-acid protein sharing 39% identity with Blo t 5, is a product of a
      single-copy gene. It has an alpha-helical secondary structure and localizes to
      midgut and hindgut contents of B tropicalis, as well as fecal particles. Positive
      responses to Blo t 21 were shown in 93% (40/43) by means of ELISA and 95% (41/43)
      by means of skin prick testing when assayed in 43 adult patients with ongoing
      persistent allergic rhinitis. However, sera of 494 consecutive individuals
      attending outpatient allergy clinics over 1(1/2) years showed 57.9% (286/494) had
      positive responses to Blo t 21. Although the majority (>75%) of sensitized
      individuals were cosensitized to both Blo t 5 and Blo t 21, these 2 allergens had
      a low-to-moderate degree of cross-reactivity. CONCLUSION: Blo t 21 is a major
      allergen in B tropicalis that is not highly cross-reactive to Blo t 5, despite
      sharing some sequence and structural identity. CLINICAL IMPLICATIONS: Blo t 21,
      representing a new group of allergens, is an important B tropicalis allergen.

PMID- 17445877
TI  - Vascular endothelial growth factor and plasminogen activator inhibitor-1 in
      children with recurrent early wheeze.

PMID- 17445878
TI  - Right hemisphere sensitivity to novel metaphoric relations: application of the
      signal detection theory.
AB  - The present study used the signal detection theory to test the hypothesis that
      the right hemisphere (RH) is more sensitive than the left hemisphere (LH) to the
      distant semantic relations in novel metaphoric expressions. In two divided visual
      field experiments, sensitivity (d') and criterion (beta) were calculated for
      responses to different types of word pairs. In the first experiment, subjects
      were presented with unfamiliar two-word novel metaphoric expressions ("signal")
      and unrelated word-pairs ("noise"). In the second experiment, literal expressions
      ("signal") and unrelated word pairs ("noise") were presented. In line with the
      Coarse Semantic Coding Theory [Beeman, M. (1998). Coarse semantic coding and
      discourse comprehension. In: M. Beeman & C. Chiarello (Eds.). Right hemisphere
      language comprehension: Perspectives from cognitive neuroscience. Mahwah, NJ:
      Erlbaum, pp. 255-284.] as well as with the Graded Salience Hypothesis [Giora, R.
      (2003). On our mind: Salience, context and figurative language. New York: Oxford
      University Press.], the findings suggest that the RH is more sensitive than the
      LH to unfamiliar metaphoric relations. Furthermore, this RH advantage in
      processing distant semantic relations did not extend to familiar semantic
      relations.

PMID- 17445879
TI  - Family developmental risk factors among adolescents with disabilities and
      children of parents with disabilities.
AB  - This paper investigates how the learning environments and family dynamics differ
      if households have a child with a disability or a parent with a disability. Using
      data from the National Longitudinal Survey of Youth 1997, results indicate that
      children with disabilities experience similar learning environments as other
      children, but have somewhat weaker relationships with their parents. In two
      parent families, maternal disability lowers parents' school involvement and is
      associated with a less enriching home environment. Paternal disability reduces
      maternal monitoring and positive family activities possibly because mothers
      divert care-giving resources from their children to their male partners. Children
      in mother-headed households experience learning environments and family dynamics
      that are similar regardless of their own disability status or that of their
      mothers, but these outcomes are markedly inferior to those of children growing up
      in two-parent households. Future research on adolescent development should
      consider the disability status of children and parents, with particular attention
      to patterns of gendered care-giving in American families.

PMID- 17445880
TI  - On imparting radiopacity to a poly(urethane urea).
AB  - A poly(urethane urea) (PUU) synthesized from 2,4-toluene diisocyanate (TDI) and
      polyethylene glycol (PEG) with ethylenediamine (ED) as the chain extender was
      rendered radiopaque by attaching 3,4,5-triiodobenzoic acid (TIB) onto the polymer
      backbone. The radiopaque polyurethane obtained was characterized by infra red
      (IR) spectroscopy, thermogravimetric analysis (TGA), differential scanning
      calorimetry (DSC) and X-radiography. By optimizing the reaction conditions, it
      was possible to carry out the modification without adversely affecting the
      properties of the starting polymer significantly. IR spectral evidence suggested
      that the hydrogen bonded structure of PUU remained undisrupted even after
      modification. However, the product exhibited altered thermal characteristics when
      compared to the parent polymer. Degradation characteristics as observed from the
      TGA remained unchanged, while one of the glass transitions got shifted to a lower
      temperature. The observed changes in thermal characteristics were explained on
      the basis of possible inter-phase mixing and the changes in the close packing of
      the polymer chains by the introduction of bulky iodine atoms.

PMID- 17445881
TI  - The effect of strontium incorporation into CaSiO3 ceramics on their physical and
      biological properties.
AB  - CaSiO3 ceramics have been regarded as a potential bioactive material for bone
      regeneration. Strontium (Sr) as a trace element in human body has been found to
      have beneficial effects on bone formation. The aim of this study was to
      incorporate Sr into CaSiO3 bioactive ceramics and to investigate their effect(s)
      on phase transition, sintering property, apatite-formation ability, ionic
      dissolution, and human bone-derived cells (HBDC) proliferation. Sr containing
      CaSiO3 (Sr-CaSiO3) ceramics at various concentrations (0-10% Sr) were prepared.
      The incorporation of Sr into CaSiO3 promoted the phase transition from beta to
      alpha-CaSiO3 and enhanced ceramic densification but did not alter the mechanism
      and ability of apatite formation in SBF. The ionic dissolution rate of the Sr
      CaSiO3 decreased compared to the CaSiO3. The addition of Sr decreased pH value in
      SBF. The effect of Sr-CaSiO3 extracts, carried out according to the International
      Standard Organization, on HBDC proliferation was evaluated. At high extract
      concentration (100 and 200 mg/mL), CaSiO3 was found to stimulate HBDC
      proliferation, however, the incorporation of Sr into CaSiO3 stimulated HBDC
      proliferation even at low extract concentration (ranging from 12.5, 25 to 50
      mg/mL). Our results indicate that Sr-CaSiO3 ceramics improved the physical and
      biological properties of the pure CaSiO3 ceramics.

PMID- 17445883
TI  - Functional consequences of activating store-operated CRAC channels.
AB  - Store-operated CRAC channels, which are activated by the emptying of the
      endoplasmic reticulum Ca(2+) stores, are an important and widespread route for
      triggering rises in cytoplasmic Ca(2+). The cellular responses that are activated
      in response to Ca(2+) entry through CRAC channels are being dissected out, and
      recent evidence has established that CRAC channels can induce both short-term
      (safeguarding the Ca(2+) content of the endoplasmic reticulum, maintenance of
      cytoplasmic Ca(2+) oscillations, enzyme activation, secretion) and long-term
      (gene expression) changes in cells. CRAC channel activation is therefore capable
      of evoking a range of temporally distinct responses, highlighting the versatility
      of this ubiquitous Ca(2+) entry pathway.

PMID- 17445882
TI  - Injectable biodegradable hydrogel composites for rabbit marrow mesenchymal stem
      cell and growth factor delivery for cartilage tissue engineering.
AB  - We investigated the development of an injectable, biodegradable hydrogel
      composite of oligo(poly(ethylene glycol) fumarate) (OPF) with encapsulated rabbit
      marrow mesenchymal stem cells (MSCs) and gelatin microparticles (MPs) loaded with
      transforming growth factor-beta1 (TGF-beta1) for cartilage tissue engineering
      applications. Rabbit MSCs and TGF-beta1-loaded MPs were mixed with OPF, a
      poly(ethylene glycol)-diacrylate crosslinker and the radical initiators ammonium
      persulfate and N,N,N',N'-tetramethylethylenediamine, and then crosslinked at 37
      degrees C for 8 min to form hydrogel composites. Three studies were conducted
      over 14 days in order to examine the effects of: (1) the composite formulation,
      (2) the MSC seeding density, and (3) the TGF-beta1 concentration on the
      chondrogenic differentiation of encapsulated rabbit MSCs. Bioassay results showed
      no significant difference in DNA amount between groups, however, groups with MPs
      had a significant increase in glycosaminoglycan content per DNA starting at day 7
      as compared to controls at day 0. Chondrocyte-specific gene expression of type II
      collagen and aggrecan were only evident in groups containing TGF-beta1-loaded MPs
      and varied with TGF-beta1 concentration in a dose-dependent manner. Specifically,
      type II collagen gene expression exhibited a 161+/-49-fold increase and aggrecan
      gene expression a 221+/-151-fold increase after 14 days with the highest dose of
      TGF-beta1 (16 ng/ml). These results indicate that encapsulated rabbit MSCs
      remained viable over the culture period and differentiated into chondrocyte-like
      cells, thus suggesting the potential of OPF composite hydrogels as part of a
      novel strategy for localized delivery of stem cells and bioactive molecules.

PMID- 17445884
TI  - Effect of acupuncture on pubertal development of rats and rabbits at different
      developmental stages.
AB  - Physiological and endocrine studies on sexual development in animals and effects
      of acupuncture on sexual development are limited. Therefore, we investigated the
      effect of electro-acupuncture (EA) on the arcuate nucleus (Arc) and release of
      gonadotropin-releasing hormone (GnRH) in animals at different developmental
      stages. In Experiment 1, EA stimulation (30 Hz) was performed for 30 min per day
      in EA group of rabbits for 48 days, while the control group (mature rabbits) was
      not given EA. Arc discharges in those two groups were measured after the 48-day
      treatment. Arc discharge was also measured in the pre-pubertal group (as control)
      without EA treatment. Then, all three groups were treated with transient EA for
      30 min and Arc discharges were determined again. In Experiment 2, EA (3 Hz) at
      the same acupoints or non-acupoints as that in the rabbits was performed for 20
      min per day in different developmental group of Sprague-Dawley rats for 10 days.
      GnRH mRNA expression in the hypothalamus of rats was determined using RT-PCR and
      real-time PCR. The serum sexual hormone, sperm count, and body weight was
      measured. The results showed that the Arc discharge (P<0.01), testosterone (T)
      (P<0.01) and sperm count (P<0.01) in male rabbits were reduced by repeated EA.
      However, the body weight of rabbits was not changed after EA compared to the
      control in Experiment 1. In Experiment 2, GnRH mRNA expression in rats of the
      early pubertal group (EPG) and adult group (AG) were significantly depressed
      after repeated EA at acupoints (P<0.01). The sexual hormones were negatively
      influenced by repeated EA during puberty. Sperm count was reduced significantly
      after repeated EA at time of puberty (P<0.01). Repeated EA did not influence body
      weight of rats (P>0.01) and structures of the gonadial tissues during
      development. The results suggested that repeated EA is a good option that can be
      considered for regulating the function of the hypothalamus-pituitary-gonad (HPG)
      axis during puberty.

PMID- 17445885
TI  - Comparison of minimal residual disease (MRD) estimated by flow cytometry and by
      real-time quantitative PCR of Wilms tumor gene 1 (WT1) transcript expression in
      children with acute lymphoblastic leukemia.
AB  - Minimal residual disease (MRD) in 56 children with acute lymphoblastic leukemia
      (ALL) was quantified simultaneously by flow cytometry and by RQ-PCR of WT1
      transcripts. Six patients failed remission induction, all had detectable MRD by
      flow cytometry, and two had undetectable MRD by WT1 assay. Among 41 patients, who
      achieved remission and had overexpression of WT1 transcripts at diagnosis, the
      two techniques gave concordant MRD results in 26 and discordant MRD results in
      15. Nine patients did not show overexpression of WT1 at diagnosis. Our results
      indicate that RQ-PCR measurements of WT1 may be of limited value for monitoring
      MRD in childhood ALL.

PMID- 17445886
TI  - Downregulation of c-Myc is critical for valproic acid-induced growth arrest and
      myeloid differentiation of acute myeloid leukemia.
AB  - Valproic acid (VPA), an agent used for neurological disorders, has been shown to
      be a novel class of histone deacetylase inhibitor (HDACI), able to induce
      apoptosis and myeloid differentiation of acute myeloid leukemia (AML). In this
      study, we examined the underlying mechanisms in VPA-mediated activities in AML
      cells. VPA not only inhibited the growth of HL-60, U937 and NB4 cells by causing
      cell-cycle arrest at G(0)/G(1) phase and apoptosis, but also induced morphologic
      and phenotypic changes. VPA markedly increased p21WAF1, and downregulated c-Myc
      expression at transcriptional levels. Ectopic expression of wildtype c-Myc and
      T58A mutant significantly inhibited VPA-mediated growth inhibition. As with
      results from cell line studies, VPA also downregulated c-Myc levels, and induced
      apoptosis and myeloid differentiation of primary AML cells, leading to decreased
      colony-forming ability. Given the role of c-Myc in leukemogenesis, our study
      suggests that VPA might be a potential therapeutic agent for AML.

PMID- 17445887
TI  - Cumulative stress and substantiated maltreatment: the importance of caregiver
      vulnerability and adult partner violence.
AB  - OBJECTIVE: Our goal is to assess the effect of caregiver vulnerabilities, singly
      and in combination, on the substantiation of child abuse (physical, sexual) and
      neglect, while controlling for relevant background variables. We test the
      moderator role of adult partner violence in qualifying the relationship between
      caregiver vulnerabilities and maltreatment substantiation. METHOD: Secondary
      analyses of the 1998 Canadian Incidence Study of Reported Child Maltreatment
      (CIS) are used to predict child protective service investigation substantiation
      versus non-substantiation from a range of caregiver vulnerability factors.
      Involvement in partner violence was examined as a moderator in the relation
      between caregiver vulnerabilities and maltreatment substantiation. The CIS is an
      epidemiological survey of first-reported cases to child protective services,
      using a random sample of child welfare agencies across Canada. Child welfare
      workers completed a research form on the child, primary caregiver, family,
      perpetrator, severity and type of maltreatment, as well as services and court
      outcomes. All maltreatment classifications were assigned according to the
      Canadian legal definition of child abuse and neglect. Hierarchical logistic
      regression analyses were used, with stepped entry of: (1) demographic factors,
      socioeconomic disadvantage, and caregiver's own history of maltreatment; (2)
      caregiver vulnerability factors; (3) involvement in partner violence; (4) the
      interaction between caregiver vulnerability and partner violence. RESULTS:
      Caregiver substance abuse was found to be the single most potent kind of
      caregiver vulnerability in predicting maltreatment substantiation. When the total
      number of vulnerabilities was used as the predictor, prediction across all types
      of maltreatment increased, especially for substantiated neglect. Analyses also
      showed that the presence of partner violence in the home exacerbated the effect
      of caregiver vulnerability on substantiation. CONCLUSIONS: The total number of
      caregiver vulnerabilities was the best predictor of the substantiation of child
      abuse and neglect. This relationship was moderated by the existence of partner
      violence: high caregiver vulnerability and high partner violence increased the
      likelihood of substantiation versus non-substantiation. These results suggest
      that caregiver issues should be considered in tandem with partner relationships.
      Among child welfare cases, caregiver vulnerability and partner violence are
      critical targets for child maltreatment prevention and early child protective
      services intervention.

PMID- 17445888
TI  - Toxic effects of albendazole on adenosine triphosphatase activity and
      ultrastructure in Eisenia fetida.
AB  - Veterinary drug may influence soil fauna through manure excretion and subsequent
      application to agricultural field. The aim of this study is to determine the
      toxicity of albendozale (ABZ) on the whole earthworm as well as its different
      regions. Earthworms of Eisenia fetida were exposed to ABZ at 0, 100, 200, 400,
      and 600 mg kg(-1) concentrations; samples were taken at days 2, 7, and 14
      exposure for determination of two adenosine triphosphatase (Na(+)-K(+)- and
      Mg(2+)-ATPase) activities and survival and growth rate. In addition, the
      ultrastructure of intestinal epithelium of the earthworms was examined after 14
      day exposure. The survival and growth rate were reduced as compared to the
      control at the two highest concentrations (400 and 600 mg kg(-1)) after 7- and 14
      day exposure. With increasing ABZ concentration, ATPase activities were inhibited
      significantly in the mid-part after 7 and 14 days and the posterior after 14
      days. In particular, the inhibition effect was significant even at the lower
      treatment levels (100 and 200 mg kg(-1)) after 14 days. Both ATPase activities,
      however, were increased significantly in the anterior of earthworms at the
      highest concentration (600 mg kg(-1)) after 14 days. Ultrastructure observation
      in intestine epithelium in three concentrations (control, 100, 600 mg kg(-1))
      revealed that mitochondria and smooth endoplasmic reticulum were damaged with
      increasing ABZ concentration. Some mitochondria was exhibited the damage of inner
      membrane at 100 mg kg(-1) and vacuolization at 600 mg kg(-1), which is consistent
      with ATPase activities inhibition. The investigation of enzymatic activities in
      different regions of earthworms and pathological alterations in the intestinal
      epithelium can provide important information in terms of toxic effects of soil
      contamination and be used as early warning systems.

PMID- 17445889
TI  - Monitoring metals in terrestrial environments within a bioavailability framework
      and a focus on soil extraction.
AB  - Bioavailability considerations are one of the tools for a proper assignment of
      sites potentially and actually at risk as it allows assessing both the extent
      (hazard) and probability (risk) of adverse effects. In this paper,
      bioavailability considerations are linked to physico-chemical methods available
      for assessing metal fractions in soils. The focus of the overview is on empirical
      methods for extraction of metals from soils as a surrogate for the metal-,
      species- and soil-type-dependent bioavailable and bioaccessible metal pools. This
      cumulates in a generalized flow chart for monitoring of metals in soils. In
      support of the general monitoring strategy, examples are given of successful
      applications of analytical methods for predicting metal uptake by plants and
      animals, for assessing the origin of metals in soils, as well as the leaching
      potential of soils and the extent of soil contamination. It is concluded that a
      large arrays of chemical assessment methodologies for metal speciation in solid
      and liquid soil phases are available. As most assessment methodologies are
      operationally defined instead of being functionally defined, examples of
      mechanistically based monitoring approaches of bioavailability are still scarce.
      The value of the methods for measuring bioavailability can be significantly
      improved when the species, metal, and soil specific aspects of bioavailability
      are more accurately taken into account in the design of chemical simulation
      methodologies.

PMID- 17445890
TI  - Effect of lead pollution on testate amoebae communities living in Sphagnum
      fallax: an experimental study.
AB  - We studied the effects of lead pollution on testate amoebae communities living on
      Sphagnum fallax by growing this moss under controlled conditions. A progressive
      series of lead (Pb) concentration was used in the growing solution of the mosses:
      0 (control), 625 and 2,500 microgL(-1). The mosses were sampled and analysed for
      accumulated Pb and testate amoeba communities after 0, 6, 12, and 20 weeks.
      Species richness, total density and total biomass of testate amoebae declined in
      response to the Pb treatment and changed over time. The Pb x Time cross-effect
      was significant for species richness, and total density but not for the total
      biomass and Shannon diversity. Furthermore, the testate amoebae species richness
      and the total density were negatively correlated to the Pb concentrations
      actually accumulated in the moss at the end of the experiment. Species-specific
      responses of testate amoebae to Pb pollution were identified. Our results thus
      confirm the sensitivity of testate amoebae to lead pollution.

PMID- 17445892
TI  - The use of pigs in neuroscience: modeling brain disorders.
AB  - The use of pigs in neuroscience research has increased in the past decade, which
      has seen broader recognition of the potential of pigs as an animal for
      experimental modeling of human brain disorders. The volume of available
      background data concerning pig brain anatomy and neurochemistry has increased
      considerably in recent years. The pig brain, which is gyrencephalic, resembles
      the human brain more in anatomy, growth and development than do the brains of
      commonly used small laboratory animals. The size of the pig brain permits the
      identification of cortical and subcortical structures by imaging techniques.
      Furthermore, the pig is an increasingly popular laboratory animal for transgenic
      manipulations of neural genes. The present paper focuses on evaluating the
      potential for modeling symptoms, phenomena or constructs of human brain diseases
      in pigs, the neuropsychiatric disorders in particular. Important practical and
      ethical aspects of the use of pigs as an experimental animal as pertaining to
      relevant in vivo experimental brain techniques are reviewed. Finally, current
      knowledge of aspects of behavioral processes including learning and memory are
      reviewed so as to complete the summary of the status of pigs as a species
      suitable for experimental models of diverse human brain disorders.

PMID- 17445893
TI  - Spontaneous attentional fluctuations in impaired states and pathological
      conditions: a neurobiological hypothesis.
AB  - In traditional accounts, fluctuations in sustained and focused attention and
      associated attentional lapses during task performance are regarded as the result
      of failures of top-down and effortful higher order processes. The current paper
      reviews an alternative hypothesis: that spontaneous patterns of very low
      frequency (<0.1 Hz) coherence within a specific brain network ('default-mode
      network') thought to support a pattern of generalized task-non-specific cognition
      during rest, can persist or intrude into periods of active task-specific
      processing, producing periodic fluctuations in attention that compete with goal
      directed activity. We review recent studies supporting the existence of the
      resting state default network, examine the mechanism underpinning it, describe
      the consequent temporally distinctive effects on cognition and behaviour of
      default-mode interference into active processing periods, and suggest some
      factors that might predispose to it. Finally, we explore the putative role of
      default-mode interference as a cause of performance variability in attention
      deficit/hyperactivity disorder.

PMID- 17445894
TI  - Non-accidental brain trauma in infants: diffusion imaging, contributions to
      understanding the injury process.
AB  - Analysis of MRI diffusion images from 33 infants suffering from non-accidental
      trauma reveals five patterns of injury. These are diffuse supratentorial hypoxic
      ischemic, watershed hypoxic ischemic, venous infarction, diffuse axonal injury
      and contusion.

PMID- 17445895
TI  - Prevertebral abscess mimicking a retropharyngeal abscess and revealing a double
      location spondylodiscitis: case report.

PMID- 17445896
TI  - Responding to violence against women: social science contributions to legal
      solutions.
AB  - Violence against women represents a serious problem in America. Not only does
      intimate partner violence represent a significant threat to women, but it also
      counts among its victims, children living in the violent household. By its very
      nature, intimate partner or domestic violence may be approached as either a legal
      or a social problem. However, there is a shortage of legal approaches that have
      been informed by sound social science research. One promising framework for
      developing such integrated responses to intimate partner violence is therapeutic
      jurisprudence, which encourages legal professionals to work closely with social
      scientists to develop system responses based on empirical data. Such an approach
      contrasts sharply with the current practice of developing law based on
      assumptions, which frequently reflect traditional paternalistic and sexist
      attitudes toward women. This paper begins by examining the current theories and
      scientific knowledge on domestic violence with particular emphasis on the
      supporting data. A theoretical framework for conceptualizing domestic violence
      characterized as patriarchal terrorism as distinct from common couple violence is
      examined and offered as a means of explaining inconsistencies in research
      findings. Following a review of current legal responses to domestic violence, the
      paper concludes by outlining alternative strategies and recommendations for
      future efforts that are supported by current theory and research.

PMID- 17445897
TI  - Spherical aberration and depth of focus in eyes implanted with aspheric and
      spherical intraocular lenses: a prospective randomized study.
AB  - PURPOSE: To compare distance-corrected, near, and intermediate visual acuities as
      a measurement of depth of focus and spherical aberration of eyes implanted with
      aspheric and spherical intraocular lenses (IOLs). DESIGN: Randomized prospective
      study. PARTICIPANTS: One hundred twenty eyes of 60 patients with bilateral
      cataract implanted with 3 IOL models (AcrySof IQ, AcrySof SN60AT [Alcon
      Laboratories, Fort Worth, TX], and Sensar AR40 [Allergan Surgical, Irvine, CA]).
      METHODS: Pupil diameter was analyzed by using a Colvard pupillometer (OASIS
      Medical, Inc., Glendora, CA) under photopic, mesopic, and scotopic conditions.
      Distance (6 m), intermediate (1 m), and near (0.33 m) visual acuities were
      measured with distance correction in place 90 days after surgery. Wavefront
      analysis (LadarWave; Alcon Laboratories) was performed using 5-mm and measured
      photopic pupil diameter at 30 and 90 days after surgery. MAIN OUTCOME MEASURES:
      To evaluate spherical aberration and depth of focus (by means of distance
      corrected near and intermediate visual acuity) in patients implanted with
      aspheric and spherical IOLs. RESULTS: Photopic pupil sizes in each group were
      similar at 30 days after surgery. At 90 days after surgery, mean logarithm of the
      minimum angle of resolution distance-corrected near visual acuity (+/-standard
      deviation [SD]) was 0.50+/-0.20 in the AcrySof IQ group, 0.38+/-0.17 in the
      AcrySof SN60AT group, and 0.45+/-0.16 in Sensar AR40 group. Mean spherical
      aberration values (+/-SD) were 0.03+/-0.05 microm in the AcrySof IQ group, 0.24+/
      0.04 microm in the AcrySof SN60AT group, and 0.14+/-0.07 microm in the Sensar
      AR40 group. The AcrySof IQ group showed a statistically significant lower
      induction of spherical aberration and worse distance-corrected near visual
      acuity. The AcrySof SN60AT group showed statistically significant higher mean
      spherical aberration values and better distance-corrected near and intermediate
      visual acuity. CONCLUSIONS: The reduction of total spherical aberration after
      aspheric IOL implantation may degrade distance-corrected near and intermediate
      visual acuity.

PMID- 17445898
TI  - Preoperative sub-Tenon's capsule injection of ropivacaine in conjunction with
      general anesthesia in retinal detachment surgery.
AB  - OBJECTIVE: To evaluate the effects of preoperative sub-Tenon's capsule injection
      of ropivacaine on intraoperative hemodynamics, postoperative pain, nausea, and
      recovery in patients undergoing scleral buckling surgery under general anesthesia
      (GA). DESIGN: Randomized double-masked controlled clinical trial. PARTICIPANTS:
      Ninety-eight patients with primary rhegmatogenous retinal detachment undergoing
      scleral buckling surgery under GA. METHODS: Random allocation to either
      preoperative sub-Tenon's capsule injection of 3 ml of 0.75% ropivacaine or sub
      Tenon's capsule injection of 3 ml of saline (controls) immediately before a
      scleral buckling procedure under GA. Intraoperative monitoring of hemodynamic
      parameters, need of analgesia with sevoflurane and alfentanil, time in the
      recovery unit, measurements of pain and nausea on the visual analog scale (VAS)
      up to 12 hours postoperatively, and consumption of analgesics and antiemetics was
      recorded. MAIN OUTCOME MEASURES: Intraoperative systolic blood pressure (BP);
      bradycardia; minimum alveolar concentration (MAC) of sevoflurane; maximum
      postoperative VAS scores of pain and nausea; time in recovery unit; and total
      need of alfentanil, ketobemidone, dextropropoxyphene, and dixyrazine. RESULTS:
      Ninety-seven patients were analyzed (48 in the ropivacaine group and 49
      controls). A significantly lower intraoperative systolic BP (104+/-6 vs. 112+/-7
      mmHg; P = 0.004), less need of sevoflurane (1.33+/-0.19 vs. 1.56+/-0.23; P =
      0.03), and shorter time in the recovery unit (67+/-9 vs. 76+/-16 minutes; P =
      0.01) were observed in the ropivacaine group. Maximum VAS pain scores were 50+/
      21 in the control group and 36+/-25 in the ropivacaine group (P = 0.05), with a
      significantly lower consumption of opioids (ketobemidone) in the ropivacaine
      group (3.6+/-3.5 vs. 1.3+/-2.0 mg). No significant difference was observed
      regarding nausea or need of dixyrazine or dextropropoxyphene postoperatively.
      CONCLUSIONS: Preoperative sub-Tenon's capsule injection of ropivacaine in scleral
      buckling surgery under GA lowers the intraoperative systolic BP, reduces the
      amount of inhalable sevoflurane needed, and enhances postoperative vigilance
      through reduction of pain and need of opioids.

PMID- 17445899
TI  - Diagnostic ability of Heidelberg Retina Tomograph 3 classifications: glaucoma
      probability score versus Moorfields regression analysis.
AB  - PURPOSE: To evaluate the usefulness of the glaucoma probability score (GPS),
      which does not require manual outlining of the disc boundaries, and the
      Moorfields regression classification (MRA), which requires manual outlining of
      the disc boundaries, for discriminating between healthy and glaucomatous eyes,
      using the Heidelberg Retina Tomograph. DESIGN: Cross-sectional study.
      PARTICIPANTS: We prospectively selected 71 consecutive healthy subjects and 115
      consecutive patients with open-angle glaucoma. METHODS: Participants were divided
      into 2 groups depending on the results of standard automated perimetry and
      intraocular pressure. All participants underwent imaging of the optic nerve head
      with the Heidelberg Retina Tomograph 3. All tests were performed within 1 month
      of each subject's date of enrollment into the study by examiners masked to the
      other findings. MAIN OUTCOME MEASURES: The sensitivity and specificity of all
      parameters of the MRA and GPS classifications were calculated. The diagnostic
      accuracy at different severities of glaucoma and optic disc sizes was also
      evaluated. Receiver operating characteristic curves were plotted for the GPS
      values. RESULTS: The MRA global classification had a sensitivity of 73.9% and a
      specificity of 91.5%. The GPS global classification had a sensitivity of 58.2%
      and a specificity of 94.4%. The GPS had slightly higher sensitivity and somewhat
      lower specificity than the MRA when there was mild damage indicated by visual
      field tests. The MRA had the best discrimination capability for moderate and
      severe glaucoma. Both the GPS and MRA had lower sensitivity and higher
      specificity for small optic discs (<1.7 mm2) compared with medium and large
      discs. CONCLUSIONS: In general, the diagnostic performance of the GPS was similar
      to that of the MRA. The diagnostic accuracy of both classifications depends on
      the optic disc size and the glaucoma severity.

PMID- 17445900
TI  - Relationship of macular microcirculation and retinal thickness with visual acuity
      in diabetic macular edema.
AB  - PURPOSE: To assess perifoveal capillary blood flow velocity (BFV), capillary
      occlusion, and retinal thickness at the central fovea in diabetic patients with
      or without clinically significant macular edema; to examine the relationships of
      these variables with visual acuity (VA); and to identify their contributions to
      visual outcome and diabetic macular edema. DESIGN: Comparative cross-sectional
      prospective study. PARTICIPANTS AND CONTROLS: Diabetic patients with clinically
      significant macular edema (CSME) (n = 22), matched diabetic patients without CSME
      (n = 22), and healthy volunteers (n = 16). METHODS: Capillary BFV was measured by
      fluorescein angiography using a scanning laser ophthalmoscope and was analyzed by
      the tracing method. Severity of perifoveal capillary abnormalities was classified
      by the size and outline of the foveal avascular zone (FAZ) and extent of foveal
      capillary loss. Macular thickness was measured by optical coherence tomography.
      Each subject underwent a complete ophthalmic evaluation, and best-corrected VA
      (BCVA) was converted to the logarithm of the minimum angle of resolution scale.
      MAIN OUTCOME MEASURES: Relationship of perifoveal capillary BFV, capillary
      occlusion, and foveal thickness with VA. RESULTS: Best-corrected VA significantly
      differed among all 3 groups (P<0.0001). Best-corrected VA correlated negatively
      with BFV (r = -0.644, P<0.0001) among all subjects and positively with retinal
      thickness at the central fovea in diabetic patients with CSME (r = 0.640, P =
      0.0013). There was a positive correlation between BCVA and severity in the size
      of the FAZ (r = 0.484, P = 0.0015), outline of the FAZ (r = 0.542, P = 0.0004),
      and extent of foveal capillary loss (r = 0.585, P = 0.0001) among all diabetic
      subjects. Multiple regression analysis showed that retinal thickness at the
      central fovea was the only variable that significantly predicted VA (standardized
      regression coefficient, 0.635; P = 0.0001). CONCLUSIONS: Best-corrected VA was
      associated with perifoveal capillary BFV, severity of perifoveal capillary
      occlusion, and retinal thickness at the central fovea in diabetic patients, but
      the greatest contributing factor was only the retinal thickness.

PMID- 17445901
TI  - Evaluation of deep lamellar endothelial keratoplasty surgery using scatterometry
      and wavefront analyses.
AB  - OBJECTIVE: To determine if postsurgical corneal interface abnormalities after
      deep lamellar endothelial keratoplasty (DLEK) cause increased light scattering or
      wavefront aberrations that may help to explain decreased best-corrected visual
      acuity in DLEK patients compared with penetrating keratoplasty (PK) patients.
      DESIGN: Prospective comparative case series. PARTICIPANTS: Clinically clear
      corneas of 4 eyes that had undergone DLEK surgery and 4 eyes that had PK were
      studied. Normal control data for light scattering was collected from 12 right
      eyes and 11 left eyes with normal corneas. METHODS: Corneal light scattering was
      measured with a scatterometer designed at the Johns Hopkins Applied Physics
      Laboratory, and wavefront analysis was performed using standard methods with a
      Hartmann-Shack wavefront sensor. MAIN OUTCOME MEASURES: Corneal scattering
      measurements were normalized by taking the ratio of the subject's corneal light
      scattering to a reference material. A scattering index was calculated as the
      ratio of the normalized scattering for a given patient's cornea to the average
      scattering of normal corneas. Astigmatism and higher-order aberrations were
      analyzed using standard data output from wavefront analysis and Zernike
      polynomial decomposition. RESULTS: The mean scattering index was significantly
      higher after DLEK (1.78+/-0.29, mean+/-standard deviation [SD]) than after PK
      (1.03+/-0.27; P = 0.043). The higher-order root mean square (RMS) wavefront error
      was significantly higher after PK (0.71+/-0.11 microm, mean+/-SD) than after DLEK
      (0.44+/-0.12 microm; P = 0.029). Zernike polynomial decomposition of the
      wavefront aberrations revealed that regular corneal astigmatism was the most
      important aberration component for both PK and DLEK, but the PK patients had
      significantly more regular astigmatism (1.7+/-0.45 diopters [D], mean+/-SD) than
      did the DLEK patients (0.84+/-0.27 D; P = 0.029). CONCLUSIONS: Our data
      quantitatively support subclinical corneal haze as an explanation for the limited
      visual acuity after DLEK as compared with PK. Intraoperative or postoperative
      modifications to reduce stromal haze after DLEK may result in better visual
      acuity outcomes.

PMID- 17445902
TI  - Bromfenac ophthalmic solution 0.09% (Xibrom) for postoperative ocular pain and
      inflammation.
AB  - OBJECTIVE: To evaluate the efficacy and ocular safety of bromfenac ophthalmic
      solution 0.09% (Xibrom) for the treatment of postoperative inflammation and
      reduction of ocular pain in subjects who have undergone cataract extraction (CE).
      DESIGN: Two phase III, multicenter, randomized, double-masked, parallel, placebo
      controlled clinical trials were conducted under a common protocol. Data were
      pooled for analyses. PARTICIPANTS: Five hundred twenty-seven subjects were
      sequentially assigned, according to a computer-generated randomization list
      (2:1), to bromfenac (n = 356) or a placebo (n = 171). INTERVENTION: Subjects who
      underwent cataract surgery without prior antiinflammatory treatment with a
      postsurgical Summed Ocular Inflammation Score (SOIS) of > or =3 were treated with
      either bromfenac or the placebo, instilled twice daily for 14 days in the study
      eye, and observed for an additional 14 days for safety evaluation. MAIN OUTCOME
      MEASURE: Cleared ocular inflammation with a SOIS of 0 (cells< or =5 and absence
      of flare after 14 days of treatment). Secondary outcomes included time to
      resolution of ocular inflammation, time to resolution of ocular pain, proportion
      of subjects with photophobia, and ocular adverse events. RESULTS: Baseline
      characteristics were comparable between groups for age, gender, and race. The
      baseline mean SOIS was 3.7 in both groups. A greater proportion of bromfenac
      (64.0%) than placebo subjects (43.3%) achieved complete clearance of ocular
      inflammation at study day 15 (P<0.0001). The effect of bromfenac on clearance of
      ocular inflammation was as early as study day 3 after initiation of treatment,
      compared with the placebo (8.4% vs. 1.2%, P = 0.0012). The median time to
      resolution of ocular pain was 2 days (bromfenac) versus 5 days (placebo)
      (P<0.0001). Numbers of most ocular adverse events were lower for the bromfenac
      group than for the placebo group. Eye irritation was reported in a lower
      percentage of subjects for bromfenac (2.5%) versus placebo (4.7%), as were
      burning and stinging (1.4% vs. 2.5%), and photophobia (2.0% vs. 11.1%).
      CONCLUSIONS: Bromfenac ophthalmic solution 0.09% effectively and rapidly cleared
      ocular inflammation and reduced ocular pain after CE. There were no serious
      ocular adverse events, and fewer adverse events were reported for the bromfenac
      group.

PMID- 17445903
TI  - Electrochemical behavior of neomycin at DNA-modified gold electrodes.
AB  - Deoxyribonucleic acid (DNA) modified gold electrodes are prepared by the dry
      adsorptive method and the electrochemical behavior of neomycin and the influence
      of Pb(II) are studied by cyclic voltammetry, chronocoulometry, differential pulse
      voltammetry. It is found that in 0.01M phosphate-buffered saline (PBS) buffer
      solutions (pH 7.3) at DNA/Au electrode neomycin exhibits an irreversible cathodic
      peak (E(p)=0.489V), which is more positive and less sensitive compared with that
      at bare gold electrodes (E(p)=0.423V). In the presence of Pb(II) the peak shifts
      toward positive with its height increasing. Moreover, the peak height is linear
      to neomycin concentration over the range of 0.15-57microM. The interaction of
      Pb(II)-neomycin complex with calf thymus DNA is also studied by calculating the
      binding constants (K) of the Pb(II)-neomycin complex to DNA and binding site size
      (s) from voltammetric data (1.0x10(7)M(-1) and 4bp, respectively).

PMID- 17445891
TI  - Neurobiological mechanisms for the regulation of mammalian sleep-wake behavior:
      reinterpretation of historical evidence and inclusion of contemporary cellular
      and molecular evidence.
AB  - At its most basic level, the function of mammalian sleep can be described as a
      restorative process of the brain and body; recently, however, progressive
      research has revealed a host of vital functions to which sleep is essential.
      Although many excellent reviews on sleep behavior have been published, none have
      incorporated contemporary studies examining the molecular mechanisms that govern
      the various stages of sleep. Utilizing a holistic approach, this review is
      focused on the basic mechanisms involved in the transition from wakefulness,
      initiation of sleep and the subsequent generation of slow-wave sleep and rapid
      eye movement (REM) sleep. Additionally, using recent molecular studies and
      experimental evidence that provides a direct link to sleep as a behavior, we have
      developed a new model, the cellular-molecular-network model, explaining the
      mechanisms responsible for regulating REM sleep. By analyzing the fundamental
      neurobiological mechanisms responsible for the generation and maintenance of
      sleep-wake behavior in mammals, we intend to provide a broader understanding of
      our present knowledge in the field of sleep research.

PMID- 17445904
TI  - An efficient P300-based brain-computer interface for disabled subjects.
AB  - A brain-computer interface (BCI) is a communication system that translates brain
      activity into commands for a computer or other devices. In other words, a BCI
      allows users to act on their environment by using only brain-activity, without
      using peripheral nerves and muscles. In this paper, we present a BCI that
      achieves high classification accuracy and high bitrates for both disabled and
      able-bodied subjects. The system is based on the P300 evoked potential and is
      tested with five severely disabled and four able-bodied subjects. For four of the
      disabled subjects classification accuracies of 100% are obtained. The bitrates
      obtained for the disabled subjects range between 10 and 25bits/min. The effect of
      different electrode configurations and machine learning algorithms on
      classification accuracy is tested. Further factors that are possibly important
      for obtaining good classification accuracy in P300-based BCI systems for disabled
      subjects are discussed.

PMID- 17445905
TI  - Optimized protocols for isolation of primary motor neurons, astrocytes and
      microglia from embryonic mouse spinal cord.
AB  - Neuron-glial interactions are important in development of the nervous system and
      pathogenesis of disease. Primary cell cultures prepared from nervous tissue are
      often used to study the properties of individual cell types and how they interact
      with each other. Isolation of pure populations of cells and their culture is
      challenging, particularly from murine spinal cord. The purpose of this study was
      to optimize various protocols to achieve efficient, parallel isolation and
      purification of primary motor neurons, microglia and astrocytes from the same
      mouse embryonic spinal cord sample. Following dissociation of E12 embryonic
      spinal cords, motor neurons were isolated at 97% purity by a single step
      centrifugation of the cell suspension through multiple discontinuous density
      gradients of NycoPrep. The residual mixed cell pellet was resuspended and
      cultured for 2 weeks. Mixed cultures were then shaken to release microglia, which
      were then harvested from the medium and subjected to another round of
      differential adhesion to achieve 99% purity. The astrocytes remaining in the
      mixed cultures were culled to 98% purity by treatment with leucine methyl ester
      and a subsequent vigorous shaking step to remove any remaining microglia and
      neurons. Furthermore, no cross contamination was observed in the glial cultures.
      This technique provides a simple, convenient, and reliable method of obtaining
      highly purified preparations of motor neurons, microglia and astrocytes from
      embryonic spinal cord for the study of spinal cord cell biology and motor neuron
      diseases.

PMID- 17445906
TI  - Anticholinergic use in hospitalised schizophrenic patients in Belgium.
AB  - This naturalistic study aims to evaluate the influence of antipsychotic treatment
      on the use of anticholinergics. The observed use of anticholinergics will give an
      indication of the occurrence of extrapyramidal side effects (EPS) in the
      different antipsychotic treatment conditions. The medication use of 1215
      hospitalised patients with DSM-IV 295.xx diagnosis is recorded. Four
      antipsychotic treatment conditions are distinguished: 1) only first generation
      antipsychotics (FGA): patients receive one or a combination of first generation
      antipsychotics, 2) a combination of high potency FGA and second generation
      antipsychotics (SGA), 3) a combination of low potency FGA and SGA, and 4) only
      SGA: patients receive one or a combination of SGA. Antipsychotic treatment
      significantly influences the use of anticholinergics. Anticholinergic use is
      highest in patients treated with high potency FGA (whether or not in combination
      with SGA) as compared with patients only treated with SGA and patients combining
      SGA with low potency FGA. The two latter groups do not significantly differ.
      However, there were no significant differences in the prevalence of EPS with the
      exception of akathisia between FGA and SGA. Thus, through the use of
      anticholinergics, EPS induced by FGA can be effectively reduced.

PMID- 17445907
TI  - Schizophrenic patients with polydipsia and water intoxication more often have a
      form of schizophrenia first described by Kraepelin.
AB  - Polydipsia and water intoxication (PWI) seem to be associated with a particular
      form of schizophrenia, first described by Kraepelin, involving negative symptoms,
      disorganization and poor outcome. In this study, a group of 20 schizophrenic
      patients with PWI was selected and matched for age, duration of illness and
      gender with a group of 20 schizophrenic controls with no PWI. For these patients
      the following measure were obtained: clinical and demographic data, Keefe's
      criteria for Kraepelinian schizophrenia, the Positive and Negative Syndrome Scale
      score and the score on Fagerstrom's Nicotine Dependence Scale. The group of
      schizophrenic patients with PWI presents significantly higher levels of negative
      symptoms, disorganized symptoms and general symptoms of psychopathology, and it
      is composed of a significantly higher percentage of Kraepelinian patients. These
      results show an association of polydipsia and water intoxication with
      Kraepelinian schizophrenia suggesting physiological hypotheses for a specific
      pathogenic pathway.

PMID- 17445908
TI  - The new GRID Hamilton Rating Scale for Depression demonstrates excellent inter
      rater reliability for inexperienced and experienced raters before and after
      training.
AB  - The Hamilton Rating Scale for Depression (HAMD) is the de facto international
      gold standard for the assessment of depression. There are some criticisms,
      however, especially with regard to its inter-rater reliability, due to the lack
      of standardized questions or explicit scoring procedures. The GRID-HAMD was
      developed to provide standardized explicit scoring conventions and a structured
      interview guide for administration and scoring of the HAMD. We developed the
      Japanese version of the GRID-HAMD and examined its inter-rater reliability among
      experienced and inexperienced clinicians (n=70), how rater characteristics may
      affect it, and how training can improve it in the course of a model training
      program using videotaped interviews. The results showed that the inter-rater
      reliability of the GRID-HAMD total score was excellent to almost perfect and
      those of most individual items were also satisfactory to excellent, both with
      experienced and inexperienced raters, and both before and after the training.
      With its standardized definitions, questions and detailed scoring conventions,
      the GRID-HAMD appears to be the best achievable set of interview guides for the
      HAMD and can provide a solid tool for highly reliable assessment of depression
      severity.

PMID- 17445909
TI  - Low serum albumin and high ferritin levels in chronic hemodialysis patients with
      major depression.
AB  - We investigated the relationships between serum albumin and ferritin levels in
      chronic hemodialysis patients with or without major depression. During a 1-year
      period, a total of 107 chronic hemodialysis patients were recruited. The
      diagnosis of major depression in patients was made by one psychiatrist. The data
      showed that patients with major depression (n=15) had significantly lower albumin
      and higher ferritin levels than patients without major depression (n=92). Chronic
      hemodialysis patients with major depression might have a more severe inflammation
      reaction and greater oxidative damage than patients without major depression.

PMID- 17445910
TI  - Clinical prediction of antidepressant response in mood disorders: linear
      multivariate vs. neural network models.
AB  - Predicting the outcome of antidepressant treatment by pre-treatment features
      would be of great usefulness for clinicians as up to 50% of major depressives may
      not have a satisfactory response in spite of adequate trials of antidepressant
      drugs. In the present article we compared a linear multivariate model of
      predictors with a few artificial neural network (ANN) models differing from one
      another by outcome definition and validation procedure. The sample consisted of a
      reanalysis of 116 inpatients with a major depressive episode included in a 6-week
      open-label trial with fluvoxamine. With the original outcome definition
      (responders/non-responders), ANN performed better than logistic regression (90%
      of correct classifications in the training sample vs. 77%). However only 62% of
      new patients were correctly predicted by ANN for their outcome class. Length of
      the index episode, psychotic features and suicidal behavior emerged as outcome
      predictors in both models, while demographic characteristics, personality
      disorders and concomitant somatic morbidity were pointed to only by ANN analysis.
      Increase of classes in the outcome field resulted in a more elevated error: 46.4%
      for three classes, 60.4% for four classes and 70.3% for five classes. Overall,
      our findings suggest that antidepressant outcome prediction based on clinical
      variables is poor. The ANN approach is as valid as traditional multivariate
      techniques for the analysis of psychopharmacology studies. The complex
      interactions modelled through ANN may eventually be applied at the clinical level
      for individualized therapy. However, the accuracy of prediction is still far from
      satisfactory from a clinical point of view.

PMID- 17445911
TI  - The sensitivity and psychometric properties of a brief computer-based cognitive
      screening battery in a depression clinic.
AB  - At present, there is poor accuracy in assessing cognitive and vegetative symptoms
      in depression using clinician or self-rated measures, suggesting the need for
      development of standardized tasks to assess these functions. The current study
      assessed the psychometric properties and diagnostic specificity of a brief
      neuropsychological screening battery designed to assess core signs of depression;
      psychomotor retardation, attention and executive functioning difficulties, and
      impaired emotion perception within an outpatient psychiatry setting. Three
      hundred eighty-four patients with mood disorders and 77 healthy volunteers
      participated. A large percentage of patients met diagnostic criteria for Major
      Depressive Disorder alone (49%) or with another comorbid psychiatric disorder
      (24%). A brief, 25-min battery of computer-based tests was administered to
      control participants and patients measuring the constructs of inhibitory control,
      attention, visual perception, and both executive and visual processing speed. The
      patient groups performed significantly worse than the control group regardless of
      diagnosis on visual perception and attention accuracy and processing speed
      factors. Surprisingly, the anxiety disorder group performed better than several
      other psychiatric disorder groups in inhibitory control accuracy. Developing
      valid and reliable measures of cognitive signs in mood disorders creates
      excellent opportunities for tracking cognitive status prior to initiation of
      treatment, and allows for reliable retest following treatment.

PMID- 17445912
TI  - Ecchymoses as an adverse effect of fluoxetine treatment.
AB  - We report a case of a 28-year-old major depressive female patient who manifested
      ecchymoses following fluoxetine use. After substitution of sertraline, her
      depression resolved after 4 weeks and ecchymoses 1.5 months latter. This is an
      unexplored side-effect with unknown long-term consequences that warrants further
      study.

PMID- 17445913
TI  - Neuraminidase inhibitor susceptibility of porcine H3N2 influenza A viruses
      isolated in Germany between 1982 and 1999.
AB  - As an intermediate host of avian and human influenza A viruses (FLUAV) pigs may
      play a potential role in interspecies virus transmission and reassortment of
      viral genes including those conferring antiviral drug resistance. Porcine FLUAV
      isolated in Germany between 1989 and 2001 contains mutations in the M2 gene
      inducing amantadine resistance. No data exist on neuraminidase inhibitor (NAI)
      susceptibility of these porcine FLUAV. We studied the antiviral activity of NAI
      against seven selected H3N2 FLUAV isolated from pigs in Germany between 1982 and
      1999. All isolates were susceptible towards oseltamivir and zanamivir in
      neuraminidase enzyme-inhibition assays. Both compounds inhibited virus spreading
      and reduced the virus yields and plaque size at low concentrations. Higher
      concentrations were necessary to reduce the plaque number. Two isolates that
      differed in glycosylation pattern of viral hemagglutinin (HA) showed markedly
      reduced drug susceptibility in cell culture-based assays.

PMID- 17445914
TI  - Single-unit responses to 22 kHz ultrasonic vocalizations in rat perirhinal
      cortex.
AB  - Rats emit ultrasonic vocalizations (USVs) as social signals in several
      situations. Lesion studies have shown that rat perirhinal cortex (PR), a
      polymodal sensory region that is reciprocally connected with the amygdala, is
      critical for normal fear conditioning to so-called "22 kHz USVs". Here we
      evaluated single-unit responses in rat PR to 22 kHz USVs and other acoustic
      stimuli. One question was whether PR circuits are specifically and preferentially
      tuned, prior to fear conditioning, to respond to USVs and USV-like stimuli. Two
      22 kHz USVs were pre-recorded from different conspecifics. Each USV consisted of
      a "bout" of several discrete calls. Using experimentally naive rats, single-unit
      responses to the USVs were compared with responses to continuous or discontinuous
      tones that had the same root frequency as the USVs (19 or 22 kHz). The on/off
      patterns of the discontinuous tones were temporally matched to the call structure
      in the corresponding USVs. Compared to continuous tones, the USVs were no more
      likely to elicit single-unit firing changes in PR. On the other hand, the
      continuous tones and USVs clearly did elicit different firing patterns in many
      units. More specifically, the USVs sometimes elicited a transient increase in
      discharge frequency to each call in a bout of calls. Interestingly, the USVs and
      the temporally matched tone segments usually elicited similar firing patterns.
      The USV-elicited firing pattern in PR thus appears to be controlled by the on/off
      temporal structure of the calls rather than by the frequency or amplitude
      modulations associated with each call in a bout of calls.

PMID- 17445915
TI  - Involvement of the lateral septum and the ventral Hippocampus in the emotional
      sequelae induced by social defeat: role of glucocorticoid receptors.
AB  - An important area of the brain aversive circuitry is the lateral septum (LS),
      together with its principal connections to diverse Hippocampal regions. The aim
      of this work was to evaluate whether the LS-Hippocampus network participates in
      the increased anxiety-like behavior produced by a previous defeat experience. The
      neural activation of different regions of the Hippocampus was assessed by the
      number of Fos positive cells in animals previously defeated. A notable elevation
      in the expression of this protein was observed in CA1, CA2, CA3, and Dentate
      Gyrus, for both dorsal and ventral Hippocampus. The local administration of a
      glucocorticoid receptor (GR or type II) antagonist, but not of a mineralcorticoid
      receptor (MR or type II) antagonist, into the LS before the stressful stimuli
      prevented a rise in the number of Fos positive cells, especially in the ventral
      portion of the Hippocampus. Furthermore, to evaluate the role of these
      hippocampal portions in the modulation of the emotional sequelae induced by
      defeat, the dorsal or the ventral Hippocampus were inactivated by lidocaine at
      different times following the social confrontation, with the anxiety-like
      behavior being assessed in the elevated plus maze the next day. Only the
      inactivation of the ventral region attenuated the excessive anxiety exhibited by
      defeated animals. The infusion of lidocaine, 1h after the confrontation, did not
      affect this behavioral response. These data suggest a preferential participation
      of the LS and its connections to the ventral Hippocampus in the emotional
      sequelae induced by the social defeat. Moreover, the GR localized within the LS
      played an essential role in the modulation of this emotional state.

PMID- 17445916
TI  - Mood and male sexual behaviour in the APP23 model of Alzheimer's disease.
AB  - Alzheimer's disease is characterised by both cognitive deterioration and the
      development of a wide range of neuropsychiatric disturbances, among which
      affective disturbances, stereotyped behaviour, dietary hyperactivity and changes
      in sexual behaviour. The transgenic APP23 mouse models Alzheimer's disease and
      has shown to be a unique tool in the study of this condition. APP23 mice develop,
      next to the age-dependent cognitive decline, also a range of behavioural
      problems, such as circadian activity disturbances and increased aggression, in
      analogy with the dementing patients. The present study aimed to investigate
      whether this model also develops mood disturbances and changes in sexual
      behaviour. Using two behavioural despair paradigms and the sucrose preference
      test, we did not find evidence for the development of depression-related
      behaviours. A sophisticated protocol was neither able to unravel changes in male
      sexual behaviour between APP23 and WT mice. The present study nevertheless
      provides evidence that the APP23 mice are more anxious and fearful in comparison
      with control littermates, which opens perspectives to future treatment studies.

PMID- 17445917
TI  - Effects of 17alpha-ethynylestradiol on EROD activity, spiggin and vitellogenin in
      three-spined stickleback (Gasterosteus aculeatus).
AB  - The three-spined stickleback (Gasterosteus aculeatus) has quantifiable biomarkers
      of exposure to estrogens (vitellogenin), androgens (spiggin) and aryl hydrocarbon
      receptor (AhR) agonists (EROD activity) and is therefore a promising test species
      for biomonitoring of reprotoxic chemicals in aquatic environments. In this study
      we evaluated the effects of 17alpha-ethynylestradiol (EE(2)) on EROD activity,
      induction of vitellogenin and spiggin, hepatosomatic index (HSI), ovarian somatic
      index (OSI) and nephrosomatic index (NSI). Adult male and female three-spined
      sticklebacks were exposed to concentrations of 0-170 ng EE(2)/l (measured
      concentrations) in a flow-through system for 21 days. Exposure to 170 ng EE(2)/l
      resulted in a significant 8- and 9-fold induction of gill EROD activity in males
      and females, respectively. In livers, EROD activity expressed in relation to
      microsomal protein content was suppressed due to a significant increase in
      microsomal protein content. Hepatic EROD activity per se expressed as picomol/min
      was not affected by exposure to EE(2). The lowest observed effect concentration
      for induction of vitellogenin in males was 53.7 ng EE(2)/l. In females,
      vitellogenin levels were significantly higher in those exposed to 170 ng EE(2)/l
      compared to controls. Spiggin production was significantly inhibited and NSI
      lower in males exposed to 170 ng EE(2)/l. In both females and males LSI was
      significantly higher in fish exposed to 170 ng EE(2)/l than in controls. In
      females exposed to 170 ng EE(2)/l, OSI was significantly lower and NSI higher
      than controls. The observed results from this study show that a synthetic
      estrogen can affect the well-known biomarker of exposure for dioxin-like
      compounds, EROD activity, and further that this response can differ between
      tissues. These findings are important for interpretation of biomonitoring data.

PMID- 17445918
TI  - Prevention of inappropriate therapy in implantable defibrillators: A meta
      analysis of clinical trials comparing single-chamber and dual-chamber arrhythmia
      discrimination algorithms.
AB  - INTRODUCTION: A proposed benefit of dual-chamber arrhythmia discrimination is a
      reduction in inappropriate therapy in implantable cardioverter-defibrillators
      (ICDs). The aim of this meta-analysis was to establish whether dual-chamber
      arrhythmia discrimination algorithms reduce inappropriate device therapy. METHODS
      AND RESULTS: Public domain databases, MEDLINE, EMBASE, and Cochrane Register of
      Controlled Trials, were searched from 1996 to 2006. Two investigators abstracted
      data independently. Pooled estimates were calculated using both fixed-effects and
      random-effects models. We retrieved 5 prospective studies comparing dual-chamber
      with single-chamber arrhythmia discrimination, accumulating data on 748 patients.
      Pooled per-patient based analysis demonstrated that the number of patients
      receiving inappropriate ICD therapy was not different between single- and dual
      chamber devices (odds ratio [OR] 1.23; 95% CI, 0.83 to 1.81; p=0.31). Per-episode
      based analysis demonstrated a favoring benefit for dual-chamber arrhythmia
      discrimination (OR 0.64; 95% CI, 0.52 to 0.78; p<0.001). A mean reduction of 1.1
      inappropriately treated atrial episodes per patient was observed with dual
      chamber arrhythmia discrimination (p<0.001). CONCLUSIONS: Dual-chamber arrhythmia
      discrimination is associated with a reduction in the number of inappropriate
      treated episodes. The number of patients who experience inappropriate therapy is
      not reduced by dual-chamber discrimination.

PMID- 17445919
TI  - A paradoxical effect of lidocaine for the N406S mutation of SCN5A associated with
      Brugada syndrome.
AB  - BACKGROUND: Accelerated intermediate inactivation, which is caused by mutations
      in the cardiac voltage-gated sodium channel alpha-subunit gene (SCN5A), is one of
      the molecular mechanisms underlying Brugada syndrome. The N406S mutation
      associated with Brugada syndrome results in the accelerated intermediate
      inactivation, in addition to unique pharmacological characteristics. METHODS:
      Functional sodium channels were expressed transiently in HEK293 cells by
      transfecting equally the alpha- and beta-subunit plasmids (1 microg/ml) and the
      sodium current were measured in whole-cell mode of patch-clamp recording.
      RESULTS: Since the N406S mutant channel has a greatly reduced use-dependent block
      of lidocaine, we took the advantage of the mutant channel to examine the effect
      of lidocaine on intermediate inactivation using wild-type (WT) and N406S mutant
      channels recombinantly expressed in HEK293 cells. Lidocaine (100 microM) slowed
      the recovery from the fast inactivation similarly for WT and N406S. On the other
      hand, whereas lidocaine slowed the recovery from the intermediate inactivation
      for WT, lidocaine accelerated the recovery for N406S. Activity-dependent loss of
      channel availability by repetitive 500-ms pulses was more strongly enhanced and
      accelerated by lidocaine for WT, but lidocaine exerted little effect on the N406S
      channel. CONCLUSION: We demonstrate that lidocaine may suppress Brugada syndrome
      associated with the N406S mutation by preventing the sodium channel from
      accumulating in the intermediate inactivation state.

PMID- 17445920
TI  - Familial conduction system disease associated with hypertrophic cardiomyopathy.
AB  - A large family with a new phenotype of conduction system disease including heart
      blocks and preexcitation associated with hypertrophic cardiomyopathy and
      transmitted in an autosomal dominant pattern is described.

PMID- 17445921
TI  - Contemporary use of adjunctive corticosteroids in tuberculous pericarditis.
AB  - There is controversy concerning the effectiveness of adjunctive corticosteroids
      in reducing mortality in tuberculous pericarditis. To assess the impact of this
      controversy on contemporary clinical practice, we studied the use of adjunctive
      corticosteroid in 185 consecutive patients with suspected pericardial
      tuberculosis from 15 hospitals in Cameroon, Nigeria, and South Africa. 109
      (58.9%) patients received steroids with significant variation in corticosteroid
      use ranging from 0% to 93.5% per centre (P<0.0001). The presence of clinical
      features of HIV infection was the independent predictor of the non-use of
      adjunctive corticosteroids (OR 0.39, 95% CI 0.20-0.75, P=0.005). We have
      demonstrated marked variation in the use of corticosteroids by practitioners,
      with nearly half of all patients not receiving this intervention. Taken together
      with the statistical uncertainty regarding the effectiveness of adjunctive
      steroids in tuberculous pericarditis, these observations probably reflect a state
      of genuine uncertainty or clinical equipoise among practitioners who care for
      patients with tuberculous pericarditis in sub-Saharan Africa. These data provide
      a justification for the establishment of adequately powered randomised clinical
      trials to assess the effectiveness of adjunctive corticosteroids in patients with
      tuberculous pericarditis.

PMID- 17445922
TI  - An unusual complication of pneumococcal pneumonia: acute tamponade due to
      purulent pericarditis.
AB  - The incidence of purulent pericarditis has declined, however mortality remains
      high. Few cases so far of cardiac tamponade related with purulent pericarditis
      which is a rare complication of pneumococcal pneumonia have been published in the
      literature. We report a case of the development of cardiac tamponade due to
      pneumococcal pneumonia and emphasize the importance of early recognition, prompt
      institution of appropriate antibiotic therapy, and early surgical drainage for
      survival.

PMID- 17445923
TI  - Myocardial scintigraphy in a patient with transient mid-ventricular ballooning
      cardiomyopathy: case report.
AB  - We report a case of a 51-year-old man with transient mid-ventricular ballooning
      cardiomyopathy. Left ventriculography demonstrated mid-ventricular ballooning and
      akinesis with hypercontractile apical and basal segments. Iodine-123-beta-methyl
      p-iodophenyl-penta-decanoic acid myocardial scintigraphy showed decreased uptake
      in the mid-ventricle, corresponding to the mid-ventricular akinetic region. This
      is the first report of a transient mid-ventricular ballooning cardiomyopathy
      observed by not only left ventriculography but myocardial scintigraphy.

PMID- 17445924
TI  - Right ventricular outflow tract pacing: relation of high to low synchronous
      ventricular activation with cardiac memory.
AB  - Cardiac memory is usually observed after right ventricular apical pacing and
      considered to be related to alter asynchronous activation by apical pacing.
      However, it is not known whether it occurs by unaltered high to low synchronous
      ventricular activation by right ventricular outflow tract (RVOT) pacing. We
      present here a case with dual chamber pacemaker whose ventricular lead positioned
      in the RVOT and developed cardiac memory immediately after ventricular pacing had
      stopped and the underlying sinus rhythm resumed.

PMID- 17445925
TI  - Is abnormality of double right coronary artery seen more frequently in Turkey
      than the others?

PMID- 17445926
TI  - A retrograde approach for the treatment of chronic total occlusion in a patient
      with acute coronary syndrome.
AB  - Recent instrumental and technical developments have improved the outcomes of
      percutaneous coronary intervention (PCI) for chronic total occlusion (CTO)
      lesions. Recently, several cases of PCI in patients with stable coronary artery
      disease (CAD) using a retrograde approach through the collateral vessels of the
      CTO have been reported. We herein describe firstly a successful PCI for a CTO
      lesion using a retrograde approach in the clinical setting of acute coronary
      syndrome (ACS).

PMID- 17445927
TI  - Concurrent chemoradiation with daily low dose cisplatin for advanced stage head
      and neck carcinoma.
AB  - BACKGROUND AND PURPOSE: To evaluate treatment results of concurrent
      chemoradiation with daily low dose cisplatin. MATERIALS AND METHODS: 121 patients
      with advanced stage HNSCC were treated with RT (35 x 2 Gy) and cisplatin (6
      mg/m(2) i.v. x20, daily before RT). After 47 patients, the treatment protocol
      (Standard Group) was changed: Daily i.v. prehydration and accelerated RT were
      given to the subsequent 74 patients (Hydr-Ac-RT Group). RESULTS: Mean follow-up
      was 29 months (range 7-62). More chemotherapy could be administered in the Hydr
      Ac-RT Group (maximum no. of 20 cisplatin-infusions increased from 59% to 91% of
      patients, p=0.008), with less renal toxicity (p<0.001) and less hospital
      admissions (p<0.02). However, mucositis was more pronounced and tubefeeding more
      frequent in the Hydr-Ac-RT Group. The CR rate of the primary tumor increased from
      74% (Standard Group) to 90% (Hydr-Ac-RT Group) (p=0.06), although this did not
      lead to an improvement in loco-regional control. CONCLUSIONS: Concurrent
      chemoradiation with daily low dose cisplatin is feasible and effective for
      selected patients with advanced HNSCC. Although the addition of accelerated RT
      resulted in more mucositis and tubefeeding, the introduction of prehydration led
      to better compliance to therapy with more chemotherapy administered and less
      hospital admissions.

PMID- 17445928
TI  - A randomised trial of radiotherapy compared with cisplatin chemo-radiotherapy in
      patients with unresectable squamous cell cancer of the esophagus.
AB  - BACKGROUND AND PURPOSE: Following our phase II experience, a randomised trial was
      undertaken to evaluate the efficacy of adding chemotherapy to radiotherapy in
      patients with unresectable squamous cell cancer of the esophagus. PATIENTS AND
      METHODS: Patients randomised to the RT group received 50 Gy/25 fx/5 weeks of
      teletherapy followed 1-2 weeks later with 12 Gy/2 fx of high-dose-rate intra
      lumenal brachytherapy spaced a week apart. Following the first 3 years of
      recruitment, due to unexpected late morbidity, brachytherapy was excluded and the
      protocol modified to 66 Gy/33 fx/6.5 weeks. The CRT group received identical
      radiotherapy with concurrent weekly cisplatin at 35 mg/m(2) for 6-7 cycles.
      RESULTS: Between April 1999 and December 2005, 125 patients were randomised to a
      RT (n=60) or CRT group (n=65). Radiotherapy treatment was completed in 78%
      (47/60) of the RT group and 89% (58/65) of the CRT group (P=0.10). Six or more
      cycles of cisplatin could be delivered in 63% (41/65), which resulted in RTOG
      grade 3 neutropenia of 3%. Late morbidity in the form of ulcers (5% vs. 15% odds
      ratio 0.29, 95% CI 0.08-1.11, P=0.08) and strictures (13% vs. 28%, odds ratio
      0.40, 95% CI 0.16-1.01, P=0.05) was observed in the RT and CRT groups,
      respectively. At a median follow up of 23 months of all patients alive (range 6
      82 months) and with 95/125 events, the median, 1, 2 and 5 year projected survival
      was 7.1 months, 32.3%, 22.8% and 13.7% vs. 13.4 months, 57.6%, 38.9% and 24.8%
      for the RT and CRT groups, respectively (hazard ratio 0.65, 95% CI 0.44-0.98,
      P=0.038). CONCLUSIONS: The addition of concurrent cisplatin to radiotherapy
      resulted in a modest improvement in survival and was associated with manageable
      additional acute and late morbidity.

PMID- 17445929
TI  - Modelling of the growth-no growth interface of Issatchenkia occidentalis, an
      olive spoiling yeast, as a function of the culture media, NaCl, citric and sorbic
      acid concentrations: study of its inactivation in the no growth region.
AB  - A global logistic model incorporating a dummy variable for the growth medium
      (laboratory media or table olives brine) was used for the estimation of the
      growth-no growth interface of Issatchenkia occidentalis as a function of NaCl,
      citric and sorbic acid concentrations. The model permitted the deduction of the
      region where the combination of citric and sorbic acids in laboratory media
      (above 0.3% and 0.03% wt/vol, respectively) and brine (above 0.1% and 0.03%
      wt/vol), at 5% NaCl, inhibited the growth of the yeast. Subsequently, the model
      was validated in laboratory media within the no growth region by a response
      surface D-optimal design. Inactivation concentrations of sorbic acid produced a
      progressive loss of viability in I. occidentalis that followed a first order
      kinetic or downward concave inactivation curves, depending on environmental
      variables. These curves were properly described by a (primary) model deduced from
      the Weibull distribution, whose parameters, first decimal reduction time
      (D(beta)) and shape (beta), were expressed as a function of sorbic acid
      concentrations (secondary model). At 5% NaCl and within the experimental region
      checked, an increase of 0.010% and 0.008% sorbic acid reduced D(beta) in 10 h and
      decrease beta by 10%. Finally, the model was also validated in real "seasoned"
      table olives packing reporting a complete inactivation of the yeasts' population.

PMID- 17445930
TI  - Targeted molecular engineering of a family 11 endoxylanase to decrease its
      sensitivity towards Triticum aestivum endoxylanase inhibitor types.
AB  - The Bacillus subtilis endoxylanase XynA (BSXY) is frequently used to improve the
      functionality of arabinoxylan-containing material in cereal based industries. The
      presence of endogenous Triticum aestivum xylanase inhibitors (TAXI-I and TAXI-II)
      in wheat is a real concern as they have a direct negative impact on the
      efficiency of this enzyme. Here, we used the recently determined structure of the
      complex between TAXI-I and an endoxylanase of Aspergillus niger to develop
      inhibitor-insensitive BSXY variants by site-directed mutagenesis of strategically
      chosen amino acids. We either induced steric hindrance to reject the inhibitors
      or interrupted key interactions with the inhibitors in the endoxylanase substrate
      binding groove. The first strategy was successfully applied to position G12 where
      G12W combined inhibition insensitivity with unharmed catalytic performance.
      Variants from the second strategy showed altered inhibitor sensitivities
      concomitant with changes in enzyme activities and allowed to gain insight in the
      binding-mode of both TAXI-I and TAXI-II with BSXY.

PMID- 17445931
TI  - Exercise training for patients with cardiovascular disease.
AB  - This review surveys effort training, a validated and recommended therapy, in
      patients with atheromatous cardiovascular disease. This true therapy reduces
      mortality by 25-35%, reduces clinical manifestations and complications (rhythm
      problems, thrombosis) and improves physical capacity, reintegration and quality
      of life. The effects are essentially linked to improved metabolic performance of
      muscles and reduced endothelial dysfunction, insulin resistance and neurohormonal
      abnormalities. Training also has an impact on the evolution of major risk
      factors, especially diabetes and arterial hypertension. The risks are limited as
      long as the contraindications are respected and the programmes supervised. The
      indications (stable angina, chronic heart failure, peripheral arterial disease)
      should be described more precisely by taking into account functional criteria:
      physical deconditioning, exclusion, compliance, mood swings, and seriousness of
      risk factors. The training programme should be tailor made and based on
      evaluation of the patient's adaptation to effort, in terms of frequency,
      intensity and duration of the exercises. Various types of exercise include
      overall or segmental physical training; concentric, eccentric, even isokinetic
      muscle contraction exercises; and proprioceptive rehabilitation. However,
      knowledge is lacking about the molecular mechanisms of the effects of training,
      the most effective intensity of effort, and strategies to develop physical
      activity in this ever-growing population for both primary and secondary
      prevention.

PMID- 17445932
TI  - [Abdominal obesity and knee ostheoarthritis].
AB  - The objective of our study was to determine whether waist circumference (WC) is a
      more reliable indicator than body mass index (BMI) of the presence of knee
      osteoarthritis in obese subjects. PATIENTS AND METHODS: We performed an
      observational study of obese patients with no other risk factors for knee
      osteoarthritis. For each patient, we evaluated BMI, WC, duration of obesity and
      knee pain. Two groups were identified: "asymptomatic patients" (AG), without knee
      pain, and "symptomatic patients" (SG). For the SG, we measured pain intensity
      (visual analog scale [VAS], 0-100 mm) and functional repercussions (using the
      Lequesne and WOMAC indexes). Patients with knee pain underwent standard
      radiographic procedures to search for signs of osteoarthritis, and the SG was
      divided into two subgroups: with radiological signs of osteoarthritis (SG-1) and
      without radiological signs of osteoarthritis (SG-2). The AG and SG groups and SG
      1 and SG-2 groups were compared for age, sex, and duration of obesity.
      Comparisons of BMI, WC, and function involved the Student's t-test. RESULTS: We
      recruited 56 patients for the study (82.5% females; mean obesity duration (13+/
      6.5 years; mean age 43.21+/-9.58 years). The mean BMI was 39.6+/-7.23 kg/m(2) and
      mean WC was 113+/-14.3 cm. We found 33 patients (59%) with knee pain. Independent
      of age, sex, duration of obesity and BMI, the SG showed more significant WC
      (117.27+/-14.71 cm vs. 107+/-11.75 cm for the AG, P 0.01). In the same group and
      independent of the already mentioned factors, the patients with radiological
      signs of osteoarthritis showed significant WC [122+/-15.57 cm (SG-1) vs. 108+/
      6.88 cm (SG-2) (P 0.01)]. Moreover, the VAS score of pain at rest and during
      effort and the WOMAC and Lequesne scores were 16+/-25.7 mm, 75+/-18.3 mm, 12.3+/
      8.92 and 11.5+/-5.44 (SG-1) and 7+/-18.4 mm, 70+/-19.2 mm, 5.7+/-3.05, and 6.9+/
      3.79 (SG-2), respectively. The difference between SG-1 and SG-2 was significant
      only for the WOMAC (P=0.015) and Lequesne (P=0.026) scores. CONCLUSION:
      Independent of BMI, WC appears to be a factor associated with the presence of
      knee pain and osteoarthritis in obese patients. Furthermore, a high WC is
      associated with significant functional repercussion.

PMID- 17445933
TI  - A comparison of mealtime insulin aspart and human insulin in combination with
      metformin in type 2 diabetes patients.
AB  - This randomized, open-label, cross-over study compares the efficacy of mealtime
      rapid-acting analog insulin aspart with human insulin, in combination with
      metformin. A total of 30 patients with type 2 diabetes, inadequately controlled
      (HbA(1c)>7.5%) with oral hypoglycemic agents (OHAs), were assigned to human
      insulin 30 min before meals or aspart immediately before meals, both with
      metformin 500 mg t.i.d. for 90 days. Patients then switched to the alternate
      insulin. At 90 and 180 days, blood glucose and lipids were measured at baseline
      and every 30 min after test meals, for 3h. HbA(1c) and hypoglycemic events were
      also assessed. After 3 months, HbA(1c) was significantly reduced with aspart, but
      not human insulin (-0.4+/-0.7% versus +0.1+/-0.7%, p<0.05). During meal tests,
      blood glucose area under the curve (AUC) was significantly lower with aspart than
      human insulin (1240+/-476 min/mmol/l versus 1588+/-766 min/mmol/l, p<0.01). AUCs
      for lipids were similar for both treatments. Neither group experienced serious
      hypoglycemic events. These results encourage treatment with mealtime insulin
      aspart plus metformin, in type 2 diabetes patients with postprandial
      hyperglycemia inadequately controlled by OHAs alone.

PMID- 17445934
TI  - Pediatric nonalcoholic fatty liver disease (NAFLD): a "growing" problem?
AB  - Nonalcoholic fatty liver disease (NAFLD) can affect both adults and children.
      With the current worldwide epidemic of pediatric obesity, pediatric NAFLD is
      increasingly being diagnosed. It is not exactly identical to NAFLD in adults, and
      these differences may be due in part to the occurrence of hepatic metabolic
      derangements typical of NAFLD during periods of active growth (infancy, mid
      childhood and puberty). The natural history of pediatric NAFLD is not yet known;
      however, children with pediatric NAFLD can develop cirrhosis. Although details of
      disease mechanism in pediatric NAFLD remain unclear, hyperinsulinemia with
      insulin resistance appears to be critical. Determining the pathogenesis of
      pediatric NAFLD is likely to enhance our understanding of NAFLD in all age groups
      and may identify new treatment opportunities. Finding effective ways to prevent
      pediatric NAFLD is an important issue for children's health.

PMID- 17445935
TI  - Vaptans: a promising therapy in the management of advanced cirrhosis.
AB  - BACKGROUND/AIMS: Hyponatremia (serum sodium concentration, <135 mmol/L) is a
      predictor of death among patients with chronic heart failure and cirrhosis. At
      present, therapy for acute and chronic hyponatremia is often ineffective and
      poorly tolerated. We investigated whether tolvaptan, an orally active vasopressin
      V(2)-receptor antagonist that promotes aquaresis--excretion of electrolyte-free
      water--might be of benefit in hyponatremia. METHODS: In two multicenter,
      randomized, double-blind, placebo-controlled trials, the efficacy of tolvaptan
      was evaluated in patients with euvolemic or hypervolemic hyponatremia. Patients
      were randomly assigned to oral placebo (223 patients) or oral tolvaptan (225) at
      a dose of 15mg daily. The dose of tolvaptan was increased to 30 mg daily and then
      to 60 mg daily, if necessary, on the basis of serum sodium concentrations. The
      two primary end points for all patients were the change in the average daily area
      under the curve for the serum sodium concentration from baseline to day 4 and the
      change from baseline to day 30. RESULTS: Serum sodium concentrations increased
      more in the tolvaptan group than in the placebo group during the first 4 days
      (P<0.001) and after the full 30 days of therapy (P<0.001). The condition of
      patients with mild or marked hyponatremia improved (P<0.001 for all comparisons).
      During the week after discontinuation of tolvaptan on day 30, hyponatremia
      recurred. Side effects associated with tolvaptan included increased thirst, dry
      mouth, and increased urination. A planned analysis that combined the two trials
      showed significant improvement from baseline to day 30 in the tolvaptan group
      according to scores on the Mental Component of the Medical Outcomes Study 12-item
      Short-Form General Health Survey. CONCLUSIONS: In patients with euvolemic or
      hypervolemic hyponatremia, tolvaptan, an oral vasopressin V2-receptor antagonist,
      was effective in increasing serum sodium concentrations at day 4 and day 30.
      [Abstract reproduced by permission of N Engl J Med 2006;355:2099-2112].

PMID- 17445936
TI  - Ribavirin in the treatment of recurrent hepatitis C after liver transplantation:
      difficult to manage but essential for success.

PMID- 17445937
TI  - Dangerous liaisons: drug, host and the environment.

PMID- 17445938
TI  - Hepatitis C virus: the viral way to fatty liver.

PMID- 17445939
TI  - Genetics in liver diseases.
AB  - In recent years, few fields in medicine have witnessed discoveries as momentous
      as those pertaining to the liver. Dramatic advances have been made, particularly
      in the areas of molecular biology and genetics. A joint EASL/AASLD Monothematic
      Conference was held on June 23rd-24th, 2006, in Modena, Italy, to bring the
      latest breakthroughs in different fields of genetics to hepatologists. This
      article reports the highlights of the conference and summarizes the main
      conclusions and implications for clinical and experimental hepatology.

PMID- 17445940
TI  - Fatigue in cholestatic liver disease: is it all in the mind?

PMID- 17445941
TI  - Do not trivialize the Fibroscan examination, value its accuracy.

PMID- 17445942
TI  - Impact of SARS on healthcare utilization by disease categories: implications for
      delivery of healthcare services.
AB  - OBJECTIVE: To assess the impact of the SARS epidemics in Taiwan on ambulatory
      care and inpatient utilization by disease categories and accreditation levels of
      hospital. METHODS: The National Health Insurance claims data of Taipei were
      analyzed. We calculated the changes in utilization between June 2002 and June
      2003 to estimate the impact that SARS had on utilization. RESULTS: The top three
      disease categories with the most significant drop in utilization were
      gastroenteritis (-53%), acute bronchitis (-45%), and tonsillitis (-40%) in
      ambulatory care and acute bronchitis (-82%), gastroenteritis (-72%), and
      pneumonia (-64%) in inpatient care. On the other hand, the disease categories
      with the smallest reduction were allergic reactions (-4%), skin infections (-6%),
      and anxiety (-10%) in ambulatory care and respiratory failure (+40%), delivery (
      2%), and fractures of lower limbs (-5%) in inpatient care. CONCLUSIONS: Disease
      categories could be classified into three groups according to the extent of
      change in utilization during the SARS outbreaks. Diseases with a prominent
      reduction were respiratory diseases, minor problems, and elective procedures.
      Diseases with a moderate reduction were mainly chronic diseases. Diseases with a
      limited reduction were acute conditions, difficult mental disorders, or
      procedures that could not be postponed. The utilization of some diseases shifted
      significantly from medical centers to district hospitals or clinics.

PMID- 17445944
TI  - Using results of eye movement signal analysis in the neural network recognition
      of otoneurological patients.
AB  - We extracted a collection of eye movement signals employed for almost two decades
      in clinical otoneurological tests at a balance laboratory. During those years we
      designed and programmed signal analysis methods to analyse their features in
      detail and to compute medically important attributes. In the present study, using
      such attributes and their results computed we classified test cases into groups
      of healthy subjects and patients with multilayer perceptron neural networks.
      Classification succeeded in total accuracies from 60% to 90% depending on the
      type of eye movements, which were saccades, nystagmus, sinusoidal movements and
      vestibulo-ocular reflex stimulated in two different ways; these are the chief eye
      movement tests applied in otoneurology.

PMID- 17445943
TI  - Silencing by imprinted noncoding RNAs: is transcription the answer?
AB  - Non-coding RNAs (ncRNAs) with gene regulatory functions are starting to be seen
      as a common feature of mammalian gene regulation with the discovery that most of
      the transcriptome is ncRNA. The prototype has long been the Xist ncRNA, which
      induces X-chromosome inactivation in female cells. However, a new paradigm is
      emerging--the silencing of imprinted gene clusters by long ncRNAs. Here, we
      review models by which imprinted ncRNAs could function. We argue that an Xist
      like model is only one of many possible solutions and that imprinted ncRNAs could
      provide the better model for understanding the function of the new class of
      ncRNAs associated with non-imprinted mammalian genes.

PMID- 17445945
TI  - The benefits of using Guyton's model in a hypotensive control system.
AB  - In order to improve the intraoperative applications, this paper presents the
      advantages of using Guyton's model in hypotensive control system development. In
      this system, the mean arterial pressure is decreased and maintained at a low
      level during anaesthesia by controlling sodium nitroprusside infusion rate. The
      key of the study is to develop a physiological model of cardiovascular dynamics
      to present the mean arterial pressure response to sodium nitroprusside, which was
      considered as a linear model in most of known blood pressure control systems.
      Being linear, the previous models cannot accurately mimic a physiological system
      of human circulation, especially at deep hypotensive control with strong reaction
      of the body. The enhanced model in this study was modified based on Guyton's
      model of human circulation. It is useful to design a PID controller, which allows
      studying and handling the wide range of the body sensitivities. This model is
      also helpful for studying the behaviors of patients under anaesthesia conditions,
      such as the perfusion of organs and the reaction of the body at hypotensive
      state. A fuzzy gain scheduler and a supervising algorithm were also developed for
      online tuning the controller to handle the behavior of the body. The control
      system was tested on 25 experiments on seven pigs in the animal laboratory.
      Simulation and experiment results proved the usefulness of Guyton's model in
      control system design which can present the dynamical response of blood pressure
      in the circulation under and after hypotensive control. The results also
      indicated the safety and stability of the controller.

PMID- 17445946
TI  - Pleural effusion in patients with non-small cell carcinoma--stage IV and not T4.

PMID- 17445947
TI  - Prevalence and associated factors with sunscreen use in Southern Brazil: A
      population-based study.
AB  - BACKGROUND: Sunscreen use is important for the prevention of skin cancer, but
      population-based information about its prevalence and associated factors are
      scarce in Brazil. OBJECTIVE: We sought to evaluate the prevalence and associated
      factors with sunscreen use among Brazilian adults. METHODS: We conducted a cross
      sectional population-based study with a representative sample of adults aged 20
      years or older living in the urban area of the city of Pelotas, Southern Brazil.
      We evaluated sunscreen use at the beach, at work, and during outdoor sports, for
      at least 20 minutes between 10 am and 4 Pm, from December 2004 to March 2005. The
      outcome measure was dichotomized in individuals who never used sunscreen, and
      those who used sunscreen, regardless of frequency. RESULTS: Prevalence of
      sunscreen use at the beach, work, and outdoor sports was 60.8% (95% confidence
      interval 55.6-66.0), 13.7% (95% confidence interval 10.7-16.6%), and 30.2% (95%
      confidence interval 24.1-36.3), respectively. At work, the median number of days
      of exposure was 70 days, whereas at the beach it was 10, and for sports it was
      16. Women, whites, those with higher educational achievement, and those with
      higher income were more likely to use sunscreen. LIMITATIONS: No data on adequacy
      of sunscreen use were gathered. CONCLUSION: Our data show that the individuals
      most exposed to sunlight are those who use sunscreen the least. Interventions
      targeting this group are required, because this is also the population with the
      lowest socioeconomic level.

PMID- 17445948
TI  - A pilot quality-of-life instrument for acne rosacea.
AB  - BACKGROUND: No rosacea-specific quality-of-life (QOL) instrument exists.
      OBJECTIVE: We sought to develop a validated, reliable rosacea-specific
      instrument. METHODS: From 6 in-depth interviews, we composed 21 rosacea-specific
      items. These items and Skindex-29 were administered in a validation cohort (n =
      59). Internal consistency reliability and reproducibility were measured with
      Cronbach's coefficient alpha and intraclass correlation coefficient,
      respectively. Responsiveness was assessed comparing baseline with 4- to 6-month
      responses. Construct validity was assessed with principal axes factor analyses.
      Discriminant validity was examined with an additional 38 patients comparing
      differences in responsiveness between the rosacea-specific QOL instrument and
      Skindex. RESULTS: Reliability was high (Cronbach's alpha: 0.82-0.97, intraclass
      correlation coefficient: 0.70-0.95). The rosacea-specific QOL instrument showed
      preliminary responsiveness for patients with improved disease (P <or= .05).
      Principal axes factor analyses correlated to hypothesized scales (r = 0.57-0.82).
      Discriminant validity was illustrated with greater differences in responsiveness
      using the rosacea-specific QOL instrument (P = .008). LIMITATIONS: Potential
      selection bias and lack of generalizability was a limitation. CONCLUSIONS: The
      rosacea-specific QOL instrument, RosaQoL, appears to be a reliable and valid QOL
      instrument and shows preliminary responsiveness for patients with improving
      rosacea.

PMID- 17445949
TI  - Oligoanalgesia in the emergency department: short-term beneficial effects of an
      education program on acute pain.
AB  - STUDY OBJECTIVE: Acute pain is the most frequent complaint in emergency
      department (ED) admissions, but its management is often neglected, placing
      patients at risk of oligoanalgesia. We evaluate the effect of the implementation
      of guidelines for pain management in ED patients with pain at admission or
      anytime during their stay in our ED. METHODS: This prospective pre-post
      intervention cohort study included data collection both before and after
      guideline implementation. Consecutive adult patients admitted with acute pain
      from any cause or with pain at any time after admission were enrolled. The
      quality of pain management was evaluated according to information in the ED
      medical records by using a standardized collection form, and its impact on
      patients was recorded with a questionnaire at discharge. RESULTS: Two hundred
      forty-nine and 192 patients were included during pre- and postintervention
      periods. Pain was documented in 61% and 76% of nurse and physician notes,
      respectively, versus 78% and 85% after the intervention (difference 17%/9%; 95%
      confidence interval [CI] 8% to 26%/2% to 17%, respectively). Administration of
      analgesia increased from 40% to 63% (difference 23%; 95% CI 13% to 32%) and of
      morphine from 10% to 27% (difference 17%; 95% CI 10% to 24%). Mean doses of
      intravenous morphine increased from 2.4 mg (95% CI 1.9 to 2.9 mg) to 4.6 mg (95%
      CI 3.9 to 5.3 mg); administration of nonsteroidal antiinflammatory drugs and
      acetaminophen increased as well. There was a greater reduction of visual analogue
      scale score after intervention: 2.1 cm (95% CI 1.7 to 2.4 cm) versus 2.9 cm (95%
      CI 2.5 to 3.3 cm), which was associated with improved patient satisfaction.
      CONCLUSION: Education program and guidelines implementation for pain management
      lead to improved pain management, analgesia, and patient satisfaction in the ED.

PMID- 17445950
TI  - Synthesis of amphiphilic galactopyranosyl diamines and amino alcohols as
      antitubercular agents.
AB  - Mono- and diacylated derivatives of galactopyranosyl amines were obtained from d
      galactose, via aminated intermediates prepared by reaction of 6-deoxy-6-iodo
      1,2:3,4-di-O-isopropylidene-alpha-d-galactopyranose with 1,3-propanediamine, 1,2
      ethanediamine or ethanolamine. Monoacylated derivatives displayed antitubercular
      activity.

PMID- 17445951
TI  - Synthesis and evaluation of new difluoromethyl azoles as antileishmanial agents.
AB  - Several compounds of great pharmacological interest contain the triazole and
      imidazole rings. In order to find new drugs with antileishmanial activity we have
      synthesized and evaluated new imidazole and triazole compounds carrying either
      the carbaldehyde or the difluoromethylene functionalities against promastigote
      forms of Leishmania amazonensis. Among the compounds tested difluoromethylene
      azoles 4b and 8f have inhibited the parasite growth significantly. Our results
      show that the introduction of the difluoromethylene moieties has turned the
      inactive carbaldehydes into active antileishmanial compounds.

PMID- 17445952
TI  - [Sarcoidosis demonstrated by fluorodeoxyglucose positron emission tomography in a
      case of granulomatous myopathy].
AB  - INTRODUCTION: Granulomatous myositis is a rare condition that has been described
      in association with sarcoidosis. In the absence of sarcoidosis or other
      underlying disease, a diagnosis of isolated granulomatous myositis is considered.
      OBSERVATION: A 61-year-old African man presented with progressive limitation in
      running and proximal atrophy of the lower limbs for the past year. Quadricipital
      muscle biopsy revealed non-caseating epithelioid granulomas and multinuclear
      giant cells. Whole body fluorodeoxyglucose positron emission tomography ((18)FDG
      PET) revealed hypermetabolic activity of salivary and lachrymal glands, and mild
      hypermetabolism in the mediastinal lymph nodes. Minor salivary gland biopsy was
      consistent with sarcoidosis. CONCLUSION: To our knowledge, this is the first
      reported case of sarcoid myopathy demonstrating the diagnostic usefulness of
      (18)FDG-PET.

PMID- 17445953
TI  - [Hepcidin and iron metabolism].
AB  - INTRODUCTION: In mammals, iron balance is maintained by regulating intestinal
      iron absorption and iron recycling by macrophages. EXEGESIS: The central role of
      hepcidin in the establishment of iron deficiency or overload has been revealed by
      the study of murine models. CONCLUSION: Many hopes have emerged from the
      discovery of hepcidin, pointing to potential treatments for hemochromatosis and
      anemia of inflammation (anemia of chronic disease).

PMID- 17445954
TI  - The effect of nurse training on the improvement of intravenous applications.
AB  - This research was performed to determine the effect of training on intravenous
      applications. The research was conducted between March 2004 and December 2004 as
      a single group pre-test, post-test, quasi- experimental design. The study
      population was composed of 45 volunteer nurses working in pediatric clinics of
      three hospitals at Erzurum city, in eastern Turkey. There was no sampling: the
      research was started with 45 nurses and completed with 40 nurses. Results of the
      research indicate that after the nurse training there has been a noticeable
      improvement in the following practices: intravenous peripheral catheter
      application skills, handwashing, glove wearing, antiseptic use, collaboration
      with the child, choice of cannula appropriate for the treatment, adequate
      securement with tape, record keeping of cannula placement time, informing the
      parents of the reason for cannula placement and the duration of treatment,
      informing the parents that it will not affect the mobility of the child and that
      the nurse can be notified in case of pain or discomfort following the procedure.
      These results may be useful in determining the weaknesses in the nurses'
      performance and planning their training accordingly.

PMID- 17445955
TI  - Modeling the long-term antibody response of a human papillomavirus (HPV) virus
      like particle (VLP) type 16 prophylactic vaccine.
AB  - The duration over which antibody responses persist following HPV vaccination is
      unknown. To estimate the longevity of responses induced by HPV-16 vaccination,
      two models were fitted to serum anti-HPV-16 levels measured during a 48-month
      study period. The first was a conventional model of antibody decay and the second
      was a modified model that accounts for long-lived immune memory. Using the
      antibody decay model, it was estimated that following administration of a three
      dose regimen of HPV-16 vaccine in women aged 16-23 years, anti-HPV-16 levels will
      remain above those induced naturally by HPV-16 infection for 12 years, and above
      detectable levels for 32 years in 50% of vaccinees. With the modified model,
      which fitted the data better (p<0.001), it was estimated that near life-long
      persistence of anti-HPV-16 following vaccination is expected at titer levels
      above those associated with reduction of natural HPV-16 infection in 76% of these
      subjects, and above detectable levels in 99% of these subjects.

PMID- 17445956
TI  - Development of a multi-mimotope peptide as a vaccine immunogen for infectious
      bursal disease virus.
AB  - To explore the mimotope vaccine approach against infectious bursal disease virus
      (IBDV), five IBDV-specific monoclonal antibodies (mAbs) were prepared and their
      binding peptides were screened against a phage-displayed 12-mer peptide library.
      After three rounds of biopanning, 12 phages were selected for each mAbs and their
      specificity to IBDV was verified by sandwich and competitive inhibition ELISAs.
      Seven phages per mAb were sequenced and their amino acid sequences were deduced.
      The five representative sequences of mimotopes corresponding mAbs were
      determined. An artificial gene, designated 5epis (5 epitopes) and consisting of
      the five mimotopes arranged in tandem (F1-F7-B34-2B1-2G8) with four GGGS spacers,
      was chemically synthesized and cloned into a prokaryotic expression plasmid
      pET28b. The protein, designated r5EPIS, was efficiently expressed in Escherichia
      coli and showed a size of 10kDa in SDS-PAGE. The r5EPIS protein reacted with anti
      IBDV mAbs and polyclonal antibodies in Western blot immunoassays. Immunization of
      SPF chickens with r5EPIS protein (with Freund adjuvant, 50mug per injection on
      day 0 and 14) evoked high levels of antibody (12,800 by ELISA/1600 by virus
      neutralizing assay at day 21) and protected 100% of the chickens against a
      challenge of 200 ELD(50) of IBDV GX8/99 strain, which sharply contrasted with
      the, respectively, 13.3% and 6.6% survival rate in the adjuvant group and the
      untreated group. The multi-mimotope protein r5EPIS promises to be a novel subunit
      vaccine candidate for IBDV.

PMID- 17445957
TI  - Immune responses of pigs to commercialized emulsion FMD vaccines and live virus
      challenge.
AB  - The immune response to structural and non-structural proteins (NSPs) was studied
      on sequential serum samples in swine from O/Taiwan/97 FMDV challenge studies,
      outbreaks and after vaccination. The results showed that pigs vaccinated with a
      commercial vaccine prior to or after infection maintained high neutralizing
      antibody titers with gradual decline from peak titers over the duration of this
      study. However, neutralizing antibody titers in non-vaccinated pigs only reached
      moderate levels 2-4 weeks post infection and remained low thereafter. For the 3B
      and 3ABC NSP antibody ELISA responses, there were gradually decreasing levels of
      NSP antibody over time. In multiple vaccinations, all pigs showed significant
      increases in neutralizing antibodies after booster vaccination. For the 3B NSP
      antibody ELISA after vaccination, the mean S/P ratios for pigs vaccinated with
      all three FMD vaccines were all below the 0.23 cut-off value set by the
      manufacture, but some sera from individual vaccinated pigs gave results above
      this cut-off after primary or secondary vaccination. However, with the 3ABC NSP
      antibody ELISA, all sera from vaccinated pigs had negative results for NSP
      antibody for all time points.

PMID- 17445958
TI  - Acceleration of selenium volatilization in seleniferous agricultural drainage
      sediments amended with methionine and casein.
AB  - Phytoremediation is potentially effective for managing excessive selenium (Se) in
      drainage sediment residing in the San Luis Drain in central California. This 2
      year field study examined the feasibility of amending drainage sediment
      (containing 4.78microgSeg(-1)) with methionine and casein to enhance
      volatilization without or with vegetation of Sporobolus airoides. Results show
      that without organic amendments, rates of Se volatilization were less than
      25microgm(-2)d(-1) in all plots. After amending the sediment with
      71.4mgmethioninekg(-1) soil, Se volatilization rates were 434+/-107microgm(-2)d(
      1) in vegetated plots and 289+/-117microgm(-2)d(-1) in irrigated bare plots. With
      the amendment of 572mgcaseinkg(-1) soil, rates increased to 346+/-103microgm(
      2)d(-1) in irrigated bare plots and to 114+/-55microgm(-2)d(-1) in vegetated
      plots. Both methionine and casein promoted biological remediation of Se via
      volatilization most effectively during the warmest months.

PMID- 17445959
TI  - Microbial processes as key drivers for metal (im)mobilization along a redox
      gradient in the saturated zone.
AB  - Two sites representing different aquifer types, i.e., Dommel (sandy) and Flemalle
      (gravelly loam) along the Meuse River, have been selected to conduct microcosm
      experiments. Various conditions ranging from aerobic over nitrate- to sulphate
      reducing were imposed. For the sandy aquifer, nitrate reducing conditions
      predominated, which specifically in the presence of a carbon source led to pH
      increases and enhanced Zn removal. For the calcareous gravelly loam, sulphate
      reduction was dominant resulting in immobilization of both Zn and Cd. For both
      aquifer types and almost all redox conditions, higher arsenic concentrations were
      measured in the groundwater. Analyses of different specific microbial populations
      by polymerase chain reaction (PCR) revealed the dominance of denitrifiers for the
      Dommel site, while sulfate reducing bacteria (SRB) were the prevailing population
      for all redox conditions in the Flemalle samples.

PMID- 17445960
TI  - ISG20, an actor of the innate immune response.
AB  - The interferon (IFN) system is a major effector of the innate immunity that
      allows time for the subsequent establishment of an adaptive immune response
      against wide-range pathogens. The effectiveness of IFN to control initial
      infection requires the cooperation between several pathways induced in the target
      cells. Recent studies that highlight the implication of the 3'-5' exonuclease
      ISG20 (IFN Stimulated Gene product of 20 kDa) in the host's defenses against
      pathogens are summarised in this review.

PMID- 17445961
TI  - Issues for small businesses with waste management.
AB  - Participation by small and medium enterprise (SME) in corporate social
      responsibility issues has been found to be lacking. This is a critical issue, as
      individually SMEs may have little impact on the environment but their collective
      footprint is significant. The management style and ethical stance of the owner
      manager affects business decision making and therefore has a direct impact on the
      environmental actions of the business. Although adoption of environmental
      practices to create competitive advantage has been advocated, many businesses see
      implementation as a cost which cannot be transferred to their customers. After a
      brief review of pertinent literature this paper reports on an exploratory
      investigation into the issue. Results show that whereas owner-managers of small
      enterprises express concern regarding the environment, this does not then
      translate into better waste management practices.

PMID- 17445962
TI  - Validation of 3D ultrasound vessel wall volume: an imaging phenotype of carotid
      atherosclerosis.
AB  - Carotid atherosclerotic lesions are a major cause of stroke and the
      identification and quantification of such lesions in patients is important for
      the development of a better understanding of atherogenesis in high risk
      populations and for the design of studies to assess treatment efficacy. Our
      objective was to develop and validate a new three-dimensional ultrasound (3DUS)
      measurement or phenotype of carotid atherosclerosis, vessel wall volume (VWV),
      which is a three-dimensional measurement of vessel wall thickness and plaque
      within the carotid arteries measured in 3DUS images. To assess both intraobserver
      and interscan variability, 3DUS images were acquired from the right and left
      carotid arteries of ten subjects with carotid atherosclerosis scanned twice
      within a period of 2 wk. For both VWV and total plaque volume (TPV), an expert
      observer performed five measurement trials of all images acquired at baseline
      scan and 2-wk rescan with a 5-d period between measurement trials for images.
      Images were re-randomized for each measurement trial and both TPV and VWV were
      measured by observers who were blinded to subject identification for each time
      point measurement. Coefficients of variation (COV) and intraclass correlation
      coefficients (ICC), for VWV measurements indicated higher intraobserver (scan COV
      = 4.6% ICC = 0.95, rescan COV = 3.4%, ICC = 0.96) and interscan reproducibility
      (COV = 5.7%, ICC = 0.85) than TPV measurements (intraobserver variability scan
      COV = 22.7% ICC = 0.85, rescan COV = 21.1% ICC = 0.88 and interscan variability,
      COV = 31.1%, ICC = 0.83), although absolute variances for both phenotypes were
      very similar (VWV = 90 mm3, TPV = 80 mm3).

PMID- 17445963
TI  - Analysis of internal jugular vein insufficiency--a comparison of two ultrasound
      methods.
AB  - Jugular venous valve insufficiency is a contributing factor to different
      pathologic conditions. For assessment of insufficiency, two ultrasound techniques
      have been developed, that are based on very different methodology (direct Doppler
      assessment versus air contrast ultrasound venography [ACUV]). This study was
      conducted to compare these two methods to improve comparability of existing
      studies and diagnostic accuracy in future studies. The function of 40 valves was
      determined in 20 individuals during a Valsalva maneuver. For direct Doppler
      assessment, valvular competence was assessed on basis of Doppler recordings,
      following recently established criteria. Valvular insufficiency in ACUV was
      diagnosed when reflux of an air-based echo contrast agent through the valve could
      be detected. With both methods, evaluation of 39 valves was accomplished (one
      exclusion due to hypoplasia of the corresponding vein). Both methods showed very
      high agreement in detection rates. All 18 valves being classified as insufficient
      by Doppler criteria were also insufficient in ACUV. Of 21 valves classified as
      competent (Doppler), one valve was rated as insufficient in ACUV due to discrete
      reflux of microbubbles. However, ACUV was inaccurate in evaluation of the left
      internal jugular vein after injection of the contrast agent into the right
      cubital vein. High detection rates could only be achieved when this was taken
      into account. This study shows that detection rates of internal jugular valve
      insufficiency are very similar with both methods. However, this high agreement
      required modification of the established protocol of ACUV.

PMID- 17445964
TI  - Can ultrasound propagate in the joint space of a human knee?
AB  - A large body of evidence supports the principle that the use of low-intensity
      pulsed ultrasound with a frequency of 1.5 MHz can reduce fracture healing time.
      It is hypothesized that similar therapeutic benefits may be achieved in damaged
      articular cartilage. This study looks specifically at a 22-mm circular ultrasound
      transducer delivering ultrasound with a frequency of 1.5 MHz. A human cadaver
      knee was imaged using CT, the resulting images were used to help map a number of
      hydrophone positions in the joint from which measurements were taken. The
      experimental results suggest that at best there is a 30-mm window in which to
      place the ultrasound transducer for ultrasound to propagate through the joint
      space. In terms of a clinical device delivering an I(SATA) of 30 mW cm(-2) to
      anterior regions of the joint, the I(SATA) in posterior regions will at best be
      in the region of 10 mW cm(-2). The clinical implications of this are not known
      and require further investigation.

PMID- 17445965
TI  - Wavelet-based signal processing of in vitro ultrasonic measurements at the
      proximal femur.
AB  - To estimate osteoporotic fracture risk, several techniques for quantitative
      ultrasound (QUS) measurements at peripheral sites have been developed. As these
      techniques are limited in the prediction of fracture risk of the central
      skeleton, such as the hip, we are developing a QUS device for direct measurements
      at the femur. In doing so, we noticed the necessity to improve the conventional
      signal processing because it failed in a considerable number of measurements due
      to multipath transmission. Two sets of excised human femurs (n = 6 + 34) were
      scanned in transmission mode. Instead of using the conventional methods, the
      radio-frequency signals were processed with the continuous wavelet transform to
      detect their time-of-flights for the calculation of speed-of-sound (SOS) in bone.
      The SOS-values were averaged over a region similar to the total hip region of
      dual X-ray absorptiometry (DXA) measurements and compared with bone mineral
      density (BMD) measured with DXA. Testing six standard wavelets, this algorithm
      failed for only 0% to 6% of scan in test set 1 compared with 29% when using
      conventional algorithms. For test set 2, it failed for 2% to 12% compared with
      approximately 40%. SOS and BMD correlated significantly in both test sets (test
      set 1: r2 = 0.87 to 0.92, p < 0.007; test set 2: r2 = 0.68 to 0.79, p < 0.0001).
      The correlations are comparable with correlations recently reported. However, the
      number of evaluable signals could be substantially increased, which improves the
      perspectives of the in vivo measurements.

PMID- 17445966
TI  - Enhanced targeting of ultrasound contrast agents using acoustic radiation force.
AB  - Contrast-enhanced ultrasound has shown significant promise as a molecular imaging
      modality. However, one potential drawback is the difficulty that ultrasound
      contrast agents (UCA) may have in achieving adhesion to target molecules on the
      vascular endothelium. Microbubble UCA exhibit a lateral migration toward the
      vessel axis in laminar flow, preventing UCA contact with the endothelium. In the
      current study, we have investigated low-amplitude acoustic radiation as a
      mechanism to move circulating UCA toward targeted endothelium. Intravital
      microscopy was used to assess the retention of microbubble UCA targeted to P
      selectin in the mouse cremaster microcirculation and femoral vessels. Acoustic
      treatment enhanced UCA retention to P-selectin four-fold in cremaster venules and
      in the femoral vein and 20-fold in the femoral artery. These results suggest
      acoustic treatment as a mechanism for enabling ultrasound-based molecular imaging
      in blood vessels with hemodynamic and anatomical conditions otherwise adversarial
      for UCA retention.

PMID- 17445967
TI  - Transient elastography using impulsive ultrasound radiation force: a preliminary
      comparison with surface palpation elastography.
AB  - The use of impulsive acoustic radiation force for transient strain imaging was
      investigated and compared with conventional elastography. A series of experiments
      were performed to evaluate the performances of the technique on gelatine phantoms
      containing inclusions and to determine a range of applications where radiation
      force elastography may be useful compared with static elastography. Slip
      boundaries and cylindrical inclusions of varying elastic modulus were placed in
      background materials. A focused ultrasound transducer was used to apply localised
      radiation force to a small volume of tissue mimic (100 mm3) for durations of 8
      ms. A conventional real-time ultrasound imaging probe was used to obtain radio-
      frequency echo signals. The resulting strains were mapped using ultrasound
      correlation-based methods. The instantaneous strain immediately following
      cessation of the radiation force was observed at depth within homogeneous gels
      and within stiff inclusions. The highly localised and transient strain that is
      produced at depth permits the sensing of variations in tissue elastic properties
      that are difficult to detect with conventional elastography, due to greater
      independence from boundary conditions. In particular, radiation force elastograms
      were more homogeneous in the background and within the inclusions and displayed a
      superior contrast-transfer-efficiency, particularly for regions that had negative
      modulus contrast or that were disconnected from the background or the anterior
      medium by a low friction boundary.

PMID- 17445968
TI  - Quantitative bone ultrasound at phalanges and calcaneus in osteoporotic
      postmenopausal women: influence of age and measurement site.
AB  - Phalangeal and calcaneal quantitative ultrasound (QUS) measurements were tested
      in a postmenopausal osteoporotic population of a wide age range to assess their
      ability to identify subjects with vertebral fractures in a population of
      postmenopausal women with osteoporosis. A group of 127 osteoporotic women aged
      from 50 to 85 y, who had been postmenopausal for at least 5 y, were enrolled. All
      subjects underwent phalangeal and calcaneal QUS measurements, femoral neck and
      lumbar spine dual energy X-ray absorptiometry (DXA) measurements and lateral
      thoracic and lumbar spine radiography. Osteoporosis was defined on the basis of
      femoral neck or lumbar spine bone mineral density (BMD) T-score lower than -2.5
      SD or of the presence of one or more vertebral atraumatic fractures,
      independently of BMD values. Fifty-two women had one or more vertebral fractures,
      while the remaining 75 had no evidence of previous fracture. Both QUS techniques
      were able to discriminate between fractured and nonfractured subjects in the
      whole group (p < 0.05). When patients aged <70 y (n = 43) and patients aged > or
      = 70 y (n = 84) were considered separately, phalangeal QUS and lumbar spine BMD
      were able to discriminate vertebral fractures in the younger group (p < 0.05),
      whereas calcaneal QUS was able to discriminate vertebral fractures in the older
      one (p < 0.05). The results of this study raise an issue of the optimal use of
      different QUS techniques and different skeletal sites in the management of
      osteoporosis in early or late postmenopausal life.

PMID- 17445969
TI  - Detection of the cardiac activation sequence by novel echocardiographic tissue
      tracking method.
AB  - Asynchronous cardiac activation leads to decreased pumping efficiency.
      Quantifying the activation sequence may optimize both the selection of patients
      for cardiac resynchronization therapy (CRT) and its efficacy. The feasibility of
      assessing the directivity and the degree of synchronous activation with
      ultrasound was examined. A tissue tracking method (CEB, GE-Ultrasound, AFI, GE
      Healthcare Inc., Wauwatosa, WI, USA) provided the regional strain profiles. The
      first maxima in systole of the regional circumferential strains were considered
      as the activation times. An integrative vector (SDV) describes the activation
      synchrony and directivity. In six open-chest sheep, activation maps and SDV were
      calculated in short-axis planes of the left ventricle for normal activation and
      induced pacings from the anterior and lateral free walls. Both magnitude and
      angle of the SDV were statistically different (p < 0.05) for the different
      pacings. Localization of the pacing site was 3 degrees +/- 18 degrees from true
      position. Conclusions were that motion analysis in echocardiograms provides
      insightful information regarding the activation process and may enhance
      procedures such as CRT.

PMID- 17445970
TI  - Ultrasound perfusion imaging: determination of thresholds for the identification
      of critically disturbed perfusion in acute ischemic stroke--a pilot study.
AB  - Ultrasound harmonic imaging of perfusion after ultrasound contrast agent (UCA)
      bolus injection (BHI) can detect cerebral perfusion deficits. In a pilot study,
      we evaluated the ability of time-intensity curve (TIC) measurements to
      differentiate between normal and hypoperfused brain areas in acute ischemic
      stroke. Ten patients with symptoms of acute middle cerebral artery infarction
      were investigated (SONOS 5500, Harmonic Imaging 1.6/3.8 MHz, diencephalic plane,
      10 cm investigation depth, SonoVue 2.4 mL bolus). Peak signal increase (PSI),
      time-to-peak intensity (TPI) and area under the curve (AUC) were calculated for
      60 regions-of-interest (ROIs) in each patient. Reference methods: Perfusion- and
      diffusion-weighted MRI (PWI/DWI) within 4 h before/after BHI (PWI threshold: 4
      s). Receiver operating characteristics (ROC) analysis defined cut-off values for
      each TIC variable to distinguish between normal and affected brain areas as
      defined by PWI/DWI. In five patients, PWI showed a perfusion delay >4 s; seven
      patients had a DWI lesion. In three patients, both PWI and DWI findings showed
      pathology; one patient had a normal MRI of the insonation plane. Cut-off values
      for PWI delay: PSI: 5.53% (sensitivity .98, specificity .89); TPI: 4.04 s
      (sensitivity .74, specificity .69) and AUC: .63 (sensitivity .94, specificity
      .58). Referred to the mean value in unaffected brain areas the relative
      thresholds were 17.6%, 109.5% and 16.1%, respectively. Regarding DWI, only for
      PSI, a significant cut-off value was defined: 10.86%, sensitivity .84,
      specificity .60 (34.6% of mean). In conclusion, these thresholds distinguish
      between normal and affected brain areas in acute ischemic stroke.

PMID- 17445971
TI  - Editorial comment on: prognostic and predictive factors in patients with androgen
      independent prostate cancer treated with docetaxel and estramustine: a single
      institution experience.

PMID- 17445972
TI  - Re: Silvano Gallus, Roberto Foschi, Eva Negri et al. Dietary zinc and prostate
      cancer risk: a case-control study from Italy. Eur urol 2007;52:1052-7.

PMID- 17445973
TI  - Can penile size be preserved after radical prostatectomy?

PMID- 17445974
TI  - Editorial comment on: prognostic and predictive factors in patients with androgen
      independent prostate cancer treated with docetaxel and estramustine: a single
      institution experience.

PMID- 17445975
TI  - Ejaculatory latency vs. patient-reported outcomes (PROs) as study end points in
      premature ejaculation clinical trials.

PMID- 17445976
TI  - Prognostic and predictive factors in patients with androgen-independent prostate
      cancer treated with docetaxel and estramustine: a single institution experience.
AB  - OBJECTIVES: To investigate potential prognostic and predictive factors in
      patients with androgen-independent prostate cancer (AIPC) treated with docetaxel
      chemotherapy. METHODS: This analysis included 94 consecutive AIPC patients who
      were treated between March 2001 and May 2006 with biweekly docetaxel 45 mg/m(2)
      (day 2) and estramustine 140 mg three dimes daily (days 1-3). RESULTS: Prostate
      specific antigen (PSA) responses were observed in 45 of 84 evaluable patients
      (53%), whereas objective responses were observed in 16 of 40 patients with
      measurable disease (40%). Median survival (OS) was 16.2 mo (95% confidence
      interval [CI], 12.9-19.4) and median time to PSA progression (TTP) 5.0 mo (95%CI,
      3.6-7.1). OS was independently associated with pain score baseline PSA and weight
      loss. Patients with only extraosseous disease had higher PSA response rate (87%
      vs. 49%, p=0.014) and superior TTP compared with patients with bone metastases
      with or without extraosseous disease (7.3 vs. 4.3 vs. 4 mo, p=0.002). Concurrent
      bone and extraosseous metastases were associated with worse prognosis compared
      with each site alone (median OS: 12.3 vs.19 vs.18.3 mo, p=0.007). CONCLUSIONS:
      Among patients with AIPC treated with biweekly docetaxel and estramustine,
      baseline PSA >100, existence of pain, weight loss, and simultaneous extraosseous
      and bone disease were associated with worse prognosis. Extraosseous metastases
      seem to be more sensitive than bone disease to this chemotherapy.

PMID- 17445977
TI  - Laparoscopic partial nephrectomy: what about hilar control?

PMID- 17445978
TI  - Is renal warm ischemia over 30 minutes during laparoscopic partial nephrectomy
      possible? One-year results of a prospective study.
AB  - OBJECTIVE: To evaluate renal damage and impairment of renal function 1 yr after
      laparoscopic partial nephrectomy (LPN) with warm ischemia >30 min. METHODS: From
      July 2004 to June 2005, 18 patients underwent LPN with warm ischemia time >30
      min. Kidney damage markers (daily proteinuria and tubular enzymes) and renal
      function (serum creatinine, cystatin C, and creatinine clearances) were assessed
      on postoperative days 1 and 5 and at 12 mo. Glomerular filtration rate (GFR) was
      evaluated before surgery and at 3 mo. Renal scintigraphy was performed before the
      procedure, at 5 d and at 3 and 12 mo postoperatively. Statistical analysis was
      performed using the Student t test and logistic regression analysis. RESULTS: In
      terms of kidney damage and renal function markers, the statistical analysis
      demonstrated that at 1 yr there was complete return to the normal range and no
      statistical difference between the values at the various time points. The GFR was
      not significantly different before and 3 mo after surgery. In terms of
      scintigraphy of the operated kidney, the values were 48.35+/-3.82% (40-50%)
      before the procedure, 36.88+/-8.42 (16-50%) on postoperative day 5 (p=0.0001),
      40.56+/-8.96 (20-50%) at 3 mo (p=0.003), and 42.8+/-7.2% (20-50%) 1 yr after
      surgery (p=0.001). CONCLUSION: Our results demonstrate that kidney damage occurs
      during LPN when warm ischemia is >30 min. This damage is only partially
      reversible and efforts should be made to keep warm ischemia within 30 min.

PMID- 17445980
TI  - Anaerobic ammonia removal in presence of organic matter: a novel route.
AB  - This study describes the feasibility of anaerobic ammonia removal process in
      presence of organic matter. Different sources of biomass collected from diverse
      eco-systems containing ammonia and organic matter (OM) were screened for
      potential anaerobic ammonia removal. Sequential batch studies confirmed the
      possibility of anaerobic ammonia removal in presence of OM, but ammonia was
      oxidized anoxically to nitrate (at oxidation reduction potential; ORP=-248+/-25
      mV) by an unknown mechanism unlike in the reported anammox process. The oxygen
      required for oxidation of ammonia might have been generated through catalase
      enzymatic activity of facultative anaerobes in mixed culture. The oxygen
      generation possibility by catalase enzyme route was demonstrated. Among the
      inorganic electron acceptors (NO(2)(-), NO(3)(-) and SO(4)(2-)) studied, NO(2)(-)
      was found to be most effective in total nitrogen removal. Denitrification by the
      developed culture was much effective and faster compared to ammonia oxidation.
      The results of this study show that anaerobic ammonia removal is feasible in
      presence of OM. The novel nitrogen removal route is hypothesized as enzymatic
      anoxic oxidation of NH(4)(+) to NO(3)(-), followed by denitrification via
      autotrophic and/or heterotrophic routes. The results of batch study were
      confirmed in continuous reactor operation.

PMID- 17445981
TI  - Spectrophotometric simultaneous determination of nitrophenol isomers by
      orthogonal signal correction and partial least squares.
AB  - A simple, novel and sensitive spectrophotometric method was described for
      simultaneous determination of nitrophenol isomers mixtures. All factors affecting
      on the sensitivity were optimized and the linear dynamic range for determination
      of nitrophenol isomers were found. The simultaneous determination of nitrophenol
      mixtures by using spectrophotometric methods is a difficult problem, due to the
      spectral interferences. The partial least squares modeling was used for the
      multivariate calibration of the spectrophotometric data. The orthogonal signal
      correction was used for preprocessing of data matrices and the prediction results
      of model, with and without using orthogonal signal correction, were statistically
      compared. The experimental calibration matrix was designed by measuring the
      absorbance over the range 300-520 nm for 21 samples of 1-20, 1-20 and 1-10 microg
      ml(-1) of m-nitrophenol, o-nitrophenol and p-nitrophenol, respectively. The RMSEP
      for m-nitrophenol, o-nitrophenol and p-nitrophenol with and without OSC were
      0.3682, 0.5965, 0.3408 and 0.7351, 0.9962, 1.0055, respectively. The proposed
      method was successfully applied for the determination of m-nitrophenol, o
      nitrophenol and p-nitrophenol in synthetic and real matrix samples such as water.

PMID- 17445982
TI  - Calculations of bond dissociation energies and dipole moments in energetic
      materials using density-functional methods.
AB  - We compare the effectiveness of six exchange/correlation functional combinations
      (Becke/Lee, Yang and Parr; Becke-3/Lee, Yang and Parr; Becke/Perdew-Wang 91;
      Becke-3/Perdew-Wang 91; Becke/Perdew 86; Becke-3/Perdew 86) for computing C-N, O
      O and N-NO2 dissociation energies and dipole moments of five compounds. The
      studied compounds are hexabydro-1,3,5-trinitro-1,3,5-triazine (RDX),
      dimethylnitramine, cyanogen, nitromethane and ozone. The Becke-3/Perdew 86 in
      conjunction with 6-31G** is found to give the best results, although for the
      dipole moments of RDX, there is a slightly difference that B3P86/6-31G** is less
      reliable than B3P86/6-31+G**.

PMID- 17445983
TI  - Application of nonlinear regression analysis for ammonium exchange by natural
      (Bigadic) clinoptilolite.
AB  - The experimental data of ammonium exchange by natural Bigadic clinoptilolite was
      evaluated using nonlinear regression analysis. Three two-parameters isotherm
      models (Langmuir, Freundlich and Temkin) and three three-parameters isotherm
      models (Redlich-Peterson, Sips and Khan) were used to analyse the equilibrium
      data. Fitting of isotherm models was determined using values of standard
      normalization error procedure (SNE) and coefficient of determination (R(2)).
      HYBRID error function provided lowest sum of normalized error and Khan model had
      better performance for modeling the equilibrium data. Thermodynamic investigation
      indicated that ammonium removal by clinoptilolite was favorable at lower
      temperatures and exothermic in nature.

PMID- 17445984
TI  - Central administration of neuromedin U suppresses food intake in chicks.
AB  - The appetite-suppressive action of brain-gut peptides is similar in both chickens
      and mammals. In mammals, the brain-gut peptide neuromedin U (NMU) suppresses food
      intake via hypothalamic neuropeptides, corticotropin-releasing factor (CRF),
      oxytocin, and arginine-vasopressin. In chickens, central administration of CRF,
      oxytocin, or arginine-vasotocin (AVT, a nonmammalian equivalent of arginine
      vasopressin) suppresses food intake. However, the anorexigenic action of NMU in
      chickens has not yet been identified. In the present study, we analyzed the
      effects of the central administration of NMU on food intake and hypothalamic mRNA
      levels of CRF, AVT and mesotocin (a nonmammalian equivalent of oxytocin) in
      chicks. Intracerebroventricular administration of NMU in chicks significantly
      suppressed food intake and induced wing-flapping behavior. NMU also significantly
      upregulated mRNA expression of CRF and AVT, but did not influence mRNA expression
      of mesotocin in the hypothalamus. These results suggest that NMU functions as an
      appetite-suppressive peptide via CRF and AVT in the central nervous system in
      chicks.

PMID- 17445985
TI  - New tomographic atom probe at University of Muenster, Germany.
AB  - Currently atom probe tomography provides the highest spatial resolution compared
      to all other volume analysis techniques. Owing to its single atom sensitivity, it
      is specially suited to study nano-structured materials. Therefore, a new atom
      probe was installed at the Institute for Material Physics at University of
      Muenster, Germany, to study thin film reactions. Since the available budget was
      rather limited, a cost-effective non-commercial atom probe was constructed. The
      instrument is based on a 2D delay line detector system of 120 mm diameter. To
      achieve a large collecting angle and thus large volumes of analysis, a straight
      flight tube without a reflectron is used. This way, the flight distance may be
      reduced down to 160 mm. However, the variable chamber layout allows using a
      reflectron as an alternative. Furthermore, a laser system is implemented that
      delivers pulses in the 500 ps range to make possible laser-assisted evaporation
      of atoms. The article describes instrumental details and presents first
      characteristic data.

PMID- 17445986
TI  - Electron irradiation-induced destruction of carbon nanotubes in electron
      microscopes.
AB  - Observations of carbon nanotubes under exposure to electron beam irradiation in
      standard transmission electron microscope (TEM) and scanning electron microscope
      (SEM) systems show that such treatment in some cases can cause severe damage of
      the nanotube structure, even at electron energies far below the approximate 100
      keV threshold for knock-on damage displacing carbon atoms in the graphene
      structure. We find that the damage we observe in one TEM can be avoided by use of
      a cold finger. This and the morphology of the damage imply that water vapour,
      which is present as a background gas in many vacuum chambers, can damage the
      nanotube structure through electron beam-induced chemical reactions. Though, the
      dependence on the background gas makes these observations specific for the
      presently used systems, the results demonstrate the importance of careful
      assessment of the level of subtle structural damage that the individual electron
      microscope system can do to nanostructures during standard use.

PMID- 17445987
TI  - Heterogeneity of glutamatergic and GABAergic release machinery in cerebral
      cortex.
AB  - We investigated whether cortical glutamatergic and GABAergic release machineries
      can be differentiated on the basis of the proteins they express, by studying the
      degree of co-localization of synapsin (SYN) I and II, synaptophysin (SYP) I and
      II, synaptosomal-associated protein (SNAP)-25 and SNAP-23 in vesicular glutamate
      transporter (VGLUT) 1-, VGLUT2- and vesicular GABA transporter (VGAT)-positive
      (+) puncta in the rat cerebral cortex. Co-localization studies showed that SYNI
      and II were expressed in approximately 90% of VGLUT1+, approximately 30% of
      VGLUT2+ and 30-50% of VGAT+ puncta; SYPI was expressed in approximately 95% of
      VGLUT1+, 30% of VGLUT2+, and 45% of VGAT+ puncta; SYPII in approximately 7% of
      VGLUT1+, 3% of VGLUT2+, and 20% of VGAT+ puncta; SNAP-25 in approximately 94% of
      VGLUT1+, 5% of VGLUT2+, and 1% of VGAT+ puncta, and SNAP-23 in approximately 3%
      of VGLUT1+, 86% of VGLUT2+, and 22% of VGAT+ puncta. Since SYPI, which is
      considered ubiquitous, was expressed in about half of GABAergic axon terminals,
      we studied its localization electron microscopically and in immunoisolated
      synaptic vesicles: these studies showed that approximately 30% of axon terminals
      forming symmetric synapses were SYPI-negative, and that immunoisolated VGAT
      positive synaptic vesicles were relatively depleted of SYPI as compared with
      VGLUT1+ vesicles. Overall, the present investigation shows that in the cerebral
      cortex of rats distinct presynaptic proteins involved in neurotransmitter release
      are differentially expressed in GABAergic and in the two major types of
      glutamatergic axon terminals in the cerebral cortex of rats.

PMID- 17445988
TI  - Opposing effects of intra-nucleus accumbens mu and kappa opioid agonists on
      sensory specific satiety.
AB  - Mu opioid (MOP) agonists acting in the nucleus accumbens (NAcc) robustly enhance
      consumption of palatable foods. In addition, the effect on consumption of
      palatable foods produced by MOP agonists acting in the NAcc depends on both
      recent flavor exposure and the availability of a choice between different
      flavored foods. In contrast, kappa opioid (KOP) agonists have variable effects on
      feeding and KOP agonists have MOP opposing behavioral actions when microinjected
      at several brain sites. We previously demonstrated that NAcc MOP agonists reverse
      the devaluation (satiety) effect of pre-feeding for a given flavor; in fact, NAcc
      MOP agonists selectively increase consumption of a recently sampled food. In
      contrast, in the present study, we found that the selective KOP agonist U50488
      injected into the NAcc of rats reduced consumption of a recently sampled flavor
      while increasing consumption of the flavor that was not pre-fed. Intra-NAcc
      U50488 did not affect overall consumption or flavor preference in the absence of
      pre-feeding. The present data, in conjunction with our previous findings,
      highlight the robust and opposing role of NAcc MOP and KOP opioid receptors in
      palatability-based food choice and consumption and raise the possibility that an
      endogenous KOP agonist acting in the NAcc contributes to the phenomenon of
      sensory specific satiety.

PMID- 17445989
TI  - Influence of peripheral nerve injury on response properties of locus coeruleus
      neurons and coeruleospinal antinociception in the rat.
AB  - Noradrenergic locus coeruleus (LC) is involved in pain regulation. We studied
      whether response properties of LC neurons or coeruleospinal antinociception are
      changed 10-14 days following development of experimental neuropathy. Experiments
      were performed in spinal nerve-ligated, sham-operated and unoperated male rats
      under sodium pentobarbital anesthesia. Recordings of LC neurons indicated that
      responses evoked by noxious somatic stimulation were enhanced in nerve-injured
      animals, while the effects of nerve injury on spontaneous activity or the
      response to noxious visceral stimulation were not significant. Microinjection of
      glutamate into the central nucleus of the amygdala produced a dose-related
      inhibition of the discharge rate of LC neurons in nerve-injured animals but no
      significant effect on discharge rates in control groups. Assessment of the heat
      induced hind limb withdrawal latency indicated that spinal antinociception
      induced by electrical stimulation of the LC was significantly weaker in nerve
      injured than control animals. The results indicate that peripheral neuropathy
      induces bidirectional changes in coeruleospinal inhibition of pain. Increased
      responses of LC neurons to noxious somatic stimulation are likely to promote
      feedback inhibition of neuropathic hypersensitivity, while the enhanced
      inhibition of the LC from the amygdala is likely to suppress noradrenergic pain
      inhibition and promote neuropathic pain. It is proposed that the decreased spinal
      antinociception induced by direct stimulation of the LC may be explained by
      pronociceptive changes in the non-noradrenergic systems previously described in
      peripheral neuropathy. Furthermore, we propose the hypothesis that emotions
      processed by the amygdala enhance pain due to increased inhibition of the LC in
      peripheral neuropathy.

PMID- 17445990
TI  - Oxidative damage of 14-3-3 zeta and gamma isoforms in Alzheimer's disease and
      cerebral amyloid angiopathy.
AB  - Previous studies have shown oxidative damage resulting from amyloid Abeta
      exposure to cultured cells and in murine models. A target of oxidation is 14-3-3
      which comprises a group of proteins involved in kinase activation and chaperone
      activity. The present study shows glycoxidative damage, as revealed with mono and
      bi-dimensional gel electrophoresis and Western blotting, followed by in-gel
      digestion and mass spectrometry, in the frontal cortex in Alzheimer's disease
      (AD) and cerebral amyloid angiopathy (CAA), a neurodegenerative disease with
      deposition of Abeta in cerebral blood vessels and in diffuse plaques
      unaccompanied by intraneuronal hyper-phosphorylated tau deposition.
      malondialdehyde-lysine (MDA-Lys)-, but not 4-hydroxy-2-nonenal (HNE)
      immunoreactive adducts, and N-carboxyethyl-lysine (CEL), but not N-carboxymethyl
      lysine (CML)-products, were present in 14-3-3 involving zeta and gamma isoforms
      in both AD and CAA. These findings demonstrate that 14-3-3 glyco- and
      lipoxidation occurs in AD and CAA, probably as a direct consequence of Abeta
      deposition.

PMID- 17445991
TI  - Memantine reduces oxidative damage and enhances long-term recognition memory in
      aged rats.
AB  - Many neurodegenerative diseases, including Alzheimer's (AD), Parkinson's (PD) and
      Huntington's diseases (HD), are caused by different mechanisms but may share a
      common pathway to neuronal injury as a result of the overstimulation of glutamate
      receptors. It has been suggested that this pathway can be involved in generation
      of cognitive deficits associated with normal aging. Previous studies performed in
      our laboratory have demonstrated that aged rats presented recognition memory
      deficits. The aim of the present study was to evaluate the effect of memantine, a
      low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist, on age-induced
      recognition memory deficits. Additionally, parameters of oxidative damage in
      cerebral regions related to memory formation were evaluated. In order to do that,
      male Wistar rats (24 months old) received daily injections of saline solution or
      memantine (20 mg/kg i.p.) during 21 days. The animals were submitted to a novel
      object recognition task 1 week after the last injection. Memantine-treated rats
      showed normal recognition memory while the saline group showed long-term
      recognition memory deficits. The results show that memantine is able to reverse
      age-induced recognition memory deficits. We also demonstrated that memantine
      reduced the oxidative damage to proteins in cortex and hippocampus, two important
      brain regions involved in memory formation. Thus, the present findings suggest
      that, at least in part, age-induced cognitive deficits are related to oxidative
      damage promoted by NMDA receptor overactivation.

PMID- 17445992
TI  - Unifying mechanism for bacterial cell signalers (4,5-dihydroxy-2,3-pentanedione,
      lactones and oligopeptides): electron transfer and reactive oxygen species.
      Practical medical features.
AB  - Cell signaling has attracted much attention involving higher organisms, and more
      recently is of considerable interest concerning involvement in the bacterial
      realm. Many aspects can apply, including quorum sensing. Of the participating
      molecules, designated autoinducers, 4,5-dihydroxy-2,3-pentanedione (DPD) is one
      of the most important. It is in equilibrium with a furanone and a furanosyl
      borate diester (AI-2). A prior hypothesis for cell signaling in higher organisms
      invoked a key role for electron transfer (ET) and reactive oxygen species (ROS),
      as well as conduits, relays and electrical effects. The principal ET
      functionalities are quinones, metal complexes, ArNO(2), and iminium species. A
      lesser known type is the alpha-dicarbonyl class. Diacetyl, a member, as well as
      its imine derivatives, can serve as a model for DPD, since the parent possesses a
      reduction potential amenable to ET in the biological domain. Hence, it is
      conceivable that DPD and its imine derivatives may be involved in ET-ROS
      processes. Presence of hydroxy groups should facilitate ET by DPD vs. diacetyl.
      Extensive prior literature supports participation of ET functionalities in action
      of therapeutic drugs, toxins and various illnesses. This biochemical behavior
      also applies to the alpha-dicarbonyl parent models. A second important bacterial
      autoinducer is the lactone category. Although ET functionality is lacking, the
      presence of the 1,3-dicarbonyl structure can provide a site for avid chelation
      with redox metal, e.g., iron or copper, followed by ET-ROS. Findings with added
      iron furnish support for the proposal. Oligopeptides comprise the third principal
      type of bacterial signaling agent. A prior review incorporates these within the
      theoretical framework based on ET by redox amino acids and redox enzymes. In
      recent years there has been a rapid increase in resistance to antibiotics by
      pathogenic bacteria. Infectious diseases are the leading cause of death worldwide
      and the third leading cause in the US. An alternate approach to antibiotics that
      are becoming less and less effective is to attenuate bacterial virulence.
      Bacterial infections appear to be importantly associated with biofilm formation.
      Since quorum sensors play a crucial role in this connection, they provide
      attractive targets for much-needed, novel approaches. Two of the main
      autoinducers investigated are the AHL and AI-2 systems. This review summarizes
      the literature, mostly recent, on this topic. Leads are provided by higher
      organisms that appear to have evolved means for disrupting bacterial cell
      communication and, hence, escape colonization. The main types in this category
      are the furanones, for which both natural and synthetic types have been
      investigated with promising results.

PMID- 17445993
TI  - Ghrelin: a novel peptide with therapeutic effect in certain cancers?

PMID- 17445994
TI  - How dietary restriction catalyzed the evolution of the human brain: An exposition
      of the nutritional neurotrophic neoteny theory.
AB  - The purpose of this theoretical treatise is to explain the evolution of human
      encephalization. The evolutionary expansion of the human brain is herein regarded
      as a single component of an interrelated complex encompassing depressed somatic
      and sexual development and increased longevity. These cardinal phenotypic
      features, termed the Quadripartite Complex, were selected for their adaptiveness
      amidst the environmental deterioration extant during the formative phase of human
      evolution--the Plio-Pleistocene period. This interval of environmental
      transformation inevitably eventuated in ecological alteration and dietary
      diminution. Suggestively, experimentally imposed dietary restriction routinely
      results in lengthened lifespan, delayed sexual maturation, depressed growth and
      increased encephalization as a concomitant consequence of body mass reduction and
      brain mass maintenance. Thus, dietary restriction ostensibly induces discernible
      metabolic adaptations whether incurred ontologically or evolutionarily. Several
      experiments indicate that dietary restriction promotes the preservation and
      generation of neurons via induction of neurotrophic factors. To the extent that
      neurogenesis is a molecular mediator of mental acuity, it is evident that
      nutrition and cognition are intimately linked. Extrapolating to an evolutionary
      context, increased intelligence ought to confer advantages to organisms enduring
      dietary deprivation insofar as increased intelligence ensures more facile food
      acquisition. This reasoning underlies the nutritional neurotrophic neoteny (N(3))
      theory, which holds that humans exhibit an altered pattern of neurotrophin
      expression resulting from positive selection for heightened intelligence amidst
      environmental deterioration and consequent dietary deficiency. The altered
      pattern of neurotrophin expression exhibited by humans, it is deduced, results in
      a protracted phase of developmental neurogenesis and a resultant retention of
      neurons that would otherwise be extirpated due to programmed cell death.
      Importantly, during neonatal neurogenesis mammals produce an excess number of
      neurons whose eventual destruction is dictated by neurotrophic factors. An
      altered pattern of neurotrophin expression during neurogenesis, as N(3) proposes,
      could therefore furnish a larger adult brain. As to how humans could afford to
      accrete exuberant neural tissue under conditions of chronic food scarcity the
      homo hypothalamic hypometabolism (H(3)) theory offers a plausible answer: reduced
      growth and delayed sexual maturation, mediated by the hypothalamus and its
      endocrine effectors, offset the energetic costs of increased encephalization in
      humans. H(3) is herein presented as a general theory of human evolution while
      N(3) may be regarded as a special theory of human encephalization.

PMID- 17445995
TI  - Psychological neoteny and higher education: associations with delayed parenthood.
AB  - In a recent Medical Hypotheses editorial, I suggested the name psychological
      neoteny (PN) to refer to the widely-observed phenomenon that adults in
      modernizing liberal democracies increasingly retain many of the attitudes and
      behaviors traditionally associated with youth. I further suggested that PN is a
      useful trait for both individuals and the culture in modernizing societies;
      because people need to be somewhat child-like in their psychology order to keep
      learning, developing and adapting to the rapid and accelerating pace of change.
      Thirdly, I put forward the hypothesis that the major cause of PN in modernizing
      societies is the prolonged duration of formal education. Here I present a
      preliminary empirical investigation of this hypothesis of psychological neoteny.
      Marriage and parenthood are indicative of making a choice to 'settle down' and
      thereby move on from the more flexible lifestyle of youth; and furthermore these
      are usually commitments which themselves induce a settling down and maturation of
      attitudes and behaviors. A sevenfold expansion of participation in UK higher
      education up to 2001 was reflected in delay in marriage and parenthood.
      Increasing number of years of education is quantitatively the most important
      predictor of increasing age of the mother at the time of her first birth: among
      women college graduates about half are aged 30 or older at the time of their
      first birth--a rise of 400% in 25 years. Parenthood is associated with a broad
      range of psychologically 'maturing' and socially-integrating effects in both men
      and women. However, the economic effect is different in men and women: after
      parenthood men are more likely to have a job and work more hours while women
      change in the opposite direction. The conclusion is that psychological neoteny is
      indeed increasing, and mainly as a consequence of the increasing percentage of
      school leavers going into higher education. But at present it is unclear whether
      this trend is overall beneficial or harmful; and the answer may be different for
      men and women.

PMID- 17445996
TI  - Sonocarcinogenesis: loud noise may cause malignant transformation of cells.

PMID- 17445997
TI  - Direct measurement of lung motion using hyperpolarized helium-3 MR tagging.
AB  - PURPOSE: To measure lung motion between end-inhalation and end-exhalation using a
      hyperpolarized helium-3 (HP (3)He) magnetic resonance (MR) tagging technique.
      METHODS AND MATERIALS: Three healthy volunteers underwent MR tagging studies
      after inhalation of 1 L HP (3)He gas diluted with nitrogen. Multiple-slice two
      dimensional and volumetric three-dimensional MR tagged images of the lungs were
      obtained at end-inhalation and end-exhalation, and displacement vector maps were
      computed. RESULTS: The grids of tag lines in the HP (3)He MR images were well
      defined at end-inhalation and remained evident at end-exhalation. Displacement
      vector maps clearly demonstrated the regional lung motion and deformation that
      occurred during exhalation. Discontinuity and differences in motion pattern
      between two adjacent lung lobes were readily resolved. CONCLUSIONS:
      Hyperpolarized helium-3 MR tagging technique can be used for direct in vivo
      measurement of respiratory lung motion on a regional basis. This technique may
      lend new insights into the regional pulmonary biomechanics and thus provide
      valuable information for the deformable registration of lung.

PMID- 17445998
TI  - Prognostic and predictive value of baseline and posttreatment molecular marker
      expression in locally advanced rectal cancer treated with neoadjuvant
      chemoradiotherapy.
AB  - PURPOSE: To evaluate expression of a panel of molecular markers, including p53,
      p21, MLH1, MSH2, MIB-1, thymidylate synthase, epidermal growth factor receptor
      (EGFR), and tissue vascular endothelial growth factor (VEGF), before and after
      treatment in patients treated with neoadjuvant chemoradiotherapy for locally
      advanced rectal cancer, to correlate the constitutive profile and dynamics of
      expression with pathologic response and outcome. METHODS AND MATERIALS:
      Expression of biomarkers was evaluated by immunohistochemistry in tumor samples
      from 91 patients with clinical Stage II and III rectal cancer treated with
      preoperative pelvic radiotherapy (50 Gy) plus concurrent 5-fluorouracil by
      continuous intravenous infusion. RESULTS: A pathologic complete remission was
      observed in 14 patients (15.4%). Patients with MLH1-positive tumors had a higher
      pathologic complete response rate (24.3% vs. 9.4%; p = 0.055). Low expression of
      constitutive p21, absence of EGFR expression after chemoradiotherapy, and high
      Dworak's tumor regression grade (TRG) were significantly associated with improved
      disease-free survival and overall survival. A high MIB-1 value after
      chemoradiotherapy was significantly associated with worse overall survival.
      Multivariate analysis confirmed the prognostic value of constitutive p21
      expression as well as EGFR expression and MIB-1 value after chemoradiotherapy
      among patients not achieving TRG 3-4. CONCLUSIONS: In our study, we observed the
      independent prognostic value of EGFR expression after chemoradiotherapy on
      disease-free survival. Moreover, our study suggests that a constitutive high p21
      expression and a high MIB-1 value after neoadjuvant chemoradiotherapy treatment
      could predict worse outcome in locally advanced rectal cancer.

PMID- 17445999
TI  - Nonrigid image registration for head and neck cancer radiotherapy treatment
      planning with PET/CT.
AB  - PURPOSE: Head and neck radiotherapy planning with positron emission
      tomography/computed tomography (PET/CT) requires the images to be reliably
      registered with treatment planning CT. Acquiring PET/CT in treatment position is
      problematic, and in practice for some patients it may be beneficial to use
      diagnostic PET/CT for radiotherapy planning. Therefore, the aim of this study was
      first to quantify the image registration accuracy of PET/CT to radiotherapy CT
      and, second, to assess whether PET/CT acquired in diagnostic position can be
      registered to planning CT. METHODS AND MATERIALS: Positron emission tomography/CT
      acquired in diagnostic and treatment position for five patients with head and
      neck cancer was registered to radiotherapy planning CT using both rigid and
      nonrigid image registration. The root mean squared error for each method was
      calculated from a set of anatomic landmarks marked by four independent observers.
      RESULTS: Nonrigid and rigid registration errors for treatment position PET/CT to
      planning CT were 2.77 +/- 0.80 mm and 4.96 +/- 2.38 mm, respectively, p = 0.001.
      Applying the nonrigid registration to diagnostic position PET/CT produced a more
      accurate match to the planning CT than rigid registration of treatment position
      PET/CT (3.20 +/- 1.22 mm and 4.96 +/- 2.38 mm, respectively, p = 0.012).
      CONCLUSIONS: Nonrigid registration provides a more accurate registration of head
      and neck PET/CT to treatment planning CT than rigid registration. In addition,
      nonrigid registration of PET/CT acquired with patients in a standardized,
      diagnostic position can provide images registered to planning CT with greater
      accuracy than a rigid registration of PET/CT images acquired in treatment
      position. This may allow greater flexibility in the timing of PET/CT for head and
      neck cancer patients due to undergo radiotherapy.

PMID- 17446000
TI  - Primary and central hypothyroidism after radiotherapy for head-and-neck tumors.
AB  - PURPOSE: To investigate the incidence of radiotherapy (RT)-induced central and
      primary hypothyroidism regarding total dose, fractionation, and adjuvant
      chemotherapy. METHODS AND MATERIALS: We retrospectively reviewed the data from
      312 patients treated with RT for extracranial head-and-neck tumors between 1964
      and 2000. The cervical lymph nodes were irradiated in 197 patients. The radiation
      doses to the thyroid gland and hypothalamic-pituitary axis were estimated by
      reconstructing the treatment plans. RESULTS: Clinical central hypothyroidism (CH)
      was observed in 17 patients (5.4%); the median clinical latency was 4.8 years.
      Clinical primary hypothyroidism (PH) was observed in 40 patients (20.3%); the
      median clinical latency was 3.1 years. Multivariate analysis of clinical CH
      revealed that fractionation, adjuvant chemotherapy, and total dose to the
      pituitary were not significant. Multivariate analysis of clinical PH revealed
      that the total dose to the thyroid (p = 0.043) was significant, but adjuvant
      chemotherapy, age, and gender were not. Of the patients tested for
      hypopituitarism, 14 (20.3%) of 69 demonstrated subclinical CH and 17 (27.4%) of
      62 demonstrated subclinical PH. The 5-year and 10-year rates of freedom from
      clinical CH and PH were 97% and 87% and 68% and 67%, respectively. Of the
      patients tested, the 5-year and 10-year rates of freedom from subclinical CH and
      PH were 91% and 78% and 71% and 71%, respectively. CONCLUSION: Clinical and
      subclinical manifestations of late radiation toxicity were observed in the
      thyroid and hypothalamic-pituitary axis. Although CH did not indicate a
      dependence on fractionation, adjuvant chemotherapy, or total dose to the
      pituitary, PH showed a dependence on the total dose to the thyroid gland.

PMID- 17446001
TI  - Preserving functional lung using perfusion imaging and intensity-modulated
      radiation therapy for advanced-stage non-small cell lung cancer.
AB  - PURPOSE: To assess quantitatively the impact of incorporating functional lung
      imaging into intensity-modulated radiation therapy planning for locally advanced
      non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Sixteen patients with
      advanced-stage NSCLC who underwent radiotherapy were included in this study.
      Before radiotherapy, each patient underwent lung perfusion imaging with single
      photon-emission computed tomography and X-ray computed tomography (SPECT-CT). The
      SPECT-CT was registered with simulation CT and was used to segment the 50- and 90
      percentile hyperperfusion lung (F50 lung and F90 lung). Two IMRT plans were
      designed and compared in each patient: an anatomic plan using simulation CT alone
      and a functional plan using SPECT-CT in addition to the simulation CT. Dosimetric
      parameters of the two types of plans were compared in terms of tumor coverage and
      avoidance of normal tissues. RESULTS: In incorporating perfusion information in
      IMRT planning, the median reductions in the mean doses to the F50 and F90 lung in
      the functional plan were 2.2 and 4.2 Gy, respectively, compared with those in the
      anatomic plans. The median reductions in the percentage of volume irradiated with
      >5 Gy, >10 Gy, and >20 Gy in the functional plans were 7.1%, 6.0%, and 5.1%,
      respectively, for F50 lung, and 11.7%, 12.0%, and 6.8%, respectively, for F90
      lung. A greater degree of sparing of the functional lung was achieved for
      patients with large perfusion defects compared with those with relatively uniform
      perfusion distribution. CONCLUSION: Function-guided IMRT planning appears to be
      effective in preserving functional lung in locally advanced-stage NSCLC patients.

PMID- 17446002
TI  - Treatment and prognosis of squamous cell carcinoma of the external auditory canal
      and middle ear: a multi-institutional retrospective review of 87 patients.
AB  - PURPOSE: To examine the relative roles of surgery, radiotherapy, and chemotherapy
      in the management of patients with squamous cell carcinomas of the external
      auditory canal and middle ear. METHODS AND MATERIALS: The records of 87 patients
      with histologically confirmed squamous cell carcinoma who were treated between
      1984 and 2005 were reviewed. Fifty-three patients (61%) were treated with surgery
      and radiotherapy (S + RT group) and the remaining 34 patients with radiotherapy
      alone (RT group). Chemotherapy was administered in 34 patients (39%). RESULTS:
      The 5-year actuarial overall and disease-free survival (DFS) rates for all
      patients were 55% and 54%, respectively. On univariate analysis, T stage (Stell's
      classification), treatment modality, and Karnofsky performance status had
      significant impact on DFS. On multivariate analysis, T stage and treatment
      modality were significant prognostic factors. Chemotherapy did not influence DFS.
      The 5-year DFS rate in T1, T2, and T3 patients was 83%, 45%, and 0 in the RT
      group (p < 0.0001) and 75%, 75%, and 46% in the S + RT group (p = 0.13),
      respectively. The 5-year DFS rate in patients with negative surgical margins,
      those with positive margins, and those with macroscopic residual disease was 83%,
      55%, and 38%, respectively (p = 0.007). CONCLUSIONS: Radical radiotherapy is the
      treatment of choice for early-stage (T1) diseases, whereas surgery (negative
      surgical margins if possible) with radiotherapy is recommended as the standard
      care for advanced (T2-3) disease. Further clarification on the role of
      chemotherapy is necessary.

PMID- 17446003
TI  - Single-fraction intraoperative radiotherapy for breast cancer: early cosmetic
      results.
AB  - PURPOSE: To evaluate the cosmetic outcome of patients treated with wide local
      excision and intraoperative radiotherapy for early-stage breast cancer. METHODS
      AND MATERIALS: A total of 50 women were treated on a pilot study to evaluate the
      feasibility of intraoperative radiotherapy at wide local excision. The
      eligibility criteria included age >60, tumor size </=2.0 cm, clinically negative
      lymph nodes, and biopsy-established diagnosis. After wide local excision, a
      custom breast applicator was placed in the excision cavity, and a dose of 20 Gy
      was prescribed to a depth of 1 cm. After 18 patients were treated, the dose was
      constrained laterally to 18 Gy. The cosmetic outcome was evaluated by photographs
      at baseline and at 6 and 12 months postoperatively. Four examiners graded the
      photographs for symmetry, edema, discoloration, contour, and scarring. The grades
      were evaluated in relationship to the volume of irradiated tissue, tumor
      location, and dose at the lateral aspects of the cavity. RESULTS: The median
      volume of tissue receiving 100% of the prescription dose was 47 cm(3) (range, 20
      97 cm(3)). Patients with </=47 cm(3) of treated tissue had better cosmetic
      outcomes than did the women who had >47 cm(3) of treated tissue. Women who had
      received 18 Gy at the lateral aspects of their cavities had better cosmetic
      outcomes than did women who had received 20 Gy at the lateral aspects. When
      comparing the 6- and 12-month results, the scores remained stable for 63%,
      improved for 17%, and worsened for 20%. CONCLUSION: Intraoperative radiotherapy
      appears feasible for selected patients. A favorable cosmetic outcome appears to
      be related to a smaller treatment volume. The cosmetic outcome is acceptable,
      although additional follow-up is necessary.

PMID- 17446004
TI  - Accuracy of life tables in predicting overall survival in candidates for
      radiotherapy for prostate cancer.
AB  - PURPOSE: To test the accuracy of life tables (LTs) in predicting survival in men
      treated with radiotherapy for localized prostate cancer. METHODS AND MATERIALS:
      We selected the records of 3,176 patients treated with radiotherapy and who had
      no clinical evidence of disease relapse. Life table-derived life expectancy (LE)
      was defined for every individual using a population-specific LT. Age, Charlson
      Comorbidity Index (CCI), and LT-derived LE were then used as predictors of
      overall mortality in Cox regression models. Predictive accuracy (PA) was
      estimated with the Harrell's concordance index and was internally validated with
      200 bootstrap resamples. RESULTS: The actuarial median survival was 4.7 years
      (mean, 6.4 years). At radiotherapy, median age was 70.6 years, median CCI was 2,
      and median LT-derived LE was 12 years. All variables were statistically
      significant predictors of overall mortality (all p values <0.001). Age (PA,
      60.2%), CCI (PA, 60.1%), and LT-derived LE (PA, 60.2%) were equally accurate.
      Finally, when age and CCI were combined (PA, 63.2%), both variables provided more
      accurate mortality predictions than either variable alone (all p values = 0.01).
      CONCLUSIONS: Life tables have a limited ability to predict LE in patients treated
      with radiotherapy for prostate cancer. We, therefore, recommend the use of
      multivariate prognostic models that integrate several variables, such as at least
      age and comorbidities, to estimate LE. This might help to improve LE estimation
      during prostate cancer treatment decision making.

PMID- 17446005
TI  - Distribution of brain metastases in relation to the hippocampus: implications for
      neurocognitive functional preservation.
AB  - PURPOSE: With the advent of intensity-modulated radiotherapy, the ability to
      limit the radiation dose to normal tissue offers an avenue to limit side effects.
      This study attempted to delineate the distribution of brain metastases with
      relation to the hippocampus for the purpose of exploring the viability of
      tomotherapy-guided hippocampal sparing therapy potentially to reduce
      neurocognitive deficits from radiation. METHODS AND MATERIALS: The pre
      radiotherapy T1-weighted, postcontrast axial MR images of 100 patients who
      received whole brain radiotherapy, stereotactic radiosurgery, or a radiosurgical
      boost following whole brain radiotherapy between 2002 and 2006 were examined. We
      contoured brain metastases as well as hippocampi with 5-, 10-, and 15-mm
      expansion envelopes. RESULTS: Of the 272 identified metastases, 3.3% (n = 9) were
      within 5 mm of the hippocampus, and 86.4% of metastases were greater than 15 mm
      from the hippocampus (n = 235). The most common location for metastatic disease
      was the frontal lobe (31.6%, n = 86). This was followed by the cerebellum (24.3%,
      n = 66), parietal lobe (16.9%, n = 46), temporal lobe (12.9%, n = 35), occipital
      lobe (7.7%, n = 21), deep brain nuclei (4.0%, n = 11), and brainstem (2.6%, n =
      7). CONCLUSIONS: Of the 100 patients, 8 had metastases within 5 mm of the
      hippocampus. Hence, a 5-mm margin around the hippocampus for conformal avoidance
      whole brain radiotherapy represents an acceptable risk, especially because these
      patients in the absence of any other intracranial disease could be salvaged using
      stereotactic radiosurgery. Moreover, we developed a hippocampal sparing
      tomotherapy plan as proof of principle to verify the feasibility of this therapy
      in the setting of brain metastases.

PMID- 17446006
TI  - [High-dose immunoglobulin during pregnancy for two patients with risk of
      recurrent neonatal haemochromatosis].
AB  - Two patients, with prior affected children with Neonatal Haemochromatosis [NH],
      benefited from intravenous immunoglobulin treatment during their following
      pregnancy in order to prevent recurrent NH. Whereas NH is a severe disease with
      high risk of recurrence and high mortality rate (about 80%), a recent treatment
      was suggested in the USA, which seems to completely modify the prognosis of this
      pathology. We proposed this treatment for two patients with indeed apparent
      benefit, giving birth to two healthy babies.

PMID- 17446008
TI  - [Pulmonary edema during calcium-channel blockers therapy: role of predisposing or
      pharmacologic factors?].
AB  - Calcium channel blockers of the dihydropyridin's family have been associated with
      the onset of an acute pulmonary edema when they are used as a treatment of
      preterm labor. We report here four cases of pulmonary edema in pregnant women
      treated with nicardipine (Loxen) for preterm labor. The physiopathology of
      pulmonary edema, the pharmacology of calcium channel blockers of dihydropyridin's
      family and the detailed analysis of our cases and those of the literature make us
      discuss of the role of these agents and associated population and risk factors in
      such complication.

PMID- 17446007
TI  - [Pregnant woman and road safety: a numerical approach. Application to a
      restrained third trimester pregnant woman in frontal impact].
AB  - OBJECTIVES: The goal of our work is the development of a numerical model of
      pregnant woman in driving position. We present an application to the study of
      injury mechanisms during a frontal car crash for a seat belt restrained pregnant
      woman in driving position. MATERIALS AND METHODS: We integrated a digital
      representation of a pregnant uterus, foetus and placenta in a previous existing
      numerical model of non pregnant Human body in driving position, the Humos model.
      The realization of a numerical simulation of a frontal car crash enabled us to
      analyze the part played by the safety belt in the organic traumatisms. RESULTS:
      Three phases were highlighted. The first phase consists of a translation forwards
      of the pregnant uterus during the impact. The second phase is a rotation forwards
      in the sagittal plan of the pregnant uterus with for axis of rotation the
      posterior wall of the pubis. The third phase is a vertical adjustment coupled to
      a translation of the uterus towards the back. This translation leads the uterus
      to impact the spine. CONCLUSION: The development of a pregnant numerical model in
      the field of accidentology allows the analysis of organic traumatisms. That makes
      it possible to study the role played by the existing safety systems. This model
      might make it possible to develop safety systems specific to the pregnant woman.

PMID- 17446009
TI  - [Maternal nutrition as a determinant of fetal weight: role of trace elements and
      vitamins].
AB  - OBJECTIVE: To evaluate maternal trace elements and vitamins food intake in the
      last month of pregnancy and assess their effect on fetal weight. MATERIAL AND
      METHODS: It is a food intake survey led near 350 pregnant women. All women
      participated in a nutritional survey and were at term. To examine dietary
      intakes, food frequency questionnaires were completed before delivery on the diet
      during the last 24 hours. Authors compared the maternal intakes to the
      recommended allowance and analyzed the correlation between these intakes and
      fetal weight. RESULTS: This study confirmed the influence of factors such as
      parity, maternal BMI and term of pregnancy on the fetal weight. The mean daily
      intakes of iron (10.7 mg/day), calcium (553 mg/day), zinc (6.2 mg/day), magnesium
      (284.3 mg/day) were lower than recommended. The mean daily intakes of vitamins C
      and E did not differ from recommended allowance. Only calcium intakes were
      significantly correlated to birth weight. CONCLUSION: We noted a deficiency of
      most of these intakes compared to the recommended dietary allowance. Trace
      elements and vitamins C, E maternal-food intakes in the end of pregnancy don't
      seem to be a significant determinant of foetal weight.

PMID- 17446010
TI  - Biochemotherapy with standard chemotherapies plus the pineal hormone melatonin in
      the treatment of advanced solid neoplasms.
AB  - It is known since many years that the pineal hormone melatonin (MLT) may play
      anticancer activity through several mechanisms, including antiproliferative and
      immunostimulating effects. Moreover, it exerts an important antioxidant action.
      Therefore, MLT could be useful in the treatment of human neoplasms, either alone
      or in association with chemotherapy. The present study was performed to evaluate
      the influence of a concomitant MLT administration on efficacy and toxicity of
      several chemotherapeutic combinations in metastatic solid tumor patients,
      suffering from non-small cell lung cancer (NSCLC) or gastrointestinal tumors. The
      study included 370 patients who were randomized to receive chemotherapy alone or
      chemotherapy plus MLT (20 mg/day orally in the evening every day). NSCLC patients
      received cisplatin (CDDP) plus etoposide or CDDP plus gemcitabine. Colorectal
      cancer patients were treated with oxaliplatin plus 5-fluorouracil (5-FU), or
      weekly CPT-11 or 5-FU and folates (FA). Finally, gastric cancer patients received
      CDDP, epirubicin, 5-FU and FA or weekly 5-FU plus FA. The overall tumor
      regression rate achieved in patients concomitantly treated with MLT was
      significantly higher than that found in those treated with chemotherapy alone.
      Moreover, the 2-year survival rate was significantly higher in patients
      concomitantly treated with MLT. These results confirm in human the anticancer
      therapeutic properties of the pineal hormone MLT, which may enhance the efficacy
      of the standard anticancer chemotherapies.

PMID- 17446011
TI  - Within-session patterns in variable-interval schedule performance: Variation with
      deprivation level.
AB  - Previous research has shown that patterns in operant responding may change within
      the course of individual experimental sessions. The proper interpretation of such
      changes is controversial. At least one source of this controversy may lie in
      unstated experimental practices across laboratories, as published reports often
      have failed to detail important particulars of deprivation operations. The
      present study was aimed at gathering descriptive data on the contribution of
      deprivation operations to the observation of within-session changes. In two
      experiments, four food deprived pigeons were exposed to a multiple variable
      interval 30-s variable-interval 30-s schedule of grain presentation, wherein each
      grain presentation was kept constant at 5s. In Condition I, a session-entry
      criterion was in place that permitted the pigeon access to the daily session only
      if its body weight fell within controlled limits. Within-session rates of
      responding were generally stable. In Condition II, the entry criterion was
      removed and experimental sessions were conducted 6 days per week. The effect of
      removing the session-entry criterion was to increase body weight for all birds
      and decrease food intake across conditions. With no session entry criterion,
      robust within-session changes were observed for three of the four pigeons. The
      results suggest that rich schedules of reinforcement often used in the analysis
      of within-session changes can produce substantial reductions in deprivation
      levels that require up to several days to reverse. Future experiments in this
      area should take precautions to insure that deprivation is tightly controlled and
      report such measures to eliminate potential errors in replication.

PMID- 17446012
TI  - Applications of timing theories to a peak procedure.
AB  - This article describes applications of scalar expectancy theory (SET), learning
      to-time theory (LeT), and Packet theory to data from a peak procedure. Twelve
      rats were trained in a multiple cued-interval procedure with two fixed intervals
      (60 and 120 s) signaled by houselight and white noise. Twenty-five percent of the
      cycles were nonfood cycles, which were 360 s long and had no reinforcement. Mean
      and individual response rates on nonfood cycles were fitted with explicit
      solutions of SET, LeT and Packet theory. Applications of the three timing
      theories were compared in terms of goodness of fit and complexity.

PMID- 17446013
TI  - Concurrent and simultaneous drug and alcohol use: results of the 2000 National
      Alcohol Survey.
AB  - This study estimates the prevalence, assesses predictors and evaluates factors
      associated with concurrent and simultaneous use of drugs and alcohol in the
      United States population. Using data from the 2000 National Alcohol Survey
      (n=7612), respondents were asked if they used specific drugs in the last 12
      months. Current drinkers who reported using each type of drug were asked if they
      used alcohol and the drug at the same time. Approximately 10% reported using
      marijuana in the last 12 months (concurrent use); 7% reported drinking alcohol
      and using marijuana at the same time (simultaneous use). Approximately 5% of
      current drinkers reported using drugs other than marijuana in the last 12 months;
      1.7% reported drinking alcohol and using drugs other than marijuana at the same
      time. Being younger, having less than a high school education, not having a
      regular partner and having heavier drinking patterns were associated with using
      alcohol and marijuana simultaneously. Simultaneous use of marijuana and alcohol
      as well as other drugs and alcohol were significantly related to social
      consequences, alcohol dependence, and depression. These results mirror clinical
      populations in which increasingly younger clients report use of alcohol and drugs
      and need treatment for both.

PMID- 17446014
TI  - The Women's Recovery Group Study: a Stage I trial of women-focused group therapy
      for substance use disorders versus mixed-gender group drug counseling.
AB  - The aim of this Stage I Behavioral Development Trial was to develop a manual
      based 12-session Women's Recovery Group (WRG) and to pilot test this new
      treatment in a randomized controlled trial against a mixed-gender Group Drug
      Counseling (GDC), an effective manual-based treatment for substance use
      disorders. After initial manual development, two pre-pilot groups of WRG were
      conducted to determine feasibility and initial acceptability of the treatment
      among subjects and therapists. In the pilot stage, women were randomized to
      either WRG or GDC. No significant differences in substance use outcomes were
      found between WRG and GDC during the 12-week group treatment. However, during the
      6-month post-treatment follow-up, WRG members demonstrated a pattern of continued
      reductions in substance use while GDC women did not. In addition, pilot WRG women
      with alcohol dependence had significantly greater reductions in average
      drinks/drinking day than GDC women 6 months post-treatment (p<.03, effect
      size=0.81). While satisfaction with both groups was high, women were
      significantly more satisfied with WRG than GDC (p<.009, effect size=1.11). In
      this study, the newly developed 12-session women-focused WRG was feasible with
      high satisfaction among participants. It was equally effective as mixed-gender
      GDC in reducing substance use during the 12-week in-treatment phase, but
      demonstrated significantly greater improvement in reductions in drug and alcohol
      use over the post-treatment follow-up phase compared with GDC. A women-focused
      single-gender group treatment may enhance longer-term clinical outcomes among
      women with substance use disorders.

PMID- 17446015
TI  - Cationic transfersomes based topical genetic vaccine against hepatitis B.
AB  - DNA vaccines have been shown to elicit both cellular and humoral immune responses
      and to be effective in a variety of preclinical bacterial, viral, and parasitic
      animal models. We have recently described a needle-free method of vaccination,
      transcutaneous immunization, based on topical application of vaccine antigens on
      intact skin using a novel carrier system, namely transfersomes. In the present
      study, a novel modified version of transfersomes, i.e., cationic transfersomes
      for topical DNA vaccine delivery has been developed. Cationic transfersomes
      composed of cationic lipid DOTMA and sodium deoxycholate as constitutive lipids
      were prepared and optimized for their size, shape, zeta potentials, deformability
      and loading efficiency. Plasmid DNA encoding hepatitis B surface antigen (HBsAg)
      was loaded in the cationic transfersomes using charge neutralization method. The
      immune stimulating activity was studied by measuring serum anti-HBsAg titer and
      cytokines level (IL-2 and IFN-gamma) following topical applications of plasmid
      DNA loaded cationic transfersomes in Balb/c mice and results were compared with
      naked DNA applied topically as well as naked DNA and pure recombinant HBsAg
      administered intramuscularly. Results revealed that DNA loaded cationic
      transfersomes elicited significantly (*P<0.05) higher anti-HBsAg antibody titer
      and cytokines level as compared to naked DNA. It was also observed that topical
      application of DNA loaded cationic transfersomes elicited a comparable serum
      antibody titer and endogenous cytokines levels as produced after intramuscular
      recombinant HBsAg administration. The study signifies the potential of cationic
      transfersomes as DNA vaccine carriers for effective topical immunization.

PMID- 17446017
TI  - Predictive stress tests to study the influence of processing procedures on long
      term stability of supersaturated pharmaceutical o/w creams.
AB  - Partial coalescence in emulsions is a destabilization mechanism whereby the
      droplets retain their individual identity but there is a molecular contact
      between their content. This process can occur under fluctuating temperatures
      and/or shear stress, which effects the stability and quality of emulsions. In the
      case of topical drug delivery systems, in particular supersaturated oil-in-water
      (o/w) creams, the molecular exchange of dissolved drug from one droplet to the
      other is a critical issue because it can induce drug crystallization and enhance
      crystal growth. In this work two approaches to address the problem are reported:
      the stability of the emulsion in relation to (i) shear exposure and (ii)
      temperature cycling. Some ideas on how this approach can be used to identify
      critical process parameters and predict long term stability of supersaturated
      emulsions are discussed.

PMID- 17446016
TI  - Effect of injection routes on pharmacokinetics and lactone/carboxylate
      equilibrium of 9-Nitrocamptothecin in rats.
AB  - Pharmacokinetics and lactone/carboxylate equilibrium of 9-Nitrocamptothecin (9
      NC) were compared after intravenous (i.v.) and intramuscular (i.m.) injection at
      a dose of 1.5mg/kg 9-NC solution. The concentrations of three different forms of
      9-NC, namely lactone, carboxylate and total 9-NC, were measured by HPLC analysis.
      Injection routes were demonstrated to have significant effect on pharmacokinetics
      of 9-NC. Compared with i.v. injection route, mean residence time (MRT) of 9-NC
      three forms was significantly prolonged following i.m. route (p<0.05). The AUC(0
      infinity) ratios of i.m. to i.v. route were calculated to be 102+/-43%, 273+/
      221% and 150+/-62% for lactone, carboxylate and total 9-NC, respectively.
      Compared with i.v. injection route, although AUC(0-infinity) was barely changed,
      MRT of lactone 9-NC was dramatically prolonged 4.5-fold after i.m. injection,
      which may account for the reported improved antitumor efficacy. However, the
      results of the present study also demonstrated that i.m. injection route
      increased both AUC(0-infinity) and MRT of carboxylate 9-NC more significantly.
      Since the carboxylate form of CPT analogs including 9-NC is associated with their
      unwanted toxicity, i.m. injection route might lead to severe toxicity compared
      with i.v. route. Lactone/carboxylate equilibrium was also significantly
      influenced by injection routes. Based on the AUC(0-infinity) measurements, the
      lactone 9-NC constituted 50+/-8% and 32+/-7% of circulating total 9-NC after i.v.
      or i.m. administration, respectively (p<0.01).

PMID- 17446018
TI  - Wen-pi-tang-Hab-Wu-ling-san attenuates kidney ischemia/reperfusion injury in
      mice. A role for antioxidant enzymes and heat-shock proteins.
AB  - The purpose of this study was to investigate the effects of Wen-pi-tang-Hab-Wu
      ling-san (WHW) extract, which has been used for treatment of renal diseases, on
      kidney ischemia/reperfusion (I/R) injury. Thirty minutes of bilateral renal
      ischemia resulted in disruption of kidney tubular epithelial cells and increased
      plasma creatinine levels in mice, however these effects were significantly
      attenuated when WHW was administered prior to I/R. WHW-administration also
      inhibited post-ischemic decreases of catalase, copper-zinc superoxide dismutase
      (CuZnSOD), and manganese superoxide dismutase (MnSOD) activity in kidney tissue,
      leading to decreased tissue hydrogen peroxide levels and lipid peroxidation. Post
      ischemic increases of heat-shock protein (HSP)-27 and -72 expressions were
      greater in mouse kidneys that received WHW. In conclusion, WHW-administration
      reduced kidney susceptibility to I/R injury, and this reduced susceptibility was
      associated with greater post-ischemic activation of catalase, CuZnSOD and MnSOD,
      resulting in reduced hydrogen peroxide levels and lipid peroxidation, as well as
      higher post-ischemic expression of HSP-27 and -72.

PMID- 17446019
TI  - Chemical composition and anti-inflammatory activity of copaiba oils from
      Copaifera cearensis Huber ex Ducke, Copaifera reticulata Ducke and Copaifera
      multijuga Hayne--a comparative study.
AB  - Copaiba oil is an oleoresin obtained from the Copaifera L. genus (Leguminoseae)
      commonly featured in anti-inflammatory recipe prescribed by Amazonian traditional
      medical practitioners and featured in Europe and North America pharmacopeias of
      the past. Chemical and anti-inflammatory activity investigations from the copaiba
      oils obtained from Copaifera multijuga Hayne, Copaifera cearensis Huber ex Ducke
      and Copaifera reticulata Ducke species have proved that, although similar, these
      oleoresins possess varied composition and anti-inflammatory activity.
      Chromatographic studies showed that the main compound among sesquiterpenes was
      beta-caryophyllene (57.5, 19.7 and 40.9%, respectively), followed by alpha
      humulene, alpha-copaene, alpha-bergamotene, delta-cadinene, with different
      amounts in each oleoresin. Among the diterpenes, copalic acid was the main
      component from Copaifera multijuga Hayne (6.2%) and was found in all the
      oleoresins studied. In Copaifera cearensis Huber ex Ducke, clorechinic (11.3%)
      and hardwickiic acids (6.2%) were the major diterpenes while kaurenoic (3.9%) and
      kolavenic acids (3.4%) predominated in Copaifera reticulata Ducke. The
      pharmacologic effects of the three oleoresins were evaluated in vitro by
      measuring the NO production by murine macrophages and in vivo using the zymosan
      induced pleurisy model in mice. The Copaiba Oil from Copaifera multijuga Hayne
      (100 mg/kg) was the most potent, inhibiting both NO production and the pleurisy
      induced by zymosan. The oleoresins from Copaifera cearensis Huber ex Ducke and
      Copaifera reticulata Ducke were also able to inhibit NO production and the
      pleurisy but with less intensity.

PMID- 17446020
TI  - Evaluation of contraceptive activity of methanol extract of Dendrophthoe falcata
      stem in male albino rats.
AB  - The present study was undertaken to evaluate the contraceptive efficacy of
      methanol extract of Dendrophthoe falcata Ettingsh (family-Loranthaceae), stem in
      male albino rats as reported in folk remedies. Adult proven fertile male rats
      were gavaged methanol extract of D. falcata stem at 50, 100 and 200mg/rat/day for
      60 days. The activity was compared with standard drug, i.e. Lonidamine. On day 61
      the animals were autopsied and the testes, epididymides, seminal vesicle and
      ventral prostate were dissected out and weighed. Sperm motility and density and
      serum testosterone level were assessed. The sperm motility and density were
      significantly reduced. The histoarchitecture of testes revealed degenerative
      changes in the seminiferous tubules, arrest of spermatogenesis at the stage of
      round spermatid. Serum testosterone levels were decreased significantly in all
      treatment groups. It is concluded that D. falcata methanol stem extract showed a
      significant effect on fertility in male rats as reported in folk remedies.

PMID- 17446022
TI  - [The public health landscape in France is evolving].

PMID- 17446023
TI  - [A strategy for therapy of depressive disorders and anxiety disorders by a health
      education intervention in medical consultations: the results of the APRAND
      program].
AB  - BACKGROUND: Studies devoted to the detection and treatment of anxiety and
      depression in adult populations show that at least 10% meet ICD10 criteria for an
      anxiety or a depressive disorder, but only half are diagnosed as such and only
      one third of those receive appropriate treatment. The goal of the APRAND program
      was to explore the possibility of improving management strategies via health
      education during doctors' visits. METHODS: In 2001, EDF-GDF conducted an
      experimental program in which 21 physicians from its in-house health insurance
      program used the MINI mental state examination to screen for ICD10 criteria for
      anxiety and depressive disorders in 9743 employees on sick leave. A "here
      elsewhere" epidemiologic study evaluated the program, recording the initial
      diagnoses and studying a year later the outcome of the persons identified with
      these disorders in 8 active centers (with prevention activities) and in 13
      control centers (without prevention activities). The activities consisted of
      explanations of the disorders identified, delivery of the test results, delivery
      of leaflets based on the WHO guidelines, and strong recommendations to see a
      general practitioner, or a psychiatrist, or the occupational physician, if
      necessary. Logistic regressions compared the two groups, taking into account sex,
      age, geographic region, comorbidity, and medical care at screening. RESULTS:
      Preventive activities were significantly associated with the disappearance at 1
      year of depressive episodes (OR=1.93; CI 95%; 1.3-2.84) and of phobic or panic
      disorders (OR=1.98; CI 95%; 1.14-3.44). The only other variables affecting
      prognosis were age and sex. The probability of recovery or remission increased by
      10 to 20% at active centers, according to age, sex and disorder. Moreover, the
      physicians reported that they learned a great deal from the program, which thus
      also improved their practices. CONCLUSION: Diagnosis and prognosis of depressive
      episodes and phobic and panic disorders in adult populations can be improved by a
      preventive diagnostic and educational approach of the type used by APRAND during
      doctor's visits.

PMID- 17446024
TI  - The medical consequences of narghile (hookah, shisha) use in the world.
AB  - BACKGROUND: Hookah (narghile, shisha) smoking is growing worldwide and
      particularly in France. The main reasons for this are: first, the arrival on the
      market of new highly flavored tobacco-based mixtures; second, a new type of
      charcoal used as a quick heating source; third, the pleasure to experiment with
      an exotic orientalist practice or the desire to return to the corresponding
      tradition; fourth, the belief that water filtration would lower the risk of
      smoking. METHODS AND RESULTS: Long-term epidemiological data on complications are
      scarce. Little is known about qualitative and quantitative transformations
      occurring when hookah is smoked (in particular regarding carcinogenic agents).
      Such information will be difficult to collect due to the lack of standardization
      for this mode of tobacco use. The only current consensus on this issue is that a
      significant amount of carbon monoxide is produced by the charcoal used to heat
      and distil the tobacco-molasses mixture. Apart from direct inhalation,
      concentrations measured in some fashionable hookah lounges and bars are
      particularly high. Moreover, the additives contained in the widely used quick
      lighting charcoals and their harmlessness remain unknown. CONCLUSION: This study
      sets out the available scientific knowledge regarding the real medical
      consequences related to the growing use of hookah and focuses on the best known
      and urgent issue, i.e. concern related to carbon monoxide intoxication in a very
      peculiar context.

PMID- 17446025
TI  - [Influence of surveillance period length on the incidence of methicillin
      resistant Staphylococcus aureus].

PMID- 17446026
TI  - [Campylobacter fetus bacteremia and cellulitis complicating a venous access port
      infection in an HIV infected patient].
AB  - Campylobacter fetus subspecies fetus is an opportunist Gram-negative bacillus,
      which is known to be a cause of systemic infections, mainly in immunocompromised
      patients. We report a C. fetus bacteremia and cellulitis complicating a venous
      access port infection in a patient with acquired immunodeficiency syndrome
      (AIDS). This bacillus seems to have a predilection for the vascular endothelium
      and its isolation is difficult. Physicians should be aware of C. fetus infection
      in patients with vascular devices. Microbiologists should accurately isolate this
      organism from clinical specimens by modifying incubation techniques and
      performing molecular biology. The prognosis seems to be improved by a prolonged
      betalactam antibiotic regimen, especially amoxicilline plus clavulanic acid. In
      HIV infected patients, quinolones that were successful in our case, should be
      used with caution because of increasing resistance to antibiotics.

PMID- 17446027
TI  - Extended longevity of queen honey bees compared to workers is associated with
      peroxidation-resistant membranes.
AB  - In the honey bee (Apis mellifera), depending on what they are fed, female eggs
      become either workers or queens. Although queens and workers share a common
      genome, the maximum lifespan of queens is an order-of-magnitude longer than
      workers. The mechanistic basis of this longevity difference is unknown. In order
      to test if differences in membrane composition could be involved we have compared
      the fatty acid composition of phospholipids of queen and worker honey bees. The
      cell membranes of both young and old honey bee queens are highly monounsaturated
      with very low content of polyunsaturates. Newly emerged workers have a similar
      membrane fatty acid composition to queens but within the first week of hive life,
      they increase the polyunsaturate content and decrease the monounsaturate content
      of their membranes, probably as a result of pollen consumption. This means their
      membranes likely become more susceptible to lipid peroxidation in this first week
      of hive life. The results support the suggestion that membrane composition might
      be an important factor in the determination of maximum lifespan. Assuming the
      same slope of the relationship between membrane peroxidation index and maximum
      lifespan as previously observed for mammal and bird species, we propose that the
      3-fold difference in peroxidation index of phospholipids of queens and workers is
      large enough to account for the order-of-magnitude difference in their longevity.

PMID- 17446028
TI  - Imaging treatment effects in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the commonest form of degenerative dementia and is
      characterised by progressive cognitive decline. Despite extensive research, the
      cause of AD is unknown and there is no cure at present. Of the deficits found in
      AD, that affecting the cholinergic neurotransmitter system is the best
      established and the only one translated into symptomatic treatment. Cholinergic
      enhancement with cholinesterase inhibitor (ChEI) drugs has been achieved and
      their efficacy and safety ascertained by conventional clinical trials. The
      mechanism of action of these drugs, however, is not well understood. Imaging with
      SPECT, PET, MRI and fMRI after treatment has clarified what happens in the brains
      of those AD patients treated with ChEI drugs. Studies with these techniques have
      identified increases in brain blood flow and glucose metabolism, restoration of
      nicotinic receptor function and re-establishment of task-related regional brain
      activation in response to cognitive stimulation after treatment. Structural MRI
      studies have explained, to some degree, why only a proportion of patients
      benefits from ChEI treatment and there is some evidence that some ChEI drugs
      might be neuroprotective. There are, however, many unsolved problems. Timing of
      treatment intervention to obtain maximum response and the determinants of
      treatment response are mostly unknown. It is also unclear whether administration
      of treatment in those patients who have no potential for response accelerates
      disease progression. These issues cannot be solved by conventional clinical
      trials. Pharmacoimaging studies could assist the development and refinement of
      drugs to treat those diseases, such as AD, which affect the central nervous
      system.

PMID- 17446029
TI  - Optimized conditions for the extraction of secondary volatile metabolites in
      Angelica roots by accelerated solvent extraction.
AB  - Accelerated solvent extraction (ASE) of three common Angelica species found in
      Asia: Angelica sinensis (Oliv.) Diels from China, Angelica acutiloba (Sieb. et
      Zucc.) Kitagawa from Japan, and Angelica gigas Nakai from Korea was investigated.
      Preliminary experiments, including the selection of the solvent, extraction time,
      pressure, static cycle and time were investigated to optimize experimental
      parameters. Kovats indices and mass spectra were used to identify the components
      in the various fractions. These were then confirmed using gas chromatography-mass
      spectrometry (GC-MS). A total of 18 compounds were identified, with qualitative
      differences and similarities observed among the cultivars. From the 18 compounds
      found in the ASE extract of danggui cultivars, the major components were
      decursin, decursinol angelate (A. gigas); butylidene dihydrophthalide, 4-hydroxy
      4-methyl-2-pentanone (A. sinensis); and 9,12-octadecanoic acid in Angelica
      acutiloba. The optimum ASE operating conditions were n-hexane as extraction
      solvent, extraction temperature and pressure of 80 degrees C and 1500 atm,
      respectively, static cycle of 2 min, and static time of 10 min. Under these
      conditions, the percentages of main analytes were increased.

PMID- 17446030
TI  - Simultaneous determination of seven major diterpenoids in Pseudolarix kaempferi
      by high-performance liquid chromatography DAD method.
AB  - A reversed phase high-performance liquid chromatography method was established
      for the first time to simultaneously qualify the seven major diterpenoids in
      Pseudolarix kaempferi, namely pseudolaric acid B O-beta-D-glucopyranoside (1),
      pseudolaric acid C2 (2), pseudolaric acid C1 (3), deacetylpseudolaric acid A (4),
      pseudolaric acid A O-beta-D-glucopyranoside (5), pseudolaric acid B (6) and
      pseudolaric acid A (7). The optimal conditions of separation and detection were
      achieved on an Inertsil ODS-3 column with gradient elution of methanol and 0.5%
      aqueous acetic acid (v/v) at the flow rate of 0.6 ml min(-1) within 40 min and
      detection wavelength set at 262 nm. All calibration curves showed good linear
      regression (r2>0.9999) within test ranges. This method provided good accuracy
      with recoveries in the range of 94.3-106.1% and good precision with R.S.D.s of
      repeatability and intermediate precision less than 0.57% and 4.67%, respectively.
      The method was successfully applied to qualitative and quantitative determination
      of 20 P. kaempferi among the 54 samples collected from different areas. The
      results revealed that the commercial crude drugs were seriously confused and the
      developed HPLC assay could be used as a suitable qualitative and quantitative
      determination method for P. kaempferi.

PMID- 17446031
TI  - Generic ciprofloxacin tablets contain the stated amount of drug and different
      impurity profiles: A 19F, 1H and DOSY NMR analysis.
AB  - The objective of this study was to control the purity of 16 commercial
      formulations of ciprofloxacin tablets purchased in different countries or via the
      Internet using 19F and 1H nuclear magnetic resonance (NMR). Twelve out of the
      sixteen commercial formulations of ciprofloxacin measured by 19F NMR contain the
      active ingredient within 100+/-5% of stated concentration. Three formulations
      have a lower ciprofloxacin content between 90 and 95% and one shows a higher
      concentration superior to 105%. The impurity profile was characterised using 19F
      and 1H NMR, and is characteristic of the manufacturer. Four to twelve fluorinated
      impurities among them fluoride ion and two already known compounds were detected
      and quantified in the sixteen formulations analysed by 19F NMR. Two other non
      fluorinated impurities were observed in the seven formulations analysed with 1H
      NMR. The total content of impurities as well as their individual levels are in
      agreement with those reported previously in the few studies devoted to
      ciprofloxacin purity. However, all the formulations do not comply with the limits
      for impurities given in the ciprofloxacin monograph of the European Pharmacopeia.
      Finally, a "signature" of the formulations was obtained with Diffusion-Ordered
      SpectroscopY (DOSY) 1H NMR which allowed the characterisation of some excipients
      present in the formulations studied.

PMID- 17446032
TI  - [Psoas compartment block with general anaesthesia: descriptive study of 93
      cases].
AB  - OBJECTIVES: During many years the approach to the lumbar plexus has been the
      anterior paravascular technique described as a "3-1" block by Winnie. The
      posterior approach results in a complete block of the principal nerves of the
      lumbar plexus. The goal of the study was to evaluate the performance of the psoas
      compartment block with general anaesthesia. STUDY DESIGN: Prospective,
      descriptive, non randomized study. PATIENTS AND METHODS: Ninety-three patients
      scheduled for hip surgery were studied after informed consent. Demographic data,
      technical aspects of the puncture, complications, and intra- and postoperative
      analgesics were recorded. RESULTS: The block was performed by resident alone,
      senior alone, both in respectively 44%, 45, and 11% of cases. The mean duration
      of the procedure was 6+/-3 min for the residents, 5+/-2 min for the seniors, and
      9+/-4 min for both. The transverse process was reach in 72% of cases during the
      first approach, after reorientation of the needle in the others cases, except 3
      failures of attempt. The lumbar plexus was assessed within 60-90 mm of depth,
      with a median of 75 mm. The motor response was mainly a femoral response; the
      minimal intensity of stimulation was ranged between 0.3 and 1 mA, with a median
      of 0.6 mA. The duration of analgesic block was 16.5+/-4.5 hours, with a median of
      18 hours. The morphine use during the first postoperative 24 hours was 8+/-8 mg,
      with a median of 5.6 mg. No neurologic complication was recorded at discharge
      from the hospital. CONCLUSION: The psoas compartment block with general
      anaesthesia have shown it feasibility and efficiency on intra- and postoperative
      analgesia during hip surgery.

PMID- 17446033
TI  - [Tracheal rupture after orotracheal intubation in intensive care].
AB  - We report a case of an iatrogenic tracheal rupture following an endotracheal
      intubation. The 78-year-old patient was admitted to the intensive care unit
      because of an acute respiratory failure related to a severe nosocomial pneumonia
      occurring 21 days after an abdominal aorta surgery. His main antecedent was a
      cigarette smoke-induced chronic obstructive pulmonary disease. Immediately after
      being intubated, a traumatic tracheobronchial rupture was suspected because of
      the sudden appearance of cervicothoracic subcutaneous emphysema. A thoracic
      computed tomography with multiplanar reformations confirmed the diagnosis and the
      evolution was unfortunately rapidly unfavourable. Risk factors, clinical and
      radiological aspects, and management of this rare but serious complication of
      endotracheal intubation will be discussed.

PMID- 17446034
TI  - Implementation of a weaning algorithm in postoperative cardiac ICU: simple enough
      to be implemented in a ventilator software.
AB  - OBJECTIVE: The aim of this study was to test the efficacy of a respiratory
      weaning algorithm (WA) in postoperative cardiac surgery patients. This algorithm
      was made simple enough to be implemented in medium-end ventilator software.
      PATIENTS: Twenty consecutive postoperative patients who underwent scheduled
      cardiac surgery with normal postoperative haemodynamic and respiratory status.
      METHODS: A 3 step WA (Controlled Mode Ventilation, Pressure Support (PS) at +20
      cmH2O and at +10 cmH2O) was applied every 15 minute by the same investigator. A
      15 minute period of respiratory stability at one step led to commute to a step
      ahead until patient was judged "ready for extubation" (RFE, i.e. stable during 15
      min under PS +10 cmH2O). Once reaching this time, the patient was left under PS
      +10 until nurse and doctors in charge decided extubation according to our routine
      clinical criteria. RESULTS: the patients were routinely extubated, in average
      187+/-169 min later than when judged RFE by the algorithm. Heart rate (P<0.05)
      and mean arterial pressure rose when they reached the time of effective
      extubation, by comparison to the RFE time point. CONCLUSION: A WA has clinical
      advantage in cardiac surgery as it reduces respiratory weaning duration. It helps
      to avoiding haemodynamic stress related to delayed extubation. Such an algorithm
      is simple enough to be implemented in medium-end ventilators.

PMID- 17446035
TI  - [Arrhythmias in sleep apnea syndrome].
AB  - Arrhythmias are more frequent in patients with sleep apnea syndrome. Bradycardias
      predominate. In the absence of controlled studies, it is difficult to link
      arrhythmias to sleep apnea syndrome or to the disease accompanying it (coronary
      disease, hypertension, etc.). Continuous positive airway pressure (CPAP) reduces
      arrhythmias significantly.

PMID- 17446036
TI  - [Combined pulmonary fibrosis and emphysema].
AB  - A syndrome including upper-lobe emphysema and pulmonary fibrosis of the lower
      lungs was recently characterized. It is found most often in men who are smokers
      or ex-smokers of more than 40 pack-years; their mean age is 65 years. Exertional
      dyspnea is always present. There are basal crackles. The disease has no known
      cause; the only certain risk factor is smoking. Pulmonary function tests show
      respiratory volumes and flows that are often normal or subnormal, while carbon
      monoxide transfer is substantially reduced and exercise hypoxemia is present.
      Diagnosis is based on findings from millimeter-slices of computed tomography of
      the chest, which show either centrilobular emphysema or upper-zone bullous
      emphysema, associated in 90% of cases with very suggestive paraseptal emphysema
      and diffuse infiltrating fibrosing lung disease at the bases (subpleural
      reticular opacities, honeycomb images, traction bronchiectasis), with more
      frequent ground glass opacities than in idiopathic pulmonary fibrosis. Pulmonary
      hypertension is present in almost half of all patients and represents the
      principal negative prognostic factor for this condition, which has a median
      survival of 6 years.

PMID- 17446037
TI  - [L-thyroxine pseudomalabsorption: a factitious disease].
AB  - INTRODUCTION: Thyroxine supplementation of patients with hypothyroidism is
      usually simple. A few patients, however, continue to present elevated TSH levels
      despite large doses of L-thyroxine. CASE: We report the case of a 71-year-old
      women who had had a thyroidectomy 10 years earlier and had since been
      hospitalized repeatedly for profound hypothyroidism. Despite her consistent
      claims of good adherence to her treatment regimen, we considered the diagnosis of
      L-thyroxine pseudomalabsorption and confirmed it by thyroid hormone absorption
      tests. DISCUSSION: L-thyroxine pseudomalabsorption due to concealed poor
      treatment adherence should be considered after ruling out drug or dietary
      interference and true organic malabsorption. Diagnosis of this factitious disease
      can be confirmed by L-thyroxine absorption tests.

PMID- 17446038
TI  - [Brugada syndrome].
AB  - Brugada syndrome is characterized clinically by the onset of syncopes or sudden
      death related to ventricular tachyarrhythmias in patients with a structurally
      normal heart. Its electrocardiographic features include right bundle branch bloc
      and ST-segment elevations in the precordial leads V1-V3. The estimated prevalence
      is 1 per 1000 in Asian countries and probably lower elsewhere: Asia is probably a
      birthplace of the syndrome. Its transmission is autosomal dominant with variable
      penetrance. Mutations have been identified in a gene coding for the alpha subunit
      of the sodium channel (SCN5A) in only 25% of cases. These genetic abnormalities
      cause a reduction of the density of the sodium current and explain the
      aggravation of electrocardiographic abnormalities caused by antiarrhythmic sodium
      channel blockers. Prognosis is very serious in symptomatic patients: prevention
      of sudden death requires implantation of an automatic defibrillator. The
      treatment decision is much more difficult for asymptomatic subjects with no
      family history.

PMID- 17446040
TI  - Evaluation of an alkaline phosphatase-labeled oligonucleotide probe for detection
      and enumeration of vibrio spp. from shrimp hatchery environment.
AB  - An alkaline phosphatase (AP)-labeled genus-specific oligonucleotide probe was
      developed to detect and enumerate vibrios in shrimp larvae and their surrounding
      environment. The probe was evaluated using 35 laboratory isolates of Vibrio
      species and 29 isolates of non-vibrio species. The probe was specific for the
      Vibrio species and no cross reaction was found with the non-vibrios included in
      the study. The total Vibrio counts obtained by plating on thiosulfate-citrate
      bile salts-sucrose agar (TCBS) and using oligonucleotide probe were compared.
      Total Vibrio counts obtained by probe were comparatively higher than the counts
      obtained by plating on TCBS agar. The difference between the counts obtained by
      the probe and by plating on TCBS agar ranged from 2 to 21 times. The study
      reveals that the use of a non-selective medium such as T1N3 agar followed by
      detection using a genus-specific probe would help to precisely enumerate the
      total Vibrio load in the aquaculture environments.

PMID- 17446039
TI  - Neurocognitive and neuroimaging correlates of pediatric traumatic brain injury: a
      diffusion tensor imaging (DTI) study.
AB  - This study examined the sensitivity of diffusion tensor imaging (DTI) to
      microstructural white matter (WM) damage in mild and moderate pediatric traumatic
      brain injury (TBI). Fourteen children with TBI and 14 controls ages 10-18 had DTI
      scans and neurocognitive evaluations at 6-12 months post-injury. Groups did not
      differ in intelligence, but children with TBI showed slower processing speed,
      working memory and executive deficits, and greater behavioral dysregulation. The
      TBI group had lower fractional anisotropy (FA) in three WM regions: inferior
      frontal, superior frontal, and supracallosal. There were no group differences in
      corpus callosum. FA in the frontal and supracallosal regions was correlated with
      executive functioning. Supracallosal FA was also correlated with motor speed.
      Behavior ratings showed correlations with supracallosal FA. Parent-reported
      executive deficits were inversely correlated with FA. Results suggest that DTI
      measures are sensitive to long-term WM changes and associated with cognitive
      functioning following pediatric TBI.

PMID- 17446042
TI  - Context-dependent retrieval of information by neural-network dynamics with
      continuous attractors.
AB  - Memory retrieval in neural networks has traditionally been described by dynamic
      systems with discrete attractors. However, recent neurophysiological findings of
      graded persistent activity suggest that memory retrieval in the brain is more
      likely to be described by dynamic systems with continuous attractors. To explore
      what sort of information processing is achieved by continuous-attractor dynamics,
      keyword extraction from documents by a network of bistable neurons, which gives
      robust continuous attractors, is examined. Given an associative network of terms,
      a continuous attractor led by propagation of neuronal activation in this network
      appears to represent keywords that express underlying meaning of a document
      encoded in the initial state of the network-activation pattern. A dominant
      hypothesis in cognitive psychology is that long-term memory is archived in the
      network structure, which resembles associative networks of terms. Our results
      suggest that keyword extraction by the neural-network dynamics with continuous
      attractors might symbolically represent context-dependent retrieval of short-term
      memory from long-term memory in the brain.

PMID- 17446043
TI  - A neural model of decision-making by the superior colicullus in an antisaccade
      task.
AB  - In the antisaccade paradigm subjects are instructed to perform eye movements in
      the opposite direction from the location of a visually appearing stimulus while
      they are fixating on a central stimulus. A recent study investigated saccade
      reaction times (SRTs) and percentages of erroneous prosaccades (towards the
      peripheral stimulus) of 2006 young men performing visually guided antisaccades. A
      unimodal distribution of SRTs (ranging from 80 to 600 ms) as well as an overall
      25% of erroneous prosaccade responses was reported in that large sample. In this
      article, we present a neural model of saccade initiation based on competitive
      integration of planned and reactive saccade decision signals in the intermediate
      layer of the superior colliculus. In the model the decision processes grow
      nonlinearly towards a preset criterion level and when they cross it, a movement
      is initiated. The resultant model reproduced the unimodal distributions of SRTs
      for correct antisaccades and erroneous prosaccades as well as the variability of
      SRTs and the percentage of erroneous prosaccade responses.

PMID- 17446041
TI  - Differential localization of the GluR1 and GluR2 subunits of the AMPA-type
      glutamate receptor among striatal neuron types in rats.
AB  - Differences among the various striatal projection neuron and interneuron types in
      cortical input, function, and vulnerability to degenerative insults may be
      related to differences among them in AMPA-type glutamate receptor abundance and
      subunit configuration. We therefore used immunolabeling to assess the frequency
      and abundance of GluR1 and GluR2, the most common AMPA subunits in striatum, in
      the main striatal neuron types. All neurons projecting to the external pallidum
      (GPe), internal pallidum (GPi) or substantia nigra, as identified by retrograde
      labeling, possessed perikaryal GluR2, while GluR1 was more common in striato-GPe
      than striato-GPi perikarya. The frequency and intensity of immunostaining
      indicated the rank order of their perikaryal GluR1:GluR2 ratio to be striato
      GPe>striatonigral>striato-GPi. Ultrastructural studies suggested a differential
      localization of GluR1 and GluR2 to striatal projection neuron dendritic spines as
      well, with GluR1 seemingly more common in striato-GPe spines and GluR2 more
      common in striato-GPi and/or striatonigral spines. Comparisons among projection
      neurons and interneurons revealed GluR1 to be most common and abundant in
      parvalbuminergic interneurons, and GluR2 most common and abundant in projection
      neurons, with the rank order for the GluR1:GluR2 ratio being parvalbuminergic
      interneurons>calretinergic interneurons>cholinergic interneurons>projection
      neurons>somatostatinergic interneurons. Striosomal projection neurons had a
      higher GluR1:GluR2 ratio than did matrix projection neurons. The abundance of
      both GluR1 and GluR2 in striatal parvalbuminergic interneurons and projection
      neurons is consistent with their prominent cortical input and susceptibility to
      excitotoxic insult, while differences in GluR1:GluR2 ratio among projection
      neurons are likely to yield differences in Ca(2+) permeability, desensitization,
      and single channel current, which may contribute to differences among them in
      plasticity, synaptic integration, and excitotoxic vulnerability. The apparent
      association of the GluR1 subunit with synaptic plasticity, in particular,
      suggests striato-GPe neuron spines as a particular site of corticostriatal
      synaptic plasticity, presumably associated with motor learning.

PMID- 17446044
TI  - Caveolin-1 phosphorylation is required for stretch-induced EGFR and Akt
      activation in mesangial cells.
AB  - Increased glomerular hydrostatic pressure is an important determinant of
      glomerulosclerosis and can be modeled in vitro by exposure of mesangial cells
      (MC) to cyclic mechanical strain. We have recently shown that Akt mediates the
      stretch-induced production of type I collagen, an important contributor to
      sclerosis, in MC. Here we studied the upstream mediators of Akt activation.
      Primary rat MC were exposed to 1 Hz cyclic strain for 10 min, previously shown to
      induce maximal Akt activation. Neither the integrin inhibitor GRDGSP nor
      cytoskeletal disruptors had any effect on stretch-induced Akt activation. Akt
      activation was, however, mediated by transactivation of the epidermal growth
      factor receptor (EGFR), and this required receptor kinase activity since Akt
      activation did not occur in cells expressing kinase-dead EGFR (K721A). Src was
      further shown to be upstream of the EGFR, with its inhibitor SU6656 preventing
      both EGFR and Akt activation. The membrane microdomains caveolae were found to be
      required for this signaling to occur. Chemical disruption of caveolae with
      cyclodextrin or filipin prevented Akt activation, and both EGFR and Akt
      activation were lost in caveolin-1 (cav-1) knockout MC. The latter was rescued
      with reexpression of cav-1. Further, Src-mediated phosphorylation of cav-1 on Y14
      was required for stretch-induced EGFR and Akt activation, since these were
      abrogated in MC expressing the nonphosphorylatable cav-1 Y14A mutant. Thus,
      mechanical strain-induced activation of Akt in MC is independent of integrin
      activation and the actin cytoskeleton, but depends upon EGFR transactivation.
      EGFR transactivation requires intact caveolae and the Src-mediated
      phosphorylation of cav-1 on Y14. These studies define a novel function for cav-1
      and caveolae in EGFR transactivation leading to Akt activation by mechanical
      stress.

PMID- 17446045
TI  - Visuospatial memory deficits in adolescent onset schizophrenia.
AB  - Visuospatial memory encoding deficits have been reported in adults with
      schizophrenia, while adolescents with schizophrenia have not been specifically
      investigated with visuospatial memory encoding and retrieval paradigms. A cross
      sectional study of delayed matching-to-sample performance in 19 right handed,
      male, anti-psychotic medication naive adolescents with undifferentiated
      schizophrenia and 28 age, gender, IQ and handedness matched healthy participants
      was completed. The adolescent-onset schizophrenia group demonstrated significant
      impairment in visuospatial memory, independent of the degree of delay, consistent
      with an encoding impairment. The impaired encoding phase of visuospatial memory
      in the adolescent-onset schizophrenia group is consistent with findings in adult
      onset schizophrenia samples, suggesting a developmental stage-independent
      deficit.

PMID- 17446046
TI  - Influence of capsule and extended-spectrum beta-lactamases encoding plasmids upon
      Klebsiella pneumoniae adhesion.
AB  - Interaction with cells is believed to be a crucial step in the process of
      colonization by Klebsiella pneumoniae. In this study, we investigated the
      adhesion properties of 17 extended-spectrum beta-lactamases (ESBLs) producing
      clinical isolates using 2 intestinal cells (Int-407 and HT-29 cells) and
      components of the extracellular matrix (ECM) (fibrinogen, collagen, fibronectin).
      Since the capsule formed by K. pneumoniae potentially masks bacterial cell
      surface components, we created mutants defective in capsular synthesis. The
      levels of adhesion of the acapsulated mutants were higher than their
      corresponding wild-type strains for 7 and 4 isolates with Int-407 and HT-29
      cells, respectively, whereas 2 mutants displayed lower adhesion indexes with HT
      29 cells. Nine mutants adhered at higher levels than their corresponding wild
      type strains to all 3 components of ECM tested and 13 only to collagen. Transfer
      by mating of ESBL-encoding plasmids did not correlate with the acquisition of
      adhesive properties by the transconjugants, which suggests that these plasmids
      were not involved in adhesion expression. The presence of ESBL-encoding plasmids
      alters the basal adhesion capacity of the recipient strain, and cured strains
      adhered more than the parental strains. The possessing of capsule or plasmid
      encoded factors would have a bacterial cost, including a weaker capacity for
      adhesion.

PMID- 17446047
TI  - Mutations affecting the biogenesis of the AIDA-I autotransporter.
AB  - Autotransporters are simple systems that Gram-negative bacteria employ to secrete
      proteins to their surfaces or into the extracellular milieu. They consist of an N
      terminal passenger domain and a C-terminal domain that is thought to insert into
      the outer membrane and mediate the secretion of the passenger domain. Despite the
      apparent simplicity of these secretion systems, their mechanism of translocation
      is still not completely understood. To study this mechanism, we used the AIDA-I
      autotransporter adhesin of Escherichia coli. We introduced mutations at several
      sites in a junction region of the passenger domain, close to the membrane
      embedded domain. We observed that the mutations dramatically affected the
      biogenesis of AIDA-I. The same mutations, however, did not affect the
      translocation of a chimeric construct where MalE, the E. coli periplasmic maltose
      binding protein, replaced most of the passenger domain of AIDA-I. Our results
      emphasize the function of this region in the biogenesis of AIDA-I and suggest
      that it plays its role by interacting with and/or promoting folding of native
      passenger domains.

PMID- 17446048
TI  - German guidelines for the diagnosis and management of infective endocarditis.
AB  - This Gudelines are the translation of the German Guidelines for the Diagnosis and
      Management of Infective Endocarditis, which were prepared by the Working Group on
      Infective Endocarditis of the Paul-Ehrlich-Society and the German Society for
      Cardiology, Heart, and Circulatory Research in cooperation with the Deutsche
      Gesellschaft fur Thorax-, Herz und Gefasschirurgie (DGTHG; German Society for
      Thorax-, Cardiac-, and Vascular Surgery), the Deutsche Gesellschaft fur
      Infektiologie (DGI; German Society for Infectious Diseases), the Deutsche
      Gesellschaft fur Internistische Intensivmedizin und Notfallmedizin (DGIIN; German
      Society for Internal Intensive Care Medicin and Emergency Medicine), the Deutsche
      Gesellschaft fur Hygiene und Mikrobiologie (DGHM; German Society for Hygiene and
      Microbiology) and the Deutsche Gesellschaft fur Innere Medizin (DGIM; German
      Society for Internal Medicine) (Naber CK et al. [S2 Guideline for diagnosis and
      therapy of infectious endocarditis] Z Kardiol. 2004;93:1005-21). The Guidelines
      provide recommendations for the diagnosis and management of infective
      endocarditis.

PMID- 17446050
TI  - Studies on oral absorption of stearic acid SLN by a novel fluorometric method.
AB  - In this study, the fluorescein isothiocyanate (FITC) labeled otcadecylamine
      (ODA), otcadecylamine-fluorescein isothiocyanate (ODA-FITC), was synthesized and
      used as a fluorescence marker to be incorporated into stearic acid solid lipid
      nanoparticles (SLN) by solvent diffusion method. Approximately 97.9% of added ODA
      FITC was incorporated into SLN. Under sink condition, approximately 7% and less
      than 3% of ODA-FITC leaked from SLN in 24 h, when the ODA-FITC loaded SLNs were
      dispersed in plasma or phosphate buffered saline (PBS, pH 6.8) containing 0.3 wt%
      sodium dodecyl sulfate (SDS), respectively. The ODA-FITC loaded SLNs were then
      subjected to the in vivo transport experiments. The results showed that the
      transport efficiency of SLN by oral administration was 30%. The SLN could be
      extensively absorbed, and indicated a linear absorption mechanism in
      gastrointestinal tract within certain range of concentrations. By the external
      diversion experiments on lymph, it showed that approximately 77.9% of absorbed
      SLN was transported into systematic circulation via lymph, which is a major SLN
      transport pathway in gastrointestinal tract. The rest of absorbed SLN was
      transported directly into blood, which might be through capillary vessel or
      intestinal epithelial cell by paracellular pathway. The further experiment
      demonstrated that the polyethylene glycol monostearate (PEG2000-SA)-modified SLN
      could also be absorbed in gastrointestinal tract and achieved a prolonged effect
      in vivo.

PMID- 17446051
TI  - A facile entrapment approach to construct PEGylated polyplexes for improving
      stability in physiological condition.
AB  - PEGylated polyplexes had been proved to improve the stability of DNA complexes.
      However, the conjugation reaction might reduce the capacity of efficient DNA
      complexation. Herein we described an easy and favorable approach to construct
      PEGylated polyplexes via entrapping poly(ethylene glycol) cholesterol ether
      (CPEG) into polyplexes. It was of interest to find the addition sequence of CPEG
      had great effect on the stability of polyplexes in physiological salt
      concentration. The addition of CPEG into the formed PEI(25k)/DNA polyplexes had
      no effect to improve the stability. Whereas by the "CPEG first" method of adding
      CPEG and PEI(25k) mixture into the DNA solution, the PEI(25k)/CPEG/DNA polyplexes
      showed excellent anti-aggregation effect and enhanced transfection efficiency in
      physiological condition. The difference performance might be explained by the
      possibility of CPEG entrapment. By the "CPEG first" method, PEGylated polyplexes
      was constructed due to the hydrophobic interaction between the cholesterol group
      of CPEG and hydrophobic charged-compensated core. The PEG coating significantly
      improved the stability of polyplexes in physiological condition. This facile
      entrapment approach to prepare PEGylated polyplexes might have great potential in
      non-viral gene delivery research and application.

PMID- 17446052
TI  - [Diagnostic approach and treatment of neonates and children cholestasis].

PMID- 17446049
TI  - Non-selective cation channels, transient receptor potential channels and ischemic
      stroke.
AB  - Several pathways to neural cell death are involved in ischemic stroke, and all
      require monovalent or divalent cation influx, implicating non-selective cation
      (NC) channels. NC channels are also likely to be involved in the dysfunction of
      vascular endothelial cells that leads to formation of edema following cerebral
      ischemia. Two newly described NC channels have emerged as potential participants
      in ischemic stroke, the acid sensing ion channel (ASIC), and the sulfonylurea
      receptor-1 (SUR1)-regulated NC(Ca-ATP) channel. Non-specific blockers of NC
      channels, including pinokalant (LOE 908 MS) and rimonabant (SR141716A), have
      beneficial effects in rodent models of ischemic stroke. Evidence is accumulating
      that NC channels formed by members of the transient receptor potential (TRP)
      family are also up-regulated in ischemic stroke and may play a direct role in
      calcium-mediated neuronal death. The nascent field of NC channels, including TRP
      channels, in ischemic stroke is poised to provide novel mechanistic insights and
      therapeutic strategies for this often devastating human condition.

PMID- 17446053
TI  - [Exercise test for asthmatic children. For whom? What indications?].
AB  - Asthma in children is not the most important indication for an exercise test.
      However, one might recommend a cardiopulmonary exercise test systematically in
      the follow-up of patients with severe asthma when there is persistent bronchial
      obstruction, when an asthmatic child complains of dyspnoea on exertion, or when
      the child's physical activity is limited. This test could be used to assess
      exercise tolerance, ventilatory adaptations, and the need for exercise training.
      Follow-up and evaluation of this training could be through a field exercise test
      (shuttle test or walk test). Moreover, the diagnosis of childhood asthma is
      frequently based only on symptoms suggestive of exercise-induced asthma. When the
      clinical features or a bronchodilatator test are not diagnostic, analysis of
      symptoms occurring during an exercise test can establish the diagnosis. The
      exercise test is thus a method that provides the time and intensity necessary to
      trigger exercise-induced bronchospasm.

PMID- 17446054
TI  - [Norman epidemics: MenBvac vaccine].

PMID- 17446055
TI  - [New guidelines for care and investigation of sudden unexpected deaths in
      infant].

PMID- 17446056
TI  - [Uveitis of children: a report of 18 cases].
AB  - Childhood uveitis is a rare but serious disease that may causes visual loss.
      Causes are various and an underlying disease is not always found. PURPOSE: To
      analyse clinical features and prognosis of uveitis in children. PATIENTS AND
      METHODS: A retrospective, descriptive study of cases observed in a general
      pediatric unit over a period of 15 years (1990-2005) at Tunis. RESULTS: We
      gathered 18 cases of uveitis (girls 55.6% ,boys 44.4%). Mean age at the diagnosis
      was 8+/-3 years. Diagnosis was made after a decreased of visual acuity in 55.6%
      of cases. Localization of uveitis was anterior (6 cases), intermediate (1 case),
      posterior (3 cases) and total (8 cases). An underlying disease was found in only
      5 patients: Behcet's disease (3 patients), juvenile chronic arthritis (1
      patient), possible dermatopolymyositis (1 patient). The evolution was favorable
      in 10 cases with local treatment, systemic corticotherapy and/or
      immunosuppressive agents. Complications occurred in 3 cases. CONCLUSION: Causes
      of uveitis in childhood remains most often undiagnosed Our study illustrates the
      pending risk of severe visual impairment and strict ophtalmology follow-up is
      mandatory.

PMID- 17446057
TI  - Antihypertensive effect of a standardized aqueous extract of Cecropia glaziovii
      Sneth in rats: an in vivo approach to the hypotensive mechanism.
AB  - Cecropia glaziovii Sneth is a common tree at the Southeastern Brazilian coast. As
      many other species of the genus, it shares the reputed folk use to treat heart
      failure, cough, asthma and bronchitis. The plant has been cultivated under
      controlled conditions and the 2% aqueous extract (AE) prepared with the dried
      leaves was standardized by its chemical contents on catechins, flavonoids and
      procyanidins. The present paper reports the antihypertensive activity of AE and
      of n-butanol fraction (BuF), an enriched semi-purified butanolic fraction used to
      isolate the main chemical constituents. Oral administration of AE and BuF induced
      hypotension in normotensive rats. The effect of AE (0.5 g/kg/bi, p.o.) was time
      and dose-dependent peaking at 2-3 weeks after daily administration. BuF was
      faster but not more active than AE. Both extracts decreased the hypertension of
      spontaneous hypertensive rats, the hypertension induced in rats by L-NAME
      treatment and that induced by constriction of one renal artery. The
      antihypertensive effect was maintained for as long as 60 days of treatment and
      was reversible upon drug washout at the same rate of its establishment. Acute
      i.v. administration of BuF to anesthetized rats induced a fast short-lasting
      hypotension and inhibited the pressor responses to noradrenaline, angiotensin I
      and angiotensin II by 40%. These results were indirect indications that the
      hypotension induced by AE is not related to ACE inhibition, increased NO
      synthesis, or specific blockade of alpha1 and AT1 receptors. It can be suggested
      that BuF interferes with the calcium handling mechanisms in smooth muscle cells
      and neurons. Intravenous injection of five out of nine compounds isolated from
      BuF produced immediate but short-lasting hypotension that does not correlate with
      the onset of the hypotension after oral treatment. This finding suggests that
      they may not be the compounds directly responsible for the delayed and sustained
      hypotension after per os administration of AE. The many compounds isolated from
      AE are under evaluation to determine its pharmacokinetics, mechanisms of action
      and interactions necessary to yield the plant effect. Although its mechanism is
      still unknown, AE seems to be an effective and safe antihypertensive
      phytomedicine.

PMID- 17446058
TI  - Potential biomarkers for diagnosis of sarcoidosis using proteomics in serum.
AB  - BACKGROUND: Sarcoidosis is a multi-systemic inflammatory disorder, which affects
      the lungs in 90% of the cases. The main pathologic feature is chronic
      inflammation resulting in non-caseating granuloma formation. Until now there is
      no satisfying biomarker for diagnosis or prognosis of sarcoidosis. This study is
      focused on the detection of potential biomarkers in serum for the diagnosis of
      sarcoidosis using surface-enhanced laser desorption ionization-time of flight
      mass spectrometry (SELDI-TOF-MS). METHODS: For detection of potential biomarkers,
      protein profiles of anion exchange fractionated serum of 35 sarcoidosis patients
      and 35 healthy controls were compared using SELDI-TOF-MS. Sensitivities and
      specificities of the potential biomarkers obtained with SELDI-TOF-MS, generated
      with decision tree algorithm, were compared to the conventional markers
      angiotensin converting enzyme (ACE) and soluble interleukin-2 receptor (sIL-2R).
      RESULTS: Optimal classification was achieved with metal affinity binding arrays.
      A single marker with a mass-to-charge (m/z) value of 11,955 resulted in a
      sensitivity and specificity of 86% and 63%, respectively. A multimarker approach
      of two peaks, m/z values of 11,734 and 17,377, resulted in a sensitivity and
      specificity of 74% and 71%, respectively. These sensitivities and specificities
      were higher compared to measurements of ACE and sIL-2R. Identification of the
      peak at m/z 17,377 resulted in the alpha-2chain of haptoglobin. CONCLUSIONS: This
      study acts as a proof-of-principle for the use of SELDI-TOF-MS in the detection
      of new biomarkers for sarcoidosis. The peak of the multimarker at m/z 17,377 was
      identified as the alpha-2chain of haptoglobin.

PMID- 17446060
TI  - Helicobacter pylori infection, interleukin-1 gene polymorphisms and the risk of
      colorectal cancer: evidence from a case-control study in Germany.
AB  - Helicobacter pylori infection is a strong risk factor for gastric cancer. A
      positive association with colorectal cancer has also been suggested, but
      available evidence remains inconclusive. In this population-based case-control
      study we investigated the association between H. pylori seroprevalence and
      colorectal adenocarcinoma under consideration of pro-inflammatory gene
      polymorphisms (384 incident cancer patients, 467 matched control subjects).
      Overall, the H. pylori seroprevalence was higher among cases (51%) than among
      controls (44%), and a positive association between H. pylori seroprevalence and
      colorectal adenocarcinoma risk was found, that persisted after adjustment for
      known potential confounders, including measures of socioeconomic status (odds
      ratio (OR)=1.41; 95% confidence intervals (CI), 1.06-1.87). Presence of specific
      H. pylori cytotoxin-associated gene A (CagA) antibodies did not significantly
      affect the observed risk. Additionally, a pro-inflammatory genotype did not
      increase the colorectal cancer risk associated with H. pylori infection. H.
      pylori positive subjects carrying the pro-inflammatory genotypes even had a lower
      risk.

PMID- 17446059
TI  - Epigallocatechin-3-gallate suppresses NF-kappaB activation and phosphorylation of
      p38 MAPK and JNK in human astrocytoma U373MG cells.
AB  - Epigallocatechin-3-gallate (EGCG) is the major polyphenol component of green tea
      and is primarily responsible for the green tea effect. EGCG possesses two
      triphenolic groups in its structure. These groups are reported to be important
      with respect to anticarcinogenic and antioxidant effects. However, the anti
      inflammatory effect of EGCG on Alzheimer's disease (AD) is still not fully
      understood. In this study, we investigated the effects of EGCG in attenuating the
      inflammatory response induced by interleukin (IL)-1beta+beta-amyloid (25-35)
      fragment (Abeta) in human astrocytoma, U373MG cells. EGCG significantly inhibited
      the IL-1beta+Abeta (25-35)-induced IL-6, IL-8, vascular endothelial growth factor
      (VEGF) and prostaglandin (PG)E(2) production at 24 h (P<.01). The maximal
      inhibition rate of IL-6, IL-8, VEGF and PGE(2) production by EGCG was
      approximately 54.40%, 56.01%, 69.06% and 47.03%, respectively. EGCG also
      attenuated the expression of cyclooxygenase-2 and activation of nuclear factor
      kappaB induced by IL-1beta+Abeta (25-35). We demonstrated that EGCG suppresses IL
      1beta+Abeta (25-35)-induced phosphorylation of the mitogen-activated protein
      kinase p38 and the c-Jun N-terminal kinase. In addition, EGCG induced the
      expression of mitogen-activated protein kinase phosphatase-1. These results
      provide new insight into the pharmacological actions of EGCG and its potential
      therapeutic application to various neurodegenerative diseases such as AD.

PMID- 17446061
TI  - Versican expression in human cervical cancer.
AB  - Versican expression may enhance tumour invasion and metastasis. However, the
      expressions of versican in cervical cancer have seldom been characterised. The
      aim of this study was to investigate versican expression in human cervical
      cancers. We immunohistochemically investigated the expression of versican protein
      in 174 cervical cancers and analysed the correlation with various
      clinicopathological features, including patient outcome. Stromal versican
      expression was significantly higher in patients with lymph node metastasis
      (p<0.0001). Epithelial versican expression was significantly higher in patients
      with non-squamous cell cercinoma (p=0.0003), lymph-vascular space invasion
      (p=0.046), lymph node metastasis (p=0.009) and ovarian metastasis (p=0.0001).
      Multivariate analysis showed that high epithelial versican expression was an
      independent prognostic factor for disease-free survival. Versican enrichment of
      the tumour tissue may be associated with progression in cervical cancer. Versican
      expression can serve as an indicator of poor prognosis in patients with cervical
      cancer.

PMID- 17446062
TI  - Antisense treatment of IGF-IR induces apoptosis and enhances chemosensitivity in
      central nervous system atypical teratoid/rhabdoid tumours cells.
AB  - Central nervous system (CNS) atypical teratoid/rhabdoid tumours (AT/RT) are among
      the paediatric malignant tumours with the worst prognosis and fatal outcome.
      Insulin-like growth factor I receptor (IGF-IR) protects cancer cells from
      apoptosis induced by a variety of anticancer drugs and radiation. In the present
      study, IGF-IR was expressed in 8/8 primary AT/RT as detected by
      immunohistochemistry. Moreover, we found IGF-I and IGF-II mRNA in BT-16 CNS AT/RT
      cells and IGF-II mRNA in BT-12 CNS AT/RT cells, and autophosphorylated IGF-IR in
      both cell lines, indicating the potential presence of an autocrine/paracrine IGF
      I/II/IGF-IR loop in CNS AT/RT. IGF-IR antisense oligonucleotide treatment of
      human CNS AT/RT cells resulted in significant down-regulation of IGF-IR mRNA and
      protein expression, induction of apoptosis, and chemosensitisation to doxorubicin
      and cisplatin. These studies provide evidence for the influence of IGF-IR on
      cellular responses to chemotherapy and raise the possibility that curability of
      selected CNS AT/RT may be improved by pharmaceutical strategies directed towards
      the IGF-IR.

PMID- 17446063
TI  - Succinoylation of sugarcane bagasse under ultrasound irradiation.
AB  - The chemical modification of sugarcane bagasse with succinic anhydride using
      pyridine as solvent after ultrasound irradiation was studied. The optimized
      parameters included ultrasound irradiating time 0-50 min, reaction time 30-120
      min, succinic anhydride concentration by the ratio of dried sugarcane bagasse to
      succinic anhydride from 1:0.25 to 1:1.50, and reaction temperature 75-115 degrees
      C are required in the process. The extent of succinoylation was measured by the
      weight percent gain (WPG), which increased with increments of reaction time,
      succinic anhydride concentration, and reaction temperature. The ultrasound
      irradiation has a positive effect on bagasse succinoylation process. On the other
      hand, the ultrasonic pre-treatment application broke down the cell wall polymers,
      resulting in, therefore, a negative effect on the WPG. Evidences of
      succinoylation were also provided by FT-IR and CP MAS (13)C NMR and the results
      showed that the succinoylation at C-2 and C-3 occurred. The thermal stability of
      the succinylated bagasse decreased upon chemical modification.

PMID- 17446064
TI  - Structural study of the fulvic fraction during composting of activated sludge
      plant matter: elemental analysis, FTIR and 13C NMR.
AB  - The starting fulvic structures isolated from an initial mixture of activated
      sludge and plant matter presented abundant peptide structures and hydrocarbons
      that absorb in FTIR spectra around (1650 and 1560 cm(-1)) and 1072 cm(-1),
      respectively. They also present a high resonance signal in the O- and N-alkyl
      areas of (13)C NMR spectra. As composting proceeded, some changes led to the
      formation of the molecular structures of fulvic fraction as demonstrated by a
      decrease of intensity of compounds absorbing around 1072 cm(-1) and an increase
      of those absorbing around 1140 cm(-1). The resonance of O- and N-substituted
      alkyl carbon also decreased from 55.7% to 33.8%, with an increase in the
      intensity of aromatic carbons, alkyls and carboxyls. These data indicate that the
      microbial community that developed during composting used polysaccharides as an
      energy source, structures which are supplied in abundance in the initial
      material. The fulvic fraction of the final compost is much richer in aromatic
      structures and aliphatic ethers/esters, which are most likely preserved from the
      original material but probably also synthesized through the microbial activities.
      The occurrence of alkyl ethers/esters at the end of composting is demonstrated by
      strong absorbance around 1140 cm(-1) in the FTIR spectra and large peaks at 32
      and 174 ppm in the NMR spectra. These structures could also be produced following
      the creation of ether/ester bonds during the humification process.

PMID- 17446065
TI  - Production of schizophyllan using Schizophyllum commune NRCM.
AB  - In the present work, four strains were screened for schizophyllan production, of
      which Schizophyllum commune NRCM was selected for further work. The fermentation
      was carried out for 168 h at 28+/-2 degrees C on an orbital shaker at 180 rpm. In
      the first step, one factor-at-a-time method was used to investigate the effect of
      media constituents such as carbon and nitrogen sources on schizophyllan
      production. Subsequently in the second step, concentration of the medium
      components was optimized using Response Surface Method (RSM). The yield increased
      from 3.25+/-0.72 g/l in the unoptimized media to 8.03+/-1.12 g/l in the medium
      optimized by RSM.

PMID- 17446066
TI  - Characterizing the conservation effect of clear coatings on photodegradation of
      wood.
AB  - Photodiscoloration of clear-coated wood may be caused by the yellowing of both
      clear coating film and underlying wood, or either of them. Wood specimens covered
      with two types of free polyurethane films with/without light stabilizer were used
      to simulate the photodiscoloration of clear-coated wood. Percent UV transmission
      of aromatic polyurethane (PU) films decreased after irradiation, whereas
      aliphatic polyurethane (PUA) films significantly increased with irradiation time
      resulting in further photoyellowing of wood beneath the PUA film. A light
      reflection model was used to elucidate discoloration caused separately by the
      clear coating film and the underlying wood. After 24 days of light irradiation,
      clear coating and the underlying wood contributed respectively, 40.70% and 59.30%
      discoloration of PU-coated specimens, and the corresponding values for PUA-coated
      specimens were 5.15% and 94.85%. PU film with light stabilizer reduced lignin
      degradation and generation of carbonyl derivatives in the underlying wood.

PMID- 17446067
TI  - A universal kinetic model for characterisation of the effect of chip thickness on
      kraft pulping.
AB  - A kinetic model was developed to characterise the heterogeneous nature of kraft
      delignification kinetics, taking into account the effect of chip thickness. The
      final form of the model applied to kraft delignification can be represented by a
      first-order rate equation with a rate constant inversely proportional to a power
      function of chip thickness. Published laboratory results from kraft pulping of
      various lignocellulosic materials were used to validate the model. The outcomes
      confirm the significant effect of chip thickness on the delignification rate. The
      resultant model was used to predict the effect of chip thickness on the kappa
      distribution of kraft pulps.

PMID- 17446068
TI  - Nutritional composition of frog (Rana esculanta) waste meal.
AB  - In the present study, the waste obtained from the frozen frog leg industry was
      used for the production of frog waste meal, and its proximate, amino acids, fatty
      acids, mineral and vitamin compositions were evaluated to determine the
      nutritional quality. In addition, the total bacterial count, Salmonella, total
      volatile basic nitrogen (TVB-N, mgN/100g) and thiobarbituric acid (TBA, mg
      malonaldehyde/kg) were also measured to determine the microbiological and
      chemical quality of frog waste meal (FWM). The crude protein, fat and ash content
      of FWM on a dry weight basis were 68.6%, 17.0% and 13.2%, respectively. The amino
      acid profiles were found to be fairly close to those of fish meal in terms of
      protein sources and rich in the glutamic acid, glycine, proline, arginine, and
      methionine. The proportions of fatty acid composition in FWM were analysed and
      findings were 26.7% for total saturated fatty acid (SFA), 42.5% for total
      monounsaturated fatty acid (MUFA), 17.0% for total n - 6 and 3.3% for n - 3
      ratio. The major SFA, MUFA and PUFA in FWM were palmitic acid (19.1%), oleic acid
      (26.0%) and linoleic acid (16.7%), respectively. FWM was found to be high in
      mineral content, especially Zn, K, Cu, Mn, and Mg and high level of some vitamins
      such as folic acids and thiamin. The total bacterial count was found to be
      2.9x10(4) CFU/g, and Salmonella was not observed. TVB-N and TBA in FWM was
      determined to be 157.4+/-5.8 mg N/100g and 1.2+/-0.1 mg malonaldehyde/kg,
      respectively.

PMID- 17446069
TI  - Synthesis and biological evaluation of 2beta,3alpha-(substituted
      phenyl)nortropanes as potential norepinephrine transporter imaging agents.
AB  - A series of 2beta,3alpha-(substituted phenyl)nortropanes was synthesized and
      evaluated in vitro for human monoamine transporters. All compounds studied in
      this series exhibited nanomolar potency for the norepinephrine transporter (NET).
      Radiolabeling and nonhuman primate microPET brain imaging studies were performed
      with the most promising compound, [(11)C]1, to determine its utility as a NET
      imaging agent. Despite high in vitro affinity for the human NET, the high uptake
      of [(11)C]1 in the caudate and putamen excludes its use as an in vivo PET imaging
      agent for the NET.

PMID- 17446070
TI  - Synthesis and biological evaluation of nitric oxide-releasing derivatives of
      oleanolic acid as inhibitors of HepG2 cell apoptosis.
AB  - A total of 106 nitric oxide-releasing derivatives of oleanolic acid were
      synthesized and their effects on the inhibition of anti-Fas-mediated HepG2 cell
      apoptosis were evaluated in vitro. Several compounds inhibited anti-Fas-mediated
      HepG2 cell apoptosis in a dose-dependent manner. Within this series of compounds,
      8b is the most potent inhibitor. The development of new NO-releasing derivatives
      of oleanolic acid may aid in the design of NO-based medicines for the
      intervention of human liver inflammatory diseases.

PMID- 17446071
TI  - Discovery of heterobicyclic templates for novel metabotropic glutamate receptor
      subtype 5 antagonists.
AB  - Investigation of a series of heterobicyclic compounds with essential
      pharmacophoric features of the metabotropic glutamate receptor 5 (mGluR5)
      antagonists MPEP and MTEP provided novel structural templates with sub-micromolar
      affinities at the mGluR5.

PMID- 17446072
TI  - Structure-activity relationships of novel, highly potent, selective, and orally
      active CCR1 antagonists.
AB  - Design and synthesis of a series of 3-amino-4-(2-(2-(4-benzylpiperazin-1-yl)-2
      oxoethoxy)phenylamino)cyclobutenedione derivatives as novel CCR1 antagonists are
      described. Structure-activity relationship studies led to the identification of
      compound 22, which demonstrated potent binding activity, functional antagonism of
      CCR1 as well as good species cross-reactivity. In addition, compound 22 also
      showed desirable pharmacokinetic profiles and was selected for in vivo studies in
      the mouse collagen-induced arthritis model.

PMID- 17446073
TI  - Synthesis and biological evaluation of an 123I-labeled bicyclic nucleoside
      analogue (BCNA) as potential SPECT tracer for VZV-tk reporter gene imaging.
AB  - An iodine-123 labeled bicyclic nucleoside analogue ([(123)I]-4) has been
      synthesized and evaluated as a potential single photon emission tomography
      (SPECT) reporter probe for the non-invasive imaging of expression of the
      varicella zoster virus thymidine kinase (VZV-tk) reporter gene. In vitro
      enzymatic assays revealed that the non-radioactive mono-iodo derivative 4 has
      good affinity for VZV-TK (IC(50): 4.2 microM). Biodistribution of [(123)I]-4 was
      examined in normal mice. Evaluation of [(123)I]-4 in HEK-293T cells showed 1.74
      fold higher accumulation in VZV-TK-expressing cells compared to control cells.

PMID- 17446075
TI  - Intensive care nurses' perceptions of protocol-directed weaning--a qualitative
      study.
AB  - The aim of this study was to identify intensive care nurses' perceptions of
      protocol-directed weaning, by means of focus group interviews and qualitative
      content analysis. The results showed that the nurses perceived the protocol as
      useful. When prescribed, it represented interprofessional agreement that allowed
      them to act in the absence of a physician. It focused on weaning, saved time, was
      easy to use and led to a feeling of safety and continuity in the weaning process.
      Barriers to its use were related to lack of instructions from physicians. Nurses
      reported three ways of handling the situation in the absence of a weaning plan:
      taking action, waiting, and giving weaning low priority, which could lead to
      undesired variations. Nurses in this study reported that they would like an
      interdisciplinary approach to weaning and expressed the need for a shared
      "language" or knowledge base in order to improve communication. It is important
      that different disciplines meet to share each other's knowledge. Contact is vital
      in order to learn about and respect different types of professional knowledge.

PMID- 17446074
TI  - Analysis of nucleolar protein dynamics reveals the nuclear degradation of
      ribosomal proteins.
AB  - BACKGROUND: The nucleolus is a subnuclear organelle in which rRNAs are
      transcribed, processed, and assembled with ribosomal proteins into ribosome
      subunits. Mass spectrometry combined with pulsed incorporation of stable isotopes
      of arginine and lysine was used to perform a quantitative and unbiased global
      analysis of the rates at which newly synthesized, endogenous proteins appear
      within mammalian nucleoli. RESULTS: Newly synthesized ribosomal proteins
      accumulated in nucleoli more quickly than other nucleolar components. Studies
      involving time-lapse fluorescence microscopy of stable HeLa cell lines expressing
      fluorescent-protein-tagged nucleolar factors also showed that ribosomal proteins
      accumulate more quickly than other components. Photobleaching and mass
      spectrometry experiments suggest that only a subset of newly synthesized
      ribosomal proteins are assembled into ribosomes and exported to the cytoplasm.
      Inhibition of the proteasome caused an accumulation of ribosomal proteins in the
      nucleus but not in the cytoplasm. Inhibition of rRNA transcription prior to
      proteasomal inhibition further increased the accumulation of ribosomal proteins
      in the nucleoplasm. CONCLUSIONS: Ribosomal proteins are expressed at high levels
      beyond that required for the typical rate of ribosome-subunit production and
      accumulate in the nucleolus more quickly than all other nucleolar components.
      This is balanced by continual degradation of unassembled ribosomal proteins in
      the nucleoplasm, thereby providing a mechanism for mammalian cells to ensure that
      ribosomal protein levels are never rate limiting for the efficient assembly of
      ribosome subunits. The dual time-lapse strategy used in this study, combining
      proteomics and imaging, provides a powerful approach for the quantitative
      analysis of the flux of newly synthesized proteins through a cell organelle.

PMID- 17446076
TI  - Synthesis, inhibition and binding of simple non-nitrogen inhibitors of monoamine
      transporters.
AB  - A series of simple truncated analogues of phenyl tropanes, 2-arylcycloalk-1-enyl
      carboxylic acid methylesters, were prepared and investigated for their activity
      towards the dopamine, serotonin and norepinephrine transporters. The compounds
      were prepared from cyclic ketoesters, which were converted to enolic triflates
      and reacted with arylboronates using the Suzuki coupling. For comparison the
      corresponding piperidines were also made and investigated. The new compounds
      inhibit monoamine-transporters with Ki values ranging from 0.1 to 1000 microM.

PMID- 17446077
TI  - 2,3,5-Substituted tetrahydrofurans as cancer chemopreventives. Part 1: synthesis
      and anti-cancer activities of 5-hydroxymethyl-2,3-diaryl-tetrahydro-furan-3-ols.
AB  - The allylation of appropriate benzoin in presence of indium metal followed by m
      CPBA mediated cyclization gave 5-hydroxymethyl-2,3-diaryl-tetrahydro-furan-3-ols.
      Investigations on 59 human tumor cell lines of these compounds identify four
      compounds exhibiting significant growth inhibition of tumor cells at particular
      cell lines. Compound 12 is very specific toward CCRF-CEM and SR cell lines of
      leukemia.

PMID- 17446078
TI  - Oxidation of C4-hydroxyphenyl 1,4-dihydropyridines in dimethylsulfoxide and its
      reactivity towards alkylperoxyl radicals in aqueous medium.
AB  - This work reports the electrochemical oxidation of three newly synthesized C4
      hydroxyphenyl-substituted 1,4-dihydropyridine derivatives in dimethylsulfoxide.
      The reactivity of the compounds with ABAP-derived alkylperoxyl radicals in
      aqueous buffer pH 7.4, was also studied. The oxidation mechanism involves the
      formation of the unstable dihydropyridyl radical, which was confirmed by
      controlled-potential electrolysis (CPE) and ESR experiments. The final product of
      the CPE, that is, pyridine derivative, was identified by GC-MS technique for the
      three derivatives. A direct reactivity of the synthesized compounds toward ABAP
      derived alkylperoxyl radicals was found. The pyridine derivative was identified
      by GC-MS as the final product of the reaction. Results reveal that this type of
      1,4-DHPs significantly reacts with the radicals, even compared with commercial
      1,4-DHP drugs with a well-known antioxidant ability.

PMID- 17446079
TI  - U-ages in soils and groundwater evidencing wet periods 400-600kyr ago in
      southeast Brazil.
AB  - (238)U and its radiogenic daughter (234)U have been utilized for dating soil
      formation and groundwater residence time during the last 1.5 million years, in
      this case based on the U-dissolution/precipitation occurring during modifications
      of the oxidation-reduction conditions. In this paper, we report a 400-600kyr
      proxy of wet periods from sediments occurring in a soil profile developed over
      rocks outcropping at the Parana sedimentary basin in Brazil, and from groundwater
      exploited of Guarani aquifer at the same basin. The approaches indicated
      successful use of the U-modeled ages for suggesting wet periods exceeding the
      past 116-210kyr from previous studies.

PMID- 17446080
TI  - Functional role of mGluR1 and mGluR4 in pilocarpine-induced temporal lobe
      epilepsy.
AB  - Altered expression and distribution of neurotransmitter receptors, including
      metabotropic glutamate receptors (mGluRs), constitute key aspects in
      epileptogenesis, impaired hippocampal excitability and neuronal degeneration.
      mGluR1 mediates predominantly excitatory effects, whereas mGluR4 acts as
      inhibitory presynaptic receptor. Increased hippocampal expression of mGluR1 and
      mGluR4 has been observed in human temporal lobe epilepsy (TLE). In this study, we
      address whether genetic mGluR1 upregulation and mGluR4 knock-down influence
      seizure susceptibility and/or vulnerability of hippocampal neurons by analyzing
      transgenic animals in the pilocarpine TLE model. Therefore, we generated
      transgenic mice expressing mGluR1-enhanced green fluorescent protein (EGFP)
      fusion protein under control of the human cytomegalovirus (CMV) immediate early
      promoter. Status epilepticus (SE) was induced in (a) mice overexpressing mGluR1
      EGFP and (b) mice deficient for mGluR4 (mGluR4 KO) as well as littermate
      controls. In the acute epileptic stage after pilocarpine application, mGluR4 KO
      mice showed a significant increase of severe seizure activity, in contrast to
      mGluR1 transgenics. Analysis of both transgenic mouse lines in the chronic
      epileptic phase, using a telemetric EEG-/video-monitoring system, revealed a
      significant increase in seizure frequency only in mGluR1-EGFP mice. In contrast,
      enhanced neuronal cell loss was only present in the hippocampus of epileptic
      mGluR4 KO mice. Our results suggest a role for mGluR1 in promoting seizure
      susceptibility as well as for mGluR4 to counteract excitatory activity and
      seizure-associated vulnerability of hippocampal neurons. Therefore, our data
      strongly recommend both mGluRs as potential drug targets to interfere with the
      development of hippocampal damage and seizure activity in TLE.

PMID- 17446081
TI  - Evaluation of 188 consecutive homografts implanted in pulmonary position after 20
      years.
AB  - OBJECTIVE: Homografts are considered the gold standard for right ventricular
      outflow tract reconstruction. Their long-term durability is limited, and
      alternatives became available. We evaluate their long-term hemodynamic
      performance to permit comparisons with alternative devices. METHODS: Between 1985
      and 2004, 188 homografts were implanted in pulmonary position at our institution.
      Mean patient age was 24.8 years (range 2 days-75 years); 56 were female and 132
      male. Total follow-up time was 1073 years. Fifty-eight percent were Ross
      procedures (mean age 31.5 years) and 42% were different procedures (mean age 15.6
      years); main diagnoses were tetralogy of Fallot (48%), truncus arteriosus (14%),
      transposition of the great arteries (11%). Twenty-six percent were redo
      implantations. We evaluated freedom from death, explantation, insufficiency,
      relevant gradient, degeneration, and the interval between diagnosis of
      degeneration and therapeutic procedure (therapeutic gap). Results were stratified
      by indication, age, history, homograft size, and origin. RESULTS: Ten-year
      freedom-from explantation was 82% in homografts >19 mm and 45% in smaller ones.
      Ten-year freedom from degeneration was 68% after Ross procedure and 25% after
      other operations; it was 83% in patients older than 10 years at implantation and
      51% in younger ones. 'Non-Ross-procedure' and 'implantation age below 10 years'
      were the only independent risk factors for degeneration. The observed trend
      towards therapeutical gap reduction was not statistically significant.
      CONCLUSIONS: Homograft implantation in the pulmonary position can be performed
      with good long-term freedom from explantation. However, freedom from degeneration
      is a matter of concern. Therefore, alternative valved conduits are required
      especially for pediatric patients.

PMID- 17446083
TI  - Serum levels of interleukin-15 and interleukin-10 and their correlation with
      proliferating cell nuclear antigen in multiple myeloma.
AB  - In order to determine prognostic factors characterizing multiple myeloma (MM)
      cell kinetics, bone marrow proliferative activity and serum Interleukin-10 (IL
      10), and Interleukin-15 (IL-15) levels were measured in 40 newly diagnosed MM
      patients, compared with 10-age and sex-matched-healthy controls. Cell
      proliferation was evaluated by employing a monoclonal antibody directed against
      the proliferating cell nuclear antigen (PCNA), whereas IL-10 and IL-15 were
      measured with quantitative sandwich enzyme immunoassay methods. IL-15, IL-10 and
      PCNA were higher in the patient group than in controls (P<0.001). IL-10 levels,
      and PCNA increased significantly with increasing Durie-Salmon disease stage (I
      III, P<0.002, and P=0.001, respectively). Serum IL-15 levels in MM stage III
      patients were elevated in comparison with stages I and II, the difference
      however, did not reach statistical significance. There was a significant positive
      correlation between serum IL-15 and IL-10 levels (r: 0.372, P<0.01), and between
      serum IL-10 and PCNA (r: 0.608, P<0.0001), as well as a positive correlation of
      serum IL-15 with PCNA, which marginally failed to reach statistical significance.
      Serum IL-15 levels are elevated in MM patients, increase with advancing stage,
      and correlate with Il-10 and PCNA. These proliferative factors may be useful in
      assessing disease progression in MM.

PMID- 17446082
TI  - Aging and the dendritic cell system: implications for cancer.
AB  - The immune system shows a decline in responsiveness to antigens both with aging,
      as well as in the presence of tumors. The malfunction of the immune system with
      age can be attributed to developmental and functional alterations in several cell
      populations. Previous studies have shown defects in humoral responses and
      abnormalities in T cell function in aged individuals, but have not distinguished
      between abnormalities in antigen presentation and intrinsic T cell or B cell
      defects in aged individuals. Dendritic cells (DC) play a pivotal role in
      regulating immune responses by presenting antigens to naive T lymphocytes,
      modulating Th1/Th2/Th3/Treg balance, producing numerous regulatory cytokines and
      chemokines, and modifying survival of immune effectors. DC are receiving
      increased attention due to their involvement in the immunobiology of tolerance
      and autoimmunity, as well as their potential role as biological adjuvants in
      tumor vaccines. Recent advances in the molecular and cell biology of different DC
      populations allow for addressing the issue of DC and aging both in rodents and
      humans. Since DC play a crucial role in initiating and regulating immune
      responses, it is reasonable to hypothesize that they are directly involved in
      altered antitumor immunity in aging. However, the results of studies focusing on
      DC in the elderly are conflicting. The present review summarizes the available
      human and experimental animal data on quantitative and qualitative alterations of
      DC in aging and discusses the potential role of the DC system in the increased
      incidence of cancer in the elderly.

PMID- 17446084
TI  - Structural heterogeneity and environmentally regulated remodeling of Francisella
      tularensis subspecies novicida lipid A characterized by tandem mass spectrometry.
AB  - The structural characterization of environmentally-regulated lipid A derived from
      Francisella tularensis subspecies novicida (Fn) U112 is described using negative
      electrospray ionization with a linear ion trap Fourier transform ion cyclotron
      resonance (IT-FT-ICR) hybrid mass spectrometer. The results indicate that a
      unique profile of lipid A molecular structures are synthesized in response to Fn
      growth at 25 degrees C versus 37 degrees C. Molecular species were found to be
      tetra-acylated, sharing a conserved glucosamine disaccharide backbone, a
      galactosamine-1-phosphate linked to the reducing glucosamine, and multiple O- and
      N-linked fatty acyl groups. Deprotonated molecules were interrogated by MS(n)
      scanning techniques at both high and nominal mass resolution and were found to be
      complex heterogeneous mixtures where structures differed based on the positions
      and identities of the O- and N-linked fatty acyl substituents. For the dominant
      ion series, which consisted of five peaks, 30 unique lipid A structures were
      identified. Estimates for the relative abundance of each structure were derived
      from MS relative abundance ratios and fragment ion ratios from comparable
      dissociation pathways from MS(2) through MS(4) experiments. The results suggest a
      remodeling pathway in which the amide linked fatty acid of the reducing
      glucosamine favors a 3-hydroxyhexadecanoic acid substituent for growth conditions
      at 25 degrees C versus a 3-hydroxyoctadecanoic acid substituent for growth
      conditions at 37 degrees C.

PMID- 17446085
TI  - Mass spectrometric detection of attomole amounts of the prion protein by
      nanoLC/MS/MS.
AB  - Sensitive quantitation of prions in biological samples is an extremely important
      and challenging analytical problem. Prions are the cause of several fatal
      neurodegenerative diseases known as transmissible spongiform encephalopathies
      (TSEs). At this time, there are no methods to diagnose TSEs in live animals or to
      assure a prion-free blood supply for humans. Prions have been shown to be present
      in blood by transfusion experiments, but based on the amount of infectivity found
      in these types of experiments, the amount of misfolded prion protein in blood is
      estimated to be only 30 to 625 amol/mL. More sensitive detection of prions in
      brain would allow earlier detection of disease and assure a safer food supply. We
      studied quantitation of the prion protein by use of nanoscale liquid
      chromatography coupled to a tandem mass spectrometer using the multiple reaction
      monitoring mode of operation. We developed a method based on the detection of
      VVEQMCTTQYQK obtained by reduction, alkylation, and digestion with trypsin of the
      prion protein. Detection of VVEQMCTTQYQK was more sensitive than for the
      derivative with phenylisothiocyanate (PITC) because of decreased ionization
      efficiency of the PITC-derivatized peptides. The VVEQMCTTQYQK method has a LOD of
      20 to 30 amol for pure standards. Proof of principle is demonstrated by
      quantitation of the amount of PrP 27-30 in the brains of terminally ill Syrian
      hamsters.

PMID- 17446086
TI  - Nanomechanical interactions of phenylalanine-glycine nucleoporins studied by
      single molecule force-volume spectroscopy.
AB  - Phenylalanine-glycine (FG)-repeat nucleoporins (Nups) form the major components
      of the selective gating mechanism in the nuclear pore complex (NPC). Hence, a
      primary requirement is to understand how they vacillate between preventing the
      access of passively diffusing molecules and promoting the translocation of
      receptor-bound cargo into the NPC. To shed light on such behavior, we have
      studied the nanomechanical properties of a cysteine-modified FG-rich C-terminal
      domain of hNup153 (i.e., cNup153) and its interactions with importin-beta. This
      is carried out using single molecule force spectroscopy (SMFS) with the atomic
      force microscope (AFM). In the absence of importin-beta, cNup153 is highly
      flexible and can be reversibly stretched and relaxed without any change to its
      intrinsic entropic elasticity, indicating a lack of intra-FG interactions, i.e.,
      natively unfolded. Importin-beta-modified AFM tips reveal complex binding
      topologies with cNup153, and provide evidence for binding promiscuity in FG
      receptor interactions. These differences suggest that cooperativity between FG
      domains arises from FG-receptor interactions instead of FG-FG interactions. On a
      technical note, this work highlights an improved SMFS technique which involves
      pre-passivating the underlying substrate surface with polyethylene glycol to
      reduce undesirable AFM tip-surface effects. A high yield of acceptable data is
      subsequently obtained from the low surface coverage of target molecules by
      implementing SMFS measurements in force-volume (FV) mode.

PMID- 17446087
TI  - Time resolved structure analysis of growing beta-amyloid fibers.
AB  - Formation of beta-amyloid plaques is a crucial feature of Alzheimer's disease. In
      the present work time resolved static light scattering was applied to investigate
      the size and shape of growing beta-amyloid aggregates preceding plaque formation.
      The beta-amyloid protein with 40 amino acid residues was used. Salt free buffer
      solutions and solutions with 0.15M NaCl at 37 degrees C served as the aggregation
      medium. The focus lay on the first 2h following initiation of the aggregation
      process which corresponds to the protofibril phase. Addition of the NaCl
      accelerated the aggregation process considerably. Scattering data from
      aggregation in saline solutions indicated formation of long fibers which suggest
      interpretation of data with the worm-like chain model. Two important results were
      revealed: (i) At the end of the time resolved recordings, the worm-like chain
      model provided a fully adequate picture for the growing aggregates. Chain
      stiffness is characterised in terms of the persistence length, which is close to
      50 nm. The linear mass density of the growing fibers approached a value of two
      monomers per nm corresponding to single stranded fibers, which is in accordance
      with presently existing models for the aggregation of beta-amyloid. The fibers
      finally reached contour lengths of several thousand nanometers. (ii) The plateau
      values for the persistence length and linear mass density observed in the final
      regime are gradually approached from higher values. This observation is
      inconsistent with simple worm-like chains. Rather does it indicate existence of
      another species during the initial phase of the aggregation, in addition to
      monomers and fibers. Aside from further insight into fundamental aspects of beta
      amyloid aggregation, time resolved static light scattering provides an
      appropriate tool for assay tests with drugs designed to interfere with the
      aggregation process.

PMID- 17446088
TI  - Undetected changes in visible stimuli influence subsequent decisions.
AB  - Change blindness-our inability to detect changes in a stimulus-occurs even when
      the change takes place gradually, without any disruption [Simons, D. J.,
      Franconeri, S. L., & Reimer, R. L. (2000). Change blindness in the absence of a
      visual disruption. Perception, 29(10), 1143-1154]. Such gradual changes are more
      difficult to detect than changes that involve a disruption. Using this method,
      David et al. [David, E., Laloyaux, C., Devue, C., & Cleeremans, A. (in press).
      Change blindness to gradual changes in facial expressions. Psychologica Belgica]
      recently showed substantial blindness to changes that involve facial expressions
      of emotion. In this experiment, we show that people who failed to detect any
      change in the displays were (1) nevertheless influenced by the changing
      information in subsequent recognition decisions about which facial expression
      they had seen, and (2) that their confidence in their decisions was lower after
      exposure to changing vs. static displays. The findings therefore support the
      notion that undetected changes that occur in highly salient stimuli may be
      causally efficacious and influence subsequent behavior. Implications concerning
      the nature of the representations associated with undetected changes are
      discussed.

PMID- 17446089
TI  - The case of Dr. Jekyll and Mr. Hyde: a kinematic study on social intention.
AB  - The aim of the present study was to investigate the effects of social intentions
      on action. Participants (N=13) were requested to reach towards, grasp an object,
      and either pass it to another person (social condition) or put it on a concave
      base (single-agent condition). Movements' kinematics was recorded using a three
      dimensional motion analysis system. The results indicate that kinematics is
      sensitive to social intention. Movements performed for the 'social' condition
      were characterized by a kinematic pattern which differed from those obtained for
      the 'single-agent' condition. Results are discussed in terms of a motor
      simulation hypothesis, which assumes that the same mechanisms underlying motor
      intention are sensitive to social intentions.

PMID- 17446091
TI  - Multiple nuclear loci reveal patterns of incomplete lineage sorting and complex
      species history within western mouse lemurs (Microcebus).
AB  - Mouse lemurs (genus Microcebus) are nocturnal primates endemic to the island of
      Madagascar. Until recently, they were classified as two species, one from eastern
      and one from western Madagascar. Previously published analyses of morphometric
      and mitochondrial DNA data show strong support for the recognition of more than
      eight species, however. Here, we test the eight-species hypothesis with DNA data
      derived from four independently segregating nuclear loci. We find many areas of
      congruence between the mitochondrial and nuclear data, but incomplete lineage
      sorting and low mutation rates limit the phylogenetic resolution of the nuclear
      data. Even so, the nuclear loci unanimously find evidence for three deeply
      diverged lineages within the mouse lemur radiation: one that is congruent with
      the mtDNA "southern clade", another that is congruent with the mtDNA "northern
      clade", and one monospecific branch comprised of the species Microcebus
      ravelobensis. The latter result in particular emphasizes the need for careful
      biological study of this species.

PMID- 17446092
TI  - Use of the Precaution Adoption Process Model to examine predictors of
      osteoprotective behavior in epilepsy.
AB  - In the neurology literature it is well established that anti-epileptic drugs
      (AEDs) lead to bone loss (osteopenia and osteoporosis). Several large
      epidemiologic studies have found twice the fracture rate in persons with epilepsy
      compared to the non-epilepsy population. While an increasing level of awareness
      for preventative measures and screening by neurologists and primary care
      physicians are recommended, so far no one has attempted to address how knowledge
      related to calcium and exercise, health beliefs (based on the Health Belief
      Model) and self-efficacy (confidence in abilities) impact osteoprotective
      behaviors in epilepsy, based on the Precaution Adoption Process Model (PAPM). The
      seven-stage PAPM, unlike other health behavior theories where a person is either
      practicing or not practicing the behavior, conceptualizes behavior change as
      dynamic and occurring over time. Validated instruments were used to assess
      knowledge, health beliefs, self-efficacy and stages of the precaution adoption
      process for four osteoprotective behaviors. For dietary calcium; exercise
      knowledge and calcium self-efficacy predicted higher stages of precaution
      adoption. For calcium supplements; age perceived susceptibility for osteoporosis
      and perceived benefits of calcium predicted higher stages. Exercise adoption
      stage was most predicted by exercise knowledge and health motivation. For DEXA
      screening adoption; age and perceived susceptibility predicted higher stages.
      This study provides hints how persons with epilepsy could be influenced to move
      from the unaware/unengaged positions into to the stages of adoption and
      maintenance for osteoprotective behaviors.

PMID- 17446093
TI  - DGGE and 16S rDNA sequencing analysis of bacterial communities in colon content
      and feces of pigs fed whole crop rice.
AB  - The effect of feeding whole crop rice (WCR) to growing-finishing pigs at three
      levels 0 (Control), 10% and 20% on bacterial communities in colon content and
      feces was analyzed using 16S rDNA-based techniques. Amplicons of the V6-V8
      variable regions of bacterial 16S rDNA were analyzed by denaturing gradient gel
      electrophoresis (DGGE), cloning and sequencing. The total number of DGGE bands
      and Shannon index of diversity for feces samples were higher in the pigs fed WCR
      containing diets compared with the control, while a decrease trend was observed
      in these two parameters for colon content samples with the inclusion of WCR in
      the diets, although statistical differences were not significant. In general, the
      intestinal bacterial communities were prone to form the cluster for pig fed the
      same diet. Feeding of WCR induced the presence of special DGGE band with the
      sequence showing 99% similarity to that of Lactobacillus reuteri (DSM 20016T).
      The sequences of seven amplicons in total nine clones showed less than 97%
      similarity with those of previously identified or unidentified bacteria,
      suggesting that most bacteria in gastrointestinal tracts have not been cultured
      or identified. The results suggest that the diet containing WCR did not affect
      the major groups of bacteria, but stimulated the growth of L. reuteri-like
      species.

PMID- 17446094
TI  - Clostridium tertium isolated from gas gangrene wound; misidentified as
      Lactobacillus spp initially due to aerotolerant feature.
AB  - Clostridium tertium has been increasingly reported as a human pathogen. This
      organism is an aerotolerant Gram-positive rod that is often mistaken for other
      organisms, such as Lactobacillus or Bacillus species. We describe a case of a
      patient with a history of intravenous drug use presenting to UCLA-Olive View
      Medical Center with gas gangrene of both upper extremities. The organism was
      initially misidentified as a Lactobacillus species on aerobic culture plates.
      However, terminal spore formation was detected in this isolate on a sub-cultured
      anaerobic culture plate and this isolate was confirmed as C. tertium
      biochemically and genetically by 16S rDNA sequencing. Additional DNA cloning
      libraries made from the formalin-fixed specimen revealed Peptoniphilus species
      and an uncultured Clostridium clone, but not C. tertium. C. tertium might be a
      causative organism of gas-producing myonecrosis but such an association has never
      been described. Clinicians should be aware of the phenomenon of aerotolerance of
      some anaerobes and need to clarify the identification of organisms if the
      clinical picture does not fit the isolated organism.

PMID- 17446095
TI  - Sex determination in the silkworm, Bombyx mori: a female determinant on the W
      chromosome and the sex-determining gene cascade.
AB  - In insects, the sex is determined completely by genetic mechanisms, which at
      least in somatic tissues, are cell autonomous. The sex of the silkworm, Bombyx
      mori, is strongly controlled by the presence of the W chromosome. Genetic studies
      using translocations and deletions of W suggested that a presumptive feminizing
      gene (Fem) is located in a limited region of the W chromosome. Recent genomic
      studies revealed a small number of potential candidates for the Fem gene in this
      region. In addition, a Bombyx homologue of the Drosophila sex determining gene
      doublesex has been identified on an autosome and analyzed. Whereas the Drosophila
      doublesex gene is regulated by activation of splicing in females, the Bombyx
      doublesex gene (Bmdsx) encodes female- and male-specific mRNAs regulated via male
      specific repression of splicing. The vitellogenin gene (Vg) is a target of the
      BmDSX protein, which directly binds to the Vg promoter. Furthermore, as ectopic
      expression of the male-type Bmdsx induces male-like transformation of the sexual
      organs, BmDSX may control sex-specific morphological characteristics in Bombyx.
      This suggests that although upstream events in Drosophila and Bombyx sex
      determination differ, similarities between the two species do exist in downstream
      genetic control of sex determination.

PMID- 17446096
TI  - Response to Pressman: "factors that predispose, prime and precipitate NREM
      parasomnias in adults: clinical and forensic implications" Sleep Med. Rev.
      2007;11:5-9.

PMID- 17446097
TI  - Re-evaluation of the enigmatic species complex Saprolegnia diclina-Saprolegnia
      parasitica based on morphological, physiological and molecular data.
AB  - The phylogenetic relationships among isolates of the Saprolegnia diclina
      Saprolegnia parasitica complex were investigated based on ITS rDNA sequences, and
      correlated with morphological and physiological characters. The isolates studied
      belong to five phylogenetically separate clades. The majority of presumed
      parasitic isolates, mostly isolated from fish lesions, fell within a clade that
      comprises isolates which has been variously named as S. diclina Type 1, S.
      parasitica, Saprolegnia salmonis or just as unnamed Saprolegnia sp. Presence of
      bundles of long-hooked hairs on secondary cysts, high frequency of retracted
      germination, and oogonia production at 7 degrees C (when occurring) were
      characteristic of this clade. A single isolate identified as S. diclina Type 2
      clustered in a clade along with Saprolegnia ferax isolates. The isolates
      identified as S. diclina s. str. (S. diclina Type 3) distributed in two clades
      and appeared closely related to Saprolegnia multispora and to a number of Chilean
      isolates identified as Saprolegnia australis. The ITS sequences of clade I were
      almost identical even though the isolates were of diverse geographical origins
      and showed physiological and morphological differences and variations in their
      pathogenicity. This suggest these species reproduces clonally even in apparently
      sexually competent isolates. Adaptation to parasitism in Saprolegnia might have
      occurred at spore level by the development of long-hooked hairs to facilitate
      host attachment and selection of a retracting germination. The use of the name S.
      parasitica should be assigned to isolates of clade I that contained isolates
      forming cysts with bundles of long-hooked hairs.

PMID- 17446098
TI  - Telomerase: A missing link between ageing, cancer and novel therapies?

PMID- 17446099
TI  - Inflammation and response to steroid treatment in limb-girdle muscular dystrophy
      2I.
AB  - Limb-girdle muscular dystrophy (LGMD) type 2I, caused by mutations in the fukutin
      related protein gene (FKRP), is one of the most common forms of LGMD in
      childhood. We describe two patients with LGMD2I and a Duchenne-like phenotype. In
      addition to the common L276I mutation, both patients had a new mutation in FKRP,
      L169P and P89L, respectively. Clinical onset was triggered by viral upper
      respiratory tract infections. In addition to the common dystrophic pattern with a
      weak immune histochemical staining for alpha-dystroglycan, muscle biopsy showed
      inflammatory changes. This was especially striking in one of the patients with up
      regulation of MHC class 1 antigen, suggestive of myositis. Both patients showed a
      good clinical response to treatment with prednisolone, which was initiated at
      daily dosage of 0.35 mg/kg/day. Our results provide evidence for an inflammatory
      involvement in the pathological expression of LGMD2I and open up the possibility
      that this disorder could be treatable with corticosteroids.

PMID- 17446100
TI  - Dysynchiria is not a common feature of neuropathic pain.
AB  - Patients with chronic neuropathic pain (non-CRPS) and brush-evoked allodynia
      watched a reflected image of their corresponding but opposite skin region being
      brushed in a mirror. Unlike complex regional pain syndrome Type 1, this process
      did not evoke any sensation at the affected area ('dysynchiria'). We conclude
      that central nociceptive sensitisation alone is not sufficient to cause
      dysynchiria in neuropathic pain. The results imply a difference in cortical pain
      processing between complex regional pain syndrome and other chronic neuropathic
      pain.

PMID- 17446101
TI  - Conjunctival granuloma caused by surgical talc.
AB  - Talc from surgical gloves has been known to be a cause of granulomas within the
      surgical cavity. We report a case in which recurrent conjuntival inflammation was
      found to be caused by talc.

PMID- 17446102
TI  - Osteochondroma of the trochlea presenting as acquired Brown syndrome: a case
      report.
AB  - The following is a rare observational case report of a 16-year-old boy who
      presented with acquired Brown syndrome associated with a painless slowly growing
      mass in the supranasal area of the left eye. Meticulous surgical removal of the
      mass resulted in recovery of superior oblique muscle function. Histopathology was
      consistent with osteochondroma of the trochlea. To the knowledge of the authors,
      this is the first reported case of osteochondroma of the trochlea causing
      acquired Brown syndrome.

PMID- 17446103
TI  - Accommodative ability in exotropia: predictive value of surgical success.
AB  - PURPOSE: To evaluate the state and symmetry of accommodative response in the two
      eyes of patients with basic intermittent exotropia and to determine whether
      accommodative response is a predicting factor to the outcome of unilateral
      recession-resection procedures or symmetric lateral rectus recessions. METHODS:
      Dynamic retinoscopy was performed preoperatively on 47 patients with basic
      intermittent exotropia with the capacity for fusion who were undergoing a first
      operation for intermittent exotropia. To obtain a clinical measurement of the
      degree of binocular accommodative response, the monocular estimate method was
      used. Patients were divided into two groups: those with an "equal effective
      accommodative response" and those with an "unequal accommodative response"
      between the two eyes. Both groups received either unilateral recession-resection
      procedures or symmetric lateral rectus recessions. RESULTS: Thirty-two of 47
      patients (68%) showed a persistent interocular difference in accommodative
      amplitude (asymmetric accommodation) of at least 0.75 D. Among these 32 patients
      with an "unequal effective accommodation," 5 of 14 patients (35.7%) receiving
      lateral rectus recessions had a satisfactory outcome compared with 13 of the 18
      patients (72%) receiving recess/resect procedures (p = 0.039). Of the 15 patients
      with an "equal effective accommodation," 7 of 8 (87%) receiving recession
      resection procedures had a satisfactory outcome compared with 5 of 7 patients
      (71%) who had lateral rectus recessions (p = 0.57). CONCLUSIONS: Data suggest
      that patients with an asymmetric accommodative response benefit more from
      recession-resection procedures. A decrease in accommodative response of the
      nondominant eye could be a predicting factor on the outcome of exotropia surgery.

PMID- 17446104
TI  - Traumatic globe luxation in a 6-year-old girl playing with a tube of wrapping
      paper.
AB  - A 6-year-old girl was playing by herself with a tube of gift wrap just before the
      winter holidays. In a panic, she came upstairs from the den with a protruding
      right eye. When used as a make-believe telescope, the tube of wrapping paper was
      the perfect diameter to fit within the orbit's bony limits and around the globe.
      A small force to the tip of the tube held up to the eye was sufficient to propel
      the eyelids backward while luxating the globe forward. Visual acuity in the eye
      deteriorated within 2 hours but the vision loss was reversed entirely with prompt
      reduction under general anesthesia. While not intended as such, the gift-wrap
      tube has long been a popular play instrument for children around the holidays.
      This case illustrates the risk of luxating an eye with a gift-wrap tube and the
      benefits of prompt reduction of a traumatically luxated globe with traumatic
      optic neuropathy.

PMID- 17446106
TI  - Structural investigation of PAP derivatives by CoMFA and CoMSIA reveals novel
      insight towards inhibition of Bcr-Abl oncoprotein.
AB  - Molecular modeling by 3D-QSAR comparative molecular field analysis (CoMFA) and
      comparative molecular similarity indices analysis (CoMSIA) were employed on a
      series of phenylaminopyrimidine-based (PAP) Bcr-Abl inhibitors. The chemical
      structures of 63 PAP analogues were aligned using a template extracted from the
      crystal structure of STI571 bound to Abl kinase. Subsequently, the structures
      built were divided into training and test sets that include 53 and 10 compounds,
      respectively. Statistical results showed that the 3D-QSAR models generated from
      CoMSIA were superior to CoMFA (CoMSIA; q2=0.66, r2=0.94, N=3, F=139.09,
      r2pred=0.64 while CoMFA; q2=0.53, r2=0.73, N=3, F=43.53, r2pred=0.61). Based on
      the contour interpretation, the attachment of hydrophobic and bulky groups to the
      phenyl and pyrrolidine (D- and E-ring of NS-187, respectively) along with highly
      electronegative groups around the D-ring are important structural features for
      the design of second-generation Bcr-Abl inhibitors. The generated models are
      predictive based on reproducible values of the predicted compared with
      experimental activities in the test set. Further, the complementary analysis of
      contour maps to the Bcr-Abl binding site suggested the anchor points for binding
      affinity.

PMID- 17446107
TI  - Prevalence of Tritrichomonas foetus infection in cats with diarrhoea in the UK.
AB  - Faecal samples from 111 cats with diarrhoea that were living in the UK were
      submitted for the assessment of Tritrichomonas foetus infection by polymerase
      chain reaction (PCR). Sixteen (14.4%) samples were found to be positive. In
      agreement with studies from the USA, infected cats were predominantly of a year
      of age or less and of a pedigree breed, with Siamese and Bengal cats specifically
      over-represented in this population.

PMID- 17446108
TI  - Correlates for disease progression and prognosis during concurrent HIV/TB
      infection.
AB  - Mycobacterium tuberculosis (Mtb) and the human immunodeficiency virus (HIV) are
      both life-threatening pathogens in their own right, but their synergic effects on
      the immune system during co-infection markedly enhance their effect on the host.
      This review focuses on the bidirectional interaction between HIV and Mtb and
      discusses the relevance of sputum smear examination, CD4+ counts, viral load at
      baseline and after initiation of anti-retroviral therapy, as well as additional
      existing and new potential immune correlates of disease progression and
      prognosis. These markers include beta2-microglobulin, neopterin, tumor necrosis
      factor receptor II (TNFRII), CD8+/CD38+, soluble urokinase plasminogen activator
      receptor (suPAR) and CXCL10 (or IP-10).

PMID- 17446109
TI  - [Ovary tumor in chronic myeloid leukaemia. Case report].
AB  - Granulocytic sarcoma or chloroma is a neoplasia consisting of myeloid precursors
      in an extramedullary site. Its appearance in chronic myeloid leukaemia is
      unusual. We report a case of ovary tumor associated with chronic myeloid
      leukaemia in chronic phase.

PMID- 17446110
TI  - [Indications of MRI in the initial local staging of early-stage breast cancer].
AB  - MR Imaging is the most sensitive technique for detecting breast cancer. In
      patients with breast cancer, the additional value of MRI is validated in patients
      candidates for a breast-conserving surgery and when: cancer is occult, size
      evaluation is difficult at standard imaging, parietal involvement is suspected,
      and before neoadjuvant chemotherapy. In fatty breasts, MRI is not routinely
      recommended, because of same performances as in standard imaging. In dense
      breasts, MRI becomes significantly more sensitive than mammography for detecting
      multifocality and multicentricity with a positive predictive value of 60% for
      detected additional foci. Thus, a decision of mastectomy should not be made
      solely on the basis of MRI and may require additional tissue sampling of areas of
      concern identified by breast MRI. The additional value of breast MRI is
      particularly useful in patients with dense breasts and high risk factors for
      local recurrence: young age (< 40 years), familial high risk, or because of a
      high-grade invasive cancer greater than 2 cm in size. Performing breast MRI in
      such patients underlies requirements: an expert breast imaging team, optimal MRI
      protocols, and radiologists working in concert with the multidisciplinary
      treatment team.

PMID- 17446111
TI  - [Laparoscopic repair of an incomplete post obstetrical uterine rupture. About one
      case].
AB  - The rate of incomplete uterine ruptures is unknown. These ruptures are usually
      asymptomatic but may cause chronic pelvic pain and/or intermenstrual bleeding.
      The conservative surgical repair techniques described in the literature are often
      practised by vaginal, combined (vaginal and laparoscopic) or hysteroscopic way.
      We propose an exclusive laparoscopic repair technique with satisfactory
      anatomical and functional short-term results.

PMID- 17446113
TI  - Sono-synthesis of imidazolidine-2-thione as a base compound of some
      pharmaceutical products.
AB  - This work describes the results of investigations carried out to investigate the
      synthesis of imidazolidine-2-thione as a heterocyclic compound in the presence of
      ultrasound (sono-synthesis) and in the absence of ultrasound (conventional
      method). Instead of reflux in the conventional method, the mixture was sonicated
      indirectly in sono-synthetic method with 500 kHz at different temperatures. Some
      experiments were also carried out without catalyst with 500 and 900 kHz. In the
      conventional method, the yield of the reaction was increased by increasing the
      temperature but in sono-synthetic method, the thermal dependence was different in
      the range of temperature studied (10-50 degrees C). In the presence of
      ultrasound, the yield was reached to more than 93% after 1h but in the
      conventional method it reached only 27% under the same conditions. Comparison was
      carried out with and without catalyst. It is also possible to achieve a high
      yield of product under sonication without the use of a catalyst.

PMID- 17446114
TI  - A measurement technique to evaluate the macroscopic permeability of the vertebral
      end-plate.
AB  - The remodelling response of vertebral segments in idiopathic scoliosis or disc
      degeneration, shows a modification of the disc hydration. The investigation of
      mass transport between the disc and the vertebral body is relevant to
      understanding the normal and pathological behaviour of the spine. The measurement
      method we adopted, to derive the macroscopic permeability of the vertebral end
      plate, used the relaxation pressure due to a transient-flow rate into the
      biological structure. Our approach mimicked the in vivo conditions of mass
      transfer between the disc and the vertebral bodies. It minimized the flow-induced
      matrix compaction and it allowed the boundary conditions of the specimen to be
      controlled. We proposed a specific theoretical method and an associated device
      according to poroelastic theory. A preliminary evaluation with a controlled
      porous medium, preceded a pilot study in an animal model (lumbar L(4)-L(5)
      segment of a 4 months old female pig). The macroscopic permeability of
      multilayered cylindrical specimens including the trabecular bone, subchondral
      bone and cartilage end-plate was measured, using a 'cartilage-towards-bone' fluid
      flow direction. A histologic evaluation completed the biomechanical approach.
      Results showed that the central zone was more permeable than the periphery and
      this concurred with qualitative studies from the literature.

PMID- 17446115
TI  - The human corneal endothelium: new insights into electrophysiology and ion
      channels.
AB  - The corneal endothelium is a monolayer that mediates the flux of solutes and
      water across the posterior corneal surface. Thereby, it plays an essential role
      to maintain the transparency of the cornea. Unlike the epithelium, the human
      endothelium is an amitotic cell layer with a critical cell density and the risk
      of corneal decompensation. The number of endothelial cells subsequently decreases
      with age. Moreover, the endothelial cell loss is accelerated after various
      impairments such as surgical trauma (e.g. cataract extraction) and following
      corneal transplantation. This cell loss is associated with programmed cell death
      (apoptosis) and changed ion channel activity. However, little is known about the
      electrophysiology and ion channel expression (in particular Ca2+ channels) in
      corneal endothelial cells. This article reviews our current knowledge about the
      electrophysiology of the corneal endothelium. It highlights ion channel
      expression, which may have a major role in corneal cell physiology and
      pathological events. A better understanding of the (electro)physiological
      function of the cornea may lead to the development of clinical relevant new
      therapeutic and preventive measures.

PMID- 17446117
TI  - Druggability of human disease genes.
AB  - The availability of complete genome sequences and the wealth of large-scale
      biological datasets provide an unprecedented opportunity to elucidate the genetic
      basis of human diseases. Here we use integrative in silico approaches to provide
      an accurate description of gene functions to a set of 1737 highly curated disease
      genes in the human genome. This analysis is the first attempt on in silico
      identification of druggable domains within disease genes. We provide information
      on gene architecture and function, druggability in the context of available
      drugs, and evolutionary conservation across 38 model eukaryotic genomes. These
      data could serve as a useful compendium for integrated information on disease
      genes with the potential for exploring pharmaceutically exploitable targets. Our
      analyses underscore the utility of large genomic databases for in silico
      systematic drug target identification in the post-genomic era.

PMID- 17446116
TI  - Dopamine replacement therapy does not restore the ability of Parkinsonian
      patients to make rapid adjustments in motor strategies according to changing
      sensorimotor contexts.
AB  - The ability of dopamine replacement to restore rapid motor adjustments in
      Parkinson's disease (PD) was investigated. Medicated and non-medicated patients
      performed finger-to-nose movements while simultaneously bending the trunk
      forward, without vision. Trunk motion was blocked unexpectedly, necessitating
      rapid adjustments in arm trajectories. Patients exhibited irregular hand paths,
      plateaus in hand velocity, and prolonged movement times, which were significantly
      greater in perturbed trials. Medication improved kinematics but perturbation
      induced disturbances persisted and did not approximate the levels of non
      perturbed trials nor those of controls. Dopaminergic replenishment in PD may
      therefore have limited restorative benefits for rapid context-specific motor
      control.

PMID- 17446118
TI  - Structured to reduce the mitogenicity of anti-CD3 antibody based on computer
      guided molecular design.
AB  - The mouse anti-human CD3 monoclonal antibody such as OKT3 is a potent
      immunosuppressive agent used in clinical transplantation to manipulate T-cell
      functions and prevent acute allograft rejection. However, the broad use of anti
      CD3 antibody in clinical treatment was severely limited by the side effects of
      human anti-mouse antibody response and cytokine release syndrome. In this study,
      on the basis of a murine anti-human CD3 antibody yCD3 obtained in our previous
      work, a novel engineered anti-human CD3 antibody fragment (i.e. V(H)-Linker-V(L)
      Hinge-CH(3)) was constructed with computer-guided molecular design method to
      avoid the clinical side effects. According to the distance geometry and intra
      molecular interaction, the hinge region was re-designed and different from the
      parental hinge region in human IgG1. With the novel hinge region, the cysteine
      residues in hinge were exposure and prone to form the disulfide bond. Therefore,
      a novel bivalent antibody fragment named as mini-yCD3 was obtained. Mini-yCD3
      displayed similar antigen-binding affinity and specificity to yCD3. Importantly,
      mini-yCD3 was shown to be much less potent in the induction of T-cell
      proliferation, cytokine release (interferon-gamma and interleukin-2) and early
      activation marker expression on the cell surface (CD69 and CD25) than parental
      yCD3. Furthermore, mini-yCD3 was effective in modulating T-cell receptor/CD3 and
      inhibiting mixed lymphocyte reaction with similarity as yCD3. In conclusion, the
      constructed mini-yCD3 was much less mitogenic to T cells but retained potent
      immunosuppression, suggesting it might be an alternative to yCD3 as an
      immunosuppressive drug with less immunogenicity and toxicity for clinical
      application.

PMID- 17446119
TI  - Evaluation of an automated in vitro micronucleus assay in CHO-K1 cells.
AB  - In this paper, we describe the evaluation of an automated in vitro micronucleus
      assay using CHO-K1 cells in 96-well plates. CHO-K1 cells were pre-loaded with a
      cell dye that stains the cytoplasm, after which the cells were treated with the
      test compounds for either 3h (for the +S9 condition) or 24h (for the -S9
      condition). A total of 10 concentrations were tested, of which the top five
      concentrations were scored (limited by either cytotoxicity or solubility). At the
      end of the incubation period the cells were fixed and their DNA was stained with
      Hoechst. The visualization and scoring of the cells was done using an automated
      fluorescent microscope coupled with proprietary automated image analysis software
      provided by Cellomics (Pittsburg, PA). A total of 46 compounds were used in this
      evaluation, including 8 aneugens and 25 clastogens with varied mechanisms of
      action. Thirteen non-genotoxic compounds were also included. The automated
      scoring had a sensitivity of 88% and a specificity of 100%, with a predictive
      value positive of 100% and a predictive value negative of 76%, compared to data
      from the literature that was obtained with manual scoring. We also describe the
      incorporation of a metabolic activation system using rat liver S9 homogenates,
      and the use of cell number counts as a cytotoxicity index which is complementary
      to the CBPI- (cytokinesis-block proliferation index) based index. Finally, we
      also discuss the potential for artefactual findings due to fluorescent
      precipitate, which should be carefully monitored to prevent false positive
      results. In conclusion, the automated in vitro micronucleus scoring is a valid
      alternative to the manual scoring of slides, and it has the advantage of
      generating data in a rapid and consistent manner, and with low compound
      requirements, which makes it well suited as a screening assay in the early stages
      of compound development.

PMID- 17446120
TI  - Synthesis and infrared and fluorescent spectra of rare earth complexes with a new
      amide ligand.
AB  - Solid complexes of rare earth nitrates and picrates with a new amide ligand, 1,6
      bis[(2'-benzylaminoformyl)phenoxyl]hexane (L) have been prepared. These complexes
      are characterized by elemental analysis, UV-vis spectra and IR spectra. The
      fluorescent and luminescent properties of the Eu(III) and Tb(III) nitrates and
      picrates complexes in solid state are also investigated. Under the excitation of
      UV light, these complexes except Tb(III) picrate complex exhibit characteristic
      emission of europium and terbium ions. The influence of the counter anion on the
      fluorescent intensity is also discussed.

PMID- 17446121
TI  - Progress and prioritizing needs for future research on testate amoebae: a meeting
      report on the International Symposium on Testate Amoebae, Antwerp, Belgium,
      September 12-14, 2006.

PMID- 17446122
TI  - Management of life-threatening subcutaneous emphysema using subcutaneous penrose
      drains and colostomy bags.
AB  - Subcutaneous emphysema is a common complication post cardiothoracic surgery.
      Severe subcutaneous emphysema may cause respiratory obstruction and sometimes
      tracheostomy or intubation is required. We report a case of massive subcutaneous
      emphysema following aortic valve replacement. It was not relieved with initial
      bilateral chest tubes, but the subcutaneous Penrose drains produced a dramatic
      improvement and provided effective decompression of the subcutaneous emphysema.
      We also describe the colostomy bags, which covered the drains. These were useful
      for keeping the area sterile and measuring the amount of air through the
      individual drains.

PMID- 17446123
TI  - Thrombosis and thrombolysis: platelet membrane glycoproteins.
AB  - Over the last quarter of a century, therapy for acute coronary syndromes has
      rapidly evolved. The major causative factor for acute coronary syndromes,
      particularly acute myocardial infarction, is now recognised to be coronary
      thrombosis and therapies using thrombolytic agents to dissolve thrombus or
      percutaneous coronary interventions (angioplasty and stenting) to mechanically
      disrupt thrombus and restore vessel patency are now routine. The precipitant for
      coronary thrombus is believed to be atherosclerotic plaque rupture. Plaque
      rupture has been demonstrated at autopsy in humans and in vivo in an experimental
      animal model for atherosclerosis. Thrombus formed at these sites is platelet rich
      and anti-platelet therapy has an established role in the treatment of
      cardiovascular disease. The study of platelet membrane glycoproteins, which
      mediate platelet adhesion and aggregation, has resulted in specific therapies.
      Future directions for research with clinical relevance include the development of
      markers for plaque instability.

PMID- 17446124
TI  - Development of device therapy for ventricular arrhythmias.
AB  - The past 25 years have seen the implantable cardioverter defibrillator emerge as
      the treatment of choice for ventricular arrhythmias with reduction in size but
      increased therapeutic options. Understanding the complex mechanisms of
      ventricular arrhythmias and defibrillation in normal and diseased hearts has been
      the focus of many research teams including that of John Uther at the Westmead
      Hospital Department of Cardiology. Marked improvements in capacitor and battery
      technologies, arrhythmia discrimination, pacing algorithms, shock waveforms and
      monitoring capabilities enable wider use and patient acceptance. Emergence of
      cardiac resynchronisation therapy and the implantable defibrillator for treatment
      of chronic heart failure is not only giving quality of life and extended survival
      for heart failure patients but has also cast new light on the evolution of heart
      failure.

PMID- 17446125
TI  - Special issue: John Uther Festschrift.

PMID- 17446126
TI  - Therapeutic prospects of cardiac gene transfer.
AB  - Cardiovascular diseases remain a major cause of morbidity and mortality. Despite
      significant gains in medical and surgical treatment of these conditions, the
      burden imposed continues to increase, particularly as the population ages. Hence,
      there exists an impetus to explore novel therapeutic approaches. Gene therapy,
      broadly defined as the use of nucleic acid sequences as medicine, is an example
      of such a novel approach. The potential of gene therapy has been explored in
      several models of both inherited monogenic and acquired polygenic cardiovascular
      diseases, such as heart failure and arrhythmia. Exciting developments in gene
      transfer technology and important insights into the molecular basis of these
      common diseases have placed them within reach of gene-based therapy.

PMID- 17446127
TI  - Chest-wall metastasis in a patient who underwent liver transplantation due to
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma is a common malignancy. It may cause extrahepatic
      metastases through haematogenous or lymphatic dissemination or direct invasion.
      Furthermore, methods such as fine-needle aspiration biopsies performed to obtain
      a diagnosis or percutaneous ethanol injection and radiofrequency hyperthermia
      performed for treatment may also cause tumour dissemination. We present a 52-year
      old male patient whose isolated right chest wall metastasis developed after liver
      transplantation due to hepatocellular carcinoma. We performed chest wall
      reconstruction after the mass was removed.

PMID- 17446128
TI  - Surgery and ablative therapy for ventricular tachycardia.
AB  - In the absence of acute ischaemia, ventricular tachycardia (VT) is the most
      common arrhythmia leading to cardiac arrest and death. This paper will describe
      the history of research into VT and the therapies that evolved. The contributions
      of John Uther and other members of the Department of Cardiology at Westmead
      Hospital will be outlined and placed into perspective.

PMID- 17446129
TI  - Operative and percutaneous procedures for cure of atrial fibrillation.
AB  - The surgical maze procedure was the first successful curative procedure for
      atrial fibrillation. However it is a technically difficult procedure and has not
      been widely adopted. Subsequently, radiofrequency ablation has been used to
      replace the surgical incisions of the maze operation in new open-heart and
      percutaneous catheter based procedures. These procedures have an acceptable level
      of efficacy and safety, and should be considered for patients with problematic
      atrial fibrillation. This review summarises the development of these procedures,
      their current role in the treatment of atrial fibrillation, patient selection and
      after care.

PMID- 17446130
TI  - Assessment, significance and mechanism of ventricular electrical instability
      after myocardial infarction.
AB  - The mechanism of reentrant tachycardia was established nearly a century ago, but
      the relationships between myocardial infarction and predisposition to sudden
      death were not unravelled until much later. In the latter half of the twentieth
      century many studies sought to ascertain what variables were predictive of death
      following myocardial infarction. Approximately one half of all deaths during the
      year following myocardial infarction are sudden and due to ventricular
      tachycardia (VT) or ventricular fibrillation (VF). We aimed to utilise non
      invasive signal-averaging, along with programmed electrical stimulation of the
      heart, to determine whether one could predict spontaneous ventricular tachycardia
      and sudden death late after myocardial infarction. The sensitivity of ventricular
      electrical instablility (inducible ventricular tachycardia or fibrillation) as a
      predictor of instantaneous death or spontaneous VT was 86%, and the specificity
      was 83%. When other variables (delayed ventricular activation at signal
      averaging, ejection fraction at gated heart pool scan, ventricular ectopic
      activity at ambulatory monitoring and exercise testing) were taken into account,
      inducible VT at electrophysiological study was the single best predictor of
      spontaneous VT and sudden cardiac death after myocardial infarction. The Westmead
      studies of Uther et al. in the decade or so from 1980 established programmed
      stimulation as the best predictor of sudden death after myocardial infarction.
      Subsequent studies by others have demonstrated a survival advantage of
      defibrillator implantation in patients with low ejection fraction (and inducible
      ventricular tachycardia) after myocardial infarction.

PMID- 17446131
TI  - Late drug-eluting stent thrombosis and erythropoietin: cause and effect?
AB  - A case of late thrombosis of a sirolimus-eluting stent, 16 months after
      implantation, is described. Two weeks prior to presentation with stent thrombosis
      the patient had a 50% dose increase of longterm erythropoietin. The prothrombotic
      effect of erythropoietin may have precipitated the thrombotic event.

PMID- 17446132
TI  - Giant cardiac myxoma.
AB  - Although cardiac myxomas remain an uncommon group of malignancies, they are the
      most common form of primary cardiac tumour. Clinical presentations can be varied
      with local cardiac haemodynamic consequences, valvular insufficiency or even
      embolic phenomena. We present a case of a 46-year-old man with chronic abdominal
      pain and discuss a number of diagnostic challenges that were confronted up until
      a definitive diagnosis of cardiac myxoma was made. The resultant outcome was
      excellent with the patient achieving complete recovery from long term disabling
      symptoms.

PMID- 17446133
TI  - Transjugular intrahepatic portosystemic shunt prior to cardiac surgery with
      cardiopulmonary bypass in patients with cirrhosis and portal hypertension.
AB  - Because of the increased complications associated with cardiac surgery in
      patients with cirrhosis and portal hypertension, various preoperative
      preparations have been utilised. In order to reduce the bleeding risk by
      decompressing portosystemic collaterals and to correct the fluid shift, we
      performed transjugular intrahepatic portosystemic shunt (TIPS) in two patients
      with cirrhosis and portal hypertension prior to major cardiac surgery with
      cardiopulmonary bypass. Both patients had satisfactory surgical outcome with no
      bleeding complications. One patient developed hepatic encephalopathy which was
      managed medically. We believe that preoperative TIPS benefits the patient with
      cirrhosis and portal hypertension undergoing cardiac surgery by decreasing the
      major surgical complications through improvement of fluid imbalance and reduction
      of the bleeding risk. Because of the risks of TIPS, such as encephalopathy and
      liver failure, preoperative TIPS placement must be reserved for patients with
      fluid shift or high risk criteria of bleeding.

PMID- 17446134
TI  - Do cancer patients always want to talk about difficult emotions? A qualitative
      study of cancer inpatients communication needs.
AB  - The aim of this study was to find out, through qualitative in depth interviews,
      if cancer patients in an Oncology ward always want to talk about their feelings
      and difficult emotions regarding the disease and their future while they are
      inpatients, and if not, to identify the reasons why. People with cancer often
      face emotional and spiritual distress, but try to cope with their life situation
      optimally. It is therefore important to determine their communication needs when
      they are inpatients. Giorgi's approach to phenomenology was used as research
      method. Twenty inpatients with various cancer diagnoses in different stages and
      with different prognoses were interviewed. The findings revealed that cancer
      patients did not always want to talk to the nurses about their difficult feelings
      regarding the future when they were inpatients in an Oncology ward. The main
      themes identified why were: cognitive avoidance and distancing; normalization,
      finding meaning and living in the present, and support from family and friends.
      The patients wanted to talk about normal life, their hobbies and their families.
      This conversation seemed to support their coping strategies by helping them to
      find meaning and hope, and must be recognized as important aspects of spiritual
      and emotional care.

PMID- 17446135
TI  - Adenovirus infections and lung disease.
AB  - Adenovirus, particularly its E1A protein, has been investigated in the
      pathogenesis of chronic obstructive pulmonary disease (COPD). High levels of E1A
      DNA were found in the lungs of COPD patients, where its expression increased with
      disease severity. In lung epithelial cells, E1A increased intercellular adhesion
      molecule-1 and interleukin-8 expression, as well as nuclear factor-kappaB
      activation, in response to inflammatory stimuli. In addition to regulating the
      mediators that promote emphysema, E1A upregulates transforming growth factor
      beta1 expression in bronchiolar epithelial cells and transforms lung epithelial
      cells to express mesenchymal markers. These results support its additional role
      in the airway remodeling process reported in COPD.

PMID- 17446136
TI  - Therapeutic apheresis for myositises.
AB  - The inflammatory myopathies, commonly described as idiopathic, are the largest
      group of acquired and potentially treatable myopathies. Dermatomyositis and
      polymyositis are generally responsive to immunosuppressive therapies, but could
      be refractory to them. Therapeutic plasma exchanges (TPE) have been used for
      three decades to treat autoimmune diseases. Their mechanism of action, which
      hinges on profound modulation of the immune system, is only partially understood.
      Despite the absence of supportive evidence provided by controlled trials, some
      observations suggest that TPE could have a role to play in the therapeutic
      strategy for refractory inflammatory myopathies, especially acute forms. TPE
      should probably be indicated preferentially for refractory and acute inflammatory
      myopathies, in combination with immunosuppression and/or anti-B-lymphocyte
      therapy.

PMID- 17446138
TI  - Preterm labour. Myometrial function in prematurity.
AB  - The primary function of the uterus during gestation is to harbour the growing
      conceptus in a largely quiescent environment. Upon maturation of the fetus to a
      point sufficient for extrauterine survival, the uterus must remodel itself
      sufficiently to generate forceful contractions during labour. During preterm
      delivery, the process of remodelling of the myometrium occurs early due to a
      number of different causes, although the underlying basis for myometrial
      contraction remains the same. This review summarises the anatomical,
      physiological and molecular basis for contraction. We describe the fibre
      structure of the human uterus and how this relates to the spread of electrical
      excitation during a contraction. The process of excitation within a single
      myometrial cell is described, as well as how this relates to contraction. We then
      focus on how excitation-contraction coupling is modulated by intercellular
      communication, pharmacomechanical-coupling and hormonal milieu. Lastly, we
      consider the actions of the commonly accepted uterine agonists oxytocin,
      prostaglandin F(2alpha), and prostaglandin E(2), and the tocolytic ritodrine.

PMID- 17446137
TI  - A novel method for KIR-ligand typing by pyrosequencing to predict NK cell
      alloreactivity.
AB  - Studies have shown that KIR-ligand mismatching to predict NK cell alloreactivity
      may result in less relapse and better survival in patients with AML. KIR-ligands
      are distinguished by single nucleotide polymorphisms (SNPs) from HLA-B and HLA-C
      sequences. We hypothesized that pyrosequencing to determine KIR-ligand status by
      direct sequencing of the ligand epitope can be done as an alternative to high
      resolution HLA-typing. Pyrosequencing is rapid and would be particularly useful
      in analysis of retrospective cohorts where high-resolution HLA-typing is
      unavailable or too expensive. To validate this assay, RNA and DNA from 70
      clinical samples were tested for KIR-ligand by pyrosequencing. Primer binding to
      invariant regions without known SNPs was critical for KIR-ligand assignment by
      pyrosequencing to be in full concordance with high-resolution HLA-typing.
      Pyrosequencing is sensitive, specific, high-throughput, inexpensive, and can
      rapidly screen KIR-ligand status to evaluate potential alloreactive NK cell or
      transplant donors.

PMID- 17446139
TI  - Evaluation of global left ventricular function and mechanical dyssynchrony in
      patients with an asymptomatic left bundle branch block: a real-time 3D
      echocardiography study.
AB  - BACKGROUND: A left bundle branch block (LBBB) affects both global left
      ventricular (LV) function and mechanical dyssynchrony. The aim was to evaluate
      global LV function and mechanical dyssynchrony with real-time 3D echocardiography
      (RT3DE), in asymptomatic LBBB patients, healthy volunteers and patients with
      symptomatic heart failure (HF) and a LBBB. Furthermore, the relation between
      presence or absence of symptoms of HF and mechanical dyssynchrony was
      investigated. METHODS: RT3DE was performed in 61 consecutive patients: 16 healthy
      volunteers, 22 patients with an asymptomatic LBBB and 23 patients with
      symptomatic HF and a LBBB. Global LV function and the systolic dyssynchrony index
      (SDI) were measured. RESULTS: In healthy volunteers, mean LV ejection fraction
      was 54 +/- 5%, in asymptomatic LBBB patients 50 +/- 9%, and in HF patients 29 +/-
      9%. SDI was 5.6 +/- 3.6%, 7.3 +/- 3.2% and 12.8 +/- 4.8% for healthy volunteers,
      asymptomatic LBBB patients and HF patients respectively. SDI differed
      significantly between HF patients and both other groups. A cut-off value for SDI
      for presence of symptoms of HF was 10.8%. CONCLUSION: Asymptomatic LBBB patients
      have more depressed global LV function than healthy volunteers have; patients
      with symptoms of HF and a LBBB have severe global LV dysfunction. Asymptomatic
      LBBB patients have an intermediate mechanical dyssynchrony; HF patients with a
      LBBB have the most severe mechanical dyssynchrony. A substantial amount of
      mechanical dyssynchrony might be accompanied by the presence of symptoms of HF.

PMID- 17446140
TI  - Epilepsy in Laos: knowledge, attitudes, and practices in the community.
AB  - OBJECTIVE: We evaluated beliefs about, attitudes toward, and stigma associated
      with epilepsy in four districts of central Laos. METHOD: For this study, 83
      people with epilepsy, 83 family members, and 166 matched villagers in Vientiane
      Province were interviewed. RESULTS: From patients to families to villagers, there
      existed a significantly increasing gradient of misbeliefs. Dubbed locally as "mad
      pig disease," epilepsy was viewed as having a supernatural origin by 25-42% of
      respondents, a life-threatening disease by 60%, a disease transmissible by
      consumption of pork meat by 10-21%, and a disease transmissible by contact with
      patients' saliva by 14.5% of patients and 44% of villagers (P<0.01). Stigma was
      high. People thought that they should avoid contact or sharing meals with
      patients (15% of patients, 62% of family members, P<0.001), and that persons with
      epilepsy should not get a job, get married (29 and 42%, P<0.016), or raise
      children (33-42%). CONCLUSION: Wrong beliefs may lead to stigma and hamper access
      to or compliance with modern epilepsy treatment. In traditional countries,
      education is the cornerstone of epilepsy management.

PMID- 17446141
TI  - Activity patterns of biotransformation enzymes in juvenile chickens after in ovo
      dosage of PCB126.
AB  - Little is known about the correlations between biotransformation enzymes in
      juvenile birds after exposure to environmental toxicants like PCBs. In this study
      eggs of domestic chicken (Gallus domesticus) were dosed with PCB126 in
      concentrations of 0.175-0.325 ng/g egg weight. Liver subcellular fractions were
      analyzed for activities of Phase 1 and Phase 2 biotransformation enzymes 2 and 5
      weeks post-hatch. Ethoxyresorufin O-deethylase (EROD) activity was increased in
      both the 2-week and 5-week samples. Glutathione-S-transferase (GST) activity was
      increased in the 2-week samples only, but the 5-week samples showed an overall
      much higher GST activity, probably as a result of a still developing enzyme
      expression in maturing chickens. The same pattern was seen in the phenol-type UDP
      glucuronosyltransferase (UGT) activity of the control animals. The week two
      samples showed a positive dose-response relationship for the UGT activity, but
      after 5 weeks this was reversed, possibly caused by inhibition of hydroxylated
      PCB metabolites. Phenol-type sulfotransferase (SULT) activities were not
      significantly correlated with time or dose. There was a strong positive
      regression between the Ah-receptor mediated EROD and UGT activities. The EROD
      activities were also positively correlated to the GST activities. Most
      interesting was a negative correlation between the UGT and SULT activities: an
      inhibited UGT activity appeared to be compensated by an increased SULT activity.

PMID- 17446142
TI  - Discovery of ubiquinone (coenzyme Q) and an overview of function.
AB  - Details of the discovery of ubiquinone (coenzyme Q) are described in the context
      of research on mitochondria in the early 1950s. The importance of the research
      environment created by David E. Green to the recognition of the compound and its
      role in mitochondria is emphasized as well as the dedicated work of Karl Folkers
      to find the medical and nutritional significance. The development of diverse
      functions of the quinone from electron carrier and proton carrier in mitochondria
      to proton transport in other membranes and uncoupling protein control as well as
      antioxidant and prooxidant functions is introduced. The successful application in
      medicine points the way for future development.

PMID- 17446143
TI  - The uptake and distribution of coenzyme Q10.
AB  - This review describes recent advances in our understanding of the uptake and
      distribution of coenzyme Q10 (CoQ10) in cells, animals, and humans. These
      advances have provided evidence of important pharmacokinetic factors, such as non
      linear absorption and enterohepatic recirculation, and may facilitate the
      development of new CoQ10 formulations. Studies providing data which support the
      claim of tissue uptake of exogenous CoQ10 are also discussed. Improved CoQ10
      dosing and drug level monitoring guidelines are suggested for adult and pediatric
      patient populations. Future CoQ10 research should consider uptake and
      distribution factors to determine cost-benefit relationships.

PMID- 17446144
TI  - Peripheral arterial chemoreceptors and sudden infant death syndrome.
AB  - Sudden infant death syndrome (SIDS) is the major cause of death in infants
      between 1 month and 1 year of age. Two particular concerns are that (1) premature
      or low birth weight (<2500-g) infants have a 2- to 40-fold greater risk of dying
      of SIDS (depending on the sleep position) than infants born at term and of normal
      birth weight, and that (2) the proportion of premature infants dying of SIDS has
      increased from 12 to 34% between 1988 and 2003. Hypo- and hypersensitivity of
      peripheral arterial chemoreceptors (PACs) may be one biological mechanism that
      could help to explain the epidemiological association between the increased
      incidence of SIDS in formerly premature infants. Because premature infants are
      often exposed to the extremes of oxygen stress during early postnatal
      development, they are more likely to have a maladaptive response of PACs later in
      their lives. As the first line of defense that mediates an increase in
      ventilation to a hypoxic challenge during wakefulness and sleep, PACs also
      mediate arousal responses during sleep in response to an asphyxial event that is
      often associated with upper airway obstruction. In most mammalian species, PACs
      are not fully developed at birth and thus are vulnerable to plasticity-induced
      changes mediated by environmental exposures such as the extremes of oxygen
      tension. Hypoxic or hyperoxic exposure during early postnatal development can
      lead to hyposensitive or hypersensitive PAC responses later in life. Although
      baseline chemoreceptor activity may not be the cause of an initial hypoxic or
      asphyxial event, the level of peripheral chemoreceptor drive does modulate the
      (1) time to arousal, (2) resumption of airflow during airway obstruction, (3)
      escape behaviors during rebreathing, and (4) cardiorespiratory responses that
      result from activation of the laryngeal chemoreflex. The laryngeal chemoreflex
      can be stimulated by reflux of gastric contents above the upper esophageal
      sphincter, or an increase in nasopharyngeal secretions from upper respiratory
      tract infections--events that contribute to some cases of SIDS. In this review,
      evidence is presented that both hypo- and hypersensitivity of PACs may be
      disadvantageous to the premature infant who is placed in an at risk environment
      for the occurrence of hypoxemia/asphyxia event thereby predisposing the infant to
      SIDS.

PMID- 17446145
TI  - Determination of Cloretazine (VNP40101M) and its active metabolite (VNP4090CE) in
      human plasma by liquid chromatography electrospray tandem mass spectrometry (LC
      ESI-MS/MS).
AB  - A sensitive method for the determination of Cloretazine (VNP40101M) and its
      metabolite (VNP4090CE) with an internal standard (ISTD) in human plasma was
      developed using high-performance liquid chromatographic separation with tandem
      mass spectrometric detection. Acidified plasma samples (500 microL) were prepared
      using solid phase extraction (SPE) columns, and 25 microL of the reconstituted
      sample was injected onto an Ascentis C18 HPLC column (3 microm, 5 cmx2.1 mm) with
      an isocratic mobile phase. Analytes were detected with an API-3000 LC-MS/MS
      System at unit (Q1) and low (Q3) resolution in negative multiple reaction
      monitoring mode: m/z 249.0 (precursor ion) to m/z 114.9 (product ion) for both
      Cloretazine (at 3.64 min) and VNP4090CE (at 2.91 min), and m/z 253.0 (precursor
      ion) to m/z 116.9 (product ion) for the ISTD. The mean recovery for Cloretazine
      (VNP40101M) and its metabolite (VNP4090CE) was greater than 87% with a lower
      limit of quantification of 1.0 ng/mL for Cloretazine (S/N=9.7, CV<or=12%) and 0.5
      ng/mL for VNP4090CE (S/N=11.3, CV<or=9.7%). This method was validated over a
      linear range of 1.0-1000 ng/mL for Cloretazine and 0.5-100 ng/mL for VNP4090CE,
      and results from a five day validation study demonstrated good within-day and
      between-day precision and accuracy. This method has been used to measure plasma
      Cloretazine and its metabolite concentrations in a Phase I study in children with
      recurrent progressive or refractory primary brain tumors.

PMID- 17446146
TI  - Investigation of the pharmacokinetics and determination of cholesteryl carbonate
      zidovudine in rat plasma by non-aqueous reversed-phase high performance liquid
      chromatography with UV detection.
AB  - A simple reversed phase high-performance liquid chromatographic method was
      established for the separation and quantification of a novel prodrug of
      zidovudine in rat plasma. Zidovudine was one of the original drugs used to treat
      HIV infection. Appropriate aliquots of rat plasma were spiked with cholesteryl
      carbonate zidovudine (AZTC) and treated with acetonitrile to precipitate plasma
      proteins. The supernatant after supercentrifugation was collected and an aliquot
      of 20 microL was injected directly into an HPLC system consisting of a Diamonsil
      C18 column and a diode array detector. The mobile phase consisted of methanol
      (85%, v/v) and diethyl ether (15%, v/v) at a flow rate of 1.0 mL/min. The
      extraction recoveries of AZTC at the three concentrations examined were all
      higher than 80%. The HPLC assay was linear over the concentration range 0.5-80
      microg/mL. A one-compartment model with apparent first-order elimination was used
      to describe the plasma concentration-time profile for AZTC after administration
      via the tail vein. The mean elimination half-life (t1/2) was 292.4 min. This RP
      HPLC method will be useful for the evaluation of the pharmacokinetics of AZTC in
      rats.

PMID- 17446147
TI  - Determination of ambroxol in human plasma by high performance liquid
      chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI).
AB  - A rapid, sensitive and specific method to determination of ambroxol in human
      plasma using high performance liquid chromatography coupled with electrospray
      ionization mass spectrometry (HPLC-MS/ESI) was described. Ambroxol and the
      internal standard (I.S.), fentanyl, were extracted from plasma by N-hexane
      diethyl ether (1:1, v/v) after alkalinized with ammonia water. A centrifuged
      upper layer was then evaporated and reconstituted with 100 microl mobile phase.
      Chromatographic separation was performed on a BDS HYPERSIL C18 column (250 mmx4.6
      mm, 5.0 microm, Thermo electron corporation, USA) with the mobile phase
      consisting of 30 mM ammonium acetate (0.4% formic acid)-acetonitrile (64:36, v/v)
      at a flow-rate of 1.2 mL min(-1). The total run time was 5.8 min for each sample.
      Detection and quantitation was performed by the mass spectrometer using selected
      ion monitoring at m/z 261.9, 263.8 and 265.9 for ambroxol and m/z 337.3 for
      fentanyl. The calibration curve was linear within the concentration range of 1.0
      100.0 ng mL(-1) (r=0.9996). The limit of quantification was 1.0 ng mL(-1). The
      extraction recovery was above 83.3%. The methodology recovery was higher than
      93.8%. The intra- and inter-day precisions were less than 6.0%. The method is
      accurate, sensitive and simple for the study of the pharmacokinetics and
      metabolism of ambroxol.

PMID- 17446148
TI  - Determinants of teenage pregnancies: the case of Busia District in Kenya.
AB  - Sub-Saharan Africa has one of the highest levels of teenage pregnancies in the
      world. In spite of that, there is paucity of empirical research on causes of
      teenage pregnancies in African countries. This paper investigates the
      determinants of teenage pregnancies based on a case study of Busia District in
      Kenya. The data are from a household survey conducted in 1998/1999. Empirical
      results indicate that girls' education level has significant influence on the
      probability of teenage birth, with non-schooling adolescents and those with
      primary school level education being more vulnerable. Among the variables used as
      proxies for access to sex education, availability of church forums that educate
      adolescents about sex and family life issues reduce probability of teenage
      pregnancy. Age is positively related to teenage pregnancies, with older
      adolescents being more predisposed to pregnancies. Though use of contraceptives
      is found to have a positive effect, only a small proportion of adolescents were
      using modern contraceptives and, supply side factors such as quality and
      availability were not accounted for. Other key factors as outlined by the
      adolescents themselves include peer pressure and social environment-related
      factors like inappropriate forms of recreation, which act as rendezvous for pre
      marital sex, as well as lack of parental guidance and counselling. Overall, lack
      of access to education opportunities, sex education and information regarding
      contraceptives, as well the widespread poverty predispose girls to teenage
      pregnancies. The problem of teenage pregnancies should be viewed within the
      broader socio-economic and socio-cultural environment in which the adolescents
      operate. For instance, lack of parental guidance on issues of sexuality and sex
      education was reinforced by cultural taboos that inhibit such discussions.
      Adolescents should be equipped with the relevant knowledge to enable them make
      informed choices regarding sexual relationships. This should be complemented with
      broader programmes aimed at promoting girl education and poverty alleviation.

PMID- 17446149
TI  - Emphysematous gastritis: case report and literature review.
AB  - Emphysematous gastritis is a rare variant of gastritis that is characterised by
      the presence of gas in the wall of the stomach with CT scan being the procedure
      of choice for diagnosis. It is a potentially fatal disease that is caused by gas
      forming organisms and usually presents with systemic toxicity. Predisposing
      factors include corrosive ingestion, alcohol abuse, abdominal surgery, diabetes,
      and immunosuppressant. Antimicrobial therapy with antibiotics covering gram
      negative organisms and anaerobes, and surgery in appropriate cases may enhance
      survival. We report a new case of emphysematous gastritis following pelvic
      surgery, diagnosed with a CT scan that showed gas in both stomach wall and liver
      portal venous distribution and recovered with conservative management.

PMID- 17446150
TI  - Epiperitoneal vessels: more resources to perform DIEP flaps.
AB  - The development of the DIEP flap established an accepted concept of
      reconstructive surgery, but in patients who demonstrate inadequate in vivo flap
      perfusion, alternative surgical options to improve vascularisation are limited.
      We present a 42-year-old patient, with a left mastectomy whose breast was
      reconstructed with a DIEP flap. After anastomosis to the internal mammary vessels
      there was insufficient arterial perfusion of the flap. The situation was resolved
      by using an independent medial perforator artery emerging from the peritoneal
      layer (epiperitoneal vessels). This new pedicle was anastomosed end-to-end to the
      distal portion of the inferior epigastric artery. We consider that epiperitoneal
      vessels can be an emergency pedicle when needed and a possible alternative to the
      main pedicle of the DIEP flap.

PMID- 17446151
TI  - A persisting median artery in a patient with symbrachydactyly and carpal tunnel
      syndrome.
AB  - A persisting median artery associated with carpal tunnel syndrome in a patient
      with symbrachydactyly has not been previously described in the literature. It is
      unclear whether there may be a developmental association between persistence of a
      median artery and Symbrachydactyly.

PMID- 17446152
TI  - The keystone design perforator island flap. Part I: anatomic study.
AB  - BACKGROUND: The keystone design perforator island flap has been described as a
      curvilinear shaped trapezoidal design flap that is essentially two V-Y flaps end
      to-side. Viability of the flap is thought to be supported by the subcutaneous
      vascular network and fascial and muscular perforators. The aim of this study was
      to assess the vascularisation of this flap and the behaviour of the skin paddle
      when submitted to important traction forces. METHODS: Fourteen flaps were raised
      after a skin defect was created on various regions of two fresh cadavers.
      Longitudinal and transversal cutaneous markings allowed analysis of the behaviour
      of the skin paddle during the course of direct closure and flap mobilisation.
      Injections of coloured solutions were performed before and after the flap
      elevation to visualise the vascularisation of the flap. DISCUSSION: The
      superficial vascular network was always preserved by the blunt dissection of the
      flap's margins and perforators arising from the underlying muscular tissue were
      constantly found. The dual vascularisation of the flap was then confirmed.
      Cutaneous markings showed the skin paddle to remain static in size with
      advancement of the surrounding tissues to meet the flap. The flap advancement
      opens a long and narrow defect on the lateral margin, the approximation of which
      in a V-Y fashion reduces even more the surface to be closed. Elevation of the
      flap also allows distribution of the tension forces over a greater surface both
      within the flap as well as the surrounding tissues. CONCLUSION: The vascular
      reliability of this flap and its versatile design potentially gives it a
      universal application all over the body.

PMID- 17446153
TI  - [Tropical medicine, a general medical practice in specific context].

PMID- 17446154
TI  - [A comparative study of the emergence of the AIDS and syphilis pandemics].
AB  - A historical and comparative study of the origins and emergence of syphilis and
      AIDS show that both result from human intrusions. Treponema probably existed in
      primates before human infection, and nonvenereal treponemal infection existed in
      prehistoric tropical Africa. When humans began wearing clothes, the disappearance
      of endemic infection ended immunity and led to receptivity to venereal infection.
      It was long thought that syphilis was first introduced in Europe by the
      conquistadors, but lesions typical of treponematosis dating from before the
      Common Era have been found in Europe. It is possible that the first navigators
      transferred treponemal infections to Latin America. AIDS seems to have appeared
      throughout the Congo River basin around 1950, and genetic studies attest to its
      long history in primates. It may have resulted from the Bantu migration and its
      strong human intrusion into the forest. After the initial human infection, new
      epidemiological factors in a transformed environment and behavioral changes led
      at 500-year intervals (1480-1490 for syphilis and 1940-1950 for AIDS) to the
      widespread emergence and subsequent pandemic of each disease.

PMID- 17446155
TI  - [Epidemiology of epilepsy in sub-Saharan Africa: a review].
AB  - Epilepsy is, above all tropical, moreover, very african in its frequency and
      gravity. Data on the prevalence of epilepsy shows it to be two or three times
      more prevalent in tropical zones than in industrialized countries in non tropical
      areas, however it is rare to find data on the incidence and prognosis of epilepsy
      in sub-Saharan Africa. It is difficult to determine the relative contribution of
      each of the causes of epilepsy. Only a few case-control studies have been carried
      out in sub-Saharan Africa. Infectious diseases, in particular parasitic diseases
      such as neurocysticercosis or cerebral malaria, seem to be the cause of the
      majority of the cases of epilepsy. However it is necessary to do additional
      epidemiological studies to determine the etiologies of epilepsy more precisely in
      sub-Saharan Africa.

PMID- 17446156
TI  - [Hepatitis E virus: an emerging disease].
AB  - Hepatitis E virus (HEV) is a spherical, non-enveloped, single stranded RNA virus.
      Four genotypes (1-4) have so far been distinguished. HEV infection can occur
      either in large epidemics (in endemic regions only: southeast Asia, India,
      central Asia central, Africa, and Mexico) or in sporadic forms. HEV is
      transmitted principally by the fecal-oral pathway, that is, hand-to-mouth. There
      is a risk of transmission from animals to humans. Nearly half of all cases have
      no or few symptoms. Symptomatic forms can be severe. The mortality rate can reach
      20% in pregnant women. Recent reports indicate that autochthonous cases have been
      contracted in France. Several aspects differentiate sporadic autochthonous
      hepatitis from that contracted in endemic areas: 1) mean age of onset is older in
      the former; 2) prognosis is more severe; and 3) prolonged even chronic forms can
      affect some immunocompromised patients, in particular, those with organ
      transplants. The diagnosis of hepatitis E must now be considered in any cases of
      acute hepatitis of unexplained origin in France. Diagnosis relies on RT-PCR
      testing of blood or stool.

PMID- 17446157
TI  - [Prevalence of helminths in a rural population using wastewater for agricultural
      purposes at Settat (Morocco)].
AB  - The aim of this investigation was to assess the risk associated with the use of
      unpurified wastewater for agricultural purposes, in particular, the risk of fecal
      transmission of intestinal helminths. The survey concerned 214 exposed subjects
      (mean age: 28.6 +/- 19.4 years; 52.8% female and 47.2% male) living in two
      villages that use raw wastewater for agriculture and 119 control subjects (mean
      age: 31.8 +/- 19.5 years, 50.4% female and 49.6% male), living in a village that
      does not use wastewater. All three villages are located around the city of
      Settat, in Morocco. All subjects agreeing to participate received a complete
      clinical examination, including a history, physical examination, and testing of
      stool samples taken on three consecutive days. The prevalence of intestinal
      helminths in the exposed population was 4.7%, compared with 0% for the control
      population, a statistically significant difference. Prevalence was slightly
      higher among men. Those at either end of the age spectrum were affected most
      heavily - essentially children aged from 3 to 14 years and those older than 60
      years. Ascaris lumbricoides is the helminth observed most frequently, with a
      prevalence of 4.2%. In conclusion, the use of raw wastewater in agriculture
      increases the risk of helminthiasis. Preventive measures are essential,
      especially health education and adequate treatment of used waters.

PMID- 17446158
TI  - [Malaria in mangrove areas of the Saloum delta (Senegal)].
AB  - This study of malaria biodiversity in Senegal used an entomological approach that
      combined parasite surveys and clinical investigations in the mangrove area of the
      Saloum delta from 1996 to 1998. The parasitologic studies took place in two of
      the six villages in the coastal area of Palmarin (Djifere and Diakhanor) during
      three distinct periods: at the end of the dry season, in the middle of the rainy
      season, and at the end of the rainy season. The clinical investigations at the
      Palmarin health station took place from July 1996 through February 1998. A
      malaria attack was defined as the presence of malaria symptoms (including fever,
      headaches, sweating, and shivering) associated with plasmodic parasitemia > 3,000
      trophozoites/microL of blood. All the positive thick smears were infected with
      Plasmodium falciparum, one also with P. falciparum, and none with P. ovale. The
      average plasmodic index (5.6%) classifies the delta of Saloum as a hypoendemic
      area. The average parasite load was estimated at 2,239 trophozoites (95% CI:
      1,660-3,020) of P. falciparum per microliter of blood, and 86.9% of patients with
      symptoms of a malaria attack were febrile. Malaria attacks accounted for 1.9% of
      the total consultations, 12.2% of the presumed malaria cases, and 14.0% of the
      febrile subjects. The finding that malaria attacks affected all age groups
      confirms the weakness of anti-malaria immunity among the population of the Saloum
      delta. Malaria cases were more frequent at the end of the rainy season and the
      beginning of the dry season, periods when parasite loads were highest. In this
      area, which is increasingly attractive to tourists and has a quite superficial
      fresh water table, man-made environmental changes favor mosquito breeding sites
      that promote the development of An. arabiensis and An. gambiae spp, both known to
      be major malaria vectors. In view of the population's weak anti-malaria immunity,
      this situation may increase malaria transmission and could be followed by
      epidemics. It is therefore important to set up a functional system of
      epidemiological monitoring to detect any malaria outbreaks.

PMID- 17446159
TI  - [Severe imported malaria: the experience of the Avicenna military hospital of
      Marrakech].
AB  - Incidence of severe imported malaria increases with the multiplication of
      humanitarian and military missions in malarial endemic areas. The purpose of this
      study was to describe the demographic, clinical, therapeutic and outcome aspects
      of 9 cases which have been hospitalized in the intensive care unit and medecine
      service of the military hospital of Marrakech, between january 2001 and december
      2004. Out of 68 patients admitted with symptomatic malaria during this period, 9
      cases were considered as severe. All of them were male soldiers (mean age: 33,3
      years), 7 of them have stayed in Democratic Republic of Congo, and 2 in Ivory
      Coast. Chemoprophylaxis consisted in chloroquine plus proguanil in 5 cases and
      mefloquine in 4 cases. The mean duration of stay in endemic area was 9,3 months.
      The clinical presentation was dominated by troubles of consciousness, which
      justified initial admission in the intensive care unit. The mean duration of
      hospitalization was 3,3 days in intensive care unit and 5,6 days in the medical
      department. Thick smear always revealed high parasitemia (5-15%) with Plasmodium
      falciparum, associated with Plasmodium ovale in two cases. Antimalarial treatment
      consisted in quinine salts administration. Evolution was favourable without
      recurrence in 7 cases, but 2 deaths were recorded. Severe imported malaria
      remains associated with bad outcome and requires early diagnosis and close
      monitoring of such cases.

PMID- 17446160
TI  - [Clinical trials of new therapeutic pharmacology for sickle cell disease].
AB  - Following the generation of transgenic mouse models of sickle cell disease, pre
      clinical trials have shown the beneficial effects of various potential
      therapeutic molecules for the acute or chronic manifestations of the disease.
      Several molecules are upon evaluation in phase I to phase III clinical trials.
      These therapeutic approaches target: 1) membrane cation transport systems and
      channels involved in sickle cell dehydration; 2) adherence of erythrocytes to
      endothelium; 3) activation of circulating and endothelial cells participating in
      the vasoocclusive events and local ischemia. The Gardos channel (calcium
      activated potassium channel KCNN4) is inhibited by the clotrimazole metabolite
      ICA17043, in phase III trial. The K-Cl co-transport (KCC1/3/4) activated by the
      depletion of erythrocyte magnesium is inhibited by Magnesium pidolate;
      dipyridamole inhibits ion transports upon deoxygenation. Sulfasalazyne (inhibitor
      of the NF-jB pathway) inhibits the abnormal activation of endothelial cells.
      Nitric oxide (NO) is the most potent vasodilator. It prevents the activation of
      leucocytes, platelets and endothelial cells in patients with sickle cell disease
      and vascular remodelling. The L-arginine, the NO precursor, provides could be
      beneficial in sickle cell patients.

PMID- 17446161
TI  - [Hemoglobinopathies and Plasmodium falciparum malaria: an example of negative
      epistatic effect].

PMID- 17446162
TI  - [Food crops in Sahelian countries: assessment and challenges].
AB  - Twenty-five years after the beggining of the policies of adjustment and
      liberalization which is the situation of the food crops in the countries of the
      Sahel? The balance-sheet is approached by contrasting the cereals sub sector,
      facing to a very strong control by the State, and the onion whose growth is
      related to the increase in the demand of the great urban centers. The increase in
      the production of cereals was accompanied by deep changes in the structures. The
      market became more efficient and better integrated on a regional scale. But, the
      level and the instability of the prices of cereals increased, making difficult
      the provisioning of the poor. Clear differences in trajectories appear. Mali,
      which implemented a policy of reforming cereals market and successful the revival
      of rice sector, must manage at the same time the improvement of the
      competitiveness of its cereals and the access to cereals of the low incomes
      consumers. Niger must face the increase in the vulnerability of a great part of
      the rural households. The production of onion experienced a spectacular increase
      in Senegal after the devaluation of franc FCA in response to the urban market.
      That of Niger intended mainly for the close countries progressed more slowly. But
      in both cases, the regulation of the European onion imports constitutes a
      paramount stake.

PMID- 17446164
TI  - The West Indies as a laboratory of biogeography and evolution.
AB  - Islands have long provided material and inspiration for the study of evolution
      and ecology. The West Indies are complex historically and geographically,
      providing a rich backdrop for the analysis of colonization, diversification and
      extinction of species. They are sufficiently isolated to sustain endemic forms
      and close enough to sources of colonists to develop a dynamic interaction with
      surrounding continental regions. The Greater Antilles comprise old fragments of
      continental crust, some very large; the Lesser Antilles are a more recent
      volcanic island arc, and the low-lying Bahama Islands are scattered on a shallow
      oceanic platform. Dating of island lineages using molecular methods indicates
      over-water dispersal of most inhabitants of the West Indies, although direct
      connections with what is now southern Mexico in the Early Tertiary, and
      subsequent land bridges or stepping stone islands linking to Central and South
      America might also have facilitated colonization. Species-area relationships
      within the West Indies suggest a strong role for endemic radiations and
      extinction in shaping patterns of diversity. Diversification is promoted by
      opportunities for allopatric divergence between islands, or within the large
      islands of the Greater Antilles, with a classic example provided by the Anolis
      lizards. The timing of colonization events using molecular clocks permits
      analysis of colonization-extinction dynamics by means of species accumulation
      curves. These indicate low rates of colonization and extinction for reptiles and
      amphibians in the Greater Antilles, with estimated average persistence times of
      lineages in the West Indies exceeding 30Myr. Even though individual island
      populations of birds might persist an average of 2Myr on larger islands in the
      Lesser Antilles, recolonization from within the archipelago appears to maintain
      avian lineages within the island chain indefinitely. Birds of the Lesser Antilles
      also provide evidence of a mass extinction event within the past million years,
      emphasizing the time-heterogeneity of historical processes. Geographical dynamics
      are matched by ecological changes in the distribution of species within islands
      over time resulting from adaptive radiation and shifts in habitat, often
      following repeatable patterns. Although extinction is relatively infrequent under
      natural conditions, changes in island environments as a result of human
      activities have exterminated many populations and others--especially old, endemic
      species--remain vulnerable. Conservation efforts are strengthened by recognition
      of aesthetic, cultural and scientific values of the unique flora and fauna of the
      West Indies.

PMID- 17446165
TI  - Regulation of cell proliferation by interleukin-3-induced nuclear translocation
      of pyruvate kinase.
AB  - Extracellular signaling molecules bound to cell surface receptors can regulate
      nuclear function with consequences for cell proliferation, differentiation, and
      function. To regulate nuclear function, signals must be transduced across the
      nuclear envelope to propagate the signal from the cytoplasm to the nucleus.
      Therefore, many signaling responses induce the nuclear translocation of
      transcription factors, kinases, and others. By using inducible translocation
      trap, a reporter gene-based system to detect inducible nuclear translocation, we
      found that the M2 isoform of pyruvate kinase, a key enzyme in glycolysis,
      translocates into the nucleus by interleukin-3, but not by epidermal growth
      factor, stimulation. The C domain of the M2 isoform of pyruvate kinase was
      sufficient for interleukin-3-induced nuclear translocation. Interleukin-3-induced
      nuclear translocation of the M2 isoform of pyruvate kinase was dependent on the
      activation of Jak2. Overexpression of the M2 isoform of pyruvate kinase protein
      fused with a nuclear localization signal enhanced cell proliferation in the
      absence of interleukin-3, suggesting that the nuclear pyruvate kinase plays an
      important role in cell proliferation.

PMID- 17446166
TI  - Common inhibitory serine sites phosphorylated by IRS-1 kinases, triggered by
      insulin and inducers of insulin resistance.
AB  - The Insulin Receptor Substrate (IRS) proteins are key players in insulin signal
      transduction and are the best studied targets of the insulin receptor. Ser/Thr
      phosphorylation of IRS proteins negatively modulates insulin signaling;
      therefore, the identification of IRS kinases and their target Ser phosphorylation
      sites is of physiological importance. Here we show that in Fao rat hepatoma
      cells, the IkappaB kinase beta (IKKbeta) is an IRS-1 kinase activated by selected
      inducers of insulin resistance, including sphingomyelinase, ceramide, and free
      fatty acids. Moreover, IKKbeta shares a repertoire of seven potential target
      sites on IRS-1 with protein kinase C zeta (PKCzeta), an IRS-1 kinase activated
      both by insulin and by inducers of insulin resistance. We further show that
      mutation of these seven sites (Ser-265, Ser-302, Ser-325, Ser-336, Ser-358, Ser
      407, and Ser-408) confers protection from the action of IKKbeta and PKCzeta when
      they are overexpressed in Fao cells or primary hepatocytes. This enables the
      mutated IRS proteins to better propagate insulin signaling. These findings
      suggest that insulin-stimulated IRS kinases such as PKCzeta overlap with IRS
      kinases triggered by inducers of insulin resistance, such as IKKbeta, to
      phosphorylate IRS-1 on common Ser sites.

PMID- 17446167
TI  - NAADP mobilizes calcium from the endoplasmic reticular Ca(2+) store in T
      lymphocytes.
AB  - The target calcium store of nicotinic acid adenine dinucleotide phosphate
      (NAADP), the most potent endogenous calcium-mobilizing compound known to date,
      has been proposed to reside in the lysosomal compartment or in the
      endo/sarcoplasmic reticulum. This study was performed to test the hypothesis of a
      lysosomal versus an endoplasmic reticular calcium store sensitive to NAADP in T
      lymphocytes. Pretreatment of intact Jurkat T cells with glycyl-phenylalanine 2
      naphthylamide largely reduced staining of lysosomes by LysoTracker Red and
      abolished NAADP-induced Ca(2+) signaling. However, the inhibitory effect was not
      specific since Ca(2+) mobilization by d-myo-inositol 1,4,5-trisphosphate and
      cyclic ADP-ribose was abolished, too. Bafilomycin A1, an inhibitor of the
      lysosomal H(+)-ATPase, did not block or reduce NAADP-induced Ca(2+) signaling,
      although it effectively prevented labeling of lysosomes by LysoTracker Red.
      Further, previous T cell receptor/CD3 stimulation in the presence of bafilomycin
      A1, assumed to block refilling of lysosomal Ca(2+) stores, did not antagonize
      subsequent NAADP-induced Ca(2+) signaling. In contrast to bafilomycin A1,
      emptying of the endoplasmic reticulum by thapsigargin almost completely prevented
      Ca(2+) signaling induced by NAADP. In conclusion, in T-lymphocytes, no evidence
      for involvement of lysosomes in NAADP-mediated Ca(2+) signaling was obtained. The
      sensitivity of NAADP-induced Ca(2+) signaling toward thapsigargin, combined with
      our recent results identifying ryanodine receptors as the target calcium channel
      of NAADP (Dammermann, W., and Guse, A. H. (2005) J. Biol. Chem. 280, 21394
      21399), rather suggest that the target calcium store of NAADP in T cells is the
      endoplasmic reticulum.

PMID- 17446168
TI  - Evidence for small ubiquitin-like modifier-dependent nuclear import of the
      thymidylate biosynthesis pathway.
AB  - Perturbations in folate-mediated one-carbon metabolism increase rates of uracil
      misincorporation into DNA during replication, impair cellular methylation
      reactions, and increase risk for neural tube defects and cancer. One-carbon
      metabolism is compromised by folate deficiency and common genetic polymorphisms.
      In this study, the mechanism for the preferential partitioning of cytoplasmic
      serine hydroxymethyltransferase (cSHMT)-derived methylenetetrahydrofolate to de
      novo thymidylate biosynthesis was investigated. The cSHMT enzyme was shown to
      interact with UBC9 and was a substrate for UBC9-catalyzed small ubiquitin-like
      modifier (SUMO) modification in vitro. SUMOylated cSHMT was detected in extracts
      from S phase MCF-7 cells, and cSHMT was shown to localize to the nucleus and
      nuclear periphery during the S and G(2)/M phases of the cell cycle. A common
      single nucleotide polymorphism (L474F-cSHMT) impaired the UBC9-cSHMT interaction
      and inhibited cSHMT SUMOylation in vitro. The three folate-dependent enzymes that
      constitute the de novo thymidylate biosynthesis pathway, cSHMT, thymidylate
      synthase, and dihydrofolate reductase, all contain SUMO modification consensus
      sequences. Compartmentation of the folate-dependent de novo thymidylate
      biosynthesis pathway in the nucleus accounts for the preferential partitioning of
      cSHMT-derived folate-activated one-carbon units into thymidylate biosynthesis;
      the efficiency of nuclear folate metabolism is likely to be modified by the cSHMT
      L474F polymorphism.

PMID- 17446169
TI  - Ataxia-telangiectasia mutated (ATM)-dependent activation of ATR occurs through
      phosphorylation of TopBP1 by ATM.
AB  - ATM (ataxia-telangiectasia mutated) is necessary for activation of Chk1 by ATR
      (ATM and Rad3-related) in response to double-stranded DNA breaks (DSBs) but not
      to DNA replication stress. TopBP1 has been identified as a direct activator of
      ATR. We show that ATM regulates Xenopus TopBP1 by phosphorylating Ser-1131 and
      thereby strongly enhancing association of TopBP1 with ATR. Xenopus egg extracts
      containing a mutant of TopBP1 that cannot be phosphorylated on Ser-1131 are
      defective in the ATR-dependent phosphorylation of Chk1 in response to DSBs but
      not to DNA replication stress. Thus, TopBP1 is critical for the ATM-dependent
      activation of ATR following production of DSBs in the genome.

PMID- 17446170
TI  - Insights into how CUB domains can exert specific functions while sharing a common
      fold: conserved and specific features of the CUB1 domain contribute to the
      molecular basis of procollagen C-proteinase enhancer-1 activity.
AB  - Procollagen C-proteinase enhancers (PCPE-1 and -2) are extracellular
      glycoproteins that can stimulate the C-terminal processing of fibrillar
      procollagens by tolloid proteinases such as bone morphogenetic protein-1. They
      consist of two CUB domains (CUB1 and -2) that alone account for PCPE-enhancing
      activity and one C-terminal NTR domain. CUB domains are found in several
      extracellular and plasma membrane-associated proteins, many of which are
      proteases. We have modeled the structure of the CUB1 domain of PCPE-1 based on
      known three-dimensional structures of CUB-containing proteins. Sequence alignment
      shows conserved amino acids, notably two acidic residues (Asp-68 and Asp-109)
      involved in a putative surface-located calcium binding site, as well as a
      conserved tyrosine residue (Tyr-67). In addition, three residues (Glu-26, Thr-89,
      and Phe-90) are found only in PCPE CUB1 domains, in putative surface-exposed
      loops. Among the conserved residues, it was found that mutations of Asp-68 and
      Asp-109 to alanine almost completely abolished PCPE-1 stimulating activity,
      whereas mutation of Tyr-67 led to a smaller reduction of activity. Among residues
      specific to PCPEs, mutation of Glu-26 and Thr-89 had little effect, whereas
      mutation of Phe-90 dramatically decreased the activity. Changes in activity were
      paralleled by changes in binding of different PCPE-1 mutants to a mini
      procollagen III substrate, as shown by surface plasmon resonance. We conclude
      that PCPE-stimulating activity requires a calcium binding motif in the CUB1
      domain that is highly conserved among CUB-containing proteins but also that PCPEs
      contain specific sites that could become targets for the development of novel
      anti-fibrotic therapies.

PMID- 17446171
TI  - Electron transport pathway for a Streptomyces cytochrome P450: cytochrome P450
      105D5-catalyzed fatty acid hydroxylation in Streptomyces coelicolor A3(2).
AB  - Streptomyces and other bacterial actinomycete species produce many important
      natural products, including the majority of known antibiotics, and cytochrome
      P450 (P450) enzymes catalyze important biosynthetic steps. Relatively few
      electron transport pathways to P450s have been characterized in bacteria,
      particularly streptomycete species. One of the 18 P450s in Streptomyces
      coelicolor A3(2), P450 105D5, was found to bind fatty acids tightly and form
      hydroxylated products when electrons were delivered from heterologous systems.
      The six ferredoxin (Fdx) and four flavoprotein Fdx reductase (FDR) proteins coded
      by genes in S. coelicolor were expressed in Escherichia coli, purified, and used
      to characterize the electron transfer pathway. Of the many possibilities, the
      primary pathway was NADH --> FDR1 --> Fdx4 --> P450 105D5. The genes coding for
      FDR1, Fdx4, and P450 105D5 are located close together in the S. coelicolor
      genome. Several fatty acids examined were substrates, including those found in S.
      coelicolor extracts, and all yielded several products. Mass spectra of the
      products of lauric acid imply the 8-, 9-, 10-, and 11-hydroxy derivatives.
      Hydroxylated fatty acids were also detected in vivo in S. coelicolor. Rates of
      electron transfer between the proteins were measured; all steps were faster than
      overall hydroxylation and consistent with rates of NADH oxidation. Substrate
      binding, product release, and oxygen binding were relatively fast in the
      catalytic cycle; high kinetic deuterium isotope effects for all four lauric acid
      hydroxylations indicated that the rate of C-H bond breaking is rate-limiting in
      every case. Thus, an electron transfer pathway to a functional Streptomyces P450
      has been established.

PMID- 17446172
TI  - Aging process modulates nonlinear dynamics in liver cell metabolism.
AB  - Regulatory dynamics of energy metabolism in living cells entails a coordinated
      response of multiple enzyme networks that operate under non-equilibrium
      conditions. Here we show that mitochondrial dysfunctions associated with the
      aging process significantly modify nonlinear dynamical signatures in free radical
      generation/removal, thereby altering energy metabolism in liver cells. We support
      our data with a plausible biochemical mechanism for modified bioenergetics that
      involves uncoupling protein-2 that is up-regulated in aged cells as an adaptive
      response to mitigate increased oxidative stress. Combining high spatial and
      temporal resolution imaging and bio-energetic measurements, our work provides
      experimental support to the hypothesis that mitochondria manifest nonlinear
      dynamical behavior for efficiently regulating energy metabolism in intact cells,
      and any partial or complete reduction in this behavior would contribute to organ
      dysfunctions including the aging process and other disease processes.

PMID- 17446173
TI  - Signaling by a non-dissociated complex of G protein betagamma and alpha subunits
      stimulated by a receptor-independent activator of G protein signaling, AGS8.
AB  - Accumulating evidence suggests that heterotrimeric G protein activation may not
      require G protein subunit dissociation. Results presented here provide evidence
      for a subunit dissociation-independent mechanism for G protein activation by a
      receptor-independent activator of G protein signaling, AGS8. AGS8 is a member of
      the AGS group III family of AGS proteins thought to activate G protein signaling
      primarily through interactions with Gbetagamma subunits. Results are presented
      demonstrating that AGS8 binds to the effector and alpha subunit binding "hot
      spot" on Gbetagamma yet does not interfere with Galpha subunit binding to
      Gbetagamma or phospholipase C beta2 activation. AGS8 stimulates activation of
      phospholipase C beta2 by heterotrimeric Galphabetagamma and forms a quaternary
      complex with Galpha(i1), Gbeta(1)gamma(2), and phospholipase C beta2. AGS8
      rescued phospholipase C beta binding and regulation by an inactive beta subunit
      with a mutation in the hot spot (beta(1)(W99A)gamma(2)) that normally prevents
      binding and activation of phospholipase C beta2. This demonstrates that, in the
      presence of AGS8, the hot spot is not used for Gbetagamma interactions with
      phospholipase C beta2. Mutation of an alternate binding site for phospholipase C
      beta2 in the amino-terminal coiled-coil region of Gbetagamma prevented AGS8
      dependent phospholipase C binding and activation. These data implicate a
      mechanism for AGS8, and potentially other Gbetagamma binding proteins, for
      directing Gbetagamma signaling through alternative effector activation sites on
      Gbetagamma in the absence of subunit dissociation.

PMID- 17446174
TI  - Necl-5/poliovirus receptor interacts in cis with integrin alphaVbeta3 and
      regulates its clustering and focal complex formation.
AB  - Integrin alphavbeta3, which forms focal complexes at leading edges in moving
      cells, is up-regulated in cancer cells and so is implicated in their
      invasiveness. Necl-5, originally identified as a poliovirus receptor and also up
      regulated in cancer cells, colocalizes with integrin alphavbeta3 at leading edges
      in moving cells and enhances growth factor-induced cell movement. Here, we show
      that Necl-5 interacts directly, in cis, with integrin alphavbeta3, and enhances
      integrin alphavbeta3 clustering and focal complex formation at leading edges in
      NIH3T3 cells. The extracellular region of Necl-5, but not the cytoplasmic region,
      is necessary for its interaction with integrin alphavbeta3; however, both regions
      are necessary for its action. An interaction between integrin alphavbeta3 and
      vitronectin and PDGF-induced activation of Rac are also necessary for integrin
      alphavbeta3 clustering. The interaction between Necl-5 and integrin alphavbeta3
      enhances PDGF-induced Rac activation, facilitating integrin alphavbeta3
      clustering presumably in a feedback amplification manner. Thus, Necl-5 has a
      critical role in integrin alphavbeta3 clustering and focal complex formation.

PMID- 17446176
TI  - Structural rearrangements between portal protein subunits are essential for viral
      DNA translocation.
AB  - Transport of DNA into preformed procapsids is a general strategy for genome
      packing inside virus particles. In most viruses, this task is accomplished by a
      complex of the viral packaging ATPase with the portal protein assembled at a
      specialized vertex of the procapsid. Such molecular motor translocates DNA
      through the central tunnel of the portal protein. A central question to
      understand this mechanism is whether the portal is a mere conduit for DNA or
      whether it participates actively on DNA translocation. The most constricted part
      of the bacteriophage SPP1 portal tunnel is formed by twelve loops, each
      contributed from one individual subunit. The position of each loop is stabilized
      by interactions with helix alpha-5, which extends into the portal putative ATPase
      docking interface. Here, we have engineered intersubunit disulfide bridges
      between alpha-5s of adjacent portal ring subunits. Such covalent constraint
      blocked DNA packaging, whereas reduction of the disulfide bridges restored normal
      packaging activity. DNA exit through the portal in SPP1 virions was unaffected.
      The data demonstrate that mobility between alpha-5 helices is essential for the
      mechanism of viral DNA translocation. We propose that the alpha-5 structural
      rearrangements serve to coordinate ATPase activity with the positions of portal
      tunnel loops relative to the DNA double helix.

PMID- 17446175
TI  - CD40 ligand-mediated activation of the de novo RelB NF-kappaB synthesis pathway
      in transformed B cells promotes rescue from apoptosis.
AB  - CD40, a tumor necrosis factor receptor family member, is expressed on B
      lymphocytes. Interaction between CD40 and its ligand (CD40L), expressed on
      activated T lymphocytes, is critical for B cell survival. Here, we demonstrate
      that CD40 signals B cell survival in part via transcriptional activation of the
      RelB NF-kappaB subunit. CD40L treatment of chronic lymphocytic leukemia cells
      induced levels of relB mRNA. Similarly, CD40L-mediated rescue of WEHI 231 B
      lymphoma cells from apoptosis induced upon B cell receptor (surface IgM)
      engagement led to increased relB mRNA levels. Recently, we characterized a new de
      novo synthesis pathway for the RelB NF-kappaB subunit, induced by the
      cytomegalovirus IE1 protein, in which binding of p50/p65 NF-kappaB and c-Jun/Fra
      2 AP-1 complexes to the relB promoter works in synergy to potently activate
      transcription (Wang, X., and Sonenshein, G. E. (2005) J. Virol. 79, 95-105).
      CD40L treatment of WEHI 231 cells caused induction of AP-1 family members Fra-2,
      c-Jun, JunD, and JunB. Cotransfection of Fra-2 with the Jun AP-1 subunits and
      p50/c-Rel NF-kappaB led to synergistic activation of the relB promoter. Ectopic
      expression of relB or RelB knockdown using small interfering RNA demonstrated the
      important role of this subunit in control of WEHI 231 cell survival and
      implicated activation of the anti-apoptotic factors Survivin and manganese
      superoxide dismutase. Thus, CD40 engagement of transformed B cells activates relB
      gene transcription via a process we have termed the de novo RelB synthesis
      pathway, which protects these cells from apoptosis.

PMID- 17446177
TI  - Lumazine synthase from Candida albicans as an anti-fungal target enzyme:
      structural and biochemical basis for drug design.
AB  - Lumazine synthase is an enzyme involved in riboflavin biosynthesis in many plants
      and microorganisms, including numerous human pathogens. The fact that the enzymes
      of the riboflavin biosynthesis pathway are not present in the human or animal
      host makes them potential targets for anti-infective agents. The crystal
      structure of lumazine synthase from Candida albicans was solved by molecular
      replacement and refined at 2.5-Angstrom resolution. The results of
      crystallographic investigations and sedimentation equilibrium experiments clearly
      indicated the presence of pentameric assemblies of the enzyme either in crystals
      or in solution. Isothermal titration calorimetry measurements of the binding
      reactions of four different inhibitors revealed high affinity for all four
      compounds with binding constants in the micromolar range. Structural comparison
      with previously determined structures of the enzyme.ligand complexes of other
      orthologue allowed modeling of the binding of four different inhibitors into the
      active site of lumazine synthase from Candida albicans.

PMID- 17446178
TI  - The endogenous estradiol metabolite 2-methoxyestradiol reduces atherosclerotic
      lesion formation in female apolipoprotein E-deficient mice.
AB  - Estradiol, the major endogenous estrogen, reduces experimental atherosclerosis
      and metabolizes to 2-methoxyestradiol in vascular cells. Currently undergoing
      evaluation in clinical cancer trials, 2-methoxyestradiol potently inhibits cell
      proliferation independently of the classical estrogen receptors. This study
      examined whether 2-methoxyestradiol affects atherosclerosis development in female
      mice. Apolipoprotein E-deficient mice, a well-established mouse model of
      atherosclerosis, were ovariectomized and treated through slow-release pellets
      with placebo, 17beta-estradiol (6 microg/d), or 2-methoxyestradiol [6.66 microg/d
      (low-dose) or 66.6 microg/d (high-dose)]. After 90 d, body weight gain decreased
      and uterine weight increased in the high-dose but not low-dose 2-methoxyestradiol
      group. En face analysis showed that the fractional area of the aorta covered by
      atherosclerotic lesions decreased in the high-dose 2-methoxyestradiol (52%) but
      not in the low-dose 2-methoxyestradiol group. Total serum cholesterol levels
      decreased in the high- and low-dose 2-methoxyestradiol groups (19%, P < 0.05 and
      21%, P = 0.062, respectively). Estradiol treatment reduced the fractional
      atherosclerotic lesion area (85%) and decreased cholesterol levels (42%). In
      conclusion, our study shows for the first time that 2-methoxyestradiol reduces
      atherosclerotic lesion formation in vivo. The antiatherogenic activity of an
      estradiol metabolite lacking estrogen receptor activating capacity may argue that
      trials on cardiovascular effects of hormone replacement therapy should use
      estradiol rather than other estrogens. Future research should define the role of
      2-methoxyestradiol as a mediator of the antiatherosclerotic actions of estradiol.
      Furthermore, evaluation of the effects of 2-methoxyestradiol on cardiovascular
      disease endpoints in ongoing clinical trials is of great interest.

PMID- 17446179
TI  - Steroid-producing cells regulate arterial tone of adrenal cortical arteries.
AB  - Adrenal blood flow is coupled to adrenal hormone secretion. ACTH increases
      adrenal blood flow and stimulates the secretion of aldosterone and cortisol in
      vivo. However, ACTH does not alter vascular tone of isolated adrenal cortical
      arteries. Mechanisms underlying this discrepancy remain unsolved. The present
      study examined the effect of zona glomerulosa (ZG) cells on cortical arterial
      tone. ZG cells (10(5) to 10(7) cells) and ZG cell-conditioned medium relaxed
      preconstricted adrenal arteries (maximal relaxations = 79 +/- 4 and 66 +/- 4%,
      respectively). In adrenal arteries coincubated with a small number of ZG cells
      (0.5-1 x 10(6)), ACTH (10(-12) to 10(-8) m) induced concentration-dependent
      relaxations (maximal relaxation = 67 +/- 4%). Similarly, ACTH (10(-8) m) dilated
      (55 +/- 10%) perfused arteries embedded in adrenal cortical slices. ZG cell
      dependent relaxations to ACTH were endothelium-independent and inhibited by high
      extracellular K(+) (60 mm); the K(+) channel blocker, iberiotoxin (100 nm); the
      cytochrome P450 inhibitors SKF 525A (10 microm) and miconazole (10 microm); and
      the epoxyeicosatrienoic acid (EET) antagonist 14,15-EEZE (2 microm). Four EET
      regioisomers were identified in ZG cell-conditioned media. EET production was
      stimulated by ACTH. We conclude that ZG cells release EETs and this release is
      stimulated by ACTH. Interaction of endocrine and vascular cells represents a
      mechanism for regulating adrenal blood flow and couples steroidogenesis to
      increased blood flow.

PMID- 17446180
TI  - The role of repressor proteins in the adrenergic induction of type II
      iodothyronine deiodinase in rat pinealocytes.
AB  - In this study, we investigated the transcriptional regulation of the adrenergic
      induction of type II iodothyronine deiodinase (Dio2) in rat pinealocytes.
      Treatment of pinealocytes with norepinephrine (NE) caused an increase in the mRNA
      level of Dio2 that peaked around 2 h and declined over the next 5 h. Both beta-
      and alpha1-adrenergic receptors contributed to the NE induction of Dio2
      expression through a cAMP/protein kinase A mechanism. In pinealocytes that had
      been stimulated by NE, inhibition of transcription by actinomycin had no
      discernible effect on Dio2 expression. In contrast, inhibition of protein
      synthesis by cycloheximide enhanced the NE induction of Dio2 expression,
      suggesting the involvement of a repressor protein. Transient transfection of
      pinealocytes with adenovirus expressing small interfering RNA against Fos-related
      antigen 2 (Fra2) enhanced the NE induction of Dio2 expression, whereas the effect
      of overexpression of the full-length transcript of Fra2 was inhibitory. Time
      course study indicated that preventing the NE induction of Fra2 enhanced the NE
      induction of Dio2 after 3 h, and the enhancement persisted beyond 6 h after NE
      stimulation. In comparison, transient transfection of pinealocytes with small
      interfering RNA against inducible cAMP early repressor (Icer) had no effect on
      the NE induction of Dio2 expression, whereas overexpression of the full-length
      transcript of Icer caused a small reduction of the NE-stimulated Dio2 expression.
      Together, our results support Fra-2 as an important transcriptional repressor
      that helps shape the time profile of the adrenergic induction of Dio2 expression
      in the rat pineal gland.

PMID- 17446181
TI  - Presence of sex steroids and cytochrome P450 genes in amphioxus.
AB  - The presence of sex steroids and their receptors has been demonstrated in all
      vertebrate groups from Agnatha to Mammalia but not in invertebrates. In genomic
      analyses of urochordates, cytochrome P450 (CYP) genes important for biosynthesis
      of sex steroids are absent. In the present study, we confirmed the presence of
      estrogen, androgen, and progesterone by using radioimmunoassay in gonads of
      amphioxus, Branchiostoma belcheri, which is considered to be evolutionarily
      closer to vertebrates than other invertebrates. Furthermore, CYP genes encoding
      CYP11A, CYP17, and CYP19 and transcripts for 17beta-hydroxysteroid dehydrogenase
      were cloned from amphioxus ovaries. Among invertebrates, the presence of
      hydroxysteroid dehydrogenase enzymes and metabolized steroids was shown in
      paracytic Taenia and corals. However, CYPs metabolizing sex steroids have not
      been demonstrated in invertebrates, nor has an attempt been made to consider the
      entire pathway from cholesterol to estrogen. This study is the first evidence to
      suggest the presence of CYP enzymes in sex steroid production in invertebrates.

PMID- 17446182
TI  - Estradiol, progesterone, and genistein inhibit oocyte nest breakdown and
      primordial follicle assembly in the neonatal mouse ovary in vitro and in vivo.
AB  - In developing mouse ovaries, oocytes develop as clusters of cells called nests or
      germ cell cysts. Shortly after birth, oocyte nests dissociate and granulosa cells
      surround individual oocytes forming primordial follicles. At the same time, two
      thirds of the oocytes die by apoptosis, but the link between oocyte nest
      breakdown and oocyte death is unclear. Although mechanisms controlling breakdown
      of nests into individual oocytes and selection of oocytes for survival are
      currently unknown, steroid hormones may play a role. Treatment of neonatal mice
      with natural or synthetic estrogens results in abnormal multiple oocyte follicles
      in adult ovaries. Neonatal genistein treatment inhibits nest breakdown suggesting
      multiple oocyte follicles are nests that did not break down. Here we investigated
      the role of estrogen signaling in nest breakdown and oocyte survival. We
      characterized an ovary organ culture system that recapitulates nest breakdown,
      reduction in oocyte number, primordial follicle assembly, and follicle growth in
      vitro. We found that estradiol, progesterone, and genistein inhibit nest
      breakdown and primordial follicle assembly but have no effect on oocyte number
      both in organ culture and in vivo. Fetal ovaries, removed from their normal
      environment of high levels of pregnancy hormones, underwent premature nest
      breakdown and oocyte loss that was rescued by addition of estradiol or
      progesterone. Our results implicate hormone signaling in ovarian differentiation
      with decreased estrogen and progesterone at birth as the primary signal to
      initiate oocyte nest breakdown and follicle assembly. These findings also provide
      insight into the mechanism of multiple oocyte follicle formation.

PMID- 17446183
TI  - Chronic gonadotropin-releasing hormone inhibits activin induction of the ovine
      follicle-stimulating hormone beta-subunit: involvement of 3',5'-cyclic adenosine
      monophosphate response element binding protein and nitric oxide synthase type I.
AB  - FSH is induced by activin, and this expression is modulated by GnRH through FSHB
      expression. This report focuses on the inhibitory effect of GnRH on activin
      induced FSHB expression. Activin-treated primary murine pituitary cultures
      robustly express mutant ovine FSHBLuc-DeltaAP1, a luciferase transgene driven by
      4.7 kb of ovine FSHB promoter. This promoter lacks two GnRH-inducible activator
      protein-1 sites, making it easier to observe GnRH-mediated inhibition. Luciferase
      expression from this transgene was decreased 94% by 100 nM GnRH with a half-time
      of approximately 4 h in pituitary cultures, and this inhibition was independent
      of follistatin. Activators of cAMP and protein kinase C like forskolin and
      phorbol 12-myristate 3-acetate (PMA), respectively, mimicked GnRH action. Kinetic
      studies of wild-type ovine FSHBLuc in LbetaT2 cells showed continuous induction
      by activin (4-fold) over 20 h. Most of this induction (78%) was blocked,
      beginning at 6 h. cAMP response element binding protein (CREB) was implicated in
      this inhibition because overexpression of its constitutively active mutant
      mimicked GnRH, and its inhibitor (inducible cAMP early repressor isoform II)
      reversed the inhibition caused by GnRH, forskolin, or PMA. In addition, GnRH,
      forskolin, or PMA increased the expression of a CREB-responsive reporter gene,
      6xCRE-37PRL-Luc. Inhibition of nitric oxide type I (NOSI) by 7-nitroindazole also
      reversed GnRH-mediated inhibition by 60%. It is known that GnRH and CREB induce
      production of NOSI in gonadotropes and neuronal cells, respectively. These data
      support the concept that chronic GnRH inhibits activin-induced ovine FSHB
      expression by sequential activation of CREB and NOSI through the cAMP and/or
      protein kinase C pathways.

PMID- 17446184
TI  - Interactions of diethylstilbestrol (DES) and DES analogs with membrane progestin
      receptor-alpha and the correlation with their nongenomic progestin activities.
AB  - Progestin induction of oocyte maturation (OM) in fish is a useful model for
      investigating endocrine disruption of nongenomic steroid actions. Although
      diethylstilbestrol (DES) analogs have been shown to mimic the actions of
      progestins to induce meiotic maturation of goldfish and zebrafish oocytes, their
      molecular mechanisms of action remain unclear. The ability of these endocrine
      disrupting chemicals (EDCs) to interact with the progestin receptor mediating OM
      was investigated in receptor binding assays using plasma membranes from goldfish
      ovaries and breast cancer cells transfected with goldfish membrane progestin
      receptor (mPR)-alpha. Membranes prepared from both ovaries and mPRalpha
      transfected cells showed high-affinity, saturable, displaceable, single binding
      sites specific for the goldfish maturation-inducing steroid, 17alpha,20beta
      dihydroxy-4-pregnen-3-one (17,20beta-DHP). DES and DES analogs (dipropionate-DES
      and hexestrol), which induce OM in goldfish, bound to the receptor and caused
      concentration-dependent displacement of [3H]-17,20beta-DHP, whereas dimethyl
      ether-DES had no affinity for the receptor. Scatchard plot analysis of specific
      17,20beta-DHP binding in the presence of different amounts of DES showed that DES
      binding is of the noncompetitive type. The activities of DES and DES analogs to
      induce meiotic maturation of goldfish oocytes were examined in an in vitro
      bioassay. Whereas a concentration-dependent induction of OM was observed in
      response to DES, dipropionate-DES, and hexestrol, dimethyl ether-DES did not show
      any OM-inducing activity. The close correspondence between binding of DES and its
      analogs to the mPRalpha protein and their OM-inducing activities suggests a
      mechanism of endocrine disruption mediated by binding to mPRalpha resulting in
      its activation, thereby mimicking the nongenomic action of the progestin
      17,20beta-DHP.

PMID- 17446185
TI  - An increase in murine skeletal muscle peroxisome proliferator-activated receptor
      gamma coactivator-1alpha (PGC-1alpha) mRNA in response to exercise is mediated by
      beta-adrenergic receptor activation.
AB  - A single bout of exercise increases expression of peroxisome proliferator
      activated receptor-gamma coactivator (PGC)-1alpha mRNA, which may promote
      mitochondrial biogenesis in skeletal muscle. In brown adipose tissue, cold
      exposure up-regulates PGC-1alpha expression via adrenergic receptor (AR)
      activation. Because exercise also activates the sympathetic nervous system, we
      examined whether exercise-induced increase in PGC-1alpha mRNA expression in
      skeletal muscle was mediated via AR activation. In C57BL/6J mice, injection of
      the beta2-AR agonist clenbuterol, but not alpha-, beta1-, or beta3-AR agonists,
      increased PGC-1alpha mRNA expression more than 30-fold in skeletal muscle. The
      clenbuterol-induced increase in PGC-1alpha mRNA expression in mice was inhibited
      by pretreatment with the beta-AR antagonist propranolol. In ex vivo experiments,
      direct exposure of rat epitrochlearis to beta2-AR agonist, but not alpha-, beta1
      , and beta3-AR agonist, led to an increase in levels of PGC-1alpha mRNA.
      Injection of beta2-AR agonist did not increase PGC-1alpha mRNA expression in
      beta1-, beta2-, and beta3-AR knockout mice (beta-less mice). PGC-1alpha mRNA in
      gastrocnemius was increased 3.5-fold in response to running on a treadmill for 45
      min. The exercise-induced increase in PGC-1alpha mRNA was inhibited by
      approximately 70% by propranolol or the beta2-AR-specific inhibitor ICI 118,551.
      The exercise-induced increase in PGC-1alpha mRNA in beta-less mice was also 36%
      lower than that in wild-type mice. These data indicate that up-regulation of PGC
      1alpha expression in skeletal muscle by exercise is mediated, at least in part,
      by beta-ARs activation. Among ARs, beta2-AR may mediate an increase in PGC-1alpha
      by exercise.

PMID- 17446186
TI  - Tumor necrosis factor-alpha induces insulin resistance in endothelial cells via a
      p38 mitogen-activated protein kinase-dependent pathway.
AB  - Chronic inflammation contributes to vascular insulin resistance and endothelial
      dysfunction. Systemic infusion of TNF-alpha abrogates insulin's action to enhance
      skeletal muscle microvascular perfusion. In skeletal muscle TNF-alpha induces
      insulin resistance via the p38 MAPK pathway. To examine whether p38 MAPK also
      regulates TNF-alpha-induced vascular insulin resistance, bovine aortic
      endothelial cells (bAECs) were incubated+/-TNF-alpha (5 ng/ml) for 6 h in the
      presence or absence of SB203580 (p38 MAPK specific inhibitor, 10 microM) after
      serum starvation for 10 h. For the last 30 min, cells were treated+/-1 nM
      insulin, and insulin receptor substrate (IRS)-1, Akt, endothelial nitric oxide
      synthase (eNOS), p38 MAPK, ERK1/2, c-Jun N-terminal kinase, and AMP-activated
      protein kinase (AMPK) phosphorylation, and eNOS activity were measured. TNF-alpha
      increased p38 MAPK phosphorylation, potently stimulated IRS-1 serine
      phosphorylation, and blunted insulin-stimulated IRS-1 tyrosine and Akt
      phosphorylation and eNOS activity. TNF-alpha also potently stimulated the
      phosphorylation of ERK1/2 and AMPK. Treatment with SB203580 decreased p38 MAPK
      phosphorylation back to the baseline and restored insulin sensitivity of IRS-1
      tyrosine and Akt phosphorylation and eNOS activity in TNF-alpha-treated bAECs
      without affecting TNF-alpha-induced ERK1/2 and AMPK phosphorylation. We conclude
      that in cultured bAECs, TNF-alpha induces insulin resistance in the
      phosphatidylinositol 3-kinase/Akt/eNOS pathway via a p38 MAPK-dependent mechanism
      and enhances ERK1/2 and AMPK phosphorylation independent of the p38 MAPK pathway.
      This differential modulation of TNF-alpha's actions by p38 MAPK suggests that p38
      MAPK plays a key role in TNF-alpha-mediated vascular insulin resistance and may
      contribute to the generalized endothelial dysfunction seen in type 2 diabetes
      mellitus and the cardiometabolic syndrome.

PMID- 17446187
TI  - Activation of the thyroid-stimulating hormone beta-subunit gene by LIM
      homeodomain transcription factor Lhx2.
AB  - Although there is evidence that the LIM homeodomain transcription factor, Lhx2,
      can stimulate transcription of the glycoprotein hormone alpha-subunit gene, the
      role of Lhx2 in regulating TSH beta-subunit has not been established. In the
      present studies, the ability of Lhx2 to regulate transcription of the TSH beta
      subunit gene was examined. In the thyrotrope-derived TalphaT1 cell line, Lhx2
      expression was found to be induced by treatment with either TRH or cAMP,
      consistent with the possibility that Lhx2 may play a role in mediating the
      ability of this signaling pathway to stimulate TSH gene expression. Transient,
      forced overexpression of Lhx2 stimulated activity of a TSH beta-subunit reporter
      gene. Deletion studies provided evidence that the -177 to -79 region of the TSH
      beta-subunit promoter was necessary for stimulation of reporter gene activity by
      Lhx2. A gel mobility shift assay provided the evidence that Lhx2 can bind to this
      region of DNA. DNase I footprinting studies demonstrated that two distinct
      regions of the TSHbeta promoter, -118 to -108 and -86 to -68, are protected by
      Lhx2 from nuclease digestion. These regions contain repeats of the sequence, 5'
      (G/T)CAAT(T/A)-3'. Mutation of this sequence, especially in the -86 to -68
      region, substantially decreased Lhx2 responsiveness of the TSH beta-subunit
      reporter gene. In addition, a DNA fragment containing the -177 to -79 region of
      the TSHbeta promoter was found to confer Lhx2 responsiveness to a minimal
      promoter. These results provide multiple lines of evidence consistent with a role
      for Lhx2 in modulating expression of the TSH beta-subunit gene.

PMID- 17446188
TI  - Developmental programming: follicular persistence in prenatal testosterone
      treated sheep is not programmed by androgenic actions of testosterone.
AB  - Testosterone (T) treatment during early-midgestation (30-90 d; term is 147 d)
      leads to reproductive cycle defects. Daily ultrasonography in prenatal T-treated
      female sheep during the first two breeding seasons revealed an increase in the
      number of large follicles and follicular persistence. The objective of this study
      was to determine whether follicular persistence in prenatal T-treated females was
      programmed by the androgenic actions of T. Pregnant Suffolk ewes were injected
      with 100 mg (im; twice weekly) of T propionate or dihydrotestosterone (DHT, a
      nonaromatizable androgen) in cottonseed oil from d 30 to d 90 of gestation. Prior
      to daily transrectal ovarian ultrasonography, estrus was synchronized with two
      injections of 20 mg of prostaglandin F2alpha (PGF2alpha) given 11 d apart in two
      consecutive years. In yr 1 ultrasonography began 14 d after PGF2alpha, during the
      presumptive luteal phase, and continued until subsequent ovulation and corpora
      lutea were detected (10-13 d). In yr 2, ultrasonography began 2 d before the last
      PGF2alpha injection and concluded 25 d after the last PGF2alpha injection. Daily
      changes in appearance and disappearance of ovarian follicles and follicular sizes
      were assessed. Prenatal DHT, but not prenatal T, treatment increased the total
      number of follicles by increasing the number of small follicles. Prenatal T, but
      not DHT, treatment increased (P<0.05) the number of large follicles with the
      majority of prenatal T-treated females manifesting follicular persistence. The
      data indicate that occurrence of large-sized follicles and follicular persistence
      in prenatal T-treated females are not programmed by androgenic actions but likely
      are programmed by estrogenic actions stemming from aromatization of T to
      estradiol.

PMID- 17446189
TI  - Dlk1/FA1 is a novel endocrine regulator of bone and fat mass and its serum level
      is modulated by growth hormone.
AB  - Fat and bone metabolism are two linked processes regulated by several hormonal
      factors. Fetal antigen 1 (FA1) is the soluble form of dlk1 (delta-like 1), which
      is a member of the Notch-Delta family. We previously identified FA1 as a negative
      regulator of bone marrow mesenchymal stem cell differentiation. Here, we studied
      the effects of circulating FA1 on fat and bone mass in vivo by generating mice
      expressing high serum levels of FA1 (FA1 mice) using the hydrodynamic-based gene
      transfer procedure. We found that increased serum FA1 levels led to a significant
      reduction in total body weight, fat mass, and bone mass in a dose-dependent
      manner. Reduced bone mass in FA1 mice was associated with the inhibition of
      mineral apposition rate and bone formation rates by 58 and 72%, respectively.
      Because FA1 is colocalized with GH in the pituitary gland, we explored the
      possible modulation of serum FA1 by GH. Serum levels of IGF-I and IGF binding
      proteins did not change in FA1 mice, whereas increasing serum GH in normal mice
      using hydrodynamic-based gene transfer procedure dramatically reduced serum FA1
      levels by 60%. Conversely, serum FA1 was increased 450% in hypophysectomized
      mice, and this high level was reduced by 40% during GH treatment. In conclusion,
      our data identify the FA1 as a novel endocrine factor regulating bone mass and
      fat mass in vivo, and its serum levels are regulated by GH. FA1 thus provides a
      novel class of developmental molecules that regulate physiological functions of
      the postnatal organisms.

PMID- 17446190
TI  - Upstream stimulatory factor regulates constitutive expression and hormonal
      suppression of the 90K (Mac-2BP) protein.
AB  - We previously reported that hormones important for the normal growth and function
      of FRTL-5 rat thyroid cells, TSH, or its cAMP signal plus insulin or IGF-I, could
      transcriptionally suppress constitutive and gamma-interferon (IFN)-increased
      synthesis of the 90K protein (also known as Mac-2BP). Here we cloned the 5'
      flanking region of the rat 90K gene and identified a minimal promoter containing
      an interferon response element and a consensus E-box or upstream stimulator
      factor (USF) binding site, which are highly conserved in both the human and
      murine genes. We show that suppression of constitutive and gamma-IFN-increased
      90K gene expression by TSH/cAMP plus insulin/IGF-I depends on the ability of the
      hormones to decrease the binding of USF to the E-box, located upstream of the
      interferon response element. This site is required for the constitutive
      expression of the 90K gene. Transfection with USF1 and USF2 cDNAs increases
      constitutive promoter activity, attenuates the ability of TSH/cAMP plus
      insulin/IGF-I to decrease constitutive or gamma-IFN-increased 90K gene expression
      but does not abrogate the ability of gamma-IFN itself to increase 90K gene
      expression.

PMID- 17446191
TI  - Platelets are novel regulators of neovascularization and luteinization during
      human corpus luteum formation.
AB  - The human corpus luteum is a unique endocrine organ that is periodically
      constructed from the ovulated follicle. During human corpus luteum formation,
      which is well known as a pathophysiological model for tissue remodeling, the
      precise mechanisms by which centripetal vascular development is regulated remain
      unknown. Recently platelets were reported to contain chemoattractive substances
      with the potential to induce endothelial migration. In this study, we examined
      the involvement of platelets in the early tissue remodeling process of the human
      corpus luteum. An immunohistochemical study demonstrated that considerable
      amounts of red blood cells and CD41-positive platelets were localized at
      extravascular sites among luteinizing granulosa cells after ovulation. Platelet
      deposition gradually decreased and became limited near the central cavity toward
      which microvessels were extending. Platelets were hardly observed in the
      midluteal phase when the vascular network had already been established. These
      platelets expressed CD62P/P-selectin and were colocalized with extracellular
      matrix, suggesting that platelets had been activated by the extracellular matrix.
      Progesterone production by luteinizing granulosa cells that were isolated from
      patients undergoing in vitro fertilization therapy was significantly promoted by
      direct contact with platelets during 4-d culture. Platelet-derived soluble
      factors induced spreading in granulosa cell morphology. These factors also
      increased the migration of human umbilical vein endothelial cells, whereas
      luteinizing granulosa cells attenuated platelet-induced endothelial cell
      migration. These findings lead us to propose the novel concept that platelets are
      regulators of endothelial cell migration and granulosa cell luteinization in the
      remodeling process of the human corpus luteum.

PMID- 17446192
TI  - Redefining ancestral relationships in pituitary cell genealogy.

PMID- 17446194
TI  - A longitudinal study of emergency medicine residents' malpractice fear and
      defensive medicine.
AB  - OBJECTIVES: To determine the baseline level and evolution of defensive medicine
      and malpractice concern (MC) of emergency medicine (EM) residents. METHODS: Using
      a validated instrument consisting of case scenarios and Likert-type scale
      questions, the authors performed a prospective, longitudinal (June 2001 to June
      2005) study of EM residents at five 4-year California residency programs.
      RESULTS: All 51 EM interns of these residencies were evaluated; four residents
      left their programs and one took medical leave, resulting in 46 graduating
      residents evaluated. MC did not affect the residency choice of interns. Although
      perceived likelihood of serious disease increased in case scenarios over time,
      defensive medicine decreased in 27% of cases and increased in 20%. On a scale
      with 1 representing extremely influential and 5 representing not at all
      influential, the mean (+/-SD) influence of MC on interns' and graduates' case
      evaluation and management was 2.5 (+/-1.1) and 2.7 (+/-1.0), respectively.
      Comparing interns and graduates, there was no significant difference in the
      percentages of respondents who declared MC (mean difference in proportions, 3.3%;
      95% CI = -8.4% to 15%) or refused procedures because of MC (11.5%; 95% CI = -1.3%
      to 24.3%). More interns, however, declared substantial loss of enjoyment of
      medicine than graduates (48%; 95% CI = 30.3% to 65.5%). CONCLUSIONS: Physicians
      enter four-year EM residencies in California with moderate MC and defensive
      medicine, which do not change significantly over time and do not markedly impact
      their decisions to perform emergency department procedures. Malpractice fear
      markedly decreases interns' enjoyment of medicine, but this effect decreases by
      residency completion.

PMID- 17446195
TI  - Variation in ancillary testing among pediatric asthma patients seen in emergency
      departments.
AB  - BACKGROUND: Variation in the management of acute pediatric asthma within
      emergency departments is largely unexplored. OBJECTIVES: To investigate whether
      ancillary testing for patients with asthma would be associated with patient,
      physician, and hospital characteristics. METHODS: The authors performed an
      analysis of a subset of patients from an extensive retrospective chart review of
      randomly selected charts at all 25 member emergency departments of the Pediatric
      Emergency Care Applied Research Network. Patients with a diagnosis of asthma were
      selected for supplemental review and included in this study. Ancillary tests
      analyzed were chest radiographs and selected blood tests. Hierarchical analyses
      were performed to describe the associations between ancillary testing and the
      variables of interest. RESULTS: A total of 12,744 chart abstractions were
      completed, of which 734 (6%) were patients with acute exacerbations of asthma.
      Overall, 302 patients with asthma (41%) had ancillary testing. Of the 734
      patients with asthma, 198 (27%) had chest radiographs and 104 (14%) had blood
      tests. Chest radiographs were more likely to be ordered in patients with fever.
      Less blood testing was associated with physician subspecialty training in
      pediatric emergency medicine, patients treated at children's hospitals, higher
      patient oxygen saturation, and patient disposition to home. CONCLUSIONS:
      Ancillary testing occurred in more than one third of children with asthma, with
      chest radiographs ordered most frequently. Efforts to reduce the use of chest
      radiographs should target the management of febrile patients with asthma, whereas
      efforts to reduce blood testing should target providers without subspecialty
      training in pediatric emergency medicine and patients treated in nonchildren's
      hospitals who are more ill.

PMID- 17446196
TI  - Assessment of teacher interruptions on learners during oral case presentations.
AB  - BACKGROUND: Studies have only recently begun to investigate the effects of
      interruptions on physicians in the emergency department (ED). OBJECTIVES: To
      determine the frequency and nature of interruptions by the training physician
      that occur when medical trainees do oral case presentations (OCPs) in the ED.
      METHODS: This was an observational study. Learner OCPs to attending emergency
      physicians were observed in the ED of an urban Level 1 trauma center at a major
      teaching hospital. A single investigator followed attending physicians blinded to
      the study objective in a nonrandomized convenience sampling of all ED shifts,
      recording information regarding teacher interruptions during new patient
      presentations. Learners completed a brief questionnaire after each OCP. RESULTS:
      A total of 196 OCPs were observed. The mean (+/-SD) duration of OCPs was 3.30 (+/
      1.85) minutes, and the mean (+/-SD) number of interruptions was 0.75 (+/-0.60)
      per minute and 2.49 (+/-1.95) per OCP. The number of interruptions (per OCP) and
      duration of OCP varied by learner level of training, with more experienced
      learners giving shorter presentations and being interrupted less often. Frequency
      (per minute) of interruptions did not vary by learner level. In 40.3% of OCPs,
      attending physicians interrupted to give an assessment and/or a plan before the
      learner had done so, but 8.3% of interrupted learners believed that teacher
      interruptions were "disruptive" to their OCP. CONCLUSIONS: Attending emergency
      physicians frequently interrupt learners during new patient OCPs, with the number
      of interruptions varying by learner level of training. Teacher interruptions
      appear to have minimal, if any, detrimental effect on the perceived effectiveness
      of OCPs as a learning experience.

PMID- 17446197
TI  - The presence of B-type natriuretic peptide in burns and the responsiveness of
      fibroblasts to BNP: proof of principle.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) released from cardiac myocytes plays
      an important role in cardiac homeostasis through cyclic guanosine monophosphate
      (cGMP) activation. BNP also reduces cardiac remodeling and fibrosis. The
      antifibrotic effects of BNP are mediated in part by blocking the effects of
      transforming growth factor beta, a profibrotic cytokine that plays a significant
      role in cutaneous wound healing. It is unclear if BNP plays any role in cutaneous
      wound healing. OBJECTIVES: To investigate if BNP levels would be elevated in
      thermally injured human skin and if human-derived fibroblasts would respond to
      BNP exposure by increasing levels of cGMP. METHODS: This was an in vitro analysis
      of human skin. Skin samples and cells were collected from patients with and
      without thermal injury. The authors stained three skin samples from normal skin
      (taken at the time of elective cosmetic surgery) with antibodies to BNP and
      compared these with three tissue samples obtained from burned human skin taken
      during tangential excision of deep burns. Normal human-derived fibroblasts and
      keratinocytes were exposed in triplicate to BNP in vitro, and cGMP accumulation
      was evaluated. Levels of cGMP were quantified and compared with analysis of
      variance. RESULTS: BNP was present in all specimens of thermally injured skin
      (especially around collagen, epithelial cells, and endothelial cells) but not in
      any uninjured skin samples (p = 0.05, single-tailed Fisher's exact test). In
      vitro grown fibroblasts showed significant increases of cGMP levels with
      increasing levels of BNP exposure (mean [+/-SD]: 0.6 [+/-0.3], 1.2 [+/-0.2], 4.6
      [+/-0.1], and 5.0 [+/-0.9] pmol/mL with BNP concentrations of 0, 10, 500, and
      1,000 nmol/L, respectively; p < 0.001). The effect of BNP on keratinocytes was
      minimal and below the level of quantification. CONCLUSIONS: These findings
      demonstrate proof of principle that human fibroblasts are responsive to the
      effects of BNP in vitro and that BNP is present in injured skin, suggesting that
      BNP may play a role in cutaneous wound healing.

PMID- 17446198
TI  - Urticaria and angio-oedema due to ziprasidone.
AB  - Antipsychotic medications are commonLy associated with adverse cutaneous
      reactions (ACRs) in approximately 5% of patients. Angio-oedema accompanying
      urticaria is one of the most serious ACRs. The 36-year-old female patient who was
      diagnosed with ;Paranoid schizophrenia' 6 years ago, was commenced on ziprasidone
      120 mg/day. On day 30 of the treatment, the patient presented urticarial papules
      and plaques all over the body and angio-oedema in the face. The patient was
      diagnosed as ;Urticaria + Angio-oedema'. The development of ACRs after the
      initation of ziprasidone monotherapy, disappearance of lesions after the
      discontinuation of this antipsychotic, and positive intradermal skin test all
      suggests a possible causal relationship between ACRs and ziprasidone. To our
      knowledge, this is the first reported case of urticaria and angio-oedema due to
      ziprasidone monotherapy. Ziprasidone is a valid and effective choice amongst
      antipsychotic medications, but this case calls for caution regarding ACRs at the
      time of prescribing.

PMID- 17446200
TI  - An investigation of the subjective experiences of sex after alcohol or drug
      intoxication.
AB  - Despite long-standing concern over the sexual health of the population there has
      been little work undertaken in the UK investigating sexual risk taking and sexual
      behaviours in the context of substance use. To investigate this further, 270 non
      drug treatment seeking members of the public aged between 18 and 66 were
      administered a questionnaire containing the Alcohol Use Disorders Identification
      Test (AUDIT), the Drug Abuse Screening Test (DAST), the Severity of Dependence
      Scale (SDS), the Sexual Risks Scale and Attitudes toward condom use (SRSA), the
      Sexual Sensation Seeking Scale (SSSS); the Hospital Anxiety and Depression Scale
      (HADS), and questions pertaining to sexual episodes proximal to substance use.
      The population reported a varied history of substances and despite there not
      being self-awareness of problematic drug use, 39.4% reported above the cut-off
      mark of six on the DAST. An even greater percentage (57.8%) reported a score
      above eight on the AUDIT indicating hazardous or harmful drinking behaviour. The
      substance most often associated with sexual episodes was alcohol, followed by
      cannabis and ecstasy, and all were most frequently consumed in private houses.
      Sexual activity after drug use was most frequently circumstantial (i.e. the
      individual hadn't taken the substance for the specific purposes of sex), and was
      significantly associated with use of cannabis and ecstasy. The second most
      frequently reported association between drug use and sex was facilitation of a
      sexual encounter (i.e. to lower sexual inhibitions, increase self esteem and
      confidence), which was associated with use of alcohol, cannabis, cocaine and
      ecstasy. Although it was not possible to identify differences in subjective
      sexual changes after use of particular drugs, subjects reported that compared to
      sex after alcohol, sex on other drugs was more pleasurable and satisfying, with a
      greater perception of interpersonal contact with the partner and a greater
      willingness to sexually experiment. However, this latter change was not
      associated with changes in the type of sexual activity engaged in. Regression
      analysis revealed that the greatest subjective changes in sexual experiences were
      reported by younger participants who had ingested either ecstasy or cannabis
      prior to the sexual episode. These results are discussed in the context of sexual
      risk taking and suggest areas of intervention focus which may address substance
      use and sexual risk taking together.

PMID- 17446201
TI  - Review: Serotonin by stress interaction: a susceptibility factor for the
      development of depression?
AB  - A genetic predisposition to depression may be a potential risk factor in the
      development of depression. Although the neurobiological equivalent of the
      predisposition remains unclear, it seems as though the brain serotonin (5-HT)
      system plays an important mediating role. Therefore, individuals with a family
      history of depression (FH+) may be more likely to develop depression due to an
      innate vulnerability related to altered serotonergic neurotransmission in the
      brain. A major problem, however, is that the role of brain 5-HT in depression is
      complex and this serotonin-related innate vulnerability, by itself, is not
      sufficient enough to cause a depressive episode. In the search for additional
      factors, stress has received particular attention. Stressful life events
      influence and precede the onset of depression. Furthermore, depression is
      associated with stress hormone dysregulation and bidirectional interactions are
      thought to occur between stress-related changes in the neuroendocrine stress
      system and the 5-HT system. In the current review, we argue that healthy
      individuals with a positive family history of depression are more prone to
      develop depression due to a genetic 5-HT susceptibility, which deteriorates
      stress coping mechanisms and increases stress vulnerability.

PMID- 17446202
TI  - New onset heightened interest or drive for gambling, shopping, eating or sexual
      activity in patients with Parkinson's disease: the role of dopamine agonist
      treatment and age at motor symptoms onset.
AB  - Alterations of impulse control that have recently been associated with
      Parkinson's disease (PD) are serious behavioural disturbances with significant
      impact on PD patients and their families.A total of 193 consecutive PD patients
      with no history of psychiatric illness and 190 age/gender-matched healthy
      controls were queried on the presence of new onset heightened interest or drive
      for gambling, shopping, eating or sexual activity (GSES). Clinical data were
      retrieved from medical charts and interviews. logistic regressions models
      assessed risk factors for these specific troublesome behaviours. New or
      heightened interests or drives for GSES behaviours were reported by 27 patients
      (14% vs 0% for controls). Younger age at PD motor symptoms onset (OR = 0.99, p =
      0.0172), male gender (OR = 1.10, p = 0.0576) and longer duration of treatment
      with dopamine agonists (DAs)(OR = 1.18, >/=6 years versus never treated, p =
      0.0459) contributed additively to the risk of developing one or more of these
      behavioural features. New onset heightened interests or drives for GSES are not
      rare behavioural disturbances among patients with PD. Age, gender and duration of
      treatment with DAs have an independent and additive effect on the risk to develop
      such behavioural changes. Patients should be informed about potential treatment
      associated behavioural changes.

PMID- 17446203
TI  - Psychotropic drug prescribing in child and adolescent learning disability
      psychiatry.
AB  - This postal questionnaire study investigated the prescribing practices of a group
      of senior British psychiatrists who have responsibilities for children and
      adolescents with learning disabilities (mental retardation). The study revealed
      that all of the clinicians surveyed (n = 16) were prescribing psychotropic
      medication; psychostimulants and major tranquillizers represented the most
      frequently prescribed classes and, respectively, methylphenidate, risperidone,
      melatonin, sodium valproate and carbamazepine were the most frequently employed
      specific agents. Most patients were receiving monotherapy. Many (14/16)
      clinicians reported difficulties in shared-care prescribing arrangements with
      General Practitioners. The study concludes that psychopharmacology is an
      established part of the psychiatric management of learning disabled children but
      acknowledges the need for the elaboration of clinical governance standards to
      this area of practice.

PMID- 17446204
TI  - Charles Bonnet Syndrome: successful treatment of visual hallucinations due to
      vision loss with selective serotonin reuptake inhibitors.
AB  - Visual hallucinations are a common and often distressing consequence of vision
      loss, particularly in age-related macular degeneration. Charles Bonnet Syndrome
      (CBS) is defined by the triad of complex visual hallucinations, ocular pathology
      causing visual deterioration and preserved cognitive status. So far, although
      this condition is frequent, no established treatment for CBS has been stated. We
      report here the case of a 78-year-old woman, who came in our hospital because of
      a 4-week long mild depressive symptomatology. For 1 year she experienced daily
      sudden, unexpected, vivid and elaborate hallucinations. Insight was completely
      present, so the patient stated that the hallucinations were unreal and that the
      faces, geometrical figures and animals she saw every day were possibly due to her
      vision loss. The Mini Mental State Examination, digit span and verbal fluency
      were administered and no cognitive impairment was reported. The visual acuity was
      hand motion. After 4 days of treatment with venlafaxine the hallucinations
      completely disappeared. This is the first case to show that selective serotonin
      (and noradrenalin) reuptake inhibitors may be an effective and well-tolerated
      treatment for visual hallucinations associated with vision loss, and it adds to
      evidence implicating serotonergic pathways in the pathogenesis of visual
      hallucinations.

PMID- 17446205
TI  - Effects of alpha-lactalbumin on emotional processing in healthy women.
AB  - The synthesis of serotonin (5-HT) in the central nervous system is dependent on
      the availability to the brain of its precursor amino acid, tryptophan (TRP).
      Recent studies suggest that alpha-lactalbumin, a whey-derived protein with a
      relatively high TRP content, increases plasma TRP and produces endocrine and
      cognitive changes consistent with facilitation of brain 5-HT function. In the
      present study we assessed the biochemical and cognitive effects of alpha
      lactalbumin (40 g) in 28 healthy female subjects in a parallel group, placebo
      controlled design. Relative to a casein-derived control protein, alpha
      lactalbumin increased plasma TRP and the ratio of TRP to neutral amino acids.
      However, there was no effect on salivary cortisol secretion or tasks of emotional
      processing shown previously to be sensitive to pharmacological manipulation of 5
      HT in healthy volunteers. The results suggest that alpha-lactalbumin produces a
      relatively modest increase in TRP availability which may not be sufficient to
      produce the changes in emotional processing seen with administration of pure TRP
      in healthy subjects. Further studies in subjects more vulnerable to stress are
      needed to assess the potential therapeutic effects of alpha-lactalbumin in
      clinical populations.

PMID- 17446206
TI  - Atomoxetine increases salivary cortisol in healthy volunteers.
AB  - It has been proposed that acute hypothalamo-pituitary-adrenal (HPA) axis
      challenge using noradrenergic drugs may be of utility in assessing the functional
      integrity of central noradrenaline pathways. Atomoxetine (formerly tomoxetine) is
      a highly selective noradrenaline reuptake inhibitor, which has recently been
      licensed for the treatment of attention deficit hyperactivity disorder (ADHD).
      The aim of this study was to assess the effects of acute atomoxetine on salivary
      cortisol levels for the first time.A total of 60 healthy male volunteers received
      60 mg atomoxetine, 30 mg citalopram, or placebo per os in a double-blind parallel
      groups design (n = 20 per group). Salivary cortisol, blood pressure and pulse
      rates were recorded at baseline and at +1.0, +1.5, +2.5 and +3.5 hours after
      capsule administration.60 mg atomoxetine led to highly significant increases in
      salivary cortisol and a moderate increase in pulse rate, in the absence of
      significant effects on blood pressure. 30 mg citalopram had no significant
      effects on cortisol or cardiovascular parameters. These data support the utility
      of atomoxetine neuroendocrine challenge for evaluating central noradrenaline
      pathways, which may be of future use in neuropsychiatric patient studies.
      Furthermore, the effects of atomoxetine on HPA axis function may have clinical
      implications given the use of this agent in the treatment of ADHD.

PMID- 17446207
TI  - Protein kinase C delta stimulates antigen presentation by Class II MHC in murine
      dendritic cells.
AB  - Maturation of dendritic cells (DCs) regulates protein sorting in endosomal
      compartments to promote the surface expression of molecules involved in T cell
      activation. MHC Class II complexes are mobilized to the surface via intracellular
      effector molecules that remain largely unknown. We here show that protein kinase
      C (PKC) stimulates Class II antigen surface expression, using knock-in mice that
      express a Class II-green fluorescent protein fusion protein as a read out.
      Selective inhibition of PKCdelta counteracts the ability of DCs to stimulate
      Class II MHC-restricted antigen-specific T cells. Activation of PKC does not
      affect antigen uptake, peptide loading and surface display of Class I MHC and
      transferrin receptor in DCs. We show that activation-induced Class II MHC surface
      expression is dependent on activation of PKCdelta and conclude that this event is
      pivotal for optimal CD4 T cell activation.

PMID- 17446208
TI  - Single-molecule microscopy reveals heterogeneous dynamics of lipid raft
      components upon TCR engagement.
AB  - The existence of lipid rafts and their importance for immunoreceptor signaling is
      highly debated. By non-invasive single molecule imaging, we analyzed the dynamics
      of the T-cell antigen receptor (TCR), the lipid raft-associated
      glycosylphosphatidylinositol (GPI) proteins CD48 and CD59 and the major leukocyte
      phosphatase CD45 in living naive T lymphocytes. TCR triggering induced the
      immobilization of CD45 and CD48 at different positions within the T-cell
      interface. The second GPI protein, CD59, did not co-immobilize indicating lipid
      raft heterogeneity in living T lymphocytes. A novel biochemical approach
      confirmed that lipid raft components are not associated in the plasma membrane of
      resting cells, and variably associate with specific receptors to distinct lipid
      rafts upon activation.

PMID- 17446209
TI  - Preferential recognition of a microbial metabolite by human Vgamma2Vdelta2 T
      cells.
AB  - Human Vgamma2Vdelta2 T cells are stimulated by prenyl pyrophosphates, such as
      isopentenyl pyrophosphate (IPP), and play important roles in mediating immunity
      against microbial pathogens and have potent anti-tumor activity. (E)-4-hydroxy-3
      methyl-but-2-enyl pyrophosphate (HMBPP) has been identified as a metabolite in
      the 2-C-methyl-D-erythritol-4 phosphate (MEP) pathway for isoprenoid biosynthesis
      that is used by many bacteria and protozoan parasites. We find that HMBPP is the
      major Vgamma2Vdelta2 T-cell antigen for many bacteria, including Mycobacterium
      tuberculosis, Yersinia enterocolitica and Escherichia coli. HMBPP was a 30 000
      fold more potent antigen than IPP. Using mutant bacteria, we show that bacterial
      antigen levels for Vgamma2Vdelta2 T cells are controlled by MEP pathway enzymes
      and find no evidence for the production of 3-formyl-1-butyl pyrophosphate.
      Moreover, HMBPP reactivity required only germ line-encoded Vgamma2Vdelta2 TCR
      elements and is present at birth. Importantly, we show that bacterial HMBPP
      levels correlated with their ability to expand Vgamma2Vdelta2 T cells in vivo
      upon engraftment into severe combined immunodeficiency-beige mice. Thus, the
      production of HMBPP by a microbial-specific isoprenoid pathway plays a major role
      in determining whether bacteria will stimulate Vgamma2Vdelta2 T cells in vivo.
      This preferential stimulation by a common microbial isoprenoid metabolite allows
      Vgamma2Vdelta2 T cells to respond to a broad array of pathogens using this
      pathway.

PMID- 17446210
TI  - Influenza A virus elevates active cathepsin B in primary murine DC.
AB  - Dendritic cells (DCs) act as a first-line recognition system for invading
      pathogens, such as influenza A. The interaction of DC with influenza A virus
      results in DC activation via endosomal Toll-like receptors and also leads to
      presentation of viral peptides on MHC class II molecules. Prior work demonstrated
      that influenza A virus (A/HKx31; H3N2) infection of BALB/c mice activates lung
      DCs for antigen presentation, and that the enhanced function of these cells
      persists long after viral clearance and resolution of the virus-induced
      inflammatory response. Whether influenza A virus has acute or longer-lasting
      effects on the endo/lysosomal antigen-processing machinery of DCs has not been
      studied. Here, we show that antigen presentation from intact protein antigen, but
      not peptide presentation, results in increased T cell stimulation by influenza
      exposed lung DCs, suggesting increased antigen processing/loading in these DCs.
      We find that cathepsin (Cat) B levels and activity are substantially up-regulated
      in murine lung DCs, harvested 30 days after A/HKx31 infection. CatB levels and
      activity are also increased in murine splenic and bone marrow-derived DCs,
      following short-term in vitro exposure to UV-inactivated influenza A virus.
      Modest effects on CatX are also seen during in vivo and in vitro exposure to
      influenza A virus. Using a cell permeable Cat inhibitor, we show Cats in
      influenza-exposed DCs to be functional and required for generation of a T cell
      epitope from intact ovalbumin. Our findings indicate that influenza A virus
      affects the MHC class II antigen-processing pathway, an essential pathway for
      CD4(+) T cell activation.

PMID- 17446211
TI  - Differential expression of Toll-like receptors in murine peritoneal macrophages
      in vitro on treatment with cisplatin.
AB  - In the present study, we have investigated the differential expression of Toll
      like receptors [(TLRs) 1-9] in murine peritoneal macrophages in vitro, on
      treatment with cis-diaminedichloroplatinum (II) (cisplatin). It is demonstrated
      that cisplatin induces the expression of TLRs and is a potent activator of Toll
      signaling pathway. The enhanced expression of TLR2, -3, -4, -5, -6, -7, -8 and -9
      is observed at different time intervals after 5 microg ml(-1) cisplatin
      treatment. The expression of downstream signaling molecules of TLR-signaling
      pathway--myeloid differentiation factor 88, IRAK1, tumor necrosis factor receptor
      associated factor 6 and transcription factors IRF3 and nuclear factor-kappaB (NF
      kappaB)--has also been investigated. The expression of TLR2, -3, -4 and -9 was
      down-regulated in cisplatin-treated macrophages in the presence of inhibitors of
      mitogen-activated protein kinases and NF-kappaB pathways, suggesting a role of
      these pathways in cisplatin-induced TLR expression. It is also observed that pre
      treatment of macrophages with cisplatin and subsequent incubation with TLR
      ligands significantly enhanced the production of pro-inflammatory cytokines
      (tumor necrosis factor-alpha, IFN-gamma, IL-1beta and IL-12) and iNOS expression
      in macrophages. The data suggest that treatment of macrophages with cisplatin
      renders them more susceptible to subsequent induction of pro-inflammatory
      cytokines and iNOS expression by different TLR ligands. It is proposed that the
      pharmacological reagents like cisplatin can be used to manipulate the innate
      immune responses, which may be effectively used for the development of novel
      therapeutic approaches.

PMID- 17446212
TI  - Requirements for CD4(+) T cell levels in acute Mycobacterium bovis strain bacille
      Calmette Guerin (BCG)-induced granulomas differ for optimal mycobacterial control
      versus granuloma formation.
AB  - Bacille Calmette Guerin (BCG)-induced granulomas contain T cells that express a
      broad TCR repertoire even at the level of the individual lesion. We have
      developed a BCG infection model in mice having only one T cell specific for a
      recombinant BCG epitope expressed in a lipoprotein fusion protein. Here we report
      that the single T cell model induces well-formed granulomas, but has weaker
      protection than that conferred by wild-type granulomas. This finding correlates
      with lower CD4(+) T cell recruitment into acute granulomas (3 weeks post
      infection). Chronic granulomas (6 weeks post infection) contain similar
      proportions of CD4(+) T cells in both models, but in the single T cell model the
      proportion of leukocyte function-associated antigen-1 low, non-IFNgamma-producing
      CD4(+) T cells is lower. In fact, even though it is likely that there are very
      few, if any, IFNgamma(+) CD4(+) T cells present in the single T cell model,
      granuloma integrity is not influenced, indicating that high levels of IFNgamma
      are not required for granuloma maintenance. These data underline the importance
      of early CD4(+) T cell recruitment into the granuloma to anti-mycobacterial
      protection and show that CD4(+) T cell levels required for granuloma formation
      and optimal protection are different. These data also show that T cell repertoire
      complexity contributes to protection against mycobacteria.

PMID- 17446213
TI  - The 14-bp deletion polymorphism in the HLA-G gene displays significant
      differences between ulcerative colitis and Crohn's disease and is associated with
      ileocecal resection in Crohn's disease.
AB  - HLA-G is a non-classical MHC class Ib molecule predominantly expressed in
      cytotrophoblasts and under pathological conditions also in chronically inflamed
      and in malignant tissues. Recently an increased expression of HLA-G was found in
      ulcerative colitis (UC), but not in Crohn's disease (CD). The HLA-G gene is
      located in IBD3, a linkage region for inflammatory bowel disease (IBD). A 14-bp
      deletion polymorphism (Del+/Del-) within exon 8 of the HLA-G gene might influence
      transcription activity and is therefore of potential functional relevance. To
      investigate whether the 14-bp deletion polymorphism is associated with IBD, 371
      patients with CD, 257 patients with UC and 739 controls were genotyped. The
      heterozygous genotype (P = 0.031) and the Del+ phenotype (P = 0.038) were
      significantly increased, whereas the homozygous Del- phenotype (P = 0.038) was
      significantly decreased in UC when compared with CD. Thus, the 14-bp deletion
      polymorphism within the HLA-G gene displayed significant differences between UC
      and CD. Moreover, a significant increase of the Del+ allele (P = 0.002) and the
      Del+/Del+ genotype (P = 0.013) and a consecutive decrease of the Del-/- genotype
      (P = 0.024) were observed in those CD cases positive for ileocecal resection.
      Thus, a potential effect of the HLA-G gene in IBD may affect both UC and CD.
      Other polymorphisms linked to the 14-bp deletion polymorphism might also
      contribute to immunopathogenesis. As there are several partly functional
      polymorphisms within the promoter region potentially influencing HLA-G
      expression, further studies in IBD are necessary in the context of differential
      expression of HLA-G between UC and CD.

PMID- 17446216
TI  - Muscle cell volume and pH changes due to glycolytic ATP synthesis.

PMID- 17446214
TI  - Inspiratory bursts in the preBotzinger complex depend on a calcium-activated non
      specific cation current linked to glutamate receptors in neonatal mice.
AB  - Inspiratory neurons of the preBotzinger complex (preBotC) form local excitatory
      networks and display 10-30 mV transient depolarizations, dubbed inspiratory drive
      potentials, with superimposed spiking. AMPA receptors are critical for
      rhythmogenesis under normal conditions in vitro but whether other postsynaptic
      mechanisms contribute to drive potential generation remains unknown. We examined
      synaptic and intrinsic membrane properties that generate inspiratory drive
      potentials in preBotC neurons using neonatal mouse medullary slice preparations
      that generate respiratory rhythm. We found that NMDA receptors, group I
      metabotropic glutamate receptors (mGluRs), but not group II mGluRs, contributed
      to inspiratory drive potentials. Subtype 1 of the group I mGluR family (mGluR1)
      probably regulates a K+ channel, whereas mGluR5 operates via an inositol 1,4,5
      trisphosphate (IP3) receptor-dependent mechanism to augment drive potential
      generation. We tested for and verified the presence of a Ca2+-activated non
      specific cation current (I(CAN)) in preBotC neurons. We also found that high
      concentrations of intracellular BAPTA, a high-affinity Ca2+ chelator, and the
      I(CAN) antagonist flufenamic acid (FFA) decreased the magnitude of drive
      potentials. We conclude that I(CAN) underlies robust inspiratory drive potentials
      in preBotC neurons, and is only fully evoked by ionotropic and metabotropic
      glutamatergic synaptic inputs, i.e. by network activity.

PMID- 17446217
TI  - Pacemaking, arrhythmias, inotropy and hypertrophy: the many possible facets of
      IP3 signalling in cardiac myocytes.

PMID- 17446218
TI  - Ricardo Miledi and the foundations of synaptic and extra-synaptic
      neurotransmitter receptor physiology.

PMID- 17446219
TI  - Activation of AMP kinase alpha1 subunit induces aortic vasorelaxation in mice.
AB  - Vasodilatation is a vital mechanism of systemic blood flow regulation that occurs
      during periods of increased energy demand. The AMP-dependent protein kinase
      (AMPK) is a serine/threonine kinase that is activated by conditions that increase
      the AMP-to-ATP ratio, such as exercise and metabolic stress. We hypothesized that
      AMPK could trigger vasodilatation and participate in blood flow regulation. Rings
      of thoracic aorta were isolated from C57Bl6 mice and mice deficient in the AMPK
      catalytic alpha1 (AMPKalpha1-/-) or alpha2 (AMPKalpha2-/-) subunit and their
      littermate controls, and mounted in an organ bath. Aortas were preconstricted
      with phenylephrine (1 microM) and activation of AMPK was induced by addition of
      increasing concentrations of 5-aminoimidazole-4-carboxamide-1-beta-D
      ribofuranoside (AICAR). AICAR (0.1-3 mM) dose-dependently induced relaxation of
      precontracted C57BL6, AMPKalpha1+/+ and alpha2+/+ aorta (P<0.001, n=5-7 per
      group). This AICAR induced vasorelaxation was not inhibited by the addition of
      adenosine receptor antagonists. Moreover, when aortic rings were freed of
      endothelium by gentle rubbing, AICAR still induced aortic ring relaxation,
      suggesting a direct effect of AICAR on smooth muscle cells. When aortic rings
      were pretreated with L-NMMA (30 microM) to inhibit nitric oxide synthase
      activity, AICAR still induced relaxation. Western blot analysis of C57Bl6 mice
      denuded aorta showed that AMPK was phosphorylated after incubation with AICAR and
      that AMPKalpha1 was the main catalytic subunit expressed. Finally, AICAR-induced
      relaxation of aortic rings was completely abolished in AMPKalpha1-/- but not
      AMPKalpha2-/- mice. Taken together, the results show that activation of
      AMPKalpha1 but not AMPKalpha2 is able to induce aortic relaxation in mice, in an
      endothelium- and eNOS-independent manner.

PMID- 17446220
TI  - The effects of repeated exposure to hypercapnia on arousal and cardiorespiratory
      responses during sleep in lambs.
AB  - Arousal and cardio-respiratory responses to respiratory stimuli during sleep are
      important protective mechanisms that rapidly become depressed in the active sleep
      state when episodes of hypoxia or asphyxia are repeated: whether responses to
      repeated hypercapnia are similarly depressed is not known. This study aimed to
      determine if arousal and cardio-respiratory responses also become depressed with
      repeated episodes of hypercapnia during sleep and whether responses differ in
      active sleep and quiet sleep. Eight newborn lambs were instrumented to record
      sleep state and cardio-respiratory variables. Lambs were subjected to two
      successive 12 h sleep recordings, assigned as either sequential control and test
      days, or test and control days performed between 12.00 and 00.00 h. The control
      day was a baseline study in which the lambs breathed air to determine spontaneous
      arousal probability. During the test day, lambs were exposed to a 60 s episode of
      normoxic hypercapnia (Fractional inspired CO2 (F(ICO2)) = 0.08 and Fractional
      inspired O2(F(IO2)) = 0.21 in N2) during every quiet sleep and active sleep
      epoch. The probability of lambs arousing during the hypercapnic exposure exceeded
      the probability of spontaneous arousal during quiet sleep (58% versus 21%, chi2 =
      54.0, P < 0.001) and active sleep (39% versus 20%, chi2 = 10.0, P < 0.01), though
      the response was less in active sleep. Exposure to hypercapnia also resulted in a
      significant increase in ventilation in quiet sleep (150 +/- 22%) and active sleep
      (97 +/- 23%, P < 0.05), though the increase was smaller in active sleep (P <
      0.05). Small (< 5%) blood pressure increases and heart rate decreases were
      evident during hypercapnia in quiet sleep, but not in active sleep. Arousal and
      cardio-respiratory responses persisted with repetition of the hypercapnic
      exposure. In summary, although arousal and cardio-respiratory responses to
      hypercapnia are less in active sleep compared with quiet sleep, these protective
      responses are not diminished with repeated exposure to hypercapnia.

PMID- 17446221
TI  - Characterization of the molecular and electrophysiological properties of the T
      type calcium channel in human myometrium.
AB  - Rises in intracellular calcium are essential for contraction of human myometrial
      smooth muscle (HMSM) and hence parturition. The T-type calcium channel may play a
      role in this process. The aim was to investigate the role of the T-type calcium
      channel in HMSM by characterizing mRNA expression, protein localization,
      electrophysiological properties and function of the channel subunits
      Cav3.1(alpha1G), Cav3.2(alpha1H), and Cav3.3(alpha1I). QRT-PCR,
      immunohistochemistry, electrophysiology and invitro contractility were performed
      on human myometrial samples from term, preterm, labour and not in labour. QRT-PCR
      analysis of Cav3.1, Cav3.2 and Cav3.3 demonstrated expression of Cav3.1 and
      Cav3.2 with no significant change (P>0.05) associated with gestation or labour
      status. Immunohistochemistry localized Cav3.1 to myometrial and vascular smooth
      muscle cells whilst Cav3.2 localized to vascular endothelial cells and invading
      leucocytes. Voltage clamp studies demonstrated a T-type current in 55% of cells.
      Nickel block of T-type current was voltage sensitive (IC50 of 118.57+/-68.9
      microM at -30 mV). Activation and inactivation curves of ICa currents in cells
      expressing T-type channels overlapped demonstrating steady state window currents
      at the resting membrane potential of myometrium at term. Current clamp analysis
      demonstrated that hyperpolarizing pulses to a membrane potential greater than -80
      mV elicited rebound calcium spikes that were blocked reversibly by 100 microM
      nickel. Contractility studies demonstrated a reversible decrease in contraction
      frequency during application of 100 microM nickel (P<0.05). We conclude that the
      primary T-type subunit expressed in some MSMCs is Cav3.1. We found that
      application of 100 microM nickel to spontaneously contracting human myometrium
      reversibly slows contraction frequency.

PMID- 17446222
TI  - Feedforward versus feedback modulation of human vestibular-evoked balance
      responses by visual self-motion information.
AB  - Visual information modulates the balance response evoked by a pure vestibular
      perturbation (galvanic vestibular stimulation, GVS). Here we investigate two
      competing hypotheses underlying this visual-vestibular interaction. One
      hypothesis assumes vision acts in a feedforward manner by altering the weight of
      the vestibular channel of balance control. The other assumes vision acts in a
      feedback manner through shifts in the retinal image produced by the primary
      response. In the first experiment we demonstrate a phenomenon that is predicted
      by both hypotheses: the GVS-evoked balance response becomes progressively smaller
      as the amount of visual self-motion information is increased. In the second
      experiment we independently vary the pre-stimulus and post-stimulus visual
      environments. The rationale is that feedback effects would depend only upon the
      post-stimulus visual environment. Although the post-stimulus visual environment
      did affect later parts of the response (after approximately 400 ms), the pre
      stimulus visual environment had a strong influence on the size of the early part
      of the response. We conclude that both feedforward and feedback mechanisms act in
      concert to modulate the GVS-evoked response. We suggest this dual interaction
      that we observe between visual and vestibular channels is likely to apply to all
      sensory channels that contribute to balance control.

PMID- 17446223
TI  - Control of basal extracellular adenosine concentration in rat cerebellum.
AB  - To re-examine how the basal extracellular concentration of adenosine is regulated
      in acutely isolated cerebellar slices we have combined electrophysiological and
      microelectrode biosensor measurements. In almost all cases, synaptic transmission
      was tonically inhibited by adenosine acting via A1 receptors. By contrast, in
      most slices, the biosensors did not measure an adenosine tone but did record a
      spatially non-uniform extracellular tone of the downstream metabolites (inosine
      and hypoxanthine). Most of the extracellular hypoxanthine arose from the
      metabolism of inosine by ecto-purine nucleoside phosphorylase (PNP). Adenosine
      kinase was the major determinant of adenosine levels, as its inhibition increased
      both adenosine concentration and A1 receptor-mediated synaptic inhibition.
      Breakdown of adenosine by adenosine deaminase was the major source of the
      inosine/hypoxanthine tone. However adenosine deaminase played a minor role in
      determining the level of adenosine at synapses, suggesting a distal location.
      Blockade of adenosine transport (by NBTI/dipyridamole) had inconsistent effects
      on basal levels of adenosine and synaptic transmission. Unexpectedly, application
      of NBTI/dipyridamole prevented the efflux of adenosine resulting from block of
      adenosine kinase at only a subset of synapses. We conclude that there is spatial
      variation in the functional expression of NBTI/dipyridamole-sensitive
      transporters. The increased spatial and temporal resolution of the purine
      biosensor measurements has revealed the complexity of the control of adenosine
      and purine tone in the cerebellum.

PMID- 17446224
TI  - NMDA receptors in preBotzinger complex neurons can drive respiratory rhythm
      independent of AMPA receptors.
AB  - The role of AMPA receptors (AMPARs) in generation and propagation of respiratory
      rhythm is well documented both in vivo and in vitro, whereas the functional
      significance of NMDA receptors (NMDARs) in preBotzinger complex (preBotC) neurons
      has not been explored. Here we examined the interactions between AMPARs and
      NMDARs during spontaneous respiratory rhythm generation in slices from neonatal
      rats in vitro. We tested the hypothesis that activation of NMDARs can drive
      respiratory rhythm in the absence of other excitatory drives. Blockade of NMDARs
      with dizocilpine hydrogen maleate (MK-801, 20 microM) had a negligible effect on
      respiratory rhythm and pattern under standard conditions in vitro, whereas
      blockade of AMPARs with NBQX (0.5 microM) completely abolished respiratory
      activity. Removal of extracellular Mg2+ to relieve the voltage-dependent block of
      NMDARs maintained respiratory rhythm without a significant effect on period, even
      in the presence of high NBQX concentrations (<or= 100 microM). Removal of Mg2+
      increased inspiratory-modulated inward current peak (I(I)) and charge (Q(I)) in
      preBotC neurons voltage-clamped at -60 mV by 245% and 309%, respectively, with
      respect to basal values. We conclude that the normal AMPAR-mediated postsynaptic
      current underlying respiratory drive can be replaced by NMDAR-mediated
      postsynaptic current when the voltage-dependent Mg2+ block is removed. Under this
      condition, respiratory-related frequency is unaffected by changes in I(I),
      suggesting that the two can be independently regulated.

PMID- 17446225
TI  - Prospective targeting and control of end-tidal CO2 and O2 concentrations.
AB  - Current methods of forcing end-tidal PCO2 (PETCO2) and PO2 (PETO2) rely on breath
      by-breath adjustment of inspired gas concentrations using feedback loop
      algorithms. Such servo-control mechanisms are complex because they have to
      anticipate and compensate for the respiratory response to a given inspiratory gas
      concentration on a breath-by-breath basis. In this paper, we introduce a low gas
      flow method to prospectively target and control PETCO2 and PETO2 independent of
      each other and of minute ventilation in spontaneously breathing humans. We used
      the method to change PETCO2 from control (40 mmHg for PETCO2 and 100 mmHg for
      PETO2) to two target PETCO2 values (45 and 50 mmHg) at iso-oxia (100 mmHg), PETO2
      to two target values (200 and 300 mmHg) at normocapnia (40 mmHg), and PETCO2 with
      PETO2 simultaneously to the same targets (45 with 200 mmHg and 50 with 300 mmHg).
      After each targeted value, PETCO2 and PETO2 were returned to control values. Each
      state was maintained for 30 s. The average difference between target and measured
      values for PETCO2 was +/-1 mmHg, and for PETO2 was +/-4 mmHg. PETCO2 varied by +/
      1 mmHg and PETO2 by +/-5.6 mmHg (s.d.) over the 30 s stages. This degree of
      control was obtained despite considerable variability in minute ventilation
      between subjects (+/-7.6 l min(-1)). We conclude that targeted end-tidal gas
      concentrations can be attained in spontaneously breathing subjects using this
      prospective, feed-forward, low gas flow system.

PMID- 17446227
TI  - Low-grade inflammation and hypoadiponectinaemia have an additive detrimental
      effect on aortic stiffness in essential hypertensive patients.
AB  - AIMS: In this study, we investigated the combined effect of increased high
      sensitivity C-reactive protein (hs-C-reactive protein) and hypoadiponectinaemia
      on aortic stiffness in essential hypertensive subjects. METHODS AND RESULTS: A
      total of 267 untreated patients with stage I-II essential hypertension underwent
      ambulatory BP and carotid-femoral pulse wave velocity (c-f PWV) evaluation. The
      distributions of hs-C-reactive protein and adiponectin were split by the median
      (1.3 mg/L and 7.8 microg/mL, respectively) and accordingly subjects were
      stratified into those with high and low values. Patients with high (n = 134)
      compared with those with low hs-C-reactive protein (n = 133) values exhibited
      greater c-f PWV levels (by 0.8 m/s, P < 0.0001), whereas patients with low (n =
      133) compared with those with high (n = 134) adiponectin levels had higher c-f
      PWV (by 0.9 m/s, P < 0.0001). Stepwise regression analysis revealed that age, 24
      h systolic BP, hs-C-reactive protein and adiponectin were independent predictors
      of arterial stiffness. In patients with low hs-C-reactive protein,
      hypoadiponectinaemia (n = 46) compared with high adiponectin (n = 87) was
      accompanied by increased c-f PWV (by 0.8 m/s, P < 0.0001). Similarly in patients
      with high hs-C-reactive protein, hypoadiponectinaemia (n = 84) compared with high
      adiponectin (n = 50) was related to heightened c-f PWV (by 0.7 m/s, P = 0.008).
      CONCLUSION: In essential hypertension, pronounced low-grade inflammation in
      conjunction with hypoadiponectinaemia exerts an additive detrimental effect on
      aortic stiffness, accelerating the vascular ageing process.

PMID- 17446228
TI  - Safety and efficacy concerns regarding elective coronary artery surgery in
      patients with prior coronary stents.

PMID- 17446226
TI  - Modulation of multisegmental monosynaptic responses in a variety of leg muscles
      during walking and running in humans.
AB  - Motor responses evoked by stimulating the spinal cord percutaneously between the
      T11 and T12 spinous processes were studied in eight human subjects during walking
      and running. Stimulation elicited responses bilaterally in the biceps femoris,
      vastus lateralis, rectus femoris, medial gastrocnemius, soleus, tibialis
      anterior, extensor digitorum brevis and flexor digitorum brevis. The evoked
      responses were consistent with activation of Ia afferent fibres through
      monosynaptic neural circuits since they were inhibited when a prior stimulus was
      given and during tendon vibration. Furthermore, the soleus motor responses were
      inhibited during the swing phase of walking as observed for the soleus H-reflex
      elicited by tibial nerve stimulation. Due to the anatomical site and the fibre
      composition of the peripheral nerves it is difficult to elicit H-reflex in leg
      muscles other than the soleus, especially during movement. In turn, the
      multisegmental monosynaptic responses (MMR) technique provides the opportunity to
      study modulation of monosynaptic reflexes for multiple muscles simultaneously.
      Phase-dependent modulation of the MMR amplitude throughout the duration of the
      gait cycle period was observed in all muscles studied. The MMR amplitude was
      large when the muscle was activated whereas it was generally reduced, or even
      suppressed, when the muscle was quiescent. However, during running, there was a
      systematic anticipatory increase in the amplitude of the MMR at the end of swing
      in all proximal and distal extensor muscles. The present findings therefore
      suggest that there is a general control scheme by which the transmission in the
      monosynaptic neural circuits is modulated in all leg muscles during stepping so
      as to meet the requirement of the motor task.

PMID- 17446229
TI  - Stroke prophylaxis in patients with atrial fibrillation: what can we do about it?

PMID- 17446231
TI  - Papillary muscle inflammation in Takayasu's arteritis revealed by FDG-PET.

PMID- 17446232
TI  - Rat strain-dependent susceptibility to ischemia-induced retinopathy associated
      with retinal vascular endothelial growth factor regulation.
AB  - Vascular endothelial growth factor (VEGF) is a potent inflammation, vascular
      permeability, and angiogenic factor. Variations of the VEGF gene are implicated
      in the pathogenesis of diabetic retinopathy. Previous studies have shown that
      Brown Norway (BN) rats have higher retinal VEGF levels and more severe retinal
      vascular leakage than Sprague-Dawley (SD) rats in response to ischemia and
      diabetes. To investigate the molecular mechanism of vascular leakage in this
      animal model, F2 progeny were generated by crossbreeding BN and SD rats. Neonatal
      rats were exposed to hyperoxia to induce oxygen-induced retinopathy (OIR) models.
      The F2 rats in response to ischemia have shown a linear distribution of retinal
      VEGF levels, which is significantly and positively correlated to retinal vascular
      leakage. We identified a single nucleotide polymorphism (SNP) at upstream
      stimulating factor-binding site in the VEGF promoter region between BN and SD
      rats. No differences were found in retinal vascular permeability or VEGF levels
      between F2 rats with BN, SD, and BN/SD alleles of VEGF SNP. The increased retinal
      VEGF levels are correlated to ischemia-induced retinal vascular leakage in the
      OIR rat model. The VEGF mRNA and promoter are not responsible for increased
      retinal VEGF level and vascular permeability. The up-regulation of VEGF
      expression activated by a yet to be identified upstream factor or mediator
      affecting VEGF stability may be associated with a high susceptibility to retinal
      vascular leakage in BN rats.

PMID- 17446233
TI  - Larval zebrafish as a model for glucose metabolism: expression of
      phosphoenolpyruvate carboxykinase as a marker for exposure to anti-diabetic
      compounds.
AB  - The zebrafish model system is one of the most widely used animal models for
      developmental research and it is now becoming an attractive model for drug
      discovery and toxicological screening. The completion of sequencing the zebrafish
      genome and the availability of full-length cDNAs and DNA microarrays for
      expression analysis, in addition to techniques for generating transgenic lines
      and targeted mutations, have made the zebrafish model even more attractive to
      researchers. Recent data indicate that the regulation of glucose metabolism in
      zebrafish, through the production of insulin, is similar to mammalian models, and
      many of the genes involved in regulating blood glucose levels have been
      identified in zebrafish. The data presented here show that adult zebrafish
      respond to anti-diabetic drugs similarly to mammalian models, by reducing blood
      glucose levels. Furthermore, we show that the expression of phosphoenolpyruvate
      carboxykinase (PEPCK), which catalyzes a rate-limiting step in gluconeogenesis
      and is transcriptionally regulated by glucagon and insulin, is regulated in
      larval zebrafish similarly to that seen in mammalian systems, and changes in
      PEPCK expression can be obtained through real-time PCR analysis of whole larval
      RNA. Taken together, these data suggest that larval zebrafish may be an
      appropriate model for the examination of glucose metabolism, using PEPCK as an
      indicator of blood glucose levels.

PMID- 17446234
TI  - Separate and synergistic effect of progesterone and estradiol on induction of
      annexin 2 and its interaction protein p11 in pregnant sheep myometrium.
AB  - To search for myometrial candidate genes regulated by progesterone, we isolated
      annexin 2 cDNA by subtractive hybridization and cloning. We also examined the
      effect of estradiol and/or progesterone, individually or combined, on expressions
      of annexin 2 and its ligand protein, p11 in pregnant sheep intrauterine tissues.
      Annexin 2 is a Ca(2+)-dependent phospholipid-binding protein which interacts with
      p11 to form a bivalent heterotetramer. The heterotetramer was indicated in the
      production of prostaglandins through the regulation of cytosolic phospholipase A2
      (cPLA2) and arachidonic acid release. Thus, annexin 2 and p11 could be the
      important players in Ca(2+) signaling and prostaglandin production in uterine
      smooth muscles. Twenty-two ewes were treated with vehicle (n = 6), or 5 mg
      estradiol administered intramuscularly twice a day for 2 days (n = 6), or 100 mg
      progesterone administered intramuscularly twice a day for 14 days (n = 5), or
      estradiol plus progesterone with 100 mg progesterone administered intramuscularly
      twice a day for 10 days (n = 5) and then with vehicle for 2 days followed by
      estradiol for 2 days (5 mg administered intramuscularly twice a day). At 121 days
      of gestation age (dGA), endometrium, myometrium, placenta, and cervix were
      obtained under halothane anesthesia. Subtractive hybridization was used to
      isolate differentially expressed mRNAs from myometrial tissues treated with
      progesterone, which was confirmed by western blot at protein level. Annexin 2 and
      p11 interaction was validated by immunoprecipitation and their expressions in
      intrauterine tissues were determined by western blot analysis. Data were analyzed
      by ANOVA. A cDNA clone from myometrial-subtracted library representing
      differentially expressed mRNA in the pregnant sheep myometrium with progesterone
      treatment was identified as annexin 2 by sequence analysis and BLASTN search.
      Annexin 2 was present in both cytosolic and membrane-associated fractions of
      intrauterine tissues. In contrast, p11 was detectable only in myometrial
      cytosolic fraction. Both annexin 2 and p11 significantly increased in myometrial
      cytosolic fraction after progesterone or progesterone plus estradiol treatment.
      Furthermore, estradiol and progesterone combined had a more profound effect on
      induction of annexin 2 than progesterone alone. Annexin 2 was immunoprecipitated
      specifically by p11 antibody from the myometrium. This study indicates that
      progesterone may play an important role in the control of myometrial
      contractility by modifying protein expression associated with Ca2+ and
      prostaglandin signaling systems during pregnancy. Enhanced expression of
      myometrial annexin 2 in progesterone plus estradiol group supports our hypothesis
      that estrogen's stimulation is optimized by progesterone's priming in the
      pregnant sheep uterus.

PMID- 17446235
TI  - Assessment of the anti-obesity effects of the TNP-470 analog, CKD-732.
AB  - The systemic treatment with angiogenesis inhibitor has been shown to result in
      weight reduction and adipose tissue loss in various models of obesity. To verify
      the mechanism of CKD-732 (TNP-470 analog) against obesity, we evaluated CKD-732's
      peripheral and central anti-obesity effects. CKD-732 was injected subcutaneously
      (s.c.) for 7 days in various animal models and intracerebroventricularly (i.c.v.)
      in arcuate nucleus (ARC) lesion mice, ob/ob mice, and normal littermates.
      Modulation of the hypothalamic neuropeptide mRNAs after i.c.v. injection was
      evaluated in ARC lesion mice and normal littermates. A conditioned taste aversion
      (CTA) was performed using lithium chloride (LiCl) as a positive control agent in
      Long-Evans Tokushima Otsuka and Otsuka Long-Evans Tokushima fatty (OLETF) rats.
      As a result, 7 days of CKD-732 s.c. injection reduced the cumulative food intake
      and the body weight significantly in both treated obese (e.g. 114.8 +/- 13.4 g vs
      170.7 +/- 20.6 g, 7.9 +/- 0.5% decrease vs 0.3 +/- 2.2% decrease; in treated
      OLETF rat versus control OLETF rat, P < 0.01 respectively) and non-obese models.
      Epididymal and mesenteric fat pads, and the size of adipocytes were significantly
      decreased in treated rats. A single i.c.v. injection decreased food intake and
      body weight in ARC lesion mice and ob/ob mice but not in normal littermates.
      Unexpectedly, the hypothalamic neuropeptide mRNAs were not altered by single
      i.c.v. injection. CKD-732 also induced a dose-dependent CTA comparable with LiCl
      injection, which is a commonly used agent to produce a CTA. In conclusion, CKD
      732 causes significant body weight and appetite reduction, possibly by decreasing
      adiposity directly and inducing central anorexia, which is partly explained by a
      CTA. These results should be carefully verified to assess the utility of CKD-732
      as an anti-obesity drug.

PMID- 17446236
TI  - Dehydroepiandrosterone improves murine osteoblast growth and bone tissue
      morphometry via mitogen-activated protein kinase signaling pathway independent of
      either androgen receptor or estrogen receptor.
AB  - Dehydroepiandrosterone (DHEA) may be a promising agent for postmenopausal
      osteoporosis (PMO), but its mechanism to modulate osteoblasts (OBs) is yet to be
      explained. To elucidate the effects of DHEA treatment on the ovariectomized (OVX)
      mice and its mechanisms, we evaluated the morphology of mice bone tissue and
      expression of proliferating cell nuclear antigen (PCNA) in the vertebrae-derived
      OB after having treated the OVX animals with DHEA. The results showed that DHEA
      administration increased the expression of PCNA in OB and changed the bone tissue
      morphometry of the PMO model. To further investigate this mechanism, the OB was
      isolated from neonatal mice calvariae by the enzyme-digested assay, exposed to
      DHEA, and then analyzed for ultrastructure, DNA content, early apoptotic cells,
      and phosphorylation of extracellular signal-regulated kinase 1/2. It was found
      that DHEA promoted proliferation and inhibited apoptosis of OB significantly, via
      mitogen-activated protein kinase signaling pathway independent of either androgen
      receptor or estrogen receptor, suggesting that it may exert roles via a DHEA
      specific receptor directly, not by way of conversion to androgens or estrogens.

PMID- 17446237
TI  - Sp1 and Sp3 regulate glucokinase gene transcription in the liver of gilthead sea
      bream (Sparus aurata).
AB  - To better understand the transcriptional machinery that governs glucokinase (GCK)
      expression, we have cloned and characterized the proximal promoter region of GCK
      from gilthead sea bream (Sparus aurata). The 5'-flanking region of GCK was
      isolated by chromosome walking. SMART RACE-PCR allowed us to locate the
      transcription start site 98 bp (bp) upstream from the translational start.
      Transfection analysis in HepG2 cells revealed the presence of a functional
      promoter in the 1397 bp 5'-flanking isolated fragment (positions -1321 to +76
      relative to the transcription start site). Sequential 5'-deletion analysis
      indicated a core functional promoter for basal transcription within the 288 bp
      upstream from the transcription start site. Transient transfection experiments
      performed in HepG2 cells and electrophoretic mobility shift assays denoted that
      Sp1 binds and transactivates GCK promoter, whereas Sp3 repressed Sp1-mediated
      activation of GCK by competing for the same binding site. Mutations in the Sp
      binding site completely abolished the enhancing effect of Sp1. Treatment with
      insulin stimulated GCK expression, and increased Sp1 levels in S. aurata liver.
      We propose a new mechanism that involves Sp1 and Sp3 to mediate insulin
      activation of GCK transcription.

PMID- 17446238
TI  - Signaling mechanisms leading to regulation of proliferation and differentiation
      of the mesenchymal chondrogenic cell line RCJ3.1C5.18 in response to IGF-I.
AB  - Since IGF-I is an important chondrocyte growth factor, we sought to examine the
      intracellular mechanisms by which it exerts two of its pivotal effects,
      stimulation of proliferation and differentiation. We used the mesenchymal
      chondrogenic cell line RCJ3.1C5.18, which progresses spontaneously to
      differentiated growth plate chondrocytes. This differentiation process could be
      enhanced by exogenous IGF-I. Pharmacological inhibition of the
      phosphatidylinositol-3 (PI-3) kinase by LY294002, mitogen-activated protein
      kinase/extracellular signal-regulated kinase (MAPK/ERK)1/2 by U0126, the protein
      kinase (PK) A pathway by H-89 or KT5720, and the PKC pathway by
      bisindolylmaleimide suppressed IGF-I-stimulated cell proliferation. In contrast,
      IGF-I-enhanced early cell differentiation, as assessed by collagen type II and
      aggrecan gene expression, was not affected by MAPK/ERK1/2 pathway inhibition, but
      significantly diminished by inhibition of the PI-3 kinase, the PKC and the PKA
      pathway. Moreover, terminal differentiation of chondrocytes in response to IGF-I,
      as assessed by gene expression of alkaline phosphatase, Indian hedgehog, and
      collagen type X, were only interrupted by PI-3 kinase pathway inhibition. In
      conclusion, IGF-I exerts its differential effect on chondrocyte proliferation vs
      differentiation through the use of at least four partially interacting
      intracellular signaling pathways, whose activity is temporarily regulated. When
      chondrocytes progress from proliferating cells to early and terminal
      differentiating cells, they progressively inactivate IGF-I-related intracellular
      signaling pathways. This mechanism might be essential for the complex and cell
      stage-specific anabolic action of IGF-I in the growth plate.

PMID- 17446239
TI  - Neurovascular invasion at the osteochondral junction and in osteophytes in
      osteoarthritis.
AB  - BACKGROUND: Normal adult articular cartilage is thought to be avascular and
      aneural. OBJECTIVE: To describe neurovascular structures at the osteochondral
      junction and in osteophytes in tibiofemoral osteoarthritis (OA) displaying a
      range of severity of cartilage changes. METHODS: Articular surfaces were obtained
      from 40 patients at total knee joint replacement surgery for tibiofemoral OA
      (TKR) and seven patients post mortem (PM). Antibodies directed against CD34
      (vascular endothelium), protein gene product 9.5 (pan-neuronal marker), substance
      P and calcitonin gene-related peptide (sensory nerves) and C-flanking peptide of
      neuropeptide Y (sympathetic nerves) were used to localise blood vessels and
      nerves by immunohistochemistry. Severity of OA cartilage changes was graded
      histologically. RESULTS: TKR and PM samples displayed a range of OA cartilage
      changes including tidemark breaching by vascular channels. Sympathetic and
      sensory nerves were both present within vascular channels in the articular
      cartilage, in both mild and severe OA. Perivascular and free nerve fibres, and
      nerve trunks were observed within the subchondral bone marrow and within the
      marrow cavities of osteophytes. Sensory and sympathetic nerves displayed similar
      distributions in each region studied. CONCLUSION: Vascularisation and the
      associated innervation of articular cartilage may contribute to tibiofemoral pain
      in OA across a wide range of structural disease severity.

PMID- 17446241
TI  - Incidence of antibiotic prescribing in dental practice in Norway and its
      contribution to national consumption.
AB  - OBJECTIVES: To assess dentistry-based utilization of the 11 antibiotics
      prescribed by dentists in Norway and its relative contribution to national
      outpatient consumption and to determine the relationship between numbers of
      prescriptions and the consumption of these antibiotics. METHODS: Data on national
      antibiotic prescriptions by dentists in 2004 and 2005 were used. Consumption of
      the antibiotics was expressed using WHO defined daily doses (DDDs), DDDs per 1000
      inhabitants per day (DIDs) and numbers of prescriptions per 1000 inhabitants
      (PIDs). RESULTS: Analysis of 268,834 prescriptions issued by 4765 dentists showed
      that the dentists' prescriptions contributed 8% of the total national consumption
      of the 11 antibiotics and 13.5%, 2.8% and 1.2% of the national beta-lactam
      penicillins, macrolides and lincosamides and tetracyclines utilization,
      respectively. The dentists' contributions to the national
      phenoxymethylpenicillin, spiramycin and metronidazole consumptions were
      considerably higher (> or =13.2%) than for the other prescribed antibiotics (< or
      =8.6%). There was a strong positive correlation between numbers of DDDs and
      numbers of prescriptions and between DIDs and numbers of PIDs. CONCLUSIONS:
      Reliance of Norwegian dentists on phenoxymethylpenicillin as their first choice
      suggests a low prevalence of antibiotic resistance among oral bacteria in Norway.
      Norwegian dentists prefer to prescribe narrow-spectrum antibiotics; their
      prescribing is conservative and relatively low compared with that of physicians.

PMID- 17446242
TI  - Pharmacokinetic modelling of a once-daily dosing regimen for intravenous
      tobramycin in paediatric cystic fibrosis patients.
AB  - OBJECTIVES: This study was designed to determine an optimal dose range for the
      once-daily dosing (ODD) of tobramycin in the treatment of an acute pulmonary
      exacerbation in paediatric cystic fibrosis (CF) patients. In addition, we aimed
      to assess whether certain patient characteristics affect tobramycin
      pharmacokinetics and, therefore, dosing. METHODS: Patient characteristics and
      pharmacokinetic parameters of patients receiving tobramycin three times daily
      from 1 January 1992 to 31 October 2005 were analysed using univariate analysis
      and multiple linear regression to determine statistically significant
      relationships and to derive dosing models. The binary partitioning method was
      used to derive critical values to determine stratification within the chosen
      dosing model. RESULTS: Using multiple linear regression, age and sex were
      significantly associated with the volume of distribution divided by the body
      weight (V/kg). By the binary partitioning method, the critical value for age was
      13.75 years. CONCLUSIONS: Age and sex were used to derive an ODD regimen for
      tobramycin in paediatric CF. Using a target peak concentration range of 25-35
      mg/L, the initial dose for female CF patients at least 14 years of age was
      calculated to be 7 mg/kg/day given intravenously as a single daily dose. All
      other CF patients would receive an initial dose of 9 mg/kg/day given
      intravenously as a single daily dose. These dosing guidelines will require
      prospective evaluation for safety and efficacy.

PMID- 17446240
TI  - Standardised assessment of membrane proteinase 3 expression. Analysis in ANCA
      associated vasculitis and controls.
AB  - OBJECTIVES: Increased numbers of neutrophils expressing proteinase 3 on their
      membrane (mPR3) have been reported in anti-neutrophil cytoplasm antibody (ANCA)
      associated vasculitis (AAV) and are suggested to be involved in AAV
      immunopathogenesis. In most studies, neutrophils were analysed for mPR3
      expression without priming with TNFalpha, suggesting that mPR3 expression on
      neutrophils is dependent on other priming events, such as isolation procedures .
      These priming events can be variable. Therefore, we analysed mPR3 expression on
      neutrophils before and after priming with TNFalpha to assess whether standardised
      assessment of mPR3 expression requires priming. Using neutrophils before and
      after priming with TNFalpha, we assessed percentages of mPR3(+) neutrophils in
      patients with AAV and in disease and healthy controls. METHODS: Neutrophils from
      patients with PR3-AAV and MPO-AAV, systemic lupus erythematosus (SLE) and
      rheumatoid arthritis (RA), and from healthy controls were analysed before and
      after priming with TNFalpha for mPR3 expression. RESULTS: 42% of all individuals
      analysed showed minimal expression for mPR3 on all neutrophils before priming
      with TNFalpha, whereas after priming a clear mPR3(+) subset was observed next to
      mPR3(-) neutrophils, corresponding to bimodal mPR3 expression. In patients with
      PR3-AAV or MPO-AAV, the percentage of mPR3(+) neutrophils after priming with
      TNFalpha was significantly increased (p<0.01 and p<0.05, respectively) compared
      with healthy controls. Percentages of mPR3(+) PMN were also increased in patients
      with SLE (p<0.01) but not in RA. CONCLUSION: Standardised assessment of
      proteinase 3 on the membrane of neutrophils requires priming with TNFalpha.
      Percentages of mPR3(+) PMN are increased in AAV and SLE, but not in RA.

PMID- 17446243
TI  - A chronology of failed advocacy and frustration.

PMID- 17446244
TI  - Recruiting participants for injury studies in emergency departments.

PMID- 17446245
TI  - Policies to prevent firearm trafficking.

PMID- 17446246
TI  - Reducing firearm violence: a research agenda.
AB  - In the United States, firearms are involved in tens of thousands of deaths and
      injuries each year. The magnitude of this problem prompted the National Academy
      of Sciences (NAS) to issue a report in 2004 detailing the strengths and
      limitations of existing research on the relationship between firearms and
      violence. In response, a multidisciplinary group of experts in the field of
      firearms and violence formed the National Research Collaborative on Firearm
      Violence. The Collaborative met for 2 days in June 2005 to (1) critically review
      the main findings of the NAS report and (2) define a research agenda that could
      fill research and data gaps and inform policy that reduces gun-related crime,
      deaths and injuries. This article summarizes the Collaborative's conclusions and
      identifies priorities for research and funding.

PMID- 17446247
TI  - Challenges of recruiting farm injury study participants through hospital
      emergency departments.
AB  - BACKGROUND: Hospital emergency departments are common recruitment sites for
      injury studies. Yet recruitment method details, capture rates and response
      fractions are not consistently reported. As privacy legislation increasingly
      impinges on research activity, these parameters become even more important. The
      authors describe their experience with recruitment via emergency departments and
      outline subsequent adjustments to the recruitment approach. METHODS: The FIRM
      study was an Australian case-control study of serious farm work-related injury.
      Cases were identified prospectively by hospital staff on presentation to
      emergency departments. Consistent with the Victorian Health Records Act,
      potential cases were initially approached by hospital staff, and full recruitment
      was subsequently undertaken by study staff. Manual hospital record audits were
      conducted at five recruitment sites to determine the proportion of eligible cases
      approached. RESULTS: Among 660 medical records audited, 19 eligible cases were
      confirmed, 9 of whom were approached by hospital staff (47%, 95% CI 25 to 70%).
      In response, an additional process was established to capture missed cases, who
      were sent a letter from the hospital providing the opportunity to opt out of
      telephone contact by study staff. Early indications were that 34% (41/122) of
      missed cases actively declined to be contacted. Among those who were contacted
      and eligible, 84% (21/25) agree to study participation. CONCLUSIONS: Recruitment
      of injury research participants via hospital emergency departments is
      challenging, particularly where authorities require an intermediary to make the
      initial contact. Removal of some constraints imposed by privacy legislation would
      considerably simplify recruitment and enhance scientific rigour in conducting
      epidemiological research.

PMID- 17446248
TI  - "Risk Watch": cluster randomised controlled trial evaluating an injury prevention
      program.
AB  - OBJECTIVE: to evaluate the effectiveness of a school-based injury prevention
      program. DESIGN: Cluster randomised controlled trial. SETTING: 20 primary schools
      in Nottingham, UK. PARTICIPANTS: 459 children aged 7 to 10 years. INTERVENTION:
      The "Risk Watch" program delivered by teachers, aimed at improving bike and
      pedestrian, falls, poisoning and fire and burns safety. MAIN OUTCOME MEASURES:
      Safety knowledge, observed safety skills and self-reported safety behaviour.
      RESULTS: At follow-up, intervention group children correctly answered more fire
      and burn prevention knowledge questions than control group children (difference
      between means 7.0% (95% CI 1.5% to 12.6%)). Children in intervention group
      schools were more likely to know the correct actions to take if clothes catch
      fire and the correct way to wear a cycle helmet (difference between school means
      35.3% (95% CI 22.7% to 47.9%) and 6.3% (95% CI 1.4% to 11.1%) respectively). They
      were also more likely to know the correct actions to take in a house fire and on
      finding tablets (OR 2.80 (95% CI 1.08 to 7.22) and OR 3.50 (95% CI 1.18 to 10.38)
      respectively) and correctly demonstrated more safety skills than control group
      children (difference between means 11.9% (95% CI 1.4% to 22.5%)). There was
      little evidence to suggest the first year of the program impacted on self
      reported safety behaviours. CONCLUSIONS: The Risk Watch program delivered by
      teachers in primary schools increased some aspects of children's safety knowledge
      and skills and primary schools should consider delivering this program. Longer
      term, larger scale evaluations are required to examine retention of knowledge and
      skills and impact on safety behaviours and child injury rates.

PMID- 17446249
TI  - Pediatricians' involvement in gun injury prevention.
AB  - BACKGROUND: Injuries from small arms are of concern internationally. The health
      perspective is an emerging aspect of international work to reduce these injuries.
      This aspect has been evident in US firearm injury prevention work for over a
      decade, exhibited by strong statements from the American Academy of Pediatrics
      (AAP) to remove firearms from children's environments. OBJECTIVES: To assess
      trends among US pediatricians related to firearm injury prevention counseling
      practices and attitudes toward gun legislation. DESIGN: National random sample,
      mailed surveys of AAP members: (1) 1994 (response rate = 68.9%, n = 982); (2)
      2000 (response rate = 62.4%, n = 922). chi(2) Tests were used to assess bivariate
      relationships and logistic regression to assess multivariate relationships
      regarding counseling practices. RESULTS: Respondents in both years believed that
      violence prevention should be a priority for pediatricians (91.4% and 92.0%) and
      reported always or sometimes recommending handgun removal from the home (46.2%
      and 55.9%, respectively). In 2000, 74% of the respondents were comfortable
      discussing firearm safety; fewer thought they had sufficient training (32.7%) or
      time (27.5%) to discuss firearms. In 1994 and 2000, the likelihood of counseling
      on handgun removal was positively related to recent experience treating a gun
      injury, female sex and not owning a gun. In both years, >80% of pediatricians
      thought that gun control legislation or regulations would reduce injury and
      death. CONCLUSIONS: US pediatricians continue to adopt policies promoting gun
      injury prevention. The practices and attitudes of pediatricians may be important
      for public education strategies regarding firearm injury prevention in the US and
      internationally.

PMID- 17446250
TI  - A risky treat: exploring parental perceptions of the barriers to seating their
      children in the rear seats of passenger vehicles.
AB  - BACKGROUND: Sitting in the rear seat of a vehicle rather than in the front seat
      reduces children's risk of injury or death by > or =35% in the event of a crash.
      As road trauma is a leading cause of child morbidity and mortality in highly
      motorised nations, even in countries where restraint use is high, encouraging
      parents to place children in the rear seats of vehicles offers a low-cost avenue
      to improving children's overall health. However, little is known about the
      factors that affect parents' decisions about seating positions. OBJECTIVE: To
      explore parental perceptions of barriers to placing their children in the rear
      seat of passenger vehicles whenever possible. DESIGN AND SUBJECTS: Focus group
      discussions were held with urban parent-drivers to elicit their concerns about
      children's car safety and barriers to rear-seat use. RESULTS: Most parents had a
      rule that children should sit in the rear seat. Parents said that they relaxed
      these rules for a variety of reasons including social pressure, perceptions of
      the trip as short and because children regard sitting in the front seat as a
      treat. Parenting style, child cooperativeness, social pressure and inability to
      justify the risk of injury were identified as barriers to rear-seat travel.
      CONCLUSIONS: Effective interventions to increase the proportion of children
      travelling in the rear seat should address parents' experiences of pressure to
      relax seating rules and risk perception, as well as provide strategies that
      support sound parental safety decisions.

PMID- 17446251
TI  - Newspaper coverage of residential fires: an opportunity for prevention
      communication.
AB  - BACKGROUND: Worldwide, fire-related burns are a major cause of unintentional
      injury, morbidity and mortality, with the majority of deaths occurring in
      developing countries. In the US, as in other countries, most fatal fires occur in
      the home. Effective prevention strategies for residential fires are, however,
      currently underutilized. The news media is one available communication channel to
      promote such strategies, and analyzing current news coverage is a first step
      towards incorporating media advocacy into injury prevention efforts related to
      residential fires. METHODS: Four daily newspapers circulating widely in Maryland
      were monitored for 1 year. Articles describing residential fires were coded for
      measures of prominence, content and frame. Analysis focused on measures of issue
      newsworthiness, reporting of causation and consequences of fires, and inclusion
      of public health context and conveyance of prevention messages. RESULTS: The data
      indicate that fires are newsworthy, with 374 relevant news articles in a 1-year
      period, 32% of which appear on the first page of a section. Coverage generally
      concerned recent local fire events. Most articles discussed the consequences of
      fires (88%), and identified a causal factor (58%). Only 36%, however, included
      prevention information, and less than one-quarter set residential fires in a
      public health context. CONCLUSION: The newsworthiness of residential fires
      provides a clear opportunity for widespread communication around injury
      prevention. Improving media advocacy will entail framing discussion of recent
      fire events in such a way as to support inclusion of prevention strategies and a
      public health context in news coverage.

PMID- 17446252
TI  - Non-fatal injuries among urban and rural residents: the National Health Interview
      Survey, 1997-2001.
AB  - OBJECTIVE: Although death rates from injuries are higher in rural areas compared
      with large metropolitan areas, little is known about how non-fatal injury rates
      vary by rurality. Data from the 1997-2001 US National Health Interview Surveys
      were used to explore associations between rurality and non-fatal injury. DESIGN:
      A nationally representative survey. METHODS: The annual injury rates per 1000
      adults and 95% CIs were computed for medically attended injuries. Counties of
      residence were coded according to urban influence codes into four categories:
      large urban, small urban, suburban and rural. A linear-by-linear trend test was
      used to determine whether injury rates increase monotonically with county
      rurality. Logistic regression was used to control potential confounders. RESULTS:
      Compared with large urban counties, small urban counties experienced 8% higher
      injury odds (95% CI 1% to 15%); suburban counties 20% higher injury odds (95% CI
      10% to 31%); and rural counties 30% higher injury odds (95% CI 17% to 43%) after
      adjusting for age, gender, marital status, education and health insurance.
      CONCLUSIONS: Rural residents had higher non-fatal injury rates than urban and
      suburban residents. Exploring this discrepancy can further contribute to new
      hypotheses regarding rural injury risk and ultimately lead to better suited
      interventions for rural residents.

PMID- 17446253
TI  - Water safety: age-specific changes in knowledge and attitudes following a school
      based intervention.
AB  - OBJECTIVES: To explore whether an intervention during mandatory schooling can
      lead to age-specific changes in water safety knowledge and attitudes. METHODS:
      Age-specific questionnaires were distributed to 202 kindergarten and grade one
      pupils, 220 elementary school pupils and 337 pupils attending the first three
      high school grades in Greater Athens. The information was used to design an
      educational package that was subsequently presented to pupils of the same grades
      and similar socio-demographic profiles attending different schools in the same
      area. One month later, a post-exposure evaluation was conducted using the initial
      questionnaires, in which 115, 205 and 321 pupils from the respective grade
      categories provided their responses. In order to compare the performance of
      pupils exposed to the educational intervention with that of pupils who
      participated only in the initial assessment, mean differences in scores measuring
      overall knowledge and attitudes were estimated within each of the three grade
      groups adjusting for age, gender, sibship size, maternal education and swimming
      knowledge. RESULTS: Among kindergarten and grade one pupils, those who received
      the intervention scored significantly higher for knowledge (17.40%, 95% CI 6.41%
      to 28.39%) and attitudes (23.64%, 95% CI 4.48% to 42.79%). Among elementary
      school pupils the gains in knowledge were less evident (14.58%, 95% CI -3.05% to
      32.21%)) and almost null in attitudes (5.64%, 95% CI -11.47% to 22.77%). Further
      advancement of age showed no improvement in knowledge (-0.15%, 95% CI -5.30% to
      4.99%) and a minimal, insignificant increase in attitudes (6.32%, 95% CI -1.87%
      to 14.52%) among exposed high school pupils. CONCLUSION: The school-based
      intervention resulted in considerable positive changes in knowledge and attitudes
      among very young pupils. Elementary schooling seems to provide meagre
      opportunities to simply improve knowledge. Alternative/complementary approaches
      should be sought in any attempt to modify behavior.

PMID- 17446254
TI  - How exposure information can enhance our understanding of child traffic "death
      leagues".
AB  - OBJECTIVES: To explore whether population-based fatality rates and measures of
      traffic exposure can be combined to provide a more comprehensive measure of
      safety. To illustrate how this could be achieved using surveys from a range of
      Organisation for Economic Cooperation and Development (OECD) countries. To
      discuss why exposure is important. DESIGN AND SETTING: Fatality data were
      obtained from the International Road Traffic and Accident Database and travel
      data from surveys among government transport administrations in each country.
      METHODS: Comparable exposure data were obtained for children aged 10-14 years
      from the UK, the USA, Germany, The Netherlands, Norway, Sweden, Switzerland and
      New Zealand. Fatality rates for children travelling as pedestrians, cyclists and
      car occupants were calculated based on (1) per head of population and (2) a
      combination of rate per head population and per kilometre travelled. RESULTS: In
      this study, exposure-based fatality rates suggest a more polarized distribution
      rather than a graduated league. The USA and the UK were at the lower end of the
      table for child pedestrian safety; Germany for car-occupant safety, Sweden and
      New Zealand performed less well. For cycling, the inclusion of exposure data
      considerably changes positions within the table. Countries with higher cycling
      levels like The Netherlands perform better than those with low levels like the UK
      and New Zealand. CONCLUSIONS: Exposure-based fatality rates can help us to
      understand whether policies reduce exposure or whether they increase safety,
      given a similar level of exposure. Data need to be harmonized across OECD
      countries for a better understanding of the risks and links between health and
      sustainable travel.

PMID- 17446255
TI  - US data show sharply rising drug-induced death rates.
AB  - Substantial numbers of deaths are related to disease and injury resulting from
      the use of drugs, alcohol and firearms worldwide. Death rates associated with
      these exposures were compared with those from motor vehicle crashes in the US
      from 1979 to 2003 by race. Among Caucasians, drug-induced death rates rose
      sharply after 1990 and surpassed deaths involving alcohol and firearms in 2001
      and 2002, respectively. Among African-Americans, drug-induced deaths surpassed
      alcohol-induced deaths for the first time in 1999.

PMID- 17446256
TI  - The challenge of cross-cultural collaborative research: lessons learnt from a
      pilot case-crossover study of severe occupational hand trauma in the People's
      Republic of China.
AB  - OBJECTIVE: A pilot epidemiologic study was conducted in the People's Republic of
      China to assess the feasibility of applying the study protocol from a US case
      crossover study on transient work-related exposures and the risk of an acute
      occupational hand injury. DESIGN: Injured workers were recruited from a hand
      surgery center in Ningbo, Zhejiang, People's Republic of China. A structured face
      to-face interview questionnaire was administered. RESULTS: 156 workers with hand
      injury completed the study (73% men). The enrollment rate was 91%. Of those who
      refused participation, most indicated their reluctance was due to the requirement
      to sign the written consent form. Considerable variability was found among
      interviewers in ascertaining responses from participants to important exposure
      questions (21.3% v 97%). CONCLUSIONS: Recommendations include the following: (1)
      exploring effective oral-consent protocols that reduce participant concern and
      still meet human participant protection requirements; (2) using non-physician
      interviewers; and (3) increasing the intensity and standardization of interviewer
      training.

PMID- 17446257
TI  - Bunk bed-related injuries sustained by young children treated in emergency
      departments in the United States, 2001-2004, National Electronic Injury
      Surveillance System - All Injury Program.
AB  - OBJECTIVE: To characterize children's bunk bed-related injuries. METHODS: Data
      are from the 2001-2004 National Electronic Injury Surveillance System - All
      Injury Program. Cases were defined as children aged 0-9 years treated for a non
      fatal, unintentional injury related to a bunk bed. RESULTS: An estimated 23 000
      children aged 0-9 years were treated annually in emergency departments for bunk
      bed fall-related injuries, including 14 600 children aged <6 years. Overall, 3.2%
      were hospitalized. The injuries sustained were largely fractures, lacerations,
      contusions and abrasions, and internal injuries, with 25.2% injured in a fall
      from the top bunk. The most commonly injured body region was the head and neck.
      CONCLUSIONS: Strategies are needed to reduce the most serious injuries. Bunk beds
      should meet CPSC standards, and the youngest children should not sleep or play in
      the upper bunk or on ladders. Making care givers aware of the risks, and
      modifying the living environment are essential.

PMID- 17446258
TI  - Cochrane corner: prevention of injuries at home.

PMID- 17446259
TI  - The connexin31 F137L mutant mouse as a model for the human skin disease
      erythrokeratodermia variabilis (EKV).
AB  - Erythrokeratodermia variabilis (EKV) is a rare autosomal dominant human
      genodermatosis. Its clinical appearance varies from transient, fast moving
      erythemas to persistent brown hyperkeratoses. So far, several mutations in the
      Cx31 or Cx30.3 gene have been reported to cause EKV in humans. We have generated
      a conditional mouse mutant that carries the human F137L mutation in the Cx31 gene
      which was described to act in a transdominant negative manner. The phenylalanine
      residue at position 137 is highly conserved in several human and mouse connexin
      genes. Mouse embryonic stem (ES) cells expressing one allele of the Cx31F137L
      mutation were stable but showed approximately 30% decreased transfer of
      neurobiotin. This is probably due to dominant negative effects of the Cx31F137L
      protein on wild type Cx31 and Cx43 protein expressed in ES cells. Surprisingly,
      the healing process of tail incision wounds in Cx31(+/F137L) mice was shortened
      by 1 day, i.e. very similar as previously reported for mice with decreased
      expression of Cx43 in the epidermis. This suggests again that Cx31 and Cx43
      proteins functionally interact, possibly by forming heteromeric channels in the
      epidermis. Heterozygous Cx31(+/F137L) mice are viable and fertile, in contrast to
      homozygous Cx31(F137L/F137L) mice that die around ED 7.5. In Cx31(+/F137L) mice,
      the epidermal expression pattern and level of Cx26, Cx30, Cx30.3 and Cx43
      proteins were not altered compared with wild-type mice. No erythemas were
      detected in young C31(+/F137L) mice before 2 weeks of age. In contrast to human
      EKV patients, hyperproliferation of the stratum germinativum was found in only 5%
      of the analyzed skin area.

PMID- 17446260
TI  - Leukotriene B4 triggers release of the cathelicidin LL-37 from human neutrophils:
      novel lipid-peptide interactions in innate immune responses.
AB  - In humans, the antimicrobial peptide LL-37 and the potent chemotactic lipid
      leukotriene B4 (LTB4) are important mediators of innate immunity and host
      defense. Here we show that LTB4, at very low (1 nM) concentrations, strongly
      promotes release of LL-37 peptides from human neutrophils (PMNs) in a time- and
      dose-dependent manner, as determined by Western blot, enzyme-linked immunoassay
      (ELISA), and antibacterial activity. The LTB4-induced LL-37 release is mediated
      by the BLT1 receptor, and protein phosphatase-1 (PP-1) inhibits the release by
      suppressing the BLT1-mediated exocytosis of PMN granules. Conversely, LL-37
      elicits translocation of 5-lipoxygenase (5-LO) from the cytosol to the
      perinuclear membrane in PMNs and promotes the synthesis and release of LTB4,
      particularly from cells primed with LPS or GM-CSF. Furthermore, LL-37 stimulates
      PMN phagocytosis of Escherichia coli particles, a functional response that is
      enhanced by LTB4, especially in GM-CSF pretreated cells. In these cells, LL-37
      also enhances LTB4-induced phagocytosis. Hence, in human PMNs, positive feedback
      circuits exist between LL-37 and LTB4 that reciprocally stimulate the release of
      these mediators with the potential for synergistic bioactions and enhanced immune
      responses. Moreover, these novel lipid-peptide signaling pathways may offer new
      opportunities for pharmacological intervention and treatment of chronic
      inflammatory diseases.

PMID- 17446261
TI  - Predominant contribution of UDP-glucuronosyltransferase 2B7 in the
      glucuronidation of racemic flurbiprofen in the human liver.
AB  - Flurbiprofen is a nonsteroidal anti-inflammatory drug used as a racemic mixture.
      Although glucuronidation is one of its elimination pathways, the role of UDP
      glucuronosyltransferase (UGT) in this process remains to be investigated. Thus,
      the kinetics of the stereoselective glucuronidation of racemic (R,S)-flurbiprofen
      by recombinant UGT isozymes and human liver microsomes (HLMs) were investigated,
      and the major human UGT isozymes involved were identified. UGT1A1, 1A3, 1A9, 2B4,
      and 2B7 showed glucuronidation activity for both (R)- and (S)-glucuronide, with
      UGT2B7 possessing the highest activity. UGT2B7 formed the (R)-glucuronide at a
      rate 2.8-fold higher than that for (S)-glucuronide, whereas the other UGTs had
      similar formation rates. The glucuronidation of racemic flurbiprofen by HLMs also
      resulted in the formation of (R)-glucuronide as the dominant form, which occurred
      to a degree similar to that by recombinant UGT2B7 (2.1 versus 2.8). The formation
      of (R)-glucuronide correlated significantly with morphine 3-OH glucuronidation (r
      = 0.96, p < 0.0001), morphine 6-OH glucuronidation (r = 0.91, p < 0.0001), and 3'
      azido-3'-deoxythymidine glucuronidation (r = 0.85, p < 0.0001), a reaction
      catalyzed mainly by UGT2B7, in individual HLMs. In addition, the formation of
      both glucuronides correlated significantly (r = 0.99, p < 0.0001). Mefenamic acid
      inhibited the formation of both (R)- and (S)-glucuronide in HLMs with similar
      IC(50) values (2.0 and 1.7 muM, respectively), which are close to those in
      recombinant UGT2B7. In conclusion, these findings suggest that the formation of
      (R)- and (S)-glucuronide from racemic flurbiprofen is catalyzed by the same UGT
      isozyme, namely UGT2B7.

PMID- 17446263
TI  - Isolation and characterization of polyspecific mouse organic solute carrier
      protein 1 (mOscp1).
AB  - We succeeded in isolating the cDNA-encoding mouse organic solute carrier protein
      1 (mOscp1) from a mouse testis cDNA library. mOscp1 consisted of 1137 base pairs
      that encoded a 379-amino acid protein, and the amino acid sequence was 85%
      identical to that of human OSCP1 (hOSCP1). Northern blot analysis revealed that
      the gene coding for mOscp1 is highly expressed in the testis, but not in other
      tissues. When expressed in Xenopus laevis oocytes, mOscp1 mediated the high
      affinity transport of p-aminohippurate (PAH) (K(m) = 18.8 +/- 4.1 microM) with
      Na(+) independence. mOscp1 transported various kinds of structurally dissimilar
      drugs and chemicals such as probenecid, dehydroepiandrosterone sulfate, and
      glutarate with some differences in substrate specificity compared with hOSCP1.
      Cyclophosphamide inhibited the mOscp1-mediated PAH uptake. Immunohistochemical
      analysis revealed that the mOscp1 protein is localized in the plasma membrane
      side of Sertoli cells in the testis. Our results indicate that isolated mOscp1 is
      a polyspecific organic solute carrier protein and may be a key molecule for the
      testicular handling of organic solutes.

PMID- 17446262
TI  - CYP2C9 protein interactions with cytochrome b(5): effects on the coupling of
      catalysis.
AB  - The hemoprotein cytochrome b(5) (cyt b5) has been demonstrated to affect the
      kinetics of drug oxidation by the microsomal cytochromes P450 (P450s). However,
      the mechanisms through which cyt b5 exerts these effects are variable and P450
      isoform-dependent. Whereas the effects of cyt b5 on the major drug-metabolizing
      enzymes CYP2D6, CYP2E1, and CYP3A4 are well studied, fewer studies conducted over
      limited ranges of cyt b5 concentrations have been performed on CYP2C9. In the
      present study with CYP2C9, cyt b5 exerted complex actions upon P450 oxidative
      reactions by affecting the rate of metabolite formation, the consumption of NADPH
      by cytochrome P450 reductase, and uncoupling of the reaction cycle to hydrogen
      peroxide and water. Cytochrome b(5) devoid of the heme moiety (apo-b5) exhibited
      effects similar to those of native cyt b5. All rates were highly dependent on the
      cyt b5 to CYP2C9 enzyme ratio, suggesting that the amount of cyt b5 present in an
      in vitro incubation is an important factor that can have an impact on the
      reliability of extrapolating in vitro generated data to predict the in vivo
      condition. The major effects of cyt b5 are hypothesized to result from a cyt b5
      induced conformational change in CYP2C9 that results in an increased collision
      frequency between the iron-oxygen species (Cpd I) and the substrate, and a
      decrease in the oxidase activity. Together, these findings suggest that cyt b5
      can alter multiple steps in the P450 catalytic cycle via complex interactions
      with P450 and P450 reductase.

PMID- 17446265
TI  - Improvement of the oral drug absorption of topotecan through the inhibition of
      intestinal xenobiotic efflux transporter, breast cancer resistance protein, by
      excipients.
AB  - Recently, breast cancer resistance protein (BCRP/ABCG2) has been shown to limit
      the oral absorption of its substrates in the intestine. The purpose of this study
      was to examine whether excipients can be used as inhibitors of BCRP, to improve
      the oral drug absorption of BCRP substrates. In wild-type mice, Pluronic P85 and
      Tween 20, given orally 15 min before topotecan administration, increased the area
      under the plasma concentration-time curve (AUC) of topotecan after oral
      administration (2.0- and 1.8-fold, respectively). In contrast, Pluronic P85 and
      Tween 20 were less effective (no significant difference) on the AUC of topotecan
      after oral administration in Bcrp (-/-) mice (1.2- and 1.2-fold, respectively).
      Pluronic P85 and Tween 20 given orally did not affect significantly the AUC of
      topotecan after intravenous administration in wild-type and Bcrp (-/-) mice.
      Moreover, we determined the mucosal-to-serosal absorptive transport of topotecan
      using everted mouse ileum. Pluronic P85 and Tween 20 significantly increased the
      intestinal absorption rate of topotecan in everted sacs from wild-type mice
      whereas, in everted sacs from Bcrp (-/-) mice, the absorption rate was 2.1-fold
      greater than that in wild-type mice, and these excipients were not significantly
      effective. There was no significant difference in the intestinal P-glycoprotein
      (P-gp) expression and serosal-to-mucosal secretory transport of rhodamine 123, a
      typical P-gp substrate. Taken together, these results suggest that Pluronic P85
      and Tween 20 can improve the oral bioavailability of BCRP substrates by
      inhibiting BCRP function in the small intestine.

PMID- 17446264
TI  - Metabolism and disposition of a selective alpha(7) nicotinic acetylcholine
      receptor agonist in humans.
AB  - The metabolism and disposition of N-(3R)-1-azabicyclo[2.2.2]oct-3-ylfuro[2,3
      c]pyridine-5-carboxamide (1), an alpha(7) nicotinic acetylcholinergic receptor
      agonist, were elucidated in humans (4 female, 4 male; all white) after an oral
      dose of [(3)H]1. Overall, 1 was well tolerated, with >94% of administered
      radioactivity excreted renally by 48 h postdose; lyophilization of all urine and
      plasma samples confirmed (3)H stability within [(3)H]1. Across genders, 1
      underwent low-to-moderate oral clearance comprising both renal (67%) and
      metabolic (33%) components, with the biotransformation of 1 occurring
      predominantly via oxidation of its furanopyridine moiety to carboxylic acid 2,
      and minimally by modification of its quinuclidine nitrogen to N-oxide 4 or N
      glucuronide M5. Experiments using human in vitro systems were undertaken to
      better understand the enzyme(s) involved in the phase 1 biotransformation
      pathways. The formation of 2 was found to be mediated by CYP2D6, a
      polymorphically expressed enzyme absent in 5 to 10% of white people, whereas the
      generation of 4 was catalyzed by CYP2D6, FAD-containing monooxygenase 1 (FMO1),
      and FMO3. It is of interest that, although no overall gender-related differences
      in excretory routes, mass recoveries, pharmacokinetics, or metabolite profiles of
      1 were evident, the observation of one of eight subjects (13%) showing disparate
      (relative to all other volunteers) systemic exposures to 1, and urinary and
      plasma quantitative profiles nearly devoid of 2 with the highest levels of 1,
      seem consistent with both the identification of CYP2D6 as the only major
      recombinant cytochrome P450 transforming 1 to 2 and the demographics of white
      CYP2D6 poor metabolizers. Data also reported herein suggest that 4 is generated
      predominantly by renal FMO1 in humans.

PMID- 17446266
TI  - In vitro metabolic characterization, phenotyping, and kinetic studies of 9cUAB30,
      a retinoid X receptor-specific retinoid.
AB  - The present study was conducted to compare the in vitro phase I and phase II
      metabolic profiles of (2E,4E,6Z,8E)-8-(3',4'-dihydro-1'(2'H)-naphthalen-1'
      ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid (9cUAB30) in human, rat, and dog
      microsomes and to characterize and identify the associated metabolic kinetics and
      specific isozymes from human liver microsomes (HLM) responsible for metabolism,
      respectively. Data from these experiments revealed that nine (M1-M9) phase I
      metabolites along with a single glucuronide conjugate were observed across the
      species investigated. With the exception of glucuronidation, no evidence of
      metabolism was detected for phase II enzymes (data not shown). Significant
      differences between species with regard to metabolic profile, stability, and
      gender were noted. For the eight phase I metabolites detected in HLM, the
      specific isozymes responsible for the biotransformations were CYP2C8, CYP2C9, and
      CYP2C19, with minor contributions from CYP1A2 and CYP2B6. For the glucuronide
      conjugate, UGT1A9 was the major catalyzing enzyme, with a minor contribution from
      UGT1A3. Kinetic analysis of eight of the detected metabolites indicated that four
      seemed to follow classical hyperbolic kinetics, whereas the remaining four showed
      evidence of either autoactivation or substrate inhibition.

PMID- 17446267
TI  - Bioactivation of nitroglycerin by ascorbate.
AB  - Bioactivation of nitroglycerin (GTN) into an activator of soluble guanylate
      cyclase (sGC) is essential for the vasorelaxant effect of the drug. Besides
      several enzymes that catalyze GTN bioactivation, the reaction with cysteine is
      the sole nonenzymatic mechanism known so far. Here we show that a reaction with
      ascorbate results in GTN bioactivation. In the absence of ascorbate, GTN did not
      affect the activity of purified sGC. However, the enzyme was activated to
      approximately 20% of maximal NO-stimulated activity by GTN in the presence of 10
      mM ascorbate with an EC(50) value of 27.3 +/- 4.9 microM GTN. The EC(50) value of
      ascorbate was 0.11 +/- 0.011 mM. Activation of sGC was sensitive to
      oxyhemoglobin, superoxide, and a heme-site enzyme inhibitor. GTN had no effect
      when ascorbate was replaced by 1000 U of superoxide dismutase per milliliter.
      Ascorbate is known to reduce inorganic nitrite to NO. In the presence of 10 mM
      ascorbate, approximately 30 microM nitrite caused the same increase in sGC
      activity as 0.3 mM GTN. Determination of ascorbate-driven 1,2- and 1,3-glycerol
      dinitrate formation indicated that a 140 nM concentration of products was
      generated from 0.3 mM GTN within 10 min, excluding nitrite as a relevant
      intermediate. Our results suggest that a reaction between GTN and ascorbate or an
      ascorbate-derived species yields an activator of sGC with NO-like chemical
      properties. This reaction may contribute to GTN bioactivation in blood vessels
      under conditions of GTN tolerance and ascorbate supplementation.

PMID- 17446268
TI  - Adrenomedullin stimulates nitric oxide production from primary rat hypothalamic
      neurons: roles of calcium and phosphatases.
AB  - Adrenomedullin (ADM) in the brain plays important roles in the maintenance of
      homeostasis. Although in vivo evidence has suggested that nitric oxide (NO)
      mediates ADM's effects in the brain, mechanisms for ADM stimulation of NO
      production in neurons have not been identified. In the present study, primary
      hypothalamic neurons were used to characterize ADM-induced NO production and to
      study the underlying mechanisms. Using Calcium Orange/4-amino-5-methylamino-2',7'
      difluorofluorescein fluorescence live cell imaging, we found that ADM (1 or 10
      nM, 5 min) significantly elevated [Ca(2+)](i) and NO production in a
      concentration-dependent manner. Ca(2+) and NO responses induced by 10 nM ADM were
      abolished by pretreatment with 50 microM 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'
      tetraacetic acid-acetoxymethyl ester (BAPTA-AM), an intracellular Ca(2+)
      chelator, or protein kinase A (PKA) inhibitors 5 microM N-[2-(p
      bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89) and 50
      microM Rp-cAMP. Furthermore, the ADM-induced NO production was significantly
      attenuated by a protein phosphatase 1/2A inhibitor, okadaic acid (OA; 0.1
      microM), or calcineurin inhibitors, tacrolimus (FK506) (1 microM) and cyclosporin
      A (CsA; 0.1 microM). Using Western blotting, we found that ADM significantly
      decreased phosphorylation of neuronal nitric-oxide synthase (nNOS) at serine 847.
      This dephosphorylation was inhibited by 0.1 microM OA, 1 microM FK506, 0.1 microM
      CsA, or 5 microM H-89, and attenuated by 50 microM BAPTA-AM. These results
      suggest that, in hypothalamic neurons, ADM elevates [Ca(2+)](i) via PKA
      associated mechanisms. The PKA/Ca(2+) cascade leads to protein phosphatase (PP)
      1/PP2A- and calcineurin-mediated dephosphorylation of nNOS. We hypothesize that
      the Ca(2+) increase and nNOS dephosphorylation contribute to activation of nNOS
      and production of NO in hypothalamic neurons.

PMID- 17446269
TI  - Activation of the angiotensin II type 1 receptor leads to movement of the sixth
      transmembrane domain: analysis by the substituted cysteine accessibility method.
AB  - The role of transmembrane domain six (TMD6) of the angiotensin II type 1
      receptor, which is predicted to undergo conformational changes after agonist
      binding, was investigated using the substituted-cysteine accessibility method.
      Each residue in the Lys240-Leu265 fragment was mutated, one at a time, to a
      cysteine. The resulting mutants were expressed in COS-7 cells, which were
      subsequently treated with the charged sulfhydryl-specific alkylating agent
      methanethiosulfonate-ethylammonium (MTSEA). This treatment led to a significant
      reduction in binding of (125)I-[Sar(1),Ile(8)]AngII to the F249C, H256C, T260C,
      and V264C mutant receptors, suggesting that these residues orient themselves
      within the water-accessible binding pocket of the AT(1) receptor. It is
      noteworthy that this pattern of acquired MTSEA sensitivity was altered for TMD6
      cysteines engineered in a constitutively active AT(1) receptor. Indeed, mutant
      F249C was insensitive to MTSEA treatment, whereas the sensitivity of mutant V264C
      decreased. Under these conditions, one other mutant, F261C, was found to be
      sensitive to MTSEA treatment. Our results suggest that constitutive activation of
      the AT(1) receptor causes TMD6 to pivot. This movement moves the top
      (extracellular side) of TMD6 toward the binding pocket and simultaneously
      distances the bottom (intracellular side) away from the binding pocket. Using
      this approach, we identified key elements within TMD6 that contribute to the
      activation of class A GPCRs through structural rearrangements.

PMID- 17446270
TI  - Epstein-Barr virus and virus human protein interaction maps.
AB  - A comprehensive mapping of interactions among Epstein-Barr virus (EBV) proteins
      and interactions of EBV proteins with human proteins should provide specific
      hypotheses and a broad perspective on EBV strategies for replication and
      persistence. Interactions of EBV proteins with each other and with human proteins
      were assessed by using a stringent high-throughput yeast two-hybrid system.
      Overall, 43 interactions between EBV proteins and 173 interactions between EBV
      and human proteins were identified. EBV-EBV and EBV-human protein interaction, or
      "interactome" maps provided a framework for hypotheses of protein function. For
      example, LF2, an EBV protein of unknown function interacted with the EBV
      immediate early R transactivator (Rta) and was found to inhibit Rta
      transactivation. From a broader perspective, EBV genes can be divided into two
      evolutionary classes, "core" genes, which are conserved across all herpesviruses
      and subfamily specific, or "noncore" genes. Our EBV-EBV interactome map is
      enriched for interactions among proteins in the same evolutionary class.
      Furthermore, human proteins targeted by EBV proteins were enriched for highly
      connected or "hub" proteins and for proteins with relatively short paths to all
      other proteins in the human interactome network. Targeting of hubs might be an
      efficient mechanism for EBV reorganization of cellular processes.

PMID- 17446271
TI  - Changes in nitrogen cycling during the past century in a northern hardwood
      forest.
AB  - Nitrogen (N) availability, defined here as the supply of N to terrestrial plants
      and soil microorganisms relative to their N demands, limits the productivity of
      many temperate zone forests and in part determines ecosystem carbon (C) content.
      Despite multidecadal monitoring of N in streams, the long-term record of N
      availability in forests of the northeastern United States is largely unknown.
      Therefore, although these forests have been receiving anthropogenic N deposition
      for the past few decades, it is still uncertain whether terrestrial N
      availability has changed during this time and, subsequently, whether forest
      ecosystems have responded to increased N deposition. Here, we used stable N
      isotopes in tree rings and lake sediments to demonstrate that N availability in a
      northeastern forest has declined over the past 75 years, likely because of
      ecosystem recovery from Euro-American land use. Forest N availability has only
      recently returned to levels forecast from presettlement trajectories, rendering
      the trajectory of future forest N cycling uncertain. Our results suggest that
      chronic disturbances caused by humans, especially logging and agriculture, are
      major drivers of terrestrial N cycling in forest ecosystems today, even a century
      after cessation.

PMID- 17446273
TI  - Subpicosecond oxygen trapping in the heme pocket of the oxygen sensor FixL
      observed by time-resolved resonance Raman spectroscopy.
AB  - Dissociation of oxygen from the heme domain of the bacterial oxygen sensor
      protein FixL constitutes the first step in hypoxia-induced signaling. In the
      present study, the photodissociation of the heme-O2 bond was used to synchronize
      this event, and time-resolved resonance Raman (TR(3)) spectroscopy with
      subpicosecond time resolution was implemented to characterize the heme
      configuration of the primary photoproduct. TR(3) measurements on heme
      oxycomplexes are highly challenging and have not yet been reported. Whereas in
      all other known six-coordinated heme protein complexes with diatomic ligands,
      including the oxymyoglobin reported here, heme iron out-of-plane motion (doming)
      occurs faster than 1 ps after iron-ligand bond breaking; surprisingly, no
      sizeable doming is observed in the oxycomplex of the Bradyrhizobium japonicum
      FixL sensor domain (FixLH). This assessment is deduced from the absence of the
      iron-histidine band around 217 cm(-1) as early as 0.5 ps. We suggest that
      efficient ultrafast oxygen rebinding to the heme occurs on the femtosecond time
      scale, thus hindering heme doming. Comparing WT oxy-FixLH, mutant proteins FixLH
      R220H and FixLH-R220Q, the respective carbonmonoxy-complexes, and oxymyoglobin,
      we show that a hydrogen bond of the terminal oxygen atom with the residue in
      position 220 is responsible for the observed behavior; in WT FixL this residue is
      arginine, crucially implicated in signal transmission. We propose that the rigid
      O2 configuration imposed by this residue, in combination with the hydrophobic and
      constrained properties of the distal cavity, keep dissociated oxygen in place.
      These results uncover the origin of the "oxygen cage" properties of this oxygen
      sensor protein.

PMID- 17446274
TI  - Thermal expansion of iron-rich alloys and implications for the Earth's core.
AB  - Understanding the thermal-chemical state of the Earth's core requires knowledge
      of the thermal expansion of iron-rich alloys at megabar pressures and high
      temperatures. Our survey of literature revealed a significant lack of such data.
      We have determined the unit-cell parameters of the iron-sulfur compound Fe(3)S by
      using synchrotron x-ray diffraction techniques and externally heated diamond
      anvil cells at pressures up to 42.5 GPa and temperatures up to 900 K. The zero
      pressure thermal expansivity of Fe(3)S is determined in the form alpha = a(1) +
      a(2)T, where a(1) = 3.0 +/- 1.3 x 10(-5) K(-1) and a(2) = 2.8 +/- 1.5 x 10(-8) K(
      2). The temperature dependence of isothermal bulk modulus ((partial
      differential)K(T,0)/(partial differential)T)(P) is estimated at -3.75 +/- 1.80 x
      10(-2) GPa K(-1). Our data at 42.5 GPa and 900 K suggest that approximately 2.1
      at. % (1.2 wt. %) sulfur produces 1% density deficit in iron. We have also
      carried out energy-dispersive x-ray diffraction measurements on pure iron and
      Fe(0.864)Si(0.136) alloy samples that were placed symmetrically in the same multi
      anvil cell assemblies, using the SPring-8 synchrotron facility in Japan. Based on
      direct comparison of unit cell volumes under presumably identical pressures and
      temperatures, our data suggest that at most 3.2 at. % (1.6 wt. %) silicon is
      needed to produce 1% density deficit with respect to pure iron.

PMID- 17446272
TI  - Protection against Escherichia coli infection by antibody to the Staphylococcus
      aureus poly-N-acetylglucosamine surface polysaccharide.
AB  - Poly-N-acetylglucosamine (PNAG) is a surface polysaccharide produced by
      Staphylococcus aureus and Staphylococcus epidermidis and is an effective target
      for opsonic and protective Ab for these two organisms. Recently, it has been
      found that Escherichia coli produces an exo-polysaccharide, designated
      polyglucosamine, that is biochemically indistinguishable from PNAG. We analyzed
      30 E. coli strains isolated from urinary tract and neonatal bloodstream
      infections for the pga locus, PNAG antigen production, and susceptibility to
      opsonic killing and protection from lethal infection by Ab to PNAG. Twenty-six of
      30 strains carried the pga locus, 25 of 30 expressed immunologically detectable
      PNAG, and 21 of 30 could be killed by rabbit IgG specific for the deacetylated
      form of the staphylococcal PNAG. Ab to staphylococcal PNAG protected mice against
      lethality from five different E. coli strains expressing PNAG. PNAG expression by
      both Gram-negative and Gram-positive organisms could make this antigen a
      conserved vaccine target for multiple pathogenic species of bacteria.

PMID- 17446275
TI  - Deterministic characterization of stochastic genetic circuits.
AB  - For cellular biochemical reaction systems where the numbers of molecules is
      small, significant noise is associated with chemical reaction events. This
      molecular noise can give rise to behavior that is very different from the
      predictions of deterministic rate equation models. Unfortunately, there are few
      analytic methods for examining the qualitative behavior of stochastic systems.
      Here we describe such a method that extends deterministic analysis to include
      leading-order corrections due to the molecular noise. The method allows the
      steady-state behavior of the stochastic model to be easily computed, facilitates
      the mapping of stability phase diagrams that include stochastic effects, and
      reveals how model parameters affect noise susceptibility in a manner not
      accessible to numerical simulation. By way of illustration we consider two
      genetic circuits: a bistable positive-feedback loop and a negative-feedback
      oscillator. We find in the positive feedback circuit that translational
      activation leads to a far more stable system than transcriptional control.
      Conversely, in a negative-feedback loop triggered by a positive-feedback switch,
      the stochasticity of transcriptional control is harnessed to generate
      reproducible oscillations.

PMID- 17446276
TI  - Evolution of antibody response and fungal antigens in the serum of a patient
      infected with Candida famata.
AB  - The presence of fungal antibodies and antigens in the serum of a patient
      diagnosed in 1996 with acute zonal occult outer retinopathy caused by Candida
      famata infection was examined. Antibodies against C. famata increased until 1999
      2000 when antifungal treatment was initiated. The antibodies were detected by
      ELISA and immunofluorescence analysis using C. famata. These antibodies were not
      immunoreactive against several Candida species tested. Positive
      immunofluorescence was obtained with IgM, but not IgA, IgG or IgE. Moreover, the
      IgM response disappeared several months after treatment with antifungal
      compounds, despite the fact that C. famata antigens were present in the blood.
      Finally, a sensitive test was developed to assay for the presence of C. famata
      antigens in serum based on the immunodetection of fungal antigens transferred to
      a nitrocellulose membrane and incubated with rabbit antibodies raised against C.
      famata. According to this method, the infection diminished with antifungal
      treatment.

PMID- 17446277
TI  - A peptide mimetic of the mycobacterial mannosylated lipoarabinomannan:
      characterization and potential applications.
AB  - Mannosylated lipoarabinomannan (ManLAM), a complex lipoglycan, is a major
      component of Mycobacterium tuberculosis, the agent of tuberculosis (TB), and is
      an antigen used for serological diagnosis of TB. Screening random phage-display
      peptide libraries with anti-ManLAM mAb CS40 for peptide epitope mimics
      (mimotopes) led to the isolation of a panel of peptides. One of these peptides
      (B11) was characterized as a ManLAM mimotope: it bound the anti-ManLAM CS40 mAb
      and competed with ManLAM for antibody binding. Mice immunized with keyhole limpet
      haemocyanin-conjugated B11 peptide in a proper adjuvant developed antibodies that
      recognized ManLAM. Competition experiments demonstrated that the B11 peptide
      inhibited binding of mAb CS40 to ManLAM in a concentration-dependent manner. The
      data indicated that the affinity of CS40 mAb to B11 (K(D) 1.33 x 10(-8)) is
      higher than its affinity to ManLAM (K(D) 3.00 x 10(-7)). The sera of TB patients,
      as well as the sera of mice experimentally infected with M. tuberculosis,
      contained significant levels of antibodies that recognized both the B11 peptide
      and ManLAM. The specificity and sensitivity of the ELISA B11-based test were
      similar to those of the ELISA ManLAM-based test, indicating that the B11 antigen
      could be a good substitute for ManLAM serology for the diagnosis of TB.

PMID- 17446278
TI  - Use of immunoblotting as an alternative method for serogrouping Leptospira.
AB  - Leptospirosis is a worldwide zoonotic disease caused by a spirochaete bacterium,
      Leptospira. Serological detection of this micro-organism basically relies on a
      conventional microscopic agglutination test (MAT), which has some limitations and
      disadvantages. In the present study, immunoblotting has been applied as an
      alternative method for differentiating serogroups and serovars of leptospires.
      Leptospiral whole-cell lysates from a total of 26 serovars were subjected to
      immunoblotting using rabbit antisera against individual serovars. The findings
      clearly demonstrated that the pattern of immunoreactive bands could be used to
      differentiate between leptospires of different serogroups, consistent with MAT
      results. There was a multi-band pattern that was unique for the pathogenic
      Leptospira antigens and was not observed in the non-pathogenic Leptospira biflexa
      and non-leptospiral bacteria (i.e. Escherichia coli, Burkholderia pseudomallei
      and Helicobacter pylori). For pathogenic Leptospira species, a prominent smear
      like band at approximately 19-30 kDa was present when the antigens were probed
      with the homologous antisera. The molecular size of the prominent band, although
      it showed a cross-reaction between members within the same serogroup, differed
      among different serovars. The results obtained from polyclonal antibodies
      (antisera) were confirmed using mAb. With its simplicity and safety of
      experimental procedures, it is proposed that immunoblotting may potentially be
      useful as an alternative method for differentiating between serogroups of
      leptospires.

PMID- 17446279
TI  - Genetically similar isolates of Klebsiella pneumoniae serotype K1 causing liver
      abscesses in three continents.
AB  - The magA gene was sought in hypermucoviscous isolates of Klebsiella spp., the
      Klebsiella K serotype reference strains and in isolates of the K1 serotype of
      Klebsiella pneumoniae from the UK, Hong Kong, Israel, Taiwan and Australia. Only
      K1 isolates were PCR positive for magA; this gene was found in all such isolates
      tested. Hypermucoviscosity was not confined to magA positive isolates, nor was it
      found in all magA positive isolates. Comparison of XbaI PFGE profiles revealed
      that most (19/23) of the magA positive isolates clustered within 72 % similarity,
      with a further subcluster of isolates, from three different continents,
      clustering within >80 %. All of the 16 isolates tested within the main cluster
      had the same sequence type (ST 23) by multilocus sequence typing, with the
      exception of one isolate, which had a single nucleotide difference at one of the
      seven loci. This study indicates that a genotype strongly associated with highly
      invasive disease in Taiwan, where large numbers of cases have been reported, is
      geographically very widespread.

PMID- 17446280
TI  - A paradigm for the molecular identification of Mycobacterium species in a routine
      diagnostic laboratory.
AB  - The aim of this study was to improve the identification of Mycobacterium species
      in the context of a UK teaching hospital. Real-time PCR assays were established
      to enable the rapid differentiation between Mycobacterium tuberculosis (MTB)
      complex and Mycobacterium species other than tuberculosis (MOTT), followed by 16S
      rRNA gene sequencing for the speciation of MOTT. Real-time PCR assays gave
      comparable results to those from the reference laboratory. The implementation of
      these PCR assays using an improved bead extraction method has enhanced the
      mycobacterial diagnostic service at the Royal Free Hospital by providing a rapid
      means of differentiating between MTB complex and MOTT, and would be simple to
      implement in similar laboratories. Sequence analysis successfully identified a
      range of Mycobacterium spp. representative of those encountered in the clinical
      setting of the authors, including Mycobacterium avium complex, Mycobacterium
      fortuitum group, Mycobacterium chelonae-Mycobacterium abscessus group,
      Mycobacterium xenopi and Mycobacterium gordonae. It provides a useful tool for
      the identification of MOTT when clinically indicated.

PMID- 17446281
TI  - Real-time RT-PCR for H5N1 avian influenza A virus detection.
AB  - The recent recurrence of highly pathogenic avian influenza virus A H5N1 was
      firstly reported in mid-December 2003 and continued through 2005. This study
      describes a sensitive and specific real-time RT-PCR method for the detection of
      influenza A subtype H5 and for monitoring virus loads. Using serial dilutions of
      influenza A H5N1 cultures, this assay reproducibly determined the lowest
      detection limit to be approximately 5 x 10(-2) 50 % egg infective doses
      (EID(50)). In contrast, the minimum detection limit was approximately 3 EID(50)
      in conventional RT-PCR with WHO primers and 10 EID(50) in antigen-capture ELISA.
      In tests of serial dilutions of in vitro-transcribed influenza A H5 gene RNA,
      there was linear amplification from 40 copies to 4 x 10(8) copies of target RNA
      per reaction and approximately six copies, and sometimes even as few as three
      copies, of target RNA tested positive in our assay. Thirty-five throat swabs from
      ill birds were tested: 33 samples tested positive using this assay. In
      comparison, 27, 13 and 19 samples tested positive using conventional RT-PCR,
      antigen-capture ELISA and virus isolation, respectively. To evaluate further the
      sensitivity of this real-time RT-PCR, a standard panel and 60 H5N1 isolates that
      contained different clades of influenza virus A/H5N1 were tested and all tested
      positive. To evaluate the specificity of the assay, 60 throat swabs from patients
      infected with influenza virus A H1 were tested; all were negative. Thirteen other
      viruses were also tested and all tested negative.

PMID- 17446282
TI  - The dominance of pandemic serovars of Vibrio parahaemolyticus in expatriates and
      sporadic cases of diarrhoea in Thailand, and a new emergent serovar (O3 : K46)
      with pandemic traits.
AB  - Vibrio parahaemolyticus is a major cause of gastroenteritis worldwide. A total of
      95 V. parahaemolyticus isolates belonging to 23 different serovars were
      identified in a case-control study of expatriates and Thai adults from 2001 to
      2002 in Thailand. Fifty-two per cent of isolates (49/95) were resistant to
      ampicillin and sulfisoxazole, but all isolates were susceptible to ciprofloxacin
      and trimethoprim-sulfamethoxazole, two antibiotics commonly used to treat
      traveller's diarrhoea. All isolates were positive for the species-specific toxR
      gene, and 91 and 5 were positive for the thermostable direct haemolysin (tdh)
      gene and the tdh-related (trh) gene, respectively. Sixty-five isolates were
      assigned to the pandemic group of V. parahaemolyticus by a group-specific PCR and
      the presence of the orf8 gene. The pandemic isolates belonged to three recognized
      serovars (O3 : K6, O1 : K25, O1 : KUT) and a new serovar, O3 : K46. This new
      serovar harboured pandemic traits. PFGE analysis revealed that all pandemic
      isolates including serovar O3 : K46 were closely related and clearly distinct
      from the non-pandemic isolates. In summary, three well-known serovars of pandemic
      V. parahaemolyticus isolates were identified as a major cause of diarrhoea in
      Thailand and a new V. parahaemolyticus isolate, serovar O3 : K46, with pandemic
      traits was detected.

PMID- 17446283
TI  - Rapid determination of hospital-acquired meticillin-resistant Staphylococcus
      aureus lineages.
AB  - Multilocus sequence typing (MLST) and multi-strain microarray analysis have shown
      that most human Staphylococcus aureus strains belong to ten dominant clonal
      complexes (CCs) or lineages, each with unique surface architecture. Meticillin
      resistant S. aureus (MRSA) strains currently belong to six of these lineages
      (CC1, CC5, CC8, CC22, CC30 and CC45), each of which has independently acquired
      mobile genetic elements (MGEs) carrying antibiotic resistance genes. MLST and
      microarrays are expensive and time consuming methods for routine determination of
      S. aureus lineage. A restriction-modification (RM) test has now been developed
      that is rapid, simple, inexpensive and accurately determines lineage of hospital
      acquired MRSA. The RM test is based on three PCRs for hsdS gene variants, as hsdS
      genes likely control the independent evolution of S. aureus lineages. The RM test
      correctly identified 102 MRSA isolates as belonging to one of the six
      lineages/CCs. Real-time MRSA typing can be used to identify and track changes in
      local MRSA outbreaks, and provide support for targeting infection control
      strategies. Simple and accurate typing methods will also support large scale
      epidemiological studies, and could lead to greater understanding of the carriage,
      spread and virulence of different MRSA lineages.

PMID- 17446285
TI  - Aloe vera leaf exudate induces a caspase-independent cell death in Leishmania
      donovani promastigotes.
AB  - Leishmaniasis constitutes a complex of diseases with clinical and epidemiological
      diversity and includes visceral leishmaniasis, a disease that is fatal when left
      untreated. In earlier studies, the authors reported that Aloe vera leaf exudate
      (AVL) is a potent antileishmanial agent effective in promastigotes of Leishmania
      braziliensis, Leishmania mexicana, Leishmania tropica, Leishmania major and
      Leishmania infantum and also in axenic amastigotes of Leishmania donovani. In the
      present study, it has been demonstrated that, in promastigotes of L. donovani
      (IC(50) = 110 microg ml(-1)), AVL mediates this leishmanicidal effect by
      triggering a programmed cell death. Incubation of promastigotes with AVL caused
      translocation of phosphatidylserine to the outer leaflet of the plasma membrane
      as measured by annexin V binding, which was accompanied by loss of mitochondrial
      membrane potential, release of cytochrome c into the cytosol and concomitant
      nuclear alterations that included chromatin condensation,
      deoxynucleotidyltransferase-mediated dUTP end labelling and DNA laddering. As
      this AVL-induced leishmanicidal effect could not be inhibited by protease
      inhibitors including Z-Val-Ala-dl-Asp (methoxy)-fluoromethylketone, a broad
      spectrum caspase inhibitor, non-involvement of caspases and major proteases was
      suggested. Additionally, AVL treatment caused no increase in cytosolic Ca(2+) or
      generation of reactive oxygen species, indicating that although promastigote
      death was induced by an apoptotic-like mechanism similar to metazoan apoptosis,
      the pathways of induction and/or execution differed at the molecular level.

PMID- 17446284
TI  - Sequence-based typing of genetic targets encoded outside of the O-antigen gene
      cluster is indicative of Shiga toxin-producing Escherichia coli serogroup
      lineages.
AB  - Serogroup classifications based upon the O-somatic antigen of Shiga toxin
      producing Escherichia coli (STEC) provide significant epidemiological information
      on clinical isolates. Each O-antigen determinant is encoded by a unique cluster
      of genes present between the gnd and galF chromosomal genes. Alternatively,
      serogroup-specific polymorphisms might be encoded in loci that are encoded
      outside of the O-antigen gene cluster. Segments of the core bacterial loci mdh,
      gnd, gcl, ppk, metA, ftsZ, relA and metG for 30 O26 STEC strains have previously
      been sequenced, and comparative analyses to O157 distinguished these two
      serogroups. To screen these loci for serogroup-specific traits within a broader
      range of clinically significant serogroups, DNA sequences were obtained for 19
      strains of 10 additional STEC serogroups. Unique alleles were observed at the gnd
      locus for each examined STEC serogroup, and this correlation persisted when
      comparative analyses were extended to 144 gnd sequences from 26 O-serogroups
      (comprising 42 O : H-serotypes). These included O157, O121, O103, O26, O5 : non
      motile (NM), O145 : NM, O113 : H21, O111 : NM and O117 : H7 STEC; and
      furthermore, non-toxin encoding O157, O26, O55, O6 and O117 strains encoded
      distinct gnd alleles compared to STEC strains of the same serogroup. DNA
      sequencing of a 643 bp region of gnd was, therefore, sufficient to minimally
      determine the O-antigen of STEC through molecular means, and the location of gnd
      next to the O-antigen gene cluster offered additional support for the co
      inheritance of these determinants. The gnd DNA sequence-based serogrouping method
      could improve the typing capabilities for STEC in clinical laboratories, and was
      used successfully to characterize O121 : H19, O26 : H11 and O177 : NM clinical
      isolates prior to serological confirmation during outbreak investigations.

PMID- 17446286
TI  - An antifungal protein from Escherichia coli.
AB  - A cytosolic protein was purified from Escherichia coli BL21 that demonstrated
      potent antifungal activity against pathogenic strains of Aspergillus fumigatus,
      Aspergillus flavus, Aspergillus niger and Candida albicans. The MIC of purified
      protein from E. coli BL21 (PPEBL21) against Aspergillus species and C. albicans
      was 1.95-3.98 and 15.62 microg ml(-1), respectively. In vitro toxicity tests
      demonstrated no cytotoxicity of PPEBL21 to human erythrocytes up to the tested
      concentrations of 1250 microg ml(-1). Amphotericin B was lethal to 100 % of human
      erythrocytes at a concentration of 37.5 microg ml(-1). The N-terminal amino acid
      sequence of PPEBL21 was found to be DLAEVASR, which showed 75 % sequence
      similarity with alcohol dehydrogenase of yeast. Mass fingerprinting by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry also
      substantiated these observations. The results suggested that E. coli BL21 might
      be an important bioresource of lead molecules for developing new peptide-based
      therapies for treating fungal infections.

PMID- 17446287
TI  - Enhancement of the in vitro activity of amphotericin B against the biofilms of
      non-albicans Candida spp. by rifampicin and doxycycline.
AB  - The in vitro activity of amphotericin B (AMB) alone and in combination with
      rifampicin (RIF) and doxycycline (DOX) was tested against the biofilms of 30
      clinical isolates of non-albicans Candida (NAC) species namely, Candida
      parapsilosis, Candida krusei and Candida glabrata. The killing activity of AMB at
      10 x MIC was significantly increased in combination with either antibiotic. With
      RIF, the killing activity increased by 20.6, 23.5 and 14 % against the biofilms
      of C. parapsilosis, C. krusei and C. glabrata, respectively; with DOX, the
      killing activity increased by 30.64, 35.28 and 31.13 %, respectively. Pre
      exposure of the isolates to the same combinations significantly reduced the
      number of colonized cells in the biofilms by 20, 25.14 and 13.07 % with RIF for
      C. parapsilosis, C. krusei and C. glabrata, respectively, and by 18.94, 24.52 and
      29.15 % with DOX, respectively. The data showed that combination of RIF or DOX
      with AMB enhanced the killing activity of the antifungal agent against biofilms
      of NAC species. Whether such an effect operates against biofilm-associated
      infections needs to be clarified by further in vivo studies.

PMID- 17446288
TI  - Association between fluconazole susceptibility and genetic relatedness among
      Candida tropicalis isolates in Taiwan.
AB  - Among the 162 Candida tropicalis isolates collected in the Taiwan Surveillance of
      Antimicrobial Resistance of Yeasts in 1999, 23 (14.2 %) had fluconazole MICs > or
      = 64 mg l(-1), and thus fulfilled the definition of resistance. Random amplified
      polymorphic DNA assay showed that all 23 fluconazole-resistance C. tropicalis
      isolates collected from different hospitals around Taiwan were closely related.
      Two distinct pulsotypes associated with fluconazole susceptibility were
      identified when these 23 resistant isolates, along with 13 susceptible ones, were
      analysed by PFGE.

PMID- 17446289
TI  - A novel serovar of Shigella dysenteriae from patients with diarrhoea in
      Bangladesh.
AB  - Every year, around 3 % of isolates from patients with diarrhoea at Dhaka
      Hospital, ICDDR,B, are identified as Shigella-like organisms (SLOs) based on
      their activity in biochemical tests. These isolates do not react with any of the
      current Shigella antisera including all existing and provisional serotypes. Among
      these SLOs, a unique cluster of seven isolates with an identical plasmid profile
      was found and these isolates were further characterized by phenotypic and
      genotypic techniques. All were nonlactose fermenters, with an identical
      biochemical pattern typical of Shigella dysenteriae. They were classified as
      invasive since they harboured the 140 MDa invasive plasmid, were able to bind
      Congo red, produced keratoconjunctivitis in the guinea pig eye, and were positive
      by PCR for the ipaH gene and Shigella enterotoxin 2 [ShET-2] gene. All isolates
      were resistant to ampicillin, tetracycline and sulfamethoxazole-trimethoprim but
      were susceptible to mecillinam, nalidixic acid, ceftriaxone and ciprofloxacin.
      Six of the isolates were identical in DNA pattern by PFGE with the seventh
      exhibiting a closely related pattern; both patterns were distinguishable from all
      other Shigella and Escherichia coli patterns. An antiserum prepared against one
      of the isolates reacted with all isolates and did not cross-react with other
      Shigella and E. coli serotype reference strains. It is therefore proposed that
      these isolates represent a new provisional serovar of S. dysenteriae, type strain
      KIVI 162.

PMID- 17446290
TI  - Effect of intensive handwashing in the prevention of diarrhoeal illness among
      patients with AIDS: a randomized controlled study.
AB  - Patients with AIDS frequently develop diarrhoeal illness. In this randomized,
      controlled study, 260 patients were screened for those who had not had diarrhoea
      in the preceding 3 months and who had received a stable highly active
      antiretroviral therapy regimen for at least 6 weeks prior to the study
      enrollment. A total of 148 patients met the inclusion criteria and were enrolled:
      75 patients were randomly assigned to an intensive handwashing intervention (i.e.
      handwashing after defecation, after cleaning infants who had defecated, before
      preparing food, before eating, and before and after sex) and 73 patients were
      randomly assigned to the control group. Patients in both groups were called
      weekly by telephone to determine compliance with handwashing and to determine the
      number of diarrhoeal episodes for the preceding week. Patients were observed for
      1 year. Patients assigned to the intensive handwashing intervention group washed
      their hands more frequently compared with the control group (seven vs four times
      a day, respectively; P <0.05) and developed fewer episodes of diarrhoeal illness
      (1.24+/-0.9 vs 2.92+/-0.6 new episodes of diarrhoea, respectively; P <0.001)
      during the 1 year observation. The most common pathogens identified in both
      groups in patients who developed diarrhoeal illness were Giardia lamblia,
      Cryptosporidium, Entamoeba histolytica and Shigella flexneri. These data suggest
      that intensive handwashing reduces diarrhoeal illness in patients with AIDS.

PMID- 17446292
TI  - Detection of antibodies to Pseudomonas aeruginosa in serum and oral fluid from
      patients with cystic fibrosis.
AB  - Cystic fibrosis (CF) patients who are chronically infected with Pseudomonas
      aeruginosa make serum antibodies to bacterial surface LPS as well as other
      pseudomonas antigens. This study investigated the feasibility of using oral fluid
      samples for the detection of pseudomonas antibodies in CF patients and compared
      these results with corresponding serum antibodies. Most strains of P. aeruginosa
      produce two forms of LPS molecule, termed A-band (described as a common antigen)
      and B-band (O-serotype-specific antigen), apparently bound to a common core
      oligosaccharide moiety. A-band LPS was demonstrated in 45 out of 49 clinical
      isolates of P. aeruginosa by SDS-PAGE and immunoblotting with a specific
      antibody. Oral fluids were collected from 17 adult CF patients, all of whom were
      sputum culture positive for P. aeruginosa (13 also provided serum samples), 11
      primary ciliary dyskinesia (PCD) patients and 37 healthy volunteers. Antibodies
      to A-band LPS were detected by immunoblotting in all of the CF patients' oral
      fluids but 10 of the volunteer samples gave weak reactions with immunoblotting.
      Six of the PCD patients gave a weak reaction with A-band antibodies and only one
      demonstrated antibodies to core LPS. In a quantitative ELISA, 15 of the 17 CF
      patients' oral fluids were shown to contain antibodies to A-band LPS, whilst none
      of the volunteer samples contained antibodies to A-band LPS. All serum samples
      from the CF patients were positive by both methods. Thus this is a sensitive
      procedure for the detection of antibodies to A-band LPS of P. aeruginosa in oral
      fluid and serum from patients with CF.

PMID- 17446291
TI  - Helicobacter pylori cag pathogenicity island genotype diversity within the
      gastric niche of a single host.
AB  - cag pathogenicity island (PAI) integrity was investigated in isolates from
      multiple biopsies recovered from 40 patients in an attempt to determine the co
      existence of a varying cagPAI-positive to cagPAI-negative ratio in a single host.
      Six biopsies were obtained from each patient during the same endoscopic session.
      cagPAI analysis included amplification of seven loci (cagA, cagE, cagG, cagM,
      cagT, HP0527 and HP0524) and the left end of cagII (LEC). Absence of the island
      was confirmed by empty-site PCR. lspA-glmM RFLP and random amplified polymorphic
      DNA PCR were used for strain delineation. The number of biopsies with
      Helicobacter pylori-positive culture ranged from three to six per patient and a
      total of 218 isolates were recovered. Mixed infection was only found in two
      patients. Nearly one-third of the 40 patients harboured isolates with an intact
      cagPAI in all niches, another third of the isolates were empty-site-positive in
      all niches, whilst the remaining third of the isolates had a disrupted cagPAI in
      all or at least one of the niches. Co-existence of variants of the same strain
      with different cagPAI genotypes was observed in one-quarter of patients. The
      variations in cagPAI genotype included co-existence of: diverse cagPAI deletions
      in different niches, variants with intact and with partially deleted islands,
      variants with empty-site-positive and with partially deleted cagPAIs, and
      variants with an intact cagPAI and with empty-site-positive. Half of the patients
      with different cagPAI genotypes harboured an intact cagPAI in at least one niche.
      Co-existence of diverse genotypes of putative virulence factors in a single host
      must be considered when drawing a correlation with clinical presentation.

PMID- 17446293
TI  - Enhancement of salivary IgA response to a DNA vaccine against Streptococcus
      mutans wall-associated protein A in mice by plasmid-based adjuvants.
AB  - A specific salivary IgA (sIgA) response was obtained in mice by intranasal
      immunization with a naked DNA vaccine consisting of the Streptococcus mutans wall
      associated protein A gene (wapA) inserted into the mammalian expression vector
      pcDNA3.1/V5/His-TOPO. In the present study, the vaccine, referred to as pcDNA
      wapA, was administered with or without the cationic lipid DMRIE-C. No mucosal
      response was observed in mice immunized with the vaccine alone, whereas a weak
      and temporal sIgA response was obtained when the vaccine was mixed with DMRIE-C.
      To investigate the use of pcDNA containing the interleukin 5 (IL-5) gene (pcDNA
      il-5) or the cholera toxin B gene (pcDNA-ctb) as genetic adjuvants, these
      constructs were used in co-immunization studies. The enhancement effect was
      transient with pcDNA-il-5, but longer lasting with pcDNA-ctb, thus supporting the
      use of the latter as a genetic adjuvant to DNA vaccine.

PMID- 17446294
TI  - The in vivo dynamics of Streptococcus spp., Actinomyces naeslundii, Fusobacterium
      nucleatum and Veillonella spp. in dental plaque biofilm as analysed by five
      colour multiplex fluorescence in situ hybridization.
AB  - The formation and composition of dental plaque biofilm in vivo are important
      factors which influence the development of gingivitis, caries and periodontitis.
      Studying dental plaque biofilm in in vitro models can cause an oversimplification
      of the real conditions in the oral cavity. In this study, bovine enamel slabs
      were fixed in an individual acrylic appliance in situ to quantify dental plaque
      formation and composition using multiplex fluorescence in situ hybridization
      (FISH) and confocal laser scanning microscopy. Each of the five oligonucleotide
      probes used for FISH was specific for either eubacteria or one of four frequently
      isolated bacterial constituents belonging to early and late colonizers of tooth
      surfaces. The thickness of formed biofilm increased from 14.9+/-5.0 microm after
      1 day to 49.3+/-11.6 microm after 7 days. Streptococcus spp. were predominant in
      1-day-old dental plaque and decreased significantly after 7 days (P=0.0061).
      Compared to the first day, Fusobacterium nucleatum decreased after 2 days and
      increased significantly after 7 days (P=0.0006). The decreases of Actinomyces
      naeslundii content on day 2 and day 7 were significant (P=0.0028). Changes in
      Veillonella spp. were not significant during the study period (P >0.05). The
      results showed that an in vivo observation period of 7 days was required to
      detect significant changes in Streptococcus spp. and F. nucleatum. The multiplex
      FISH used is suitable for analysing the dynamics of four important bacterial
      constituents in the oral biofilm in epidemiological studies.

PMID- 17446295
TI  - Candida glabrata colonizes but does not often disseminate from the mouse caecum.
AB  - Candida glabrata is the second or third most frequent cause of candidaemia. The
      gastrointestinal tract is considered to be a major portal of entry for systemic
      candidiasis, but relatively few studies have investigated the pathogenesis of C.
      glabrata. Experiments were designed to clarify the ability of C. glabrata to
      disseminate from the mouse intestinal tract. Following oral inoculation, C.
      glabrata readily colonized the caeca [approx. 10(7) cells (g caecum)(-1)] of
      antibiotic-treated mice, but extraintestinal dissemination was not detected.
      Superimposing several mouse models of trauma and/or immunosuppression known to
      induce dissemination of Candida albicans and other intestinal microbes did not
      cause C. glabrata to disseminate often, although one exception was mice given
      high doses of dexamethasone for 4 days. These data support the hypothesis that
      the antibiotic-treated mouse intestine may be an epidemiological reservoir for C.
      glabrata and that this yeast tends to disseminate under specific clinical
      conditions.

PMID- 17446296
TI  - Drug-resistant genital tuberculosis of the penis in a human immunodeficiency
      virus non-reactive individual.
AB  - The genitourinary tract is the most common site for extrapulmonary tuberculosis
      (TB). Penile TB is extremely rare comprising less than 1 % of all genital TB
      cases in males. It most commonly presents either as a superficial ulcer on the
      glans or around the corona. Diagnosis of penile TB is often difficult because it
      can mimic numerous other diseases. The association of TB with AIDS, and the
      increasing incidence of multiple drug resistance has further compounded the
      problem. The case described herein involves a patient with multidrug-resistant
      smear-positive penile TB that was undiagnosed initially due to the lack of
      clinical suspicion of TB, and once diagnosed failed to respond to first line
      antitubercular drugs because of multiple drug resistance.

PMID- 17446297
TI  - A case of severe pancreatitis complicated by Raoultella planticola infection.
AB  - A 45-year-old-male presented with severe pancreatitis. Two bacterial isolates
      obtained from peritoneal fluid and abdominal purulent secretion were identified
      to the species level by 15 biochemical tests and four supplementary tests as
      Raoultella planticola. Identification was confirmed by rpoB gene sequencing. R.
      planticola is difficult to identify in the clinical laboratory, and the clinical
      significance of this isolation remains uncharacterized. This is the first report
      of pancreatitis with a primary infection by R. planticola.

PMID- 17446298
TI  - Rhizopus microsporus var. rhizopodiformis sinus-orbital zygomycosis in an
      immunosuppressed patient: successful treatment with posaconazole after a
      complicated clinical course.
AB  - A case of sinus-orbital Rhizopus microsporus var. rhizopodiformis infection in a
      patient with graft versus host disease following allogeneic blood stem cell
      transplantation is reported. Commercially available pea straw compost used for
      gardening was suspected to be the source of the infection. After an initial
      relapse, treatment with surgical debridement, liposomal amphotericin B and
      posaconazole was successful.

PMID- 17446299
TI  - Bacteria-associated haemophagocytic syndrome and septic pulmonary embolism caused
      by Burkholderia cepacia complex in a woman with chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized
      by recurrent infections with certain types of bacteria and fungi. Presented
      herein is the case of a 29 year old woman with CGD who suffered from bacteria
      associated haemophagocytic syndrome and a septic pulmonary embolism following a
      uterine infection and sepsis, caused by Burkholderia cepacia complex.

PMID- 17446300
TI  - Competitive antagonism between the nicotinic allosteric potentiating ligand
      galantamine and kynurenic acid at alpha7* nicotinic receptors.
AB  - Galantamine, a drug used to treat Alzheimer's disease, is a nicotinic allosteric
      potentiating ligand, and kynurenic acid (KYNA), a neuroactive metabolite of the
      kynurenine pathway, is an endogenous noncompetitive inhibitor of alpha7*
      nicotinic receptors (nAChRs) [the asterisk next to the nAChR subunit is intended
      to indicate that the exact subunit composition of the receptor is not known
      (Pharmacol Rev 51:397-401, 1999)]. Here, possible interactions between KYNA and
      galantamine at alpha7* nAChRs were examined in vitro and in vivo. In the presence
      of tetrodotoxin (TTX), approximately 85% of cultured hippocampal neurons
      responded to choline (0.3-30 mM) with alpha7* nAChR-subserved whole-cell (type
      IA) currents. In the absence of TTX and in the presence of glutamate receptor
      antagonists, choline triggered inhibitory postsynaptic currents (IPSCs) by
      activating alpha7* nAChRs on GABAergic neurons synapsing onto the neurons under
      study. Galantamine (1-10 microM) potentiated, whereas KYNA (10 nM-1 mM)
      inhibited, choline-triggered responses. Galantamine (1 microM), applied before
      KYNA, shifted to the right the concentration-response relationship for KYNA to
      inhibit type IA currents, increasing the IC(50) of KYNA from 13.9 +/- 8.3 to 271
      +/- 131 microM. Galantamine, applied before or after KYNA, antagonized inhibition
      of choline-triggered IPSCs by KYNA. Local infusion of KYNA (100 nM) in the rat
      striatum reduced extracellular dopamine levels in vivo. This effect resulted from
      alpha7* nAChR inhibition and was blocked by coapplied galantamine (1-5 microM).
      It is concluded that galantamine competitively antagonizes the actions of KYNA on
      alpha7* nAChRs. Reducing alpha7* nAChR inhibition by endogenous KYNA may be an
      important determinant of the effectiveness of galantamine in neurological and
      psychiatric disorders associated with decreased alpha7* nAChR activity in the
      brain.

PMID- 17446301
TI  - Wash-resistantly bound xanomeline inhibits acetylcholine release by persistent
      activation of presynaptic M(2) and M(4) muscarinic receptors in rat brain.
AB  - We studied the effects of 3-[3-hexyloxy-1,2,5-thiadiazo-4-yl]-1,2,5,6-tetrahydro
      1-methylpyridine (xanomeline) wash-resistant binding on presynaptic muscarinic
      regulation of electrically evoked [(3)H]acetylcholine (ACh) release from rat
      brain slices. In both cortical and striatal tissues that possess M(2) and M(4)
      autoreceptors, respectively, immediate application of 10 microM xanomeline had no
      effect on evoked [(3)H]ACh release or its inhibition by 10 microM carbachol. In
      contrast, preincubation with 1, 10, or 100 microM xanomeline for 15 min decreased
      evoked release of ACh measured after 53 min of washing in xanomeline-free medium
      in a concentration-dependent manner. The maximal inhibitory effect equaled the
      immediate effect of the muscarinic full agonist carbachol, and it was completely
      (at 1 and 10 microM xanomeline) or partially (at 100 microM xanomeline) blocked
      by 1 microM N-methylscopolamine. Neither presence of N-methylscopolamine during
      100 microM xanomeline treatment nor previous irreversible inactivation of the
      classical receptor binding site using propylbenzylcholine mustard in cortical
      slices prevented the inhibitory effect of wash-resistantly bound xanomeline.
      Treatment of cortical slices with xanomeline slightly decreased the number of
      muscarinic binding sites, and it markedly decreased affinity for N
      methylscopolamine. When applied as in acetylcholine release experiments,
      xanomeline did not impair presynaptic alpha(2)-adrenoceptor-mediated regulation
      of noradrenaline release. The functional studies in brain tissue reported in this
      work demonstrate that xanomeline can function as a wash-resistant agonist of
      native presynaptic muscarinic M(2) and M(4) receptors with both competitive and
      allosteric components of action.

PMID- 17446302
TI  - Nicotine dependence and reward differ between adolescent and adult male mice.
AB  - The present study defined age differences in several aspects of nicotine
      dependence using male mice of two age groups [postnatal day (PND) 28 and PND 70].
      Adolescent and adult mice displayed differences in acute sensitivity to nicotine,
      rewarding and withdrawal effects, development of tolerance to nicotine, and
      nicotinic receptor function. In the condition place preference model, adolescent
      mice displayed a higher sensitivity to nicotine than adults. In addition, in
      spontaneous and mecamylamine-precipitated withdrawal models, adolescent mice
      displayed fewer withdrawal signs than adults. In response to acute nicotine, it
      was found that adolescent mice displayed greater nicotine-induced antinociception
      compared with adult counterparts in the tail-flick test. Furthermore, differences
      in tolerance to nicotine were also noted in that adolescents developed a
      significantly higher degree of tolerance to nicotine in the hot-plate test
      compared with adults. Finally, using rubidium efflux assays, it was found that
      adolescent nicotinic receptors in different brain areas displayed significantly
      increased functionality compared with adult receptors. These data indicate that
      the underlying receptor mechanisms of nicotine dependence differ for adults and
      adolescents, suggesting that the effectiveness of smoking cessation therapies
      will differ for various age groups.

PMID- 17446303
TI  - Chronic nicotine differentially regulates alpha6- and beta3-containing nicotinic
      cholinergic receptors in rat brain.
AB  - We investigated the effects of chronic nicotine on alpha6- and beta3-containing
      nicotinic acetylcholine receptors (nAChRs) in two rat brain regions using three
      methodological approaches: radioligand binding, immunoprecipitation, and nicotine
      stimulated synaptosomal release of dopamine. Nicotine was administered by osmotic
      minipumps for 2 weeks. Quantitative autoradiography with [(125)I]alpha-conotoxin
      MII to selectively label alpha6(*) nAChRs showed a 28% decrease in binding in the
      striatum but no change in the superior colliculus. Immunoprecipitation of nAChRs
      labeled by [(3)H]epibatidine in these two regions showed that chronic nicotine
      increased alpha4- and beta2-containing nAChRs by 39 to 67%. In contrast, chronic
      nicotine caused a 39% decrease in alpha6-containing nAChRs in striatum but no
      change in superior colliculus. No changes in beta3-containing nAChRs were seen in
      either region after chronic nicotine. The decreased expression of alpha6
      containing nAChRs persisted for at least 3 days, recovering to baseline by 7 days
      after removal of the pumps. There was a small but significant decrease in total
      nicotine-stimulated dopamine release in striatal synaptosomes after nicotine
      exposure. However, the component of dopamine release that was resistant to alpha
      conotoxin MII blockade was unaffected, whereas dopamine release that was
      sensitive to blockade by alpha-conotoxin MII was decreased by 56%. These findings
      indicate that the alpha6(*) nAChR is regulated differently from other nAChR
      subtypes, and they suggest that the inclusion of a beta3 subunit with alpha6 may
      serve to inhibit nicotine-induced down-regulation of these receptors.

PMID- 17446304
TI  - Patterns of GI disease in adulthood associated with mutations in the CFTR gene.

PMID- 17446305
TI  - Giving APCmin tumours a SPARC.

PMID- 17446306
TI  - Effect of a second-generation alpha2delta ligand (pregabalin) on visceral
      sensation in hypersensitive patients with irritable bowel syndrome.
AB  - BACKGROUND: Visceral hypersensitivity is an important pathophysiological factor
      in irritable bowel syndrome (IBS). Pre-clinical studies suggest that the
      alpha(2)delta ligand pregabalin reduces both visceral allodynia and hyperalgesia,
      but is inactive on basal sensitivity. AIM: To assess the effect of pregabalin on
      the perception of rectal distension in hypersensitive IBS patients. METHODS:
      Twenty-six patients with Rome-II-defined IBS (aged 18-46 years, 7 male) were
      included in a randomized, double-blind, placebo-controlled, parallel-group study
      in which they received either 3 weeks oral pregabalin (titrated: 50 mg tid days 1
      3, 100 mg tid days 4-7, 150 mg tid days 8-11; fixed 200 mg tid days 12-21 +/-4)
      or placebo control. Rectal sensitivity was assessed using a barostat technique,
      in which sensory thresholds were determined using the ascending method of limits,
      followed by tracking both before and after treatment. Only patients with a pain
      threshold of <or=28 mmHg were included in the study. RESULTS: Pregabalin
      significantly increased the sensory thresholds from baseline for first sensation
      (p = 0.045), desire to defecate (p = 0.008) and pain (p = 0.048) compared with
      placebo control. In addition, pregabalin significantly increased rectal
      compliance (p<0.0001), although this appeared to be unrelated to the changes in
      sensitivity. Despite the occurrence of mild dizziness and somnolence, pregabalin
      was generally well tolerated. CONCLUSIONS: Pregabalin increased distension
      sensory thresholds to normal levels in IBS patients with rectal hypersensitivity.
      A concomitant increase in rectal compliance appeared to be unrelated to the
      reduction in sensitivity. These data suggest that alpha(2)delta ligands are
      worthy of further investigation in the treatment of visceral pain disorders,
      including IBS.

PMID- 17446307
TI  - Suppressors of zyg-1 define regulators of centrosome duplication and nuclear
      association in Caenorhabditis elegans.
AB  - In Caenorhabditis elegans, the kinase ZYG-1 is required for centrosome
      duplication. To identify factors that interact with ZYG-1, we used a classical
      genetic approach and identified 21 szy (suppressor of zyg-1) genes that when
      mutated restore partial viability to a zyg-1 mutant. None of the suppressors
      render animals completely independent of zyg-1 activity and analysis of a subset
      of the suppressors indicates that all restore the normal process of centrosome
      duplication to zyg-1 mutants. Thirteen of these suppressor mutations confer
      phenotypes of their own and cytological examination reveals that these genes
      function in a variety of cellular processes including cell cycle timing,
      microtubule organization, cytokinesis, chromosome segregation, and centrosome
      morphology. Interestingly, several of the szy genes play a role in attaching the
      centrosome to the nuclear envelope. We have found that one such szy gene is sun
      1, a gene encoding a nuclear envelope component. We further show that the role of
      SUN-1 in centrosome duplication is distinct from its role in attachment. Our
      approach has thus identified numerous candidate regulators of centrosome
      duplication and uncovered an unanticipated regulatory mechanism involving factors
      that tether the centrosome to the nucleus.

PMID- 17446308
TI  - Lipopolysaccharide disrupts tight junctions in cholangiocyte monolayers by a c
      Src-, TLR4-, and LBP-dependent mechanism.
AB  - Bile duct epithelium forms a barrier to the backflow of bile into the liver
      parenchyma. However, the structure and regulation of the tight junctions in bile
      duct epithelium is not well understood. In the present study, we evaluated the
      effect of lipopolysaccharide on tight junction integrity and barrier function in
      normal rat cholangiocyte monolayers. Lipopolysaccharide disrupts barrier function
      and increases paracellular permeability in a time- and dose-dependent manner.
      Lipopolysaccharide induced a redistribution of tight junction proteins, occludin,
      claudin-1, claudin-4, and zonula occludens (ZO)-1 from the intercellular
      junctions and reduced the level of ZO-1. Tyrosine kinase inhibitors (genistein
      and PP2) prevented lipopolysaccharide-induced increase in permeability and
      subcellular redistribution of ZO-1. Reduced expression of c-Src, TLR4, or LBP by
      specific small interfering RNA attenuated lipopolysaccharide-induced permeability
      and redistribution of ZO-1. ML-7, a myosin light chain kinase inhibitor,
      attenuated LPS-induced permeability. Lipopolysaccharide treatment rapidly
      increased the phosphorylation of occludin and ZO-1 on tyrosine residues, which
      was prevented by genistein and PP2. Occludin and ZO-1 were found to be highly
      phosphorylated on threonine residues in intact cell monolayers. Threonine
      phosphorylation of occludin was rapidly reduced by lipopolysaccharide
      administration. Lipopolysaccharide-induced dephosphorylation of occludin on Thr
      residues was prevented by genistein and PP2. In conclusion, lipopolysaccharide
      disrupts the tight junction of a bile duct epithelial monolayer by a c-Src-, TLR4
      , LBP-, and myosin light chain kinase-dependent mechanism.

PMID- 17446309
TI  - S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury.
AB  - Pyrazole treatment to induce cytochrome P-450 2E1 (CYP2E1) was recently shown to
      cause liver injury in ob/ob mice but not in lean mice. The present study
      investigated the effects of S-adenosyl-l-methionine (SAM) on the CYP2E1-dependent
      liver injury in ob/ob mice. Pyrazole treatment of ob/ob mice for 2 days caused
      necrosis, steatosis, and elevated serum transaminase and triglyceride levels
      compared with saline ob/ob mice. Administration of SAM (50 mg/kg body wt ip every
      12 h for 3 days) prevented the observed pathological changes as well as the
      increase of apoptotic hepatocytes, caspase 3 activity, and serum TNF-alpha
      levels. SAM administration inhibited CYP2E1 activity but not CYP2E1 content. The
      pyrazole treatment increased lipid peroxidation, 4-hydroxynonenal and 3
      nitrotyrosine protein adducts, and protein carbonyls. These increases in
      oxidative and nitrosative stress were prevented by SAM. Treatment of ob/ob mice
      with pyrazole lowered the endogenous SAM levels, and these were elevated after
      SAM administration. Mitochondrial GSH levels were very low after pyrazole
      treatment of the ob/ob mice; this was associated with elevated levels of
      malondialdehyde and 4-hydroxynonenal and 3-nitrotyrosine protein adducts in the
      mitochondria. All these changes were prevented with SAM administration. SAM
      protected against pyrazole-induced increase in serum transaminases, necrosis,
      triglyceride levels, caspase-3 activity, and lipid peroxidation even when
      administered 1 day after pyrazole treatment. In the absence of pyrazole, SAM
      lowered the slightly elevated serum transaminases, triglyceride levels, caspase-3
      activity, and lipid peroxidation in obese mice. In conclusion, SAM protects
      against and can also reverse or correct CYP2E1-induced liver damage in ob/ob
      mice.

PMID- 17446323
TI  - StaphPlex system for rapid and simultaneous identification of antibiotic
      resistance determinants and Panton-Valentine leukocidin detection of
      staphylococci from positive blood cultures.
AB  - Phenotypic methods take several days for identification and antimicrobial
      susceptibility testing of staphylococcal isolates after gram-positive cocci in
      clusters (GPCC) are observed in positive blood cultures. We developed and
      validated a StaphPlex system that amplifies and detects 18 gene targets
      simultaneously in 1 reaction for species-level identification of staphylococci,
      detection of genes encoding Panton-Valentine leukocidin (PVL), and antimicrobial
      resistance determinants of staphylococci. The StaphPlex system was compared to
      phenotypic methods for organism identification and antimicrobial resistance
      detection for positive blood culture specimens in which GPCC were observed. Among
      a total of 360 GPCC specimens, 273 (75.8%), 37 (10.3%), 37 (10.3%), 1 (0.3%), 3
      (0.8%), and 9 (2.5%) were identified by StaphPlex as coagulase-negative
      Staphylococcus (CoNS), methicillin-resistant Staphylococcus aureus (MRSA),
      methicillin-susceptible S. aureus (MSSA), or mixed infections of CoNS and MRSA,
      CoNS and MSSA, or nonstaphylococci, respectively, with an overall accuracy of
      91.7%. The 277 CoNS-containing specimens were further identified to the species
      level as containing 203 (73.3%) Staphylococcus epidermidis isolates, 10 (3.6%)
      Staphylococcus haemolyticus isolates, 27 (9.7%) Staphylococcus hominis isolates,
      1 (0.4%) Staphylococcus lugdunensis isolate, and 36 (13.0%) other CoNS isolates,
      with an overall accuracy of 80.1% compared to an API STAPH test and CDC reference
      identification. Numerous very major errors were noticed when detection of aacA,
      ermA, ermC, tetM, and tetK was used to predict in vitro antimicrobial resistance,
      but relatively few major errors were observed when the absence of these genes was
      used to predict susceptibility. The StaphPlex system demonstrated 100%
      sensitivity and specificity, ranging from 95.5% to 100.0% when used for
      staphylococcal cassette chromosome mec typing and PVL detection. StaphPlex
      provides simultaneous staphylococcal identification and detection of PVL and
      antimicrobial resistance determinants within 5 h, significantly shortening the
      time needed for phenotypic identification and antimicrobial susceptibility
      testing.

PMID- 17446324
TI  - Isolation of Nocardia asiatica from cutaneous ulcers of a human immunodeficiency
      virus-infected patient in Italy.
AB  - A strain of Nocardia was isolated from cutaneous ulcers of a human
      immunodeficiency virus-infected patient in Italy. Comparative 16S rRNA gene
      sequence analysis revealed that the isolate represented a strain of Nocardia
      asiatica. Antimicrobial susceptibility testing was essential to guide the
      clinicians to successfully treat this infection.

PMID- 17446325
TI  - Evaluation of different clinical sample types in diagnosis of human enterovirus
      71-associated hand-foot-and-mouth disease.
AB  - Human enterovirus 71 and coxsackievirus A16 are important causes of hand-foot-and
      mouth disease (HFMD). Like other enteroviruses, they can be isolated from a range
      of sterile and nonsterile sites, but which clinical sample, or combination of
      samples, is the most useful for laboratory diagnosis of HFMD is not clear. We
      attempted virus culture for 2,916 samples from 628 of 725 children with HFMD
      studied over a 3 1/2-year period, which included two large outbreaks. Overall,
      throat swabs were the single most useful specimen, being positive for any
      enterovirus for 288 (49%) of 592 patients with a full set of samples. Vesicle
      swabs were positive for 169 (48%) of 333 patients with vesicles, the yield being
      greater if two or more vesicles were swabbed. The combination of throat plus
      vesicle swabs enabled the identification of virus for 224 (67%) of the 333
      patients with vesicles; for this patient group, just 27 (8%) extra patients were
      diagnosed when rectal and ulcer swabs were added. Of 259 patients without
      vesicles, use of the combination of throat plus rectal swab identified virus for
      138 (53%). For 60 patients, virus was isolated from both vesicle and rectal
      swabs, but for 12 (20%) of these, the isolates differed. Such discordance
      occurred for just 11 (10%) of 112 patients with virus isolated from vesicle and
      throat swabs. During large HFMD outbreaks, we suggest collecting swabs from the
      throat plus one other site: vesicles, if these are present (at least two should
      be swabbed), or the rectum if there are no vesicles. Vesicle swabs give a high
      diagnostic yield, with the added advantage of being from a sterile site.

PMID- 17446326
TI  - Subtyping method for Escherichia coli shiga toxin (verocytotoxin) 2 variants and
      correlations to clinical manifestations.
AB  - Shiga toxin 2 (Stx2) from Shiga toxin-producing Escherichia coli (STEC) was
      subtyped by a method involving partial sequencing of the stxAB2 operon. Of 255
      strains from the Danish STEC cohort, all 20 cases of hemolytic-uremic syndrome
      were associated with subtype Stx2 (11 cases), subtype Stx2c (1 case), or the two
      combined (8 cases).

PMID- 17446327
TI  - Tropheryma whipplei infective endocarditis as the only manifestation of Whipple's
      disease.
AB  - Here we describe a case of infective endocarditis caused by Tropheryma whipplei
      in a patient with no other symptoms of Whipple's disease. The case was diagnosed
      using broad-range PCR and confirmed by specific PCRs. We review the cases of
      infective endocarditis presenting as the only manifestation of Whipple's disease
      reported in the literature.

PMID- 17446328
TI  - Distinct pathotypes of O113 Escherichia coli strains isolated from humans and
      animals in Brazil.
AB  - Two distinct diarrheagenic Escherichia coli pathotypes, enteroaggregative E. coli
      (EAEC) and Shiga toxin-producing E. coli, were observed in association with O113
      strains isolated from human and nonhuman sources in Brazil, respectively. The
      O113 strains from human diarrhea belonged to a diversity of serotypes, and nine
      (53%) of them harbored virulence traits of typical EAEC.

PMID- 17446329
TI  - The -256T>C polymorphism in the apolipoprotein A-II gene promoter is associated
      with body mass index and food intake in the genetics of lipid lowering drugs and
      diet network study.
AB  - BACKGROUND: Apolipoprotein A-II (APOA2) plays an ambiguous role in lipid
      metabolism, obesity, and atherosclerosis. METHODS: We studied the association
      between a functional APOA2 promoter polymorphism (-265T>C) and plasma lipids
      (fasting and postprandial), anthropometric variables, and food intake in 514 men
      and 564 women who participated in the Genetics of Lipid Lowering Drugs and Diet
      Network (GOLDN) study. We obtained fasting and postprandial (after consuming a
      high-fat meal) measures. We measured lipoprotein particle concentrations by
      proton nuclear magnetic resonance spectroscopy and estimated dietary intake by
      use of a validated questionnaire. RESULTS: We observed recessive effects for this
      polymorphism that were homogeneous by sex. Individuals homozygous for the -265C
      allele had statistically higher body mass index (BMI) than did carriers of the T
      allele. Consistently, after multivariate adjustment, the odds ratio for obesity
      in CC individuals compared with T allele carriers was 1.70 (95% CI 1.02-2.80, P =
      0.039). Interestingly, total energy intake in CC individuals was statistically
      higher [mean (SE) 9371 (497) vs 8456 (413) kJ/d, P = 0.005] than in T allele
      carriers. Likewise, total fat and protein intakes (expressed in grams per day)
      were statistically higher in CC individuals (P = 0.002 and P = 0.005,
      respectively). After adjustment for energy, percentage of carbohydrate intake was
      statistically lower in CC individuals. These associations remained statistically
      significant even after adjustment for BMI. We found no associations with fasting
      lipids and only some associations with HDL subfraction distribution in the
      postprandial state. CONCLUSIONS: The -265T>C polymorphism is consistently
      associated with food consumption and obesity, suggesting a new role for APOA2 in
      regulating dietary intake.

PMID- 17446330
TI  - Utilization and diagnostic yield of neurogenetic testing at a tertiary care
      facility.
AB  - BACKGROUND: Institutions face increasing charges related to molecular genetic
      testing for neurological diseases. The literature contains little information on
      the utilization and performance of these tests. METHODS: A retrospective
      utilization review was performed to determine the diagnostic yield of
      neurogenetic tests ordered during calendar year 2005 at a large academic medical
      center in the western United States. RESULTS: Overall, a relevant mutation was
      identified in 30.2% of the 162 patients tested and in 21.5% of the 121 probands,
      defined as patients for whom no mutation has been previously identified in a
      family member. Patients with muscle weakness (n = 65) had a mutation detected in
      26.2% of all patients and 23.5% of probands (n = 51), with an estimated testing
      cost per positive result of $3190. Patients tested for neuropathy (n = 36) had a
      mutation detected in 27.8% of patients and 22.6% of probands (n = 31), with an
      estimated cost per positive result of $5955. Patients with chorea (n = 25) had a
      positive result obtained in 68% of patients and 71.4% of probands (n = 7); the
      estimated cost per positive test was $440. Other diagnostic categories evaluated
      include ataxias (n = 18; yield, 11.1%; $7620 per positive), familial stroke or
      dementia syndromes (n = 8; yield, 12.5%; $6760 per positive), and multisystem
      mitochondrial disorders (n = 10; yield, 20%; $6485 per positive). CONCLUSIONS:
      Expert clinicians at a tertiary care center who ordered neurogenetic tests
      obtained a positive result in 21.5% of patients without previously identified
      familial mutations. These results can be used for comparison and to help
      establish utilization guidelines for neurogenetic testing.

PMID- 17446331
TI  - Quantitative mitochondrial DNA mutation analysis by denaturing HPLC.
AB  - BACKGROUND: In recent years, denaturing HPLC (DHPLC) has been widely used to
      screen the whole mitochondrial genome or specific regions of the genome for DNA
      mutations. The quantification and mathematical modeling of DHPLC results is,
      however, underexplored. METHODS: We generated site-directed mutants containing
      some common mutations in the mitochondrial DNA (mtDNA) tRNA(leu) region with
      different mutation loads and used PCR to amplify the gene segment of interest in
      these mutants. We then performed restriction digestion followed by slow
      reannealing to induce heteroduplex formation and analyzed the samples by use of
      DHPLC. RESULTS: We observed a quadratic relationship between the heteroduplex
      peak areas and mutant loads, consistent with the kinetics of heteroduplex
      formation reported by others. This was modeled mathematically and used to
      quantify mtDNA mutation load. The method was able to detect a mutation present in
      a concentration as low as 1% and gave reproducible measurements of the mutations
      in the range of 2.5%-97.5%. CONCLUSION: The quantitative DHPLC assay is well
      suited for simultaneous detection and quantification of DNA mutations.

PMID- 17446332
TI  - Ultrasensitive densitometry detection of cytokines with nanoparticle-modified
      aptamers.
AB  - BACKGROUND: Aptamers mimic properties of antibodies and sometimes turn out to be
      even better than antibodies as reagents for assays. We describe the establishment
      of an ultrasensitive densitometry method for cytokine detection by nanoparticle
      (NP)-modified aptamers. METHODS: The assay simultaneously uses a gold NP-modified
      aptamer and a biotin-modified aptamer to bind to the target protein, forming a
      sandwich complex. The absorbance signal generated by the aptamer-protein complex
      is amplified and detected with a microplate reader. RESULTS: The assay for
      platelet-derived growth factor B-chain homodimer (PDGF-BB) was linear from 1
      fmol/L to 100 pmol/L (R(2) = 0.9869). The analytical detection limit was 83
      amol/L. The intraassay and interassay imprecision (CVs) was < or =7.5%. Serum
      concentrations of PDGF-BB determined with the gold NP-modified aptamer assay and
      with ELISA were not significantly different. CONCLUSIONS: The gold NP-modified
      aptamer assay provides a fast, convenient method for cytokine detection and
      improves the detection range and the detection limit compared with ELISA.

PMID- 17446333
TI  - N-terminal pro-B-type natriuretic peptide predicts total and cardiovascular
      mortality in individuals with or without stable coronary artery disease: the
      Ludwigshafen Risk and Cardiovascular Health Study.
AB  - BACKGROUND: Measurement of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP)
      measurement can be used to predict mortality in patients with acute coronary
      syndromes. Information on the value of NT-pro-BNP in clinically stable persons
      scheduled for angiography is limited. METHODS: We used Cox proportional hazards
      regression to examine the effect of NT-pro-BNP on total and cardiovascular
      mortality in 1135 with and 506 individuals without stable coronary artery disease
      (CAD). RESULTS: NT-pro-BNP was associated with New York Heart Association
      functional class, left ventricular (LV) systolic function, and LV end-diastolic
      pressure. NT-pro-BNP was positively related to age, female sex, hypertension, and
      former and current smoking and negatively related to body mass index and
      glomerular filtration rate. During a median follow-up of 5.45 years, NT-pro-BNP
      concentrations of 100-399, 400-1999, or > or =2000 ng/L resulted in unadjusted
      hazard ratios (95% CI) for all-cause death of 3.2 (1.8-5.6), 6.63 (3.8-11.6), and
      16.5 (9.2-29.8), respectively, compared with concentrations <100 ng/L. Hazard
      ratios (CI) for death from cardiovascular causes were 3.8 (1.8-8.2), 9. 3 (4.4
      19.5), and 22.2 (10.2-48.4). NT-pro-BNP remained predictive of total and
      cardiovascular mortality after accounting for age, sex, diabetes mellitus, body
      mass index, smoking, hypertension, dyslipidemia, glomerular filtration rate,
      presence or absence of CAD on angiography, cardiovascular medication,
      revascularization at baseline, clinical signs of heart failure, LV systolic
      function, and C-reactive protein. CONCLUSIONS: NT-pro-BNP is predictive of all
      cause and cardiovascular mortality in individuals with or without stable
      angiographic CAD independently of other cardiovascular risk factors, coronary
      atherosclerosis, and cardiac function.

PMID- 17446334
TI  - Bronchial responsiveness in atopic adults increases with exposure to cat
      allergen.
AB  - RATIONALE: The association of asthma with sensitization and allergen exposure is
      known to be complex. There have been few studies of bronchial responsiveness in
      relation to both risk factors in adults. OBJECTIVES: To determine the relation of
      bronchial responsiveness to allergen exposure and IgE sensitization in a
      community study taking into account the major determinants of bronchial
      responsiveness in adulthood. METHODS: Cross-sectional data were drawn from 1,884
      participants in 20 centers in the European Community Respiratory Health Survey
      follow-up, which included measurement of house dust mite and cat allergen in
      mattress dust samples, and IgE sensitization to four allergens. Bronchial
      responsiveness to methacholine was expressed as a continuous variable, and
      analyzed by multiple regression. MEASUREMENTS AND MAIN RESULTS: The trend toward
      greater bronchial responsiveness with increasing exposure to cat allergen was
      greater in those sensitized to any of the four allergens than those not
      sensitized (p = 0.001); there was no significant interaction between cat
      sensitization and Fel d 1 exposure. No trend was found with house dust mite
      allergen exposure. The difference in bronchial responsiveness between those
      exposed to the highest levels compared with the lowest was approximately -2.02
      doubling doses of PD20 (95% confidence interval, -3.06 to -0.97), and nearly as
      great in those exposed to more moderate levels. CONCLUSIONS: Cat allergen
      exposure at moderate levels may be harmful to all atopic adults. The clinical
      implication is that it is insufficient to test patients with asthma for cat
      sensitization; all atopic individuals may benefit from reduced cat exposure.

PMID- 17446335
TI  - The SERPINE2 gene is associated with chronic obstructive pulmonary disease in two
      large populations.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is a complex disease
      influenced by multiple genes and environmental factors. A region on chromosome 2q
      has been shown to be linked to COPD. A positional candidate gene from the
      chromosome 2q region SERPINE2 (Serpin peptidase inhibitor, clade E [nexin,
      plasminogen activator inhibitor type 1], member 2), was previously evaluated as a
      susceptibility gene for COPD in two association studies, but the results were
      contradictory. OBJECTIVES: To identify the relationship between SERPINE2
      polymorphisms and COPD-related phenotypes using family-based and case-control
      association studies. METHODS: In the present study, we genotyped 25 single
      nucleotide polymorphisms (SNPs) from SERPINE2 and analyzed qualitative and
      quantitative COPD phenotypes in 635 pedigrees with 1,910 individuals and an
      independent case-control population that included 973 COPD cases and 956 control
      subjects. The family data were analyzed using family-based association tests. The
      case-control data were analyzed using logistic regression and linear models.
      MEASUREMENTS AND MAIN RESULTS: Six SNPs demonstrated significant associations
      with COPD phenotypes in the family-based association analysis
      (0.0016<or=p<or=0.042). Five of these SNPs demonstrated replicated associations
      in the case-control analysis (0.021<or=p<or=0.031). In addition, the results of
      haplotype analyses supported the results from single SNP analyses. CONCLUSIONS:
      These data provide further support for SERPINE2 as a COPD susceptibility gene.

PMID- 17446336
TI  - Galectin-9 inhibits CD44-hyaluronan interaction and suppresses a murine model of
      allergic asthma.
AB  - RATIONALE: Galectin-9 (Gal-9) belongs to the galectin family, which exhibits
      affinity for beta-galactosides. Gal-9 has a variety of biological activities;
      however, its role in allergic inflammation is unknown. OBJECTIVES: We evaluated
      the effect of a stable form of the human protein on allergic airway inflammation
      in a mite allergen-induced asthma model. METHODS: Human stable Gal-9 was given by
      intravenous injection to mice during antigen challenge. The effect of Gal-9 on
      airway inflammation and airway hyperresponsiveness (AHR) was then evaluated.
      MEASUREMENTS AND MAIN RESULTS: Gal-9 reduced AHR as well as Th2-associated airway
      inflammation. Furthermore, administration of Gal-9 as well as anti-CD44
      monoclonal antibody inhibited the infiltration of peripheral blood Th2 cells into
      the airway. Interestingly, Gal-9 directly bound the CD44 adhesion molecule and
      inhibited interactions with hyaluronan (HA). Consistent with the concept that
      CD44-HA interactions mediate the migration of T cells into the lung, Gal-9
      blocked CD44-dependent adhesion of BW5147 mouse T cells to HA. CONCLUSIONS: We
      conclude that Gal-9 inhibits allergic inflammation of the airway and AHR by
      modulating CD44-dependent leukocyte recognition of the extracellular matrix.

PMID- 17446337
TI  - Phase 2 randomized safety and efficacy trial of nebulized denufosol tetrasodium
      in cystic fibrosis.
AB  - RATIONALE: Denufosol tetrasodium is a selective P2Y(2) agonist that enhances
      mucosal hydration and mucus clearance by activating Cl(-) secretion and
      inhibiting epithelial Na(+) transport through a non-cystic fibrosis transmembrane
      conductance regulator mechanism in the lung. OBJECTIVES: To examine the safety
      and efficacy of 28 days of treatment with denufosol compared with placebo in
      patients with mild cystic fibrosis. METHODS: The study was a randomized, double
      blind, multi-center, 28-day, phase 2 clinical trial of denufosol tetrasodium
      inhalation solution (20, 40, or 60 mg) versus placebo (normal saline). Patients
      with screening FEV(1) >or= 75% of predicted normal value and not treated with
      inhaled antibiotics for the past 30 days were randomized to receive one of three
      doses of denufosol or placebo administered three times daily. MEASUREMENTS AND
      MAIN RESULTS: Eighty-nine patients were randomized and received the study drug,
      94% completed the study, and 98% were compliant with dosing. All treatments were
      generally well tolerated, with no dose-response trends observed with respect to
      safety parameters. The most common adverse event was cough (52% of placebo
      patients and 47% of denufosol patients). Five patients discontinued early due to
      adverse events, two on placebo and three on denufosol. Denufosol patients
      (pooling active doses) had significantly higher changes from baseline in FEV(1)
      (P = 0.006), FEF(25%-75%) (P = 0.008), FVC (P = 0.022), and FEV(1)/FVC (P =
      0.047) than placebo patients at the end of the study. CONCLUSIONS: Denufosol
      administered three times daily for 28 days appeared to be safe and well tolerated
      in this population with mild cystic fibrosis and provided preliminary evidence of
      potential benefit in lung function.

PMID- 17446338
TI  - Lung function growth in children with long-term exposure to air pollutants in
      Mexico City.
AB  - RATIONALE: Although short-term exposure to air pollution has been associated with
      acute, reversible lung function decrements, the impact of long-term exposure has
      not been well established. OBJECTIVES: To evaluate the association between long
      term exposure to ozone (O(3)), particulate matter less than 10 mum in diameter
      (PM(10)), and nitrogen dioxide (NO(2)) and lung function growth in Mexico City
      schoolchildren. METHODS: A dynamic cohort of 3,170 children aged 8 years at
      baseline was followed from April 23, 1996, through May 19, 1999. The children
      attended 39 randomly selected elementary schools located near 10 air quality
      monitoring stations and were visited every 6 months. Statistical analyses were
      performed using general linear mixed models. MEASUREMENTS AND MAIN RESULTS: After
      adjusting for acute exposure and other potential confounding factors, deficits in
      FVC and FEV(1) growth over the 3-year follow-up period were significantly
      associated with exposure to O(3), PM(10), and NO(2). In multipollutant models, an
      interquartile range (IQR) increase in mean O(3) concentration (IQR, 11.3 ppb) was
      associated with an annual deficit in FEV(1) of 12 ml in girls and 4 ml in boys,
      an IQR range (IQR, 36.4 microg/m(3)) increase in PM(10) with an annual deficit in
      FEV(1) of 11 ml in girls and 15 ml in boys, and an IQR range (IQR, 12.0 ppb)
      increase in NO(2) with an annual deficit in FEV(1) of 30 ml in girls and 25 ml in
      boys. CONCLUSIONS: We conclude that long-term exposure to O(3), PM(10), and NO(2)
      is associated with a deficit in FVC and FEV(1) growth among schoolchildren living
      in Mexico City.

PMID- 17446339
TI  - Effect of oxygen on health quality of life in patients with chronic obstructive
      pulmonary disease with transient exertional hypoxemia.
AB  - RATIONALE: Ambulatory oxygen improves acute exercise performance in people with
      chronic obstructive pulmonary disease (COPD). This improvement may not translate
      into symptomatic benefit for patients during activities of daily living.
      OBJECTIVES: We undertook a series of individual randomized controlled trials (N
      of-1 RCTs) to measure the effect of oxygen in patients with COPD who do not meet
      criteria for mortality reduction with long-term oxygen therapy. METHODS: Twenty
      seven patients completed blinded N-of-1 RCTs, each comprising three pairs of 2
      week home treatment periods, with oxygen provided during one period of each pair
      and a placebo mixture during the other. MEASUREMENTS AND MAIN RESULTS: Patients
      completed the Chronic Respiratory Questionnaire (CRQ), the St. George's
      Respiratory Questionnaire, and a home five-minute-walk test at the end of each
      period. We defined a positive response as a CRQ dyspnea score greater (less
      dyspnea) on oxygen than placebo during all three pairs of treatment periods, with
      a difference >or= 0.5 inches for at least two treatment pairs. Oxygen
      significantly increased the five-minute-walk test (427 vs. 412 steps, p = 0.04).
      Two of 27 patients met the responder criteria. Among the whole group, neither the
      CRQ nor the St. George's Respiratory Questionnaire showed any statistical or
      clinical differences between oxygen and placebo. CONCLUSIONS: This study does not
      support the general application of long-term ambulatory oxygen therapy for
      patients with COPD who do not meet criteria for mortality reduction with long
      term oxygen therapy. N-of-1 RCTs can identify patients who may benefit.

PMID- 17446341
TI  - One swallow does not make a summer: can herpes simplex virus-1 cause pneumonia
      and acute lung injury?

PMID- 17446340
TI  - Persistent endothelial dysfunction in humans after diesel exhaust inhalation.
AB  - RATIONALE: Exposure to combustion-derived air pollution is associated with an
      early (1-2 h) and sustained (24 h) rise in cardiovascular morbidity and
      mortality. We have previously demonstrated that inhalation of diesel exhaust
      causes an immediate (within 2 h) impairment of vascular and endothelial function
      in humans. OBJECTIVES: To investigate the vascular and systemic effects of diesel
      exhaust in humans 24 hours after inhalation. METHODS: Fifteen healthy men were
      exposed to diesel exhaust (particulate concentration, 300 microg/m(3)) or
      filtered air for 1 hour in a double-blind, randomized, crossover study. Twenty
      four hours after exposure, bilateral forearm blood flow, and inflammatory and
      fibrinolytic markers were measured before and during unilateral intrabrachial
      bradykinin (100-1,000 pmol/min), acetylcholine (5-20 microg/min), sodium
      nitroprusside (2-8 microg/min), and verapamil (10-100 microg/min) infusions.
      MEASUREMENTS AND MAIN RESULTS: Resting forearm blood flow, blood pressure, and
      basal fibrinolytic markers were similar 24 hours after either exposure. Diesel
      exhaust increased plasma cytokine concentrations (tumor necrosis factor-alpha and
      interleukin-6, p < 0.05 for both) but appeared to reduce acetylcholine (p =
      0.01), and bradykinin (p = 0.08) induced forearm vasodilatation. In contrast,
      there were no differences in either endothelium-independent (sodium nitroprusside
      and verapamil) vasodilatation or bradykinin-induced acute plasma tissue
      plasminogen activator release. CONCLUSIONS: Twenty-four hours after diesel
      exposure, there is a selective and persistent impairment of endothelium-dependent
      vasodilatation that occurs in the presence of mild systemic inflammation. These
      findings suggest that combustion-derived air pollution may have important
      systemic and adverse vascular effects for at least 24 hours after exposure.

PMID- 17446342
TI  - Unexpected failure of anti-tumor necrosis factor therapy in chronic obstructive
      pulmonary disease.

PMID- 17446344
TI  - A novel host defense system of airways is defective in cystic fibrosis: update.

PMID- 17446343
TI  - Update in lung cancer 2006.

PMID- 17446345
TI  - Specific IgE against recombinant allergens in allergic bronchopulmonary
      aspergillosis.

PMID- 17446346
TI  - Computer-driven protocolized weaning from mechanical ventilation.

PMID- 17446347
TI  - The spectrum of mutations in the PCFT gene, coding for an intestinal folate
      transporter, that are the basis for hereditary folate malabsorption.
AB  - Hereditary folate malabsorption (HFM) is a rare autosomal recessive disorder
      caused by impaired intestinal folate absorption and impaired folate transport
      into the central nervous system. Recent studies in 1 family revealed that the
      molecular basis for this disorder is a loss-of-function mutation in the PCFT gene
      encoding a proton-coupled folate transporter. The current study broadens the
      understanding of the spectrum of alterations in the PCFT gene associated with HFM
      in 5 additional patients. There was no racial, ethnic, or sex pattern. A total of
      4 different homozygous mutations were detected in 4 patients; 2 heterozygous
      mutations were identified in the fifth patient. Mutations involved 4 of the 5
      exons, all at highly conserved amino acid residues. A total of 4 of the mutated
      transporters resulted in a complete loss of transport function, primarily due to
      decreased protein stability and/or defects in membrane trafficking, while 2 of
      the mutated carriers manifested residual function. Folate transport at low pH was
      markedly impaired in transformed lymphocytes from 2 patients. These findings
      further substantiate the role that mutations in PCFT play in the pathogenesis of
      HFM and will make possible rapid diagnosis and treatment of this disorder in
      infants, and prenatal diagnosis in families that carry a mutated gene.

PMID- 17446348
TI  - Flt3-dependent transformation by inactivating c-Cbl mutations in AML.
AB  - In acute myeloid leukemia (AML), mutational activation of the receptor tyrosine
      kinase (RTK) Flt3 is frequently involved in leukemic transformation. However,
      little is known about a possible role of highly expressed wild-type Flt3 in AML.
      The proto-oncogene c-Cbl is an important regulator of RTK signaling, acting
      through its ubiquitin ligase activity and as a platform for several signaling
      adaptor molecules. Here, we analyzed the role of c-Cbl in Flt3 signal
      transduction and myeloid transformation. C-Cbl physically interacted with Flt3
      and was tyrosine phosphorylated in the presence of Flt3-ligand (FL).
      Overexpression of a dominant-negative form of c-Cbl (Cbl-70Z) inhibited FL
      induced Flt3 ubiquitylation and internalization, indicating involvement of c-Cbl
      in Flt3 signaling. DNA sequencing of AML bone marrow revealed a case with a c-Cbl
      point mutation (Cbl-R420Q). Cbl-R420Q inhibited Flt3 internalization and
      ubiquitylation. Coexpression of Cbl-R420Q or Cbl-70Z with Flt3 induced cytokine
      independent growth and survival of 32Dcl3 cells in the absence of FL. Also, the
      mutant Cbl proteins altered the amplitude and duration of Flt3-dependent
      signaling events. Our results indicate an important role of Cbl proteins in Flt3
      signal modulation. Also, the data suggest a novel mechanism of leukemic
      transformation in AML by mutational inactivation of negative RTK regulators.

PMID- 17446349
TI  - Mortality rates, life expectancy, and causes of death in people with hemophilia A
      or B in the United Kingdom who were not infected with HIV.
AB  - Since the 1970s, mortality in the hemophilia population has been dominated by
      human immunodeficiency virus (HIV) and few reports have described mortality in
      uninfected individuals. This study presents mortality in 6018 people with
      hemophilia A or B in the United Kingdom during 1977 to 1998 who were not infected
      with HIV, with follow-up until January 1, 2000. Given disease severity and factor
      inhibitor status, all-cause mortality did not differ significantly between
      hemophilia A and hemophilia B. In severe hemophilia, all-cause mortality did not
      change significantly during 1977 to 1999. During this period, it exceeded
      mortality in the general population by a factor of 2.69 (95% confidence interval
      [CI]: 2.37-3.05), and median life expectancy in severe hemophilia was 63 years.
      In moderate/mild hemophilia, all-cause mortality did not change significantly
      during 1985 to 1999, and median life expectancy was 75 years. Compared with
      mortality in the general population, mortality from bleeding and its
      consequences, and from liver diseases and Hodgkin disease, was increased, but for
      ischemic heart disease it was lower, at only 62% (95% CI: 51%-76%) of general
      population rates, and for 14 other specific causes it did not differ
      significantly from general population rates. There was no evidence of any death
      from variant Creutzfeldt-Jakob disease or from conditions that could be confused
      with it.

PMID- 17446350
TI  - Mast cells are crucial for early inflammation, migration of Langerhans cells, and
      CTL responses following topical application of TLR7 ligand in mice.
AB  - Until recently, IgE-activated mast cells have been regarded merely as effector
      cells of adaptive immune responses, involved in allergic reactions and mucosal
      immunity to parasites. Herein, we report that murine dermal mast cells, activated
      by local administration of a cream containing the synthetic TLR7 ligand
      imiquimod, are essential to initiate an early inflammatory reaction. The mast
      cell-derived cytokines TNF-alpha and IL-1beta play an important role in this
      process. Furthermore, TLR7-activated mast cells are also able to promote the
      emigration of Langerhans cells, which partly depends on the expression of mast
      cell-derived IL-1beta. We have previously shown that TLR7 ligation enhances
      transcutaneous immunization evoked by topical application of vaccine antigens to
      the skin, a procedure that directly targets skin-resident antigen-presenting
      cells. Consequently, we now demonstrate here that the capacity to mount a peptide
      specific cytotoxic T-lymphocyte response following transcutaneous immunization
      using imiquimod as adjuvant is severely impaired in mast-cell-deficient mice.
      Thus, these findings demonstrate the potent versatility of alternatively
      activated mast cells at the interface of innate and adaptive immunity.

PMID- 17446351
TI  - Hd3a protein is a mobile flowering signal in rice.
AB  - Florigen, the mobile signal that moves from an induced leaf to the shoot apex and
      causes flowering, has eluded identification since it was first proposed 70 years
      ago. Understanding the nature of the mobile flowering signal would provide a key
      insight into the molecular mechanism of floral induction. Recent studies suggest
      that the Arabidopsis FLOWERING LOCUS T (FT) gene is a candidate for encoding
      florigen. We show that the protein encoded by Hd3a, a rice ortholog of FT, moves
      from the leaf to the shoot apical meristem and induces flowering in rice. These
      results suggest that the Hd3a protein may be the rice florigen.

PMID- 17446352
TI  - Developmentally regulated piRNA clusters implicate MILI in transposon control.
AB  - Nearly half of the mammalian genome is composed of repeated sequences. In
      Drosophila, Piwi proteins exert control over transposons. However, mammalian Piwi
      proteins, MIWI and MILI, partner with Piwi-interacting RNAs (piRNAs) that are
      depleted of repeat sequences, which raises questions about a role for mammalian
      Piwi's in transposon control. A search for murine small RNAs that might program
      Piwi proteins for transposon suppression revealed developmentally regulated piRNA
      loci, some of which resemble transposon master control loci of Drosophila. We
      also find evidence of an adaptive amplification loop in which MILI catalyzes the
      formation of piRNA 5' ends. Mili mutants derepress LINE-1 (L1) and intracisternal
      A particle and lose DNA methylation of L1 elements, demonstrating an
      evolutionarily conserved role for PIWI proteins in transposon suppression.

PMID- 17446353
TI  - FT protein movement contributes to long-distance signaling in floral induction of
      Arabidopsis.
AB  - In plants, seasonal changes in day length are perceived in leaves, which initiate
      long-distance signaling that induces flowering at the shoot apex. The identity of
      the long-distance signal has yet to be determined. In Arabidopsis, activation of
      FLOWERING LOCUS T (FT) transcription in leaf vascular tissue (phloem) induces
      flowering. We found that FT messenger RNA is required only transiently in the
      leaf. In addition, FT fusion proteins expressed specifically in phloem cells move
      to the apex and move long distances between grafted plants. Finally, we provide
      evidence that FT does not activate an intermediate messenger in leaves. We
      conclude that FT protein acts as a long-distance signal that induces Arabidopsis
      flowering.

PMID- 17446354
TI  - Blastocyst axis is specified independently of early cell lineage but aligns with
      the ZP shape.
AB  - The mechanisms controlling the establishment of the embryonic-abembryonic (E-Ab)
      axis of the mammalian blastocyst are controversial. We used in vitro time-lapse
      imaging and in vivo lineage labeling to provide evidence that the E-Ab axis of
      the mouse blastocyst is generated independently of early cell lineage. Rather,
      both the boundary between two-cell blastomeres and the E-Ab axis of the
      blastocyst align relative to the ellipsoidal shape of the zona pellucida (ZP), an
      extraembryonic structure. Lack of correlation between cell lineage and the E-Ab
      axis can be explained by the rotation of the embryo within the ZP.

PMID- 17446355
TI  - Regolith migration and sorting on asteroid Itokawa.
AB  - High-resolution images of the surface of asteroid Itokawa from the Hayabusa
      mission reveal it to be covered with unconsolidated millimeter-sized and larger
      gravels. Locations and morphologic characteristics of this gravel indicate that
      Itokawa has experienced considerable vibrations, which have triggered global
      scale granular processes in its dry, vacuum, microgravity environment. These
      processes likely include granular convection, landslide-like granular migrations,
      and particle sorting, resulting in the segregation of the fine gravels into areas
      of potential lows. Granular processes become major resurfacing processes because
      of Itokawa's small size, implying that they can occur on other small asteroids
      should those have regolith.

PMID- 17446356
TI  - Free-range eggs?

PMID- 17446358
TI  - Oil resources. The looming oil crisis could arrive uncomfortably soon.

PMID- 17446360
TI  - Physics. Colliding clouds may hone physical constants.

PMID- 17446357
TI  - Plant science. Long-sought plant flowering signal unmasked, again.

PMID- 17446359
TI  - Neuroscience. Astrocytes secrete substance that kills motor neurons in ALS.

PMID- 17446361
TI  - Psychopharmacology. Study questions antidepressant risks.

PMID- 17446362
TI  - Epidemiology. Iraq mortality study authors release data, but only to some.

PMID- 17446363
TI  - NIH budget. Boom and bust.

PMID- 17446364
TI  - NIH budget. Peer review under stress.

PMID- 17446365
TI  - Infectious disease. Polio: no cheap way out.

PMID- 17446366
TI  - Infectious disease. Moderate success for new polio vaccine.

PMID- 17446367
TI  - American Association of Physical Anthropologists meeting. European skin turned
      pale only recently, gene suggests.

PMID- 17446368
TI  - American Association of Physical Anthropologists meeting. Gorillas' hidden
      history revealed.

PMID- 17446369
TI  - American Association of Physical Anthropologists meeting. Adapting to Tibet's
      thin air.

PMID- 17446370
TI  - Retraction.

PMID- 17446371
TI  - A thank you from Tulane University.

PMID- 17446372
TI  - Astrobiology and missions at NASA.

PMID- 17446373
TI  - Oocyte donation for stem cell research.

PMID- 17446375
TI  - Comment on "Ongoing adaptive evolution of ASPM, a brain size determinant in Homo
      sapiens".
AB  - Mekel-Bobrov et al. (Reports, 9 September 2005, p. 1720) suggested that ASPM, a
      gene associated with microcephaly, underwent natural selection within the last
      500 to 14,100 years. Their analyses based on comparison with computer simulations
      indicated that ASPM had an unusual pattern of variation. However, when we compare
      ASPM empirically to a large number of other loci, its variation is not unusual
      and does not support selection.

PMID- 17446376
TI  - Environment. The burning issue.

PMID- 17446377
TI  - Plant science. SCARECROWs at the border.

PMID- 17446378
TI  - Biochemistry. An ancient and intimate partnership.

PMID- 17446379
TI  - Planetary science. A new spin on Saturn's rotation.

PMID- 17446380
TI  - Ecology. Rapid domestication of marine species.

PMID- 17446381
TI  - Evolution. Aging and sexual conflict.

PMID- 17446383
TI  - Melting opposition to frozen eggs.

PMID- 17446384
TI  - A close look at urbisexuality.

PMID- 17446385
TI  - Germ versus soma decisions: lessons from flies and worms.
AB  - The early embryo is formed by the fusion of two germ cells that must generate not
      only all of the nonreproductive somatic cell types of its body but also the germ
      cells for the next generation. Therefore, embryo cells face a crucial decision:
      whether to develop as germ or soma. How is this fundamental decision made and
      germ cell fate maintained during development? Studies in the nematode worm
      Caenorhabditis elegans and fruit fly Drosophila identify some of the decision
      making strategies, including segregation of a specialized germ plasm and global
      transcriptional regulation.

PMID- 17446386
TI  - Germ cell specification in mice.
AB  - Specification of germ cells in mice occurs relatively late in embryonic
      development. It is initiated by signals that induce expression of Blimp1, a key
      regulator of the germ cell, in a few epiblast cells of early postimplantation
      embryos. Blimp1 represses the incipient somatic program in these cells and
      promotes progression toward the germ cell fate. Blimp1 may also have a role in
      the maintenance of early germ cell characteristics by ensuring their escape from
      the somatic fate as well as possible reversion to pluripotent stem cells.

PMID- 17446387
TI  - piRNAs in the germ line.
AB  - Small noncoding RNAs have emerged as potent regulators of gene expression at both
      transcriptional and posttranscriptional levels. Recently, a class of small RNAs
      that interact with Piwi proteins has been discovered in the mammalian germ line
      and Drosophila. These Piwi-interacting RNAs (piRNAs) represent a distinct small
      RNA pathway.

PMID- 17446388
TI  - Epigenetic decisions in mammalian germ cells.
AB  - Specific sequences are designated for de novo DNA methylation at CpG
      dinucleotides in mammalian germ cells. The result is the long-term
      transcriptional silencing of the methylated sequences, most of which are
      retrotransposons and CpG-rich sequences associated with imprinted genes. There is
      profound sexual dimorphism in both the nature of the sequences that undergo de
      novo methylation in germ cells and in the mechanism by which de novo methylation
      is regulated. The restriction of future gene expression by the imposition of
      heritable methylation patterns in germ cell genomes is characteristic of mammals
      but is rare in other taxa.

PMID- 17446389
TI  - The mysteries of sexual identity. The germ cell's perspective.
AB  - Animal germ cells differentiate as sperm or eggs, depending on their sex. Somatic
      signals tell germ cells whether they reside in a male or female body, but how do
      germ cells interpret those external cues to acquire their own sexual identity? A
      critical aspect of a germ cell's sexual puzzle is that the sperm/egg decision is
      closely linked to the cell-cycle decision between mitosis and meiosis. Molecular
      studies have begun to tease apart the regulators of both decisions, an essential
      step toward understanding the regulatory logic of this fundamental question of
      germ cell biology.

PMID- 17446390
TI  - Male and female Drosophila germline stem cells: two versions of immortality.
AB  - Drosophila male and female germline stem cells (GSCs) are sustained by niches and
      regulatory pathways whose common principles serve as models for understanding
      mammalian stem cells. Despite striking cellular and genetic similarities that
      suggest a common evolutionary origin, however, male and female GSCs also display
      important differences. Comparing these two stem cells and their niches in detail
      is likely to reveal how a common heritage has been adapted to the differing
      requirements of male and female gamete production.

PMID- 17446391
TI  - Male germline stem cells: from mice to men.
AB  - The production of functional male gametes is dependent on the continuous activity
      of germline stem cells. The availability of a transplantation assay system to
      unequivocally identify male germline stem cells has allowed their in vitro
      culture, cryopreservation, and genetic modification. Moreover, the system has
      enabled the identification of conditions and factors involved in stem cell self
      renewal, the foundation of spermatogenesis, and the production of spermatozoa.
      The increased knowledge about these cells is also of great potential practical
      value, for example, for the possible cryopreservation of stem cells from boys
      undergoing treatment for cancer to safeguard their germ line.

PMID- 17446392
TI  - The maternal-zygotic transition: death and birth of RNAs.
AB  - Maternal gene products drive early development when the newly formed embryo is
      transcriptionally inactive. During the maternal-zygotic transition, embryonic
      transcription is initiated and many maternal RNAs are degraded. Multiple
      mechanisms regulate the birth of zygotic RNAs and the death of maternal RNAs.
      Genome activation appears to rely in part on the sequestration of transcriptional
      repressors by the exponentially increasing amount of DNA during cleavage
      divisions. Maternal RNA degradation is induced by the binding of proteins and
      microRNAs to the 3' untranslated region of target RNAs.

PMID- 17446393
TI  - Regulation of the oocyte-to-zygote transition.
AB  - Oocytes, the female germ cells, contain all the messenger RNAs necessary to start
      a new life but typically wait until fertilization to begin development. The
      transition from oocyte to fertilized egg (zygote) involves many changes,
      including protein synthesis, protein and RNA degradation, and organelle
      remodeling. These changes occur concurrently with the meiotic divisions that
      produce the haploid maternal genome. Accumulating evidence indicates that the
      cell-cycle regulators that control the meiotic divisions also regulate the many
      changes that accompany the oocyte-to-zygote transition. We suggest that the
      meiotic machinery functions as an internal pacemaker that propels oocytes toward
      embryogenesis.

PMID- 17446394
TI  - Gametes from embryonic stem cells: a cup half empty or half full?
AB  - When first reported 4 years ago, gametogenesis from embryonic stem (ES) cells
      promised an accessible in vitro model to facilitate molecular analysis of the
      germ lineage. Formation of primordial germ cells is robust, but terminal
      gametogenesis remains inefficient and doubts about gamete function persist.
      Although useful for research, clinical use of ES cell-derived gametes appears a
      distant prospect.

PMID- 17446395
TI  - Temperature sex reversal implies sex gene dosage in a reptile.
AB  - Sex in reptiles is determined by genes on sex chromosomes or by incubation
      temperature. Previously these two modes were thought to be distinct, yet we show
      that high incubation temperatures reverse genotypic males (ZZ) to phenotypic
      females in a lizard with ZZ and ZW sex chromosomes. Thus, the W chromosome is not
      necessary for female differentiation. Sex determination is probably via a dosage
      sensitive male-determining gene on the Z chromosome that is inactivated by
      extreme temperatures. Our data invite a novel hypothesis for the evolution of
      temperature-dependent sex determination (TSD) and suggest that sex chromosomes
      may exist in many TSD reptiles.

PMID- 17446396
TI  - An evolutionarily conserved mechanism delimiting SHR movement defines a single
      layer of endodermis in plants.
AB  - Intercellular protein movement plays a critical role in animal and plant
      development. SHORTROOT (SHR) is a moving transcription factor essential for
      endodermis specification in the Arabidopsis root. Unlike diffusible animal
      morphogens, which form a gradient across multiple cell layers, SHR movement is
      limited to essentially one cell layer. However, the molecular mechanism is
      unknown. We show that SCARECROW (SCR) blocks SHR movement by sequestering it into
      the nucleus through protein-protein interaction and a safeguard mechanism that
      relies on a SHR/SCR-dependent positive feedback loop for SCR transcription. Our
      studies with SHR and SCR homologs from rice suggest that this mechanism is
      evolutionarily conserved, providing a plausible explanation why nearly all plants
      have a single layer of endodermis.

PMID- 17446397
TI  - Nonequilibrium phase transitions in cuprates observed by ultrafast electron
      crystallography.
AB  - Nonequilibrium phase transitions, which are defined by the formation of
      macroscopic transient domains, are optically dark and cannot be observed through
      conventional temperature- or pressure-change studies. We have directly determined
      the structural dynamics of such a nonequilibrium phase transition in a cuprate
      superconductor. Ultrafast electron crystallography with the use of a tilted
      optical geometry technique afforded the necessary atomic-scale spatial and
      temporal resolutions. The observed transient behavior displays a notable
      "structural isosbestic" point and a threshold effect for the dependence of c-axis
      expansion (Deltac) on fluence (F), with Deltac/F = 0.02 angstrom/(millijoule per
      square centimeter). This threshold for photon doping occurs at approximately 0.12
      photons per copper site, which is unexpectedly close to the density (per site) of
      chemically doped carriers needed to induce superconductivity.

PMID- 17446398
TI  - Creep-resistant, Al2O3-forming austenitic stainless steels.
AB  - A family of inexpensive, Al2O3-forming, high-creep strength austenitic stainless
      steels has been developed. The alloys are based on Fe-20Ni-14Cr-2.5Al weight
      percent, with strengthening achieved through nanodispersions of NbC. These alloys
      offer the potential to substantially increase the operating temperatures of
      structural components and can be used under the aggressive oxidizing conditions
      encountered in energy-conversion systems. Protective Al2O3 scale formation was
      achieved with smaller amounts of aluminum in austenitic alloys than previously
      used, provided that the titanium and vanadium alloying additions frequently used
      for strengthening were eliminated. The smaller amounts of aluminum permitted
      stabilization of the austenitic matrix structure and made it possible to obtain
      excellent creep resistance. Creep-rupture lifetime exceeding 2000 hours at 750
      degrees C and 100 megapascals in air, and resistance to oxidation in air with 10%
      water vapor at 650 degrees and 800 degrees C, were demonstrated.

PMID- 17446399
TI  - Synthesis of ultra-incompressible superhard rhenium diboride at ambient pressure.
AB  - The quest to create superhard materials rarely strays from the use of high
      pressure synthetic methods, which typically require gigapascals of applied
      pressure. We report that rhenium diboride (ReB2), synthesized in bulk quantities
      via arc-melting under ambient pressure, rivals materials produced with high
      pressure methods. Microindentation measurements on ReB2 indicated an average
      hardness of 48 gigapascals under an applied load of 0.49 newton, and scratch
      marks left on a diamond surface confirmed its superhard nature. Its
      incompressibility along the c axis was equal in magnitude to the linear
      incompressibility of diamond. In situ high-pressure x-ray diffraction
      measurements yielded a bulk modulus of 360 gigapascals, and radial diffraction
      indicated that ReB2 is able to support a remarkably high differential stress.
      This combination of properties suggests that this material may find applications
      in cutting when the formation of carbides prevents the use of traditional
      materials such as diamond.

PMID- 17446400
TI  - Facile splitting of hydrogen and ammonia by nucleophilic activation at a single
      carbon center.
AB  - In possessing a lone pair of electrons and an accessible vacant orbital, singlet
      carbenes resemble transition metal centers and thus could potentially mimic their
      chemical behavior. Although singlet di(amino)carbenes are inert toward
      dihydrogen, it is shown that more nucleophilic and electrophilic
      (alkyl)(amino)carbenes can activate H2 under mild conditions, a reaction that has
      long been known for transition metals. However, in contrast to transition metals
      that act as electrophiles toward dihydrogen, these carbenes primarily behave as
      nucleophiles, creating a hydride-like hydrogen, which then attacks the positively
      polarized carbon center. This nucleophilic behavior allows these carbenes to
      activate NH3 as well, a difficult task for transition metals because of the
      formation of Lewis acid-base adducts.

PMID- 17446401
TI  - Raman-assisted crystallography reveals end-on peroxide intermediates in a nonheme
      iron enzyme.
AB  - Iron-peroxide intermediates are central in the reaction cycle of many iron
      containing biomolecules. We trapped iron(III)-(hydro)peroxo species in crystals
      of superoxide reductase (SOR), a nonheme mononuclear iron enzyme that scavenges
      superoxide radicals. X-ray diffraction data at 1.95 angstrom resolution and Raman
      spectra recorded in crystallo revealed iron-(hydro)peroxo intermediates with the
      (hydro)peroxo group bound end-on. The dynamic SOR active site promotes the
      formation of transient hydrogen bond networks, which presumably assist the
      cleavage of the iron-oxygen bond in order to release the reaction product,
      hydrogen peroxide.

PMID- 17446402
TI  - Crystal structures of Fe2+ dioxygenase superoxo, alkylperoxo, and bound product
      intermediates.
AB  - We report the structures of three intermediates in the O2 activation and
      insertion reactions of an extradiol ring-cleaving dioxygenase. A crystal of Fe2+
      containing homoprotocatechuate 2,3-dioxygenase was soaked in the slow substrate 4
      nitrocatechol in a low O2 atmosphere. The x-ray crystal structure shows that
      three different intermediates reside in different subunits of a single
      homotetrameric enzyme molecule. One of these is the key substrate-alkylperoxo
      Fe2+ intermediate, which has been predicted, but not structurally characterized,
      in an oxygenase. The intermediates define the major chemical steps of the
      dioxygenase mechanism and point to a general mechanistic strategy for the diverse
      2-His-1-carboxylate enzyme family.

PMID- 17446403
TI  - Neuronal competition and selection during memory formation.
AB  - Competition between neurons is necessary for refining neural circuits during
      development and may be important for selecting the neurons that participate in
      encoding memories in the adult brain. To examine neuronal competition during
      memory formation, we conducted experiments with mice in which we manipulated the
      function of CREB (adenosine 3',5'-monophosphate response element-binding protein)
      in subsets of neurons. Changes in CREB function influenced the probability that
      individual lateral amygdala neurons were recruited into a fear memory trace. Our
      results suggest a competitive model underlying memory formation, in which
      eligible neurons are selected to participate in amemorytrace as a function of
      their relative CREB activity at the time of learning.

PMID- 17446404
TI  - Temporal differences in the influence of ischemic factors and deformation on the
      metabolism of engineered skeletal muscle.
AB  - Prolonged periods of tissue compression may lead to the development of pressure
      ulcers, some of which may originate in, for example, skeletal muscle tissue and
      progress underneath intact skin, representing deep tissue injury. Their etiology
      is multifactorial and the interaction between individual causal factors and their
      relative importance remain unknown. The present study addressed the relative
      contributions of deformation and ischemic factors to altered metabolism and
      viability. Engineered muscle tissue was prepared as previously detailed (14) and
      subjected to a combination of factors including 0% oxygen, lactic acid
      concentrations resulting in pH from 5.3 to 7.4, 34% compression, and low glucose
      levels. Deformation had an immediate effect on tissue viability {[3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay}, which
      increased with time. By contrast, hypoxia evoked metabolic responses (glucose and
      lactate levels) within 24 h, but viability was only reduced after 48 h. In
      addition, lactic acidification downregulated tissue metabolism up to an acid
      concentration ( approximately 23 mM) where metabolism was arrested and cell death
      enhanced. A similar tissue response was observed during glucose deprivation,
      which, at negligible concentration, resulted in both a cessation of metabolic
      activity and a reduction in cell viability. The combination of results suggests
      that in a short-term (<24 h) deformation, extreme acidification and glucose
      deprivation increased the level of cell death. By contrast, nonextreme
      acidification and hypoxia influenced tissue metabolism, but not the development
      of cell death. These data provide more insight into how compression-induced
      factors can lead to the onset of deep tissue injury.

PMID- 17446405
TI  - Effects of short-term vibration and hypoxia during high-intensity cycling
      exercise on circulating levels of angiogenic regulators in humans.
AB  - This study aimed to investigate the biological response to hypoxia as a stimulus,
      as well as exercise- and vibration-induced shear stress, which is known to induce
      angiogenesis. Twelve male cyclists (27.8 +/- 5.4 yr) participated in this study.
      Each subject completed four cycle training sessions under normal conditions (NC)
      without vibration, NC with vibration, normobaric hypoxic conditions (HC) without
      vibration, and HC with vibration. Each session lasted 90 min, and sessions were
      held at weekly intervals in a randomized order. Five blood samples (pretraining
      and 0 h post-, 0.5 h post-, 1 h post-, and 4 h posttraining) were taken from each
      subject at each training session. Hypoxia was induced by a normobaric hypoxic
      chamber with an altitude of 2,500 m. The mechanical forces (cycling with or
      without vibration) were induced by a cycling ergometer. The parameters VEGF,
      endostatin, and matrix metalloproteinases (MMPs) were analyzed using the ELISA
      method. VEGF showed a significant increase immediately after the exercise only
      with exogenously induced vibrations, as calculated with separate ANOVA analysis.
      Endostatin increased after training under all conditions. Western blot analysis
      was performed for the determination of endostatin corresponding to the 22-kDa
      cleavage product of collagen XVIII. This demonstrated elevated protein content
      for endostatin at 0 h postexercise. MMP-2 increased in three of the four training
      conditions. The exception was NC with vibration. MMP-9 reached its maximum level
      at 4 h postexercise. In conclusion, the results support the contention that
      mechanical stimuli differentially influence factors involved in the induction of
      angiogenesis. These findings may contribute to a broader understanding of
      angiogenesis.

PMID- 17446406
TI  - Alveolar macrophage depletion is associated with increased surfactant pool sizes
      in adult rats.
AB  - Pulmonary surfactant is a lipid-protein material that is essential for normal
      lung function. Maintaining normal and consistent alveolar amounts of surfactant
      is in part dependent on clearance of surfactant by alveolar macrophages (AM). The
      present study utilized a rat model of AM depletion to determine the impact on
      surfactant pool sizes and function over time. Male Sprague-Dawley rats were
      anesthetized and intratracheally instilled with PBS-liposomes (PBS-L) or
      dichloromethylene diphosphonic acid (DMDP) containing liposomes (DMDP-L) and were
      killed at various time points up to 21 days for compliance measurements, AM cell
      counts, and surfactant analysis. AM numbers were significantly decreased 1, 2,
      and 3 days after instillation in DMDP-L vs. PBS-L, with 72% depletion at 3 days.
      AM numbers returned to normal levels by 5 days. In DMDP-L rats, there was a rapid
      increase in surfactant-phospholipid pools, showing a ninefold increase in the
      amount of surfactant in the lavage 3 days after liposome instillation. Surfactant
      accumulation progressed up to 7 days, with pools normalizing by 21 days. The
      increase in surfactant was due to increases in both subfractions of surfactant,
      the large aggregates (LA) and small aggregates. Surfactant protein A levels,
      relative to LA phospholipids, were not increased. There was a decreased extent of
      surfactant conversion in vitro for LA from DMDP-L rats compared with controls. It
      is concluded that the procedure of AM depletion significantly affects surfactant
      metabolism. The increased endogenous surfactant must be considered when utilizing
      the AM depletion model to study the role of these cells during lung insults.

PMID- 17446407
TI  - Adaptations in the activation of human skeletal muscle induced by short-term
      isometric resistance training.
AB  - This study employed longitudinal measures of evoked spinal reflex responses
      (Hoffman reflex, V wave) to investigate changes in the activation of muscle and
      to determine if there are "linked" neural adaptations in the motor pathway
      following isometric resistance training. Twenty healthy, sedentary males were
      randomly assigned to either the trained (n = 10) or control group (n = 10). The
      training protocol consisted of 12 sessions of isometric resistance training of
      the plantar flexor muscles over a 4-wk period. All subjects were tested prior to
      and after the 4-wk period. To estimate changes in spinal excitability, soleus
      Hoffman (H) reflex and M wave recruitment curves were produced at rest and during
      submaximal contractions. Recruitment curves were analyzed using the slope method
      (Hslp/Mslp). Modulation of efferent neural drive was assessed through evoked V
      wave responses (V/Mmax) at 50, 75, and 100% maximal voluntary contraction (MVC).
      After 4 weeks, MVC torque increased 20.0 +/- 13.9% (mean +/- SD) in the trained
      group. The increase in MVC was accompanied by significant increases in the rate
      of torque development (42.5 +/- 13.3%), the soleus surface electromyogram (60.7
      +/- 30.8%), voluntary activation (2.8 +/- 0.1%), and the rate of activation (48.7
      +/- 24.3%). Hslp/Mslp was not altered by training; however, V/Mmax increased 57.3
      +/- 34.2% during MVC. These results suggest that increases in MVC observed in the
      first few days of isometric resistance training can be accounted for by an
      increase in the rate of activation at the onset of muscle contraction.
      Augmentation of muscle activation may be due to increased volitional drive from
      supraspinal centers.

PMID- 17446408
TI  - Tendon mechanics: the argument heats up.

PMID- 17446409
TI  - Exercise and inflammation.

PMID- 17446410
TI  - A new class of biophysical models for predicting the probability of decompression
      sickness in scuba diving.
AB  - Interconnected compartmental models have been used for decades in physiology and
      medicine to account for the observed multi-exponential washout kinetics of a
      variety of solutes (including inert gases) both from single tissues and from the
      body as a whole. They are used here as the basis for a new class of biophysical
      probabilistic decompression models. These models are characterized by a
      relatively well-perfused, risk-bearing, central compartment and one or two non
      risk-bearing, relatively poorly perfused, peripheral compartment(s). The
      peripheral compartments affect risk indirectly by diffusive exchange of dissolved
      inert gas with the central compartment. On the basis of the accuracy of their
      respective predictions beyond the calibration regime, the three-compartment
      interconnected models were found to be significantly better than the two
      compartment interconnected models. The former, on the basis of a number of
      criteria, was also better than a two-compartment parallel model used for
      comparative purposes. In these latter comparisons, the models all had the same
      number of fitted parameters (four), were based on linear kinetics, had the same
      risk function, and were calibrated against the same dataset. The interconnected
      models predict that inert gas washout during decompression is relatively fast,
      initially, but slows rapidly with time compared with the more uniform washout
      rate predicted by an independent parallel compartment model. If empirically
      verified, this may have important implications for diving practice.

PMID- 17446411
TI  - Quantitative diffusion tensor MRI-based fiber tracking of human skeletal muscle.
AB  - Diffusion-tensor magnetic resonance imaging (DT-MRI) offers great potential for
      understanding structure-function relationships in human skeletal muscles. The
      purposes of this study were to demonstrate the feasibility of using in vivo human
      DT-MRI fiber tracking data for making pennation angle measurements and to test
      the hypothesis that heterogeneity in the orientation of the tibialis anterior
      (TA) muscle's aponeurosis would lead to heterogeneity in pennation angle. Eight
      healthy subjects (5 male) were studied. T(1)-weighted anatomical MRI and DT-MRI
      data were acquired of the TA muscle. Fibers were tracked from the TA's
      aponeurosis by following the principal eigenvector. The orientations of the
      aponeurosis and muscle fiber tracts in the laboratory frame of reference and the
      orientation of the fiber tracts with respect to the aponeurosis [i.e., the
      pennation angle (theta)] were determined. The muscle fiber orientations, when
      expressed relative to the laboratory frame of reference, did not change as
      functions of superior-to-inferior position. The sagittal and coronal orientations
      of the aponeurosis did not change in practically significant manners either, but
      the aponeurosis' axial orientation changed by approximately 40 degrees . As a
      result, the mean value for theta decreased from 16.3 (SD 6.9) to 11.4 degrees (SD
      5.0) along the muscle's superior-to-inferior direction. The mean value of theta
      was greater in the deep than in the superficial compartment. We conclude that
      pennation angle measurements of human muscle made using DT-MRI muscle fiber
      tracking are feasible and reveal that in the foot-head direction, there is
      heterogeneity in the pennation properties of the human TA muscle.

PMID- 17446412
TI  - Muscle Na+-K+-ATPase activity and isoform adaptations to intense interval
      exercise and training in well-trained athletes.
AB  - The Na+ -K+ -ATPase enzyme is vital in skeletal muscle function. We investigated
      the effects of acute high-intensity interval exercise, before and following high
      intensity training (HIT), on muscle Na+ -K+ -ATPase maximal activity, content,
      and isoform mRNA expression and protein abundance. Twelve endurance-trained
      athletes were tested at baseline, pretrain, and after 3 wk of HIT (posttrain),
      which comprised seven sessions of 8 x 5-min interval cycling at 80% peak power
      output. Vastus lateralis muscle was biopsied at rest (baseline) and both at rest
      and immediately postexercise during the first (pretrain) and seventh (posttrain)
      training sessions. Muscle was analyzed for Na+ -K+ -ATPase maximal activity (3-O
      MFPase), content ([3H]ouabain binding), isoform mRNA expression (RT-PCR), and
      protein abundance (Western blotting). All baseline-to-pretrain measures were
      stable. Pretrain, acute exercise decreased 3-O-MFPase activity [12.7% (SD 5.1), P
      < 0.05], increased alpha1, alpha2, and alpha3 mRNA expression (1.4-, 2.8-, and
      3.4-fold, respectively, P < 0.05) with unchanged beta-isoform mRNA or protein
      abundance of any isoform. In resting muscle, HIT increased (P < 0.05) 3-O-MFPase
      activity by 5.5% (SD 2.9), and alpha3 and beta3 mRNA expression by 3.0- and 0.5
      fold, respectively, with unchanged Na+ -K+ -ATPase content or isoform protein
      abundance. Posttrain, the acute exercise induced decline in 3-O-MFPase activity
      and increase in alpha1 and alpha3 mRNA each persisted (P < 0.05); the
      postexercise 3-O-MFPase activity was also higher after HIT (P < 0.05). Thus HIT
      augmented Na+ -K+ -ATPase maximal activity despite unchanged total content and
      isoform protein abundance. Elevated Na+ -K+ -ATPase activity postexercise may
      contribute to reduced fatigue after training. The Na+ -K+ -ATPase mRNA response
      to interval exercise of increased alpha- but not beta-mRNA was largely preserved
      posttrain, suggesting a functional role of alpha mRNA upregulation.

PMID- 17446413
TI  - Effect of acute hyperlipidemia on autonomic and cardiovascular control in humans.
AB  - Blood lipids may detrimentally affect autonomic and circulatory control. We
      tested the hypotheses that acute elevations in free fatty acids and triglycerides
      (acute hyperlipidemia) impair baroreflex control of cardiac period [cardiovagal
      baroreflex sensitivity (BRS)] and muscle sympathetic nerve activity (MSNA:
      sympathetic BRS), increase MSNA at rest, and augment physiological responses to
      exercise. Eighteen young adults were examined in this randomized, double-blinded,
      and placebo-controlled study. BRS was determined using the modified Oxford
      technique before (pre) and 60 min (post) after initiating infusion of Intralipid
      (0.8 ml x m(-2) x min(-1)) and heparin (1,000 U/h) (experimental; n = 12) to
      induce acute hyperlipidemia, or saline (0.8 ml x m(-2) x min(-1)) and heparin
      (1,000 U/h) (control; n = 6). Responses to isometric handgrip to fatigue (IHG)
      were also determined. Blood pressure increased more (P < 0.05) in experimental
      than control subjects during the infusion. MSNA at rest (14 +/- 2 vs. 11 +/- 1
      bursts/min), cardiovagal (19.8 +/- 1.8 vs. 19.1 +/- 2.4 ms/mmHg pre and post,
      respectively) and sympathetic BRS (-5.5 +/- 0.6 vs. -5.2 +/- 0.4 au x beat(-1) x
      mmHg(-1)), and the neural and cardiovascular responses to IHG were unchanged by
      acute hyperlipidemia (pre vs. post) in experimental subjects. Similarly, MSNA at
      rest (10 +/- 2 vs. 12 +/- 2 bursts/min), cardiovagal (22.1 +/- 4.0 vs. 21.0 +/-
      4.6 ms/mmHg) and sympathetic BRS (-5.8 +/- 0.5 vs. -5.5 +/- 0.5 au x beat(-1) x
      mmHg(-1)), and the neural and cardiovascular responses to IHG were unchanged by
      the infusion in control subjects. These data do not provide experimental support
      for the concept that acute hyperlipidemia impairs reflex cardiovagal or
      sympathetic regulation in humans.

PMID- 17446414
TI  - Autonomic cardiovascular and respiratory control during prolonged spaceflights
      aboard the International Space Station.
AB  - Impaired autonomic control represents a cardiovascular risk factor during long
      term spaceflight. Little has been reported on blood pressure (BP), heart rate
      (HR), and heart rate variability (HRV) during and after prolonged spaceflight. We
      tested the hypothesis that cardiovascular control remains stable during prolonged
      spaceflight. Electrocardiography, photoplethysmography, and respiratory frequency
      (RF) were assessed in eight male cosmonauts (age 41-50 yr, body-mass index of 22
      28 kg/m2) during long-term missions (flight lengths of 162-196 days). Recordings
      were made 60 and 30 days before the flight, every 4 wk during flight, and on days
      3 and 6 postflight during spontaneous and controlled respiration. Orthostatic
      testing was performed pre- and postflight. RF and BP decreased during spaceflight
      (P < 0.05). Mean HR and HRV in the low- and high-frequency bands did not change
      during spaceflight. However, the individual responses were different and
      correlated with preflight values. Pulse-wave transit time decreased during
      spaceflight (P < 0.05). HRV reached during controlled respiration (6 breaths/min)
      decreased in six and increased in one cosmonaut during flight. The most
      pronounced changes in HR, BP, and HRV occurred after landing. The decreases in BP
      and RF combined with stable HR and HRV during flight suggest functional
      adaptation rather than pathological changes. Pulse-wave transit time shortening
      in our study is surprising and may reflect cardiac output redistribution in
      space. The decrease in HRV during controlled respiration (6 breaths/min)
      indicates reduced parasympathetic reserve, which may contribute to postflight
      disturbances.

PMID- 17446415
TI  - Effects of extracellular HCO3(-) on fatigue, pHi, and K+ efflux in rat skeletal
      muscles.
AB  - Elevated plasma HCO(3)(-) can improve exercise endurance in humans. This effect
      has been related to attenuation of the work-induced reduction in muscle pH, which
      is suggested to improve performance via at least two mechanisms: 1) less
      inhibition of muscle enzymes and 2) reduced opening of muscle K(ATP) channels
      with less ensuing reduction in excitability. Aiming at determining whether the
      ergogenic effect of HCO(3)(-) is related to effects on muscles, we examined the
      effect of elevating extracellular HCO(3)(-) from 25 to 40 mM (pH from 7.4 to 7.6)
      on fatigue, intracellular pH (pH(i)), and K(+) efflux in isolated rat skeletal
      muscles contracting isometrically. Fatigue induced by 30-Hz stimulation at 30 and
      37 degrees C was similar between soleus muscles incubated in high and normal
      HCO(3)(-) concentrations. In extensor digitorum longus muscles stimulated at 60
      Hz, elevated HCO(3)(-) did not affect fatigue at 30 degrees C. In soleus muscles,
      30-Hz stimulation induced a approximately 0.2 unit reduction in pH(i), as
      determined by using the pH-sensitive probe 2',7'-bis(2-carboxyethyl)-5(6)
      carboxyfluorescein. This reduction in pH(i) was not affected by elevated HCO(3)(
      ). Estimation of K(+) efflux using (86)Rb(+) showed that elevated HCO(3)(-) did
      not affect K(+) efflux at rest or during contractions. Similarly, other
      modifications of the intra- and extracellular pH had little effect on K(+) efflux
      during contraction. In conclusion, elevated extracellular HCO(3)(-) had no
      significant effect on muscle fatigue, pH(i), and K(+) efflux. These findings
      indicate that alternative mechanisms must be considered for the ergogenic effect
      of HCO(3)(-) observed in integral exercise studies.

PMID- 17446418
TI  - Depressive symptoms, risk of stroke and the stress response.

PMID- 17446419
TI  - Central paroxysmal positional vertigo: isolated dizziness caused by small
      cerebellar hemorrhage.

PMID- 17446420
TI  - Arterial baroreflex: a novel target for preventing stroke in rat hypertension.
AB  - BACKGROUND AND PURPOSE: Arterial baroreflex is one of the most important
      mechanisms in the regulation of cardiovascular activities. Arterial baroreflex
      function can be expressed as baroreflex sensitivity (BRS). The present study was
      designed to test 2 hypotheses: (1) BRS is a new independent predictor for the
      incidence of stroke in hypertension, and (2) restoration of BRS can prevent
      stroke in hypertension. METHODS: First, 82 stroke-prone spontaneously
      hypertensive rats (SHR-SP) aged 28 to 30 weeks were used. After measuring blood
      pressure and BRS, the survival time was observed. Second, 12 SHR-SP aged 8 months
      were used. Blood pressure and BRS were determined separately before and after
      intragastric administration of ketanserin (0.3 and 3.0 mg/kg). Third, SHR-SP aged
      5 months were treated with ketanserin for 12 weeks (0.3 mg and 3.0 mg/kg per
      day). At the end of the treatment, blood pressure and BRS were determined and the
      end-organ damage was evaluated. Last, SHR-SP aged 3 months were treated with
      ketanserin (0.3 and 3.0 mg/kg per day) for life and the survival time was
      recorded. RESULTS: Stroke was significantly delayed in rats with high BRS than
      those with low BRS (time to 50% death was 1.47-fold longer than low BRS group;
      P<0.01). Ketanserin of 3.0 mg/kg per day decreased blood pressure and enhanced
      BRS, whereas 0.3 mg/kg per day only enhanced the BRS. Fatal stroke incidences
      were markedly reduced by treatment with both doses (P<0.0001 versus control
      group). CONCLUSIONS: The present study provides evidence that BRS is an
      independent predictor for stroke in hypertension. Restoration of BRS may be a new
      strategy for the prevention of stroke.

PMID- 17446421
TI  - Validation of an acute ischemic stroke model: does diffusion-weighted imaging
      lesion volume offer a clinically significant improvement in prediction of
      outcome?
AB  - BACKGROUND AND PURPOSE: Prediction models for ischemic stroke outcome have the
      potential to contribute prognostic information in the clinical and/or research
      setting. The importance of diffusion-weighted magnetic resonance imaging (DWI) in
      the prediction of clinical outcome, however, is unclear. The purpose of this
      study was to combine acute clinical data and DWI lesion volume for ischemic
      stroke patients to determine whether DWI improves the prediction of clinical
      outcome. METHODS: Patients (N=382) with baseline DWI data from the Glycine
      Antagonist In Neuroprotection and citicoline (010 and 018) trials were used to
      develop the prediction models by multivariable logistic regression. Data from
      prospectively collected patients (N=266) from the Acute Stroke Accurate
      Prediction Study were used to externally validate the model equations. The models
      predicted either full recovery or nursing home-level disability/death, as defined
      by the National Institutes of Health Stroke Scale, Barthel Index, or modified
      Rankin Scale. RESULTS: The full-recovery models with DWI lesion volume had areas
      under the receiver operating characteristic curves (AUCs) of 0.799 to 0.821, and
      those without DWI lesion volume had AUCs of 0.758 to 0.798. The nursing home
      level disability/death models with DWI had AUCs of 0.832 to 0.882, and those
      without DWI had AUCs of 0.827 to 0.867. All models had mean absolute errors < or
      =0.4 for calibration. CONCLUSIONS: All 12 models had excellent discrimination and
      calibration, with 8 of 12 meeting prespecified performance criteria (AUC > or
      =0.8, mean absolute error < or =0.4). Although DWI lesion volume significantly
      increased model explanatory power, the magnitude of increase was not large enough
      to be clinically important.

PMID- 17446422
TI  - Adipophilin expression is increased in symptomatic carotid atherosclerosis:
      correlation with red blood cells and cholesterol crystals.
AB  - BACKGROUND AND PURPOSE: Adipophilin is an adipose differentiation-related protein
      expressed in lipid-containing cells. Using DNA microarray analysis, we previously
      found the adipophilin gene (ADFP) to be overexpressed in symptomatic carotid
      plaques (CP). This led us to further examine the role of adipophilin in carotid
      atherosclerosis relative to symptom status. METHODS: Ninety-eight high-grade
      (>70%) CPs were obtained in carotid endarterectomy. The relative expression of
      ADFP mRNA was measured by quantitative real-time RT-PCR, and the relative amount
      of adipophilin protein was quantified with Western blotting. Detailed
      topographical correlations with extravasated red blood cells and extracellular
      cholesterol crystals were obtained by means of immunohistochemistry. RESULTS: The
      relative expression of ADFP mRNA was increased in symptomatic compared with
      asymptomatic CPs at both the mRNA level (1.82+/-0.19[SE] versus 1.25+/-0.15,
      P=0.012) and the protein level (1.04+/-0.23 versus 0.46+/-0.14, P=0.043).
      Adipophilin colocalized with macrophage foam cells, extravasated red blood cells
      (P<0.0001), and cholesterol crystals (P<0.0001), and its expression associated
      with macroscopic ulceration of CP (P<0.0001). CONCLUSIONS: Intraplaque
      hemorrhages may contribute to intracellular lipid accumulation and consequent
      adipophilin expression. Because adipophilin blocks cholesterol efflux from lipid
      laden cells, they may die and develop a necrotic lipid core, thereby
      destabilizing the plaque.

PMID- 17446423
TI  - Nitric oxide synthase isoforms undertake unique roles during excitotoxicity.
AB  - BACKGROUND AND PURPOSE: Excitotoxicity is a component of many neurodegenerative
      diseases. The signaling events that lead from excitotoxic injury to neuronal
      death remain incompletely defined. Pharmacological approaches have shown that
      nitric oxide production is critical for the progression of neurodegeneration
      after the initiation of excitotoxicity by the glutamate analog kainate. Although
      nitric oxide additionally triggers blood-brain barrier (BBB) breakdown, the
      breakdown does not in itself inevitably lead to neuronal cell death, because
      neuroprotective pharmacological means can be used subsequently to prevent the
      neural death. METHODS: In this study, we use a genetic approach to analyze the
      contribution of 3 nitric oxide synthase (NOS) isoforms, neuronal NOS, endothelial
      NOS, and inducible NOS, to neurodegeneration and BBB breakdown in this setting.
      RESULTS: We find that neuronal NOS is critical for the progression of kainate
      stimulated neurodegeneration, whereas endothelial NOS is required only for BBB
      breakdown. Inducible NOS is not required for either event. CONCLUSIONS: The
      observation that endothelial NOS-deficient mice undergo excitotoxic
      neurodegeneration in the absence of BBB breakdown unlinks the two processes.
      These findings suggest that it may be possible to achieve full amelioration of
      excitotoxic-triggered neurodegeneration through developing isoform-specific
      inhibitors solely for neuronal NOS.

PMID- 17446424
TI  - Brain atrophy is related to lacunar lesions and tissue microstructural changes in
      CADASIL.
AB  - BACKGROUND AND PURPOSE: Cerebral atrophy has been recently recognized as a key
      marker of disease progression in cerebral autosomal-dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL). The contribution of
      subcortical cerebral lesions in this process remains undetermined. The aim of
      this study was to investigate the relationships between cerebral volume and
      different types of subcortical MRI lesions in CADASIL. METHODS: Demographic,
      clinical, and laboratory data from 147 patients with CADASIL recruited from a
      prospective cohort study were analyzed. Validated methods were used to determine
      the ratio of brain volume to intracranial cavity volume (brain parenchymal
      fraction [BPF]), volume of white matter hyperintensities, volume of lacunar
      lesions, number of cerebral microhemorrhages, and mean apparent diffusion
      coefficient. Associations between BPF, clinical scales, and the different
      subcortical MRI markers were tested. RESULTS: BPF obtained in 129 patients was
      significantly associated with the Mattis dementia rating scale (P<0.0001), Mini
      Mental State Examination (P=0.002), and modified Rankin scale (P<0.0001) after
      adjustment for age and sex. Multiple linear regression modeling showed that BPF
      was independently associated with mean apparent diffusion coefficient (P<0.0001),
      volume of lacunar lesions (P=0.004), and age (P<0.0001), accounting for 46% of
      the observed variance in BPF but not with volume of white matter hyperintensities
      or number of microhemorrhages. CONCLUSIONS: In association with age, mean
      apparent diffusion coefficient and volume of lacunar lesions are strong and
      independent MRI predictors of BPF, a key marker of cognitive and motor disability
      in CADASIL. These results suggest brain atrophy is related to remote and/or
      diffuse consequences of both lacunar lesions and widespread microstructural
      alterations within the brain outside lacunar lesions.

PMID- 17446425
TI  - Impairment of cerebral perfusion and infarct patterns attributable to vasospasm
      after aneurysmal subarachnoid hemorrhage: a prospective MRI and DSA study.
AB  - BACKGROUND AND PURPOSE: The objective of this study was to investigate
      disturbance of perfusion and infarct patterns attributable to cerebral vasospasm
      (CVS) after subarachnoid hemorrhage (SAH). METHODS: One hundred seventeen
      patients with aneurysmal SAH specifically selected at high risk for CVS were
      enrolled in this prospective study. One hundred twelve patients underwent
      surgical (n=63) or endovascular (n=59) therapy. For assessment of CVS, relative
      diameter changes of proximal and distal vessel segments on follow-up angiography
      at day 7+/-3 after SAH were analyzed in relation to baseline measurements, and
      cerebral circulation times were measured. Postprocedure MRI was undertaken
      selectively at four time points: within 3 days, between days 4 and 6, day 7 to
      14, and day 15 to 28 from onset of SAH, including perfusion- and diffusion
      weighted images. Procedure-related lesions were excluded and CVS-associated
      infarct patterns analyzed. RESULTS: Occurrence of angiographic CVS was as high as
      87.5% between days 7 and 14 and 52.5% showed new infarcts. Eighty-one percent of
      the infarcts were related to severe CVS (vascular narrowing >66%) and significant
      (P<0.001) cerebral circulation times prolongation of 8.47+/-2.25 seconds (time-to
      peak delay on perfusion-weighted image: 6.52+/-4.75 seconds), 16% were associated
      with moderate CVS (34% to 66% vascular narrowing; cerebral circulation times
      prolongation: 4.72+/-0.66 seconds). Besides territorial (47%), lacunar (20%), and
      watershed infarcts (26%), in 7%, band-like cortical lesions developed without
      evidence for severe CVS. CONCLUSIONS: CVS after SAH may involve the complete
      arterial system from the circle of Willis up to the distal vessel segments.
      Depending on the variable types of collateral flow, location of affected vessels
      segments as well as the degree of CVS may induce different infarct patterns.

PMID- 17446426
TI  - Usefulness of cardiovascular investigations in stroke management: clinical
      relevance and economic implications.
AB  - BACKGROUND AND PURPOSE: There are no prospective randomized studies assessing the
      clinical relevance of routine cardiovascular investigations in stroke patients.
      The objective of this study was to evaluate the utilization, relevance, and
      economics of cardiovascular investigations in an ambulatory stroke clinic.
      METHODS: The outcome of cardiovascular investigations in 200 patients with
      stroke/transient ischemic attack diagnosed in a stroke prevention clinic was
      assessed. Transthoracic echocardiography (TTE) was assessed for detection of
      thrombus or mass, poor left ventricle function, and other structural
      abnormalities. ECG and Holter monitor were felt to be relevant if they showed
      atrial fibrillation/flutter. Investigations were deemed to be clinically
      pertinent if they brought about a shift treatment paradigm. RESULTS: TTE and
      Holter were performed in >70% of cases and accounted for approximately 94% of
      total cardiovascular cost. Relevant TTE findings were identified in 6 (4%)
      patients, which did not alter antithrombotic therapy. Only 2 new cases of atrial
      fibrillation were identified by both ECG and Holter. CONCLUSIONS: TTE and Holter
      appear to be costly low-yield procedures in this clinical setting. Prospective
      analyses may help to provide cost effective criteria for selection of appropriate
      cardiovascular studies in stroke management.

PMID- 17446427
TI  - High-sensitivity C-reactive protein is not associated with carotid intima-media
      progression: the carotid atherosclerosis progression study.
AB  - BACKGROUND AND PURPOSE: It is unclear whether elevated serum C-reactive protein
      (CRP) is causal to the initiation and progression of atherosclerosis. We
      undertook a prospective longitudinal cohort study to address this question.
      METHODS: In a population-based sample of 3122 subjects, we measured carotid
      intima media thickness (IMT) at baseline and after 3 years and surveyed clinical
      events. Associations between baseline high-sensitivity CRP (hs-CRP) and baseline
      IMT, and IMT progression were determined before and after controlling for
      vascular risk factors. The relationship between baseline IMT and clinical events
      during follow up was determined. RESULTS: All vascular risk factors were
      significantly associated with hs-CRP (P<0.001). Hs-CRP was significantly
      associated with baseline IMT in all carotid segments (P<0.001), but this
      association was no longer significant after controlling for age, gender, and
      cardiovascular risk factors. Hs-CRP was not related to individual IMT
      progression. Interactions between hs-CRP and body mass index, HbA1c, or blood
      pressure showed no association with IMT progression. Baseline hs-CRP was related
      to the risk of clinical events (myocardial infarction or stroke or death, hazard
      ratio of 1.22 per mg/L hs-CRP increase, 95% CI: 1.07 to 1.39, P=0.004, adjusted
      for age and gender), but this association was not significant after controlling
      for age, gender, and cardiovascular risk factors (1.59, 95% CI: 0.96 to 2.64,
      P=0.072). CONCLUSIONS: Our results suggest that hs-CRP is not an independent
      causal factor for the initiation and progression of early atherosclerotic changes
      of the carotid arteries. Univariate associations between hs-CRP and IMT were
      largely explained by confounding by age, gender, and cardiovascular risk factors.

PMID- 17446428
TI  - Cardiac surgery for infective endocarditis, complicated by septic cardioembolic
      stroke.

PMID- 17446429
TI  - Predictive variables for mortality after acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Stroke is a major healthcare issue worldwide with an
      incidence comparable to coronary events, highlighting the importance of
      understanding risk factors for stroke and subsequent mortality. METHODS: In the
      present study, we determined long-term (all-cause) mortality in 545 patients with
      ischemic stroke compared with a cohort of 330 age-matched healthy control
      subjects followed up for a median of 7.4 years. We assessed the effect of
      selected demographic, clinical, biochemical, hematologic, and hemostatic factors
      on mortality in patients with ischemic stroke. Stroke subtype was classified
      according to the Oxfordshire Community Stroke Project criteria. Patients who died
      30 days or less after the acute event (n=32) were excluded from analyses because
      this outcome is considered to be directly attributable to the acute event.
      RESULTS: Patients with ischemic stroke were at more than 3-fold increased risk of
      death compared with the age-matched control cohort. In multivariate analyses,
      age, stroke subtype, atrial fibrillation, and previous stroke/transient ischemic
      attack were predictive of mortality in patients with ischemic stroke. Albumin and
      creatinine and the hemostatic factors von Willebrand factor and beta
      thromboglobulin were also predictive of mortality in patients with ischemic
      stroke after accounting for demographic and clinical variables. CONCLUSIONS: The
      results indicate that subjects with acute ischemic stroke are at increased risk
      of all-cause mortality. Advancing age, large-vessel stroke, atrial fibrillation,
      and previous stroke/transient ischemic attack predict mortality; and analysis of
      albumin, creatinine, von Willebrand factor, and beta-thromboglobulin will aid in
      the identification of patients at increased risk of death after stroke.

PMID- 17446430
TI  - The Virtual International Stroke Trials Archive.
AB  - BACKGROUND AND PURPOSE: Stroke has global importance and it causes an increasing
      amount of human suffering and economic burden, but its management is far from
      optimal. The unsuccessful outcome of several research programs highlights the
      need for reliable data on which to plan future clinical trials. The Virtual
      International Stroke Trials Archive aims to aid the planning of clinical trials
      by collating and providing access to a rich resource of patient data to perform
      exploratory analyses. METHODS: Data were contributed by the principal
      investigators of numerous trials from the past 16 years. These data have been
      centrally collated and are available for anonymized analysis and hypothesis
      testing. RESULTS: Currently, the Virtual International Stroke Trials Archive
      contains 21 trials. There are data on >15,000 patients with both ischemic and
      hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 69+/
      12 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale,
      National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin
      Scale. Medical history and onset-to-treatment time are readily available, and
      computed tomography lesion data are available for selected trials. CONCLUSIONS:
      This resource has the potential to influence clinical trial design and
      implementation through data analyses that inform planning.

PMID- 17446431
TI  - Association between disability measures and healthcare costs after initial
      treatment for acute stroke.
AB  - BACKGROUND AND PURPOSE: The distribution of 3-month modified Rankin scale (mRS)
      scores has been used as an outcome measure in acute stroke trials. We
      hypothesized that hospitalization and institutional care home stays within the
      first 90 days after stroke should be closely related to 90-day mRS, that each
      higher mRS category will reflect incremental cost, and that resource use may be
      less clearly linked to the National Institutes of Health Stroke Scale (NIHSS) or
      Barthel index. METHODS: We examined resource use data from the GAIN International
      trial comparing 90-day mRS with total length of stay in hospital or other
      institutions during the first 90 days. We repeated analyses using NIHSS and
      Barthel index scores. Relationships were examined by analysis of variance (ANOVA)
      with Bonferroni contrasts of adjacent score categories. Estimated costs were
      based on published Scottish figures. RESULTS: We had full data from 1717
      patients. Length of stay was strongly associated with final mRS (P<0.0001). Each
      mRS increment from 0 to 1-2 to 3-4 was significant (mean length of stay: 17, 25,
      44, 58, 79 days; P<0.0005). Ninety-five percent confidence limits for estimated
      costs ( pound) rose incrementally: 2493 to 3412, 3369 to 4479, 5784 to 7008, 7300
      to 8512, 10 095 to 11 141, 11 772 to 13 560, and 2623 to 3321 for mRS 0 to 5 and
      dead, respectively. Weaker relationships existed with Barthel and NIHSS.
      CONCLUSIONS: Each mRS category reflects different average length of hospital and
      institutional stay. Associated costs are meaningfully different across the full
      range of mRS outcomes. Analysis of the full distribution of mRS scores is
      appropriate for interpretation of treatment effects after acute stroke and more
      informative than Barthel or NIHSS end points.

PMID- 17446432
TI  - Low density lipoprotein undergoes oxidation within lysosomes in cells.
AB  - The oxidized low density lipoprotein (LDL) hypothesis of atherosclerosis proposes
      that LDL undergoes oxidation in the interstitial fluid of the arterial wall. We
      have shown that aggregated (vortexed) nonoxidized LDL was taken up by J774 mouse
      macrophages and human monocyte-derived macrophages and oxidized intracellularly,
      as assessed by the microscopic detection of ceroid, an advanced lipid oxidation
      product. Confocal microscopy showed that the ceroid was located in the lysosomes.
      To confirm these findings, J774 macrophages were incubated with acetylated LDL,
      which is internalized rapidly to lysosomes, and then incubated (chase incubation)
      in the absence of any LDL. The intracellular levels of oxysterols, measured by
      HPLC, increased during the chase incubation period, showing that LDL must have
      been oxidized inside the cells. Furthermore, we found that this oxidative
      modification was inhibited by lipid-soluble antioxidants, an iron chelator taken
      up by fluid-phase pinocytosis and the lysosomotropic drug chloroquine, which
      increases the pH of lysosomes. The results indicate that LDL oxidation can occur
      intracellularly, most probably within lysosomes.

PMID- 17446433
TI  - Formation of extracellular matrix-digesting invadopodia by primary aortic smooth
      muscle cells.
AB  - Invasion of the subendothelial space by vascular smooth muscle cells (VSMCs)
      contributes to the development and progression of diverse cardiovascular
      diseases. In this report we show that the expression of activated versions of
      Src, Cdc42 and Rac1, or a kinase-dead but open form of the p21-activated kinase
      (PAK1), induces primary rat aorta VSMCs to form extracellular matrix-degrading
      actin-rich protrusions that are morphologically similar to the invadopodia formed
      by highly invasive tumor cells. The matrix-degrading structures are enriched in
      known markers for invadopodia, including cortactin and tyrosine-phosphorylated
      cortactin and contain the matrix metalloproteinases MMP-9 and MT1-MMP and the
      urokinase plasminogen activator receptor (uPAR). In contrast to other cell types,
      invadopodia formation in VSMCs is only weakly supported by the phorbol ester
      PBDu. Invadopodia formation by Src was dependent on Cdc42, Rac, and ERK, but not
      on p38 MAPK. Invadopodia formation induced by kinase-dead PAK1 required Src and
      ERK activity and a direct interaction with the exchange factor PIX. VSMCs
      embedded in a three-dimensional collagen matrix formed actin- and cortactin-rich
      extensions that penetrated through holes in the matrix, suggesting that
      invadopodia-like structures are formed in a three-dimensional environment.

PMID- 17446434
TI  - C-reactive protein downregulates endothelial NO synthase and attenuates
      reendothelialization in vivo in mice.
AB  - C-reactive protein (CRP) is an acute-phase reactant that is positively associated
      with cardiovascular disease risk and endothelial dysfunction. In cell culture,
      CRP decreases the expression of endothelial NO synthase (eNOS), which regulates
      diverse endothelial cell (EC) functions including migration. To determine whether
      CRP alters EC gene expression and phenotype in vivo, we studied CF1 transgenic
      mice expressing rabbit CRP (CF1-CRP) regulated by the phosphoenolpyruvate
      carboxykinase promoter such that levels could be altered by changing carbohydrate
      intake. Compared with CF1 controls with CRP of <1 microg/mL, carotid artery
      reendothelialization after perivascular electric injury was blunted in CF1-CRP
      mice, with CRP levels as low as 9 microg/mL. eNOS mRNA and enzyme abundance in
      carotid arteries was also blunted by CRP at 9 microg/mL in vivo, and ex vivo
      studies of isolated arteries showed that this occurs via direct action on the
      endothelium. The impaired reendothelialization with CRP was mimicked by NOS
      antagonism in CF1 mice; conversely, in cultured ECs CRP attenuation of migration
      was prevented by exogenous NO. Studies of EC transfected with human eNOS 5'
      flanking sequence fused to luciferase indicated that CRP decreases eNOS gene
      transcription. Both mutagenesis and electrophoretic mobility shift assays further
      revealed that CRP-responsive elements reside within the first 79 bp of the eNOS
      promoter. Thus, CRP downregulates eNOS and attenuates reendothelialization in
      vivo in mice, and this action of CRP on eNOS is mediated at the level of gene
      transcription.

PMID- 17446435
TI  - The troponin C G159D mutation blunts myofilament desensitization induced by
      troponin I Ser23/24 phosphorylation.
AB  - Striated muscle contraction is regulated by the binding of Ca(2+) to the N
      terminal regulatory lobe of the cardiac troponin C (cTnC) subunit in the troponin
      complex. In the heart, beta-adrenergic stimulation induces protein kinase A
      phosphorylation of cardiac troponin I (cTnI) at Ser23/24 to alter the interaction
      of cTnI with cTnC in the troponin complex and is critical to the regulation of
      cardiac contractility. We investigated the effect of the dilated cardiomyopathy
      linked cTnC Gly159 to Asp (cTnC-G159D) mutation on the development of Ca(2+)
      dependent tension and ATPase rate in whole troponin-exchanged skinned rat
      trabeculae. Even though this mutation is located in the C-terminal lobe of cTnC,
      the G159D mutation was demonstrated to depress ATPase activation and filament
      sliding in vitro. The effects of this mutation within the cardiac myofilament are
      unknown. Our results demonstrate that the cTnC-G159D mutation by itself does not
      alter the myofilament response to Ca(2+) in the cardiac muscle lattice. However,
      in the presence of cTnI phosphorylated at Ser23/24, which reduced Ca(2+)
      sensitivity and enhanced cross-bridge cycling in controls, cTnC-G159D
      specifically blunted the phosphorylation induced decrease in Ca(2+)-sensitive
      tension development without altering cross-bridge cycling. Measurements in
      purified troponin confirmed that this cTnC-G159D blunting of myofilament
      desensitization results from altered Ca(2+)-binding to cTnC. Our results provide
      novel evidence that modification of the cTnC-cTnI interaction has distinct
      effects on troponin Ca(2+)-binding and cross-bridge kinetics to suggest a novel
      role for thin filament mutations in the modulation of myofilament function
      through beta-adrenergic signaling as well as the development of cardiomyopathy.

PMID- 17446436
TI  - Sirt1 regulates aging and resistance to oxidative stress in the heart.
AB  - Silent information regulator (Sir)2, a class III histone deacetylase, mediates
      lifespan extension in model organisms and prevents apoptosis in mammalian cells.
      However, beneficial functions of Sir2 remain to be shown in mammals in vivo at
      the organ level, such as in the heart. We addressed this issue by using
      transgenic mice with heart-specific overexpression of Sirt1, a mammalian homolog
      of Sir2. Sirt1 was significantly upregulated (4- to 8-fold) in response to
      pressure overload and oxidative stress in nontransgenic adult mouse hearts. Low
      (2.5-fold) to moderate (7.5-fold) overexpression of Sirt1 in transgenic mouse
      hearts attenuated age-dependent increases in cardiac hypertrophy,
      apoptosis/fibrosis, cardiac dysfunction, and expression of senescence markers. In
      contrast, a high level (12.5-fold) of Sirt1 increased apoptosis and hypertrophy
      and decreased cardiac function, thereby stimulating the development of
      cardiomyopathy. Moderate overexpression of Sirt1 protected the heart from
      oxidative stress induced by paraquat, with increased expression of antioxidants,
      such as catalase, through forkhead box O (FoxO)-dependent mechanisms, whereas
      high levels of Sirt1 increased oxidative stress in the heart at baseline. Thus,
      mild to moderate expression of Sirt1 retards aging of the heart, whereas a high
      dose of Sirt1 induces cardiomyopathy. Furthermore, although high levels of Sirt1
      increase oxidative stress, moderate expression of Sirt1 induces resistance to
      oxidative stress and apoptosis. These results suggest that Sirt1 could retard
      aging and confer stress resistance to the heart in vivo, but these beneficial
      effects can be observed only at low to moderate doses (up to 7.5-fold) of Sirt1.

PMID- 17446437
TI  - Association of ATP1A1 and dear single-nucleotide polymorphism haplotypes with
      essential hypertension: sex-specific and haplotype-specific effects.
AB  - Essential hypertension remains a major risk factor for cardiovascular and
      cerebrovascular diseases. As a complex multifactorial disease, elucidation of
      susceptibility loci remains elusive. ATP1A1 and Dear are candidate genes for 2
      closely linked rat chromosome-2 blood pressure quantitative trait loci. Because
      corresponding human syntenic regions are on different chromosomes, investigation
      of ATP1A1 (chromosome [chr]-1p21) and Dear (chr-4q31.3) facilitates genetic
      analyses of each blood pressure quantitative trait locus in human hypertension.
      Here we report the association of human ATP1A1 (P<0.000005) and Dear (P<0.03)
      with hypertension in a relatively isolated, case/control hypertension cohort from
      northern Sardinia by single-nucleotide polymorphism haplotype analysis. Sex
      specific haplotype analyses detected stronger association of both loci with
      hypertension in males than in females. Haplotype trend-regression analyses
      support ATP1A1 and Dear as independent susceptibility loci and reveal haplotype
      specific association with hypertension and normotension, thus delineating
      haplotype-specific subsets of hypertension. Although investigation in other
      cohorts needs to be performed to determine genetic effects in other populations,
      haplotype subtyping already allows systematic stratification of susceptibility
      and, hence, clinical heterogeneity, a prerequisite for unraveling the polygenic
      etiology and polygene-environment interactions in essential hypertension. As
      hypertension susceptibility genes, coexpression of ATP1A1 and Dear in both renal
      tubular cells and vascular endothelium suggest a cellular pathogenic scaffold for
      polygenic mechanisms of hypertension, as well as the hypothesis that ATP1A1
      and/or Dear could contribute to the known renal and vascular endothelial
      dysfunction associated with essential (polygenic) hypertension.

PMID- 17446438
TI  - Loss-of-function deletion of the steroid receptor coactivator-1 gene in mice
      reduces estrogen effect on the vascular injury response.
AB  - OBJECTIVE: The steroid receptor coactivator-1 (SRC-1) is a transcriptional
      coactivator for nuclear receptors including estrogen receptor (ER). SRC-1 can
      interact with ER in an estrogen binding-dependent manner to potentiate the
      transcriptional activity of ER. Previous studies showed that SRC-1 was required
      for the full function of ER in cultured cells and in the reproductive system. In
      this study, we have tested the hypothesis that SRC-1 is required for the
      inhibition of neointima formation by estrogen in a vascular wall. METHODS AND
      RESULTS: The expression of SRC-1 protein in the vascular wall was examined by
      immunoblotting and immunohistochemistry. Wild-type and SRC-1 null mice were
      ovariectomized, and then unilateral ligation of the carotid artery was performed
      to induce neointima growth in these mice. Mice were treated with placebo or
      estrogen. Neointima growth near the ligation site was examined and quantitatively
      analyzed. These experiments demonstrated that SRC-1 was expressed in the
      endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and neointima
      cells. The neointima growth induced by the ligation of common carotid artery was
      almost completely inhibited by estrogen in wild-type mice, but was only partially
      inhibited in SRC-1-null mice. Further analysis revealed that the blunted
      inhibition of neointima formation by estrogen was attributed to a less inhibition
      of neointimal cell proliferation. CONCLUSIONS: SRC-1 is expressed in ECs, VSMCs,
      and neointima cells. SRC-1 expression in these cells facilitates estrogen/ER
      mediated vasoprotection through the inhibition of neointima formation after a
      vascular injury.

PMID- 17446439
TI  - Repetition of ischemic preconditioning augments endothelium-dependent
      vasodilation in humans: role of endothelium-derived nitric oxide and endothelial
      progenitor cells.
AB  - BACKGROUND: Several studies have shown that both early and late effects of
      ischemic preconditioning (IPC) protect against myocardial injury after ischemic
      reperfusion. METHODS AND RESULTS: The purpose of this study was to evaluate the
      late effects of IPC on endothelial function in humans. Late phase of IPC was
      induced by upper limb ischemia (cuff inflation of over 200 mm Hg for 5 minutes) 6
      times a day for 1 month. We evaluated forearm blood flow (FBF) responses to
      acetylcholine (ACh) and to sodium nitroprusside (SNP) before and after IPC
      stimulus in 30 young healthy men. FBF was measured using a strain-gauge
      plethysmograph. The IPC stimulus significantly increased plasma concentration of
      vascular endothelial growth factor (VEGF), circulating level of endothelial
      progenitor cells (EPCs), and FBF responses to ACh, but these did not change in
      the control group. The FBF responses to SNP were similar before and after the IPC
      stimulus. Infusion of N(G)-monomethyl-L-arginine, a nitric oxide synthase
      inhibitor, completely eliminated the IPC stimulus-induced augmentation of FBF
      responses to ACh. In the contralateral arms of subjects that received the IPC
      stimulus, FBF responses to ACh did not change, but levels of VEGF and circulating
      EPCs increased. CONCLUSIONS: These findings suggest that repetition of late IPC
      stimulus augments endothelium-dependent vasodilation in humans through increases
      in nitric oxide production and number of EPCs under a local condition. Repetition
      of IPC stimulus may be a simple, safe, and feasible therapeutic technique for
      endothelial protection of peripheral vessels.

PMID- 17446440
TI  - Enhanced immune system activation and arterial inflammation accelerates
      atherosclerosis in lupus-prone mice.
AB  - OBJECTIVE: Premature atherosclerosis is a characteristic feature of systemic
      lupus erythematosus, a prototypic autoimmune disease. The principle cellular and
      molecular mechanisms which underlie such accelerated atherosclerosis are
      indeterminate. METHODS AND RESULTS: The pathophysiology of lupus-mediated
      atherogenesis was evaluated in a novel animal model involving transplantation of
      bone marrow cells from the lupus prone strain gld into Ldl-r(-/-) mice. Diet
      induced atherogenesis in lethally-irradiated Ldl-r(-/-) mice transplanted with
      gld bone marrow cells resulted in accelerated atherosclerosis (+65%) as compared
      with control mice transplanted with wild-type marrow cells. Enhanced
      atherogenesis was associated with enhanced activation of both B and T lymphocytes
      and with arterial inflammation involving endothelial cell activation, monocyte
      recruitment, and accumulation of apoptotic debris, macrophages, and CD4 T cells,
      but was independent of plasma lipid levels and renal function. CONCLUSIONS: Our
      data support the contention that despite the absence of both disturbed
      cholesterol homeostasis and renal dysfunction in autoimmune gld-->Ldl-r(-/-)
      mice, lupus disease induces enhanced activation of the immune system and acts
      locally on the vasculature to induce inflammation, together with accumulation of
      apoptotic debris, macrophages, and CD4 T cells, thereby accelerating plaque
      progression.

PMID- 17446442
TI  - Prevention of infective endocarditis: guidelines from the American Heart
      Association: a guideline from the American Heart Association Rheumatic Fever,
      Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease
      in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular
      Surgery and Anesthesia, and the Quality of Care and Outcomes Research
      Interdisciplinary Working Group.
AB  - BACKGROUND: The purpose of this statement is to update the recommendations by the
      American Heart Association (AHA) for the prevention of infective endocarditis
      that were last published in 1997. METHODS AND RESULTS: A writing group was
      appointed by the AHA for their expertise in prevention and treatment of infective
      endocarditis, with liaison members representing the American Dental Association,
      the Infectious Diseases Society of America, and the American Academy of
      Pediatrics. The writing group reviewed input from national and international
      experts on infective endocarditis. The recommendations in this document reflect
      analyses of relevant literature regarding procedure-related bacteremia and
      infective endocarditis, in vitro susceptibility data of the most common
      microorganisms that cause infective endocarditis, results of prophylactic studies
      in animal models of experimental endocarditis, and retrospective and prospective
      studies of prevention of infective endocarditis. MEDLINE database searches from
      1950 to 2006 were done for English-language papers using the following search
      terms: endocarditis, infective endocarditis, prophylaxis, prevention, antibiotic,
      antimicrobial, pathogens, organisms, dental, gastrointestinal, genitourinary,
      streptococcus, enterococcus, staphylococcus, respiratory, dental surgery,
      pathogenesis, vaccine, immunization, and bacteremia. The reference lists of the
      identified papers were also searched. We also searched the AHA online library.
      The American College of Cardiology/AHA classification of recommendations and
      levels of evidence for practice guidelines were used. The paper was subsequently
      reviewed by outside experts not affiliated with the writing group and by the AHA
      Science Advisory and Coordinating Committee. CONCLUSIONS: The major changes in
      the updated recommendations include the following: (1) The Committee concluded
      that only an extremely small number of cases of infective endocarditis might be
      prevented by antibiotic prophylaxis for dental procedures even if such
      prophylactic therapy were 100% effective. (2) Infective endocarditis prophylaxis
      for dental procedures is reasonable only for patients with underlying cardiac
      conditions associated with the highest risk of adverse outcome from infective
      endocarditis. (3) For patients with these underlying cardiac conditions,
      prophylaxis is reasonable for all dental procedures that involve manipulation of
      gingival tissue or the periapical region of teeth or perforation of the oral
      mucosa. (4) Prophylaxis is not recommended based solely on an increased lifetime
      risk of acquisition of infective endocarditis. (5) Administration of antibiotics
      solely to prevent endocarditis is not recommended for patients who undergo a
      genitourinary or gastrointestinal tract procedure. These changes are intended to
      define more clearly when infective endocarditis prophylaxis is or is not
      recommended and to provide more uniform and consistent global recommendations.

PMID- 17446441
TI  - Adenovirus-mediated expression of human paraoxonase 3 protects against the
      progression of atherosclerosis in apolipoprotein E-deficient mice.
AB  - OBJECTIVE: We have previously reported that human paraoxonase 3 (PON3) is an HDL
      associated protein capable of preventing LDL oxidation in vitro. The objective of
      the present study was to determine whether elevated levels of human PON3 in mice
      could protect against the progression of atherosclerosis in vivo. METHODS AND
      RESULTS: Twenty-six week-old apolipoprotein E-deficient mice were injected with
      3x10(11) particles of adenovirus expressing either GFP alone (AdGFP) or together
      with human PON3 (AdPON3). Three weeks after injection, lesion area was
      significantly lower in AdPON3-treated mice compared with AdGFP controls. Serum
      from AdPON3 mice contained significantly lower levels of lipid hydroperoxides and
      exhibited an enhanced potential to efflux cholesterol from cholesterol-loaded
      macrophages. In addition, LDL was less susceptible to oxidation, whereas HDL was
      more capable of protecting against LDL oxidation. Exogenous human PON3 was not
      detected in the serum or HDL and more surprisingly we demonstrate that endogenous
      mouse PON3 is not associated with HDL, suggesting that the antioxidant function
      of PON3 is at the cellular level in mice. CONCLUSIONS: This study demonstrates
      for the first time that PON3 enhances the antiatherogenic capacity of serum and
      protects against the progression of atherosclerosis in vivo.

PMID- 17446444
TI  - Historical note regarding the discovery of the Na/Ca exchanger and the PMCA.

PMID- 17446445
TI  - Regulation of the cardiac Na+/Ca2+ exchanger by calcineurin and protein kinase C.
AB  - Na+/Ca2+ exchanger (NCX) activity is markedly inhibited in hypertrophic neonatal
      rat cardiomyocytes subjected to chronic phenylephrine treatment. This inhibition
      is reversed partially and independently by acute inhibition of calcineurin and
      protein kinase C (PKC) activities. Similar NCX inhibition occurs in CCL39 cells
      expressing cloned wild-type NCX1, when they are infected with adenoviral vectors
      carrying activated calcineurin A and then treated acutely with phorbol myristoyl
      acetate or protein phosphatase-1 inhibitors. The data obtained with these cells
      suggest that calcineurin activity, PKCalpha-mediated NCX1 phosphorylation, and
      the central loop of NCX1 (possibly its beta1 repeat) are required for the
      observed NCX inhibition. We observe partial inhibition of NCX activity
      independent of NCX1 phosphorylation when CCL39 cells are infected with activated
      calcineurin A but not further treated with phorbol myristoyl acetate or
      phosphatase inhibitors. Calcineurin thus appears to downregulate NCX activity via
      two independent mechanisms, one involving NCX1 phosphorylation and the other not
      involving NCX1 phosphorylation. These data indicate the existence of a novel
      regulatory mechanism for NCX1 involving calcineurin and PKC, which may be
      important in cardiac pathology.

PMID- 17446446
TI  - New modes of exchanger regulation: physiological implications.
AB  - Exchange activity is regulated principally by cytosolic Na+, Ca2+, and PIP2.
      However, the properties of these modes of regulation that have emerged from
      excised patch studies appear to be poorly suited to regulating exchange activity
      on a beat-to-beat basis. Here we summarize recent findings from our lab
      indicating that (a) allosteric activation by Ca2+ exhibits hysteresis, (b)
      elevated concentrations of cytosolic Na+ induce a mode of activity that no longer
      requires regulatory Ca2+ activation, and (c) the requirement for PIP2 is reduced
      or eliminated after allosteric Ca2+ activation. Our results suggest that exchange
      activity in cardiac myocytes may be regulated by the time-integral of Ca2+
      transients occurring over multiple beats.

PMID- 17446447
TI  - Shedding light on the Na+/Ca2+ exchanger.
AB  - The Na+/Ca2+ exchanger (NCX) regulates cardiac contractility by adjusting the
      amount of Ca2+ inside myocytes. NCX accomplishes this by using the
      electrochemical gradient of Na+: during each cycle three Na+ ions enter the cell
      and one Ca2+ ion is extruded against its gradient. In addition to being
      transported, cytoplasmic Na+ and Ca2+ ions also regulate exchanger activity. The
      physiological relevance and molecular processes underlying ionic regulation
      remain unclear. Also unresolved are the events that regulate NCX trafficking to
      the membrane and its oligomeric state. This is essential information to interpret
      structure-function data. The full-length exchanger was fused to both CFP and YFP,
      creating active fluorescent exchangers used in FRET experiments to assess both
      conformational changes associated with ionic regulation and the oligomeric state
      of NCX. Electrophysiological characterization demonstrates that these constructs
      behave similarly to the wild-type (WT) exchanger. We have been able for the first
      time to monitor conformational changes of the exchanger Ca2+-binding site in
      vivo. These studies provide a better understanding of the molecular properties of
      the NCX.

PMID- 17446448
TI  - The regulation of the Na/Ca exchanger and plasmalemmal Ca2+ ATPase by other
      proteins.
AB  - Na/Ca exchanger (NCX) and plasma membrane Ca2+ ATPase are the Ca2+ efflux
      mechanisms known in mammalian cells. NCX is the main transporter to efflux
      intracellular Ca2+ in the heart. NCX protein contains nine putative transmembrane
      domains and a large intracellular loop joining two sets of the transmembrane
      domains. The intracellular loop regulates the activity of the NCX by interacting
      with other proteins and nonprotein factors, such as ions, PIP2. Several proteins
      that are associated with NCX have been identified recently. Similarly,
      plasmalemmal Ca2+ ATPase (PMCA) has 10 putative transmembrane domains, and the C
      terminal intracellular region inhibits transporter activity. There are several
      proteins associated with PMCA, and the roles of the associated proteins of PMCA
      vary from specific localization to involving PMCA in signal transduction.
      Elucidation of structural and functional roles played by these associated
      proteins of NCX and PMCA will provide opportunities to develop drugs of potential
      therapeutic value.

PMID- 17446449
TI  - Phosphorylation and other conundrums of Na/Ca exchanger, NCX1.
AB  - The Na+/Ca2+ exchanger (NCX) is an important Ca2+ transport mechanism in
      virtually all cells in the body. There are three genes that control the
      expression of NCX in mammals. There are at least 16 alternatively spliced
      isoforms of NCX1 that target muscle and nerve and other tissues. Here we briefly
      discuss three remarkable regulatory issues or "conundrums" that involve the most
      prevalently expressed gene, NCX1. (1) How is NCX1 regulated by phosphorylation?
      We suggest that the macromolecular complex of NCX1 plays a critical role in the
      regulation of NCX. The role of the macromolecular complex and evidence supporting
      its existence and functional importance is presented. (2) Can there be transport
      block of a single "mode" of NCX1 transport by drugs or therapeutic agents? The
      simple answer is "no." A brief explanation is provided. (3) How can NCX1 knockout
      mice live? The answer is "by other compensatory regulatory mechanisms." These
      conundrums highlight important features in NCX1 and lay the foundation for new
      experiments to elucidate function and regulation of NCX1 and provide a context
      for investigations that seek to understand novel therapeutic agents.

PMID- 17446450
TI  - Regulation of cardiac Na+/Ca2+ exchanger by phospholemman.
AB  - Phospholemman (PLM) is the first sequenced member of the FXYD family of
      regulators of ion transport. The mature protein has 72 amino acids and consists
      of an extracellular N terminus containing the signature FXYD motif, a single
      transmembrane (TM) domain, and a cytoplasmic C-terminal domain containing four
      potential sites for phosphorylation. PLM and other members of the FXYD family are
      known to regulate Na+-K+-ATPase. Using adenovirus-mediated gene transfer into
      adult rat cardiac myocytes, we showed that changes in contractility and
      intracellular Ca2+ homeostasis associated with PLM overexpression or
      downregulation are not consistent with the effects expected from inhibition of
      Na+-K+-ATPase by PLM. Additional studies with heterologous expression of PLM and
      cardiac Na+/Ca2+ exchanger 1 (NCX1) in HEK293 cells and cardiac myocytes isolated
      from PLM-deficient mice demonstrated by co-localization, co-immunoprecipitation,
      and electrophysiological and radioactive tracer uptake techniques that PLM
      associates with NCX1 in the sarcolemma and transverse tubules and that PLM
      inhibits NCX1, independent of its effects on Na+-K+-ATPase. Mutational analysis
      indicates that the cytoplasmic domain of PLM is required for its regulation of
      NCX1. In addition, experiments using phosphomimetic and phospho-deficient PLM
      mutants, as well as activators of protein kinases A and C, indicate that PLM
      phosphorylated at serine68 is the active form that inhibits NCX1. This is in
      sharp contrast to the finding that the unphosphorylated PLM form inhibits Na+-K+
      ATPase. We conclude that PLM regulates cardiac contractility by modulating the
      activities of NCX and Na+-K+-ATPase.

PMID- 17446451
TI  - The squid preparation as a general model for ionic and metabolic Na+/Ca2+
      exchange interactions: physiopathological implications.
AB  - We propose an integrated kinetic model for the squid nerve Na+/Ca2+ exchanger
      based on experimental evidences obtained in dialyzed axons. This model
      satisfactorily explains the interrelationship between ionic (Na+(i)-H+(i)
      Ca2+(i)) and metabolic (ATP, phosphoarginine (PA)) regulation of the exchanger.
      Data in dialyzed axons show that the Ca(i)-regulatory site located in the large
      intracellular loop plays a central role in the modulation by ATP by antagonizing
      the inhibitory Na+(i)-H+(i) synergism. We have used the Na(o)/Na(i) exchange mode
      to unequivocally measure the affinity of the Ca(i)-regulatory site. This allowed
      us to separate Ca(i)-regulatory from Ca(i)-transport sites and to estimate their
      respective affinities. In this work we show for the first time that under
      conditions of saturation of the Ca(i)-regulatory site (10 microM Ca2+(i), pH(i)
      8.0), ATP have no effect on the Ca(i)-transport site. In addition, we have
      expanded our equilibrium kinetic model of ionic and metabolic interactions to a
      complete exchange cycle (circular model). This model, in which the Ca(i)
      regulatory site plays a central role, accounts for the decrease in Na(i)
      inactivation, at high pH(i), high Ca2+(i,) and MgATP. Furthermore, the model also
      predicts the net Ca2+ movements across the exchanger based on the exchanger
      complexes redistribution both during physiological and pathological conditions
      (ischemia).

PMID- 17446452
TI  - Some biochemical properties of the upregulation of the squid nerve Na+/Ca2+
      exchanger by MgATP and phosphoarginine.
AB  - In squid nerve MgATP upregulation of Na+/Ca2+ exchange requires a soluble
      cytosolic regulatory protein (SCRP) of about 13 kDa; phosphoarginine (PA)
      stimulation does not. MgATP-gamma-S mimics MgATP. When a 30-10-kDa cytosolic
      fraction is exposed to 0.5 mM [32P]ATP in the same solution used for transport
      assays, and in the presence of native membrane vesicles, a 13-kDa and a 25-kDa
      band become phosphorylated. Membrane vesicles alone do not show these
      phosphorylated bands and heat denaturation of the cytosolic fraction prevents
      phosphorylation. Moreover, staurosporine, a general inhibitor of kinases, does
      not affect MgATP + SCRP stimulation of the exchanger or the phosphorylation of
      the 13 kDa but prevents phosphorylation of the 25-kDa cytosolic band. The 30-10
      kDa fraction phosphorylated in the presence of staurosporine stimulates Na+/Ca2+
      exchange in vesicles in the absence of ATP but with Mg2+ in the medium. The 30-10
      kDa fraction is not phosphorylated by PA. In membrane vesicles two protein bands,
      at about 60 kDa and 70 kDa identified as the low molecular weight neurofilament
      (NF), are phosphorylated by PA, but not by MgATP. This phosphorylation is
      specific for PA, insensitive to staurosporine (similar to the PA-stimulated
      fluxes), and labile. In addition, co-immunoprecipitation was observed between the
      NF and the exchanger protein. Under the conditions of these experiments no
      phosphorylation of the exchanger is detected, either with MgATP or PA.

PMID- 17446453
TI  - Ionic selectivity of NCKX2, NCKX3, and NCKX4 for monovalent cations at K+-binding
      site.
AB  - To determine the ionic selectivity of K+-sites in three members of Na+/Ca2++K+
      exchanger (NCKX) family: NCKX2, NCKX3 and NCKX4, we compared the amplitudes of
      reverse mode NCKX current (I(NCKX)) activated by K+-substitutes (Rb+, NH4+, Cs+,
      or Li+) relative to that by K+ in an HEK293 cell overexpressing each of NCKX
      isoforms. In all three isoforms, monovalent cations activated I(NCKX) with
      similar order of potency: K+ > Rb+ > NH4+ > Cs+ >> Li+. However, the relative
      potency of Cs+ and NH4+ for activating NCKX2 was significantly higher than those
      for NCKX3 and NCKX4, indicating that the selectivity of NCKX2 for K+ is weaker
      than the other two isoforms.

PMID- 17446454
TI  - In bovine heart Na+/Ca2+ exchanger maximal Ca2+i affinity requires simultaneously
      high pHi and PtdIns-4,5-P2 binding to the carrier.
AB  - Na+ i-dependent Ca2+ uptake, Na+-dependent Ca2+ release, and PtdIns-4,5-P2
      binding to Na+/Ca2+ exchanger (NCX1) as a function of extravesicular
      (intracellular) [Ca2+] were measured. Alkalinization increases Ca2+ i affinity
      and PtdIns-4,5-P2 bound to NCX1; these effects are abolished by pretreatment with
      PtdIns-PLC and are insensitive to MgATP. Acidification reduces Ca2+ i affinity.
      MgATP reverts it only partially despite the fact that the PtdIns-4,5-P2 bound to
      NCX1 reaches the same levels as at pH 7.8. Extravesicular Na+-stimulated and Ca2+
      dependent Ca2+ efflux indicate the Ca2+ regulatory site is involved. Therefore,
      to display maximal affinity to Ca2+ i, PtdIns-4,5-P2 binding and deprotonation of
      NCX1 are simultaneously need.

PMID- 17446455
TI  - NCX current in the murine embryonic heart: development-dependent regulation by
      Na+.
AB  - Due to its high functional expression, I(NCX) may serve as an important mechanism
      to ensure intracellular Ca2+ homeostasis, especially during the early embryonic
      stage. At the fetal stage I(NCX) density is significantly decreased but underlies
      regulatory processes, that is, regulation by Na+.

PMID- 17446457
TI  - Roles of NCX and PMCA in basolateral calcium export associated with
      mineralization cycles and cold acclimation in crayfish.
AB  - Basolateral Na+/Ca2+ exchanger (NCX) and plasma membrane Ca2+ ATPase (PMCA) are
      the primary transmembrane proteins that export calcium (Ca2+) from cells. In our
      lab we use a nonmammalian animal model, the freshwater crayfish, to study
      cellular Ca2+ regulation. Two experimental conditions are employed to effect Ca2+
      dyshomeostasis: (a) in the postmolt stage of the crustacean molting cycle
      increased unidirectional Ca2+ influx associated with cuticular mineralization is
      accompanied by elevated basolateral Ca2+ export (compared with intermolt Ca
      balance); and (b) exposure of the poikilothermic crayfish to cold acclimation (4
      degrees C) causes influx of Ca2+ into cells, which is compensated by increased
      basolateral Ca2+ export (compared with exposure to 23 degrees C). This study
      compares expression of both NCX and PMCA mRNA (real-time PCR) and protein
      (Western) in both epithelial (kidney) and nonepithelial tissue (tail muscle)
      during elevated basolateral Ca2+ export. Both experimental treatments produced
      increases in NCX and PMCA expression (mRNA and protein) in both tissues.
      Mineralization produced greater upregulation of mRNA in kidney than in tail,
      whereas cold acclimation yielded comparable increases in both tissues. Protein
      expression patterns were generally confirmatory of real-time PCR data although
      expression changes were less pronounced. Both experimental treatments appear to
      increase basolateral Ca2+ export.

PMID- 17446456
TI  - Gender differences in Na/Ca exchanger current and beta-adrenergic responsiveness
      in heart failure in pig myocytes.
AB  - Clinical trials suggest females experience less heart failure (HF) progression,
      mortality, and arrhythmia frequency. HF increases Na/Ca exchanger (NCX)
      expression and activity contributing to both depressed contractility and
      ventricular arrhythmias, but whether gender modifies this effect is unknown. Left
      ventricular myocytes were isolated from control and from tachycardic pacing
      induced failing swine hearts of both sexes. The Ni-sensitive NCX current (I(NCX))
      was measured in voltage clamp after blocking other channels. In control myocytes
      there is no difference in basal I(NCX) and beta-adrenergic responsiveness between
      male and female animals. HF greatly increased I(NCX) and reduced beta-adrenergic
      responsiveness in males compared to females, an effect that was eliminated by
      PP1. Diuretic therapy (furosemide, 1 mg/kg/day) further enhanced I(NCX) and
      reduced beta-adrenergic responsiveness in females and eliminated the gender
      difference. Gender-specific differences in calcium handling may contribute to
      improved survival of females in HF.

PMID- 17446458
TI  - Modulation pathways of NCX mRNA stability: involvement of RhoB.
AB  - Cardiac Na+/Ca2+ exchanger 1 (NCX1) expression levels change under various
      pathophysiological conditions. However, its mechanism is unknown. We found that
      fluvastatin, an HMG-CoA reductase inhibitor, decreased NCX1 mRNA and protein by
      inhibiting a small G protein, RhoB, in H9c2 cardiomyoblasts. Conversely,
      lysophosphatidylcholine (LPC) increased NCX1 mRNA and protein by activating RhoB.
      The effect of LPC was mediated by geranylgeranylation but not farnesylation of
      RhoB. Furthermore, we also detected that activation of RhoB increased NCX1 mRNA
      stability. Our results suggest that RhoB is involved in modulation of cardiac
      NCX1 mRNA expression.

PMID- 17446459
TI  - Regulation of Ncx1 gene expression in the normal and hypertrophic heart.
AB  - The Na+/Ca2+ exchanger (NCX1) is crucial in the regulation of [Ca2+]i in the
      cardiac myocyte. The exchanger is upregulated in cardiac hypertrophy, ischemia,
      and failure. This upregulation can have an effect on Ca2+ transients and possibly
      contribute to diastolic dysfunction and an increased risk of arrhythmias. Studies
      from both in vivo and in vitro model systems have provided an initial skeleton of
      the potential signaling pathways that regulate the exchanger during development,
      growth, and hypertrophy. The Ncx1 gene is upregulated in response to alpha
      adrenergic stimulation. We have shown that this is via p38alpha activation of
      transcription factors binding to the Ncx1 promotor at the -80 CArG element.
      Interestingly, most of the elements, including the CArG element, which we have
      demonstrated to be important for regulation of Ncx1 expression are in the
      proximal 184 bp of the promotor. Using a transgenic mouse, we have shown that the
      proximal 184 bp is sufficient for expression of reporter genes in adult
      cardiomyocytes and for the correct spatiotemporal pattern of Ncx1 expression in
      development but not for upregulation in response to pressure overload.

PMID- 17446460
TI  - Cyclosporin A-dependent downregulation of the Na+/Ca2+ exchanger expression.
AB  - Cyclosporin A (CsA) is an immunosuppressive drug commonly given to transplant
      patients. Its application is accompanied by severe side effects related to
      calcium, among them hypertension and nephrotoxicity. The Na+/Ca2+ exchanger (NCX)
      is a major calcium regulator expressed in the surface membrane of all excitable
      and many nonexcitable tissues. Three genes, NCX1, NCX2, and NCX3 code for
      Na+/Ca2+ exchange activity. NCX1 gene products are the most abundant. We have
      shown previously that exposure of NCX1-transfected HEK 293 cells to CsA, leads to
      concentration-dependent reduction of Na+/Ca2+ exchange activity and surface
      expression, without a reduction in total cell-expressed NCX1 protein. We show now
      that the effect of CsA on NCX1 protein expression is not restricted to
      transfected cells overexpressing the NCX1 protein but exhibited also in cells
      expressing endogenously the NCX1 protein (L6, H9c2, and primary smooth muscle
      cells). Exposure of NCX2- and NCX3-transfected cells to CsA results also in
      reduction of Na+/Ca2+ exchange activity and surface expression, though the
      sensitivity to the drug was lower than in NCX1-transfected cells. Studying the
      molecular mechanism of CsA-NCX interaction suggests that cyclophilin (Cyp) is
      involved in NCX1 protein expression and its modulation by CsA. Deletion of 426
      amino acids from the large cytoplasmic loop of the protein retains the CsA
      dependent downregulation of the truncated NCX1 suggesting that CsA-Cyp-NCX
      interaction involves the remaining protein domains.

PMID- 17446461
TI  - Functional significance of Na+/Ca2+ exchangers co-localization with ryanodine
      receptors.
AB  - Co-localization of Na+/Ca2+ exchangers (NCX) with ryanodine receptors (RyRs) is
      debated. We incorporate local NCX current in a biophysically detailed model of L
      type Ca2+ channels (LCCs) and RyRs and study the effect of NCX on the regulation
      of Ca2+-induced Ca2+ release and the shape of the action potential. In canine
      ventricular cells, under pathological conditions, e.g., impaired LCCs, local NCXs
      become an enhancer of sarcoplasmic reticulum release. Under such conditions
      incorporation of local NCXs is critical to accurately capture mechanisms of
      excitation-contraction coupling.

PMID- 17446462
TI  - Three types of muscles express three sodium-calcium exchanger isoforms.
AB  - The sodium-calcium exchanger (NCX) of plasma membrane is expressed in any animal
      cell. The specific role of its three isoforms (NCX1-3) is not yet established.
      Their levels vary considerably during murine postnatal development. In
      particular, in skeletal muscle, NCX1 expression decreases gradually upon aging
      while reciprocal changes take place for NCX3. NCX2 expression is restricted to
      brain and smooth muscles. The data on SDS-gel mobility shifts indicate that all
      three isoforms undergo Ca2+-dependent conformational changes, and that an
      exchanger regulatory Ca2+-binding domain interacts directly with mutually
      exclusive exons A and B inducing two different NCX1 conformations.

PMID- 17446463
TI  - Plasma membrane Ca2+ ATPases as dynamic regulators of cellular calcium handling.
AB  - Plasma membrane Ca2+ ATPases (PMCAs) are essential components of the cellular
      toolkit to regulate and fine-tune cytosolic Ca2+ concentrations. Historically,
      the PMCAs have been assigned a housekeeping role in the maintenance of
      intracellular Ca2+ homeostasis. More recent work has revealed a perplexing
      multitude of PMCA isoforms and alternative splice variants, raising questions
      about their specific role in Ca2+ handling under conditions of varying Ca2+
      loads. Studies on the kinetics of individual isoforms, combined with expression
      and localization studies suggest that PMCAs are optimized to function in Ca2+
      regulation according to tissue- and cell-specific demands. Different PMCA
      isoforms help control slow, tonic Ca2+ signals in some cells and rapid, efficient
      Ca2+ extrusion in others. Localized Ca2+ handling requires targeting of the pumps
      to specialized cellular locales, such as the apical membrane of cochlear hair
      cells or the basolateral membrane of kidney epithelial cells. Recent studies
      suggest that alternatively spliced regions in the PMCAs are responsible for their
      unique targeting, membrane localization, and signaling cross-talk. The regulated
      deployment and retrieval of PMCAs from specific membranes provide a dynamic
      system for a cell to respond to changing needs of Ca2+ regulation.

PMID- 17446464
TI  - Functional specificity of PMCA isoforms?
AB  - In mammals, four different genes encode four PMCA isoforms. PMCA1 and PMCA4 are
      expressed ubiquitously. PMCA2 and PMCA3 are expressed prevalently in the central
      nervous systems. More than 30 variants are generated by mechanisms of alternative
      splicing. The physiological meaning of the existence of such elevated number of
      isoforms is not clear, but it would be plausible to relate it to the cell
      specific demands of Ca2+ homeostasis. To characterize functional specificity of
      PMCA variants we have investigated two aspects: the effects of the overexpression
      of the different PMCA variants on cellular Ca2+ handling and the existence of
      possible isoform-specific interactions with partner proteins using a yeast two
      hybrid technique. The four basic PMCA isoforms were coexpressed in CHO cells
      together with the Ca2+-sensitive recombinant photoprotein aequorin. The effects
      of their overexpression on Ca2+ homeostasis were monitored in the living cells.
      They had revealed that the ubiquitous isoforms 1 and 4 are less effective in
      reducing the Ca2+ peaks generated by cell stimulation as compared to the neuron
      specific isoforms 2 and 3. To establish whether these differences were related to
      different and new physiological regulators of the pump, the 90 N-terminal
      residues of PMCA2 and PMCA4 have been used as baits for the search of molecular
      partners. Screening of a human brain cDNA library with the PMCA4 bait specified
      the epsilon-isoform of protein 14-3-3, whereas no 14-3-3 epsilon clone was
      obtained with the PMCA2 bait. Overexpression of PMCA4/14-3-3 epsilon (but not of
      PMCA2/14-3-3 epsilon) in HeLa cells together with targeted aequorins showed that
      the ability of the cells to export Ca2+ was impaired. Thus, the interaction with
      14-3-3 epsilon inhibited PMCA4 but not PMCA2. The role of PMCA2 has been further
      characterized by Ca2+ measurements in cells overexpressing different splicing
      variants. The results indicated that the combination of alternative splicing at
      two different sites in the pump structure was responsible for different
      functional characteristics of the pumps.

PMID- 17446465
TI  - Plasma membrane calcium ATPase and its relationship to nitric oxide signaling in
      the heart.
AB  - The plasma membrane calcium/calmodulin-dependent ATPase (PMCA) is a ubiquitously
      expressed calcium-extruding enzymatic pump. In the majority of cells the main
      function of PMCA is as the only system to extrude calcium from the cytosol,
      however, in the excitable cells of the heart it has only a minor role in the bulk
      removal of calcium compared to the sodium-calcium exchanger. There is increasing
      evidence to suggest that PMCA has an additional role as a potential modulator of
      a number of signal transduction pathways. Of key interest in the heart is the
      functional interaction between the calcium/calmodulin-dependent enzyme neuronal
      nitric oxide synthase (nNOS) and isoform 4 of PMCA. Nitric oxide production from
      nNOS is known to be important in the regulation of excitation-contraction (EC)
      coupling and subsequently contractility. This article will focus on recent
      evidence suggesting that PMCA4 has a regulatory role in the nitric oxide
      signaling pathway in the heart.

PMID- 17446466
TI  - Functional importance of PMCA isoforms in growth and development of PC12 cells.
AB  - Intracellular Ca2+ in neuronal cells is an essential regulatory ion responsible
      for excitability, synaptic plasticity, and neurite outgrowth. Plasma membrane
      calcium ATPase (PMCA) is the most sensitive enzyme in decreasing of the Ca2+
      concentration. The diverse PMCA isoforms composition in the membranes suggests
      their specific function in the cell, and whereas PMCA1 and 4 appear to be
      ubiquitous, PMCA2 and 3 are characteristic isoforms for excitable cells. The aim
      of our study was to elucidate if and how the elimination of neuron-specific
      isoforms affects the pattern of cell growth and development. We have obtained
      stable-transfected PC12 cell lines with a suppressed expression of PMCA2, PMCA3,
      or both neuron-specific isoforms. The modified profile of PMCA generated
      considerable changes in morphology of examined PC12 lines, suggesting the
      activation of a differentiation process to pseudoneuronal phenotype. Experiments
      with Fura-2/AM-loaded cells revealed an increased cytosolic Ca2+ concentration in
      the cell lines with blocked PMCA2 isoform. The suppression of PMCA2 concomitantly
      altered expression of sarco/endoplasmic Ca2+-ATPase 2 isoform (SERCA2) at the
      protein level. Comparative flow cytometry analysis, using Annexin V/PI conjugate,
      showed the difference in the mean percentage of apoptotic cells in modified PC12
      lines. Our data suggest that specific PMCA isoforms presence can regulate the
      intact cell development; however, it may involve multiple unidentified yet
      signaling pathways.

PMID- 17446467
TI  - Na+/Ca2+ exchanger knockout mice: plasticity of cardiac excitation-contraction
      coupling.
AB  - The Na+/Ca2+ exchanger (NCX) is the main Ca2+ extrusion mechanism of the cardiac
      myocyte. Nevertheless, cardiac-specific NCX knockout (KO) mice are viable to
      adulthood. We have identified two adaptations of excitation-contraction coupling
      (ECC) to the absence of NCX in these animals: (a) a reduction of the L-type Ca2+
      current (I(Ca)) with an increase in ECC gain and (b) a shortening of the action
      potential (AP) to further limit Ca2+ influx. Both mechanisms contribute to Ca2+
      homeostasis by reducing Ca2+ influx while maintaining contractility. These
      adaptations may comprise important feedback mechanisms by which cardiomyocytes
      may be able to limit Ca2+ influx in situations of compromised Ca2+ extrusion
      capacity.

PMID- 17446468
TI  - Distinct phenotypes among plasma membrane Ca2+-ATPase knockout mice.
AB  - Ca2+ gradients across the plasma membrane, required for Ca2+ homeostasis and
      signaling, are maintained in part by plasma membrane Ca2+-ATPase (PMCA) isoforms
      1-4. Gene targeting has been used to analyze the functions of PMCA1, PMCA2, and
      PMCA4 in mice. PMCA1 null mutant embryos die during the preimplantation stage,
      and loss of a single copy of the PMCA1 gene contributes to apoptosis in vascular
      smooth muscle. PMCA2 deficiency in sensory hair cells of the inner ear causes
      deafness and balance defects, most likely by affecting both intracellular Ca2+
      and extracellular Ca2+ in the endolymph. PMCA2 is required for viability of
      certain neurons, consistent with a major role in maintenance of intracellular
      Ca2+. Surprisingly, loss of PMCA2 in lactating mammary glands causes a sharp
      reduction in milk Ca2+, consistent with a macrocalcium secretory function.
      Although PMCA4 is widely expressed and is the most abundant isoform in some
      tissues, null mutants appear healthy. However, male PMCA4 null mutants are
      infertile due to a failure of hyperactivated sperm motility resulting from the
      absence of PMCA4 in the sperm tail, and Ca2+ signaling in B lymphocytes,
      involving interactions between PMCA4, CD22, and the tyrosine phosphatase SHP-1,
      is defective. Studies of bladder smooth muscle from PMCA4 null mutants and PMCA1
      heterozygous mice suggest that PMCA1 and PMCA4 play different roles in smooth
      muscle contractility, with PMCA1 contributing to overall Ca2+ clearance and PMCA4
      being required for carbachol-stimulated contraction. These phenotypes indicate
      that PMCA1 serves essential housekeeping functions, whereas PMCA4 and
      particularly PMCA2 serve more specialized physiological functions.

PMID- 17446469
TI  - Role of plasma membrane calcium ATPase isoform 2 in neuronal function in the
      cerebellum and spinal cord.
AB  - The distinct role of plasma membrane calcium ATPase 2 (PMCA2) in the function of
      different neuronal subpopulations in the central nervous system is not well
      understood. We found that lack of PMCA2 leads to a reduction in the number of
      motor neurons in the spinal cord of PMCA2-null mice and to abnormal changes in
      molecular pathways in Purkinje cells. Thus, PMCA2 may have unique, nonredundant
      functions in spinal cord and cerebellar neurons. Our results suggest that
      anomalous alterations in PMCA2 activity or expression may induce pathology in
      some neuronal populations, a possibility that will be the focus of future
      investigations.

PMID- 17446470
TI  - Increased tolerance to ischemic neuronal damage by knockdown of Na+-Ca2+
      exchanger isoform 1.
AB  - We hypothesize that stimulation of Na+-K+-Cl+ cotransporter (NKCC1) causes Na+
      overload that may lead to reversal of Na+-Ca2+ exchanger isoform 1 (NCX1) and
      ischemic neuronal damage. NCX1 protein expression and Ca2+ influx via reversal of
      NCX were decreased by approximately 70% in NCX1+/- neurons. Compared to NCX1+/+
      neurons, NCX1+/- neurons exhibited significantly less cell death (approximately
      30%) after 3 h oxygen and glucose deprivation (OGD) and 21 h reoxygenation.
      Additional neuroprotection was found in NCX1+/- neurons treated with NCX
      inhibitor KB-R7943. Moreover, expression of NCX1 protein was approximately 40%
      lower in NCX1+/- brains than in NCX1+/+ brains. However, there was no significant
      reduction in cerebral infarction in NCX1+/- mice following middle cerebral artery
      occlusion (MCAO). These data suggest that moderate reduction of NCX1 protein may
      be not enough to exert protection. We used small RNA-interference (siRNA)
      approach to further elucidate the role of NCX1 in ischemic cell damage. Efficacy
      of anti-NCX1 siRNA was tested in astrocytes and approximately 50% knockdown of
      NCX1 protein expression was achieved after 24-72 h transfection. Reduction in
      NCX1 protein expression was also found in brains of NCX1+/- mice after the siRNA
      injection. NCX1+/- mice treated with siRNA showed approximately 20% less MCAO
      induced infarction, compared to NCX1+/- mice. Approximately 50% neuroprotection
      was detected in NKCC1+/-/NCX1+/- mice following MCAO. In conclusion, these data
      suggest that NCX1 plays an important role in ischemia/reperfusion-induced
      neuronal injury.

PMID- 17446471
TI  - Resistance of cardiac cells to NCX knockout: a model study.
AB  - The effects of NCX knockout were determined in a variety of cardiac cell models.
      Those of the mouse and rat ventricles, and of atrial cells in other species
      behave similarly to the experiments on mouse ventricle showing only small
      effects, and considerable tolerance of NCX knockout. Models of ventricular cells
      with high action potential plateaus, however, are more sensitive and require
      compensatory mechanisms to adjust other conductance parameters to enable the
      cells to resist NCX knockout. The effects can therefore be expected to be species
      specific, and it is not possible to extrapolate the mouse results to those that
      may occur in the Guinea pig or human.

PMID- 17446472
TI  - Homozygous overexpression of the Na+-Ca2+ exchanger in mice: evidence for
      increased transsarcolemmal Ca2+ fluxes.
AB  - Mice with homozygous overexpression of the Na+-Ca2+ exchanger (NCX) exhibit
      threefold levels of NCX expression and an increased Ca2+ extrusion rate. To
      investigate how Ca2+ homeostasis is maintained in this model, we have
      characterized Ca2+ influx under these conditions. We find that L-type Ca2+
      currents (I(Ca)) inactivate slower due to a reduction of Ca2+-dependent
      inactivation. Additionally, NCX-overexpressing animals exhibit a prolongation of
      the action potential (AP). We conclude that transsarcolemmal Ca2+ fluxes in NCX
      overexpressing myocytes are balanced by an increase in Ca2+ influx via (a) slowed
      inactivation of I(Ca) and (b) a prolongation of the AP to compensate for
      increased Ca2+ efflux.

PMID- 17446473
TI  - Na/Ca exchange: regulator of intracellular calcium and source of arrhythmias in
      the heart.
AB  - The major effect of Na/Ca exchange (NCX) on the systolic Ca transient is
      secondary to its effect on the Ca content of the sarcoplasmic reticulum (SR). SR
      Ca content is controlled by a mechanism in which an increase of SR Ca produces an
      increase in the amplitude of the systolic Ca transient. This, in turn, increases
      Ca efflux on NCX as well as decreasing entry on the L-type current resulting in a
      decrease of both cell and SR Ca content. This control mechanism also changes the
      response to other maneuvers that affect excitation-contraction coupling. For
      example, potentiating the opening of the SR Ca release channel (ryanodine
      receptor, RyR) with caffeine produces an immediate increase in the amplitude of
      the systolic Ca transient. However, this increases efflux of Ca from the cell on
      NCX and then decreases SR Ca content until a new steady state is reached.
      Changing the activity of NCX (by decreasing external Na) changes the level of SR
      Ca reached by this mechanism. If the cell and SR are overloaded with Ca then Ca
      waves appear during diastole. These waves activate the electrogenic NCX and
      thereby produce arrhythmogenic-delayed afterdepolarizations. A major challenge is
      how to remove this arrhythmogenic Ca release without compromising the normal
      systolic release. We have found that application of tetracaine to decrease RyR
      opening can abolish diastolic release while simultaneously potentiating the
      systolic release.

PMID- 17446474
TI  - Na/Ca exchange and cardiac ventricular arrhythmias.
AB  - Ventricular arrhythmias are a major cause of death in cardiovascular disease.
      Ca2+ removal from the cell by the electrogenic Na/Ca exchanger is essential for
      the Ca2+ flux balance during excitation-contraction coupling but also contributes
      to the electrical events. "Classic" views on the exchanger in arrhythmias include
      its well-recognized role as depolarizing current underlying delayed
      afterdepolarizations (DADs) during spontaneous Ca2+ release and the alterations
      in expression in certain forms of cardiac hypertrophy and heart failure. "Novel"
      views relate to more subtle roles for the exchanger in arrhythmias. Na/Ca
      exchange function in disease could be modulated indirectly, through
      phosphorylation or anchoring proteins. Ongoing studies relate Na/Ca exchange to
      variability in action potential duration (APD) and early afterdepolarizations
      (EADs) in a dog model of cardiac hypertrophy and arrhythmias. Further research on
      drugs that target Na/Ca exchange will have to carefully examine the effects on
      Ca2+ balance.

PMID- 17446475
TI  - The role of the cardiac Na+/Ca2+ exchanger in reverse remodeling: relevance for
      LVAD-recovery.
AB  - Different strategies can, at least in certain conditions, prevent or reverse
      myocardial remodeling due to heart failure and induce myocardial functional
      improvement. Na+/Ca2+ exchanger (NCX) is considered a major player in the
      pathophysiology of heart failure but its role in reverse remodeling is unknown. A
      combination of mechanical unloading by left ventricular assist devices (LVADs)
      and pharmacological therapy has been shown to induce clinical recovery in a
      limited number of patients with end-stage heart failure. In myocytes isolated
      from these patients we found that, after LVAD treatment, NCX1/SERCA2a mRNA was
      38% higher than at device implant. We studied the ability of NCX to extrude Ca2+
      during caffeine-induced SR Ca2+ release in isolated ventricular myocytes from
      these patients. The time constant of decline was slower in heart failure. In
      myocytes from patients with clinical recovery following mechanical and
      pharmacological treatment, NCX1-mediated Ca2+ extrusion was faster compared with
      myocytes from patient who, despite identical treatment, did not recover. We
      propose that increased NCX function may be associated with reverse remodeling in
      patients and that factors that regulate NCX function (i.e., phosphorylation or
      intracellular [Na+]) other than NCX expression levels alone, may have detrimental
      consequences on cardiac function.

PMID- 17446476
TI  - Regulation of Na+/Ca2+ exchange current in the normal and failing heart.
AB  - Cardiac NCX is modulated by diverse regulatory elements. Although there is
      consensus about the regulatory function of Na+ and Ca2+ and other elements, for
      example, ATP, there is still a controversial debate about the functional role of
      cyclic nucleotides and protein kinases. Future studies should focus on that topic
      since disturbances of cAMP/cGMP concentration and kinase activity may lead to
      severe functional disorders in the diseased heart. S100A1 is presumably a novel
      regulator of NCX.

PMID- 17446477
TI  - Phosphorylation of Na+/Ca2+ exchanger in TAB-induced cardiac hypertrophy.
AB  - Both protein kinase Calpha-dependent Na+/Ca2+ exchanger1 (NCX1) phosphorylation
      and calcineurin activity are required for the depression of NCX activity observed
      in chronically phenylephrine (PE)-treated hypertrophic neonatal rat
      cardiomyocytes. In this study, we explored the possibility that the same changes
      occur in vivo hypertrophy. In the hypertrophic hearts of thoracic aortic-banded
      (TAB) mice, NCX1 phosphorylation increased significantly compared with control
      hearts. Furthermore, the TAB-induced cardiac hypertrophy was much less prominent
      in transgenic mice overexpressing an NCX1 mutant having defective phosphorylation
      sites. These data suggest that the phosphorylation status of NCX1 may play an
      important role in the pathogenesis of load-induced cardiac hypertrophy.

PMID- 17446478
TI  - Role of Ca2+ transporters and channels in the cardiac cell volume regulation.
AB  - Na+/K+ pump is one of key mechanisms to maintain cell volume. When it is
      inhibited, cells are at risk of swelling. However, in guinea pig ventricular
      myocytes, the cell area as an index of cell volume was almost constant during 90
      min Na+/K+ pump blockade with 40 microM ouabain despite the marked membrane
      depolarization. In this study, involvements of Ca2+ transporters and channels in
      the cardiac cell volume regulation were proposed by conducting the computer
      simulation in parallel with the experimental validation.

PMID- 17446479
TI  - NCX and NCKX operation in ischemic neurons.
AB  - Within the first 2 min of global brain ischemia, extracellular [K+] ([K+]o)
      increases above 60 mM and [Na+](o) drops to about 50 mM, indicating a massive K+
      efflux and Na+ influx, a phenomenon known as anoxic depolarization (AD). Similar
      ionic shifts take place during repetitive peri-infarct depolarizations (PID) in
      the area penumbra in focal brain ischemia. The size of ischemic infarct is
      determined by the duration of AD and PID. However, the mechanism of cytosolic
      [Ca2+] ([Ca2+]c) elevation during AD or PID is poorly understood. Our data show
      that the exposure of cultured rat hippocampal CA1 neurons to AD-like conditions
      promptly elevates [Ca2+]c to about 30 microM. These high [Ca2+]c elevations
      depend on external Ca2+ and can be prevented by removing Na+ or by simultaneously
      inhibiting NMDA and AMPA/kainate receptors. These data indicate that [Ca2+]c
      elevations during AD result from Na+ influx via either NMDA or AMPA/kainate
      channels. The mechanism of the Na-dependent [Ca2+]c elevations may involve a
      reversal of plasmalemmal Na+/Ca2+ (NCX) and/or Na+/Ca2+ + K+ (NCKX) exchangers.
      KB-R7943, an NCX inhibitor, suppresses a fraction of the Na-dependent Ca2+ influx
      during AD. Therefore, Ca2+ influx via NCX and a KB-R7943-resistant pathway
      (possibly NCKX) is involved. Inhibition of the Na-dependent Ca2+ influx is likely
      to decrease ischemic brain damage. No drugs are known that are able to inhibit
      the KB-R7943-resistant component of Na-dependent Ca2+ influx during AD. The
      present data encourage development of such agents as potential therapeutic means
      to limit ischemic brain damage after stroke or heart attack.

PMID- 17446480
TI  - Na+/Ca2+ exchange and Ca2+ homeostasis in axon terminals of mammalian central
      neurons.
AB  - We investigated Ca2+ clearance mechanisms (CCMs) at the axon terminals of
      mammalian central neurons: neurohypophysial (NHP) axon terminals and calyces of
      Held. Ca2+ transients were evoked by applying a short depolarization pulse via a
      patch pipette containing Ca2+ indicator dye. Quantitative analysis of the Ca2+
      decay phases revealed that Na+/Ca2+ exchange (Na/CaX) is a major CCM at both axon
      terminals. In contrast, no Na/CaX activity was found in the somata of NHP axon
      terminals (supraoptic magnocellular neurons), indicating that the distribution of
      Na+/Ca2+ exchangers is polarized. Intracellular dialysis of axon terminals with a
      K+-free pipette solution attenuated the Na/CaX activities by 90% in the NHP axon
      terminals and by 60% at the calyx of Held, indicating that K+-dependent Na+/Ca2+
      exchangers are involved. Studying the effects of specific inhibitors of smooth
      endoplasmic reticulum Ca2+-ATPase (SERCA) and plasma membrane Ca2+-ATPase (PMCA)
      on the Ca2+ decay rate revealed that PMCA contributed 23% of total Ca2+
      clearance, but that SERCA made no contribution at the calyx of Held. The
      contribution of mitochondria was negligible for small Ca2+ transients, but became
      apparent at peak Ca2+ levels higher than 2.5 microM. When mitochondrial function
      was inhibited, the dependence of CCMs on [Ca2+]i at the calyx of Held showed
      saturation kinetics with K(1/2) = 1.7 microM, suggesting that the Na/CaX activity
      is saturated at high [Ca2+]i. The presynaptic Na+/Ca2+ exchanger activity, which
      competes for cytosolic Ca2+ with mitochondria, may contribute to nonplastic
      synaptic transmission at these axon terminals.

PMID- 17446481
TI  - ncx1, ncx2, and ncx3 gene product expression and function in neuronal anoxia and
      brain ischemia.
AB  - Over the last few years, although extensive studies have focused on the relevant
      function played by the sodium-calcium exchanger (NCX) during focal ischemia, a
      thorough understanding of its role still remains a controversial issue. We
      explored the consequences of the pharmacological inhibition of this antiporter
      with conventional pharmacological approach, with the synthetic inhibitory
      peptide, XIP, or with an antisense strategy on the extent of brain damage induced
      by the permanent occlusion of middle cerebral artery (pMCAO) in rats.
      Collectively, the results of these studies suggest that ncx1 and ncx3 genes could
      be play a major role to limit the severity of ischemic damage probably as they
      act to dampen [Na+]i and [Ca2+]i overload. This mechanism seems to be normally
      activated in the ischemic brain as we found a selective upregulation of NCX1 and
      NCX3 mRNA levels in regions of the brain surviving to an ischemic insult. Despite
      this transcript increase, NCX1, NCX2, and NCX3 proteins undergo an extensive
      proteolytic degradation in the ipsilateral cerebral hemisphere. All together
      these results suggest that a rescue program centered on an increase NCX function
      and expression could halt the progression of the ischemic damage. On the basis of
      this evidence we directed our attention to the understanding of the
      transductional and transcriptional pathways responsible for NCX upregulation. To
      this aim, we are studying whether the brain isoform of Akt, Akt1, which is a
      downstream effector of neurotrophic factors, such as NGF can, in addition to
      affecting the other prosurvival cascades, also exert its neuroprotective effect
      by modulating the expression and activity of ncx1, ncx2, and ncx3 gene products.

PMID- 17446482
TI  - Sodium-calcium exchanger in pulmonary artery smooth muscle cells.
AB  - The expression and function of the Na+/Ca2+ exchanger (NCX) in the regulation of
      intracellular Ca2+ homeostasis have been well studied in cardiac, skeletal, and
      systemic vascular myocytes, but not in pulmonary artery smooth muscle cells
      (SMCs). We have recently demonstrated that the NCX current is present in freshly
      isolated pulmonary artery SMCs using the patch-clamp technique. The current has a
      mean amplitude of 13 pA under near physiological resting conditions. The NCX may
      function in the forward mode to make a significant contribution to the decay of
      intracellular Ca2+ following Ca2+ release and/or depolarization. Hypoxic
      stimulation inhibits the NCX current, reduces the removal of intracellular Ca2+,
      and enhances Ca2+ release from the sarcoplasmic reticulum. Using RT-PCR,
      subcloning and sequence analysis, we have shown that three NCX1 splice variants:
      NCX1.2 (containing exons B, C, and D), NCX1.3 (exons B and D), and NCX1.7 (exons
      B, D, and F) are expressed in pulmonary artery smooth muscle. Each of these
      splice variants expressed in HEK293 cells it likely to show a distinct activity
      in the removal of intracellular Ca2+. Taken together, we provide clear evidence
      that NCX1 is functionally and molecularly expressed and plays a physiological
      role in pulmonary artery SMCs.

PMID- 17446483
TI  - Rapid downregulation of NCX and PMCA in hippocampal neurons following H2O2
      oxidative stress.
AB  - Na+/Ca2+ exchangers (NCXs) and plasma membrane Ca2+ pumps (PMCAs) are crucial for
      intracellular Ca2+ homeostasis and Ca2+ signaling. Elevated [Ca2+]i is a hallmark
      of neurodegenerative disease and stroke. Here we studied the short-term effect of
      oxidative stress on the plasma membrane Ca2+ extrusion systems in hippocampal
      neurons (HN) and found that after 2-3 h exposure to 300 microM H2O2, all NCXs and
      PMCAs were significantly downregulated at the RNA (NCX) and protein (PMCA) level.
      Rapid internalization and aggregation of the PMCA was also observed. Our data
      show that the plasma membrane calcium extrusion systems are sensitive early
      targets of neurotoxic oxidative stress.

PMID- 17446484
TI  - Cleavage of the plasma membrane Ca+ATPase during apoptosis.
AB  - Maintenance of Ca2+ homeostasis is essential for normal cellular function and
      survival. Recent evidences suggest that Ca2+ is also an important player of
      apoptosis. We demonstrated that the plasma membrane Ca2+ ATPase (PMCA) isoform
      4b, a key element of cellular Ca2+ homeostasis, was cleaved by caspase-3 during
      the course of apoptosis. This cleavage of PMCA removed the entire regulatory
      region from the C terminus, leaving behind a 120-kDa catalytic fragment. Since
      loss of PMCA activity could lead to intracellular Ca2+ overload and consequently
      necrotic cell death, an important question is whether the apoptotic fragment of
      PMCA retains full activity or it is inactivated. To address this question, we
      constructed a C-terminally truncated mutant that corresponded to the caspase-3
      fragment of PMCA4b and showed that it was fully and constitutively active. This
      mutant was targeted properly to the plasma membrane when it was expressed stably
      or transiently in several different cell lines. We followed truncation of PMCA
      during apoptosis induced by mitochondrial or receptor-mediated pathways and found
      that a similar fragment of 120 kDa was formed and remained intact for several
      hours after treatment. We have also demonstrated that the caspase-3 cleavage site
      is an important structural element of PMCA and found that the accessibility of
      the caspase-3 site depended strongly on the conformational state of the protein.

PMID- 17446485
TI  - The plasma membrane Na+/Ca2+ exchanger is cleaved by distinct protease families
      in neuronal cell death.
AB  - Neurodegenerative conditions commonly involve loss of neuronal connectivity,
      synaptic dysfunction with excessive pruning, and ionic imbalances. These often
      serve as a prelude to cell death either through the activation of apoptotic or
      necrotic death routines or excess autophagy. In many instances, a local or
      generalized Ca2+ deregulation is involved in signaling or executing cell death.
      We have recently shown that in brain ischemia, and during excitotoxicity
      triggered by excess glutamate, the irreversible Ca2+ deregulation leading to
      necrosis is due to calpain-mediated modulation of the plasma membrane Na+/Ca2+
      exchanger (NCX). Here we show that the NCX can also be cleaved by caspases in
      neurons undergoing apoptosis, which suggests that cleavage of the main Ca2+
      extrusion pathway is a lethal event in multiple forms of cell death.

PMID- 17446486
TI  - Role of Na/Ca exchange and the plasma membrane Ca2+-ATPase in beta cell function
      and death.
AB  - Recent progresses concerning the Na/Ca exchanger (NCX) and the plasma membrane
      Ca2+-ATPase (PMCA) in the pancreatic beta cell are reviewed. The rat beta cell
      expresses two splice variants of NCX1 and six splice variants of the 4 PMCA
      isoforms. At the protein level, the most abundant forms are PMCA2 and PMCA3,
      providing the first evidence for the presence of these two isoforms in a non
      neuronal tissue. Overexpression of NCX1 in an insulinoma cell line altered the
      initial rise in cytosolic-free Ca2+ concentration ([Ca2+]i) induced by membrane
      depolarization and the return of the [Ca2+]i to the baseline value on membrane
      repolarization, indicating that NCX contributes to both Ca2+ inflow and outflow
      in the beta cell. In contrast, overexpression of the PMCA markedly reduced the
      global rise in Ca2+ induced by membrane depolarization, indicating that the PMCA
      has a capacity higher than expected to extrude Ca2+. Glucose, the main
      physiological stimulus of insulin release from the beta cell, has opposite effect
      on NCX and PMCA transcription, expression and activity, inducing an increase in
      the case of NCX and a decrease in the case of the PMCA. This indicates that when
      exposed to glucose, the beta cell switches from a low-efficiency Ca2+ extruding
      mechanism, the PMCA, to a high-capacity system, the NCX, in order to better face
      the increase in Ca2+ inflow induced by the sugar. To our knowledge, this is the
      first demonstration of a reciprocal change in PMCA and NCX1 expression and
      activity in response to a given stimulus in any tissue.

PMID- 17446487
TI  - Overexpression of Na/Ca exchanger reduces viability and proliferation of
      gliosarcoma cells.

PMID- 17446488
TI  - Redox modulation of the apoptogenic activity of thapsigargin.
AB  - Thapsigargin (THG), a selective inhibitor of endoplasmic reticulum (ER) Ca2+
      ATPases, causes the rapid emptying of ER Ca2+; in some cell types, this is
      accompanied by apoptosis, whereas other cells maintain viability. In order to
      understand the molecular determinants of such a different behavior, we explored
      the role of oxygen versus nitrogen radicals, by analyzing the apoptogenic ability
      of THG in the presence of inhibitors of glutathione or nitric oxide (NO)
      synthesis, respectively. We observed that oxygen radicals play a sensitizing role
      whereas nitrogen radicals prevent THG-dependent apoptosis, showing that the
      apoptogenic effect of THG is redox sensitive.

PMID- 17446489
TI  - The role of Na+/Ca2+ exchanger in endothelin-1-aggravated hypoxia/reoxygenation
      induced injury in renal epithelial cells.
AB  - We analyzed the role of the Na+/Ca2+ exchanger (NCX) in endothelin-1-aggravated
      hypoxia/reoxygenation-induced injury in renal epithelial LLC-PK1 cells. KB-R7943,
      a selective NCX inhibitor, suppressed hypoxia/reoxygenation-induced cell damage,
      whereas overexpression of NCX1 into cells enhanced it. Endothelin-1 significantly
      aggravated hypoxia/reoxygenation-induced injury in parental and NCX1
      overexpressing LLC-PK1 cells. Such aggravation by endothelin-1 was not observed
      in cells overexpressing a deregulated NCX1 mutant, which displays no protein
      kinase C-dependent activation. These results suggest that Ca2+ overload via NCX
      plays a critical role in hypoxia/reoxygenation-induced renal tubular injury, and
      that endothelin-1 aggravates the cell damage through the activation of NCX.

PMID- 17446490
TI  - The Na+/Ca2+ exchanger isoform 3 (NCX3) but not isoform 2 (NCX2) and 1 (NCX1)
      singly transfected in BHK cells plays a protective role in a model of in vitro
      hypoxia.
AB  - Chemical hypoxia produces depletion of ATP, intracellular Ca2+ overload, and cell
      death. The role of Na+/Ca2+ exchanger (NCX), the major plasma membrane Ca2+
      extruding system, has been explored in chemical hypoxia using BHK cells stably
      transfected with the three mammalian NCX isoforms: NCX1, NCX2, and NCX3. Here we
      report that the three isoforms show similar activity evaluated as [Ca2+]i
      increase evoked by Na+-free medium exposure in Fura-2-loaded single cells and
      NCX3 transfected cells are less vulnerable to chemical hypoxia compared to NCX1-
      and NCX2-transfected cells, suggesting that NCX3 could play a more relevant
      protective role during chemical hypoxia.

PMID- 17446491
TI  - Involvement of the potassium-dependent sodium/calcium exchanger gene product
      NCKX2 in the brain insult induced by permanent focal cerebral ischemia.
AB  - Sodium/calcium exchangers are neuronal plasma membrane transporters, which by
      coupling Ca2+ and Na+ fluxes, may play a relevant role in brain ischemia. The
      exchanger gene superfamily comprises two arms: the K+-independent (NCX) and K+
      dependent (NCKX) exchangers. In the brain, three different NCX (NCX1, NCX2, NCX3)
      and three NCKX (NCKX2, NCKX3, NCKX4) family members have been described. Up to
      now, no sutides about the role played by NCKX proteins in cerebral ischemia have
      been published. The aim of the present study was to investigate the role of NCKX2
      in an in vivo model of permanent middle cerebral artery occlusion (pMCAO). The
      role of this protein in the development of ischemic damage was assessed by
      knocking-down its expression with an antisense oligodeoxynucleotide (AS-ODN),
      intracerebroventricularly infused by an osmotic minipump for 48 h, starting from
      24 h before pMCAO. The results showed that NCKX2 knocking-down by using antisense
      strategy increased the extent of the ischemic lesion. The results of this study
      suggest that NCKX2 could exert a neuroprotective effect during ischemic injury.

PMID- 17446492
TI  - Analysis of calcium changes in endoplasmic reticulum during apoptosis by the
      fluorescent indicator chlortetracycline.
AB  - Many studies suggest that endoplasmic reticulum (ER) Ca2+ pool rather than
      cytosolic Ca2+ may play a crucial role in triggering apoptosis. In this study, we
      performed an image analysis of cells loaded with the fluorescent dye
      chlortetracycline (CTC) to in situ analyze Ca2+ changes within the ER in
      apoptosing promonocytic U937 cells. The results, validated through the use of
      thapsigargin (THG) as ER Ca2+ depletor, confirm the findings that apoptotic cells
      have a Ca2+-depleted ER, in contrast with treated but still viable cells.

PMID- 17446493
TI  - Sodium-calcium exchangers in the nucleus: an unexpected locus and an unusual
      regulatory mechanism.
AB  - Whereas sodium-calcium exchangers (NCXs) have long been recognized as plasma
      membrane constituents that serve to maintain homeostatic concentrations of Ca2+
      in the cytoplasm, they were recently shown to also occur in the nuclear envelope
      (NE) of neural and other cells where they function to regulate nuclear Ca2+. A
      unique feature of NCXs in the NE is their high-affinity binding to GM1
      ganglioside, this association being required for optimal exchanger activity. The
      NCX-GM1 complex occurs in the inner membrane of the NE and transfers Ca2+ from
      the nucleoplasm to the NE lumen. In neuronal cells, nuclear GM1 levels are low
      prior to differentiation but increase rapidly as axonal outgrowth progresses.
      Cells from genetically altered mice lacking GM1 have limited ability to regulate
      nuclear Ca2+, and the mice themselves showed similar deficit as seen in their
      high susceptibility to kainite-induced seizures. These are attenuated by LIGA-20,
      a derivative of GM1 that enters the nuclear membrane and restores nuclear NCX
      activity to normal level.

PMID- 17446494
TI  - Mitochondrial Ca2+ flux through Na+/Ca2+ exchange.
AB  - To clarify the property of mitochondrial Na+/Ca2+ exchange in situ, we measured
      mitochondrial Ca2+ using Rhod-2 in permeabilized rat ventricular myocytes.
      Cytoplasmic 300 nM Ca2+ (Ca2+(c)) augmented the Rhod-2 intensity by approximately
      ninefolds without cytoplasmic Na+ (Na+(c)). Increasing Na+(c) attenuated the
      maximum level of Rhod-2 fluorescence, probably due to the activation of forward
      mode of mitochondrial Na+/Ca2+ exchange. The Rhod-2 intensity decayed upon
      removing Ca2+(c). The decay was dependent on Na+(c) (K(1/2) = approximately 1 mM)
      and largely abolished by an inhibitor of mitochondrial Na+/Ca2+ exchange, CGP
      37157. It was suggested that Na+ binding to the mitochondrial Na+/Ca2+ exchange
      is saturated in the physiological concentration of Na+(c).

PMID- 17446495
TI  - Non-apoptogenic Ca2+-related extrusion of mitochondria in anoxia/reoxygenation
      stress.
AB  - Tumor cells often develop molecular strategies for survival to
      anoxia/reoxygenation stress as part of tumor progression. Here we describe that
      the B lymphoma Epstein-Barr-positive cells E2r survive reoxygenation in spite of
      a very high and long-lasting increase in cytosolic Ca2+ and the loss of about
      half of their mitochondria due to specific extrusion of the organelles from the
      cells. The extrusion typically occurs 3 days after reoxygenation, and a regular
      mitochondrial asset is regained after further 24 h.

PMID- 17446496
TI  - Na+/Ca2+ exchange as a drug target--insights from molecular pharmacology and
      genetic engineering.
AB  - The Na+/Ca2+ exchanger (NCX) is an ion transporter that exchanges Na+ and Ca2+ in
      either Ca2+-efflux or Ca2+-influx mode, depending on membrane potential and
      transmembrane ion gradients. In myocytes, neurons, and renal tubular cells, NCX
      is thought to play an important role in the regulation of intracellular Ca2+
      concentration. So far the benzyloxyphenyl derivatives (KB-R7943, SEA0400, SN-6,
      and YM-244769) have been developed as selective NCX inhibitors. These inhibitors
      possess different isoform selectivities, although they have similar properties,
      such as Ca2+-influx mode selectivity and I1 inactivation-dependence. Site
      directed mutageneses have revealed that these inhibitors possess some molecular
      determinants (Phe-213, Val-227, Tyr-228, Gly-833, and Asn-839) for interaction
      with NCX1. These benzyloxyphenyl derivatives are expected to be useful tools to
      study the physiological roles of NCX. Interestingly, benzyloxyphenyl NCX
      inhibitors effectively prevent several ischemia-reperfusion injuries and salt
      dependent hypertension in animal models. Furthermore, several experiments with
      genetically engineered mice provide compelling evidence that these diseases are
      triggered by pathological Ca2+ entry through NCX1. Thus, NCX inhibitors may have
      therapeutic potential as novel drugs for reperfusion injury and salt-dependent
      hypertension.

PMID- 17446497
TI  - Inhibitory mechanism of SN-6, a novel benzyloxyphenyl Na+/Ca2+ exchange
      inhibitor.
AB  - We investigated the pharmacological properties of SN-6, a new selective Na+/Ca2+
      exchanger (NCX) inhibitor. SN-6 preferentially inhibited the (45)Ca2+ uptake via
      NCX compared with the (45)Ca2+ efflux via NCX in NCX-transfected fibroblasts. SN
      6 was three- to fivefold more inhibitory to the (45)Ca2+ uptake via NCX1 (IC50 =
      2.9 microM) than to that via NCX2 or NCX3. Our chimeric and site-directed
      mutagenesis revealed that Phe-213, Val-227, Tyr-228, Gly-833, and Asn-839 in NCX1
      are molecular determinants for interaction with SN-6. We also found that SN-6
      potently protects against hypoxia/reoxygenation-induced cell damage in renal
      tubular cells.

PMID- 17446498
TI  - Electrophysiological effects of SN-6, a novel Na+/Ca2+ exchange inhibitor on
      membrane currents in guinea pig ventricular myocytes.
AB  - We examined the effect of SN-6 on the Na+/Ca2+ exchanger (NCX) current (I(NCX))
      and other membrane currents in isolated guinea pig ventricular myocytes using the
      whole-cell voltage clamp technique. SN-6 suppressed the bidirectional I(NCX) in a
      concentration-dependent manner. The IC50 values of SN-6 were 2.3 microM and 1.9
      microM for the outward and inward components of the bidirectional I(NCX),
      respectively. On the other hand, SN-6 suppressed the unidirectional outward
      I(NCX) more potently than the inward I(NCX), with an IC(50) value of 0.6 microM.
      SN-6 at 10 microM inhibited the unidirectional inward I(NCX) by only 22.4 +/-
      3.1%. SN-6 suppressed I(NCX) more potentially when intracellular Na+
      concentration became higher. SN-6 inhibited I(Na), I(Ca), I(Kr), I(Ks), and I(K1)
      by about 13%, 34%, 33%, 18%, and 13%, respectively. SN-6 shortened the action
      potential duration (APD) by about 34% and 25% at APD(50) and APD(90),
      respectively. These results indicate that SN-6 inhibits NCX in a similar manner
      to that of KB-R7943. SN-6 and KB-R7943 inhibit the unidirectional outward I(NCX)
      more potently than the unidirectional inward I(NCX). Both drugs inhibit NCX in an
      intracellular Na+ concentration-dependent manner. However, SN-6 affected other
      membrane currents less potently than KB-R7943.

PMID- 17446499
TI  - Directionality in drug action on sodium-calcium exchange.
AB  - In pathological conditions, the exchanger may generate deleterious calcium entry.
      A drug that inhibited calcium entry, while still allowing transport of calcium
      out of the cell would then seem attractive. In fact, this is impossible for
      thermodynamic reasons. Inhibitors may appear to be more effective when the
      exchanger is operating in net calcium entry mode than in calcium exit mode. This
      is, however, always attributable to differences in conditions because there is
      strong internal sodium dependence of drug action on the exchanger. When the
      exchanger is operating near equilibrium, drug action is found to be equally
      effective in both directions.

PMID- 17446500
TI  - Non-arteritic anterior ischaemic optic neuropathy and cataract surgery.

PMID- 17446501
TI  - The use of systemic steroids and photodynamic treatment for choroidal
      neovascularisation in young patients.

PMID- 17446502
TI  - Topical azithromycin: new evidence?

PMID- 17446503
TI  - Decreased prevalence of asymptomatic choroidal metastases in disseminated breast
      and lung cancer: argument against screening.

PMID- 17446504
TI  - Risk of non-arteritic anterior ischaemic optic neuropathy (NAION) after cataract
      extraction in the fellow eye of patients with prior unilateral NAION.
AB  - AIM: To determine the risk of non-arteritic anterior ischaemic optic neuropathy
      (NAION) after cataract extraction (CE) in the fellow eye of patients with prior
      unilateral NAION. DESIGN: Retrospective, cohort study. METHODS: Medical records
      of patients with NAION evaluated in our institution between 1 January 1986 and 31
      December 2001 were reviewed to determine the onset of NAION and the time of CE.
      Patients were excluded if the date of NAION and CE was unreliable, or if CE in
      the fellow eye was performed before the unilateral NAION. Statistical analysis
      was performed by including fellow eye CE as a time-dependent covariate in a Cox
      proportional hazards regression model of NAION incidence in the fellow eye.
      RESULTS: Of the 325 eligible patients, 9 (53%) of 17 patients with NAION who
      underwent CE in the fellow eye developed fellow eye NAION, and 59 (19%) of 308
      patients with NAION who did not undergo CE in the fellow eye developed fellow eye
      NAION. Cataract extraction in the fellow eye increased the risk of NAION
      occurrence in the fellow eye by 3.6-fold (Cox regression, p=0.001). CONCLUSIONS:
      Patients with unilateral NAION are at a significantly higher risk of developing
      NAION in the fellow eye after CE.

PMID- 17446505
TI  - Two-year results of surgical removal of choroidal neovascular membranes related
      to non-age-related macular degeneration.
AB  - PURPOSE: To present the 2-year outcomes of surgical removal of non-age-related
      macular degeneration (AMD)-related choroidal neovascular membranes and to
      evaluate any association between visual outcome and baseline clinical factors.
      METHODS: Retrospective consecutive case series. All patients who had surgery for
      non-AMD-related choroidal neovascularisation (CNV) between November 1997 and
      March 2003 under the care of a single surgeon (WA) were included in the study.
      Baseline data including patient age, duration of subfoveal CNV, preoperative
      visual acuity (VA), lesion size, lesion components and aetiology were collected.
      The primary outcome was VA change with secondary outcomes retinal detachment,
      operative peripheral retinal break formation, CNV recurrence and cataract.
      RESULTS: A total of 52 eyes were included in the study. The aetiology of CNV was:
      punctate inner choridopathy 21 (40%); idiopathic 8 (15%); pathologic myopia 6
      (12%); ocular histoplasmosis syndrome 1 (2%); and other 16 (31%). The mean age of
      patients was 41(range 14-72) years. 24-month follow-up was available for 41 (80%)
      eyes. The mean logMAR equivalent baseline acuity was 1.1 and mean lesion size 1.2
      disc areas. An improvement in VA >1 Snellen line was noted in 26 (63%) eyes,
      whereas 10 (24%) eyes remained the same (within 1 line) and 5 (12%) lost >1 line
      of acuity. Improvement in VA was associated with worse baseline VA (84% for eyes
      with VA <or=6/36 vs 31% for those with VA>6/36, p=0.001). No evidence of
      association between 2-year visual outcome and any other baseline factor under
      study was observed. Peripheral retinal breaks were noted in 5 (10%) eyes at the
      time of surgery, and 3 (5.8%) eyes developed postoperative retinal detachments.
      Persistent/recurrent CNV was noted in 17 (33%) eyes. The median time to
      presentation of CNV in these eyes was 27 (range 2-172) weeks. Five eyes underwent
      cataract surgery during the follow-up period. The mean age of these patients was
      significantly higher than the mean age of those who did not require cataract
      surgery (57 vs 37 years, p=0.014). CONCLUSIONS: Surgical excision of non-AMD
      related CNV resulted in improvement of VA in the majority of eyes. Worse
      presenting acuity was associated with better visual improvements.

PMID- 17446506
TI  - Punch biopsy of iris lesions: a novel technique for obtaining histology samples.
AB  - AIM: To obtain iris biopsy samples of sufficient quality and quantity for
      histopathological analysis using a novel punch biopsy technique. METHODS: Two
      patients underwent iris tumour biopsy at an ocular oncology service. A
      trabeculectomy punch (Kelly Descemet's membrane punch) with a 1.0 mm diameter
      head and a 0.75 mm deep bite was inserted through a clear cornea perforated by a
      SatinSlit 3.2 mm angled slit knife into a viscoelastic-filled anterior chamber.
      The Kelly punch was placed over the lesion and pressed down before the punch was
      made. After obtaining the sample, the Kelly punch was removed from the eye and
      then opened over a dry cellulose sponge. Tissue samples were placed in 4%
      formalin and processed routinely for standard staining with H&E, periodic acid
      Schiff and immunostains. RESULTS: In both patients, by using the punch biopsy
      technique with the Kelly punch, we were able to obtain a 0.8 x 0.6 mm piece of
      tissue, large enough for any histological analysis. H&E staining showed spindle
      cell melanoma. Tissue sections, stained positive with MART-1 (melanoma antigen
      recognised by T cells) and negative with cytokeratin, established the diagnosis
      of melanoma of the iris in each of these patients. CONCLUSIONS: Iris biopsy with
      the punch technique yields a tissue biopsy specimen, as opposed to cytology
      samples obtained by fine needle aspiration biopsy. This technique is quick,
      simple to perform and requires non-expensive and easily available equipment. The
      tissue obtained is of sufficient quality and quantity to enable routine and
      special stainings.

PMID- 17446508
TI  - Cyclodiode treatment of neovascular glaucoma secondary to Coats' disease.

PMID- 17446509
TI  - Drug-induced cicatrising granulomatous conjunctivitis.

PMID- 17446507
TI  - A chronic grey matter penumbra, lateral microvascular intussusception and venous
      peduncular avulsion underlie diabetic vitreous haemorrhage.
AB  - The landmark publications that gave such impetus to our understanding of
      proliferative diabetic retinopathy are reviewed in the light of more recent
      reports. Briefly, confluence of small areas of capillary closure in the
      midperipheral and peripheral retina results in arteriovenous shunting and
      abnormal oxygen partial pressure gradients. These gradients embrace a chronic
      ischaemic penumbra that stimulates neuroglial secretion of angiogenic growth
      factors and upregulation of their receptors in the retinal venous endothelium and
      adventitia. The blood shunting produces biomechanical stresses within the veins
      and induces microvascular intussusception near arteriovenous crossings, giving
      way to neovascular outgrowths and/or segmental venous lesions (such as omega
      loops and coils) that penetrate the inner limiting lamina. The lamellar
      collagenous matrix of the vitreous cortex is then exploited for integrin
      dependent rete expansion along chemotactic gradients. During posterior vitreous
      detachment, haemorrhaging takes place from the arterialised veins as venous
      neovascular peduncles are avulsed.

PMID- 17446510
TI  - Clostridium novyi keratitis.

PMID- 17446511
TI  - Orbital mesenchymal hamartoma with rhabdomyomatous features.

PMID- 17446512
TI  - Ecstasy induced acute bilateral angle closure and transient myopia.

PMID- 17446513
TI  - Ophthalmomyiasis externa caused by Dermatobia hominis in Florida.

PMID- 17446514
TI  - Mitochondrial myopathy presenting with segmental corneal oedema and retrocorneal
      membrane.

PMID- 17446515
TI  - Progressive macular thinning after indirect traumatic optic neuropathy documented
      by optical coherence tomography.

PMID- 17446516
TI  - Importance of multimedia visual information in improving patient understanding of
      cataract surgery.

PMID- 17446517
TI  - Evidence for retinal remodelling in retinitis pigmentosa caused by PDE6B
      mutation.

PMID- 17446518
TI  - Severe diffuse lamellar keratitis after femtosecond lamellar keratectomy.

PMID- 17446519
TI  - Changes in the retinal inner limiting membrane associated with Valsalva
      retinopathy.

PMID- 17446520
TI  - Lemon juice and Candida endophthalmitis in crack-cocaine misuse.

PMID- 17446521
TI  - Uterine leiomyomas: MR imaging-guided focused ultrasound surgery--results of
      different treatment protocols.
AB  - PURPOSE: To prospectively assess patient response (after 12 months) to magnetic
      resonance (MR) imaging-guided focused ultrasound surgery in treatment of uterine
      leiomyomas by using two treatment protocols. MATERIALS AND METHODS: This
      prospective clinical trial was approved by institutional review boards and was
      HIPAA compliant. After giving informed consent, patients with symptomatic
      leiomyomas were consecutively enrolled and treated at one of five U.S. centers by
      using an original or a modified protocol. Outcomes were assessed with the symptom
      severity score (SSS) obtained at baseline and 3, 6, and 12 months after
      treatment. Adverse events (AEs) were recorded. Statistical analysis included
      Student t test, Fisher exact test, analysis of covariance, Spearman correlation,
      and logistic regression. RESULTS: One hundred sixty patients had a mean SSS of
      62.1 +/- 16.3 (standard deviation) at baseline, which decreased to 35.5 +/- 19.5
      at 3 months (P<.001) and to 32.3 +/- 19.8 at 6 months (P<.001) and was 32.7 +/-
      21.0 at 12 months (P<.001). Ninety-six patients (mean age, 46.0 years +/- 4.6)
      were treated with an original protocol, and 64 (mean age, 45.9 years +/- 3.9)
      were treated with a modified protocol. Patients in the modified group had a
      significantly greater SSS decrease at 3 months (P=.037) than those in the
      original group, and 73% of those in the original group and 91% of those in the
      modified group reported a significant decrease in SSS (of 10 points or greater)
      at 12 months. No serious AEs were recorded. Fewer AEs were reported in the
      modified group than in the original group (25% vs 13% reporting no event). Of
      evaluable patients, fewer in the modified group chose alternative treatment (28%)
      than in the original group (37%). CONCLUSION: MR imaging-guided focused
      ultrasound surgery results in symptomatic improvement, sustained to 12 months
      after treatment. Treatment with a modified protocol results in greater clinical
      effectiveness and fewer AEs.

PMID- 17446522
TI  - Granulocytic sarcoma of bowel: CT findings.
AB  - PURPOSE: To evaluate retrospectively the computed tomographic (CT) findings of
      granulocytic sarcoma of the bowel. MATERIALS AND METHODS: The institutional
      review boards of all participating institutions approved this study and waived
      the requirement for informed consent. CT scans were retrospectively reviewed in
      eight patients (seven men, one woman; age range, 23-71 years; mean age, 46 years)
      with pathologically proved granulocytic sarcoma of the small and/or large bowel.
      CT findings were evaluated with regard to the sites, morphologic characteristics,
      and contrast material enhancement patterns of the lesions, along with other
      ancillary findings (ie, peritoneal and mesenteric infiltration, ascites,
      lymphadenopathy, bowel perforation, and obstruction). RESULTS: Eight patients had
      a total of 13 lesions in the bowel (of which eight were pathologically proved),
      involving the duodenum (n=1), jejunum (n=2), ileum (n=5), sigmoid colon (n=1),
      and rectum (n=4); multifocal bowel lesions were noted in four patients. The
      lesion varied in shape, with wall thickening alone in three of 13 lesions, an
      intraluminal polypoid mass in four, an exophytic mass in one, and a combination
      of findings in five. Contrast material enhancement, relative to the back
      musculature, showed isoattenuation in seven lesions, hyperattenuation in four,
      and hypoattenuation in two. Five of eight patients had multiple peritoneal masses
      with diffuse mesenteric or peritoneal infiltration. Ascites was present in six of
      eight patients; lymphadenopathy (especially in the mesentery), in five; bowel
      perforation, in two; and bowel obstruction, in one. CONCLUSION: Granulocytic
      sarcoma of the bowel is characterized by variability in shape and contrast
      enhancement and has a high predilection for mesenteric and peritoneal spread.

PMID- 17446523
TI  - High-spatial-resolution contrast-enhanced MR angiography of the intracranial
      venous system with fourfold accelerated two-dimensional sensitivity encoding.
AB  - Informed consent was obtained; the study was HIPAA compliant and institutional
      review board approved. Fourfold accelerated (FFA) two-dimensional (2D)
      sensitivity encoding (SENSE) (65 seconds) was prospectively compared with its
      nonaccelerated counterpart (4 minutes 20 seconds) for diagnostic image quality
      and sharpness of visualization of blood vessels at 1.5 T with three-dimensional
      (3D) intracranial contrast-enhanced magnetic resonance venography in 18
      consecutive volunteers (10 men, eight women; mean age, 48.4 years) and two
      patients (55-year-old man, 30-year-old woman). Two readers compared FFA 2D SENSE
      results with results from its nonaccelerated counterpart; they rated
      visualization of large and medium sinuses as equivalent (P>.1) and that of small
      deep cerebral veins (P<.01) and superficial cerebral veins (P<.001) as superior.
      Overall diagnostic image quality ratings were excellent for 62% and 80% of
      nonaccelerated and FFA 2D SENSE results, respectively (P<.05). FFA 2D SENSE may
      become the method of choice for fast visualization of intracranial venous
      vasculature in clinical practice.

PMID- 17446524
TI  - Contrast-enhanced MR mammography for evaluation of the contralateral breast in
      patients with diagnosed unilateral breast cancer or high-risk lesions.
AB  - PURPOSE: To prospectively evaluate accuracy of gadobenate dimeglumine-enhanced
      magnetic resonance (MR) mammography for depiction of synchronous contralateral
      breast cancer in patients with newly diagnosed unilateral breast cancer or high
      risk lesions, with histologic analysis or follow-up as reference. MATERIALS AND
      METHODS: The study had ethics committee approval; all patients provided written
      informed consent. One hundred eighteen consecutive women (mean age, 52 years)
      with unilateral breast cancer or high-risk lesions and negative findings in the
      contralateral breast at physical examination, ultrasonography, and conventional
      mammography underwent gadobenate dimeglumine-enhanced 1.5-T MR mammography.
      Transverse three-dimensional T1-weighted gradient-echo images were acquired
      before and at 0, 2, 4, 6, and 8 minutes after gadobenate dimeglumine
      administration (0.1 mmol per kilogram body weight). Breast Imaging Reporting and
      Data System (BI-RADS) was used to categorize breast density and the level of
      suspicion for malignant contralateral breast lesions. Results were compared with
      histologic findings. Sensitivity, specificity, accuracy, and positive and
      negative predictive values for contrast-enhanced MR mammography were evaluated.
      RESULTS: Contrast-enhanced MR mammography revealed contralateral lesions in 28
      (24%) of 118 patients. Twenty-four lesions were detected in patients with dense
      breasts (BI-RADS breast density category III or IV). Lesions in eight (29%) of 28
      patients were BI-RADS category 4; patients underwent biopsy. Lesions in 20 (71%)
      patients were BI-RADS category 5; patients underwent surgery. At histologic
      analysis, 22 lesions were confirmed as malignant; six lesions were fibroadenomas.
      No false-negative lesions were detected; none of the fibroadenomas were BI-RADS
      category 5. The sensitivity, specificity, accuracy, and positive and negative
      predictive values of contrast-enhanced MR mammography for depiction of malignant
      or high-risk contralateral lesions were 100%, 94%, 95%, 79%, and 100%,
      respectively. Follow-up findings (12-24 months) confirmed absence of
      contralateral lesions in 90 of 118 patients with negative contrast-enhanced MR
      mammographic findings in the contralateral breast. CONCLUSION: Contrast-enhanced
      MR mammography is accurate for detection of synchronous contralateral cancer or
      high-risk lesions in patients with newly diagnosed breast cancer or high-risk
      lesions.

PMID- 17446525
TI  - Dose performance of a 64-channel dual-source CT scanner.
AB  - PURPOSE: To prospectively compare the dose performance of a 64-channel multi
      detector row computed tomographic (CT) scanner and a 64-channel dual-source CT
      scanner from the same manufacturer. MATERIALS AND METHODS: To minimize dose in
      the cardiac (dual-source) mode, the evaluated dual-source CT system uses a
      cardiac beam-shaping filter, three-dimensional adaptive noise reduction, heart
      rate-dependent pitch, and electrocardiographically based modulation of the tube
      current. Weighted CT dose index per 100 mAs was measured for the head, body, and
      cardiac beam-shaping filters. Kerma-length product was measured in the spiral
      cardiac mode at four pitch values and three electrocardiographic modulation
      temporal windows. Noise was measured in an anthropomorphic phantom. Data were
      compared with data from a 64-channel multi-detector row CT scanner. RESULTS: For
      the multi-detector row and dual-source CT systems, respectively, weighted CT dose
      index per 100 mAs was 14.2 and 12.2 mGy (head CT), 6.8 and 6.4 mGy (body CT), and
      6.8 and 5.3 mGy (cardiac CT). In the spiral cardiac mode (no
      electrocardiographically based tube current modulation, 0.2 pitch), equivalent
      noise occurred at volume CT dose index values of 23.7 and 35.0 mGy (coronary
      artery calcium CT) and 58.9 and 61.2 mGy (coronary CT angiography) for multi
      detector row CT and dual-source CT, respectively. The use of heart rate-dependent
      pitch values reduced volume CT dose index to 46.2 mGy (0.265 pitch), 34.0 mGy
      (0.36 pitch), and 26.6 mGy (0.46 pitch) compared with 61.2 mGy for 0.2 pitch. The
      use of electrocardiographically based tube current-modulation and temporal
      windows of 110, 210, and 310 msec further reduced volume CT dose index to 9.1
      25.1 mGy, dependent on the heart rate. CONCLUSION: For electrocardiographically
      gated coronary CT angiography, image noise equivalent to that of multi-detector
      row CT can be achieved with dual-source CT at doses comparable to or up to a
      factor of two lower than the doses at multi-detector row CT, depending on heart
      rate of the patient.

PMID- 17446526
TI  - Risk of iodinated contrast material--induced nephropathy with intravenous
      administration.

PMID- 17446527
TI  - Essential role of MMP-12 in Fas-induced lung fibrosis.
AB  - Acute lung injury (ALI) is characterized by an early inflammatory response
      followed by a late fibroproliferative phase, and by an increase in the
      bronchoalveolar lavage fluid (BALF) concentrations of bioactive soluble FasL
      (sFasL). Activation of Fas (CD95) has been associated with the development of
      lung fibrosis in mice. The goal of this study was to determine the mechanisms
      that link Fas activation with the development of fibrosis in the lungs. We
      treated mice with three daily intratracheal instillations of a Fas-activating
      monoclonal antibody (Jo2) or a control IgG, and studied the animals at sequential
      times. Mice treated with Jo2 had increased caspase-3 activation in alveolar wall
      cells on Days 2, 4, and 7; an inflammatory response peaking on Day 7, and
      increased total lung collagen on Day 21. Gene expression profiling performed on
      Days 2, 4, and 7 showed sequential activation of co-regulated profibrotic genes,
      including marked up-regulation of matrix metalloproteinase 12 (MMP-12). Targeted
      deletion of MMP-12 protected mice from Fas-induced pulmonary fibrosis, even
      though the inflammatory responses in the lungs were similar to those of wild-type
      mice. Compared with wild-type mice, the mmp12(-/-) mice showed decreased
      expression of the profibrotic genes egr1 and cyr61. We conclude that Fas
      activation in the lungs induces a complex response that includes apoptosis,
      inflammation, and eventually fibrosis, and that MMP-12 is essential for the
      fibrotic phenotype. We speculate that MMP-12 activity is required for activation
      of the profibrotic genes egr1 and cyr61.

PMID- 17446528
TI  - Profibrotic effect of IL-9 overexpression in a model of airway remodeling.
AB  - IL-9 overexpression protects against alveolar fibrosis induced by crystalline
      silica particles. This cytokine is also involved in allergic asthma. In the
      present study, we examined the effect of IL-9 overexpression on the subepithelial
      fibrotic response, a feature of asthmatic remodeling, induced by chronic exposure
      to Alternaria alternata extract. IL-9-overexpressing mice (Tg5) and their wild
      type counterparts (FVB) were intranasally exposed to A. alternata extract or PBS
      (controls) twice a week during 3 mo. At the end of the allergic challenge,
      enhanced pause (Penh) measured in response to methacholine and fibrotic
      parameters, such as collagen and fibronectin lung content, were significantly
      higher in Tg5 compared with FVB. Staining of lung sections with Masson's
      Trichrome also showed more collagen fibers in peribronchial areas of treated Tg5
      mice. A similar recruitment of inflammatory cells was observed in challenged FVB
      and Tg5 mice, except for eosinophils, which were significantly more abundant in
      the lung of Tg5. High serum levels of IgE and IgG1 in both strains indicated that
      FVB and Tg5 developed a strong type 2 immune response. The concentration of the
      eosinophil chemoattractant RANTES and the profibrotic mediator connective tissue
      growth factor (CTGF) was higher in the BAL of challenged Tg5 than FVB. These
      results demonstrate a profibrotic role of IL-9 in an airway remodeling model,
      possibly involving eosinophils and CTGF. These data also highlight a dual role of
      IL-9 in lung fibrosis, being anti- or profibrotic depending on the alveolar or
      airway localization of the process, respectively.

PMID- 17446529
TI  - CD44 regulates macrophage recruitment to the lung in lipopolysaccharide-induced
      airway disease.
AB  - LPS from bacteria is ubiquitous in the environment and can cause airway disease
      and modify allergic asthma. Identification of gene products that modulate the
      biologic response to inhaled LPS will improve our understanding of inflammatory
      airways disease. Previous work has identified quantitative trait loci for the
      response to inhaled LPS on chromosomes 2 and 11. In these regions, 28 genes had
      altered RNA expression after inhalation of LPS, including CD44, which was
      associated with differences in both TNF-alpha levels and neutrophil recruitment
      into the lung. It has previously been shown that CD44 can modulate macrophage
      recruitment in response to Mycobacterium tuberculosis, as well as clearance of
      neutrophils after lung injury with both bleomycin and live Escherichia coli
      bacteria. In this study, we demonstrate that the biologic response to inhaled LPS
      is modified by CD44. Macrophages failed to be recruited to the lungs of CD44
      deficient animals at all time points after LPS exposure. CD44-deficient
      macrophages showed reduced motility in a Transwell migration assay, reduced
      ability to secrete the proinflammatory cytokine TNF-alpha, reduced in vivo
      migration in response to monocyte chemotactic protein-1, and diminished adhesion
      to vascular endothelia in the presence of TNF-alpha. In addition, CD44-deficient
      animals had 150% fewer neutrophils at 24 h and 50% greater neutrophils 48 h after
      LPS exposure. These results support the role of CD44 in modulating the biologic
      response to inhaled LPS.

PMID- 17446530
TI  - Methionine aminopeptidase-2 as a selective target of myofibroblasts in pulmonary
      fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive, scarring lung disease
      characterized by fibroblast accumulation and deposition of collagen. Factors that
      promote growth and/or survival of fibroblasts are potential therapeutic targets.
      Methionine aminopeptidase 2 (MetAP2), a member of the aminopeptidase family of
      proteases, has been implicated in cell proliferation in a variety of cell types,
      but its expression and function in the lung is not known. By
      immunohistochemistry, MetAP2 was expressed in many cell types, including
      fibroblasts, in IPF lungs. Fumagillin, an irreversible inhibitor of the enzymatic
      activity of MetAP2, attenuated collagen deposition in the bleomycin model of
      acute lung injury in mice. Treatment with fumagillin caused a selective reduction
      in the numbers of bromodeoxyuridine (BrdU)-positive myofibroblasts, but not type
      II alveolar epithelial cells, macrophages, or B- and T-lymphocytes in the lungs
      of bleomycin-treated mice. Incubation of primary rat lung fibroblasts with either
      fumagillin or with short interfering RNA that targeted MetAP2 led to reduced
      proliferation, as assessed by incorporation of BrdU. The profibrotic growth
      factor, platelet-derived growth factor, increased expression of MetAP2 in rat
      lung fibroblasts. We propose that MetAP2 plays a role in the proliferation of
      fibroblasts and myofibroblasts in fibrotic lung diseases and may serve as a novel
      pharmacologic target in IPF.

PMID- 17446531
TI  - Use of maternal GHb concentration to estimate the risk of congenital anomalies in
      the offspring of women with prepregnancy diabetes.
AB  - OBJECTIVE: We sought to determine the absolute risk of having a congenital
      anomaly in relation to periconceptional GHb concentration among women with
      prepregnancy diabetes. RESEARCH DESIGN AND METHODS: Two reviewers independently
      retrieved all cohort studies through a systematic literature search between
      January 1985 and May 2006. For each study, the absolute risk of having a
      pregnancy affected by a major or minor structural anomaly (diagnosed either
      antenatally or up to 28 days after conception) was calculated according to the
      number of SDs of GHb above the mean for nondiabetic, nonpregnant control
      subjects. A multilevel logistic-normal model was used to pool the data, which
      were expressed in tabular and graphic formats. RESULTS: In seven cohort studies,
      there were 117 anomalies among 1,977 pregnancies. At a periconceptional GHb
      concentration 0 SD above normal, the absolute risk of a pregnancy affected by a
      congenital anomaly was approximately 2% (95% CI 0.0-4.4). At 2 SD above normal,
      the risk was 3% (0.4-6.1), and at 8 SD it was approximately 10% (2.3-17.8). For
      each 1-SD unit increase in GHb, the associated risk of a congenital malformation
      increased by an odds ratio of 1.2 (95% CI 1.1-1.4). The risk in relation to A1C
      followed the same pattern. CONCLUSIONS: Using data from a limited number of
      published studies, a practical aid was developed to optimize use of the GHb and
      A1C concentrations for estimating the absolute risk of a congenital anomaly in
      the offspring of women with prepregnancy diabetes.

PMID- 17446532
TI  - Paradoxical relationships between anthropometric variables and phenotypic
      expression of the metabolic syndrome in nondiabetic Polynesians of New Caledonia.

PMID- 17446533
TI  - Hyperglycemia is a major determinant of albumin permeability in diabetic
      microcirculation: the role of mu-calpain.
AB  - Increased permeability to albumin is a well-known feature of diabetic
      microvasculature and a negative prognostic factor of vascular complications. The
      mechanisms responsible for loss of the physiological albumin barrier in diabetic
      organs remain only partially understood. We have recently demonstrated that the
      protease mu-calpain is activated in hyperglycemia, which causes endothelial
      dysfunction and vascular inflammation. In the present study, we investigated
      whether mu-calpain is involved in the hyperpermeability of the diabetic
      vasculature. We also investigated the mechanistic roles of hyperglycemia and
      leukocyte adhesion in this process. Albumin permeability in the intact
      microcirculation of the Zucker diabetic fatty (ZDF) rat was quantified by
      intravital microscopy. Extravasation of albumin in the microcirculation of ZDF
      rats was significantly increased when compared with nondiabetic Zucker lean (ZL)
      rats. Microvascular albumin leakage was prevented by either antisense depletion
      of mu-calpain or pharmacological inhibition of calpain in vivo. Calpain
      inhibition also attenuated urinary albumin excretion in ZDF rats. Glucose
      concentrations in the range of those found in the blood of ZDF rats increased
      albumin permeability in nondiabetic ZL rats. Thus, this demonstrates a
      mechanistic role for hyperglycemia in the hypermeability of diabetes. Depletion
      of polymorphonuclear leukocytes in vivo failed to prevent glucose-induced
      hypermeability, which suggests that hyperglycemia can disrupt the physiological
      endothelial cell barrier of the microcirculation, even in the absence of
      increased overt leukocyte-endothelium interactions.

PMID- 17446534
TI  - Effects of the renin-angiotensin system genes and salt sensitivity genes on blood
      pressure and atherosclerosis in the total population and patients with type 2
      diabetes.
AB  - Most studies on the genetic determinants of blood pressure and vascular
      complications of type 2 diabetes have focused on the effects of single genes.
      These studies often have yielded conflicting results. Therefore, we examined the
      combined effects of three renin-angiotensin system (RAS) genes and three salt
      sensitivity genes in relation to blood pressure and atherosclerosis in the total
      population and type 2 diabetic patients. The study was a part of the Rotterdam
      Study, a population-based cohort study. We have genotyped three RAS gene
      polymorphisms and three salt sensitivity gene polymorphisms. Diabetic patients
      with three risk genotypes of the RAS genes had a 6.9 mmHg higher systolic blood
      pressure (P for trend = 0.04) and a 6.0 mmHg higher pulse pressure (P for trend =
      0.03) than those who did not carry any risk genotypes. Diabetic patients with
      three risk genotypes of the salt sensitivity genes had a 9.0 mmHg higher systolic
      blood pressure (P = 0.19) and a 13.1 mmHg higher pulse pressure (P = 0.02).
      Diabetic patients who carried three risk genotypes for the RAS genes had a higher
      mean intima-media thickness than those with two risk genotypes (mean difference
      0.04 mm, P = 0.02). We found that among type 2 diabetic patients, mean systolic
      blood pressure, pulse pressure, and risk of hypertension increased with the
      number of risk genotypes for the RAS genes and the salt sensitivity genes.

PMID- 17446535
TI  - Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and
      permanent diabetes in childhood or adulthood.
AB  - Transient neonatal diabetes mellitus (TNDM) is diagnosed in the first 6 months of
      life, with remission in infancy or early childhood. For approximately 50% of
      patients, their diabetes will relapse in later life. The majority of cases result
      from anomalies of the imprinted region on chromosome 6q24, and 14 patients with
      ATP-sensitive K+ channel (K(ATP) channel) gene mutations have been reported. We
      determined the 6q24 status in 97 patients with TNDM. In patients in whom no
      abnormality was identified, the KCNJ11 gene and/or ABCC8 gene, which encode the
      Kir6.2 and SUR1 subunits of the pancreatic beta-cell K(ATP) channel, were
      sequenced. K(ATP) channel mutations were found in 25 of 97 (26%) TNDM probands
      (12 KCNJ11 and 13 ABCC8), while 69 of 97 (71%) had chromosome 6q24 abnormalities.
      The phenotype associated with KCNJ11 and ABCC8 mutations was similar but markedly
      different from 6q24 patients who had a lower birth weight and who were diagnosed
      and remitted earlier (all P < 0.001). K(ATP) channel mutations were identified in
      26 additional family members, 17 of whom had diabetes. Of 42 diabetic patients,
      91% diagnosed before 6 months remitted, but those diagnosed after 6 months had
      permanent diabetes (P < 0.0001). K(ATP) channel mutations account for 89% of
      patients with non-6q24 TNDM and result in a discrete clinical subtype that
      includes biphasic diabetes that can be treated with sulfonylureas. Remitting
      neonatal diabetes was observed in two of three mutation carriers, and permanent
      diabetes occurred after 6 months of age in subjects without an initial diagnosis
      of neonatal diabetes.

PMID- 17446536
TI  - Viscosity-dependent protein dynamics.
AB  - Spectrally resolved stimulated vibrational echo spectroscopy is used to
      investigate the dependence of fast protein dynamics on bulk solution viscosity at
      room temperature in four heme proteins: hemoglobin, myoglobin, a myoglobin mutant
      with the distal histidine replaced by a valine (H64V), and a cytochrome c552
      mutant with the distal methionine replaced by an alanine (M61A). Fructose is
      added to increase the viscosity of the aqueous protein solutions over many orders
      of magnitude. The fast dynamics of the four globular proteins were found to be
      sensitive to solution viscosity and asymptotically approached the dynamical
      behavior that was previously observed in room temperature sugar glasses. The
      viscosity-dependent protein dynamics are analyzed in the context of a
      viscoelastic relaxation model that treats the protein as a deformable breathing
      sphere. The viscoelastic model is in qualitative agreement with the experimental
      data but does not capture sufficient system detail to offer a quantitative
      description of the underlying fluctuation amplitudes and relaxation rates. A
      calibration method based on the near-infrared spectrum of water overtones was
      constructed to accurately determine the viscosity of small volumes of protein
      solutions.

PMID- 17446537
TI  - Partial splenic embolization in the treatment of patients with portal
      hypertension: a review of the english language literature.
AB  - This article reviews the existing literature on the use of partial splenic
      embolization in patients with portal hypertension. All articles published in the
      English language on splenic embolization or partial splenic embolization as a
      treatment for portal hypertension were identified with a PubMed search from 1973
      through 2005. Partial splenic embolization appears to be efficacious in reducing
      episodes of variceal bleeding, improving hematologic parameters, enhancing
      hepatic protein synthesis, and reducing the severity of hepatic encephalopathy.
      Associated morbidity and mortality appear to be acceptable. The literature,
      however, is limited in quality. Given the potential benefits of partial splenic
      embolization, further investigation is warranted to allow evidence-based
      evaluation of its use.

PMID- 17446538
TI  - Interventional radiology simulation: prepare for a virtual revolution in
      training.
AB  - It is becoming increasingly difficult to learn interventional radiology (IR)
      skills because there are fewer "straightforward" invasive diagnostic imaging
      studies, a reduction in the time available for training, concerns about patient
      safety, and changing patient perceptions. Computer-based simulation has the
      potential to allow an operator to realistically perform a virtual procedure with
      feedback about performance and could remove at least some of the patient's role
      during the learning curve. To do this effectively requires a strategy for
      integrating simulator models into curricula and the development of standards for
      their validation.

PMID- 17446539
TI  - Secondary interventions after elective endovascular repair of degenerative
      thoracic aortic aneurysms: results of the European collaborators registry
      (EUROSTAR).
AB  - PURPOSE: The need for secondary interventions is an important indicator of
      intermediate and long-term success of endovascular repair of degenerative
      thoracic aortic aneurysm. The purpose of this study was to analyze the occurrence
      and consequences of secondary procedures. MATERIALS AND METHODS: Data from 213
      patients electively subject to operation for degenerative thoracic aortic
      aneurysm and achieving primary success and who were enrolled in the EUROSTAR
      registry were analyzed. Secondary procedures were categorized as follows:
      transfemoral endovascular reintervention, extraanatomic secondary procedures, and
      transthoracic surgery. RESULTS: Overall, 25 (12%) of the patients with an
      elective treatment for a degenerative thoracic aneurysm had secondary
      intervention, occurring at a mean of 8 months after the initial procedure.
      Seventeen (68%) of the secondary interventions were via a transfemoral approach,
      six (24%) involved a transthoracic procedure, and two (8%) involved extraanatomic
      bypass. The cumulative percentage of freedom from intervention at 1 and 2 years
      was 86% and 83%, respectively. Endoleak (relative risk, 5.21) was the most
      frequent cause for secondary transfemoral intervention. For the other secondary
      interventions, no principal indication for reintervention could be identified.
      Patients who needed secondary interventions more frequently suffered from
      preoperative back pain (20% vs 44%, P = .008), and their thoracic aneurysms had a
      longer length (mean, 95.6 mm vs 133.2 mm, P = .006). The 2-year cumulative
      survival rate of patients without secondary intervention was 85% compared with
      58% in the patients who received secondary intervention (P = .0001). CONCLUSIONS:
      Regular surveillance after endovascular degenerative thoracic aneurysm repair is
      needed as secondary interventions were required throughout the follow-up period.

PMID- 17446540
TI  - Diagnosis of aortoenteric fistulas with CT angiography.
AB  - PURPOSE: To describe the diagnostic findings of primary and secondary
      aortoenteric fistulas (AEFs) at computed tomographic (CT) angiography in a cohort
      of patients known to have AEF and to correlate those findings with those from
      endoscopic gastroduodenoscopy (EGD) and surgery. MATERIALS AND METHODS: CT
      angiography was performed in nine patients with AEF. There were four men and five
      women aged 43-85 years (mean age, 67 years). All CT angiograms were
      retrospectively reviewed for signs of AEF. Reports from EGD, surgery, and
      pathologic examination were also reviewed. RESULTS: One patient had a primary
      AEF, and eight patients had a secondary AEF. Findings at CT angiography were
      suggestive of the diagnosis in all nine patients. The two definitive CT
      angiographic findings were identification of the graft within the bowel lumen in
      two patients (22%) and active extravasation in one patient (11%), allowing the
      definitive diagnosis in three of the nine patients (33%). Secondary signs, which
      helped predict the high likelihood of the diagnosis but could also be seen in
      graft infection or inflammation without AEF, were as follows (in descending order
      of frequency): effacement of the periaortic or perigraft fat plane and the fat
      plane between the aorta and bowel (nine patients, 100%), perigraft soft tissue
      (nine patients, 100%), bowel wall thickening adjacent to the graft (eight
      patients, 89%), perigraft fluid (seven patients, 78%), perigraft hematoma (six
      patients, 67%), pseudoaneurysm or aneurysm bulge (six patients, 67%), ectopic gas
      (five patients, 56%), and dystrophic vascular graft calcification (one patient,
      11%). The diagnosis was confirmed surgically in seven patients and with clinical
      follow-up in two. CONCLUSION: CT angiography is well suited for helping make or
      suggesting the diagnosis of AEF and is potentially more accurate than EGD.

PMID- 17446541
TI  - Clinical comparison of two optional vena cava filters.
AB  - PURPOSE: To compare the clinical safety and efficiency of two optional inferior
      vena cava (IVC) filters. MATERIAL AND METHODS: Ninety-three consecutive Gunther
      Tulip filters (92 patients) were compared with 83 consecutive OptEase filters (80
      patients). Filters were placed at the same institution in patients with high-risk
      multiple trauma or those undergoing neurosurgery with contraindications to
      primary prophylaxis (70 patients in the Gunther Tulip group and 44 in the OptEase
      group) and in patients with venous thromboembolism and contraindications to
      anticoagulation (22 patients in the Gunther Tulip group and 36 in the OptEase
      group). The filters were placed in an angiography suite. Catheter vena cavography
      was performed before filter placement and intended retrieval. Permanent filters
      were followed-up with duplex ultrasonography and conventional radiography.
      RESULTS: All filters were inserted infrarenally without any complications.
      Fluoroscopy times for placement and retrieval were longer for the Gunther Tulip
      group than the OptEase group. The mean dwelling time was 11 days (range, 3-27
      days) for the Gunther Tulip filters and 13.8 days (range, 1-34 days) for the
      OptEase filters. No symptomatic pulmonary emboli (PE) occurred in patients with
      intended temporary filtration while the devices were in place. Forty-six of the
      93 Gunther Tulip filters (49%) and 58 of the 83 OptEase filters (70%) were
      removed. Two Gunther Tulip filters could not be retrieved for technical reasons.
      The mean follow-up for the permanent Gunther Tulip (n = 19) and OptEase (n = 8)
      filters was 41 and 7 months, respectively. One patient from each group had late
      caval thrombosis. There were no cases of filter migration or disintegration.
      CONCLUSION: Both optional IVC filters are safe and seem to prevent symptomatic
      PE. On the basis of the fluoroscopy times, the OptEase filters appear to be more
      operator-friendly. Late filter-associated complications are rare with these
      filter designs.

PMID- 17446542
TI  - Analysis of tip malposition and correction in peripherally inserted central
      catheters placed at bedside by a dedicated nursing team.
AB  - PURPOSE: To analyze the patterns of postplacement tip malposition in peripherally
      inserted central catheters (PICCs) placed at bedside, and to describe results of
      bedside and imaging-guided correction of tip malposition. MATERIALS AND METHODS:
      With use of a quality assurance database, all episodes of tip malposition in
      PICCs placed at bedside were reviewed. Catheter tip location, success or failure
      of bedside repositioning (in a subset of patients, by using over-the-wire
      techniques), findings in the interventional radiology (IR) division, and tip
      correction method used in the IR suite (repositioning vs replacement) were
      determined with a review of medical records. RESULTS: During the 18-month study
      period, 2,367 attempts were made to place a PICC at bedside; 1,654 attempts (70%)
      were initially successful. Of these, 163 tips (10%) were malpositioned. Complete
      records for 132 malpositioned tips were available for analysis. Malpositioned
      tips were located in the ipsilateral internal jugular vein in 45 of the 132 cases
      (36%), axillary vein in 36 cases (27%), ipsilateral subclavian vein in 25 cases
      (19%), ipsilateral brachiocephalic vein in 15 cases (11%), contralateral
      subclavian vein in four cases (3%), contralateral brachiocephalic vein in two
      cases (2%), contralateral internal jugular vein in one case (1%), and subclavian
      tributary in one case (1%). In three cases (2%), the tip was coiled in the
      superior vena cava. Malposition was corrected with catheter exchange in 76 of the
      132 cases (58%), repositioning in 48 cases (36%), or removal in one case (1%).
      Spontaneous correction occurred in seven of the 132 malpositioned tips (5%). One
      hundred nine tips (83%) were repositioned in the IR division with use of imaging
      guidance, with 100% success. Twenty-five attempts were made to correct
      malposition at bedside; 16 of those attempts (64%) were successful. CONCLUSION:
      Tip malposition is relatively frequent with bedside placement of PICCs.
      Preliminary data suggest that most malpositions can be corrected with bedside
      techniques. Spontaneous correction may occur but is relatively uncommon.

PMID- 17446543
TI  - Efficacy of mitomycin C irrigation after removal of an occluded nasolacrimal
      stent.
AB  - PURPOSE: Mitomycin C (MMC) acts as a potent fibroblastic inhibitor, and topical
      application of MMC is effective in preventing scar formation. The purpose of this
      study was to evaluate the safety and efficacy of MMC irrigation after removal of
      an occluded nasolacrimal stent from the lacrimal system. MATERIALS AND METHODS: A
      total of 57 lacrimal systems after removal of an occluded stent were assigned to
      one of two groups: 23 lacrimal systems were irrigated with MMC after stent
      removal (MMC group), and 34 lacrimal systems were not irrigated with MMC after
      stent removal (non-MMC group). In the MMC group, the lacrimal systems were
      irrigated with 0.2 mg/mL MMC through the inferior lacrimal punctum for 3 minutes
      in three different sessions: immediately, 1 week, and 1 month after stent
      removal. The mean and cumulative patency rates after stent removal were
      calculated using the Kaplan-Meier method and were compared between the two groups
      using the log-rank test. RESULTS: Stent removal and MMC irrigation were
      technically successful in all lacrimal systems. There were no side effects or
      complications associated with MMC use. The mean patency rate after stent removal
      was higher in the MMC group than that of the non-MMC group: 10.5 months (95% CI:
      7.04, 13.91) versus 4.5 months (95% CI: 2.40, 6.63), respectively. There was a
      statistically significant difference in the cumulative patency rates after stent
      removal between the two groups (P = .005, log-rank test). CONCLUSIONS: Mitomycin
      C irrigation is safe and effective in increasing patency rate of lacrimal systems
      after removal of an occluded nasolacrimal stent.

PMID- 17446544
TI  - Evaluation of three polytetrafluoroethylene stent-grafts in a model of neointimal
      hyperplasia.
AB  - PURPOSE: The authors tested three different porosities of expanded
      polytetrafluoroethylene (ePTFE)-covered stents and bare stents by using an animal
      model of restenosis. MATERIALS AND METHODS: Both iliac arteries in 18 female pigs
      were injured by overdilating 20-mm-long angioplasty balloons. A 40-mm-long bare
      stent or one of three 44-mm-long ePTFE-covered stents was deployed at the injury
      site. To determine restenosis, neointimal area measurements were made with
      intravascular ultrasonography. Histologic analyses were performed at an
      independent laboratory to determine neointimal attachment. RESULTS: Neointimal
      area was greatest at the middle of the bare stent, where balloon injury was
      centered. When the middle location of the covered stents was evaluated, the
      neointimal area of both the medium- and high-porosity covered stents was smaller
      than that of the matched control stents (P = .0018 and P = .0118, respectively).
      The neointimal area of the low-porosity covered stents was similar to that of the
      bare stents. Histologic study showed dehiscence of the neointima of the low
      porosity covered stents. CONCLUSIONS: The microstructure of the low-porosity
      covered stents did not provide a suitable surface for neointimal attachment and
      did not reduce neointimal growth compared to that with the control stents. The
      microstructure of the medium- and high-porosity covered stents yielded less
      neointimal growth than both the control stents and the low-porosity covered
      stents without evidence of neointimal dehiscence. The authors believe that
      covered stents made with ePTFE with either medium or high porosity could limit
      restenosis in humans compared to that with bare stents.

PMID- 17446545
TI  - Analysis of simulated angiographic procedures. Part 2: extracting efficiency data
      from audio and video recordings.
AB  - PURPOSE: To create and test methods of extracting efficiency data from recordings
      of simulated renal stent procedures. MATERIALS AND METHODS: Task analysis was
      performed and used to design a standardized testing protocol. Five experienced
      angiographers then performed 16 renal stent simulations using the Simbionix
      AngioMentor angiographic simulator. Audio and video recordings of these
      simulations were captured from multiple vantage points. The recordings were
      synchronized and compiled. A series of efficiency metrics (procedure time,
      contrast volume, and tool use) were then extracted from the recordings. The
      intraobserver and interobserver variability of these individual metrics was also
      assessed. The metrics were converted to costs and aggregated to determine the
      fixed and variable costs of a procedure segment or the entire procedure. RESULTS:
      Task analysis and pilot testing led to a standardized testing protocol suitable
      for performance assessment. Task analysis also identified seven checkpoints that
      divided the renal stent simulations into six segments. Efficiency metrics for
      these different segments were extracted from the recordings and showed excellent
      intra- and interobserver correlations. Analysis of the individual and aggregated
      efficiency metrics demonstrated large differences between segments as well as
      between different angiographers. These differences persisted when efficiency was
      expressed as either total or variable costs. CONCLUSIONS: Task analysis
      facilitated both protocol development and data analysis. Efficiency metrics were
      readily extracted from recordings of simulated procedures. Aggregating the
      metrics and dividing the procedure into segments revealed potential insights that
      could be easily overlooked because the simulator currently does not attempt to
      aggregate the metrics and only provides data derived from the entire procedure.
      The data indicate that analysis of simulated angiographic procedures will be a
      powerful method of assessing performance in interventional radiology.

PMID- 17446546
TI  - Magnetic guide-wire navigation in pulmonary and systemic arterial
      catheterization: initial experience in pigs.
AB  - PURPOSE: Cardiovascular catheterization can be challenging whenever a stenosis or
      an abnormal vascular course interferes with probing the target vessel. This study
      addresses the feasibility of navigating a guide wire with a magnetic tip by an
      external magnetic field through pulmonary and systemic arteries in an
      experimental porcine model. MATERIALS AND METHODS: We investigated six piglets
      using magnetic guide-wire navigation. Two pulmonary arteriograms were taken from
      different angles in order to reconstruct the three-dimensional vessel anatomy. A
      computer interface then calculated three-dimensional coordinates for the vessel
      in space. Using these coordinates, two external magnets were positioned to create
      magnetic vectors along the expected vessel course. Magnetically enabled guide
      wires were then navigated into the vessels using the magnetic field to orient the
      guide-wire tips. Aortic and renal branches were addressed in a similar fashion.
      Difficulty in reaching the target vessel was reflected by the number of attempts
      that were necessary. After 10 failed attempts, the maneuver was recorded to have
      failed. RESULTS: Thirty-five of 37 (94.6%) arteries with branches at acute angles
      were reached successfully using magnetic navigation. In two pigs, the left upper
      lobe artery could not be probed. Peripheral arteries of small diameter were
      easier to reach than large central arteries, requiring less attempts.
      CONCLUSIONS: Magnetic guide-wire navigation is feasible in the arteries of the
      lungs, the head and neck, and the kidneys. It is particularly useful in entering
      small arterial branches at acute angles and may facilitate interventional therapy
      in a variety of vascular diseases in children and adults.

PMID- 17446547
TI  - Gastrointestinal complications associated with hepatic arterial Yttrium-90
      microsphere therapy.
AB  - Hepatic arterial therapy with yttrium-90 microspheres exploits the avenue
      provided by the neoplastic microvasculature to deliver high-energy, low
      penetrating therapeutic doses of radiation. Variant hepatic arterial anatomy,
      collateral vessels, and changes in flow dynamics during treatment can affect
      particle dispersion and lead to nontarget particle distribution and subsequent
      gastrointestinal morbidity. Awareness of these variances and techniques to
      prevent gastrointestinal tract microsphere delivery is essential in mitigating
      this serious complication. Our aim is to increase the understanding of the role
      of various imaging and preventative techniques in minimizing this undesired
      effect.

PMID- 17446548
TI  - A novel endovascular adjustable polytetrafluoroethylene-covered stent for the
      management of hepatic encephalopathy after transjugular intrahepatic
      portosystemic shunt.
AB  - Transjugular intrahepatic portosystemic shunt (TIPS) is frequently complicated by
      hepatic encephalopathy. When medical therapy fails, TIPS narrowing and resultant
      increase in the portosystemic pressure gradient and blood flow to the liver is
      performed in order to reverse the encephalopathy. We present a method for
      reducing the TIPS using a polytetrafluoroethylene-covered balloon expandable
      stent placed over a self-expanding stent. This results in a narrowed TIPS that
      not only rapidly increases the portosystemic gradient but also can be adjusted by
      dilating the balloon expandable stent. This method was successful in narrowing
      the patient's TIPS, acutely increasing the portosystemic gradient and reversing
      the hepatic encephalopathy.

PMID- 17446549
TI  - Portal hypertension and obstructive jaundice after hepatic interventions: report
      of two unusual complications.
AB  - We report two unusual complications after a transjugular intrahepatic
      portosystemic shunt and a biliary stent placement, respectively. One patient with
      cirrhosis and portal hypertension developed obstructive jaundice secondary to
      compression of the right hepatic duct by a stent graft placed in the transjugular
      intrahepatic portosystemic shunt. In another patient, biliary stents caused
      obstruction of the portal vein, resulting in symptomatic portal hypertension. An
      awareness of these possible complications is important for early diagnosis and
      appropriate treatment of such complications.

PMID- 17446550
TI  - Patient radiation exposure during uterine fibroid embolization and the dose
      attributable to aortography.
AB  - The techniques used for uterine fibroid embolization (UFE) have rapidly evolved
      during the past decade. One source of uncertainty in the UFE technique has been
      the importance of the contribution of the ovarian artery to the blood supply of
      the uterus and fibroids. Although conventional aortography is often used after
      embolization to assess for collateral arterial supply, few patients are
      identified with sufficient collateral vessels to warrant supplemental
      embolization. One potential downside of routine aortography is the additional
      radiation dose. In this study, the radiation dose associated with UFE and the
      contribution of each component of the procedure to this dose were evaluated, with
      the specific goal of identifying the contribution from aortography. Although the
      overall radiation dose associated with UFE is moderate, aortography contributes a
      substantial amount of additional radiation, more than 20% of the total, which,
      coupled with its low clinical utility, suggests that the routine use of
      aortography at the conclusion of UFE should be reconsidered.

PMID- 17446551
TI  - The use of a picture archiving and communication system to catalogue visible
      light photographic images.
AB  - The purpose of this study was to demonstrate that anatomic visible-light
      photographs can be catalogued using a system primarily intended for viewing
      radiographic images. One hundred four patients from April 2004 through November
      2005 were evaluated for lower extremity venous insufficiency, lower extremity
      varicose veins, and/or telangiectasias. All consultation reports, duplex
      ultrasound reports with images, and lower extremity photographic images were
      archived in the radiology department's picture archiving and communication
      system. The picture archiving and communication system provides an electronic
      alternative to using a conventional, manual, or analog method of storing
      photographic images. Use of a picture archiving and communication system for the
      archiving of photographic images can be a valuable tool for an interventional
      radiologist's vein practice.

PMID- 17446552
TI  - Pseudoaneurysm of a genicular branch of the popliteal artery and deep venous
      thrombosis: an unusual presentation of an osteochondroma.

PMID- 17446553
TI  - Use of a hybrid fluoroscopic/three-dimensional tomographic unit to assist in
      targeting a hepatic metastasis for thermal ablation.

PMID- 17446554
TI  - Polymethylmethacrylate contact dermatitis after vertebroplasty.

PMID- 17446555
TI  - Shotgun protein sequencing: assembly of peptide tandem mass spectra from mixtures
      of modified proteins.
AB  - Despite significant advances in the identification of known proteins, the
      analysis of unknown proteins by MS/MS still remains a challenging open problem.
      Although Klaus Biemann recognized the potential of MS/MS for sequencing of
      unknown proteins in the 1980s, low throughput Edman degradation followed by
      cloning still remains the main method to sequence unknown proteins. The automated
      interpretation of MS/MS spectra has been limited by a focus on individual spectra
      and has not capitalized on the information contained in spectra of overlapping
      peptides. Indeed the powerful shotgun DNA sequencing strategies have not been
      extended to automated protein sequencing. We demonstrate, for the first time, the
      feasibility of automated shotgun protein sequencing of protein mixtures by
      utilizing MS/MS spectra of overlapping and possibly modified peptides generated
      via multiple proteases of different specificities. We validate this approach by
      generating highly accurate de novo reconstructions of multiple regions of various
      proteins in western diamondback rattlesnake venom. We further argue that shotgun
      protein sequencing has the potential to overcome the limitations of current
      protein sequencing approaches and thus catalyze the otherwise impractical
      applications of proteomics methodologies in studies of unknown proteins.

PMID- 17446556
TI  - Proteomics demonstration that normal breast epithelial cells can induce apoptosis
      of breast cancer cells through insulin-like growth factor-binding protein-3 and
      maspin.
AB  - Normal breast epithelial cells are known to exert an apoptotic effect on breast
      cancer cells, resulting in a potential paracrine inhibition of breast tumor
      development. In this study we purified and characterized the apoptosis-inducing
      factors secreted by normal breast epithelial cells. Conditioned medium was
      concentrated by ultrafiltration and separated on reverse phase Sep-Pak C18 and
      HPLC. The proapoptotic activity of eluted fractions was tested on MCF-7 breast
      cancer cells, and nano-LC-nano-ESI-MS/MS allowed the identification of insulin
      like growth factor-binding protein-3 (IGFBP-3) and maspin as the proapoptotic
      factors produced by normal breast epithelial cells. Western blot analysis of
      conditioned media confirmed the specific secretion of IGFBP-3 and maspin by
      normal cells but not by breast cancer cells. Immunodepletion of IGFBP-3 and
      maspin completely abolished the normal cell-induced apoptosis of cancer cells,
      and recombinant proteins reproduced the effect of normal cell-conditioned medium
      on apoptosis of breast cancer cells. Together our results indicated that normal
      breast epithelial cells can induce apoptosis of breast cancer cells through IGFBP
      3 and maspin. These findings provide a molecular hypothesis for the long observed
      inhibitory effect of normal surrounding cells on breast cancer development.

PMID- 17446557
TI  - Consequences of membrane protein overexpression in Escherichia coli.
AB  - Overexpression of membrane proteins is often essential for structural and
      functional studies, but yields are frequently too low. An understanding of the
      physiological response to overexpression is needed to improve such yields.
      Therefore, we analyzed the consequences of overexpression of three different
      membrane proteins (YidC, YedZ, and LepI) fused to green fluorescent protein (GFP)
      in the bacterium Escherichia coli and compared this with overexpression of a
      soluble protein, GST-GFP. Proteomes of total lysates, purified aggregates, and
      cytoplasmic membranes were analyzed by one- and two-dimensional gel
      electrophoresis and mass spectrometry complemented with flow cytometry,
      microscopy, Western blotting, and pulse labeling experiments. Composition and
      accumulation levels of protein complexes in the cytoplasmic membrane were
      analyzed with improved two-dimensional blue native PAGE. Overexpression of the
      three membrane proteins, but not soluble GST-GFP, resulted in accumulation of
      cytoplasmic aggregates containing the overexpressed proteins, chaperones (DnaK/J
      and GroEL/S), and soluble proteases (HslUV and ClpXP) as well as many precursors
      of periplasmic and outer membrane proteins. This was consistent with lowered
      accumulation levels of secreted proteins in the three membrane protein
      overexpressors and is likely to be a direct consequence of saturation of the
      cytoplasmic membrane protein translocation machinery. Importantly accumulation
      levels of respiratory chain complexes in the cytoplasmic membrane were strongly
      reduced. Induction of the acetate-phosphotransacetylase pathway for ATP
      production and a down-regulated tricarboxylic acid cycle indicated the activation
      of the Arc two-component system, which mediates adaptive responses to changing
      respiratory states. This study provides a basis for designing rational strategies
      to improve yields of membrane protein overexpression in E. coli.

PMID- 17446558
TI  - Three-dimensional perfusion culture of human adipose tissue-derived endothelial
      and osteoblastic progenitors generates osteogenic constructs with intrinsic
      vascularization capacity.
AB  - In this study, we aimed at generating osteogenic and vasculogenic constructs
      starting from the stromal vascular fraction (SVF) of human adipose tissue as a
      single cell source. SVF cells from human lipoaspirates were seeded and cultured
      for 5 days in porous hydroxyapatite scaffolds by alternate perfusion through the
      scaffold pores, eliminating standard monolayer (two-dimensional [2D]) culture.
      The resulting cell-scaffold constructs were either enzymatically treated to
      extract and characterize the cells or subcutaneously implanted in nude mice for 8
      weeks to assess the capacity to form bone tissue and blood vessels. SVF cells
      were also expanded in 2D culture for 5 days and statically loaded in the
      scaffolds. The SVF yielded 5.9 +/- 3.5 x 10(5) cells per milliliter of
      lipoaspirate containing both mesenchymal progenitors (5.2% +/- 0.9% fibroblastic
      colony forming units) and endothelial-lineage cells (54% +/- 6% CD34+/CD31+
      cells). After 5 days, the total cell number was 1.8-fold higher in 2D than in
      three-dimensional (3D) cultures, but the percentage of mesenchymal- and
      endothelial-lineage cells was similar (i.e., 65%-72% of CD90+ cells and 7%-9% of
      CD34+/CD31+ cells). After implantation, constructs from both conditions contained
      blood vessels stained for human CD31 and CD34, functionally connected to the host
      vasculature. Importantly, constructs generated under 3D perfusion, and not those
      based on 2D-expanded cells, reproducibly formed bone tissue. In conclusion,
      direct perfusion of human adipose-derived cells through ceramic scaffolds
      establishes a 3D culture system for osteoprogenitor and endothelial cells and
      generates osteogenic-vasculogenic constructs. It remains to be tested whether the
      presence of endothelial cells accelerates construct vascularization and could
      thereby enhance implanted cell survival in larger size implants. Disclosure of
      potential conflicts of interest is found at the end of this article.

PMID- 17446559
TI  - Promoting effects of serotonin on hematopoiesis: ex vivo expansion of cord blood
      CD34+ stem/progenitor cells, proliferation of bone marrow stromal cells, and
      antiapoptosis.
AB  - Serotonin is a monoamine neurotransmitter that has multiple extraneuronal
      functions. We previously reported that serotonin exerted mitogenic stimulation on
      megakaryocytopoiesis mediated by 5-hydroxytryptamine (5-HT)2 receptors. In this
      study, we investigated effects of serotonin on ex vivo expansion of human cord
      blood CD34+ cells, bone marrow (BM) stromal cell colony-forming unit-fibroblast
      (CFU-F) formation, and antiapoptosis of megakaryoblastic M-07e cells. Our results
      showed that serotonin at 200 nM significantly enhanced the expansion of CD34+
      cells to early stem/progenitors (CD34+ cells, colony-forming unit-mixed [CFU
      GEMM]) and multilineage committed progenitors (burst-forming unit/colony-forming
      unit-erythroid [BFU/CFU-E], colony-forming unit-granulocyte macrophage, colony
      forming unit-megakaryocyte, CD61+ CD41+ cells). Serotonin also increased nonobese
      diabetic/severe combined immunodeficient repopulating cells in the expansion
      culture in terms of human CD45+, CD33+, CD14+ cells, BFU/CFU-E, and CFU-GEMM
      engraftment in BM of animals 6 weeks post-transplantation. Serotonin alone or in
      addition to fibroblast growth factor, platelet-derived growth factor, or vascular
      endothelial growth factor stimulated BM CFU-F formation. In M-07e cells,
      serotonin exerted antiapoptotic effects (annexin V, caspase-3, and propidium
      iodide staining) and reduced mitochondria membrane potential damage. The addition
      of ketanserin, a competitive antagonist of 5-HT2 receptor, nullified the
      antiapoptotic effects of serotonin. Our data suggest the involvement of serotonin
      in promoting hematopoietic stem cells and the BM microenvironment. Serotonin
      could be developed for clinical ex vivo expansion of hematopoietic stem cells for
      transplantation. Disclosure of potential conflicts of interest is found at the
      end of this article.

PMID- 17446560
TI  - Thoracic aortas from multiorgan donors are suitable for obtaining resident
      angiogenic mesenchymal stromal cells.
AB  - The clinical use of endothelial progenitor cells is hampered by difficulties in
      obtaining an adequate number of functional progenitors. This study aimed to
      establish whether human thoracic aortas harvested from healthy multiorgan donors
      can be a valuable source of angiogenic progenitors. Immunohistochemical tissue
      studies showed that two distinct cell populations with putative stem cell
      capabilities, one composed of CD34+ cells and the other of c-kit+ cells, are
      present in between the media and adventitia of human thoracic aortas. Ki-67+
      cells with high growth potential were located in an area corresponding to the
      site of CD34+ and c-kit+ cell residence. We thus isolated cells (0.5
      approximately 2.0 x 10(4) aortic progenitors per 25 cm2) which, upon culturing,
      coexpressed molecules of mesenchymal stromal cells (i.e., CD44+, CD90+, CD105+)
      and showed a transcript expression of stem cell markers (e.g., OCT4, c-kit, BCRP
      1, Interleukin-6) and BMI-1. Cell expansion was adequate for use in a clinical
      setting. A subset of cultured cells acquired the phenotype of endothelial cells
      in the presence of vascular endothelial growth factor (e.g., increased expression
      of KDR and von Willebrand factor positivity), as documented by flow cytometry,
      immunofluorescence, electron microscopy, and reverse transcription-polymerase
      chain reaction assays. An in vitro angiogenesis test kit revealed that cells were
      able to form capillary-like structures within 6 hours of seeding. This study
      demonstrates that thoracic aortas from multiorgan donors yield mesenchymal
      stromal cells with the ability to differentiate in vitro into endothelial cells.
      These cells can be used for the creation of an allogenic bank of angiogenic
      progenitors, thus providing new options for restoring vascularization at ischemic
      sites. Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 17446561
TI  - Expression of Tie-2 and other receptors for endothelial growth factors in acute
      myeloid leukemias is associated with monocytic features of leukemic blasts.
AB  - We investigated the expression of Tie-2 in primary blasts from 111 patients with
      acute myeloid leukemia (AML) to evaluate a possible linkage between the
      expression of this receptor and the immunophenotypic and biologic properties of
      leukemic blasts. Tie-2 was expressed at moderate and high levels in 39 and 23 of
      111 AMLs, respectively. The analysis of the immunophenotype clearly showed that
      Tie-2 expression in AML was associated with monocytic features. Interestingly,
      Tie-2 expression on AML blasts was associated with concomitant expression of
      other receptors for endothelial growth factors, such as vascular endothelial
      growth factor receptor 1 (VEGF-R1), -R2, and -R3. Tie-2(+) AMLs were
      characterized by high blast cell counts at diagnosis, a high frequency of Flt3
      mutations, and increased Flt3 expression. The survival of Tie-2(+) AMLs is
      sustained through an autocrine pattern involving Angiopoietin-1 and Tie-2, as
      suggested by experiments showing induction of apoptosis in Tie-2(+) AMLs by
      agents preventing the binding of angiopoietins to Tie-2. Finally, the in vitro
      growth of Tie-2(+) AMLs in endothelial culture medium supplemented with VEGF and
      angiopoietins resulted in their partial endothelial differentiation. These
      observations suggest that Tie-2(+) AMLs pertain to a mixed monocytic/endothelial
      lineage, derived from the malignant transformation of the normal counterpart
      represented by monocytic cells expressing endothelial markers. The autocrine
      angiopoietin/Tie-2 axis may represent a promising therapeutic target to improve
      the outcome of patients with monocytic AML. Disclosure of potential conflicts of
      interest is found at the end of this article.

PMID- 17446562
TI  - Dissecting the molecular hierarchy for mesendoderm differentiation through a
      combination of embryonic stem cell culture and RNA interference.
AB  - Although there is a criticism that embryonic stem (ES) cell differentiation does
      not always reflect the differentiation process involved in mouse development, it
      is a suitable model system to dissect the specific differentiation pathway. We
      established the culture conditions that selectively differentiated mouse ES cells
      into three germ layers containing mesendoderm, definitive endoderm (DE), visceral
      endoderm (VE), mesoderm, and neuroectoderm. However, the molecular mechanisms of
      differentiation under each specific condition still remain unclear. Here, in
      combination with the RNA interference-mediated gene knockdown (KD) method, we
      show that Eomesodermin (Eomes), Mixl1, Brachyury (T), and GATA6 are major
      molecular determinants in the differentiation of mesendoderm, DE, VE, and
      mesoderm. Eomes plays a pivotal role in an early stage of mesendoderm
      differentiation, whereas Mixl1 does the same in the later stage where mesendoderm
      differentiates into DE. Further analyses of quantitative reverse transcription
      polymerase chain reaction and overexpression of Mixl1 demonstrated that Mixl1 is
      genetically a downstream molecule of Eomes. In addition, both Eomes and Mixl1 act
      as negative regulators of T expression. This strategy also reveals that Eomes and
      T play cell-autonomous roles in platelet-derived growth factor receptor alpha
      (PDGFRalpha)+ vascular endothelial growth factor receptor 2 (VEGFR2)+ and
      PDGFRalpha+ mesoderm generations, respectively. Our results obtained from this
      study are fully consistent with previous knockout studies of those genes. The
      present study, therefore, demonstrates that the major molecular mechanism
      underlying in vitro ES cell differentiation largely recapitulates that in actual
      embryogenesis, and the combination of our culture system and RNAi-mediated gene
      KD is an useful tool to elucidate the molecular hierarchy in in vitro ES cell
      differentiation. Disclosure of potential conflicts of interest is found at the
      end of this article.

PMID- 17446563
TI  - ATP modulates cell proliferation and elicits two different electrophysiological
      responses in human mesenchymal stem cells.
AB  - Bone marrow-derived human mesenchymal stem cells (hMSCs) have the potential to
      differentiate into several cell lines. Extracellular adenosine 5'-triphosphate
      (ATP) acts as a potent signaling molecule mediating cell-to-cell communication.
      Particular interest has been focused in recent years on the role of ATP in stem
      cell proliferation and differentiation. In the present work, we demonstrate that
      hMSCs at early stages of culture (P0-P5) spontaneously release ATP, which
      decreases cell proliferation. Increased hMSC proliferation is induced by the
      unselective P2 antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonate
      (PPADS) and by the selective P2Y1 antagonist 2'-deoxy-N6-methyladenosine3',5'
      bisphosphate (MRS 2179). A functional role of extracellular ATP in modulating
      ionic conductances with the whole-cell and/or perforated patch-clamp techniques
      was also investigated. Exogenous ATP increased both the voltage-sensitive outward
      and inward currents in 47% of cells, whereas, in 31% of cells, only an increase
      in inward currents was found. Cells responding in this dual manner to ATP
      presented different resting membrane potentials. Both ATP-induced effects had
      varying sensitivity to the P2 antagonists PPADS and MRS 2179. Outward ATP
      sensitive currents are carried by potassium ions, since they are blocked by
      cesium replacement and are Ca2+ -dependent because they are eliminated in the
      presence of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. On the
      basis of different electrophysiological and pharmacological characteristics, we
      conclude that outward ATP-sensitive currents are due to Ca2+ -dependent K+ 
      channel activation following stimulation of P2Y receptors, whereas inward ATP
      sensitive currents are mediated by P2X receptor activation. In summary, ATP
      released in early life stages of hMSCs modulates their proliferation rate and
      likely acts as one of the early factors determining their cell fate. Disclosure
      of potential conflicts of interest is found at the end of this article.

PMID- 17446564
TI  - Prevention of graft-versus-host disease by intra-bone marrow injection of donor T
      cells.
AB  - We have recently found that intra-bone marrow-bone marrow transplantation (IBM
      BMT) can be used to prevent graft-versus-host disease (GvHD), even when intensive
      donor lymphocyte infusion (DLI) is carried out. In the present study, in
      conjunction with IBM-BMT, allogeneic splenic T cells as DLI were also injected
      into the bone marrow cavity of lethally irradiated (8.5 Gy) recipients. The
      extent of GvHD was compared with that of recipients that had received allogeneic
      IBM-BMT plus i.v. injection of allogeneic T cells (intravenous DLI [IV-DLI]).
      GvHD in recipients treated with allogeneic IBM-BMT plus IBM-DLI was far milder
      than in those treated with allogeneic IBM-BMT plus IV-DLI. This was confirmed
      macroscopically and histopathologically. The frequency of regulatory T cells
      (Tregs) detected as CD4(+)CD25(+) and CD4(+)Foxp3(+) cells was significantly
      higher in recipients treated with IBM-BMT plus IBM-DLI than in those treated with
      IBM-BMT plus IV-DLI. Donor-derived helper T (Th) cells polarized to Th2 type in
      recipients treated with IBM-BMT plus IBM-DLI, whereas Th1 cells were dominant in
      recipients treated with IBM-BMT plus IV-DLI. Furthermore, the production of
      transforming growth factor-beta and hepatocyte growth factor from bone marrow
      stromal cells was enhanced after IBM-DLI. Thus, IBM-BMT plus IBM-DLI seem to
      preferentially induce Tregs and Th2, resulting in the prevention of GvHD.
      Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 17446565
TI  - Exploring the spatial dynamics of alcohol outlets and Child Protective Services
      referrals, substantiations, and foster care entries.
AB  - Controlling for neighborhood demographic characteristics, this study examined the
      relationship of alcohol outlets with rates of Child Protective Services (CPS)
      referrals, substantiations, and foster care entries from 1998-2003 in 579 zip
      codes in California. Data for this panel study were analyzed using spatial random
      effects panel models. Zip codes with higher concentrations of off-premise alcohol
      outlets (e.g., convenience or liquor stores) and proportions of Black residents
      had higher rates of maltreatment. Higher average household size and median
      household income were generally related to lower child maltreatment rates. More
      specifically, the model derived estimates that an average decrease of one off
      premise outlet per zip code would reduce total referrals to CPS in the 579 zip
      codes by 1,040 cases, substantiations by 180 cases, and foster care entries by 93
      cases. Characteristics of adjacent zip codes also were related to maltreatment
      rates in local neighborhoods, indicating a spatial dynamic to this relationship.
      Reductions in number of alcohol outlets per zip code, particularly off-premise
      outlets, may result in lower rates of child maltreatment.

PMID- 17446566
TI  - The impact of parental alcohol or drug removals on foster care placement
      experiences: a matched comparison group study.
AB  - Research has established the coincidence of parental alcohol and other drug (AOD)
      use and child maltreatment, but few studies have examined the placement
      experiences and outcomes of children removed because of parental AOD use. The
      present study examines demographic characteristics and placement experiences of
      children removed from their homes because of parental AOD use (n = 1,333), first
      in comparison to the remaining sample of children in foster care (n = 4,554),
      then in comparison to a matched comparison group of children in foster care who
      were removed for other reasons (n = 1,333). Relative to the comparison sample,
      children removed for parental AOD use are less likely to experience co-occurring
      removal because of neglect and physical or sexual abuse and are more likely to be
      placed in relative foster care. In addition, these children remain in care
      longer, experience similar rates of reunification, and have significantly higher
      rates of adoption.

PMID- 17446567
TI  - Parental substance use disorders and child maltreatment: overlap, gaps, and
      opportunities.
AB  - There are relatively few empirically sound studies or nationally representative
      data on the number of children in Child Welfare Services (CWS) who are affected
      by their parents' substance abuse or dependence. The two systems that could
      systematically monitor this population, CWS and substance abuse treatment, are
      not required to capture the data elements that would identify families in both
      systems. The studies that are based on CWS populations or parents in treatment
      indicate that there is a substantial overlap in client populations. This review
      provides a summary of the available data; provides estimates of the overlap
      between populations, including the number of infants born each year with prenatal
      substance exposure; and suggests important opportunities to close the data gap
      between the systems. The findings underscore both the need for obtaining accurate
      data within the systems and the opportunities for states to improve their cross
      system data efforts as part of their outcome monitoring.

PMID- 17446568
TI  - Child maltreatment and foster care: unpacking the effects of prenatal and
      postnatal parental substance use.
AB  - Parental substance use is a well-documented risk for children. However, little is
      known about specific effects of prenatal and postnatal substance use on child
      maltreatment and foster care placement transitions. In this study, the authors
      unpacked unique effects of (a) prenatal and postnatal parental alcohol and drug
      use and (b) maternal and paternal substance use as predictors of child
      maltreatment and foster care placement transitions in a sample of 117 maltreated
      foster care children. Models were tested with structural equation path modeling.
      Results indicated that prenatal maternal alcohol use predicted child maltreatment
      and that combined prenatal maternal alcohol and drug use predicted foster care
      placement transitions. Prenatal maternal alcohol and drug use also predicted
      postnatal paternal alcohol and drug use, which in turn predicted foster care
      placement transitions. Findings highlight the potential integrative role that
      maternal and paternal substance use has on the risk for child maltreatment and
      foster care placement transitions.

PMID- 17446569
TI  - The Sacramento Dependency Drug Court: development and outcomes.
AB  - Dependency Drug Courts (DDCs) are a growing method of addressing the functional
      status and reunification success of families involved in child welfare and
      affected by substance use disorders. Despite widespread interest in DDCs, few
      evaluations have appeared in the literature to help inform the discussion about
      their effectiveness. This article provides a description of various types of DDCs
      and reports 24-month reunification rates from the Sacramento DDC. Results
      indicated that DDC participants had higher rates of treatment participation than
      did comparison participants. In addition, at 24 months, 42% of the DDC children
      had reunified versus 27.2% of the comparison children. There were no differences
      in treatment completion or child reunification rates by parent's primary drug
      problem. Rates of recidivism were extremely low for both the DDC and comparison
      groups and did not differ significantly. The results of the present study are
      encouraging and suggest that rigorous, controlled studies are merited to further
      evaluate the effectiveness of DDCs.

PMID- 17446570
TI  - Unique and combined contributions of multiple child abuse types and abuse
      severity to adult trauma symptomatology.
AB  - Studies have documented the co-occurrence and cumulative impact of multiple types
      of child maltreatment on later psychosocial difficulties. Other research suggests
      that child abuse characteristics indicative of severity may also increase risk of
      later adjustment problems. However, little effort has been made to examine the co
      occurrence of both multiple types of maltreatment and abuse severity within a
      single study. The present investigation examines self-reported child maltreatment
      and adult functioning in a geographically diverse sample of 1,396 undergraduate
      students. Results indicate that experiencing multiple types of maltreatment is
      positively associated with more severe abuse. Although increased maltreatment
      types and more severe abuse are each associated with greater trauma
      symptomatology, abuse severity is the stronger of the two predictors. Finally,
      number of maltreatment types and severity of maltreatment interact to predict
      greater levels of trauma symptomatology. These results highlight the importance
      of considering both co-occurring abuse types and severity in research and
      clinical work with adult victims.

PMID- 17446571
TI  - The impact of mock jury gender composition on deliberations and conviction rates
      in a child sexual assault trial.
AB  - This study investigated how the gender composition of mock juries affects
      deliberations and conviction rates in a child sexual assault (CSA) trial. As
      opposed to studies in which mock jurors make decisions as individuals, mock jury
      research allows for investigation of how individual decisions translate into
      group verdicts. Gender composition within mock juries was varied to examine
      whether well-established gender differences in individual judgments affect the
      jury-level decision-making process. Three hundred men and women, in 6-member mock
      juries, heard a fictional CSA trial. During deliberations, proprosecution/
      prodefense statements by women were approximately equal, whereas men made more
      prodefense statements. Women switched votes during deliberations more than did
      men; jurors in woman majority mock juries changed from not guilty to guilty more
      often than did jurors in nonwoman majority juries, and vice versa; and woman
      majority mock juries convicted most often. Findings indicate that predeliberation
      gender differences led to unique jury deliberation strategies and voting
      patterns.

PMID- 17446572
TI  - Can nonoffending mothers of sexually abused children be both ambivalent and
      supportive?
AB  - Some nonoffending parents experience ambivalence in feelings, belief, and
      behavior toward their children after their children's disclosure of sexual abuse.
      Traditionally, it has been assumed that ambivalent nonoffending parents are not
      adequately supportive of their children after disclosure. In contrast, this study
      of 29 nonoffending mothers whose resident partners sexually abused their children
      tests a theoretical model of postdisclosure responses of nonoffending parents in
      which it is hypothesized that parental support and ambivalence can coexist. In a
      partial least squares analysis of this model, no relationship between
      postdisclosure support and ambivalence is found after controlling for variables
      related to ambivalence. These findings lend preliminary support to the
      hypothetical theoretical model, supporting a need for continuing research on the
      constructs of ambivalence and parental support.

PMID- 17446574
TI  - Improving outcomes in pregnancy.

PMID- 17446575
TI  - NHS walk-in centres.

PMID- 17446576
TI  - Palliative care in the community.

PMID- 17446577
TI  - Pathological gambling in Parkinson's disease.

PMID- 17446578
TI  - Regulation of opioid prescribing.

PMID- 17446579
TI  - Case presented does not wash.

PMID- 17446580
TI  - Case for angioplasty to treat angina.

PMID- 17446581
TI  - Time for action on chlamydia.

PMID- 17446582
TI  - Gender neutrality is crucial.

PMID- 17446583
TI  - What about stigma, evidence base, and consistency?

PMID- 17446584
TI  - Data on alcohol hand rubs are equivocal.

PMID- 17446585
TI  - Construction and assumptions of models should be explicit.

PMID- 17446588
TI  - Aspirin reduced risk of cancer in large US study.

PMID- 17446589
TI  - New approach to surgical care aims to improve recovery and reduce length of
      hospital stay.

PMID- 17446590
TI  - Zimbabwean doctors' group calls on world's health professionals to support right
      to treatment.

PMID- 17446591
TI  - Three Russian doctors face trial for vaccine tests.

PMID- 17446592
TI  - Woman loses final round of battle to use her frozen embryos.

PMID- 17446595
TI  - People with diabetes are not given enough information on self care, survey shows.

PMID- 17446596
TI  - Drug company campaign adds to pressure on Dutch doctors to vaccinate against HPV.

PMID- 17446597
TI  - US should ease its travel restrictions on HIV positive people, think tank says.

PMID- 17446598
TI  - Future of historic paintings is uncertain after closure of hospital site.

PMID- 17446599
TI  - Georgian drug misusers switch to Western heroin substitute.

PMID- 17446601
TI  - England's new research funding system leaves some fields of psychiatry out in
      cold.

PMID- 17446610
TI  - MTAS--where are we now?

PMID- 17446611
TI  - Should you tell patients about beneficial treatments that they cannot have? Yes.

PMID- 17446612
TI  - Should you tell patients about beneficial treatments that they cannot have? No.

PMID- 17446613
TI  - Gambling with the nation's health.

PMID- 17446614
TI  - A better way to die.

PMID- 17446615
TI  - When professional opinion is not enough.

PMID- 17446616
TI  - Delirium in older people.

PMID- 17446617
TI  - Asthma.

PMID- 17446618
TI  - Information technology cannot guarantee patient safety.

PMID- 17446624
TI  - Identification and quantification of dolichol and dolichoic acid in neuromelanin
      from substantia nigra of the human brain.
AB  - Neuromelanin (NM) isolated from the substantia nigra of the human brain is found
      to contain a series of dolichoic acids (dol-CA) containing 14-20 isoprene units.
      This is the first observation of dol-CA in a natural system. Using internally
      spiked nor-dolichol and nor-dolichoic acid standards, the concentrations of
      dolichol (dol) and dol-CA present in NM were determined. Remarkably, dol was only
      four times as abundant as dol-CA in NM. The distribution of dol-CA chains lengths
      in NM also differed from that of dol, suggesting that the enzyme(s) responsible
      for the conversion of dol to dol-CA prefer a dolichol substrate containing 19
      isoprene units.

PMID- 17446625
TI  - Introducing DVM: DiVersity Matters (an Association of American Veterinary Medical
      Colleges Initiative).
AB  - Now more than ever, colleges of veterinary medicine (CVMs) are challenged to
      improve the educational experience, build environments that support long-term
      student and faculty success, and create a diverse and competitive workforce.
      Additionally, the nation's fast-evolving racial and ethnic demographics demand
      that the veterinary medical profession be responsive to the emerging needs of
      this changing population. In March 2005, during the 15th Iverson Bell Symposium,
      the Association of American Veterinary Medical Colleges (AAVMC) unveiled its
      DiVersity Matters (DVM) initiative, designed to bring the CVMs closer to
      achieving these goals. Several key objectives of the initiative and their
      possible long-term significance to success of the DiVersity Matters initiative
      are explored here, and CVMs are encouraged to expand efforts to increase racial
      and ethnic diversity in academic veterinary medicine.

PMID- 17446626
TI  - The attitudes of minority junior high and high school students toward veterinary
      medicine.
AB  - There is a documented lack of racial diversity in veterinary medicine. It has
      been suggested that lack of animal ownership by minorities, cultural and ethnic
      biases relating to animals, and a lack of role models of color within the
      veterinary profession are reasons for the lack of racial diversity in veterinary
      medicine. The purpose of this study was to survey the attitudes of minority
      junior high and high school students toward veterinary medicine. It was
      hypothesized that African American and Latino students in New York City (NYC)
      would have limited experience with veterinary medicine and would not have a
      favorable attitude toward the profession. In fact, the survey, which was sent to
      several NYC schools, found that minority students have a positive view of animals
      and of veterinary medicine. The survey also showed that a deficiency of minority
      role models for students, a lack of interest in and enjoyment of veterinary
      medicine on the part of students, a perception on the part of students that
      veterinary medicine does not provide a satisfying lifestyle, and inadequate
      student exposure to the profession are key factors in the lack of racial
      diversity in veterinary medicine.

PMID- 17446627
TI  - Your path to success: advice to people considering a career in health sciences.

PMID- 17446628
TI  - Pathways: Missouri model for enhancing diversity.
AB  - This article describes the structure and principles of the Pathways to Success
      program, created by College of Veterinary Medicine, University of Missouri,
      Columbia, which is making excellent progress in recruiting minority student to
      the College of Veterinary Medicine.

PMID- 17446629
TI  - Native American tribal cultures: implications for veterinary medical education.
AB  - This article reviews the literature from veterinary medicine, tribal education,
      career development, and psychology to focus on the reasons that Native people are
      currently under-represented in the field of veterinary medicine. Educational
      implications and recruitment strategies are suggested. Local, state, and national
      resources are provided to help veterinary medical educators make their programs
      more culturally competent for Native veterinary students and faculty.

PMID- 17446630
TI  - Racial, cultural, and ethnic diversity within US veterinary colleges.
AB  - A comprehensive survey containing 30 questions regarding racial, cultural, and
      ethnic issues was sent electronically to each of the member colleges within the
      Association of American Veterinary Colleges (AAVMC) during 2005. Responses were
      received from 25 of the 28 veterinary colleges in the United States and two
      foreign colleges. Most colleges had more than one respondent complete the survey.
      Since the respondents were not identified and were not uniform in regards to
      position within each college, some responses might have reflected the individual
      respondent's views rather than the college's actual situation or philosophy. The
      information gained from this survey demonstrates strong trends in attitudes to
      and practices with respect to diversity in US veterinary colleges. Three major
      areas were addressed in the survey-college and university environment and
      cultures, faculty and curriculum, and recruitment and retention of veterinary
      students from underrepresented minorities. In many instances, the survey
      confirmed a lack of knowledge about diversity issues at the respondents'
      institutions. These survey results will serve as a benchmark for gauging changes
      in the profession's racial, cultural, and ethnic demographics in the future and
      as a foundation upon which to build effective diversity programs.

PMID- 17446631
TI  - Implementing change in health professions education: stakeholder analysis and
      coalition building.
AB  - The challenges facing the health sciences education fields are more evident than
      ever. Professional health sciences educators have more demands on their time,
      more knowledge to manage, and ever-dwindling sources of financial support. Change
      is often necessary to either keep programs viable or meet the changing needs of
      health education. This article outlines a simple but powerful three-step tool to
      help educators become successful agents of change. Through the application of
      principles well known and widely used in business management, readers will
      understand the concepts behind stakeholder analysis and coalition building. These
      concepts are part of a powerful tool kit that educators need in order to become
      effective agents of change in the health sciences environment. Using the example
      of curriculum change at a school of veterinary medicine, we will outline the
      three steps involved, from stakeholder identification and analysis to building
      and managing coalitions for change.

PMID- 17446632
TI  - Change in higher education: understanding and responding to individual and
      organizational resistance.
AB  - In many fields, the ability of educators and practitioners to cope with rapid
      change is essential to sustained success. In veterinary medical education, as in
      other scientific disciplines, meaningful change is challenging to achieve and
      subject to resistance from many individual and organizational norms. Individual
      concerns often relate to fears of instability or uncertainty, loss of current
      status, or effects on individual time and workload. Sources of organizational
      resistance may include a conservative culture, fierce protection of current
      practices, and prevalence of disciplinary or territorial viewpoints. In academia,
      especially in scientific or medical fields, individuals appear to be strongly
      independent and conservative in nature, and generally skeptical of educational
      change. In this environment, a highly participatory process, with regular
      communication strategies and demonstrations or evidence that supports proposed
      changes, can be useful in facilitating change. An understanding of the nature of
      complex change, as well as of the reasons underlying resistance to change, and
      some methods to overcome these barriers are highly valuable tools for educational
      leaders.

PMID- 17446633
TI  - "If it's tuesday, I must be the student": lessons learned from the other side of
      the classroom.
AB  - After teaching veterinary students for over 10 years, the author returned to
      graduate school as a part-time doctoral student in educational administration and
      policy studies. Sitting in the student's chair brought back an acute awareness of
      the submissive position of the student, the daunting prospects of navigating a
      university system, and the challenges of managing the workload of a degree
      program. The experience also provided a fresh perspective on instruction,
      including course delivery, effective use of class time, and the potential impact
      of the language one uses with students. These insights on teaching and learning
      and on the student's viewpoint may help educators become more empathetic and
      effective instructors and mentors of veterinary students.

PMID- 17446634
TI  - Admissions test for the degree course in veterinary medicine in Italy, 2005.
AB  - In Italy, access to the degree course in veterinary medicine is regulated each
      academic year by a government decree that sets the maximum student intake number
      for each of the 14 existing faculties. Candidates are selected by means of a
      multiple-choice test on the following subjects: logic and general knowledge,
      biology, chemistry, physics, and mathematics. Data for the 2005/2006 academic
      year are presented here. Overall, 4,495 candidates took the test and 1,415
      (31.5%) qualified. The questions relating to physics and mathematics were more
      difficult than those in other subjects (p < 0.001). Logic and general knowledge
      was the subject in which candidates' knowledge was best. Separate data for each
      of the 14 Italian faculties are presented, along with the cut-off score for
      admission. In addition, a "difficulty admission index" has been calculated for
      each faculty centre.

PMID- 17446635
TI  - Evaluation of the level of difficulty of patient cases for veterinary problem
      solving examination: a preliminary comparison of three taxonomies of learning.
AB  - An important issue that has received insufficient attention in the use of problem
      based learning in the medical curriculum is the mode of assessing the level of
      difficulty of patient cases. In the present study, the level of difficulty of
      case-based questions in a veterinary degree final examination in reproduction was
      evaluated. First, cognitive taxonomies were evaluated to clarify whether
      qualitative methods such as Bloom's taxonomy, the Structure of the Observed
      Learning Outcome (SOLO) taxonomy, and the Amsterdam Clinical Challenge Scale
      (ACCS) differed from each other as evaluation tools for problem-based cases.
      Using these taxonomies, 30 case-based questions from the final examination in
      reproduction in the Helsinki veterinary program were initially evaluated to
      determine which one was best suited to the evaluation of the difficulty of cases.
      In follow-up, the same cases were also evaluated by an experienced veterinary
      instructor in reproduction, with the aim of gaining insight into using these
      approaches to evaluating difficulty. It would appear, from this preliminary
      assessment, that the SOLO taxonomy may be the most suitable for evaluating the
      difficulty of patient cases, since the instructor's quality rating resembled more
      closely the SOLO than the Bloom taxonomy or the ACCS. It is to be emphasized that
      the purpose of this study was to provide a preliminary evaluation of possible
      approaches that might be used to assess patient-case difficulty. Resolving all
      issues will require a greater number of evaluations of all components.

PMID- 17446636
TI  - Effects of a veterinary student leadership program on measures of stress and
      academic performance.
AB  - Assuming leadership roles in veterinary student governance or club activities
      could be considered an added stressor for students because of the impact on time
      available for personal and academic activities. The study reported here evaluated
      the effects of participation in a leadership program and leadership activity
      across two classes of veterinary students on measures of stress, using the
      Derogatis Stress Profile (DSP), and on veterinary school academic performance,
      measured as annual grade-point average (GPA) over a three-year period. Program
      participants and their classmates completed the DSP three times across the first
      three years of veterinary school. On average, participating students reported
      self-declared stress levels that were higher and measured DSP stress levels that
      were lower than those of the general population. Students were more likely to
      assume elected or appointed leadership roles while in their first three years of
      the veterinary degree program if they participated in the optional leadership
      program and demonstrated lower stress in several dimensions. Some increased
      stress, as measured in some of the DSP stress dimensions, had a small but
      statistically significant influence on professional school GPA. The study
      determined that the most important predictors of students' cumulative GPA across
      the three-year period were the GPA from the last 45 credits of pre-veterinary
      coursework and their quantitative GRE scores. The results of the study indicate
      that neither participation in the leadership program nor taking on leadership
      roles within veterinary school appeared to influence veterinary school academic
      performance or to increase stress.

PMID- 17446637
TI  - Involving practitioners in continuing education needs assessment: use of the
      nominal group technique.
AB  - The nominal group technique (NGT) is described. An example of this method is
      provided. The goal was to identify clinical cases that could be used in a
      practitioner self-assessment tool. Practitioners in three groups were asked to
      keep a journal about cases they saw in the two weeks prior to their group
      discussion, individually provide case ideas within the group, and prioritize the
      cases individually. The groups provided over 192 case descriptions that can be
      used in a self-assessment tool for small animal practitioners. The NGT is a
      valuable tool that can identify and prioritize issues.

PMID- 17446638
TI  - Veterinary students' views on animal patients and human clients, using Q
      methodology.
AB  - Veterinarians serve two masters: animal patients and human clients. Both animal
      patients and human clients have legitimate interests, and conflicting moral
      claims may flow from these interests. Earlier research concludes that veterinary
      students are very much aware of the complex and often paradoxical relationship
      they have and will have with animals. In this article the views of veterinary
      students about their anticipated relationship with animal patients and human
      clients are studied. The main part of the article describes discourses of first
      year and fourth-year students about their (future) relationship with animals and
      their caretakers, for which Q-methodology is used. At the end of the article, the
      discourses are related to the students' gender and their workplace preferences.

PMID- 17446639
TI  - Acquainting veterinary students with careers in the pharmaceutical industry.
AB  - Careers in the pharmaceutical industry were revealed in modules facilitated by
      senior scientists from companies that sponsor the Cornell Leadership Program for
      Veterinary Students. One module was structured as a series of interviews for
      different positions in industry, the other as a competition between hypothetical
      companies created by students. The interview-based module stimulated wide-ranging
      discussion of the activities and responsibilities of veterinarians employed in a
      discovery-intensive pharmaceutical firm and of the characteristics such companies
      seek in prospective employees, from both professional and personal perspectives.
      The second module explored the drug discovery and development process from the
      perspective of animal-health companies that are competitors in the market for
      animal health care products. The exercise provided insights into the manner in
      which companies discover new chemical entities, screen candidate drugs, allocate
      resources, and pursue the development of products through testing, licensing, and
      distribution.

PMID- 17446640
TI  - The use of multi-detector row computed tomography (MDCT) as an alternative to
      specimen preparation for anatomical instruction.
AB  - The purpose of the study reported here was to establish a method of teaching
      veterinary anatomy, including radiologic anatomy, for clinical practice using
      computer-aided diagnosis (CAD). Two clinically healthy dogs and three cats were
      scanned using multi-detector row computed tomography (MDCT). Images were made by
      means of imaging processing software. At the workstation, by observing the
      transverse, dorsal-plane, or sagittal sections and three-dimensional (3D) images
      simultaneously, it is much easier to understand the 3D anatomical structure. With
      this educational support system, anatomical figures can be explained using living
      animals instead of specimens. In addition, clinical representative examples can
      be used to show anatomical disorders to students. Veterinary students (N = 62)
      who filled out a questionnaire evaluating how the method aided their
      understanding of both experimental study and clinical examples gave it a score of
      88.2 +/- 20.6 (Mean +/- SD) on a visual analog scale. This system can enhance
      veterinary students' understanding and interest in anatomy and can enable us to
      offer them a quality veterinary medical education. We concluded that CAD is a
      useful new option not only for clinical service but also for veterinary
      education.

PMID- 17446641
TI  - Why dissection videos should not replace cadaver prosections in the gross
      veterinary anatomy curriculum: results from a comparative study.
AB  - The goal of our study was to evaluate the impact of a tool intended to eliminate
      large-animal cadavers from the anatomy laboratory, in view of their prohibitive
      cost and the logistic difficulties they pose. We sought to determine whether a
      commented video of the bovine abdominal cavity could effectively replace a
      prosection of this region. The hypothesis was that students receiving video
      instruction would achieve lower scores on a post-instructional exam than those
      benefiting from a commented cadaver prosection. A commented video of the bovine
      abdominal cavity was compared to a prosection covering identical material.
      Seventy-five first-year students, having received no prior instruction on the
      region of interest, were divided into two groups of equivalent knowledge: group A
      received prosection instruction (N = 38) and group B, video instruction (N = 37).
      Following instruction, students completed a test on a cadaver, requiring that
      they correctly match 15 labeled structures with a list of 40 possible answers.
      Statistical analysis consisted of a repeated-measures linear model with group (A
      vs. B) as a between-subject factor and time (pre- vs post-test) as a within
      subject factor, with significance at p < or = 0.05. Students in group A achieved
      mean scores of 9.21 +/- 0.31, while those in group B scored 7.65 +/- 0.31.
      Although both groups significantly improved following instruction, there was a
      statistically significant difference in the post-instruction scores between
      groups A and B (p = 0.0007), in favor of the prosection group. The major comment
      in favor of cadaver prosection pertained to the sensory experience; in favor of
      video instruction, students stressed accessibility to the pedagogical material
      for autonomous learning and revision as well as superior viewing compared to the
      setup adopted for prosections. In conclusion, while our data suggest that cadaver
      prosections are superior to video demonstrations, it is apparent that students
      can learn bovine abdominal anatomy by both methods. Future investigations on the
      subject of alternative teaching methods are warranted.

PMID- 17446642
TI  - Errors in radiographic interpretation made by veterinary students.
AB  - As a means of identifying student weaknesses in radiographic interpretation that
      could be used as foci for teaching, a cohort of 96 students joining the final
      year radiology rotation were randomly allocated to one of three radiographic
      interpretation quizzes, each based on radiographs of small-animal patients
      together with the signalment and a brief, relevant history. Students' quiz scores
      were analyzed by multiple logistic regression, using an outcome variable with the
      score for each item as numerator and maximum possible mark as denominator.
      Students' median quiz score was 49% of the maximum (range 23-80%). Students were
      more likely to gain a mark for items based on abnormal radiographs than for those
      based on normal radiographs (odds ratio 3.4, p < 0.001). Skeletal radiographs
      were associated with lower scores (OR 0.75, p = 0.03). The fewest marks were
      awarded for interpretation of a radiograph of a normal canine stifle and
      interpretation of a radiograph of a normal canine pelvis; these items were
      misinterpreted as abnormal by 86% and 80% of the students, respectively.
      Students' tendency to over-interpret normal radiographs may reflect a lack of
      knowledge of radiographic anatomy or an unrealistically high expectation that the
      radiographs are abnormal.

PMID- 17446643
TI  - Teaching veterinary radiography by e-learning versus structured tutorial: a
      randomized, single-blinded controlled trial.
AB  - Case-based e-learning may allow effective teaching of veterinary radiology in the
      field of equine orthopedics. The objective of this study was to investigate the
      effectiveness of a new case-based e-learning tool, compared with a standard
      structured tutorial, in altering students' knowledge and skills about
      interpretation of radiographs of the digit in the horse. It was also designed to
      assess students' attitudes toward the two educational interventions. A
      randomized, single-blinded, controlled trial of 96 fourth-year undergraduate
      veterinary students, involving an educational intervention of either structured
      tutorial or case-based e-learning, was performed. A multiple-choice examination
      based on six learning outcomes was carried out in each group after the session,
      followed by an evaluation of students' attitudes toward their session on a seven
      point scale. Text blanks were available to students to allow them to comment on
      the educational interventions and on their learning outcomes. Students also
      rated, on a Likert scale from 1 to 7, their performance for each specific
      learning outcome and their general ability to use a systematic approach in
      interpreting radiographs. Data were analyzed using the Mann-Whitney test, the t
      test, and the equivalence test. There was no significant difference in student
      achievement on course tests. The results of the survey suggest positive student
      attitudes toward the e-learning tool and illustrate the difference between
      objective ratings and subjective assessments by students in testing a new
      educational intervention.

PMID- 17446644
TI  - A new system to reduce formaldehyde levels improves safety conditions during
      gross veterinary anatomy learning.
AB  - Dissection is a very useful method of learning veterinary anatomy. However,
      formaldehyde, which is widely used to preserve cadavers, is an irritant, and it
      has recently been classified as a carcinogen. In 1997, the Instituto Nacional de
      Seguridad e Higiene en el Trabajo [National Institute of Workplace Security and
      Hygiene] found that the levels of formaldehyde in our dissection room were above
      the threshold limit values. Unfortunately, no optimal substitute for formaldehyde
      is currently available. Therefore, we designed a new ventilation system that
      combines slow propulsion of fresh air from above the dissection table and rapid
      aspiration of polluted air from the perimeter. Formaldehyde measurements
      performed in 2004, after the introduction of this new system into our dissection
      laboratory, showed a dramatic reduction (about tenfold, or 0.03 ppm). A suitable
      propelling/aspirating air system successfully reduces the concentration of
      formaldehyde in the dissection room, significantly improving safety conditions
      for students, instructors, and technical staff during gross anatomy learning.

PMID- 17446645
TI  - How useful is plastination in learning anatomy?
AB  - In recent years plastination has begun to revolutionize the way in which human
      and veterinary gross anatomy can be presented to students. The study reported
      here assessed the efficacy of plastinated organs as teaching resources in an
      innovative anatomy teaching/learning system. The main objective was to evaluate
      whether the use of plastinated organs improves the quality of teaching and
      learning of anatomy. For this purpose, we used an interdepartmental approach
      involving the departments of Veterinary Anatomy, Human Anatomy, Veterinary
      Surgery, and Education Development and Research Methods. The knowledge base of
      control and experimental student groups was examined before and after use of the
      fixed or plastinated resources, respectively, to gather information evaluating
      the effectiveness of these teaching resources. Significant differences (p <
      0.001) between control and experimental groups of Human and Veterinary Anatomy
      were observed in the post-test results. The Veterinary Surgery students had the
      most positive opinion of the use of plastinated specimens. Using these data, we
      were able to quantitatively characterize the use of plastinated specimens as
      anatomy teaching resources. This analysis showed that all the plastinated
      resources available were heavily used and deemed useful by students. Although the
      properties of plastinated specimens accommodate student needs at various levels,
      traditional material should be used in conjunction with plastinated resources.

PMID- 17446646
TI  - Teaching histology to first-year veterinary science students using virtual
      microscopy and traditional microscopy: a comparison of student responses.
AB  - Virtual microscopy (VM) is a comparatively recent innovation that is
      revolutionizing both the teaching of microscopic structure in human medicine and
      the concept of online diagnosis and telemedicine. The interactivity of the
      various commercially available browsers attempts to simulate the experience of
      looking down a microscope while offering advantages over traditional microscopy
      that include clarity of image, reduced infrastructure, and high flexibility, as
      the images are accessible online. We developed our own VM system, including
      customized software and a browser that was simple and intuitive to use, with the
      added advantage of further modifications possible to assist student learning. In
      this article, we report on a preliminary study wherein VM was introduced to
      veterinary science students in one course and directly compared to traditional
      microscopy to determine whether students would readily accept this new technology
      and which aspects of VM were advantageous. Responses from a survey form showed
      that students rated VM significantly higher than traditional microscopy as a tool
      to learn histology because it offers clearer images, the ability to learn
      collaboratively, more effective use of time, and the flexibility of online
      learning. Students also indicated a strong preference for the use of VM in future
      courses. These results suggest that VM is a flexible and enjoyable resource that
      could be useful to enhance the learning of microscopic structure in veterinary
      science courses.

PMID- 17446647
TI  - The case correlation assignment: connecting antemortem and postmortem data in the
      senior year at Iowa State University.
AB  - Instructors of the senior necropsy rotation at Iowa State University experienced
      difficulty ensuring similarity of case exposure and workload during the year.
      This was problematic during times of low caseload, as, without necropsy cases,
      there was no uniform method for training or assessing students. A new assignment,
      the Case Correlation Assignment (CCA), was created in order to improve the
      educational rigor and consistency of the rotation, increase utilization of
      necropsy cases as teaching material, and provide students more opportunities to
      correlate clinical pathology data with lesions. The CCA provides an opportunity
      for senior students to present and explain the antemortem and postmortem findings
      from an ISU-VTH patient in case report format. This illustrated report is
      submitted via WebCT. Students receive feedback on WebCT through a scoring rubric
      and written comments from the instructor. Since 2002, approximately 420 students
      have completed this assignment. The average score on the assignment over the four
      year period is 94.7%. Despite complaints about the hard work required, students
      generally report that writing the CCA is a valuable learning experience. The CCA
      allows for greater utilization of necropsy cases and the incorporation of
      clinical pathology into necropsy cases. Currently, the CCA is used in a peer
      assessment assignment in the junior pathology course and has been incorporated
      into case-based teaching courses. The CCA has been revised and expanded over the
      past four years in response to student feedback and to the discovery of new ways
      to utilize the completed assignments as teaching material.

PMID- 17446648
TI  - Improving response rates: introducing an anonymous longitudinal survey research
      protocol for veterinary medical students.
AB  - With the Journal of Veterinary Medical Education's recent summer 2005 theme issue
      on stress, the mental-health concerns of veterinary medical students has been
      brought to the forefront of the field. Since it is anticipated that research on
      this topic will continue and that educational institutions may implement changes
      based upon these results, it is of the utmost importance that this research be of
      the highest quality. Of particular concern with human-subject inquiries are
      response rates and confidentiality. In order to accommodate these concerns, an
      example of a survey research protocol that promotes high response rates and
      minimizes threats to internal validity influenced by student mistrust in
      assurances of confidentiality is presented. Specifically, the protocol is
      designed to ensure anonymity and to preserve the ability to track students
      longitudinally through the use of anonymous longitudinal identifiers. This
      protocol was tested with the first-year class of veterinary medical students at
      Kansas State University in October 2004 and March 2005. The two data collection
      periods yielded 90% and 76% response rates, respectively. The matching rate of
      participants, according to the anonymous longitudinal identifiers from Time 1 to
      Time 2, was 88%.

PMID- 17446649
TI  - Assessment of incidental learning of medical terminology in a veterinary
      curriculum.
AB  - The objective of this study was to determine whether students in a veterinary
      curriculum at Mississippi State University would gain an understanding of medical
      terminology, as they matriculate through their courses, comparable to that
      obtained during a focused medical terminology unit of study. Evaluation of
      students' incidental learning related to medical terminology during the 2004/2005
      and 2005/2006 academic years indicated that 88.7% and 81.9% of students,
      respectively, scored above 70% on a medical terminology exam by the end of the
      first year of the curriculum. For the 2004/2005 academic, 67.6% increased their
      percentage of correct answers above 70% from the first medical terminology exam
      to the third. For the 2005/2006 academic year, 61.1% of students increased their
      score above 70% from the first to the third exam. Our data indicate that students
      can achieve comprehension of medical terminology in the absence of a formal
      terminology course.

PMID- 17446650
TI  - Meat inspection education in Finnish veterinary curriculum.
AB  - This article describes the Finnish meat-inspection curriculum and presents an
      expert-panel evaluation of meat-inspection education. The work tasks of the meat
      inspection veterinarian are challenging and include classical meat inspection,
      meat hygiene, hygiene control, and animal disease and welfare. The meat
      inspection veterinarian is not only an inspector, which by itself is very
      demanding, but also an expert or "consultant" on food safety. The significant
      role of the meat-inspection veterinarian in society puts high demands on meat
      inspection education, which should provide veterinary students with sufficient
      tools to perform meat inspection and hygiene control in slaughterhouses, cutting
      premises, and further processing plants. To be of high quality, such education
      must be evaluated from time to time. An expert panel evaluated Finnish
      undergraduate meat-inspection education and found that it provides veterinary
      students with good knowledge of meat inspection. The structure of the curriculum,
      with theoretical studies followed by four weeks of practice in a slaughterhouse,
      was considered vital for learning and for creating interest in meat inspection.
      The evaluation also revealed that certain subjects should receive greater
      emphasis and some new subjects should be introduced. Hygiene-control tasks, in
      particular, have increased and should receive more emphasis in education.
      Personnel management and interaction skills should be introduced into the
      curriculum as these skills influence all the duties of the meat-inspection
      veterinarian. This article outlines the subjects to be included in the modern,
      high-quality meat-inspection curriculum recommended by the expert panel.

PMID- 17446653
TI  - An elderly patient with sarcoidosis manifesting panhypopituitarism with central
      diabetes insipidus.
AB  - We here report a 77-year-old Japanese male who suffered general fatigue with
      progressive thirst and polyuria. Central diabetes insipidus was diagnosed by
      depletion of vasopressin secretion in response to increases in serum osmolality.
      Secretory responses of anterior pituitary hormones including adrenocorticotropin,
      thyrotropin, gonadotropins and growth hormone were severely impaired. Diffuse
      swelling of the infundibulum as well as lack of T1-hyperintense signal in the
      posterior lobe was noted by pituitary magnetic resonance imaging. The presence of
      bilateral hilar lymphadenopathy and increased CD4/CD8 ratio in bronchoalveolar
      lavage fluid was diagnostic for lung sarcoidosis. Physiological doses of
      corticosteroid and thyroid hormone were administered in addition to desmopressin
      supplementation. Complete regression of the neurohypophysial swelling was notable
      two years after corticosteroid replacement. Diffuse damage of anterior pituitary
      combined with hypothalamic involvement leading to central diabetes insipidus is a
      rare manifestation in such elderly patients with neurosarcoidosis.

PMID- 17446654
TI  - Endemic goiter due to thyroglobulin gene abnormality and social ostracism.

PMID- 17446655
TI  - Identification and synergism of cis-acting elements essential for basal promoter
      activity of the human type 1 angiotensin II receptor gene in PLC-PRF-5 cells.
AB  - The basal promoter activity of the human AT(1) receptor gene was characterized
      using a human hepatoma cell line with a considerably high expression of AT(1),
      PLC-PRF-5. Four cis-acting, positively regulating elements termed AT(1)PRE1 (-113
      to -102 bp), AT(1)PRE2 (-49 to -43 bp), AT(1)PRE3 (-5 to -2 bp) and AT(1)PRE4
      (+44 to +50 bp) were identified. AT(1)PRE2 contained a GC-box-like sequence and
      bound to Sp1. AT(1)PRE1 contained two tandem GC-boxes and was bound to several
      nuclear proteins in addition to Sp1. Nuclear proteins that were bound sequence
      specifically to AT(1)PRE1, AT(1)PRE2 and AT(1)PRE4 were found in both PLC-PRF-5
      cells and 8505C cells, while those bound to AT(1)PRE3 were not found in 8505C
      cells, which showed no expression of AT(1) and almost no promoter activity for
      the AT(1) gene. Significant promoter activity was still observed even when
      AT(1)PRE1, AT(1)PRE2 and AT(1)PRE4 were all mutated. Mutagenesis of AT(1)PRE3,
      however, substantially inactivated promoter activity. AT(1)PRE1, AT(1)PRE2 and
      AT(1)PRE4 synergistically enhanced AT(1) gene transcription promoted by
      AT(1)PRE3. These results suggested that AT(1)PRE3 is responsible for the tissue
      specific expression of the human AT(1) gene, and that AT(1)PRE1, AT(1)PRE2 and
      AT(1)PRE4 function as a general enhancer in liver-derived cells.

PMID- 17446656
TI  - Long-term remission of cyclic Cushing's disease that was diagnosed and treated
      surgically in non-active phase.
AB  - Cyclic Cushing's disease is a rare clinical entity that is defined as a periodic
      excessive production of adrenocorticotropic hormone (ACTH) and cortisol. Only 42
      cases with cyclic Cushing's disease have been reported in the literature. The
      diagnosis is very difficult because of the fluctuating secretion of ACTH and
      cortisol. We report a 78-year-old woman with a pituitary adenoma presenting with
      cyclic Cushing's disease. In the present case, several interesting issues are
      pointed out: 1) MRI study detected the presence of an adenoma and selective
      venous sampling in the cavernous sinus disclosed the hypersecretion of ACTH from
      a pituitary adenoma. These neuroimaging and endocrinological studies were helpful
      for the diagnosis, even in the remission phase. 2) The disease was in the long
      term remission phase after transsphenoidal surgery despite the high recurrence
      rate in this clinical entity, although it recurred four years later. Even in the
      remission phase of cyclic Cushing's disease, meticulous endocrinological and
      neuroimaging examinations can reveal the presence of a pituitary adenoma, which
      should be treated surgically.

PMID- 17446657
TI  - Preclinical Cushing's disease characterized by massive adrenal hyperplasia and
      hormonal changes after three years of metyrapone therapy.
AB  - A 66-year-old woman had massive bilateral adrenal macronodular hyperplasia, found
      incidentally on an abdominal ultrasonogram. Her plasma ACTH and serum cortisol
      levels were normal, but they were not suppressed by low-dose dexamethasone. The
      patient did not exhibit any typical signs or symptoms of Cushing's disease. MRI
      showed no evidence of a tumor in the pituitary gland. A diagnosis of preclinical
      Cushing's disease was made, and she was treated with 11-hydroxylase inhibitor
      metyrapone. As the dose of metyrapone was increased, plasma ACTH levels gradually
      increased. After three years of treatment, she developed moon-face. Her plasma
      ACTH and serum cortisol concentrations were at their highest levels. A pituitary
      microadenoma was detected by MRI, whose source of ACTH was demonstrated by the
      definite step-up of central/peripheral ratio of ACTH obtained by cavernous sinus
      sampling. Overt Cushing's disease was diagnosed, and a pituitary tumor was
      removed by transsphenoidal surgery. In conclusion, the clinically and
      endocrinologically overt Cushing's disease characterized by macronodular adrenal
      hyperplasia was converted from a preclinical form. This case offers some insight
      into the clinical and biological features of preclinical Cushing's disease.

PMID- 17446658
TI  - Spindle formation and microtubule organization during first division in
      reconstructed rat embryos produced by somatic cell nuclear transfer.
AB  - The present study was conducted to demonstrate the spindle formation and behavior
      of chromosomes and microtubules during first division in reconstructed rat
      embryos produced by somatic cell nuclear transfer (SCNT) with cumulus cell
      nuclei. To demonstrate the effect of oocyte aging after ovulation on the cleavage
      of SCNT embryos, micromanipulation was carried out 11, 15 and 18 h after
      injection of hCG. SCNT oocytes were activated by incubation in culture medium
      supplemented with 5 microM ionomycin for 5 min followed by treatment with 2 mM 6
      dimethylaminopurine (6-DMAP) in mR1ECM for 2-3 h. For immunocytochemical
      observation, the SCNT embryos were incubated with monoclonal anti-alpha-tubulin
      antibody and then fluorescein isothiocyanate (FITC)-conjugated goat anti-mouse
      IgG. Cleavage rates were significantly higher for oocytes collected after 15 and
      18 h rather than for those collected 11 h after injection of hCG (56 and 53%,
      respectively vs. 28%; P<0.05). Premature chromosome condensation occurred before
      activation of the SCNT oocytes, but adequate spindle formation was only rarely
      observed. The distribution of microtubules in SCNT embryos after activation was
      different from those of fertilized and parthenogenic oocytes, i.e., a dense
      microtubule organization shaped like a ring was observed. Eighteen to 20 h post
      activation, most SCNT embryos were in the 2-cell stage, but no nucleoli were
      clearly visible, which was quite different from the fertilized oocytes. In
      addition, first division with and without small cellular bodies containing DNA
      was observed in the rat SCNT embryos in some cases. The present study suggests
      that reorganization of transferred nuclei in rat SCNT embryos may be inadequate
      in terms of formation of the mitotic assembly and nucleolar reorganization.

PMID- 17446659
TI  - Donor cell lines considerably affect the outcome of somatic nuclear transfer in
      the case of bovines.
AB  - Since the first successful nuclear transfer (NT) experiments were carried out,
      various somatic cell types have been used as donor cells for production of cloned
      animals. In most experiments, fibroblasts are used since they only need to be
      isolated and cultivated. Recently, some researchers have shown that different
      cell cultures from different sources possess different capacities to support
      preimplantation development of NT embryos. The blastocyst rates obtained in our
      previous studies varied and were as high as 45% in relation to the number of
      reconstructed embryos. This led us to question whether the origin and culture
      conditions of the defined male and female fibroblast lines could be responsible
      for the differences in developmental potency. Taking all our results into
      consideration, we conclude that different fibroblast lines recovered from the
      same tissue and cultivated under equal culture conditions could produce
      dramatically different blastocyst rates. The influence of cell line itself is
      higher than the influence of passage number. The observed effects of cell cycle
      stage, chromosomal aberrations, and diminished vitality are important but not
      sufficient to discriminate well-qualified nuclear donor cells. We speculate that
      some epigenetically regulated deviations in the gene expression program are
      responsible for these phenomena. Explanation of the underlying mechanisms should
      contribute to better understanding of epigenetic reprogramming and may ultimately
      assist reprogramming in the laboratory.

PMID- 17446660
TI  - Ovsynch plus CIDR protocol for timed embryo transfer in suckled postpartum
      Japanese Black beef cows.
AB  - We compared synchronization and pregnancy rates, and the increase in blood
      progesterone concentrations during luteal development, between (1) Ovsynch plus
      an intravaginal controlled internal drug release (CIDR) device protocol followed
      by timed embryo transfer (timed ET), and (2) a conventional estrus
      synchronization method using PGF(2 alpha) and ET in suckled postpartum Japanese
      Black beef cows. Cows in the PGF group (n=18) received a PGF(2 alpha) analogue
      when a CL was first palpated per rectum at 10-d intervals after 1 to 2 month
      postpartum. Cows (n=11), which showed estrus (Day 0) within 5 d of the PGF(2
      alpha), and had a CL on Day 7, received ET. Cows in the Ovsynch+CIDR group (n=19)
      underwent the Ovsynch protocol plus a CIDR for 7 d (GnRH analogue and CIDR on Day
      9, PGF(2alpha) analogue with CIDR removal on Day-2, and GnRH analogue on Day 0),
      with ET on Day 7. The ovulation synchronization (100%) and embryo transfer (100%)
      rates in the Ovsynch+CIDR group were greater (P<0.01) than the estrus
      synchronization (66.7%) and the embryo transfer (61.1%) rates in the PGF group.
      The postpartum interval at ET in the Ovsynch+CIDR group (62.5 +/- 2.5 d) was
      shorter (P<0.01) than in the PGF group (74.9 +/- 3.9 d). The pregnancy rate in
      the Ovsynch+CIDR group (57.9%) did not differ significantly from that in the PGF
      group (50.0%). Plasma progesterone concentrations were not significantly
      different in the two groups on Days 0, 1, 2, 5, 7, 14 and 21. In summary, higher
      synchronization and transfer rates, and shorter postpartum interval to ET, can be
      achieved with timed ET following the Ovsynch plus CIDR protocol than after estrus
      with the single PGF(2 alpha) treatment followed by ET in suckled postpartum
      recipient beef cows. Pregnancy rates were similar. Also, the increase in blood
      progesterone concentrations during luteal development following ovulation
      synchronized by the Ovsynch plus CIDR protocol was similar to that after estrus
      induced by the PGF(2 alpha) treatment.

PMID- 17446661
TI  - Approaches to driving the evolving understanding of lower oesophageal sphincter
      mechanical function.
AB  - This article reviews and places into context the development of lower oesophageal
      sphincter (LOS) manometry, the key technique for researching the mechanics of
      this region. The first of two major challenges, being able to record sphincter
      pressure accurately with generally available equipment, was solved by the advent
      of perfused manometry in the 1960s. The other main challenge was to achieve
      reliable, continuous recording of LOS pressure, despite the constant movements of
      the LOS relative to the manometric catheter. Though well documented, this
      challenge is still poorly understood and prioritised, as many clinical/diagnostic
      and research manometric studies use methods for LOS manometry that are
      invalidated by LOS movement. There are two techniques that can record
      continuously from the LOS, despite its movements: high resolution manometry
      (HRM), which uses multiple point pressure sensors spaced at 1 cm interval or
      less, and the sleeve, which is a single long sensor. HRM provides valuable
      additional information on the varied topography of pressure patterns across the
      gastro-oesophageal junction and how this can change in an individual, second to
      second. HRM especially, but also sleeve manometry continue to advance
      understanding of the mechanics of gastro-oesophageal reflux, to unravel the
      mysteries of the mechanics of hiatus hernia and the diaphragmatic hiatus, to
      define why antireflux surgery fails or causes dysphagia, to recognise patients
      with dysphagia due to isolated defects of LOS relaxation and to test novel
      therapies for reflux disease directed at LOS function. Ample evidence now exists
      that accurate monitoring of LOS and gastro-oesophageal junction pressures is
      important for the diagnostic assessment of many patients and for advancing
      research into several aspects of the mechanical function of the LOS and its
      surrounding structures. This evidence now needs to be better reflected in the
      methods used for routine clinical practice and research.

PMID- 17446662
TI  - Mechanisms of the inhibitory effects of a phenoxazine compound, 2-amino-4,4 alpha
      dihydro-4 alpha-7-dimethyl-3H-phenoxazine-3-one, on the contraction of the smooth
      muscle of the guinea pig taenia cecum.
AB  - To elucidate the mechanisms involved in the relaxing effect of 2-amino-4, 4alpha
      dihydro-4alpha-7-dimethyl-3H-phenoxazine-3-one (Phx-1) on smooth muscle, we
      investigated its effects on the contraction of both intact and skinned (cell
      membrane permeabilized) preparations from the guinea pig taenia cecum. In intact
      preparations, Phx-1 concentration-dependently suppressed the contraction induced
      by either acetylcholine (ACh) or high-K(+) with an IC(50) value estimated at
      around 100 muM. Similar inhibitory actions of Phx-1 on force were observed in
      intracellular Ca store depleted preparations. In cell membrane depolarized
      preparations in the absence of extracellular Ca, however, Phx-1 had little effect
      on either caffeine- or ACh-induced contractions. In skinned preparations, Phx-1
      suppressed Ca(2+)-induced contractions at concentrations higher than 100 muM.
      These results suggest that inhibition of smooth muscle contraction by Phx-1 is
      due mainly to inhibition of Ca(2+)-influx, although Phx-1 also seems to have
      direct inhibitory effects on the activities of the contractile apparatus.

PMID- 17446663
TI  - Extracirculatory effects of noise of various frequency spectra in humans--effect
      of pink and blue noise on gastric myoelectrical activity and gastrointestinal
      passage of nutrients.
AB  - Recent investigations in humans point out to a disturbing effect of auditory
      stimuli on the functional integrity of the brain-gut axis. The study was devoted
      to a systematic comparative evaluation of the effect of noises of different
      frequency spectra on the postprandial electrical and transport functions of the
      digestive tract in humans. Twenty six healthy subjects attended a cross-over
      study, which aimed at comparison of the effect of pink contrasted to blue noise
      within a given category (band or tonal) and a meal stimulus type (semi-liquid or
      solid test meal). A panel of noninvasive measurement methods was applied: heart
      rate variability (HRV) analysis, surface electrogastrography, (13)CO(2) breath
      tests for gastric emptying (GE), lactulose hydrogen breath test for orocecal
      transit time (OCTT). The blue tonal noise was rated the most annoying one,
      whereas solely the pink noises exerted discernible cardiovascular effects. No one
      of the four noises was capable of overriding the meal-induced preponderance of
      the sympathetic tone. The postprandial gastric myoelectrical activity and the GE
      of either the semiliquid or the solid test meal appeared to be ;resistant' to the
      noise exposure, irrespective of the noise type. Similar was the finding in the
      case of the OCTT, with the exception of a statistically significant retardation
      of the OCTT with the blue band noise. Ingestion of mixed caloric meals seems to
      elicit a protective influence against noise-elicited derangements of the
      functional integrity of the digestive tract proven formerly to occur during the
      fasting period.

PMID- 17446664
TI  - [Host factors and their relevance to virus infection in plants].
AB  - Virus infection is established when viral proteins can interact with host factors
      to execute replication and/or cell-to-cell movement. Even after the virus
      infection has started, host resistance reactions, if trigged, would suppress
      further virus propagation. We would like to introduce what we understand about
      host factors as determinants of infection establishment and as key resistance
      molecules. Genome-wide information of Arabidopsis is providing us much
      information about such host factors involved in virus infection.

PMID- 17446665
TI  - [Cell entry mechanism of coronaviruses: implication in their pathogenesis].
AB  - Coronaviruses infect many species of animals, including humans. Among them,
      murine coronavirus, mouse hepatitis virus (MHV) has been well studied as a model
      of human diseases, such as hepatitis and demyelinating disease. An agent causing
      severe acute respiratory disease (SARS), SARS coronavirus (SARS-CoV), is a
      newcomer in this genus, however, it is now one of the most studied coronaviruses
      due to its medical impact. The receptors of those two viruses have been
      identified and their cell entry mechanism has been actively investigated.
      Recently, SARS-CoV cell entry mechanism is shown to be different from that of
      other enveloped viruses, including MHV. In this review, cell entry mechanism of
      those two viruses is described, stressing on the difference and similarity found
      between those two viruses.

PMID- 17446667
TI  - [Establishment of a reverse genetics system for rotavirus].
AB  - The rotavirus genome is composed of 11 segments of double-stranded RNA (dsRNA).
      Rotavirus is the leading etiological agent of severe gastroenteritis in infants
      and young children worldwide. Reverse genetics is the powerful and ideal
      methodology for the molecular study of virus replication, which enables the virus
      genome to be artificially manipulated. Very recently, we developed the first
      reverse genetics system for rotavirus, which enables one to generate an
      infectious rotavirus containing a novel gene segment derived from cDNA. In this
      review, we describe each steps of rotavirus replication to understand the
      background to the establishment of a reverse genetics system for rotavirus, and
      summarize the reverse genetics systems for segmented dsRNA viruses including
      rotavirus.

PMID- 17446666
TI  - [Human metapneumovirus].
AB  - Human metapneumovirus (hMPV), first isolated in the Netherlands in 2001, is a
      member of the genus Metapneumovirus of the sub-family Pneumovirinae of the family
      Paramyxoviridae. The genomic organization of hMPV is 3'-N-P-M-F-M2-SH-G-L-5'.
      hMPV resembles the sole member of this genus, avian pneumovirus. hMPV is the most
      closely related human pathogen to respiratory syncytial virus. Phylogenetic
      analysis of the nucleotide sequences indicated that there were two genetic
      groups. Furthermore, each group could be subdivided into two subgroups. hMPV
      encodes three surface proteins, F, G and SH proteins. The majority of antibodies
      to hMPV in serum were antibody against F protein, which mediates cross-group
      neutralization and protection. The incidences of hMPV-associated respiratory
      infection estimate 5 to 10% in children and 2 to 4% in adults. hMPV generally
      causes upper respiratory tract infection and flu-like illness, the virus can be
      associated with lower tract infections, such as wheezy bronchitis, bronchitis,
      bronchiolitis and pneumonia, in very young children, elderly persons, and
      immunocompromised patients. hMPV has a seasonal peak during the spring in Japan.
      Reinfection with hMPV frequently occurs in children, implying that the host
      immune response induced by natural infection provides incomplete protection. The
      RT-PCR test is the most sensitive test for detection of hMPV.

PMID- 17446668
TI  - [Biological safety in virological field with special considerations on class II
      biological safety cabinets].
AB  - The most critical point for the biosafety is not sophisticated devices or
      facilities, but education of workers and their compliance to the regulation.
      Appropriate devices should be carefully selected in the introduction of new
      devices, and they should be properly maintained. The class II biosafety cabinet
      is one of the delicate safety equipments. It should be kept adequately maintained
      throughout the lifetime of the cabinet to insure safety of the laboratory. For
      the maintenance, appropriate measuring equipments should be used by trained
      technicians. The recently enforced law for control of recombinant DNA researches
      should be applied for the handling of pathogens even in non-recombinant DNA
      researches after proper modifications.

PMID- 17446669
TI  - [Mechanisms of EBV-mediated oncogenesis].
AB  - Epstein-Barr virus (EBV) is the DNA tumor virus, which is known to be relevant to
      various cancers. EBV maintains latent infection in cancer cells, and there are
      three types of latent infection (type I-III) according to the patterns of viral
      latent genes expression. EBV has the ability to transform B cells into
      immortalized lymphoblastoid cell lines (LCL) showing type III latency, in which
      all latent genes are expressed. The mechanism of B-cell transformation has
      provided a model of EBV-associated lymphomas in immunosuppressed individuals. In
      type I and II latency, the limited numbers of latent genes are expressed.
      Previous studies have demonstrated the oncogenic functions of latent EBV genes
      including nuclear antigen EBNA1, membrane protein LMP1 and LMP2A. In addition, we
      have demonstrated that EBV-encoded small RNA EBERs play a significant role in
      oncogenesis. Here we summarize recent progresses in the studies on molecular
      mechanisms of EBV-mediated oncogenesis.

PMID- 17446670
TI  - [Kaposi's sarcoma-associated herpesvirus and mechanisms of oncogenesis].
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV, also known as human herpesvirus
      8), is well known to be responsible for Kaposi's sarcoma, the most common AIDS
      related cancer. KSHV is also associated with the B cell malignancies primary
      effusion lymphoma and multicentric Castleman's disease. Cellular signaling
      pathways regulate the proliferation and differentiation during normal development
      and a small number of signaling pathways are involved in tumors. KSHV utilize
      those pathways, such as pRb-E2F, Wnt and Notch pathways, to promote driving of
      cell cycle and to regulate their own life-cycles (i.e., latency and lytic cycle).
      This review focuses on signaling pathways which KSHV gene products manipulate and
      discusses their contributions to tomorigenesis and regulation of viral life
      cycles.

PMID- 17446671
TI  - [Human papillomavirus and cervical cancer].
AB  - Human papillomavirus (HPV) is a small non-enveloped icosahedral virus with a
      circular double-stranded DNA genome of 8 kilo base pairs. HPV particles reach and
      infect the basal cells of the stratified epithelia through small epithelial
      lesions. In the basal cells the viral DNA is maintained as episomes, which start
      to replicate when the host cells initiate terminal differentiation. In these
      differentiating cells the degradation of p53 by the E6 protein and the abrogation
      of the pRb functions by the E7 protein lead to the reactivation of the DNA
      synthesis machinery. After virus propagation the host cells usually die. On the
      other hand, in some of the infected cells, the E6 and E7 genes are integrated on
      rare occasion into cell DNA. The cell continuously expressing the E6 and E7
      proteins from the integrated genes is immortalized and sometimes acquires
      malignant phenotype induced by the accumulated damages to DNA. Of more than 100
      HPV genotypes recorded to date, 13 including types 16 and 18 are associated with
      cervical cancer. Expression of HPV major capsid protein L1 in some cultured cells
      results in production of virus-like particles (VLPs). The VLPs of types 6, 11,
      16, and 18 were used as a prophylactic vaccine in recent clinical trials and
      shown to successfully induce type-specific neutralizing antibodies in the
      recipients.

PMID- 17446672
TI  - [Pathogenesis of the hepatocellular carcinoma associated with hepatitis C virus].
AB  - Hepatitis C virus (HCV) is known as one of major causative agents of
      hepatocellular carcinoma (HCC) in the world. The pathogenesis of HCC associated
      with HCV, however, has not been fully elucidated yet, although the chronic
      inflammation induced by HCV infection is considered to contribute greatly to the
      HCC development. Some HCV gene products have been shown to possess transformation
      activities in cultured cells. Several oncogenic signal pathways in the cells were
      modulated by the exogenous expression of the HCV proteins. A few lines of the
      transgenic mice producing the core protein among those products was also reported
      to develop liver steatosis and HCC without apparent inflammation after rearing
      for a relatively long period. So, the functions of the core on the modulation of
      cellular events have been extensively examined and characterized. Here, I would
      summarize the progress of the research for the pathogenesis of HCC associated
      with HCV.

PMID- 17446673
TI  - [HTLV-I and leukemogenesis].
AB  - Human T-cell leukemia virus type I (HTLV-I) is a causative virus of adult T-cell
      leukemia (ATL). ATL is a highly aggressive neoplastic disease of CD4 positive T
      lymphocyte, which is featured by the pleomorphic tumor cells with hypersegmented
      nuclei, called " flower cell". HTLV-I increases its copy number by clonal
      proliferation of the host cells, not by replication of the virus. Therefore, HTLV
      I eventually induces ATL. Tax, encoded by HTLV-I pX region, has been recognized
      as a protein that plays a central role of the transformation of HTLV-I-infected
      cells by its pleiotropic actions. However, fresh ATL cells frequently lose Tax
      protein expression by several mechanisms. Recently, HBZ was identified in the
      complementary strand of HTLV-I and it is suggested that HBZ is a critical gene in
      leukemogenesis. Furthermore, there is a long latency period before onset of ATL,
      indicating the multistep mechanisms of leukemogenesis. Therefore, it is suggested
      that multiple factors, such as viral proteins, genetic and epigenetic changes of
      host genome, and immune status of the hosts, could be implicated in
      leukemogenesis of ATL.

PMID- 17446674
TI  - Characterization of the inhabitancy of mouse intestinal bacteria (MIB) in rodents
      and humans by real-time PCR with group-specific primers.
AB  - Mouse intestinal bacteria (MIB) is a new operational taxonomic unit (OTU)
      belonging to the Bacteroides subgroup in the Cytophaga-Flavobacter-Bacteroides
      (CFB) phylum recently found in the intestine of mice, rats and humans. However,
      their characters are still unknown since they have not yet been isolated by
      culture. To understand their habitat characteristics in intestinal tracts, the
      quantification assays of MIB were established using MIB group-specific primers.
      The MIB population in the intestine was evaluated as a percentage of the number
      of 16S rRNA gene copy of MIB. A real-time PCR assay using group specific primers
      showed the fluctuation of MIB inhabitancy and revealed that the MIB population in
      the small intestine of mice was significantly lower than the large intestinal
      contents. Moreover, MIB was found in human feces though the number was lower than
      in murine. This assay using group-specific primers revealed new information about
      host-preference of MIB.

PMID- 17446675
TI  - Molecular survey of Babesia microti, Ehrlichia species and Candidatus
      neoehrlichia mikurensis in wild rodents from Shimane Prefecture, Japan.
AB  - A significant number of patients are diagnosed with "fevers of unknown origin"
      (FUO) in Shimane Prefecture in Japan where tick-borne diseases are endemic. We
      conducted molecular surveys for Babesia microti, Ehrlichia species, and
      Candidatus Neoehrlichia mikurensis in 62 FUO cases and 62 wild rodents from
      Shimane Prefecture, Japan. PCR using primers specific for the Babesia 18S small
      subunit rRNA (rDNA) gene and Anaplasmataceae groESL amplified products from 45%
      (28/62) and 25.8% (16/62) of captured mice, respectively. Of the 28 18S rDNA PCR
      positives, 23 and five samples were positive for Hobetsu- and Kobe-type B.
      microti, respectively. In contrast, of the 16 groESL PCR positives, eight, one
      and seven samples were positive for Ehrlichia muris, Ehrlichia sp. HF565 and
      Candidatus N. mikurensis, respectively. Inoculation of selected blood samples
      into Golden Syrian hamsters indicated the presence of Hobetsu- and Kobe-type B.
      microti in four and one sample, respectively. Isolation of the latter strain was
      considered important as previous studies suggested that the distribution of this
      type was so far confined to Awaji Island in Hyogo Prefecture, where the first
      case of transfusion-associated human babesiosis originated. DNA samples from 62
      FUO human cases tested negative for B. microti 18S rDNA gene, Anaplasmataceae
      groESL gene, Rickettsia japonica 17K genus-common antigen gene and Orientia
      tsutsugamushi 56K antigen gene by PCRs. We also conducted seroepidemiological
      surveys on 62 human sera collected in Shimane Prefecture from the FUO patients
      who were suspected of carrying tick-borne diseases. However, indirect
      immunofluorescent antibody tests using B. microti- and E. muris-infected cells
      detected IgG against E. muris in only a single positive sample. This study
      demonstrates the presence of several potentially important tick-borne pathogens
      in Shimane Prefecture and suggests the need for further study on the causative
      agents of FUOs.

PMID- 17446676
TI  - Biofilm acts as a microenvironment for plankton-associated Vibrio cholerae in the
      aquatic environment of Bangladesh.
AB  - The role of biofilm as a microenvironment of plankton-associated Vibrio cholerae
      was investigated using plexiglass as a bait. A total of 72 biofilm samples were
      tested using culture, direct fluorescent antibody (DFA) and molecular techniques
      following standard procedures. Culturable V. cholerae (smooth and rugose
      variants) were isolated from 33% of the samples. V. cholerae O1 were detected by
      FA technique throughout the year except April and June. All V. cholerae O1
      isolates were positive for tcpA, ctxA and ace genes while V. cholerae non-O1, non
      O139 isolates lacked these genes. V. cholerae O1 (both Inaba and Ogawa) strains
      had identical ribotype pattern (R1), but V. cholerae non-O1, non-O139 had
      different ribotype patterns. All V. cholerae O1 strains were resistant to vibrio
      static compound (O/129). All V. cholerae O1 except one were resistant to
      trimethoprime-sulphamethoxazole, streptomycin, nalidixic acid and furazolidone
      but sensitive to ciprofloxacin, and tetracycline. This study indicates that
      plexiglass can act as a bait to form biofilm, a microenvironment that provides
      shelter for plankton containing V. cholerae in the aquatic environment of
      Bangladesh.

PMID- 17446677
TI  - Detection of enterotoxin and toxic shock syndrome toxin 1 genes in
      Staphylococcus, with emphasis on coagulase-negative staphylococci.
AB  - The detection of staphylococcal enterotoxins is decisive for the confirmation of
      an outbreak and for the determination of the enterotoxigenicity of strains. Since
      the recognition of their antigenicity, a large number of serological methods for
      the detection of enterotoxins in food and culture media have been proposed. Since
      immunological methods require detectable amounts of toxin, molecular biology
      techniques represent important tools in the microbiology laboratory. In the
      present study, polymerase chain reaction (PCR) was used to identify genes
      responsible for the production of enterotoxins and toxic shock syndrome toxin 1
      (TSST-1) in S. aureus and coagulase-negative staphylococci (CNS) isolated from
      patients and the results were compared with those obtained by the reverse passive
      latex agglutination (RPLA) assay. PCR detection of toxin genes revealed a higher
      percentage of toxigenic S. aureus strains (46.7%) than the RPLA method (38.3%).
      Analysis of the toxigenic profile of CNS strains showed that 26.7% of the
      isolates produced some type of toxin, and one or more toxin-specific genes were
      detected in 40% of the isolates. These results suggests the need for further
      studies in order to better characterize the pathogenic potential of CNS and
      indicate that attention should be paid to the toxigenic capacity of this group of
      microorganisms.

PMID- 17446678
TI  - Production of shiga toxin by a luxS mutant of Escherichia coli O157:H7 in vivo
      and in vitro.
AB  - Quorum sensing is a type of bacterial communication mediated by chemical
      signaling molecules called autoinducers (AIs). The production of AI-2 and AI-3 is
      dependent on the luxS gene in Escherichia coli O157:H7. A luxS mutation caused a
      minimal decrease (about 2-fold) in Shiga toxin (Stx) production in in vitro
      cultures using Luria-Bertani broth. The effect of a luxS mutation on the
      virulence of E. coli O157:H7 was examined by using germfree mice. There were no
      differences between the luxS mutant and the wild-type in the bacterial counts in
      feces shedding, Stx production, or the survival of the mice. The treatment of
      ciprofloxacin decreased the bacteria in feces but increased the Stx production.
      However, even treatment with ciprofloxacin did not make any difference between
      the luxS mutant and the wild-type in animal experiments.

PMID- 17446679
TI  - Isolation and characterization of virulent yellowtail ascites virus.
AB  - Yellowtail ascites virus (YTAV) is the causative agent of ascites and deformity
      in fish and causes serious losses to the fish-farming industry of yellowtail fry
      and fingerling Seriola quinqueradiata in Japan. In 2006, cultured yellowtail died
      from ascites in Kochi, Japan. We isolated and characterized a virus from the
      diseased fish. Based on the pathogenicity, culture characteristics, morphological
      features, RT-PCR results targeting VP2/NS region, phylogeny based on the VP1
      amino acid sequence, and immunochemical reactivity of structural proteins, the
      virus isolate was identified as YTAV (designated as YTAV-06). YTAV-06 was a more
      virulent isolate than YTAV Y-6, isolated originally from yellowtail with ascites.
      To our knowledge, this is the first report describing that YTAV isolates may vary
      in their virulence.

PMID- 17446680
TI  - Gene expression profiling of polymorphonuclear leukocytes treated with the
      culture filtrate of Aspergillus fumigatus and gliotoxin.
AB  - Pathogens of the Aspergillus species are frequently seen in deep-seated mycoses.
      We previously demonstrated that the culture filtrate of Aspergillus fumigatus
      (CF) has immunosuppressive effects on polymorphonuclear leukocytes (PMNs), which
      act as the main phagocytes to hyphae of Aspergillus fumigatus (A. fumigatus). But
      little is known about the gene expression profiles involved in it. Therefore we
      investigated the changes in gene expression in human PMNs treated with CF or
      gliotoxin at two time points, using microarray analysis. CF and gliotoxin changed
      the expression of 548 and 381 genes, respectively. Only 51 genes showed the same
      expression patterns with the two stimulants, and CF-induced changes in gene
      expression occurred comparatively earlier than those induced by gliotoxin. Among
      31 genes encoding apoptosis, which were up- or down-regulated in this assay, only
      3 genes were similarly changed by both kinds of stimulation. Apoptosis was
      detected and quantified using two apoptosis assays. CF and gliotoxin changed the
      expessions of only 3 out of 19 regulated genes related to inflammatory mediators
      and receptors similarly. The up-regulation of the gene encoding annexin 1
      (ANXA1), which is known to be involved in extravasation and apoptosis of
      neutrophils, may play a role in the immunosuppressive effect of A. fumigatus. The
      difference in expression changes between CF and gliotoxin is presumed to be
      caused by the interaction among the components of CF and therefore the
      interaction is an area of interest for further investigation.

PMID- 17446681
TI  - Pro- and anti-inflammatory cytokines produced by human monocytes challenged in
      vitro with Paracoccidioides brasiliensis.
AB  - Monocytes and macrophages play a central role in innate and adaptive immune
      response against systemic fungal infections. Imbalances in suppressor or
      stimulatory cytokine secretion caused by these cells may influence disease
      development, microorganism death, and the nature of the adaptive immune response.
      This study analyzed the monocyte cytokine profiles of healthy individuals
      challenged with high and low virulent strains of P. brasiliensis and mRNA
      cytokine expression kinetics by reverse transcription polymerase chain reaction
      (RT-PCR). Peripheral blood monocytes from healthy volunteers were cultured in
      vitro with and without virulent (Pb18) or low virulence (Pb265) strains from P.
      brasiliensis viable yeast cells. Interleukin-1 beta (IL-1beta), IL-6, IL-8, IL
      10, tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta
      (TGF-beta1) were measured in culture supernatants by enzyme immunoassay (ELISA),
      and mRNA cytokine expression was determined by RT-PCR at 0, 4, 8, 12, 18 and 48
      hr. Both P. brasiliensis strains induced monocyte production of IL-1beta, IL-6,
      IL-10 and TNF-alpha. Pb18 induced higher levels of IL-1beta, IL-6, and IL-10 than
      Pb265. IL-8 and TGF-beta1 levels were not significantly different from those
      cultured without stimulus. The mRNA cytokine expression was similar to
      supernatant cytokines measured by ELISA. In vitro monocyte challenge with
      virulent P. brasiliensis strain induces earlier and higher levels of pro- and
      anti-inflammatory cytokines than low virulence strain.

PMID- 17446682
TI  - Distinct function of Pseudomonas aeruginosa type IV pili disclosed in the
      bacterial pass-through of membrane filter with smaller pore sizes.
AB  - Membrane filter pass-through ability of Pseudomonas aeruginosa was analyzed with
      isogenic mutants. A flagellum-deficient fliC mutant required two-times longer
      time (12 hr) to pass through a 0.45-microm pore size filter. With 0.3- and 0.22
      microm filters, however, the fliC mutant showed no remarkable disability.
      Meanwhile a pilA mutant defective in twitching motility failed to pass through
      the 0.22-microm filter. Complementation of the mutant with pilA gene on a plasmid
      restored the twitching motility and the 0.22-microm filter pass-through activity.
      Thus, the distinctive role of P. aeruginosa type IV pili in infiltration into
      finer reticulate structures was indicated.

PMID- 17446683
TI  - Cytolethal distending toxin (Cdt)-producing escherichia coli isolated from a
      child with bloody diarrhea in Japan.
AB  - In a retrospective analysis by PCR, the cdtI gene encoding the cytolethal
      distending toxin (Cdt) was detected in Escherichia coli O2:H12 strain isolated
      from the bloody diarrheal stool specimen of a child. To our knowledge, this is
      the first report showing the possible association of Cdt-producing E. coli in
      Japan, particularly in a child with bloody diarrhea.

PMID- 17446684
TI  - Increased inhibitory capacity of an anti-C5a complementary peptide following
      acetylation of N-terminal alanine.
AB  - Amino acids 37 to 53 (RAARISLGPRCIKAFTE) of C5a anaphylatoxin form an essential
      region for C5a function. To target this sequence, we generated a complementary
      peptide (ASGAPAPGPAGPLRPMF) designated PepA which has a potent inhibitory effect
      on C5a activity. By introducing an acetyl group at the N-terminal alanine of
      PepA, an acetylated form was generated which was designated AcPepA. The
      acetylation resulted in increased inhibition of C5a stimulation of neutrophils as
      determined by Ca influx. Furthermore, AcPepA partially inhibited the lethal shock
      induced in mice by intravenous administration of Candida albicans water-soluble
      mannoprotein-beta-glucan complex. In addition, local skin inflammation in rats
      caused by an anti-Crry monoclonal antibody was suppressed when AcPepA and the
      antibody were injected together, while PepA had little inhibitory capacity. The
      potent inhibitory capacity of AcPepA was also confirmed by a skin reaction of
      guinea pigs inoculated with recombinant human C5a together with AcPepA.

PMID- 17446685
TI  - C terminal half fragment (50 kDa) of heavy chain components of Clostridium
      botulinum type C and D neurotoxins can be used as an effective vaccine.
AB  - Recombinant whole heavy chains (H, 100 kDa) and their N-terminal (Hn, 50 kDa) and
      C-terminal (Hc, 50 kDa) half fragments of Clostridium botulinum type C and D
      neurotoxins were expressed as glutathione S-transferase (GST) fusion proteins in
      Escherichia coli. GST eliminated-preparations of H (10 microg), Hn (5 microg), Hc
      (5 microg), or a mixture of Hn (5 microg) and Hc (5 microg) of types C and D were
      mixed with an equal volume of adjuvant, and then were twice injected into mice
      subcutaneously. After immunization, the mice were challenged with up to 10(6) the
      minimum lethal doses (MLD)/0.5 ml of C or D toxin, the type of which was same as
      that of the immunogens. All of the mice immunized with antigens except for Hn
      survived against 10(5) to 10(6) MLD/0.5 ml of the toxins, but the mice immunized
      with Hn were killed by 100 MLD/0.5 ml. The mice immunized with a mixture of C-Hc
      and D-Hc, each 5 microg, also showed a high level of resistance against both C
      and D toxins. Antibody levels immunized with GST fused-or GST
      eliminatedpreparation were quite similar. These results indicate that recombinant
      GST-fused Hc can be used as a safe and effective vaccine for type C and D
      botulism in animals. It also became clear that one time inoculation with a large
      amount of C-Hc or D-Hc, 100 microg, is useful for vaccine trials in mice.

PMID- 17446686
TI  - Serum withdrawal-induced apoptosis in ZrchI prion protein (PrP) gene-deficient
      neuronal cell line is suppressed by PrP, independent of Doppel.
AB  - Previous studies have shown that cellular prion protein (PrP(C)) plays anti
      apoptotic and antioxidative role against cell death induced by serum-deprivation
      (SDP) in an immortalized prion protein gene-deficient neuronal cell line derived
      from Rikn prion protein (PrP) gene-deficient (Prnp(-/-)) mice, which ectopically
      produce excess Doppel (Dpl) (PrP-like glycoprotein). To investigate whether
      PrP(C) inhibits apoptotic neuronal cell death without Dpl, an immortalized cell
      line was established from the brain of ZrchI Prnp(-/-) mice, which do not show
      ectopic expression of Dpl. The results using a ZrchI neuronal Prnp(-/-) cell line
      (NpL2) showed that PrP(C) potently inhibited SDP-induced apoptotic cell death.
      Furthermore, PrP(C) expression enhanced the superoxide dismutase (SOD) activity
      in NpL2 cells. These results indicate that Dpl production did not affect anti
      apoptotic and anti-oxidative functions of PrP, suggesting that PrP(C) may be
      directly correlated with protection against oxidative stress.

PMID- 17446687
TI  - The potent antibacterial activity of Sitafloxacin against fluoroquinolone
      resistant clinical isolates of Vibrio cholerae O1.
AB  - The in vitro antibacterial activity of sitafloxacin using clinical isolates of
      Vibrio cholerae O1 was compared to other fluoroquinolones: ciprofloxacin,
      ofloxacin, sparfloxacin and levofloxacin. Against fluoroquinolone-resistant O1
      strains, sitafloxacin was 4- to 16-fold more effective than other
      fluoroquinolones at MIC(90*). Against fluoroquinolone-susceptible O1 strains, the
      MIC(90) of sitafloxacin was 2- to 4-fold lower than other fluoroquinolones. This
      suggests sitafloxacin can be used in the treatment of infections caused by V.
      cholerae O1 strains including the fluoroquinolone-resistant strains.

PMID- 17446688
TI  - Prediction of efficient virological response to pegylated interferon/ribavirin
      combination therapy by NS5A sequences of hepatitis C virus and anti-NS5A
      antibodies in pre-treatment sera.
AB  - A considerable number of patients infected with Hepatitis C virus subtype 1b (HCV
      1b) do not respond to pegylated interferon/ribavirin combination therapy. In this
      study we explored a useful factor(s) to predict treatment outcome. A total of 47
      HCV-1b-infected patients were treated with pegylated interferon/ ribavirin for 48
      weeks. Sera of the patients were examined for the entire NS5A sequence of the HCV
      genome, HCV RNA titers and anti-NS5A antibodies. According to their responses,
      the patients were divided into two groups, early viral responders who cleared the
      virus by week 16 (EVR[16w]) and those who did not (Non-EVR[16w]). The mean number
      of mutations in the V3 region (aa 2356 to 2379) or that in the V3 region plus its
      N-terminally flanking region, which we refer to as interferon/ribavirin
      resistancedetermining region (IRRDR; aa 2334 to 2379), of NS5A obtained from the
      pretreatment sera was signifi-cantly larger for EVR(16w) compared with Non
      EVR(16w). Moreover, HCV-1b isolates with > or =5 mutations in V3 or those with >
      or =6 mutations in IRRDR were almost exclusively found in EVR(16w). Also, the
      presence of detectable levels of anti-NS5A antibodies in the pretreatment sera
      was closely associated with EVR(16w). In conclusion, a high degree of sequence
      variation in V3 (> or =5) or IRRDR (> or =6) and the presence of detectable
      levels of anti-NS5A antibodies in the pretreatment sera would be useful factors
      to predict EVR(16w). On the other hand, a less diverse sequence in V3 (< or =4)
      or IRRDR (< or =5) together with the absence of detectable anti-NS5A antibodies
      could be a predictive factor for Non-EVR(16w).

PMID- 17446689
TI  - Two new antifungal alkaloids produced by Streptoverticillium morookaense.
AB  - A new carbazole alkaloid, streptoverticillin, and a new 2-azetidinone,
      streptoverticillinone, along with three known cyclodipeptides were isolated from
      the mycelial solid culture of Streptoverticillium morookaense. Their structures
      were elucidated by analysis of 1D and 2D NMR, mass spectra and optical rotation
      data. Two new compounds exhibited antifungal activity against Peronophythora
      litchii.

PMID- 17446690
TI  - SPF-5506-A4, a new peptaibol inhibitor of amyloid beta-peptide formation produced
      by Trichoderma sp.
AB  - A new peptaibol compound, SPF-5506-A4, was isolated from the fermentation broth
      of Trichoderma sp. SPF-5506. The chemical structure of the 14-residue peptide was
      determined by MS, NMR and amino acid sequence analyses. The absolute
      configuration of amino acid residues in the acid hydrolysate was determined by
      Marfey's method. The structure of SPF-5506-A4 was established as Ac-Aib-L-Asn-L
      Ile-Aib-L-Pro-L-Ser-L-Ile-Aib-L-Pro-L-Leu-L-Leu-Aib-L-Pro-L-leucinol. The
      compound inhibited amyloid beta-peptide formation in primary guinea pig cerebral
      cortex neuron cell culture dose-dependently with an IC50 of 0.1 microg/ml.
      Cytotoxicity was not observed at concentrations of <3 microg/ml.

PMID- 17446691
TI  - Penisporolides A and B, two new spiral lactones from the marine-derived fungus
      Penicillium sp.
AB  - In our continued screening on bioactive constituents from marine-derived fungi,
      two novel compounds containing a rare spiral-lactone skeleton were isolated from
      lyophilized culture broth of the marine-derived fungus Penicillium sp. The
      structures of penisporolides A and B were elucidated on the basis of extensive 1D
      and 2D NMR as well as HRESI-MS spectroscopic data analysis. The relative
      stereochemistries of the compounds were assessed by analysis of NOESY data
      together with the comparison with data from previous literatures.

PMID- 17446692
TI  - Piericidins C7 and C8, new cytotoxic antibiotics produced by a marine
      Streptomyces sp.
AB  - Piericidins C7 and C8, two new members of the piericidin family, were isolated
      from a marine actinomycete. The producing organism was identified as Streptomyces
      sp. based on the cultural, biochemical and chemotaxonomical characteristics as
      well as the 16S rRNA sequence. Piericidins C7 and C8 showed selective
      cytotoxicity against rat glia cells transformed with the adenovirus E1A gene
      (IC50 C7: 1.5 nM, C8: 0.45 nM) and Neuro-2a mouse neuroblastoma cells (IC50 C7:
      0.83 nM, C8: 0.21 nM).

PMID- 17446693
TI  - Structures of new cytotoxic antibiotics, piericidins C7 and C8.
AB  - Two new cytotoxic antibiotics, piericidins C7 (1) and C8 (2), were isolated from
      a marine Streptomyces sp. High-resolution FAB-MS established the molecular
      formulae of 1 and 2 as C28H41NO5 and C29H43NO5, respectively. The planar
      structures of the piericidins were elucidated by NMR spectral analysis including
      COSY, HMQC and HMBC. The relative stereochemistry of 2 was determined based on
      NOESY and coupling constant analyses. 1 and 2 are new members of the piericidin
      family possessing 11,12-epoxide and 12-butenyl groups.

PMID- 17446694
TI  - Nigerasperones A approximately C, new monomeric and dimeric naphtho-gamma-pyrones
      from a marine alga-derived endophytic fungus Aspergillus niger EN-13.
AB  - Three new naphtho-gamma-pyrones, 5-hydroxy-6,8-dimethoxy-2-hydroxymethyl-4H
      naphtho[2,3-b]pyran-4-one (1, nigerasperone A), 3,3'-dihydro-2,2',5,5'-tetrahy
      droxy-8,8',10,10'- tetramethoxy-2,2'-dimethyl-(6',9-bi-4H-naphtho[1,2-b]pyran)
      4,4'-dione (2, nigerasperone B), and 3'-hydro-2',5,5',8-tetrahydroxy-6,6',8'
      trimethoxy-2,2'-dimethyl-(7,10'-bi-4H-naphtho[2,3-b]pyran)-4,4'-dione (3,
      nigerasperone C), together with nine related known compounds were characterized
      from Aspergillus niger EN-13, an endophytic fungus isolated from the marine brown
      alga Colpomenia sinuosa. Their structures were elucidated by detailed analysis of
      spectroscopic data and by comparison with literature reports. In the cytotoxic
      assay, these compounds did not show remarkable inhibitory effects against A549
      and SMMC-7721 tumor cell lines. However, 3 and several known compounds showed
      weak antifungal activity against Candida albicans and moderate activity on DPPH
      scavenging.

PMID- 17446695
TI  - Chemomicin A, a new angucyclinone antibiotic produced by Nocardia mediterranei
      subsp. kanglensis 1747-64.
AB  - A new angucyclinone antibiotic, chemomicin A was isolated from cultured broth of
      Nocardia mediterranei subsp. kanglensis 1747-64. Its chemical structure was
      determined to be 1,2,3,4a,5,6,6a,12a,12b-nonahydro-1,2,3,8,12,12b-hexahydroxy-3
      methyl-6a,12a-epoxybenz[a]anthracen-4,7(12H)-dione by a detailed spectroscopic
      analysis. Chemomicin A had antimicrobial activity against Bacillus subtilis and
      Enterococcus faecium with MIC values of 10.2 and 20.4 microM, respectively, and
      showed cytotoxicity against human colorectal cancer HCT116 cells and human
      esophageal carcinoma YES-2 cells with IC50 values of 127 and 153 microM,
      respectively.

PMID- 17446696
TI  - Bispolides, novel 20-membered ring macrodiolide antibiotics from microbispora.
AB  - Seven new related compounds named bispolides A1, A2, A3, B1, B2a, B2b and B3,
      have been found in a culture of Microbispora sp. A34030, isolated from a
      Malaysian soil sample. The planar structures were elucidated to be new 20
      membered ring macrodiolide antibiotics on the basis of MS and NMR spectroscopic
      analyses. These antibiotics showed a good anti-MRSA activity in vitro.

PMID- 17446697
TI  - Selective and potent in vitro antimalarial activities found in four microbial
      metabolites.
AB  - Antimalarial activities have been identified in four microbial metabolites
      through a screening programme of existing compounds in the Kitasato Institute
      chemical library. Hedamycin showed selective and potent activity against both
      drug-resistant and drug-sensitive strains of Plasmodium falciparum. Simaomicin
      alpha exhibited remarkably strong antimalarial activity, although its activity
      against a drug-resistant strain was weaker than that against a drug-sensitive
      strain. The antimalarial effects of triacsins C and D are also reported.

PMID- 17446698
TI  - Dynamics of glucocorticoid receptor and mineralocorticoid receptor: implications
      from live cell imaging studies.
AB  - Adrenal corticosteroids (cortisol in humans/corticosterone in rodents) readily
      enter the brain and exert markedly diverse effects, such as the stress response
      of target neural cells. These effects are regulated via two receptor systems, the
      mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR), both of
      which are ligand-inducible transcription factors. It is generally accepted that
      GR and MR predominantly reside in the cytoplasm in the absence of corticosterone
      (CORT), and are quickly translocated into the nucleus upon binding CORT. Then
      these receptors form dimers to bind hormone-responsive elements and regulate the
      expression of target genes. Given the different actions of MR and GR in the
      central nervous system, it is important to elucidate how the trafficking of these
      receptors between the cytoplasm and nucleus and their interaction are regulated
      by ligands or other molecules to exert transcriptional activity. However, the
      precise mechanisms of these processes are still not completely clarified. To
      address these issues, we have tried to observe more dynamic subcellular
      trafficking processes in living cells by employing a green fluorescent protein.
      In this review, we describe our recent studies of corticosteroid receptor
      dynamics in living cells focusing on three points: (1) the effects of a ligand,
      corticosteroid; (2) the carrier molecules involved in active nuclear transport,
      importins, and (3) the possibility of heterodimer formation. These studies
      demonstrate that GR and MR were quickly translocated from the cytoplasm to the
      nucleus after CORT treatment by associating with importin molecules. GR and MR
      differed in their response to the concentration of CORT in neural cells and non
      neural cells. In the nuclear region, we detected GR-MR heterodimers, which were
      affected by changes in CORT concentrations in response to various hormonal
      milieus such as circadian rhythm and stress.

PMID- 17446699
TI  - Pulmonary involvement in Behcet's disease.
AB  - BACKGROUND: Behcet's disease (BD) is a multisystem vasculitis and pulmonary
      involvement in BD is reported to indicate poor prognosis and high mortality.
      OBJECTIVES: The aims of this study were to report on patients with pulmonary
      involvement and to discuss pulmonary artery thrombus and small-sized vasculitis
      associated with BD, with respect to previously published cases. METHODS: Fifteen
      patients with BD and pulmonary involvement were included in this study. Massive
      hemoptysis was observed in all patients having pulmonary artery aneurysm (PAA).
      RESULTS: Eleven patients had macroscopic pulmonary vascular disease (2 PAA, 3 PAA
      and thrombi and 6 only thrombi) and 3 patients had microscopic pulmonary vascular
      disease. The remaining patient had pulmonary cryptococcosis. CONCLUSIONS: Data
      regarding treatment and outcomes of patients having BD-related pulmonary
      emboli/infarct and small-sized vasculitis are limited. Pulmonary vasculitis
      affects different levels of the pulmonary artery in BD and should be classified
      as macroscopic and microscopic vascular disease. 'Pulmonary artery thrombosis'
      should be used instead of 'pulmonary emboli'. Spiral CT angiography is the best
      radiological tool for evaluation of pulmonary problems in BD. Treatment of
      vasculitis should be based on the type of vascular disease and may vary among
      different types of vascular disease. Anticoagulation can be used in patients with
      microscopic vascular disease and nonaneurysmal macroscopic vascular disease. More
      studies are needed to clarify this issue.

PMID- 17446700
TI  - An observational study on the effects of nadroparin-based and citrate-based
      continuous venovenous hemofiltration on calcium metabolism.
AB  - BACKGROUND: To study calcium homeostasis during citrate-based compared to
      nadroparin-based CVVH in critically-ill patients with acute renal failure.
      METHODS: 11 patients were observed during citrate anticoagulation, 9 with
      nadroparin and 10 controls. Citrate was chosen for patients with active or at
      risk for bleeding. RESULTS: The controls had, at 24 h, a median serum iCa of 1.1
      mmol/l, the citrate group 0.87 mmol/l and the nadroparin group 1.1 mmol/l
      (citrate vs. control p = 0.001, citrate vs. nadroparin p = 0.002). At 48 h, iCa
      was not significantly different anymore. Ca balance was negative for the citrate
      group in contrast to the nadroparin group (p = 0.012). Median serum PTH was
      higher (30.0 pmol/l vs. 6.5 pmol/l, p = 0.003) in the citrate group. CONCLUSION:
      With a relative low target-serum-iCa (0.8-0.9 mmol/l) citrate CVVH-treated
      patients had a negative daily calcium balance and a temporarily lower iCa level
      resulting in an enhanced PTH response in comparison to nadroparin.

PMID- 17446701
TI  - Behavioural measures in frontotemporal lobar dementia and other dementias: the
      utility of the frontal behavioural inventory and the neuropsychiatric inventory
      in a national cohort study.
AB  - BACKGROUND: Distinguishing between patients with frontotemporal lobar dementia
      (FTLD) and other dementing illnesses remains a difficult task for many
      clinicians. In this study, we aimed to provide further evidence for the construct
      validity of the frontal behavioural inventory (FBI) and assess its utility in
      differentiating FTLD patients from other groups using data from the Canadian
      Collaborative Cohort of Related Dementias (ACCORD) study. METHOD: Baseline scores
      on the FBI and neuropsychiatric inventory (NPI) were compared among several
      clinical groups (n = 177). RESULTS: The FBI discriminated a higher percentage of
      FTLD patients (>75% correct classification) from Alzheimer's disease and other
      groups compared to the NPI (54.2%). CONCLUSION: This study provides good evidence
      for convergent validity between the FBI and NPI (r = 0.72), indicating that both
      measures capture similar psychopathology in this nationwide cohort.

PMID- 17446702
TI  - Surgical treatment of advanced gastric cancer: Japanese perspective.
AB  - The results of clinical trials regarding surgery of curable advanced gastric
      cancer and esophagogastric junction (EGJ) tumors are reviewed and summarized.
      Four clinical trials have evaluated D2 dissection for curable gastric cancer in
      the West. Two large trials in the UK and the Netherlands failed to prove the
      efficacy of D2 dissection. However, these trials had critical weak points. As
      they were carried out in a number of hospitals where there was no experience with
      this surgery, the quality of surgery and postoperative care were very poor making
      the hospital mortality unacceptably high. After these trials, an Italian group
      started a phase II study in 8 hospitals with a relatively high volume to confirm
      the safety of this procedure for Caucasians. They achieved 3% mortality, which
      was much smaller than that of even D1 in the former trials. These results first
      highlighted the importance of learning and hospital volume in D2 dissection.
      Survival results of the Dutch trial showed some difference between D1 and D2, but
      the difference was not statistically significant. This was attributed to the high
      hospital mortality and poor quality of surgery, especially low compliance of D2
      and the high rate of extension of D1, making this comparison similar to that
      between D1.3 and D1.7. The results of the phase III study by the Italian group
      are awaited. Recently a Taiwanese trial proved the benefit of D2 dissection over
      D1 in a phase III trial. This was a single institutional trial with a sample size
      of 221 patients. The 5-year survival rate of D2 and D1 was 59.5 and 53.6%,
      respectively (p = 0.04). The Dutch trials for EGJ tumors showed a large
      difference in overall survival between the transthoracic and transhiatal approach
      for Siewert type 1 and 2 tumors, but this was not statistically significant, most
      likely due to the small sample size. In the subgroup analysis, they demonstrated
      that there was no survival difference in Siewert type 2 but a large difference in
      Siewert type 1. A Japanese study showed that there is no benefit to the thoraco
      abdominal approach over the transhiatal approach for EGJ tumors whose invasion in
      the esophagus is 3 cm or less. These two trials clearly demonstrated that
      mediastinal dissection through a right thoracotomy is recommendable for Siewert
      type 1, while the transhiatal approach should be considered as standard for
      Siewert type 2.

PMID- 17446703
TI  - Surgical treatment for esophageal cancer. Current issues.
AB  - Esophageal cancer is one of the most difficult malignancies to cure. The
      prognosis remains unsatisfactory despite significant advances in surgical
      techniques and perioperative management. The optimal treatment strategy for
      localized esophageal cancer has not yet been established. Surgical resection
      remains the mainstay of treatment for esophageal cancer, and curative resection
      is the most important surgery. Extended esophagectomy with three-field
      lymphadenectomy provides the highest quality of tumor clearance and prolongation
      of patient survival. There has been intense effort in developing novel strategies
      to treat patients with resectable esophageal cancer. Various combined-modality
      approaches have been attempted to improve treatment outcomes. Definitive
      chemoradiotherapy has an impact on long-term survival in patients with resectable
      esophageal cancer. Accordingly, there are three main combined-modality
      approaches: esophagectomy with adjuvant chemotherapy or chemoradiotherapy;
      primary definitive chemoradiotherapy with or without salvage esophagectomy, and
      preoperative chemoradiotherapy followed by planned esophagectomy. Recently, owing
      to the remarkable advances in optical technology, minimally invasive
      esophagectomy using endoscopic instruments has been introduced into esophageal
      cancer surgery. This article reviews recent changes in the treatment of
      esophageal cancer surgery, and considers the role of esophagectomy.

PMID- 17446704
TI  - Surgical treatment for digestive cancer. Current issues - colon cancer.
AB  - BACKGROUND: Due to the westernization of the diet in Japan, the incidence of
      colorectal cancer has increased 4.5 times in the last 25 years. In this review,
      the recent results of surgical treatment for colonic cancer and the future
      perspectives in Japan are described. MATERIALS AND METHODS: A multi-institutional
      registry of large bowel cancer in Japan of 10,809 patients with colonic cancer
      treated from 1991 to 1994 was investigated. The data have been published in the
      Guidelines of the Japanese Society for Cancer of the Colon and Rectum (2005).
      Regarding laparoscopic surgery, 1,495 patients with colon cancer were examined in
      a multicenter study between April 1993 and August 2002. RESULTS: Radical
      resection with a curative intent is appropriate for 83-99% of the patients with
      stage I-III localized colon carcinoma. Adequate lymphadenectomy, including
      paracolic, intermediate and principal node dissection (D3 lymphadenectomy), is of
      critical importance for both the accurate staging and local control of the
      disease. This treatment protocol has now been accepted as a 'standard' operation
      by Japanese colorectal surgeons. For patients undergoing a curative resection for
      colon cancer, the 5-year survival rates vary between 62 (stage III) and 91%
      (stage I). Adjuvant chemotherapy using 5-FU/leucovorin or oral compounds is
      commonly administered to patients with stage III disease. Laparoscopic surgery
      for colonic cancer yielded a comparable oncological outcome to that reported for
      conventional open surgery in the Japanese registry for all disease stages.
      CONCLUSION: Radical resection with a D3 lymphadenectomy provided satisfactory 5
      year survival for patients with stage I-III colon cancer in Japan. However, the
      survival of patients with stage IV disease is still unsatisfactory (only a 14% 5
      year survival). Any further improvements depend on both identifying such patients
      at an earlier stage as well as developing new and effective treatment modalities.

PMID- 17446705
TI  - Current surgical management of rectal cancer.
AB  - The management of rectal cancer has undergone significant evolution over the past
      decade with improvements in both surgical technique and adjuvant therapies. The
      progression of surgical management has been of particular interest, as surgery is
      the only potentially curative treatment. The major goals of surgery are to
      optimize oncologic outcome and maintain anorectal and genitourinary function.
      There are presently two approaches to rectal cancer surgery: total mesorectal
      excision (TME), which is the gold standard in the Western world, and lateral
      lymph node dissection, which was originally developed in Japan. Although the
      results of lateral lymph node dissection are similar to TME with prior
      radiotherapy, low positive lateral lymph node yields, questionable prognostic
      significance, and high morbidity are the main drawbacks of this procedure.
      Despite the current quality of these surgical procedures, locoregional treatment
      is limited as advanced primary rectal cancer may be associated with systemic
      spread of disease. Adjuvant therapy therefore plays a key role in obtaining
      further improvement in survival. In this article, evidence for the use and
      benefits of lateral lymph node dissection surgery for rectal cancer patients in
      Japan is reviewed, and its application in association with TME and other
      modalities considered.

PMID- 17446706
TI  - Surgical treatment for liver cancer. Current issues.
AB  - Surgical treatment of hepatocellular carcinoma (HCC) has developed remarkable for
      several reasons. The surgical mortality rates of patients with HCC after
      hepatectomy have decreased due to appropriate criteria for surgery, refined
      surgical techniques and improvement in the pre- and postoperative management. In
      preoperative management, refinements in liver function tests and strategies for
      esophageal varices, and the induction of preoperative portal vein embolization
      have contributed favorably to the outcome after hepatectomy for HCC. Furthermore,
      hepatectomy has been technically refined by various vascular control methods and
      liver transection devices based on the realization that surgical anatomical
      information also plays a major role in improving surgical outcome. Also
      concomitant splenectomy with hepatectomy might extend the criteria for surgery in
      HCC patients with hypersplenism. Therefore, hepatectomy is a safe therapeutic
      approach that could bring about a favorable outcome in patients with HCC.
      Nowadays transplantation is one of the therapeutic options for HCC patients, even
      in Japan. Herein the surgical treatment of HCC in Japan is reviewed and current
      issues in the surgical treatment of HCC are discussed.

PMID- 17446707
TI  - Liver transplantation for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) has been a major reason for liver transplantation
      (LT). Globally, LT for HCC is performed on the basis of the Milan criteria, and
      if performed within those criteria, then the outcome is not different from that
      of LT performed for other primary diseases. On the other hand, the scope of the
      Milan criteria covers only early-stage HCC, and many HCC patients do not meet the
      criteria even at the time of diagnosis. Therefore, over the last decade, efforts
      have been made to perform LT for patients whose clinical characteristics lie
      outside the Milan criteria. In Japan, more than 99% of LTs are living donor LTs
      (LDLTs) and more than 15% of LTs are performed in patients with HCC. The 1- and 3
      year actual survival rates of LDLT for HCC in Japan are 82 and 79%, respectively.
      Efforts to extend the Milan criteria have also been made in Japan. To improve the
      outcome of LT for HCC, pre- and postoperative management of hepatitis B and
      hepatitis C, and immunosuppressant specific for this type of LT are still crucial
      issues. In this review, we provide an overview of current outcome, efforts to
      extend the Milan criteria, control of viral hepatitis, and immunosuppression for
      LT in patients with HCC.

PMID- 17446708
TI  - Status of surgical treatment of biliary tract cancer.
AB  - Complete surgical resection of biliary tract carcinoma remains the best
      treatment. The Japanese Society of Biliary Surgery has organized a registry
      project and established a classification of biliary tract carcinoma. We report
      here the status of biliary surgery in Japan. For hilar bile duct carcinoma, major
      hepatectomy is needed to increase the resection rate, and total caudate lobectomy
      is required for curative resection. The 5-year survival rate was 39.1%. Middle
      and distal bile duct carcinomas were treated with pancreatoduodenectomy (PD) or
      pylorus-preserving PD (PPPD) or bile duct resection alone. The 5-year survival
      rate was 44.0%. The treatment of gallbladder carcinoma with pT1 lesions is
      cholecystectomy. The treatment of pT2 lesions is extended cholecystectomy or
      various hepatectomy with or without extrahepatic bile duct resection along with
      lymphadenectomy. Treatment of pT3 and pT4 lesions includes hepatectomy with or
      without bile duct resection, combined with vascular resection, extended
      lymphadenectomy, and autonomic nerve dissection. Several groups in Japan have
      performed hepatopancreatoduodenectomy. The 5-year survival rate of pT1, pT2, pT3,
      and pT4 were 93.7, 65.1, 27.3, and 13.8%. PD or PPPD is the standard operation
      for carcinoma of the papilla of Vater. The 5-year survival rate was 57.5%.

PMID- 17446709
TI  - Vascular endothelial growth factors C and D represent novel prognostic markers in
      colorectal carcinoma using quantitative image analysis.
AB  - BACKGROUND/AIMS: Vascular endothelial growth factor C (VEGF-C) and vascular
      endothelial growth factor D (VEGF-D) are potent lymphangiogenic and angiogenetic
      mediators in many kinds of tumors. However, the exact impacts of VEGF-C and VEGF
      D on the prognosis of colorectal cancer (CRC) remain elusive. The aims of this
      study were to demonstrate the expression of VEGF-C and VEGF-D and to correlate
      their expression levels with clinicopathological factors and long-term survival
      in patients with CRC. PATIENTS AND METHODS: Between January 1996 and January
      1998, 69 patients with pathologically confirmed CRC who received routine follow
      up at the Ruijin Hospital were included in this study. VEGF-C and VEGF-D protein
      expression and microvessel density of 69 surgical specimens were assessed by
      immunohistochemistry, with 20 samples of normal colorectal tissues as controls.
      All patients were followed up for 108 months or until death. The
      Immunohistochemical stains were quantified and analyzed by means of a Zeiss
      Axioplan 2 imaging analysis system. RESULTS: The protein expression of VEGF-C and
      VEGF-D in tumor tissues was much higher than that in normal colorectal tissues (p
      < 0.01). The VEGF-C expression significantly correlated with lymph node
      metastasis (p = 0.011) and clinical stages of CRC (p < 0.01). The VEGF-D
      expression correlated with patient ages (p = 0.013), depth of tumor invasion (p =
      0.013), and lymph node metastasis (p = 0.028). The expression of VEGF-C and VEGF
      D was significantly correlated with the microvessel density. Both overall
      survival and disease-free survival at 108 months were significantly lower in the
      CRC patients with a high VEGF-C and/or a high VEGF-D expression, and the patients
      with a high expression of both VEGF-C and VEGF-D had the shortest overall
      survival and disease-free survival when compared with other patients. CONCLUSION:
      The VEGF-C or VEGF-D expression was significantly correlated with lymph node
      metastasis and long-term prognosis and could be applied as prognostic markers in
      CRC.

PMID- 17446710
TI  - Sutureless vascular anastomoses by N-butyl-2 cyanoacrylate adhesive: an
      experimental animal study.
AB  - BACKGROUND: The purpose of this animal study was to find out whether sutureless
      anastomoses using N-butyl-2-cyanoacrylate were effective in the suppression of
      neointimal hyperplasia or not. MATERIAL AND METHODS: Ten male adult mongrel dogs
      were used in this animal study. The animals were randomly divided into a control
      group (n = 5) and a study group (n = 5). The study group underwent sutureless
      anastomoses using N-buthyl-2-cyanoacrylate adhesive. Infrarenal aortoaortic graft
      was interposed using polytetrafluoroethylene. RESULTS: In the study group, the
      mean intimal thickness at the proximal anastomosis was 27.4 +/- 1.94 microm and
      27.4 +/- 1.51 microm at the distal anastomosis. In the control group, the mean
      intimal thickness was 138.4 +/- 5.02 mum at the proximal anastomosis and 67.6 +/-
      6.42 microm at the distal anastomosis. Intimal thickness at the proximal and
      distal anastomoses in the control group was significantly (p < 0.001) greater
      than in the study group. Also, perianastomotic inflammation was more obvious in
      the control group compared to the study group (p < 0.01). CONCLUSION: Sutureless
      anastomoses using with N-butyl-2-cyanoacrylate adhesive might be a good
      alternative to conventional suture technique.

PMID- 17446711
TI  - Muscle quality, aerobic fitness and fat mass predict lower-extremity physical
      function in community-dwelling older adults.
AB  - BACKGROUND: Muscle mass, strength and fitness play a role in lower-extremity
      physical function (LEPF) in older adults; however, the relationships remain
      inadequately characterized. OBJECTIVE: This study aimed to examine the
      relationships between leg mineral free lean mass (MFLM(LEG)), leg muscle quality
      (leg strength normalized for MFLM(LEG)), adiposity, aerobic fitness and LEPF in
      community-dwelling healthy elderly subjects. METHODS: Fifty-five older adults
      (69.3 +/- 5.5 years, 36 females, 19 males) were assessed for leg strength using
      an isokinetic dynamometer, body composition by dual energy X-ray absorptiometry
      and aerobic fitness via a treadmill maximal oxygen consumption test. LEPF was
      assessed using computerized dynamic posturography and stair ascent/descent, a
      timed up-and-go task and a 7-meter walk with and without an obstacle. RESULTS:
      Muscle strength, muscle quality and aerobic fitness were similarly correlated
      with static LEPF tests (r range 0.27-0.40, p < 0.05); however, the strength of
      the independent predictors was not robust with explained variance ranging from 9
      to 16%. Muscle quality was the strongest correlate of all dynamic LEPF tests (r
      range 0.54-0.65, p < 0.001). Using stepwise linear regression analysis, muscle
      quality was the strongest independent predictor of dynamic physical function
      explaining 29-42% of the variance (p < 0.001), whereas aerobic fitness or body
      fat mass explained 5-6% of the variance (p < 0.05) depending on performance
      measure. CONCLUSIONS: Muscle quality is the most important predictor, and aerobic
      fitness and fat mass are secondary predictors of LEPF in community-dwelling older
      adults. These findings support the importance of exercise, especially strength
      training, for optimal body composition, and maintenance of strength and physical
      function in older adults.

PMID- 17446712
TI  - Prevalence of low-level hepatitis B viremia in patients with HBV surface antigen
      negative hepatocellular carcinoma with and without hepatitis C virus infection in
      Japan: analysis by COBAS TaqMan real-time PCR.
AB  - OBJECTIVES: The effect of circulating low-level hepatitis B virus (HBV), defined
      as one of the states of 'occult HBV infection', on the development of
      hepatocellular carcinoma (HCC) in HBV surface antigen (HBsAg)-negative patients
      is controversial. In addition, the prevalence of occult HBV infection strongly
      depends on the sensitivity of the HBV detection method. We investigated the
      prevalence of low-level HBV in the serum of HBsAg-negative patients with HCC
      using a newly developed, sensitive method based on real-time polymerase chain
      reaction. METHODS: Serum was examined for HBV DNA in 132 patients with HBsAg
      negative HCC (95 with hepatitis C virus [HCV] infection and 37 without detectable
      hepatitis virus infection) with the COBAS TaqMan HBV test, of which the 95% hit
      rate is 35 copies/ml (6.7 IU/ml). RESULTS: Low-level HBV DNA was detected in 2 of
      95 (2.1%) patients with HCV-related HCC and 1 of 37 (2.7%) patients with non
      viral HCC. CONCLUSION: The prevalence of the detection of circulating low-level
      HBV was low in both HBsAg-negative HCC patients with HCV infection and those
      without detectable hepatitis virus, even with the use of the most sensitive
      method for the detection of HBV. Circulating low-level HBV does not appear to
      play an important role in hepatocarcinogenesis in HBsAg-negative HCC.

PMID- 17446713
TI  - Temporal relationship between renal cyst development, hypertension and cardiac
      hypertrophy in a new rat model of autosomal recessive polycystic kidney disease.
AB  - BACKGROUND/METHODS: We have examined the hypothesis that cyst formation is key in
      the pathogenesis of cardiovascular disease in a Lewis polycystic kidney (LPK)
      model of autosomal-recessive polycystic kidney disease (ARPKD), by determining
      the relationship between cyst development and indices of renal function and
      cardiovascular disease. RESULTS: In the LPK (n = 35), cysts appear at week 3 (1.1
      +/- 0.1 mm) increasing to week 24 (2.8 +/- 2 mm). Immunostaining for nephron
      specific segments indicate cysts develop predominantly from the collecting duct.
      Cyst formation preceded hypertension (160 +/- 22 vs. Lewis control 105 +/- 20 mm
      Hg systolic blood pressure (BP), n = 12) at week 6, elevated creatinine (109 +/-
      63 vs. 59 +/- 6 micromol/l, n = 16) and cardiac mass (0.7 vs. 0.4% bodyweight, n
      = 15) at week 12, and left ventricular hypertrophy (2,898 +/- 207 vs. 1,808 +/-
      192 mum, n = 14) at week 24 (all p < or = 0.05). Plasma-renin activity and
      angiotensin II were reduced in 10- to 12-week LPK (2.2 +/- 2.9 vs. Lewis 11.9 +/-
      4.9 ng/ml/h, and 25.0 +/- 19.1 vs. 94.9 +/- 64.4 pg/ml, respectively, n = 26, p <
      or = 0.05). Ganglionic blockade (hexamethonium 3.3 mg/kg) significantly reduced
      mean BP in the LPK (52 vs. Lewis 4%, n = 9, p < or = 0.05). CONCLUSION: Cyst
      formation is a key event in the genesis of hypertension while the sympathetic
      nervous system is important in the maintenance of hypertension in this model of
      ARPKD.

PMID- 17446714
TI  - Expression of SPAM1 (PH-20) in the murine kidney is not accompanied by
      hyaluronidase activity: evidence for potential roles in fluid and water
      reabsorption.
AB  - BACKGROUND: A role for Sperm Adhesion Molecule 1 (SPAM1) hyaluronidase in murine
      kidney, where Spam1 transcript levels have been reported to be higher in males,
      has not been clarified. METHODS: Spam1 RNA and protein were studied using RT-PCR,
      in situhybridization, Western blotting, immunohistochemistry and hyaluronic acid
      substrate gel electrophoresis. Urine volume and osmolality were studied in wild
      type and Spam1 null mice. RESULTS: While RT-PCR supported a tendency of higher
      RNA expression in males, no sex difference for the protein was detectable in the
      cortex, medulla, and urine. Transcripts were predominantly localized in the
      proximal tubules and glomeruli, with lower levels in the medulla. Similarly,
      Western blotting and immunohistochemistry revealed that SPAM1 is more abundant in
      the cortex. Hyaluronidase activity was absent at neutral and acidic pH:
      suggesting non-enzymatic role(s) for SPAM1. Wild-type and Spam1 null mice given
      free access to water showed significantly reduced urine volumes (p < 0.01; n =
      12) in the latter. Baseline urine osmolality was similar in both, leading to a
      significantly (p < 0.05) lower osmolar output in the nulls. After water
      deprivation (24 h), a significant (p < 0.01) increase in urine osmolality was
      seen only for wild-type mice. CONCLUSION: SPAM1 is implicated in fluid
      reabsorption and urine concentration.

PMID- 17446715
TI  - Hepatitis C in dialysed patients--what is the current optimal treatment?
AB  - Hepatitis C virus (HCV) infection is an important cause of morbidity and
      mortality in the dialysis population. The problem is more pronounced after renal
      transplantation. It seems that immunosuppressive drugs facilitate HCV replication
      and accelerate hepatic lesions. Interferon is not recommended after renal
      transplantation because of the risk of acute rejection and graft dysfunction, and
      for this reason it is important to eradicate HCV RNA before transplantation.
      Prevention is the most important treatment measure. Good clinical practice
      together with screening of blood products and organs is of outstanding
      importance. Pegylated interferon (PEG-INF) and ribavirin are currently considered
      to be optimal therapy for HCV infection. Pegylation delays clearance of
      interferon, which leads to a more potent and longer antiviral effect. The two PEG
      INF formulations (alfa-2a and alfa-2b) with different pharmacokinetic
      characteristics are currently available. Their clearance is reduced by almost 45%
      in patients with end-stage renal disease. Taken together with the high prevalence
      of adverse effects associated with the PEG-INF, an increased awareness of their
      use in dialysis patients is reasonable. There are few published studies on
      interferon and PEG-INF therapy in uremic patients. These studies confirm that the
      rate of response to different interferon formulations in dialysis is much higher
      than in the general population, but with a higher rate of adverse events.
      Ribavirin increases the response rate to treatment with PEG-INF. Great caution is
      warranted on its use in dialysis patients, whereas in patients with renal disease
      it accumulates and causes a dose-related haemolysis. Current results are
      encouraging but limited by a small number of patients and short follow-up. Multi
      centre, controlled studies with longer follow-up are needed to establish an
      optimal protocol for the treatment of chronic HCV infection in dialysis patients.

PMID- 17446716
TI  - Beneficial long-term effects of combined oral/topical antioxidant treatment with
      the carotenoids lutein and zeaxanthin on human skin: a double-blind, placebo
      controlled study.
AB  - BACKGROUND: The skin is exposed to numerous environmental assaults that can lead
      to premature aging. Of these agents, perhaps none is more ubiquitous than the
      ultraviolet (UV) wavelengths of sunlight. The primary immediate defense against
      environmental skin damage is the antioxidant capacity of the skin. However, this
      defense system can be compromised by moderate exposure to UV light. Therefore,
      bolstering the antioxidant defense system of the skin is a potentially important
      strategy for reducing environmentally induced skin damage. AIM OF THE STUDY: This
      clinical trial was designed to study the efficacy of lutein and zeaxanthin, two
      potentially important antioxidants found naturally in the skin, upon five skin
      physiology parameters (surface lipids, hydration, photoprotective activity, skin
      elasticity and skin lipid peroxidation - malondialdehyde) of human subjects.
      These xanthophyllic carotenoids were administered either orally, topically, or in
      combination (both oral and topical routes). RESULTS: The results obtained
      indicate that the combined oral and topical administration of lutein and
      zeaxanthin provides the highest degree of antioxidant protection. However, oral
      and topical administration of these antioxidants individually also provides
      significant activity in the skin. In addition, oral administration of lutein may
      provide better protection than that afforded by topical application of this
      antioxidant when measured by changes in lipid peroxidation and photoprotective
      activity in the skin following UV light irradiation.

PMID- 17446717
TI  - Intra-oral tactile sensation and aging in a community-based population.
AB  - BACKGROUND AND AIMS: Intra-oral sensory function plays an important role in
      swallowing and food intake, yet the impact of aging on oral tactile perception is
      uncertain. This study examined the effects of age, ethnicity, and gender on
      tactile perception at specific intra-oral sites in a community-based sample of
      372 Mexican-Americans (MAs) and European-Americans (EAs). METHODS: Four levels of
      air-pressure were delivered to sites on the anterior and posterior thirds of the
      tongue and on the velum. Intensity judgments for suprathreshold air puffs were
      obtained with a direct scaling procedure. Data were analyzed by mixed model
      multivariate repeated measures ANOVA. RESULTS: Mean judgments of intensity,
      slopes of intensity functions and intraclass correlation coefficients (ICCs) for
      intensity judgments, indicated that stimuli delivered to the anterior tongue
      elicited significantly larger and more consistent responding than at the other
      sites. MAs produced lower mean stimulus intensity judgments for all sites
      compared to EAs. No significant age-, gender- or ethnic group-related differences
      were found at any of the sites for the slopes of the intensity functions or for
      ICCs. CONCLUSIONS: Stimuli are judged more intense at the anterior tongue
      compared to the posterior tongue or velum and EAs gave higher estimates of
      intensity than did MAs. However, there are no age-, gender-, or ethnic group
      related differences for the repeatability of intensity judgments or the slopes of
      intensity functions. Intra-oral tactile perception seems to be preserved during
      aging.

PMID- 17446718
TI  - Amino-bisphosphonates decrease hTERT gene expression in breast cancer in vitro.
AB  - BACKGROUND AND AIMS: Human telomerase reverse transcriptase (hTERT) is the
      catalytic subunit of telomerase. hTERT expression and telomerase activity are
      elevated in most human tumors. Bisphosphonates play an important role in the
      management of tumors with the secondary involvement of bone. METHODS: We
      investigated the effect on hTERT gene expression of clodronate, alendronate, and
      pamidronate (from 10(-6) M to 10(-5) M) on MCF-7 and T47D human breast cancer
      cells, using real time RTPCR. RESULTS: At 10(-5) M, amino-bisphosphonates
      (alendronate and pamidronate) inhibited breast cancer cell viability and induced
      a significant decrease in hTERT gene expression with respect to controls (82% and
      71% in MCF-7 cells; 74% and 60% in T47D, p<0.0001). No effect was observed with
      clodronate. CONCLUSIONS: Amino-bisphosphonates down-regulate hTERT gene
      expression. The role of hTERT is a new finding, which gives an alternative
      explanation for the direct effect of bisphosphonates on tumor cells.

PMID- 17446719
TI  - Characteristics associated with falls in patients with dementia in a
      psychogeriatric ward.
AB  - BACKGROUND AND AIMS: Few studies have reported fall-risk factors for persons with
      dementia, and no successful randomized fall prevention studies have been
      published. The aim of this study was to identify characteristics associated with
      falls in patients with dementia in a psychogeriatric ward. METHODS: This
      prospective study comprised 204 patients with any diagnosis of dementia. It was
      carried out in a psychogeriatric ward specializing in the assessment and
      treatment of behavioral and psychological symptoms in patients with dementia
      (BPSD). Baseline patient data were collected from medical records, and covered
      physical, behavioral and cognitive areas. Falls were recorded during time spent
      in the ward and median follow-up time was 52.5 days. RESULTS: Eighty-two patients
      fell a total of 251 times. Factors significantly and independently associated
      with an increased risk of falling were male sex (IRR 3.36, 95% CI 2.02-5.61),
      failed "copy design" activity (decreased visual perception) (IRR 2.37, 95% CI
      1.24-4.52), and any walking difficulty on level ground (IRR 1.84, 95% CI 1.10
      3.08). Statins were associated with a decreased risk of falling (IRR 0.29, 95% CI
      0.10-0.86). Twenty-seven percent of the variation in falls was explained.
      CONCLUSIONS: Male sex, decreased visual perception, and walking difficulties were
      all associated with an increased number of falls, and the model explained 1/4 of
      the variation in falls. Well-planned furnishing and use of color to achieve a
      plain, clearly defined environment, as well as training in walking ability, may
      decrease the risk of falling in people with dementia.

PMID- 17446720
TI  - Role of functional performance in diagnosis of dementia in elderly people with
      low educational level living in Southern Italy.
AB  - BACKGROUND AND AIMS: Diagnosis of dementia is often difficult in subjects with
      low educational level. Our aim was to evaluate the role of functional performance
      and the possibility of preferring scores of activities of daily living (ADL) and
      instrumental activities of daily living (IADL) in screening elderly people for
      diagnosis of dementia in a rural population of Southern Italy with a very high
      percentage of non-educated subjects. METHODS: a random sample of 300 residents,
      out of 1089 subjects over 60 years of age living in San Marcellino (Caserta,
      Campania), received door-to-door visit for information about their medical
      history, with clinical evaluation of general geriatric conditions, including the
      cumulative illness rating scale (CIRS). Dementia was diagnosed if subjects had a
      Clinical Dementia Rating score (CDR) > or = 1 and according to the criteria of
      DSMIV, but not according to scores on the Mini Mental State Examination (MMSE),
      ADL and IADL. Two hundred and nineteen normal subjects (NS) and 75 patients with
      dementia (DP) were evaluated. RESULTS: in NS, their mean age- and education
      corrected MMSE score was 22.15 (lower than the normal cut-off value of 23.8) and
      12.60 in DP (p<0.0001). In NS, the mean ADL score was higher than in DP (5.53 vs
      2.64, p<0.0001); only age was correlated with ADL scores (coeff=-0.44, t=-4.557,
      p<0.0001). Assuming age as covariate, ADL scores highly differentiated DP from NS
      (F(1, 289)=26.083, p<0.0001). In both sexes, mean IADL scores were higher in NS
      than in DP (4.46 vs 1.80 in men, p<0.0001; 6.85 vs 2.31 in women, p<0.0001). Age
      and education did not influence IADL scores in men, but age greatly affected
      performance in women. IADL scores clearly differentiated NS from DP. In NS, a
      positive correlation was evident between ADL and IADL scores (r=0.234, p<0.0005),
      but neither scores correlated with the MMSE scores, even when correlation was
      performed separately for men and women. In DP, a strong correlation was observed
      between ADL and IADL scores (r=0.709, p<0.0001) and significant correlations were
      also evident between the scores of MMSE and both ADL (r=0.492,p<0.0001) and IADL
      (r=0.398, p<0.0004). CONCLUSIONS: in a rural community with a high prevalence of
      non-educated subjects, cognitive impairment is related to education, whereas
      independent functioning is limited mainly to age and not to cognition, if the
      latter remains (relatively) unimpaired. These results point to the importance of
      an "ecological" approach to the evaluation of elderly people, particularly those
      living in small rural communities, where education and the social environment may
      give rise to difficulties in diagnosis of dementia. The assessment of functional
      autonomy by ADL and IADL scales may be a better screening tool in diagnosing
      dementia than the MMSE scores.

PMID- 17446721
TI  - Research partnership with underserved African-American communities to improve the
      health of older persons with disability: a pilot qualitative study.
AB  - BACKGROUND AND AIMS: Underserved ethnic minorities are often under-represented in
      clinical investigations, often in the context of poor relationships between
      academic institutions and their minority communities. The aim of this study was
      to investigate an African-American community's perceptions about the barriers
      that hinder participation in research studies and, more broadly, on the status of
      institution/community relationships. METHODS: We conducted a pilot qualitative
      study, based on semi- structured interviews of leaders of African-American
      communities in Winston-Salem, North Carolina. Relevant themes were abstracted
      from the interviews by a standardized iterative process. RESULTS: Interviewees
      identified barriers to participation of African- Americans in research, and
      suggested that existing barriers may be overcome with an innovative model of a
      community/institution relationship, which would include open communication and
      cooperation, mutually beneficial programs, holistic approaches to health and
      disease, participatory and balanced partnerships with communities, and the
      establishment of multiethnic advisory boards. CONCLUSIONS: This study suggests
      strategies that public health researchers should consider to establish effective
      institution/community relationships, in order to enhance participation of
      underserved ethnic minorities in research studies, and to improve the health
      status of their most disabled and demanding seniors.

PMID- 17446722
TI  - Does cognitive performance affect physical therapy regimen after hip fracture
      surgery?
AB  - BACKGROUND AND AIMS: To evaluate whether and which clinical factors affect the
      regimen of physical therapy (PT) treatment in elderly patients after hip fracture
      (HF). METHODS: HF patients consecutively admitted to a rehabilitation unit (from
      January 2002 to May 2004) without adverse clinical events on admission or during
      hospital stay were considered (n=80). All patients underwent multidimensional
      assessment including demographic, clinical, cognitive, affective and functional
      status. Outcome measure was the number of rehabilitative procedures (NRP),
      computed as the ratio between sum of rehabilitative procedures and length of
      hospital stay. RESULTS: Patients received 3.8+/-1.3 NRP on average, although with
      large variability. Age and impairment of cognitive and pre-fracture functional
      status were significantly higher in those receiving fewer NRP. In a multiple
      regression model, only the Mini Mental State Examination (MMSE) significantly
      predicted NRP: compared with patients with MMSE < or =17, those with MMSE = 18
      23, 24-26 and > or =27 received 0.3 (95% CI - 0.5-1.1, p=0.46), 1.5 (95% CI 0.6
      2.4, p=0.001), and 1.6 (95% CI 0.7-2.5, p=0.001) more NRP. CONCLUSIONS: Cognitive
      performance affects NRP in elderly HF patients. Specific rehabilitative
      approaches, according to baseline cognitive performance, should be considered.

PMID- 17446723
TI  - Health-related quality of life of patients with hip fracture before and after
      rehabilitation therapy: discrepancies between physicians' findings and patients'
      ratings.
AB  - BACKGROUND AND AIMS: Health-related quality of life (HrQoL) is broadly accepted
      as an evaluation criterion of medical therapy effects. The major objectives of
      this work are a) measuring of the effects of rehabilitation therapy on the HrQoL
      of elderly patients after hip fracture, and b) study of discrepancies between the
      physician's findings on one hand and subjective ratings of patients on the other,
      and their influence on HrQoL, depression, and independence in activities of daily
      living. METHODS: The study sample consisted of 95 patients surgically treated
      after a fall-induced hip fracture (mean age=82 years; range=61-97). Using the
      median as splitting criterion, ratings of patients and physicians concerning
      disturbance-specific functional capacity were subdivided into positive and
      negative. This led to separation of the sample into four subgroups: the fortunate
      (congruent positive ratings), satisfaction paradox (positive subjective, negative
      objective ratings), dissatisfaction dilemma (negative subjective, objective
      positive ratings), and the unfortunate (congruent negative ratings). RESULTS: The
      four patient subgroups diverged in their estimations. The subgroups of the
      fortunate and satisfaction paradox have had the highest subjective gains in
      HrQoL. The subgroups of dissatisfaction dilemma and the unfortunate estimated
      their gains as similarly low on most of the tested scales. CONCLUSIONS: Results
      stress the importance of subjective factors in processes concerning therapy
      evaluations and their influence on HrQoL. The objective success of therapy is not
      of primary importance for the extent of the HrQoL, but subjective evaluation of
      it is.

PMID- 17446724
TI  - Residential facilities for older people in Italy: a five-region survey.
AB  - BACKGROUND AND AIMS: To survey all Residential Facilities (RFs) for older people
      (more than 50% residents over 65 years of age) in five Italian regions (Calabria,
      Sardinia, Sicily, Umbria, Veneto), and to evaluate their logistic and
      organizational characteristics and staff and resident features. METHODS:
      Structured interviews with RF managers; selected RFs operating in five regions.
      RESULTS: A total of 853 RFs were operating in the five regions, with an average
      of 198.0 beds per 10,000 older people - a rate showing marked regional
      variability. The number of RFs actually surveyed was 754 (88.4% of sample pool).
      The mean number of RF beds was 59.8 (+/-65.0; median: 34), and the great majority
      (96%) had 24-hour staff cover. A large proportion (29%) were managed by local
      municipal authorities, religious non-profit associations (approx. 24%) and other
      non-profit organizations (approx. 21%). In the RFs 24,456 workers were employed;
      the number of staff per facility also showed great variability. The mean number
      of workers directly involved in resident care was 27.8 (+/-39.0; range: 1-331);
      the median number of staff members was 14, and the resident/staff ratio was 2.1.
      These 754 RFs hosted 42,687 residents, with an average of 53.5 (+/-58.5) older
      people in each facility, and 3.2 residents below the age of 65. The mean age of
      the entire resident sample was 79.3 years (+/-5.2) and there was a high
      proportion of residents with neurological (including dementia), psychiatric and
      medical disorders. CONCLUSIONS: The five regions varied considerably in
      residential bed provision; many other RF characteristics, including
      staff/resident ratios, showed similar variability. Most RFs hosted older people
      with a variety of neurological, psychiatric and medical disorders. Future phases
      of the project will aim at shedding light on many other features in these
      institutions, which care for 2.1% of the older population in Italy and may serve
      even greater proportions of older people in the future.

PMID- 17446725
TI  - Effect of cognitive impairment on basic activities of daily living in hip
      fracture patients: a 1-year follow-up.
AB  - BACKGROUND AND AIMS: To compare changes in basic self-care activities in various
      cognitive groups of hip fracture patients by the Katz Index of Independence in
      activities of daily living (ADL). METHODS: 117 community-dwelling elderly
      subjects with acute hip fracture (age 67-92 years), referred to the geriatric
      unit of Jyvaskyla Central Hospital for rehabilitation, participated in the study.
      Basic self-care activities were evaluated by the Katz ADL Index and cognition by
      the Mini-Mental State Examination (MMSE). RESULTS: Prior to hip fracture, the
      patients in the lowest MMSE group had a significantly lower Katz Index than the
      other three groups (p<0.001). Disability increased in a statistically
      significantly way post-surgery in all four MMSE groups (p<0.001). In the two
      lower MMSE groups, the Katz Index remained at the lower level, and in the two
      higher groups it improved in a statistically significant way from 2 weeks to 3
      months post-operatively, after which it deteriorated slightly. A significantly
      larger proportion of patients in the higher MMSE groups were independent in all
      basic ADLs, both before and after fracture (from p=0.023 to p<0.001), except in
      continence prior to fracture. CONCLUSIONS: Prior to hip fracture, patients with
      low MMSE scores had a significantly greater degree of basic ADL dependence than
      the other three groups. Despite similar post-operative multidisciplinary
      treatment, functional ability remained at the lower level in the two lower MMSE
      groups, whereas recovery was much better in the higher MMSE groups.

PMID- 17446726
TI  - Frailty and survival of rural and urban seniors: results from the Canadian Study
      of Health and Aging.
AB  - BACKGROUND AND AIMS: Relatively little is known about how region of residence
      influences frailty of seniors. Frailty indexes can be used to investigate these
      effects. We constructed and validated a frailty index, to investigate the
      differences in health status between rural and urban seniors. METHODS: We studied
      rural (n=949) and urban (n=7598) older adults in the Canadian Study of Health and
      Aging, of whom 22% died over 72 months. The frailty index was generated from 40
      self-reported health deficits (symptoms, diseases, disabilities, unfavourable
      living conditions). RESULTS: The average value of the frailty index increased
      exponentially with age in both groups (rural: r=0.94; urban: r=0.97, p<0.01) and
      was highly correlated with mortality (r=0.96 for rural, r=0.97 for urban,
      p<0.01). Up to age 80, there were few rural-urban differences in frailty. After
      age 80, the rural sample showed higher mortality than the urban sample. The
      hazard ratio for death for each increment in the frailty index was 1.38 (1.14
      1.72) in rural participants vs 1.18 (1.11-1.26) in urban participants. Women
      lived longer than men at any index value. CONCLUSIONS: Frailty index analysis
      readily summarizes health and mortality differences between very old rural and
      urban dwellers, which reflect differences in deficit accumulation, and in the
      impact of gender on survival. The frailty index provides efficient dimensionality
      reduction for studying group differences in the health of older adults.

PMID- 17446727
TI  - High baseline values of fat mass, independently of appendicular skeletal mass,
      predict 2-year onset of disability in elderly subjects at the high end of the
      functional spectrum.
AB  - BACKGROUND AND AIMS: To evaluate the relation between baseline body composition
      and 2- year onset of functional limitation in elderly subjects at the high end of
      the functional spectrum. METHODS: Anthropometric measurements, physical
      functioning as measured by a modified version of the Activities of Daily Living
      Scale, and baseline albumin, were evaluated in 145 men and women aged 66-78
      years, free of functional limitations, selected from the general population of
      Verona. In each subject, total body fat mass (FM) and appendicular FFM (ASMM)
      were measured by dual-energy X-ray absorptiometry; the FM (FMI) and ASMM indexes
      (ASMMI) were also calculated by dividing each body composition variable by height
      squared. RESULTS: After 2 years of follow-up, 48.2% of women and 40% of men had
      developed mild levels of disability, with limitations in kneeling, bending and
      climbing stairs. In women, but not in men, a BMI higher than 25 Kg/m2 or values
      of FMI higher than the 50th percentile, were significantly associated with a 3 to
      5 times increased risk of limitations in climbing stairs and lower body
      performance. In men, a trend was found between low values of ASMMI and an
      increased risk of limitations in kneeling and bending. After cross-tabulating
      categories based on the 50th percentile of ASMMI and FMI, high values of FMI,
      independently of ASMMI, were significantly related with higher incidence of
      limitation in climbing stairs in women. In women, the highest 2-year incidence of
      limitation in climbing stairs was found in the group of obese subjects.
      CONCLUSIONS: High body fat and high BMI values were associated with a greater
      probability of developing functional limitations 2 years later in a population of
      elderly subjects at the high end of the functional spectrum. Moreover, in women,
      high baseline values of fat mass, independently of appendicular fat-free mass,
      were more likely to predict the future onset of functional limitations.

PMID- 17446728
TI  - New approach to gerontology: building up "successful aging" conditions.
AB  - BACKGROUND AND AIMS: Great efforts have been made in developed societies to
      extend human life expectancy as much as possible. Continuing investments into
      extending the life-span into the "fourth age" actually reduce the opportunities
      of people to age successfully and die in dignity. Consequently, in recent years,
      the concept of "Successful Aging" (SA) has gained increased attention:
      investigators recognize the importance of separating pathologic changes from
      those which may be attributed to aging in itself, in order to interpret correctly
      the differences between Pathologic Aging, Normal Aging, and Successful Aging.
      Hence, according to recent literature on aging, our aim was to question here the
      validity of recommendations made in the literature for policy making in the
      treatment of aging and suggest new alternatives. METHODS: We have tried to
      understand and develop a method of analysis to the following question: what do we
      actually mean by SA? Successful Aging may be seen as an arbitrary, subjective
      term, so we studied which indicators characterize elderly persons as successful
      aged. RESULTS: The results of this study show that older people's views of SA
      appear to be multidimensional and more complex than the apparent viewpoint of
      many of early studies, which tended to focus on a single dimension of health -
      psychological or mental. CONCLUSIONS: We argue the proper use of various health
      indicators and health enhancers, as proposed in the current international
      literature, in the definition of SA.

PMID- 17446729
TI  - Estrogen Receptor 1 gene (ESR1) variants in Alzheimer's disease. Results of a
      meta-analysis.
AB  - BACKGROUND AND AIMS: There is some disagreement between clinical and basic
      science as to the benefit of estrogen in preventing cognitive decline. For
      cardiovascular disease, estrogen effects have been shown to vary with estrogen
      receptor (ESR) genotype. The present study was conceived to review evidence of
      ESR association with Alzheimer's disease (AD) which could account for the
      variability observed in estrogen treatment outcome. METHODS: A meta-analysis was
      performed on data from 8288 cases and controls, controlling for ethnicity (Asian
      vs European). To explore the specificity of our findings further, a second meta
      analysis of association studies was then appended, addressing non-AD forms of
      dementia or cognitive impairment (total n=11036). RESULTS: A significant overall
      association of AD with two neighboring ESR1 variants located in a transcription
      enhancing region (p=0.015) was noted. The genotypic effect was driven by the
      minor alleles in Asian populations, and did not reach significance in European
      samples (OR=1.1, p>0.267). When the phenotype was extended to other forms of
      dementia or cognitive impairment, the association was no longer observed.
      CONCLUSIONS: ESR1 variability was confirmed to modulate susceptibility to AD in
      Asian individuals, but not in Europeans. More research is required to address
      possible clinical implications, e.g., for hormone replacement therapy in early
      stages of AD.

PMID- 17446731
TI  - Decision making with biomarkers after cardiac arrest: are we there yet?

PMID- 17446732
TI  - The case of rapid response systems: are randomized clinical trials the right
      methodology to evaluate systems of care?

PMID- 17446733
TI  - Is severe sepsis increasing in incidence AND severity?

PMID- 17446734
TI  - Translational highway: it helps to have a map.

PMID- 17446735
TI  - Acid-base balance analysis: a little off target.

PMID- 17446736
TI  - A legally sanctioned process for resolving conflicts about treatment considered
      medically inappropriate.

PMID- 17446737
TI  - Brain natriuretic peptides in sepsis: ideal biomarker or just along for the ride?

PMID- 17446738
TI  - Surviving sepsis outside the intensive care unit.

PMID- 17446739
TI  - Polymorphism studies in critical illness--we have to raise the bar.

PMID- 17446740
TI  - Catheters, infection, and videotapes.

PMID- 17446741
TI  - The times are a-changin': should we bury the yellow catheter?

PMID- 17446742
TI  - Safety culture: easy to advocate, difficult to create.

PMID- 17446743
TI  - Antibiotic therapy and immunosuppression: choosing an edge on a familiar double
      edged sword.

PMID- 17446744
TI  - N-Acetylcysteine for the prevention of renal dysfunction in high-risk patients
      undergoing coronary bypass graft surgery: an unfulfilled promise?

PMID- 17446745
TI  - Just the right amount of JNK: How nuclear factor-kappaB and downstream mediators
      prevent burn-induced intestinal injury.

PMID- 17446746
TI  - Fluid therapy continues to be validated in early sepsis: impact on myocardial
      depression.

PMID- 17446747
TI  - Research in resuscitation from cardiac arrest: where should we go from here?

PMID- 17446748
TI  - New therapeutic approaches for influenza A H5N1 infected humans.

PMID- 17446749
TI  - Recovery of transplantable organs after cardiac or circulatory death: the end
      justifying the means.

PMID- 17446751
TI  - A central venous pressure goal of 8-12 mm Hg for all patients in septic shock.

PMID- 17446753
TI  - Mannose binding lectin (MBL)-2 codon 54BB genotype associated with acute
      respiratory distress syndrome only by its association with bacterial infection.

PMID- 17446754
TI  - Immune modulation by parenteral lipids: platelet activating factor is not the
      only clue.

PMID- 17446756
TI  - Intravenous injection of methylprednisolone reduces the incidence of
      postextubation stridor in intensive care unit patients.

PMID- 17446759
TI  - Subcutaneous continuous glucose monitoring in severe burn patients.

PMID- 17446761
TI  - Erythromycin as a prokinetic: is the overall benefit corroborated?

PMID- 17446762
TI  - Gas exchange of lung-protective ventilation strategies in pigs with normal lungs.

PMID- 17446763
TI  - Targeting lung coagulation disorders in acute lung injury: easy as pie (PAI-1)?

PMID- 17446767
TI  - Minimizing the risk of developing cerebral edema during therapy for diabetic
      ketoacidosis.

PMID- 17446770
TI  - History of emergency and critical care ultrasound: the evolution of a new imaging
      paradigm.
AB  - The tradition of clinical ultrasound in the hands of physicians who provide
      critical care to the most acutely ill patients stretches back into the 1980s and
      is rich with experiences from surgical, emergency medicine, and other practices.
      Now, as critical care ultrasound explodes around the world, it is important to
      realize the path its development has taken and learn from trials and tribulations
      of early practitioners in the field. The development and battles for the right to
      use ultrasound at the patient's bedside for >20 yrs is described in relation to
      its emergency medicine and surgical origins. Approaches to education, scanning,
      documentation, and organization at the national and regional levels are
      described.

PMID- 17446771
TI  - Basic physics of ultrasound imaging.
AB  - The appearance of ultrasound images depends critically on the physical
      interactions of sound with the tissues in the body. The basic principles of
      ultrasound imaging and the physical reasons for many common artifacts are
      described.

PMID- 17446772
TI  - Focused ultrasound training for clinicians.
AB  - Clinician use of diagnostic ultrasound, particularly at point of care and in
      emergency situations, is well established. The standard of training courses and
      of postcourse supervision and accreditation is variable, and international
      standards are required to maintain safety, accuracy, and credibility of the
      technique. The accuracy of the technique by trained personnel has been well
      documented. There is evidence that prereading, a course involving theoretical and
      practical training, and ongoing mentoring (proctoring) provides high standards of
      practice. Regular accreditation and continuous comparison with gold standards is
      required to maintain this level. Most areas of the body are now accessible to
      clinicians of varied specialties, even those previously thought impossible for
      ultrasound examination, such as the chest and bone. Training and supervision in
      rural, remote, and austere environments provides added challenges.

PMID- 17446773
TI  - Specific skill set and goals of focused echocardiography for critical care
      clinicians.
AB  - Echocardiography in the critical care setting can provide crucial information
      about the patient's cardiac anatomy, ejection fraction, valvular function, and
      volume status. There is a need for more involvement by intensivists in performing
      focused echocardiographic studies as this modality has been well shown to improve
      patient care. Several factors limit the widespread use of this technology by
      intensivists that are noncardiologists. One of them is the lack of formal
      didactic and practical training programs in "goal-directed" echocardiography
      specifically oriented for the critical care specialist. Although it is clear that
      extensive training and experience are needed to perform and interpret a complete
      echocardiographic study, a growing body of literature demonstrates that
      noncardiology medical professionals can be trained to acquire and interpret
      echocardiographic imaging in a goal-directed or "focused" manner with an
      acceptable overall level of accuracy. Performance of such focused
      echocardiography by intensivists has been shown to provide new information not
      assessable by physical examination, and often leads to change in therapeutic
      management at the bedside. Echocardiography using the transthoracic approach is a
      noninvasive imaging modality and is of great value in the critical care setting
      because of its portability, widespread availability, and rapid diagnostic
      capability. Programs for intensivists should cover both the transthoracic and
      transesophageal approach. Focused training with the transthoracic approach should
      be offered to all intensivists, while training with the transesophageal approach
      should be offered to intensivists who desire more advanced training. This article
      will go over important issues regarding current and potential avenues for
      training of critical care physicians in performance of focused bedside
      echocardiography.

PMID- 17446774
TI  - Focused echocardiographic evaluation in resuscitation management: concept of an
      advanced life support-conformed algorithm.
AB  - Emergency ultrasound is suggested to be an important tool in critical care
      medicine. Time-dependent scenarios occur during preresuscitation care, during
      cardiopulmonary resuscitation, and in postresuscitation care. Suspected
      myocardial insufficiency due to acute global, left, or right heart failure,
      pericardial tamponade, and hypovolemia should be identified. These diagnoses
      cannot be made with standard physical examination or the electrocardiogram.
      Furthermore, the differential diagnosis of pulseless electrical activity is best
      elucidated with echocardiography. Therefore, we developed an algorithm of focused
      echocardiographic evaluation in resuscitation management, a structured process of
      an advanced life support-conformed transthoracic echocardiography protocol to be
      applied to point-of-care diagnosis. The new 2005 American Heart
      Association/European Resuscitation Council/International Liaison Committee on
      Resuscitation guidelines recommended high-quality cardiopulmonary resuscitation
      with minimal interruptions to reduce the no-flow intervals. However, they also
      recommended identification and treatment of reversible causes or complicating
      factors. Therefore, clinicians must be trained to use echocardiography within the
      brief interruptions of advanced life support, taking into account practical and
      theoretical considerations. Focused echocardiographic evaluation in resuscitation
      management was evaluated by emergency physicians with respect to incorporation
      into the cardiopulmonary resuscitation process, performance, and physicians'
      ability to recognize characteristic pathology. The aim of the focused
      echocardiographic evaluation in resuscitation management examination is to
      improve the outcomes of cardiopulmonary resuscitation.

PMID- 17446775
TI  - Clinician-performed focused sonography for the resuscitation of trauma.
AB  - Traumatic death remains pandemic. The majority of preventable deaths occur early
      and are due to injuries or physiologic derangements in the airway,
      thoracoabdominal cavities, or brain. Ultrasound is a noninvasive and portable
      imaging modality that spans a spectrum between the physical examination and
      diagnostic imaging. It allows trained examiners to immediately confirm important
      syndromes and answer clinical questions. Newer technologies greatly increase the
      fidelity, accessibility, ease of use, and informatic manipulation of the results.
      The early bedside use of focused ultrasound as the initial imaging modality used
      to detect hemoperitoneum and hemopericardium in the resuscitation of the injured
      patient has become an accepted standard of care. Widespread dissemination of
      basic ultrasound skills and technology to facilitate this brings ultrasound to
      many resuscitative and critical care areas. Although not as widely appreciated,
      the focused use of ultrasound may also have a role in detecting hemothoraces and
      pneumothoraces, guiding airway management, and detecting increased intracranial
      pressure. Intensivists generally utilize a treating philosophy that requires the
      real-time integration of many divergent sources of information regarding their
      patients' anatomy and physiology. They are therefore positioned to take advantage
      of focused resuscitative ultrasound, which offers immediate diagnostic
      information in the early care of the critically injured.

PMID- 17446776
TI  - Role of ultrasound in the airway management of critically ill patients.
AB  - Ultrasound imaging of the upper airway in critically ill patients offers a number
      of attractive advantages compared with competitive imaging techniques or
      endoscopy. It is widely available, portable, repeatable, relatively inexpensive,
      pain-free, and safe. In this review article, I describe ultrasonographic anatomy
      of the upper respiratory organs and present the main potential applications of
      ultrasonography in airway management. The role of ultrasound in endotracheal tube
      placement, including preintubation assessment, verification of tube position,
      double-lumen intubation, and extubation outcome, are explained. Also, ultrasound
      guided percutaneous tracheostomy, the role of ultrasound in using the laryngeal
      mask airway, and upper airway anesthesia are described.

PMID- 17446777
TI  - Ultrasound imaging in vascular access.
AB  - Physicians spend a considerable amount of time and effort inserting catheters and
      needles into patients. Central venous catheters are the mainstay of measuring
      hemodynamic variables that cannot be assessed by noninvasive procedures. These
      catheters also allow hemodialysis, parenteral nutritional support, delivery of
      medications, and catecholamine administration. Arterial pressure catheters are
      frequently used for hemodynamic monitoring and for obtaining arterial blood gases
      in critically ill patients. Such use of arterial and central venous catheters,
      however, is potentially associated with severe complications that can be
      injurious to patients and expensive to treat. Techniques involving the use of
      anatomic landmarks have been the traditional mainstay of accessing the central
      venous system for decades. With the development and refinement of portable and
      affordable high-resolution ultrasound devices, imaging vascular access has
      changed the role of the traditional landmark techniques. In this article, we
      explain the use of ultrasound for vascular access to reduce complications
      associated with cannulation of veins and arteries. We will also provide a brief
      overview of the current literature regarding ultrasound-guided vascular access.

PMID- 17446778
TI  - Ultrasound-guided interventional radiology in critical care.
AB  - Ultrasound-guided intervention is becoming an increasingly popular and valuable
      tool in the critical care setting. In general, image-guided procedures can
      expedite wait times and increase the accuracy, safety, and efficacy of many
      procedures commonly performed within intensive care units. In the intensive care
      unit setting, ultrasound has particular advantages over other imaging modalities
      such as computed tomography and fluoroscopy, including real-time visualization,
      portability permitting bedside procedures, and reduced exposure to nephrotoxic
      contrast agents. We review the technical and procedural aspects of a number of
      ultrasound-guided interventions appropriate for critical care patients. These
      include central venous catheter deployment, thoracentesis, paracentesis, and
      drainage of a wide variety of abscesses, and percutaneous nephrostomy,
      percutaneous cholecystectomy, and inferior vena cava filter placement. Although
      we believe ultrasound is significantly underutilized in critical care today, we
      anticipate that with the improvement of ultrasound technology and the innovation
      of new ultrasound-guided procedures, the role of ultrasound in the intensive care
      unit will continue to expand, with bedside ultrasound-guided interventions
      increasingly becoming the norm.

PMID- 17446779
TI  - Renal ultrasonography in critically ill patients.
AB  - Acute renal failure is a sudden and sustained decrease in the glomerular
      filtration rate associated with a loss of excretory function and the accumulation
      of metabolic waste products and water. It leads to an increase in serum urea and
      creatinine, usually with a decrease in urine output. Although routine
      surveillance of patients by means of laboratory examinations has been well
      defined, very little is known about renal imaging. Modern technology has provided
      a large number of sophisticated monitoring systems. Ultrasonography with color
      Doppler study of the kidneys may be indicated as a possible monitor of renal
      perfusion. Ultrasonography is often used as the initial imaging procedure in the
      examination of patients with renal failure. Aside from excluding hydronephrosis,
      it is well recognized in characterizing the type of renal disease, especially in
      an acute setting. This article describes the use of ultrasound to achieve the
      proper diagnosis of acute renal diseases and to enable the appropriate and early
      assessment of these patients in intensive care units.

PMID- 17446780
TI  - "The higher the abdominal pressure, the less the secretion of urine": another
      target disease for renal ultrasonography?

PMID- 17446781
TI  - Upper abdominal ultrasound in the critically ill.
AB  - Intraabdominal pathology, either primary or secondary, may frequently be found in
      critically ill patients. Without early diagnosis and treatment, the patient's
      condition may deteriorate and even progress to death. In this article, we provide
      a current review of the literature regarding liver, biliary, pancreatic, and
      splenic problems in critically ill patients and describe common ultrasound
      findings, including the appearance of free intraperitoneal air. According to the
      liver surface, edge, echotexture, and echogenicity, either diffuse liver diseases
      or focal liver diseases can be detected on ultrasound. By scanning the biliary
      tree and gallbladder, many right upper quadrant diseases can be diagnosed. The
      role of ultrasound for acute pancreatic pathology is to identify any lesions and
      to evaluate the severity of the diseases. Similarly, the spleen can be evaluated
      for relevant pathology in the critical care setting.

PMID- 17446782
TI  - Role of transcranial Doppler in neurocritical care.
AB  - Transcranial Doppler has several practical applications in neurocritical care. It
      has its main application in the diagnosis and monitoring of vasospasm in patients
      with subarachnoid hemorrhage. In addition, it holds promise for the detection of
      critical elevations of intracranial pressure. Its ability to measure CO2
      reactivity and autoregulation may ultimately allow intensivists to optimize
      cerebral perfusion pressure and ventilatory therapy for the individual patient.
      Transcranial Doppler findings of brain death are well described and can be useful
      as a screening tool.

PMID- 17446783
TI  - Ultrasound in the detection of venous thromboembolism.
AB  - Venous thrombosis is a common disease process leading to tens of thousands of
      deaths per year. Despite prophylactic efforts, venous thromboembolic disease is a
      common and serious complication in critical care patients. Difficulty and delay
      in obtaining diagnostic imaging studies to rule out deep venous thrombosis is
      exacerbated by increased susceptibility that critically ill patients have to
      thromboembolism. Lower extremity venous ultrasound use by clinicians has been
      well studied and has proven both reliable and efficient. Evaluation of the upper
      extremities can be more challenging and requires a higher degree of technical
      skill. However, both can be integrated into an overall scheme of prevention,
      screening, and rapid diagnosis of thromboembolic disease and its complications.
      This article delves into available literature and describes performance of both
      applications in a critical care setting.

PMID- 17446784
TI  - Bedside echocardiography in the assessment of the critically ill.
AB  - Advances in ultrasound technology continue to enhance its diagnostic applications
      in daily medical practice. Bedside echocardiographic examination has become
      useful to properly trained cardiologists, anesthesiologists, intensivists,
      surgeons, and emergency room physicians. Cardiac ultrasound can permit rapid,
      accurate, and noninvasive diagnosis of a broad range of acute cardiovascular
      pathologies. Although transesophageal echocardiography was once the principal
      diagnostic approach using ultrasound to evaluate intensive care unit patients,
      advances in ultrasound imaging, including harmonic imaging, digital acquisition,
      and contrast for endocardial enhancement, has improved the diagnostic yield of
      transthoracic echocardiography. Ultrasound devices continue to become more
      portable, and hand-carried devices are now readily available for bedside
      applications. This article discusses the application of bedside echocardiography
      in the intensive care unit. The emphasis is on echocardiography and
      cardiovascular diagnostics, specifically on goal-directed bedside cardiac
      ultrasonography.

PMID- 17446785
TI  - Ultrasound in the management of thoracic disease.
AB  - Using simple and standardized semiology, the lung appears accessible to
      ultrasound, despite previous opinions otherwise. Lung ultrasound allows the
      intensivist to quickly answer to a majority of critical situations. Not only
      pleural effusion but also pneumothorax, alveolar consolidation, and interstitial
      syndrome will have accurate ultrasound equivalents, the recognition of which
      practically guides management. Combined with venous, cardiac, and abdominal
      examination, ultrasound investigation of this vital organ provides a transparent
      overview of the critically ill, a kind of stethoscope for a visual medicine. It
      is believed that by using this tool, the intensivist may more confidently manage
      acute dyspnea and make emergency therapeutic decisions based on reproducible
      data. Further benefits include reduced requirements for computed tomographic
      scans, therefore decreasing delay, irradiation, cost, and above all, discomfort
      to the patient. Thus, ultrasound of the lung can also be added to the classic
      armamentarium as a clinical tool for emergency use.

PMID- 17446786
TI  - Point-of-care ultrasound: Infection control in the intensive care unit.
AB  - Ultrasound provides a diagnostic modality that allows a whole-body approach at
      the bedside of a critically ill patient in the search for infectious foci. Both
      common sites of infection, such as the lung and pleura, central veins, and
      maxillary sinuses, and also less common sites, such as gastrointestinal
      perforation, sepsis due to mesenteric ischemia, or even meningitis, provide
      characteristic ultrasound patterns. Optimal use of ultrasound also combines
      bedside diagnosis with subsequent interventional procedures that can decrease the
      need for transfer to other imaging and interventional suites. Experience has
      shown that fevers of unknown origin in the critical care unit often have
      ultrasound equivalents. Thus, if a comprehensive ultrasound examination is
      negative, it is now appropriate to speak of fever of unknown sonographic origin.

PMID- 17446787
TI  - Ultrasound imaging techniques for regional blocks in intensive care patients.
AB  - Ultrasound imaging techniques have gained great popularity in anesthesia during
      the last decade. They have been shown to allow better quality of regional blocks,
      improving the outcome of patients and reducing the costs at the same time, for
      two major reasons. First, ultrasound imaging provides information of the
      individual anatomic structure and abnormalities before puncture. Second, the
      ultrasound-guided puncture is displayed in real time, and this enables the
      physician to correct the direction of the needle, both to improve the spread of
      local anesthetics and to avoid tissue damage. Ultrasound imaging allows control,
      even in difficult cases and in situations with variations of normal anatomy. Even
      positioning dependent variations of nerve roots can be managed most effectively.
      In addition, the time can be reduced considerably to perform regional blocks; the
      onset time is shorter, and the quality of blocks is better. So, ultrasound
      imaging techniques are routinely applied in the University Clinics Bergmannsheil,
      Bochum, Germany.

PMID- 17446788
TI  - Ultrasound applications in mass casualties and extreme environments.
AB  - A mass-casualty incident is one in which the number of patients with injuries
      exceeds the available medical resources to care for them in a timely manner. In
      such a situation, the numerous advantages of ultrasonography make it an ideal
      triage tool for helping clinicians rapidly screen patients. Experiences during
      the 1988 Armenian earthquake and the 1999 Turkish earthquake demonstrated the
      proficiency of ultrasound in providing rapid clinical data to the physicians
      caring for the mass-casualty patients. Wireless and satellite transmission of
      ultrasound images also has been shown to be feasible and may be applied to mass
      casualty situations. In addition, ultrasound applications have been demonstrated
      to aid in the diagnosis of various conditions, including pneumothorax, in the
      International Space Station. Ultrasound's portability, reproducibility, accuracy,
      and ease of use will make it an important diagnostic instrument for future space
      missions.

PMID- 17446789
TI  - Contrast ultrasound in the assessment of patients presenting with suspected
      cardiac ischemia.
AB  - Echocardiography is a portable technology that can be used to assess myocardial,
      pericardial, and valvular structure and function. Doppler echocardiography
      provides the ability to evaluate blood flow in large vessels and within cardiac
      chambers. Recently, the advent of microbubble contrast agents, which can opacify
      the systemic circulation, has improved the ability of echocardiography to
      evaluate left-ventricular function by improving delineation of the left
      ventricular endocardial border. Furthermore, these microbubbles can be used to
      assess myocardial perfusion and quantify myocardial blood flow. Myocardial
      contrast echocardiography has been studied in multiple clinical situations,
      including the acute evaluation of patients presenting with suspected cardiac
      ischemia. Ongoing research is focused on the development of microbubbles that are
      capable of detecting molecular and cellular events within the circulation, which
      may allow distinction of acute vs. remote ischemic insults to the myocardium.
      This multifaceted technology promises to be of increasing clinical utility--not
      only for the heart, but for any organ accessible to ultrasound.

PMID- 17446790
TI  - Toward an ultrasound curriculum for critical care medicine.
AB  - Accurate assessment and rapid decision-making are essential to save lives and
      improve performance in critical care medicine. Real-time point-of-care ultrasound
      has become an invaluable adjunct to the clinical evaluation of critically ill and
      injured patients both for pre- and in-hospital situations. However, a high level
      of quality is necessary, guaranteed by appropriate education, experience,
      credentialing, quality control, continuing education, and professional
      development. Although educational recommendations have been proposed by a variety
      of nonimaging specialties, to date they are still scattered and limited examples
      of standards for critical and intensive care professionals. The challenge of
      providing adequate specialty-specific training, as encouraged by major medical
      societies, is made even more difficult by the diversity of critical care
      ultrasound utilization by various subspecialties in a variety of settings and
      numerous countries. In order to meet this educational challenge, a standard core
      curriculum is presented in this manuscript. The proposed curriculum is built on a
      competence, performance, and outcomes-based approach that is tailored to setting
      specific training needs and prioritized according to critical problem-based
      pathways, rather than traditional organ-based systems. A multiple goal-oriented
      style fully addresses the specialty-specific approach of critical and intensive
      care professionals, who typically deal with disease states in complex scenarios
      rather than individual organ complaints. Because of the variation in the concept
      of what constitutes critical care worldwide, and the rate of change of
      information and technology, this manuscript attempts to present a learning system
      addressing a variety of needs for a rapidly changing world.

PMID- 17446791
TI  - Future directions and conclusions.
AB  - The current practice of critical care ultrasound worldwide and the potential that
      ultrasound holds for critical care patients is exciting and more advanced than
      many in the field would have suspected. This supplement has described a wide
      breadth of critical care ultrasound application that is unlikely to all be
      practiced by just one physician anywhere in the world. The urgency of
      incorporating ultrasound into critical care practice is almost palpable after
      reading the chapters making up this supplement, and the proposed curriculum will
      provide intensivists with a detailed roadmap for training. The future of critical
      care ultrasound will include development of protocols that cannot be derived from
      current traditional imaging practices and much research is still ahead of us.

PMID- 17446792
TI  - CUORE: a sustainable cardiovascular disease prevention strategy.

PMID- 17446793
TI  - Gender-specific issues in cardiac rehabilitation: do women with ischaemic heart
      disease need specially tailored programmes?
AB  - Ischaemic heart disease (IHD) has changed from a disease of middle-aged men in
      the late 1970s to a disease of elderly women in the 2000s. Most clinical studies
      during the past three decades have been conducted with men. Cardiac
      rehabilitation programmes were also developed with special regard to improving
      the rate of return to work in middle-aged men. The rehabilitation needs of older
      patients and women in particular have been largely neglected. The aim of this
      review is briefly to outline our present knowledge on gender issues in cardiac
      rehabilitation, and to specify barriers with regard to physical activities
      especially in (older) women. Coping with a cardiac event, women tend to minimize
      or play down the impact of their health situation and avoid burdening their
      social contacts. After a first cardiac event, women report greater psychological
      distress and lower self-efficacy and self-esteem. In addition, older age, lower
      exercise levels and reduced functional capacity or co-morbid conditions such as
      osteoporosis and urinary incontinence are barriers to physical activities in
      women with IHD. Recent studies on psychosocial intervention revealed less
      favourable results in women compared with men. These findings have not yet been
      well explained. This emphasizes our current lack of knowledge about the processes
      and determinants of successful psychosocial interventions in men and women with
      IHD. A large (European) trial on gender-specific coping styles, needs, and
      preferences of older women, and the effects of psychosocial intervention is
      proposed.

PMID- 17446794
TI  - Anthropometric indices and their relationship with diabetes, hypertension and
      dyslipidemia in Australian Aboriginal people and Torres Strait Islanders.
AB  - BACKGROUND: Australian indigenous people have a body shape and cardiovascular
      risk profiles different from that of other ethnic populations. This present study
      aims to examine the association of anthropometric indices with diabetes,
      hypertension and dyslipidemia, and to determine what indices can best predict
      these individual risk factors for the risk of cardiovascular disease (CVD).
      DESIGN: A cross-sectional study of Australian Aboriginal people and Torres Strait
      Islanders. METHODS: A total of 747 Australian Aboriginal people and 439 Torres
      Strait Islanders aged 25 years and over were examined between 1993 and 1997. Body
      weight, height, waist and hip circumferences, blood pressure, plasma glucose,
      triglycerides, total and high-density lipoprotein cholesterol were measured.
      RESULTS: The best predictor of hypertension among five anthropometric indices was
      waist : height ratio for Australian Aboriginal people and waist circumference for
      Torres Strait Islanders. Waist : hip ratio (WHR) was the best predictor for both
      diabetes and dyslipidemia in both populations. In multivariate regression
      analyses, WHR and body mass index were independently associated with the 10-year
      predicted absolute probability of coronary heart disease (CHD) for Torres Strait
      Islanders. However, overall WHR appeared to be the best predictor of the
      estimated CHD risk for both populations. CONCLUSIONS: This study shows that WHR
      was the best predictor for diabetes, dyslipidemia and absolute CHD risk in
      Australian Aboriginal people and Torres Strait Islanders. Incorporating WHR into
      routine health examinations in Australian indigenous people will enhance the
      evaluation of CVD risk.

PMID- 17446795
TI  - Rationale, design, methods and baseline characteristics of the Asklepios Study.
AB  - The Asklepios Study is a longitudinal population study focusing on the interplay
      between ageing, cardiovascular haemodynamics and inflammation in (preclinical)
      cardiovascular disease. The 2524 participants (1301 women) are a representative
      cohort of 35-55-year-old individuals, free from overt cardiovascular disease at
      study initiation, randomly sampled from the twinned Belgian communities of Erpe
      Mere and Nieuwerkerken. Baseline examinations (all single-observer, single
      device, single-site, single 2-year consecutive timeframe) include:
      questionnaires, conventional risk factors and biochemistry. Additional phenotypes
      under study include: (a) vascular structure and function: carotid and femoral
      atherosclerosis (intima-media thickness, plaque), arterial distension and
      pressure curves (brachial, carotid, femoral; wall-tracking and applanation
      tonometry); (b) cardiac structure and function. A novel aspect of the study is
      'integrated' non-invasive biomechanical assessment of cardiac, arterial and
      ventriculovascular function through a combination of modeling, fundamental
      hydraulical measurements and system identification techniques. Integrated
      phenotypes result from combining at least two sets of curves
      (flow/pressure/distension). The value of this 'integrated' haemodynamic phenotype
      in the detection, prediction and prevention of clinical cardiovascular pathology
      (atherosclerosis progression, atherothrombosis, development of heart failure)
      will be tested. A second novel aspect is the systematic determination of
      peripheral blood leukocyte telomere length as a marker for biological ageing.
      During follow-up, baseline examinations will be repeated and the incidence of
      cardiovascular events will be monitored. Sex-specific baseline risk factor and
      biochemical data are provided in the current analyses. The primary aim is to
      build a combined dataset that will act as a tool to answer a cluster of questions
      about ageing, haemodynamics and the emergence of cardiovascular disease,
      especially the incidence of atherothrombotic events and the development of
      adverse haemodynamic profiles (arterial stiffening, heart failure). The study
      will reassess current risk factors and provide a long-term base for the detection
      of novel (epi)genetic and non-genetic risk factors and for more performant risk
      stratification modalities. Within these broader goals, a constant will be to
      strive towards more fundamental mechanistic-haemodynamic insights into
      cardiovascular disease processes.

PMID- 17446796
TI  - Does diagnosis of the metabolic syndrome detect further men at high risk of
      cardiovascular death beyond those identified by a conventional cardiovascular
      risk score? The DECODE Study.
AB  - BACKGROUND: It is not known whether the metabolic syndrome detects further
      individuals at high risk of death from cardiovascular disease (CVD), beyond those
      identified by a conventional cardiovascular risk score. DESIGN: A prospective
      study. METHODS: A total of 2790 men without diabetes, aged 50-69 years from seven
      population-based European cohorts participating in the DECODE Study, were
      followed for CVD mortality over 10 years. RESULTS: Some 51% of the men had an
      estimated 10-year risk of fatal CVD under 5%, using the European SCORE project
      equation, and 22% of them had the metabolic syndrome, as defined by the National
      Cholesterol Education Program Adult Treatment Panel III. In the low-risk men, the
      hazards ratio for fatal CVD, after adjusting for age and study centre, was 2.71
      (1.33-5.51) for men with the syndrome (P<0.01) compared with men without the
      syndrome. A large waist circumference (>102 cm) carried an odds ratio of 2.24
      (1.05-4.76) in the low CVD risk men. CONCLUSIONS: Men with a low cardiovascular
      risk score and the metabolic syndrome had a significantly higher risk of fatal
      CVD than those without the syndrome. The use of the metabolic syndrome in
      clinical practice is thus justified in men, but waist circumference provided a
      simpler diagnostic tool with similar fatal CVD risk in these low-risk men. A
      large waist circumference could be used for prescreening, and could be included
      in CVD risk scores.

PMID- 17446797
TI  - Metabolic risks in individuals with normal body mass index and normal waist
      circumference.
AB  - BACKGROUND: Risk of cardiovascular diseases increases in Asian adults within the
      normal limits of body mass index and waist circumference. OBJECTIVE: To determine
      a point of body mass index and waist circumference above which the chances of
      having cardiovascular risk factors increased. METHODS: Data on anthropometric
      indices, blood pressure and biochemical measures were collected in a cross
      sectional study of 3447 participants (1781 males and 1666 females) with normal
      body mass index (19 to <25 kg/m for both sexes) and normal waist circumference
      (<102 cm for men and <88 cm for women). Metabolic abnormalities were defined on
      the basis of the standard published criteria. RESULTS: Individuals at the highest
      category of body mass index (24 to <25 kg/m) had significantly higher odds for
      having metabolic risk factors (odds ratios ranging from 1.3 to 1.6 for men and
      1.36 to 2.0 for women for different risk factors) compared with those at first
      category (19 to <20 kg/m). Furthermore, individuals at the top category of waist
      circumference (95 to <102 cm for men and 85-88 cm for women) had significantly
      higher chances of having metabolic abnormalities (odds ratios ranging from 2.6 to
      4.5 for men and 2.1 to 2.6 for women for different risk factors) compared with
      those in the first category (62 to <70 cm for men and 60 to <65 cm for women) in
      both sexes. CONCLUSION: We concluded that the cut-off points of body mass index
      and waist circumference suggested by the World Health Organization are
      inappropriate for the Tehranian urban population.

PMID- 17446798
TI  - Relationship between phytosterol levels and components of the metabolic syndrome
      in the PROCAM study.
AB  - BACKGROUND: Components of the metabolic syndrome such as hypertriglyceridemia,
      low high-density lipoprotein (HDL) cholesterol and obesity have been shown to be
      associated with increased cholesterol synthesis and reduced cholesterol
      absorption. In the present study, we measured the lathosterol/cholesterol ratio
      as an index of cholesterol synthesis and the ratios of cholestanol, campesterol
      and sitosterol to cholesterol as indices of cholesterol absorption, as well as
      components of the metabolic syndrome, in 324 men and 168 women from the PROCAM
      study, an epidemiological study in which raised sitosterol was previously
      associated with increased coronary risk. Our aim was to determine if the indices
      of cholesterol synthesis and absorption show a graded relationship with severity
      of metabolic syndrome. RESULTS: No differences were seen between men and women
      with regard to the relationship of either the lathosterol/cholesterol or the
      sitosterol/cholesterol ratios and severity of metabolic syndrome. On multiple
      regression analysis in men and women together, body mass index showed a positive
      relationship with the lathosterol/cholesterol ratio (r=0.257, P<0.001) and a
      negative relationship with the sitosterol/cholesterol ratio (r=-0.221, P<0.001).
      HDL-cholesterol showed a negative relationship with the lathosterol/cholesterol
      ratio (r=-0.166, P=0.001). Triglycerides showed a negative relationship with the
      sitosterol/cholesterol ratio (r=0.141, P=0.005). Overall, these relationships
      were graded across quintiles of HDL cholesterol, body mass index and triglyceride
      and across an index of metabolic syndrome severity (number of components
      present). Only the cholestanol/cholesterol ratio showed a graded relationship
      with estimated overall coronary risk. CONCLUSIONS: The metabolic syndrome is
      associated with increased cholesterol synthesis and reduced cholesterol
      absorption in a relationship that is graded across severity of the individual
      components of the syndrome and across an index of the severity of the metabolic
      syndrome as a whole.

PMID- 17446799
TI  - Comparison of the chronotropic response to exercise and heart rate recovery in
      predicting cardiovascular mortality.
AB  - BACKGROUND: Both an impaired capacity to increase heart rate during exercise
      testing (chronotropic incompetence), and a slowed rate of recovery following
      exercise (heart rate recovery) have been shown to be associated with all-cause
      mortality. It is, however, unknown which of these responses more powerfully
      predicts risk, and few data are available on their association with
      cardiovascular mortality or how they are influenced by beta-blockade. METHODS:
      Routine symptom-limited exercise treadmill tests performed on 1910 male veterans
      at the Palo Alto Veterans Affairs Medical Center from 1992 to 2002 were analyzed.
      Heart rate was determined each minute during exercise and recovery. Chronotropic
      incompetence was defined as the inability to achieve > or =80% of heart rate
      reserve, using a population-specific equation for age-predicted maximal heart
      rate. An abnormal heart rate recovery was considered to be a decrease of <22
      beats/min at 2 min in recovery. Cox proportional hazards analyses including
      pretest clinical data, chronotropic incompetence, heart rate recovery, the Duke
      Treadmill Score (abnormal defined as <4), and other exercise test responses were
      performed to determine their association with cardiovascular mortality. RESULTS:
      Over a mean follow-up of 5.1+/-2.1 years, there were 70 deaths from
      cardiovascular causes. Both abnormal heart rate recovery and chronotropic
      incompetence were associated with higher cardiovascular mortality, a lower
      exercise capacity, and more frequent occurrence of angina during exercise. Both
      heart rate recovery and chronotropic incompetence were stronger predictors of
      risk than pretest clinical data and traditional risk markers. Multivariately,
      chronotropic incompetence was similar to the Duke Treadmill Score for predicting
      cardiovascular mortality, and was a stronger predictor than heart rate recovery
      [hazard ratios 3.0 (95% confidence interval 1.9-4.9), 2.8 (95% confidence
      interval 1.7-4.8), and 2.0 (95% confidence interval 1.1-3.5) for abnormal Duke
      Treadmill Score, chronotropic incompetence, and abnormal heart rate recovery,
      respectively]. Having both chronotropic incompetence and abnormal heart rate
      recovery strongly predicted cardiovascular death, resulting in a relative risk of
      4.2 compared with both responses being normal. Beta-blockade had minimal impact
      on the prognostic power of chronotropic incompetence and heart rate recovery.
      CONCLUSION: Both chronotropic incompetence and heart rate recovery predict
      cardiovascular mortality in patients referred for exercise testing for clinical
      reasons. Chronotropic incompetence was a stronger predictor of cardiovascular
      mortality than heart rate recovery, but risk was most powerfully stratified by
      these two responses together. The simple application of heart rate provides
      powerful risk stratification for cardiovascular mortality from the exercise test,
      and should be routinely included in the test report.

PMID- 17446800
TI  - Asymmetric dimethyl-arginine and coronary artery calcification in young adults
      entering middle age: the CARDIA Study.
AB  - BACKGROUND: Normal endothelial function depends on nitric oxide (NO) release by
      endothelial cells. Asymmetric dimethylarginine (ADMA), by competing with L
      arginine, inhibits NO production and may lead to endothelial dysfunction and
      atherosclerotic development. Our aim was to ascertain the association between
      ADMA and coronary artery calcification (CAC), a marker of atherosclerotic
      coronary disease burden. DESIGN: A nested case-control study within the Coronary
      Artery Risk Development in Young Adults (CARDIA) cohort, an observational study
      among young adults residing in four US cities. METHODS: Participants were 263
      white and black male and female cases with the presence of CAC and 263 sex and
      race-matched controls without evidence of CAC by computed tomography, 33-47 years
      old in 2000-2001. RESULTS: The median level (range) of ADMA was significantly
      higher in cases (0.55; 0.20-2.22 micromol/l) than in controls (0.53; 0.32-1.30
      micromol/l; P=0.03). In conditional logistic regression adjusting for age, field
      center, educational attainment, smoking status, alcohol consumption, body mass
      index, waist circumference, hypertension, diabetes, low-density lipoprotein and
      high-density lipoprotein-cholesterol, triglycerides, renal function and C
      reactive protein, the highest tertile of ADMA, compared with the lowest tertile,
      was associated with 1.80 (95% confidence interval 1.03-3.15) increased odds of
      the presence of any CAC. By linear regression, a significant independent
      relationship was also found between ADMA and the degree of CAC. CONCLUSION: These
      results support a role for ADMA as a biochemical marker of CAC.

PMID- 17446801
TI  - Type 2 diabetes mellitus and risk of coronary heart disease: results of the 10
      year follow-up of the PROCAM study.
AB  - BACKGROUND: American and European consensus opinions recommend that diabetes
      mellitus be regarded as a 'coronary risk equivalent', that is, as conferring the
      same risk of myocardial infarction as established coronary heart disease. We
      examined if this holds true for men in the Prospective Cardiovascular Munster
      Study (PROCAM). DESIGN: We conducted a single-centre, prospective,
      epidemiological study, calculating risk using the PROCAM calculator, which takes
      diabetes mellitus into account, in men at work in public authorities and large
      companies in the region of Munster, Germany. PARTICIPANTS: Five thousand, three
      hundred and eighty-nine men aged 35-65 years at recruitment participated, 3778 of
      whom were normoglycaemic, 1205 of whom displayed impaired fasting glycaemia, and
      406 of whom suffered from diabetes mellitus. Coronary events (fatal or nonfatal
      myocardial infarction, sudden coronary death) occurring within 10 years of
      unbroken follow-up were assessed. RESULTS: Of men with diabetes mellitus 13.3%
      suffered a coronary event within 10 years, compared with 7.3% of men with
      impaired fasting glycaemia, and 5.3% of normoglycaemic men. Using the PROCAM risk
      calculator, only 26.5% of the men with diabetes mellitus were calculated to have
      a 10-year coronary event risk at or above the threshold of 20% (high risk)
      regarded as being equivalent to the risk conferred by established coronary heart
      disease. Eight percent of men with impaired fasting glycaemia and 5.5% of
      normoglycaemic men were at high risk. The positive predictive value of a high
      risk estimate was 35% in men with diabetes, 32% in men with impaired fasting
      glycaemia, and 31% in normoglycaemic men. CONCLUSION: In PROCAM, less than a
      third of men with diabetes were classified as being at high risk of coronary
      events. It is therefore incorrect to regard the presence of diabetes mellitus as
      a coronary risk equivalent.

PMID- 17446802
TI  - Impaired postexercise cardiovascular autonomic modulation in middle-aged women
      with type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes is associated with cardiovascular autonomic
      dysfunction. Postexercise autonomic modulation may be different in obese
      individuals with and without type 2 diabetes. We examined postexercise responses
      in nondiabetic and diabetic women aged 40-60 years. METHODS: Hemodynamics, high
      frequency and low-frequency of RR interval, low-frequency of systolic blood
      pressure variability and baroreflex sensitivity were evaluated before and after a
      20 min walk at approximately 65% of VO2 peak in eight lean, 12 obese without type
      2 diabetes and eight women with type 2 diabetes. Postexercise measurements were
      obtained at 10-15, 20-25 and 30-35 min. RESULTS: Systolic blood pressure
      decreased at 10 (P<0.001) and 20 min (P<0.01) in all groups. Total peripheral
      resistance decreased at 10 min in all women, but the subsequent increase at 20
      min was greater (P<0.01) in lean than in diabetic women. Log-transformed low
      frequency of systolic blood pressure increased (P<0.01) at 10 and 20 min in all
      women, but the increase at 10 min was smaller (P<0.05) in diabetic than in lean
      women. Heart rate was increased (P<0.001) at 10 min in all women and at 20 min in
      both obese groups. Both log-transformed high-frequency of RR interval and
      baroreflex sensitivity decreased at 10 and 20 min of recovery in all groups. A
      group-by-time interaction (P<0.05) was observed for heart rate and baroreflex
      sensitivity as a lower heart rate and higher baroreflex sensitivity were observed
      in lean women than in women with type 2 diabetes. CONCLUSIONS: Reduced
      postexercise baroreflex sensitivity and responses to autonomic cardiovascular
      activity contribute to an attenuated recovery of heart rate and total peripheral
      resistance after brisk walking in middle-aged obese women with type 2 diabetes.

PMID- 17446803
TI  - Smoking cessation and risk of type 2 diabetes mellitus: Korea Medical Insurance
      Corporation Study.
AB  - BACKGROUND: To investigate the independent effects of smoking cessation on the
      risk for developing type 2 diabetes mellitus (DM) in the general population.
      DESIGN: An 8-year prospective study. METHODS: This prospective study started with
      baseline examinations in 1990 and 1992, and continued with follow-up examinations
      every 2 years up to 1998 and 2000. A total of 27 635 nondiabetic men, aged 35-44
      years were classified as 5701 nonsmokers, 7477 ex-smokers and 14 457 sustained
      smokers, based on repeated self-reported questionnaires in 1992, 1994 and 1996.
      Baseline fasting serum glucose level and other risk factors were measured in 1990
      and 1992. The outcome was newly developed DM, defined as a fasting glucose level
      > or =7.0 mmol/l in 1998 and 2000 (averaged). RESULTS: Over the 8 years, 1170 men
      (4.2%) developed DM. When compared with nonsmokers, the fully adjusted risk ratio
      of ex-smokers and sustained smokers for diabetes was 1.22 [95% confidence
      interval (CI), 0.96-1.55] and 1.60 (95% CI, 1.29-1.97), respectively. Among the
      ex-smokers, the risk for diabetes differed according to the quit-smoking period.
      Compared with nonsmokers, the fully adjusted risk ratio for DM in men who quit
      smoking before 1992, during 1992-1993 and during 1994-1995 was 0.95 (0.72-1.25),
      1.44 (0.96-2.15) and 2.13 (1.51-3.00), respectively, after adjustment for age,
      baseline fasting serum glucose, weight change, baseline body mass index, family
      history of DM, alcohol consumption and exercise status. CONCLUSIONS: Our results
      support cigarette smoking as an independent and modifiable risk factor for DM.
      Early smoking cessation could decrease the risk for developing DM to that of
      nonsmokers in the long term.

PMID- 17446804
TI  - Coronary collateral flow in response to endurance exercise training.
AB  - BACKGROUND: In humans, it is not known whether physical endurance exercise
      training promotes coronary collateral growth. The following hypotheses were
      tested: the expected collateral flow reduction after percutaneous coronary
      intervention of a stenotic lesion is prevented by endurance exercise training;
      collateral flow supplied to an angiographically normal coronary artery improves
      in response to exercise training; there is a direct relationship between the
      change of fitness after training and the coronary collateral flow change. METHODS
      AND RESULTS: Forty patients (age 61+/-8 years) underwent a 3-month endurance
      exercise training program with baseline and follow-up assessments of coronary
      collateral flow. Patients were divided into an exercise training group (n=24) and
      a sedentary group (n=16) according to the fact whether they adhered or not to the
      prescribed exercise program, and whether or not they showed increased endurance
      (VO2max in ml/min per kg) and performance (W/kg) during follow-up versus baseline
      bicycle spiroergometry. Collateral flow index (no unit) was obtained using
      pressure sensor guidewires positioned in the coronary artery undergoing
      percutaneous coronary intervention and in a normal vessel. In the vessel
      initially undergoing percutaneous coronary intervention, there was an increase in
      collateral flow index among exercising but not sedentary patients from 0.155+/
      0.081 to 0.204+/-0.056 (P=0.03) and from 0.189+/-0.084 to 0.212+/-0.077 (NS),
      respectively. In the normal vessel, collateral flow index changes were from
      0.176+/-0.075 to 0.227+/-0.070 in the exercise group (P=0.0002), and from 0.219+/
      0.103 to 0.238+/-0.086 in the sedentary group (NS). A direct correlation existed
      between the change in collateral flow index from baseline to follow-up and the
      respective alteration of VO2max (P=0.007) and Watt (P=0.03). CONCLUSION: A 3
      month endurance exercise training program augments coronary collateral supply to
      normal vessels, and even to previously stenotic arteries having undergone
      percutaneous coronary intervention before initiating the program. There appears
      to be a dose-response relation between coronary collateral flow augmentation and
      exercise capacity gained.

PMID- 17446805
TI  - Coronary flow velocity reserve reduction is comparable in patients with erectile
      dysfunction and in patients with impaired fasting glucose or well-regulated
      diabetes mellitus.
AB  - BACKGROUND: There is growing evidence that erectile dysfunction is a sentinel for
      future coronary artery disease. Recently published studies have shown signs of
      impaired coronary endothelial function in patients with erectile dysfunction,
      without clinical cardiovascular disease and diabetes. We evaluated the magnitude
      of coronary vasodilatory dysfunction in men with erectile dysfunction, as
      compared with men with impaired glucose metabolism (impaired fasting glucose or
      diabetes) and healthy controls. METHODS: We investigated men aged 68-73 years
      with erectile dysfunction (n=12), age-matched men with impaired glucose
      metabolism, who all proved to have erectile dysfunction (n=15), and age-matched
      male controls (n=12). Erectile dysfunction was evaluated using the International
      Index of Erectile Function (IIEF)-5 questionnaire. Coronary flow velocity reserve
      in the left anterior descending artery was examined using Doppler ultrasound and
      intravenous adenosine provocation. RESULTS: Coronary flow velocities at rest did
      not differ between the three groups, but maximum coronary flow velocity was
      significantly lower in the erectile dysfunction group (P=0.004) and in the
      impaired glucose metabolism group (P=0.019), as compared with controls. There was
      no difference between the erectile dysfunction and impaired glucose metabolism
      groups. Coronary flow velocity reserve was reduced in the erectile dysfunction
      group (P=0.026) compared to controls, but was similar compared to the impaired
      glucose metabolism group. In multivariate analysis including all groups, erectile
      dysfunction score was the only independent predictor of reduced coronary flow
      velocity reserve (P=0.020). CONCLUSIONS: The magnitude of early coronary
      endothelial and smooth muscle cell dysfunction in otherwise healthy men with
      erectile dysfunction was comparable to that of patients with impaired glucose
      metabolism: a well known risk factor for coronary artery disease.

PMID- 17446806
TI  - Plant stanol esters are potentially cost-effective in the prevention of coronary
      heart disease in men: Bayesian modelling approach.
AB  - BACKGROUND: Plant stanol esters in spreads have demonstrated efficacy in reducing
      serum cholesterol. The cost-effectiveness of plant stanol esters in the
      prevention of coronary heart disease, however, has remained unevaluated. DESIGN:
      A Bayesian modelling approach was applied to synthesize clinical evidence and
      evaluate the cost-effectiveness (Euro/quality-adjusted life years) of plant
      stanol esters in spread in the prevention of coronary heart disease based on
      published FINRISK and 4S risk functions. RESULTS: The regular use of plant stanol
      esters reduced total serum cholesterol by -0.362 mmol/l [95% credibility interval
      (CrI) -0.31 to -0.41]. The corresponding placebo-adjusted reduction attributable
      to stanol esters when combined with statin was -0.385 mmol/l (95% CrI -0.18 to 
      0.61). The cost-effectiveness estimations were assessed for men and women
      separately at four different initial ages at which the regular use of stanol
      esters was assumed to be started. The base case cost per quality-adjusted life
      years gained by using stanol esters regularly ranged from 7436 to 20,999 Euro in
      men and from 34,327 to 112,151 Euro in women based on the initial starting age.
      According to uncertainty analysis, there is over a 90% probability that the use
      of plant stanol esters is cost-effective for men inclusively and for 60-year-old
      and older women assuming that decision-makers' maximum willingness to pay per
      quality-adjusted life year is 50,000 Euro. CONCLUSIONS: A recommendation that
      plant stanol ester-containing spreads be used as a part of daily diet replacing
      regular spread could be viewed as potentially cost-effective public health policy
      in the prevention of CHD in all adult men and in older age-groups of women with
      total serum cholesterol levels of 5 mmol/l or greater.

PMID- 17446807
TI  - Noncardiac chest pain in the emergency department: the role of cardiac history,
      anxiety or depression and Type D personality.
AB  - BACKGROUND: Noncardiac chest pain is common in patients presenting to emergency
      departments and is frequently associated with panic disorder. This can represent
      a major burden for patients and the healthcare system. Little is known about the
      patient characteristics that increase the risk of noncardiac chest pain. We
      examined whether cardiac history or Type D personality was associated with panic
      disorder and/or depression-driven noncardiac chest pain. METHODS AND RESULTS:
      Patients presenting with noncardiac chest pain to the emergency department of the
      University Hospital Maastricht were screened using the Hospital Anxiety and
      Depression Scale (HADS). Patients scoring > or =8 on the HADS subscale were
      invited for a psychiatric interview; a consecutive sample of patients scoring <8
      on the HADS was included as a reference group. Type D personality (tendency to
      experience emotional distress) was assessed with the DS14. Among the 304 HADS
      positive patients, 89% were diagnosed with panic disorder/depression as compared
      with 8% of the 106 HADS-negative patients. Previous cardiac history was not
      associated with psychiatric diagnosis. Type D patients reported more anxiety
      symptoms (12.4+/-4.0 vs. 8.1+/-4.9) and depression symptoms on the HADS (10.2+/
      4.7 vs. 5.8+/-4.9) and more often had comorbid panic disorder/depression
      (91/157=58% vs. 57/253=23%) than non-Type D patients (P<0.0001). Type D
      personality (odds ratio =8.67, 95% confidence interval 4.69-16.02), younger age
      and male sex were independently associated with increased risk of panic disorder
      or depression. Type D was independently associated with comorbid panic
      disorder/depression (odds ratio=14.49). CONCLUSION: Type D personality, but not
      cardiac history, is independently associated with the presence of psychopathology
      in noncardiac chest pain. Type D is associated with a substantially increased
      risk of co-occurring PD/depression in these patients.

PMID- 17446808
TI  - Survival in relation to angina symptoms and diagnosis among men aged 70-90 years:
      the Whitehall Study.
AB  - BACKGROUND: While the excess mortality associated with a diagnosis of angina,
      myocardial infarction in middle-aged individuals is well established, there is
      little available evidence on the natural history of angina in population-based
      studies of older people. DESIGN: We conducted a 5-year follow-up of 6655 older
      men aged 67-90 years (mean age 77 years) who participated in the Whitehall Study
      of London Civil Servants. METHODS: Survival was examined in relation to a
      diagnosis of angina or myocardial infarction and to angina symptoms in a
      population-based study of older men living in the United Kingdom in the late
      1990s. RESULTS: Compared with men without a diagnosis of myocardial ischaemia
      (n=5219), a diagnosis of angina alone (n=617), myocardial infarction alone
      (n=421) or both (n=398) were associated with about a threefold, fourfold and
      sixfold higher risk of death from coronary heart disease, respectively. Median
      expectation of life at age 70 years was reduced by about 2, 5 and 6 years for
      those with angina, myocardial infarction, or both, respectively. Current symptoms
      of angina among those without previously diagnosed angina, was associated with a
      2-fold higher risk of coronary heart disease mortality than those without either
      diagnosis or symptoms. CONCLUSIONS: Both angina symptoms and diagnosis have a
      significant adverse effect on survival among men aged 70-90 years highlighting
      the importance of diagnosis and appropriate treatment of angina in old age.

PMID- 17446809
TI  - Physical activity levels in adults with congenital heart disease.
AB  - BACKGROUND: Regular physical activity is associated with many health benefits in
      patients with cardiac disease. Advances in treatment have resulted in an
      increasing population of adults with congenital heart disease. Few data are
      available on physical activity levels and attitude to exercise in this group.
      DESIGN: Prospective, cross-sectional study of patients attending the adult
      congenital heart disease clinic in a supra-regional centre. METHODS: Physical
      activity assessed over 1 week using two accelerometers. The Actigraph was used to
      measure total activity volume and intensity and the Caltrac used to measure
      energy expenditure in physical activity. Patients completed a questionnaire to
      assess exercise self-efficacy. RESULTS: In all, 61 adults recruited (36 male;
      mean-age 31.7+/-10.9 years); divided into three groups according to New York
      Heart Association class [Group I (n=26; 14 male), Group II (n=18; 10 male), Group
      III (n=17; 11 male)]. Fourteen patients were overweight (body mass index 25-29.9)
      and seven obese (body mass index>30). Group 1 achieved similar activity levels to
      a sedentary reference population. Group II and III had significantly lower
      activity (55 and 40% of Group I). Most study patients failed to achieve UK
      national guidelines for physical activity (Groups I: 77%, II: 84%, III: 100%).
      Despite this, questionnaire responses suggested a willingness to participate in
      exercise in the majority of each group. CONCLUSIONS: Adults with congenital heart
      disease have a range of physical activity levels between normal and severely
      limited. Most patients showed a willingness to participate in exercise but were
      uncertain of the safety or benefit. Intervention to increase physical activity
      levels may be a low risk, low cost treatment strategy.

PMID- 17446810
TI  - Effects of movement and work load in patients with congenital central
      hypoventilation syndrome.
AB  - BACKGROUND: Patients with congenital central hypoventilation syndrome lack
      ventilatory chemosensitivity and depend at least in part on the ergoreceptor
      function during exercise. In these patients a substantial increase of ventilation
      has been reported for passive movement during sleep as well as active movement on
      a treadmill. OBJECTIVES: The aim of the study was to investigate ventilatory
      response to an increasing work load with constant movement. METHODS AND RESULTS:
      Eighteen patients and 17 healthy volunteers performed a cardiopulmonary exercise
      test on a bicycle pedaling at a constant rate of about 60 revolutions per minute
      throughout the entire test. The patients were able to exercise adequately and
      showed normal peak oxygen uptake. There was a steep rise in minute ventilation in
      both groups at the start of exercise, yet there was only a minor increase in both
      groups during the increase of workload up to the anaerobic threshold. After the
      anaerobic threshold, there was again an increase in ventilation in both groups,
      but the increase was less prominent in the patient group. CONCLUSIONS:
      Ventilation in patients with congenital central hypoventilation syndrome is
      increased during exercise caused both by movement (mechanoreceptors) and by
      anaerobic workload. This facilitates a normal ventilatory drive up to the
      anaerobic threshold and a normal exercise capacity in these patients.

PMID- 17446811
TI  - Tar yield and risk of acute myocardial infarction: pooled analysis from three
      case-control studies.
AB  - BACKGROUND: Controversial information is available with reference to the role of
      type or yield of cigarettes on the risk of cardiovascular disease. DESIGN: We
      considered the issue in a combined dataset of three case-control studies of acute
      myocardial infarction conducted in Italy between 1983 and 2003. METHODS: Cases
      were 1990 subjects with a first episode of non-fatal acute myocardial infarction,
      and controls were 2521 patients in hospital for acute diseases unrelated to
      smoking or other recognized risk factors for myocardial infarction. The odds
      ratio and the corresponding 95% confidence interval (CI) were derived by
      unconditional multiple logistic regression models, including terms for age, sex,
      and several major risk factors for myocardial infarction. RESULTS: As compared to
      never smokers, the multivariate odds ratio was 2.70 (95% CI 2.01-3.63) for
      smokers of low tar cigarettes (<10 mg), 3.06 (95% CI 2.53-3.70) for intermediate
      (10-19 mg) and 3.14 (95% CI 2.12-4.64) for high tar yield (> or =20 mg). After
      further allowance for duration of smoking and number of cigarettes per day, as
      compared to low tar yield cigarettes, the odds ratio was 1.14 (95% CI 0.85-1.53)
      for intermediate, and 1.28 (95% CI 0.81-2.02) for high tar yield. CONCLUSION: Our
      study confirms that no substantial reduction in acute myocardial infarction risk
      resulted from the decrease of cigarette tar yield.

PMID- 17446812
TI  - The effects of exercise training on the kinetics of oxygen uptake in patients
      with chronic heart failure.
AB  - BACKGROUND: Prolonged oxygen uptake kinetics (O2 kinetics), following the onset
      of a constant workload of exercise has been associated with a poor prognosis in
      patients with chronic heart failure. This study aimed to determine both
      continuous and interval training effects on the different O2-kinetics phases in
      these patients. DESIGN: Twenty-one patients (60+/-8 years) with stable chronic
      heart failure participated in a 36-session exercise rehabilitation program (three
      times weekly). Patients were randomly assigned to interval training (n=11; 100%
      of peak work rate for 30 s, alternating with 30 s-rest) and to continuous
      training (n=10; 50% of peak work rate). METHODS: Before and after the completion
      of the program, all patients performed both incremental symptom-limited and
      constant workload submaximal cardiopulmonary exercise tests. Phase I O2-kinetics
      was evaluated by time (t), from the start of exercise until the onset of
      decreased respiratory exchange ratio and phase II by the time constant (tau) of
      the response from the end of phase I until steady state. RESULTS: After training,
      there was a significant increase in peak oxygen uptake and peak work rate in both
      continuous (15.3+/-4.4 vs. 16.6+/-4.5 ml/kg per min; P=0.03 and 81.8+/-40.1 vs.
      94.7+/-46.1 W; P=0.03) and interval training groups (14.2+/-3.1 vs. 15.4+/-4.2
      ml/kg per min; P=0.03 and 82.5+/-24.1 vs. 93.7+/-30.1 W; P=0.04). Patients who
      underwent interval training had a significant decrease in t (39.7+/-3.7 to 36.1+/
      6.9 s; P=0.05), but not tau (59.6+/-9.4 to 58.9+/-8.5 s; P=ns), whereas those
      assigned to continuous training had a significant decrease in both t (40.6+/-6.1
      to 36.4+/-5.4 s; P=0.01) and tau (63.3+/-23.6 to 42.5+/-16.7 s; P=0.03).
      CONCLUSIONS: Exercise training improves O2 kinetics in chronic heart failure
      patients. Both continuous and interval training improve phase I O2-kinetics, but
      continuous training results in superior improvement of the phase II O2-kinetics,
      an indirect index of muscle oxidative capacity.

PMID- 17446813
TI  - Renal function and outcomes in acute coronary syndrome: impact of clopidogrel.
AB  - INTRODUCTION: Patients with renal dysfunction are more prone to bleeding when
      receiving antithrombotic drugs. The aim of the study was to assess the impact of
      clopidogrel on safety and efficacy in patients with renal dysfunction in non-ST
      elevation acute coronary syndromes. METHODS AND RESULTS: Patients in the
      Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial were
      analysed to assess the relationship of chronic kidney disease to cardiovascular
      outcomes. Renal function was estimated by the glomerular filtration rate computed
      from the baseline serum creatinine measurements in 12 253 (97.5%) patients
      enrolled in the trial. Patients were grouped into tertiles of glomerular
      filtration rate. The primary outcome (cardiovascular death, myocardial
      infarction, stroke combined) occurred more frequently in the lowest glomerular
      filtration rate tertile. The bleeding risk was also significantly increased in
      patients in this tertile, compared with the other two. The beneficial effect of
      adding clopidogrel to standard treatment in non-ST elevation acute coronary
      syndrome was observed in all three tertiles of renal function {(lower third
      relative risk (RR)=0.89 [95% confidence interval (CI) 0.76-1.05]; medium third
      RR=0.68 (95% CI 0.56-0.84); upper third RR=0.74 (95% CI 0.60-0.93) (P for
      heterogeneity=0.11)}. Clopidogrel treatment significantly increased the risk of
      minor bleeding in all tertiles of renal function. The risk of major or life
      threatening bleeding increased moderately with the addition of clopidogrel to
      standard treatment [lower third RR=1.12 (95% CI 0.83-1.51); medium third RR=1.4
      (95% CI 0.97-2.02); upper third RR=1.83 (95% CI 1.23-2.73)], but this did not
      appear to be greatest in those with the lowest renal function. CONCLUSIONS: Even
      mild chronic kidney disease worsens the prognosis in patients with non-ST
      elevation acute coronary syndromes. Clopidogrel was beneficial and safe in
      patients with and without chronic kidney disease.

PMID- 17446814
TI  - Nitric oxide synthase type-1 modulates cardiomyocyte contractility and calcium
      handling: association with low intrinsic aerobic capacity.
AB  - BACKGROUND: The neuronal isoform of nitric oxide synthase (NOS-1) may be an
      important regulator of cardiac contractility by modifying calcium release and
      uptake from sarcoplasmic reticulum. Our working hypothesis was that NOS-1
      modulates cardiomyocyte contractility more markedly in rat lines with low versus
      high congenital aerobic fitness. METHODS AND RESULTS: Rats performed high
      intensity interval treadmill running 5 days per week over 8 weeks; age-matched
      sedentary rats served as controls. At baseline before the training program,
      aerobic fitness measured as maximal oxygen uptake was 30% higher, and
      cardiomyocyte contractility measured as fractional shortening 42% higher in high
      than in low congenital aerobic fitness rats. Training markedly increased aerobic
      fitness as well as cardiomyocyte contractility, relaxation and corresponding
      changes in calcium transient in both lines. Selective inhibition of NOS-1
      increased cardiomyocyte contractility (12-43%) and calcium transient amplitude
      (10-28%), prolonged time to 50% relengthening (13-52%) and time to 50% calcium
      decay (17-35%), in all groups. Interestingly, NOS-1-inhibition abolished the
      difference in systolic events between low and high congenital aerobic fitness
      whereas no such findings occurred in diastolic parameters. CONCLUSION: NOS-1
      derived nitric oxide production is a modulator of cardiomyocyte contractile
      performance and calcium handling in rats. It accounts for some of the difference
      between rats with low versus high congenital aerobic fitness, whereas it
      contributes little during adaptation to exercise training.

PMID- 17446815
TI  - Impact of time trends and increasing age on health behaviour of Swedish school
      children.
AB  - BACKGROUND: Information on trends in healthy and unhealthy habits among children
      are important for the development of programmes intended to foster and
      consolidate a healthy lifestyle. This report studied the importance of time and
      age on the health behaviour of Swedish school children. METHODS: A comparison
      between health behaviours derived from repeated evaluations of Swedish school
      children aged 11-13 years was performed. RESULTS: Significant positive time
      trends were found in the form of increased physical activity and decreased
      sedentary behaviours, whereas negative time trends were observed in dietary
      habits and smoking. An analysis of the impact of increasing age demonstrated a
      negative influence including less physical activity and deteriorating dietary
      habits and increased smoking at the young age groups in this study. CONCLUSION:
      Time trends and age are both important determinants of health behaviour in pre
      teen children. Even the small age increase from 11 to 13 years had an important
      negative influence. The results of the present study underline that the window of
      opportunities to promote a healthy lifestyle in children is narrow. It is evident
      that a successful health intervention programme must be initiated at an early
      age, continued and repeated over time, and structured to counteract trends in age
      as well as time.

PMID- 17446816
TI  - Prevention of coronary heart disease with statins in UK South Asians and
      Caucasians.
AB  - AIMS: To determine the prevalence of subjects eligible for primary and secondary
      prevention of coronary heart disease (CHD) among the British South Asian
      population and to compare that with British Caucasians. METHODS AND RESULTS: We
      used the Health Survey for England 1998 and 1999 datasets, holding data on 9950
      Caucasians and 1938 South Asians. Thresholds for treatment were a total
      cholesterol >3.5 mmol/l and either a history of cardiovascular disease or
      elevated estimated CHD risk, adjusted where necessary for ethnic differences.
      Separate analyses were performed for primary prevention risk thresholds of >15%
      and >30% over 10 years. The prevalence of previous myocardial infarction, angina,
      or stroke was higher in South Asian men than in Caucasian but the reverse was
      seen in women. More than 93% [95% confidence interval (CI) 88-97] of South Asian
      men and nearly 68% (95% CI 66-71) of Caucasian men older than 55 years have a CHD
      risk greater than 15% (equivalent to cardiovascular risk of 20%) and a
      cholesterol above 3.5 mmol/l and would be eligible for treatment with lipid
      lowering drugs. The equivalent proportions in women are 55% (95% CI 46-65) and
      18% (95% CI 16-20) in South Asians and Caucasians, respectively. CONCLUSION:
      Treating this proportion of the population will have a societal impact, the
      majority of older people becoming patients, and although it may well be cost
      effective for individuals, it will require substantial new resources.

PMID- 17446817
TI  - Averting a pandemic health crisis in Europe by 2020: what physicians need to know
      regarding cholesterol management.
AB  - BACKGROUND: Cardiovascular disease (CVD) represents a major cause of premature
      death, disability, and escalating healthcare costs throughout Europe. According
      to a recent report by the Stockholm Network (an independent European 'think
      tank'), major political, economic, social, and medical changes are urgently
      needed with respect to cholesterol management to help prevent CVD. METHODS: To
      identify key cholesterol management issues that practitioners should consider to
      help prevent an impending European health crisis, our collective experience of
      policies and practices relating to CVD and cholesterol management in our
      respective countries was consolidated and used to develop this commentary.
      RESULTS: Physicians and healthcare workers are uniquely positioned to make
      immediate and meaningful improvements in preventing and treating CVD if they
      recognize and address a handful of key clinical issues pertaining to cholesterol
      management. These issues include utilizing newer combination therapies and
      realizing the limitations of statins, improving compliance with cholesterol
      lowering therapies, promoting a healthy lifestyle and diet, making treatment
      decisions based on patients' total CVD risk, fostering communication between
      primary and secondary providers, and soliciting governmental funding to implement
      disease management programmes. CONCLUSIONS: By promptly and effectively
      addressing these cholesterol management issues, physicians and other healthcare
      professionals have an unprecedented opportunity to help reduce CVD in Europe to
      lessen the personal, social, and economic impact of this devastating disease.

PMID- 17446818
TI  - Short stature, abdominal obesity, insulin resistance and alterations in lipid
      profile in very low-income women living in Maceio, north-eastern Brazil.
AB  - OBJECTIVE: To test the hypothesis that short stature is associated with abdominal
      obesity, insulin resistance and lipid profile changes. METHODS: Anthropometric
      data were collected from 237 women (18-60 years old), residents of a shantytown
      in Maceio. Biochemical profiles of 60 individuals drawn from this population were
      determined. RESULTS: Total and low-density lipoprotein (LDL) cholesterol levels
      and insulin resistance rose with increasing waist : hip circumference ratio,
      particularly in women. Short, overweight individuals exhibited larger biochemical
      alterations than overweight individuals of average stature. CONCLUSION: Short
      stature, when associated with overweight, is a risk factor for increased insulin
      resistance and alterations in lipid profile.

PMID- 17446819
TI  - Atherosclerosis lifestyle risk factors in children with congenital heart disease.
AB  - OBJECTIVE: To assess lifestyle risk factors for atherosclerotic cardiovascular
      disease in children with congenital heart disease. MATERIALS AND METHODS: Surveys
      were distributed to 329 unselected cardiac children. RESULTS: Many patients were
      taking an unhealthy diet and did not eat fruit (68%), vegetables (60%) or low-fat
      milk products (60%) every day, whereas 41% drank sweetened beverages and 89% ate
      foods high in fats at least three times a week. Only 15% spent half an hour daily
      involved in after-school physical activity, whereas 7.6% were overweight, 4.3%
      had arterial hypertension, 50% were passive smokers and 12% of teenagers were
      active smokers. CONCLUSION: Most cardiac children have modifiable cardiovascular
      risk factors. This highlights the importance of enhancing actions to promote a
      healthy lifestyle addressed to that population.

PMID- 17446821
TI  - The implantable cardiac defibrillator: is the glass half empty or half full?

PMID- 17446822
TI  - Toward a better understanding of the role of geography in intensity of end-of
      life care: must we first come to an understanding of end-of-life care?

PMID- 17446823
TI  - Health-related quality of life consequences of implantable cardioverter
      defibrillators: results from MADIT II.
AB  - BACKGROUND: Implantable cardioverter defibrillators (ICDs) improve survival and
      extend lives of patients with severe heart disease. OBJECTIVE: We sought to
      evaluate the impact of ICDs on health-related quality of life (HRQOL) during the
      first 3 years after implantation. SUBJECTS: A total of 1089 patients from the
      Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) were
      randomized to an ICD or medical treatment only. MEASURES: Health Utility Index
      (HUI3) at baseline, 3, 12, 24, and 36 months following randomization; survival
      data. RESEARCH DESIGN: We constructed mean profiles of HRQOL for living patients,
      estimated overall quality-adjusted life years (QALYs), separately by treatment
      arm, and calculated cumulative QALY gains/losses as the difference between the
      areas under the treatment specific HRQOL profiles. Multivariate fixed effect
      regression models were developed to impute the missing HRQOL data using baseline
      patient characteristics (age, gender, treatment, HUI3 score, diabetes, diuretics
      use, and NYHA class). Bootstrapped standard errors were calculated for the
      estimated differences in HRQOL gains/losses between treatment arms. Similarly, we
      performed subgroup analyses (by gender, age, and baseline NYHA class, blood urine
      nitrogen, ejection fraction, and QRS). RESULTS: There were no differences in
      QALYs loss for living patients by treatment group (-0.037, P = 0.64) or in
      overall QALYs loss by treatment group (0.043, P = 0.37) over 3 years. In subgroup
      analysis, female subjects demonstrated a trend towards greater survival benefit
      (0.298, P = 0.07) and overall QALYs (0.261, P = 0.14). CONCLUSIONS: Adverse
      effects of the ICD on HRQOL together with lower HRQOL among survivors may offset
      the 3-year survival benefits of ICDs.

PMID- 17446824
TI  - Are regional variations in end-of-life care intensity explained by patient
      preferences?: A Study of the US Medicare Population.
AB  - OBJECTIVE: We sought to test whether variations across regions in end-of-life
      (EOL) treatment intensity are associated with regional differences in patient
      preferences for EOL care. RESEARCH DESIGN: Dual-language (English/Spanish) survey
      conducted March to October 2005, either by mail or computer-assisted telephone
      questionnaire, among a probability sample of 3480 Medicare part A and/or B
      eligible beneficiaries in the 20% denominator file, age 65 or older on July 1,
      2003. Data collected included demographics, health status, and general
      preferences for medical care in the event the respondent had a serious illness
      and less than 1 year to live. EOL concerns and preferences were regressed on
      hospital referral region EOL spending, a validated measure of treatment
      intensity. RESULTS: A total of 2515 Medicare beneficiaries completed the survey
      (65% response rate). In analyses adjusted for age, sex, race/ethnicity,
      education, financial strain, and health status, there were no differences by
      spending in concern about getting too little treatment (39.6% in lowest spending
      quintile, Q1; 41.2% in highest, Q5; P value for trend, 0.637) or too much
      treatment (44.2% Q1, 45.1% Q5; P = 0.797) at the end of life, preference for
      spending their last days in a hospital (8.4% Q1, 8.5% Q5; P = 0.965), for
      potentially life-prolonging drugs that made them feel worse all the time (14.4%
      Q1, 16.5% Q5; P = 0.326), for palliative drugs, even if they might be life
      shortening (77.7% Q1, 73.4% Q5; P = 0.138), for mechanical ventilation if it
      would extend their life by 1 month (21% Q1, 21.4% Q5; P = 0.870) or by 1 week
      (12.1% Q1, 11.7%; P = 0.875). CONCLUSIONS: Medicare beneficiaries generally
      prefer treatment focused on palliation rather than life-extension. Differences in
      preferences are unlikely to explain regional variations in EOL spending.

PMID- 17446825
TI  - How do patients with colorectal cancer perceive treatment and care compared with
      the treating health care professionals?
AB  - BACKGROUND: Patient evaluations are widely used in quality assessment of health
      services. It is widely recognized that patients and professionals provide a
      different perspective on quality. However, the extent to which they differ and
      the conceptual areas in which they differ is not well understood. OBJECTIVES: We
      sought to examine how well professional and patient assessments of hospital
      health care correspond. METHODS: We undertook a prospective study in which
      information from a national clinical register was combined with questionnaires to
      patients, surgeons, and nurses. The study included 527 patients after surgery for
      colorectal cancer. The patients and their professionals assessed the same
      questions. For 336 patients, all questionnaires and register information were
      available. The response rate was 64%. The main measures were assessments of
      technical, interpersonal, and organizational aspects of care. Agreement was
      analyzed by kappa statistic, kappa, and McNemar's test. RESULTS: Comparing
      assessments of technical surgical care kappa statistic demonstrated moderate-to
      almost perfect agreement (0.35 <or= kappa <or= 0.95). Assessments of technical
      nursing care demonstrated slight agreement (0.19 <or= kappa <or= 0.26). Comparing
      answers to questions on interpersonal or organizational care, kappa statistic
      revealed only slight or no more agreement than expected by chance (-0.06 <or=
      kappa <or= 0.30). For several items, McNemar's test revealed a significant
      difference in the distribution of answers. CONCLUSIONS: Within a Danish
      population undergoing treatment of colorectal cancer, there were significant
      differences in perceptions of care between patients and health professionals. In
      particular, health professionals and readers of reports on patient evaluations
      ought to remember that patients' perspective is just one source of information in
      assessment of hospital health care.

PMID- 17446826
TI  - Treatment choice and quality of care for men with localized prostate cancer.
AB  - BACKGROUND: Variations in patterns of care and treatment outcomes suggest
      differences in the quality of care for men treated for localized prostate cancer.
      OBJECTIVE: We sought to compare adherence with quality indicators for prostate
      cancer care among men treated with radical prostatectomy or external beam
      radiation therapy. RESEARCH DESIGN AND SUBJECTS: We sampled 5230 men diagnosed in
      2000 or 2001 with early-stage prostate cancer from 984 facilities reporting to
      the National Cancer Data Base. Our analytic cohort includes 2604 men (from 770
      facilities) treated with radical prostatectomy or external beam radiation. MAIN
      OUTCOME MEASURE: Subject-level compliance with the RAND quality indicators for
      localized prostate cancer care, stratified by treatment. We applied sampling
      weights to obtain national estimates of quality indicator adherence. RESULTS: The
      weighted samples represent 24,547 and 27,125 men treated with radical
      prostatectomy or external beam radiation therapy, respectively. Compliance with
      several quality indicators approached 100% in both treatment groups; however
      treatment-specific variations were noted. Men receiving radiation were less
      likely than those undergoing surgery to be treated in facilities with a board
      certified urologist (odds ratio [OR] = 0.4, 95% confidence interval [95% CI] =
      0.2-0.8). Adherence with process of care indicators was appreciably higher among
      radiation subjects, including documentation of clinical stage (OR = 7.5, 95% CI =
      4.8-11.9), pretherapy assessment of urinary (OR = 2.8, 95% CI = 1.9-4.2) and
      sexual (OR = 1.6, 95% CI = 1.2-2.2) function, and discussion of treatment options
      (OR = 1.8, 95% CI = 1.1-2.9). CONCLUSIONS: Documented compliance with process of
      care quality indicators among men with localized prostate cancer appears superior
      for those treated with external beam radiation compared with those treated
      surgically.

PMID- 17446827
TI  - Diagnosis of advanced cancer among elderly Medicare and Medicaid patients.
AB  - BACKGROUND: Medicaid is implicated in late-stage cancer diagnoses, which is the
      primary indicator of a poor prognosis. OBJECTIVE: We examined Medicaid enrollment
      and cancer diagnosis in patients ages 66 years and older. Medicaid enrollment was
      defined as enrolled 12+ months before diagnosis, enrolled <12 months before
      diagnosis, and enrolled after diagnosis. SUBJECTS: Medicaid and Medicare
      administrative data were merged with the Michigan Tumor Registry to extract a
      sample of 46,109 patients with a first primary diagnosis of prostate, lung,
      breast, or colorectal cancer between 1997 and 2000. Measures were: (1) diagnosed
      during the same month as death; (2) invasive, but unknown stage; and (3) regional
      or distant stage disease. RESULTS: : Patients enrolled in Medicaid <12 months
      before diagnosis were at greater risk of breast (odds ratio [OR] = 2.70; 95%
      confidence interval [95% CI] = 1.22-5.99) and lung (OR = 2.18; 95% CI = 1.45
      3.29) cancer diagnosis in the month of death than Medicare only patients.
      Similarly, patients with a history of Medicaid enrollment had a high risk of
      diagnosis with invasive, but unknown breast, lung, and prostate cancer stage.
      Patients enrolled in Medicaid following diagnosis had a higher risk of late stage
      colorectal (OR = 1.30; 95% CI = 1.01-1.67), breast (OR = 2.12; 95% CI = 1.60
      2.82), and lung (OR = 1.33; 95% CI = 1.02-1.75) cancer relative to Medicare only
      patients. CONCLUSIONS: There is a preponderance of cancer diagnosis at death and
      cancer diagnosis with invasive but unknown stage in the Medicaid population, but
      the appropriateness of these diagnoses is unclear. Late-stage cancer tends to
      precipitate Medicaid enrollment.

PMID- 17446828
TI  - Differences among the elderly in the treatment costs of colorectal cancer: how
      important is race?
AB  - BACKGROUND: Medical expenditures adjusted for price differences are a barometer
      of total resources devoted to patient care and thus may reflect treatment
      differentials. OBJECTIVE: We sought to estimate costs of the surgical and
      adjuvant treatment phases of colorectal cancer (CRC) care and cost differences by
      race (African American-white) and other patient characteristics. METHODS: We used
      the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database
      for stage II-III rectal and stage III colon cancer cases diagnosed in 1992-1996
      to track Medicare approved payments for fee-for-service beneficiaries 66 and
      older in surgical (within 3 months of diagnosis) and postsurgical phases (13
      months after the surgical phase). Net costs adjusted for expected noncancer
      expenditures were estimated with generalized linear models using pooled CRC and
      non-CRC cohorts. Using model results, we projected adjusted net costs for
      different patient groups (eg, by race, age). RESULTS: Total unstandardized CRC
      costs for African American recipients were $44,199, a statistically significant
      15% higher than for white recipients ($38,378). Adjusting for covariates and
      expected non-CRC costs decreased the estimate for African American recipients to
      $34,588, a statistically insignificant $974 (2.9%) more than white recipients.
      Differential expenditures by age, urban-rural setting, region, and neighborhood
      median income were all much larger than differences by race, although only region
      was statistically significant. CONCLUSIONS: African American CRC patients cost
      more than their white counterparts, but adjusted differences were nonsignificant
      and trivial. Several nonracial cost differences were considerably larger (but not
      all statistically significant), and suggest that future research pay more
      attention to these characteristics.

PMID- 17446829
TI  - Patient centered experiences in breast cancer: predicting long-term adherence to
      tamoxifen use.
AB  - BACKGROUND: Among breast cancer patients, tamoxifen use is associated with
      reduced risk of disease relapse and death, but it is often difficult for women to
      sustain therapy during the 5 years required to obtain maximum benefit.
      OBJECTIVES: We sought to examine the influence of patient-centered care
      activities on ongoing tamoxifen use 4 years after initiation, we examined key
      components of patient-centered care and rates of ongoing tamoxifen. METHODS:
      Using a prospective cohort study that included observational data from the
      National Initiative for Cancer Care Quality (NICCQ), we studied 881 patients with
      stage I-III breast cancer who were registered with an initial diagnosis in 1998
      by an American College of Surgeons-approved hospital cancer registry in 1 of 5
      metropolitan areas, who initiated tamoxifen treatment. A patient survey and
      medical record abstraction were used as measurements. RESULTS: Among women who
      initiated tamoxifen, 79% were still taking it 4 years later. Other than older age
      and the severity of side effects, other demographic, clinical and cancer
      characteristics, and treatments did not predict ongoing tamoxifen use. In
      contrast, after adjusting for these factors, the proportion of patients with
      ongoing tamoxifen use was lower for patients reporting less support than needed
      (82% vs. 69%, P = 0.0051), less than wanted role in decision-making (80% vs. 70%,
      P = 0.0486), decision-making about tamoxifen without doctor input (79% vs. 64%, P
      = 0.0182), and for patients who weren't told about side effects in advance (82%
      vs. 72%, P = 0.0016). CONCLUSIONS: Although age and the severity of side-effects
      remain important, patient-centered care was a primary mediator of patient
      adherence to ongoing cancer treatment with tamoxifen.

PMID- 17446830
TI  - Predictors of aggressive therapy for nonmetastatic prostate carcinoma in
      Massachusetts from 1998 to 2002.
AB  - BACKGROUND: Most studies have found that black men are less likely to receive
      aggressive therapy for nonmetastatic prostate cancer, even after controlling for
      covariates. However, previous studies have not accounted for the clustering of
      outcomes by facility. OBJECTIVE: We sought to compare the proportions of black
      and white men receiving aggressive therapy for newly diagnosed nonmetastatic
      prostate cancer between 1998 and 2002, accounting for the clustering of outcomes
      by facility. METHODS: We used the Massachusetts Cancer Registry of all cancer
      diagnosed in residents of Massachusetts. We used logistic regression, clustering
      by the facility where the tumor was diagnosed, to predict the probability that a
      patient would receive any aggressive therapy, and the specific therapeutic
      choices of radical prostatectomy, external-beam radiation therapy, and
      brachytherapy. Predictors included race, age, poverty, insurance status, marital
      status, year of diagnosis, and tumor grade. RESULTS: Black men were similarly
      likely to receive aggressive therapy compared with white men (odds ratio [OR]
      0.79, 95% confidence interval [CI] 0.62-1.01). However, there was a racial
      difference in the receipt of particular types of therapy: black men were
      significantly more likely to receive radiation therapy (OR 1.39, 95% CI 1.16
      1.68) and less likely to receive radical prostatectomy (OR 0.53, 95% CI 0.38
      0.74). CONCLUSIONS: Among men diagnosed with nonmetastatic prostate cancer in
      Massachusetts from 1998 to 2002, black men received aggressive therapy at rates
      approaching those of whites. However, they were more likely to receive radiation
      therapy and less likely to receive radical prostatectomy.

PMID- 17446831
TI  - Hospital workload and adverse events.
AB  - CONTEXT: Hospitals are under pressure to increase revenue and lower costs, and at
      the same time, they face dramatic variation in clinical demand. OBJECTIVE: : We
      sought to determine the relationship between peak hospital workload and rates of
      adverse events (AEs). METHODS: A random sample of 24,676 adult patients
      discharged from the medical/surgical services at 4 US hospitals (2 urban and 2
      suburban teaching hospitals) from October 2000 to September 2001 were screened
      using administrative data, leaving 6841 cases to be reviewed for the presence of
      AEs. Daily workload for each hospital was characterized by volume, throughput
      (admissions and discharges), intensity (aggregate DRG weight), and staffing
      (patient-to-nurse ratios). For volume, we calculated an "enhanced" occupancy rate
      that accounted for same-day bed occupancy by more than 1 patient. We used Poisson
      regressions to predict the likelihood of an AE, with control for workload and
      individual patient complexity, and the effects of clustering. RESULTS: One urban
      teaching hospital had enhanced occupancy rates more than 100% for much of the
      year. At that hospital, admissions and patients per nurse were significantly
      related to the likelihood of an AE (P < 0.05); occupancy rate, discharges, and
      DRG-weighted census were significant at P < 0.10. For example, a 0.1% increase in
      the patient-to-nurse ratio led to a 28% increase in the AE rate. Results at the
      other 3 hospitals varied and were mainly non significant. CONCLUSIONS: Hospitals
      that operate at or over capacity may experience heightened rates of patient
      safety events and might consider re-engineering the structures of care to respond
      better during periods of high stress.

PMID- 17446832
TI  - Pharmacist workload and pharmacy characteristics associated with the dispensing
      of potentially clinically important drug-drug interactions.
AB  - BACKGROUND: Drug-drug interactions (DDIs) are preventable medical errors, yet
      exposure to DDIs continues despite systems that are designed to prevent such
      exposures. The purpose of this study was to examine pharmacy characteristics that
      may be associated with dispensed potential DDIs. METHODS: This study combined
      survey data from community pharmacies in 18 metropolitan statistical areas with
      pharmacy claims submitted to 4 pharmacy benefit managers (PBMs) over a 3-month
      period from January 1, 2003 to March 31, 2003. Pharmacy characteristics of
      interest included prescription volume, the number of full-time equivalent
      pharmacists and pharmacy staff, computer software programs, and the ability to
      modify those programs with respect to DDI alerts, the use of technologies to
      assist in receiving, filling and dispensing medication orders, and prescription
      volume. The dependent variable in this study was the rate of dispensed
      medications that may interact. RESULTS: A total of 672 pharmacies were included
      in the analysis. On average (+/-SD), the respondents filled 1375 +/- 691
      prescriptions per week, submitted 17,948 +/- 23,889 pharmacy claims to the
      participating PBMs, had 1.2 +/- 0.3 full-time equivalent pharmacists per hour
      open, and 545 (81%) were affiliated with a chain drug store organization. Factors
      significantly related to an increased risk of dispensing a potential DDI included
      pharmacist workload (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.028
      1.048), pharmacy staffing (OR 1.10; 95% CI: 1.09-1.11), and various technologies
      (eg, sophisticated telephone systems, internet receipt of orders, and refill
      requests) that assist with order processing, and the ability to modify DDI alert
      screening sensitivity and detailed pharmacological information about DDIs.
      CONCLUSIONS: This study found that there was an increase in the risk of
      dispensing a potential DDI with higher pharmacist and pharmacy workload, use of
      specific automation, and dispensing software programs providing alerts and
      clinical information.

PMID- 17446833
TI  - The impact of a quality improvement program on systems, processes, and structures
      in medical clinics.
AB  - OBJECTIVE: We sought to assess whether participation in a quality-improvement
      collaborative changed care processes, systems, and organization of outpatient
      human immunodeficiency virus (HIV) clinics. METHODS: We surveyed clinicians,
      medical directors, and HIV program administrators before and after an 18-month
      quality improvement collaborative at 54 intervention and 37 control clinics
      providing HIV care. Surveys assessed clinic structures, processes, systems, and
      culture. During the collaborative, a clinician-administrator team from each
      intervention clinic attended 4 2-day sessions on quality improvement techniques.
      Conference calls, a website, and an e-mail list provided support and facilitated
      communication among collaborative participants. RESULTS: Survey response rates
      were 85% or greater. Six of 54 organizational measures differed significantly
      between baseline and follow-up. Intervention clinicians reported greater computer
      availability (82% vs. 67%, P = 0.03) and use (3.13 vs. 2.68, P = 0.02; 4-point
      scale), attended more local (14.2 vs. 8.6, P < 0.01) and national (4.1 vs. 2.9, P
      = 0.01) conferences, and rated leaders' ability to implement quality improvement
      higher (3.8 vs. 3.4, P = 0.01; 5-point scale). Intervention directors were more
      likely to compare quality data to other clinics (79% vs. 54%, P = 0.04). For the
      set of 54 measures, intervention clinics were more likely to have higher post
      intervention scores than controls (sign test, mean = 14.5, P < 0.0001).
      CONCLUSIONS: A quality-improvement collaborative for HIV clinics resulted in
      modest organizational changes. Achieving greater change may require more focused
      and/or intensive interventions, greater resources for participating clinics, and
      better developed information technology.

PMID- 17446834
TI  - Potentially inappropriate medication use and healthcare expenditures in the US
      community-dwelling elderly.
AB  - BACKGROUND: Potentially inappropriate medication (PIM) use is a major source of
      drug-related problems in the elderly. Few studies have quantified the effect of
      PIM use on total healthcare expenditures in the United States. OBJECTIVES: : We
      sought to determine the relationship between PIM use and healthcare expenditure
      and to estimate the annual incremental healthcare expenditures related to PIM use
      in the community-dwelling elderly population in the United States in 2001.
      METHODS: This was a retrospective cohort study. Participants were age 65 years or
      older who had no PIM use in rounds 1 and 2 of the 2000-2001 Medical Expenditure
      Panel Survey, a nationally representative survey of the US noninstitutionalized
      population. On the basis of the 2002 Beers criteria, PIM users were identified as
      those who had been prescribed at least one PIM during specified time periods in
      the study. Propensity scores were used to match PIM users and nonusers in the
      analysis examining differences in total healthcare expenditures. RESULTS: PIM
      utilization is a significant predictor for higher healthcare expenditures (P <
      0.05). A conservative estimate of the incremental healthcare expenditures related
      to PIM use in the community-dwelling elderly population would be $7.2 billion
      (95% confidence interval, $3.4 billion-$15.7 billion) in the United States in
      2001. CONCLUSIONS: PIM use is a major patient safety concern that results in
      increased healthcare expenditures. This study emphasizes the need for continued
      provider education to inform prescribers of the potential risks of using certain
      medications in the elderly and to improve prescribing practices.

PMID- 17446835
TI  - Photodynamic therapy for pancreatic cancer.
AB  - OBJECTIVES: This study examined the status of photodynamic therapy (PDT) in the
      treatment of cancers of the pancreas. METHODS: Original and review articles,
      editorials, and case reports published primarily in English and listed in
      Medline/ISI up to October 2006 or identified by a manual search have been
      reviewed in an attempt to provide a comprehensive overview of the mechanisms of
      PDT action and clinical application of PDT in the treatment of pancreatic
      cancers. RESULTS: Photodynamic therapy represents a novel treatment of pancreatic
      malignancy; it produces local necrosis of tissue with light after administration
      of a photosensitizing agent. Evidences from in vivo and in vitro results have
      shown that PDT significantly decreases pancreatic cancer cell growth, destroys
      pancreatic carcinoma, and prolongs the survival of patients with unresectable
      pancreatic malignancy, and also show that PDT has disadvantages and limitations
      for the treatment of pancreatic cancer. CONCLUSIONS: Photodynamic therapy can be
      an effective treatment of patients with pancreatic cancer, but more extensive
      preclinical and clinical trials are needed for further improvement in the
      clinical application of PDT, especially in avoidance of complications during PDT.

PMID- 17446836
TI  - Pancreatitis: prevalence and risk factors among male veterans in a detoxification
      program.
AB  - OBJECTIVES: To determine the prevalence of pancreatitis and associated risk
      factors among heavy-drinking veterans. METHODS: At a large Veterans
      Administration Outpatient Detoxification Program (ODP) that systematically
      collects risk information, 1409 black and white male veterans with International
      Classification of Diseases, Ninth Revision codes for alcohol abuse enrolling in
      the ODP from January 2002 to December 2003 were identified. Among these patients,
      pancreatitis at any time (before the ODP admission or occurring through June
      2005) was identified using International Classification of Diseases, Ninth
      Revision codes. Cases were verified by chart review. Logistic regression analyses
      were used for multivariable analyses. RESULTS: Overall, history of smoking
      (89.6%) and current or past drug use (90.1%) were very common, whereas
      intravenous drug use (22.3%) was less so. Although 87 (6.2%) subjects had
      pancreatitis codes (acute, 50; chronic, 15; both, 22), chart review verified only
      42 cases (acute, 29; chronic, 5; both, 8) for a 3% prevalence. Alcohol appeared
      to be the definite etiology in 39 of these 42 patients. In bivariate analyses,
      patients with pancreatitis were older, had more substance abuse admissions,
      reported a significantly heavier current alcohol use, and lower drug dependence
      (each P < 0.05). In multivariable models, alcoholic pancreatitis was associated
      positively with age (odds ratio, 1.08; 95% confidence interval, 1.04-1.12) and
      number of substance abuse admissions (odds ratio, 1.08; 95% confidence interval,
      0.995-1.18; P = 0.06). CONCLUSIONS: In this high-risk population of heavy
      drinkers, the prevalence of pancreatitis is at least 3%. Our study provides
      preliminary data regarding potential cofactors for pancreatitis in heavy
      drinkers.

PMID- 17446837
TI  - The efficacy of nonsurgical treatment of infected pancreatic necrosis.
AB  - OBJECTIVES: We conducted this study to evaluate the efficacy of nonsurgical
      treatment for patients with infected pancreatic necrosis (IPN). METHODS: Among
      224 patients with acute pancreatitis from 2000 to 2004, there were 31 patients
      diagnosed as having IPN complication. The diagnostic criteria for IPN were either
      a positive culture or free gas in the pancreas of patients with acute pancreatic
      necrosis. Nonsurgical management including percutaneous drainage or endoscopic
      drainage (ED) followed by vigorous irrigation was initially attempted in all
      patients. Surgery was planned only when there was no clinical improvement after
      the initial nonsurgical treatment. RESULTS: Percutaneous drainage or ED was
      performed in 18 and 5 patients, respectively. Eight patients received antibiotics
      only. Four patients (12.9%) (3 from percutaneous drainage group and 1 from ED
      group) required surgery. Sepsis or fistula developed in 32% and 6% of patients,
      respectively, and was managed successfully. One patient (3.2%) died as a result
      of rapidly progressing multiorgan failure. The mean duration of hospitalization
      was 37 days. During the follow-up period, 7 patients were readmitted because of
      fever; they were managed by reposition of the drainage tube. CONCLUSIONS:
      Intensive nonsurgical treatment is very effective and safe and should be
      considered as an initial treatment modality for patients with IPN.

PMID- 17446839
TI  - Protective effects of vascular endothelial growth factor on intestinal epithelial
      apoptosis and bacterial translocation in experimental severe acute pancreatitis.
AB  - OBJECTIVES: Bacterial translocation (BT) plays an important role in systemic
      complications in severe acute pancreatitis (SAP). We recently demonstrated that
      accelerated apoptosis of intestinal mucosa might have a role in BT. Effects of
      vascular endothelial growth factor (VEGF) on intestinal epithelial cell apoptosis
      and BT were investigated in SAP. METHODS: Severe acute pancreatitis was induced
      by retrograde injection of sodium deoxycholate into the biliopancreatic duct in
      rats. Recombinant rat VEGF (2 microg) was injected, and SAP was immediately
      induced. Eight hours after the induction, serum amylase/lipase levels and
      apoptosis of ileal mucosa were evaluated. After 18 hours, the villous height of
      ileum was examined. After 22 hours, hematocrit, pancreatic water content, BT to
      the mesenteric lymph nodes, plasma plasminogen activator inhibitor 1 levels, and
      microvessel density in the small intestine were investigated. RESULTS:
      Amylase/lipase levels were significantly elevated in SAP, but VEGF did not affect
      them. Apoptosis of ileal mucosa was accelerated in SAP, and VEGF significantly
      reduced the apoptosis. Villous height was significantly decreased in SAP, and
      VEGF significantly improved it. Vascular endothelial growth factor did not affect
      the hematocrit or pancreatic water content. Bacterial translocation occurred in
      the SAP group, and VEGF significantly prevented that. Plasminogen activator
      inhibitor 1 levels were significantly elevated in SAP, and VEGF significantly
      improved the elevation. Microvessel counts were significantly reduced in SAP, and
      VEGF significantly increased them. CONCLUSION: These results suggest that VEGF
      inhibits intestinal epithelial cell apoptosis and subsequent BT in SAP.

PMID- 17446838
TI  - Disialotransferrin, determined by capillary electrophoresis, is an accurate
      biomarker for alcoholic cause of acute pancreatitis.
AB  - OBJECTIVES: Serum disialotransferrin is a specific marker of heavy alcohol
      consumption. We tested its accuracy and probability in detecting alcoholic cause
      of acute pancreatitis (AP). METHODS: Blood samples from 271 consecutive AP
      patients, admitted to the Helsinki University Central Hospital emergency unit,
      were analyzed. RESULTS: The median (range) disialotransferrin value was
      significantly higher (P = 0.001) in AP patients with alcoholic (n = 172) 1.6%
      (0.3%-14.4) than with biliary (n = 60) 0.7% (0.3%-1.3%) or other causes (n = 39)
      0.8% (0.3%-4.1%). In receiver operating curve analysis, disialotransferrin, as a
      single analyte, was significantly (P = 0.001-0.0001) more accurate (area under
      the curve [AUC], 0.88; 95% confidence interval [CI], 0.84-0.92) in detecting
      alcoholic AP as compared with glutamyl transferase (AUC, 0.51; 95% CI, 0.45
      0.57), aspartate aminotransferase (AUC, 0.57; 95% CI, 0.51-0.63), alanine
      aminotransferase (AUC, 0.63; 95% CI, 0.57-0.69), erythrocyte mean cell volume
      (AUC, 0.72; 95% CI, 0.67-0.78), amylase (AUC, 0.74; 95% CI, 0.67-0.78), C
      reactive protein (AUC, 0.65; 95% CI, 0.59-0.71), and bilirubin (AUC, 0.55; 95%
      CI, 0.49-0.62). At a disialotransferrin cutoff of 1.2%, giving an 8% false
      positive rate, the positive likelihood ratio was 8.47. Thus, a positive
      disialotransferrin test result, performed within 24 hours of admission, increased
      the probability of alcoholic AP from pretest 64% to posttest 94%. CONCLUSIONS:
      Disialotransferrin, determined by capillary electrophoresis, is accurate, simple,
      and a rapid single biomarker of the alcoholic cause of AP.

PMID- 17446840
TI  - Decreased serum leptin concentration in patients with chronic pancreatitis.
AB  - OBJECTIVE: Previously reported data suggest that serum leptin concentration
      changes in some acute and chronic inflammatory diseases. The aim of the present
      study was to assess serum leptin concentration in patients with chronic
      pancreatitis. METHODS: Forty-four male patients with chronic pancreatitis and 16
      healthy (male) subjects were examined. Fasting blood samples were collected from
      patients and healthy controls. Serum leptin and insulin concentrations were
      determined by radioimmunoassay method. RESULTS: Significantly lower serum leptin
      concentration in patients with chronic pancreatitis than in healthy subjects was
      found. No significant difference in serum leptin concentration between patients
      without and with exacerbation of chronic pancreatitis on admission was observed.
      Moreover, patients with chronic pancreatitis had (a) lower serum insulin
      concentration, (b) higher serum glucose concentration, and (c) lower body mass
      index than healthy subjects. CONCLUSION: The results presented in this article
      indicate that chronic pancreatitis in humans is associated with the decrease in
      serum leptin concentration. One can suppose that the decrease in serum insulin
      concentration, maldigestion, and fat loss all contribute to the decrease of serum
      leptin concentration in chronic pancreatitis.

PMID- 17446841
TI  - N34S mutation in the SPINK1 gene is not associated with alternative splicing.
AB  - OBJECTIVES: Previous studies have shown an association between chronic
      pancreatitis (CP) and mutations, especially the N34S mutation, in the serine
      protease inhibitor Kazal type 1 (SPINK1) gene. But the underlying molecular
      mechanisms are unknown. The aberrant splicing caused by the cosegregating
      intronic mutations might play a role, but this hypothesis has not been tested. We
      here examined the messenger RNA sequences of the SPINK1 gene in patients carrying
      the mutations. METHODS: RNA was isolated from the surgically resected pancreas of
      2 CP patients carrying the homozygous N34S mutation and from the gastric biopsy
      specimen of a CP patient carrying the heterozygous [-215G>A; IVS3+2T>C] mutation.
      The entire coding region of the SPINK1 gene was amplified by reverse
      transcription-polymerase chain reaction, subcloned, and sequenced. The level of
      the wild-type SPINK1 transcript was assessed by real-time polymerase chain
      reaction. RESULTS: Alternative splicing was not associated with the N34S
      mutation. On the other hand, the [-215G>A; IVS3+2T>C] mutation caused skipping of
      whole exon 3, where the trypsin binding site is located. This mutated protein was
      predicted to consist of 63 amino acids: deletion of amino acid sequence from
      residues 30 to 64 and shifting of reading frame at amino acid 65 with a novel
      stop codon. The expression of the wild-type SPINK1 transcript was decreased to
      62% of the healthy control in the CP patient carrying the heterozygous [-215G>A;
      IVS3+2T>C] mutation. CONCLUSIONS: Splicing mutation might represent a mechanism
      for SPINK1-associated CP, but the N34S mutation is not associated with
      alternative splicing.

PMID- 17446842
TI  - Establishment of clonal colony-forming assay for propagation of pancreatic cancer
      cells with stem cell properties.
AB  - OBJECTIVE: Pancreatic cancer is among the most aggressive solid malignancies. It
      is possible that pancreatic cancer contains cancer stem cells responsible for its
      malignancy. The purposes of this study were (1) to establish an assay in which a
      subset of pancreatic cancer cell line (PANC-1) cells with stem cell properties
      can propagate, and (2) to identify the cells obtained from this assay. METHODS:
      The PANC-1 cells were cultured in Dulbecco modified eagle medium F12 supplemented
      with epidermal growth factor, basic fibroblast growth factor, insulin,
      transferrin, selenium, and bovine serum albumin at a density of 1000 cells/mL for
      10 to 14 days to form spheres. Cells of spheres were cultured in different
      conditions to evaluate their ability of self-renewal and differentiation. Clone
      formation assay and tumor formation assay were used to identify the ability of
      propagation in vitro and in vivo. The cells and spheres were also stained by
      using Hoechst 33342 dye to evaluate their capacity of excluding Hoechst dye. Real
      time polymerase chain reaction was used to detect expressions of LY6E, c-Met,
      TACSTD1, CD34, and CD44 mRNA. RESULTS: A subpopulation of PANC-1 cells could
      propagate to form spheres in this assay. Cells of obtained spheres had the
      hallmark of excluding Hoechst 33342 dye. Cultured in serum-free medium, the
      dissociated single cells of primary spheres could form filial spheres again;
      cultured in serum-containing medium, these cells generated both the cells with
      the ability of excluding Hoechst 33342 dye and the cells without that ability.
      The propagation capacity of PANC-1 spheres was higher than that of cells cultured
      in serum-containing medium both in vitro and in vivo. In addition, LY6E, TACSTD1,
      and CD44 mRNA were overexpressed in PANC-1 spheres. CONCLUSIONS: A subpopulation
      of PANC-1 cells can propagate to form spheres with properties of stem cells in
      this assay; enough of these cells can be obtained for further study. Considering
      the overexpression of mRNA, it was tentatively suggested that LY6E, TACSTD1, and
      CD44 proteins may act as surface markers for sorting pancreatic cancer stem cells
      with fluorescence-activated cell sorter/magnetic-activated cell sorter.

PMID- 17446843
TI  - CEACAM1, a novel serum biomarker for pancreatic cancer.
AB  - OBJECTIVES: Serum biomarkers for early diagnosis of pancreatic adenocarcinoma are
      not currently available. We recently observed elevated expression of CEACAM1 in
      pancreatic adenocarcinomas and sought to determine whether serum CEACAM1 levels
      were elevated in pancreatic cancer patients. METHODS: CEACAM1 messenger RNA
      levels were measured in pancreatic tissue samples using quantitative reverse
      transcription-polymerase chain reaction. CEACAM1 was localized by
      immunohistochemistry in adenocarcinomas and in pancreatic intraductal neoplasia
      lesions. CEACAM1 serum levels were assessed by a double determinant enzyme-linked
      immunosorbent assay and compared with serum levels of CA19-9. RESULTS: CEACAM1
      had higher expression levels in pancreatic adenocarcinomas compared with
      noncancerous pancreas (P < 0.0001) and was localized to neoplastic cells (95%
      (45/47) of adenocarcinomas and 85% (17/20) of pancreatic intraductal neoplasia 3
      lesions. CEACAM1 was expressed in the sera of 91% (74/81) of pancreatic cancer
      patients, 24% (15/61) of normal patients, and 66% (35/53) of patients with
      chronic pancreatitis, with a sensitivity and specificity superior to CA19-9. The
      combination of CEACAM1 and CA19-9 had significantly higher diagnostic accuracy
      than CA19-9. CONCLUSIONS: CEACAM1 is expressed in pancreatic adenocarcinoma, and
      serum levels of CEACAM1 serve as a useful indicator for the presence of
      pancreatic cancer. Additional validation studies on the use of serum CEACAM1 as a
      diagnostic marker in pancreatic cancer are warranted.

PMID- 17446844
TI  - Vascular endothelial growth factor-C secreted by pancreatic cancer cell line
      promotes lymphatic endothelial cell migration in an in vitro model of tumor
      lymphangiogenesis.
AB  - OBJECTIVES: To investigate mechanisms underlying lymphatic node metastasis in
      pancreatic cancer, we examined roles of vascular endothelial growth factor-C
      (VEGF-C) in tumor lymphangiogenesis. METHODS: We measured VEGF-C secretion by
      pancreatic cancer cell lines using enzyme-linked immunosorbent assay and examined
      effects of different cell lines on lymphatic endothelial cells (LECs) in vitro.
      RESULTS: We identified VEGF-C high-secretion (MIA PaCa-2) and low-secretion cell
      lines (BxPC-3). The trend of enhancement of LEC proliferation by recombinant
      human VEGF-C (rVEGF-C) was not statistically significant. Numbers of migrating
      cells were increased by rVEGF-C treatment in a dose-dependent manner. The MIA
      PaCa-2 cell culture supernatant caused greater LEC migration than the BxPC-3
      supernatant. The VEGF-C effects were significantly inhibited by rVEGF receptor 3
      (rVEGF R3)/Fc chimera. In LEC/fibroblast coculture on collagen gel, LEC capillary
      formation was significantly enhanced by coculture with MIA PaCa-2 cells compared
      with BxPC-3 cells. Enhanced capillary formation with MIA PaCa-2 cells was
      inhibited by rVEGF R3/Fc chimera, implying VEGF-C involvement in progression of
      LEC sprouting in a tumor microenvironment. CONCLUSIONS: Because VEGF-C secreted
      by pancreatic cancer cells plays an important role in LEC migration in pancreatic
      cancer lymphangiogenesis, it is possible that rVEGF R3/Fc chimera might have a
      role in controlling lymph node metastasis.

PMID- 17446845
TI  - Acinar plasticity: development of a novel in vitro model to study human acinar-to
      duct-to-islet differentiation.
AB  - OBJECTIVES: The plasticity of pancreatic tissue is demonstrated in many
      pancreatic diseases. It has previously been shown that pancreatic islet-to-duct
      transformation and acinoductal metaplasia have been associated with both
      pancreatic regeneration and adenocarcinoma in various in vivo and in vitro
      settings. Understanding this inherent morphogenetic plasticity of the adult
      pancreas could lead to new therapeutic approaches to pancreatic disease. METHODS:
      Cadaveric human pancreases (n = 7) were digested, and purified acinar tissue,
      which was approximately 85% immunoreactive for amylase and approximately 15%
      immunoreactive for CK-19, was embedded in a type 1 collagen matrix and cultured
      in a differentiation medium (DM) consisting of Dulbecco modified Eagle/F12 medium
      supplemented with cholera toxin (100 ng/mL), epidermal growth factor (10 ng/mL),
      and insulin (24 mU/mL) for 8 days. After this initial period, the resulting
      tissues were cultured in DM without cholera toxin, supplemented with gastrin (50
      nmol/L) and hepatocyte growth factor (HGF; 10 ng/mL), with islet neogenesis
      associated protein (INGAP; 167 nmol/L) or with gastrin + HGF + INGAP for 6 days.
      Tissue samples were then analyzed for amylase, cytokeratin 19, pancreas duodenum
      homeobox 1, and endocrine hormone immunoreactivity as well as dithizione
      positivity. RESULTS: After 8 days of culture, approximately 90% of acini
      transformed into ductlike structures. This acinoductal transformation was
      characterized by a complete absence of amylase staining, with virtually all cells
      CK-19 immunoreactive. Addition of INGAP led to an approximately 18-fold increase
      in pancreas duodenum homeobox 1 immunoreactivity, although without an observed
      increase in insulin production as measured by dithizone positivity. However, when
      acinar-derived ductlike structures were cultured with gastrin + HGF + INGAP, the
      total incidence of dithizone-positive structures increased approximately 6-fold
      (10.9 +/- 2.9% vs 1.7 +/- 0.4%, P = 0.037). Treatment with gastrin + HGF alone
      led to no significant change in any of the measured parameters. CONCLUSIONS: We
      have developed a novel in vitro model of adult human acinoductal metaplasia that
      will aid not only in developing new methods of expanding beta-cell mass but also
      provide insights into pancreatic carcinogenesis.

PMID- 17446846
TI  - Hyperglycemia and diabetic renal change in a model of polyvinyl alcohol
      bioartificial pancreas transplantation.
AB  - OBJECTIVES: We have developed a bioartificial pancreas transplantation method
      using polyvinyl alcohol. Using this model, the relationship between hyperglycemia
      and parameters that represent renal function was investigated. METHODS: Plasma
      glucose, 1,5-anhydro-d-glucitol (1,5-AG), and renal factors including plasma urea
      nitrogen and creatinine levels, urine volume, glucose, and albumin were examined
      once a week for 9 weeks in diabetic mice with or without transplantation of
      encapsulated rat islets, and in normal C57BL/6 mice. The mesangial matrix
      fraction of the glomerulus was measured histologically. The mice were classified
      into 3 groups according to their mean plasma glucose levels as either severe (n =
      17) or mild (n = 23) hyperglycemia or normoglycemia (n = 11). The plasma glucose,
      renal factors, and mesangial matrix fraction were tested by single and multiple
      regression analyses. RESULTS: Almost all the renal factors correlated
      significantly with mean plasma glucose and 1,5-AG levels. The level and duration
      of hyperglycemia estimated by the area under the curve above basal correlated
      most significantly with mesangial matrix fraction. CONCLUSIONS: Bioartificial
      pancreas transplantation significantly reduced the deterioration of renal
      factors. The 1,5-AG was useful to predict urine albumin loss. The level and
      duration of hyperglycemia determined the degree of renal damage, which were
      reduced by bioartificial pancreas transplantation.

PMID- 17446847
TI  - The level of carcinoembryonic antigen and the presence of mucin as predictors of
      cystic pancreatic mucinous neoplasia.
AB  - OBJECTIVES: Characterization of pancreatic cysts using endoscopic ultrasound
      guided fine-needle aspiration includes cytological interpretation and chemical
      analysis. We prospectively analyzed the contribution of carcinoembryonic antigen
      (CEA) and cytological identification of extracellular mucin as predictors of
      mucinous neoplasia and malignancy. METHODS: From January 2003 to October 2005,
      all patients referred to the University of Virginia with cystic lesions of the
      pancreas underwent endoscopic ultrasound-guided fine-needle aspiration with
      cytological evaluation and CEA level analysis. Data were collected prospectively
      and confirmed by resection or tissue biopsy. Univariate and multivariate analyses
      were performed on the following variables with regard to their ability to predict
      mucinous neoplasia: age (<55 or >55 years), sex, CEA level (<300 or >300 ng/mL),
      and cytological appreciation of extracellular mucin (positive or negative). P
      values less than 0.05 were considered significant. RESULTS: A total of 43
      patients were included in this study. There were 19 men and 24 women with a mean
      age of 63 +/- 14 years. The only complication was pancreatitis secondary to cyst
      leak in one patient. Multivariate analysis confirmed CEA level greater than 300
      ng/mL (P= 0.007) and the identification of mucin (P < 0.001) as significant
      predictors. CONCLUSIONS: With pancreatic cyst fluid analysis, the strongest
      predictor of mucinous neoplasia is the presence of identifiable mucin, followed
      by a CEA level greater than 300 ng/mL. The workup of cystic lesions of the
      pancreas should include chemical analysis for the CEA level and cytological
      examination with particular attention to extracellular mucin.

PMID- 17446848
TI  - Mucinous cystadenocarcinoma of the pancreas during pregnancy.
AB  - The occurrence of a mucinous cystadenocarcinoma of the pancreas during pregnancy
      is extremely rare, reported in only twice in the English literature. We describe
      a 34-year-old patient with this rare condition who was successfully managed by
      resection of the tumor with distal pancreatectomy and splenectomy. The operation
      was performed at 15 weeks of gestation, and the patient went on to deliver a
      healthy infant at 39 weeks. To our knowledge, this is the first report of
      successful resection of a cystadenocarcinoma of the pancreas during pregnancy.
      The specimen weighed 2500 g and measured 20 cm across, making it the largest
      reported mucinous cystadenocarcinoma of the pancreas encountered during pregnancy
      to date.

PMID- 17446849
TI  - An extremely rare cause of acute abdomen in pregnancy: ruptured pancreatic
      mucinous cystadenocarcinoma.
AB  - Pancreatic cystadenocarcinoma is an extremely rare neoplasm in pregnancy. To our
      knowledge, there have been 2 published cases of pancreatic mucinous
      cystadenocarcinoma (PMC) during pregnancy in the literature; one of which was
      reported to have ruptured into the abdominal cavity. We present a second case of
      ruptured PMC resulting in acute abdomen in 36 weeks of pregnancy. Rupture of
      mucinous cystic neoplasms of pancreas including PMC should be remembered in acute
      abdomen during pregnancy.

PMID- 17446850
TI  - Rupture of infected peripancreatic necrosis to the peritoneal cavity with fatal
      outcome.

PMID- 17446851
TI  - Allochronic biliary strictures appeared in the different regions of the bile duct
      tree in a patient with autoimmune pancreatitis.

PMID- 17446852
TI  - Intraductal papillary mucinous neoplasm with invasive carcinoma in the setting of
      chronic alcoholic pancreatitis.

PMID- 17446853
TI  - The extended local resection for the lesion of the vater papilla
      papillosphincterectomy.

PMID- 17446854
TI  - Acute pancreatitis associated with the use of peginterferon.

PMID- 17446855
TI  - Increase of high-mobility group box chromosomal protein 1 in blood and injured
      organs in experimental severe acute pancreatitis.

PMID- 17446856
TI  - Heterotopic pancreas in the gallbladder: the importance of an uncommon condition.

PMID- 17446857
TI  - Triterpenoids and rexinoids as multifunctional agents for the prevention and
      treatment of cancer.
AB  - Synthetic oleanane triterpenoids and rexinoids are two new classes of
      multifunctional drugs. They are neither conventional cytotoxic agents, nor are
      they monofunctional drugs that uniquely target single steps in signal
      transduction pathways. Synthetic oleanane triterpenoids have profound effects on
      inflammation and the redox state of cells and tissues, as well as being potent
      anti-proliferative and pro-apoptotic agents. Rexinoids are ligands for the
      nuclear receptor transcription factors known as retinoid X receptors. Both
      classes of agents can prevent and treat cancer in experimental animals. These
      drugs have unique molecular and cellular mechanisms of action and might prove to
      be synergistic with standard anti-cancer treatments.

PMID- 17446858
TI  - Insights from transgenic mouse models of ERBB2-induced breast cancer.
AB  - One-third of patients with breast cancer overexpress the ERBB2 receptor tyrosine
      kinase, which is associated not only with a more aggressive phenotype but also
      reduced responsiveness to hormonal therapies. Over the past two decades, many
      ERBB2 mouse models for breast cancer have conclusively shown that this receptor
      has a causal role in breast cancer development. These mouse models have also
      enabled the mechanisms controlling tumour growth, angiogenesis, metastasis,
      dormancy and recurrence in ERBB2-positive breast cancer to be elucidated. In
      addition, a mouse model has recently been described that accurately recapitulates
      many of the hallmarks associated with the early stages of the human disease.

PMID- 17446859
TI  - Sulfatase modifying factor 1 trafficking through the cells: from endoplasmic
      reticulum to the endoplasmic reticulum.
AB  - Sulfatase modifying factor 1 (SUMF1) is the gene mutated in multiple sulfatase
      deficiency (MSD) that encodes the formylglycine-generating enzyme, an essential
      activator of all the sulfatases. SUMF1 is a glycosylated enzyme that is resident
      in the endoplasmic reticulum (ER), although it is also secreted. Here, we
      demonstrate that upon secretion, SUMF1 can be taken up from the medium by several
      cell lines. Furthermore, the in vivo engineering of mice liver to produce SUMF1
      shows its secretion into the blood serum and its uptake into different tissues.
      Additionally, we show that non-glycosylated forms of SUMF1 can still be secreted,
      while only the glycosylated SUMF1 enters cells, via a receptor-mediated
      mechanism. Surprisingly, following its uptake, SUMF1 shuttles from the plasma
      membrane to the ER, a route that has to date only been well characterized for
      some of the toxins. Remarkably, once taken up and relocalized into the ER, SUMF1
      is still active, enhancing the sulfatase activities in both cultured cells and
      mice tissues.

PMID- 17446860
TI  - Dual mechanisms specify Doa4-mediated deubiquitination at multivesicular bodies.
AB  - Doa4 is a ubiquitin-specific protease in Saccharomyces cerevisiae that
      deubiquitinates integral membrane proteins sorted into the lumenal vesicles of
      late-endosomal multivesicular bodies (MVBs). We show that the non-catalytic N
      terminus of Doa4 mediates its recruitment to endosomes through its association
      with Bro1, which is one of several highly conserved class E Vps proteins that
      comprise the core MVB sorting machinery. In turn, Bro1 directly stimulates
      deubiquitination by interacting with a YPxL motif in the catalytic domain of
      Doa4. Mutations in either Doa4 or Bro1 that disrupt catalytic activation of Doa4
      impair deubiquitination and sorting of MVB cargo proteins and lead to the
      formation of lumenal MVB vesicles that are predominantly small compared with the
      vesicles seen in wild-type cells. Thus, by recruiting Doa4 to late endosomes and
      stimulating its catalytic activity, Bro1 fulfills a novel dual role in
      coordinating deubiquitination in the MVB pathway.

PMID- 17446861
TI  - Specific functions for the fission yeast Sirtuins Hst2 and Hst4 in gene
      regulation and retrotransposon silencing.
AB  - Expression profiling, ChiP-CHIP and phenotypic analysis were used to investigate
      the functional relationships of class III NAD(+)-dependent HDACs (Sirtuins) in
      fission yeast. We detected significant histone acetylation increases in Sirtuin
      mutants at their specific genomic binding targets and were thus able to identify
      an in vivo substrate preference for each Sirtuin. At heterochromatic loci, we
      demonstrate that although Hst2 is mainly cytoplasmic, a nuclear pool of Hst2
      colocalizes with the other Sirtuins at silent regions (cen, mat, tel, rDNA), and
      that like the other Sirtuins, Hst2 is required for rDNA and centromeric
      silencing. Interestingly we found specific functions for the fission yeast
      Sirtuins Hst2 and Hst4 in gene regulation. Hst2 directly represses genes involved
      in transport and membrane function, whereas Hst4 represses amino-acid
      biosynthesis genes and Tf2 retrotransposons. A specific role for Hst4 in Tf2 5'
      mRNA processing was revealed. Thus, Sirtuins share functions at many genomic
      targets, but Hst2 and Hst4 have also evolved unique functions in gene regulation.

PMID- 17446862
TI  - Functional and physical interaction between Bcl-X(L) and a BH3-like domain in
      Beclin-1.
AB  - The anti-apoptotic proteins Bcl-2 and Bcl-X(L) bind and inhibit Beclin-1, an
      essential mediator of autophagy. Here, we demonstrate that this interaction
      involves a BH3 domain within Beclin-1 (residues 114-123). The physical
      interaction between Beclin-1 and Bcl-X(L) is lost when the BH3 domain of Beclin-1
      or the BH3 receptor domain of Bcl-X(L) is mutated. Mutation of the BH3 domain of
      Beclin-1 or of the BH3 receptor domain of Bcl-X(L) abolishes the Bcl-X(L)
      mediated inhibition of autophagy triggered by Beclin-1. The pharmacological BH3
      mimetic ABT737 competitively inhibits the interaction between Beclin-1 and Bcl
      2/Bcl-X(L), antagonizes autophagy inhibition by Bcl-2/Bcl-X(L) and hence
      stimulates autophagy. Knockout or knockdown of the BH3-only protein Bad reduces
      starvation-induced autophagy, whereas Bad overexpression induces autophagy in
      human cells. Gain-of-function mutation of the sole BH3-only protein from
      Caenorhabditis elegans, EGL-1, induces autophagy, while deletion of EGL-1
      compromises starvation-induced autophagy. These results reveal a novel autophagy
      stimulatory function of BH3-only proteins beyond their established role as
      apoptosis inducers. BH3-only proteins and pharmacological BH3 mimetics induce
      autophagy by competitively disrupting the interaction between Beclin-1 and Bcl-2
      or Bcl-X(L).

PMID- 17446863
TI  - Anthrax lethal toxin paralyzes actin-based motility by blocking Hsp27
      phosphorylation.
AB  - Inhalation of anthrax causes fatal bacteremia, indicating a meager host immune
      response. We previously showed that anthrax lethal toxin (LT) paralyzes
      neutrophils, a major component of innate immunity. Here, we have found that LT
      also inhibits actin-based motility of the intracellular pathogen Listeria
      monocytogenes. LT inhibition of actin assembly is mediated by blockade of Hsp27
      phosphorylation, and can be reproduced by treating cells with the p38 mitogen
      activated protein (MAP) kinase inhibitor SB203580. Nonphosphorylated Hsp27
      inhibits Listeria actin-based motility in cell extracts, and binds to and
      sequesters purified actin monomers. Phosphorylation of Hsp27 reverses these
      effects. RNA interference knockdown of Hsp27 blocks LT inhibition of Listeria
      actin-based motility. Rescue with wild-type Hsp27 accelerates Listeria speed in
      knockdown cells, whereas introduction of Hsp27 mutants incapable of
      phosphorylation or dephosphorylation causes slowing down. We propose that Hsp27
      facilitates actin-based motility through a phosphorylation cycle that shuttles
      actin monomers to regions of new actin filament assembly. Our findings provide a
      previously unappreciated mechanism for LT virulence, and emphasize a central role
      for p38 MAP kinase-mediated phosphorylation of Hsp27 in actin-based motility and
      innate immunity.

PMID- 17446864
TI  - Proteomic screen defines the Polo-box domain interactome and identifies Rock2 as
      a Plk1 substrate.
AB  - Polo-like kinase-1 (Plk1) phosphorylates a number of mitotic substrates, but the
      diversity of Plk1-dependent processes suggests the existence of additional
      targets. Plk1 contains a specialized phosphoserine-threonine binding domain, the
      Polo-box domain (PBD), postulated to target the kinase to its substrates. Using
      the specialized PBD of Plk1 as an affinity capture agent, we performed a screen
      to define the mitotic Plk1-PBD interactome by mass spectrometry. We identified
      622 proteins that showed phosphorylation-dependent mitosis-specific interactions,
      including proteins involved in well-established Plk1-regulated processes, and in
      processes not previously linked to Plk1 such as translational control, RNA
      processing, and vesicle transport. Many proteins identified in our screen play
      important roles in cytokinesis, where, in mammalian cells, the detailed
      mechanistic role of Plk1 remains poorly defined. We go on to characterize the
      mitosis-specific interaction of the Plk1-PBD with the cytokinesis effector kinase
      Rho-associated coiled-coil domain-containing protein kinase 2 (Rock2),
      demonstrate that Rock2 is a Plk1 substrate, and show that Rock2 colocalizes with
      Plk1 during cytokinesis. Finally, we show that Plk1 and RhoA function together to
      maximally enhance Rock2 kinase activity in vitro and within cells, and implicate
      Plk1 as a central regulator of multiple pathways that synergistically converge to
      regulate actomyosin ring contraction during cleavage furrow ingression.

PMID- 17446865
TI  - Mechanism for activation of the growth factor-activated AGC kinases by turn motif
      phosphorylation.
AB  - The growth factor/insulin-stimulated AGC kinases share an activation mechanism
      based on three phosphorylation sites. Of these, only the role of the activation
      loop phosphate in the kinase domain and the hydrophobic motif (HM) phosphate in a
      C-terminal tail region are well characterized. We investigated the role of the
      third, so-called turn motif phosphate, also located in the tail, in the AGC
      kinases PKB, S6K, RSK, MSK, PRK and PKC. We report cooperative action of the HM
      phosphate and the turn motif phosphate, because it binds a phosphoSer/Thr-binding
      site above the glycine-rich loop within the kinase domain, promoting zipper-like
      association of the tail with the kinase domain, serving to stabilize the HM in
      its kinase-activating binding site. We present a molecular model for allosteric
      activation of AGC kinases by the turn motif phosphate via HM-mediated
      stabilization of the alphaC helix. In S6K and MSK, the turn motif phosphate
      thereby also protects the HM from dephosphorylation. Our results suggest that the
      mechanism described is a key feature in activation of upto 26 human AGC kinases.

PMID- 17446866
TI  - Translation of nonSTOP mRNA is repressed post-initiation in mammalian cells.
AB  - We investigated the fate of aberrant mRNAs lacking in-frame termination codons
      (called nonSTOP mRNA) in mammalian cells. We found that translation of nonSTOP
      mRNA was considerably repressed although a corresponding reduction of mRNA was
      not observed. The repression appears to be post-initiation since (i) repressed
      nonSTOP mRNAs were associated with polysomes, (ii) translation of IRES-initiated
      and uncapped nonSTOP mRNA were repressed, and (iii) protein production from
      nonSTOP mRNA associating with polysomes was significantly reduced when used to
      program an in vitro run-off translation assay. NonSTOP mRNAs distributed into
      lighter polysome fractions compared to control mRNAs encoding a stop codon, and a
      significant amount of heterogeneous polypeptides were produced during in vitro
      translation of nonSTOP RNAs, suggesting premature termination of ribosomes
      translating nonSTOP mRNA. Moreover, a run-off translation assay using
      hippuristanol and RNAse protection assays suggested the presence of a ribosome
      stalled at the 3' end of nonSTOP mRNAs. Taken together, these data indicate that
      ribosome stalling at the 3' end of nonSTOP mRNAs can block translation by
      preventing upstream translation events.

PMID- 17446868
TI  - Shedding light on tumor targeting by adenovirus.

PMID- 17446867
TI  - Structures of modified eEF2 80S ribosome complexes reveal the role of GTP
      hydrolysis in translocation.
AB  - On the basis of kinetic data on ribosome protein synthesis, the mechanical energy
      for translocation of the mRNA-tRNA complex is thought to be provided by GTP
      hydrolysis of an elongation factor (eEF2 in eukaryotes, EF-G in bacteria). We
      have obtained cryo-EM reconstructions of eukaryotic ribosomes complexed with ADP
      ribosylated eEF2 (ADPR-eEF2), before and after GTP hydrolysis, providing a
      structural basis for analyzing the GTPase-coupled mechanism of translocation.
      Using the ADP-ribosyl group as a distinct marker, we observe conformational
      changes of ADPR-eEF2 that are due strictly to GTP hydrolysis. These movements are
      likely representative of native eEF2 motions in a physiological context and are
      sufficient to uncouple the mRNA-tRNA complex from two universally conserved bases
      in the ribosomal decoding center (A1492 and A1493 in Escherichia coli) during
      translocation. Interpretation of these data provides a detailed two-step model of
      translocation that begins with the eEF2/EF-G binding-induced ratcheting motion of
      the small ribosomal subunit. GTP hydrolysis then uncouples the mRNA-tRNA complex
      from the decoding center so translocation of the mRNA-tRNA moiety may be
      completed by a head rotation of the small subunit.

PMID- 17446872
TI  - I could die for you: new prospects for suicide in gene therapy.

PMID- 17446871
TI  - Programming the next generation of dendritic cells.

PMID- 17446873
TI  - Total internal reflection with fluorescence correlation spectroscopy.
AB  - Total internal reflection-fluorescence correlation spectroscopy (TIR-FCS) is an
      emerging technique that is used to measure events at or near an interface,
      including local fluorophore concentrations, local translational mobilities and
      the kinetic rate constants that describe the association and dissociation of
      fluorophores at the interface. TIR-FCS is also an extremely promising method for
      studying dynamics at or near the basal membranes of living cells. This protocol
      gives a general overview of the steps necessary to construct and test a TIR-FCS
      system using either through-prism or through-objective internal reflection
      geometry adapted for FCS. The expected forms of the autocorrelation function are
      discussed for the cases in which fluorescent molecules in solution diffuse
      through the depth of the evanescent field, but do not bind to the surface of
      interest, and in which reversible binding to the surface also occurs.

PMID- 17446874
TI  - Gene splicing and mutagenesis by PCR-driven overlap extension.
AB  - Extension of overlapping gene segments by PCR is a simple, versatile technique
      for site-directed mutagenesis and gene splicing. Initial PCRs generate
      overlapping gene segments that are then used as template DNA for another PCR to
      create a full-length product. Internal primers generate overlapping,
      complementary 3' ends on the intermediate segments and introduce nucleotide
      substitutions, insertions or deletions for site-directed mutagenesis, or for gene
      splicing, encode the nucleotides found at the junction of adjoining gene
      segments. Overlapping strands of these intermediate products hybridize at this 3'
      region in a subsequent PCR and are extended to generate the full-length product
      amplified by flanking primers that can include restriction enzyme sites for
      inserting the product into an expression vector for cloning purposes. The highly
      efficient generation of mutant or chimeric genes by this method can easily be
      accomplished with standard laboratory reagents in approximately 1 week.

PMID- 17446875
TI  - Synthesis, purification and sample experiment for fluorescent pteridine
      containing DNA: tools for studying DNA interactive systems.
AB  - Fluorescent nucleoside analogs provide a means to study DNA interactive systems
      through direct measurement of fluorescence properties. As integrated parts of
      DNA, these probes provide opportunities for monitoring subtle changes in DNA
      structure as it meets and reacts with other molecules. This protocol describes
      modifications to standard DNA synthesis to efficiently use smaller volumes of the
      probe phosphoramidite, purification of pteridine-containing sequences and a
      deprotection procedure specific for 6MI-containing sequences. Yields for probe
      incorporation in DNA synthesis are comparable to those for standard
      phosphoramidites. Examples of the fluorescence signals one can expect are
      described. Automated synthesis, which is dependent on the length of the sequence,
      takes about 4-5 h for a 20-mer. The deprotection of 6MI-containing sequences
      takes approximately 6-7 h before the standard ammonium hydroxide overnight
      incubation. Purification through polyacrylamide gels, electroelution and ethanol
      precipitation can be accomplished in 6-8 h.

PMID- 17446876
TI  - Identification of host-induced pathogen genes by differential fluorescence
      induction reporter systems.
AB  - The ability to monitor a pathogen's gene expression program in response to the
      host environment is central to understanding host-microbe interactions. This
      protocol describes the application of a fluorescence-based promoter trap
      strategy, termed differential fluorescence induction (DFI), to identify and
      characterize bacterial genes that are preferentially expressed in infected
      tissues. In this approach, animals are infected with a library of bacteria
      expressing random GFP transcriptional gene fusions, and fluorescent bacteria are
      recovered directly from host tissues using fluorescence-activated cell sorting
      (FACS). This methodology allows for the identification of bacterial promoters
      induced in distinct anatomical sites and at different stages of infection.
      Furthermore, unlike other methodologies, the use of the GFP reporter allows for
      single cell, temporal and spatial monitoring of pathogen gene expression in
      infected animals. Library construction, promoter identification and analysis can
      be done in 4-8 weeks.

PMID- 17446877
TI  - Untargeted large-scale plant metabolomics using liquid chromatography coupled to
      mass spectrometry.
AB  - Untargeted metabolomics aims to gather information on as many metabolites as
      possible in biological systems by taking into account all information present in
      the data sets. Here we describe a detailed protocol for large-scale untargeted
      metabolomics of plant tissues, based on reversed phase liquid chromatography
      coupled to high-resolution mass spectrometry (LC-QTOF MS) of aqueous methanol
      extracts. Dedicated software, MetAlign, is used for automated baseline correction
      and alignment of all extracted mass peaks across all samples, producing detailed
      information on the relative abundance of thousands of mass signals representing
      hundreds of metabolites. Subsequent statistics and bioinformatics tools can be
      used to provide a detailed view on the differences and similarities between
      (groups of) samples or to link metabolomics data to other systems biology
      information, genetic markers and/or specific quality parameters. The complete
      procedure from metabolite extraction to assembly of a data matrix with aligned
      mass signal intensities takes about 6 days for 50 samples.

PMID- 17446878
TI  - A method for genetic modification of human embryonic stem cells using
      electroporation.
AB  - The ability to genetically modify human embryonic stem cells (HESCs) will be
      critical for their widespread use as a tool for understanding fundamental aspects
      of human biology and pathology and for their development as a platform for
      pharmaceutical discovery. Here, we describe a method for the genetic modification
      of HESCs using electroporation, the preferred method for introduction of DNA into
      cells in which the desired outcome is gene targeting. This report provides
      methods for cell amplification, electroporation, colony selection and screening.
      The protocol we describe has been tested on four different HESC lines, and takes
      approximately 4 weeks from electroporation to PCR screening of G418-resistant
      clones.

PMID- 17446879
TI  - In vivo imaging of subcutaneous structures using functional photoacoustic
      microscopy.
AB  - Functional photoacoustic microscopy (fPAM) is a hybrid technology that permits
      noninvasive imaging of the optical absorption contrast in subcutaneous biological
      tissues. fPAM uses a focused ultrasonic transducer to detect high-frequency
      photoacoustic (PA) signals. Volumetric images of biological tissues can be formed
      by two-dimensional raster scanning, and functional parameters can be further
      extracted from spectral measurements. fPAM is safe and applicable to animals as
      well as humans. This protocol provides guidelines for parameter selection, system
      alignment, imaging operation, laser safety and data processing for in vivo fPAM.
      It currently takes approximately 100 min to carry out this protocol, including
      approximately 50 min for data acquisition using a 10-Hz pulse-repetition-rate
      laser system. The data acquisition time, however, can be significantly reduced by
      using a laser system with a higher pulse repetition rate.

PMID- 17446880
TI  - A protocol for phenotypic detection and enumeration of circulating endothelial
      cells and circulating progenitor cells in human blood.
AB  - Blood circulating endothelial cells (CECs) and circulating hematopoietic
      progenitor cells (CPCs) represent two cell populations that are thought to play
      important roles in tissue vascularization. CECs and CPCs are currently studied as
      surrogate markers in patients for more than a dozen pathologies, including heart
      disease and cancer. However, data interpretation has often been difficult because
      of multiple definitions, methods and protocols used to evaluate and count these
      cells by different laboratories. Here, we propose a cytometry protocol for
      phenotypic identification and enumeration of CECs and CPCs in human blood using
      four surface markers: CD31, CD34, CD133 and CD45. This method allows further
      phenotypic analyses to explore the biology of these cells. In addition, it offers
      a platform for longitudinal studies of these cells in patients with different
      pathologies. The protocol is relatively simple, inexpensive and can be adapted
      for multiple flow cytometer types or software. The procedure should take 2-2.5 h,
      and is expected to detect 0.1-6.0% viable CECs and 0.01-0.20% CPCs within blood
      mononuclear cell population.

PMID- 17446881
TI  - Genetic manipulation of Aspergillus nidulans: meiotic progeny for genetic
      analysis and strain construction.
AB  - The multicellular microbial eukaryote Aspergillus nidulans is an excellent model
      for the study of a wide array of biological processes. Studies in this system
      contribute significantly to understanding fundamental biological principles and
      are relevant for biotechnology and industrial applications, as well as human,
      animal and plant fungal pathogenesis. A. nidulans is easily manipulated using
      classical and molecular genetics. Here, we describe the storage and handling of
      A. nidulans and procedures for genetic crossing, progeny analysis and growth
      testing. These procedures are used for Mendelian analysis of segregation of
      alleles to show whether a mutant phenotype segregates as a single gene and
      independent assortment of genes to determine the linkage relationship between
      genes. Meiotic crossing is used for construction of multiple mutant strains for
      genetic analysis. Genetic crossing and analysis of progeny can be undertaken in 2
      3 weeks and growth testing takes 2-3 days.

PMID- 17446882
TI  - Genetic manipulation of Aspergillus nidulans: heterokaryons and diploids for
      dominance, complementation and haploidization analyses.
AB  - The haploid microbial eukaryote Aspergillus nidulans is a powerful genetic
      system, which allows analysis of a broad range of biological phenomena. In
      addition to conventional analysis of meiotic progeny in a single generation,
      parasexual analysis affords a rapid and convenient method for genetic analysis.
      We describe the construction of A. nidulans heterokaryons and diploids for use in
      genetic analysis to determine dominance and conduct complementation tests. We
      also describe the rapid mapping of mutations to chromosomes by haploidization of
      diploids carrying marked chromosomes. Balanced heterokaryons may be established
      within 10 days and diploids may be constructed in 2-3 weeks. Dominance tests and
      complementation tests using balanced heterokaryons or diploids may be completed
      in 2-3 days. Haploidization analysis of heterozygous diploids can be achieved
      within 10 days. These protocols should be adaptable for use in related Aspergilli
      and Penicillia, which lack a known meiotic cycle.

PMID- 17446883
TI  - Protocol for the purification of proteins from biological extracts for
      identification by mass spectrometry.
AB  - When a protein signal is selected by mass spectrometry as being a potential
      biomarker, it is necessary to formally identify it. This process involves
      separation of the protein in question and its identification by either peptide
      fingerprinting or tandem mass spectrometry sequencing. In the following pages, a
      simple and rapid protocol is described. Basically, the protocol consists of an
      initial rational selection of a few sorbents followed by alignment of these as a
      series of columns to obtain the purified target protein. This preparation is then
      submitted to electrophoresis, the band is excised and the trypsin digest is
      analyzed by either mass spectrometry (mass fingerprinting approach) or by LC
      MS/MS (sequencing). The development of the process takes only a few days.
      Experimental data for the isolation and identification of proteins are discussed
      and two examples are shown.

PMID- 17446884
TI  - RNA stable-isotope probing.
AB  - At the heart of microbial ecology lies a true scientific dichotomy. On the one
      hand, we know microbes are responsible for processes on which all other life on
      Earth is dependent; their removal would mean the cessation of all known life.
      However, in opposition, the majority of extant microbial species in natural
      environments have never been cultured or studied in a laboratory as living
      organisms. Owing to these factors, the question of "who does what?" has been a
      major barrier to understanding how microbially mediated ecosystem level events
      occur. Recently, the use of stable isotopes (13C) to trace carbon from specific
      substrates into microbes that assimilate carbon from that substrate has
      significantly advanced our understanding of the relationship between
      environmental processes and microbial phylogeny.

PMID- 17446885
TI  - Practical and convenient synthesis of coumarins from phenols and propiolic acid
      esters.
AB  - This protocol describes the synthesis of 6,7-methylenedioxy-4-phenylcoumarin from
      sesamol and ethyl phenylpropiolate using a Pd(OAc)2 catalyst to illustrate
      coumarin synthesis. This procedure is simple and easy and can be applied to the
      synthesis of other coumarins that have electron-rich phenol groups. The reaction
      is conducted by stirring a solution of Pd(OAc)2, sesamol and ethyl
      phenylpropiolate in trifluoroacetic acid at room temperature (15-20 degrees C)
      under atmospheric conditions. This protocol can be completed in 3 d.

PMID- 17446886
TI  - DNA stable-isotope probing.
AB  - Stable-isotope probing is a method used in microbial ecology that provides a
      means by which specific functional groups of organisms that incorporate
      particular substrates are identified without the prerequisite of cultivation.
      Stable-isotope-labeled carbon (13C) or nitrogen (15N) sources are assimilated
      into microbial biomass of environmental samples. Separation and molecular
      analysis of labeled nucleic acids (DNA or RNA) reveals phylogenetic and
      functional information about the microorganisms responsible for the metabolism of
      a particular substrate. Here, we highlight general guidelines for incubating
      environmental samples with labeled substrate and provide a detailed protocol for
      separating labeled DNA from unlabeled community DNA. The protocol includes a
      modification of existing published methods, which maximizes the recovery of
      labeled DNA from CsCl gradients. The separation of DNA and retrieval of unlabeled
      and labeled fractions can be performed in 4-5 days, with much of the time being
      committed to the ultracentrifugation step.

PMID- 17446887
TI  - Rapid measurement of total antioxidant capacity in plants.
AB  - There is growing interest in measuring the antioxidant status of plant tissues.
      This protocol describes the oxygen radical absorbance capacity (ORAC) assay,
      which measures antioxidant inhibition of peroxyl radical-induced oxidations and
      is a measure of total antioxidant capacity. The assay is performed in a
      microplate and is assessed with a 96-well multi-detection plate reader. Total
      antioxidant capacity of 64 experimental samples can easily be analyzed in 1 d.
      This assay is presented along with rapid assays for total phenolic content and
      total ascorbate content. Overall, these assays provide a general diagnostic tool
      of the antioxidant capacity in leaf tissue extracts.

PMID- 17446888
TI  - Measurement of reduced, oxidized and total ascorbate content in plants.
AB  - Ascorbate is one of the major antioxidant metabolites in plant tissues. This
      protocol describes a microplate-adapted colorimetric ascorbate assay, in which
      ferric ion is reduced by ascorbate to the ferrous ion. The ferrous ion reacts
      with alpha-alpha'-bipyridl to form a complex with characteristic absorbance at
      525 nm. With the chemical reduction of any dehydroascorbate (DHA) in a sample,
      total ascorbate can be assayed using the alpha-alpha'-bipyridl method, and DHA
      can be estimated by subtracting the reduced portion from the total ascorbate
      pool. The assay is performed in microcentrifuge tubes and assessed in a 96-well
      plate reader. Reduced ascorbate, DHA and total ascorbate of at least 64
      experimental samples can be analyzed easily in 1 d.

PMID- 17446889
TI  - Estimation of total phenolic content and other oxidation substrates in plant
      tissues using Folin-Ciocalteu reagent.
AB  - Non-structural phenolic compounds perform a variety of functions in plants,
      including acting as antioxidants. We describe a microplate-adapted colorimetric
      total phenolics assay that utilizes Folin-Ciocalteu (F-C) reagent. The F-C assay
      relies on the transfer of electrons in alkaline medium from phenolic compounds to
      phosphomolybdic/phosphotungstic acid complexes, which are determined
      spectroscopically at 765 nm. Although the electron transfer reaction is not
      specific for phenolic compounds, the extraction procedure eliminates
      approximately 85% of ascorbic acid and other potentially interfering compounds.
      This assay is performed in microcentrifuge tubes and assessed in a 96-well plate
      reader. At least 64 samples can be processed in 1 d.

PMID- 17446890
TI  - Iterative saturation mutagenesis (ISM) for rapid directed evolution of functional
      enzymes.
AB  - Iterative saturation mutagenesis (ISM) is a new and efficient method for the
      directed evolution of functional enzymes. It reduces the necessary molecular
      biological work and the screening effort drastically. It is based on a Cartesian
      view of the protein structure, performing iterative cycles of saturation
      mutagenesis at rationally chosen sites in an enzyme, a given site being composed
      of one, two or three amino acid positions. The basis for choosing these sites
      depends on the nature of the catalytic property to be improved, e.g.,
      enantioselectivity, substrate acceptance or thermostability. In the case of
      thermostability, sites showing highest B-factors (available from X-ray data) are
      chosen. The pronounced increase in thermostability of the lipase from Bacillus
      subtilis (Lip A) as a result of applying ISM is illustrated here.

PMID- 17446891
TI  - Spin labeling of oligonucleotides with the nitroxide TPA and use of PELDOR, a
      pulse EPR method, to measure intramolecular distances.
AB  - In this protocol, we describe the facile synthesis of the nitroxide spin-label
      2,2,5,5-tetramethyl-pyrrolin-1-oxyl-3-acetylene (TPA) and then its coupling to
      DNA/RNA through Sonogashira cross-coupling during automated solid-phase
      synthesis. Subsequently, we explain how to perform distance measurements between
      two such spin-labels on RNA/DNA using the pulsed electron paramagnetic resonance
      method pulsed electron double resonance (PELDOR). This combination of methods can
      be used to study global structure elements of oligonucleotides in frozen solution
      at RNA/DNA amounts of approximately 10 nmol. We especially focus on the
      Sonogashira cross-coupling step, the advantages of the ACE chemistry together
      with the appropriate parameters for the RNA synthesizer and on the PELDOR data
      analysis. This procedure is applicable to RNA/DNA strands of up to approximately
      80 bases in length and PELDOR yields reliably spin-spin distances up to
      approximately 6.5 nm. The synthesis of TPA takes approximately 5 days and spin
      labeling together with purification approximately 4 days. The PELDOR measurements
      usually take approximately 16 h and data analysis from an hour up to several days
      depending on the extent of analysis.

PMID- 17446892
TI  - Chemical derivatization of histones for facilitated analysis by mass
      spectrometry.
AB  - Histone post-translational modifications have been recently intensely studied
      owing to their role in regulating gene expression. Here, we describe protocols
      for the characterization of histone modifications in both qualitative and
      semiquantitative manners using chemical derivatization and tandem mass
      spectrometry. In these procedures, extracted histones are first derivatized using
      propionic anhydride to neutralize charge and block lysine residues, and are
      subsequently digested using trypsin, which, under these conditions, cleaves only
      the arginine residues. The generated peptides can be easily analyzed using online
      LC-electrospray ionization-tandem mass spectrometry to identify the modification
      site. In addition, a stable isotope-labeling step can be included to modify
      carboxylic acid groups allowing for relative quantification of histone
      modifications. This methodology has the advantage of producing a small number of
      predicted peptides from highly modified proteins. The protocol should take
      approximately 15-19 h to complete, including all chemical reactions, enzymatic
      digestion and mass spectrometry experiments.

PMID- 17446893
TI  - Preparation of cultured myofibers from larval salamander limbs for cellular
      plasticity studies.
AB  - Identification of the mechanisms underlying cellular plasticity in salamander
      cells is important because these may give pointers to the restricted regenerative
      ability of mammals. The myofibers from salamanders are remarkable for their
      ability to undergo cellularization and cell-cycle re-entry during regeneration.
      Here, we describe a detailed method for the isolation and culture of larval
      salamander myofibers in numbers suitable for cellular plasticity studies. The
      basic protocol for isolation and purification of cells can be completed in 4 h.

PMID- 17446894
TI  - Agrobacterium rhizogenes-mediated transformation of soybean to study root
      biology.
AB  - This protocol is used to induce transgenic roots on soybean to study the function
      of genes required in biological processes of the root. Young seedlings with
      unfolded cotyledons are infected at the cotyledonary node and/or hypocotyl with
      Agrobacterium rhizogenes carrying the gene construct to be tested and the
      infection sites are kept in an environment of high humidity. When the emerged
      hairy roots can support the plants, the main roots are removed and the transgenic
      roots can be tested. Using this method, almost 100% of the infected plants form
      hairy roots within 1 month from the start of the experiments.

PMID- 17446895
TI  - Locating proteins in the cell using TargetP, SignalP and related tools.
AB  - Determining the subcellular localization of a protein is an important first step
      toward understanding its function. Here, we describe the properties of three well
      known N-terminal sequence motifs directing proteins to the secretory pathway,
      mitochondria and chloroplasts, and sketch a brief history of methods to predict
      subcellular localization based on these sorting signals and other sequence
      properties. We then outline how to use a number of internet-accessible tools to
      arrive at a reliable subcellular localization prediction for eukaryotic and
      prokaryotic proteins. In particular, we provide detailed step-by-step
      instructions for the coupled use of the amino-acid sequence-based predictors
      TargetP, SignalP, ChloroP and TMHMM, which are all hosted at the Center for
      Biological Sequence Analysis, Technical University of Denmark. In addition, we
      describe and provide web references to other useful subcellular localization
      predictors. Finally, we discuss predictive performance measures in general and
      the performance of TargetP and SignalP in particular.

PMID- 17446896
TI  - An improved synthesis of NHS-MAG3 for conjugation and radiolabeling of
      biomolecules with (99m)Tc at room temperature.
AB  - The mercaptoacetyltriglycine (MAG3) chelator has been shown to stably complex
      technetium-99m (99mTc) for nuclear imaging and radiorhenium (186/188Re) for tumor
      radiation therapy studies. The bifunctional N-hydroxysuccinimidyl ester of MAG3
      with S-acetyl protection (N-hydroxysuccinimidyl S
      acetylmercaptoacetyltriglycinate (NHS-MAG3)) has been successfully used to
      covalently conjugate a MAG3 chelator to primary amine functionalized
      biomolecules. We describe herein a simplified synthesis of NHS-MAG3 that begins
      with the preparation of the N-hydroxysuccinimidyl ester of S-acetylmercaptoacetic
      acid (N-succinimidyl S-acetylmercaptoacetate (SATA)) from mercaptoacetic acid and
      is followed by the synthesis of S-acetylmercaptoacetyltriglycine from SATA,
      together requiring about 14 days. Finally, the synthesis of NHS-MAG3 from S
      acetylmercaptoacetyltriglycine requires a further 5 days. We had earlier
      described a method for the preparation of MAG3-conjugated and 99mTc-radiolabeled
      biomolecules that required elevated temperatures during postconjugation
      purification. We now report a modified method for the preparation that is
      accomplished at room temperature and therefore applicable to temperature
      sensitive biomolecules. The conjugation and radiolabeling of bovine serum albumin
      is used as an example. The conjugation and purification requires about 2-3 h and
      the radiolabeling and postlabeling purification requires about an additional 2 h.

PMID- 17446897
TI  - A protocol for conducting 7-day daily renewal tests with Lemna gibba.
AB  - Lemna gibba (a duckweed) is a freshwater macrophyte commonly used in toxicity
      testing, and Lemna spp are currently the only aquatic higher plants required for
      evaluation of pesticides under the pesticide registration guidelines of the EPA.
      The methods currently available for toxicity testing by various organizations and
      agencies, including ASTM, OECD, EPA and Environment Canada, are largely static or
      semistatic tests with unspecified renewal intervals (OECD) and may not provide a
      consistent means of exposure owing to short toxicant half-life in aquatic media,
      uptake of chemical by plants and evaporation of nutrient media. The procedure
      outlined here details a simple and efficient 7-day daily static renewal procedure
      for conducting toxicity tests with L. gibba, the appropriate end points to
      assess, the statistical criteria necessary for analyzing the toxicity data, as
      well as the steps required to culture and maintain L. gibba. This protocol is
      based on a modified version of a widely accepted static method.

PMID- 17446898
TI  - Mapping networks of physical interactions between genomic elements using 5C
      technology.
AB  - Genomic elements separated by large genomic distances can physically interact to
      mediate long-range gene regulation and other chromosomal processes. Interactions
      between genomic elements can be detected using the chromosome conformation
      capture (3C) technology. We recently developed a high-throughput adaptation of
      3C, 3C-carbon copy (5C), that is used to measure networks of millions of
      chromatin interactions in parallel. As in 3C, cells are treated with formaldehyde
      to cross-link chromatin interactions. The chromatin is solubilized, digested with
      a restriction enzyme and ligated at low DNA concentration to promote intra
      molecular ligation of cross-linked DNA fragments. Ligation products are
      subsequently purified to generate a 3C library. The 5C technology then employs
      highly multiplexed ligation-mediated amplification (LMA) to detect and amplify 3C
      ligation junctions. The resulting 5C library of ligated primers is analyzed using
      either microarray detection or ultra-high-throughput DNA sequencing. The 5C
      protocol described here can be completed in 13 d.

PMID- 17446899
TI  - Primary culture of Caenorhabditis elegans developing embryo cells for
      electrophysiological, cell biological and molecular studies.
AB  - Cell culture is an invaluable tool for investigation of basic biological
      processes. However, technical hurdles including low cell yield, poor cell
      differentiation and poor attachment to the growth substrate have limited the use
      of this tool for studies of the genetic model organism Caenorhabditis elegans.
      This protocol describes a method for the large-scale culture of C. elegans embryo
      cells. We also describe methods for in vitro RNA interference, fluorescence
      activated cell sorting of embryo cells and imaging of cultured cells for patch
      clamp electrophysiology studies. Developing embryos are isolated from gravid
      adult worms. After eggshell removal by enzymatic digestion, embryo cells are
      dissociated and plated onto glass substrates. Isolated cells terminally
      differentiate within 24 h. Analysis of gene expression patterns and cell-type
      frequency suggests that in vitro embryo cell cultures recapitulate the
      developmental characteristics of L1 larvae. Cultured embryo cells are well suited
      for physiological analysis as well as molecular and cell biological studies. The
      embryo cell isolation protocol can be completed in 5-6 h.

PMID- 17446900
TI  - Helium-neon laser irradiation stimulates cell proliferation through
      photostimulatory effects in mitochondria.
AB  - Previous reports have shown that cellular functions could be influenced by visual
      light (400-700 nm). Recent evidence indicates that cellular proliferation could
      be triggered by the interaction of a helium-neon laser (He-Ne laser, 632.8 nm)
      with the mitochondrial photoacceptor-cytochrome c oxidase. Our previous studies
      demonstrated that He-Ne irradiation induced an increase in cell proliferation,
      but not migration, in the melanoma cell line A2058 cell. The aim of this study
      was to investigate the underlying mechanisms involved in photostimulatory effects
      induced by an He-Ne laser. Using the A2058 cell as a model for cell
      proliferation, the photobiologic effects induced by an He-Ne laser were studied.
      He-Ne irradiation immediately induced an increase in mitochondrial membrane
      potential (delta psi(mt)), ATP, and cAMP via enhanced cytochrome c oxidase
      activity and promoted phosphorylation of Jun N-terminal kinase (JNK)/activator
      protein-1 (AP-1) expressions. He-Ne irradiation-induced A2058 cell proliferation
      was significantly abrogated by the addition of delta psi(mt) and JNK inhibitors.
      Moreover, treatment with an He-Ne laser resulted in delayed effects on IL-8 and
      transforming growth factor-beta1 release from A2058 cells. These results suggest
      that He-Ne irradiation elicits photostimulatory effects in mitochondria
      processes, which involve JNK/AP-1 activation and enhanced growth factor release,
      and ultimately lead to A2058 cell proliferation.

PMID- 17446901
TI  - TNF-alpha gene promoter -238G>A and -308G>A polymorphisms alter risk of psoriasis
      vulgaris: a meta-analysis.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a major proinflammatory cytokine and
      involved in the etiology of psoriasis. The -238G>A and -308G>A polymorphisms
      influence the transcription of the TNF-alpha gene and have been implicated in
      psoriasis risk. However, the results from the published studies on the
      association between TNF-alpha polymorphisms and psoriasis risk are conflicting.
      Our meta-analysis of a total of 997 psoriasis cases and 943 control subjects from
      eight published case-control studies for the -238G>A polymorphism and of 1,156
      psoriasis cases and 1,083 control subjects from 10 published case-control studies
      for the -308G>A polymorphism showed that a significantly increased risk was
      associated with the variant GA+AA genotypes of -238G>A, compared with the GG
      genotype (odds ratio (OR) 2.60, 95% confidence interval (95% CI) 1.48-4.56),
      whereas a significantly reduced psoriasis risk was associated with the variant
      GA+AA genotypes of the -308G>A compared with the GG genotype (OR 0.57, 95% CI
      0.45-0.71). Our findings suggest that TNF-alpha -238G>A and -308G>A polymorphisms
      might be used as biomarkers for psoriasis risk prediction. A single larger study
      with thousands of subjects and biochemical and biological characterization is
      warranted to evaluate further the role of -238G>A and -308G>A polymorphisms and
      psoriasis risk in a population of various ethnicities.

PMID- 17446903
TI  - Modeling, design, fabrication, and testing of a fiber Bragg grating strain sensor
      array.
AB  - The modeling, design, simulation, fabrication, calibration, and testing of a
      three-element, 15.3 cm fiber Bragg grating strain sensor array with the coherent
      optical frequency domain reflectometry (C-OFDR) interrogation technique are
      demonstrated. The fiber Bragg grating array (FBGA) is initially simulated using
      in-house software that incorporates transfer matrices. Compared to the previous
      techniques used, the transfer matrix method allows a systemwide approach to
      modeling the FBGA-C-OFDR system. Once designed and simulated, the FBGA system
      design is then imprinted into the core of a boron-germanium codoped
      photosensitive fiber using the phase mask technique. A fiber optic Fabry-Perot
      interferometric (FPI) strain gauge calibrator is then used to determine the
      strain gauge factor of a single fiber Bragg grating (FBG), and the results are
      used on the FBGA. The FPI strain gauge calibrator offers nondestructive testing
      of the FBG. To test the system, the FBGA is then attached to a 75 cm cantilever
      beam and interrogated using an incremental tunable laser. Electric strain gauges
      (ESGs) are then used to independently verify the strain measurements with the
      FBGA at various displacements of the cantilever beam. The results show that the
      peak strain error is 18% with respect to ESG results. In addition, good agreement
      is shown between the simulation and the experimental results.

PMID- 17446902
TI  - Early inflammatory changes in the "perilesional skin" of psoriatic plaques: is
      there interaction between dendritic cells and keratinocytes?
AB  - Early inflammatory changes in psoriatic plaques were investigated
      immunohistochemically by studying the normal-appearing skin adjacent to the
      plaques (perilesional skin), lesional skin, and distant uninvolved skin from
      psoriasis patients. Perilesional epidermis contained numerous CD1a-positive
      Langerhans cells, some of which expressed HLA-DR, CD83, CD80, and CD86, at the
      same time expressing Langerin. There were also numerous CD83-positive, CD11c
      positive, Langerin-negative dendritic cells (DCs) in the epidermal-dermal
      junction of perilesional skin. CD3-positive T lymphocytes were sparse in the
      perilesional skin. Perilesional epidermis expressed keratin K6 and K16,
      inflammatory keratins, and C/EBPbeta, a transcription factor related to
      inflammatory cytokines. Our results demonstrated the abundant distribution of
      activated DCs in the perilesional skin of psoriatic plaques, where early
      inflammatory changes occur in the epidermal keratinocytes, which suggests their
      involvement in the provocation of epidermal inflammation in the perilesional
      epidermis and further pathogenic roles in the formation of psoriatic plaques.

PMID- 17446904
TI  - Self-recording phenomenon in the process of reconstruction from a highly
      efficient dynamic hologram on azo-dye-colored material with powerful Weigert's
      effect.
AB  - The dynamic process of highly efficient holographic recording of two orthogonally
      circularly polarized plane light waves on the azo-dye-colored gelatin with
      powerful Weigert's effect is investigated. The investigation has shown that at
      some ratios of the intensities of the recording waves the self-recording
      phenomenon during the reconstruction process by the same actinic light
      (lambda=488.0 nm) is observed, and the diffractive efficiency for the probe light
      (lambda=632.8 nm) of an already fully recorded hologram increases again almost
      instantly after blocking one of the recording beams of low intensity. The maximum
      diffractive efficiency reaches 40%-45% in this case.

PMID- 17446905
TI  - Design and fabrication of a high-efficiency extreme-ultraviolet binary phase-only
      computer-generated hologram.
AB  - As the development of extreme-ultraviolet (EUV) lithography progresses, interest
      grows in the extension of traditional optical components to the EUV regime. The
      strong absorption of EUV by most materials and its extremely short wavelength,
      however, make it very difficult to implement many components that are commonplace
      in the longer wavelength regimes. One such component is the diffractive optical
      element used, for example, in illumination systems to efficiently generate
      modified pupil fills. The fabrication and characterization of an EUV binary phase
      only computer-generated hologram is demonstrated, allowing arbitrary far-field
      diffraction patterns to be generated. Based on reflective architecture, the
      fabricated device is extremely efficient. Based on an identically fabricated null
      hologram, the absolute efficiency into one diffracted order of 22% has been
      demonstrated. In the case where axially symmetric diffraction patterns are
      desired (both positive and negative diffraction orders can be used), the
      efficiency can be twice as high.

PMID- 17446906
TI  - Efficient Fresnel x-ray optics made simple.
AB  - A practical design for upcoming spaceborne x-ray telescopes with ultrahigh
      angular resolution is proposed. Particular attention is directed to technological
      simplicity and robust as well as cheap components. Based on dispersion corrected
      Fresnel lenses, an optimized arrangement will be identified with respect to the
      instrumental sensitivity for a given focal spot size. We show that this optical
      Gamow peak essentially depends on the radial transmission profile of a
      diffractive-refractive aperture. Examples for energies above 4 keV illustrate
      astronomical capabilities for large-scale compact and segmented objectives as
      well. The spectral and spatial resolutions of conventional semiconductor
      detectors are very well matched to imaging characteristics of those achromatic
      lenses. The constraints to fabrication techniques using most promising materials
      like Li, Be, and plastics are discussed.

PMID- 17446907
TI  - Design of a bright polarized head-mounted projection display.
AB  - In optical see-through head-mounted displays, it has been a common challenge that
      the displayed image lacks brightness and contrast compared with the direct view
      of a real-world scene. Consequently, such displays are usually used in dimmed
      lighting conditions, which limits the feasibility of applying such information
      displays outdoors or in scenarios where well-lit environments, such as in
      operation rooms, are required. The lack of image brightness is aggravated in the
      design of a see-through head-mounted projection display (HMPD). For instance, the
      overall flux transfer efficiency of existing HMPD designs is less than 10%. The
      design of a polarized head-mounted projection display (p-HMPD) is presented. The
      images of a p-HMPD system can potentially be three times brighter than those in
      existing HMPD designs. It is further demonstrated that the p-HMPD design is able
      to dramatically improve image brightness, contrast, and color vividness with
      experimental results. Finally, the design of a compact optical system and helmet
      prototype is described.

PMID- 17446908
TI  - Accurate measurement method of Fabry-Perot cavity parameters via optical transfer
      function.
AB  - It is shown how the transfer function from frequency noise to a Pound-Drever-Hall
      signal for a Fabry-Perot cavity can be used to accurately measure cavity length,
      cavity linewidth, mirror curvature, misalignments, laser beam shape mismatching
      with resonant beam shape, and cavity impedance mismatching with respect to
      vacuum.

PMID- 17446909
TI  - Geometrical considerations in analyzing isotropic or anisotropic surface
      reflections.
AB  - The bidirectional reflectance distribution function (BRDF) represents the
      evolution of the reflectance with the directions of incidence and observation.
      Today BRDF measurements are increasingly applied and have become important to the
      study of the appearance of surfaces. The representation and the analysis of BRDF
      data are discussed, and the distortions caused by the traditional representation
      of the BRDF in a Fourier plane are pointed out and illustrated for two
      theoretical cases: an isotropic surface and a brushed surface. These
      considerations will help characterize either the specular peak width of an
      isotropic rough surface or the main directions of the light scattered by an
      anisotropic rough surface without misinterpretations. Finally, what is believed
      to be a new space is suggested for the representation of the BRDF, which avoids
      the geometrical deformations and in numerous cases is more convenient for BRDF
      analysis.

PMID- 17446910
TI  - Multiwavelength electronic speckle pattern interferometry for surface shape
      measurement.
AB  - Profilometry by electronic speckle pattern interferometry with multimode diode
      lasers is both theoretically and experimentally studied. The multiwavelength
      character of the laser emission provides speckled images covered with
      interference fringes corresponding to the surface relief in single-exposure
      processes. For fringe pattern evaluation, variations of the phase-stepping
      technique are investigated for phase mapping as a function of the number of laser
      modes. Expressions for two, three, and four modes in four and eight stepping are
      presented, and the performances of those techniques are compared in the
      experiments through the surface shaping of a flat bar. The surface analysis of a
      peach points out the possibility of applying the technique in the quality control
      of food production and agricultural research.

PMID- 17446911
TI  - Acousto-optic tunable filter imaging spectrometer with full Stokes polarimetric
      capability.
AB  - Polarization is an important addition to spectral imaging in detecting and
      identifying objects of interest, and simple linear polarization measurements are
      often inadequate. Full polarization analysis can give additional information for
      discrimination where the polarization state is completely described by the Stokes
      parameters. An acousto-optic tunable filter (AOTF) imaging system was built
      incorporating two liquid-crystal variable retarders (LCVRs) that can provide
      complete spectral-polarimetric analysis, and it is believed to be the first
      demonstration of a full Stokes polarimetric AOTF spectral imaging system with no
      moving parts. It is also shown that a single LCVR cannot provide all the Stokes
      parameters.

PMID- 17446912
TI  - Data analysis for a rotating quarter-wave, far-infrared Stokes polarimeter.
AB  - Data analysis techniques are reviewed and extended for the measurement of the
      Stokes vector of partially or completely polarized radiation by the rotating
      quarter-wave method. It is shown that the conventional technique, based on the
      Fourier analysis of the recorded signal, can be efficiently replaced by a
      weighted least-squares best fit, so that the different accuracy of the measured
      data can be taken into account to calculate the measurement errors of the Stokes
      vector elements. Measurement errors for the polarization index P and for the
      azimuth and ellipticity angles psi and chi of the radiation are also calculated
      by propagation error theory. For those cases in which the above technique gives a
      nonphysical Stokes vector (i.e., with a polarization degree of P>1) a constrained
      least-squares best fit is introduced, and it is shown that in this way a Stokes
      vector with P = 1 (rather than P<or=1) is always obtained. In addition an
      analysis technique useful to remove from the measured data systematic errors due
      to initial misalignment of the rotating quarter-wave axis is described. Examples
      of experimental Stokes vectors obtained by the above techniques during the
      characterization of components for a far-infrared polarimeter at lambda=118.8
      microm for applications in plasma diagnostics are presented and discussed.
      Finally the problem of the experimental determination of physically consistent
      Mueller matrices (i.e., of Mueller matrices for which the transformed Stokes
      vector has always P<or=1) is discussed, and it is shown that for simple Mueller
      matrices of the ABCD type, whose elements can be determined by the measurement of
      a single Stokes vector, the imposed P<or=1 constraint gives a sufficient
      condition for physical consistency. On the other hand, the same constraint, when
      imposed to the set of four basic Stokes vectors conventionally measured for the
      determination of a full 16-element Mueller matrix, gives only a necessary but not
      a sufficient condition.

PMID- 17446913
TI  - Light diffusion model for determination of optical properties of rectangular
      parallelepiped highly scattering media.
AB  - A method to determine the absorption and reduced scattering coefficients of
      rectangular parallelepiped highly scattering media from frequency-domain photon
      migration measurements is presented. An analytical model for photon diffusion
      propagation in the rectangular parallelepiped media is established using the
      method of images and extrapolated boundary conditions. This present technique has
      simplicity, accuracy, and rapid computability as compared with the Monte Carlo or
      finite element methods. The theoretical predictions are verified with
      experimental measurements using a white polyacetal resin, and the errors
      introduced by using the slab geometry for the optical property determination are
      identified.

PMID- 17446914
TI  - Efficient optimization of multilayer coatings for ultrafast optics using analytic
      gradients of dispersion.
AB  - A fully analytic method for computing gradients of dispersion (to any order) for
      a dielectric multilayer coating is developed, and it is demonstrated how group
      delay gradients can be used to optimize the dispersion of such a filter. The
      algorithm complexity is linear with the number of layers and quadratic in
      dispersion order. To our knowledge, this is the first published algorithm for
      computing exact analytic gradients of dispersion. We show an approximation that
      speeds up the computation significantly, making it linear in dispersion order.
      MATLAB and C code implementing the algorithms are made available.

PMID- 17446915
TI  - Figure tolerance of a Wolter type I mirror for a soft-x-ray microscope.
AB  - The demand for an x-ray microscope has received much attention because of the
      desire to study living cells at a high resolution and in a hydrated environment.
      A Wolter type I mirror used for soft-x-ray microscope optics has many advantages.
      From the mirror fabrication point of view, it is necessary to perform tolerance
      analysis, particularly with respect to figure errors that considerably degrade
      the image quality. The figure tolerance of a Wolter type I mirror for a
      biological application in terms of the image quality and the state-of-the-art
      fabrication technology is discussed. The figure errors rapidly destroyed the
      image quality, and the required slope error depended on the detector used in the
      soft-x-ray microscope.

PMID- 17446916
TI  - Multiscale windowed Fourier transform for phase extraction of fringe patterns.
AB  - A multiscale windowed Fourier transform for phase extraction of fringe patterns
      is presented. A local stationary length of signal is used to control the window
      width of a windowed Fourier transform automatically, which is measured by an
      instantaneous frequency gradient. The instantaneous frequency of the fringe
      pattern is obtained by detecting the ridge of the wavelet transform. The
      numerical simulation and experiment have proved the validity of this method. The
      combination of the windowed Fourier transform and the wavelet transform makes the
      extracted phase more precise than other methods.

PMID- 17446917
TI  - Multiple rotation assessment through isothetic fringes in speckle photography.
AB  - The use of different pupils for storing each speckled image in speckle
      photography is employed to determine multiple in-plane rotations. The method
      consists of recording a four-exposure specklegram where the rotations are done
      between exposures. This specklegram is then optically processed in a whole field
      approach rendering isothetic fringes, which give detailed information about the
      multiple rotations. It is experimentally demonstrated that the proposed
      arrangement permits the depiction of six isothetics in order to measure either
      six different angles or three nonparallel components for two local general in
      plane displacements.

PMID- 17446918
TI  - Information throughput of photorefractive spatial solitons in the
      telecommunication range.
AB  - Photorefractive spatial solitons are attractive elements because they can be used
      as controllable optical interconnectors for all-optical devices. To our
      knowledge, until now their properties were investigated in terms of energy
      transportation. We suggest considering photorefractive spatial solitons as
      optically induced information channels. The experimental technique to measure the
      information throughput of photorefractive spatial solitons in accordance with
      Shannon's definition was developed and demonstrated by us. We experimentally
      demonstrated that in the wavelength range of 1520-1630 nm it can be estimated as
      large as approximately 90 Tbits/s. We also experimentally demonstrate a
      measurement of the group-velocity dispersion and show the limitation of the pulse
      transfer rate of the induced waveguides to approximately 6.2 THz.

PMID- 17446919
TI  - Application of the SKYRAD Improved Langley plot method for the in situ
      calibration of CIMEL Sun-sky photometers.
AB  - The in situ procedure for determining the solar calibration constants, originally
      developed for the PREDE Sun-sky radiometers and based on a modified version of
      the Langley plot, was applied to a CIMEL instrument located in Valencia, Spain,
      not integrated into AERONET. Taking into account the different mechanical and
      electronic characteristics of the two radiometers, the method was adapted to the
      characteristics of the CIMEL instrument. The iterative procedure for the
      determination of the solar calibration constants was applied to a 3-year data
      set. The results were compared with the two sets of experimental calibration
      constants determined during this period using the standard Langley plot method.
      The agreement was found to be consistent with the experimental errors, and the
      method can definitely also be used to determine the solar calibration constant
      for the CIMEL instrument, improving its calibration. The method can be used
      provided the radiometer is previously calibrated for diffuse radiance using a
      standard lamp.

PMID- 17446920
TI  - Theoretical study of cw to short pulse conversion in an active cw-injected ring
      cavity with a Yb3+:YAG amplifier.
AB  - The short laser pulse generated from an active cw-injected ring cavity with
      Yb3+:YAG crystal, which is treated as the homogeneously broadened amplifier, is
      studied theoretically. Based on the derived results, the impacts of the amplifier
      length, the seeding laser intensity and frequency, the pump intensity, the
      efficiency of the acousto-optic modulator (AOM), and the frequency shift
      generated by the AOM on the performance of the laser pulse are analyzed.

PMID- 17446921
TI  - Effect of diode wavelength broadening in a diode end-pumped solid-state
      amplifier.
AB  - The effect of the spectral broadening in cw diode pumping and the wavelength
      shift in pulsed pumping of a solid-state laser is investigated theoretically. A
      very simple model allowing the computation of the reduction of the absorbed pump
      energy is developed. The results are applied to an ytterbium-doped solid-state
      laser and should be fruitful for amplifier and laser design.

PMID- 17446922
TI  - Anomalous celestial polarization caused by forest fire smoke: why do some insects
      become visually disoriented under smoky skies?
AB  - The effects of forest fire smoke on sky polarization and animal orientation are
      practically unknown. Using full-sky imaging polarimetry, we therefore measured
      the celestial polarization pattern under a smoky sky in Fairbanks, Alaska, during
      the forest fire season in August 2005. It is quantitatively documented here that
      the celestial polarization, a sky attribute that is necessary for orientation of
      many polarization-sensitive animal species, above Fairbanks on 17 August 2005 was
      in several aspects anomalous due to the forest fire smoke: (i) The pattern of the
      degree of linear polarization p of the reddish smoky sky differed considerably
      from that of the corresponding clear blue sky. (ii) Due to the smoke, p of
      skylight was drastically reduced (p(max)<or=14%, p(average)<or=8%). (iii)
      Depending on wavelength and time, the Arago, Babinet, and Brewster neutral points
      of sky polarization had anomalous positions. We suggest that the disorientation
      of certain insects observed by Canadian researchers under smoky skies during the
      forest fire season in August 2003 in British Columbia was the consequence of the
      anomalous sky polarization caused by the forest fire smoke.

PMID- 17446923
TI  - Multiparameter retrieval of water optical properties from above-water remote
      sensing reflectance using the simulated annealing algorithm.
AB  - Water-leaving radiance, measured just above the ocean surface, contains important
      information about near-surface or subsurface processes that occur on or below the
      deep ocean and coastal water. As such, retrieving seawater inherent optical
      properties (IOPs) is an important step to determining water type, subsurface
      light field, turbidity, pigment concentration, and sediment loading. However, the
      retrieval (or inversion) of seawater IOPs from just above water radiance
      measurements is a multiparameter nonlinear problem that is difficult to solve by
      conventional optimization methods. The applicability of the simulated annealing
      algorithm (SA) is explored as a nonlinear global optimizer to solve this
      multiparameter retrieval problem. The SA algorithm is combined with widely known
      semianalytical relations for seawater's IOPs to parameter invert these properties
      from simulated and measured water-leaving reflectance spectra. Furthermore, given
      the versatility of the SA algorithm, the scheme is extended to retrieve water
      depth from input reflectance data. Extensive tests and comparisons with in situ
      and simulated data sets compiled by the International Ocean-Color Coordinating
      Group are presented. Field data include reflectance spectra acquired with a
      handheld GER 1500 spectroradiometer and absorption measurements, performed with
      the AC-9 instrument on waters around Singapore's nearby islands.

PMID- 17446924
TI  - Image reconstruction in optical tomography in the presence of coupling errors.
AB  - Image reconstruction in optical tomography is a nonlinear and generally ill-
      posed inverse problem. Noise in the measured surface data can give rise to
      substantial artifacts in the recovered volume images of optical coefficients.
      Apart from random shot noise caused by the limited number of photons detected at
      the measurement site, another class of systematic noise is associated with losses
      specific to individual source and detector locations. A common cause for such
      losses in data acquisition systems based on fiber-optic light delivery is the
      imperfect coupling between the fiber tips and the skin of the patient because of
      air gaps or surface moisture. Thus the term coupling errors was coined for this
      type of data noise. However, source and detector specific errors can also occur
      in noncontact measurement systems not using fiber-optic delivery, for example,
      owing to local skin pigmentation, hair and hair follicles, or instrumentation
      calibration errors. Often it is not possible to quantify coupling effects in a
      way that allows us to remove them from the data or incorporate them into the
      light transport model. We present an alternative method of eliminating coupling
      errors by regarding the complex-valued coupling factors for each source and
      detector as unknowns in the reconstruction process and recovering them
      simultaneously with the images of absorption and scattering. Our method takes
      into account the possibility that coupling effects have an influence on both the
      amplitude and the phase shift of the measurements. Reconstructions from simulated
      and experimental phantom data are presented, which show that including the
      coupling coefficients in the reconstruction greatly improves the recovery of
      absorption and scattering images.

PMID- 17446925
TI  - Image reconstruction scheme that combines modified Newton method and efficient
      initial guess estimation for optical tomography of finger joints.
AB  - What we believe to be a novel 3D diffuse optical tomography scheme is developed
      to reconstruct images of both absorption and scattering coefficients of finger
      joint systems. Compared with our previous reconstruction method, the improved 3D
      algorithm employs both modified Newton methods and an enhanced initial value
      optimization scheme to recover the optical properties of highly heterogeneous
      media. The developed approach is tested using simulated, phantom, and in vivo
      measurement data. The recovered results suggest that the improved approach is
      able to provide quantitatively better images than our previous algorithm for
      optical tomography reconstruction.

PMID- 17446926
TI  - Experimental prediction of the wavelength-dependent path-length factor for
      optical intrinsic signal analysis.
AB  - Analysis of the optical intrinsic signal of an exposed cortex has been applied to
      measurement of functional brain activation. It is important for accurate
      measurement of concentration changes in oxygenated hemoglobin and deoxygenated
      hemoglobin to consider the wavelength dependence of the mean optical path lengths
      for the reflectance of cortical tissue. A method is proposed to experimentally
      estimate the wavelength dependence of the mean optical path length in cortical
      tissue from the multispectral reflectance of the exposed cortex without any
      additional instruments. The trend in the wavelength dependence of the mean
      optical path length estimated by the proposed method agrees with that estimated
      by the model-based prediction, whereas the magnitude of the wavelength dependence
      predicted by the proposed method is greater than that of the model-based
      prediction. The experimentally predicted mean optical path length minimizes the
      difference in the measured changes in the concentrations of the oxygenated
      hemoglobin and deoxygenated hemoglobin calculated from different wavelength
      pairs.

PMID- 17446927
TI  - Tomographic bioluminescence imaging with varying boundary conditions.
AB  - Three-dimensional bioluminescence imaging is an emerging technique that can be
      used to monitor molecular events in intact living systems. The inverse problem of
      3D bioluminescence imaging does not have a unique solution because it requires
      reconstruction of a 3D source function from a 2D one. A novel approach that
      addresses this problem with the aid of a simple experimental setup and solves the
      uniqueness problem of the solution for a monochromatic measurement set is
      suggested here. The approach is verified numerically by reconstructing
      bioluminescent objects of various shapes embedded inside highly scattering media,
      such as biological tissue.

PMID- 17446928
TI  - Intraoperative monitoring of depth-dependent hemoglobin concentration changes
      during carotid endarterectomy by time-resolved spectroscopy.
AB  - By measuring the adult human head during carotid endarterectomy, we investigate
      the depth sensitivity of two methods for deriving the absorption coefficient
      changes (Dmu(a)) from time-resolved reflectance data to absorption changes in
      inhomogeneous media: (1) the curve-fitting method based on the diffusion equation
      (DE-fit method) and (2) the time-independent calculation based on the modified
      Lambert-Beer law (MLB method). Remarkable differences in the determined values of
      Dmu(a) caused by clamping the external carotid artery and subsequently clamping
      the common carotid artery were observed between the methods. The DE-fit method
      was more sensitive to mu(a) changes in cerebral tissues, whereas the MLB method
      was rather sensitive to mu(a) changes in the extracerebral tissues. Our results
      indicated that the DE-fit was useful for monitoring the cerebral blood
      circulation and oxygenation during neurosurgical operations. In addition, the
      combined evaluation of mu(a) changes with the DE-fit and MLB methods will provide
      us with more available information about the hemodynamic changes in the depth
      direction.

PMID- 17446929
TI  - The p63/p73 network mediates chemosensitivity to cisplatin in a biologically
      defined subset of primary breast cancers.
AB  - Breast cancers lacking estrogen and progesterone receptor expression and Her2
      amplification exhibit distinct gene expression profiles and clinical features,
      and they comprise the majority of BRCA1-associated tumors. Here we demonstrated
      that the p53 family member p63 controls a pathway for p73-dependent cisplatin
      sensitivity specific to these "triple-negative" tumors. In vivo, DeltaNp63 and
      TAp73 isoforms were coexpressed exclusively within a subset of triple-negative
      primary breast cancers that commonly exhibited mutational inactivation of p53.
      The DeltaNp63alpha isoform promoted survival of breast cancer cells by binding
      TAp73 and thereby inhibiting its proapoptotic activity. Consequently, inhibition
      of p63 by RNA interference led to TAp73-dependent induction of proapoptotic Bcl-2
      family members and apoptosis. Breast cancer cells expressing DeltaNp63alpha and
      TAp73 exhibited cisplatin sensitivity that was uniquely dependent on TAp73. Thus,
      in response to treatment with cisplatin, but not other chemotherapeutic agents,
      TAp73 underwent c-Abl-dependent phosphorylation, which promoted dissociation of
      the DeltaNp63alpha/TAp73 protein complex, TAp73-dependent transcription of
      proapoptotic Bcl-2 family members, and apoptosis. These findings define p63 as a
      survival factor in a subset of breast cancers; furthermore, they provide what we
      believe to be a novel mechanism for cisplatin sensitivity in these triple
      negative cancers, and they suggest that such cancers may share the cisplatin
      sensitivity of BRCA1-associated tumors.

PMID- 17446930
TI  - Inhibition of p38 alpha MAPK rescues cardiomyopathy induced by overexpressed beta
      2-adrenergic receptor, but not beta 1-adrenergic receptor.
AB  - We examined the role of p38alpha MAPK in mediating cardiomyopathy in mice
      overexpressing beta(1)-adrenergic receptor (beta(1)-AR) or beta(2)-AR by mating
      them with dominant-negative p38alpha (DNp38alpha) MAPK mice. Both beta(1)-AR and
      beta(2)-AR Tg mice had enhanced LV ejection fraction (LVEF) as young adults and
      developed similar cardiomyopathy at 11-15 months, characterized by reduced LVEF,
      myocyte hypertrophy, fibrosis, and apoptosis. We inhibited p38alpha MAPK by
      mating beta(1)-AR Tg and beta(2)-AR Tg mice with DNp38alpha MAPK mice, which
      rescued the depressed LVEF and reduced apoptosis and fibrosis in bigenic beta(2)
      AR x DNp38alpha MAPK mice, but not bigenic beta(1)-AR x DNp38alpha MAPK mice, and
      failed to reduce myocyte hypertrophy in either group. G(salpha) was increased in
      both beta(1)-AR Tg and beta(2)-AR Tg mice and was still present in bigenic
      beta(1)-AR x DNp38alpha MAPK mice, but not bigenic beta(2)-AR x DNp38alpha MAPK
      mice. This suggests that p38alpha MAPK is one critical downstream signal for the
      development of cardiomyopathy following chronic beta(2)-AR stimulation, but other
      kinases may be more important in ameliorating the adverse effects of chronic
      beta(1)-AR stimulation.

PMID- 17446931
TI  - Antibody-enhanced cross-presentation of self antigen breaks T cell tolerance.
AB  - We have developed a model of autoimmunity to investigate autoantibody-mediated
      cross-presentation of self antigen. RIP-mOVA mice, expressing OVA in pancreatic
      beta cells, develop severe autoimmune diabetes when given OT-I cells (OVA
      specific CD8(+) T cells) and anti-OVA IgG but not when given T cells alone. Anti
      OVA IgG is not directly injurious to the islets but rather enhances cross
      presentation of apoptotic islet antigen to the OT-I cells, leading to their
      differentiation into potent effector cells. Antibody-driven effector T cell
      activation is dependent on the presence of activating Fc receptors for IgG
      (FcgammaRs) and cross-priming DCs. As a consequence, diabetes incidence and
      severity was reduced in mice lacking activating FcgammaRs. An intact complement
      pathway was also required for disease development, as C3 deficiency was also
      partially protective. C3-deficient animals exhibited augmented T cell priming
      overall, indicating a proinflammatory role for complement activation after the T
      cell priming phase. Thus, we show that autoreactive antibody can potently enhance
      the activation of effector T cells in response to cross-presented self antigen,
      thereby contributing to T cell-mediated autoimmunity.

PMID- 17446932
TI  - Activation of MAPK pathways links LMNA mutations to cardiomyopathy in Emery
      Dreifuss muscular dystrophy.
AB  - Mutations in LMNA, which encodes nuclear Lamins A and C cause diseases affecting
      various organs, including the heart. We have determined the effects of an Lmna
      H222P mutation on signaling pathways involved in the development of
      cardiomyopathy in a knockin mouse model of autosomal dominant Emery-Dreifuss
      muscular dystrophy. Analysis of genome-wide expression profiles in hearts using
      Affymetrix GeneChips showed statistically significant differences in expression
      of genes in the MAPK pathways at the incipience of the development of clinical
      disease. Using real-time PCR, we showed that activation of MAPK pathways preceded
      clinical signs or detectable molecular markers of cardiomyopathy. In heart tissue
      and isolated cardiomyocytes, there was activation of MAPK cascades and downstream
      targets, implicated previously in the pathogenesis of cardiomyopathy. Expression
      of H222P Lamin A in cultured cells activated MAPKs and downstream target genes.
      Activation of MAPK signaling by mutant A-type lamins could be a cornerstone in
      the development of heart disease in autosomal dominant Emery-Dreifuss muscular
      dystrophy.

PMID- 17446933
TI  - Constraints in antigen presentation severely restrict T cell recognition of the
      allogeneic fetus.
AB  - How the fetus escapes rejection by the maternal immune system remains one of the
      major unsolved questions in transplantation immunology. Using a system to
      visualize both CD4+ and CD8+ T cell responses during pregnancy in mice, we find
      that maternal T cells become aware of the fetal allograft exclusively through
      "indirect" antigen presentation, meaning that T cell engagement requires the
      uptake and processing of fetal/placental antigen by maternal APCs. This reliance
      on a relatively minor allorecognition pathway removes a major threat to fetal
      survival, since it avoids engaging the large number of T cells that typically
      drive acute transplant rejection through their ability to directly interact with
      foreign MHC molecules. Furthermore, CD8+ T cells that indirectly recognize
      fetal/placental antigen undergo clonal deletion without priming for cytotoxic
      effector function and cannot induce antigen-specific fetal demise even when
      artificially activated. Antigen presentation commenced only at mid-gestation, in
      association with the endovascular invasion of placental trophoblasts and the
      hematogenous release of placental debris. Our results suggest that limited
      pathways of antigen presentation, in conjunction with tandem mechanisms of immune
      evasion, contribute to the unique immunological status of the fetus. The
      pronounced degree of T cell ignorance of the fetus also has implications for the
      pathophysiology of immune-mediated early pregnancy loss.

PMID- 17446934
TI  - Macrophages and neutrophils are the targets for immune suppression by
      glucocorticoids in contact allergy.
AB  - Glucocorticoids (GCs) are widely used in the treatment of allergic skin
      conditions despite having numerous side effects. Here we use Cre/loxP-engineered
      tissue- and cell-specific and function-selective GC receptor (GR) mutant mice to
      identify responsive cell types and molecular mechanisms underlying the
      antiinflammatory activity of GCs in contact hypersensitivity (CHS). CHS was
      repressed by GCs only at the challenge phase, i.e., during reexposure to the
      hapten. Inactivation of the GR gene in keratinocytes or T cells of mutant mice
      did not attenuate the effects of GCs, but its ablation in macrophages and
      neutrophils abolished downregulation of the inflammatory response. Moreover, mice
      expressing a DNA binding-defective GR were also resistant to GC treatment. The
      persistent infiltration of macrophages and neutrophils in these mice is explained
      by an impaired repression of inflammatory cytokines and chemokines such as IL
      1beta, monocyte chemoattractant protein-1, macrophage inflammatory protein-2, and
      IFN-gamma-inducible protein 10. In contrast TNF-alpha repression remained intact.
      Consequently, injection of recombinant proteins of these cytokines and chemokines
      partially reversed suppression of CHS by GCs. These studies provide evidence that
      in contact allergy, therapeutic action of corticosteroids is in macrophages and
      neutrophils and that dimerization GR is required.

PMID- 17446935
TI  - Interactions of antitumor triazoloacridinones with DNA.
AB  - Triazoloacridinones (TA) are a new group of potent antitumor compounds, from
      which the most active derivative, C-1305, has been selected for extended
      preclinical trials. This study investigated the mechanism of TA binding to DNA.
      Initially, for selected six TA derivatives differing in chemical structures as
      well as cytotoxicity and antitumor activity, the capability of noncovalent DNA
      binding was analyzed. We showed that all triazoloacridinones studied stabilized
      the DNA duplex at a low-concentration buffer but not at a salt concentration
      corresponding to that in cells. DNA viscometric studies suggested that
      intercalation to DNA did not play a major role in the mechanism of the cytotoxic
      action of TA. Studies involving cultured cells revealed that triazoloacridinone C
      1305 after previous metabolic activation induced the formation of interstrand
      crosslinks in DNA of some tumor and fibroblast cells in a dose dependent manner.
      However, the detection of crosslink formation was possible only when the activity
      of topoisomerase II in cells was lowered. Furthermore, it was impossible to
      validate the relevance of the ability to crosslink DNA to biological activity of
      TA derivatives.

PMID- 17446936
TI  - Structure and functions of plant calcium-dependent protein kinases.
AB  - Calcium ions as second messengers play an essential role in many important
      cellular processes. In plants, transient changes in calcium content in the
      cytosol (calcium signatures) have been observed during growth, development and
      under stress conditions. Such diverse functions require many different calcium
      sensors. One of the largest and most differentiated group of calcium sensors are
      protein kinases, among them calcium-dependent protein kinases (CDPKs) which were
      identified only in plants and protists. CDPKs have a regulatory domain which is
      able to bind calcium ions. For regulation of CDPKs activities not only calcium
      ions but also specific phospholipids and autophosphorylation are responsible.
      CDPKs have many different substrates, which reflects the diversity of their
      functions. Potential protein substrates of CDPK are involved in carbon and
      nitrogen metabolism, phospholipid synthesis, defense responses, ion and water
      transport, cytoskeleton organization, transcription and hormone responses.
      Presently, participation of CDPKs in stress signal transduction pathways (e.g.,
      cold, drought, high salinity, wounding) is intensively studied in many
      laboratories. An intriguing, but still not fully clarified problem is the cross
      talk via CDPKs among different signaling pathways that enables signal integration
      at different levels and ensure appropriate downstream responses.

PMID- 17446937
TI  - From Edinburgh to Thaba Nchu - the stories of early black doctors in South
      Africa.

PMID- 17446938
TI  - Conscious sedation versus monitored anaesthesia care.

PMID- 17446939
TI  - Utilisation of pathology procedures.

PMID- 17446940
TI  - Medicines Control Council and registration backlog of antiretrovirals.

PMID- 17446941
TI  - ART revitalises beleaguered nurses - for now.

PMID- 17446942
TI  - Zimbabwe police treat doctors, lawyers with contempt.

PMID- 17446943
TI  - TB treatment guidelines begin to impact.

PMID- 17446944
TI  - Life-threatening angio-oedema and death associated with the ACE inhibitor
      enalapril.

PMID- 17446945
TI  - Fatal vascular retroperitoneal injury following bone marrow biopsy.

PMID- 17446946
TI  - Assessing scimitar syndrome - use of MRI and MRA.

PMID- 17446947
TI  - Awaking a sleeping epidemic.

PMID- 17446948
TI  - Pioneer black doctors in South Africa, 1883 - 1915.

PMID- 17446950
TI  - Antibiotic resistance in hospitals - are surveillance data of any value?

PMID- 17446951
TI  - The need for appropriate critical care service provision at non-tertiary
      hospitals in South Africa.

PMID- 17446952
TI  - Antimicrobial susceptibility profile of selected bacteraemic pathogens from
      private institutions in South Africa.
AB  - OBJECTIVES: The National Antimicrobial Surveillance Forum is a continuous
      surveillance organisation comprising all academic/public and private sector
      laboratories in South Africa. METHODS: The antibiotic susceptibility of blood
      culture isolates of Escherichia coli, Klebsiella pneumoniae, Enterobacter
      species, Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus
      aureus from patients in private hospitals in five major centres were
      investigated. Antimicrobial susceptibility tests were performed by 12
      participating laboratories according to the Clinical and Laboratory Standards
      Institute (CLSI) guidelines. Extended-spectrum b-lactamase (ESBL) production was
      determined in selected species of Enterobacteriaceae irrespective of source.
      RESULTS: The overall prevalence of ampicillin resistance in blood culture
      isolates of E. coli (N = 471) was 84%, and 20% were resistant to the
      fluoroquinolones. Considerable geographical differences were noted between the
      centres with regard to the K. pneumoniae (N = 636) resistance rates for
      ceftriaxone and/or cefotaxime (39 - 87%). The most active agents in the
      Enterobacter spp. (N = 244) were imipenem/meropenem, ertapenem, ciprofloxacin,
      levofloxacin and cefepime, with 100%, 94%, 88%, 87% and 80% susceptibility,
      respectively. Carbapenem resistance in P. aeruginosa (N = 382) varied between 42%
      and 45%, and in the case of A. baumannii (N = 190) resistance varied between 32%
      and 33% for meropenem and imipenem respectively. The nationwide incidence of
      oxacillin resistance in S. aureus (N = 629) was 36%. Overall, the prevalence of
      ESBL production among all isolates of K. pneumoniae was 26% (N = 7 514), while in
      Enterobacter spp. it was 12% (N = 4 031) and in E. coli 5% (N = 28 412).
      CONCLUSIONS: The data highlight the widespread problem of antibiotic resistance
      among important bacteraemic pathogens in private institutions in South Africa.
      Continued surveillance is vital to guide appropriate empirical therapy for
      invasive infections.

PMID- 17446953
TI  - A survey of hypertensive practices at two community health centres in Cape Town.
AB  - BACKGROUND: Control of hypertension remains an elusive goal, but doctors' non
      compliance with guidelines, patient attitudes and adherence to treatment, and
      poor delivery of care at clinics are important contributing factors. OBJECTIVES:
      To determine the overall quality of hypertensive care, and compliance with
      current hypertension guidelines at community health centres (CHCs) in the Western
      Cape. METHODS: Consecutive patients attending hypertension clinics at two CHCs
      were selected to participate. A questionnaire was designed to determine patient
      demographics, doctors' compliance with hypertension guidelines, factors leading
      to treatment non-adherence, and delivery of care. Accuracy of blood pressure (BP)
      recording was evaluated by comparing the clinic BP with that measured using an
      approved manometer. RESULTS: One hundred and sixty-one patients were evaluated,
      100 from CHC 1 and 61 from CHC 2. There was no difference in both control
      systolic and diastolic BP measured by the hypertension nurse (147.9 v. 144.8
      mmHg, p = 0.45, and 89.3 v. 85.6 mmHg, p = 0.14) respectively. All clinic BP
      readings were recorded to the nearest 10 mmHg mercury. The difference in both
      systolic and diastolic BP > 10 mmHg between the clinic and control BP was
      significantly greater at CHC 2 than CHC 1 (28% v. 56%, p = 0.005, and 43% v. 64%,
      p = 0.007) respectively. Overall, 39.8% of patients had a systolic and diastolic
      BP < 140 and < 90 mmHg. The mean number of antihypertensive drugs was 2.4 per
      patient. The use of non-steroidal anti-inflammatory drugs (NSAIDs) and tricyclic
      antidepressants was high at both centres, and few patients underwent basic
      investigations, lifestyle interventions, risk stratification or global
      cardiovascular risk reduction. CONCLUSIONS: 39.8% of patients achieved a BP <
      140/90 mmHg. There is significant scope for improvement in prescription of
      medication, application of uniform lifestyle changes, and avoidance of NSAIDs and
      tricyclic antidepressants. Major deficiencies were identified in BP measurement,
      assessment of target organ damage, risk stratification and the reduction of
      overall cardiovascular risk.

PMID- 17446954
TI  - Peripheral arterial disease - high prevalence in rural black South Africans.
AB  - BACKGROUND: The prevalence of peripheral arterial disease (PAD) worldwide has
      been estimated at between 4.5% and 29%. PAD has been associated with male gender,
      advanced age, diabetes, hypertension, hypercholesterolaemia and smoking. Clinical
      experience with amputations at Mthatha General Hospital, a district hospital in
      the Eastern Cape, suggests that PAD is common, but the actual prevalence has not
      been determined. The Eastern Cape is a rural area and patients attending the
      hospital are mostly Xhosa-speakers. OBJECTIVES: To assess the prevalence of PAD
      and associated risk factors among patients attending the hospital. METHODS: Five
      hundred and forty-two patients over 50 years of age attending the outpatient
      department were systematically selected. Gender, body mass index (BMI), blood
      pressure, capillary blood glucose and smoking status were determined. The ankle
      brachial pressure index (ABPI) was measured by Doppler ultrasound, and PAD was
      defined as a ratio less than 0.9. RESULTS: Of 542 patients (315 females, 227
      males), 159 (29.3%) had an ABPI of less than 0.9. The mean age was 62.4 years and
      the range 50 - 95 years. In a stepwise logistical regression analysis smoking had
      a significant adjusted odds ratio for PAD of 4.29 (2.68 - 6.95), diabetes 1.72
      (1.11 - 2.69) and male sex 1.69 (1.06 - 2.68). Obesity as measured by BMI and
      hypertension were not associated with PAD. CONCLUSION AND RECOMMENDATIONS:
      Prevalence of PAD was relatively high in this sample of rural black patients when
      compared with findings from other countries. Preventive interventions should
      focus on control of diabetes and smoking cessation. Surprisingly, the prevalence
      was higher in those with a normal BMI and without hypertension, and risk factors
      in this community should be studied further. Physicians in this setting should be
      more aware of the possibility of undetected PAD.

PMID- 17446955
TI  - Can the outcome of induction of labour with oral misoprostol be predicted.
AB  - OBJECTIVE: To determine predictors of outcome for induction of labour using oral
      misoprostol. SETTING: Labour ward at Kalafong Hospital in Atteridgeville,
      Pretoria, that serves an indigent South African urban population. METHODS: Data
      were collected prospectively on all women undergoing induction of labour with
      oral misoprostol from 1 March 2004 to 28 February 2005. Patients with
      contraindications to misoprostol induction were excluded. Univariate analysis and
      logistical regression analysis were performed to determine the significant
      predictors of success of induction of labour. Successful induction was defined as
      a vaginal delivery achieved within 24 hours. RESULTS: Five hundred and fifty
      eight patients were included. There were three major indications for induction of
      labour, namely hypertension (45%), postdates (22.1%) and prelabour rupture of
      membranes (20.6%). Vaginal delivery was achieved within 24 hours in 52.4% of
      patients. The caesarean section rate was 42.1%. Fetal heart rate changes occurred
      in 25.6% and hyperstimulation in 1.4% of patients. Logistical regression analysis
      identified the following parameters as independent predictors of vaginal delivery
      achieved within 24 hours: primiparity (p < 0.001), Bishop score < 3 (p < 0.001),
      Bishop score 4 - 6 (p = 0.029), ruptured membranes (p < 0.001) and pre-eclampsia
      (p = 0.006). A method of scoring (Mbele score) has been developed making use of
      the results of this analysis in order to predict the successful outcome of
      induction. CONCLUSIONS: Primigravidity, intact membranes, pre-eclampsia and a low
      Bishop score were indicators of an unsuccessful outcome for induction of labour.
      It is thought that the Mbele score will be helpful in counselling patients on
      methods of delivery when they are admitted for induction of labour.

PMID- 17446956
TI  - Glycophorin A is recognized by an antibody population of the rabbit polyclonal
      antibodies produced against Citrobacter braakii O37.
AB  - BACKGROUND AND PURPOSE: Molecular mimicry was found in the case of Citrobacter
      braakii O37, which shares epitopes with human erythrocytes. It is believed that
      erythrocyte-membrane proteins band 3 and glycophorin A (GPA) have common
      epitopes. Band 3 was recognized by the anti-C. braakii O37 lipopolysaccharide
      antibodies (LPS-Abs) purified on LPS-affinity columns. This study aimed to
      investigate the role of GPA in this molecular mimicry. METHODS: Immunochemical
      methods such as immunoblotting, enzyme-linked immunosorbent assay, inhibition of
      hemagglutination, and affinity columns were employed. RESULTS: GPA when
      immobilized in an affinity column could purify specific GPA antibodies (GPA-Abs)
      from whole anti-C. braakii O37 serum. The purified antibodies, in turn,
      recognized GPA in immunoblotting tests. Treatment of human erythrocytes with
      sialidase significantly improved the hemagglutination titer by GPA-Abs.
      Furthermore, hemagglutination was inhibited to a greater extent by asialo-GPA
      than by the native form. GPA from blood groups M and N could similarly inhibit
      hemagglutination, and the most significant inhibition was recorded by GPA from
      the blood group MN. GPA-Abs could not recognize the LPS from C. braakii O37.
      CONCLUSIONS: Results confirmed that an antibody population in the anti-C. braakii
      O37 serum recognized GPA. However, there was no reactivity with LPS of C. braakii
      O37, indicating that the antibodies may be produced against the outer membrane
      protein of the bacteria.

PMID- 17446957
TI  - Presence and significance of transfusion-transmitted virus infection in Iranian
      patients on maintenance hemodialysis.
AB  - BACKGROUND AND PURPOSE: Transfusion-transmitted virus (TTV), a recently
      discovered DNA virus, was first identified in patients with non-A to -G hepatitis
      following blood transfusion. Transmission is generally via the parenteral route
      but recent data suggest that TTV can also be transmitted by the fecal-oral route.
      METHODS: This cross-sectional study was conducted in March 2005 and included 324
      patients on maintenance hemodialysis (HD) at 3 different centers in Tabriz, Iran.
      Demographic and clinical data were recorded. Blood samples for virological and
      biochemical tests were drawn simultaneously. TTV DNA was detected using semi
      nested polymerase chain reaction. Serum levels of alanine aminotransferase (ALT)
      and aspartate aminotransferase were also measured. RESULTS: Overall
      seroprevalence of TTV was 9.3% (95% confidence interval, 6.1-12.5%). Prevalence
      rates of hepatitis B surface antigen, hepatitis C virus antibody, and hepatitis E
      virus antibody were 4.6% (15/324), 20.4% (66/324), and 7.4% (24/324),
      respectively. Patients were negative for human immunodeficiency virus antibody.
      There was no association between TTV infection and elevated ALT levels. TTV
      positive patients were significantly younger than TTV-negative patients
      (p=0.018). There was no significant association between TTV positivity and age,
      gender, duration of HD, positivity for hepatitis B, C, or E virus infection
      markers, and history of transfusion and transplantation. CONCLUSION: We observed
      low TTV prevalence and no association between TTV and blood-borne infections in
      our HD patients. TTV infection was not related to elevated levels of liver
      enzymes; however, the clinical impact of this virus need further investigations.

PMID- 17446958
TI  - Survey of the status of self-paid varicella vaccination among children one to six
      years of age in Taiwan.
AB  - BACKGROUND AND PURPOSE: Prior to 2004, the mass immunization program in Taiwan
      did not include varicella vaccine; however, parents could have their children
      vaccinated by the self-payment option. METHODS: In April 2002, we distributed
      1271 questionnaires to the caregivers of children aged 1 to 6 years in Taoyuan
      county, Taiwan, to survey the status of vaccination rate against varicella,
      parental attitudes toward self-paid varicella vaccine, and the demographic
      characteristics of the family. RESULTS: Based on the answers provided in the
      questionnaires (99% response rate), we learned that until April 2002, the
      vaccination rate against varicella was 26%. Most children received this vaccine
      by the age of 1 to 2 years (64%) mainly at local clinics (66%). Majority of the
      caregivers (94%) would have immunized their children against varicella if the
      vaccines were freely provided or partially paid for. Caregivers living in the
      city, those children whose parents had a relatively high education level, those
      from families with fewer children, those whose children were inoculated with
      other self-paid vaccines, and those parents with a higher family income were
      significantly (p<0.0001) willing to have their children inoculated. CONCLUSIONS:
      In Taiwan, most caregivers were willing to have their children immunized against
      varicella if the vaccines were freely provided, or even if they were partially
      paid for. In case of other effective vaccines of high cost and not included in
      mass immunization, partially paying for the vaccine may be an option, since the
      parents' willingness was substantially greater when the cost is lowered.

PMID- 17446959
TI  - Coinfection and clinical manifestations of tuberculosis in human immunodeficiency
      virus-infected and -uninfected adults at a teaching hospital, northwest Ethiopia.
AB  - BACKGROUND AND PURPOSE: The pattern of clinical presentations of tuberculosis
      (TB) is reflected in the microbiological, radiological, and histological
      characteristics of the disease. However, coinfection with human immunodeficiency
      virus (HIV) poses special diagnostic and therapeutic challenges. This study was
      aimed at assessing the clinical manifestations of TB in patients with or without
      HIV coinfection in a hospital-based cross-sectional study in Gondar, Ethiopia.
      METHODS: TB was diagnosed following standard clinical, bacteriological,
      radiological, and histological procedures. HIV serostatus was checked by enzyme
      linked immunosorbent assay. RESULTS: This study included 257 TB patients, of whom
      52.1% were coinfected with HIV. Pulmonary TB and extrapulmonary TB were diagnosed
      in 64.2% and 35.8% of the patients, respectively. No significant association was
      found between sputum smear positivity and HIV serostatus. One-fifth of the
      patients reported hemoptysis. More than one-third had chest pain, and >90%
      reported fever and weight loss. Night sweats and cough were reported by 86% and
      82.5%, respectively. Coarse crepitations were the most frequent auscultatory
      finding (33.9%). Sputum smear positivity rate was 26.8%. Cavitation was
      significantly associated with sputum smear positivity (odds ratio = 9.0, 95%
      confidence interval = 2.4-34.1). Wasting, cough of <or=5 months' duration,
      crepitation, chronic diarrhea, and herpes zoster scar were significantly
      associated with HIV-positive serology. CONCLUSION: Coinfection with HIV was very
      high in patients with TB. The presence of herpes zoster scar, chronic diarrhea,
      coarse crepitations, and cough of <or=5 months' duration may assist in
      identifying TB patients with HIV infection.

PMID- 17446960
TI  - Synergistic antimicrobial effect of cefotaxime and minocycline on proinflammatory
      cytokine levels in a murine model of Vibrio vulnificus infection.
AB  - BACKGROUND AND PURPOSE: Vibrio vulnificus causes primary bacteremia and
      necrotizing wound infection, leading to high morbidity and mortality in humans.
      This study aimed to evaluate the antimicrobial effect of cefotaxime and
      minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus
      infection. METHODS: We investigated the dynamics of proinflammatory cytokines and
      their modulation by antimicrobial agents using a murine model of V. vulnificus
      infection. The change in cytokine levels was followed over a time course to
      identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c
      female mice were challenged with an intraperitoneal infection using a clinical
      invasive isolate of Vv05191, and their cytokine levels were assayed over various
      time points. RESULTS: Serum levels of tumor necrosis factor-alpha, interleukin
      (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and
      positively correlated to the subsequent fatality rate in the infected mice. With
      an inoculum of 6.6 x 10(6) colony-forming units and intraperitoneal
      administration of cefotaxime, minocycline, or both, the serum and peritoneal
      fluid cytokine levels increased and then declined gradually. Comparison of the 3
      antimicrobial regimens revealed that the magnitude of reduction in cytokine
      levels was greatest in mice treated with cefotaxime-minocycline combination.
      Moreover, the peritoneal fluid cytokine level in the combination group was
      significantly lower than that in the groups treated with minocycline or
      cefotaxime alone. CONCLUSIONS: The current results support the superiority of the
      combination therapy in treating invasive V. vulnificus infections.

PMID- 17446961
TI  - Comparison of in vitro activities of levofloxacin, ciprofloxacin, ceftazidime,
      cefepime, imipenem, and piperacillin-tazobactam against aerobic bacterial
      pathogens from patients with nosocomial infections.
AB  - BACKGROUND AND PURPOSE: There is a rapid worldwide emergence of multidrug
      resistant pathogens, especially in nosocomial isolates. This study compared the
      in vitro activities of levofloxacin, ciprofloxacin, ceftazidime, cefepime,
      imipenem, and piperacillin-tazobactam against 208 aerobic bacterial pathogens
      that caused 197 nosocomial infections in 184 patients. METHODS: Antimicrobial
      susceptibility was evaluated by E test in accordance with the guidelines of the
      National Committee for Clinical Laboratory Standards. RESULTS: Most (140/208,
      67%) of the isolates were facultative Gram-negative bacilli. Levofloxacin and
      ciprofloxacin were the most effective (22/22, 100%) against oxacillin-sensitive
      Staphylococcus aureus. None of the antibiotics tested were found to be effective
      (0/25) against oxacillin-resistant S. aureus. Of the 11 isolates of Acinetobacter
      baumannii that were not pandrug-resistant (PDR), only 9 isolates (9/11, 81%) were
      sensitive to imipenem and 5 isolates (5/11, 45%) were sensitive to levofloxacin,
      ciprofloxacin, and ceftazidime. Another 22 isolates of A. baumannii that were PDR
      were completely resistant to all 6 antibiotics. The majority of isolates of
      Pseudomonas aeruginosa were sensitive to these 6 antimicrobial agents with 10/11
      (91%) sensitive to levofloxacin and ciprofloxacin, 9/11 (83%) sensitive to
      ceftazidime, cefepime and piperacillin-tazobactam, and 8/11 (75%) sensitive to
      imipenem. CONCLUSIONS: The majority of the bacterial isolates causing nosocomial
      infections were found to be sensitive to the 6 antibiotics tested. Bacterial
      isolates of nosocomial infections that were completely resistant to these 6
      antibiotics were PDR A. baumannii, PDR P. aeruginosa, and oxacillin-resistant S.
      aureus. More potent antimicrobial agents are needed to treat infections caused by
      PDR A. baumannii and PDR P. aeruginosa.

PMID- 17446962
TI  - Invasive pulmonary aspergillosis: high incidence of disseminated intravascular
      coagulation in fatal cases.
AB  - BACKGROUND AND PURPOSE: Disseminated intravascular coagulation (DIC) is a rarely
      described finding in invasive pulmonary aspergillosis (IPA) with unclear impact
      on mortality. METHODS: This study included patients with positive cultures of
      Aspergillus spp. from respiratory specimens, serological evidence of
      aspergillosis, or lung biopsy findings supporting aspergillosis treated at
      National Taiwan University Hospital from January 1999 to June 2005. IPA was
      defined based on the consensus of the European Organization for Research and
      Treatment of Cancer, and the Mycosis Study Group of the National Institute of
      Allergy and Infectious Diseases. Univariate logistic regression analysis was used
      to evaluate the factors associated with mortality. RESULTS: Proven or probable
      IPA was diagnosed in 26 patients. Hematological malignancy was found in 11
      patients (42%) and immunosuppressive agents had been administered to 17 patients
      (65%). Among 20 culture-proven infections (77%), the most frequently encountered
      fungi were Aspergillus fumigatus (46%) and Aspergillus flavus (23%). The overall
      mortality rate was 62%. Univariate and multivariate analyses revealed that DIC
      was the only factor that was significantly associated with death attributable to
      IPA (p<0.01). CONCLUSIONS: IPA is associated with a high mortality rate,
      particularly for patients with DIC.

PMID- 17446963
TI  - Assessment of Platelia Aspergillus enzyme immunoassay for the diagnosis of
      invasive aspergillosis.
AB  - BACKGROUND AND PURPOSE: This study investigated the diagnostic value of Platelia
      Aspergillus enzyme immunoassay (EIA) for galactomannan (GM) antigen in patients
      at risk of invasive aspergillosis (IA), and its association with clinical course
      and outcome. METHODS: A total of 304 blood samples were collected from 189
      patients at risk of IA during a 1-year period at a tertiary referral center.
      Classification of IA was made on the basis of the European Organization for
      Research and Treatment of Cancer case definitions. RESULTS: Of the 189 patients,
      5 had proven IA, 9 had probable IA, 26 had possible IA, and 149 had no IA.
      Diagnostic levels of GM were detected in 80% of proven and in 77% of probable IA
      cases. The overall sensitivity, specificity, and positive and negative predictive
      values for this assay, using a 1.5 index cut-off value, were 78.6%, 93.9%, 55.0%,
      and 97.9%, respectively. With the 0.5 index cut-off value, the sensitivity would
      increase to 100%. A close relationship was found between clinical course and the
      kinetics of GM indices in survivors. CONCLUSIONS: The Platelia Aspergillus EIA is
      a useful screening test for the detection of IA. Regular monitoring of the
      kinetics of GM-EIA indices is a useful predictor of clinical course and outcome.

PMID- 17446964
TI  - Cryptosporidiosis among immunocompetent patients with gastroenteritis in Iran: a
      comparison with other enteropathogenic parasites.
AB  - BACKGROUND AND PURPOSE: Cryptosporidium is a protozoan parasite that reproduces
      within the epithelial cells of several organs of vertebrate hosts. The
      manifestation of the disease is either self-limiting acute diarrhea in
      immunocompetent patients, or fatal chronic diarrhea in immunocompromised
      patients. Common clinical symptoms include watery diarrhea, abdominal pain, and
      weight loss. METHODS: This randomized pilot study conducted in Tehran, Iran,
      included 104 children and adult patients with gastroenteritis referred to the
      Children's Hospital Centre and Pasteur Institute of Iran. Control samples from
      healthy individuals (36 children and adults) were also collected; the entire test
      group had diarrhea and the control group had formed stool consistency. Stool
      samples were primarily examined by the direct method, then fixed and tested by 3
      assays including acid-fast staining, auramine phenol fluorescence, and direct
      fluorescence using monoclonal antibody. RESULTS: The study revealed that 2.9% of
      the patients were infected by Cryptosporidium spp. Other parasites observed
      included Giardia lamblia (5.8%), Ascaris lumbricoides (1.9%), and Entamoeba
      histolytica (0.96%). Formed stool samples showed no oocysts of Cryptosporidia.
      CONCLUSIONS: In addition to common enteropathogenic organisms, Cryptosporidium is
      indicated as a key causative agent of diarrhea in humans. Although
      cryptosporidiosis may, in many cases, be terminated by self-limiting mechanisms,
      it could cause pathologies requiring preventive and therapeutic policies.

PMID- 17446965
TI  - Microbiological features of persistent nonspecific urethritis in men.
AB  - BACKGROUND AND PURPOSE: The role of opportunistic microorganisms in urethritis in
      men is controversial. The aim of this study was to determine the changes in
      urethral microflora in the presence of persistent nonspecific urethritis (PNU) in
      men by in vitro detection of decomplementary activity (DCA) phenotypes of
      urethral isolates and comparison of the isolates with those from patients with or
      without PNU. METHODS: The study included 18 healthy men and 24 men with PNU.
      Culture specimens were spread on various selective media. Bacterial DCA was
      tested by measuring the decrease in complement activity (CH(50)) under the
      influence of culture supernatants. RESULTS: The most common isolates in both
      groups were coryneforms, coagulase-negative staphylococci, and streptococci.
      Enterobacteriaceae, enterococci, micrococci, and Staphylococcus aureus were
      isolated only from the PNU group. Simpson's diversity index (D) was significantly
      lower in the PNU group as compared to that in healthy men (D = 1.37 +/- 0.4
      versus 3.5 +/- 0.9, p<0.05). DCA of staphylococci from the PNU group was
      significantly higher than that of the control group (7.3 +/- 1.4 versus 1.56 +/-
      1.05 anti-CH(50), p<0.05). DCAs of Enterobacteriaceae and enterococci were 16.7
      +/- 0.5 and 7.2 +/- 2.9 anti-CH(50), respectively, while that of micrococci was
      7.4 +/- 3.2 anti-CH(50). CONCLUSIONS: PNU is associated with a decrease in
      bacterial diversity and the occurrence of opportunistic microorganisms with
      pronounced pathogenic properties in the urethral microflora. These data suggest
      that PNU may be associated with microecological disorders.

PMID- 17446966
TI  - Changes in serum eotaxin and eosinophil cationic protein levels, and eosinophil
      count during treatment of childhood asthma.
AB  - BACKGROUND AND PURPOSE: Increased serum levels of eotaxin are related to the
      severity of asthma in adults. There are limited data on the effects of oral
      corticosteroids and inhaled corticosteroid therapy on serum levels of eotaxin and
      eosinophil cationic protein (ECP) and peripheral blood eosinophil counts (ECs) in
      pediatric asthma patients. We investigated prospectively the changes in eotaxin
      and ECP serum levels and peripheral blood ECs after administering oral
      corticosteroids and then inhaled corticosteroids plus long-acting beta2 agonist
      treatment in pediatric patients. METHODS: Serum samples of 20 pediatric patients
      with mild-to-moderate asthma were collected before treatment, after 5-7 days of
      oral prednisolone treatment, and after 1-2 months of inhaled fluticasone plus
      salmeterol treatment. Peak expiratory flow was used as the outcome index.
      RESULTS: Serum eotaxin levels remained the same after oral prednisolone
      treatment, but decreased after subsequent inhalation treatment compared with the
      end of oral steroid treatment (64.7 +/- 22.6 vs 85.7 +/- 36.8 pg/mL, p<0.001).
      The EC and serum ECP levels declined soon after oral steroid treatment,
      rebounding to initial levels during inhalation treatment. The decrease in ECP
      level was positively correlated with the decrease in ECs with oral steroid
      treatment (r(2) = 0.28, p=0.016). There was no correlation between changes in
      eotaxin levels and peak expiratory flow. CONCLUSIONS: Our data suggest that the
      serum eotaxin level, not peripheral blood EC or serum ECP level, declines during
      inhaled fluticasone plus salmeterol treatment and might serve as a surrogate
      marker of T helper 2 residual activity in pediatric asthma.

PMID- 17446967
TI  - Plasma soluble CD30 level correlates negatively with age in children.
AB  - BACKGROUND AND PURPOSE: Atopic diseases are thought to be associated with
      cytokine-mediated immune dysregulation, for example, a T helper cell type 1/2
      (Th1/Th2) imbalance. CD30 is proposed to be one of the surrogate markers for Th2
      immunity. In this study, we investigated whether CD30 is a good marker for atopy
      and Th2 predominance in a pediatric population. METHODS: This study included 61
      children with atopy and 27 normal controls. The expression of CD30 on the surface
      of T and B lymphocytes and soluble CD30 (sCD30) in plasma was determined.
      RESULTS: There was no difference in the surface expression of CD30 on B or T
      lymphocytes. Similarly, sCD30 levels in plasma were not different between the 2
      groups. Nevertheless, we found a strong negative correlation between sCD30 and
      age in the control group (r = -0.72, p<0.001; sCD30 = 76.1 - 5.18 x age) as well
      as in the atopy group (r = -0.45, p<0.01; sCD30 = 61.1 - 3.56 x age).
      CONCLUSIONS: An inverse relationship was found between age and sCD30 level in
      children. However, our findings suggest that CD30 is not a good marker for atopic
      disease and that further studies on sCD30 levels must take age into
      consideration.

PMID- 17446968
TI  - Epstein-Barr virus-associated smooth muscle tumor in patients with acquired
      immunodeficiency syndrome.
AB  - Epstein-Barr virus (EBV)-associated smooth muscle tumor (SMT) is a recognized but
      uncommon disease that is found to occur in patients with immunocompromised
      conditions such as acquired immunodeficiency syndrome (AIDS). These tumors may be
      multifocal and located at unusual sites, such as the brain and liver. This report
      describes the case of 2 AIDS patients with EBV-associated SMT and highlights the
      features and outcome of this rare but potentially important tumor in human
      immunodeficiency virus management.

PMID- 17446969
TI  - Melioidotic septic arthritis: a case report and literature review.
AB  - Burkholderia pseudomallei, the causative agent of melioidosis, is endemic in
      southeast Asia and northern Australia. In recent years, the incidence of
      melioidosis has increased worldwide. Septic arthritis is a rare but well
      recognized manifestation of melioidosis. Patients with underlying medical
      conditions, such as diabetes mellitus, renal impairment, cirrhosis, and
      malignancy are at greater risk. The presentations of melioidotic septic arthritis
      often mimic other disease processes and patients may not always be clinically
      septic. We present a case of septic arthritis due to B. pseudomallei in a 66-year
      old male with diabetes mellitus presenting with a history of fever and ankle
      swelling. Follow-up ankle X-ray showed soft tissue swelling. Synovial fluid and
      blood samples grew B. pseudomallei. The patient improved gradually after
      parenteral administration of ceftazidime (2 g 8-hourly) and cotrimoxazole (1440
      mg 8-hourly). He was discharged on oral cotrimoxazole (1440 mg 12-hourly),
      doxycycline (100 mg 12-hourly), and chloramphenicol (500 mg 6-hourly) for 6
      months. This case highlights the possible occurrence of melioidotic septic
      arthritis, and the importance of prompt initiation of appropriate antimicrobials
      to achieve good outcomes.

PMID- 17446970
TI  - Long-term effects of child abuse and neglect on alcohol use and excessive
      drinking in middle adulthood.
AB  - OBJECTIVE: The purpose of this study was to determine the long-term effects of
      child abuse and neglect on alcohol use in middle adulthood. METHOD: Individuals
      with documented cases of childhood physical and sexual abuse and/or neglect (n =
      500) and matched controls (n = 396) from a metropolitan county in the Midwest
      were followed and interviewed in middle adulthood. Outcomes were Diagnostic and
      Statistical Manual of Mental Disorders, Third Edition, Revised, diagnoses of
      alcohol abuse or dependence in young adulthood (age 29) and excessive drinking in
      middle adulthood (age 40). RESULTS: Women with documented histories of child
      abuse or neglect reported higher past-year typical quantity (p < .01) and past
      month number of days drinking eight or more drinks (p < .05) than
      nonabused/nonneglected women. Controlling for parental alcohol/drug problems, the
      effect of child maltreatment on excessive drinking in middle adulthood was not
      significant for women. For women, the final structural equation model revealed an
      indirect path through alcohol diagnosis in young adulthood (p < .05) to excessive
      drinking in middle adulthood (p < .001) but no direct path from child abuse and
      neglect to excessive drinking in middle adulthood. For men, there were no
      significant paths from child abuse and neglect to alcohol diagnosis in young
      adulthood or excessive drinking in middle adulthood. For men and women, parental
      alcohol/drug problems had a significant indirect effect on the offspring's
      drinking in middle adulthood (p < .001) through young adult alcohol diagnosis (p
      < .001). CONCLUSIONS: Consequences of abuse and neglect persist into middle
      adulthood for women, through continuation of earlier alcohol problems, suggesting
      the need for interventions throughout the life course. The influence of parental
      alcohol and drug problems warrants further attention.

PMID- 17446971
TI  - Alcohol use and protective sexual behaviors among high-risk adolescents.
AB  - OBJECTIVE: This study seeks to advance our understanding of moderating influences
      on the relationship between alcohol and condom use by examining their association
      at both the global and event levels of analysis using a prospective approach
      within a sample of high-risk adolescents. The following potential moderators were
      examined: sex-related alcohol expectancies, gender, relationship type, level of
      alcohol use, and impulsive sensation seeking. METHOD: Criminally involved
      adolescents (N = 300) completed measures of alcohol use, condom use, personality,
      and alcohol expectancies; 267 (89%) participants completed a behavioral
      assessment 6 months later. RESULTS: At the global level of analysis, there was a
      significant moderating effect of alcohol-related sexual-enhancement expectancies,
      such that the relationship between alcohol and condom use was negative and
      significant only among individuals with higher sexual-enhancement expectancies.
      At the time-limited global level, impulsive sensation seeking at baseline was
      negatively associated with condom use at 6-month follow-up. At the event level,
      there was a Gender x Alcohol interaction such that alcohol use was unrelated to
      condom use among males but was strongly and negatively related among females.
      CONCLUSIONS: This study makes a contribution to the understanding of the
      relationship between alcohol use and condom use by looking beyond main effects
      and conducting an empirically driven and multilevel examination of moderating
      variables. Results support the inclusion of situation-specific alcohol risk
      reduction content in human immunodeficiency virus/sexually transmitted disease
      prevention activities.

PMID- 17446972
TI  - Military culture and drinking behavior among U.S. Navy careerists.
AB  - OBJECTIVE: This study builds on research linking work culture and drinking
      behavior to examine the influence of the military work environment, especially
      deployment and liberty, on heavy and heavy episodic drinking among career
      enlistees and officers. METHOD: Both quantitative (self-administered cross
      sectional survey data collected from 2,380 respondents) and qualitative (home
      base and shipboard observations and ethnographic interviews with 81 enlisted and
      officer personnel) methods provided data. Linear regression analyses were used to
      examine the relationship between occupational factors (enforcement of alcohol
      policy, work problems, work-related stress, and length of deployment) and
      positive normative beliefs for heavy drinking during deployment liberty. Logistic
      regression analyses were used to examine the relationship between positive
      normative beliefs and four drinking-related outcomes (past 12-month Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV], alcohol
      abuse and frequent heavy drinking, and heavy drinking and heavy episodic drinking
      during most recent deployment liberty). RESULTS: Occupational factors were
      significantly related to positive normative beliefs for heavy drinking during
      deployment liberty; in turn, positive normative beliefs were significantly
      associated with each drinking outcome. Although the prevalence of DSM-IV alcohol
      abuse differed significantly between men and women (28.2% vs 15.1%), as did the
      prevalence for frequent heavy drinking (13.7% vs 8.9%), no gender differences
      were found in the prevalence of heavy episodic drinking or heavy drinking during
      the most recent deployment liberty. Ethnographic results provided descriptions of
      the cultural context of drinking behavior in relation to ambivalent alcohol
      policy, relief from work-related stress, ritual of free-range behavior on
      deployment liberty, and long-standing traditions. CONCLUSIONS: Prevention
      measures in the military may require policy and environmental changes.

PMID- 17446973
TI  - Alcohol-caused mortality in australia and Canada: scenario analyses using
      different assumptions about cardiac benefit.
AB  - OBJECTIVE: The purpose of this study was to examine how definitions of
      "abstainers" in prospective studies of alcohol and mortality influence estimates
      of the extent of coronary heart disease (CHD) protection due to low-risk alcohol
      consumption. METHOD: Meta-analyses were conducted on 35 prospective studies
      categorized according to the presence of up to two postulated errors for men and
      women regarding the classification of abstainers. Risk of death from CHD was
      estimated to calculate age-gender specific etiological fractions for application
      to mortality data for Australia and Canada in 2002. Controls for study
      characteristics were age, history of illness, and smoking status. Abstainers were
      classified as (1) lifelong abstainers, exdrinkers, and occasional drinkers--both
      classification errors present; (2) lifelong abstainers and exdrinkers--one error;
      and (3) lifelong abstainers only. "Low-risk consumption" was defined as up to 24
      g, on average, per day for women and 44 g for men; "elevated risk consumption"
      was defined as more than 24 g on an average day for women and more than 44 g for
      men. Higher daily alcohol consumption was classified as "high risk." RESULTS:
      Significant CHD protection was found for both men (odds ratio [OR] = .79) and
      women (OR = .89) only in studies committing both errors; it was found for women
      only in studies with "occasional drinker" error (OR = .75) and for neither gender
      in the few available error-free studies. Estimates of net alcohol-caused deaths
      in 2002 varied accordingly, from -1,405 to 2,479 for Australia and from 4,321 to
      7,319 for Canada. CONCLUSIONS: There is a need for CHD mortality studies that use
      lifelong abstinence as the reference point for estimating CHD protection. There
      may be gender differences in CHD protection. Separate estimates for the effects
      of low- and elevated-risk alcohol consumption on mortality should be made and
      communicated.

PMID- 17446974
TI  - Six-month treatment outcomes of cocaine-dependent patients with and without PTSD
      in a multisite national trial.
AB  - OBJECTIVE: This study examined 6-month treatment outcomes among 428 cocaine
      dependent outpatients with (n = 34) and without (n = 394) posttraumatic stress
      disorder (PTSD) in a randomized controlled multisite clinical trial of manual
      based psychotherapies for substance use disorder (SUD). METHOD: Assessments were
      completed at baseline and monthly during the 6-month treatment. With longitudinal
      mixed-effects models, we compared outcomes between SUD-PTSD and SUD-only patients
      and also examined rates of within-group change. RESULTS: Results indicated a
      highly consistent pattern: the SUD-PTSD patients were more impaired to begin with
      and remained so across time compared with SUD-only patients (with the exception
      of substance use and addiction-related legal and employment problems, which did
      not differ between groups). Also, the SUD-PTSD patients improved less than SUD
      only patients in alcohol use and the majority of addiction-related psychosocial
      problems. However, the two groups did not differ significantly in improvement
      over time on drug use or global psychological severity. CONCLUSIONS: The greater
      impairment and relative lack of improvement of SUD-PTSD patients, compared with
      those with SUD-only, suggest a need for dual-diagnosis treatments that more
      directly target their areas of difficulty.

PMID- 17446976
TI  - The ability of the Self-Rating of the Effects of Alcohol (SRE) Scale to predict
      alcohol-related outcomes five years later.
AB  - OBJECTIVE: A low level of response (LR) to alcohol as measured through alcohol
      challenges is an early-appearing, genetically influenced characteristic that
      predicts the risk of heavier drinking and alcohol problems. A less expensive and
      more easily used measure of LR, the retrospective Self-Rating of the Effects of
      Alcohol (SRE) questionnaire, also relates to alcohol intake and problems but has
      not been evaluated for its ability to predict alcohol-related problems 5 years
      later. METHOD: At Time 1, 95 18- to 35-year-old (mean age: 25.9 years) subjects
      who were offspring from families participating at the San Diego site of the
      Collaborative Study on the Genetics of Alcoholism (COGA) were administered the
      SRE and evaluated regarding alcohol, drug, and demographic characteristics using
      the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) interview.
      Follow-up interviews (Time 2) using the SSAGA were completed an average (SD) of
      5.4 (1.34) years later for approximately 80% of the original sample. RESULTS: The
      retrospective SRE score at Time 1 (the number of drinks for effects the first
      five times [First 5] of drinking) correlated with Time 2 maximum quantity and
      frequency, alcohol problems overall, the number of alcohol-dependence items
      endorsed, and the Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, diagnosis of alcohol abuse or dependence. The relationships remained
      robust in hierarchical logistic regression analyses even in the context of age,
      gender, the number of SRE items endorsed, and alcohol use and problem variables
      at Time 1. The regressions explained between 21% and 43% of the variance of the
      outcomes overall, with the First 5 SRE score alone accounting for between 4% and
      14%. CONCLUSIONS: These findings are consistent with the ability of SRE-based LR
      scores at Time 1 to predict alcohol-related outcomes over the subsequent 5 years.

PMID- 17446977
TI  - The relationship between prospective self-rating of alcohol sensitivity and
      craving and experimental results from two alcohol challenge studies.
AB  - OBJECTIVE: Determining whether individuals can provide accurate reports of
      alcohol sensitivity and craving, outside of a laboratory alcohol challenge, has
      important research and clinical implications. The primary goals of the present
      study are (1) to test the relationship between prospective self-ratings of the
      effects of alcohol and alcohol craving, and experimental results from alcohol
      challenge studies and (2) to examine potential moderators of that relationship.
      METHOD: Participants were heavy drinkers who completed either an intravenous (n =
      49) or an oral administration (n = 135) alcohol challenge. Participants were
      asked to estimate their craving for alcohol in a drinking situation and their
      subjective intoxication after consuming three drinks. Subjective intoxication and
      alcohol craving were then assessed during the laboratory alcohol challenge.
      RESULTS: Estimated subjective intoxication and alcohol craving were significant
      predictors of subjective intoxication and craving measured under laboratory
      conditions and accounted for, at most, 16% and 37%, respectively, of the variance
      in laboratory measures. CONCLUSIONS: Taken together, these findings suggest that
      sensitivity to the effects of alcohol and alcohol craving may be measured outside
      of the laboratory but that scales that are especially designed for nonlaboratory
      studies may be required.

PMID- 17446975
TI  - Between- and within-family association test of the dopamine receptor D2 TaqIA
      polymorphism and alcohol abuse and dependence in a general population sample of
      adults.
AB  - OBJECTIVE: Dopaminergic dysfunction has been hypothesized to play an important
      role in the etiology of alcohol-use disorders. A restriction fragment length
      polymorphism (RFLP) in the 3' untranslated region (3'UTR) of the DRD2 gene
      affects gene expression and has been implicated as a risk factor for alcohol
      dependence. This polymorphism (TaqIA) has been reported as positively associated
      with alcohol-use disorders in case-control samples, but these results have not
      been replicated in family-based association studies. The mixed results of
      association between the DRD2 TaqIA polymorphism and alcohol-use disorders may be
      the result of differences in sample size, phenotype definition, heterogeneity of
      the samples, and genetic admixture. METHOD: We conducted tests of association in
      a sample of 838 adults participating in the National Youth Survey Family Study
      (NYSFS). We examined whether the DRD2 TaqIA polymorphism was associated with a
      symptom-count measure of alcohol abuse and dependence derived from the Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition, and the Craving
      Withdrawal Model. RESULTS: Tests of association were nonsignificant across each
      classification system examined. Power calculations suggested that these results
      were despite the ability to detect an effect size of 1%. CONCLUSIONS: This study
      supports other family-based association tests that have reported no association
      between the DRD2 TaqIA polymorphism and alcohol abuse and dependence.

PMID- 17446978
TI  - Normative beliefs, misperceptions, and heavy episodic drinking in a british
      student sample.
AB  - OBJECTIVE: Numerous studies have demonstrated the existence and effect of
      normative misperceptions on heavy episodic drinking behavior. However, there has
      been little work on these processes or application of normative-belief
      interventions outside the U.S. college system. The aim of the current study,
      therefore, was to investigate heavy episodic drinking and normative
      misperceptions in a U.K. university setting. METHOD: An email containing a link
      to a survey Web site was distributed to all current undergraduate students at the
      University of Paisley, Scotland. In addition to age and gender questions, the
      survey contained items on students' personal behavior and perception of the level
      of that behavior in three groups of increasing social distance: close friends,
      other students of the same age, and other people of the same age in U.K. society
      in general. RESULTS: Completed surveys from 500 respondents were returned. In
      keeping with previous research, significant correlations were found between the
      respondents' behavior and the perception of that behavior in others, with beliefs
      about the most proximal individuals being the most strongly correlated. The
      majority of respondents were also found to overestimate alcohol consumption in
      other students. An age effect was noted, in which misperceptions appeared to
      decrease with age but did not vary between genders. CONCLUSIONS: The findings of
      the study indicate that the normative-belief alcohol consumption processes that
      have been found on U.S. college campuses also operate in U.K. university
      settings. This raises the possibility of applying social-norms interventions from
      the United States to the United Kingdom and potentially elsewhere in the world.
      Furthermore, the study noted apparent age effects in the degree of misperception,
      the implications of which are discussed.

PMID- 17446979
TI  - Reasons for drinking in the college student context: the differential role and
      risk of the social motivator.
AB  - OBJECTIVE: The present study examines the relationships among reasons for
      drinking, alcohol consumption, and alcohol-related consequences in two college
      aged samples. Personal motivators such as mood enhancement and coping (tension
      reduction) have consistently been shown to predict problematic alcohol use, but
      because of the salient nature of social drinking in college, we hypothesized that
      social reasons for drinking would be most frequently endorsed and, in turn,
      predict negative consequences. METHOD: T w o distinct samples--119 co-ed
      adjudicated students sanctioned by the university for violating campus alcohol
      policy and 106 co-ed volunteer students--completed measures assessing alcohol
      consumption, reasons for drinking, and consequences. Differential effects between
      genders were examined. RESULTS: Social camaraderie (SC) was the most frequently
      endorsed reason for drinking. Regression analyses controlling for previous
      drinking revealed that social reasons for drinking predicted alcohol-related
      problems among female students in both samples. Additionally, SC was
      significantly correlated with every drinking measure and problem measure at 1
      month for females in both the adjudicated and the volunteer groups. Total drinks,
      drinking days, and heavy episodic drinking events correlated with SC for males in
      the adjudicated sample. CONCLUSIONS: For females, these results suggest a
      relationship between social reasons for drinking and alcohol-related
      consequences, which previous research has not identified. More research is needed
      to explore females' reasons for drinking, accompanying problems, and the
      underlying psychosocial traits associated with these reasons.

PMID- 17446980
TI  - Alcohol risk-reduction skills training in a national fraternity: a randomized
      intervention trial with longitudinal intent-to-treat analysis.
AB  - OBJECTIVE: The potential effectiveness of two group-administered social-skills
      training interventions for reducing high-risk drinking behavior was evaluated
      through a prospective randomized intervention trial with 3,406 members of a
      national college fraternity. METHOD: Ninety eight of 99 chapters of a national
      fraternity were randomly assigned, within three strata, to receive (1) a 3-hour
      baseline intervention, (2) the same baseline intervention plus two booster
      sessions, or (3) assessments only. The current article emphasizes a rigorous
      intent-to-treat analysis model that compares outcomes among members assigned to
      receive study interventions (vs assessment-only sites) regardless of whether they
      actually did receive them; it also includes individuals at intervention sites
      even if they did not participate. This model allows us to address a social policy
      issue regarding the effect that introducing such an intervention may have in
      changing the high-risk normative drinking environment of the fraternity itself.
      RESULTS: Frequent heavy drinkers (64.2% of members) assigned to either
      intervention showed significant reductions at a 6-month follow-up in their
      frequency of drinking, heavy drinking, and drinking to intoxication; plus, they
      reported consuming fewer drinks overall. At 12 and 18 months postbaseline, these
      positive outcomes had largely dissipated. Additionally, there was an increase in
      drinking among lower-risk members 18 months postbaseline, which may be the result
      of factors other than differential attrition. CONCLUSIONS: Findings suggest that
      introducing such a brief intervention can effectively reduce risky drinking
      behavior on a short-term basis in high-risk members of a national fraternity.
      Future studies may wish to focus on strategies for sustaining positive outcomes
      for longer, plus would benefit, in general, from learning more about mechanisms
      of change.

PMID- 17446981
TI  - Attitudes and perceived approval of drinking as mediators of the relationship
      between the importance of religion and alcohol use.
AB  - OBJECTIVE: Previous research has consistently demonstrated that religiosity and
      personal importance of religion are associated with lower levels of alcohol use
      among both adolescents and college students. Although a number of different
      mechanisms have been proposed to account for this, few studies have empirically
      examined potential mediators of this relationship. Given the extensive literature
      on the impact of social norms on the drinking behavior of college students, the
      present study evaluates the role of perceived drinking norms as a mediator of the
      relationship between the importance of religion and alcohol use. Specifically, we
      examined both personal attitudes and perceived injunctive norms with regard to
      reference groups that vary in their proximity to students (i.e., close friends
      and typical college students). METHOD: Participants were 1,400 undergraduate
      students (60.6% women) who were assessed using self-report measures of alcohol
      consumption, importance of religion, attitudes, and perceived norms. RESULTS:
      Results indicated that, consistent with the hypotheses, personal attitudes were
      the strongest mediator of the relationship between importance of religion and
      alcohol use, followed by the approval of close friends, and, to a lesser extent,
      the approval of typical college students. CONCLUSIONS: These findings suggest
      that importance of religion may have an indirect effect on alcohol use via
      personal attitudes and the perceived approval or disapproval of important others,
      and this relationship varies as a function of reference group. Implications for
      interventions that incorporate information on social norms are discussed.

PMID- 17446982
TI  - Moderate drinking in the first year after treatment as a predictor of three-year
      outcomes.
AB  - OBJECTIVE: The relationship between moderate alcohol consumption in the first
      year following alcohol treatment admission and longer-term functioning is
      clinically important and pertains to the clinical course of alcohol-use
      disorders. This study investigated these relationships, focusing on the first
      year posttreatment admission and 3 years later. METHOD: Analyses were conducted
      on the outpatient Project MATCH (Matching Alcoholism Treatments to Client
      Heterogeneity) sample (n = 952 at baseline, and n = 802 at Months 37-39).
      Participants were classified as first-year "abstainer," "moderate drinker," or
      "heavy drinker." RESULTS: Drinker classification predicted percentage of days
      abstinent from alcohol, drinks per drinking day, and alcohol-related negative
      consequences at 3 years. The abstainers had better drinking outcomes than either
      of the other two groups, and the moderate drinkers' outcomes were better than
      those of the heavy drinkers. The heavy drinkers had a higher rate of negative
      consequences at 3 years than did the abstainers and the moderate drinkers, who
      did not differ from each other. Analyses of change in drinker status between 1
      and 3 years explored variability in clinical course. CONCLUSIONS: First-year
      posttreatment alcohol use on the group level predicts longer-term alcohol use and
      related functioning, and moderate drinking may be considered a treatment goal
      option for some individuals. The data also reaffirm the variability among
      individuals in clinical course following alcohol treatment. Future research
      should aim to understand the factors that determine the maintenance of patterns
      of alcohol use that are not associated with the occurrence of alcohol-related
      negative consequences.

PMID- 17446983
TI  - Relationship and institutional pressure to enter treatment: differences by
      demographics, problem severity, and motivation.
AB  - OBJECTIVE: Studies have shown that individuals with substance-use problems
      frequently receive pressure to enter treatment. Pressure can come from
      institutions (e.g., criminal justice or welfare) or relationships (e.g., family
      or friends). Research has also shown that pressure can facilitate treatment
      entry. However, few studies have assessed how pressure from different sources
      varies. METHOD: Six hundred ninety-eight individuals entering residential or
      outpatient treatment for alcohol or drug problems completed face-to-face
      interviews soon after admission. Pressure was assessed by asking participants if
      others had suggested they enter treatment, including family, friends, and
      professionals within institutions. Additional assessments included the Addiction
      Severity Index and readiness to change. RESULTS: Most of the participants (73%)
      reported some type of pressure: 29% from personal relationships, 30% from
      institutions, and 14% from both. The remaining 27% reported no pressure to enter
      treatment. Multinomial logistic regression of baseline data showed being on
      parole or probation, not being employed full time, and having more severe legal
      problems predicted pressure from institutions. In contrast, relationship pressure
      at baseline was predicted by severity of alcohol problems. Compared with
      participants receiving only relationship pressure, those receiving only
      institutional pressure had lower alcohol, drug, family, psychiatric, and medical
      severity. In addition, institutional pressure was associated with lower
      motivation at baseline, whereas relationship pressure was not related to
      motivation at all. When controlling for problem severity, baseline pressure was
      not associated with 12-month outcome. CONCLUSIONS: Correlates of pressure from
      institutions for individuals to enter treatment differ from those associated with
      pressure from personal relationships to enter treatment. Implications of these
      findings for public policy, treatment, and further research are discussed.

PMID- 17446984
TI  - Upward pressures on drinking: exposure and reactivity in adulthood.
AB  - OBJECTIVE: The purpose of this study was to identify the situations most commonly
      linked with increased drinking for different life periods and for nonproblem and
      problem drinkers. METHOD: A community sample of older adults (average age 69
      years; 42% women), consisting of 480 nonproblem and 351 problem drinkers,
      provided information about their life history of drinking. For each of three life
      periods (early adulthood, early middle age, and late middle age), respondents
      indicated whether they experienced particular situations (exposure) and, if so,
      whether they increased their alcohol consumption in response to these situations
      (reactivity). These situations included social influences and stressors. RESULTS:
      Exposure to social influences and to stressors varied across life periods, as did
      drinking reactivity. Overall, the social influences of having peers or a partner
      who drank and the stressors of family interpersonal problems and emotional
      distress were common experiences and also were among the most likely to be linked
      with increased alcohol consumption. Compared with nonproblem drinkers, problem
      drinkers reported significantly higher levels of exposure to social influences
      and to stressors and also were much more reactive to them. CONCLUSIONS:
      Prevention and treatment of alcohol use disorders can be tailored to take into
      account variations in exposure and reactivity to situations that may place upward
      pressure on drinking.

PMID- 17446985
TI  - Next-day effects of alcohol and an additional stressor on memory and psychomotor
      performance.
AB  - OBJECTIVE: This study aimed to investigate the effects of a stressor, white
      noise, on cognitive performance of subjects in the compromised hangover state.
      METHOD: The study followed a mixed factorial, counterbalanced, repeated-measures
      design with noise, order of testing, and time of testing as between-participants
      factors and state during testing as a within-participants factor. Seventy-eight
      participants performed memory and psychomotor tasks the morning after a regular
      night of drinking and the morning after a night of no alcohol consumption. Forty
      eight participants were tested in the no-noise condition, and the other 30
      participants had an additional factor of white noise during both testing
      sessions. Measures of memory and psychomotor performance are reported. RESULTS:
      The stressor (white noise) resulted in poorer memory performance only when
      participants had consumed alcohol the night before testing (F = 7.45, 1/66 df, p
      < .01). Stress also had a detrimental effect on simple reaction time the morning
      after alcohol consumption in both the task with regular interstimulus interval (F
      = 4.61, 1/65 df, p < .05) and irregular interstimulus interval (F = 4.45, 1/65
      df, p < .05). The five-choice reaction time task revealed that initial move time
      and return time were slowed by stress and following a night of intoxication, but
      these factors did not interact. Stress interacted with time of testing and state
      in the measure of decision time, indicating that noise has a detrimental effect
      during the hangover state early in the morning and a detrimental effect during
      the no-hangover state early in the afternoon. CONCLUSIONS: The addition of a
      stressor results in a significant deterioration in memory and psychomotor
      performance when persons are in the compromised hangover condition.

PMID- 17446986
TI  - Five-factor model personality traits associated with alcohol-related diagnoses in
      a clinical sample.
AB  - OBJECTIVE: Personality variables may have important implications for the
      description and treatment of individuals with alcohol problems. The purpose of
      this article was to examine the specificity of previously observed trait/alcohol
      relations and the temporal relations of trait elevations and alcohol problems.
      METHOD: The relationships between Five-Factor Model personality traits, as
      measured by the Revised NEO Personality Inventory, and past and current alcohol
      diagnoses were examined among 704 participants in the Collaborative Longitudinal
      Personality Disorders Study (CLPS). RESULTS: Results suggest that the traits
      previously found to be associated with alcohol-related problems in nonclinical
      populations also differentiate patients with alcohol-use disorders from other
      patients in the CLPS sample and that these traits correspond to findings using
      other personality models. In particular, alcohol use is characterized by
      relatively high impulsiveness and excitement seeking and low agreeableness
      (particularly trust) and conscientiousness (particularly deliberation and
      dutifulness). Although these traits were more specific to alcohol misuse than to
      general impairment in functioning, they were equally related to alcohol and
      substance-use diagnoses. There were few if any traits that differentiated
      individuals with current use diagnoses from those with a history of alcohol
      problems. CONCLUSIONS: Identified traits appear to represent stable
      predispositions to, or enduring effects of, substance use that are more specific
      than those that indicate general psychiatric impairment.

PMID- 17446987
TI  - The alcohol use disorders identification test for detecting at-risk drinking: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: The purpose of this study was to perform a systematic review of the
      diagnostic accuracy of the Alcohol Use Disorders Identification Test (AUDIT) for
      detecting at-risk drinking. METHOD: The MEDLINE, PsycINFO, Science Citation Index
      Expanded, BIOSIS Previews, Cumulative Index to Nursing and Allied Health
      Literature (CINAHL), MEDION, and Cochrane Library databases were searched for
      relevant studies. The criteria for inclusion were a valid reference standard,
      AUDIT consisting of 10 items, avoiding bias that may result from how the
      reference standard was obtained, and when and how many participants were tested.
      Data were extracted independently by two reviewers. Data synthesis was performed
      by applying direct pooling of proportions and random effects model for likelihood
      ratios and diagnostic odds ratio. RESULTS: Twenty-three studies were included in
      the systematic review, 19 of which were included in the meta-analysis. With a
      cutoff of 8 points, sensitivity ranged from .31 to .89 and specificity ranged
      from .83 to .96 across the eight studies conducted in primary care. A single
      trial in general hospital inpatients found a sensitivity of .93 and a specificity
      of .94; another trial in emergency-department patients found a sensitivity of .72
      and a specificity of .88. A study in university students found a sensitivity of
      .82 and a specificity of .78. Three studies in elderly patients found
      sensitivities between .55 and .83 at a pooled specificity of .96. There was large
      heterogeneity between study results, which could only partly be explained by
      setting diversity. The analysis of results with population-specific cutoff points
      led to similar findings. CONCLUSIONS: Findings on the diagnostic performance of
      the AUDIT proved to be largely heterogeneous. Its use should be restricted to
      primary care populations, inpatients, and elderly patients.

PMID- 17446988
TI  - The factor structure of the Alcohol Use Disorders Identification Test (AUDIT).
AB  - OBJECTIVE: Past research assessing the factor structure of the Alcohol Use
      Disorders Identification Test (AUDIT) with various exploratory and confirmatory
      factor analytic techniques has identified one-, two-, and three-factor solutions.
      Because different factor analytic procedures may result in dissimilar findings,
      we examined the factor structure of the AUDIT using the same factor analytic
      technique on two new large clinical samples and on archival data from six samples
      studied in previous reports. METHOD: Responses to the AUDIT were obtained from
      participants who met Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition (DSM-IV), criteria for alcohol dependence in two large randomized
      clinical trials: the COMBINE (Combining Medications and Behavioral Interventions)
      Study (N = 1,337; 69% men) and Project MATCH (Matching Alcoholism Treatments to
      Client Heterogeneity; N = 1,711; 76% men). Supplementary analyses involved six
      correlation matrices of AUDIT data obtained from five previously published
      articles. Confirmatory factor analyses based on one-, two-, and three-factor
      models were conducted on the eight correlation matrices to assess the factor
      structure of the AUDIT. RESULTS: Across samples, analyses supported a correlated,
      two-factor solution representing alcohol consumption and alcohol-related
      consequences. The three-factor solution fit the data equally well, but two
      factors (alcohol dependence and harmful alcohol use) were highly correlated. The
      one-factor solution did not provide a good fit to the data. CONCLUSIONS: These
      findings support a two-factor solution for the AUDIT (alcohol consumption and
      alcohol-related consequences). The results contradict the original three-factor
      design of the AUDIT and the prevalent use of the AUDIT as a one-factor screening
      instrument with a single cutoff score.

PMID- 17446989
TI  - T/natural killer-cell lymphoma of the testis with cutaneous and subcutaneous soft
      tissue involvement: a management problem.

PMID- 17446990
TI  - Effects of octenidine HCl on liver tissue: could it be an alternative scolicidal
      for Hidatid disease?
AB  - Octenidine HCl is new topical antiseptic solution for wounds and abdominal
      washing that has been found to be highly effective for inactivating scolices in
      an in vitro study. However, the effects of octenidine HCl on the liver are not
      yet known. The aim of this study was to determine if there are any
      histopathologic changes after injecting octenidine HCl into the liver. A group of
      50 male Sprague-Dawley rats were included in the study and randomly divided into
      five groups of 10 rats each, as follows: sham group; 0.09% NaCl group; 20% NaCl
      group; undiluted octenidine HCl group; 1% octenidine HCl group. The scolicidal
      agents (0.3 ml) were directly injected into the left lobe of the liver (except in
      the sham group). At 3 and 7 days after the injection, the rats were sacrificed,
      and the left lobe of the liver was harvested. Liver tissue was scored for degree
      of necrosis and the diameter of the necrosis examined under light microscopy. The
      highest scores were found in the undiluted octenidine HCl group, although a
      similar effect was observed in the 20% NaCl group. There was no necrosis in the
      sham group, the 0.09% NaCl group, or the 1% octenidine HCl group. All of the
      injury was coagulation-type necrosis. No mortality was observed throughout the
      study. The 1% octenidine HCl solution could thus be used as a scolicidal agent in
      liver tissue, whereas the undiluted form of octenidine and 20% NaCl solutions
      were shown to cause necrosis when directly injected into liver tissue in our
      animal model.

PMID- 17446991
TI  - Filling a void: thyroid cancer surgery information on the internet.
AB  - BACKGROUND: Thyroid cancer incidence is increasing, making it an important public
      health issue. Many patients use the Internet for health-related decisions. Our
      purposes were to measure the quality of thyroid cancer surgery information on the
      Internet, and to identify quality predictors. METHODS: The 50 most popular
      thyroid cancer websites from Google, Yahoo, and MSN were identified. A novel 55
      point instrument based on current clinical practice guidelines was designed and
      used by a Delphi panel of 5 "blinded" endocrine surgeons to assess website
      information. Each website was independently evaluated by two surgeons. Quality
      was related to website demographic data using the Student's t-test, chi-square,
      and ANOVA analyses. RESULTS: Inter-rater reliability for quality scores was
      excellent (kappa = 0.81). Mean (% of overall quality) score was 21 (38%), and
      mean score for surgical content was low at 3.5 (29%). Only 50% of sites discussed
      indications for surgery; 8% length of surgery/anesthesia; 42% the role of
      lymphadenectomy; 44% recurrent laryngeal nerve injury/hoarseness and 42%
      hypoparathyroidism as potential complications; 16% recovery; and 20%
      recommendations for choosing a thyroid surgeon. Only 38% were updated within 2
      years. On univariate analysis, no significant associations were found between
      surgical quality score and website country of origin, currency, sponsorship,
      authorship, oversight, or references. CONCLUSIONS: Thyroid cancer surgery
      websites on the Internet are incomplete and outdated. No predictors of quality
      were identified. Significant improvement is needed in regulating information
      about thyroid cancer surgery on the Internet, and surgeons may contribute to this
      effort.

PMID- 17446992
TI  - The role of echo-laparoscopy in abdominal surgery: five years' experience in a
      dedicated center.
AB  - BACKGROUND: For more than 20 years intraoperative ultrasonography (IOUS) has been
      considered an important diagnostic tool in abdominal surgery. In the last few
      years, with the spread of laparoscopic surgery, echo-laparoscopy (LIOUS) has
      gradually replaced open ultrasonography, aiming to achieve similar results.
      METHODS: LIOUS was performed using an ALOKA 5.500 device, provided with a linear
      flexible laparoscopic probe that was compatible with a 10-mm port. IOUS was
      performed by means of a linear side-view, T-shaped or microconvex probe. The
      probes were sterilized with hydrogen peroxide. No water bath was used during the
      surgical examination, but full contact of the probe with the surface of the
      involved organ was always attempted. From 2001 to 2005, 36 liver resections, 40
      pancreas procedures, 203 procedures for suspected common bile duct calculi, 541
      colon and 82 stomach resections, and 82 adrenal surgery procedures were
      performed. IOUS or LIOUS was performed in 432 patients (43.8%). All livers and
      pancreases underwent intraoperative ultrasound, while biliary, colonic, gastric,
      and adrenal pathologies were selectively studied when there were doubts about the
      location and extension of the disease. RESULTS: IOUS and LIOUS were valuable
      diagnostic procedures, supplying relevant clinical information in 65.1% of the
      patients and modifying the surgical approach in 17.2%. LIOUS was used instead of
      cholangiography to study bile ducts when lythiasis was suspected, achieving high
      diagnostic specificity (98%) and accuracy (100%). Surgical anatomy of the bile
      ducts was correctly identified by LIOUS in every case. DISCUSSION: In our
      experience IOUS and LIOUS were of the utmost importance in better defining
      staging of disease, infiltration of neighboring structures, number and size of
      nodular lesions, and anatomy of the hepatic pedicle and intrahepatic structures,
      thus making it possible to more accurately plan surgical procedures.

PMID- 17446993
TI  - Relationships between gray matter metabolic abnormalities and white matter
      inflammation in patients at the very early stage of MS : a MRSI study.
AB  - Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) was used to study
      metabolic abnormalities inside the gray matter (GM) during or distant to white
      matter (WM) inflammatory processes reflected by T(1) gadolinium-enhancing lesions
      in patients at the very early stage of multiple sclerosis (MS). The spectroscopic
      examination was performed in the axial plane using a home-designed acquisition
      weighted, hamming shape, 2D-SE pulse sequence (TE = 135 ms; TR = 1,600 ms).
      Bilateral thalami and the medial occipital cortex were explored in 35 patients
      (15 with and 20 without T(1)-Gd enhancing lesions) with clinically isolated
      syndrome suggestive of MS and in 30 controls. The mean duration since the first
      presenting symptom was 9.1 (+/-6.7) months. The two groups of patients (with or
      without T(1) Gd-enhancing lesions) did not differ in terms of time elapsed since
      the first clinical onset and T(2) lesion load. The spatial contamination of
      surrounding WM tissues was obtained in each GM region by determining the tissue
      component in the ROI from GM and WM probability maps smoothed with the point
      spread function of the MRSI acquisition. Contribution of WM signal was important
      (60%) inside thalami while the region centered on the medial occipital cortex was
      well representative of GM metabolism (>70%). Comparisons of relative metabolite
      levels (ratios of each metabolite over the sum of all metabolites) between all
      patients and controls showed significant decrease in relative N-acetyl aspartate
      (NAA) levels, increase in relative choline-containing compounds (Cho) levels and
      no change in relative creatine/phosphocreatine levels inside the three ROIs.
      Decrease in relative NAA levels and increase in relative Cho levels were found in
      patients with inflammatory activity, while no metabolic alterations were present
      in patients without T(1) Gd-enhancing lesions. These results suggest that
      abnormalities in GM metabolism observed in patients at the very early stage of MS
      are mainly related to neuronal dysfunction occurring during acute inflammatory
      processes.

PMID- 17446994
TI  - Treatment of active secondary progressive multiple sclerosis with treosulfan.
AB  - OBJECTIVE: To study the safety and efficacy of treosulfan, a cytotoxic alkylating
      agent, in patients with active secondary progressive multiple sclerosis.
      BACKGROUND: Treosulfan (L-threitol-1,4-bis(methanesulfonate)) is a bifunctional
      alkylating agent with a favorable profile of side effects, approved for the
      treatment of ovarian cancer. Treosulfan has previously been shown to reduce the
      severity of experimental allergic encephalomyelitis under pre-therapeutic and
      therapeutic conditions. In human peripheral blood mononuclear cells, treosulfan
      reduces proliferative capacity and increases apoptosis. STUDY DESIGN: This is a
      nonrandomized, open label study conducted in two centers. Eleven patients with
      active secondary progressive MS that failed to or did not qualify for approved
      disease modifying drugs were treated with treosulfan for 1 year. Patients
      received intravenous infusions of 7 g/m(2) every 4 weeks for 3 months (cycles 1
      4, induction phase) with a predefined one-step dose escalation, thereafter every
      3 months for the following 9 months (cyles 5-7, maintainance phase). Cranial MRI
      was performed every 3 months, EDSS and MSFC as well as physical examination were
      assessed at each clinical visit. RESULTS: Treatment with treosulfan was safe and
      well tolerated. Nine of 11 patients remained on study drug over the complete
      treatment period and showed clinical stabilisation or improvement as determined
      by EDSS and MSFC. Two patients discontinued study drug because of leukocytopenia
      and withdrawal of consent, respectively. No clinical relapses were observed
      during the treatment period. Thus, the median number of relapses per year was
      reduced signifi- cantly by 1.5 (range -3 to 0), p < 0.016, compared to prestudy.
      Therapy with treosulfan lead to a clear reduction of MRI activity as revealed by
      a reduced number of Gd + enhancing lesions on T1 weighted images. The mean number
      and volume of T2 lesions remained unchanged over 1 year. Four out of 9 patients
      under treosulfan showed no detectable disease activity (no Gd enhancing lesions,
      no new or newly enlarging T2 lesions). CONCLUSIONS: Application of treosulfan in
      MS was safe and well tolerated. Further studies are warranted to evaluate the
      efficacy of this treatment in secondary progressive MS.

PMID- 17446995
TI  - Spinal subarachnoid hemorrhage due to ruptured solitary aneurysm at thoracolumbar
      level with fatal outcome.

PMID- 17446996
TI  - The neuralgic amyotrophy consultation.
AB  - Neuralgic amyotrophy is a distinct clinical syndrome with acute severe pain and
      patchy paresis in the shoulder and arm region. The clinical phenotype was
      recently found to be more comprehensive and the long-term prognosis less
      optimistic than usually assumed for many patients. The disorder can be idiopathic
      or hereditary in an autosomal dominant fashion, with only few phenotypical
      variations between the two. This article provides a practical overview of current
      knowledge on the clinical presentation, diagnosis, pathogenesis and the treatment
      of pain and complications.

PMID- 17446997
TI  - Brain atrophy and white matter hyperintensity change in older adults and
      relationship to blood pressure. Brain atrophy, WMH change and blood pressure.
AB  - Hypertension is a major risk factor for stroke and dementia and is associated
      with white matter hyperintensities (WMH) and reduced brain volumes. We measured
      the increase in WMH volume, and rate of cerebral atrophy over two years, in
      hypertensive subjects participating in the Study on COgnition and Prognosis in
      the Elderly (SCOPE), receiving candesartan or placebo, and normotensive controls.
      We recruited 163 subjects who had MRI (FLAIR and volumetric T1) at 2 and 4 years
      after baseline assessment. From these two scans, volumetric change in WMH (n =
      133) and brain atrophy rates (n = 95) were determined. Total WMH fraction
      increased in both normotensive and treated hypertensive groups (p < 0.01) median
      change: 0.05% of brain volume [range: -0.45% to 1.51%]. Deep WMH increased in
      hypertensive (p = 0.001) but not the normotensive group. The number of subjects
      with an increase of total WMH in the 5(th) quintile differed between the
      treatment groups (chi square p = 0.006), being greatest in the placebo group
      (32%), then candesartan (20%) then normotensive (5%). Regression analysis found
      significant predictors of change in WMH to be blood pressure and initial deep
      WMH, but not treatment group. Increased atrophy rate was predicted by baseline
      systolic blood pressure (p = 0.02) but was not associated with measures of WMH.
      Similar to WMH, there was a trend with treatment, with atrophy in normotensive <
      Candesartan < Placebo (Spearman's rho = 0.23, p = 0.026). Hypertension in older
      people is associated with increased rates of progressive whole brain atrophy and
      an increase in WMH. These changes are independent. Successful hypertension
      treatment was associated with reduced risk of WMH progression and possibly brain
      atrophy.

PMID- 17446998
TI  - L-dopa dose and the duration and severity of dyskinesia in primed MPTP-treated
      primates.
AB  - Most patients with Parkinson's disease (PD) develop dyskinesia and other motor
      complications after prolonged L-dopa use. We now report on the relationship
      between L-dopa dose and the duration and severity of dyskinesia in L-dopa-primed
      MPTP-treated primates with marked nigral degeneration mimicking late stage PD.
      With increasing doses of L-dopa, locomotor activity increased and motor
      disability declined. The duration of dyskinesia following L-dopa administration
      increased dose-dependently, and showed a linear correlation with total locomotor
      activity. In addition, the time-course of dyskinesia paralleled closely that of
      locomotor activity in a dose-dependent manner. In contrast, severity of
      dyskinesia showed a non-linear correlation with total locomotor activity, low
      doses of L-dopa eliciting severe dyskinesia for short periods of time. The
      threshold for dyskinesia induction and the antiparkinsonian effects of L-dopa
      appear very similar in primed MPTP primates mimicking late stage PD. Reducing
      individual doses of L-dopa to avoid severe dyskinesia can markedly compromise the
      antiparkinsonian response. Our results extend the relevance of the dyskinetic
      MPTP-treated primate in studying the genesis of involuntary movements occurring
      in L-dopa treated patients with PD.

PMID- 17446999
TI  - Cross-sectional study discloses a positive family history for Parkinson's disease
      and male gender as epidemiological risk factors for substantia nigra
      hyperechogenicity.
AB  - Hyperechogenicity of the substantia nigra (SN) has been proposed to be a typical
      finding in Parkinson's disease (PD) and a marker of vulnerability to
      nigrostriatal dysfunction in healthy subjects. This large cross-sectional study
      including 1120 subjects older than 50 years without any signs of PD was performed
      to evaluate the association of SN hyperechogenicity and other proposed
      epidemiological risk factors for PD. Among all variables assessed only family
      history of PD and male gender proved to be significantly associated with SN
      hyperechogenicity, indicating a genetic predisposition for the ultrasound marker.

PMID- 17447000
TI  - Modulation of antidepressant-like activity of magnesium by serotonergic system.
AB  - The influence of magnesium on the action of antidepressants drugs with different
      pharmacological profiles citalopram, reboxetine and tianeptine, was investigated
      in the forced swim test (FST) in mice. Magnesium (10 mg Mg/kg) given with
      reboxetine (2.5 mg/kg) did not change the behavior of animals in the FST. A
      synergistic effect was seen when magnesium (10 mg Mg/kg) was given jointly with
      citalopram (15 mg/kg) or tianeptine (20 mg/kg) in the FST, without accompanying
      changes in locomotor activity. Moreover, the antidepressant-like effect of
      magnesium (30 mg Mg/kg) was significantly reduced by pretreatment of mice with an
      inhibitor of serotonin synthesis, p-chlorophenylalanine (pCPA, 200 mg/kg). Thus,
      the antidepressant-like action of magnesium in the FST seems to involve an
      interaction with serotonergic system.

PMID- 17447001
TI  - The effect of l-deprenyl on tissue mRNA expressions of NOS isoforms and NO levels
      in an experimental diabetes mellitus model.
AB  - Diabetes and aging share some common mechanisms in their pathogenesis and
      diabetics are more prone to diseases of the elderly. Seeking for therapies likely
      to be proposed in the synchronised treatment of aging and diabetes is of great
      interest and l-deprenyl, a selective monoamine oxidase (MAO-B) inhibitor, is a
      possible candidate with its antioxidant, antiapoptotic and neuroprotective
      properties. Tissue MAO, NO and mRNA expression of nitric oxide (NO) synthase
      (NOS) isoforms were assessed in streptozotocin (STZ)-induced diabetic rats to
      evaluate the effect of l-deprenyl treatment. Twelve weeks of treatment had no
      significant effect on NO levels. Four-weeks treatment decreased tissue MAO
      activities and caused a decrease in expression of NOS-2 and NOS-3 in heart tissue
      of both controls and diabetics, and a decrease of liver NOS-3 expression in
      controls (p < 0.05). l-Deprenyl, causing a decrease in tissue NOS expressions,
      might be of benefit by protecting the organism from the toxic radical effects of
      NO.

PMID- 17447003
TI  - Mitochondrial DNA geneflow indicates preferred usage of the Levant Corridor over
      the Horn of Africa passageway.
AB  - Both the Levantine Corridor and the Horn of Africa route have figured prominently
      in early hominid migrations from Africa to Eurasia. To gauge the importance of
      these two African-Asian thoroughfares in the demic movements of modern man, we
      surveyed the mtDNA control region variation and coding polymorphisms of 739
      individuals representing ten African and Middle Eastern populations. Two of these
      collections, Egypt and Yemen, are geographically close to the Levant and Horn of
      Africa, respectively. In this analysis, we uncover genetic evidence for the
      preferential use of the Levantine Corridor in the Upper Paleolithic to Neolithic
      dispersals of haplogroups H, J*, N1b, and T1, in contrast to an overwhelming
      preference in favor of the Horn of Africa for the intercontinental expansion of
      M1 during the Middle to Upper Paleolithic. Furthermore, we also observed a higher
      frequency of sub-Saharan mtDNA compared to NRY lineages in the Middle Eastern
      collections, a pattern also seen in previous studies. In short, the results of
      this study suggest that several migratory episodes of maternal lineages occurred
      across the African-Asian corridors since the first African exodus of modern Homo
      sapiens sapiens.

PMID- 17447002
TI  - Platelet phospholipase A2 activity in patients with Alzheimer's disease, vascular
      dementia and ischemic stroke.
AB  - Phospholipase A(2) (E.C. 3.1.1.4, PLA(2)) plays an essential role in metabolism
      of membrane phospholipids, it is related to inflammatory reactions, secretion of
      amyloid precursor protein and activation of NMDA receptor after ischemia. In the
      present study we investigated PLA(2) activity in platelets from 37 Alzheimer's
      disease (AD) patients, 32 vascular dementia (VaD) patients and 32 individuals
      with ischemic stroke as compared to 27 healthy elderly controls. PLA(2) activity
      was determined using radiometric assay. Mean platelet PLA(2) activity was
      increased in individuals with Alzheimer's disease (p < 0.001). In VaD group the
      enzyme activity was between the values in AD and controls, these differences
      being significant from both groups. In the group of patients with ischemic stroke
      mean PLA(2) activity was higher either 48 h after the stroke or 7 days later (in
      both cases p < 0.001). The results may be particularly interesting in light of
      the fact, that inhibitors of PLA(2) activity are known.

PMID- 17447004
TI  - Effect of olfactory ensheathing cells on reactive astrocytes in vitro.
AB  - Olfactory ensheathing cells have been used in several studies to promote repair
      in the injured spinal cord. However, cellular interaction between olfactory
      ensheathing cells and glial cells induced to be reactive in the aftermath of
      injury site has not been investigated. Using an in vitro model of astrogliosis,
      we show that reactive astrocytes expressed significantly less glial fibrillary
      acidic protein (GFAP) when cultured both in direct contact with olfactory
      ensheathing cells and when the two cell types were separated by a porous
      membrane. Immunofluorescence staining also suggested that reactive astrocytes
      showed decreased chondroitin sulfate proteoglycans in the presence of olfactory
      ensheathing cells, although the reduction was not statistically significant. No
      down-regulation of GFAP was observed when reactive astrocytes were similarly
      cultured with Schwann cells. Cell viability assay and bromodeoxyuridine uptake
      showed that proliferation of reactive astrocytes was significantly increased in
      the presence of olfactory ensheathing cells and Schwann cells.

PMID- 17447005
TI  - Dual antiglioma action of metformin: cell cycle arrest and mitochondria-dependent
      apoptosis.
AB  - The present study reports for the first time a dual antiglioma effect of the well
      known antidiabetic drug metformin. In low-density cultures of the C6 rat glioma
      cell line, metformin blocked the cell cycle progression in G(0)/G(1) phase
      without inducing significant cell death. In confluent C6 cultures, on the other
      hand, metformin caused massive induction of caspase-dependent apoptosis
      associated with c-Jun N-terminal kinase (JNK) activation, mitochondrial
      depolarization and oxidative stress. Metformin-triggered apoptosis was completely
      prevented by agents that block mitochondrial permeability transition (cyclosporin
      A) and oxygen radical production (N-acetylcisteine), while the inhibitors of JNK
      activation (SP600125) or glycolysis (sodium fluoride, iodoacetate) provided
      partial protection. The antiglioma effect of metformin was reduced by compound C,
      an inhibitor of AMP-activated protein kinase (AMPK), and was mimicked by the AMPK
      agonist AICAR. Similar effects were observed in the human glioma cell line U251,
      while rat primary astrocytes were completely resistant to the antiproliferative
      and proapoptotic action of metformin.

PMID- 17447006
TI  - Aminoglycoside antibiotics: old drugs and new therapeutic approaches.
AB  - Aminoglycoside antibiotics kill bacteria by binding to the ribosomal decoding
      site and reducing fidelity of protein synthesis. Since the discovery of these
      natural products over 50 years ago, aminoglycosides have provided a mainstay of
      antibacterial therapy of serious Gram-negative infections. In recent years,
      aminoglycosides have become important tools to study molecular recognition of
      ribonucleic acid (RNA). In an ingenious exploitation of the aminoglycosides'
      mechanism of action, it has been speculated that drug-induced readthrough of
      premature stop codons in mutated messenger RNAs might be used to treat patients
      suffering from certain heritable genetic disorders.

PMID- 17447007
TI  - New insights into the molecular mechanisms of sperm-egg interaction.
AB  - At the moment of insemination millions of mammalian sperm cells are released into
      the female reproductive tract in order to find a single cell - the oocyte. The
      spermatozoa subsequently ignore the thousands of cells they make contact with
      during their journey to the site of fertilisation, until they reach the surface
      of the oocyte. At this point, they bind tenaciously to the acellular coat, known
      as the zona pellucida, that surrounds the oocyte and initiate the chain of
      cellular interactions that will culminate in fertilization. These exquisitely
      cell- and species-specific recognition events are among the most strategically
      important cellular interactions in biology. Understanding the cellular and
      molecular mechanisms that underpin them has implications for diagnosis of the
      aetiology of human infertility and the development of novel targets for fertility
      regulation. Herein, we describe two models indicating the plethora of highly
      orchestrated molecular interactions underlying successful sperm zona binding and
      sperm oocyte fusion.

PMID- 17447008
TI  - Molecular targets of non-steroidal anti-inflammatory drugs in neurodegenerative
      diseases.
AB  - During the last decade, interest has grown in the beneficial effects of non
      steroidal anti-inflammatory drugs (NSAIDs) in neurodegeneration, particularly in
      pathologies such as Alzheimer's (AD) and Parkinson's (PD) disease. Evidence from
      epidemiological studies has indicated a decreased risk for AD and PD in patients
      with a history of chronic NSAID use. However, clinical trials with NSAIDs in AD
      patients have yielded conflicting results, suggesting that these drugs may be
      beneficial only when used as preventive therapy or in early stages of the
      disease. NSAIDs may also have salutary effects in other neurodegenerative
      diseases with an inflammatory component, such as multiple sclerosis and
      amyotrophic lateral sclerosis. In this review we analyze the molecular
      (cyclooxygenases, secretases, NF-kappaB, PPAR, or Rho-GTPasas) and cellular
      (neurons, microglia, astrocytes or endothelial cells) targets of NSAIDs that may
      mediate the therapeutic function of these drugs in neurodegeneration.

PMID- 17447009
TI  - Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor
      meloxicam on human glioma cells.
AB  - The COX-2 protein is frequently overexpressed in human malignant gliomas. This
      expression has been associated with their aggressive growth characteristics and
      poor prognosis for patients. Targeting the COX-2 pathway might improve glioma
      therapy. In this study, the effects of the selective COX-2 inhibitor meloxicam
      alone and in combination with irradiation were investigated on human glioma cells
      in vitro. A panel of three glioma cell lines (D384, U87 and U251) was used in the
      experiments from which U87 cells expressed constitutive COX-2. The response to
      meloxicam and irradiation (dose-range of 0-6 Gy) was determined by the clonogenic
      assay, cell proliferation was evaluated by growth analysis and cell cycle
      distribution by FACS. 24-72 h exposure to 250-750 microM meloxicam resulted in a
      time and dose dependent growth inhibition with an almost complete inhibition
      after 24 h for all cell lines. Exposure to 750 microM meloxicam for 24 h
      increased the fraction of cells in the radiosensitive G(2)/M cell cycle phase in
      D384 (18-27%) and U251 (17-41%) cells. 750 microM meloxicam resulted in
      radiosensitization of D384 (DMF:2.19) and U87 (DMF:1.25) cells, but not U251
      cells (DMF:1.08). The selective COX-2 inhibitor meloxicam exerted COX-2
      independent growth inhibition and radiosensitization of human glioma cells.

PMID- 17447010
TI  - Unexpected dementia following prophylactic cranial irradiation for small cell
      lung cancer: case report.
AB  - OBJECT: Prophylactic cranial irradiation (PCI) is commonly offered to patients
      with limited stage primary small cell lung cancer following a complete response.
      METHODS: We present the unique case of a 76-year-old woman treated with PCI with
      a dose of 30 Gy in 15 fractions, at 200 cGy per fraction who developed
      progressive dementia. CONCLUSIONS: This is the first reported case of dementia
      from PCI at this low dose per fraction. Patients need to be counseled regarding
      the risks and benefits of treatment, including dementia with treatment and risk
      of sequelae from CNS metastasis without treatment. The authors review the data
      supporting PCI and the incidence of radiation associated dementia.

PMID- 17447011
TI  - Protein-protein interaction site mapping using NMR-detected mutational scanning.
AB  - We demonstrate a novel NMR method for the mapping of protein-protein interaction
      sites. In our approach protein-protein binding sites are mapped by competition
      binding experiments using indirect NMR reporter technology and Ala positional
      scanning. The methodology provides high sensitivity, ease of implementation and
      high-throughput capabilities. The feasibility of the technique is demonstrated
      with an application to the beta-Catenin/Tcf4 complex.

PMID- 17447012
TI  - Wolbachia-induced cytoplasmic incompatibility in Japanese populations of
      Tetranychus urticae (Acari: Tetranychidae).
AB  - Intracellular bacteria of the genus Wolbachia (alpha Proteobacteria) induce
      cytoplasmic incompatibility (CI) in many arthropod species, including spider
      mites, but not all Wolbachia cause CI. In spider mites CI becomes apparent by a
      reduced egg hatchability and a lower daughter:son ratio: CI in haplodiploid
      organisms in general was expected to produce all-male offspring or a male-biased
      sex ratio without any death of eggs. In a previous study of Japanese populations
      of Tetranychus urticae, two out of three green-form populations tested were
      infected with non-CI Wolbachia strains, whereas none of six red-form populations
      harbored Wolbachia. As the survey of Wolbachia infection in T. urticae is still
      fragmentary in Japan, we checked Wolbachia infection in thirty green-form
      populations and 29 red-form populations collected from a wide range of Japanese
      islands. For Wolbachia-infected populations, we tested the effects of Wolbachia
      on the reproductive traits and determined the phylogenetic relationships of the
      different strains of Wolbachia. All but one green-form populations were infected
      with Wolbachia and all strains belonged to the subgroup Ori when the wsp gene was
      used to determine the phylogenetic relationships of different strains of
      Wolbachia. Six out of 29 red-form populations harbored Wolbachia and the infected
      strains belonged to the subgroups Ori and Bugs. Twenty-four of 29 infected green
      form populations and five of six infected red-form populations induced CI among
      the hosts. Thus, CI-Wolbachia strains are widespread in Japan, and no
      geographical trend was observed in the CI-Wolbachia. Although three red-form
      populations harbored other intracellular bacteria Cardinium, they did not affect
      host reproduction.

PMID- 17447013
TI  - Evaluation of low humidity treatments to control Acarus farris (Acari: Acaridae)
      in Cabrales cheese.
AB  - Laboratory experiments were conducted to establish the best combination of
      relative humidity (r.h.) and time of exposure to be applied on Cabrales cheeses
      infested with Acarus farris. Laboratory assays revealed that less than 30 h were
      required to obtain 90% mortality of mites at 50% and 60% r.h. Males were more
      susceptible than females to low relative humidity, since their lethal period
      values (LP) were lower than those obtained for females at the same relative
      humidity. Moreover, the response within sexes to low moisture treatments changed
      as exposure time increased, since the LP50 obtained for each sex at 50 and 60%
      r.h. were statistically different whereas the LP90 showed no significant
      differences within sexes. Accordingly, two modifications of the traditional
      maturing process were established to assess the efficacy of low moisture
      treatments to control A. farris on infested cheeses. The first modification
      consisted of one single exposure of 48 h at 50% r.h. and the second one consisted
      of two exposures of 48 h at 50% r.h. separated by a time interval of 15 days. No
      significant differences in final population density were observed for both low
      moisture treatments compared to control cheeses. Therefore, low humidity
      treatments are not effective to control A. farris in Cabrales cheese, despite the
      good results obtained in laboratory assays.

PMID- 17447014
TI  - Effects of temperature, storage period and the number of individuals on the
      detection of the false spider mite Cardinium endosymbiont.
AB  - Cardinium have been found as endosymbionts of Brevipalpus phoenicis, the mite
      vector of the Citrus leprosis virus. With the long-term objective being to
      understand the mechanisms of plant-virus-vector interactions, we evaluated the
      different storage conditions and periods, as well as the number of mites needed
      for PCR-amplification of such endosymbionts, making it possible to collect mites
      in different geographical regions without prolonged storage compromising
      subsequent analyses.

PMID- 17447015
TI  - Thapsigargin, a selective inhibitor of sarco-endoplasmic reticulum Ca2+ -ATPases,
      modulates nitric oxide production and cell death of primary rat hepatocytes in
      culture.
AB  - Increased cytosolic calcium ([Ca2+]i) and nitric oxide (NO) are suggested to be
      associated with apoptosis that is a main feature of many liver diseases and is
      characterized by biochemical and morphological features. We sought to investigate
      the events of increase in [Ca2+]i and endoplasmic reticulum (ER) calcium
      depletion by thapsigargin (TG), a selective inhibitor of sarco-ER-Ca2+ -ATPases,
      in relation to NO production and apoptotic and necrotic markers of cell death in
      primary rat hepatocyte culture. Cultured hepatocytes were treated with TG (1 and
      5 micromol/L) for 0-24 or 24-48 h. NO production and inducible NO synthase (iNOS)
      expression were determined as nitrite levels and by iNOS-specific antibody,
      respectively. Hepatocyte apoptosis was estimated by caspase-3 activity, cytosolic
      cytochrome c content and DNA fragmentation, and morphologically using Annexin
      V/propidium iodide staining. Hepatocyte viability and mitochondrial activity were
      evaluated by ALT leakage and MTT test. Increasing basal [Ca2+]i by TG, NO
      production and apoptotic/necrotic parameters were altered in different ways,
      depending on TG concentration and incubation time. During 0-24 h, TG dose
      dependently decreased iNOS-mediated spontaneous NO production and simultaneously
      enhanced hepatocyte apoptosis. In addition, TG 5 micromol/L produced secondary
      necrosis. During 24-48 h, TG dose-dependently enhanced basal NO production and
      rate of necrosis. TG 5 micromol/L further promoted mitochondrial damage as
      demonstrated by cytochrome c release. A selective iNOS inhibitor, aminoguanidine,
      suppressed TG-stimulated NO production and ALT leakage from hepatocytes after 24
      48 h. Our data suggest that the extent of the [Ca2+]i increase and the modulation
      of NO production due to TG treatment contribute to hepatocyte apoptotic and/or
      necrotic events.

PMID- 17447016
TI  - Oxidative stress activates insulin-like growth factor I receptor protein
      expression, mediating cardiac hypertrophy induced by thyroxine.
AB  - Thyroxine can cause cardiac hypertrophy by activating growth factors, such as IGF
      I (insulin-like growth factor-I). Since oxidative stress is enhanced in the
      hyperthyroidism, it would control protein expression involved in this
      hypertrophy. Male Wistar rats were divided into four groups: (I) control, (II)
      vitamin E-supplemented (20 mg/kg/day subcutaneous), (III) hyperthyroid (thyroxine
      12 mg/l, in drinking water), and (IV) hyperthyroid + vitamin E. After 4 weeks,
      the contractility and relaxation indexes of left ventricle (LV), and cardiac mass
      were increased by 54%, 60%, and 60%, respectively, in hyperthyroid group. An
      increase in lipid peroxidation (around 40%), and a decrease in total glutathione
      (by 20%) was induced by thyroxine and avoided by vitamin E administration.
      Superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were
      increased (by 83% and 54%, respectively) in hyperthyroid, and vitamin E avoided
      changes in SOD. Protein expression of SOD, GST, and IGF-I receptor (IGF-IR) were
      increased (by 87%, 84%, and 60%, respectively) by thyroxine, and vitamin E
      promoted a significant reduction in SOD and IGF-IR expression (by 36% and 17%,
      respectively). These results indicate that oxidative stress is involved in
      cardiac hypertrophy, and suggest a role for IGF-IR as a mediator of this adaptive
      response in experimental hyperthyroidism.

PMID- 17447017
TI  - Beneficial effects of ketogenic diet in obese diabetic subjects.
AB  - OBJECTIVE: Obesity is closely linked to the incidence of type II diabetes. It is
      found that effective management of body weight and changes to nutritional habits
      especially with regard to the carbohydrate content and glycemic index of the diet
      have beneficial effects in obese subjects with glucose intolerance. Previously we
      have shown that ketogenic diet is quite effective in reducing body weight.
      Furthermore, it favorably alters the cardiac risk factors even in hyperlipidemic
      obese subjects. In this study the effect of ketogenic diet in obese subjects with
      high blood glucose level is compared to those with normal blood glucose level for
      a period of 56 weeks. MATERIALS AND METHODS: A total of 64 healthy obese subjects
      with body mass index (BMI) greater than 30, having high blood glucose level and
      those subjects with normal blood glucose level were selected in this study. The
      body weight, body mass index, blood glucose level, total cholesterol, LDL
      cholesterol, HDL-cholesterol, triglycerides, urea and creatinine were determined
      before and at 8, 16, 24, 48, and 56 weeks after the administration of the
      ketogenic diet. RESULTS: The body weight, body mass index, the level of blood
      glucose, total cholesterol, LDL-cholesterol, triglycerides, and urea showed a
      significant decrease from week 1 to week 56 (P < 0.0001), whereas the level of
      HDL-cholesterol increased significantly (P < 0.0001). Interestingly these changes
      were more significant in subjects with high blood glucose level as compared to
      those with normal blood glucose level. The changes in the level of creatinine
      were not statistically significant. CONCLUSION: This study shows the beneficial
      effects of ketogenic diet in obese diabetic subjects following its long-term
      administration. Furthermore, it demonstrates that in addition to its therapeutic
      value, low carbohydrate diet is safe to use for a longer period of time in obese
      diabetic subjects.

PMID- 17447018
TI  - Treatment of small HCC through radiofrequency ablation and laser ablation.
      Comparison of techniques and long-term results.
AB  - PURPOSE: The aim of this trial was to compare the results obtained using laser
      ablation (LA) and radiofrequency ablation (RFA) to treat small hepatocellular
      carcinomas (HCC). MATERIALS AND METHODS: From 2003 to 2005, a total of 81
      cirrhotic patients (59 Child-Pugh A, 22 Child-Pugh B) presenting a total of 95
      HCC nodules (mean diameter 27.9 mm) were treated with LA (41) and RFA (40).
      RESULTS: Computed tomography (CT) revealed complete tumour ablation in 78% of
      nodules treated with LA and in 94% of those treated with RA; the disease-free
      interval was 16.50+/-8.1 months. The cumulative survival rates were 91.8%, 59%
      and 28.4% at 12, 36 and 60 months, respectively. The patients treated with RFA
      had better survival rates than those treated with LA, although this difference
      was not statistically significant (p=0.3299). Univariate analysis of survival
      revealed statistically significant differences between the Child-Pugh A and B
      groups (p<0.0001), between HCC nodules measuring < or =25 mm and >25 mm
      (p=0.0001) and between patients with a single nodule and with two nodules
      (p=0.0484). CONCLUSIONS: We found LA and RFA to be equally effective. However, RA
      appears more suited to patients with small HCC nodules and in Child-Pugh class A.

PMID- 17447019
TI  - Localization of phosphorylated TrkA in carrier vesicles involved in its nuclear
      translocation in U251 cell line.
AB  - A number of transmembrane receptors are targeted to the nucleus and convincingly
      localized therein. However, what remains a conundrum is how these cell-surface
      receptors end up in the nucleus. In this study, we reported that the
      transmembrane receptor phosphorylated TrkA was located in a series of carrier
      vesicles, including ring-like vesicles near the plasma membrane, large core
      vesicles and small dense core vesicles around the nuclei, as well as in the
      nucleus in human glioma cell line U251 using immunocytochemistry and
      immunofluorescence staining. Meanwhile, we also showed that small dense core
      vesicles budded from large core vesicles, and interacted with the nuclear
      envelope. Accordingly, our results suggested that such a series of membrane
      compartments might be involved in the pathway of nuclear translocation of the
      transmembrane receptor TrkA.

PMID- 17447020
TI  - Glucose transporter 4 can be inserted in the membrane without exposing its
      catalytic site for photolabeling from the medium.
AB  - Insulin stimulates the production of PI(3,4,5)P(3) in muscle cells, and this is
      required to stimulate GLUT4 fusion with the plasma membrane. Introduction of
      exogenous PI(3,4,5)P(3) to muscle cells recapitulates insulin's effects on GLUT4
      fusion with the plasma membrane, but not glucose uptake. This study aims to
      explore the mechanism behind this difference. In L6-GLUT4myc muscle cells, the
      availability of the GLUT4 intracellular C-terminus and extracellular myc epitopes
      for immunoreactivity on plasma membrane lawns was detected with the corresponding
      antibody. The availability of the active site of GLUT4 from extracellular medium
      was assessed by affinity photolabeling with the cell impermeant compound Bio-LC
      ATB-BMPA. 100 nmol/L insulin and 10 mumol/L PI(3,4,5)P(3) caused myc signal gain
      on the plasma membrane lawns by 1.64-fold and 1.58-fold over basal, respectively.
      Insulin, but not PI(3,4,5)P(3), increased photolabeling of GLUT4 and
      immunolabeling with C-terminus antibody by 2.47-fold and 2.04-fold over basal,
      respectively. Upon insulin stimulation, the C-terminus signal gain was greater
      than myc signal gain (2.04-fold vs. 1.64-fold over basal, respectively) in plasma
      membrane lawns. These results indicate that (i) PI(3,4,5)P(3) does not make the
      active site of GLUT4 available from the extracellular surface despite causing
      GLUT4 fusion with the plasma membrane; (ii) the availability of the active site
      of GLUT4 from the extracellular medium and availability of the C-terminus from
      the cytosolic site are correlated; (iii) in addition to stimulating GLUT4
      translocation, insulin stimulation displaces a protein which masks the GLUT4 C
      terminus. We propose that a protein which masks the C-terminus also prevents the
      active site from being available for photolabelling and possibly glucose uptake
      after treatment with PI(3,4,5)P(3).

PMID- 17447021
TI  - Effect of cell cycle inhibitor p19ARF on senescence of human diploid cell.
AB  - To investigate the effect of cell cycle inhibitor p14ARF on replicative
      senescence of human diploid cell, recombinant p19ARF eukaryotic expression vector
      was constructed and p19ARF gene was transfected into human diploid fibroblasts
      (WI-38 cells) by liposome-mediated transfection for overexpression. Then, the
      effects of p19ARF on replicative senescence of WI-38 cells were observed. The
      results revealed that, compared with control cells, the WI-38 cells in which
      p19ARF gene was introduced showed significant up-regulation of p53 and p21
      expression level, decrease of cell generation by 10-12 generations, decline of
      cell growth rate with cell cycle being arrested at G1 phase, increase of positive
      rate of senescent marker SA-beta-gal staining, and decrease of mitochondrial
      membrane potential. The morphology of the transfected fibroblasts presented the
      characteristics changes similar to senescent cells. These results indicated that
      high expression of p19ARF may promote the senescent process of human diploid
      cells.

PMID- 17447022
TI  - Establishment of a novel corneal endothelial cell line from domestic rabbit,
      Oryctolagus curiculus.
AB  - To develop a rabbit corneal endothelial (RCE) cell line, in vitro culture of RCE
      cells was initiated from Oryctolagus curiculus corneas and a novel RCE cell line
      was established in this study. To initiate the primary culture of RCE cells,
      corneas from rabbit eyes were sliced and attached into glutin-coated wells with
      endothelial cell surface down. After being cultured at a time-gradient interval
      from 48 to 6 h, the corneal slices were detached and reattached into new wells,
      respectively. Cells in the wells containing only a pure population of RCE cells
      were collected and cultured in 20% FBS-DMEM/F12 medium containing chondroitin
      sulfate, ocular extract, epidermal growth factor (EGF), basic fibroblast growth
      factor (bFGF), carboxymethyl-chitosan, N-acetylglucosamine hydrochloride,
      glucosamine hydrochloride, culture medium of rabbit corneal stromal cells and
      oxidation-degradation products of chondroitin sulfate at 37 degrees C, 5% CO(2).
      The cultured RCE cells, in quadrangle and polygonal shapes, proliferated to
      confluence 3 weeks later. During the subsequent subculture, the shape of RCE
      cells changed gradually from polygonal to more fibroblastic. A novel RCE cell
      line, growing at a steady rate, with a population doubling time of 53.8 h, has
      been established and subcultured to passage 67. Chromosome analysis showed that
      the RCE cells exhibited chromosomal aneuploidy with the modal chromosome number
      of 44. The results of immuno-cytochemical staining with neuron specific enolase
      (NSE) confirmed that the RCE cells were in neuroectodermal origin. Combined with
      the results of vascular endothelial growth factor (VEGF) treatment and
      endothelial cell morphology recovery, it can be concluded that the cell line
      established here is an RCE cell line. This RCE cell line may serve as a useful
      tool in theoretical researches of mammalian corneal endothelial cells, and may
      also have potential application in artificial corneal endothelium development.

PMID- 17447023
TI  - Distribution of alpha-D-mannose residues on zona pellucida and their role(s) in
      fertilization in pigs.
AB  - The present study aims to identify the distribution of alpha-D-mannose residues
      on zona pellucida (ZP) and their role(s) in fertilization in pigs. In experiment
      1, in vitro matured pig oocytes were freed from cumulus cells and treated with
      fluorescein isothiocyanate-labelled Lens culinaris (FITC-LCA), a D-mannose
      specific binding lectin. After 30 min of treatment, LCA bound evenly throughout
      the ZP with strong fluorescence. In experiment 2, when LCA-treated oocytes were
      used for in vitro fertilization, the number of sperm bound to ZP was
      significantly decreased, and sperm penetration was almost completely blocked. In
      experiment 3, polysaccharide mannan was added to the in vitro fertilization
      medium as a competitive inhibitor. Both the number of sperm bound to ZP and the
      rate of fertilized oocytes were significantly reduced in the mannan-treated group
      compared with the control group. In experiment 4, spermatozoa were incubated with
      mannan in vitro. The number of acrosome-reacted spermatozoa was evidently
      increased in a time-dependent manner during the incubation. These results suggest
      that alpha-D-mannose residues presenting on pig ZP might be an important
      component of sperm receptor and might induce sperm acrosome reaction and thus
      facilitate the sperm penetration into the ZP.

PMID- 17447024
TI  - Effects of different states of sheep fetal fibroblasts as donor cells on the
      early development in vitro of reconstructed sheep embryos.
AB  - To investigate the effects of different states of donor cells on the development
      of reconstructed sheep embryos, we designed five treatments of donor cells,
      including cell passage, cell size, serum starvation, colchicine treatment and
      gene transfection. Results are as follows: (I) Compared with 16-18 passage cells,
      the morula/blastocyst rate of 5-7 passage cells as donor nuclei was significantly
      higher (17.3% vs. 4.9%, P<0.05), suggesting the advantage of short-time cultured
      cells in supporting the development of reconstructed embryos. (II) The
      mourla/blastocyst rate of reconstructed embryos derived from medium cells (15-25
      microm) as donor nuclei was higher than that from large cells (25-33 microm) and
      small cells (8-15 microm)(20.0% vs. 8.0%, 9.7%), indicating that reconstructed
      embryos from medium cells had a greater potentiality to develop into
      morula/blastocysts than those from small or large ones. (III) The
      morula/blastocyst rate of reconstructed embryos from donor cells of SS (serum
      starvation) was lower than that from donor cells of NSS (non-serum starvation),
      but no significant difference was detected between SS and NSS(11.8% vs. 18.6%,
      P>0.05). (IV) Fetal fibroblasts treated with 0.05 micromol/L colchicine exhibited
      a higher morula/blastocyst rate of reconstructed embryos than those treated with
      0.10 micromol/L colchicine and untreated ones (27.5% vs. 12.1%, 17.1%), however,
      no significant difference among the three treatments was detected (P>0.05). (V)
      The morula/blastocyst rate of reconstructed embryos from fetal fibroblasts
      transfected with GFP gene only was 3.1%, significantly lower than that from non
      transgenic cells (3.1% vs. 20.4%, P<0.05). In conclusion, our results
      demonstrated that fetal fibroblasts of fewer passages, medium size could ensure a
      higher morula/blastocyst rate of reconstructed embryos. Serum starvation of donor
      cells might be unnecessary to the development of reconstructed embryos. Donor
      cells treated with 0.05 micromol/L colchicine could facilitate the development of
      reconstructed embryos. Additionally, as cells transfected with GFP gene were used
      as donor nuclei, adverse effect on the development of reconstructed embryos was
      observed. Therefore, the developmental efficiency of reconstructed embryos could
      be improved if proper treatments to donor cells were used.

PMID- 17447025
TI  - Establishment of the diploid gynogenetic hybrid clonal line of red crucian carp x
      common carp.
AB  - This study investigated the gynogenetic cytobiological behavior of the third
      gynogenetic generation (G(3)), which was generated from the diploid eggs produced
      by the second gynogenetic generation (G(2)) of red crucian carp x common carp,
      and determined the chromosomal numbers of G(3), G(2)xscatter scale carp and
      G(2)xallotetraploid hybrids of red crucian carp x common carp. The results showed
      that the diploid eggs of G(2) with 100 chromosomes, activated by UV-irradiated
      sperm from scatter scale carp and without the treatment for doubling the
      chromosomes, could develop into G(3) with 100 chromosomes. Similar to the first
      and second gynogenetic generations (G(1) and G(2)), G(3) was also diploid
      (2n=100) and presented the hybrid traits. The triploids (3n=150) and tetraploids
      (4n=200) were produced by crossing G(2) with scatter scale carp, and crossing
      G(2) with allotetraploids, respectively. The extrusion of the second polar body
      in the eggs of G(2) ruled out the possibility that the retention of the second
      polar body led to the formation of the diploid eggs. In addition, we discussed
      the mechanism of the formation of the diploid eggs generated by G(2). The
      establishment of the diploid gynogenesis clonal line (G(1), G(2) and G(3))
      provided the evidence that the diploid eggs were able to develop into a new
      diploid hybrid clonal line by gynogenesis. By producing the diploid eggs as a
      unique reproductive way, the diploid gynogenetic progeny of allotetraploid
      hybrids of red crucian carp x common carp had important significances in both
      biological evolution and production application.

PMID- 17447026
TI  - Identification of new centrosome proteins by autoimmune patient sera.
AB  - Compared to other subcellular organelles, centrosome proteome can hardly be
      studied, due to the difficulties in separation and purification of centrosome.
      Auto-antisera from 6 autoimmune patients, which recognized centrosome
      specifically in immunofluorescence, were used to identify the corresponding
      centrosomal proteins. The sera were first tested by Western blot on whole cell
      lysate, and all bound antibodies were then eluted from each single band in
      Western blot membrane to assure which antibody was responsible for the centrosome
      specific immunofluorescence staining. The corresponding proteins were obtained by
      immunoprecipitation and identified by mass spectrometry. Six centrosomal
      proteins, including 2 known centrosomal proteins and 4 proteins with unknown
      localization or reportedly non-centrosomal localization, were identified. These
      proteins apparently involve in cell cycle regulation, signal transduction
      pathways, molecular chaperons, and metabolism enzymes, which may reflect the
      expected functional diversity of centrosome.

PMID- 17447027
TI  - Peptide-specific, allogeneic T cell response in vitro induced by a self-peptide
      binding to HLA-A2.
AB  - The role of the bound peptide in alloreactive T-cell recognition is
      controversial, ranging from peptide-independent to peptide-specific recognition
      of alloreactive T-cells. The aim of this study is to find the evidence that there
      exist peptide/MHC complex (pMHC)-specific CTLs among alloreactive T cells
      generated with long-term mixed lymphocytes culture (LTMLC). A single pMHC was
      manipulated by loading the TAP-defective, HLA-A2 expressing T2 cells with a viral
      peptide (LMP2A(426-434)) or a self-peptide (Tyr(369-377)). The PBLs samples from
      4 HLA-A2 positive (HLA-A2+ve) and 4 HLA-A2 negative (HLA-A2-ve) donors were
      included in this study. The HLA-A2+ve PBL co-cultured with the LMP2A(426-434)
      pulsed T2 (T2/LMP) stands for the nominal T-cell response to a viral antigen, and
      the HLA-A2-ve PBLs co-cultured with the Tyr(369-377) pulsed T2 (T2/Tyr) for
      alloreactive T-cell response to an allogeneic antigen. The specificity of the
      expanded CTLs after the LTMLC was detected by their specific cytotoxicity and
      binding ability to specific pMHC-tetramer. An HLA-A2 restricted, HIV peptide
      (Gag(77-85)) was included for control. The cultural bulk of HLA-A2+ve PBLs with
      the T2/LMP showed an elevated specific cytotoxicity against the T2/LMP compared
      to that against the T2/HIV (26.52%+/-3.72% vs 7.01%+/-0.87%, P<0.001), and an
      increased frequency of binding to LMP-tetramer compared to that binding to HIV
      tetramer (0.98%+/-0.33% vs 0.05%+/-0.01%, P=0.0014). The cultural bulk of HLA-A2
      ve PBLs with the T2/Tyr showed a more active cytotoxicity against the T2/Tyr than
      that against T2/HIV (28.07%+/-2.58% vs 6.87%+/-1.01%, P<0.001), and a higher
      frequency of binding to the Tyr-tetramer than that binding to the HIV-tetramer
      (0.88%+/-0.3% vs 0.06%+/-0.03%, P=0.0018). Our results indicate that the LTMLC is
      able to expand the viral antigen-specific CTLs as well as allogeneic antigen
      specific CTLs. A relatively large proportion of alloreactive CTLs should be pMHC
      specific, i.e., the specificity of the alloreactive lines depends on both the
      bound peptide and the allotype of MHC. Our observations support the hypothesis
      that the cumulative effect of T cells specific to each peptide epitope could
      account for the strength and diversity of the alloresponse. The method using
      manipulated pMHC and the LTMLC to generate pMHC-specific, alloreactive CTLs is of
      potential importance for adoptive T-cell immunotherapy.

PMID- 17447028
TI  - Construction and characterization of a recombinant fowlpox virus containing HIV-1
      multi-epitope-p24 chimeric gene in mice.
AB  - The epidemic of HIV/AIDS is sweeping across the world. It is of great importance
      to figure out new ways to curb this disease. Epitope-based vaccine is one of
      these solutions. In this study, a chimeric gene was obtained by combination of a
      designed HIV-1 multi-epitope gene (MEG) and HIV-1 p24 gene. A recombinant plasmid
      pUTA2-MEGp24 was then constructed by inserting MEGp24 gene into the downstream of
      the promoter (ATI-P7.5x20) of fowlpox virus (FPV) transfer vector pUTA2. The
      recombinant plasmid and wild-type FPV 282E4 strain were then co-transfected into
      CEF cells and homologous recombination occurred. A recombinant virus expressing
      HIV-1 protein MEGp24 was screened by genome PCR and Western blot assay. Large
      scale preparation and purification of the recombinant fowlpox virus (rFPV) were
      then carried out. BALB/c mice were immunized intramuscularly with the rFPV for
      three times on day 0, 14 and 42. Mice were executed and sampled one week after
      the third inoculation. Anti-HIV-1 antibody in serum and Th1 cytokines in the
      supernatant of cultured spleen cells were assayed by ELISA. The count of T
      lymphocyte subsets and the CTL activity of spleen lymphocytes were analyzed by
      flow cytometry and lactate dehydrogenase (LDH) release assay, respectively. The
      results showed that HIV-1 specific antibody in serum and increased T lymphocyte
      subsets (CD4(+) T, CD8(+) T) were detected in the immunization group. CTL target
      killing activity and higher secretion of Th1 cytokines (IFN-gamma and IL-2) of
      spleen lymphocytes stimulated by H-2(d)-restricted CTL peptide were observed in
      immunized mice. We concluded that the rFPV may induce HIV-1 specific immunity
      especially cellular immunity in mice.

PMID- 17447029
TI  - Cloning, expression and protective immunity evaluation of the full-length cDNA
      encoding succinate dehydrogenase iron-sulfur protein of Schistosoma japonicum.
AB  - 1071-bp fragment was obtained from the Schistosoma japonicum (Chinese strain)
      adult cDNA library after the 3' and 5' ends of the incomplete expression sequence
      tag (EST) of succinate dehydrogenase iron-sulfur protein of Schistosoma japonicum
      (SjSDISP) were amplified by the anchored PCR with 2 pairs of primers designed
      according to the EST of SjSDISP and the sequence of multiclone sites of the
      library vector. Sequence analysis indicated that the fragment was a full-length
      cDNA with a complete open reading frame (ORF), encoding 278 amino acid residues.
      The fragment was cloned into prokaryotic expression vector pQE30, and
      subsequently sequenced and expressed in Escherichia coli. SDS-PAGE and Western
      blot analyses showed that the recombinant protein was about 32 kD and could be
      recognized by the polyclonal antisera from rabbits immunized with Schistosoma
      japonicum adult worm antigen. Compared with the FCA controls, mice vaccinated
      with rSjSDISP (test) or rSjGST (positive control) all revealed high levels of
      specific antibody and significant reduction in worm burden, liver eggs per gram
      (LEPG), fecal eggs per gram (FEPG) and intrauterine eggs. These results suggest
      that SjSDISP may be a novel and partially protective vaccine candidate against
      schistosomiasis. In contrast to the worm burden reduction rate, the higher degree
      of egg reduction rate in the test group also suggested that SjSDISP vaccine may
      primarily play a role in anti-embryonation or anti-fecundity immunity.

PMID- 17447030
TI  - A rhizobia strain isolated from root nodule of gymnosperm Podocarpus
      macrophyllus.
AB  - Symbiotic nitrogen fixation of rhizobia and leguminous plants is considered as
      the most important biologic nitrogen fixation system on earth. Symbiotic
      nodulation of gymnosperm Podocarpus macrophyllus and rhizobia has never been
      reported. In this study, 11 endophytic bacteria strains were isolated from root
      nodules of P. macrophyllus and its variation P. macrophyllus var. maki. The plant
      infection tests on these strains indicated that the isolated strains could be
      nodulated on P. macrophyllus plants, and weak nitrogenase activity of nodules was
      found in acetylene reduction method. According to the physiological and
      biochemical characteristics of the 11 strains, GXLO 02 was selected as the
      representative strain. 16S rDNA full-length sequence analysis of GXLO 02
      confirmed that the representative strain GXLO 02 belongs to Rhizobium sp.

PMID- 17447031
TI  - Enhancing terpenoid indole alkaloid production by inducible expression of
      mammalian Bax in Catharanthus roseus cells.
AB  - Bax, a mammalian pro-apoptotic member of the Bcl-2 family, triggers
      hypersensitive reactions when expressed in plants. To investigate the effects of
      Bax on the biosynthesis of clinically important natural products in plant cells,
      we generate transgenic Catharanthus roseus cells overexpressing a mouse Bax
      protein under the beta-estradiol-inducible promoter. The expression of Bax in
      transgenic Catharanthus roseus cells is highly dependent on beta-estradiol
      concentrations applied. Contents of catharanthine and total terpenoid indole
      alkaloid of the transgenic cells treated with 30 micromol/L beta-estradiol are
      5.0-and 5.5-fold of the control cells. Northern and Western blotting results show
      that expression of mammalian Bax induces transcriptional activation of Tdc and
      Str, two key genes in terpenoid indole alkaloid biosynthetic pathway of
      Catharanthus roseus cells, and stimulates the accumulation of defense-related
      protein PR1 in the cells, showing that the mouse Bax triggers the defense
      responses of Catharanthus roseus cells and activates the terpenoid indole
      alkaloid biosynthetic pathway. Thus, our data suggest that the mammalian Bax
      might be a potential regulatory factor for secondary metabolite biosynthesis in
      plant cells and imply a new secondary metabolic engineering strategy for
      enhancing the metabolic flux to natural products by activating the whole
      biosynthetic pathway rather than by engineering the single structural genes
      within the pathways.

PMID- 17447032
TI  - GISH and BAC-FISH study of apomictic Beta M14.
AB  - Apomixis is a means of asexual reproduction by which plants produce embryos
      without fertilization and meiosis, therefore the embryo is of clonal and maternal
      origin. Interspecific hybrids between diploid B. vulgaris (2n=2x=18) and
      tetraploid B. corolliflora (2n=4x=36) were established, and then back-crossed
      with B. vulgaris. Among their offspring, monosomic addition line M14 (2n=2x=18+1)
      was selected because of the apomictic phenotype. We documented chromosome
      transmission from B. corolliflora into M14 by using genomic in situ hybridization
      (GISH). Suppression of cross-hybridization by blocking DNA was not necessary,
      indicating that the investigated Beta genome contains sufficient species-specific
      DNA, thus enabling the determination of genomic composition of the hybrids. We
      analyzed BAC microarrays of B. corolliflora chromosome 9 by using fluorescence
      specific mRNA of B. vulgaris and Beta M14. BAC clones 16-M11 and 26-L15 were
      detected as fluorescence-specifics of BAC DNA of Beta M14. Then both BAC clones
      16-M11 and 26-L15 were in situ hybridized to M14 chromosomes. The two hybridized
      BAC clones were located close to the telomere region of the long arm of a single
      chromosome 9, and showed hemizygosity. The results of BAC microarrays showed that
      these developments of embryo and endosperm have conservative expression patterns,
      indicating that sexual reproduction and apomixis have an interrelated pathway
      with common regulatory components and that the induction of a modified sexual
      reproduction program may enable the manifestation of apomixis in Beta species. It
      would be sufficient for the expression of apomixes with those apomictic-specific
      genes on chromosome 9 of B. corolliflora.

PMID- 17447033
TI  - New selenoproteins identified in silico from the genome of Anopheles gambiae.
AB  - Selenoprotein is biosynthesized by the incorporation of selenocysteine into
      proteins, where the TGA codon in the open reading frame does not act as a stop
      signal but is translated into selenocysteine. The dual functions of TGA result in
      mis-annotation or lack of selenoproteins in the sequenced genomes of many
      species. Available computational tools fail to correctly predict selenoproteins.
      Thus, we developed a new method to identify selenoproteins from the genome of
      Anopheles gambiae computationally. Based on released genomic information, several
      programs were edited with PERL language to identify selenocysteine insertion
      sequence (SECIS) element, the coding potential of TGA codons, and cysteine
      containing homologs of selenoprotein genes. Our results showed that 11365 genes
      were terminated with TGA codons, 918 of which contained SECIS elements.
      Similarity search revealed that 58 genes contained Sec/Cys pairs and similar
      flanking regions around in-frame TGA codons. Finally, 7 genes were found to fully
      meet requirements for selenoproteins, although they have not been annotated as
      selenoproteins in NCBI databases. Deduced from their basic properties, the newly
      found selenoproteins in the genome of Anopheles gambiae are possibly related to
      in vivo oxidation tolerance and protein regulation in order to interfere with
      anopheles' vectorial capacity of Plasmodium. This study may also provide
      theoretical bases for the prevention of malaria from anopheles transmission.

PMID- 17447034
TI  - Latency represents sound frequency in mouse IC.
AB  - Frequency is one of the fundamental parameters of sound. The frequency of an
      acoustic stimulus can be represented by a neural response such as spike rate,
      and/or first spike latency (FSL) of a given neuron. The spike rates/frequency
      function of most neurons changes with different acoustic amplitudes, whereas
      FSL/frequency function is highly stable. This implies that FSL might represent
      the frequency of a sound stimulus more efficiently than spike rate. This study
      involved representations of acoustic frequency by spike rate and FSL of central
      inferior colliculus (IC) neurons responding to free-field pure-tone stimuli. We
      found that the FSLs of neurons responding to characteristic frequency (CF) of
      sound stimulus were usually the shortest, regardless of sound intensity, and that
      spike rates of most neurons showed a variety of function according to sound
      frequency, especially at high intensities. These results strongly suggest that
      FSL of auditory IC neurons can represent sound frequency more precisely than
      spike rate.

PMID- 17447035
TI  - Conservation needs of amphibians in China: a review.
AB  - The conservation status of all the amphibians in China is analyzed, and the
      country is shown to be a global priority for conservation in comparison to many
      other countries of the world. Three Chinese regions are particularly rich in
      amphibian diversity: Hengduan, Nanling, and Wuyi mountains. Salamanders are more
      threatened than frogs and toads. Several smaller families show a high propensity
      to become seriously threatened: Bombinatoridae, Cryptobranchidae, Hynobiidae and
      Salamandridae. Like other parts of the world, stream-breeding, high-elevation
      forest amphibians have a much higher likelihood of being seriously threatened.
      Habitat loss, pollution, and over-harvesting are the most serious threats to
      Chinese amphibians. Over-harvesting is a less pervasive threat than habitat loss,
      but it is more likely to drive a species into rapid decline. Five conservation
      challenges are mentioned with recommendations for the highest priority research
      and conservation actions.

PMID- 17447036
TI  - Changes in biodiversity and ecosystem function during the restoration of a
      tropical forest in south China.
AB  - Tropical forests continue to vanish rapidly, but few long-term studies have ever
      examined if and how the lost forests can be restored. Based on a 45-year
      restoration study in south China, we found that a tropical rain forest, once
      completely destroyed, could not recover naturally without deliberate restoration
      efforts. We identified two kinds of thresholds that must be overcome with human
      ameliorative measures before the ecosystem was able to recover. The first
      threshold was imposed primarily by extreme physical conditions such as
      exceedingly high surface temperature and impoverished soil, while the second was
      characterized by a critical level of biodiversity and a landscape context that
      accommodates dispersal and colonization processes. Our three treatment catchments
      (un-restored barren land, single-species plantation, and mixed-forest stand)
      exhibited dramatically different changes in biodiversity and ecosystem
      functioning over 4 decades. The mixed forest, having the highest level of
      biodiversity and ecosystem functioning, possesses several major properties of
      tropical rain forest. These findings may have important implications for the
      restoration of many severely degraded or lost tropical forest ecosystems.

PMID- 17447037
TI  - [Esophageal carcinoma].
AB  - Esophageal cancer is more than ever a surgical problem. Modern diagnostic
      procedures facilitate individual staging, and risk analysis is important for
      adequate patient selection. Using both allows an individualized indication. Under
      multimodal therapeutic protocols, neoadjuvant treatment can best be evaluated and
      is recommended in locally advanced tumors: RCTx in SCC, and CTx in Barrett
      cancer. Here the Ivor-Lewis procedure is the surgical method of choice.
      Postoperative complications are always possible, but the management now is
      standardized and has largely decreased mortality.

PMID- 17447038
TI  - [Two rarely seen manifestations of malignant melanoma].

PMID- 17447039
TI  - [Mid-dermal elastolysis].

PMID- 17447040
TI  - [Transformation of pemphigus foliaceus into pemphigus vulgaris].

PMID- 17447041
TI  - [Pyogenic arthritis, pyoderma gangrenosum and acne syndrome (PAPA syndrome)].

PMID- 17447042
TI  - [Collodium baby: nonbullous congenital ichthyosiform erythroderma].

PMID- 17447043
TI  - [Cutaneous leishmaniasis].
AB  - Infections with Leishmania are increasing worldwide because of tourism and job
      related travel; central Europe is no exception. Infections often first become
      apparent after return from an endemic region. Depending on the Leishmania species
      and the host immune status, different forms of cutaneous (CL), mucocutaneous
      (MCL) (L. brasiliensis complex) or visceral leishmaniasis (L. donovani as well as
      L. infantum) may develop. CL may heal spontaneously with scarring but can evolve
      into diffuse CL (with reduced immune response to L. amazonensis, L. guyanensis,
      L. mexicana or L. aethiopica) or into recurrent CL. Diagnostic criteria include
      travel to an endemic area as well as ulcerated plaques or nodules on an exposed
      site which show no tendency towards healing over 3-4 weeks. Differential
      diagnostic considerations include ecthyma, other infectious ulcers, and malignant
      neoplasms. The diagnosis is confirmed by finding Leishmania in a smear or tissue
      biopsy, as well as by culture. Therapy options range from topical treatment of
      simple CL of the Old World caused by L. major to systemic therapy which is needed
      for most complex cases of CL as well as MCL. Miltefosine is a less toxic option
      to replace the antimony compounds.

PMID- 17447044
TI  - Endocannabinoids, just a gut feeling.

PMID- 17447046
TI  - [Classification and documentation of diffuse gliomas].
AB  - Most current grading systems of diffuse gliomas are based solely on the
      microscopic evaluation of surgical specimens and the TNM classification does not
      have a value for brain tumors. Here additional parameters are presented, which
      are suitable for a classification and documentation of diffuse gliomas. As
      additional parameters to the WHO typing and grading we discuss age groups,
      different tumor devolutions, circumstances such as a second malignant neoplasm or
      hereditary tumors, tumor expansion based on anatomically defined brain regions,
      Karnofsky Scale, eloquence of the brain regions, diag-nostic certainty and
      informativity of tissue samples. This work shows that clinical data and imaging
      studies can contribute substantially to the classification of diffuse gliomas.
      The additional parameters presented here constitute a significant improvement of
      glioma documentation. Especially complex courses of long duration and repeated
      therapeutic interventions can be better surveyed and digitally processed.

PMID- 17447045
TI  - Local administration of WIN 55,212-2 reduces chronic granuloma-associated
      angiogenesis in rat by inhibiting NF-kappaB activation.
AB  - Chronic inflammation is often associated with granuloma formation that is a
      hallmark of many human diseases. The transcription factor nuclear factor-kappa B
      (NF-kappaB) plays a central role in this process by regulating the expression of
      several pro-inflammatory genes. Cannabinoids (CBs) from Cannabis sativa L. exert
      a large number of biological effects including anti-inflammatory and anti
      angiogenic effects. In this study, we investigated the role of CBs on granuloma
      formation induced by lambda-carrageenin-soaked sponge implant in rat. Our results
      show that local administration of WIN 55,212-2, a CB(1)/CB(2) agonist, given
      daily or at time of implantation significantly decreased weight and neo
      angiogenesis in granuloma tissue and inhibited nuclear factor-kappa B (NF
      kappaB)/DNA binding that was associated with a reduced inducible nitric oxide
      synthase (iNOS), cyclooxygenase 2 (COX-2), tumor necrosis factor alpha (TNF
      alpha), and vascular endothelial growth factor (VEGF) messenger RNA (mRNA) and
      protein expression. Also, arachidonyl-2-chloroethylamide (ACEA), a CB(1)
      selective agonist, and JWH-015, a CB(2) selective agonist, exhibited the same
      effects that were reversed by SR141716-A and SR144528, respectively, CB(1) and
      CB(2) selective antagonists. These results indicate that CBs given locally may
      represent a potential therapeutic tool in controlling chronic inflammation
      avoiding psychotropic effects.

PMID- 17447047
TI  - [Primary prevention, health promotion, and compression of morbidity. Perspectives
      for urology].
AB  - Prevention and health promotion are interventions which achieve compression of
      morbidity. This is well-advised from the viewpoints of both health economics and
      quality of life in an aging society. Only when preventive and health-promoting
      strategies have become a matter of course in the health care system can the
      challenges posed by the altered disease spectrum be met. Because of the frequency
      of age-associated diseases encountered in urological practice and the
      considerable influence it wields on quality of life, urology is a focus of
      attention. Prevention and health counseling will prove to be major tasks in the
      practice of urology, especially in the private sector. Viewed systematically,
      primary prevention is more medical and individual in character while health
      promotion is an aspect of health science geared toward a specific echelon or
      group. The mission of health policy and medical associations must be to design
      and evaluate programs for prevention and health promotion. This is uncharted
      territory for urology. Economic aspects specific to professional groups should
      not constitute the sole center of attention, even though these interests are
      legitimate. It is essential that the approach to primary prevention efforts be
      directed at specific echelons and groups to also reach fringe groups and socially
      weak groups in the population.

PMID- 17447048
TI  - [Secondary prevention after urological cancers. What are the pertinent facts
      about aftercare?].
AB  - Secondary prevention and aftercare of urological cancers are an essential part of
      outpatient care provided by the urologist in private practice. More than one-half
      of the patients who are confronted with the diagnosis of cancer turn to so-called
      unconventional treatment procedures. The difficulties for those affected and
      caregivers lie in equal measure in distinguishing between sensible and less
      advisable or even counterproductive treatment options. Fixed plans of action for
      aftercare do not do justice to the exigencies of individualized care of cancer
      patients in private practice, especially with respect to longer survival. Early
      detection of local recurrence and metastases and the management of complications
      are determined by the individual disease course and have to be measured against
      the improvement in quality of life. Secondary preventive measures in the sense of
      complementary medicine can be helpful. Current evidence is quite promising only
      for prostate cancer and is of some importance in urological practice.

PMID- 17447050
TI  - Spatio-temporal genetic variation in populations of wild emmer wheat, Triticum
      turgidum ssp. dicoccoides, as revealed by AFLP analysis.
AB  - Genetic structure of natural populations of wild crop relatives has been the
      subject of many studies. Yet, most of them focused on the assessment of spatial
      genetic diversity, while information on long-term variation, affected by yearly
      changes, has been considered only in few cases. The present study aimed
      therefore, to estimate the spatio-temporal genetic variation in populations of
      wild emmer wheat, the progenitor of domesticated wheat, and to assess the
      contribution of spatial versus temporal factors to the maintenance of genetic
      variation in a population. Single spikes were collected in the years 1988 and
      2002 from plants that grew in the same sampling points, from six different
      habitats in the Ammiad conservation site, Eastern Galilee, Israel. Seeds were
      planted in a nursery and DNA was extracted from each plant and analyzed by the
      AFLP method. Fourteen primer combinations yielded 1,545 bands of which 50.0 and
      48.8% were polymorphic in the years 1988 and 2002, respectively. Genetic
      diversity was much larger within populations than between populations and the
      temporal genetic diversity was considerably smaller than the spatial one.
      Nevertheless, population genetic structure may vary to some degree in different
      years, mainly due to fluctuations in population size because of yearly rainfall
      variations. This may lead to predominance of different genotypes in different
      years. Clustering the plants by their genetic distances grouped them according to
      their habitats, indicating the existence of genotype-environment affinities. The
      significance of the results in relation to factors affecting the maintenance of
      polymorphism in natural populations is discussed.

PMID- 17447049
TI  - [Small incidental renal tumors. Evaluation and biological parameters].
AB  - Tumor size is a prognostic marker and correlates to survival after surgical
      therapy. Of 287 patients with small (<or=4 cm) renal tumors, 19.5% had a benign
      lesion and thus harmless. All others were renal cell cancers; 4.9% of tumors were
      detected because of metastases and consecutively treated. Tumors with a diameter
      <or=3 cm showed a tumor stage >or=pT3a in 10.9%, a high Fuhrman grade >or=3,
      multifocality in 8.5%, and metastases in 2.4%. Tumors with a diameter of 3.1-4 cm
      showed dramatically more aggressive parameters; 35.7% had stage >or=pT3a, 25.5%
      Fuhrman grade >or=G3, and 8.4% metastases (M+). However, evaluation of the tumor
      diameter on CT has an error of about +/-0.3 cm, which will lead to an even more
      pronounced error in volume determination. Therefore, determination of growth in
      follow-up imaging is unreliable. With the exception of the typical
      angiomyolipoma, determination of dignity for small solid kidney lesions is
      unreliable even with modern imaging. Only 17% of 80 benign lesions in our series
      were assessed as benign on preoperative CT. Thus, preoperative evaluation not
      only based on imaging seems to be valuable, especially in patients with higher
      surgical risk. Percutaneous renal mass biopsy has an accuracy of over 90% for
      detecting benign lesions and can influence therapeutic decisions, especially in
      patients with higher surgical risk.

PMID- 17447051
TI  - Time-dependent decreases in apparent pA2 values for naltrexone studied in
      combination with morphine in rhesus monkeys.
AB  - RATIONALE: One assumption of Schild analyses, which have been used extensively to
      characterize opioids in vitro and in vivo, is that the concentration of
      antagonist is at equilibrium; violation of this assumption would yield slopes of
      Schild plots that deviate from unity. For in vivo studies, the concentration of
      antagonist changes as it is eliminated; however, if studies are conducted at a
      time when the antagonist is maximally effective, the assumption of equilibrium is
      not violated. OBJECTIVE: The goal of these studies was to determine how
      increasing the delay between antagonist administration and determination of dose
      effect curves alters results of Schild analyses. MATERIALS AND METHODS: Monkeys
      received 3.2 mg/kg/day of morphine and discriminated naltrexone while responding
      under a fixed-ratio 5 schedule of stimulus-shock termination. In monkeys acutely
      deprived of morphine (27 h), naltrexone was administered 1, 2, 4, or 6 h before
      determination of morphine dose-effect curves. RESULTS: Morphine-deprived monkeys
      responded on the naltrexone-appropriate lever, and this effect was reversed by
      morphine. Naltrexone dose- and time-dependently antagonized morphine. Schild
      analyses yielded slopes that did not deviate from unity; however, as the delay
      between naltrexone administration and determination of morphine dose-effect
      curves increased, apparent pA(2) values decreased. CONCLUSIONS: The assumption of
      equilibrium of antagonist at receptor sites does not appear to be violated,
      regardless of when it is administered, and changes in naltrexone concentration as
      it is eliminated are reflected in orderly decreases in potency. These results
      further indicate the strength of Schild analyses for describing interactions
      between drugs and receptors in vivo.

PMID- 17447052
TI  - A pharmacological analysis of stimulant-induced increases in smoking.
AB  - RATIONALE: Stimulants increase tobacco smoking in healthy adults under controlled
      laboratory conditions. The mechanisms that mediate stimulant-induced increases in
      smoking are not known. OBJECTIVE: The purpose of the present experiment was to
      characterize the pharmacological specificity of stimulant-induced increases in
      smoking. We tested the effects of methylphenidate and atomoxetine on smoking
      behavior. Atomoxetine is a norepinephrine transport inhibitor that does not
      increase dopamine levels in the nucleus accumbens or striatum. If stimulant
      induced increases in smoking result from an additive or synergistic effect of
      these drugs and nicotine on dopamine levels in the nucleus accumbens or striatum,
      methylphenidate but not atomoxetine should increase smoking. MATERIALS AND
      METHODS: Doses of methylphenidate (10, 20, and 40 mg) and atomoxetine (20, 40,
      and 80 mg) were tested once while placebo was tested twice in 12 cigarette
      smokers. One hour after ingesting drug, participants smoked ad libitum for 4 h.
      Measures of smoking included total cigarettes, total puffs, and carbon monoxide
      levels. Snacks and decaffeinated drinks were available ad libitum, and food
      intake was calculated. RESULTS: Methylphenidate but not atomoxetine dose
      dependently increased the number of cigarettes, puffs, and carbon monoxide
      levels. Methylphenidate and atomoxetine decreased food intake. CONCLUSIONS: The
      results of this experiment are consistent with the notion that stimulant-induced
      increases in smoking may result from an additive or synergistic effect of these
      drugs and nicotine on dopamine levels in the nucleus accumbens or striatum.
      Additional research is needed to more fully understand the pharmacological
      mechanisms that mediate the relationship between stimulant use and smoking.

PMID- 17447053
TI  - Sensitive determination of nitric oxide in some rat tissues using polymer
      monolith microextraction coupled to high-performance liquid chromatography with
      fluorescence detection.
AB  - A simple, sensitive, selective, and low-cost method is proposed for rapidly
      determining nitric oxide (NO) in some rat tissues. Polymer monolith
      microextraction (PMME) using a poly(methacrylic acid-ethylene glycol
      dimethacrylate) (MAA-EGDMA) monolithic column was combined with derivatization of
      NO using 1,3,5,7-tetramethyl-8-(3',4'-diaminophenyl)-difluoroboradiaza-s-indacene
      (TMDABODIPY), and this was used to analyze the derivatives of NO by high
      performance liquid chromatography (HPLC) with fluorescence detection at lambda
      (ex)/lambda (em) = 498/507 nm. The baseline separation of TMDABODIPY and its NO
      derivative is performed under simple conditions in which a C(18) column is used
      and eluted with 50 mmol L(-1) ethanolamine and methanol. The conditions for the
      extraction of NO derivatives were optimized. The limit of detection of NO was 2 x
      10(-12) mol L(-1) (S/N = 3). The linearity range of the method was 9 x 10(-11)
      4.5 x 10(-8) mol L(-1). The interday and intraday relative standard deviations
      were less than 5%. The proposed method was successfully applied to the
      determination of NO levels in some rat tissue samples including heart, kidney,
      and liver with recoveries varying from 87.1 to 95.2%.

PMID- 17447054
TI  - Characterization of ganoderma spore lipid by stable carbon isotope analysis:
      implications for authentication.
AB  - The ratios of stable carbon isotopes ((13)C/(12)C) of ganoderma fruiting body,
      ganoderma spore, ganoderma spore lipid (GSL) and individual fatty acids in GSL
      were determined by gas chromatography-stable isotope ratio mass spectrometry and
      elemental analysis-stable isotope ratio mass spectrometry. These values fall into
      a range from -26.9 to -23.3 per thousand, suggesting that the cut log as the
      Ganoderma-cultivated substrate in Fujian, China, may belong to C3 plants.
      Eighteen fatty acids were identified and their abundances measured by gas
      chromatography-mass spectrometry in the six GSL samples with C(16:0), C(18:0),
      C(18:1) and C(18:2) as major constituents, and C(16:1) is evidently enriched
      compared with the other edible vegetable oils. On the basis of the compositions
      of fatty acids and stable carbon isotopes in GSL, we have developed a novel
      method to detect the adulteration of GSL products with cheaper edible vegetable
      oils. An example of ideal blending between GSL and C4 or C3 vegetable oil is
      further provided to expound the discrimination procedures and corresponding
      sensitive indicators. Simultaneously, the carbon isotope fractionation in the
      biosynthesis of individual fatty acids was observed, revealing that the formation
      of C(18:0) from C(16:0) in ganodema spores had no conspicuous (13)C enrichment of
      +0.4 per thousand for Ganoderma sinensis spore and +0.1 per thousand for G.
      lucidum spore; the desaturation of C(18:0) to C(18:1) resulted in a distinct
      (13)C depletion of -1.4 per thousand for G. sinensis spore and -0.9 per thousand
      for G. lucidum spore; and the next desaturation from C(18:1) to C(18:2) displayed
      no evident (13)C fractionation of -0.1 per thousand for G. sinensis spore and 
      0.2 per thousand for G. lucidum spore.

PMID- 17447055
TI  - Identification of human hepatocellular carcinoma-related proteins by proteomic
      approaches.
AB  - Hepatocellular carcinoma (HCC) is the most common malignant liver tumor. Analysis
      of human serum from HCC patients using two-dimensional gel electrophoresis (2DE)
      combined with nano-high-performance liquid chromatography electrospray ionization
      tandem mass spectrometry (nano-HPLC-ESI-MS/MS) identified fourteen different
      proteins differentially expressed between HCC patients and the control group.
      Twelve proteins were up-regulated and two down-regulated. By using nano-HPLC
      MS/MS system to analyze proteome in human serum, 317 proteins were identified,
      twenty-nine of which to high confidence levels (protein matched at last two
      unique peptide sequences). Of these twenty-nine proteins, six were present only
      in HCC patients and may serve as biomarkers for HCC.

PMID- 17447056
TI  - Analgesic use and pain in the hospital settings.
AB  - AIM: The aim of this study was to assess the analgesic treatment and the
      prevalence of pain in patients treated with analgesics in hospitals. METHODS:
      Adult patients treated with analgesics were selected from a sample of 1,675
      patients in a cross-sectional study carried out in 15 Catalonian hospitals
      (Spain). Patient characteristics, type of analgesics, treatment schedules,
      patients' pain intensity and clinical ward and hospital characteristics were
      assessed. Adherence to analgesic use guidelines was established according to the
      principles and recommendations of internationally recognised guidelines for pain
      management. Pain was determined by asking patients about pain intensity by means
      of a visual analogue scale (VAS). RESULTS: Analgesics were prescribed for 1,173
      patients (70%; 95% CI: 67.4-72.6), in whom 57% (95% CI: 54.2-59.8) had pain and
      in whom 30.5% (95% CI: 27.9-33.1) pain intensity was greater than 30 mm.
      Adherence to analgesic treatment guidelines was judged appropriate in only 26.9%
      (95% CI: 24.4-29.4%) of all patients. The administered analgesic dose was in the
      recommended dose range in 42% (95% CI: 54-58) of all analgesics and in 28% (95%
      CI: 24-32) of opioid analgesics. A minority of patients was treated with a rescue
      schedule or patient-controlled analgesia (2%; 95% CI: 1.4-2.6). Pain prevalence
      was higher in those with analgesic treatment that did not adhere to guidelines
      (63.6%; 95% CI: 60.4-66.8) than in those considered as having appropriate
      adherence to guidelines (39.3%; 95% CI: 33.8-44.6) (p < 0.001). Adherence to
      analgesic treatment guidelines was higher in the large hospitals (21%; 95% CI: 18
      24) than in medium and small hospitals (13%; 95% CI: 9-16) (p < 0.001).
      CONCLUSIONS: Although analgesic use is high in the hospital settings, adherence
      to the principles and recommendations of pain guidelines is low, and pain is
      usually common in patients treated with analgesics. These results once again
      emphasise the need to improve analgesic use and pain management in hospitals.

PMID- 17447057
TI  - The impact of radiological anatomy in clearance of lower caliceal stones after
      shock wave lithotripsy.
AB  - The goal of this study was to determine the factors affecting stone clearance
      after extracorporeal shock wave lithotripsy (ESWL) for lower caliceal stones.
      Lower pole stone clearance was investigated in 128 (80 males, 48 females)
      patients treated with ESWL during 1998-2003 in our clinic. Renal anatomy was
      determined on standard intravenous urogram. The lower infundibulopelvic angle
      (LIPA) was measured as the angle between the vertical pelvis axis and the
      vertical axis of lower infundibulum (Sampaio's method). The mean age of the
      patients was 42.8 +/- 12.4 (19-77) years. The mean stone diameter and burden were
      found to be 1.28 +/- 0.58 (0.5-3.5) cm and 1.2 +/- 1 (0-7) cm(2) respectively.
      The stone-free rate was 62.5% and ESWL was unsuccessful in 16 (12.5%) patients.
      Thirty-two (25%) patients had residual fragments < or =4 mm retained in lower
      calices after lithotripsy. The stone clearance was found to be unrelated to stone
      burden and diameter (P = 0.17 and P = 0.14, respectively). However, there was a
      significant difference between mean lower pole infundibulum length (P = 0.001),
      infundibulum width (P = 0.001) and LIPA (P = 0.0001) between stone-free patients
      and patients with residual fragments. Multivariate logistic regression analysis
      accepting stone-free as the favourable result also confirmed that LIPA, lower
      pole infundibulum length and width were factors that significantly affected the
      outcome. Lower pole anatomy has a significant influence on clearance of fragments
      after ESWL.

PMID- 17447058
TI  - Citric acid production from sucrose using a recombinant strain of the yeast
      Yarrowia lipolytica.
AB  - The yeast Yarrowia lipolytica is able to secrete high amounts of several organic
      acids under conditions of growth limitation and carbon source excess. Here we
      report the production of citric acid (CA) in a fed-batch cultivation process on
      sucrose using the recombinant Y. lipolytica strain H222-S4(p67ICL1) T5,
      harbouring the invertase encoding ScSUC2 gene of Saccharomyces cerevisiae under
      the inducible XPR2 promoter control and multiple ICL1 copies (10-15). The pH
      dependent expression of invertase was low at pH 5.0 and was identified as
      limiting factor of the CA-production bioprocess. The invertase expression was
      sufficiently enhanced at pH 6.0-6.8 and resulted in production of 127-140 g l(-1)
      CA with a yield Y (CA) of 0.75-0.82 g g(-1), whereas at pH 5.0, 87 g l (-1) with
      a yield Y (CA) of 0.51 g g(-1) were produced. The CA-productivity Q (CA)
      increased from 0.40 g l (-1) h(-1) at pH 5.0 up to 0.73 g l (-1) h(-1) at pH 6.8.
      Accumulation of glucose and fructose at high invertase expression level at pH 6.8
      indicated a limitation of CA production by sugar uptake. The strain H222
      S4(p67ICL1) T5 also exhibited a gene-dose-dependent high isocitrate lyase
      expression resulting in strong reduction (<5%) of isocitric acid, a by-product
      during CA production.

PMID- 17447059
TI  - Lymphoscintigraphic and intraoperative detection of sentinel lymph nodes.

PMID- 17447060
TI  - PET/CT visualises inflammatory activity of pulmonary artery aneurysms in Behcet
      disease.

PMID- 17447061
TI  - Tumour hypoxia imaging with [18F]FAZA PET in head and neck cancer patients: a
      pilot study.
AB  - PURPOSE: Hypoxia is an important negative prognostic factor for radiation
      treatment of head and neck cancer. This study was performed to evaluate the
      feasibility of use of (18)F-labelled fluoroazomycin arabinoside ([(18)F]FAZA) for
      clinical PET imaging of tumour hypoxia. METHODS: Eleven patients (age 59.6 +/- 9
      years) with untreated advanced head and neck cancer were included. After
      injection of approximately 300 MBq of [(18)F]FAZA, a dynamic sequence up to 60
      min was acquired on an ECAT HR+ PET scanner. In addition, approximately 2 and 4 h
      p.i., static whole-body PET (n = 5) or PET/CT (n = 6) imaging was performed. PET
      data were reconstructed iteratively (OSEM) and fused with CT images (either an
      external CT or the CT of integrated PET/CT). Standardised uptake values (SUVs)
      and tumour-to-muscle (T/M) ratios were calculated in tumour and normal tissues.
      Also, the tumour volume displaying a T/M ratio >1.5 was determined. RESULTS:
      Within the first 60 min of the dynamic sequence, the T/M ratio generally
      decreased, while generally increasing at later time points. At 2 h p.i., the
      tumour SUV(max) and SUV(mean) were found to be 2.3 +/- 0.5 (range 1.5-3.4) and
      1.4 +/- 0.3 (range 1.0-2.1), respectively. The mean T/M ratio at 2 h p.i. was 2.0
      +/- 0.3 (range 1.6-2.4). The tumour volume displaying a T/M ratio above 1.5 was
      highly variable. At 2 h p.i., [(18)F]FAZA organ distribution was determined as
      follows: kidney > gallbladder > liver > tumour > muscle > bone > brain > lung.
      CONCLUSION: [(18)F]FAZA PET imaging appears feasible in head and neck cancer
      patients, and the achieved image quality is adequate for clinical purposes. Based
      on our initial results, [(18)F]FAZA warrants further evaluation as a hypoxia PET
      tracer for imaging of cancer.

PMID- 17447062
TI  - PET detection of epidermal growth factor receptor in colorectal cancer: a real
      predictor of response to cetuximab treatment?

PMID- 17447063
TI  - Role of IL-21 in immune-regulation and tumor immunotherapy.
AB  - IL-21, the most recently discovered member of the IL-2 cytokine family, is an
      attractive subject for research due to its involvement in experimental models of
      autoimmunity, its ability to down-regulate IgE production, and its anti-tumor
      properties. Its interest for cancer immunotherapy stems from its physiological
      immune-enhancing functions. These include regulation of T, B and NK cell
      proliferation, survival, differentiation, and effector functions. IL-21's
      functional activities partially overlap those of IL-2. Both cytokines display
      similar structural features and use the common gamma-chain receptor and its
      downstream signaling pathways. Besides its activities on normal lymphoid cells,
      IL-21 is an in vitro growth factor for myeloma and acute-T cell leukemia cells,
      whereas it induces the apoptosis of B-CLL (chronic lymphocytic leukemia) cells.
      These findings indicate that the IL-21/IL-21R system exerts opposite functions in
      different lymphoid neoplasias, and suggest its employment in B-CLL therapy. Since
      IL-2, but not IL-21, is specifically required for the development of regulatory T
      (Treg) cell immune-suppressive functions, IL-21 may be a new tool for cancer
      immunotherapy. It is, in fact, a powerful anti-tumor agent in a variety of murine
      experimental tumor models through its activation of specific or innate immune
      responses against neoplastic cells. The preliminary data from phase-I clinical
      studies suggest that the use of IL-21 is feasible and may result in immune
      enhancing effects.

PMID- 17447064
TI  - Immunogenicity of the carcinoembryonic antigen derived peptide 694 in HLA-A2
      healthy donors and colorectal carcinoma patients.
AB  - Carcinoembryonic antigen (CEACAM5) is commonly overexpressed in human colon
      cancer. Several antigenic peptides recognized by cytolytic CD8+ T-cells have been
      identified and used in colon cancer phase-I vaccination clinical trials. The HLA
      A*0201-binding CEA(694-702) peptide was recently isolated from acid eluted MHC-I
      associated peptides from a human colon tumor cell line. However, the
      immunogenicity of this peptide in humans remains unknown. We found that the
      peptide CEA(694-702) binds weakly to HLA-A*0201 molecules and is ineffective at
      inducing specific CD8+ T-cell responses in healthy donors. Immunogenic-altered
      peptide ligands with increased affinity for HLA-A*0201 were identified.
      Importantly, the elicited cytolytic T lymphocyte (CTL) lines and clones cross
      reacted with the wild-type CEA(694-702) peptide. Tumor cells expressing CEA were
      recognized in a peptide and HLA-A*0201 restricted fashion, but high-CEA
      expression levels appear to be required for CTL recognition. Finally, CEA
      specific T-cell precursors could be readily expanded by in vitro stimulation of
      peripheral blood mononuclear cell (PBMC) from colon cancer patients with altered
      CEA peptide. However, the CEA-specific CD8+ T-cell clones derived from cancer
      patients revealed low-functional avidity and impaired tumor-cell recognition.
      Together, using T-cells to demonstrate the processing and presentation of the
      peptide CEA694-702, we were able to corroborate its presentation by tumor cells.
      However, the low avidity of the specific CTLs generated from cancer patients as
      well as the high-antigen expression levels required for CTL recognition pose
      serious concerns for the use of CEA694-702 in cancer immunotherapy.

PMID- 17447066
TI  - Extensive leukemic kidney infiltration with membranoproliferative
      glomerulonephritis in a patient with B-cell chronic lymphocytic leukemia.

PMID- 17447065
TI  - Initial stability of circumferential meshes with impacted bone allografts for
      massive femoral defects.
AB  - When the proximal femur is absent due to a failed femoral stem in total hip
      arthroplasty, impacted bone grafts contained within circumferential meshes could
      be an alternative reconstructive method. The purpose of this study was to analyse
      the initial resistance to axial and rotational forces in a fresh frozen bovine
      model with complete loss of the proximal femur reconstructed with a
      circumferential metal mesh, impacted bone allografts and a long cemented stem.
      Four bovine femurs with a complete proximal bone defect were reconstructed with a
      circumferential mesh, impacted bone grafts and a cemented stem. The results were
      compared with four intact femurs using the same implant. Under axial load,
      subsidence was observed at an average of 617 kg in the experimental group, and a
      cortical fracture occured at 1335 kg in the control group. Under rotational load,
      experimental femurs failed at an average of 79 kg and the control femurs
      fractured at 260 kg. This model provided 50% of the resistance to axial load and
      30% of the resistance to rotational load compared to an intact femur, which is
      enough to resist physiological load. This stability encourages the use of
      circumferential meshes, impacted bone allografts and cemented stems in revision
      hip surgery with massive bone loss.

PMID- 17447067
TI  - A comparison of the effectiveness of selected non-steroidal anti-inflammatory
      drugs and their derivatives against cancer cells in vitro.
AB  - PURPOSE: Previously, we reported in vitro observations suggesting that ibuprofen
      is an effective non-prescription non-steroidal anti-inflammatory drug (NSAID) to
      reduce the survival of human prostate cancer cells (Andrews et al. in Cancer
      Chemother Pharmacol 502:77-284, 2002), and that this observed effectiveness is
      mediated by an up-regulation of the p75 NTR tumor suppressor (Khwaja et al. in
      Cancer Res 646:207-6213, 2004). However, other NSAIDs and their derivatives have
      received significant attention with regard to their anti-cancer effectiveness and
      have been selected for clinical trials to treat a variety of human cancers. In
      this investigation, we compared celecoxib, sulindac sulfone, nitric oxide linked
      NSAIDs, and R-flurbiprofen with ibuprofen in their ability to inhibit the growth
      of a variety of human cancer cells lines including cells lines with multi-drug
      resistance. We also evaluated whether, like ibuprofen, an up-regulation of p75
      NTR is a molecular mechanism that mediates the anti-growth effectiveness of these
      drugs. MATERIALS AND METHODS: Selected dosages for each drug were evaluated for
      their ability to reduce the growth (MTT analysis) and induce apoptosis (Hoechst
      staining) of a variety of different cancer cell lines, including an ovarian cell
      line expressing multidrug resistance-1 glycoprotein (MDR-1). The drugs were then
      analyzed using immunoblot, RT-PCR and siRNA to study the role of p75 NTR in their
      anti-growth effectiveness. RESULTS: Our study revealed consistency in the drug
      dosages that inhibit the survival of different human cancer cell lines. While NO
      linked aspirin and celecoxib were most effective in decreasing cell growth and
      inducing apoptosis at the lowest dosages, R-flurbiprofen and ibuprofen were most
      effective at clinically relevant dosages. A multidrug resistant ovarian cell line
      is more resistant to growth inhibition by the drugs tested than its non-drug
      resistant parental counterpart. There was no correlation between the expression
      of cyclooxygenase-2 (COX-2) and the ability of the drugs to reduce cancer cell
      survival. All the drugs tested induced an up-regulation in p75 NTR tumor
      suppressor gene expression in concert with their observed growth inhibiting
      ability. Inhibition of p75 NTR expression with siRNA reduced the cell growth
      inhibiting effects of all the drugs tested. CONCLUSIONS: The method of
      chemotherapy (i.e., intravascular, intrathecal, oral) might dictate the choice of
      NSAID/NSAID derivative used to treat/prevent a given type of cancer. Also, the
      p75 NTR tumor suppressor appears to be a common molecular mechanism that mediates
      the growth inhibiting effectiveness of these drugs.

PMID- 17447068
TI  - [Transitional cell carcinoma of the ovary. Morphological and clinical features].
AB  - Transitional cell carcinoma of the ovary (TCC-O) is a less common type of
      malignant surface epithelial-stromal tumor of the ovary, still with uncertain
      incidence. Histologically, TCC-O resembles urothelial carcinoma of the urinary
      system, and by definition does not contain a Brenner tumor component. TCC-O may
      not be a bona fide urothelial neoplasm, however, but rather a lesion of the
      Mullerian type derived from the ovarian surface epithelium. This notion is
      supported by the existence of mixed tumors consisting of TCC-O and other
      histological types of ovarian carcinoma, as well as the observation that TCC-O
      has a Mullerian type but not a urothelial-like immunohistochemical profile.
      Besides metastatic urothelial carcinoma of the urinary tract, the other types of
      ovarian carcinoma, as well as sex cord-stromal tumors such as adult granulosa
      cell tumors, have to be considered in the differential diagnosis of TCC-O. A
      recent analysis of a large series of advanced ovarian carcinomas treated by
      radical surgery and postoperative chemotherapy confirms studies that had
      suggested that TCC-O has a better prognosis (with current treatment) than that of
      the other histological types of ovarian carcinoma. Further studies applying
      standardized histopathological criteria are needed to clarify the true incidence
      and behavior of TCC-O. In addition, it is important to study the biological and
      molecular background of this apparently less aggressive phenotype.

PMID- 17447069
TI  - Diagnostic performances of anti-cyclic citrullinated peptide antibodies in
      rheumatoid arthritis.
AB  - To evaluate the rheumatoid arthritis (RA) diagnostic performances of anti-cyclic
      citrullinated peptide antibodies (anti-CCP). Anti-CCP was detected by an enzyme
      linked immunosorbent assay in 164 patients with RA and 343 controls. In addition,
      anti-CCP predictive value for radiological damage were investigated in 37 recent
      onset RA patients followed up prospectively for 2 years. Radiological damages
      were assessed by Sharp method modified by van der Heijde. The sensitivity of anti
      CCP was 78.7% and the specificity was 95.6%. The positive predictive value and
      the negative predictive value were 90.2% and 90.3%, respectively. Anti-CCP were
      detected in sera of 79.3% of patients with recent onset RA and 78.3% of patients
      with long disease duration. In univariate and multivariate analyses, anti-CCP
      were not predictive for radiological damage. Our study confirms the high
      diagnostic performances of anti-CCP in RA. They are very useful to aid the
      diagnostic of RA in clinical practice.

PMID- 17447070
TI  - High-resolution ultrasound of peripheral neurogenic tumors.
AB  - Peripheral nerve tumors are not frequent, but due to their association with a
      nerve they are somewhat special. They may be encountered incidentally during
      evaluation of a soft-tissue mass or when a nerve lesion is clinically suspected
      and the recognition of such a lesion and its differential diagnosis is key for
      successful therapy and patient prognosis. As sonography is often the first line
      modality in the work-up of a soft-tissue mass, the sonographer should be aware of
      the typical features of such lesions in order to arrive at the correct diagnosis,
      and this article tries to give an overview of the histological subtypes of
      peripheral nerve tumors and their sonographic characteristics.

PMID- 17447071
TI  - Secretin-stimulating MRCP in patients with pancreatobiliary maljunction and
      occult pancreatobiliary reflux: direct demonstration of pancreatobiliary reflux.
AB  - We propose the hypothesis that the enlargement of the common bile duct (CBD) or
      gallbladder (GB) that is occasionally demonstrated on magnetic resonance
      cholangiopancreatography (MRCP) after secretin stimulation is caused by
      pancreatobiliary reflux. Recently, occult pancreatobiliary reflux (OPR) has been
      demonstrated in patients without morphological pancreatobiliary maljunction
      (MPBM). The aim of this study was to evaluate the efficacy of secretin
      stimulating MRCP (SMRCP) in the diagnosis of pancreatobiliary reflux. The study
      included 14 patients with MPBM and 32 patients with a normal pancreatobiliary
      junction. OPR was evaluated by bile collection and diagnosed in seven of the 32
      patients. All the patients underwent SMRCP; the related findings were considered
      positive when enlargement of the CBD or GB was observed. Positive findings on
      SMRCP were observed in all MPBM patients. In the patients with normal
      pancreatobiliary junction, there was significant difference between the mean
      amylase levels in the patients with positive and negative SMRCP findings (mean,
      4,755.7 and 29.7 IU/l). The sensitivity and specificity of SMRCP for diagnosing
      OPR was 85.7% and 68.0%, respectively. SMRCP provides a non invasive method for
      excluding PBR and can identify patients who could benefit from bile duct sampling
      to diagnose OPR.

PMID- 17447072
TI  - [Adenoid cystic carcinoma of the upper eyelid].
AB  - Adenoid cystic carcinoma (ACC) is a rare epithelial malignancy, which tends to
      grow slowly. ACC is an intractable neoplasm due to its ability to invade
      perineural spaces. Local recurrence after excision is not unusual. ACC most
      commonly arises in the lacrimal gland. Very rarely, ACC originates from accessory
      lacrimal gland tissue. Here, we present a patient with a large ACC of the central
      upper eyelid, which had been misdiagnosed and treated as a chalazion without
      histological examination. Its origin most likely is an accessory lacrimal gland.

PMID- 17447073
TI  - Hypothalamic hamartoma with bilateral anophthalmia.
AB  - INTRODUCTION: Hypothalamic hamartomas are congenital malformations. Clinically,
      they can be asymptomatic, but they cause seizures, mental retardation and
      precocious puberty in many cases. CASE REPORT: A 20-day-old boy with hypothalamic
      hamartoma and bilateral anophthalmia was presented. Except those, no other
      congenital anomaly was detected. CONCLUSION: This is a rare case of hypothalamic
      hamartoma with bilateral anophthalmia. The mutations at SOX2 has an important
      role in the developing brain and eyes.

PMID- 17447074
TI  - Complications following endoscopic intracranial procedures in children.
AB  - BACKGROUND: The significant technological improvement of endoscopic
      instrumentation has allowed, in the last 10 years, a widespread diffusion of
      neuroendoscopic procedures. Nevertheless, severe, sometimes life-threatening,
      complications may occur during neuroendoscopic surgery, and the incidence and age
      specificity of complications in children have been underdescribed so far.
      MATERIALS AND METHODS: Complications recorded in a prospectively collected
      database of pediatric patients undergoing neuroendoscopic procedures were
      analysed; the medical histories of the patients and the surgical procedures were
      reviewed. RESULTS: Complications occurred in 32 out of 231 (13.8%) procedures
      performed for the management of obstructive hydrocephalus (137), multiloculated
      hydrocephalus (53), arachnoid cysts (29) and intraventricular tumors (12).
      Subdural hygroma occurred in 11 cases, seven requiring subdural shunting. In one
      of these cases, infection of the subdural space occurred and required a
      craniotomy. Cerebrospinal fluid (CSF) infection occurred in 11 cases. In one
      case, a frontal abscess developed and was managed with craniotomy. CSF leak
      occurred in nine cases, intraventricular haemorrhages in two, technical failures
      in seven, subcutaneous CSF collection (managed with lumbo-peritoneal shunt) in
      one, thalamic contusion and post-operative transient akinetic mutism in one. This
      patient suddenly died 6 months later, probably as a consequence of closure of the
      stoma. Two patients developed secondary compartmentalisation of the ventricles
      after complicated endoscopic third ventriculostomy. In nine cases, these
      complications were associated. Overall, no patient died after the procedure
      (operative mortality 0), one patient died 6 months after the procedure for
      unexplained events (sudden death rate 0.4%), and three patients presented
      permanent disability as a consequence of surgical complication (permanent
      morbidity 1.3%). CONCLUSIONS: Complication rate of neuro-endoscopic procedures is
      not negligible even in experienced hands. The majority are minor complications
      which do not affect the final outcome, but sporadically major events may occur,
      leading to significant problems in surgical management and, occasionally, to
      permanent disabilities. Careful selection of patients on pre-operative imaging
      studies and intensive training of surgeons are mandatory to improve results.

PMID- 17447075
TI  - Endocrine evaluation after endoscopic third ventriculostomy (ETV) in children.
AB  - OBJECTIVE: Endoscopic third ventriculostomy (ETV) is a standard procedure for the
      treatment of obstructive hydrocephalus in children. Main part of the procedure is
      the perforation of the third ventricle floor (tuber cinereum). This structure is
      part of the hypothalamic-pituitary neuronal network of cerebral endocrine
      regulation. There are no systematic data available about the endocrine status
      after ETV in children. MATERIALS AND METHODS: We examined 20 children who had
      undergone ETV. Examination included laboratory tests (adrenocorticotropic
      hormone, prolactin, insulin-like growth factor 1 [IGF-1], IGF-binding protein 3
      [IGFBP-3], fT3, fT4, thyroid-stimulating hormone [TSH], serum osmolarity,
      electrolytes, glucose, urea, follicle-stimulating hormone [FSH] and luteinizing
      hormone [LH], and testosterone in selected patients), measurement of weight,
      height, and head circumference, and physical examination. The study was approved
      by the Ethics Committee of the Medical Faculty of Kiel University. RESULTS: In
      seven patients, prolactin was moderately elevated. One patient demonstrated a
      significantly increased prolactin (56.3 ng/ml). In all eight patients, this was
      the only laboratory value that was out of the normal range; all other parameters
      were normal. Three other patients showed one abnormal parameter (decrease in FSH
      and LH, increase in TSH, decrease in IGF-1 and IGFBP-3). In nine patients, weight
      or height was not within the 3rd to 97th centiles for age. DISCUSSION AND
      CONCLUSION: More patients than expected demonstrated endocrine laboratory
      abnormalities. However, there was no clinical relevance in any of the studied
      patients. It remains inconclusive whether ETV contributes to the abnormalities of
      prolactin levels or to other endocrine parameters in pediatric patients.
      Longitudinal studies are necessary to delineate the effect of ETV on endocrine
      regulation.

PMID- 17447076
TI  - The cistern.

PMID- 17447077
TI  - Holoprosencephaly in Mexico: first reported autopsy case by Dr. Agustin Arellano.
AB  - INTRODUCTION: Holoprosencephaly with cyclocephaly is an early disturbance of
      organogenesis and has been classified as a severe brain malformation starting in
      1755 by Eller in Germany, then in 1822 by Etienne Geoffroy de Saint-Hilaire in
      France, and finally in 1828 by Tiedemann in Germany. In 1839, Dr. Arellano
      published in Mexico a necropsy case of holoprosencephaly. This was the fourth
      publication worldwide on this kind of pathological alteration. Furthermore, in
      reference to diaphragmatic herniation, Arellano's paper is the fourth world
      report, having appeared 9 years before Bochdalek's publication. We have not found
      any other report that appeared before 1839 in the Americas on this particular
      malformation, and we consider that Arellano's paper was the first of its kind on
      the American continent. CONCLUSION: As is well known, the publications of this
      Mexican medical researcher were, for his time, at the level of those of the most
      developed countries. It is also important to know that the medical journal where
      Arellano's work was published, the "Periodico de la Academia de Medicina de
      Megico(sic)," founded and directed by Dr. Manuel Carpio in 1836, is the direct
      forerunner of the present Gaceta Medica de Mexico, the oldest currently published
      journal in the Americas.

PMID- 17447078
TI  - Malignant neoplasms of the appendix.
AB  - BACKGROUND: Appendiceal neoplasms, first described in 1882, are still rare, with
      pre-operative diagnosis invariably difficult. We present our 10-year experience
      of these lesions with a review of current epidemiology, pathology and treatment
      modalities. MATERIALS AND METHODS: A retrospective histopathological review of
      all appendicectomy specimens was completed between April 1994 and December 2003
      to identify patients diagnosed with malignant neoplasms. Patient demographics,
      operative details, histopathology and clinical outcomes were obtained from case
      notes. A literature search of the PubMed database was then performed using the
      medical search headings; appendix, tumour, neoplasm and malignancy. RESULTS:
      Twenty-two patients (eight men) were identified during the study period, with no
      age difference between gender (mean age in women 58, range 14-83 vs mean age in
      men 55, range 16-78). Eleven patients were found to have carcinoid-type tumours,
      eight patients with adenocarcinomas and three patients with lymphomas. Other
      appendiceal pathologies were identified after appendicectomies, hemicolectomy and
      oophorectomy. Mean follow-up was 41 months (range 1-125 months). Fourteen
      patients were alive at the end of follow-up. Patients with classical carcinoid
      tumours (CCT) had better outcomes than patients with the goblet cell carcinoid,
      adenocarcinoma and lymphoma. CONCLUSIONS: From our own experience and a
      subsequent review of the literature, we recommend right hemicolectomy as the
      treatment of choice for all malignant appendiceal neoplasms, except for small CCT
      less than 2 cm in diameter at the tip of the appendix, with a low proliferative
      index, without angiolymphatic or mesoappendiceal extension. Further adjuvant
      therapy should be considered after oncological assessment.

PMID- 17447079
TI  - Twenty-five years experience with laser surgery for head and neck tumors : report
      of an international symposium, Gottingen, Germany, 2005.
AB  - During the last 25 years, the treatment of tumors arising in the upper
      aerodigestive tract has changed fundamentally. Whereas surgery in the 1970s aimed
      at radical block resection and defect repair from outside, the establishment of
      transoral laser microsurgery marked a new era of organ- and function-preserving
      therapy. An international symposium, held on 10 and 11 June 2005 in Gottingen,
      was dedicated to a critical review and assessment of the current role of laser
      surgery for the treatment of head and neck cancer. Experts from five continents
      presented their experiences and scientific results and had an intensive exchange
      with participants from different countries. The topics of the symposium were
      focused on the surgical principles of laser resection, the oncological and
      functional results in comparison with traditional therapy, the difficulties and
      limits of laser surgery in distinct anatomical regions and on the role of
      radiotherapy. This report summarizes the most important results and statements
      and gives an overview of actual developments. The names and addresses of the
      participants mentioned in this report are appended below.

PMID- 17447080
TI  - Structural differences in centromeric heterochromatin are spatially reconciled on
      fertilisation in the mouse zygote.
AB  - In mammals, paternal and maternal pronuclei undergo profound chromatin
      reorganisation upon fertilisation. How these events are orchestrated within
      centromeric regions to ensure proper chromosome segregation in the following
      cellular divisions is unknown. In this study, we followed the dynamic unfolding
      of the centromeric regions, i.e. the centric and pericentric satellite repeats,
      by DNA fluorescent in situ hybridization (FISH) during the first cell cycle up to
      the two-cell stage. The distinct chromatin from female and male gametes both
      undergo rapid remodelling and reach a zygotic organisation in which the
      satellites occupy restricted spatial domains surrounding the nucleolar precursor
      body. A transition from this zygotic to a somatic cell-like organisation takes
      place during the two-cell stage. Using 3D immuno-FISH, we find that, whereas
      maternal pericentric regions are marked with H3K9me3, H4K20me3 and HP1beta,
      paternal ones only showed HP1beta marking. Thus, despite different chromatin
      features, male and female pronuclei organise their centromeric regions in the
      same way within the nuclei to align chromosomes on the metaphase plate and
      segregate them appropriately. Our findings highlight the importance of ensuring a
      proper centromere function while preserving the distinction of parental genome
      origin during the return to totipotency in the zygote.

PMID- 17447081
TI  - PIP(2)-dependent inhibition of M-type (Kv7.2/7.3) potassium channels: direct on
      line assessment of PIP(2) depletion by Gq-coupled receptors in single living
      neurons.
AB  - The open state of M(Kv7.2/7.3) potassium channels is maintained by membrane
      phosphatidylinositol-4,5-bisphosphate (PI(4,5)P(2)). They can be closed on
      stimulating receptors that induce PI(4,5)P(2) hydrolysis. In sympathetic neurons,
      closure induced by stimulating M1-muscarinic acetylcholine receptors (mAChRs) has
      been attributed to depletion of PI(4,5)P(2), whereas closure by bradykinin B(2)
      receptors (B2-BKRs) appears to result from formation of IP(3) and release of
      Ca(2+), implying that BKR stimulation does not deplete PI(4,5)P(2). We have used
      a fluorescently tagged PI(4,5)P(2)-binding construct, the C-domain of the protein
      tubby, mutated to increase sensitivity to PI(4,5)P(2) changes (tubby-R332H-cYFP),
      to provide an on-line read-out of PI(4,5)P(2) changes in single living
      sympathetic neurons after receptor stimulation. We find that the mAChR agonist,
      oxotremorine-M (oxo-M), produces a near-complete translocation of tubby-R332H
      cYFP into the cytoplasm, whereas bradykinin (BK) produced about one third as much
      translocation. However, translocation by BK was increased to equal that produced
      by oxo-M when synthesis of PI(4,5)P(2) was inhibited by wortmannin. Further,
      wortmannin 'rescued' M-current inhibition by BK after Ca(2+)-dependent inhibition
      was reduced by thapsigargin. These results provide the first direct support for
      the view that BK accelerates PI(4,5)P(2) synthesis in these neurons, and show
      that the mechanism of BKR-induced inhibition can be switched from Ca(2+)
      dependent to PI(4,5)P(2) dependent when PI(4,5)P(2) synthesis is inhibited.

PMID- 17447082
TI  - Aquaporin expression in response to different water stress intensities and
      recovery in Richter-110 (Vitis sp.): relationship with ecophysiological status.
AB  - Aquaporins seem essential for the regulation of plant water status and expenses.
      Richter-110 is a Vitis hybrid (Vitis berlandieri x rupestris) reputed to be
      strongly drought-tolerant. Three irrigation treatments were established in
      Richter-110 plants growing outdoors defined by the resulting maximum stomatal
      conductance (g (s)), and ensuring water stress situations not severe enough as to
      stop photosynthesis and growth: well-watered plants (g (s) about 250 mmol H(2)O
      m(-2) s(-1)), moderate water stress (g (s) about 150 mmol H(2)O m(-2) s(-1)) and
      severe water stress (g (s) about 50 mmol H(2)O m(-2) s(-1)). Plants under water
      stress were kept at constant water availability for 7 days to check for possible
      acclimation. Finally, plants were re-watered, and allowed to recover, for 3 days.
      Stomatal conductance, leaf water potential, xylem abscisic acid (ABA) content and
      root and stem hydraulic conductivity were determined. The relative amounts of
      expression of mRNA encoding seven putative aquaporins were determined in roots
      and leaves by RT-PCR. The decrease in stomatal conductance with moderate and
      severe water stress was associated with increasing ABA contents, but not with the
      leaf water potential and hydraulic conductivities, which remained unchanged
      during the entire experiment. Aquaporin gene expression varied depending on which
      aquaporin, water stress level and the plant organ. We suggest that aquaporin
      expression was responsive to water stress as part of the homeostasis, which
      resulted in constant leaf water potential and hydraulic conductivity.

PMID- 17447083
TI  - Solving the credit assignment problem: explicit and implicit learning of action
      sequences with probabilistic outcomes.
AB  - In most problem-solving activities, feedback is received at the end of an action
      sequence. This creates a credit-assignment problem where the learner must
      associate the feedback with earlier actions, and the interdependencies of actions
      require the learner to remember past choices of actions. In two studies, we
      investigated the nature of explicit and implicit learning processes in the credit
      assignment problem using a probabilistic sequential choice task with and without
      a secondary memory task. We found that when explicit learning was dominant,
      learning was faster to select the better option in their first choices than in
      the last choices. When implicit reinforcement learning was dominant, learning was
      faster to select the better option in their last choices than in their first
      choices. Consistent with the probability-learning and sequence-learning
      literature, the results show that credit assignment involves two processes: an
      explicit memory encoding process that requires memory rehearsal and an implicit
      reinforcement-learning process that propagates credits backwards to previous
      choices.

PMID- 17447084
TI  - Cerebral sinovenous thrombosis in a child with steroid sensitive nephrotic
      syndrome.

PMID- 17447085
TI  - Root foraging traits and competitive ability in heterogeneous soils.
AB  - The responses of plant roots to nutrient patches in soil may be an important
      component of competitive ability. In particular, the scale, precision, and rate
      of foraging for patchy soil resources may influence competitive ability in
      heterogeneous soils. In a target-neighbor experiment in the field, per-individual
      and per-gram competitive effects were measured for six old-field species with
      known root foraging scale, precision, and rate. The presence and number of
      nutrient patches were also manipulated in a full factorial design. Number and
      presence of patches did not influence the outcome of competition. Competitive
      ability was not related to total plant size, growth rate, or root:shoot
      allocation, or to root foraging precision. Per-individual competitive effects
      were marginally correlated with root foraging scale (biomass of roots) and root
      foraging rate (time required to reach a patch). Therefore, competitive ability
      was more closely related to ability to quickly fill a soil volume with roots than
      to ability to preempt resource-rich patches.

PMID- 17447086
TI  - Dying at home or in an institution: perspectives of Dutch physicians and bereaved
      relatives.
AB  - INTRODUCTION: Previous studies have shown that most people prefer to die at their
      own home. We investigated whether physicians or bereaved relatives in retrospect
      differently appreciate the dying of patients in an institution or at home.
      MATERIALS AND METHODS: Of 128 patients with incurable cancer who were followed in
      the last phase of their lives, 103 passed away during follow-up. After death,
      physicians filled out a written questionnaire for 102 of these patients, and 63
      bereaved relatives were personally interviewed. RESULTS: Of 103 patients, 49 died
      in an institution (mostly a hospital), and 54 died at home (or in two cases in a
      home-like situation). Patients who had been living with a partner relatively
      often died at home. Bereaved relatives knew of the patient's wish to die at home
      in 25 out of 63 cases; 20 of these patients actually died at home. Thirty-one
      patients had no known preference concerning their place of dying. Most symptoms
      and the care provided to address them were equally prevalent in patients dying in
      an institution and patients dying at home. Bereaved relatives were in general
      quite satisfied about the provision of medical and nursing care in both settings.
      CONCLUSION: We conclude that most patients' preferences concerning the place of
      dying can be met. In about half of all cases, patients do not seem to have a
      clear preference concerning their place of dying, which is apparently not a major
      concern for many people. We found no indication that dying in an institution or
      at home involves major differences in the process and quality of dying.

PMID- 17447087
TI  - The effect of pre-vertebroplasty tumor ablation using laser-induced thermotherapy
      on biomechanical stability and cement fill in the metastatic spine.
AB  - A biomechanical study comparing simulated lytic vertebral metastases treated with
      laser-induced thermotherapy (LITT) and vertebroplasty versus vertebroplasty
      alone. To investigate the effect of tumor ablation using LITT prior to
      vertebroplasty on biomechanical stability and cement fill patterns in a
      standardized model of spinal metastatic disease. Vertebroplasty in the metastatic
      spine is aimed at reducing pain, but is associated with risk of cement
      extravasation in up to 10%. Six pairs of fresh-frozen cadaveric thoracolumbar
      spinal motion segments were tested in axial compression intact, with simulated
      metastases and following percutaneous vertebroplasty with or without LITT. Canal
      narrowing under load, pattern of cement fill, load to failure, and LITT
      temperature and pressure generation were collected. In all LITT specimens, cement
      filled the defect without extravasation. The canal extravasation rate was 33% in
      specimens treated without LITT. LITT and vertebroplasty yielded a trend toward
      improved posterior wall stability (P = 0.095) as compared to vertebroplasty
      alone. Moderate rises in temperature and minimal pressure generation was seen
      during LITT. In this model, elimination of tumor by LITT, facilitates cement
      fill, enhances biomechanical stability and reduces the risk of cement
      extravasation.

PMID- 17447088
TI  - Porous silk scaffolds can be used for tissue engineering annulus fibrosus.
AB  - There is no optimal treatment for symptomatic degenerative disc disease which
      affects millions of people worldwide. One novel approach would be to form a patch
      or tissue replacement to repair the annulus fibrosus (AF) through which the NP
      herniates. As the optimal scaffold for this has not been defined the purpose of
      this study was to determine if porous silk scaffolds would support AF cell
      attachment and extracellular matrix accumulation and whether chemically
      decorating the scaffold with RGD peptide, which has been shown to enhance
      attachment for other cell types, would further improve AF cell attachment and
      tissue formation. Annulus fibrosus cells were isolated from bovine caudal discs
      and seeded into porous silk scaffolds. The percent cell attachment was quantified
      and the cell morphology and distribution within the scaffold was evaluated using
      scanning electron microscopy. The cell-seeded scaffolds were grown for up to 8
      weeks and evaluated for gene expression, histological appearance and matrix
      accumulation. AF cells attach to porous silk scaffolds, proliferate and
      synthesize and accumulate extracellular matrix as demonstrated biochemically and
      histologically. Coupling the silk scaffold with RGD-peptides did not enhance cell
      attachment nor tissue formation but did affect cell morphology. As well, the
      cells had higher levels of type II collagen and aggrecan gene expression when
      compared to cells grown on the non-modified scaffold, a feature more in keeping
      with cells of the inner annulus. Porous silk is an appropriate scaffold on which
      to grow AF cells. Coupling RGD peptide to the scaffold appears to influence AF
      cell phenotype suggesting that it may be possible to select an appropriate
      scaffold that favours inner annulus versus outer annulus differentiation which
      will be important for tissue engineering an intervertebral disc.

PMID- 17447089
TI  - Theoretical study of geometrical and nonlinear optical properties of pyridinum N
      phenolate betaine dyes.
AB  - This paper presents an ab initio quantum chemical investigation of the
      geometrical structures and the non-linear optical properties (NLO) of three
      structural isomers of pyridinium N-phenolate betaine dye. The ground state
      geometrical parameters and the first-order hyperpolarizabilities were calculated
      using the Hartree-Fock (HF) as well as the second-order perturbation Moller
      Pleset (MP2) method with the 6-31G, 6-31G(d), 6-31G(d,p), 6-31+G(d), 6
      31++G(d,p), 6-311+G(d), aug-cc-PVDZ and the recently developed Z3PolX basis sets.
      Moreover, the first-order hyperpolarizability was calculated at the coupled
      cluster singles and doubles (CCSD/6-31+G(d)) level of theory. The analysis of the
      results of calculations for the investigated isomers indicates that there are
      important differences in their NLO activities. Additionally, it was shown that
      Z3PolX basis set works reasonable well for betaine dyes.

PMID- 17447090
TI  - Differentiation of Candida albicans from non-albicans yeast directly from blood
      cultures by Gram stain morphology.
AB  - Clusters of pseudohyphae are commonly seen on Gram stain of blood cultures from
      patients with Candida albicans fungemia. Whether this morphologic feature is
      useful for differentiating C. albicans from other yeasts has not previously been
      systematically evaluated. Yeast morphology on Gram stain of blood cultures from
      consecutive patients with fungemia detected by the Bactec automated blood culture
      system was prospectively assessed and correlated with the final culture-based
      yeast identification. The distribution of yeast in 60 consecutive patients with
      fungemia included Candida spp. (C. albicans 43%, Candida glabrata 28%, Candida
      parapsilosis 8%, Candida krusei 7%, Candida tropicalis 5%, Candida dubliniensis
      2%, and Candida lusitaniae 2%), Rhodotorula mucilaginosa 2%, and Cryptococcus
      neoformans 3%. Upon analysis of the first positive blood culture bottle per
      patient, the presence of clustered pseudohyphae on Gram stain had a sensitivity,
      specificity, positive predictive value, and negative predictive value of 85, 97,
      96, and 89%, respectively, for C. albicans. The sensitivity and specificity of
      aerobic vs Myco/F blood culture bottles were 96 and 95% vs 25 and 100%, p <
      0.001, respectively. Inter-rater agreement for ten separate observations among
      five reviewers was 100%. The presence of pseudohyphae clusters by Gram stain of
      blood cultures is useful in distinguishing C. albicans from non-albicans yeast.
      Additional studies are necessary to determine the clinical impact of these
      findings and their validity with other blood culture systems.

PMID- 17447093
TI  - Comment on: Should we really worry about "launch delays" of new drugs in OECD
      countries? by L. Garatinni and S. Ghislandi.

PMID- 17447091
TI  - Detection by PCR of eight groups of enteric pathogens in 4,627 faecal samples: re
      examination of the English case-control Infectious Intestinal Disease Study (1993
      1996).
AB  - The English case-control Infectious Intestinal Disease Study (1993-1996) failed
      to detect an enteric pathogen or toxin in 49% of cases of gastroenteritis. In the
      present study, polymerase chain reaction (PCR) assays were applied to DNA and
      cDNA generated from 4,627 faecal samples from cases and controls archived during
      the original study for the detection of norovirus, rotavirus, sapovirus,
      Campylobacter spp., Salmonella spp., enteroaggregative Escherichia coli,
      Cryptosporidium spp., and Giardia spp. The percentage of archived samples from
      cases and from controls in which at least one agent (or toxin) was detected
      increased from 53% in the original study to 75% and from 19 to 42%, respectively,
      after the application of PCR assays. Among cases, the following percentages of
      enteric pathogens were detected: norovirus 36%, rotavirus A 31%, sapovirus 4%,
      Salmonella spp. 6%, Campylobacter jejuni 13%, Campylobacter coli 2%, other
      Campylobacter spp. 8%, enteroaggregative E. coli 6%, Giardia spp. 2%, and
      Cryptosporidium spp. 2%. The present study provides additional insight into the
      aetiology of infectious intestinal disease in England and highlights the
      occurrence of viral infections in cases as well as in asymptomatic individuals.
      Other notable findings include the frequent presence of Campylobacter spp. other
      than C. jejuni or C. coli, the high frequency of multiple agents in 41% of cases
      and in 13% of controls, and the variation in the aetiology and rate of infection
      found for different age groups. The results demonstrate the greater sensitivity
      of PCR-based methods compared to current conventional methods.

PMID- 17447094
TI  - The search for good compliance: economic aspects of a conveyed combination
      pharmaco-therapy, exemplified by an osteoporosis therapy.
AB  - The discussion of adequate compliance in health care often refers to a lack of
      information between patients and physicians. In our setting, we show that
      contract arrangements as well as the distribution of information are important
      for an adequate alignment of the interest of patients and physicians. The
      analysis emphasises the benefit of organised pharmaco-therapy enhancing the
      concomitant compliance. Therefore, the results can work as a proxy for the need
      of good economic-based approaches discussing compliance in chronic diseases.

PMID- 17447095
TI  - Willingness to pay for a reduction in mortality risk after a myocardial
      infarction: an application of the contingent valuation method to the case of
      eplerenone.
AB  - In order to allocate health care resources more efficiently, it is necessary to
      relate health improvements provided by new medicines to their cost. It is
      necessary to ascertain when the additional cost of introducing a new health
      technology is justified by the additional health gain produced. Eplerenone is a
      new medicine that reduces the risk of death after myocardial infarction (MI) but
      produces additional cost to the health system. The contingent valuation approach
      can be used to measure the monetary value of this risk reduction and to estimate
      society's willingness to pay (WTP) for a new medicine that reduces the risk of
      death after MI by 2% points. We used a contingent valuation approach to evaluate
      WTP amongst members of the general population. We used the ex-ante and the ex
      post approach. In the ex-ante approach, subjects are asked if they would accept
      an increase in their taxes in order to have access to eplerenone should they need
      it in the future. In the ex-post approach, subjects are asked if they would pay a
      certain amount of money as co-payment per month during 5 years if they suffered
      an MI. We used the dichotomous choice method, using five bids in each approach.
      The WTP was estimated using both single-bound and double-bound dichotomous choice
      (SBDC, DBDC). Extensive piloting (n = 187) preceded the final survey (n = 350).
      The WTP in the ex-ante case was euro 58 per year under both SBDC and DBDC. In the
      ex-post case, monthly WTP was euro 141 for the SBDC and euro 85 for the DBDC.
      Subjects with higher income and subjects with a higher perception of risk showed
      a higher WTP (P 0.05). Society is willing to pay an additional amount of money in
      order to give eplerenone to present and future patients. We estimate that euro 85
      per month is a conservative estimate of the monetary value of a 2% risk reduction
      in mortality after MI and to spend this additional amount of money in Eplerenone
      can be considered an efficient policy.

PMID- 17447096
TI  - Investigating the location of propyl gallate at surfaces and its chemical
      microenvironment by (1)H NMR.
AB  - The location and the resulting chemical microenvironment of the antioxidant
      propyl gallate (PG) was studied in micellar solutions using the cationic
      emulsifier cetyl trimethyl ammonium bromide (CTAB), the anionic emulsifier sodium
      dodecyl sulphate (SDS) and the non-ionic emulsifier Brij 58 (polyoxyethylene-20
      cetyl ester). T (1) relaxation time of the aromatic protons of PG was
      investigated in micellar solutions and compared with that in aqueous solution in
      the absence of emulsifier. The relaxation time of the PG portion that is
      solubilized in the micelle (T (1,eff)) was calculated from the partition behavior
      of PG in micellar solution. From the 1D-(1)H spectrum, the alteration in the
      electron density of the aromatic protons and the alteration in the peak shape of
      the emulsifier headgroup and alkyl chain proton signals were indicative of the
      location of propyl gallate in the different micelles. Nuclear Overhauser effects
      (NOE) made it possible to deduce the exact location of PG by calculation of the
      relative NOEs. Marked differences were found for the location of PG in CTAB, SDS
      and Brij 58 micelles. PG was found to be located in the palisade layer of CTAB
      micelles, in the region of the polyoxyethylene chain of Brij micelles and in the
      Stern layer of SDS micelles. For careful study of the location of antioxidants
      and therefore to be able to characterize the chemical microenvironment of the
      antioxidants is crucial for understanding differences in antioxidant activities
      as a function of lipid surfaces. The application of spectroscopic methods may
      help to optimize the antioxidant activity to inhibit lipid oxidation at surfaces
      that are formed in a wide range of foods (emulsions), cosmetics, pharmaceuticals
      (emulsions and carrier systems) and of biological membranes (LDL-particles).

PMID- 17447097
TI  - Obese African-American women's perspectives on weight loss and bariatric surgery.
AB  - BACKGROUND: African-American (AA) women have higher rates of obesity and obesity
      related diseases but are less likely than other women to undergo bariatric
      surgery or have success with conventional weight loss methods. OBJECTIVE: To
      explore obese AA women's perceptions regarding barriers to weight loss and
      bariatric surgery. DESIGN: Focus groups to stimulate interactive dialogue about
      beliefs and attitudes concerning weight management. PARTICIPANTS AND APPROACH: We
      partnered with a community organization to recruit women who were AA, were > or =
      18 years old, and had a body mass index (BMI) of > or = 30 kg/m2. We audiotaped
      the 90-minute focus groups and used content analysis for generating and coding
      recurring themes. RESULTS: In our sample of 41 participants, the mean age was
      48.8 years and mean BMI was 36.3. Most participants were unmarried, had some
      postsecondary education, and reported good or fair health. About 85% knew someone
      who had undergone bariatric surgery. Qualitative analysis of 6 focus group
      sessions revealed that the most common barriers to weight loss were lack of time
      and access to resources; issues regarding self-control and extrinsic control; and
      identification with a larger body size. Common barriers to bariatric surgery were
      fears and concerns about treatment effects and perceptions that surgery was too
      extreme or was a method of last resort. CONCLUSIONS: Only through the elimination
      of barriers can AA women receive the care needed to eliminate excess weight and
      prevent obesity-related morbidity and mortality.

PMID- 17447098
TI  - An unusual case of cardiac amyloidosis.
AB  - Cardiac amyloidosis can result from any of the systemic amyloidoses. The disease
      is often characterized by a restrictive cardiomyopathy although the particular
      signs and symptoms depend in part on the underlying cause. In addition to
      managing the symptoms of heart failure, treatment options vary depending on the
      etiology of amyloid deposition. It is therefore critical to identify the cause of
      cardiac amyloidosis before initiating definitive therapy. We present a patient
      with presumed immunoglobulin (AL) amyloidosis who had a circulating lambda
      monoclonal protein, but a bone marrow biopsy with kappa predominant plasma cells.
      This unusual finding called into question the diagnosis of AL amyloidosis and
      highlights the importance and difficulty of determining the cause of cardiac
      amyloid deposition before initiating treatment. We review the different forms of
      cardiac amyloidosis and propose a diagnostic algorithm to help identify the
      etiology of cardiac amyloid deposition before beginning therapy.

PMID- 17447099
TI  - The influence of default options on the expression of end-of-life treatment
      preferences in advance directives.
AB  - BACKGROUND: Advance directives promise to preserve patient autonomy, but research
      indicates that end-of-life preferences can be influenced by the way in which
      questions are posed. OBJECTIVE: To determine whether preferences expressed by
      geriatric patients on advance directives are influenced by the default response
      inherent in the question. DESIGN: Mailed survey containing 1 of 3 versions of an
      advance directive. SETTING: General internal medicine outpatient medical
      practice. PARTICIPANTS: Outpatients aged 65 or older (n = 106, response rate =
      27%). INTERVENTIONS: In the "withhold" version of the survey, participants
      indicated situations where they would want treatments withheld (i.e., the default
      preference was in favor of treatment). In the "provide" version, participants
      indicated situations where they would want treatment provided (i.e., the default
      preference was against treatment). In the forced-choice control version,
      participants made an explicit decision to withhold or provide treatment for each
      situation. MAIN OUTCOME MEASURE: Participants' treatment preferences. RESULTS:
      Preferences differed by condition, F(2, 103) = 3.61, MSE = 0.09, eta2 = .07, p =
      .03. Participants tended to express the default preference, and thus, were more
      likely to favor treatment in the "withhold" condition than in the "provide"
      condition. Preferences in the forced-choice control condition were intermediate.
      CONCLUSIONS: The default inherent in a question can impact preferences for
      medical treatment. This default effect limits the utility of advance directives.

PMID- 17447100
TI  - Implementing routine cognitive screening of older adults in primary care: process
      and impact on physician behavior.
AB  - BACKGROUND: Early detection of cognitive impairment is a goal of high-quality
      geriatric medical care, but new approaches are needed to reduce rates of missed
      cases. OBJECTIVE: To evaluate whether adding routine cognitive screening to
      primary care visits for older adults increases rates of dementia diagnosis,
      specialist referral, or prescribing of antidementia medications. SETTING: Four
      primary care clinics in a university-affiliated primary care network. DESIGN: A
      quality improvement screening project and quasiexperimental comparison of 2
      intervention clinics and 2 control clinics. The Mini-Cog was administered by
      medical assistants to intervention clinic patients aged 65+ years. Rates of
      dementia diagnoses, referrals, and medication prescribing were tracked over time
      using computerized administrative data. RESULTS: Twenty-six medical assistants
      successfully screened 70% (n = 524) of all eligible patients who made at least 1
      clinic visit during the intervention period; 18% screened positive. There were no
      complaints about workflow interruption. Relative to baseline rates and control
      clinics, Mini-Cog screening was associated with increased dementia diagnoses,
      specialist referrals, and prescribing of cognitive enhancing medications.
      Patients without previous dementia indicators who had a positive Mini-Cog were
      more likely than all other patients to receive a new dementia diagnosis,
      specialty referral, or cognitive enhancing medication. However, relevant
      physician action occurred in only 17% of screen-positive patients. Responses were
      most related to the lowest Mini-Cog score level (0/5) and advanced age.
      CONCLUSION: Mini-Cog screening by office staff is feasible in primary care
      practice and has measurable effects on physician behavior. However, new physician
      action relevant to dementia was likely to occur only when impairment was severe,
      and additional efforts are needed to help primary care physicians follow up
      appropriately on information suggesting cognitive impairment in older patients.

PMID- 17447101
TI  - Abstracts of the 48th Spring Meeting of the German Society for Experimental and
      Clinical Pharmacology and Toxicology, March 13-15, 2007, Mainz, Germany.

PMID- 17447102
TI  - The role of histone ubiquitylation and deubiquitylation in gene expression as
      determined by the analysis of an HTB1(K123R) Saccharomyces cerevisiae strain.
AB  - In Saccharomyces cerevisiae histone H2B is ubiquitylated at lysine 123 in a
      process requiring the E2-ubiquitin conjugase, Rad6. We have analyzed gene
      expression in a strain containing a variant of histone H2B with lysine 123
      converted to arginine to address the mechanisms by which ubiquitylation and
      deubiquitylation of histone H2B affect gene expression. The SAGA complex
      component, Ubp8, is one of two proteases that remove the ubiquitin moiety at
      lysine 123. We show that changes in gene expression observed upon deletion of
      ubp8 are suppressed by htb1 ( K123R ), which provides genetic evidence that Ubp8
      alters gene expression through deubiquitylation of histone H2B. Microarray
      analyses of the htb1 ( K123R ) strain show that loss of histone ubiquitylation
      results in a twofold or greater change in expression of approximately 1.5% of the
      protein coding genes with approximately 75% of these increasing. For genes in
      which ubiquitylation represses expression, ubiquitylation principally acts
      through its effects on histone methylation. In contrast, decreased expression of
      the CWP1 gene was not paralleled by deletions of methyltransferase components and
      is thus likely independent of methylation. Finally, by comparing gene expression
      changes in the htb1 ( K123R ) strain with those in a strain deleted for rad6, we
      conclude that lysine 123 affects transcription primarily because of it being a
      site of ubiquitylation.

PMID- 17447103
TI  - Abnormal surface markers expression on bone marrow CD34+ cells and correlation
      with disease activity in patients with systemic lupus erythematosus.
AB  - Defects of hematopoietic stem cells (HSCs) have been suggested to contribute to
      the development of systemic lupus erythematosus (SLE). The aim of this study was
      to investigate the phenotypic characteristics of bone marrow (BM) CD34(+) cells
      in patients with SLE and its relationship with SLE disease activity. Ten SLE
      patients and 10 healthy subjects were recruited and their BM CD34(+) cells were
      analyzed by flow cytometric analysis with CD45/SSC gating for the expression of
      CD90, CD95, CD117, CD123, CD164, CD166, FAS-L, and HLA-DR. The percentage of BM
      CD34(+) cells was significantly decreased in active SLE patients (1.48 +/- 0.41%,
      n = 7) compared to the healthy controls (2.31 +/- 0.75%, n = 10, p < 0.01), but
      no significant difference was found between the inactive patients (2.04 +/-
      0.44%, n = 3) and the controls. The expression of CD95, CD123, and CD166 on BM
      CD34(+) cells were significantly increased in SLE patients (48.31 +/- 10.59%,
      44.9 +/- 21.5%, 30.9 +/- 19.54%, respectively, n = 10) when compared with the
      control subjects (24.33 +/- 11.1%, 19.5 +/- 4.4%, 10.7 +/- 5.5%, respectively, n
      = 10, p < 0.05). The increased CD123 expression was negatively correlated with
      the number of peripheral white blood cells (r = -0.700, p < 0.05, n = 10). The
      percentage of CD166 expression was found significantly correlated with the index
      of SLE disease activity (r = 0.472, p < 0.05, n = 10) and 24 h proteinuria (r =
      0.558, p < 0.05, n = 10), but negatively correlated with serum C3 level (r = 
      0.712, p < 0.01, n = 10). Our study found that the surface marker expression of
      CD95, CD123, and CD166 on BM CD34(+) cells were significantly increased in
      patients. This supports the hypothesis that there are abnormalities of the HSC in
      SLE. Since CD166 and CD123 correlated with the overall lupus activity, their role
      as a biomarker of inflammatory disease activity also requires further study.

PMID- 17447104
TI  - Patients' perspective: lupus in patients' drawings. Assessing drawing as a
      diagnostic and therapeutic method.
AB  - This is the first report from a qualitative research on lupus patients'
      perspective expressed in the disease drawings. The aim of the study was to
      examine the variety of ways of illness perception and experiences among systemic
      lupus erythematosus (SLE) patients. The goal was also to assess the utility of
      drawing as an unconventional research method as well as a therapeutic means.
      Participants were 38 women with SLE. Patients attended 'My life' courses
      addressed to the lupus patients held in 2000-2002. During the psychological group
      sessions, subjects were asked to draw their disease and then to comment on their
      pictures. There were no time limits. The participants were ensured that their
      drawing abilities had no meaning. Despite initial hesitation, all of the patients
      drew their pictures. This report presents three lupus patients' drawings.
      Analysis of disease pictures reveals that they are the priceless source of
      information on patients' perspective and make many dimensions of living with the
      disease uncovered, especially psychological. This unconventional, nonverbal
      method allows patient to know and realize one's emotions and feelings. From
      health professionals' point of view, the advantage of drawing as a research
      method is the possibility of gaining much information that cannot be gained from
      interview or traditional tests alone. Drawing is a 'good beginning' to talk, it
      makes the patients open up to share their emotions, views, and experiences. Thus,
      it can be the useful therapeutic method. It can also prevent health professionals
      from schematization in approach to the patients with the same diagnosis.

PMID- 17447105
TI  - An audit of the impact of implementation of a stroke care pathway in an acute
      teaching hospital.
AB  - BACKGROUND: In 2002, a survey of stroke management was conducted in our
      institution benchmarked against the UK National Stroke Audit 2002. The conclusion
      was that management of stroke patients lacked organised and specialised care. The
      introduction of a stroke care pathway was recommended. AIMS: This audit assessed
      the clinical impact of implementation of a stroke care pathway by the general
      medical teams in an acute teaching hospital. METHODS: A random sample of 48/131
      patients were surveyed in 2002 compared to 55 consecutive patients admitted with
      stroke in 2005. RESULTS: Despite introduction of a stroke care pathway, marked
      deficits persisted in acute management including delays in brain imaging and
      aspirin administration, assessment of acute parameters and interdisciplinary
      care. CONCLUSIONS: Optimal care of stroke patients cannot be achieved by
      introducing a stroke care pathway alone. We recommend the urgent establishment of
      a stroke unit with a specialist consultant-led multidisciplinary stroke team.

PMID- 17447106
TI  - Ectopic splenic tissue presenting as a scrotal mass.

PMID- 17447107
TI  - Laparoscopic prophylactic oophorectomy plus N3 lymphadenectomy for advanced
      rectosigmoid cancer.
AB  - BACKGROUND: The primary aim of the present retrospective study was to evaluate
      the feasibility and efficacy of laparoscopic prophylactic oophorectomy plus N3
      lymph node dissection for patients with rectosigmoid cancer. The secondary aim
      was to explore the clinicopathologic features of ovarian micrometastasis from
      rectosigmoid cancer. METHODS: We performed 244 laparoscopic resections of
      rectosigmoid cancer in women during a 6-year period. In them, 34 patients (13.9%)
      were subjected to prophylactic oophorectomy plus N3 lymphadenectomy in addition
      to the standard anterior or low anterior resection of rectosigmoid cancer,
      because the patients presented with ovarian cystic lesions, tethering of the
      ovary to the primary rectosigmoid tumor, and/or pelvic ascites accumulation,
      which were postulated as the indicative findings for the synchronous ovarian
      micrometastasis. The surgical procedures are detailed in the attached video. The
      surgical outcomes were compared between patients with (n = 34) and without (n =
      210) these two additional procedures. In analyzing the clinicopathologic features
      of ovarian micrometastasis, we included both cases of laparoscopic (n = 34) and
      traditional open surgery (n = 30), whose prophylactic oophorectomy was performed
      by the same surgical indications. RESULTS: Although the operation time was
      significantly longer (264.2 +/- 24.5 vs. 192.5 +/- 24.2 minutes, P < .0001) in
      patients with prophylactic oophorectomy and N3 lymphadenectomy, there was no
      significant difference between patients with and without the two additional
      procedures in blood loss, wound length, postoperative complications, diverting
      ileostomy, and mortality. Although flatus passage, hospitalization, postoperative
      pain, and return to partial activity were statistically different between the
      study groups, they were deemed clinically unimportant because the difference of
      mean was very small. Foley removal was delayed in patients with N3
      lymphadenectomy by 2 days. With respect to surgical efficacy, we found that
      patients undergoing the two additional procedures could collect significantly
      more lymph nodes (22.0 +/- 4.0 vs. 14.4 +/- 2.4, P < .0001) for pathologic
      staging and facilitated upstaging of nodal status in three patients (8.8%).
      Patients undergoing prophylactic oophorectomy plus N3 lymphadenectomy could
      achieve good oncologic outcome, with the estimated 5-year survival rate of 62.5%
      and 69.2% in patients with and without ovarian micrometastasis, respectively.
      Clinicopathologically, patients with ovarian micrometastasis (n = 15) tended to
      have vascular invasion of tumor cells, as compared with those without (n = 49).
      However, ovarian micrometastasis was not related to menstrual status of patients,
      tumor location, tumor size, morphology, differentiation, mucin production, T
      stage, nodal invasion, and level of carcinoembryonic antigen. CONCLUSIONS:
      Laparoscopic surgical techniques could be safely applied to perform prophylactic
      oophorectomy plus N3 lymphadenectomy with acceptable efficacy in a highly
      selected subset of patients with rectosigmoid cancer.

PMID- 17447108
TI  - Neurodegenerative disease.

PMID- 17447109
TI  - Characterization of complete genome sequence of the spring viremia of carp virus
      isolated from common carp (Cyprinus carpio) in China.
AB  - The complete genome of spring viraemia of carp virus (SVCV) strain A-1 isolated
      from cultured common carp (Cyprinus carpio) in China was sequenced and
      characterized. Reverse transcription-polymerase chain reaction (RT-PCR) derived
      clones were constructed and the DNA was sequenced. It showed that the entire
      genome of SVCV A-1 consists of 11,100 nucleotide base pairs, the predicted size
      of the viral RNA of rhabdoviruses. However, the additional insertions in bp 4633
      4676 and bp 4684-4724 of SVCV A-1 were different from the other two published
      SVCV complete genomes. Five open reading frames (ORFs) of SVCV A-1 were
      identified and further confirmed by RT-PCR and DNA sequencing of their respective
      RT-PCR products. The 5 structural proteins encoded by the viral RNA were ordered
      3'-N-P-M-G-L-5'. This is the first report of a complete genome sequence of SVCV
      isolated from cultured carp in China. Phylogenetic analysis indicates that SVCV A
      1 is closely related to the members of the genus Vesiculovirus, family
      Rhabdoviridae.

PMID- 17447110
TI  - Identification and characterization of the NTPase activity of classical swine
      fever virus (CSFV) nonstructural protein 3 (NS3) expressed in bacteria.
AB  - The nonstructural protein 3 (NS3) of members of the family Flaviviridae possesses
      multiple enzyme activities that are likely to be essential for viral replication.
      Here, we cloned and expressed full-length CSFV NS3 protein (NS3FL) and its N
      terminal truncated version (ntNS3) in E. coli. NTPase activities of the purified
      NS3FL and ntNS3 proteins and their reaction conditions were investigated. The
      results showed that CSFV NS3FL and ntNS3 proteins contained a specific
      polynucleotide-stimulated NTPase acitivity. Characterization of ntNS3 NTPase
      activity showed that optimal reaction conditions with respect to pH, MgCl2 and
      monovalent cations were similar to those of bovine viral diarrhea virus (BVDV)
      and hepatitis C virus (HCV). Site-directed mutagenesis analysis demonstrated that
      the GxGK(232)T to GxGAT mutation in the conserved motif I abolished the NTPase
      activity of ntNS3, whereas substitution of TATPA(354) for TATPV in the motif III
      had no effect on the enzyme activity. Moreover, the kinetic properties (K(m) and
      k(cat)) of CSFV NS3 were more similar to those of BVDV. Our results provide
      insight into the structure-function relationship of CSFV NS3 and facilitate our
      understanding of its role in the replication cycle of CSFV.

PMID- 17447111
TI  - Serum 25-OHD insufficiency as a risk factor for hip fracture.
AB  - The aging population and an increasing number of hip fractures worldwide have
      made prevention of hip fractures a matter of importance. The prevalence of
      hypovitaminosis D in patients with acute hip fracture has been reported widely in
      recent years, and the vitamin D nutritional status in such reports is usually
      evaluated based on serum 25-hydroxyvitamin D (25-OHD). The aim of this article is
      to review the relationship of serum 25-OHD and osteoporotic fracture and the
      prevalence of 25-OHD insufficiency in patients with hip fracture, including
      assessment of nutritional status, oral status, activity, and dementia. We
      conclude that the serum 25-OHD level may be a useful index for risk of hip
      fracture in elderly people.

PMID- 17447112
TI  - Actin and microtubule cytoskeletons of the processes of 3D-cultured MC3T3-E1
      cells and osteocytes.
AB  - Cell shape is the most critical determinant of cell function and is potentially
      influenced by the organization of a cell's cytoskeletal components. It has been
      reported that three-dimensionally cultured osteoblasts have a morphology that
      closely resembles that of osteocytes, most notably including formation of
      processes. We have previously shown the critical differences between cytoskeletal
      components in osteoblasts and osteocytes in two-dimensional culture. We have now
      extended that investigation to the cytoskeletal components of 3D-cultured
      osteoblasts and osteocytes using 3D cultures of the osteoblast cell line, MC3T3
      E1, and primary osteocytes grown in collagen gel. Three-dimensional fluorescent
      image reconstructions for actin, fimbrin, alpha-actinin, myosin, tropomyosin, and
      microtubules were made using IMARIS software. Actin, fimbrin, alpha-actinin,
      myosin, and tropomyosin all appeared in the processes of both cell types, but
      fimbrin and myosin showed differences in their distribution patterns between cell
      types. Microtubules were limited in distribution to the proximal region of
      osteocyte processes but extended the entire length of MC3T3-E1 cell processes.
      Microtubules were essential for the integrity and formation of MC3T3-E1 cell
      processes, but osteocyte processes were dependent on actin. These results showed
      that there are significant differences between the actin and microtubule
      cytoskeletons in the processes of 3D-cultured MC3T3-E1 cells and in the processes
      of 3D-cultured primary osteocytes. These differences in the cytoskeleton of the
      processes of 3D-cultured osteoblasts and of osteocyte dendrites suggest that
      osteoblast processes may have a different functional role than the osteocyte
      dendritic network.

PMID- 17447113
TI  - Intragenic SNP haplotypes associated with 84dup18 mutation in TNFRSF11A in four
      FEO pedigrees suggest three independent origins for this mutation.
AB  - Familial expansile osteolysis (FEO) is a rare disorder causing bone dysplasia.
      The clinical features of FEO include early-onset hearing loss, tooth destruction,
      and progressive lytic expansion within limb bones causing pain, fracture, and
      deformity. An 18-bp duplication in the first exon of the TNFRSF11A gene encoding
      RANK has been previously identified in four FEO pedigrees. Despite having the
      identical mutation, phenotypic variations among affected individuals of the same
      and different pedigrees were noted. Another 18-bp duplication, one base proximal
      to the duplication previously reported, was subsequently found in two unrelated
      FEO patients. Finally, mutations overlapping with the mutations found in the FEO
      pedigrees have been found in ESH and early-onset PDB pedigrees. An Iranian FEO
      pedigree that contains six affected individuals dispersed in three generations
      has previously been introduced; here, the clinical features of the proband are
      reported in greater detail, and the genetic defect of the pedigree is presented.
      Direct sequencing of the entire coding region and upstream and downstream
      noncoding regions of TNFRSF11A in her DNA revealed the same 18-bp duplication
      mutation as previously found in the four FEO pedigrees. Additionally, eight
      sequence variations as compared to the TNFRSF11A reference sequence were
      identified, and a haplotype linked to the mutation based on these variations was
      defined. Although the mutation in the Iranian and four of the previously
      described FEO pedigrees was the same, haplotypes based on the intragenic SNPs
      suggest that the mutations do not share a common descent.

PMID- 17447114
TI  - Relative contribution of body composition to bone mineral density at different
      sites in men and women of South Korea.
AB  - We examined the relative contribution of body composition to bone mineral density
      (BMD) at various sites in 1406 Korean rural men and women, aged 19-80 years, from
      July to August 2004. The BMD was measured at peripheral (distal forearm and
      calcaneus) and central (lumbar spine at L1-L4, femoral neck, trochanter, and
      Ward's triangle) using dual-energy X-ray absorptiometry. In multivariate
      analyses, the linear regression models were adjusted for relevant covariates. In
      premenopausal women, only lean mass had a significant positive correlation with
      BMD at all sites. In postmenopausal women, fat mass was significantly positively
      correlated with BMD at all sites, except the Ward's triangle; fat mass was the
      only determinant of BMD at the lumbar, distal forearm, and calcaneus sites,
      whereas both lean and fat mass contributed to BMD at the hip, with the effect of
      lean mass being slightly greater than that of fat mass. In younger men, lean mass
      had a significant positive contribution to BMD at all sites, whereas fat mass
      appeared to contribute negatively to BMD at all sites, except the calcaneus. In
      older men, lean mass made a significant positive contribution to the BMD at all
      sites; fat mass also made a significant positive contribution to the BMD at the
      forearm and calcaneus. These data indicate that in the Korean rural population,
      lean mass may be an important determinant of the BMD, whereas fat mass may
      contribute positively to BMD only in postmenopausal women and older men.

PMID- 17447115
TI  - Levels of bone collagen markers in preterm infants: relation to antenatal
      glucocorticoid treatment.
AB  - Although the beneficial effects of antenatally administered glucocorticoids are
      well documented, data on the potential of adverse consequences are limited. The
      objective of this study was to determine the effects of antenatally administered
      glucocorticoids on biochemical markers of bone metabolism of 55 preterm infants
      with a gestational age of 24-34 weeks who were enrolled in the study. Neonates
      were divided into two groups according to antenatal exposure to corticosteroids.
      There were no significant differences between the groups in clinical
      characteristics and anthropometric variables. We studied blood levels of
      osteocalcin (OC), carboxy-terminal propeptide of type I procollagen (PICP), and
      carboxy-terminal telopeptide of type I collagen (ICTP) at the time of delivery,
      on postnatal day 10, and at 2 and 4 months of life. Comparing the groups, we
      found statistically significant reduction in PICP levels at birth in
      corticosteroid-exposed neonates (P < 0.05). The levels of bone markers increased
      progressively on the first days of life. There were no significant differences
      between groups in bone markers at 10 days or at 2 and 4 months of life. We found
      no significant difference for bone markers between groups of infants exposed to
      single or repeated maternal corticosteroid treatments. In summary, antenatal
      glucocorticoid treatments are suggested to have a negative impact on fetal bone
      formation as reflected by low PICP levels at birth. However, this negative effect
      on bone markers seems to be a temporary effect that subsides on the first days of
      life and afterward.

PMID- 17447116
TI  - Alendronate inhibits periprosthetic bone loss around uncemented femoral
      components.
AB  - Periprosthetic bone loss can be severe around the femoral component after
      uncemented arthroplasty. This study investigated the inhibitory effect of
      alendronate on periprosthetic bone loss. Seventeen patients underwent
      arthroplasty with an uncemented femoral component. Among them, 8 patients were
      given alendronate 5 mg once daily for 1 year (ALN group) and 9 patients received
      no pharmacotherapy (control group). Bone mineral density was measured in six
      periprosthetic zones by dual-energy X-ray absorptiometry at 1, 6, and 12 months
      after surgery. The average periprosthetic bone mineral density was 0.674-0.920
      g/cm(2) at 1 month after surgery. From 6 months onward, the absolute bone mineral
      density and the ratio relative to the 1-month value were significantly decreased
      in the proximal zones of the femur in the control group (the ratio decreased from
      0.817 to 0.769; P = 0.0040-0.0353). In the ALN group, however, the absolute and
      relative bone mineral density of the proximal femur remained unchanged for 12
      months. In the other femoral zones, the absolute and relative bone mineral
      density remained unchanged throughout the study in both groups. We concluded that
      alendronate significantly inhibited the decrease of periprosthetic bone mineral
      density in the proximal femur after uncemented arthroplasty.

PMID- 17447117
TI  - Identifying osteoporosis in a primary care setting with quantitative ultrasound:
      relationship to anthropometric and lifestyle factors.
AB  - Dual-energy X-ray absorptiometry (DXA), the "gold standard" for diagnosis of
      osteoporosis, is not recommended for population screening, and thus quantitative
      ultrasound (QUS) of the calcaneus is gaining popularity. The aim of the present
      study was to evaluate the relationship between QUS values and anthropometric and
      lifestyle factors, and to assess the diagnostic performance of QUS in predicting
      DXA-defined osteoporosis. Eight hundred and thirty-two women and 87 men aged 40
      88 years were included in the study. Anthropometric measurements, the
      questionnaire, and QUS and DXA measurements were performed by trained physicians.
      Both QUS and DXA T-scores were lower for women than for men. Postmenopausal women
      had significantly lower QUS T-scores compared to premenopausal women (P < 0.001).
      Age over 50, female sex, sedentary lifestyle, fracture history, presence of
      chronic disease, and > or =5 years since menopause were associated with QUS T
      scores lower than -1.00 by multivariate analysis. Low QUS T-scores were related
      to lack of direct sun exposure, high parity, fair skin color, and no education by
      univariate analysis (P < 0.005). A weak correlation was found between calcaneal
      QUS and DXA T-scores at lumbar spine (r = 0.310, P < 0.001) and femoral neck (r =
      0.288, P < 0.001). The sensitivity and specificity of the QUS test were 73.7% and
      57.4%, respectively, regarding the identification of osteoporotic patients. Lower
      QUS T-scores were associated with several osteoporotic risk factors, and the
      sensitivity and specificity of QUS for predicting DXA-defined osteoporosis were
      at optimum values at ages between 50 and 59 years. We conclude that, even though
      the accuracy of QUS for predicting DXA-defined osteoporosis is not remarkably
      high, it can be applied to identify subjects at risk in this age group in
      developing countries and rural districts who should be the focus of fracture
      prevention.

PMID- 17447118
TI  - The influence of serum ghrelin, IGF axis and testosterone on bone mineral density
      in boys at different stages of sexual maturity.
AB  - The aim of our study was to examine the relationship between bone mineral density
      (BMD) and serum ghrelin, insulin-like growth factor-1 (IGF-1), IGF-binding
      protein 3 (IGFBP-3), and testosterone levels in boys at different stages of
      puberty. The study included 60 healthy nonobese Estonian schoolboys at the age of
      10-18 years. Subjects were divided in three groups (20 boys in each) based on the
      results of self-assessment using illustrated questionnaire of pubertal stage (G1,
      I; G2-G3, II; G3-G4, III). Morning fasting blood samples were collected for
      analysis of ghrelin, testosterone, IGF-1, and IGFBP-3. Total body BMD, lumbar
      BMD, lumbar apparent volumetric BMD (BMAD), and bone mineral content (BMC) were
      measured by DXA. Serum testosterone concentration was the most important
      biochemical predictor of BMD in the total group, explaining 48.8% of variability
      in total body BMD, 51.4% in lumbar BMD, and 36.8% in lumbar BMAD. Body mass and
      height were both related to BMD and BMC throughout puberty. The serum IGF-1/IGFBP
      3 ratio was correlated with serum testosterone (r = 0.69) and ghrelin (r = -0.58)
      levels, but also with total BMD (r = 0.39), lumbar BMD (r = 0.42; P < 0.001 in
      all cases), BMAD (r = 0.29; P < 0.01), and total BMC (r = 0.48; P < 0.001). We
      conclude that serum testosterone concentration and serum IGF-1/IGFBP-3 molar
      ratio are the major determinants of bone mineral density in boys at different
      pubertal stages. Serum ghrelin concentration did not appear to have a direct
      independent effect on BMD. If present, the association may be mediated through
      sex hormones and the GH-IGF-I axis.

PMID- 17447119
TI  - Vitamin D deficiency in the elderly in Athens, Greece.
AB  - Vitamin D deficiency characterized by low 25-hydroxyvitamin D [25(OH)D] levels
      has been found to be prevalent among the elderly in many regions of the world. To
      investigate the vitamin status in elderly community-living persons in Athens, we
      measured 25(OH)D and parathyroid hormone (PTH) in elderly persons and young blood
      donors during the winter and summer. The changes in these parameters in a
      subgroup of the elderly were studied longitudinally. The blood donors had mean
      25(OH)D levels similar in winter and summer and twice as high in winter compared
      to the elderly. At the end of the winter, about 20% of the elderly had severe
      vitamin D deficiency, with 25(OH)D below 25 nmol/l, and only 6.5% could be judged
      as vitamin D sufficient with values above 80 nmol/l. The situation improved
      during summer, although 64.8% of the elderly continued to have levels below 80
      nmol/l. Mean plasma PTH in the elderly in summer was not different from that of
      blood donors; however, it was doubled during the winter. Regression of PTH on
      25(OH)D demonstrated that PTH starts to rise when 25(OH)D falls below
      approximately 80 nmol/l. We conclude that severe vitamin deficiency associated
      with secondary hyperparathyroidism is not uncommon in the elderly in Athens
      during the winter; it subsides during summer, although only one-third of the
      elderly population attain vitamin D sufficiency during summer. We found that a
      threshold value of 25(OH)D exists at approximately 80 nmol/l, below which
      secondary hyperparathyroidism ensues, as described previously.

PMID- 17447120
TI  - Relationships between silicon content and glutathione peroxidase activity in
      tissues of rats receiving lithium in drinking water.
AB  - Lithium salts are widely used in psychiatry, but their presence in organism can
      result in both beneficial and adverse effects. Silicon, the third most abundant
      trace element in humans as well as antioxidant enzyme glutathione peroxidase
      (GPx) play important roles in organism. The disturbance of their level can cause
      severe disorders. The aim of our work was to evaluate the influence of Li2CO3
      administration in drinking water for a period of 4 weeks on Si content and GPx
      activity in the tissues of liver, kidney, brain and femoral muscle in rats. The
      concentrations of provided solutions were 0.7, 1.4, 2.6, 3.6, 7.1 and 10.7 mmol
      Li+ x dm-3. GPx activity was decreased versus control as a consequence of Li
      treatment, particularly in kidney and brain. This effect could be suggested to
      contribute to renal abnormalities which could occur during Li therapy. Si tissue
      level was significantly enhanced versus control in liver and femoral muscle in
      groups receiving high Li doses. In brain no well-marked changes were observed,
      whereas in kidney we observed the depletion in low-Li-groups, restoration of Si
      level in higher-Li-groups and unexpected decrease in the highest-Li-group.
      Positive correlations between Si content and GPx activity in the tissues of
      kidney (r = 0.677) and brain (r = 0.790) as well as negative correlation (r = 
      0.819) in femoral muscle were found. We consider that our results give some
      reason for suggesting that monitoring of silicon level in patients undergoing Li
      therapy could be recommended. However, more investigations should be performed,
      particularly regarding the relationships between Si and GPx in blood and urine Si
      excretion during lithium administration.

PMID- 17447121
TI  - Effects of carrier on disposition and antitumor activity of intraperitoneal
      Paclitaxel.
AB  - PURPOSE: The rationale for intraperitoneal (IP) chemotherapy is to expose
      peritoneal tumors to high drug concentrations. While multiple phase III trials
      have established the significant survival advantage by adding IP therapy to
      intravenous therapy in optimally debulked ovarian cancer patients, the use of IP
      chemotherapy is limited by the complications associated with indwelling catheters
      and by the local chemotherapy-related toxicity. The present study evaluated the
      effects of drug carrier on the disposition and efficacy of IP paclitaxel, for
      identifying strategies for further development of IP treatment. MATERIALS AND
      METHODS: Three paclitaxel formulations, i.e., Cremophor micelles, Cremophor-free
      paclitaxel-loaded gelatin nanoparticles and polymeric microparticles, were
      evaluated for peritoneal targeting advantage and antitumor activity in mice after
      IP injection. Whole body autoradiography and scanning electron microscopy were
      used to visualize the spatial drug distribution in tissues. A kinetic model,
      depicting the multiple processes involved in the peritoneal-to-plasma transfer of
      paclitaxel and its carriers, was established to determine the mechanisms by which
      a drug carrier alters the peritoneal targeting advantage. RESULTS:
      Autoradiographic results indicated that IP injection yielded much higher
      paclitaxel concentrations in intestinal tissues relative to intravenous
      injection. Compared to the Cremophor and nanoparticle formulations, the
      microparticles showed slower drug clearance from the peritoneal cavity, slower
      absorption into the systemic circulation, longer residence time, 10- to 45-times
      greater peritoneal targeting advantage and approximately 2-times longer increase
      in survival time (p < 0.01 for all parameters). CONCLUSIONS: Our results indicate
      the important roles of drug carrier in determining the peritoneal targeting
      advantage and antitumor activity of IP treatment.

PMID- 17447122
TI  - Decreased proliferation and erythroid differentiation of K562 cells by siRNA
      induced depression of OCTN1 (SLC22A4) transporter gene.
AB  - PURPOSE: Recently, it was reported that OCTN1 transporter (SLC22A4) is associated
      with rheumatoid arthritis (RA) and Crohn's disease. Additionally, we reported
      that OCTN1 is expressed in hematopoietic cells, preferentially in erythroid
      cells. Accordingly, we assessed the physiological role of OCTN1 by examining the
      effect of knockdown of OCTN1 in blood cells using siRNA method. MATERIALS AND
      METHODS: Vector-based short hairpin RNA (shRNA) was used to establish K562 cell
      line which shows stably decreased expression of OCTN1. The characteristic of
      knockdown of OCTN1 in K562 cells was investigated by cell proliferation, cell
      differentiation, and uptake of ergothioneine that is a good substrate of OCTN1.
      RESULTS: Several clones of K562 cells exhibited significantly reduced expression
      of OCTN1 mRNA and protein. They also showed a decreased growth rate and butyrate
      dependent differentiation to erythrocytes compared with control-vector
      transfected cells. In addition, uptake of [(3)H]ergothioneine by K562 cells
      suggested that Na(+)-dependent and high-affinity transporter which is similar to
      the characteristics of OCTN1 is functional. Moreover, uptake of ergothioneine by
      K562 cells which exhibit decreased-expression of OCTN1 was decreased in
      comparison with wild type K562 cells. CONCLUSIONS: It was suggested that OCTN1 is
      involved in the transport of physiological compounds that are important for cell
      proliferation and erythroid differentiation.

PMID- 17447123
TI  - Chemotaxis of the pinewood nematode, Bursaphelenchus xylophilus, to volatiles
      associated with host pine, Pinus massoniana, and its vector Monochamus
      alternatus.
AB  - The pinewood nematode (PWN), Bursaphelenchus xylophilus, the most important
      invasive species in pine forests of Asia, is transported to new pine hosts by
      beetles of the genus Monochamus. Third-stage dispersal juveniles (J(III))
      aggregate in pupal chambers around the vector as it matures. We demonstrated that
      the ratio of three terpenes (alpha-pinene, beta-pinene, and longifolene at
      1:2.7:1.1) released by larval Monochamus alternatus strongly attract J(III),
      whereas the different ratio (1:0.1:0.01) of these three terpenes found in healthy
      xylem of Pinus massoniana attracts only the propagative stage (J(n)) of the
      nematode. We suggest that the volatiles produced by the host plants could be the
      basis of a chemoecological relationship between plant parasitic nematodes and
      their vector insects. Capture of J(III) with terpene-baited trap tubes deployed
      for 2 hr in the field was demonstrated. This technique may lead to the
      development of rapid sampling methodologies for use at either ports-of-entry or
      in the field.

PMID- 17447124
TI  - Engineered telomeres in transgenic Xenopus laevis.
AB  - The expanding roles of telomeres in epigenetic gene regulation, nuclear
      organization, and human disease have necessitated the establishment of model
      organisms in which to study telomere function under normal developmental
      conditions. We present an efficient system for generating numerous vertebrate
      animals containing engineered telomeres using a Xenopus laevis transgenesis
      technique. Our results indicate Xenopus zygotes efficiently recognize telomeric
      repeats at chromosome break points and form telomeric complexes thus generating a
      new telomere. The resulting transgenic animals progress through normal
      development and successfully metamorphose into froglets despite the chromosome
      breakage. Overall, this presents an efficient mechanism for generating engineered
      telomeres in a vertebrate system and provides an opportunity to investigate
      epigenetic aspects of telomere function during normal vertebrate development.

PMID- 17447125
TI  - Detection and analysis of protein aggregation with confocal single molecule
      fluorescence spectroscopy.
AB  - The misfolding and aggregation of proteins is a common phenomenon both in the
      cell, in in vitro protein refolding, and the corresponding biotechnological
      applications. Most importantly, it is involved in a wide range of diseases,
      including some of the most prevalent neurodegenerative disorders. However, the
      range of methods available to analyze this highly heterogeneous process and the
      resulting aggregate structures has been very limited. Here we present an approach
      that uses confocal single molecule detection of FRET-labeled samples employing
      four detection channels to obtain information about diffusivity, anisotropy,
      fluorescence lifetimes and Forster transfer efficiencies from a single
      measurement. By combining these observables, this method allows the separation of
      subpopulations of folded and misfolded proteins in solution with high sensitivity
      and a differentiation of aggregates generated under different conditions. We
      demonstrate the versatility of the method with experiments on rhodanese, an
      aggregation-prone two-domain protein.

PMID- 17447126
TI  - Nitric oxide increases oxidative phosphorylation efficiency.
AB  - We have studied the effect of nitric oxide (NO) and potassium cyanide (KCN) on
      oxidative phosphorylation efficiency. Concentrations of NO or KCN that decrease
      resting oxygen consumption by 10-20% increased oxidative phosphorylation
      efficiency in mitochondria oxidizing succinate or palmitoyl-L-carnitine, but not
      in mitochondria oxidizing malate plus glutamate. When compared to malate plus
      glutamate, succinate or palmitoyl-L-carnitine reduced the redox state of
      cytochrome oxidase. The relationship between membrane potential and oxygen
      consumption rates was measured at different degrees of ATP synthesis. The use of
      malate plus glutamate instead of succinate (that changes the H(+)/2e(-)
      stoichiometry of the respiratory chain) affected the relationship, whereas a
      change in membrane permeability did not affect it. NO or KCN also affected the
      relationship, suggesting that they change the H(+)/2e(-) stoichiometry of the
      respiratory chain. We propose that NO may be a natural short-term regulator of
      mitochondrial physiology that increases oxidative phosphorylation efficiency in a
      redox-sensitive manner by decreasing the slipping in the proton pumps.

PMID- 17447127
TI  - Catheter ablation of atrial fibrillation in patients with hyperthyroidism.
AB  - AIMS: To study the clinical efficacy of catheter ablation for treating patients
      with hyperthyroidism-related atrial fibrillation (AF). MATERIALS AND METHODS: The
      study involved 16 patients (12 males; age, 59.8 +/- 11.3 years) with
      hyperthyroidism-related AF, who had all been euthyroid for more than 3 months but
      still suffered from highly symptomatic and antiarrhythmia drug (AAD)-refractory
      AF. Circumferential pulmonary vein ablation (CPVA) guided by a 3-D mapping system
      was carried out to encircle the ipsilateral pulmonary veins (PVs) with a
      procedural endpoint of continuity of the circular lesions and PV isolation.
      Success was defined as the absence of any atrial tachyarrhythmia (ATa) off AADs
      beyond the first 3 months after the procedure. RESULTS: CPVA was safely carried
      out in each of the 16 patients without any complications. PV isolation was
      achieved in all the treated PVs. After a mean follow-up of 15.8 +/- 11.8 (range,
      6-55) months, 9 patients (56%) were free of ATa without any AADs beyond the first
      3 months. AF relapsed in the remaining 7 patients, among whom 4 responded to AAD
      therapy and 3 were totally unresponsive. CONCLUSION: For patients suffering
      hyperthyroidism-related AF, CPVA guided by a 3-D mapping system could represent
      one of the therapeutic options.

PMID- 17447128
TI  - Using multiple buddy wires to facilitate left ventricular lead advancement in
      cardiac resynchronization therapy.
AB  - Left ventricular lead positioning is always the critical step in cardiac
      resynchronization therapy because of the complex anatomy of coronary sinus
      branches. We describe the case of a 46-year-old man with dilated cardiomyopathy
      and complete left bundle branch block presenting with heart failure. The placing
      of the left ventricular lead into the posterolateral branch was hampered by an
      angulated portion at the proximal branch even with the assistance of anchor wire
      technique and one to two additional parallel wires' support. The use of three
      buddy wires facilitated the advancement of the left ventricular lead.

PMID- 17447129
TI  - Roles of IA and morphology in action potential propagation in CA1 pyramidal cell
      dendrites.
AB  - Dendrites of CA1 pyramidal cells of the hippocampus, along with those of a wide
      range of other cell types, support active backpropagation of axonal action
      potentials. Consistent with previous work, recent experiments demonstrating that
      properties of synaptic plasticity are different for distal synapses, suggest an
      important functional role of bAPs, which are known to be prone to failure in
      distal locations. Using conductance-based models of CA1 pyramidal cells, we show
      that underlying "traveling wave attractors" control action potential propagation
      in the apical dendrites. By computing these attractors, we dissect and quantify
      the effects of I(A) channels and dendritic morphology on bAP amplitudes. We find
      that non-uniform activation properties of I(A) can lead to backpropagation
      failure similar to that observed experimentally in these cells. Amplitude of
      forward propagation of dendritic spikes also depends strongly on the activation
      dynamics of I(A). I(A) channel properties also influence transients at dendritic
      branch points and whether or not propagation failure results. The branching
      pattern in the distal apical dendrites, combined with I(A) channel properties in
      this region, ensure propagation failure in the apical tuft for a large range of
      I(A) conductance densities. At the same time, these same properties ensure
      failure of forward propagating dendritic spikes initiated in the distal tuft in
      the absence of some form of cooperativity of synaptic activation.

PMID- 17447130
TI  - Narrative role-taking in autism.
AB  - Are children with autism able to adopt, and shift among, the psychological
      perspectives of different people? Fifteen children with autism and 15 without
      autism, matched for chronological age and verbal ability, were given Feffer's
      (1970) role-taking task in which they were asked to tell and then re-tell stories
      from different protagonists' perspectives. The children with autism understood
      the task, adjusted narratives according to alternative viewpoints, and were
      similar to control participants in their use of mental state terms. Despite this,
      the children with autism achieved significantly lower scores for adopting
      different figures' perspectives, and for shifting among complementary viewpoints.
      The results illustrate aspects of social-cognitive impairment that extend beyond
      the children's limitations in 'theory of mind' understanding.

PMID- 17447131
TI  - A prospective investigation of acceptance and control-oriented coping with
      chronic pain.
AB  - Historically, investigations of coping with chronic pain primarily have sought
      methods for gaining greater control over pain and pain-related distress.
      Recently, it has been suggested to expand the framework of coping so that control
      efforts are redirected from circumstances where they fail, and so that coping can
      more explicitly incorporate potentially more practical and flexible notions of
      acceptance. The purpose of the present study was to evaluate the role of control
      oriented and acceptance-oriented coping responses for patient functioning using a
      prospective design. Participants included 120 adult patients with chronic pain
      who completed measures of coping, pain, disability, depression, and pain-related
      anxiety at two time points, separated by an average of 3.7 months (SD = 2.6
      months). Factor analyses revealed four factors within the coping data: Pain
      Management, Pain Control, Help Seeking, and Activity Persistence. A series of
      correlation and linear regression analyses was performed to assess the relations
      of these factors at initial assessment to functioning later in time. In general,
      Activity Persistence was associated with better functioning over time while
      control-oriented responses were associated with greater difficulty. The factor
      representing more or less traditional pain management methods showed surprisingly
      limited relations with aspects of patient functioning. Analyses of concurrent
      change in coping and functioning highlighted a unique, apparently unhelpful, role
      of Pain Control. These results support the inclusion of contextual acceptance
      related processes in current frameworks for understanding adjustment to chronic
      pain.

PMID- 17447132
TI  - Unstable housing as a factor for increased injection risk behavior at US syringe
      exchange programs.
AB  - OBJECTIVE: To assess variation in injection risk behavior among unstably
      housed/homeless injecting drug users (IDUs) across programs in a national sample
      of US syringe exchange programs. METHODS: About 23 syringe exchange programs were
      selected through stratified random sampling of moderate to very large US syringe
      exchange programs operating in 2001-2005. Subjects at each program were randomly
      sampled. Risk behavior interviews were collected using audio-computer assisted
      self-interviewing (A-CASI). "Unstable housing/homelessness" was operationally
      defined as having lived "on the street or in a shanty" or "living in a shelter or
      single room occupancy hotel (SRO)" at any time in the 6 months prior to the
      interview. "Receptive sharing" was operationally defined as having injected with
      a needle or syringe that "had been used by someone else" in the 30 days prior to
      the interview. Six very large and nine moderate-to-large programs had at least 50
      subjects who reported unstable housing, and these 15 programs were used in the
      analyses. RESULTS: There was considerable variation among the 15 programs in the
      percentages of unstably housed participants (range from 35 to 74%, P < 0.0001),
      and in the percentages of unstably housed participants who reported receptive
      sharing (range from 8 to 52%, P < 0.0001). At each of the 15 programs, unstably
      housed exchange participants were approximately twice as likely to report
      receptive sharing than were stably housed participants. The weighted mean odds
      ratio was 2.02, 95% confidence interval, 1.68-2.41 (random effects model) and
      there was no statistically significant variation in these odds ratios. Across the
      15 programs, receptive sharing among unstably housed participants was highly
      correlated with receptive sharing among stably housed participants (r = 0.95, P <
      0.001, 90% of variance among unstably housed "explained" by variance among stably
      housed). CONCLUSIONS: The programs clearly differ in the extent to which they are
      attracting unstably housed IDUs as participants. The consistency of more frequent
      injection risk behavior among unstably housed exchange participants and the lack
      of significant variation in the odds ratios for increased injection risk suggests
      that none of the programs were "better" or "worse" at reducing injection risk
      behavior among unstably housed participants. Reduction in injecting risk behavior
      among syringe exchange participants may require greater efforts to provide stable
      housing or the development of dramatically new interventions to reduce injecting
      risk behavior among IDUs with persistent unstable housing.

PMID- 17447133
TI  - Building contexts that support effective community responses to HIV/AIDS: a South
      African case study.
AB  - In this paper we discuss our conceptualisation of a 'health-enabling social
      environment', and some of the strategies we are currently using to build social
      contexts most likely to support effective HIV/AIDS management in southern Africa.
      In developing these ideas, we draw on our on-going collaboration with residents
      of Entabeni, a remote rural community in South Africa where 43% of pregnant women
      are HIV positive. The aim of this collaboration is to facilitate contextual
      changes that will enable more effective community-led HIV/AIDS management in an
      isolated area where people have little or no access to formal health or welfare
      support, and where HIV/AIDS is heavily stigmatised. We give an account of the
      three phases of collaboration to date. These include research; the dissemination
      of findings and community consultation about the way forward; preliminary project
      activities (skills training for volunteer health workers; partnership building
      and a youth rally) as a way of illustrating what we believe are six key
      strategies for facilitating the development of 'AIDS-competent' communities:
      building knowledge and basic skills; creating social spaces for dialogue and
      critical thinking; promoting a sense of local ownership of the problem and
      incentives for action; emphasising community strengths and resources; mobilising
      existing formal and informal local networks; and building partnerships between
      marginalized communities and more powerful outside actors and agencies, locally,
      nationally and internationally. We discuss some of the triumphs and trials of
      this work, concluding with a discussion of the need to set realistic goals when
      working at the community level in highly conservative patriarchal communities to
      tackle problems which may be shaped by economic and political processes over
      which local people have little control.

PMID- 17447134
TI  - Capturing system level activities and impacts of mental health consumer-run
      organizations.
AB  - Since the 1970s mental health consumer-run organizations have come to offer not
      only mutual support, but they have also adopted agendas for broader social
      change. Despite an awareness of the need for system level efforts that create
      supportive environments for their members, there has been limited research
      demonstrating how their system level activities can be documented or their
      impacts evaluated. The purpose of this paper is to feature a method of evaluating
      systems change activities and impacts. The paper is based on a longitudinal study
      evaluating four mental health consumer-run organizations in Ontario, Canada. The
      study tracked system level activities and impacts using both qualitative and
      quantitative methodologies. The article begins by describing the development and
      implementation of these methods. Next it offers a critical analysis of the
      methods used. It concludes by reflecting on three lessons learned about capturing
      system level activities and impacts of mental health consumer-run organizations.

PMID- 17447135
TI  - Rapid activation of the extracellular signal-regulated kinase 1/2 (ERK1/2)
      signaling pathway by electroconvulsive shock in the rat prefrontal cortex is not
      associated with TrkB neurotrophin receptor activation.
AB  - 1. Emerging evidence indicates that brain-derived neurotrophic factor (BDNF) and
      its receptor TrkB play important roles in the mechanism of action of
      electroconvulsive shock (ECS) treatment. ECS produces a significant increase in
      brain BDNF synthesis together with a variety of neuroplastic changes including
      neurogenesis and axonal sprouting in the rodent brain, which is believed to be
      associated to the antidepressant effect of ECS. ERK1/2 (extracellular signal
      regulated kinase-1/2) and Akt (protein kinase B), both intracellular signaling
      molecules being linked to neurotrophin signaling and synthesis, are important
      pathways triggered by TrkB autophosphorylation. 2. We have previously observed
      that chemical antidepressants induce a rapid activation of TrkB signaling in the
      rodent prefrontal cortex (PFC), which is likely a consequence of the stimulatory
      effect of antidepressants on BDNF synthesis. However, it is not known whether ECS
      triggers TrkB autophosphorylation and if any ECS-induced effect on TrkB function
      may be associated with the activation of the ERK1/2 and Akt pathways. 3. The
      present study assayed the phosphorylation levels of TrkB, ERK1/2, and Akt in the
      PFC of sham and ECS-treated rats. While the TrkB autophosphorylation (pTrkB)
      levels were decreased 30 min after both acute and chronic ECS, no change in pTrkB
      levels were observed at any other time points measured. In contrast, acute but
      not chronic ECS, transiently induced a very rapid and robust hyperphosphorylation
      of ERK1/2. Akt phosphorylation levels remained unchanged following acute or
      chronic ECS. Hence, although ECS effectively stimulates the ERK1/2 pathway in the
      PFC, this effect does not appear to involve upstream activation of TrkB.

PMID- 17447137
TI  - Vasodilators in acute heart failure.
AB  - Most patients with acute heart failure present with increased left ventricular
      filling pressure and high or normal blood pressure; only a minority present with
      cardiogenic shock. In this context, therapy with vasodilators in the acute
      setting can improve both hemodynamics and symptoms. Vasodilators are usually
      given in conjunction with diuretics, although much of the acute effect of loop
      diuretics may be due to venodilation. Currently available agents include
      nitroglycerin, nitroprusside, and nesiritide. Nitroglycerin relieves pulmonary
      congestion primarily through direct venodilation, but may dilate coronary
      arteries and increase collateral blood flow at higher doses, an effect desirable
      in patients with ischemia. Tachyphylaxis may develop, necessitating incremental
      dosing. The major adverse effects of nitrates are hypotension and headache.
      Nitroprusside is a balanced arterial and venous vasodilator with a very short
      half-life, facilitating rapid titration. Afterload reduction lowers blood
      pressure and can increase stroke volume. The major complications of nitroprusside
      therapy are hypotension, and toxicity from accumulation of cyanide or
      thiocyanate, usually in patients with renal insufficiency treated for more than
      24 h. Nesiritide, a recombinant form of human B-type natriuretic peptide (BNP),
      is a venous and arterial vasodilator that may also potentiate the effect of
      concomitant diuretics. Hypotension is the most common side effect. In addition,
      meta-analyses have suggested that nesiritide may worsen renal function and
      decrease survival at 30 days compared to conventional therapies. Resolution of
      these concerns awaits completion of appropriately powered prospective clinical
      trials. Angiotensin-converting enzyme (ACE) inhibitors have vasodilatory effects,
      but intravenous infusion of enalapril within 24 h of ischemic chest pain is not
      recommended. Oral ACE inhibition may be used to reduce afterload in other
      settings if blood pressure permits. Use of calcium antagonists in acute heart
      failure is not recommended.

PMID- 17447136
TI  - Therapeutic and diagnostic role of electrical devices in acute heart failure.
AB  - Electrical devices, Cardiac Resynchronization Therapy (CRT) pacemakers, the
      Implantable Cardiac Defibrillator (ICD) and a combination of both, constitute an
      important line of treatment in the therapy of moderate to severe chronic heart
      failure. The effectiveness of these devices in the treatment of acute
      decompensated heart failure has yet to be systematically evaluated. However, the
      beneficial clinical effects of CRT translate into a marked reduction of heart
      failure-related hospitalization. Devices also offer unique diagnostic
      applications by continuous measurement of clinically useful physiological
      parameters over time. Of particular interest, monitoring of intrathoracic
      impedance and right ventricular pressures allows to detect changes in volume load
      in an early stage prior to the development of clinical symptoms. This information
      could be helpful to stop further progression to acute cardiac decompensation and
      to avoid hospitalization and acute clinical events. Using modern
      telecommunication technology, patients can also be remotely monitored in their
      daily living environment. In consequence, the incorporation of device technology
      into heart failure management programs calls for a close cooperation between
      heart failure specialists and electrophysiologists. This review addresses
      therapeutic and diagnostic aspects of device therapies in the context of acute
      heart failure.

PMID- 17447138
TI  - Diuretics for the treatment of acute decompensated heart failure.
AB  - Diuretics have been a mainstay for the treatment of acute decompensated heart
      failure (ADHF) for the past four decades, though their short-term gains have been
      questioned recently given their potential long-term deleterious systemic effects.
      The methods of diuretic administration as well as the optimal dosing regimen of
      these agents are both areas that have been increasingly coming under scrutiny.
      The lack of rigorous clinical trials examining diuretic use in ADHF, however, has
      led to a general adoption of non-evidence based treatment algorithms for this
      patient population. Though the use of intravenous vasodilators for the treatment
      of decompensated heart failure has grown tremendously over the last few years,
      the fact remains that diuretics are still indispensable for alleviating
      congestive symptoms. Given this reality and until further information is
      available about the most ideal utilization of these medications, diuretics will
      continue to represent a double-edged sword for physicians treating this disease
      process.

PMID- 17447139
TI  - Haemodynamic monitoring in acute heart failure.
AB  - Acute Heart Failure is a major cause of hospitalisation, with a rate of death and
      complications. New guidelines have been developed in order to diagnose and treat
      this disease. Despite these efforts pathophysiology and treatments options are
      still limited. There is agreement among the experts that increasing the cardiac
      output and the stroke volume without fluid overloading the patient should be the
      goal of every treatment. Despite this, there is no agreement on how to monitor
      the cardiac function and how to follow it after a therapeutic intervention. In
      other fields of critical care cardiovascular monitoring and application of early
      goal directed protocols showed benefits. This review explores the available
      possibilities of how to monitor the cardiac function in Acute Heart Failure.
      Standard and more advanced techniques are presented. Cardiac output monitors from
      the pulmonary artery catheter to the pulse pressure analysis and Doppler
      techniques are discussed, with focus on this specific clinical setting.
      Undoubtedly monitoring is valuable tool, but without a protocol of how to
      manipulate the haemodynamics, no monitor will prove alone to be beneficial.
      Haemodynamic driven early goal directed therapy are largely awaited in this field
      of medicine.

PMID- 17447140
TI  - What's behind the decline? The role of white matter in brain aging.
AB  - The specific molecular events that underlie the age-related loss of cognitive
      function are poorly understood. Although not experimentally substantiated, age
      dependent neuronal loss has long been considered central to age-related cognitive
      decline. More recently, age-related changes in brain white matter have taken
      precedence in explaining the steady decline in cognitive domains seen in non
      diseased elderly. Characteristic alterations in the ultrastructure of myelin
      coupled with evidence of inflammatory processes present in the white matter of
      several different species suggest that specific molecular events within brain
      white matter may better explain observed pathological changes and cognitive
      deficits. This review focuses on recent evidence highlighting the importance of
      white matter in deciphering the course of "normal" brain aging.

PMID- 17447141
TI  - A simplified method for isolating highly purified neurons, oligodendrocytes,
      astrocytes, and microglia from the same human fetal brain tissue.
AB  - Elucidation of the underlying pathogenic mechanisms leading to apoptosis of
      neurons and oligodendrocytes and activation of microglia and astrocytes in
      different neurodegenerative and neuroinflammatory disorders remains a challenge
      in neuroscience. In order to overcome the challenge and find out therapeutic
      remedies, it is important to study live and death processes in each and every
      cell type of the brain. Here we present a protocol of isolating highly purified
      microglia, astrocytes, oligodendrocytes, and neurons, all four major cell types
      of the CNS, from the same human fetal brain tissue. As found in vivo, these
      primary neurons and oligodendroglia underwent apoptosis and cell death in
      response to neurodegenerative challenges. On the other hand, astroglia, and
      microglia, cells that do not die in neurodegenerative brains, became activated
      after inflammatory challenge. The availability of highly purified human brain
      cells will increase the possibility of developing therapies for different
      neurodegenerative disorders.

PMID- 17447142
TI  - Time-dependent alteration of cytoskeletal proteins in cerebral cortex of rat
      during 2,5-hexanedione-induced neuropathy.
AB  - To investigate the mechanisms of the axonopathy induced by 2,5-hexanedione (2,5
      HD), male Wistar rats were administered at a dosage of 400 mg/kg/day 2,5-HD (five
      times per week). The rats produced a slightly, moderately, or severely abnormal
      neurological changes, respectively, after 2, 4, or 8 weeks of treatment. The
      cerebrums were Triton-extracted and ultracentrifuged to yield a pellet fraction
      and a corresponding supernatant fraction. The relative levels of six cytoskeletal
      proteins (NF-L, NF-M, NF-H, alpha-tubulin, beta-tubulin, and beta-actin) in both
      fractions were determined by immunoblotting. The results showed that NFs content
      in HD-treated rats demonstrated a progressive decline as the intoxication of HD
      continued. As for microtubule proteins, the levels of alpha-tubulin and beta
      tubulin demonstrated some inconsistent changes. The content of alpha-tubulin kept
      unchangeable, while the content of beta-tubulin increased significantly at the
      late stage of HD exposure. Furthermore, the content of beta-actin in both
      fractions remained unaffected throughout the study. These findings suggest that
      HD intoxication resulted in a progressive decline of NFs, which was highly
      correlated with the development of HD-induced neuropathy.

PMID- 17447143
TI  - Gender differences in the media interviews of Bill and Hillary Clinton.
AB  - Does gender make a difference in the way politicians speak and are spoken to in
      public? This paper examines perspective in three television interviews and two
      radio interviews with Bill Clinton in June 2004 and in three television
      interviews and two radio interviews with Hillary Clinton in June 2003 with the
      same interviewers. Our perspectival approach assumes that each utterance has a
      dialogically constructed point of view. Earlier research has shown that markers
      of conceptual orality and literacy as well as referencing (name and pronoun use
      for self and other reference) do reflect perspective. This paper asks whether
      perspective is gendered. Our data analysis demonstrates that some markers of
      perspective show gender differences while others do not. Those that do include
      the number of syllables spoken by each interlocutor, referencing, the use of the
      intensifier so, the use of the hedge you know, the use of non-standard
      pronunciations, turn transitions, and lastly the use of laughter.

PMID- 17447144
TI  - Stromal induction of breast cancer: inflammation and invasion.
AB  - Many investigations of cancer development have pursued the mechanisms by which
      genetic mutations stimulate tumor development through activation of oncogenes or
      loss of tumor suppressor genes. However, there is an increasing awareness that
      signals provided by the stroma can induce the genetic alterations that underlie
      tumor formation, can stimulate tumor growth and progression, and can dictate both
      therapeutic response and ultimate clinical outcome. This principle is
      particularly clear in breast cancer, where recent investigations using
      sophisticated three-dimensional cell culture models and transgenic animals have
      been used to define how altered signals from the microenvironment contribute to
      breakdown of tissue structure, increased cellular proliferation, and transition
      to the malignant phenotype. We review here recent studies identifying new roles
      for cancer-associated fibroblasts in promoting tumor progression, through
      stimulation of inflammatory pathways and induction of extracellular matrix
      remodelling proteases. These studies identify mechanisms by which development of
      a reactive tumor stroma causes mammary hyperproliferation, progression to
      fibrosis, development of neoplasia, increasing invasiveness, and eventual
      metastasis, and how intervention in these processes may provide new avenues for
      therapy.

PMID- 17447145
TI  - Deprivation indices, population health and geography: an evaluation of the
      spatial effectiveness of indices at multiple scales.
AB  - Area-based deprivation indices (ABDIs) have become a common tool with which to
      investigate the patterns and magnitude of socioeconomic inequalities in health.
      ABDIs are also used as a proxy for individual socioeconomic status. Despite their
      widespread use, comparably less attention has been focused on their geographic
      variability and practical concerns surrounding the Modifiable Area Unit Problem
      (MAUP) than on the individual attributes that make up the indices. Although scale
      is increasingly recognized as an important factor in interpreting mapped results
      among population health researchers, less attention has been paid specifically to
      ABDI and scale. In this paper, we highlight the effect of scale on indices by
      mapping ABDIs at multiple census scales in an urban area. In addition, we compare
      self-rated health data from the Canadian Community Health Survey with ABDIs at
      two census scales. The results of our analysis confirm the influence of spatial
      extent and scale on mapping population health-with potential implications for
      health policy implementation and resource distribution.

PMID- 17447146
TI  - Achieving health equity in urban settings.

PMID- 17447147
TI  - Beliefs that condoms reduce sexual pleasure-gender differences in correlates
      among heterosexual HIV-positive injection drug users (IDUs).
AB  - Studies consistently find that negative condom beliefs or attitudes are
      significantly associated with less condom use in various populations, including
      HIV-positive injection drug users (IDUs). As part of efforts to reduce sexual
      risk among HIV-positive IDUs, one of the goals of HIV interventions should be the
      promotion of positive condom beliefs. In this paper we sought to identify the
      correlates of negative condom beliefs and examined whether such correlates varied
      by gender, using a subsample (those with an opposite-sex main partner; n = 348)
      of baseline data collected as part of a randomized controlled study of HIV
      positive IDUs. In multivariate analyses, we found more significant correlates for
      women than for men. With men, perception that their sex partner is not supportive
      of condom use (negative partner norm) was the only significant correlate (Beta = 
      0.30; p < 0.01; R (2) = 0.18). Among women, negative partner norm (Beta = -0.18;
      p < 0.05); having less knowledge about HIV, STD, and hepatitis (Beta = -0.16; p <
      0.05); lower self-efficacy for using a condom (Beta = -0.40; p < 0.01); and more
      episodes of partner violence (Beta = 0.15; p < 0.05) were significantly
      associated with negative condom beliefs (R (2) = 0.36). These findings suggest
      important gender-specific factors to consider in interventions that seek to
      promote positive condom beliefs among HIV-positive IDUs.

PMID- 17447148
TI  - Agreement of diagnosis and its date for hematologic malignancies and solid tumors
      between medicare claims and cancer registry data.
AB  - PURPOSE: Claims data may be a suitable source studying associations between drugs
      and cancer. However, linkage between cancer registry and claims data including
      pharmacy-dispensing information is not always available. We examined the accuracy
      of claims-based definitions of incident cancers and their date of diagnosis.
      METHODS: Four claims-based definitions were developed to identify incident
      leukemia, lymphoma, lung, colorectal, stomach, and breast cancer. We identified a
      cohort of subjects aged >or=65 (1997-2000) from Pennsylvania Medicare and drug
      benefit program data linked with the state cancer registry. We calculated
      sensitivity, specificity, and positive predictive values of the claims-based
      definitions using registry as the gold standard. We further assessed the
      agreement between diagnosis dates from two data sources. RESULTS: All definitions
      had very high specificity (>or=98%), while sensitivity varied between 40% and
      90%. Test characteristics did not vary systematically by age groups. The date of
      first diagnosis according to Medicare data tended to be later than the date
      recorded in the registry data except for breast cancer. The differences in dates
      of first diagnosis were within 14 days for 75% to 88% of the cases. Bias due to
      outcome misclassification of our claims-based definition of cancer was minimal in
      our example of a cohort study. CONCLUSIONS: Claims data can identify incident
      hematologic malignancies and solid tumors with very high specificity with
      sufficient agreement in the date of first diagnosis. The impact of bias due to
      outcome misclassification and thus the usefulness of claims-based cancer
      definitions as cancer outcome markers in etiologic studies need to be assessed
      for each study setting.

PMID- 17447150
TI  - Erroneous mass transit system and its tended relationship with motor vehicular
      air pollution (An integrated approach for reduction of urban air pollution in
      Lahore).
AB  - Air pollution is threat to the lives of people living in big cities of Pakistan.
      In Lahore 1,250 people die annually because of air pollution. Mass transit system
      that can be put forth as solution to urban air pollution is contingent with right
      choice of system and its affiliation with motorized vehicles and nature of urban
      air pollution. Existing mass transit system in Lahore due to untrue operation
      causes surfeit discharge of motor vehicular carbon monoxide. Tended relationships
      of mass transit system with motorized vehicles and urban air pollution are quite
      noteworthy. The growing motor vehicles (a consequence of flawed public mass
      transit system) are potential source of urban air pollution. This paper attempts
      to highlight correlations and regression curves of existing mass transit system.
      Further it recommends a two facet approach for reduction of motor vehicular air
      pollution in Lahore.

PMID- 17447149
TI  - Epigenomic differentiation in mouse preimplantation nuclei of biparental,
      parthenote and cloned embryos.
AB  - Chromosomes, sub-chromosomal regions and genes are repositioned during cell
      differentiation to acquire a cell-type-specific spatial organization. The
      constraints that are responsible for this cell-type-specific spatial genome
      positioning are unknown. In this study we addressed the question of whether
      epigenetic genome modifications may represent constraints to the acquisition of a
      specific nuclear organization. The organization of kinetochores, pericentric
      heterochromatin and the nucleolus was analysed in pre-implantation mouse embryos
      obtained by in-vitro fertilization (IVF), parthenogenetic activation (P) and
      nuclear transfer (NT) of differentiated somatic nuclei, which possess different
      epigenomes. Each stage of pre-implantation embryonic development is characterized
      by a stage-specific spatial organization of nucleoli, kinetochores and
      pericentric heterochromatin. Despite differences in the frequencies and the time
      course of nuclear architecture reprogramming events, by the eight-cell stage P
      and NT embryos achieved the same distinct nuclear organization in the majority of
      embryos as observed for IVF embryos. At this stage the gametic or somatic nuclear
      architecture of IVF or P and NT embryos, respectively, is replaced by a common
      embryonic nuclear architecture. This finding suggests that the epigenome of the
      three types of embryos partially acts as a constraint of the nuclear organization
      of the three nuclear subcompartments analysed.

PMID- 17447151
TI  - Heavy metals in water, sediment and tissues of Liza saliens from Esmoriz-Paramos
      lagoon, Portugal.
AB  - Esmoriz-Paramos lagoon is an ecosystem of great ecological importance that is
      located on the northwest coast of Portugal and has been degraded as a result of
      industrial and anthropogenic activities. Concentrations of heavy metals (Cr, Cu,
      Pb and Zn) were measured in water, sediment and in tissues (liver and muscle) of
      Liza saliens, which is the dominant fish from the lagoon. Comparisons between
      metal concentrations in water and sediments were made with those in tissues of
      fish caught at the lagoon. Metals in water were quantified predominantly bound to
      particulate and equalled or exceeded the limit of chronic reference values. Metal
      concentrations in sediments varied among sampled sites. The relative order of
      concentrations was "Zn > Cu approximately Pb > Cr" the same pattern observed for
      metals in water. Metals in fish tissues showed higher concentrations in liver
      (262 mg CuxKg(-1) and 89 mg ZnxKg(-1)) than in muscle (<3 mg CuxKg(-1) and 26 mg
      ZnxKg(-1)), while Pb and Cr were not detected. These results suggest that Cu and
      Zn are the metals of major concern in the lagoon. Mullet detritivorous feeding
      habits, bioaccumulation pattern and the high sediment metals concentrations
      relative to the water suggest that sediments can be the most important source of
      contamination in this ecosystem. The positive relationship found between Cu in
      liver and fish length demonstrates that time of exposure is a crucial factor in
      bioaccumulation. Condition indices (K and HSI) in mullets from the lagoon were
      higher compared to mullets from sea, suggesting abnormal condition in the lagoon
      population. We conclude that metals chronic exposure in the lagoon can impose
      considerable fish stress. The results also show that the lagoon is an area of
      environmental concern.

PMID- 17447152
TI  - The 7th Transgenic Technology meeting: debut for "down under"
      (http://www.tasq.uq.edu.au/TT2007).
AB  - The 7th Transgenic Technology meeting was held in Brisbane, Australia on February
      12-14, 2007. Not only did this gathering mark a milestone as it was hosted
      outside the European continent for the first time, but also because it was the
      initial meeting to be held on behalf of the new International Society for
      Transgenic Technologies (ISTT, http://www.transtechsociety.org/ ). As in previous
      years, the topics were aimed towards both a scientific as well as a technical
      audience. The subjects covered a wide range of cutting edge applications in the
      field of genetic modifications in animal models, with the focus on (but by no
      means limited to) mice. True to the meetings tradition, a large emphasis was also
      laid on discussions about the management of transgenic production units. With the
      beautiful Australian sun shining over the venue, and a large number of
      exceptional speakers, this was a most pleasant and informative conference.

PMID- 17447153
TI  - Hyperkalemia associated to hepatitis in a peritoneal dialysis patient.
AB  - Hyperkalemia is an unusual complication in peritoneal dialysis patients, having a
      prevalence of around 0.8% among the continuous ambulatory peritoneal dialysis
      (CAPD) population. The main cause of hyperkalemia in this group is the release of
      potassium from sources such as gross haematomas and rhabdomyolysis. However,
      there is no previous report regarding hyperkalemia induced by intracellular
      potassium shift into the intravascular compartment secondary to drug-induced
      acute hepatitis in peritoneal dialysis. We present the following case report of a
      peritoneal dialysis patient, well dialyzed and on a low-potassium diet, who was
      admitted in our hospital with paralysis secondary to hyperkalemia (serum
      potassium: 7 mmol/l). Both disorders disappeared using continuous automated
      peritoneal dialysis (APD) until liver enzymes normalized. We concluded that acute
      hepatitis can be a cause of hyperkalemia in a properly nourished and well
      dialyzed peritoneal dialysis patient.

PMID- 17447154
TI  - Does cyclosporine achieve a real advantage for treatment of idiopathic nephrotic
      syndrome in children? A long-term efficacy and safety study.
AB  - BACKGROUND: Cyclosporine (CsA) was found to be efficient in decreasing
      proteinuria in both steroid-dependent and steroid-resistant nephrotic patients.
      We aimed to explore the potential long-term benefits and hazards of CsA and their
      predictors among a large group of nephrotic patients. METHODS: In this
      retrospective analysis, we included 197 pediatric patients with idiopathic
      nephrotic syndrome (INS) of whom 103 were steroid dependent and 94 steroid
      resistant. RESULTS: CsA induced complete remission in 132 (67%) and partial
      response in 13 (6.6%). Cyclosporine was received for a period of 22.16 +/- 12.21
      months. Univariate analysis showed that the response to CsA was significantly
      better in steroid-dependent children, in minimal change disease (MCD), diffuse
      mesangial proliferative glomerulonephritis (DMP) and focal segmental
      glomerulosclerosis (FSGS) than in other pathological lesions and in those who had
      lower quantities of pretreatment proteinuria. Only the prior response to steroids
      and concomitant use of ketoconazole with CsA were valid predictors for better
      response to CsA with multivariate analysis. Discontinuation of the drug in 40
      patients resulted in relapse in 26 patients while the remaining 14 patients
      maintained remission. Renal dysfunction developed in 18 patients of whom 12
      recovered completely on drug discontinuation. Thirty-seven patients developed
      hypertension. Multivariate analysis showed that all side-effects were
      significantly more prevalent in CsA-resistant patients. CONCLUSION: CsA is
      effective and well tolerated in the long-term treatment of INS in children,
      however two thirds of cases showed relapse after CsA discontinuation.

PMID- 17447155
TI  - Cloning and characterization of the human gene RAP2C, a novel member of Ras
      family, which activates transcriptional activities of SRE.
AB  - The Ras family regulates a wide variety of cellular functions that include cell
      growth, differentiation, and apoptosis. In this study, we identified a novel
      human gene named RAP2C, isolated from human testis cDNA library, and mapped to
      Xq26.2 by searching the UCSC genomic database. The RAP2C cDNA contains an open
      reading frame of 552 bp, encoding a putative protein of 183 amino acid residues.
      The predicted protein contains a RAS domain. By RT-PCR analysis in various
      tissues, RAP2C was found to be principally expressed in the liver, skeletal
      muscle, prostate, uterus, rectum, stomach, and bladder and to a less extent in
      brain, kidney, pancreas, and bone marrow. RAP2C protein was located in cytoplasm
      when overexpressed in COS-7 cells. Reporter gene assays showed that
      overexpression of RAP2C in HEK293T cells activated the transcriptional activities
      of serum response element (SRE). These results indicate that RAP2C is a novel
      member of the Ras family, belonging to the Rap branch of small GTPase proteins
      and may be involved in SRE-mediated gene transcription.

PMID- 17447156
TI  - Evaluation of tissue discards after implementation of anti-HBc test in a tissue
      bank in Spain.
AB  - The recent introduction as a minimum test required in The Guide to Safety and
      Quality Assurance for Organs, Tissues and Cells (Council Europe) and the
      Directive 2004/23/EC applied to donation, procurement, testing, processing,
      preservation, storage and distribution of human cells and tissues make necessary
      the implementation of these markers in all European Tissue Establishments. In
      this study we have analyzed the impact in tissues discard by introducing anti-HBc
      in a European Tissue Establishment in a country with a high prevalence of HBV
      infection. The adoption of this exclusion criteria in this region results in
      acceptably rejection rates among tissue donors, although some studies are needed
      on basis a risk assessment to determine the eligibility for clinical use.

PMID- 17447157
TI  - Enhanced gene transfer into brain capillary endothelial cells using Antp-modified
      DNA-loaded nanoparticles.
AB  - Brain capillary endothelial cells (BCECs) have been considered as one of the
      primary targets for cerebral gene therapy. However, the cells, well-known for
      their poor function of endocytosis, are difficult to be transfected by general
      non-viral vectors. The aim of this study was to enhance the efficiency of
      transfection and expression in BCECs of DNA/polymer nanoparticles with the
      modification of membrane-penetrating peptide, Antennapedia peptide (Antp)
      polyethylenimine (PEI) and polyamidoamine (PAMAM) were chosen to prepare Antp
      modified DNA-loaded nanoparticles with a complex coacervation technique. After a
      20-min transfection, the efficiency, in terms of transfection and expression, of
      DNA/PEI NP or DNA/PAMAM NP was enhanced significantly with the modification of
      Antp. After a 3-h transfection of DNA/Antp/PEI NP, there was no difference in
      cellular uptake but an enhancement in gene expression, compared to DNA/PEI NP
      alone. However, both the transfection and expression efficiency of DNA/PAMAM NP
      were enhanced using Antp. These observations suggest that Antp can increase the
      membrane-penetrating ability of DNA-loaded nanoparticles, which can be employed
      as novel non-viral gene vectors.

PMID- 17447158
TI  - Comparing the chemical spaces of metabolites and available chemicals: models of
      metabolite-likeness.
AB  - The chemical space covered by compounds involved in metabolic reactions was
      compared with that of a random dataset of purchasable compounds by
      chemoinformatics techniques. The comparison was based on 3D structure, 2D
      structure, or descriptors of global properties, by means of self-organizing maps,
      random forests, and classification trees. The overlap between metabolites and non
      metabolites was observed to be the least in the space defined by the global
      descriptors, the most discriminatory features being the number of OH groups,
      presence of aromatic systems, and molecular weight. Discrimination between the
      two datasets was achieved with accuracy up to 97%. Models were built to produce a
      metabolite-likeness parameter. A relationship between metabolite-likeness and
      ready biodegradability was observed.

PMID- 17447159
TI  - The effects of retinol on postprandial parameters in men with different FABP2
      promoter haplotypes.
AB  - The fatty acid binding protein 2 (FABP2) mediates the intestinal uptake of fatty
      acids. We and others have identified six FABP2 promoter polymorphisms which
      result in two haplotypes, A and B. Reporter-gene assays indicated different
      activity in FABP2 promoter alleles A and B and different responsiveness to PPAR
      ligands. IN SILICO analysis revealed different putative binding sites in FABP2
      haplotypes for retinoid-dependent transcription factors. Therefore, we assumed
      that retinol supplementation may effect postprandial fat uptake differently in
      men with FABP2 promoter haplotype A and B. To test this hypothesis, we
      administered 5000 I.U. retinol/day for 8 weeks to 19 homozygotes for AA and 21
      homozygotes for BB and assessed the alteration of postprandial triglycerides
      during this intervention. FABP2 genotype groups did not significantly differ in
      anthropometric and laboratory parameters. The alteration of postprandial
      triglycerides did not differ significantly between genotypes during intervention.
      This also held true after adjustment for BMI. Furthermore, in a subgroup which
      had a combination of promoter and common exon polymorphism, the alteration of the
      postprandial triglycerides did not differ between genotypes. In conclusion, the
      postprandial triglyceride metabolism of FABP2 promoter AA and BB did not respond
      differently to retinol administration even though IN SILICO analysis suggested
      this.

PMID- 17447160
TI  - Expression of chemokine receptors in insulin-resistant human skeletal muscle
      cells.
AB  - Adipokines including chemokines are able to induce insulin resistance in human
      skeletal muscle cells, which may also be relevant for the observed link between
      obesity and diabetes. This study is aimed to analyze the expression of chemokine
      CC motif receptors (CCRs) in the insulin-resistant state in human skeletal muscle
      cells. Differentiated skeletal muscle cells were incubated for 24-72 hours with
      high concentrations of glucose and insulin (GI) or TNFalpha. In addition,
      myocytes were co-stimulated with monocyte chemotactic protein (MCP)-1 or
      adipocyte-conditioned medium (CM) and TNFalpha for 24 and 48 hours. Treatment
      with GI rapidly induced insulin resistance whereas TNFalpha impaired insulin
      signaling in a more chronic fashion (48-72 h). CM and MCP-1 also induced insulin
      resistance that was, however, not increased by co-stimulation with TNFalpha.
      Expression of CCR2 was decreased during differentiation but up-regulated in
      insulin-resistant myocytes after treatment with GI (24-72 h) and TNFalpha (72 h).
      Expression of CCR4 and CCR10 was down-regulated after treatment with TNFalpha,
      MCP-1, and CM. Our data show that the expression of CCR2, CCR4, and CCR10 is
      differentially regulated by different insulin resistance-inducing treatments in
      myotubes. However, we could not find a clear correlation between the level of
      insulin resistance and CCR expression in myotubes. In conclusion, we propose that
      upregulation of CCR2 in skeletal muscle does not represent a major step leading
      to muscle insulin resistance.

PMID- 17447161
TI  - TNF-alpha alters visfatin and adiponectin levels in human fat.
AB  - Adiponectin and visfatin are newly discovered adipokines that are strongly
      expressed in human visceral adipose tissue. To identify new regulatory mechanisms
      in fat, the effect of TNF-alpha (TNF) on adiponectin, on its two receptors, and
      on visfatin was investigated by incubating human visceral adipose tissue from
      patients without diabetes mellitus with TNF for 24, 48 and 72 hours. The mRNA
      expression of visfatin, adiponectin, and its two receptors, as well as the
      protein expression of adiponectin were determined. A decrease of adiponectin mRNA
      expression of 97% after incubation with TNF (5.75 nmol/l) for 24 hours, a
      decrease of 91% after 48 hours, and a decrease of 96% after 72 hours were
      measured. The reduction of protein expression was measured to be 42% after 24
      hours, 28% after 48 hours, and 39% after 72 hours of incubation with TNF (5.75
      nmol/l). The mRNA level of adiponectin receptor 1 (AdipoR1) was elevated about
      72% after 48 hours of incubation and 67% after 72 hours of incubation, whereas
      the mRNA expression of adiponectin receptor 2 (AdipoR2) was not altered
      significantly. The visfatin mRNA level was found to be highly increased by 255%
      after 24 hours and 335% after 48 hours and 341% after 72 hours of incubation with
      TNF (5.75 nmol/l). Our results support the concept of visceral adipose tissue as
      an endocrine organ. We demonstrate that TNF has regulatory functions on
      adiponectin, AdipoR1 and on visfatin in human visceral adipose tissue. TNF levels
      are elevated in states of obesity and insulin resistance. Due to this fact TNF
      could be the reason that there is a decrease in the level of adiponectin, whereas
      there is an increase in the level of visfatin in states of obesity and insulin
      resistance.

PMID- 17447162
TI  - Effects of dietary equol on the pituitary of the ovariectomized rats.
AB  - The aim of our study was to evaluate the effects of dietary equol, metabolite of
      a phytoestrogen daidzein, on the secretion of prolactin (PRL) and lutenizing
      hormone (LH), as well as the expression of estrogen receptors (ERalpha, ERbeta
      and truncated estrogen receptor-1 (TERP-1) in the pituitary gland of
      ovariectomized (ovx) female Sprague-Dawley rats. Two doses of equol (50 mg/kg of
      chow and 400 mg/kg of chow) were used and the results were compared with the
      effects of estradiol 3-benzoate (E2B), also given at two doses (4.3 mg/kg of chow
      and 17.3 mg/kg of chow). Treatment period was 3 months. Dietary equol
      administration at the high dose increased significantly serum PRL levels. This
      effect was also observed in the E2B group but this difference did not reach
      statistical significance. Surprisingly, high dose dietary equol treatment also
      significantly increased serum LH levels, which was in contrast to E2B treatment
      where serum LH levels were significantly decreased at both doses. Serum LH levels
      in the equol low group were unaffected. Equol treatment had no effects on
      pituitary ERalpha or ERbeta gene expression. In contrast, high dose E2B treatment
      increased significantly pituitary ERalpha mRNA levels but decreased those of
      ERbeta. Both doses of E2B also increased significantly pituitary TERP-1 mRNA
      levels. This effect was also observed in the equol high group but at a much
      smaller magnitude. In conclusion, high dose dietary equol administration to ovx
      rats exerts estrogenic like effects on the lactotropes and anti-estrogenic on the
      gonadotropes.

PMID- 17447163
TI  - Difference of NPY and its receptor gene expressions between obesity and obesity
      resistant rats in response to high-fat diet.
AB  - AIM: To investigate the effect of high-fat diet on expressions of hypothalamic
      neuropeptide Y (NPY) and Y1, Y2, Y5 receptors and the mechanism relative to the
      susceptibility of obesity. METHODS: Thirty-six female SD rats were randomly
      divided into high-fat diet group (HF, n=27) and chow food group (CF, n=9), and
      given either HF or CF diet for 13 weeks. Then the HF diet group was subdivided
      into dietary induced obesi-ty (DIO) and dietary induced obesity resistant (DIO-R)
      rat according to the final body weight. Body weight, caloric intake, energy
      efficiency, visceral fat pads were measured and compared. The levels of plasma
      and hypothalamic NPY were determined by Radioimmunoassay. Real-time Polymerase
      Chain Reaction (PCR) was used to measure the gene expression of NPY and its
      receptors in hypothalamus. RESULTS: Body weight, caloric intake, energy
      efficiency and visceral fat pads in DIO rats were higher significantly than those
      in CF or DIO-R rats (p<0.01). No difference in plasma NPY level was detected
      among the three groups (p>0.05); the hypothalamic NPY level was significantly
      higher in DIO group than in CF or DIO-R group (p<0.01). Gene expression levels of
      NPY and Y1, Y2, Y5 receptors were higher significantly in DIO group than in CF or
      DIO-R group (p<0.01), while no significant difference was found between DIO-R and
      CF rats (p>0.05), except that Y2 receptor was lower in DIO-R rats (p<0.01).
      CONCLUSIONS: SD rat fed with a HF diet showed different susceptibility to
      obesity, and up-regulated hypothalamic NPY and Y1, Y2, Y5 receptor gene
      expressions were closely associated with being predisposed to obesity and
      overeating of DIO rats.

PMID- 17447164
TI  - Effect of anabolic steroid nandrolone decanoate on the properties of certain
      enzymes in the heart, liver, and muscle of rats, and their effect on rats'
      cardiac electrophysiology.
AB  - Nandrolone decanoate (ND) is an anabolic steroid, modified to enhance anabolic
      rather than androgenic actions. The physiological effects of ND treatment are
      often used in various aspects of medical practice. In this investigation we have
      tried to establish whether a single, high dose of ND (20 mg/kg) would cause any
      anabolic effects. Moreover, we have attempted to correlate the eventual effects
      with changes in the activity and kinetic properties of anabolic- and bioenergetic
      involved enzymes in different tissues of rats, along with the rats' ECG
      parameters. The body and liver weights of the rats were unchanged, but heart
      weight had increased 10 days after ND injection. Electrocardiographic data showed
      a small prolongation of the QRS complex 3, 6, and 10 days after ND treatment. It
      was established that ND causes activation of glucose-6-phosphate and 6
      phosphogluconate dehydrogenases, malic enzyme, and NADP-linked isocitrate
      dehydrogenase in rat hearts. Moreover, 6-phosphogluconate dehydrogenase from the
      hearts of ND-treated rats showed higher affinity to its substrate, in comparison
      with control. Activation of transketolase by ND in the liver was accompanied by
      inhibition of glucose-6-phosphate and 6-phosphogluconate dehydrogenases. We
      observed an increase of glucose 6-phosphate dehydrogenase and NAD-linked malate
      dehydrogenase in the muscle of ND treated rats. It may be concluded that ND in a
      single high dose exhibits cardiotrophic action, especially towards the increase
      of heart dehydrogenases activity which generates NADPH and supplies ribose
      phosphate for the biosynthesis of nucleotides and nucleic acids. On the other
      hand, ND may cause activation of ATP synthesis in muscle by enhanced malate
      aspartate shuttle action.

PMID- 17447166
TI  - Different uptake and handling of oleoyl-estrone by fetuses and neonatal rats.
AB  - To determine whether oleoyl-estrone can be transferred from mothers to their
      offspring either during pregnancy or lactation, a gavage of tracer dose of (3)H
      Oleoyl-estrone was given to 21-day pregnant rats and to lactating rats on day 15
      after delivery. In pregnant rats, the label was found in maternal blood as well
      as in liver and fetal serum, the latter showing the highest specific activity
      observed. In lactating rats, oleoyl-estrone label was found both in the mammary
      gland and maternal serum; in the pups, label was found in their stomach contents
      (i.e., clotted milk) and serum. The results suggest that the placenta effectively
      blocks the passage of oleoyl-estrone to the fetuses probably because of its high
      esterase activity. On the other hand, oleoyl-estrone is easily transferred from
      dams to pups, as a component of milk.

PMID- 17447165
TI  - Rapid inhibitory effect of corticosterone on histamine release from rat
      peritoneal mast cells.
AB  - Glucocorticoids are steroids endowed with powerful anti-inflammatory properties,
      which are routinely believed to require several hours to take effect through
      modulation of gene expression. Our recent report has shown that glucocorticoids
      could inhibit allergic reaction within 10 minutes, which the classical genomic
      mechanism could not explain. Histamine is thought to be one of major mediators in
      the allergic reaction, and IgE-mediated histamine release from mast cells plays a
      pivotal role in allergic diseases. Here, we have determined a rapid effect of
      corticosterone on histamine release from rat peritoneal mast cells, using
      fluorometric assay. The results showed that corticosterone could inhibit antigen
      induced histamine release from rat peritoneal cells within 15 minutes (p<0.05),
      which could be mimicked by membrane-impermeable BSA conjugated corticosterone
      (p<0.05). Neither glucocorticoid nuclear receptor antagonist nor protein
      synthesis inhibitor could block the rapid action (p<0.05). The study provided
      evidence that nongenomic mechanism might be involved in rapid effect of
      glucocorticoids on mast cells in allergic disease.

PMID- 17447167
TI  - The influence of preadipocyte differentiation capacity on lipolysis in human
      mature adipocytes.
AB  - The ability of catecholamines to maximally stimulate adipocyte lipolysis
      (lipolytic capacity) is decreased in obesity. It is not known whether the
      lipolytic capacity is determined by the ability of adipocytes to differentiate.
      The aim of the study was to investigate if lipolytic capacity is related to
      preadipocyte differentiation and if the latter can predict lipolysis in mature
      adipocytes. IN VITRO experiments were performed on differentiating preadipocytes
      and isolated mature adipocytes from human subcutaneous adipose tissue. In
      preadipocytes, noradrenaline-induced lipolysis increased significantly until
      terminal differentiation (day 12). However, changes in the expression of genes
      involved in lipolysis (hormone sensitive lipase, adipocyte triglyceride lipase,
      the alpha2-and beta1-adrenoceptors, perilipin, and fatty acid binding protein)
      reached a plateau much earlier during differentiation (day 8). A significant
      positive correlation between lipolysis in differentiated preadipocytes and mature
      adipocytes was observed for noradrenaline (r=0.5, p<0.01). The late
      differentiation capacity of preadipocytes measured as glycerol-3-phosphate
      dehydrogenase activity was positively correlated with noradrenaline-induced
      lipolysis in preadipocytes (r=0.51, p<0.005) and mature fat cells (r=0.35,
      p<0.05). In conclusion, intrinsic properties related to terminal differentiation
      determine the ability of catecholamines to maximally stimulate lipolysis in fat
      cells. The inability to undergo full differentiation might in part explain the
      low lipolytic capacity of fat cells among the obese.

PMID- 17447168
TI  - Sex hormone-binding globulin selectively modulates estradiol-regulated genes in
      MCF-7 cells.
AB  - Human sex hormone-binding globulin inhibits the effects of estradiol on
      proliferation and apoptosis of breast cancer cells. We report here the effect of
      sex hormone-binding globulin on estradiol regulation of gene expression in MCF-7
      breast cancer cells using a selected set of genes. Estradiol upregulates genes
      that are positive regulators of proliferation (e.g., bcl-2, c-fos, c-myc, cyclin
      D) or/and related to more aggressive form of breast cancer (e.g. BRCA-1, EGF-R)
      and downregulates two genes (c-jun and ERalpha). Sex hormone-binding globulin
      modulates only a selected group of estradiol-controlled genes (inhibiting
      upregulation of bcl-2, c-myc, EGF-R, PR, and downregulation of ERalpha), starting
      48 hours after treatment. Our study demonstrates that in breast cancer cells, sex
      hormone-binding globulin is effective on few selected genes which are involved in
      cell growth and apoptosis or related to cell estrogen-dependence and that the
      protein regulation of estradiol effect is selected and specific. Sex hormone
      binding globulin action in estrogen breast cancer cells is strongly associated to
      cell growth and estrogen-sensitivity.

PMID- 17447169
TI  - Accelerated clearance of plasma triglycerides and free fatty acids in omega3
      depleted rats.
AB  - The present study aims mainly at exploring the effects of a severe depletion in
      polyunsaturated long-chain omega3 fatty acids upon the fate of circulating
      lipids. The plasma concentration and fatty acid pattern of triglycerides,
      diglycerides, free fatty acids, and phospholipids were measured in omega3
      depleted and control rats injected intravenously one hour before sacrifice with
      either saline, a control medium-chain triglyceride:olive oil emulsion or a medium
      chain triglyceride:fish oil emulsion recently found to rapidly increase the
      phospholipid content of C20:5omega3 and C22:6omega3 in different cell types. The
      estimated fractional removal rate of the injected triglycerides and the clearance
      of free fatty acids from circulation were both higher in omega3-depleted rats
      than in control animals. The injection of the lipid emulsions apparently
      inhibited intracellular lipolysis, this being least pronounced in omega3-depleted
      rats. The increased clearance of circulating triglycerides and unesterified fatty
      acids in omega3-depleted rats may favor the cellular accumulation of lipids. In
      turn, such an accumulation and the lesser regulatory inhibition of tissular
      lipolysis may match the increased clearance of circulating unesterified fatty
      acids and, hence, account for the lack of any significant difference in plasma
      unesterified fatty acid concentration between these and control animals.

PMID- 17447170
TI  - Promoter polymorphisms of UCP1, UCP2, and UCP3 are not associated with diabetic
      microvascular complications in type 2 diabetes.

PMID- 17447171
TI  - Elevation of salivary melatonin levels by viewing a humorous film in patients
      with atopic eczema.

PMID- 17447172
TI  - Clinical and social determinants of antipsychotic polypharmacy for Chinese
      patients with schizophrenia.
AB  - Most prescription pattern surveys have found a high rate of antipsychotic
      polypharmacy. To date few studies have investigated antipsychotic polypharmacy in
      Chinese patients with schizophrenia in general and outpatients in particular.
      This study examined the frequency and sociodemographic and clinical correlates of
      antipsychotic polypharmacy in Hong Kong (HK) and Beijing (BJ), China. Three
      hundred and ninety-eight clinically stable outpatients with schizophrenia were
      randomly selected and interviewed in HK and BJ using standardized assessment
      instruments. Antipsychotic polypharmacy was found in 17.6% ( N=70) of the whole
      sample and in 28% and 7.1% of the HK and BJ samples, respectively. Polypharmacy
      was associated with monthly income, severity of negative symptoms and
      extrapyramidal side effects (EPS), use of depot antipsychotic and anticholinergic
      drugs, doses of antipsychotics, and the number of hospitalizations. In multiple
      logistic regression analysis, younger age, number of hospitalizations, site (HK
      vs. BJ), and the use of depot antipsychotics were all significantly associated
      with antipsychotic polypharmacy. Although the ethnic and clinical characteristics
      of the two cohorts were nearly identical, there was a wide variation in the
      prescription frequency of antipsychotic polypharmacy between HK and BJ,
      suggesting that sociocultural and economical factors and traditions of
      psychiatric practice all played a role in determining antipsychotic polypharmacy.
      Clinicians should bear in mind that, at least for clinically stable patients, no
      scientifically sound therapeutic principles for antipsychotic polypharmacy exist.

PMID- 17447173
TI  - Escitalopram in clinical practice: results of an open-label trial in outpatients
      with depression in a naturalistic setting in Germany.
AB  - INTRODUCTION: An open, multi-center, study was designed to address the efficacy
      and tolerability profile of treatment with escitalopram under naturalistic
      conditions in outpatients with depression. METHODS: A total of 11,760 patients
      were treated with escitalopram and followed for 8 weeks. Rating scales included
      the Clinical Global Impression-Severity (CGI-S), the Clinical Global Impression
      Improvement (CGI-I), and a short version of the Montgomery-Asberg Depression
      Rating Scale (svMADRS) for assessment of various clinical parameters. RESULTS:
      During the course of the study, patients showed a clear pattern of improvement in
      their general state of health (CGI-S) and a decrease in the severity of their
      depression. The majority (82.8%) of patients initially received 10 mg/day
      escitalopram. By the end of the trial period, 32.5% of the patients were treated
      with 20 mg/day escitalopram compared to 64.0% receiving 10 mg/day escitalopram.
      After 2 weeks, 40.7% of patients were much or very much improved (CGI-I < or =2),
      increasing to 82.5% at the last assessment. There were no significant differences
      in response to treatment between women and men, with regard to treatment by
      specialists versus GPs, or with regard to age (< or =65 versus >65 years of age).
      Adverse reactions were similar to those found in controlled trials, and no new
      reactions were noted. The most common adverse reactions were nausea, anxiety, and
      vertigo. CONCLUSIONS: This observational study corroborates the high therapeutic
      efficacy of escitalopram treatment, while confirming the tolerability profile, in
      a naturalistic treatment setting.

PMID- 17447174
TI  - Sexual impairment in psychiatric inpatients: focus on depression.
AB  - INTRODUCTION: Although sexual side effects are a common reason for noncompliance
      with medication, information on impairment of sexuality in psychiatric inpatients
      is scarce. METHODS: In the present multi-center study, data on several aspects of
      sexual functioning were collected in psychiatric inpatients using a previously
      validated questionnaire. RESULTS: A high overall prevalence of sexual dysfunction
      was reported by participants and was highest in depressed subjects. Patients
      receiving antidepressants suffered from more frequent and more severe impairment
      of sexuality than did subjects receiving neither antidepressants nor
      antipsychotics or opioids. DISCUSSION: Judging from this data, sexual impairment
      appears to be a frequent and underestimated problem in psychiatric inpatients
      with a high prevalence across all diagnostic groups, particularly in depressed
      subjects. Female patients attribute this impairment mainly to their mental
      illness, whereas male patients tend to assign their impairments primarily to
      their medication.

PMID- 17447175
TI  - Regional cerebral glutamate concentrations and chronic tobacco consumption.
AB  - INTRODUCTION: Increasing evidence indicates a crucial role of glutamate in the
      brain reward system and nicotine addiction. Because the pertinent models involve
      frontal and hippocampal glutamatergic projections, our goal was to investigate
      cerebral glutamate concentrations in healthy subjects with different smoking
      behavior. METHODS: Glutamate was measured with proton magnetic resonance
      spectroscopy at 3 tesla in the left hippocampus and anterior cingulate cortex
      (ACC) in 13 chronic tobacco smokers, 9 former smokers, and 16 never-smokers using
      a dedicated quantification method. RESULTS: Glutamate concentrations did not
      differ between groups in either voxel ( F=1.151, DF=2, P=0.340). No significant
      correlations between glutamate concentrations and age of smoking onset, daily
      cigarette consumption, or lifetime exposure to tobacco smoke (pack-years) were
      observed. CONCLUSION: Our findings do not support a crucial role of cingulate or
      hippocampal glutamate concentration in chronic tobacco consumption. Besides group
      differences potentially gone unnoticed due to the limited sample size, however,
      these results cannot rule out dysfunctional glutamatergic neurotransmission or
      glutamate dysfunctions in other brain regions of smokers.

PMID- 17447176
TI  - Pregabalin augmentation of quetiapine therapy in the treatment of fibromyalgia:
      an open-label, prospective trial.
AB  - INTRODUCTION: Quetiapine has been shown to improve fibromyalgia symptoms,
      especially sleep disturbance, fatigue, morning stiffness, and mental well-being,
      but lacks an effect on pain. The purpose of this study was to evaluate if
      pregabalin, which has shown antialgic activity in fibromyalgia, added to
      quetiapine treatment additionally improved fibromyalgia symptomatology. METHODS:
      This was an open-label, 12-week study. Pregabalin was administered to 19 female
      fibromyalgia patients at a starting dose of 75 mg/day subsequently adjusted in
      according to the drug's efficacy and tolerability. Outcome measures included the
      Fibromyalgia Impact Questionnaire (FIQ), the Pittsburgh Sleep Quality Index, the
      Beck Depression Inventory, the State and Trait Anxiety Inventory, and the SF-12
      Health Survey. RESULTS: Data analysis was done on the Intention-To-Treat sample
      which included 18 patients. Pregabalin significantly improved the pain and
      tiredness after awakening subscales of the FIQ as well as the physical component
      of the SF-12. Six patients withdrew from the study, 3 because of side effects.
      CONCLUSIONS: Our results suggest that the use of pregabalin can be a useful
      augmentation strategy in fibromyalgia patients partially responding to
      quetiapine.

PMID- 17447177
TI  - Therapeutic drug monitoring of quetiapine in adolescents with psychotic
      disorders.
AB  - INTRODUCTION: There are developmental and age-dependent differences in the
      pharmacokinetics and the pharmacodynamics of drugs in children and adolescents.
      Therefore, there is a need to carry out standardised studies to find out
      therapeutic ranges of plasma/serum concentrations in psychopharmacotherapy of
      children and adolescents. The aim of this prospective study was to examine the
      relationship between quetiapine serum concentration, treatment response, and side
      effects in a clinical setting to elucidate the age-specific therapeutic range of
      quetiapine in adolescents. METHODS: Over a period of two years, therapeutic drug
      monitoring (TDM) was routinely performed in 21 adolescents (mean age was 15.9+/
      1.5 years, 57% male) with psychotic disorders according to the guidelines of the
      AGNP TDM expert group. The psychopathology was assessed by using the Clinical
      Global Impression Scale (CGI) and the Brief Psychiatric Rating Scale (BPRS). Side
      effects were assessed by using the Dose Record and Treatment Emergent Symptom
      Scale (DOTES). Trough quetiapine concentrations were determined under steady
      state conditions after multiple-dose regimes (median 600 mg/day; range 100-800
      mg/day). RESULTS: There was a marked variability of the serum concentrations,
      ranging from 19-877 ng/ml. 40.8% of the determined values were below and 24.5%
      above the therapeutic range (70-170 ng/ml) recommended for adults. None of the
      patients had severe side effects. We found a weak correlation between dose and
      serum concentration of quetiapine and no relationship between serum concentration
      and treatment response. DISCUSSION: There are several limitations of this study,
      and our results should therefore be interpreted with caution. Notwithstanding,
      differences in the ontogenesis of pharmacokinetics and pharmacodynamics may be
      the reason for the difference in the relationship between blood concentrations
      and therapeutic response to psychopharmaca in children, adolescents and adults.
      Further studies using larger samples, baseline assessment of psychopathology,
      definition of the treatment interval and investigation of clinically relevant
      interactions with various co-medications are warranted to improve the limitations
      of this pilot study.

PMID- 17447178
TI  - A randomized controlled clinical trial comparing "guideline exposed" and
      "guideline naive" physicians in respect to dosage selection and treatment outcome
      with doxepin in depressive disorders.
AB  - INTRODUCTION: Can prescribing of insufficient dosages and outcome of treatment
      with antidepressants in routine care be improved by guidelines? METHODS: 161
      general practitioners and 162 psychiatrists in private practice documented 1319
      patients, receiving doxepin for individual clinical reasons. Physicians were
      randomly divided into a guideline exposed and a control group. All physicians
      treated their patients according to individual clinical considerations. RESULTS:
      Average maximum daily dosage was 83 mg/d in the control and 95 mg/d in the
      intervention group (F=19.15; p<0). Only 3% of patients in both groups got the
      recommended dosage of 150 mg/d. Guideline exposure resulted in increased dosages
      preferably for milder forms of depression and in comparatively lower rates of
      improvement. CONCLUSION: Guideline exposure did not reach its goal in respect to
      the recommended dosage. It missed its goal in respect to improvement of outcome
      and even showed negative effects. Guidelines should be evidence-based not only by
      referring to literature reviews but by testing their clinical effects in
      controlled clinical trials.

PMID- 17447179
TI  - Cessation of complex visual hallucinations during treatment with mirtazapine.

PMID- 17447180
TI  - Extrapyramidal side effects associated with aripiprazole administration in a
      schizophrenic patient.

PMID- 17447181
TI  - Successful treatment of severe antidepressant-induced nausea with a combination
      of milnacipran and olanzapine.

PMID- 17447182
TI  - Rebound of weight gain following topiramate cessation.

PMID- 17447183
TI  - Bipolar switching after carbamazepine withdrawal.

PMID- 17447184
TI  - Obsessive-compulsive disorders due to neuroacanthocytosis treated with
      citalopram.

PMID- 17447185
TI  - The safety of prolonged indomethacin therapy.
AB  - The purpose of this study was to describe the fetal and newborn safety profile of
      prolonged indomethacin treatment during pregnancy. A retrospective cohort of 124
      pregnant women treated with indomethacin was used to assess the outcomes of
      oligohydramnios, constriction of the ductus arteriosus, and composite neonatal
      morbidity. Eight patients (6.5%) developed ductal constriction and nine patients
      (7.3%) developed oligohydramnios. Composite morbidity occurred in 36 neonates
      (29%). Ductal constriction, oligohydramnios, and composite morbidity were not
      associated with duration of therapy, gestational age at start or stop of therapy,
      time between dosing and delivery, or dose regimen. Prolonged indomethacin therapy
      rarely is associated with ductal constriction and oligohydramnios.

PMID- 17447186
TI  - Magnetic resonance imaging of the chest, abdomen, and pelvis in the evaluation of
      pregnant patients with neoplasms.
AB  - This article illustrates the magnetic resonance (MR) technique and MR imaging
      (MRI) findings of various neoplasms in chest, abdomen, and pelvis in pregnant
      patients. MRI can provide useful information about characterization and staging
      of maternal neoplasms without exposing the fetus to ionizing radiation and can be
      considered as a first-line cross sectional imaging method as an adjunct to
      ultrasonography.

PMID- 17447187
TI  - Relationship between thymulin and growth hormone secretion in healthy human
      neonates.
AB  - The relationship among circulating values of growth hormone (GH), thymulin, and
      zinc in 19 healthy human neonates at birth and at the 4th month of age, and in
      their respective mothers, was investigated. Cytofluorimetric analysis on some CD
      antigen markers was conducted on cord blood and peripheral blood mononuclear
      cells. Active thymulin and zinc plasma levels increased in newborns in comparison
      with their mothers. In neonates serum GH levels increased with a significant
      decline later. The expression of CD molecules from newborns at birth and from
      infants at the 4th month of age was inversely correlated with active thymulin,
      zinc, and GH levels, whereas CD4 antigen marker was positively correlated with
      the same parameters at the 4th month of life. A novel interrelationship among
      active thymulin, zinc, and GH exists from the early up to the late phase of
      newborn life, in which maternal zinc, via lactation, may be involved.

PMID- 17447188
TI  - Late postpartum eclampsia: report of two cases managed by uterine curettage and
      review of the literature.
AB  - The purpose of this study was describe two patients with rapid recovery of
      refractory late postpartum eclampsia (LPPE) following uterine curettage, and to
      evaluate the literature about supportive evidence for such a management in LPPE.
      A detailed literature search was performed focusing on studies reporting the
      clinical presentation, laboratory workup, imaging, and management of LPPE. Mean
      reported onset of LPPE was on postpartum day 7.0 +/- 2.9. Only 35.3% had a
      history of preeclampsia: these had earlier onset of seizures compared with the
      subjects without history of preeclampsia (4.3 +/- 1.4 versus 7.6 +/- 2.9 days; p
      < 0.005). Onset of seizure was correlated with systolic blood pressure (Pearson's
      r = 0.34; p < 0.05). Major associated symptoms were headaches (71.4%), visual
      changes (46.0%), and nausea/vomiting (22.2%); 67.5% of patients were proteinuric.
      The remaining laboratory tests were usually normal. Among the patients with a
      normal head computed tomography, magnetic resonance imaging identified additional
      abnormalities in 53.8% (seven of 13). A total of 69.7% of patients developed
      multiple seizure episodes, some of these occurred while the patient was receiving
      magnesium sulfate treatment; 82.5% of patients underwent magnesium therapy and
      approximately half of those patients required multiple antiseizure drugs. The
      number of seizures was only correlated with the diastolic blood pressure
      (Pearson's r = 0.52; p < 0.01). Even remote from delivery, headaches, visual
      change, and nausea/vomiting are important symptoms of LPPE. Hypertension and/or
      proteinuria are important diagnostic findings. LPPE is often characterized by
      refractory seizures and controlling the diastolic blood pressure is important.
      Patients presented in our case report showed no seizures after uterine curettage.
      This potential useful management for LPPE requires additional investigation.

PMID- 17447189
TI  - Hepatitis C in pregnancy.
AB  - Hepatitis C is the most common cause of chronic liver disease and liver
      transplantation, with 25,000 cases reported in the United States per year. By
      blood product screening, transfusion-related viral transmission has been
      virtually eliminated, and maternal fetal transmission is now one of the most
      important modes of transmission. Hepatitis C virus (HCV) infection is blood borne
      but only 25% of the infected pregnant women indicate a history of blood products
      transfusion or intravenous drug use. HCV transmission is 2- to 4-fold higher in
      women coinfected with HIV. Although cesarean delivery has not been shown to
      decrease perinatal transmission, it may have benefits in women with viremia at
      the time of delivery. During pregnancy, treatment of HCV is contraindicated, even
      though perinatal transmission is associated with a higher incidence of chronic
      liver disease. This review gives an update on the disease agent, risk factors,
      modes of transmission, diagnosis, treatment modalities, and perinatal issues that
      require further evaluation.

PMID- 17447190
TI  - Predictors and outcomes for pregnant women with vaginal-rectal carriage of
      community-associated methicillin-resistant Staphylococcus aureus.
AB  - The purpose of this study was to determine the predictors and outcomes of
      pregnant women with vaginal-rectal carriage of community-associated methicillin
      resistant Staphylococcus aureus (CA-MRSA). We performed an unmatched 1:4 case
      control study with two control groups (13 CA-MRSA cases, 52 methicillin-sensitive
      S. aureus (MSSA) controls, and 52 S. aureus-negative controls) via a
      retrospective medical record review. We found that CA-MRSA cases were 12.5 times
      significantly less likely to be colonized with group B streptococci (GBS)
      compared with MSSA controls in multivariable analyses. When we compared MSSA
      patients with S. aureus-negative patients, we found that MSSA patients were 4.5
      times significantly more likely to be colonized with GBS and 11 times
      significantly more likely to have a postpartum fever > or = 100.4 degrees F in
      multivariable analyses. Traditional risk factors for hospital-associated MRSA do
      not appear to predict vaginal-rectal CA-MRSA carriage in pregnant women. Instead,
      CA-MRSA carriage is significantly associated with lack of GBS carriage.
      Additional microbiologic studies and epidemiologic studies are needed to clarify
      the relationship between S. aureus and GBS, given that these two colonizing
      organisms have the potential to become pathogens.

PMID- 17447191
TI  - Intrauterine growth restriction and oligohydramnios among high-risk patients.
AB  - The purposes of this study were (1) to determine the prevalence of
      oligohydramnios (amniotic fluid index < 5.0 cm) among fetuses with intrauterine
      growth restriction (IUGR) and newborns identified as small for gestational age
      (SGA), and (2) among fetuses with IUGR, to determine the predictive accuracy of
      amniotic fluid index (AFI) < or = versus > 5.0 cm for adverse peripartum
      outcomes. This was a retrospective review of high-risk pregnancy that had
      reliable gestational age (GA) and needed weekly biophysical profile (BPP). Along
      with 95% confidence intervals (CIs), we calculated the likelihood ratios (LRs)
      and used guidelines promulgated by Evidence-Based Medicine Working Group. Among
      the 1859 singletons undergoing BPP, IUGR (estimated fetal weight < 10% for GA)
      was suspected in 22% (n = 410) and the prevalence of oligohydramnios was 6% (95%
      CI, 4 to 8%). SGA (birthweight < or = 10%) occurred among 28% (n = 517) of
      newborns and oligohydramnios was noted in 6% (95% CI, 4 to 8%). Among fetuses
      with IUGR, the LR of oligohydramnios to predict cesarean delivery for
      nonreassuring fetal heart tracing was 2.0 (range, 0.8 to 5.0); for newborns small
      for gestational age, 1.9 (range, 1.2 to 3.1), and for neonatal intensive care
      unit admission, 1.4 (range, 0.6 to 2.3) More than 90% of patients with IUGR or
      SGA have AFI > 5.0 cm, and oligohydramnios with IUGR is a poor predictor of
      peripartum complications.

PMID- 17447192
TI  - A case of prosthesis-patient mismatch complicating pregnancy.
AB  - Prosthesis-patient mismatch occurs when the effective prosthetic valve area is
      smaller than that of a normal human valve. Its importance in pregnancy is
      unknown. We describe an asymptomatic patient with higher than normal
      transvalvular gradients due to prosthesis-patient mismatch who developed
      congestive heart failure in late pregnancy. Our recommendation is that pregnant
      patients, particularly those with a small valve prosthesis, undergo serial
      echocardiography because these patients are at high risk of developing heart
      failure.

PMID- 17447193
TI  - Dexamethasone therapy interferes with the development of the neutrophil oxidative
      burst in vitro in very low birthweight infants.
AB  - Dexamethasone therapy is used in the treatment of chronic lung disease in very
      low birthweight (VLBW) neonates. However, several significant side effects have
      been observed in these patients, including an increased incidence of infection.
      We initiated a pilot study to examine the in vitro function of neutrophils from
      dexamethasone-treated VLBW infants. Following a 1-week course of dexamethasone,
      VLBW infants failed to demonstrate the increased oxidative burst that was
      observed in the age- and weight-matched untreated infants. These observations
      support recent evidence raising concern about effects on other organs when using
      dexamethasone in mechanically ventilated infants. In this example, impaired
      oxidative burst may be among the cellular factors contributing to the increased
      risk of infection during corticosteroid use in VLBW neonates in the neonatal
      intensive care setting.

PMID- 17447194
TI  - ["Good advice is precious." The second opinion from the point of view of an
      interdisciplinary cancer therapy center].
AB  - BACKGROUND AND OBJECTIVE: The setting up of an interdisciplinary tumor treatment
      center together with a "tumor board" has resulted in early specialty-bridging
      assessment and therapeutic decisions of cancers, some of them complex, in
      hospitalized patients with visceral tumors. It was the aim of this study to
      compare the use and value of the decisions of the tumor board ("second opinion")
      with those of the original assessment made elsewhere after primary surgical
      treatment. PATIENTS AND METHODS: Information on the tumor board's database,
      recorded explicitly as "external comments" or "second opinion" were accessed. The
      data were then classified according to organs or organ systems and further
      divided into those cases in which the primary tumor had not been treated, those
      with tumor recurrence and those with metastases or recurrence of metastases.
      RESULTS: 8298 cases were evaluated during a five-year period. There were 373
      "second opinions" (4.5%), most of the referrals relating to tumors of the upper
      gastrointestinal tract, corresponding to the focus of our institution. Previously
      untreated primary tumors amounted to 53.6% of cases, local recurrences in 14.7%
      and initial evidence of metastases of a visceral tumor in 9.9%. In 21.7%
      progression of a known metastasizing tumor was the main reason for requesting a
      second opinion. The second opinion agreed with the external decision for surgery
      alone in 16.4% of all enquiries. Minor modifications of the external therapeutic
      decisions were recommended in 5.9% of referred cases, while in 47.2% major
      changes were recommended. 28,7% of enquiries could not be evaluated because
      essential data were not available. CONCLUSIONS: Requests for a second opinion in
      the treatment of visceral tumors are still rare in Germany. Good and current
      findings are requisites for giving a reliable second opinion. In fewer than a
      fifth of cases was there agreement with regard to a primarily surgical
      intervention. The concept of multimodal forms of treatment are usually given
      priority, which underlines the need for establishing interdisciplinary advisory
      panels.

PMID- 17447195
TI  - [What is your diagnosis? Prolonged pericardial calcification/massive
      kyphoscoliosis/compressed lungs with atelectases suspected in the right
      segments].

PMID- 17447196
TI  - [Heterotaxia syndrome without congenital cardiac defects in dilated
      cardiomyopathy].
AB  - HISTORY AND OUTPATIENT INVESTIGATION: A 61-year-old woman presented with a six
      month history of chest pain and shortness of breath on normal activity. The past
      medical history included hypertension treated with ACE inhibitors. While still an
      outpatient a diagnosis was made of cardiomyopathy with left atrial and
      ventricular dilatation, systolic and diastolic heart failure, moderate mitral
      valve regurgitation and newly documented atrial fibrillation. INVESTIGATION:
      Right heart catheterization was carried out via the right femoral vein. The
      inferior vena cava was found to be on the left, none on the right. Venous inflow
      was via a dilated hemiazygos vein, a persistent left superior vena cava and a
      markedly dilated coronary sinus into the right atrium. The hepatic veins were
      also directly connected to the right atrium, as was shown by retrograde perfusion
      during a venogram. Coronary heart disease was excluded by angiography, but a
      right heart catheterization was not possible because of the atypical venous
      connections. Ultrasound examination revealed abdominal situs inversus and
      polysplenia. Magnetic resonance imaging of the thorax demonstrated bilateral
      bilobar lungs and bilateral hyparterial bronchi. DIAGNOSIS, TREATMENT AND COURSE:
      Heterotaxia with anomalous systemic veins and visceral defects was revealed
      during a diagnostic work-up, which was indicated by the finding of a dilated
      cardiomyopathy with chronic atrial fibrillation, moderate mitral valve
      regurgitation and arterial hypertension. Arterial hypertension and heart failure
      were successfully treated by medication. Attempts at rhythm control were
      unsuccessful. Safety measures were established to prevent thromboembolic
      complications and endocarditis. CONCLUSION: Congenital anomalies of the systemic
      veins in adults are often discovered incidentally, because they are usually
      asymptomatic. They may cause diagnostic and therapeutic difficulties in
      cardiology, phlebology and surgery. These anomalies may increase the risk of
      thrombotic and thrombembolic events. Together with polysplenia and situs inversus
      they are phenotypical components of heterotaxia. They may have various clinical
      consequences and may occur spontaneously or may be familial.

PMID- 17447197
TI  - [Radiotherapy and its consequences: a plea for an interdisciplinary dialogue].

PMID- 17447198
TI  - [Plastic surgery reconstruction of radiation injuries to the extremities].

PMID- 17447199
TI  - [Plastic surgery reconstruction of radiation-induced trunk and body cavity
      defects].

PMID- 17447200
TI  - [Plastic surgical procedures in radiation sequelae of neck, breast and thoracic
      wall].

PMID- 17447201
TI  - Natural compounds as inhibitors of human neutrophil elastase.
AB  - The imbalance between human neutrophil elastase (HNE) and endogenous serine
      proteinase inhibitors is considered to cause a variety of HNE-mediated
      inflammatory disorders. Thus, HNE has been the object of intensive research to
      find potent inhibitors that target its destructive and pro-inflammatory action.
      This review focuses on natural compounds which have been demonstrated to inhibit
      the enzyme itself or its release from neutrophils. Some of the natural compounds
      discussed here may serve as lead structures suitable to be used for the
      development of semi-synthetic inhibitors, but up to now none has been found
      active enough to be directly used in therapy.

PMID- 17447204
TI  - Receptor mechanisms mediating non-genomic actions of sex steroids.
AB  - Sex steroid hormones, including estrogen, progesterone, and androgen, mediate
      their biological effects on cell proliferation, differentiation, and homeostasis
      through their respective nuclear receptors. In addition to functioning as ligand
      activated nuclear transcription factors to regulate gene transcription, these
      receptors also have been shown to mediate rapid activation of non-genomic
      signaling pathways independent of their transcriptional activity. Despite the
      fact that non-genomic effects of sex steroids have been observed since more than
      three decades ago, the receptor mechanisms mediating these rapid effects still
      are not well understood. A subpopulation of nuclear steroid receptors localized
      to the cell membrane or cytoplasm has been proposed to mediate steroid hormone
      activation of signaling pathways; however, novel membrane receptors unrelated to
      nuclear receptors have also been implicated. This review focuses on recent
      advances in our understanding of the nature of the receptors and mechanisms
      responsible for rapid non-genomic signaling actions of sex steroids, including
      novel membrane receptors and interactions of nuclear steroid receptors with
      membrane and cytoplasmic signaling molecules such as adapter proteins, G
      proteins, ion channels, and protein kinases. A better definition of receptor
      mechanisms involved in mediating activation of non-genomic signaling pathways is
      important to our overall understanding of the biology of steroid hormones.

PMID- 17447205
TI  - Actions of steroids in mitochondria.
AB  - Investigations of indirect and direct actions of steroids on the mitochondria are
      relatively new areas of research. In this review we provide brief background
      information regarding mitochondrial structure and function and then focus upon
      interactions of glucocorticoid, estrogen, androgen, and progesterone receptors
      with mitochondria. We evaluate the current evidence for steroid receptor
      localization in the mitochondria based on techniques of Western blot analysis,
      immunocytochemistry, electron microscopy, and mass spectrometry. Steroid receptor
      dependent interactions with mitochondria may include transcriptional regulation
      of nuclear DNA-encoded mitochondrial proteins, transcriptional regulation of
      mitochondrial DNA-encoded proteins, or indirect effects on mitochondria due to
      interactions with cytoplasmic signaling peptides and non-genomic control of
      cation fluxes. These interactions may play a role in mitochondrial-dependent
      processes of oxidative phosphorylation and apoptosis. Physiological examples of
      these interactions are discussed.

PMID- 17447206
TI  - Membrane-initiated signaling of estrogen in the brain.
AB  - It is well known that many of the actions of estrogen in the central nervous
      system are mediated via intracellular receptor/transcription factors that
      interact with steroid response elements on target genes. However, there now
      exists compelling evidence for membrane steroid receptors for estrogen in
      hypothalamic and other brain neurons. It is not well understood how estrogen
      signals via membrane receptors, and how these signals influence not only membrane
      excitability but also gene transcription in neurons. Indeed, it has been known
      for some time that estrogen can rapidly alter neuronal activity within seconds,
      indicating that some cellular effects can occur via membrane-delimited events. In
      addition, estrogen can affect second messenger systems including calcium
      mobilization and a plethora of kinases to alter cell signaling. Therefore, this
      review considers our current knowledge of rapid membrane-initiated and
      intracellular signaling by estrogen in the brain, and the nature of receptors
      involved and how they contribute to homeostatic functions.

PMID- 17447207
TI  - Non-genomic sex steroid actions in the vascular system.
AB  - Sex steroid receptors (SRs) traditionally have been regarded as transcription
      factors regulating the expression of target genes. However, alternative
      mechanisms of signal transduction have been identified recently. These actions of
      sex steroids do not require gene expression or protein synthesis and are
      independent of the nuclear localization of the receptors. Indeed, some of these
      actions are elicited by SRs at the plasma membrane. In the recent years
      significant advances have been made in the characterization of these rapid
      actions of sex steroids in the vascular system. Prototypical non-genomic actions
      of sex steroids at this level include the induction of rapid vasodilatation as
      well as anti-inflammatory and antiatherogenic actions. Ubiquitous signaling
      pathways traditionally believed to mediate the signals of growth factors or
      cytokines have been found to be recruited by sex steroid hormones via their
      receptors. These include tyrosine kinases, c-Src, G proteins,
      phosphatidylinositol 3-OH kinase/Akt, and mitogen-activated protein kinases.
      These cascades lead to rapid actions, such as the activation of nitric oxide
      synthesis, but are also critical for the regulation of the expression of several
      target genes in the nucleus, indicating a tight integration of the non-genomic
      and genomic pathways of sex steroid signaling. The understanding of the molecular
      basis of the non-genomic actions of sex steroids on the vascular system is
      important, and may become relevant for clinical purposes in the future.

PMID- 17447208
TI  - Membrane-initiated steroid signaling action of estrogen and breast cancer.
AB  - Although classical concepts had assigned priority to the nuclear-initiated
      steroid signaling pathway of estrogen receptor (ER), recent studies document that
      the ER also possesses the membrane-initiated steroid signaling (MISS) pathway. A
      small fraction of ER is associated with the cell membrane and mediates the rapid
      effects of estrogen. Unlike classical growth factor receptors, such as
      insulinlike growth factor 1 receptor and epidermal growth factor receptor, ER has
      no transmembrane and kinase domains. Instead, the initiating signals of MISS
      action of ER require a rapid formation of ER-centered protein complexes with many
      signaling molecules, leading to the activation of mitogen-activated protein
      kinase and Akt signaling pathways. In this review, we focus on the MISS action of
      ER and its role in the development of hormone resistance in breast cancer. A full
      understanding of the mechanisms, with the ultimate aim of abrogating specific
      steps, should lead to more targeted strategies for treatment of hormone-dependent
      breast cancer.

PMID- 17447209
TI  - Non-genomic actions of progesterone in the normal and neoplastic mammalian ovary.
AB  - This review summarizes recent findings on the non-genomic or membrane-initiated
      actions of progesterone that regulate the function of the normal and neoplastic
      mammalian ovary. This review focuses on three receptors: the classic progesterone
      receptor, the membrane progesterone receptors (MPRalpha, beta, and gamma) that
      were initially cloned from seatrout ovaries, and a progesterone binding protein
      referred to as progesterone receptor membrane component-1 (PGRMC1). Specifically,
      the structure of each of these receptors is compared and related to their
      capacity to activate various signal transduction pathways. Then the biological
      effects of P4 on the function of granulosa cells, luteal cells, ovarian surface
      epithelial cells, and ovarian cancers that are derived from the ovarian surface
      epithelial cells are discussed in relationship to the expression of each of these
      receptors. Whenever possible, studies involving human cells and tissues are
      presented, although data from other mammalian species are used to supplement the
      human studies to provide a more complete picture of this complex and rapidly
      developing area of membrane-initiated actions of progesterone.

PMID- 17447210
TI  - Non-genomic steroid actions in human spermatozoa. "Persistent tickling from a
      laden environment".
AB  - As sperm traverse the female tract from vagina to oocyte, they experience a
      steroid milieu, which due to transcriptional inactivity, they can only respond to
      via non-genomic signaling. This environment mediates events including
      capacitation, changes in motility patterns, chemotaxis, and acrosome reaction.
      Current knowledge of the events, calcium signaling pathways, and potential
      identity of receptors involved is reviewed in light of recent data, with a
      context for further work in the field, and emphasizing the importance of steroids
      as a mixed stimulant. Progesterone receptor candidates are considered in light of
      recent findings, including novel classes of receptors such as a progesterone
      membrane receptor component-1 or -2 complex with serpine-1 mRNA binding protein,
      the best candidate so far for progesterone activity in human sperm. Given the
      number of other alternative candidates and the apparent diversity of the
      signaling pathways activated, the presence of multiple species of progesterone
      receptors should not be excluded. Given that sperm dysfunction is the most common
      defined cause of infertility, advances in our currently limited knowledge of
      these pathways and events are crucial to not only create better therapies but
      also improve rational diagnosis.

PMID- 17447211
TI  - [Vocal Cord Dysfunction--what do we really know? A review].
AB  - Vocal Cord Dysfunction (VCD), intermittent dyspnoea attacks caused by episodic
      paradoxical adduction of the vocal cords, plays an important role in the
      differential diagnosis of so called intractable or difficult to control bronchial
      asthma. The clinical symptoms may mimic asthma, resulting in high dose
      medications that often lead to considerable iatrogenic induced morbidity e. g.
      high dose systemic corticosteriods. In most cases VCD cannot be demonstrated
      using common diagnostic methods, due to self-limiting symptoms of less than one
      to two minutes. A typical VCD-patient presents with seemingly life-threatening
      dyspnoea with negative diagnostic results for asthma or other standard airway
      disorders and lack of improvement with standard medications. The frustrating
      clinical course can induce significant psychiatric disorders such as anxiety and
      panic attacks in VCD-patients. Increased knowledge of the characteristic clinical
      symptoms of vocal cord dysfunction can help physicians identify the correct
      diagnosis even without further testing. VCD should be seen as a challenge to
      every pulmonologists. Early diagnosis prevents prolonged clinical courses
      including negative effects due to medication as well as economical consequences.
      The aim of this paper is to present and to discuss the current understandings of
      the clinical and pathophysiological aspects of this disease.

PMID- 17447212
TI  - [Ventilation and analgo-sedation].
AB  - Every patient receiving invasive mechanical ventilation needs an adequate
      analgesia and sedation. Based on validated scores, the individual titration of
      sedation and analgesia aims to maximise patient comfort and optimise patient
      ventilator synchrony. By regular re-evaluation (e. g., three times a day) of the
      drug doses a day-night-time rhythm, with a deeper sedation during the night, can
      be achieved. It is important to know that the recommendations concerning the drug
      doses are often based on a single application, which does not reflect the real
      elimination kinetics of a continuous drug delivery. This may significantly change
      in critically ill patients. Using a modern concept of analgo-sedation, it is
      often possible to establish spontaneous breathing during mechanical ventilation
      and to promote successful early weaning of the patient.

PMID- 17447213
TI  - [Nature as a sanatorium and pedagogical place. The Waldschule and open-air
      schools and their development in the first half of the 20th century].

PMID- 17447214
TI  - The four-chamber view in fetal echocardiography.

PMID- 17447215
TI  - [The extended repertoire of sonography: contrast enhancement, radio frequency
      ablation and puncture].

PMID- 17447216
TI  - Characterization and detection of hepatocellular carcinoma (HCC): comparison of
      the ultrasound contrast agents SonoVue (BR 1) and Levovist (SH U 508A)-
      comparison of SonoVue and Levovist in HCC.
AB  - PURPOSE: SonoVue and Levovist (SH U 508A) are both ultrasound contrast agents,
      which are helpful in characterization and detection of malignant liver lesions.
      This study was performed to compare both contrast agents according to the
      capability to diagnose hepatocellular carcinoma (HCC). MATERIALS AND METHODS: In
      a prospective study, 65 patients with histologically proven hepatocellular
      carcinoma (HCC) were examined with both, Levovist and SonoVue. In all patients
      HCC lesions had been detected by B-mode sonography before the study start. After
      injection of 2.4 ml SonoVue i. v., the liver was examined continuously for up to
      three minutes using "low MI"-pulse inversion sonography. For the Levovist
      examinations 2.5 g Levovist were injected i. v. After a delay of at least 2.5
      minutes without scanning, the liver was examined with three different scans using
      "high-MI"-pulse-inversion sonography. RESULTS: The examination was technically
      sufficient in 98% after SonoVue-injection and in 92% after Levovist-injection (n.
      s.). Comparison of the results was performed for the 60/65 patients (61 lesions),
      in which both methods were technically sufficient. After SonoVue-injection
      contrast-enhancement in the arterial phase was found in 79% (48/61) of the
      lesions. Demarcation of the HCC-lesion in the late phase was found in 89% of the
      SonoVue-examinations and in 98% of the Levovist-examinations (p < 0.05). Early
      SonoVue-enhancement and/or demarcation in SonoVue late-phase was found in 93% of
      the HCC-lesions (n. s. compared to Levovist-late phase). CONCLUSION: Levovist
      late phase has a higher sensitivity in predicting lesion dignity of HCC-lesions
      compared to SonoVue-late phase, but not compared to combination of SonoVue-early
      phase and late phase.

PMID- 17447217
TI  - [Prolonged survival through combined treatment with radiofrequency
      ablation/ethanol instillation compared with radiofrequency ablation alone in the
      VX2 rabbit liver tumour model].
AB  - Combination of radiofrequency ablation (RFA)/ethanol instillation (EI) leads to
      higher survival rates compared to single RFA for the treatment of VX2 liver
      tumours in a rabbit tumour model. INTRODUCTION: To improve the outcome and
      survival rates of RFA in treatment of liver tumours, a comparative study of RFA
      with or without EI was performed. MATERIAL AND METHODS: We implanted a single
      tumour in the liver of 46 rabbits. After 20 days, animals were treated with
      RFA/EI or RFA alone. The animals were observed for a maximum of 110 days, after
      which an autopsy was conducted. RESULTS: 30 animals of the RFA group and 16 of
      combination therapy were analysed. After interim analysis with the Kaplan-Meier
      method, a significantly higher survival rate for the combination therapy was
      observed (P = 0.004). Following the study design, the experiment was therefore
      terminated ahead of schedule. Rate of metastasis (M) and local recurrence (LR)
      did not differ between the combination or RFA alone. CONCLUSION: RFA/EI is
      superior to treatment with RFA alone with regard to survival rates.

PMID- 17447218
TI  - Percutanous and intraoperative ultrasound-guided radiofrequency ablation of
      hepatic tumours.
AB  - PURPOSE: Ultrasonography (US)-guided Radiofrequency ablation (RFA) is
      increasingly used to treat liver tumours. The aim of this study was to evaluate
      the impact of multidisciplinary patient selection on clinical results. MATERIALS
      AND METHODS: From January 2002 to December 2004, 69 consecutive patients with
      malignant hepatic tumours were presented to our clinic for RFA-treatment. After a
      multidisciplinary tumour board decision, 33 patients (47.8%) with 70 liver
      tumours underwent RFA using a 14-gauge needle electrode via a percutaneous (26)
      or surgical (7) approach, either alone or combined with resection (3) or
      chemoembolisation (3). 36 patients (52.2%) were excluded from RFA treatment,
      mainly because of extensive disease or failure of prior chemotherapy. With a
      median of 20 months (range 6 - 42 months), all 69 patients were followed
      clinically to assess survival, and the 33 patients who received additional
      treatment were examined by contrast-enhanced CT to assess local success. RESULTS:
      Complete necrosis was obtained in 64/70 of ablated tumours (91.4%).The
      corresponding mean sizes (ranges) of lesion vs. necrosis achieved were 2.3 cm
      (0.9 - 5.0) vs. 3.7 cm (2.1 - 5.7). Two complications (6.6%) occurred, including
      one liver abscess and one postablational syndrome. At the time of the tumour
      board decision, the RFA (33) and non-RFA (36) group differed in mean sizes of
      tumours (2.3 vs. 3.5 cm), average tumours per patient (2.1 vs. 3.8), and failure
      of prior chemotherapy (2/33 vs. 22/36). From 36 patients judged to be ineligible
      for RFA, 24 (66.6%) underwent RFA at another institution. When comparing survival
      of patients who underwent RFA at our institution (33) vs. those who underwent RFA
      outside (24) vs. those who underwent no RFA (12), 1/33 (3%) vs. 9/24 (37.5%) vs.
      8/12 (66.6%) died within 6 month and 27/33 (81.2%) vs. 5/24 (29.2%) vs. 2/12
      (16.7%) were alive after 20 months median follow up. CONCLUSION: US-guided RFA
      offers a safe local treatment option to destroy small liver tumours (< 3 cm).
      Carefully and multidisciplinary selected patients may derive benefit, but
      uncritical application leads to unsatisfying clinical results.

PMID- 17447219
TI  - Spontaneous bleeding from the uterine arteries during pregnancy--problems in
      diagnosis and therapy--bleeding from uterine arteries during pregnancy.
AB  - Arterial bleeding, initially negative on MRI, ultrasonography and radiographic
      angiography, complicated the course of pregnancy with severe and recurrent
      vaginal and pelvic haemorrhage in the second trimester. Bleeding from the left
      uterine artery was successfully terminated by angiographic embolisation. No
      harmful effects on the fetal well-being were recorded after the embolisation.
      Massive haemorrhage, most probably from the right uterine artery, recurred some
      days later, and Caesarean section was performed. At postpartal ultrasonography
      and catheter angiography, massive arterial bleeding from a pseudoaneurysmatic
      vessel was clearly imaged on the right side of the cervical myometrium and could
      successfully be treated by radiographic embolisation. Though the primary
      aetiology of bleeding remains uncertain, it is possible that cervical
      endometriosis could have been associated with this complication.

PMID- 17447220
TI  - [Is there still an increase in knowledge in basic abdominal ultrasound?--congress
      report DLT Graz 2006].
AB  - The number of articles on abdominal ultrasound has been declining in the last few
      years. The proportion of presentations containing significant new developments
      amongst the 23 submitted papers which were accepted is low, some presentations
      are partially new or utilise ultrasound as a clinical tool, and about half the
      articles have already been presented in a different form or context at former
      meetings. Without contrast enhanced ultrasound, innovative contributions would be
      a rarity. The following article summarises the scientific meetings of the DLT in
      Graz. In addition to a short evaluation, the scientific objectives of abdominal
      ultrasound in the next few years are discussed.

PMID- 17447221
TI  - Effect of preoperative administration of tepoxalin on induction dose of
      injectable anesthetics in dogs.
AB  - Medications given preoperatively have the potential to affect the induction dose
      of injectable anesthetics, which could result in an anesthetic overdose.
      Tepoxalin is an NSAID approved for the treatment of arthritis in dogs in the
      United States and hence could be administered in patients requiring anesthesia.
      In this study, administration of a single dose or a 10-day course of tepoxalin
      did not affect the induction dose (dose that allowed intubation) of propofol,
      thiopental, or ketamine-diazepam and also did not affect the time required for
      dogs to recover from anesthesia.

PMID- 17447222
TI  - Effects of reconcile (fluoxetine) chewable tablets plus behavior management for
      canine separation anxiety.
AB  - Canine separation anxiety is a common behavioral problem presented to
      veterinarians. Associated behaviors are distressing to both dog and owner, have
      the potential to disrupt the human-companion animal bond, and may lead to
      euthanasia. The results of this study demonstrate the clinical efficacy and
      safety of Reconcile (fluoxetine, 1 to 2 mg/kg/day [0.45 to 0.91 mg/lb/day]), in
      conjunction with behavior management, for the treatment of canine separation
      anxiety. The beef flavored chewable formulation was palatable to treated dogs and
      easy to administer. This study provides to veterinarians and owners valuable
      information about an effective separation anxiety treatment plan that combines
      use of Reconcile with behavior modification.

PMID- 17447223
TI  - Comparison of the mucosal immune response in dogs vaccinated with either an
      intranasal avirulent live culture or a subcutaneous antigen extract vaccine of
      Bordetella bronchiseptica.
AB  - Healthy dogs with low antibody titer to Bordetella bronchiseptica were vaccinated
      intranasally with an avirulent live vaccine, subcutaneously with an antigen
      extract vaccine, or subcutaneously and intranasally with a placebo. Intranasally
      vaccinated dogs developed B. bronchiseptica-specific IgA titers in nasal
      secretions that remained at high levels until the end of the study; dogs
      vaccinated subcutaneously with the antigen extract or placebo did not develop
      measurable antigen-specific IgA titers in nasal secretions. Dogs were challenged
      with virulent live B. bronchiseptica 63 days after vaccination. Intranasally
      vaccinated dogs had significantly lower cough scores (P < or =.0058) and shed
      significantly fewer challenge organisms (P <.0001) than dogs in either of the
      other groups. Cough scores of subcutaneously vaccinated dogs were not
      significantly different from placebo-vaccinated dogs.

PMID- 17447224
TI  - Firocoxib efficacy preventing urate-induced synovitis, pain, and inflammation in
      dogs.
AB  - This positive-control study evaluated the efficacy of firocoxib versus carprofen,
      deracoxib, and meloxicam for the prevention of pain and inflammation in a urate
      crystal synovitis model of lameness. Lameness scoring and force plate gait
      analysis were used to assess efficacy. The resulting lameness scores and force
      plate ground reaction forces after urate crystal injection were not significantly
      different among the groups. Relative to each group's baseline (nonlame) score,
      only the firocoxib group was not significantly lame, based on lameness score, at
      the model's peak effect.

PMID- 17447225
TI  - Oxygenation in medetomidine-sedated dogs with and without 100% oxygen
      insufflation.
AB  - Oxygenation status was evaluated in medetomidine-sedated dogs breathing room air
      (M) or 100 percent oxygen (MO2). Medetomidine (40 microg/kg IV) administration
      resulted in peripheral vasoconstriction and decreased venous saturation as
      measured by an increased oxygen extraction ratio in peripheral tissues. Providing
      100 percent oxygen insufflation via face mask reduced desaturation by increasing
      oxygen content but did not prevent vasoconstriction or reduce the oxygen
      extraction ratio in peripheral tissues. Atipamezole (200 microg/kg IV) reversed
      medetomidine-induced vasoconstriction and increased oxygen supply to tissues as
      indicated by a lower tissue oxygen extraction ratio. The authors conclude that
      100 percent oxygen insufflation via face mask during medetomidine sedation (40
      micrograms/kg [corrected] IV) benefits tissue oxygenation in healthy dogs.

PMID- 17447226
TI  - Safety of elevated dosages of a 0.24% diflubenzuron pellet administered orally to
      horses.
AB  - The safety of a feed-thru pellet formulation containing the insect growth
      regulator diflubenzuron (0.24%) for control of manure-breeding flies (Musca
      domestica L. and Stomoxys calcitrans L.) in horses was evaluated. Pellets were
      administered orally at 0, 1, 3, and 5 times the clinical dosage (0.12 to 0.20
      mg/kg) on a daily basis for 31 consecutive days. Variables examined included
      daily clinical observations, hematology, coagulation, serum chemistry,
      acetylcholinesterase inhibition, body weights, and physical examinations. Horses
      remained healthy throughout the study, and no adverse reactions or events related
      to the pellets were observed. Statistically significant differences (P < or =
      0.10) between dose groups (0x, 1x, 3x, and 5x) were observed for only four of the
      44 serum chemistry and hematologic variables measured, none of which was dose
      related. Diflubenzuron can be safely administered orally to horses at 0.12 to
      0.20 mg/kg for control of manure-breeding flies.

PMID- 17447227
TI  - Pharmacokinetics and in vitro effects of tegaserod, a serotonin 5
      hydroxytryptamine 4 (5-HT4) receptor agonist with prokinetic activity in horses.
AB  - Tegaserod, a serotonin agonist, has been shown to have prokinetic effects in
      horses, but pharmacokinetic information is not currently available. The
      pharmacokinetics and in vitro effects of tegaserod were evaluated. Tegaserod
      increased the contractile activity of smooth muscle preparations of the equine
      pelvic flexure. Pertinent pharmacokinetic parameters for a single IV and oral
      dose were determined. Therapeutic plasma concentrations of tegaserod were
      achieved by a single oral dose at 0.27 mg/kg. These findings indicate that
      further clinical studies are warranted to investigate potential benefits in cases
      of functional gastrointestinal motility disorders in horses.

PMID- 17447228
TI  - Onset of protection from experimental infection with type 2 bovine viral diarrhea
      virus following vaccination with a modified-live vaccine.
AB  - The onset of protection after the administration of a modified-live bovine viral
      diarrhea virus (BVDV) vaccine was determined. Protection was determined following
      experimental infection with a virulent type-2 BVDV (strain 1373) in cattle
      vaccinated 3, 5, or 7 days before BVDV infection. Protection, as measured by
      reduced virus shedding, lack of leukopenia, reduction in viremia, and reduced
      mortality, was present as early as 3 days after vaccination with a single dose of
      modified-live BVDV vaccine. Complete protection was obtained in cattle vaccinated
      5 or 7 days before BVDV experimental infection.

PMID- 17447231
TI  - Increasing research in the European Union.

PMID- 17447229
TI  - Are there predictors of outcome in depressed elderly nursing home residents
      during treatment with mirtazapine orally disintegrating tablets?
AB  - BACKGROUND: Treatment studies of depression in residential care are limited.
      Reports of predictors of response are rare. In the largest nursing home
      prospective antidepressant trial reported, we examined predictors of response.
      METHODS: This was a 12-week open-label study of mirtazapine orally disintegrating
      tablets performed in 30 US nursing homes. Subjects were men and women aged
      >or=70, with a Mini Mental State Exam (MMSE) score >or=10, who had a depressive
      disorder that required antidepressant treatment. Mirtazapine was started at 15 mg
      at bedtime, and adjusted to 15-45 mg/day. A 16-item Hamilton Depression Rating
      Scale was used to assess depression at baseline, weeks 2, 4, 8, and 12 or early
      termination. RESULTS: One hundred and twenty-four patients received at least one
      dose of study drug and of these, 119 had at least one post-drug assessment. Mean
      age was 82.9 years and 72% were female. Response rates at 12 weeks were 47% on
      the HAMD and 54% on the CGI. Age, sex, MMSE score, medical burden, history of
      prior depression, and baseline HAMD severity were not significantly associated
      with HAMD response (>or=50% improvement) and in most cases correlations were
      trivial, <0.1. Advanced age, medical burden, and cognitive impairment did not
      predict adverse events. CONCLUSIONS: In this sample of depressed nursing home
      residents treated with mirtazapine orally disintegrating tablets, advanced age,
      medical illness, and cognitive impairment did not predict response. The findings
      suggest that these variables need not be viewed as obstacles to treatment.

PMID- 17447232
TI  - NK cells--from basic research to cancer therapy.
AB  - 50 scientists recently met for the Hengstberger Symposium on NK cells in
      Heidelberg, Germany to discuss the regulation and function of these important
      immune cells.

PMID- 17447233
TI  - Helminths, allergic disorders and IgE-mediated immune responses: where do we
      stand?
AB  - Th2 responses induced by allergens or helminths share many common features.
      However, allergen-specific IgE can almost always be detected in atopic patients,
      whereas helminth-specific IgE is often not detectable and anaphylaxis often
      occurs in atopy but not helminth infections. This may be due to T regulatory
      responses induced by the helminths or the lack of helminth-specific IgE.
      Alternatively non-specific IgE induced by the helminths may protect from mast
      cell or basophil degranulation by saturating IgE binding sites. Both of these
      mechanisms have been implicated to be involved in helminth-induced protection
      from allergic responses. An article in the current issue of the European Journal
      of Immunology describes the generation of an anti-Nippostrongylus brasiliensis
      specific IgE antibody which was used to identify a novel N. brasiliensis antigen
      (Nb-Ag1). The authors demonstrated that Nb-Ag1 specific IgE could only be
      detected for a short period of time during infection, and that these levels were
      sufficient to prime mast cells thereby leading to active cutaneous anaphylaxis
      after the application of Nb-Ag1. This is the first report clearly showing that a
      low level of helminth-specific IgE, transiently produced, is able to induce mast
      cell degranulation in the presence of large amounts of polyclonal IgE.

PMID- 17447234
TI  - Determining restriction digest efficiency using the SNaPshot single-base
      extension method and CE.
AB  - Incomplete restriction endonuclease digestion may cause complications during
      particular applications, where any undigested product may interfere with
      genotyping accuracy, cloning efficiency or PCR amplification. In some instances
      it may be useful to measure the amount of undigested DNA remaining in the sample,
      allowing redigestion or elimination of unsuitable samples. A single-base
      extension SNP genotyping method (SNaPshot, Applied Biosytems) was adapted to
      interrogate restriction sites and their digestibility. The digested DNA was
      amplified by nested PCR to specifically amplify sections containing the
      restriction sites of interest. Single interrogation primers, terminating
      immediately 5' of the cleavage site, were used in conjunction with the SNaPshot
      multiplex system and CE to detect intact, amplifiable product remaining in the
      digest. This method detected as little as 10 pg of intact DNA, within a larger
      proportion of digested DNA. Across two different restriction enzymes, the amount
      remaining undigested was found to be dependent on the amount of DNA, ranging from
      0.08% with 200 ng to 1.25% with 600 ng.

PMID- 17447235
TI  - On-capillary sample cleanup method for the electrophoretic determination of
      carbohydrates in juice samples.
AB  - On many occasions, sample treatment is a critical step in electrophoretic
      analysis. As an alternative to batch procedures, in this work, a new strategy is
      presented with a view to develop an on-capillary sample cleanup method. This
      strategy is based on the partial filling of the capillary with carboxylated
      single-walled carbon nanotube (c-SWNT). The nanoparticles retain interferences
      from the matrix allowing the determination and quantification of carbohydrates
      (viz glucose, maltose and fructose). The precision of the method for the analysis
      of real samples ranged from 5.3 to 6.4%. The proposed method was compared with a
      method based on a batch filtration of the juice sample through diatomaceous earth
      and further electrophoretic determination. This method was also validated in this
      work. The RSD for this other method ranged from 5.1 to 6%. The results obtained
      by both methods were statistically comparable demonstrating the accuracy of the
      proposed methods and their effectiveness. Electrophoretic separation of
      carbohydrates was achieved using 200 mM borate solution as a buffer at pH 9.5 and
      applying 15 kV. During separation, the capillary temperature was kept constant at
      40 degrees C. For the on-capillary cleanup method, a solution containing 50 mg/L
      of c-SWNTs prepared in 300 mM borate solution at pH 9.5 was introduced for 60 s
      into the capillary just before sample introduction. For the electrophoretic
      analysis of samples cleaned in batch with diatomaceous earth, it is also
      recommended to introduce into the capillary, just before the sample, a 300 mM
      borate solution as it enhances the sensitivity and electrophoretic resolution.

PMID- 17447236
TI  - Site-specific protein immobilization in a microfluidic chip channel via an IEF
      gelation process.
AB  - A novel strategy for site-specific protein immobilization via combining chip IEF
      with low-temperature sol-gel technology, called IEF-GEL here, in the channel of a
      modified poly(methyl methacrylate) (PMMA) microfluidic chip is proposed in this
      work. The IEF-GEL process involves firstly IEF for homogeneously dissolved
      protein in PBS containing alumina sol and carrier ampholyte with prearranged pH
      gradient, and then gelation locally for protein encapsulation. The process and
      feasibility of proposed IEF-GEL were investigated by EOF measurements,
      fluorescence microscopic photography, Raman spectrum and further demonstrated by
      glucose oxidase (GOx) reactors integrated with end-column electrochemical
      detection. Site-controllable immobilization of protein was realized in a 30 mm
      long microfluidic chip channel by the strategy to create a approximately 1.7 mm
      concentrated FITC-BSA band, which leads to great improvement of the elute peak
      shape, accomplished with remarkably increased sensitivity, approximately 20 times
      higher than that without IEF-GEL treatment to GOx reactors. The kinetic response
      of GOx after IEF-GEL treatment was also investigated. The proposed system holds
      the advantages of IEF and low-temperature sol-gel technologies, i.e.
      concentrating the protein to be focused and retaining the biological activity for
      the gel-embedded protein, thus realizes site-specific immobilization of low
      concentration protein at nL volume level.

PMID- 17447237
TI  - Tris interference in IEF and 2-DE.
AB  - When dried IPGs are hydrated with protein solutions, the concentration of protein
      and other ionic constituents is constant throughout the strip. Tris, initially
      present at a very low concentration, focuses during IEF and accumulates in the
      gradient at a pH corresponding to its pK(a) at the operative temperature of
      electrophoresis. Tris focuses more rapidly than many basic proteins, and
      concentrates into a localized zone of increased conductivity which coincides with
      a precipitous voltage drop in that vicinity. Basic proteins, already near their
      pI, are frequently observed to align at the periphery of this zone. Acidic
      proteins imbibed at the basic end of the gradient must traverse this region
      before this ionic boundary is formed, or otherwise may fail to migrate to their
      proper positions in the pH gradient.

PMID- 17447238
TI  - 2-DE proteomic analysis of the model cyanobacterium Anabaena variabilis.
AB  - Cyanobacteria are photosynthetic bacteria capable of producing hydrogen and
      secondary metabolites with potential pharmaceutical applications. A limited
      number of cyanobacterial 2-DE proteomic studies have been published, most of
      which are based on Synechocystis sp. PCC 6803. Here, we report the use of 2-DE,
      ESI-MS/MS and protein bioinformatics tools to characterize the proteome of
      Anabaena variabilis ATCC 29413, a heterocystous nitrogen-fixing cyanobacterium
      that is a model organism for the study of nitrogen fixation. Using a 2-DE
      workflow that included the use of a detergent-based extraction buffer and 3-10
      nonlinear IPG strips resulted in the identification of 254 unique proteins, with
      significantly better coverage of basic and low-abundance proteins that has been
      reported in 2-DE analyses of Synechocystis sp. A set of protein bioinformatics
      tools was employed to provide estimates of protein localization, hydrophobicity,
      abundance and other properties. The characteristics of the A. variabilis proteins
      identified in this study were compared against the theoretical proteome for this
      organism, and more generally within the cyanobacteria, to identify opportunities
      for further development of 2-DE-based cyanobacterial proteomics.

PMID- 17447239
TI  - Carbon fiber nanoelectrodes applied to microchip electrophoresis amperometric
      detection of neurotransmitter dopamine in rat pheochromocytoma (PC12) cells.
AB  - Microelectrodes have been adopted in electrochemical detection for CE or
      microchip CE in recent years. In this paper, the use of nanoelectrodes (with tip
      diameter of 100-300 nm) as the electrochemical detector in microchip CE is
      firstly reported. The experimental results indicated that both the sensitivity
      and resolution of microchip CE with the carbon fiber nanoelectrode (CFNE)
      amperometric detection have been improved markedly comparing with the traditional
      microelectrodes. The detection limit of dopamine (S/N = 3) is 5.9x10(-8) M, which
      is one or two orders of magnitude lower than that reported so far, and the
      resolution of dopamine (DA) and isoprenaline (IP) has also improved from 0.6
      (using 7 mum carbon fiber microelectrodes, CFME) to 1.0. We assembled a novel and
      easily operated microchip CE system with end-column amperometric detection, which
      allows the convenient and fast replacement of the passivated electrodes. Under
      the optimized condition, the RSDs of peak height and migration time are 1.47 and
      0.31%, respectively (n = 40), indicating that the system displays excellent
      reproducibility. The nanoelectrode-based microchip CE system has been
      successfully applied to the determination of DA in cultured rat pheochromocytoma
      (PC12) cells, and the average content of DA in an individual PC12 cell is 0.54 +/
      0.07 fmol, which is in good agreement with that reported in the literature.

PMID- 17447240
TI  - Determination of neurotransmitters in PC 12 cells by microchip electrophoresis
      with fluorescence detection.
AB  - A sensitive fluorescence detection system with an Hg-lamp as the excitation
      source and a photon counter as the detector for microchip CE (MCE) has been
      developed. O-Phthaldialdehyde (OPA, lambda(ex) = 340 nm) was employed to label
      the catecholamine neurotransmitters such as dopamine (DA), norepinephrine (NE),
      and amino acid neurotransmitters including alanine (Ala), taurine (Tau), glycine
      (Gly), glutamic acid (Glu), and aspartic acid (Asp). The separation of seven
      derivatized neurotransmitters was successfully performed in MCE and the detection
      limits (S/N = 3) for DA, NE, Ala, Tau, Gly, Glu, and Asp were 0.85, 0.49, 0.23,
      0.15, 0.13, 0.18, and 0.29 fmol, respectively. The system was then successfully
      applied for separation and determination of neurotransmitters in rat
      pheochromocytoma (PC 12) cells, and the average amounts of analyte per cell from
      a cell population were 2.5 fmol for DA, 3.3 fmol for Ala, 8.2 fmol for Tau, 4.0
      fmol for Gly, and 1.9 fmol for Glu, respectively. By single-cell injection mode,
      electrophoresis separation and quantitative measurement of Glu in individual PC
      12 cells was obtained. The average value of Glu per cell from single PC 12 cells
      analysis was found to be 3.5 +/- 3.1 fmol.

PMID- 17447241
TI  - Study of injection bias in a simple hydrodynamic injection in microchip CE.
AB  - The electrokinetically pinched method is the most commonly used mode for sample
      injection in microchip capillary electrophoresis (microCE) due to its simplicity
      and well-defined sample volume. However, the limited injection volume and the
      electrophoretic bias of the pinched injection may limit its universal usage to
      specific applications. Several hydrodynamic injection methods in microCE have
      been reported; however, almost all claimed that their methods are bias-free
      without considering the dispensing bias. To investigate the dispensing bias, a
      simple hydrodynamic injection was developed in single-T and double-T glass
      microchips. The sample flow was produced by hydrostatic pressure generated by the
      liquid level difference between the sample reservoir and the other reservoirs.
      The reproducibility of peak area and peak area ratio was improved to a
      significant extent using large-surface reservoirs for the buffer reservoir and
      the sample waste reservoir to reduce the Laplace pressure effect. Without a
      voltage applied on the sample solution, the voltage-related sample bias was
      eliminated. The dispensing bias was analyzed theoretically and studied
      experimentally. It was demonstrated that the dispensing bias existed and could be
      reduced significantly by appropriately setting up the voltage configuration and
      by controlling the appropriate liquid level difference.

PMID- 17447242
TI  - Simultaneous determination of Zr(IV) and Hf(IV) by CE using precolumn
      complexation with a [PW(11)O(39)](7-) ligand.
AB  - A CE method was developed for the simultaneous determination of Zr(IV) and Hf(IV)
      at trace levels. A lacunary Keggin-type [PW(11)O(39)](7-) ligand reacted
      quantitatively with a mixture of trace amounts of Zr(IV) and Hf(IV) to form the
      so-called ternary Keggin-type anions [P(Zr(IV)W(11))O(40)](5-) and
      [P(Hf(IV)W(11))O(40)](5-) in 0.010 M monochloroacetate buffer (pH 2.2). Since
      both ternary anions possessed different electrophoretic mobilities and high molar
      absorptivities in the UV region, Zr(IV) and Hf(IV) were determined simultaneously
      with direct UV detection at 258 nm. Each peak height was linearly dependent on
      the concentration of Zr(IV) or Hf(IV) in the range of 5.0x10(-7)-1.0x10(-5) M; a
      detection limit of 2x10(-7) M was achieved. The utility of the proposed CE method
      was demonstrated for the simultaneous determination of Zr(IV) and Hf(IV) in
      natural water samples with satisfactory results.

PMID- 17447243
TI  - Quantification of buserelin in a pharmaceutical product by multiple-injection
      CZE.
AB  - An efficient and rapid separation method based on reversed-polarity multiple
      injection CZE (MICZE), has been developed for the quantification of buserelin in
      a pharmaceutical product. The determinations were performed by serially injecting
      five standard solutions of buserelin (50-300 microg/mL) and one reference analyte
      into a Polybrene-coated capillary. All the samples contained goserelin, an analog
      peptide to buserelin, as internal standard (IS). Immediately after pressure
      injection, the applied sample plugs were subjected to electrophoresis for 2 min
      at -25 kV. Consequently, each sample plug became isolated from its neighboring
      plugs by the BGE, composed of 100 mM phosphate-triethanolamine buffer at pH 3.0
      containing 10% v/v ACN. During separation the individual sample components
      migrated at similar velocities and as distinct zones through the capillary giving
      24 peaks, 12 from the analyte and the IS and 12 from the sample matrix. The
      buserelin content of the pharmaceutical product was determined to be 0.94 +/-
      0.05 mg/mL, which is only a slight deviation from the declared concentration (1
      mg/mL).

PMID- 17447244
TI  - High MS-compatibility of silver nitrate-stained protein spots from 2-DE gels
      using ZipPlates and AnchorChips for successful protein identification.
AB  - The availability of easy-to-handle, sensitive, and cost-effective protein
      staining protocols for 2-DE, in conjunction with a high compatibility for
      subsequent MS analysis, is still a prerequisite for successful proteome research.
      In this article we describe a quick and easy-to-use methodological protocol based
      on sensitive, homogeneous, and MS-compatible silver nitrate protein staining, in
      combination with an in-gel digestion, employing the Millipore 96-well ZipPlate
      system for peptide preparation. The improved quality and MS compatibility of the
      generated protein digests, as compared to the otherwise weakly MS-compatible
      silver nitrate staining, were evaluated on real tissue samples by analyzing 192
      Coomassie-stained protein spots against their counterparts from a silver-stained
      2-DE gel. Furthermore, the applicability of the experimental setup was evaluated
      and demonstrated by the analysis of a large-scale MALDI-TOF MS experiment, in
      which we analyzed an additional ~1000 protein spots from 2-DE gels from mouse
      liver and mouse brain tissue.

PMID- 17447245
TI  - Estimation of inhomogeneous zeta potential using velocity measurements of EOF.
AB  - We have developed a method of estimating the zeta potential distribution along
      the microchannel wall using velocity measurements of the EOF. The relevant
      inverse problem is solved through the minimization of a performance function
      utilizing the conjugate gradient method. Employing a set of simulated velocity
      measurements, which is constructed by adding random noise to the computed exact
      velocity, the present method is found to estimate the distribution of the zeta
      potential along the channel wall with reasonable accuracy.

PMID- 17447246
TI  - On-line preconcentration of weak electrolytes by electrokinetic accumulation in
      CE: experiment and simulation.
AB  - A new on-line preconcentration technique was developed that makes possible to
      determine nanomolar concentrations of weak acidic analytes in CE. The method
      consists of long-running electrokinetic sample injection and stacking
      (electrokinetic immobilization) of the analytes at a boundary of two electrolytes
      with different pH values (pH 9.5 and 2.5) and consequent mobilization of the
      stacked uncharged analytes in a micellar system (containing SDS micelles).
      Several factors including buffer concentration, pH, applied voltage, time of
      preconcentration, and SDS concentration were tested to optimize the analysis
      method. An about 4600-fold increase of the sample concentration (in comparison
      with the standard CZE) can be achieved during the preconcentration step. Two
      preservatives applied in food industry -- benzoic acid and sorbic acid were used
      as model samples. The applicability of the proposed method in food analysis was
      demonstrated by determination of nanomolar concentrations of benzoic acid in
      sunflower oil. An extended version of the computer program Simul was used for
      modeling both the preconcentration and mobilization processes taking place in the
      capillary.

PMID- 17447247
TI  - Analysis of fullerene-based nanomaterial in serum matrix by CE.
AB  - With the increasing interest in using nanoparticles as vehicles for drug delivery
      and image contrast agents, there is a need to develop assays for their detection
      and quantitation in complex matrices to facilitate monitoring their
      biodistribution. In this study, we developed a CE approach for the analysis of
      two nanoparticles: carboxyfullerene (C3) and dendrofullerene (DF1) in both
      standard solutions and a serum matrix. These highly soluble, charged C(60)
      derivatives were characterized by CZE using either a bare or dynamically coated
      fused-silica capillaries. The resolution of both nanoparticles was slightly lower
      with the coated capillary; however, their migration times were faster. While
      separation of the DF1 nanoparticles using MEKC resulted in a greater number of
      observable peaks, the peak profile of C3 was basically unchanged regardless of
      whether SDS micelles were added to the running buffers or not. The MEKC and/or
      CZE assays were then used to quantitate the C3 and DF1 nanoparticles in spiked
      human serum samples. The quantitation of the nanoparticles was linear from 0-500
      microg/mL with detection limits ranging from 0.5 to 6 microg/mL.

PMID- 17447248
TI  - Fast evaluation of scaled opposite spin second-order Moller-Plesset correlation
      energies using auxiliary basis expansions and exploiting sparsity.
AB  - The scaled opposite spin Moller-Plesset method (SOS-MP2) is an economical way of
      obtaining correlation energies that are computationally cheaper, and yet, in a
      statistical sense, of higher quality than standard MP2 theory, by introducing one
      empirical parameter. But SOS-MP2 still has a fourth-order scaling step that makes
      the method inapplicable to very large molecular systems. We reduce the scaling of
      SOS-MP2 by exploiting the sparsity of expansion coefficients and local integral
      matrices, by performing local auxiliary basis expansions for the occupied-virtual
      product distributions. To exploit sparsity of 3-index local quantities, we use a
      blocking scheme in which entire zero-rows and columns, for a given third global
      index, are deleted by comparison against a numerical threshold. This approach
      minimizes sparse matrix book-keeping overhead, and also provides sufficiently
      large submatrices after blocking, to allow efficient matrix-matrix multiplies.
      The resulting algorithm is formally cubic scaling, and requires only moderate
      computational resources (quadratic memory and disk space) and, in favorable
      cases, is shown to yield effective quadratic scaling behavior in the size regime
      we can apply it to. Errors associated with local fitting using the attenuated
      Coulomb metric and numerical thresholds in the blocking procedure are found to be
      insignificant in terms of the predicted relative energies. A diverse set of test
      calculations shows that the size of system where significant computational
      savings can be achieved depends strongly on the dimensionality of the system, and
      the extent of localizability of the molecular orbitals.

PMID- 17447249
TI  - Axonal regeneration and development of de novo axons from distal dendrites of
      adult feline commissural interneurons after a proximal axotomy.
AB  - Following proximal axotomy, several types of neurons sprout de novo axons from
      distal dendrites. These processes may represent a means of forming new circuits
      following spinal cord injury. However, it is not know whether mammalian spinal
      interneurons, axotomized as a result of a spinal cord injury, develop de novo
      axons. Our goal was to determine whether spinal commissural interneurons (CINs),
      axotomized by 3-4-mm midsagittal transection at C3, form de novo axons from
      distal dendrites. All experiments were performed on adult cats. CINs in C3 were
      stained with extracellular injections of Neurobiotin at 4-5 weeks post injury.
      The somata of axotomized CINs were identified by the presence of immunoreactivity
      for the axonal growth-associated protein-43 (GAP-43). Nearly half of the CINs had
      de novo axons that emerged from distal dendrites. These axons lacked
      immunoreactivity for the dendritic protein, microtubule-associated protein2a/b
      (MAP2a/b); some had GAP-43-immunoreactive terminals; and nearly all had
      morphological features typical of axons. Dendrites of other CINs did not give
      rise to de novo axons. These CINs did, however, each have a long axon-like
      process (L-ALP) that projected directly from the soma or a very proximal
      dendrite. L-ALPs were devoid of MAP2a/b immunoreactivity. Some of these L-ALPs
      projected through the lesion and formed bouton-like swellings. These results
      suggest that proximally axotomized spinal interneurons have the potential to form
      new connections via de novo axons that emerge from distal dendrites. Others may
      be capable of regeneration of their original axon.

PMID- 17447250
TI  - Spatial and temporal expression of RP58, a novel zinc finger transcriptional
      repressor, in mouse brain.
AB  - RP58, a novel zinc finger protein containing a POZ domain, is a sequence-specific
      transcriptional repressor. To understand the role of this protein, we examined
      RP58 gene expression in the developing mouse brain by quantitative polymerase
      chain reaction (PCR) and in situ hybridization. RP58 mRNA expression was detected
      at embryonic day (E) 10 in the neuroepithelium, and subsequently in the
      ventricular zones of the cerebral cortex in the E12 embryo. Strong expression was
      observed in the preplate in the cerebral cortex from this stage onward. High
      levels of expression continued to be detected in the cortical plate and
      subventricular zone of the neocortex, hippocampus, and parts of the amygdala, but
      not in the thalamus or striatum. These results suggest that RP58 plays a crucial
      role in neuronal proliferation, migration, and differentiation in the developing
      cerebral cortex. RP58 is also expressed in the adult mouse neocortex,
      hippocampus, parts of the amygdala, and granule cells in the cerebellum. Double
      in situ hybridization using GAD67 or VGLUT1 probes revealed that RP58 is
      expressed in glutamatergic excitatory neurons.

PMID- 17447251
TI  - Type 3a and type 3b OFF cone bipolar cells provide for the alternative rod
      pathway in the mouse retina.
AB  - The mammalian retina provides several pathways to relay the information from the
      photoreceptors to the ganglion cells. Cones feed into ON and OFF cone bipolar
      cells that excite ON and OFF ganglion cells, respectively. In the "classical" rod
      pathway, rods feed into rod bipolar cells that provide input to both the ON and
      the OFF pathway via AII amacrine cells. Recent evidence suggests an alternative
      rod pathway in which rods directly contact some types of OFF cone bipolar cells.
      The mouse has become an important model system for retinal research. We performed
      an immunohistochemical analysis on the level of light and electron microscopy to
      identify the bipolar cells and ganglion cells that are involved in the
      alternative rod pathway of the mouse retina. 1) We identify a new bipolar cell
      type, showing that type 3 OFF cone bipolar cells comprise two distinct cell
      types, that we termed 3a and 3b. Type 3a cells express the ion channel HCN4. Type
      3b bipolar cells represent a hitherto unknown cell type that can be identified
      with antibodies against the regulatory subunit RIIbeta of protein kinase A. 2) We
      show that both 3a and 3b cells form flat contacts at cone pedicles and rod
      spherules. 3) Finally, we identify an OFF ganglion cell type whose dendrites
      costratify with type 3a and 3b bipolar cell axon terminals. These newly
      identified cell types represent the basis of a neuronal circuit in the mammalian
      retina that could provide for an alternative fast rod pathway.

PMID- 17447252
TI  - Immunocytochemical analysis of syntaxin-1 in rat circumvallate taste buds.
AB  - Mammalian buds contain a variety of morphological taste cell types, but the type
      III taste cell is the only cell type that has synapses onto nerve processes. We
      hypothesize that taste cell synapses utilize the SNARE protein machinery
      syntaxin, SNAP-25, and synaptobrevin, as is used by synapses in the central
      nervous system (CNS) for Ca2+-dependent exocytosis. Previous studies have shown
      that taste cells with synapses display SNAP-25- and synaptobrevin-2-like
      immunoreactivity (LIR) (Yang et al. [2000a] J Comp Neurol 424:205-215, [2004] J
      Comp Neurol 471:59-71). In the present study we investigated the presynaptic
      membrane protein, syntaxin-1, in circumvallate taste buds of the rat. Our results
      indicate that diffuse cytoplasmic and punctate syntaxin-1-LIR are present in
      different subsets of taste cells. Diffuse, cytoplasmic syntaxin-1-LIR is present
      in type III cells while punctate syntaxin-1-LIR is present in type II cells. The
      punctate syntaxin-1-LIR is believed to be associated with Golgi bodies. All of
      the synapses associated with syntaxin-1-LIR taste cells are from type III cells
      onto nerve processes. These results support the proposition that taste cell
      synapses use classical SNARE machinery such as syntaxin-1 for neurotransmitter
      release in rat circumvallate taste buds.

PMID- 17447253
TI  - Claudin-based permeability barriers in taste buds.
AB  - Tight junctions operate as semipermeable barriers in epithelial tissue,
      separating the apical from the basolateral sides of the cells. Membrane proteins
      of the claudin family represent the major tight junction constituents, and some
      reinforce permeability barriers, whereas others create pores based on solute size
      and ion selectivity. To outline paracellular permeability pathways in gustatory
      tissue, all claudins expressed in mouse taste buds and in human fungiform
      papillae have been characterized. Twelve claudins are expressed in murine taste
      papillae-enriched tissue, and five of those are expressed in human fungiform
      papillae. A subset of the claudins expressed in mouse papillae is uniquely found
      in taste buds. By immunohistochemistry, claudin 4 has been found in mouse taste
      epithelium, with high abundance around the taste pore. Claudin 6 is explicitly
      detected inside the pore, claudin 7 was found at the basolateral side of taste
      cells, and claudin 8 was found around the pore. With the ion permeability
      features of the different claudins, a highly specific permeability pattern for
      paracellular diffusion is apparent, which indicates a peripheral mechanism for
      taste coding.

PMID- 17447254
TI  - In vitro and in vivo binding of neuroactive steroids to the sigma-1 receptor as
      measured with the positron emission tomography radioligand [18F]FPS.
AB  - Sigma-1 receptors are widely expressed in the mammalian brain and also in organs
      of the immune, endocrine and reproductive systems. Based on behavioral and
      pharmacological assessments, sigma-1 receptors are important in memory and
      cognitive processes, and are thought to be involved in specific psychiatric
      illnesses, including schizophrenia, depression, and drug addiction. It is thought
      that specific neuroactive steroids are endogenous ligands for these sites. In
      addition, several sigma-1 receptor binding steroids including progesterone,
      dihydroepiandrosterone (DHEA), and testosterone are being examined clinically for
      specific therapeutic purposes; however, their mechanisms of action have not been
      clearly defined. We previously described the high affinity sigma-1 receptor
      selective PET tracer [(18)F]FPS. This study examines the effect of neuroactive
      steroids on [(18)F]FPS binding in vitro and in vivo. Inhibition constants were
      determined in vitro for progesterone, testosterone, DHEA, estradiol, and estriol
      binding to the [(18)F]FPS labeled receptor. The affinity order (K(i) values) for
      these steroids ranged from 36 nM for progesterone to >10,000 nM for estrodiol and
      estriol. Biodistribution studies revealed that i.v. coadministration of
      progesterone (10 mg/kg), testosterone (20 mg/kg), or DHEA (20 mg/kg)
      significantly decreased [(18)F]FPS uptake (%ID/g) by up to 50% in nearly all of
      eight brain regions examined. [(18)F]FPS uptake in several peripheral organs that
      express sigma-1 receptors (heart, spleen, muscle, lung) was also reduced (54
      85%). These studies clearly demonstrate that exogenously administered steroids
      can occupy sigma-1 receptors in vivo, and that [(18)F]FPS may provide an
      effective tool for monitoring sigma-1 receptor occupancy of specific therapeutic
      steroids during clinical trials.

PMID- 17447255
TI  - 18-MC acts in the medial habenula and interpeduncular nucleus to attenuate
      dopamine sensitization to morphine in the nucleus accumbens.
AB  - 18-Methoxycoronaridine (18-MC), a novel iboga alkaloid congener, is a potential
      treatment for drug addiction. 18-MC has been shown to decrease self
      administration of drugs (e.g., morphine, methamphetamine, nicotine) and attenuate
      opioid withdrawal in rats. In previous studies, systemic pretreatment with 18-MC
      abolished the sensitized increase in accumbens dopamine levels induced by chronic
      morphine administration. In vitro studies have shown that 18-MC is a potent
      antagonist of alpha3beta4 nicotinic receptors, and alpha3beta4 antagonism is
      believed to be the primary mechanism responsible for 18-MC's effects on drug self
      administration and possibly on morphine-induced changes in mesolimbic dopamine.
      While there are very low densities of alpha3beta4 nicotinic receptors in the
      mesolimbic pathway, these receptors are prominently localized in the medial
      habenula (MHb) and in the interpeduncular nucleus (IPN). These nuclei and the
      habenulo-interpeduncular pathway connecting them are believed to function as part
      of an alternate reward pathway modulating the dopaminergic mesolimbic pathway
      known to be involved in drug addiction. In the present study, to determine if 18
      MC acts in the MHb or in the IPN, the effects of local infusion of 18-MC into
      these brain areas were assessed on mesolimbic dopamine responses to acute and
      repeated morphine treatment. Administration of 18-MC (10 mug) into either the IPN
      or MHb blocked the sensitized dopamine response to repeated morphine in the
      nucleus accumbens; 18-MC had no effect on the dopamine response to acute
      morphine. The results suggest that 18-MC acts in the habenulo-interpeduncular
      pathway to modulate the effects of repeated morphine in the dopaminergic
      mesolimbic system.

PMID- 17447256
TI  - Increased dopamine D2High receptors in knockouts of the dopamine transporter and
      the vesicular monoamine transporter may contribute to spontaneous hyperactivity
      and dopamine supersensitivity.

PMID- 17447257
TI  - Antagonist-induced increase in 5-HT1A-receptor expression in adult rat
      hippocampus and cortex.
AB  - Many receptor antagonists function as reverse agonists on the signaling
      transduction pathway, but little is known about the action of these drugs on the
      regulation of receptor expression. Serotonin 1A (5-HT1A) receptor expression in 5
      HT and serum-free fetal hippocampal cultures is increased in the presence of a
      specific 5-HT1A-receptor antagonist N-(2-(4-(2-methoxyphenyl)-1
      piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide (WAY 100635). To study
      the plasticity of postsynaptic 5-HT1A receptors in the presence of antagonist in
      vivo, adult Sprague Dawley rats were injected i.p. either once or twice daily
      with a dose of WAY 100635 (3 mg/kg) over a period of 3 days. The 5-HT1A receptor
      expression was detected by immunocytochemistry and light microscopy, and the
      receptor immunoreactivity (IR) in hippocampus subregions was quantitatively
      assessed by using a comparative computer-assisted morphometric analysis.
      Following the daily injections of WAY 100635, a significant increase in 5-HT1A
      receptor labeling in hippocampal neurons was recorded. This marked increase in 5
      HT1A receptor expression, which occurred within 4 h after a single injection of
      WAY 100635, is evident on the somata membrane and dendritic processes of
      hippocampal and cortex layer V neurons. By contrast, no increase in 5-HT1A
      receptor-IR was observed after multiple daily injections at a low dose (1 mg/kg)
      of WAY 100635. Our study shows that a single or multiple daily injections of WAY
      100635 can result in an increase in 5-HT1A receptor-IR. This increase in labeling
      is consistent with an enhanced expression of the receptor protein. The action of
      this "inverse agonist" may have clinical importance in disorders such as
      depression, epilepsy, and Alzheimer's disease in which 5-HT1A receptor levels are
      deficient.

PMID- 17447258
TI  - Sex differences in the regulation of cocaine and amphetamine-regulated transcript
      expression in hypothalamic nuclei of rats by forced swim stress.
AB  - Cocaine and amphetamine-regulated transcript (CART) peptides are suggested to
      play a role in several physiological processes including feeding, reward,
      neuroendocrine modulation, and the stress response. Although some studies
      implicate the modulation of CART peptide expression by glucocorticoids, direct
      evidence relating CART to the stress response is limited. The present study was
      undertaken to evaluate the possible involvement of CART peptides during acute
      stress in male and female rats. Forced swim was used as the stress procedure.
      Following stress, serum adrenocorticotropic hormone (ACTH), and corticosterone
      (CORT) levels were determined, and CART immunocytochemistry was performed in the
      paraventricular (PVN) and arcuate (ARC) nuclei of the hypothalamus. Our results
      depict the following changes: (1) Serum ACTH and CORT levels were increased by
      stress and CORT levels were higher in female rats than males. (2) Stress
      modulated the number of CART expressing neurons. The degree and direction of this
      modulation varied according to the hypothalamic region and the sex of the
      subject. Forced swim stress increased CART peptide expression significantly in
      the PVN of female rats. In males, although there was a tendency for an increase
      in CART-immunoreactive cells by forced swim stress, the difference was not
      statistically significant. In the ARC nucleus, forced swim stress did not affect
      CART peptide expression in either sex. Our results suggest differential and
      sexually dimorphic modulation of CART expression in the PVN and ARC by forced
      swim stress.

PMID- 17447259
TI  - Elevated dopamine D2High receptors in alpha-1b-adrenoceptor knockout
      supersensitive mice.
AB  - Although amphetamine induces hyperactivity by releasing dopamine (DA), mice that
      lack alpha1b-adrenoceptors do not release DA in response to amphetamine and do
      not, therefore, exhibit locomotor supersensitivity to amphetamine. However, such
      mice reveal hyperlocomotion to p-chloroamphetamine (PCA). Because these alpha1b
      adrenoceptor knockout mice have no alterations in the striatal densities of DA D1
      or D2 receptors, the basis for any possible dopaminergic contribution to the PCA
      induced hyperlocomotion to PCA is unclear. Therefore, because supersensitive
      animals are generally known to have a higher proportion of DA D2 receptors in the
      high-affinity state for DA D2(High), we investigated whether there was any change
      in the alpha1b-adrenoceptor knockout striata in the proportion of DA D2(High)
      receptors to determine whether there could be a DA-based contribution to the PCA
      induced hyperlocomotion. We found that the proportion of D2(High) in the wild
      type striata was 23 +/- 3.3%, whereas that in the alpha1b-adrenoceptor knockout
      striata was 52 +/- 2.9%, an increase of 2.3-fold. This elevation agrees with
      other types of DA-supersensitive animal striata and could assist in eliciting a
      supersensitive response in these alpha1b-adrenoceptor knockout mice.

PMID- 17447261
TI  - Multisensory convergence in auditory cortex, I. Cortical connections of the
      caudal superior temporal plane in macaque monkeys.
AB  - The caudal medial auditory area (CM) has anatomical and physiological features
      consistent with its role as a first-stage (or "belt") auditory association
      cortex. It is also a site of multisensory convergence, with robust somatosensory
      and auditory responses. In this study, we investigated the cerebral cortical
      sources of somatosensory and auditory inputs to CM by injecting retrograde
      tracers in macaque monkeys. A companion paper describes the thalamic connections
      of CM (Hackett et al., J. Comp. Neurol. [this issue]). The likely cortical
      sources of somatosensory input to CM were the adjacent retroinsular cortex (area
      Ri) and granular insula (Ig). In addition, CM had reliable connections with areas
      Tpt and TPO, which are sites of multisensory integration. CM also had topographic
      connections with other auditory areas. As expected, connections with adjacent
      caudal auditory areas were stronger than connections with rostral areas.
      Surprisingly, the connections with the core were concentrated along its medial
      side, suggesting that there may be a medial-lateral division of function within
      the core. Additional injections into caudal lateral auditory area (CL) and Tpt
      showed similar connections with Ri, Ig, and TPO. In contrast to CM injections,
      these lateral injections had inputs from parietal area 7a and had a preferential
      connection with the lateral (gyral) part of Tpt. Taken together, the findings
      indicate that CM may receive somatosensory input from nearby areas along the
      fundus of the lateral sulcus. The differential connections of CM compared with
      adjacent areas provide additional evidence for the functional specialization of
      the individual auditory belt areas.

PMID- 17447262
TI  - Names will often hurt you.

PMID- 17447260
TI  - Measurement of 5-HT1A receptor binding in depressed adults before and after
      antidepressant drug treatment using positron emission tomography and [11C]WAY
      100635.
AB  - OBJECTIVE: To assess effects of chronic antidepressant drug treatment on
      serotonin type-1A receptor (5-HT(1A)R) binding potential (BP) in major depressive
      disorder. METHODS: Depressed subjects (n = 27) were imaged using PET and
      [(11)C]WAY-100635 at baseline and following a median of 9.4 weeks of treatment
      with selective serotonin reuptake inhibitor or dual reuptake inhibitor
      antidepressant agents. Fifteen subjects had complete pre- and post-treatment scan
      data. The 5-HT(1A)R BP was derived from the tissue time-radioactivity
      concentrations from regions-of-interest defined a priori, using a simplified
      reference tissue model (SRTM), and in a subset of subjects, compartmental
      modeling (CMOD). RESULTS: Chronic treatment had no effect on pre- or post
      synaptic 5-HT(1A)R BP, as confirmed by both the SRTM and CMOD analyses. These
      results were unaffected by treatment response status and were consistent across
      brain regions. Among the 22 subjects for whom the clinical response-to-treatment
      was established, the treatment nonresponders (n = 7) had higher baseline BP
      values in the left (P = 0.01) and right orbital cortex (P = 0.02) than the
      responders (n = 15). CONCLUSIONS: Chronic antidepressant drug treatment did not
      significantly change cerebral 5-HT(1A)R binding, consistent with preclinical
      evidence that the alterations in serotonergic function associated with
      antidepressant drug administration are not accompanied by changes in 5-HT(1A)R
      density. Higher baseline 5-HT(1A)R binding was associated with poorer response to
      treatment.

PMID- 17447263
TI  - I know a flu shot is recommended for people over 50, but should I get any other
      vaccines?

PMID- 17447264
TI  - The anatomy of the cerebellar nuclei in the normal and scrambler mouse as
      revealed by the expression of the microtubule-associated protein kinesin light
      chain 3.
AB  - Conventional kinesin is a motor protein complex including two heavy chains and
      two light chains (KLC). Junco et al. (Junco, A., Bhullar, B., Tarnasky, H.A. and
      van der Hoorn, F.A., 2001. Kinesin light-chain KLC3 expression in testis is
      restricted to spermatids. Biol. Reprod. 64, 1320-1330). recently reported the
      isolation of a novel KLC gene, klc3. In the present report, immunohistochemistry
      has been used to characterize the expression of KLC3 in the cerebella of normal
      and scrambler (scm) mutant mice. In cryostat sections through the cerebellum of
      the normal adult mouse immunoperoxidase stained for KLC3, reaction product is
      deposited in the nuclei and somata of deep cerebellar nuclear neurons. No other
      structures are stained in the cerebellum. Strong and specific KLC3 expression is
      observed in the adult cerebellum in all three major cerebellar nuclei--medial,
      interposed, and lateral. Double immunofluorescence studies reveal that KLC3
      immunoreactivity is colocalized with both endosomes and GW bodies. KLC3
      immunohistochemistry has been exploited to study the organization of the
      cerebellar nuclei in scrambler mice, in which disruption of the mdab1 gene
      results in severe foliation defects due to Purkinje cell ectopia, with most
      Purkinje cells clumped in centrally located clusters. Despite the severe failure
      of Purkinje cell migration, the cerebellar nuclei appear normal in scrambler
      mutant mice, suggesting that their topography is dependent neither on normal
      Purkinje cell positioning nor the Reelin signaling pathway.

PMID- 17447265
TI  - Current awareness in human psychopharmacology.

PMID- 17447266
TI  - Abstracts of the 32nd Annual Meeting of the American Society of Andrology, April
      18-24, 2007, Tampa, Florida, USA.

PMID- 17447268
TI  - [Abstracts of the 41st Congress of the French College of Vascular Pathology, 14
      16 March 2007, Paris, France].

PMID- 17447267
TI  - Abstracts of the International Congress on Evidence Based Interventions to
      Prevent Postpartum Hemorrhage: Translating Research into Practice, July 12-15,
      2006, Goa, India.

PMID- 17447270
TI  - Abstracts of the 2007 ECNP Workshop on Neuropsychopharmacology for Young
      Scientists in Europe, Nice, France, 8-11 March 2007.

PMID- 17447269
TI  - Becoming an American company: a holistic approach to decision making.

PMID- 17447271
TI  - Mid-level workers: high-level bungling?

PMID- 17447272
TI  - [Ockelbo disease: stinging fly transmitted polyarthritis in Scandinavia].

PMID- 17447274
TI  - [Abstracts of the 48th Congress of the German Society of Pneumology and
      Artificial Respiration Medicine, 14-17 March 2007, Mannheim].

PMID- 17447273
TI  - Chronic ankle instability and fatigue create proximal joint alterations during
      performance of the Star Excursion Balance Test.
AB  - The combined effects of chronic ankle instability (CAI) and lower extremity
      fatigue on measures of neuromuscular control have not been well established. The
      purpose of this study was to investigate the influence of CAI on the performance
      of a dynamic postural control task, the Star Excursion Balance Test (SEBT), after
      fatiguing activities. Thirty subjects with (n = 14) or without (n = 16)
      unilateral CAI completed anterior, medial, and posterior reaching directions of
      the SEBT performed before and after a lunging fatigue protocol and an open chain
      ankle isokinetic fatigue protocol. Pre-post fatigue change scores were calculated
      for sagittal plane kinematics of the stance leg and the normalized reach
      distances (%MAXD). Using a regression model, group and kinematic data were used
      to explain between subject differences in %MAXD. For each reaching direction, a
      separate analysis was completed for the two fatigue conditions. When reaching
      anteriorly after the lunge fatigue condition, CAI and the changes in knee and hip
      flexion predicted approximately 49 % of the variance in %MAXD (R2 = .487; p =
      .001). When reaching medially under lunge fatigue, CAI predicted approximately 20
      % of the variance in %MAXD (R2 = .198; p = .014). Isolated ankle fatigue did not
      cause significantly different responses between groups. For two of the reaching
      directions, CAI status significantly influenced the variances in %MAXD under the
      influence of lunge fatigue. Functional fatigue protocols

PMID- 17447275
TI  - Effect of massage of the hamstring muscles on selected electromyographic
      characteristics of biceps femoris during sub-maximal isometric contraction.
AB  - The aim of this study was to investigate whether a single massage of the
      hamstring muscles would alter selected electromyographic characteristics of
      biceps femoris during a sub-maximal isometric contraction. Eleven healthy young
      males participated in this crossover study. They were randomly assigned to two
      groups, receiving either a 15-minute hamstring muscle massage or a 15-minute
      prone rest. One week later they returned to receive the alternate intervention.
      Immediately pre- and post-intervention, participants were instructed to contract
      their muscles just sufficiently to maintain right knee flexion (5 degrees from
      full extension) for 30 seconds. Simultaneous to this contraction, surface
      electromyography (EMG) was used to record the electrical activity of right biceps
      femoris. Electromyograms were analyzed by calculating the averaged/integrated EMG
      (aEMG) and median frequency (MF) for each of 14 one-second windows, sampled every
      two seconds throughout the 30-second contractions per participant. Mean values of
      aEMG and MF were calculated per participant (aEMGmean and MFmean), pre- and post
      massage or rest intervention. Group means (n = 11) of aEMGmean and MFmean were
      then calculated and compared using a repeated measures analysis of variance
      (ANOVA) procedure (p < 0.05). Rates of change of aEMG and MF throughout each 30
      second contraction were represented by their respective gradients as functions of
      time. These gradients were similarly compared pre- to post-intervention using
      repeated measures ANOVA (p < 0.05). For the young healthy males considered in
      this study, a single massage of the hamstring muscles had no statistically
      significant effects on selected electromyographic characteristics of biceps
      femoris during sub-maximal isometric contractions (p > 0.05).

PMID- 17447276
TI  - Dopamine agonists and valvular heart disease.

PMID- 17447277
TI  - Dopamine agonists and valvular heart disease.

PMID- 17447279
TI  - Dopamine agonists and valvular heart disease.

PMID- 17447278
TI  - Dopamine agonists and valvular heart disease.

PMID- 17447280
TI  - Impact of Emerging Zoonotic Diseases and Animal Health. Proceedings of the 8th
      Biennial Conference of the Society for Tropical Veterinary Medicine, June 26-July
      1, 2005, Hanoi, Vietnam.

PMID- 17447281
TI  - Persistent coronary occlusion after myocardial infarction.

PMID- 17447282
TI  - Persistent coronary occlusion after myocardial infarction.

PMID- 17447283
TI  - Persistent coronary occlusion after myocardial infarction.

PMID- 17447284
TI  - Persistent coronary occlusion after myocardial infarction.

PMID- 17447285
TI  - Persistent coronary occlusion after myocardial infarction.

PMID- 17447286
TI  - Antibiotic prophylaxis in colorectal surgery.

PMID- 17447287
TI  - International aeromedical evacuation.

PMID- 17447288
TI  - International aeromedical evacuation.

PMID- 17447289
TI  - Selected papers from the Larry Hench Symposium, London, United Kingdom, September
      2005.

PMID- 17447290
TI  - Proceedings of the 2006 Chicago Supportive Oncology Conference.

PMID- 17447291
TI  - Clinical practice guidelines for anxiety disorders.

PMID- 17447292
TI  - DE: Terminated aide filed for workers' comp.: compensation denied--'termination
      for cause'.

PMID- 17447293
TI  - Oral pathology quiz # 54. Case number 3. Fibroma.

PMID- 17447294
TI  - Oral pathology quiz # 54. Case number 4. Odontogenic keratocyst.

PMID- 17447295
TI  - Searching for funding. Docs plead for health IT cash, but action unlikely.

PMID- 17447296
TI  - Epidural analgesia for labour in a patient with neural tube defect.

PMID- 17447297
TI  - Bilateral auscultation with a modified precordial stethoscope.

PMID- 17447298
TI  - Awareness and monitoring of tracheal tube cuff pressure in a multidisciplinary
      intensive care unit.

PMID- 17447299
TI  - Anaesthesia for abdominal aneurysm repair in a patient with Guillain-Barre
      Syndrome.

PMID- 17447300
TI  - Renal failure and neuromuscular weakness in Cleistanthus collinus poisoning.

PMID- 17447301
TI  - Drawing the line.

PMID- 17447302
TI  - Still counting.

PMID- 17447303
TI  - Expertise.

PMID- 17447304
TI  - Face to face.

PMID- 17447305
TI  - Extra-ordinary people.

PMID- 17447306
TI  - Outside the box. Research that tends not to be done in psychiatric services.

PMID- 17447307
TI  - Homes of their own.

PMID- 17447308
TI  - Regulation. Confusion abounds over whistle-blower rules.

PMID- 17447309
TI  - VALUE process helps families cope with end-of-life choices in the intensive care
      unit.

PMID- 17447310
TI  - A growing problem.

PMID- 17447312
TI  - Anti-HIV agents. Leading to lipodystrophy.

PMID- 17447311
TI  - Anti-HIV agents. New drugs, new hope, old lessons.

PMID- 17447313
TI  - Anti-HIV agents. American study finds efavirenz linked to fat wasting.

PMID- 17447314
TI  - Anti-HIV agents. A second study confirms fat loss issues with efavirenz.

PMID- 17447315
TI  - Anti-HIV agents. Efavirenz and fat wasting--what might be happening?

PMID- 17447316
TI  - Anti-HIV agents. Integrase inhibitor raltegravir makes its mark.

PMID- 17447317
TI  - Anti-HIV agents. Raltegravir--other issues.

PMID- 17447318
TI  - What really triggers a heart attack? Doctors are trying to zero in on heart
      attack origins--but prevention, not prediction, remains the prime strategy for
      helping patients.

PMID- 17447319
TI  - Take a load off your heart. More seniors are turning to bariatric surgery to lose
      weight and help cure obesity-related illnesses.

PMID- 17447320
TI  - Rx for success: customize your cardiac workout. Establish an exercise routine to
      help improve your health and reduce risk of future cardiac events.

PMID- 17447321
TI  - Protect your feet and joints while exercising.

PMID- 17447322
TI  - Choosing the right statin for you. All statin drugs are not created equal. Your
      doctor will prescribe the best one to achieve your target LDL level.

PMID- 17447323
TI  - Which heart specialist should you call? Knowing how to navigate the array of
      cardiac specialists can ensure that your quickly get the treatment you need.

PMID- 17447324
TI  - Ask the doctors. I've read that tissue valve replacement is good for only about
      10 years. If true, my time would be up very soon. What can I do to extend the
      life of my valve and myself?

PMID- 17447325
TI  - Dracunculiasis eradication. Global surveillance summary, 2006.

PMID- 17447326
TI  - [The 107th Annual Meeting of the Japan Surgical Society. Osaka, Japan. April 11
      13, 2007. Abstracts].

PMID- 17447327
TI  - An up side to ozone depletion? Striking a balance between the good and bad
      effects of UV.

PMID- 17447328
TI  - Theoretically speaking. David Clary talks molecular quantum dynamics with Hilary
      Crichton.

PMID- 17447329
TI  - Delivering the goods.

PMID- 17447330
TI  - Disease management in fee-for-service Medicaid programs.

PMID- 17447331
TI  - Mental health parity. Interim final amendment to regulation.
AB  - This document contains an interim final amendment to modify the sunset date of
      interim final regulations under the Mental Health Parity Act (MHPA) to be
      consistent with legislation passed during the 109th Congress.

PMID- 17447332
TI  - Optometrists as "acceptable medical sources" to establish a medically
      determinable impairment. Final rules.
AB  - We are revising the Social Security and Supplemental Security Income (SSI)
      disability regulations regarding sources of evidence for establishing a medically
      determinable impairment under titles II and XVI of the Social Security Act (the
      Act). The revised regulations expand the situations in which we consider licensed
      optometrists to be "acceptable medical sources."

PMID- 17447333
TI  - King's conceptual system, theory of goal attainment, and transaction process in
      the 21st century.

PMID- 17447334
TI  - A Neuman systems model perspective on nursing in 2050.

PMID- 17447335
TI  - Update from the future: thinking of theorist Callista Roy.

PMID- 17447337
TI  - Imaging practice in 2050: King's conceptual framework.

PMID- 17447336
TI  - Flying free: the evolving nature of nursing practice guided by the theory of
      health as expanding consciousness.

PMID- 17447338
TI  - [Nuclear medicine and radiation].

PMID- 17447339
TI  - [World Psychiatry Association: Madrid Declaration of ethical principles in
      psychiatric practice].

PMID- 17447340
TI  - [Significance of gastrointestinal antibiotics in gastrointestinal diseases:
      Normix, the non-absorbable antibiotic].

PMID- 17447341
TI  - Dandruff, seborrheic dermatitis, and psoriasis drug products containing coal tar
      and menthol for over-the-counter human use; amendment to the monograph. Final
      rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule amending the final
      monograph (FM) for over-the-counter (OTC) dandruff, seborrheic dermatitis, and
      psoriasis drug products to include the combination of 1.8 percent coal tar
      solution and 1.5 percent menthol in a shampoo drug product to control dandruff.
      FDA did not receive any comments or data in response to its previously proposed
      rule to include this combination. This final rule is part of FDA's ongoing review
      of OTC drug products.

PMID- 17447342
TI  - Characterisation of Staphylococcus haemolyticus isolated from urinary tract
      infections.
AB  - OBJECTIVE: To determine some virulence factors and antimicrobial susceptibilities
      of Staphylococcus haemolyticus from urinary tract infections. DESIGN: This was a
      laboratory based cross sectional study on S. haemolyticus isolates from urinary
      tract infections. SETTING: College of Health Sciences in Harare, Zimbabwe.
      SUBJECTS: People of all ages with urinary tract infections presenting at health
      centres in Harare. MAIN OUTCOMEMEASURES: Prevalence of virulence factors and
      antimicrobial susceptibilities of S. haemolyticus isolates. RESULTS:
      Deoxyribonuclease (DNase) was produced by 91.8%, delta-haemolysin by 75.5% and
      slime by 32.7% of the 49 S. haemolyticus isolates. Less than 10% of the isolates
      produced lipase, alpha haemolysin and protease. All the S. haemolyticus isolates
      were sensitive to vancomycin and 79.6% to clindamycin. Over 70% of the isolates
      were resistant to chloramphenicol, co-trimoxazole, erythromycin, oxacillin,
      ampicillin and penicillin G. Multi-drug resistance to five or more drugs was
      observed in 69.4% of the isolates. Twenty nine of the 37 isolates that produced
      delta-haemolysin showed multi-drug resistance. CONCLUSIONS: The virulence factors
      produced by many S. haemolyticus were DNase and delta-haemolysin. Most of the
      isolates were resistant to many antimicrobial drugs.

PMID- 17447343
TI  - Anti-diabetic activity of Aloe excelsa.
AB  - OBJECTIVE: To investigate the effect of Aloe excelsa powder on diabetes. DESIGN:
      The experiment was carried out in the laboratory on both normal and diabetic
      rats. Diabetes was induced in the rats by using streptozotocin. Thereafter, blood
      samples were taken from both the normal and diabetic rats and the sugar levels
      measured by using the Accutrend Alpha blood glucose monitoring kit. SETTING: The
      experiment was conducted in the laboratory in the Faculty of Medicine at the
      University of Zimbabwe. SUBJECTS: A total of 280 male albino rats weighing 250 g
      on average were used. They were obtained from the Animal House of the Medical
      School at the University of Zimbabwe. MAIN OUTCOME MEASURES: Reduction in sugar
      levels. RESULTS: The Aloe excelsa powder produced a dose-dependent reduction in
      the blood glucose in blood glucose levels. It also compared well with the effect
      of insulin. CONCLUSION: This study shows that Aloe excelsa has significant
      activity on glucose levels in rats and this, therefore, confirms the claims by
      traditional healers that this plant has anti-diabetic effects.

PMID- 17447344
TI  - Perceptions and barriers to cervical cancer screening in a rural district of
      Mutoko, Mashonaland East Province, Zimbabwe.
AB  - In the World Health Organization's (WHO) report on the International Conference
      on Population and Development (ICPD), member states of the African region
      committed themselves to implement the new concept of reproductive health that is
      centred on human needs and development throughout the life cycle. The ICPD's
      programme of action gave a further impetus to reproductive health by recognising
      reproductive and sexual rights as important factors in development. The major
      thrust areas which included cervical cancer screening, were also adopted by the
      World Health Assembly in its resolution WHA 48.10 and the Regional Committee at
      its 44th session in Brazzaville in its resolution AFR/RC44/R11.

PMID- 17447345
TI  - Concomitant sarcoidosis in a patient with tuberculosis: first report of
      association in Africa.
AB  - Sarcoidosis occasionally develops in patients previously treated for
      tuberculosis. Less commonly, tuberculosis develops as an opportunistic infection
      in patients following corticosteroid treatment for sarcoidosis. Rarely do you
      find sarcoidosis and tuberculosis coexisting in the same patient. This report in
      an African, documents the co-existence of both diseases in a patient,
      highlighting this relationship and reviews the literature on the possible
      aetiologic relationship between tuberculosis and sarcoidosis.

PMID- 17447346
TI  - Journal Watch: evidence that Atorvastatin reduces the risk of stroke and
      myocardial infarction in patients with type 2 diabetes, but with no evidence of
      dyslipidaemia.

PMID- 17447347
TI  - Helicobacter pylori.

PMID- 17447348
TI  - Prevalence of Helicobacter pylori in children less than three years of age in
      health facilities in Nairobi Province.
AB  - OBJECTIVES: To determine the prevalence of Helicobacter pylori in children less
      than three years of age and to determine socio-demographic correlates of
      Helicobacter pylori infection in these children. DESIGN: Cross sectional study.
      SETTING: The "well baby clinics", in Nairobi Province. SUBJECTS: Children less
      than three years of age. RESULTS: A total of 195 children were analysed in the
      study. There were 103 (52.8%) males and 92(47.2%) females giving a male to female
      ratio of 1.1:1. The mean age was 17.7 months and the median age was 16 months
      (range 2 weeks to 36 months). H. pylori antigen was found in stool of 89(45.6%)
      of the children. Low socio-economic status, crowding in the homes and poor
      sanitation were associated with H. pylori infection. CONCLUSION: There is a high
      prevalence rate of H. pylori infection in children less than three years as found
      in this study which is in agreement with studies done in other developing
      countries. Family income is associated with H. pylori infection and families with
      low income are at higher predisposition to H. pylori infection when compared to
      families with high income.

PMID- 17447349
TI  - Campylobacter enteritis in Ilorin, Nigeria.
AB  - BACKGROUND: Campylobacterje junilcoli is one of the most commonly identified
      bacterial causes of acute gastroenteritis worldwide. In Nigeria, it has been
      reported in the northern part of the country, extensive work has also been done
      in the south-west leaving behind the middle-belt of the country. OBJECTIVE: To
      determine the role of Campylobacter jejunilcoli as an agent of diarrhoea in the
      middle-belt of Nigeria. DESIGN: A prospective case control study. SETTING:
      University of Ilorin Teaching Hospital (UITH), private hospitals and primary
      health centers all in Ilorin, Nigeria. SUBJECTS: Three hundred and six children
      with diarrhoea and 100 without diarrhoea were randomly selected. MAIN OUTCOME
      MEASURES: Isolation of Campylobacter jejuni/coli from stool samples. Biological
      characteristics of the isolates. RESULTS: Twenty five (8.2%) of the patients and
      none of the controls had the organism. Campylobacter jejuni and C. coli were 56%
      and 44% respectively. All the isolates were susceptible to erythromycin and
      ciprofloxacin. None of the isolates harboured plasmids. CONCLUSION: C. jejunil
      coli is an important diarrhoea agent in our geographic environment, further
      characterisation is desired of these local strains.

PMID- 17447350
TI  - Seroprevalence of hepatitis B markers in pregnant women in Kenya.
AB  - OBJECTIVE: To evaluate hepatitis B serological markers in pregnant women from
      various geographical sites in Kenya. DESIGN: A cross-sectional observational
      study of women attending antenatal clinics. SETTING: The Kenyatta National
      Hospital and eight hospitals from five provinces in Kenya. SUBJECTS: All women in
      their third trimester of pregnancy attending the antenatal clinic over the period
      June 2001 to June 2002. MAIN OUTCOME MEASURES: For each pregnant woman age and
      gestation were documented. Hepatitis serological markers were evaluated. RESULTS:
      A total of 2241 pregnant women were enrolled. Among them 205 women (9.3%) were
      positive for HbsAg and from these 18 (8.8%) were found to have HbeAg. Protective
      antibodies (anti-HbsAg) were detected in 669 (30.2%) of the women. There were
      notable significant regional differences for HbsAg rates. CONCLUSIONS: These
      results confirm the presence of high disease carrier rate and the corresponding
      previously reported low level of HbeAg suggesting questionable low rate of
      perinatal transmission but high rate of horizontal transmission.

PMID- 17447351
TI  - Pattern of alcohol consumption among commercial road transport workers in a semi
      urban community in south western Nigeria.
AB  - OBJECTIVES: To determine prevalence and pattern of alcohol use, evaluate the
      level of awareness of the harmful consequences of drinking, and determine the
      relationship between alcohol use and some selected factors among commercial road
      transport workers. DESIGN: Cross-sectional survey. SETTING: All the five motor
      parks spread over Ile-Ife, a semi-urban community in south western Nigeria.
      RESULTS: out of the 403 transport workers, 400 (99.3%) agreed to participate in
      the study. The questionnaire of one respondent was rejected. The current
      prevalence rate of alcohol use was 67.2%. Forty seven percent were 'heavy' users;
      15.3% 'moderate' users and 37.7% were occasional or 'mild' users. All the users
      were engaged in the use of commonly available alcoholic beverages in the vicinity
      of the motor parks. Majority of the respondents (74.5%) reported drinking after
      work; 13.5% in the mornings; 10.1% when off-duty and 1.9%, during work.
      Frustrations that are associated with their work topped the list of reasons
      adduced for drinking. Belonging to lower age groups was significantly associated
      with current drinking (chi2 = 17.46, df = 3, p < 0.001). The proportions of
      respondents with unsatisfactory level of awareness regarding the association of
      current drinking with road traffic accidents, and with physical complications
      were high. CONCLUSION: Current alcohol use and use in a hazardous manner is an
      important public health problem among commercial road transport workers in
      Nigeria. There is an urgent need to modify existing legislations or enact new
      laws on 'driving under the influence' of alcohol, and enforce them.

PMID- 17447352
TI  - Drug use and its association with deviant behaviour among rural adolescent
      students in South Africa.
AB  - OBJECTIVE: To examine prevalence of drug use in adolescent students in a rural
      South African community, and to measure the association between drug taking and
      deviant behaviour. DESIGN: Cross-sectional survey using self-administered
      questionnaires. SETTING: Seven middle and secondary schools in Moretele District,
      Mpumalanga Province, South Africa. SUBJECTS: A random sample of 357 rural
      students comprising 193 (54.1%) females and 164 (45.9%) males, aged 11.7 to 19.9
      years (mean age = 15.8; SD = 21.99). MAIN OUTCOME MEASURES: Self-reported use of
      drugs. The prevalence of bullying, absenteeism and weapon-carrying among
      respondents who had used substances was determined. RESULTS: Responses were
      obtained from 357 Grade 7-12 students. Alcohol was the most commonly used drug by
      the respondents. Reported lifetime prevalence of alcohol use was 47.9% (95% CI:
      42.6-53.2%); tobacco, 18.2% (95% CI: 14.4-22.7%), inhalants, 5.9% (95% CI: 3.8
      9.0%); cannabis 5.6% (95% CI: 3.5-8.7%). Reported use of mandrax (3.9%),
      tranquillizer (3.6%) and cocaine (1.4%) was low. Multivariate logistic regression
      analysis showed that being male (adjusted odds ratio [AOR] = 2.21; 95% confidence
      interval [CI]: 1.33-3.36; p = 0.002), initiating alcohol use before the age of 13
      years (AOR: 2.25; 95% CI: 1.15-4.40; p = 0.018) and alcohol use were associated
      with absenteeism. Alcohol use, irrespective of the duration and being a male
      (AOR: 3.51; 95% CI: 1.50-8.20) was associated with bullying. The significant
      factors associated with weapon carrying were alcohol, male sex and initiating
      alcohol use before 13 years of age. CONCLUSION: Drug use, particularly alcohol is
      common among adolescent students, especially males. There is also a positive
      association between drug use and undertaking precarious behaviour.

PMID- 17447353
TI  - Mothers' knowledge on malaria and vector management strategies in Nyamira
      District, Kenya.
AB  - BACKGROUND: Maternal knowledge on malaria and vector control measures are
      important because they enable mothers make an informed choice on the method of
      malaria control to use for their children under five years. OBJECTIVE: To
      determine the mothers' knowledge on malaria and vector control measures
      particularly use of insecticide treated nets. DESIGN: Cross sectional,
      descriptive study. SETTING: Eight health centres in Nyamira District, Kenya.
      SUBJECTS: Four hundred mothers bringing their children aged five years and below
      to the child health clinics. RESULTS: Mothers had a problem of defining malaria.
      Majority of them (91.8%) recognised mosquitoes as causing malaria. About 30%
      associated malaria with dirt, dirty compounds, dirty food/utensils, unboiled
      water and uncooked food. Many mothers identified basic malaria symptoms such as
      headache (70%), fever (68.8%), cold (65%), body or joint pain (65.5%) and
      abdominal pain/ vomiting (0.5%). Mothers (40.8%)were less knowledgeable on most
      vulnerable groups to malaria. A large number of mothers (55.5%) used nothing to
      protect themselves and their children under five years from mosquito bites. The
      radio (69%) tuned in the local language, played a very important role in the
      mothers' knowledge about the use of mosquito nets and insecticide treated nets.
      CONCLUSION: By virtue of the fact that majority of mothers (91.8%) recognised
      that mosquitoes caused malaria, it was an indicator that they were knowledgeable
      of its existence. Mothers were also informed of most of the malaria vector
      control measures particularly use of bed nets and insecticide treated nets.
      However, the general usage of those measures was very low.

PMID- 17447354
TI  - Cervicothoracic arachnoid cyst in a patient with neurofibromatosis: case report.
AB  - Intradural cervicothoracic arachnoid cysts are not common. They may be
      congenital, or secondary to trauma, surgery, haemorrhage, or inflammation. This
      is a report of a 39-year-old man who presented with cutaneous neurofibromatosis
      and cervicothoracic arachnoid cyst causing gradual quadriparesis. Magnetic
      resonance imaging showed an intradural extramedullary anterior cystic lesion at
      C5-T2 level. Laminectomy and mersupialisation of the cyst was performed.
      Histology confirmed the diagnosis of arachnoid cyst. The patient recovered
      without neurological deficit.

PMID- 17447355
TI  - Does finding a congenital heart disease in children with stroke always indicate a
      causative relationship?

PMID- 17447356
TI  - A review of 3 Hz spike and wave complexes in EEGs done at Kenyatta National
      Hospital, Nairobi, Kenya.

PMID- 17447357
TI  - Sustainability of community based family planning services: experience from rural
      Ethiopia.
AB  - The important role of active Community Based Reproductive Health Services
      (CBRHS), formerly known us Community Based Distribution (CBD) of family planning
      program, in increasing contraceptive uptake has been reported from several
      studies. However, the sustainability of project based services has not been
      documented in Ethiopia. This study was conducted to assess the effectiveness and
      sustainability of community based Family planning services in rural communities
      of Ethiopia. The study was carried out in three sets of 30 peasant villages
      selected from five districts of Eastern Showa Zone in Ethiopia. Comparison was
      made between never former; and current CBRHS areas. Relevant information was
      collected using a structured and pre-tested questionnaire. The respondents were
      women in the reproductive age groups (15-49 years). Knowledge about contraception
      was higher in both former and current CBRHS communities as compared to never
      CBRHS areas [MH-OR (95% CI) = 6.89 (4.69, 10.17) and 12.48 (7.84, 20.25)],
      respectively. Ever use of modern contraception was significantly greater among
      women from former and current CBRHS communities as compared to never CBRHS
      communities [MH-OR (95% CI) = 3.75 (2.54, 5.97) and 5.72 (3.93, 9.39),
      respectively]. Current use of modern contraception methods was however
      significantly better only in current CBRHS areas [MH-OR (95% CI) = 2.42; (1.16,
      5.37)]; there was no statistically significant difference with former CBRHS areas
      [MH-OR (95% CI) = 1.13; (0.51, 2.49)]. Results of this study indicate that the
      effect of CBRHS in raising the level of modern contraception use in rural
      communities is transient. In order to sustain the effects of a good community
      based family planning services appropriate mechanisms must be designed to
      motivate and enable women to continuously utilize the services.

PMID- 17447358
TI  - Chldren's rights and corporal punishment in Assendabo town and the surrounding
      area, South West Ethiopia.
AB  - Corporal punishment of children has been used as a disciplinary measure to modify
      undesirable behavior of children worldwide. This study was conducted with the aim
      of determining the knowledge, attitudes and the extent that corporal punishment
      is practiced in the study area. A cross-sectional study was conducted among the
      residents of Assendabo town and its surroundings area form January 8-12, 2003. A
      total of 368 residents with at least one child living with them were selected and
      interviewed using a structured questionnaire. Data were analyzed using SPSS for
      windows version 11.0. The study revealed 310 (87.6%) of the parents employed
      child corporal punishment as a method of disciplining out of which nearly half of
      them claimed their action was for the ultimate benefit of their children. Only 12
      (3.5%) of the parents reported infliction of trauma while punishing their
      children. There was no significant parental difference both in attitude and
      practice of child corporal punishment. Family income is found to affect both
      attitude and practice of corporal punishment. From this study it is concluded
      that the knowledge about the existence of a legal framework which protects a
      child from any form of abuse is low. The attitude towards avoidance of child
      corporal punishment is unfavorable and there is a high prevalence of child
      corporal punishment practiced.

PMID- 17447359
TI  - Prevalence and clinical correlates of the hypertensive disorders of pregnancy at
      Tikur Anbessa Hospital, Addis Ababa, Ethiopia.
AB  - A one-year longitudinal study was conducted at Tikur Anbessa central referral
      Hospital to assess the prevalence of hypertensive disorders of pregnancy (HDP),
      to see the socio-demographic and clinical parameters and pregnancy outcome of
      pregnancies afflicted by these complications. Out of 3424 deliveries conducted
      during the study period, 183 (5.3%) mothers were found to have one form of
      hypertensive disorders of pregnancy, 85.2% were cases of pregnancy induced
      hypertension (PIH),the majority (78.2%) were severe pre eclampsia and eclampsia;
      the remaining 14.8% had pregnancy aggravated hypertension (PAH) or chronic
      hypertension. Preterm delivery rate was 48.6% for all cases of HDP. Intervention
      rate was high with 44.3% induction of labor and 44.3% caesarian section, which is
      much higher than the over all intervention rate in the hospital's obstetric
      population during the studied period. Prenatal mortality rate (PNMR), case
      fatality rate (CFR) and intra uterine growth restriction (IUGR) were 300/1000
      deliveries, 27/1000 deliveries and 41.6% respectively in mothers with HDP. Severe
      hypertension, high urine protein and high uric acid level were found to be
      associated with higher CFR, and poor prenatal outcome. The study provides base
      line data on HDP in a hospital obstetric population in Ethiopia. Important
      peculiar findings in this study were a very high rate of severe disease, PNMR and
      CFR compared to other institutional studies. There is a need to conduct nation
      wide multi center study on HDP in order to have national base line data on this
      important pregnancy complication.

PMID- 17447360
TI  - Eclampsia a 5 years retrospective review of 216 cases managed in two teaching
      hospitals in Addis Ababa.
AB  - OBJECTIVE: to measure the magnitude of eclampsia and its maternal and perinatal
      outcome. METHODS: A 5 years retrospective descriptive study was conducted on 216
      eclamptic cases diagnosed, admitted and managed from October 1994 to September
      1999 in the two teaching hospitals of Addis Ababa; namely Tikur Anbessa and St
      Paul's Hospitals. RESULTS: There were 257 mothers with eclampsia treated in the
      given period and 35741 deliveries making the incidence of eclampsia 7.1/1000
      deliveries. Eighty-four women (38.9%) had any antenatal care, 157 (72.7%) were
      nulli-parous and 69 (31.8%) were aged below 20. Convulsion occurred ante-partum
      in 133 (61.6%), intrapartum in 49 (22.7%) and postpartum in 34 (15.7%) mothers.
      The most frequently sited symptoms before convulsion include headache in 83.8%,
      visual disturbance in 41.6% and epigastric pain in 38.4% of the cases. Ninety
      nine (45.8%) women were delivered by cesarean section making the cesarean section
      rate among eclamptic mothers significantly higher than the rate among the general
      population, which was 16.6% at the same period. (P = 0.0001). The multiple
      pregnancy rate was 5.7%, which was significantly higher than the rate among the
      general population of 1.5% at the same time. Seventy-four mothers had repeated
      convulsion after admission to the hospitals and initiation of the standard
      treatment. Twenty-eight mothers with eclampsia died making the case fatality rate
      13%. Seven mothers (3.2%) died before delivery. Forty-four Stillbirths and twenty
      five early neonatal deaths occurred making the perinatal mortality rate
      312.2/1000 deliveries. CONCLUSION: Eclampsia is a common complication still
      associated with high level of maternal and perinatal mortality as well as
      morbidity. ANC coverage should be strengthened to detect preclampsia, and prevent
      eclampsia. Management in the hospital should be optimized to prevent recurrent
      convulsions and complications after admission.

PMID- 17447361
TI  - Pattern of admissions to the medical intensive care unit of Addis Ababa
      University Teaching Hospital.
AB  - A case-series study of all admissions using patient registers was carried out to
      analyse patterns of medical admissions into the Medical Intensive Care Unit
      (MICU) of the Addis Ababa University Teaching Hospital, and evaluate for any
      changes in that pattern over a study period. All patients admitted to the MICU of
      a 500-bed Teaching Hospital in Addis Ababa between 1985-2000 were the study
      subjects. Demographic variables, specific categories of diagnoses and their
      outcomes were recorded A total of 3548 patients (male to female ratio of 1.4:1,
      mean age 37.10 +/- 17.29) were admitted from September 1985 to August 2000. Acute
      infectious and cardiovascular diseases accounted for half of the entire critical
      care admissions with infectious diseases accounting for 30%. Among specific
      diagnoses, diabetic ketoacidosis was the leading cause of admission followed by
      acute myocardial infarction and severe and complicated malaria, each accounting
      for 10.7, 9.8 and 9.3% of all admissions respectively. Trends of admissions over
      the sixteen-year period showed steady increase in relative frequency of acute
      complications of non-communicable diseases consisting of diabetes, acute
      myocardial infarction and stroke while infectious diseases showed interspersed
      peaks of admissions coinciding with epidemics. The overall mortality of the MICU
      was 32%, with proportionally more female deaths, 34.8 versus 29% (P = 0.0002).
      Severe and complicated malaria was the leading cause of death (10.3%) followed by
      tetanus (6.4%) and acute myocardial infarction (6.3%). The increase in relative
      and absolute frequency of acute complications of non-communicable diseases most
      probably heralds an emerging epidemic of non-communicable diseases related to
      life style changes in the urban well to do in addition to existing problems of
      infectious diseases of poverty.

PMID- 17447362
TI  - The prospect of dental fluorosis prevention in Wonji Ethiopia.
AB  - This study identified factors that are associated with dental fluorosis among
      school adolescents in an endemic area using a control design. Data were collected
      using a directed self-administered questionnaire. Dental fluorosis was confirmed
      by a dentist. Out of the 472 students who participated in the study, 398 had
      dental fluorosis and the remaining 74 were free of dental fluorosis. A logistic
      regression analysis revealed children born in Wonji compared to those born
      elsewhere [Adjusted OR (95% CI): 5.12 (2.68, 9.75)]; males compared to female
      [Adjusted OR (95% CI): 2.76 (1.52, 5.00)]; and those who obtained their regular
      drinking water from pipe distribution compared to those who obtained water from
      other sources [Adjusted OR (95% CI): 3.5 (1.24, 10.02] were more likely to have
      dental fluorosis. Students in the age group 13-14 year compared to those in 11-12
      year were less likely to have dental fluorosis [Adjusted OR (95% CI): 0.43 (0.25,
      0.76)]. The findings indicate that the risk of dental fluorosis is still much
      higher for the population in Wonji and recommend strengthening appropriate
      intervention systems at household and community levels.

PMID- 17447363
TI  - Gallstone disease in a teaching hospital, Addis Ababa: a 5-year review.
AB  - There are not many studies of gallbladder disease in Africa. The disease appears
      to be not uncommon in Ethiopia. To determine the prevalence and evaluate the
      management of gallstone disease in a central teaching hospital, a 5-year
      retrospective study was undertaken in 747 patients surgically treated for
      gallbladder disease in the period 1995-99 in Tikur Anbessa Hospital, Addis Ababa.
      The sex ratio (M:F) was 1:5, narrower ratio in complicated cholelithiasis. The
      mean age was 42 years. About 80% of patients were in the age group between 30 and
      60 years. The median duration of symptoms at admission was 2 years. Abdominal
      pain, in 96% of cases situated in the right upper quadrant (RUQ) and usually
      aching type, was the most frequent presenting symptom; RUQ tenderness was the
      most common sign. Clinically, 29.4% of patients were categorized obese. Gallstone
      detection rate by ultrasound was about 96% but cholecystitis appeared to be
      overlooked. At operation, about 77% of cases had features of chronic
      cholecystitis, 2% acalculous cholecystitis. Majority of the stones were grossly
      cholesterol stones. Cholecystectomy was performed in 99% of cases, most often
      through the oblique subcostal and transverse routes. The overall in-hospital
      mortality rate was 0.4%. Nearly 87% of cases had postoperative course without
      incident. The etiologic factors and the type of gallstones, we believe, are not
      different from that of the developed world. Cholecystectomy is a safe and most
      effective procedure that provides ultimate cure for symptomatic gallstone
      disease.

PMID- 17447364
TI  - Audit of exracapsular cataract extraction with posterior chamber intraocular lens
      implantation in a tertiary eye care center in Ethiopia.
AB  - A retrospective audit of records of 370 eyes of 315 patients for whom
      extracapsular cataract extraction with posterior chamber intraocular lens
      implantation (ECCE-PC IOL) was performed between 1998 and 1999 was made to
      determine postoperative visual outcome and complications. One hundred and ninety
      three patients were males and one hundred and seventy seven were females making a
      male to female ratio of 1:0.9. At two months postoperatively 82 (30.4%) of eyes
      had uncorrected visual acuity of 6/18 or better; while 176 (53.7%) of eyes
      attained an uncorrected visual acuity between 6/18 and 6/60, and 31 (11.5%) had
      visual acuity between 3/60 and 6/60. 340 of 358 (94.9%) had a preoperative visual
      acuity of < 3/60. As a result of the surgery, the percentage of blind eyes
      dropped from 94.9% to 4.4%. The commonest intra operative and early postoperative
      complications encountered were posterior capsular tear with vitreous loss (5.7%)
      and striate keratopathy (11.1%) respectively. Posterior capsular opacity was
      documented in 17 (4.6%) eyes as a late postoperative complication. Routine
      biometry, to calculate Intra ocular Lens (IOL) power was not done and this was
      the major limitation of the study. In conclusion, the study increases awareness
      of cataract surgery outcomes and provides a feedback to achieve better results
      both in terms of quality and quantity in cataract surgery. Further study with
      biometric measurement is recommended.

PMID- 17447365
TI  - The role of ultrasound in diagnosing acute appendicictis.
AB  - Most patients with acute appendicitis present with typical clinical features, and
      diagnosis was traditionally based on clinical data. But the clinical diagnosis is
      not always straightforward, since 30-45% of patients have atypical clinical
      presentation. Recent reports indicate ultrasound is accurate test for diagnosis
      of appendicitis. Thus, the objective of this study was to assess the sensitivity,
      specificity and accuracy of graded compression ultrasound in the diagnosis of
      appendicitis in our setup. A total of 194 patients with suspected appendicitis,
      who have visited the Tikur Anbessa Hospital from July 2002-November 2003, were
      prospectively evaluated with graded compression ultrasound The outcome of 147
      patients was known, of which 58 were operated and 89 were clinically followed.
      The sensitivity of US in diagnosing acute appendicitis was found to be 87.9% with
      specificity of 86.5%. The positive and negative predictive values were 80.9% and
      91.7%, respectively, with accuracy of 87.1%. The criteria for diagnosing
      appendicitis by US were consistent. US also help to give an alternative
      diagnosis, which can mimic appendicitis. Twenty-nine (27.4%) alternative
      diagnoses were made at US. Based on our findings, we recommend that US can be
      used as imaging modality of choice in investigating appendicitis, especially in
      patients with atypical presentation.

PMID- 17447366
TI  - Snake bite envenomation at Aysha refugee camp health center.
AB  - Snake bite remains one of the major public health problems in many countries
      including Ethiopia. This case report comprises four snake bite envenomation
      incidents presented to Aysha refugee camp health center in the eastern part of
      the country between May and August 1999 (hottest season of the year). All the
      four this cases had systemic manifestations one of whom died at arrival, the rest
      being successfully treated and discharged. In the body of the report, each case
      is described, relevant literature reviewed briefly, discussed, and finally
      conclusions are made.

PMID- 17447367
TI  - Hirschsprung's disease and imperforate anus in a new born: unusual assocation.
AB  - The association of congenital aganglionic megacolon and imperforate anus is rare.
      Our patient was a male neonate who initially presented with intestinal
      obstruction due to imperforate anus without fistula. Intraoperative findings and
      colonic biopsy revealed the presence of concurrent Hirschsprung's disease (HD). A
      suspicision that these two disorders may coexist is mandatory for early correct
      diagnosis.

PMID- 17447368
TI  - Clinico-pathologic conference: Tikur Anbessa Hospital, Addis Ababa.

PMID- 17447369
TI  - Update on gastrointestinal stromal tumor [GIST].

PMID- 17447370
TI  - Maternal and child health in Ethiopia: challenges in the AIDS era.

PMID- 17447371
TI  - Survey of protective behaviour practiced against HIV/AIDS in adult TB patients at
      Almata Zonal Hospital.
AB  - OBJECTIVES: To assess the level of protective behaviour against the spread of HIV
      infection and TB transmission in a health facility setting. PATIENTS AND METHODS:
      A cross-sectional study involving 190 adult TB patients on anti-TB treatment was
      conducted at Alamata Zonal hospital, Southern Tigray, in September 2001. RESULTS:
      The study showed that among the study population 83% knew TB is a communicable
      disease, 124 (65.2%) correctly knew the mode of its transmission but only 26
      (16.6%) practiced the appropriate preventive measures. Of the study population 99
      (52%) had previous history of sexually transmitted diseases (STDs), and 120 (63%)
      had multiple sexual partners among whom 94 (78%) had not used condom because 34
      (39%) did not know the role of condom. Similarly, 64 (34%) were not volunteer to
      use condom, and 25 (13%) did not know what condom is, in spite of the fact that
      181 (95%) have heard of HIV/AIDS and 169 (89%) knew unprotected sex as its usual
      route of transmission. One hundred sixty nine (89%) knew that HIV is preventable
      and the perceived preventive measures were mainly 1:1 sexual partner in 140 (74%)
      and use of condom in 98 (52%) whereas 14 (7%) had no idea about HIV prevention
      methods. The majority, 167 (88%) considered HIV a real national problem.
      CONCLUSION: The study population's level of protective behaviour against HIV and
      TB transmission is very low. Measures need to be taken to ensure 100% condom
      availability. Massive campaigns are required to make condom use socially
      acceptable. Health education on prevention of HIV and TB transmission should be
      strengthened to achieve an acceptable level of protective behaviour against these
      diseases.

PMID- 17447372
TI  - Central nervous system toxoplasmosis in adult Ethiopians.
AB  - OBJECTIVES: Toxoplasmosis is identified as one of the major central nervous
      system (CNS) opportunistic infections in AIDS patients. Sero-epidemiological
      surveys done among Ethiopian patients indicated a very high prevalence rate. This
      study was conducted to describe the clinical course of the disease in Ethiopians
      with AIDS. PATIENTS AND METHODS: Three hundred and twenty three patients with
      AIDS and CNS Toxoplasmosis that were consecutively admitted and treated with
      Sulfadoxine Pyrimethamine (SP) at the Tikur Anbessa Specialized Referral Hospital
      were reviewed. The diagnosis CNS Toxoplasmosis was made based on clinical
      features or neuroradiologic findings and response to treatment. In over 80% of
      the cases the dose of Pyrimethamine used was 100 mgs for two days and then 25 mgs
      daily PO. RESULTS: The male to female ratio was one to one. The median age was 34
      years (range 18 - 75). The most common presenting symptoms were headache 293
      (91%), fever 269 (83%), and abnormal level of consciousness in 201 (62%) of the
      cases. Focal neuralgic deficits were seen in 203 (63%) of the cases. The
      diagnosis of CNS toxoplasmosis was based on clinical features and response to
      treatment in 186 (58%) of the cases and on CT scan findings and clinical response
      in 54 (17%) of the cases. Among the 248 (78%) of the cases that had responded
      favorably to SP, 53% had improvement on the 7th day, while the rest had
      improvement on the 14th day of treatment. Major treatment related adverse
      reactions, which required changing treatment, were seen in 68 (20%) of the cases.
      Among patients who survived the first episode of toxoplasmosis, the median follow
      up was for 29 days (range 15-1800). CONCLUSION: Toxoplasmosis had been the most
      AIDS defining event in the study group and clinical response to empiric treatment
      was essentially diagnostic. In our study group the outcome seen with SP as
      compared to the standard recommended treatment yielded comparable results.
      Tolerance to treatment was better and the adverse effects warranting change in
      treatment were fewer despite that only few patients received folinic acid
      supplements. We recommend a well-designed prospective study to establish the
      efficacy and optimal dose of SP in the treatment of CNS toxoplasmosis.

PMID- 17447373
TI  - Does chronic hepatitis B increase Staphylococcus nasal carriage?
AB  - OBJECTIVES: To determine the prevalence of Staphylococcus aureus nasal carriage
      in patients with chronic hepatitis B virus infection. PATIENTS AND METHODS: The
      prevalence of S. aureus nasal carriage was determined in patients with chronic
      hepatitis B virus infection and compared with the prevalence of S. aureus nasal
      carriage among control patients. RESULTS: Between February 2003 and November
      2004, 70 chronic hepatitis B patients and 70 control patients were enrolled in
      the study. S. aureus nasal carriage was shown in 15 (12%) of the patients with
      chronic hepatitis B and 13 (19%) of the control group (P > 0.05). There was no
      difference in nasal colonization between the cases and controls when analysed by
      age, sex, frequency of skin infection, prior use of antibiotics and hospital
      admission in the preceding six months. CONCLUSION: The results of our study show
      that chronic hepatitis B virus infection is not associated with S. aureus nasal
      carriage.

PMID- 17447374
TI  - Pattern and multiple drug resistance of bacterial pathogens isolated from wound
      infection at University of Gondar Teaching Hospital, Northwest Ethiopia.
AB  - OBJECTIVES: Antibiotics resistance among bacteria is a worldwide problem. The
      situation in developing countries like Ethiopia is particularly serious. Since
      the presence of drug resistant bacteria in the environment are threat for public
      health, up-to-date information on local pathogens and drug sensitivity pattern is
      very crucial to treat patients. The aim of this study is to assess the pattern of
      bacterial pathogens from wound infection and their susceptibility to common
      antibiotics. MATERIALS AND METHODS: This laboratory based retrospective study of
      151 wound swabs and sensitivity tests was conducted in Bacteriology Laboratory of
      the University of Gondar Teaching Hospital. The samples were collected and
      processed following standard microbiological techniques as part of the routine
      clinical management of the patient. Antibiotic sensitivity testing was done on
      pure culture isolates employing disc-diffusion method for the commonly used
      antibiotics. RESULTS: Bacterial pathogens were isolated from 79 patients showing
      an isolation rate of 52%. Staphylococcus aureus was the predominant species 65%
      (51/79) followed by Escherichia coli, 8/79 (10%), Klebsiella pneumoniae 9%
      (7/79), Proteus species 4% (3/79) and Streptococci species 4% (3/7). Among Gram
      positive bacteria, S. aureus showed high level of drug resistance against
      penicillin 59% (30/51), tetracycline 57% (29/51), ampicillin 55% (28/51) and co
      trimoxazole 35% (18/51). E. coli was found to be resistant to ampicillin in 87%
      (7/8), tetracycline also in 87% (7/8) and co-trimoxazole 63% (5/8). The over all
      multiple drug resistance patterns were found to be 78.5%. CONCLUSIONS: The
      frequency of single as well as multiple drug resistance is alarmingly high. This
      might be a reflection of inappropriate use of antimicrobials, lack of diagnostic
      laboratory services or unavailability of guideline regarding the selection of
      drugs. Thus, rational use of drugs should be practiced.

PMID- 17447375
TI  - Therapeutic efficacy of sulfadoxin/pyrimethamine in the treatment of
      uncomplicated Plasmodium falciparum malaria in Enseno, Meskan Woreda, Gurage
      zone, SNNPR, Ethiopia.
AB  - OBJECTIVES: To study the the response of Plasmodium falciparum to sulfadoxine
      pyrimethamine (SP). PATIENTS AND METHODS: A cross sectional survey was conducted
      between October and November 2002 to study the response of P. falciparum to the
      standard regimen of sulfadoxine-pyrimethamine (SP)--25 mg/kg of sulfadoxine and
      1.25 mg/kg of pyrimethamin--in 70 patients (35 males, 35 females) who were seen
      Enseno malaria center. Gurage Zone, Sothern Nations, Nationalities, and Peoples
      Region (SNNPR), Ethiopia. The clinical and parasitological responses were studied
      until day-14 in accordance with the modified 1999 WHO in-vivo protocol for the
      evaluation of therapeutic efficacy of anti-malarial drugs. RESULTS: Of 75
      enrolled patients, 5 were lost to follow-up or excluded before day-14. A total of
      70 patients were followed till the end of the study, among which 10 (14.3%) had
      treatment failure. This was noted more in children than in adults and this
      differenrce was statistically significant (OR = 0.14; 95% CI = 1.00, 0.025; P <
      0.05 Fisher's exact test). Clinical presentation with high-grade fever on day-0
      was found to be more predictive for treatment failure (P = 0.0005, Fisher's exact
      test). CONCLUSION: The treatment failure of SP in this study lies between 6-15%
      (14.3%), which is called an Alert period, using an arbitrary cut off point for
      treatment failure. So, it should be supplemented with large-scale sensitivity
      studies to initiate the mechanism for the process of change and assessment of
      possible alternatives.

PMID- 17447376
TI  - The antibiotic prescribing behaviourof physicians for acute tonsillopharyngitis
      in primary care.
AB  - OBJECTIVES: Acute tonsillopharyngitis is one of the most common reasons for
      antibiotic use although it is mostly viral. There seems to be a large variation
      between physicians in prescribing antibiotics. The aim of this study was to
      explore the antibiotic prescribing behaviour of physicians while treating cases
      with acute tonsillopharyngitis. PATIENTS AND METHODS: Data were collected using a
      questionnaire designed to investigate the effect of the antibiotics actively
      promoted by pharmaceutical companies, the sociodemographic details of primary
      care physicians, the geographic location (urban-rural) of the primary care
      organizations, and the effect of laboratory investigations on provider antibiotic
      prescribing behaviour in the treatment of acute tonsillopharyngitis. Sixty six
      primary care organisations (PCOs) and 316 primary care physicians working in the
      66 PCOs in Adana in 2001 were involved in the study. RESULTS: Out of 66 PCOs, 55
      (83%) were urban and 11 (16%) were rural. The response rate was 79%. There was
      significant association between antibiotic prescription for acute
      tonsillopharyngitis and geographic location, antibiotic promotion by
      pharmaceutical companies and postgraduate training for physicians (p = 0.001, p =
      0.0001, p = 0.0001, respectively). There was also significant association between
      laboratory investigation and geographic location, postgraduate training for
      physicians, and period since graduation (p = 0.0001, p = 0.0001, p = 0.003,
      respectively). CONCLUSIONS: Antibiotics in cases with acute tonsillopharygitis
      are more frequently prescribed in rural areas and in PCOs where the visits and
      motivation from pharmaceutical companies are intensive. Physicians without
      postgraduate vocational training prescribe more antibiotics for cases with acute
      tonsillopharyngitis.

PMID- 17447377
TI  - Assessment of the dispensing practices of drug retail outlets in selected towns,
      north west Ethiopia.
AB  - OBJECTIVES: Ethical dispensing of drugs and medicinal products is an integral
      component of rational drug therapy. Nevertheless, this essential health issue
      apparently has a large commercial aspect. This study was conducted to assess the
      dispensing practices of pharmacies and rural drug vendor shops in selected towns
      of northwest Ethiopia. MATERIALS AND METHODS: In this cross-sectional study, all
      private pharmacies (totally 3) and rural drug vendor shops (totally 9) were
      included in the study. The dispensing activities, condition of the dispensing
      environment, dispensed drugs and other relevant information were recorded on a
      structured protocol. In total, the dispensing procedures for 74 clients in
      pharmacies and 194 clients in rural drug vendor shops were observed (each premise
      was visited only once). RESULTS: The results demonstrated that all premises
      possessed clean dispensing environment. The average dispensing time was 1,86
      minutes in Pharmacies and 1.7 minutes in rural drug vendor shops. The dispensing
      of prescription-only medications without a medical prescription was higher in
      rural drug vendor shops (68.8%) than in Pharmacies (7.3%). The provision of
      verbal (about 87%) and written (about 66%) instructions was similar in both
      pharmacies and rural drug vendor shops. CONCLUSION: The dispensing environment
      and storage conditions are satisfactory. However, the dispensing of prescription
      only-medications without medical prescription was more frequent particularly in
      rural drug vendor shops. The provision of drug-related information especially
      labeling of the dispensed medications was not satisfactory in both types of drug
      retail outlets. Implementation of training programs and supervisory visits are
      recommended for the improvement of dispensing practices and application of code
      of Ethics.

PMID- 17447378
TI  - The outcome of severe malnutrition in northwest Ethiopia: retrospective analysis
      of admissions.
AB  - OBJECTIVE: To assess the clinical profile and treatment outcome of children with
      severe malnutrition. PATIENTS AND METHODS: A retrospective study of 335 children
      with severe malnutrition was conducted in Gondar University hospital over a
      period of four years; September 1997 - August 2000. RESULTS: There were 175
      (52.2%) males and 160 (47.8%) females with severe malnutrition. Children below
      the age of 24 months constituted for 60.3% of all the admissions. Marasmus was
      the most common type of malnutrition, present in 174 (52.0%) of the patients.
      Kwashiorkor and marasmic kwashiorkor were seen in 78 (23.3%) and 83 (24.7%) of
      the patients respectively. The overall case fatality rate was 61 (18.4%) while 30
      (9.1%) abandoned treatment. Two hundred forty (72.5%) of the patients were
      discharged improved. The case fatality rates for the different types of
      malnutrition were 28.4% for marasmic kwashiorkor, 16.9% for kwashiorkor and 14.5%
      for marasmus. A statistically significant risk of death was observed in those
      with history of bottle feeding (OR 4.5, P-value < 0.01), diarrhea with severe
      dehydration (OR 3.05, P-value < 0.01), altered level of consciousness (OR 7.08, P
      value < 0.001), total serum protein of 5 g/dl and less (OR 3.45, P-value < 0.05)
      and patients having marasmic kwashiorkor (OR 2.55, P-value < 0.01). CONCLUSION:
      This study shows a high mortality rate of severe malnutrition despite
      hospitalization. The findings confirm the need for intensive management of severe
      malnutrition.

PMID- 17447379
TI  - The pattern of glaucoma in Menelik II Hospital Addis Ababa, Ethiopia.
AB  - OBJECTIVES: To describe the demographic and clinical profiles glaucoma and
      evaluate the magnitude of blindness among patients with glaucoma. PATIENTS AND
      METHODS: Cases with glaucoma that were seen at Menelik II hospital Addis Ababa
      between May 10, 1994 and May 9, 1997 were reviewed Data on relevant demographic
      and clinical variables were collected and analysed. RESULTS: A total of 1,586
      glaucoma patients were seen at the glaucoma clinic during the study period. The
      male to female ratio was 2:1. The mean age is 51.9 (SD 17.9) years. Those
      patients above the age of 40 years represented 78% of the total glaucoma
      population. The prevalence of glaucoma was highest (27.1%) in the age group of 51
      60 years. It was bilateral in 806 (51%) of the patients. Primary Open Angle
      Glaucoma (POAG) was the most frequent type documented in 631 (40%) of the
      patients, followed by Secondary Glaucomas in 605 (38%), Primary Angle Closure
      Glaucoma (PACG) in 285 (18%), Normal Tension Glaucoma (NTG) in 36 (2%), and
      Congenital Glaucoma in 33 (2%). Six hundred fifty six patients (41%) were blind
      either in one or both eyes. PACG was found to be potentially a blinding type of
      glaucoma, in which 53% of the patients suffered from blindness. In the other
      types, poor public awareness and lack of treatment services were the most
      important factors that largely precopitated the occurrence of blindness.
      CONCLUSION: We recommend that, in addition to improving the diagnostic and
      therapeutic facilities, intensive work be done to increase public awareness on
      the nature of the disease, to expand the infrastructure and to develop and
      rationally deploy the required human resources.

PMID- 17447380
TI  - Tubo-peritoneal infertility: comparision of pre-operative hysterosalpingography
      and laparotomy findings (Tikur Anbessa Hospital, 1995 - 2002).
AB  - OBJECTIVES: To assess the value of hysterosalpingography (HSG) in diagnosing
      abnormalities of the fallopian tube in infertile women suspected to have
      infertility associated with a tubo-peritoneal cause. PATIENTS AND METHODS:
      Laparotomy and hydrochromopertubation was performed on 294 women after HSG using
      oil soluble contrast medium. RESULTS: There were 241 women with HSG bilateral
      tubal block and 53 with patent tubes (19 bilateral and 34 unilateral). The
      operative findings were 214 bilateral obstructions and 80 tubal patencies (49
      bilateral and 31 unilateral). About 2/3 of the true patent tubes were identified
      by HSG. The true positive rate of HSG bilateral tubal occlusion was 89%. A
      quarter of HSG cornual occlusion was patent and 14% of the bilateral patent tubes
      were defective. The false negative rate among the bilateral patent tubes was 10%.
      The prediction of HSG tubal occlusion and patency was high. The false positive
      cornual block was significant and the association of its true positivity and
      tuberculous salpingitis was high. CONCLUSION: The HSG and laparotomy findings
      concurred in most of the cases. In the sub-Saharan Africa where three-fourth of
      female infertility is attributed to tubo-peritoneal cause, the diagnostic value
      of HSG is unquestionable as HSG is a simple outpatient investigation, is
      relatively affordable, has well establishied therapeutic advantages and is
      associated with low frequency of complications. In cornual occlusions, where
      genital tuberculosis is ruled out, and in patent tube, after some months of grace
      period, laparoscopy/laparotomy follow-up may be helpful.

PMID- 17447381
TI  - Prospective study of patients with hand injury: Tikur Anbessa University Teaching
      Hospital, Addis Ababa.
AB  - OBJECTIVES: To describe the nature of hand injuries among patients seen in a
      referral teaching hospital in Addis Ababa. PATIENTS AND METHODS: All six hundred
      and two patients with a total of 621 injured hands seen at the emergency out
      patient department of Tikur Anbessa University Hospital over a one- year period,
      May 1, 2003 - April 30, 2004 were evaluated and findings documented and analyzed.
      RESULTS: of the 602 patients, 511 (84.9%) were males and 91 (15.1%) females. The
      mean age was 28.3 years (males 28.8 years and females 25.4 years). The majority
      of the injuries 488 (81.1%) occurred either in a factory, on a street, at home or
      at a construction site. The commonest causes included machine accidents 195
      (32.4%), followed by crushing 95 (15.8%), road traffic accidents 83 (13.8%) and
      injury from a sharp object 80 (13.4%). Fifty six percent of all the patients
      (336/602) had been injured at work, of whom 156 of 195 (80.0%) had been working
      with an unguarded machine. Fifteen of those injured 195 (7.7%) had suffered a
      previous machine injury. Work related hand injuries occurred more often among
      manual workers 77.7% (261/336). Three hundred and seven of the 621 injured hands
      had one or more fractures (49.4%), 233 a severe soft tissue injury (37.5%), 126
      an amputation (20.3%), 40 a dislocation (6.4%), and 34 (5.5%) foreign bodies in
      the hands. Four hundred and sixty five (77.2%) arrived within eight hours of the
      injury, and this included the majority of those most severely injured.
      CONCLUSION: It is suggested that the provision of adequate safety guards on
      industrial machines, and their use, would significantly reduce the number of
      severe hand injuries occurring in Addis Ababa.

PMID- 17447382
TI  - The pattern of acute poisoning in a teaching hospital, north-west Ethiopia.
AB  - OBJECTIVES: Poisoning by means of hazardous chemicals through ignorance, mishap
      or intentionally is becoming a serious health problem worldwide. Epidemiological
      data on this important health issue are, however, scarce in Ethiopia. The purpose
      of this study is to assess the pattern of acute poisonings and determine the
      approaches employed for the management of poisoning. PATIENTS AND METHODS: The
      medical records of patients with acute poisonings presented to the Gondar
      University hospital between July 2001 and June 2004 were reviewed
      retrospectively. RESULTS: One hundred and two patients presenting to the
      emergency department of the hospital were due to acute poisoning; accounting for
      about 0.45% of emergency room admissions. Organophosphates, rat poison and
      alcohol were the commonly encountered poisoning agents (in about 70% of cases)
      mainly in adults possibly with suicidal or para-suicidal intention. The
      approaches employed in the management of poisoning mainly involved
      gastrointestinal decontamination procedures. Specific antidotes were used in a
      substantial number of patients. The fatality rate was 2.4%. CONCLUSION: Poisoning
      with suicidal intention is becoming a serious health problem particularly in
      adults. Pesticides are commonly used toxicants. The approaches in the management
      of poisoning are justifiable in some cases. However, much is to be done to
      improve the recording of patient-related information and record-keeping
      processes. Further large scale studies are required to investigate national
      trends of poisoning and factors associated with poisoning.

PMID- 17447383
TI  - Two cases of interathoracic pathologies presented as secondory hypertrophic
      osteoarthopathy.
AB  - The vast majority of cases of Hypertrophic osteoarthropathy are associated with
      intra thoracic neoplasms mainly broncogenic cancer and benign fibrous tumor. Less
      commonly extra thoracic pathologies can present with this disorder. Two cases are
      presented here. The first is a 50-years-old male who came with complaints of
      significant weight loss, chest symptoms and multiple upper extremities joint
      pain. The second case was a 44 years old female who presented similarly with
      chest symptoms, joint and bone pain limited to lower extremities bilaterally.
      Chest x-ray and x-ray of extremities were suggestive of secondary hypertrophic
      ostroarthropathy and intrathoracic masses. The first patient with bronchogenic
      carcinoma, bronchoscopy with biopsy conform the diagnosis. The second patient was
      operated and the operative biopsy result was consistent with benign pleural
      fibroma.

PMID- 17447384
TI  - Diastematomyelia: a case report with review of litratures.
AB  - Diastematomyelia is complete or partial sagital splitting of the spinal cord into
      two hemicords, each with its own central canal and pia surrounding it. We are
      reporting the clinical feature, radiological evidence and surgical outcome of a
      nine years old female child from Addis Ababa who was lately diagnosed to have
      Diastematomyelia. In addition, we have presented review of relevant literatures.

PMID- 17447385
TI  - Magnitude of episiotomy in a teaching hospital in Addis Ababa, Ethiopia.
AB  - OBJECTIVE: To assess the rate of Episiotomy in vaginal birth in Tikur Anbessa
      teaching Hospital and the associated factors that influences the use of
      episiotomy in the unit. METHODS: A cross-sectional study was conducted in the
      delivery unit of the Tikur Anbessa Hospital from May to September 2000. Data on
      mothers who delivered in the study period was collected using structured
      questionnaire. Variables on use of episiotomy, parity, fetal presentation,
      duration of labor, mode of delivery, Apgar scores at first and fifth minutes,
      indications for episiotomy and the practice of analgesia & anesthesia in the
      management of Episiotomy were collected Medical charts and the labor ward logbook
      were reviewed for collecting the data. RESULTS: A total of 917 deliveries were
      attended during the study period among which 672 mothers (83.1%) delivered
      vaginally. Among the vaginal deliveries, 270 (40.2%) mothers had episiotomy. Of
      these 203 (75.2%) mothers were primigravidae. Nulliparity (77.7% vs 21.3%), the
      duration of the second stage of labor more 90 minutes (76% vs. 13.8%) and
      instrumental delivery (86.2% vs. 13.8%) has been shown to be significantly
      associated to having episiotomy, while the birth weight and Apgar scores didn't
      show significant differences. Local anesthesia was used only in 71 (28.1%) cases
      among the 253 on whom information regarding the use of local anesthesia was
      retrieved. CONCLUSION: The rate of episiotomy is significantly higher than the
      recommended practice for many centers. Measures should be taken to lower the rate
      of episiotomy rate that include preparation of guidelines and protocols according
      to the standard and training and nurses, midwives and doctors on the selective
      use of episiotomy. The current practice of perineal repair without
      analgesia/anesthesia should be revised and making labor and delivery less painful
      needs to be advocated.

PMID- 17447386
TI  - Risk factors for anemia among pregnant women attending antenatal clinic at Jimma
      University Hospital, southwest Ethiopia.
AB  - OBJECTIVE: to determine anemia and its risk factors among pregnant women METHODS:
      A cross-sectional analytic study was carried out among pregnant women who came
      for antenatal care follow up for the first time to Jimma University hospital,
      Jimma town, southwestern Ethiopia from May-June 2005. RESULTS: A total of 168
      pregnant women who came for their first antenatal care visit to Jimma University
      hospital were enrolled in the study. A structured and interviewer administered
      questionnaire was used to collect data on the socio-demographic variables,
      dietary habit and other gynecologic and obstetric history. Dietary data were
      collected using food frequency questionnaire prepared for assessing nutritional
      factors for anemia. Sahli hemoglobinometer and a microscope were used for
      assessing hemoglobin level and stool for hookworm infection, respectively. Data
      were cleaned, edited and entered in to a computer and analyzed using SPSS for
      windows, version 11.0. Statistical tests were performed at the level of
      significance of 5%. The prevalence of anemia was 64/168 (38.2%) and the mean
      hemoglobin level was 11.3 mg/dl. Anemic cases were 4 times likely to have history
      of excess menstrual bleeding prior to the index pregnancy 2 times likely to have
      hook worm infection and 3 times likely not to have shoe wearing habit, 3 times
      likely to have birth intervals less than 24 moths between the previous pregnancy
      and index pregnancy (p < 0.05). CONCLUSION: This finding suggests the need for
      strengthening of interventions related to child spacing and raising awareness
      about family planning methods. All ANC attendants should be screened for anemia
      and hookworm infection at first visit and those anemic mothers and infected with
      hookworm should be treated appropriately. Health education should be given to
      pregnant mothers on family planning, and the need to gynecologic evaluation
      before pregnancy and the importance of wearing shoes to decrease hook worm
      infection and subsequent anemia.

PMID- 17447387
TI  - Emergency contraception: knowledge and practice of Gondar University students,
      northwest Ethiopia.
AB  - OBJECTIVES: To assess the knowledge and practice of Gondar University students
      regarding emergency contraceplion. PATIENTS AND METHODS: A university based cross
      sectional study was conducted in the University of Gondar in May 2004. All
      undergraduate students of the university were included in the study. A self
      administered anonymous questionnaire was used for data collection. RESULTS: A
      total of 2323 students (1764 males & 559 females) responded to the questionnaire.
      Five hundred fifty eight students (24.0%) thought that there are methods that can
      be used to prevent pregnancy when a woman had unprotected sex. Overall, 437
      students (18.8%) knew the correct methods of emergency contraception (pill or
      IUCD). Of those who mentioned pill as the only method of emergency contraception,
      285 (73.3%) said the pill should be used within 72 hours after unprotected sex.
      Only one student used pill as emergency contraceptive. Students in the health
      field have 6.8 times higher knowledge on emergency contraception compared to
      students of FBE. Generally, there was an increasing trend in the knowledge of
      students when their age and year of study increases. Married or divorced students
      had 3.36 times higher knowledge when compared with never married students.
      CONCLUSION: In general, except students in the health field, other students have
      low awareness about emergency contraception. Emergency contraceptive user rate is
      very low. Even in those who are aware of emergency contraception, the information
      they have regarding the methods that can be used and the timing of emergency
      contraception was not sufficient. Students should be provided with appropriate
      information regarding emergency contraception and access to emergency
      contraception should be improved in the university.

PMID- 17447388
TI  - Birth trauma among live born term neonates at a referral hospital in Addis Ababa,
      Ethiopia.
AB  - OBJECTIVE: To assess the occurrence, risk factors and outcomes of mechanical
      birth injuries among live term neonates. METHODS: A two-year retrospective case
      control study (September 2000-August 2002) was conducted in a referral hospital
      in Addis Ababa. RESULTS: One hundred and fifty cases and 358 controls were
      studied. Subgaleal hemorrhage was the commonest birth injury (61%). Primiparity,
      vacuum delivery, forceps delivery and birth weight > 3.5 kilograms were found to
      be strongly associated with birth trauma. Infants with subgaleal hemorrhage were
      more likely to be complicated than infants with other mechanical birth injuries.
      CONCLUSION: Indications and benefits of instrumntal delivery should be revised in
      our circumstances and prim gravid mothers should be evaluated carefully during
      ANC follow-up.

PMID- 17447389
TI  - Antiretroviral treatment adherence and its correlates in Addis Ababa, Ethiopia.
AB  - OBJECTIVE: To assess the degree of adherence with highly active antiretroviral
      therapy (HAART), and its correlates among adults with HIV/AIDS in Addis Ababa.
      PATIENTS AND METHODS: Cross-sectional survey of consecutive patients attending
      three ART centers in Addis Ababa complemented by semi-structured audiotaped in
      depth interviews with 10 purposively sampled patients on HAART Treatment
      adherence was defined as self-report of taking > or =95% of therapy correctly in
      a specified time period, depression measured using Beck's depression inventory,
      clinical data recorded by reviewing patients' charts, and knowledge about HAART
      assessed by questions in "Yes"/"No "format. RESULTS: 431 patients on HAART
      responded 81.2% of patients were > or =95% adherent by self report in the week
      before the assessment. The major reasons for non-adherence were: being too busy
      or simply forgot (33.9%) and being away from home (27.5%). Correlates of
      adherence included having regular follow-up, not being depressed having no side
      effects, a regimen that fitted the daily routine and satisfaction with the
      relationship with doctors. CONCLUSIONS: Self-reported adherence in our study was
      higher than that seen in developed countries. Recommendations to improve
      adherence include: provision of regular follow-up for patients, management of
      depression, forewarning of side effects of HAART, and creating medication
      schedules appropriate to patients' daily routines.

PMID- 17447390
TI  - Sero-prevalence of brucellosis in occupationally exposed people in Addis Ababa,
      Ethiopia.
AB  - OBJECTIVE: Brucellosis is a Zoonosis, recognized worldwide as a serious public
      health hazard and economically significant disease. The etiologic agent of this
      disease is a bacterial species of the genus Brucella that causes undulant fever,
      sterility and other systemic illnesses in human. Thus, the aim of this study was
      to undertake seroepidemiological study of brucellosis on occupationally exposed
      persons in Addis Ababa abattoirs enterprise and different dairy farms. METHODS:
      Three hundred thirty six human individuals were screened using Rose Bengal Plate
      Test (RBPT) and the sera were further subjected to 2- Mercapto Ethanol Test (2
      MET). Simultaneously, survey was conducted in farms and slaughterhouse to
      investigate epidemiological factors. RESULTS: An overall seroprevalence rate of
      4.8% (16/336) was determined by taking RBPT+/2MET+ as confirmatory test (P <
      0.05). Some of the risk factors contributing to the occurrence of the disease
      include occupation, gender, and unsafe handling of infected materials. Raw milk
      and meat consumption, lack of awareness and use of detergents were also found as
      important factors. CONCLUSION: The seroprevalence of brucellosis is expected to
      be more in other areas of the Region, where there is high human-animal contact
      and high number of cattle population with a respective traditional system of
      animal rearing.

PMID- 17447391
TI  - A placebo controlled double blind clinical trial of mitomycin C in primary
      trabeculectomy in Ethiopian patients.
AB  - OBJECTIVE: To determine if surgery with mitomycin has an increased success rate
      in reducing introccular pressure after trabeculectomy in Ethiopian patients
      METHODS: A double blind clinical trial using mitomycin C and placebo during
      primary trabeculectomy was carried out on 31 patients and 31 controls. 31
      patients and 28 controls completed the study period Post operative intra ocular
      pressure and post operative complications were assessed RESULTS: There was no
      statistically significant difference in the postoperative intra ocular pressure
      in both groups (p = 0.6 95% CI). However there was a statistically significant
      higher rate of complications in the cases when compared to the controls (p = .002
      95% CI). CONCLUSION: A controlled study with adequate power using different
      dosages of mitomycin is recommend

PMID- 17447392
TI  - Prevalence of anti-toxoplasma Gondii antibodies in Turkish blood donors.
AB  - OBJECTIVE: Toxoplasmosis is caused by an obligate intracellular protozoan
      parasite, Toxoplasma gondii. Most of these infections are asymptomatic or benign,
      but may cause severe or fatal consequences in immunodeficient patients,
      transplant recipients, and in the fetus. Transmission may occur by eating
      uncooked meat, contaminated vegetables, blood transfusion, organ transplantation,
      and across the placenta from the mother to the fetus. IgG antibodies to T. gondii
      may persist in the serum at high titers for years. In the present study, our aim
      was to determine prevalence of anti- T. gondii IgG and IgM antibodies in Turkish
      blood donors. METHODS: A total samples from 385 healthy blood donors from
      Kayseri, Turkey were examined for anti- T. gondii antibodies by indirect
      fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA).
      RESULTS: The seroprevalence of the anti- T. gondii IgG and IgM antibodies was
      19.5%, 2.33% respectively by IFAT and 20.25%, 2.33% by ELISA. CONCLUSION: It is
      suggested that all blood donors should be screened for toxoplasmosis before
      transfusion

PMID- 17447393
TI  - Meningiomas: clinical correlates, skull x-ray, CT and pathological evaluations.
AB  - OBJECTIVE: To assess the frequency and the diagnostic performance of plain skull
      x-ray and and CT of meningiomas. METHODS: All pathologically diagnosed
      intracranial meningiomas in patients seen at Tikur Anbessa Hospitals were
      reviewed. RESULTS: Between December 1999 and July 2004 there were 25
      histologically diagnosed cases of meningioma at the Tikur Anbessa Hospital (TAH).
      The duration of symptoms was ranging from 0.5-10 yrs. (mean 2.4 +/- 2.1 yrs) and
      age ranging from 21-57 yrs (mean age of 49.3 +/- 10 yrs.) with M:F ratio of
      1.2:1. Blurring of vision was the commonest clinical presentation. Clinical
      correlates, skull x-rays, computerized tomographic results and pathology are
      evaluated. Plain skull x-ray findings were normal in 12/23 (52%); 10/23(43%) of
      the cases had non-specific sellar changes of raised intra-cranial pressure.
      Twenty-three of the 25 meningiomas had CT scanning done, and CT diagnosed 17/23
      (74%) meningiomas correctly. Two meningiomas were unusual in location: one was
      intranasal and the other was intra-ventricular. Parasellar tumors were frequent
      sites of misdiagnosis. The commonest locations were parasellar and cerebral
      convexity, each accounting for 6/25 (24%) of the cases. The commonest CT
      observation was intense and homogeneous enhancement 15/23 (65%). Meningothelial
      meningioma was the commonest cellular type accounting for 11/25 (46%) of the
      pathologies followed by the transitional 4/25 (16%) and the atypical and
      psammomatous types, each with equalfrequency, 3/25 (12%). CONCLUSION: CT scan had
      a diagnostic accuracy of 83%, sensitivity of 74%, specificity of 95%, positive
      predictive value (PPV) of 95%, and negative predictive value (NPV) of 75%.
      Statistical analysis verifies the pre-operative reliability for diagnosing
      meningiomas by CT scanning.

PMID- 17447394
TI  - Antibacterial and antifungal activities of extracts of combretum molle.
AB  - OBJECTIVE: In traditional medical practices of Ethiopia the aqueous extracts
      obtained from the stem bark of Combretum molle (R. Br. Ex. G. Don.) Engl & Diels
      (Combretaceae) have a longstanding reputation for the treatment of liver diseases
      malaria and tuberculosis. Owing to the widespread traditional uses of this plant,
      the studyinvestigated the antimicrobial activity the bark extract of this plant
      against Gram positive and and Gram negative bacteria. METHODS: Petroleum ether,
      dichloromethane and acetone fractions of the bark of the plant were prepared by
      soxhlet extraction and screened for their antimicrobial activity. The acetone
      fraction exhibited a powerful activity and was therefore further tested against
      twenty-one bacterial and six fungal strains. The minimum inhibitory concentration
      (MIC) of this extract was determined by checker board technique using nutrient
      agar medium. The zones of inhibition produced by the extract against bacteria and
      fungi were determined and compared by disc diffusion technique with those of pure
      ciprofloxacin and griseofulvin, respectively. RESULTS: The highest antibacterial
      action of the acetone extract was against the Gram negative organisms EscherIchia
      coli and Shigella spp with an MIC value of 50 mg/ml. The activity of the extract
      against these bacteria was comparable to that of ciprofloxacin when assessed by
      the disc diffusion technique. Among the fungal strains tested Candida albicans
      showed high susceptibility to the extract and growth was completely inhibited at
      a concentration of 400 microg/ml. At the same concentration, the acetone extract
      and the standard antifungal drug griseofulvin produced comparable zones of
      inhibition on C. albicans. Studies on the mode of action of the extract indicated
      that it was bactericidal and fungicidal. The antimicrobial activity of the
      extract was attributed to the high amount of hydrolysable tannins present in the
      bark of the plant. CONCLUSION: The acetone extract of the stem bark of C. molle
      has the potential for use as a natural antimicrobial agent. Further in vivo
      antimicrobial, phytochemical and toxicological studies are requireed to evaluate
      the chemotherapeutic effect of the plant.

PMID- 17447395
TI  - Anti-malarial activity of withania somnifera L. Dunal extracts in mice.
AB  - OBJECTIVE: This study aims at investigating the in vivo antiplasmodial activity
      of a traditionally used medicinal plant, Withania somnifera, L. Dunal,
      (Solanaceae). METHODS: Rodent malaria parasite, Plasmodium berghei, 0.2 ml of x
      l0(7) parasites, was inoculated into Swiss albino mice intraperitoneally.
      Extracts were administered by intra gastric tube daily for four days starting
      from the day of parasite inoculation. Negative controls received the same amount
      of solvent used to suspend the exracts and the positive controls were given
      chloroquine by the same route. Parasite suppressive effect and effects on body
      weight, packed cell volume (PCV) and body temperature were determined. RESULTS:
      Parasitemia percent inhibition of W. somnifera roots and root barks were 50.43%
      and 29.13% respectively, with 600 mg/kg dose. Inhibition was statistically
      significant at all dose levels, compared to the negative controls (p < 0.05), and
      maximum inhibition was seen at 600 mg/kg. CONCLUSION: Extracts of the leaves and
      root barks of W. somnifera showed parasite suppressive effect and a protective
      effect on PCV drop (at higher doses), both in dose-related fashions. However, the
      effects on body weight and body temperature falls are inconclusive.

PMID- 17447396
TI  - Intramedullary cavernous haemangioma of spinal cord: a case report and literature
      review.
AB  - A 27-year-old female patient with progressive paraparesis and incontinence of
      urine of 9 months duration was managed at Tikur Anbessa Hospital, Neurosurgery
      unit, Department Of Surgery, Medical Faculty, Addis Ababa University, Addis
      Ababa. Thoracic myelography showed an intramedullary mass at T3-T5 levels of the
      spinal cord. Histopathology revealed cavernous haemangioma. Near total surgical
      removal of the haemangioma was done. and the patient put on intensive
      physiotherap. Cavernous haemangioma should be suspected in the differential
      diagnosis of patients with progressive deterioration of spinal cord function.
      Total surgical excision of the lesion is the current treatment modality.

PMID- 17447397
TI  - Viable pregnancies in women with different mullerian duct anomalies.
AB  - Some of the fascinating developmental anomalies encountered by Obstetricians and
      Gynecologists are mullerian duct disorder of various types. The diagnosis is
      usually made during workup for infertility, recurrent pregnancy loss or cyclic
      pelvic pain. Because of embryologic developmental structural share and proximity,
      it is not uncommon to find mullerian duct, urinary tract and skeletal anomalies
      concurrently. Three parous women with different mullerian duct malformations
      preoperatively diagnosed as ovarian tumor, ectopic pregnancy and footling breech
      are reported Intraoperatively, the first case was found to have uterine didelphys
      with blind hemivagina, lumbosacral bones defect and hypoplastic pelvic kidney. In
      the second case, bicornuate uterus with viable pregnancy and in the third case,
      fetus and placenta in separate cavity of partially septated uterus were
      identified Literature on the embryologic association of mesonephric and
      paramesonephric ducts anomaly, the reproductive outcome and place of metroplasic
      surgery are reviewed.

PMID- 17447398
TI  - Juvenile polyposis in an Ethiopian family.
AB  - An 8-year-old boy from Arsi, central Ethiopia, seen at Tikur Anbessa Hospital, a
      tertiary and teaching hospital, Addis Ababa, Ethiopia, with a history of
      protruding mass per anum during straining at defecation and micturition and
      rectal bleeding of 12 months, diagnosed to have juvenile polyposis is presented
      The condition was complicated by severe anemia and hypoproteinemia. Following
      abdominal surgery (subtotal colectomy, ileoproctostomy and proctoscopic diathermy
      of rectal polyps) and supportive measures, the bleeding stopped and his general
      condition improved His father and two of his three siblings were also proved to
      have colonic polyposis, earlier. Clinical presentation, investigations, intra
      operative and histologic findings, and prognosis are discussed with background
      literature review.

PMID- 17447399
TI  - The 18-second doctor.

PMID- 17447400
TI  - How they do it better. Protection from the sun.

PMID- 17447401
TI  - How they do it better. Skimpy portions and satisfied stomachs.

PMID- 17447402
TI  - How they do it better. Novel aides for the aged.

PMID- 17447403
TI  - How they do it better. Straight facts about the birds and bees.

PMID- 17447404
TI  - How they do it better. The afternoon nap attack.

PMID- 17447405
TI  - How they do it better. Abuse as a disease, not a crime.

PMID- 17447406
TI  - How they do it better. Getting paid for parenting.

PMID- 17447407
TI  - How they do it better. Free health coverage for all.

PMID- 17447408
TI  - How they do it better. More stressed, but still safer.

PMID- 17447409
TI  - My love with monoamine oxidase, iron and Parkinson's disease.

PMID- 17447410
TI  - Levodopa in the treatment of Parkinson's disease.
AB  - Levodopa is the most efficacious drug to treat the symptoms of Parkinson's
      disease (PD) and is widely considered the "gold standard" by which to compare
      other therapies, including surgical therapy. Response to levodopa is one of the
      criteria for the clinical diagnosis of PD. A major limiting factor in levodopa
      therapy is the development of motor complications, namely dyskinesias and motor
      fluctuations. The ELLDOPA study was designed to determine if levodopa affected
      the progression of PD. This double-blind randomized study showed that the
      subjects treated with levodopa for 40 weeks had less severe parkinsonism than the
      placebo treated subjects even after a 2-week washout of medications, with the
      highest dose group showing the greatest benefit. Thus, levodopa may actually have
      neuroprotective value, but the result was not conclusive of slowing disease
      progression, because the same result could have arisen from a very long-lasting
      symptomatic benefit of levodopa.

PMID- 17447411
TI  - Changing dopamine agonist treatment in Parkinson's disease: experiences with
      switching to pramipexole.
AB  - 1202 patients suffering from Parkinson's disease switched from other dopamine
      agonists to pramipexole under open conditions either abruptly or in an
      overlapping, gradual manner. Mostly insufficient effectiveness motivated the
      switch. The investigators gave equal preference to either an abrupt or an
      overlapping switch to pramipexole in this observational study. There was a
      tendency in favour of the overlapping switch procedure in those patients who were
      on a relatively higher dose of a dopamine agonist before the switch. The switch
      was performed because the investigators expected the effect of pramipexole on
      tremor, motor functions and depression/anhedonia to be better compared with
      previous dopamine agonists. The main reasons for switching to pramipexole (anti
      tremor effect, anti-depressive/anti-anhedonic effect) as given by the physicians
      at baseline came up to expectations. The switch to pramipexole mostly yielded
      further improvements irrespective of the mode of switching.

PMID- 17447412
TI  - The DONPAD-study--treatment of dementia in patients with Parkinson's disease with
      donepezil.
AB  - Inhibition of acetylcholinesterase improves symptoms of dementia in patients with
      Parkinson's disease (PD). Dementia in PD has a cumulative incidence of up to 80%
      and is mainly caused by a distinct cholinergic deficit. Objectives of this
      investigator initiated multicenter open label trial were to confirm the efficacy
      of donepezil in the treatment of dementia in PD patients and to investigate the
      tolerability and safety of donepezil. The Mini Mental State Examination (MMSE)
      score significantly increased in patients, who finished the trial. A detailed
      analysis of the various items of the MMSE revealed, that only task performance of
      orientation and recall significantly improved. Scores of the short syndrome test
      and the Clinical Global Impression Scale improved, motor impairment did not
      increase. Only 14 out of 24 PD patients finished the trial due to predominant
      onset of vomiting, nausea, dizziness and confusion. This may result from the
      titration regime of donepezil, that allows only 5 and 10 mg dosages. Participants
      with premature study termination had a significant longer duration of PD, less
      motivation and sleep disturbances at night. Treatment with donepezil was only
      effective in PD patients with dementia, who experience nearly no side effects
      from the drug.

PMID- 17447413
TI  - PD-related psychosis: pathophysiology with therapeutical strategies.
AB  - Parkinson's disease (PD) is a chronic, neurodegenerative disease with
      degeneration of the central dopaminergic neurons in the substantia nigra, leading
      to a depletion of dopamine (DA) in the striatum. This depletion causes the
      clinical hallmarks of this disease: bradykinesia, hypokinesia, rigidity, tremor
      and postural instability. Besides these well known motor symptoms, non-motor
      symptoms may develop, such as hyposmia, sleep disorders, autonomic disturbances,
      depression, cognitive impairment and psychosis. Pathophysiological mechanisms
      underlying these symptoms not only comprise Lewy body pathology in the central
      dopaminergic system, but also in the noradrenergic, serotinergic and cholinergic
      transmittersystems. Indeed, in Parkinson's disease, about 30-40% of the patients
      suffers fluctuating psychotic symptoms, mainly paranoid delusions and/or visual
      or acoustic hallucinations, symptoms considered to represent major contributors
      to patient and caregiver distress and nursing home placement. Endogenous (related
      to the disease process itself) as well as exogenous (related to therapeutical
      interventions) psychotogenic factors may contribute to the development of
      psychotic symptoms in PD. Therapeutical strategies, therefore, are aimed to
      reduce both endogenous and exogenous factors. To reduce endogenous psychotogenic
      factors, cholinesterase inhibitors, suggested to reduce cognitive deterioration,
      now seem to be the drugs of choice. In exogenously induced psychotic symptoms,
      atypical antipsychotics are considered the most effective. However, as psychotic
      symptoms in PD are often influenced by both endogenous and exogenous factors, a
      combination of both strategies may be preferred.

PMID- 17447414
TI  - Antioxidant capacity in postmortem brain tissues of Parkinson's and Alzheimer's
      diseases.
AB  - Oxidative stress has been associated with damage and progressive cell death that
      occurs in neurodegenerative disorders such as Parkinson's disease (PD) and
      Alzheimer's disease (AD). The aim of this study was to investigate the
      antioxidant capacity in postmortem motor cortex (MC), nucleus caudatus (NC),
      gyrus temporalis (GT) and substantia nigra (SN) from controls (C) and patients
      with PD and AD. The initial samples consisted of 68 subjects of PD, AD and C.
      Brains were matched for age, sex and postmortem time. Brain tissue was
      homogenized in a phosphate buffer pH 7.3 and separated with two-step
      centrifugation at 15,000rpm for 30 min and 15,000 rpm for 10 min at 4 degrees C.
      Antioxidant capacity in the supernatants was measured using the oxygen radical
      absorbance assay (ORAC). The results showed that in the SN of parkinsonian's
      brain the balance between production of free radicals and the neutralization by a
      complex antioxidant system is disturbed. No changes in the antioxidant capacity
      of postmortem MC and NC of parkinsonian's brain in comparison with C were found.
      In the SN of parkinsonian's brain, antioxidant capacity seems to be lower in
      comparison with C (p < 0.05). Antioxidant capacity against peroxyl radical showed
      that MC of AD patients was lower than in the MC of C (p < 0.005). In NC of AD
      patients the antioxidant capacity against hydroxyl radical was increased in
      comparison with C (p < 0.04). No changes in the antioxidant capacity were found
      in brain tissues of AD in comparison with C, when CuSO4 was used as a free
      radical generator.

PMID- 17447415
TI  - Apoptosis inhibition in T cells triggers the expression of proinflammatory
      cytokines--implications for the CNS.
AB  - Stimulation of death receptors such as CD95 or TNF-R1 results in rapid onset of
      apoptosis. Here we show that inhibition of death receptor-induced apoptosis by
      the broad range caspase inhibitor ZVAD causes a switch from apoptotic to
      proinflammatory signaling. In previous studies we have reported that caspase
      inhibitors induce expression of various proinflammatory cytokines in CD95
      stimulated primary T cells, such as TNF-alpha, IFN-gamma and GM-CSF. In this
      study we provide further evidence for the proinflammatory activity of CD95.
      Stimulation of CD95 by agonistic antibodies (7C11) resulted in expression of IL-2
      in primary T cells, which was further enhanced when caspase activity was blocked
      by ZVAD. Moreover, CD95 triggered expression of IL-4 and IL-8 when caspase
      activity was inhibited, but not in the absence of ZVAD. Our findings are of
      significant importance for the CNS as changes in the cytokine pattern in the
      periphery affects the entry of various immune cells into the brain. Moreover,
      invading activated T cells can also directly influence the cytokine profile
      within the brain, triggering signaling cascades that eventually lead to neuronal
      cell death. The use of caspase inhibitors to prevent apoptotic cell death should
      be carefully evaluated in the management of systemic and CNS diseases.

PMID- 17447416
TI  - Molecular mechanism of the relation of monoamine oxidase B and its inhibitors to
      Parkinson's disease: possible implications of glial cells.
AB  - Monoamine oxidases A and B (MAO A and MAO B) are the major enzymes that catalyze
      the oxidative deamination of monoamine neurotaransmitters such as dopamine (DA),
      noradrenaline, and serotonin in the central and peripheral nervous systems. MAO B
      is mainly localized in glial cells. MAO B also oxidizes the xenobiotic 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP) to a parkinsonism-producing neurotoxin,
      1-methyl-4-phenyl-pyridinium (MPP+). MAO B may be closely related to the
      pathogenesis of Parkinson's disease (PD), in which neuromelanin-containing DA
      neurons in the substantia nigra projecting to the striatum in the brain
      selectively degenerate. MAO B degrades the neurotransmitter DA that is deficient
      in the nigro-striatal region in PD, and forms H2O2 and toxic aldehyde metabolites
      of DA. H2O2 produces highly toxic reactive oxygen species (ROS) by Fenton
      reaction that is catalyzed by iron and neuromelanin. MAO B inhibitors such as L-(
      )-deprenyl (selegiline) and rasagiline are effective for the treatment of PD.
      Concerning the mechanism of the clinical efficacy of MAO B inhibitors in PD, the
      inhibition of DA degradation (a symptomatic effect) and also the prevention of
      the formation of neurotoxic DA metabolites, i.e., ROS and dopamine derived
      aldehydes have been speculated. As another mechanism of clinical efficacy, MAO B
      inhibitors such as selegiline are speculated to have neuroprotective effects to
      prevent progress of PD. The possible mechanism of neuroprotection of MAO B
      inhibitors may be related not only to MAO B inhibition but also to induction and
      activation of multiple factors for anti-oxidative stress and anti-apoptosis:
      i.e., catalase, superoxide dismutase 1 and 2, thioredoxin, Bcl-2, the cellular
      poly(ADP-ribosyl)ation, and binding to glyceraldehydes-3-phosphate dehydrogenase
      (GAPDH). Furthermore, it should be noted that selegiline increases production of
      neurotrophins such as nerve growth factor (NGF), brain-derived neurotrophic
      factor (BDNF), and glial cell line-derived neurotrphic factor (GDNF), possibly
      from glial cells, to protect neurons from inflammatory process.

PMID- 17447418
TI  - The relationship of early studies of monoamine oxidase to present concepts.
AB  - The development of our understanding of monoamine oxidase (MAO), of its role in
      the metabolism of amines and of the therapeutic usefulness of MAO inhibitors
      (MAOIs) have evolved, slowly at times and rapidly at other times, with leaps
      propelled by new discoveries, new techniques and new insights. Moussa Youdim was
      one of the major contributors to propulsion of several of these leaps, including
      the detection of multiple forms of MAO, the descriptions of their properties,
      active sites and substrates, the use of MAOIs for enhancement of DOPA in treating
      Parkinson's disease and the evolution of MAO-B inhibitors from mere enzyme
      inhibitors to lead compounds in the discovery of neuroprotective agents for use
      in degenerative neurological diseases. Since others will be describing the more
      recent developments in this field, I thought it would be of interest and
      instructive to recount the unfolding of our early understanding of MAO, dating
      from its discovery until the events that first suggested that drugs that inhibit
      MAO might be neuroprotective. While even the earliest observations about MAO were
      valid, they were often misinterpreted or confusing, whereas others were
      predictive of several of our newer concepts of MAO and of side effects
      encountered in patients treated with MAOIs.

PMID- 17447417
TI  - Involvement of type A monoamine oxidase in neurodegeneration: regulation of
      mitochondrial signaling leading to cell death or neuroprotection.
AB  - In neurodegenerative diseases, including Parkinson's and Alzheimer's diseases,
      apoptosis is a common type of cell death, and mitochondria emerge as the major
      organelle to initiate death cascade. Monoamine oxidase (MAO) in the mitochondrial
      outer membrane produces hydrogen peroxide by oxidation of monoamine substrates,
      and induces oxidative stress resulting in neuronal degeneration. On the other
      hand, a series of inhibitors of type B MAO (MAO-B) protect neurons from cell
      death. These results suggest that MAO may be involved in the cell death process
      initiated in mitochondria. However, the direct involvement of MAO in the
      apoptotic signaling has been scarcely reported. In this paper, we present our
      recent results on the role of MAO in activating and regulating cell death
      processing in mitochondria. Type A MAO (MAO-A) was found to bind an endogenous
      dopaminergic neurotoxin, N-methyl(R)salsolinol, and induce apoptosis in
      dopaminergic SH-SY5Y cells containing only MAO-A. To examine the intervention of
      MAO-B in apoptotic process, human MAO-B cDNA was transfected to SH-SY5Y cells,
      but the sensitivity to N-methyl(R)salsolinol was not affected, even though the
      activity and protein of MAO-B were expressed markedly. MAO-B oxidized dopamine
      with production of hydrogen peroxide, whereas in control cells expressing only
      MAO-A, dopamine autoxidation produced superoxide and dopamine-quinone, and
      induced mitochondrial permeability transition and apoptosis. Rasagiline and other
      MAO-B inhibitors prevent the activation of apoptotic cascade and induce
      prosurvival genes, such as bcl-2 and glial cell line-derived neurotrophic factor,
      in MAO-A-containing cells. These results demonstrate a novel function of MAO-A in
      the induction and regulation of apoptosis. Future studies will clarify more
      detailed mechanism behind regulation of mitochondrial death signaling by MAO-A,
      and bring out new strategies to cure or ameliorate the decline of neurons in
      neurodegenerative disorders.

PMID- 17447419
TI  - Isatin, an endogenous MAO inhibitor, and a rat model of Parkinson's disease
      induced by the Japanese encephalitis virus.
AB  - A single dose of isatin (indole-2,3-dione)(i.p.), an endogenous MAO inhibitor,
      significantly increased norepinephrine and 5-hydroxytryptamine concentrations in
      the rat brain and also significantly increased acetylcholine and dopamine (DA)
      levels in the rat striatum. Urinary isatin concentrations in patients with
      Parkinson's disease tend to increase according to the severity of disease. We
      have developed a rat model of Parkinson's disease induced by the Japanese
      encephalitis virus (JEV). The distribution of the pathological lesions of JEV
      rats resemble those found in Parkinson's disease. Significant behavioral
      improvement was observed in JEV-rats after isatin, L-DOPA and selegiline
      administration using a pole test. Both isatin and selegiline prevented the
      decrease in striatum DA levels of JEV-rats. The increased turnover of DA
      (DOPAC/DA) induced by JEV was significantly inhibited by isatin, but not
      selegiline. These findings suggest that JEV-infected rats may serve as a model of
      Parkinson's disease and that exogenously administered isatin and selegiline can
      improve JEV-induced parkinsonism by increasing DA concentrations in the striatum.

PMID- 17447420
TI  - Isatin interaction with glyceraldehyde-3-phosphate dehydrogenase, a putative
      target of neuroprotective drugs: partial agonism with deprenyl.
AB  - There is evidence that the binding of deprenyl, a monoamine oxidase (MAO) B
      inhibitor, and other propargylamines to glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) is primarily responsible for their neuroprotective and antiapoptotic
      effects. Thus, GAPDH may be a target for other neuroprotective drugs. Using two
      independent approaches, radioligand analysis and an optical biosensor technique,
      we demonstrate here that GAPDH also interacts with the endogenous, reversible MAO
      B inhibitor, isatin. Deprenyl inhibited both [3H]isatin binding to GAPDH, and the
      binding of this enzyme to an isatin analogue, 5-aminoisatin, immobilized on to an
      optical biosensor cell. Another MAO inhibitor, tranylcypromine, was ineffective.
      Both deprenyl and isatin inhibited GAPDH-mediated cleavage of E. coli tRNA, and
      their effects were not additive. We suggest that isatin may be an endogenous
      partial functional agonist of deprenyl in its effect on GAPDH and GAPDH-mediated
      RNA cleavage. Changes in level of endogenous isatin may influence the
      neuroprotective effect of deprenyl in vivo.

PMID- 17447421
TI  - Inhibition of amine oxidases by the histamine-1 receptor antagonist hydroxyzine.
AB  - The effects of the drug hydroxyzine on the activities of the rat liver monoamine
      oxidases (EC 1.4.3.6; MAO) and the membrane-bound and soluble forms of bovine
      semicarbazide-sensitive amine oxidase (EC 1.4.3.6; SSAO) were studied.
      Hydroxyzine was found to be a competitive inhibitor of MAO-B (Ki - 38 microM),
      whereas it had a low potency towards MAO-A (IC50 > 630 microM). Although it was a
      relatively potent competitive inhibitor of bovine plasma SSAO (Ki approximately
      1.5 microM), it was a weak inhibitor of the membrane-bound form of the enzyme
      from bovine lung (IC50 approximately 1 mM). These findings extend our knowledge
      of the drug binding capabilities of the amine oxidases and suggest that these
      interactions may contribute to the complex actions of this drug.

PMID- 17447422
TI  - Neuroprotection for Parkinson's disease.
AB  - Although still a disorder of unknown etiology, Parkinson's disease (PD) has
      provided a number of clues that have led to clinical trials of neuroprotection.
      For example, defects in mitochondrial metabolism and evidence for oxidative
      stress in PD have fostered therapeutic interventions aimed at slowing disease
      progression. More than a dozen compounds already have been tested in PD for
      disease modification, and others are in planning stages for clinical trials. The
      challenge is to find a highly effective therapy halting disease progression
      (beyond the relatively modest clinical effect exemplified by recent findings with
      coenzyme Q-10 treatment administered at 1200mg/day). Clinical exam-based ratings
      and disability assessments still serve at providing the primary evidence of
      efficacy. However, with surrogate biomarkers such as radiotracer neuroimaging of
      the dopaminergic system, the pace of clinical investigation can be increased.
      Recent years have seen the utilization of more sensitive study methods in PD
      neuroprotection research, such as staggered wash-in, 2 x 2 factorial, and
      "futility" trial designs. The results of several ongoing PD neuroprotection
      trials are planned for release in the near future.

PMID- 17447423
TI  - Marker for a preclinical diagnosis of Parkinson's disease as a basis for
      neuroprotection.
AB  - Neuroprotective therapy is a pivotal aim in the treatment of the relentlessly
      progressive disorder Parkinson's disease. However, more than 60% of the
      dopaminergic neurons of the substantia nigra have already degenerated, when the
      diagnosis may be established. At this "advanced stage" neuroprotective strategies
      will - if at all - only have limited effect. It is, therefore, essential to
      establish markers to identify subjects at risk before motor manifestation. A
      number of such "premotor" signs have been discovered and investigated lately.
      Such signs include a genetic vulnerability and hyperechogenicity of the
      substantia nigra as well as premotor symptoms like olfactory and autonomic
      dysfunction, depression, REM sleep behaviour disorder, visual and
      neuropsychological impairment. Moreover, first signs of affection of the
      substantia nigra like PET and SPECT abnormalities and slight motor signs can be
      included, as they may be detected before a definite diagnosis can be made.
      Although most of these signs and symptoms are unspecific if singularly evaluated
      a combination of these features may indeed be valuable to detect a subgroup of
      the population at risk for PD. However, future studies are necessary to establish
      the predictive value of these "markers" singularly and in combination.

PMID- 17447424
TI  - Assessing neuroprotection in Parkinson's disease: from the animal models to
      molecular neuroimaging in vivo.
AB  - An important goal in Parkinson's Disease research is to identify neuroprotective
      therapy, and the interaction between basic science and clinical research is
      needed to discover drugs that can slow or halt the disorder progression. At
      present there is not a perfect animal model of PD to test neuroprotective
      strategies, however the models that portray the basic characteristics needed are
      toxin-induced and gene-based models. The first group comprehends 6-OHDA e MPTP
      and recently rotenone, paraquat and epoxomicin treated animals that shows some of
      human disease characteristics. Gene-based models are various and, even if with
      limits, they seem suitable models to test neuroprotection in PD since they
      present replicable lesions, a predictable pattern of neurodegeneration and a well
      characterized behavior, biochemistry and morphology to assist in the
      understanding of induced changes. In clinical trials researchers have first used
      as marker of disease progression clinical scores and motor tasks which are
      limited by the potential symptomatic effect of tested drugs and are not useful in
      the pre-clinical phases of PD. Recently has emerged the important role of
      neuroimaging (Dopamine Transporter SPECT, 18FDopa-PET) as surrogate biomarker of
      PD progression. Even if there are still concerns about the influence of
      regulatory effects of tested drugs, neuroimaging features could represent a good
      outcome measure to evaluate PD progression and putative neuroprotective effect of
      pharmacological and non-pharmacological manipulations.

PMID- 17447425
TI  - Deprenyl: from chemical synthesis to neuroprotection.
AB  - During the last decades (-)-deprenyl has become the golden standard of MAO-B
      inhibitors. It possesses dopamine potentiating and antioxidant properties;
      however, its effects cannot be explained solely by the enzyme inhibitory action.
      (-)-Deprenyl prevents the toxicity of certain selective neurotoxins and recently
      it was demonstrated to increase cell-cell adhesion as well. The complexity of its
      pharmacological effects reflects the action of both the parent compound and the
      active metabolites. (-)-Deprenyl and related propargylamines (DRPs) show
      neuroprotective features in a variety of in vitro and in vivo models that is
      dependent on the propargyl moiety. The main presumptive targets to date include
      glyceraldehyde-3-phosphate dehydrogenase, poly(ADP-ribose) polymerase, some
      kinase cascades, as well as pro- and antiapoptotic proteins, beside the
      inhibition of MAO-B. The antiapoptotic activity of DRPs converges upon the
      maintenance of mitochondrial integrity, due to the initiation of a complex
      transcriptional program, the details of which are yet to be elucidated.

PMID- 17447426
TI  - The use of rasagiline in Parkinson's disease.
AB  - Rasagiline is a novel, potent, irreversible inhibitor of monoamine oxidative B
      developed for the symptomatic treatment of Parkinson's disease. The drug has
      shown efficacy in improving motor features in both early and advanced Parkinson's
      disease patients. The drug appears to be well tolerated and its once daily fixed
      dose formulation should make for excellent compliance. Rasagiline has also
      demonstrated important neuroprotective properties in both in vitro and in vivo
      laboratory studies. A provisional study of neuroprotection in a delayed start
      clinical trial of early PD patients has also suggested that this benefit may be
      translated to the clinic. Additional clinical trials are underway to confirm
      this.

PMID- 17447427
TI  - Novel neuroprotective neurotrophic NAP analogs targeting metal toxicity and
      oxidative stress: potential candidates for the control of neurodegenerative
      diseases.
AB  - A large body of data indicates that a cascade of events contributes to the
      neurodegeneration in Alzheimer's disease (AD) and Parkinson's disease (PD). Metal
      (Fe, Cu, Zn) dyshomeostasis and oxidative stress are believed to play a pivotal
      role in the pathogenesis of these diseases. Accordingly, multifunctional
      compounds combining metal chelating and antioxidative activity hold a great
      promise as potential drugs for treating AD and PD. In this study, two novel
      NAPVSIPQ (NAP) analogs (M98 and M99) with potential antioxidant-metal chelating
      ability were designed and investigated, aiming to improve the poor metal
      chelating and antioxidative activity of NAP. Our studies showed that both M98 and
      M99 formed stable metal (Fe, Cu, Zn) complexes in water and demonstrated good
      metal (Fe, Cu, Zn) chelating properties as opposed to the poor metal (Fe, Cu, Zn)
      chelating properties of their parent peptide NAP. M98 and M99 exhibited
      significant inhibition of iron-induced lipid peroxidation in rat brain
      homogenates at concentrations of > or = 30 microM, while NAP failed to show any
      inhibition even at 100 microM. In human neuroblastoma cell (SH-SY5Y) culture, M98
      and M99 at 1 microM completely protected against 6-hydroxydopamine (6OHDA)
      toxicity with potency similar to NAP and desferal (DFO), a strong iron chelator
      and a highly potent radical scavenger. In PC12 cell culture, M98 at the range of
      0.001-1 microM displayed potent protection against 6-OHDA toxicity, comparable to
      NAP and DFO. These results suggest that M98 and M99 deserve further investigation
      as potential drug candidates for neuroprotection.

PMID- 17447428
TI  - Acute and chronic effects of developmental iron deficiency on mRNA expression
      patterns in the brain.
AB  - Because of the multiple biochemical pathways that require iron, iron deficiency
      can impact brain metabolism in many ways. The goal of this study was to identify
      a molecular footprint associated with ongoing versus long term consequences of
      iron deficiency using microarray analysis. Rats were born to iron-deficient
      mothers, and were analyzed at two different ages: 21 days, while weaning and iron
      deficient; and six months, after a five month iron-sufficient recovery period.
      Overall, the data indicate that ongoing iron deficiency impacts multiple
      pathways, whereas the long term consequences of iron deficiency on gene
      expression are more limited. These data suggest that the gene array profiles
      obtained at postnatal day 21 reflect a brain under development in a metabolically
      compromised setting that given appropriate intervention is mostly correctable.
      There are, however, long term consequences to the developmental iron deficiency
      that could underlie the neurological deficits reported for iron deficiency.

PMID- 17447429
TI  - Long lasting effects of infancy iron deficiency--preliminary results.
AB  - The long-term effects of rehabilitated infancy (1 year old) iron deficiency (ID)
      were examined at age 10. The children were examined for the following variables:
      auditory system function, the level of morning cortisol, I.Q. score (WISC-R), and
      behavioral profile. The results indicate that while the former ID children's
      hearing system appears to function well, there was a delay in brain stem
      processing of the auditory signals. In addition, the level of morning cortisol
      was reduced, the general I.Q. scores were lower than the normal group (mainly in
      the performed subtest), and more sleep disturbances and fatigue during day were
      reported. These outcomes are consistent with established reports on the effect of
      iron deficiency on the rate of myelination in selected brain areas during
      critical period of 1 year olds. The findings of increased sleep disturbances and
      lower I.Q. tests require further study.

PMID- 17447430
TI  - Altered regulation of iron transport and storage in Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by the death of dopaminergic neurons in
      the substantia nigra. This neuronal degeneration is associated with a strong
      microglial activation and iron accumulation in the affected brain structures. The
      increased iron content may result from an increased iron penetration into the
      brain parenchyma due to a higher expression of lactoferrin and lactoferrin
      receptors at the level of the blood vessels and dopaminergic neurons in the
      substantia nigra in PD. Iron may also accumulate in microglial cells after
      phagocytosis of dopaminergic neurons. These effects may be reinforced by a lack
      of up-regulation of the iron storage protein ferritin, as suggested by an absence
      of change in iron regulatory protein 1 (IRP-1) control of ferritin mRNA
      translation in PD. Thus, a dysregulation of the labile iron pool may participate
      in the degenerative process affecting dopaminergic neurons in PD.

PMID- 17447431
TI  - Iron dyshomeostasis in Parkinson's disease.
AB  - Owing to its ability to undergo one-electron reactions, iron transforms the mild
      oxidant hydrogen peroxide into hydroxyl radical, one of the most reactive species
      in nature. Deleterious effects of iron accumulation are dramatically evidenced in
      several neurodegenerative diseases. The work of Youdim and collaborators has been
      fundamental in describing the accumulation of iron confined to the substantia
      nigra (SN) in Parkinson's disease (PD) and to clarify iron toxicity pathways and
      oxidative damage in dopaminergic neurons. Nevertheless, how the mechanisms
      involved in normal neuronal iron homeostasis are surpassed, remain largely
      undetermined. How nigral neurons survive or succumb to iron-induced oxidative
      stress are relevant questions both to know about the etiology of the disease and
      to design neuroprotective strategies. In this work, we review the components of
      neural iron homeostasis and we summarize evidence from recent studies aimed to
      unravel the molecular basis of iron accumulation and dyshomeostasis in PD.

PMID- 17447432
TI  - Cerebral oligemia and iron influence in cerebral structures--element of morbus
      parkinson models?
AB  - The consequences of short phases of restricted cerebral blood flow and iron
      enrichment of striatal tissues resulted in an animal model that could correspond
      to the basic features of a model for Parkinson's disease. An automatic and
      computerized hole-board offers simultaneous data on learning and cognitive memory
      capabilities, learning of distinct patterns of distributed food pellets found and
      eaten in a given time, switches between different locations of food in the holes
      and in different layout patterns. Wistar rats after 60 min of bilateral clamping
      of the carotid arteries (BCCA) under pentobarbital anesthesia received 1.5 microg
      FeCl3 injected one week after BCCA unilaterally into the ventrolateral striatum.
      The experiments showed that reduced cerebral blood flow and increased iron within
      the striatal tissue had the effect of retarding reactions. Rats after BCCA and
      iron need 180 s to find pellets deep inside holes that are distributed in a
      distinct pattern. During only 60 or 30s BCCA plus iron rats are no longer able to
      find the same number of pellets as over 180s. Rats after BCCA plus NaCl do not
      show such reduced success. These results point to the idea that cerebral oligemia
      and increased iron in the striatum stimulate the pathological symptoms of
      Parkinson's disease which need also more time to have reaction and success (see
      Fig. 5). The data covering abbreviated time-spans show how heavily the BCCA + Fe
      animals are dependent on longer times.

PMID- 17447433
TI  - Impact of selenium, iron, copper and zinc in on/off Parkinson's patients on L
      dopa therapy.
AB  - We have quantitated CSF and serum levels of Selenium, iron, copper and zinc by
      Atomic absorption spectrophotometer in 36 patients with parkinson's disease all
      on L-dopa therapy. Out of these 19 showed on or positive response to L-dopa where
      as 21 patients showed on and off response. These data were compared with 21
      healthy controls. The results showed that serum levels of iron, copper and zinc
      remained unchanged where as in CSF, significant decrease in zinc was found in
      both on and on/off PD patients indicating the deficiency of zinc which continues
      in the worsening clinical condition of off patients. The level of copper remained
      unchanged in both on and on/off PD patients. Iron and selenium increase in CSF of
      both patients which is a clear evidence of relationship between increased iron
      and selenium level in brain which could be correlated with decrease in dopamine
      levels and oxidative stress in PD Patients.

PMID- 17447434
TI  - Metal specificity of an iron-responsive element in Alzheimer's APP mRNA
      5'untranslated region, tolerance of SH-SY5Y and H4 neural cells to
      desferrioxamine, clioquinol, VK-28, and a piperazine chelator.
AB  - Iron closely regulates the expression of the Alzheimer's Amyloid Precursor
      Protein (APP) gene at the level of message translation by a pathway similar to
      iron control of the translation of the ferritin L- and H mRNAs by Iron-responsive
      Elements in their 5' untranslated regions (5'UTRs). Using transfection based
      assays in SH-SY5Y neuroblastoma cells we tested the relative efficiency by which
      iron, copper and zinc up-regulate IRE activity in the APP 5'UTR. Desferrioxamine
      (high affinity Fe3+ chelator), (ii) clioquinol (low affinity Fe/Cu/Zn chelator),
      (iii) piperazine-1 (oral Fe chelator), (iv) VK-28 (oral Fe chelator), were tested
      for their relative modulation of APP 5' UTR directed translation of a luciferase
      reporter gene. Iron chelation based therapeutic strategies for slowing the
      progression of Alzheimer's disease (and other neurological disorders that
      manifest iron imbalance) are discussed with regard to the relative neural toxic
      action of each chelator in SH-SY5Y cells and in H4 glioblastoma cells.

PMID- 17447435
TI  - Green tea catechins as brain-permeable, non toxic iron chelators to "iron out
      iron" from the brain.
AB  - Evidence to link abnormal metal (iron, copper and zinc) metabolism and handling
      with Parkinson's and Alzheimer's diseases pathology has frequently been reported.
      The capacity of free iron to enhance and promote the generation of toxic reactive
      oxygen radicals has been discussed numerous times. Metal chelation has the
      potential to prevent iron-induced oxidative stress and aggregation of alpha
      synuclein and beta-amyloid peptides. The efficacy of iron chelators depends on
      their ability to penetrate the subcellular compartments and cellular membranes
      where iron dependent free radicals are generated. Thus, natural, non-toxic, brain
      permeable neuroprotective drugs, are preferentially advocated for "ironing out
      iron" from those brain areas where it preferentially accumulates in
      neurodegenerative diseases. This review will discuss the most recent findings
      from in vivo and in vitro studies concerning the transitional metal (iron and
      copper) chelating property of green tea, and its major polyphenol, (-)
      epigallocatechin-3-gallate with respect to their potential for the treatment of
      neurodegenerative diseases.

PMID- 17447436
TI  - Limited-stage small-cell lung cancer: therapeutic options.
AB  - Almost 40% of patients with newly diagnosed small-cell lung cancer (SCLC) have
      disease confined to the ipsilateral hemithorax and within a single radiation
      port, i.e., limited-stage disease. The median survival for this group of patients
      after treatment is approximately 15 months, with one in every four patients
      surviving 2 years. Current optimal treatment consists of chemotherapy with
      platinum/etoposide, given concurrently with thoracic radiation. Surgery may
      represent an option for very early-stage disease, but its added value is
      uncertain. Prophylactic cranial irradiation (PCI) is used for patients with
      limited-stage SCLC who have achieved a complete response following initial
      therapy, as it decreases the risk of brain metastases and provides an overall
      survival benefit. Newer targeted agents are currently being evaluated in this
      disease and hold the promise of improving current outcomes seen in patients with
      early-stage disease.

PMID- 17447437
TI  - Emerging role of immunotherapy in the management of prostate cancer.
AB  - There has been a resurgence of interest in developing noncytotoxic immune
      therapies for patients with either hormone-naive biochemically relapsed post
      primary therapy or castrate metastatic prostate cancer. The rationale for
      developing an immunotherapeutic approach has been based on the overexpression and
      underglycosylation of a wide variety of altered "self" molecules including
      prostate-specific antigen (PSA), acid phosphatase (ACP), prostate stem cell
      antigen (PSCA), and prostate-specific membrane antigen (PSMA), which can serve as
      targets for immune recognition and attack. In addition, such a strategy could
      theoretically make use of the patient's immune system to fight the tumor
      particularly if their disease is of reasonably low volume. A variety of
      immunotherapeutic approaches have been explored through phase I, II, and now
      phase III trials demonstrating that immunologic tolerance could be broken, as
      evidenced by the development of hightiter antibodies and T-cell responses
      specific for the tumor. What appears to be revolutionizing the immunotherapy
      field is the combination of vaccines with cytokines or immune modulators, which
      not only potentiate immune reactivity in vivo but foster dramatic antitumor
      responses. This review explores the challenges now faced in establishing a role
      for immune therapies for prostate cancer treatment.

PMID- 17447438
TI  - Clinical trials in older adults with cancer: past and future.
AB  - The risk of cancer increases with age, and as the U.S. population rapidly ages,
      the number of older adults seeking treatment for cancer is also increasing
      dramatically. However, this growing population of older adults has been
      underrepresented in clinical trials that set the standards for oncology care. In
      addition, most clinical trials conducted to date have not addressed the problems
      that accompany aging, including reduced physiologic reserve, changes in drug
      pharmacokinetics, and the impact of comorbid medical conditions and polypharmacy
      on treatment tolerance. As a result, there are variations in treatment patterns
      between older and younger adults and few evidence-based guidelines accounting for
      the changes in physiology or pharmacokinetics that occur with aging. This article
      examines the demographics of cancer and aging, the barriers to enrollment of
      older adults on clinical trials, and approaches for future trials to address the
      needs of the older patient.

PMID- 17447439
TI  - Imaging tumoral hypoxia: oxygen concentrations and beyond.
AB  - The role of hypoxia as a key determinant of outcome for human cancers has
      encouraged efforts to noninvasively detect and localize regions of poor
      oxygenation in tumors. In this review, we will summarize existing and developing
      techniques for imaging tumoral hypoxia. A brief review of the biology of tumor
      oxygenation and its effect on tumor cells will be provided initially. We will
      then describe existing methods for measurement of tissue oxygenation status. An
      overview of emerging molecular imaging techniques based on radiolabeled hypoxic
      markers such as misonidazole or hypoxia-related genes and proteins will then be
      given, and the usefulness of these approaches toward targeting hypoxia directly
      will be assessed. Finally, we will evaluate the clinical potential of oxygen- and
      molecular-specific techniques for imaging hypoxia, and discuss how these methods
      will individually and collectively advance oncology.

PMID- 17447440
TI  - Looking beyond survival survivorship care is critical to the future of oncology.

PMID- 17447441
TI  - [Causal attribution of discrimination and favoritism in a disadvantaged group].
AB  - Two experiments investigated the hypothesis that the need to protect positive
      self-regards mediates the causal attribution of one's failure to discrimination.
      Female undergraduates read a scenario in which either the participant herself or
      another woman (in-group member) took a job interview. The outcome was depicted
      either as failing (Studies 1 and 2) or passing the interview (Study 2).
      Participants attributed the failure to gender discrimination only when the
      interviewers were unanimously sexists. The attribution to discrimination was
      negatively correlated with the state self-esteem in the social domain. When the
      protagonist was an in-group member, a moderate level of discrimination was
      sufficient to elicit the participant' s discrimination attribution. For the
      positive outcome scenario, the participants were more likely to acknowledge the
      influence of favoritism on their own success than on other's success. These
      results suggest that the unwillingness for attributing a failure to
      discrimination functions for the protection of the self-esteem among the members
      of a disadvantaged group. Implications for the study of coping strategies used by
      victims of discrimination are discussed.

PMID- 17447442
TI  - [Japanese mimetic words "Gitai-go" used to describe personality: classification
      and semantics].
AB  - This study investigated Japanese mimetic words "Gitai-go" that can describe
      personality, through classification based on factor analysis and correlation
      analysis with the Five Factor Personality Questionnaire (FFPQ). Japanese
      participants, mostly undergraduates (344 men and 702 women), were asked to rate
      themselves on a five point scale on each of 120 words. Factor analysis of the
      ratings yielded six groups of words.: "Cowardliness", "Slowness", "Preciseness,"
      "Irritableness", "Candidness," and "Frivolousness". Correlations between these
      ratings and the personality scales were as follows. (1) "Cowardliness" showed a
      positive correlation with Emotionality, and a negative correlation with
      Extroversion. (2) "Preciseness" had a high correlation (r = .70) with Controlling
      and a low positive correlation with Extroversion and Attachment. (3)
      "Irritableness" showed a negative correlation with Attachment and a positive
      correlation with Emotionality. (4) Low negative correlations were observed
      between "Slowness" and Extroversion, "Candidness" and Emotionality, and
      "Frivolousness" and Controlling. The ambiguous but expressive nature of mimetic
      words was discussed in relation to the conceptualizations and descriptions of
      personality used in daily interaction.

PMID- 17447443
TI  - [Reminiscence bump and contents of autobiographical memory in Japanese elders].
AB  - A reminiscence bump is a phenomenon that people typically remember the events
      experienced the ages of 10 and 30 more often than these experienced in other
      period. This paper investigates (I) whether a reminiscence bump is found in
      autobiographical memory in Japanese elders, and (2) the features and content of
      autobiographical memories in general and in the bump. Twenty-five participants
      more than sixty-years old recalled past events using a cue-word method, described
      the content of each memory, dated the event, and rated the features of the memory
      on five scales, i.e., vividness, importance, present self-involvement, past self
      involvement, and frequency of recall. The results showed that although a
      reminiscence bump emerged, memories within the bump did not differ from other
      memories in terms of rated features nor in content. Approximately 50% of
      autobiographical memories were "self-centered", 30% were about "self-other
      relations", and the rest were "other-centered" and "scenes" which did not involve
      people. The results were discussed in relation to theories about the reminiscence
      bump.

PMID- 17447444
TI  - [Role of a graph in constructing situation models during learning from expository
      text: why do graphic aids facilitate learning?].
AB  - This study investigated how graphic aids facilitate learning from text by
      examining what kinds of representations might be constructed when readers read
      either a text containing a line graph or the text only. Undergraduates (n=106)
      read a text concerning digitization. Then, they were asked what they had thought
      about while reading in order to examine whether they constructed graphical mental
      representations. Next, a comprehension test was administrated (pre-test). Next,
      they were shown either part of the text contained a line graph (graph group) or
      part of the text only (text group). Finally, the same test was administrated
      again (post-test). The results showed that when the readers had insufficient
      graphical representations, the graph group performed better on the post-test than
      on the pre-test, but text group did not. In contrast, when readers had elaborate
      graphical representations, there were no differences between the pre-test and the
      post-test for both groups. These findings suggest that graphic aids help readers
      to construct graphical representations, which might comprise the situation models
      that readers build for learning from text.

PMID- 17447445
TI  - [Experimental study of the emotional valence of involuntarily recalled
      autobiographical memories].
AB  - Involuntary recollection of autobiographical memories refers to memories of
      personal experiences that pop into consciousness with no preceding attempts at
      remembering. In a laboratory experiment, we examined the effect of emotional
      valence on the involuntary recollection of autobiographical memories.
      Participants evaluated the familiarity of four words referring to various events
      (cues for autobiographical recollection) and then reported whether they had
      unintentionally recalled past experiences during these evaluations. We
      manipulated the emotional valence (positive/negative) and specificity
      (specific/common) of the cue words. In the specific-event condition, cue words
      for positive events elicited more involuntary memories than those for negative
      events. In addition, the mean frequency of recollection was higher in the
      specific-event condition than that in the common-event condition. These results
      are consistent with studies that used diary methods, which showed a dominance of
      positive events in involuntary recollection of autobiographical memories.

PMID- 17447446
TI  - [Differences in sentence completion test responses based on degree of self
      disclosure].
AB  - Projective tests are considered to uncover unconscious emotions while avoiding
      psychological resistance. However, the results of projective tests may be
      affected by conscious emotions. This study investigates whether self-disclosure,
      which is a conscious factor, affected the results of a sentence completion test
      (SCT), which is a projective test. Eighty-five university students completed a
      questionnaire about their degree of self-disclosure, and a SCT. The results
      showed that low disclosers gave more negative responses on the SCT (such as
      denial responses, physiologically related responses, short responses, and short
      emotional responses) than high disclosers. High disclosers expressed more
      emotions, thoughts and feelings (i.e., opinions, positive emotions, wishes,
      directive disclosure responses, and positive self-images) than low disclosers.
      Although projective tests are assumed to minimize psychological resistance, the
      low disclosers gave more defensive responses on the SCT, and the high disclosers
      exhibited more emotional responses. In summary, self-disclosure, which is a
      conscious factor, affected SCT responses.

PMID- 17447447
TI  - [Analysis of self-assessment of everyday memory using metamemory questionnaires].
AB  - Several metamemory questionnaires have been widely used in psychological research
      with various populations including young or elderly, and clinical or non-clinical
      participants. This study investigates the factor structures in three typical
      metamemory questionnaires. The Everyday Memory Questionnaire (EMQ: 28 items), the
      Cognitive Failures Questionnaire (CFQ: 25 items), and the Memory Ability
      Questionnaire (MAQ: 31 items) were administered to 860 undergraduate students.
      Factor analyses for the data from each questionnaire indicated that the EMQ. the
      CFQ, and the MAQ mainly consisted of five, five, and four factors, respectively.
      A factor analysis was performed on the combined data relating to these 14 factors
      to examine the relatedness among the factors. Three factors were obtained:
      retrospective memory, prospective memory, and memory for person's names. The
      results were discussed in terms of the differences of content and formats of the
      questionnaire.

PMID- 17447448
TI  - [Sweating just before the beginning of handgrip performance].
AB  - Mental sweating plays an important role to make handgrips smooth. This study
      examined the relationship between mental sweating and handgrips focusing on the
      timing of sweat secretion. Five students were instructed to grip a soft ball
      (nine centimeters diameter) as strongly as possible. Electrodermal and sweating
      responses were collected from five seconds before to five seconds after the
      beginning of their handgrips. The results showed that electrodermal responses
      increased one second before the beginning of the handgrip, and that sweating
      responses one second after. These results suggest that sweating responses in
      handgrip performance show a different response pattern from the electrodermal
      responses. Readiness for handgrip performance required for the maximum might
      evoked electrodermal responses before the performance, and this process
      facilitated sweat secretion as the strength of the handgrip reached the maximum.

PMID- 17447449
TI  - [Are facial expressions contagious in the Japanese?].
AB  - Previous studies, mainly with Caucasian samples, have shown that facial
      expressions of emotion are contagious, a phenomenon known as facial mimicry. This
      study examined facial mimicry using a Japanese sample. Participants were shown a
      series of Japanese faces (from Matsumoto and Ekman, 1988) on a computer screen
      expressing "happiness", "sadness", "anger", or "disgust". While viewing the
      facial expressions, electoromyograms (EMG) of the participants' faces were
      recorded to see whether their own facial muscles corresponding to the stimulus
      faces were activated. Consistent with the previous studies using Caucasian
      samples, all four facial expressions were mimicked. The peak time of mimicry of
      angry or happy faces was later, while that of disgusted faces was relatively
      sooner. The potential relation of facial mimicry to "emotional contagion", a
      social phenomenon whereby subjective feelings transfer between people, is
      discussed.

PMID- 17447450
TI  - [Naive theories about the relationship between motives and behaviors].
AB  - People have naive theories about the relationship between motives and behaviors.
      Based on recent developments in attribution theories and negativity bias in
      social perception, we hypothesized that people would associate negative behaviors
      only with negative motives, while they would associate positive behaviors with
      not just positive, but also negative motives. These hypotheses were tested in
      three studies. In Studies 1 and 2, we found that behavioral information
      inconsistent with naive theories was best recalled under conditions with no
      cognitive load. However, this recall advantage dissipated when participants were
      under time pressure during the encoding of the behavioral information. In Study
      3, participants were presented with positive and negative behaviors, and were
      asked to infer the actors' motives from these behaviors. The results showed that
      naive theories guided their inferences: negative motives were likely to be
      inferred from negative behaviors, whereas both negative and positive motives were
      inferred from positive behaviors. Implications for attribution theories and
      negativity bias in social perception are discussed.

PMID- 17447451
TI  - [Antecedent factors of junior high school students' mild delinquency:
      longitudinal study from the first through the second school term].
AB  - This study examined the characteristics typically seen before the start of
      delinquency. Questionnaire surveys were administered twice to 1 524 junior high
      school students, in the first and again in the second school term. Students were
      classified into three groups according to the time when they started engaging in
      delinquent behavior: "experienced" (having engaged in delinquency before the
      first survey: N = 304), "started" (reporting their start of delinquency after the
      first survey: N = 157), and "no experience" (having no experience of delinquency:
      N = 1 063). Comparisons of the three groups showed that the "started" group
      shared the same characteristic factors with the "experienced" group. Compared
      with the "no experience" group, both delinquency groups reported a less intimate
      relationship with their parents, more experience of domestic abuse, less parental
      control, and more conforming behavior with their friends. Also, the "started"
      group showed a sharp change in their degree of enjoyment of school life. Although
      the "started" group reported the same level of school life before starting
      delinquency as the "no experience" group, they reported a lower degree of
      enjoyment, nearly equal with that of the "experienced" group, after starting
      delinquency.

PMID- 17447452
TI  - [Cross-modal links between vision and touch in tactile discrimination of line
      orientation].
AB  - This study examined visuotactile cross-modal interactions in the identification
      of tactile stimuli. In Experiment 1, participants were required to discriminate
      the orientation of tactile target stimuli (line segments with left and right
      diagonal orientations) presented at the tip of the participant's left index
      finger via an Optacon, while trying to ignore a task-irrelevant visual diagonal
      line presented with a 200-ms or 700-ms stimulus onset asynchrony (SOA). The
      results show that the participants responded faster when the orientation of the
      tactile stimuli were congruent with the orientation of the visual stimuli than
      when they were incongruent in the 200-ms SOA condition. To assess at what level
      of processing the reaction time advantage obtained with congruent orientation
      trials takes place, Experiment 2 served as a replication of Experiment 1 with
      somatosensory event-related brain potential (ERP) recordings. ERP effects of
      orientation congruency were observed between 200 and 350 ms post-stimulus,
      suggesting that visuotactile cross-modal interactions may occur at intermediate
      perceptual-cognitive stages rather than at early sensory-specific or late motor
      related stages.

PMID- 17447453
TI  - [Effects of visual features of a weapon on eyewitnesses' cognitive processing].
AB  - This study examines the hypothesis that a knife attracts witnesses' attention
      because of its pointed shape. In Experiment 1, 60 participants were shown a
      picture of a kitchen scene in which a woman held one of three items: a pointed
      knife, a square-shaped knife, or a detergent spray bottle. The weapon focus
      effect was measured by the recognition of details related to the object.
      Recognition information was significantly greater in the pointed knife condition
      than in the other conditions. In Experiment 2,40 participants viewed slides that
      depicted the assembling of a plastic model using either pointed tweezers or
      square-shaped tweezers. As in Experiment 1, participants remembered more details
      in the pointed tweezers condition than the other condition. Both results show
      that visual features of a weapon affect witnesses' memory and suggest that the
      pointed shape of knife is a factor that attracts witnesses' attention.

PMID- 17447454
TI  - [Defensive pessimists and coping: the goodness of fit hypothesis].
AB  - The goodness of fit hypothesis (Lazarus & Folkman, 1984) posits that it is
      adaptive to use emotion-focused coping and not to use problem-focused coping in
      uncontrollable situations. This study examines the coping skills that defensive
      pessimists (DPs) tend to use in uncontrollable situations. The participants were
      282 Japanese college students, from which 61 DPs and 64 strategic optimists (SOs)
      were identified. Based on the controllability they reported about recalled stress
      situations, they were classified into controllable or uncontrollable subgroups.
      Eight coping skills, which are concerned with emotion-focused or problem-focused
      coping, were compared. T-test and analysis of variance (ANOVA) showed that DPs in
      uncontrollable situations tended not to use emotion-focused coping, which is not
      consistent with the goodness of fit hypothesis, but they also tended not to use
      problem-focused coping, which is consistent with the hypothesis. These results
      imply that DPs can control their behavior adaptively so they do not increase
      stress more in uncontrollable situations, although they have a vulnerability to
      feel stress easily because they can not use emotion-focused coping effectively.

PMID- 17447455
TI  - [Factor determining satisfaction with policies regarding disaster wastes: flooded
      areas of cities].
AB  - This study examines the factors that determine satisfaction with the policies
      regarding disaster wastes, focusing specifically on the case of flood. A survey
      was conducted of residents in previously flooded areas of Sanjyo, Fukui, and
      Toyooka. The respondents rated the extent to which the affected administration
      explained things to them, listened to their opinions, damage from the flood, and
      problems with disaster wastes. The results showed that the perception of the
      distance from home to the garbage station determined the satisfaction with the
      policies regarding disaster wastes among the respondents who had less disaster
      wastes. On the other hand, the perception of listening to their opinions
      determined satisfaction with the policies among the respondents who had a lot of
      waste. The findings suggest that the determinant factors are different depending
      upon the situational factors.

PMID- 17447456
TI  - [Analyses of the sensory relevance of adjective pairs by the modality
      differential method].
AB  - We used the newly developed "modality differential" (MD) method to investigate
      the sensory-relevance properties of adjective scales that are widely used in the
      semantic differential (SD) technique. Participants (N = 342) were asked to rate
      the relevance of each of 17-19 adjective pairs, selected from a total 75 pairs
      for ten sensory modalities, using a 7-point scale. We conducted a principal
      component analysis and a cluster analysis on the obtained MD data. We found that
      this data were well explained by the three components or three categories of
      proximal, proprioceptive, and distal-type senses, corresponding to psychological
      classification of sense modalities. In addition, we analyzed the sensory
      relevance properties of the adjective scales that make up the three factors of
      the SD technique. We found that the adjectives of the Evaluation factor can be
      regarded as multi-sensory scales that show generally higher relevance magnitudes
      for multiple modalities. On the other hand, the adjectives making up the Activity
      and Potency factors show high relevance to specific modalities such as
      auditory/kinesthetic and tactile modalities, respectively. We discussed
      differential uses of the MD method for measuring the sensory-relevance of several
      materials such as artworks or industrial products.

PMID- 17447457
TI  - [Predictive power of working memory task for reading comprehension: an
      investigation using reading span test].
AB  - This study investigated the crucial factor mediating a correlation between
      performance of reading span test (RST) and reading comprehension. In the research
      literature on this issue, one of the remaining controversial points is whether
      the similarity of sentence processing between RST and comprehension contributes
      to the correlation. In this study, four RST conditions were created by the
      combination of two factors: relatedness of stimulus sentences (related or
      unrelated with each other) and focus of target words (focus or non-focus with
      respect to sentence meaning). If the correlation is mediated by the similarity of
      sentence processing, RST performance of related and focus condition, which was
      most akin to comprehension, would have higher correlation with reading
      comprehension than other conditions. However, as a result of correlation analysis
      based on data from ninety-six participants, no such evidence was obtained. On the
      other hand, RST performance of unrelated conditions that were supposed to
      strongly require attention control showed significant correlation with reading
      comprehension. These findings are discussed in terms of the contribution of
      attention control and short-term memory to performing RST and reading
      comprehension.

PMID- 17447458
TI  - [Effect of fear on eyewitness' retrieval in recognition memory].
AB  - The effect of fear on the retrieval of eyewitness' recognition memory was
      experimentally investigated. Participants were presented with a thematic series
      of slides of either neutral or ambiguous stimuli. The ambiguous stimulus
      consisted of a red liquid flowing on a girl's head. Participants who saw the
      ambiguous stimulus interpreted the liquid as either red paint, or the girl's
      blood. Differences in the interpretation of the ambiguous stimulus affected the
      participants'recognition memory. Participants who interpreted the stimulus as
      blood displayed inferior memory compared to those who interpreted the stimulus as
      red paint or those who were shown the neutral stimulus. Moreover, when the
      participant's interpretation was changed from blood to red paint by an
      experimenter, the memory for central details was enhanced. These results suggest
      that fear interferes with retrieval. Participants' memory could be improved by
      reducing fear during the retrieval stage.

PMID- 17447459
TI  - [Longitudinal study of the situational specificity of coping strategies].
AB  - This longitudinal study examines the situational specificity of coping strategies
      for 3 943 male employees of the research and development division of an
      industrial company. The Job Stress Scale-Revised version (JSS-R) was administered
      twice to the same subjects 40 months apart to assess chronic job stressors
      (qualitative and quantitative) and coping strategies (problem-solving, support
      seeking, and problem-leaving). Analysis of variance (ANOVA) was used to examine
      changes in coping strategies corresponding to changes in chronic job stressors.
      The results suggest a situational specificity of coping strategies. (a) With
      decreasing qualitative stressors, "problem-solving" coping increases and "problem
      leaving" coping decreases. (b) With increasing qualitative stressors, "problem
      leaving" coping increases and "problem-solving" coping decreases. (c) With
      increasing quantitative stressors, "support-seeking" coping increases. (d) With
      decreasing quantitative stressors, "problem-leaving" coping decreases. (e) There
      is no variance in "problem-leaving" coping attributable to the change in the
      quantitative stressors when the qualitative stressors decrease or increase.
      "Problem-leaving" coping is more strongly related to qualitative than
      quantitative stressors.

PMID- 17447460
TI  - [Effects of direct and indirect exchange on trust of in-group members].
AB  - Yamagishi and colleague showed that behavior favoring the in-group and trust of
      in-group members are based on the expectation of generalized exchange. We
      successfully tested a related prediction that people show stronger trust of in
      group members than of out-group members in the faith game but not in the trust
      game. We argued that the direct exchange aspect inherent in the trust game
      suppresses expectations of generalized exchange taking place in the group. We
      conducted an experiment with 79 Japanese and 83 Australian participants. In the
      trust game, 27 of the 82 participants trusted the in-group trustee, while 29
      trusted the out-group trustee. In the faith game, in which the expectation of
      generalized exchange was intact, 47 of the 80 participants trusted the in-group
      trustee and 37 trusted the out-group trustee. These results support our argument
      that expectations of generalized exchange, not in-group stereotypes, are the
      source of in-group trust. No cultural differences were observed between Japanese
      and Australian participants.

PMID- 17447461
TI  - [Effect of social context on middle-way judgments among the Japanese].
AB  - In an experiment with 141 Japanese participants, we tested an alternative
      interpretation of Peng & Nisbett's (1999) study that examined Chinese
      participants' responses to contradictory statements. They found that differences
      in the plausibility judgments about two contradictory statements were smaller
      when the statements were presented simultaneously than when they were presented
      independently (i.e., middle-way judgment). This pattern was not found among
      Americans. In a partial replication of their experiment, we tested our hypothesis
      that the middle-way judgment responses among Asians are specific to the social
      domain. We compared participants' responses to contradictory statements in two
      conditions. In the social context condition, each statement was expressed as an
      opinion of a particular person. In the non-social context condition, the same
      statement was expressed as a general opinion without mentioning who made the
      statement. The results indicate that social context is required for the middle
      way seeking responses to occur.

PMID- 17447462
TI  - [Autism-spectrum quotient (AQ) Japanese children's version " comparison between
      high-functioning children with autism spectrum disorders and normal controls].
AB  - The Autism-Spectrum Quotient (AQ) children's version has confirmed reliability
      and validity in the UK. In the current study, the children's AQ was administered
      in Japan to investigate whether the UK results are found in a very different
      culture. Two groups of children from primary and secondary schools were assessed:
      Group 1 (n = 81) children with Autism Spectrum Disorders (ASD, including Asperger
      Syndrome and high-functioning autism); Group 2 (n = 372) randomly selected
      controls, age-matched with Group 1. The children with ASD had a mean AQ score of
      31.9 (SD = 6.69), which was significantly higher than controls (mean AQ = 11.7,
      SD = 5.94). Males scored significantly higher than females in the control group,
      but not in the ASD group. The pattern of difference between the Japanese clinical
      group and the control group was remarkably similar to the findings in the UK.

PMID- 17447463
TI  - [Retrieved information in intentionality ratings of other persons' behaviors].
AB  - Participants (N = 153) rated intentionality (with a confidence rating) of 10
      behaviors from the observer's perspective. There were three conditions of
      behaviors: behavior-only, behavior with-reason, or behavior with-cause
      conditions. Significant differences between the means for all of the behavior
      conditions were found for both intentionality and confidence ratings, and
      interactions of Condition x Behavior also significant. When the intentionality
      values were transformed with a V-shaped function, the means of the transformed
      values significantly increased along with the mean confidence rating in the with
      reason and with-cause conditions. In addition, the across-participant
      correlations between intentionality and confidence for each behavior were
      negative when the intentionality mean was near the minimum, and the correlations
      were positive when the intentionality mean was large; this trend was close to a
      linear function. These findings suggest that the intentionality rating was based
      on both a binary judgment and a confidence value.

PMID- 17447464
TI  - [Reliability and validity of the modified Japanese version of the South Oaks
      Gambling Screen (SOGS)].
AB  - The South Oaks Gambling Screen (SOGS) was originally developed to screen for
      pathological gamblers in clinical settings, and its use has been expanded to
      other settings such as prevalence studies of pathological gambling in general
      populations. There are few studies of pathological gambling in Japan, except for
      the two studies on the development of the modified Japanese version of the SOGS.
      The present study examines the reliability and validity of the modified Japanese
      version of the SOGS using two different groups: a university student group (N =
      96) and a gambler group (N = 66). Analyses of the modified Japanese version of
      the SOGS showed that there was sufficient internal consistency (alpha = .898) and
      reliability. The modified Japanese version of the SOGS demonstrated satisfactory
      validity in differentiating the university student group from the gambler group.

PMID- 17447465
TI  - [Active consciousness and the prefrontal cortex: a working-memory approach].
AB  - Biological studies of human consciousness based on recent neuroimaging
      experiments, i.e., functional magnetic resonance imaging (fMRI) and positron
      emission tomography (PET), were reviewed from the viewpoint of different
      functions of consciousness. A biological hierarchy of consciousness structured in
      three levels, i.e., arousal, awareness and self-consciousness, was reviewed in
      connection with working memory. We found that the dorsolateral prefrontal cortex
      (PFC), anterior cingulate cortex, medial PFC, and parieto-temporal junction area
      play a crucial role in social cognition involving estimation of the mental states
      of other people. The ventrolateral PFC plays a role in language-based
      rehearsal/imitation in connection with a mirror system. Frontal pole and
      orbitofrontal areas are also likely to contribute to generation of self function,
      reward expectancy and internal planning of goal-directed behavior. Interestingly,
      we found that these various PFC and related areas strongly contribute to active
      consciousness based on the working memory system. Furthermore, we have shown that
      a theory-of-mind approach could be closely related to higher cognitive functions
      involved in working memory, which has a meta-recognition processes during
      mentalization.

PMID- 17447466
TI  - Role of tyrosine kinase-dependent phosphorylation of NR2B subunit-containing NMDA
      receptor in morphine reward.
AB  - We previously demonstrated that the morphine-induced rewarding effect was
      dramatically suppressed by cotreatment with an NR2B subunit-containing N-methyl-D
      aspartate (NMDA) receptor antagonist ifenprodil. Therefore we propose here that
      the NR2B subunit-containing NMDA receptor may be involved in the rewarding effect
      of morphine. A growing body of evidence indicates that tyrosine kinases, such as
      Src family kinases, increase the phosphorylation of the intracellular C-terminal
      tyrosine residues on the NR2B subunit and potentiate NMDA receptor function. The
      following review provides our recent findings regarding the role of tyrosine
      kinase-dependent phosphorylation of the NR2B subunit-containing NMDA receptor in
      the development of psychological dependence on morphine.

PMID- 17447467
TI  - [Mental health and utilization of mental health services among victims of crime
      in Japan].
AB  - Since the Crime Victims Act became enforced in 2005, the mental health recovery
      of crime victims has become an important issue among national government and
      local authorities. A high prevalence of psychiatric disorders, such as PTSD,
      among crime victims has been reported in domestic and foreign studies. However,
      little is known about the percentage of victims of crime who actually attend
      mental health services. The prevalence of mental health service usage varied from
      one study to another and is thought to be higher among victims of severe crimes,
      such as sexual assault. Several factors associated with seeking mental health
      care, including the presence of psychopathology, appear to be common among the
      studies. To offer suitable mental health services for crime victims, various
      organizations or agencies must cooperate with each other, including the police
      and prosecution, private victim support groups, and medical departments like
      emergency medical care centers and gynecology clinics. This report summarizes
      mental health problems and the use of mental health services among crime victims,
      and discusses how crime victims who require medical treatment may actually
      receive adequate mental health care.

PMID- 17447468
TI  - Saturated and monounsaturated fatty acids increase interleukin-10 production in
      rat hepatocytes.
AB  - Interleukin-10 (IL-10) is a potent anti-inflammatory cytokine, but it still
      remains unknown whether saturated or unsaturated fatty acid affects IL-10
      production in hepatocytes that contribute to lipid metabolism. Primary rat
      hepatocyte cultures were treated with different fatty acids (18:0 stearic acid,
      18:1 oleic acid; 18:2 linoleic acid, 18:3 linolenic acid) at 300 microM for 24
      hours. The concentrations of IL-2, IL-10, GM-CSF and IFN-gamma in the medium were
      detected by multiplex cytokine array. IL-10 was significantly increased with
      treatment of stearic acid and oleic acid. Production of IL-10 by saturated and
      monounsaturated fatty acids in hepatocytes may be one of the reasons why the lard
      oil had less inflammation in the hepatic steatosis animal models.

PMID- 17447469
TI  - [Amount of alcohol intake and carotid ultrasonographic findings in metabolic
      syndrome].

PMID- 17447470
TI  - [Spot diagnosis of infectious exanthema].
AB  - There are lots of infectious diseases accompanied with exanthema. When the
      physicians see the patients with exanthema, they should carefully examine the
      form of exanthema and accessory symptoms. The physicians also should inquire of
      the patients about past history, history of vaccination and situation of current
      infectious disease epidemic in surrounding area. These clinical approaches lead
      to specific diagnosis. On this manuscript, I show the photos of several major
      infectious exanthema caused by viral, bacterial, bacterial toxin and so on.

PMID- 17447471
TI  - [Detection of antibodies by immunoblotting using Chlamydia trachomatis serovars].
AB  - We compared reactivity between Chlamydia serovar antigens and sera from 18
      patients using immunoblotting (IB) and enzyme-linked immunosorbent assay (ELISA).
      The antigens used were Chlamydia trachomatis serovar L2, D, E, and C organisms
      for IB and synthetic peptides derived from C, E, G, and L2-VDIV genes for ELISA.
      Eleven of 12 sera collected from Chlamydia antigen-positive women with cervicitis
      strongly reacted with C. trachomatis serovar E, as did one serum with serovar C
      in immunoblotting profiles. ELISA coated individually with peptides E and C
      strongly reacted with the sera of 6 different patients. The IB result between
      serovar L2, D, E, and C and sera from the 6 other women patients showed
      reactivity at E > or = D > or = L2 > or = C. ELISA using a synthetic peptide
      mixture including C, E, G and L2 peptides gave positive results for all 18 sera.
      These results indicate that IB sensitivity differes with the C. trachomatis
      serovar antigen used and that certain cases may produce inconsistent results
      between IB and ELISA. Results of ELISA and IB are thus not always consistent,
      indicating that different synthetic peptides should be used in ELISA for
      detecting of low-level C. trachomatis antibodies.

PMID- 17447472
TI  - [Distribution of thermostable direct hemolysin (TDH)- and TDH-related hemolysin
      (TRH)-producing Vibrio parahaemolyticus in coastal Shimane Prefecture and TDH and
      TRH V parahaemolyticus contamination of retail shellfish].
AB  - We studied distribution of thermostable direct hemolysin (TDH)- and TDH-related
      hemolysin (TRH)-producing Vibrio parahaemolyticus in coastal sea water, sediment,
      and shellfish and related retail shellfish contamination in Shimane Prefecture,
      Japan, between 2002 and 2004. V. parahaemolyticus was isolated from > 80% of sea
      water, sediment, and shellfish. The detection of TDH gene (tdh) and TRH gene
      (trh)-positive V parahaemolyticus in sea water was 11%, in sediment 16%, and in
      shellfish 26%. The number of genes and gene-related in seawater was 23 MPN/L, in
      sediment 29 MPN/100 g, and in shellfish 460 MPN/10 g. TDH- and TRH-producing V.
      parahaemolyticus detected in seawater was 5%, in sediment 11% and in shellfish
      14%. The continuous distribution of TDH-producing O2:K28, O4:K88, O4:K37, and
      O4:KUT organisms on the western coast and TRH2-producing O5:k30, O5:K43, O10:K19,
      O10:KUT, O11:K40, O11:KUT, and OUT:KUT organisms on the Oki Island coast
      suggested the settlement of these organisms in these coastal environments. From 7
      (12%) of 59 retail short-necked clam samples, we isolated TDH-producing O 1:KUT,
      O3:K6 (2 strains from 2 samples imported from Korea), O4:K12, OUT:K8, and TRH2
      producing OUT:K40 and OUT:K51 organisms. These findings suggested that TDH- and
      TRH-producing V. parahaemolyticus are widely distributed along the coast of this
      prefecture and are transported by contaminated retail shellfish from other areas.

PMID- 17447473
TI  - [Utility and limitation of the rapid IgM antibody detection test for the
      diagnosis of Mycoplasma pneumoniae infection].
AB  - I evaluated performance of the Mycoplasma pneumoniae-specific IgM antibody rapid
      detection test (ImmunoCard Mycoplasma, IC, Meridian, USA) and compared it to the
      particle agglutination (PA) test and ELISA tests (Mycoplasma pneumoniae IgG, IgA,
      IgM ELISA medac, Medac Diagnostika, Germany). Serum samples numbering 112 were
      obtained from 70 pediatric patients (< 16 years old) with M. pneumoniae infection
      diagnosed by a PA test (four-fold or greater rise by paired serum samples or > or
      = 1:640 by a single serum sample). Of these, 82 samples (73.2%) were positive in
      IC and 91 (81.3%) positive in ELISA IgM tests. Specifically, for samples obtained
      within 7 days following the onset of fever, 6 of the 14 positive in the ELISA IgM
      test were negative in IC and 4 of the 18 samples negative in the ELISA IgM test
      were positive in IC. I ascribed this difference to the difference in antigens
      used in each test. In the analysis of sequential serum samples from 2 patients
      with M. pneumoniae pneumonia, IC was still positive in 248- and 527-day samples
      for which a PA test and the ELISA IgM and IgG tests indicated no acute infection.
      Nine (36.0%) of 25 serum samples obtained from apparently healthy adult
      volunteers were positive in IC. Of the 9 IC-positive cases, ELISA tests suggested
      possible recent infection at most in 3 cases, while the remaining 6 cases had no
      evidence of acute infection. In conclusion, although IC is sufficiently sensitive
      as a rapid screening test for detecting M. pneumoniae-specific IgM antibody, a
      positive result in the test does not always indicate acute infection by this
      organism. To ensure accurate diagnosis of M. pneumoniae infection, paired serum
      samples are thus required for conventional methodologies.

PMID- 17447475
TI  - [Preliminary trial of syndromic surveillance to early detection of nosocomial
      infection outbreak].
AB  - OBJECTIVE: To detect nosocomial outbreaks early we construct syndromic
      surveillance for inpatients with fever, respiratory symptoms, diarrhea, vomiting,
      or rash and evaluate it statistically. METHODS AND MATERIALS: In hospital using
      electronic medical records since August 1999, we studied the number of inpatients
      with a certain symptoms from 1999 to 2005. To prospectively detect outbreaks
      after January 1, 2005, we first estimated the baseline using data from August 1,
      1999 to the day before any given day. We then predicted the number of patients on
      the day and judge whether an outbreak has occurred, evaluating this by checking
      it sensitivity and specificity to detect outbreaks other than those with previous
      patterns. RESULTS: From August 1999 to December 2005, 115,532 patients had fever,
      126,443 respiratory symptoms, 87,923 diarrhea, 32,858 vomiting, and 11,212 In
      2005, in prospective detection, 23,617 had fever, 23,698 respiratory symptoms,
      14,671 diarrhea, 5,893 vomiting, and 2,486 rash. DISCUSSION: This hospital had a
      nosocomial Noro virus outbreak on January 27, 2005. Syndromic surveillance
      identified an outbreak of vomiting at a 0.1% criterion. Our system thus detects
      nosocomial outbreaks and is of practical use. The next step will be ward-by-ward
      examination, after which we will experiment with rapid information collection,
      analysis, reports of results, and investigation by infection control teams.

PMID- 17447474
TI  - [The risk of pertussis and diphtheria infections among pediatric healthcare
      workers in Japan].
AB  - For infection control in pediatric hospitals, we investigated the risk of
      pertussis and diphtheria infections among pediatric healthcare workers. Forty
      nine Japanese pediatric healthcare workers in 12 general hospitals were screened
      for antibodies of pertussis toxin (PT), filamentous hemagglutinin (FHA), and
      diphtheria toxin (DT). The seropositive rates of anti-PT IgG (protective level, >
      10 U/mL), anti-FHA IgG (> 10 U/ mL), and anti-DT (> 0.11 U/mL) were 50, 82, and
      59%, respectively. During this survey period (Oct. 2003-Feb. 2004), 16 (33%) of
      the healthcare workers were in contact with pertussis-infant (s). However, all
      culture and PCR tests for Bordetella pertussis were negative. One of the 16
      exposed healthcare workers, a male pediatrician, had serological evidence of a
      pertussis infection, but no disease symptomatic of pertussis. Our observations
      indicate that i) 50 and 41% of Japanese pediatric healthcare workers were
      seronegative for pertussis (anti-PT IgG) and diphtheria antibodies, respectively,
      and ii) although the healthcare workers had a high rate of contact with pertussis
      infant (s), the infection rate was low. For pertussis and diphtheria infection
      control in pediatric hospitals, it is important for healthcare workers to be
      aware of their own protection levels against these diseases.

PMID- 17447476
TI  - [Largest outbreak of legionellosis associated with spa baths: comparison of
      diagnostic tests].
AB  - In July 2002, a large outbreak of legionellosis occurred in a bathhouse with spa
      facilities in Miyazaki Prefecture. Among the visitors, 295, including suspected
      cases had pneumonia and/or symptoms of fever, coughing, etc. Of these, 37% were
      hospitalized and 7 died. Clinical samples from 95 mainly inpatients were
      collected and microbiologically tested at our laboratory. Legionella pneumophila
      serogroup (SG) 1 was isolated from 3 of 24 in sputum culture, and none of the 3
      had been treated effectively with antibiotics at sputa collection. L. pneumophila
      antigen in urine was detected by using enzyme immunoassay and/or
      immunochromatographic kits in 23 of 75 patients. Serum antibodies to L.
      pneumophila SG1 and Legionella dumoffii were detected in 5 each of 66 patients--9
      cases including a case at mixed infection-by microplate agglutination test and/or
      indirect immunofluorescence assay. At our laboratory, 32 were diagnosed with
      legionellosis. In this outbreak, 14 were diagnosed at other laboratories,
      resulting in 46 confirmed cases. Urine antigen was detected more frequently by
      Binax NOW immunochromatographic assay than by Biotest EIA-31% versus 16% of cases
      tested. Both assays detected urine antigen only in samples collected within 4
      weeks after onset. Antigen concentration in urine enhanced sensitivity-58% and
      51%-and extended the period of antigen detection beyond 5 weeks. Both antibody
      titers to L. pneumophila SG1 and L. dumoffii in more than 90% of sera collected
      within 3 weeks after onset were < 1:16. The rate of serum antibody titer to > or
      = 1:128 within 3 weeks was 1.6%, during 4 to 6 weeks less than 10%, and after 7
      weeks or more 8 to 25%. After an administrative report was published, L.
      pneumophila DNA in sputa was detected in 5 of 17 patients by nested PCR,
      resulting in extra 3 cases. Altogether, urinary antigen detection and PCR were
      more effective in laboratory diagnostic tests than culture and serology. Culture
      combined with molecular epidemiology is critical, however, for confirming the
      source of infection.

PMID- 17447477
TI  - [Nosocomial infection caused by multidrug-resistant Staphylococcus aureus with
      reduced susceptibility to vancomycin and teicoplanin.--Yamagata Prefecture,
      Japan; May 2004-Jun 2005].
AB  - Nosocomial infection caused by methicillin-resistant Staphylococcus aureus (MRSA)
      occurred at a major in Yamagata prefecture hospital between May 2004 and June
      2005. We studied pulsed-field gel electrophoresis patterns, antimicrobial
      susceptibility patterns, and bacteriological features, such as coaglase type for
      eight isolates, including two of methicillin-resistant Staphylococcus epidermidis
      (MRSE). Our results suggest that this case was caused by a single strain of
      multidrug-resistant S. aureus. These 8 clinical isolates indicated reduced
      susceptibility to vancomycin and teicoplanin. PCR assay results for detection of
      the staphylococcal vanA, vanB, and vanC gene were all negative as all isolates.
      In transmission electron microscopy, cell walls appeared thicker than those of a
      susceptible strain from food poisoning. MRSA with reduced susceptibility to
      glycopeptide antibiotics may not be treated successfully with vancomycin or
      teicoplanin, making it important to closely observe MRSA with reduced
      susceptibility to glycopeptide antibiotics.

PMID- 17447478
TI  - [A case of Munchausen syndrome with recurrent bacteremia and PR3-ANCA
      positivity].
AB  - A 29-year-old woman chiropractor with repeated episodes of bacteremia and
      positive for cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) and
      antiproteinase-3 (PR3) antibody had an 11-year history of asthma and repeated
      hospitalization. While hospitalized she developed a spiking nocturnal fever with
      chills and erythema of the lower leg. Her fever resolved spontaneously, but
      corticosteroid therapy and antibiotics did not effectively reduce her symptoms.
      Plain X-ray film and CT showed pulmonary changes, and lung biopsy granulomas
      without vasculitis. Immunological studies showed a positive PR3-ANCA (c-ANCA)
      test, and skin biopsy of the crural erythema showed foreign body granuloma.
      Multiple blood cultures were positive for several strains of bacteria, including
      Fusobacterium necrophurum, Mycobacterium fortuitum, and Clostridium species. When
      placed in a single room and monitored, she did not develop new fever or erythema.
      Because self-injury was assumed, she was diagnosed as having Munchausen syndrome.
      This is, to our knowledge, the first report of Munchausen syndrome with PR3-ANCA
      positivity. In patients with repeated infections, the possibility of self-injury,
      the development of PR3-ANCA positivity, and pulmonary granuloma with a disease
      profile similar to vasculitis syndrome should be considered in the definitive
      diagnosis.

PMID- 17447479
TI  - [Purpura fulminans due to pneumococcal pneumonia in a healthy adult: a case
      report].
AB  - We report a case of infectious purpura fulminans due to pneumococcal pneumonia in
      a 61-year-old man presenting multiple organ failure and pneumococcal bacteremia
      secondary to pneumonia on admission. His lower limbs showed rapidly progressive
      purpura and symmetrical dry gangrene. He had no history of or apparent
      immunodeficiency, including asplenia, in abdominal ultrasonography. Despite of
      therapy, he died on day 15 after admission. Infectious purpura fulminans involves
      skin lesions with severe infection often accompanied by disseminated
      intravascular coagulation and septic shock. Although it occurs mainly in
      childhood, especially as a complication of Neisseria meningitis or Varicella
      virus infection, it has also been reported in adult, as a rare complication of
      invasive pneumococcal infection. Most had immunodeficiency such as asplenia or
      postsplenectomy. Purpura fulminans in a previously healthy adult is very rare and
      this is insofar as we know, the first report in Japan detailing the development
      from pneumococcal pneumonia.

PMID- 17447480
TI  - [Voriconazole as an effective therapy against pulmonary aspergillosis in a man
      with immunodeficiency virus-infection: a case report].
AB  - A 45-year-old homosexual man with pneumocystis pneumonia and esophageal
      candidiasis tested positive in ELISA and Western blot analysis for HIV-1. His
      CD4+ T cell count was 43/microL and his HIV-RNA load was 250,000 copies/mL. He
      was treated with Trimetoprim-Sulfamethoxazole, Prednisolone and Fluconazole.
      Valganciclovir was added to treat CMV retinitis. During the clinical course, 21
      days after admission, the patient presented with a temperature of 39 degrees C
      and blood analysis showed neutropenia. Cefepime and G-CSF were initiated, but new
      consolidation was observed in the upper left lobe in chest radiography. He
      underwent bronchoscopy and lavage culture was positive for Aspergillus fumigatus.
      Serum testing of galactomannan was also positive and pulmonary aspergillosis was
      diagnosed. The patient was initially treated with Micafungin but switched to
      Voriconazole when clinical symptoms worsened. An eventual clinical response was
      observed and pulmonary aspergillosis was controlled. Unfortunately, he died of
      sepsis due to MRSA 2 months later. Pulmonary aspergillosis is a devastating
      complication with poor prognosis in patients with HIV infection. Amphotericin-B
      has been the mainstay of pulmonary aspergillosis treatment, but reports indicate
      mortality exceeding 80%. Use of Voriconazole, a relatively new antifungal agent,
      may lower mortality with fewer adverse effects than conventional antifungal
      therapy.

PMID- 17447481
TI  - [Pediatric pneumonia, pleural effusion, and pericarditis following cat scratch
      disease and serological cross-reactions among Bartonella henselae and Rickettsia
      japonica determined by indirect fluorescence antibodies].
AB  - Cat scratch disease is associated with a variety of systemic manifestations. We
      report a pediatric case associated with pneumonia, pleural effusion, and
      pericarditis. A 3-year-old boy developed prolonged fever unresponsive to
      antibiotic treatment, including azithromycin and minocycline. Although the fever
      resolved with corticosteroid treatment, Bartonella henselae IgG titer was
      positive in indirect fluorescence antibodies, as was Rickettsia japonica IgG
      titer. Both titers were significantly reduced by serum absorption with B.
      henselae antigens, and we observed a serological cross-reaction between B.
      henselae and R. japonica.

PMID- 17447483
TI  - Evaluation of lower urinary tract symptoms and how bothersome it was with or
      without urinary incontinence in apparently healthy persons of both sexes.
AB  - We evaluated the effect of urinary incontinence on the degree of being bothersome
      in apparently healthy males and females by a questionnaire survery. From March to
      May, 2003 apparently healthy subjects underwent multiphasic health screening
      after informed of the nature of this study and were asked to fill out the
      questionnaires of International Prostate Symptom Score (IPSS) with IPSS QOL index
      (IPSS-QI) and the short form version of the Urogenital Distress Inventory (UDI
      6). The data were subjected to analytical studies. Of the 388 participants who
      responded completely to both questionnaires, 172 (44.3%) had urinary
      incontinence; 143 were women (36.9%) and 29 men (7.5%). The mean age of the women
      was 46.0 years (range 18.0 to 76.0) and that of men was 47.5 years (range 22.0 to
      76.0). Compared with continent participants, women and men with mixed urinary
      incontinence had a significantly higher IPSS severity (P = 0.0002 and P = 0.0014,
      respectively). In terms of contribution on QOL impairment, the women and men with
      mixed urinary incontinence considered it significantly more bothersome compared
      with continent participants (P = 0.0004 and P = 0.0003, respectively). These data
      showed that urinary incontinence was relatively common among apparently healthy
      women, but not men, and type of incontinence had a different impact on the degree
      of being bothersome in both sexes.

PMID- 17447482
TI  - [Experience with implanted venous reservoirs in patients with terminal urological
      cancers].
AB  - The medical records of 8 consecutive patients with terminal urological cancers
      who were treated with implanted venous reservoirs between October 2001 and July
      2004 were retrospectively reviewed. All 8 devices were placed safely in the 8
      patients, and fluids and drugs were easily administered via the reservoirs. The
      devices were utilized for a mean of 40.6 days (range, 18 to 98) until the
      patients died of the cancer, and there were no complications which required
      removal of the devices such as catheter or reservoir infections, catheter
      occlusions and catheter thromboses. Seven patients were discharged or stayed at
      home on weekends and received home parental nutrition (HPN) through implanted
      venous reservoirs. Although HPN with the implanted venous reservoir is recently
      becoming common in digestive surgery or gynecological fields, it still remains
      uncommon in the urological field. Because this device would be useful and safe
      for patients with terminal urological cancers, we should consider the use of
      implanted venous reservoirs for patients who desire terminal home care.

PMID- 17447484
TI  - [Testicular metastasis and local recurrence of renal cell carcinoma after nephron
      sparing surgery in von Hippel-Lindau disease].
AB  - Bilateral nephron-sparing surgery was performed on a 56-year-old man with von
      Hippel-Lindau disease as initial therapy for renal cell carcinoma (RCC). Two
      years after the surgery, an abdominal computerized tomography (CT) scan revealed
      local recurrence of RCC. The patient was admitted to our hospital after another
      CT scan three years later that indicated aggravation of the cancer. On physical
      examination, he complained of swelling of the scrotum. The patient was diagnosed
      with an intra-scrotal malignant tumor and local recurrence of RCC. We performed
      high orchiectomy and nephrectomy. The testicular tumor was diagnosed as
      testicular metastasis of RCC on pathological examination.

PMID- 17447485
TI  - [Huge retroperitoneal leiomyosarcoma: a case report].
AB  - This is a case report of retroperitoneal leiomyosarcoma in a 61-year-old woman.
      She presented with a chief complaint of back pain. Computed tomography showed a
      left huge retroperitoneal tumor. The tumor was removed with left nephrectomy and
      left hemi-colectomy. Histological examination demonstrated leiomyosarcoma 26 x 20
      x 16 cm in diameter and, 3.84 kg in weight. She died of local recurrence causing
      ileus 2 months after the surgery. Fifty-four cases of retroperitoneal
      leiomyosarcoma including the present case in the Japanese literature are
      reviewed.

PMID- 17447486
TI  - A case of retroperitoneal bronchogenic cyst treated by laparoscopic surgery.
AB  - We describe herein a rare case of a retroperitoneal bronchogenic cyst
      successfully treated by laparoscopic surgery. A 39-year-old man with low-grade
      fever was referred to our hospital because of suspicion of an adrenal tumor.
      Abdominal computerized tomography (CT) and ultrasonography revealed a homogenous
      solid mass, 35 x 30 mm in diameter, in the left suprarenal region. Laboratory
      studies showed that the levels of adrenal hormones were normal except for the
      white blood cell count of 9,700/microL and C-reactive protein of 1.7 mg/dl. We
      diagnosed it as a non-functioning adrenocortical adenoma or an adrenal cyst.
      However, one year later he underwent laparoscopic surgery because the mass had
      gradually increased by 10 mm and the low-grade fever persisted. Pathological
      evaluation of the surgical specimens established the diagnosis of retroperitoneal
      bronchogenic cyst. The low-grade fever disappeared after the surgery.

PMID- 17447487
TI  - [Papillary adenocarcinoma in a seminal vesicle cyst associated with contralateral
      renal agenesis: a case report].
AB  - We report a case of papillary adenocarcinoma inside a seminal vesicle cyst
      associated with contralateral renal agenesis in a 30-year-old man. Coexistence of
      a seminal vesicle cyst and tumors is rare. Surgical excision was performed but he
      died due to liver metastases one year later.

PMID- 17447488
TI  - [Superficial bladder cancer with lung metastasis without local invasion: a case
      report].
AB  - A 66-year-old woman presented with a coin-size lesion in the right lung.
      Bronchoalveolar lavage cytology showed class V. Thoracoscopic partial
      pneumonectomy of right upper lobe was performed and pathologic finding was
      metastatic transitional cell carcinoma (TCC). She had a history of superficial
      bladder tumors which were treated with transurethral resection (TURBT). All
      pathologic findings demonstrated low grade superficial TCC. After the
      pneumonectomy, recurrent tumors were detected in the bladder after three months'
      follow up. Intravesical instillations and TURBT were performed and the pathologic
      finding showed superficial TCC. There have been no signs of recurrence during the
      six-year follow up. The case reported here is of superficial cancer with a
      metastatic lesion in the lung without local invasion in the urinary bladder.

PMID- 17447489
TI  - [A pediatric case diagnosed as urachal cyst and vesicoureteral reflux by urinary
      tract infection: a case report].
AB  - A one-month-old girl was refereed to our department because of urinary tract
      infection. Ultrasonography showed grade III left hydronephrosis and cystic mass
      at the dome of the urinary bladder. Voiding cystourethrography revealed grade 4
      vesicoureteral reflux associated with Hutch's diverticulum. In addition, magnetic
      resonance imaging revealed multiple cysts at the dome of the urinary bladder. The
      vesicoureteral reflux was repaired and the urachal cyst removed.

PMID- 17447490
TI  - [Parastomal hernia with incarcerated necrosis at ascending colon 18 years after
      the construction of ileal conduit: a case report].
AB  - A 78-year-old woman had undergone radical cystectomy and construction of ileal
      conduit because of bladder cancer in 1988. Eighteen years after the operation,
      she was referred to our hospital with the chief complaint of abdominal pain and
      oliguria. She had a mass just superolateral to the stoma with tenderness and
      reddish skin. Abdominal X-ray and computed tomographic scanning showed free air
      and peristomal intestinal dilation in the subcutaneous area. With a diagnosis of
      incarcerated parastomal hernia and intestinal perforation, emergency operation
      was performed. The orifice of the hernia was located in the superolateral aspect
      of the stoma. The ascending colon was locally necrotic and perforated. Usually,
      the orifice of parastomal hernia is so wide that incarceration rarely occurs.
      Parastomal hernia treated with emergency operation is rare, with only 9 cases,
      including our case, reported in the Japanese literature. Three cases had ileal
      conduit, and the content of the hernia was the ascending colon only in our case.

PMID- 17447491
TI  - [Vesicovaginal fistula after sexual intercourse: a case report].
AB  - A 53-year old female visited our hospital with a complaint of continuous urinary
      incontinence after sexual intercourse. She had been diagnosed with carcinoma of
      uterine cervix stage I b2 and had undergone radical hysterectomy and radiation
      therapy (45 Gy). Cystoscopy revealed vesicovaginal fistula in the trigone which
      measured almost 3 cm. We repaired it by transabdominal and vaginal routes 5 days
      after the injury. She was discharged with a Foley catheter. Three months after
      the operation, cystography revealed improvement of vesicovaginal fistula.

PMID- 17447492
TI  - A case of orbital metastasis from prostatic carcinoma as an initial symptom.
AB  - Orbital metastasis caused by prostate cancer is rare. We report a case of
      prostate cancer diagnosed from the initial ocular signs with complaints of
      decreased vision and exophthalmos. The orbital tumor was surgically removed and
      endocrine therapy was performed subsequently. Metastatic carcinoma of the
      prostate should be considered in the elderly male with exophthalmos.

PMID- 17447493
TI  - [Proposal for cell-free biology].

PMID- 17447494
TI  - [PURE technology for protein production].

PMID- 17447495
TI  - [Molecular mechanism of trans-translation].

PMID- 17447496
TI  - [Cell-free translation and tRNA maturation].

PMID- 17447497
TI  - [Wheat germ cell-free protein synthesis].

PMID- 17447498
TI  - [Development and application of evolutionary molecular engineering systems using
      cell-free protein synthesis].

PMID- 17447499
TI  - [Incorporation of nonnatural amino acids into proteins in cell-free translation
      systems].

PMID- 17447500
TI  - [Molecular mechanisms underlying membrane protein integrations in E. coli].

PMID- 17447501
TI  - [Efficient protein NMR analyses by using cell-free protein synthesis system].

PMID- 17447502
TI  - [Expectation for the cell-free synthesis of the multisubunit complex towards the
      three-dimensional structure determination].

PMID- 17447503
TI  - [Development of a high-throughput biochemical annotation method of genetic
      information based on cell-free protein synthesis, and its application to protein
      biology].

PMID- 17447504
TI  - [Exploration of collagen disease-related proteins based on pathogenomics:
      application of a cell-free protein synthesis system ].

PMID- 17447505
TI  - Management of vital organ malperfusion in acute aortic dissection: proposal of a
      mechanism-specific approach.
AB  - OBJECTIVE: We report our strategy for malperfusion accompanying acute aortic
      dissection, especially that involving the abdominal organs, which is based on the
      mechanism and includes percutaneous management. METHODS: From 1991 through
      October 2005, a total of 38 of 135 (28%) patients with acute dissection presented
      with organ malperfusion. Altogether, 31 had type A dissection. The involved
      vascular territories were coronary in 8, brain in 16, celiac and superior
      mesenteric in 6, renal in 10, and lower limb in 13. For the abdominal organs, the
      mechanisms of the malperfusion were classified into the aortic type (n = 3) and
      the branch type (n = 13). The branch type was further divided into the orifice
      type (n = 8) and distal type (n = 5). All but one patient with type A dissection
      underwent a central aortic operation with resection of the entry site.
      Revascularization of the ischemic organ was added by bypass grafting or direct
      reconstruction. Distal organ malperfusion accompanying type B dissection was
      treated by the mechanism-specific approach. That is, the aortic type was treated
      by surgical fenestration, whereas the branch type was treated by percutaneous
      stenting. RESULTS: The one hospital death (2.6%) was due to brain infarction.
      Although a central aortic operation alone successfully reversed aortic-type
      malperfusion in all three patients, it was not effective for branch-type
      malperfusion in five of six vascular territories. Surgical fenestration did not
      successfully reverse branch-type renal malperfusion in two patients. Percutaneous
      stenting was successful in all three vessels with branch-type malperfusion.
      CONCLUSION: Central aortic operation or fenestration is effective for aortic-type
      malperfusion, whereas the branch type may require stenting or bypass grafting.

PMID- 17447506
TI  - Long-term experience with the Sorin Bicarbon and Edwards Mira mechanical valve
      prostheses in the mitral position.
AB  - OBJECTIVE: Sorin Bicarbon (SB) and Edwards Mira (EM) valves have an identical
      mechanical design but different sewing cuffs. The purpose of this retrospective
      study was to analyze the long-term clinical and echocardiographic outcomes after
      mitral valve replacement with these two valves in a combined population of
      patients. METHODS: We retrospectively reviewed records of 73 patients who
      underwent mitral valve replacement using SB (n = 19) or EM (n = 54) valves.
      Preoperatively, 49 patients (68.1%) were in New York Heart Association (NYHA)
      functional class III or IV. Concomitant procedures were performed in 52 patients
      (71.2%). Early and late postoperative echocardiography was performed in 69 and 57
      patients, respectively. RESULTS: Operative mortality was 4.1%, and early
      morbidity was 9.6%. Overall patient survival at 9 years was 85.1% +/- 4.8%.
      Actuarial freedom from valve-related death was 95.4% +/- 2.6% at 9 years. As
      shown by Doppler echocardiography, the early and late mean transprosthetic
      pressure gradients were 3.4 +/- 1.4 mmHg and 3.8 +/- 2.1 mmHg, respectively. At
      the end of follow-up, 98.4% of survivors were in NYHA class I or II. CONCLUSION:
      The Sorin Bicarbon and, Edwards Mira mechanical valves in the mitral position
      provide satisfactory long-term clinical and echocardiographic performance.

PMID- 17447507
TI  - Healing of wound sutures on the mitral valve: an experimental study.
AB  - OBJECTIVE: The aim of this study was to examine the histopathological changes
      that occur during the heading process of a sutured wound on the mitral valve.
      METHODS: In 12 mongrel dogs, an incision was made at a right angle to the annulus
      at the center of the free edge of the anterior mitral leaflet and then sutured.
      Animals were killed 2-16 weeks later and the wounds were examined histologically.
      RESULTS: Two weeks after the operation, fibrin thrombi were found on the atrial
      surfaces of the wound, and organized thrombi became part of the neointima
      thereafter. There were capillaries in the thrombi, but only a few extended from
      the valvular ring. On the ventricular surfaces, fibrous neointima extending from
      adjacent intima without capillary proliferation covered the wound at 2 weeks.
      These heading processes started from the valvular ring side of the wound.
      Processes were delayed near the free edge area, and myxomatous granulation tissue
      extended from the adjacent spongiosa. There were abundant collagen fibers
      obscuring the suture line at 4 weeks in the basal region and at 12-16 weeks near
      the free edge. Calcified deposits with cartilage were found in a thick scar in
      the basal region at 4 weeks and extended to the central area thereafter.
      CONCLUSION: The healing of mitral valvular wounds is slow, especially near the
      free edge area. The wound is covered by organized thrombi at the atrial surface
      and by fibrous sheaths at the ventricular surface. These processes should be
      taken into consideration during the patients' care after valvoplasty, especially
      during the first several months after surgery.

PMID- 17447508
TI  - Tetralogy of Fallot in teenagers and adults: surgical experience and follow-up.
AB  - OBJECTIVE: The aim of this study was to review short- and long-term outcomes
      following total correction in patients with tetralogy of Fallot that presented
      during adulthood. METHODS: It was a retrospective analysis of 284 patients (aged
      14-50 years, mean 19.4 +/- 2.5 years) with tetralogy of Fallot who underwent
      total correction at our institution between January 1991 and December 2001.
      Thirty patients were subjected to postoperative first-pass radionuclide
      angiocardiography scans. A Hindi version of the standard World Health
      Organization quality of life proforma was mailed to 120 patients operated on
      during the first half of the study period. RESULTS: Altogether, 45 (15.8%)
      patients had palliative shunts, and 32 (11%) had preoperative coil embolization.
      The transatrial/transpulmonary artery approach was used in 62 (22%) patients, the
      transventricular approach in 86 (30%) patients, and a combined approach in 136
      (48%) patients. A transannular pericardial patch was used in 200 (70%) patients.
      A total of 61 (21%) patients had nonfatal complications. There were 28 hospital
      deaths. Follow-up ranged from 1 month to 10 years (mean 4.6 +/- 2.3 years). There
      were 7 (2.5%) late deaths and 6 (2.1%) reoperations. Altogether, 94% of patients
      were in New Yk Heart Association (NYHA) class I. Radionuclide angiocardiography
      showed normal right ventricular and left ventricular function in 18 (60%) and 22
      (73%) patients, respectively. All of the 66 respondents perceived an improved
      quality of life. The actuarial survival and freedom from reoperation at 10 years
      were 82.88% +/- 3.80% and 92.82% +/- 3.40%, respectively. CONCLUSION: Total
      correction in this subset of patients offers the best option for long-term
      symptom-free survival.

PMID- 17447509
TI  - Early recurrence of completely resected N2-positive non-small-cell lung cancer.
AB  - OBJECTIVE: Postoperative early recurrence, defined as recurrence within 1 year
      postoperatively, is often experienced with completely resected N2 disease. In
      this study, we evaluated the risk factors for early recurrence with completely
      resected N2 disease. METHODS: . Potential risk factors for postoperative early
      recurrence were evaluated in 75 patients with N2 disease who underwent complete
      resection without any preoperative therapy. Prognostic significance was
      determined by univariate and multivariate analyses. RESULTS: The median follow-up
      period was 24 months, and the 5-year survival rate was 23%. Thirty-nine patients
      developed postoperative early recurrence. The 1-, 3-, and 5-year survival rates
      of patients with early recurrence were 64%, 10%, and 5%, respectively, and 100%,
      51%, and 34%, respectively (p < 0.001). Multistation N1 metastasis was a risk
      factor for postoperative early recurrence by univariate analysis and an
      independent risk factor by multivariate analysis. CONCLUSIONS: Early recurrence
      is a significant poor prognostic factor for completely resected N2 disease. It is
      suggested that the number of N1 stations with metastasis is a risk factor for
      early recurrence and a poor prognostic factor in N2 disease.

PMID- 17447510
TI  - Prospective analysis of depression and psychological distress before and after
      surgical resection of lung cancer.
AB  - OBJECTIVES: The psychological effects of surgery have received little attention
      in patients with lung cancer, so it is unclear how much psychological support is
      required by these patients. This study was done to assess the mental state of
      patients with lung cancer before and after surgery and to determine their need
      for psychological care. METHODS: A group of 165 patients with lung cancer
      scheduled for surgical treatment were included in this study. They were asked to
      complete the Profile of Mood States questionnaire before surgery and on discharge
      after completion of treatment. The data on mood from the questionnaires were
      analyzed. RESULTS: Tension-anxiety improved significantly after surgery, whereas
      the fatigue score increased significantly. The scores for depression-dejection
      and confusion were elevated before surgery and were unchanged afterward.
      CONCLUSIONS: Patients with lung cancer were depressed before surgery and remained
      depressed after their operations, although postoperative tension-anxiety
      diminished. These results indicate that lung cancer patients need psychological
      support to alleviate depression during the perioperative period.

PMID- 17447511
TI  - Paraesophageal mediastinal desmoid tumor: case report.
AB  - A 45-year-old man presented with dysphagia. Computed tomography and magnetic
      resonance imaging showed an abnormal shadow in the paraesophageal mediastinum,
      which a thoracoscopic biopsy revealed to be a desmoid tumor that had infiltrated
      the surrounding tissues. We attempted esophageal stent placement; however, the
      esophageal stenosis could not be dilated, and bypass surgery was performed first,
      with tumor resection postponed, and radiation and hormonal therapy were added.
      Mediastinum desmoid tumors are rare, with only 22 other cases reported in the
      English language literature. Herein, we report the details of our patient and
      provide a review of other cases.

PMID- 17447512
TI  - Successful thoracoscopic treatment of severe bilateral empyema in an infant.
AB  - We report a case of rapid progression of bilateral pyothorax exacerbated by viral
      influenza in an infant. The patient, an 11-month-old girl, was diagnosed with
      viral influenza, and oseltamivir phosphate was administered. However, after only
      4 days the influenza was followed by rapid progression of methicillin-susceptible
      Staphylococcus aureus (MSSA) pneumonia and pyothorax, resulting in disseminated
      intravascular coagulation. Because thoracentesis and antibiotics could not
      control the pyothorax, a serious condition, we performed bilateral video-assisted
      thoracoscopic decortication on the eighth hospital day. She recovered with
      excellent lung expansion and was discharged on the 37th hospital day.

PMID- 17447513
TI  - Cavernous hemangioma of the rib diagnosed preoperatively by percutaneous needle
      biopsy.
AB  - A 74-year-old man presented to our hospital with persistent low-grade back pain
      that had continued for 6 months. An expansile tumor containing delicate bony
      trabeculae was found in the posterior portion of the left fifth rib. Preoperative
      examination of a percutaneous needle biopsy specimen suggested a diagnosis of
      hemangioma; postoperative pathology examination of the resected tumor confirmed
      this diagnosis. We emphasize the value of preoperative needle biopsy in
      determining the most suitable treatment for these rib tumors.

PMID- 17447514
TI  - Broncholithiasis managed by surgical resection.
AB  - Broncholithiasis is frequently associated with hemoptysis and infection. The most
      common cause of the disease is the presence of calcified material in a bronchus
      or in a cavity communicating with a bronchus. We present two cases of
      broncholithiasis treated by surgery. Case 1 involves a 57-year-old woman who
      presented with cough and bloody sputum. She had suffered from recurrent pneumonia
      in the left lower lobe caused by broncholithiasis for 2 years. We performed left
      S6 segmentectomy with bronchoplasty after unsuccessful bronchoscopic removal.
      Case 2 is a 65-year-old man who had had hilar tuberculous lymphoadenopathy at the
      age of 20. Recently he had suffered from recurrent bloody sputum and pulmonary
      suppuration for 3 years. We performed right upper lobectomy because the right B3
      was occluded by inflammatory granulation with calcification. Postoperatively,
      these two patients have been alive and well with no complications. The
      indications of surgery for broncholithiasis include a difficult bronchoscopic
      broncholithectomy, massive hemoptysis, and irreversible complications such as
      chronic pulmonary suppurative disease.

PMID- 17447515
TI  - Pulmonary mucinous cystadenocarcinoma: an extremely rare tumor presenting as a
      cystic lesion of the lung.
AB  - Pulmonary mucinous cystadenocarcinoma (PMC) is a rare tumor characterized by
      mucin production. It is similar to tumors of the same name arising in the ovaries
      and pancreas. Here we describe the 20th case of PMC reported in the English
      literature. The patient was a 75-year-old woman with a 3-day history of bloody
      sputum. Chest radiography and computed tomography revealed a cavitary mass 5 cm
      in diameter in the posterior segment of the right lung. 18F-fluorodeoxyglucose
      positron emission tomography demonstrated intense uptake in the wall of the
      lesion. Right lower lobectomy was performed, and the pathology examination
      revealed this tumor to be a PMC. The preoperative serum CA 19-9 level was 162.3
      U/ml (cutoff 37 U/ml) and decreased to 22.8 U/ml after resection. No mutation of
      epidermal growth factor receptor or K-ras gene was detected. Thoracic surgeons
      should bear in mind this rare tumor for the differential diagnosis of a pulmonary
      cystic lesion.

PMID- 17447516
TI  - [Less invasive treatment of intractable epilepsy--vagus nerve stimulation and
      stereotactic radiosurgery].
AB  - Vagus nerve stimulation (VNS) and stereotactic radiosurgery (SRS) represent novel
      and less invasive therapeutics for medically intractable epilepsy. VNS ushered in
      the recent advancement in clinical application of electrical stimulation therapy
      for epilepsy. Chronic stimulation of the left vagus nerve with implanted
      generator and electrodes inhibits seizure susceptibility of the cerebral
      cortices. Its efficacy and safety have been established by randomized clinical
      trials in 1990s in the Western countries and it has been widely accepted as a
      treatment option for patients with medically intractable epilepsy for whom brain
      surgery is not indicated or failed. Although the effect on seizures is not so
      dramatic, the less invasiveness and a wide range of indication have made VNS
      indispensable for comprehensive care of epilepsy. Since the devices are not
      approved for clinical use in Japan, there exist barriers to provide VNS to
      patients at present. Use of SRS for intractable epilepsy started in mid 90s as
      gamma knife surgery for mesial temporal lobe epilepsy. The marginal dose of 25 Gy
      to the medial temporal structures has been confirmed to be effective for seizure
      control, but there seems to be an unignorable risk of brain edema and radiation
      necrosis. It is still controversial whether the therapy is more effective and
      less invasive than brain surgery. A randomized clinical trial using the dose of
      20 or 24 Gy is ongoing in the United States. SRS for intractable epilepsy
      associated with hypothalamic hamartoma has been advocated because of a high
      surgical morbidity, but further study is needed for standardization of the
      treatment. Substitute use of SRS for other surgical technique like callosotomy or
      disconnection of epileptic focus seems to be another direction worth pursuing.

PMID- 17447517
TI  - [Electroconvulsive therapy for neurological disorders].
AB  - Electroconvulsive therapy (ECT) recovers the brain function through generalized
      convulsion induced by electrical stimulation of the brain. While the primary
      targets of ECT are psychiatric disorders such as depression, schizophrenia, and
      schizoaffective disorder, it has been well documented that ECT has therapeutic
      effects on muscular rigidity of Parkinson's disease and neuroleptics-induced
      malignant syndrome. Recently we demonstrated that ECT reduces intractable pain
      and allodynia associated with deafferentation pain disorders by recovering the
      function of the thalamic nucleus. ECT, if applied on appropriate clinical
      assessments, may contribute to the therapeutics of neuropsychiatric disorders.

PMID- 17447518
TI  - [Restoration of hearing--comparing auditory brainstem implant to cochlear
      implant].
AB  - Restorative neurosurgery proceeds in the two ways, through biological means or
      through nerve-computer interface technology. Stem cells are now expected to
      repair the injured spinal cord and cochlear implants have already restored
      hearing in many patients. These examples represent each of these methodologies,
      respectively. The auditory brainstem implant is an extension of the technology of
      the cochlear implant. In this review article, the author summarizes the present
      status of auditory brainstem implant (ABI), comparing it to cochlear implant
      (CI). CI restores hearing by stimulating the cochlear nerve in the cochlea for
      patients whose deafness has been caused by inner ear disease; ABI does it by
      stimulating the cochlear nucleus of the brainstem for those deaf due to bilateral
      cochlear nerve dysfunction. In the world, up until now, more than 700 patients,
      almost all of whom are neurofibromatosis type 2, have undergone ABI and had
      hearing restored. Hearing performance by ABI, however, is not so good as that by
      CI. To improve the quality of hearing by ABI, new techniques such as advanced
      coding strategies and depth electrodes are now being introduced.

PMID- 17447519
TI  - [Vision engineering--photoelectric dye-based retinal prostheses: Okayama
      University model].
AB  - Patients with retinitis pigmentosa lose photoreceptor cells by genetic
      abnormalities and hence become blind. Neurons such as bipolar cells and ganglion
      cells still remain alive even in the retina of these patients, and ganglion cells
      send axons to the brain as the optic nerve. The replacement of dead photoreceptor
      cells with something artificial is the basic concept of retinal prostheses. The
      remaining retinal neurons can be stimulated by either electric current or
      electric potential. Photodiode array and electrode array are two main ways to
      stimulate retinal neurons as retinal prostheses. These retinal prostheses have
      problems such as low sensitivity and requiring outer electric sources
      (batteries). To overcome the problems, we are developing photoelectric dye-based
      retinal prostheses which absorb light and convert photon energy to electric
      potentials. The prototype, photoelectric dye-coupled polyethylene film, could
      generate intracellular calcium elevation in photoreceptor-lacking retinal tissues
      and also in cultured retinal neurons. The photoelectric dye-based retinal
      prostheses are thin and soft, and therefore, a sheet of the film in a large size,
      corresponding to wide visual field, can be inserted into the vitreous and then to
      the subretinal space through a small opening by rolling up the film. After the
      production control and the quality control have been established, clinical trials
      of the photoelectric dye-based retinal prostheses would be planned in concordance
      with the Drugs and Medical Devices Law to prove the safety and the efficacy.

PMID- 17447520
TI  - [Hematopoietic cell transplantation in X-linked adrenoleukodystrophy].
AB  - X-linked adrenoluekodystrophy (X-ALD) is a clinically heterogenous disorder
      ranging from the rapidly progressive childhood cerebral form to the milder
      adrenomyeloneuropathy in adults, and some persons with ALD protein (ALDP) defects
      may remain asymptomatic for life. Hematopoietic cell transplantation (HCT) is
      currently the only effective therapy for cerebral X-ALD. Stem cell sources for
      transplantation are bone marrow, peripheral blood and cord blood. The donor
      should be HLA identical with the recipient and can be found within family members
      or from unrelated bone marrow or cord blood donor pools. Preparative conditioning
      with supralethal chemoradiotherapy is needed for donor cell engraftment, and
      immunosuppressive agents are given for months as prophylaxis against graft-verus
      host disease (GVHD). Worldwide data collection reported 56% of long term
      survival. Neurologic and MRI severity at the time of transplantation was the most
      important factor for survival and the degree of improvement after
      transplantation. More than 90% of early stage patients have survived with good
      quality of life for a long term, whereas patients with advanced disease had the
      higher mortality rate during transplant procedures and the neurological
      abnormalities progressed in most of them. Patients with a parietal-occipital lobe
      pattern of demyelination demonstrated a greater mean loss of performance IQ (PIQ)
      points than patients with a frontal lobe pattern of demyelination. Thus, boys
      with early-stage disease benefit from HCT, whereas boys with advanced disease may
      be candidates for experimental therapies.

PMID- 17447521
TI  - [Neuroscience based strategies for neurorehabilitation].
AB  - Recent advances in basic neuroscience revealed that functional recovery after
      brain damages is attributed to vicarious function of neural networks. From
      clinical point of view, functional neuroimaging and neurophysiological testing
      also have shown functional reorganization of the damaged neural networks after
      stroke. Understanding of such neural mechanisms has induced an evolutional
      progress in strategies for neurorehabilitation. Use-dependent plasticity of the
      central nervous system is attributed to both dose-dependent and context dependent
      effects of rehabilitative intervention referred as enriched environment and
      enriched rehabilitation. For instance constraint-induced movement therapy
      emphasizes not only forced use of the paretic hand but also "shaping" by which
      patients are always rewarded in structural and progressive approaches. Principals
      of motor learning such as task-oriented repetitive and rhythmical approaches,
      feedback of knowledge of results and mental practice using motor imagery has been
      also applied to rehabilitative strategies. Robot-assisted rehabilitation also
      provides useful information about the context of neurorehabilitation. There is
      accumulative evidence that plasticity of the damaged brain is modified by
      neuropharmacological intervention and noninvasive and invasive brain stimulation
      coupled with rehabilitation. Furthermore development of brain-machine interfaces
      might enable to produce new connections among brain regions, muscles, computer
      and prosthesis bypassing the damaged area. Efficacy of these strategies is based
      on the assumption that the damaged areas are stable. However if these strategies
      results in dramatic enhancement and acceleration of functional recovery, patients
      with neurological diseases of recurrent or degenerative nature might also have
      real-world benefit, which is trade-off between gains and progression, from
      neurorehabilitation.

PMID- 17447522
TI  - [Cognitive rehabilitation--the learning therapy for the senile dementia].
AB  - The conventional cognitive rehabilitation was the technique for the patients with
      the neuropsychological disorders such as aphasia, apraxia, agnosia, attentional
      disorder, memory impairment, and executive function disorder. These disorders
      were induced by the organic brain damages due to the traumatic brain injury or
      the stroke. The aim of the conventional cognitive rehabilitation was to recover
      their impaired function and improve their quality of life. Recently, subjects of
      cognitive rehabilitation were not only the patients with the organic brain
      damages but also the patients with the functional brain impairment including a
      dementia. Kawashima et al. developed "The learning therapy" as a cognitive
      rehabilitation for the senile dementia through the top-down approach, the concept
      of which was derived from the knowledge of the functional brain imaging. The
      learning therapy is defined as a training of simple arithmetic calculation and
      reading aloud communicating with a trainer. The effect of The learning therapy is
      to keep and improve the prefrontal function including cognitive function, ability
      of communication and independence. It was confirmed that The learning therapy was
      an effective cognitive rehabilitation for the senile dementia patients by
      improving their prefrontal function. The effect of prevention against dementia is
      also being studied. Furthermore, we propose a new educational program for the
      cognitive development disorders to improve their prefrontal functions.

PMID- 17447523
TI  - [Paradigm shift in clinical trials for neurodegenerative diseases].
AB  - Neurodegenerative diseases have been construed as incurable disorders. However,
      therapeutic development for these diseases is now facing a turning point:
      analyses of cellular and animal models have provided insights into pathogenesis
      of neurodegenerative diseases, and have indicated rational therapeutic approaches
      to them. Therefore, how to design clinical trials for neurodegenerative diseases
      is becoming one of the most challenging issues in the clinical neurology. Given a
      small number of patients and a slow progression of symptoms, it is important to
      carry out effective trials using surrogate endpoints or historical control data,
      if necessary. In particular, pathogenesis-based disease-modifying therapy should
      be carefully evaluated in clinical trials, because its effect is likely to be
      suppression of neurodegenerative processes, but not symptom relief. The
      development of androgen deprivation therapy for spinal and bulbar muscular
      atrophy (SBMA) is a representative study in this field. SBMA is a hereditary
      neurodegenerative disease caused by expansion of a trinucleotide CAG repeat,
      which encodes the polyglutamine tract, in the first exon of the androgen receptor
      (AR) gene. Animal models carrying human mutant AR gene recapitulate polyglutamine
      mediated motor neuron degeneration, providing insights into the pathogenesis of
      SBMA. There is increasing evidence that testosterone, the ligand of AR, plays a
      pivotal role in the neurodegeneration in SBMA. The striking success of androgen
      deprivation therapy in SBMA mouse models has been translated into phase 2, and
      then phase 3, clinical trials.

PMID- 17447524
TI  - [Vaccination therapy for Alzheimer's disease].
AB  - Alzheimer's disease is a neurodegenerative disorder characterized by senile
      plaques in the brain. In the senile plaques beta-amyloid is deposited and
      neuroinflammation due to innate immune responses against beta-amyloid is thought
      to cause degeneration of synapses and neural processes. In 1999 Dale Schenk et
      al. discovered that immunization of amyloid precursor protein (APP) transgenic
      mice with amyloid-beta protein (A-beta) reduces senile plaques and prevents new
      deposits of beta-amyloid. They also have found that antibodies to A-beta have
      similar effect. Since immunized mice showed improvement of cognitive functions,
      an active immunization method was tested in humans. However, the trial was halted
      because of side effect, subacute meningoencephalitis due to T-cell mediated
      autoimmune responses. We developed a safe oral A-beta vaccine using adeno
      associated virus vector. When this vaccine was given once, antibodies were
      elevated well and high titers were kept for over 6 months. APP transgenic mice
      and old monkeys showed significant reduction of amyloid burden without any side
      effect. Since Th1 immune responses are suppressed in the gut immune system, this
      is a promising way to treat and prevent Alzheimer's disease.

PMID- 17447525
TI  - [A strategy to develop effective ALS therapy].
AB  - In the early 1990s, a number of major events took place in the history of the
      treatment and science of ALS. A cause of familial ALS, the mutation of superoxide
      dismutase 1, was discovered and very shortly after, an animal model expressing
      the human SOD1 mutation for familial ALS was generated. Around the same time, the
      first medication for the treatment of ALS, riluzole, was approved. Clinical
      neurologists started to focus more attention on quality of life and standardizing
      care for patients with ALS, including devising approaches for presenting and
      discussing the diagnosis, using aggressive symptomatic treatments, and developing
      a multidisciplinary care system. Since then, nutritional and respiratory care has
      markedly improved. Respiratory care for those with terminal ALS in Japan has been
      distinct and perhaps more effective compared to the rest of the world, and this
      unique experience must be broadly published and shared with others. In 1999, the
      ALS Treatment Guidelines were published by the American Academy of Neurology and
      are now under revision. A monitoring system to determine the impact the
      Guidelines had on actual patient care has taught us that caregivers have only
      slowly accepted the recommendation to improve quality of care. The team approach,
      using a multidisciplinary care system from diagnosis to the end of life, is
      essential to improve care for both the patient and family. Coinciding with the
      progress in ALS treatment, basic science and translational research also produced
      dramatic progress in ALS drug discovery. Over the past 15 years, more than 25
      potential drugs have been tested in randomized controlled trials. Despite this
      progress, we have no medications other than riluzole. Although it may be true
      that ALS research is in its early stages compared to research in other diseases
      with no cure--it is probably behind cancer research by at least 20 or 30 years-
      we need to drastically change our approach to drug development. At a national
      level, we need to create a strong, cohesive team with support from a number of
      funding agencies, oversight from a regulatory agency, and investigators who all
      think "outside the box." In addition, we should obtain ideas and suggestions from
      accomplished experts outside of the field of ALS and put competition aside as we
      work together to develop strategic plans for the ALS drug development that is
      essential to beat this devastating disease.

PMID- 17447526
TI  - [Therapeutic strategies for the polyglutamine diseases].
AB  - The polyglutamine diseases are a group of nine inherited neurodegenerative
      diseases including Huntington disease, spinocerebellar ataxia type 1, 2, 3, 6, 7
      and 17, dentatorubral pallidoluysian atrophy, and spinobulbar muscular atrophy,
      which are caused by an abnormal expansion of the CAG repeat encoding a
      polyglutamine stretch in each unrelated disease-causing gene. In the pathogenesis
      of the polyglutamine diseases, expansion of the polyglutamine stretch causes
      misfolding and conformational alterations of the disease-causing proteins,
      leading to pathogenic protein-protein interactions including aggregate formation,
      and subsequently resulting in their deposition as inclusion bodies in affected
      neurons. Expression of these expanded polyglutamine proteins has been reported to
      impair protein degradation, transcriptional regulation, axonal transport,
      mitochondrial function, etc., which eventually result in neurodegeneration.
      Currently, a wide variety of research towards establishing therapies targeting
      each step in the pathogenesis of the polyglutamine diseases is in progress, which
      includes suppressing mutant gene expression by RNAi, inhibiting protein
      misfolding/aggregation, promoting protein degradation, activating transcription,
      activating mitochondrial function, inhibiting neuronal cell death, and
      neuroprotection by neurotrophic factors. Standardized validation of these
      preclinical studies and development of sensitive biomarkers for evaluation of
      therapeutic efficacy in clinical trials will be necessary for development of
      drugs for the polyglutamine diseases.

PMID- 17447527
TI  - [Development of molecular target based-therapy for prion diseases].
AB  - Prion diseases, or transmissible spongiform encephalopathies, are fatal,
      neurodegenerative diseases that include Creutzfeldt-Jacob disease (CJD) in
      humans, bovine spongiform encephalopathy (BSE) and scrapie in animals. Prion
      diseases are characterized by the accumulation of a misfolded prion protein,
      PrPSc, which is made by a posttranslational conformational change of the host
      encoded cellular prion protein, PrPC. The process of the conformational change
      remains enigmatic, but a large number of researches on the therapeutic
      intervention have been done in experimental models over the past 30 years.
      Against the background of the occurrence of variant CJD in the UK in the 1990s,
      which is considered to occur by transmission of the BSE agent and to possibly
      spread through secondary infection via blood transfusion, the research on the
      development of therapeutic agents has been accelerated using an increasing number
      of disease models in animals, cells and in vitro system. Candidate therapeutic
      targets for prion diseases include the following four factors: the PrPC; the
      PrPSc; the cellular factors associated with the conversion of PrPC into PrPSc;
      the cellular factors responsible for the neurodegenerative processes. In this
      article, recent advances in the therapeutic development for prion diseases on the
      basis of molecular targeting are reviewed, and its future perspectives are
      discussed.

PMID- 17447528
TI  - [Therapeutic strategy for muscular dystrophies].
AB  - A successful cure for muscular dystrophies has yet to be demonstrated, but we
      could notice spectacular progress for the past few years. Advances have been made
      in methods of delivering foreign genes into muscle cells, either as naked plasmid
      DNA or via viral vectors. Among the virus-based methods, results with adeno
      associated viral vectors have been the most promising. Systemic administration of
      anti-sense oligonucleotides has shown incredible success in inducing dystrophin
      expression and ameliorating muscle pathology via exon skipping in canine models
      of muscular dystrophy. Biochemical and functional rescue of dystrophic muscle has
      also been demonstrated with the transplantation of normal or genetically modified
      myogenic stem cells, as well as with a number of pharmacological approaches in
      animal models. Here we review the current researches on the treatment of muscular
      dystrophies and clinical trials on Duchenne muscular dystrophy.

PMID- 17447529
TI  - [Gene therapy for Parkinson's disease].
AB  - Recombinant adeno-associated viral (rAAV) vectors are safer and more effective
      than other in vivo gene delivery methods. Stereotaxic injection of the vectors
      provides continuous and selective expression of therapeutic proteins throughout
      the target area in primate brains without toxicity. Three phase I clinical trials
      for gene therapy for Parkinson's disease (PD) using rAAV vectors are currently
      underway. One trial involves gene transfer of aromatic L-amino acid decarboxylase
      (AADC), an enzyme that converts L-dopa to dopamine, to restore therapeutic
      windows of orally administered L-dopa in advanced idiopathic PD. After AADC
      transduction, the daily required dose of L-dopa can be reduced and the duration
      of the ON period is prolonged. Another trial involves transduction of the
      subthalamic nucleus (STN) with rAAV vectors expressing glutamic acid
      decarboxylases, a rate-limiting enzyme for synthesizing inhibitory the
      neurotransmitter gamma-aminobutyric acid (GABA). This strategy, which is similar
      to deep brain stimulation, aims at modulating hyperactive STN neurons, thereby
      alter the resulting activity of down-stream targets, which influence movement.
      However, the mechanism of stimulation remains unknown, and there are some
      theoretical concerns of chemical alteration. The other trial involves delivery of
      rAAV vectors expressing neurturin, a natural analog of a glial cell line-derived
      neurotrophic factor, into the putamen to slow down the ongoing degeneration of
      nigral dopaminergic neurons. Positron emission tomography with various tracers
      has been used to monitor the effects of therapeutic gene expression in vivo.
      Although no serious adverse effects of gene transfer have been reported so far in
      these trials, vector systems that regulate transgene expression are necessary to
      increase safety, and the development of such systems is in progress. Gene therapy
      using rAAV vectors may be a promising option for treatment of PD in the near
      future.

PMID- 17447530
TI  - [Rehabilitation for myositis in acute phase].
AB  - Polymyositis and dermatomyositis (PM/DM) are representative inflammatory muscle
      diseases. In treatment of PM/DM, drug therapies are cardinal but rehabilitation
      may be another option. Since muscles with PM/DM are fragile for muscle exercise,
      rehabilitation has been recommended mainly in chronic phase. Some researchers
      considered that rehabilitation for PM/DM patients in acute phase may improve
      their functional prognosis without major sideeffect. However, there are
      controversies about rehabilitation for PM/DM patients from acute phase. To
      consider advisability, I reviewed literatures concerning rehabilitation for PM/DM
      patients in acute phase.

PMID- 17447531
TI  - [A case of neuralgic amyotrophy in the lower extremity (lumbosacral
      radiculoplexus neuropathy)].
AB  - We report a 76-year-old man who suddenly had pain in the right buttock that
      radiated down the back of the leg. He underwent nerve block therapy, but
      subsequently noted weakness of the right leg. On examination, there was moderate
      weakness of the right gastrocnemius, flexor digitorum longus and extensor hallcis
      longus, and mild weakness of the tibialis anterior, quadriceps and hamstrings
      muscles. The right Achilles tendon reflex was absent. There was a slight
      diminution of touch sensation over the right L5-S1 area. A nerve conduction study
      revealed reduced motor and sensory action potentials in the right leg. An
      electromyography showed evidence of denervation in the right gastrocnemius and
      tibialis anterior muscles. Treatment with corticosteroids was effective for
      alleviating his pain, and muscle strength improved gradually. One year later, he
      showed no neurological deficits. Neuralgic amyotrophy in the lower extremities is
      rare, but awareness of this disorder helps us avoid unnecessary surgical
      investigations and leads to possible treatment with immunomodulative therapy.

PMID- 17447532
TI  - [Charles Bell "The nervous system of the human body" 1830].

PMID- 17447533
TI  - Interview with Vivian Echavarria, FACHE, Director of Operations, Alaska Native
      Medical Center. Interview by Kyle L Grazier.

PMID- 17447534
TI  - The new frontier of electronic, personal, and virtual health records.

PMID- 17447535
TI  - Diversity management and cultural competence: research, practice, and the
      business case.

PMID- 17447536
TI  - Healthcare executives' role in preparing for the pandemic influenza 'gap': a new
      paradigm for disaster planning?

PMID- 17447537
TI  - The early experience of a hospital-based pay-for-performance program.
AB  - This study evaluated the effect of a health-plan-sponsored, hospital-based
      financial incentive program, focused on heart-failure quality indicators, to
      improve quality. We conducted separate, hour-long, semistructured group
      interviews with senior managers and cardiologists at ten hospitals involved in
      the Participating Hospital Agreement (PHA) program implemented by Blue Cross Blue
      Shield of Michigan (BCBSM). Under PHA, hospitals are eligible for an annual
      incentive payment of up to 4 percent of BCBSM's diagnosis-related-group-based
      inpatient claims, depending on their performance in patient safety, community
      outreach, and selected quality indicators. Interviews focused on knowledge,
      perceptions, and impact of pay-for-performance (P4P) strategies. We compared
      BCBSM-provided data on heart-failure quality indicators between 2002 and 2004
      with our qualitative findings. Our analyses suggest that pursuit of incentive
      based quality targets may be largely dependent on the context of a particular
      hospital. In settings where performance did not change, incentives did not appear
      to drive organizational or individual practice changes. Underperforming hospitals
      with some of the infrastructure necessary for quality improvement had the
      greatest success when presented with incentives. We concluded that one formula
      for a successful P4P program is to direct incentive payment to an organized
      entity capable of supporting process improvement by applying resources and
      organizational expertise. In this model, the incentive program supports the
      organization, and the organization in turn may apply resources to facilitate
      improvement in clinician performance. Consideration of the requirements of
      organizations to facilitate improvement in relation to existing quality
      improvement infrastructure may lead to the future success of hospital-based P4P
      programs.

PMID- 17447538
TI  - Links among high-performance work environment, service quality, and customer
      satisfaction: an extension to the healthcare sector.
AB  - Healthcare managers must deliver high-quality patient services that generate
      highly satisfied and loyal customers. In this article, we examine how a high
      involvement approach to the work environment of healthcare employees may lead to
      exceptional service quality, satisfied patients, and ultimately to loyal
      customers. Specifically, we investigate the chain of events through which high
      performance work systems (HPWS) and customer orientation influence employee and
      customer perceptions of service quality and patient satisfaction in a national
      sample of 113 Veterans Health Administration ambulatory care centers. We present
      a conceptual model for linking work environment to customer satisfaction and test
      this model using structural equations modeling. The results suggest that (1) HPWS
      is linked to employee perceptions of their ability to deliver high-quality
      customer service, both directly and through their perceptions of customer
      orientation; (2) employee perceptions of customer service are linked to customer
      perceptions of high-quality service; and (3) perceived service quality is linked
      with customer satisfaction. Theoretical and practical implications of our
      findings, including suggestions of how healthcare managers can implement changes
      to their work environments, are discussed.

PMID- 17447539
TI  - The relationship between weather and hospital emergency department volume.

PMID- 17447540
TI  - Structural and functional responses of river biofilm communities to the
      nonsteroidal anti-inflammatory diclofenac.
AB  - Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that has been
      detected widely in surface waters in North America and Europe. The impact of
      diclofenac on river biofilm communities was investigated at exposures of 10 and
      100 microg L(-1) of diclofenac or its molar equivalent in carbon and nutrients.
      Experiments were carried out with river water during spring and summer using
      rotating annular reactors as model systems. Diclofenac or nutrients at 10 microg
      L(-1) were observed to have no significant effect on algal, bacterial, and
      cyanobacterial biomass in spring, whereas in the summer the nutrient equivalent
      reduced algal biomass and diclofenac reduced cyanobacterial biomass relative to
      control biofilms (p < 0.05). In contrast, at 100 microg L(-1) diclofenac or
      nutrients, the result was increased cyanobacterial and bacterial biomass,
      respectively, relative to control biofilms in spring. In summer, 100 microg L(-1)
      diclofenac significantly increased bacterial biomass and the nutrient treatment
      had no significant effect (p < 0.05); both treatments resulted in increased
      biofilm thickness. The glycoconjugate composition of the exopolysaccharide matrix
      was influenced differentially by the treatments in both seasons. Biolog
      assessments of carbon use indicated that 100 microg L(-1) diclofenac or nutrients
      resulted in significant depressions in the use of carbon sources in summer and
      significant increases in spring. Impacts on protozoan and micrometazoan
      populations also were assessed. Denaturing gradient gel electrophoresis analyses
      of community DNA and fluorescent in situ hybridization studies indicated that
      diclofenac had significant effects on the nature of the bacterial community in
      comparison with control and nutrient-treated river biofilm communities.

PMID- 17447541
TI  - Soil factors controlling the toxicity of copper and zinc to microbial processes
      in Australian soils.
AB  - Abstract-Two soil microbial processes, substrate-induced nitrification (SIN) and
      substrate-induced respiration (SIR), were measured in the topsoils of 12
      Australian field trials that were amended separately with increasing
      concentrations of ZnSO4 or CuSO4. The median effect concentration (EC50) values
      for Zn and Cu based on total metal concentrations varied between 107 and 8,298 mg
      kg(-1) for Zn and 108 and 2,155 mg kg(-1) Cu among soils. The differences in both
      Zn and Cu toxicity across the 12 soils were not explained by either the soil
      solution metal concentrations or CaCl2-extractable metal concentrations, because
      the variation in the EC50 values was larger than those using total
      concentrations. Toxicity of Zn and Cu decreased with increasing soil pH for SIN.
      For Cu, also increasing cation exchange capacity (CEC) and percent clay decreased
      the toxicity towards SIN. In contrast to SIN, soil pH had no significant effect
      on toxicity values of SIR. Significant relationships were found between the EC50
      values for SIR and background Zn and CEC for Zn, and percent clay and log CEC for
      Cu. Relationships such as those developed in this study will permit Australian
      environmental regulation to move from single-value national soil quality
      guidelines to soil-specific quality guidelines and permit soil-specific risk
      assessments to be undertaken.

PMID- 17447542
TI  - Accumulation of polycyclic aromatic hydrocarbons in rural soils based on mass
      balances at the catchment scale.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are hydrophobic organic pollutants that
      are ubiquitously distributed in the environment at relatively high
      concentrations. In our study we investigated the long-term fate of atmospheric
      PAHs in soils of rural areas, resulting from diffuse pollution based on mass
      balances at the catchment scale. By determining PAHs in several environmental
      compartments, estimates of soil storages and water fluxes were made and compared
      with atmospheric deposition. The results indicate that more than 90% of the
      incoming PAHs remain in the catchments and accumulate in the topsoils.
      Furthermore, revolatilization of PAHs from soils and degradation in the soils is
      very limited, resulting in ongoing accumulation in topsoils, in particular for
      low-volatile PAHs. Combustion-derived carbonaceous particles were detected in
      atmospheric deposition as well as in the soil samples. Since these particles are
      very strong adsorbents, they are suspected to play a key role in the
      environmental fate of the diffuse distributed PAHs.

PMID- 17447543
TI  - A novel method using cyanobacteria for ecotoxicity test of veterinary
      antimicrobial agents.
AB  - The effect of antimicrobial agents for veterinary use on the growth of
      cyanobacteria was investigated by measuring minimum inhibitory concentration,
      medium effective concentration (EC50), and no-observed-effect concentration of
      seven antimicrobial agents for eight cyanobacteria. The results demonstrated that
      the seven antimicrobial agents, even at low concentrations, inhibited the growth
      of cyanobacteria. Microcystis aeruginosa and Synechococcus sp. had the highest
      sensitivity to the antimicrobial agents used in the present study. It is
      considered that the utilization of cyanobacteria would enable easy and highly
      sensitive assessment of the toxicity of such chemicals as antimicrobial agents.
      We suggest that cyanobacteria be used for ecotoxicity test in addition to the
      hitherto established method that uses green algae.

PMID- 17447544
TI  - Impact of polychlorinated biphenyl and polycyclic aromatic hydrocarbon
      sequestration in sediment on bioaccumulation in aquatic food webs.
AB  - It is not clear whether sequestration or aging of organic chemicals like
      polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs)
      limits accumulation in higher levels of aquatic food chains. Therefore, the
      effect of aging on accumulation was studied in 1(-m3) model ecosystems that
      mimicked fish-dominated, macrophyte-dominated, and fish- and macrophyte-dominated
      shallow lakes. Also treatments without fish and macrophytes were included.
      General characteristics, biomasses, total (Soxhlet-extractable), and labile (6-h
      Tenax-extractable) PCB and PAH concentrations in sediment and biota were
      monitored over time. Accumulation data for PCB 28, PCB 149, and fluoranthene
      (native to the sediment taken from the field) were compared to those for spiked
      analogues PCB 29, PCB 155, and fluoranthene-d10. Labile fractions for spiked
      compounds were higher than for their native analogues and decreased over time,
      suggesting sequestration in the sediment. In the majority of cases, 6-h Tenax
      extractable concentrations correlated better with concentrations in biota than
      Soxhlet-extractable concentrations. Ecosystem structure affected food web
      accumulation, but replicate variability was too high to detect clear treatment
      effects. Differences in accumulation between spiked compounds and their native
      analogues indicated an effect of aging for invertebrates, macrophytes, and
      benthivorous fish. Thus, aging may translate directly into reduced uptake at
      higher trophic levels.

PMID- 17447545
TI  - Polybrominated diphenyl ethers in biota and sediments of the Pearl River Estuary,
      South China.
AB  - Polybrominated diphenyl ethers (PBDEs) were analyzed in three invertebrate
      species, five fish species with different living and feeding habits, and surface
      sediments collected from the Pearl River Estuary, South China. The concentrations
      of 10 PBDE congeners (BDEs 28, 47, 66, 99, 100, 85, 154, 153, 138, and 183)
      ranged from 34.1 to 444.5 ng/g lipid and from 9.88 to 39.0 ng/g organic carbon in
      biota and sediment samples, respectively. In sediments and some biota samples,
      BDE 209 was found as the major congener, ranging from nondetectable to 623.5 ng/g
      lipid in biota samples and from 792 to 4,137 ng/g organic carbon in sediment
      samples. Different levels of PBDEs in various biota species were attributed to
      the different feeding habits of the aquatic species or their ability to
      metabolize PBDE. Different congener profiles between the biota and sediment
      samples were observed and attributed to the bioaccumulation potential or the
      ability to metabolize individual BDE congeners. Polybrominated diphenyl ether
      levels in the biota from the Pearl River Estuary correlated well with lipid
      contents but did not correlate with the biota lengths. The distribution of biota
      sediment accumulation factors for individual PBDE congeners was consistent with
      the general pattern predicted from a widely used bioaccumulation model.

PMID- 17447546
TI  - Influence of dissolved organic matter on the complexation of mercury under
      sulfidic conditions.
AB  - The complexation of Hg under sulfidic conditions influences its bioavailability
      for microbial methylation. Neutral dissolved Hg-sulfide complexes are readily
      available to Hg-methylating bacteria in culture, and thermodynamic models predict
      that inorganic Hg-sulfide complexes dominate dissolved Hg speciation under
      natural sulfidic conditions. However, these models have not been validated in the
      field. To examine the complexation of Hg in natural sulfidic waters,
      octanol/water partitioning methods were modified for use under environmentally
      relevant conditions, and a centrifuge ultrafiltration technique was developed.
      These techniques demonstrated much lower concentrations of dissolved Hg-sulfide
      complexes than predicted. Furthermore, the study revealed an interaction between
      Hg, dissolved organic matter (DOM), and sulfide that is not captured by current
      thermodynamic models. Whereas Hg forms strong complexes with DOM under oxic
      conditions, these complexes had not been expected to form in the presence of
      sulfide because of the stronger affinity of Hg for sulfide relative to its
      affinity for DOM. The observed interaction between Hg and DOM in the presence of
      sulfide likely involves the formation of a DOM-Hg-sulfide complex or results from
      the hydrophobic partitioning of neutral Hg-sulfide complexes into the higher
      molecular-weight DOM. An understanding of the mechanism of this interaction and
      determination of complexation coefficients for the Hg-sulfide-DOM complex are
      needed to adequately assess how our new finding affects Hg bioavailability,
      sorption, and flux.

PMID- 17447547
TI  - Hazard characterization and identification of a former ammunition site using
      microarrays, bioassays, and chemical analysis.
AB  - More than 100,000 tons of 2,4,6-trinitrotoluene were produced at the former
      ammunition site Werk Tanne in Clausthal-Zellerfeld, Germany. The production of
      explosives and consequent detonation in approximately 1944 by the Allies caused
      great pollution in this area. Four soil samples and three water samples were
      taken from this site and characterized by applying chemical-analytical methods
      and several bioassays. Ecotoxicological test systems, such as the algal growth
      inhibition assay with Desmodesmus subspicatus, and genotoxicity tests, such as
      the umu and NM2009 tests, were performed. Also applied were the Ames test,
      according to International Organization for Standardization 16240, and an Ames
      fluctuation test. The toxic mode of action was examined using bacterial gene
      profiling assays with a battery of Escherichia coli strains and with the human
      liver cell line hepG2 using the PIQOR Toxicology cDNA microarray. Additionally,
      the molecular mechanism of 2,4,6-trinitrotoluene in hepG2 cells was analyzed. The
      present assessment indicates a danger of pollutant leaching for the soil
      groundwater path. A possible impact for human health is discussed, because the
      groundwater in this area serves as drinking water.

PMID- 17447548
TI  - Analysis of organotins in seawater of the Southern Ocean and Suruga Bay, Japan,
      by gas chromatography/inductively coupled plasma mass spectrometry.
AB  - Organotins are widespread in the world's oceans and have a detrimental effect on
      organisms. However, there is little information on their distribution in the
      Southern hemisphere. We analyzed organotins in seawater from the Southern Ocean
      and Suruga Bay, Japan, using gas chromatography/inductively coupled plasma mass
      spectrometry. Organotins were compared in two contrasting environments--one in
      shallow, temperate coastal waters (Suruga Bay) and the other in cold, deep waters
      of the far Southern Ocean. Twelve kinds of organotins were detected from Suruga
      Bay, with tributyltin (0.184-13.6 ng Sn/L) and total organotins (0.801-19.7 ng
      Sn/L). In contrast, three kinds of organotins were detected in the Southern
      Ocean, with total organotins (from not detected to 0.266 ng Sn/L). The ratios of
      degraded products of tributyltin and triphenyltin from the Southern Ocean were
      higher than those in Suruga Bay, suggesting that fresh input of organotins into
      the Southern Ocean is relatively low. The presence of butyltins in Antarctic
      sediments and biota has been demonstrated previously; however, the present study
      is the first to describe trace levels of organotins in the Southern Ocean
      approximately 1,000 km from Antarctica.

PMID- 17447549
TI  - Biogeochemical factors affecting mercury methylation in sediments of the Venice
      Lagoon, Italy.
AB  - Mercury methylation and sulfate reduction rates, total Hg, and monomethyl Hg in
      the sediments of the Venice Lagoon (Italy) were measured in June 2005 in order to
      identify the factors affecting the methylation of inorganic Hg. While the rates
      of Hg methylation and sulfate reduction were generally higher in the surface
      layers (0-2.5 cm), the correlation between Hg methylation and sulfate reduction
      rates was not significant when considering all depths and sites. This discrepancy
      is discussed considering two factors: the activity of sulfate-reducing bacteria
      and Hg solubility. The former factor is important in determining the Hg
      methylation rate in comparable geochemical conditions as evidenced by similar
      vertical profiles of Hg methylation and sulfate reduction rates in each sediment
      core. The latter factor was assessed by comparing the Hg methylation rate with
      the particle-water partition coefficient of Hg. The Hg methylation rates
      normalized to sulfate reduction rates showed a negative linear correlation with
      the logarithm of the particle-water partition coefficient of Hg, suggesting that
      the availability of dissolved Hg is a critical factor affecting Hg methylation.
      Solid FeS seems to play an important role in controlling the solubility of Hg in
      Venice Lagoon sediments, where sulfate and iron reductions are the dominant
      electron-accepting processes. Overall, the production of monomethyl Hg in the
      Venice Lagoon is controlled by a fine balance between microbial and geochemical
      processes with key factors being the microbial sulfate reduction rate and the
      availability of dissolved Hg.

PMID- 17447550
TI  - Removal of cadmium ions during stationary growth phase by an extremely cadmium
      resistant strain of Stenotrophomonas sp.
AB  - Stenotrophomonas sp. CD02 was isolated from a site that previously had been
      contaminated with high concentrations of the heavy metals cadmium (3 mg kg(-1))
      and chromium (115 mg kg(-1)). This strain was able to grow on complex (Luria
      Bertani) medium containing high concentrations of cadmium ion (up to 4 mM).
      Additionally, it could remove up to 80% of the dissolved ions but only after
      reaching stationary growth phase. Strain CD02 also tolerated high concentrations
      of other heavy metals such as chromium, zinc, copper, nickel, and lead at levels
      more than 2 mM. Although strain CD02 can tolerate much higher cadmium
      concentrations than the three Stenotrophomonas maltophilia strains tested, they
      all possess resistance to the same range of antibiotics. This suggests that
      strain CD02 possesses a mechanism that allows it to tolerate and remove cadmium
      differently from those conferring resistance to antibiotics. Strain CD02 can be a
      suitable candidate for heavy metal bioremediation in contaminated environment
      because it is able to tolerate high concentration of heavy metals and remove
      cadmium aerobically.

PMID- 17447551
TI  - Development of a Daphnia magna DNA microarray for evaluating the toxicity of
      environmental chemicals.
AB  - Toxic chemical contaminants have a variety of detrimental effects on various
      species, and the impact of pollutants on ecosystems has become an urgent issue.
      However, the majority of studies regarding the effects of chemical contaminants
      have focused on vertebrates. Among aquatic organisms, Daphnia magna has been used
      extensively to evaluate organism- and population-level responses of invertebrates
      to pollutants in acute toxicity or reproductive toxicity tests. Although these
      types of tests can provide information concerning hazardous concentrations of
      chemicals, they provide no information about their mode of action. Recent
      advances in molecular genetic techniques have provided tools to better understand
      the responses of aquatic organisms to pollutants. In the present study, we
      adapted some of the techniques of molecular genetics to develop new tools, which
      form the basis for an ecotoxicogenomic assessment of D. magna. Based on a Daphnia
      expressed sequence tag database, we developed an oligonucleotide-based DNA
      microarray with high reproducibility. The DNA microarray was used to evaluate
      gene expression profiles of neonatal daphnids exposed to several different
      chemicals: Copper sulfate, hydrogen peroxide, pentachlorophenol, or beta
      naphthoflavone. Exposure to these chemicals resulted in characteristic patterns
      of gene expression that were chemical-specific, indicating that the Daphnia DNA
      microarray can be used for classification of toxic chemicals and for development
      of a mechanistic understanding of chemical toxicity on a common freshwater
      organism.

PMID- 17447552
TI  - Bioenergetic and pharmacokinetic model for exposure of common loon (Gavia immer)
      chicks to methylmercury.
AB  - A bioenergetics model was used to predict food intake of common loon (Gavia
      immer) chicks as a function of body mass during development, and a
      pharmacokinetics model, based on first-order kinetics in a single compartment,
      was used to predict blood Hg level as a function of food intake rate, food Hg
      content, body mass, and Hg absorption and elimination. Predictions were tested in
      captive growing chicks fed trout (Salmo gairdneri) with average MeHg
      concentrations of 0.02 (control), 0.4, and 1.2 microg/g wet mass (delivered as
      CH3HgCl). Predicted food intake matched observed intake through 50 d of age but
      then exceeded observed intake by an amount that grew progressively larger with
      age, reaching a significant overestimate of 28% by the end of the trial.
      Respiration in older, nongrowing birds probably was overestimated by using rates
      measured in younger, growing birds. Close agreement was found between simulations
      and measured blood Hg, which varied significantly with dietary Hg and age.
      Although chicks may hatch with different blood Hg levels, their blood level is
      determined mainly by dietary Hg level beyond approximately two weeks of age. The
      model also may be useful for predicting Hg levels in adults and in the eggs that
      they lay, but its accuracy in both chicks and adults needs to be tested in free
      living birds.

PMID- 17447553
TI  - Predicting metal uptake by wetland plants under aerobic and anaerobic conditions.
AB  - Metal pollution can be a serious threat to ecosystems at a global scale. Although
      the bioavailability of potentially toxic metals is determined by many biotic and
      abiotic factors, including pH and redox potential, total metal concentrations in
      the soil are used widely to assess or predict toxicity. In the present study we
      tested the effect of desiccation of soils differing in acidification potential
      and total heavy metal contamination on the growth and metal uptake of three
      typical, common wetland species: Caltha palustris, Juncus effusus, and Rumex
      hydrolapathum. We found that plant growth in wet soils mainly was determined by
      nutrient availability, though in dry soils the combined effects of acidification
      and increased metal availability prevailed. Metal uptake under anaerobic
      conditions was best predicted by the acidification potential (sediment S/[Ca +
      Mg] ratio), not by total metal concentrations. We propose that this is related to
      radial oxygen loss by wetland plant roots, which leads to acidification of the
      rhizosphere. Under aerobic conditions, plant metal uptake was best predicted by
      the amount of CaCl2-extractable metals. We conclude that total metal
      concentrations are not suitable for predicting bioavailability and that the above
      diagnostic parameters will provide insight into biogeochemical processes involved
      in toxicity assessment and soil policy.

PMID- 17447554
TI  - Evaluation of the reproductive effects of tamoxifen citrate in partial and full
      life-cycle studies using fathead minnows (Pimephales promelas).
AB  - Laboratory studies were conducted to investigate potential adverse effects on
      development, growth, reproduction and biomarker responses (vitellogenin [VTG] and
      gonad histology) in fathead minnows (Pimephales promelas) exposed to tamoxifen
      citrate. Based on the results of a partial life cycle study (nominal [mean
      measured] concentrations ranged from 0.18 [0.11] to 18 [15.74] microg/L), a 284-d
      fish full life-cycle (FFLC) flow-through study was conducted using newly
      fertilized embryos (<24 h postfertilization) exposed to nominal (mean measured)
      concentrations of 14C-tamoxifen citrate that ranged from 0.01 (0.007) to 5.12
      (4.08) microg/L. Triethylene glycol (2.0 microl/L) was used as a solvent carrier,
      with 17beta-estradiol (E2) as a positive control (nominal 0.1 microg/L). Among
      the biomarkers measured, significant effects on VTG and gonad histology were
      observed, although these results required care in their interpretation. Among
      important population-relevant endpoints, no effects on reproduction were observed
      at nominal concentrations < or = 5.12 microg/L. Effects on growth (length and
      weight) were observed in some treatments; however, some of these showed irregular
      concentration-response relationships, which made interpretation uncertain, or
      were deemed transient in nature (e.g., reduction in growth of F1 28-d posthatch
      larval fish at nominal concentrations of 0.08, 0.64, and 5.12 microg/L) and
      judged not to be biologically significant. Interpretation of results from fish
      chronic studies is challenging and frequently calls for scientific judgement
      about statistical and biological significance and what constitutes an adverse
      effect. Using the principles used in mammalian toxicology studies, data from
      partial and FFLC studies were evaluated from both statistical and biological
      perspectives in order to determine no-observed-adverse effect concentrations
      (expressed as (adverse)NOEC) for use in environmental risk assessment. Careful
      consideration of both biological and statistical outcomes from these studies
      suggested overall (adverse)NOEC concentration and lowest-observed-effect
      concentration ((adverse)LOEC) values for tamoxifen citrate of 5.12 microg/L and
      5.6 microg/L, respectively.

PMID- 17447555
TI  - Effect of carbon nanotubes on developing zebrafish (Danio rerio) embryos.
AB  - The impact of carbon nanotubes (CNTs) on the aquatic environment was investigated
      by examining the properties of raw CNTs under several environmental conditions
      and using developing zebrafish (Danio rerio) embryos. The agglomerate size for
      single-walled CNTs (SWCNTs) was significantly larger at pH 11 or greater and was
      stable at temperatures from 4 to 40 degrees C and salinities from 0 to 30 ppt.
      Exposure to SWCNTs induced a significant hatching delay in zebrafish embryos
      between 52 to 72 h postfertilization (hpf) at concentrations of greater than 120
      mg/L, but 99% of the exposed embryos hatched by 75 hpf. Double-walled CNTs also
      induced a hatching delay at concentrations of greater than 240 mg/L, but carbon
      black did not affect hatching at the concentrations tested. Molecular and
      cellular analysis showed that the embryonic development of the exposed embryos up
      to 96 hpf was not affected at SWCNT concentrations of up to 360 mg/L. Scanning
      electron microscopic inspection showed that the size of the pores on the embryo
      chorion was nanoscaled and that the size of SWCNT agglomerates was microscaled or
      larger, indicating that the chorion of zebrafish embryos was an effective
      protective barrier to SWCNT agglomerates. The hatching delay observed in this
      study likely was induced by the Co and Ni catalysts used in the production of
      SWCNTs that remained at trace concentrations after purification. This study
      suggests that materials associated with raw SWCNTs (perhaps metal contaminants)
      have the potential to affect aquatic life when released into the aquatic
      environment.

PMID- 17447556
TI  - Effects of proposed physical ballast tank treatments on aquatic invertebrate
      resting eggs.
AB  - Adaptations in aquatic invertebrate resting eggs that confer protection from
      natural catastrophic events also could confer protection from treatments applied
      to ballast water for biological invasion vector management. To evaluate the
      potential efficacy of physical ballast water treatment methods, the present study
      examined the acute toxicity of heat (flash and holding methods), ultraviolet (UV)
      radiation (254 nm), and deoxygenation (acute and chronic) on resting eggs of the
      freshwater cladoceran Daphnia mendotae and the marine brine shrimp Artemia sp.
      Both D. mendotae and Artemia sp. were similarly sensitive to flash exposures of
      heat (100% mortality at 70 degrees C), but D. mendotae were much more sensitive
      to prolonged exposures. Exposure to 4,000 mJ/cm2 of UV radiation resulted in
      mortality rates of 59% in Artemia sp. and 91% in D. mendotae. Deoxygenation to an
      oxygen concentration of 1 mg/L was maximally toxic to both species. Deoxygenation
      suppressed hatching of D. mendotae resting eggs at oxygen concentrations of less
      than 5.5 mg/L and of Artemia sp. resting eggs at concentrations of less than 1
      mg/L. Results suggest that UV radiation and deoxygenation are not viable
      treatment methods with respect to invertebrate resting eggs because of the
      impracticality of producing sufficient UV doses and the suppression of hatching
      at low oxygen concentrations. Results also suggest that the treatment
      temperatures required to kill resting eggs are much higher than those reported to
      be effective against other invertebrate life stages and species. The results,
      however, do not preclude the effectiveness of these treatments against other
      organisms or life stages. Nevertheless, if ballast tank treatment systems
      employing the tested methods are intended to include mitigation of viable resting
      eggs, then physical removal of large resting eggs and ephippia via filtration
      would be a necessary initial step.

PMID- 17447557
TI  - Effects of estrone on full life cycle of Java medaka (Oryzias javanicus), a new
      marine test fish.
AB  - Estrone is a natural estrogen detected in sewage treatment works effluents and in
      estuarine waters. However, there is little information on the effects of estrone
      on marine fish. This study investigated the effects of estrone on reproduction of
      the estuarine fish, Java medaka (Oryzias javanicus). Java medaka were exposed to
      concentrations of 39, 198, 484, 1,188, and 3,701 ng/L of estrone from embryonic
      stages up to adult stages for 239 d after hatching. The fertility and egg numbers
      of Java medaka exposed to 1,188 and 3,701 ng/L were significantly lower than that
      of control. The hepatic vitellogenin concentrations in male Java medaka exposed
      to estrone greater than 484 ng/L were significantly higher than that of control.
      Oocytes in testis (testis-ova) were not detected in the males in any of the
      exposure groups. The lowest-observed-effect concentration and no-observed-effect
      concentration for Java medaka were 484 and 198 ng/L of estrone. These results
      suggest that in relatively low estrone concentrations, 39 and 198 ng/L, Java
      medaka will not be affected by exposure to estrone.

PMID- 17447558
TI  - Effects of 17alpha-ethinylestradiol and bisphenol A on vertebral development in
      the fathead minnow (Pimephales promelas).
AB  - Growth, reproductive ability, and metabolic functions may be impaired by
      disruption of early endocrine patterning. Natural and synthetic estrogens
      detected in surface waters have been linked to reproductive endocrine signaling
      disruption in several species. The present study characterizes the
      nonreproductive morphological endpoint of vertebral anomalies in fish exposed to
      environmental estrogens. Estrogen is a proliferation-inducing compound in
      osteoblasts, regulating cartilage and bone deposition during development in
      vertebrates. The hypothesis for the present work is that xenobiotics with
      estrogenic activity adversely impact vertebral bone formation. Fathead minnows
      (Pimephales promelas) were exposed to 0.1 to 100 microg/L 17alpha
      ethinylestradiol (EE2) and 0.1 to 1,000 microg/L bisphenol A (BPA) from egg stage
      (24 h postfertilization) to 25 to 26 d posthatch. Fish were measured for length
      and analyzed microscopically to determine degree of skeletal development
      (developmental score) and the occurrence of spinal abnormalities, including
      vertebral compression, bone fusion, and spinal curvatures. Fish length and
      developmental score were inversely related to vertebral malformations in exposed
      fish. Skeletal developmental was affected significantly in EE2-exposed fish:
      Vertebral malformations were observed in up to 62% of fish in a nonmonotonic dose
      response. However, BPA did not significantly impair skeletal development or
      induce vertebral malformations. The bioassay results suggest vertebral bone
      development is a potential endpoint of endocrine disruption from potent
      estrogenic compounds in surface waters.

PMID- 17447559
TI  - Recovery of nontarget Lepidoptera on Vancouver Island, Canada: one and four years
      after a gypsy moth eradication program.
AB  - The gypsy moth (Lymantria dispar) is a destructive defoliator that is not
      established in British Columbia, Canada, because of successful eradication
      programs involving the microbial insecticide Bacillus thuringiensis var. kurstaki
      (Btk). In 1999, three aerial applications of Btk were made over two areas,
      totaling 12,805 ha, on southern Vancouver Island, Canada. The impacts of these
      Btk applications on nontarget Lepidoptera were studied from 1999 to 2004 on Garry
      oak (Quercus garryana) and common snowberry (Symphoricarpos albus). In 1999,
      lepidopteran larvae were collected from S. albus foliage at 24 urban parks and
      from Q. garryana foliage at 28 oak-dominated habitats. The initial impacts (i.e.,
      1999 data) were published previously, and the present paper is a continuation of
      the same study. We tested two hypotheses: Reductions of nontarget Lepidoptera
      would be more severe at 12 to 13 months postspray than at one to two months
      postspray, and recovery would be significant, though not necessarily complete, at
      four years postspray. The total number of nontarget Lepidoptera on S. albus and
      Q. garryana was significantly reduced in the treatment sites in each year of the
      study: the reduction was greatest in 2000. Relative to the reference sites, each
      of 11 species that were initially reduced by the Btk applications showed an
      increase in the treatment sites between 2000 and 2003, by which time only four
      species remained significantly reduced in the treatment sites. The uncommon
      species were significantly reduced in 1999 and 2000 but not in 2003, indicating
      that some recovery had occurred. Limitations and economic implications of the
      present study are discussed.

PMID- 17447560
TI  - Biodegradable chelating agent ethylenediaminedisuccinic acid reduces uptake of
      copper through alleviation of copper toxicity in hydroponically grown
      Chrysanthemum coronarium L.
AB  - Hydroponic cultures were conducted to investigate the effects of the
      biodegradable chelating agent S,S-ethylenediaminedisuccinic acid (EDDS) on the
      growth and copper uptake by garland chrysanthemum (Chrysanthemum coronarium L.),
      a plant species sensitive to soil chelate amendment. In the presence of 50
      micromol/L Cu, the addition of EDDS increased shoot and root biomass and the
      vitality of cells in root tips and decreased the relative electrolyte leakage of
      root cells and the concentration of Cu in shoots. When the roots were pretreated
      with 65 degrees C hot water for 0.5 to 2 h or with 0.001 to 0.1 mol/L HCl for 24
      h before the exposure to 50 micromol/L Cu + 100 micromol/L EDDS, the
      concentration of Cu in shoots increased considerably compared with the plants
      without any pretreatment. A statistically significant correlation was found
      between the Cu concentrations in shoots and the relative electrolyte leakage of
      root cells. These results indicated that Cu-EDDS might be a less bioavailable
      form to plants and that some physiological damage to the roots led to enhanced
      accumulation of Cu in plant shoots.

PMID- 17447561
TI  - Gut bacterial community structure (Porcellio scaber, Isopoda, Crustacea) as a
      measure of community level response to long-term and short-term metal pollution.
AB  - Prokaryotes are of high importance in the assessment of environmental pollution
      effects. Due to fast responsiveness of bacterial communities to environmental
      physicochemical factors, it is difficult to compare results of bacterial
      community investigations on the temporal and spatial scale. To reduce the effects
      of variable physicochemical environmental conditions on bacterial microbiota when
      investigating the specific impact of contaminants on bacterial communities, we
      investigated the bacterial community in the gut of terrestrial isopods (Porcellio
      scaber, Isopoda, Crustacea) from clean and metal-polluted environments. Animals
      were collected from a chronically mercury-polluted site, a chronically multiple
      metal-(Cd, Pb, Zn) polluted site, and two reference sites. In addition, animals
      from an unpolluted site were laboratory exposed to 5 microg Hg/g food in order to
      compare the effect of acute and chronic Hg exposure. The bacterial gut microbiota
      was investigated by temporal temperature gradient gel electrophoresis (TTGE) and
      clone library construction based on polymerase chain reaction amplified 16S rRNA
      genes. The major bacterial representatives of the emptied gut microbiota in the
      animals from the chronically polluted environments seemed not affected when
      analyzed by TTGE. The detailed bacterial community structure investigated by 16S
      rRNA clone library construction, however, showed that the community from the Hg
      polluted site also was affected severely (242.4 operational taxonomic units [OTU]
      in the polluted and 650.6 OTU in the unpolluted environment). When animals were
      acutely exposed to mercury, changes of bacterial community structures already
      were seen on TTGE profiles and no additional analysis was needed. We suggest the
      use of P. scaber gut bacterial community structure as a measure of effects caused
      by both long- and short-term exposure to pollution.

PMID- 17447562
TI  - Effects of brominated flame retardants and brominated dioxins on steroidogenesis
      in H295R human adrenocortical carcinoma cell line.
AB  - Brominated flame retardants (BFRs) and brominated dioxins are emerging persistent
      organic pollutants that are ubiquitous in the environment and can be accumulated
      by wildlife and humans. These chemicals can disturb endocrine function. Recent
      studies have demonstrated that one of the mechanisms of endocrine disruption by
      chemicals is modulation of steroidogenic gene expression or enzyme activities. In
      this study, an in vitro assay based on the H295R human adrenocortical carcinoma
      cell line, which possesses most key genes or enzymes involved in steroidogenesis,
      was used to examine the effects of five bromophenols, two polybrominated
      biphenyls (PBBs 77 and 169), 2,3,7,8-tetrabromodibenzo-p-dioxin, and 2,3,7,8
      tetrabromodibenzofuran on the expression of 10 key steroidogenic genes. The H295R
      cells were exposed to various BFR concentrations for 48 h, and the expression of
      specific genes--cytochrome P450 (CYP11A, CYP11B2, CYP17, CYP19, and CYP21), beta
      hydroxysteroid dehydrogenase (3betaHSD2), 17beta-hydroxysteroid dehydrogenase
      (17betaHSD1 and 17betaHSD4), steroidogenic acute regulatory protein (StAR), and 3
      hydroxy-3-methylglutaryl coenzyme A reductase (HMGR)--was quantitatively measured
      using real-time polymerase chain reaction. Cell viability was not affected at the
      doses tested. Most of the genes were either up- or down-regulated, to some
      extent, by BFR exposure. Among the genes tested, 3betaHSD2 was the most markedly
      up-regulated, with a range of magnitude from 1.6- to 20-fold. The results
      demonstrate that bromophenol, bromobiphenyls, and bromodibenzo-p-dioxin/furan are
      able to modulate steroidogenic gene expression, which may lead to endocrine
      disruption.

PMID- 17447563
TI  - Comparison of hardness- and chloride-regulated acute effects of sodium sulfate on
      two freshwater crustaceans.
AB  - Based on previous observations that hardness (and potentially chloride)
      influences sodium sulfate toxicity, the objective of the current study was to
      quantify the influence of both chloride and water hardness on acute toxicity to
      Hyalella azteca and Ceriodaphnia dubia. In addition, observed toxicity data from
      the present study were compared to toxicity predictions by the salinity/ toxicity
      relationship (STR) model. Hardness had a strong influence on sulfate toxicity
      that was similar for both crustaceans, and nearly identical median lethal
      concentration (LC50)/hardness slopes were observed for the two species over the
      tested range. Chloride had a strong but variable influence on sulfate acute
      toxicity, depending on the species tested and the concentration range. At lower
      chloride concentrations, LC50s for H. azteca strongly were correlated positively
      with chloride concentration, although chloride did not affect the toxicity of
      sodium sulfate to C. dubia. The opposite trend was observed over the higher range
      of chloride concentrations where there was a negative correlation between
      chloride concentration and sulfate LC50 for both species. The widely ranging
      values for both species and a high correlation between LC50s in terms of sulfate
      and conductivity suggested that, whether based on sulfate, conductivity, or total
      dissolved solids (TDS), attempts at water quality standard development should
      incorporate the fact that water quality parameters such as hardness and chloride
      strongly influence the toxicity of high TDS solutions. The STR model predicted
      toxicity to C. dubia relatively well when chloride was variable and hardness
      fixed at approximately 100 mg/L; however, the model did not account for the
      protective effect of hardness on major ion/TDS toxicity.

PMID- 17447564
TI  - Risk of weathered residual Exxon Valdez oil to pink salmon embryos in Prince
      William Sound.
AB  - It has been hypothesized that pink salmon eggs incubating in intertidal streams
      transecting Prince William Sound (PWS) beaches oiled by the Exxon Valdez oil
      spill were exposed to lethal doses of dissolved hydrocarbons. Since polycyclic
      aromatic hydrocarbon (PAH) levels in the incubation gravel were too low to cause
      mortality, the allegation is that dissolved high-molecular-weight hydrocarbons
      (HPAH) leaching from oil deposits on the beach adjacent to the streams were the
      source of toxicity. To evaluate this hypothesis, we placed pink salmon eggs in
      PWS beach sediments containing residual oil from the Exxon Valdez oil spill and
      in control areas without oil. We quantified the hydrocarbon concentrations in the
      eggs after three weeks of incubation. Tissue PAH concentrations of eggs in oiled
      sediments were generally < 100 ppb and similar to background levels on nonoiled
      beaches. Even eggs in direct contact with oil in the sediment resulted in tissue
      PAH loads well below the lethal threshold concentrations established in
      laboratory bioassays, and very low concentrations of HPAH compounds were present.
      These results indicate that petroleum hydrocarbons dissolved from oil deposits on
      intertidal beaches are not at concentrations that pose toxic risk to incubating
      pink salmon eggs. The evidence does not support the hypothesis that interstitial
      pore water in previously oiled beaches is highly toxic.

PMID- 17447565
TI  - Size-dependence of the potential for metal biomagnification in early life stages
      of marine fish.
AB  - We investigated the bioaccumulation of metals (Cd, Se, and Zn) in different
      juvenile sizes of black sea bream Acanthopagrus schlegeli by applying a
      biokinetic model. A series of experiments were conducted to determine the
      physiological kinetic parameters, including uptake rate constant of waterborne
      metals, ingestion rate, assimilation efficiency of dietary metals, efflux rate
      constant, and specific growth rate as a function of fish size. Body concentration
      of metals as a function of body size was then simulated by the kinetic model and
      compared with the actual measurements. The uptake rate constants decreased with
      increasing fish size, with an allometric exponent (b) of 0.615 to 0.662.
      Ingestion rate was also negatively correlated with the fish size (b = -0.604).
      Assimilation efficiencies of Cd were independent of body size, whereas those of
      Se and Zn increased with fish size. In contrast, efflux rate constants and growth
      rate constants for metals were comparable in different sizes of fish. Predicted
      concentrations of Cd and Zn were comparable to actual measurements and were
      negatively correlated with fish size. Ingestion rate was the most important
      parameter accounting for the size-dependent bioaccumulation of metals, followed
      by dietary assimilation. We further showed that the trophic transfer potentials
      of Se and Zn were > 1 in smaller fish but then reduced to < 1 in larger ones,
      suggesting that trophic transfer potentials are highly size dependent in marine
      fish.

PMID- 17447566
TI  - Deterministic and probabilistic acute-based environmental risk assessment for
      naproxen for western Europe.
AB  - An environmental risk assessment (ERA) was made for the common nonsteroidal anti
      inflammatory drug naproxen. The ERA was performed according to deterministic and
      probabilistic methods, based on different predicted environmental concentrations
      (PECs) and measured environmental concentrations (MECs) on the exposure side as
      well as on published and newly elaborated acute ecotoxicity data on the effects
      side. Compilation of a large set of MECs allowed a qualification of the various
      PEC derivations. The European Medicines Evaluation Authority (EMEA) phase I PEC
      was shown to be far above realistic values, while the refined EMEA phase II (A
      and B) PECs were not too far from the 95th percentile MEC, in agreement with
      their nature as local PECs. The western European continental and regional PECs
      extrapolated based on actual use data, using the European Union system for the
      evaluation of substances, with the region reconfigured for Germany where most of
      the available European MECs are from, were in good to very close agreement with
      the median MECs. No risk to surface waters is apparent by any of the
      methodologies applied from the current use of naproxen; however, because only
      insufficient chronic ecotoxicity data are available, this is a preliminary
      conclusion.

PMID- 17447567
TI  - Evaluating regional predictive capacity of a process-based mercury exposure
      model, regional-mercury cycling model, applied to 91 Vermont and New Hampshire
      lakes and ponds, USA.
AB  - Regulatory agencies must develop fish consumption advisories for many lakes and
      rivers with limited resources. Process-based mathematical models are potentially
      valuable tools for developing regional fish advisories. The regional mercury
      cycling model (R-MCM) specifically was designed to model a series of lakes for a
      given region with site-specific data and parameterization for each application.
      In this paper, we explore the feasibility of R-MCM application to develop
      regional fish advisories from existing data by testing model performance across
      91 Vermont ([VT], USA) and New Hampshire ([NH], USA) lakes. We use a progressive
      method of parameter refinement ranging from simple defaults specified by the
      model to site-specific parameterization to evaluate potential improvements in
      model prediction. Model applications and parameter refinement tiers are based on
      Regional Environmental Monitoring Assessment Program (REMAP) data. Results show
      that R-MCM generally underpredicts water column methylmercury and total mercury
      concentrations and overpredicts sediment methylmercury concentrations. Default
      level input parameterization produced the largest amount of random scatter in
      model forecasted values. Using site-specific values for the default level
      characteristics reduced this variability but did not improve overall model
      performance. By separating the observed and predicted data by lake
      characteristics, we identify some overall trends in bias and fit, but are unable
      to identify systematic biases in model performance by lake type. This analysis
      suggests that process-based models like R-MCM cannot be used for a priori
      predictive applications at the regional scale at this time. Further, this work
      reinforces the need for additional research on the transport and transformation
      of mercury to elucidate parameterization useable in a modeling framework to help
      refine predictive capabilities of process-based models.

PMID- 17447569
TI  - Evidence of causation.

PMID- 17447568
TI  - Quantitative structure-activity relationship modeling on in vitro endocrine
      effects and metabolic stability involving 26 selected brominated flame
      retardants.
AB  - In this work, quantitative structure-activity relationships (QSARs) were
      developed to aid human and environmental risk assessment processes for brominated
      flame retardants (BFRs). Brominated flame retardants, such as the high-production
      volume chemicals polybrominated diphenyl ethers (PBDEs), tetrabromobisphenol A,
      and hexabromocyclododecane, have been identified as potential endocrine
      disruptors. Quantitative structure-activity relationship models were built based
      on the in vitro potencies of 26 selected BFRs. The in vitro assays included
      interactions with, for example, androgen, progesterone, estrogen, and dioxin
      (aryl hydrocarbon) receptor, plus competition with thyroxine for its plasma
      carrier protein (transthyretin), inhibition of estradiol sulfation via
      sulfotransferase, and finally, rate of metabolization. The QSAR modeling, a
      number of physicochemical parameters were calculated describing the electronic,
      lipophilic, and structural characteristics of the molecules. These include
      frontier molecular orbitals, molecular charges, polarities, log octanol/water
      partitioning coefficient, and two- and three-dimensional molecularproperties.
      Experimental properties were included and measured for PBDEs, such as their
      individual ultraviolet spectra (200-320 nm) and retention times on three
      different high-performance liquid chromatography columns and one nonpolar gas
      chromatography column. Quantitative structure-activity relationship models based
      on androgen antagonism and metabolic degradation rates generally gave similar
      results, suggesting that lower-brominated PBDEs with bromine substitutions in
      ortho positions and bromine-free meta- and para positions had the highest
      potencies and metabolic degradation rates. Predictions made for the constituents
      of the technical flame retardant Bromkal 70-5DE found BDE 17 to be a potent
      androgen antagonist and BDE 66, which is a relevant PBDE in environmental
      samples, to be only a weak antagonist.

PMID- 17447570
TI  - Occupational Health risk and employment protection.

PMID- 17447571
TI  - Evaluation of individual susceptibility to noise-induced hearing loss in textile
      workers in China.
AB  - The authors applied noise exposure and audiometry information collected on 156
      Chinese textile workers to develop a method of identifying individuals
      susceptible to noise-induced hearing loss. They estimated noise-induced hearing
      threshold shift (NIHTS) by averaging the adjusted hearing thresholds at 3, 4, and
      6 kHz of both ears, and they fitted a quadratic model to describe the dose
      response relationship between cumulative noise exposure and NIHTS. The residual
      between the actual NIHTS and the model-predicted NIHTS indicated susceptibility.
      A comparison of the 20% of the subjects with the greatest residuals (those who
      were susceptible to hearing loss) with the 20% of the subjects with the smallest
      residuals (those who were resistant to hearing loss) revealed that the former had
      poorer hearing, although the noise exposures were similar. The identified
      susceptible individuals also had the poorest hearing thresholds within each
      subgroup of homogenous noise exposures. With their model-based procedure, the
      authors were able to identify individuals susceptible to noise-induced hearing
      loss from subjects with heterogeneous noise exposures.

PMID- 17447572
TI  - Tuberculosis among garment workers in an Arabian developing country: State of
      Qatar.
AB  - Tuberculosis (TB) continues to be a leading infectious cause of death worldwide,
      and it remains a serious public health problem in developing countries. To
      determine the prevalence of tuberculosis infection among garment workers, the
      authors conducted a retrospective prevalence survey of employees working in
      garment factories in Qatar from January 2000 to June 2003. A mass screening of
      garment factory workers was carried out by chest X-ray and Mantoux skin test at
      the Rumailah Hospital, Hamad Medical Corporation. The authors considered those
      workers with a purified protein derivative (tuberculin) reaction of > or = 15 mm
      to be infected with TB, or to have a latent TB infection. Workers with active TB
      diseases were confirmed by histopathological and mycobacteriological
      examinations. The authors studied a total of 2,774 garment factory workers, and
      they found 43% of them to be infected (reaction > or = 15 mm). The mean age of
      the infected subjects was significantly higher than that of the noninfected
      subjects (p < .001); 53% of the infected subjects were between 30 and 40 years of
      age. Indians and Pakistanis made up the most frequent nationalities among the
      infected subjects (50.0%), followed by Nepalis (44.1%). The prevalence rate of
      tuberculosis infection in garment workers was high. Overcrowding in factories and
      residential facilities increases the risk of TB transmission.

PMID- 17447573
TI  - Determinants of occupational disease incidence in Mexico.
AB  - Most occupational health researchers have studied individual determinants,
      tending to forget those causes that are universally present. To explore some
      determinants of occupational disease incidence in Mexico, the authors carried out
      an ecological study with data from 32 Mexican states. Using ordinary least
      squares regression, they explored associations between occupational disease
      incidence and the Gini coefficient, the percentage of small and median
      enterprises, and migration. Income inequality and the combined percentage of
      small and median enterprises were negatively associated with the incidence of
      occupational disease. In Mexico, the "population strategy" of the prevention of
      occupational disease suggests that big enterprises' contexts are related to a
      higher occurrence of occupational diseases. Further studies using multilevel
      approaches are needed to establish whether these occupational diseases are
      related to exposures present in big or in small and median enterprises.

PMID- 17447574
TI  - A case of Legionnaires' disease caused by aspiration of ice water.
AB  - The authors discuss the case of a 79-year-old patient who suffered from a
      swallowing disorder and developed Legionnaires' disease 2 days after her
      dismissal from an orthopedics ward, where she had recovered from hip surgery. To
      determine the source of the Legionnaires' disease, the authors performed an
      environmental investigation, which included a national, standardized
      questionnaire and a microbiological investigation of suspected sources. The
      investigation revealed ice from an ice-making machine in the hospital as the most
      probable source of the infection through aspiration, even though the hospital had
      rigorously adhered to strict assessment and decontamination schedules. The
      infectious serogroup was one that was not common to the area. From the data
      available, the authors inferred that a dose of 1-2000 colony-forming units might
      have caused Legionnaires' disease in this patient.

PMID- 17447575
TI  - Air pollution and respiratory hospital admissions in greater Paris: exploring sex
      differences.
AB  - The subject of sex and gender differences is relevant to the study of health
      effects of environmental exposures. In this study the authors aim at assessing
      the differences that may exist between males and females regarding short-term air
      pollution health effects. They studied the short-term relationships between air
      pollution levels and respiratory hospital admissions in greater Paris area for
      patients older than 15 years between 2000 and 2003. They also conducted time
      series analyses by using generalized additive models. For an increase of 10
      microg/m3 in the air pollutant levels, the increase in relative risk of
      hospitalization was higher for males than for females and was significant only
      for males. These differences may not result solely from differences in biological
      susceptibility to air pollution because other factors related to gender
      (differences in individual exposures, in health care management, and so on) may
      play a role.

PMID- 17447577
TI  - Iodine status of children living in areas with high nitrate levels in water.
AB  - Several researchers have suggested a possible relationship between nitrate intake
      and the development of goiter in children. The present cross-sectional study
      included schoolchildren between the ages of 11 and 14 years from 2 villages in
      Bulgaria with high and low nitrate levels in drinking water. The comparison
      between the median urinary iodine levels of the total number of exposed (179.0
      microg/l) and nonexposed (202.50 microg/l) children showed statistically
      significant differences. The relative risk for the children exposed to high
      nitrate levels in drinking water, expressed as the odds ratio, was 8.145 (95%
      confidence interval = 1.67-39.67). The authors considered this to be very
      significant. They found a statistically significant difference for the prevalence
      of goiter among the exposed and nonexposed children. The results of the study
      confirmed the role of high nitrate levels in drinking water as a health risk
      factor for thyroid dysfunction.

PMID- 17447576
TI  - Environmental exposure of a community to airborne trichloroethylene.
AB  - School officials and community citizens in Georgia were concerned about the
      airborne trichloroethylene (TCE) that was emanating from a nearby industrial
      facility that used TCE as a degreaser. No measurements of airborne TCE in the
      community were taken by public health officials or the industrial facility. The
      regulation of release of TCE from this facility was governed, in part, by
      mathematical model predictions of dispersion into the community. In support of
      community health concerns, the authors collected a limited number of outdoor and
      indoor air samples in the affected community, including those from a school, a
      small business, and three homes, for the analysis of TCE. The mean outdoor air
      concentration of TCE for all affected sites was 0.96 microg/m3 with a peak TCE
      concentration of 4.59 microg/m3. The mean indoor air concentration of TCE for all
      affected sites was 1.40 microg/m3 with a peak TCE concentration of 4.66
      microg/m3. All collected air samples were below the guideline level of 5 microg
      TCE/m3 of air as used by the state of Georgia in the United States, but sample
      levels were greater than those found in large population studies of TCE in indoor
      and outdoor air in Minnesota in the United States and in Ottawa in Canada.
      Additional air samples are needed to better characterize the exposure of the
      community to TCE.

PMID- 17447578
TI  - Microbial production and vaporization of mono-(2-ethylhexyl) phthalate from di-(2
      ethylhexyl) phthalate by microorganisms inside houses.
AB  - Laboratory workers were bothered by an irritation that caused coughing during the
      cultivation of microorganisms that degraded di-(2-ethylhexyl) phthalate (DEHP).
      The authors found that mono-(2-ethylhexyl) phthalate (MEHP), a known cause of
      asthma, was released during the degradation of DEHP. At its highest production
      and vaporization rate, the amount was almost equal to that of the DEHP starting
      material. It appeared that transport into the atmosphere depended on its
      adsorption on dust particles. The authors attempted to cultivate several
      microorganisms from house materials, especially those composed of rotting
      polyvinyl chloride. And microorganisms produced MEHP in the culture medium. In
      addition, MEHP was produced from DEHP by several stock microorganisms. Thus, MEHP
      could easily be produced from DEHP by microorganisms in the environment. In
      Japan, there are many cases of asthma with unknown causes. If MEHP is one of
      causes, then preventive measures against some cases of asthma could be taken.

PMID- 17447579
TI  - [Vitamin D--a sunny story. From a trivial vitamin to a possible actor in the
      pathogenesis of common diseases].

PMID- 17447580
TI  - [Vitamin D deficiency probably more common than earlier apprehended. Prevention
      and treatment could result in unexpected public health effects].

PMID- 17447581
TI  - [New evidence in SBU report on vitamin D and calcium. The risk of fracture is
      reduced by treatment in women older than 80 years--but not in younger ones].

PMID- 17447582
TI  - [Treatment of risk factors in critical extremity ischemia is important].

PMID- 17447583
TI  - [Do skiers in the long-distance ski race "Vasaloppet" really invest in their
      health?].

PMID- 17447584
TI  - [Deliberate disinformation on the tobacco issue].

PMID- 17447585
TI  - [Confirmed-by-law producer responsibility of tobacco industry can reduce the
      societal costs for the injuries].

PMID- 17447586
TI  - [Apolipoprotein determination was introduced without contribution of general
      practitioners--why?].

PMID- 17447587
TI  - [Go away Depo-Medrol!].

PMID- 17447588
TI  - [Falsified drugs hardly a threat against public health in Sweden].

PMID- 17447589
TI  - [The second letter from Baghdad].

PMID- 17447590
TI  - [Palliation in patients with metastatic breast cancer often better with
      antitumour treatment than with only symptomatic treatment].
AB  - Two women, aged 57 and 55 years, with metastatic breast cancer were admitted for
      uncontrolled pain due to bone metastases. Despite the fact that progressive
      disease was evident, a change in antitumour therapy had not been recommended. The
      pain control was optimised in both patients. In one patient, palliative
      chemotherapy was installed, combined with trastuzumab because of HER2/neu
      overexpression. She was still alive after one and a half year of treatment. The
      other patient could not adjust mentally to the fact that her palliative therapy
      was changed to antitumour therapy; she died one month later. It is important to
      be aware of the various kinds of therapy in metastatic breast cancer because
      palliative treatment is more than just symptomatic treatment. Systemic antitumour
      therapy includes hormone therapy, chemotherapy and targeted therapy. Furthermore,
      in patients with bone metastases, radiotherapy combined with bisphosphonates
      results in pain relief and can reduce skeletal complications. Because of the
      ensuing complexity of the treatment of metastatic breast cancer, these patients
      should be regularly managed by a breast-cancer care team in order to improve the
      quality of care.

PMID- 17447591
TI  - [Palliative care is more than palliative antitumour treatment and symptom
      management].
AB  - Nowadays, many palliative treatments are available for advanced cancer. These
      treatments provide relief of symptoms and add months to life, but their price is
      high, both literally and figuratively. Patients seize on any opportunity to be
      treated and oncologists find it hard to stop treatment because this means talking
      and reflecting about dying. This 'conspiracy of silence' makes it hard to say 'we
      don't have any further treatment'. Instead of saying 'we have no further
      treatment', patients should be offered palliative care as a positive choice to
      achieve the best quality of life, not only with physical but also with
      psychological, social and spiritual support.

PMID- 17447592
TI  - [Bias of results in clinical research due to method of informed consent].
AB  - Research ethics committees increasingly demand that investigators use an opt-in
      method (prior informed consent) to recruit their potential participants. Recent
      research has shown that opt-in systems of recruitment increase the response bias
      and reduce response rates. People willing to participate seem to find it
      burdensome to opt in. In contrast to this, public concern about an opt-out
      approach is minimal and will probably be outweighed by the potential harm caused
      by biased results from opt-in approaches. Concerns about protecting the rights of
      the individual should not override the importance of recruiting patients in
      medical research.

PMID- 17447593
TI  - [The pharmacokinetics of monoclonal antibodies].
AB  - Monoclonal antibodies (MOABs) are, due to their specificity, increasingly being
      deployed for therapeutic purposes. MOABs are derived from immunoglobulins and are
      fully or partially of murine or human origin. They are administered parenterally:
      mostly intravenously, but subcutaneous or intramuscular administration is also
      possible, in which case absorption probably occurs through the lymphatic system.
      The distribution of MOABs from the bloodstream into the tissues is slow and is
      hampered by the high molecular size of the MOABs, which is a lesser problem for
      fragments of antibodies (Fab fragments). MOABs are metabolised to peptides and
      amino acids. This process takes place in many tissues of the body, but probably
      predominantly in epithelial cells. As a consequence of the saturable binding of
      the MOAB to its target, a dose-dependent (non-linear) elimination is often
      observed. Immune reactions can accelerate the elimination of antibodies,
      partially depending on the degree ofhumanisation of the antibody. Antibodies and
      endogenous immunoglobulins are protected from elimination by binding to
      protective receptors (neonatal Fc-receptor; FcRn), which explains their long half
      lives (up to 4 weeks). Metabolic pharmacokinetic interactions with other drugs
      have not been reported and are not expected. It is expected that in the years to
      come, new MOABs directed towards new targets will appear on the market, as well
      as existing antibodies with improved pharmacokinetic properties.

PMID- 17447594
TI  - [A pseudo-outbreak of pharyngeal gonorrhoea related to a false-positive PCR
      result].
AB  - Nucleic acid amplification tests, including the polymerase chain reaction (PCR),
      are sensitive and specific tests that are often used for diagnosing sexually
      transmitted diseases (STDs). A pseudo-outbreak of pharyngeal gonorrhoea in a
      group of prostitutes turned out to have been caused by false-positive test
      results due to commensal oropharyngeal Neisseria species. Specific molecular
      tests may yield erroneous results. When the results of an STD study have major
      consequences at a legal or social level, it is advisable, in consultation with a
      medical microbiologist, to take a sample for culture or to carry out a second
      molecular test aimed at a different part of the bacterial genome.

PMID- 17447595
TI  - [From gene to disease; 'apparent mineralocorticoid excess' syndrome, a syndrome
      with an apparent excess of mineral corticoids].
AB  - Apparent mineralocorticoid excess (AME) is an autosomal recessive disease caused
      by deficiency of the enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta
      HSD2). 11beta-HSD2 converts cortisol into inactive cortisone and prevents the
      stimulation of the mineralocorticoid receptor by cortisol. In patients with AME,
      an enhanced stimulation of mineralocorticoid receptors by cortisol in the distal
      nephron causes an elevated sodium reabsorption and increased potassium excretion.
      Sodium retention leads to severe low renin hypertension. The diagnosis of AME is
      based on the detection of an increased concentration of cortisol metabolites and
      a low or undetectable concentration of cortisone metabolites in urine. Molecular
      analysis of the HSD11B2 gene confirms the diagnosis. AME is successfully treated
      by potassium-sparing diuretics, sometimes in combination with loop diuretics
      (furosemide). Mild forms of AME might occur more frequently than is currently
      known and should be suspected in patients with hypertension, hypokalemia and
      decreased plasma renin concentration. Since liquorice can induce the clinical
      symptoms of AME due to reversible inhibition of the 11beta-HSD2 enzyme by
      glycyrrhetinic acid, the active ingredient of liquorice, patients suspected of
      having AME should not consume liquorice.

PMID- 17447596
TI  - [Diagnostic image (316). A woman who died despite resuscitation. Pulmonary bone
      marrow embolism secondary to a sternum fracture].
AB  - A 75-year-old woman was unsuccessfully resuscitated. Post-mortem investigation
      showed pulmonary bone marrow embolism secondary to a sternum fracture probably
      caused by the external cardiac massage.

PMID- 17447597
TI  - [More potential organ donors than actual donations in 52 intensive-care units in
      the Netherlands, 2001-2004].
AB  - OBJECTIVE: To assess the number of potential organ donors and the main reasons
      why organ donation is not performed. DESIGN: Retrospective. METHOD: The number of
      potential heart-beating (HB) and non-heart-beating (NHB) donors was assessed by
      reviewing the medical records of 588o patients who died between 2001 and 2004 in
      52 intensive-care units (ICUs) in 30 hospitals. The number of actual donations
      was also assessed. RESULTS: The potential of HB donors was 2.5 to possibly 6.6%
      of all ICU deaths and HB donation was performed in 1.9% of all ICU deaths. The
      potential of NHB donors of category III was at least 4.2% of all ICU deaths and
      NHB donation was performed in 1.0% of all ICU deaths. The main difficulty in the
      donation process was objection from family members, which was reported in 45% of
      all potential HB and NHB donors and in 59% of all donation requests to relatives.
      Of the potential HB and NHB donors 7.3% were not identified as potential donors.
      CONCLUSION: These results confirm that organ-donor potential is greater than the
      number of actual donations. Objection from family members is the main limiting
      factor.

PMID- 17447598
TI  - [Endovascular prostheses and extra-anatomical bypasses to mesenteric and renal
      vessels in a patient with a thoraco-abdominal aortic aneurysm: a possible
      alternative to the standard operation].
AB  - A 57-year-old male had a thoraco-abdominal aortic aneurysm that was increasing in
      diameter, accompanied by pain in the right lower abdomen and groin. Ten years
      earlier he had had a dissecting thoraco-abdominal aneurysm that extended from the
      left subclavian artery to the aortic bifurcation. A CT-scan revealed further
      growth of the aneurysm. He was treated by an open and an endovascular operation.
      The distal aorta was replaced by a bifurcation prosthesis via a laparotomy, with
      2 other bifurcation prostheses to 2 mesenteric and 2 renal arteries. In a second
      session, a carotid-subclavian bypass was constructed and the aorta was reinforced
      by an endograft from the left subclavian artery to the bifurcation prosthesis.
      Postoperatively he suffered a transient ischaemic attack, hypertension,
      pneumonia, and vocal cord paresis. At follow-up 1.5 years later, the patient was
      free of symptoms, with the exception of slight hoarseness during forced speech,
      and the aneurysm was totally under control. This procedure may be an alternative
      to the classical thoracophrenicolaparotomy.

PMID- 17447599
TI  - [Subdural hygroma after falling down a staircase].
AB  - An 80-year-old man was admitted because of head trauma following a fall down a
      staircase. Initial CT-imaging of the brain showed only global atrophy, but
      repeated CT-imaging 4 days later revealed a subdural hygroma. Because of the
      discrepancy between the radiological deterioration and the unchanged neurological
      condition, we refrained from neurosurgical evacuation. Two months after the
      trauma, the subdural hygroma had been spontaneously resorbed, but neurological
      examination revealed severe residual neurological abnormalities. Subdural hygroma
      is a little known complication in the acute stage ofhead trauma, which is seen
      mainly in elderly patients. The pathophysiology is not well known.
      Differentiating subdural hygroma (cerebrospinal fluid (CSF) accumulation in the
      subdural space) from external hydrocephalus (excessive CSF accumulation in the
      subarachnoid space) is important in view of the therapeutic consequences. Because
      CT-imaging usually cannot differentiate between these 2 conditions, we recommend
      the use of MRI.

PMID- 17447600
TI  - [Medical perception of the hereditary aspects of cancer in The Netherlands, 1900
      1980].
AB  - Since at least the 18th century doctors have drawn connections between cancer and
      heredity in the hope of making progress in diagnosis, treatment and opportunities
      for prevention. From 1910 to 1980, the relationship between cancer and heredity
      was hardly discussed publicly in the Netherlands. This facilitated the
      development of models of public prevention and individual predisposition for
      certain cancers, such as retinoblastoma, after the Second World War. Historical
      experience shows that the perception of the relationship between cancer and
      heredity is influenced by more than just rational factors. The fear of creating
      'cancerphobia' has hindered this perception in the past; fatalism ('it makes no
      difference anyway') and stigmatisation (familial and societal pressure) may
      negatively influence participation in early detection and prevention. This
      remains a problematic issue today.

PMID- 17447601
TI  - [The electroshock has disappeared].

PMID- 17447602
TI  - [Hyperventilation has disappeared].

PMID- 17447603
TI  - [Palliative care in dementia and the dismantling of the treatment function of
      nursing homes].
AB  - Palliative care is mostly restricted to the terminal phase of incurable illness.
      According to the WHO revised definition palliative care is specifically directed
      towards patients and families facing life-threatening illness. This definition is
      not adequate to orient and direct palliative care policies in non-cancer diseases
      such as dementia. Although dementia is incurable from the outset, its course is
      often protracted, resulting in a terminal stage only after several years. This
      disease trajectory necessitates an alternative palliative approach, implying a
      proactive attitude of nursing home physicians in facilitating early and timely
      discussions with patients and their proxies on advance care planning and
      treatment of complications and concomitant diseases. This, together with their
      specific training in the treatment of the long-term sequelae of chronic diseases,
      defines the success of Dutch nursing home medicine in foregoing inappropriate
      hospital admissions and providing adequate medical care in the nursing home.
      However, recent reorganisations of nursing home care and its funding threaten to
      downgrade the quality of medical care for patients with dementia in Dutch nursing
      homes by focusing unilaterally on welfare ideology and 'marketization' of long
      term care, thus underestimating the importance of a palliative care policy in
      dementia.

PMID- 17447604
TI  - [A cross-cultural study of physician treatment decisions in relation to demented
      nursing home patients who develop pneumonia].
AB  - This qualitative interview study in The Netherlands and North Carolina (US) found
      that physician treatment decisions are influenced by contextual differences in
      physician training and healthcare delivery in the US and The Netherlands. Dutch
      physicians treating nursing home residents with dementia and pneumonia assumed
      active, primary responsibility for treatment decisions while US physicians were
      more passive and deferential to family preferences, even in cases where they
      considered the families' wishes inappropriate. Dutch physicians knew their
      patients well and made treatment decisions based on what they perceived was in
      the best interest of the patient while US physicians reported limited knowledge
      of their nursing home patients due to a lack of contact time. Efforts to improve
      care for patients with poor quality of life who lack decision-making capacity
      must consider the context of societal values, physician training, and the
      processes by which physicians negotiate patient and family preferences.

PMID- 17447605
TI  - [Sarcopenia as a component of "frailty"].

PMID- 17447606
TI  - [Small-scale group living for elderly with dementia: a clarification].
AB  - This article discusses the results of a Concept Mapping, held to clarify the
      concept of small-scale group living for elderly with dementia. Seventeen experts
      from different backgrounds formulated 91 statements about small-scale group
      living. These were subsequently depicted on a concept map with two dimensions:
      care versus living and individual versus context. The statements were then
      divided into six clusters by hierarchical cluster analysis. Five of these
      clusters centred around the arrangements of the individual lives of the residents
      and the collective lives of residents and staff, while only one held statements
      about the physical characteristics of small-scale group living. Therefore, it can
      be concluded from this Concept Map that small-scale group living is not so much
      determined by the physical characteristics but by the organisational features of
      the care context.

PMID- 17447607
TI  - [Mutual stereotypes of younger and older adults and their relation with self
      concept and self-esteem].
AB  - In this study younger and older persons were compared with regard to their
      stereotypes about both age groups, their self-concept and self-esteem. We
      examined the relation between age and stereotypes about younger and older adults,
      the relation between stereotypes about one's own age group and self-concepts, and
      the relation between self-concepts and self-esteem. Stereotypes and self-concepts
      were measured on two dimensions, warmth and competence. Twenty-eight younger
      adults (16-25 years) and 26 older adults (65-85 years) participated in this
      study. Both age groups perceived younger persons as more competent than older
      persons and older persons as more warm than younger persons. Older persons rate
      themselves higher than their in-group on competence and warmth. Younger
      respondents did the same, but on warmth only. A rating of the own person as more
      competent than the stereotype of their own age group, is related to self-esteem
      for older persons. Distancing oneself from negative stereotypes about one's own
      age group is an important key in maintaining high levels of self-esteem, but only
      in old age.

PMID- 17447608
TI  - [Anemia in the elderly: should it or should it not be treated?].

PMID- 17447609
TI  - [The psychometric properties of the Dutch version of the Telephone Interview
      Cognitive Status (TICS)].
AB  - The Telephone Interview Cognitive Status (TICS) is an instrument to screen for
      dementia in older persons by telephone. Although the psychometric properties of
      the TICS have been studied in various countries, the quality of the Dutch version
      of the TICS was yet unknown. This paper presents the Dutch version of the TICS
      and reports on its reliability and validity among 51 patients of Maastricht
      University Hospital, The Netherlands. The Pearson and intra-class correlations
      for test-retest reliability were 0.93 and 0.92, respectively. The Pearson and
      intra-class correlations for inter-rater reliability were 0.91 and 0.90,
      respectively. Sensitivity and specificity were studied in relation to the Mini
      Mental State Examination (MMSE, cut-off point 23/ 24) and the diagnosis of
      dementia as assessed according to DSM-IV criteria. When using the TICS cut-off
      point of 26/27, the coefficients for sensitivity and specificity were at least
      0.80. The percentages ROC under the curve were 90% and 93% with the MMSE and the
      diagnosis dementia as criterion, respectively. We conclude that the Dutch version
      of the TICS is an acceptable instrument for screening for dementia in older
      persons, particularly when face-to-face contact is not possible.

PMID- 17447610
TI  - [Advice research on medical care for the elderly. Especially the elderly with
      multiple and complex problems].

PMID- 17447611
TI  - Health diplomacy: winning hearts and minds through the use of health
      interventions.

PMID- 17447612
TI  - Tsunami overview.
AB  - Historically, floods and tsunamis have caused relatively few severe injuries; an
      exception to that tendency followed the great Andaman Island-Sumatra earthquake
      and tsunami of 2004. More than 280,000 people died, the coastal plains were
      massively scoured, and more than 1 million individuals were made homeless by the
      quake and resulting tsunami, which affected a 10-nation region around the Indian
      Ocean. This destruction overwhelmed local resources and called forth an
      unprecedented, prolonged, international response. The USNS Mercy deployed on a
      unique mission and rendered service to the people and government of Indonesia.
      This introduction provides background on the nature and extent of the damage,
      conditions upon arrival of the hospital ship 5 weeks after the initial
      destruction, and the configuration of professionals aboard (officers and sailors
      of the U.S. Navy, civilian volunteers from Project HOPE, officers of the U.S.
      Public Health Service, and officers and civilian mariners of the Military Sealift
      Command). Constraints on the mission provide context for the other articles of
      this issue that document and comment on the activities, challenges, methods, and
      accomplishments of this unique mission's "team of teams," performing humanitarian
      assistance and disaster relief in the Pacific theater.

PMID- 17447613
TI  - Rapid assessment of health needs and medical response after the tsunami in
      Thailand, 2004-2005.
AB  - On December 26, 2004, an earthquake triggered a massive tsunami in the Indian
      Ocean, causing an estimated 183,172 deaths and 40,320 missing in 12 countries. In
      Thailand, six provinces (Krabi, Phang-Nga, Phuket, Ranong, Satun, and Trang) were
      affected. U.S. government agencies delivered emergency medical assistance from
      December 30, 2004, to January 6, 2005. A team from the Armed Forces Research
      Institute of Medical Sciences conducted a rapid health and needs assessment in
      southern Thailand. Twelve hospitals were referral centers for tsunami-related
      medical care. None of the hospitals had been damaged during the tsunami; all
      activated mass casualty plans. As of October 2005, 5,395 deaths were confirmed
      and 2,817 individuals were missing. The response of the Thai government to the
      tsunami was rapid and effective in mitigating the health consequences among
      survivors and helped prioritize public health interventions and the diversion of
      U.S. assistance to areas with greater need for international emergency
      humanitarian assistance.

PMID- 17447614
TI  - Department of Defense Global Emerging Infections Surveillance and Response System
      Indian Ocean tsunami response.
AB  - The Department of Defense (DoD) Global Emerging Infections Surveillance and
      Response System (DoD-GEIS) identifies and addresses DoD vulnerabilities to
      emerging infections through a global network of partners. Following the Indian
      Ocean tsunami of December 26, 2004, DoD-GEIS facilitated the DoD medical response
      and coordination with the Centers for Disease Control and Prevention and the
      World Health Organization. DoD-GEIS partners in Southeast Asia (U.S. Naval
      Medical Research Unit 2, Jakarta, Indonesia; and Armed Forces Research Institute
      of Medical Sciences, Bangkok, Thailand) rapidly conducted health assessments and
      established surveillance for communicable diseases that threatened survivors.
      Preexisting collaboration with the Centers for Disease Control and Prevention,
      the World Health Organization, and host countries was critical for the DoD-GEIS
      tsunami response.

PMID- 17447615
TI  - Asian tsunami relief: Department of Defense public health response: policy and
      strategic coordination considerations.
AB  - The Asian tsunami of December 26, 2004, was one of the most devastating natural
      disasters in modern history. In particular, this disaster created massive,
      unique, public health threats, necessitating equally massive public health
      response efforts. The U.S. government (USG), including the Department of Defense
      (DoD), played a pivotal role in the response. This article examines some of the
      central policy issues and strategic coordination and planning measures involved
      in the public health response. The nearly unanimous consensus of international
      public health experts has been that the potential public health crisis in the
      aftermath of the Asian tsunami was averted largely because of the coordinated
      efforts of host nation officials and professionals, international and
      nongovernmental health organizations, and bilateral donors, especially the USG,
      including the DoD. The DoD played a central role in public health efforts through
      coordination and communication assistance, logistical and materiel support,
      disease surveillance activities, health needs assessments, and the contributions
      of the USS Mercy hospital ship. The core lessons involve the importance of an
      early, dedicated, public health response as a component of the overall disaster
      relief effort, as well as seamless coordination of health sector stakeholders in
      the USG and with those of the international community and affected host nations,
      which allows each organization to play to its strengths and to avoid duplication.
      The Asian tsunami relief effort highlighted the value of civil-military
      cooperation in disaster relief, particularly in the area of public health. The
      prominent role of the DoD in tsunami relief efforts, including public health
      efforts, also yielded beneficial secondary effects by bolstering security
      cooperation and winning "hearts and minds" in the region.

PMID- 17447616
TI  - Medical support to Sri Lanka in the wake of tsunamis: planning considerations and
      lessons learned.
AB  - When massive tsunamis affected the coast of Sri Lanka and other Indian Ocean
      littorals, elements of the Third Force Service Support Group and assigned Navy,
      Air Force, Army, and Coast Guard units from the U.S. Pacific Command were "task
      organized" to form Combined Support Group-Sri Lanka (CSG-SL), charged to conduct
      humanitarian assistance/disaster relief (HA/DR) operations. The specific mission
      was to provide immediate relief to the affected population of Sri Lanka and the
      Maldives, to minimize loss of life, and to mitigate human suffering. A 30-person
      health care team deployed to the northern province of Jaffna and provided medical
      assistance to that chronically underserved and acutely overstressed region. For a
      12-day period, the team served as the principal medical staff of an under
      resourced government hospital and conducted mobile primary care clinics at nearby
      welfare camps housing > 7,000 internally displaced persons made homeless by the
      tsunamis. By every measurable standard, CSG-SL accomplished its assigned HA/DR
      task in Sri Lanka, including the medical mission. In doing so, the medical team
      learned many important lessons, including five of particular value to planners of
      similar relief operations in the future. This article discusses the context in
      which CSG-SL planned and executed the medical aspects of its HA/DR operations in
      Sri Lanka, and it describes the most significant medical lessons learned.

PMID- 17447617
TI  - Combined Support Force 536: Operation Unified Assistance.
AB  - The coordinated and combined use of military and civilian resources in response
      to large-scale natural disasters have not been frequent or well documented.
      Historically, the overall efficacy and successes of such endeavors are mixed. The
      benefits of early decisive military leadership, time-phased implementation of
      resources, a stratified assistance program, and a working relationship is
      illustrated during the tragic Asian tsunami disaster of 2004 to 2005. The tasking
      of III Marine Expeditionary Force and my experience as Joint Task Force Surgeon
      suggest deliberate civil-military planning is beneficial and can significantly
      reduce human suffering.

PMID- 17447618
TI  - The Project HOPE and USNS Mercy tsunami "experiment".
AB  - A multifaceted, military-nongovernmental organization, public-private partnership
      was put together in 30 days to provide intermediate-stage medical support in
      response to the December 2004 tsunami. More than 200 civilian volunteer
      physicians, nurses, and medical professionals were recruited, oriented, and
      logistically supported by Project HOPE, an international nongovernmental
      organization, to serve aboard the hospital ship USNS Mercy off the coast of Banda
      Aceh, Indonesia, and subsequently in response to the related Nias Island
      earthquake. This "novel idea" resulted in tertiary care that was otherwise
      unavailable, expansion of the primary, dental, and optometric care available at
      the time, and Project HOPE programs on the ground that continue now, well after
      completion of the Navy mission. Furthermore, many of the members of this
      volunteer team would not have had the chance to participate as volunteers and
      would not have had exposure to the U.S. military, for which they have become
      staunch supporters. The "novel idea" of such a public-private partnership has met
      with a success that warrants doctrinal review for incorporation, programming, and
      planning to facilitate such engagement in the future.

PMID- 17447619
TI  - Perspectives from MTF USNS Mercy.

PMID- 17447620
TI  - Project HOPE volunteers and the Navy Hospital Ship Mercy.
AB  - This article describes, from the perspective of Project HOPE volunteers, the
      precedent-setting, military-civilian partnership in staffing the USNS Mercy as
      part of the rapid response of the United States to the overwhelming devastation
      and loss of life resulting from the tsunami off the coast of Indonesia. The
      article discusses the designation of Project HOPE as the non-governmental
      organization to be the single source of volunteers for the USNS Mercy mission
      (providing approximately 100 volunteers for each of two 30-day rotations), some
      issues facing Project HOPE and the contingent of volunteers in recruiting,
      orienting, training, and preparing for the mission, steps taken to make this a
      successful mission despite the ambiguity and uncertainties involved in arriving
      in the relief area 1 month after the disaster, and some recommendations for
      similar future missions. The Project HOPE volunteers quickly integrated with the
      cadre of Navy health professionals to deliver a broad range of high-quality care,
      including tertiary care, attesting to the professionalism and standards common to
      military and civilian medicine. The combined success of all organizations
      involved truly heralds a new era of medical diplomacy and goodwill in which the
      United States can take great pride.

PMID- 17447621
TI  - Massachusetts General Hospital participation in Operation Unified Assistance for
      tsunami relief in Banda Aceh, Indonesia.
AB  - When Project HOPE invited Massachusetts General Hospital (MGH) to participate in
      a tsunami relief mission aboard the USNS Mercy hospital ship in January 2005, MGH
      responded swiftly and enthusiastically. Overcoming differences in medical styles
      and standards, as well as a variety of cultural and institutional differences,
      MGH volunteers collaborated successfully with Navy personnel and volunteers from
      other hospitals to deliver excellent care to a large number of tsunami victims.
      Lessons were learned regarding the need for better initial team orientation, more
      open communication, and more-transparent decision-making; still, a rapid response
      of tertiary medicine, joining public and private resources, proved to be a
      powerful effective model.

PMID- 17447622
TI  - The virtual network supporting the front lines: addressing emerging behavioral
      health problems following the tsunami of 2004.
AB  - The devastation wreaked by the 2004 tsunami in the Indian Ocean required
      extensive multinational and nongovernmental relief efforts to address the massive
      loss of infrastructure, people, and society. This article addresses approaches to
      behavioral incident management from a process perspective, through the lens of
      one official stateside channel of emergency operations. The process highlights
      the formation and connectivity of multidisciplinary teams that virtually
      supported the efforts of a seven-person, on-scene, behavioral health team aboard
      the USNS Mercy as part of Operation Unified Assistance in the Indian Ocean.
      Frontline health diplomacy and behavioral health relief efforts were greatly
      augmented by the virtual network of support from leading experts around the
      globe. Future disaster response and recovery efforts ought to build on the
      success of such virtual support networks, by planning for appropriate technology,
      expertise, and mutual aid partnerships.

PMID- 17447623
TI  - Health diplomacy through collaboration and a story of hope in tsunami-ravaged
      Banda Aceh, Indonesia: A U.S. Public Health Service nurse officer perspective.
AB  - As a registered nurse, I have witnessed the powerful influence of bedside care
      for > 10 years. Yet my experience aboard the USNS Mercy--the first interagency
      deployment designed to provide humanitarian assistance to tsunami-stricken
      Indonesia--revealed a direct link between individual bedside care and health
      diplomacy. Despite desperate medical and humanitarian needs in the province of
      Banda Aceh, the Mercy was met with suspicion and resistance by the Indonesian
      government. In the first few days, it seemed uncertain that the Mercy would be
      asked to assist in any humanitarian capacity. The Mercy crew and staff agreed
      only to assist at the request of the Indonesian government. Ultimately it was the
      emergent medical needs of a 10-year-old survior, evacuated to the ship by
      Australian and German organizations, which established the seeds of health
      diplomacy between the United States and Indonesia. This article explores the ways
      in which health diplomacy can be fostered by individual medical and nursing care,
      through the story of one young survivor of the East Asian tsunami. My experience
      of compassionate and culturally centered care aboard the USNS Mercy touched the
      hearts and minds of care providers and, ultimately, won the trust of local
      government officials and the people of Banda Aceh.

PMID- 17447624
TI  - The USNS Mercy and the changing landscape of humanitarian and disaster response.
AB  - Operation Unified Assistance was the United States' historic response to the
      tsunami that struck Southeast Asia on December 26, 2004. The USNS Mercy
      participated in Operation Unified Assistance from January to March 2005.
      Stationed off the coast of Sumatra, Indonesia, the Mercy's crew consisted of
      uniformed members of the U.S. Navy and U.S. Public Health Service and civilian
      members of Project HOPE. The Mercy's participation in Operation Unified
      Assistance provided a platform and context to study disaster-related
      psychological processes. Observations of crew members aboard the Mercy suggested
      similar psychological processes for disaster victims and responders. Responder
      risk and protective factors; disaster responders as potential psychological
      casualties; responder selection, preparation, and intervention strategies; and
      the hospital ship as a research platform are discussed. Such issues are generally
      relevant to the interaction between civilian volunteers and professional disaster
      responders.

PMID- 17447625
TI  - Operation Unified Assistance population-based programs of the U.S. Public Health
      Service and international team.
AB  - The United States Public Health Service and several international relief agencies
      collaborated to create a series of programs for educational, governmental, and
      other behavioral health personnel in Aceh Province, Indonesia, following the
      tsunami of December 2004. This article provides a detailed account of the
      methodologies and approaches used to create the collaborations, as well as how
      they continue to be used by the people of Aceh through to this writing. Now known
      as the "Mercy Model," the approach represents a valuable set of programmatic
      approaches for rapidly developing and delivering large-scale behavioral health
      interventions in highly chaotic relief environments. It also details the
      potential benefits of using small teams on the ground, backed by much larger
      virtual teams to develop programming in real time across nations and continents,
      and do so in very short time frames.

PMID- 17447626
TI  - Lessons learned from Indonesia: an outline.
AB  - The U.S. response to the December 26, 2004 tsunami in Indonesia heralded
      modifications of our responses to previous natural disasters, modifications that
      were highly successful and should be refined and repeated. These included
      seamless hand-off of responsibility from a line response unit to medical; the use
      of civilian medical practitioners working closely with military and public health
      service personnel aboard a Navy vessel; close prior communication and planning
      with the local medical, governmental, and U.N. establishment ashore before the
      arrival of the military medical unit; and with both line and medical units
      working closely in support of established ashore U.N. agencies instead of
      performing independent actions. The success of this total approach was
      unquestioned, and the lessons learned should be utilized fully in planning future
      disaster responses, both foreign and domestic.

PMID- 17447627
TI  - "Just-in-time" mental health training and surveillance for the Project HOPE
      mission.
AB  - BACKGROUND: Immediately before the first sailing of the USS Mercy/Project HOPE
      relief mission to Southeast Asia, the mission leadership initiated presailing
      orientation and training and a program of survey-based health surveillance for
      mission participants. The training and surveillance efforts included a focus on
      mental health aspects of the mission. METHODS: At the conclusion of the
      predeployment mental health training, a voluntary, anonymous, predeployment
      survey was administered to members of the Project HOPE team. A second survey was
      administered approximately 3 months after return from the mission. The surveys
      were also administered before and after the second sailing of the USS
      Mercy/Project HOPE mission, although the training was not repeated. RESULTS: The
      sample size prevented statistical analysis of predeployment and postdeployment
      rates of illness; however, there was no evidence of incidence beyond population
      baseline rates. Responses to questions regarding perceptions of mission success
      and personal achievement were quite favorable, whereas specific questions
      regarding shipboard resources, training, and professional interactions were met
      with more variable responses. CONCLUSIONS: Response rates suggest a strong
      interest among participants in efforts to address the Project HOPE program and
      resources. They also suggest resilience among participants and areas for
      improvement in communication among participants.

PMID- 17447628
TI  - Civilian-military coordination in the emergency response in Indonesia.
AB  - Military and civilian humanitarian interventions in severely affected Indonesian
      province of Aceh are described following the tsunami of December 26. Specific
      events and activities illustrate the comparative roles of these types of agencies
      and how collaboration should recognize the abilities and limitations of each.

PMID- 17447629
TI  - Ovulation disorders: part I anovulation associated with estrogen deficiency.
AB  - PURPOSE: To describe the diagnosis and treatment of anovulatory disorders
      associated with estrogen deficiency. METHODS: Anovulation with estrogen
      deficiency was divided into two types: association with low vs. high serum
      gonadotropin levels. Treatments included bromocriptine or cabergoline for
      hyperprolactinemia and gonadotropins for normal prolactin levels. When
      gonadotropins were low, lowering the elevated serum FSH to restore down-regulated
      FSH receptors in the few remaining follicles with either ethinyl estradiol or
      GnRH agonists or antagonists was used. High serum FSH was followed by either
      close observation for spontaneous follicular maturation or low dose gonadotropin
      stimulation. Progesterone supplementation, especially by vaginal use, was given
      in the luteal phase. RESULTS: Though success in ovulation induction and
      pregnancies was greater in women with low FSH than high FSH, pregnancies
      following ovulation induction were nevertheless achieved even in women in
      apparent menopause. CONCLUSIONS: The use of ethinyl estradiol as opposed to other
      estrogen drugs has the advantage of not being able to be measured by most serum
      assays for estradiol allowing the physician to detect endogenous follicular
      development and thus determining when follicular maturation has been achieved.
      Even in the presence of marked diminished ovarian egg reserve, eggs from
      chronically younger women are superior in quality to women aged > or = 45.

PMID- 17447630
TI  - Low birth weight and early life origins of adult disease: insulin resistance and
      type 2 diabetes.

PMID- 17447631
TI  - Progesterone receptor expression by human leukocyte cell lines: molecular
      mechanisms of cytokine suppression.
AB  - PURPOSE: We investigated progesterone (P) signaling in human leukemia cells,
      shown to downregulate cytokines with P. METHODS: The following tests were
      utilized: PCR with FAM labeled primers and Gene Scan with the Applied Biosystems
      373 DNA sequencer for progesterone receptor (PR) mRNA, immunohistochemistry using
      monoclonal antibodies (Zymed and Ventana) for PR protein, RT-PCR for
      glucocorticoid receptor (GR), NFkappaB (p65, p50, p52), c-rel, IkappaB-alpha, c
      jun, c-fos, mRNA, transient transfections with pNF-kappaB-SEAP, and pGRE-SEAP
      vectors with chemiluminescence detection for NFkappaB and GR activity. RESULTS:
      PR transcripts were demonstrated in MOT, U937, K562, THP-1, 8226, U226, not in
      JUKAT, HL60, HUT102, isolated normal peripheral blood mononuclear cells, or
      purified CD4+ or CD8+ T cells. Estradiol increased PR mRNA in MOT and U937. MOT,
      U937, K562, KG-1, 8226, ATL, and CD8+HTLV-1 expressed PR protein. SRIH-BATL,
      729PH6NEO, HS-1, R-CLL, and JURKAT were negative. Steady state mRNA for GR,
      NFkappaB (p65, p50, p52), IkappaB-alpha, c-jun were unchanged with P in MOT and
      U937; c-fos and c-rel were not detected. There was a concentration-dependent
      reduction of NFkappaB activity with P in MOT and U937. CONCLUSION: The mechanism
      of cytokine suppression by P is mediated at least in part by suppression of
      NFkappaB, but the interaction of sex hormones, receptors, and transcription
      factors is complex.

PMID- 17447632
TI  - Luteal phase support for patients undergoing frozen-thawed embryo transfer cycles
      -the required progesterone dose.
AB  - OBJECTIVE: With the recent trend toward single-embryo transfer (ET),
      cryopreservation of extraneous embryos is becoming increasingly prevalent.
      Several replacement protocols for frozen-thawed ET exist, with no consensus
      regarding the dosage or delivery mode of progesterone. PATIENTS AND METHODS:
      Hormonal replacement with only estrogen and progesterone is the most frequently
      used protocol in women with and without functioning ovaries in our unit. Since
      August 2005, we have doubled the usual daily dose of progesterone for luteal
      support due to a high prevalence of patients experiencing withdrawal bleeding 11
      13 days after ET. We compared the outcome of frozen-thawed ET cycles using
      different doses of progesterone for luteal support. RESULTS: While the prevalence
      of embryos that survived the thawing process was significantly higher in the
      earlier (69%) as compared to the later period (58%), positive b-hCG pregnancy
      rates (17.5% vs 44.8%, respectively) and clinical pregnancy rates per transfer
      (7.9% vs 41.4%, respectively) were significantly higher in the later period.
      CONCLUSION: We conclude that high-dose progesterone supplementation in the luteal
      phase of frozen-thawed ET cycles results in a significantly higher clinical
      pregnancy rate.

PMID- 17447633
TI  - The influence of weather state on the incidence of preeclampsia and placental
      abruption in semi-arid areas.
AB  - BACKGROUND: Being close to the big deserts of the Sahara and Saudi Arabia, the
      Negev desert in the south of Israel is meteorologically defined as a semi-arid
      area. PURPOSE: To investigate the influence of meteorological factors typical for
      the semi-arid areas on the incidence of preeclampsia (PE) and placental abruption
      (PA). METHODS: The hospital records of women in confinement who had PE and/or PA
      between January 1, 1999 and December 31, 1999 were retrospectively reviewed. The
      current meteorological state was described by temperature, humidity, their
      overall differences and winds. Multivariate analysis, time series approach and
      Poisson regression are used. RESULTS: The incidence of PE and PA was increased
      during the periods of unstable weather. Strong winds were associated with
      increased frequency of PE (p < 0.002); desert wind of Sharav (specific
      atmospheric state and motion of big desert air volumes) increased incidence of PA
      (p < 0.033). Daily overall differences of temperature and humidity were
      correlated with PE (p < 0.03). An inverse correlation between humidity level and
      PA was obtained (p = 0.000). Increase in PE incidence preceded sharp variations
      in temperature with an average of 3-day lag (p < 0.003). CONCLUSIONS: An ensemble
      of meteorological variables, specific for each disorder, affects frequency of PA
      and PE occurrence. Obstetricians working in semi-arid areas should be aware of
      the influence of unstable weather conditions on the incidence of PE and PA,
      especially, in the spring and autumn seasons.

PMID- 17447634
TI  - High estradiol levels and depth of anaesthesia.
AB  - Estradiol is a steroid-structured hormone that has a periodic rhythm in the
      menstrual cycle. We aimed to evaluate the interference of high estradiol levels
      and the depth of anaesthesia. The study was performed on 44 females undergoing
      gynaelocologic surgery. Blood samples were performed for estradiol level before
      the procedures. BIS scores were recorded at 5-min intervals after induction and
      during the operation. Cases were assigned to three groups: Group 1 (n: 17)
      estradiol levels at or under 100 microg/dl, Group 2 (n: 14) levels were between
      100 and 200 microg/dl and Group 3 (n: 13) levels were above 200 microg/dl.
      Estradiol levels were found to be 59.94 +/- 23.59 microg/dl in Group 1, 138.60 +/
      23.49 microg/dl in Group 2 and 239.30 +/- 41.08 microg/dl in Group 3.
      Significant differences were found between initial control and 10 and 80 min BIS
      levels. Anaesthetic consumption showed a decreased tendency in high estradiol
      cases. We concluded that an advanced clinical series should be performed to fully
      define the relationship between estradiol levels and anaesthesia depth.

PMID- 17447635
TI  - Results after hysteroscopic management of premenopausal patients with
      dysfunctional uterine bleeding or intrauterine lesions.
AB  - AIM: The purpose of this study was to evaluate the efficacy, safety and benefits
      of hysteroscopic surgery in the management of dysfunctional uterine bleeding or
      intrauterine lesions causing menstrual disorders in premenopausal women. METHODS:
      We enrolled in this study 228 patients who underwent operative hysteroscopy
      because of metrorrhagia due to endometrial polyps or submucous myomas diagnosed
      by hysterosalpingography, transvaginal ultrasound and diagnostic hysteroscopy. In
      addition, the study population included 27 patients who presented dysfunctional
      uterine bleeding resistant to medical therapy. These patients underwent total or
      partial transcervical resection of endometrium (TCRE). RESULTS: Operative
      hysteroscopy was a successful procedure in 250 of the 255 cases (98%) but it
      needed to be repeated in three cases with large submucous myomas of type I and II
      and after two polypectomies. Mean duration of the procedure was 26.1 min (range 4
      58) and mean postoperative hospital stay was six hours (range 2-48 hours). There
      were two cases with fluid overload and five with postoperative uterine bleeding
      reported in this study. During postoperative follow-up (12-36 months) the
      majority of patients (246/255 or 96.5%) were free of symptoms. After total or
      partial TCRE, 23/27 patients (85.2%) reported eumenorrhea or hypomenorrhea, 2/27
      (7.4%) amenorrhea and 2/27 (7.4%) metrorrhagia (due to adenomyosis). CONCLUSION:
      Hysteroscopic surgery is an effective and safe method for the management of
      benign intracavitary pathology or the treatment of dysfunctional uterine
      bleeding. In addition, it has the advantages of quick recovery, early return to
      normal activities and reduced hospital stay for the patient. Careful monitoring
      of the patients avoids serious complications.

PMID- 17447636
TI  - Impact of tubal sterilization on women's health.
AB  - In this study we aimed to investigate the possible health effects of tubal
      sterilization on women who had chosen this method. A total of 127 women who had
      tubal sterilization between 2000-2005 were asked about their satisfaction with
      the method; their regrets and complaints, the effects of the tubal sterilization
      on their sexual life and their actual health. While 95% of the women were
      satisfied with the operation, only 76.9% of the patients would recommend this
      method to other woman. Although 23.1% reported changes in their sexual life after
      the sterilization, 30% reported changes in their menstrual cycle and 35% reported
      lower abdominal pain, two-thirds of the women did not state any significant
      complaint. Women who underwent the procedure at least two years before had fewer
      complaints; high school graduates and more educated women reported more changes
      in their sexual life. Women who had tubal sterilization were mostly satisfied
      with the method and were willing to recommend it to another woman.

PMID- 17447637
TI  - Biomagnetism in perinatal medicine. Our experience in Greece.
AB  - This is a report on our experience in the application of biomagnetism in
      perinatal medicine. We provide a brief description of our research work in fetal
      magnetoencephalography and fetal magnetocardiography in normal, preeclamptic and
      IUGR pregnancies, together with hemodynamics of the umbilical cord and uterine
      arteries, providing a new approach to biomagnetism as a non invasive imaging
      modality in the investigation of perinatal complications.

PMID- 17447638
TI  - Magnetic field profiles in normal human breast during the menstrual cycle.
AB  - OBJECTIVE: To investigate the subtle magnetic fields produced by living normal
      breast tissue during the menstrual cycle. METHODS: The magnetic activity of the
      breast was recorded in four young women, 26-28 years old; two had regular and two
      irregular menstrual cycles. The recordings were accomplished with a
      biomagnetometer and covered two complete menstrual cycles. The results were
      correlated with estrogen and progesterone levels on days 7, 14 and 21 of the
      menstrual cycle. RESULTS: The magnetic breast recordings in the two young women
      with the regular cycling endometrium showed a biphasic magnetic curve, apparently
      corresponding to the proliferative and secretory phase of the menstrual cycle. By
      contrast, the two young women with irregular menstrual cycles showed a monophasic
      magnetic curve. CONCLUSION: It is suggested that a biphasic, but not a
      monophasic, pattern of magnetic activity in the breast is indicative of an
      ovulatory endometrial cycle.

PMID- 17447639
TI  - Carbon dioxide laser treatment of Bartholin's gland cyst.
AB  - The purpose of this study is to present the results of laser surgery for
      Bartholin's cyst which shows to be a method that is safe, efficient, of low
      morbidity, and can be performed in an outpatient clinic under local anesthesia.
      Of the 22 cases operated on, only two had relapses which were resolved using a
      second procedure. The average surgery time was short, without bleeding during the
      operation. Complete epithelization was achieved within a maximum 4-week span with
      minimal or no postoperative discomfort.

PMID- 17447640
TI  - Effects of simultaneous treatment with estrogen and testosterone on the uterus of
      female adult rats.
AB  - BACKGROUND: Testosterone (T) associated with estrogen (E) has been used in
      hormonal replacement therapy in postmenopause women and the effects of this
      hormonal association on the uterus are not known. OBJECTIVE: To study the effect
      of long-term simultaneous exposure to testosterone and estrogen on the uterus of
      non-castrated adult female rats. METHODS: Groups of ten adult noncastrated female
      Wistar rats were treated with non-esterified testosterone and beta estradiol
      (subcutaneous implants with 50 mg of each hormone) or with testosterone cipionate
      and estradiol valerate (weekly intramuscularly or by subcutaneous injection of
      respectively, 2.85 mg/kg and 0.166 mg/kg). Control groups received no treatment
      (10 rats) or injections of diluents (6 rats). All animals were killed six months
      after hormonal exposure. RESULTS: All rats treated with T+E developed hyperplasia
      and hyperkeratosis of the vaginal and cervical epithelium and focal metaplasia
      with keratinization of the endocervical and endometrial epithelium. Ascending
      pelvic inflammatory disease with pyometra and tuboovarian abscesses were frequent
      (25% mortality until the end of the experiment). CONCLUSIONS: Testosterone
      associated with estrogen induced metaplasia of the genital epithelium but did not
      induce neoplastic lesions. The metaplasic lesions reduced the mucosal defense
      mechanisms enhancing ascending genital inflammatory disease. Although metaplasia
      of the cervical and endometrial epithelium has been observed after estrogen
      exposure in rats, testosterone does not appear to inhibit these estrogen effects.

PMID- 17447641
TI  - Dramatic relief of chronic pelvic pain with treatment with sympathomimetic amines
      -case report.
AB  - PURPOSE: To describe a novel treatment of chronic pelvic pain. METHODS:
      Dextroamphetamine sulfate was prescribed to a woman with unexplained chronic
      pelvic pain. Pelvic ultrasound, colonoscopy, and lower gastrointestinal
      radiographic studies were negative. Laparoscopy was offered as the next
      diagnostic test but the woman requested an attempt at medical therapy first.
      Based on previous experience of dramatic relief of chronic pelvic pain of bladder
      origin with sympathomimetic amine therapy she was started on dextroamphetamine
      sulfate. RESULTS: The relief of pain approximated 100% almost immediately and the
      pain relief has persisted for six months. Inadvertent failure to take the
      prescribed medication allowed the pain to return immediately only to disappear
      again once the medication was taken. CONCLUSIONS: Disorders of the
      sympathomimetic nervous system may be a cause of chronic pelvic pain and are
      relieved by treatment with sympathomimetic amines.

PMID- 17447642
TI  - Giant fibrothecoma--an interesting case.
AB  - A 45-year-old woman came for specialized medical attention due to intraabdominal
      pathology that began in 2003. Studies indicated the presence of a cyst in the
      right ovary, for which she was referred for surgery. She did not undergo the
      surgery and for a period of two years she suffered from an excessively enlarged
      abdomin. Posterior ultrasound studies indicated the presence of fibromatosis and
      she was again referred for surgery. Laparatomy was carried out and a giant cyst
      was found in the right ovary attached to the omentum, intestine, appendix,
      posterior side of the abdominal wall and to the uterus. We proceeded to remove
      the cyst and successively total abdominal hysterectomy and bilateral salpingo
      oophorectomy were performed. Post surgery, the patient progressed well taking
      pertinent prophylatic measures. The histopathology report diagnosed a giant
      fibrothecoma weighing 30 pounds, together with endometrial hyperplasia and
      leiomyomas. The international literature reports that the incidence of these
      tumors is low, 5% of ovarian tumors, and even lower for functioning tumors as in
      this case.

PMID- 17447643
TI  - Tricyclic antidepressant-induced acute urine retention in a young woman with
      postpartum depression--case report.
AB  - A rare case of acute urinary retention in a young woman due to simultaneous use
      of a tricyclic antidepressant and anticholinergic drugs is presented along with
      the data from the current literature, including the pharmacological action of
      these drugs, mainly focused on urological patients.

PMID- 17447644
TI  - Hydrosalpinx as an unusual complication of office hysteroscopy: case report.
AB  - Some complications of hysterocopy have been reported with increasing practice of
      the procedure both for diagnostic and operative procedures. However,
      complications associated with office hysteroscopy (HS) have not been well
      documented. A 35-year-old woman was accepted at our center for a second IVF
      cycle. She had had a history of primary infertility for nine years and no
      presumptive factors as a cause of infertility had been documented. Office
      hysteroscopy revealed a regular endocervix, endometrial cavity and bilateral
      internal tubal ostia. The patient was evaluated by pelvic examination (without
      any evidence of pelvic inflammatory disease) and transvaginal ultrasonograhy one
      month after the office HS for routine evaluation before the IVF cycle. There was
      an image compatible with left hydrosalpinx (6 mm in diameter) in her
      ultrasonographic examination that had not been detected before by the same
      physician using the same ultrasound equipment. Following an informative
      consultation with the patient, laparoscopy was performed and left hydrosalpinx
      was diagnosed. Salpingectomy was then carried out. The diagnosis of hydrosalpinx
      was confirmed by histological examination. To the best of our knowledge this is
      the first report of hydrosalpinx possibly caused by an office HS procedure.

PMID- 17447645
TI  - Endometriosis of ureter-induced recurrent urinary tract infections in a
      premenopausal woman--case report.
AB  - Endometriosis of the urinary tract is infrequent. The ureters and kidneys are the
      least usual place of localization. Endometriosis of the ureter often leads to
      silent loss of renal function due to delayed diagnosis. We report a case of a
      premenopausal female with endometriosis of the left distal ureter, presenting an
      infection of the urinary tract and having reported previous incidents of
      menorrhagia and left flank renal pain with automatic recession. Pharmacological
      treatment was applied with a satisfactory outcome. A short review of the
      literature is presented.

PMID- 17447646
TI  - First detection of IgA against norovirus in breast milk.
AB  - Breast milk samples (n = 239) collected from 1994-1997 from mothers at Chiba
      City, Japan, were tested for antinorovirus antibody by ELISA and western blot
      methods. It was found that 31 breast milk samples contained IgA against norovirus
      and this represented 13%. Breast milk could react with a diversity of norovirus
      genotypes. The highest number of samples containing IgA against norovirus was
      found in genotype GII/6 (11.3%) and the lowest in GI/8, GII/8 and GII/12 (each of
      0.8%). Of note, twenty-eight samples showed reactivity to more than one different
      norovirus genotypes. Interestingly, three samples demonstrated cross-reaction
      with both norovirus genogroups I and II. This report is noteworthy because it is
      the first, to the best of our knowledge, demonstrating the presence of antibody
      against norovirus in breast milk.

PMID- 17447647
TI  - Identification of antibody against porcine coronavirus in human milk.
AB  - A total of 239 human milk samples collected from mothers in Chiba City, Japan
      during 1994-1997 were tested for the presence of anti-coronavirus antibody.
      Interestingly, twelve human milk samples were positive for IgA against porcine
      transmissible gastroenteritis coronavirus, and this represented 5%. These
      findings provided evidence that the interspecies transmission of coronavirus
      between human and porcine might occur in nature. This report is noteworthy
      because it is the first, to the best of our knowledge, demonstrating the presence
      of antibody against porcine transmissible gastroenteritis coronavirus in human
      milk.

PMID- 17447648
TI  - Roche AMPLICOR human papilloma virus (HPV) and LINEAR ARRAY HPV tests will profit
      from automated DNA extraction.
AB  - BACKGROUND: Persistent infection with high risk human papillomavirus (HR-HPV)
      types is at the origin of cervical cancer in women and HPV-genotyping is
      considered to be a valuable tool for risk stratification. Its diagnostic
      relevance will further increase in the context of HPV vaccination which covers
      the HR-HPV types 16 and 18 only. For rapid screening and genotyping the
      commercial Roche AMPLICOR and the Roche LINEAR ARRAY (LA) HPV PCR tests are
      available. However, the manual DNA extraction procedure recommended by the
      manufacturer is time-consuming and labor-intensive. To improve workflow we
      evaluated automated DNA extraction by the MagNA Pure LC (MP-LC). CONCLUSION: The
      AMPLICOR and the LA HPV tests perform equally well with both extraction methods.
      The MagNA Pure LC provides an automated alternative for processing HPV clinical
      specimens coupled with the Roche AMPLICOR and LA HPV tests.

PMID- 17447649
TI  - The measurement of HIV-1 viral load in resource-limited settings: how and where?
AB  - There is an urgent need for low-cost, simple, and accurate human immunodeficiency
      virus type 1 (HIV-1) viral load monitoring technologies in resource-limited
      settings, particularly at the time of the scaling-up of first and second-line
      highly active antiretroviral therapies. This review describes the main
      characteristics and advantages/ disadvantages of three alternative HIV-1 viral
      load methods currently evaluated and used in developing countries, i.e., the
      Ultra p24 antigen assay, the ExaVir Load reverse transcriptase activity test, and
      'home-made' real-time PCR HIV-1 RNA techniques. This review discusses clinical
      results obtained with these three technologies in terms of correlation with
      commercial HIV-1 RNA assays, the impact of HIV-1 genetic diversity on
      quantification, as well as their usefulness for both the early diagnosis of
      pediatric HIV-1 infection and monitoring of highly active antiretroviral therapy
      efficiency. In addition, different strategies for HIV-1 viral load monitoring are
      discussed according to laboratory facilities in resource-constrained settings.

PMID- 17447650
TI  - Diagnostic evaluation of a new panel of assays for Epstein-Barr virus serology.

PMID- 17447651
TI  - Evaluation of a new ELISA for the detection of specific IgG to the Epstein-Barr
      nuclear antigen 1 (EBNA-1).
AB  - Diagnosis of acute primary Epstein-Barr Virus (EBV) infection is predominantly
      performed by serology. Detection of specific antibodies to defined EBV antigens
      is considered state of the art. Antibodies to EBNA-1 are not produced early in
      primary infection and a positive EBNA-1 serology is a sign of past infection.
      Therefore EBNA-1 serology plays a crucial role for EBV routine diagnosis. In the
      present study the quantitative EBV EBNA-1-IgG-ELISA PKS medac was evaluated
      regarding its suitability for routine diagnosis. Using clinically and
      diagnostically defined serum samples (141 from seronegative, 111 from acute
      infected, and 52 from individuals with past infection) as well as 100 sera from
      healthy blood donors the diagnostic performance of the assay was investigated.
      Furthermore, precision, performance of the single-point quantitation (SPQ), and
      suitability of the assay for automation were evaluated. Compared to the pre
      definition of the serum panel a sensitivity of 100% and a specificity of 99.6%
      was found. The measurement of the blood donor sera resulted in an anti-EBNA-1 IgG
      prevalence of 93% and an agreement of 99% with the results of a commercial ELISA
      used as reference. Regarding intra-assay variation, interassay variation
      (performed manually and automatically), and person-to-person variation a
      coefficient of variation < 10% was found with reactive samples. A good dilution
      linearity (r2 = 0.961), an excellent correlation of SPQ vs. the calibration curve
      (r2 = 0.997), and between the results of manually vs. automatically performed
      test runs (r2 > 0.995) was found. The evaluation has shown that the assay meets
      the demands of routine diagnosis very well.

PMID- 17447652
TI  - Platelet senescence and death.
AB  - The factors controlling the lifespan of platelets both in vivo and in vitro are
      poorly understood. What is known is that platelet aging in vivo leads to a
      reduction in the platelets' responsiveness to physiological agonists and that
      younger platelets are more haemostatically active than older ones. Under in vitro
      and ex vivo conditions platelets also lose function and ultimately die for
      reasons that are unclear, by mechanisms that share some similarity with those
      used by nucleated cells for programmed cell death. The consequences of platelet
      death in vitro include the formation of a novel platelet-platelet interaction
      that occurs between dead but not viable platelets and the shedding of the
      collagen receptor, GPVI and CD42b, a component of the von Willebrand receptor
      complex. Both of these phenomena appear to be regulated by metalloproteinase
      activity. In addition to these observations it is becoming increasingly clear
      that platelets execute a novel form of programmed cell death in response to
      agonists such as collagen and thrombin suggesting that their death is intimately
      associated with effective haemostasis. Finally, platelets must be removed from
      circulation. It is unclear how senescent platelets are removed, but monocyte
      macrophages are an important determinant of thrombus resolution possibly due to
      the phagocytosis of effete, activated platelets.

PMID- 17447653
TI  - A case of thrombosis of the superior mesenteric vein occurring in a young woman
      taking oral contraceptives: full and fast resolution with low molecular weight
      heparin.
AB  - Mesenteric venous thrombosis (MVT) is an unusual site of deep venous thrombosis.
      Little is known about risk factors of MVT, but available data seem to confirm a
      pathogenetic role of acquired thrombotic risk factors as well as inherited
      thrombotic risk factors. However, few cases on the association of MVT with oral
      contraceptive use have been described. We here report a case of MVT in a woman on
      oral contraception with fine and complete resolution after a fast diagnosis with
      abdominal ultrasound imaging and prompt therapy based on low molecular weight
      heparin.

PMID- 17447654
TI  - Lipid and lipoprotein profile in physiological pregnancy.
AB  - Physiologic pregnancy is associated with a broad series of metabolic adaptations
      which may also influence the metabolism of lipids and lipoproteins. Although the
      modification of serum lipids and lipoproteins has been exhaustively investigated
      during and after pregnancy, the relative changes recorded vary widely among the
      different studies. A comprehensive lipid and lipoprotein profile was evaluated in
      57 women with uncomplicated pregnancies at different gestational ages (20 in the
      first, 20 in the second, and 17 in the third trimester of pregnancy) and compared
      to that of 21 non-pregnant women. Conventional lipid parameters, including total
      cholesterol, high-density lipoprotein cholesterol and triglycerides, were
      evaluated on the Modular System P. Low-density lipoprotein cholesterol was
      quantified by the formula of Friedewald, the atherogenic index of plasma was
      quantified by the formula log (triglycerides/high-density lipoprotein
      cholesterol), whereas lipoprotein(a) was assayed on the BN II nephelometric
      analyzer. We observed that all the lipid parameters tested were significantly
      modified by the gestational age; in particular, women in the second and third
      trimester displayed significantly increased total cholesterol, low-density
      lipoprotein cholesterol, high-density lipoprotein cholesterol, total to high
      density lipoprotein cholesterol ratio, lipoprotein(a) and atherogenic index of
      plasma (third trimester only) when compared to either the control population or
      the subgroup of women in the first trimester of pregnancy. The value
      distributions and the relative percentage of women with undesirable or abnormal
      values according to the current NCEP or AHA/ACC goals were comparable between
      controls and women in the first trimester. However, when compared with either
      controls or women in the first trimester, advanced pregnancy was associated with
      an increased prevalence of undesirable or abnormal values for total cholesterol,
      low-density lipoprotein cholesterol and triglycerides in the second trimester,
      and total cholesterol, low-density lipoprotein cholesterol, triglycerides, total
      to high-density lipoprotein cholesterol ratio and lipoprotein(a) (only from non
      pregnant women) in the third trimester. The results of this case-control study
      demonstrate that physiological pregnancy is associated with a substantial
      modification of the lipid and lipoprotein metabolism from the second trimester,
      providing reference ranges for traditional and emerging cardiovascular risk
      predictors throughout the gestational period.

PMID- 17447655
TI  - Evaluation of conditions associated with glycated hemoglobin values below the
      reference range.
AB  - BACKGROUND: Evaluation of conditions associated with glycated hemoglobin (HbA1c)
      values below the reference range in HbA1c determinations. METHODS: Over a time
      period of 5 years, HbA1c results were determined with the ion-exchange high
      performance liquid chromatography (HPLC) method HA-8140 Menarini. RESULTS: Of
      approximately 20 000 HbA1c results analyzed, 9 were below the reference range.
      The reason for HbA1c values below the reference range was found to be liver
      cirrhosis in 6 patients, anemia with hematological neoplasms in 2 patients, and
      elevated fetal hemoglobin > 1.5% in one patient. The silent hemoglobin (Hb)
      variant Hb Graz in 6 patients, Hb Sherwood Forest in 1 patient, homozygote HbS in
      one patient, and gross hypertriglyceridemia in one patient demonstrated no HbA1c
      result. CONCLUSIONS: In patients with liver cirrhosis, HbA1c measurements should
      be used with caution when evaluating long-term glucose control, and samples with
      suspected Hb variants should be analyzed by hemoglobin electrophoresis. Our study
      underscores the need for clinical laboratories and physicians to be aware of the
      limitations of their HbA1c assay methods as well as of the importance of visual
      inspection of ion-exchange chromatograms to detect HbA1c values below the
      reference range and abnormalities caused by the interference factors described
      here.

PMID- 17447656
TI  - Can an ELISA replace immunofluorescence for the detection of anti-nuclear
      antibodies?--The routine use of anti-nuclear antibody screening ELISAs.
AB  - The aim of this study was to evaluate a commercially available ELISA assay for
      anti-nuclear antibodies (ANA) screening in a large routine laboratory setting.
      The detection of ANA is a commonly requested test by clinicians for patients
      suspected of rheumatic disease and other connective tissue diseases. Detection is
      part of the diagnostic criteria of rheumatic diseases such as SLE and can be
      important for monitoring purposes. ANA screening assays are typically indirect
      immunofluorescence (IIF), either on rodent tissue or HEp-2 cells; however, these
      are slow, subjective and laborious. In this study, in a routine serology
      laboratory setting, 2000 consecutive sera with requests for an ANA screen were
      tested by ELISA and results compared to those obtained by immunofluorescence.
      From these results we established an ANA ratio cut-off protocol to guide further
      action, a second series of 7000 samples was studied to assess the efficacy of
      this. Results show that the ANA ELISA can successfully replace IIF for the
      detection of clinically significant antibodies.

PMID- 17447658
TI  - Oxidative stress and role of antioxidant supplementation in critical illness.
AB  - Sepsis or systemic inflammatory response (SIRS) to infection or to non-infectious
      stimuli such as trauma, surgery, pancreatitis or ischemia, is an increasingly
      common cause of morbidity and mortality in patients on intensive therapy unit
      (ITU). In critically ill patients, this accounts for 10% to 50% of all deaths.
      Oxidative stress has an important role in the development and manifestations of
      SIRS. Oxidative stress is an imbalance between the free radical production and
      the antioxidant defense. In critical illness, overwhelming inflammatory mediator
      response to infective or non-infective stimuli results in excessive production of
      free radicals (FR). The action of FR is normally limited by the antioxidant
      defense system of the body, but in critically ill patients the antioxidant
      capacity is likely to be compromised. Hence, provision of antioxidants to
      critically ill patients may help in removing the FR and therefore improving the
      clinical outcome. However, no study has yet provided conclusive evidence of the
      beneficial effect of antioxidant supplementation in critically ill patients. The
      clinical evidence provided so far shows that there are several factors which
      might determine the efficacy of antioxidant supplementation in critically ill
      patients. There is a need for large multicentre prospective randomized control
      trials to assess the effects of different types and doses of antioxidant
      supplementation in selected groups of patients with different types of critical
      illness.

PMID- 17447657
TI  - Relaxin expression correlates significantly with serum changes in VEGF in
      response to antidiabetic treatment in male patients with type 2 diabetes
      mellitus.
AB  - Recent studies indicate that relaxin as well as VEGF possess cardioprotective
      properties. This study aimed to determine the association of relaxin with VEGF in
      patients with type 2 diabetes. We therefore analyzed samples from a recent study
      showing the benefits of anti-diabetic treatment on cardiovascular risk markers
      independently from glycemic control. VEGF, relaxin and markers of endothelial
      dysfunction, s-ICAM-1 and s-VCAM-1, were compared after 26 +/- 2 weeks of
      antidiabetic treatment with pioglitazone or glimepiride with their base line
      values. A total of 151 data sets (patients age, 62.7 +/- 8.1 years, diabetes
      duration, 6.8 +/- 6.6 years, 57 women, 94 men) were available for the analysis.
      Baseline values were in median, relaxin: 27.4 pg/mL 125% quartile 15.8; 75%
      quartile: 45.21, s-ICAM-1: 294 ng/mL [25% quartile: 260; 75% quartile: 331], s
      VCAM-1: 677 ng/mL [25% quartile: 589; 75% quartile 871], VEGF: 350 pg/mL [25%
      quartile: 251; 75% quartile: 514]. Parameter variation after therapy showed a
      significant correlation of relaxin expression with VEGF expression (p = 0.02) in
      the entire study group. The correlation was seen in the subgroup of male patients
      (p < 0.01) but did not reach significance in the female patients (p = 0.71). No
      further correlation was observed analyzing the other investigated parameters. Our
      data suggest that relaxin may exert its cardioprotective action possibly via VEGF
      increase, particularly in men. In women, other pathways may superimpose this
      effect. In conclusion, our study supports the hypothesis of different regulating
      pathways and effects of relaxin in men and women also in patients with type 2
      diabetes.

PMID- 17447659
TI  - Practical solution for control of the pre-analytical phase in decentralized
      clinical laboratories for meeting the requirements of the medical laboratory
      accreditation standard DIN EN ISO 15189.
AB  - This report was written in response to the article by Wood published recently in
      this journal. It describes a practical solution to the problems of controlling
      the pre-analytical phase in the clinical diagnostic laboratory. As an indicator
      of quality in the pre-analytical phase of sample processing, a target analyte was
      chosen which is sensitive to delay in centrifugation and/or analysis. The results
      of analyses of the samples sent by satellite medical practitioners were compared
      with those from an on-site hospital laboratory with a controllable optimized pre
      analytical phase. The aim of the comparison was: (a) to identify those medical
      practices whose mean/median sample values significantly deviate from those of the
      control situation in the hospital laboratory due to the possible problems in the
      pre-analytical phase; (b) to aid these laboratories in the process of rectifying
      these problems. A Microsoft Excel-based Pre-Analytical Survey tool (PAS tool) has
      been developed which addresses the above mentioned problems. It has been tested
      on serum potassium which is known to be sensitive to delay and/or irregularities
      in sample treatment. The PAS tool has been shown to be one possibility for
      improving the quality of the analyses by identifying the sources of problems
      within the pre-analytical phase, thus allowing them to be rectified.
      Additionally, the PAS tool has an educational value and can also be adopted for
      use in other decentralized laboratories.

PMID- 17447660
TI  - Sample commutability in external quality assessment surveys (EQAS) for thyroid
      related antibodies--state of the art.
AB  - External quality assessment surveys for thyroid-related antibodies have been
      offered by INSTAND for 20 years. During this time, some problems have remained,
      especially those between the similarity of samples sent and routine patient
      samples. Here the questions of "matrix effects" and "commutability of results"
      are topics discussed at most EQA-meetings. This short communication deals with
      the effects of lyophilization on results for thyroid-associated antibodies in an
      EQA-survey carried out by over 230 participants in October 2005 by INSTAND in
      Dusseldorf, Germany. The results show that there are small but statistically
      significant differences (at the level p < 0.05) in results from liquid and
      lyophilized samples from the same source, the tendency to higher results in the
      lyophilized samples for anti-TPO and anti-Tg and to lower results for TRAb. The
      precision in measurement was significantly better for anti-TPO and TRAb in the
      lyophilized samples, there being no significant difference for anti-Tg. The
      differences in results between liquid and lyophilized samples were minimal when
      compared with the numerical results for anti-TPO and anti-Tg, despite the fact
      that all kits were calibrated with the NIBSC reference materials, although the
      latter are now both 40 years old.

PMID- 17447661
TI  - Doctors are more dangerous than gun owners: a rejoinder to error counting.
AB  - OBJECTIVE: This paper analyzes some of the problems with error counting as well
      as the difficulty of proposing viable alternatives. BACKGROUND: Counting and
      tabulating negatives (e.g., errors) are currently popular ways to measure and
      help improve safety in a variety of domains. They uphold an illusion of
      rationality and control but may offer neither real insight nor productive routes
      for improving safety. METHOD: The paper conducts a critical analysis of
      assumptions underlying error counting in human factors. RESULTS: Error counting
      is a form of structural analysis that focuses on (supposed) causes and
      consequences; it defines risk and safety instrumentally in terms of minimizing
      negatives and their measurable effects. In this way, physicians can be proven to
      be 7500 times less safe than gun owners, as they are responsible for many more
      accidental deaths. CONCLUSION: The appeal of error counting may lie in a naive
      realism that can enchant researchers and practitioners alike. Supporting facts
      will continue to be found by those looking for errors through increasingly
      refined methods. APPLICATION: The paper outlines a different approach to
      understanding safety in complex systems that is more socially and politically
      oriented and that places emphasis on interpretation and social construction
      rather than on putatively objective structural features.

PMID- 17447662
TI  - Development and validation of Aviation Causal Contributors for Error Reporting
      Systems (ACCERS).
AB  - OBJECTIVE: This investigation sought to develop a reliable and valid
      classification system for identifying and classifying the underlying causes of
      pilot errors reported under the Aviation Safety Action Program (ASAP).
      BACKGROUND: ASAP is a voluntary safety program that air carriers may establish to
      study pilot and crew performance on the line. In ASAP programs, similar to the
      Aviation Safety Reporting System, pilots self-report incidents by filing a short
      text description of the event. The identification of contributors to errors is
      critical if organizations are to improve human performance, yet it is difficult
      for analysts to extract this information from text narratives. A taxonomy was
      needed that could be used by pilots to classify the causes of errors. METHOD:
      After completing a thorough literature review, pilot interviews and a card
      sorting task were conducted in Studies 1 and 2 to develop the initial structure
      of the Aviation Causal Contributors for Event Reporting Systems (ACCERS)
      taxonomy. The reliability and utility of ACCERS was then tested in studies 3a and
      3b by having pilots independently classify the primary and secondary causes of
      ASAP reports. RESULTS: The results provided initial evidence for the internal and
      external validity of ACCERS. Pilots were found to demonstrate adequate levels of
      agreement with respect to their category classifications. CONCLUSIONS: ACCERS
      appears to be a useful system for studying human error captured under pilot ASAP
      reports. Future work should focus on how ACCERS is organized and whether it can
      be used or modified to classify human error in ASAP programs for other aviation
      related job categories such as dispatchers. APPLICATION: Potential applications
      of this research include systems in which individuals self-report errors and that
      attempt to extract and classify the causes of those events.

PMID- 17447663
TI  - A self-report critical incident assessment tool for army night vision goggle
      helicopter operations.
AB  - OBJECTIVE: The present study sought to examine the utility of a self-report tool
      that was designed as a partial substitute for a face-to-face cognitive interview
      for critical incidents involving night vision goggles (NVGs). BACKGROUND: The use
      of NVGs remains problematic within the military environment, as these devices
      have been identified as a factor in a significant proportion of aircraft
      accidents and incidents. The self-report tool was structured to identify some of
      the cognitive features of human performance that were associated with critical
      incidents involving NVGs. The tool incorporated a number of different levels of
      analysis, ranging from specific behavioral responses to broader cognitive
      constructs. METHOD: Reports were received from 30 active pilots within the
      Australian Army using the NVG Critical Incident Assessment Tool (NVGCIAT).
      RESULTS: The results revealed a correspondence between specific types of NVG
      related errors and elements of the Human Factors Analysis and Classification
      System (HFACS). In addition, uncertainty emerged as a significant factor
      associated with the critical incidents that were recalled by operators.
      CONCLUSION: These results were broadly consistent with previous research and
      provide some support for the utility of subjective assessment tools as a means of
      extracting critical incident-related data when face-to-face cognitive interviews
      are not possible. APPLICATION: In some circumstances, the NVGCIAT might be
      regarded as a substitute cognitive interview protocol with some level of
      diagnosticity.

PMID- 17447664
TI  - A methodology for identifying human error in U.S. Navy diving accidents.
AB  - OBJECTIVE: To better understand how human error contributes to U.S. Navy diving
      accidents. BACKGROUND: An analysis of 263 U.S. Navy diving accident and mishap
      reports revealed that the human factors classifications were not informative for
      further analysis, and 70% of mishaps were attributed to unknown causes; only 23%
      were attributed to human factors. METHOD: Five diving fatality reports were
      examined using the consensual qualitative research (CQR) method to develop a
      taxonomy of six categories and 21 subcategories for classifying human errors in
      diving. In addition, 15 critical incident technique (CIT) interviews were
      conducted with U.S. Navy divers who had been involved in a diving accident or
      near miss and analyzed using the dive team error taxonomy. RESULTS: Overall,
      failures in situation awareness and leadership were the most common human errors
      made by the dive team. CONCLUSION: The dive team human error taxonomy could aid
      in accident investigation and in the training and evaluation of U.S. Navy divers.
      APPLICATION: The development of the dive team human error taxonomy has generated
      a number of considerations that researchers should take into account when
      developing, or adapting, an error taxonomy from one industry to another.

PMID- 17447665
TI  - Human error and commercial aviation accidents: an analysis using the human
      factors analysis and classification system.
AB  - OBJECTIVE: The aim of this study was to extend previous examinations of aviation
      accidents to include specific aircrew, environmental, supervisory, and
      organizational factors associated with two types of commercial aviation (air
      carrier and commuter/ on-demand) accidents using the Human Factors Analysis and
      Classification System (HFACS). BACKGROUND: HFACS is a theoretically based tool
      for investigating and analyzing human error associated with accidents and
      incidents. Previous research has shown that HFACS can be reliably used to
      identify human factors trends associated with military and general aviation
      accidents. METHOD: Using data obtained from both the National Transportation
      Safety Board and the Federal Aviation Administration, 6 pilot-raters classified
      aircrew, supervisory, organizational, and environmental causal factors associated
      with 1020 commercial aviation accidents that occurred over a 13-year period.
      RESULTS: The majority of accident causal factors were attributed to aircrew and
      the environment, with decidedly fewer associated with supervisory and
      organizational causes. Comparisons were made between HFACS causal categories and
      traditional situational variables such as visual conditions, injury severity, and
      regional differences. CONCLUSION: These data will provide support for the
      continuation, modification, and/or development of interventions aimed at
      commercial aviation safety. APPLICATION: HFACS provides a tool for assessing
      human factors associated with accidents and incidents.

PMID- 17447666
TI  - Errors in the heat of battle: taking a closer look at shared cognition breakdowns
      through teamwork.
AB  - OBJECTIVE: We developed a theoretically based taxonomy for classifying shared
      cognition breakdowns related to teamwork which contribute to fratricide
      incidents. BACKGROUND: Fratricide on the battlefield is an inescapable cost of
      war. A number of technological advancements have been made in terms of combat
      identification systems to reduce the risk of these incidents. However, fratricide
      continues to occur at alarming rates. METHOD: We take a human-centered approach
      to understanding errors leading to fratricide incidents by focusing on shared
      cognition. We turn to the literature and provide the theoretical foundations for
      an error classification taxonomy to improve understanding of why fratricide
      incidents occur. RESULTS: Based on our review of the literature, we identified a
      number of problem areas leading to fratricide incidents. However, many of the
      cited contributing factors were broad terms (e.g., poor coordination) and did
      little to tell us why the breakdown occurred and where improvements are needed.
      Therefore, we chose to focus on one specific area--teamwork breakdowns--and
      discuss in depth how these breakdowns contribute to fratricide. CONCLUSION: In
      this paper, we take a first step toward proposing a taxonomy that allows for the
      diagnostic assessment of what causes teamwork breakdowns in fratricide. We
      understand that a taxonomy is only as good as the data available and encourage
      richer case studies from which to learn. APPLICATION: To apply this taxonomy in
      an operational setting, we provide a set of behavioral markers that can be used
      to identify teamwork breakdowns on the battlefield.

PMID- 17447667
TI  - A review of medical error reporting system design considerations and a proposed
      cross-level systems research framework.
AB  - OBJECTIVE: To review the literature on medical error reporting systems, identify
      gaps in the literature, and present an integrative cross-level systems model of
      reporting to address the gaps and to serve as a framework for understanding and
      guiding reporting system design and research. BACKGROUND: Medical errors are
      thought to be a leading cause of death among adults in the United States.
      However, no review exists summarizing what is known about the barriers and
      facilitators for successful reporting systems, and no integrated model exists to
      guide further research into and development of medical error reporting systems.
      METHOD: Relevant literature was identified using online databases; references in
      relevant articles were searched for additional relevant articles. RESULTS: The
      literature review identified components of medical error reporting systems, error
      reporting system design choices, barriers and incentives for reporting, and
      suggestions for successful reporting system design. Little theory was found to
      guide the published research. An integrative cross-level model of medical error
      reporting system design was developed and is proposed as a framework for
      understanding the medical error reporting literature, addressing existing
      limitations, and guiding future design and research. CONCLUSION: The medical
      error reporting research provides some guidance for designing and implementing
      successful reporting systems. The proposed cross-level systems model provides a
      way to understand this existing research. However, additional research is needed
      on reporting and related safety actions. The proposed model provides a framework
      for such future research. APPLICATION: This work can be used to guide the design,
      implementation, and study of medical error reporting systems.

PMID- 17447668
TI  - Effect of workload history on task performance.
AB  - OBJECTIVE: This study investigated the effects of workload history (specifically,
      sudden shifts in workload) on performance. BACKGROUND: In 1993 the National
      Research Council identified workload transition as an important concern for human
      factors researchers. The study of workload history suggests that what an
      individual has been doing prior to a point in time has an effect on subsequent
      performance. One trend emerging from workload history studies is that a general
      decrement in performance is most likely to occur following a decrease in task
      demand. METHOD: The 198 participants were randomly assigned to a high-to-low or
      low-to-high condition. Participants performed a version of the Bakan Vigilance
      Task while correct responses, response times, and total errors were recorded.
      RESULTS: Results supported previous research suggesting a workload decrease
      results in a performance decrement. More importantly, this study reports that
      either a sudden increase or decrease could lead to a loss in accuracy and a
      slowing of response time in a longer time course. CONCLUSION: An explanation of
      the decrement is offered in terms of adaptation models. In addition, a follow-up
      study suggested that the decrement is a result of something inherent in the
      workload shift rather than an effect of fatigue. APPLICATION: Workload history
      (more specifically, a workload shift) has significant implications for many work
      environments. These implications are particularly salient in occupations where
      individuals are confronted with varying levels of workload demand, especially
      safety-sensitive occupations.

PMID- 17447669
TI  - Perceived and actual grasp forces on cylindrical handles.
AB  - OBJECTIVE: To compare the grasp force and the perceived grasp force, as a
      percentage of the maximum voluntary contraction (MVC), on cylindrical handles and
      describe a functional relationship between the two. BACKGROUND: Repeated forceful
      exertions during work are associated with musculoskeletal disorders, and direct
      measurement of those forces is often difficult. Estimates are frequently made
      based on the judgments of force relative to the maximum grasp force capability of
      the individual. METHOD: Participants exerted grasp forces on five sizes of
      cylindrical handles. Pressure values at 16 locations (12 on the fingers and 4 on
      the distal ends of the metacarpal bones) were measured. Participants were asked
      to exert what they perceived to be specific percentages (in 10% increments) of
      their maximum grasp force on each of the five handles. RESULTS: A linear
      relationship between perceived and actual grasp force was found up to the point
      of about 80% of perceived MVC. Above that point, the relationship became
      quadratic. A piecewise regression model was developed to fit the entire range of
      perceived grasp forces in one model. CONCLUSION: Grasp force is linear and
      consistent up until the perceived percentage MVC reaches 80%. After that point
      the relationship becomes quadratic. APPLICATION: In actual application, for grasp
      on cylindrical handles, practitioners can use a linear relationship between
      perceived percentage MVC and actual percentage MVC for perceived percentages of
      80% or less. Above 80%, the piecewise quadratic relationship should be used.

PMID- 17447670
TI  - What you don't know can hurt you: factors impacting diagnosis in the automated
      cockpit.
AB  - OBJECTIVE: We examined the impact of operational variables on diagnosis and
      decision-making processes, focusing on information search. BACKGROUND: Arguably,
      the "best" decision-making processes in high-technology cockpits would be those
      that are both correspondent (objectively accurate) and coherent (rationally
      sound). In the electronic world, coherence in terms of identification and
      incorporation of all relevant information is both a prerequisite to and a
      limiting factor for accurate diagnosis and decision making. METHOD: Regional
      carrier pilots (N=93) responded to six scenarios by accessing information to
      determine a diagnosis and decision. RESULTS: Time pressure, a common operational
      variable, had a strong negative effect on information search and diagnosis
      accuracy, and the presence of noncongruent information heightened these negative
      effects. Unexpectedly, source of initial information (automated or other) did not
      impact any of the dependent variables. Diagnosis confidence was unrelated to
      accuracy and was negatively related to amount of information accessed.
      CONCLUSION: Results confirm both the need for coherence in diagnostic processes
      and the difficulty of maintaining it under time pressure. APPLICATION: One
      implication of the results of this study is that pilots in high-technology
      cockpits must be trained to utilize coherent diagnostic processes as standard
      operating procedure. Additionally, because thorough information search for
      diagnosis in an automated environment is essential, automated systems must be
      designed to foster coherent, and thus accurate, diagnostic processes.

PMID- 17447671
TI  - Formal analysis and automatic generation of user interfaces: approach,
      methodology, and an algorithm.
AB  - OBJECTIVE: We present a formal approach and methodology for the analysis and
      generation of user interfaces, with special emphasis on human-automation
      interaction. BACKGROUND: A conceptual approach for modeling, analyzing, and
      verifying the information content of user interfaces is discussed. METHODS: The
      proposed methodology is based on two criteria: First, the interface must be
      correct--that is, given the interface indications and all related information
      (user manuals, training material, etc.), the user must be able to successfully
      perform the specified tasks. Second, the interface and related information must
      be succinct--that is, the amount of information (mode indications, mode buttons,
      parameter settings, etc.) presented to the user must be reduced (abstracted) to
      the minimum necessary. RESULTS: A step-by-step procedure for generating the
      information content of the interface that is both correct and succinct is
      presented and then explained and illustrated via two examples. CONCLUSIONS: Every
      user interface is an abstract description of the underlying system. The
      correspondence between the abstracted information presented to the user and the
      underlying behavior of a given machine can be analyzed and addressed formally.
      APPLICATIONS: The procedure for generating the information content of user
      interfaces can be automated, and a software tool for its implementation has been
      developed. Potential application areas include adaptive interface systems and
      customized/personalized interfaces.

PMID- 17447672
TI  - Designing for attention with sound: challenges and extensions to ecological
      interface design.
AB  - OBJECTIVE: We explore whether ecological interface design (EID) principles can be
      applied to the design of an auditory display for anesthesia monitoring.
      BACKGROUND: EID examples focus almost exclusively on visual displays. In the
      anesthesia work environment, however, auditory displays may provide better
      individual and team awareness of patient state. METHOD: Using a work domain
      analysis of physiological monitoring in anesthesia, we identify information to
      display. Using the skills, rules, and knowledge distinction we identify cognitive
      control needed. Using semantic mapping we map physiological variables and
      constraints to auditory dimensions. RESULTS: EID principles do not address when
      information should be displayed and to whom. An attentional mapping stage helps
      to specify answers to these questions so that a workable auditory display for
      anesthesia monitoring is achieved. CONCLUSION: EID principles of representing
      work domain functional structure and minimizing resource-demanding cognitive
      control are necessary but insufficient to specify requirements for an effective
      auditory display. Also needed are analyses of control tasks, strategies, and the
      social organization of work. Such analyses are an integral part of the broader
      cognitive work analysis framework from which EID emerged. APPLICATION: Actual or
      potential uses of this research include the design of displays that support
      continuous peripheral awareness in collaborative multimodal work environments.

PMID- 17447673
TI  - A couple of comments...

PMID- 17447674
TI  - Compliments to the author.

PMID- 17447676
TI  - To scoop or not to scoop.

PMID- 17447675
TI  - Blackboard basics for Lab 101.

PMID- 17447677
TI  - Use some horse sense with QC.
AB  - What do we need to do to improve Lab QC practice? Maybe it is time to take a
      lesson from the folks with horse sense. Recognize there is a problem. Look
      closely and critically at QC processes. Help each other improve by benchmarking
      performance against performance standards and sharing best practices. Begin to
      change practices and share stories to encourage others. When a mistake is made
      when training or riding a horse, repercussions are immediate and personal. But a
      mistake made in the design or application of quality control means the patient
      and physician suffer the pain.

PMID- 17447678
TI  - Lady Luck smiles on the salary jackpot.

PMID- 17447679
TI  - Obviate personnel-shortage problems using lab orientation to retain essential
      support staff.

PMID- 17447680
TI  - Clarify test-results dilemma.

PMID- 17447681
TI  - Providence Med Center lab is going to the dogs.

PMID- 17447682
TI  - A new solution may modify healthcare.

PMID- 17447683
TI  - We can improve primal health.

PMID- 17447684
TI  - Midwifery model of care--phase II: networks in the birth community.

PMID- 17447685
TI  - Marion's message. MDG 5: something we can work with.

PMID- 17447686
TI  - Primal health: history of a concept.

PMID- 17447687
TI  - Antisocial behaviours from a primal health research perspective.

PMID- 17447688
TI  - Trusting birth even more.

PMID- 17447689
TI  - Group B strep prophylaxis: what are we creating?

PMID- 17447690
TI  - Epidurals: risks and concerns for mother and baby.

PMID- 17447691
TI  - Nine Web site strategies to generate more clients.

PMID- 17447692
TI  - Who is the bully?

PMID- 17447693
TI  - Manual rotation maneuvers for persistent OP position.

PMID- 17447694
TI  - Psychological and emotional dystocia.

PMID- 17447695
TI  - Foreskins for keeps--an idea whose time has come. The end of circumcision by the
      first of January 2007 one woman's path to this project.

PMID- 17447696
TI  - A Lamentation of birth.

PMID- 17447697
TI  - The midwife's grandchild: when the new grandmother is an expert on babies and
      birth.

PMID- 17447698
TI  - The language of desire.

PMID- 17447699
TI  - The business of midwifery: the financial plan.

PMID- 17447700
TI  - The Dutch system of perinatal care.

PMID- 17447701
TI  - Philippines needs help from breastfeeding activists.

PMID- 17447702
TI  - My midwifery practice in Israel.

PMID- 17447703
TI  - Soaking in midwifery.

PMID- 17447704
TI  - Baby breath.

PMID- 17447705
TI  - Birth in Sweden.

PMID- 17447706
TI  - Snakes of medical importance in India: is the concept of the "Big 4" still
      relevant and useful?
AB  - Snakebites continue to be a major medical concern in India. However, there is
      very little hard evidence of a numerical nature to enable us to understand which
      species are responsible for mortality and morbidity. For many decades, the
      concept of the "Big 4" Snakes of Medical Importance has reflected the view that 4
      species are responsible for Indian snakebite mortality--the Indian cobra (Naja
      naja), the common krait (Bungarus caeruleus), the Russell's viper (Daboia
      russelii) and the saw-scaled viper (Echis carinatus). However, a recent discovery
      that another species, the hump-nosed pit viper (Hypnale hypnale), is capable of
      causing lethal envenomation, and that this problem was being concealed by
      systematic misidentification of this species as the saw-scaled viper, has
      necessitated a review of the concept of the "Big 4." The concept of the "Big 4"
      snakes is reviewed to demonstrate its failure to include all currently known
      snakes of medical significance in India, and its negative effects related to
      clinical management of snakebite. The emergence of the hump-nosed pit viper
      (Hypnale hypnale) as a snake of medical significance has rendered the "Big 4"
      obsolete in terms of completeness. The concept of the "Big 4" is restricting
      sound epidemiological work and the development of effective snake antivenoms. It
      should be replaced by the model introduced in the 1980s by the World Health
      Organization, which has not received adequate circulation and implementation.

PMID- 17447707
TI  - The perception of risk and risk taking behavior: implications for incident
      prevention strategies.
AB  - Core to incident prevention strategies is the need to identify factors that
      influence the decision-making process linked to risk-taking behavior.
      Participants' perception of risk and associated norms and practices may play a
      key role in relation to decisions to engage with a risk and subsequent risk
      management strategies. A range of factors that influence the perception of risk
      and risk-taking behavior are discussed. It is proposed that prevention strategies
      need to be sensitive to the context of participation, the attitudes and beliefs
      of participants, and the motives for participation. To ignore such issues may
      result in the development of inappropriate approaches to the management of risk
      that may be discredited, resisted, or negate reasons for participation.

PMID- 17447708
TI  - Injury patterns and first aid training among canyoneers.
AB  - OBJECTIVE: To identify injury patterns in canyoneering and develop a sense of
      their frequency. METHODS: A web-based survey of canyoneers was developed.
      Questions regarding injuries experienced or treated, first aid training, and
      first aid supplies carried were included. RESULTS: A total of 38 responses were
      received. Cutaneous injuries were very common (average 2 per person per year),
      but of apparently low morbidity (no evacuations required). Orthopedic injuries
      were also common (1 sprain/strain per person every 3 years on average, and major
      injuries happening to 1 in 2 canyoneers during their career), as were
      environmental injuries. First aid preparedness, in terms of training and kits,
      varied quite widely, but there was significant interest in further training.
      CONCLUSIONS: Minor cutaneous and orthopedic injuries are common, but fortunately
      do not often require outside assistance. More significant injuries are less
      common and usually involve orthopedic trauma or environmental exposure. A first
      aid curriculum for canyoneering should cover stabilization of fractures,
      analgesia and evacuation techniques as well as minor wound care.

PMID- 17447709
TI  - Injuries and illnesses of big game hunters in western Colorado: a 9-year
      analysis.
AB  - OBJECTIVE: The purpose of this study was to characterize big game hunter visits
      to a rural hospital's emergency department (ED). Using data collected on
      fatalities, injuries, and illnesses over a 9-year period, trends were noted and
      comparisons made to ED visits of alpine skiers, swimmers, and bicyclists. Out-of
      hospital hunter fatalities reported by the county coroner's office were also
      reviewed. Cautionary advice is offered for potential big game hunters and their
      health care providers. METHODS: Self-identified hunters were noted in the ED log
      of a rural Colorado hospital from 1997 to 2005, and injury or illness and outcome
      were recorded. Additional out-of-hospital mortality data were obtained from the
      county coroner's office. The estimated total number of big game hunters in the
      hospital's service area and their average days of hunting were reported by the
      Colorado Division of Wildlife. The frequencies of hunters' illnesses, injuries,
      and deaths were calculated. RESULTS: A total of 725 ED visits--an average of 80
      per year--were recorded. Nearly all visits were in the prime hunting months of
      September to November. Twenty-seven percent of the hunter ED patients were
      Colorado residents, and 73% were from out of state. Forty-five percent of the
      visits were for trauma, 31% for medical illnesses, and 24% were labeled "other."
      The most common medical visits (105) were for cardiac signs and symptoms, and all
      of the ED deaths (4) were attributed to cardiac causes. The most common trauma
      diagnosis was laceration (151), the majority (113) of which came from accidental
      knife injuries, usually while the hunter was field dressing big game animals.
      Gunshot wounds (4, < 1%) were rare. Horse-related injuries to hunters declined
      while motor vehicle- and all-terrain vehicle (ATV)-related injuries increased.
      The five out-of-hospital deaths were cardiac related (3), motor vehicle related
      (1), and firearm related (1). CONCLUSIONS: Fatal outcomes in big game hunters
      most commonly resulted from cardiac diseases. Gunshot injuries and mortalities
      were very low in this population. Knife injuries were common. Hunters and their
      health care providers should consider a thorough cardiac evaluation prior to big
      game hunts. Hunter safety instructors should consider teaching aspects of safe
      knife use. Consideration should be given to requiring and improving ATV driver
      education.

PMID- 17447710
TI  - Mountain sickness knowledge among foreign travelers in Cuzco, Peru.
AB  - OBJECTIVE: Cuzco, Peru, is host to a dangerous mix of high altitude and rapid
      access from low elevation, which results in a high prevalence of acute mountain
      sickness (AMS). Thus, it is important that travelers entering Cuzco understand
      the basics of AMS. To this end, we assessed travelers' awareness of AMS,
      especially the resources used to obtain this knowledge. With this information we
      make recommendations with regard to better avenues for distribution of AMS
      information. METHODS: One hundred foreign travelers, representing an
      international population, completed a 45-item written questionnaire that was
      subsequently analyzed. RESULTS: Over half of the respondents (51%) rated their
      knowledge of AMS as "low" or "none." Furthermore, very few respondents knew about
      acetazolamide (Diamox) as prophylaxis for (9%) or treatment of AMS (5%). People
      who consulted physicians for AMS information were more likely to know about the
      utility of acetazolamide than those who depended on a guidebook (P = .0266) but
      were less likely to correctly identify the symptomatology of AMS (P = .047).
      While AMS knowledge was poor, the majority of travelers (90%) indicated
      compliance with recommended pretravel vaccinations. CONCLUSIONS: This survey adds
      to the body of knowledge that indicates a lack of AMS knowledge among travelers.
      In addition, this survey identifies 2 potential avenues for improved dispersal of
      information: 1) guidebooks for countries of concern and 2) national health agency
      Web sites linked to information on pretravel vaccinations. Recommendations are
      made to utilize these commonly accessed resources to increase AMS information
      distribution to the general populous.

PMID- 17447711
TI  - Pattern of injury after rock-climbing falls is not determined by harness type.
AB  - OBJECTIVE: Experimental data indicate that when using a sit harness alone, any
      major fall during rock climbing may cause life-threatening thoraco-lumbar
      hyperextension trauma or "head down position" during suspension. To clarify the
      actual influence of the type of harness on the pattern and severity of injury,
      accidents involving a major fall in a climbing harness were analyzed
      retrospectively. METHODS: Individuals with a height of fall equal to or exceeding
      5 m were identified through a search of accident and emergency records for the
      period from 2000 to 2004. Data concerning the circumstances of the fall and the
      patterns of injury were obtained from personal interviews, flight and accident
      reports, as well as hospital medical records. RESULTS: Of a total of 113 climbers
      identified, 73 (64.6%) used a sit harness alone, whereas 40 (35.4%) used a body
      harness. Fractures and dislocations of the extremities, the shoulder, and the
      pelvic region were the most common injuries, while the most severe injuries
      occurred in the head and neck region. Although most falls were associated with
      mild or moderate injuries, 13 (11.5%) climbers sustained severe or critical
      multisystem trauma. Falls on more difficult routes were associated with less
      severe injury. The type of harness used did not influence the pattern or severity
      of injury. In particular, no evidence was found for the existence of a thoraco
      lumbar hyperextension trauma. CONCLUSIONS: The type of harness does not influence
      the pattern or severity of injury, and the forces transferred via the harness do
      not cause a specific harness-induced pathology. We did not find any evidence that
      hyperextension trauma of the thoraco-lumbar region is an important mechanism of
      injury in climbers using a sit harness alone. Rock contact during the fall, and
      not the force transferred through the harness, is the major cause of significant
      injury in climbing accidents.

PMID- 17447712
TI  - Injury and illness aboard an Antarctic cruise ship.
AB  - OBJECTIVE: The objective of this study was to determine the incidence and
      patterns of injury and illness among passengers aboard a cruise ship in
      Antarctica. METHODS: Demographic data on passengers were collected for all
      participants aboard Antarctica cruises on a single ship during the Antarctic
      summer cruise season of November 2004 through March 2005. Medical logs from each
      of 11 cruise trips were reviewed for presentation of injuries and illnesses.
      RESULTS: A total of 1057 passengers were included in the study, of which 47.4%
      were male. The mean age of the passengers was 54 years (+/- 16.5 years). The
      overall incidence rate of injury and illness was 21.7 per 1000 person-days.
      Motion sickness was the most common condition, comprising 42.3% of all medical
      encounters by the ship physician, followed by infectious diseases (17.2%) and
      injury (15.0%). The incidence rate of injury increased significantly with age,
      whereas the incidence rate of motion sickness decreased significantly with age.
      There was little variation in the incidence and patterns of injury and illness
      between genders. CONCLUSIONS: Most illnesses and injuries were due to the motion
      of the ship, and a large proportion of the passengers aboard the cruise ship in
      Antarctica were elderly. Injury among older passengers is of special concern.

PMID- 17447713
TI  - Human North American river otter (Lontra canadensis) attack.
AB  - As a result of the successful restoration and conservation programs deployed by
      state and federal agencies, populations of the North American river otter (Lontra
      canadensis) are increasing in many states. Recreational activities such as
      swimming, boating, and fishing increase the likelihood of human interactions with
      this charismatic, nonendangered mustelid. Otters tend to avoid areas of high
      human activity, occur at low population densities, and in some habitats in the
      United States have not recovered from population declines. Therefore,
      interactions with humans are rare, and aggressive encounters by otters are even
      less frequent. We report a recent, aggressive, and unprovoked attack that was
      followed by immediate medical treatment, including postexposure rabies
      prophylaxis, extensive suturing, and subsequent reconstructive surgery. We
      discuss river otter biology, the prevalence of diseases in wild populations of
      river otter, and otter attacks on humans and their treatment.

PMID- 17447714
TI  - High-altitude cerebral edema with absence of headache.
AB  - Headache is the cardinal symptom of acute mountain sickness (AMS). The headache
      normally worsens, with increased cerebral affection and the development of high
      altitude cerebral edema (HACE). A Norwegian expedition aimed to climb Baruntse
      (7129 m) in Nepal in 2003. At 5400 m a 35-year-old man felt exhausted. The next
      day he aborted his attempt at further climbing as a result of extreme fatigue.
      Over the next 24 hours he developed cough, dyspnea, and severe hypoxia before
      progressing to ataxia and blurred vision. At no point did he experience headache
      or nausea. The patient was evacuated by helicopter. He improved immediately after
      descent and recovered completely within a week. The speed of progression from AMS
      to HACE varies. Abrupt onset of HACE is occasionally reported. High-altitude
      pulmonary edema (HAPE) may induce severe hypoxia that can lead to rapid
      development of HACE. High-altitude cerebral edema in the setting of HAPE was the
      most likely diagnosis despite the unusual lack of headache. Rapid onset of HAPE
      with subsequent severe desaturation should raise awareness of the development of
      HACE, even in the absence of headache.

PMID- 17447715
TI  - Hematocrit change in tropical scuba divers.
AB  - OBJECTIVE: Direct evidence that dehydration results from scuba diving is scanty.
      Increased hematocrit (Ht) is a commonly used proxy measure for dehydration. This
      study sought evidence that an increase in Ht occurs over the course of a scuba
      dive in tropical conditions. As a secondary outcome, evidence was sought that the
      degree of Ht increase is correlated to pressure exposure. METHODS: Twenty male
      and 21 female scuba divers were recruited at a remote tropical dive site. Water
      temperature was 30 degrees C (+/- 1 degrees C). Each diver gave venous blood
      relating to 1 dive only. Mean maximum dive depth was 13.6 m (+/- 3.7 m [SD]) and
      mean duration 39.5 minutes (+/- 4.5 minutes [SD]) using air as the breathing gas.
      Blood was taken at a mean of 12.4 minutes (+/- 3.5 minutes [SD]) before diving
      and a mean of 16.2 minutes (+/- 3.7 minutes [SD]) after diving. After
      centrifugation of microcapillaries, Ht was estimated on a visual plate reader.
      RESULTS: A paired Wilcoxon test showed evidence (P < .001) for a change in Ht.
      The mean difference between predive and postdive measurements was 0.0073 (95%
      confidence interval: 0.0104-0.0042), equating to a mean relative Ht increase of
      1.78%. Similar results were found for the sexes individually. A correlation
      between maximum depth of dive and Ht increase was statistically significant,
      although the correlation itself was weak (P = .049, Spearman's r = .326).
      CONCLUSIONS: There is evidence of a statistically significant increase in Ht over
      the course of a single warm-water scuba dive. This increase is small and is
      within the range of error associated with the techniques of Ht estimation
      employed in this study. Depth exposure was found to correlate with Ht increase.
      In view of the small magnitude of change in the Ht, there is no reason to amend
      protocols for fluid resuscitation of recreational scuba divers suspected to have
      experienced decompression injury in tropical locations.

PMID- 17447716
TI  - Research at the extremes: lessons from the 1981 American Medical Research
      Expedition to Mt Everest.

PMID- 17447717
TI  - Motor vehicle vs deer: an antler injury to the ring finger.

PMID- 17447718
TI  - Wild flowers and mad honey.

PMID- 17447719
TI  - High-altitude pulmonary edema getting worse after descent? An unlikely event.

PMID- 17447720
TI  - Prevention of acute mountain sickness in Nepali porters: a controlled trial.

PMID- 17447722
TI  - The structure and function of Saccharomyces cerevisiae proteinase A.
AB  - Saccharomyces cerevisiae proteinase A (saccharopepsin; EC 3.4.23.25) is a member
      of the aspartic proteinase superfamily (InterPro IPR001969), which are
      proteolytic enzymes distributed among a variety of organisms. Targeted to the
      vacuole as a zymogen, its activation at acidic pH can occur by two different
      pathways, a one-step process to release mature proteinase A, involving the
      intervention of proteinase B, or a step-wise pathway via the autoactivation
      product known as pseudo-proteinase A. Once active, S. cerevisiae proteinase A is
      essential to the activities of other yeast vacuolar hydrolases, including
      proteinase B and carboxypeptidase Y. The mature enzyme is bilobal, with each lobe
      providing one of the two catalytically essential aspartic acid residues in the
      active site. The crystal structure of free proteinase A reveals that the flap
      loop assumes an atypical position, pointing directly into the S(1) pocket of the
      enzyme. With regard to hydrolysis, proteinase A has a preference for hydrophobic
      residues with Phe, Leu or Glu at the P1 position and Phe, Ile, Leu or Ala at P1',
      and is inhibited by IA(3), a natural and highly specific inhibitor produced by S.
      cerevisiae. This review is the first comprehensive review of S. cerevisiae PrA.

PMID- 17447723
TI  - Differences in telomerase expression by the CD1a+ cells in Langerhans cell
      histiocytosis reflect the diverse clinical presentation of the disease.
AB  - Langerhans cell histiocytosis (LCH) is a disease characterized by an uncontrolled
      clonal proliferation of Langerhans cells, whose aetiology is still unclear. The
      clonal nature of LCH could support the hypothesis that it is a neoplastic disease
      with unlimited growth potential. One requirement for unlimited proliferation is
      the maintenance of telomere length. In a group of 70 patients, we set out to
      investigate whether a telomere maintenance mechanism is indeed active in LCH
      cells. This work showed that LCH cells from all restricted skin LCH lesions (6/6)
      expressed telomerase as assessed by human telomere reverse transcriptase (hTERT)
      immunohistochemistry, whereas LCH cells from the majority of the bone lesions
      analysed did not express hTERT (26/34). Interestingly, in contrast to the
      solitary bone lesions, LCH cells from lesions of multi-system patients always
      expressed telomerase (11/11), regardless of the lesional site. In situ telomeric
      repeat amplification protocol (TRAP) assays performed on different lesional sites
      showed that this telomerase was active. In addition, the telomere length of LCH
      cells from a hTERT-positive skin multi-system lesion was long and homogeneous
      when compared to that in the LCH cells from hTERT-negative bone single-system LCH
      lesions, which was heterogeneous in length. No evidence for an alternative
      lengthening of telomeres mechanism was found in hTERT-negative lesions. The
      difference in telomerase expression and telomere length at the different lesional
      sites and in biopsies from patients with solitary versus multi-system disease
      appears to reflect the diverse clinical presentation and course of this disease.
      The results from this study have important implications for understanding the
      nature of this disease.

PMID- 17447724
TI  - Using luminescent nanoparticles as staining probes for Affymetrix GeneChips.
AB  - Microarray technology provides efficient access to genetic information using
      miniaturized, high-density arrays of DNA probes. We investigated the application
      of luminescent nanoparticles as probes for Affymetrix GeneChips detection without
      the need for signal amplification. Our goal is to investigate the feasibility of
      using luminescent nanoparticles as probes in a commercial microarray system
      without changing its configurations. With the present imaging modality and
      existing optical excitation and detection systems of the Affymetrix GeneChips,
      our early results indicate that nanoparticles not only can be used for GeneChip
      labeling but also are superior to the traditional fluorescent protein
      streptavidin-phycoerythrin (SAPE). The advantage of the particles lies in a
      simplified staining procedure, higher photobleaching threshold, and enhanced
      luminescence signal. The nanoparticles can be used for detection of low-abundance
      targets without any amplification step. A concentration detection limit of 50 fM
      has been achieved. This work demonstrates the feasibility of using luminescent
      nanoparticles as probes for commercial microarray systems, making them less
      costly, more reproducible, and potentially quantitative.

PMID- 17447725
TI  - Expression vectors for enzyme restriction- and ligation-independent cloning for
      producing recombinant His-fusion proteins.
AB  - In this work we have constructed two novel expression vectors, designated as
      pURI2 and pURI3, which enable parallel cloning of a given target gene for
      producing recombinant His-fusion proteins. The vectors were created using the
      well-known pT7-7 and pIN-III-A3 plasmids as their template. The same DNA fragment
      containing the His-tag, enterokinase cleavage site, and a NotI unique site, as
      well as keeping the HindIII unique restriction site, was introduced in both
      vectors. These vectors have been designed to avoid the enzyme restriction and
      ligation steps during the cloning. The unique NotI site was introduced to
      facilitate the selection of the adequate recombinant plasmid. Parallel cloning of
      the same polymerase chain reaction fragment can be carried out since both vectors
      shared the same leader sequence. The described strategy avoids tedious cloning
      efforts into different expression vectors and represents a highly efficient means
      of cloning. To validate our vectors, we have cloned one target gene in both
      vectors and used expression and purification techniques to obtain the recombinant
      target protein. We herein show that both vectors function effectively in all the
      required experimental steps-cloning, expression, purification, and cleavage.

PMID- 17447726
TI  - Numerical fluorescence correlation spectroscopy for the analysis of molecular
      dynamics under nonstandard conditions.
AB  - The suitability of mathematical models used to extract kinetic information from
      correlated data constitutes a significant issue in fluorescence correlation
      spectroscopy (FCS). Standard FCS equations are derived from a simple Gaussian
      approximation of the optical detection volume, but some investigations have
      suggested this traditional practice can lead to inaccurate and misleading
      conclusions under many experimental circumstances, particularly those encountered
      in one-photon confocal measurements. Furthermore, analytical models cannot be
      derived for all measurement scenarios. We describe a novel numerical approach to
      FCS that circumvents conventional analytical models, enabling meaningful analyses
      even under extraordinarily unusual measurement conditions. Numerical fluorescence
      correlation spectroscopy (NFCS) involves quantitatively matching experimental
      correlation curves with synthetic curves generated via diffusion simulation or
      direct calculation based on an experimentally determined 3D map of the detection
      volume. Model parameters are adjusted iteratively to minimize the residual
      differences between synthetic and experimental correlation curves. In order to
      reduce analysis time, we distribute calculations across a network of processors.
      As an example of this new approach, we demonstrate that synthetic autocorrelation
      curves correspond well with experimental data and that NFCS diffusion
      measurements of Rhodamine B remain constant, regardless of the distortion present
      in a confocal detection volume.

PMID- 17447727
TI  - Naked-eye cadmium sensor: using chromoionophore arrays of Langmuir-Blodgett
      molecular assemblies.
AB  - This study demonstrates the possibility of a reversible naked-eye detection
      method for submicromolar levels of cadmium(II) using the Langmuir-Blodgett (L-B)
      technique. Molecular assemblies of 4-n-dodecyl-6-(2-thiazolylazo)resorcinol are
      transferred on precleaned microscopic glass slides, to act as a sensing probe.
      Isotherm (pi-A) measurements were performed to ensure the films' structural
      rigidity and homogeneity during sensor fabrication. The sensor surface morphology
      was characterized using atomic force microscopy and scanning electron microscopy.
      The probe membrane exhibits visual color transition, forming a series of reddish
      orange to pinkish-purple complexes with cadmium, over a wide concentration range
      (0.04-44.5 microM). Cadmium response kinetics and the changes in the sensors'
      intrinsic optical properties were monitored using absorption spectroscopy and
      further confirmed using X-ray photoelectron spectroscopy. A hybrid L-B film
      composite of poly(vinyl stearate) and poly(vinyl-N-octadecylcarbamate) were
      investigated for enhancing sensor performance. The sensor was tested for its
      practical approach to prove its cadmium selectivity and sensitivity amid common
      matrix constituents using synthetic mixtures and real water samples. Using the
      sensor strips, the respective lower limits of cadmium detection and
      quantification are 0.039 and 0.050 microM, as estimated from a normalized linear
      calibration plot.

PMID- 17447728
TI  - On-chip surface-based detection with nanohole arrays.
AB  - A microfluidic device with integrated surface plasmon resonance (SPR) chemical
      and biological sensors based on arrays of nanoholes in gold films is
      demonstrated. Widespread use of SPR for surface analysis in laboratories has not
      translated to microfluidic analytical chip platforms, in part due to challenges
      associated with scaling down the optics and the surface area required for common
      reflection mode operation. The resonant enhancement of light transmission through
      subwavelength apertures in a metallic film suggests the use of nanohole arrays as
      miniaturized SPR-based sensing elements. The device presented here takes
      advantage of the unique properties of nanohole arrays: surface-based sensitivity;
      transmission mode operation; a relatively small footprint; and repeatability.
      Proof-of-concept measurements performed on-chip indicated a response to small
      changes in refractive index at the array surfaces. A sensitivity of 333 nm per
      refractive index unit was demonstrated with the integrated device. The device was
      also applied to detect spatial microfluidic concentration gradients and to
      monitor a biochemical affinity process involving the biotin-streptavidin system.
      Results indicate the efficacy of nanohole arrays as surface plasmon-based sensing
      elements in a microfluidic platform, adding unique surface-sensitive diagnostic
      capabilities to the existing suite of microfluidic-based analytical tools.

PMID- 17447729
TI  - Strategic use of immunoprecipitation and LC/MS/MS for trace-level protein
      quantification: myosin light chain 1, a biomarker of cardiac necrosis.
AB  - Myosin light chain 1 (Myl3) is a 23-kDa isoform of one of the subunits of myosin,
      a protein involved in muscle contraction. Myl3 is presently being studied as a
      biomarker of cardiac necrosis to predict drug-induced cardiotoxicity, and in the
      work presented here, an LC/MS/MS assay was developed and validated to measure
      Myl3 in rat serum. The key steps in this approach involved immunoaffinity
      purification of Myl3 from serum followed by on-bead digestion with trypsin to
      release a surrogate peptide. This tryptic peptide was quantified using a
      synthetic peptide standard and a corresponding stable isotope-labeled internal
      standard, and the results were stoichiometrically converted to Myl3 serum
      concentrations. Myl3 concentrations were corrected for peptide recovery following
      immunoprecipitation and digestion (85%) and showed excellent agreement with
      synthetic peptide standards. Both the synthetic peptide and His-Myl3 protein were
      used to evaluate assay accuracy (% RE) and precision (% CV), which were measured
      on each of 3 days. The synthetic peptide was evaluated over the range of 0.073
      7.16 nM, while Myl3 protein QC samples prepared in rat serum were evaluated over
      the range of 0.13-6.62 nM. To prepare control matrix, endogenous Myl3 was
      immunodepleted from pooled rat serum. Peptide interday accuracy and precision did
      not exceed 7.6 and 11.1%, and Myl3 interday accuracy and precision did not exceed
      12.9 and 13.2%, respectively. Data are presented from the application of this
      assay to establish a time course in which rats demonstrated a marked increase in
      Myl3 serum concentrations following administration of isoproterenol, a beta
      adrenergic receptor agonist known to induce cardiac injury. This assay is an
      example of a larger effort in our laboratory to use LC/MS/MS in conjunction with
      immunoaffinity techniques to evaluate candidate biomarkers of target organ
      toxicity and to expedite the development of biomarker assays for drug
      development.

PMID- 17447730
TI  - Simplifying CE-MS operation. 2. Interfacing low-flow separation techniques to
      mass spectrometry using a porous tip.
AB  - A robust, reproducible, and single-step interface design between low flow rate
      separation techniques, such as sheathless capillary electrophoresis (CE) and
      nanoliquid chromatography (nLC), and mass spectrometry (MS) using electrospray
      ionization (ESI), is introduced. In this design, the electrical connection to the
      capillary outlet was achieved through a porous tip at the capillary outlet. The
      porous section was created by removing 1-1.5 in. of the polyimide coating of the
      capillary and etching this section by 49% solution of HF until it is porous. The
      electrical connection to the capillary outlet is achieved simply by inserting the
      capillary outlet containing the porous tip into the existing ESI needle (metal
      sheath) and filling the needle with the background electrolyte. Redox reactions
      of water at the ESI needle and transport of these small ions through the porous
      tip into the capillary provides the electrical connection for the ESI and for the
      CE outlet electrode. The etching process reduces the wall thickness of the etched
      section, including the tip of the capillary, to 5-10 microm, which for a 20-30
      microm i.d. capillary results in stable electrospray at approximately 1.5 kV. The
      design is suitable for interfacing a wide range of capillary sizes with a wide
      range of flow rates to MS via ESI, but it is especially useful for interfacing
      narrow (<30 microm i.d.) capillaries and low flow rates (<100 nL/min). The
      advantages of the porous tip design include the following: (1) its fabrication is
      reproducible, can be automated, and does not require any mechanical tools. (2)
      The etching process reduces the tip outer diameter and makes the capillary porous
      in one step. (3) The interface can be used for both nLC-MS and CE-MS. (4) If
      blocked or damaged, a small section of the tip can be etched off without any loss
      of performance. (5) The interface design leaves the capillary inner wall intact
      and, therefore, does not add any dead volume to the CE-MS or nLC-MS interface.
      (6) Bubble formation due to redox reactions of water at the high-voltage
      electrode is outside of the separation capillary and does not affect separation
      or MS performances. The performance of this interface is demonstrated by the
      analyses of amino acids, peptide, and protein mixtures.

PMID- 17447731
TI  - The carboxy-terminal region of apoA-I is required for the ABCA1-dependent
      formation of alpha-HDL but not prebeta-HDL particles in vivo.
AB  - ATP-binding cassette transporter A-1 (ABCA1)-mediated lipid efflux to lipid-poor
      apolipoprotein A-I (apoA-I) results in the gradual lipidation of apoA-I. This
      leads to the formation of discoidal high-density lipoproteins (HDL), which are
      subsequently converted to spherical HDL by the action of lecithin:cholesterol
      acyltransferase (LCAT). We have investigated the effect of point mutations and
      deletions in the carboxy-terminal region of apoA-I on the biogenesis of HDL using
      adenovirus-mediated gene transfer in apoA-I-deficient mice. It was found that the
      plasma HDL levels were greatly reduced in mice expressing the carboxy-terminal
      deletion mutants apoA-I[Delta(185-243)] and apoA-I[Delta(220-243)], shown
      previously to diminish the ABCA1-mediated lipid efflux. The HDL levels were
      normal in mice expressing the WT apoA-I, the apoA-I[Delta(232-243)] deletion
      mutant, or the apoA-I[E191A/H193A/K195A] point mutant, which promote normal ABCA1
      mediated lipid efflux. Electron microscopy and two-dimensional gel
      electrophoresis showed that the apoA-I[Delta(185-243)] and apoA-I[Delta(220-243)]
      mutants formed mainly prebeta-HDL particles and few spherical particles enriched
      in apoE, while WT apoA-I, apoA-I[Delta(232-243)], and apoA-I[E191A/H193A/K195A]
      formed spherical alpha-HDL particles. The findings establish that (a) deletions
      that eliminate the 220-231 region of apoA-I prevent the synthesis of alpha-HDL
      but allow the synthesis of prebeta-HDL particles in vivo, (b) the amino-terminal
      segment 1-184 of apoA-I can promote synthesis of prebeta-HDL-type particles in an
      ABCA1-independent process, and (c) the charged residues in the 191-195 region of
      apoA-I do not influence the biogenesis of HDL.

PMID- 17447733
TI  - Calculation of entropy and heat capacity of organic compounds in the gas phase.
      Evaluation of a consistent method without adjustable parameters. Applications to
      hydrocarbons.
AB  - The purpose of this study has been to determine how well a consistent ab initio
      thermostatistical method reproduces experimental values of heat capacity and
      entropy. The method has been applied to calculation of heat capacity and entropy
      of a representative set of hydrocarbons that includes compounds consisting of
      multiple conformers. All Cp and S values are for the gaseous state at 1 atm;
      units are cal K-1 mol-1. A detailed sensitivity (error) analysis has been
      performed to determine the root mean square (rms) values of errors expected of
      the calculated values: these are 0.27 cal for Cp and 0.36 cal for entropy. In
      comparing calculated values with experimental values, it is necessary to consider
      also the uncertainties of the experimental data. When these are included, the
      expected rms values of Cp(experimental) - Cp(calculated) values at 298.15 K range
      from 0.21 to 0.73. For S(experimental) - S(calculated), they range from 0.36 to
      0.72. Calculations with frequencies derived with the 6-31G(d,p) basis set and
      scaled by 0.91 yielded rms values for Cp(experimental) - Cp(calculated) of
      individual compounds from 0.14 to 0.84 cal and rms values for S(experimental) -
      S(calculated) of individual compounds from 0.07 to 1.11 cal. Calculated Cp values
      for 7 out of 16 compounds agree with experimental values within the rms
      uncertainty estimated for the compound, and 11 fall within twice that estimate.
      For entropy, the calculated values for 13 of 18 compounds agree with the very
      limited available experimental data within the rms estimated uncertainty for the
      compound, and 16 of 18 fall within twice the uncertainty.

PMID- 17447732
TI  - Comparative kinetics of cofactor association and dissociation for the human and
      trypanosomal S-adenosylhomocysteine hydrolases. 1. Basic features of the
      association and dissociation processes.
AB  - The S-adenosyl-l-homocysteine (AdoHcy) hydrolases catalyze the reversible
      conversion of AdoHcy to adenosine and homocysteine, making use of a catalytic
      cycle in which a tightly bound NAD+ oxidizes the 3-hydroxyl group of the
      substrate at the beginning of the cycle, activating the 4-CH bond for elimination
      of homocysteine, followed by Michael addition of water to the resulting
      intermediate and a final reduction by the tightly bound NADH to give adenosine.
      The equilibrium and kinetic properties of the association and dissociation of the
      cofactor NAD+ from the enzymes of Homo sapiens (Hs-SAHH) and Trypanosoma cruzi
      (Tc-SAHH) are qualitatively similar but quantitatively distinct. Both enzymes
      bind NAD+ in a complex scheme. The four active sites of the homotetrameric
      apoenzyme appear to divide into two numerically equal classes of active sites.
      One class of sites binds cofactor weakly and generates full activity very rapidly
      (in less than 1 min). The other class binds cofactor more strongly but generates
      activity only slowly (>30 min). In the case of Tc-SAHH, the final affinity for
      NAD+ is roughly micromolar and this affinity persists as the equilibrium
      affinity. In the case of Hs-SAHH, the slow-binding phase terminates in micromolar
      affinity also, but over a period of hours, the dissociation rate constant
      decreases until the final equilibrium affinity is in the nanomolar range. The
      slow binding of NAD+ by both enzymes exhibits saturation kinetics with respect to
      the cofactor concentration; however, binding to Hs-SAHH has a maximum rate
      constant around 0.06 s-1, while the rate constant for binding to Tc-SAHH levels
      out at 0.006 s-1. In contrast to the complex kinetics of association, both
      enzymes undergo dissociation of NAD+ from all four sites in a single first-order
      reaction. The equilibrium affinities of both Hs-SAHH and Tc-SAHH for NADH are in
      the nanomolar range. The dissociation rate constants and the slow-binding
      association rate constants for NAD+ show a complex temperature dependence with
      both enzymes; however, the cofactor always dissociates more rapidly from Tc-SAHH
      than from Hs-SAHH, the ratio being around 80-fold at 37 degrees C, and the
      cofactor binds more rapidly to Hs-SAHH than to Tc-SAHH above approximately 16
      degrees C. These features present an opening for selective inhibition of Tc-SAHH
      over Hs-SAHH, demonstrated with the thioamide analogues of NAD+ and NADH. Both
      analogues bind to Hs-SAHH with approximately 40 nM affinities but much more
      weakly to Tc-SAHH (0.6-15 microM). Nevertheless, both analogues inactivated Tc
      SAHH 60% (NAD+ analogue) or 100% (NADH analogue) within 30 min, while the degree
      of inhibition of Hs-SAHH approached 30% only after 12 h. The rate of loss of
      activity is equal to the rate of dissociation of the cofactor and thus 80-fold
      faster at 37 degrees C for Tc-SAHH.

PMID- 17447734
TI  - Experimental study and detailed modeling of toluene degradation in a low-pressure
      stoichiometric premixed CH4/O2/N2 flame.
AB  - Temperature and mole fraction profiles have been measured in laminar
      stoichiometric premixed CH4/O2/N2 and CH4/1.5%C6H5CH3/O2/N2 flames at low
      pressure (0.0519 bar) by using thermocouple, molecular beam/mass spectrometry
      (MB/MS), and gas chromatography/mass spectrometry (GC/MS) techniques. The present
      study completes our previous work performed on the thermal degradation of benzene
      in CH4/O2/N2 operating at similar conditions. Mole fraction profiles of
      reactants, final products, and reactive and stable intermediate species have been
      analyzed. The main intermediate aromatic species analyzed in the methane-toluene
      flame were benzene, phenol, ethylbenzene, benzylalcohol, styrene, and
      benzaldehyde. These new experimental results have been modeled with our previous
      model including submechanisms for aromatics (benzene up to p-xylene) and
      aliphatic (C1 up to C7) oxidation. Good agreement has been observed for the main
      species analyzed. The main reaction paths governing the degradation of toluene in
      the methane flame were identified, and it occurs mainly via the formation of
      benzene (C6H5CH3 + H = C6H6 + CH3) and benzyl radical (C6H5CH3 + H = C6H5CH2 +
      H2). Due to the abundance of methyl radicals, it was observed that recombination
      of benzyl and methyl is responsible for main monosubstitute aromatic species
      analyzed in the methane-toluene flame. The oxidation of these substitute species
      led to cyclopentadienyl radical as observed in a methane-benzene flame.

PMID- 17447735
TI  - Structures and electronic properties of Al7x0,- and Al13 X1,2,12- clusters with
      X=F, Cl, and Br.
AB  - The structures, binding energies, and electronic properties for Al7X, Al7X-,
      Al13X-, Al13X2-, and Al13X12- (X = F, Cl, Br) were studied at the B3LYP/6
      311+G(2d,p) level. Among the systems studied, Al7 and Al13 clusters in Al7X and
      Al13X- reveal alkali-like and halogen-like superatom characters, respectively.
      Al7 can bind with one halogen atom to form a salt-like compound as Al7+delta-X
      delta. Al13- can combine with one halogen atom to form a diatomic halogen anion
      Al13X-. However, when adding more halogens, the superatom structure would be
      destroyed, resulting in low-symmetry compounds with the center Al atom moving
      toward the cluster surface. The structures of Al13X1,2,12- (X = F, Cl, Br) are
      similar to those of X = I; however, their binding energies and electron
      structures are much different. In addition, the analyses of the calculated NBO
      charges show that Cl and Br have similar properties, but much different from F,
      when interacting with the Al clusters. The Al-Cl and Al-Br bonds have more
      covalent character in Al7X and Al13X2,12-, in contrast to the corresponding Al-F
      bond, which has prominent ionic character.

PMID- 17447736
TI  - Synthesis and magnetic properties of one-dimensional zinc nickel oxide solid
      solution.
AB  - A novel facile method has been demonstrated for large-scale synthesis of zinc
      oxide-based one-dimensional solid solution with a series percentage of nickel
      dopant. The obtained Zn1-xNixO nanorods were characterized by X-ray diffraction,
      transmission electron microscopy, selected area electron diffraction, and energy
      dispersed X-ray spectroscopy. The result shows that the obtained Zn1-xNixO
      nanorods are single crystalline with the Ni2+ dopants occupying tetrahedral Zn2+
      cation sites of wurtzite ZnO. Moreover, the Zn1-xNixO nanorods exhibit robust
      high-Curie-temperature (TC) ferromagnetism at 300 K.

PMID- 17447737
TI  - Structure of the naphthalene dimer from rare gas tagging.
AB  - Excitation spectra of naphthalene dimer-argonn (n = 1-3) clusters are obtained by
      resonance enhanced multiphoton ionization time-of-flight mass spectroscopy. The
      spectra are generally independent of the number of attached argon atoms and
      reveal sharp structures which are fitted by superimposing independent monomer
      spectra. It is concluded that the rare-gas tagging technique reveals the presence
      of a T-shaped naphthalene dimer chromophore in the molecular beam.

PMID- 17447738
TI  - Adsorption configurations and energetics of BClx (x=0-3) on TiO2 anatase (101)
      and rutile (110) surfaces.
AB  - This study investigates the adsorption and reactions of boron trichloride and its
      fragments (BClx) on the TiO2 anatase (101) and rutile (110) surfaces by first
      principles calculations. The results show that the possible absorbates on the
      TiO2 anatase and rutile surfaces are very similar. The single- and double-site
      adsorption configurations are found for both anatase and rutile surfaces. The
      particular adsorbate feature on the anatase surface is its in-plane double-site
      adsorption by Ti and O from its sawtooth surface. The potential energy surface
      shows that BCl3 can be adsorbed on the O site for both the anantase and rutile
      surfaces and the most of the BClx reaction on both anatase and rutile surfaces
      are endothermic, except for the dissociative reaction on the rutile surface. The
      energy levels of the BClx reactions between the anatase and rutile surfaces show
      that the rutile surface has lower energy levels than those of anatase surface.
      This result reveals that the BClx dissociative adsorption more easily occurs on
      rutile surface than on anatase surface.

PMID- 17447739
TI  - Photodissociation dynamics of the chromophores of the amino acid tyrosine: p
      methylphenol, p-ethylphenol, and p-(2-aminoethyl)phenol.
AB  - The photodissociation of p-methylphenol, p-ethylphenol, and p-(2
      aminoethyl)phenol, chromophores of the amino acid tyrosine, was studied
      separately for each compound in a molecular beam at 248 nm using multimass ion
      imaging techniques. They show interesting side-chain size-dependent dissociation
      properties. Only one dissociation channel, that is, H atom elimination, was
      observed for both p-methylphenol and p-ethylphenol. The photofragment
      translational energy distributions and potential energy surfaces from ab initio
      calculation suggest that H atom elimination occurs from a repulsive excited
      state. On the other hand, the H atom elimination channel is quenched completely
      by internal conversion and/or intersystem crossing in p-(2-aminoethyl)phenol.
      Only C-C bond cleavage was observed from p-(2-aminoethyl)phenol. The
      photofragment translational energy distribution shows a slow component and a fast
      component. The fast component results from dissociation on an electronic excited
      state, but the slow component occurs only after the internal conversion to the
      ground electronic state. Comparison with the photodissociation of phenol and
      ethylbenzene is made.

PMID- 17447740
TI  - Statistical thermodynamic description of homogeneous dispersive kinetics.
AB  - A statistical thermodynamic interpretation of homogeneous dispersive kinetics
      (which assumes the existence of a pseudo-equilibrium between a distribution of
      reagent states and a single activated state, which together define the rate
      determining step), coupled with a previous "quantum kinetic" description for this
      same type of system (Skrdla, P. J. J. Phys. Chem. A 2006, 110, 11494), is found
      to provide new insights into the kinetics of these conversions. In particular,
      the change in the (apparent) activation energy with conversion time is shown to
      be a function of the entropy change associated with the ensemble of reagent
      molecules as they traverse the activation energy barrier. Using these two
      "orthogonal" stochastic interpretations of dispersive kinetics, a fundamental
      physical description of the rate parameter beta in the author's model is
      obtained.

PMID- 17447741
TI  - Photoelectron imaging of atomic iodine following A-band photolysis of CH3I.
AB  - Photoionization of the iodine atom following methyl iodide A-band
      photodissociation was studied over the wavelength range of 245.5-261.6 nm by
      photoelectron imaging technique. Final state-specific speed and angular
      distributions of the photoelectron were recorded. Two types of the photoelectron
      resulted from ionizing the I atom from the photodissociation of CH3I were
      identified: (a) (2+1) REMPI of the ground state I atom, and (b) two-photon
      excitation of spin-orbit excited I(2P1/2) to autoionizing resonances converging
      to the 3P1 state of I+. In addition, some weaker signals were attributed to one
      photon ionization of I atoms produced in some higher excited states from
      multiphoton ionization of CH3I followed by dissociation. Analysis of relative
      branching ratios to different levels of I+ (in case a) revealed that the final
      ion level distributions are generally dominated by the preservation of the ion
      core configuration of the intermediate resonant state. A qualitative
      interpretation of the electron angular distribution from an autoionization
      process is also given.

PMID- 17447742
TI  - Interaction of amino acids with gold and silver clusters.
AB  - Binding of gold and silver clusters with amino acids (glycine and cysteine) was
      studied using density functional theory (DFT). Geometries of neutral, anionic,
      and cationic amino acids with Au3 and Ag3 clusters were optimized using the DFT
      B3LYP approach. The mixed basis set used here was denoted by 6-31+G** (union or
      logical sum)LANL2DZ. This work demonstrated that the interaction of amino acids
      with gold and silver clusters is governed by two major bonding factors: (a) the
      anchoring N-Au(Ag), O-Au(Ag), and S-Au(Ag) bonds and (b) the nonconventional N
      H...Au(Ag) and O-H...Au(Ag) hydrogen bonds. Among the three forms of amino acids,
      anionic ones exhibited the most tendency to interact with the Au and Ag clusters.
      Natural bond orbital analysis was performed to calculate charge transfer, natural
      population analysis, and Wiberg bond indices of the complexes. Atoms-in-molecules
      theory was also applied to determine the nature of interactions. It was shown
      that these bonds are partially electrostatic and partially covalent.

PMID- 17447743
TI  - Aromaticity of distorted benzene rings: exploring the validity of different
      indicators of aromaticity.
AB  - The effect of three in-plane (bond length alternation, bond length elongation,
      and clamping) and three out-of-plane deformations (boatlike, chairlike, and
      pyramidalization) on the aromaticity of the benzene molecule has been analyzed
      employing seven widely used indicators of aromaticity. It is shown that only the
      aromatic fluctuation index (FLU) is able to indicate the expected loss of
      aromaticity because of distortion from the equilibrium geometry in all
      deformations analyzed. As FLU has been shown previously to fail in other
      particular situations, we conclude that there is not yet a single indicator of
      aromaticity that works properly for all cases. Therefore, to reach safer
      conclusions, aromaticity analyses should be carried out employing a set of
      aromaticity descriptors on the basis of different physical manifestations of
      aromaticity.

PMID- 17447744
TI  - Fluorescence studies of terrylene in a supersonic jet: indication of a dark
      electronic state below the allowed transition.
AB  - Jet-cooled terrylene has been studied in helium buffer gas using a pulsed nozzle
      by means of laser-induced fluorescence. Fluorescence excitation and two-color
      depletion experiments (resulting in hole burning spectra) are presented. Analysis
      of the spectra leads to the conclusion that another excited electronic state is
      present in the vicinity of the allowed 1B1u state. Assuming (according to
      previous literature suggestions Karabunarliev, S.; Baumgarten, M.; Mullen, K. J.
      Phys. Chem. A 1998, 102, 7029) that this dark state is the 21Ag state, we discuss
      the vibrational structure of the fluorescence excitation spectrum in terms of two
      manifolds of vibronic states belonging to Sd(21Ag) and S1(1B1u) states. The
      anomalous shift between excitation and dispersed fluorescence spectra observed
      earlier for terrylene in a neon matrix is discussed as a consequence of terrylene
      electronic relaxation to the low-energy dark state.

PMID- 17447745
TI  - Electronic transitions of CsC2, CsC2-, and CsC4 in neon matrixes.
AB  - The anions of CsC2 and CsC4 produced by sputtering a graphite surface with Cs+
      were mass-selected and trapped in neon matrixes at 6 K. The electronic absorption
      spectra of CsC2 and CsC4, obtained by photodetachment of electrons from the
      anions, were measured subsequently and reveal strong absorptions in the visible
      range, which resemble the known band systems of C2- and C4-, respectively. The
      origin band of CsC2 (500.4 nm) and CsC4 (442.6 nm) is shifted by approximately
      1100 or by approximately 700 cm(-1) to the blue from the position of the 0(0)0
      band of C2- or C4-. The observed system of CsC2 is assigned to the 2B2-X 2A1
      electronic transition of the T-shaped form. The CsC4 spectrum is consistent with
      a C4- chain slightly perturbed by the Cs atom. The oscillator strength of the
      observed electronic transition of CsC2 and CsC4 is an order of magnitude larger
      than for the respective carbon anions. CsC2- has a weak electronic transition,
      assigned to 1B2-X 1A1 in the C2v form, with origin band at 516.5 nm.

PMID- 17447746
TI  - Molecular structure of chloro-dodecafluorosubphthalocyanato boron(III) by gas
      phase electron diffraction and quantum chemical calculations.
AB  - The molecular structure of the chloro-dodecafluorosubphthalocyaninato boron(III)
      (F-SubPc) was determined with use of Gas Electron Diffraction (GED) and high
      level quantum chemical calculations. The present results show that the F-SubPc
      molecule has a cone-shaped configuration, isoindole units are not planar, and the
      pyrrole ring has an envelope conformation. The structure parameters in the gas
      phase are determined. Some structural details can be observed such as the
      dihedral angle about the bond connecting the pyrrole ring and the benzene ring
      being ca. 174 degrees . High-level theoretical calculations with several extended
      basis sets for this molecule have been carried out. The calculations are in very
      good agreement with experimental methods: X-ray and GED. Nevertheless, some
      disagreements particularly related to the B-Cl bond distance found in GED are
      discussed. Vibrational frequencies were computed obtaining eight values below 100
      cm-1 and three bending potentials were examined. They suggest that this molecule
      is very flexible.

PMID- 17447747
TI  - Selective urokinase-type plasminogen activator inhibitors. 4. 1-(7
      sulfonamidoisoquinolinyl)guanidines.
AB  - 1-isoquinolinylguanidines were previously disclosed as potent and selective
      inhibitors of urokinase-type plasminogen activator (uPA). Further investigation
      of this template has revealed that incorporation of a 7-sulfonamide group
      furnishes a new series of potent and highly selective uPA inhibitors. Potency and
      selectivity can be achieved with sulfonamides derived from a variety of amines
      and is further enhanced by the incorporation of sulfonamides derived from amino
      acids. The binding mode of these 1-isoquinolinylguanidines has been investigated
      by X-ray cocrystallization studies. uPA inhibitor 26 was selected for further
      evaluation based on its excellent enzyme potency (Ki 10 nM) and selectivity
      profile (4000-fold versus tPA and 2700-fold versus plasmin). In vitro, compound
      26 is able to inhibit exogenous uPA in human chronic wound fluid (IC50=0.89
      microM). In vivo, in a porcine acute excisional wound model, following topical
      delivery, compound 26 is able to penetrate into pig wounds and inhibit exogenous
      uPA activity with no adverse effect on wound healing parameters. On the basis of
      this profile, compound 26 (UK-371,804) was selected as a candidate for further
      preclinical evaluation for the treatment of chronic dermal ulcers.

PMID- 17447748
TI  - A high-throughput screen for aggregation-based inhibition in a large compound
      library.
AB  - High-throughput screening (HTS) is the primary technique for new lead
      identification in drug discovery and chemical biology. Unfortunately, it is
      susceptible to false-positive hits. One common mechanism for such false-positives
      is the congregation of organic molecules into colloidal aggregates, which
      nonspecifically inhibit enzymes. To both evaluate the feasibility of large-scale
      identification of aggregate-based inhibition and quantify its prevalence among
      screening hits, we tested 70,563 molecules from the National Institutes of Health
      Chemical Genomics Center (NCGC) library for detergent-sensitive inhibition. Each
      molecule was screened in at least seven concentrations, such that dose-response
      curves were obtained for all molecules in the library. There were 1274 inhibitors
      identified in total, of which 1204 were unambiguously detergent-sensitive. We
      identified these as aggregate-based inhibitors. Thirty-one library molecules were
      independently purchased and retested in secondary low-throughput experiments; 29
      of these were confirmed as either aggregators or nonaggregators, as appropriate.
      Finally, with the dose-response information collected for every compound, we
      could examine the correlation between aggregate-based inhibition and steep dose
      response curves. Three key results emerge from this study: first, detergent
      dependent identification of aggregate-based inhibition is feasible on the large
      scale. Second, 95% of the actives obtained in this screen are aggregate-based
      inhibitors. Third, aggregate-based inhibition is correlated with steep dose
      response curves, although not absolutely. The results of this screen are being
      released publicly via the PubChem database.

PMID- 17447749
TI  - Enhanced substituted resorcinol hydrophobicity augments tyrosinase inhibition
      potency.
AB  - The objective of the present study was to investigate to what extent the addition
      of hydrophobic residues to a 2,4-resorcinol derivative would contribute to their
      tyrosinase inhibitory potency. Hence, 3-(2,4-dihydroxyphenyl)propionic acid,
      isolated from Ficus carica, was transformed into esters, and the relationship
      between the structure of these esters to their mushroom tyrosinase inhibition
      activity was explored. The enzyme crystallographic structure, published recently
      (Matoba, Y. et al. J. Biol. Chem. 2006, 281, 8981-8990) was docked with the new
      esters, and their calculated free energy (FE) and docking energy (DE) were
      compared with the experimental IC(50) values, providing good correlations. The
      observed IC(50) of the isopropyl ester was 0.07 microM, and its interaction with
      the enzyme binding site appears to be composed of four hydrogen bonds and two
      hydrophobic interactions. It may be concluded that the addition of a hydrophobic
      moiety to 2,4-resorcinol derivatives augments tyrosinase inhibitory potency as
      was predicted from the modeling study.

PMID- 17447750
TI  - Bispyridinium dienes: histone deacetylase inhibitors with selective activities.
AB  - A novel synthetic route to the cyclostellettamines 1 using as the key step a
      microwave-mediated macrocyclic ring-closing metathesis of precursors
      bispyridinium dienes 10 followed by catalytic hydrogenation has been developed.
      The open-chain bispyridinium dienes 10 showed uniformly higher histone
      deacetylase (HDAC) inhibitory potency than the natural products. Diene 10b
      inhibited HDAC1 and was inactive on HDAC4, whereas 10a showed a weak inhibition
      of HDAC1 and a higher activity on HDAC4. Neither 10b nor 10a inhibited isoforms
      HDAC2 and HDAC3. Cell cycle analysis, cell differentiation, and apoptosis as well
      as evaluation of the acetylation status of H3 lysine tails, up-regulation of
      p21WAF1/CIP1, and alpha-tubulin acetylation induced by the dienes 10 and
      cyclostellettamines 1 were also carried out on the human leukemia U937 cell line.
      These enzymatic and functional assays suggest that 10b is a HDAC1-selective
      inhibitor and 10a is a HDAC subclass IIa-selective inhibitor.

PMID- 17447751
TI  - Small molecule designed to target metal binding site in the alpha2I domain
      inhibits integrin function.
AB  - Integrin alpha2beta1 is a potential target molecule in drug development. We have
      established "design" criteria for molecules that bind to the "closed"
      conformation of alpha2I domain via Mg(2+) in MIDAS (metal ion dependent adhesion
      site) while simultaneously forming interactions with neighboring amino acid
      residues. Specific tetracyclic Streptomyces products belonging to the group of
      aromatic polyketides fulfill our criteria and inhibit alpha2beta1 integrin. All
      previously described inhibitors of alphaI domain integrins act in an allosteric
      manner.

PMID- 17447752
TI  - New diphenylacetylenes as probes for positron emission tomographic imaging of
      amyloid plaques.
AB  - A series of 18F fluoropegylated diphenylacetylenes as probes for binding to Abeta
      plaques were successfully prepared. These relatively rigid acetylenes, 12a, 12b,
      14a, and 14b, displayed high binding affinities in postmortem AD brain
      homogenates (Ki ranging from 1.2 to 2.9 nM). In vivo biodistribution in normal
      mice exhibited excellent initial brain penetrations (4.42, 4.55, 5.41, and 6.78%
      dose/g at 2 min for [18F]12a, 12b, 14a, and 14b, respectively). [18F]12b and
      [18F]14b, with a longer fluoropegylated unit, that is, n=3, showed faster brain
      washout at 30 min postinjection (0.42 and 1.57% dose/g) as compared to the
      shorter fluoropegylated chain ligands, that is, [18F]12a and [18F]14a (1.03 and
      3.69% dose/g). Autoradiography and homogenate binding confirmed the high binding
      signal due to Abeta plaques. These preliminary results suggest that the novel
      diphenylacetylenes may be potentially useful for imaging of Abeta plaques in the
      brain of patients with Alzheimer's disease.

PMID- 17447753
TI  - Analysis of HIV wild-type and mutant structures via in silico docking against
      diverse ligand libraries.
AB  - The FightAIDS@Home distributed computing project uses AutoDock for an initial
      virtual screen of HIV protease structures against a broad range of 1771 ligands
      including both known protease inhibitors and a diverse library of other ligands.
      The volume of results allows novel large-scale analyses of binding energy
      "profiles" for HIV structures. Beyond identifying potential lead compounds, these
      characterizations provide methods for choosing representative wild-type and
      mutant protein structures from the larger set. From the binding energy profiles
      of the PDB structures, a principal component analysis based analysis identifies
      seven "spanning" proteases. A complementary analysis finds that the wild-type
      protease structure 2BPZ best captures the central tendency of the protease set.
      Using a comparison of known protease inhibitors against the diverse ligand set
      yields an AutoDock binding energy "significance" threshold of -7.0 kcal/mol
      between significant, strongly binding ligands and other weak/nonspecific binding
      energies. This threshold captures nearly 98% of known inhibitor interactions
      while rejecting more than 95% of suspected noninhibitor interactions. These
      methods should be of general use in virtual screening projects and will be used
      to improve further FightAIDS@Home experiments.

PMID- 17447754
TI  - Synthesis and spectroscopic characterization of copper(II)-nitrito complexes with
      hydrotris(pyrazolyl)borate and related coligands.
AB  - This study focuses on the geometric (molecular) structures, spectroscopic
      properties, and electronic structures of copper(II)-nitrito complexes as a
      function of second coordination sphere effects using a set of closely related
      coligands. With anionic hydrotris(pyrazolyl)borate ligands, one nitrite is bound
      to copper(II). Depending on the steric demand of the coligand, the coordination
      mode is either symmetric or asymmetric bidentate, which leads to different ground
      states of the resulting complexes as evident from EPR spectroscopy. The
      vibrational spectra of these compounds are assigned using isotope substitution
      and DFT calculations. The results demonstrate that nu sym(N-O) occurs at higher
      energy than nu asym(N-O), which is different from the literature assignments for
      related compounds. UV-vis absorption and MCD spectra are presented and analyzed
      with the help of TD-DFT calculations. The principal binding modes of nitrite to
      Cu(II) and Cu(I) are also investigated applying DFT. Using a neutral
      tris(pyrazolyl)methane ligand, two nitrite ligands are bound to copper. In this
      case, a very unusual binding mode is observed where one nitrite is eta1-O and the
      other one is eta1-N bound. This allows to study the properties of coordinated
      nitrite as a function of binding mode in one complex. The N-coordination mode is
      easily identified from vibrational spectroscopy, where N-bound nitrite shows a
      large shift of nu asym(N-O) to >1400 cm-1, which is a unique spectroscopic
      feature. The optical spectra of this compound exhibit an intense band around 300
      nm, which might be attributable to a nitrite to Cu(II) CT transition. Finally,
      using a bidentate neutral bis(pyrazolyl)methane ligand, two eta1-O coordinated
      nitrite ligands are observed. The vibrational and optical (UV-vis and MCD)
      spectra of this compound are presented and analyzed.

PMID- 17447755
TI  - Density functional theory and ab initio study of electronic and electrochemistry
      properties of the tetranuclear sandwich complex [FeIII4(H2O)2(PW9O34)2]6-.
AB  - Quantum chemistry calculations have been performed to unravel the electronic and
      electrochemical properties of a FeIII-sandwich polyoxometalate. Using a
      combination of methods, it is shown that in these clusters the first reduction
      occurs in the so-called external Fe, which is bonded to a water ligand.
      Calculations also show that the electron reductions are coupled with protonation
      processes, in full agreement with existing experimental results.

PMID- 17447756
TI  - Hydrothermal vanadium fluoride chemistry: four new V3+ chain structures.
AB  - An exploratory study of the hydrothermal chemistry of vanadium in HF solutions
      has resulted in the preparation of four new vanadium (III) fluorides with
      chainlike structural motifs. [NH4]2[VF5] (1) and [C2N2H10][VF5] (2) feature
      infinite chains of trans corner-sharing VF4F2/2 octahedra, [C4N2H6][VF5].H2O (3)
      has cis corner-sharing [VF4F2/2]infinity chains, and [C10N2H8][VF3] (4) has trans
      corner-sharing [VF2F2/2]infinity chains bridged into sheets by the 4,4'-bipy
      linker. All four compounds exhibit antiferromagnetic behavior.

PMID- 17447757
TI  - Monocyclic di- and triphosphinophosphonium cations: new foundational frameworks
      for catena-phosphorus chemistry.
AB  - The synthesis and characterization for trifluoromethanesulfonate (triflate) salts
      of the first definitive examples of cyclotriphosphinophosphonium and
      cyclodiphosphinophosphonium cations are described, representing new prototypical
      frameworks in the rational and systematic development of catena-phosphorus
      chemistry. Addition of methyl triflate (MeOTf) or triflic acid (HOTf) to
      cyclotetraphosphines (tBuP)4 (1a) or (CyP)4 (1b) gives [(tBuP)3PtBuMe][OTf]
      (2a[OTf]), [(CyP)3PCyMe][OTf] (2b[OTf]), [(tBuP)3PtBuH][OTf] (3a[OTf]), and
      [(CyP)3PCyH][OTf] (3b[OTf]), respectively. Cyclotriphosphine (tBuP)3 (4a) reacts
      with HOTF or Me2PCl/Me3SiOTf to give the ring expanded cations 3a[OTf] and
      [(tBuP)3PMe2][OTf] (5[OTf]), respectively, but reactions with MeOTf and HCl give
      cyclic diphosphinophosphonium cation [(tBuP)2PtBuMe][OTf] (6a[OTf]) and ring
      opened triphosphine HtBuP-PtBu-PtBuCl (7), respectively. The analogous
      diphosphinophosphonium cation [(CyP)2PCyMe][OTf] (6b[OTf]) is formed along with
      2b[OTf] in reactions of MeOTf with (CyP)3 (4b). Compounds 2a[OTf], 2b[OTf],
      3a[OTf], 5[OTf], and 6a[OTf] have been crystallographically characterized. 1H NMR
      spectra of 2a[OTf], 2b[OTf], 5[OTf], and 6a[OTf] demonstrate that 3JPH coupling
      is only observed for methyl protons if they are in a cis orientation to the lone
      pairs on the adjacent phosphine sites.

PMID- 17447758
TI  - Exceptional self-penetrating networks containing unprecedented quintuple-stranded
      molecular braid, 9-fold meso helices, and 17-fold interwoven helices.
AB  - Self-assembly of long V-shaped ligands and d10 metal salts in the presence of a
      linear bidentate ligand affords two unprecedented self-penetrating coordination
      networks {[Zn4(bptc)2(bpy)4].(C5H3N).4H2O}n (1) and
      {[Cd2(sdba)2(bpy)(H2O)2].2H2O}n (2) (bptc = 3,3',4,4'
      benzophenonetetracarboxylate, sdba = 4,4'-sulfonyldibenzoate, bpy = 4,4'
      bipyridine). Their structures were determined by single-crystal X-ray diffraction
      analyses and further characterized by elemental analyses, IR spectra, X-ray
      powder diffraction, and TG analyses. 1 adopts a novel 3D framework containing
      three types of molecular braids, among which the quintuple-stranded molecular
      braid represents the highest-stranded molecular braid presently known for
      entangled systems. 2 is an uncommon self-penetrating 2D network containing pseudo
      Borromean links and double-stranded helices. More interestingly, when the strong
      hydrogen bonds between layers are taken into account, the resulting net of 2
      becomes an eight-connected 3D self-penetrating network with an unprecedented
      (421.67) topology, which represents the highest connected topology presently
      known in self-penetrating systems. Furthermore, the photoluminescent properties
      of 1 and 2 were studied.

PMID- 17447759
TI  - Redox-induced solid-solid phase transformation of TCNQ microcrystals into
      semiconducting Ni[TCNQ]2(H2O)2 nanowire (flowerlike) architectures: a combined
      voltammetric, spectroscopic, and microscopic study.
AB  - The facile solid-solid phase transformation of TCNQ microcrystals into
      semiconducting and magnetic Ni[TCNQ]2(H2O)2 nanowire (flowerlike) architectures
      is achieved by reduction of TCNQ-modified electrodes in the presence of Ni2+(aq)
      containing electrolytes. Voltammetric probing revealed that the chemically
      reversible TCNQ/Ni[TCNQ]2(H2O)2 conversion process is essentially independent of
      electrode material and the identity of nickel counteranion but is significantly
      dependent on scan rate, Ni2+(aq) electrolyte concentration, and the method of
      solid TCNQ immobilization (drop casting or mechanical attachment). Data analyzed
      from cyclic voltammetric and double-potential step chronoamperometric experiments
      are consistent with formation of the Ni[TCNQ]2(H2O)2 complex via a rate
      determining nucleation/growth process that involves incorporation of Ni2+(aq)
      ions into the reduced TCNQ crystal lattice at the triple phase
      TCNQ|electrode|electrolyte interface. The reoxidation process, which includes the
      conversion of solid Ni[TCNQ]2(H2O)2 back to TCNQ0 crystals, is also controlled by
      nucleation/growth kinetics. The overall redox process associated with this
      chemically reversible solid-solid transformation, therefore, is described by the
      equation: TCNQ0(S) + 2e- + Ni2+(aq)+ 2 H2O <==> {Ni[TCNQ]2(H2O)2}(S). SEM
      monitoring of the changes that accompany the TCNQ/Ni[TCNQ]2(H2O)2 transformation
      revealed that the morphology and crystal size of electrochemically generated
      Ni[TCNQ]2(H2O)2 are substantially different from those of parent TCNQ crystals.
      Importantly, the morphology of Ni[TCNQ]2(H2O)2 can be selectively manipulated to
      produce either 1-D/2-D nanowires or 3-D flowerlike architectures via careful
      control over the experimental parameters used to accomplish the solid-solid phase
      interconversion process.

PMID- 17447760
TI  - A new branched phenanthroline derivative ligand: synthesis, solution chemistry,
      and crystal structures of copper(II) and zinc(II) complexes.
AB  - The synthesis and characterization of the new ligand 2,9-bis[N,N-bis(2
      aminoethyl)aminomethyl]-1,10-phenanthroline (L) are reported. L contains two
      diethylenetriamine units connected on the central nitrogen atom by a 1,10
      phenanthroline group forming a symmetrical branched ligand. The basicity and
      binding properties of L toward Cu(II) and Zn(II) in aqueous solution were
      determined by means of potentiometric, UV-vis, fluorescence, and 1H and 13C NMR
      techniques. L behaves as pentaprotic base under the experimental conditions used;
      from HL+ to H4L4+ species it is the secondary amine functions that are protonated
      while in the H5L5+ species also the phenanthroline is involved in protonation. L
      does not show fluorescence properties in the range of pH (0-14) investigated. It
      forms both mono- and dinuclear stable species where the phenanthroline is
      directly involved with both nitrogens in the coordination of the first metal
      which is coordinated in a pentacoordination environment also by one dien unit.
      The other dien unit undergoes easy protonation in the mononuclear complex while
      it binds the second metal in the dinuclear species. For this reason, L, in
      providing two different binding areas for metal coordination, behaves as an
      unsymmetrical compartmental ligand; one area is formed by one dien unit and by
      the phenanthroline, and the other by the remaining dien unit. This produces
      unsymmetrical metal complexes both for the mono- and dinuclear species; however,
      the role of the binding areas is fast exchanging in aqueous solution, at least on
      the NMR time scale. Solution studies and the three crystal structures of the
      [Zn(H2L)]4+, [[Cu(H2L)](ClO4)]3+, and [[Cu2LCl2](ClO4)]+ species highlight the
      unsymmetrical compartmental behavior of L as well as the host properties of the
      complexes in adding exogenous ligands such as hydroxide, pherchlorate, and
      chloride anions.

PMID- 17447761
TI  - Metal-ion selectivity produced by C-alkyl substituents on the bridges of
      chelating ligands: the importance of short H-H nonbonded van der Waals contacts
      in controlling metal-ion selectivity. A thermodynamic, molecular mechanics, and
      crystallographic study.
AB  - The effect on metal-ion selectivity of the use of cyclohexenyl bridges in ligands
      in place of ethylene bridges is examined (selectivity is defined as the
      difference in log K1 for one metal ion relative to that of another with the same
      ligand). The syntheses of N,N'-bis(2-hydroxycyclohexyl)ethane-1,2-diamine (Cy2
      en), N,N'-bis(2-hydroxycyclohexyl)propane-1,3-diamine (Cy2-tn), and 1,7-bis(2
      hydroxycyclohexyl)-1,4,7-triazaheptane (Cy2-dien) are reported. The crystal
      structures of [Cu(Cy2-tn)(H2O)](ClO4)2 (1) and [Cu(Cy2-dien)](ClO4)2 (2) are
      reported. Characteristics of 1: monoclinic, Pn space group, a=11.627(2) A,
      b=7.8950(10) A, c=12.737(8) A, beta=98.15(3) degrees, Z=2, R=0.0524.
      Characteristics of 2: orthorhombic, Pbca space group, a=21.815(16) A, b=8.525(7)
      A, c=25.404(14) A, Z=8, R=0.0821. Structure 1 has the Cu(II) atom coordinated in
      the plane of the ligand to the two N donors and two O donors, with a long bond to
      an axially coordinated water molecule. 2 has three N donors, and one hydroxyl O
      donor from the ligand is coordinated in the plane around the Cu(II) atom, with
      the second hydroxyl O donor of the ligand occupying an axial site with a long Cu
      O bond. The salient feature of both structures is the short H-H nonbonded
      distance between H atoms on the cyclohexenyl bridges and H atoms on the ethylene
      bridges of the ligand. These short contacts are important in explaining the metal
      ion selectivities of these ligands. Formation constants, determined by glass
      electrode potentiometry, for the Cy2-en (Cu(II), Ni(II), Zn(II), Cd(II), Pb(II)),
      Cy2-dien (Cu(II), Zn(II), Cd(II), Pb(II)), and Cy2-tn (Cu(II), Zn(II), Cd(II))
      complexes are reported. These all show a strong shift in selectivity toward
      smaller metal ions compared with the analogous ligands, where ethylene bridges
      are present in place of the cyclohexenyl bridges of the ligands studied here.
      Molecular mechanics (MM) calculations are used to analyze these changes in
      selectivity. These calculations show that the short H-H contacts become shorter
      with increasing metal-ion size, which is suggested as the cause of the shift in
      the selectivity of ligands in favor of smaller metal ions when ethylene bridges
      are replaced with cyclohexenyl bridges. MM calculations are also used to
      rationalize, in terms of short H-H contacts, the fact that when the chelate ring
      contains two neutral O donors, more stable complexes result with cis placement of
      the donor atoms on the cyclohexenyl bridge, but with two N donors, trans
      placement of the donor atoms results in more stable complexes.

PMID- 17447762
TI  - Protein design: reengineering cellular retinoic acid binding protein II into a
      rhodopsin protein mimic.
AB  - Rational redesign of the binding pocket of Cellular Retinoic Acid Binding Protein
      II (CRABPII) has provided a mutant that can bind retinal as a protonated Schiff
      base, mimicking the binding observed in rhodopsin. The reengineering was
      accomplished through a series of choreographed manipulations to ultimately orient
      the reactive species (the epsilon-amino group of Lys132 and the carbonyl of
      retinal) in the proper geometry for imine formation. The guiding principle was to
      achieve the appropriate Burgi-Dunitz trajectory for the reaction to ensue.
      Through crystallographic analysis of protein mutants incapable of forming the
      requisite Schiff base, a highly ordered water molecule was identified as a key
      culprit in orienting retinal in a nonconstructive manner. Removal of the ordered
      water, along with placing reinforcing mutations to favor the desired orientation
      of retinal, led to a triple mutant CRABPII protein capable of nanomolar binding
      of retinal as a protonated Schiff base. The high-resolution crystal structure of
      all-trans-retinal bound to the CRABPII triple mutant (1.2 A resolution)
      unequivocally illustrates the imine formed between retinal and the protein.

PMID- 17447763
TI  - Ab initio study of the excited-state deactivation pathways of protonated
      tryptophan and tyrosine.
AB  - In recent experiments, the excited-state lifetimes of protonated aromatic amino
      acids (TrpH+ and TyrH+) have been recorded by means of pump-probe
      photodissociation technique. The lifetime of TyrH+ is much longer than that of
      TrpH+, which has been initially rationalized on the basis of a simple
      phenomenological model. Besides, specific photofragments including the formation
      of radical cation after hydrogen loss are observed for TrpH+ that are not found
      for TyrH+. The ab initio calculations reported here for TrpH+ and TyrH+ using a
      coupled-cluster method are meant to track the rich photochemistry of these
      protonated amino acids following UV excitation.

PMID- 17447764
TI  - The solvent cage effect: is there a spin barrier to recombination of transition
      metal radicals?
AB  - This investigation explored whether there is a spin barrier to recombination of
      first- and second-row transition metal-centered radicals in a radical cage pair.
      To answer this question, the recombination efficiencies of photochemically
      generated radical cage pairs (denoted as FcP) were measured in the presence and
      absence of an external heavy atom probe. Two methods were employed for measuring
      the cage effect. The first method was femtosecond pump-probe transient absorption
      spectroscopy, which directly measured FcP from reaction kinetics, and the second
      method (referred to herein as the "steady-state" method) obtained FcP from
      quantum yields for the radical trapping reaction with CCl4 as a function of
      solvent viscosity. Both methods generated radical cage pairs by photolysis
      (lambda = 515 nm for the pump probe method and lambda = 546 nm for the steady
      state method) of Cp'2Mo2(CO)6 (Cp' = eta(5)-C5H4CH3). In addition, radical cage
      pairs generated from Cp'2Fe2(CO)4 and Cp*2TiCl2 (Cp* = eta(5)-C5(CH3)5) were
      studied by the steady-state method. The pump-probe method used p-dichlorobenzene
      as the heavy atom perturber, whereas the steady-state method used iodobenzene.
      For both methods and for all the radical caged pairs investigated, there were no
      observable heavy atom effects, from which it is concluded there is no spin
      barrier to recombination.

PMID- 17447766
TI  - Nanoparticle self-assembly gated by logical proteolytic triggers.

PMID- 17447767
TI  - Gas-phase tautomeric equilibrium of 4-hydroxypyrimidine with its ketonic forms: a
      free jet millimeterwave spectroscopy study.
AB  - 4-Hydroxypyrimidine (4HP) has two conformational forms (the hydroxyl hydrogen cis
      or trans with respect to the adjacent nitrogen), which are in tautomeric
      equilibrium with two ketonic forms, 4-pyrimidinone (4PO) and 6-pyrimidinone
      (6PO). We have investigated the free jet absorption millimeterwave spectrum of
      this system, assigning the rotational spectra of 4HPcis and 4PO; the latter
      species is more stable by 2.0(9) kJ/mol. No lines corresponding to the trans
      isomer of 4-hydroxypyridine and to 6PO have been observed.

PMID- 17447768
TI  - ssDNA templated self-assembly of chromophores.

PMID- 17447769
TI  - Stretched poly(acrylonitrile) as a scalable alignment medium for DMSO.

PMID- 17447771
TI  - Luminescent sensing of dicarboxylates in water by a bismacrocyclic dinuclear
      Eu(III) conjugate.
AB  - The design, synthesis, and characterization of a novel dinuclear Eu(III)
      bismacrocyclic conjugate 1.Eu2 as a delayed luminescent lanthanide sensor for
      dicarboxylates is discussed. The sensor was shown to bind small dicarboxylic
      acids such as aspartic, malonic, succinic, or glutaric acid in pH 6.5 solutions.
      However, only malonic acid gave rise to selective Eu(III) luminescent
      enhancements, as the emission was reduced for all of the other acids.

PMID- 17447772
TI  - Combinatorial mutasynthesis of flavonoid analogues from acrylic acids in
      microorganisms.
AB  - Flavonoids are plant secondary metabolites often used as nutraceutical
      supplements, but a growing number of unnatural flavonoids are being investigated
      as therapeutic agents. Cultures of Saccharomyces cerevisiae expressing
      recombinant flavonoid enzymes, including 4-coumaroyl:CoA ligase (4CL), chalcone
      synthase (CHS), chalcone isomerase (CHI), and flavanone 3beta-hydroxylase (FHT),
      produced novel flavanones and dihydroflavonols when fed with a number of aromatic
      acrylic acids. The flavonoid network also exhibited broad substrate specificity
      by converting muconic acid into a unique polypropanoid.

PMID- 17447773
TI  - Photochemical DNA activation.
AB  - A new photocaged nucleoside was synthesized and incorporated into DNA with the
      use of standard synthesis conditions. This approach enabled the disruption of
      specific H-bonds and allowed for the analysis of their contribution to the
      activity of a DNAzyme. Brief irradiation with nonphotodamaging UV light led to
      rapid decaging and almost quantitative restoration of DNAzyme activity. The
      developed strategy has the potential to find widespread application in the light
      induced regulation of oligonucleotide function.

PMID- 17447774
TI  - Electron-donating perylene tetracarboxylic acids for dye-sensitized solar cells.
AB  - Novel perylene imide derivatives with both electron-donating and bulky
      substituents have been synthesized for dye-sensitized solar cells. The power
      conversion efficiency reached 2.6%, which is the highest value among perylene
      sensitized TiO2 solar cells.

PMID- 17447775
TI  - 2-alkenoyl pyridine N-oxides, highly efficient dienophiles for the
      enantioselective Cu(II)-bis(oxazoline) catalyzed Diels-Alder reaction.
AB  - 2-Alkenoyl pyridine N-oxides are introduced as a new kind of efficient
      dienophiles for the Cu(II)-bis(oxazoline) (BOX) catalyzed enantioselective Diels
      Alder reaction affording higher reactivity and enantioselectivity (ee's up to
      96%) than the corresponding nonoxidized 2-alkenoyl pyridines.

PMID- 17447776
TI  - The Kulinkovich reaction in the synthesis of constrained n,n-dialkyl
      neurotransmitter analogues.
AB  - An intermolecular Ti(IV)-mediated cyclopropanation reaction has been used to
      synthesize substituted 2-phenylcyclopropylamines and constrained analogues of the
      neurotransmitters histamine and tryptamine. Many hydroxy- and methoxy-substituted
      phenylcyclopropylamines are known to inhibit monoamine oxidase and have been
      shown to mimic hallucinogens. These compounds were made in 1 to 5 steps from
      readily available starting materials.

PMID- 17447777
TI  - Bronsted acid-catalyzed benzylation of 1,3-dicarbonyl derivatives.
AB  - The direct alkylation of 1,3-dicarbonyl compounds with benzylic alcohols is shown
      to be efficiently catalyzed by simple Bronsted acids such as triflic acid (TfOH)
      and p-toluenesulfonic acid (PTS) to give rise to monoalkylated dicarbonyl
      derivatives in high yields. In the absence of the nucleophile, substituted
      alkenes, generated through a formal dimerization reaction, are obtained. The
      reactions are carried out in air using undried solvents, with water being the
      only side product of the process.

PMID- 17447778
TI  - Catalytic asymmetric formation of beta-sultams.
AB  - beta-Sultams, highly strained sulfonyl analogues of beta-lactams, were prepared
      enantio- and diastereoselectively by tertiary amine catalyzed [2 + 2]
      cycloaddition reactions. The title compounds are practical precursors of highly
      enantioenriched biologically interesting beta-aminosulfonyl derivatives.

PMID- 17447779
TI  - Size effect of encaged clusters on the exohedral chemistry of endohedral
      fullerenes: a case study on the pyrrolidino reaction of ScxGd3-xN@C80 (x = 0-3).
AB  - We report a combined experimental and theoretical investigation on the
      regiochemistry of a series of TNT endohedral fullerenes ScxGd3-xN@C80 (x = 0-3)
      in 1,3-dipolar cycloadditions, which demonstrates that the regioselectivity of
      the TNT-based endohedral fullerenes ScxGd3-xN@C80 (x = 0-3) in the exohedral
      cycloadditions depends remarkably on the size of the encaged cluster.

PMID- 17447780
TI  - Chemoselective amination of 5-bromo-2-chloro-3-fluoropyridine.
AB  - The chemoselective functionalization of 5-bromo-2-chloro-3-fluoropyridine (1c) is
      described. Catalytic amination conditions (Pd2dba3, Xantphos, base) afford
      exclusively the bromide substitution product (2) for both secondary amines and
      primary anilines. A reversal in chemoselectivity is observed under neat
      conditions in the absence of palladium catalysis, with substitution at the 2
      chloro position preferred to generate 3. Last, selective substitution of the 3
      fluoro group is achieved under SNAr conditions to afford the dihalo adduct (4).

PMID- 17447781
TI  - Copper(II) carboxylate promoted intramolecular diamination of terminal alkenes:
      improved reaction conditions and expanded substrate scope.
AB  - The copper(II) carboxylate promoted diamination reaction has been improved by the
      use of the organic soluble copper(II) neodecanoate [Cu(ND)2]. Cu(ND)2 allowed the
      less-polar solvent dichloroethane (DCE) to be used, and as a consequence,
      decomposition of less-reactive substrates could be avoided. High
      diastereoselectivity was observed in the synthesis of 2,5-disubstituted
      pyrrolidines. Ureas, bis(anilines), and alpha-amido pyrroles derived from 2
      allylaniline could also participate in the diamination reaction.

PMID- 17447782
TI  - Total synthesis of anibamine, a novel natural product as a chemokine receptor
      CCR5 antagonist.
AB  - The total synthesis of anibamine, the first and only natural product known as a
      chemokine receptor CCR5 antagonist, is reported herein. Anibamine was synthesized
      from acetylacetone and cyanoacetamide in 10 steps.

PMID- 17447783
TI  - Comment on nutrients and antioxidant molecules in yellow plums (Prunus domestica
      L.) from conventional and organic productions: a comparative study.

PMID- 17447784
TI  - Identification and some properties of anthocyanin isolated from Zuiki, stalk of
      Colocasia esculenta.
AB  - Zuiki, a stalk of taro (Colocasia esculenta), is a traditional vegetable in
      Japan. Raw zuiki is often boiled and vinegared to eat. The surface color of zuiki
      is reddish. Here, we isolated a red pigment from zuiki and identified it as
      cyanidin 3-rutinoside using instrumental analyses. The color of zuiki disappeared
      by boiling, but the zuiki turned red again in an acetic acid solution. It seems
      that the cyanidin 3-rutinoside that exists on the surface of zuiki elutes in
      boiling water and then, the pigment that seeps out from the inside of the zuiki
      is exposed to an acid solution, and its surface turns red again. The radical
      scavenging activity of purified zuiki anthocyanin was 114 mg equivalent to BHT/g.
      About half of the anthocyanin in fresh zuiki was washed out by boiling, and the
      radical scavenging activity of zuiki was definitely reduced.

PMID- 17447786
TI  - Photodegradation of metolachlor applying UV and UV/H2O2.
AB  - Metolachlor is one of the most widely used herbicides in the world for
      controlling weeds. It has been detected in both ground and surface waters in the
      United States, and there are rising concerns in regard to its health risks and in
      developing effective treatment processes for its removal from water. Degradation
      of metolachlor via ultraviolet (UV) photolysis and an UV/hydrogen peroxide
      advanced oxidation process (AOP) was studied. The quantum yield of metolachlor at
      254 nm was found to be 0.302 +/- 0.001 mol E-1 through direct UV photolysis in
      the range of pH 6-8. The second-order rate constant of the reaction between
      metolachlor and hydroxyl radical was determined to be 9.07 (+/-0.21) x 10(9) M-1
      s-1 by using a competition kinetics model that utilized nitrobenzene as a
      reference compound. In addition, these parameters were successfully applied in
      modeling the kinetics of elimination of metolachlor using an UV/H2O2 process in
      both laboratory and natural waters. The formation of several photolysis
      byproducts was identified using gas chromatography/mass spectrometry, and a
      scheme for the metolachlor photodegradation pathway is proposed.

PMID- 17447787
TI  - Characterization of protein fractions from Bt-transgenic and non-transgenic maize
      varieties using perfusion and monolithic RP-HPLC. Maize differentiation by
      multivariate analysis.
AB  - Protein fractions from transgenic Bt and non-transgenic maize varieties,
      extracted by the Osborne solvent fraction procedure, were characterized for the
      first time by perfusion and monolithic RP-HPLC in very short analysis times.
      Albumins and globulins from different transgenic Bt maizes as well as from their
      non-transgenic isogenic varieties were eluted in four peaks using perfusion RP
      HPLC, whereas prolamins and glutelins were separated in seven peaks. Monolithic
      RP-HPLC enabled the separation of maize proteins in a large number of peaks
      showing 6 and 10 main peaks for albumins and globulins, respectively. Prolamins
      migrated at retention times higher than 5 min as seven peaks, whereas glutelins
      were separated in three main peaks appearing at retention times higher than 6.0
      min. Moreover, chromatograms of the whole protein extracts showed 8 and 11
      components for perfusion and monolithic RP-HPLC, respectively. A comparison of
      the chromatograms of the whole protein extracts relative to transgenic and non
      transgenic varieties evidenced quantitative differences on the percentages of
      area, mainly for peaks 2 and 3 by perfusion RP-HPLC and for peaks 3 and 7 by
      monolithic RP-HPLC. A discriminant analysis based on these proteic profiles was
      carried out to classify and predict transgenic Bt maize lines, achieving 100%
      correct classification using perfusion RP-HPLC.

PMID- 17447788
TI  - Evaluation of 2-alkylcyclobutanones in irradiated cured pork products during
      vacuum-packed storage.
AB  - The 2-Alkylcyclobutanones (2-ACBs) content was determined in three Italian cured
      pork products (salame Milano, coppa, and pancetta) irradiated at different
      targeted irradiation doses (2, 5, and 8 kGy) during vacuum-packed storage. Among
      2-ACBs, three different compounds were investigated, namely, 2
      dodecylcyclobutanone, 2-tetradecylcyclobutanone, and 2-(tetradec-5'
      enyl)cyclobutanone. 2-ACBs were absent from the nonirradiated samples, whereas
      their content increased with irradiation dose. Their presence was recorded
      occasionally at 2 kGy and constantly at higher irradiation doses (5 and 8 kGy).
      The plot of 2-ACBs content against targeted irradiation doses showed an
      exponential relationship. The effect of vacuum-packed storage time on the 2-ACBs
      content was dependent on the irradiation dose. During vacuum-packed storage for
      up to 60 days, the 2-ACBs content remained unchanged in the cured pork products
      irradiated at 2 and 5 kGy, whereas a significant increase was observed in the
      pork products irradiated at 8 kGy.

PMID- 17447789
TI  - Mechanisms of alkylpyrazine formation in a potato model system containing added
      glycine.
AB  - The use of glycine to limit acrylamide formation during the heating of a potato
      model system was also found to alter the relative proportions of alkylpyrazines.
      The addition of glycine increased the quantities of several alkylpyrazines, and
      labeling studies using [2-13C]glycine showed that those alkylpyrazines which
      increased in the presence of glycine had at least one 13C-labeled methyl
      substituent derived from glycine. The distribution of 13C within the pyrazines
      suggested two pathways by which glycine, and other amino acids, participate in
      alkylpyrazine formation, and showed the relative contribution of each pathway.
      Alkylpyrazines that involve glycine in both formation pathways displayed the
      largest relative increases with glycine addition. The study provided an insight
      into the sensitivity of alkylpyrazine formation to the amino acid composition in
      a heated food and demonstrated the importance of those amino acids that are able
      to contribute an alkyl substituent. This may aid in estimating the impact of
      amino acid addition on pyrazine formation, when amino acids are added to foods
      for acrylamide mitigation.

PMID- 17447790
TI  - Which impact for beta-damascenone on red wines aroma?
AB  - beta-Damascenone, a C-13 norisoprenoid compound, is usually presented as an
      impact odorant in red wines. Its direct contribution to their aroma was
      investigated. Both free beta-damascenone and beta-damascenone precursors were
      isolated from various French red wines and then analyzed by gas chromatography
      mass spectrometry, revealing concentrations in the vicinity of 1 and 2 microg/L
      for free compounds and both forms, respectively. Gas chromatography-olfactometry
      analyses were also performed on dilutions of both red wine extracts and pure beta
      damascenone. The very low detection threshold in olfactometry for this compound
      explains why it is found at the highest dilution factor in aroma extract dilution
      analysis methods. Moreover, determination of beta-damascenone's odor thresholds
      confirmed the huge importance of the matrix: beta-Damascenone is characterized by
      a very low perception threshold in hydroalcoholic solution as compared to red
      wine, where it is over 1000-fold higher. In hydroalcoholic solution, beta
      damascenone enhanced fruity notes of ethyl cinnamate and caproate and masked the
      herbaceous aroma of IBMP. Globally, these results suggested that beta-damascenone
      has more an indirect than a direct impact on red wine aroma.

PMID- 17447791
TI  - Separation of selenium, zinc, and copper compounds in bovine whey using size
      exclusion chromatography linked to inductively coupled plasma mass spectrometry.
AB  - To study the role of trace elements for the quality and nutritional value of
      bovine milk, the distribution of selenium, zinc, and copper in whey was
      investigated using a method linking size exclusion chromatography to inductively
      coupled plasma mass spectrometry (SEC-ICP-MS). Three major peaks were detected
      for selenium, two peaks for zinc, and five peaks for copper. More than 65% of the
      selenium was found in protein fractions, mainly in fractions coinciding with the
      major whey proteins beta-lactoglobulin and alpha-lactalbumin. All zinc was
      associated with low molecular weight compounds (<5 kDa) and one of these
      compounds was probably citrate. More than 60% of the copper eluted in protein
      fractions and two of the five major peaks probably contained metallothionein and
      citrate. This method was used to compare milk and whey produced by organic and
      conventional feeding procedures. The selenium content in whey and desalted milk
      produced using organic regimens was significantly lower than that in conventional
      samples. Moreover, the proportion of selenium in protein fractions of organic
      whey was significantly smaller than that in conventional whey, but the
      distributions of zinc and copper did not differ. This study showed that with the
      SEC-ICP-MS technique the distribution profiles of several trace elements in whey
      could be studied in the same run and that the selenium profile differed in whey
      produced by organic and conventional procedures.

PMID- 17447792
TI  - Effects of processing and of storage on the stability of pantothenic acid in sea
      buckthorn products (Hippophae rhamnoides L. ssp. rhamnoides) assessed by stable
      isotope dilution assay.
AB  - A stable isotope dilution assay for quantification of pantothenic acid in sea
      buckthorn berries, juice, and concentrate using a four-fold labeled isotopologue
      of vitamin B5 as the internal standard was adopted using reversed phase liquid
      chromatography-mass spectrometry with electrospray ionization. Because of a rapid
      sample clean up procedure without the necessity of external calibration, this
      methodology permits the accurate analysis of a high number of samples within a
      short time. Sea buckthorn juice was stored at 25 and 40 degrees C for up to 7
      days to determine the effects of storage temperature on the stability of
      pantothenic acid. Analysis of kinetic data suggested that the degradation follows
      a first-order model. The results of the experiments showed that storage of sea
      buckthorn juice for 7 days at ambient temperature (25 degrees C) already resulted
      in a significant degradation of pantothenic acid of about 18%. The processing
      effects of juice production and subsequent concentration revealed a decrease of
      about 6-7% in the juice and of 23% in the juice concentrate.

PMID- 17447793
TI  - Direct automatic determination of bitterness and total phenolic compounds in
      virgin olive oil using a pH-based flow-injection analysis system.
AB  - Flavor and taste are sensorial attributes of virgin olive oil (VOO) highly
      appreciated by consumers. Among the organoleptic properties of VOO, bitterness is
      related to the natural phenolic compounds present in the oil. Sensorial analysis
      is the official method to evaluate VOO flavor and bitterness, which requires
      highly specialized experts. Alternatively, methods based on physicochemical
      determinations could be useful for the industry. The present work presents a flow
      injection analysis system for the direct automatic determination of bitterness
      and total phenolic compounds in VOO without prior isolation, based on the
      spectral shift undergone by phenolic compounds upon pH variation. This system
      enables a complete automation of the process, including dilution of the sample
      and its sequential injection into buffer solutions of acidic and alkaline pH. The
      variation of the absorbance at 274 nm showed a high correlation with bitterness
      and the total phenolic content of VOO, due to the close relationship between
      these two parameters. Thus, the proposed method determines the bitterness and
      phenolic compounds, with results similar to those from reference methods
      (relative errors ranging from 1% to 8% for bitterness and from 2% and 7% for
      phenolic compounds). The precision evaluated at two levels of both parameters
      ranged between 0.6% and 1.5% for bitterness and between 0.7% and 2.6% for
      phenolic compounds.

PMID- 17447794
TI  - A convenient route to the synthesis of isotopomeric dihydro-2(3H)furanones.
AB  - A general synthetic procedure leading to isotopomeric dihydro-2(3H)furanones
      (gamma-butyrolactones) containing two, four, or six deuterium atoms has been
      developed. The labeled dihydro-2(3H)furanones were synthesized in quantitative
      yield from the saturated diacid C4 (succinic) or unsaturated diacids C4 (fumaric,
      maleic, or acetylendicarboxylic) in the presence of Ru4H4(CO)8(PBu3)4 using a
      deuterium pressure of 180 bar at 180 degrees C. This methodology was applied to
      the total synthesis of a hexadeuterated matairesinol lignan: The 3,4-bis[[3
      methoxy-4-(phenylmethoxy)phenyl]methyl]dihydro-2(3H)furanone-[7,7',8,8',9',9'-D6]
      (benzyl-protected matairesinol-D6) was fully characterized.

PMID- 17447795
TI  - Genotoxic mechanisms of asbestos fibers: role of extranuclear targets.
AB  - Asbestos fibers are carcinogenic to both humans and experimental animals. The
      continued discoveries of exposure routes whereby the general public is exposed to
      asbestos suggest a long-term, low-dose exposure for a large number of people.
      However, the mechanisms by which asbestos induces malignancy are not entirely
      understood. In previous studies, we have shown that asbestos is an effective gene
      and chromosomal mutagen when assayed using the highly sensitive AL mutation assay
      and that the mutagenicity is mediated by reactive oxygen species. The objective
      of the present study is to determine the origin of these radical species,
      particularly reactive nitrogen species, in fiber mutagenesis. Using the radical
      probe 5',6'-chloromethyl-2',7'-dihydroxyphenoxazine diacetate to trap reactive
      radical species, we showed that crocidolite increased the levels of oxyradicals
      in cytoplasts, in the absence of the nucleus, in a dose-dependent manner, which
      was reduced significantly by cotreatment with the radical scavenger dimethyl
      sulfoxide. Treatment of enucleated cells with crocidolite asbestos followed by
      rescue fusion using karyoplasts from control cells resulted in significant mutant
      induction, indicating that the nuclear-cytoplasmic interaction is necessary for
      fiber mutagenesis. Using the fluorescent probe 2,3-diaminonaphthotriazole,
      crocidolite fibers were shown to induce a dose-dependent increase of nitric oxide
      production, which was suppressed significantly by concurrent treatment with the
      nitric oxide synthase inhibitor, NG-methyl-L-arginine (L-NMMA). Similarly, there
      was a dose-dependent decrease in the mutation yield induced by crocidolites in
      the presence of graded doses of L-NMMA. These data showed that extranuclear
      targets play an essential role in the initiation of oxidative damage that
      mediates fiber mutagenesis in mammalian cells.

PMID- 17447796
TI  - Development and evaluation of an electrochemical method for studying reactive
      phase-I metabolites: correlation to in vitro drug metabolism.
AB  - A reactive metabolite may react covalently with proteins or DNA to form adducts
      that ultimately may lead to a toxic response. Reactive metabolites can be formed
      via, for example, cytochrome P450-mediated phase 1 reactions, and in this study,
      we report the development and evaluation of an electrochemical method for
      generating reactive metabolites. Paracetamol was used as a test compound to
      develop the method. The stability of the electrochemically generated N-acetyl-p
      benzoquinoneimine (NAPQI) from paracetamol was investigated at 37 degrees C at pH
      5.0, 7.4, and 9.0. The highest stability of NAPQI was observed at pH 7.4. The
      reaction rate between NAPQI and glutathione (GSH) was studied with cyclic
      voltammetry. NAPQI reacted quantitatively with GSH within 130 ms. The reactivity
      of NAPQI toward other nucleophiles was investigated, and for the reaction with N
      acetyltyrosine, a time-dependent formation of a conjugate with N-acetyltyrosine
      was observed from 0 to 4 min. The applicability of the method was evaluated with
      compounds that were able to form quinone imines (amodiaquine), quinones (3-tert
      butyl-4-hydroxyanisole and p-cresol), imine methides (3-methylindole;
      trimethoprim), quinone methides (3,5-di-tert-butyl-4-hydroxytoluene), and
      nitrenium ions (clozapine). The compounds were oxidized in an analytical
      electrochemical cell, and the formed reactive metabolites were trapped with GSH.
      The samples were then analyzed by LC-MS and LC-MS/MS. For comparison, all
      compounds were incubated with GSH in rat and human liver microsomes, and the
      formation of GSH conjugates was compared with that observed by electrochemical
      oxidation. Furthermore, the electrochemical method was used to synthesize a GSH
      conjugate of clozapine, which made it possible to obtain structural information
      by NMR. In summary, a high degree of similarity was observed between the
      conjugates identified from electrochemical oxidation and GSH conjugates
      identified from incubation with liver microsomes. In conclusion, we have
      developed a method that is useful for studies on reactive metabolites and
      furthermore can be scaled up for the synthesis of GSH conjugates for NMR.

PMID- 17447797
TI  - DNA-based approach for interparticle interaction control.
AB  - Micron-sized latex particles with single-stranded DNA grafted to the surface have
      been used as a model system to study DNA mediated interactions. A new approach of
      tuning the interactions between particles is proposed, which allows for a gradual
      change of the assembly rate for fixed physical conditions of a solution by
      combining hybridizing "linker" DNA with nonhybridizing "neutral" DNA. The effect
      of linker/neutral DNA ratios on particle assembly kinetics and aggregate
      morphology has been experimentally investigated for a range of ionic strengths.
      The conditions for controlling various assembly morphologies have been
      identified, and the involved attractive and repulsive interactions have been
      described and explained for the proposed approach. The calculated attractive
      repulsive behavior is in good agreement with experimental results. The described
      approach provides general perspectives for further fine-tuning DNA-mediated
      assembly systems.

PMID- 17447798
TI  - Evidence for a reverse U-shaped conformation of single-chain bolaamphiphiles at
      the air-water interface.
AB  - Infrared reflection absorption spectroscopy and X-ray reflectivity have been used
      to elucidate the molecular orientation and hydrocarbon chain conformation and
      packing of the symmetric long-chain bolaamphiphiles dotriacontane-1,1'-diyl-bis
      [2-(trimethylammonio)ethylphosphate] (PC-C32-PC) and dotriacontane-1,1'-diyl-bis
      [2-(dimethylammonio)ethylphosphate] (Me2PE-C32-Me2PE) at the air-water interface.
      At low surface pressures, these bipolar amphiphiles are found to lie flat on the
      water surface with a disordered chain. With increasing surface pressure, the
      alkyl chain becomes more ordered. Concomitantly, the chain is bent pointing into
      the air, whereas both polar headgroups keep contact with the water subphase. At
      an area of 0.9-1.1 nm2 per molecule, a surface pressure plateau is reached for
      both bolaamphiphiles, where the molecules adopt a reverse U-shaped conformation
      with a strongly tilted alkyl chain. Further compression leads to the formation of
      3-D aggregates.

PMID- 17447799
TI  - Functionalizable Nanomorphology Gradients via Colloidal Self-Assembly.
AB  - We present a novel approach for the fabrication of tailored nanomorphology
      gradients on metal oxide surfaces. We first show the direct formation of a
      nanocolloidal density gradient by a dip-coating process. The obtained silica
      nanoparticle gradients are then subjected to a heat treatment. Control of this
      sintering step allows the precise tailoring of the particle morphology on the
      surface. Both these processes together provide a new tool to form precise,
      tunable, and material-independent nanomorphology gradients.

PMID- 17447800
TI  - Attachment and phospholipase A2-induced lysis of phospholipid bilayer vesicles to
      plasma-polymerized maleic anhydride/SiO2 multilayers.
AB  - This article describes a method by which intact vesicles can be chemically
      attached to hydrolyzed maleic anhydride films covalently bound to plasma
      polymerized SiO2 on Au substrates. Surface plasmon field-enhanced fluorescence
      spectroscopy (SPFS) combined with surface plasmon resonance spectroscopy (SPR)
      was used to monitor the activation of plasma-deposited maleic anhydride (pp-MA)
      film with EDC/NHS and the subsequent coupling of lipid vesicles. The vesicles
      were formed from a mixture of phosphatidylcholine and phosphatidylethanolamine
      lipids, with a water-soluble fluorophore encapsulated within. Vesicle attachment
      was measured in real time on plasma films formed under different pulse conditions
      (plasma duty cycle). Optimum vesicle attachment was observed on the pp-MA films
      containing the highest density of maleic anhydride groups. Phospholipase A2 was
      used to lyse the surface-bound vesicles and to release the encapsulated
      fluorophore.

PMID- 17447801
TI  - Facile chemical approach to ZnO submicrometer particles with controllable
      morphologies.
AB  - We have developed a simple wet-chemistry approach to fabricating ZnO
      submicrometer particles with unique morphologies including rings, bowls,
      hemispheres, and disks. The size and morphology of the particles can be
      conveniently tailored by varying the concentrations of the zinc precursor. The
      reaction temperature, pH, and concentration of ammonia are also found to play
      critical roles in directing the formation of these particle morphologies. These
      submicrometer particles exhibit strong white-light emission upon UV excitation as
      a result of the presence of surface defect states resulting from the fabrication
      method and synthesis conditions.

PMID- 17447802
TI  - Directed disassembly of an interfacial rubisco protein network.
AB  - We present the first study of the directed disassembly of a protein network at
      the air-water interface by the synergistic action of a surfactant and an enzyme.
      We seek to understand the fundamentals of protein network disassembly by using
      rubisco adsorbed at the air-water interface as a model. We propose that rubisco
      adsorption at the air-water interface results in the formation of a fishnet-like
      network of interconnected protein molecules, capable of transmitting lateral
      force. The mechanical properties of the rubisco network during assembly and
      disassembly at the air-water interface were characterized by direct measurement
      of laterally transmitted force through the protein network using the Cambridge
      interfacial tensiometer. We have shown that, when used individually, either 2 ppm
      of the surfactant, sodium dodecyl benzyl sulfonate (SDOBS), or 2 ppm of the
      enzyme, subtilisin A (SA), were insufficient to completely disassemble the
      rubisco network within 1 h of treatment. However, a combination of 2 ppm SDOBS
      and 2 ppm SA led to almost complete disassembly within 1 h. Increasing the
      concentration of SA in the mixture from 2 to 10 ppm, while keeping the SDOBS
      concentration constant, significantly decreased the time required to completely
      disassemble the rubisco network. Furthermore, the initial rate of network
      disassembly using formulations containing SDOBS was surprisingly insensitive to
      this increase in SA concentration. This study gives insight into the role of
      lateral interactions between protein molecules at interfaces in stabilizing
      interfacial protein networks and shows that surfactant and enzyme working in
      combination proves more effective at disrupting and mobilizing the interfacial
      protein network than the action of either agent alone.

PMID- 17447803
TI  - Spectroelectrochemical examination of the interaction between bacterial cells and
      gold electrodes.
AB  - The interaction between bacterial cells of Pseudomonas fluorescens (ATCC 17552)
      and gold electrodes was analyzed by cyclic voltammetry (CV) and attenuated total
      reflection-surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS). The
      voltammetric evaluation of cell adsorption showed a decrease in the double-layer
      capacitance of polyoriented single-crystal gold electrodes with cell adhesion. As
      followed by IR spectroscopy in the ATR configuration, the adsorption of bacterial
      cells onto thin-film gold electrodes was mainly indicated by the increase in
      intensity with time of amide I and amide II protein-related bands at 1664 and
      1549 cm(-1), respectively. Bands at 1448 and 2900 cm(-1) corresponding to the
      scissoring and the stretching bands of CH2 were also detected, together with a
      minor peak at 1407 cm(-1) due to the vs COO- stretching. Weak signals at 1237 cm(
      1) were due to amide III, and a broad band between 1100 and 1200 cm(-1) indicated
      the presence of alcohol groups. Bacteria were found to displace water molecules
      and anions coadsorbed on the surface in order to interact with the electrode
      intimately. This fact was evidenced in the SEIRAS spectra by the negative
      features appearing at 3450 and 3575 cm-1, corresponding to interfacial water
      directly interacting with the electrode and water associated with chloride ions
      adsorbed on the electrode, respectively. Experiments in deuterated water
      confirmed these assignments and allowed a better estimation of amide absorption
      bands. In CV experiments, an oxidation process was observed at potentials higher
      than 0.4 V that was dependent on the exposure time of electrodes in concentrated
      bacterial suspensions. Adsorbed bacterial cells were found to get closer to the
      gold surface during oxidation, as indicated by the concomitant increment in the
      main IR bacterial signals including amide I, a sharp band at 1240 cm(-1), and a
      broad one at 1120 cm(-1) related to phosphate groups in the bacterial membranes.
      It is proposed to be due to the oxidation of lipopolysaccharides on the outermost
      bacterial surface.

PMID- 17447804
TI  - Identification of protein components in in vivo human acquired enamel pellicle
      using LC-ESI-MS/MS.
AB  - The acquired enamel pellicle is a thin protein film forming upon exposure of
      tooth enamel surfaces to saliva. The structural analysis of this integument
      relies on efficient pellicle harvesting and protein identification procedures.
      Material from three individual subjects and two pooled samples yielded the
      identification by LC-ESI-MS/MS of 130 pellicle proteins of which 89 were found in
      three or more experiments. A high intersubject consistency in pellicle
      composition was observed.

PMID- 17447805
TI  - Liquid mixtures of xenon with fluorinated species: xenon + sulfur hexafluoride.
AB  - The vapor-liquid equilibrium of binary mixtures of xenon + SF6 has been measured
      at nine temperatures from 235.34 to 295.79 K and pressures up to 6.5 MPa. The
      mixture critical line is found to be continuous between the critical points of
      the pure components, and hence, the system can be classified as type I phase
      behavior in the scheme of van Konynenburg and Scott. The excess Gibbs free
      energies have been calculated, and the experimental results have been interpreted
      using the statistical associating fluid theory for potentials of variable range
      (SAFT-VR). Additionally, the SAFT-VR equation has been used to model other
      systems involving SF6 and alkanes, illustrating the predictability of the
      approach and further demonstrating the transferability of parameters between
      binary mixtures involving alkanes and xenon.

PMID- 17447806
TI  - Influence of acrylate arm topology on phase diagrams of mixtures of multiarm
      acrylate photocurative monomers and nematic liquid crystals.
AB  - Phase equilibria of binary mixtures of liquid crystal and multiarm star acrylate
      derivatives have been established as a function of the number of acrylate arms by
      means of cloud point determination. Equilibrium phase diagrams of liquid
      crystal/multiarm acrylate derivatives have been calculated self-consistently in
      the framework of combined Flory-Huggins free energy of liquid-liquid demixing and
      Maier-Saupe free energy of nematic ordering. It was found experimentally that the
      phase diagram of the branched/star molecule/solvent shifts to elevated
      temperatures with an increasing number of acrylate arms. This movement of the
      coexistence line is attributed to the architectural effect contributing to the
      athermal entropic part of the chi interaction parameter. The present self
      consistent solution has been tested satisfactorily with the observed phase
      diagrams of liquid crystal/acrylate systems.

PMID- 17447808
TI  - Determination of redox potentials for the Watson-Crick base pairs, DNA
      nucleosides, and relevant nucleoside analogues.
AB  - Redox potentials for the DNA nucleobases and nucleosides, various relevant
      nucleoside analogues, Watson-Crick base pairs, and seven organic dyes are
      presented based on DFT/B3LYP/6-31++G(d,p) and B3YLP/6-311+G(2df,p)//B3LYP/6-31+G*
      levels of calculations. The values are determined from an experimentally
      calibrated set of equations that correlate the vertical ionization (electron
      affinity) energy of 20 organic molecules with their experimental reversible
      oxidation (reduction) potential. Our results are in good agreement with those
      estimated experimentally for the DNA nucleosides in acetonitrile solutions
      (Seidel et al. J. Phys. Chem. 1996, 100, 5541). We have found that nucleosides
      with anti conformation exhibit lower oxidation potentials than the corresponding
      syn conformers. The lowering in the oxidation potential is due to the formation
      of an intramolecular hydrogen bonding interaction between the 5'-OH group of the
      sugar and the N3 of the purine bases or C2=O of the pyrimidine bases in the syn
      conformation. Pairing of adenine or guanine with its complementary pyrimidine
      base decreases its oxidation potential by 0.15 or 0.28 V, respectively. The
      calculated energy difference between the oxidation potential for the G.C base
      pair and that of the guanine base is in good agreement with the experimental
      value estimated recently (0.34 V: Caruso, T.; et al. J. Am. Chem. Soc. 2005, 127,
      15040). The complete and consistent set of reversible redox values determined in
      this work for the DNA constituents is expected to be of considerable value to
      those studying charge and electronic energy transfer in DNA.

PMID- 17447807
TI  - Preferential solvation in urea solutions at different concentrations: properties
      from simulation studies.
AB  - We performed molecular dynamics simulations of urea solutions at different
      concentrations with two urea models (OPLS and KBFF) to examine the structures
      responsible for the thermodynamic solution properties. Our simulation results
      showed that hydrogen-bonding properties such as the average number of hydrogen
      bonds and their lifetime distributions were nearly constant at all concentrations
      between infinite dilution and the solubility limit. This implies that the
      characterization of urea-water solutions in the molarity concentration scale as
      nearly ideal is a result of facile local hydrogen bonding rather than a global
      property. Thus, urea concentration does not influence the local propensity for
      hydrogen bonds, only how they are satisfied. By comparison, the KBFF model of
      urea donated fewer hydrogen bonds than OPLS. We found that the KBFF urea model in
      TIP3P water better reproduced the experimental density and diffusion constant
      data. Preferential solvation analysis showed that there were weak urea-urea and
      water-water associations in OPLS solution at short distances, but there were no
      strong associations. We divided urea molecules into large, medium, and small
      clusters to examine fluctuation properties and found that any particular urea
      molecule did not stay in the same cluster for a long time. We found neither
      persistent nor large clusters.

PMID- 17447809
TI  - Car-Parrinello molecular dynamics study of anharmonic systems: a Mannich base in
      solution.
AB  - A Car-Parrinello molecular dynamics study was performed for 4,5-dimethyl-2-(N,N
      dimethylaminomethyl)phenol, a Mannich base, to investigate the vibrational
      properties in solution of its intramolecular hydrogen bond. The dynamic behavior
      of this hydrogen-bonded system was investigated using an explicit solvent model.
      Addition of a nonpolar solvent permitted inclusion of delicate environmental
      effects on the strongly anharmonic system which was studied from first
      principles. Molecular dynamics and a posteriori quantization of the O-H motion
      were applied to reproduce the vibrational features of the O-H stretching mode.
      Consistent application of Car-Parrinello dynamics based on the density functional
      theory with subsequent solution of the vibrational Schrodinger equation for the O
      H stretching motion offers an effective method for strongly anharmonic systems,
      and this is supported by the comparison of the results with experimental spectra.
      As a further element of the intramolecular hydrogen bond study, the effects of
      deuteration were taken into account and a successful application of the O-H
      stretching mode quantization technique to the liquid phase is demonstrated. This
      provides a valuable computational methodology for investigations incorporating
      nuclear quantum effects in the liquid phase and enzyme active centers and can be
      used to investigate numerous systems that are not readily susceptible to
      experimental analysis.

PMID- 17447810
TI  - Inverse temperature-dependent pathway of cellulose decrystallization in
      trifluoroacetic acid.
AB  - An unusual inverse temperature-dependent pathway was observed during cellulose
      decrystallization in trifluoroacetic acid (TFA). Decreasing the TFA treatment
      temperature accelerated the cellulose decrystallization process. It took only 100
      min to completely decrystallize cellulose at 0 degrees C in TFA, a result not
      achieved in 48 h at 25 degrees C in the same medium. There was neither cellulose
      esterification nor a change of cellulose macrofibril morphology by TFA treatment
      at 0 degrees C. Our IR data suggest that TFA molecules are present as cyclic
      dimers when they penetrate into crystalline cellulose regions, transforming
      crystalline cellulose to amorphous cellulose. On the other hand, the rate of TFA
      penetration into the cellulose matrix was greatly retarded at higher temperatures
      where monomeric TFA prevails. At elevated temperatures, esterification of TFA
      monomers on the external surface of crystalline cellulose, agglomeration of
      cellulose macrofibrils, as well as water released from the esterification
      reaction, inhibit the diffusion rate of TFA into the cellulose crystalline region
      and decrease the TFA swelling capability.

PMID- 17447811
TI  - Short-range order in liquid aluminum chloride: ab initio molecular dynamics
      simulations and quantum-chemical calculations.
AB  - We use ab initio molecular dynamics simulations based on density-functional
      theory and quantum-chemistry calculations on molecular clusters to examine the
      structure of liquid AlCl3. In the past, conflicting descriptions of the short
      range-order in molten AlCl3, based on either edge-sharing dimers or corner
      sharing oligomers, have been proposed. This liquid also poses a simulation
      challenge, due to the possibility of ring-like trimers which can be metastable on
      the order of >10 ps. Simulations which begin with monomers, either random or
      ordered, appear to be able to produce proper ratios of ring-trimer to dimer-plus
      tail molecular structures without the need to achieve long-time scale chemical
      equilibrium. Single-molecule calculations lend further support to the conclusion
      that the liquid is composed largely of edge-sharing dimers.

PMID- 17447812
TI  - Kinetics of formation and dissociation of aquocobalt(III) complexes with some
      carboxylic acids in acid perchlorate solution.
AB  - The rates of formation and dissociation of monocarboxylic complexes of
      aquocobalt(III) cations with propionic, malonic, and 2-ethylmalonic acids have
      been measured with the stopped-flow method over a range of concentrations and
      temperatures in acid perchlorate media at an ionic strength 3.0 M. Although the
      rate constants for reactions of CoOHaq2+ with neutral ligands cover only a small
      range, indicating a dissociative mechanism, the associated activation parameters
      change cooperatively. These variations are discussed in terms of differences in
      the structure, proton distribution, and rates of water loss in the ion-pair
      precursors for the different ligands. Similar activation enthalpies of
      dissociation indicate a common mode of coordination, and the positive activation
      entropies for dissociation are consistent with a neutral leaving group.

PMID- 17447813
TI  - Tandem Pd(II)-catalyzed vinyl ether exchange-Claisen rearrangement as a facile
      approach to gamma,delta-unsaturated aldehydes.
AB  - A sequential allyl vinyl ether formation-Claisen rearrangement process catalyzed
      by a palladium(II)-phenanthroline complex is reported. The effects of allylic
      alcohol structure, type of vinylating agent, and palladium catalysts are
      discussed. This method provides a convenient approach to gamma,delta-unsaturated
      aldehydes under mild conditions that avoid the use of toxic Hg(II) catalysts. The
      new methodology has been successfully demonstrated on the kilogram scale.

PMID- 17447814
TI  - Evaluation of the binding ability of a novel dioxatetraazamacrocyclic receptor
      that contains two phenanthroline units: selective uptake of carboxylate anions.
AB  - The novel dioxatetraaza macrocycle [26]phen2N4O2, which incorporates two
      phenanthroline units, has been synthesized, and its acid-base behavior has been
      evaluated by potentiometric and 1H NMR methods. Six protonation constants were
      determined, and the protonation sequence was established by NMR. The location of
      the fifth proton on the phen nitrogen was confirmed by X-ray determinations of
      the crystal structures of the receptor as bromide and chloride salts. The two
      compounds have the general molecular formula {(H5[26]phen2N4O2)Xn(H2O)(5-n)}X(n
      1) x mH2O, where X = Cl, n = 3, and m = 6 or X = Br, n = 4, and m = 5.5. In the
      solid state, the (H5[26]phen2N4O2)(5+) cation adopts a "horseshoe" topology with
      sufficient room to encapsulate three or four halogen anions through the several N
      H...X hydrogen-bonding interactions. Two supermolecules
      {(H5[26]phen2N4O2)Xn(H2O)5-n}(5-n)(+) form an interpenetrating dimeric species,
      which was also found by ESI mass spectrum. Binding studies of the protonated
      macrocycle with aliphatic (ox(2-), mal(2-), suc(2-), cit(3-), cta(3-)) and
      aromatic (bzc(-), naphc(-), anthc(-), pyrc(-), ph(2-), iph(2-), tph(2-), btc(3-))
      anions were determined in water by potentiometric methods. These studies were
      complemented by 1H NMR titrations in D2O of the receptor with selected anions.
      The Hi[26]phen2N4O2(i+) receptor can selectively uptake highly charged or
      extended aromatic carboxylate anions, such as btc(3-) and pyrc(-), in the pH
      ranges of 4.0-8.5 and <4.0, respectively, from aqueous solution that contain the
      remaining anions as pollutants or contaminants. To obtain further insight into
      these structural and experimental findings, molecular dynamics (MD) simulations
      were carried out in water solution.

PMID- 17447815
TI  - Enantioselective synthesis of (+)-majusculone.
AB  - The first enantioselective synthesis of a chamigrane sesquiterpene, (+)
      majusculone, has been completed. The quaternary center was generated
      asymmetrically by alkylidene carbene insertion, with retention of absolute
      configuration, from a diastereomerically pure ketal.

PMID- 17447816
TI  - Synthesis and determination of the absolute configuration of chiral
      tetracosanaphthalenes.
AB  - Tetracosanaphthalenes with diethylaminocarbonylmethoxy side chains were
      constructed by bottom-up synthesis, and their absolute configurations were
      determined by an exciton chirality method.

PMID- 17447817
TI  - A versatile strategy for the synthesis of 2,6-disubstituted dihydropyranones.
AB  - A concise synthesis of 2,6-disubstituted dihydropyranones was developed. This
      sequence is based on the Smith three-component dithiane linchpin coupling
      strategy. By simply switching the order of epoxide addition in the linchpin
      coupling step, two analogous dihydropyranones were prepared in good yield from
      the same starting materials. This sequence allows for considerable flexibility in
      the nature of R(1) and R(2) groups, which facilitates the preparation of a
      diverse array of 2,6-disubstituted dihydropyranones.

PMID- 17447818
TI  - Hetero Diels-Alder synthesis of 3-hydroxypyridines: access to the nosiheptide
      core.
AB  - The 1-azadiene hetero Diels-Alder reaction of silylated enol oximes with alkynes
      was investigated and was optimized to furnish 2,5,6-trisubstituted 3
      hydroxypyridines in high yields in one simple operation. Importantly,
      monosubstituted alkynyl ketones were found to lead to the formation of the 6
      isomer with exceptional regioselectivity (>95:5). This methodology was applied to
      a scaleable synthesis of the core structure of the potent antibiotic nosiheptide.
      Protecting groups were optimized, which led to a racemization-free seven-step
      synthesis of the key building block.

PMID- 17447819
TI  - A joint experimental and theoretical study of the palladium-catalyzed
      electrophilic allylation of aldehydes.
AB  - Palladium-catalyzed electrophilic allylation of aldehydes with allylstannanes has
      been proposed in the literature as a model reaction illustrating the potential of
      nucleophilic eta(1)-allyl palladium pincer complexes to promote new catalytic
      processes. This reaction was studied by a joint experimental and theoretical
      approach. It was shown that pincer palladium complexes featuring a S
      approximately P approximately S and a S approximately C approximately S
      tridentate ligand are efficient catalysts for this reaction. The full mechanism
      of this transformation was studied in detail by means of DFT calculations. Two
      pathways were explored: the commonly proposed mechanism involving eta(1)-allyl
      palladium intermediates and a Lewis acid promoted mechanism. Both of these
      mechanisms were compared to the direct transformation that was shown
      experimentally to occur under mild conditions. The mechanism involving an eta(1)
      allyl palladium intermediate has been discarded on energetic grounds, the
      nucleophilic attack and the transmetalation step being more energetically
      demanding than the direct reaction between allyltin and the aldehyde. On the
      other hand, a mechanism where the palladium acts as a Lewis acid proved to be
      fully consistent with all experimental and theoretical results. This mechanism
      involves (L approximately X approximately L)Pd(+) species which activate the
      aldehyde moiety toward nucleophilic attack.

PMID- 17447820
TI  - Efficient NO equivalent for activation of molecular oxygen and its applications
      in transition-metal-free catalytic aerobic alcohol oxidation.
AB  - tert-Butyl nitrite (TBN) was identified as an efficient NO equivalent for the
      activation of molecular oxygen. The unique property of TBN enabled TEMPO
      catalyzed aerobic alcohol oxidation to be performed in high-volume efficiency. Up
      to a 16,000 turnover number was achieved in this transition-metal-free aerobic
      catalytic system. Under the optimal reaction conditions, various alcohols were
      converted into their corresponding carbonyl compounds with TEMPO/HBr/TBN as
      catalyst. The newly developed method was suitable for the oxidation of solid
      substrate alcohols with high melting point and/or low solubility under the help
      of minimum solvent to form a slurry.

PMID- 17447821
TI  - Making plastics from carbon dioxide: salen metal complexes as catalysts for the
      production of polycarbonates from epoxides and CO2.

PMID- 17447822
TI  - Friction dependence on alpha-relaxations in a tethered polymer monolayer.
AB  - Functionalized low-molecular-weight polyisoputylene is commonly used as a
      lubricant additive to control low-velocity friction in clutches. The friction of
      tethered monolayers as a function of temperature and velocity was examined using
      lateral force microscopy. The friction force was found to obey time-temperature
      superposition, which indicates that the friction originates from a single
      relaxation mode. The scaling factors are identical to those obtained from neutron
      spin echo experiments of alpha-relaxations, linking the friction directly to
      segmental motion.

PMID- 17447823
TI  - Simultaneous self-assembly, orientation, and patterning of peptide-amphiphile
      nanofibers by soft lithography.
AB  - Self-assembled nanofibers of peptide-amphiphile molecules have been of great
      interest because of their bioactivity both in vitro and in vivo. In this work, we
      demonstrate the simultaneous self-assembly, alignment, and patterning of these
      nanofibers over large areas by a novel technique termed sonication-assisted
      solution embossing. In this soft lithographic technique, the nanostructures self
      assemble by solvent evaporation while under the influence of ultrasonic agitation
      and confinement within the topographical features of an elastomeric stamp. The
      nanofibers orient parallel to the channels as they assemble out of solution,
      yielding bundles of aligned nanofibers on the substrate after the stamp is
      removed. Alignment is likely a result of steric confinement and possibly a
      transition to a lyotropic liquid crystalline phase as solvent evaporates. This
      technique is not limited to uniaxial alignment and is shown to be able to guide
      nanofibers around turns. Alignment of nanostructures by this method introduces
      the possibility of controlling macroscale cellular behavior or material
      properties by tuning the directionality of interactions at the nanoscale.

PMID- 17447824
TI  - Nanoscale roughness on metal surfaces can increase tip-enhanced Raman scattering
      by an order of magnitude.
AB  - We studied the influence of nanosteps on signal intensity in gap-mode tip
      enhanced Raman spectroscopy (TERS). A benzenethiol monolayer adsorbed on an Au
      substrate was investigated. The correlation between the TERS signal and the local
      topography on the substrate shows that a 2 nm high sharp step on the Au surface
      can significantly increase the enhancement. Furthermore, theoretical models were
      built, and the numerical simulation results were consistent with our experimental
      results. The findings provide evidence that nanoscale roughness can play a
      crucial role in the "hot sites" corresponding to single-molecule surface-enhanced
      Raman spectroscopy (SERS).

PMID- 17447825
TI  - Bacterial meningitis: the impact of vaccination.
AB  - Acute bacterial meningitis remains an important cause of morbidity and mortality
      in children. Children <2 years of age are particularly susceptible to infection
      with encapsulated bacteria due to their immature response to polysaccharide
      antigens. Conjugate vaccines, which induce T cell memory, can provide
      immunological protection for these children. The Haemophilus influenzae type b
      (Hib) conjugate vaccine was the first such vaccine to become available. The
      efficacy of the vaccine has been quoted as being 98%. Its introduction was
      followed by a dramatic decrease in the incidence of all invasive Hib disease,
      including meningitis. This reduction was in part due to the ability of these
      vaccines to reduce nasopharyngeal carriage of the organism and thereby induce
      herd immunity. Different Hib vaccines use a variety of protein carriers and
      differ in their immunogenicity and efficacy. The most suitable vaccine needs to
      be determined according to the local epidemiology of Hib disease. Commercial
      combination vaccines may lead to lower antibody levels. A recent increase in the
      incidence of Hib disease in the UK highlights the importance of continued
      surveillance and the need for booster vaccinations to ensure continued
      protection. Conjugate vaccines to Streptococcus pneumoniae and Neisseria
      meningitidis have been developed. The introduction of a pneumococcal conjugate
      vaccine in the US has led to a decrease in the rate of infection by nearly 60% in
      children <5 years of age. A reduction in pneumococcal carriage may also modify
      disease epidemiology. The UK introduced the conjugate meningococcal C vaccine
      into its infant schedule with a corresponding reduction in N. meningitidis group
      C disease. A recent decrease in the effectiveness of the vaccine, however,
      suggests a booster may be necessary in the future. Our present understanding of
      the immunology of conjugate vaccines is far from complete. Developed countries
      have introduced conjugate vaccines into their immunisation schedules to prevent
      bacterial meningitis; however, their high cost precludes their use in many
      developing countries. Progress needs to be made in order to get these highly
      effective vaccines to those areas that need them.

PMID- 17447826
TI  - Atypical antipsychotics for the treatment of bipolar disorder: more shadows than
      lights.
AB  - Atypical antipsychotics are utilised more frequently for the treatment of bipolar
      disorder than first-generation antipsychotics because of their improved
      neurological tolerability. Furthermore, recent studies suggest that psychiatric
      outcomes are improved in patients treated with atypical agents. The aim of this
      article is to review the studies evaluating the effectiveness of atypical
      antipsychotics in treating acute bipolar episodes (bipolar mania, bipolar
      depression and mixed episodes), as well as those investigating the effectiveness
      of atypical antipsychotics as maintenance treatment for the disorder. Because of
      several relevant methodological limitations affecting the vast majority of
      clinical trials, evidence-based information about the effectiveness of atypical
      antipsychotics in treating bipolar disorder is somewhat discouraging. Moreover,
      data indicating effectiveness in managing the acute manic phase and in long-term
      maintenance treatment are quantitatively robust only for olanzapine. However,
      olanzapine seems to have no advantages in terms of tolerability and therapy
      compliance when compared with classical mood stabilisers or first-generation
      antipsychotics. In addition, only a few studies have investigated the efficacy of
      atypical antipsychotics for treating bipolar depression. Hence, information
      regarding the effectiveness of such medications in treating this specific phase
      of bipolar disorder should be considered as still preliminary. Given this
      situation, further independent and well-designed studies are urgently needed
      before definitive conclusions on the effectiveness of most atypical
      antipsychotics in the different clinical situations characterising the natural
      course of bipolar disorder can be drawn.

PMID- 17447827
TI  - Use of non-benzodiazepine hypnotics in the elderly: are all agents the same?
AB  - Sleep disorders, especially insomnia, are common in older adults. These disorders
      are frequently treated using non-benzodiazepine hypnotics. Nonetheless, there is
      a relative lack of data regarding the use of these agents in the elderly, and
      whether any of these medications is superior to any other in the class when used
      in the elderly is also unclear. In this article, we review, by way of the
      published literature, the pharmacodynamics, pharmacokinetics, drug interactions,
      efficacy and safety of zolpidem, zaleplon, zopiclone, eszopiclone and ramelteon
      in the elderly. Special emphasis is placed on identifying relevant differences
      between these medications when used in older adults with insomnia. Based
      primarily on data from placebo-controlled trials, the non-benzodiazepines
      reviewed were found to be most effective at improving sleep latency and sleep
      quality, and least effective at enhancing total sleep time. The efficacy of
      ramelteon was limited to improving sleep latency, while all other agents,
      especially at higher doses, were found to produce improvement in both sleep
      latency and some improvement in total sleep time. All of the medications were
      found to be well tolerated in the elderly. From pharmacokinetic and drug-drug
      interaction perspectives, zaleplon and ramelteon offer the advantage of not being
      primarily metabolised via the cytochrome P450 3A4 isoenzyme. In conclusion, based
      on relatively limited data, zopiclone, zolpidem, zaleplon, eszopiclone and
      ramelteon represent modestly effective and generally well tolerated treatments
      for insomnia in older adults. While some actual and potential differences exist
      among these medications, more comparative trials are needed.

PMID- 17447828
TI  - Effect of adjunctive modafinil on wakefulness and quality of life in patients
      with excessive sleepiness-associated obstructive sleep apnoea/hypopnoea syndrome:
      a 12-month, open-label extension study.
AB  - OBJECTIVE: To evaluate the long-term effect on wakefulness, functional status and
      quality of life and tolerability of adjunctive modafinil in continuous positive
      airway pressure (CPAP)-treated patients with residual excessive sleepiness (ES)
      associated with obstructive sleep apnoea/hypopnoea syndrome (OSA/HS). STUDY
      DESIGN: 12-month, open-label extension of a 12-week, randomised, double-blind,
      placebo-controlled study. SETTING: Thirty-seven centres in the US and four in the
      UK. PATIENTS: Two hundred and sixty-six patients experiencing ES associated with
      OSA/HS who completed at least 8 weeks of the 12-week double-blind study, and who
      received adequate education and intervention efforts to encourage use of nasal
      CPAP (nCPAP). INTERVENTION: Patients receiving nCPAP therapy were administered
      modafinil 200 mg/day during week 1, 300 mg/day during week 2, and then 200, 300
      or 400 mg/day, based on the investigator's assessment of efficacy and
      tolerability, for the remainder of the study. MAIN OUTCOME MEASURES: Assessments
      included the Epworth Sleepiness Scale (ESS), Functional Outcomes of Sleep
      Questionnaire (FOSQ) and Short Form-36 Health Survey (SF-36). RESULTS: One
      hundred and seventy five patients (66%) completed the study. Modafinil maintained
      a significant effect on wakefulness, as shown by improvement in the ESS total
      score at months 3, 6, 9 and 12 compared with baseline (all p < 0.0001). Modafinil
      also improved functional status (FOSQ total score) and general health (SF-36
      mental and physical component scores) at months 6 and 12 compared with baseline
      (all p < 0.05). Modafinil was well tolerated. The most common adverse events
      reported were infection (11.3%), headache (9.4%) and nervousness (9.0%). Serious
      adverse events were reported in 13 patients, with two of these events (mild
      bradycardia and severe syncope, both in the same patient) considered to be
      possibly related to modafinil. There were few clinically meaningful changes in
      clinical laboratory data, vital signs, physical examination findings or ECG
      results. Important changes included significant increase in blood pressure in six
      patients, five of whom had a history of hypertension. CONCLUSIONS: Adjunctive
      modafinil maintained effects on wakefulness and functional outcomes, and improved
      quality of life in patients with OSA/HS experiencing residual ES over a 12-month
      period. Modafinil was well tolerated during long-term therapy.

PMID- 17447829
TI  - Paliperidone extended release.
AB  - Paliperidone extended release (ER) is an atypical antipsychotic that is
      administered orally once daily to provide consistent plasma drug concentrations
      over 24 hours in adult patients with schizophrenia. In four well controlled
      trials, once-daily administration of paliperidone ER 3-12 mg over 6 weeks was
      more effective than placebo in reducing the positive and negative symptoms
      experienced by adult patients with schizophrenia, including elderly individuals
      aged > or =65 years. Patients with schizophrenia treated with paliperidone ER
      achieved greater improvement in clinically relevant measures of personal and
      social functioning and disease severity than those who received placebo. In
      another well controlled trial, paliperidone ER demonstrated superior efficacy to
      placebo in preventing the recurrence of schizophrenia symptoms. In patients who
      experienced a recurrence, time to recurrence was delayed with paliperidone ER
      compared with placebo administration.black triangle Paliperidone ER 3-12 mg/day
      for 6 weeks was generally well tolerated by patients with schizophrenia in
      clinical trials.

PMID- 17447832
TI  - Pramipexole: in restless legs syndrome.
AB  - Pramipexole is an oral, non-ergoline dopamine agonist with selectivity for the
      dopamine D(3) receptor, which was recently approved in the EU and the US for the
      treatment of idiopathic restless legs syndrome (RLS) in adults. In a
      polysomnographic study, pramipexole 0.125, 0.25, 0.50 or 0.75 mg once daily for 3
      weeks significantly reduced from baseline the periodic limb movement index
      compared with placebo (-27 to -53 vs -3). Pramipexole at a median dosage of 0.35
      mg/day for 6 weeks significantly reduced from baseline the mean International RLS
      Study Group rating scale (IRLS) score compared with placebo (-12.4 vs -6.1) and
      produced a significantly higher response ('much improved' or 'very much
      improved') rate (63% vs 33%) according to the Clinical Global Impressions
      Improvement (CGI-I) scale. In a controlled-withdrawal study in which responders
      to pramipexole following 6 months' therapy were randomised to pramipexole or
      placebo for 12 weeks, significantly less pramipexole than placebo recipients
      reached the target event of predefined worsening of symptoms (21% vs 86%).
      Treatment with pramipexole 0.25, 0.50 or 0.75 mg once daily for 12 weeks
      significantly reduced IRLS scores from baseline values (-13 to -14 vs -9) and
      produced significantly higher proportions of CGI-I responders (68-75% vs 51%)
      compared with placebo. Pramipexole was generally well tolerated, with most
      adverse events being transient and of mild to moderate severity.

PMID- 17447836
TI  - The importance of bottlenecks in protein networks: correlation with gene
      essentiality and expression dynamics.
AB  - It has been a long-standing goal in systems biology to find relations between the
      topological properties and functional features of protein networks. However, most
      of the focus in network studies has been on highly connected proteins ("hubs").
      As a complementary notion, it is possible to define bottlenecks as proteins with
      a high betweenness centrality (i.e., network nodes that have many "shortest
      paths" going through them, analogous to major bridges and tunnels on a highway
      map). Bottlenecks are, in fact, key connector proteins with surprising functional
      and dynamic properties. In particular, they are more likely to be essential
      proteins. In fact, in regulatory and other directed networks, betweenness (i.e.,
      "bottleneck-ness") is a much more significant indicator of essentiality than
      degree (i.e., "hub-ness"). Furthermore, bottlenecks correspond to the dynamic
      components of the interaction network-they are significantly less well
      coexpressed with their neighbors than non-bottlenecks, implying that expression
      dynamics is wired into the network topology.

PMID- 17447837
TI  - Regulatory circuit of human microRNA biogenesis.
AB  - miRNAs (microRNAs) are a class of endogenous small RNAs that are thought to
      negatively regulate protein production. Aberrant expression of many miRNAs is
      linked to cancer and other diseases. Little is known about the factors that
      regulate the expression of miRNAs. We have identified numerous regulatory
      elements upstream of miRNA genes that are likely to be essential to the
      transcriptional and posttranscriptional regulation of miRNAs. Newly identified
      regulatory motifs occur frequently and in multiple copies upstream of miRNAs. The
      motifs are highly enriched in G and C nucleotides, in comparison with the
      nucleotide composition of miRNA upstream sequences. Although the motifs were
      predicted using sequences that are upstream of miRNAs, we find that 99% of the
      top-predicted motifs preferentially occur within the first 500 nucleotides
      upstream of the transcription start sites of protein-coding genes; the observed
      preference in location underscores the validity and importance of the motifs
      identified in this study. Our study also raises the possibility that a
      considerable number of well-characterized, disease-associated transcription
      factors (TFs) of protein-coding genes contribute to the abnormal miRNA expression
      in diseases such as cancer. Further analysis of predicted miRNA-protein
      interactions lead us to hypothesize that TFs that include c-Myb, NF-Y, Sp-1, MTF
      1, and AP-2alpha are master-regulators of miRNA expression. Our predictions are a
      solid starting point for the systematic elucidation of the causative basis for
      aberrant expression patterns of disease-related (e.g., cancer) miRNAs. Thus, we
      point out that focused studies of the TFs that regulate miRNAs will be paramount
      in developing cures for miRNA-related diseases. The identification of the miRNA
      regulatory motifs was facilitated by a new computational method, K-Factor. K
      Factor predicts regulatory motifs in a set of functionally related sequences,
      without relying on evolutionary conservation.

PMID- 17447838
TI  - Risk maps for the spread of highly pathogenic avian influenza in poultry.
AB  - Devastating epidemics of highly contagious animal diseases such as avian
      influenza, classical swine fever, and foot-and-mouth disease underline the need
      for improved understanding of the factors promoting the spread of these
      pathogens. Here the authors present a spatial analysis of the between-farm
      transmission of a highly pathogenic H7N7 avian influenza virus that caused a
      large epidemic in The Netherlands in 2003. The authors developed a method to
      estimate key parameters determining the spread of highly transmissible animal
      diseases between farms based on outbreak data. The method allows for the
      identification of high-risk areas for propagating spread in an epidemiologically
      underpinned manner. A central concept is the transmission kernel, which
      determines the probability of pathogen transmission from infected to uninfected
      farms as a function of interfarm distance. The authors show how an estimate of
      the transmission kernel naturally provides estimates of the critical farm density
      and local reproduction numbers, which allows one to evaluate the effectiveness of
      control strategies. For avian influenza, the analyses show that there are two
      poultry-dense areas in The Netherlands where epidemic spread is possible, and in
      which local control measures are unlikely to be able to halt an unfolding
      epidemic. In these regions an epidemic can only be brought to an end by the
      depletion of susceptible farms by infection or massive culling. The analyses
      provide an estimate of the spatial range over which highly pathogenic avian
      influenza viruses spread between farms, and emphasize that control measures aimed
      at controlling such outbreaks need to take into account the local density of
      farms.

PMID- 17447839
TI  - Comprehensive annotation of bidirectional promoters identifies co-regulation
      among breast and ovarian cancer genes.
AB  - A "bidirectional gene pair" comprises two adjacent genes whose transcription
      start sites are neighboring and directed away from each other. The intervening
      regulatory region is called a "bidirectional promoter." These promoters are often
      associated with genes that function in DNA repair, with the potential to
      participate in the development of cancer. No connection between these gene pairs
      and cancer has been previously investigated. Using the database of spliced
      expressed sequence tags (ESTs), we identified the most complete collection of
      human transcripts under the control of bidirectional promoters. A rigorous screen
      of the spliced EST data identified new bidirectional promoters, many of which
      functioned as alternative promoters or regulated novel transcripts. Additionally,
      we show a highly significant enrichment of bidirectional promoters in genes
      implicated in somatic cancer, including a substantial number of genes implicated
      in breast and ovarian cancers. The repeated use of this promoter structure in the
      human genome suggests it could regulate co-expression patterns among groups of
      genes. Using microarray expression data from 79 human tissues, we verify
      regulatory networks among genes controlled by bidirectional promoters. Subsets of
      these promoters contain similar combinations of transcription factor binding
      sites, including evolutionarily conserved ETS factor binding sites in ERBB2,
      FANCD2, and BRCA2. Interpreting the regulation of genes involved in co-expression
      networks, especially those involved in cancer, will be an important step toward
      defining molecular events that may contribute to disease.

PMID- 17447840
TI  - Synergy or independence? Deciphering the interaction of HLA Class I and NK cell
      KIR alleles in early HIV-1 disease progression.

PMID- 17447842
TI  - Novel Crohn disease locus identified by genome-wide association maps to a gene
      desert on 5p13.1 and modulates expression of PTGER4.
AB  - To identify novel susceptibility loci for Crohn disease (CD), we undertook a
      genome-wide association study with more than 300,000 SNPs characterized in 547
      patients and 928 controls. We found three chromosome regions that provided
      evidence of disease association with p-values between 10(-6) and 10(-9). Two of
      these (IL23R on Chromosome 1 and CARD15 on Chromosome 16) correspond to genes
      previously reported to be associated with CD. In addition, a 250-kb region of
      Chromosome 5p13.1 was found to contain multiple markers with strongly suggestive
      evidence of disease association (including four markers with p < 10(-7)). We
      replicated the results for 5p13.1 by studying 1,266 additional CD patients, 559
      additional controls, and 428 trios. Significant evidence of association (p < 4 x
      10(-4)) was found in case/control comparisons with the replication data, while
      associated alleles were over-transmitted to affected offspring (p < 0.05), thus
      confirming that the 5p13.1 locus contributes to CD susceptibility. The CD
      associated 250-kb region was saturated with 111 SNP markers. Haplotype analysis
      supports a complex locus architecture with multiple variants contributing to
      disease susceptibility. The novel 5p13.1 CD locus is contained within a 1.25-Mb
      gene desert. We present evidence that disease-associated alleles correlate with
      quantitative expression levels of the prostaglandin receptor EP4, PTGER4, the
      gene that resides closest to the associated region. Our results identify a major
      new susceptibility locus for CD, and suggest that genetic variants associated
      with disease risk at this locus could modulate cis-acting regulatory elements of
      PTGER4.

PMID- 17447841
TI  - Staphylococcal biofilm exopolysaccharide protects against Caenorhabditis elegans
      immune defenses.
AB  - Staphylococcus epidermidis and Staphylococcus aureus are leading causes of
      hospital-acquired infections that have become increasingly difficult to treat due
      to the prevalence of antibiotic resistance in these organisms. The ability of
      staphylococci to produce biofilm is an important virulence mechanism that allows
      bacteria both to adhere to living and artificial surfaces and to resist host
      immune factors and antibiotics. Here, we show that the icaADBC locus, which
      synthesizes the biofilm-associated polysaccharide intercellular adhesin (PIA) in
      staphylococci, is required for the formation of a lethal S. epidermidis infection
      in the intestine of the model nematode Caenorhabditis elegans. Susceptibility to
      S. epidermidis infection is influenced by mutation of the C. elegans PMK-1 p38
      mitogen-activated protein (MAP) kinase or DAF-2 insulin-signaling pathways. Loss
      of PIA production abrogates nematocidal activity and leads to reduced bacterial
      accumulation in the C. elegans intestine, while overexpression of the icaADBC
      locus in S. aureus augments virulence towards nematodes. PIA-producing S.
      epidermidis has a significant survival advantage over ica-deficient S.
      epidermidis within the intestinal tract of wild-type C. elegans, but not in
      immunocompromised nematodes harboring a loss-of-function mutation in the p38 MAP
      kinase pathway gene sek-1. Moreover, sek-1 and pmk-1 mutants are equally
      sensitive to wild-type and icaADBC-deficient S. epidermidis. These results
      suggest that biofilm exopolysaccharide enhances virulence by playing an
      immunoprotective role during colonization of the C. elegans intestine. These
      studies demonstrate that C. elegans can serve as a simple animal model for
      studying host-pathogen interactions involving staphylococcal biofilm
      exopolysaccharide and suggest that the protective activity of biofilm matrix
      represents an ancient conserved function for resisting predation.

PMID- 17447843
TI  - Conservation of regional gene expression in mouse and human brain.
AB  - Many neurodegenerative diseases have a hallmark regional and cellular pathology.
      Gene expression analysis of healthy tissues may provide clues to the differences
      that distinguish resistant and sensitive tissues and cell types. Comparative
      analysis of gene expression in healthy mouse and human brain provides a framework
      to explore the ability of mice to model diseases of the human brain. It may also
      aid in understanding brain evolution and the basis for higher order cognitive
      abilities. Here we compare gene expression profiles of human motor cortex,
      caudate nucleus, and cerebellum to one another and identify genes that are more
      highly expressed in one region relative to another. We separately perform
      identical analysis on corresponding brain regions from mice. Within each species,
      we find that the different brain regions have distinctly different expression
      profiles. Contrasting between the two species shows that regionally enriched
      genes in one species are generally regionally enriched genes in the other
      species. Thus, even when considering thousands of genes, the expression ratios in
      two regions from one species are significantly correlated with expression ratios
      in the other species. Finally, genes whose expression is higher in one area of
      the brain relative to the other areas, in other words genes with patterned
      expression, tend to have greater conservation of nucleotide sequence than more
      widely expressed genes. Together these observations suggest that region-specific
      genes have been conserved in the mammalian brain at both the sequence and gene
      expression levels. Given the general similarity between patterns of gene
      expression in healthy human and mouse brains, we believe it is reasonable to
      expect a high degree of concordance between microarray phenotypes of human
      neurodegenerative diseases and their mouse models. Finally, these data on very
      divergent species provide context for studies in more closely related species
      that address questions such as the origins of cognitive differences.

PMID- 17447844
TI  - A mammal-specific Doublesex homolog associates with male sex chromatin and is
      required for male meiosis.
AB  - Gametogenesis is a sexually dimorphic process requiring profound differences in
      germ cell differentiation between the sexes. In mammals, the presence of
      heteromorphic sex chromosomes in males creates additional sex-specific
      challenges, including incomplete X and Y pairing during meiotic prophase. This
      triggers formation of a heterochromatin domain, the XY body. The XY body
      disassembles after prophase, but specialized sex chromatin persists, with further
      modification, through meiosis. Here, we investigate the function of DMRT7, a
      mammal-specific protein related to the invertebrate sexual regulators Doublesex
      and MAB-3. We find that DMRT7 preferentially localizes to the XY body in the
      pachytene stage of meiotic prophase and is required for male meiosis. In Dmrt7
      mutants, meiotic pairing and recombination appear normal, and a transcriptionally
      silenced XY body with appropriate chromatin marks is formed, but most germ cells
      undergo apoptosis during pachynema. A minority of mutant cells can progress to
      diplonema, but many of these escaping cells have abnormal sex chromatin lacking
      histone H3K9 di- and trimethylation and heterochromatin protein 1beta
      accumulation, modifications that normally occur between pachynema and diplonema.
      Based on the localization of DMRT7 to the XY body and the sex chromatin defects
      observed in Dmrt7 mutants, we conclude that DMRT7 plays a role in the sex
      chromatin transformation that occurs between pachynema and diplonema. We suggest
      that DMRT7 may help control the transition from meiotic sex chromosome
      inactivation to postmeiotic sex chromatin in males. In addition, because it is
      found in all branches of mammals, but not in other vertebrates, Dmrt7 may shed
      light on evolution of meiosis and of sex chromatin.

PMID- 17447847
TI  - Genetic tests for predicting the toxicity and efficacy of anticancer
      chemotherapy.
AB  - The standard anticancer therapy based "on one size fits all" modality has been
      determined to be ineffective or to be the cause of adverse drug reactions in many
      oncologic patients. Most pharmacogenetic and pharmacogenomic studies so far have
      been focused on toxicity of anticancer drugs such as 6-mercaptopurine,
      thioguanine, irinotecan, methotrexate, 5-fluorouracil (5-FU). Variation in genes
      are known to influence not only toxicity, but also efficacy of chemotherapeutics
      such as platinum analogues, 5-FU and irinotecan. The majority of current
      pharmacogenetic studies focus on single enzyme deficiencies as predictors of drug
      effects; however effects of most anticancer drugs are determined by the interplay
      of several gene products. These effects are polygenic in nature. This review
      briefly describes genetic variations that may impact efficacy and toxicity of
      drugs used in cancer chemotherapy.

PMID- 17447846
TI  - Genetic structure of chimpanzee populations.
AB  - Little is known about the history and population structure of our closest living
      relatives, the chimpanzees, in part because of an extremely poor fossil record.
      To address this, we report the largest genetic study of the chimpanzees to date,
      examining 310 microsatellites in 84 common chimpanzees and bonobos. We infer
      three common chimpanzee populations, which correspond to the previously defined
      labels of "western," "central," and "eastern," and find little evidence of gene
      flow between them. There is tentative evidence for structure within western
      chimpanzees, but we do not detect distinct additional populations. The data also
      provide historical insights, demonstrating that the western chimpanzee population
      diverged first, and that the eastern and central populations are more closely
      related in time.

PMID- 17447845
TI  - Population stratification of a common APOBEC gene deletion polymorphism.
AB  - The APOBEC3 gene family plays a role in innate cellular immunity inhibiting
      retroviral infection, hepatitis B virus propagation, and the retrotransposition
      of endogenous elements. We present a detailed sequence and population genetic
      analysis of a 29.5-kb common human deletion polymorphism that removes the
      APOBEC3B gene. We developed a PCR-based genotyping assay, characterized 1,277
      human diversity samples, and found that the frequency of the deletion allele
      varies significantly among major continental groups (global FST = 0.2843). The
      deletion is rare in Africans and Europeans (frequency of 0.9% and 6%), more
      common in East Asians and Amerindians (36.9% and 57.7%), and almost fixed in
      Oceanic populations (92.9%). Despite a worldwide frequency of 22.5%, analysis of
      data from the International HapMap Project reveals that no single existing tag
      single nucleotide polymorphism may serve as a surrogate for the deletion variant,
      emphasizing that without careful analysis its phenotypic impact may be overlooked
      in association studies. Application of haplotype-based tests for selection
      revealed potential pitfalls in the direct application of existing methods to the
      analysis of genomic structural variation. These data emphasize the importance of
      directly genotyping structural variation in association studies and of accurately
      resolving variant breakpoints before proceeding with more detailed population
      genetic analysis.

PMID- 17447848
TI  - Further characterization of the role of Pso2 in the repair of DNA interstrand
      cross-link-associated double-strand breaks in Saccharomyces cerevisiae.
AB  - DNA interstrand cross-links (ICL) are thought to be one of the most lethal forms
      of DNA damage. Therefore, they present a colossal challenge for the DNA damage
      response and repair pathways. In Saccharomyces cerevisiae, ICL repair utilizes
      factors from all of the three major repair groups: nucleotide excision repair
      (RAD3 epistasis group), post-replication repair (RAD6 epistasis group) and
      recombinational repair (RAD52 epistasis group). Moreover, there are additional
      factors significantly influencing the repair of ICL in this organism. These have
      been designated PSO1-10 based on the psoralen sensitive phenotype of the
      corresponding mutants. Phenotype of the pso2 mutant suggests that Pso2 is not
      involved in incision step of ICL repair, but it rather functions in some
      downstream event such as processing of DNA ends created during generation of ICL
      associated double-strand breaks (DSB). In order to address the question whether
      function of Pso2 in the repair of ICL-associated DSB could be mediated through
      protein-protein interactions, we have conducted a comprehensive two-hybrid screen
      examining a possibility of interaction of Pso2 with Yku70, Yku80, Nej1, Lif1,
      Dnl4, Rad50, Mre11, Xrs2, Rad51, Rad52, Rad54, Rad55, Rad57, Rad59 and Rdh54.
      Here we show that Pso2 associates with none of the above DSB repair proteins,
      suggesting that this protein very likely does not act in the repair of ICL
      associated DSB via crosstalk with DSB repair machinery. Instead, its function in
      this process seems to be rather individual.

PMID- 17447849
TI  - Radiosensitivity of cervical cancer cell lines: the impact of polymorphisms in
      DNA repair genes.
AB  - The aim of this study was to evaluate radiosensitivity of cervical cancer cells
      in vitro and to assess the relationship between genetic polymorphisms in DNA
      repair genes and the response of cells to ionizing radiation. The alkaline comet
      assay as a predictive assay of radiosensitivity was used to examine the
      susceptibility of four human cervical cancer cell lines (CaSki, C-33A, HeLa and
      SiHa) to radiation damages. The initial DNA damage and the residual DNA damage at
      15, 30, 45 and 60 min after irradiation were assessed. Genotypes of DNA repair
      genes (XRCC1, hOGG1, PARP, XPD, XRCC3 and XRCC4) were analyzed by PCR-RFLP
      assays. The comet data clearly indicate a variable but dose-dependent increase in
      the initial DNA damage in all cell lines. The highest slope of dose response
      curve was observed in C-33A cells and this cell line was assumed to be
      radiosensitive. All cell lines repaired DNA damage in a similar manner, the level
      of DNA strand breakage has returned near the background level within 45 min after
      irradiation. According to the genotype we found that C-33A cells are polymorphic
      in the majority of analyzed DNA repair genes. This pilot study indicated
      associations between polymorphisms in DNA repair genes and cell radiosensitivity.

PMID- 17447850
TI  - Flavonoids potentiate the efficacy of cytarabine through modulation of drug
      induced apoptosis.
AB  - Recent studies have provided strong evidence for potential beneficial effects of
      flavonoids in chemoprevention or in combination with chemotherapeutics in tumor
      cells treatment. The aim of this work was to compare the antioxidant properties
      of four flavonoids with emphasis on association of these antioxidant properties
      with their effects on the therapeutic efficacy of cytarabine (AraC) using L1210
      leukemia cells. The results of antiproliferative studies showed that
      antiproliferative potential of flavonoids tested decreased in the order:
      isorhamnetin > kaempferol > myricetin > rutin, while their antioxidant properties
      decreased in the order: rutin > myricetin > kaempferol > isorhamnetin.
      Combinational treatment of isorhamnetin, kaempferol and myricetin with AraC led
      to synergism in their antiproliferative activities (CIs < 1). Rutin exhibited
      antagonism with AraC (CIs > 1). Apoptotic DNA fragmentation and flow cytometry
      analyses revealed that synergism in antiproliferative activities of compounds
      tested might be due to potentiation of AraC-induced apoptosis. In conclusion, our
      results clearly indicate that isorhamnetin, kaempferol and myricetin despite
      their antioxidant properties might be used to increase the sensitivity of
      leukemia cells to AraC treatment.

PMID- 17447851
TI  - Expression of zinc-fingers and homeoboxes 2 in hepatocellular carcinogenesis: a
      tissue microarray and clinicopathological analysis.
AB  - Zinc-fingers and homeoboxes 2 (ZHX2) is a novel transcriptional repressor. ZHX2
      protein expression and its clinicopathological significance in hepatocellular
      carcinoma (HCC) remain largely unknown. The aim of this study was to analyze ZHX2
      protein expression in a range of liver tissues obtained from cholangitis,
      cirrhosis, adjacent non-tumorous tissues, primary HCC tissues, and matched
      metastatic lesions by using Tissue microarray (TMA) technology and compare our
      findings with clinicopathological parameters. ZHX2 protein expression was
      detected only in HCC tissues. ZHX2 expression was associated with clinical stage
      of the disease. The rate of ZHX2 expression was approximately twice as high in
      stage III-IV (31.25%) compared with stage I-II (16.5%). These results
      demonstrated that ZHX2 protein may take part in hepatocellular carcinogenesis and
      HCC progression. In addition, ZHX2 expression in primary lesions with metastasis
      was significantly higher than without metastasis. ZHX2 expression in metastatic
      lesions (45.5%) was as approximately twice as higher than that in primary lesions
      (24.2%) from the same patient. According to these results, ZHX2 was associated
      with metastasis in HCC.

PMID- 17447852
TI  - Incidence of the main genetic markers in glioblastoma multiforme is independent
      of tumor topology.
AB  - Glioblastoma multiforme (GBM) is the most common as well as the most aggressive
      type of primary brain tumor of astrocytic origin in adults. GBM is characterized
      by a high degree of intratumoral heterogeneity both in histomorphology and
      genetic changes. Trisomy/polysomy of chromosome 7, monosomy of chromosome 10,
      EGFR gene amplification and p53 deletion have been described as the typical
      genetic markers for tumor classification and prediction of possible response to
      therapy. Our work was based on detection of these four main genetic changes both
      in central and peripheral parts of the tumors to evaluate possible differences in
      the topological incidence of these genetic markers. Chromosomal abnormalities in
      tumor samples from a group of 21 patients surgically treated for GBM were
      characterized by means of the interphase-fluorescence in situ hybridization (I
      FISH) technique using sets of centromere and locus-specific DNA probes. In
      addition, we performed a detailed analysis of one selected tumor sample using a
      genomic microarray system (GenoSensor Array 300) to characterize copy number
      changes of specific sequences and refine results obtained by I-FISH. However, the
      data show no significant differences in occurrence of the described genetic
      markers in either part of the tumor.

PMID- 17447853
TI  - Carbonyl and oxidative stress in patients with breast cancer--is there a relation
      to the stage of the disease?
AB  - Oxidative and carbonyl stress may, on one hand, contribute to the progression of
      cancer, on the other hand, they may have some antiproliferative effects. We
      examined serum levels of AGEs (advanced glycation end-products), CML
      (carboxymethyllysine) and AOPP (advanced oxidation protein products) in 86
      patients with breast cancer subdivided based on the clinical stage (TNM
      classification), histologic grading, expression of hormonal and C-erb B2
      receptors and in 14 healthy age-matched women as controls. Breast cancer patients
      had higher serum concentrations of AGEs (325,581 +/- 66,037 vs. 271,322 +/-
      34,826 AU, p < 0.01) even in the early stage of the disease; patients with
      advanced breast cancer (stage III and IV) had significantly higher both AGEs and
      AOPP (113.0 +/- 44.9 vs. 78.1 +/- 28.4 micromol/l, p < 0.05) levels, not only
      compared to controls, but also compared to stages I and II. Serum levels of AOPP
      were higher in patients having only weakly positive expression of C-erb 2/Her-neu
      compared to controls and the patients having the highest C-erb2/Her-neu
      expression. Serum concentrations of AGEs in patients with breast cancer
      correlated with the age and also with the serum concentration of AOPP. IN
      CONCLUSION: breast cancer patients had an early increase of AGEs (marker of the
      carbonyl stress) followed by further increase of AGEs and elevation of AOPP
      (marker of oxidative stress) in patients with progressive disease. As the
      clinical significance of these observations is currently uncertain further
      studies are clearly warranted, especially with respect to their potential
      therapeutic implications.

PMID- 17447854
TI  - Isotype class switching after transplantation in multiple myeloma.
AB  - Switching of the paraprotein isotype or transient presence of oligoclonal bands
      detectable by serum immunofixation electrophoresis has been reported following
      not only transplantations, but also after intensive chemotherapy for leukemia.
      Retrospective analysis of 72 transplanted myeloma patients was carried out to
      determine the frequency and clinical significance of the appearance of abnormal
      proteins bands (APB) distinct from the original paraprotein. APB presence was
      observed in 31 patients (43%) already after the first autotransplant, the median
      interval from transplant was 2 months (range, 1 to 6 months). The most frequent
      occurrence of APB was observed after allogeneic transplantation. In the group of
      patients with APB presence more patients achieved complete remission (32.2%
      versus 17.1%), statistically significant differences were also established when
      we compared the percentage of surviving patients and overall survival, to the
      present date, among both groups of patients (p=0.03). All relapsed patients with
      previous isotype class switching had disease characterized by the same type of
      paraprotein as that detected at diagnosis. The development of APB is likely
      related to the recovery of impaired immunoglobulin production after
      transplantation. We confirmed favourable prognostic significance of this finding
      in transplanted myeloma patients.

PMID- 17447855
TI  - Influence of heating on the activity of xanthine oxidase in tumor cells subjected
      to the phototoxic action of hematoporphyrin derivative.
AB  - The aim of this study was to clarify the mechanism of the stimulatory effect of
      heat stress on generation of superoxide radical (O2-*) in tumors subjected to
      photodynamic therapy (PDT) with hematoporphyrin derivative (HPD). For this
      purpose, the effect of heating on the activity of xanthine oxidase (XOD) in tumor
      cells upon their photosensitization with HPD was examined; this enzyme is
      participated in purine catabolism and has the ability to generate O2-*, a
      precursor of H2O2 and very cytotoxic hydroxyl radical. The study was carried out
      on Ehrlich ascites carcinoma (EAC) cells, which were loaded with HPD in a serum
      free medium and then irradiated with red light (lambda max = 630 nm) at 3
      different temperatures (30, 37 and 44 degrees C). In the cells, the activity of
      XOD was assayed fluorometrically, using pterine as the substrate, whereas the
      production of O2-* by the nitro blue tetrazolium method. It was found that
      increasing of the temperature from 30 to 44 degrees C strongly (by approximately
      2.5-fold) enhanced the generation of O2-* in EAC cells that correlated well with
      an increase in the rate of their photosensitized killing. Experiments showed that
      the intensification of O2-* formation could be mediated by the stimulatory
      effects of heating on the activity of XOD; namely, the 12 min treatment of EAC
      cells by HPD-PDT at a control (30 degrees C) temperature caused an about 2-fold
      growth in the activity of XOD, whereas the same light exposure at 44 degrees C
      led already to a 2.7-fold increase in the activity of this enzyme. However,
      incubation of EAC cells in the dark even at a hyperthermic (44 degrees C)
      temperature had no effect on their XOD activity. Thus, our findings strongly
      suggest that upon PDT with HPD the mild hyperthermia (approximately 44 degrees C)
      produced by photoirradiation might enhance the PDT-induced oxidative stress and,
      as a result, its tumoricidal effect via a rise in the activity of XOD. Besides,
      the obtained results suggest that severe hyperthermia (> 45 degrees C) could
      induce, contrary to mild hyperthermia, a reduction in the efficiency of HPD-PDT;
      we found that in EAC cells the raising temperature of an environment from 30 to
      44 degrees C induced more than 2-fold increase in the activity of XOD, whereas
      further heating from 44 to 60 degrees C led to inactivation of this enzyme.

PMID- 17447856
TI  - Association of cyclin D1 G870A polymorphism with susceptibility to gastric
      cancers in Korean male patients.
AB  - Cyclin D1 is a key cell cycle regulator that is upregulated in gastric cancer.
      The common G870A polymorphism of cyclin D1 which can influence cancer
      susceptibility and disease outcome has been the most frequently investigated. The
      specific aim of this study is to investigate whether the G870A polymorphism of
      cyclin D1 was associated with individual susceptibility to gastric cancer in
      Korea. The frequency of the polymorphism was examined in 253 gastric cancer
      patients and 442 healthy controls. Polymorphism analysis was performed by
      amplifying exon 4 of cyclin D1 and sequencing the products. The frequencies of
      genotypes: G/G, G/A and A/A were 28.1% (71/253), 49.4% (125/253) and 22.5%
      (57/253), respectively, in gastric cancer cases, and 23.1%, 51.1% and 25.8%,
      respectively, in healthy controls. Statistically, the polymorphism was not
      associated with increased risk of gastric cancer. When stratified by histological
      subtype of gastric cancer, the risk was also not statistically significant.
      However, the male gastric cancer patients showed a significantly higher
      proportion of the homozygous G/G genotype and the G allele (Chi-Square test, P =
      0.0242 & P = 0.0307) compared to males in the control group. Thus, our findings
      suggested that the G870A polymorphism of cyclin D1 was not associated with an
      increased risk for gastric cancer in this population, however, it may contribute
      to susceptibility to gastric cancer in men.

PMID- 17447858
TI  - Increasing the repetition frequency of electric pulse delivery reduces unpleasant
      sensations that occur in electrochemotherapy.
AB  - Involuntary muscle contractions and painful sensations during electric pulse
      delivery are the most unpleasant side effects of electrochemotherapy. The aim of
      this study was to determine the nature of pain caused by the application of
      electric pulses and to evaluate patients tolerance to the standard electric
      pulses of 1 Hz repetition frequency and the new 5 kHz protocol. A train of eight
      electric pulses of 1 Hz and 5 kHz repetition frequencies was delivered to the
      forearms of 40 healthy volunteers. After the conclusion of each protocol the
      subjects had to complete the short-form McGill Pain Questionnaire with separate
      visual analog scales for pain intensity and unpleasantness. All subjects selected
      at least one superficial and one deep pain descriptor; 85% selected at least two
      superficial descriptor and 60% at least two deep description. The application of
      5 kHz electric pulses was less unpleasant than the standard 1 Hz pulses; however,
      the pain intensity did not differ between the protocols. Significantly more
      subjects chose the new 5 kHz protocol as their choice of treatment (P = 0.017).
      The frequent use of deep descriptors in our study indicates that muscle
      contractions contribute to the discomfort felt by the subjects during the
      delivery of electric pulses. The new 5 kHz protocol considerably shortens the
      treatment session and is also better tolerated. Therefore, the new 5 kHz
      electrochemotherapy protocol should eventually replace the 1 Hz pulses as new
      standard.

PMID- 17447857
TI  - Paclitaxel, bleomycin, etoposide, and cisplatin (T-BEP) as initial treatment in
      patients with poor-prognosis germ cell tumors (GCT): a phase II study.
AB  - First line treatment of patients pts with poor-prognosis GCT, using BEP, is
      unsatisfactory. T-BEP (paclitaxel followed by BEP) demonstrated promising
      efficacy in the group of pts with intermediate and poor prognosis GCT. We present
      the results achieved with 1st line T-BEP in pts with poor-prognosis CGT. Twenty
      four pts received T-BEP as initial therapy. Three pts (12.5%) had primary
      mediastinal GCT. Four cycles of T-BEP were given 21 days apart. Paclitaxel 175
      mg/m2 was administered on day 1 before administration of BEP. The administration
      of G-CSF was not scheduled. Surgical resection of all radiographic residua was
      considered. All pts were assessable for response. Complete or partial response
      with negative tumor markers was achieved in 13 pts (54.2%; CI 95%: 34.3-74.1%).
      Median follow-up is 35.6 months. Median survival was not achieved and median time
      to-progression is 9.5 months. Myelosuppression was the major toxicity with Gr3-4
      granulocytopenia experienced in 52.1% of all courses. There were two treatment
      related deaths due to sepsis. Patients treated with 1st line T-BEP didn't achieve
      higher response rate or time to progression. However, the overall survival
      observed in our study is surprisingly long. We do not recommend using this
      regimen without G-CSF support due to substantial toxicity.

PMID- 17447859
TI  - Effect of prolonged psychoemotional stress and melatonin on experimental mammary
      carcinogenesis in female rats.
AB  - The aim of the present study was to determine whether prolonged stress repeated
      immobilization in boxes during the period of 18 weeks (IMS) influenced
      development and progression of N-methyl-N-nitrosourea (NMU)-induced mammary
      tumors in female Sprague-Dawley rats and whether long-term MEL application
      affected changes caused by stress. NMU was applied intraperitoneally in two doses
      each of 50 mg/kg b.w. between 40-50 postnatal days. Melatonin (MEL) was
      administered in drinking water in a concentration of 4 microg/ml (daily from 3
      p.m to 8 a.m), application was initiated 3 days prior to first NMU dose and
      lasted until the end of the experiment. Immobilization (2 h/day) began on the
      fifth day after second carcinogen application, animals were immobilized three
      times a week. Repeated immobilization of rats during 18 weeks decreased tumor
      frequency per group and per animal by 30% and tumor volume gain by 16% as opposed
      to control (NMU) animals. Combination of repeated immobilization and a long-term
      MEL application lowered incidence by 13% when compared to control, prolonged
      latency by 13%, decreased tumor frequency per group (by 44%) and per animal (by
      35%). Tumor volume gain increased by 35% but their cumulative volume prominently
      decreased by 74% as opposed to control. Tumor volume was the most markedly
      influenced by MEL, induced tumors developed more rapidly tumor volume gain
      increased by 61%. However, their cumulative volume markedly decreased by 75% when
      compared to immobilized group drinking water. Prolonged stress inhibited
      development and progression of NMU-induced mammary gland tumors in female rats
      and this effect was enhanced by long-term melatonin administration.

PMID- 17447860
TI  - Sentinel node biopsy in breast cancer: short time results show appropriate
      regional control.
AB  - Sentinel node biopsy becomes a standard diagnostic and therapeutic tool in breast
      cancer in certain indications, while in other indications its validity is still
      reviewed. The authors present their experience with this method. In the years
      2000-2006 700 patients underwent surgery. 704 sentinel node biopsies were
      performed (bilaterally in 4 cases), 7 times surgery was unsuccessful. In the
      unsuccessful cases immediate axillary lymph node dissection (ALND) was performed.
      985 sentinel nodes were found, the average was 1.4 nodes, maximum 6 nodes. In 7
      patients contralateral ALND for node positive contralateral cancer was necessary
      along with sentinel node biopsy. A positive sentinel lymph node (SLN) was found
      in 188 (26.9%) patients. A strong correlation between tumor size and lymph node
      positivity was found, 5.3% in pT1a, and 40.4% in pT2, respectively. The sentinel
      node metastases could be divided according to their size. The number of affected
      further nodes did correlate with this size, yet with the exception of isolated
      tumor cell detection, small size metastases did not exclude the possibility of
      further affection. Our findings support the role of sentinel node biopsy in
      breast cancer. 332 patients reached at least 2 years of follow up by the time of
      statistic evaluation, 2.5% of SLN negative and 5.6% of SLN positive patients
      experienced a recurrence. All of these recurrences were distant with no regional
      (axillary) involvement to this date. We conclude that sentinel node biopsy is not
      only a safe and accurate diagnostic tool, but it also provides acceptable
      regional control of the disease.

PMID- 17447861
TI  - Forensic injury biomechanics.
AB  - Forensic injury biomechanics is the science that relates mechanical forces to
      disruption of anatomical regions of the human body. In this review, we introduce
      (a) how scaling techniques can be used to describe injury severity and
      probability of death; (b) how a simple ratio, the factor of risk, and more
      sophisticated injury risk functions can be used to determine the probability of
      injury; and (c) how injury criteria (also known as tolerance limits) are defined
      for the head and neck. Methods for establishing injury causation are then
      illustrated by real-world examples drawn from litigation involving motor vehicle
      collisions and slips, trips and falls. Those factors that distinguish litigation
      from basic and applied research are also discussed, including the criteria for
      admissibility of expert opinions and the level of certainty used as the basis for
      these opinions. The criteria that must be met to support opinions on causation at
      both epidemiological and individual levels are also noted. If the expert
      appreciates the difference between the demands of ligation and those of basic and
      applied research, expert opinion can play a crucial role in the decision-making
      process that characterizes litigation. Because forensic injury biomechanics is
      central to opinions on injury causation, and because causation is often the key
      to determinations of who is at fault, forensic injury biomechanics can be the
      deciding factor in many personal injury, products and premises liability,
      wrongful death, and criminal cases.

PMID- 17447862
TI  - The RNA degradosome of Escherichia coli: an mRNA-degrading machine assembled on
      RNase E.
AB  - The RNA degradosome of Escherichia coli is a multiprotein complex involved in the
      degradation of mRNA. The principal components are RNase E, PNPase, RhlB, and
      enolase. RNase E is a large multidomain protein with an N-terminal catalytic
      region and a C-terminal noncatalytic region that is mostly natively unstructured
      protein. The noncatalytic region contains sites for binding RNA and for protein
      protein interactions with other components of the RNA degradosome. Several recent
      studies suggest that there are alternative forms of the RNA degradosome depending
      on growth conditions or other factors. These alternative forms appear to modulate
      RNase E activity in the degradation of mRNA. RNA degradosome-like complexes
      appear to be conserved throughout the Proteobacteria, but there is a surprising
      variability in composition that might contribute to the adaptation of these
      bacteria to the enormously wide variety of niches in which they live.

PMID- 17447863
TI  - Effects of tailored feedback on multiple health behaviors.
AB  - BACKGROUND: The effects of tailored intervention on multiple behaviors and
      possible moderators of tailoring effects have not yet been sufficiently
      demonstrated. PURPOSE: The purpose of this study was to examine the effectiveness
      of a computer-tailored intervention on smoking; physical activity; and fruit,
      vegetable, and fat intake; and to test potential moderators of the effectiveness
      (BMI, age, SES, gender, motivation, and the number of behaviors for which
      respondents met the recommendations from national guidelines). METHODS:
      Respondents were randomly assigned to a tailored intervention group, receiving
      one tailored letter on all of these behaviors, or a control intervention group,
      receiving one general information letter on all behaviors. RESULTS: Three months
      after the baseline assessment, the tailored intervention group showed
      significantly better effects than the control group for all behaviors studied,
      except for smoking. Notably, the intervention did not enhance the health
      behaviors, but rather reduced a decline in these behaviors during the 3-month
      study interval. Effect sizes were small. No moderating factors were found, except
      for the number of behaviors for which recommendations were met in the tailoring
      intervention group on fruit consumption. The largest effects of the tailored
      intervention were found for fruit in respondents who did not meet the
      recommendations for any behavior (Cohen's d = 0.3). CONCLUSIONS: A tailored
      intervention on multiple behaviors had significant, but limited effects when
      compared to generic information. The number of bad habits influenced the effects
      of the tailored intervention on fruit consumption.

PMID- 17447864
TI  - Choice of interactive dance and bicycle games in overweight and nonoverweight
      youth.
AB  - BACKGROUND: Interactive video games are a popular alternative to physical
      activity in youth. One advancement in computer games are interactive games that
      use physical activity as a game playing controller, combining exercise and
      entertainment, or exertainment. PURPOSE: This study tested the reinforcing value
      and activity levels of interactive dance and bicycle race games in 18 overweight
      and 17 nonoverweight 8- to 12-year-old youth. METHODS: Reinforcing value was
      studied using a behavioral choice paradigm that provided children the opportunity
      to respond on progressive ratio schedules of reinforcement for a choice of either
      playing the video dance or bicycle game using a handheld video game controller or
      one of three options: dancing or bicycling alone, dancing or bicycling while
      watching a video, or playing the interactive dance or bicycle game. Reinforcing
      value was defined in relationship to the amount of responding children engaged in
      for either choice. RESULTS: Results showed the interactive dance game was more
      reinforcing than dancing alone or dancing while watching the video (p = .003),
      but there was no difference across bicycling conditions. Nonoverweight youth were
      more active when given the opportunity to play the interactive dance game than
      overweight children (p = .05). CONCLUSIONS: These results suggest that children
      may be motivated to be active when given the opportunity to play an interactive
      dance game.

PMID- 17447865
TI  - Physical activity and mental health outcomes during menopause: a randomized
      controlled trial.
AB  - BACKGROUND: Many women experience detriments in mental health during the
      menopausal transition. Physical activity may attenuate these adverse outcomes but
      few studies investigating such effects exist. PURPOSE: This study examined the
      effects of a 4-month randomized controlled exercise trial on mental health
      outcomes in 164 previously low-active middle-aged women (M age = 49.9; SD = 3.6).
      METHODS AND RESULTS: Participants completed body composition and fitness
      assessment and a battery of psychological measures at the beginning and end of a
      4-month randomized controlled exercise trial with three arms: walking, yoga,
      control. The results indicated that walking and yoga were effective in enhancing
      positive affect and menopause-related QOL and reducing negative affect. Women who
      experienced decreases in menopausal symptoms across the trial also experienced
      improvements in all positive mental health and QOL outcomes and reductions in
      negative mental health outcomes. Whether menopausal symptoms increased or
      decreased across the trial appeared to be determined in part by whether there
      were increases or decreases in cardiorespiratory fitness. CONCLUSIONS: Physical
      activity appears to enhance mood and menopause-related QOL during menopause,
      however, other aspects of mental health may be affected only as a result of
      reduction in menopausal symptoms. Increasing cardiorespiratory fitness could be
      one way to reduce menopausal symptoms.

PMID- 17447866
TI  - Avoidable pitfalls in behavioral medicine outcome research.
AB  - To secure the role of behavioral medicine in health care, researchers continue to
      improve the quality of their outcome studies. Despite the availability of
      guidelines for designing high quality clinical trials, however, we have noted
      two, unfortunately common, flaws in behavioral medicine outcome research that
      undermine these efforts. The first issue is that researchers recruit medical
      patients whose scores on psychological target measures are not elevated at
      pretest. Data are presented from quantitative reviews of cardiovascular and
      cancer populations to illustrate the impact of this protocol decision. It is
      demonstrated how magnitude of change and corresponding statistical power are
      greatly reduced when patients with few problems are enrolled. The second issue
      pertains to the failure of researchers to measure psychological change when the
      actual model to be tested is a mediational model such that successful treatment
      of psychological distress is presumed to account for good long-term health
      outcomes. Such lack of attention to protocol design can result in
      misinterpretation of obtained effects and can lead to premature dismissal of
      psychological treatment opportunities for physical disease. We suggest how these
      flaws can be avoided in the protocol design stage.

PMID- 17447867
TI  - Neuregulin-1 genotype moderates the association between job strain and early
      atherosclerosis in young men.
AB  - BACKGROUND: Although it is known that a given level of strain does not induce a
      corresponding CHD risk in all individuals, factors that predict groups at risk
      have remained unclear. Neuregulin-1 (NRG-1) has various roles in the development
      and function of the heart and autonomic nervous system. PURPOSE: We examined
      whether polymorphic variation in NRG-1 moderates the association between job
      strain and early atherosclerosis. METHODS: The participants (M age = 32.5) were
      349 women and 357 men derived from the population-based Cardiovascular Risk in
      Young Finns study. Job strain was defined as the joint effect of job demands and
      job control. Preclinical atherosclerosis was measured using carotid intima-media
      thickness (IMT) ultrasound. RESULTS: NRG-1 single nucleotide polymorphism
      SNP8NRG221533 (T to C) was found to moderate the association between job strain
      and IMT in men (p = .04). Job strain was significantly associated with increased
      IMT among men with T/T genotype but not among the others. A direct association
      between NRG-1 and IMT was found in women. CONCLUSIONS: Our results suggest that
      the effect of job strain on early atherosclerosis is dependent on NRG-1 genotype
      in men. Gene x Environment Interaction approach seems to offer important
      additional information in stress research.

PMID- 17447868
TI  - Adoption and maintenance of four health behaviors: theory-guided longitudinal
      studies on dental flossing, seat belt use, dietary behavior, and physical
      activity.
AB  - BACKGROUND: Adoption and maintenance of health behaviors are often poorly
      predicted by behavioral intentions. To bridge the gap between intentions and
      behavior, strategic planning and recovery self-efficacy have been suggested as
      proximal predictors. PURPOSE: The aim was to examine the usefulness of a
      prediction model that includes planning and self-efficacy as postintentional
      mediator variables. METHODS: Four longitudinal studies were conducted on dental
      flossing (Study I, N = 157), seat belt use (Study II, N = 298), dietary behaviors
      (Study III, N = 700), and physical activity (Study IV, N = 365). Dental flossing
      and seat belt use were assessed in students by paper-and-pencil questionnaires,
      whereas dietary behavior and physical activity inventories were presented to the
      general public in the internet. RESULTS: By structural equation modeling, it was
      found that one common model fits all four data sets well. Results differed in
      terms of variance accounted for, but the overall patterns of estimated parameters
      were similar across samples. CONCLUSIONS: Self-efficacy and planning seemed to be
      functional as proximal predictors of health behaviors, whereas health risk
      perception appeared to be a negligible factor. When predicting health behaviors,
      self-regulatory variables should be used in addition to the behavioral intention.

PMID- 17447869
TI  - Response expectancies, treatment credibility, and hypnotic suggestibility:
      mediator and moderator effects in hypnotic and cognitive-behavioral pain
      interventions.
AB  - BACKGROUND: Several studies have shown that response expectancies are an
      important mechanism of popular psychological interventions for pain. However,
      there has been no research on whether response expectancies and treatment
      credibility independently mediate hypnotic and cognitive-behavioral pain
      interventions and whether the pattern of mediation is affected by experience with
      the interventions. Also, past research has indicated that hypnotic pain
      interventions may be moderated by hypnotic suggestibility. However, these studies
      have typically failed to measure the full range of suggestibility and have
      assessed pain reduction and suggestibility in the same experimental context,
      possibly inflating the association between these variables. PURPOSE: To clarify
      the mediator role of response expectancies and treatment credibility, and the
      moderator role of hypnotic suggestibility in the hypnotic and cognitive
      behavioral reduction of pain. METHODS: Approximately 300 participants were
      assessed for suggestibility. Then, as part of an apparently unrelated experiment,
      124 of these individuals received analogue cognitive-behavioral, hypnotic, or
      placebo control pain interventions. RESULTS: Response expectancies and
      credibility independently mediated treatment. The extent of mediation increased
      as participants gained more experience with the interventions. Suggestibility
      moderated treatment and was associated with relief only from the hypnotic
      intervention. CONCLUSIONS: Response expectancies and treatment credibility are
      unique mechanisms of hypnotic and cognitive-behavioral pain interventions.
      Hypnotic suggestibility predicts relief from hypnotic pain interventions and this
      association is not simply an artifact of measuring suggestibility and pain
      reduction in the same experimental context. The relationship between
      suggestibility and hypnotic pain reduction appears to be linear in nature.

PMID- 17447870
TI  - Adjustment to chronic pain: the role of pain acceptance, coping strategies, and
      pain-related cognitions.
AB  - BACKGROUND: Previous research has found that acceptance of pain is more
      successful than coping variables in predicting adjustment to pain. PURPOSE: To
      compare the influence of acceptance, pain-related cognitions and coping in
      adjustment to chronic pain. METHODS: One hundred seventeen chronic pain patients
      attending the Clinical Pain Unit were administered a battery of questionnaires
      assessing pain acceptance, active and passive coping, pain-related cognitions,
      and adjustment. RESULTS: The influence of acceptance, coping, and cognition on
      all the adjustment variables was considered simultaneously via Structural
      Equation Modeling using LISREL 8.30 software. A multigroup analysis showed that
      the male and female samples did not significantly differ regarding path
      coefficients. The final model showed that acceptance of pain determined
      functional status and functional impairment. However, coping measures had a
      significant influence on measures of emotional distress. Catastrophizing self
      statements significantly influenced reported pain intensity and anxiety;
      resourcefulness beliefs had a negative and significant influence on depression.
      CONCLUSIONS: These findings suggest that acceptance may play a critical role in
      the maintenance of functioning and, with this aim, acceptance-based treatments
      are promising to avoid the development of disability. They also lend support to
      the role of control beliefs and of active coping to maintain a positive mood.
      Acceptance and coping are presented as complementary approaches.

PMID- 17447871
TI  - Changes in smoking associated with an acute health event: theoretical and
      practical implications.
AB  - BACKGROUND: Experiencing a serious adverse behavior-related consequence may
      motivate behavior change. PURPOSE: To examine how a sentinel health event is
      associated with changes in smoking. METHODS: We used a prospective cohort design.
      Adult emergency department (ED) patients provided demographic data, a smoking
      history, ratings of quit intentions, and endorsement of self-identified smoking
      related health problems. A chart review collected data on acuity, ED disposition,
      and medical diagnoses. Smoking was reassessed 1 month postvisit. Hierarchical
      regression analyses were conducted to predict (a) intention to quit, (b) any quit
      attempt of 24 hr or more, and (3) 7-day abstinence. RESULTS: Of 717 smokers
      enrolled, 189 (26%) intended to quit within the next month. Of the 253
      participants reached 1 month postvisit, 126 (50%) reported they had attempted to
      quit, with 44 (19%) reporting 7-day abstinence. After controlling for other
      predictors, several event-related variables, such as having a smoking-related ED
      visit and being admitted to the hospital, were strong predictors of outcomes.
      CONCLUSION: Compared to community-based estimates, many more smokers in our
      sample attempted to quit and achieved 7-day abstinence. This was especially true
      among smokers who attributed their ED visit to a smoking-related health problem
      and who were admitted to the hospital. We discuss the implications for tobacco
      intervention design in medical settings.

PMID- 17447872
TI  - Older adults' preferences for exercising alone versus in groups: considering
      contextual congruence.
AB  - BACKGROUND: A growing body of research suggests that older exercisers prefer to
      exercise alone rather than in group-based settings. One limitation of these
      studies, however, has been that researchers have failed to take into account the
      age-related characteristics of groups when asking adults about their preferences
      for exercise settings. PURPOSE: The overall purpose of this study was to examine
      the exercise preferences of 947 adults for involvement in standard exercise
      classes populated by participants from various categories across the age
      spectrum. RESULTS: The results revealed that when faced with the prospect of
      exercising with considerably older or younger exercisers, participants found such
      an exercise context to be largely unappealing. However, in accordance with the
      basic tenets of self-categorization theory, the results revealed that older and
      younger adults alike express a positive preference for exercising in standard
      exercise classes comprised of similarly aged participants. CONCLUSIONS: The
      findings of this study challenge a growing call for exercise interventions for
      older adults to be primarily directed at the individual-level, and suggest that
      group-related intervention strategies may indeed be attractive to older
      exercisers.

PMID- 17447873
TI  - Feasibility and utility of an electronic diary to assess self-report symptoms in
      patients with inflammatory bowel disease.
AB  - BACKGROUND: Self-report items from the Crohn's Disease Activity Index (CDAI) are
      completed using a 7-day paper diary; however, there are reports of protocol
      deviations by both patients and researchers/clinicians. The self-report
      literature has demonstrated these deviations can distort the information
      collected by introducing recall bias, especially for subjective measures like
      pain and well-being. PURPOSE: The purpose of this pilot study is to evaluate the
      feasibility of using an electronic diary to collect symptom self-reports.
      METHODS: Sixteen patients with Inflammatory Bowel Disease completed entries on
      the diary 12 times per day for 3 weeks. The diary included "user-friendly"
      features that made it easier to incorporate into their daily lives. RESULTS:
      Despite 2 compliance outliers, the overall compliance was 88%; when these
      outliers were removed compliance increased to 92%. Participants used the diary
      features appropriately and completed a substantial number of assessments per day.
      Although overall compliance declined significantly over the 3-week study period,
      the number of prompts completed did not change significantly over time.
      CONCLUSIONS: Limitations include the small sample size, but despite this
      limitation this report supports the feasibility of collecting symptom information
      using an electronic diary. Future studies are needed to evaluate the possibility
      of using an electronic diary to collect the CDAI self-report information in both
      clinical and research settings.

PMID- 17447874
TI  - Two-year follow-up of sequential and simultaneous interactive computer-tailored
      interventions for increasing physical activity and decreasing fat intake.
AB  - BACKGROUND: Limited evidence exists on long-term efficacy of interactive computer
      tailored interventions for increasing physical activity and decreasing fat
      intake, and even more so when they are implemented simultaneously or
      sequentially. PURPOSE: This study aims to examine long-term efficacy of
      interactive computer-tailored physical activity and fat intake interventions, and
      evaluate their efficacy in a simultaneous or sequential implementation over 2
      years. METHODS: Participants (392) were randomly assigned to a simultaneous group
      receiving both interventions at baseline; a sequential group first receiving the
      physical activity intervention and 3 months later the fat intake intervention;
      and a sequential group first receiving the fat intake intervention and 3 months
      later the physical activity intervention. RESULTS: Strong time effects were seen
      for total physical activity (F = 38.7, p < .001) and fat intake (F = 103.9, p <
      .001), indicating that intervention effects remained over 2 years for those
      participants that were still available for the 2-year follow-up. At 2-year follow
      up the interventions resulted in a 10% and a 27% increase of participants that
      met public health recommendations for physical activity and fat intake,
      respectively. Overall the interventions were more effective for participants not
      meeting the public health recommendations at baseline. The sequential
      intervention mode was overall slightly more effective than the simultaneous mode
      in maintaining intervention effects. CONCLUSIONS: Both interventions showed
      efficacy in maintaining long-term health behavior changes. More research is
      needed on sequential and simultaneous intervening modes.

PMID- 17447877
TI  - Endostatin: current concepts about its biological role and mechanisms of action.
AB  - Endogenous inhibitors of angiogenesis are proved to be a major factor preventing
      the emergence of clinically manifested stages of human cancer. The protein
      endostatin, a 20-kD proteolytic fragment of type XVIII collagen, is one of the
      most active natural inhibitors of angiogenesis. Endostatin specifically inhibits
      the in vitro and in vivo proliferation of endothelial cells, inducing their
      apoptosis through inhibition of cyclin D1. On the surface of endothelial cells,
      endostatin binds with the integrin alpha(5)beta(1) that activates the Src-kinase
      pathway. The binding of endostatin with integrins also down-regulates the
      activity of RhoA GTPase and inhibits signaling pathways mediated by small kinases
      of the Ras and Raf families. All these events promote disassembly of the actin
      cytoskeleton, disorders in cell-matrix interactions, and decrease in
      endotheliocyte mobility, i.e., promote the suppression of angiogenesis.
      Endostatin displays a high antitumor activity in vivo: it inhibits the
      progression of more than 60 types of tumors. This review summarizes results of
      numerous studies concerning the biological activity and action mechanism of
      endostatin.

PMID- 17447878
TI  - Interaction of aminoacyl-tRNA synthetases with tRNA: general principles and
      distinguishing characteristics of the high-molecular-weight substrate
      recognition.
AB  - This review summarizes results of numerous (mainly functional) studies that have
      been accumulated over recent years on the problem of tRNA recognition by
      aminoacyl-tRNA synthetases. Development and employment of approaches that use
      synthetic mutant and chimeric tRNAs have demonstrated general principles
      underlying highly specific interaction in different systems. The specificity of
      interaction is determined by a certain number of nucleotides and structural
      elements of tRNA (constituting the set of recognition elements or specificity
      determinants), which are characteristic of each pair. Crystallographic structures
      available for many systems provide the details of the molecular basis of
      selective interaction. Diversity and identity of biochemical functions of the
      recognition elements make substantial contribution to the specificity of such
      interactions.

PMID- 17447879
TI  - Topography of the active site of the Saccharomyces cerevisiae plasmalemmal
      dicarboxylate transporter studied using lipophilic derivatives of its substrates.
AB  - 2-Alkylmalonates and O-acyl-L-malates have been found to competitively inhibit
      the dicarboxylate transporter of Saccharomyces cerevisiae cells, and the
      substrate derivatives chosen did not penetrate across the plasmalemma under the
      experiment conditions. Probing of the active site of this transporter has
      revealed a large lipophilic area stretching between the 0.72 to 2.5 nm from the
      substrate-binding site. Itaconate inhibited the transport fivefold more
      effectively than L-malate. This suggests the existence of a hydrophobic region
      immediately near the dicarboxylate-binding site (to 0.72 nm). The yeast
      plasmalemmal transporter was different from the rat liver mitochondrial
      dicarboxylate transporter. An area with variable lipophilicity adjoining the
      substrate-binding site has been revealed in the latter by a similar method. This
      area is mainly hydrophobic at distances up to 1.76 nm from the binding site and
      is separated by a hydrophilic region from 0.38 to 0.88 nm. Fumarate but not
      maleate competitively inhibited succinate transport into the S. cerevisiae cells.
      It is suggested that the plasmalemmal transporter binds the substrate in the
      trans-conformation. The prospects of the proposed approach for scanning
      lipophilic profiles of channels of different transporters are discussed.

PMID- 17447880
TI  - Effects of oxygen and photosynthesis carbon cycle reactions on kinetics of P700
      redox transients in cyanobacterium Arthrospira platensis cells.
AB  - Effects of oxygen and photosynthesis and respiration inhibitors on the electron
      transport in photosystem I (PSI) of the cyanobacterium Arthrospira platensis
      cells were studied. Redox transients of P700 were induced by illumination at 730
      nm and monitored as kinetics of the absorption changes at 810 nm; to block
      electron influx from PSII, the measurements were performed in the presence of 30
      microM 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). Inhibitors of terminal
      oxidases (potassium cyanide and pentachlorophenol) insignificantly influenced the
      fast oxidation of P700 under aerobic conditions, whereas removal of oxygen
      significantly decelerated the accumulation of P700(+). In the absence of oxygen
      the slow oxidation of P700 observed on the first illumination was accelerated on
      each subsequent illumination, suggesting an activation of the carbon cycle
      enzymes. Under the same conditions, pentachlorophenol (an uncoupler) markedly
      accelerated the P700 photooxidation. Under anaerobic conditions, potassium
      cyanide (an inhibitor of carbon dioxide assimilation) failed to influence the
      kinetics of redox transients of P700, whereas iodoacetamide (an inhibitor of
      NADP(H)-glyceraldehyde-3-phosphate dehydrogenase) completely prevented the
      photooxidation of P700. Thus, the fast photooxidation of P700 in the A. platensis
      cells under aerobic conditions in the presence of DCMU was caused by electron
      transport from PSI onto oxygen, and complicated transient changes in the P700
      photooxidation kinetics under anaerobic conditions (in the presence of DCMU) were
      due to involvement of NADP+ generated during the reducing phase of the carbon
      cycle.

PMID- 17447881
TI  - New mutations in the human p53 gene--a regulator of the cell cycle and
      carcinogenesis.
AB  - Mutations in the tumor suppressor gene p53 often lead to disarrangement of the
      cell cycle and of genetic integrity control of cells that may contribute to tumor
      development. We studied p53 gene mutations in 26 primary tumors of colorectal
      cancer patients. Mutations in p53 were found in 17 tumors (65.4%). All point
      mutations affected the DNA binding domain of p53 and were localized in exons 4-8
      of the gene. Mutant p53 isoforms with altered domain structure and/or with
      alternative C-terminus arising from frameshift mutations or abnormal splicing
      were found in six tumors. Mutations Leu111Gln and Ser127Phe were shown in
      colorectal cancer for the first time. Isoforms p53-305 with C(4) insertion in
      codons 300/301 and p53i9* including an additional 44 nucleotides of the 3 -end of
      intron 9 were discovered for the first time. Mutations of p53 were associated
      with lymph node metastases and III/IV stage of tumors that are signs of
      unfavorable prognosis in colorectal cancer.

PMID- 17447882
TI  - A novel method for packing quality assessment of transmembrane alpha-helical
      domains in proteins.
AB  - Here we present a novel method for assessment of packing quality for
      transmembrane (TM) domains of alpha-helical membrane proteins (MPs), based on
      analysis of available high-resolution experimental structures of MPs. The
      presented concept of protein-membrane environment classes permits quantitative
      description of packing characteristics in terms of membrane accessibility and
      polarity of the nearest protein groups. We demonstrate that the method allows
      identification of native-like conformations among the large set of theoretical MP
      models. The developed "membrane scoring function" will be of use for optimization
      of TM domain packing in theoretical models of MPs, first of all G-protein coupled
      receptors.

PMID- 17447883
TI  - Proteinase inhibitors from the tropical sea anemone Radianthus macrodactylus:
      isolation and characteristic.
AB  - Two new serine proteinase inhibitors (RmIn I and RmIn II) from the tropical sea
      anemone Radianthus macrodactylus have been isolated and characterized. The
      purification procedure includes polychrome-1 hydrophobic chromatography, Superdex
      Peptide 10/30 FPLC, and Nucleosil C(18) reverse-phase HPLC. The molecular masses
      of RmIn I, RmIn II, and the complexes RmIn II/trypsin and RmIn I,II/alpha
      chymotrypsin have been determined. The K(i) values of RmIn I and RmIn II for
      trypsin and alpha-chymotrypsin have been determined. The polypeptides RmIn I and
      RmIn II are shown to be nontoxic and to exhibit antihistamine activity. The N
      terminal amino acid sequences of RmIn I (GICSEPIVVGPCKAG-) and RmIn II
      (GSTCLEPKVVGPCKA-) have been determined. A high homology of the amino acid
      sequences is demonstrated for the proteinase inhibitors produced by such
      evolutionarily distant species as coelenterates, reptiles, and mammals.

PMID- 17447884
TI  - Additional stabilization of stem bromelain coupled to a thermosensitive polymer
      by uniform orientation and using polyclonal antibodies.
AB  - Stem bromelain was covalently coupled to a thermosensitive polymer of N
      isopropylacrylamide (p(NIPAm)) either through the amino groups of the enzyme
      (randomly coupled) or via the lone oligosaccharide chain (uniformly coupled). The
      enzyme coupled via the oligosaccharide chain exhibited better access to the
      substrate casein as compared to the preparation in which the amino groups formed
      the point of contact between the enzyme and the polymer. Native bromelain
      exhibited a pH optimum of 8.0 and a broad pH-activity profile. The polymer
      coupled preparations exhibited broader pH-activity profiles and shifting of pH
      optimum to 10.0 at 35 degrees C. At 25 degrees C, the shifting of pH optimum was
      observed for the randomly coupled enzyme only. The temperature-activity profiles
      of bromelain coupled to p(NIPAm) also showed appreciable broadening and the
      preparations retained greater fraction of maximum activity above the temperature
      optimum. The optimum temperature of the uniformly oriented preparation also rose
      to 70 degrees C. Inactivation rates of the polymer-coupled bromelain were
      remarkably low at 60 degrees C as compared to the native protease, and binding of
      antibromelain antibodies improved the resistance to inactivation of the polymer
      coupled preparations. The cleavage patterns of hemoglobin and IgG by the native
      bromelain and the polymer-coupled preparations were comparable.

PMID- 17447885
TI  - N-terminus deletion affecting the preparation of soluble cyanobacterial
      glutaredoxin in Escherichia coli.
AB  - Glutaredoxin has been implicated in maintenance of a normal cellular
      thiol/disufide ratio and the regeneration of oxidatively damaged proteins. In
      order to obtain more information about these important regulatory proteins in
      cyanobacteria, we have previously cloned and expressed the first cyanobacterial
      glutaredoxin gene ssr2061 in Escherichia coli. In this work, the second
      glutaredoxin gene slr1562 was studied. About 90% of Grx2061 coded by ssr2061 was
      produced in a soluble form while 90% of Grx1562 coded by slr1562 was found in
      inclusion bodies. To improve the production of soluble Grx1562, we constructed
      two mutants: Grx1562NC with cysteines in conserved site substituted by serines,
      and Grx1562M with N-terminus hydrophobic region deletion. Only the latter mutant
      was successfully expressed in soluble form with increased glutaredoxin activity
      and showed less sensitivity in oxidative stress. Spectroscopic analysis shows
      that the structure of Grx1562M with less hydrophobic nature could give more
      opportunity for protein solubility and could improve the substrate catalytic
      efficiency. These results suggest that hydrophobic N-terminus determines the
      insolubility of Grx1562 and may provide another strategy for increasing
      expression level of soluble heterologous proteins in E. coli.

PMID- 17447886
TI  - Mechanism of estrogen-induced apoptosis in breast cancer cells: role of the NF
      kappaB signaling pathway.
AB  - The ability of sex steroid hormones to up-regulate the apoptotic signaling
      proteins is well documented; however, the apoptotic potential of sex hormones is
      not remarkable and fully compensated by their growth stimulatory action to target
      cells. In the present study using the long-term cultivation of estrogen-dependent
      MCF-7 breast cancer cells in steroid-free medium, we have established a cell
      subline, designed as MCF-7/LS, which was characterized by the resistance to
      growth stimulatory estradiol action and hypersensitivity to estrogen-induced
      apoptosis. We have demonstrated that estrogen treatment of the cells does not
      influence on the level of TNF-R1 or Fas, but dramatically decreases the
      transcriptional activity of NF-kappaB. Importantly, the MCF-7/LS cells, which are
      insensitive to growth stimulatory estrogen action, retain the ability to decrease
      in the NF-kappaB activity in response to estrogen stimulus. Furthermore, the
      significant increase in the basal (in the absence of ligand) estrogen receptor
      (ER)-dependent transcriptional activity in the MCF-7/LS cells was revealed and
      reciprocal transcriptional antagonism between ER and NF-kappaB was demonstrated.
      Finally, we proved the possible involvement of phosphatidylinositol-3 kinase
      (PI3K) in the ligand-independent ER activation. In general, the results presented
      suggest that long-term growth of MCF-7 breast cancer cells in steroid-free medium
      is accompanied with the increase in the basal ER-dependent transcriptional
      activity as well as the maintenance of the negative regulatory loop ER-NF-kappaB.
      The latter may be considered as one of the factors resulting in a disbalance
      between pro- and anti-apoptotic pathways and enhancement in estrogen apoptotic
      action in the cells.

PMID- 17447887
TI  - "False" thymine-1H-Enol guanine base pair. low misinsertion rate by DNA
      polymerase explained by computational chemistry consideration.
AB  - Formation of correct TA and GC and "false" thymine-1H-enol guanine (TGenol) base
      pairs is here considered to control nucleotide insertion into DNA via low
      substrate concentration Michaelis-Menten controlled kinetics. Contributions of
      base pairing to formation of Gibbs free energies in water solution, DeltaDeltaG,
      are calculated for the correct and false base pairs with the semi-empiric
      MNDO/PM3 method for base pairing energies in vacuum and the BEM method for
      hydration effects. The results for DeltaDeltaG indicate equal insertion rates for
      correct base pairing and a 10(-3)-10(-4) error probability for false insertion
      controlled by the TGenol false pair.

PMID- 17447888
TI  - Chronic administration of coenzyme Q10 limits postinfarct myocardial remodeling
      in rats.
AB  - The effect of chronic coronary artery occlusion on the content of rat myocardial
      coenzymes Q (CoQ) and evaluation of the applicability of CoQ(10) for limiting
      postinfarct remodeling have been investigated. Left ventricle myocardium
      hypertrophy was characterized by the decrease in CoQ(9) (-45%, p < 0.0001),
      CoQ(10) (-43%, p < 0.001), and alpha-tocopherol (-35%, p < 0.05). There were no
      differences between the parameters of postinfarction and sham-operated rats in
      plasma. Administration of CoQ(10) (10 mg/kg) via a gastric probe for 3 weeks
      before and 3 weeks after occlusion maintained higher levels of CoQ in the
      postinfarction myocardium: the decrease in CoQ(9) and CoQ(10) was 25% (p < 0.05)
      and 23% (p < 0.05), respectively (versus sham-operated animals). Plasma
      concentrations of CoQ(10) were more than 2 times higher (p < 0.05). In CoQ
      treated rats there was significant correlation between plasma levels of CoQ and
      the infarct size: r = -0.723 (p < 0.05) and r = -0.839 (p < 0.01) for CoQ(9) and
      CoQ(10). These animals were also characterized by earlier and more intensive scar
      tissue formation in the postinfarction myocardium and also by more pronounced
      cell regeneration processes. This resulted in the decrease in both the infarct
      size (16.2 +/- 8.1 vs. 27.8 +/- 12.1%) and also mass index of left ventricle
      (2.18 +/- 0.24 vs. 2.38 +/- 0.27 g/kg) versus untreated rats (p < 0.05). Thus,
      long-term treatment with ubiquinone increases plasma and myocardial CoQ content
      and this can improve the survival of myocardial cells during ischemia and limit
      postinfarct myocardial remodeling.

PMID- 17447889
TI  - A new method for differential determination of basic natural forms of indolyl-3
      acetic acid.
AB  - A new ELISA method is proposed for differential quantitative determination of
      free (indolyl-3-acetic acid; IAA) and bound (indolyl-3-acetyl-L-aspartate) forms
      of natural auxins. There is similarity in results obtained by this and some
      traditionally used methods. The standard error of determination of the active
      form of IAA by our method is 1.5-2.0 times less than that using the traditional
      method. The method of quantitative differential determination of the main natural
      auxins does not require preliminary sample preparation, and this shortens assay
      time. The developed method has been used for practical determination of different
      forms of endogenous IAA in wheat and dandelion ovaries subjected to minimal
      treatment. This method can be used to investigate changes in the ratio of various
      hormonal forms of auxins that differ in their physiological activity in
      reproductive organs of angiosperms at various stages of reproduction.

PMID- 17447890
TI  - Extracellular alkaline proteinase of Colletotrichum gloeosporioides.
AB  - The main proteinase of the filamentous fungus Colletotrichum gloeosporioides
      causing anthracnoses and serious problems for production and storage of
      agricultural products has molecular mass of 57 kD and was purified more than 200
      fold to homogeneity with the yield of 5%. Maximal activity of the proteinase is
      at pH 9.0-10.0, and the enzyme is stable at pH 6.0-11.5 (residual activity not
      less than 70%). The studied enzyme completely kept its activity to 55 degrees C,
      with a temperature optimum of 45 degrees C. The purified C. gloeosporioides
      proteinase is stable at alkaline pH values, but rapidly loses its activity at pH
      values lower than 5.0. Addition of bovine serum albumin stabilizes the enzyme
      under acidic conditions. Data on inhibitor analysis and substrate specificity of
      the enzyme allow its classification as a serine proteinase of subtilisin family.
      It is demonstrated that the extracellular proteinase of C. gloeosporioides
      specifically effects plant cell wall proteins. It is proposed that the studied
      proteinase--via hydrolysis of cell wall--provides for penetration of the fungus
      into the tissues of the host plant.

PMID- 17447891
TI  - LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's
      disease mutants affect kinase activity.
AB  - Mutations in the LRRK2 (leucine-rich repeat kinase-2) gene cause late-onset PD
      (Parkinson's disease). LRRK2 contains leucine-rich repeats, a GTPase domain, a
      COR [C-terminal of Roc (Ras of complex)] domain, a kinase and a WD40 (Trp-Asp 40)
      motif. Little is known about how LRRK2 is regulated, what its physiological
      substrates are or how mutations affect LRRK2 function. Thus far LRRK2 activity
      has only been assessed by autophosphorylation and phosphorylation of MBP (myelin
      basic protein), which is catalysed rather slowly. We undertook a KESTREL (kinase
      substrate tracking and elucidation) screen in rat brain extracts to identify
      proteins that were phosphorylated by an activated PD mutant of LRRK2 (G2019S).
      This led to the discovery that moesin, a protein which anchors the actin
      cytoskeleton to the plasma membrane, is efficiently phosphorylated by LRRK2, at
      Thr558, a previously identified in-vivo-phosphorylation site that regulates the
      ability of moesin to bind actin. LRRK2 also phosphorylated ezrin and radixin,
      which are related to moesin, at the residue equivalent to Thr558, as well as a
      peptide (LRRKtide: RLGRDKYKTLRQIRQ) encompassing Thr558. We exploited these
      findings to determine how nine previously reported PD mutations of LRRK2 affected
      kinase activity. Only one of the mutations analysed, namely G2019S, stimulated
      kinase activity. Four mutations inhibited LRRK2 kinase activity (R1941H, I2012T,
      I2020T and G2385R), whereas the remainder (R1441C, R1441G, Y1699C and T2356I) did
      not influence activity. Therefore the manner in which LRRK2 mutations induce PD
      is more complex than previously imagined and is not only caused by an increase in
      LRRK2 kinase activity. Finally, we show that the minimum catalytically active
      fragment of LRRK2 requires an intact GTPase, COR and kinase domain, as well as a
      WD40 motif and a C-terminal tail. The results of the present study suggest that
      moesin, ezrin and radixin may be LRRK2 substrates, findings that have been
      exploited to develop the first robust quantitative assay to measure LRRK2 kinase
      activity.

PMID- 17447892
TI  - Rhizavidin from Rhizobium etli: the first natural dimer in the avidin protein
      family.
AB  - Rhizobium etli CFN42 is a symbiotic nitrogen-fixing bacterium of the common bean
      Phaseolus vulgaris. The symbiotic plasmid p42d of R. etli comprises a gene
      encoding a putative (strept)avidin-like protein, named rhizavidin. The amino acid
      sequence identity of rhizavidin in relation to other known avidin-like proteins
      is 20-30%. The amino acid residues involved in the (strept)avidin-biotin
      interaction are well conserved in rhizavidin. The structural and functional
      properties of rhizavidin were carefully studied, and we found that rhizavidin
      shares characteristics with bradavidin, streptavidin and avidin. However, we
      found that it is the first naturally occurring dimeric protein in the avidin
      protein family, in contrast with tetrameric (strept)avidin and bradavidin.
      Moreover, it possesses a proline residue after a flexible loop (GGSG) in a
      position close to Trp-110 in avidin, which is an important biotin-binding
      residue. [3H]Biotin dissociation and ITC (isothermal titration calorimetry)
      experiments showed dimeric rhizavidin to be a high-affinity biotin-binding
      protein. Its thermal stability was lower than that of avidin; although similar to
      streptavidin, it was insensitive to proteinase K. The immunological cross
      reactivity of rhizavidin was tested with human serum samples obtained from cancer
      patients exposed to (strept)avidin. No significant cross-reactivity was observed.
      The biodistribution of the protein was studied by SPECT (single-photon emission
      computed tomography) imaging in rats. Similarly to avidin, rhizavidin was
      observed to accumulate rapidly, mainly in the liver. Evidently, rhizavidin could
      be used as a complement to (strept)avidin in (strept)avidin-biotin technology.

PMID- 17447893
TI  - STAT5 isoforms: controversies and clarifications.
AB  - STAT (signal transducer and activator of transcription) family transcription
      factors are critical regulators of the development and differentiation of many
      cell types. STAT isoforms are generated by alternative splicing, but have also
      been suggested to be generated post-transcriptionally. In this issue of the
      Biochemical Journal, Schuster and colleagues have identified cathepsin G as the
      protease that cleaves full-length STAT5 (STAT5alpha) to generate a C-terminally
      truncated form in immature myeloid cells. However, the authors argue that this
      proteolytically generated isoform does not occur naturally in vivo; rather, it is
      artificially generated by cathepsin G during the preparation of cell extracts.
      This new evidence calls into question the physiological significance of this
      putative isoform and forces the general re-examination of proteolytically
      generated STAT isoforms.

PMID- 17447895
TI  - Crucial roles of binding sites for NF-kappaB and C/EBPs in IkappaB-zeta-mediated
      transcriptional activation.
AB  - IkappaB-zeta [inhibitor of NF-kappaB (nuclear factor kappaB) zeta] is a nuclear
      protein that is induced upon stimulation of TLRs (Toll-like receptors) and IL
      (interleukin)-1 receptor. IkappaB-zeta harbours C-terminal ankyrin repeats that
      interact with NF-kappaB. Our recent studies have shown that, upon stimulation,
      IkappaB-zeta is essential for the induction of a subset of inflammatory genes,
      represented by IL-6, whereas it inhibits the expression of TNF (tumour necrosis
      factor)-alpha. In the present study, we investigated mechanisms that determine
      the different functions of IkappaB-zeta. We found that co-expression of IkappaB
      zeta and the NF-kappaB subunits synergistically activates transcription of the
      hBD-2 (human beta-defensin 2) and NGAL (neutrophil gelatinase-associated
      lipocalin) genes, whereas it inhibits transcription of E-selectin. Reporter
      analyses indicated that, in addition to an NF-kappaB-binding site, a flanking
      C/EBP (CCAAT/enhancer-binding protein)-binding site in the promoters is essential
      for the IkappaB-zeta-mediated transcriptional activation. Using an artificial
      promoter consisting of the NF-kappaB- and C/EBP-binding sites, transcriptional
      activation was observed upon co-transfection with IkappaB-zeta and NF-kappaB,
      indicating that these sequences are minimal elements that confer the IkappaB-zeta
      mediated transcriptional activation. Chromatin immunoprecipitation assays and
      knockdown experiments showed that both IkappaB-zeta and the NF-kappaB subunits
      were recruited to the NGAL promoter and were essential for the transcriptional
      activation of the hBD-2 and NGAL promoters on stimulation with IL-1beta. The
      activation of the NGAL promoter by transfection of IkappaB-zeta and NF-kappaB was
      suppressed in C/EBPbeta-depleted cells. Thus IkappaB-zeta acts as an essential
      transcriptional activator by forming a complex with NF-kappaB on promoters
      harbouring the NF-kappaB- and C/EBP-binding sites, upon stimulation of TLRs or IL
      1 receptor.

PMID- 17447896
TI  - Molecular characterization of centerin, a germinal centre cell serpin.
AB  - Centerin [SERPINA9/GCET1 (germinal centre B-cell-expressed transcript 1)] is a
      serpin (serine protease inhibitor) whose expression is restricted to germinal
      centre B-cells and lymphoid malignancies with germinal centre B-cell maturation.
      Expression of centerin, together with bcl-6 and GCET2, constitutes a germinal
      centre B-cell signature, which is associated with a good prognosis in diffuse
      large B-cell lymphomas, but the molecular basis for this remains to be
      elucidated. We report here the cloning, expression and molecular characterization
      of bacterial recombinant centerin. Biophysical studies demonstrated that centerin
      was able to undergo the 'stressed to relaxed' conformational change which is an
      absolute requirement for protease inhibitory activity. Kinetic analysis showed
      that centerin rapidly inhibited the serine protease trypsin (k(a)=1.9x10(5) M(-1)
      x s(-1)) and also demonstrated measurable inhibition of thrombin (k(a)=1.17x10(3)
      M(-1) x s(-1)) and plasmin (k(a)=1.92x10(3) M(-1) x s(-1)). Centerin also bound
      DNA and unfractionated heparin, although there was no functionally significant
      impact on the rate of inhibition. These results suggest that centerin is likely
      to function in vivo in the germinal centre as an efficient inhibitor of a trypsin
      like protease.

PMID- 17447894
TI  - Sirtuins in mammals: insights into their biological function.
AB  - Sirtuins are a conserved family of proteins found in all domains of life. The
      first known sirtuin, Sir2 (silent information regulator 2) of Saccharomyces
      cerevisiae, from which the family derives its name, regulates ribosomal DNA
      recombination, gene silencing, DNA repair, chromosomal stability and longevity.
      Sir2 homologues also modulate lifespan in worms and flies, and may underlie the
      beneficial effects of caloric restriction, the only regimen that slows aging and
      extends lifespan of most classes of organism, including mammals. Sirtuins have
      gained considerable attention for their impact on mammalian physiology, since
      they may provide novel targets for treating diseases associated with aging and
      perhaps extend human lifespan. In this review we describe our current
      understanding of the biological function of the seven mammalian sirtuins, SIRT1
      7, and we will also discuss their potential as mediators of caloric restriction
      and as pharmacological targets to delay and treat human age-related diseases.

PMID- 17447897
TI  - Bnip3 mediates mitochondrial dysfunction and cell death through Bax and Bak.
AB  - Bnip3 is a pro-apoptotic member of the Bcl-2 family that is down-regulated in
      pancreatic cancers, which correlates with resistance to chemotherapy and a
      worsened prognosis. In contrast, Bnip3 is up-regulated in heart failure and
      contributes to loss of myocardial cells during I/R (ischaemia/reperfusion). Bnip3
      exerts its action at the mitochondria, but the mechanism by which Bnip3 mediates
      mitochondrial dysfunction is not clear. In the present study, we have identified
      Bax and Bak as downstream effectors of Bnip3-mediated mitochondrial dysfunction.
      Bnip3 plays a role in hypoxia-mediated cell death, but MEFs (mouse embryonic
      fibroblasts) derived from mice deficient in Bax and Bak were completely resistant
      to hypoxia even with substantial up-regulation of Bnip3. These cells were also
      resistant to Bnip3 overexpression, but re-expression of Bax or Bak restored
      susceptibility to Bnip3, suggesting that Bnip3 can act via either Bax or Bak. In
      contrast, Bnip3 overexpression in wild-type MEFs induced mitochondrial
      dysfunction with loss of membrane potential and release of cytochrome c. Cell
      death by Bnip3 was reduced in the presence of mPTP (mitochondrial permeability
      transition pore) inhibitors, but did not prevent Bnip3-mediated activation of Bax
      or Bak. Moreover, overexpression of Bnip3DeltaTM, a dominant-negative form of
      Bnip3, reduced translocation of GFP (green fluorescent protein)-Bax to
      mitochondria during sI/R (simulated I/R) in HL-1 myocytes. Similarly, down
      regulation of Bnip3 using RNA interference decreased activation of Bax in
      response to sI/R in HL-1 myocytes. These results suggest that Bnip3 mediates
      mitochondrial dysfunction through activation of Bax or Bak which is independent
      of mPTP opening.

PMID- 17447898
TI  - Expression and extracellular release of Trx80, the truncated form of thioredoxin,
      by TNF-alpha- and IL-1beta-stimulated human synoviocytes from patients with
      rheumatoid arthritis.
AB  - Thioredoxin (Trx) plays several important roles, through changes to sulfhydryl
      reactions and protein interactions, in controlling cellular signalling processes
      in RA (rheumatoid arthritis). Trx80, the 10 kDa C-terminal truncated form of Trx,
      is a potent mitogenic cytokine and is involved in the Th1 response. In the
      present study, we have investigated the ability of synoviocytes from five RA
      patients to induce Trx80 after ex vivo stimulation by the pro-inflammatory
      cytokines IL-1beta (interleukin-1beta) and TNF-alpha (tumour necrosis factor
      alpha) or by H(2)O(2). Synoviocytes from five OA (osteoarthritis) patients were
      used as controls. Immunoprecipitation assays using two different antibodies
      showed that RA, but not OA, cells expressed intact Trx80 protein in culture even
      when not stimulated. Treatment with pro-inflammatory cytokines alone or in
      combination enhanced this basal production and induced the extracellular release
      of Trx80 by all of the RA cells tested. Under our experimental conditions, the
      rate of Trx80 release from RA cells was approx. 30% of the total Trx produced. In
      contrast, Trx80 was not detected in response to H(2)O(2) in RA or OA synoviocyte
      lysates and their respective culture supernatants, indicating that the oxidative
      process induced by H(2)O(2) in synoviocytes was unable to modify Trx80 release.
      Moreover, Trx80 induced synoviocyte proliferation as evaluated by [(3)H]thymidine
      incorporation. These results highlight the effect of the inflammatory process on
      the release of both Trx and Trx80 from RA synoviocytes, and suggest that the
      cytokine-induced increase in Trx80 cell release may constitute a link between
      inflammation and the immune system in RA.

PMID- 17447899
TI  - C-reactive protein: a marker or a player?
AB  - It has been suggested that Type 2 diabetes may, in part, be precipitated or
      accelerated by an acute-phase reaction as part of the innate immune response, in
      which large amounts of cytokines are released from adipose tissue, creating a low
      grade inflammatory milieu. There is also firm evidence that atherosclerosis is an
      immune-mediated inflammatory disease. Therefore it is reasonable to imply that
      low-grade inflammation is an important pathogenetic factor in atherosclerosis and
      cardiovascular events in patients with Type 2 diabetes. Over the last few years,
      there have been a lot of promising clinical markers proposed to link inflammation
      and atherosclerosis. Of these markers, hs-CRP (high-sensitivity C-reactive
      protein) might be a prognostic marker for further cardiovascular events, although
      this has been refuted recently. In this issue of Clinical Science, Castoldi and
      co-workers have demonstrated that, in patients with Type 2 diabetes categorized
      into low (<1.0 mg/l), medium (1.0-3.0 mg/l) and high (>3.0 mg/l) hs-CRP groups,
      serum levels of hs-CRP correlated with lipopolysaccharide-stimulated release of
      interleukin-1beta and interleukin-6 in whole blood. This finding may indicate
      that low-grade inflammatory activity might influence cytokine production in these
      patients.

PMID- 17447900
TI  - An inconvenient truth.

PMID- 17447901
TI  - The gas that opens gates: calcium channel activation by ethylene.

PMID- 17447902
TI  - The ins and outs of stable isotopes in plants.

PMID- 17447903
TI  - Rhynie chert: a window into a lost world of complex plant-fungus interactions.

PMID- 17447904
TI  - Small RNAs hit the big time.

PMID- 17447905
TI  - Pollen wall development in flowering plants.
AB  - The outer pollen wall, or exine, is more structurally complex than any other
      plant cell wall, comprising several distinct layers, each with its own
      organizational pattern. Since elucidation of the basic events of pollen wall
      ontogeny using electron microscopy in the 1970s, knowledge of their developmental
      genetics has increased enormously. However, self-assembly processes that are not
      under direct genetic control also play an important role in pollen wall
      patterning. This review integrates ultrastructural and developmental findings
      with recent models for self-assembly in an attempt to understand the origins of
      the morphological complexity and diversity that underpin the science of
      palynology.

PMID- 17447906
TI  - Transporters of ligands for essential metal ions in plants.
AB  - Essential metals are required for healthy plant growth but can be toxic when
      present in excess. Therefore plants have mechanisms of metal homeostasis which
      involve coordination of metal ion transporters for uptake, translocation and
      compartmentalization. However, very little metal in plants is thought to exist as
      free ions. A number of small, organic molecules have been implicated in metal ion
      homeostasis as metal ion ligands to facilitate uptake and transport of metal ions
      with low solubility and also as chelators implicated in sequestration for metal
      tolerance and storage. Ligands for a number of essential metals have been
      identified and proteins involved in the transport of these ligands and of metal
      ligand complexes have been characterized. Here we review recent advances in
      understanding the role of mugineic acid, nicotianamine, organic acids (citrate
      and malate), histidine and phytate as ligands for iron (Fe), zinc (Zn), copper
      (Cu), manganese (Mn) and nickel (Ni) in plants, and the proteins identified as
      their transporters.

PMID- 17447907
TI  - Ethylene activates a plasma membrane Ca(2+)-permeable channel in tobacco
      suspension cells.
AB  - Here, the effects of the ethylene-releasing compound, ethephon, and the ethylene
      precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), on ionic currents across
      plasma membranes and on the cytosolic Ca(2+) activity ([Ca(2+)](c)) of tobacco
      (Nicotiana tabacum) suspension cells were characterized using a patch-clamp
      technique and confocal laser scanning microscopy. Exposure of tobacco protoplasts
      to ethephon and ACC led to activation of a plasma membrane cation channel that
      was permeable to Ba(2+), Mg(2+) and Ca(2+), and inhibited by La(3+), Gd(3+) and
      Al(3+). The ethephon- and ACC-induced Ca(2+)-permeable channel was abolished by
      the antagonist of ethylene perception (1-metycyclopropene) and by the inhibitor
      of ACC synthase (aminovinylglycin), indicating that activation of the Ca(2+)
      permeable channels results from ethylene. Ethephon elicited an increase in the
      [Ca(2+)](c) of tobacco suspension cells, as visualized by the Ca(2+)-sensitive
      probe Fluo-3 and confocal microscopy. The ethephon-induced elevation of
      [Ca(2+)](c) was markedly inhibited by Gd(3+) and BAPTA, suggesting that an influx
      of Ca(2+) underlies the elevation of [Ca(2+)](c). These results indicate that an
      elevation of [Ca(2+)](c), resulting from activation of the plasma membrane Ca(2+)
      permeable channels by ethylene, is an essential component in ethylene signaling
      in plants.

PMID- 17447908
TI  - Evolutionary control of leaf element composition in plants.
AB  - Leaf nitrogen (N) and phosphorus (P) concentrations are correlated in plants.
      Higher-level phylogenetic effects can influence leaf N and P. By contrast, little
      is known about the phylogenetic variation in the leaf accumulation of most other
      elements in plant tissues, including elements with quantitatively lesser roles in
      metabolism than N, and elements that are nonessential for plant growth. Here the
      leaf composition of 42 elements is reported from a statistically unstructured
      data set comprising over 2000 leaf samples, representing 670 species and 138
      families of terrestrial plants. Over 25% of the total variation in leaf element
      composition could be assigned to the family level and above for 21 of these
      elements. The remaining variation corresponded to differences between species
      within families, to differences between sites which were likely to be caused by
      soil and climatic factors, and to variation caused by sampling techniques. While
      the majority of variation in leaf mineral composition is undoubtedly associated
      with nonevolutionary factors, identifying higher-level phylogenetic variation in
      leaf elemental composition increases our understanding of terrestrial nutrient
      cycles and the transfer of toxic elements from soils to living organisms.
      Identifying mechanisms by which different plant families control their leaf
      elemental concentration remains a challenge.

PMID- 17447909
TI  - Identification of hyperpolarization-activated calcium channels in apical pollen
      tubes of Pyrus pyrifolia.
AB  - The pollen tube has been widely used to study the mechanisms underlying polarized
      tip growth in plants. A steep tip-to-base gradient of free cytosolic calcium
      ([Ca(2+)](cyt)) is essential for pollen-tube growth. Local Ca(2+) influx mediated
      by Ca(2+)-permeable channels plays a key role in maintaining this [Ca(2+)](cyt)
      gradient. Here, we developed a protocol for successful isolation of spheroplasts
      from pollen tubes of Pyrus pyrifolia and identified a hyperpolarization-activated
      cation channel using the patch-clamp technique. We showed that the cation channel
      conductance displayed a strong selectivity for divalent cations, with a relative
      permeability sequence of barium (Ba(2+)) approximately Ca(2+) > magnesium
      (Mg(2+)) > strontium (Sr(2+)) > manganese (Mn(2+)). This channel conductance was
      selective for Ca(2+) over chlorine (Cl(-)) (relative permeability P(Ca)/P(Cl) =
      14 in 10 mm extracellular Ca(2+)). We also showed that the channel was inhibited
      by the Ca(2+) channel blockers lanthanum (La(3+)) and gadolinium (Gd(3+)).
      Furthermore, channel activity depended on extracellular pH and pollen viability.
      We propose that the Ca(2+)-permeable channel is likely to play a role in
      mediating Ca(2+) influx into the growing pollen tubes to maintain the
      [Ca(2+)](cyt) gradient.

PMID- 17447910
TI  - Organ-specific, developmental, hormonal and stress regulation of expression of
      putative pectate lyase genes in Arabidopsis.
AB  - Pectate lyases catalyse the eliminative cleavage of de-esterified
      homogalacturonan in pectin, a major component of the primary cell walls in higher
      plants. In the completed genome of Arabidopsis, there are 26 genes (AtPLLs) that
      encode pectate lyase-like proteins. Here, we analysed the expression pattern of
      all AtPLLs in different organs, at different stages of seedling development and
      in response to various hormones and stresses. The expression of PLLs varied
      considerably in different organs, with no expression of some PLLs in vegetative
      organs. Interestingly, all PLL genes are expressed in flowers. Several PLLs are
      expressed highly in pollen, suggesting a role for these in pollen development
      and/or function. Analysis of expression of all PLL genes in seedlings treated
      with hormones, abiotic stresses and elicitors of defense responses revealed
      significant changes in the expression of some PLLs without affecting the other
      PLLs. The stability of transcripts of PLLs varied considerably among different
      genes. Our results indicate a complex regulation of expression of PLLs and
      involvement of PLLs in some of the hormonal and stress responses.

PMID- 17447911
TI  - A class I KNOX gene from the palm species Elaeis guineensis (Arecaceae) is
      associated with meristem function and a distinct mode of leaf dissection.
AB  - Class I Knotted-like homeobox (KNOX) transcription factors are important
      regulators of shoot apical meristem function and leaf morphology by their
      contribution to dissected leaf development. Palms are of particular interest as
      they produce dissected leaves generated by a distinct mechanism compared with
      eudicots. The question addressed here was whether class I KNOX genes might be
      involved in meristem function and leaf dissection in palms. Here, we
      characterized the EgKNOX1 gene from oil palm (Elaeis guineensis, Arecaceae) and
      compared it with available sequences from other plant species using phylogenetic
      analysis. Gene expression pattern was investigated using reverse transcription
      polymerase chain reaction (RT-PCR) and in situ hybridization. Functional analysis
      was carried out by ectopic expression in Arabidopsis and rice. EgKNOX1 was
      orthologous to STM from Arabidopsis and to OSH1 from rice. It was expressed in
      the central zone of both vegetative and reproductive meristems. During leaf
      development, its expression was associated with plications from which the
      leaflets originate. Different modes of leaf dissection are seen to involve a
      similar class of genes to control meristematic activities, which govern the
      production of dissected morphologies.

PMID- 17447912
TI  - High accumulation of soluble sugars in deep supercooling Japanese white birch
      xylem parenchyma cells.
AB  - Seasonal changes in the accumulation of soluble sugars in extracellular freezing
      cortical parenchyma cells and deep supercooling xylem parenchyma cells in
      Japanese white birch (Betula platyphylla var. japonica) were compared to identify
      the effects of soluble sugars on the mechanism of deep supercooling, which keeps
      the liquid state of water in cells under extremely low temperatures for long
      periods. Soluble sugars in both tissues were analyzed by high-performance liquid
      chromatography (HPLC), and the concentrations of sugars in cells were estimated
      by histological observation of occupancy rates of parenchyma cells in each
      tissue. Relative and equilibrium melting points of parenchyma cells were measured
      by differential thermal analysis and cryoscanning electron microscopy,
      respectively. In both xylem and cortical parenchyma cells, amounts of sucrose,
      raffinose and stachyose increased in winter, but amounts of fructose and glucose
      exhibited little change throughout the entire year. In addition, no sugars were
      found to be specific for either tissue. Combined results of HPLC analyses,
      histological observation and melting point analyses confirmed that the
      concentration of sugars was much higher in xylem cells than in cortical cells. It
      is thought that the higher concentration of soluble sugars in xylem cells may
      contribute to facilitation of deep supercooling in xylem cells by depressing the
      nucleation temperature.

PMID- 17447913
TI  - A quantitative trait loci analysis of zinc hyperaccumulation in Arabidopsis
      halleri.
AB  - The mechanisms of metal hyperaccumulation are still not understood, so we
      conducted a quantitative trait locus (QTL) analysis of zinc (Zn)
      hyperaccumulation in Arabidopsis halleri, in a cross between this and its sister
      species, A. petraea, in order to determine the number and approximate location of
      the genomic regions significantly contributing to this adaptation. An F2 cross
      between the two species was made, and the leaf Zn concentration of 92 individuals
      was measured at both low (10 microm) and high (100 microm) Zn concentrations.
      Twenty-five markers were established that were distributed on all of the eight
      chromosomes. Mapping of the markers established that they were essentially
      collinear with previous studies. QTLs exceeding a logarithm to the base 10 of the
      odds (LOD) value of 3 were found on chromosomes 4 (low Zn), 6 (high Zn) and 7
      (both high and low Zn). Evidence for a QTL on chromosome 3 (low Zn) was also
      found. This analysis validates a previously used method of QTL analysis, based on
      microarray analysis of segregating families. Genes that have altered during the
      evolution of this character should also be QTL: this analysis calls into question
      a number of candidate genes from consideration as such primary genes because they
      do not appear to be associated with QTLs.

PMID- 17447914
TI  - Elevated atmospheric CO(2) concentration and diurnal cycle induce changes in
      lipid composition in Arabidopsis thaliana.
AB  - Few studies regarding the effects of elevated atmospheric CO(2) concentrations on
      plant lipid metabolism have been carried out. Here, the effects of elevated CO(2)
      concentration on lipid composition in mature seeds and in leaves during the
      diurnal cycle of Arabidopsis thaliana were investigated. Plants were grown in
      controlled climate chambers at elevated (800 ppm) and ambient CO(2)
      concentrations. Lipids were extracted and characterized using thin layer
      chromatography (TLC) and gas liquid chromatography. The fatty acid profile of
      total leaf lipids showed large diurnal variations. However, the elevated CO(2)
      concentration did not induce any significant differences in the diurnal pattern
      compared with the ambient concentration. The major chloroplast lipids
      monogalactosyldiacylglycerol (MGDG) and phosphatidylglycerol (PG) were decreased
      at elevated CO(2) in favour of phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE). Elevated CO(2) produced a 25% lower ratio of
      16:1trans to 16:0 in PG compared with the ambient concentration. With good
      nutrient supply, growth at elevated CO(2) did not significantly affect single
      seed weight, total seed mass, oil yield per seed, or the fatty acid profile of
      the seeds. This study has shown that elevated CO(2) induced changes in leaf lipid
      composition in A. thaliana, whereas seed lipids were unaffected.

PMID- 17447915
TI  - Oxygen isotope enrichment of organic matter in Ricinus communis during the diel
      course and as affected by assimilate transport.
AB  - The oxygen isotope composition in leaf water and organic compounds in different
      plant tissues is useful for assessing the physiological performance of plants in
      their environment, but more information is needed on Delta(18)O variation during
      a diel course. Here, we assessed Delta(18)O of the organic matter in leaves,
      phloem and xylem in stem segments, and fine roots of Ricinus communis during a
      full diel cycle. Enrichment of newly assimilated organic matter in equilibrium
      with leaf water was calculated by applying a nonsteady-state evaporative
      enrichment model. During the light period, Delta(18)O of the water soluble
      organic matter pool in leaves and phloem could be explained by a 27 per thousand
      enrichment compared with leaf water enrichment. Leaf water enrichment influenced
      Delta(18)O of phloem organic matter during the night via daytime starch synthesis
      and night-time starch remobilization. Phloem transport did not affect Delta(18)O
      of phloem organic matter. Diel variation in Delta(18)O in organic matter pools
      can be modeled, and oxygen isotopic information is not biased during transport
      through the plant. These findings will aid field studies that characterize
      environmental influences on plant water balance using Delta(18)O in phloem
      organic matter or tree rings.

PMID- 17447916
TI  - Leaf- and stand-level responses of a forested mesocosm to independent
      manipulations of temperature and vapor pressure deficit.
AB  - Alterations in temperature (T) and vapor pressure deficit (VPD) strongly
      influence gas exchange, but because VPD is highly influenced by T, the effects of
      these two factors are difficult to separate. Here, the concomitant effects of T
      and VPD on CO(2) uptake, stomatal conductance, and transpiration at leaf- and
      canopy-levels were examined for a stand of trees (Populus deltoides) enclosed
      within large mesocosms. T and VPD were independently altered to yield a factorial
      combination of treatments of low (24 degrees C) or high (30 degrees C) T and low
      (0.75) or high (1.75 kPa) VPD. Traditional leaf-level gas exchange measurements
      were compared with whole-canopy exchange to verify typical scaling methods.
      Elevated T resulted in an average 40% and 14% increase in midday leaf-level and
      canopy-level net CO(2) uptake, respectively. Other physiological responses to
      elevated T and VPD were similar at both scales, but the magnitude of change was
      usually less pronounced at the canopy-level. Surprisingly, only minimal
      interactions between T and VPD were found to influence responses of CO(2) uptake
      and stomatal conductance at either level.

PMID- 17447917
TI  - Predicting the limits to tree height using statistical regressions of leaf
      traits.
AB  - Leaf morphology and physiological functioning demonstrate considerable plasticity
      within tree crowns, with various leaf traits often exhibiting pronounced vertical
      gradients in very tall trees. It has been proposed that the trajectory of these
      gradients, as determined by regression methods, could be used in conjunction with
      theoretical biophysical limits to estimate the maximum height to which trees can
      grow. Here, we examined this approach using published and new experimental data
      from tall conifer and angiosperm species. We showed that height predictions were
      sensitive to tree-to-tree variation in the shape of the regression and to the
      biophysical endpoints selected. We examined the suitability of proposed end
      points and their theoretical validity. We also noted that site and environment
      influenced height predictions considerably. Use of leaf mass per unit area or
      leaf water potential coupled with vulnerability of twigs to cavitation poses a
      number of difficulties for predicting tree height. Photosynthetic rate and carbon
      isotope discrimination show more promise, but in the second case, the complex
      relationship between light, water availability, photosynthetic capacity and
      internal conductance to CO(2) must first be characterized.

PMID- 17447918
TI  - Role of hydrogen peroxide during the interaction between the hemibiotrophic
      fungal pathogen Septoria tritici and wheat.
AB  - Hydrogen peroxide (H(2)O(2)) is reported to inhibit biotrophic but benefit
      necrotrophic pathogens. Infection by necrotrophs can result in a massive
      accumulation of H(2)O(2) in hosts. Little is known of how pathogens with both
      growth types are affected (hemibiotrophs). The hemibiotroph, Septoria tritici,
      infecting wheat (Triticum aestivum) is inhibited by H(2)O(2) during the
      biotrophic phase, but a large H(2)O(2) accumulation occurs in the host during
      reproduction. Here, we infiltrated catalase, H(2)O(2) or water into wheat during
      the biotrophic or the necrotrophic phase of S. tritici and studied the effect of
      infection on host physiology to get an understanding of the survival strategy of
      the pathogen. H(2)O(2) removal by catalase at both early and late stages made
      plants more susceptible, whereas H(2)O(2) made them more resistant. H(2)O(2) is
      harmful to S. tritici throughout its life cycle, but it can be tolerated. The
      late accumulation of H(2)O(2) is unlikely to result from down-regulation of
      photosynthesis, but probably originates from damage to the peroxisomes during the
      general tissue collapse, which is accompanied by release of soluble sugars in a
      susceptible cultivar.

PMID- 17447919
TI  - Fungal endophytes in a 400-million-yr-old land plant: infection pathways, spatial
      distribution, and host responses.
AB  - The Early Devonian Rhynie chert has been critical in documenting early land plant
      fungal interactions. However, complex associations involving several fungi that
      enter into qualitatively different relationships with a single host plant and
      even interact with one another have not yet been detailed. Here, we studied
      petrographic thin sections of the Rhynie chert plant Nothia aphylla. Three fungal
      endophytes (co)occur in prostrate axes of this plant: narrow hyphae producing
      clusters of small spores; large spherical spores/zoosporangia; and wide aseptate
      hyphae that form intercellular vesicles in the cortex. Host responses on attack
      include bulging of infected rhizoids, formation of encasement layers around
      intracellular hyphae, and separation of infected from uninfected tissues by
      secondarily thickened cell walls. A complex simultaneous interaction of N.
      aphylla with three endophytic fungi was discovered. The host responses indicate
      that some of the mechanisms causing host responses in extant plants were in place
      400 million yr ago. Anatomical and life history features of N. aphylla suggest
      that this plant may have been particularly susceptible to colonization by fungi.

PMID- 17447920
TI  - Transcription activity of rRNA genes correlates with a tendency towards
      intergenomic homogenization in Nicotiana allotetraploids.
AB  - This paper establishes relationships between two aspects of ribosomal DNA (rDNA)
      biology: epigenetic silencing of rDNA loci; and homogenization leading to
      concerted evolution. Here, we examined rDNA inheritance and expression patterns
      in three natural Nicotiana allopolyploids (closest living descendants of diploid
      parents are given), N. rustica (N. paniculata x N. undulata), N. tabacum (N.
      sylvestris x N. tomentosiformis) and N. arentsii (N. undulata x N. wigandioides),
      and synthetic F(1) hybrids and allopolyploids. The extent of interlocus rDNA
      homogenization decreased in the direction N. arentsii > N. tabacum > N. rustica.
      The persistence of parental rDNA units in one of the subgenomes was associated
      with their transcription inactivity and likely heterochromatization. Of synthetic
      hybrids and polyploids only N. paniculata x N. undulata showed strong uniparental
      transcriptional silencing of rDNA triggered already in F(1). Epigenetic patterns
      of expression established early in allopolyploid nucleus formation may render
      units susceptible or resistant to homogenization over longer time-frames. We
      propose that nucleolus-associated transcription leaves rDNA units vulnerable to
      homogenization, while epigenetically inactivated units, well-separated from the
      nucleolus, remain unconverted.

PMID- 17447921
TI  - Chromosomal stasis in diploids contrasts with genome restructuring in auto- and
      allopolyploid taxa of Hepatica (Ranunculaceae).
AB  - Polyploidization and chromosomal rearrangements are recognized as major forces in
      plant evolution. Their role is investigated in the disjunctly distributed
      northern hemisphere Hepatica (Ranunculaceae). Chromosome numbers, karyotype
      morphology, banding patterns, 5S and 35S rDNA localization in all known species
      were investigated and interpreted in a phylogenetic context established from
      nuclear internal transcribed spacer (ITS) and plastid matK sequences. All species
      had a chromosome base number of x = 7. The karyotype was symmetric and showed
      little variation among diploids with one locus each of 5S and 35S rDNA, except
      for interpopulational variation concerning 35S rDNA loci number and localization
      in H. asiatica. Tetraploids exhibited chromosomal changes, including asymmetry
      and/or loss of rDNA loci. Nuclear and plastid sequences resulted in incongruent
      topologies because of the positions of some tetraploid taxa. The diversification
      of Hepatica occurred not earlier than the Pliocene. Genome restructuring,
      especially involving 35S rDNA, within a few million yr or less characterizes
      evolution of both auto- and allopolyploids and of the diploid species H.
      asiatica, which is the presumptive ancestor of two other diploid species.

PMID- 17447922
TI  - Conceptual analysis of methods applied to assessment of diversity within and
      distance between populations with asexual or mixed mode of reproduction.
AB  - Measures of diversity within populations, and distance between populations, are
      compared for organisms with an asexual or mixed mode of reproduction. Examples
      are drawn from studies of plant pathogenic fungi based on binary traits including
      presence/absence of DNA bands or virulence/avirulence to differential hosts.
      Commonly used measures of population diversity or genetic distance consider
      either genotype frequencies or allele frequencies. Kosman's diversity and
      distance measures are the most suitable for populations with an asexual or mixed
      mode of reproduction, because by considering genetic patterns of all individuals
      they take into account not just the genotype frequencies but also the genetic
      similarities between genotypes in the populations. The Kosman distance and
      diversity measures for populations can be calculated using different measures of
      dissimilarity between individuals (the simple mismatch, Jaccard and Dice
      coefficients of dissimilarity). Kosman's distances based on the simple mismatch
      and Jaccard dissimilarities are metrics. Comparisons of diversity indices for
      hypothetical examples as well as for actual data sets are presented to
      demonstrate that inferences from diversity analysis of populations can be driven
      by techniques of diversity and distance assessments and not only data driven.

PMID- 17447923
TI  - A method for extracting plant roots from soil which facilitates rapid sample
      processing without compromising measurement accuracy.
AB  - This study evaluates a novel method for extracting roots from soil samples and
      applies it to estimate standing crop root mass (+/- confidence intervals) in an
      eastern Amazon rainforest. Roots were manually extracted from soil cores over a
      period of 40 min, which was split into 10 min time intervals. The pattern of
      cumulative extraction over time was used to predict root extraction beyond 40
      min. A maximum-likelihood approach was used to calculate confidence intervals.
      The temporal prediction method added 21-32% to initial estimates of standing crop
      root mass. According to predictions, complete manual root extraction from 18
      samples would have taken c. 239 h, compared with 12 h using the prediction
      method. Uncertainties (percentage difference between mean, and 10th and 90th
      percentiles) introduced by the prediction method were small (12-15%), compared
      with uncertainties caused by spatial variation in root mass (72-191%, for nine
      samples per plot surveyed). This method provides a way of increasing the number
      of root samples processed per unit time, without compromising measurement
      accuracy.

PMID- 17447924
TI  - Our future as history.
AB  - These are exciting and challenging times for the International Biometric Society
      and professional societies in general. These challenges require that we actively
      plan for our future and consider "Our Future as History"; that which lies ahead
      becomes the present and the present becomes history. To plan for the future I
      build on themes identified in my presidential address in Montreal, outlining our
      current status and initiatives, predicting and highlighting implications that
      call for expansion of our current activities and creation of new ones. These will
      ensure that we create our desired future and thereby produce a proud legacy.

PMID- 17447925
TI  - Mixture modeling for genome-wide localization of transcription factors.
AB  - Chromatin immunoprecipitation followed by DNA microarray analysis (ChIP-chip
      methodology) is an efficient way of mapping genome-wide protein-DNA interactions.
      Data from tiling arrays encompass DNA-protein interaction measurements on
      thousands or millions of short oligonucleotides (probes) tiling a whole
      chromosome or genome. We propose a new model-based method for analyzing ChIP-chip
      data. The proposed model is motivated by the widely used two-component
      multinomial mixture model of de novo motif finding. It utilizes a hierarchical
      gamma mixture model of binding intensities while incorporating inherent spatial
      structure of the data. In this model, genomic regions belong to either one of the
      following two general groups: regions with a local protein-DNA interaction (peak)
      and regions lacking this interaction. Individual probes within a genomic region
      are allowed to have different localization rates accommodating different binding
      affinities. A novel feature of this model is the incorporation of a distribution
      for the peak size derived from the experimental design and parameters. This leads
      to the relaxation of the fixed peak size assumption that is commonly employed
      when computing a test statistic for these types of spatial data. Simulation
      studies and a real data application demonstrate good operating characteristics of
      the method including high sensitivity with small sample sizes when compared to
      available alternative methods.

PMID- 17447926
TI  - A modified Bayes information criterion with applications to the analysis of
      comparative genomic hybridization data.
AB  - In the analysis of data generated by change-point processes, one critical
      challenge is to determine the number of change-points. The classic Bayes
      information criterion (BIC) statistic does not work well here because of
      irregularities in the likelihood function. By asymptotic approximation of the
      Bayes factor, we derive a modified BIC for the model of Brownian motion with
      changing drift. The modified BIC is similar to the classic BIC in the sense that
      the first term consists of the log likelihood, but it differs in the terms that
      penalize for model dimension. As an example of application, this new statistic is
      used to analyze array-based comparative genomic hybridization (array-CGH) data.
      Array-CGH measures the number of chromosome copies at each genome location of a
      cell sample, and is useful for finding the regions of genome deletion and
      amplification in tumor cells. The modified BIC performs well compared to existing
      methods in accurately choosing the number of regions of changed copy number.
      Unlike existing methods, it does not rely on tuning parameters or intensive
      computing. Thus it is impartial and easier to understand and to use.

PMID- 17447927
TI  - Inferring the location of tumor suppressor genes by modeling frequency of allelic
      loss.
AB  - Allelic loss is often part of a multistep process leading to tumorigenesis.
      Analysis of genomic markers highlights regions of elevated allelic loss, which in
      turn suggests a nearby tumor suppressor. Furthermore, pooling published analyses
      to combine evidence can increase the power to detect a tumor suppressor gene. If
      the pattern of loss for each tumor, or allelotype, is known, a stochastic model
      proposed by Newton et al. (1998, Statistics in Medicine 17, 1425-1445) can be
      used to analyze the correlated binary data. Many studies report only incomplete
      allelotypes, augmented with frequencies of allelic loss (FAL) at each marker, in
      which the number of informative tumors showing allelic loss is provided along
      with the number of informative tumors. We describe an extension of the allelotype
      model to handle FAL data, using a hidden Markov model or a normal approximation
      to compute the likelihood. The FAL model is illustrated using data from a study
      of colorectal cancer.

PMID- 17447928
TI  - Assessing differential gene expression with small sample sizes in oligonucleotide
      arrays using a mean-variance model.
AB  - The identification of the genes that are differentially expressed in two-sample
      microarray experiments remains a difficult problem when the number of arrays is
      very small. We discuss the implications of using ordinary t-statistics and
      examine other commonly used variants. For oligonucleotide arrays with multiple
      probes per gene, we introduce a simple model relating the mean and variance of
      expression, possibly with gene-specific random effects. Parameter estimates from
      the model have natural shrinkage properties that guard against inappropriately
      small variance estimates, and the model is used to obtain a differential
      expression statistic. A limiting value to the positive false discovery rate
      (pFDR) for ordinary t-tests provides motivation for our use of the data structure
      to improve variance estimates. Our approach performs well compared to other
      proposed approaches in terms of the false discovery rate.

PMID- 17447929
TI  - Enhanced quantile normalization of microarray data to reduce loss of information
      in gene expression profiles.
AB  - In microarray experiments, removal of systematic variations resulting from array
      preparation or sample hybridization conditions is crucial to ensure sensible
      results from the ensuing data analysis. For example, quantile normalization is
      routinely used in the treatment of both oligonucleotide and cDNA microarray data,
      even though there might be some loss of information in the normalization process.
      We recognize that the ideal normalization, if it ever exists, would aim to keep
      the maximal amount of gene profile information with the lowest possible noise.
      With this objective in mind, we propose a valuable enhancement to quantile
      normalization, and demonstrate through three Affymetrix experiments that the
      enhanced normalization can result in better performance in detecting and ranking
      differentially expressed genes across experimental conditions.

PMID- 17447930
TI  - Joint modeling of progression of HIV resistance mutations measured with
      uncertainty and failure time data.
AB  - Development of HIV resistance mutations is a major cause for failure of
      antiretroviral treatment. This article proposes a method for jointly modeling the
      processes of viral genetic changes and treatment failure. Because the viral
      genome is measured with uncertainty, a hidden Markov model is used to fit the
      viral genetic process. The uncertain viral genotype is included as a time
      dependent covariate in a Cox model for failure time, and an expectation
      maximization algorithm is used to estimate the model parameters. This model
      allows simultaneous evaluation of the sequencing uncertainty and the effect of
      resistance mutation on the risk of virological and immunological failures.
      Various model checking tests are provided to assess the appropriateness of the
      model. Simulation studies are performed to investigate the finite-sample
      properties of the proposed methods, which are then applied to data collected in
      three phase II clinical trials testing antiretroviral treatments containing the
      drug efavirenz.

PMID- 17447931
TI  - On robustness and model flexibility in survival analysis: transformed hazard
      models and average effects.
AB  - Yin and Ibrahim (2005a, Biometrics 61, 208-216) use a Box-Cox transformed hazard
      model to acknowledge uncertainty about how a linear predictor acts upon the
      hazard function of a failure-time response. Particularly, additive and
      proportional hazards models arise for particular values of the transformation
      parameter. As is often the case, however, this added model flexibility is
      obtained at the cost of lessened parameter interpretability. Particularly, the
      interpretation of the coefficients in the linear predictor is intertwined with
      the value of the transformation parameter. Moreover, some data sets contain very
      little information about this parameter. To shed light on the situation, we
      consider average effects based on averaging (over the joint distribution of the
      explanatory variables and the failure-time response) the partial derivatives of
      the hazard, or the log-hazard, with respect to the explanatory variables. First,
      we consider fitting models which do assume a particular form of covariate
      effects, for example, proportional hazards or additive hazards. In some such
      circumstances, average effects are seen to be inferential targets which are
      robust to the effect form being misspecified. Second, we consider average effects
      as targets of inference when using the transformed hazard model. We show that in
      addition to being more interpretable inferential targets, average effects can
      sometimes be estimated more efficiently than the corresponding regression
      coefficients.

PMID- 17447932
TI  - Semiparametric analysis of correlated recurrent and terminal events.
AB  - In clinical and observational studies, recurrent event data (e.g.,
      hospitalization) with a terminal event (e.g., death) are often encountered. In
      many instances, the terminal event is strongly correlated with the recurrent
      event process. In this article, we propose a semiparametric method to jointly
      model the recurrent and terminal event processes. The dependence is modeled by a
      shared gamma frailty that is included in both the recurrent event rate and
      terminal event hazard function. Marginal models are used to estimate the
      regression effects on the terminal and recurrent event processes, and a Poisson
      model is used to estimate the dispersion of the frailty variable. A sandwich
      estimator is used to achieve additional robustness. An analysis of
      hospitalization data for patients in the peritoneal dialysis study is presented
      to illustrate the proposed method.

PMID- 17447933
TI  - Bayesian semiparametric proportional odds models.
AB  - Methodology for implementing the proportional odds regression model for survival
      data assuming a mixture of finite Polya trees (MPT) prior on baseline survival is
      presented. Extensions to frailties and generalized odds rates are discussed.
      Although all manner of censoring and truncation can be accommodated, we discuss
      model implementation, regression diagnostics, and model comparison for right
      censored data. An advantage of the MPT model is the relative ease with which
      predictive densities, survival, and hazard curves are generated. Much discussion
      is devoted to practical implementation of the proposed models, and a novel MCMC
      algorithm based on an approximating parametric normal model is developed. A
      modest simulation study comparing the small sample behavior of the MPT model to a
      rank-based estimator and a real data example is presented.

PMID- 17447934
TI  - Regression modeling of semicompeting risks data.
AB  - Semicompeting risks data are often encountered in clinical trials with
      intermediate endpoints subject to dependent censoring from informative dropout.
      Unlike with competing risks data, dropout may not be dependently censored by the
      intermediate event. There has recently been increased attention to these data, in
      particular inferences about the marginal distribution of the intermediate event
      without covariates. In this article, we incorporate covariates and formulate
      their effects on the survival function of the intermediate event via a functional
      regression model. To accommodate informative censoring, a time-dependent copula
      model is proposed in the observable region of the data which is more flexible
      than standard parametric copula models for the dependence between the events. The
      model permits estimation of the marginal distribution under weaker assumptions
      than in previous work on competing risks data. New nonparametric estimators for
      the marginal and dependence models are derived from nonlinear estimating
      equations and are shown to be uniformly consistent and to converge weakly to
      Gaussian processes. Graphical model checking techniques are presented for the
      assumed models. Nonparametric tests are developed accordingly, as are inferences
      for parametric submodels for the time-varying covariate effects and copula
      parameters. A novel time-varying sensitivity analysis is developed using the
      estimation procedures. Simulations and an AIDS data analysis demonstrate the
      practical utility of the methodology.

PMID- 17447935
TI  - A spatial scan statistic for survival data.
AB  - Spatial scan statistics with Bernoulli and Poisson models are commonly used for
      geographical disease surveillance and cluster detection. These models, suitable
      for count data, were not designed for data with continuous outcomes. We propose a
      spatial scan statistic based on an exponential model to handle either uncensored
      or censored continuous survival data. The power and sensitivity of the developed
      model are investigated through intensive simulations. The method performs well
      for different survival distribution functions including the exponential, gamma,
      and log-normal distributions. We also present a method to adjust the analysis for
      covariates. The cluster detection method is illustrated using survival data for
      men diagnosed with prostate cancer in Connecticut from 1984 to 1995.

PMID- 17447936
TI  - A class of multiplicity adjusted tests for spatial clustering based on case
      control point data.
AB  - A class of tests with quadratic forms for detecting spatial clustering of health
      events based on case-control point data is proposed. It includes Cuzick and
      Edwards's test statistic (1990, Journal of the Royal Statistical Society, Series
      B 52, 73-104). Although they used the property of asymptotic normality of the
      test statistic, we show that such an approximation is generally poor for
      moderately large sample sizes. Instead, we suggest a central chi-square
      distribution as a better approximation to the asymptotic distribution of the test
      statistic. Furthermore, not only to estimate the optimal value of the unknown
      parameter on the scale of cluster but also to adjust for multiple testing due to
      repeating the procedure by changing the parameter value, we propose the minimum
      of the profile p-value of the test statistic for the parameter as an integrated
      test statistic. We also provide a statistic to estimate the areas or cases which
      make large contributions to significant clustering. The proposed methods are
      illustrated with a data set concerning the locations of cases of childhood
      leukemia and lymphoma and another on early medieval grave site locations
      consisting of affected and nonaffected grave sites.

PMID- 17447937
TI  - Hierarchical models for combining ecological and case-control data.
AB  - The ecological study design suffers from a broad range of biases that result from
      the loss of information regarding the joint distribution of individual-level
      outcomes, exposures, and confounders. The consequent nonidentifiability of
      individual-level models cannot be overcome without additional information; we
      combine ecological data with a sample of individual-level case-control data. The
      focus of this article is hierarchical models to account for between-group
      heterogeneity. Estimation and inference pose serious computational challenges. We
      present a Bayesian implementation based on a data augmentation scheme where the
      unobserved data are treated as auxiliary variables. The methods are illustrated
      with a dataset of county-specific infant mortality data from the state of North
      Carolina.

PMID- 17447938
TI  - Linear measurement error models with restricted sampling.
AB  - The relationship between nutrient consumption and chronic disease risk is the
      focus of a large number of epidemiological studies where food frequency
      questionnaires (FFQ) and food records are commonly used to assess dietary intake.
      However, these self-assessment tools are known to involve substantial random
      error for most nutrients, and probably important systematic error as well. Study
      subject selection in dietary intervention studies is sometimes conducted in two
      stages. At the first stage, FFQ-measured dietary intakes are observed and at the
      second stage another instrument, such as a 4-day food record, is administered
      only to participants who have fulfilled a prespecified criterion that is based on
      the baseline FFQ-measured dietary intake (e.g., only those reporting percent
      energy intake from fat above a prespecified quantity). Performing analysis
      without adjusting for this truncated sample design and for the measurement error
      in the nutrient consumption assessments will usually provide biased estimates for
      the population parameters. In this work we provide a general statistical analysis
      technique for such data with the classical additive measurement error that
      corrects for the two sources of bias. The proposed technique is based on multiple
      imputation for longitudinal data. Results of a simulation study along with a
      sensitivity analysis are presented, showing the performance of the proposed
      method under a simple linear regression model.

PMID- 17447939
TI  - Logistic regression with exposure biomarkers and flexible measurement error.
AB  - Regression calibration, refined regression calibration, and conditional scores
      estimation procedures are extended to a measurement model that is motivated by
      nutritional and physical activity epidemiology. Biomarker data, available on a
      small subset of a study cohort for reasons of cost, are assumed to adhere to a
      classical measurement error model, while corresponding self-report nutrient
      consumption or activity-related energy expenditure data are available for the
      entire cohort. The self-report assessment measurement model includes a person
      specific random effect, the mean and variance of which may depend on individual
      characteristics such as body mass index or ethnicity. Logistic regression is used
      to relate the disease odds ratio to the actual, but unmeasured, dietary or
      physical activity exposure. Simulation studies are presented to evaluate and
      contrast the three estimation procedures, and to provide insight into preferred
      biomarker subsample size under selected cohort study configurations.

PMID- 17447940
TI  - Model checking for ROC regression analysis.
AB  - The receiver operating characteristic (ROC) curve is a prominent tool for
      characterizing the accuracy of a continuous diagnostic test. To account for
      factors that might influence the test accuracy, various ROC regression methods
      have been proposed. However, as in any regression analysis, when the assumed
      models do not fit the data well, these methods may render invalid and misleading
      results. To date, practical model-checking techniques suitable for validating
      existing ROC regression models are not yet available. In this article, we develop
      cumulative residual-based procedures to graphically and numerically assess the
      goodness of fit for some commonly used ROC regression models, and show how
      specific components of these models can be examined within this framework. We
      derive asymptotic null distributions for the residual processes and discuss
      resampling procedures to approximate these distributions in practice. We
      illustrate our methods with a dataset from the cystic fibrosis registry.

PMID- 17447941
TI  - Nonparametric estimation of the concordance correlation coefficient under
      univariate censoring.
AB  - Assessing agreement is often of interest in clinical studies to evaluate the
      similarity of measurements produced by different raters or methods on the same
      subjects. Lin's (1989, Biometrics 45, 255-268) concordance correlation
      coefficient (CCC) has become a popular measure of agreement for correlated
      continuous outcomes. However, commonly used estimation methods for the CCC do not
      accommodate censored observations and are, therefore, not applicable for survival
      outcomes. In this article, we estimate the CCC nonparametrically through the
      bivariate survival function. The proposed estimator of the CCC is proven to be
      strongly consistent and asymptotically normal, with a consistent bootstrap
      variance estimator. Furthermore, we propose a time-dependent agreement
      coefficient as an extension of Lin's (1989) CCC for measuring the agreement
      between survival times among subjects who survive beyond a specified time point.
      A nonparametric estimator is developed for the time-dependent agreement
      coefficient as well. It has the same asymptotic properties as the estimator of
      the CCC. Simulation studies are conducted to evaluate the performance of the
      proposed estimators. A real data example from a prostate cancer study is used to
      illustrate the method.

PMID- 17447942
TI  - The continual reassessment method for multiple toxicity grades: a Bayesian quasi
      likelihood approach.
AB  - We consider the case of phase I trials for treatment of cancer or other severe
      diseases in which grade information is available about the severity of toxicity.
      Most dose allocation procedures dichotomize toxicity grades based on being dose
      limiting, which may not work well for severe and possibly irreversible toxicities
      such as renal, liver, and neurological toxicities, or toxicities with long
      duration. We propose a simple extension to the continual reassessment method
      (CRM), called the Quasi-CRM, to incorporate grade information. Toxicity grades
      are first converted to numeric scores that reflect their impacts on the dose
      allocation procedure, and then incorporated into the CRM using the quasi
      Bernoulli likelihood. A simulation study demonstrates that the Quasi-CRM is
      superior to the standard CRM and comparable to a univariate version of the Bekele
      and Thall method (2004, Journal of the American Statistical Association 99, 26
      35). We also present sensitivity analysis of the new method with respect to
      toxicity scores, and discuss practical issues such as extending the simple
      algorithmic up-and-down designs.

PMID- 17447943
TI  - Surrogate marker evaluation from an information theory perspective.
AB  - The last 20 years have seen lots of work in the area of surrogate marker
      validation, partly devoted to frame the evaluation in a multitrial framework,
      leading to definitions in terms of the quality of trial- and individual-level
      association between a potential surrogate and a true endpoint (Buyse et al.,
      2000, Biostatistics 1, 49-67). A drawback is that different settings have led to
      different measures at the individual level. Here, we use information theory to
      create a unified framework, leading to a definition of surrogacy with an
      intuitive interpretation, offering interpretational advantages, and applicable in
      a wide range of situations. Our method provides a better insight into the chances
      of finding a good surrogate endpoint in a given situation. We further show that
      some of the previous proposals follow as special cases of our method. We
      illustrate our methodology using data from a clinical study in psychiatry.

PMID- 17447944
TI  - Assessing the implications of publication bias for two popular estimates of
      between-study variance in meta-analysis.
AB  - Perhaps the greatest threat to the validity of a meta-analysis is the possibility
      of publication bias, where studies with interesting or statistically significant
      results are more likely to be published. This obviously impacts on inference
      concerning the treatment effect but also has implications for estimates of
      between-study variance. Two popular and established estimation methods are
      considered and formulae for assessing the implications of the bias are provided
      in terms of a general process for selecting studies. Meta-analysts, concerned
      that publication bias may be present, can use these as part of a sensitivity
      analysis to assess the robustness of their estimates of between-study variance
      using any selection process that is likely to be used in practice. The procedure
      is illustrated using a meta-analysis of clinical trials concerning the
      effectiveness of endoscopic sclerotherapy for preventing death in patients with
      cirrhosis and oesophagogastric varices.

PMID- 17447945
TI  - Nonparametric tests for two-group comparisons of dependent observations obtained
      at varying time points.
AB  - We propose new tests for two-group comparisons of repeated measures of a response
      where the repeated measures might be obtained at arbitrary time points that
      differ over individuals. The tests are almost U-statistics in that the kernel
      contains some unknown parameters that need to be estimated from the data. Our
      methods are designed for settings in which response means of one group are
      strictly greater than the response means of the other group. The tests do not
      make any assumptions regarding the distribution of the repeated measures except
      that one of the tests assumes that the repeated measures can be grouped into
      distinct periods of observations (e.g., around fixed follow-up time points) such
      that the covariance between scores only depends on the periods the observations
      belong to and that the covariance matrices are the same in the two groups. The
      tests are valid even if the probability that a response is observed depends on
      the level of response provided that the missing data mechanism is the same in
      both groups. Inference can conveniently be based on resampling. We provide
      asymptotic results for the test statistics. We investigate size and power of the
      tests and use them to assess differences in viral load decline for drug-resistant
      and drug-sensitive human immunodeficiency virus (HIV)-1 infected patients.

PMID- 17447946
TI  - Modeling of hormone secretion-generating mechanisms with splines: a pseudo
      likelihood approach.
AB  - A flexible and robust approach is proposed for the investigation of underlying
      hormone secretion-generating mechanisms. Characterizing hormone time series is a
      difficult task as most hormones are secreted in a pulsatile manner and pulses are
      often masked by slow decay. We model hormone concentration as a filtered counting
      process where the intensity function of the counting process is modeled
      nonparametrically using periodic splines. The intensity function and parameters
      are estimated using a combination of weighted least squares and pseudo-likelihood
      based on the first two moments. Our method uses concentration measurements
      directly, which avoids the difficult task of estimating pulse numbers and
      locations. Both simulations and applications suggest that our method performs
      well for estimating the intensity function of the pulse-generating counting
      processes.

PMID- 17447948
TI  - Test of marginal compatibility and smoothing methods for exchangeable binary data
      with unequal cluster sizes.
AB  - Exchangeable binary data are often collected in developmental toxicity and other
      studies, and a whole host of parametric distributions for fitting this kind of
      data have been proposed in the literature. While these distributions can be
      matched to have the same marginal probability and intra-cluster correlation, they
      can be quite different in terms of shape and higher-order quantities of interest
      such as the litter-level risk of having at least one malformed fetus. A sensible
      alternative is to fit a saturated model (Bowman and George, 1995, Journal of the
      American Statistical Association 90, 871-879) using the expectation-maximization
      (EM) algorithm proposed by Stefanescu and Turnbull (2003, Biometrics 59, 18-24).
      The assumption of compatibility of marginal distributions is often made to link
      up the distributions for different cluster sizes so that estimation can be based
      on the combined data. Stefanescu and Turnbull proposed a modified trend test to
      test this assumption. Their test, however, fails to take into account the
      variability of an estimated null expectation and as a result leads to inaccurate
      p-values. This drawback is rectified in this article. When the data are sparse,
      the probability function estimated using a saturated model can be very jagged and
      some kind of smoothing is needed. We extend the penalized likelihood method
      (Simonoff, 1983, Annals of Statistics 11, 208-218) to the present case of unequal
      cluster sizes and implement the method using an EM-type algorithm. In the
      presence of covariate, we propose a penalized kernel method that performs
      smoothing in both the covariate and response space. The proposed methods are
      illustrated using several data sets and the sampling and robustness properties of
      the resulting estimators are evaluated by simulations.

PMID- 17447947
TI  - Low-rank smoothing splines on complicated domains.
AB  - Smoothing over a domain with irregular boundaries or interior gaps and holes is
      addressed. Consider the problem of estimating mercury in sediment concentrations
      in the estuarine waters in New Hampshire. A modified version of low-rank thin
      plate splines (LTPS) is introduced where the geodesic distance is applied to
      evaluate dissimilarity of any two data observations: loosely speaking, distances
      between locations are not measured as the crow flies, but as the fish swims. The
      method is compared with competing smoothing techniques, LTPS, and finite element
      L-splines.

PMID- 17447949
TI  - A unified likelihood-based approach for estimating population size in continuous
      time capture-recapture experiments with frailty.
AB  - A unified likelihood-based approach is proposed to estimate population size for a
      continuous-time closed capture-recapture experiment with frailty. The frailty
      model allows the capture intensity to vary with individual heterogeneity, time,
      and behavioral response. The individual heterogeneity effect is modeled as being
      gamma distributed. The first-capture and recapture intensities are assumed to be
      in constant proportion but may otherwise vary arbitrarily through time. The
      approach is also extended to capture-recapture experiments with possible random
      removals. Simulation studies are conducted to examine the performance of the
      proposed estimators. By asymptotic efficiency comparison and simulation studies,
      the proposed estimators have been shown to be superior to their discrete-time
      model counterparts in genuine continuous-time capture-recapture experiments.

PMID- 17447950
TI  - Statistical analysis of unlabeled point sets: comparing molecules in
      chemoinformatics.
AB  - We consider Bayesian methodology for comparing two or more unlabeled point sets.
      Application of the technique to a set of steroid molecules illustrates its
      potential utility involving the comparison of molecules in chemoinformatics and
      bioinformatics. We initially match a pair of molecules, where one molecule is
      regarded as random and the other fixed. A type of mixture model is proposed for
      the point set coordinates, and the parameters of the distribution are a labeling
      matrix (indicating which pairs of points match) and a concentration parameter. An
      important property of the likelihood is that it is invariant under rotations and
      translations of the data. Bayesian inference for the parameters is carried out
      using Markov chain Monte Carlo simulation, and it is demonstrated that the
      procedure works well on the steroid data. The posterior distribution is difficult
      to simulate from, due to multiple local modes, and we also use additional data
      (partial charges on atoms) to help with this task. An approximation is considered
      for speeding up the simulation algorithm, and the approximating fast algorithm
      leads to essentially identical inference to that under the exact method for our
      data. Extensions to multiple molecule alignment are also introduced, and an
      algorithm is described which also works well on the steroid data set. After all
      the steroid molecules have been matched, exploratory data analysis is carried out
      to examine which molecules are similar. Also, further Bayesian inference for the
      multiple alignment problem is considered.

PMID- 17447951
TI  - An estimating function approach to inference for inhomogeneous Neyman-Scott
      processes.
AB  - This article is concerned with inference for a certain class of inhomogeneous
      Neyman-Scott point processes depending on spatial covariates. Regression
      parameter estimates obtained from a simple estimating function are shown to be
      asymptotically normal when the "mother" intensity for the Neyman-Scott process
      tends to infinity. Clustering parameter estimates are obtained using minimum
      contrast estimation based on the K-function. The approach is motivated and
      illustrated by applications to point pattern data from a tropical rain forest
      plot.

PMID- 17447952
TI  - Predicting patient survival from microarray data by accelerated failure time
      modeling using partial least squares and LASSO.
AB  - We consider the problem of predicting survival times of cancer patients from the
      gene expression profiles of their tumor samples via linear regression modeling of
      log-transformed failure times. The partial least squares (PLS) and least absolute
      shrinkage and selection operator (LASSO) methodologies are used for this purpose
      where we first modify the data to account for censoring. Three approaches of
      handling right censored data-reweighting, mean imputation, and multiple
      imputation-are considered. Their performances are examined in a detailed
      simulation study and compared with that of full data PLS and LASSO had there been
      no censoring. A major objective of this article is to investigate the
      performances of PLS and LASSO in the context of microarray data where the number
      of covariates is very large and there are extremely few samples. We demonstrate
      that LASSO outperforms PLS in terms of prediction error when the list of
      covariates includes a moderate to large percentage of useless or noise variables;
      otherwise, PLS may outperform LASSO. For a moderate sample size (100 with 10,000
      covariates), LASSO performed better than a no covariate model (or noise-based
      prediction). The mean imputation method appears to best track the performance of
      the full data PLS or LASSO. The mean imputation scheme is used on an existing
      data set on lung cancer. This reanalysis using the mean imputed PLS and LASSO
      identifies a number of genes that were known to be related to cancer or tumor
      activities from previous studies.

PMID- 17447953
TI  - Robustness of prevalence estimates derived from misclassified data from
      administrative databases.
AB  - Because primary data collection can be expensive, researchers are increasingly
      using information collected in medical administrative databases for scientific
      purposes. This information, however, is typically collected for reasons other
      than research, and many such databases have been shown to contain substantial
      proportions of misclassification errors. For example, many administrative
      databases contain fields for patient diagnostic codes, but these are often
      missing or inaccurate, in part because physician reimbursement schemes depend on
      medical acts performed rather than any diagnosis. Errors in ascertaining which
      individuals have a given disease bias not only prevalence estimates, but also
      estimates of associations between the disease and other variables, such as
      medication use. We attempt to estimate the prevalence of osteoarthritis (OA)
      among elderly Quebeckers using a government administrative database. We compare a
      naive estimate relying solely on the physician diagnoses of OA listed in the
      database to estimates from several different Bayesian latent class models which
      adjust for misclassified physician diagnostic codes via use of other available
      diagnostic clues. We find that the prevalence estimates vary widely, depending on
      the model used and assumptions made. We conclude that any inferences from these
      databases need to be interpreted with great caution, until further work
      estimating the reliability of database items is carried out.

PMID- 17447954
TI  - Semiparametric bayesian inference for multilevel repeated measurement data.
AB  - We discuss inference for data with repeated measurements at multiple levels. The
      motivating example is data with blood counts from cancer patients undergoing
      multiple cycles of chemotherapy, with days nested within cycles. Some inference
      questions relate to repeated measurements over days within cycle, while other
      questions are concerned with the dependence across cycles. When the desired
      inference relates to both levels of repetition, it becomes important to reflect
      the data structure in the model. We develop a semiparametric Bayesian modeling
      approach, restricting attention to two levels of repeated measurements. For the
      top-level longitudinal sampling model we use random effects to introduce the
      desired dependence across repeated measurements. We use a nonparametric prior for
      the random effects distribution. Inference about dependence across second-level
      repetition is implemented by the clustering implied in the nonparametric random
      effects model. Practical use of the model requires that the posterior
      distribution on the latent random effects be reasonably precise.

PMID- 17447955
TI  - A note on testing separability in spatial-temporal marked point processes.
AB  - In environmental risk analysis, it is common to assume the stochastic
      independence (or separability) between the marks associated with the random
      events of a spatial-temporal point process. Schoenberg (2004, Biometrics 60, 471
      481) proposed several test statistics for this hypothesis and used simulated data
      to evaluate their performance. He found that a Cramer-von Mises-type test is
      powerful to detect gradual departures from separability although it is not
      uniformly powerful over a large class of alternative models. We present a
      semiparametric approach to model alternative hypotheses to separability and
      derive a score test statistic. We show that there is a relationship between this
      score test and some of the test statistics proposed by Schoenberg. Specifically,
      all are different versions of weighted Cramer-von Mises-type statistics. This
      gives some insight into the reasons for the similarities and differences between
      the test statistics' performance. We also point out some difficulties in
      controlling the type I error probability in Schoenberg's residual test.

PMID- 17447957
TI  - Drawbacks to noninteger scoring for ordered categorical data.
AB  - A proposal to improve trend tests by using noninteger scores is examined. It is
      concluded that despite improved power such tests are usually inferior to the
      simpler integer scored approach.

PMID- 17447970
TI  - Mammary and extramammary Paget's disease.
AB  - Paget's disease is an intra-epidermal adenocarcinoma seen over the nipple/areola
      (mammary Paget's disease) or in extramammary body zones, such as the anogenital
      and perineal skin and the axilla. Mammary and extramammary Paget's disease share
      many common clinicopathological features but also show several differences,
      namely, with regard to pathogenesis and association with underlying malignancies.
      Indeed, mammary Paget's disease is as a rule associated with an underlying breast
      carcinoma whereas association of extramammary Paget's disease with underlying
      (skin or visceral) malignancies occurs much less frequently. We review here the
      main clinicopathological and therapeutic features of mammary and extramammary
      Paget's disease.

PMID- 17447971
TI  - A confusing world: what to call histology of three-dimensional tumour margins?
AB  - Complete three-dimensional histology of excised skin tumour margins has a long
      tradition and, unfortunately, a multitude of names as well. Mohs, who introduced
      it, called it 'microscopically controlled surgery'. Others have described it as
      'micrographic surgery', 'Mohs' micrographic surgery', or simply 'Mohs' surgery'.
      Semantic confusion became truly rampant when variant forms, each useful in its
      own way for detecting subclinical outgrowths of malignant skin tumours, were
      later introduced under such names as histographic surgery, systematic histologic
      control of the tumour bed, histological control of excised tissue margins, the
      square procedure, the perimeter technique, etc. All of these methods are
      basically identical in concept. All involve complete, three-dimensional
      histological visualization and evaluation of excision margins. Their common goal
      is to detect unseen tumour outgrowths. For greater clarity, the authors of this
      paper recommend general adoption of '3D histology' as a collective designation
      for all the above methods. As an added advantage, 3D histology can also be used
      in other medical disciplines to confirm true R0 resection of, for example, breast
      cancer or intestinal cancer.

PMID- 17447972
TI  - An open-label efficacy pilot study with pimecrolimus cream 1% in adults with
      facial seborrhoeic dermatitis infected with HIV.
AB  - BACKGROUND: Seborrhoeic dermatitis (SD) is a common dermatosis in human
      immunodeficiency virus (HIV)-positive patients, many of whom do not respond
      satisfactorily to conventional topical treatments such as corticosteroids and
      antifungals. OBJECTIVE: A pilot study to investigate the efficacy and
      tolerability of pimecrolimus cream 1% in HIV-positive patients with facial SD.
      METHODS: In a single-centre study, 21 HIV-infected patients with mild to severe
      SD were treated twice daily with pimecrolimus cream 1% for 14 days. Thereafter,
      treatment was discontinued and patients followed up for 5 weeks. Skin involvement
      at baseline and on days 7, 14, 21, 35 and 49 was assessed using a four-point
      clinical score and digital photography. MAIN OUTCOME MEASURES: Efficacy and
      safety of pimecrolimus cream 1% treatment and incidence of relapse in the follow
      up phase. Results Marked improvement was seen in clinical parameters at day 7,
      with >or= 90% patients clear of symptoms at day 14. Relapse was observed at day
      35 but signs were milder than at baseline. All patients responded to therapy,
      despite their immunological status. Pimecrolimus did not alter CD4(+) and CD8(+)
      T-cell counts or viral load during the treatment period. CONCLUSION: Pimecrolimus
      cream represents a new, effective therapeutic option for facial SD in HIV
      patients.

PMID- 17447973
TI  - The familial risk of acne vulgaris in Chinese Hans - a case-control study.
AB  - BACKGROUND: Acne is a chronic inflammatory disease of the pilosebaceous
      follicles. Recent studies bring us increasing evidences that hereditary factors
      play an important but indirect role in acne. OBJECTIVE: To investigate the
      possible role of genetic factors in the pathogenesis of acne vulgaris in Chinese
      Han ethnic group. PATIENTS AND METHODS: Volunteers of 975 acne cases and 580
      controls were included, contributing 3009 and 1825 first-degree relatives,
      respectively. One thousand and eighty-five first-degree relatives of acne cases
      were affected with facial acne. This compared with 223 first-degree relatives of
      non-acne controls. The odds ratio was used to estimate the relative risk for acne
      vulgaris associated with having an affected first-degree relative. RESULTS: The
      risk of acne vulgaris occurring in a relative of a patient with acne vulgaris was
      significantly greater than for the relative of an unaffected individual (odds
      ratio 4.05, 95% confidence interval (CI): 3.45-4.76, P<0.001). CONCLUSION: Our
      study suggests that familial factors are important in determining individual
      susceptibility to acne vulgaris.

PMID- 17447974
TI  - Cyclosporin in the treatment of patients with atopic eczema - a systematic review
      and meta-analysis.
AB  - OBJECTIVE: To systematically assess the effectiveness of systemic cyclosporin in
      patients with severe atopic eczema. STUDY DESIGN: Systematic review and meta
      analysis of controlled and uncontrolled trials. Electronic (MEDLINE, Cochrane
      databases) and hand search of published work. Independent standardized assessment
      of eligibility and data abstraction by two reviewers. METHODS: For the
      qualitative review data on study design, study population, methodology, results,
      tolerability and methodological quality was independently extracted by two
      reviewers. Qualitatively homogeneous studies were pooled using a random-effects
      model. The mean relative change in objective disease severity was chosen as the
      main outcome measure for the quantitative analysis. Publication bias was explored
      by regressing treatment effect on sample size. Sensitivity analysis included meta
      regression of study-specific covariates (inclusion of children, study type,
      concomitant topical therapy, study quality). RESULTS: Fifteen studies including
      602 patients met the eligibility criteria. In all studies analysed, cyclosporin
      consistently decreased the severity of atopic eczema. Twelve studies appeared
      homogeneous enough to be pooled. After 2 weeks of treatment we found a dose
      related response with a pooled mean decrease in disease severity of 22% (95%-CI 8
      36%) under low-dose cyclosporin ( 3 mg/kg) and 40% (95%-CI 29-51%) at dosages
      >or=4 mg/kg. After 6-8 weeks the relative effectiveness was 55% (95%-CI 48-62%).
      CONCLUSIONS: Due to evidence of publication bias the quantitative results need to
      be interpreted with caution. Effectiveness of cyclosporin is similar in adults
      and children, but tolerability might be better in children. As data to adequately
      evaluate the long-term effectiveness and safety of cyclosporin in patients with
      atopic eczema are unavailable, long-term registries are encouraged.

PMID- 17447975
TI  - Sensitive skin: psychological effects and seasonal changes.
AB  - INTRODUCTION: Sensitive skin is a frequent disorder, but its effects and its
      variability are unknown. OBJECTIVES: To investigate the effects of sensitive skin
      first on quality of life and the psyche, and secondly, on seasonal changes.
      METHODS: The French Opinion Poll Institute (IPSOS) conducted two opinion polls in
      March and July 2004. Samples included, respectively, 1006 and 1001 individuals,
      from a representative national sample of the French population aged 15 years or
      older. The polling subjects were interviewed by phone and selected by the quota
      method (gender, age, occupation of household head, type of geographical area and
      region). Questions about their perception of their sensitive skin and about
      potential aggravating factors were asked. Quality of life was assessed using the
      SF-12 questionnaire and depressive symptoms using the Hospital Anxiety and
      Depression (HAD) rating scale. RESULTS: The characteristics of the two samples
      were strictly similar. Persons with sensitive skin and very sensitive skin were
      more numerous in summer than in winter. In both surveys, the degree of
      sensitivity was significantly higher in the female population. Quality of life
      was worse in people with sensitive or very sensitive skin, above all in its
      psychological component - the more sensitive the skin, the more the quality of
      life deteriorated. There was no significant relationship between depressive
      symptoms and skin sensitivity in the 'very sensitive' or 'sensitive' groups.
      CONCLUSION: Our study was the first to show seasonal changes in skin reactivity
      and to study the psychological impacts of sensitive skin.

PMID- 17447976
TI  - S-nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair.
AB  - BACKGROUND: Nitric oxide (NO) plays a key role in wound repair and S
      nitrosothiols like S-nitrosoglutathione (GSNO) are well known NO donors. METHODS:
      Animals were separated in two groups and submitted to excisional wounds on the
      dorsal surface at the first day. GSNO (100 microm)-containing hydrogels were
      topically applied on the wound bed in the GSNO group, daily, during the first 4
      days. Control group was topically treated with hydrogel without GSNO for the same
      period. Wound contraction and re-epithelialization were measured. Animals were
      sacrificed 21 days after wounding. Samples of lesion and normal tissue were
      formalin-fixed, paraffin embedded for histological analysis. RESULTS: Wound
      contraction, measured 14 and 21 days after wounding, was greater in the GSNO
      group than in the control group (P<0.05 for both). The re-epithelialized wound
      area, measured 14 days after wounding, was higher in the GSNO group than in the
      control group (P<0.05). A higher amount of inflammatory cells was observed in
      superficial and deep areas of the granulation tissue of the control group
      compared to the GSNO group. Twenty-one days after wounding, thin red-yellow
      collagen fibers arranged perpendicularly to the surface were found in the
      granulation tissue of the control group, whereas in the GSNO-treated group
      collagen fibers were thicker and arranged parallel to the surface. Increased
      number of mast cells was observed in the GSNO group compared with that in the
      control group. Vascularization and myofibroblast distribution were similar in
      both groups. CONCLUSION: Topical application of GSNO-containing hydrogel during
      the early phases of rat cutaneous wound repair accelerates wound closure and re
      epithelialization and affects granulation tissue organization.

PMID- 17447977
TI  - Comparison of systemic PUVA and NB-UVB in the treatment of vitiligo: an open
      prospective study.
AB  - BACKGROUND: Vitiligo is a common pigmentary disorder with great cosmetic and
      psychological morbidity. No treatment available is a definitive cure. Systemic
      psoralen and ultraviolet A (PUVA) has been the mainstay of treatment. Narrow-band
      ultraviolet B (NB-UVB) has been recently introduced. Although retrospective
      comparative study of systemic PUVA and NB-UVB has been published from our centre,
      no prospective study has been reported to date. AIMS: To investigate the position
      of NB-UVB vis-a-vis PUVA in terms of efficacy, time to repigment and adverse
      effects and to help decide if one therapy has an advantage over another in the
      treatment of vitiligo. SUBJECTS AND METHODS: It was a randomized, open,
      prospective study of 50 patients divided equally in TMP PUVA and NB-UVB groups.
      The study period was from January 2004 to June 2005. RESULTS: The mean degree of
      repigmentation attained in the NB-UVB group was 52.24% over a mean treatment
      period of 6.3 months, whereas in the PUVA group it was 44.7% in a mean period of
      5.6 months (P=0.144). After excluding the results of therapy-resistant sites,
      that is, hands and feet, the mean degree of repigmentation in the NB-UVB group
      was 67.57%, whereas in the PUVA group it was 54.2% (P=0.007). CONCLUSIONS: NB-UVB
      performed better in comparison to TMP PUVA in terms of mean total repigmentation
      when traditionally considered therapy-resistant sites were excluded.

PMID- 17447978
TI  - Prevalence of childhood acne, ephelides, warts, atopic dermatitis, psoriasis,
      alopecia areata and keloid in Kaohsiung County, Taiwan: a community-based
      clinical survey.
AB  - BACKGROUND: Epidemiological study on childhood dermatoses performed by direct
      inspection of dermatologists is limited. OBJECTIVE: To investigate the prevalence
      of selective childhood dermatoses in Taiwan. METHODS: In a cross-sectional study
      carried out in June 2004, 4067 of 7851 children aged between 6 and 11 years
      living in the Kaohsiung County in south Taiwan were clinically surveyed and
      examined by two board-certified dermatologists (response rate 52%), regarding the
      point prevalence of acne, ephelides, warts, atopic dermatitis (AD), psoriasis,
      alopecia areata (AA) and keloid. RESULTS: Acne vulgaris was found in girls and
      boys from the age of 6 and 7, respectively, with comedones being the earliest
      presentation. Ephelides were not infrequently observed in our children
      (prevalence rate 8.4%, 95% confidence interval, CI 7.9-9.3%). The prevalence of
      warts on hands was 2.4% (95% CI 1.9-2.9%). The prevalence of AD was 1.7% (95% CI
      1.3-2.1%), without gender difference. There were only four cases of AA but no
      psoriasis was found. Keloid was identified in 13 boys and 10 girls, accounting
      for 0.6% (95% CI 0.598-0.602%) of the children. CONCLUSION: Acne vulgaris is as
      common in Taiwan as in Western countries. Ephelides are not uncommon in our
      population with the main skin types III-IV. A clustered distribution of the wart
      infection was noted. The low prevalence of AD in Taiwan seems unaltered over the
      past decade. AA and psoriasis are rare in our series. Most keloids in our
      children are caused by BCG vaccination.

PMID- 17447979
TI  - Effects of polyphenols on skin damage due to ultraviolet A rays: an experimental
      study on rats.
AB  - BACKGROUND: Ultraviolet (UV) radiation causes many acute and chronic conditions
      such as oedema of the skin, sunburn, immunosuppression, photo-ageing and skin
      cancer. The use of antioxidants has become of paramount importance in prevention
      of the damage caused by ultraviolet radiation. Epigallocatechin-3-gallate (EGCG),
      one of the main components of green tea, has been reported to have anti
      inflammatory, antioxidant and anticarcinogenic properties. AIM: The aim of this
      experimental study was to investigate to what extent EGCG prevented acute skin
      damage caused by UVA. MATERIAL AND METHOD: The sample contained 2% EGCG, which
      was prepared in hydrophilic ointment (USP XXIV) as the vehicle. Twenty-four 12
      week-old Wistar albino rats are included in the study and divided into four
      groups, each containing six rats. Group I was formed to be the control group,
      which was not applied any topical medication or exposed to UV radiation. Group II
      was formed to observe acute effects of UVA on the skin, Group III was formed to
      observe effectiveness of topical EGCG on the skin applied 30 min after exposure
      to UVA, and Group IV was formed to observe topical EGCG applied 30 min before
      exposure to UVA. All groups were examined for sunburn cells, leucocyte
      infiltration, dermo-epidermal activity, collagen changes and elastic fibre
      pathologies on 24 and 72 h. Statistical analysis was performed using spss 11.5,
      and chi-squared test was used for the evaluation of parameters. RESULTS: Group IV
      showed a statistically significant decrease in sunburn cells and dermo-epidermal
      activation compared with Group II. Group II showed significant increase in all
      parameters compared with Group I, showing the effects of UV exposure alone, and
      no difference was detected in Group II and III. CONCLUSION: These results show a
      protective effect of EGCG when applied topically before UVA exposure. No benefit
      was detected when EGCG was applied after UV exposure.

PMID- 17447980
TI  - Smoothing the mosaic subclinical melanoderma by calcipotriol.
AB  - BACKGROUND: The observation of photo-exposed skin under ultraviolet light reveals
      a mosaic pattern of varying intensity in epidermal melanization. Several patterns
      of mosaic subclinical melanoderma (MSM) have been described using a specially
      designed CCD camera and the ultraviolet light-enhanced visualization (ULEV)
      method. Vitamin D(3) and its analogues influence the biology of keratinocytes and
      melanocytes. OBJECTIVE: To assess the effect of calcipotriol on MSM. METHODS:
      This randomized split-face study was conducted in 27 men to compare the effect of
      once daily applications of 5% calcipotriol cream or a moisturizing cream on the
      heterogeneity of facial MSM. Computerized image analysis of video images was used
      at 1-month intervals before and during a 2-month treatment, as well as during a 3
      month follow-up. RESULTS: At both sites, the average melanin content of the
      epidermis showed no significant change over time. However, the mottled appearance
      was smoothened at the calcipotriol site, whereas it was increased at the site
      receiving the moisturizer. CONCLUSION: The decreased heterogeneity in MSM after
      calcipotriol applications suggests a control of the epidermal melanocyte unit by
      the vitamin D(3) derivative.

PMID- 17447981
TI  - Psychosocial well-being of patients with skin diseases in general practice.
AB  - BACKGROUND: Skin diseases are a substantial part of the problems dealt with by
      general practitioners. Although the psychosocial consequences of skin diseases in
      secondary care has been extensively studied, little is known about the
      psychosocial well-being of patients with skin diseases in primary care.
      OBJECTIVE: To investigate the psychosocial well-being of patients with skin
      diseases in primary care. PATIENTS/METHODS: Questionnaires about the psychosocial
      consequences of skin diseases were sent to patients with a skin disease who were
      registered within a research network (continuous morbidity registration) of
      general practices that continuously have recorded morbidity data since 1971.
      Questionnaires completed by 532 patients were eventually suitable for analyses.
      RESULTS: Compared with the general population, patients with skin diseases
      reported significantly lower scores for psychosocial well-being. Furthermore, a
      lower psychosocial wellbeing was significantly related with higher levels of
      disease-severity, lower disease-related quality of life, longer disease duration,
      more comorbidity and more physical symptoms of itch, pain and fatigue. After
      demographic variables and comorbidity were controlled for, sequential regression
      analyses showed that disease duration, disease severity and physical symptoms
      (itch, pain and fatigue) were significant predictors of psychosocial well-being.
      CONCLUSION: The psychosocial well-being of patients with skin diseases in primary
      care is lower than that of the general population. Special attention has to be
      directed to those patients with lowered psychosocial well-being who might be at
      risk of developing severe psychosocial impairments such as clinical depression.

PMID- 17447982
TI  - Comparison of metallothionein-overexpression with sentinel lymph node biopsy as
      prognostic factors in melanoma.
AB  - BACKGROUND: Metallothioneins (MT) are ubiquitous, intracellular small proteins
      with high affinity for heavy metal ions. Immunohistochemical MT overexpression in
      paraffin-embedded tissues of patients with primary melanoma is associated with
      poor prognosis. While sentinel lymph node (SLN) biopsy is an established surgical
      technique for high-risk melanoma patients with predictive value for progression,
      the benefit of this procedure for the individual patient's overall survival
      remains unclear. AIM AND METHODS: We examined the role of MT overexpression in
      comparison with SLN biopsy in melanoma patients as a prognostic marker for
      progression and survival. One hundred and fifty-eight (158) patients underwent
      SLN biopsy due to high-risk melanoma. Primary melanoma specimens were
      investigated by using a monoclonal antibody against MT on routinely fixed,
      paraffin-embedded tissues. The patients were followed up (median 37 months); the
      data of disease free survival and overall survival were calculated with a broad
      panel of statistical analyses. RESULTS: Twenty-eight (18%) out of 158 recruited
      melanoma patients developed metastases, 17 (11%) patients died due to widespread
      disease. Kaplan-Meier curves gave significant disadvantages for the MT-positive
      as well as the SLN-positive group for progression and survival. In the Fisher's
      exact test and Pearson's chi(2)-test MT overexpression was highly significant for
      progression, whereas SLN biopsy failed significance. In univariate as well as
      multivariate Cox regression analysis MT overexpression proved an excellent marker
      for progression (P=0.007 and P=0.009), although the P-values for survival were
      not significant. In contrast, while in the univariate analysis SLN biopsy did not
      show significant results for progression it did for survival, and in the
      multivariate analysis reached a P-value < 0.05 for both measured endpoints.
      CONCLUSION: Results corroborate the validity of MT overexpression in primary
      melanoma as a useful prognostic marker in melanoma patients. Accuracy is
      comparable and to some degree supplementary to the results of SLN biopsy.

PMID- 17447983
TI  - A leg ulcer as manifestation of metastatic squamous cell vaginal carcinoma.
AB  - Cutaneous metastasis of vaginal carcinoma is extremely rare. So far, the total
      number of reported skin metastasis of vaginal carcinoma is only one. We present
      another case with an unusual manifestation of vagina carcinoma metastasis: skin
      metastasis presenting as a leg ulcer on the lower leg.

PMID- 17447984
TI  - Vitiliginous lesions after photosensitive dermatitis due to flutamide.

PMID- 17447985
TI  - Crusted scabies of the vulva.

PMID- 17447986
TI  - Interstitial granulomatous dermatitis associated with autoimmune hepatitis.

PMID- 17447987
TI  - A case of papular mycosis fungoides: new clinical variant of early mycosis
      fungoides.

PMID- 17447988
TI  - Development of varicella during adalimumab therapy.

PMID- 17447989
TI  - Proliferating pilomatricoma mimicking pyogenic granuloma.

PMID- 17447990
TI  - Naevus en cocarde (hoop-loop naevus).

PMID- 17447991
TI  - Attenuated ubiquitination of molluscum bodies in agminated mollusca contagiosa
      associated with malignant lymphoma.

PMID- 17447992
TI  - Photochemotherapy and methotrexate used to treat generalized cutaneous
      scleroderma.

PMID- 17447993
TI  - A case of generalized granuloma annulare with myelodysplastic syndrome:
      successful treatment with systemic isotretinoin and topical pimecrolimus 1% cream
      combination.

PMID- 17447994
TI  - Chronic cutaneous leishmaniasis in an immunocompetent patient: response to
      miltefosine.

PMID- 17447995
TI  - Pemphigus herpetiformis associated with prostate cancer.

PMID- 17447996
TI  - Cutaneous pemphigus vulgaris.

PMID- 17447997
TI  - Onychocryptosis as consequence of effective treatment of dermatophytic
      onychomycosis.

PMID- 17447999
TI  - Pustular allergic contact dermatitis from topical minoxidil 5%.

PMID- 17448000
TI  - Contralaterally spreading type III nevus of Ota in a white person.

PMID- 17447998
TI  - The specific dermoscopical criteria of Bowen's disease.

PMID- 17448001
TI  - Epidemiology of onychomycosis in central Poland.

PMID- 17448002
TI  - A case of pigmented fungiform lingual papillae in an Indian woman.

PMID- 17448003
TI  - A case of keratitis ichthyosis deafness (KID) syndrome associated with Dandy
      Walker.

PMID- 17448004
TI  - Rapid healing of long-lasting sickle cell leg ulcer treated with allogeneic
      keratinocytes.

PMID- 17448005
TI  - Nodular cystic fat necrosis in Heerfordt's syndrome.

PMID- 17448006
TI  - Paronychia in an HIV-infected patient under nelfinavir therapy.

PMID- 17448007
TI  - Prurigo nodularis in healed herpes zoster scar: an isotopic response.

PMID- 17448008
TI  - Ambilateral reactivation of herpes zoster V2 following cataract operation of both
      eyes.

PMID- 17448009
TI  - Nevus spilus maculosus vs. partial unilateral lentiginosis.

PMID- 17448010
TI  - Is black henna responsible for asthma and cross reactivity with latex?

PMID- 17448011
TI  - CHILD syndrome: clinical picture and diagnostic procedures.

PMID- 17448012
TI  - Overlap of acute generalized exanthematous pustulosis and toxic epidermal
      necrolysis: response to antitumour necrosis factor-alpha antibody infliximab:
      report of three cases.

PMID- 17448013
TI  - Dercum's disease (adiposis dolorosa): a report of improvement with infliximab and
      methotrexate.

PMID- 17448014
TI  - Lichen planus: an unusual cause of oesophageal stricture.

PMID- 17448015
TI  - Laboratory handling and histology reporting of breast specimens from patients who
      have received neoadjuvant chemotherapy.
AB  - Neoadjuvant chemotherapy is increasingly being offered to patients with invasive
      breast carcinoma but surgical excision specimens following such therapy may be
      difficult to interpret in the pathology laboratory, both macroscopically and
      histologically. We provide here some guidelines for handling such postneoadjuvant
      chemotherapy samples and describe the histopathological features which may be
      encountered in both the breast and lymph nodes received. We also present a brief
      review of the literature and suggest a simple method for quantifying the degree
      of response to neoadjuvant chemotherapy in both the primary breast carcinoma and
      the lymph nodes.

PMID- 17448016
TI  - Aberrant expression of TopBP1 in breast cancer.
AB  - AIMS: The TopBP1 protein includes eight BRCT domains (originally identified in
      BRCA1) and has homology with BRCA1 over the carboxyl terminal half of the
      protein. The aim of this study was to determine whether TopBP1 is aberrantly
      expressed in breast cancer. METHODS AND RESULTS: Sixty-one breast carcinomas from
      an unselected consecutive patient cohort were studied along with 12 samples of
      breast tissue from cosmetic breast reduction surgery; these were analysed
      immunohistochemically for TopBP1 expression using a rabbit polyclonal antibody.
      This antibody was validated in immunoprecipitation and immunofluorescence
      experiments. Immunohistochemical analysis demonstrated that TopBP1 was expressed
      almost exclusively in the nuclei of the normal breast epithelium. However, in a
      significant number of breast carcinomas TopBP1 was aberrantly expressed, as it
      was detected in the cytoplasm and nucleus of some tumours and exclusively in the
      cytoplasm of others. In two out of 61 carcinomas investigated, no TopBP1
      expression was detected. CONCLUSIONS: For the first time this report demonstrates
      aberrant expression of the TopBP1 protein in breast carcinoma. We propose TOPBP1
      as a breast cancer susceptibility gene.

PMID- 17448017
TI  - Expression of oestrogen receptor-beta in apocrine carcinomas of the breast.
AB  - AIMS: Apocrine carcinoma of the breast seldom expresses oestrogen receptors (ER)
      or progesterone receptors (PR), but frequently expresses androgen receptors (AR).
      Because of this unusual hormone receptor status, it has been suggested that
      oestrogens have a less important role in the pathogenesis of apocrine carcinoma.
      The ER status of apocrine carcinoma has been studied for one kind of ER, the
      classic receptor now named ER-alpha; however, the status of ER-beta, a secondary
      oestrogen receptor, has not been examined systematically in apocrine carcinoma.
      The aim was to study ER-beta status in apocrine carcinoma. METHODS AND RESULTS:
      The expression of ER-beta was examined immunohistochemically in 48 apocrine
      carcinomas and compared with clinicopathological factors and ER-alpha, PR and AR
      status. ER-beta positivity was observed in 35 cases (73%), regardless of any
      clinicopathological factors or the status of other receptors. The results of ER
      beta mRNA analysis supported the immunohistochemical results. CONCLUSIONS: The
      significance of oestrogens in apocrine carcinoma should not be dismissed at
      present when the role of ER-beta remains to be determined. Studying the action of
      oestrogen or antioestrogen in apocrine carcinoma may reveal a role for ER-beta
      independent of ER-alpha and raise the potential of hormonal therapy for these
      tumours.

PMID- 17448019
TI  - Mammary and extramammary Paget's disease: an immunohistochemical study of 83
      cases.
AB  - AIM: Mammary Paget's disease (MPD) and extramammary Paget's disease (EMPD) are
      rare neoplasms. The aim of this study was, by the use of immunohistochemistry, to
      derive further information about the cell(s) of origin, find a diagnostically
      useful immunohistochemical panel and investigate candidates for possible targeted
      therapy. MATERIAL AND RESULTS: Sixty MPD and 23 EMPD cases were studied using
      antibodies to cytokeratin (CK) 34betaE12, CK8/18, CK7, CK5/6, CK20, gross cyctic
      disease fluid protein (GCDFP)-15, MUC1-8, epidermal growth factor receptor (EGFR)
      (HER1), HER3 and HER4. In all MPD cases CK7 and MUC1 were positive. CK8/18 was
      positive in 59/60 cases. GCDFP-15, MUC2, MUC3, MUC4, MUC7, MUC8 were positive in
      29/60, 3/60, 35/47, 4/40, 3/43 and 2/45 cases, respectively. In all EMPD cases
      CK8/18 and CK7 were positive. MUC1, GCDFP-15, MUC5AC, MUC3, MUC8 and CK20 were
      positive in 22/23, 19/23, 8/19, 3/19, 1/19 and 3/23 cases, respectively. With the
      remaining antibodies no immunoreactivity was observed. CONCLUSION: MUC1 and low
      molecular-weight CKs in conjunction with immunonegativity for high-molecular
      weight CKs are the most diagnostically useful markers. MPD is caused by the
      epidermotropic spread of underlying tumour cells, whereas EMPD probably arises
      from intraepithelial cells of sweat gland origin. Targeted therapy with
      antibodies against EGFR (HER1), HER3 or HER4 is unlikely to prove of clinical
      value.

PMID- 17448018
TI  - Breast carcinoma with basal differentiation: a proposal for pathology definition
      based on basal cytokeratin expression.
AB  - AIM: To assess the expression and coexpression of a range of different biomarkers
      that have been used to define breast carcinomas with a basal phenotype (BP) and
      their relationship with prognosis in an attempt to refine the definition of BP
      and to evaluate the reliability of using a single biomarker to identify these
      tumours. METHODS AND RESULTS: The expression pattern of basal cytokeratins (CK5/6
      and CK14), oestrogen, progesterone and androgen receptors, epidermal growth
      factor receptor, HER2, BRCA1, P-cadherin and myoepithelial markers (smooth muscle
      actin and p63) were studied in a well-characterized series of invasive breast
      carcinoma (1872 cases) with long-term follow-up using immunohistochemistry and
      tissue microarray. Although the additional markers were associated with basal CK
      expression, they did not serve to improve recognition of cases with differing
      outcome when compared with basal CKs alone and, if used to define cases, reduced
      considerably the proportion of cases allocated to this poor prognostic type of
      breast cancer. CONCLUSION: BP can be defined based on the expression of basal CKs
      regardless of the expression of other markers.

PMID- 17448020
TI  - Expression of platelet-derived growth factor receptor in low-grade endometrial
      stromal sarcomas in the absence of activating mutations.
AB  - AIMS: To investigate platelet-derived growth factor receptor (PDGFR)alpha and
      PDGFRbeta expression and a mutational analysis of PDGFRalpha (exons 11, 12, 17
      and 18) and PDGFRbeta (exon 12) genes in endometrial stromal sarcomas (ESS).
      Gastrointestinal stromal tumours (GISTs), which have somatic mutations of the
      transmembrane tyrosine kinase receptor, respond to tyrosine kinase inhibitors,
      which act through an inhibitory effect on class 3 receptor tyrosine kinase
      members such as PDGFRalpha, PDGFRbeta and c-kit. METHODS AND RESULTS: The
      immunohistochemical expression of PDGFRalpha and PDGFRbeta was investigated in 37
      archival c-kit- ESS. Staining was scored as negative (0-10% positive tumour
      cells) and positive (weakly positive 11-50% positive cells; strongly positive >
      50% positive cells). PDGFRalpha was expressed in 24/37 ESS [65%; strongly by
      19/37 (51.5%) and weakly by 5/37 ESS (13.5%)]. ESS tumour cells were negative for
      PDGFRbeta, but endothelial cells stained positive. A mutational analysis of
      PDGFRalpha (exons 11, 12, 17 and 18) and PDGFRbeta (exon 12) genes on frozen
      metastatic ESS from three patients detected no mutations leading to amino acid
      changes in the mature protein. CONCLUSIONS: Patients with PDGFRalpha+ ESS may
      benefit from treatment with tyrosine kinase inhibitors by blocking autocrine and
      paracrine stimulation loops, blocking neovascularization and enhancing the
      effects of chemotherapy.

PMID- 17448021
TI  - Prognostic significance of the wnt signalling pathway molecules APC, beta-catenin
      and E-cadherin in colorectal cancer: a tissue microarray-based analysis.
AB  - AIMS: To investigate dysregulation of the wnt signalling pathway by assessing
      beta-catenin expression/increasing expression and loss of cytoplasmic adenomatous
      polyposis coli (APC) and membranous E-cadherin in colorectal cancer (CRC) and
      determining the prognostic significance of these variables. METHODS AND RESULTS:
      Unselected, non-consecutive CRC resections (n = 1420) were subdivided into three
      groups: mismatch repair (MMR)-proficient, MLH1- and presumed hereditary non
      polyposis colonic cancer (HNPCC). Immunohistochemical analysis of beta-catenin
      expression (0% versus > 0%) and increasing expression (increasing percentage
      positivity) and loss of APC and E-cadherin was performed using the tissue
      microarray technique. In MMR-proficient CRC, increased nuclear beta-catenin
      expression and loss of membranous E-cadherin were independently associated with
      higher N stage (P = 0.03 and < 0.0001), vascular invasion (P < 0.01 and < 0.001)
      and worse survival (P < 0.01 and < 0.001). Additionally, there was an association
      between loss of membranous E-cadherin and higher T stage (P = 0.03). In MLH1-
      CRC, loss of membranous E-cadherin was associated with higher N stage (P = 0.05)
      and worse survival (P = 0.03). In presumed HNPCC CRC nuclear beta-catenin and
      membranous E-cadherin were not associated with tumour progression or worse
      survival. In all CRC subsets loss of cytoplasmic APC was not associated with
      clinicopathological features. CONCLUSIONS: Increasing nuclear beta-catenin
      expression and loss of membranous E-cadherin are independent, adverse prognostic
      factors in MMR-proficient and MLH1- CRC.

PMID- 17448022
TI  - Coeliac disease: a histological follow-up study.
AB  - AIMS: To assess the histological response to a gluten-free diet (GFD) in a series
      of coeliac patients in clinical remission, of different ages and with varying
      degrees of mucosal damage at diagnosis. METHODS AND RESULTS: Biopsy samples from
      249 coeliac patients (F 165, M 84) were analysed basally and after clinical and
      biochemical remission following a GFD. All patients showed an improvement in
      mucosal findings after starting a GFD, but complete histological normalization
      was observed in 74.1% of paediatric cases (diagnosed before 14 years of age) and
      in only 17.5% of adults. Statistical analysis showed that sex, the clinical
      picture at diagnosis and the length of time between biopsy at the time of
      diagnosis and on a GFD were not related to histological normalization. In
      contrast, the age at diagnosis was statistically significantly related to it (P <
      0.0001). In addition, the presence/absence of Helicobacter pylori was independent
      of the normalization of the duodenal mucosa. CONCLUSIONS: In clinical practice
      the criteria for diagnosis of coeliac disease are sufficiently standardized,
      whereas for follow-up they are less well defined. We suggest that in order to
      compare the results from different studies, it should be stated whether remission
      after treatment is based on clinical or histological criteria or both.

PMID- 17448023
TI  - Prostate-specific membrane antigen (PSMA) protein expression in normal and
      neoplastic tissues and its sensitivity and specificity in prostate
      adenocarcinoma: an immunohistochemical study using mutiple tumour tissue
      microarray technique.
AB  - AIMS: To determine prostate-specific membrane antigen (PSMA) expression in normal
      tissues and in 3161 benign and malignant tumours and subsequently to define its
      sensitivity and specificity in prostatic adenocarcinoma (PaC). METHODS AND
      RESULTS: Multiple tissue microarray sections were stained with a monoclonal
      antibody to PSMA. PaC was positive in 93/141 cases (66.0%) with various staining
      patterns including cytoplasmic, apical, apical/cytoplasmic and cytoplasmic with
      membranous accentuation. Of 2174 various tumour types, 154 expressed PSMA,
      including 59/346 (17.0%) urothelial carcinomas of the bladder (UBC). In those
      tumours, the staining pattern was always cytoplasmic. All 846 benign tumours were
      negative for PSMA. The sensitivity and specificity of PSMA in distinguishing PaC
      from any other type of malignancy is 65.9% and 94.5%, respectively. Furthermore,
      its sensitivity and specificity in differentiating PaC from urothelial cancer is
      65.9% and 82.9%, respectively. CONCLUSIONS: Despite its expression by subsets of
      various types of malignancies, PSMA is still considered to be fairly sensitive
      and highly specific for PaC.

PMID- 17448024
TI  - Prognostic significance of Id-1 and its association with EGFR in renal cell
      cancer.
AB  - AIMS: Epidermal growth factor receptor (EGFR) is suggested as one of the positive
      regulators in the invasive progression of renal cell cancer (RCC). Recently, Id-1
      (inhibitor of differentiation or DNA binding), a helix-loop-helix transcription
      factor, has been identified as one of the key factors in the EGFR signalling
      pathway. The aim of this study was to investigate the significance of Id-1
      expression in renal cell cancer and to study its relationship with EGFR. METHODS
      AND RESULTS: Id-1 and EGFR expression was examined in tissue microarray (TMA)
      samples of 107 RCC and 32 normal kidney specimens by immunohistochemistry.
      Relative Id-1 and EGFR protein expression was quantified by estimating the
      staining intensity on a four-grade scale. We found that while negative to weak
      expression of Id-1 and EGFR was observed in non-malignant kidney tissues, most
      RCCs showed significant positive Id-1 and EGFR expression in tumour cells. In
      addition, Id-1 immunostaining intensity was positively associated with increased
      tumour staging, grading and EGFR expression. CONCLUSION: Overexpression of Id-1
      is a novel marker for advanced RCC which is positively correlated with EGFR
      expression. Our results suggest that Id-1 may play an important role in the
      development of RCC and indicate that Id-1 is a potential marker of patients with
      a poor prognosis.

PMID- 17448025
TI  - Expression of beta-catenin and p53 are prognostic factors in deep aggressive
      fibromatosis.
AB  - AIMS: To determine the prognostic significance of beta-catenin in aggressive
      fibromatosis and to identify potential molecular markers for new targeted
      therapies. METHODS AND RESULTS: A tissue microarray of 37 cases of deep
      aggressive fibromatosis was constructed and subjected to immunohistochemical
      analysis for beta-catenin, p53, smooth muscle actin (SMA), desmin, Ki67, c-erbB2,
      epidermal growth factor receptor (EGFR), c-kit, CD34 and S100. Complete clinical
      follow-up was available for 23 patients. Nuclear beta-catenin expression was
      associated with an increased rate of local tumour recurrence (60.0% 1-year and 0%
      5-year event-free survival; P < 0.05). Furthermore, p53 expression was associated
      with an increased risk of tumour recurrence (50% 1-year event-free survival rate
      and 0% 5-years event-free survival rate, P < 0.05). The coexpression of p53 and
      beta-catenin was significantly correlated (P < 0.05). No statistically
      significant association was seen between MIB1 and p53 or beta-catenin expression,
      respectively. No expression of EGFR, c-erbB2 or c-kit was seen. CONCLUSIONS: The
      overexpression of beta-catenin and p53 is associated with a decreased event-free
      survival in deep aggressive fibromatosis. Further studies are required to
      establish whether these findings can lead to an improvement in the treatment of
      this rare neoplasm.

PMID- 17448026
TI  - Distinguishing angioimmunoblastic T-cell lymphoma from peripheral T-cell
      lymphoma, unspecified, using morphology, immunophenotype and molecular genetics.
AB  - AIMS: To identify distinguishing histological, immunophenotypic and molecular
      genetic features between angioimmunoblastic T-cell lymphoma (AITL) and peripheral
      T-cell lymphoma (PTL). METHODS: Nodal T-cell lymphomas examined (n =137),
      included AITL (n = 89), PTL (n = 22), anaplastic large cell lymphoma (n = 16) and
      'AITL/PTL indeterminate' (n = 10) with overlapping features between AITL and PTL,
      showing morphology typical of AITL but lacking follicular dendritic cell
      expansion. Immunohistochemistry for CD3, CD20, CD21 and CD10, in situ
      hybridization for Epstein-Barr virus encoded RNA (EBER) and polymerase chain
      reaction for T-cell and B-cell clonality analysis were performed. RESULTS: Of the
      AITLs, 74/89 showed typical morphology, whereas 15/89 showed hyperplastic
      follicles. AITL and 'AITL/PTL indeterminate' showed a polymorphous infiltrate and
      prominent vascularity in all cases. In both groups, CD10 was present in the
      majority and clear cells and EBER positivity were specific (but not universal)
      features lacking in PTL. Detection of T-cell clonality was significantly higher
      in AITL (90%) compared with PTLu (59%). CONCLUSION: Clear cells and EBV infection
      (when present) are useful distinguishing features and CD10 a sensitive and
      specific marker of AITL. Hyperplastic follicles are present in a significant
      minority of AITL. AITL/PTL indeterminate probably falls within the spectrum of
      AITL rather than PTL.

PMID- 17448029
TI  - Ligneous conjunctivitis: a case report with multiorgan involvement.

PMID- 17448030
TI  - Fibroadenoma occurring in supernumerary breast tissue.

PMID- 17448031
TI  - Invasive solid papillary breast carcinoma with papillary metastasis.

PMID- 17448032
TI  - Immunocytochemical analysis of malignant melanoma of the nasal cavity and sinuses
      using tissue microarray.

PMID- 17448033
TI  - PixelProstate: a simple software program for the measurement of prostate cancer
      volume.

PMID- 17448034
TI  - Primary monophasic synovial sarcoma of the colon.

PMID- 17448035
TI  - Neuromatosis of the bile ducts: a previously un-reported location.

PMID- 17448036
TI  - Cell cycle regulator in primary lung adenocarcinoma and its haematogenous
      metastases.

PMID- 17448037
TI  - Psammoma bodies in medulloblastoma.

PMID- 17448038
TI  - Re: the continued value of central histopathological review of testicular
      tumours.

PMID- 17448041
TI  - The new concept of periodontal disease pathogenesis requires new and novel
      therapeutic strategies.
AB  - In this issue Bostanci et al. (2007) demonstrate that receptor activator of NF
      kappaB ligand (RANKL) and osteoprotegerin (OPG) were oppositely regulated in
      gingival crevice fluid (GCF) from periodontitis patients. RANKL, RANK and OPG are
      key molecules that regulate osteoclast recruitment, differentiation and
      activation. New concepts of the pathogenesis of periodontitis have implicated
      inflammation triggered by host immune response to periodontal biofilm
      microorganisms(s) in disease. Host response to bacteria involves activation of T
      and B cells in the inflammatory infiltrate which bear abundant RANKL that
      promotes osteoclastic bone resorption. Periodontal tissue destruction can be
      ameliorated by immunobiological interference with immune cell RANKL expression or
      function. The new disease concepts provide a foundation to build biological
      approaches to target RANKL production in periodontal lesions.

PMID- 17448042
TI  - Polymorphisms in the CD14 and IL-6 genes associated with periodontal disease.
AB  - AIM: To compare the frequencies of cytokine and receptor molecule genotypes in
      patients with chronic periodontitis with the corresponding frequencies in a
      reference population and to study the relationship between periodontal disease
      severity and polymorphisms in the studied genes. SUBJECTS AND METHODS: CD14, IL
      6, TNF-alpha, IL-10, IL-1alpha, IL-1beta, and TLR-4 polymorphisms of 51
      periodontitis patients were studied using polymerase chain reaction. The genotype
      frequencies in the periodontitis patients and a reference population (n=178) were
      compared. Probing pocket depth (PD), periodontal attachment level (AL), and
      alveolar bone level (BL) were related to the genotypes. RESULTS: No statistically
      significant differences could be found between the frequencies of the cytokine
      genotypes in the periodontitis patients and in the reference group. The extent of
      periodontal disease was higher in subjects with the T-containing genotype of
      CD14(-260) and the GG genotype of IL-6(-174) when compared with the extent in the
      rest of the group. Subjects carrying the composite genotype of the above two were
      most severely affected by periodontal disease. CONCLUSION: According to the
      present results, an evident association exists between the carriage of the T
      containing genotype of CD14(-260) and the GG genotype of IL-6(-174) and the
      extent periodontal disease.

PMID- 17448043
TI  - MMP-2, MMP-9 and TIMP-2 gene polymorphisms in Chinese patients with generalized
      aggressive periodontitis.
AB  - BACKGROUND: Aggressive periodontitis (AgP) has a genetic basis. It has been
      reported that the functional gene polymorphisms of matrix metalloproteinase (MMP)
      2, MMP-9 and tissue inhibitor of metalloproteinase-2 (TIMP-2) alter their
      expressions in transcriptional level and they are involved in the tissue
      destruction of periodontitis. The study was carried out to analyse the
      association of functional polymorphisms in MMP-2, MMP-9 and TIMP-2 with
      generalized AgP (G-AgP) in a Chinese population. MATERIAL AND METHODS: The study
      population consisted of 79 Chinese patients with G-AgP and 128 healthy controls.
      DNA was obtained from oral mucosa swab samples. MMP-2 genotypes were determined
      by PCR-based denaturing high-performance liquid chromatography analysis while MMP
      9 and TIMP-2 genotypes were identified by a PCR-based restriction fragment length
      polymorphism. Chi2 test after Yates' correction was used to investigate the
      possible association of the genotypes with the G-AgP. RESULTS: Although gene
      polymorphisms for MMP-2 and MMP-9 did not show any association with the G-AgP,
      the analysis of the TIMP-2 -418G to C gene polymorphism revealed significant
      differences between the patients and controls. Compared with controls, a
      significant increasing trend of TIMP-2 -418C carrier in the G-AgP patients
      occurred (p=0.013). CONCLUSION: It is suggested that the TIMP2 -418G to C gene
      polymorphism is associated with G-AgP in the Chinese subjects.

PMID- 17448044
TI  - Effect of three different dental health preventive programmes on young adult
      individuals: a randomized, blinded, parallel group, controlled evaluation of oral
      hygiene behaviour on plaque and gingivitis.
AB  - AIM: To evaluate, in young adults, the effect of different preventive programmes
      on oral hygiene and to determine whether the variables investigated are
      predictors of gingival health. MATERIAL AND METHODS: This randomized, blinded,
      parallel, controlled clinical study examined the effectiveness of three dental
      health programmes. Four hundred subjects aged 20-27 years, 211 males and 189
      females, participated in the study. They were recruited from a Public Dental
      Service clinic and from a private dental practice in Jonkoping, Sweden. The
      effect of the programmes on plaque and gingivitis was evaluated over a 3-year
      period. The programmes included activities that were adapted for individuals as
      well as for groups. The plaque indices (PLI) and gingival indices (GI) were used
      to evaluate the programmes. RESULTS: All programmes resulted in a decrease in PLI
      and GI. The greatest decrease was found in the group that was followed-up every 2
      months. Professional tooth cleaning was non-significant for the clinical result.
      Gingival health at baseline, participation in any of the test programmes, and
      knowledge of the dental diseases caries, gingivitis or periodontitis were
      significant predictors of good gingival health. CONCLUSIONS: The study confirms
      the efficacy of three different preventive programmes in reducing supragingival
      plaque and gingival inflammation. Professional tooth cleaning provided no
      clinical benefit beyond that derived from individual and group-based health
      education.

PMID- 17448045
TI  - Influence of bracket design on microbial and periodontal parameters in vivo.
AB  - AIM: To compare undisturbed plaque formation on teeth bonded with different types
      of orthodontic brackets with non-bonded control teeth, via a de novo plaque
      growth experiment over a 7-day period. MATERIAL AND METHODS: A randomized
      controlled trial with split-mouth design was set up enroling 16 dental students.
      Within each subject sites with Speed(S) and GAC(G), brackets and control sites
      were followed. Clinical periodontal parameters were recorded at baseline, on days
      3 and 7. Microbiological samples were taken from the brackets and the teeth on
      days 3 and 7. RESULTS: Both anaerobe and aerobe colony-forming units (CFU) were
      significantly higher in S-sites than in G-sites (p=0.0002, p=0.02). The shift
      from aerobic to anaerobic species was observed earlier in S-sites than in G
      sites. The aerobe/anaerobe CFU ratio was significantly lower in S-sites than in G
      sites (p=0.01). On day 3, the crevicular fluid flow was significantly higher in S
      sites than in control sites (p=0.01). On day 7, S-sites and G-sites showed a
      significantly higher crevicular flow than control sites (both p<0.0001). More
      hypertrophy was seen in S- than in G- and control sites (p=0.05). No significant
      differences for bleeding on probing were observed. CONCLUSION: Bracket design can
      have a significant impact on bacterial load and on periodontal parameters.

PMID- 17448046
TI  - The association between embrasure morphology and central papilla recession.
AB  - OBJECTIVE: To discover the association between embrasure morphology and central
      papilla recession. MATERIAL AND METHODS: The central papilla was visually
      assessed in 330 adults using standardized periapical radiographs of the maxillary
      central incisors. The following vertical distances were measured: papilla
      recession [i.e., the distance from the papilla tip (PT) to the contact point
      (CP)], bone crest (BC) to contact point (BC-CP), proximal cementoenamel junction
      (pCEJ) to contact point (pCEJ-CP), and papilla height (PH). The horizontal
      distance measured was the inter-dental width. Subjects were divided into four
      groups according to inter-dental width and pCEJ-CP distance, respectively: narrow
      long, narrow-short, wide-long, and wide-short. RESULTS: A statistically positive
      relationship was evident between central papilla recession and age, and a
      statistically negative relationship was evident between age and PH in all study
      groups. CONCLUSIONS: Central papilla recession as a result of ageing is most
      frequently associated with a wide inter-dental width and long pCEJ-CP distance.
      However, other factors affect the likelihood of the presence of the inter-dental
      papilla, and further study of the interaction among these factors is warranted.

PMID- 17448047
TI  - Gingival blood flow changes following periodontal access flap surgery using laser
      Doppler flowmetry.
AB  - AIM: To investigate the pattern of gingival blood flow changes following
      periodontal access flap surgery by laser Doppler flowmetry (LDF). MATERIAL AND
      METHODS: Fourteen patients with chronic periodontitis presenting upper anterior
      sites with pocket depth >or=5 mm after initial treatment were included in the
      study. Periodontal access flap surgery was performed on the experimental areas
      and LDF recordings were taken at baseline, following anaesthesia, immediately
      postoperatively and on days 1, 2, 3, 4, 7, 15, 30 and 60 of healing, at nine
      predetermined sites per flap. RESULTS: Significant ischaemia was observed at all
      flap sites following anaesthesia and immediately postoperatively. At the alveolar
      mucosal sites, a peak increase of the gingival blood flow was observed on
      postoperative day 1 (p<0.001), which persisted until day 7 (p=0.012) and resolved
      by day 15. The mucosal sites close to the flap periphery presented higher blood
      perfusion compared with the sites located centrally in the flap. The
      microcirculatory perfusion of the buccal and palatal papillae was maximum on
      postoperative day 7 (p=0.013 and <0.001, respectively) and returned to baseline
      by day 15. CONCLUSION: Topographically distinct areas of the periodontal access
      flap consistently present different patterns of microvascular blood flow
      alterations during the wound-healing period.

PMID- 17448048
TI  - Bone formation at rhBMP-2-coated titanium implants in the rat ectopic model.
AB  - BACKGROUND: The objective of this study was to evaluate local bone formation at
      titanium porous oxide (TPO) implant surfaces adsorbed with recombinant human bone
      morphogenetic protein-2 (rhBMP-2). METHODS: In vitro studies were used to
      estimate the kinetics of I125-labeled rhBMP-2 released from TPO surfaces with
      narrow (N) or open (O) pores. Machined/turned titanium (MT) surfaces served as
      control. The rat ectopic model was used to assess local bone formation. Briefly,
      TPO-N, TPO-O, and MT disc implants adsorbed with 5, 10, or 20 microg rhBMP-2,
      respectively, were implanted subcutaneously into the ventral thoracic region in 5
      week-old male Long Evans rats. The animals were euthanized at day 14 postsurgery
      when implants with surrounding tissues were removed, radiographed, and gross
      observations recorded. The specimens were processed for histologic evaluation
      using conventional cut-and-grind techniques. TPO implants without rhBMP-2
      included in a preliminary evaluation revealed no evidence of bone formation,
      tissue encapsulation, or vascularity, thus such controls were not further used.
      RESULTS: TPO and MT implant surfaces adsorbed with 5 microg rhBMP-2 retained 2.3
      5.4% rhBMP-2 following immersion and rinse in buffer, and 1.1-2.2% rhBMP-2
      following repeated immersions and rinses over 27 days. TPO implants retained the
      most rhBMP-2 and MT implants retained the least. Explants revealed increased hard
      tissue formation, tissue encapsulation, and vascularity at TPO compared with MT
      implants. Radiographic observations were consistent with the explant
      observations. The histologic analysis showed greater amounts of bone formation,
      osteoblastic cells, osteoid, marrow, tissue encapsulation, vascularity, and bone
      voids for implants adsorbed with 10 and 20 microg rhBMP-2, and for TPO implants
      at the 5-microg rhBMP-2 dose. The histometric analysis revealed significantly
      greater bone formation at TPO-O than at MT implants at the 5-microg rhBMP-2 dose.
      All surfaces showed significant bone formation at the 10- and 20-microg dose.
      CONCLUSIONS: rhBMP-2 adsorbed onto TPO implant surfaces executes an
      osteoinductive effect including bone contacting the implant surface. This effect
      is surface- and dose-dependent; the TPO-O surface yielding the most bone at the
      low discriminating rhBMP-2 dose.

PMID- 17448049
TI  - Comprehensive dental therapy (periodontal and exodontia) removes inflammatory
      foci and aids in glycemic control.

PMID- 17448051
TI  - Non-heart-beating organ donation - solution or a step too far?

PMID- 17448052
TI  - Outcome after admission to ITU following out-of-hospital cardiac arrest: are non
      survivors suitable for non-heart-beating organ donation?
AB  - We have reviewed retrospective data from two large UK teaching hospitals
      regarding outcome following out-of-hospital cardiac arrest and the suitability of
      non-survivors for non-heart-beating organ donation. Patients were selected
      retrospectively from consecutive admissions from two intensive care units who had
      presented following out-of-hospital cardiac arrest, to a total of 50 patients in
      each centre. They had all been resuscitated to achieve a spontaneous cardiac
      output at the scene, in transit or after arrival in hospital, and required
      further intensive care support due to cardiovascular, respiratory, or
      neurological impairment. Eighty-six patients (86%) died in the Intensive Care
      Unit and only 14 (14%) survived to discharge from the Unit. A further nine (9%)
      patients died in hospital before discharge home. Four patients (4%) were alive
      after 6 months and three (3%) were alive after 1 year. Fifty-seven (57%) of
      patients had active withdrawal of treatment with only four (4%) being potentially
      suitable for organ procurement having not been excluded because of age, medical
      history or the length of time to die following withdrawal of treatment. Our
      results show that only a small increase in donor organs could be potentially
      achieved from this population. Further work is required to determine whether such
      patients should be considered as non-heart-beating donors.

PMID- 17448053
TI  - Bispectral index values during elective rigid bronchoscopy: a prospective
      observational pilot study.
AB  - Rigid bronchoscopy is associated with a high incidence of haemodynamic
      disturbance and awareness under anaesthesia. Anaesthetic agents are given both to
      attenuate the sympathetic response to bronchoscopy and to prevent awareness. Use
      of the Bispectral index to guide anaesthesia has shown to reduce awareness and
      improve recovery times from general anaesthesia. We undertook a prospective
      observational study of BIS values in 50 patients during routine anaesthesia for
      rigid bronchoscopy. BIS values were found to be between 40-60 during bronchoscopy
      for only 0.5% of the time (0-11.5%[0-98.7%]), median (interquartile range
      [range]). Patients had a BIS < 40 for 99.6% (87.9-100%[0-100%]) of the duration
      of bronchoscopy. We identified one case of possible awareness. Few of our
      patients undergoing general anaesthesia for rigid bronchoscopy had BIS scores in
      the suggested range of between 40 and 60. BIS < 40 was more frequent than in
      previous studies of different surgical populations. There was no difference in
      the BIS values of patients anaesthetised with intermittent boluses or target
      controlled infusions of propofol.

PMID- 17448054
TI  - The optimal dose of remifentanil for intubation during sevoflurane induction
      without neuromuscular blockade in children.
AB  - The optimal dose of remifentanil needed to produce successful intubating
      conditions following inhalation induction of anaesthesia using 5% sevoflurane
      without the use of neuromuscular blocking drugs, was investigated in 25 children
      aged 3-10 years. Sixty seconds after inhalation induction of anaesthesia using
      sevoflurane 5% in 100% oxygen, a predetermined dose of remifentanil was injected
      over 30 s. The dose of remifentanil was determined using the modified Dixon's up
      and-down method (0.2 microg x kg(-1) as a step size). The first patient was
      tested at 1.0 microg x kg(-1) remifentanil. Ninety seconds following the bolus
      administration of remifentanil, the child's trachea was intubated. The optimal
      bolus dose of remifentanil required for successful tracheal intubation was 0.56
      (0.15) microg x kg(-1) in 50% of children during inhalation induction using 5%
      sevoflurane in the absence of neuromuscular blocking drugs. Using probit
      analysis, the 95% effective dose (ED(95)) of remifentanil was 0.75 microg x kg(
      1) (95% confidence limits 0.63-1.38 microg x kg(-1)).

PMID- 17448055
TI  - Impact of Trendelenburg positioning on functional residual capacity and
      ventilation homogeneity in anaesthetised children.
AB  - Trendelenburg positioning, a head-down tilt, is routinely used in anaesthesia
      when inserting a central venous catheter to increase the calibre of the jugular
      or subclavian veins and to prevent an air embolism. We investigated the impact of
      Trendelenburg positioning on functional residual capacity and ventilation
      homogeneity as well as the potential reversibility of these changes by
      repositioning and/or a recruitment manoeuvre in children with congenital heart
      disease. Functional residual capacity and ventilation homogeneity were assessed
      in 20 anaesthetised children between the ages of 3 months and 8 years who
      required central venous catheterisation before undergoing cardiac surgery.
      Functional residual capacity was measured (1) in the supine position, (2) in the
      Trendelenburg position, (3) after repositioning supine and (4) after a
      recruitment manoeuvre to total lung capacity which was performed by manually
      elevating the airway pressure to 40 cmH(2)O for ten consecutive breaths. Adopting
      the Trendelenburg position led to a significant decrease in functional residual
      capacity (median [range]- 12 (6-21)%) and increase in lung clearance index (12 (2
      19)%). Baseline values were not reached after repositioning supine in any patient
      until after a standardised recruitment manoeuvre was performed.

PMID- 17448056
TI  - The effect of cricoid pressure on intubation facilitated by the gum elastic
      bougie.
AB  - Tracheal tube impingement is common during gum elastic bougie facilitated
      intubation and a 90 degrees anti-clockwise rotation of the tube usually relieves
      it. We detail a case where this manoeuvre failed in the presence of cricoid
      pressure. We investigated the effect of cricoid pressure on gum elastic bougie
      facilitated intubation in 120 patients randomly allocated to receive sham cricoid
      pressure (n = 60) or 30 N cricoid pressure (n = 60). Impingement occurred in
      23/60 (38%) with sham cricoid pressure and 36/60 (60%) with 30 N cricoid pressure
      (p < 0.025). Only females showed an increase in impingement with cricoid
      pressure: 29% sham cricoid pressure vs 63% 30 N cricoid pressure, p < 0.01,
      whereas the impingement in males was approximately 60% in both groups. Ninety
      degree anti-clockwise rotation of the tube was successful in all 23 patients
      (100%) with sham cricoid pressure and in 32/36 patients (89%) with 30 N cricoid
      pressure. Releasing cricoid pressure relieved the obstruction in the four cases
      where 90 degrees anti-clockwise rotation of the tube failed. Impingement is
      common and 90 degrees anti-clockwise rotation is highly effective in both the
      presence and absence of cricoid pressure. In a small number of cases, cricoid
      pressure may cause the manoeuvre to fail.

PMID- 17448057
TI  - Manual displacement of the uterus during Caesarean section.
AB  - Ninety ASA 1 and 2 pregnant women with term singleton pregnancies and no maternal
      and fetal complications, scheduled for elective or emergency Caesarean section,
      were randomly allocated to group LT (15 degrees left lateral table tilt, n = 45)
      and group MD (leftward manual displacement, n = 45). Subarachnoid block was
      established with a 25-gauge spinal needle at the L3-L4 interspace using 1.5 ml of
      0.5% hyperbaric bupivacaine. A median sensory level of T6 was observed in both
      groups but the incidence of hypotension was markedly lower in group MD when
      compared to group LT (4.4% vs 40%; p < 0.001) with a significant reduction in
      mean (SD) ephedrine requirement (6 (0) vs 11.3 (4.9) mg; p < 0.001). The mean
      (SD) fall in systolic blood pressure was 28.8 (7.3) mmHg in group LT and 20
      (12.7) mmHg in group MD. The time to maximum fall in systolic blood pressure was
      similar in both groups (4.5 min). We conclude that manual displacement of the
      uterus effectively reduces the incidence of hypotension and ephedrine
      requirements when compared to 15 degrees left lateral table tilt in parturients
      undergoing Caesarean section.

PMID- 17448058
TI  - Comparison of Acute Physiology and Chronic Health Evaluation (APACHE) II score
      with organ failure scores to predict hospital mortality.
AB  - This study compared the performance of the Acute Physiology and Chronic Health
      Evaluation (APACHE) II score with two organ failure scores in predicting hospital
      mortality of critically ill patients. A total of 1311 consecutive adult patients
      in a tertiary 22-bed multidisciplinary intensive care unit (ICU) in Western
      Australia were considered. The APACHE II score had a better calibration and
      discrimination than the Max Sequential Organ Failure Score (Max SOFA) (area under
      receiver operating characteristic (ROC) curve 0.858 vs 0.829), Admission SOFA
      (area under ROC 0.858 vs 0.791), and the first day or cumulative 5-day Royal
      Perth Hospital Intensive Care Unit (RPHICU) organ failure score (area under ROC
      0.858 vs 0.822 and 0.819, respectively) in predicting hospital mortality. The
      APACHE II score predicted hospital mortality of critically ill patients better
      than the SOFA and RPHICU organ failure scores in our ICU.

PMID- 17448059
TI  - Systemic complications after head injury: a clinical review.
AB  - Non-neurological organ dysfunction is common after traumatic brain injury and is
      an independent contributor to morbidity and mortality. It represents a risk
      factor that is potentially amenable to treatment, and early recognition and
      prompt intervention may improve outcome. This article reviews the current
      evidence for the mechanisms and treatment of non-neurological organ dysfunction
      after head injury.

PMID- 17448061
TI  - A wasted opportunity for organ donation.

PMID- 17448062
TI  - A new infusion syringe label system designed to reduce task complexity during
      drug preparation.
AB  - A new safety-orientated drug infusion label was studied and was compared with
      conventional methods by prospectively collecting incident reports from November
      1998 to November 2003. Anaesthetists were asked to return an incident form for
      every anaesthetic (87% response rate), the vast majority indicating that no error
      had occurred. One error was reported with the use of the new label. However, this
      was due to an incorrect patient weight being recorded in the notes, and the dose
      was correct for the information available. Therefore, this data point was not
      included in the analysis. Seven errors were reported in the calculation of dosage
      using conventional infusion labels during 18 491 anaesthetics compared with no
      calculation errors in 10 655 anaesthetics with the new label (p = 0.045, Chi
      squared test). Despite the difficulties of demonstrating significant benefit from
      safety initiatives in medicine, these data suggest that targeted system redesign
      can be effective inreducing error.

PMID- 17448063
TI  - Performance of six types of oxygen delivery devices at varying respiratory rates.
AB  - The administration of a known concentration of oxygen is an important part of
      routine care of the sick patient. Many devices are currently available. The
      actual concentration of oxygen that can be delivered by these devices can be
      affected by several factors, both from the patient as well as the device itself.
      Measuring the F(i)o(2) delivered to the lungs in vivo can be both difficult and
      potentially uncomfortable for the subjects. We constructed a model using a
      resuscitation manikin, a ventilator and a set of bellows to simulate ventilation.
      With this model we tested a series of devices - variable performance, fixed
      performance and high flow - at two fixed tidal volumes. The respiratory rate was
      increased and its effect on the oxygen concentration assessed. Variable
      performance systems such as the Hudson mask deliver a significantly reduced
      oxygen concentration at high respiratory rates. Fixed performance systems
      delivering 24-40% oxygen deliver appropriate oxygen concentrations across the
      range of respiratory rates, whereas those delivering 60% show a reduction in
      performance. High flow systems show no failure of performance at increased
      respiratory rates.

PMID- 17448064
TI  - An evaluation of the filtration performance of paediatric breathing system
      filters at low flows.
AB  - The filtration performance of five different types of filter intended for use in
      paediatric anaesthesia was measured. A total of 120 unused filters (24 samples of
      each filter type) were evaluated. The pressure drop and filtration performance,
      using challenges of sodium chloride particles, were measured for each filter at 3
      l min(-1) and 15 l min(-1). The pressure drop was less at the lower flow; there
      was a wide variation in the pressure drop across some filters. The filtration
      performance of all filter types showed an improvement at 3 l min(-1) compared to
      15 l min(-1). Four filter types had filtration efficiencies greater than 95% at
      15 l min(-1) and greater than 99% at 3 l min(-1). The remaining filter type had a
      filtration efficiency less than 90% at 15 l min(-1) and greater than 95% at 3 l
      min(-1). These levels of performance are comparable to that of breathing system
      filters intended for use in adult anaesthesia using flows representing mean
      inspiratory flow.

PMID- 17448065
TI  - Comparison of the Levitan FPS Scope and the single-use bougie for simulated
      difficult intubation in anaesthetised patients.
AB  - A randomised cross-over study was performed in 34 patients with no evidence of
      airway difficulties, following induction of general anaesthesia, to compare the
      efficacy of the Levitan FPS scope (LFPS) and the single-use bougie for tracheal
      intubation during simulated grade IIIa laryngoscopy. Success rates for
      intratracheal placement of the device, and the time required for insertion and
      tracheal intubation were recorded. Both devices were equally successful (31/34
      for the LFPS vs 29/34 for the bougie) for insertion into the glottis. The mean
      insertion time for the LFPS was statistically longer than that for the bougie
      (4.4-12.5 s) but this difference was not clinically relevant. Intubation times
      were similar between the two devices. Major problems hindering successful
      intubation using the LFPS were the presence of a narrow epiglottic-pharyngeal
      wall space and copious secretions. An inability to maintain the desired shape was
      the principal cause of failure with the bougie.

PMID- 17448066
TI  - Levobupivacaine-induced seizures and cardiovascular collapse treated with
      Intralipid.
AB  - Lipid emulsion has been used in the successful treatment of local anaesthetic
      induced cardiovascular collapse in animals and in two cases of cardiac arrest in
      humans. Previous reports of levobupivacaine toxicity in humans have been
      characterised by neurological signs and symptoms, without serious cardiovascular
      events. We present a case in which presumed intravenous injection of
      levobupivacaine led to neurological and cardiovascular consequences. This was
      treated successfully by resuscitation that included intravenous Intralipid
      infusion.

PMID- 17448067
TI  - Takotsubo syndrome during induction of general anaesthesia.
AB  - A 77-year-old female was admitted in our hospital for uterine prolapse surgery.
      She developed ventricular tachycardia during induction of general anaesthesia and
      after initial symptomatic measures, she was transferred to the coronary care
      unit. Heart failure persisted and electrocardiographic changes mimicking acute
      myocardial infarction appeared. Coronary angiography was normal and left
      ventriculography revealed akinesis of the apical region of the left ventricle and
      apical ballooning during systole, with relative sparing of the base of the heart.
      Complete recovery of left ventricular function occurred 8 days after the initial
      onset of symptoms. A diagnosis of Takotsubo syndrome was made on the basis of
      consistent clinical and laboratory findings, typical echocardiography and
      angiography findings, and reversible course. This case emphasises the importance
      of being aware of uncommon causes of cardiac dysfunction in stressful situations,
      especially during induction of general anaesthesia.

PMID- 17448068
TI  - Self-poisoning with lamotrigine and pregabalin.
AB  - We report a case of intentional overdose in a 29-year-old male with two of the
      newer anti-epileptic agents, lamotrigine and pregabalin. To our knowledge, this
      case report details the highest plasma levels of lamotrigine ever recorded in the
      literature. The patient presented with seizures and a reduced level of
      consciousness. Management of these and subsequent complications centres on
      supportive care in the high dependency and intensive therapy units.

PMID- 17448069
TI  - Assessing the effectiveness of medical student teaching methods.

PMID- 17448070
TI  - Simulator training for novice SHOs.

PMID- 17448072
TI  - Management of emergence agitation.

PMID- 17448074
TI  - Confirming tracheal intubation.

PMID- 17448075
TI  - Death after a sub-Tenon's block.

PMID- 17448077
TI  - The non-flexible 'flexible' laryngeal mask airway.

PMID- 17448078
TI  - Failures of luer-slip syringes.

PMID- 17448079
TI  - Use of the Airtraq laryngoscope for anticipated difficult laryngoscopy.

PMID- 17448081
TI  - Diagnosis of bladder rupture by arterial blood gas analysis.

PMID- 17448082
TI  - Premedication with buccal midazolam in children and in adults with learning
      disabilities.

PMID- 17448083
TI  - Variability in tracheostomy tubes.

PMID- 17448084
TI  - A thyroid cyst mimicking a large neck vein on ultrasound.

PMID- 17448085
TI  - Scotland vs. England: 'Anaesthetic Practitioner' or 'Physician Assistant
      Anaesthesia.

PMID- 17448086
TI  - Trauma training in the UK: is ATLS past its 'sell-by date'?

PMID- 17448087
TI  - Caring for manikins.

PMID- 17448088
TI  - Ultrasound guided posterior approach to the infraclavicular brachial plexus.

PMID- 17448092
TI  - Level of practice for ECG interpretation skills should be 'expert'.

PMID- 17448093
TI  - Emergency department personal protective equipment requirements following out-of
      hospital chemical biological or radiological events in Australasia.
AB  - Recent events have led to a revision in ED equipment, preparedness and training
      for disasters. However, clinicians must still decide when, and what level of
      personal protection is required when a toxic threat exists. If possible, clear,
      simple and achievable protocols are required in such situations. Following an off
      site Australasian chemical biological or radiological incident, current evidence
      indicates that the initial receiving ED staff will be adequately protected from
      all known chemical biological and radiological inhalational threats by wearing a
      properly fitted P2 (N95) mask, or its equivalent. Protection from serious contact
      injury is offered by wearing double gloves, disposable fluid-repellent coveralls
      or gown, eye protection, surgical mask, and ideally, a cap and shoe covers; in
      conjunction with universal precautions and procedures.

PMID- 17448094
TI  - Laryngeal dyskinesia: an under-recognized condition.
AB  - OBJECTIVE: To perform a review of the epidemiology, pathogenesis, clinical
      presentation, diagnosis and management of laryngeal dyskinesia. METHODS: A search
      of the Medline database from 1966 to 2003 was performed. A manual search was
      performed of the references of each article. RESULTS: Laryngeal dyskinesia is a
      respiratory condition characterized by abnormal vocal cord adduction and airflow
      limitation at the level of the larynx in the absence of evidence of local organic
      disease. It typically presents to the ED as wheeze, stridor or apparent upper
      airway obstruction. It occurs across a wide age range, is more common in females,
      and is typically associated with a range of underlying psychopathologies.
      Diagnosis is often delayed and unnecessary emergency treatment such as intubation
      and tracheostomy is not uncommon. Patients are commonly on high-dose steroids and
      are frequent users of the health-care system, often over prolonged periods. There
      are multiple diagnostic features on history and examination, and flexible
      nasendoscopy of the vocal cords in the ED can be used to confirm the diagnosis.
      Treatment options in the ED include sedation and use of continuous positive
      airway pressure. Long-term treatment involves a multidisciplinary approach
      involving respiratory physicians/ear, nose and throat surgeons, speech therapy
      and psychiatry. CONCLUSION: Laryngeal dyskinesia remains an under-appreciated
      cause of respiratory presentations to the ED. Emergency physicians are ideally
      placed to make the diagnosis and initiate appropriate referral for specific
      therapies that have a high level of success.

PMID- 17448095
TI  - Outcomes in patients with an emergency department diagnosis of fever of unknown
      origin.
AB  - OBJECTIVE: To describe the outcomes in patients given an ED diagnosis of fever of
      unknown origin (FUO). METHODS: A retrospective analysis of ED records linked to
      hospital morbidity, mortality and microbiology records of patients presenting to
      Western Australia's teaching hospitals from July 2000 to July 2003. RESULTS:
      There were 3218 presentations diagnosed with FUO, 2049 (63.7%) children (median
      age 1.8 years) and 1169 (36.3%) adults (median age 56.0 years). FUO accounted for
      0.3% of adult and 1.5% of paediatric ED presentations. Overall, 1997 (62.1%, 95%
      confidence interval 60.4-63.8%) were admitted (82% adults vs 50.7% children; P <
      0.001). Adults had a longer median length of stay than children (4 days vs 2
      days; P < 0.001) and a higher proportion of positive blood cultures (admissions
      15.1%vs 4.9%; P < 0.001) commonly with Escherichia coli. Streptococcus pneumoniae
      was the most common organism isolated from children. Of 3053 FUO index
      presentations, 338 (11.1%, 95% confidence interval 10.0-12.2%) re-presented.
      Children were more likely to re-present than adults (13.5% of 1959 vs 6.8% of
      1094; P < 0.001). CONCLUSIONS: Fever of unknown origin is diagnosed less
      frequently in adults than in children. Adult patients are more likely to be
      admitted, have longer lengths of stay and have positive blood cultures. Although
      FUO is diagnosed infrequently in the ED, blood cultures remain useful in the
      evaluation of unexplained fever, particularly in adults as age increases.

PMID- 17448096
TI  - Emergency department staff can effectively resuscitate in level C personal
      protective equipment.
AB  - OBJECTIVE: ED staff are expected to perform resuscitation of trauma victims of
      chemical, biological and radiation incidents while wearing level C personal
      protective equipment (PPE). The present project assessed the subjective
      discomfort, physiological impact and performance of staff wearing PPE. METHODS: A
      paired intervention study of ED staff in a resuscitation scenario comparing task
      performance wearing gown and gloves with PPE. Data were collected using a
      structured self-administered questionnaire and by objective and subjective
      measurements. RESULTS: Seven ED doctors and 11 ED nurses were enrolled. Nine had
      previous PPE training although only one had used PPE clinically. Overall, ED
      staff felt that PPE did not affect their ability to perform trauma resuscitation.
      For individual tasks, staff felt that PPE impaired assessment of pulse, i.v.
      cannulation, i.v. line attachment, use of a mini-jet, bag and mask ventilation,
      and communication. However, the only objective difference in task performance was
      time to control haemorrhage (increase from 38 to 47 s, P = 0.02). PPE was well
      tolerated, with minimal physiological or psychological impact. Staff wore PPE for
      a median of 37 min (interquartile range: 33-38) and estimated that PPE could be
      worn for a further 30 min if required. CONCLUSIONS: ED staff are able to perform
      resuscitation procedures in PPE without adverse physiological effects or impact
      on performance. Subjective concerns regarding task performance were not reflected
      in objective measurements. This might indicate that appropriate training and
      feedback could reduce the negative impression associated with activities
      undertaken while wearing PPE.

PMID- 17448097
TI  - Out of hours non-contrast head CT scan interpretation by senior emergency
      department medical staff.
AB  - OBJECTIVE: To assess the accuracy of 'out of hours' (17.00-08.00 hours) non
      contrast head computed tomography (NCHCT) scan interpretation by senior ED
      medical staff. METHODS: The study was undertaken in an inner-city tertiary
      hospital in Sydney. A sample of 315 consecutive 'out of hours' NCHCT scans was
      compiled from a log book in the Medical Imaging Department and randomized into 21
      sets of 15 scans. The scans were reviewed by emergency physicians and registrars
      recruited for the study and their interpretations were compared with the formal
      radiologist report. RESULTS: Seven emergency physicians and 14 registrars took
      part in the study. Two hundred and eighty-seven ED interpretations were used in
      the 2 x 2 table analysis. The overall observed agreement was 0.67 (95% confidence
      interval [CI] 0.61-0.72), sensitivity 0.57 (95% CI 0.45-0.69), specificity 0.70
      (95% CI 0.64-0.76) and kappa 0.24 (95% CI 0.13-0.36). There were 32 false
      negative interpretations including three small contre coup contusions and three
      subdural haemorrhages. CONCLUSION: 'Out of hours' NCHCT scan interpretation by
      senior ED medical staff is only correct two-thirds of the time. Further education
      for all senior ED staff is indicated to improve our accuracy. The safety of NCHCT
      scan interpretation by senior ED medical staff needs further study.

PMID- 17448098
TI  - Practicality, safety and accuracy of computed tomography coronary angiography in
      the evaluation of low TIMI-risk score chest pain patients: a pilot study.
AB  - OBJECTIVES: The present pilot study aimed to assess the practicality, safety and
      accuracy of performing CT coronary angiography (CT-CA) in the evaluation of acute
      chest pain of patients with low thrombolysis in myocardial infarction (TIMI) risk
      scores. METHODS: The present prospective observational study was undertaken in a
      university teaching hospital between November 2004 and December 2005.
      Participants were a convenience sample of patients admitted to hospital for
      investigation of chest pain with TIMI risk scores <3. Consenting patients
      underwent CT-CA within 48 h of presentation. Outcomes of interest were
      practicality (proportion of diagnostic quality scans obtained and preparation
      time for CT-CA), rate of serious adverse events, and accuracy at the patient
      level using selective coronary angiography as the reference standard. RESULTS:
      Thirty-four patients were recruited. Diagnostic quality scans were obtained in
      26/34 or 76% of patients (four failed CT-CA and four non-diagnostic scans). The
      median CT preparation time was 1.9 h (range 0.17-4.0). No serious adverse events
      were found. Fourteen of those 26 patients with diagnostic CT-CA subsequently had
      selective coronary angiography, of which nine were positive. The sensitivity and
      specificity of CT-CA in identifying patients with significant coronary artery
      disease were 9/9 (100%; 95% confidence interval 72-100%) and 4/5 (80%; 95%
      confidence interval 28-100%), respectively. CONCLUSIONS: The majority of acute
      chest pain patients with low TIMI risk scores were successfully scanned with a 16
      slice CT to produce CT-CA studies with good diagnostic quality and accuracy. No
      major adverse events were found. The place of CT-CA in diagnostic workup for
      chest pain remains to be defined.

PMID- 17448099
TI  - Effect of a holiday service reduction period on a hospital's emergency department
      access block.
AB  - OBJECTIVE: To study the effect of holiday service reductions, consisting of bed
      and theatre closures, in a tertiary paediatric hospital on various measures of ED
      occupancy, including access block. METHODS: Retrospective comparative
      observational study of all 2142 ED attendances during a holiday hospital service
      reduction period (the 'study period'), when the hospital's bed capacity was
      reduced by 17% and all elective operating theatres were closed, and all 4255
      attendances during two control periods at a major tertiary children's hospital,
      using the ED's information system to collect data. The following outcome measures
      were derived from the raw data and compared between the control and study groups:
      proportion of all intended inpatient admissions that were actual inpatient
      admissions; proportion of intended inpatient admissions that were discharged home
      from the ED; proportion of all admissions that were ED admissions; access block,
      that is, the percentage of patients requiring inpatient admission who have a
      total ED time of greater than 8 h; the mean number of patients in the ED at any
      particular minute ('ED occupancy'); median waiting times to reach both the
      general ward and the operating theatre. RESULTS: There were no statistically
      significant differences between the study group and the control group in all of
      the outcome measures except for access block, which showed a 16% relative
      improvement (49.8-41.7%) during the study period when compared with the control
      period (P < 0.01). CONCLUSION: At this hospital, unacceptably high levels of ED
      access block persist both during and outside holiday periods, despite there being
      mild improvement in access block during the holiday period where bed closures
      were balanced against the effect of other service cutbacks (e.g. closing
      operating theatres).

PMID- 17448100
TI  - Accuracy of electrocardiogram interpretation improves with emergency medicine
      training.
AB  - OBJECTIVE: To assess whether electrocardiogram (ECG) interpretation accuracy
      improves with advancing years of emergency medicine training. METHODS: A
      prospective cross-sectional double-blinded study of emergency medicine trainees
      attending teaching sessions in ACEM accredited Victorian hospitals. Subjects
      completed a survey about level of training, rotations completed and ECG training.
      They were then asked for the 'main diagnosis' on 10 clinically significant ECG.
      Those in their fourth year of advanced training onwards, or in active preparation
      for fellowship examination (senior trainees) were compared with trainees in
      earlier years (other trainees). RESULTS: There were 122 trainees surveyed in
      total. In the present study, 48/122 were senior trainees and 74/122 were other
      trainees. The overall accuracy of ECG interpretation was 67.5% (95% confidence
      interval [CI] 63.2-71.8%) for the senior trainees and 49.6% (95% CI 45.2-53.9%)
      for the others. Results for some of the individual ECG were: left bundle branch
      block: 81.3% (95% CI 69.9-92.6%) seniors and 58.1% (95% CI 46.6-69.7%) others;
      ventricular tachycardia: 43.8% (95% CI 29.3-58.2%) seniors and 37.8% (95% CI 26.5
      49.2%) others; and ventricular fibrillation: 70.8% (95% CI 57.6-84.1%) seniors
      and 63.5% (95% CI 52.2-74.9%) others. CONCLUSION: There is an improvement in ECG
      interpretation accuracy with advancing years of emergency medicine training in
      Victoria. There exists, however, a low level of accuracy for some critical ECG
      diagnoses. There is a call by trainees for more formalized and regular ECG
      education to begin earlier in their training.

PMID- 17448101
TI  - Rural hospital generalist and emergency medicine training in Papua New Guinea.
AB  - The present paper describes the role of the hospital generalist in rural Papua
      New Guinea (PNG) and the contribution of emergency medicine training to that
      practice. Generalist practice in Tinsley District Hospital in Western Highlands
      Province is described, with emphasis on emergency surgery and anaesthesia. The
      potential of the PNG emergency medicine training programme for preparing
      generalists is discussed. Tinsley Hospital served a population of 40,000 people,
      with 4000 admissions and 300-400 operations performed annually. Two doctors and
      50 nurses and community health workers provided care with minimal resources. The
      doctors provided supervision and teaching for nurses, community health workers,
      hospital administrators and primary health carers, including on long range
      medical patrols. Over 16 months, doctors performed 243 emergency surgical
      procedures including orthopaedics, general surgery, obstetrics and gynaecology.
      The generalist in rural hospitals is required to perform a wide variety of
      medical tasks in isolated settings yet there is no active postgraduate training
      programme. The Master of Medicine, Emergency Medicine programme includes
      rotations through the major disciplines of surgery, anaesthesia, internal
      medicine, paediatrics, obstetrics and gynaecology. It has the potential to train
      doctors in PNG for a generalist role as graduates will learn the foundations of
      the required skills.

PMID- 17448102
TI  - Managing cardiovascular collapse in severe flecainide overdose without recourse
      to extracorporeal therapy.
AB  - Flecainide overdose can rapidly result in profound cardiovascular collapse, and
      is associated with a relatively high mortality. A case is described where a woman
      with major toxicity and high serum levels was managed without recourse to
      invasive modalities such as cardiopulmonary bypass or extracorporeal therapies.
      Hypertonic sodium bicarbonate is recognized as effective therapy for hypotension
      and arrhythmias. More recent case reports have concentrated on the use of
      cardiopulmonary bypass. In this report and other reports describing successful
      resuscitation, the total dose of sodium bicarbonate is conspicuously higher than
      in reports describing extracorporeal interventions. Sodium bicarbonate should be
      given early in the resuscitation, and re-administered as frequently as required,
      targeting an alkaline pH and improved cardiac output, while accepting
      hypernatraemia. This case demonstrates the maxim that the correct dose of
      hypertonic sodium bicarbonate is 'enough'. Cardiopulmonary bypass support can be
      considered as a salvage therapy.

PMID- 17448103
TI  - Pancreatic injuries in under-age Australian rules footballers.
AB  - Blunt injury to the pancreas is rare in children. It has significant
      physiological effects and can result in death. The most common injury mechanism
      is a high-velocity motor vehicle accident. Bicycle accidents, non-accidental
      injuries and falls can also cause pancreatic injury.(1) Given the protected
      retroperitoneal location of the pancreas, it is not surprising that low-velocity
      injuries are an uncommon cause of pancreatic injury. Over a 12-month period we
      have observed three cases of blunt pancreatic injury, occurring during under-age
      Australian rules football (AFL) matches. These represented a spectrum of injuries
      from 'traumatic pancreatitis' to a devascularized distal pancreas requiring
      initial percutaneous drainage complicated by pseudocyst development requiring
      cyst gastrostomy. AFL is a free flowing game that combines certain attributes of
      soccer and rugby. There is an emphasis on physical contact and high-velocity
      interpersonal collisions are frequent.

PMID- 17448104
TI  - Could bystander first-aid prevent trauma deaths at the scene of injury?
AB  - OBJECTIVE: To identify potentially preventable prehospital deaths following
      traumatic cardiac arrest. METHODS: Deaths following prehospital traumatic cardiac
      arrest during 2003 were reviewed in the state of Victoria, Australia. Possible
      survival with optimal bystander first-aid and shorter ambulance response times
      were identified. Injury Severity Scores (ISS) were calculated. Victims with an
      ISS <50 and signs of life were reviewed for potentially preventable factors
      contributing to death including signs of airway obstruction, excessive bleeding
      and/or delayed ambulance response times. RESULTS: We reviewed 112 cases that had
      full ambulance care records, hospital records and autopsy details in Victoria
      2003. Most deaths involved road trauma and 55 victims had an ISS <50. Twelve
      patients received first-aid from bystanders. Ambulance response times >10 min
      might have contributed to five deaths with an ISS <25. CONCLUSION: Five (4.5%)
      potentially preventable prehospital trauma deaths were identified. Three deaths
      potentially involved airway obstruction and two involved excessive bleeding.
      There is a case for increased awareness of the need for bystander first-aid at
      scene following major trauma.

PMID- 17448105
TI  - Uncommon cause of cardiac arrest in the emergency department.
AB  - A previously healthy 48-year-old woman presented to a peripheral ED with non
      specific signs and symptoms, including vomiting, abdominal cramping, shortness of
      breath, tachycardia and hypertension. Despite supportive measures the patient
      rapidly deteriorated, resulting in a cardiac arrest during an interhospital
      transfer. This required aggressive resuscitation, but without success. The case
      represents a diagnostic dilemma in the ED regarding the diagnosis and initial
      management of the patient's presentation.

PMID- 17448106
TI  - Fatal haemorrhage from a caput medusae: a differential to a stabbing.
AB  - Fatal haemorrhage from caput medusae is reported once previously in the
      literature. We report the case of a 48-year-old man who presented to the ED in
      hypovolaemic shock, with a suspected stab wound to the abdomen. He was
      subsequently found to have exsanguinated from a cutaneous varix secondary to
      chronic liver disease.

PMID- 17448107
TI  - Education links between the Australian rural and tertiary emergency departments:
      videoconference can support a virtual learning community.

PMID- 17448109
TI  - Levosimendan: a new option in acute septic cardiac failure?

PMID- 17448113
TI  - The angiotensin type 1 receptor activates extracellular signal-regulated kinases
      1 and 2 by G protein-dependent and -independent pathways in cardiac myocytes and
      langendorff-perfused hearts.
AB  - The angiotensin II (AngII) type 1 receptor (AT(1)R) has been shown to activate
      extracellular signal-regulated kinases 1 and 2 (ERK1/2) through G proteins or G
      protein-independently through beta-arrestin2 in cellular expression systems. As
      activation mechanisms may greatly influence the biological effects of ERK1/2
      activity, differential activation of the AT(1)R in its native cellular context
      could have important biological and pharmacological implications. To examine if
      AT(1)R activates ERK1/2 by G protein-independent mechanisms in the heart, we used
      the [Sar(1), Ile(4), Ile(8)]-AngII ([SII] AngII) analogue in native preparations
      of cardiac myocytes and beating hearts. We found that [SII] AngII does not
      activate G(q)-coupling, yet stimulates the beta-arrestin2-dependent ERK1/2. The
      G(q)-activated pool of ERK1/2 rapidly translocates to the nucleus, while the beta
      arrestin2-scaffolded pool remains in the cytosol. Similar biased agonism was
      achieved in Langendorff-perfused hearts, where both agonists elicit ERK1/2
      phosphorylation, but [SII] AngII induces neither inotropic nor chronotropic
      effects.

PMID- 17448114
TI  - Differential extracellular signal-regulated kinases 1 and 2 activation by the
      angiotensin type 1 receptor supports distinct phenotypes of cardiac myocytes.
AB  - The angiotensin II (AngII) type 1 receptor (AT(1)R) is a seven-transmembrane
      receptor well established to activate extracellular signal-regulated kinases 1
      and 2 (ERK1/2) by discrete G protein-dependent and beta-arrestin2-dependent
      pathways. The biological importance of this, however, remains obscure.
      Application of the modified analogue [Sar(1), Ile(4), Ile(8)]-AngII ([SII] AngII)
      allowed us to dissect the two pathways of ERK1/2 activation in native cardiac
      myocytes. Although cytosol-retained, the beta-arrestin2-bound pool of ERK1/2
      represents an active signalling component that phosphorylates p90 Ribosomal S6
      Kinase, a ubiquitous and versatile mediator of ERK1/2 signal transduction.
      Moreover, the beta-arrestin2-dependent ERK1/2 signal supports intact
      proliferation of cardiac myocytes. In contrast to G(q)-activated ERK1/2, and in
      keeping with its failure to translocate to the nucleus, the beta-arrestin2
      scaffolded pool of ERK1/2 does not phosphorylate the transcription factor Elk-1,
      induces no increased transcription of the immediate-early gene c-Fos, and does
      not entail myocyte hypertrophy. These results clearly demonstrate the biological
      significance of differential signalling by the AT(1)R. The opportunity to
      separate desirable cardiac myocyte division from detrimental hypertrophy holds
      promise that novel pharmacological approaches will allow targeting of pathway
      specific actions.

PMID- 17448115
TI  - Induction of apoptosis by ginger in HEp-2 cell line is mediated by reactive
      oxygen species.
AB  - Ginger (Zingiber officinale Roscoe, Zingiberaceae) is a commonly used medicinal
      herb throughout the world. Although some studies have demonstrated its antitumour
      activities on cancer cells in vitro and in vivo, the exact mechanism is not fully
      elucidated. Hence, the present study was designed to examine the in vitro
      cytotoxic activities of saline extract prepared from ginger extract on HEp-2 cell
      line. The cytotoxic effect of the drug was confirmed by 3-(4,5-dimethyl thiazol-2
      yl)-2,5-diphenyl tetrazolium bromide assay and cell counting and estimation of
      protein, DNA and RNA. Meanwhile, propidium iodide staining and agarose gel
      electrophoresis were performed for determining the induction of apoptosis. In
      addition, superoxide radical generation, nitrite formation and glutathione
      studies show involvement of free radicals. The present results show that the
      extract exerts dose-dependent suppression of cell proliferation; the IC(50) value
      was found to be 900 microg/ml. At a dose of 250 microg/ml, marked morphological
      changes including cell shrinkage and condensation of chromosomes were observed.
      Agarose gel electrophoresis of DNA from HEp-2 cells treated with 250 microg/ml
      ginger powder for 24 hr showed marked DNA ladder pattern. The involvement of free
      radicals was confirmed by increased superoxide production, decreased nitrate
      formation and depletion of glutathione in ginger-treated cells. Further screening
      of active components using gas chromatography-mass spectrometry analyses showed
      the presence of clavatol, geraniol and pinostrobin in the extract. The results of
      the present study suggest that ginger might be useful as a potential antitumour
      agent.

PMID- 17448116
TI  - Influence of different atropine therapy strategies on fenthion-induced organ
      dysfunction in rats.
AB  - We studied the influence of dose and timing of atropine therapy on fenthion
      induced organ dysfunction. Thirty-six rats were randomized into six groups. All
      rats in the five groups except the control group were intoxicated with fenthion.
      The high-dose atropine group received 2 mg/kg of atropine, whereas the low-dose
      group received 100 microg/kg of atropine every hour for 24 hr. One group received
      2 mg/kg of atropine in the first 4 hr of intoxication while the other group
      received 2 mg/kg of atropine in the last 4 hr before killed, which for all rats
      was 24 hr after intoxication. Pseudocholinesterase and aspartate aminotransferase
      and alanine aminotransferase levels and histopathological markers of lung, brain
      and liver were studied. None of our atropine therapy strategies in this study
      totally prevented harm on the three organs. Although the high dose of atropine
      administered for 24 hr had the least harmful markers for lung, it also had the
      most harmful markers for brain and liver. We did not succeed in finding a unique
      therapy strategy in our models beneficial for all studied organs in fenthion
      intoxication in rats. Atropine administration strategy should be oriented for the
      most affected organ pathology in fenthion intoxication.

PMID- 17448117
TI  - Modulation of ERG channels by XE991.
AB  - In neuronal tissue, KCNQ2-5 channels conduct the physiologically important M
      current. In some neurones, the M-current may in addition be conducted partly by
      ERG potassium channels, which have widely overlapping expression with the KCNQ
      channel subunits. XE991 and linopiridine are known to be standard KCNQ potassium
      channel blockers. These compounds have been used in many different tissues as
      specific pharmacological tools to discern native currents conducted by KCNQ
      channels from other potassium currents. In this article, we demonstrate that ERG1
      2 channels are also reversibly inhibited by XE991 in the micromolar range (EC(50)
      107 microM for ERG1). The effect has been characterized in Xenopus laevis oocytes
      expressing ERG1-2 and in the mammalian HEK293 cell line stably expressing ERG1
      channels. The IC(50) values for block of KCNQ channels by XE991 range 1-65
      microM. In conclusion, great care should be taken when choosing the concentration
      of XE991 to use for experiments on native potassium channels or animal studies in
      order to be able to conclude on selective KCNQ channel-mediated effects.

PMID- 17448118
TI  - Effect of interleukin-10 on tissue damage caused by organophosphate poisoning.
AB  - Organophosphate poisoning is a common cause of severe morbidity and mortality
      among patients admitted to emergency departments. Tissue damages as a consequence
      of organophosphate poisoning are frequently reported, but preventing this
      potentially severe complication has not been the subject of much research. We
      tested whether interleukin-10, a cytoprotective agent, could prevent or diminish
      pathological signs of tissue damages caused by organophosphate poisoning. Thirty
      rats were divided into three equal groups (n = 10). Group 1 (sham) did not
      receive any agent during the experiment. Group 2 (control) received 0.8 g/kg of
      fenthion intraperitoneally, followed by 6 ml/kg of intraperitoneal normal saline
      30 min and 3 hr later. Group 3 (treatment) received 0.8 g/kg of fenthion
      intraperitoneally, followed by 2 microg/kg of interleukin-10 intraperitoneally 30
      min and 3 hr later. All rats were killed under anaesthesia after 6 hr and tissue
      samples were obtained from liver, kidneys and lungs. Even organophosphate
      poisonings do not cause significant clinical problems; several degrees of damages
      could be observed in liver, kidneys and lungs. These damages could be reduced by
      interleukin-10 treatment.

PMID- 17448119
TI  - Protective effects of caffeic acid phenethyl ester, vitamin C, vitamin E and N
      acetylcysteine on vancomycin-induced nephrotoxicity in rats.
AB  - The objective of this study was to compare the beneficial effects of caffeic acid
      phenethyl ester (CAPE), vitamin C, vitamin E and N-acetylcysteine on vancomycin
      induced nephrotoxicity. Thirty rats were randomly devided into six groups: (i)
      control; (ii) vancomycin, 200 mg/kg administrated via intraperitoneal route;
      (iii) vancomycin plus CAPE-vancomycin with 10 micromol/kg CAPE; (iv) vancomycin
      plus vitamin C-vancomycin (intraperitoneally) with 200 mg/dl vitamin C in
      drinking water; (v) vancomycin plus vitamin E-vancomycin with 1000 mg/kg body
      weight vitamin E (intramuscularly); and (vi) vancomycin plus N-acetylcysteine
      vancomycin with 10 mg/kg body weight (intraperitoneally) of N-acetylcysteine.
      Vancomycin treatments were started 1 day after the first administrations of these
      agents and continued for 7 days. At the end of the experiments, catalase activity
      was significantly decreased by vancomycin in kidney homogenates (P < 0.05).
      Vitamin E, vitamin C, N-acetylcysteine and CAPE administrations decreased the
      blood urea nitrogen levels increased by vancomycin, although significant
      differences were detected only in the vitamins E and C groups (P < 0.05).
      Increased renal malondialdehyde and nitric oxide levels by vancomycin were
      significantly suppressed by agents used in the study (P < 0.05).
      Histopathological examination demonstrated prominent damages in the vancomycin
      treated group. Vitamin E was the most beneficial agent on vancomycin-induced
      tubular damage, followed by vitamin C, N-acetylcysteine and CAPE treatments,
      respectively. The data suggest that vitamin E, as well as vitamin C, N
      acetylcysteine and CAPE, could be useful for reducing the detrimental effects on
      vancomycin-induced toxicity in kidneys.

PMID- 17448120
TI  - Evaluation of the effect of cola drinks on bone mineral density and associated
      factors.
AB  - The aim of the study was to determine bone mineral density changes caused by
      consumption of cola drinks and the associated factors. Thirty Sprague-Dawley rats
      were divided into four groups. Groups 1 and 2, consisting of 10 male and 10
      female rats, respectively, were provided with as much food, water and cola drinks
      as they wanted. Groups 3 and 4, consisting of five rats each, received only rat
      chow and water. The bone mineral density of the rats was measured using dual
      energy X-ray absorptiometry at the end of 30 days. The blood values and weights
      of the animals were also determined. The oesophagus and kidneys were removed for
      histopathological examination. The weight gain was higher in the groups consuming
      cola drinks than the control group rats (P < 0.05). Water consumption decreased
      5.9 times while total fluid consumption increased 1.6-1.9 times in the group
      consuming cola drinks. No significant change was detected in the blood calcium
      levels. There was a significant decrease in the bone mineral density of test
      groups when compared to the control groups (P < 0.05). While we did not detect
      any pathological oesophageal changes in the rats consuming cola drinks,
      examination of the kidneys revealed general glomerular congestion and
      intertubular bleeding. We suggest that the decrease in bone mineral density might
      be related to the renal damage caused by cola drinks in addition to other related
      factors.

PMID- 17448121
TI  - Protective action of amlodipine on cardiac negative inotropism induced by
      lipopolysaccharide in rats.
AB  - Amlodipine has been shown to prevent decrease in vascular responsiveness induced
      by injection of Salmonella typhosa lipopolysaccharide (LPS); however, there is no
      study reporting if this protection by amlodipine extends to ventricular
      contractility. Therefore, we have investigated in rat isolated right ventricle
      strips contracted by electrical stimulation (1 and 3 Hz and subsequently 1 Hz)
      whether pre-treatment with amlodipine (15 mg/kg orally for 1 week) precludes the
      decrease in ventricular contractility related to the induction of nitric oxide
      synthase stimulated by LPS injection (4 mg/kg intraperitoneally). The induction
      of septic shock was confirmed in isolated aortic rings from LPS-injected rats by
      verifying that the contractile response to 1 microM noradrenaline had been (i)
      decreased after LPS injection and (ii) markedly potentiated by the addition of 10
      microM l-arginine. The injection of saline to untreated and amlodipine-treated
      rats produced a non-significant effect on right ventricular contractility during
      180 min. at 3 Hz; the recovery of the contractile response was improved when the
      stimulation frequency was subsequently returned to 1 Hz after 30 min. In
      contrast, injection of LPS to untreated and amlodipine-treated rats (amlodipine +
      LPS) produced a decrease in right ventricular contractility during 180 min. at 3
      Hz, an effect that was more pronounced in LPS than in amlodipine-treated rats.
      These ex vivo results obtained after LPS injection suggest that amlodipine may
      have inhibited, at least in part, the induction of nitric oxide synthase with a
      resulting preclusion of the cardiovascular failure produced by septic shock.

PMID- 17448122
TI  - Ferric-reducing ability power of selected plant polyphenols and their
      metabolites: implications for clinical studies on the antioxidant effects of
      fruits and vegetable consumption.
AB  - Undeniably, low sensitivities in the ferric-reducing ability power (FRAP) is
      evident in the detection of the augmentation of plasma antioxidant activity,
      relative to the rise in circulating polyphenols after ingestion of fruits and
      vegetables. We investigated in vitro the FRAP of 17 plant polyphenols and their
      metabolites at submicromolar concentrations commensurate in human plasma. We then
      explored the in vitro effects of polyphenols and purified apple quercetin
      glycosides on plasma FRAP. We found that apple quercetin glycosides along with
      various polyphenols observed this distinct power at submicromolar concentrations.
      The presence of a catechol structure in the compound molecule was positively
      associated with FRAP (r = 0.60, P < 0.05). An aliphatic substitute at a catechol
      ring and a double bond in an aliphatic substitute conjugated with an aromatic
      ring of catechol contributed to 37% of the variance in the FRAP of compounds with
      catechol in the backbone structure (n = 11). Plasma supplementation with 0.2
      microM mixtures of seven of the most active compounds (catechin, 3,4
      dihydroxycinnamic acid, 3,4-dihydroxyhydrocinnamic acid, 3,4
      dihydroxyphenylacetic acid, ferulic acid, gallic acid and quercetin) initiated a
      placid rise in FRAP (23.3 +/- 1.2 versus 28.1 +/- 1.3 nmol of Fe(3+), P < 0.05).
      Apple quercetin glycosides at 0.5 microM did not elevate plasma FRAP. Plasma
      alone had 30 times higher power than quercetin glycosides at 0.5 microM.
      Abounding of FRAP exhibited in human plasma as compared to polyphenols at
      submicromolar concentrations, may offer elucidation to previous incongruities
      implicated in insignificant rises of plasma FRAP several days after ingestion of
      fruits or vegetables. This suggests that intake of food products and/or
      supplements rich in polyphenols containing a catechol ring with an aliphatic
      substitute augments the plasma FRAP in human beings.

PMID- 17448123
TI  - Delayed cardiotoxicity in chronic lithium poisoning: discrepancy between serum
      lithium concentrations and clinical status.
AB  - Chronic lithium poisoning is characteristically associated with greater toxicity
      than acute ingestion. Neurotoxic features may occur within several hours, whereas
      major cardiovascular effects are typically not seen until later. This report
      describes profound bradycardia as a late consequence of chronic lithium
      poisoning, and reminds us to consider the possibility of delayed toxic effects,
      even in situations where serum lithium concentrations appear to be declining.

PMID- 17448124
TI  - Effects of subchronic lithium treatment on levels of BDNF, Bcl-2 and phospho-CREB
      in the rat hippocampus.
AB  - Although it has been proposed that exposure to lithium up-regulates brain-derived
      neurotrophic factor (BDNF), B-cell leukaemia/lymphoma 2 protein (Bcl-2) and
      cyclic AMP-response element-binding protein (CREB), and these molecules are
      involved in the neuroplastic actions and clinical efficacy of the drug, the
      several lines of evidence suggest that the lithium-induced up-regulation of these
      molecules has not been consistently confirmed. Few studies have examined the
      effects of lithium exposure on the regulation of these molecules in the dentate
      gyrus (DG) and area CA1 in the hippocampus. We examined the effects of subchronic
      lithium treatment on the levels of BDNF, Bcl-2 and phosphorylated CREB in the DG
      and area CA1. We administered LiCl intraperitoneally (1 mEq/kg per day) to adult
      rats for 14 days, killed animals in 24 hr after the last administration of the
      drug, and determined the tissue levels of BDNF, Bcl-2 and pCREB in the DG and
      area CA1. Subchronic lithium treatment for 14 days did not significantly alter
      the levels of BDNF, Bcl-2 or phosphorylated CREB in the DG and area CA1 in the
      hippocampus. This study indicates that the lithium-induced up-regulation of these
      molecules may be various depending on the duration of lithium exposure and
      particular brain regions exposed to the drug.

PMID- 17448126
TI  - Distinguishing type 1 and type 2 diabetes at diagnosis. What is the problem?

PMID- 17448128
TI  - Incidence of type 1 diabetes mellitus in the 0- to 17-yr-old Israel population,
      1997-2003.
AB  - BACKGROUND: Recent reports from different countries have shown an increased
      incidence of type 1 diabetes mellitus (T1DM). A national juvenile diabetes
      register was established by the Israel Pediatric Endocrine Society and the Israel
      Center for Disease Control (ICDC) in 1997. OBJECTIVE: This article reports the
      epidemiology of T1DM in children in the age-group 0-17 yr in Israel during 1997
      2003. METHODS: The Israel juvenile diabetes register is a population-based
      anonymous registry. Newly diagnosed cases of all types of diabetes in children
      and adolescents are reported to the ICDC by all the endocrinologists in all the
      pediatric diabetes centers. Overall incidence rates and rates by sex, age, and
      population group are presented. Comparisons are made by year, sex, age, and
      population group. RESULTS: During 1997-2003, 1485 children and adolescents with
      T1DM were reported in the age-group 0-17 yr. The annual incidence rate of T1DM
      increased by 34% during 1997-2003, from 8.0 per 100 000 [95% confidence interval
      (CI) 6.8-9.3] to 10.7 per 100 000 (95% CI 9.4-12.1). Incidence rates were higher
      for Jews than for Arabs. Among Jews, children of Yemenite origin had the highest
      incidence rate (26.1 per 100 000; 95% CI 13.3-38.9). Incidence peaked at an
      earlier age in girls. A first-degree family history of T1DM was found in 9.1% of
      the cases. CONCLUSIONS: The incidence of T1DM is increasing in the Israeli
      population, particularly in the Arab population. The culturally varied
      composition of the Israeli population provides important areas for future studies
      based on data collected in this national register.

PMID- 17448127
TI  - Fasting c-peptide and insulin-like growth factor-binding protein-1 levels help to
      distinguish childhood type 1 and type 2 diabetes at diagnosis.
AB  - BACKGROUND: Children with new onset diabetes (n = 175) were evaluated over 12
      months. Patients were presumptively diagnosed with type 2 diabetes mellitus
      (T2DM) (n = 26) based on obesity, a relative with T2DM, the ability to wean from
      insulin, and absence of glutamic acid decarboxylase-65 (GAD-65) antibodies. We
      hypothesized that markers of insulinization at diagnosis, including fasting C
      peptide and insulin-like growth factor-binding protein (IGFBP)-1, in addition to
      initial CO(2) levels and urine ketones, would help in distinguishing type 1
      diabetes mellitus (T1DM) from T2DM. RESULTS: Children with T1DM (84 male, 65
      female) had a mean age of 8.7 +/- 4.3 yr and a racial background of 78% white,
      19% black, and 3% other. In contrast, children with T2DM (13 female, 13 male) had
      a mean age of 14.2 +/- 3.1 yr with a racial background of 58% black, 27% white,
      and 15% other. Fasting C-peptide level was 0.38 +/- 0.37 ng/mL in T1DM vs. 2.66
      +/- 2.14 ng/mL in T2DM; a C-peptide of 0.85 ng/mL had 83% sensitivity in
      distinguishing T1DM from T2DM. Fasting IGFBP-1 level was 38.1 +/- 39.1 ng/mL
      (T1DM) vs. 3.6 +/- 4.5 ng/mL (T2DM); a value of 3.6 ng/dL could distinguish the
      two types of diabetes with 93% sensitivity. Urinary ketones were found in 79% of
      children with T1DM compared with 56% of those with T2DM, and the magnitude was
      associated with type of diabetes. Initial CO(2) level for T1DM was 17.9 +/- 6.9
      mmol/L vs. 22.7 +/- 5.7 mmol/L for T2DM; a value of 21.5 mmol/L could distinguish
      the two types of diabetes with 83% sensitivity. CONCLUSIONS: In addition to
      obesity, family history of T2DM, and absence of GAD-65 antibodies, children with
      new-onset T2DM may be distinguished from those with T1DM by a combination of
      biochemical parameters (C-peptide, IGFBP-1, CO(2), and urine ketones).

PMID- 17448129
TI  - Marked increase in type 1 diabetes mellitus incidence in children aged 0-14 yr in
      Victoria, Australia, from 1999 to 2002.
AB  - OBJECTIVES: The objectives of the study were to (i) determine the incidence of
      type 1 diabetes mellitus (T1DM) in children aged <15 yr in Victoria, Australia,
      from 1999 to 2002 and (ii) to analyze trends in incidence over this period.
      METHODS: Prospective population-based incidence study. The primary source of case
      ascertainment was from the Australasian Paediatric Endocrine Group (APEG)
      Victorian diabetes register. The secondary source was the National Diabetes
      Register (NDR), which ascertains cases from the National Diabetes Service Scheme
      (NDSS), a Commonwealth government initiative, where patients register to receive
      diabetes supplies at a subsidized price. MAIN OUTCOME MEASURES: Age-standardized
      incidence, trends in incidence by age, sex and year, and variation in incidence
      by region, season, and socioeconomic status. RESULTS: Case ascertainment was
      99.1% complete using the capture-recapture method. The mean annual age
      standardized incidence was 19.3 per 100 000 person years from 1999 to 2002. On
      average, incidence increased by 9.3% per year, with a greater relative increase
      in the 0-4 yr age-group (p = 0.037). No gender bias in incidence was found, but
      the increase in females was statistically significant (13.6% per year, 95%
      confidence interval 3.7-24.3). Variation in geographical distribution and
      seasonal onset of incidence was not statistically significant. CONCLUSIONS: The
      marked increase in the incidence of T1DM in Victoria is greater than that
      recently described in other Australia states and developed nations. The etiology
      of this rise is unclear, while the increased caseload has major implications for
      diabetes health care providers for current and future resource allocation.

PMID- 17448131
TI  - ISPAD Clinical Practice Consensus Guidelines 2006-2007. Insulin treatment.

PMID- 17448132
TI  - ISPAD clinical practice consensus guidelines 2006-2007. Diabetes education.

PMID- 17448134
TI  - Proliferative verrucous leukoplakia and its progression to oral carcinoma: a
      review of the literature.
AB  - BACKGROUND: Proliferative verrucous leukoplakia (PVL) is a distinct clinical form
      of oral leukoplakia defined by its progressive clinical course, changing clinical
      and histopathological features, and potential to develop into cancer. PVL behaves
      in a more aggressive and relentless manner than the more innocuous white oral
      lesions that it can resemble clinically. METHODS: A PubMed search was conducted
      which identified studies that examined patients with PVL and reported data
      meeting inclusion criteria. RESULTS: PVL is seen much more frequently in females
      and most often diagnosed after the sixth decade of life. Tobacco use is not
      strongly linked to the presence of PVL (63% of patients did not use tobacco
      products). Most (74%) of the patients with PVL progressed to oral carcinoma.
      CONCLUSION: PVL is a persistent and progressive oral lesion that requires very
      close follow-up along with early and aggressive treatment to increase the chances
      of a favorable outcome.

PMID- 17448130
TI  - Treatment options for type 2 diabetes in adolescents and youth: a study of the
      comparative efficacy of metformin alone or in combination with rosiglitazone or
      lifestyle intervention in adolescents with type 2 diabetes.
AB  - Despite the increased prevalence of type 2 diabetes mellitus (T2DM) in the
      pediatric population, there is limited information about the relative
      effectiveness of treatment approaches. This article describes the rationale and
      design of a National Institutes of Health-sponsored multi-site, randomized,
      parallel group clinical trial designed to test the hypothesis that aggressive
      reduction in insulin resistance early in the course of T2DM is beneficial for
      prolongation of glycemic control, as well as improvement in associated
      abnormalities and risk factors. Specifically, the trial compares treatment with
      metformin with two alternate approaches, one pharmacologic (combining metformin
      treatment with rosiglitazone) and one combining metformin with an intensive
      lifestyle intervention program. The Treatment Options for Type 2 Diabetes in
      Adolescents and Youth (TODAY) study recruits 800 patients over a 4-yr period and
      follows them for a minimum of 2 yr and maximum of 6 yr. Patients are 10-17 yr of
      age, within 2 yr of diagnosis of diabetes at the time of randomization, lack
      evidence of autoimmunity, and have sustained C-peptide secretion. The primary
      outcome is time to loss of glycemic control, defined as a hemoglobin A1c >8% for
      6 consecutive months. Secondary outcomes include the effect of the alternative
      treatments on insulin secretion and resistance, body composition, nutrition,
      physical activity and fitness, cardiovascular risk monitoring, microvascular
      complications, quality of life, depression, eating pathology, and resource
      utilization. TODAY is the first large-scale, systematic study of treatment
      effectiveness for T2DM in youth. When successfully completed, this study will
      provide critical new information regarding the natural history of T2DM in youth,
      the benefits of initiating early aggressive treatment in these patients, and the
      efficacy of delivering an intensive and sustained lifestyle intervention to
      children with T2DM.

PMID- 17448135
TI  - Oral premalignant lesions: is a biopsy reliable?
AB  - PURPOSE: The purpose of the present retrospective study was to learn whether a
      biopsy of oral premalignant lesions, leukoplakia and erythroplakia, shows
      histopathological findings representative of the whole surgically removed lesion.
      Moreover, to see whether histopathological characteristics of the whole lesion
      are significant for future malignant development after surgery. MATERIALS AND
      METHODS: A total of 101 lesions in 96 patients were included, 42 lesions (41%)
      being homogenous and 50 (50%) non-homogenous leukoplakias, whereas nine (9%) were
      erythroplakias. The lesions were biopsied and subsequently surgically removed on
      the average of 10.4 months after biopsy. Surgical specimens were examined in two
      or more step sections distributed throughout the specimen. The histological
      findings of the biopsies were compared with those of the whole lesions. After
      surgical intervention the patients were followed (mean 6.8 years, range: 1.5
      18.6), and new biopsies taken in case of recurrences. Smokers (73%) were
      encouraged to quit smoking and candidal infections were treated. The possible
      influence of different variables on the risk of malignant development was
      estimated by means of logistic regression analysis. RESULTS: Histological
      examination of the whole lesions showed that seven lesions (7%) harboured a
      carcinoma and 70 lesions (69%) showed a degree of epithelial dysplasia or
      carcinoma in situ. Eleven lesions (12%) developed carcinoma after a mean follow
      up period of 7.5 years. A comparison of the degree of dysplasia in the biopsies
      with that of the whole lesion demonstrated variation with concurrent diagnosis in
      49% of the lesions and in 79% after inclusion of lesions with one degree up or
      down the scale of epithelial dysplasia. CONCLUSION: The estimated odds ratio
      showed that none of the associated variables including presence of any degree of
      epithelial dysplasia in the whole lesion, site, demarcation and smoking had
      influence on the risk of malignant development.

PMID- 17448136
TI  - Frequent high telomerase reverse transcriptase expression in primary oral
      squamous cell carcinoma.
AB  - BACKGROUND: Gene copy number gain of chromosomal arm 5p is frequently found in
      oral squamous cell carcinoma (OSCC) suggesting the activation of proto-oncogenes.
      TERT is a candidate gene encoding for human telomerase reverse transcriptase
      (hTERT). The aim of the present study was to elucidate the relevance of TERT copy
      number gain and high hTERT expression in OSCC. METHODS: Fluorescence in situ
      hybridization (FISH) for TERT and immunohistochemistry (IHC) for hTERT were
      performed to analyze TERT copy numbers and hTERT expression, respectively, on
      tissue microarray (TMA) sections including n = 247 OSCC and n = 105 pharyngeal
      and laryngeal squamous cell carcinomas (PSCC/LSCC). RESULTS: Increased hTERT
      protein expression was more frequently found in OSCC (71.1%, 155/218) than in
      PSCC/LSCC (36.0%, 35/89) (P < 0.001). By contrast, specific TERT amplifications
      were less common in OSCC (2.1%, 4/191) compared with PSCC/LSCC (9.9%, 8/81) (P =
      0.047). CONCLUSIONS: High hTERT expression is a frequent finding in OSCC. It
      might be a promising target for the development of specific anti-neoplastic
      therapy approaches.

PMID- 17448137
TI  - Development of an in vivo mouse model to study oral submucous fibrosis.
AB  - BACKGROUND: Epidemiological data have shown an association of areca nut chewing
      with oral submucous fibrosis (OSF). Experimental evidence to confirm this has
      been limited. Fibrosis-promoting activity of areca nut was tested in an animal
      model. METHOD: Buccal mucosa of a group of 20 female BALB/c strain mice, 10-12
      weeks of age, was treated twice daily 6 days per week with topical application of
      aqueous areca nut extracts for 300-600 days. A control group (n = 20) was treated
      with 50 mM NaCl. The influence of areca nut on the oral epithelium and connective
      tissue was recorded semiquantitatively by light microscopy. RESULTS: The areca
      nut-treated oral epithelium showed progressive changes in epithelial thickness
      leading to atrophy, increased cellularity of fibroblasts, fibrosis of connective
      tissue, focal infiltration of inflammatory cells and muscle atrophy. On killing
      after 600 days of treatment, the scores on cellularity, inflammation and muscle
      atrophy were significantly different to the control group (P = 0.03). CONCLUSION:
      The study provides further evidence that areca nut contributes to the development
      of OSF in treated animals. The model has the potential to test synergism of areca
      nut with other carcinogens and any therapeutic interventions.

PMID- 17448138
TI  - Regional difference in intratumoral lymphangiogenesis of oral squamous cell
      carcinomas evaluated by immunohistochemistry using D2-40 and podoplanin antibody:
      an analysis in comparison with angiogenesis.
AB  - BACKGROUND: Whether tumor cells induce lymphangiogenesis intratumorally or
      permeate pre-existing lymphatic vessels in the peritumoral area still remains
      unclear. In this study, we investigated in detail the intratumoral
      lymphangiogenesis of oral squamous cell carcinomas (SCC) in comparison with tumor
      angiogenesis. METHODS: Immunohistochemistry with D2-40, podoplanin antibody, and
      CD34 antibody were used to evaluate the lymphatic vessel density (LVD) and blood
      microvessel density (MVD). Vascular endothelial growth factor (VEGF) and VEGF-C
      expressions of oral SCC were also assessed by immunohistochemistry. RESULTS: LVD
      significantly increased in the superficial area of tumor tissue compared with
      normal mucosa, whereas it decreased in the deep area of intratumoral tissue near
      the invasion front, in sharp contrast to MVD, which significantly increased
      throughout tumor tissue. Consistent with the decreased intratumoral LVD and
      increased intratumoral MVD, VEGF-C expression of tumor cells was down-regulated
      in the deep area of tumor tissue, while VEGF expression of tumor cells was up
      regulated throughout the tumor tissue. CONCLUSIONS: Lymphangiogenesis in oral SCC
      varies depending on the region within the tumor tissue. It is not induced in the
      genuine tumor stroma near the invasion front, probably due to the down-regulation
      of VEGF-C expression of tumor cells, which is different from VEGF-mediated
      induction of intratumoral angiogenesis.

PMID- 17448139
TI  - Up-regulation of vascular endothelial growth factor in synovial fibroblasts from
      human temporomandibular joint by hypoxia.
AB  - INTRODUCTION: Enhanced expression of vascular endothelial growth factor (VEGF)
      has been described in patients with internal derangement (ID). Herein, we
      examined the expression of VEGF in synovial fibroblasts from temporomandibular
      joint (TMJ) under hypoxia and investigated the regulation of hypoxia-inducible
      factor-1alpha (HIF-1alpha) involved in the expression of VEGF. METHODS: Synovial
      fibroblasts were prepared from human TMJ. These cells were incubated under
      hypoxia or normoxia for the indicated time periods. VEGF levels in cultured
      supernatant were measured by an ELISA. VEGF mRNA isoforms and stability were
      assessed using RT-PCR and Northern blot analysis respectively. HIF-1alpha
      accumulation was evaluated by Western blotting and immunofluorescence. RESULTS:
      VEGF were significantly induced by hypoxia in synovial fibroblasts. In response
      to hypoxia, VEGF121 and VEGF165 mRNA were both remarkably increased, while there
      was no change in VEGF mRNA stability. The accumulation and nuclear translocation
      of HIF-1alpha occurred under hypoxia. CONCLUSIONS: Hypoxia may mainly induce the
      expression of VEGF121 and VEGF165 in synovial fibroblasts to promote inflamed
      angiogenesis of TMJ. HIF-1alpha, which is clearly activated in response to
      hypoxia, may control the expression of VEGF in synovial fibroblasts from TMJ.

PMID- 17448140
TI  - Overexpression of cyclooxygenase-2 correlates with cytoplasmic HuR expression in
      salivary mucoepidermoid carcinoma but not in pleomorphic adenoma.
AB  - BACKGROUND: The overexpression of cyclooxygenase (COX)-2 in several human
      carcinomas suggests that COX-2 is related to carcinogenesis. Although COX-2
      expression has been shown to be up-regulated in carcinomas of the salivary gland,
      its mechanisms are not completely understood. HuR is an mRNA-binding protein that
      controls the stability of certain transcripts including COX-2. METHODS: The
      expression of COX-2 and HuR was determined by immunohistochemistry in 28 cases of
      salivary pleomorphic adenoma and 18 cases of salivary mucoepidermoid carcinoma.
      RESULTS: 28.6% and 72.2% of the pleomorphic adenomas and mucoepidermoid
      carcinomas showed high COX-2 expression respectively. 35.7% of pleomorphic
      adenomas and 72.2% of mucoepidermoid carcinomas were tested positive for HuR in
      the cytoplasm of tumor cells. There was a correlation between a high COX-2
      immunoreactivity and cytoplasmic HuR expression in mucoepidermoid carcinomas but
      not in pleomorphic adenomas. CONCLUSION: This study suggests that cytoplasmic HuR
      is correlated with COX-2 expression in salivary mucoepidermoid carcinomas. In
      addition, the immunoreactivity of COX-2 and cytoplasmic HuR might be used to
      evaluate the nature of a borderline malignancy in the salivary glands.

PMID- 17448141
TI  - Clinico-pathologic correlations of myofibroblastic tumors of the oral cavity. II.
      Myofibroma and myofibromatosis of the oral soft tissues.
AB  - BACKGROUND: Myofibroma is a solitary benign tumor of myofibroblasts.
      Myofibromatosis describes multiple, simultaneous myofibromas at different sites
      in various organs. The clinico-pathologic correlations of
      myofibroma/myofibromatosis confined only to oral soft tissues were analyzed.
      METHODS: In the English language literature, 41 myofibroma and 12 myofibromatosis
      cases involving the oral soft tissues were found. From our files, three new
      myofibroma cases were added. RESULTS: Age at time of diagnosis of oral mucosa
      myofibroma ranged from birth to 70 years (mean 21.7 years), considerably higher
      than myofibroma in other parts of the body. Lesions occurred during the first
      decade (44%) and in the first year of life (17%). Male:female ratio was 1:1.6,
      contrary to the male predominance in other parts of the body. Common sites were
      the tongue (32%) and buccal mucosa (18%). Treatment was local excision, either
      complete (n = 13) or partial (n = 3), wide excision (n = 4), surgery, and
      chemotherapy (n = 1). Myofibromatosis involving oral soft tissues was diagnosed
      at birth in nine (75%) patients, within the first year in two, and as a young
      adult in one. Male:female ratio was 2:1. The tongue was the most common site
      (50%). Half the patients died of disseminated disease within a few days from
      birth, three were cured by partial or complete excision, and three experienced
      spontaneous regression. Histologically, oral mucosa myofibroma/myofibromatosis
      appearance agreed with findings in the literature. CONCLUSIONS: Myofibroma should
      be included in the clinical differential diagnosis of masses of the oral soft
      tissues, especially in the tongue and buccal mucosa of children and adolescents.
      Histological differential diagnosis includes benign and malignant spindle-shaped
      lesions. Treatment of choice is local excision.

PMID- 17448142
TI  - Proliferative verrucous leukoplakia and its progression to oral carcinoma: report
      of three cases.
AB  - Proliferative verrucous leukoplakia (PVL) is a distinct clinical form of oral
      leukoplakia defined by its progressive clinical course, changing clinical and
      histopathologic features, and potential to develop into cancer. PVL behaves in a
      more aggressive and relentless manner than the more innocuous white oral lesions
      that it can resemble clinically. We present three cases of PVL that progressed to
      carcinoma and discuss the histopathologic findings that may either hinder or
      assist in the diagnosis.

PMID- 17448143
TI  - Selection strategies for improved biocatalysts.
AB  - Enzymes have become an attractive alternative to conventional catalysts in
      numerous industrial processes. However, their properties do not always meet the
      criteria of the application of interest. Directed evolution is a powerful tool
      for adopting the characteristics of an enzyme. However, selection of the evolved
      variants is a critical step, and therefore new strategies to enable selection of
      the desired enzymatic activity have been developed. This review focuses on these
      novel strategies for selecting enzymes from large libraries, in particular those
      that are used in the synthesis of pharmaceutical intermediates and
      pharmaceuticals.

PMID- 17448144
TI  - Internalization of PrP106-126 by the formyl-peptide-receptor-like-1 in glial
      cells.
AB  - Recent studies suggest that the formyl-peptide-receptor-like-1 (FPRL1) plays an
      essential role in inflammatory responses in the host defence mechanisms and
      neurodegenerative disorders. Furthermore, it may be involved in proinflammatory
      processes of prion diseases. However, little is known about the induction and
      regulation of PrP106-126-induced receptor endocytosis. We have thus analysed
      whether PrP106-126 increases the activity of phospholipase D (PLD) via FPRL1, an
      enzyme involved in the regulation of the secretion, endocytosis and receptor
      signalling, in glial cells. PLD activity was determined using a
      transphosphatidylation assay and the internalization of PrP106-126, and FPRL1 was
      assessed by fluorescence microscopy and quantified by ELISA. We could show that
      PLD is activated by PrP106-126 both in astrocytes and microglia, and moreover
      that PrP106-126 is rapidly internalized via FPRL1 in astrocytes and microglia
      cells. The determination of receptor activity by extracellular signal-regulated
      kinases 1/2 phosphorylation and cAMP level measurement verified the PrP106-126
      induced activation of FPRL1. FPRL1-mediated PrP106-126 uptake was blocked by the
      receptor antagonist chenodeoxycholic acid. These studies indicate the involvement
      of FPRL1-mediated cellular signalling in PrP106-126-endocytosis and may allow the
      development of therapeutic agents interfering with prion uptake and/or PLD
      function, using either PLD or the FPRL1 as a possible pharmaceutical target.

PMID- 17448145
TI  - Differentiated pattern of sodium channel expression in dissociated Purkinje
      neurons maintained in long-term culture.
AB  - Cerebellar Purkinje neurons in vivo exhibit high frequency and multi-spike action
      potentials with transient (INaT), resurgent (INaR) and persistent (INaP) Na+
      currents arising from voltage-gated Na+ channels, which play important roles in
      shaping the action potentials and electrical activity of these cells. However,
      little is known about Na+ channel expression in cultured Purkinje neurons despite
      the use of in vitro approaches to study these cells. Therefore, GFP-expressing
      Purkinje neurons isolated from transgenic mice were analysed after four weeks in
      culture, when, coincident with distinct axonal and dendritic morphologies,
      cultured Purkinje neurons exhibited dendrite-specific MAP2 expression
      characteristic of polarized neurons. In cell-attached patch clamp recordings, Na+
      currents occurred at significantly higher frequencies and amplitudes in patches
      from the soma and axon than from dendrites, similar to the polarized distribution
      observed in vivo. INaT, INaR and INaP Na+ currents with properties similar to
      those observed in acutely isolated Purkinje neurons were detected in nucleated
      outside-out patches from cultured Purkinje cells. RT-PCR analysis detected
      Nav1.1, Nav1.2 and Nav1.6, but not Nav1.3, Nav1.4, Nav 1.5 or Nav1.8 Na+ channel
      alpha subunit gene expression in cultured Purkinje neurons, as observed in vivo.
      Together, the results indicate that key aspects of Na+ channel expression in
      mature Purkinje neurons in vivo occur in vitro.

PMID- 17448146
TI  - Autoantibodies to alpha-synuclein in inherited Parkinson's disease.
AB  - Neurodegeneration in Parkinson's disease (PD) is accompanied by a local immune
      reaction in the affected brain regions. It is well established that alpha
      synuclein is directly implicated in the pathogenesis of PD. Development of the
      disease is often associated with changes of expression and cellular
      compartmentalisation of this protein; moreover, its oligomers or protofibrils are
      often released to the CSF and plasma of patients. Aggregated alpha-synuclein can
      trigger the activation of microglia; however, its capacity to induce production
      of specific autoantibodies (AAb) has not been assessed. In this study, we
      examined the presence of AAb against synuclein family members in the peripheral
      blood serum of PD patients and control individuals. Presence of AAb against beta
      synuclein or gamma-synuclein showed no association with PD. Multi-epitopic AAb
      against alpha-synuclein were detected in 65% of all patients tested and their
      presence strongly correlated with an inherited mode of the disease but not with
      other disease-related factors. The frequency of the presence of AAb in the
      studied group of patients with sporadic form of PD was not significantly
      different from the frequency in the control group but very high proportion (90%)
      of patients with familial form of the disease were positive for AAb against alpha
      synuclein. We hypothesise that these AAb could be involved in pathogenesis of the
      inherited form of PD.

PMID- 17448147
TI  - Brain insulin system dysfunction in streptozotocin intracerebroventricularly
      treated rats generates hyperphosphorylated tau protein.
AB  - The intracerebroventricular (icv) application of streptozotocin (STZ) in low
      dosage was used in 3-month-old rats to explore brain insulin system dysfunction.
      Three months following STZ icv treatment, the expression of insulin-1 and -2 mRNA
      was significantly reduced to 11% in hippocampus and to 28% in frontoparietal
      cerebral cortex, respectively. Insulin receptor (IR) mRNA expression decreased
      significantly in frontoparietal cerebral cortex and hippocampus (16% and 33% of
      control). At the protein/activity level, different abnormalities of protein
      tyrosine kinase activity (increase in hippocampus), total IR beta-subunit
      (decrease in hypothalamus) and phosphorylated IR tyrosine residues (increase)
      became apparent. The STZ-induced disturbance in learning and memory capacities
      was not abolished by icv application of glucose transport inhibitors known to
      prevent STZ-induced diabetes mellitus. The discrepancy between reduced IR gene
      expression and increase in both phosphorylated IR tyrosine residues/protein
      tyrosine kinase activity may indicate imbalance between
      phosphorylation/dephosphorylation of the IR beta-subunit causing its dysfunction.
      These abnormalities may point to a complex brain insulin system dysfunction after
      STZ icv application, which may lead to an increase in hyperphosphorylated tau
      protein concentration. Brain insulin system dysfunction is discussed as possible
      pathological core in the generation of hyperphosphorylated tau protein as a
      morphological marker of sporadic Alzheimer's disease.

PMID- 17448148
TI  - Differential stimulation-induced receptor localization in lipid rafts for
      interleukin-6 family cytokines signaling through the gp130/leukemia inhibitory
      factor receptor complex.
AB  - Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) are
      cytokines which signal through receptor complexes that include the receptor
      subunits glycoprotein 130 (gp130) and the LIF receptor (LIFR), but CNTF also
      requires the non-signal transducing CNTF receptor (CNTFR) for binding. We show
      here that in IMR-32 neuronal cells endogenously expressing the receptor subunits
      for LIF and CNTF, CNTFR, but not gp130 or LIFR, is found in detergent-resistant
      lipid rafts. In addition, stimulation of these cells with CNTF resulted in a
      rapid translocation of a portion of gp130 and LIFR into detergent-resistant lipid
      rafts while an equivalent stimulation with LIF did not. Disruption of lipid rafts
      by cholesterol depletion of cell membranes blocked the CNTF-induced translocation
      of LIFR and gp130. Interestingly, while cholesterol-depletion did not inhibit
      signal transducer and activator of transcription 3 phosphorylation by either CNTF
      or LIF stimulation, it strongly inhibited both CNTF- and LIF-mediated
      phosphorylation of extracellular signal-regulated kinases 1 and 2 and Akt. LIF
      and CNTF generally appear to have redundant effects in cells responsive to both
      cytokines. Intriguingly, the data presented here suggest a possible mechanism
      whereby CNTF or other cytokines that signal through CNTFR could generate signals
      distinct from those elicited by cytokines such as LIF which utilize a LIFR/gp130
      heterodimer, via association with or exclusion from lipid rafts.

PMID- 17448149
TI  - A human neuronal tissue culture model for Lesch-Nyhan disease.
AB  - Mutations in the gene encoding the purine salvage enzyme, hypoxanthine-guanine
      phosphoribosyltransferase (HPRT) cause Lesch-Nyhan disease, a neurodevelopmental
      disorder characterized by cognitive, neurological, and behavioral abnormalities.
      Despite detailed knowledge of the enzyme's function, the key pathophysiological
      changes that accompany loss of purine recycling are unclear. To facilitate
      delineating the consequences of HPRT deficiency, four independent HPRT-deficient
      sublines of the human dopaminergic neuroblastoma, SK-N-BE(2) M17, were isolated
      by targeted mutagenesis with triple helix-forming oligonucleotides. As a group,
      these HPRT-deficient cells showed several significant abnormalities: (i) impaired
      purine recycling with accumulation of hypoxanthine, guanine, and xanthine, (ii)
      reduced guanylate energy charge and GTP:GDP ratio, but normal adenylate energy
      charge and no changes in any adenine nucleotide ratios, (iii) increased levels of
      UTP and NADP+, (iv) reduced DOPA decarboxylase, but normal monoamines, and (v)
      reduction in cell soma size. These cells combine the analytical power of multiple
      lines and a human, neuronal origin to provide an important tool to investigate
      the pathophysiology of HPRT deficiency.

PMID- 17448150
TI  - The Arctic Alzheimer mutation favors intracellular amyloid-beta production by
      making amyloid precursor protein less available to alpha-secretase.
AB  - Mutations within the amyloid-beta (Abeta) domain of the amyloid precursor protein
      (APP) typically generate hemorrhagic strokes and vascular amyloid angiopathy. In
      contrast, the Arctic mutation (APP E693G) results in Alzheimer's disease. Little
      is known about the pathologic mechanisms that result from the Arctic mutation,
      although increased formation of Abeta protofibrils in vitro and intraneuronal
      Abeta aggregates in vivo suggest that early steps in the amyloidogenic pathway
      are facilitated. Here we show that the Arctic mutation favors proamyloidogenic
      APP processing by increased beta-secretase cleavage, as demonstrated by altered
      levels of N- and C-terminal APP fragments. Although the Arctic mutation is
      located close to the alpha-secretase site, APP harboring the Arctic mutation is
      not an inferior substrate to a disintegrin and metalloprotease-10, a major alpha
      secretase. Instead, the localization of Arctic APP is altered, with reduced
      levels at the cell surface making Arctic APP less available for alpha-secretase
      cleavage. As a result, the extent and subcellular location of Abeta formation is
      changed, as revealed by increased Abeta levels, especially at intracellular
      locations. Our findings suggest that the unique clinical symptomatology and
      neuropathology associated with the Arctic mutation, but not with other intra
      Abeta mutations, could relate to altered APP processing with increased steady
      state levels of Arctic Abeta, particularly at intracellular locations.

PMID- 17448153
TI  - Intestinal bacteria and ageing.
AB  - Advancements in science and medicine, as well as improved living standards, have
      led to a steady increase in life expectancy, and subsequently a rise in the
      elderly population. The intestinal microbiota is important for maintenance of
      host health, providing energy, nutrients and protection against invading
      organisms. Although the colonic microbiota is relatively stable throughout adult
      life, age-related changes in the gastrointestinal (GI) tract, as well as changes
      in diet and host immune system reactivity, inevitably affect population
      composition. Recent studies indicate shifts in the composition of the intestinal
      microbiota, which may lead to detrimental effects for the elderly host. Increased
      numbers of facultative anaerobes, in conjunction with a decrease in beneficial
      organisms such as the anaerobic lactobacilli and bifidobacteria, amongst other
      anaerobes, have been reported. These changes, along with a general reduction in
      species diversity in most bacterial groups, and changes to diet and digestive
      physiology such as intestinal transit time, may result in increased putrefaction
      in the colon and a greater susceptibility to disease. Therapeutic strategies to
      counteract these changes have been suggested in ageing people. These include
      dietary supplements containing prebiotics, probiotics and a combination of both
      of these, synbiotics. Limited feeding trials show promising results with these
      supplements, although further longer-term investigations are required to
      substantiate their use in elderly healthcare fields.

PMID- 17448154
TI  - Microbial biofilms in the human gastrointestinal tract.
AB  - The human gastrointestinal tract contains rich and diverse microbiotas along its
      length. However, while extensive studies have been made on lumenal bacterial
      communities in the gut, less work has been carried out on organisms growing in
      biofilms, where individual groups of bacteria exist in a multiplicity of
      different microhabitats and metabolic niches associated with the mucosa, the
      mucus layer and particulate surfaces in the gut lumen. Bacteria and yeasts also
      occur in biofilms attached to artificial surfaces and devices implanted in the
      host, such as in patients being fed via enteral tubes. Although we are just
      beginning to investigate the composition and metabolic activities of these
      structures, increasing evidence suggests that they are important to the host in
      both health and disease. There is mounting interest in mucosal biofilms in the
      colon, especially with respect to their role in inflammatory bowel disease.
      Because bacteria growing in biofilms are more resistant to antibiotics than
      unattached organisms, it is often difficult to modify the structure and
      composition of these communities, or to eradicate them from the body. However,
      recent work has shown that there is considerable potential to alter the species
      composition of mucosal biofilms in a beneficial way using synbiotics.

PMID- 17448155
TI  - Understanding the effects of diet on bacterial metabolism in the large intestine.
AB  - Recent analyses of ribosomal RNA sequence diversity have demonstrated the extent
      of bacterial diversity in the human colon, and have provided new tools for
      monitoring changes in the composition of the gut microbial community. There is
      now an excellent opportunity to correlate ecological niches and metabolic
      activities with particular phylogenetic groups among the microbiota of the human
      gut. Bacteria that associate closely with particulate material and surfaces in
      the gut include specialized primary degraders of insoluble substrates, including
      resistant starch, plant structural polysaccharides and mucin. Butyrate-producing
      bacteria found in human faeces belong mainly to the clostridial clusters IV and
      XIVa. In vitro and in vivo evidence indicates that a group related to Roseburia
      and Eubacterium rectale plays a major role in mediating the butyrogenic effect of
      fermentable dietary carbohydrates. Additional cluster XIVa species can convert
      lactate to butyrate, while some members of the clostridial cluster IX convert
      lactate to propionate. The metabolic outputs of the gut microbial community
      depend not only on available substrate, but also on the gut environment, with pH
      playing a major role. Better understanding of the colonic microbial ecosystem
      will help to explain and predict the effects of dietary additives, including
      nondigestible carbohydrates, probiotics and prebiotics.

PMID- 17448156
TI  - Modification of an effector strain for replacement therapy of dental caries to
      enable clinical safety trials.
AB  - AIMS: To construct a genetically modified strain of Streptococcus mutans for
      dental caries prevention. The strain has significantly reduced cariogenicity
      owing to a deletion of the entire open reading frame for lactate dehydrogenase,
      and has excellent colonization potential through the production of a natural
      antibiotic called mutacin 1140. For use in human clinical trials, additional
      mutations were introduced to enable rapid elimination of the strain in case of
      adverse side effects and to increase genetic stability. METHODS: Deletion
      mutations were introduced into the dal gene for d-alanine biosynthesis and the
      comE gene for genetic transformation. The resulting strain, A2JM, was tested for
      dependence on exogenous d-alanine and its ability to be eradicated from colonized
      rats. The strain was also tested for its ability to exchange DNA with another
      strain of S. mutans in in vitro and in vivo models. CONCLUSIONS: A2JM was
      completely dependent on exogenous d-alanine, but could colonize the oral cavity
      of rats in low numbers in the absence of dietary d-alanine. Results indicated
      that A2JM can scavenge d-alanine from other plaque bacteria. Lowering of the
      total oral bacterial load through daily application of chlorhexidine enabled
      virtually complete eradication of A2JM. The introduction of the comE gene did not
      significantly decrease the transformability of A2JM in in vitro or in vivo
      models. The addition of a deletion in the comE gene does, nonetheless, provide
      additional safety as it has a very low reversion frequency. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Based on the safety and efficacy profiles established in
      vitro and in animal models, A2JM appears suitable for safe use in human clinical
      trials.

PMID- 17448157
TI  - Impact of antimicrobial residues on gut communities: are the new regulations
      effective?
AB  - Veterinary medicines are subject to a rigorous evaluation with regard to safety,
      efficacy and quality before they are licensed. For drugs used in food producing
      animals, it is necessary to establish what is referred to as the acceptable daily
      intake (ADI), this is defined as an estimate of the amount of a substance,
      expressed on a body weight basis, that can be ingested daily over a lifetime
      without appreciable risk to human health. It is necessary to determine a
      toxicological, pharmacological and microbiological ADI. This article describes a
      recently harmonized guideline that outlines the process for determining the need
      for a microbiological ADI and discusses the test systems that take into account
      the complexity of the human intestinal flora. The described process is used to
      address the effects of antimicrobial drug residues on human intestinal flora for
      regulatory purposes. The guideline does not recommend any one particular system
      for use in regulatory decision making but provides recommendations for a
      harmonized approach to establish a microbiological ADI and offers test options
      rather than specifying a testing regimen. The process and the challenges of this
      new guideline are discussed.

PMID- 17448158
TI  - Microbial analysis of soil and groundwater from a gasworks site and comparison
      with a sequenced biological reactive barrier remediation process.
AB  - AIMS: To investigate the distribution of a polymicrobial community of
      biodegradative bacteria in (i) soil and groundwater at a former manufactured gas
      plant (FMGP) site and (ii) in a novel SEquential REactive BARrier (SEREBAR)
      bioremediation process designed to bioremediate the contaminated groundwater.
      METHODS AND RESULTS: Culture-dependent and culture-independent analyses using
      denaturing gradient gel electrophoresis (DGGE) and polymerase chain reaction
      (PCR) for the detection of 16S ribosomal RNA gene and naphthalene dioxygenase
      (NDO) genes of free-living (planktonic groundwater) and attached (soil biofilm)
      samples from across the site and from the SEREBAR process was applied.
      Naphthalene arising from groundwater was effectively degraded early in the
      process and the microbiological analysis indicated a dominant role for
      Pseudomonas and Comamonas in its degradation. The microbial communities appeared
      highly complex and diverse across both the sites and in the SEREBAR process. An
      increased population of naphthalene degraders was associated with naphthalene
      removal. CONCLUSION: The distribution of micro-organisms in general and
      naphthalene degraders across the site was highly heterogeneous. Comparisons made
      between areas contaminated with polycyclic aromatic hydrocarbons (PAH) and those
      not contaminated, revealed differences in the microbial community profile. The
      likelihood of noncultured bacteria being dominant in mediating naphthalene
      removal was evident. SIGNIFICANCE AND IMPACT OF THE STUDY: This work further
      emphasizes the importance of both traditional and molecular-based tools in
      determining the microbial ecology of contaminated sites and highlights the role
      of noncultured bacteria in the process.

PMID- 17448159
TI  - Microbe-aliphatic hydrocarbon interactions in soil: implications for
      biodegradation and bioremediation.
AB  - Aliphatic hydrocarbons make up a substantial portion of organic contamination in
      the terrestrial environment. However, most studies have focussed on the fate and
      behaviour of aromatic contaminants in soil. Despite structural differences
      between aromatic and aliphatic hydrocarbons, both classes of contaminants are
      subject to physicochemical processes, which can affect the degree of loss,
      sequestration and interaction with soil microflora. Given the nature of
      hydrocarbon contamination of soils and the importance of bioremediation
      strategies, understanding the fate and behaviour of aliphatic hydrocarbons is
      imperative, particularly microbe-contaminant interactions. Biodegradation by
      microbes is the key removal process of hydrocarbons in soils, which is controlled
      by hydrocarbon physicochemistry, environmental conditions, bioavailability and
      the presence of catabolically active microbes. Therefore, the aims of this review
      are (i) to consider the physicochemical properties of aliphatic hydrocarbons and
      highlight mechanisms controlling their fate and behaviour in soil; (ii) to
      discuss the bioavailability and bioaccessibility of aliphatic hydrocarbons in
      soil, with particular attention being paid to biodegradation, and (iii) to
      briefly consider bioremediation techniques that may be applied to remove
      aliphatic hydrocarbons from soil.

PMID- 17448160
TI  - Surface charge influences enterococcal prevalence in mixed-species biofilms.
AB  - AIM: To study the influence of 15 microbial isolates on the prevalence of charge
      heterogeneous and charge-homogeneous Enterococcus faecalis strains, all isolated
      from biliary stents, in mixed-species biofilms. METHODS AND RESULTS: Six
      Enterococcus faecalis strains were paired with 15 other microbial isolates to
      form mixed-species biofilms in a microtitre plate assay. Charge-heterogeneous
      Enterococcus faecalis strains display two subpopulations with different surface
      charges, expressed as a biomodal zeta potential distribution. It was found that,
      in general, the prevalence of the charge-heterogeneous, biofilm forming
      Enterococcus faecalis was reduced in mixed-species biofilms. The prevalence of
      charge-homogeneous, nonbiofilm-forming Enterococcus faecalis strains was
      increased only in the presence of Citrobacter freundii BS5126, Stenotrophomonas
      malthophilia BS937, and Candida lusitaniae BS8256, all of which introduced
      sizeable charge heterogeneity in the mixed microbial population. CONCLUSIONS:
      Charge-homogeneous Enterococcus faecalis strains are stimulated to form biofilm
      only by the presence of another microbial species with a considerably less
      negative zeta potential, thereby creating a charge-heterogeneous microbial
      population. SIGNIFICANCE AND IMPACT OF THE STUDY: Enterococcus faecalis is one of
      the predominant species isolated from mixed-species biofilms in clogged biliary
      stents. The current study shows how charge-homogeneous Enterococcus faecalis
      strains form more biofilm in the presence of other microbial species.

PMID- 17448161
TI  - Intralaboratory validation according to the EN ISO 16 140 Standard of the Vidas
      SET2 detection kit for use in official controls of staphylococcal enterotoxins in
      milk products.
AB  - AIM: Immunological tools used to detect staphylococcal enterotoxins (SEs) in
      foods are numerous. The aim of this study was to evaluate, on naturally
      contaminated milk product samples, the performance of the Vidas SET2, in
      comparison to the Transia plate SET. METHODS AND RESULTS: The Vidas SET2 was
      compared with the Transia plate SET on supernatants of Staphylococcus aureus
      isolates and on naturally contaminated milk products. It is noteworthy that when
      using IgG rabbit treatment, both kits can be considered as equivalent to detect
      enterotoxins in naturally contaminated milk products. CONCLUSIONS: This study
      demonstrated that the Vidas SET2 performance is similar to that of Transia plate
      SET kit, when a rabbit IgG treatment step is used before detection step. This
      additional treatment significantly decreased, from 42% to 8%, the rate of
      positive deviations observed using the Transia plate SET detection kit.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The Vidas SET2 was clearly found as more
      specific, when no preliminary rabbit IgG treatment was used, and which results in
      a better workflow when a large number of samples have to be analysed within a few
      days. Considering the results obtained, the Vidas SET2 detection kit can be used
      to assess the safety of milk products for SEs.

PMID- 17448162
TI  - Effect of pH, temperature and nutrient limitations on growth and leukotoxin
      production by Mannheimia haemolytica in batch and continuous culture.
AB  - AIMS: Quantification of the effects of pH, temperature and nutrient limitations
      on the growth and leukotoxin (LKT) production parameters of Mannheimia
      haemolytica in batch and chemostat culture. METHODS AND RESULTS: Mannheimia
      haemolytica strains OVI-1 and PH12296 were grown aerobically in two semi-defined
      media. In amino acid-limited cultures, the LKT concentration and yield in terms
      of biomass (Y(LKT/x)) were up to eightfold greater than in carbon-limited
      cultures. Supplementing amino acid-limited chemostat cultures with cysteine,
      glutamine, ferric iron and manganese further enhanced the Y(LKT/x) values up to
      threefold. Supplementation of an amino acid-limited batch culture of M.
      haemolytica strain OVI-1 with these nutrients resulted in an LKT concentration of
      1.77 g l(-1) that was 45-fold greater than that obtained in RPMI 1640 medium.
      Aerobiosis enhanced LKT production. High acetic acid concentrations were produced
      under carbon-sufficient conditions. The highest maximum specific growth rates
      were recorded in the range of pH 6.8 to 7.8 and 37 to 40 degrees C. CONCLUSIONS:
      An amino acid-limited culture medium greatly improved LKT production in aerobic
      batch culture, which could be further enhanced by supplementation with cysteine,
      glutamine, ferric iron and manganese. SIGNIFICANCE AND IMPACT OF THE STUDY: It
      was demonstrated that LKT production by M. haemolytica could be dramatically
      increased through manipulation of the culture medium composition, which could
      benefit the production of LKT-based vaccines against bovine shipping fever
      pneumonia.

PMID- 17448163
TI  - ACC deaminase from Pseudomonas fluorescens mediated saline resistance in
      groundnut (Arachis hypogea) plants.
AB  - AIM: To study the effect of 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase
      from Pseudomonas fluorescens against saline stress under in vitro and field
      conditions in groundnut (Arachis hypogea) plants. METHODS AND RESULTS: Four plant
      growth-promoting rhizobacteria (PGPR) strains were used in this study to evaluate
      their efficacy in groundnut plants against saline stress under in vitro. Among
      the four PGPR strains used, Ps. fluorescens strain TDK1 showed greater
      performance in improving the plant growth parameters of groundnut seedlings in
      vitro. PCR amplification using Pseudomonas-specific 16S-23S rRNA internal
      transcribed spacers (ITS) primers revealed that all the four strains belonged to
      the group of fluorescent pseudomonads. ITS region of Ps. fluorescens strain TDK1
      was cloned and sequenced. ACC deaminase activity using biochemical and molecular
      (PCR) analysis revealed that among all the four strains, Ps. fluorescens strain
      TDK1 showed greater amount of ACC deaminase activity and positive reaction to PCR
      amplification. ACC deaminase gene from Ps. fluorescens strain TDK1 was isolated,
      cloned and sequenced. Pseudomonas bioformulations were developed and they were
      tested in groundnut plants under saline-affected soils. The results indicated the
      superior performance by Ps. fluorescens strain TDK1 possessing ACC deaminase
      activity in improving yield parameters in groundnut plants despite salinity.
      CONCLUSIONS: Pseudomonas fluorescens strain TDK1 possessing ACC deaminase
      activity enhanced the saline resistance in groundnut plants, which in turn
      resulted in increased yield when compared with the groundnuts treated with
      Pseudomonas strains not having ACC deaminase activity. SIGNIFICANCE AND IMPACT OF
      THE STUDY: The promising role of ACC deaminase from Ps. fluorescens strain TDK1
      in alleviating saline stress has been concluded in groundnut plants. This study
      will be useful for exploiting the activity of ACC deaminase from microbial
      strains against various biotic and abiotic stresses wherever ACC accumulated as
      precursor for ethylene biosynthesis.

PMID- 17448164
TI  - Virulence traits associated with verocytotoxigenic Escherichia coli O157
      recovered from freshwater biofilms.
AB  - AIM: To investigate whether epilithic biofilms in freshwater streams in a mixed
      UK agricultural river catchment harbour Escherichia coli O157, and if so, whether
      they demonstrate an association with those excreted by grazing farm animals.
      METHODS AND RESULTS: Flint shingle, native to the study site, was used as a
      surface for biofilm development within cages of metal lath set into a stream bed
      at four locations on a chalkland farm. Shingle was collected from all sites once
      a month, as were pooled faecal samples from five farm animal populations.
      Subpopulations of E. coli, including E. coli O157 that demonstrated significant
      phenotypic and genotypic similarity with animal faecal isolates (t-test, P =
      0.05) were isolated. Of 1002 E. coli isolates from biofilms and animal faeces, 48
      were confirmed as the O157 strain by latex agglutination. The presence of five
      virulence traits associated with incidence of human disease was tested using PCR.
      Stx(2) was the most frequently isolated single gene (30 isolates), while stx(1)
      was the least frequently recovered (four isolates). CONCLUSION: Escherichia coli
      O157, expressing up to four virulence factors associated with human disease,
      reside within freshwater biofilms in this agricultural environment. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Aquatic biofilms may potentially act as a reservoir for
      these pathogens, and the implications of the findings for the protection of
      drinking water resources should be further investigated.

PMID- 17448165
TI  - The effect of copper concentration on the virulence of pathogenic Vibrio harveyi.
AB  - AIM: To demonstrate the influence of copper on luminescence and toxin production
      in Vibrio harveyi. METHODS AND RESULTS: The effect of copper concentration on the
      expression of both luminescence and toxin of V. harveyi was investigated. Copper
      concentration of less than 40 ppm had no effect on the growth. While V. harveyi
      cultured with 40 ppm copper concentration showed decreased luminescence as
      measured by spectrofluorophotometer and as observed. LuxD gene, which is related
      to luminescence expression, was monitored using real-time RT-PCR. Result showed
      that the concentration of cDNA coding for luxD was lower in V. harveyi with
      copper. Toxic activity against both HeLa cells and shrimp haemocytes was also
      lower in the culture supernatant of V. harveyi grown with 40 ppm copper
      concentration. Moreover, V. harveyi extracellular proteins were analysed using
      SDS-PAGE. Results showed that culture supernatant from V. harveyi grown without
      copper had thicker band indicating a higher concentration of the putative
      cysteine protease, one of the major toxin of V. harveyi. CONCLUSIONS: This study
      proved that both luminescence and toxin were repressed by copper. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The current study demonstrated that copper inhibited
      expression of phenotype of V. harveyi. Furthermore, it may inhibit quorum sensing
      of V. harveyi.

PMID- 17448166
TI  - Phylogenetic analysis of intestinal bacteria and their adhesive capability in
      relation to the intestinal mucus of carp.
AB  - AIMS: The aims of the present study are to characterize the intestinal microbial
      community displaying a high-adhesive capability in fish, and to evaluate the
      relationship between mucosal adhesion of intestinal bacteria and fish health and
      disease. METHODS AND RESULTS: A total of 707 aerobic bacteria isolated from carp
      intestine that were maintained under either feeding (feeding group) or no-feeding
      (no-feeding group) conditions and were performed adhesive assay. Isolates were
      divided into three categories on the basis of adhesive capability: high-, medium
      , and low- adhesive capabilities. The average proportions of isolates with high
      adhesive capability in the feeding and no-feeding groups were 30% and 32%,
      respectively. A phylogenetic analysis using a partial 16S rRNA gene demonstrated
      that most isolates with high-adhesive capability in both groups were classified
      as belonging to an Aeromonas group, and populations of isolates within high- and
      low-adhesive categories were markedly different. CONCLUSIONS: Intestinal bacteria
      with a high-adhesive capability in relation to intestinal mucous always colonize
      on the surface of intestinal mucosa and grow in the intestinal tract of feeding
      carp. The adhesive capability of intestinal bacteria is essential for
      colonization and growth in the intestinal tract of fish. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Our results indicate that members of the Aeromonas group with
      adhesive capability always colonize on the surface of intestinal mucosa.

PMID- 17448167
TI  - Biodegradation of polychlorinated biphenyls in Aroclor 1232 and production of
      metabolites from 2,4,4'-trichlorobiphenyl at low temperature by psychrotolerant
      Hydrogenophaga sp. strain IA3-A.
AB  - AIMS: To determine the extent and pattern of degradation of polychlorinated
      biphenyls (PCBs) in Aroclor 1232 at 5 degrees C by a psychrotolerant bacterium,
      and to confirm the formation of intermediates of PCB metabolism at low
      temperature using 2,4,4'-trichlorobiphenyl (2,4,4'-TCB). METHODS AND RESULTS: 10
      ppm of Aroclor 1232 or 100 micromol l(-1) 2,4,4'-TCB was incubated with biphenyl
      grown cells at 5 degrees C or 30 degrees C for 48 or 72 h. Degradation of PCBs
      and the products of metabolism of 2,4,4'-TCB were confirmed by gas chromatography
      and mass spectrometry. Extents of degradation of many of the PCBs were similar at
      5 degrees C and 30 degrees C. The extent of biodegradation of PCBs in Aroclor
      1232 at 5 degrees C was dependent on chlorination pattern. The 14 chlorine
      containing intermediates of 2,4,4'-TCB metabolism, which were detected, include
      several isomers of dihydrodiols, dihydroxy compounds and meta-cleavage compounds.
      CONCLUSIONS: The bacterium will be useful for bioremediation of PCB-contaminated
      sites in cold climates; however, knowledge of the products of PCB metabolism is
      necessary, as they could be more toxic than the parent compounds. SIGNIFICANCE
      AND IMPACT OF THE STUDY: Substantial degradation of some PCBs in Aroclor 1232 was
      demonstrated at low temperature within 48 h. The detection of several isomeric
      intermediates suggests that multiple pathways are used to transform PCBs in this
      strain. For the first time, formation of metabolic products from 2,4,4'-TCB at
      low temperature is confirmed.

PMID- 17448168
TI  - Competitive exclusion against Salmonella Enteritidis in layer chickens by yoghurt
      microbiota: impact on egg production, protection and yolk-antibody and
      cholesterol levels.
AB  - AIMS: This work aims at studying the impact of competitive exclusion of
      Salmonella serotype Enteritidis infection in layer chickens, by microbiota of
      fresh and dried-modified yoghurt, on egg production and weight, protection
      against infection, and on yolk-antibody and cholesterol levels. METHODS AND
      RESULTS: Four groups of 27-week-old layer chickens were included in this study.
      After an initial enrofloxacin treatment, groups 1 and 2 were administered fresh
      or dry yoghurt (respectively) for 14 days. Groups 1, 2 and 3 were challenged
      intraoesophageally with Salm. Enteritidis, on the sixth day of yoghurt
      administration, while group 4 was left unchallenged and without yoghurt
      administration. No significant difference in percent infectivity of visceral
      organs with Salm. Enteritidis was observed between the groups. The yoghurt
      administered groups showed an early significant antibody response in their yolk
      on the seventh day postchallenge (P < 0.05) and highest egg production and
      weight. Finally, the egg yolk cholesterol concentration was higher in Salm.
      Enteritidis-challenged groups than that observed in the unchallenged group.
      CONCLUSIONS: The results point to the possible involvement of yoghurt
      administration in immunopotentiation and improvement of egg production and
      weight. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings warrant further
      research that could improve immunity and production in layer chickens infected
      with Salm. Enteritidis.

PMID- 17448169
TI  - In vivo gene delivery and expression by bacteriophage lambda vectors.
AB  - AIMS: Bacteriophage vectors have potential as gene transfer and vaccine delivery
      vectors because of their low cost, safety and physical stability. However, little
      is known concerning phage-mediated gene transfer in mammalian hosts. We therefore
      performed experiments to examine phage-mediated gene transfer in vivo. METHODS
      AND RESULTS: Mice were inoculated with recombinant lambda phage containing a
      mammalian expression cassette encoding firefly luciferase (luc). Efficient, dose
      dependent in vivo luc expression was detected, which peaked within 24 h of
      delivery and declined to undetectable levels within a week. Display of an
      integrin-binding peptide increased cellular internalization of phage in vitro and
      enhanced phage-mediated gene transfer in vivo. Finally, in vivo depletion of
      phagocytic cells using clodronate liposomes had only a minor effect on the
      efficiency of phage-mediated gene transfer. CONCLUSIONS: Unmodified lambda phage
      particles are capable of transducing mammalian cells in vivo, and may be taken up
      -- at least in part -- by nonphagocytic mechanisms. Surface modifications that
      enhance phage uptake result in more efficient in vivo gene transfer. SIGNIFICANCE
      AND IMPACT OF THE STUDY: These experiments shed light on the mechanisms involved
      in phage-mediated gene transfer in vivo, and suggest new approaches that may
      enhance the efficiency of this process.

PMID- 17448170
TI  - Heterologous expression of enterocin AS-48 in several strains of lactic acid
      bacteria.
AB  - AIMS: Enterococcus faecalis produces a cationic and circular enterocin, AS-48, of
      7149 Da, the genetic determinants of which are located within the pMB2 plasmid.
      We have compared enterocin AS-48 production by different enterococci species with
      that of other 'safe' lactic acid bacteris (LAB) (GRAS status) and looked into the
      subsequent application of this enterocin in food production. METHODS AND RESULTS:
      In an effort to exploit this system for the heterologous expression of enterocin
      AS-48, a number of vectors containing the as-48 cluster were constructed and used
      to transform several LAB strains (genera Enterococcus, Lactococcus and
      Lactobacillus) CONCLUSION: Heterologous production of enterocin AS-48 failed when
      bacteria other than those belonging to the genus Enterococcus were used as hosts,
      although expression of a partial level of resistance against AS-48 were always
      detected, ruling out the possibility of a lack of recognition of the enterococcal
      promoters. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results reveal the special
      capacity of species from the genus Enterococcus to produce AS-48, an enterocin
      that requires a post-transcriptional modification to generate a circular peptide
      with a wide range of inhibitory activity against pathogenic and spoilage
      bacteria. Preliminary experiments in foodstuffs using nonvirulent enterococci
      with interesting functional properties reveal the possibility of a
      biotechnological application of these transformants.

PMID- 17448171
TI  - Isolation and characterization of a xanthan-degrading Microbacterium sp. strain
      XT11 from garden soil.
AB  - AIMS: Isolation and characterization of the xanthan-degrading Microbacterium sp.
      XT11. METHODS AND RESULTS: The bacterial isolate XT11, capable of fragmenting
      xanthan, has been isolated from soil sample. Morphological and biochemical
      analyses, as well as 16S rRNA gene sequence comparisons, demonstrated that strain
      XT11 should be grouped in the genus Microbacterium, and represented a new member
      in this family. Xanthan could be degraded by the xanthan-degrading enzyme
      released from strain XT11. It has been shown that xantho-oligosaccharides
      fragmented from xanthan had both elicitor activity and antibacterial effect
      against Xanthomonas campestris pv. campestris. CONCLUSIONS: The xanthan-degrading
      enzyme produced by the newly isolated XT11 could fragment xanthan to form
      oligosaccharides. SIGNIFICANCE AND IMPACT OF THE STUDY: Xanthan-degrading
      products would be useful for potential application in the control of black rot of
      cruciferous plants caused by X. campestris pv. campestris and, as an
      oligosaccharide elicitor, in making these plants resistant to disease.

PMID- 17448172
TI  - The potential for beach sand to serve as a reservoir for Escherichia coli and the
      physical influences on cell die-off.
AB  - AIMS: The Escherichia coli burden at a Great Lakes urban beach was evaluated
      during the summer months to determine if sand served as a reservoir for E. coli,
      and if there was evidence of cell replication in situ. Field and laboratory
      studies investigated the effects of moisture, temperature and UV on E. coli
      densities in the sand. METHODS AND RESULTS: Sand samples (n = 481) were collected
      across three distinct transects of the beach, the top, a middle streamline, and
      the berm, over 15 sample days. The highest levels were found in the middle
      streamline, which was affected by stormwater discharge from nearby outfalls and
      roosting gulls; daily geometric mean levels of these seven sites ranged from 6700
      to 40,900 CFU per 100 g of sand. Escherichia coli levels were greatest in samples
      with moisture levels between 15% and 19%, and were significantly higher than 0-4
      and 20-24% ranges (P < 0.05). Pre- and post-rain samples at the beach
      demonstrated an increase in E. coli levels nearly 100-fold within 30 min,
      suggesting sand washout as a major mechanism for loading of E. coli into the
      beach waters. Rep PCR analysis of 160 isolates obtained from eight sites
      demonstrated that 21% of the isolates fell into one of the six clonal patterns,
      suggesting that bacteria may be able to replicate and possibly colonize beach
      sand. Sand field plots inoculated with E. coli cells containing pGFPuv that
      expresses GFP (green fluorescent protein) as a marker showed an initial two- to
      100-fold increase at 24 h, depending on the temperature condition. The sand
      appeared to provide considerable protection from UV exposure as no significant
      difference was seen in cell densities within the first 2-4 cm of sand between
      exposed and unexposed plots (P < 0.05). CONCLUSIONS: Beach sand may act as a
      reservoir for E. coli. Replication of cells appears to be one possible
      contributing factor to the persistently high levels, as indicated by both field
      studies and laboratory studies, and warrants further investigation. Moisture
      content of sand may also be a determinant of cell persistence in the sand
      environment. SIGNIFICANCE AND IMPACT OF THE STUDY: Escherichia coli is used as an
      indicator organism for faecal pollution at most Great Lakes coastal beaches;
      therefore, a better understanding of how E. coli might survive, or possibly
      replicate, in the environment would improve interpretation of beach monitoring
      results.

PMID- 17448173
TI  - L-asparaginase production by isolated Staphylococcus sp. - 6A: design of
      experiment considering interaction effect for process parameter optimization.
AB  - AIMS: Evaluation of fermentation process parameter interactions for the
      production of l-asparaginase by isolated Staphylococcus sp. - 6A. METHODS AND
      RESULTS: Fractional factorial design of experimentation (L18 orthogonal array of
      Taguchi methodology) was adopted to optimize nutritional (carbon and nitrogen
      sources), physiological (incubation temperature, medium pH, aeration and
      agitation) and microbial (inoculum level) fermentation factors. The experimental
      results and software predicted enzyme production values were comparable.
      CONCLUSION: Incubation temperature, inoculum level and medium pH, among all
      fermentation factors, were major influential parameters at their individual
      level, and contributed to more than 60% of total l-asparaginase production.
      Interaction data of selected fermentation parameters could be classified as least
      and most significant at individual and interactive levels. Aeration and agitation
      were most significant at interactive level, but least significant at individual
      level, and showed maximum severity index and vice versa at enzyme production.
      SIGNIFICANCE AND IMPACT OF THE STUDY: All selected factors showed impact on l
      asparaginase enzyme production by this isolated microbial strain either at the
      individual or interactive level. Incubation temperature, inoculum concentration,
      pH of the medium and nutritional source (glucose and ammonium chloride) had
      impact at individual level, while aeration, agitation and incubation time showed
      influence at interactive level. Significant improvement (ninefold increase) in
      enzyme production by this microbial isolate was noted under optimized
      environment.

PMID- 17448174
TI  - Sequence-based screening for self-sufficient P450 monooxygenase from a metagenome
      library.
AB  - AIMS: Cytochrome P450 monooxygenases (CYPs) are useful catalysts for oxidation
      reactions. Self-sufficient CYPs harbour a reductive domain covalently connected
      to a P450 domain and are known for their robust catalytic activity with great
      potential as biocatalysts. In an effort to expand genetic sources of self
      sufficient CYPs, we devised a sequence-based screening system to identify them in
      a soil metagenome. METHODS AND RESULTS: We constructed a soil metagenome library
      and performed sequence-based screening for self-sufficient CYP genes. A new CYP
      gene, syk181, was identified from the metagenome library. Phylogenetic analysis
      revealed that SYK181 formed a distinct phylogenic line with 46% amino-acid
      sequence identity to CYP102A1 which has been extensively studied as a fatty acid
      hydroxylase. The heterologously expressed SYK181 showed significant hydroxylase
      activity towards naphthalene and phenanthrene as well as towards fatty acids.
      CONCLUSIONS: Sequence-based screening of metagenome libraries is expected to be a
      useful approach for searching self-sufficient CYP genes. The translated product
      of syk181 shows self-sufficient hydroxylase activity towards fatty acids and
      aromatic compounds. SIGNIFICANCE AND IMPACT OF THE STUDY: SYK181 is the first
      self-sufficient CYP obtained directly from a metagenome library. The genetic and
      biochemical information on SYK181 are expected to be helpful for engineering self
      sufficient CYPs with broader catalytic activities towards various substrates,
      which would be useful for bioconversion of natural products and biodegradation of
      organic chemicals.

PMID- 17448175
TI  - Characterization of two ammonia-oxidizing bacteria isolated from reactors
      operated with low dissolved oxygen concentrations.
AB  - AIMS: To obtain ammonia-oxidizing bacterial (AOB) strains inhabiting low
      dissolved oxygen (DO) environments and to characterize them to better understand
      their function and ecology. METHODS AND RESULTS: Using a serial dilution method,
      two AOB strains (ML1 and NL7) were isolated from chemostat reactors operated with
      low DO concentrations (0.12-0.24 mg l(-1)). Phylogenetically, strains ML1 and NL7
      are affiliated to AOB within the Nitrosomonas europaea and Nitrosomonas
      oligotropha lineages, respectively. Kinetically, strain ML1 had high affinity for
      oxygen (0.24 +/- 0.13 mg l(-1)) and low affinity for ammonia (1.62 +/- 0.97 mg N
      l(-1)), while strain NL7 had high affinity for ammonia (0.48 +/- 0.35 mg l(-1)),
      but a surprisingly low affinity for oxygen (1.22 +/- 0.43 mg l(-1)). A co-culture
      experiment was used to iteratively estimate decay constants for both strains.
      CONCLUSIONS: The results indicated that AOB without high affinity for oxygen may
      have other mechanisms to persist in low DO environments, with high affinity for
      ammonia being important. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      provides a method to determine AOB growth kinetic parameters without assuming or
      neglecting decay constant. And, this is the first report on oxygen affinity
      constant of a N. oligotropha strain.

PMID- 17448176
TI  - Phosphate enrichment and fed-batch operation for prolonged beta-lactamase
      production by Bacillus licheniformis.
AB  - AIMS: Investigation of the phosphate effect and feeding strategy, i.e. linear and
      exponential feeding, to improve beta-lactamase production by Bacillus
      licheniformis considering the viability of the cells. METHODS AND RESULTS: Effect
      of phosphate enrichment on beta-lactamase production was investigated and
      resulted in 1.2-fold increase in beta-lactamase activity. Thereafter, exponential
      and linear feed profiles were established, after an initial batch phase for t = 0
      7.5 h. The highest beta-lactamase activity was obtained at fed-batch operation
      with exponential feeding (FBO1) condition as A = 106 U cm(-3), which is c. 1.7
      fold higher than that of the phosphate-enriched batch operation (PE-BO).
      CONCLUSIONS: Biphasic variations in beta-lactamase production was enhanced to
      monophasic variation with the exponential feeding strategy where the activity was
      obtained as A = 106 U cm(-3) at t = 16 h. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Phosphate enrichment decreases the intracellular ammonium concentration and
      organic acid excretion, but increrases beta-lactamase production. When batch
      operation (BO) and PE-BO are compared, it is seen that succinic acid formation
      decreased with the phosphate enrichment as a result of smooth operation of the
      tricarboxylic acid cycle. At FBO1 despite the increased lactic and acetic acid
      formation, beta-lactamase production increased 1.7-fold, and 92% of the cells
      were alive at the end of the fermentation.

PMID- 17448177
TI  - Mode of Salmonella and Escherichia coli O157:H7 inactivation by a stabilized
      oxychloro-based sanitizer.
AB  - AIM: To determine the mechanisms by which a stabilized oxychloro (SOC)-based
      sanitizer, applied to decontaminate seeds destined for sprout production,
      inactivates Escherichia coli O157:H7 ph1 and Salmonella serotype Meleagridis.
      MATERIALS AND RESULTS: The action of SOC on the metabolism, membrane and DNA
      integrity of Salmonella and E. coli O157:H7 was studied. In both pathogens, there
      was an oxidative burst and depletion of intracellular glutathione (GSH) upon
      initial exposure to 200 ppm SOC. Metabolic activity, measured via
      bioluminescence, decreased over a 4-h period in E. coli O157:H7 ph1 cells exposed
      to SOC. Membrane integrity, assessed through viability staining, decreased
      progressively over 23 h when exposed to SOC. The appearance of auxotrophic
      mutants suggested that DNA damage had also occurred. Enzymes rich in disulfide
      bonds (alkaline phosphatase and protease) were sensitive to the chlorite-based
      sanitizer. Through challenging other microbial types, it was found that Gram
      positive had higher tolerance to SOC than Gram negatives with the exception of
      Salmonella. MS2 bacteriophage was highly sensitive; however, Bacillus endospores
      were not inactivated by SOC. CONCLUSIONS: SOC inactivates E. coli O157:H7 and
      Salmonella through GSH oxidation and disruption of disulfide bonds. Ultimately,
      membrane damage resulting from prolonged exposure to SOC leads to the loss of
      cell viability. SIGNIFICANCE AND IMPACT OF THE STUDY: The results provide a basis
      for understanding why extended treatment times are required to inactivate
      bacteria using SOC.

PMID- 17448178
TI  - Potentials and pitfalls in analytical headache epidemiological studies--lessons
      to be learned from the Head-HUNT study.
AB  - The number of epidemiological headache studies is rapidly increasing, and has
      accentuated the need to improve the quality of the way studies are performed and
      how results are interpreted. The aims of this review were to summarize the main
      findings from the Head-HUNT study, to describe strengths and limitations of the
      Head-HUNT approach and to discuss the significance of some of our findings. Head
      HUNT included a large sample size of 51,383 participants that gave the
      opportunity to make analyses also of relatively rare conditions. The wide range
      of health-related information made it possible to adjust for many potential
      confounding variables. Blood samples for future genetic headache studies are
      available for a non-selected large group of individuals. The data show that among
      several factors that have been evaluated, age and gender were the two most
      clearly related to migraine, whereas analgesic overuse and the presence of some
      comorbid conditions were most strongly associated with the prevalence of chronic
      headache. Interesting relationships to blood pressure and thyroid-stimulating
      hormone levels were also found. Methodological problems in headache
      epidemiological studies are discussed and, in particular, problems with causal
      inferences. Despite the limitations of the head-HUNT study, we believe that the
      results so far have provided clues to causes and preventive factors of headache
      that should be explored in other populations and in prospective studies.

PMID- 17448179
TI  - Rizatriptan for the acute treatment of ICHD-II proposed menstrual migraine: two
      prospective, randomized, placebo-controlled, double-blind studies.
AB  - These are the first prospective studies to use criteria for menstrual migraine
      proposed in the 2004 revision of the International Classification of Headache
      Disorders (ICHD-II) to examine the efficacy of rizatriptan for treatment of a
      menstrual attack. Two identical protocols (MM1 and MM2) were randomized,
      parallel, placebo-controlled, double-blind studies. Adult women with ICHD-II
      menstrual migraine were assigned to either rizatriptan 10-mg tablet or placebo in
      a 2 : 1 ratio. Patients treated a single menstrual migraine attack of moderate or
      severe pain intensity. The primary end-point was 2-h pain relief and the
      secondary end-point was 24-h sustained pain relief. A total of 707 patients (MM1
      357, MM2 350) treated a menstrual migraine attack. The percentage of patients
      reporting 2-h pain relief was significantly greater for rizatriptan than for
      placebo (MM1 70% vs. 53%, MM2 73% vs. 50%), as was the percentage of patients
      reporting 24-h sustained pain relief (MM1 46% vs. 33%; MM2 46% vs. 33%).
      Rizatriptan 10 mg was effective for the treatment of ICHD-II menstrual migraine,
      as measured by 2-h pain relief and 24-h sustained pain relief.

PMID- 17448180
TI  - Cannabinoid and vanilloid effects of R(+)-methanandamide in the hemisected
      meningeal preparation.
AB  - The endogenous cannabinoid R(+)-methanandamide (mAEA) exerts differential anti-
      and pronociceptive effects by activating both cannabinoid (CB1) and vanilloid
      (TRPV1) receptors of nociceptive primary afferents. The significance of these
      effects in meningeal nociception was evaluated by modulation of calcitonin gene
      related peptide (CGRP) release from meningeal afferents measured in an in vitro
      preparation of the hemisected rat skull. Temperature steps to 39 degrees C and 45
      degrees C caused heat-dependent increases in CGRP release. One micromolar mAEA
      inhibited CGRP release at 32 degrees C but facilitated it at 45 degrees C. This
      effect was abolished in the presence of the TRPV1 receptor antagonist
      capsazepine. Lower doses of mAEA had no effect on basal or heat-evoked release.
      In the presence of the CB1 receptor antagonist SR141716 (0.2 microm) heat
      stimulated increase in CGRP release was facilitated. CGRP release in the presence
      of SR141716 (0.2 microm) was further increased by adding mAEA at a concentration
      which had no effect on its own. These results confirm an opposing functional role
      for anandamide at CB1 and TRPV1 receptors on meningeal afferents.

PMID- 17448181
TI  - Migraine and adiponectin: is there a connection?
AB  - Migraine is a common disorder, characterized by recurrent episodes of headache
      and associated symptoms. The full pathophysiology of migraine is incompletely
      delineated. Current theories suggest that it is a neurovascular disorder
      involving cortical depression, neurogenic inflammation and vasodilation. Various
      neuropeptides and cytokines have been implicated in the pathophysiology of
      migraine including calcitonin gene-related peptide, interleukin (IL)-1, IL-6 and
      tumour necrosis factor (TNF)-alpha. There is evidence demonstrating an
      association between migraine and processes associated with inflammation,
      atherosclerosis, immunity and insulin sensitivity. Similarly, adiponectin, an
      adipocytokine secreted by adipose tissue, has protective roles against the
      development of insulin resistance, dyslipidaemia and atherosclerosis and exhibits
      anti-inflammatory properties. The anti-inflammatory activities of adiponectin
      include inhibition of IL-6 and TNF-induced IL-8 formation, as well as induction
      of the anti-inflammatory cytokines IL-10 and IL-1 receptor antagonist.
      Adiponectin levels are also inversely correlated with C-reactive protein (CRP),
      TNF-alpha and IL-6 levels. Likewise, recent studies have shown a possible
      correlation between CRP, TNF-alpha and IL-6 and migraine attacks. In addition,
      insulin sensitivity is impaired in migraine and obesity is a risk factor for the
      transformation from episodic to chronic migraine. In this review we discuss the
      basic science of adiponectin and its potential connection to the pathophysiology
      of migraine. Future research may focus on how adiponectin levels are potentially
      altered during migraine attacks, and how that information can be potentially
      translated into migraine therapy.

PMID- 17448182
TI  - Hot bath-related headache controlled by topiramate.

PMID- 17448184
TI  - Botulinum toxin in headache treatment: the end of the road?

PMID- 17448186
TI  - New appendix criteria open for a broader concept of chronic migraine.

PMID- 17448187
TI  - Do 5HT1B/1D receptor agonists have an effect on mood and anxiety disorders?

PMID- 17448189
TI  - Atypical nevi of the scalp in adolescents.
AB  - BACKGROUND: A few reports in the literature point out that in special areas of
      the body, nevi can have peculiar pseudomelanomatous features. In our routine
      work, we have met few examples of atypical nevi with peculiar features on the
      scalp of teenagers. To evaluate the frequency and the biological behaviour of
      these lesions, we have conducted a complete survey on melanocytic lesions on the
      scalp in a significant group of patients. MATERIALS AND METHODS: Thirty-nine nevi
      of the scalp were from adolescents (12-18 years), 160 from adults, and 30 from
      children below the age of 12 years. RESULTS: About 10% of the melanocytic nevi of
      the scalp of adolescents have atypical cytological and architectural aspects that
      are different from those seen in Clark's dysplastic nevus. The most striking
      features were the presence of large bizarrely shaped nests scattered disorderly
      along the junction with follicular involvement. Other findings were pagetoid
      spread of cells above the junction and the discohesive pattern of the melanocytes
      in the nests. Mild cytological atypia was present but less significant. Such
      distinctive aspects are not found in nevi of the same site in adults or younger
      children. The general pattern of these atypical nevi of the scalp of adolescents
      closely recalls that of the so-called atypical nevi on special sites, i.e. nevi
      on mammary line, genitalia and body's folds. Despite the architectural and
      cytological atypia, clinical follow-up does not show any tendency to recur or
      proclivity to malignant behaviour. CONCLUSIONS: Despite their similarities with
      melanoma, the nevi with atypical features of the scalp of adolescents are
      probably an entirely benign entity, at least at the moment of their excision.
      However, although benign, the relationship of this peculiar group of nevi with
      melanomas developed in adulthood remains entirely unknown, and the complete
      excision with conservative margins seems a recommendable procedure.

PMID- 17448190
TI  - Nestin expression in cutaneous melanomas and melanocytic nevi.
AB  - BACKGROUND: Nestin is one of the intermediate filaments that are expressed in
      proliferating neural progenitor cells during development of the central nervous
      system (CNS) and peripheral nervous system. Postnatal re-expression of the
      protein occurs mainly under pathological conditions, including injury and
      neoplasia. In this study, nestin expression was detected in both benign and
      malignant melanocytic skin lesions and its diagnostic relevance was then
      evaluated. METHODS: Altogether 139 bioptic tissue samples consisting of 42
      nodular melanomas, 32 superficial spreading melanomas, 12 metastatic melanomas,
      10 dysplastic nevi and 43 common melanocytic intradermal and dermoepidermal nevi
      were analysed using indirect immunohistochemical staining. RESULTS: We
      demonstrated that nestin immunostaining was significantly increased in melanomas
      where it correlated with more advanced stages of the disease. CONCLUSION: We
      conclude that expression of the intermediate filament protein nestin might be an
      indicator of tumor dedifferentiation and more aggressive behaviour. Furthermore,
      we suggest that nestin might be a relevant marker of tumorous and non-tumorous
      angiogenesis.

PMID- 17448191
TI  - Displacement of dermal solar elastosis in malignant melanoma.
AB  - BACKGROUND: Ultraviolet radiation (UVR) is a major environmental causal factor
      for skin malignancy. In this study, we investigated the morphology of the solar
      elastosis (SE) band in benign and malignant melanocytic lesions. METHODS: We
      measured the SE band in perilesional and lesional skin of 13 melanomas (9
      invasive and 4 in situ) and 11 melanocytic nevi (5 usual intradermal nevi, 4 blue
      nevi and 2 desmoplastic nevi) occurring in sun-exposed areas. RESULTS: The
      melanoma and nevus groups had similar age range, gender ratio and anatomic
      distribution. The mean SE thickness was 0.35 mm in melanomas and 0.29 mm in nevi
      (p = 0.56), indicating similar UVR exposure. There was a mean downward SE
      displacement (SED) of 0.43 mm in melanomas and essentially no displacement (-0.02
      mm) in nevi (p < 0.005). Tumor cells and inflammatory host response were
      responsible for SED in melanoma. CONCLUSIONS: SED may help in the differential
      diagnosis of melanocytic lesions in sun-exposed areas. In melanoma, the new
      lesion depresses the pre-existing SE band. Conversely, the long-standing nevus co
      exists with the SE band without significant displacement. Evaluation of the SE
      band may help to differentiate melanoma with chronic sun-induced damage as they
      have a distinct set of molecular alterations.

PMID- 17448192
TI  - Renal cell carcinoma marker (RCC-Ma) is specific for cutaneous metastasis of
      renal cell carcinoma.
AB  - BACKGROUND: Renal cell carcinoma marker (RCC-Ma) is a monoclonal antibody against
      a normal renal proximal tubule antigen. RCC-Ma expression is relatively specific
      for primary clear cell renal cell carcinoma. Its expression in cutaneous
      metastasis of renal cell carcinoma (MRCC) and other cutaneous clear cell lesions
      has not been studied. METHODS: One hundred and thirty-seven cutaneous clear cell
      lesions including eight xanthomas, 32 xanthelasmas, 25 xanthogranulomas, seven
      balloon cell nevi, six clear cell hidradenomas, 29 sebaceous adenomas, six
      sebaceous epitheliomas, eight sebaceous carcinomas, and 16 MRCC were examined
      using immunohistochemistry for the expression of RCC-Ma. RESULTS: RCC-Ma was
      expressed in 10 of 16 (62.5%) MRCC, all with greater than 20% of cell labeling.
      Of these, 4 of 10 (40%) labeled with a membranous pattern and 6 of 10 (60%)
      labeled with both a membranous and a cytoplasmic pattern. RCC expression was not
      seen in any of the other clear cell lesions (p < 0.001). Furthermore, lack of
      expression in each of the other diagnostic groups was significant when each group
      was compared with the MRCCs (p < 0.01 at least for each group). CONCLUSIONS: Our
      study demonstrates that RCC may be a valuable component of a panel of
      immunohistochemical markers when evaluating cutaneous clear cell lesions.

PMID- 17448193
TI  - Telomerase expression in sebaceous lesions of the skin.
AB  - BACKGROUND: Recent studies have demonstrated telomerase expression in
      ophthalmologic sebaceous carcinoma and have suggested possible diagnostic utility
      in distinguishing these neoplasms from sebaceous adenomas. The aim of this study
      was to evaluate telomerase expression via human telomerase reverse transcriptase
      (hTERT) immunohistochemical staining in a spectrum of sebaceous lesions of the
      skin. METHODS: Paraffin-embedded sections from sebaceous hyperplasia (11), nevus
      sebaceus (22), sebaceous adenoma (19), sebaceoma (11), and sebaceous carcinoma
      (14) were evaluated for intensity (0 to 3+) and pattern of anti-hTERT staining.
      RESULTS: Strong (2 to 3+) hTERT staining was observed in nucleoli of germinative
      cells and immature sebocytes in all sebaceous lesions, whereas mature sebocytes
      were negative. The distribution pattern paralleled features seen by routine
      haematoxylin and eosin-stained sections. CONCLUSIONS: All hyperplastic and
      neoplastic sebaceous skin lesions expressed hTERT in this immunohistochemical
      study. The pattern of staining was predictive of the histologic pattern of the
      process but does not significantly add to our diagnostic armamentarium of
      sebaceous lesions.

PMID- 17448194
TI  - Histological and immunohistochemical study of granuloma annulare and subcutaneous
      granuloma annulare in children.
AB  - BACKGROUND: The aim of this study was to investigate the histological and
      immunohistochemical features of granuloma annulare (GA) in comparison to deep
      granuloma annulare (DGA) and granulomatous dermatoses (GDs). METHODS: Our
      material comprised 13 GA, 8 DGA and 1 atypical granuloma annulare (AGA) in a
      child with primary immunodeficiency, 10 cases of nonspecific GDs and 1 case of
      sarcoidosis with cutaneous involvement. The immunohistochemical streptavidin
      biotin-Horseradish peroxidase (HRP) analysis was performed on paraffin sections
      for the detection of CD68/KP-1, CD68/anti-human CD68 clone PGM1 (PGM1), lysozyme,
      S-100 protein, CD1a, CD3, CD20/L-26, CD4 and CD8. RESULTS: All 13 GA were
      characterized by typical palisading and interstitial granulomas. In 6 cases, the
      lesion extended to the subcutaneous fat, while a considerable perivascular
      lymphocytic infiltrate without any signs of vasculitis was observed in 10 cases.
      The DGA were located to the deep dermis and subcutaneous fat, showing palisading
      granulomas with central necrobiosis. Immunohistochemistry revealed a broad
      intense expression of CD68/PGM1 in the histiocytic population in all cases, a
      constant but fainter detection of CD68/KP-1 and a variable one of lysozyme. T
      cell markers (CD3, CD4 and CD8) were mainly detected in the perivascular
      lymphocytic infiltrate of GA and DGA, with CD4+ T lymphocytes predominating over
      CD8+ in GA and DGA, while CD8+ T lymphocytes was the predominant population in
      AGA. CONCLUSIONS: CD68/PGM1 is a sensitive and reliable histiocytic marker in
      confirming the histiocytic nature of equivocal GA and DGA, but the histiocytic
      immunoprofile is of no particular usefulness in differentiating GA from other GD.

PMID- 17448195
TI  - Cutaneous clear-cell granular cell tumors: the histologic description of an
      unusual variant.
AB  - BACKGROUND: Granular cell tumors (GCTs) are neoplasms showing nerve sheath
      differentiation that can arise in the skin but, to our knowledge, have not been
      associated with significant clear-cell morphology. METHODS: Two patients
      developed four separate GCTs with distinctive, diffuse clear-cell change, which
      completely camouflaged the primary differentiation. The morphology,
      histochemistry and immunohistochemistry of the lesions are described and are
      compared with the presence and extent of clear-cell change in 14 other cases of
      GCTs. RESULTS: The index cases were relatively broad proliferations with uniform
      diffuse clear-cell change and only minimal overlying epidermal hyperplasia.
      Prominent lymphoid nodules were present at the periphery. These clear-cell
      granular tumors were positive for S-100 protein, p75, CD68, NKI/C3 and neuron
      specific enolase and were negative for epithelial mucin, periodic acid-Schiff,
      carcinoembryonic antigen, HMB-45, Melan-A, smooth muscle actin, Leu7,
      synaptophysin, CD34, factor XIIIa, epithelial membrane antigen and cytokeratin.
      Three of the fourteen comparison cases were found to have no clear-cell change,
      eight showed focal clear-cell change and three showed moderate clear-cell change.
      CONCLUSIONS: The distinctive morphology and the immunohistochemical results are
      discussed in the context of the differential diagnosis of clear-cell cutaneous
      tumors.

PMID- 17448197
TI  - Primary cutaneous neuroendocrine cell carcinoma (Merkel cell carcinoma) with
      prominent microcystic features, mimicking eccrine carcinoma.
AB  - Although primary cutaneous neuroendocrine cell carcinoma [Merkel cell carcinoma
      (MCC)] may show divergent features, including microcystic ('tubuloglandular'),
      squamous, eccrine and rhabdomyoblastic, a diffuse microcystic pattern is
      exceedingly rare. In this study, we present two cases of MCC with prominent
      microcystic features, which precluded a definitive diagnosis in the initial punch
      biopsy. Both patients were middle-aged men with a history of rapidly growing
      plaques of the back or posterior neck. Punch biopsies from both patients revealed
      an infiltrating neoplasm with prominent microcystic features that mimick
      tubuloglandular structures, lined by hyperchromatic basaloid cells, which were
      strongly positive for chromogranin and BerEP4, variably positive for CK7 and
      CK5/6 and negative for CK20, synaptophysin, S-100, epithelial membrane antigen
      (EMA), gross cystic disease fluid protein-15 (GCDFP-15), estrogen/progesterone
      receptors (ER/PR), thyroid transcription factor 1 (TTF1) and carcinoembryonic
      antigen (CEA). The re-excision specimens showed a multifocal intra-epidermal
      component in one case and typical finely stippled nuclear chromatin in both
      cases. Although the lack of CK20 staining is unusual, the histologic
      characteristics along with the remaining immunohistochemical studies favor the
      diagnosis of a primary cutaneous neuroendocrine cell carcinoma over the variants
      of eccrine carcinoma or basal cell carcinoma with neuroendocrine differentiation.
      Our cases illustrate that prominent microcystic features, mimicking glandular
      differentiation, may occur in MCC and pose a diagnostic challenge in small biopsy
      specimens.

PMID- 17448196
TI  - Pustulo-ovoid bodies of Milian in granular cell tumors.
AB  - BACKGROUND: Granular cell tumors (GCTs) are benign neural tumors with a distinct
      histologic appearance on light microscopy, characterized by eosinophilic
      cytoplasmic granules. Pustulo-ovoid bodies of Milian (POB) are larger granules
      surrounded by a clear halo. There have been no histologic studies to document
      their prevalence in GCT. METHODS: We examined the sections of 47 cases of GCT
      stained with hematoxylin and eosin to determine the frequency of POB within this
      tumor. POB were measured per 10 high-power fields (HPFs) and were divided into
      the following categories: less than 10 POB per 10 HPFs, 10-30 per 10 HPFs, 30-50
      per 10 HPFs and greater than 50 per 10 HPFs. RESULTS: POB were present in 100% of
      the specimens examined. Eleven cases (23%) had between 1 and 9 POBs per 10 HPFs,
      twelve cases (26%) had between 10 and 29 POBs per HPFs, five cases (11%) had
      between 30 and 50 POBs per HPFs and nineteen cases (40%) had greater than 50 POBs
      per HPFs. When grouped according to clinical characteristics, there was an even
      distribution of POB by age, sex and site of the tumor. CONCLUSIONS: In our
      series, POB were present in varying numbers in all the tumors studied. They
      appear to represent the heterogeneity of the lysosomes, giving the appearance of
      large granules that have partially detached from the adjacent cytoplasm. POB are
      an easily recognizable component of GCTs.

PMID- 17448198
TI  - Immunohistochemical staining of CD10 in atypical fibroxanthomas.
AB  - BACKGROUND: The histologic diagnosis of atypical fibroxanthoma (AFX) may be
      difficult at times with a differential diagnosis including spindle
      cell/desmoplastic melanoma and a poorly differentiated squamous cell carcinoma
      (SCC). While there are immunohistochemical stains that may be used to support a
      diagnosis of either melanoma or carcinoma, the diagnosis of AFX tends to be one
      of exclusion. METHODS: A total of 35 cases including 16 AFXs, 10 poorly
      differentiated SCCs and nine spindle cell/desmoplastic melanomas were stained
      with the antibody against CD10. RESULTS: There was strong (3+) diffuse expression
      of CD10 in 15/16 (94%) AFXs, weak (1+) to moderate (2+) patchy expression of CD10
      in 5/10 (50%) SCCs and weak (1+) expression of CD10 in 3/9 (33%) spindle
      cell/desmoplastic melanomas. CONCLUSION: CD10 expression is helpful in
      distinguishing between AFXs, carcinomas and melanomas and will be useful in a
      panel of antibodies when distinguishing between these entities.

PMID- 17448199
TI  - Melanoma associated with a dermatofibroma.
AB  - BACKGROUND: Dermatofibromas are common benign cutaneous fibrohistiocytic
      neoplasms, whereas melanomas are potentially aggressive malignancies.
      Differentiating these two entities can occasionally be difficult. METHODS: We
      report the case of a 56-year-old female presenting with a firm pink papule on the
      left thigh. RESULTS: Histopathology revealed atypical melanocytes in the
      epidermis and papillary dermis with numerous mitotic figures and intraepidermal
      pagetoid spread. Within the dermis was a poorly demarcated collection of
      epithelioid and spindled cells with intermixed keloidal collagen. The atypical
      melanocytes stained for MART-1 and S-100, whereas the underlying fibrohistiocytic
      tumor took up factor XIIIa immunostain, confirming the diagnosis of invasive
      malignant melanoma occurring in association with a dermatofibroma. CONCLUSIONS:
      This case emphasizes the role of immunohistochemical stains in correctly
      diagnosing melanocytic and histiocytic neoplasms.

PMID- 17448200
TI  - Aggressive osteogenic desmoplastic melanoma: a case report.
AB  - A case of an osteogenic desmoplastic melanoma occurring on the sole of the foot
      of a 60-year-old African American man is described. The tumor measured 4.8 cm in
      greatest dimension, invaded to a thickness of 2.2 cm and metastasized to four of
      ten inguinal lymph nodes. The majority of the tumor had a classic desmoplastic
      phenotype with malignant spindle cells set in a sclerotic and myxoid matrix and
      foci of lymphocyte aggregation. In other areas, there were thick trabeculae of
      bone rimmed by malignant epithelioid melanocytes. There was a markedly atypical
      lentiginous hyperplasia in the overlying epidermis. Imaging showed no continuity
      with the underlying calcaneus. The tumor was characterized immunohistochemically
      by S100 positivity. Pathologists should be aware of this diagnosis and should
      differentiate it from osteosarcoma.

PMID- 17448201
TI  - Primary chondroid melanoma of the nasal skin: a rare melanoma variant at a
      previously undocumented site.
AB  - Heterologous differentiation is exceedingly rare in melanoma. Only four cases of
      melanoma demonstrating exclusive cartilaginous differentiation have been
      documented, all having occurred on the lower extremity. We report a chondroid
      melanoma involving the nasal skin and presenting clinically as a basal cell
      carcinoma. Both Melan-A and microphthalmia transcription factor protein
      immunoperoxidase stains were positive in our case, demonstrating the potential
      utility of these two stains in chondroid melanoma. We also provide a succinct
      review of the literature on this rare melanoma variant.

PMID- 17448202
TI  - Pseudomycetoma caused by Microsporum canis in an immunosuppressed patient: a case
      report and review of the literature.
AB  - BACKGROUND: A 65-year-old woman with a history of liver and kidney
      transplantation presented with a pruritic and tender rash of 2-year duration on
      her left knee. METHODS: The patient had a physical examination, and multiple skin
      biopsies were performed. RESULTS: Examination showed a cluster of dome-shaped,
      violaceous papules. A skin biopsy specimen showed multiple granules containing
      basophilic material within the superficial to mid dermis. The grains were
      embedded in an eosinophilic substance and surrounded by granulomatous
      inflammation. A Gomori methenamine silver stain showed abundant septate hyphae,
      and cultures grew colonies of Microsporum canis. A diagnosis of dermatophytic
      granuloma, or pseudomycetoma, was made. After considering the patient's immune
      status, a prolonged course of fluconazole was initiated. CONCLUSION: Microsporum
      canis, a frequently encountered zoophilic dermatophyte associated with tinea
      capitis and tinea corporis, is rarely associated with a mycetoma-like
      presentation, grain formation, or systemic infection. The medical literature
      describes only six cases of M. canis causing mycetoma-like formations in
      immunocompromised and immunocompetent patients. This case report describes an
      unusual presentation of a common dermatophyte infection, and the literature
      review summarizes the importance of recognizing atypical presentations of
      dermatophyte infections. Such infections may warrant more aggressive treatment in
      immunocompromised patients.

PMID- 17448203
TI  - Atypical neurothekeoma: a new case and review of the literature.
AB  - BACKGROUND: Neurothekeoma is a rare neoplasm ascribed into the broad category of
      benign peripheral nerve sheath tumors. The atypical cellular variant of this
      neoplasm, showing a peculiar histological pattern, has been very rarely reported
      in literature. METHODS: The clinical, histopathological and immunohistochemical
      profile of a new case of atypical cellular neurothekeoma in a 32-year-old woman
      is reported. RESULTS: The described neoplasm showed the histological features of
      atypical variant of cellular neurothekeoma with high-rate mitotic activity and
      deep penetration into subcutaneous fat. CONCLUSIONS: Because only few cases of
      atypical neurothekeoma have been reported in literature, clinical and
      morphological available data on this neoplasm are very few, and its prognosis
      remains uncertain; anyway, dermatologists should be aware of histological
      features of this neoplasm for which a complete surgical excision is recommended.

PMID- 17448205
TI  - The emerging role of botulinum toxin in the treatment of temporomandibular
      disorders.
AB  - The objective of this review was to discuss the emerging role of botulinum toxin
      in the treatment of temporomandibular disorders (TMD), to review the current
      literature, recent clinical trials, as well as preliminary data from our own
      clinical study, and to formulate an algorithm for the work-up and treatment of
      TMD.

PMID- 17448206
TI  - Craniofacial osseointegration.
AB  - In year 2007, 30 years have elapsed since the first patient was supplied with a
      craniofacial osseointegrated implant. The reason for implanting in this patient
      was a severe conductive hearing loss, which necessitated the use of a bone
      conduction hearing aid. By utilizing the possibility to transmit sound to the
      cochlea via direct bone conduction, a new era in audiology was established.
      Further applications of osseointegration in the craniofacial field is related to
      the rehabilitation of patients with defects from cancer therapy, malformations,
      traumatic amputations and burns. Specific fields of osseointegration in this
      respect are due to possible side effects from radiotherapy and chemotherapy that
      will affect osseointegration negatively. Other aspects are related to
      osseointegration in children. This review will focus on the knowledge gained
      during the first 30 years of craniofacial osseointegration.

PMID- 17448207
TI  - Orofacial lesions in treated southeast Brazilian leprosy patients: a cross
      sectional study.
AB  - AIM: The aim of the present study was to clinically evaluate the oral mucosa
      lesions of leprosy patients during and after multi-drug therapy. METHODS:
      Clinical examination, medical and dental history examination was performed in 100
      leprosy patients. RESULTS: The results revealed that 71 patients, 50 men and 21
      women, exibited oral lesions. The most frequent lesions were: fissured tongue (18
      cases), inflammatory papillary hyperplasia (16 cases), chronic atrophic
      candidiasis (10 cases), fibroma (10 cases), erythematous candidiasis (eight
      cases), and traumatic ulceration (seven cases). CONCLUSION: We conclude that
      leprosy-related lesions are not present in patients undergoing treatment for
      leprosy, probably due to response to multidrug therapy.

PMID- 17448208
TI  - Immunoprofile of focal lymphocytic infiltration in minor salivary glands of
      healthy individuals.
AB  - AIM: To characterize the immunohistochemical profile of the inflammatory cells
      included in the focal lymphocytic infiltration in the minor salivary glands of
      healthy individuals. MATERIALS AND METHODS: Tissue samples of the labial and
      palatal salivary glands from 46 postmortem subjects, demonstrating the presence
      of focal lymphocytic infiltration were quantitatively evaluated for the presence
      of T- and B-cell lymphocytes, plasma cells and macrophages by immunohistochemical
      and morphometric methods. RESULTS: B-cell lymphocytes, the predominant cell
      population in labial (67.5%) and palatal salivary glands (60.8%), were more
      frequent than T-cell lymphocytes in both glands (P < 0.001). Among the T-cell
      lymphocytes, CD(4)-positive cells were significantly more prevalent than the
      CD(8)-positive cells (P < 0.001). Plasma cells were almost absent, comprising
      only 0.01% of the focal lymphocytic infiltration cells of the labial and palatal
      salivary glands. CONCLUSIONS: Focal lymphocytic infiltration in the samples of
      the salivary glands obtained from healthy individuals is devoid of plasma cells.
      This can serve as an additional means to differentiate between focal lymphocytic
      infiltration in patients with Sjogren's syndrome, in which plasma cells are
      abundant, and focal lymphocytic infiltration in individuals with other causes of
      focal sialadenitis.

PMID- 17448209
TI  - Candida albicans does not invade carious human dentine.
AB  - AIM: Candida albicans has been proposed to be a caries pathogen, but the evidence
      for its specific role is lacking. To be considered significant in caries
      progression, a marked amount of yeasts should be present in a lesion. The aim of
      the study was to investigate the presence of C. albicans in dentinal caries
      lesions. MATERIALS AND METHODS: To demonstrate the extension of caries and to
      identify the bacteria in a lesion, sections of 10 carious human teeth were
      stained with Gram and Giemsa stains. C. albicans was detected with periodic acid
      Schiff (PAS) staining and by immunohistochemistry using a C. albicans-specific
      antibody 3H8. Thirty sections were used for each staining (in total 120
      sections). RESULTS: Extensive bacterial invasion and intensive staining by PAS
      occurred in all samples. However, with the C. albicans-specific antibody, only 30
      (3.3%) sections stained weakly positive, with a few stained cells on the lesion
      surface. However, the positive identification of C. albicans, based on the
      morphology of the cells, was not possible. CONCLUSIONS: The results do not
      support the previous suggestion that C. albicans is important in the dentine
      caries pathology. In addition, because of its unspecific nature, PAS turned out
      to be an unsuitable method for detecting yeasts in carious tooth samples.

PMID- 17448210
TI  - Pharmacodiagnostic evaluation of EGFR expression in oral squamous cell carcinoma.
AB  - OBJECTIVE: To determine epidermal growth factor receptor (EGFR) expression in
      oral squamous cell carcinomas (OSCC), and its possible relationships with
      clinical findings, histological findings, disease course and prognosis. MATERIALS
      AND METHODS: Surgical specimens of 47 OSCCs were studied immunohistochemically
      for detection of EGFR using a standardized immunohistochemical detection system
      (EGFR PharmaDx kit). Statistical analysis was used to investigate possible
      relationships between EGFR expression and clinical findings, histological
      findings, cell proliferation (MIB1 labelling index), disease course and patient
      survival. RESULTS: Epidermal growth factor receptor expression was absent or weak
      in 12 cases (25.5%) and moderate or intense in 35 cases (74.5%). However, EGFR
      expression did not show statistically significant associations with any of the
      clinical, histological, biological or prognostic variables considered.
      CONCLUSION: First, despite previous suggestions that EGFR is a useful indicator
      of biological tumour behaviour, the present results suggest that EGFR is not a
      useful indicator of prognosis in OSCC. Secondly, the high prevalence of EGFR
      overexpression suggests that the possibility of anti-EGFR therapy in OSCC merits
      further investigation.

PMID- 17448211
TI  - Fanconi's anemia: clinical and radiographic oral manifestations.
AB  - BACKGROUND: Fanconi's anemia (FA) is a rare autosomal recessive disorder
      characterized by progressive bone marrow failure, congenital abnormalities, and
      predisposition to malignancies. There are 11 genetic subtypes characterized by
      complementation groups - FA- A, B, C, D1, D2, E, F, G, I, J, and L. OBJECTIVE: To
      evaluate and describe clinical, oral and radiographic manifestations of patients
      with FA. METHODS: A quantitative analysis of clinical manifestations, oral
      lesions and panoramic radiographs was performed in 33 patients. RESULTS: Clinical
      manifestations included melanin skin pigmentation, skin vascular and ocular
      anomalies. Melanin pigmentation on oral mucosa, traumatic lesions, gingival
      bleeding, dental biofilm and gingival alterations were the main oral
      manifestations that were found. Oral and clinical manifestations were not
      dependent on patient's sex. No significant statistical difference between females
      and males was detected. Dental anomalies were not remarkable either at clinical
      or at radiographic examinations. Although several dental anomalies were observed
      in patients with FA, the correlation between this disease was not established
      from this study. Panoramic radiographs showed agenesis, taurodontism, radicular
      anomalies such as dilaceration, tapering, and foreshortening. CONCLUSION: This
      study suggests that gingival alterations are associated with defective oral
      hygiene but not with hematologic conditions. It also helps elucidate oral
      manifestations of FA. These patients are living longer and need special dental
      care.

PMID- 17448212
TI  - An in vitro study of the effect of some dietary components on calculus formation:
      regulation of calcium phosphate precipitation.
AB  - OBJECTIVE: We studied the effects of food components on the in vitro formation of
      calcium phosphate precipitates. MATERIALS AND METHODS: The effects of food
      components, such as starch, soybean flour, fish meal, rapeseed oil, and coconut
      oil, on calcium phosphate precipitation were studied using a pH drop method.
      RESULTS: Although the addition of starch had no effect on the rate of
      precipitation of amorphous calcium phosphate (ACP), it increased both the rate of
      transformation of ACP to hydroxyapatite (HAP) and the induction time (i.e. time
      for the initiation of transformation of ACP to HAP to occur); this was
      irrespective of the heat treatment of the starch. Amylopectin (insoluble
      constituent of starch) was effective in increasing the rate of HAP
      transformation, but amylose (soluble constituent of starch) was not. Oil specimen
      obtained from rapeseed (400 microl ml(-1)) increased the entire reaction of
      calcium phosphate precipitation, but that from coconut did not. Protein food,
      such as soybean flour and fish meal, decreased the rate of transformation of ACP
      to HAP and increased the induction time, while they had no effect on the rate of
      ACP precipitation. CONCLUSION: These results suggest that carbohydrate and oil
      (both are staple diets for the humans) enhance oral calcification (dental
      calculus formation or re-mineralization of tooth enamel), while side dishes of
      protein food would decrease it.

PMID- 17448213
TI  - Ameloblastomas: a regional Latin-American multicentric study.
AB  - AIM: To classify 163 ameloblastoma cases according to the new WHO Classification
      of Odontogenic Tumours (2005) and analyse their clinical and microscopic
      features. METHODS: We studied the clinico-pathological features of 163
      ameloblastoma cases from nine regional Latin-American institutions from Mexico
      and Guatemala. RESULTS: Ameloblastomas comprised 22.7% of all odontogenic
      tumours. The mean age was 41.4 years for solid ameloblastoma (SA) and 26.3 years
      for unicystic ameloblastoma (UA) (P < 0.001) and both sexes were almost equally
      affected. The mandible was mainly affected for both UA and SA. The mean size was
      6.2 cm for SA and 6.3 cm for UA cases. The recurrence rate was 21.7% for SA and
      12.6% for UA. UA was twice as more frequent than the solid variant. CONCLUSIONS:
      In this study we found that UA was frequently misdiagnosed as SA; however, there
      are enough clinical and microscopic features that allow for an accurate
      differentiation between both types of ameloblastoma that should be recognized for
      surgical and prognostic purposes. In this study, SA was not found in patients
      younger than 20 years, UA had a constant myxoid stroma while mature connective
      tissue was more frequently associated with the solid type.

PMID- 17448214
TI  - Interleukin-1 receptor antagonist gene polymorphism and gingivitis in children.
AB  - AIM: To investigate the role of the polymorphism of a variable numbers of tandem
      repeats of interleukin-1 receptor antagonist gene (IL-1RN) on gingivitis in
      children. MATERIALS AND METHODS: A total of 146 Caucasian subjects (98 subjects
      with gingivitis and 48 controls) aged 8-12 years, were enrolled. Plaque and
      Calculus Indices were recorded to assess the oral hygiene. Gingival and Bleeding
      on Probing Indices were used to identify patients with gingivitis. DNA was
      extracted from epithelial cells of the cheek. Normal polymerase chain reaction
      was used for IL-1Ra genotyping. RESULTS: A significant association was observed
      between IL-1Ra gene polymorphism and gingivitis in children (P = 0.008). The IL
      1RN*2 allele (A2) was significantly more frequent in controls (37%vs 22% in
      children with gingivitis). In addition, the carriage of A2 seemed to be
      protective against gingivitis, and it was more frequent in controls (60%vs 40% in
      children with gingivitis, P = 0.008). Moreover, multiple logistic regression
      analysis showed that the association between IL-1Ra gene polymorphism and
      gingivitis in children remained significant (P = 0.014) regardless of the
      significant influence of plaque (P = 0.013). CONCLUSION: IL-1Ra gene
      polymorphisms could have an active role in the pathogenesis of gingivitis in
      Caucasian children and IL-1RN*2 allele could be a protective marker against
      gingivitis.

PMID- 17448215
TI  - The effect of cortical activation on orthodontic tooth movement.
AB  - OBJECTIVE: Cortical activation is one of the procedures to accelerate tooth
      movement by manipulating the cortical bone. In this study, the effect of cortical
      activation on orthodontic tooth movement was investigated clinically and
      histologically in the surrounding bony tissue. MATERIALS AND METHODS: In the
      lower and upper jaws of two beagle dogs, cortical activation was applied to the
      buccal and lingual side of the alveolar bone in the right jaw where 12 holes were
      made on each cortical plate 4 weeks after the extraction of all the second
      bicuspids while under deep anesthesia. All third bicuspids on both jaws were
      forced to move forward by a 150-g force using NiTi coil spring with/without
      guiding wire. The tooth movement was measured and the animals were killed after
      tooth movement. RESULTS: Rapid initial tooth movement was apparent after cortical
      activation. However, after 6 months of cortical activation, the cell number and
      cellular activity of the surrounding periodontal tissue were decreased.
      CONCLUSIONS: This experiment showed that rapid initial tooth movement was
      apparent following the application of orthodontic force after cortical activation
      but the cellular activity and fibroblast structure were abnormal in the
      surrounding periodontal tissue.

PMID- 17448216
TI  - Stimulated whole salivary flow rate and composition in menopausal women with oral
      dryness feeling.
AB  - The aim of this study was to compare stimulated whole saliva flow rate and
      composition of menopausal women with/without oral dryness (OD) feeling. A case
      control study was carried out in 42 selected menopausal women aged 52-73 years
      with or without OD feeling (21 as case and 21 as control) conducted at the Clinic
      of Oral Medicine, Tehran University of Medical Sciences. Paraffin-stimulated
      saliva samples were obtained by expectoration. The stimulated whole saliva
      composition was measured by a spectrophotometer [magnesium (Mg(+2)), calcium
      (Ca(+2)), chloride (Cl(-)), inorganic phosphate (Pi) and total protein], flame
      photometry [sodium (Na(+))] and ion selective electrode (ISE) [potassium (K(+))]
      methods. No significant differences were found in stimulated whole saliva flow
      rate, Mg(+2), Cl(-), Pi, Na(+), K(+) and total protein concentrations between the
      two groups, but the mean calcium concentration was significantly higher in cases
      than in controls (P = 0.003). It seems that the level of salivary calcium
      concentration may be higher in menopausal women with OD feeling than in the
      control group.

PMID- 17448217
TI  - Oral lesions in HIV-positive dental patients--one more argument for tobacco
      smoking cessation.
AB  - OBJECTIVE: To determine the prevalence of oral lesions associated with human
      immunodeficiency virus (HIV) in a population of dental patients and analyze its
      association with psycho-social variables and biological markers. STUDY DESIGN:
      The dental charts of 415 dental patients consecutively treated between May and
      July 2005 in a dedicated HIV dental clinic were reviewed. Oral soft tissue
      examinations, psycho-social and medical variables were extracted and recorded for
      each patient. Ethnicity, gender, HIV treatment, peripheral CD(4) counts and
      tobacco usage were analyzed in correlation with oral lesions associated with HIV.
      RESULTS: Fifty-five percent of all subjects had at least one oral lesion
      associated with HIV, with oral candidiasis, salivary gland enlargement and oral
      hairy leukoplakia being the most commonly observed conditions. Gender and
      ethnicity did not correlate with a higher prevalence in lesions. However, tobacco
      smoking correlated significantly with a higher prevalence of oral lesions,
      independent of CD(4) counts. CONCLUSIONS: These findings suggest that oral
      lesions remain commonly observed morbidities among HIV-infected dental patients
      independent of gender and ethnicity and that tobacco usage is a major and often
      underestimated risk factor for those lesions.

PMID- 17448218
TI  - Detection of human herpesvirus 6 in patients with oral chronic graft-vs-host
      disease following allogeneic progenitor cell transplantation.
AB  - INTRODUCTION: Chronic graft-vs-host disease (cGVHD) is a major cause of morbidity
      in long-term survivors of allogeneic hematopoietic progenitor cell
      transplantation. Herpesviruses are involved in the occurrence and progression of
      various oral diseases. AIM: The aim of this study was to investigate the role of
      human herpesvirus 6 (HHV6) in patients with oral manifestations of cGVHD.
      MATERIALS AND METHODS: Peripheral blood and oral fluids (whole saliva, gingival
      crevicular fluid and parotid gland saliva) from 19 cGVHD patients, and 28 blood
      donors were examined for HHV6. Oral tissue samples were collected from 12 cGVHD
      patients and 12 healthy individuals. Nested polymerase chain reaction was
      employed to identify the HHV6. RESULTS AND CONCLUSION: The virus was detected in
      whole saliva in 13 cGVHD patients (68%) and in 19 blood donors (67%). HHV6 was
      not identified in any of the gingival crevicular fluid and parotid gland saliva
      samples in cGVHD patients. In the control group 14.3% of both, four gingival
      crevicular fluid and four parotid gland saliva samples were positive. Two oral
      tissue samples of cGVHD patients were positive for HHV6. These results indicate
      that patients with oral manifestations of cGVHD and healthy individuals present
      high and similar incidence of HHV6 in blood and oral fluids. These data do not
      support the importance of HHV6 in oral lesions of cGVHD.

PMID- 17448219
TI  - Oral leishmaniasis: a clinicopathological study of 11 cases.
AB  - Leishmaniasis is a parasitic disease with diverse clinical manifestations, and
      considered a public health problem in endemic countries such as Brazil. Mucosal
      lesions usually involve the upper respiratory tract, with a predilection for nose
      and larynx. Oral involvement is unusual and in most cases it becomes evident
      after several years of resolution of the original cutaneous lesions. Oral lesions
      classically appear as mucosal ulcerations, mainly in the hard or soft palate.
      This report describes the clinicopathological data of 11 cases of mucocutaneous
      leishmaniasis with oral manifestations. Two cases of Leishmania (Viannia)
      braziliensis and one case of Leishmania (Leishmania) amazonensis were confirmed
      by polymerase chain reaction-restriction fragment length polymorphism or DNA
      sequencing in mucosal samples.

PMID- 17448220
TI  - Metalloproteinase 9 is the outer executioner of desmoglein 3 in apoptotic
      keratinocytes.
AB  - OBJECTIVE: To investigate the specific matrix metalloproteinases (MMPs) targeting
      desmoglein 3 (Dsg3) in apoptotic keratinocytes. METHOD: Inhibitor studies on
      cultured keratinocytes and Western blot analysis. RESULTS: Blocking of MMP-9
      activity strongly reduces shedding of Dsg3 from cell surface. MMP-2 has a less
      relevant role in the cleavage of Dsg3 while other MMPs, such as MMP-1, -3, and 
      8, do not target Dsg3. CONCLUSION: Apoptic keratinocytes impair the extracellular
      domain of cell surface Dsg3 by MMP-9 activity. The discovery of a specific
      targeting of Dsg3 could be useful to understand the pathophysiology of diseases
      in which Dsg3 is affected.

PMID- 17448221
TI  - Bisphosphonate treatment as a cause of jaw osteonecrosis.

PMID- 17448222
TI  - A verification protocol for the probe sequences of Affymetrix genome arrays
      reveals high probe accuracy for studies in mouse, human and rat.
AB  - BACKGROUND: The Affymetrix GeneChip technology uses multiple probes per gene to
      measure its expression level. Individual probe signals can vary widely, which
      hampers proper interpretation. This variation can be caused by probes that do not
      properly match their target gene or that match multiple genes. To determine the
      accuracy of Affymetrix arrays, we developed an extensive verification protocol,
      for mouse arrays incorporating the NCBI RefSeq, NCBI UniGene Unique, NIA Mouse
      Gene Index, and UCSC mouse genome databases. RESULTS: Applying this protocol to
      Affymetrix Mouse Genome arrays (the earlier U74Av2 and the newer 430 2.0 array),
      the number of sequence-verified probes with perfect matches was no less than 85%
      and 95%, respectively; and for 74% and 85% of the probe sets all probes were
      sequence verified. The latter percentages increased to 80% and 94% after
      discarding one or two unverifiable probes per probe set, and even further to 84%
      and 97% when, in addition, allowing for one or two mismatches between probe and
      target gene. Similar results were obtained for other mouse arrays, as well as for
      human and rat arrays. Based on these data, refined chip definition files for all
      arrays are provided online. Researchers can choose the version appropriate for
      their study to (re)analyze expression data. CONCLUSION: The accuracy of
      Affymetrix probe sequences is higher than previously reported, particularly on
      newer arrays. Yet, refined probe set definitions have clear effects on the
      detection of differentially expressed genes. We demonstrate that the
      interpretation of the results of Affymetrix arrays is improved when the new chip
      definition files are used.

PMID- 17448223
TI  - Early postoperative bone scintigraphy in the evaluation of microvascular bone
      grafts in head and neck reconstruction.
AB  - BACKGROUND: Bone scintigraphy was performed to monitor anastomotic patency and
      bone viability. METHODS: In this retrospective study, bone scans were carried out
      during the first three postoperative days in a series of 60 patients who
      underwent microvascular bone grafting for reconstruction of the mandible or
      maxilla. RESULTS: In our series, early bone scans detected a compromised vascular
      supply to the bone with high accuracy (p < 10-6) and a sensitivity that was
      superior to the sensitivity of clinical monitoring (92% and 75% respectively).
      CONCLUSION: When performing bone scintigraphy during the first three
      postoperative days, it not only helps to detect complications with high accuracy,
      as described in earlier studies, but it is also an additional reliable monitoring
      tool to decide whether or not microvascular revision surgery should be performed.
      Bone scans were especially useful in buried free flaps where early postoperative
      monitoring depended exclusively on scans. According to our experience, we
      recommend bone scans as soon as possible after surgery and immediately in cases
      suspicious of vascularized bone graft failure.

PMID- 17448224
TI  - A cluster randomised controlled trial in primary dental care based intervention
      to improve professional performance on routine oral examinations and the
      management of asymptomatic impacted third molars: study protocol.
AB  - BACKGROUND: Routine oral examination (ROE) refers to periodic monitoring of the
      general and oral health status of patients. In most developed Western countries a
      decreasing prevalence of oral diseases underpins the need for a more
      individualised approach in assigning individualised recall intervals for regular
      attendees instead of systematic fixed intervals. From a quality-of-care
      perspective, the effectiveness of the widespread prophylactic removal of
      mandibular impacted asymptomatic third molars (MIM) in adolescents and adults is
      also questionable. Data on the effectiveness of appropriate interventions to
      tackle such problems, and for promoting continuing professional development in
      oral health care are rare. METHODS/DESIGN: This study is a cluster randomised
      controlled trial with groups of GDPs as the unit of randomisation. The aim is to
      determine the effectiveness and efficiency of small group quality improvement on
      professional decision-making of general dental practitioners (GDPs) in daily
      practice. Six peer groups ('IQual-groups') shall be randomised either to the
      intervention arm I or arm II. Groups of GDPs allocated to either of these arms
      act as each other's control group. An IQual peer group consists of eight to ten
      GDPs who meet in monthly structured sessions scheduled for discussion on practice
      related topics. GDPs in both trial arms receive recently developed evidence-based
      clinical practice guidelines (CPG) on ROE or MIM. The implementation strategy
      consists of one interactive IQual group meeting of two to three hours. In
      addition, both groups of GDPs receive feedback on personal and group
      characteristics, and are invited to make use of web-based patient risk vignettes
      for further individual training on risk assessment policy. Reminders (flow
      charts) will be sent by mail several weeks after the meeting. The main outcome
      measure for the ROE intervention arm is the use and appropriateness of
      individualised risk assessment in assigning recall intervals, and for the MIM
      intervention group the use and appropriateness of individualised mandibular
      impacted third molar risk management. Both groups act as each other's control.
      Pre-intervention data will be collected in study months one through three. Post
      intervention data collection will be performed after nine months.

PMID- 17448225
TI  - An adapted version of the long International Physical Activity Questionnaire
      (IPAQ-L): construct validity in a low-income, multiethnic population study from
      Oslo, Norway.
AB  - BACKGROUND: The aim was to assess the construct validity characteristics of an
      adapted version of the long International Physical Activity Questionnaire (IPAQ
      L) and report seasonal variations in physical activity (PA). METHODS: In two
      multiethnic suburbs of Oslo, Norway, all men and women aged 31-67 years (N =
      6140) were invited to a survey in 2000, and participants (N = 2950) were re
      invited in 2003. Complete IPAQ-L forms were delivered by 2274 baseline
      participants. We used the first IPAQ-L version, which asks for PA in a usual week
      with separate answering alternatives for summer and winter. Baseline energy
      expenditure calculated from IPAQ-L was compared with anthropometrical and
      biological measurements including maximal aerobic power in a subgroup, and
      individual changes in PA were compared with changes in these measurements.
      RESULTS: Vigorous PA within all domains, leisure-time PA (LPA), total PA, and in
      men occupational PA correlated with waist-to-hip ratio (rho around -0.1, p <
      0.05). For vigorous PA and LPA similar correlations were found with triglycerides
      and high-density lipoprotein-cholesterol (rho 0.1, p < 0.05). LPA was correlated
      with maximal aerobic power in both sexes with rho 0.2 for total LPA and 0.4 for
      vigorous LPA (p < 0.01). In men, similar correlations were found for changes in
      total vigorous PA. The overall energy expenditure reported was 18% higher in
      summer than in winter. The amount of total and commuting PA in the two seasons
      were highly correlated with rho values of 0.9 and 0.7, respectively (p < 0.01).
      CONCLUSION: Weak, but consistent correlations with baseline biological and
      anthropometrical measurements were found in both sexes, but for changes in PA
      such a pattern was seen in men only. The total energy expenditure in summer and
      winter were highly correlated although the absolute volume was higher in summer
      than in winter.

PMID- 17448226
TI  - Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic
      review.
AB  - INTRODUCTION: Severe sepsis and septic shock are common problems in the intensive
      care unit and carry a high mortality. Endotoxin, one of the principal components
      on the outer membrane of gram-negative bacteria, is considered important to their
      pathogenesis. Polymyxin B bound and immobilized to polystyrene fibers (PMX-F) is
      a medical device that aims to remove circulating endotoxin by adsorption,
      theoretically preventing the progression of the biological cascade of sepsis. We
      performed a systematic review to describe the effect in septic patients of direct
      hemoperfusion with PMX-F on outcomes of blood pressure, use of vasoactive drugs,
      oxygenation, and mortality reported in published studies. METHODS: We searched
      PubMed, the Cochrane Collaboration Database, and bibliographies of retrieved
      articles and consulted with experts to identify relevant studies. Prospective and
      retrospective observational studies, pre- and post-intervention design, and
      randomized controlled trials were included. Three authors reviewed all citations.
      We identified a total of 28 publications - 9 randomized controlled trials, 7 non
      randomized parallel studies, and 12 pre-post design studies - that reported at
      least one of the specified outcome measures (pooled sample size, 1,425 patients:
      978 PMX-F and 447 conventional medical therapy). RESULTS: Overall, mean arterial
      pressure (MAP) increased by 19 mm Hg (95% confidence interval [CI], 15 to 22 mm
      Hg; p < 0.001), representing a 26% mean increase in MAP (range, 14% to 42%),
      whereas dopamine/dobutamine dose decreased by 1.8 microg/kg per minute (95% CI,
      0.4 to 3.3 microg/kg per minute; p = 0.01) after PMX-F. There was significant
      intertrial heterogeneity for these outcomes (p < 0.001), which became non
      significant when analysis was stratified for baseline MAP. The mean arterial
      partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio
      increased by 32 units (95% CI, 23 to 41 units; p < 0.001). PMX-F therapy was
      associated with significantly lower mortality risk (risk ratio, 0.53; 95% CI,
      0.43 to 0.65). The trials assessed had suboptimal method quality. CONCLUSION:
      Based on this critical review of the published literature, direct hemoperfusion
      with PMX-F appears to have favorable effects on MAP, dopamine use, PaO2/FiO2
      ratio, and mortality. However, publication bias and lack of blinding need to be
      considered. These findings support the need for further rigorous study of this
      therapy.

PMID- 17448227
TI  - Single left coronary artery with separate origins of proximal and distal right
      coronary arteries from left anterior descending and circumflex arteries--a
      previously undescribed coronary circulation.
AB  - A single left coronary artery with right coronary artery arising from either left
      main stem (LMS) or left anterior descending artery (LAD) or circumflex artery
      (Cx) is an extremely rare coronary anomaly. This is the first report of separate
      origins of proximal and distal RCA from LAD and circumflex arteries respectively
      in a patient with a single left coronary artery. This 57 year old patient
      presented with unstable angina and severe stenotic disease of LAD and Cx arteries
      and underwent urgent successful quadruple coronary artery bypass grafting. The
      anomalies of right coronary artery in terms of their origin, number and
      distribution are reviewed.

PMID- 17448228
TI  - Lifestyle impact and the biology of the human scrotum.
AB  - The possession of a scrotum to contain the male gonads is a characteristic
      feature of almost all mammals, and appears to have evolved to allow the testes
      and epididymis to be exposed to a temperature a few degrees below that of core
      body temperature. Analysis of cryptorchid patients, and those with varicocele
      suggest that mild scrotal warming can be detrimental to sperm production, partly
      by effects on the stem cell population, and partly by effects on later stages of
      spermatogenesis and sperm maturation. Recent studies on the effects of clothing
      and lifestyle emphasize that these can also lead to chronically elevated scrotal
      temperatures. In particular, the wearing of nappies by infants is a cause for
      concern in this regard. Together all of the evidence indirectly supports the view
      that lifestyle factors in addition to other genetic and environmental influences
      could be contributing to the secular trend in declining male reproductive
      parameters. The challenge will be to provide relevant and targeted experimental
      results to support or refute the currently circumstantial evidence.

PMID- 17448229
TI  - Psychiatric diagnoses, trauma, and suicidiality.
AB  - BACKGROUND: This study aimed to examine the associations between psychiatric
      diagnoses, trauma and suicidiality in psychiatric patients at intake. METHODS:
      During two months, all consecutive patients (n = 139) in a psychiatric hospital
      in Western Norway were interviewed (response rate 72%). RESULTS: Ninety-one
      percent had been exposed to at least one trauma; 69 percent had been repeatedly
      exposed to trauma for longer periods of time. Only 7% acquired a PTSD diagnosis.
      The comorbidity of PTSD and other psychiatric diagnoses were 78%. A number of
      diagnoses were associated with specific traumas. Sixty-seven percent of the
      patients reported suicidal thoughts in the month prior to intake; thirty-one
      percent had attempted suicide in the preceding week. Suicidal ideation, self
      harming behaviour, and suicide attempts were associated with specific traumas.
      CONCLUSION: Traumatised patients appear to be under- or misdiagnosed which could
      have an impact on the efficiency of treatment.

PMID- 17448230
TI  - Risk factors of gastrointestinal nematode parasite infections in small ruminants
      kept in smallholder mixed farms in Kenya.
AB  - BACKGROUND: Helminth infections in small ruminants are serious problems in the
      developing world, particularly where nutrition and sanitation are poor. This
      study investigated the burden and risk factors of gastrointestinal nematode
      parasite infections in sheep and goats kept in smallholder mixed farms in the
      Kenyan Central Highlands. Three hundred and seven small ruminants were sampled
      from 66 smallholder mixed farms in agro-ecological zones 1 (humid) and 3 (semi
      humid) in the Kenyan Central highlands. The farms were visited once a month for
      eight months during which a health and production survey questionnaire was
      administered. Fecal samples were collected at each visit from each animal. Fecal
      egg counts (FEC) were performed using the modified McMaster technique.
      Associations between potential risk factors and FEC were assessed using 3-level
      Poisson models fit in SAS using GLIMMIX macro. Correlations among repeated
      observations were adjusted for using three different correlation structures.
      RESULTS: A rise in FEC was observed two months after the onset of rains. Farmer
      education, age category, de-worming during the preceding month and grazing system
      were significant predictors of FEC. Additionally, there were significant
      interactions between grazing system and both de-worming and age category implying
      that the effect of grazing system is dependent on both de-worming status and age
      category; and that the effect of de-worming depends on the grazing system. The
      most important predictors of FEC in the study area were grazing system, de
      worming status and education of the farmers. CONCLUSION: Since several factors
      were important predictors of FEC, controlling gastrointestinal helminths of small
      ruminants in these resource-poor smallholder mixed farms requires a sustainable
      integrated helminth control strategy that includes adoption of zero-grazing and
      more farmer education probably through extension services. Achieving improved
      helminth controls in these resource-poor farming systems offers an opportunity to
      increase small ruminant productivity and hence has a potential of improving the
      livelihood of the resource-poor farmers.

PMID- 17448231
TI  - Comparison of probabilistic choice models in humans.
AB  - BACKGROUND: Probabilistic choice has been attracting attention in
      psychopharmacology and neuroeconomics. Several parametric models have been
      proposed for probabilistic choice; entropy model, Prelec's probability weight
      function, and hyperbola-like probability discounting functions. METHODS: In order
      to examine (i) fitness of the probabilistic models to behavioral data, (ii)
      relationships between the parameters and psychological processes, e.g., aversion
      to possible non-gain in each probabilistic choice and aversion to
      unpredictability, we estimated the parameters and AICc (Akaike Information
      Criterion with small sample correction) of the probabilistic choice models by
      assessing the points of subjective equality at seven probability values (95%-5%).
      We examined both fitness of the models parametrized by utilizing AICc, and the
      relationships between the model parameters and equation-free parameter of
      aversion to possible non-gain. RESULTS: Our results have shown that (i) the
      goodness of fitness for group data was [Entropy model>Prelec's function>General
      hyperbola>Simple hyperbola]; while Prelec's function best fitted individual data,
      (ii) aversion to possible non-gain and aversion to unpredictability are distinct
      psychological processes. CONCLUSION: Entropy and Prelec models can be utilized in
      psychopharmacological and neuroeconomic studies of risky decision-making.

PMID- 17448233
TI  - Intestinal epithelial dysplasia (tufting enteropathy).
AB  - Intestinal epithelial dysplasia (IED), also known as tufting enteropathy, is a
      congenital enteropathy presenting with early-onset severe intractable diarrhea
      causing sometimes irreversible intestinal failure. To date, no epidemiological
      data are available, however, the prevalence can be estimated at around 1/50,000
      100,000 live births in Western Europe. The prevalence seems higher in areas with
      high degree of consanguinity and in patients of Arabic origin. Infants develop
      within the first days after birth a watery diarrhea persistent in spite of bowel
      rest and parenteral nutrition. Some infants are reported to have associated
      choanal rectal or esophageal atresia. IED is thought to be related to abnormal
      enterocytes development and/or differentiation. Nonspecific punctuated keratitis
      was reported in more than 60% of patients. Histology shows various degree of
      villous atrophy, with low or without mononuclear cell infiltration of the lamina
      propria but specific histological abnormalities involving the epithelium with
      disorganization of surface enterocytes with focal crowding, resembling tufts.
      Several associated specific features were reported, including abnormal deposition
      of laminin and heparan sulfate proteoglycan (HSPG) in the basement membrane,
      increased expression of desmoglein and ultrastructural changes in the desmosomes,
      and abnormal distribution of alpha2beta1 integrin adhesion molecules. One model
      of transgenic mice in which the gene encoding the transcription factor Elf3 is
      disrupted have morphologic features resembling IED. Parental consanguinity and/or
      affected siblings suggest an autosomal recessive transmission but the causative
      gene(s) have not been yet identified making prenatal diagnosis unavailable. Some
      infants have a milder phenotype than others but in most patients, the severity of
      the intestinal malabsorption even with enteral feeding make them totally
      dependent on daily long-term parenteral nutrition with a subsequent risk of
      complications. IED becomes an indication for intestinal transplantation, while
      timing of referral for it is crucial before the onset of severe complications.

PMID- 17448234
TI  - Contemporary management of drug-packers.
AB  - Experience with management of drug-packers (mules) is variable among different
      centres. However, despite a recorded increase in drug trafficking in general, as
      yet, no unified, clear guidelines exist to guide the medical management of those
      who only occasionally encounter these individuals. We describe our recent
      experience with this growing problem and discuss the most salient points
      concerning the contemporary management of body packers. Our recent experience
      demonstrates that type IV packages may now be managed conservatively for the most
      part.

PMID- 17448236
TI  - The skiers knee without swelling or instability, a difficult diagnosis: a case
      report.
AB  - Skiing as a recreational activity has increased exponentially in the last twenty
      years. Similar to any sporting activity, participants can sustain various types
      of injury, which provides the emergency departments with a continuous supply of
      patients. The injury pattern from the slopes has also changed over this time
      period, due to alterations and improvements in ski equipment. An increased
      diversity in alpine skiing techniques, as well as snowboarding and cross-terrain
      disciplines has also influenced this change.We present a multi-media experience
      of a high-speed ski fall that caused a valgus-external rotation injury to the
      right knee that precluded the patient from further ski activity. There was no
      bruising, swelling or instability demonstrated and the patient returned to ski
      activities 24-hours post-injury. Although this injury appeared clinically benign
      initially, the patient complained of persistent pain around the right knee which
      was causing occupational difficulties. Following normal clinical assessment, the
      patient returned to work but continued to complain of persistent pain at the
      lateral aspect of the right knee. Magnetic Resonance Imaging (MRI) demonstrated
      extensive bone marrow oedema (BMO), a mild depression of the articular cortex
      compression with a small focus of articular cartilage disruption and
      microfractures of the lateral tibial plateau. The patient was treated
      conservatively and remains well with avoidance of impact exercises 14-months post
      injury.In the presence of any high speed injury, we would stress that regardless
      of initial normal investigations, clinical suspicion should remain paramount and
      not deter the physician from further investigation in the presence of continuing
      symptomatology.

PMID- 17448235
TI  - A computational model of skeletal muscle metabolism linking cellular adaptations
      induced by altered loading states to metabolic responses during exercise.
AB  - BACKGROUND: The alterations in skeletal muscle structure and function after
      prolonged periods of unloading are initiated by the chronic lack of mechanical
      stimulus of sufficient intensity, which is the result of a series of biochemical
      and metabolic interactions spanning from cellular to tissue/organ level. Reduced
      activation of skeletal muscle alters the gene expression of myosin heavy chain
      isoforms to meet the functional demands of reduced mechanical load, which results
      in muscle atrophy and reduced capacity to process fatty acids. In contrast,
      chronic loading results in the opposite pattern of adaptations. METHODS: To
      quantify interactions among cellular and skeletal muscle metabolic adaptations,
      and to predict metabolic responses to exercise after periods of altered loading
      states, we develop a computational model of skeletal muscle metabolism. The
      governing model equations - with parameters characterizing chronic
      loading/unloading states- were solved numerically to simulate metabolic responses
      to moderate intensity exercise (WR < or = 40% VO2 max). RESULTS: Model
      simulations showed that carbohydrate oxidation was 8.5% greater in chronically
      unloaded muscle compared with the loaded muscle (0.69 vs. 0.63 mmol/min), while
      fat oxidation was 7% higher in chronically loaded muscle (0.14 vs. 0.13
      mmol/min), during exercise. Muscle oxygen uptake (VO2) and blood flow (Q)
      response times were 29% and 44% shorter in chronically loaded muscle (0.4 vs.
      0.56 min for VO2 and 0.25 vs. 0.45 min for Q). CONCLUSION: The present model can
      be applied to test complex hypotheses during exercise involving the integration
      and control of metabolic processes at various organizational levels (cellular to
      tissue) in individuals who have undergone periods of chronic loading or
      unloading.

PMID- 17448237
TI  - A mass accuracy sensitive probability based scoring algorithm for database
      searching of tandem mass spectrometry data.
AB  - BACKGROUND: Liquid chromatography coupled with tandem mass spectrometry (LC
      MS/MS) has become one of the most used tools in mass spectrometry based
      proteomics. Various algorithms have since been developed to automate the process
      for modern high-throughput LC-MS/MS experiments. RESULTS: A probability based
      statistical scoring model for assessing peptide and protein matches in tandem MS
      database search was derived. The statistical scores in the model represent the
      probability that a peptide match is a random occurrence based on the number or
      the total abundance of matched product ions in the experimental spectrum. The
      model also calculates probability based scores to assess protein matches. Thus
      the protein scores in the model reflect the significance of protein matches and
      can be used to differentiate true from random protein matches. CONCLUSION: The
      model is sensitive to high mass accuracy and implicitly takes mass accuracy into
      account during scoring. High mass accuracy will not only reduce false positives,
      but also improves the scores of true positive matches. The algorithm is
      incorporated in an automated database search program MassMatrix.

PMID- 17448238
TI  - Premortem clinical diagnoses and postmortem autopsy findings: discrepancies in
      critically ill cancer patients.
AB  - INTRODUCTION: Limited data are available regarding the relationship of premortem
      clinical diagnoses and postmortem autopsy findings in cancer patients who die in
      an oncologic intensive care unit (ICU). The purposes of this study were to
      compare the premortem clinical and postmortem diagnoses of cancer patients who
      died in the ICU and to analyze any discrepancies between them. METHODS: This is a
      retrospective review of medical records and autopsy reports of all cancer
      patients who died in a medical-surgical ICU and had an autopsy performed between
      1 January 1999 and 30 September 2005 at a tertiary care cancer center. Premortem
      clinical diagnoses were compared with the postmortem findings. Major missed
      diagnoses were identified and classified, according to the Goldman criteria, into
      class I and class II discrepancies. RESULTS: Of 658 deaths in the ICU during the
      study period, 86 (13%) autopsies were performed. Of the 86 patients, 22 (26%) had
      25 major missed diagnoses, 12 (54%) patients had class I discrepancies, 7 (32%)
      had class II discrepancies, and 3 (14%) had both class I and class II
      discrepancies. Class I discrepancies were due to opportunistic infections (67%)
      and cardiac complications (33%), whereas class II discrepancies were due to
      cardiopulmonary complications (70%) and opportunistic infections (30%).
      CONCLUSION: There was a discrepancy rate of 26% between premortem clinical
      diagnoses and postmortem findings in cancer patients who died in a medical
      surgical ICU at a tertiary care cancer center. Our findings underscore the need
      for enhanced surveillance, monitoring, and treatment of infections and
      cardiopulmonary disorders in critically ill cancer patients.

PMID- 17448239
TI  - A Rasch and factor analysis of the Functional Assessment of Cancer Therapy
      General (FACT-G).
AB  - BACKGROUND: Although the Functional Assessment of Cancer Therapy--General
      questionnaire (FACT-G) has been validated few studies have explored the factor
      structure of the instrument, in particular using non-sample dependent measurement
      techniques, such as Rasch Models. Furthermore, few studies have explored the
      relationship between item fit to the Rasch Model and clinical utility. The aim of
      this study was to investigate the dimensionality and measurement properties of
      the FACT-G with Rasch Models and Factor analysis. METHODS: A factor analysis and
      Rasch analysis (Partial Credit Model) was carried out on the FACT-G completed by
      a heterogeneous sample of cancer patients (n = 465). For the Rasch analysis item
      fit (infit mean squares > or = 1.30), dimensionality and item invariance were
      assessed. The impact of removing misfitting items on the clinical utility of the
      subscales and FACT-G total scale was also assessed. RESULTS: The factor analysis
      demonstrated a four factor structure of the FACT-G which broadly corresponded to
      the four subscales of the instrument. Internal consistency for these four scales
      was very good (Cronbach's alpha 0.72 - 0.85). The Rasch analysis demonstrated
      that each of the subscales and the FACT-G total scale had misfitting items (infit
      means square > or = 1.30). All these scales with the exception of the Social &
      Family Well-being Scale (SFWB) were unidimensional. When misfitting items were
      removed, the effect sizes and the clinical utility of the instrument were
      maintained for the subscales and the total FACT-G scores. CONCLUSION: The results
      of the traditional factor analysis and Rasch analysis of the FACT-G broadly
      agreed. Caution should be exercised when utilising the Social & Family Well-being
      scale and further work is required to determine whether this scale is best
      represented by two factors. Additionally, removing misfitting items from scales
      should be performed alongside an assessment of the impact on clinical utility.

PMID- 17448232
TI  - Characterisation of the genetic diversity of Brucella by multilocus sequencing.
AB  - BACKGROUND: Brucella species include economically important zoonotic pathogens
      that can infect a wide range of animals. There are currently six classically
      recognised species of Brucella although, as yet unnamed, isolates from various
      marine mammal species have been reported. In order to investigate genetic
      relationships within the group and identify potential diagnostic markers we have
      sequenced multiple genetic loci from a large sample of Brucella isolates
      representing the known diversity of the genus. RESULTS: Nine discrete genomic
      loci corresponding to 4,396 bp of sequence were examined from 160 Brucella
      isolates. By assigning each distinct allele at a locus an arbitrary numerical
      designation the population was found to represent 27 distinct sequence types
      (STs). Diversity at each locus ranged from 1.03-2.45% while overall genetic
      diversity equated to 1.5%. Most loci examined represent housekeeping gene loci
      and, in all but one case, the ratio of non-synonymous to synonymous change was
      substantially <1. Analysis of linkage equilibrium between loci indicated a
      strongly clonal overall population structure. Concatenated sequence data were
      used to construct an unrooted neighbour-joining tree representing the
      relationships between STs. This shows that four previously characterized
      classical Brucella species, B. abortus, B. melitensis, B. ovis and B. neotomae
      correspond to well-separated clusters. With the exception of biovar 5, B. suis
      isolates cluster together, although they form a more diverse group than other
      classical species with a number of distinct STs corresponding to the remaining
      four biovars. B. canis isolates are located on the same branch very closely
      related to, but distinguishable from, B. suis biovar 3 and 4 isolates. Marine
      mammal isolates represent a distinct, though rather weakly supported, cluster
      within which individual STs display one of three clear host preferences.
      CONCLUSION: The sequence database provides a powerful dataset for addressing
      ongoing controversies in Brucella taxonomy and a tool for unambiguously placing
      atypical, phenotypically discordant or newly emerging Brucella isolates.
      Furthermore, by using the phylogenetic backbone described here, robust and
      rationally selected markers for use in diagnostic assay development can be
      identified.

PMID- 17448241
TI  - A practical approach for implementation of a basal-prandial insulin therapy
      regimen in patients with type 2 diabetes.
AB  - Basal-prandial insulin therapy is a physiologic approach to insulin delivery that
      utilizes multiple daily injections to cover both basal (ie, overnight fasting and
      between-meal) and prandial (ie, glucose excursions above basal at mealtime)
      insulin needs. While basal-prandial therapy with multiple daily injections is an
      important therapeutic option for patients with type 2 diabetes, there is a common
      perception that this therapy is difficult to initiate in the primary care
      setting. To address this issue, a panel of clinical experts convened to develop
      practical recommendations on how to initiate basal-prandial therapy in patients
      with type 2 diabetes, focusing on patient selection, simple dosing and titration,
      and monitoring. Patients with type 2 diabetes who are appropriate candidates for
      basal-prandial insulin therapy include those who: 1) are unable to achieve
      glycemic control on oral antidiabetic drugs, 2) are unable to achieve glycemic
      control on split-mixed/premixed insulin regimens, 3) are newly diagnosed but
      unlikely to respond to oral antidiabetic drugs alone (ie, the patient has severe
      hyperglycemia or a markedly elevated glycosylated hemoglobin A1C level for which
      oral antidiabetic drug therapy alone is unlikely to achieve goals), and 4) prefer
      this therapy due to socioeconomic or other individual considerations. Basal
      prandial insulin can be initiated in a simple stepwise manner, starting first
      with the addition of basal insulin to the existing oral antidiabetic drug
      regimen, followed by the introduction of 1 prandial insulin injection to the
      basal insulin plus oral antidiabetic drug regimen (after basal insulin has been
      optimized). Subsequently, other injections of prandial insulin may be added when
      needed. Based on home glucose monitoring data, patients may be converted from
      split-mixed or premixed insulin regimens to basal-prandial regimens with similar
      ease. Basal-prandial therapy using newer insulin formulations, such as long- and
      rapid-acting insulin analogs, can be relatively simple to use in patients with
      type 2 diabetes and is an appropriate methodology for application by primary care
      clinicians.

PMID- 17448240
TI  - Monocyte-derived dendritic cells loaded with a mixture of apoptotic/necrotic
      melanoma cells efficiently cross-present gp100 and MART-1 antigens to specific
      CD8(+) T lymphocytes.
AB  - BACKGROUND: In the present study, we demonstrate, in rigorous fashion, that human
      monocyte-derived immature dendritic cells (DCs) can efficiently cross-present
      tumor-associated antigens when co-cultured with a mixture of human melanoma cells
      rendered apoptotic/necrotic by gamma irradiation (Apo-Nec cells). METHODS: We
      evaluated the phagocytosis of Apo-Nec cells by FACS after PKH26 and PKH67
      staining of DCs and Apo-Nec cells at different times of coculture. The kinetics
      of the process was also followed by electron microscopy. DCs maturation was also
      studied monitoring the expression of specific markers, migration towards specific
      chemokines and the ability to cross-present in vitro the native melanoma
      associated Ags MelanA/MART-1 and gp100. RESULTS: Apo-Nec cells were efficiently
      phagocytosed by immature DCs (iDC) (55 +/- 10.5%) at 12 hs of coculture. By 12-24
      hs we observed digested Apo-Nec cells inside DCs and large empty vacuoles as part
      of the cellular processing. Loading with Apo-Nec cells induced DCs maturation to
      levels achieved using LPS treatment, as measured by: i) the decrease in FITC
      Dextran uptake (iDC: 81 +/- 5%; DC/Apo-Nec 33 +/- 12%); ii) the cell surface up
      regulation of CD80, CD86, CD83, CCR7, CD40, HLA-I and HLA-II and iii) an
      increased in vitro migration towards MIP-3beta. DC/Apo-Nec isolated from HLA
      A*0201 donors were able to induce >600 pg/ml IFN-gamma secretion of CTL clones
      specific for MelanA/MART-1 and gp100 Ags after 6 hs and up to 48 hs of coculture,
      demonstrating efficient cross-presentation of the native Ags. Intracellular IL-12
      was detected in DC/Apo-Nec 24 hs post-coculture while IL-10 did not change.
      CONCLUSION: We conclude that the use of a mixture of four apoptotic/necrotic
      melanoma cell lines is a suitable source of native melanoma Ags that provides
      maturation signals for DCs, increases migration to MIP-3beta and allows Ag cross
      presentation. This strategy could be exploited for vaccination of melanoma
      patients.

PMID- 17448242
TI  - Spatial location and its relevance for terminological inferences in bio
      ontologies.
AB  - BACKGROUND: An adequate and expressive ontological representation of biological
      organisms and their parts requires formal reasoning mechanisms for their
      relations of physical aggregation and containment. RESULTS: We demonstrate that
      the proposed formalism allows to deal consistently with "role propagation along
      non-taxonomic hierarchies", a problem which had repeatedly been identified as an
      intricate reasoning problem in biomedical ontologies. CONCLUSION: The proposed
      approach seems to be suitable for the redesign of compositional hierarchies in
      (bio)medical terminology systems which are embedded into the framework of the OBO
      (Open Biological Ontologies) Relation Ontology and are using knowledge
      representation languages developed by the Semantic Web community.

PMID- 17448243
TI  - Continuous in situ measurements of volcanic gases with a diode-laser-based
      spectrometer: CO2 and H2O concentration and soil degassing at Vulcano (Aeolian
      islands: Italy).
AB  - We report on a continuous-measurement campaign carried out in Vulcano (Aeolian
      islands, Sicily), devoted to the simultaneous monitoring of CO2 and H2O
      concentrations. The measurements were performed with an absorption spectrometer
      based on a semiconductor laser source emitting around a 2-microm wavelength. The
      emitted radiation was selectively absorbed by two molecular ro-vibrational
      transitions specific of the investigated species. Data for CO2 and H2O
      concentrations, and CO2 soil diffusive flux using an accumulation chamber
      configuration, were collected at several interesting sampling points on the
      island (Porto Levante beach- PLB, Fossa Grande Crater - FOG- and Valley of
      Palizzi, PAL). CO2/H2O values, measured on the ground, are very similar (around
      0.019 (+/- 0.006)) and comparable to the previous discrete detected values of
      0.213 (Fumarole F5-La Fossa crater rim) and 0.012 (Fumarole VFS - Baia Levante
      beach) obtaid during the 1977-1993 heating phase of the crater fumaroles. In this
      work much more homogeneous values are found in different points of the three
      sites investigated. The field work, although carried out in a limited time window
      (25th-28th August 2004), pointed out the new apparatus is suitable for continuous
      gas monitoring of the two species and their ratios, which are important
      geochemical indicators of volcanic activity, for which other reliable continuous
      monitoring systems are not yet available.

PMID- 17448244
TI  - Error mapping controller: a closed loop neuroprosthesis controlled by artificial
      neural networks.

PMID- 17448245
TI  - epiPATH: an information system for the storage and management of molecular
      epidemiology data from infectious pathogens.
AB  - BACKGROUND: Most research scientists working in the fields of molecular
      epidemiology, population and evolutionary genetics are confronted with the
      management of large volumes of data. Moreover, the data used in studies of
      infectious diseases are complex and usually derive from different institutions
      such as hospitals or laboratories. Since no public database scheme incorporating
      clinical and epidemiological information about patients and molecular information
      about pathogens is currently available, we have developed an information system,
      composed by a main database and a web-based interface, which integrates both
      types of data and satisfies requirements of good organization, simple
      accessibility, data security and multi-user support. RESULTS: From the moment a
      patient arrives to a hospital or health centre until the processing and analysis
      of molecular sequences obtained from infectious pathogens in the laboratory, lots
      of information is collected from different sources. We have divided the most
      relevant data into 12 conceptual modules around which we have organized the
      database schema. Our schema is very complete and it covers many aspects of sample
      sources, samples, laboratory processes, molecular sequences, phylogenetics
      results, clinical tests and results, clinical information, treatments, pathogens,
      transmissions, outbreaks and bibliographic information. Communication between end
      users and the selected Relational Database Management System (RDMS) is carried
      out by default through a command-line window or through a user-friendly, web
      based interface which provides access and management tools for the data.
      CONCLUSION: epiPATH is an information system for managing clinical and molecular
      information from infectious diseases. It facilitates daily work related to
      infectious pathogens and sequences obtained from them. This software is intended
      for local installation in order to safeguard private data and provides advanced
      SQL-users the flexibility to adapt it to their needs. The database schema, tool
      scripts and web-based interface are free software but data stored in our database
      server are not publicly available. epiPATH is distributed under the terms of GNU
      General Public License. More details about epiPATH can be found at
      http://genevo.uv.es/epipath.

PMID- 17448246
TI  - Large genomic rearrangements in the CFTR gene contribute to CBAVD.
AB  - BACKGROUND: By performing extensive scanning of whole coding and flanking
      sequences of the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene,
      we had previously identified point mutations in 167 out of 182 (91.7%) males with
      isolated congenital bilateral absence of the vas deferens (CBAVD). Conventional
      PCR-based methods of mutation analysis do not detect gross DNA lesions. In this
      study, we looked for large rearrangements within the whole CFTR locus in the 32
      CBAVD patients with only one or no mutation. METHODS: We developed a semi
      quantitative fluorescent PCR assay (SQF-PCR), which relies on the comparison of
      the fluorescent profiles of multiplex PCR fragments obtained from different DNA
      samples. We confirmed the gross alterations by junction fragment amplification
      and identified their breakpoints by direct sequencing. RESULTS: We detected two
      large genomic heterozygous deletions, one encompassing exon 2 (c.54
      5811_c.164+2186del8108ins182) [or CFTRdele2], the other removing exons 22 to 24
      (c.3964-3890_c.4443+3143del9454ins5) [or CFTRdele 22_24], in two males carrying a
      typical CBAVD mutation on the other parental CFTR allele. We present the first
      bioinformatic tool for exon phasing of the CFTR gene, which can help to rename
      the exons and the nomenclature of small mutations according to international
      recommendations and to predict the consequence of large rearrangements on the
      open reading frame. CONCLUSION: Identification of large rearrangements further
      expands the CFTR mutational spectrum in CBAVD and should now be systematically
      investigated. We have designed a simple test to specifically detect the presence
      or absence of the two rearrangements identified in this study.

PMID- 17448247
TI  - Diagnostic value of anti-cyclic citrullinated peptide antibodies in Greek
      patients with rheumatoid arthritis.
AB  - BACKGROUND: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been of
      diagnostic value in Northern European Caucasian patients with rheumatoid
      arthritis (RA). In these populations, anti-CCP antibodies are associated with the
      HLA-DRB1 shared epitope. We assessed the diagnostic value of anti-CCP antibodies
      in Greek patients with RA where the HLA shared epitope was reported in a minority
      of patients. METHODS: Using an enzyme-linked immunosorbent assay (ELISA) (CCP2)
      kit, we tested anti-CCP antibodies in serum samples from 155 Greek patients with
      RA, 178 patients with other rheumatic diseases, and 100 blood donors. We also
      determined rheumatoid factor (RF) and compared it to anti-CCP antibodies for area
      under the curve (AUC), sensitivity, specificity and likelihood ratios. RESULTS:
      Sensitivity of anti-CCP2 antibodies and RF for RA was 63.2% and 59.1%, and
      specificity was 95.0% and 91.2%, respectively. When considered simultaneously,
      the AUC for anti-CCP antibodies was 0.90 with 95% CI of 0.87 to 0.93 and the AUC
      for RF was 0.71 with 95% CI of 0.64 to 0.77. The presence of both antibodies
      increased specificity to 98.2%. Anti-CCP antibodies were positive in 34.9% of RF
      negative RA patients. Anti-CCP antibodies showed a correlation with the
      radiographic joint damage. Anti-CCP-positive RA patients had increased the
      swollen joint count and serum CRP concentration compared to anti-CCP-negative RA
      patients (Mann-Whitney U test, p = 0.01, and p < 0.001, respectively). However,
      no correlation was found between anti-CCP antibodies and DAS28 score (r = 0.13, p
      = 0.12). CONCLUSION: In Greek patients with RA, anti-CCP2 antibodies exhibit a
      better diagnostic value than RF and a correlation with radiological joint damage
      and therefore are useful in everyday rheumatology practice.

PMID- 17448248
TI  - Predicting short-term weight loss using four leading health behavior change
      theories.
AB  - BACKGROUND: This study was conceived to analyze how exercise and weight
      management psychosocial variables, derived from several health behavior change
      theories, predict weight change in a short-term intervention. The theories under
      analysis were the Social Cognitive Theory, the Transtheoretical Model, the Theory
      of Planned Behavior, and Self-Determination Theory. METHODS: Subjects were 142
      overweight and obese women (BMI = 30.2 +/- 3.7 kg/m2; age = 38.3 +/- 5.8 y),
      participating in a 16-week University-based weight control program. Body weight
      and a comprehensive psychometric battery were assessed at baseline and at
      program's end. RESULTS: Weight decreased significantly (-3.6 +/- 3.4%, p < .001)
      but with great individual variability. Both exercise and weight management
      psychosocial variables improved during the intervention, with exercise-related
      variables showing the greatest effect sizes. Weight change was significantly
      predicted by each of the models under analysis, particularly those including self
      efficacy. Bivariate and multivariate analyses results showed that change in
      variables related to weight management had a stronger predictive power than
      exercise-specific predictors and that change in weight management self-efficacy
      was the strongest individual correlate (p < .05). Among exercise predictors, with
      the exception of self-efficacy, importance/effort and intrinsic motivation
      towards exercise were the stronger predictors of weight reduction (p < .05).
      CONCLUSION: The present models were able to predict 20-30% of variance in short
      term weight loss and changes in weight management self-efficacy accounted for a
      large share of the predictive power. As expected from previous studies, exercise
      variables were only moderately associated with short-term outcomes; they are
      expected to play a larger explanatory role in longer-term results.

PMID- 17448249
TI  - Analysis of health care and actual needs of patients with psoriasis: a survey on
      the Italian population.
AB  - BACKGROUND: Over recent years the public health system has shown increasing
      interest in patients' views for use as guideline criteria in evaluating the
      quality of assistance above all for those patients with chronic diseases. Hence
      the interest in psoriasis, which is a chronic disease frequently associated with
      diabetes mellitus, hypertension, obesity, and cardiovascular diseases. The aims
      of our study were to describe clinic characteristics of patients with psoriasis,
      the quality of the assistance perceived by patients arrived at outpatients
      clinics and the information received, in order to identify areas in Italy
      requiring improvement. METHODS: 1954 patients, aged between 18 and 85 years, were
      consecutively enrolled at outpatients clinics across 21 Italian provinces over
      the period December 2004-January 2006. A standardized questionnaire was developed
      in collaboration with an Italian Association of Psoriatic Patients (A.DI.PSO) and
      tested in a pilot study. The questionnaire was divided into three sections: the
      first section included social, demographic and individual variables; the second
      concerned the quality of the assistance perceived by the patients at public
      dermatologic clinics and the third focused on the need of information
      requirements of patients with psoriasis. The chi2 test was used to estimate the
      association between the categorical variables under study. Kruskal-Wallis test
      was applied to the interval and ordinal variables. RESULTS: The presence of
      psoriatic arthritis was reported in 26.0% of patients. Associated chronic
      diseases included depression (15.4%), hypertension (13.3%), obesity (8.9%) and
      type 2 diabetes mellitus (7.3%). The study highlighted the need of improvements
      of health care services at public dermatologic clinics especially in overcoming
      architectonic barriers and reducing appointment wait-times, particularly in South
      Italy. However, patients reported a positive relationship with Health System
      employers due to the confidentiality. This positive impression was confirmed by
      the observation that dermatologists were considered the best source of
      information about therapies on psoriasis. CONCLUSION: Our study allowed to
      identify critical aspects which could be tackled through initiatives with the aim
      of improving these emerged needs.

PMID- 17448250
TI  - Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis.
AB  - INTRODUCTION: The current shortage of accurate and readily available, validated
      biomarkers of disease severity in sepsis is an important limitation when
      attempting to stratify patients into homogeneous groups, in order to study
      pathogenesis or develop therapeutic interventions. The aim of the present study
      was to determine the cytokine profile in plasma of patients with severe sepsis by
      using a multiplex system for simultaneous detection of 17 cytokines. METHODS:
      This was a prospective cohort study conducted in four tertiary hospitals. A total
      of 60 patients with a recent diagnosis of severe sepsis were included. Plasma
      samples were collected for measurement of cytokine concentrations. A multiplex
      analysis was performed to evaluate levels of 17 cytokines (IL-1 beta, IL-2, IL-4,
      IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, interferon-gamma, granulocyte
      colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating
      factor, monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein
      1 and tumour necrosis factor-alpha). Cytokine concentrations were related to the
      presence of severe sepsis or septic shock, the severity and evolution of organ
      failure, and early and late mortality. RESULTS: Concentrations of IL-1 beta, IL
      6, IL-7, IL-8, IL-10, IL-13, interferon-gamma, MCP-1 and tumour necrosis factor
      alpha were significantly higher in septic shock patients than in those with
      severe sepsis. Cytokine concentrations were associated with severity and
      evolution of organ dysfunction. With regard to the severity of organ dysfunction
      on day 1, IL-8 and MCP-1 exhibited the best correlation with Sequential Organ
      Failure Assessment score. In addition, IL-6, IL-8 and G-CSF concentrations during
      the first 24 hours were predictive of worsening organ dysfunction or failure of
      organ dysfunction to improve on day three. In terms of predicting mortality, the
      cytokines IL-1 beta, IL-4, IL-6, IL-8, MCP-1 and G-CSF had good accuracy for
      predicting early mortality (< 48 hours), and IL-8 and MCP-1 had the best accuracy
      for predicting mortality at 28 days. In multivariate analysis, only MCP-1 was
      independently associated with prognosis. CONCLUSION: In this exploratory analysis
      we demonstrated that use of a multiple cytokine assay platform allowed
      identification of distinct cytokine profiles associated with sepsis severity,
      evolution of organ failure and death.

PMID- 17448251
TI  - Diagnosis of invasive candidiasis by enzyme-linked immunosorbent assay using the
      N-terminal fragment of Candida albicans hyphal wall protein 1.
AB  - BACKGROUND: The diagnosis of invasive candidiasis is difficult because there are
      no specific clinical manifestations of the disease and colonization and infection
      are difficult to distinguish. In the last decade, much effort has been made to
      develop reliable tests for rapid diagnosis of invasive candidiasis, but none of
      them have found widespread clinical use. RESULTS: Antibodies against a
      recombinant N-terminal fragment of the Candida albicans germ tube-specific
      antigen hyphal wall protein 1 (Hwp1) generated in Escherichia coli were detected
      by both immunoblotting and ELISA tests in a group of 36 hematological or
      Intensive Care Unit patients with invasive candidiasis and in a group of 45
      control patients at high risk for the mycosis who did not have clinical or
      microbiological data to document invasive candidiasis. Results were compared with
      an immunofluorescence test to detect antibodies to C. albicans germ tubes (CAGT).
      The sensitivity, specificity, positive and negative predictive values of a
      diagnostic test based on the detection of antibodies against the N-terminal
      fragment of Hwp1 by immunoblotting were 27.8 %, 95.6 %, 83.3 % and 62.3 %,
      respectively. Detection of antibodies to the N-terminal fragment of Hwp1 by ELISA
      increased the sensitivity (88.9 %) and the negative predictive value (90.2 %) but
      slightly decreased the specificity (82.6 %) and positive predictive values (80
      %). The kinetics of antibody response to the N-terminal fragment of Hwp1 by ELISA
      was very similar to that observed by detecting antibodies to CAGT. CONCLUSION: An
      ELISA test to detect antibodies against a recombinant N-terminal fragment of the
      C. albicans germ tube cell wall antigen Hwp1 allows the diagnosis of invasive
      candidiasis with similar results to those obtained by detecting antibodies to
      CAGT but without the need of treating the sera to adsorb the antibodies against
      the cell wall surface of the blastospore.

PMID- 17448252
TI  - Global analyses of mRNA translational control during early Drosophila
      embryogenesis.
AB  - BACKGROUND: In many animals, the first few hours of life proceed with little or
      no transcription, and developmental regulation at these early stages is dependent
      on maternal cytoplasm rather than the zygotic nucleus. Translational control is
      critical for early Drosophila embryogenesis and is exerted mainly at the gene
      level. To understand post-transcriptional regulation during Drosophila early
      embryonic development, we used sucrose polysomal gradient analyses and GeneChip
      analysis to illustrate the translation profile of individual mRNAs. RESULTS: We
      determined ribosomal density and ribosomal occupancy of over 10,000 transcripts
      during the first ten hours after egg laying. CONCLUSION: We report the extent and
      general nature of gene regulation at the translational level during early
      Drosophila embryogenesis on a genome-wide basis. The diversity of the translation
      profiles indicates multiple mechanisms modulating transcript-specific
      translation. Cluster analyses suggest that the genes involved in some biological
      processes are co-regulated at the translational level at certain developmental
      stages.

PMID- 17448253
TI  - Hepatoid carcinoma colliding with a liposarcoma of the left colon serosa
      presenting as an abdominal mass.
AB  - BACKGROUND: Hepatoid adenocarcinoma (HAC) is a peculiar type of extrahepatic
      adenocarcinoma generally characterized by adenocarcinomatous and hepatocellular
      carcinoma (HCC)-like foci. Stomach is the most frequent site where hepatoid
      adenocarcinoma occurs, although it has been described in many other organs. On
      the other side, liposarcoma is a rare, malignant tumor that develops from fat
      cells. CASE PRESENTATION: We describe here a case of hepatoid carcinoma in
      collision with a liposarcoma of the left colon serosa in a 71-year-old man. It
      presented as an abdominal mass involving several organs, falsely mimicking
      metastatic colonic adenocarcinoma. Recognition of this entity was evident on
      microscopic evaluation following surgery. The patient had an objective response
      following liposomal antracycline chemotherapy, with a 3-year overall survival.
      CONCLUSION: To our knowledge, this is the first case of a hepatoid tumor
      colliding with a liposarcoma of the left colon serosa reported to date.

PMID- 17448254
TI  - Implementing Baby Friendly Hospital Initiative policy: the case of New Zealand
      public hospitals.
AB  - BACKGROUND: Studies show that when the Baby Friendly Hospital Initiative (BFHI)
      is implemented breastfeeding rates increase. However, there are likely to be
      various barriers to BFHI implementation. This article reports on an empirical
      study of government-directed BFHI implementation in the New Zealand public
      hospital system. It focuses primarily on the barriers encountered through
      implementing the first Two Steps of the BFHI: developing BFHI policy and
      communicating it to staff; and providing necessary staff training. METHODS:
      Qualitative interview data were collected from six lactation consultants. These
      interviewees emerged via a purposive sample of public hospitals that represent
      the full range of New Zealand public hospitals. Using a content analysis
      technique, key themes were drawn from the transcribed interview data. RESULTS:
      Analysis revealed eight themes: the hospitals were in varying stages of BFHI
      policy development; hospital policy was not necessarily based on government
      policy; hospital policies were communicated in differing ways and dependent on
      resources; factors outside of hospital control impacted on capacity to improve
      breastfeeding rates; and complex organisational matters pose a barrier to
      educating personnel involved in the birthing process. CONCLUSION: The findings of
      this study provide empirical support for prior articles about the process of BFHI
      policy development and implementation. The study also shows that implementation
      is multi-faceted and complex.

PMID- 17448255
TI  - Phylogenetic and functional analysis of the Cation Diffusion Facilitator (CDF)
      family: improved signature and prediction of substrate specificity.
AB  - BACKGROUND: The Cation Diffusion Facilitator (CDF) family is a ubiquitous family
      of heavy metal transporters. Much interest in this family has focused on
      implications for human health and bioremediation. In this work a broad
      phylogenetic study has been undertaken which, considered in the context of the
      functional characteristics of some fully characterised CDF transporters, has
      aimed at identifying molecular determinants of substrate selectivity and at
      suggesting metal specificity for newly identified CDF transporters. RESULTS:
      Representative CDF members from all three kingdoms of life (Archaea, Eubacteria,
      Eukaryotes) were retrieved from genomic databases. Protein sequence alignment has
      allowed detection of a modified signature that can be used to identify new
      hypothetical CDF members. Phylogenetic reconstruction has classified the majority
      of CDF family members into three groups, each containing characterised members
      that share the same specificity towards the principally-transported metal, i.e.
      Zn, Fe/Zn or Mn. The metal selectivity of newly identified CDF transporters can
      be inferred by their position in one of these groups. The function of some
      conserved amino acids was assessed by site-directed mutagenesis in the poplar
      Zn2+ transporter PtdMTP1 and compared with similar experiments performed in
      prokaryotic members. An essential structural role can be assigned to a widely
      conserved glycine residue, while aspartate and histidine residues, highly
      conserved in putative transmembrane domains, might be involved in metal
      transport. The potential role of group-conserved amino acid residues in metal
      specificity is discussed. CONCLUSION: In the present study phylogenetic and
      functional analyses have allowed the identification of three major substrate
      specific CDF groups. The metal selectivity of newly identified CDF transporters
      can be inferred by their position in one of these groups. The modified signature
      sequence proposed in this work can be used to identify new hypothetical CDF
      members.

PMID- 17448256
TI  - Associations between sexual behaviour change in young people and decline in HIV
      prevalence in Zambia.
AB  - BACKGROUND: Evidence suggests that HIV prevalence amongst young Zambians has
      declined recently, especially in higher-education groups. We studied trends in
      key sexual behaviour indicators among 15-24 year-olds from 1995 to 2003,
      including the associations between sexual behaviour change and education.
      METHODS: The data stem from a series of three population-based surveys conducted
      in 1995 (n = 1720), 1999 (n = 1946) and 2003 (n = 2637). Logistic regression and
      Extended Mantel Haenszel Chi Square for linear trends were used to compare the
      three surveys. RESULTS: Men and lower-education groups reported more than one
      sexual partner in the year immediately prior to the survey more frequently than
      did women and higher-education groups (p < 0.01), but these proportions declined
      regardless of sex and residence. Substantial delays in child-bearing were
      observed, particularly among higher-education and urban respondents. Condom use
      at least for casual sexual intercourse increased from 1995 to 2003; the level was
      highest among urban and higher-education groups. The number of women reporting
      frequent dry sex using traditional agents fell during the period. Participants
      from the rural area and those with less education reported more sexual experience
      than urban and higher-education participants in 2003. The reported number of
      sexual partners during the year immediately prior to the survey was a factor that
      reduced the association between HIV and survey times among sexually active young
      urban men and women. CONCLUSION: High risk behaviours clearly decreased,
      especially in higher-educated and urban groups, and there is a probable
      association here with the decline in HIV prevalence in the study population.
      Fewer sexual partners and condom use were among the core factors involved for
      both sexes; and for women a further factor was delayed child-bearing.

PMID- 17448257
TI  - Metabolic syndrome in Thai schizophrenic patients: a naturalistic one-year follow
      up study.
AB  - BACKGROUND: Not only the prevalence, but also the progress of metabolic
      abnormalities in schizophrenic patients is of importance for treatment planning
      and policy making. However, there have been very few prospective studies of
      metabolic disturbance in schizophrenic patients. This study aimed to assess the
      progress of metabolic abnormalities in Thai individuals with schizophrenia by
      estimating their one-year incidence rate of metabolic syndrome (MetS). METHODS:
      We screened all schizophrenic patients who visited our psychiatric clinic. After
      the exclusion of participants with MetS at baseline, each subject was reassessed
      at 6 and 12 months to determine the occurrence of MetS. The definition of MetS,
      as proposed by the International Diabetes Federation (IDF), was applied. RESULTS:
      Fifty-seven participants (24 males and 33 females) had a mean of age and duration
      of antipsychotic treatment of 37.5 years old and 8.4 years, respectively. At
      baseline, 13 subjects met the MetS definition. Of 44 subjects who had no MetS at
      baseline, 35 could be followed up. Seven of these 35 subjects (20.0%) had
      developed MetS at the 6- or 12-month visit, after already having 2 MetS
      components at baseline. The demographic data and characteristics of those
      developing and not developing MetS were not different in any respect. CONCLUSION:
      Thai schizophrenic patients are likely to develop MetS. Their metabolic
      abnormalities may progress rapidly and fulfill the MetS definition within a year
      of follow-up. These findings support the importance of assessing and monitoring
      metabolic syndrome in schizophrenic patients.

PMID- 17448260
TI  - Pregnancy in women over 45: should this be encouraged?

PMID- 17448261
TI  - Thyroid dysfunction in perimenopausal and postmenopausal women.
AB  - Thyroid dysfunction is common, especially among women over the age of 50. In
      caring for peri- and post-menopausal women, it is important to recognize the
      changing clinical manifestations of thyroid disease with age. Postmenopausal
      women are at increased risk of both osteoporosis and cardiovascular disease, and
      untreated thyroid disease may exacerbate these risks. Screening for thyroid
      dysfunction in asymptomatic individuals is controversial, but aggressive case
      finding should be pursued, especially in older women. Women with overt thyroid
      dysfunction should be treated. Therapy for women with subclinical thyroid
      dysfunction is more controversial, although women with levels of thyroid
      stimulating hormone (TSH) > or =10 mU/L should be treated, and treatment may be
      considered in symptomatic women with subclinical hypothyroidism and TSH values
      <10 mU/L, and in women with subclinical hyperthyroidism who have TSH values
      consistently <0.1 mU/L. In women who are treated with thyroxine, careful dose
      titration and monitoring are required in order to prevent the adverse
      consequences of iatrogenic subclinical hyperthyroidism or hypothyroidism.
      Finally, caution is required in diagnosing and treating thyroid dysfunction in
      women who are taking oral estrogens or selective estrogen receptor modulators.

PMID- 17448262
TI  - Medical management of perimenopausal menorrhagia: an evidence-based approach.
AB  - About one-third of women report heavy menstrual bleeding at some time in their
      lives. Menstrual blood loss increases with age. Menorrhagia is usually defined as
      heavy but regular menstrual bleeding of over 80 ml/cycle. Complaints of
      menorrhagia are common. Several medical therapies are suitable for perimenopausal
      women with either regular or irregular heavy bleeding. The most effective is
      intrauterine levonorgestrel. Other options are oral progestogens, the combined
      oral contraceptive pill, tranexamic acid, mefenamic acid, danazol and
      gonadotrophin-releasing hormone (GnRH) analogues. Systematic reviews and
      randomized controlled trials are discussed.

PMID- 17448263
TI  - Diagnosis of cardiovascular disease in women.
AB  - Cardiovascular disease (CVD, comprising coronary heart disease and stroke) is the
      leading cause of death in both sexes in developed countries. Although women are
      nine times more likely to die from CVD than they are from breast cancer, there is
      a general public belief that the most common cause of death is cancer. The
      symptoms of acute myocardial infarction and acute coronary syndromes differ
      between the sexes. Women are less likely to experience chest pain and may have
      non-specific symptoms. Normal or non-obstructive coronary disease, as detected by
      angiography, is more common in women. Scintigraphy improves the detection of
      coronary disease in women. There is an urgent need to increase awareness of both
      coronary heart disease in women and the limitations of commonly used diagnostic
      tools.

PMID- 17448264
TI  - Homocysteine, menopause and cardiovascular disease.
AB  - A high plasma concentration of total homocysteine (tHcy) and a deficiency of
      vitamins related to its metabolism, such as vitamin B12 and folate, have been
      associated with cardiovascular disease. Postmenopausal women have higher
      concentrations than age-matched premenopausal women, and plasma concentrations of
      homocysteine in postmenopausal women taking hormone replacement therapy are
      significantly lower than they are in those who do not take estrogen supplements.
      Because of the possible mixed effects of HRT on cardiovascular events, surrogate
      end-points must be evaluated with caution. While measuring homocysteine levels is
      relatively simple, evidence from well designed trials is awaited before
      population screening can be advocated. Also, the benefits of reducing
      homocysteine levels with folic acid and vitamin B6 and B12 supplements are highly
      debated.

PMID- 17448265
TI  - The future of the new selective estrogen receptor modulators.
AB  - Selective estrogen receptor modulators (SERMs) are compounds that display mixed
      estrogen agonist/antagonist activity. Currently, four SERMs are licensed for
      clinical use: tamoxifen, toremifene, clomifene and raloxifene. The STAR and RUTH
      trials have provided useful data about the potential role of SERMs in the primary
      prevention of breast cancer and cardiovascular disease in postmenopausal women.
      New-generation SERMs, such as bazedoxifene, arzoxifene, lasofoxifene and
      ospemifene, are currently being evaluated. The aim is to find a SERM that
      conserves the skeleton and prevents breast cancer without increasing the risk of
      endometrial cancer and venous thromboembolism, and without inducing hot flushes.
      Technological advances in the study of estrogen receptor activation will provide
      key information for drug development.

PMID- 17448266
TI  - Calcium and vitamin D--for whom and when.
AB  - The basis of 'nutritional' interventions for the prevention of postmenopausal
      osteoporosis and osteoporotic fracture is a large topic with much genetic and
      biochemical evidence, as well as the results of randomized controlled trials, to
      guide the investigator and clinician. The efficacy of treatment with calcium and
      vitamin D was once controversial, but with the advent of controlled clinical
      trials using bone mineral density as an endpoint it has become clear that calcium
      with or without vitamin D therapy can lead to reductions in the rate of bone loss
      in postmenopausal women of all ages. Furthermore, with certain caveats, calcium
      with vitamin D therapy in the older postmenopausal woman can lead to useful
      reductions in fracture rates and falls, especially in populations with reduced
      exposure to sunlight, which is potentially the majority of postmenopausal women
      in both developed and developing countries. However, estrogen, selective estrogen
      receptor modulators (SERMs) and bisphosphonates (especially when given in
      combination with calcium and vitamin D) are more efficacious in preventing
      fracture, particularly in postmenopausal patients with impaired bone structure.

PMID- 17448267
TI  - Advances in the surgical management of prolapse.
AB  - Prolapse is an extremely common condition, for which 11% of women will have a
      surgical procedure at some point in their lives. The recurrence rate after most
      of the traditional surgical procedures is high and upto 29% of women who have had
      surgery for prolapse will require a further operation. In order to improve the
      surgical outcome, there is currently much interest in the use of grafts to
      augment traditional repairs and new procedures have been developed using
      specifically developed grafts. These have been combined with minimally invasive
      surgical techniques in an attempt to reduce surgical morbidity. These procedures
      may improve the outcome of surgery for prolapse. However, there is currently a
      lack of long-term data from randomized trials to demonstrate their effectiveness
      and safety.

PMID- 17448268
TI  - Management of premature menopause.
AB  - There has been some confusion among women and health professionals since the
      publication of the Women's Health Initiative and Million Women studies about the
      management of premature ovarian failure (POF). Both studies were undertaken in
      women aged 50 and over, and cannot be extrapolated to their younger counterparts,
      who would normally be producing their endogenous estrogen, since they have
      functioning ovaries. Estrogen-based replacement therapy is the main stay of
      treatment for women with POF and is recommended at least until the average age of
      natural menopause (52 years in the UK). This view is endorsed by regulatory
      bodies such as the Committee on Safety of Medicines (now the Commission on Human
      Medicines) in the UK. No evidence shows that estrogen replacement increases the
      risk of breast cancer to a level greater than that found in normally menstruating
      women, and women with POF do not need to start mammographic screening early
      unless other risk factors are present, such as family history.

PMID- 17448269
TI  - [Apoptosis of alveolar type II epithelial cells regulated by extracellular signal
      regulated kinase under oxidative stress].
AB  - OBJECTIVE: To investigate survival and apoptotic responses of alveolar type II
      epithelial cells (AT II cells) under oxidative stress and the regulation
      mechanism mediated by extracellular signal-regulated kinase (ERK). METHODS:
      Primary passage of cultured rat AT II cells were challenged with hydrogen
      peroxide (H(2)O(2)), and the cells were pretreated with specific inhibitor of ERK
      (PD 98059) in another group. Cell viability, apoptotic rate and the expression of
      phosphorylated ERK1/2 (p-ERK1/2)were measured by 3-(4, 5-dimethylthiazol-2-yl)-2,
      5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and Western blotting
      analysis, respectively. RESULTS: Compared with control group, decreased cell
      viability and increased apoptotic rate in AT II cells occurred in dose-dependent
      manner when treated with H(2)O(2) 500 and 1,000 micromol/L (all P<0.05), but no
      differences were found when H(2)O(2) were 10 and 100 micromol/L in
      concentrations. When the cells were treated with 500 micromol/L H(2)O(2) for 30
      minutes, no differences in cell viability and apoptotic rate were found compared
      with control group,but reduced cell viability and increased apoptotic rate were
      found when the duration was 180 minutes, and it was in time-dependent manner
      (both P<0.05). The expression of p-ERK peaked at 30 minutes after stimulation by
      500 micromol/L H(2)O(2). When PD 98059 was added, it enhanced apoptotic rate
      after H(2)O(2)-exposure. CONCLUSION: Apoptosis can be induced by H(2)O(2) in AT
      II cells in dose-and time-dependent manners. ERK signaling pathway plays a role
      in the regulation of apoptosis and may be protective for AT II cells under
      oxidative stress.

PMID- 17448270
TI  - [Experimental treatment of acute lung injury caused by inundation of thoracic
      cavity by seawater following open chest wound].
AB  - OBJECTIVE: To study the effects of lung protective ventilation and pentoxifylline
      (PTX) on acute lung injury (ALI) caused by open chest wound with seawater
      inundation of the thoracic cavity. METHODS: A model of ALI caused by open chest
      wound and seawater inundation of thoracic cavity was reproduced in dogs. Twenty
      four healthy dogs were randomly divided into four groups: no-treatment group
      (group A), ordinary treatment group (group B), lung protective ventilation
      treatment group (group C), and lung protective ventilation and PTX treatment
      group (group D). The parameters of hemodynamics, arterial blood gas analysis,
      plasma osmotic pressure and serum electrolytes in dogs were determined at 0 and 6
      hours after injury and at 2 and 4 hours after treatment. Blood samples and
      bronchoalveolar lavage fluid (BALF) were collected to assess the changes in
      cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6)
      and IL-8. RESULTS: The arterial oxygen partial pressure (PaO(2)) and oxygenation
      index (PaO(2)/FiO(2)) in group B were still lower than normal values at 2 and 4
      hours after treatment, but those parameters in group C and group D distinctly
      recovered. The parameters of hemodynamics, plasma osmotic pressure and serum
      electrolytes were all normalized in group B, C and D at 2 and 4 hours after
      treatment compared with those in group A. The levels of TNF-alpha in peripheral
      blood in group C and the TNF-alpha and IL-8 levels in peripheral blood and IL-6,
      IL-8 levels in BALF in group D were significantly lower than those in group A and
      group B after treatment. The TNF-alpha in peripheral blood and IL-8 levels in
      BALF in group D were also significantly lower than those in group C after
      treatment. CONCLUSION: Lung protective ventilation is an effective method in the
      treatment of ALI caused by open chest wound with inundation of seawater in
      thoracic cavity. PTX can inhibit inflammatory reaction in the lung and peripheral
      blood.

PMID- 17448271
TI  - [Epidemiological investigation on acute respiratory distress syndrome occurring
      in intensive care units in Beijing from 1998 to 2003].
AB  - OBJECTIVE: To investigate incidence, causes and mortality of acute respiratory
      distress syndrome (ARDS) in intensive care units (ICU) in Beijing. METHODS:
      Patients in ICU of eight general hospitals in Beijing from May 1998 to April 2003
      were retrospectively studied. ARDS was diagnosed according to the 1994 American
      European consensus conference criteria. Results Of 8 482 patients admitted to
      ICUs in the same period, there were 383 patients (4.5%) diagnosed as having ARDS.
      Major primary diseases for ARDS were sepsis (21.7%), pneumonia (16.2%), surgical
      operation (13.1%), acute pancreatitis (12.8%) and multiple severe trauma (10.7%).
      The mean interval between onset of the primary disease and onset of ARDS was
      (61.8 +/- 43.7) hours. The overall mortality of ARDS was 52.0%, the mortality
      adjusted for age (< or =39, 40-64, > or =65 years old) and gender (male) showed
      significant changes in each year (all P<0.05), but acute physiology and chronic
      health evaluation II (APACHE II, < or =12, 13-19, > or =20 scores) score showed
      no significant changes during the 5 years. Septic shock (36.2%) and heart failure
      (20.6%) were major lethal causes, while only 14.6% died of respiratory failure.
      CONCLUSION: ARDS was frequent in ICU in Beijing, the mortality remains high, and
      there is no tendency to decline in recent years.

PMID- 17448272
TI  - [Effect of diallyl trisulfide on tumor necrosis factor-alpha expression and
      nuclear factor-KappaB activity in mice with acute lung injury induced by
      lipopolysaccharide].
AB  - OBJECTIVE: To investigate the effect of diallyl trisulfide (DATS) on tumor
      necrosis factor-alpha (TNF-alpha) expression and nuclear factor-KappaB (NF
      KappaB) activity in mice with acute lung injury (ALI) induced by
      lipopolysaccharide (LPS). METHODS: ALI murine model was reproduced by injection
      of LPS intraperitoneally. Mice were randomly divided into normal saline control
      group, ALI group, DATS prevention group, DATS treatment group, and DATS control
      group. The TNF-alpha levels in the serum and in the supernatant of lung
      homogenates were measured with enzyme linked immunoadsorbent assay (ELISA). The
      expression of TNF-alpha mRNA in the lung tissues was detected by reverse
      transcription polymerase chain reaction (RT-PCR). NF-KappaB activity in the lung
      tissues was detected by electrophoresis mobility shift assay (EMSA). RESULTS: The
      levels of TNF-alpha induced by LPS in the serum and the supernatant of lung
      homogenates were increased markedly at 2 hours in ALI group (both P<0.01), and
      decreased at 6 hours, but they were still higher than those of the control groups
      (all P<0.01). They were reduced in DATS prevention group at 2 and 6 hours
      compared with those of ALI group (P<0.05 or P<0.01), but no change was noted in
      DATS treatment group (all P>0.05). The expression of TNF-alpha mRNA in the lung
      tissues of ALI group increased markedly at 2 hours compared with those of control
      groups (both P<0.01), and it could be down-regulated by pretreatment with DATS
      (P<0.05). No change in DATS was found in treatment group. NF-KappaB activity in
      the lung tissue increased in ALI group compared with that of control groups (both
      P<0.05), and it was markedly reduced in DATS prevention group (P<0.05), but no
      change was found in DATS treatment group. CONCLUSION: Pretreatment of DATS for
      ALI in mice could inhibit NF-KappaB activity, TNF-alpha mRNA expression in lung
      tissues, and decrease the release of TNF-alpha in the serum and the lung
      homogenates, and they might be the underlying mechanisms of prevention of the
      occurrence of ALI by DATS.

PMID- 17448273
TI  - [Pulmonary immune responses to acute lung injury following smoke inhalation and
      its mechanisms].
AB  - OBJECTIVE: To analyze pulmonary innate and specific immune responses following
      the smoke inhalation-induced acute lung injury (ALI). METHODS: Smoke inhalation
      induced ALI should be replicated at high (4x10(-3)) and low (2x10(-3)) dose of
      carbon monoxide (CO) respectively for 24 hours. After this period, lung tissue
      histopathological changes and the parameters of both treatment groups were
      observed compared to those of control animals: the phasic variations of
      concentrations of pro-anti-inflammatory cytokines in bronchoalveolar lavage fluid
      (BALF), numbers of lymphocyte subsets in peripheral blood and BALF, CD45(+)
      lymphoid leukocytes, CD45(+) nonlymphoid leukocytes and CD4(+)/CD8(+) in BALF
      were determined by flow cytometry (FCM). RESULTS: Lung histopathological changes
      of smoke-exposed animals revealed obvious alveolar leakage characterizing ALI.
      Concentrations of tumor necrosis factor-alpha (TNF-alpha) in BALF were increased
      immediately after injury and reached the peak at 2 hours after injury, and more
      obvious changes were seen in high dose group than those in low dose group. Levels
      of interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) were elevated following
      after 4 hours injury peaking at 12 hours. The changes of levels of IL-6 in low
      dose group were more obviously than those in high dose group, and those of IFN
      gamma were reverse. Levels of IL-6 and IFN-gamma were decreased at 24 hours,
      still higher than those of control group (P<0.05 or P<0.01), whereas the
      expressions of IL-10 were increased at 6 hours, and continuing upregulation to 24
      hours compared with those of control group (P<0.05 or P<0.01). Additionally, the
      numbers of lung-resident CD4(+) T cells, CD8(+) T cells, natural killer cells, B
      cells and total T-lymphocytes in peripheral blood and BALF were significantly
      reduced after challenge (P<0.05 or P<0.01). The number of CD45(+) lymphoid
      leukocytes in BALF and CD4(+)/CD8(+) were decreased; while that of CD45(+)
      nonlymphoid leukocytes was increased obviously compared with those of control
      group, and obviously changed in high dose group than in low dose group (P<0.05 or
      P<0.01). CONCLUSION: These data suggest that smoke inhalation induced ALI is
      associated with exaggerated and sustained pulmonary innate immune responses
      partly by activated polymorphonuclear neutrophils (PMN) and macrophage, whereas
      specific immunity in the lung is suppressed obviously.

PMID- 17448274
TI  - [Study of mucus secretion and aquaporin-5 expression of bronchial epithelium
      cultured in hypotonic medium].
AB  - OBJECTIVE: To study mucus secretion and aquaporin-5 (AQP5) expression of
      bronchial epithelium cultured at the air-liquid interface of hypotonic medium,
      and to elucidate the role of AQP5 and osmotic pressure in airway mucus
      hypersecretion process. METHODS: With the air-liquid interface culture model,
      rabbit tracheal epithelium was cultured at the air-liquid interface. One week
      after culture, media of 235, 255 and 270 mmol/L were used for experimental
      groups, and that of 282 mmol/L for culture in control group. Twelve hours after
      the culture, reverse transcriptase polymerase chain reaction (RT-PCR) was used to
      detect AQP5 mRNA in each experimental group, and Western blotting to determine
      mucin5AC (MUC5AC) in the supernatant. The same procedures were done in control
      group. RESULTS: Multilayers of cultured cells were observed with inverted
      microscope in each group. MUC5AC expressions in experimental groups were
      significantly higher, whereas AQP5 mRNA levels were obviously lower compared with
      those in control group (all P<0.001), the changes in 235 mmol/L group were most
      obvious. Moreover, AQP5 mRNA and MUC5AC in experimental groups were notably
      negatively correlated (r=-0.77, P<0.001). CONCLUSION: The model of air-liquid
      interface culture could increase MUC5AC expression, which provides an environment
      closely resembles that in the body is an ideal framework for the research of
      mucus hypersecretion of chronic obstructive pulmonary disease (COPD). Expressions
      of AQP5 mRNA and MUC5AC are negatively correlated. Hypotonicity and reduction of
      AQP5 mRNA may play critical roles in airway mucus secretion process in COPD.

PMID- 17448275
TI  - [Effects of 7-nitroindazole on smoke inhalation pulmonary injury].
AB  - OBJECTIVE: To investigate the effects of neuronal nitric oxide synthase (nNOS)
      inhibitor 7-nitroindazole (7-NI) on smoke inhalation pulmonary injury in rats.
      METHODS: Forty healthy male SD rats were randomly divided into three groups:
      control group (n=8), smoke inhalation model group (n=16) and 7-NI treatment group
      (n=16). After reproducing the smoke inhalation model, to the 7-NI treatment group
      rats 7-NI (20 mg/kg in 2 ml arachis oil) was administered by intraperitoneal
      injection, while in the control group and the model group, 2 ml arachis oil was
      administered by intraperitoneal injection. Arterial blood gas analysis was
      monitored at 2, 6, 12 and 24 hours. After rats were sacrificed, lung water was
      determined. The activities of super oxide dismutase (SOD), catalase (CAT), nitric
      oxide synthases (NOS), and the contents of tumor necrosis factor-alpha (TNF
      alpha), nitric oxide (NO) were determined in pulmonary tissue homogenate. The
      pathological changes in pulmonary tissue were observed under light microscope.
      RESULTS: Compared with model group, in 7-NI treatment group, arterial partial
      pressure of oxygen (PaO(2)) was elevated at each time point (all P<0.05), lung
      water was decreased (P<0.05). The activities of SOD and CAT were enhanced (all
      P<0.05), and the activities of nNOS and the content of NO were decreased (all
      P<0.05). TNF-alpha contents in lung tissues were decreased at 2 and 6 hours (both
      P<0.05). Pathological changes of less inflammatory cells infiltration and no
      punctate hemorrhage in lung interstitium in 7-NI treatment group than those in
      model group were seen under light microscope. CONCLUSION: 7-NI shows a good
      protective effect on smoke inhalation pulmonary injury, that it can raise PaO(2),
      increase the antioxidation ability, ameliorate lung edema and tissue inflammatory
      cells infiltration.

PMID- 17448276
TI  - [Treatment of foreign body in airway in children].

PMID- 17448277
TI  - [Protective effect of ATP sensitive potassium channel opener on cerebral
      ischemia/reperfusion injury and its signal transduction mechanism].
AB  - OBJECTIVE: To study the protective effect of ATP sensitive potassium channel(K(
      ATP))opener against neuronal apoptosis following focal cerebral
      ischemia/reperfusion (I/R) and its signal transduction mechanism. METHODS: Two
      hundred male Wistar rats were randomly divided into four groups: sham operation
      group (A group), I/R group (B group), K( ATP) opener treatment group (C group)
      and K( ATP) opener and blocker treatment group (D group). The middle cerebral
      artery occlusion (MCAO) by intraluminal suture method was used to reproduce
      cerebral ischemia, and perfusion was restored 2 hours after MCAO. Five rats in
      each group were used. Brain sections were made 6, 12, 24, 48 and 72 hours after
      I/R injury, and neuronal apoptosis was detected by terminal deoxynucleotidyl
      transferase-mediated deoxyuridine 5 triphosphate nick end labeling (TUNEL). The
      expressions of caspase-3 and caspase-9 proteins were detected by
      immunohistochemical method. Another five rats in each group were used for
      assessing the expressions of caspase-3 mRNA and caspase-9 mRNA by reverse
      transcription-polymerase chain reaction (RT-PCR). RESULTS: The number of
      apoptotic neurons, the expression of caspase-3 and caspase-9 mRNA and protein in
      B, C and D groups were significantly higher than A group at all time points
      (P<0.05 or P<0.01). The number of apoptotic neurons, the expressions of caspase-3
      and caspase-9 mRNA and protein in C group were significantly lower than B and D
      groups at all time points (P<0.05 or P<0.01). There were no differences between B
      and D groups at all time points (all P>0.05). CONCLUSION: K( ATP) opener can
      significantly mitigate neuronal apoptosis and inhibit the expressions of caspase
      3 and caspase-9 mRNA and protein after cerebral I/R injury. This result indicates
      that K( ATP) opener can decrease neuronal apoptosis by inhibiting mitochondria
      signaling pathway.

PMID- 17448278
TI  - [Effects of L. lactis recombinant heme oxygenase-1 gene on the intestinal barrier
      in rats with hemorrhagic shock].
AB  - OBJECTIVE: To evaluate the effect of gavage of L. lactis recombinant heme
      oxygenase-1 (HO-1) gene on protection of the intestinal mucosa and the
      inflammation of lower intestine during hemorrhagic shock. METHODS: A model of
      hemorrhagic shock was reproduced in 30 SD healthy male rats. They were randomly
      divided into the L. lactis recombinant HO-1 gene group (HO group, n=10), L.
      lactis group (LL group, n=10), and glutamine group (Glu group, n=10). Glu was
      gavaged 6 hours and other agents were gavaged 24 hours before the experiment.
      Samples were collected 1 hour after hemorrhagic shock and fluid resuscitation.
      The mortality, mean arterial pressure (MAP) during hemorrhagic shock and fluid
      resuscitation, myeloperoxidase (MPO) activity, the pathological changes, and the
      contents of HO-1, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL
      10) of the lower intestine were determined immunohistochemically and compared.
      RESULTS: When the results of HO group were compared with Glu and LL groups, the
      mortality was significantly decreased in the former (both P<0.05). In HO group,
      MAP values at 5, 10, 20 and 30 minutes after fluid resuscitation were
      significantly elevated (all P<0.05). Compared with LL group, the gray levels of
      IL-10 and HO-1 in HO group and Glu group were significantly increased (all
      P<0.05). Compared with Glu group, the gray level of HO-1 was significantly
      increased in HO group (P<0.05). There were no significant differences in the gray
      levels of TNF-alpha among three groups. The Chiu's grade of HO group [(1.41+/
      0.28) scores] was significantly lower than those of LL group and Glu group
      [(1.93+/-0.49) scores and (1.75+/-0.58) scores, respectively, both P<0.05].
      CONCLUSION: The L. lactis recombinant HO-1 has the virtue to deliver HO-1
      activity in rats with hemorrhagic shock, which is beneficial for the maintenance
      of intestinal barrier and anti-inflammation response of the lower intestine.

PMID- 17448279
TI  - [Effect of imatinib mesylate on bleomycin-induced pulmonary fibrosis in mice].
AB  - OBJECTIVE: To observe the effect of tyrosine kinase depressor imatinib mesylate
      on pulmonary fibrosis (PF) induced by bleomycin in mice and explore its
      mechanism. METHODS: One hundred and twenty C57BL/6 mice were randomly divided
      into control group, model group, dexamethasone group and imatinib mesylate group
      (with 30 mice each). After the model of PF was reproduced by a single
      intratracheal instillation of bleomycin, the above-mentioned drugs were given
      respectively. On 7, 14 and 21 days after treatment, 10 mice of each group were
      sacrificed, their lungs were harvested for measurement of the lung index,
      pathological change, concentration of hydroxyproline (HYP) and expression of
      platelet-derived growth factor-BB (PDGF-BB) in lung tissues. RESULTS: Lung
      indexes of model group were significantly higher than those of control group at
      different time points after in tracheal bleomycin (all P<0.05). Alveolitis grades
      and PF degrees were elevated markedly (all P<0.01). The concentrations of HYP in
      lung tissues were continuously increasing with the elapse of time after bleomycin
      (all P<0.05). The contents of PDGF-BB were obviously higher than those of control
      group (all P<0.05), and they gradually reduced with time. In imatinib mesylate
      and dexamethasone groups alveolitis grades and PF induced by bleomycin were
      obviously alleviated. The concentration of HYP and expression of PDGF-BB in lung
      tissues decreased in imatinib mesylate and dexamethasone groups compared with
      those in model group (P<0.05 or P<0.01). The effects of imatinib mesylate on
      above indexes were better than those of dexamethasone but without significant
      differences (all P>0.05). CONCLUSION: Imatinib mesylate may obviously inhibit the
      development of PF induced by bleomycin in mice.

PMID- 17448280
TI  - [Experimental study on detoxication effect of sulfhydryl compounds in acute
      poisoning of dimethylformamide].
AB  - OBJECTIVE: To study the change in oxidase and anti-oxidase in liver of the mice
      poisoned by dimethylformamide (DMF), and the effects of the treatment with
      sulfhydryl compounds in acute poisoning of DMF. METHODS: The sulfhydryl compounds
      included sodium dimercaptopropane (Na-DMPS), N-acetylcysteine (NAC), glutathione
      (GSH) and dimercaptosuccinic acid (DMSA). The model of acute poisoning with DMF
      in mice was reproduced, and the left hepatic lobes were harvested at 6, 12, 24,
      48 and 72 hours after DMF to detect the dynamic changes in the activities of
      superoxide dismutase (SOD) and xanthine oxidase (XOD) in liver homogenate.
      Treatment groups included intraperitoneal injection of Na-DMPS, NAC, GSH, DMSA
      respectively. In the control groups, the activities of XOD and SOD in liver were
      determined 24 hours after intragastric administration of DMF. RESULTS: The
      activities of XOD, SOD in liver were elevated at 24 hours after intragastric
      administration of DMF (both P<0.01), and returned to the normal levels at 48-72
      hours. Compared to the poisoning group, the activities of XOD, SOD in liver
      homogenate were significantly lowered after the treatment of Na-DMPS, NAC and
      DMSA (P<0.05 or P<0.01). The activity of XOD in liver homogenate was reduced 24
      hours after treating with GSH (P<0.05), and no obvious change was observed in SOD
      (P>0.05). As far as the activity of SOD was concentrated, Na-DMPS, NAC, DMSA
      showed better effects than GSH (all P<0.05), and Na-DMPS was the best. There was
      no significant differences in XOD among the four sulfhydryl compounds.
      CONCLUSION: The balance of oxidase and anti-oxidase is interrupted by DMF, which
      might be one of the mechanisms of damage to the liver. Na-DMPS, NAC and DMSA
      could protect liver function by restoring the balance.

PMID- 17448281
TI  - [Clinical control study of dialysates with different concentrations of calcium on
      blood pressure in patients under hemodialysis for prolonged period].
AB  - OBJECTIVE: To investigate the changes in blood pressure in hemodialysis patients
      treated with low calcium dialysate or high calcium dialysate for long time.
      METHODS: Fifteen patients undergoing hemodialysis were enrolled in this study.
      High calcium dialysate (1.75 mmol/L, Dca1.75) was first used for 6 months, then
      low calcium dialysate (1.25 mmol/L, Dca1.25) was used for 6 months. Serum
      calcium, phosphate, blood urea nitrogen, and creatinine were measured, blood
      pressure was recorded before and after hemodialysis at the beginning, and also at
      1, 2, 3 and 4 hours after hemodialysis. RESULTS: Compared with that before the
      treatment, systolic and diastolic blood pressure lowered significantly after
      single low calcium hemodialysis for 4 hours (both P<0.05), while systolic and
      diastolic blood pressure rose significantly after single high calcium
      hemodialysis (both P<0.05). Systolic blood pressure changed more obviously after
      two hemodialyses (both P<0.05). Changes in systolic, diastolic and mean blood
      pressure were positively related to changes in serum total calcium (r(1)=0.326,
      P(1)=0.054; r(2)=0.383, P(2)=0.037; r(3)=0.391, P(3)=0.032). During 6 months of
      hemodialysis with low calcium dialysate, blood pressure lowered slightly with no
      significant difference in it (P>0.05), while systolic blood pressure rose during
      6 months of hemodialysis with high calcium dialysate (P<0.05). Changes in
      systolic blood pressure were significantly different between two groups using
      dialysates with different calcium concentrations (P<0.05). CONCLUSION: Systolic
      blood pressure and incidence of hypertension decrease after single low calcium
      hemodialysis.

PMID- 17448282
TI  - [Effects of Xuebijing injection on high-mobility group box chromosomal protein 1
      in septic rats].

PMID- 17448283
TI  - [Hemodynamic variation in bolus doses or continuous infusion of adrenaline
      (epinephrine) during experimental cardiopulmonary resuscitation in rabbits with
      ventricular fibrillation].

PMID- 17448284
TI  - [Effect of cilazapril and valsartan on the levels of cardiac interstitial water
      content in rats with acute myocardial infarction].

PMID- 17448286
TI  - [Observation on changes in red cell deformability and lipid peroxidation in
      patients with acute ischemic cerebrovascular disease].

PMID- 17448285
TI  - [Study of the change in cardiac troponin I concentration by inhalation of nitrous
      oxide in patients with massive pulmonary embolism].

PMID- 17448287
TI  - [Study of treatment of hyaline membrane disease with pulmonary surfactant
      replacement in premature infant].

PMID- 17448288
TI  - [Effects of irbesartan on left ventricular diasolic function and heart rate
      variability of patients with acute myocardial infarction].

PMID- 17448289
TI  - [Prevention of embolism due to chronic auricular fibrillation with persantin
      (dipyridamole) combined with aspirin].

PMID- 17448290
TI  - [Clinical analysis of the effect of beta-blocker receptors in patients with
      chronic heart failure].

PMID- 17448291
TI  - [Development and clinical application of minimal invasive/non-invasive continuous
      hemodynamics monitoring system].

PMID- 17448292
TI  - [Study of surgical strategy of large area cerebellar infarction].

PMID- 17448293
TI  - Valproic acid, a molecular lead to multiple regulatory pathways.
AB  - Valproic acid (2-propyl pentanoic acid) is a drug used for the treatment of
      epilepsy and bipolar disorder. Although very rare, side effects such as spina
      bifida and other defects of neural tube closure indicate that valproic acid
      interferes with developmental regulatory pathways. Recently obtained data show
      that valproic acid affects cell growth, differentiation, apoptosis and
      immunogenicity of cultured cancer cells and tumours. Focused studies uncovered
      the potential of valproic acid to interfere with multiple regulatory mechanisms
      including histone deacetylases, GSK3 alpha and beta, Akt, the ERK pathway, the
      phosphoinositol pathway, the tricarboxylic acid cycle, GABA, and the OXPHOS
      system. Valproic acid is emerging as a potential anticancer drug and may also
      serve as a molecular lead that can help design drugs with more specific and more
      potent effects on the one side and drugs with wide additive but weaker effects on
      the other. Valproic acid is thus a powerful molecular tool for better
      understanding and therapeutic targeting of pathways that regulate the behaviour
      of cancer cells.

PMID- 17448295
TI  - Study of urinary proteomes in patients with nephrotic syndrome.
AB  - Heavy proteinuria may be caused by either increased glomerulal basement membrane
      permeability or membrane or podocyte structural damage, and also by impairment of
      secretion-reabsorption tubular processes. The precise composition of modified or
      degraded urine proteins in proteinuria is not known. However, a possible toxic
      effect of proteins on tubular cells and disease progression is assumed. In this
      study, 15 patients with nephrotic proteinuria and other diagnoses (systemic lupus
      erythematodes with renal involvement (lupus nephritis) and AAV) were analysed by
      the 2D electrophoresis method. We have studied sample stability during storage,
      the albumin separation effect on sample analyses using ammonium sulphate, and the
      effect of proteases on the protein spectrum. In the first step, the proteins were
      divided by the isoelectric focusing method using polyacrylamide strips (pH 3-10
      linear). The second step involved two-dimensional SDS electrophoresis performed
      in 12% polyacrylamide gel, which separated proteins according to their molecular
      weight. The proteins were visualized by the silver method. The gels were
      evaluated by Phoretix 2D expression software 2005. We found out that samples are
      stable for more than 6 months provided that they are frozen to -80 degrees C. The
      separation of albumin caused higher lucidity of the urinary proteomes. Without
      adding protease inhibitors we could detect proteolysis with increased quantity of
      proteins manifested in the area of about 10 kDa and decreased quantity of
      proteins detectable in the area with molecular weights about 50 kDa.

PMID- 17448294
TI  - Expansion of human mesothelial progenitor cells in a longterm three-dimensional
      organotypic culture of Processus vaginalis peritonei.
AB  - A 3D culture system was used to investigate the behaviour of mesothelial cells
      present in the wall of human processus vaginalis peritonei. Small tissue
      fragments placed on collagen sponges were cultured for 7, 14 and 21 days in
      medium supplemented with 10% FBS, and analysed for the expression and
      distribution of cytokeratins (CKAE1-AE3, CK19), p63, Ki-67, vimentin, CD34, and
      HBME-1. Before culture, flat mesothelial cells displayed immunoreactivity for
      cytokeratins, vimentin and HBME-1, while p63 and CD34 were negative. Mesenchymal
      cells within the stroma were vimentin-positive and endothelial cells of small
      vessels displayed positive staining for CD34. Cytokeratins, p63 and HBME-1 were
      negative in all stromal cells. In cultured fragments, flat mesothelial cells
      positive for vimentin, cytokeratins and HBME-1 proliferated, lining the fragment
      surface and migrating into the sponge. Capillaries showed morphological
      alterations; however, their immunoreactivity was comparable with the stroma prior
      to culture. Cells that had migrated into the sponge and displayed characteristics
      of mesothelial progenitors, predominantly spindleshaped and stellate, showed
      heterogeneous expression of markers especially in late phases of cultivation.
      These cells were constantly positive for vimentin, a small fraction was
      cytokeratin-positive and a few displayed HBME-1 immunoreactivity. CD34 was found
      in cells forming small cavities into the matrix, resembling newly formed blood
      vessels. Cells that had migrated into the sponge could be isolated and expanded
      in coculture with feeder NIH.3T3 fibroblasts. This system is suitable for
      studying growth and behaviour of mesothelial cells within their natural
      environment, providing a good method for isolation and expansion of their
      progenitor cells.

PMID- 17448296
TI  - Collagen degradation products and proinflammatory cytokines in systemic and
      localized scleroderma.
AB  - The aim of this study was to assess the degradation of collagen type I and
      proinflammatory cytokines in systemic and localized scleroderma compared with
      psoriasis and healthy controls. Total 99 individuals were examined - 24 with SSc,
      22 with LSc, 39 patients with PsV and 14 healthy controls. U-PD and U-DPD were
      measured using a sensitive isocratic HPLC method. Serum levels of IL-6 and
      soluble IL-2R were assayed using commercial ELISA kits. In the SSc group U-PD and
      U-DPD levels (nmol/mmol creatinine) were increased compared with controls (P =
      0.001) and with PsV (P = 0.006). IL-6 levels were increased compared with
      controls (P = 0.004) and with PsV (P = 0.002). IL-2R concentrations were
      insignificantly increased in comparison with controls and were lower than in PsV,
      but the difference was not significant. In the LSc group excretion of U-PD and U
      DPD did not differ from controls, but was insignificantly decreased compared with
      PsV. IL-6 levels were increased compared with controls (P = 0.001) and also with
      PsV (P = 0.03). IL-2R concentrations were significantly increased in comparison
      with controls only (P = 0.03). In patients with SSc our data have shown the most
      intensive collagen degradation and simultaneously an active inflammation, as
      documented by IL-6, which reflects the pathological processes in the skin and
      visceral organs compared with PsV patients and healthy individuals. In the LSc
      group collagen degradation was similar to that in control groups, but a certain
      inflammatory activity was observed.

PMID- 17448297
TI  - M235T polymorphism of the angiotensinogen gene and insertion/deletion
      polymorphism of the angiotensin-1 converting enzyme gene in essential arterial
      hypertension in Caucasians.
AB  - In order to investigate the contribution of candidate genes in the RAAS in
      pathogenesis of EAH, we analysed the M235T polymorphism of the angiotensinogen
      gene, and the I/D polymorphism of ACE gene in a group of adult Caucasians
      (Slovene population) with EAH. Four-hundred and thirteen unrelated subjects with
      the diagnosis of EAH were included in the association study and they were
      compared to 414 subjects with normal blood pressure (the control group). The
      M235T angiotensinogen genotype distribution in patients with EAH (TT = 23.2%, MT
      = 48.7%, MM = 28.1%) did not differ from genotype distribution in controls (TT =
      21.1%, MT = 49.0%, MM = 29.9%), and the TT genotype was not associated with EAH
      (OR 1.1; 95% CI 0.7-1.7; P = 0.6). Moreover, The I/D ACE genotype distribution in
      patients with EAH (DD = 32.0%, ID = 48.2%, II = 19.8%) did not differ from
      genotype distribution in controls (DD = 32.2%, ID = 49.0%, II = 18.8%), and the
      DD genotype was not associated with EAH (OR 1.0; 95% CI 0.7-1.3; P = 0.9). In
      conclusion, we failed to demonstrate that the M235T angiotensinogen polymorphism
      and the ACE I/D polymorphism were genetic markers for EAH in adult Caucasians.

PMID- 17448298
TI  - [Evidence-based therapy of pediatric kidney disease].

PMID- 17448299
TI  - [Molecular pathological basis and prevention and therapy strategies of pediatric
      chronic kidney disease].

PMID- 17448300
TI  - [Pediatric renal transplant].

PMID- 17448301
TI  - [Clinical evidence of therapy of IgA nephropathy].

PMID- 17448302
TI  - [Progress of renal replacement therapy in children].

PMID- 17448303
TI  - [Clinical application and side effects of immunosuppressant].

PMID- 17448304
TI  - [Treatment of hereditary renal disease].

PMID- 17448305
TI  - [Clinicopathologic characteristics of 1,316 children with renal disease].
AB  - OBJECTIVE: To investigate the clinicopathologic characteristics of childhood
      renal diseases. METHODS: A retrospective analysis of 1316 renal biopsies
      performed over the past 20 years was performed. RESULTS: Of the 1316 patients,
      383 (29.09% ) were diagnosed as nephrotic syndrome, 291 (22.00%) as acute
      nephritis syndrome, 224 (17.21%) as isolated hematuria, 209(15.87%) as purpura
      nephritis, and 96 (7.30% ) as hepatitis B virus-associated nephritis . Mesangial
      proliferation was the most common pathological change (756 cases; 57.45%),
      followed by IgA nephropathy (113 cases; 8.59%), endothelial capillary
      proliferation(112 cases; 8.51%), membranous nephropathy (66 cases; 5.02%), and
      various minor and minimal changes (59 cases; 4.48%). Alport syndrome, congenital
      nephrotic syndrome, thin basement membrane nephropathy, fibrillary glomerulopathy
      disease, and Fabry disease were confirmed by electronic microscopy. IgA, IgM and
      C1q nephropathy were definitely diagnosed using immune histochemistry or
      immunofluorescent. A diagnosis of primary glomerular disease was made in 69.53%
      of the cases (915 cases); secondary glomerular disease was noted in 26.14% (344
      cases). Of the 915 cases of primary glomerular disease, 375 (41.0%) had nephrotic
      syndrome. Secondary glomerular disease due to purura nephritis was common
      (209/344; 60.8%). CONCLUSIONS: Primiary glomerular disease predominates in
      children. Nephrotic syndrome is the most common clinical diagnosis. Mesangial
      proliferation is the most common pathological patterns in children with renal
      disease.

PMID- 17448306
TI  - [Establishment of urinary proteomic map on two-dimensional polyacrylamide gel
      electrophoresis in children with idiopathic nephrotic syndrome].
AB  - OBJECTIVE: To establish a urinary proteomic map on two-dimensional polyacrylamide
      gelelectrophoresis (2-DE) in children with idiopathic nephrotic syndrome (INS).
      METHODS: The proteins from INS children were purified by four various means,
      separated by 2-DEand stained by silver. RESULTS: The sequential preparation of
      urinary proteins by acetone precipitation and dislysis, when the sample was 300
      microg, resulted in a clear background, well-resolved and reproducible 2-DE
      urinary protemic map in children with INS. CONCLUSIONS: A steady 2-DE technique
      for urinary protemic map in children with INS was established, which can be
      effectively applied in urinary proteomics of the disease.

PMID- 17448307
TI  - [Role of mast cells in the development of renal interstitial fibrosis in children
      with Henoch-Schonlein purpura nephritis].
AB  - OBJECTIVE: To investigate the role of mast cells in the development of renal
      interstitial fibrosis in children with Henoch-Schonlein purpura nephritis (HSPN)
      and possible mechanisms. METHODS: Paraffin-embedded renal biopsy tissue sections
      from 20 children with HSPN were examined for the levels of tryptase-beta and
      transforming growth factor-beta1 (TGF-beta1) by immunohistochemical staining.
      Mast cells were counted by toluidine blue staining. Masson staining was used to
      assess the level of renal interstitial fibrosis and renal histopathological
      scores. Normal renal tissue sections from 5 nephrectomized children for nephroma
      were used as control group. RESULTS: The percentages of positive tryptase-beta
      cellsand mast cells and the TGF-beta1 expression in the HSPN group were
      significantly higher than those in the control group (P < 0.05). The percentages
      of positive tryptase-beta cells and mast cells and the TGF-beta1 expression in
      renal tissue were positively correlated with the glomeruli histopathological
      score (r =0.940, 0.920, 0.937, respectively; P < 0.05) and were also positively
      correlated with the histopathological score of renal interstitium (r=0.903,
      0.859, 0.948, respectively; P < 0.05). The level of renal interstitial fibrosis
      was positively correlated with the percentages of positive tryptase-beta cells
      and mast cells and the expression of TGF-beta1 (r =0.790, 0.766, 0.858,
      respectively; P < 0.05). There was a positive correlation between the percentages
      of positive tryptase-beta cells and mast cells (r =0.941, P < 0.05), between the
      percentage of positive tryptase-beta cells and the TGF-beta1 expression (r
      =0.897, P < 0.05) and between the percentage of positive mast cells and the TGF
      beta1 expression (r=0.942, P < 0.05). CONCLUSIONS: Tubulointerstitial mast cell
      infiltration is associated with the development of renal interstitial fibrosis in
      children with HSPN. Mast cells together with TGF-beta1 and mast cell-derived
      tryptase-beta may be involved in the development of the renal interstitial
      fibrosis in HSPN.

PMID- 17448308
TI  - [Relationship between clinical manifestations and renal pathology in children
      with Henoch-Schonlein purpura nephritis].
AB  - OBJECTIVE: This study investigated the clinical manifestations and renal
      pathological findings of 95 children with Henoch-Schonlein purpura nephritis
      (HSPN) in order to explore the relationship between clinical manifestations and
      renal pathology in HSPN. METHODS: According to clinical manifestations, 95 HSP
      patients were classified into six clinical groups: 1) normal urine analysis; 2)
      isolated hematuria or proteinuria; 3) proteinuria with hematuria; 4) acute
      nephritis; 5) nephrotic syndrome; 6) acute nephritis with over 50 mg/(kg.d) of
      proteinuria. The severity of the renal pathological findings was determined based
      on the classification of the International Study of Kidney Disease (ISKDC),
      including grades I-VI. The relationship between clinical manifestations and the
      severity of renal pathological findings was studied. RESULTS: Nephrotic syndrome
      was the most common clinical diagnosis (26 cases), followed by proteinuria with
      hematuria (23 cases), normal urine analysis (20 cases), isolated hematuria or
      proteinuria (15 cases), acute nephritis with over 50 mg/(kg.d) of proteinuria (7
      cases) and acute nephritis (4 cases). Twenty-five out of 26 patients with
      nephrotic syndrome had an ISKDC classification of grade III-IV. All of the four
      patients with acute nephrits had a classification of grade IIIb. The 7 cases of
      acute nephritis with over 50 mg/(kg.d) of proteinuria had a classification of
      grade IIIa-V. The 20 patients with normal urine analysis had a classification of
      grade Iia- IIIb. There were no significant differences in ISKDC classification
      among the patients with normal urine analysis, isolated hematuria or proteinuria,
      and hematuria plus proteinuria. As the course progressed, the degree of renal
      pathological changes in patients with isolated hematuria or proteinuria and
      hematuria plus proteinuria became more serious. Of all the 95 patients, 58% had
      co-deposition of immunoglobulins A, G and M. The percentage of co-deposition of
      immunoglobulins A, G and M was related to the disease course and the severity of
      renal pathological findings. CONCLUSIONS: HSPN children with nephrotic syndrome
      or acute nephritis with or without proteinuria had relatively severe renal
      pathological changes. The clinical manifestations were not always in parallel
      with the severity of renal pathological findings in HSPN children. With the
      course progressing, the renal pathological changes tended to be serious. The
      severe renal pathological manifestations came with co-deposition of
      immunogolobulins A, G and M in the glomerulin.

PMID- 17448309
TI  - [Expression of fibroblast growth factor receptor-4 in fetal kidneys and
      pathological kidneys of children].
AB  - OBJECTIVE: To investigate the expression of fibroblast growth factor receptor-4
      (FGFR4) in fetal kidneys and pathological kidneys of children in order to show
      the roles of fibroblast growth factor (FGF) and FGFR4 in the development of fetal
      kidneys and renal diseases. METHODS: The expression of FGFR4 was detected by
      immumohistochemistry in the normal fetal kidney at 8 to 34 weeks of gestation age
      (n=18) and 82 children with renal disease, including 28 cases of primary
      nephrotic syndrome (PNS), 12 acute glomerulonephritis (AGN), 20 Henoch-Schoenlein
      purpura nephritis (HSPN), and 22 isolated hematuria (IHU). A correlation analysis
      between renal pathological scores and FGFR4 expression was performed. RESULTS: 1)
      FGFR4 expression was weakly in renal vesicle and primitive tubules of S-shaped
      body, irrecognizable in urteric bud and podocytes of C-stage, and negative in
      mesenchyme and condensing mesenchyme. The immunostaining of FGFR4 was intense in
      distal tubules and collecting ducts, but was negative in mature glomeruli and
      proximal tubules. 2) FGFR4 was expressed in all pathological sections of various
      renal diseases. FGFR4 expression was intense in tubules but weak in glomeruli. It
      was principally expressed in distal tubules and partially in proximal tubules.
      The tubules with very strong expressions of FGFR4 presented abnormal structures
      including dilation and atrophy, especially in proximal tubules. 3) There were no
      significant differences in the FGFR4 expression in various parts of the kidney
      among various renal diseases. There were also no significant differences in the
      FGFR4 expression in renal tubules among the four different pathological types of
      renal diseases: focal segmental glomerularsclerosis (FSGS), membranoproliferative
      glomerulonephritis (MPGN), mesangial proliferative glomerulonephritis (MsPGN),
      and minimal change disease (MCD). The FGFR4 expression in podocytes in the MPGN
      group was noticeably higher than that of the other pathological type group (P <
      0.05). 4) The FGFR4 expression in proximal tubules positively correlated with the
      pathological score of tubules (r=0.463682, P < 0.05) but negatively correlated
      with the pathological score of glomeruli (r=- 0.0277, P < 0.05). The FGFR4
      expression in both distal tubules and podocytes negatively correlated with the
      pathological score of tubules or glomeruli (P < 0.05). CONCLUSIONS: The
      development of fetal kidneys in the early period could not be regulated by FGF
      FGFR4 signal which takes part in the development of renal tubules and collecting
      duct in the mature period. The FGFR4 expression is related with renal pathology
      in children with PNS, AGN, HSPN or IHU. A proper increase of FGFR4 expression is
      beneficial to the recovery of renal tissues but an over-expression relates to a
      severe renal damage.

PMID- 17448310
TI  - [Evidence-based therapy of nephrotic edema].
AB  - OBJECTIVE: To study the evidence-based therapy of edema in nephrotic syndrome by
      analyzing the literatures systematically. METHODS: The literatures related to the
      treatment of nephrotic edema were retrieved from the following: Chinese
      Biological Medicine Database (CBM-disk), Chinese Journals Full-text Database
      (CNKI, 1994-2006), Chinese Technological Periodicals Database (VIP, 1989-2006),
      Chinese Evidence Biological Medicine/Cochrane Central Database (CEBM/CCD),
      Cochrane Library Database, MEDLINE (1966-2006), EMBASE (1975-2006), MEDLARS, SCI
      (1985-2006) and OVID by electron and craft search with the following key words:
      nephrotic syndrome, edema, recalcitrant edema, refractory edema or resistant
      nephrotic edema, and treatment, diuretic therapy or human albumin treatment. The
      relevant literatures on randomized controlled trials (RCT) that met the criteria
      were statistically analyzed by the Coorporative network software RevMan 4.2.
      RESULTS: A total of 113 articles were searched (60 in Chinese and 53 in English),
      of which 12 were RCT. Three of the 12 articles were included for Meta analysis.
      Meta analysis showed that dextran-40 together with furosemide was effective for
      nephrotic edema. Human albumin solution could be used in nephrotic edema patients
      with coexistent severe hypoalbuminemia. A combination of diuretics by intravenous
      drip infusion was effective for diuretic-resistant nephrotic edema. CONCLUSIONS:
      The treatment for nephrotic edema should be individualized. The evidence of
      treatment of nephrotic edema has not been fully elucidated. Further multicentre,
      large sample, and randomized controlled trials are needed.

PMID- 17448311
TI  - [Mobilization effects of SCF along with G-CSF on bone marrow stem cells and
      endothelial progenitor cells in rats with unilateral ureteral obstruction].
AB  - OBJECTIVE: To study the mobilization effects of stem cell factor (SCF) along with
      granulocyte colony-stimulating factor (G-CSF) on bone marrow stem cells and
      endothelial progenitor cells in rats with unilateral ureteral obstruction (UUO).
      METHODS: Fifty-six healthy male Wistar rats were randomly divided into seven
      groups: control, SCF, G-CSF, SCF+G-SCF, Sham-operated, UUO and UUO+SCF+G-CSF
      groups (n=8 each). The rats from the control, SCF, G-CSF and SCF+G-CSF groups
      were hypodermically injected with normal saline (2 mL/kg), SCF (200 microg/kg), G
      CSF (200 microg/kg) and SCF along with G-CSF respectively for 5 days. The rats
      from the UUO and UUO+SCF+G-CSF groups were subjected to the ligation of right
      ureter and then were hypodermically injected with normal saline (2 mL/kg) and SCF
      (200 microg/kg)+G-CSF (200 microg/kg) respectively for 5 days. The sham-operated
      group had the same operative approach as the UUO and the UUO+SCF+G-CSF groups but
      the right ureter was not ligated. After operation they received a hypodermical
      injection of 2 mL/kg normal saline for 5 days. Five days later blood samples were
      collected. The percentages of CD34+ and CD34+/CD133+ cells in intravenous blood
      mononuclear cells were detected by flow cytometry. Serum contents of glutamate
      pyruvate transaminase (GPT), glutamic oxalacetic transaminase (GOT), urea
      nitrogen and creatinin were measured. RESULTS: Except for the sham-operated
      group, the other five groups (SCF, G-CSF, SCF+G-SCF, UUO and UUO+ SCF+G-CSF
      groups) had significantly higher percentage of CD34+ cells and CD34+/CD133+ cells
      in intravenous blood mononuclear cells than the control group (P < 0.05). There
      were significant differences in the percentage of CD34+ cells and CD34+/CD133+
      cells among the five groups (P < 0.05). The UUO+SCF+G-CSF group showed the
      highest percentage of CD34+ cells and CD34+/CD133+ cells, followed by the SCF+G
      CSF group. There were no significant differences in serum contents of GPT, urea
      nitrogen and creatinin among the seven groups. Except the UUO group showed higher
      GOT contents, there were no significant differences in the GOT contents among the
      other six groups. CONCLUSIONS: The mobilization effects of SCF and G-CSF on bone
      marrow stem cells and endothelial progenitor cells were not always in paraller. A
      combination of SCF and G-CSF can effectively mobilize stem cells and endothelial
      progenitor cells, and side effects were not found in the liver and the kidney.

PMID- 17448312
TI  - [Effect of hyperbillirubinemia of newborn on renal tubule function].

PMID- 17448313
TI  - [Clinical presentations and pathologic features of 25 cases of infant nephrotic
      syndrome].

PMID- 17448314
TI  - [Effect of Shenyankangfu tablet on urinary IL-6 and its therapeutic effect in
      children with Henoch-Schonlein purpura nephritis].

PMID- 17448315
TI  - Effect of dexamethasone on the content of pulmonary surfactant protein D in young
      rats with acute lung injury induced by lipopolysaccharide.
AB  - OBJECTIVE: Pulmonary surfactant protein-D (SP-D) is regarded as a valuable
      biomarker in acute lung injury (ALI) and acute respiratory distress syndrome
      (ARDS). This study was to explore the changes of SP-D content in lung tissue
      following ALI and the effect of dexamethasone (Dex) on the SP-D content in young
      rats. METHODS: One hundred and forty-four 21-day-old Sprague-Dawley rats were
      randomly assigned into control, ALI and Dex-treated groups. ALI was induced by
      intraperitoneal injection of lipopolysaccharide (LPS) (4 mg/kg) in the rats from
      the ALI and Dex-treated groups. Normal saline was given for the control group.
      Dex (5 mg/kg) was administered 1 hr after LPS injection in the Dex-treated group.
      At each time interval of 6, 12, 24, 36, 48 and 72 hrs after LPS injection, eight
      rats of each group were randomly chosen and sacrificed. Western blot was employed
      to detect the content of SP-D in lung tissues. RESULTS: The pulmonary SP-D
      content decreased significantly at 36, 48 and 72 hrs after LPS administration in
      the ALI group, and reduced to a nadir (0.92 +/-0.11 vs 3.27 +/- 0.52) at 48 hrs
      compared with that of the control group (P < 0.01). The SP-D content in the Dex
      treated group increased significantly at 36,48 and 72 hrs after LPS
      administration when compared with the ALI group (P < 0.01). A significant
      difference in the SP-D content between the Dex-treated and the control group was
      noted only at 72 hrs after LPS administration (P < 0.05). CONCLUSIONS: The SP-D
      content in lung tissue was reduced following ALI in young rats at the early
      stage. Early administration of Dex can significantly increase the pulmonary SP-D
      content.

PMID- 17448316
TI  - [Folic acid antagonist methotrexate causes the development malformation of heart
      and down-regulates the BMP2b and HAS2 expressions in zebrafish].
AB  - OBJECTIVE: To study the effect of methotrexate (MTX), a folic acid antagonist
      which can lead to folic acid deficient, on the cardiac development and on the
      expressions of BMP2b and HAS2 in zebrafish. METHODS: The zebrafish embryos at 6
      48 hrs post fertilization (hpf) were treated with various concentrations of MTX
      (0.5 x 10(-3), 1.0 x 10(-3) and 2.0 x 10(-3) M). At 48 hpf, the percentage of
      cardiac malformation and heart rate were recorded. The zebrafish embryos at 6-10
      hpf treated with 1.5 x 10(-3) M MTX were used as the MTX treatment group. At 24
      and 48 hpf the cardiac morphology was observed under a microscope. The
      expressions of BMP2b and HAS2 in zebrafish were detected by in situ antisense RNA
      hybridization and real-time PCR. RESULTS: 6-12 hpf, the early embryonic
      developmental stage, was a sensitive period that MTX affected cardiac formation
      of zebrafish. The retardant cardiac development and the evidently abnormal
      cardiac morphology was found in the MTX treatment group. The results of in situ
      antisense RNA hybridization showed that the expressions of BMP2b and HAS2 in the
      zebrafish heart were reduced in the MTX treatment group at 36 and 48 hpf. The
      real-time PCR results demonstrated that the BMP2b expression decreased at 12, 24,
      36 and 48 hpf, and that the HAS2 expression decreased at 24, 36 and 48 hpf in the
      treatment group compared with the control group without MTX treatment.
      CONCLUSIONS: The inhibition of folic acid function may affect cardiac development
      of early embryos, resulting in a retardant development and a morphological
      abnormality of the heart in zebrafish, possibly by down-regulating the
      expressions of BMP2b and HAS2.

PMID- 17448317
TI  - [Expression of bcl-2 protein and apoptosis of neurocytes in neonatal rats with
      brain white matter damage].
AB  - OBJECTIVE: Some research has shown that the brain white matter damage is closely
      related to apoptosis of pre-oligodendrocytes. The relationship of bcl-2 protein,
      a protein of anti-apoptosis, with brain white matter damage in neonatal rats is
      rarely reported. This study examined the changes of bcl-2 protein expression
      following brain white matter damage in neonatal rats. METHODS: Ninety 2-day-old
      Sprague-Dawley (SD) rats were randomly divided into 2 groups: experimental group
      (n=45) and control group (n=45). Brain white matter damage was induced by
      ligation of the right common artery, followed by 6% hypoxia exposure in the rats
      from the experimental group. The rats of the control group were sham-operated,
      without hypoxia-ischemia treatment. The expression of bcl-2 protein in the
      periventricular white matter and the callositas was detected by
      immunohistochemical technique. Apoptosis of neurocytes in these tissues was
      detected by TUNEL. RESULTS: The apoptosis index of neurocytes in the experimental
      group was up-regulated at 4, 12 and 24 hrs and at 3 and 7 days, peaking at 3 days
      after white matter damage, compared with the control group (P < 0.05). The
      expression of bcl-2 protein in the experimental group began to increase at 1 hr,
      reached a peak at 12 hrs and remained a higher level until 3 days after white
      matter damage compared with that observed in the control group (P < 0.05).
      CONCLUSIONS: The expression of bcl-2 protein increased at the early stage of
      white matter damage in neonatal rats. The peak of apoptosis lagged behind that of
      the bcl-2 protein expression, which suggests that bcl-2 protein may have
      protective effects against neuronal apoptosis.

PMID- 17448318
TI  - [Protection of captopril against chronic lung disease induced by hyperoxia in
      neonatal rats].
AB  - OBJECTIVE: This study examined the protein and mRNA contents of angiotesin
      converting enzyme (ACE), angiotensin II (Ang II) and type I collagen and the
      changes of lung histomorphology in neonatal rats with hyperoxia-induced chronic
      lung disease (CLD) and investigated the protection of captopril against CLD and
      the possible mechanism. METHODS: A total of 240 term neonatal Wistar rats were
      randomly assigned into air, model, normal saline and captopril-treated groups
      (n=60 each). The air group was exposed to room air (FiO2=0.21) immediately after
      birth. The other three groups were exposed to hyperoxia (FiO2=0.9) for 21 days to
      induce lung injury. The captopril-treated group received captopril daily (30
      mg/kg) by intragastric administration between the 7th and 21st days of hyperoxia
      exposure. The normal saline group was administrated with normal saline instead.
      At each time interval of 1, 3, 7, 14 and 21 days after experiment, six rats of
      each group were randomly chosen and sacrificed. The protein and mRNA levels of
      ACE, Ang II and type I collagen were measured by enzyme-linked
      immunosorbentassay, radio-immunity technique and RT-PCR. The changes of lung
      histomorphology were observed under a light microscope. RESULTS: The protein and
      mRNA expressions of ACE, Ang II and type I collagen increased significantly in
      the model and normal saline groups on the 14th and peaked on the 21st days of
      exposure compared with those of the air group (P < 0.05 or 0.01). Captopril
      treatment reduced significantly the protein and mRNA expressions of ACE, Ang II
      and type I collagen compared the model and normal saline groups on the 14th and
      21st days, although the values were significantly higher than the air group (P <
      0.05 ). The histopathologic examination demonstrated broadened lung interstitium
      and reduced alveolar quantity and lung fibrosis was developed in the model and
      normal saline groups on the 14th day of exposure. Captopril treatment obviously
      alleviated the changes of lung histomorphology. CONCLUSIONS: Captopril can
      inhibit the protein and mRNA expressions of ACE, Ang II and type I collagen and
      alleviate lung fibrosis in neonatal rats with hyperoxia-induced lung injury/CLD.
      This may contribute to one of the possible mechanisms underlying the protective
      effects of captopril against lung injury/CLD.

PMID- 17448319
TI  - [Hyperoxia-induced retinal peroxidative injury in immature rats].
AB  - OBJECTIVE: To investigate the role of oxidative stress in the pathogenesis of
      retinal injury induced by hyperoxia. METHODS: Sixty immature Sprague-Dawley (SD)
      rats born at a gestational age of 21 days, were randomly exposed to room air (air
      group, n=30) or 95% oxygen (hyperoxia group, n=30) immediately after birth.
      Plasma 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) levels were determined by
      ELISA. The ultrastructures of the retina were observed under a transmission
      electron microscope. RESULTS: The plasma 8-iso-PGF2alpha contents of the air
      group were 19.09 +/-5.57, 18.24+/-5.91 and 17.00 +/- 5.58 pg/mL on the 3rd, 7th
      and 14th days after birth, respectively (F=1.024, P> 0.05). The plasma 8-iso-PGF2
      contents in the hyperoxia group on the 3rd (28.33 +/- 5.59 pg/mL), the 7th day
      (51.20 +/- 15.01 pg/mL) and 14th day (84.54 +/- 14.85 pg/mL) after birth were
      significantly higher than those of the air group (t=2.863, P< 0.05; t=5.073, P<
      0.01; t=11.006, P< 0.01). Moreover, the plasma 8-iso-PGF2 contents in the
      hyperoxia group increased with the prolonged hyperoxia exposure (F=150.7, P <
      0.01). The ultrastructures of retina in the air group were normal. Hyperoxia
      exposure resulted in abnormalities of the ultrastructures of retina, manifesting
      as the membrane discs rarefied, twisted and disrupted and mitochondrial swelling.
      CONCLUSIONS: Oxidative stress can results in retinal injury in immature rats. An
      increased plasma level of 8-iso-PGF2alpha is related to the injury degree of
      retina.

PMID- 17448320
TI  - [A case report of spinocerebellar ataxia].

PMID- 17448321
TI  - [Research progress on hospice care for pediatric patients].

PMID- 17448322
TI  - Asthma and autoimmunity: is there a connection?

PMID- 17448326
TI  - Allergic reactions to foods by inhalation.
AB  - Although allergic reactions to foods occur most commonly after ingestion,
      inhalation of foods can also be an underlying cause of these reactions. For
      example, published reports have highlighted the inhalation of allergens from
      fish, shellfish, seeds, soybeans, cereal grains, hen's egg, cow's milk, and many
      other foods in allergic reactions. Symptoms have typically included respiratory
      manifestations such as rhinoconjunctivitis, coughing, wheezing, dyspnea, and
      asthma. In some cases, anaphylaxis has been observed. In addition, there have
      been many investigations of occupational asthma following the inhalation of
      relevant food allergens. This report reviews the current literature focusing on
      allergic reactions to foods by inhalation.

PMID- 17448327
TI  - The natural history of peanut and tree nut allergy.
AB  - Peanut and tree nut allergies were once thought to be permanent. Recent studies
      have shown that about 20% and 10%, respectively, of young patients may outgrow
      peanut and tree nut allergies. For the majority of patients, however, the natural
      history is not favorable. In addition, approximately 8% of patients who outgrow
      peanut allergy may suffer a recurrence. The rising prevalence of these allergies,
      coupled with the knowledge that allergic reactions to these foods have the
      potential to be severe or fatal and that accidental exposures are common, makes
      developing effective treatments to alter the natural history of peanut and tree
      nut allergies even more crucial for those who will not outgrow them. At this
      time, avoidance of the offending foods and being prepared to treat a potential
      reaction after accidental ingestion is the only treatment, but many promising
      therapeutic interventions are being investigated.

PMID- 17448328
TI  - Risk factors for the development of food allergy.
AB  - Both genetic and environmental factors seem to predispose to the development of
      food allergy. A most notable factor is diet, particularly during infancy.
      Possible other factors include maternal diet during pregnancy and lactation,
      birth by cesarean section, exposure to tobacco smoke, multivitamin
      supplementation, and intake of antacids. It is important to identify and control
      such risk factors to reduce the development of food allergy.

PMID- 17448329
TI  - Managing children with food allergies in childcare and school.
AB  - In the past decade the rise in life-threatening allergic reactions to foods in
      young children has necessitated increased interaction among personnel in the
      psychosocial, medical, and educational arenas regarding the multifaceted aspects
      of this concerning problem. Schools and childcare facilities are vital venues for
      the continued growth and development of children outside the home. However, these
      facilities offer unique challenges to caring for the food-allergic child,
      requiring that the medical, educational, and caretaking communities work in
      unison to provide the safest environment for all children. Despite the potential
      obstacles, these settings offer a tremendous opportunity for the development and
      implementation of strategies to provide for proper identification of children at
      risk, to increase awareness and prevention, and for the provision of optimal
      treatment of food-related anaphylactic reactions occurring outside the home.

PMID- 17448331
TI  - Laryngopharyngeal reflux and chronic sinusitis.
AB  - In patients with chronic and recurrent sinusitis, laryngopharyngeal reflux
      disease may play a significant role. Laryngopharyngeal reflux disease differs
      from gastroesophageal reflux disease in the extent of reflux (into the
      hypopharynx and above) as well as timing (occurring more often when the patient
      is upright). Most patients are unaware of the extent of their symptoms, and
      diagnostic tools such as pH probe, multichannel intraluminal impedance, and
      manometry are required for adequate diagnosis. Although therapy with lifestyle
      modification and acid-suppressive agents may improve reflux in the majority of
      patients, for many with persistent symptoms, endoscopic or surgical intervention
      is required to reduce reflux successfully.

PMID- 17448332
TI  - Inflammatory mechanisms and remodeling in chronic rhinosinusitis and nasal
      polyps.
AB  - Chronic rhinosinusitis (CRS) is presently classified into two subgroups: CRS
      without and CRS with nasal polyps. A variety of inflammatory mediators, including
      cytokines and chemokines, as well as adhesion molecules and matrix
      metalloproteinases, are upregulated in both subgroups of CRS; remodeling is also
      observed in both. However, there are also characteristic differences. Whereas CRS
      without nasal polyps has more neutrophilic infiltration, in CRS with nasal polyps
      (especially when associated with allergy/asthma) eosinophil infiltration is
      strikingly increased. Although several features of remodeling (eg, squamous
      metaplasia, basement membrane thickening, collagen deposition, hyperplasia of
      mucous glands, and goblet cells) are features seen in both subgroups of CRS,
      epithelial shedding as observed in asthma is not seen in either subgroup.
      Furthermore, pseudocyst formation seen in CRS with nasal polyps is not seen in
      CRS without nasal polyps.

PMID- 17448333
TI  - The role of antileukotriene drugs in management of rhinitis and rhinosinusitis.
AB  - Antileukotriene drugs have been studied for more than 15 years. In this review we
      examine the role of leukotrienes in rhinitis and rhinosinusitis, and explore the
      clinical literature supporting the use of anti-leukotriene agents in these
      diseases. Although these medications clearly are efficacious in rhinitis, it is
      unclear where in the armamentarium they should be used. The evidence for use in
      sinusitis has not been well studied except in sinusitis-associated aspirin
      exacerbated respiratory disease. In this circumstance there is information that
      allows use of antileukotriene agents to be considered efficacious. We provide our
      rationale for use and await future clinical studies to answer this important
      question.

PMID- 17448334
TI  - Progress in surgical management of chronic rhinosinusitis and nasal polyposis.
AB  - Endoscopic sinus surgery (ESS) remains the treatment of choice for medically
      refractory chronic rhinosinusitis (CRS) with or without nasal polyposis (NP). ESS
      has undergone review, reassessment, and substantial refinement. Several advances
      (eg, powered instrumentation, image guidance, adjunctive intraoperative
      procedures) have expanded the scope of cases amenable to ESS, decreased operative
      time and intraoperative blood loss, and improved safety. Procoagulant nasal/sinus
      packing and refinements of technique have decreased the need for postoperative
      removal of packing, thus decreasing morbidity. Methods to reduce synechia
      formation (ie, mitomycin-c) have been explored, with mixed results. Novel methods
      of sinusotomy (eg, balloon catheter dilatation of the sinus ostia) have had
      limited but interesting short-term results. We can expect further advances in ESS
      with better patient outcomes. However, continued elucidation of the underlying
      pathophysiology of CRS and NP are essential to long-term improvement.

PMID- 17448335
TI  - The potential of Mycobacterium to protect against allergy and asthma.
AB  - The increase in the global incidence of atopic disease and asthma during the past
      few decades has been ascribed to environmental factors, including the reduction
      in exposure to serious infections. The hypothetical framework to explain the
      inverse relationship between infections and atopic disease and asthma has been
      called the "hygiene hypothesis." Animal and experimental models have identified
      Mycobacteria as important potential candidates in the hygiene hypothesis by
      demonstrating that exposure to Mycobacteria or mycobacterial proteins led to
      subsequent reduction in different atopic manifestations. Although there are
      epidemiological studies in support, they have not always been consistent. In this
      review we appraise epidemiologic evidence on the inverse relationship between
      mycobacterial exposure and atopic disease, explore the immunological mechanisms
      involved and evidence that this effect may be dose-dependent, and discuss the
      challenges facing the use of Mycobacteria as vaccine for prevention of atopic
      disease.

PMID- 17448336
TI  - Building better mouse models of asthma.
AB  - Allergic asthma is a complex disease that has been modeled extensively in small
      rodents. Airway eosinophilia and changes in lung function have been documented
      using a variety of protocols. However, recent efforts have improved these models
      by trying to replicate the structural remodeling that occurs in the lung as a
      consequence of chronic allergen-driven inflammation. This review documents the
      recent developments in protocols and systems designed to examine pathways leading
      to allergen-induced airway remodeling.

PMID- 17448337
TI  - Fast and sensitive trace analysis of malachite green using a surface-enhanced
      Raman microfluidic sensor.
AB  - A rapid and highly sensitive trace analysis technique for determining malachite
      green (MG) in a polydimethylsiloxane (PDMS) microfluidic sensor was investigated
      using surface-enhanced Raman spectroscopy (SERS). A zigzag-shaped PDMS
      microfluidic channel was fabricated for efficient mixing between MG analytes and
      aggregated silver colloids. Under the optimal condition of flow velocity, MG
      molecules were effectively adsorbed onto silver nanoparticles while flowing along
      the upper and lower zigzag-shaped PDMS channel. A quantitative analysis of MG was
      performed based on the measured peak height at 1615 cm(-1) in its SERS spectrum.
      The limit of detection, using the SERS microfluidic sensor, was found to be below
      the 1-2 ppb level and this low detection limit is comparable to the result of the
      LC-Mass detection method. In the present study, we introduce a new conceptual
      detection technology, using a SERS microfluidic sensor, for the highly sensitive
      trace analysis of MG in water.

PMID- 17448338
TI  - Autocorrelation infrared analysis of mineralogical samples: the influence of user
      controllable experimental parameters.
AB  - Autocorrelation infrared (ACIR) analysis is based upon the application of the
      autocorrelation function corr(alpha,omega') = integral(-infinity)(infinity)
      alpha(omega + omega') alpha(omega) d omega to standard Fourier transform infrared
      (FTIR) transmission spectra. We present a rigorous examination of the effect of
      experimental parameters such as dilution ratio, spectral resolution, grinding
      time and pressing conditions upon the ACIR analysis of haematite. Results were
      found to vary by less than 4.5% irrespective of sample preparation, instrumental
      and data collection parameters. For a series of perovskite samples, the
      relationship between the measured effective linewidth and material composition
      appears to be reproducible, even though the absolute magnitudes of delta corr
      values do not. Our results further indicate that the ACIR technique is indeed
      valid for comparative analysis of synthetic sample sequences that vary slightly
      in composition or structural state, provided that primary spectra are all
      recorded by the same instrument.

PMID- 17448339
TI  - Flow injection analysis of imidacloprid in natural waters and agricultural
      matrixes by photochemical dissociation, chemical reduction, and nitric oxide
      chemiluminescence detection.
AB  - A flow injection analysis (FIA) to quantify imidacloprid was developed based upon
      (1) ultraviolet (254 nm) photochemical dissociation of imidacloprid to produce
      nitrite, (2) chemical reduction of the nitrite to nitric oxide by iodide in acid,
      (3) removal of gas-phase nitric oxide from the aqueous stream using a membrane
      separator, and (4) detection of the nitric oxide by chemiluminescent reaction
      with ozone. The cross-reactivity of imidacloprid with eight metabolites of
      imidacloprid was determined using a commercial ELISA kit and the FIA method.
      While the ELISA kit demonstrated varying degrees of cross-reactivity, cross
      reactivity in the FIA method was observed for only the N-nitro and N-nitroso
      metabolites. The optimized analytical FIA method, FIA provides a linear response
      in imidacloprid concentration over four orders of magnitude, has a limit of
      detection of 5.6 pmol (1.5 ng) of imidacloprid, and exhibits an inter-day
      precision of 0.4%. Spike-recoveries by FIA demonstrated excellent recovery of
      imidacloprid in natural waters, hemlock xylem fluid, honey, and grapes with
      little to no interference from the matrix.

PMID- 17448340
TI  - Enhancement in sample preconcentration by the on-line incorporation of cloud
      point extraction to flow injection analysis inside the chemiluminescence cell and
      the determination of total serum bilirubin.
AB  - The on-line incorporation of cloud point extraction (CPE) to flow injection
      analysis (FIA) was previously based on the use of a cotton-packed column to
      entrap the analyte-containing surfactant aggregates after salt-induced CPE, and
      then the preconcentrated analyte was eluted into a separate detection cell for
      subsequent chemiluminescence (CL) detection (via the peroxyoxalate CL reaction).
      In the work, the on-line CPE/FIA technique was improved by the following: (1)
      sample preconcentration and CL detection were both carried out directly inside
      the collection column, thus avoiding the decrease in detection sensitivity due to
      sample dispersion and dilution, and (2) CL detection was performed through the
      reaction between nitrite and hydrogen peroxide, which is compatible with aqueous
      samples and should allow for chemical excitation to occur more efficiently inside
      the collection column. In addition to more effective sample preconcentration, the
      CL detection of the entrapped analytes directly inside the collection column,
      i.e., a unique heterogeneous microenvironment in which analyte-containing
      surfactant aggregates were embedded within the densely packed filtering material,
      may also contribute to the overall increase in CL intensity (e.g., a CL
      enhancement factor of ca. 1000). Under optimum experimental conditions, the
      calibration curve was found to be linear for the CL detection of bilirubin (5 to
      120 microg L(-1)), the limit of detection (S/N = 3) was 1.8 microg L(-1), and the
      R.S.D. was ca. 2.6% (n = 30) for 20 microg L(-1) bilirubin. Good agreements were
      obtained for the determination of total bilirubin in certified reference human
      serum samples between the present approach and an established clinical method.

PMID- 17448341
TI  - Cloud point extraction applied to casein proteins of cow milk and their
      identification by mass spectrometry.
AB  - This work describes the optimization of a cloud point extraction (CPE) method for
      casein proteins from cow milk samples. To promote phase separation,
      polyoxyethylene(8) isooctylphenyl ether (Triton X-114) and sodium chloride (NaCl)
      were used as nonionic surfactant and electrolyte, respectively. Using
      multivariate studies, four major CPE variables were evaluated: Triton X-114
      concentration, sample volume, NaCl concentration, and pH. The results show that
      surfactant concentration and sample volume were the main variable affecting the
      CPE process, with the following optimized parameters: 1% (w/v) Triton X-114
      concentration, 50 microL of sample volume, 6% (w/v) NaCl concentration and
      extractions carried out at pH 7.0. At these conditions, 923+/-66 and 67+/-2
      microg mL(-1) of total protein were found in the surfactant-rich and surfactant
      poor phases, respectively. Finally, matrix-assisted laser desorption ionization
      time of flight mass spectrometry (MALDI-TOF MS) was then used to evaluate those
      target proteins (alpha(s1)-casein, alpha(s2)-casein and beta-casein) separation
      as well as to check the efficiency of the extraction procedure, making a
      fingerprint of those target proteins possible.

PMID- 17448342
TI  - Analysis of brain distribution and biliary excretion of a nutrient supplement,
      gastrodin, in rat.
AB  - Gastrodin is a bioactive constituent of rhizome in Gastrodia elata Blume
      (Orchidaceae) The aim of this study is to develop a rapid and sensitive liquid
      chromatographic method coupled to microdialysis sampling system to measure the
      unbound of gastrodin in rat blood, brain and bile. Microdialysis probes were
      simultaneously inserted into the jugular vein, brain striatum and bile duct of
      each anesthetized rat for sampling after the administration of gastrodin (100 or
      300 mg kg(-1)) through the femoral vein. Separation of unbound gastrodin from
      various biological fluids was applied to an RP-select B column (250 mm x 4.6 mm
      i.d., 5 microm). The mobile phase consisted of acetonitrile-50 mM potassium
      dihydrogen phosphate buffer-triethylamine (5:95:0.1, v/v/v, adjusted to pH 2.5
      with orthophosphoric acid) with a flow rate of 1 mL min(-1). The UV detector
      wavelength was set at 221 nm. Fifteen minutes after the administration, the
      gastrodin reached the peak concentration in brain and bile. In addition, the
      results indicate that gastrodin penetrates the blood-brain barrier (BBB) and goes
      through hepatobiliary excretion.

PMID- 17448343
TI  - Simultaneous determination of citrus limonoid aglycones and glucosides by high
      performance liquid chromatography.
AB  - High performance liquid chromatography (HPLC) method has been developed for
      simultaneous quantification of limonoid aglycones and glucosides on a reversed
      phase C18 column using a binary solvent system, coupled with diode array
      detector. Seven limonoids such as limonin, nomilin, isolimonic acid, ichangin,
      isoobacunoic acid, limonin 17-beta-D glucopyranoside and deacetyl nomilinic acid
      17-beta-D glucopyranoside were separated and detected at 210 nm. Furthermore,
      limonoids were separated, identified and quantified in four varieties of citrus
      fruits and seeds using developed method. Limonin and limonin glucoside were found
      to be the predominant limonoid aglycone and glucoside, respectively, in all
      tested samples. The sensitivity of the method was found to be 0.25-0.50 microg
      for tested limonoids.

PMID- 17448344
TI  - Extraction and determination of papaverin in pericarpium papaveris using aqueous
      two-phase system of poly(ethylene glycol)-(NH4)2SO4 coupled with high-performance
      liquid chromatography.
AB  - Based on aqueous two-phase system (ATPS) of poly(ethylene glycol) (PEG)
      (NH4)2SO4, a simple pretreatment approach was developed for the extraction and
      determination of papaverin in pericarpium papaveris. The influence factors on
      phase behavior of the ATPS and partition behavior of papaverin was investigated,
      and partition mechanism based on the hydrophobic interaction between PEG and
      analyte molecules was proposed. Under the optimal conditions, the extraction
      efficiencies for papaverin were 93-96%, and the recoveries of the added standard
      were 97-106% with relative standard deviations of 1.8-2.5%. Combined with a high
      performance liquid chromatography (HPLC) method, this extraction technique has
      been successfully applied to the determination of papaverin in pericarpium
      papaveris with the detection limit of 2 ng mL(-1) and the linear range of 0.10-10
      microg mL(-1). Compared with the conventional liquid-liquid extraction or solid
      phase extraction, this method was more environmentally benign, more cost
      effective and much simpler due to the direct injection of the upper phase into
      HPLC system.

PMID- 17448345
TI  - Comparative validation of amisulpride determination in pharmaceuticals by several
      chromatographic, electrophoretic and spectrophotometric methods.
AB  - Nine accurate methods for determination of amisulpride in tablets: reversed phase
      high pressure liquid chromatography (RP-HPLC), aqueous capillary electrophoresis
      (CE), non-aqueous CE, normal phase (NP) and reversed-phase (RP) high performance
      thin layer chromatography (HPTLC) with densitometry and videodensitometry, and
      direct and derivative UV spectrophotometry were developed and validated. The HPLC
      was carried out using Nova-Pak C8 column and mobile phase consisted of
      acetonitrile-methanol-phosphate buffer pH 4.50 (15:5:80, v/v/v) with flow rate 1
      mL min(-1) and UV detection at 225 nm. The moclobemide was used as the internal
      standard. CE was performed using 75 microm x 82 cm fused silica capillary (65 cm
      effective), the internal standard was quetiapine. Detection was carried out at
      225 nm. For aqueous analysis, the 30 mM phosphate buffer pH 6.00, 30 kV voltage
      and 30 degrees C temperature were chosen, non-aqueous determination was performed
      with ammonia acetate 1 mM in acetonitrile-methanol (1:1, v/v), 30 kV voltage and
      25 degrees C temperature. NP-HPTLC was carried out using HPTLC silica F254
      plates, developed with hexane-ethanol-propylamine (5:5:0.1, v/v/v) through 9 cm
      distance. RP-HPTLC was developed with HPTLC RP8F254 plates, with mobile phase of
      tetrahydrofuran-phosphate buffer pH 3.50 (4:6, v/v), distance 4.5 cm. Both
      analyses were performed in horizontal chambers and scanned with densitometer at
      275 nm or videodensitometer at 254 nm. UV spectrophotometry was carried out in
      methanol, using 224 nm for direct assay and 258 nm (D1) for derivative assay. The
      precision and accuracy of all the methods were complexively compared. The highest
      accuracy was observed in RP-HPTLC, the highest precision was achieved in non
      aqueous CE method. The differences were not significant, so all the elaborated
      methods can be used in routine analysis.

PMID- 17448346
TI  - Influence of electronic and steric effects on stability constants and
      electrochemical reversibility of divalent ion complexes with glycine and
      sarcosine. A glass electrode potentiometric, sampled direct current
      polarographic, virtual potentiometric, and molecular modelling study.
AB  - Cd(II) complexes with glycine (gly) and sarcosine (sar) were studied by glass
      electrode potentiometry, direct current polarography, virtual potentiometry, and
      molecular modelling. The electrochemically reversible Cd(II)-glycine-OH labile
      system was best described by a model consisting of M(HL), ML, ML2, ML3, ML(OH)
      and ML2(OH) (M = Cd(II), L = gly) with the overall stability constants, as log
      beta, determined to be 10.30+/-0.05, 4.21+/-0.03, 7.30+/-0.05, 9.84+/-0.04, 8.9+/
      0.1, and 10.75+/-0.10, respectively. In case of the electrochemically quasi
      reversible Cd(II)-sarcosine-OH labile system, only ML, ML2 and ML3 (M = Cd(II), L
      = sar) were found and their stability constants, as log beta, were determined to
      be 3.80+/-0.03, 6.91+/-0.07, and 8.9+/-0.4, respectively. Stability constants for
      the ML complexes, the prime focus of this work, were thus established with an
      uncertainty smaller than 0.05 log units. The observed departure from
      electrochemical reversibility for the Cd-sarcosine-OH system was attributed
      mainly to the decrease in the transfer coefficient alpha. The MM2 force field,
      supplemented by additional parameters, reproduced the reported crystal structures
      of diaqua-bis(glycinato-O,N)nickel(II) and fac-tri(glycinato)-nickelate(II) very
      well. These parameters were used to predict structures of all possible isomers of
      (i) [Ni(H2O)4(gly)]+ and [Ni(H2O)4(sar)]+; and (ii) [Ni(H2O)3(IDA)] and
      [Ni(H2O)3(MIDA)] (IDA = iminodiacetic acid, MIDA = N-methyl iminodiacetic acid)
      by molecular mechanics/simulated annealing methods. The change in strain energy,
      deltaU(str), that accompanies the substitution of one ligand by another (ML + L' 
      -> ML' + L), was computed and a strain energy deltaU(str) = +0.28 kcal mol(-1)
      for the reaction [Ni(H2O)4(gly)]+ + sar --> [Ni(H2O)4(sar)]+ + gly was found.
      This predicts the monoglycine complex to be marginally more stable. By contrast,
      for the reaction [Ni(H2O)3IDA] + MIDA --> [Ni(H2O)3MIDA] + IDA, deltaU(str) = 
      0.64 kcal mol(-1), and the monoMIDA complex is predicted to be more stable. This
      correlates well with (i) stability constants for Cd-gly and Cd-sar reported here;
      and (ii) known stability constants of ML complex for glycine, sarcosine, IDA, and
      MIDA.

PMID- 17448347
TI  - Micellar effect on the sensitivity of spectrophotometric Mo(VI) determination
      based on the formation of gallic acid complex providing evidence for the
      polyoxoanion structure of molybdate ions.
AB  - In this study effects of anionic (sodium dodecyl sulfate, SDS), cationic
      (cetyltrimethylammonium bromide, CTAB) and nonionic (Triton X-100, TX100)
      micelles on the sensitivity of spectrophotometric molybdenum(VI) (Mo)
      determination based on the formation of a binary complex with gallic acid (GA)
      were investigated. Micellar CTAB was found to enhance the formation of Mo-GA
      complex. SDS micelles exerted an inhibitory effect while TX100 micelles had no
      effect on the complex formation. By the optimization of experimental conditions,
      the determination limit of the method suggested in the literature was lowered
      from 5.2x10(-5) to 4.6x10(-6) and to 5.7x10(-7) M, in the absence and presence of
      CTAB, respectively. The mechanism of the effect of CTAB was investigated by
      spectrophotometric titrations and it was concluded that CTAB did not form a
      ternary complex with Mo and GA. The stoichiometry of the complex, deduced from
      the results of spectrophotometric titrations, provided evidence for the formation
      of para-Mo7O4(6-) polyanions at pH 4.5, indicating to the formation of a charge
      transfer complex between these ions and GA in micellar medium.

PMID- 17448348
TI  - Novel indirect enzyme-linked immunosorbent assay (ELISA) method to detect Total
      E. coli in water environment.
AB  - In order to establish ELISA (enzyme-linked immunosorbent assay) method to detect
      Total E. coli in water environment, E. coli multi-characters antigens in water
      environment were prepared according to the characters of kinds of E. coli
      serotypes, including antigen of whole cell, antigen of disrupted whole cell,
      somatic antigen, flagellar antigen and fimbrial antigen. Total E. coli polyclonal
      antibodies were obtained from the New Zealand rabbits immunized with these five
      antigens, respectively. Antibodies generated in this research are with high
      titers and good purity, can conjugate with antigens, specifically, stably and
      strongly. Indirect ELISA shows the titers of antibody of whole cell and antibody
      of disrupted whole cell are both over 1x10(5). The cross-reactivity of the
      antibody is from 12 to 30% which indicate the specificity of the antibody against
      Total E. coli. Based on these antibodies, we established indirect ELISA method to
      detect Total E. coli in water environment. The matrix effects were studied and
      the results show that there is no significant influence by all the factors. The
      ELISA result shows that the detection limitation could be 10(4) CFU (colony
      forming units) L(-1). The indirect ELISA method developed in this study is well
      suited for Total E. coli analysis in real water samples as a rapid screen method.

PMID- 17448349
TI  - First approach to radionuclide mixtures quantification by using plastic
      scintillators. Influence of the diameter of the plastic beads.
AB  - Recent studies have evaluated the capability of plastic scintillation (PS) as an
      alternative to liquid scintillation (LS) in radionuclide activity determination
      without mixed waste production. In order to complete the comparison, we now
      assess the extent to which PS can be used to quantify mixtures of radionuclides
      and the influence of the diameter of the plastic scintillation beads in detection
      efficiency. The results show that the detection efficiency decreases and the
      spectrum shrink to lower energies when the size of the plastic scintillation
      beads increases, and that the lower the energy of the beta particle, the greater
      the variation takes place. Similar behaviour has been observed for beta-gamma and
      alpha emitters. Two scenarios for the quantification of mixtures are considered,
      one including two radionuclides (14C and 60Co) whose spectra do not overlap
      significantly, and the other including two radionuclides (137Cs and 90Sr/90Y),
      where the spectra of one the isotopes is totally overlapped by the other The
      calculation has been performed by using the conventional window selection
      procedure and a new approach in which the selected windows correspond to those
      with lower quantification errors. Relative errors obtained using the proposed
      approach (less than 10%) are lower than those of the conventional procedure, even
      when a radionuclide is completely overlapped, except for those samples with
      extreme activity ratios that were not included in the window optimization
      process.

PMID- 17448350
TI  - Speciation analysis of arsenic and selenium compounds in environmental and
      biological samples by ion chromatography-inductively coupled plasma dynamic
      reaction cell mass spectrometer.
AB  - An inductively coupled plasma mass spectrometer (ICP-MS) was used as an ion
      chromatographic (IC) detector for the speciation analysis of arsenic and
      selenium. The arsenic and selenium species studied included arsenite [As(III)],
      arsenate [As(V)], monomethylarsonic acid (MMA), dimethylarsinic acid (DMA),
      arsenobetaine (AsB), selenite [Se(IV)] and selenate [Se(VI)]. Gradient elution
      using (NH4)2CO3 and methanol at pH 9 allowed the chromatographic separation of
      all species in less than 12 min. Effluents from the IC column were delivered to
      the nebulization system of ICP-DRC-MS for the determination of arsenic and
      selenium. The potentially interfering 38Ar 40Ar+ and 40Ar 40Ar+ at the selenium
      masses m/z 78 and 80 were reduced in intensity by approximately 3 orders of
      magnitude by using 0.6 mL min(-1) CH4 as reactive cell gas in the DRC while an
      Rpq value of 0.3 was used. Meanwhile, arsenic was determined as the adduct ion
      75As 12CHH+ at m/z 89, which is more sensitive than 75As. The limits of detection
      for arsenic and selenium were in the range of 0.002-0.01 ng mL(-1) and 0.01-0.02
      ng mL(-1), respectively, based on peak height. The relative standard deviation of
      the peak areas for five injections of 5 ng mL(-1) As and Se mixture was in the
      range of 2-4%. The concentrations of arsenic and selenium species have been
      determined in urine samples collected locally. The major As and Se species in
      urines were AsB, DMA and probably selenosugar at concentration of 20-40, 15-19
      and 17-31 ng mL(-1), respectively. The recoveries were in the range of 94-105%
      for all the determinations. This method has also been applied to determine
      various arsenic compounds in two fish samples. In this study, a simple and rapid
      microwave-assisted extraction method was used for the extraction of arsenic
      compounds from fish. The arsenic species were quantitatively leached with an 80%
      v/v methanol solution in a focused microwave field during a period of 5 min.

PMID- 17448351
TI  - Time measurement-visual analysis of nickel(II) using autocatalytic reaction with
      sodium sulfite/hydrogen peroxide system and its application to the length
      detection-flow analysis.
AB  - Trace amounts of nickel(II) can function as a trigger (= reaction initiator) in
      an autocatalytic reaction with the sodium sulfite/hydrogen peroxide system. Based
      on this finding, sub-microg L(-1) levels of nickel(II) were determined by a time
      measurement using the autocatalytic reaction. The detection range using the above
      method was 10(-9)-10(-5) M, the detection limit (3sigma) was 8.1x10(-10) M (0.047
      microg L(-1)), and the relative standard deviation was 2.66% at nickel(II)
      concentration of 10(-7) M (n = 7). This method was applied to length detection
      flow injection analysis. The detection range for the flow injection analysis was
      2x10(-9)-2x10(-3) M. The detection limit (3sigma) was 1.4x10(-9) M (0.082 microg
      L(-1)), and the relative standard deviation was 1.86 at initial nickel(II)
      concentration of 10(-6) M (n = 7).

PMID- 17448352
TI  - Kinetic spectrophotometric method for rapid determination of trace formaldehyde
      in foods.
AB  - A simple and sensitive kinetic-spectrophotometric method was developed for the
      determination of ultra trace amount of formaldehyde in food samples. The method
      was based on the oxidation of rhodamine B (RhB) by potassium bromate in sulfuric
      acid medium (formaldehyde as catalyst). The reaction was monitored by measuring
      the decrease in absorbance of the dye at 515 nm after 6 min. The developed method
      allowed the determination of formaldehyde in the range of 10-100 microg L(-1)
      with good precision, accuracy and the detection limit was down to 2.90 microg L(
      1). The relative standard deviations for the determination of 10 and 60 microg L(
      1) of formaldehyde were 3.0% and 1.9% (n = 10), respectively. The method was
      found to be sensitive, selective and was applied to the determination of
      formaldehyde in foods with satisfactory results.

PMID- 17448357
TI  - Climate change and children.
AB  - Climate change is increasing the burden of climate-sensitive health determinants
      and outcomes worldwide. Acting through increasing temperature, changes in the
      hydrologic cycle, and sea level rise, climate change is projected to increase the
      frequency and intensity of heat events and extreme events (floods and droughts),
      change the geographic range and incidence of climate-sensitive vector-, food-,
      and waterborne diseases, and increase diseases associated with air pollution and
      aeroallergens. Children are particularly vulnerable to these health outcomes
      because of their potentially greater exposures, greater sensitivity to certain
      exposures, and their dependence on caregivers.

PMID- 17448358
TI  - Protecting children from toxic exposure: three strategies.
AB  - To a toxicologist, "poisonings" are cases in which the child has a defined
      pattern of symptoms, corresponding to toxic effects at a mid to high level of
      exposure. "Toxicity" refers to a broader spectrum of effects. At lower levels of
      toxicity a child may have no specific, individual symptoms but may be affected
      subclinically. There are three basic strategies to protect children: individual
      intervention, the preventive medicine strategy, and the public health strategy.
      This article uses lead exposure as a model for discussing these differences in
      terminology and the three different protective strategies.

PMID- 17448359
TI  - Mercury exposure and public health.
AB  - Mercury is a metal that is a liquid at room temperature. Mercury has a long and
      interesting history deriving from its use in medicine and industry, with the
      resultant toxicity produced. In high enough doses, all forms of mercury can
      produce toxicity. The most devastating tragedies related to mercury toxicity in
      recent history include Minamata Bay and Niagata, Japan in the 1950s, and Iraq in
      the 1970s. More recent mercury toxicity issues include the extreme toxicity of
      the dimethylmercury compound noted in 1998, the possible toxicity related to
      dental amalgams, and the disproved relationship between vaccines and autism
      related to the presence of the mercury-containing preservative, thimerosal.

PMID- 17448360
TI  - Update on the clinical management of childhood lead poisoning.
AB  - Childhood lead poisoning is still an enormous public health issue in the United
      States, affecting thousands of children and their families. New evidence suggests
      that even very low blood lead levels, less than 10 microg/dL, can be associated
      with neurologic injury. This article discusses characteristics of children at
      high risk for lead poisoning, unusual sources of lead contamination, and new
      aspects of lead's pathophysiology. It includes current thinking on the clinical
      management and prevention of childhood lead poisoning.

PMID- 17448361
TI  - Environments, indoor air quality, and children.
AB  - This article addresses air-quality science in the indoor environments in which
      children and adolescents find themselves, including the home, the school, and
      other environments such as work and recreational situations. The home arena is
      covered extensively, presenting an analysis of the usual exposures such as
      environmental tobacco smoke and bioaerosols and also touching on discrete issues
      such as sudden infant death syndrome, carbon monoxide, and public housing.
      Recreation and work environments are covered as well.

PMID- 17448362
TI  - Health effects of mold in children.
AB  - Mold is ubiquitous, and exposure to mold and its products of metabolism is
      unavoidable, whether indoors or outdoors. Mold can produce a variety of adverse
      health outcomes by four scientifically validated pathophysiologic mechanisms:
      hypersensitivity, toxicity, infection, and irritation. Some adverse health
      outcomes have been attributed to mold for which mechanisms of injury are not well
      defined or are implausible. This article discusses these adverse health outcomes,
      focusing predominantly on those for which valid associations have been
      established.

PMID- 17448363
TI  - Global pediatric environmental health.
AB  - Children are uniquely vulnerable to environmental health problems. Developed
      countries report as the most common problems ambient (outdoor) air pollution and
      lead. Developing countries have a wider range of common problems, including
      childhood injuries, indoor air pollution, infectious disease, and poor sanitation
      with unsafe water. Globally, the agencies of the United Nations act to protect
      children and perform essential reporting and standards-setting functions.
      Conditions vary greatly among countries and are not always better in developing
      countries. Protecting the health of children requires strengthening the public
      health and medical systems in every country, rather than a single global agenda.

PMID- 17448364
TI  - Safe and healthy school environments.
AB  - Children spend much of their waking time at school. Many of the factors in the
      school environment can be improved with careful planning and allocation of
      resources. The pediatrician, as a child advocate, is in an excellent position to
      influence the allocation of school resources to improve the educational outcome.
      This article summarizes some of the current understanding gathered from applying
      an environmental health approach to the school setting and provides a basis for
      the interested physician and other child advocate to learn more and get involved.

PMID- 17448365
TI  - Environmental health disparities: environmental and social impact of industrial
      pollution in a community - the model of Anniston, AL.
AB  - The health and well-being of children are critically dependent on the environment
      in which they live. This article explores the complex relationship between the
      environment in which a child lives and the environmental factors that can
      adversely affect health and development. It also examines how awareness of these
      adverse factors can be helpful in promoting optimal health for children through
      the societal infrastructures that deal with health, the environment, and social
      justice.

PMID- 17448366
TI  - Medical laboratory investigation of children's environmental health.
AB  - Medical laboratory testing is vital for investigating and managing children who
      have environmentally related disorders and children with environmental chemical
      exposures. Few of these compounds can be measured in a routine clinical service
      laboratory. An understanding of the exposure circumstances and toxicology of the
      agent is required for the ordering and interpretation of tests. Test
      interpretation requires understanding of the capabilities and limitations of
      these tests. Adequate investigation, management, and follow-up of exposed
      children are mandatory.

PMID- 17448367
TI  - Attacking obesity: lessons from smoking.
AB  - For the first time since the Civil War, American life expectancy is projected to
      decrease, owing to the diseases associated with obesity such as diabetes,
      ultimately causing cardiovascular death. In the past 30 years, the prevalence of
      obesity among U.S. adults has doubled, as has the incidence of type 2 diabetes.
      Enough data. The Surgeon General should attack obesity the same way as smoking in
      1964, with: 1) Advisory Council creation of public statements; 2) warning labels
      and menu information in all restaurants; 3) legislation for tax incentives for
      industry to promote worksite health; and 4) consideration of taxation of fatty
      food; the cigarette tax is now 42%. It is abundantly clear that in short order,
      obesity will kill more people than smoking. The time has come for the country to
      get serious about obesity and take lessons from our nation's campaign to reduce
      smoking. As patient advocates, scientists, and medical professionals,
      cardiologists should appropriately take the lead.

PMID- 17448368
TI  - Polymer-based, paclitaxel-eluting TAXUS Liberte stent in de novo lesions: the
      pivotal TAXUS ATLAS trial.
AB  - OBJECTIVES: The goal of this research was to assess non-inferiority of the next
      generation TAXUS Liberte stent (Boston Scientific Corp., Natick, Massachusetts)
      versus the TAXUS Express stent (Boston Scientific Corp.). BACKGROUND: The
      introduction of drug-eluting stents (DES) has shifted clinical practice towards
      more complex lesion subsets, prompting the need for more deliverable DES. TAXUS
      Liberte was designed to combine the established polymer-based, paclitaxel-elution
      TAXUS technology with the more advanced Liberte stent platform. METHODS: The
      TAXUS ATLAS study is a global, prospective, single-arm trial evaluating outcomes
      in de novo coronary lesions visually estimated to be 10 to 28 mm in length in
      vessels 2.5 to 4.0 mm in diameter. The control group is an entry-criteria-matched
      population of TAXUS Express patients from the TAXUS IV and V trials. The primary
      end point is non-inferiority of TAXUS Liberte versus TAXUS Express for 9-month
      target vessel revascularization. RESULTS: Despite similar inclusion criteria,
      quantitative coronary angiography-determined baseline lesion characteristics were
      significantly more complex for TAXUS Liberte than TAXUS Express. The primary non
      inferiority end point was met with the 1-sided 95% confidence bound of 2.98% less
      than the pre-specified non-inferiority margin of 3% (p = 0.0487). CONCLUSIONS:
      Despite the treatment of more complex lesions with TAXUS Liberte, the primary end
      point was met, demonstrating that TAXUS Liberte is non-inferior to TAXUS Express.
      The successful transfer of the proven TAXUS technology to the more advanced TAXUS
      Liberte platform was demonstrated. (TAXUS ATLAS: TAXUS Liberte-SR Stent for the
      Treatment of De Novo Coronary Artery Lesions;
      http://www.clinicaltrials.gov/ct/show/NCT00371709?order=1; NCT00371709).

PMID- 17448369
TI  - Fc(gamma) receptors IIa on cardiomyocytes and their potential functional
      relevance in dilated cardiomyopathy.
AB  - OBJECTIVES: The purpose of this study was to investigate how cardiac
      autoantibodies might contribute to cardiac dysfunction in patients suffering from
      dilated cardiomyopathy (DCM). BACKGROUND: In the majority of DCM patients, it is
      possible to detect antibodies with negative inotropic effect on cardiomyocytes.
      The manner in which these antibodies impair cardiac function is poorly
      understood. METHODS: Immunoglobulin (Ig)G was prepared from plasma of 11 DCM
      patients containing antibodies that induced a negative inotropic effect on
      cardiomyocytes. We analyzed the effects of antibodies/IgG fragments on calcium
      transients and on systolic cell shortening of adult rat cardiomyocytes and
      investigated the dependency of these effects on potential cardiomyocyte Fc
      receptors. RESULTS: In contrast to control subjects, intact IgG from DCM patients
      reduced calcium transients and cell shortening of cardiomyocytes. The F(ab')2
      fragments of these antibodies did not induce these effects but inhibited the
      functional effects of DCM-IgG of the respective patients' IgG. These effects were
      also inhibited by Fc fragments of normal IgG. Reconstitution of the Fc part by
      incubation of cardiomyocytes with DCM-F(ab')2 fragments followed by goat-anti
      human-F(ab')-IgG again induced reduction of cell shortening and of calcium
      transients. In rat and human ventricular cardiomyocytes, Fc(gamma) receptors IIa
      (CD32) were demonstrated by immunofluorescence. CONCLUSIONS: Our findings
      indicate that DCM-IgG-F(ab')2 bind to their cardiac antigen(s), but the Fc part
      might trigger the negative inotropic effects via the newly detected Fc(gamma)
      receptor on cardiomyocytes. These results point to a novel potential mechanism
      for antibody-induced impairment of cardiac function in DCM patients.

PMID- 17448370
TI  - Heartache of fc receptors.

PMID- 17448371
TI  - A randomized, placebo-controlled trial assessing the effects of rosiglitazone on
      echocardiographic function and cardiac status in type 2 diabetic patients with
      New York Heart Association Functional Class I or II Heart Failure.
AB  - OBJECTIVES: This study investigated the effects of rosiglitazone (RSG) on left
      ventricular ejection fraction (LVEF) in subjects with type 2 diabetes (T2DM) and
      pre-existing chronic heart failure (CHF) (New York Heart Association [NYHA]
      functional class I to II). BACKGROUND: Fluid retention is an important
      consideration in the use of thiazolidinediones in T2DM patients because it could
      exacerbate symptoms or precipitate decompensation in those with previously stable
      CHF. METHODS: A total of 224 patients with T2DM and NYHA functional class I to II
      CHF with LVEF < or =45% were randomized to a 52-week treatment with RSG (4 to 8
      mg daily, n = 110) or placebo (PLB) (n = 114) in addition to background
      antidiabetes therapy. Treatment was uptitrated to achieve target fasting plasma
      glucose <126 mg/dl; CHF medications were adjusted as appropriate. RESULTS: The
      LVEF was similar in both groups at baseline (RSG 35.3 +/- 6.2%, PLB 35.7 +/-
      7.8%) and after 52 weeks of treatment (mean difference 1.49%, p = 0.1). Glycemic
      control was significantly better in the RSG group (mean difference in hemoglobin
      A1c -0.65%, p < 0.0001). There were significantly more adjudicated events in the
      RSG group of new or worsening edema (RSG n = 28 [25.5%]; PLB n = 10 [8.8%]; p =
      0.005) and increased CHF medication (RSG n = 36 [32.7%], PLB n = 20 [17.5%]; p =
      0.037), but no significant difference between groups for other adjudicated end
      points. A similar proportion of patients withdrew from each treatment group
      because of adverse events. CONCLUSIONS: After 52 weeks of treatment, RSG improved
      glycemic control but did not adversely affect LVEF in patients with T2DM and NYHA
      functional class I to II CHF. More fluid-related events occurred with RSG,
      although these generally did not lead to withdrawal from the study.

PMID- 17448372
TI  - Fluid retention with thiazolidinediones: does the mechanism influence the
      outcome?

PMID- 17448373
TI  - Phase analysis of gated myocardial perfusion single-photon emission computed
      tomography compared with tissue Doppler imaging for the assessment of left
      ventricular dyssynchrony.
AB  - OBJECTIVES: The purpose of this study was to compare left ventricular (LV)
      dyssynchrony assessment by gated myocardial perfusion single-photon emission
      computed tomography (SPECT) (GMPS) and tissue Doppler imaging (TDI). BACKGROUND:
      Recently, it has been suggested that LV dyssynchrony is an important predictor of
      response to cardiac resynchronization therapy (CRT); dyssynchrony is
      predominantly assessed by TDI with echocardiography. Information on LV
      dyssynchrony can also be provided by GMPS with phase analysis of regional LV
      maximal count changes throughout the cardiac cycle, which tracks the onset of LV
      thickening. METHODS: In 75 patients with heart failure, depressed LV function,
      and wide QRS complex, GMPS and 2-dimensional echocardiography, including TDI,
      were performed as part of clinical screening for eligibility for CRT. Clinical
      status was evaluated with New York Heart Association functional classification, 6
      min walk distance, and quality-of-life score. Different parameters (histogram
      bandwidth, phase SD, histogram skewness, and histogram kurtosis) of LV
      dyssynchrony were assessed from GMPS and compared with LV dyssynchrony on TDI
      with Pearson's correlation analyses. RESULTS: Histogram bandwidth and phase SD
      correlated well with LV dyssynchrony assessed with TDI (r = 0.89, p < 0.0001 and
      r = 0.80, p < 0.0001, respectively). Histogram skewness and kurtosis correlated
      less well with LV dyssynchrony on TDI (r = -0.52, p < 0.0001 and r = -0.45, p <
      0.0001, respectively). CONCLUSIONS: The LV dyssynchrony assessed from GMPS
      correlated well with dyssynchrony assessed by TDI; histogram bandwidth and phase
      SD showed the best correlation with LV dyssynchrony on TDI. These parameters seem
      most optimal for assessment of LV dyssynchrony with gated SPECT. Outcome studies
      after CRT are needed to further validate the use of GMPS for assessment of LV
      dyssynchrony.

PMID- 17448374
TI  - Early prediction of infarct size by strain Doppler echocardiography after
      coronary reperfusion.
AB  - OBJECTIVES: The objective of this study was to investigate whether strain Doppler
      echocardiography performed immediately after revascularization by percutaneous
      coronary intervention could predict the extent of myocardial scar, determined by
      contrast-enhanced magnetic resonance imaging (MRI). BACKGROUND: There is
      considerable variability in survival rate after percutaneous coronary
      intervention, and accurate early risk stratification is therefore of major
      clinical importance. METHODS: Thirty individuals with acute anterior myocardial
      infarction were examined with longitudinal strain by Doppler 1.5 h after
      revascularization. The extent of scarring 9 months later was analyzed by MRI in
      16 corresponding myocardial segments. Strain in all left ventricular segments was
      averaged to obtain a global value. Infarct size was estimated by clinical
      parameters and cardiac markers. RESULTS: A good correlation was found between the
      global strain and total infarct size (R = 0.77, p < 0.00001). A multivariate
      regression analysis showed that global peak strain and serum glutamic oxaloacetic
      transaminase correlated with the infarct size measured by MRI (p = 0.0001 and p =
      0.001, respectively). Furthermore, a clear inverse relationship was found between
      the segmental strain and the transmural extent of infarction in each segment (R =
      0.67, p < 0.0001). CONCLUSIONS: This study demonstrates that assessment of
      regional and global strain at 1.5 h after reperfusion therapy correlates with
      size and transmural extent of myocardial infarction as determined by contrast
      enhanced MRI. The novel global strain parameter is a valuable predictor of the
      total extent of myocardial infarction and may therefore be an important clinical
      tool for risk stratification in the acute phase of myocardial infarction.

PMID- 17448375
TI  - Scavenging free radicals by low-dose carvedilol prevents redox-dependent Ca2+
      leak via stabilization of ryanodine receptor in heart failure.
AB  - OBJECTIVES: We investigated whether defective intracellular Ca2+ handling is
      corrected by carvedilol in heart failure. BACKGROUND: In heart failure, the
      interaction between the N-terminal and central domains of the ryanodine receptor
      (RyR), the domains where many mutations have been found in patients with
      catecholaminergic polymorphic ventricular tachycardia (CPVT), is defective, as
      shown in our recent report. METHODS: Sarcoplasmic reticulum vesicles were
      isolated from canine left ventricular muscle (normal or 4-weeks rapid ventricular
      pacing). The RyR was labeled with the fluorescent conformational probe
      methylcoumarin acetate (MCA) with DPc10 (a synthetic peptide corresponding to
      Gly2460-Pro2495 of RyR, one of the mutable domains in CPVT) as a site-direction
      carrier. RESULTS: Normal cardiac function was well preserved in carvedilol
      treated/paced dogs (CV+) but not in the untreated/paced dogs (CV-). In CV-, the
      interdomain interaction within RyR was defective (i.e., in an unzipped state), as
      determined by the fluorescence quenching technique. However, in CV+, the domain
      interaction remained normal (i.e., in a zipped state). In CV-, oxidative stress
      of RyR (reduction in the number of free thiols) was severe, but it was negligible
      in CV+. In (CV-) failing cardiomyocytes, incubation with low-dose CV (30 nmol/l),
      which eliminated intracellular reactive oxygen species with no acute effect on
      cell shortening, markedly improved the contractile function and Ca2+ transient.
      However, after domain unzipping by DPc10, CV was without effect. CONCLUSIONS:
      Carvedilol, at a concentration that is sufficient to produce antioxidant effect,
      improves the intracellular Ca2+ handling and contractile dysfunction by
      correcting defective interdomain interaction within the RyR in the failing heart.

PMID- 17448376
TI  - Plasma brain natriuretic peptide-guided therapy to improve outcome in heart
      failure: the STARS-BNP Multicenter Study.
AB  - OBJECTIVES: The aim of this multicenter study was to evaluate the prognostic
      impact of a therapeutic strategy using plasma brain natriuretic peptide (BNP)
      levels. BACKGROUND: The prognosis of chronic heart failure (CHF) remains poor,
      even among patients treated in specialized departments. METHODS: A total of 220
      New York Heart Association functional class II to III patients considered
      optimally treated with angiotensin-converting enzyme inhibitors (ACEIs), beta
      blockers, and diuretics by CHF specialists were randomized to medical treatment
      according to either current guidelines (clinical group) or a goal of decreasing
      BNP plasma levels <100 pg/ml (BNP group). Outpatient visits were scheduled every
      month for 3 months, then every 3 months. The primary combined end point was CHF
      related death or hospital stay for CHF. RESULTS: Both groups were similar for
      baseline clinical and biological characteristics. Left ventricular ejection
      fraction was slightly lower in the BNP group than in the clinical group (29.9 +/-
      7.7% vs. 31.8 +/- 8.4%, p = 0.05). At the end of the first 3 months, all types of
      drugs were changed more frequently in the BNP group. Mean dosages of ACEIs and
      beta-blockers were significantly higher in the BNP group (p < 0.05), whereas the
      mean increase in furosemide dosage was similar in both groups. During follow-up
      (median 15 months), significantly fewer patients reached the combined end point
      in the BNP group (24% vs. 52%, p < 0.001). CONCLUSIONS: In optimally treated CHF
      patients, a BNP-guided strategy reduced the risk of CHF-related death or hospital
      stay for CHF. The result was mainly obtained through an increase in ACEI and beta
      blocker dosages.

PMID- 17448377
TI  - The year in atherothrombosis.

PMID- 17448379
TI  - Effect of polyunsaturated fatty acids on baroreflex function in heart failure
      patients.

PMID- 17448381
TI  - Use of electrocardiographic gating in computed tomography angiography of the
      ascending thoracic aorta.

PMID- 17448382
TI  - Computerized navigation surgery for the safe placement of palatal implants.
AB  - Palatal endosseous implants are increasingly recognized as an important
      alternative for achieving maximal intraoral orthodontic anchorage; however, their
      safe surgical placement is a matter of concern. Available palatal bone is
      frequently limited, and erroneous drilling can damage adjacent structures.
      Computerized navigation surgery is an advanced surgical modality in which the
      surgical drill is accurately tracked and animated in real time on the
      radiological image of the surgical site. In implant dentistry, this surgical
      modality allows accurate navigation of the implant drilling procedure and
      increases safety and accuracy, compared with conventional dental implant surgery.
      This article outlines the principles of computerized navigation surgery and
      describes its application for the placement of palatal orthodontic implants. The
      merits of this approach are particularly important for patients with limited
      palatal bone when implant placement requires high surgical precision.

PMID- 17448383
TI  - Correction of Class II deep overbite and dental and skeletal asymmetry with 2
      types of palatal miniscrews.
AB  - This case report describes the orthodontic treatment of a 31-year-old woman who
      had a Class II molar relationship, anterior crowding, deep overbite, maxillary
      dental midline deviation, vertical maxillary asymmetry, and a hyperdivergent
      facial pattern. The maxillary right first premolar and the left second premolar
      were extracted asymmetrically to correct the anterior crowding and the maxillary
      dental midline deviation. The maxillary molars were intruded with a midpalatal
      miniscrew, which helped to correct the vertical molar asymmetry and close the
      mandibular plane. The palatal miniscrew in the maxillary tuberosity was also used
      to provide anchorage reinforcement for retraction of the anterior teeth. After
      orthodontic treatment, dental and facial esthetics were greatly improved by
      treatment of anterior crowding and deep overbite, correction of the dental and
      skeletal asymmetry, and closure of the mandibular plane. At the 3-year follow-up,
      most of the treatment results had been maintained.

PMID- 17448385
TI  - Risks and complications of orthodontic miniscrews.
AB  - The risks associated with miniscrew placement should be clearly understood by
      both the clinician and the patient. Complications can arise during miniscrew
      placement and after orthodontic loading that affect stability and patient safety.
      A thorough understanding of proper placement technique, bone density and
      landscape, peri-implant soft-tissue, regional anatomic structures, and patient
      home care are imperative for optimal patient safety and miniscrew success. The
      purpose of this article was to review the potential risks and complications of
      orthodontic miniscrews in regard to insertion, orthodontic loading, peri-implant
      soft-tissue health, and removal.

PMID- 17448386
TI  - Systematic review of the experimental use of temporary skeletal anchorage devices
      in orthodontics.
AB  - INTRODUCTION: Our aim was to review the experimental literature to determine what
      is known about functional and morphological tissue reactions around
      orthodontically loaded temporary skeletal anchorage devices. METHODS: The PubMed
      electronic database and the reference citations in published articles were
      searched to the end of April 2006. The inclusion criteria were animal studies
      about orthodontically loaded skeletal anchorage consisting of metallic bone
      plates or screw implants of 2.2 mm diameter or less. Data on healing time, force
      application, stability, side effects, and osseointegration were collected by 2
      independent readers. RESULTS: Eight articles met the selection criteria. The
      healing times ranged from 0 to 12 weeks, and the amount of force varied from 25
      to 500 g. Implant stability was generally achieved without severe side effects.
      Direct bone-screw contact was reported to be 10% to 58%, and osseointegration
      increased with loading time. Nevertheless, no significant difference in bone
      screw contact was found between loaded and unloaded screw implants, or between
      tension and pressure sides of loaded implants. CONCLUSIONS: This review
      highlights some positive experimental findings that apply in clinical practice.
      However, questions concerning optimal force systems, surgical techniques and
      placement, and healing times remain. Future research should be well controlled
      and based on standardized protocols to test specific hypotheses.

PMID- 17448387
TI  - Determining the cessation of vertical growth of the craniofacial structures to
      facilitate placement of single-tooth implants.
AB  - INTRODUCTION: Single-tooth implants are commonly used to replace congenitally
      missing teeth in adolescent orthodontic patients. However, if implants are placed
      before cessation of facial growth, they will submerge relative to the adjacent
      erupting teeth. Therefore, it is important to know when facial growth is complete
      in postpubertal orthodontic patients. The purposes of this study were to
      determine and quantify the amount of vertical growth of the facial skeleton and
      the amount of eruption of the central incisors and the maxillary first molars
      after puberty. METHODS: Two or 3 lateral cephalograms taken at pretreatment,
      posttreatment, and 10 years postretention of 142 males and 159 females were
      evaluated. Linear regression models were used to determine changes in the
      parameters with increasing age. RESULTS: The findings indicate that (1) the
      growth of the facial skeleton continues after puberty; (2) there is a difference
      in the amount of growth between the sexes during the second decade of life, and
      after age 20 the intergender difference is substantially diminished; and (3) the
      rate of eruption of the maxillary central incisors in females seems to be greater
      than in males. Prediction tables are provided to help the clinician determine
      when to take cephalometric radiographs to assess the cessation of facial growth.
      CONCLUSIONS: The growth of the facial skeleton continues after puberty, but the
      amount of growth decreases steadily and after the second decade of life seems to
      be clinically insignificant.

PMID- 17448389
TI  - Root proximity is a major factor for screw failure in orthodontic anchorage.
AB  - INTRODUCTION: The purpose of this study was to evaluate root proximity as a risk
      factor for the failure of miniscrews used as orthodontic anchorage. METHODS: We
      used dental radiographs and 3-dimensional computed tomography images to examine
      216 titanium screws in 110 patients. Each screw was classified according to its
      proximity to the adjacent root. Category I, the screw was absolutely separate
      from the root; category II, the apex of the screw appeared to touch the lamina
      dura; and category III, the body of the screw was overlaid on the lamina dura. If
      the orthodontic force could be applied to the screw for 1 year (or until
      completion of orthodontic treatment), we recorded the screw anchorage as a
      success. RESULTS: The screws had a high success rate--above 80%. Screws placed in
      the maxilla had a significantly higher success rate than those in the mandible.
      There was a significant correlation between success rate and root proximity.
      There were significant differences in the success rates between categories I and
      II, I and III, and II and III. Although screws in all 3 categories in the maxilla
      and categories I and II in the mandible showed high success rates above 75%,
      screws in category III in the mandible had a low success rate of 35%.
      CONCLUSIONS: The proximity of a miniscrew to the root is a major risk factor for
      the failure of screw anchorage. This tendency is more obvious in the mandible.

PMID- 17448390
TI  - Bone thickness of the palate for orthodontic mini-implant anchorage in adults.
AB  - INTRODUCTION: The palate is a suitable site for the placement of orthodontic mini
      implants. This study was conducted to assess the bone thickness of the palate to
      provide a more reliable guide for mini-implant placement. METHODS: Computed
      tomographic records of 18 adults (9 men, 9 women) 18 to 35 years old (mean age,
      26.8 +/- 4.0 years) were used to measure the bone thickness of the midpalatal
      area and its vicinity posterior to the incisive foramen. Bone thickness was
      measured at 80 coordinates at regular mediolateral and anteroposterior intervals
      along the midpalatal suture. After the mean, minimum, and maximum values were
      obtained for the entire group and for the male and female groups, mediolateral
      and anteroposterior comparison was done, and the differences between sexes were
      evaluated. RESULTS: Individual variations were so great that high-resolution
      computed tomographic images are recommended for safety. Significant differences
      were seen between the male and female groups. The midpalatal area within 1 mm of
      the midsagittal suture had the thickest bone available in the whole palate. The
      thickness tended to decrease laterally and posteriorly. Maps of mean palatal bone
      thickness were made for visual comparison of placement locations and for
      selection of the mini-implant length. CONCLUSIONS: When a mini-implant could
      deviate from the midpalatal area by more than 1 mm, we recommend placing it not
      far posteriorly or using a shorter mini-implant.

PMID- 17448391
TI  - Surgical positioning of orthodontic mini-implants with guides fabricated on
      models replicated with cone-beam computed tomography.
AB  - INTRODUCTION: This article illustrates a new surgical guide system that uses cone
      beam computed tomography (CBCT) images to replicate dental models; surgical
      guides for the proper positioning of orthodontic mini-implants were fabricated on
      the replicas, and the guides were used for precise placement. The indications,
      efficacy, and possible complications of this method are discussed. METHODS:
      Patients who were planning to have orthodontic mini-implant treatment were
      recruited for this study. A CBCT system (PSR 9000N, Asahi Roentgen, Kyoto, Japan)
      was used to acquire virtual slices of the posterior maxilla that were 0.1 to 0.15
      mm thick. Color 3-dimensional rapid prototyping was used to differentiate teeth,
      alveolus, and maxillary sinus wall. A surgical guide for the mini-implant was
      fabricated on the replica model. Proper positioning for mini-implants on the
      posterior maxilla was determined by viewing the CBCT images. RESULTS: The
      surgical guide was placed on the clinical site, and it allowed precise pilot
      drilling and accurate placement of the mini-implant. CONCLUSIONS: CBCT imaging
      allows remarkably lower radiation doses and thinner acquisition slices compared
      with medical computed tomography. Virtually reproduced replica models enable
      precise planning for mini-implant positions in anatomically complex sites.

PMID- 17448392
TI  - Convenient removal of orthodontic mini-implants.
AB  - Temporary anchorage devices, such as orthodontic mini-implants, are now popular.
      We introduce a new method for removing orthodontic mini-implants that has proven
      to be safe, convenient, and time-saving.

PMID- 17448393
TI  - Three-dimensional evaluation of surgically assisted implant bone-borne rapid
      maxillary expansion: a pilot study.
AB  - INTRODUCTION: The purpose of this study was to evaluate 3-dimensional changes in
      dental, alveolar, and skeletal structures caused by a bone-borne implant
      supported rapid maxillary expansion device (Dresden distractor). METHODS: Axial
      computed tomography scans of 10 patients (mean age, 25.3 years) treated with the
      Dresden distractor were examined. Scans were taken immediately before and 9
      months after expansion. Distances in all 3 dimensions were calculated for 38
      skeletal, alveolar, and dental landmarks with respect to the reference point ELSA
      (point equidistant to both foramina spinosa). RESULTS: In the transverse
      dimension, a V-shaped opening of the suture was shown; the greatest amount of
      opening was anteriorly directed, with convergence of the suture opening in the
      posterior aspect of the palate. The expansion of the maxillary dental arch showed
      a V pattern similar to the opening of the suture. In the frontal view, expansion
      caused a wedge-shaped opening with its base at the central incisors and the
      estimated center of rotation next to the frontonasal suture. The alveolar
      processes tipped buccally (9.9 degrees to 13.3 degrees) as did the molars (2.5
      degrees to 3.5 degrees) and the premolars (3.0 degrees to 3.9 degrees). Less
      tipping of teeth compared with skeletal tipping (about 6 degrees to 9 degrees
      less) is related to the torque effect of the fixed appliance. CONCLUSIONS: The
      Dresden distractor is a minimally invasive bone-borne expansion appliance that
      protects teeth by inducing more skeletal than dental changes. This might be a
      precondition for stable postsurgical occlusion.

PMID- 17448394
TI  - Gambling with adolescent health.

PMID- 17448395
TI  - Gambling and health risk behaviors among U.S. college student-athletes: findings
      from a national study.
AB  - PURPOSE: To examine prevalence and associations of gambling problems and health
      risk behaviors among college athletes from the first national survey of gambling
      among U.S. college student-athletes. METHODS: Conducted by the National
      Collegiate Athletic Association (NCAA), this self-administered and anonymous
      survey collected information from a nationally representative sample of 20,739
      student-athletes. RESULTS: Males consistently had higher past-year prevalence of
      gambling than females (e.g., 62.4% of males reported some type of gambling vs.
      42.8% of females). Based on DSM-IV Gambling Screen, this study identified 4.3% of
      males and 0.4% of females as problem/pathological gamblers. A general upward
      trend existed that as the level of gambling problems increased, so did the
      prevalence of substance use, gorging/vomiting, and unprotected sex. Cross-group
      comparisons by gambler type were all significant. Problem and pathological
      gamblers also experienced significantly more drug/alcohol-related problems than
      non-gamblers and social gamblers. CONCLUSIONS: Direct associations found between
      gambling and multiple risk behaviors in college student-athletes support the
      persistence of the youth problem-behavior syndrome and suggest the need for multi
      faceted initiatives to tackle these risk behaviors simultaneously.

PMID- 17448396
TI  - Meningococcal conjugate vaccine uptake, measured by Michigan's immunization
      registry.
AB  - PURPOSE: To describe the uptake of meningococcal conjugate vaccine (MCV4) in
      Michigan adolescents following its approval in January 2005, and compare it to
      the use of meningococcal polysaccharide vaccine (MPSV4) in 2004. METHODS: All
      available records of meningococcal immunizations given between February 1986 and
      March 2006 were obtained from the Michigan Childhood Immunization Registry
      (MCIR), which is used by about 95% of Michigan immunization providers. During
      late 2005 and early 2006, these records were analyzed by immunization type,
      administration date, recipient age, and health care provider type (public or
      private). RESULTS: The MCIR contained 63,253 meningococcal immunizations. A total
      of 15.2% were given in 2004, 68.8% in 2005, and 10.8% in 2006. In those years,
      most immunizations occurred in June, July, and August. In 2005, 85.2% were MCV4.
      In 2004, 17 to 18-year olds received nearly all meningococcal immunizations; in
      2005, 11 to 16-year olds received 58.0% of them. Estimates of immunization
      coverage were 4.0% for 11 to 12-year olds, 3.4% for 13 to 16-year olds, 5.9% for
      17 to 19-year olds, and 19% for freshmen entering college. CONCLUSIONS: Compared
      to 2004, in 2005 there was a large increase in the number of doses administered,
      with more MCV4 than MPSV4. Patterns of immunization were consistent with the
      Advisory Committee on Immunization Practices (ACIP) recommendations. Coverage of
      Michigan adolescents is low, but increased in 2005 compared with 2004.

PMID- 17448397
TI  - The impact of state policies on vaccine coverage by age 13 in an insured
      population.
AB  - PURPOSE: To determine the impact of state policies on vaccine coverage among
      adolescents with managed care insurance. METHODS: We used the 2003 Health Plan
      Employer Data and Information Set to determine state-specific hepatitis B and
      varicella vaccine coverage among children with managed care insurance who turned
      13 years in 2002. Our outcomes of interest were receipt of hepatitis B and
      varicella vaccines by age 13. Utilizing weighted least-squares methods, multiple
      linear regression models were developed to evaluate the relationship between
      hepatitis B and varicella vaccine coverage and state policies, while controlling
      for state sociodemographic variables. RESULTS: Across 28 states, adolescent
      hepatitis B vaccine coverage ranged from 35.3% to 80.5% (mean = 55.3%) and
      varicella vaccine coverage ranged from 22.9% to 7.6% (mean = 42.3%). In separate
      multiple regression models, after adjusting for potentially confounding
      sociodemographic variables, middle school mandates were significantly associated
      with hepatitis B vaccine coverage (p = .002) and varicella vaccine coverage (p =
      .024). Other policies, including universal purchase of vaccines and availability
      of philosophic exemptions, were not associated with vaccine coverage in this
      insured population. CONCLUSIONS: In this population of insured adolescents,
      middle school vaccine mandates were the only state policy associated with
      improved hepatitis B and varicella vaccine coverage. Mandates are an effective
      method for promoting adolescent immunization.

PMID- 17448398
TI  - Mycoplasma genitalium among adolescent women and their partners.
AB  - PURPOSE: Mycoplasma genitalium is a possible sexually transmitted pathogen and
      its study among the adolescent age group has been limited. In this longitudinal
      study, the epidemiology, natural history, and associated clinical findings of M.
      genitalium among adolescents in a primary care setting were explored. METHODS: A
      sample of 383 young women (14-17 years of age) and 117 male partners provided
      sexual behavior data and urogenital samples for polymerase chain reaction testing
      to detect M. genitalium, Chlamydia trachomatis, and other sexually transmitted
      infections. Women were tested quarterly for up to 27 months and, during every
      other quarter, tested weekly. The presence of any signs or symptoms of infection
      among the female subjects was also documented. RESULTS: Cumulatively, 13.6%
      (52/383) of women tested positive for M. genitalium. All women with M.
      genitalium, except one, were sexually experienced. M. genitalium was associated
      with number of sexual partners (p < .001) and C. trachomatis infection (p < .03).
      M. genitalium was more likely among male partners of M. genitalium-positive women
      (p < .02); 31.3% of untreated M. genitalium cases had infection lasting over 8
      weeks. M. genitalium was not associated with the presence of clinical signs or
      symptoms of infection. CONCLUSIONS: Findings support sexual transmissibility of
      M. genitalium and add to understanding of M. genitalium natural history and
      clinical findings.

PMID- 17448399
TI  - Urinary symptoms in adolescent females: STI or UTI?
AB  - PURPOSE: To determine if urinary symptoms or urinary tract infections (UTI) were
      associated with sexually transmitted infections (STI) and which history,
      clinical, and laboratory findings could distinguish these infections in
      symptomatic women. METHODS: A cross-sectional sample of 296 sexually active
      females aged 14-22 years attending a hospital-based teen health center or
      emergency department were recruited. Genitourinary symptoms, medical and sexual
      history, and urinalysis results were recorded. STI was defined as a vaginal swab
      positive for Trichomonas vaginalis or urine nucleic acid amplification test
      positive for Neisseria gonorrheae or Chlamydia trachomatis. A urine culture with
      >10,000 colonies of a single pathogen was considered a positive UTI. RESULTS: In
      the full sample, prevalence of UTI and STI were 17% and 33%, respectively.
      Neither urinary symptoms nor UTI was significantly associated with STI. Further
      analyses are reported for the 154 (51%) with urinary symptoms: Positive urine
      leukocytes, more than one partner in the last three months and history of STI
      predicted STI. Urinalysis results identified four groups: (1) Normal urinalysis
      67% had no infection; (2) Positive nitrites or protein-55% had UTI; (3) Positive
      leukocytes or blood-62% had STI; and (4) Both nitrites/protein and
      leukocytes/blood positive-28% had STI and 65% had UTI. Those without a documented
      UTI were more likely to have trichomoniasis than those with a UTI, and 65% of
      those with sterile pyuria had STI, mainly trichomoniasis or gonorrhea.
      CONCLUSIONS: Adolescent females with urinary symptoms should be tested for both
      UTI and STIs. Urinalysis results may be helpful to direct initial therapy.

PMID- 17448400
TI  - Anxiety and depressive disorders are associated with smoking in adolescents with
      asthma.
AB  - PURPOSE: To evaluate the association between mental health indicators (including
      meeting criteria for one or more DSM-IV [Diagnostic and Statistical Manual of
      Mental Disorders-fourth edition] anxiety or depressive disorders) and
      susceptibility to smoking or current smoking among youth with asthma and to
      evaluate the impact of smoking on asthma symptoms and self-management. METHODS:
      We conducted telephone interviews with a population-based sample of 11- to 17
      year-old youth and their parents (n = 769). Interview content included questions
      on smoking behaviors, asthma symptoms and treatment, externalizing behavior, and
      a structured psychiatric interview to assess DSM-IV anxiety and depressive
      disorders. RESULTS: Five percent of youth were smokers and 10.6% indicated that
      they were "susceptible to smoking." Smoking was more common among youth with
      mental health disorders. Anxiety/depressive disorders were present in 14.5% of
      nonsmokers, 19.8% of susceptible nonsmokers, and 37.8% of smokers. After
      controlling for important covariates, youth with more than one anxiety and
      depressive disorder were at over twofold increased risk for being a smoker.
      Similarly, for each one-point increase in externalizing disorder symptoms, youth
      had a 10% increase in likelihood of being a smoker and a 4% increase in risk for
      "susceptibility to smoking." Youth who were smokers reported more asthma
      symptoms, reduced functioning due to asthma, less use of controller medicines,
      and more use of rescue medications. CONCLUSIONS: Comorbid mental health disorders
      are associated with increased risk of smoking in youth with asthma. Smoking is
      associated with increased asthma symptom burden and decreased controller
      medication use. Interventions for youth with asthma should consider screening for
      and targeting these behavioral concerns.

PMID- 17448401
TI  - Pediatric primary care providers and adolescent depression: a qualitative study
      of barriers to treatment and the effect of the black box warning.
AB  - PURPOSE: The recent black box warning on antidepressants has drawn attention to
      controversies regarding the treatment of adolescent depression in primary care
      settings, but little is known about how providers decide to treat depressed youth
      and what resources are employed. METHODS: We conducted focus groups with 35
      providers and staff in nine community-based pediatric practices in rural and
      urban settings of western Washington State. Discussion topics included perceived
      barriers to the treatment of depression in youth, how providers addressed these
      barriers, and the impact of the recent Federal Drug Administration (FDA) black
      box warning. Focus groups were audiotaped and professionally transcribed.
      Qualitative content analysis was conducted using Atlas ti software and
      differences in coding were resolved via discussion by three independent
      reviewers. RESULTS: Based on analysis of interviews, a conceptual model was
      developed detailing factors influencing primary care providers' (PCP) decisions
      about depression treatment. The three key themes that influenced doctors'
      decisions about treating depression were lack of availability of mental health
      resources in the community, feeling responsible for helping based on long
      standing relationships with patients and families, and patient and family beliefs
      and preferences regarding treatment. Most of the approaches to address barriers
      were not systemized and were physician dependent. Most providers expressed
      concern about recent antidepressant warnings, but many continued to treat and
      none had developed new strategies for closer monitoring of youth initiating
      treatment with antidepressants. CONCLUSION: The decision of when and how PCPs
      decide to treat adolescent depression is strongly influenced by PCP perceptions
      of their role in treatment, availability of other treatment resources, and family
      and patient preferences and resources. Few practices have developed changes in
      the approach to practice needed to meet FDA black-box recommendations regarding
      close monitoring of response to medications.

PMID- 17448402
TI  - Is religiosity a protective factor against substance use in young adulthood? Only
      if you're straight!
AB  - PURPOSE: Previous research has documented that substance use peaks during young
      adulthood and that religiosity provides a protective effect against binge
      drinking, marijuana use, and cigarette smoking. The majority of these studies do
      not examine sexual identity as it relates to these factors. Drawing on social
      influence and developmental theories, we tested the hypothesis that religiosity
      would provide a protective effect for heterosexual but not sexual minority young
      adults. METHOD: Waves 1 and 3 of the National Longitudinal Study of Adolescent
      Health provided data for the study. Three young adult sexual identity groups were
      formed: sexual minorities who did not report same-sex attraction at Wave 1 (NA),
      sexual minorities who did report same-sex attraction at Wave 1 (SSA), and
      heterosexuals (HET) (sample n = 764). RESULTS: Religiosity measured at baseline
      had no significant effect on past-year substance use, measured six years later in
      sexual minority young adults. For heterosexual young adults, each unit increase
      in religiosity reduced the odds of binge drinking by 9%, marijuana use by 20%,
      and cigarette smoking by 13%. CONCLUSIONS: Religiosity was not protective against
      substance use in sexual minority young adults, cautioning against over
      generalizing previous findings about the protective effects of religiosity.
      Future studies that 1) consider the social context for sexual identity
      development, 2) model both risk and protective factors, and 3) use
      multidimensional measures of religiosity (and spirituality) and sexual identity
      are needed to build the necessary knowledge base for effective health promotion
      efforts among sexual minority youth and young adults.

PMID- 17448403
TI  - Risk and protective factors for adolescent substance use: findings from a study
      in selected Central American countries.
AB  - PURPOSE: To identify the prevalence of substance use and problems with use, and
      risk and protective factors at different levels of the adolescent's ecology
      associated with substance use among adolescents in selected Central American
      countries. METHODS: Results of a survey of 17,215 students from Panama, Costa
      Rica, and Guatemala conducted in 2000-2001 served as the basis for the analyses.
      Lifetime use of alcohol, tobacco, marijuana, and five other drugs (inhalants,
      tranquilizers, cocaine, crack, and ecstasy), and problems with drugs and alcohol
      were the outcome variables. Risk factors included dysregulation, family problems
      with drugs/alcohol, negative family interactions, school disengagement, peer
      deviance, and exposure to community violence. Protective factors included a
      personal belief in God, positive family interactions, parent religiosity, and
      positive student-teacher interaction. Both hierarchical linear regression and
      logistic regression analyses were used to model main and interaction effects of
      risk and protective factors. RESULTS: There was a linear association between
      number of risk and protective factors and substance use, however, risk factors
      were more strongly associated with substance use than were protective factors.
      There were significant risk-by-protective-factor interactions for alcohol and
      marijuana use, and for problems with drugs and alcohol. Risk interacted most
      consistently with a personal belief in God, but also with parent religiosity and
      with student-teacher communication. CONCLUSIONS: It is important to consider risk
      and protective factors at different levels of an adolescent's ecology. Prevention
      and intervention efforts should focus on interactions adolescents have in
      different microsystems (e.g., with parents, teachers, and peers).

PMID- 17448404
TI  - The "Six T's": barriers to screening teens for substance abuse in primary care.
AB  - PURPOSE: To identify barriers to adolescent substance abuse screening in primary
      care. METHODS: Focus groups were held at six primary care sites with a total of
      38 providers. Providers brainstormed a list of barriers, collectively grouped
      similar barriers, and voted to produce a final ranked list. Two investigators
      qualitatively analyzed field notes and transcripts to triangulate findings,
      ranked the barriers across all sites by the number of groups identifying the
      barrier, then calculated a mean ranking (MR) for each. RESULTS: The most commonly
      identified barrier was insufficient time (MR 1.8). Lack of training in how to
      manage a positive screen was ranked second (MR 1.7), but was linked to the first.
      Providers reported they had enough time to administer a short screen, but
      insufficient time to manage a positive result during the well care visit. The
      need to triage competing problems (MR 3.0), lack of treatment resources (MR 3.3),
      tenacious parents who would not leave the room for a confidential discussion (MR
      2.5), and unfamiliarity with screening tools (MR 3.0) were also noted by more
      than one group. CONCLUSIONS: Insufficient time and lack of training in how to
      manage positive screens are the greatest barriers to screening adolescents for
      substance abuse. This suggests that some providers might differentially avoid
      screening youth who they suspect will screen positive, yet these patients would
      benefit most from early recognition. More research is needed on effective ways to
      manage positive substance abuse screens in primary care.

PMID- 17448405
TI  - Adolescent physical activity and perceived competence: does change in activity
      level impact self-perception?
AB  - PURPOSE: To determine whether change in physical activity level impacts
      adolescents' self-perceptions. METHODS: Using questionnaire responses from the
      Growing Up Today Study (GUTS) in 1997 and 1999, we evaluated data from 5260 girls
      and 3410 boys. Physical activity changes were compared to changes in perceived
      competence in three domains (social, athletic, and scholastic) as well as in
      global self-worth. Analyses controlled for sibling clustering as well as for
      potential confounders, including body mass index, cigarette smoking, baseline
      activity levels, and baseline self-perception scores. RESULTS: For girls and
      boys, increase in physical activity was positively associated with change in
      social and athletic (p < .0001), but not scholastic or global, self-perception.
      Compared to those with little or no change in activity, those who increased
      physical activity were more likely to have increased self-perception measures.
      Girls who increased physical activity by 5 or more hours/week were at least 33%
      more likely to have increased social self-perception, and at least 44% more
      likely to have increased athletic self-perception. In boys, those who increased
      activity by 10 or more hours/week were 45% more likely to have increased social
      self-perception. The reverse was also true; for both girls and boys, those with
      decreased physical activity were more likely to have decreased self-perception
      scores. CONCLUSIONS: This research indicates that increased physical activity has
      a positive impact on athletic and social self-perception in girls and boys.

PMID- 17448406
TI  - Social and romantic outcomes in emerging adulthood among survivors of childhood
      cancer.
AB  - PURPOSE: To examine social and romantic outcomes among survivors of childhood
      cancer and comparison peers during the transition from adolescence to emerging
      adulthood. METHODS: Families were recruited when the children with cancer were 8
      15-years-old and on initial treatment for a malignancy that did not primarily
      affect the central nervous system (i.e., non-CNS). At that time, each child with
      cancer was matched to a classmate of similar age, gender, and race for inclusion
      in a comparison group. For the current follow-up (7.29 years post-diagnosis), 56
      survivors, 60 comparison peers, and their parents completed questionnaires after
      the youth's 18th birthday. Severity of treatment and late effects were rated by
      health care providers. RESULTS: Survivors and comparison peers were similar on a
      variety of outcomes, including family background, social self-concept, social
      competence, family relationships, friendships, and romantic relationships.
      Mothers reported that survivors engaged in fewer activities than comparison
      peers. The proportion of participants who lived with their parents, were dating,
      and expressed plans to marry or have children was similar between groups. Initial
      treatment intensity, time since diagnosis, and severity of late effects were
      associated with some indices of social adjustment. CONCLUSIONS: The social and
      romantic outcomes of survivors of non-CNS cancer were similar to comparison peers
      during the transition from adolescence to emerging adulthood. Disease and
      treatment factors had limited associations with outcomes. Clinical interventions
      to assist social development may not be necessary for all survivors, but
      additional research is needed to identify subgroups at risk for difficulties.

PMID- 17448407
TI  - Mental health and gambling in urban female adolescents.
AB  - This study explores differences in mental health and behavioral disturbances
      between female gamblers versus nongamblers from a community sample of 232 female
      urban youth. Female adolescent recreational gambling was associated with high
      levels of childhood hyperactivity measured at age 6, past-year substance use, and
      past-year anxiety symptoms.

PMID- 17448408
TI  - Anticipated acceptance of HPV vaccination at the baseline of implementation: a
      survey of parental and adolescent knowledge and attitudes in Finland.
AB  - We evaluated acceptance of human papillomavirus (HPV) vaccination by adolescents
      and their parents, 83% and 86% of whom accepted vaccination. Improving knowledge
      and awareness of HPV, and addressing parental concerns about vaccinating
      adolescents, most notably on vaccinating against a sexually transmitted disease,
      should help tackle factors associated with being resistant to accepting HPV
      vaccination.

PMID- 17448409
TI  - Variables associated with weapon-carrying among young adolescents in southern
      California.
AB  - In a multiethnic sample of 542 young adolescents, we examined the relation
      between victimization and weapon carrying in a school-based prevalence survey.
      Physical victimization contributed to this association in boys and relational
      victimization contributed to this association among girls. The findings support a
      gender-specific approach to designing violence prevention programs in the
      schools.

PMID- 17448410
TI  - "Energy Up": a novel approach to the weight management of inner-city teens.
AB  - There are few successful adolescent obesity prevention programs. We evaluated
      "Energy Up," an innovative program for inner-city girls that focuses on addictive
      food avoidance, exercise, and self-esteem building. Over a 9-month period, obese
      participants lost 12.9 pounds and overweight participants lost 2.9 pounds,
      prompting expansion to other schools.

PMID- 17448411
TI  - Buprenorphine replacement therapy for adolescents with opioid dependence: early
      experience from a children's hospital-based outpatient treatment program.
AB  - Opioid use by adolescents is on the rise and replacement therapy is an effective
      treatment. Methadone replacement has been used safely and effectively with
      adults, but methadone programs are often unattractive to teenagers. Buprenorphine
      is a new replacement therapy that has been shown to be as effective as high dose
      methadone and may be better suited for the treatment of younger patients. We
      describe the experiences of several adolescent patients who received treatment
      from an outpatient adolescent substance abuse program that operates within a
      children's hospital, with an emphasis on issues of adolescent development.

PMID- 17448412
TI  - The effect of spironolactone use on heart failure mortality: a population-based
      study.
AB  - BACKGROUND: Spironolactone use for heart failure (HF) has increased dramatically
      after the publication of the Randomized Aldactone Evaluation Study trial; yet,
      few studies have examined its real-world impact. We aimed to determine the
      population effect of spironolactone use on mortality in HF patients discharged
      from hospital. METHODS AND RESULTS: All patients discharged alive between October
      1997 and December 2001 in Nova Scotia, Canada, with a primary diagnosis of HF
      were enrolled in the Improving Cardiovascular Outcomes Study. Two year, all-cause
      mortality was the primary end point. A total of 7816 patients were identified, of
      whom 644 (8%) were discharged home on spironolactone. After adjusting for
      differences in clinical covariates, spironolactone use did not emerge as an
      independent predictor of long-term survival (OR 0.97, P = .80). When only the
      subgroup of patients enrolled in a HF clinic were included (n = 990),
      spironolactone use was associated with reduced rates of all-cause mortality at 2
      years (OR 0.52, P = .003). CONCLUSIONS: Although spironolactone use was not
      associated with improved long-term survival in the general HF population, it was
      associated with improved long-term survival in patients enrolled in HF clinics.
      These data highlight the challenges of knowledge translation from a clinical
      trial into practice.

PMID- 17448413
TI  - Spironolactone reduced arrhythmia and maintained magnesium homeostasis in
      patients with congestive heart failure.
AB  - BACKGROUND: Patients with congestive heart failure (CHF) often have increased
      aldosterone activity that leads to hypomagnesemia. Hypomagnesemia can induce
      arrhythmias, an important cause of death in patients with CHF. We determined
      whether the aldosterone receptor antagonist spironolactone improved magnesium
      homeostasis and reduced arrhythmias in patients with CHF. METHODS AND RESULTS: We
      randomized 116 consecutive patients with CHF into placebo control group (n = 58)
      and spironolactone group (20 mg daily, n = 58) in addition to conventional
      therapy. Plasma magnesium concentration (PMC), erythrocyte magnesium
      concentration (EMC), and erythrocyte magnesium efflux were not different between
      the 2 groups of patients before treatment. Compared with control patients,
      patients treated with spironolactone for 6 months had increased PMC and EMC and
      decreased erythrocyte magnesium efflux. Patients on spironolactone therapy also
      had a marked decrease of 24-hour mean heart rate, ventricular and atrial
      premature beats, and the risk of atrial fibrillation/flutter. Pooled data from
      the 116 patients showed that patients with a higher EMC or a lower sodium
      dependent erythrocyte magnesium efflux had a slower heart rate, fewer ventricular
      premature beats, and a lower risk of atrial fibrillation/flutter. CONCLUSIONS:
      Our results suggest that reducing cellular magnesium efflux and loss may
      contribute to the spironolactone-reduced arrhythmias in patients with CHF.

PMID- 17448414
TI  - Clinical efficacy of surgical heart failure therapy by ventricular restoration
      and restrictive mitral annuloplasty.
AB  - BACKGROUND: Treatment of heart failure by advanced surgical procedures such as
      ventricular restoration (SVR) and restrictive mitral annuloplasty (RMA) is
      increasingly applied. We studied clinical efficacy of heart failure surgery in
      patients with severe heart failure. METHODS AND RESULTS: Thirty-three patients
      (New York Heart Association (NYHA) class III/IV, left ventricular ejection
      fraction < or =35%) were included. Patients with moderate to severe mitral
      regurgitation underwent RMA (85%) and patients with anteroseptal aneurysm
      underwent SVR (52%). A combined procedure was performed in 12 patients, and
      additional coronary artery bypass grafting in 27 patients. Clinical and
      echocardiographic parameters were assessed at baseline and 6 months after
      surgery. Operative mortality was 3% (n = 1), in-hospital mortality was 9% (n =
      3), and there was no late mortality. All clinical parameters were significantly
      improved at 6 months' follow-up (P < .001); NYHA class improved from 3.4 +/- 0.5
      to 1.5 +/- 0.5, Quality-of-life score improved from 44 +/- 22 to 16 +/- 12, and 6
      minute walking distance increased from 248 +/- 134 m to 422 +/- 113 m. Left
      ventricular end-diastolic volume decreased from 107 +/- 32 to 80 +/- 20 mL/m(2)
      (P < .001) and end-systolic volume decreased from 78 +/- 32 to 53 +/- 15 mL/m(2)
      (P < .001), whereas ejection fraction improved from 29 +/- 9 to 35 +/- 7% (P <
      .01). CONCLUSIONS: Surgical treatment of severe heart failure by SVR or RMA was
      associated with 12% mortality at 6 months. Surviving patients showed highly
      significant functional and clinical improvements.

PMID- 17448415
TI  - B-type natriuretic peptide and its molecular precursor in myocardial infarction
      complicated by cardiogenic shock.
AB  - BACKGROUND: Plasma measurement of cardiac natriuretic peptides and their
      biosynthetic precursors is helpful in chronic heart failure patients. In
      contrast, information on circulating B-type natriuretic peptide (BNP) and its
      molecular precursor (proBNP) in patients with cardiogenic shock is scarce. We
      therefore examined proBNP-derived peptides in plasma from patients with
      myocardial infarction complicated by cardiogenic shock. METHODS AND RESULTS:
      Patients were referred for early, invasive therapy because of myocardial
      infarction complicated by cardiogenic shock (n = 13). Plasma proBNP was measured
      with an automated assay (NT-proBNP) and an in-house radioimmunoassay (proBNP);
      BNP concentrations were quantitated with an immunoradiometric assay. The median
      NT-proBNP concentration was 8.2-fold higher than the corresponding BNP
      concentration (873 pmol/L [range 41-12,486] versus 107 pmol/L [1-1041], P <
      .001). Moreover, the NT-proBNP concentration was 3.3-fold higher compared with
      proBNP (268 pmol/L [19-12,220], P < .01). Despite the molar differences, there
      was a strong correlation between NT-proBNP and proBNP (r = 0.84, P < .0001) and
      BNP (r = 0.82, P < .0001) concentrations. Gel filtration chromatography suggested
      that the proBNP immunoreactivity reflect a molecular form larger than the N
      terminal 1-76 fragment. CONCLUSIONS: The study reveals the plasma profile of
      proBNP-derived peptides during myocardial infarction complicated by cardiogenic
      shock. Peripheral concentrations of NT-proBNP, proBNP, and BNP were highly
      correlated despite marked differences between assays. The results also suggest an
      increase in cardiac proBNP processing after myocardial infarction and cardiogenic
      shock.

PMID- 17448416
TI  - Predictors of delivery of hospital-based heart failure patient education: a
      report from OPTIMIZE-HF.
AB  - BACKGROUND: Although recent heart failure (HF) management guidelines recommend
      delivery of patient education and discharge instructions, little is known about
      predictors of delivery of these materials or how such materials relate to
      outpatient disposition postdischarge. This report assesses the degree to which
      the full set of HF discharge instructions and education comprising the Joint
      Commission on Accreditation of Healthcare Organizations process-of-care measure
      (HF-1) was provided, identifies factors predictive of use of HF-1, and determines
      if HF-1 predicts postdischarge outcome disposition in a registry and performance
      improvement (PI) program for patients hospitalized for HF. METHODS AND RESULTS:
      In the Organized Program to Initiate Lifesaving Treatment in Hospitalized
      Patients with Heart Failure (ie, OPTIMIZE-HF), of 33,681 patients from 259 US
      hospitals, 54% received HF-1. Some patient and site characteristics, such as
      symptoms on admission and performance of coronary angiography, were positively
      associated with delivery of the full set of HF-1 components, and others, such as
      African-American or Hispanic race and Midwest site location, were negatively
      associated with HF-1 delivery. However, delivery of the full set of HF-1
      components was significantly more likely in the 46% of patients receiving PI
      tools (OR 2.23, 95% CI 2.12-2.35; P < .0001). Delivery of the full set of HF-1
      components was significantly associated with use of specialty referral programs
      after discharge (P < .0001). CONCLUSIONS: Despite recommendations that complete
      instructions be given to patients with HF before hospital discharge, both PI
      tools to facilitate HF-1 and HF-1 itself are underused. Efforts should focus on
      strengthening processes and structures that will improve consistent delivery of
      HF-1 to all patients.

PMID- 17448417
TI  - High serum level of pentosidine, an advanced glycation end product (AGE), is a
      risk factor of patients with heart failure.
AB  - BACKGROUND: Pentosidine, one of the advanced glycation end products (AGE), is
      generated by nonenzymatic glycation and oxidation of proteins. The receptor of
      AGE (RAGE) is expressed in a variety of tissue, and interaction of AGE with RAGE
      induces oxidative stress and activation of intracellular signaling, causing
      production of cytokines and mediators of inflammation. We investigated whether
      serum pentosidine is a risk factor for heart failure. METHODS AND RESULTS: Serum
      pentosidine concentration was measured in 141 patients with heart failure and 18
      control subjects by a competitive enzyme-linked immunosorbent assay. Patients
      were prospectively followed during a median follow-up period of 479 days with end
      points of cardiac death or rehospitalization. Serum concentration of pentosidine
      was significantly higher in New York Heart Association (NYHA) Class III/IV
      patients than in NYHA class I/II patients (P < .0001). Serum pentosidine was also
      higher in patients with cardiac events than in event-free patients (P < .001). In
      the univariate Cox proportional hazard analysis, age, NYHA class, pentosidine,
      creatinine, uric acid, B-type natriuretic peptide, left ventricular end-systolic
      volume, and left ventricular mass were significant risk factors to predict
      cardiac events. In the multivariate Cox analysis, serum pentosidine concentration
      was an independent risk factor for cardiac events (hazard ratio 1.88, 95%
      confidence interval 1.23-2.69, P = .002). The highest 4th quartile of pentosidine
      was associated with the highest risk of cardiac events (4.52-fold). CONCLUSIONS:
      Serum pentosidine concentration is an independent prognostic factor for heart
      failure, and this new marker may be useful for risk stratification of patients
      with heart failure. Patients were divided into 4 groups based on the serum
      pentosidine levels.

PMID- 17448418
TI  - Relation of inflammatory status to major adverse cardiac events and reverse
      remodeling in patients undergoing cardiac resynchronization therapy.
AB  - BACKGROUND: Inflammatory markers are involved in heart failure (HF)
      pathophysiology. However, the link between these markers and reverse remodeling
      as well as major adverse cardiac events (HF death, sudden death, and unplanned
      cardiac rehospitalizations) in patients who undergo cardiac resynchronization
      therapy (CRT) has not been evaluated. METHODS AND RESULTS: We recorded major
      adverse cardiac events of 140 patients (on optimized medical therapy, left
      ventricular ejection fraction 29.9 +/- 9.6%, New York Heart Association Class III
      IV, with intraventricular dyssynchrony) who underwent CRT (enrolled since April
      2004). Moreover, we evaluated before and after 6 months of CRT: interleukin-6,
      high-sensitivity C-reactive protein, New York Heart Association class, quality of
      life (score on Minnesota Living with Heart Failure questionnaire), 6-minute
      walking test, left ventricular end-diastolic and end-systolic volumes (nonindexed
      and indexed by body surface area), and left ventricular ejection fraction.
      Adverse cardiac events were observed in 40 patients (28.6%): 22 deaths and 18
      cardiac unplanned rehospitalizations. Only patients without adverse events during
      follow-up showed a significant reduction of inflammatory markers and left
      ventricular volumes (reverse remodeling), despite a significant improvement of
      clinical status observed in both groups of patients. CONCLUSIONS: The reduction
      of inflammatory status seems to be linked to reverse remodeling as well as to a
      better clinical prognosis in patients with HF who underwent CRT.

PMID- 17448419
TI  - Disappearance of left ventricular hypertrabeculation/noncompaction after
      biventricular pacing in a patient with polyneuropathy.
AB  - BACKGROUND: Disappearance of left ventricular hypertrabeculation/noncompaction
      (LVHT) has been reported only in myocarditis. We report disappearance of LVHT
      after implantation of a biventricular pacemaker in a 68-year-old female. She
      suffered from symmetrical polyneuropathy and heart failure New York Heart
      Association Class IV due to dilated cardiomyopathy despite angiotensin-converting
      enzyme inhibitors, beta-blockers, digitalis, and diuretics.
      Echocardiographically, she showed an enlarged poorly contracting left ventricle
      with LVHT involving the lateral and apical wall. METHODS AND RESULTS: In January
      2001, a biventricular pacemaker system was implanted. From that time, her
      condition and left ventricular systolic function improved and the left
      ventricular size decreased. Surprisingly, LVHT could no longer be detected
      echocardiographically. CONCLUSIONS: We explain LVHT disappearance as follows: (1)
      the trabeculations are still existing, but not visible any more because of the
      better contraction state of the left ventricle; (2) the trabeculations have
      regressed because they are not needed anymore; and (3) the trabeculations have
      been falsely diagnosed and were in fact ventricular thrombi, which is quite
      unlikely because no embolic events occurred. LVHT can disappear if dilatation of
      the cardiac cavities and severely reduced systolic function regress. The dynamics
      of LVHT may represent an adaption mechanism of the cardiac function to compensate
      for a temporary failing myocardium.

PMID- 17448420
TI  - The emerging role of multi-detector computed tomography in heart failure.
AB  - BACKGROUND: Recent advances in cardiac multi-detector computed tomography (MDCT)
      technology now permits entire coronary tree evaluation in a single breath hold
      with submillimeter slice collimation and improved temporal resolution. METHODS
      AND RESULTS: Besides excellent correlation with invasive angiogram for the
      detection of significant coronary occlusion, MDCT also provides reliable and
      reproducible data regarding various other cardiac anatomic and functional
      parameters that are pertinent to heart failure patients. These include left
      ventricular measurement (eg, ejection fraction, regional wall motion, dimensions,
      volumes), pulmonary vein anatomy and drainage, right ventricular function, and
      cardiac venous system, among many others. However, there are radiogenic and
      nonradiogenic risks associated with MDCT that should be considered before
      scanning the patients. CONCLUSIONS: This review summarizes the existing
      literature of the various cardiac MDCT applications pertinent to heart failure
      patients.

PMID- 17448421
TI  - Decompensation of chronic heart failure associated with pregabalin in patients
      with neuropathic pain.

PMID- 17448422
TI  - In vivo effects of myocardial creatine depletion on left ventricular function,
      morphology, and energy metabolism--consequences in acute myocardial infarction.
AB  - BACKGROUND: The failing heart is characterized by disturbed myocardial energy
      metabolism and creatine (Cr) depletion. The aims of this study were to in vivo
      evaluate the effects of Cr depletion on: a) left ventricular (LV) function and
      morphology during rest and stress, b) LV energy metabolism, c) catecholamine in
      LV and plasma content, and d) incidence of malignant ventricular arrhythmias
      (MVA) during acute myocardial infarction (MI). METHODS AND RESULTS: Male rats
      weighing approximately 200 g were used. Two groups were studied: the rats treated
      with Cr analogue beta-guanidinopropionic acid (BGP) (n = 25) and controls (n =
      23). BGP (1 M) was administered by subcutaneously implanted osmotic minipumps
      over 4 weeks. The rats (BGP n = 9, control n = 12) were than examined with
      transthoracic echocardiography at basal and at stress conditions induced by
      transesophageal pacing. In vivo (31)P magnetic resonance spectroscopy (MRS) was
      used for evaluation of myocardial energy status (BGP n = 7, control n = 12).
      (31)P MRS, echocardiography and high-performance liquid chromatography analysis
      of myocardial Cr, total adenine nucleotides and catecholamines in myocardium and
      plasma were performed on noninfarcted hearts. Myocardial infarction was induced
      in a subgroup of animals (BGP n = 15, control n = 15) by ligation of the left
      coronary artery resulting in a large ( approximately 50%) anterolateral MI and
      acute HF. A computerized electrocardiogram tracing was obtained continuously
      before induction of MI and up to 60 minutes postinfarction. Qualitative and
      quantitative variables of ventricular arrhythmias were analyzed using arrhythmia
      score. Body weight (BW) was lower (P < .01), whereas LV/BW was higher (P < .01)
      in the BGP group. Total myocardial Cr pool was decreased for at least 50% (P <
      .01) compared with the controls. There was no difference in total nucleotide
      pool. Phosphocreatine/adenosine-3-phosphate ratio was lower in the BGP group (P <
      .01). LV systolic function was disturbed during rest and stress (P < .05).
      Similarly, LV dimensions were increased in the BGP group (P < .05). Induction of
      acute MI resulted in markedly increased incidence of MVA and higher mortality in
      the BGP group (P < .01). CONCLUSIONS: Myocardial Cr depletion results in
      functional and structural LV alterations associated with lower myocardial energy
      reserve. Intact myocardial Cr metabolism is important for normal LV function
      during basal and stress conditions. Acute MI in the setting of myocardial Cr
      depletion leads to excessive mortality from ventricular arrhythmias and
      progressive heart failure.

PMID- 17448423
TI  - Hydralazine and nitrates: beyond race and ethnicity.

PMID- 17448424
TI  - Mister Rogers' neighborhood...

PMID- 17448426
TI  - The epidemiology of valvular heart disease: a growing public health problem.

PMID- 17448427
TI  - Role of statins in aortic valve disease.

PMID- 17448428
TI  - Cellular and molecular basis of remodeling in valvular heart diseases.

PMID- 17448429
TI  - Assessment of mitral regurgitation and clinical decision-making.

PMID- 17448430
TI  - Aortic stenosis: from pressure overload to heart failure.

PMID- 17448431
TI  - Left ventricular dysfunction and mitral stenosis.

PMID- 17448432
TI  - Hemodynamic characteristics and progression to heart failure in regurgitant
      lesions.

PMID- 17448433
TI  - Optimal timing of surgery in aortic regurgitation.

PMID- 17448434
TI  - Regurgitant lesions of the aortic and mitral valves: considerations in
      determining the ideal timing of surgical intervention.

PMID- 17448435
TI  - On some relations between advancing, receding and Young's contact angles.
AB  - Problems of experimental determination and theoretical verification of
      equilibrium contact angles are discussed basing on the literature data. A
      relationship between the advancing and receding contact angles versus the
      equilibrium contact angle is described and then verified using the literature
      contact angles determined on paraffin wax and polypropylene. Using the proposed
      relationship and experimentally determined equilibrium contact angles, obtained
      by plotting the advancing and receding contact angles versus the contact angle
      hysteresis or by applying vibration of the system liquid drop/solid surface, it
      is found that the same value of the surface free energy for paraffin wax is
      calculated from the contact angles of water and ethylene glycol. However, in the
      case of polypropylene some inconsistency appears between the equilibrium contact
      angles of the probe liquid used and the calculated surface free energy. More
      experimental data of the equilibrium contact angle are needed to verify further
      the relationship.

PMID- 17448437
TI  - Cognitive mismatches in the cockpit: will they ever be a thing of the past?
AB  - Changes in aviation over the last 30 years have dramatically affected the way
      that flight crews fly aircraft. The implementation and evolution of the glass
      cockpit, however, has happened in an almost ad hoc fashion, meaning that it does
      not always properly support the flight crew in carrying out their tasks. In such
      situations, the crew's mental model of what is happening does not always match
      the real state of affairs. In other words, there is a cognitive mismatch. An
      initial taxonomy of cognitive mismatches is defined, and the problem illustrated
      using an example from an aviation accident. Consideration is then given to how
      cognitive mismatches can be managed. A call is made for the development of an
      integrated cockpit architecture that takes better account of human capabilities
      and allows for new developments to be added to the cockpit in a more seamless
      manner.

PMID- 17448436
TI  - An ImmunoChip prototype for simultaneous detection of antiepileptic drugs using
      an enhanced one-step homogeneous immunoassay.
AB  - The development and characterization of a one-step homogeneous immunoassay-based
      multiwell ImmunoChip is reported for the simultaneous detection and quantitation
      of antiepileptic drugs (AEDs). The assay platform uses a cloned enzyme donor
      immunoassay (CEDIA) and a Beta-Glo assay system for generation of bioluminescent
      signal. Results of the one-step CEDIA for three AEDs (carbamazepine, phenytoin,
      and valproic acid), in the presence of serum, correlate well with the values
      determined by fluorescence polarization immunoassay. CEDIA intra- and interassay
      coefficients of variation are less than 10%. A microfabrication process,
      xurography, was used to produce the multiwell ImmunoChip. Assay reagents were
      dispensed and lyophilized in a three-layer pattern. The multiwell ImmunoChip
      prototype was used to detect and quantify AEDs in serum samples containing all
      three drugs. Luminescent signals generated from each well were recorded with a
      charge-coupled device (CCD) camera. The assays performed on an ImmunoChip were
      fast (5 min), requiring only small volumes of both the reagents (<1 microl/well)
      and the serum sample. The ImmunoChip assay platform described in this article may
      be well suited for therapeutic monitoring of drugs and metabolites at the point
      of-care setting.

PMID- 17448438
TI  - Superior head of human lateral pterygoid muscle: single motor unit firing rates
      during isometric force.
AB  - The superior head of the human lateral pterygoid muscle (SHLP) has been
      classically considered to have functions that are independent of the inferior
      head of the lateral pterygoid (IHLP). Recent evidence however suggests that some
      of the functional properties of the SHLP are similar to those of the IHLP. The
      aim was to determine whether the functional properties in terms of single motor
      unit (SMU) firing rates within the SHLP vary with horizontal isometric force (400
      800gwt) and direction (i.e., contralateral (CL), protrusive (P), ipsilateral (IL)
      and intermediate directions, CL-P, IL-P) in a manner similar to those identified
      for the IHLP, and as would be expected if both SHLP and IHLP should be regarded
      as one muscle. In eight subjects, the firing rates of 40 SMUs were recorded from
      computer tomography (CT)-verified SHLP sites while each subject exerted
      horizontal isometric forces with their lower jaw onto a force transducer in the
      five directions. Firing rates increased significantly with horizontal isometric
      force from 400 to 800gwt. Firing rates also changed significantly (p<0.01) with
      direction with CL, CL-P and P having comparable firing rates (13.3, 12.6 and
      12.6impulses/s, respectively) which were significantly higher than IL-P. The
      similarity of these data to previous IHLP data, provide additional support for
      the hypothesis that the SHLP and the IHLP should be regarded as two parts of one
      muscle.

PMID- 17448439
TI  - Fluorescence induction in the phycobilisome-containing cyanobacterium
      Synechococcus sp PCC 7942: analysis of the slow fluorescence transient.
AB  - At room temperature, the chlorophyll (Chl) a fluorescence induction (FI) kinetics
      of plants, algae and cyanobacteria go through two maxima, P at approximately 0.2
      1 and M at approximately 100-500 s, with a minimum S at approximately 2-10 s in
      between. Thus, the whole FI kinetic pattern comprises a fast OPS transient (with
      O denoting origin) and a slower SMT transient (with T denoting terminal state).
      Here, we examined the phenomenology and the etiology of the SMT transient of the
      phycobilisome (PBS)-containing cyanobacterium Synechococcus sp PCC 7942 by
      modifying PBS-->Photosystem (PS) II excitation transfer indirectly, either by
      blocking or by maximizing the PBS-->PS I excitation transfer. Blocking the PBS-
      >PS I excitation transfer route with N-ethyl-maleimide [NEM; A. N. Glazer, Y.
      Gindt, C. F. Chan, and K.Sauer, Photosynth. Research 40 (1994) 167-173] increases
      both the PBS excitation share of PS II and Chl a fluorescence. Maximizing it, on
      the other hand, by suspending cyanobacterial cells in hyper-osmotic media [G. C.
      Papageorgiou, A. Alygizaki-Zorba, Biochim. Biophys. Acta 1335 (1997) 1-4]
      diminishes both the PBS excitation share of PS II and Chl a fluorescence. Here,
      we show for the first time that, in either case, the slow SMT transient of FI
      disappears and is replaced by continuous P-->T fluorescence decay, reminiscent of
      the typical P-->T fluorescence decay of higher plants and algae. A similar P-->T
      decay was also displayed by DCMU-treated Synechococcus cells at 2 degrees C. To
      interpret this phenomenology, we assume that after dark adaptation cyanobacteria
      exist in a low fluorescence state (state 2) and transit to a high fluorescence
      state (state 1) when, upon light acclimation, PS I is forced to run faster than
      PS II. In these organisms, a state 2-->1 fluorescence increase plus electron
      transport-dependent dequenching processes dominate the SM rise and maximal
      fluorescence output is at M which lies above the P maximum of the fast FI
      transient. In contrast, dark-adapted plants and algae exist in state 1 and upon
      illumination they display an extended P-->T decay that sometimes is interrupted
      by a shallow SMT transient, with M below P. This decay is dominated by a state 1-
      >2 fluorescence lowering, as well as by electron transport-dependent quenching
      processes. When the regulation of the PBS-->PS I electronic excitation transfer
      is eliminated (as for example in hyper-osmotic suspensions, after NEM treatment
      and at low temperature), the FI pattern of Synechococcus becomes plant-like.

PMID- 17448440
TI  - Characterization of a subcomplex of mitochondrial NADH:ubiquinone oxidoreductase
      (complex I) lacking the flavoprotein part of the N-module.
AB  - Mitochondrial NADH:ubiquinone oxidoreductase is the largest and most complicated
      proton pump of the respiratory chain. Here we report the preparation and
      characterization of a subcomplex of complex I selectively lacking the
      flavoprotein part of the N-module. Removing the 51-kDa and the 24-kDa subunit
      resulted in loss of catalytic activity. The redox centers of the subcomplex could
      be reduced neither by NADH nor NADPH demonstrating that physiological electron
      input into complex I occurred exclusively via the N-module and that the NADPH
      binding site in the 39-kDa subunit and further potential nucleotide binding sites
      are isolated from the electron transfer pathway within the enzyme. Taking
      advantage of the selective removal of two of the eight iron-sulfur clusters of
      complex I and providing additional evidence by redox titration and site-directed
      mutagenesis, we could for the first time unambiguously assign cluster N1 of
      fungal complex I to mammalian cluster N1b.

PMID- 17448441
TI  - Inhibition of fear acquisition in toddlers following positive modelling by their
      mothers.
AB  - The present study used an experimental design to investigate the role of
      modelling as a protective factor in fear and avoidance learning in a sample of 77
      toddlers. Mothers and their 12-20-month-old children were randomly assigned to
      one of three pre-exposure conditions: (1) a modelling group (n=27) observed their
      mothers responding positively to a fear-relevant stimulus; (2) a stimulus-only
      group (n=25) were exposed to a fear-relevant stimulus alone; and (3) a control
      group (n=25) were exposed to neither modelling nor the stimulus alone. Children
      in all three groups were then subjected to an observational conditioning trial in
      which the experimenter reacted with fear and disgust toward the stimulus. When
      subsequently tested for the acquisition of fear, children in the modelling group
      showed more positive affective reactions and more approach behaviours than either
      controls or children exposed to the stimulus alone. The results demonstrate that
      very young children can rapidly form lasting associations between maternal
      affective reactions and novel, fear-relevant stimuli. Further, positive maternal
      reactions to a stimulus can over-ride any fear-evoking effect of negative
      reactions to that stimulus by a stranger.

PMID- 17448442
TI  - Implicit associations between smoking and social consequences among smokers in
      cessation treatment.
AB  - Explicit expectations of the negative and positive social consequences of smoking
      are likely to have substantial influence on decisions regarding smoking. However,
      among smokers trying to quit, success in smoking cessation may be related not
      only to the content of expectancies about smoking's social effects but also to
      the ease with which these cognitive contents come to mind when confronted with
      smoking stimuli. To examine this possibility, we used the implicit association
      test (IAT) [Greenwald, A. G., McGhee, D. E., & Schwartz, J. L. K. (1998).
      Measuring individual differences in implicit cognition: The implicit association
      test. Journal of Personality and Social Psychology, 74, 1464-1480] to assess
      implicit cognitive associations between smoking and negative vs. positive social
      consequences among 67 heavy social drinkers seeking smoking cessation treatment
      in a randomized clinical trial. Results showed that the relative strength of
      implicit, negative, social associations with smoking at baseline predicted higher
      odds of smoking abstinence during treatment over and above the effects of
      relevant explicit measures. The only variable that significantly correlated with
      IAT scores was the density of smokers in participants' social environment; those
      with more smoking in their social environment showed weaker negative social
      associations with smoking. Results suggest implicit cognition regarding the
      social consequences of smoking may be a relevant predictor of smoking cessation
      outcome.

PMID- 17448443
TI  - Identification of dermcidin in human gestational tissue and characterization of
      its proteolytic activity.
AB  - Dermcidin (DCD) is a gene for an antimicrobial peptide DCD-1 in human sweat
      glands. It has become evident that the gene products of DCD exhibit a wide range
      of biological functions. In addition to its antimicrobial function, it is
      reported to be a neuronal survival factor, a putative oncogene in breast cancer
      and a proteolysis-inducing factor (PIF) that induces skeletal muscle proteolysis
      to cause cancer cachexia. Here we identified DCD in human placental tissue and
      determined its previously uncharacterized proteolytic activity. We also show that
      recombinant DCD induced an invasive phenotype in a human choriocarcinoma cell
      line JAR in vitro. This work suggests that DCD might participate in the
      regulation of placental function by means of modulating the proteolytic cascades
      on the trophoblastic cell surface, and might be involved in the pathophysiology
      of pregnancy-related disorders, as well as cancer and neuronal diseases.

PMID- 17448444
TI  - Bile acids and lipoprotein metabolism: effects of cholestyramine and
      chenodeoxycholic acid on human hepatic mRNA expression.
AB  - Modulation of bile acid synthesis in human by cholestyramine or by
      chenodeoxycholic acid (CDCA) treatment affects lipoprotein metabolism leading to
      altered plasma lipid levels. The molecular changes caused by these treatments,
      which in turn influence lipoprotein metabolism, are still not entirely known in
      humans. In this study, mRNA levels were analyzed using real time RT-PCR in liver
      tissue from patients undergoing cholecystectomy due to gallstone disease. The
      patients were treated with either CDCA (n=6) or cholestyramine (n=5) for three
      weeks prior to surgery, six patients received no treatment and served as
      controls. Cholestyramine increased the expression of the LDL receptor (LDLR) by
      about 65% and that of proprotein convertase subtilisin kexin 9 (PCSK9) by 70%.
      After CDCA the levels of both LDLR and hydroxy-methyl-glutaryl coenzyme A
      reductase mRNA decreased approximately by 50%. The expression of PCSK9 was not
      changed. The mRNA levels of PCSK9, LDLR, and HMGCoAR were significantly
      correlated to those of sterol regulatory element binding protein 2 (SREBP2),
      indicating that SREBP2 is of importance in the regulation of the expression of
      these genes also in human liver.

PMID- 17448445
TI  - D-box is required for the degradation of human Shugoshin and chromosome
      alignment.
AB  - Chromosome segregation and proper alignment in mitosis relies on cohesion between
      sister chromatids and the interaction of the kinetochore with spindle
      microtubules. Vertebrate Sgo 1 localizes to kinetochores and is required to
      prevent premature sister centromere separation in mitosis. Sgo 1 is degraded by
      the anaphase-promoting complex, allowing the separation of sister centromeres in
      anaphase. However, little is known about the molecular basis of Sgo 1 degradation
      and its temporal control during mitosis. Here, we show that APC/C targets human
      Sgo 1 for degradation through a destruction box motif (D-box) in its C-terminus.
      Mutation in the D-box causes transient metaphase arrest, and mutation in the D
      box leads to defects in chromosome alignment and segregation through its effect
      on the localization of Aurora B and CENP-E. These results provide a link between
      sister centromere cohesion and bipolar attachment of kinetochores.

PMID- 17448446
TI  - Characterization of Rab45/RASEF containing EF-hand domain and a coiled-coil motif
      as a self-associating GTPase.
AB  - Rab-family GTPases function as key regulators for membrane traffic. Among them,
      Rab45/RASEF is an atypical GTPase in that it contains a coiled-coil motif at the
      mid region and a distinct N-terminal EF-hand domain with C-terminal Rab-homology
      domain. Here, we provide the initial biochemical characterization and
      intracellular localization of human Rab45. Rab45 bound guanine nucleotide tri-
      and di-phosphates through the C-terminal Rab domain. Rab45 was capable of self
      interacting, and the self-interaction required the mid region containing the
      coiled-coil motif. Rab45 expressed in HeLa cells was localized in a small patch
      in the perinuclear area of the cell, and the localization was regulated by the
      guanine nucleotide-bound states of Rab45. Interestingly, the mid region, together
      with Rab domain, appeared to be essential for the characteristic perinuclear
      localization of Rab45, indicating that the self-interaction may be involved in
      the intracellular localization of Rab45.

PMID- 17448447
TI  - Live imaging of spindle pole disorganization in docetaxel-treated multicolor
      cells.
AB  - Treatment of cells with docetaxel at low concentrations induces aberrant bipolar
      spindles of which two centrosomes stay at only one pole, and also induces
      multipolar spindles. To gain insight into the relations between centrosome
      impairment and structural defects of the spindle, live-cell imaging was performed
      on a human MDA Auro/imp/H3 cell line in which centrosomes/mitotic spindles,
      nuclear membrane and chromatin were simultaneously visualized by fluorescent
      proteins. In the presence of docetaxel at IC(50) concentration, the centrosomes
      did not segregate, and multiple aster-like structures ectopically arose around
      the disappearing nuclear membrane. Those ectopic structures formed an
      acentrosomal pole opposing to the two-centrosomes-containing pole. In late
      metaphase, one pole often fragmented into multiple spindle poles, leading
      multipolar division. These results suggest that spindle pole fragility may be
      induced by centrosome impairment, and collapse of the pole may contribute to
      induction of aneuploid daughter cells.

PMID- 17448448
TI  - Effect of catechol O-methyltransferase val(158)met polymorphism on the p50 gating
      endophenotype in schizophrenia.
AB  - BACKGROUND: Studies have implicated prefrontal dopamine in cortical information
      filtering. Deficit in stimulus filtering, an endophenotype of schizophrenia, can
      be demonstrated using the auditory P50 paired-click gating paradigm. The role of
      prefrontal dopamine on P50 gating was investigated, using catechol-O
      methyltransferase (COMT) valine (val)(158)methionine (met) polymorphism as a
      predictor of prefrontal dopamine activity. METHODS: Twenty-five comparison and 42
      schizophrenia subjects underwent P50 gating measurement and COMT genotyping.
      RESULTS: In the combined sample, COMT polymorphism accounted for a unique 10% of
      gating variance (p = .02), after variance due to diagnosis, smoking status, and
      antipsychotic use was removed. Valine homozygous individuals exhibited the
      greatest gating deficit. CONCLUSIONS: Valine homozygous individuals are more
      likely to have gating deficits, supporting COMT as a genetic determinant of the
      P50 endophenotype, as well as a role for prefrontal dopamine in auditory
      filtering.

PMID- 17448449
TI  - 5HT2A receptor binding is increased in borderline personality disorder.
AB  - BACKGROUND: Postmortem studies in suicide victims demonstrate an increase in the
      number of post-synaptic 5-HT(2A) receptor binding sites in ventral lateral and
      orbital frontal cortex. Diminished metabolic responses to serotonergic activation
      are noted in these areas in impulsive subjects with borderline personality
      disorder (BPD), a group at high risk for suicidal behaviors. We examined 5HT(2A)
      receptor binding potential (BP) in impulsive subjects with BPD, with positron
      emission tomography neuroimaging with [(18)F] altanserin. METHODS: Fourteen
      female subjects with BPD were assessed for Axis I comorbidity, depressed mood,
      impulsivity, aggression, suicidality, childhood abuse, and compared with 11
      healthy female control subjects. The 5HT(2A) receptor binding was evaluated in
      prefrontal cortex, anterior cingulate, hippocampus, temporal lobe, occipital
      cortex, and thalamus. Data were analyzed with Logan graphical analysis and a four
      compartment (4C) model. RESULTS: Hippocampal 5HT(2A) receptor binding was
      significantly increased in BPD subjects compared with control subjects in both
      Logan and 4C analyses, covarying for age. Hippocampal BP values were related to
      comorbid major depressive episode, with highest values found in non-depressed BPD
      subjects and lowest in healthy control subjects. The BP values were not related
      to depressed mood, impulsivity, aggression, suicidality, or childhood abuse.
      CONCLUSIONS: 5HT(2A) receptor binding is increased in the hippocampus of BPD
      subjects independent of depressed mood, impulsivity, aggression, suicidality, or
      childhood abuse. Dysregulation of serotonergic function in hippocampus might
      contribute to affective and behavioral symptoms in BPD.

PMID- 17448450
TI  - The influence of olfactory-induced negative emotion on verbal working memory:
      individual differences in neurobehavioral findings.
AB  - The influence of emotion on cognition plays an important role in people's
      everyday life as well as in psychiatric and neurological disorders. The present
      study used fMRI to examine the neural correlates of cognitive-emotional
      interactions and its inter-individual differences. Twenty-one healthy males
      performed a 0-back/2-back task while negative or neutral emotion was induced by
      negative/neutral olfactory stimulation. Subjects revealed a differential effect
      of emotion on cognition; in 9 subjects, negative odor had a deteriorating
      influence on verbal working memory ("affected group", AG) while in 12 subjects,
      performance was not affected in a negative way ("unaffected group", UAG).
      Although no brain activation differences emerged during the working memory task,
      the interaction of working memory and emotion yielded significant differences
      between the AG and the UAG. The latter showed greater activation in the fronto
      parieto-cerebellar working memory (WM) network including the precuneus while the
      AG demonstrated stronger activation in more "emotional" areas (mainly the
      temporal and medial frontal cortex) as well as compensatory activations in
      prefrontal regions known to be essential for the cognitive down-regulation of
      emotions. Hence, the UAG may have been better able to counteract the detrimental
      influence of negative stimulation during the 2-back task and to effectively
      sustain or even increase activation in the task-relevant WM network. Correlation
      analyses for the whole group supported this interpretation; reduced working
      memory performance during negative stimulation was accompanied by higher
      activation in the inferior frontal gyrus whereas less performance impairment was
      related to higher activation in the precuneus. Results confirm the importance of
      incorporating individual differences in emotion processing and its interaction
      with cognitive functions in neuroimaging.

PMID- 17448451
TI  - The use of anesthesia during evoked potential audiometry in goldfish (Carassius
      auratus).
AB  - Auditory-evoked potentials (AEPs) have become a widely utilized measure of
      hearing sensitivity. Most investigators use pharmacological paralysis to reduce
      myogenic noise and immobilize the animal for stable electrical recordings, but
      additional anesthesia is generally not used because the most commonly available
      fish anesthetic, the cholinergic antagonist tricaine methanosulfate (MS222), is
      known to disrupt hair cell and primary afferent physiology. Anesthetic agents
      that do not interfere with auditory function would be a useful adjunct to
      paralytic immobilization and would reduce any possible distress incurred by
      prolonged immobilization. In this report we tested the opiate anesthetic fentanyl
      and compared hearing thresholds in immobilized versus immobilized and
      anesthetized animals. Short-term effects of mild MS222 anesthesia were also
      measured via evoked potential audiometry. Animals were tested before and after
      fentanyl injection (100, 500 and 2500 microg g(-1) fish body-weight) using
      standard evoked potential audiometry. Tone pips, 0.2-3 kHz, from an aerial
      loudspeaker served as stimuli. Fentanyl altered evoked potential waveforms
      slightly but did not alter estimated threshold sensitivity. These results suggest
      fentanyl be considered as a possible addition to AEP techniques in goldfish
      (Carassius auratus) and poikilothermic vertebrates generally.

PMID- 17448452
TI  - The role of the basal ganglia in bimanual coordination.
AB  - The functional anatomical role of the basal ganglia in bimanual coordination is
      unknown. Utilizing functional MRI (fMRI) at 3 T, we analyzed brain activity
      during three different typing tasks. The first task consisted of typing with
      parallel finger movements (moving left to right with four fingers on both hands).
      The second task was mirror movements (moving little finger to index finger on
      both hands), and the third task compared a resting condition with right-handed
      unimanual typing (moving little finger to index finger). Task dependent BOLD
      activity in the supplementary motor area (SMA) and dorsolateral premotor areas
      was observed. In addition, activation patterns were present in the cerebellar
      vermis during bimanual coordination tasks, with greater activation in the
      parallel than in the mirror condition. Finally, we also identified activity in
      the putamen during the tasks described above. Interestingly, putaminal activity
      was greatest during the period of motor task initiation, and activity during this
      period was greatest in the parallel condition. Our results suggest a critical
      role of the basal ganglia in the neural control of bimanual coordination.

PMID- 17448453
TI  - Cardiac epinephrine synthesis and ischemia-induced myocardial epinephrine
      release.
AB  - OBJECTIVE: Phenylethanolamine-N-methyltransferase (PNMT), the enzyme that
      synthesizes epinephrine (EPI) from norepinephrine (NE) in the adrenal gland, is
      present in extra-adrenal tissues including heart. Ischemia evokes an excessive NE
      accumulation in the myocardial interstitial spaces. Therefore, cardiac PNMT
      activity with high NE levels may contribute to cardiac EPI synthesis and release
      evoked by ischemia. METHODS: We measured dialysate EPI levels in the left
      ventricle of anesthetized rabbits using a cardiac microdialysis technique. The
      dialysate EPI level served as an index of the myocardial interstitial EPI level.
      Locally administered NE-induced dialysate EPI responses were measured. The left
      circumflex coronary artery was occluded for 60 min and the dialysate EPI and NE
      levels in the ischemic region were measured. Coronary occlusion-induced EPI
      responses were compared with and without administration of a PNMT inhibitor
      (SKF29661) in the presence and absence of desipramine (catecholamine transport
      blocker). RESULTS: Local administration of NE (250, 2500 ng/ml) increased the EPI
      levels to 734+/-125 and 2088+/-367 pg/ml respectively. These increases in
      dialysate EPI were suppressed by the PNMT inhibitor. Acute myocardial ischemia
      significantly increased the EPI levels to 3607+/-1069 pg/ml in the ischemic
      region, and these were suppressed by the PNMT inhibitor (1417+/-581 pg/ml). The
      pretreatment with desipramine suppressed ischemia-induced EPI release, which did
      not differ with (725+/-155 pg/ml) and without administration of a PNMT inhibitor
      (743+/-172 pg/ml). CONCLUSION: The cardiac PNMT in the left ventricle is capable
      of synthesizing EPI with markedly elevated NE levels in the myocardial
      interstitial space.

PMID- 17448454
TI  - Establishing a neurological-psychiatric biobank: banking, informatics, ethics.
AB  - The recent development of genetic databases and biobanks in a number of countries
      reflects scientist's beliefs in the future health benefits to be derived from
      genetic research. The NEPSYBANK is a national program of the Hungarian Clinical
      Neurogenetic Society with comprehensive participation of the Neurology and
      Psychiatry Departments of Medical Universities and the National Institute of
      Psychiatry and Neurology. The NEPSYBANK forms a part of the national biobank
      project (www.biobank.hu). The goal is to establish nationwide collaboration and
      common biobanking standards on quality, access, and protection of integrity in
      the field of neurology and psychiatry. Biological materials and databases are
      already collected in stroke, epilepsy, multiple sclerosis, motoneuron diseases,
      dementia, movement disorders, schizophrenia, and alcohol addiction. In peripheral
      neuropathies, neuropathic pain syndromes, muscle diseases, migraine, myasthenia
      gravis, depression, panic disease, anxiety, autism, and software development is
      in progress. The resources have been expanded by continued prospective collection
      of samples and data and important bottlenecks in sample purification, sample
      retrieval, in protection of the integrity of the research participants, as well
      as in guaranteeing the security and confidentiality of the participant's
      information have been harmonized. The development of uniform consent management,
      comprehensive sample overview and quality standards for health care-related
      biobanking may provide a unique opportunity for Hungary in molecular clinically
      oriented research. The program is a diseased-based research biobank with
      comprehensive collection of phenotypic and environmental information as well as
      biobanking of DNA, RNA or buffy coat, plasma, and erythrocytes stored at -80
      degrees C. The biobank has a neuropathological part as well: storing conventional
      pathology and biopsy specimens. The analytical and informational demands being
      created by biobanking requires a "connectivity of community" that has not
      traditionally been present in the life sciences. As you put more resources into
      something, your silos tend to become taller, and we need to avoid this. The life
      science and healthcare community should be ignored working in individual "silos."

PMID- 17448455
TI  - The immunobiological development of human bone marrow mesenchymal stem cells in
      the course of neuronal differentiation.
AB  - The central nervous system (CNS) has been referred to as the "immunological
      privileged site". However, it is now clear that the privileged status of the CNS
      is a result of a balance between immune privilege and effective response. In
      vitro, human bone marrow mesenchymal stem cells (MSCs) have the ability to
      differentiate into neurons. Based on this biological attribute we gain the
      possibility by means of using MSCs as the donors to develop a future cell therapy
      in clinical application. But using MSCs as donor cells inevitably raises the
      question as to whether these donor cells would be immunogenic, and if so, would
      they be rejected after transplantation. To investigate this, human MSCs were
      cultured in vitro and induced to differentiate along neuronal lineage. The
      expression of human leukocyte antigen (HLA) class I and class II molecules and
      the co-stimulatory protein CD80 were increased on the surface of MSCs in the
      course of neuronal differentiation. But neither of the co-stimulatory proteins,
      CD40 or CD86, was expressed. After IFN-gamma exposure, the expression of the HLA
      molecules was further enhanced, but the co-stimulatory proteins were unaffected.
      MSCs that had been differentiated along neuronal lineage were not capable of
      inducing the proliferation of peripheral blood lymphocytes (PBLs). Even after IFN
      gamma exposure, PBLs remained unresponsive. Furthermore, MSCs differentiated
      along neuronal lineage suppressed the proliferation of PBLs induced by allogeneic
      PBLs and mitogens. The mechanisms involved in the immunosuppression may be
      related to the effect of soluble factors and cell-cell interactions of neuronal
      differentiated MSCs and PBLs. From the above data we suggested that the low
      immunogenicity and immunomodulatory function of MSCs in the course of neuronal
      differentiation in vitro, which will be helpful to further investigation in order
      to establish the new way for future medical application.

PMID- 17448456
TI  - Antimitotic activity of methoxyconidiol, a meroterpene isolated from an ascidian.
AB  - Methoxyconidiol is a meroterpene previously extracted from the ascidian Aplidium
      aff. densum [A. Simon-Levert, A. Arrault, N. Bontemps-Subielos, C. Canal, B.
      Banaigs. Meroterpenes from the ascidian Aplidium aff. densum, J. Nat. Prod. 68
      (2005) 1412-1415]. In the present work we investigated its antimitotic effect on
      eukaryotic cells by using a bioassay based on the sea urchin early embryo. This
      bioassay has been successfully used to evaluate the efficacy of antiproliferative
      agents and to rapidly determine the affected cell cycle phase. We demonstrated
      that methoxyconidiol inhibits the cleavages of sea urchin Sphaerechinus
      granularis and Paracentrotus lividus fertilized eggs. This meroterpene disrupts M
      phase progression and completely blocks cytokinesis without having any effect on
      DNA replication. The treatment severely disturbs the establishment of a mitotic
      spindle, most likely by affecting microtubule dynamics. Moreover, while the cell
      cycle regulatory kinase cyclin B/CDK1 is activated, cyclin B proteolysis is
      inhibited, impeding the output of M-phase. This characteristic cell cycle arrest
      induced by methoxyconidiol in sea urchin eggs emphasizes the interest for this
      drug as a putative antiproliferative agent for tumor cells.

PMID- 17448457
TI  - The MAPK(ERK-1,2) pathway integrates distinct and antagonistic signals from
      TGFalpha and FGF7 in morphogenesis of mouse mammary epithelium.
AB  - Transforming growth factor-alpha (TGFalpha) and fibroblast growth factor-7 (FGF7)
      exhibit distinct expression patterns in the mammary gland. Both factors signal
      through mitogen-activated kinase/extracellular regulated kinase-1,2
      (MAPK(ERK1,2)); however, their unique and/or combined contributions to mammary
      morphogenesis have not been examined. In ex vivo mammary explants, we show that a
      sustained activation of MAPK(ERK1,2) for 1 h, induced by TGFalpha, was necessary
      and sufficient to initiate branching morphogenesis, whereas a transient
      activation (15 min) of MAPK(ERK1,2), induced by FGF7, led to growth without
      branching. Unlike TGFalpha, FGF7 promoted sustained proliferation as well as
      ectopic localization of, and increase in, keratin-6 expressing cells. The
      response of the explants to FGF10 was similar to that to FGF7. Simultaneous
      stimulation by FGF7 and TGFalpha indicated that the FGF7-induced MAPK(ERK1,2)
      signaling and associated phenotypes were dominant: FGF7 may prevent branching by
      suppression of two necessary TGFalpha-induced morphogenetic effectors, matrix
      metalloproteinase-3 (MMP-3/stromelysin-1), and fibronectin. Our findings indicate
      that expression of morphogenetic effectors, proliferation, and cell-type
      decisions during mammary organoid morphogenesis are intimately dependent on the
      duration of activation of MAPK(ERK1,2) activation.

PMID- 17448458
TI  - Fgf8 haploinsufficiency results in distinct craniofacial defects in adult
      zebrafish.
AB  - Significant progress has been made toward understanding the role of fgf8 in
      directing early embryonic patterning of the pharyngeal skeleton. Considerably
      less is known about the role this growth factor plays in the coordinated
      development, growth, and remodeling of the craniofacial skeleton beyond embryonic
      stages. To better understand the contributions of fgf8 in the formation of adult
      craniofacial architecture, we analyzed the skeletal anatomy of adult
      ace(ti282a)/fgf8 heterozygous zebrafish. Our results revealed distinct skeletal
      defects including facial asymmetries, aberrant craniofacial geometry, irregular
      patterns of cranial suturing, and ectopic bone formation. These defects are
      similar in presentation to several human craniofacial disorders (e.g.,
      craniosynostosis, hemifacial microsomia), and may be related to increased levels
      of bone metabolism observed in ace(ti282a)/fgf8 heterozygotes. Moreover, skeletal
      defects observed in ace(ti282a)/fgf8 heterozygotes are consistent with expression
      patterns of fgf8 in the mature craniofacial skeleton. These data reveal
      previously unrecognized roles for fgf8 during skeletogenesis, and provide a basis
      for future investigations into the mechanisms that regulate craniofacial
      development beyond the embryo.

PMID- 17448460
TI  - Histone methylation controls telomerase-independent telomere lengthening in cells
      undergoing dedifferentiation.
AB  - Cellular dedifferentiation underlies topical issues in biology such as
      regeneration and nuclear cloning and has common features in plants and animals.
      In plants, this process characterizes the transition of differentiated leaf cells
      to protoplasts (plant cells devoid of cell walls) and is accompanied by global
      chromatin reorganization associated with reprogramming of gene expression. A
      screen for mutants defective in proliferation and callus formation identified kyp
      2-a mutant in the KRYPTONITE (KYP)/SUVH4 gene encoding a histone H3 lysine 9
      (H3K9) methyltransferase. Analysis of telomere length revealed stochastic
      telomerase-independent lengthening of telomeres in wild type but not in kyp-2
      protoplasts. In kyp-2 mutant, telomeric repeats were no longer associated with
      dimethylated H3K9. The Arabidopsis telomerase reverse transcriptase (tert) mutant
      displayed accelerated proliferation despite its short telomeres, though it also
      showed accelerated cell death. Microarray analysis uncovered several components
      of the ubiquitin proteolytic system, which are downregulated in kyp-2 compared to
      wild-type protoplasts. Thus, our results suggest that histone methylation
      activity is required for the establishment/maintenance of the dedifferentiated
      state and/or reentry into the cell cycle, at least partly, through activation of
      genes whose products are involved in the ubiquitin proteolytic pathway. In
      addition, our results illuminate the complexity of cellular dedifferentiation,
      particularly the occurrence of DNA recombination that can lead to genome
      instability.

PMID- 17448459
TI  - Dynamics of embryonic pancreas development using real-time imaging.
AB  - Current knowledge about developmental processes in complex organisms has relied
      almost exclusively on analyses of fixed specimens. However, organ growth is
      highly dynamic, and visualization of such dynamic processes, e.g., real-time
      tracking of cell movement and tissue morphogenesis, is becoming increasingly
      important. Here, we use live imaging to investigate expansion of the embryonic
      pancreatic epithelium in mouse. Using time-lapse imaging of tissue explants in
      culture, fluorescently labeled pancreatic epithelium was found to undergo
      significant expansion accompanied by branching. Quantification of the real-time
      imaging data revealed lateral branching as the predominant mode of morphogenesis
      during epithelial expansion. Live imaging also allowed documentation of dynamic
      beta-cell formation and migration. During in vitro growth, appearance of newly
      formed beta-cells was visualized using pancreatic explants from MIP-GFP
      transgenic animals. Migration and clustering of beta-cells were recorded for the
      first time using live imaging. Total beta-cell mass and concordant aggregation
      increased during the time of imaging, demonstrating that cells were clustering to
      form "pre-islets". Finally, inhibition of Hedgehog signaling in explant cultures
      led to a dramatic increase in total beta-cell mass, demonstrating application of
      the system in investigating roles of critical embryonic signaling pathways in
      pancreas development including beta-cell expansion. Thus, pancreas growth in
      vitro can be documented by live imaging, allowing visualization of the developing
      pancreas in real-time.

PMID- 17448461
TI  - Transgenic analysis of Hoxd gene regulation during digit development.
AB  - In tetrapods, posterior Hoxd genes (from groups 10 to 13) are necessary to
      properly pattern the developing autopods, including the number and identities of
      digits. Their coordinated expression is achieved by sharing a global control
      region (GCR), which was isolated and localized 200 kb 5' (centromeric) of the
      gene cluster. However, in transgenic assays, the GCR was unable to fully
      recapitulate all aspects of the endogenous Hoxd expression patterns during distal
      limb development. In this paper, we further analyze the regulatory potential of
      this locus and report the characterization of Prox, a second enhancer element
      that contributes to the transcriptional activity of posterior Hoxd genes in
      developing distal limb buds. We show that the GCR and Prox elements complement
      each other and work in combination to correctly establish the late phase of Hoxd
      genes expression. Based on DNA sequence conservation and transgenic assays, we
      discuss the functions of these regulatory regions as well as a potential
      evolutionary scheme accounting for their emergence along with the evolution of
      tetrapod limbs.

PMID- 17448462
TI  - Ethanolamine and related amino alcohols increase basal and evoked release of [3H]
      D-aspartic acid from synaptosomes by enhancing the filling of synaptic vesicles.
AB  - This research examines the effects of ethanolamine and other amino alcohols on
      the dynamics of acridine orange (AO), oxonol V, and [3H]-D-aspartic acid in
      synaptic preparations isolated from mammalian brain. Ethanolamine concentration
      dependently enhanced AO release from synaptosomes. Similar effects were observed
      with methylethanolamine and dimethylethanolamine, but not choline. The
      enhancement of AO efflux by ethanolamine was independent of extrasynaptosomal
      calcium (in contrast to KCl-induced AO efflux), was unaffected by tetrodotoxin
      and did not involve depolarization of the synaptosomal plasma membrane. KCl was
      unable to release AO from synaptosomes following exposure to ethanolamine,
      however ethanolamine and other amino alcohols were found to enhance both basal
      and KCl-evoked release of [3H]-D-aspartic acid from synaptosomes. Using isolated
      synaptic vesicles we demonstrate that amino alcohols are able to 1) abolish the
      ATP-dependent intravesicular proton concentration (i.e. stimulate efflux of AO)
      in a similar way to carbonyl cyanide m-chlorophenylhydrazone (CCCP), 2) increase
      the ATP-supported transvesicular membrane potential (i.e. quench oxonol V
      fluorescence) in contrast to CCCP and 3) enhance intravesicular uptake of [3H]-D
      aspartic acid. These results suggest that positively charged, membrane impermeant
      amino alcohol species are generated within synaptic vesicles as they sequester
      protons. Cationic forms of these amino alcohols boost the transvesicular
      electrical potential which increases transmitter uptake into synaptic vesicles
      and facilitates enhancement of basal and evoked release of transmitter. Our data
      suggest a potential role for ethanolamine and related amino alcohols in the
      regulation of synaptic vesicle filling. These findings may also have relevance to
      neuropathophysiological states involving altered production of ethanolamine.

PMID- 17448463
TI  - Nuclear envelope precursor vesicle targeting to chromatin is stimulated by
      protein phosphatase 1 in Xenopus egg extracts.
AB  - The mechanism underlying targeting of the nuclear membrane to chromatin at the
      end of mitosis was studied using an in vitro cell-free system comprising Xenopus
      egg membrane and cytosol fractions, and sperm chromatin. The mitotic phase
      membrane, which was separated from a mitotic phase extract of Xenopus eggs and
      could not bind to chromatin, became able to bind to chromatin on pretreatment
      with a synthetic phase cytosol fraction of Xenopus eggs. When the cytosol
      fraction was depleted of protein phosphatase 1 (PP1) with anti-Xenopus PP1gamma1
      antibodies, this ability was lost. The addition of recombinant xPP1gamma1 to the
      PP1-depleted cytosol fraction restored the ability. These and other results
      suggested that dephosphorylation of mitotic phosphorylation sites on membranes by
      PP1 in the synthetic phase cytosol fraction promoted targeting of the membranes
      to chromatin. On the other hand, a fragment containing the chromatin-binding
      domain of lamin B receptor (LBR) but not emerin inhibited targeting of membrane
      vesicles. It was also shown that PP1 dephosphorylates a phosphate group(s)
      responsible for regulation of the binding of LBR to chromatin. A possible
      mechanism involving PP1 and LBR for the regulation of nuclear membrane targeting
      to chromatin was discussed.

PMID- 17448464
TI  - The arginine methyltransferase Rmt2 is enriched in the nucleus and co-purifies
      with the nuclear porins Nup49, Nup57 and Nup100.
AB  - Arginine methylation is a post-translational modification of proteins implicated
      in RNA processing, protein compartmentalization, signal transduction,
      transcriptional regulation and DNA repair. In a screen for proteins associated
      with the nuclear envelope in the yeast Saccharomyces cerevisiae, we have
      identified the arginine methyltransferase Rmt2, previously shown to methylate the
      ribosomal protein L12. By indirect immunofluorescence and subcellular
      fractionations we demonstrate here that Rmt2 has nuclear and cytoplasmic
      localizations. Biochemical analysis of a fraction enriched in nuclei reveals that
      nuclear Rmt2 is resistant to extractions with salt and detergent, indicating an
      association with structural components. This was supported by affinity
      purification experiments with TAP-tagged Rmt2. Rmt2 was found to co-purify with
      the nucleoporins Nup49, Nup57 and Nup100, revealing a novel link between arginine
      methyltransferases and the nuclear pore complex. In addition, a genome-wide
      transcription study of the rmt2Delta mutant shows significant downregulation of
      the transcription of MYO1, encoding the Type II myosin heavy chain required for
      cytokinesis and cell separation.

PMID- 17448465
TI  - Mouse model of diffuse brain damage following anoxia, evaluated by a new assay of
      generalized arousal.
AB  - Diffuse brain damage following anoxia due to cardiac failure, drowning, carbon
      monoxide exposure or other accidents constitutes a major medical problem. We have
      created a novel mouse model using the breathing of pure nitrogen, followed by a
      recently developed assay that reflects an operational definition of generalized
      arousal. The operational definition is precise, complete, and leads to
      quantitative, physical measures in a genetically tractable animal. Exposure to
      pure nitrogen for controlled periods had a surprising bifurcate effect: about
      half the mice survived with neurological measures that were virtually normal
      while the other half died. The new assay detected behavioral deficits unrevealed
      by neurological screening. Two important features of the results were that (i)
      deficits were not equal across the circadian cycle, and (ii) deficits were not
      equal across all the measures within the operational definition of arousal.
      Specific voluntary motor measurements were decreased in a manner that depended on
      the phase of the circadian cycle. Sensory responses were also decreased, with an
      emphasis on vertical movement responses; but, interestingly, fear learning was
      not damaged. This study establishes the first useful approach to diffuse brain
      damage in a genetically tractable animal. The model and its outcome measurements
      will be useful during future attempts at amelioration of acquired neurological
      disabilities following hypoxic-ischemic injuries.

PMID- 17448466
TI  - Analysis of betaB1-crystallin unfolding equilibrium by spin and fluorescence
      labeling: evidence of a dimeric intermediate.
AB  - A central step in understanding lens aging is to characterize the thermodynamic
      stability of its proteins and determine the consequences of changes in the
      primary sequence on their folding equilibria. For this purpose, destabilized
      mutations were introduced in betaB1-crystallin targeting the domain interface
      within the fold of a subunit. Global unfolding was monitored by tryptophan
      fluorescence while concomitant structural changes at the dimer interface were
      monitored by fluorescence and spin labels. Both spectral probes report explicit
      evidence of multi-state unfolding equilibrium. The biphasic nature of the
      unfolding curves was more pronounced at higher protein concentration. Distinct
      shifts in the midpoint of the second transition reflect the population of a
      dimeric intermediate. This intermediate may be a critical determinant for the
      life-long stability of the beta-crystallins and has important consequences on
      interactions with alpha-crystallin.

PMID- 17448467
TI  - Isolated teratozoospermia does not affect in vitro fertilization outcome and is
      not an indication for intracytoplasmic sperm injection.
AB  - OBJECTIVE: To reevaluate clinical management of isolated teratozoospermia, in
      couples initiating IVF. DESIGN: Retrospective analysis of fertility indices in
      535 cycles. SETTING: A large, university-based fertility center. PATIENT(S):
      Consecutive couples (n = 495) who had a semen analysis using Kruger/Tyberberg
      strict criteria at our center within 12 months before undergoing their first
      and/or second IVF cycle in 2002-2004 with >2 million postwash, motile sperm on
      the day of egg retrieval. INTERVENTION(S): Eggs were fertilized either by
      conventional IVF or ICSI. Semen analysis and gamete/embryo manipulation was
      standardized in all cases. MAIN OUTCOME MEASURE(S): Fertilization, fertilization
      failure, pregnancy, and live birth rates. RESULT(S): There was no statistical
      difference in fertilization, fertilization failure, pregnancy, and live birth
      rates in the first or second IVF cycle when comparing couples with isolated
      teratozoospermia (<5% normal morphology) to those with a normal semen analysis.
      Furthermore, no improvement in these outcomes was noted when ICSI was used to
      treat these teratozoospermic couples. CONCLUSION(S): Because isolated
      teratozoospermia generally does not impact on the major indices of IVF, these
      patients need not be subjected to the unnecessary cost and potential risks of
      ICSI. Future studies, however, should focus on different sperm morphologic and
      biochemical parameters to determine if they are important for clinical management
      in IVF.

PMID- 17448468
TI  - Use of the capillary-cumulus oophorus model for evaluating the selection of
      spermatozoa.
AB  - OBJECTIVE: To establish the action of the cumulus mass on the function of human
      spermatozoa. DESIGN: A prospective, controlled clinical study. SETTING: Academic
      infertility clinic. PATIENT(S): Semen donors and IVF patients. INTERVENTION(S):
      Donor human cumulus oophorus complex was aspirated into a glass Pasteur pipette.
      The semen of selected IVF patients was then loaded into the pipette, and the
      spermatozoa were allowed to transverse the cumulus matrix. The penetrated
      spermatozoa were then collected and underwent sperm functional tests, namely
      chlortetracycline, fluorescein isothiocyanate-labeled Pisum sativum, and
      chromomycin A(3). These were then compared with the fertilization rates of the
      IVF patients used in the study. MAIN OUTCOME MEASURE(S): The cumulus oophorus'
      action on capacitational processes of human spermatozoa. RESULT(S): The
      penetrated spermatozoa showed a higher tendency to be capacitated and acrosome
      reacted and to have superior chromosomal packaging quality, compared with the
      initial semen sample. CONCLUSION(S): Cumulus oophorus cells play a vital role in
      the fertilization process, especially during the capacitational stages. This
      method could physiologically select spermatozoa to be used in assisted
      reproductive techniques, especially intracytoplasmic sperm injection, in which
      sperm usually are immobile (because of low motility or because spermatozoa were
      testicularly retrieved).

PMID- 17448469
TI  - Age has no effect on de novo constitutional t(11;22) translocation frequency in
      sperm.
AB  - We analyzed de novo constitutional t(11;22) translocation frequency in sperm
      derived from normal healthy males as a function of the age of the sperm donors
      (from 25 to 51). Translocation-specific polymerase chain reaction demonstrated no
      age-dependent increment in the frequency of the rearrangements.

PMID- 17448470
TI  - Financial compensation of oocyte donors.

PMID- 17448471
TI  - Heterotopic abdominal pregnancy following two-blastocyst embryo transfer.
AB  - OBJECTIVE: To report a case of a heterotopic primary abdominal pregnancy after
      two-blastocyst IVF-ET. DESIGN: Case report. SETTING: University-based IVF
      program. PATIENT(S): A woman with a heterotopic abdominal pregnancy after IVF-ET.
      INTERVENTION(S): Pituitary down-regulation with luteal antagon, ovulation
      induction with menotropins, IVF-ET, progesterone in oil for luteal support,
      dilation and curettage for missed abortion, laparoscopy, and resection of
      abdominal gestation. MAIN OUTCOME MEASURE(S): Human chorionic gonadotropin
      levels, pelvic ultrasound examinations, and laparoscopic and pathologic findings.
      RESULT(S): A heterotopic abdominal pregnancy occurred after a two-blastocyst IVF
      ET. The concurrent intrauterine gestation resulted in a miscarriage.
      CONCLUSION(S): The number of embryos transferred has been identified as a
      powerful risk factor for heterotopic pregnancy; however, heterotopic pregnancy
      can occur following a two-embryo, blastocyst stage transfer.

PMID- 17448472
TI  - Establishment of autologous embryonic stem cells derived from preantral follicle
      culture and oocyte parthenogenesis.
AB  - OBJECTIVE: To evaluate whether autologous embryonic stem cells can be established
      without generating clone embryos. DESIGN: Prospective model study. SETTING:
      Gamete and stem cell biotechnology laboratory in Seoul National University,
      Seoul, Korea. ANIMAL(S): F1 hybrid B6D2F1 mice. INTERVENTION(S): Preantral
      follicles were cultured, and oocytes matured in the follicles were
      parthenogenetically activated. MAIN OUTCOME MEASURE(S): Preimplantation
      development and stem cell characterization. RESULT(S): More intrafollicular
      oocytes that were retrieved from secondary follicles matured and developed into
      blastocysts after parthenogenesis than those that were retrieved from primary
      follicles. Of those 35 blastocysts derived from 193 parthenotes, one line of
      colony-forming cells was established from the culturing of early secondary
      follicles. The established cells were positive for embryonic stem cell-specific
      markers and had normal diploid karyotype and telomerase activity. They
      differentiated into embryoid bodies in vitro and teratomas in vivo. Inducible
      differentiation of the established cells into neuronal lineage cells also was
      possible. CONCLUSION(S): Autologous embryonic stem cells can be established by
      preantral follicle culture and oocyte parthenogenesis. A combined technique of
      follicle culture and oocyte parthenogenesis that does not use developmentally
      competent oocytes has the potential to replace somatic cell nuclear transfer for
      autologous cell therapy.

PMID- 17448473
TI  - Effects of experimental increase of corticosterone levels on begging behavior,
      immunity and parental provisioning rate in house sparrows.
AB  - Begging is a complex display that is supposed to honestly indicate the need for
      food of nestlings, and, usually, parents use this information to adjust their
      investment in food provisioning. However, the mechanisms that ensure the honesty
      of begging as an indicator of need are still poorly known. It has been shown that
      levels of corticosterone (Cort), the hormone released during the stress response,
      raises during food shortage and is associated with increased begging rate.
      However, Cort also entails costs and these costs might prevent nestlings
      cheating. We tested this hypothesis in nestlings of the house sparrow. We
      experimentally increased levels of circulating Cort and investigated (1) the
      behavioral responses of nestlings, (2) the parental allocation of food and (3)
      the consequences on nestling growth and immune response. We found that Cort
      significantly increased begging rate but did not affect posture and position in
      the nest. Surprisingly, when begging effort was controlled statistically, control
      nestlings received more food from parents than Cort-treated nestlings. We also
      found that nestlings injected with Cort showed a weaker immune response and had
      lower body mass than controls. We suggest that Cort might have affected multiple
      aspects of nestling signaling, such as mouth color, and that parents use these
      multiple signals to adjust their feeding effort.

PMID- 17448474
TI  - Influence of reproductive season and rank on fecal glucocorticoid levels in free
      ranging male Verreaux's sifakas (Propithecus verreauxi).
AB  - Studies in anthropoid primates and other mammals suggest that reproductive
      season, rank, reproductive skew, aggression received, and social support are the
      major factors influencing glucocorticoid output. In which way these are also
      affecting adrenal function in lemurid primates has been studied rarely. Here, we
      examine the influence of reproductive season and rank on glucocorticoid output in
      male sifakas (Propithecus verreauxi), a species characterized by high breeding
      seasonality, a hierarchy among males and extreme reproductive skew towards
      dominant males. We established a fecal assay for non-invasively monitoring
      adrenal activity and collected 315 fecal samples during the reproductive and
      birth season from 10 male sifakas living in 5 groups in Western Madagascar. We
      found a significant effect of season on glucocorticoid output, with males
      exhibiting higher fecal glucocorticoid levels during the reproductive compared to
      the birth season in conjunction with an increase in overall aggression rates
      during the former period. Moreover, our data indicate a significant effect of
      rank on adrenocortical activity with dominant males exhibiting higher
      glucocorticoid levels than subordinate males in the reproductive season. However,
      dominant males did not differ significantly in rates of initiated or received
      aggression and rates of affiliative behavior from subordinates but showed
      significantly lower rates of submission. Given their highly formalized dominance
      relationships, we conclude that higher glucocorticoid output in dominant males
      during the 4-month reproductive season is likely related to higher energetic
      demands necessary to cope with the challenges of male reproduction rather than to
      physical demands of increased fighting frequency to maintain dominance status.
      High rank in sifakas may thus carry high costs, which, however, may be outweighed
      by monopolization of almost all paternities. In sum, our data generally support
      the findings on the relationship between environmental and social factors and
      glucocorticoid output found in non-lemurid primates.

PMID- 17448475
TI  - A low cost 3D shape measurement method based on a strip shifting pattern.
AB  - We present a simple, low cost but fast 3D shape measurement method. There is no
      limitation on the object's material and texture. We use a projector to project a
      strip shifting pattern on the object, and a digital camera to record videos of
      the scene. The distortion of the strip shadow on the object is used to get the
      object's 3D information. A novel space-time edge finding method is introduced to
      position the shadow edge accurately. This edge finding method overcomes the
      effect of inter-reflection and high light. Using this space-time information, we
      can calculate the pixels' 3D coordinates. To get the 3D shape of an object with
      black texture, we improve the black strip pattern to a 3-color strip pattern. The
      bad data are filtered by a post-processing 3D filter, which makes full use of the
      neighborhoods' geometric constraints and the view point constraint. Meanwhile,
      our measurement method is fast, regardless of the complexity of the shape.

PMID- 17448476
TI  - Expanding access to emergency contraception.
AB  - Emergency contraception (EC) is safe and has the potential to prevent unwanted
      pregnancies. However, use remains low in most settings, due to a range of
      barriers to access. This paper reviews key issues related to EC and describes
      recommendations reached during the Women's Health Alliance pre-Congress workshop,
      held in advance of the FIGO 2006 World Congress. The working group concluded that
      national societies of obstetrics and gynecology can play an important role in
      increasing access to this unique contraceptive method.

PMID- 17448477
TI  - Nursing and midwifery: Re-evaluating the relationship.

PMID- 17448478
TI  - On shear properties of trabecular bone under torsional loading: effects of bone
      marrow and strain rate.
AB  - To further improve our understanding of trabecular bone mechanical behavior in
      torsion, our objective was to determine the effects of strain rate, apparent
      density, and presence of bone marrow on trabecular bone shear material
      properties. Torsion tests of cylindrical trabecular bone specimens from sheep
      lumbar vertebrae with and without bone marrow were conducted. The bones with
      marrow were divided into two groups and tested at shear strain rates of 0.002 and
      0.05s(-1) measured at the specimen perimeter. The bones without marrow were
      divided into three groups and tested at shear strain rates of 0.002, 0.015, and
      0.05s(-1). Comparing the results of bones with and without marrow tested at low
      (0.002s(-1)) and high (0.05s(-1)) strain rates, presence of bone marrow did not
      have any significant effect on trabecular bone shear modulus and strength. In
      specimens without marrow, power relationships were used to define shear strength
      and modulus as dependent variables in terms of strain rate and apparent density
      as independent variables. The shear strength was proportional to the apparent
      density raised to the 1.02 power and to the strain rate raised to the 0.13 power.
      The shear modulus was proportional to the apparent density raised to the 1.08
      power and to the strain rate raised to the 0.07 power. This study provides
      further insight into the mechanism of bone failure in trauma as well as failure
      at the interface between bone and implants as it relates to prediction of
      trabecular bone shear properties.

PMID- 17448479
TI  - Dynamic and quasi-static compressive response of porcine muscle.
AB  - Research and application activities in impact biomechanics require dynamic
      response of biological tissues under high-rate loading. However, experimental
      difficulties have limited the characterization of soft tissues under such loading
      conditions. In this paper, we identify these technical challenges in dynamic
      compression experiments using a split Hopkinson pressure bar (SHPB) and present
      the remedies to overcome them. In order to subject the specimens to valid dynamic
      testing conditions, in addition to developing new pulse-shaping techniques and
      incorporating highly sensitive load-measuring transducers, annular thin-disc
      specimens radically different from regular solid specimens were used to minimize
      radial inertia effects that may overshadow the intrinsic material properties. By
      using this modified SHPB, the compressive stress-strain behavior of soft porcine
      muscle tissue was obtained along and perpendicular to the muscle fiber direction
      from quasi-static to dynamic strain rates. The results show that the non-linear
      compressive stress-strain responses in both directions are strongly strain-rate
      sensitive.

PMID- 17448480
TI  - Crushed bone grafts and a collagen membrane are not suitable for enhancing
      cartilage quality in the regeneration of osteochondral defects--an in vivo study
      in sheep.
AB  - Hyaline joint cartilage has only a limited potential for self-repair. Some of the
      published techniques for osteochondral defect therapy try to improve that
      potential. In this study, it was hypothesised that one of those surgical
      techniques, the crushed transplanted bone graft together with a collagen
      membrane, accelerates significantly the reconstruction of the subchondral bone
      plate and improves the mechanical and histological quality of repaired cartilage
      in osteochondral defects compared to an empty control defect. In order to test
      this hypothesis, defects were created in the left knee of 12 sheep and filled
      either with autologous crushed bone graft or left empty. The animals were
      sacrificed after 3 (n = 6) and 6 (n = 6) months. No differences were found either
      macroscopically or histomorphometrically between the bone graft and empty control
      defects. The biomechanical as well as the histological results of the bone graft
      defects were inferior to the control defects with inflammatory processes caused
      either by bone graft or membrane remnants. Based on the results in this sheep
      model, the filling of subchondral bone defects with compacted cancellous bone
      should be carefully reconsidered.

PMID- 17448481
TI  - New insights into long-bone biomechanics: are limb safety factors invariable
      across mammalian species?
AB  - The most common function of limb bones is to provide stiff levers acting against
      muscles and gravity; however, a general mechanical description is not yet
      available. This research attempts such a description by modeling the bone's
      intrinsic biomechanics through elastic stability of solid long cylinders
      considered in non-critical, transient and critical mechanical regimes
      distinguished conventionally through maximal resisting elastic strains. The non
      critical regime controls bones' adaptation through the safety factor (bone
      strength related to the peak functional stress) S2. This is ensured by bone
      diameter (d=1/3+beta) and bone-length (l=1/3-beta) scaling exponents generally
      following from compressive-stress constraints. Prange's index (0<beta<<1) known
      from long-bone allometry is related to the components of bone-stress tensor. The
      tensor-stress components depend weakly on body size, whereas the overall peak
      limb-compressive stress in running animals remains almost weight-independent. The
      transient regime (1<S<2) activated in animal vigorous activity determines elastic
      stability of slightly curved limb bones by avoiding critical-stress bending via
      non-critical torsion and critical torsion via moderate bending. A physical
      description of the transient regime suggests a united mechanical pattern.
      Established under most general consideration, the scaling rules for peak strains,
      forces, momenta, and stresses challenge locomotor patterns distinguished in small
      mammals and birds, lizards, primates and non-primate mammals. Taking into account
      that all scaling rules are limited by S=1 associated with critical regime,
      reliable estimates for critical body masses are obtained for living elephants and
      extinct dinosaurs. Our study of the variable limb safety factor provides evidence
      that land-dwelling and land-moving giants are biomechanically accommodated to the
      peak bending and torsion functional stresses, respectively.

PMID- 17448482
TI  - An unexpected observation concerning the effect of anionic additives on the
      retention behavior of basic drugs and peptides in reversed-phase liquid
      chromatography.
AB  - Anionic species with ion pair forming ability are commonly used to enhance the
      retention and efficiency of basic analytes in RPLC separations. However, little
      is known about the interactions between organic mobile phase modifiers and such
      ion pairing anions. In this work, we measured the magnitude of the retention
      increase of basic drugs and peptides upon addition of strong inorganic ion
      pairing anions (e.g. perchlorate) as a function of the volume fraction of
      modifier in acidic water-acetonitrile mobile phases on two different stationary
      phases. We found that the increase in retention upon addition of various salts
      depended strongly on the eluent strength. In general, larger retention increases
      upon addition of the anion were observed at higher organic fractions. Regression
      of retention against the volume fraction of organic modifier indicated that the
      ion pair forming anions substantially decreased S values while only slightly
      changing ln k'w values. The decrease in S is the major cause of the retention
      increase of basic drugs and peptides when such anions are added to the mobile
      phase.

PMID- 17448483
TI  - Effect of sample loop dimension on lysozyme refolding in size-exclusion
      chromatography.
AB  - The formation of misfolded protein aggregates, in particular inclusion bodies,
      has been widely considered as the major hindrance of good yield in refolding
      processes. To enhance the performance of protein refolding, extensive efforts
      were directed toward seeking out methods or means to reduce the aggregate
      production during the refolding process. Since simultaneous refolding and
      separation can be feasibly achieved within the packing matrices, size-exclusion
      chromatography (SEC) has been regarded as an efficient buffer exchange method to
      enhance protein refolding performance As of now, the effect of the process or
      operating parameters has yet to be thoroughly investigated. The present work is
      aimed at understanding how aggregate formation, as well as renaturation yield,
      varied with the diameter or length of sample loop in size-exclusion
      chromatography refolding process. Our results showed that not much difference was
      found in the patterns of aggregate formation for the contraction and the control
      cases. However, the formation of an additional peak was observed in the expansion
      cases. In addition, the amount of aggregates was not dependent on the sample loop
      diameter or length, but instead, influenced by injection volume and protein
      concentration. It was further concluded that a sample with large volume and low
      concentration was preferable for refolding process. We believe that the outcome
      from this work may shed light on the development of a more effective strategy for
      refolding processes.

PMID- 17448484
TI  - Prediction of retention time of cutinases tagged with hydrophobic peptides in
      hydrophobic interaction chromatography.
AB  - Hydrophobic interaction chromatography (HIC) is an important technique for
      protein purification, which exploits the separation of proteins based on
      hydrophobic interactions between the stationary phase ligands and hydrophobic
      regions on the protein surface. One way of enhancing the purification efficiency
      by HIC is the addition of short sequences of peptide tags to the target protein
      by genetic engineering, which could reduce the need for extra and expensive
      chromatographic steps. In the present work, a methodology for predicting
      retention times of cutinases tagged with hydrophobic peptides in HIC is
      presented. Cutinase from Fusarium solani pisi fused to tryptophan-proline (WP)
      tags, namely (WP)2 and (WP)4, and produced in Saccharomyces cerevisiae strains,
      were used as model proteins. From the simulations, the methodology based on
      tagged hydrophobic definition proposed by Simeonidis et al. (Phitagged),
      associated to a quadratic model for predicting dimensionless retention times,
      showed small differences (RMSE<0.022) between observed and estimated retention
      times. The difference between observed and calculated retention times being lower
      than 2.0% (RMSE<0.022) for the two tagged cutinases at three different stationary
      phases, except for the case of cut_(wp)2 in octyl sepharose-2 M ammonium
      sulphate. Therefore, we consider that the proposed strategy, based on tagged
      surface hydrophobicity, allows prediction of acceptable retention times of
      cutinases tagged with hydrophobic peptides in HIC.

PMID- 17448485
TI  - Barrier film protected, and mixed solvent optimized micro-scale membrane
      extraction of methyl carbamate pesticides.
AB  - Hollow fiber based microextraction has emerged as an effective alternative to
      conventional preconcentration techniques. The loss of the extractant solvent
      through the membrane has been an important issue, and dip-coating with a barrier
      film is a method for stabilizing the acceptor. Typically, only one solvent is
      used to serve as the extractant, which limits the range of compounds that can be
      analyzed simultaneously. Mixing solvents in varying proportions can increase the
      range of compounds enriched. This paper reports the optimization of the
      microextraction system by implementing a barrier film to reduce solvent loss, in
      conjunction with the use of mixed solvents to enrich a broader spectrum of
      analytes. A group of five carbamate pesticides were studied here. The detection
      limits were at ppb levels and the enrichment was as high as 1600 times depending
      upon the solvent. R2 and %RSD ranged from 0.9501 to 0.9991 and 1.90 and 9.53,
      respectively.

PMID- 17448486
TI  - Covalently closed microemulsions in presence of triblock terpolymers.
AB  - This paper is focused on the influence of polystyrene (PS)-poly(1,4-butadiene)
      (PB)-poly(ethylene oxide) (PEO) triblock terpolymers on the w/o microemulsion of
      the pseudo-ternary system water/sodium dodecylsulfate (SDS)/xylene-pentanol.
      Despite the insolubility of the copolymer in water as well as in the xylene
      pentanol mixture, it can be incorporated into the w/o microemulsion and
      interactions between the triblock terpolymer molecules and the anionic surfactant
      headgroups can be detected by differential scanning calorimetry (DSC)
      measurements. Furthermore, dynamic light scattering measurements were used to
      determine the aggregate diameter of the modified microemulsions. For lower
      polymer concentrations large aggregates between 100 and 500 nm can be observed.
      Surprisingly, at a higher terpolymer concentration of 5 wt%, significant smaller
      aggregate diameters can be identified by dynamic light scattering and Cryo-SEM.
      One can conclude that the copolymers are incorporated in the inverse
      microemulsion droplets, where the PB blocks cover the water droplets. The
      thermally induced radical cross-linking of the butadiene units in the presence of
      azobisisobutyronitrile (AIBN) leads then to covalently closed nanocapsules with
      an average size of 10 nm.

PMID- 17448487
TI  - Functionalized polymer colloids bearing primary amino groups.
AB  - Polymer colloids are prepared via radicalic emulsion polymerisation of
      butylacrylate. Functionalization with amino groups is achieved by
      copolymerisation of 2-amino-ethylmethacrylates. In order to over-compensate the
      positive surface charges resulting from the amino groups additionally
      vinylbenzenesulfonic acid is copolymerized. The size of the resulting particles
      is controlled by the molar ratio of amino to sulfonic acid groups. The
      suitability of amino groups for coupling reactions is demonstrated by
      electrophilic addition of fluorescein-5-isothiocyanate. The resulting particles
      are characterized by dynamic light scattering and zeta potential measurements as
      well as by optical spectroscopy. The suitability of labelled particles for
      optical tracer experiments is demonstrated by fluorescence correlation
      spectroscopy.

PMID- 17448488
TI  - Thickening properties and emulsification mechanisms of new derivatives of
      polysaccharide in aqueous solution 2. The effect of the substitution ratio of
      hydrophobic/hydrophilic moieties.
AB  - The thickening properties and association behavior of aqueous solutions of HHM
      HEC (hydrophobically-hydrophilically modified hydroxyethyl cellulose) with
      various hydrophobic and hydrophilic substitution degrees were investigated. The
      HHM-HEC was used as an oil-in-water emulsifier and stable compositional regions
      were investigated as a function of polymer concentration and substitution degree.
      The viscosity of aqueous solutions of HHM-HEC increased drastically at lower
      concentration for HHM-HEC with a higher hydrophobic/hydrophilic substitution
      ratio. The intensity ratio of the first and third vibrational bands of pyrene
      (I(1)/I(3)) decreased with the increase of HHM-HEC concentration and the
      I(1)/I(3) reached a lower plateau at a lower concentration for HHM-HEC with a
      higher hydrophobic/hydrophilic substitution ratio. The concentration ranges of
      HHM-HEC solutions which stabilize O/W emulsions differ by the
      hydrophobic/hydrophilic substitution ratio. However the viscosity ranges of these
      HHM-HEC solutions were almost the same regardless of the hydrophobic/hydrophilic
      substitution ratio. At the suitable concentration range for emulsification, HHM
      HEC networks have two properties: (1) oil particle retention capacity and (2)
      laxation which can trap emulsified particles.

PMID- 17448489
TI  - Surface arsenic speciation of a drinking-water treatment residual using X-ray
      absorption spectroscopy.
AB  - Drinking-water treatment residuals (WTRs) present a low-cost geosorbent for As
      contaminated waters and soils. Previous work has demonstrated the high affinity
      of WTRs for As, but data pertaining to the stability of sorbed As is missing.
      Sorption/desorption and X-ray absorption spectroscopy (XAS), both XANES (X-ray
      absorption near edge structure) and EXAFS (extended X-ray absorption fine
      structure) studies, were combined to determine the stability of As sorbed by an
      Fe-based WTR. Arsenic(V) and As(III) sorption kinetics were biphasic in nature,
      sorbing >90% of the initial added As (15,000 mg kg(-1)) after 48 h of reaction.
      Subsequent desorption experiments with a high P load (7500 mg kg(-1)) showed
      negligible As desorption for both As species, approximately <3.5% of sorbed As;
      the small amount of desorbed As was attributed to the abundance of sorption
      sites. XANES data showed that sorption kinetics for either As(III) or As(V)
      initially added to solution had no effect on the sorbed As oxidation state. EXAFS
      spectroscopy suggested that As added either as As(III) or as As(V) formed inner
      sphere mononuclear, bidentate complexes, suggesting the stability of the sorbed
      As, which was further corroborated by the minimum As desorption from the Fe-WTR.

PMID- 17448490
TI  - Synthesis and size control of monodisperse copper nanoparticles by polyol method.
AB  - We describe herein the synthesis of metallic copper nanoparticles in the presence
      of poly(vinylpyrrolidone), employed as a protecting agent, via a polyol method in
      ambient atmosphere. The obtained copper particles were confirmed by XRD to be
      crystalline copper with a face-centered cubic (fcc) structure. We observed
      monodisperse spherical copper nanoparticles with a diameter range 45+/-8 nm. The
      particle size and its distribution are controlled by varying the synthesis
      parameters such as the reducing agent concentration, reaction temperature, and
      precursor injection rate. The precursor injection rate plays an important role in
      controlling the size of the copper nanoparticles. On the basis of XPS and HRTEM
      results, we demonstrate that the surface of the copper is surrounded by amorphous
      CuO and that poly(vinylpyrrolidone) is chemisorbed on the copper surface.

PMID- 17448491
TI  - Adsorption kinetics of phosphate and arsenate on goethite. A comparative study.
AB  - The adsorption kinetics of phosphate and arsenate on goethite is studied and
      compared. Batch adsorption experiments were performed at different adsorbate
      concentrations, pH, temperatures and stirring rates. For both oxoanions the
      adsorption rate increases by increasing adsorbate concentration, decreasing pH
      and increasing temperature. It does not change by changing stirring rate. The
      adsorption takes place in two processes: a fast one that takes place in less than
      5 min and a slow one that takes place in several hours or more. The rate of the
      slow process does not depend directly on the concentration of phosphate or
      arsenate in solution, but depends linearly on the amount of phosphate or arsenate
      that was adsorbed during the fast process. Apparent activation energies and
      absence of stirring rate effects suggest that the slow process is controlled by
      diffusion into pores, although the evidence is not conclusive. The similarities
      in the adsorption kinetics of phosphate and arsenate are quantitatively shown by
      using a three-parameters equation that takes into account both the fast and the
      slow processes. These similarities are in line with the similar reactivity that
      phosphate and arsenate have in general and may be important for theoretical and
      experimental studies of the fate of these oxoanions in the environment.

PMID- 17448492
TI  - Interfacial behavior of common food contact polymer additives.
AB  - Irganox 1076 (IN1076) and Irganox 1010 (IN1010), phenol containing species often
      used as antioxidant additives in food packaging polymers have both hydrophilic
      and hydrophobic functional groups. Consequently these additives are likely to
      absorb to surfaces where their free energy is minimized. Experiments described in
      this work examine the two-dimensional phase behavior and vibrational structure of
      IN1076 and IN1010 films adsorbed to the air/water interface. Surface pressure
      isotherms show that repeated compression of these films leads to continued
      irreversible loss of molecules and that on a per molecule basis, this loss is
      more pronounced for IN1076 than for IN1010. Differences in the surface properties
      of these two antioxidant additives are interpreted based on differences in
      molecular structure. Surface specific vibrational measurements of these organic
      films show very little conformational order, implying that even when closely
      packed, both antioxidant species have little affinity for forming highly
      organized domains. These findings have important ramifications for mechanisms
      that reduce antioxidant activity in polymers as well as descriptions of
      antioxidant blooming on polymer surfaces.

PMID- 17448493
TI  - Detachment of liquid droplets from fibres--experimental and theoretical
      evaluation of detachment force due to interfacial tension effects.
AB  - The detachment of barrel-shaped oil droplets from metal, glass and polymer fibres
      was examined using an atomic force microscope (AFM). The AFM was used to detach
      the droplets from the fibres while measuring the force-distance relationship. A
      novel fibre-droplet interfacial tension model was applied to predict the force
      required to draw the droplet away from its preferential axisymmetric position on
      the fibre, and also to predict the maximal force required to detach the droplet.
      The model assumes that the droplet retains a spherical shape during detachment,
      i.e., that droplet distortion is negligible. This assumption was found to be
      reasonably accurate for small radius oil droplets (<10 microm), however less
      accurate for larger droplets (>25 microm). However, it was found that the model
      produced a good agreement with the maximal detachment force measured
      experimentally--regardless of droplet size and degree of deformation--even though
      the model could not predict droplet extension beyond a length of one droplet
      radius.

PMID- 17448494
TI  - Molecular mechanisms underlying sex pheromone production in the silkmoth, Bombyx
      mori: characterization of the molecular components involved in bombykol
      biosynthesis.
AB  - Many species of female moths produce sex pheromones to attract conspecific males.
      To date, sex pheromones from more than 570 moth species have been chemically
      identified. Most moth species utilize Type I pheromones that consist of straight
      chain compounds 10-18 carbons in length with a functional group of a primary
      alcohol, aldehyde, or acetate ester and usually with several double bonds. In
      contrast, some moth species use unsaturated hydrocarbons or hydrocarbon epoxides,
      classified as Type II lepidopteran pheromones, as sex pheromones. Studies over
      the past three decades have demonstrated that female moths usually produce sex
      pheromones as multi-component blends where the ratio of the individual components
      is precisely controlled, thus making it possible to generate species-specific
      pheromone blends. As for the biosynthesis of Type I pheromones, it is well
      established that they are de novo synthesized in the pheromone gland (PG) through
      modifications of fatty acid biosynthetic pathways. However, as many of the
      molecular components within the PG cells (i.e., enzymes, proteins, and small
      regulatory molecules) have not been functionally characterized, the molecular
      mechanisms underlying sex pheromone production in PG cells remain poorly
      understood. To address this, we have recently characterized some of the molecules
      involved in the biosynthesis of the sex pheromone bombykol in the silkmoth,
      Bombyx mori. Characterization of these, and other, key molecules will facilitate
      our understanding of the precise mechanisms underlying lepidopteran sex pheromone
      production.

PMID- 17448495
TI  - Evidence for dynamic interplay of different oligomeric states of UDP-N
      acetylglucosamine 2-epimerase/N-acetylmannosamine kinase by biophysical methods.
AB  - The bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine
      kinase (GNE) is a key enzyme for the biosynthesis of sialic acids, the terminal
      sugars of glycoconjugates associated with a variety of physiological and
      pathological processes such as cell adhesion, development, inflammation and
      cancer. In this study, we characterized rat GNE by different biophysical methods,
      analytical ultracentrifugation, dynamic light-scattering and size-exclusion
      chromatography, all revealing the native hydrodynamic behavior and molar mass of
      the protein. We show that GNE is able to reversibly self-associate into different
      oligomeric states including monomers, dimers and tetramers. Additionally, it
      forms non-specific aggregates of high molecular mass, which cannot be
      unequivocally assigned a distinct size. Our results also indicate that ligands of
      the epimerase domain of the bifunctional enzyme, namely UDP-N-acetylglucosamine
      and CMP-N-acetylneuraminic acid, stabilize the protein against aggregation and
      are capable of modulating the quaternary structure of the protein. The presence
      of UDP-N-acetylglucosamine strongly favors the tetrameric state, which therefore
      likely represents the active state of the enzyme in cells.

PMID- 17448496
TI  - Dictyostelium discoideum salvages purine deoxyribonucleosides by highly specific
      bacterial-like deoxyribonucleoside kinases.
AB  - The salvage of deoxyribonucleosides in the social amoeba Dictyostelium
      discoideum, which has an extremely A+T-rich genome, was investigated. All native
      deoxyribonucleosides were phosphorylated by D. discoideum cell extracts and we
      subcloned three deoxyribonucleoside kinase (dNK) encoding genes. D. discoideum
      thymidine kinase was similar to the human thymidine kinase 1 and was specific for
      thymidine with a K(m) of 5.1 microM. The other two cloned kinases were
      phylogenetically closer to bacterial deoxyribonucleoside kinases than to the
      eukaryotic enzymes. D. discoideum deoxyadenosine kinase (DddAK) had a K(m) for
      deoxyadenosine of 22.7 microM and a k(cat) of 3.7 s(-1) and could not efficiently
      phosphorylate any other native deoxyribonucleoside. D. discoideum deoxyguanosine
      kinase was also a purine-specific kinase and phosphorylated significantly only
      deoxyguanosine, with a K(m) of 1.4 microM and a k(cat) of 3 s(-1). The two purine
      specific deoxyribonucleoside kinases could represent ancient enzymes present in
      the common ancestor of bacteria and eukaryotes but remaining only in a few
      eukaryote lineages. The narrow substrate specificity of the D. discoideum dNKs
      reflects the biased genome composition and we attempted to explain the strict
      preference of DddAK for deoxyadenosine by modeling the active center with
      different substrates. Apart from its native substrate, deoxyadenosine, DddAK
      efficiently phosphorylated fludarabine. Hence, DddAK could be used in the
      enzymatic production of fludarabine monophosphate, a drug used in the treatment
      of chronic lymphocytic leukemia.

PMID- 17448497
TI  - Pathological alterations of the climbing fibres of the cerebellum in vascular
      dementia: a Golgi and electron microscope study.
AB  - The climbing fibres originating from the inferior olivary nucleus act as a
      powerful excitation on the Purkinje cells of the cerebellar cortex that may play
      a substantial role in the motor performances and the learning of new motor
      skills. In vascular dementia the existent vascular alterations may induce many
      hypoxic or ischemic phenomena, among the others, in the olivocerebellar system
      affecting the climbing fibres in their way to the molecular layer of the
      cerebellar cortex. In autopsy cases of vascular dementia, the application of
      silver impregnation technique and electron microscopy revealed a substantial
      decrease of the number of the climbing fibres in the cortex of the vermis, the
      flocculus and the cerebellar hemispheres. The presynaptic varicosities and the
      synaptic terminals of the climbing fibres on the Purkinje cell dendrites were
      decreased in number and moreover were characterized by a marked poverty of
      synaptic vesicles. The synaptic cleft was mostly abnormal and wider than 20 nm.
      Mitochondrial abnormalities, such as elongated mitochondria with disruption of
      the cristae were seen in the terminal branches of the climbing fibre arborization
      as well as in the presynaptic components. The blood capillaries demonstrated a
      considerable thickness of the basal membrane and perivascular astrocytic
      proliferation, whereas the tight junctions between the endothelial cells were
      ultrastructurally intact. We would hypothesize that the morphological and
      morphometric alterations of the climbing fibres of the cerebellar cortex in cases
      of vascular dementia might be associated with the frequently noticed difficulty
      in the performance of fine and skilful movements by the patients.

PMID- 17448498
TI  - Symmetries by base substitutions in the genetic code predict 2(') or 3(')
      aminoacylation of tRNAs.

PMID- 17448499
TI  - A theoretical study on the evolution of male parental care and female multiple
      mating: effects of female mate choice and male care bias.
AB  - Male parental care and female multiple mating are seen in many species in spite
      of the cost they entail. Moreover, they even coexist in some species though
      polyandry, by reducing paternity confidence of caregiving males, seems to hinder
      the evolution of paternal care. Previous studies have investigated the
      coevolutionary process of paternal care and polyandry under various simplifying
      assumptions, including random mating and random provision of male care. We extend
      these models to examine possible effects of female mate choice and male care
      bias, assuming that (a) monandrous females mate preferentially with caregiving
      males while polyandrous females compromise their preference in order to mate with
      multiple males and (b) caregiving males tend to direct their care to offspring of
      monandrous females. Our models suggest that both the female preference and the
      male bias always favor caregiving males while they may not always facilitate the
      evolution of monandry.

PMID- 17448500
TI  - Ecological character displacement caused by reproductive interference.
AB  - We carried out a theoretical investigation of whether ecological character
      displacement can be caused by reproductive interference. Our model assumes that a
      quantitative character is associated with both resource use and species
      recognition, and that heterospecific mating incurs costs. The model shows that
      ecological character displacement can occur as a consequence of evolution of
      premating isolation; this conclusion is based on the premise that resource
      competition is less intense between species than within species and that the
      ecological character also contributes to premating isolation. When resource
      competition between species is intense, extinction of either species may occur by
      competitive exclusion before ecological character divergence. Some observational
      studies have shown that character displacement in body size is associated with
      not only resources use but also species recognition. We propose that body size
      displacement can occur as a consequence of evolution of premating isolation. Our
      results suggest that ecological character displacement results from reproductive
      character displacement.

PMID- 17448501
TI  - A complex mathematical model of the human menstrual cycle.
AB  - Despite the fact that more than 100 million women worldwide use birth control
      pills and that half of the world's population is concerned, the menstrual cycle
      has so far received comparatively little attention in the field of mathematical
      modeling. The term menstrual cycle comprises the processes of the control system
      in the female body that, under healthy circumstances, lead to ovulation at
      regular intervals, thus making reproduction possible. If this is not the case or
      ovulation is not desired, the question arises how this control system can be
      influenced, for example, by hormonal treatments. In order to be able to cover a
      vast range of external manipulations, the mathematical model must comprise the
      main components where the processes belonging to the menstrual cycle occur, as
      well as their interrelations. A system of differential equations serves as the
      mathematical model, describing the dynamics of hormones, enzymes, receptors, and
      follicular phases. Since the processes take place in different parts of the body
      and influence each other with a certain delay, passing over to delay differential
      equations is deemed a reasonable step. The pulsatile release of the gonadotropin
      releasing hormone (GnRH) is controlled by a complex neural network. We choose to
      model the pulse time points of this GnRH pulse generator by a stochastic process.
      Focus in this paper is on the model development. This rather elaborate
      mathematical model is the basis for a detailed analysis and could be helpful for
      possible drug design.

PMID- 17448502
TI  - A general multi-trait-based framework for studying the effects of biodiversity on
      ecosystem functioning.
AB  - Environmental change is as multifaceted as are the species and communities that
      respond to these changes. Current theoretical approaches to modeling ecosystem
      response to environmental change often deal only with single environmental
      drivers or single species traits, simple ecological interactions, and/or steady
      states, leading to concern about how accurately these approaches will capture
      future responses to environmental change in real biological systems. To begin
      addressing this issue, we generalize a previous trait-based framework to
      incorporate aspects of frequency dependence, functional complementarity, and the
      dynamics of systems composed of species that are defined by multiple traits that
      are tied to multiple environmental drivers. The framework is particularly well
      suited for analyzing the role of temporal environmental fluctuations in
      maintaining trait variability and the resultant effects on community response to
      environmental change. Using this framework, we construct simple models to
      investigate two ecological problems. First, we show how complementary resource
      use can significantly enhance the nutrient uptake of plant communities through
      two different mechanisms related to increased productivity (over-yielding) and
      larger trait variability. Over-yielding is a hallmark of complementarity and
      increases the total biomass of the community and, thus, the total rate at which
      nutrients are consumed. Trait variability also increases due to the lower levels
      of competition associated with complementarity, thus speeding up the rate at
      which more efficient species emerge as conditions change. Second, we study
      systems in which multiple environmental drivers act on species defined by
      multiple, correlated traits. We show that correlations in these systems can
      increase trait variability within the community and again lead to faster
      responses to environmental change. The methodological advances provided here will
      apply to almost any function that relates species traits and environmental
      drivers to growth, and should prove useful for studying the effects of climate
      change on the dynamics of biota.

PMID- 17448504
TI  - Long-term biological effects of petroleum residues on fiddler crabs in salt
      marshes.
AB  - In September 1969, the Florida barge spilled 700,000L of No. 2 fuel oil into the
      salt marsh sediments of Wild Harbor (Buzzards Bay, MA). Today the aboveground
      environment appears unaffected, but a substantial amount of moderately degraded
      petroleum still remains 8-20cm below the surface. The salt marsh fiddler crabs,
      Uca pugnax, burrow into the sediments at depths of 5-25cm, and are chronically
      exposed to the spilled oil. Behavioral studies conducted with U. pugnax from Wild
      Harbor and a control site, Great Sippewissett marsh, found that crabs exposed to
      the oil avoided burrowing into oiled layers, suffered delayed escape responses,
      lowered feeding rates, and achieved lower densities. The oil residues are
      therefore biologically active and affect U. pugnax populations. Our results add
      new knowledge about long-term consequences of spilled oil, a dimension that
      should be included when assessing oil-impacted areas and developing management
      plans designed to restore, rehabilitate, or replace impacted areas.

PMID- 17448503
TI  - Involvement of nPKC-MAPK pathway in the decrease of nucleophosmin/B23 during
      megakaryocytic differentiation of human myelogenous leukemia K562 cells.
AB  - Human myelogenous leukemia K562 cells were induced to undergo megakaryocytic
      differentiation by long-term treatment with phorbol ester 12-O-tetradecanoyl
      phorbol-13-acetate (TPA). The protein level of nucleophosmin/B23 (NPM/B23), a
      nucleolar protein, was substantially decreased upon TPA treatment. In this study,
      we found that the proteasome inhibitors blocked the decrease of NPM/B23 protein
      in response to TPA, suggesting the proteasomes were involved in the
      downregulation of NPM/B23 upon megakaryocytic differentiation. To investigate the
      signaling pathway in the downregulation of NPM/B23 during early TPA-induced
      megakaryocytic differentiation of K562 cells, K562 cells were treated with TPA in
      the presence of the PKC isozyme-selective inhibitors, GF109203X and Go 6976, or
      MEK1 inhibitor, PD98059. The decrease of NPM/B23 protein in the TPA-treated K562
      cells was blocked by GF109203X but not by Go 6976, suggesting the involvement of
      novel PKCs in the downregulation of NPM/B23 during TPA-induced megakaryocytic
      differentiation of K562 cells. The application of MEK1 inhibitor PD98059 upon TPA
      treatment blocked the TPA-induced decrease of NPM/B23 protein and aborted the
      megakaryocytic differentiation but not to break through the cell growth arrest.
      Unlike NPM/B23, the degradation of nucleolin in the TPA-treated K562 cells could
      not be blocked by PD98059 while the TPA-induced megakaryocytic differentiation
      was abrogated. The decrease of NPM/B23 protein seems to be more correlated with
      the novel PKC-MAPK-induced megakaryocytic differentiation than another nucleolar
      protein, nucleolin. Taken together, our results indicated that novel PKC-MAPK
      pathway was required for the decrease of NPM/B23 during TPA-induced
      megakaryocytic differentiation.

PMID- 17448505
TI  - Convergence rate estimation for the TKF91 model of biological sequence length
      evolution.
AB  - The TKF91 model of biological sequence evolution describes changes in the
      sequence length via an infinite state-space birth-death process, which we term
      the TKF91-BD process. The TKF91 model assumes that, for any pair of modern
      sequences, the ancestral sequence has equilibrium length distribution, an
      assumption whose validity has not been rigorously investigated. We obtain
      explicit upper and lower bounds on the rate of convergence to equilibrium for the
      distribution of the TKF91-BD process. We show that the rate of convergence of the
      TKF91-BD process for protein sequences with parameter values inferred from
      sequence data on alpha and beta globins is too low to guarantee convergence to
      equilibrium on a reasonable timescale. For the analyzed nucleotide sequences, the
      convergence is faster, but the equilibrium sequence length is unrealistically
      small. The Jukes-Cantor model of nucleotide substitutions can converge
      considerably faster than the length evolution model for both amino acid and
      nucleotide sequences, while the speed of convergence for the Kimura model is
      close to that for the TKF91-BD process describing nucleotide sequences.

PMID- 17448506
TI  - Micronuclei, genetic polymorphisms and cardiovascular disease mortality in a
      nested case-control study in Italy.
AB  - AIM: To validate the predictive value of micronuclei (MN) in peripheral blood
      lymphocytes (PBL) and glutathione-S-transferases (GSTs) polymorphisms (GSTM1 and
      GSTT1) for mortality risk (MR) of cardiovascular diseases (CVD). METHODS: Blood
      samples from 1650 healthy subjects selected from the general population were
      collected between June 1991 and November 1993, and slides were immediately
      prepared for MN assessment. The vital status, or the cause of death, was
      monitored for all subjects until January 2005. At the end of the follow-up, 111
      deaths were recorded and 39 CVD cases were observed (age range=42-88 years). Two
      thousand binucleated (BN) cells/subject were scored for the MN assay and GSTs
      genotypes were assessed on the DNA extracted from the blood or serum samples.
      RESULTS: A significantly higher MN frequency was recorded for the case group in
      comparison with the control group (n=67, Kruskall-Wallis test, p=0.006) and GSTT1
      null genotype was significantly less frequent in CVD patients (chi(2)-test,
      p=0.036). The influence of other factors were evaluated using a unconditional
      logistic regression that confirmed a significant association of GSTT1 positive
      genotype with an increased OR for CVD (OR=6.29, 95% CI 1.32-29.95) beside a
      significant effect of age (OR=1.13, 95% CI 1.03-1.26 year(-1)). Finally, subjects
      with an higher MN frequency showed a higher MR for CVD (Log-rank test, p=0.001).
      CONCLUSIONS: MN confirmed to be a suitable cytogenetic biomarker for early
      prediction of CVD death. The GSTT1 positive genotype is associated with an
      increased MR for CVD.

PMID- 17448507
TI  - Cerebral compensation during motor imagery in Parkinson's disease.
AB  - In neurodegenerative disorders, neural damage can trigger compensatory mechanisms
      that minimize behavioural impairments. Here, we aimed at characterizing cerebral
      compensation during motor imagery in Parkinson's disease (PD), while controlling
      for altered motor execution and sensory feedback. We used a within-patient design
      to compare the most and least affected hand in 19 right-handed PD patients with
      markedly right-lateralized symptoms. We used a motor imagery (MI) task in which
      the patients were required to judge the laterality of hand images, rotated either
      in a lateral or in a medial orientation with respect to the body sagittal plane.
      This design allowed us to compare cerebral activity (using fMRI) evoked by MI of
      each hand separately, while objectively monitoring task performance. Reaction
      times and parieto-premotor activity increased in a similar manner as a function
      of stimulus rotation during motor imagery of left and right hands. However,
      patients were markedly slower when judging images of the affected hand in lateral
      orientations, and there was a corresponding increase in activity in the right
      extrastriate body area (EBA) and occipito-parietal cortex during mental rotation
      of the affected hand. Furthermore, these regions increased their connectivity
      towards the left PMd for right (affected) hands in a lateral orientation. We
      infer that, in strongly lateralized PD patients, motor imagery of the most
      affected hand exploits additional resources in extrastriate visual areas. These
      findings characterize the cerebral bases of the increased dependence on visual
      information processing during the generation of motor plans in PD, pointing to
      its compensatory role.

PMID- 17448508
TI  - Fluctuating asymmetry as an animal welfare indicator -- a review of methodology
      and validity.
AB  - It has been suggested that fluctuating asymmetry (FA) reflects an animal's
      ability to cope with the sum of challenges during its growing period and, thus,
      is a potential welfare indicator. In this review we investigate the evidence of
      associations between FA and other welfare indicators measured at the level of the
      individual and of effects of welfare-relevant environmental conditions on FA in
      populations of captive birds and mammals including humans. As the question of
      validity cannot be treated independently from the quality of the available data,
      first a checklist for the proper measurement and analysis of FA is drafted and
      used to evaluate the methodological quality of the various studies. We recommend
      this checklist to be used as a standard for future FA studies. We found 17
      relevant studies on associations between FA and other welfare indicators, and 36
      studies on effects of welfare-relevant factors on FA. Frequent methodological
      shortcomings or insufficient methodological information allow for only cautious
      conclusions. The proportion of significant results supporting the link between
      higher FA and poorer welfare is only moderately high. Independent from
      statistical significance, almost all studies found the relationship between FA
      and welfare to be prevailingly in the expected direction. FA is a promising
      measure of animal welfare, despite a great number of open questions, e.g.
      relating to the ontogeny of FA or its sensitivity to various stressors. The
      considerable potential of FA as a welfare indicator makes it worthwhile to pursue
      more intensely validation studies as well as applied studies. These studies
      should pay particular attention to an appropriate methodological approach.

PMID- 17448510
TI  - [Neurosensory disorders and functional impairment after bilateral sagittal split
      osteotomy: role of the anatomical situation of the alveolar pedicle in 76
      patients].
AB  - INTRODUCTION: Bilateral sagittal split osteotomy (BSSO) of the mandibular ramus
      is the most frequent orthognatic surgery. The risk of neurosensory disorders
      remains high even their incidence varies according to numerous publications. The
      anatomical location of the alveolar pedicle seems to be one of the most important
      factors in these disorders. The aim of this study was to determine its exact
      role. MATERIAL AND METHOD: We performed a retrospective study on 76 patients and
      152 osteotomy sides, all of them operated according to the Epker technique by the
      same surgeon between 2000 and 2004. For each operative side we noted the position
      of the inferior alveolar nerve during the split: Type I entirely in the internal
      cortical bone, Type II partially in the external cortical bone, Type III mostly
      or completely in the external cortical bone. The neurosensory disorders were
      recorded during clinical examination and simply classified into two categories:
      "absent" or "present". The outcome was noted during the postoperative follow-up
      at D1; D15; M1,5, M6, and M12. After that, it was documented through a written
      questionnaire or telephone conversation. RESULTS: Since there was no difference
      between the right and the left sides, the study enclosed all of the operative
      sides together (152). The anatomical distribution was: 97 Type I (63.8%), 28 Type
      II (18.4%), and 27 Type III (17.8%). Immediate postoperative neurosensory
      disorders (D1) occurred on 74.3% of sides, with important significant differences
      between Type I (64.9%) on one hand, Type II (89.2%) and Type III (92.6%) on the
      other hand. At one year of follow-up, the rate of neurosensory disorders was
      20.4% with also a difference between Type I (13.4%) and Types II and III (35.7%
      and 29.6%). DISCUSSION: The anatomical location of the alveolar pedicle seems to
      be important. This study confirms previously published studies and raises the
      question of CT scan assessment before performing BSSO.

PMID- 17448511
TI  - A Markov chain Monte Carlo strategy for sampling from the joint posterior
      distribution of pedigrees and population parameters under a Fisher-Wright model
      with partial selfing.
AB  - A simple population genetic model is presented for a hermaphrodite annual
      species, allowing both selfing and outcrossing. Those male gametes (pollen)
      responsible for outcrossing are assumed to disperse much further than seeds.
      Under this model, the pedigree of a sample from a single locality is loop-free. A
      novel Markov chain Monte Carlo strategy is presented for sampling from the joint
      posterior distribution of the pedigree of such a sample and the parameters of the
      population genetic model (including the selfing rate) given the genotypes of the
      sampled individuals at unlinked marker loci. The computational costs of this
      Markov chain Monte Carlo strategy scale well with the number of individuals in
      the sample, and the number of marker loci, but increase exponentially with the
      age (time since colonisation from the source population) of the local population.
      Consequently, this strategy is particularly suited to situations where the sample
      has been collected from a population which is the result of a recent colonisation
      process.

PMID- 17448512
TI  - Residential exposure to drinking water arsenic in Inner Mongolia, China.
AB  - In the Ba Men region of Inner Mongolia, China, a high prevalence of chronic
      arsenism has been reported in earlier studies. A survey of the arsenic
      contamination among wells from groundwater was conducted to better understand the
      occurrence of arsenic (As) in drinking water. A total of 14,866 wells (30% of all
      wells in the region) were analyzed for their arsenic-content. Methods used to
      detect arsenic were Spectrophotometric methods with DCC-Ag (detection limit, 0.5
      microg of As/L); Spot method (detection limit, 10 microg of As/L); and air
      assisted Colorimetry method (detection limit, 20 microg of As/L). Arsenic
      concentrations ranged from below limit of detection to 1200 microg of As/L.
      Elevated concentrations were related to well depth (10 to 29 m), the date the
      well was built (peaks from 1980-1990), and geographic location (near mountain
      range). Over 25,900 individuals utilized wells with drinking water arsenic
      concentrations above 20 microg of As/L (14,500 above 50 microg of As/L-the
      current China national standard in drinking water and 2198 above 300 microg of
      As/L). The presented database of arsenic in wells of the Ba Men region provides a
      useful tool for planning future water explorations when combined with geological
      information as well as support for designing upcoming epidemiological studies on
      the effects of arsenic in drinking water for this region.

PMID- 17448513
TI  - Effect of dietary calcium propionate on performance, enzyme activities and
      aflatoxin residues in broilers fed a diet containing low levels of aflatoxin B1.

PMID- 17448516
TI  - Effects of transient temperature conditions on the divergence of activated sludge
      bacterial community structure and function.
AB  - The effect of temperature fluctuations on bacterial community structure and
      function in lab-scale sequencing batch reactors treating bleached kraft mill
      effluent was investigated. An increase in temperature from 30 to 45 degrees C
      caused shifts in both bacterial community structure and function. Triplicate
      reactors were highly similar for 40 days following startup. After the temperature
      shift, their community structure and function started to diverge from each other
      and from the control. A multi-response permutation procedure confirmed that the
      variability in community structure between transient and control reactors were
      greater than that among the triplicate transient reactors. The fact that these
      disturbances manifest themselves in different ways in apparently identical
      reactors suggests a high degree of variability between replicate systems.

PMID- 17448514
TI  - Transcriptional profile of Rous Sarcoma Virus transformed chicken embryo
      fibroblasts reveals new signaling targets of viral-src.
AB  - Transformation of chicken fibroblasts in vitro by Rous Sarcoma Virus represents a
      model of cancer in which a single oncogene, viral src, uniformly and rapidly
      transforms primary cells in culture. We experimentally surveyed the
      transcriptional program affected by Rous Sarcoma Virus (RSV) in primary culture
      of chicken embryo fibroblasts. As a control, we used cells infected with non
      transforming RSV mutant td106, in which the src gene was deleted. Using
      Affymetrix GeneChip Chicken Genome Arrays, we report 811 genes that were
      modulated more than 2.5 fold in the virus transformed cells. Among these, 409
      genes were induced and 402 genes were repressed by viral src. From the repertoire
      of modulated genes, we selected 20 genes that were robustly changed. We then
      validated and quantified the transcriptional changes of most of the 20 selected
      genes by real-time PCR. The set of strongly induced genes contains vasoactive
      intestinal polypeptide, MAP kinase phosphatase 2 and follistatin, among others.
      The set of strongly repressed genes contains TGF beta 3, TGF beta-induced gene,
      and deiodinase. The function of several robustly modulated genes sheds new light
      on the molecular mechanism of oncogenic transformation.

PMID- 17448517
TI  - River sediments provide a link between catchment pressures and ecological status
      in a mixed land use Scottish River system.
AB  - This study evaluates water quality, suspended and bed sediment, ecological and
      catchment land use data for 13 catchments of the mixed land use River Dee, NE
      Scotland, where pollution point sources are limited. Samples were collected at
      key times of biological activity (early and late summers). Mean river water
      concentrations were smaller in main stem and upland sites and greater in
      tributaries where agricultural pressures were greater and were 2-41 microgPO(4)
      Pl(-1), 8-58 microg total dissolved Pl(-1) and 1-6 mg l(-1) of suspended
      particulate matter (SPM). SPM was 7-372 times enriched in biologically available
      P (BAP; determined using an FeO paper strip method) and 2-122 times in organic C
      relative to bed sediments. Ratios in river water concentrations of BAP attributed
      to the SPM (0.1-1.0 microgPl(-1)) to PO(4)-P had the greatest range at baseflow
      (0.01-0.80) with larger values for low land use intensity catchments. During May
      chlorophyll a concentrations were related to SPM BAP (p<0.001), but later in
      summer to PO(4)-P, and there was a corresponding change in the organic
      composition of SPM observed by IR spectroscopy. SPM concentrations and SPM BAP
      were better related to intensive grassland land use (p<0.001) than was PO(4)-P
      concentration (p<0.01) and also predicted abundances of filter feeding
      macroinvertebrates (p<0.001). Within this river system SPM quantity and
      composition proved to be an indicator of river biogeochemical functioning and
      requires further investigation as a potentially sensitive monitoring tool and to
      increase our understanding of chemical ecological links.

PMID- 17448518
TI  - The influence of oxidation reduction potential and water treatment processes on
      quartz lamp sleeve fouling in ultraviolet disinfection reactors.
AB  - Ultraviolet (UV) disinfection systems are incorporated into drinking water
      production facilities because of their broad-spectrum antimicrobial capabilities,
      and the minimal disinfection by-product formation that generally accompanies
      their use. Selection of an optimal location for a UV system within a drinking
      water treatment facility depends on many factors; a potentially important
      consideration is the effect of system location on operation and maintenance
      issues, including the potential for fouling of quartz surfaces. To examine the
      effect of system location on fouling, experiments were conducted at a groundwater
      treatment facility, wherein aeration, chlorination, and sand filtration were
      applied sequentially for treatment. In this facility, access to the water stream
      was available prior to and following each of the treatment steps. Therefore, it
      was possible to examine the effects of each of these unit operations on fouling
      dynamics within a UV system. Results indicated zero-order formation kinetics for
      the fouling reactions at all locations. Increases in oxidation reduction
      potential, caused by water treatment steps such as aeration and chlorination,
      increased the rate of sleeve fouling and the rate of irradiance loss within the
      reactor. Analysis of metals in the sleeve foulant showed that calcium and iron
      predominate, and relative comparisons of foulant composition to water chemistry
      highlighted a high affinity for incorporation into the foulant matrix for both
      iron and manganese, particularly after oxidizing treatment steps. Fouling
      behavior was observed to be in qualitative agreement with representations of the
      degree of saturation, relative to the metal:ligand combinations that are believed
      to comprise a large fraction of the foulants that accumulate on the surfaces of
      quartz jackets in UV systems used to treat water.

PMID- 17448519
TI  - Chromate transport through columns packed with surfactant-modified zeolite/zero
      valent iron pellets.
AB  - Chromate transport through columns packed with zeolite/zero valent iron (Z/ZVI)
      pellets, either untreated or treated with the cationic surfactant
      hexadecyltrimethylammonium (HDTMA), was studied at different flow rates. In the
      presence of sorbed HDTMA, the chromate retardation factor increased by a factor
      of five and the pseudo first-order rate constant for chromate reduction increased
      by 1.5-5 times. The increase in rate constant from the column studies was
      comparable to a six-fold increase in the rate constant determined in a batch
      study. At a fast flow rate, the apparent delay in chromate breakthrough from the
      HDTMA modified Z/ZVI columns was primarily caused by the increase in chromate
      reduction rate constant. In contrast, at a slower flow rate, the retardation in
      chromate transport from the HDTMA modified Z/ZVI columns mainly originated from
      chromate sorption onto the HDTMA modified Z/ZVI pellets. Due to dual porosity,
      the presence of immobile water was responsible for the earlier breakthrough of
      chromate in columns packed with zeolite and Z/ZVI pellets. The results from this
      study further confirm the role of HDTMA in enhancing sorption and reduction
      efficiency of contaminants in groundwater remediation.

PMID- 17448520
TI  - Comment on "Effects of organic ligands on fractionation of rare earth elements
      (REEs) in hydroponic plants: an application to the determination of binding
      capacities by humic acid for modelling" by Ding et al. [Chemosphere 65 (2006)
      1942-1948].

PMID- 17448521
TI  - Comments and decision of the editor Prof. Dr. Michael Oehme from the
      environmental chemistry section of Chemosphere.

PMID- 17448522
TI  - Duckweed (Lemna gibba) growth inhibition bioassay for evaluating the toxicity of
      olive mill wastes before and during composting.
AB  - Two-phase olive mill waste (TPOMW) is considered the main problem confronting the
      modern oil extraction and processing industry. Composting has been recently
      proposed as a suitable method to treat TPOMW so that it is suitable for use in
      agriculture. In the work reported here, the Lemna gibba bioassay was tested to
      assess the toxicity of TPOMW before and during the composting process. The method
      was compared with the Lepidium sativum bioassay and with other chemical maturity
      indices traditionally reported in the literature. The L. gibba test proved to be
      a simple, sensitive, and accurate method to evaluate toxicity before and during
      the composting of TPOMW. Plant growth response was measured by two methods:
      counting the number of fronds (leaves) and measuring total frond area (TFA) with
      image analysis software. Compared to the counting of fronds (L. gibba) or seeds
      (L. sativum), the use of area-measuring software permitted a very rapid, unbiased
      and easy way of analysing the toxicity of TPOMW before and during composting.
      Although the accuracy of the frond count method was similar to the traditional
      cress seed test, data analysis showed that the TFA measurement method was
      statistically more accurate (significantly lower variance) than the frond count
      approach. Highly significant correlations were found between TFA and some
      important maturation indices commonly reported in literature indicating that the
      L. gibba bioassay can be a useful tool to determine the degree of maturity of
      TPOMW composts.

PMID- 17448523
TI  - Determination of selenium by GFAAS in slurries of fish feces to estimate the
      bioavailability of this micronutrient in feed used in pisciculture.
AB  - This paper presents a simple, fast and sensitive method to determine selenium in
      samples of feces and of fish feed by graphite furnace atomic absorption
      spectrometry (GFAAS) through the direct introduction of slurries of the samples
      into the spectrometer's graphite tube. The limits of detection (LOD) and
      quantification (LOQ) calculated for 20 readings of the blank of the standard
      slurries (0.50% m/v of feces or feed devoid of selenium) were 0.31 microg l(-1)
      and 1.03 microg l(-1), respectively, for the standard feces slurries and 0.35
      microg l(-1) and 1.16 microg l(-1), respectively, for the standard feed slurries.
      The proposed method was applied in studies of bioavailability of selenium in
      different fish feeds and the results proved consistent with that obtained from
      samples mineralized by acid digestion using the microwave oven.

PMID- 17448524
TI  - Sources and temporal dynamics of arsenic in a New Jersey watershed, USA.
AB  - We examined potential sources and the temporal dynamics of arsenic (As) in the
      slightly alkaline waters of the Wallkill River, northwestern New Jersey, where
      violations of water-quality standards have occurred. The study design included
      synoptic sampling of stream water and bed sediments in tributaries and the
      mainstem, hyporheic-zone/ground water on the mainstem, and seasonal and diurnal
      sampling of water at selected mainstem sites. The river valley is bordered by
      gneiss and granite highlands and shale lowlands and underlain by glacial deposits
      over faulted dolomites and the Franklin Marble. Ore bodies in the Marble, which
      have been mined for rare Zn ore minerals, also contain As minerals. Tributaries,
      which drain predominantly forested and agricultural land, contributed relatively
      little As to the river. The highest concentrations of As (up to 34 mug/L)
      emanated from the outlet of man-made Lake Mohawk at the river's headwaters; these
      inputs varied substantially with season--high during warm months, low during cold
      months, apparently because of biological activity in the lake. Dissolved As
      concentrations were lower (3.3 microg/L) in river water than those in ground
      water discharging into the riverbed (22 microg/L) near the now-closed Franklin
      Mine. High total As concentrations (100-190 mg/kg) on the <0.63 microm fraction
      of bed sediments near the mine apparently result from sorption of the As in the
      ground-water discharge as well as from the As minerals in the streambed. As
      concentrations in river water were diluted during high stream flow in fall,
      winter and spring, and concentrated during low flow in summer. In unfiltered
      samples from a wetlands site, diurnal cycles in trace-element concentrations
      occurred; As concentrations appeared to peak during late afternoon as pH
      increased, but Fe, Mn, and Zn concentrations peaked shortly after midnight. The
      temporal variability of As and its presence at elevated concentrations in ground
      water and sediments as well as streamwater demonstrate the importance of (1)
      sampling a variety of media and (2) determining the time scales of As variability
      to fully characterize its passage through a river system.

PMID- 17448525
TI  - On the issue of limiting nutrient and predictions of cyanobacteria in aquatic
      systems.
AB  - This study aims at bridging the gap between freshwater and marine eutrophication
      studies by presenting (1) a cross-system analysis of the relationship between
      chlorophyll and the total nitrogen (TN) to total phosphorus (TP) ratio (2) a
      general model to predict concentrations of cyanobacteria from data on TP, the
      TN/TP ratio, salinity and temperature, and (3) a general trophic level
      classification for aquatic systems based on chlorophyll classes (for oligo-, meso
      , eu- and hypertrophic systems). The data compiled in this study concerns more
      than 500 lakes and coastal areas covering a very wide domain in terms of nutrient
      concentrations and salinity. There was no simple relationship between the TN/TP
      ratio and empirical chlorophyll concentrations or concentrations of
      cyanobacteria. Variations in TP rather than TN generally seem to be more
      important to predict variations among systems in chlorophyll-a and cyanobacteria.
      Different "bioavailable" forms of the nutrients (DIN, DIP, phosphate, nitrate,
      etc.) have been shown to have very high coefficients of variation (CV), which
      means that many samples are needed to obtain reliable empirical data which are
      necessary in models aiming for high predictive power and practical usefulness.

PMID- 17448526
TI  - Immunolocalisation of members of the polypeptide N-acetylgalactosaminyl
      transferase (ppGalNAc-T) family is consistent with biologically relevant altered
      cell surface glycosylation in breast cancer.
AB  - An extensive family of UDP-N-alpha-d-galactosamine: polypeptide N
      acetylgalactosaminyltransferases (polypeptide N-acetylgalactosaminyltransferases,
      ppGalNAc-T's) catalyse the attachment of the first N-acetylgalactosamine (GalNAc)
      monosaccharide to the polypeptide at the initiation of O-linked glycosylation of
      proteins. Some members of the family are broadly expressed while others are more
      restricted in their distribution, their expression and activity being confined to
      certain cells or tissues, being associated with physiological states or
      differentiation. Their careful regulation, which is not well understood, may
      mediate the synthesis of varied glycoforms of cellular proteins with different
      biological activities. Disruptions in glycosylation are a common feature of
      cancer and may have functional significance. Immunocytochemistry with confocal
      scanning laser microscopy was employed to detect members of the ppGalNAc-T
      family, ppGalNAc-T1, -T2, -T3, -T4 and -T6 in a range of breast cell lines. The
      cells were chosen to represent a range of phenotypes from 'normal'/benign (HMT
      3,522), primary, non-metastatic breast cancer (BT 474), to aggressive, metastatic
      breast cancer (ZR75-1, T47D, MCF-7, DU 4,475). They stably synthesise varying
      levels, consistent with origin and phenotype, of aberrantly glycosylated
      glycoproteins featuring exposed, terminal GalNAc residues, including the cancer
      associated Tn antigen, which, in numerous studies, have been associated with
      metastatic competence and poor cancer prognosis. GalNAc-T1 and -T2 were
      detectable at low levels in all cell lines studied. ppGalNAc-T4, which has never
      been described in breast, was very weakly detectable in BT 474, MCF7 and T47D.
      ppGalNAc-T3 and -T6 were weakly detectable or undetectable, respectively, in the
      cell line HMT 3,522 derived from 'normal'/benign breast epithelium, but were
      readily detectable in all malignant cell lines. Thus, a broader range of ppGalNAc
      T's were detectable in the malignant cell lines in comparison to the
      'normal'/benign cells, where only the 'housekeeping' ppGalNAc-T1 and -T2 were
      present. Expression of normally tightly restricted ppGalNAc-T's may result in
      initiation of O-linked glycosylation at normally unoccupied potential
      glycosylation sites leading to altered glycoforms of proteins with changed
      biological activity which may contribute to the pathogenesis of cancer.

PMID- 17448527
TI  - Self-organization in and on biological spheres.
AB  - Three biological settings involving self-organization performed by the Turing
      Child field inside a sphere and on its surface are considered. In the first
      setting the interior of a sphere made up of cells communicating via gap junctions
      is considered. It is suggested that the Turing-Child self-organization is the
      cause of radial polarization, the first differentiation of an early mammalian
      embryo. In the second setting, the Turing example of gastrulation of a hollow
      cellular sphere is considered. It is shown that Child's experimental patterns are
      predicted and explained by the Turing-Child theory. The third setting is the
      interior of a biological cell, and it is suggested that it is the self
      organization of the Turing-Child field that causes the formation of the mitotic
      spindle.

PMID- 17448528
TI  - Protective effects of Nicotiflorin on reducing memory dysfunction, energy
      metabolism failure and oxidative stress in multi-infarct dementia model rats.
AB  - The present study aimed to determine whether Nicotiflorin, a natural flavonoid
      extracted from coronal of Carthamus tinctorius, has a protective effect on
      cerebral multi-infarct dementia in rats. The multi-infarct dementia model rats
      were prepared by injecting man-made micro-thrombi into the right hemisphere. The
      administration groups were treated once daily with 30, 60 and 120 mg/kg
      Nicotiflorin (i.g.) from 5 days before ischemia operation to 3 days after the
      operation for biochemical examination, 10 days for Morris water maze study and
      morphological observations and 20 days for eight-arm radial maze task. 2,3,5
      triphenyltetrazolium chloride (TTC) staining showed that infarct volume of each
      Nicotiflorin administration group was much smaller than that of vehicle-treated
      multi-infarct dementia group, and hematoxylin and eosin (HE) staining showed that
      histopathological abnormalities of each Nicotiflorin group were also much lighter
      than that of vehicle-treated multi-infarct dementia group. Each Nicotiflorin
      group showed much better spatial memory performance in Morris water maze tests
      and eight-arm radial maze task compared with the vehicle-treated multi-infarct
      dementia group, significantly attenuated the elevation of lactic acid and
      malondialdehyde (MDA) contents and the decrease in lactate dehydrogenase (LDH),
      Na(+)K(+)ATPase, Ca(2+)Mg(2+)ATPase and superoxide dismutase (SOD) activity in
      the brain tissue which was composed of striatum, cortex and hippocampus of the
      ischemia hemisphere at day 3 after ischemia operation. These results suggest that
      Nicotiflorin has protective effects on reducing memory dysfunction, energy
      metabolism failure and oxidative stress in multi-infarct dementia model rats.

PMID- 17448529
TI  - Evaluation of lung maturity by amniotic fluid analysis in equine neonate.
AB  - The aim of this study was to gather useful new data for evaluation of lung
      maturity in the neonatal foal. Because equine neonatal intensive therapy is very
      expensive, a precocious diagnosis could help to express a prognosis and to offer
      a respiratory support early after birth, increasing the survival rate and
      reducing complications. Amniotic fluid was collected at parturition on n=18
      mares. Lamellar bodies were isolated in the amniotic fluid and measured with
      transmission electron microscopy (TEM). Furthermore two tests on amniotic fluid
      that are commonly used in humane medicine were utilized: lecithin/sphingomyelin
      ratio (L/S) and lamellar body count (LBC). L/S ratio was determined using thin
      layer chromatography (TLC) and, for the first time in equine amniotic fluid, with
      high performance liquid chromatography (HPLC). LBC was performed with an
      automated blood cell counter. The mean of the L/S ratio obtained in mature foals
      was 2.5 with TLC and 2.7 with HPLC. The mean LBC in the same group was
      48x10(3)/microL. The Spearman's Rank correlation test found a significant
      correlation between TLC and Apgar score (R=0.66, p<0.01), between TLC and cord pH
      (R=0.65, p<0.05), between HPLC and Apgar score (R=0.63, p<0.01) and between cord
      pH and Apgar score (R=0.82, p<0.01). The Student's t-test did not found a
      significant difference between L/S ratio performed with TLC and with HPLC. These
      methods may be useful for evaluation of lung maturity in the equine species, but
      further studies on a large number of mature and premature foals are necessary to
      establish equine pulmonary maturity standards.

PMID- 17448530
TI  - Cryo-scanning electron microscopy (Cryo-SEM) of boar semen frozen in medium
      straws and MiniFlatPacks.
AB  - In this study we demonstrate, in the frozen state, the architecture of frozen
      boar spermatozoa collected from the sperm-rich fraction of ejaculates (n=13) from
      four fertile boars packed and split-frozen in medium-straws (MS) and
      MiniFlatPacks (MFP), cross-sectioned in the frozen state and evaluated by image
      analysis on images obtained by use of cryo-scanning electron microscopy (Cryo
      SEM). The tested hypothesis was that the degree of in situ dehydration and levels
      of homogeneity of boar semen either frozen in MSs or MFPs packages differ between
      them, with MFPs allowing for a more uniform dehydration of the spermatozoa and a
      higher cryosurvival, monitored by computer assisted sperm analysis (CASA) as
      proportion of linearly motile spermatozoa, compared to semen packaged and
      processed in MSs. The organization and relative surface of biological material
      (veins; e.g., frozen extender, bound water, solutes and spermatozoa) as well as
      free water (lakes) was measured as the degree of dehydration of the samples. The
      apparent organization of lakes and veins differed between packages, with the MFPs
      depicting larger lakes than the MSs. The sizes of the lakes in the latter
      appeared, moreover, highly asymmetrical depending on their position of the
      section. The relative surface of these lakes per section, respectively veins
      differed between packages (P<0.05), indicating a larger amount of free-water
      (lakes; 81.73+/-2.07% vs. 77.91+/-1.57%) in the MFPs and, consequently, thinner
      veins than in MSs. In conclusion, MFPs seem to allow for a more homogenous
      dehydration of the spermatozoa/frozen extender compared to MSs, which might
      account for their somewhat better sperm quality post-thaw.

PMID- 17448531
TI  - Effect of adhesion to cavity walls on the mechanical properties of resin
      composites.
AB  - OBJECTIVES: To evaluate the regional mechanical properties of resin composite
      under free and constrained conditions during polymerization. METHODS: Forty
      cavities (8mm diameter and 5mm depth) were fabricated in resin blocks. Half of
      the cavities were bonded and the other half left un-bonded. The cavities were
      bulk-filled with one of the following composites: flowable composite (Palfique
      Estelite LV, Unifil Lo Flo), and Universal composites (Clearfil AP-X, Palfique
      Estelite Sigma), followed by photo-curing for 30s. After 24h storage, each
      specimen was sliced parallel to the long axis to harvest three slabs. The middle
      slab was serially sliced to harvest five sticks, which were trimmed to an hour
      glass shape for measurement of regional ultimate tensile strength (UTS). The
      remaining semi-circular slabs were polished for microhardness measurement (KHN).
      Data were analyzed using three-way ANOVA followed by Tukey's HSD test and t-test
      (alpha=.05). RESULTS: The KHNs of all the resin composites were not significantly
      different between the bonded and unbonded groups at each cavity depth (p>0.05).
      The Ucapital TE, CyrillicS of the bonded group of flowable composites was
      significantly lower than those of the un-bonded group at the upper regions
      (p<0.05), while for universal composites, there were no significant differences
      in UTS between the bonded and un-bonded groups (p>0.05), although Clearfil AP-X
      had a trend toward lower UTS under the constrained condition at the upper
      regions. SIGNIFICANCE: The UTS of resin composite decreases due to polymerization
      shrinkage stress when polymerized under a constrained condition, however, these
      effects were dependent upon regions in the cavity and the resin materials.

PMID- 17448532
TI  - Hypoxia in the East China Sea: one of the largest coastal low-oxygen areas in the
      world.
AB  - Anoxia and hypoxia have been widely observed in estuarine and coastal regions
      over the past few decades; however, few reports have focused on the East China
      Sea (ECS). In June and August 2003, two cruises sampled at stations covering
      almost the entire shelf of the ECS to examine hypoxic events and their potential
      causes. In August, DO concentrations <2-3 mg l(-1) covered an area estimated at
      greater than 12,000 km(2) (or 432 km(3) volume). In contrast, water column DO
      concentrations exceeded 4 mg l(-1) throughout most of the shelf region. A sharp
      density gradient was observed under the mixed layer in August, restricting
      vertical re-aeration across this strong pycnocline. Oxygen depletion events, such
      as that described here for the ECS shelf, are fueled by decomposition of newly
      produced marine and river-borne biogenic substances (as well as older residual
      organic matter) deposited to the bottom waters.

PMID- 17448534
TI  - The GCB subtype of diffuse large B-cell lymphoma is less frequent in Asian
      countries.
AB  - Patients with the germinal center B-cell-like (GCB) subtype of diffuse large B
      cell lymphoma (DLBCL) have a significantly better survival rate than those with
      non-GCB DLBCL. Several studies have examined the proportions of GCB and non-GCB
      subtypes in large series of DLBCL patients, but it remains unclear if these
      proportions are the same in different countries. We performed an
      immunohistochemical analysis of the numbers of GCB and non-GCB subtypes in a
      large number of patients with DLBCL in Japan and compared the results with
      literature data for other countries. We found that 71 of 248 patients (29%) had
      the GCB phenotype and 177 patients (71%) had the non-GCB subtype of DLBCL among
      our patient population. Assessment of data collected from other studies showed
      that 31% of DLBCL patients (102/330) have the GCB subtype in Asian countries, but
      50% (206/416) express GCB phenotypes in Western countries; based on these data,
      the occurrence of the GCB subtype of DLBCL was significantly less in Asian
      countries (p<0.001). Since patients with the GCB phenotype of DLBCL have better
      survival, future studies of DLBCL should recognize the difference in the
      proportions of GCB and non-GCB subtypes of DLBCL between Asian and Western
      populations.

PMID- 17448533
TI  - Biomolecular surface coating to enhance orthopaedic tissue healing and
      integration.
AB  - Implant osseointegration is a prerequisite for clinical success in orthopaedic
      and dental applications, many of which are restricted by loosening. Biomaterial
      surface modification approaches, including calcium-phosphate ceramic coatings and
      macro/microporosity, have had limited success in promoting integration. To
      improve osseointegration, titanium surfaces were coated with the glycine
      phenylalanine-hydroxyproline-glycine-glutamate-arginine (GFOGER) collagen-mimetic
      peptide, selectively promoting alpha2beta1 integrin binding, a crucial event for
      osteoblastic differentiation. Titanium surfaces presenting GFOGER triggered
      osteoblastic differentiation and mineral deposition in bone marrow stromal cells,
      leading to enhanced osteoblastic function compared to unmodified titanium.
      Furthermore, this integrin-targeted coating significantly improved in vivo peri
      implant bone regeneration and osseointegration, as characterized by bone-implant
      contact and mechanical fixation, compared to untreated titanium in a rat cortical
      bone-implant model. GFOGER-modified implants also significantly enhanced
      osseointegration compared to surfaces modified with full-length type I collagen,
      highlighting the importance of presenting specific biofunctional domains within
      the native ligand. In addition, this biomimetic implant coating is generated
      using a simple, single-step procedure that readily translates to a clinical
      environment with minimal processing and cytotoxicity concerns. Therefore, this
      study establishes a biologically active and clinically relevant implant-coating
      strategy that enhances bone repair and orthopaedic implant integration.

PMID- 17448535
TI  - Neuroglian on hemocyte surfaces is involved in homophilic and heterophilic
      interactions of the innate immune system of Manduca sexta.
AB  - Neuroglian, a member of the L1 family of cell adhesion molecules (L1-CAMs), is
      expressed on surfaces of granular cells and a subset of large plasmatocytes of
      Manduca sexta that act as foci for hemocyte aggregation during the innate immune
      response. Neuroglian expressed on surfaces of transfected Sf9 cells induced their
      homophilic aggregation, with the aggregation being abolished in the presence of
      recombinant immunoglobulin (Ig) domains of neuroglian. Neuroglian and its Ig
      domains also can interact with hemocyte-specific integrin (HS integrin) as
      demonstrated with an enzyme-linked immunoassay and a surface plasmon resonance
      (SPR) assay. Neuroglian double-stranded (ds) RNA not only depresses expression of
      neuroglian in hemocytes but also depresses the cell-mediated encapsulation
      response of these hemocytes to foreign surfaces. After injection of a monoclonal
      antibody (MAb 3B11) into M. sexta larvae that recognizes the Ig domains of
      neuroglian, the cell-mediated encapsulation response of hemocytes was likewise
      inhibited. The Ig domains of neuroglian are involved in both homophilic and
      heterophilic interactions, and subsets of these six different Ig domains may
      affect different functions of neuroglian.

PMID- 17448536
TI  - 3T magnetic resonance arteriography in pediatric cerebrovascular disease.
AB  - Based on a series of 20 cases, eight with 1.5T and 3T MRA's, 3T MRA provides
      improvement over 1.5T MRA in imaging the vessels of the circle of Willis in
      pediatric patients with vascular disease. Dephasing artifact is reduced and
      laminal stenosis or occlusions become better depicted.

PMID- 17448537
TI  - Human neutrophil peptide-1 inhibits both the classical and the lectin pathway of
      complement activation.
AB  - Human neutrophil peptide-1 (HNP-1) is a member of the alpha-defensin family.
      Defensins are cationic antimicrobial peptides, which play an important role in
      the antimicrobial response to microorganisms. In addition, recent studies have
      revealed the involvement of defensins in inflammation, immunity and wound repair.
      Defensins are present in the azurophilic granules of neutrophils and are released
      upon neutrophil stimulation. Previous studies showed that HNP-1 binds to C1q and
      inhibits the classical complement pathway. In view of the structural and
      functional similarity between C1q and MBL, we have now examined the interactions
      between HNP-1 and MBL. We observed a dose-dependent binding of HNP-1 to MBL in
      calcium-free buffer, indicating that HNP-1 binds to MBL most likely via the
      collagenous domains. To identify the binding sites in HNP-1 involved in the
      binding to C1q and MBL, we used a series of overlapping synthetic linear peptides
      that spanned the entire HNP-1 sequence. Both MBL and C1q showed a dose-dependent
      binding to the same set of peptides, suggesting a similar binding site in HNP-1
      for both MBL and C1q. Strongest binding was observed to peptides containing the C
      or N-terminal part of the HNP-1 molecule. Using an ELISA based system, we
      demonstrated that HNP-1 inhibits activation of both the classical pathway and
      lectin pathway of complement. Furthermore, we demonstrated that C1q and MBL can
      form complexes with HNP-1 in solution. Together, the data indicate that HNP-1
      interacts with both C1q and MBL efficiently resulting in inhibition of both the
      classical and the lectin pathway of complement. We conclude that HNP-1 may play a
      role in protection against tissue injury during inflammatory conditions by
      inhibiting the early phase of complement activation.

PMID- 17448538
TI  - Prevalence and causes of visual impairment in rural myanmar: the Meiktila Eye
      Study.
AB  - OBJECTIVE: To determine the prevalence and causes of visual impairment in the
      Meiktila district of central, rural Myanmar. DESIGN: Population-based cross
      sectional study. PARTICIPANTS: Random, stratified, cluster sampling of the
      inhabitants 40 years of age and older from villages in the Meiktila district was
      performed; 2481 eligible participants were identified and 2076 participated in
      the study. METHODS: The ophthalmic examination included presenting and pinhole
      Snellen visual acuity with an illiterate E chart, slit-lamp examination of the
      anterior segment, and dilated stereoscopic fundus examination. The principal
      cause of visual impairment was recorded. MAIN OUTCOME MEASURES: Visual impairment
      and blindness were defined by both presenting and corrected visual acuity
      according to World Health Organization criteria: better eye < 6/18 and < 3/60,
      respectively. RESULTS: Comprehensive examinations, including Snellen visual
      acuity, were performed on 2073 participants (83.6%) The prevalence estimate of
      presenting visual impairment was 40.4% (95% confidence interval [CI], 36.1-44.7)
      and of presenting blindness was 8.1% (95% CI, 6.5-9.9). After pinhole correction,
      the corresponding prevalences were 26.8% (95% CI, 23.5-30.1) and 5.3% (95% CI,
      4.0-6.6). Cataract, uncorrected refractive error, and glaucoma were the most
      common causes of visual impairment. CONCLUSIONS: Visual impairment and blindness
      remain major public health problems in rural Myanmar. Specific programs directed
      toward reducing the cataract burden need to be implemented.

PMID- 17448539
TI  - Outcomes of bilateral cataract surgery in Tanzanian children.
AB  - OBJECTIVE: To investigate outcomes of bilateral pediatric cataract surgery in
      east Africa. DESIGN: Retrospective interventional case series. PARTICIPANTS: Two
      hundred forty-three children who underwent bilateral cataract surgery at the
      Comprehensive Community-Based Rehabilitation for Tanzania Disability Hospital
      between 2001 and 2004. METHODS: Demographic, surgical, preoperative, and
      postoperative clinical characteristics obtained from patient records were entered
      into a database (Microsoft Excel; Microsoft, Redmond, WA), and statistical
      analysis was conducted using SPSS software for Windows (SPSS, Inc., Chicago, IL).
      MAIN OUTCOME MEASURES: Postoperative visual acuities and factors affecting them
      and postoperative refraction results. RESULTS: Intraocular lenses were inserted
      in the first eyes of 232 children (149 Alcon AcrySof [Alcon Laboratories, Fort
      Worth, TX], 83 polymethyl methacrylate [PMMA]). Fifty-eight (62%) of 94 patients
      with final follow-up acuities recorded in both eyes achieved 20/60 or better in
      their better eye and 13 (13%) of 94 patients were blind. Of the various
      predictors of good visual outcome identified for children or eyes, only absence
      of preoperative blindness (odds ratio [OR], 7.3; 95% confidence interval [CI],
      3.0-18.0; P<0.0005) remained significant in a multivariate logistic regression
      model. One hundred nine (51%) of 212 refracted first eyes had early postoperative
      refractive error spherical equivalent magnitudes of 2 diopters (D) or more.
      Ninety-nine (47%) of 212 eyes had initial postoperative cylinders of 3 D or more,
      dropping to 30 (18%) of 164 of those who had later follow-up refraction. Presence
      of biometric data was not associated with smaller postoperative refractive
      errors. Eyes with AcrySof lenses were less likely (OR, 2.5; 95% CI, 1.04-6.06) to
      have more than 3 D of astigmatism at latest follow-up. AcrySof lenses also were
      more likely (OR, 2.1; 95% CI, 1.2-3.7) to be fixated in the bag than PMMA lenses.
      Acute fibrinous uveitis occurred in 30 cases (12%), and transient corneal haze
      occurred in 20 cases (8%). Twenty-seven (11%) had chronic complications, 69 (28%)
      underwent a further general anesthetic procedure, and 9 (4%) underwent yytrium
      aluminum-garnet capsulotomy. CONCLUSIONS: Preoperative blindness was the
      strongest predictor of poor postoperative visual outcome; the use of AcrySof
      lenses as opposed to PMMA lenses made in-the-bag fixation more likely and also
      reduced postoperative astigmatism.

PMID- 17448540
TI  - Interpretation of Mycobacterium tuberculosis antigen-specific IFN-gamma release
      assays (T-SPOT.TB) and factors that may modulate test results.
AB  - BACKGROUND: Data about T cell antigen-specific (ESAT-6 and CFP-10) IFN-gamma
      release assays (IGRAs) during and after completion of anti-tuberculous (TB)
      treatment are limited and highly discordant. Thus, the utility of IGRAs as a
      surrogate marker of mycobacterial burden remain unclear. METHODS: To investigate
      factors that modulate IGRA responses during anti-TB treatment we used a
      standardised assay (T-SPOT.TB) in 33 patients with culture positive tuberculosis.
      RESULTS: Significantly more patients in the early (< or = 4 months of anti-TB
      treatment) rather than the late phase (> 4 months or completed anti-TB treatment)
      had positive IGRA responses [10/12 (83%) vs 4/21 (19%); p < or = 0.01]. Thus,
      17/21 (81%) in the late phase or who had completed treatment (mean duration of
      treatment = 8.7 months) were IGRA negative, despite having robust antigen
      specific recall proliferative responses. In these 17 patients prolonged
      incubation (5 days vs overnight), use of different antigen preparations (protein
      vs peptide) and addition of endotoxin, failed to elicit positive responses.
      CONCLUSIONS: In treated TB patients the discordant IGRA data remain unexplained
      by variation in laboratory protocols and are more likely due to host or
      environmental factors. In a low burden setting IGRAs may be a promising surrogate
      marker of mycobacterial disease burden.

PMID- 17448541
TI  - Mesolimbic dopamine and cortico-accumbens glutamate afferents as major targets
      for the regulation of the ventral striato-pallidal GABA pathways by neurotensin
      peptides.
AB  - The tridecapeptide neurotensin (NT) acts in the mammalian brain as a primary
      neurotransmitter or neuromodulator of classical neurotransmitters. Morphological
      and functional in vitro and in vivo studies have demonstrated the existence of
      close interactions between NT and dopamine both in limbic and in striatal brain
      regions. Additionally, biochemical and neurochemical evidence indicates that in
      these brain regions NT plays also a crucial role in the regulation of the
      aminoacidergic signalling. It is suggested that in the nucleus accumbens the
      regulation of prejunctional dopaminergic transmission induced by NT may be
      primarily due to indirect mechanism(s) involving mediation via the aminoacidergic
      neuronal systems with increased glutamate release followed by increased GABA
      release in the nucleus accumbens rather than a direct action of the peptide on
      accumbens dopaminergic terminals. The neurochemical profile of action of NT in
      the control of the pattern of dopamine, glutamate and GABA release in the nucleus
      accumbens differs to a substantial degree from that shown by the peptide in the
      dorsal striatum. The neuromodulatory NT mechanisms in the regulation of the
      ventral striato-pallidal GABA pathways are discussed and their relevance for
      schizophrenia is underlined.

PMID- 17448542
TI  - Utility of the concept of minor depressive disorder: evidence from a large rural
      community sample in a developing country setting.
AB  - BACKGROUND: Evidence on the utility of the minor depressive disorder diagnostic
      construct in rural communities and developing countries is scarce. AIM: To assess
      the utility and validity of definitive minor depressive disorder in Ethiopia by
      determining its impact and sociodemographic correlates. METHODS: Assessment of
      68,378 adults, aged 15-49 years, living in a largely rural district in Ethiopia
      using the Composite International Diagnostic Interview. RESULTS: The lifetime
      prevalence of minor depressive disorder was 2.2% (95% CI=2.1%, 2.3%). Age,
      marital status, education and unemployment independently predicted minor
      depressive disorder. Over 80% of cases used health services, 55.1% experienced
      persistent thoughts of death and 14.6% attempted suicide. LIMITATION: Findings
      are based on lifetime estimates. CONCLUSIONS: Minor depressive disorder is an
      important public health problem in rural Ethiopia, as shown by the associated
      high health service use and risk behaviour. Sociodemographic correlates suggest
      aetiological continuity with major depression. Thus our findings extend the
      clinical and public health utility of this diagnostic construct to rural
      community and developing country settings.

PMID- 17448543
TI  - Job strain, burnout, and depressive symptoms: a prospective study among dentists.
AB  - BACKGROUND: Burnout has been presented as an antecedent of depression, but
      longitudinal data are lacking. We investigated whether burnout mediates the
      association between job strain and depressive symptoms. METHODS: Two surveys were
      conducted. In 2003, 71% of Finnish dentists were reached, and the response rate
      of the 3-year follow-up was 84% (n=2555). Burnout was measured with the Maslach
      Burnout Inventory and depressive symptoms with the Beck Depression Inventory. The
      sequences 'job strain-burnout-depressive symptoms' and 'job strain-depressive
      symptoms-burnout' were investigated with logistic regression analyses. RESULTS:
      Of the burnout sufferers without depressive symptoms at baseline, 23% reported
      depressive symptoms at follow-up. The adjusted odds ratio of burnout for
      depressive symptoms was 2.6 (95% CI 2.0-3.5). The effect of job strain on
      depressive symptoms had an OR of 3.4 (95% CI 2.0-5.7), but it disappeared when
      adjusted for burnout. Of those who had depressive symptoms without burnout at
      baseline, 63% had burnout at follow-up. The adjusted odds ratio of depressive
      symptoms for burnout was 2.2 (95% CI 1.4-3.4). The effect of job strain on
      burnout had an OR of 27.9 (95% CI 6.5-120.2) for the men and 4.9 (95% CI 2.5-9.6)
      for the women. These effects remained significant after adjustment for depressive
      symptoms. LIMITATIONS: The study was conducted among one occupational group.
      CONCLUSIONS: There is a reciprocal relationship between burnout and depressive
      symptoms. Job strain predisposes to depression through burnout. In comparison,
      job strain predisposes to burnout directly and via depression.

PMID- 17448544
TI  - T- and B-lymphocytes in patients with schizophrenia in acute psychotic episode
      and the course of the treatment.
AB  - Schizophrenia is associated with alterations of the immune system. There are,
      however, only limited data dealing with immune parameters in unmedicated
      schizophrenic patients and the course of these parameters during treatment. In
      this study, we monitored CD19+ (B)- and CD3+ (T)-lymphocytes in the course of
      antipsychotic treatment. Forty patients diagnosed with an acute exacerbation of
      schizophrenia were tested before and after 3 days, 2 weeks, 4 weeks and 3 months
      of treatment with antipsychotics. The percentages of CD19+- and CD3+ -lymphocytes
      were analysed by flow cytometry using fluorescence conjugated anti-CD19 and anti
      CD3 antibodies. Twenty healthy volunteers served as controls. In the acute state
      of psychosis, a significant reduction of the CD3+ -lymphocyte subpopulation was
      observed, while the percentage of CD19(+)-lymphocytes was increased. Both
      subpopulations levelled to those of the control group in the course of treatment.
      As expected, the levels of the immune parameters did not change in the healthy
      controls during the course of the study. The observed alterations of the CD19+ -
      and CD3+ -lymphocytes in the acute state of psychosis especially in patients with
      the paranoid subtype of schizophrenia, and the "normalization" during the
      observation period are discussed under the aspect of the immune hypothesis of
      schizophrenia, in particular of the type-1/type-2 imbalance hypothesis.

PMID- 17448545
TI  - Immunobiological role of llama heavy-chain antibodies against a bacterial beta
      lactamase.
AB  - In 1993, a fraction of antibodies (Abs) devoid of L chain was found naturally
      occurring in the Camelidae. They were found to lack L chains, as well as the
      first constant heavy-chain domain (CH(1)) and therefore they were named "heavy
      chain Abs" (HCAbs). Subsequent studies focused on the functional, structural and
      biochemical properties of recombinant variable fragments (rVHHs) of HCAbs. It was
      stated that rVHHs have an augmented capacity to interact with "partially hidden"
      epitopes, like enzymes active sites, and have an increased stability to thermal
      and chemical aggression. It has been suggested that these unconventional Abs
      could represent an evolutionary advantage, being more efficient than conventional
      Abs to inhibit microbial enzymes, and thus exerting a more protective immune
      response against pathogens. The present work focuses on the immunobiological role
      of HCAbs, in their capacity to inhibit microbial enzymes. Two animal models were
      selected, comprising a model for common vertebrates without HCAbs (rabbits), and
      a model for vertebrates with both conventional and unconventional Abs (Lama
      glama). A recombinant bacterial beta-lactamase (CTX-M-2) was selected as the
      microbial enzymatic antigen. After conventional immunization schedules, neither
      serum titers nor serum inhibitory capacity showed significant differences when
      rabbits and llamas were compared. These results indicate that the a priori
      assumption that the adaptive immune system of camelids could be better "prepared"
      to respond to bacterial enzymes because of the presence of HCAbs, is not always
      accurate. Furthermore, when the different llama antibody isotypes and subclasses
      were purified, it was demonstrated that the inhibitory capacity of total serum
      was due exclusively to IgG(1). HCAbs not only failed to inhibit CTX-M-2, but
      instead they activated its enzymatic activity. Altogether, these results indicate
      that the hypotheses extrapolated from the rVHHs properties need to be revised;
      the real role of HCAbs in vivo remains unknown, as well as their evolutionary
      cause.

PMID- 17448546
TI  - A functional magnetic resonance imaging study of the body schema using full human
      line-drawing figures in an on-line verbal naming and localization task of single
      body part words.
AB  - Naming and localization of individual body part words to a high-resolution line
      drawing of a full human figure was tested in a mixed-sex sample of nine right
      handed subjects. Activation within the superior medial left parietal cortex and
      bilateral dorsolateral cortex was consistent with involvement of the body schema
      which is a dynamic postural self-representation coding and combining sensory
      afference and motor efference inputs/outputs that is automatic and nonconscious.
      Additional activation of the left rostral occipitotemporal cortex was consistent
      with involvement of the neural correlates of the verbalizable body structural
      description that encodes semantic and categorical representations to animate
      objects such as full human figures. The results point to a highly distributed
      cortical representation for the encoding and manipulation of body part
      information and highlight the need for the incorporation of more ecologically
      valid measures of body schema coding in future functional neuroimaging studies.

PMID- 17448547
TI  - In vitro analysis of the bioavailability of six metals via the gastro-intestinal
      tract of the rainbow trout (Oncorhynchus mykiss).
AB  - An in vitro gut sac technique was used to compare the uptake rates of essential
      (copper, zinc and nickel) and non-essential metals (silver, cadmium and lead) at
      50 micromol L(-1) each (a typical nutritive level in solution in chyme) in the
      luminal saline in four sections of the gastro-intestinal tract (stomach,
      anterior, mid and posterior intestines) of the freshwater rainbow trout. Cu, Zn,
      Cd and Ag exhibited similar regional patterns: on an area-specific basis, uptake
      rates for these metals were highest in the anterior intestine, lowest in the
      stomach, and approximately equal in the mid and posterior intestinal segments.
      When these rates were converted to a whole animal basis, the predominance of the
      anterior intestine increased because of its greater area, while the contribution
      of the stomach rose slightly to approach those of the mid and posterior
      intestines. However, for Pb and Ni, area-specific and whole organism transport
      rates were greatest in the mid (Pb) and posterior (Ni) intestines. Surprisingly,
      total transport rates did not differ appreciably among the essential and non
      essential metals, varying only from 0.025 (Ag) to 0.050 nmol g(-1)h(-1) (Ni),
      suggesting that a single rate constant can be applied for risk assessment
      purposes. These rates were generally comparable to previously reported uptake
      rates from waterborne exposures conducted at concentrations 1-4 orders of
      magnitude lower, indicating that both routes are likely important, and that gut
      transporters operate with much lower affinity than gill transporters. Except for
      Ni, more metal was bound to mucus and/or trapped in the mucosal epithelium than
      was transported into the blood space in every compartment except the anterior
      intestine, where net transport predominated. Overall, mucus binding was a
      significant predictor of net transport rate for every metal except Cd, and the
      strongest relationship was seen for Pb.

PMID- 17448548
TI  - Effects of lead, molybdenum, rubidium, arsenic and organochlorines on
      spermatogenesis in fish: monitoring at Mekong Delta area and in vitro experiment.
AB  - To estimate the influence of water contaminants on fish reproduction in the
      Mekong Delta area, we sampled cultivated male catfish (Pangasianodon
      hypophthalmus), investigated testicular development, and measured persistent
      organic pollutants (POPs) and trace element levels in muscle and liver,
      respectively. Various testes sizes were observed although sampling took place
      during a short period. Histological analysis revealed that all developmental
      stages of germ cells were observed in catfish with large testis, whereas only
      necrotic spermatogonia but no other germ cells were observed in catfish with
      small testis. In small testis, furthermore, vacuolization and hypertrophy of
      Sertoli cells were observed. Measurement of POPs in muscle and trace elements in
      liver demonstrated that there were negative correlations between GSI and the
      concentrations of Pb, Mo, Rb and As. To clarify possible direct effects of Pb,
      Mo, Rb and As on spermatogenesis in fish, we investigated the effects of these
      trace elements on spermatogenesis using in vitro testicular organ culture of
      Japanese eel (Anguilla japonica). Treatment with each of the trace elements alone
      did not affect spermatogenesis. However, treatment with 10(-7)M of Pb, 10(-5) and
      10(-4)M of Mo, 10(-5)-10(-3)M of Rb or 10(-5)M of As inhibited the
      spermatogenesis induced by 11-ketotestosterone (11KT). Furthermore, treatment
      with 10(-4)M of As in combination with 11KT caused necrosis of testicular
      fragments. Taken together, these results are consistent with the hypothesis that
      Pb, Mo, Rb and As can exert inhibitory effects on spermatogenesis in catfish
      inhabiting the Mekong Delta area.

PMID- 17448550
TI  - Refractory vasospastic angina causing myocardial infarction and VF arrest
      requiring combined medical, electrophysiological, percutaneous and surgical
      intervention--a case report.

PMID- 17448551
TI  - First heart sound and opening snap in patients with mitral valve disease.
      Phonocardiographic and pathomorphologic study.
AB  - We investigated correlation between mitral valve morphology and first heart sound
      (S(1)) and opening snap (OS) amplitude. The analysis revealed negative
      correlation between the OS amplitude and the area of calcification and the mitral
      orifice area. We also found negative correlation between the S(1) intensity and
      the area of calcification.

PMID- 17448552
TI  - Role of intravascular ultrasound in the management of intracoronary dislodged
      stent.
AB  - We describe a nonagenarian patient in whom a paclitaxel-eluting stent was lost
      during an attempt of direct stent implantation at the distal right coronary
      artery after removal of the guide-wire. The potential usefulness of intravascular
      ultrasound in the management of this complication is illustrated. The dislodged
      stent could not be located by fluoroscopy. However, intravascular ultrasound
      allowed to find the undeployed stent at the proximal segment of the right
      coronary artery. It showed that the guide-wire was placed outside the lost stent
      lumen and this undeployed stent was crushed against a previously implanted stent
      by another stent with optimal intravascular ultrasound-guided implantation.

PMID- 17448553
TI  - Pericardial effusion with elevated serum carbohydrate antigen 125 levels and
      ovarian tumor mass.

PMID- 17448554
TI  - Mortality, lifestyle and socio-economic status.
AB  - This paper uses the British Health and Lifestyle Survey (1984-1985) data and the
      longitudinal follow-up of May 2003 to investigate the determinants of premature
      mortality in Great Britain and the contribution of lifestyle choices to socio
      economic inequality in mortality. A behavioural model, which relates premature
      mortality to a set of observable and unobservable factors, is considered. A
      maximum simulated likelihood (MSL) approach for a multivariate probit (MVP) is
      used to estimate a recursive system of equations for mortality, morbidity and
      lifestyles. Health inequality is explored using the Gini coefficient and a
      decomposition technique. The decomposition analysis for predicted mortality shows
      that, after allowing for endogeneity, lifestyles contribute strongly to
      inequality in mortality, reducing the direct role of socio-economic status. This
      contradicts the view, which is widely held in epidemiology, that lifestyles make
      a relatively minor contribution to observed socio-economic gradients in health.

PMID- 17448555
TI  - Reduction in event-related alpha attenuation during performance of an auditory
      oddball task in schizophrenia.
AB  - EEG frequency-domain analyses have demonstrated that cognitive performance
      produces a reduction in alpha activity, i.e., alpha attenuation, such as event
      related desynchronization (ERD), reflecting brain activation. To examine whether
      schizophrenic patients have abnormalities in frequency-domain, event-related
      alpha attenuation, as well as in time-domain EEG phenomena, such as event-related
      potential, we compared alpha power change and P300 elicited simultaneously in
      response to the presentation of target tones in an auditory oddball paradigm
      between patients with schizophrenia and normal control subjects. In both patients
      and controls, alpha power was smaller during the time window of 512 ms following
      targets than following non-targets, particularly at the parietal and the
      posterior temporal locations (Pz, T5, and T6). The size of alpha attenuation
      measured as percent reduction in alpha power produced by targets relative to non
      targets was smaller in patients than in controls at the posterior temporal
      locations. The size of alpha attenuation showed no correlation with P300
      amplitude or latency in either patients or controls. Furthermore, in patients,
      the size of alpha attenuation showed no correlation with symptom severity, while
      P300 amplitude was correlated negatively with the positive subscale score of the
      Positive and Negative Syndrome Scale. These findings suggest that the symptom
      independent reduction in event-related alpha attenuation in schizophrenia may be
      useful as an electrophysiological index of the impairment of neural processes
      distinct from that indexed by symptom-dependent P300 abnormalities.

PMID- 17448556
TI  - Is conceptual priming for environmental sounds obligatory?
AB  - Conceptual priming for environmental sounds was examined in two tasks using pairs
      of a visually presented word (prime stimulus) and an environmental sound (probe
      stimulus). In the first task (physical task) participants had to indicate to
      which ear the sound was presented. In the second task (semantic task)
      participants judged whether word and sound of a pair fitted together.
      Participants switched between the two tasks randomly, with the color of the word
      indicating each trial which task was to be performed. An N400-effect for
      unrelated compared to related sounds was observed in both tasks, although
      reaction times did not reveal a statistically reliable priming effect. The
      results show that environmental sounds are processed conceptually even if the
      task does not require analysis of stimulus meaning.

PMID- 17448557
TI  - A novel variant of Thermotoga neapolitana beta-glucosidase B is an efficient
      catalyst for the synthesis of alkyl glucosides by transglycosylation.
AB  - Alkyl glycosides are surfactants with good biodegradability and low toxicity,
      attractive to produce by an enzymatic method to get a well-defined product. In
      this paper, we report a novel thermostable variant of a family 3 beta-glucosidase
      to be an efficient catalyst in alkyl-glucoside forming reactions using
      transglycosylation with hexanol or octanol as the acceptor molecule. The enzyme
      has an apparent optimum for hydrolysis at 90 degrees C, which coincides with its
      unfolding temperature. The total activity is lower at lower temperature (60
      degrees C), but the ratio of alcoholysis/hydrolysis is slightly more favourable.
      This ratio is however more heavily influenced by the water content and the pH.
      Optimal reaction conditions for hexyl glucoside synthesis from p-nitrophenyl-beta
      glucopyranoside were a water/hexanol two-phase system containing 16% (v/v) water,
      pH 5.8, and a temperature of 60 degrees C. Under these conditions, the total
      initial reaction rate was 153 micromol min(-1)mg(-1) and the
      alcoholysis/hydrolysis ratio was 5.1. Comparing with alcoholysis/hydrolysis
      ratios of other beta-glycosidases, TnBgl3B can be considered to be a very
      promising catalyst for alkyl glucoside production.

PMID- 17448558
TI  - Intracellular localization of the SARS coronavirus protein 9b: evidence of active
      export from the nucleus.
AB  - Open reading frame 9b (ORF 9b) encodes a 98 amino acid group-specific protein of
      severe acute respiratory syndrome (SARS) coronavirus (CoV). It has no homology
      with known proteins and its function in SARS CoV replication has not been
      determined. The N-terminal part of the 9b protein was used to raise polyclonal
      antibodies in rabbits, and these antibodies could detect 9b protein in infected
      cells. We analyzed the sub-cellular localization of recombinant 9b protein using
      fluorescence microscopy of live transfected cells and indirect immunofluorescence
      of transfected fixed cells. Our findings indicate that the 9b protein is exported
      outside of a cell nucleus and localizes to the endoplasmic reticulum. Our data
      also suggest that the 46-LRLGSQLSL-54 amino acid sequence of 9b functions as a
      nuclear export signal (NES).

PMID- 17448559
TI  - Identification and characterization of Raspberry mottle virus, a novel member of
      the Closteroviridae.
AB  - Raspberry mosaic is one of the most important viral diseases of raspberry. Four
      virus and virus-like agents, two of which are poorly characterized, have been
      implicated in the disease complex based on symptom development in Rubus
      indicators. Three novel viruses were identified in a red raspberry plant that
      caused typical raspberry mosaic symptoms when grafted onto indicators. This
      communication focuses on one of these viruses, Raspberry mottle virus (RMoV), a
      new member of the family Closteroviridae. The complete nucleotide sequence of
      RMoV has been determined and exceeds 17 kilobases encoding 10 genes. The genome
      organization of RMoV is similar to that of Beet yellows virus, the type member of
      the Closterovirus genus, and phylogenetic analysis using the polymerase conserved
      motifs and the heat shock protein 70 homolog revealed a close relationship of
      RMoV with Strawberry chlorotic fleck associated virus and Citrus tristeza virus,
      which suggests the possibility of an aphid vector. The virus was detected in
      symptomatic raspberry plants in production areas in mixed infections with several
      other viruses, indicating that RMoV may impact raspberry production.

PMID- 17448560
TI  - Increased fat absorption and impaired fat clearance cause postprandial
      hypertriglyceridemia in Spontaneously Diabetic Torii rat.
AB  - In diabetes, postprandial hyperlipidemia is recognized as a risk factor for
      premature atherosclerosis and following cardiovascular disease. In the present
      study, features of fat absorption and clearance were examined to clarify the
      lipid metabolism of Spontaneously Diabetic Torii (SDT) rats. Olive oil was orally
      administered to evaluate increase of blood triglyceride (TG) level. Mesenteric
      lymph chylomicron TG was also measured. mRNAs of enzymes and transfer protein
      related to TG metabolism and histopathological changes were evaluated. In an oil
      loading test, elevation of TG in plasma and lymph chylomicron was increased in
      SDT rats. Interestingly, SDT rats showed elevation of plasma TG after oil loading
      and relatively low epididymal fat lipoprotein lipase (LPL) mRNA expression even
      at the pre-diabetic state without increase of TG absorption from intestine. In
      the diabetic state, intestines of SDT rats were hypertrophic and expressed mRNAs
      of enzymes and transfer protein related to TG absorption highly. From these
      results, it seems that intestinal abnormalities related to
      hypoinsulinemia/hyperglycemia cause postprandial hypertriglyceridemia in SDT
      rats. In addition, our findings suggest that SDT rats have impaired lipid
      catabolism antecedent to hypoinsulinemia/hyperglycemia. These characteristics of
      SDT rats can be useful in studies of diabetic hypertriglyceridemia and TG
      metabolism.

PMID- 17448561
TI  - Lifestyle factors and incident metabolic syndrome. The Tromso Study 1979-2001.
AB  - OBJECTIVES: To assess the relationship between lifestyle characteristics and
      incident metabolic syndrome. METHODS: A total of 17,014 men and women without the
      metabolic syndrome at baseline who participated in at least two of four surveys
      between 1979-1980 and 2001 were included in this population based longitudinal
      study in the municipality of Tromso, Norway. At each survey the participants went
      through a physical examination, completed two questionnaires, and blood samples
      were taken. The metabolic syndrome was defined according to the Adult Treatment
      Panel III criteria with modifications. RESULTS: The age-adjusted incidence rates
      of the metabolic syndrome per 1000 person-years for people age 20-56 years were
      10.0 in men and 8.7 in women. The metabolic syndrome risk significantly increased
      with age in women, but not in men. Leisure-time physical activity was inversely
      related to the metabolic syndrome. Smoking more than 20 cigarettes per day was
      associated with an increased risk compared to non-smokers. The hazard ratios (95%
      confidence intervals) were 1.27 (1.04-1.54) and 1.40 (1.02-1.92) in men and
      women, respectively. Alcohol intake and education were inversely associated with
      metabolic syndrome in women but not in men. CONCLUSIONS: Physical inactivity and
      heavy smoking increased the metabolic syndrome incidence in men and women. Low or
      no intake of alcohol was also associated with increased risk, but in women only.

PMID- 17448562
TI  - Educational program for diabetic patients in Korea--multidisplinary intensive
      management.
AB  - The socioeconomic burden of type 2 diabetes and its complications has become a
      big social issue in Korea. And so, the proper management of diabetes in terms of
      its prevention and management of complications are considered the most important
      tasks in our healthcare system and these can be accomplished through the
      multidisciplinary program. Our program is composed of separate educational
      programs for in-patients and out-patients, individualized teaching, and group
      teaching. In order to maintain such a program, there need systemic interactions
      among the team members, including endocrinologists, nurses, dieticians,
      pharmacists, and social workers. The optimal way to control diabetes can be
      achieved through interactions between members of the diabetes management team and
      the patient. For the patient, this is expected to lead to a better glycemic
      control, prevention of diabetes complications, and sparing of medical expenses as
      well. As for the healthcare providers, physicians are able to treat their
      patients more efficiently. Thus, both the patient and the healthcare centers can
      benefit from this multidisciplinary educational program. Diabetes educational
      program should be a basis for the management of diabetes.

PMID- 17448563
TI  - Relevance of casual undetected hyperglycemia among high-risk individuals for
      developing diabetes.
AB  - To assess the relevance of unrecognized hyperglycemia among high-risk subjects
      for developing diabetes a cross-sectional study was carried out. Subjects aged 40
      75 years with (high-risk group) and without (control group) history of impaired
      glucose metabolism underwent a 2h-oral glucose tolerance test (OGTT). All
      individuals with diabetes diagnostic criteria and all controls with glucose
      abnormalities at OGTT were excluded. An individualized 48-h continuous glucose
      monitoring (CGM) calibrated by fasting plasma glucose was performed. The
      microdialysis-based biosensor recordings were computerized in order to identify
      continuous glucose profiles. Of the 121 monitored subjects, 104 were finally
      analyzed (56.7% female, 57.8 years, BMI=29.2, A1C=4.9%, HOMA index=2.5). Glucose
      profiles corresponded to 31 controls (29.8%), 32 high-risk individuals with
      normal OGTT (30.8%) and 41 (39.4%) with hyperglycemia at OGTT. The recordings
      defined as hyperglycemia (fasting >or=6.1 mmol/l, non-fasting >or=7.8 mmol/l)
      appeared during an average of 1.4h, 4.9h and 7.6h (3.9%, 13.9% and 19% of the CGM
      time), respectively. The highest percentage of impaired CGM registers
      corresponded to the fasting period. Nevertheless, the longest duration
      corresponded to the non-fasting period. The CGM evidenced a relevant degree of
      casual undetected hyperglycaemia among high-risk individuals.

PMID- 17448564
TI  - Functional evaluation of the type 1 diabetes (T1D) susceptibility candidate
      genes.
AB  - Progress has been made in investigating the genetic factors involved in type 1
      diabetes (T1D) development for the past few years. While Linkage disequilibrium
      (LD) mapping has been useful for both the confirmation and fine-mapping of
      susceptibility intervals, as well as identification of etiological mutations,
      identification of specific disease genes has been a challenge and limited to
      known candidate genes. The overall risk for T1D from the HLA DR and DQ molecules
      (IDDM1) is determined by combinations of polymorphic alleles. Functional studies
      indicate that the susceptible and protective HLA-DR and -DQ bind and present non
      overlapping peptides. Although consistent linkage evidence was reported for the
      susceptibility intervals IDDM2, IDDM5 and IDDM12, evidence for most other
      intervals varies in different data sets. The variable number of tandem repeats at
      the 5' end of the insulin gene (IDDM2) regulates insulin expression in the
      thymus. Studies on IDDM5 have led to the discovery of a novel polymorphism 163 A-
      >G (M55V) in SUMO4 gene, which was found to be associated with T1D patients with
      Asian origin. Functionally SUMO4 conjugates to IkBalpha and negatively regulates
      NFkB transcriptional pathway. The M55V substitution reduces the sumoylation
      activity of the V55 variant, which resulted in higher NFkB dependent
      transcriptional activity. The polymorphisms of the cytotoxic T lymphocyte antigen
      4 gene (CTLA4, IDDM12) encoding a regulatory molecule in the immune system
      associate with T1D and autoimmune thyroid diseases (ATD). The 3' untranslated
      region of this gene determines the level of soluble CTLA-4. Genetic mapping of
      variants conferring a small disease risk can identify pathways in complex
      disorders, as evidenced by quantitative alterations of candidate genes
      contributing to autoimmune tissue destruction. Moreover, the identification of
      two transcription factors that, when mutated, are responsible for severe
      autoimmune disease is leading to a better understanding of T cell tolerance. Both
      AIRE and Foxp3, identified initially via their association with genetically
      manipulated mice, are involved in tolerance induction in humans. Although
      mutations in these genes may cause rare but serious diseases, it is likely that
      other transcription factors will contribute to the genetic load that predisposes
      certain individuals to disease.

PMID- 17448565
TI  - Muscle GLUT4 in cirrhosis.
AB  - BACKGROUND/AIMS: The insulin-dependent glucose transporter GLUT4 mediates 50-80%
      of whole body glucose uptake, but its relation to the frequent glucose
      intolerance in patients with liver cirrhosis is unknown. METHODS: Thirty patients
      and seven healthy controls underwent a 2-h oral glucose tolerance test and later
      a muscle biopsy. Levels of GLUT4 total protein and mRNA content were determined
      in muscle biopsies by polyclonal antibody labelling and RT-PCR, respectively.
      RESULTS: GLUT4 protein content in the cirrhosis group was not different from that
      of the controls, but at variance with the control subjects it correlated closely
      with measures of glucose tolerance (R(2)=0.45; p=0.003). GLUT4 mRNA of the
      patients with cirrhosis was reduced to 56% of control value (95% ci: 27-86%;
      p=0.015) and was inversely related to the level of basal hyper-insulinemia
      (R(2)=0.39; p=0.004). CONCLUSIONS: In cirrhosis GLUT4 protein content was
      quantitatively intact, while limiting glucose tolerance. This indicates loss of
      redundancy of the major glucose transport system, possibly related to the
      markedly decreased expression of its gene. Hyper-insulinemia may be a primary
      event. Our findings implicate the muscular GLUT4 system in the glucose
      intolerance of liver cirrhosis by a mechanism different from that in diabetes.

PMID- 17448566
TI  - Altered expression of TLR homolog RP105 on monocytes hypersensitive to LPS in
      patients with primary biliary cirrhosis.
AB  - BACKGROUNDS/AIMS: Toll-like receptors (TLRs) have emerged as a key component of
      the innate immune system that triggers antimicrobial responses. Altered monocyte
      responses to ligands for TLRs have been reported in patients with primary biliary
      cirrhosis (PBC), yet the precise mechanism remains unknown. METHODS: We
      investigated in vitro responses to a TLR4 ligand, lipopolysaccharide (LPS), using
      peripheral blood mononuclear cells and monocytes from 25 patients with PBC, 10
      patients with chronic viral hepatitis (CVH), and 20 healthy individuals. RESULTS:
      After stimulation with LPS, we found significantly higher amounts of IL-1beta, IL
      6, and IL-8 production in PBC patients. Through the TLR4 signaling pathway,
      activation of NF-kappaB and expression of MyD88 mRNA were significantly increased
      in PBC patients, and the level of TLR4 expression was significantly increased on
      PBC monocytes as compared with CVH patients and controls. Of significance, the
      surface expression of RP105, which has recently been shown to be involved in
      negative regulation of TLR4 signaling, on PBC monocytes was significantly
      decreased in comparison with CVH patients (P=0.016) and controls (P<0.001).
      CONCLUSIONS: These results suggest that expression of RP105 and TLR4 is altered
      on PBC monocytes, which appear to be hypersensitive to LPS, resulting in
      increased secretion of pro-inflammatory cytokines.

PMID- 17448567
TI  - Intestinal bile salt absorption in Atp8b1 deficient mice.
AB  - BACKGROUND/AIMS: Mutations in the ATP8B1 gene can cause Progressive Familial
      Intrahepatic Cholestasis type 1. We have previously reported that
      Atp8b1(G308V/G308V) mice, a model for PFIC1, have slightly, but significantly,
      higher baseline serum bile salt (BS) concentrations compared to wt mice. Upon BS
      feeding, serum BS concentrations strongly increased in Atp8b1-deficient mice.
      Despite these findings, we observed only mildly impaired canalicular BS
      transport. In the present report we tested the hypothesis that
      Atp8b1(G308V/G308V) mice hyperabsorb BS in the intestine during BS feeding.
      METHODS: Intestinal BS absorption was measured in intestinal perfusion and in
      intestinal explants. In addition, we measured BS concentrations in portal blood.
      Ileal expression of the Fxr-targets Asbt, Ilbp and Shp was assessed. RESULTS: In
      wt and Atp8b1(G308V/G308V) mice, intestinal taurocholate absorption is primarily
      mediated by the ileal bile salt transporter Asbt. Neither of the experimental
      systems revealed enhanced absorption of BS in Atp8b1(G308V/G308V) mice compared
      to wt mice. In line with these observations, we found no difference in the ileal
      protein expression of Asbt. Induction of Shp expression during BS feeding also
      demonstrated that Fxr signalling is intact in Atp8b1(G308V/G308V) mice.
      CONCLUSIONS: The accumulation of BS in plasma of Atp8b1(G308V/G308V) mice during
      BS feeding is not caused by increased intestinal BS absorption.

PMID- 17448568
TI  - Liver-specific HBsAg transgenic mice are over-sensitive to Poly(I:C)-induced
      liver injury in NK cell- and IFN-gamma-dependent manner.
AB  - BACKGROUND/AIMS: The role of natural killer (NK) cells in the development of
      hepatitis B virus (HBV)-associated liver injury remains obscure. In this study,
      we elucidated the role of NK cells in liver injury of HBsAg transgenic mice (HBs
      B6), a mimic of human healthy chronic HBsAg carriers, triggered by
      polyinosinic:polycytidylic acid [Poly(I:C)]. METHODS: HBs-B6 or wild B6 mice were
      intraperitoneally injected with Poly(I:C) at different doses. Liver injury was
      evaluated by serum transaminase activity and histopathologic changes. RESULTS:
      HBs-B6 mice were over-sensitive to Poly(I:C)-induced liver injury, which was
      absolutely dependent on the presence of NK cells and IFN-gamma produced by
      intrahepatic NK cells. Much stronger IFN-gamma receptor expression was observed
      on hepatocytes of HBs-B6 mice, which was significantly enhanced by Poly(I:C)
      injection. Treatment with IFN-gammain vitro triggered much higher activation of
      downstream signals (pSTAT1-IRF-1) in hepatocytes of HBs-B6 mice. Depletion of
      Kupffer cells and neutralization of endogenous IL-12 did not affect Poly(I:C)
      induced over-sensitive liver injury in HBs-B6 mice. CONCLUSIONS: NK cells played
      a critical role in an IFN-gamma dependent, Kupffer cell- and IL-12-independent
      manner in over-sensitive liver injury triggered by Poly(I:C) in murine chronic
      HBsAg carriers.

PMID- 17448569
TI  - The effect of a high-protein, low glycemic-load diet versus a conventional, high
      glycemic-load diet on biochemical parameters associated with acne vulgaris: a
      randomized, investigator-masked, controlled trial.
AB  - BACKGROUND: No previous study has sought to examine the influence of dietary
      composition on acne vulgaris. OBJECTIVE: We sought to compare the effect of an
      experimental low glycemic-load diet with a conventional high glycemic-load diet
      on clinical and endocrine aspects of acne vulgaris. METHODS: A total of 43 male
      patients with acne completed a 12-week, parallel, dietary intervention study with
      investigator-masked dermatology assessments. Primary outcomes measures were
      changes in lesion counts, sex hormone binding globulin, free androgen index,
      insulin-like growth factor-I, and insulin-like growth factor binding proteins.
      RESULTS: At 12 weeks, total lesion counts had decreased more in the experimental
      group (-21.9 [95% confidence interval, -26.8 to -19.0]) compared with the control
      group (-13.8 [-19.1 to -8.5], P = .01). The experimental diet also reduced weight
      (P = .001), reduced the free androgen index (P = .04), and increased insulin-like
      growth factor binding protein-1 (P = .001) when compared with a high glycemic
      load diet. LIMITATIONS: We could not preclude the role of weight loss in the
      overall treatment effect. CONCLUSION: This suggests nutrition-related lifestyle
      factors play a role in acne pathogenesis. However, these preliminary findings
      should be confirmed by similar studies.

PMID- 17448570
TI  - Food safety knowledge, attitudes and practices of mothers: findings from focus
      group studies in South India.
AB  - In India, most of the diarrhoeal deaths among children (<5 years) are attributed
      to food and water contamination. Mothers are usually the final line of defence
      against food borne illnesses. Thus, the role of mothers in ensuring food safety
      at homes is well accepted. There are hardly any studies in India to understand
      their knowledge, attitudes and practices on food safety. The present study was an
      attempt in this direction. A total of 32 Focus Group Discussions were carried out
      with mothers of children <5 years in 16 districts from all the four South Indian
      states. The findings reveal that food safety awareness and practices are good
      among mothers perhaps due to the Indian food ethos passed on to them through
      generations. Home cooked foods are considered to be safer than prepared foods
      bought from outside. Many mothers were aware of the common food adulterants but
      do not bother to complain or take action. There is a need to create enabling
      environment with improved access to potable water, sanitation and cooking fuel.
      Spreading awareness about checking food labels and reporting to the health
      authorities in case of food poisoning or adulteration is also the need of the
      hour. The Anganwadi Centres can be the focal points for imparting food safety
      education to the mothers.

PMID- 17448571
TI  - Structure of food attitudes: replication of Aikman, Crites, and Fabrigar (2006).
AB  - Recent research by Aikman, Crites, and Fabrigar [(2006). Beyond affect and
      cognition: Identification of the informational bases of food attitudes. Journal
      of Applied Social Psychology, 36, 340-382] suggests that food attitudes are
      comprised of five distinct informational bases: positive affect (e.g., calm,
      comforted), negative affect (e.g., guilty, ashamed), abstract cognitive qualities
      (e.g., healthy, natural), general sensory qualities (e.g., taste, smell), and
      specific sensory qualities (e.g., salty, greasy). The Aikman et al. (2006)
      research was conducted at a university on the US-Mexican border and consisted
      primarily of self-reported Latino participants. The present research replicates
      the previously identified food attitude structure at a university in the
      Northeast US with a sample primarily composed of self-reported Anglo American
      participants.

PMID- 17448572
TI  - Enhanced proteasome-dependent degradation of the CDK inhibitor p27(kip1) in
      immortalized lymphocytes from Alzheimer's dementia patients.
AB  - Cyclin-dependent kinase inhibitor p27(kip1) (p27), a critical determinant for
      cell cycle progression, is an important regulation target of mitogenic signals.
      We have recently reported the existence of a molecular link between decreased p27
      levels and enhanced phosphorylation of pRb protein and proliferation of
      immortalized lymphocytes from Alzheimer's disease (AD) patients. These cell cycle
      disturbances might be considered systemic manifestations, which mirror changes
      thought to occur in the brain, where post-mitotic neurons have been shown to
      display various cell cycle markers prior to degeneration. This work was
      undertaken to delineate the molecular mechanisms underlying the p27 down
      regulation associated with AD. To this end, we evaluated the p27 protein
      stability in control and AD lymphoblasts. Half-life of p27 protein was markedly
      reduced in lymphoblasts from AD patients compared with that in control cells. The
      increased phosphorylation of p27 at Thr187, rather than changes in the 26S
      proteasome activity, is likely responsible for the enhanced degradation of p27 in
      AD cells. The serum-induced enhanced proliferation of AD lymphoblasts and
      decreased levels of p27 were abrogated by calmodulin (CaM) antagonists. The
      findings presented here suggest that Ca(2+)/CaM-dependent overactivation of
      PI3K/Akt signaling cascade in AD cells, plays an important role in regulating p27
      abundance by increasing its degradation in the ubiquitin-proteasome pathway.

PMID- 17448573
TI  - Synthesis, biological evaluation and molecular modeling studies of arylidene
      thiazolidinediones with potential hypoglycemic and hypolipidemic activities.
AB  - New arylidene-thiazolidinediones (ATZDs) were synthesized and evaluated in the
      alloxan-induced hyperglycemia mice model. The molecular target taken into
      consideration is the nuclear PPAR-gamma whose crystallographic structure is
      available on the PDB database as 2PRG. Thus the hypoglycemic and hypolipidemic
      activities of compounds were compared with the result of their docking after
      removal of the co-crystallized ligand present in the 2PRG structure. Molecular
      modeling studies were carried out using the Autodock 3.0.5 and ADT 1.1 programs.

PMID- 17448574
TI  - 1-Aryl-4,6-dihydropyrazolo[4,3-d][1]benzazepin-5(1H)-ones: a new class of
      antiproliferative agents with selectivity for human leukemia and breast cancer
      cell lines.
AB  - The synthesis of 1-aryl-4,6-dihydropyrazolo[4,3-d][1]benzazepin-5(1H)-ones by
      cyclization of 4-[(dimethylamino)methylidene]-3,4-dihydro-1H-[1]benzazepine-2,5
      dione with arylhydrazines is reported. When tested on a panel of human cancer
      cell lines, the title compounds showed antiproliferative activity and a
      characteristic selectivity pattern of growth inhibition. Although structurally
      akin to established kinase inhibitors, the new compounds did not exhibit
      noteworthy inhibitory activity when tested on an array of cancer-related kinases.

PMID- 17448575
TI  - Antileukotrienic N-arylethyl-2-arylacetamides in the treatment of ulcerative
      colitis.
AB  - A series of arylacetic acid derivatives bearing methyl(arylethyl)amino groups
      were prepared and their antileukotrienic activities involving LTB(4) were
      evaluated. Regression analysis has shown a strong dependence of these activities
      on lipophilicity for both LTB(4) receptor binding and inhibition of LTB(4)
      biosynthesis; parabolic relationships were derived. The values of slopes of the
      ascending linear parts of these dependences indicate various types of hydrophobic
      binding at the site of ligand interaction with relevant biomacromolecules. The
      anti-inflammatory effect of the compounds under study was also evaluated in three
      animal models of inflammation and their possible utilization in the treatment of
      ulcerative colitis (UC) was followed. The importance of antileukotrienic
      activities for the anti-inflammatory effect, especially in the model of UC was
      discussed, but further experiments are necessary to confirm the respective
      relations.

PMID- 17448576
TI  - Insights into the structural requirements of farnesyltransferase inhibitors as
      potential anti-tumor agents based on 3D-QSAR CoMFA and CoMSIA models.
AB  - A three-dimensional quantitative structure-activity relationship (3D-QSAR) study
      was performed on three different chemical series reported as selective
      farnesyltransferase (FTase) inhibitors employing comparative molecular field
      analysis (CoMFA) and comparative molecular similarity indices (CoMSIA) techniques
      to investigate the structural requirements for substrates and derive a predictive
      model that may be used for the design of novel FTase inhibitors. Removal of
      outliers improved the predictive power of models developed for all three
      structurally diverse classes of compounds. 3D-QSAR models were derived for 3
      aminopyrrolidinone derivatives (training set N=38, test set N=7), 2-amino
      nicotinonitriles (training set N=46, test set N=13) and 1-aryl-1'-imidazolyl
      methyl ethers (training set N=35, test set N=5). The CoMFA models with steric and
      electrostatic fields exhibited r(2)(cv) 0.479-0.803, r(2)(ncv) 0.945-0.993,
      r(2)(pred) 0.686-0.811. The CoMSIA models displayed r(2)(cv) 0.411-0.814,
      r(2)(ncv) 0.923-0.984, r(2)(pred) 0.399-0.787. 3D contour maps generated from
      these models were analyzed individually, which provide the regions in space where
      interactive fields may influence the activity. The superimposition of contour
      maps on the active site of farnesyltransferase additionally helps in
      understanding the structural requirements of these inhibitors. 3D-QSAR models
      developed may guide our efforts in designing and predicting the FTase inhibitory
      activity of novel molecules.

PMID- 17448577
TI  - Anaphylaxis: case definition and guidelines for data collection, analysis, and
      presentation of immunization safety data.

PMID- 17448578
TI  - Randomised, double-blind, safety and efficacy of a killed oral vaccine for
      enterotoxigenic E. Coli diarrhoea of travellers to Guatemala and Mexico.
AB  - We tested the efficacy of a killed oral vaccine for enterotoxigenic Escherichia
      coli (ETEC) diarrhoea to determine if two doses of vaccine with colonization
      factor antigens (CF) and cholera B subunit would protect against ETEC diarrhoea
      of travellers. Six hundred seventy-two healthy travellers going to Mexico or
      Guatemala were studied in a prospective, randomised, placebo-controlled trial.
      The primary outcome was a vaccine preventable outcome (VPO), defined as an
      episode of ETEC diarrhoea with an ETEC organism producing heat labile toxin (LT)
      or CF homologous with the vaccine, without other known causes. The vaccine was
      safe and stimulated anti-heat labile toxin antibodies. There was a significant
      decrease in more severe VPO episodes (PE=77%, p=0.039) as defined by symptoms
      that interfered with daily activities or more than five loose stools in a day,
      although the total number of VPO events did not differ significantly in the
      vaccine and placebo groups. We conclude that the new oral ETEC vaccine reduces
      the rate of more severe episodes of traveller's diarrhoea (TD) due to VPO-ETEC,
      but it did not reduce the overall rate of ETEC diarrhoea or of travellers'
      diarrhoea due to other causes.

PMID- 17448580
TI  - A social comparison theory analysis of group composition and efficacy of cancer
      support group programs.
AB  - Group-based psychosocial programs provide an effective forum for improving mood
      and social support for cancer patients. Because some studies show more benefit
      for patients with initially high psychosocial distress, and little or no benefit
      for patients with initially low distress, support programs may better address
      patient needs by only including distressed patients. However, distressed patients
      may benefit particularly from the presence of nondistressed patients who model
      effective coping, an idea many researchers and extensions of social comparison
      theory support. We present a theoretical analysis, based on a social comparison
      perspective, of how group composition (heterogeneous group of distressed and
      nondistressed patients versus homogeneous group of distressed patients) may
      affect the efficacy of cancer support programs. We propose that a heterogeneous
      group allows distressed patients maximal opportunity for the various social
      comparison activities they are likely to prefer; a homogeneous group does not.
      Though the presence of nondistressed patients in a heterogeneous group
      potentially benefits distressed patients, the benefits for nondistressed patients
      are unclear. For nondistressed patients, heterogeneous groups may provide limited
      opportunities for preferred social comparison activity and may create the
      possibility for no benefit or even negative effects on quality of life. We also
      discuss ethical issues with enrolling nondistressed patients whose presence may
      help others, but whose likelihood of personal benefit is questionable.

PMID- 17448581
TI  - Creating a place for population health: interpreting the spaces of a new School
      in Auckland, New Zealand.
AB  - Although the reconfiguring of health care within the hospital sector has gained
      considerable attention by social scientists, the tertiary education sector's
      response to new health philosophies and practices has proceeded largely
      unexamined. This paper considers the new School of Population Health at the
      University of Auckland, accounts for its origins and considers the synergies
      between its design and workplace organisation. The results of a thematic analysis
      of narratives offered by 24 employees collected in 2004 are then presented.
      Findings suggest that the amassing of academics from a range of health-related
      backgrounds is advancing interdisciplinary dialogue even if the nature and
      purpose of population health remains unclear to some. A key concern of
      respondents was the openness of the workplace which encourages a collaborative
      atmosphere but also generates distraction. The degree to which conduct within the
      new building is perceived as regulated was also of concern. Place clearly matters
      in the story of the new School: the form of the building (featuring an
      architecture of openness) complements its function (generating new collaborations
      and creative thinking about health). However, the question of how 'salutogenic' a
      setting it is remains contested.

PMID- 17448579
TI  - Risk for recurrence in depression.
AB  - Depression is a highly recurrent disorder with significant personal and public
      health consequences. Prevention of recurrence would be extremely desirable, and
      thus researchers have begun to identify risk factors that are specific to
      recurrence, which may be different from risk factors for first onset of
      depression. Methodological issues in this area of research are briefly reviewed
      (e.g., the various definitions of "recurrence" and "depression"), followed by a
      review of studies on specific risk factors, including demographic variables
      (gender, socio-economic status, and marital status), clinical variables (age at
      first onset, number of prior episodes, severity of first/index episode, and
      comorbid psychopathology), family history of psychopathology, and psychosocial
      and psychological variables (level of psychosocial functioning, cognitions,
      personality, social support, and stressful life events). In addition, scar
      theories are evaluated for their potential to explain how these variables and
      recurrent depression are linked. Our review suggests that recurrent depression
      reflects an underlying vulnerability that is largely genetic in nature and that
      may predispose those high in the vulnerability not only to recurrent depressive
      episodes, but also to the significant psychosocial risk factors that often
      accompany recurrent depression.

PMID- 17448582
TI  - Secrets and lies: Breastfeeding and professional paid work.
AB  - This paper explores the conflict between health advice and organisational
      practice regarding breastfeeding. It focuses on the group of mothers with the
      highest rates of both breastfeeding initiation and of continuous employment
      following maternity leave: specifically, educated mothers in managerial and/or
      professional occupations. In this context, the paper investigates, through in
      depth interviews, the embodied experiences of 20 heterosexual UK mothers,
      qualified to degree level, who returned to professional employment within 1 year
      of childbirth. The paper observes that mothers who attempted to combine
      breastfeeding with paid work did so with difficulty because the material activity
      of breastfeeding was 'taboo' within the workplace. Thus, the requirement to
      conform to organisational expectations regarding 'suitable' embodied behaviour
      contradicted health advice about what was 'best' for infant children. In order to
      comply with workplace requirements, mothers in the study were obliged either to
      cease breastfeeding or to conceal breastfeeding activities. In the light of
      mothers' experiences, the paper suggests that breastfeeding duration rates among
      professionally employed mothers can only be improved if negative attitudes about
      maternal bodies and employment are challenged and if employers, as well as
      mothers, are the focus of health initiatives aimed at promoting breastfeeding.

PMID- 17448583
TI  - Explanations of depression among Irish migrants in Britain.
AB  - Irish geographical and cultural propinquity to the UK might be considered as an
      advantage to migrants. However, research over 40 years shows Irish migrants to
      have consistent high vulnerability to mental disorders. Only recently have
      researchers begun to explore the reasons for this morbidity. Taking a previous
      epidemiological study on depression and Irish migrants as a point of departure,
      we explored the reasons for this morbidity--we hypothesised that depression may
      be related to unprepared or spontaneous migration. We report on a qualitative
      study in order to clarify how, from the migrant's perspective, migration might be
      related to depression. These perspectives were obtained through in-depth
      interviews with Irish-born migrants aged 18 and over living in London in order to
      explore psychological distress through a contextualised 'insiders' account. The
      interviews were completed with men and women who experienced depression and
      others who had not. We found that previous theories on Irish migrant psychiatric
      disorder such as racial discrimination were not supported by the narratives of
      Irish migrant experience. For many participants, the origins of distress are
      located in Ireland or in difficult life events and circumstances without a direct
      relationship to migration. This paper examines the causal attributes to
      depression among Irish migrants in the UK in the context of pre- and post
      migration experiences with particular focus on gender and age.

PMID- 17448584
TI  - Differences in acute toxicity syndromes of 2,3,7,8-tetrachlorodibenzo-p-dioxin
      and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin in rats.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of
      polychlorinated dibenzo-p-dioxins. The potency of 1,2,3,4,7,8-hexachlorodibenzo-p
      dioxin (HxCDD) is only 10% of that of TCDD for typical aryl hydrocarbon receptor
      (AHR)-mediated effects. Acute lethality, macroscopic effects, and liver toxicity
      of TCDD and HxCDD were compared in male rats of the strain Han/Wistar (Kuopio;
      H/W), and of the lines A and B. The latter two rat lines originate from
      crossbreeding of H/W and Long-Evans (Turku/AB) rats. H/W and line A rats are
      highly resistant to acute toxicity of TCDD due to an altered AHR, while line B
      rats are moderately resistant due to H/W-type alleles of another, yet
      unidentified gene contributing to TCDD resistance ("gene B"). The rats received
      200-10,000 microg/kg of either TCDD or HxCDD intragastrically and were monitored
      for 46 days. In all rats, the highest dose of HxCDD (10,000 microg/kg) reduced
      body weight more effectively than an identical dose of TCDD. Only HxCDD (10,000
      microg/kg) caused gastrointestinal hemorrhage, pale (fatty) livers and death by
      day 15 in H/W and line A rats. In line B rats, HxCDD caused pronounced hepatic
      fatty degeneration, whereas TCDD induced hepatic accumulation of biliverdin and
      its derivatives. Both congeners induced sinusoidal distension in liver. In H/W
      and line A rats, the estimated LD(50) values were >10,000 microg/kg and 2000
      10,000 microg/kg for TCDD and HxCDD, respectively; for line B rats they were 480
      microg/kg and 1000-2000 microg/kg, respectively. Thus, HxCDD was more potent than
      TCDD in inducing acute mortality in H/W and line A rats, contrary to what is
      predicted by toxic equivalency factor (TEF) values. In line B, the expected rank
      order of potencies prevailed. These findings suggest that in addition to the
      canonical AHR-mediated toxic pathways, HxCDD possesses an AHR-independent
      mechanism of toxicity, whose main manifestations are rapid body weight loss,
      mortality, fatty liver and gastrointestinal hemorrhage.

PMID- 17448585
TI  - Protective role of selenium against renal toxicity induced by cadmium in rats.
AB  - Cadmium is an environmental toxic metal implicated in human diseases. The
      mechanism of its toxicity is not fully understood. Therefore, the role of cadmium
      in renal toxicity, and the protective role of selenium against this toxicity were
      investigated. Forty-five male rats were used through out the study and divided
      into three groups of 15. The first group received saline solution daily for 10
      days. The second group, received cadmium chloride (CdCl2) (2 mg/kg body weight)
      intraperitoneally daily for a period of 10 days. The third group, received sodium
      selenite (1 mg/kg body weight, twice in 10 days) and cadmium chloride (CdCl2)
      once a day [corrected] The results showed that cadmium treatment increased renal
      lipid peroxidation (measured as malondialdehyde, MDA) which was associated with a
      significant decrease in the antioxidant systems such as reduced glutathione
      levels and the activities of glutathione peroxidase (GPx) and thioredoxin
      reductase (TrxR). On the other hand, pretreatment of rats with selenium and
      cadmium led to a significant decrease in MDA concentration, and increased levels
      of GSH and the activities of GPx and TrxR when compared with those of cadmium
      treated group. The total levels of phospholipid, triglyceride, and
      cholesterolester classes were decreased, while free fatty acids levels were
      markedly increased after cadmium treatment. In addition, the total levels of both
      mono- and poly-unsaturated fatty acids of different lipid classes were
      significantly decreased, while the total saturated fatty acids was significantly
      increased by cadmium treatment. Pretreatment of rats with selenium, was found to
      protect kidney tissues of rats against the biochemical changes resulting from
      cadmium administration. These results suggest that cadmium causes renal toxicity
      by inducing lipid peroxidation, decreasing antioxidant systems, and also by
      altering lipid metabolism. In addition, selenium treatment could protect the
      kidney tissues against the toxicity of cadmium since it reduced MDA levels and
      increased the activities of antioxidant enzymes in these tissues. These results
      could be important for the further understanding of the complex mechanisms of
      cadmium toxicity in kidney tissues and in the development of better treatments
      for people and/or animals exposed to the heavy metal.

PMID- 17448586
TI  - Formulation-dependent toxicokinetics explains differences in the GI absorption,
      bioavailability and acute neurotoxicity of deltamethrin in rats.
AB  - The acute neurotoxicity of pyrethroid insecticides varies markedly with the
      dosage vehicle employed. The objective of the present study was to assess the
      influence of two common vehicles on the bioavailability and toxicokinetics (TK)
      of a representative pyrethroid insecticide, deltamethrin (DLM), to determine
      whether the vehicles influence toxic potency by modifying the chemical's TK.
      Adult, male Sprague-Dawley rats were administered DLM iv or po, either by
      dissolving it in glycerol formal (GF) or by suspending it in Alkamuls (AL).
      Groups of rats received 10mg DLM/kg by gavage in each vehicle, as well as 2 mg/kg
      in GF or 10mg/kg in AL by iv injection. Serial blood samples were collected over
      96 h and analyzed for their DLM content by HPLC. In a second experiment, plasma,
      brain, fat, liver and lung DLM concentrations were measured 2h after giving 10mg
      DLM/kg orally in GF or AL. In a third experiment rats received 2 or 10mg DLM/kg
      iv in AL or 2mg DLM/kg iv in GF. Lung DLM content was determined 15 min post
      injection. DLM particle size in both formulations was measured under a phase
      contrast microscope. DLM appeared to be completely dissolved in GF, while
      particle size ranged from <5 to >50 microm in AL. The bioavailability of DLM in
      the aqueous AL suspension was approximately 9-fold lower than in GF (1.7% versus
      15%). Blood C(max) (0.95+/-0.27 versus 0.09+/-0.01 microg/ml) and AUC(0)(48h)
      (5.49+/-0.22 versus 0.61+/-0.14 microg.h/ml) were markedly higher in the GF
      gavage group. Tissue DLM levels were also significantly higher in the GF animals
      at 2h. The 10mg/kg po and 2mg/kg iv doses of DLM in GF produced moderate
      salivation and slight tremors. Rats receiving the insecticide in AL were
      asymptomatic. IV injection of the AL suspension resulted in trapping of much of
      the dose in the pulmonary capillaries. As anticipated, the injected suspension
      had a longer half-life and slower clearance than did the GF formulation. In
      summary, limited dissolution of the highly lipophilic DLM particles in the AL
      suspension severely limited DLM's GI absorption, bioavailability, target organ
      deposition and acute neurotoxic potency.

PMID- 17448587
TI  - Revisiting the astrocyte-oligodendrocyte relationship in the adult CNS.
AB  - The lineages of both astrocytes and oligodendrocytes have been popular areas of
      research in the last decade. The source of these cells in the mature CNS is
      relevant to the study of the cellular response to CNS injury. A significant
      amount of evidence exists to suggest that resident precursor cells proliferate
      and differentiate into mature glial cells that facilitate tissue repair and
      recovery. Additionally, the re-entry of mature astrocytes into the cell cycle can
      also contribute to the pool of new astrocytes that are observed following CNS
      injury. In order to better understand the glial response to injury in the adult
      CNS we must revisit the astrocyte-oligodendrocyte relationship. Specifically, we
      argue that there is a common glial precursor cell from which astrocytes and
      oligodendrocytes differentiate and that the microenvironment surrounding the
      injury determines the fate of the stimulated precursor cell. Ideally, better
      understanding the origin of new glial cells in the injured CNS will facilitate
      the development of therapeutics targeted to alter the glial response in a
      beneficial way.

PMID- 17448588
TI  - Quantitative echography in the follow-up of patients treated with proton-beam
      irradiation for primary choroidal melanomas.
AB  - Quantitative ultrasonic characterization yields information that is correlated to
      the tissue microstructure and increases the diagnostic potential of ultrasound.
      The measurement of acoustic properties of melanomas in vivo has not yet been
      reported after proton-beam irradiation. This prospective study was conducted on a
      cohort of 50 patients diagnosed with primary malignant melanoma to assess in vivo
      the ability of quantitative echography to detect changes in choroidal malignant
      melanomas after proton-beam irradiation and to follow the ultrasonographic
      changes during 24 months posttreatment. Echographic evaluations of these patients
      were performed at diagnosis and repeated every 6 months after treatment over a 2
      y period. The acoustic parameters included in this work are derived from the
      calibrated tissue backscatter spectra (spectral slope, spectral intercept and
      apparent integrated backscatter) of a selected tumor volume after correction of
      the apparatus transfer function and beam diffraction. Clinical parameters
      resulting from conventional echography were also quantified and included mainly
      tumor height, tumor vascularity and internal reflectivity. Spectral intercept and
      apparent integrated backscatter were found to be the most useful to evaluate
      changes in melanomas after treatment. Significant (p < 0.05) differences of these
      parameter values were observed between pre- and postproton therapy. In
      particular, significant changes (compared with baseline) were observed for these
      parameters, even when the tumor size after treatment was not significantly
      different from baseline. The results suggest that quantitative spectrum analysis
      of frequency-dependent backscatter can provide information about the structural
      modifications of choroidal malignant melanomas as a result of proton-beam
      irradiation.

PMID- 17448589
TI  - Measurement of the reflectivity of the intima-medial layer of the common carotid
      artery improves the discriminatory value of intima-medial thickness measurement
      as a predictor of risk of atherosclerotic disease.
AB  - Our aim was to assess the predictive value of a measurement of intima-medial
      layer (IML) reflectivity in the differentiation of pathological from
      physiological increases in intima-medial thickness (IMT). Both common carotid
      arteries (CCA) of familial hypercholesterolemia (FH) patients and age- and sex
      matched controls (no cardiovascular risk factors) were imaged using a 10- to 15
      MHz linear array transducer (n = 30). Images of the CCA far wall were analyzed in
      the IMT "plug-in" of "HDI Lab." The IML reflectivity, averaged over an 8- to 12
      mm length of arterial wall, was expressed as a ratio of reflectivity at a point
      0.21-mm deep to the intima-medial interface divided by the reflectivity at the
      intima-medial interface, termed the intima-medial reflectivity index (IMRI). The
      risk of atherosclerosis was assessed in terms of IMT alone and IMT coupled with
      IMRI. Defining high risk of atherosclerosis in FH, in terms of both IMT alone and
      IMT coupled with IMRI, produced an appropriate, when compared with cholesterol
      years score, statistically significant stratification (p < 0.01 and p < 0.005).
      Analysis of the low-risk subjects revealed a tendency to define a subject as
      "high risk" based on a physiological increase in IMT, but when IMRI is included
      in the assessment, all controls are correctly identified as low risk. This method
      of quantifying the reflectivity of the IML improved the discriminatory
      performance of IMT increase as an indicator of atherosclerotic risk by enabling a
      smaller, therefore earlier, increase in IMT to be considered pathologic when
      accompanied by an increase in IMRI.

PMID- 17448590
TI  - Application of the magnitude-squared coherence function between uterine and
      umbilical flow velocity waveforms for predicting placental dysfunction: a
      preliminary study.
AB  - To examine whether the magnitude-squared coherence between uterine and umbilical
      blood flow velocity waveforms can, in conjunction with estimated fetal weight,
      uterine and umbilical pulsatility indices, fetal and maternal heart rates,
      diastolic notching and the amniotic fluid index, create a sensitive and specific
      model for the prediction of placental dysfunction. Binary logistic prediction
      models are created for preeclampsia, pregnancy induced hypertension and
      intrauterine growth restriction in a study group of 284 unselected midtrimester
      pregnancies. In each study group, the median value of derived parameters were
      compared with the uncomplicated pregnancy control group. The magnitude-squared
      coherence function between the uterine and umbilical flow velocity waveforms was
      found to be a statistically significant predictor of preeclampsia during the
      midtrimester of pregnancy. The magnitude-squared coherence did not improve the
      prediction of intrauterine growth restriction or pregnancy induced hypertension.
      The inclusion of magnitude-squared coherence as one of the prediction parameters
      may improve the early identification of pregnancies subsequently complicated by
      preeclampsia.

PMID- 17448591
TI  - Editorial comment on: Low-activity V89L variant in SRD5A2 is associated with
      aggressive prostate cancer risk: an explanation for the adverse effects observed
      in chemoprevention trials using 5-alpha-reductase inhibitors.

PMID- 17448592
TI  - Anatomical extent of pelvic lymphadenectomy in patients undergoing radical
      prostatectomy.
AB  - OBJECTIVES: The rationale for locoregional staging lymphadenectomy in prostate
      cancer (pCA) lies in the accurate diagnosis of occult micrometastases to stratify
      patients who might benefit from adjuvant therapeutic measures. In pCA, the issues
      of the necessity and the therapeutic advantage of pelvic lymphadenectomy (PLND])
      in patients with low-, intermediate-, and high-risk disease are still discussed
      controversially. The aim of this review manuscript is to critically evaluate the
      current status on PLND in pCA. METHODS: A review of the literature was performed
      concerning radical prostatectomy and PLND with respect to anatomical extent,
      oncological outcome, and associated complications. RESULTS: The anatomical
      lymphatic drainage of the prostate includes the obturator fossa, and the external
      and internal iliac arteries; therefore, at least these areas should be included
      in PLND. According to the current clinical studies, extended PLND (ePLND)
      significantly increases the yield of both total lymph nodes and lymph node
      metastases independent of the risk classification of pCA. Lymph node metastases
      will be detected in about 5-6%, 20-25%, and 30-40% of low-, intermediate-, and
      high-risk pCA, respectively. Exclusively 25% of all positive lymph nodes are
      located in the area around the internal iliac artery. With regard to progression
      free and cancer-specific survival, retrospective analysis of the SEER data and
      additional case-control studies indicate a direct positive relationship between
      the number of removed lymph nodes and long-term oncological outcome in patients
      with limited lymph node involvement or negative lymph nodes. In these patients,
      cancer-specific survival is improved by about 15-20%. On the basis of results of
      large case-control studies, complication rates of ePLND are not significantly
      increased. CONCLUSIONS: On the basis of current data, the following conclusions
      can be drawn: (1) If performed, PLND has to be done in the extended, anatomically
      adequate variant. (2) The frequency of lymph node metastases in low-risk pCA is
      low, and the issue of PLND has to be discussed with the patient. (3) If radical
      prostatectomy is performed in intermediate- and high-risk pCA, an ePLND should be
      option of choice. For the future, ongoing prospective trials have to demonstrate
      a benefit in terms of biochemical-free and cancer-specific survival.

PMID- 17448593
TI  - Low-activity V89L variant in SRD5A2 is associated with aggressive prostate cancer
      risk: an explanation for the adverse effects observed in chemoprevention trials
      using 5-alpha-reductase inhibitors.
AB  - OBJECTIVE: The 5-alpha-reductase type 2 (5A2) enzyme catalyses the irreversible
      conversion of testosterone to dihydrotestosterone, the most active androgen in
      the prostate. This key enzyme in prostate gland physiopathology has recently been
      targeted by using inhibitors for chemoprevention of prostate cancer. However,
      some controversies have arisen by the observation of greater than expected high
      grade tumours in men diagnosed with prostate cancer in the finasteride
      chemoprevention trial. To help understand the impact of prolonged exposure to low
      5A2 activity on prostate cancer risk, we analysed the rather common genetic V89L
      polymorphism, which has previously been well characterised functionally for
      determining low enzymatic activities. METHODS: The study was performed on 1605
      white Caucasian French men categorised in 803 patients with prostate
      adenocarcinoma and 802 matched healthy male controls. The different alleles and
      genotypes were analysed according to case-control status and the aggressiveness
      pattern of the tumours. RESULTS: The V89L amino acid substitution leading to the
      homozygous genotype LL increased the risk of clinically significant disease (odds
      ratio [OR]=1.89, 95% confidence interval (%95 CI), 1.07-2.74; p=0.0017) and was
      also associated with the most aggressive patterns of the disease (OR=2.56, 95%CI,
      1.41-4.63; p=0.002). CONCLUSIONS: Our data confirm in a large and homogeneous
      Caucasian French population that the low-activity V89L variant is associated with
      an increased risk of aggressive prostate cancer. These results corroborate that
      long-term exposure to 5A2 inhibitors (chemoprevention) must be evaluated in terms
      of risk of prostate cancer adverse effects.

PMID- 17448594
TI  - Editorial comment on: Low-activity V89L variant in SRD5A2 is associated with
      aggressive prostate cancer risk: an explanation for the adverse effects observed
      in chemoprevention trials using 5-alpha-reductase inhibitors.

PMID- 17448595
TI  - Editorial comment on: marked gene transcript level alterations occur early during
      radical prostatectomy.

PMID- 17448596
TI  - Editorial comment on: marked gene transcript level alterations occur early during
      radical prostatectomy.

PMID- 17448597
TI  - Marked gene transcript level alterations occur early during radical
      prostatectomy.
AB  - OBJECTIVES: Gene expression analyses have become an important approach to
      understand the biology of cancer. However, transcript level patterns and RNA
      quality could rapidly change in response to ischemic and mechanical stress.
      Studies have shown that this occurs both perioperatively and after surgical
      removal of organs. METHODS: To better understand the relative importance of
      perioperative and postoperative gene expression changes, we performed
      quantitative reverse transcription-polymerase chain reactions on the transcripts
      of 91 cancer-related genes from normal and cancerous prostate tissues from 10
      patients at eight different time points during surgical manipulation and after
      removal of the prostate. RESULTS: The mRNA levels of 8 (EGR1, p21, KRT17, PIM1,
      S100P, TNFRSF, WFDC2, and TRIM29) of 91 genes changed significantly with time of
      surgery in normal and tumor tissue. Remarkably, all eight genes were up
      regulated, a reaction that was most prominent during the early intraoperative
      period. Additional changes occurred but were much less prominent during the first
      postoperative hour. CONCLUSIONS: Our results substantially challenge the utility
      of immediate postoperative tissue sampling. At least for prostate cancer, the
      data suggest that preoperative tissue collection by core biopsies is optimal for
      studying molecular changes in normal and neoplastic prostate tissues.

PMID- 17448598
TI  - Curcumin for chemoprevention of colon cancer.
AB  - The most practical approach to reduce the morbidity and mortality of cancer is to
      delay the process of carcinogenesis through the use of chemopreventive agents.
      This necessitates that safer compounds, especially those derived from natural
      sources must be critically examined for chemoprevention. A spice common to India
      and the surrounding regions, is turmeric, derived from the rhizome of Curcuma
      longa. Pre-clinical studies in a variety of cancer cell lines including breast,
      cervical, colon, gastric, hepatic, leukemia, oral epithelial, ovarian,
      pancreatic, and prostate have consistently shown that curcumin possesses anti
      cancer activity in vitro and in pre-clinical animal models. The robust activity
      of curcumin in colorectal cancer has led to five phase I clinical trials being
      completed showing the safety and tolerability of curcumin in colorectal cancer
      patients. To date clinical trials have not identified a maximum tolerated dose of
      curcumin in humans with clinical trials using doses up to 8000mg per day. The
      success of these trials has led to the development of phase II trials that are
      currently enrolling patients. Overwhelming in vitro evidence and completed
      clinical trials suggests that curcumin may prove to be useful for the
      chemoprevention of colon cancer in humans. This review will focus on describing
      the pre-clinical and clinical evidence of curcumin as a chemopreventive compound
      in colorectal cancer.

PMID- 17448599
TI  - An evaluation of stability by thermogravimetric analysis of digestate obtained
      from different biowastes.
AB  - Research was carried out with the aim of monitoring anaerobic digestion processes
      using thermal analysis with the aid of mass spectrometry so as to define the
      stability of the digestate obtained. Three different systems were investigated
      under varying conditions. The digestion of waste sludge from a pharmaceutical
      industry (PI) and the digestion of cattle manure (CM) were evaluated under
      mesophilic conditions. The co-digestion of a mixture of primary sludge (PS) and
      the organic fraction of municipal solid wastes (OFMSW) was studied under
      thermophilic conditions. Temperature-programmed combustion tests were carried out
      to investigate the degree of stabilization of samples throughout the digestion
      processes. The derivative thermogravimetry (DTG) profiles obtained for the
      mesophilic digestion of PI waste showed a decrease at low temperatures and an
      increase at high temperatures in the intensity of the peaks recorded as the
      stabilization process proceeded. These results are in accordance with those
      obtained by the present authors in their previous work on the mesophilic
      digestion of primary sludge and OFMSW. In contrast, the DTG profiles obtained
      from the stabilization process of CM and thermophilic codigestion of PS and OFMSW
      showed a reduction in peaks at high temperatures. When the stabilization products
      obtained from CM by anaerobic digestion and by composting processes were
      compared, it was observed that the composting process was capable of further
      decomposing materials readily oxidized at low temperatures and increasing the
      presence of structurally more complex substances. The evolution of the
      differential thermal analysis (DTA) signal recorded simultaneously showed
      considerable similarity to the mass/charge (m/z) signal 44 registered by the mass
      spectrometer. The use of mass spectrometry helped to clarify the inner workings
      of the digestion process.

PMID- 17448600
TI  - Electron beam-induced thickening of the protective oxide layer around Fe
      nanoparticles.
AB  - There are many circumstances in science where the process of measuring the
      properties of a system alters the system. An imaging process can exert an
      inadvertent effect on the object being observed. Consequently, what we observe
      does not necessarily represent what had been present before the observation.
      Normally, this effect can be ignored if the consequence of such a change is
      believed not to be significant. The expansion of nanostructured materials has
      made high-resolution transmission electron microscopy one of the indispensable
      tools for probing the characteristics of nanomaterials. Modification of
      nanoparticles by the electron beam during their imaging has been widely noticed
      and this is generally believed to be due to electron beam-induced heating effect,
      defect formation in the particles, charging of the particle, or excitation of
      surrounding gases. However, an explicit experimental identification of which
      process dominates is often very hard to establish. We report the thickening of
      native oxide layer on iron nanoparticle under electron beam irradiation. Based on
      atomic level imaging, electron diffraction, and computer simulation, we have
      direct evidence that the protecting oxide layer formed on Fe nanoparticle at room
      temperature in air or oxygen continues to grow during an electron beam
      bombardment in the vacuum system typical of most TEM systems. Typically, the
      oxide layer increases from approximately 3 to approximately 6 nm following
      approximately 1h electron beam exposure typically with an electron flux of 7 x
      10(5)nm(-2)s(-1) and an vacuum of approximately 3 x 10(-5)Pa. Partial
      illumination of a nanoparticle and observation of the shell thickening
      conclusively demonstrates that many of the mechanisms postulated to explain such
      processes are not occurring to a significant extent. The observed growth is not
      related to the electron beam-induced heating of the nanoparticle, or residual
      oxygen ionization, or establishment of an electrical field, rather it is related
      to electron beam-facilitated mass transport across the oxide layer (a defect
      related process). The growth follows a parabolic growth law.

PMID- 17448601
TI  - Summary of the Atom Probe Tomography Workshop IFES 2006 July 18, 2006 Guilin,
      China.

PMID- 17448602
TI  - First finding of libyostrongylosis in farm-reared ostriches (Struthio camelus) in
      Croatia: unusual histopathological finding in the brain of two ostriches,
      naturally infected with Libyostrongylus douglasi.
AB  - In the present work, the very first finding of Libyostrongylus douglasi in farm
      reared ostriches in Croatia, was described, not only as the main cause of the
      death, but also as the cause of persistent infection. The results of
      histopathological examination of almost all parenchymatous organs in two
      routinely necropsied ostriches were presented, including atypical
      histopathological finding in the brain and the result of the L. douglasi scanning
      electron microscopical (SEM) examination. In order to determine the parasite
      species to which the larval form found in the brain belonged, polymerase chain
      reaction (PCR) was performed. Total DNA was isolated from fresh L. douglasi, and
      from archival formalin-fixed and paraffin-embedded brain section. Additionally,
      the smears of the proventricular mucosal lining were cytologically examined.
      Virological examination for newcastle disease virus (NDV) was also performed. As
      there was very limited information concerned ostrich's health status in Croatian
      farms, a preliminary evaluation of the parasite infestation level in the Croatian
      ostrich population over the period 2001-2002 was also done, and an attempt at
      characterising individual parasite species, was made.

PMID- 17448603
TI  - Evaluation of strongyloidiasis in kennel dogs and keepers by parasitological and
      serological assays.
AB  - Strongyloides stercoralis is an intestinal nematode with worldwide distribution,
      particularly in tropical and subtropical regions. Due to the low sensitivity of
      traditional parasitological methods, the detection of serum specific antibodies
      may serve as an alternative test for the diagnosis. The aims of the present study
      were to verify the occurrence of S. stercoralis and the presence of specific IgG
      antibodies to the parasite in kennel dogs and keepers, using parasitological and
      serological assays. A total of 181 dogs were examined from 7 breeding kennels in
      the city of Uberlandia, southeastern region of Brazil and distributed as follows:
      kennel A (n=41), kennel B (n=16), kennel C (n=11), kennel D (n=63), kennel E
      (n=11), kennel F (n=18) and kennel G (n=21). Fecal and serum samples from 11
      keepers responsible for kennel cleaning and dog control were also collected in
      five of the seven kennels (two from kennel A, one from kennel B, four from kennel
      D, two from kennel E and two from kennel G). Overall, enteroparasites were
      detected by parasitological assays in 66, 36.5% (95% CI: 2.5-43.4%) of the 181
      dogs tested. Only one (0.6%) dog was copropositive for S. stercoralis. Among the
      keepers only one fecal sample, 9.1% (95% CI: 8.6-9.4%) was positive for hookworm
      by the Lutz method. Serological assays showed that 44 (24.3%) of the 181 dogs
      were seropositive for S. stercoralis in at least one of the tests in the
      following kennels: 21 (11.6%) in kennel A; 1 (0.6%) in kennel B; 5 (2.7%) in
      kennel C; 6 (3.3%) in kennel D; 1 (0.6%) in kennel E; 9 (4.9%) in kennel F and 1
      (0.6%) in kennel G. Among the keepers no S. stercoralis seropositive samples were
      identified using IFAT but 2 (18.2%) of the keepers from kennel D and 1 (9.1%)
      from kennel G were seropositive by ELISA. The present study demonstrated that the
      occurrence of S. stercoralis infection in kennel dogs and keepers is low in the
      city of Uberlandia and that serological assays can contribute to the diagnosis of
      canine as well as human strongyloidiasis.

PMID- 17448604
TI  - Progress in the epidemiology and diagnosis of amitraz resistance in the cattle
      tick Boophilus microplus.
AB  - Amitraz is a rapidly acting acaricide that has been in use for the control of
      cattle ticks for more than 30 years. Resistance against amitraz was first
      reported in Boophilus microplus in Australia in 1980 but has been slow to spread
      in comparison to resistance against synthetic pyrethroids. The most recent
      estimate of prevalence of amitraz resistance in Australia is 10.8%. In Mexico,
      the development and distribution of amitraz appears to have been more rapid and
      the prevalence has been estimated to be 19.4% in Yucatan state. In New Caledonia,
      about 10% of properties were confirmed to have amitraz resistance. There is
      little reliable information on the prevalence of amitraz resistance in southern
      Africa. Risk factors have been identified, but the small sample sizes in the
      studies that have attempted to identify risk factors using survey data suggest
      caution in their interpretation. Regional variation in prevalence has been
      reported, as has a positive relationship with frequency of acaricide application.
      There is evidence to suggest that in Australia, amitraz resistance might have
      emerged on a small number of properties and been disseminated by cattle
      movements. There is also some evidence to suggest that amitraz resistance can
      diminish in the field when selection pressure is not applied. The mode of
      inheritance of amitraz resistance is uncertain and it has been suggested that it
      is a polygenic trait. The mechanism of amitraz resistance is unknown. Two
      possibilities have been proposed: octopamine receptor and monoamine oxidase.
      There is some equivocal support for both possibilities. The larval packet test
      bioassay is the most reliable method of diagnosing amitraz resistance in B.
      microplus, and this test has been modified by Miller to provide more accuracy and
      repeatability. Molecular tests are in development but will not eliminate the need
      for the bioassay.

PMID- 17448605
TI  - Temporal modeling demonstrates preserved overlearning processes in schizophrenia:
      an fMRI study.
AB  - Working memory (WM) deficits are a core feature of schizophrenia. However, it has
      not been examined whether these deficits are related to altered temporal dynamics
      of information acquisition and changes in executive cognitive control. Therefore,
      the present study intended to quantify and model the dynamic process of
      information acquisition during continuous overlearning of WM information. It also
      aimed at investigating the relation between overlearning-associated change in
      behavioral performance and brain activity. Thirteen schizophrenic patients and 13
      healthy volunteers were studied with functional magnetic resonance imaging (fMRI)
      while performing a recently developed overlearning paradigm [Koch K, Wagner G,
      von Consbruch K, Nenadic I, Schultz C, Ehle C, Reichenbach J, Sauer H, Schlosser
      R (2006) Temporal changes in neural activation during practice of information
      retrieval from short-term memory: An fMRI study. Brain Res 1107:140-150].
      Consistent with the earlier study, short-term learning of stimulus material was
      associated with significant performance improvements and exponential signal
      decreases in a fronto-parieto-cerebellar network both in schizophrenic patients
      and in healthy volunteers. Against expectation patients exhibited stronger signal
      decreases relative to controls in anterior cingulate (Brodmann area (BA) 32),
      middle and superior temporal (BA 37, BA 22), superior frontal (BA 8/9, BA 6) and
      posterior parietal regions (BA 40). Furthermore, the individually modeled
      exponential decay rate of the blood oxygenation level-dependent signal in the
      right dorsolateral prefrontal cortex was significantly correlated with
      exponential decrease in mean behavioral response times in healthy controls while
      a statistical trend emerged in patients. A relative hyperactivation in the
      patient group was observable only at the start of the learning process and
      diminished with continued overlearning. This effect might indicate a gradual
      reduction of recruited neuronal resources and a practice-associated activation
      normalization in patients with schizophrenia. Our data suggest that in subacute
      patients learning and associated decreases in cerebral activation brought about
      by short-term practice are left unimpaired.

PMID- 17448607
TI  - Acne vulgaris: nutritional factors may be influencing psychological sequelae.
AB  - Acne vulgaris is a distressing skin condition which can carry with it significant
      psychological disability. Patients with acne are more likely to experience anger
      and are at increased risk of depression, anxiety, suicidal ideation. Certain
      nutrients which have been implicated as influencing the pathophysiology of acne
      have also been identified as important mediators of human cognition, behavior and
      emotions. Zinc, folic acid, selenium, chromium and omega-3 fatty acids are all
      examples of nutrients which have been shown to influence depression, anger and/or
      anxiety. These same nutrients, along with systemic oxidative stress and an
      altered intestinal microflora have been implicated in acne vulgaris. It is our
      contention that certain nutritional factors, a weakened antioxidant defense
      system and altered intestinal microflora may interplay to increase the risk of
      psychological sequelae in acne vulgaris.

PMID- 17448606
TI  - The critical role of voltage-dependent calcium channel in axonal repair following
      mechanical trauma.
AB  - Membrane disruption following mechanical injury likely plays a critical role in
      the pathology of spinal cord trauma. It is known that intracellular calcium is a
      key factor that is essential to membrane resealing. However, the differential
      role of calcium influx through the injury site and through voltage dependent
      calcium channels (VDCC) has not been examined in detail. Using a well-established
      ex vivo guinea-pig spinal cord white matter preparation, we have found that
      axonal membrane resealing was significantly inhibited following transection or
      compression in the presence of cadmium, a non-specific calcium channel blocker,
      or nimodipine, a specific L-type calcium channel blocker. Membrane resealing was
      assessed by the changes of membrane potential and compound action potential
      (CAP), and exclusion of horseradish peroxidase 60 min following trauma.
      Furthermore, 1 microM BayK 8644, a VDCC agonist, significantly enhanced membrane
      resealing. Interestingly, this effect was completely abolished when the
      concentration of BayK 8644 was increased to 30 microM. These data suggest that
      VDCC play a critical role in membrane resealing. Further, there is likely an
      appropriate range of calcium influx through VDCC which ensures effective axonal
      membrane resealing. Since elevated intracellular calcium has also been linked to
      axonal deterioration, blockage of VDCC is proposed to be a clinical treatment for
      various injuries. The knowledge gained in this study will likely help us better
      understand the role of calcium in various CNS trauma, which is critical for
      designing new approaches or perhaps optimizing the effectiveness of existing
      methods in the treatment of CNS trauma.

PMID- 17448608
TI  - How did the ancestral HIV-1 group M retrovirus get to Leopoldville from
      southeastern Cameroon?
AB  - In previous papers in this journal, I have described and elaborated a hypothesis
      for the origin and evolution of a strain of HIV that has produced a lethal
      pandemic. Here I address the provocative question of how the ancestral HIV-1
      group M retrovirus got to Leopoldville (Kinshasa, where the pandemic clearly
      spawned) from southeastern Cameroon (where the HIV-1 strains all seemed to
      originate from transfer of SIV(cpz) to humans). Consistent with the phylogenetic
      history of HIV-1 group M (e.g., by Korber et al.), I place the critical
      relocation of the ancestral HIV-1 in the timeframe 1920-1927. However, unlike
      other hypotheses, I believe that the ancestral retrovirus was already well
      adapted to humans and can be identified as HIV-1 Group M subtype A(pre)-1927.
      Based on documents from that time period (1920-1928), it can be shown that it was
      not unusual for native Africans to be brought as far as 500 miles for treatment
      at the Leopoldville clinic (national borders were no issue because health
      agencies had mandate to work throughout Cameroon and Congo-Brazzaville).
      Specifically, sleeping sickness (trypanosomiasis) was one of the diseases of most
      concern at the Leopoldville clinic; in the period 1926-1928 there was an outbreak
      of sleeping sickness in Cameroon; and one of the native African children in the
      pamaquine (plasmoquineTM) study that I believe selected for the major HIV-1 group
      M subgroups had trypanosomiasis. Thus, this child (or other patients/relatives
      from Cameroon) could have brought the ancestral HIV-1 group M retrovirus to the
      Leopoldville laboratory and spread it among the group of children who were
      undergoing treatment for malaria between February and August 1927. The diagnosis
      and monitoring of these protozoan diseases (trypanosomiasis and malaria) involved
      repetitive sampling of blood, which provides many opportunities for spreading the
      ancestral HIV-1 infection.

PMID- 17448609
TI  - Effect of personality type on pharmacodynamics through changing pharmacokinetics.
AB  - A few studies have showed that there is an association between the genetic
      polymorphisms of drug-metabolizing enzyme, CYP2D6, to persons with different
      personality type. More and more evidences suggested that personality type is kind
      of behavioral or psychological factor which might influence the pharmacodynamics
      as well as patient's gender, age, disease, and genetic background. We
      hypothesized that personality affect the pharmacodynamics through changing
      pharmacokinetic mediated by different polymorphism of drug-metabolizing enzymes.
      Since many major diseases, from cancer to infectious disease, are involved with
      risky Type A personality, we appeal for attention to the clinical pharmacologist
      and psychiatrists further to study personality pharmacokinetics for
      individualized medicine.

PMID- 17448610
TI  - Consideration of use of phenothiazines in particular trifluorperazine for
      epidermal growth factor receptor associated cancers.
AB  - Papers from a generation ago suggested that phenothiazines--in particular
      trifluorperazine (Stelazine) a medicinal approved by the FDA and still commonly
      used for schizophrenia--downregulate the epidermal growth factor receptor. As
      numerous cancers--e.g., colon cancer, breast cancer, pancreatic cancer and
      glioblastoma--are dependent on signaling via this receptor, we here suggest that
      phenothiazines such as trifluorperazine be considered for use in epidermal growth
      factor receptor associated cancers.

PMID- 17448611
TI  - Nitric oxide synthase partial uncoupling as a key switching mechanism for the
      NO/ONOO- cycle.
AB  - Short-term stressors, capable of increasing nitric oxide levels, act to initiate
      cases of illnesses including chronic fatigue syndrome, multiple chemical
      sensitivity, fibromyalgia and posttraumatic stress disorder. These stressors,
      acting primarily through the nitric oxide product, peroxynitrite, are thought to
      initiate a complex vicious cycle mechanism, known as the NO/ONOO- cycle that is
      responsible for chronic illness. The complexity of the NO/ONOO- cycle raises the
      question as to whether the mechanism that switches on this cycle is this complex
      cycle itself or whether a simpler mechanism is the primary switch. It is proposed
      here that the switch involves a combination of two variable switches, the
      increase of nitric oxide synthase (NOS) activity and the partial uncoupling of
      the NOS activity, with uncoupling caused by a tetrahydrobiopterin (BH4)
      deficiency. NOS uncoupling causes the NOS enzymes to produce superoxide, the
      other precursor of peroxynitrite, in place of nitric oxide. Thus partial
      uncoupling will cause NOS proteins to act like peroxynitrite synthases, leading,
      in turn to increased NF-kappaB activity. Peroxynitrite is known to oxidize BH4,
      and consequently partial uncoupling may initiate a vicious cycle, propagating the
      partial uncoupling over time. The combination of high NOS activity and BH4
      depletion will lead to a potential vicious cycle that may be expected to switch
      on the larger NO/ONOO- cycle, thus producing the symptoms and signs of chronic
      illness. The role of peroxynitrite in the NO/ONOO- cycle also implies that such
      uncoupling is part of the chronic phase cycle mechanism such that agents that
      lower uncoupling will be useful in treatment.

PMID- 17448612
TI  - Could pathogens be nutrients for lymphoid cells?
AB  - Metabolic and immune systems are very important for a living organism to survive.
      Since they play crucial roles in maintaining homeostasis, both systems work
      interdependently. In metabolic disorders like obesity and related diseases, lot
      of reports have been published about immune system impairment. In addition, in
      the case of malnutrition and calorie restriction, immune system is affected
      through several mechanisms. Different from the current point of view, I propose
      an unusual way of thinking about the relationship between immune and metabolic
      systems. The nutrient-based ecosystemic balance; the simple desires and rules
      like feeding or reproduction underlying very complex relations among species; the
      beneficial effects of caloric restriction; and the similarities between the
      pathways contributing obesity and infection made me look from a different
      perspective. Based on ecology and systems thinking, the present hypotheses
      suggest that pathologic organisms could be a kind of dietary source for lymphoid
      cells. If it is true, it will bring new and hopeful insights to all events
      related to metabolic and immune systems. At first, new mechanisms could be
      improved to defeat unbeatable organisms like Mycobacterium tuberculosis or HIV.
      The unphagocytosed organisms could be unknown tastes for our body's defenders.
      For example, the lymphoid cells could be classified as virovores, bacterivores,
      or fungivores like herbivores, and carnivores. Secondly, this basic relation
      could be used to solve huge problems caused by obesity related disorders like
      diabetes, because insulin would play more important roles for lymphoid cells
      while regulating the blood glucose level if the hypothesis is true. And the
      persistence of hyperglycemia would mainly effect lymphoid cells according to the
      current hypothesis.

PMID- 17448613
TI  - Molecular characterization of novel variants of interferon-tau (IFNT) gene in
      Garole breed of sheep (Ovis aries).
AB  - The survivability of embryo, especially during the early embryonic life is
      dependent on the effective maternal recognition of pregnancy. Interferon-tau
      (IFNT), secreted from the elongating blastocyst, acts as the primary signal for
      maternal recognition of pregnancy in ruminant ungulates. IFNT has been studied
      extensively in many domesticated and wild ruminant species. In the present study,
      we have cloned and characterized the IFNT gene of Garole sheep, a popular Indian
      micro-sheep breed, which is known across the world for its high prolificacy and
      fecundity. The 588 bp sequences of two variants of IFNT gene described in this
      study are novel variants, compared to the variants reported previously in sheep.
      It exhibited more than 96% identity with other ovine IFNT variants and
      phylogenetically placed in a single clad containing the ovine, caprine and musk
      ox IFNT variants. The IFNT of Garole sheep demonstrated the highest identity with
      the genomic derived and highly expressed ovine IFNT variants.

PMID- 17448614
TI  - The intrapituitary endocrine events during maturation and timing of puberty in
      the female sheep.
AB  - The aim of this study was to determine the maturational activity of gonadotroph
      cells, the site of synthesis, storage and release of luteinizing hormone (LH) and
      follicle-stimulating hormone (FSH) in Polish Merino female sheep born after the
      summer solstice. The actual time of puberty of these lambs was delayed until the
      following breeding season, when they were 14 months old. Changes were examined in
      12 peripubertal (30-, 52-week-old) and pubertal (Days 15 and 17 of the second
      ovarian cycle) females. Histomorphological and functional changes in the
      gonadotroph population were assayed with hybridohistochemistry,
      immunohistochemistry, computer-assisted image analysis and radioimmunoassay. The
      percentage of the adenohypophyseal area (PAA) occupied by gonadotrophs containing
      LHbeta-mRNA was higher and the LH plasma concentration and pulse frequency were
      lower in the 52-week-old sheep in comparison with the 30-week-old sheep (P<0.05).
      The PAA occupied by immunoreactive (ir)-LHbeta-cells remained stable at the 30th
      and 52nd weeks of age and then increased at the pubertal follicular phase. The
      PAA occupied by ir-FSHbeta-cells was higher in the 52-week-old sheep compared
      with the 30-week-old sheep and then lower at the pubertal follicular phase
      (P<0.05). The PAA occupied by gonadotrophs containing LHbeta-mRNA or FSHbeta-mRNA
      was lower at the pubertal follicular phase in comparison with the 52nd week of
      age (P<0.05). In pubertal sheep, the PAA occupied by gonadotrophs containing
      LHbeta-mRNA or FSHbeta-mRNA was higher and the PAA occupied by ir-LHbeta or ir
      FSHbeta-cells was lower at the preovulatory phase in comparison with the
      follicular phase of the cycle (P<0.05). In conclusion, the photoperiodic
      suspension of gonadotroph population's maturational functions has been observed
      at the level of LH storage and release but not at the level of LH synthesis
      during the expected time of puberty in female sheep of an aseasonal breed such as
      Merino. The findings show the heterogeneity in the patterns of LH and FSH post
      transcriptional processing during the period of peripubertal/pubertal transition,
      explained by the different intrapituitary regulation at the level of post
      transcriptional synthesis and storage rather, than at the level of release.
      Altogether, intrapituitary mechanisms of ovine maturation could have the
      histomorphological feature. Our observations prompt the hypothesis that the
      female lamb may be able to transduce changes in day length into the appropriate
      endocrine cues for sexual maturation after attainment by the pituitary
      gonadotroph population the full peripubertal efficiency, manifested by the
      sufficient storage of LH.

PMID- 17448615
TI  - Temperature modulated drug permeation through liquid crystal embedded cellulose
      membranes.
AB  - Stimuli-sensitive membranes may act as "on-off switches" or "permeability
      valves", producing patterns of pulsatile release, where the period and rate of
      mass transfer can be controlled by external or environmental triggers. In this
      study, cellulose nitrate (CN) and cellulose acetate (CA) monolayer membranes
      containing thermotropic liquid crystals (LC) were developed as thermoresponsive
      barriers for drug permeation. A low molecular thermotropic LC, n-heptyl
      cyanobiphenyl (K21), with nematic to isotropic phase transition temperature (T(n
      i)) of 41.5 degrees C was chosen to modulate drug permeation. Methimazole and
      paracetamol as hydrophilic and hydrophobic drug models were used, respectively.
      It was found that upon changing the temperature of the system around the T(n-i),
      both cellulose membranes without LC showed no temperature sensitivity to drug
      permeation, whereas the results for LC entrapped membranes exhibited a distinct
      jump in permeability when temperature was raised to above the T(n-i) of the
      liquid crystal for both drug models. On the other hand, drug permeation through
      these LC embedded membranes can be thermally modulated. Thermoresponsive drug
      permeation through the membranes was reversible, reproducible and followed zero
      order kinetics. Liquid crystal embedded cellulose acetate membranes showed more
      temperature sensitivity than liquid crystal embedded cellulose nitrate membranes,
      apparently due to higher LC loading in their porous matrix compared to CN
      membranes. The pattern of on-off permeation through LC embedded membranes was
      more distinguished for methimazole compared to that of paracetamol, seemingly due
      to its lower molecular weight.

PMID- 17448616
TI  - Immuno-targeting of nonionic surfactant vesicles to inflammation.
AB  - Niosomes composed of sorbitan monostearate (Span 60), polyoxyethylene sorbitan
      monostearate (Tween 61), cholesterol, and dicetyl phosphate were conjugated with
      a purified monoclonal antibody to CD44 (IM7) through a cyanuric chloride (CC)
      linkage on the polyoxyethylene group of the Tween 61 molecule. Inclusion of small
      amounts of Tween 61 within the surfactant component of niosomes formed using thin
      film hydration techniques and sonication did not hamper vesicle stability as
      compared to Span 60 niosomes. Conjugation was verified by UV absorbance of
      fluorescently tagged IM7 in non-fluorescing niosomes and fluorescent micrographs.
      The immuno-niosomes were incubated with synovial lining cells expressing CD44.
      Attachment of niosomes was evident and showed selectivity and specificity
      compared to controls. These findings suggest that the resulting immuno-niosomes
      may provide an effective method for targeted drug delivery.

PMID- 17448617
TI  - Relaxivity of Gd-based contrast agents on X nuclei with long intrinsic relaxation
      times in aqueous solutions.
AB  - The relaxivity of commercially available gadolinium (Gd)-based contrast agents
      was studied for X-nuclei resonances with long intrinsic relaxation times ranging
      from 6 s to several hundred seconds. Omniscan in pure 13C formic acid had a
      relaxivity of 2.9 mM(-1) s(-1), whereas its relaxivity on glutamate C1 and C5 in
      aqueous solution was approximately 0.5 mM(-1) s(-1). Both relaxivities allow the
      preparation of solutions with a predetermined short T1 and suggest that in vitro
      substantial sensitivity gains in their measurement can be achieved. 6Li has a
      long intrinsic relaxation time, on the order of several minutes, which was
      strongly affected by the contrast agents. Relaxivity ranged from approximately
      0.1 mM(-1) s(-1) for Omniscan to 0.3 for Magnevist, whereas the relaxivity of Gd
      DOTP was at 11 mM(-1) s(-1), which is two orders of magnitude higher. Overall,
      these experiments suggest that the presence of 0.1- to 10-microM contrast agents
      should be detectable, provided sufficient sensitivity is available, such as that
      afforded by hyperpolarization, recently introduced to in vivo imaging.

PMID- 17448618
TI  - Upright MRI of glenohumeral dysplasia following obstetric brachial plexus injury.
AB  - The purpose of this study was to evaluate the role of upright magnetic resonance
      imaging (MRI) shoulder scanning in the diagnosis of glenohumeral deformity
      following obstetric brachial plexus injury (OBPI). Eighty-nine children (ages 0.4
      to 17.9 years) with OBPI who have medial rotation contracture and reduced passive
      and active lateral rotation of the shoulder were evaluated via upright MRI of the
      affected glenohumeral joint. Qualitative impressions of glenoid form were
      recorded, and quantitative measurements were made of glenoid version and
      posterior subluxation. Glenoid version of the affected shoulder averaged -16.8 +/
      11.0 degrees (range, -55 degrees to 1 degrees ), and percentage of the humeral
      head anterior to the glenoid fossa (PHHA) averaged 32.6 +/- 16.5% (range, -17.8%
      to 52.4%). The glenoid form was normal in 43 children, convex in 19 children and
      biconcave in 27 children. Standard MRI protocols were used to obtain bilateral
      images from 14 of these patients. Among the patients with bilateral MR images,
      glenoid version and PHHA were significantly different between the involved and
      uninvolved shoulders (P<.000). Glenoid version in the involved shoulder averaged 
      19.0 +/- 13.1 degrees (range, -52 degrees to -3 degrees ), and PHHA averaged 29.7
      +/- 18.4% (range, -16.2% to 48.7%). In the uninvolved shoulder, the average
      glenoid version and PHHA were -5.2 +/- 3.7 degrees (range, -12 degrees to -1
      degrees ) and 47.7 +/- 3.0% (range, 43% to 54%), respectively. The relative
      beneficial aspects of upright MRI include lack of need for sedation, low
      claustrophobic potential and, most important, natural, gravity-influenced
      position, enabling the surgeon to visualize the true preoperative picture of the
      shoulder. It is an effective tool for demonstrating glenohumeral abnormalities
      resulting from brachial plexus injury worthy of surgical exploration.

PMID- 17448619
TI  - Structural characterization of PEGylated rHuG-CSF and location of PEG attachment
      sites.
AB  - Mass spectrometry structural characterization is an essential tool in validating
      the quality of PEG-rHu-proteins. However, in either case top-down or bottom-up
      fashion, the interference of high intensity PEG signals on MS detection or
      detrimental influence of PEG on protein structure, leads to incomplete structural
      characterization. We propose here a method that permits complete and reliable
      structural characterization of PEGylated recombinant human granulocyte-colony
      stimulating factor (rHuG-CSF). The approach includes on-column 2-methoxy-4,5
      dihydro-1H-imidazole derivatization of digested PEG rHuG-CSF and subsequent LC/MS
      investigation. By comparing the LC/MS retention of derivatized and underivatized
      digested PEG rHuG-CSF, location of the PEG attachment within rHuG-CSF could be
      deduced. Besides, the protein sequence coverage and position of the disulfide
      bridges was fully deducible from the MS data interpretation. Additionally, ultra
      performance liquid chromatography-mass spectrometry-to-the-E (UPLC-MS(E)) was
      introduced for analysis of label-free digested PEG rHuG-CSF here to enable high
      resolution and mass accuracy of MS detection and facilitate deep structural
      insights of peptides.

PMID- 17448620
TI  - Factors in the doctor-patient relationship that accentuate physicians' hurt
      feelings when patients terminate the relationship with them.
AB  - OBJECTIVE: The present study explores the emotional effect of the injury
      experienced by physician's, as a consequence of a patient's termination of their
      relationship. METHODS: A vignette study using different scenarios describing a
      patient who switched to another doctor was distributed to 119 family physicians.
      A three-way ANCOVA analysis was employed. Additionally, physicians' answered an
      open question asking of situations that elicited negative emotions. RESULTS: The
      quantitative results indicated that termination of the relationship by a "high
      status" patient and/or after a long duration is more emotionally hurtful than
      termination by a "lower status" patient after a brief relationship. The results
      of the open question provided an additional insight into the emotional impact of
      the doctor's hurt feelings on the doctor-patient relationship. CONCLUSIONS: The
      severity and consequences of the emotional injury experienced by physicians when
      patients decide to transfer to another physician are influenced by factors
      related to the patient, physician and the relationship between them. PRACTICE
      IMPLICATIONS: We discuss the implications of our results on the understanding of
      the emotional injury and consequent impaired function and possible "burn-out" in
      physicians and explore the possibility of educating doctors to heightened
      awareness and consequently enhanced ability to cope with such situations.

PMID- 17448621
TI  - Can face-to-face patient education be replaced by computer-based patient
      education? A randomised trial.
AB  - OBJECTIVE: Computer-based patient education is an effective (therapeutic) tool.
      More and more studies prove that it can be an effective additive for face-to-face
      education, but it is still unclear if it is possible to educate patients by only
      using a computer. Our objective was to compare knowledge levels and satisfaction
      scores after computer-based patient education versus doctor-based patient
      education. METHODS: We started a randomised and stratified trial in a large
      plastic surgery clinic in the Netherlands. One hundred thirteen patients with
      carpal tunnel syndrome (CTS), scheduled for operation were included. One group
      received CTS education by a doctor using a checklist (group A). The other group
      received the same CTS education by specially designed interactive computer
      program (group B). After 2 weeks, knowledge levels and satisfaction scores were
      tested by using a questionnaire. RESULTS: One hundred thirteen patients were
      included, 96 patients finished the questionnaire. With respect to knowledge
      levels the doctor group (A) scored 20.2 points (max 40 points), and the computer
      group (B) scored 23.5 points. After correction the difference was 2.8 points
      (p=0.001). The total satisfaction score in group A was 7.6 and in group B 7.5; a
      difference of -0.16 (p=0.585). CONCLUSIONS: The results suggest that educating
      patients can result in a higher knowledge levels by using a computer than by
      using a doctor. Satisfaction seems equal after both methods of education.
      PRACTICE IMPLICATIONS: Knowing that you can educate patients without seeing a
      doctor or nurse seems promising. Patient can be educated by computer-based
      education programs leaving more time in a consultation for asking questions and
      discussing treatment options. The discussion will be at a more equal level of
      knowledge. Possibly it can save time and money resulting in a more efficient
      patient care, without dissatisfying our patients.

PMID- 17448622
TI  - Doctor-patient communication in primary care with an interpreter: physician
      perceptions of professional and family interpreters.
AB  - OBJECTIVE: This paper explores physician perceptions of the ways professional and
      family interpreters affect their performance of doctor-communication tasks
      described in the Calgary-Cambridge Framework. METHODS: Physicians' (19)
      encounters with patients (24) accompanied by an interpreter were videotaped.
      Stimulated recall was used to elicit each of the participants' perceptions of the
      clinical encounter. We analyzed transcriptions of the physician interviews using
      Atlas-ti software. RESULTS: Physicians perceived all communication tasks to be
      more difficult using an interpreter than when one was not needed. Physicians
      perceived family interpreters to be less skilled translators than professional
      interpreters. Physicians expected professional interpreters to serve as culture
      brokers at least some of the time. Although only some family interpreters were
      also caregivers, physicians assumed that all of them fulfilled caregiver roles.
      CONCLUSION: With professional interpreters, physicians follow communication rules
      they were taught. In contrast, physicians act as though these rules are not
      relevant with family interpreters who they treat as caregivers. PRACTICE
      IMPLICATIONS: Guidelines to working with an interpreter should include directives
      on working with both professional and family interpreters, describing the
      similarities and differences with each type, and modifying the clinical encounter
      process to correspond to those attributes.

PMID- 17448623
TI  - Elevated preoperative neutrophil to lymphocyte ratio predicts survival following
      hepatic resection for colorectal liver metastases.
AB  - BACKGROUND: The neutrophil-lymphocyte ratio (NLR) provides an indicator of
      inflammatory status. An elevated NLR has been shown to be a prognostic indicator
      in primary colorectal malignancy. The aim of this study was to establish whether
      NLR predicts outcome in patients undergoing resection for colorectal liver
      metastasis. DESIGN: Retrospective analysis of the white cell and differential
      counts for 440 patients undergoing liver resections for colorectal liver
      metastasis between January 1996 and January 2006. An NLR > or = 5 was considered
      to be elevated. RESULTS: Two hundred and eighty-nine males and 151 females were
      included. Seventy-eight patients (18%) had an elevated NLR, 55 of whom died,
      giving elevated NLR a positive predictive value (PPV) for death of 71%. Sixty of
      the 78 patients had recurrent disease giving raised NLR an PPV for recurrence of
      78%. The 5-year survival for patients undergoing resection with high NLR was
      significantly worse than that for patients with normal NLR (22% vs. 43%,
      p<0.0001). Univariate analysis of factors affecting survival revealed raised NLR,
      number of metastases > 8, tumour size > 5 cm and age > 70 significantly affected
      outcome. All factors except tumour size remained significant predictors of term
      survival on multivariate analysis (NLR:HR=2.261, CI=1.654-3.129, p<0.0001,
      metastases > 8:HR=1.611, CI=1.006-2.579, p=0.047, age > 70:HR=1.418, CI=1.049
      1.930, p=0.027). Elevated NLR was found to be the sole positive predictor of
      recurrence on univariate analysis (HR=4.521, CI=2.475-8.257, p<0.0001).
      CONCLUSION: Elevated NLR increases both risk of death and the risk of recurrence
      in patients who undergo surgery for CRLM. Preoperative NLR measurement may
      therefore provide a simple method of identifying patients with a poorer
      prognosis.

PMID- 17448624
TI  - Surgical planning for retrosigmoid craniotomies improved by 3D computed
      tomography venography.
AB  - OBJECTIVE: It is impossible to precisely anticipate the crooked course of the
      transverse and sigmoid sinuses and their individual relationship to superficial
      landmarks such as the asterion during retrosigmoid approaches. This study was
      designed to evaluate this anatomical relationship with the help of a surgical
      planning system and to analyze the impact of these in vivo findings on
      trepanation placement in retrosigmoid craniotomies. METHODS: In a consecutive
      series of 123 patients with pathologies located in the cerebellopontine angle, 72
      patients underwent surgical planning for retrosigmoid craniotomies based on 3D
      volumetric renderings of computed tomography venography. By opacity modulation of
      surfaces in 3D images the position of the asterion was assessed in relationship
      to the transverse-sigmoid sinus transition (TST) and compared to its
      intraoperative localization. We evaluated the impact of this additional
      information on trepanation placement. RESULTS: The spatial relationship of the
      asterion and the underlying TST complex could be identified and recorded in 66
      out of 72 cases. In the remaining 6 cases the sutures were ossified and not
      visible in the 3D CT reconstructions. The asterion was located on top of the TST
      in 51 cases, above the TST in 4 cases, and below the TST in 11 cases. The
      location of the trepanation was modified in 27 cases due to the preoperative
      imaging findings with major and minor modifications in 10 and 17 cases,
      respectively. CONCLUSION: Volume-rendered images provide reliable 3D
      visualization of complex and hidden anatomical structures in the posterior fossa
      and thereby increase the precision in retrosigmoid approaches.

PMID- 17448625
TI  - Lycopene affects proliferation and apoptosis of four malignant cell lines.
AB  - The beneficial effect of lycopene from tomatoes on a variety of chronic diseases
      and particularly its association with decreased incidence of prostate and breast
      cancer seems to be well established. The aim of the study was to examine its anti
      proliferative and apoptotic effect on other malignant cell lines. Cells of the
      following lines were incubated with 1.0, 2.0, and 4.0microM of lycopene: human
      colon carcinoma (HuCC), B chronic lymphocytic leukemia (EHEB), human
      erythroleukemia (K562) and Raji, a prototype of Burkitt lymphoma cell line. The
      results showed that lycopene exerted a significant dose-dependent effect on the
      proliferation capacity of K562, Raji and HuCC lines, whereas this effect was
      observed in EHEB cells only with the highest dose used in the study. Increased
      apoptotic rate was found after incubation of HuCC cells with 2.0 and 4.0microM of
      lycopene and in Raji cells following incubation with 2.0microM. The findings
      point out that the anti-proliferative effect of lycopene on tumor cells and its
      effect on the apoptotic rate depends on its dosage and on the type of the
      malignant cells.

PMID- 17448626
TI  - [Capital Souffle: results of a 2005 public awareness campaign about breath
      measurements in France].
AB  - AIM: A national public awareness campaign (Capital Souffle, or Breath Matters)
      about prevention and detection of chronic obstructive respiratory diseases was
      carried out in seven large French cities. The principal objective was to collect
      demographic and respiratory-related characteristics and increase population
      awareness of breath measurements for detecting chronic obstructive respiratory
      diseases, particularly asthma and chronic obstructive pulmonary disease (COPD).
      The secondary objective was to assess the immediate impact of lung function
      measurements on the subjects who participated in the campaign. METHODS: This
      multicenter cross-sectional survey was conducted in October and November 2005 in
      7 large French cities. Subjects completed 2 questionnaires, one collecting
      demographic and medical, especially respiratory-related, data and the second
      assessing subjects' response to the campaign. Data collection was completed by
      measurement of their FEV1/FEV6 ratio with an electronic pocket spirometer (PiKo
      6). RESULTS: Data from 8294 questionnaires could be analyzed: 14.4% of subjects
      reported having asthma and 4.1% COPD. Approximately 10% reported they were
      followed by a physician for a chronic respiratory disease. Half were current
      (28.5%) or former (21.9%) smokers, who began smoking at a median age of 17 years
      (10-50). The FEV1/FEV6 ratio was normal (>80%) in 79.4% of subjects, required
      further monitoring in 15.5% (70-80%) and abnormal (<70%) in 5.1%. In all 1416
      subjects (17.1%) had a FEV1/FEV6 ratio that was either abnormal or required
      follow-up and were not followed by a physician for respiratory disease. This
      campaign produced a high level of public awareness: 85.8% of subjects reported
      they wanted to know more about respiratory health, 64% said they would discuss it
      with their physician and 62.7% that the campaign would encourage them to take
      their medication. PERSPECTIVES: This survey demonstrates the feasibility of a
      national public awareness campaign about chronic respiratory diseases in France,
      based on a simple lung function measurement. The immediate impact of the campaign
      was high. Additional studies are necessary to determine the number of chronic
      respiratory disease diagnosed and managed by physicians.

PMID- 17448627
TI  - [The euthyroid sick syndrome in severe acute illness].
AB  - OBJECTIVE: To describe euthyroid sick syndrome (ESS) and its different clinical
      variants in severe acute illness. DESIGN: This prospective cohort study examined
      hormone results and outcome for patients admitted to our intensive care unit
      (ICU). METHODS: In this heterogeneous group of 108 patients from our ICU we
      analyzed the prevalence of ESS and its influence on mortality and sought to
      determine if any thyroid indicators had a prognostic value. RESULTS: The
      prevalence of ESS was similar to that described by other authors (68.5% for ESS
      type I, 15.7% for type II and 1.9% for type III). Patients developed thyroid
      alterations on their third day of hospitalization and those with ESS type II had
      a higher mortality rate. The only thyroid indicator with prognostic value was a
      reverse triiodothyronine (rT3) value exceeding 0.61 ng/mL. CONCLUSION: Severe
      acute illness induced the thyroid alterations known as ESS. Type I had the
      highest prevalence, but type II was correlated with a higher mortality rate. The
      only thyroid indicator with a prognostic value was rT3.

PMID- 17448628
TI  - [Breast cancer in men].
AB  - Breast cancer in men is rare and most often occurs at or after the age of 60
      years. Prognosis is poor when it is discovered at a late stage, as it often is in
      men, although it should be easier to detect because men have so little breast
      tissue. The causal mechanism appears to depend on hormone metabolism
      abnormalities related to elevated estrogen or prolactin levels. A family history
      of breast cancer is found in 5-10% of cases. Infiltrating ductal carcinoma
      accounts for most cases (70-90%) of male breast cancers. In situ but not invasive
      carcinoma is exclusively ductal and accounts for 7% of cases. Spread to lymph
      nodes is observed in 50-75% of cases. Immunohistochemical analysis shows that
      tumors are positive for progesterone and estrogen receptors more frequently in
      men than women. Diagnosis is based on clinical examination, ultrasonography, and
      mammography. Aspiration cytology often makes it possible to confirm the
      malignancy. Excisional biopsy with an immediate intraoperative pathology
      examination confirms malignancy and makes wider excision possible during the same
      procedure. A modified radical mastectomy with removal of some lymph nodes
      (Patey's mastectomy) is the standard basic treatment. Locoregional radiotherapy
      is very often indicated. Hormone therapy is also a first-line treatment.
      Chemotherapy is reserved for young men with substantial lymph node invasion and
      negative for hormonal receptors. The prognosis of breast cancer in men remains
      uncertain because of the frequently late diagnosis, unpredictable course, and
      high potential for metastasis.

PMID- 17448629
TI  - Trypanosoma cruzi cell invasion and traffic: influence of Coxiella burnetii and
      pH in a comparative study between distinct infective forms.
AB  - Previous studies have shown that Coxiella burnetii, an intracellular bacterium
      that resides within acidified vacuoles with secondary lysosomal characteristics,
      is an effective modulator of the intracellular traffic of trypomastigote forms of
      Trypanosoma cruzi. In addition, vacuolar and cellular pH are related to fusion
      events that result in doubly infected phagosomes. T. cruzi, the etiological agent
      of Chagas' disease, occurs as different strains grouped in two major phylogenetic
      lineages: T. cruzi I, associated with the sylvatic cycle, and T. cruzi II, linked
      to the human disease. In this work we compared extracellular amastigotes (EA),
      metacyclic trypomastigotes (MT) and tissue culture derived trypomastigotes (TCT)
      belonging to T. cruzi I or T. cruzi II for their ability to invade and escape
      from their parasitophorous vacuole (PV), in Vero cells or Vero cells harboring
      the bacterium, C. burnetti. Distinct invasion patterns were observed between
      different infective stages and between infective forms of different strains.
      Studies on the transference kinetics revealed that pH modulates the intracellular
      traffic of each infective stage, but this influence is not exclusive for each
      phylogenetic group. Endosomal to lysosomal sequential labeling with EEA-1 and
      LAMP-1 of the PV formed during the entry of each infective form revealed that the
      phagosome maturation processes are distinct but not strain-dependent. Due to
      their low hemolysin and trans-sialidase activities, MTs are retained for longer
      periods in LAMP-1 positive vacuoles. Our results thus suggest that despite the
      contrasting invasion capabilities, parasites of distinct phylogenetic group
      behave in similar fashion once inside the host cell.

PMID- 17448630
TI  - Regulation of RANKL and OPG gene expression in human gingival fibroblasts and
      periodontal ligament cells by Porphyromonas gingivalis: a putative role of the
      Arg-gingipains.
AB  - Porphyromonas gingivalis is highly implicated in the pathogenesis of
      periodontitis, which is characterized by the destruction of periodontal
      connective tissues and the supporting alveolar bone. Receptor Activator of NF
      kappaB Ligand (RANKL) stimulates bone resorption, whereas osteoprotegerin (OPG)
      blocks its action, and this bi-molecular system is implicated in periodontitis.
      The aim of this work was (a) to investigate the regulation of RANKL and OPG gene
      expression in human periodontal ligament (PDL) cells and gingival fibroblasts
      (GF), in response to P. gingivalis culture supernatants, by quantitative real
      time PCR and (b) to attempt to identify putative virulence factors involved in
      this process. The results indicated that P. gingivalis induced RANKL and reduced
      OPG mRNA expression by the studied cells, resulting in an increased RANKL/OPG
      expression ratio. Heat-inactivation of P. gingivalis resulted in significant
      reduction of RANKL mRNA expression. A Lys-gingipain mutant strain did not affect,
      whereas an Arg-gingipain mutant strain further enhanced RANKL mRNA expression,
      compared to their parental wild-type strain. In conclusion, P. gingivalis up
      regulates the RANKL/OPG expression ratio in GF and PDL cells, denoting an
      enhanced osteoclastogenic potential by the cells. The component mainly
      responsible for RANKL induction appears to be proteinaceous, and it may be
      regulated by the Arg-gingipains.

PMID- 17448631
TI  - Paroxetine reduces social anxiety in individuals with a co-occurring alcohol use
      disorder.
AB  - Patients with social anxiety disorder who are seen in clinical practice commonly
      have additional psychiatric comorbidity, including alcohol use disorders. The
      first line treatment for social anxiety disorder is selective-serotonin-reuptake
      inhibitors (SSRIs), such as paroxetine. However, the efficacy of SSRIs has been
      determined with studies that excluded alcoholics. Forty two subjects with social
      anxiety and a co-occurring alcohol use disorder participated in a 16-week, double
      blind, placebo-controlled clinical trial to determine the efficacy of paroxetine
      for social anxiety in patients with co-occurring alcohol problems. Paroxetine was
      superior to placebo in reducing social anxiety, as measured by the Liebowitz
      Social Anxiety Scale total and subscale scores and additional measures of social
      anxiety. This study provides the first evidence-based recommendation for the use
      of an SSRI to treat social anxiety in this patient population.

PMID- 17448632
TI  - The application of a polymerase chain reaction (PCR)-based capillary
      electrophoretic technique provides detailed insights into Eimeria populations in
      intensive poultry establishments.
AB  - Intestinal coccidiosis, caused by one or multiple species of Eimeria (Protozoa:
      Apicomplexa), is one of the most important infectious diseases affecting
      chickens. In this study, we used a polymerase chain reaction (PCR)-based
      capillary electrophoresis (CE) approach to conduct an epidemiological survey of
      Eimeria species in seven Australian broiler flocks, varying in age from 18 to 42
      days. We confirmed that all seven recognized Eimeria species of poultry were
      present. Eimeria acervulina and E. maxima were the most common, followed by E.
      mitis (i.e., 89%, 87% and 64% of chickens, respectively). E. praecox was present
      in 44% of birds, whereas E. brunetti and E. tenella were uncommon, being found in
      36% and 26%, respectively. E. necatrix was rarely detected (10%). Even the least
      common species were present in more than 70% of sheds. The prevalence of
      individual species was higher in older than in younger chickens. Most of the
      chickens sampled were simultaneously infected with multiple Eimeria species
      (mean=3.6). The number of Eimeria oocysts excreted per gram of faeces reached a
      peak at 36 days of age, before declining to a considerably lower level by 42
      days. As anticoccidial drugs were permanently withdrawn at 36 days, the
      decreasing Eimeria oocyst excretion rates indicated the development of protective
      immunity in the chickens. The present study showed that even healthy chickens
      usually harbour numerous species of Eimeria. The CE technique proved to be a time
      and cost-effective means of investigating the epidemiology of Eimeria in
      commercial establishments.

PMID- 17448633
TI  - Vascular injury and modulation of MAPKs: a targeted approach to therapy of
      restenosis.
AB  - Cardiovascular interventions that restore blood circulation to ischemic areas are
      accompanied by significant tissue damage, which triggers a vascular remodeling
      response that may result in restenosis of blood conduits. Early endothelial
      dysfunction and/or impairment is the early event of a cascade that leads, through
      an inflammatory response and dedifferentiation of medial smooth muscle cells with
      abundant deposition of extracellular matrix, to intimal hyperplasia. Here we
      present the molecular and cellular mechanisms of intimal hyperplasia secondary to
      vascular injury and discuss the potential role of therapeutic modulation of the
      intracellular signaling pathways that differentially effect vascular endothelial
      and smooth muscle cells. The role of mitogen-activated protein kinases (MAPKs)
      and the outcome of their modulation in these processes are highlighted here as
      they provide a promising therapeutic target for prevention of restenosis.

PMID- 17448634
TI  - Effects of active non-smoking programmes on smoking behaviour in oral precancer
      patients.
AB  - Smoking is the commonest risk factor for oral cancer and precancer. The objective
      of this study was to characterize smoking behaviour and attitude in a cohort of
      oral precancer patients in Newcastle upon Tyne, UK, and to determine changes in
      behaviour during diagnosis, treatment and follow-up. Twenty-seven consecutive,
      smoking patients with dysplastic oral lesions were recruited to the study and a
      detailed smoking history obtained, quantifying types and numbers of cigarettes
      smoked, length of smoking history, and changes in smoking behaviour during
      treatment episodes and long-term follow-up. All patients underwent an
      interventional management protocol comprising risk-factor education,
      histopathological diagnosis by incisional biopsy and laser excision of lesions.
      Patients were followed up for 5 years. Whilst there was a significant decrease in
      the number of cigarettes smoked at patients' most recent follow-up compared with
      initial presentation (p<0.001), 74% continued to smoke. Patients received advice
      from a smoking cessation adviser on support available to them from the local NHS
      (National Health Service) Stop Smoking services. Six out of 10 patients who set a
      'quit date' and attended a programme had quit at the 4-week follow-up but only 5
      remained non-smokers. Smoking remains a considerable problem in oral precancer
      patients even after interventional treatment, with the risk of further
      precancerous lesions and malignant transformation.

PMID- 17448635
TI  - Lack of differences of motorcortical excitability in the morning as compared to
      the evening in juvenile myoclonic epilepsy--a study using transcranial magnetic
      stimulation.
AB  - We used transcranial magnetic stimulation (TMS) in patients with juvenile
      myoclonic epilepsy (JME) and healthy controls to characterise motorcortical
      excitability in the morning as compared to the evening. Intra- and
      interindividual comparisons in JME-patients and controls showed no significant
      differences of any TMS parameter. The expected rise of the resting motor
      thresholds (RMT) in JME-patients taking anticonvulsants could not be detected
      which may indicate a decreased RMT in JME-patients.

PMID- 17448636
TI  - The effect of sodium valproate on proton MRS visible neurochemical
      concentrations.
AB  - The effect of the antiepileptic medication sodium valproate (VPA) on the
      concentrations of cerebral metabolites was studied longitudinally in ten patients
      with epilepsy using proton magnetic resonance spectroscopy (MRS). Myo-inositol
      was found to be lower while taking VPA, although no relationship between the
      change in metabolite concentration, VPA dose or seizure control was observed. MRS
      findings should be interpreted in the light of administered medications.

PMID- 17448637
TI  - Temporal lobe seizure semiology during wakefulness and sleep.
AB  - We used regression analysis to compare the semiologic features of temporal lobe
      seizures that occur during sleep (TLS-S) and wake (TLS-W) in the same patient.
      Most semiologic features correctly lateralized seizure activity during either
      sleep or wake. No significant differences were found between TLS-S and TLS-W in
      the 18 semiologic features analyzed. The diagnostic value of TLS-S semiology is
      similar to that of TLS-W semiology.

PMID- 17448638
TI  - Optical suppression of seizure-like activity with an LED.
AB  - The therapy of focal epilepsy remains unsatisfactory for as many as 25% of
      patients. We tested the hypothesis that an efficient, ultraviolet light emitting
      diode (UV LED), coupled with a newly developed "caged" gamma-aminobutyric acid
      (GABA), might be capable of terminating "ictal-like" events in cultured murine
      neurons. GABA was released from BC204, a recently described caged GABA, using a
      small, ultraviolet (UV) LED. Ictal-like events were provoked by removal of
      extracellular magnesium. In preliminary control experiments, the concentration of
      GABA released from our caged compound was dependent upon the strength and
      duration of the illumination, and readily achieved micromolar (microM) levels
      that are known to activate tonic, extrasynaptic GABA(A) receptors. Ultraviolet
      illumination had no effect when BC204 was not present in the perfusate and the
      currents produced by BC204 were eliminated by picrotoxin. Within a few seconds of
      UV illumination, BC204 rapidly terminated ictal-like events at low microM
      concentration. Uncaging of BC204 also blocked the elevation of intracellular
      calcium induced by seizure-like discharges in our cultures. While much more
      technical development is clearly required to extend our observations to a more
      intact preparation, these results suggest the intriguing possibility of
      constructing an implantable device to "optically suppress" focal human seizures
      under closed loop control.

PMID- 17448639
TI  - Evaluation of carisbamate, a novel antiepileptic drug, in photosensitive
      patients: an exploratory, placebo-controlled study.
AB  - PURPOSE: Carisbamate, a novel neuromodulatory agent with antiepileptic
      properties, was evaluated in patients with photoparoxysmal responses to
      intermittent photic stimulation (IPS) in this multicenter, non-randomized, single
      blind, placebo-controlled, proof-of-concept study. METHODS: Eighteen Caucasian
      patients (14 females, 4 males) with a mean age of 30 years (range: 16-51 years)
      underwent standardized IPS under three eye conditions (during eye closure, eyes
      closed and eyes open) at hourly intervals for up to 8h after receiving placebo
      (Day 1), carisbamate (Day 2) and placebo (Day 3). Carisbamate was given at single
      doses of 250-1000 mg. All patients received one or two concomitant antiepileptic
      drugs, most commonly valproate. RESULTS: Carisbamate produced a dose-dependent
      reduction in photosensitivity in the 13 evaluable patients, with abolishment of
      photoparoxysmal responses in 3 patients and clinically significant suppression of
      such responses in 7 additional patients. Photosensitivity was abolished or
      reduced in all five patients in the 1000-mg dose group. The onset of carisbamate
      occurred rapidly, with clinically significant suppression achieved before or near
      the time peak plasma drug levels were reached. The duration of action was dose
      related and long-lasting, with clinically significant reductions of
      photosensitivity observed for up to 32 h after doses of 750 or 1000 mg.
      Carisbamate was generally well tolerated, with dizziness and nausea reported more
      frequently after active drug than placebo. CONCLUSION: This study shows that
      carisbamate exhibits dose-related antiepileptic effects in the photosensitivity
      model. Randomized, controlled studies of carisbamate in epilepsy patients
      inadequately controlled by their existing AED therapy are warranted.

PMID- 17448640
TI  - Vascular risk factors and oxidative stress as independent predictors of
      asymptomatic atherosclerosis in adult patients with epilepsy.
AB  - PURPOSE: This study aimed to evaluate the carotid artery intima-media thickness
      (CA-IMT) in adult patients with epilepsy and its contribution to oxidative stress
      and vascular risk biomarkers. METHODS: This study included 225 adult epileptic
      and 60 control subjects. For all, CA-IMT, fasting lipid profile (TC, TG, HDL-c
      and LDL-c), total homocysteine (tHcy), von Willbrand factor (vWF), fibrinogen,
      oxidized LDL (Ox-LDL), malondialdehyde (MDA), thiobarbituric acid reactive
      substances (TBARs), uric acid, total antioxidant capacity (TAC) and glutathione
      peroxidase (GSH.Px), were assessed. RESULTS: Compared to control group, the IMT
      of patients' common carotid artery, bifurcation area and internal carotid
      arteries was significantly thickened in 51.1%, 73.3% and 43.6% in various groups
      of patients (treated and untreated). In the studied patients, the levels of tHcy,
      vWF, fibrinogen, MDA, TBARs, Ox-LDL levels were increased while HDL-c and TAC
      were decreased. Patients on CBZ showed the most significant changes in the levels
      of tHcy, vWF and HDL-c while patients on VPA showed significant alteration in
      uric acid, TBARs and GSH.Px. CONCLUSION: This study supports that in patients
      with epilepsy, various vascular risk factors and CA-IMT, get worse which could be
      attributed to epilepsy itself and/or its antiepileptic medications.

PMID- 17448641
TI  - Usefulness of intracranial EEG in the decision process for epilepsy surgery.
AB  - BACKGROUND AND PURPOSE: In patients with discordant results, non-localizing EEG,
      or bitemporal seizure onset, intracranial monitoring is done to confirm the
      seizure onset. Our aim was to assess the yield of intracranial recordings in
      patients with different clinical scenarios. METHODS: The records of all patients
      who underwent prolonged intracranial EEG monitoring (IEM) at the London Health
      Sciences Centre, University of Western Ontario, Canada, between 1993 and 1999,
      identified using our EEG patient database in continuous use since December 1972,
      were reviewed. Patients were analyzed in the following groups according to
      perceived increasing degrees of uncertainty of epileptic zone localization-group
      1: lesion on MRI congruent with focal ictal and interictal scalp EEG, but
      findings are subtle and of low level of certainty (n=13), group 2: focal MRI,
      focal ictal and multifocal interictal scalp EEG (n=11), group 3: focal MRI, non
      localizing or incongruent scalp EEG (n=73), group 4: normal of multifocal MRI,
      focal ictal scalp EEG (n=11), group 5: multifocal MRI, non-localizing scalp EEG
      (n=18), and group 6: normal MRI, multifocal scalp EEG (n=36). RESULTS: One
      hundred and seventy one patients underwent IEM at the London Health Sciences
      Centre between 1993 and 1999. All patients had localization-related epilepsy,
      plus or minus secondary generalization. IEM was helpful overall in 86% of
      patients, in 69% of group 1, 36% of group 2, 90% of group 3, 81% of group 4, 100
      of group 5 and 92% of group 6. CONCLUSIONS: Our study shows that the yield of the
      IEM was higher in the groups of patients with lack of congruence between the MRI
      and the scalp EEG. The yield was lower in patients with congruent but subtle or
      uncertain scalp EEG and MRI findings.

PMID- 17448643
TI  - Anti-convulsant effect of electrical stimulation and lesioning of the anterior
      thalamic nucleus on kainic acid-induced focal limbic seizure in rats.
AB  - PURPOSE: We examined the effect of electrical stimulation and lesioning of the
      anterior nucleus of the thalamus (ANT) on focal limbic seizures induced by
      intraamygdaloid kainic acid (KA) injection in a rat model. To address the
      mechanism underlying these anti-convulsant actions, cerebral glucose metabolism
      following ANT electrical stimulation and lesioning was also assessed. METHODS:
      Wistar rats were divided into five major groups: control, unilateral and
      bilateral ANT electrical stimulation, and unilateral and bilateral ANT lesioning.
      After KA injection, average clinical-seizure frequencies in each group were
      measured. Local cerebral glucose utilization (LCGU) was also measured using
      [(14)C] 2-deoxyglucose autoradiography in three groups: control, ANT electrical
      stimulation and ANT lesioning. RESULTS: Animals subjected to ANT electrical
      stimulation and lesioning exhibited significantly decreased mean seizure
      frequency and secondary generalized seizure frequency, compared with control
      animals. In control-group, LCGU was markedly increased at both the limbic and
      corticothalamic circuits sites. While in ANT stimulation or lesioning-group,
      there was significant reduction in LCGU at the corticothalamic circuit sites, but
      not so considerable decrease at the limbic structures. CONCLUSION: ANT electrical
      stimulation and lesioning in the focal limbic seizure model were effective on
      convulsive seizures and secondary generalization, specifically with respect to
      the severity of these seizures.

PMID- 17448642
TI  - The validity of epilepsy or seizure documentation in nursing homes.
AB  - Recent studies have reported that epilepsy and seizures are common in nursing
      homes. Prevalence has been reported to range from 5 to 9% and antiepileptic drug
      (AED) use is even more common. Most of these studies have relied on various forms
      of nursing home records, but the validity of this source data, while assumed, has
      not been verified. This study evaluated the degree of agreement between the
      Minimum Data Set (MDS), both paper and electronic versions, and actual medical
      records available at the nursing home. Records of 144 residents were evaluated;
      agreement between paper and electronic versions of the MDS was 97.8%. Agreement
      between the paper version of the MDS and neurologists review of the nursing home
      record was 92.3%. However, the criteria for diagnosing epilepsy or seizure were
      not well documented. Nevertheless, the agreement among nursing home records,
      paper MDS and electronic MDS is great enough to allow the electronic MDS to be
      used as a research tool, but more investigation of the actual criteria used by
      nursing home physicians in diagnosing epilepsy and seizures is necessary.

PMID- 17448644
TI  - Heterogeneity in recovery of psychosocial functioning during psychiatric
      rehabilitation: an exploratory study using latent growth mixture modeling.
AB  - Research in schizophrenia and related severe mental illness (SMI) suggests that
      psychiatric rehabilitation facilitates recovery of psychosocial functioning
      although there is considerable heterogeneity in outcomes. The present study used
      growth mixture modeling (GMM), a longitudinal latent variable modeling strategy,
      to identify classes of psychosocial functioning recovery trajectories. Archival
      clinical assessment data representing the first 18 months of an inpatient
      psychiatric rehabilitation program were analyzed from a sample of participants
      with schizophrenia spectrum disorders (N=162). Based on a GMM analysis of monthly
      Nurse Observation Scale for Inpatient Evaluation (NOSIE) scores two classes were
      identified that differed in overall level of psychosocial functioning, rate and
      nonlinear shape of change. The identified lower functioning group was
      characterized by poorer neurocognitive functioning at admission, a history of
      negative symptoms, more previous inpatient psychiatric days, and a longer length
      of stay in the rehabilitation program. However, this group showed significantly
      greater positive change in the NOSIE domains directly targeted by behavioral
      treatment: daily schedule competence, neatness, and irritability. Methodological
      and theoretical implications of these modeling strategies are discussed in the
      context of understanding the rehabilitation process.

PMID- 17448645
TI  - High genotypic diversity of Pseudomonas aeruginosa strains isolated from patients
      with cystic fibrosis in the Czech Republic.
AB  - Over the last decade, epidemic and frequently multidrug-resistant Pseudomonas
      aeruginosa has increasingly been found among European cystic fibrosis (CF)
      patients. In the Czech Republic, more than half of the registered CF patients
      attend the Prague CF centre. At this centre, a Burkholderia cenocepacia strain
      was recently found to have spread among the patients. The aim of the present
      study was to assess whether P. aeruginosa isolates from patients at this centre
      were also genetically related and, if so, whether they were multidrug-resistant.
      We investigated a collection of 69 isolates from as many patients who represented
      80% of the total number of P. aeruginosa-positive patients in 2004. The organisms
      were typed by AFLP and SpeI macrorestriction analyses (PFGE). Using these
      methods, 44 unique strains and nine groups of two to five isolates each were
      distinguished. Among these groups, two each had a prevalence of 7% in the patient
      population, while others had a prevalence of < or =3%. The diversity observed
      with PFGE was largely in agreement with the diversity found by AFLP analysis. All
      isolates were susceptible to colistin; 94-96% were susceptible to piperacillin,
      ceftazidime, cefepime, meropenem, amikacin or tobramycin; and 84-87% were
      susceptible to ciprofloxacin, gentamicin or netilmicin. In conclusion, the
      organisms recovered from Czech CF patients showed high genotypic diversity and
      good susceptibility to antipseudomonal agents. The absence of highly epidemic P.
      aeruginosa strains may result from infection control measures taken upon
      recognition of the epidemic B. cenocepacia.

PMID- 17448646
TI  - Effect of drying on extruded pellets based on kappa-carrageenan.
AB  - kappa-Carrageenan is a new pelletisation aid for the wet extrusion/spheronisation
      process. Its promising behavior during pelletisation offers a potential
      replacement of the commonly used microcrystalline cellulose in several
      formulations. Due to its high water binding, the drying step of the pelletisation
      has gained increasing attention. Therefore, a systematic investigation of the
      effect of drying conditions on pellet properties was the aim of this study.
      Pellets with different formulations were dried in fluid bed, circulation-, and
      vacuum oven and then characterized by mean dissolution time, tensile strength and
      disintegration time. Increasing the temperature and duration of the drying
      process decreased the mean dissolution time, tensile strength and disintegration
      time of the pellets. The observed effects were attributed to a cautious
      decomposition of the kappa-carrageenan above 70 degrees C. Furthermore an ionic
      interaction between calcium ions of dicalciumphosphate and sulfate ester groups
      of kappa-carrageenan affected the pellet properties like drug release.

PMID- 17448647
TI  - When should the seminal vesicles be included in the target volume in prostate
      radiotherapy?
AB  - External beam radiotherapy to the prostate and seminal vesicles as a radical
      treatment for prostate cancer can result in a significant dose being delivered to
      the rectum. This can be reduced if the target volume includes the prostate only.
      Using a Medline search, published studies are reviewed to show that the risk of
      seminal vesicle involvement can be accurately predicted using readily available
      pre-treatment parameters. We recommend when to exclude the seminal vesicles from
      a target volume, and the proportion of seminal vesicles that should be included
      in a target volume in higher risk patients.

PMID- 17448648
TI  - Endothelin, PAF and thromboxane A2 in allergic pulmonary hyperreactivity in mice.
AB  - The role of endothelin, PAF and thromboxane A2 in airway hyperreactivity (AHR) to
      carbachol induced by ovalbumin sensitization and challenge in Balb/c mice was
      investigated. Ovalbumin sensitization and challenge induced significant AHR to
      carbachol in actively sensitized and challenged mice. Treatment of these mice
      with the PAF antagonist CV-3988 (10 microg kg(-1), i.v.) completely abolished OVA
      induced AHR to carbachol. Treatment of sensitized mice with the TxA2 antagonist L
      654,664 (1 mg kg(-1), i.v.) partially blocked the induction of AHR in OVA
      challenged mice. The intranasal administration of 50 pmol of the ET(A) receptor
      antagonist BQ-123 had no effect on the PIP but produced a significant reduction
      at the dose of 100 pmol. The intravenous administration of BQ-123 (100 pmol)
      reduced the PIP only at the highest doses of carbachol. The ET(B) receptor
      antagonist BQ-788 administered either via the intranasal or intravenous route had
      no effect on the PIP at the dose of 100 pmol. Naive mice treated with either U
      44069 (25 or 100 microg kg(-1), i.v.), endothelin-1 (100 pmol, intranasally) or
      the ET(B) receptor agonist IRL-1620 (100 pmol, intranasally) showed a marked
      increase in airway reactivity to carbachol. These results suggest an important
      role for endothelin, PAF and thromboxane A2 in AHR in mice actively sensitized
      and challenged with ovalbumin.

PMID- 17448649
TI  - Telephone consultations in secondary care.
AB  - OBJECTIVE: To determine the role of telephone consultations in respiratory
      medicine. DESIGN: An observational study. SETTING: Respiratory outpatients
      department in an inner London teaching hospital. PARTICIPANTS: Five-hundred
      sequential patients attending three different outpatient respiratory clinics.
      INTERVENTION: Substitution of the next intended consultation with a telephone
      consultation. OUTCOME MEASURES: Proportion of patients suitable for telephone
      consultation, their availability when telephoned, length of consultation and
      patient satisfaction. CONCLUSIONS: Telephone consultations are an effective
      alternative to traditional consultations in a third of respiratory patients
      attending for hospital follow-up. This style of consultation allows the option of
      not attending the hospital for a consultation and 23.9% had their consultation at
      their place of work.

PMID- 17448650
TI  - A randomized study comparing ciclesonide and fluticasone propionate in patients
      with moderate persistent asthma.
AB  - OBJECTIVE: To compare the effects of once-daily ciclesonide and twice-daily
      fluticasone propionate in patients with moderate persistent asthma. METHODS:
      Patients aged 12-75 years with moderate bronchial asthma entered a 1-4 week run
      in period. For inclusion into the 12-week, randomized, open-label treatment
      period, patients had to have a forced expiratory volume in 1s (FEV1) of either 60
      80% of predicted or 80% of predicted and a defined use of rescue medication and
      asthma symptoms, depending on previous treatment. Patients received ciclesonide
      320 microg once daily (ex-actuator) or fluticasone propionate 200 microg twice
      daily. Primary efficacy endpoint was change from baseline in FEV1. RESULTS: In
      total, 474 patients were randomized. FEV1 increased significantly from baseline
      with ciclesonide and fluticasone propionate in the intention-to-treat (ITT) and
      per-protocol (PP) analyses (all p < 0.0001). Treatment difference was -31 mL (95%
      confidence interval [CI]: -121, 59) in the PP analysis, demonstrating non
      inferiority of ciclesonide. Similar findings were seen for other measures of lung
      function. In the ITT population, asthma symptom scores and rescue medication use
      decreased with both treatments (all p < 0.0001). Improvement in health-related
      quality of life (HRQoL) from baseline was significantly greater with ciclesonide
      than fluticasone (p = 0.005; one-sided). There were no cases of oral candidiasis
      in patients receiving ciclesonide and nine cases (3.8%) in those receiving
      fluticasone propionate (p = 0.002; one-sided). CONCLUSIONS: Treatment with once
      daily ciclesonide and twice-daily fluticasone propionate resulted in similar
      improvements in lung function in patients with moderate persistent asthma.
      Ciclesonide showed significant improvements in oral candidiasis and HRQoL over
      fluticasone.

PMID- 17448651
TI  - Use of spirometry and patterns of prescribing in COPD in primary care.
AB  - OBJECTIVE: To investigate the use and interpretation of spirometry in primary
      care (PC) in the diagnosis of chronic obstructive pulmonary disease (COPD) and to
      identify the treatment schedules administered. METHODS: An observational study
      was performed in a randomized sample of 251 PC physicians including 2130 patients
      with COPD. Data on the performance of spirometry and the results and the
      treatment administered were collected as were sociodemographic and clinical data.
      RESULTS: Spirometric results were obtained in 1243 (58.4%). Most (1118/1243;
      89.9%) corresponded to FEV1 (%) values with a mean of 57% (SD=21.5%). It is of
      note that only 31.8% of spirometric results provided post-bonchodilator results,
      and 42.9% and 43.1% of the spirometries presented not plausible FVC or FEV1
      values, respectively. Treatment varied greatly, with more than 3 drugs being
      prescribed in 30.6% of the cases. Long-acting beta-2 agonists and inhaled
      corticosteroids were prescribed in more than 50% of the patients. Tiotropium was
      administered in 32.4%. According to the GOLD guidelines, 22.8% of the patients in
      GOLD II, 50% in III and 66.7% in IV were receiving incorrect treatment.
      CONCLUSIONS: Only 58.4% of the cases included had undergone spirometry. Important
      deficiencies were observed in the interpretation of the results of spirometry.
      These difficulties may influence the low implementation of treatment guidelines
      in COPD in PC.

PMID- 17448652
TI  - Effect of sleep on patient/ventilator asynchrony in patients undergoing chronic
      non-invasive mechanical ventilation.
AB  - BACKGROUND: Patients who require home non-invasive ventilation (NIV) during sleep
      normally have the ventilation settings adjusted empirically during daytime
      wakefulness. However, patient-ventilator asynchrony may occur during sleep. To
      detect the incidence of ineffective efforts (IE) during the sleep compared to
      wakefulness, we studied 48 patients already enrolled in a long-term home NIV
      programme. METHODS: We evaluated arterial blood gases, breathing pattern during
      spontaneous breathing (SB) and ventilation during wakefulness. In addition, we
      assessed the breathing pattern and oxygen gas exchange during night-time NIV.
      RESULTS: Daytime NIV significantly improved blood gases compared to SB (PaO2 NIV
      10.2 +/- 1.95 kPa vs PaO2 SB 8 +/- 1.37, p < 0.001; PaCO2 NIV 5.75 +/- 1.08 kPa,
      vs PaCO2 SB 6.5 +/- 1.25, p < 0.001). The IE index was higher during sleep
      compared to wakefulness (48 +/- 39.5 events/h versus 0 +/- 0). The IE index was
      correlated with the time spent with SaO2 < 90% (r = 0.39, p < 0.01), but not with
      ventilator parameters, underlying disease, ventilation mode or type of mask.
      Eight patients had an IE index >100 events/h; these patients had a faster
      respiratory rate, required a higher level of inspiratory assistance and had poor
      gas exchange during sleep. CONCLUSIONS: We conclude that IE to breath are common
      during nocturnal NIV and that they may be associated with desaturations even in
      patients who are considered compliant and effectively treated.

PMID- 17448653
TI  - Quantification of angiogenesis by the Chalkley method and its prognostic
      significance in epithelial ovarian cancer.
AB  - AIM: The aim of the present study was to clarify prognostic role of angiogenesis
      in epithelial ovarian cancer. METHODS: Quantification of angiogenesis was
      performed by the Chalkley method after immunostaining of 175 epithelial ovarian
      cancer specimens with an antibody against CD34. RESULTS: The Chalkley count was
      categorised into two groups according to the median value: low <8 or high > or
      =8. The low Chalkley count correlated significantly with serous and clear cell
      histological subtype of the tumour (p<0.0005), whereas there existed no
      association with FIGO (International Federation of Gynecology and Obstetrics)
      stage, histological grade, presence of primary residual tumour, age at diagnosis,
      or chemotherapy response. In univariate analysis, the high Chalkley count
      predicted poor overall survival in the subgroup of patients with FIGO stages III
      IV tumours (p=0.007) but not in the entire study cohort. However, in multivariate
      analysis, the Chalkley count was found to be an independent predictor of death
      from ovarian cancer in the entire study cohort (p=0.044, RR=1.50, 95% CI 1.01
      2.21) as well as in the subgroup of FIGO stages III-IV tumours (p=0.046, RR=1.58,
      95% CI 1.01-2.46) together with the presence of primary residual tumour
      (p<0.0005, RR=5.10, 95% CI 3.02-8.62, and p=0.002, RR=4.28, 95% CI 1.34-13.73,
      respectively). CONCLUSIONS: The Chalkley count seems to be suitable for
      evaluation of angiogenesis and to have prognostic significance in ovarian cancer.

PMID- 17448654
TI  - Evaluation of a new peat-based sorbent for metals capture.
AB  - A new peat-based sorbent was evaluated for the capture of heavy metals from waste
      streams. The media is a pelletted blend of organic humic material targeted for
      the capture of soluble metals from industrial waste streams and stormwater. The
      metals chosen for the media evaluation were Cd, Cu, Ni, and Zn due to their
      occurrence and abundance in waste streams and runoff. Sorption tests included an
      evaluation of the rate and extent of metals capture by the media, single versus
      multicomponent metals uptake, pH, anion influence, leaching effects and the
      effect of media moisture content on uptake rate and capacity. Isotherms of the
      sorption results showed that the presence of multiple metals increased the total
      sorption capacity of the media compared to the single component metal capacity; a
      result of site selectivity within the media. However the capacity for an
      individual metal in a multicomponent metal matrix was reduced compared to its
      single component capacity, due to competition for sites. Evidence of ion exchange
      behavior was observed but did not account for all metals capture. The media also
      provided a buffering action to counter the pH drop typically associated with
      metals capture.

PMID- 17448655
TI  - Statistical optimization of culture conditions for 1,3-propanediol by Klebsiella
      pneumoniae AC 15 via central composite design.
AB  - A central composite design was used to study the effect of glycerol, rate of
      stirring, air aeration and pH on the synthesis of 1,3-propanediol (1,3-PD) by
      Klebsiella pneumoniae AC 15. Among the four variables, glycerol and rate of
      stirring significantly affected 1,3-PD productivity, whereas air aeration and pH
      were not effective. A quadratic polynomial equation was obtained for 1,3-PD
      productivity by multiple regression analysis using response surface methodology.
      The validation experimental confirmed with the predicted model. The optimum
      combinations for 1,3-PD productivity was glycerol, rate of stirring, air
      aeration, and pH of 50 g/l, 318 rpm, 0.6 vvm, 6.48, respectively. The subsequent
      fed batch experiments produced 1,3-PD of 70 g/l at a fermentation of 30 h.

PMID- 17448656
TI  - Bridged androstenediol analogs as ER-beta selective SERMs.
AB  - A series of bridged androstenediol derivatives was prepared. The bridged
      compounds exhibited reduced ER-beta selectivity relative to uncyclized analogs.

PMID- 17448657
TI  - Chipping at large, potent human T-cell leukemia virus type 1 protease inhibitors
      to uncover smaller, equipotent inhibitors.
AB  - The human T-cell leukemia virus type 1 (HTLV-I) causes adult T-cell leukemia and
      several severe chronic diseases. HTLV-I protease (PR) inhibition stops the
      propagation of the virus. Herein, truncation studies were performed on potent
      octapeptidic HTLV-I PR inhibitor KNI-10161 to derive small hexapeptide KNI-10127
      with some loss in activity. After performing residue-substitution studies on
      compound KNI-10127, HTLV-I PR inhibitory activity was recovered in inhibitor KNI
      10166.

PMID- 17448658
TI  - Discovery and optimization of a series of quinazolinone-derived antagonists of
      CXCR3.
AB  - A series of quinazolinone-derived inhibitors of the CXCR3 receptor have been
      synthesized and their affinity for the receptor evaluated. Compounds were
      evaluated in a (125)I-IP10 displacement assay and in in vitro cell migration
      assays to IP10, ITAC, and MIG using human peripheral blood mononuclear cells.

PMID- 17448659
TI  - Design and synthesis of novel hydantoin-containing melanin-concentrating hormone
      receptor antagonists.
AB  - We report here new chemical series acting as antagonists of melanin-concentrating
      hormone receptor 1 (MCHR-1). Synthesis and structure-activity relationships are
      described leading to the identification of compounds with optimized in vitro
      pharmacological and in vitro ADME profiles. In vivo activity has been
      demonstrated in animal models of food intake and depression.

PMID- 17448660
TI  - Squalene-derived flexible linkers for bioactive peptides.
AB  - A regiochemical and stereochemical mixture of flexible linkers bearing terminal
      azide functionality was synthesized in two steps from squalene and was used to
      connect two high affinity NDP-alpha-MSH ligands or two low affinity MSH(4)
      ligands. The ligands were N-terminally acylated using N-hydroxysuccinimidoyl 5
      hexynoate and were subsequently attached to the linker via copper-catalyzed
      'click' 3+2 cyclization of the azide and alkyne moieties. In vitro biological
      evaluations showed that the binding affinity to the human melanocortin 4 receptor
      was not diminished for most linker-ligand combinations relative to the
      corresponding parental ligand. Statistical and cooperative binding effects were
      observed for dimeric constructs containing the low affinity ligand MSH(4), but
      not for dimeric NDP-alpha-MSH constructs, presumably due to slow off rates for
      this high affinity ligand.

PMID- 17448661
TI  - Five-year survival from breast cancer in Western Australia over a decade.
AB  - The aim of the present study was to investigate whether 5-year survival of
      patients with breast cancer in Western Australia has improved over time. We used
      a population-based study conducted in the State of Western Australia, to identify
      all cases of invasive breast cancer cases diagnosed in 1989, 1994 and 1999.
      Information on presentation, investigation and management was extracted from
      medical records of each case and status at 5 years after date of diagnosis was
      determined. Comparison of 5-year overall survival for women diagnosed in the
      three calendar years, and hazard ratios for survival calculated for prognostic
      variables were measured. We found that survival from breast cancer has improved
      in Western Australia since 1989. Earlier diagnosis, living in the Perth
      metropolitan area and use of breast-conserving surgery are associated with better
      survival, irrespective of year of diagnosis. Further research needs to be carried
      out to determine the reason for this improvement.

PMID- 17448662
TI  - Management of pain in cardiac surgery ICU patients: have we improved over time?
AB  - This study described the pain experience of cardiac surgery ICU patients. After
      their transfer to the surgical unit, 93 patients were interviewed using a
      questionnaire about their pain experience while they were in the ICU. Sixty-one
      patients (65.6%) recalled being ventilated and 72 patients (77.4%) recalled
      having pain. Turning was the most frequent source of pain experienced by the
      patients. A large proportion of the patients (47.3%) identified the thorax as the
      location of their pain. All patients had a sternal incision. Pain was mild for 16
      patients, moderate for 21, and severe for 25 of them. While ventilated, head
      nodding and movements of the upper limbs were the most frequent means of
      communication used by the patients. Despite advances in pain management, the
      study's findings are disturbingly similar to those of 17 years ago [Puntillo KA.
      Pain experiences of intensive care unit patients. Heart Lung 1990;19:526-33].
      Evidence from research about clinical guidelines for pain management needs to be
      applied to the care of cardiac surgery patients in order to reduce patient
      suffering.

PMID- 17448663
TI  - eMovie: a storyboard-based tool for making molecular movies.
AB  - The 3D structures of macromolecules are difficult to grasp and also to
      communicate. By their nature, movies or animations are particularly useful for
      highlighting key features by offering a 'guided tour' of structures and
      conformation changes. However, high-quality movies are rarely seen because they
      are currently difficult and time consuming to make. By adopting the traditional
      movie 'storyboard' concept, which gives guidance and direction to filming, eMovie
      makes the creation of lengthy molecular animations much easier. This tool is a
      plug-in for the open-source molecular graphics program PyMOL, and enables experts
      and novices alike to produce informative and high-quality molecular animations.

PMID- 17448664
TI  - Synthesis of 1,3-diphenyl-2-propen-1-one derivatives and evaluation of their
      biological activities.
AB  - A simple synthesis and biological properties of 1,3-diphenyl-2-propen-1-ones 18
      22 and 25-26 are described. The key synthetic strategies involve Grignard
      reaction of aldehyde 2 and oxidation reaction of 8-12 in high yields. The
      prepared compounds 18-22 and 25-26 were evaluated for free-radical scavenging,
      suppression of LPS-induced NO generation, and anti-excitotoxicity in vitro. It
      was found that a couple of compounds, especially 21 and 26, were potent
      suppressors of NO generation and demonstrated anti-excitotoxicity with the
      concentration range 10-20 microM in vitro.

PMID- 17448665
TI  - Synthesis procedure for routine production of 2-[18F]fluoro-3-(2(S)
      azetidinylmethoxy)pyridine (2-[18F]F-A-85380).
AB  - 2-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]F-A-85380) was among the
      first subtype selective radioligands to visualise the in vivo distribution of
      alpha4beta2-containing neuronal nicotinic acetylcholine receptors (nAChRs) in
      human brain. We developed a one-pot synthesis for the preparation of 2-[18F]F-A
      85380 in a commercially available TRACERlab FXF-N synthesis module. The synthesis
      comprises a nucleophilic substitution followed by hydrolysis of a t
      butyloxycarbonyl (BOC)-protected intermediate. After formulation for intravenous
      application up to 20 G Bq 2-[18F]F-A-85380 were produced from a starting activity
      of 100 G Bq [18F]fluoride in 60 min with a specific activity of about
      4.10(5)GBq/mmol and a mean radiochemical purity of more than 99%.

PMID- 17448666
TI  - Re: low grade malignant fibrosarcoma of the dental follicle of an unerupted third
      molar clinical evidence of any follicular lesion.

PMID- 17448667
TI  - Analysis of the orbital floor morphology.
AB  - INTRODUCTION: For the repair of large orbital floor defects due to blow-out
      fractures or those involved by tumours, it is necessary to understand the
      detailed morphology. The purpose of the present study was to elucidate how age
      and gender affect its three-dimensional morphology. METHODS: The 3-D computer
      tomography data of 305 orbits of 182 patients were included in the study. Using
      the CT data, the orbital floor angle (the angle between the orbital floor and the
      horizontal plane) and the location of the most inferior point of the orbital
      floor were measured. Patients were classified into subgroups according to their
      gender and age. Data were compared among the subgroups. RESULTS: The orbital
      floor angle was greater in males than in females, and in children than in adults.
      The location of the lowest point of the orbital floor moves postero-inferiorly
      with increasing age. CONCLUSION: The present study demonstrated that gender and
      age affects morphology of the orbital floor. These findings should be useful for
      reconstruction of the orbital floor.

PMID- 17448668
TI  - Condyle as the point of rotation for 3-D planning of distraction osteogenesis for
      hemifacial microsomia.
AB  - AIM: The purpose of this study is to present an exact simulation method for
      mandibular rotational movement in distraction osteogenesis for hemifacial
      microsomia. METHODS: Three-dimensional (3-D) surgery simulation software
      programmes (V-Works and V-Surgery; Cybermed, Seoul, Korea) were used, based on 3
      D CT data in addition to the conventional data, which included facial
      photography, panoramic radiograph, cephalogram, and dental models. After
      measuring the mandibular deficiency (horizontal and vertical) from a 3-D model
      reconstructed using the software, the angulation of the distraction device to the
      mandibular border (posterior or inferior) was determined. The rotation axis in
      the V-Works simulation was defined as the line perpendicular to the plane made by
      condylion and the distraction vector location on the mandible. The mandible moves
      along the plane around this rotational axis during distraction. After the 3-D
      simulation with the software programme, mock surgery on a rapid prototyping model
      was performed. This planning method was applied to models of two hemifacial
      microsomia patients. RESULTS: With this protocol, it was possible to simulate the
      rotational movement of the mandible on the axis passing through the condylar head
      of the unaffected side. CONCLUSION: The sequential planning procedure presented
      in this paper is considered to be helpful in performing effective preoperative
      simulation of distraction osteogenesis for hemifacial microsomia.

PMID- 17448669
TI  - Development and biomechanical testing of a new osteosynthesis plate (TCP)
      designed to stabilize mandibular condyle fractures.
AB  - INTRODUCTION: In this paper, the different steps of development and experimental
      validation of a new type of three-dimensional (3-D) trapezoidal osteosynthesis
      plate (Modus TCP 2.0, Medartis, Basel, Switzerland) is described. These plates
      have been designed to stabilize sub-condylar and condylar neck fractures of the
      mandible. MATERIAL AND METHODS: In order to apply the principles of functionally
      stable osteosynthesis to the mandibular condyle, i.e. to put the plate as close
      as possible to the tensile strain lines occurring during function, two new 4- and
      9-hole 3-D trapezoidal plates were designed. Tests were conducted on fresh human
      mandibles before and after osteosynthesis of a standardised unilateral sub
      condylar 'fracture', and a static biting exercise between the ipsilateral first
      molars was reproduced on a test bench. The resulting condylar fragment
      displacement in the sagittal plane was measured and the alterations of the
      condylar tensile strain lines induced by the osteosynthesis were investigated by
      using photoelastic strain tests. RESULTS: None of the plates broke. No
      macroscopic condylar displacement was noted when assessing the quality of the
      primary stabilization. Strain analysis showed the ability of these 3-D plates to
      transmit physiological strains across the fracture line and the absence of
      potentially damaging strains around the plate. DISCUSSION: These results were
      accredited to the 3-D and trapezoidal features of the plates. CONCLUSION: The
      Modus TCP plates experimentally fulfil the principles of functionally stable
      osteosynthesis in the condylar region and are able to resist physiological
      strains.

PMID- 17448670
TI  - Traumatic right ventricular rupture.

PMID- 17448671
TI  - ESTS guidelines for preoperative lymph node staging for non-small cell lung
      cancer.
AB  - Accurate preoperative staging and restaging of mediastinal lymph nodes in
      patients with non-small cell lung cancer (NSCLC) is of paramount importance. It
      will guide choices of treatment and determine prognosis and outcome. Over the
      last years, different techniques have become available. They vary in accuracy and
      procedure-related morbidity. The Council of the ESTS initiated a workshop on
      preoperative mediastinal lymph node staging. This resulted in guidelines for
      primary staging and restaging. For primary staging, mediastinoscopy remains the
      gold standard for the superior mediastinal lymph nodes. Invasive procedures can
      be omitted in patients with peripheral tumors and negative mediastinal positron
      emission tomography (PET) images. However, in case of central tumors, PET hilar
      N1 disease, low fluorodeoxyglucose uptake of the primary tumor and LNs > or = 16
      mm on CT scan, invasive staging remains indicated. PET positive mediastinal
      findings should always be cyto-histologically confirmed. Transbronchial needle
      aspiration (TBNA), ultrasound-guided bronchoscopy with fine needle aspiration
      (EBUS-FNA) and endoscopic esophageal ultrasound-guided fine needle aspiration
      (EUS-FNA) are new techniques that provide cyto-histological diagnosis and are
      minimally invasive. Their specificity is high but the negative predictive value
      is low. Because of this, if they yield negative results, an invasive surgical
      technique is indicated. However, if fine needle aspiration is positive, this
      result may be valid as proof for N2 or N3 disease. For restaging, invasive
      techniques providing cyto-histological information are advisable despite the
      encouraging results supported with the use of PET/CT imaging. Both endoscopic
      techniques and surgical procedures are available. If they yield a positive
      result, non-surgical treatment is indicated in most patients.

PMID- 17448672
TI  - Some variations of the circle of Willis, important for cerebral protection in
      aortic surgery--a study in Eastern Europeans.
AB  - BACKGROUND: During unilateral selective cerebral perfusion (SCP), via cannulation
      of the brachiocephalic trunk, the brain receives blood only through the right
      common carotid artery and the right vertebral artery. For perfusion of the
      contralateral (left) hemisphere it is counted on the competence of the circle of
      Willis (CoW). It is well known that variations of CoW are present in more than
      50% of the people. Furthermore, these variations usually affect more than one
      vessel of the circle. The aim of the present work was to study the variations of
      CoW, which could have an impact on cerebral blood supply during unilateral SCP.
      METHODS AND MATERIALS: We study 112 CoWs obtained from cadavers via routine
      dissection in the Department of Forensic Medicine of Medical University, Sofia.
      The external diameter of both vertebral arteries and all arteries that form CoW
      was measured with a caliper-gauge. RESULTS: We identify the variations of CoW
      such as significant hypoplasy and/or lack of a branch of the circle. Bearing in
      mind the characteristics of the blood flow during unilateral SCP some of these
      variations were classified as significant during unilateral SCP. They were
      subdivided into groups according to most probable stroke site after unilateral
      SCP. CONCLUSIONS: Because of the high percent of the variations, hemodynamically
      significant during unilateral SCP, a suggestion for routine preoperative CT-angio
      of CoW could be made. Furthermore, an intraoperative follow-up with NIRO,
      transcranial Doppler, EEG, and so forth could also be recommended.

PMID- 17448673
TI  - Deuterium kinetic isotope effects in microsolvated gas-phase E2 reactions.
AB  - This work describes the first experimental studies of deuterium kinetic isotope
      effects (KIEs) for the gas-phase E2 reactions of microsolvated systems. The
      reactions of F(-)(H(2)O)(n) and OH(-)(H(2)O)(n), where n = 0, 1, with
      (CH(3))(3)CX (X = Cl, Br), as well as the deuterated analogs of the ionic and
      neutral reactants, were studied utilizing the flowing afterglow-selected ion flow
      tube technique. The E2 reactivity is found to decrease with solvation. Small,
      normal kinetic isotope effects are observed for the deuteration of the alkyl
      halide, while moderately inverse kinetic isotope effects are observed for the
      deuteration of the solvent. Minimal clustering of the product ions is observed,
      but there are intriguing differences in the nature and extent of the clustering
      process. Electronic structure calculations of the transition states provide
      qualitative insight into these microsolvated E2 reactions.

PMID- 17448674
TI  - Efficient and reliable calculation of Rice-Ramsperger-Kassel-Marcus unimolecular
      reaction rate constants for biopolymers: modification of Beyer-Swinehart
      algorithm for degenerate vibrations.
AB  - The Beyer-Swinehart (BS) algorithm, which calculates vibrational state density
      and sum, was modified for simultaneous treatment of degenerate vibrations. The
      modified algorithm was used in the grouped-frequency mode of the Rice-Ramsperger
      Kassel-Marcus (RRKM) unimolecular reaction rate constant calculation for proteins
      with relative molecular mass as large as 100,000. Compared to the original BS
      method, reduction in computation time by a factor of around 3000 was achieved.
      Even though large systematic errors arising from frequency grouping were observed
      for state densities and sums, they more or less canceled each other, thus
      enabling reliable rate constant calculation. The present method is thought to be
      adequate for efficient and reliable RRKM calculations for any macromolecule in
      the gas phase such as the molecular ions of proteins, nucleic acids, and
      carbohydrates generated inside a mass spectrometer. The algorithm can also be
      used to calculate the internal energy distribution of a macromolecule at thermal
      equilibrium.

PMID- 17448675
TI  - Detection of attomole amounts of analyte by desorption electrospray ionization
      mass spectrometry (DESI-MS) determined using fluorescence spectroscopy.
AB  - We report the use of fluorescence spectroscopy to investigate the amount of
      material removed from a PTFE surface and detected during desorption electrospray
      ionization (DESI) mass spectrometry measurements. The fluorescence intensity
      before and after DESI analysis of rhodamine 6G is used to determine the amount of
      material removed from the surface per mass spectrum. Calculations indicate low
      attomole amounts are removed per linear ion trap mass spectrum.

PMID- 17448676
TI  - Recombinant expression and purification of the N-terminal extracellular domain of
      the parathyroid hormone receptor.
AB  - Our goal is to elucidate the nature of the bimolecular interaction of parathyroid
      hormone (PTH) with its receptor, the parathyroid hormone receptor type-1 (PTHR1).
      In order to study this interaction, we are aiming to obtain a three-dimensional
      structure of the PTH-PTHR1 bimolecular complex. Due to the very low expression
      levels of endogenous PTHR1, a recombinant form is required for structural
      analysis. However, the extreme hydrophobicity of the transmembrane regions of
      PTHR1 makes heterologous expression of PTHR1 difficult. Therefore, we sought to
      express the N-terminal extracellular domain (N-ECD) of PTHR1, a region that plays
      a pivotal role in ligand interaction. We expressed the N-ECD in both bacterial
      (Escherichia coli) and insect (Sf9) cells. The form produced in E. coli, a fusion
      protein with thioredoxin, is soluble. However, removal of the fusion partner from
      a partially purified preparation results in dramatic loss of yield of the N-ECD.
      Expression in Sf9 cells, however, facilitates purification of a soluble form of
      the N-ECD. Isothermal calorimetry demonstrates that this N-ECD binds PTH-(1-34),
      albeit with lower affinity than the full-length receptor. This report describes
      the expression and purification of milligram quantities of the isolated N-ECD of
      PTHR1. The receptor fragment retains the ability to bind its cognate peptide
      ligand, an important pre-requisite for subsequent structural studies.

PMID- 17448677
TI  - Sociodemographic status, stress, and risk of prostate cancer. A prospective
      cohort study.
AB  - PURPOSE: The social gradient in prostate cancer incidence observed in several
      studies may be a result of differential access to prostate cancer screening. We
      aim to assess if socioeconomic status, stress, and marital status are associated
      with prostate cancer risk in a population with free access to health care.
      METHODS: The 5,496 men who participated in the Copenhagen City Heart Study were
      asked about their income, educational level, stress level, and marital status
      during 1981-1983. These men were prospectively followed up in the Danish Cancer
      Registry until the end of 2002 and fewer than 0.1 % were lost to follow-up.
      RESULTS: During follow-up, 157 men were diagnosed with prostate cancer. Neither
      high income (HR = 1.17, 95% confidence interval [CI]: 0.78-1.76) nor high
      education (HR = 1.22; 95% CI: 0.76-1.96) were associated with risk of prostate
      cancer. There were also no differences in prostate cancer risk according to
      stress (HR = 0.99; 95% CI: 0.90-1.09) or marital status. CONCLUSION: In a
      racially homogeneous population of Caucasians with free access to health care, we
      found no evidence of a relation between sociodemographic variables or stress and
      subsequent risk of prostate cancer.

PMID- 17448678
TI  - Endometriosis among women exposed to polybrominated biphenyls.
AB  - PURPOSE: We examined the association between endometriosis and exposure to
      polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) among women
      inadvertently exposed to PBBs in 1973. METHODS: Serum PBBs and PCBs were measured
      in the late 1970s. Women self-reported endometriosis at interview in 1997. We
      constructed Cox models to estimate the relative incidence of endometriosis in
      relation to PBB and PCB levels. RESULTS: Seventy-nine of 943 women (9%) reported
      endometriosis. Compared with women with low PBB exposure (<or=1 parts per billion
      [ppb]), women with moderate PBB (1-4 ppb) (hazard ratio [HR] = 0.72; 95%
      confidence interval [CI], 0.39-1.31) and high PBB (>or=4 ppb) (HR = 0.90; 95% CI,
      0.51-1.59) exposure did not have increased incidence of endometriosis. Increased
      incidence of endometriosis was suggested among women exposed to moderate PCB (5-8
      ppb) (HR = 1.67; 95% CI, 0.91-3.10) and high PCB (>or=8 ppb) (HR = 1.68; 95% CI,
      0.95-2.98) levels compared with low PCB exposure (<or=5 ppb). CONCLUSIONS: Our
      study does not support an association between PBB exposure and endometriosis.
      Findings for serum PCB level are consistent with an emerging body of literature
      suggesting an association between PCB exposure and endometriosis.

PMID- 17448679
TI  - Place of residence effect on likelihood of surviving prostate cancer.
AB  - PURPOSE: To examine geographic variation in survival time of men diagnosed with
      prostate cancer, adjusted for patient and disease characteristics. METHOD:
      Survival times for a geographically referenced database of 27,189 incident
      prostate cancer cases (ICD-O-2: C61.9) from Connecticut, 1984-1998, were
      evaluated using a newly developed extension of the spatial scan statistic for
      survival data. RESULTS: Statewide, median survival time was 4.6 years following
      diagnosis. Age-adjusted survival times across most locales around Connecticut did
      not differ markedly from the statewide pattern, but our analysis revealed 3 zones
      with noteworthy differences. Analysis of survival times adjusted for age as well
      as tumor grade and stage produced only two locations with significant results,
      and further adjustment for racial composition of cases yielded only one location
      with significant distinct (lower) survival times. Among cases within that place,
      the likelihood of dying was estimated to be 1.39-times greater than that of cases
      different from those diagnosed elsewhere around the state (p = 0.009).
      CONCLUSION: The prognosis for men with prostate cancer may differ, in part, by
      virtue of where they live when diagnosed. Measuring geographic differences in
      survival time should facilitate the targeting of clinical and ancillary services
      to persons at high risk of poor outcomes.

PMID- 17448680
TI  - Bladder cancer in perfluorooctanesulfonyl fluoride manufacturing workers.
AB  - PURPOSE: To determine whether bladder cancer is associated with exposure to
      perfluorooctane sulfonate (PFOS) in an occupational cohort. METHODS: Incidence of
      bladder cancer was ascertained by postal questionnaire to all living current and
      former employees of the facility (N = 1895) and death certificates for deceased
      workers (N = 188). Exposure to PFOS was estimated with work history records and
      weighted with biological monitoring data. Standardized incidence ratios (SIRs)
      were estimated using U.S. population-based rates as a reference. Bladder cancer
      risk within the cohort was evaluated using Poisson regression by cumulative PFOS
      exposure. RESULTS: Questionnaires were returned by 1,400 of the 1895 cohort
      members presumed alive. Eleven cases of primary bladder cancer were identified
      from the surveys (n = 6) and death certificates (n = 5). The SIRs were 1.28 (95%
      confidence interval [CI] = 0.64-2.29) for the entire cohort and 1.74 (95% CI =
      0.64-3.79) for those ever working in a high exposed job. Compared with employees
      in the lowest cumulative exposure category, the relative risk of bladder cancer
      was 0.83 (95% CI = 0.15-4.65), 1.92 (95% CI = 0.30-12.06), and 1.52 (95% CI =
      0.21-10.99). CONCLUSIONS: The results offer little support for an association
      between bladder cancer and PFOS exposure, but the limited size of the population
      prohibits a conclusive exposure response analysis.

PMID- 17448681
TI  - Risk of betel quid chewing on the development of liver cirrhosis: a community
      based case-control study.
AB  - PURPOSE: The role of betel quid on the development of liver cirrhosis is unclear;
      we thus designed a community-based case-control study to evaluate the association
      between betel quid chewing and liver cirrhosis. METHODS: A total of 42 cases of
      liver cirrhosis and 165 matched controls were included for analysis.
      Questionnaires were administered to obtain histories of betel quid chewing,
      alcohol consumption, smoking, and family history of liver disease. Hepatitis B
      surface antigen and anti-hepatitis C antibody were also determined by
      immunoassay. RESULTS: Individuals with more betel quid chewing (more than 55 quid
      years vs. less than 55 quid-years and never-chewers, matched odds ratio [OR(m)] =
      2.2; 95% confidence interval [CI]: 1.0-5.0) had higher risks for liver cirrhosis.
      The combined effects on liver cirrhosis by betel quid chewing and the number of
      other risk factors, including hepatitis B virus (HBV) infection, smoking, and
      alcohol drinking, were also observed. When individuals with less betel quid
      chewing (less than 55 quid-years and never-chewers) and with no other risk
      factors used as a reference, betel quid chewers expressing greater betel quid
      chewing (more than 55 quid-years) and more risk factors of HBV infection,
      cigarette smoking, and habitual alcohol drinking expressed a greater risk of
      liver cirrhosis (OR(m) = 70.8; 95% CI: 4.0-1260.1). CONCLUSIONS: Our results
      suggest that betel quid chewing may play an important role in the development of
      hepatic cirrhosis. Larger study and cohort studies would be necessary to provide
      further evidence regarding this finding.

PMID- 17448682
TI  - Increasing United States hospital admissions for acute pancreatitis, 1988-2003.
AB  - PURPOSE: To examine the epidemiology of hospital admissions for acute
      pancreatitis in the United States. METHODS: We compiled data from the 1988-2003
      National Hospital Discharge Survey and analyzed it with respect to patient
      demographics, hospital type and region, procedures performed, length of hospital
      stay, and inpatient mortality. RESULTS: Hospital admissions for acute
      pancreatitis increased from a 1988 low of 101,000 (95% confidence interval [CI]:
      87,000-116,000) to a 2002 peak of 210,000 (95% CI: 186,000-234,000). The
      corresponding admission rate increased from 0.4 to 0.7 hospitalizations per 1000
      U.S. population (p = 0.001). The patients' average age was 53 years, 51% were
      male, and 23% were black. The hospitalization rate was higher among blacks (0.9;
      95% CI, 0.6-1.1) than among whites (0.4; 95% CI, 0.3-0.5). The mean length of
      stay was 6.9 days and decreased over the study period. Overall mortality was 2%,
      with increasing age and male gender comprising independent risk factors for
      death. CONCLUSIONS: The hospitalization rate for acute pancreatitis in the United
      States is rising and is higher in blacks than in whites. Further research is
      necessary to identify the cause(s) of increasing pancreatitis admissions, the
      observed racial disparity, and the cost of these admissions.

PMID- 17448683
TI  - Positional accuracy and geographic bias of four methods of geocoding in
      epidemiologic research.
AB  - PURPOSE: We examined the geographic bias of four methods of geocoding addresses
      using ArcGIS, commercial firm, SAS/GIS, and aerial photography. We compared
      "point-in-polygon" (ArcGIS, commercial firm, and aerial photography) and the
      "look-up table" method (SAS/GIS) to allocate addresses to census geography,
      particularly as it relates to census-based poverty rates. METHODS: We randomly
      selected 299 addresses of children treated for asthma at an urban emergency
      department (1999-2001). The coordinates of the building address side door were
      obtained by constant offset based on ArcGIS and a commercial firm and true ground
      location based on aerial photography. RESULTS: Coordinates were available for 261
      addresses across all methods. For 24% to 30% of geocoded road/door coordinates
      the positional error was 51 meters or greater, which was similar across geocoding
      methods. The mean bearing was -26.8 degrees for the vector of coordinates based
      on aerial photography and ArcGIS and 8.5 degrees for the vector based on aerial
      photography and the commercial firm (p < 0.0001). ArcGIS and the commercial firm
      performed very well relative to SAS/GIS in terms of allocation to census
      geography. For 20%, the door location based on aerial photography was assigned to
      a different block group compared to SAS/GIS. The block group poverty rate varied
      at least two standard deviations for 6% to 7% of addresses. CONCLUSION: We found
      important differences in distance and bearing between geocoding relative to
      aerial photography. Allocation of locations based on aerial photography to census
      based geographic areas could lead to substantial errors.

PMID- 17448684
TI  - The crystal structure of DR2241 from Deinococcus radiodurans at 1.9 A resolution
      reveals a multi-domain protein with structural similarity to chelatases but also
      with two additional novel domains.
AB  - A unique family of proteins have been identified in the Deinococcus genus with an
      N-terminal cobalamin (vitamin B(12)) chelatase domain denoted CbiX and an
      additional unique C-terminal domain with unknown function. Here we report the
      first crystal structure from this new family of proteins with the structure of
      Deinococcus radiodurans protein DR2241. The structure reveals a multi-domain
      protein where domains A (residues 1-132) has the same fold as the small CbiX
      (CbiX(S)), domains A and B (residues 1-272) follow the chelatase super-family
      fold and the two additional unique domains C and D have no structural homologues.
      Domain D harbours the sequence motifs CxxC and CxxxC, in which DR2241 gives the
      first evidence that these motifs bind a [4Fe-4S] iron-sulphur cluster. In
      solution there are indications of multimeric forms, and in the crystallographic
      asymmetric unit a tetramer is found where domains C and D are involved in
      stabilising the tetrameric assembly.

PMID- 17448685
TI  - Gender disparities in the quality of cardiovascular disease care in private
      managed care plans.
AB  - BACKGROUND: Studies have shown that women with cardiovascular disease (CVD) are
      screened and treated less aggressively than men and are less likely to undergo
      cardiac procedures. Research in this area has primarily focused on the acute
      setting, and there are limited data on the ambulatory care setting, particularly
      among the commercially insured. To that end, the objective of this study is to
      determine if gender disparities in the quality of CVD care exist in commercial
      managed care populations. METHODS: Using a national sample of commercial health
      plans, we analyzed member-level data for 7 CVD quality indicators from the
      Healthcare Effectiveness Data and Information Set (HEDIS) collected in 2005. We
      used hierarchical generalized linear models to estimate these HEDIS measures as a
      function of gender, controlling for race/ethnicity, socioeconomic status, age,
      and plans' clustering effects. RESULTS: Results showed that women were less
      likely than men to have low-density lipoprotein (LDL) cholesterol controlled at
      <100 mg/dL in those who have diabetes (odds ratio [OR], 0.81; 95% confidence
      interval [CI], 0.76-0.86) or a history of CVD (OR, 0.72; CI 95%, 0.64-0.82). The
      difference between men and women in meeting the LDL control measures was 5.74%
      among those with diabetes (44.3% vs. 38.5%) and 8.53% among those with a history
      of CVD (55.1% vs. 46.6%). However, women achieved higher performance than men in
      controlling blood pressure (OR, 1.12; 95% CI, 1.02-1.21), where the rate of women
      meeting this quality indicator exceeded that of men by 1.94% (70.8% for women vs.
      68.9% for men). CONCLUSIONS: Gender disparities in the management and outcomes of
      CVD exist among patients in commercial managed care plans despite similar access
      to care. Poor performance in LDL control was seen in both men and women, with a
      lower rate of control in women suggesting the possibility of less intensive
      cholesterol treatment in women. The differences in patterns of care demonstrate
      the need for interventions tailored to address gender disparities.

PMID- 17448686
TI  - A quantitative study of the hepatic eosinophilic granule cells and rodlet cells
      during the breeding cycle of Ohrid trout, Salmo letnica Kar. (Teloestei,
      Salmonidae).
AB  - Fundamental questions remain on the nature and role of fish eosinophilic granule
      cells (EGCs) and rodlet cells (RCs). A poorly studied aspect is their suspected
      seasonality of occurrence under normal circumstances. In the liver of female
      Ohrid trout, Salmo letnica, we detected EGCs and RCs associated with stromal
      components. Both cell types could be considered a normal liver component in that
      wild fish population. A stereological study was performed to investigate eventual
      seasonality / breeding-related alterations in the amount (relative and total
      volumes) of EGCs and RCs. Differences only existed in the quantity of RCs;
      increasing from the earliest stages to the more advanced stages of ovarian
      maturation. EGCs made a greater pool than RCs only at early- and late
      vitellogenesis. Based on the breeding related fluctuations we suggest there is a
      hormonal regulation, by sex steroids, of the RCs liver content. Moreover, our
      data endorses the idea that, when using changes in the RCs pool as a biomarker,
      the fish breeding status must be considered as a potential source of changes in
      the RCs pool.

PMID- 17448687
TI  - Enhancement of nonspecific immunity and disease resistance in Oreochromis
      mossambicus by Solanum trilobatum leaf fractions.
AB  - The purpose of this study was to determine the effect of water and hexane soluble
      fractions of the Indian medicinal plant, Solanum trilobatum on the nonspecific
      immune mechanisms and disease resistance in Oreochromis mossambicus. Fish were
      intraperitoneally injected with different doses of 0, 4, 40 or 400 mg kg(-1) body
      weight of water or hexane soluble fraction. The nonspecific immune mechanisms
      were assessed in terms of serum lysozyme activity, reactive oxygen species
      production and reactive nitrogen species production by peripheral blood
      leucocytes. The functional immunity in terms of percentage mortality and Relative
      Percent Survival (RPS) was assessed by a challenge with live Aeromonas
      hydrophila. Almost all the doses of both water and hexane soluble fractions
      enhanced the serum lysozyme activity. All the doses of water soluble fraction
      significantly enhanced the ROS production on most of the days tested. In hexane
      soluble fraction treated groups, the enhancement in the ROS production was
      observed at least on 2 days. All the doses of water soluble fraction
      significantly enhanced the production of RNS only on one day. The RNS production
      was enhanced significantly only in the group treated with 40 mg kg(-1) of hexane
      fraction. The leaf fraction administration preceding the challenge with live A.
      hydrophila, decreased the percentage mortality in the experimental group with the
      consequent increase in RPS values. This preliminary study indicates that S.
      trilobatum could be used to promote the health status of fish in intensive
      finfish aquaculture.

PMID- 17448688
TI  - Dendritic spine detection using curvilinear structure detector and LDA
      classifier.
AB  - Dendritic spines are small, bulbous cellular compartments that carry synapses.
      Biologists have been studying the biochemical pathways by examining the
      morphological and statistical changes of the dendritic spines at the
      intracellular level. In this paper a novel approach is presented for automated
      detection of dendritic spines in neuron images. The dendritic spines are
      recognized as small objects of variable shape attached or detached to multiple
      dendritic backbones in the 2D projection of the image stack along the optical
      direction. We extend the curvilinear structure detector to extract the boundaries
      as well as the centerlines for the dendritic backbones and spines. We further
      build a classifier using Linear Discriminate Analysis (LDA) to classify the
      attached spines into valid and invalid types to improve the accuracy of the spine
      detection. We evaluate the proposed approach by comparing with the manual results
      in terms of backbone length, spine number, spine length, and spine density.

PMID- 17448690
TI  - Molecular insights indicate that Pachycara thermophilum () and P. saldanhai ()
      (Perciformes: Zoarcidae) from the Mid-Atlantic Ridge are synonymous species.

PMID- 17448689
TI  - Differentiation between external and internal cuing: an fMRI study comparing
      tracing with drawing.
AB  - Externally cued movement is thought to preferentially involve cerebellar and
      premotor circuits whereas internally generated movement recruits basal ganglia,
      pre-supplementary motor cortex (pre-SMA) and dorsolateral prefrontal cortex
      (DLPFC). Tracing and drawing are exemplar externally and internally guided
      actions and Parkinson's patients and cerebellar patients show deficits in
      tracking and drawing, respectively. In this study we aimed to examine this
      external/internal distinction in healthy subjects using functional imaging. Ten
      healthy subjects performed tracing and drawing of simple geometric shapes using
      pencil and paper while in a 3-T fMRI scanner. Results indicated that compared to
      tracing, drawing generated greater activation in the right cerebellar crus I,
      bilateral pre-SMA, right dorsal premotor cortex and right frontal eye field.
      Tracing did not recruit any additional activation compared to drawing except in
      striate and extrastriate visual areas. Therefore, drawing recruited areas more
      frequently associated with cognitively challenging tasks, attention and memory,
      but basal ganglia and cerebellar activity did not differentiate tracing from
      drawing in the hypothesised manner. As our paradigm was of a simple, repetitive
      and static design, these results suggest that the task familiarity and the
      temporal nature of visual feedback in tracking tasks, compared to tracing, may be
      important contributing factors towards the degree of cerebellar involvement.
      Future studies comparing dynamic with static external cues and visual feedback
      may clarify the role of the cerebellum and basal ganglia in the visual guidance
      of drawing actions.

PMID- 17448691
TI  - The introduction of an extracellular matrix-based scaffold to the marketplace.
AB  - Continuous application of new scientific knowledge is a central characteristic of
      modern medical practice. The current pace of medical innovation creates an
      environment of rapid change, and the introduction of innovative treatments in the
      area of regenerative medicine in orthopaedics prompts health care providers,
      medical device companies, patient advocacy groups, and health insurance payors to
      study the most optimal method for introducing these treatments to clinical
      practice. Questions regarding the role and value of preclinical testing, clinical
      trials, and postmarketing surveillance are pertinent to this discussion, and
      answers to these questions should culminate in a strategy that benefits patient
      care.

PMID- 17448692
TI  - Apparently isolated partial articular fractures of the radial head: prevalence
      and reliability of radiographically diagnosed displacement.
AB  - The purpose of this study was to measure the prevalence and reliability of the
      radiographic diagnosis of displacement of apparently isolated partial articular
      radial head fractures and use these factors to assess treatment considerations.
      Among 119 radiographically visible partial fractures of the radial head not
      associated with other wrist, forearm, or elbow injury, 101 were classified as
      Mason type 1 (85%), 11 as borderline between Mason type 1 and Mason type 2
      fractures (9%), and 7 as Mason type 2 fractures (6%) according to Broberg and
      Morrey's modification of the Mason classification. The intraobserver reliability
      of the classification of Mason type 1 and type 2 fractures was excellent (mean
      kappa, 0.85), but the interobserver reliability was only moderate (multirater
      kappa, 0.45). Because apparently isolated, stable partial fractures of the radial
      head are infrequently displaced and observers have moderate disagreement
      regarding the diagnosis of displacement, it is likely that displacement is
      overdiagnosed.

PMID- 17448693
TI  - Elbow dislocation translocation in a child: a case report.

PMID- 17448694
TI  - Imaging of the rotator cuff following repair: human and animal models.
AB  - Imaging of the rotator cuff following repair may be challenging due to the type
      of fixation, surgical manipulation of the tissue and the presence of residual
      defects that may exist in the presence of good functional outcome. Both
      ultrasound and magnetic resonance (MR) imaging present unique advantages in
      evaluation of the postoperative tissue. MR imaging has superior soft tissue
      contrast and provides a more global shoulder assessment, including the degree of
      arthrosis, while ultrasound enables a more dynamic testing of the repaired
      tissue. Power Doppler ultrasound and new contrast agents provide insight into the
      degree of vascular recruitment following repair.

PMID- 17448695
TI  - Shoulder arthroplasty: the socket perspective.
AB  - Although much attention has been directed to the development of the humeral
      components used in shoulder arthroplasty, the major unsolved challenge lies on
      the glenoid side of the articulation. This challenge arises from difficulties
      resisting eccentric loading and providing adequate implant-bone fixation. Current
      glenoid component designs use polyethylene and polymethyl methacrylate and are
      prone to loosening, plastic deformation, particulate debris, and third-body wear.
      Metal-backed components present further challenges, and results have generally
      been disappointing. There is interest in biologic resurfacing procedures,
      including the interposition of fascia, capsule, or meniscal allograft and
      nonprosthetic glenoid arthroplasty, or what has become known as the "ream-and
      run" procedure. Despite encouraging results, important questions remain
      unanswered about these procedures. However, each may warrant further exploration
      with a goal of providing an effective and durable approach to glenoid arthritis
      that avoids the risks associated with polymethyl methacrylate and polyethylene.

PMID- 17448696
TI  - Arthroscopic versus open distal clavicle excision: comparative results at six
      months and one year from a randomized, prospective clinical trial.
AB  - The purpose of this report is to compare outcomes after arthroscopic versus open
      distal clavicle excision in the treatment of refractory acromioclavicular joint
      pain. A randomized, prospective clinical trial comparing the 6-month and 1-year
      outcomes of patients undergoing open distal clavicle excision (group 1) with
      those undergoing arthroscopic distal clavicle excision (group 2) was carried out.
      The Modified American Shoulder and Elbow Surgeons form, visual analog scale pain
      score, Short Form 36, and satisfaction questions were assessed preoperatively and
      at 6 months and 1 year postoperatively. Seventeen patients were enrolled. There
      was a trend across all measures for earlier or better outcomes (or both) after
      arthroscopic over open treatment. The improvement in visual analog scale pain
      score from preoperatively to 1 year postoperatively was significant for group 2
      but not group 1 (P = .006 vs P = .13). Occult intra-articular pathology was
      detected and treated in 50% of group 2 patients. Arthroscopic and open distal
      clavicle excisions both provide significant pain reduction at 1 year. Both are
      effective surgeries for the treatment of refractory acromioclavicular joint pain.
      The ability to diagnosis and treat subtle concomitant shoulder pathology is a
      unique advantage of the arthroscopic approach.

PMID- 17448697
TI  - Acute deep infection after surgical fixation of proximal humeral fractures.
AB  - Acute deep infection after open reduction-internal fixation of proximal humeral
      fractures is uncommon. Currently, there are no reported series on the outcomes of
      patients treated for infection after surgery for proximal humeral fractures. The
      purpose of this study was to review the frequency, clinical presentation,
      bacteriology, treatment, and outcomes of patients with such fractures complicated
      by acute deep infection. Between 1993 and 2003, 5 patients with acute deep
      infection after open reduction-internal fixation of proximal humeral fractures
      were identified. The medical records, laboratory data, and radiographs were
      examined retrospectively. The mean age at the time of infection diagnosis was 50
      years (range, 33-82 years), and the mean interval from proximal humeral fracture
      fixation to the time of infection diagnosis was 27 days (range, 14-40 days). All
      patients were available for final follow-up evaluation at a mean of 6.4 years
      (range, 32 months to 8.3 years). Of the 5 patients, 4 (80%) went on to nonunion
      requiring revision surgery. Coagulase-negative Staphylococcus species and
      Propionibacterium acnes were the most common organisms isolated. A mean of 3.3
      surgical debridements were necessary for the eradication of infection. At a mean
      final follow-up of 6.4 years, the American Shoulder and Elbow Surgeons score
      averaged 53 points (range, 33-75 points) and the Simple Shoulder Test score
      averaged 6.2 points (range, 1-10 points). Acute deep infection after open
      reduction-internal fixation of proximal humeral fractures is a devastating
      complication. Patients should be counseled that the results of treatment of deep
      infection are plagued with high complication rates, poor functional outcome, and
      a notably high nonunion rate.

PMID- 17448698
TI  - The types and severity of complications associated with interscalene brachial
      plexus block anesthesia: local and national evidence.
AB  - Interscalene brachial plexus block is a commonly used anesthetic. However,
      substantial complications can be associated with its use. Our study included 15
      years of data from a local medical center and 3 decades of records from the
      national American Society of Anesthesiology Closed Claims Project. The hospital
      had 27 peripheral neurologic injuries, 3 central nervous system complications, 6
      respiratory complications, and 5 cardiovascular complications. Of these
      complications, 14 were still present at the most recent follow-up, some causing
      major compromise of the patient's comfort and function. All central blocks, local
      toxicities, and respiratory complications resolved. In the hospital series, more
      experienced anesthesiologists tended to have lower complication rates. The
      American Society of Anesthesiology Closed Claims database had 20 peripheral
      neurologic injuries, 10 respiratory complications, 5 central nervous system
      complications, 4 deaths, 2 emotional disturbances, and 1 other unknown event. Of
      the complications, 19 were described as permanent. Interscalene brachial plexus
      block can be accompanied by substantial and disabling complications, especially
      when administered by less experienced anesthesiologists.

PMID- 17448699
TI  - Tendon and bone responses to a collagen-coated suture material.
AB  - Tendon to bone integration after rotator cuff repair is not a reproducible
      process. During repair, bioabsorbable and nonabsorbable suture material is
      universally used to facilitate the procedure. Improving the biological
      architecture of inert suture might aid in overall tendon to bone healing. The
      objective of our study is to enhance the bone to tendon union by absorbing type I
      collagen onto high strength nonabsorbable polyester/polyethylene suture commonly
      used in rotator cuff surgery. Our purpose was to evaluate the tendon and bone
      cellular response to this novel coated suture compared to uncoated suture.
      Primary human osteoblasts (HOBs) and tenocytes were plated onto
      polyester/polyethylene suture that was either uncoated or coated with type I
      bovine collagen. Cell adhesion to the sutures was assayed at 24 hours.
      Proliferation was determined at 48 hours by measuring [3H]- Thymidine
      incorporation in cells attached to the sutures. At 24 and 48 hours, respectively,
      cells grown on the collagen-coated suture showed a significantly greater response
      measured by adhesion and proliferation than cells grown on uncoated suture. At
      five days of culture, alkaline phosphatase activity and protein synthesis was
      significantly greater on the collagen-coated suture compared to uncoated.
      Collagen-coated polyester/polyethylene suture appears to stimulate adhesion,
      proliferation alkaline phosphatase, and protein synthesis more than uncoated
      sutures, and therefore may aid in the tendon to bone incorporation process
      critical to rotator cuff repair.

PMID- 17448700
TI  - The efficacy, safety and carry-over effect of diacerein in the treatment of
      painful knee osteoarthritis: a randomised, double-blind, NSAID-controlled study.
AB  - OBJECTIVE: To evaluate the efficacy, safety and carry-over effect of diacerein,
      in comparison to piroxicam, in the treatment of Thai patients with symptomatic
      knee osteoarthritis (OA). DESIGN: This was a double-blind, randomised, piroxicam
      controlled, parallel-group study. A 7-day non-steroidal anti-inflammatory drug
      washout period was followed by a 16-week treatment period with either diacerein
      100mg/day or piroxicam 20mg/day, and an 8-week treatment-free observation period.
      The primary efficacy criterion was pain on Western Ontario and McMaster
      University Osteoarthritis (WOMAC) A. The secondary criteria included WOMAC B, C
      and total WOMAC, paracetamol intake, Short Form-36 questionnaire and global
      judgements on efficacy and tolerability by patients and investigators. RESULTS:
      Of 171 randomised patients, 150 completed the study and 161 were analysed in the
      intent-to-treat population (diacerein: 82, piroxicam: 79). Pain (WOMAC A)
      decreased to a similar extent in both groups at Week 16 (diacerein: -69.7%+/
      31.5%; piroxicam: -74.1+/-26.2%; P=n.s.). On treatment discontinuation, pain
      increased in the piroxicam group at Weeks 20 (-47%+/-47.8%) and 24 (-26.8%+/
      60.6%) while improvements persisted in the diacerein group at Weeks 20 (-66.9%+/
      35.9%) and 24 (-69.5%+/-33.7%), with a significant difference in favour of
      diacerein at Weeks 20 and 24, demonstrating the carry-over effects of the drug.
      The incidence of adverse events was similar in both groups but more patients from
      the piroxicam group dropped out of the study due to these events. CONCLUSIONS:
      Diacerein was as effective as piroxicam in reducing pain and improving function
      but, unlike piroxicam, displayed a carry-over effect and a better safety profile.

PMID- 17448701
TI  - Differences between systematic reviews/meta-analyses of hyaluronic
      acid/hyaluronan/hylan in osteoarthritis of the knee.
AB  - OBJECTIVE: To explore reasons for discrepant results between systematic reviews
      (SR)/meta-analyses (MA) of the efficacy and safety of hyaluronic
      acid/hyaluronan/hylan (HA) therapy in the treatment of osteoarthritis (OA) of the
      knee. METHODS: A decision algorithm was utilised to identify reasons for
      discordance among six SR. Sources of discordance such as clinical question, trial
      selection and inclusion, data extraction, assessment of study quality, assessment
      of the ability to combine trials, and statistical methods for data synthesis were
      examined. RESULTS: A similar question was asked in all six SR. Different trials
      were selected for inclusion in the reviews mainly because of differences in the
      search strategies and selection criteria. Although similar methods for data
      extraction were utilised, differences were found both in the outcome measures and
      time-points selected for extraction. Methodological quality was not always
      formally assessed. Different statistical methods for data synthesis resulted in
      conflicting estimates of therapeutic effect. CONCLUSIONS: Reasons for the
      inconsistency of results reported in the six SR were identified. Using the
      principles of the GRADE approach for estimating the therapeutic effect of HA in
      the treatment of OA of the knee, there is moderate evidence suggesting that
      further research is unlikely to change our confidence in the estimate of the
      effect. In the balance of benefit to harm, the trade-off is probable benefit with
      respect to pain reduction and physical function improvement with low risk of
      harm.

PMID- 17448702
TI  - Interleukin-1 and tumor necrosis factor alpha inhibit repair of the porcine
      meniscus in vitro.
AB  - OBJECTIVE: Injury or removal of the knee meniscus leads to progressive joint
      degeneration, and current surgical therapies for meniscal tears seek to maximally
      preserve meniscal structure and function. However, the factors that influence
      intrinsic repair of the meniscus are not well understood. The goal of this study
      was to investigate the capacity of meniscus tissue to repair a simulated defect
      in vitro and to examine the effect of pro-inflammatory cytokines on this process.
      METHODS: Cylindrical explants were harvested from the outer one-third of medial
      porcine menisci. To simulate a full-thickness defect, a central core was removed
      and reinserted immediately into the defect. Explants were cultured for 2, 4, or 6
      weeks in serum-containing media in the presence or absence of interleukin-1 (IL
      1) or tumor necrosis factor alpha (TNF-alpha), and meniscal repair was
      investigated using mechanical testing and fluorescence confocal microscopy.
      RESULTS: Meniscal lesions in untreated samples showed a significant capacity for
      intrinsic repair in vitro, with increasing cell accumulation and repair strength
      over time in culture. In the presence of IL-1 or TNF-alpha, no repair was
      observed despite the presence of abundant viable cells. CONCLUSIONS: This study
      demonstrates that the meniscus exhibits an intrinsic repair response in vitro.
      However, the presence of pro-inflammatory cytokines completely inhibited repair.
      These findings suggest that increased levels of pro-inflammatory cytokines post
      injury or under arthritic conditions may inhibit meniscal repair. Therefore,
      inhibition of these cytokines may provide a means of accelerating repair of
      damaged or injured menisci in vivo.

PMID- 17448703
TI  - Time-courses of Fos expression in rat hippocampus and neocortex following
      acquisition and recall of a socially transmitted food preference.
AB  - The present study examined expression of the immediate-early gene, c-Fos,
      following acquisition, 48-h (recent) recall, and 1-week (remote) recall of a
      socially transmitted food preference (STFP) in multiple brain regions implicated
      in learning and memory. In comparisons with controls, trained Long-Evans rats had
      increased Fos immunoreactivity in the ventral hippocampus following acquisition
      and recent recall. In the parahippocampal cortices, Fos was increased in the
      lateral entorhinal cortex after acquisition. In the orbitofrontal cortex,
      increased Fos immunoreactivity was observed in the lateral orbital cortex
      following both recent and remote recall and in the ventral orbital cortex
      following remote recall, indicating a role for the orbitofrontal cortex in the
      remote recall of STFP memory. In contrast, in the medial prefrontal cortex,
      increased Fos-ir was found following acquisition in the prelimbic cortex and
      following recent recall in the prelimbic and infralimbic cortices. No differences
      in Fos expression were found between trained rats and controls in the dorsal
      hippocampus, posterior parietal cortex, or amygdala. The present findings support
      a time-limited role of the hippocampus in the acquisition and recall of STFP
      memory and implicate neocortical regions involved in STFP acquisition, recent,
      and remote recall.

PMID- 17448704
TI  - Effects of image artifacts on gray-value density in limited-volume cone-beam
      computerized tomography.
AB  - OBJECTIVE: An in vitro study was designed to investigate the influence of
      projection data discontinuity-related artifacts in limited-volume cone-beam
      computerized tomography (CBCT) imaging of the jaws. STUDY DESIGN: Test objects
      were positioned in 4 patterns in a water-filled phantom as follows: bimandible
      and vertebrae, bimandible, left mandible and vertebrae, and left mandible. The CT
      imaging of the left molar region was performed using image intensifier (II)- and
      flat panel detector (FPD)-based CBCT scanners. The CT value of the mandible and
      the adjacent soft tissue region were analyzed for density by means of an 8-bit
      grayscale. RESULTS: The effects of artifacts were scored as the difference in
      relative density between the lingual and buccal soft tissue. The intensity of
      artifacts increased when more objects were presented outside the area being
      imaged. Fewer artifacts were noted in images produced by the particular FPD CBCT
      used in this investigation. CONCLUSION: The CBCT system using an FPD resulted in
      fewer artifacts than the CBCT system using an II in this particular study.

PMID- 17448705
TI  - Comparison between true and partial hemifacial hypertrophy.
AB  - Hemifacial hypertrophy (HFH) is rare and characterized by unilateral enlargement
      of the head and teeth. Hemifacial hypertrophy is classified as true HFH (THFH)
      with unilateral enlargement of the viscerocranium, and partial HFH (PHFH) in
      which not all structures are enlarged. We present a case of THFH and compare and
      contrast it with a case of PHFH. Hemifacial hypertrophy may cover a wide spectrum
      of defects or may involve only muscle or bone. Myohyperplasia, reported
      previously as a separate syndrome, may actually represent a forme fruste of PHFH
      or THFH. The PHFH patient lead a healthy, normal life without significant
      psychosocial problems and was reluctant to accept his deformity. Contrastingly,
      the THFH patient had significant social stigma and compromised health together
      with major aesthetic morbidity. Treatment planning in THFH is arduous and
      involves multiple modalities. Therefore, it is imperative to differentiate THFH
      and PHFH for better understanding and management of the condition.

PMID- 17448706
TI  - Histopathologic study of physiological and pathological resorptions in human
      primary teeth.
AB  - This study presents a histological analysis through optical microscopy of primary
      teeth with physiological and pathological resorptions to outline the histological
      profile of resorptions. Sixty teeth were examined: 19 primary teeth with
      physiological resorption and 41 primary teeth with pathological resorption. To
      analyze the histological conditions of the pulp, periradicular tissue, and the
      resorption areas, and to investigate the presence, intensity, and location of
      bacteria, slides were prepared using the hematoxylin-eosin and the Brown-Brenn
      techniques. For the teeth with physiological resorption, normal pulps and no
      evidence of bacteria were found. For the teeth with pathological resorption,
      pulpal alterations, atypical resorption, and bacteria were observed.

PMID- 17448707
TI  - Review of flap design influence on the health of the periodontium after
      mandibular third molar surgery.
AB  - The purpose of this study is to review the effect of flap design in terms of
      periodontal status of the preceding second molar after lower third molar surgery.
      Impacted lower third molar surgery may result in periodontal complications on the
      distal surface of the adjacent second molar. Flap design that is used during
      impacted third molar surgery is important to prevent those complications. Several
      different flap techniques, mainly envelope, triangular (vertical) flaps, and
      their modifications have been developed to minimize those complications. Each
      technique has some advantages as well as disadvantages. It is also reported that
      the selection of a flap design does not seem to have a lasting effect on the
      health of periodontal tissue. The effect of the type of flap used for lower third
      molar surgery on the periodontal status of the second molar, as well as the
      factors that may influence this outcome, has been uncertain. The decision to use
      on one or the other of the flaps should be based on surgeon's preference.

PMID- 17448708
TI  - A comparison of lower lip hypoesthesia measured by trigeminal somatosensory
      evoked potential between different types of mandibular osteotomies and fixation.
AB  - PURPOSE: The purpose of this study was to compare objectively, the recovery of
      hypoestheia of the lower lip following orthognathic surgery using different
      procedures (sagittal split ramus osteotomy [SSRO]) and intra-oral vertical ramus
      osteotomy (IVRO)) and fixation methods (monocortical plate fixation and bi
      cortical plate fixation). Hypoesthesia was evaluated using the trigeminal
      somatosensory-evoked potential (TSEP). PATIENTS AND METHODS: The subjects
      consisted of 174 patients (348 sides) with mandibular prognathism with or without
      asymmetry, who underwent mandibular ramus osteotomies using different fixation
      types. The patients were divided into 4 groups. The OAM group consisted of 128
      sides who had SSRO using the Obwegeser method with mono-cortical absorbable plate
      fixation, the ODTM group consisted of 84 sides who had the Obwegeser-Dal Pont
      method with mono-cortical titanium plate fixation, the OTB group consisted of 32
      sides who had the Obwegeser method with bi-cortical titanium plate fixation and
      the VO group consisted of 104 sides who underwent IVRO according to the Bell
      method without fixation. Trigeminal nerve hypoestheia at the region of the lower
      lip was assessed bilaterally by the TSEP method. An electroencephalograph
      recording system (Neuropack Sigma; Nion Koden Corp., Tokyo, Japan) was used to
      analyze the potentials. Each patient was evaluated pre-operatively and then post
      operatively at 1 and 2 weeks, 1, 3, and 6 months, and 1 year. RESULTS: The mean
      measurable period and standard deviation of TSEP of the lower lip in the OAM
      group was 5.2 +/- 9.9 weeks, 10.9 +/- 13.1 weeks in the ODTM group, 7.8 +/- 4.5
      weeks in the OTB group, and 2.5 +/- 6.3 weeks in the VO group. There were
      significant differences between the OAM and ODTM groups (P < .0001), the ODTM and
      OTB groups (P = .0001), the OTB and VO groups (P = .0221), the OAM and VO groups
      (P < .0001), and the ODTM and VO groups (P < .0001). CONCLUSION: This study
      proved using objective measurements that the recovery period from hypoesthesia of
      the lower lip following orthognathic surgery was dependent on the surgical
      procedure. Recovery in lower lip hypoesthesia after IVRO was significantly
      earlier than SSRO.

PMID- 17448709
TI  - Bisphosphonates and osteonecrosis of the jaws: science and rationale.
AB  - Bisphosphonates as a group of drugs were introduced for the management of various
      conditions such as osteoporosis, Paget's disease, multiple myeloma, hypercalcemia
      of malignancy, breast cancer, prostate cancer, and other tumors. This group of
      drugs has improved the quality of life in many patients with proven efficacy in
      limiting pain and skeletal-related events. The controversy of osteonecrosis of
      the jaws and bisphosphonates is a recent and growing problem. Osteonecrosis of
      the jaws is recognized as a serious complication of bisphosphonate therapy, more
      commonly with the intravenous form of the drugs. However, there is limited
      scientific understanding about the association between osteonecrosis of the jaws
      and bisphosphonates. In the present article we discuss various mechanisms of
      action of bisphosphonates, the rationale for occurrence of osteonecrosis in the
      jaws, and treatment guidelines for the condition.

PMID- 17448710
TI  - Ameloblastic carcinoma: an analysis of 14 cases.
AB  - OBJECTIVES: To present the classifications of malignant ameloblastomas, provide
      histopathologic guidelines for the diagnosis of ameloblastic carcinoma, and
      discuss treatment and long-term follow-up. STUDY DESIGN: Fourteen archival
      specimens of ameloblastic carcinoma with detailed treatment and follow-up
      documentation were identified by the authors. RESULTS: Traditional methods of
      microscopic observation form the basis for diagnosis. Histopathologic features of
      ameloblastic carcinoma include lack of differentiation, hypercellularity, high
      mitotic index, vascular invasion, and neural invasion. CONCLUSION: The long-term
      follow-up findings in this study support the concept that aggressive surgical
      intervention provides the best chance for survival. Patients treated otherwise
      had recurrence. The patients with the highest number of recurrences did not
      survive the disease.

PMID- 17448711
TI  - Relationship between bite force and salivary flow in older adults.
AB  - OBJECTIVE: To examine the relationship between bite force and stimulated salivary
      flow rate in older adults. STUDY DESIGN: The study sample consisted of 934
      independent-living, cognitively healthy Japanese older adults 60 to 84 years of
      age. The maximal bite force was measured with pressure-sensitive sheets, and
      stimulated whole saliva was collected using the mastication method. RESULTS: The
      mean stimulated salivary flow rate was 1.36 +/- 0.97 mL/min. In bivariate
      analysis, the stimulated salivary flow rate was significantly lower in females
      and subjects with daily multiple medications (P < .01). Multiple linear
      regression analysis showed that the stimulated salivary flow rate was
      significantly associated with sex (standardized partial regression coefficient:
      partial beta = .22; P < .001), bite force (partial beta = .18; P < .001), and
      multiple daily medications (partial beta = -.12; P < .001). CONCLUSIONS: It is
      suggested that reduced bite force is associated with a decline in stimulated
      whole salivary flow rate independent of sex and medication in older adults.

PMID- 17448712
TI  - Evaluation of a survey approach to estimating the prevalence of cattle carrying
      antimicrobial-resistant Escherichia coli.
AB  - A random survey of farms in the Highlands and Islands of Scotland provides
      estimated of the prevalence of calves, finishers and cows carrying ampicillin,
      apramycin and/or nalidixic acid resistant Escherichia coli. While the survey
      provides information on the geographical variation in risk, the results are of
      limited value for interpreting causality.

PMID- 17448713
TI  - matNMR: a flexible toolbox for processing, analyzing and visualizing magnetic
      resonance data in Matlab.
AB  - matNMR (matnmr.sourceforge.net) is a toolbox for processing, analyzing and
      visualizing magnetic-resonance data within the Matlab environment
      (www.mathworks.com) that aims for control, flexibility and extendability.
      Processing can be done using either a graphical user interface or with command
      line scripts, both of which allow user-defined processing or analysis functions
      to be incorporated at any time. The direct access to data points during
      processing, and the extensive library of mathematical and visualization routines
      provided by Matlab, afford the high degree of control and flexibility needed in
      modern magnetic-resonance research.

PMID- 17448714
TI  - Signal enhancement in CRAZED experiments.
AB  - Many of the promising applications of the CRAZED (COSY Revamped with Asymmetric Z
      gradient Echo Detection) experiments are in biomedical and clinical technologies.
      In tissue, however, signal from the typical CRAZED experiment is largely limited
      by transverse relaxation. When relaxation is included, the maximum achievable
      signal from a prototypical CRAZED sequence, in the linear regime, is proportional
      to T(2)/tau(d). This means that for samples with a short T(2), as encountered in
      vivo, signals from intermolecular multiple-quantum coherences (iMQCs) reach very
      diminished signal intensities. While relaxation is generally regarded as a
      fundamental constraint, we show here that when T(2) is short but T(1) is long, as
      in tissue, there are simple sequence modifications that can increase signal
      beyond the T(2) limit. To better utilize the available signal intensity from
      iMQCs we propose a method to substitute part of the transverse magnetization with
      the longitudinally modulated magnetization. In this paper we show, with both
      simulations and experimental results, that in the presence of strong transverse
      relaxation the standard CRAZED scheme is not the optimal method for observing
      iMQCs, and can be improved upon with simple modifications.

PMID- 17448715
TI  - A novel low-E field coil to minimize heating of biological samples in solid-state
      multinuclear NMR experiments.
AB  - A novel coil, called Z coil, is presented. Its function is to reduce the strong
      thermal effects produced by rf heating at high frequencies. The results obtained
      at 500MHz in a 50 microl sample prove that the Z coil can cope with salt
      concentrations that are one order of magnitude higher than in traditional
      solenoidal coils. The evaluation of the rf field is performed by numerical
      analysis based on first principles and by carrying out rf field measurements.
      Reduction of rf heating is probed with a DMPC/DHPC membrane prepared in buffers
      of increasing salt concentrations. The intricate correlation that exists between
      the magnetic and electric field is presented. It is demonstrated that, in a
      multiply tuned traditional MAS coil, the rf electric field E(1) cannot be reduced
      without altering the rf magnetic field. Since the detailed distribution differs
      when changing the coil geometry, a comparison involving the following three
      distinct designs is discussed: (1) a regular coil of 5.5 turns, (2) a variable
      pitch coil with the same number of turns, (3) the new Z coil structure. For each
      of these coils loaded with samples of different salt concentrations, the nutation
      fields obtained at a certain power level provide a basis to discuss the impact of
      the dielectric and conductive losses on the rf efficiency.

PMID- 17448716
TI  - Estimation and measurement of flat or solenoidal coil inductance for
      radiofrequency NMR coil design.
AB  - The inductance of a radiofrequency coil determines its compatibility with a given
      NMR probe circuit. However, calculation (or estimation) of inductance for
      radiofrequency coils of dimensions suitable for use in an NMR probe is not
      trivial, particularly for flat-coils. A comparison of a number of formulae for
      calculation of inductance is presented through the use of a straightforward
      inductance measurement circuit. This technique relies upon instrumentation
      available in many NMR laboratories rather than upon more expensive and
      specialized instrumentation often utilized in the literature. Inductance
      estimation methods are suggested and validated for both flat-coils and solenoids.
      These have proven very useful for fabrication of a number of new coils in our
      laboratory for use in static solid-state NMR probes operating at (1)H frequencies
      of 300 and 600MHz. Solenoidal coils with very similar measured and estimated
      inductances having inner diameters from 1 to 5mm are directly compared as an
      example of the practical application of inductance estimation for interchange of
      coils within an existing solid-state NMR probe.

PMID- 17448717
TI  - Dynamics of biochemical components, lipid classes and energy values on gonadal
      development of R. philippinarum associated with the temperature and ingestion
      rate.
AB  - This study evaluates the effect of temperature, coupled with ingestion rate, on
      the dynamics of biochemical components and lipid classes in R. philippinarum. The
      data are discussed with regard to sexual development and energy balance.
      Experimental protocol developed in the present study used two groups of the clam
      R. philippinarum: L (temperatures of 14 degrees C and 18 degrees C) and H
      (temperatures of 18 degrees C and 22 degrees C). The intra-group ingestion level
      was similar, although the ingestion level of the clams in the group H was 2.4
      times higher than group L. We observed that R. philippinarum conditioned at 18
      degrees C (18L) shows higher protein content, furthermore an important loss of
      organic weight was observed after 48 days. In such a situation, the clams use
      their own reserves (carbohydrates and glycogen) for sexual development while in
      situations without food stress (positive energy balance) and low temperature (14
      degrees C) an accumulation of reserves is produced. Strikingly dissimilar
      behaviour in biochemical composition was observed for the 18H and 22H treatments,
      both with a positive energy balance. Despite similar protein content, the highest
      levels of carbohydrates were observed at the lower temperature (18 degrees C).
      Glycogen was also higher for the 18 degrees C treatment, although the differences
      were significant only in the males. Although the total lipids in R. philippinarum
      showed no significant differences in any treatment, they became apparent and
      related to sex when considering the individual lipid classes. There was no
      variation in lipid classes in the males between the 14L and 22H treatments
      despite the large disparity in the degree of sexual development. However, in the
      females significant differences in lipid classes (phospholipids, triglycerides)
      were observed. The results of this study show that a positive energy balance
      permits R. philippinarum gonadal development and accumulation of reserves both in
      low and high temperature conditions. In low temperature situations, gonadal
      development is slower and the energy reserves are accumulated in the form of
      carbohydrates. When the clams are conditioned at high temperatures, gonadal
      development is fast and complete, carbohydrates are consumed and lipids are
      accumulated.

PMID- 17448718
TI  - Using haematological parameters to infer the health and nutritional status of an
      endangered black-necked swan population.
AB  - Living organisms are continuously faced with several forms of environmental
      perturbation, one of the most important being human activity. In this scenario,
      the role of physiological studies on wildlife has proved to be important given
      that in vivo physiological variables reflect a great deal how sensitive animals
      are to acute environmental changes. We studied the haematological parameters in
      black-necked swans (Cygnus melanocoryphus) at the Ramsar site at the Carlos
      Anwandter Sanctuary, which were experiencing a drastic population decrease.
      Through seven months, body mass (body mass corrected by total length) was reduced
      30%, which was followed by significant reductions of haemoglobin concentration,
      haematocrit and red blood cell count. Mean cell volume and mean cell haemoglobin
      concentration did not change with time, whereas there was a significant increase
      of the white blood cells and heterophile / lymphocyte ratio. Our results,
      together with the published evidence, suggests that the proximal factors
      associated with the mass mortality and emigration of the black - necked swan
      population at the "Carlos Anwandter Sanctuary" was a drastic nutritional
      deficiency, and the potentially toxic effects of iron pollution in the waters of
      the Ramsar site.

PMID- 17448719
TI  - Physiologically inspired signal preprocessing for auditory prostheses: insights
      from the electro-motility of the OHC.
AB  - We designed a non-linear functional model of the outer hair cell (OHC)
      functioning in the filtering system of the cochlea and then isolated from it two
      second-order structures, one employing the mechanism of the somatic motility and
      the other the hair bundle motion of the OHC. The investigation of these circuits
      showed that the main mechanism increasing the sensitivity and frequency
      selectivity of the filtering system is the somatic motility. The mechanism of the
      active hair bundle motion appeared less suitable for realization of the band-pass
      filtering structures due to the dependence of the sensitivity, natural frequency
      and selectivity on the signal intensity. We combined three second-order filtering
      structures employing the mechanism of the somatic motility and the lateral
      inhibition to form a parallel-type filtering channel of the sixth order with the
      frequency characteristics of the Butterworth-type and Gaussian-type. The
      investigation of these channels showed that the Gaussian-type channel has the
      advantage over the Butterworth-type channel. It is more suitable for realization
      of a filter bank with common lateral circuits and has less distorted frequency
      characteristic in the nonlinear mode.

PMID- 17448720
TI  - CSF biomarker profiles do not differentiate between the cerebellar and
      parkinsonian phenotypes of multiple system atrophy.
AB  - BACKGROUND: Multiple system atrophy (MSA) can clinically be divided into the
      cerebellar (MSA-C) and the parkinsonian (MSA-P) variants. It is unknown whether
      the variation in clinical expression is also reflected by a different underlying
      neurochemical profile. METHODS: We analyzed brain specific proteins and
      neurotransmitter metabolites in cerebrospinal fluid (CSF) of 26 patients with MSA
      C and 19 with MSA-P. RESULTS: No differences were found between MSA-C and MSA-P.
      CONCLUSION: Our results suggest that the clinical and in part pathological
      distinction between the two clinical MSA phenotypes is not reflected by the
      neurochemical composition of CSF.

PMID- 17448721
TI  - Relatively spared mesocorticolimbic dopaminergic system in juvenile parkinsonism.
AB  - This study aims to examine the function of the mesocorticolimbic dopaminergic
      system, including the amygdala, in recognizing emotions in juvenile parkinsonism
      (JP). Eleven patients with JP and 16 age-matched controls selected one basic
      emotion (happiness, sadness, anger, fear, surprise, or disgust) that best
      described the emotional state represented by visual and auditory stimuli. There
      was no significant difference between the patients and normal controls in their
      recognition of emotions. The spared emotion recognition in JP could be attributed
      to the absence of any pathological changes or the normal dopamine concentrations
      in the mesocorticolimbic system in this condition.

PMID- 17448722
TI  - alpha1-Antitrypsin regulates CD14 expression and soluble CD14 levels in human
      monocytes in vitro.
AB  - The recognition of bacterial lipopolysaccharide (LPS) is principally mediated by
      either membrane-bound or soluble form of the glycoprotein CD14 and CD14
      associated signal transducer, toll-like receptor 4 (TLR4). Recent findings
      indicate that the serine protease inhibitor, alpha1-antitrypsin (AAT), may not
      only afford protection against proteolytic injury, but may also neutralize
      microbial activities and affect regulation of innate immunity. We postulated that
      AAT affects monocyte responses to LPS by regulating CD14 expression and soluble
      CD14 release. Here we show that a short-term (up to 2h) monocyte exposure to AAT
      alone or in combination with LPS leads to a remarkable induction of CD14 levels.
      In parallel, a short-term (2h) cell exposure to AAT/LPS significantly enhances
      LPS-induced NF kappaB (p50 and p65) activation in conjunction with increased
      TNFalpha, IL-1 beta and IL-8 release. In contrast, longer term incubation (18 h)
      of monocytes with combined AAT/LPS results in a significant reduction in
      expression of both CD14 and TLR4, inhibition of LPS-induced TNFalpha, IL-1 beta
      and IL-8 mRNA and protein expression. These findings provide evidence that AAT is
      an important regulator of CD14 expression and release in monocytes and suggest
      that AAT may be involved in LPS neutralization and prevention of over-activation
      of monocytes in vivo.

PMID- 17448723
TI  - Pronounced improvement in systolic and diastolic ventricular long axis function
      after treatment with metoprolol.
AB  - BACKGROUND: Although it is well known that left ventricular (LV) function
      improves after treatment with beta-blockers in heart failure, little attention
      has been paid to the effects on LV long axis (LAX) function. AIMS: To evaluate LV
      LAX function after treatment with metoprolol, and to assess whether LV LAX
      contractile reserve could predict future long-term improvement. METHODS: Twenty
      four heart failure patients were randomised to metoprolol or placebo for 6
      months, followed by 6 months of open treatment with metoprolol. Rest and
      dobutamine stress echocardiography (DSE) was performed before and after each
      treatment period. RESULTS: After treatment with metoprolol, LV LAX function
      improved significantly, systolic velocity from 29+/-8 to 32+/-15 mm/s, p<0.01
      (metoprolol) vs. 28+/-7 to 28+/-11 mm/s, ns (placebo); atrioventricular plane
      fractional shortening (AVP-FS) from 5.4+/-2.1 to 7.4+/-2.7%, p<0.001 (metoprolol)
      vs. 5.9+/-2.1 to 5.8+/-2.9%, ns (placebo). The improvement in function was
      maintained during DSE. LV LAX contractile reserve could not predict treatment
      response; the treatment effect on LV LAX function was significantly greater than
      the contractile reserve at baseline. The relative improvement in LV LAX function
      after metoprolol was 38%, compared with a 20% improvement in LV ejection fraction
      (EF). CONCLUSION: A significant improvement in LV LAX function was observed after
      treatment with metoprolol. AVP-FS and systolic velocities increased
      significantly, and to a greater extent than LVEF.

PMID- 17448724
TI  - Tumor-specific colonization, tissue distribution, and gene induction by probiotic
      Escherichia coli Nissle 1917 in live mice.
AB  - Systemic administration of microorganisms into tumor-bearing mice revealed
      preferential accumulation in tumors in comparison to clearance in organs such as
      spleen and liver. Here we compared the efficiency of tumor-specific colonization
      of pathogenic Salmonella typhimurium strains 14028 and SL1344 to the
      enteroinvasive Escherichia coli 4608-58 strain and to the attenuated Salmonella
      flexneri 2a SC602 strain, as well as to the uropathogenic E. coli CFT073, the non
      pathogenic E. coli Top10, and the probiotic E. coli Nissle 1917 strain. All
      strains colonized and replicated in tumors efficiently each resulting in more
      than 1 x 10(8) colony-forming units per gram tumor tissue. Colonization of spleen
      and liver were significantly lower when E. coli strains were used in comparison
      to S. typhimurium and the non-pathogenic strains did not colonize those organs at
      all. Further investigation of E. coli Nissle 1917 showed that no drastic
      differences in colonization and amplification were seen when immunocompetent and
      immunocompromised animals were used, and we were able to show that E. coli Nissle
      1917 replicates at the border of live and necrotic tumor tissue. We also
      demonstrated exogenously applied L-arabinose-dependent gene activation in
      colonized tumors in live mice. These findings will prepare the way for bacterium
      mediated controlled protein delivery to solid tumors.

PMID- 17448725
TI  - Mechanisms, prediction and treatment of ventricular tachyarrhythmias occurring
      late after myocardial infarction.
AB  - Studies from the 1980s, refined in the intervening years, have examined the
      milieu for ventricular tachycardia (VT) and ventricular fibrillation (VF)
      occurring late after acute myocardial infarction (AMI). The arrhythmogenic
      substrate appears to be patchy areas of fibrous tissue interdigitating with
      viable bundles of myocardium which have distorted orientation and tortuous
      interconnections. These promote conduction delay in sinus rhythm. Factors found
      to promote induction of VT rather than VF are longer conduction delay in sinus
      rhythm, larger infarct size, a more ragged infarct edge and longer ventricular
      extrastimulus coupling intervals. Predictors of spontaneous VT and VF late after
      AMI include inducible VT at electrophysiological studies (EPS), delayed
      conduction in sinus rhythm detected as late potentials on signal-averaged surface
      electrocardiogram (ECG), and low left ventricular ejection fraction (LVEF).
      Treatments of propensity for VT or VF after AMI include insertion of a
      defibrillator (ICD), which has the best track record, antiarrhythmic medication
      (less reliable), and ablation or excision of arrhythmogenic substrate (for
      refractory VT and VF).

PMID- 17448726
TI  - New perspectives on Mars and Venus: unravelling the role of androgens in gender
      differences in cardiovascular biology and disease.
AB  - There are substantial gender differences in the pattern, severity and clinical
      outcomes of coronary heart disease independent of environmental risk factor
      exposure. As a consequence, there has been considerable interest in the potential
      role of sex hormones in atherogenesis, particularly the potential protective
      effects of oestrogen. However, the failure of the recent clinical randomised
      trials to show a cardioprotective effect for oestrogen coupled with a growing
      interest in androgen replacement therapy in elderly men has refocused interest on
      the role of androgens in cardiovascular biology and disease. Over the last
      decade, compelling evidence has emerged that sex differences in vascular biology
      are not only determined by gender-related differences in sex steroid levels but
      also by gender-specific tissue and cellular characteristics which mediate sex
      specific responses to a variety of stimuli. In the vasculature, androgens often
      act in a gender-specific manner, with differential effects in male and female
      cells. This gender-dependent regulation may have important implications for
      understanding the basis of the gender gap in atherosclerosis and may eventually
      lead to the development of sex-specific treatments for cardiovascular disease.
      This review will summarise the current data for the role of androgens in gender
      differences in coronary heart disease and cardiovascular biology.

PMID- 17448727
TI  - Long-term human coronavirus-myelin cross-reactive T-cell clones derived from
      multiple sclerosis patients.
AB  - Autoimmune reactions associated with MS involve genetic and environmental
      factors. Because murine coronaviruses induce an MS-like disease, the human
      coronaviruses (HCoV) are attractive candidates as environmental factors involved
      in a demyelinating pathology. We previously reported the isolation of HCoV
      229E/myelin basic protein (MBP) cross-reactive T-cell lines (TCL) in MS patients.
      To investigate antigenic cross-reactivity at the molecular level, 155 long-term T
      cell clones (TCC) were derived from 32 MS patients by in vitro selection with
      MBP, proteolipid protein (PLP) or HCoV (strains 229E and OC43). Overall, 114 TCC
      were virus-specific, 31 were specific for myelin Ag and 10 other were HCoV/myelin
      cross-reactive. Twenty-eight virus-specific TCC and 7 myelin-specific TCC were
      obtained from six healthy donors. RACE RT-PCR amplification of the Vbeta chains
      of five of ten the cross-reactive TCC confirmed clonality and sequencing
      identified the CDR3 region associated with cross-reactivity. Our findings have
      promising implications in the investigation of the role of molecular mimicry
      between coronaviruses and myelin in MS as a mechanism related to disease
      initiation or relapses.

PMID- 17448728
TI  - The role of perinatal pathological examination in subclinical infection in
      obstetrics.
AB  - Infectious agents are associated with a wide range of obstetric complications and
      pathological processes affecting the placenta, membranes and fetus. In some cases
      there will be associated maternal symptoms and signs indicating an infectious
      aetiology, but in the majority such infection is subclinical, and specific
      diagnosis or confirmation is achieved following pathological examination of the
      delivered placenta and/or fetus. There are two major groups of microorganism
      related mechanisms associated with significant perinatal morbidity and mortality.
      First, ascending genital-tract infection, almost always bacterial, which ranges
      from localized choriodecidual inflammation to frank chorioamnionitis with fetal
      sepsis; this is a major cause of mid-trimester miscarriage and severe preterm
      delivery, and more recent data suggest that it may also have potentially
      important effects via cytokine release mediating neonatal cerebral injury.
      Second, haematogenous spread of maternal systemic infection--bacterial, viral or
      parasitic--which may result in isolated placental effects or transmission to the
      fetus with associated developmental abnormalities and neonatal complications. In
      many cases distinctive histopathological findings are described, and in addition
      a wide range of techniques is now available for culture and microscopy to confirm
      these diagnoses; such techniques include highly specific immunohistochemical
      markers and sensitive molecular diagnostic techniques such as the polymerase
      chain reaction. It is likely that with increasingly widespread availability of
      these investigative approaches to obstetric pathology, a greater understanding of
      the role of infectious agents in obstetric complications will become apparent.

PMID- 17448729
TI  - Embedding quality improvement and patient safety at Liverpool Women's NHS
      Foundation Trust.
AB  - The provision of safe high-quality care in obstetrics and gynaecology is a key
      target in the UK National Health Service (NHS), in part because of the high cost
      of litigation in this area. Good risk management processes should improve safety
      and reduce the cost of litigation to the NHS. This chapter looks at structures
      and processes for improving quality and patient safety, using the stepwise
      approach described by the National Patient Safety Authority (NPSA). This
      encompasses building a safety culture, leading and supporting staff, integrating
      risk management activity, promoting reporting, involving and communicating with
      patients and the public, learning and sharing safety lessons, and implementing
      solutions to prevent harm. Examples from the Liverpool Women's NHS Foundation
      Trust are used to illustrate these steps, including how they were developed, what
      obstacles had to be overcome, ongoing challenges, and whether good risk
      management has translated into better, safer health care.

PMID- 17448730
TI  - Infection and the role of inflammation in preterm premature rupture of the
      membranes.
AB  - Spontaneous preterm birth, caused by preterm labor (contractions before 37 weeks'
      gestation) or preterm premature rupture of the membranes (pPROM) (membrane
      rupture before the onset of labor) or both account for approximately 80% of
      preterm deliveries. pPROM is associated with 30-40% of preterm deliveries and the
      incidence of pPROM has increased in the past decade. The question we address here
      is why some women experience pPROM and some experience preterm labor with no
      rupture of membranes (ROM) when the etiologic factors associated with both these
      pathologic complications are the same. To date, studies had evaluated the markers
      that are commonly elevated in both preterm labor and pPROM. A better
      understanding of the similarities and differences between the biomolecular
      pathways leading to each of these conditions may open new avenues for research
      and intervention. In this chapter we review the role of inflammatory mediators
      (cytokines and matrix metalloproteinases), and programmed cell death (apoptosis)
      in preterm labor with no ROM and preterm labor with pPROM to delineate the
      differences in pathways between the two conditions.

PMID- 17448731
TI  - Tissue Doppler imaging describes diastolic function in men prone to develop
      hypertension over twenty years.
AB  - AIMS: Hypertension is one of several risk factors of cardiovascular disease and
      is associated with left ventricular (LV) systolic and diastolic dysfunction. A
      method for reliably detecting the onset of LV dysfunction before transition to
      irreversible damage of the myocardium would be of crucial importance in subjects
      with essential hypertension. METHODS AND RESULTS: Subjects with clear differences
      in BP level, development and duration of the hypertensive disease were examined
      at the age of 60 yrs: normotensives (n = 17), new hypertensives who developed
      hypertension over a 20 year period (n = 15) and hypertensives (n = 19).
      Relationships between conventional echocardiographic and tissue velocities
      imaging (TVI) parameters compared to LV parameters, and TVI as an estimate of LV
      function were explored. E'(Lat) (TVI peak early diastolic velocity) (P = 0.006)
      and E/E'(Lat) (P = 0.002) demonstrated differences in diastolic function between
      the groups. There were no significant differences regarding systolic myocardial
      velocities. E'(Lat) correlated to S'(Lat) (TDI peak systolic velocity) (r = 0.32,
      P = 0.026) and was independently predicted by S'(Lat) (R(2) = 0.24, P = 0.025) in
      multivariate analysis. E'(Lat) correlated negatively to LV mass index (r = -0.34,
      P = 0.012), also in multivariate regression analysis (R(2) = 0.12, P = 0.032).
      CONCLUSIONS: Myocardial diastolic velocities and mitral flow to annulus velocity
      ratio differentiated LV function between the hypertensive and normotensive
      groups. The parameters probably reflect changes in relaxation, recoil and
      contraction and parallel changes in LV mass index.

PMID- 17448732
TI  - Understanding the minimum clinically important difference: a review of concepts
      and methods.
AB  - BACKGROUND CONTEXT: The effectiveness of spinal surgery as a treatment option is
      currently evaluated through the assessment of patient-reported outcomes (PROs).
      The minimum clinically important difference (MCID) represents the smallest
      improvement considered worthwhile by a patient. The concept of an MCID is offered
      as the new standard for determining effectiveness of a given treatment and
      describing patient satisfaction in reference to that treatment. PURPOSE: Our goal
      is to review the various definitions of MCID and the methods available to
      determine MCID. STUDY DESIGN: The primary means of determining the MCID for a
      specific treatment are divided into anchor-based and distribution-based methods.
      Each method is further subdivided and examined in detail. METHODS: The overall
      limitations of the MCID concept are first identified. The basic assumptions,
      statistical biases, and shortcomings of each method are examined in detail.
      RESULTS: Each method of determining the MCID has specific shortcomings. Three
      general limitations in the accurate determination of an MCID have been
      identified: the multiplicity of MCID determinations, the loss of the patient's
      perspective, and the relationship between pretreatment baseline and posttreatment
      change scores. CONCLUSIONS: An ideal means of determining the MCID for a given
      intervention is yet to be determined. It is possible to develop a useful method
      provided that the assumptions and methodology are initially declared. Our efforts
      toward the establishment of a MCID will rely on the establishment of specific
      external criteria based on the symptoms of the patient and treatment intervention
      being evaluated.

PMID- 17448734
TI  - Impact of lung transplantation on site of death in cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) remains a lethal condition where a palliative
      approach is often taken at the end of life. We wanted to evaluate how lung
      transplantation impacts end of life care in adult CF patients. METHODS: Data were
      abstracted using a standardized data collection instrument from all outpatient
      and inpatient records of adult CF patients with an FEV1< or =30% or prior lung
      transplantation followed at our Center. Comparisons were made between those who
      were listed/received lung transplant and those who were not listed. RESULTS: A
      total of 41 patients met the entry criteria. Of these, 63% (n=26) were referred
      for lung transplant evaluation and 39% (n=16) had undergone lung transplantation.
      Of these 41, 59% (n=24) are deceased. The majority of deceased patients expired
      in an acute care hospital (63%, n=15). There was no difference in site of death
      between the two groups (hospital versus home). However, listed/transplanted
      patients were more likely to die in an intensive care unit setting compared to
      patients not listed/transplanted (p=.013). CONCLUSIONS: Most of our CF patients'
      deaths occurred in an acute care hospital. Lung transplant significantly alters
      site of death and shifts it from medical floors to the intensive care unit.

PMID- 17448733
TI  - Neglected Hangman's fracture in association with rupture of the trachea.
AB  - BACKGROUND CONTEXT: Rupture of the trachea combined with a Hangman's fracture has
      been reported rarely in the literature. We present a case of a rupture of the
      trachea combined with a type IV Hangman's fracture that remained undiagnosed for
      7 weeks, in a 25-year-old woman after a road traffic accident. PURPOSE: To
      underline the necessity that physicians treating patients with multiple injuries
      including the trachea and the mediastinum should be aware of the fact that
      injuries of the trachea can be accompanied by trauma to other contents of the
      mediastinum and of the cervical spine. STUDY DESIGN: A 24-year-old woman was
      involved in a head on collision road traffic accident. She has suffered from a
      rupture of the trachea combined with a type IV Hangman's fracture that remained
      undiagnosed for 7 weeks. METHODS: Emergency surgical repair of the rupture of the
      trachea was performed. A halo vest for a total period of 4 months was applied.
      RESULTS: The patient followed a rehabilitation program, and, at her last visit,
      12 months after her injury, had remained asymptomatic. A computed tomography scan
      of her cervical spine showed union through callous formation, and she had
      returned to her previous job and recreational activities. CONCLUSIONS: Physicians
      treating patients with multiple injuries including the trachea and the
      mediastinum should be aware of the fact that injuries of the trachea can be
      accompanied by trauma to other contents of the mediastinum and of the cervical
      spine.

PMID- 17448735
TI  - Aqueous two-phase recovery of bio-nanoparticles: a miniaturization study for the
      recovery of bacteriophage T4.
AB  - Biotechnology industry has recently been demanding nanoparticulate products (20
      200 nm) such as viruses, plasmids, virus-like particles and drug delivery
      assemblies. These products are mainly used as gene delivery systems in gene
      therapy protocols. During the process development for the manufacture of these
      products, it is crucial to optimize the recovery and purification steps.
      Unfortunately, the high value of some bio-nanoparticles complicates the
      optimization studies. The solvent extraction method with aqueous two-phase
      systems (ATPS) has been used to successfully recover bioproducts on a large
      scale. In this study, the potential miniaturization of ATPS is presented. The
      partition behavior of pure bovine serum albumin (BSA) in PEG-800-phosphate and
      bacteriophage T4 in PEG 8000-phosphate and PEG 600-sulphate systems were studied
      at three different scales (10 g, 2 g and 300 microl). The results obtained showed
      that the volume ratio (V(R)) for BSA (V(R)=1.0) was comparable to the blank
      systems at the scales studied. Additionally, the partition coefficient (K) was
      also similar (K=0.05) with more than 82% of BSA concentrated in the bottom phase.
      Same system was challenged with bacteriophage T4 showing a V(R)=1.0 and K greater
      than 5 with the infective particles concentrated in the top phase. The
      bacteriophage T4 was concentrated in opposite phase in the PEG-600-sulfate system
      with a consistent V(R)=0.8 and K<0.2 for the scales analyzed. The partition
      behavior the bacteriophage T4 was comparable to that reported previously for
      adenoviral vectors in same system at 15 ml scale. The results obtained
      demonstrated that the miniaturization of ATPS is feasible and reproducible for
      the two models selected. This provides significant information about the
      miniaturization process of such ATPS for their potential generic applications in
      the recovery of different bio-nanoparticle products.

PMID- 17448736
TI  - Comment on "determination of treosulfan in plasma and urine by HPLC with
      refractometric detection; pharmacokinetic studies in children undergoing
      myeloablative treatment prior to haematopoietic stem cell transplantation" by
      F.K. Glowka et al. [J. Chromatogr. B 850 (2007) 569-574].

PMID- 17448737
TI  - A mixed-mode liquid chromatography-tandem mass spectrometric method for the
      determination of cytarabine in mouse plasma.
AB  - A novel mixed-mode high performance liquid chromatographic system (HPLC)
      interfaced with an atmospheric pressure chemical ionization (APCI) source and a
      tandem mass spectrometer (MS/MS) was developed for the determination of
      cytarabine (ara-C) in mouse plasma to support pharmacodynamic studies. The mixed
      mode reversed-phase ion-exchange chromatography column was adapted for sufficient
      retention and separation of a small and polar analyte. The impact of the mobile
      phase composition on both chromatographic separation and the ionization
      efficiency of the test compound in the positive mode was investigated. The
      potential of ionization suppression from endogenous biological matrices on the
      mixed-mode LC-APCI/MS/MS method was evaluated using the post-column infusion
      technique. Furthermore, the feasibility of using the mixed-mode HPLC-MS/MS method
      for the determination of the plasma concentrations of cytarabine in mice was
      demonstrated by comparing those obtained by the ion-pairing HPLC-MS/MS method.

PMID- 17448738
TI  - Identification of dauricine and its metabolites in rat urine by liquid
      chromatography-tandem mass spectrometry.
AB  - A rapid, sensitive and specific liquid chromatographic-electrospray ionization
      (ESI) tandem ion trap mass spectrometric method has been developed for
      identification of dauricine and its metabolites in rat urine. Six healthy rats
      were administrated a single dose (100 mg/kg) of dauricine by oral gavage. The
      urine were sampled from 0 to 24 h and purified by using a C18 solid-phase
      extraction (SPE) cartridge, then the purified urine samples were separated on a
      reversed-phase C18 column using methanol/2 mmol/L ammonium acetate (70:30, v/v,
      adjusted to pH 3.5 with formic acid) as mobile phase and detected by an on-line
      MS detector. Identification and structural elucidation of the metabolites were
      performed by comparing their changes in molecular mass (Deltam) and full scan
      MS(n) spectra with those of the parent drug. At least eight metabolites (such as
      N-demethyl, dehydrogenate, demethoxyl, hydroxyl, glucuronide conjugated and
      sulfate conjugated metabolites) and the parent drug were found in rat urine.

PMID- 17448739
TI  - Temperature modulates binding specificity and affinity of the d-trehalose/d
      maltose-binding protein from the hyperthermophilic archaeon Thermococcus
      litoralis.
AB  - We investigated the effect of temperature on the binding specificity of the
      recombinant d-trehalose/d-maltose-binding protein from the hyperthermophilic
      archaeon Thermococcus litoralis (TMBP). Importantly, we found that TMBP can bind
      d-glucose (Glc). The Glc binding was characterized by means of fluorescence
      spectroscopy in the temperature range of 25 degrees C-85 degrees C. Our results
      show that at 25 degrees C the binding of Glc to TMBP is well represented by a
      bimodal model with apparent K(d) of 20 muM and approximately 3-8 mM for the first
      and the second binding step, respectively. At 60 degrees C the binding of Glc to
      TMBP is represented by a simple hyperbolic model with an apparent K(d) value of
      about 40 muM. Finally, at 85 degrees C Glc did not bind to TMBP. Molecular
      dynamics (MD) simulations were used to shed light on the molecular mechanism of
      the Glc binding. Our results suggest that after proper fluorescent labeling TMBP
      can be used as a highly thermostable and non-consuming analyte biosensor for
      monitoring the level of glucose in fluids (e.g. human blood) where other sugars
      are not present.

PMID- 17448740
TI  - Cell spreading correlates with calculated logP of amino acid-modified surfaces.
AB  - The interactions of cells with synthetic surfaces are a critical factor in
      biomaterials design and it would be invaluable if these interactions could be
      precisely controlled and predicted. Hydrophobicity or lipophilicity of the
      surface is commonly used to rationalize cell attachment to materials. In the
      pharmaceutical sciences it is common practice to use logP, the partitioning
      coefficient between water and octanol, as a reliable indicator of the
      hydrophobicity or lipophilicity of (drug) molecules. A number of methods are
      available to reliably predict logP values directly from molecular structure. In
      this paper we demonstrate that logP values calculated on the basis of the
      molecular structure of a range of surface-tethered groups correlate well with
      cell spreading. To our knowledge this is the first method to predict cell
      spreading on chemically modified surfaces via nonspecific interactions.

PMID- 17448742
TI  - Crucial incision method for Stahl's ear reconstruction.

PMID- 17448743
TI  - Functional gracilis flap in thenar reconstruction.
AB  - Restoration of lost opposition in the context of significant thenar soft tissue
      defects represents a tremendous reconstructive challenge. Free functioning muscle
      transfer has been described in this context and has the advantage of providing
      both a functioning muscle unit as well as soft tissue coverage in a single
      reconstructive procedure. It adds to the injured limb, and by sparing donor
      tendons avoids the need for re-education of motor function. We describe the use
      of a free innervated gracilis muscle flap for functional thenar reconstruction in
      two unique cases following extensive traumatic loss of thenar skin and
      musculature. Crucially, in each case, the recurrent motor branch of the median
      nerve had been destroyed at its point of insertion into the thenar muscle
      remnants. AIM: To date, the main reported disadvantages of free functioning
      muscle transfer in thenar reconstruction include difficult flap dissections,
      donor site morbidity, inadequate strength and excursion of the transplanted
      muscle and excessively bulky flaps. Our aim was, as far as possible, to address
      these issues. SURGICAL PROCEDURE: Each thenar defect was measured and a
      corresponding segment of gracilis muscle, measured in situ, was raised on the
      proximal neurovascular pedicle. End-side microvascular anastomosis was performed
      between the medial circumflex femoral artery and the radial artery. The venae
      comitantes of the pedicle were anastomosed end-end with those of the radial
      artery and also with the cephalic vein. Epineural anastomosis was performed
      between the motor branch of the obturator nerve and the recurrent motor branch of
      the median nerve. Each flap was covered with a split thickness skin graft.
      RESULTS: Both flaps survived without any complication. Both patients regained
      excellent voluntary thumb opposition, sufficient to allow return to full-time
      employment, and had restoration of sufficient thenar bulk. This was achieved with
      minimal donor site morbidity. CONCLUSIONS: Restoration of lost opposition, in the
      context of significant thenar soft tissue defects, can be achieved using a free
      functional gracilis flap. This produces clinically excellent functional results
      and can be carried out as a single stage reconstructive procedure. This is a
      novel application of a tremendously versatile donor muscle in functioning free
      muscle transfer.

PMID- 17448744
TI  - Caveolin-1 in extracellular matrix vesicles secreted from osteoblasts.
AB  - Caveolin-1 is an essential and signature protein of caveolae, which are small
      invaginations of the plasma membrane enriched in cholesterol and sphingolipids.
      Although high levels of expression of caveolin-1 have been demonstrated in
      osteoblasts as well as endothelial cells, fibroblasts, and muscular cells, the
      role of caveolin-1 in osteoblasts has not been clarified. Here, we show that
      caveolin-1 is secreted from osteoblasts in the form of matrix vesicles;
      extracellular vesicles released from the plasma membrane of osteoblasts. In this
      study, caveolae and matrix vesicles were similarly enriched in cholesterol and
      sphingomyelin in fractions isolated from mineralizing MC3T3-E1 cells.
      Interestingly, in the MC3T3-E1 cells caveolin-1 was enriched in the matrix
      vesicle fraction as well as the caveolar membrane fraction, and the amount of
      caveolin-1 in the matrix vesicle fraction increased as differentiation
      progressed. Localization of caveolin-1 in matrix vesicles was also confirmed in
      murine tibia. Furthermore, overexpression of caveolin-1 enhanced matrix
      calcification in MC3T3-E1 cells, whereas knockdown of caveolin-1 diminished it.
      These results suggest that secreted caveolin-1 as a component of matrix vesicles
      may play an important role in osteoblast calcification.

PMID- 17448746
TI  - Three recurrent episodes of malrotation in an infant.
AB  - Malrotation with midgut volvulus in a newborn is not a rare condition and Ladd's
      procedure is the recommended surgical treatment. Recurrent volvulus after Ladd's
      procedure is very rare. We present a case of an infant operated on after birth
      for malrotation and midgut volvulus with 2 recurrent similar episodes in the
      following 20 months. We recommend abrasion of the parietal and visceral
      peritoneal surfaces when recurrence of malrotation occurs.

PMID- 17448747
TI  - Carotid body paraganglioma: rare tumor in a 15-year-old adolescent boy.
AB  - We report a 15-year-old adolescent boy with right-side carotid body paraganglioma
      (CBP). The diagnosis of CBP was suspected accidentally because of an asymptomatic
      mass in the right side of the neck and was confirmed by ultrasound, magnetic
      resonance imaging, and carotid arteriography. The CBP was successfully removed
      surgically by complete subadventitial excision without complications or
      neurologic sequelae. In addition, the patient had type 1 diabetes. Recently, it
      has been demonstrated that carotid body plays a role in the glucoregulation in
      vivo and that hypoglycaemic episodes in patients with diabetes may be related to
      alterations of carotid body sensory function. Paragangliomas are extremely rare
      in pediatric age, and it is not clear in our patient if diabetes also has a role
      in the development of CBP. We describe the case and analyse the treatment options
      of CBP.

PMID- 17448748
TI  - Bilateral intralobar pulmonary sequestration in a newborn, case report and review
      of the literature on bilateral pulmonary sequestrations.
AB  - We describe a rare case of bilateral intralobar pulmonary sequestration in a
      newborn with both sequestrations vascularized from a vessel arising from the
      celiac trunk of the abdominal aorta. The larger sequestration on the right side
      was diagnosed antenatally, the left side postnatally. At the age of 7 months, the
      child underwent successful bilateral thoracotomy. In follow-up at the age of more
      than 1 year, no complications have occurred.

PMID- 17448749
TI  - Congenital lingual cysts.
AB  - Congenital lingual cysts are rare congenital tumors of the oropharynx, which
      should be suspected when the tongue appears enlarged by a mass. Prenatal
      diagnosis by ultrasound allows for an optimal management at the time of delivery
      because the mass can obstruct the airways. Unless the cyst enlarges and hinders
      feeding or breathing, surgical treatment is indicated only a few months after
      birth because spontaneous regression can sometimes be observed.

PMID- 17448750
TI  - Paratesticular rhabdomyoma in a young adult: case study and review of the
      literature.
AB  - Paratesticular rhabdomyoma is a rare benign tumor, which usually presents as a
      painless mass in the scrotum or groin. We report the first case of a locally
      invasive paratesticular rhabdomyoma in a 17-year-old male teenager who presented
      with chronic scrotal pain. We further review the current literature of this rare
      tumor.

PMID- 17448751
TI  - A case report of a patient with near total intestinal aganglionosis followed by
      the role of extended myectomy and synbiotics therapy.
AB  - We report our experience with a patient with near-total intestinal aganglionosis
      who underwent extended myectomy-myotomy of the proximal jejunum. At 45 days of
      age, the patient underwent rejejunostomy at 34 cm from the ligament of Treiz
      (LOT) because of enteritis and the bowel rehabilitation therapy was started.
      Because the patient established the swelling and eating enough at 8 months of
      age, an extended myectomy-myotomy was performed when she was 245 days old. A 12
      cm myectomy from the jejunostomy located at 27 cm from the LOT was coupled with a
      30-cm antemesenteric border myotomy. This ultimately left the patient with 65 to
      70 cm of small bowel from the LOT. Synbiotics therapy was performed to prevent
      bacterial translocation, and then central line infection or enteritis was not
      observed at all. The patient was doing well, weighing 9.65 kg, at 2 years of age.
      In conclusion, extended myectomy-myotomy has extended the patient's survival
      period, but it is important and necessary to prevent bacterial translocation and
      to improve intestinal adaptation by synbiotics therapy.

PMID- 17448752
TI  - Consensus statement on mandatory registration of clinical trials.

PMID- 17448753
TI  - Review of radiation risks from computed tomography: essentials for the pediatric
      surgeon.
AB  - BACKGROUND/PURPOSE: Over the past several years, increasing attention has been
      focused on the potential for radiation exposure from computed tomography (CT) for
      inducing the development of cancers. An understanding of these issues is
      important for the practice of pediatric surgery. METHODS: Medline based clinical
      review of current medical literature of the risks for the induction of cancers by
      CT. Data includes estimates of cancer risk from computer models, epidemiologic
      data from survivors of atomic bomb radiation exposure, and consensus opinions
      from expert panels. RESULTS: Review of scientific evidence demonstrates varied
      opinions, but consensus suggests there may be a potential for an increased risk
      of cancer from low level radiation exposure such as from CT. These calculations
      suggest that there may be as high as 1 fatal cancer for every 1000 CT scans
      performed in a young child. CONCLUSIONS: Pediatric surgeons should be aware of
      the potential risks of CT. Minimizing the radiation risks of CT is a complex
      endeavor, and will require investments from pediatric surgeons as well as
      pediatric radiologists.

PMID- 17448754
TI  - Hypoxia upregulates amino acid transport in a human neuroblastoma cell line.
AB  - BACKGROUND/PURPOSE: Some tumor cells survive and even grow in hypoxic conditions.
      We examined the effect of hypoxia on amino acid transport in a human
      neuroblastoma cell line SK-N-SH. METHODS: Cells were incubated under hypoxic
      conditions (1% O2-5% CO2-94% N2). After 0, 8, 16, and 24 hours, the transport of
      3H-glutamine, 3H-glutamate, and 3H-leucine was assayed. 3H-Thymidine and 3H
      leucine incorporation was measured for the determination of DNA and protein
      synthesis, respectively. RESULTS: Hypoxia increased Na+-dependent glutamine and
      Na+-independent leucine transport significantly at 16 and 24 hours compared with
      control (P < .01) by a mechanism that increased Vmax without affecting Km. These
      increases were completely blocked by actinomycin D and cycloheximide. There was
      no significant difference in Na+-dependent glutamate transport between control
      and hypoxic groups. DNA and protein synthesis significantly decreased in the
      hypoxic condition compared with control (P < .01). CONCLUSIONS: This study
      demonstrated that hypoxia upregulates amino acid transport in a human
      neuroblastoma cell line. This mechanism may allow cells to survive and even grow
      under hypoxic conditions.

PMID- 17448755
TI  - Expression of interleukin 6 and apoptosis-related genes in suckling and weaning
      rat models of hepatectomy and liver regeneration.
AB  - BACKGROUND/PURPOSE: The most commonly used model to study the mechanisms of liver
      regeneration is the adult rat submitted to 70% to 80% hepatectomy. However, there
      are no studies using newborn or weaning rat models. The process of liver
      regeneration includes both the hypertrophy and hyperplasia of cells (processes
      regulated by growth factors and cytokines, mainly interleukin 6 [IL-6]) as well
      as apoptosis, or programmed cell death (a process regulated mainly by the Bcl-2
      family of proteins). Proapoptotic proteins in this family include Bax and Bak.
      Conversely, Bcl-2 and Bcl-XL are antiapoptotic regulators. Therefore, to expand
      our understanding of liver regeneration, our study had 2 goals: first, to
      standardize 2 animal models of hepatectomy and liver regeneration using the
      newborn suckling and the weaning rat and second, to quantitate the expression
      levels of IL-6 and several members of the Bcl-2 gene family during the
      regeneration process. METHODS: To create the experimental models, newborn
      suckling rats (age, 5-7 days; weight, 6-10 g) and weaning rats (age, 21-23 days;
      weight, 30-50 g) underwent 70% hepatectomy. The animals were subsequently
      sacrificed at days 1, 2, 3, 4, and 7 after hepatectomy, and the remnant liver
      lobes were harvested for routine histologic examination. Groups of healthy
      animals not operated on served as controls. For the experimental study, 6 newborn
      rats and 6 weaning rats underwent hepatectomy. The animals were killed 1 day
      after liver resection and the remnant livers were harvested to assess gene
      expression by quantitative reverse transcription-polymerase chain reaction. The
      hepatectomized groups were compared with control and sham groups. RESULTS: During
      the creation of the experimental models, 70% of the suckling animals and all the
      weaning animals survived the hepatectomy. The decreased liver weight was
      completely restored to control levels by day 7 after hepatectomy. Histologically,
      the remnant livers of both hepatectomy groups exhibited steatosis, tumefaction of
      hepatocytes, and mitosis, which ceased at 7 days after the hepatectomy. The
      weaning rat model showed more robust gene expression responses. Specifically,
      expression levels of IL-6 gene were significantly increased after both surgical
      insult (sham group) and hepatectomy. However, this increase was significantly
      higher in the latter group. Furthermore, hepatectomy promoted a decrease in the
      expression levels of the proapoptotic genes and an increase in the expression
      levels of Bcl-2. CONCLUSIONS: Our data indicate that regulation of both IL-6 and
      genes involved in apoptosis are strongly implicated in the mechanisms of liver
      regeneration and that the weaning rat model represents an attractive model system
      for future investigations in this area.

PMID- 17448756
TI  - Induction and modulation of apoptosis in neonatal monocytes by polyunsaturated
      fatty acids.
AB  - Polyunsaturated fatty acids (PUFAs), known modulators of the immune response, are
      the source of essential fatty acids in total parenteral nutrition-dependent
      patients. Critically ill infants on TPN have an increased incidence of sepsis,
      and lipid emulsions depress various immune functions. Recent studies have
      demonstrated that PUFAs induce apoptosis in various tissue cells in vitro and ex
      vivo. The susceptibility of neonatal monocytes, as major early effector cells in
      the host response to sepsis, to PUFA-mediated apoptosis and the mechanisms
      associated with PUFA-induced apoptosis were investigated. Both n-3 and n-6 PUFAs
      induced rapid, dose-dependent cell death in purified monocytes. Polyunsaturated
      fatty acids induced significant activation of upstream caspases 8 and 9 as well
      as caspase 3. The PUFA treatment resulted in a 4-fold increase in oxidative
      stress and a loss of monocyte mitochondrial potential compared with carrier
      controls (P < .05). The addition of cyclosporin, which blocks the development of
      mitochondrial transition pores, completely abolished the proapoptotic effects of
      PUFAs. Although Trolox (Sigma Aldrich) reduced PUFA-induced intracellular
      oxidative stress in neonatal monocytes, apoptosis was not blocked by this potent
      antioxidant. The data identify PUFAs as potent inducers of monocyte apoptosis,
      which can occur independently of the induction of oxidative stress, by using a
      mitochondrial dependent pathway. The TPN-dependent infant may be particularly
      sensitive to such PUFA effects, having a relatively poor capacity to both use and
      clear PUFAs.

PMID- 17448757
TI  - Traumatic pancreatic duct injury in children: minimally invasive approach to
      management.
AB  - BACKGROUND: The management of children with main pancreatic duct injuries is
      controversial. We report a series of patients with pancreatic trauma who were
      treated using minimally invasive techniques. METHODS: Retrospective review of
      children with pancreatic trauma treated at a UK tertiary referral institution
      between 1999 and 2004. RESULTS: Fifteen children (11 boys) were admitted with
      pancreatic trauma. Twelve (80%) were less than 50th centile for body weight.
      Contrast-enhanced computed tomography (CT) scans were used to define organ
      injury, supplemented by magnetic resonance cholangiopancreatography (MRCP) in 7.
      Twelve (80%) underwent diagnostic endoscopic retrograde cholangiopancreatography
      (ERCP) with a median time after injury of 11 (range, 6-29) days. The degree of
      pancreatic injury was defined by ERCP and CT/MRCP as grade II (n = 2), grade III
      (n = 4), grade IV (n = 9) (American Association for the Surgery of Trauma
      grades). Nine children had a transductal pancreatic stent inserted
      endoscopically. Computed tomography/ultrasound-guided drainage was performed in 4
      children for acute fluid collections. Two children later underwent endoscopic
      cyst-gastrostomy, one of whom later required conversion to an open cyst
      gastrostomy. CONCLUSION: Body habitus may predispose to pancreatic duct trauma.
      Contrast-enhanced CT scan (and MRCP) should dictate the need for ERCP.
      Transductal pancreatic stenting allows internal drainage of peripancreatic
      collections and may reestablish duct continuity, although a proportion still
      requires percutaneous or endoscopic cyst-gastrostomy drainage. Open surgery for
      pancreatic trauma should now be an exception.

PMID- 17448758
TI  - Increasing tendency in caustic esophageal burns and long-term
      polytetrafluorethylene stenting in severe cases: 10 years experience.
AB  - In recent years, lye products have come into common household use in Turkey.
      Unfortunately, we have noted more cases of serious corrosive esophagitis owing to
      accidental caustic agent ingestion. The aims of this study were to (1) evaluate
      our experience with these cases and (2) investigate the effects of long-term
      intraesophageal polytetrafluorethylene stenting on esophageal remodeling and its
      impact upon the need for esophageal replacement. Between 1997 and 2006, 68
      patients (44 males and 22 females) with accidental caustic agent ingestion were
      admitted to our department, the only tertiary care referral center for the
      Turkish Army. Once stabilized, esophagoscopy was performed for injury grading
      (grades 0, 1, 2a, 3b, 3a, or 3b) as described by Millar and Cywes (Pediatric
      Surgery. 1998;969-979). Esophagogram was performed 3 weeks after injury to assess
      healing. At presentation, the injury grade for 24, 31, 11, and 1 cases were 0 or
      1, 2a, 2b, and 3a, respectively. One case had gastric outlet obstruction. All
      cases of grade 0 or 1 injuries had a normal esophagogram at 3 weeks postinjury.
      For the remaining 44 patients, several treatment modalities have been applied,
      including antegrade and retrograde dilatations in 31 grade 2a patients,
      intraluminal stenting in 11 grade 2b patients, esophageal reconstruction in 1
      grade 3a patient, and gastroenterostomy in 1. Of the 11 patients with esophageal
      stenting, 8 patients have resumed a normal diet after 9 to 14 months of stenting.
      Mean follow up duration is 3.5 years (1-6 years) after stent removal. In the
      remaining 3 cases, treatment is still ongoing. Esophagitis and esophageal
      structuring because of caustic agent ingestion is a major public health problem
      in Turkey. Our small uncontrolled pilot series suggests that intraluminal
      polytetrafluorethylene stenting may be an effective treatment method to reduce
      the need for major surgical reconstruction of recalcitrant esophageal strictures.

PMID- 17448759
TI  - Esophageal smooth muscle reactivity is impaired in chronic reflux esophagitis by
      both receptor- and nonreceptor-mediated mechanisms.
AB  - AIM: Esophagitis is associated with an impaired esophageal peristalsis. A few
      studies have been aimed at understanding the pathophysiology of abnormal
      peristaltic activity. The mechanism of impaired esophageal smooth muscle
      reactivity in the chronic gastroesophageal reflux (GER) model is investigated in
      vitro for the first time. MATERIALS AND METHODS: The chronic GER rat model was
      created by partial gastric outlet obstruction. The histopathological findings
      related to esophagitis were evaluated. Smooth muscle strips of the tunica
      muscularis mucosa of esophagus were studied in standard organ chambers. Carbachol
      and KCl-induced contractile responses and serotonin- and papaverine- induced
      relaxant responses in both reflux and sham-operated control groups were
      determined. RESULTS: Histopathologically, chronic reflux esophagitis was observed
      in all specimens of the reflux group. Contractile (carbachol- and KCl-induced)
      smooth muscle responses were significantly decreased in the reflux group. When
      compared to control group, relaxant response of smooth muscle to serotonin was
      also significantly decreased in the reflux group. However, there was no
      difference in papaverine-induced relaxant responses between 2 groups.
      CONCLUSIONS: Our study describes the effects of chronic GER on rat esophageal
      smooth muscle contractility in vitro. We found that both receptor- (carbachol,
      serotonin) and nonreceptor-mediated (KCl) esophageal smooth muscle reactivity
      were impaired in chronic reflux esophagitis. These changes may correspond to the
      functional motor abnormalities of the esophagus seen in patients with chronic
      reflux esophagitis.

PMID- 17448760
TI  - Effect of chronic renal failure on foregut smooth muscle reactivity: an
      experimental study.
AB  - PURPOSE: An association between chronic renal failure (CRF) and gastroesophageal
      reflux (GER) is well known. The aim of this study was to pharmacologically
      characterize and investigate the possible contribution of smooth muscle
      reactivity pathways involving GER on the CRF rat model. MATERIAL AND METHODS:
      Chronic renal failure was created in Sprague-Dawley rats by 5 of 6 nephrectomy.
      The rats were divided into 2 groups: the CRF-induced group (CRF group) and the
      sham-operated group (control group). Esophageal smooth muscle strips were studied
      in vitro for their contractile (KCl, carbachol) and relaxant (isoproterenol,
      serotonin, and papaverine) response to receptor activation in the organ chambers
      set up. Subsequently, the in vitro lower esophageal sphincter (LES) smooth muscle
      study was generated by KCl, carbachol, isoproterenol, nicotine, sodium
      nitroprusside (SNP), and papaverine. RESULTS: Compared with controls, esophageal
      strips taken from CRF-induced rats associated with decreased smooth muscle
      responses to carbachol, serotonin, and increased response to KCl. Isoproterenol-
      and papaverine-induced relaxant responses were not affected. Contractility of the
      isolated LES strips were significantly increased to KCl and carbachol in the CRF
      group compared with the control group. Similar relaxant responses were obtained
      in LES strips stimulated by isoproterenol, SNP, and papaverine in the CRF and
      control group. Nicotine-induced relaxant responses were decreased in the CRF
      group compared with the control group. CONCLUSIONS: Our study revealed
      alterations of receptor-dependent esophageal and LES smooth muscle reactivity in
      the CRF-induced rats. Impaired foregut smooth muscle reactivity may contribute to
      the development of GER-related functional abnormalities in patients with CRF.

PMID- 17448761
TI  - A reinforced suture line prevents recurrence after fundoplication in patients
      with familial dysautonomia.
AB  - BACKGROUND/PURPOSE: Long-term follow-up of fundoplication in patients with
      familial dysautonomia (FD) has revealed a high rate of recurrent gastroesophageal
      reflux. This may be because of the unique characteristics of patients with FD
      which include autonomic denervation accompanied by cyclic vomiting and retching.
      We reviewed our results with adaptations to the Nissen fundoplication to
      determine which would be most effective in preventing the need for reoperation.
      METHODS: We reviewed the records of 108 patient with FD who underwent
      fundoplication by a single pediatric surgeon from November 1978 to July 1, 2004.
      Patients were divided into 4 groups based on the operative technique: standard
      Nissen fundoplication, Nissen with a posterior gastropexy, Nissen with posterior
      gastropexy and a superior anchoring suture, and Nissen with a reinforced suture
      line in addition to the previous modifications. Demographic data and surgical
      outcomes were abstracted. RESULTS: Patients who underwent a Nissen fundoplication
      with a reinforced suture line were significantly less likely to require a
      reoperation for recurrent reflux than any other patients (P = .05, Fisher's Exact
      test) despite the fact that they were younger than patients who underwent a
      standard Nissen alone. CONCLUSION: The addition of a reinforced suture line to
      the standard Nissen fundoplication decreases the failure rate for patients with
      gastroesophageal reflux and FD. A reinforced suture line may be an attractive
      modification for patients where the fundoplication may be under continued
      physical stress caused by autonomic perturbations, or other conditions such as
      uncontrolled seizures or progressive neurologic decline.

PMID- 17448762
TI  - Long-term functional impact of congenital diaphragmatic hernia repair on
      children.
AB  - BACKGROUND/PURPOSE: Congenital diaphragmatic hernia (CDH) is a malformation
      requiring neonatal surgical repair with in-hospital survival rates above 90%. We
      examined the long-term functional impact of CDH repair on a cross-sectional
      cohort of survivors. METHODS: A cohort of 53 CDH families participated in this
      study. Functional impact was evaluated with parent report of the Functional
      Status IIR and the Child Health Ratings Inventories General Health Module.
      Parents also provided a clinical severity score, the child's medical history, and
      family demographic information. The primary outcome was the effect of medical
      morbidity on the Functional Status IIR total score. RESULTS: Congenital
      diaphragmatic hernia survivors had a median age of 8 years; 50% were in third
      grade or above. Sixty-six percent had major medical issues at hospital discharge,
      whereas 48% had current clinical problems. Functional Status IIR total score was
      strongly correlated with child's clinical severity (r = -0.65; P < .0001) and was
      lower among children with ongoing medical morbidity, denoting worse functioning
      (P = .01). Child Health Ratings Inventories General Health Module scores followed
      a similar pattern. CONCLUSIONS: A subset of long-term CDH survivors continues to
      have ongoing clinical problems a median of 8 years after surgery, translating to
      lower functional status. Affected children and their families may benefit from
      prospective identification and ongoing interventions.

PMID- 17448763
TI  - Application of HapMap data to the evaluation of 8 candidate genes for pediatric
      slow transit constipation.
AB  - BACKGROUND: Slow transit constipation (STC) affects up to 3% of all children and
      is an increasingly recognized cause of chronic constipation in children. We
      conducted a pilot study to investigate whether genes encoding neurotransmitters
      (TAC1, TAC3, VIP, NOS1) and receptors (TACR1, TACR2, TACR3, KIT) could be
      responsible for STC. METHODS: One hundred seventeen tag single nucleotide
      polymorphisms (SNPs), distributed among the candidate genes, were selected from
      HapMap data and genotyped using Sequenom (San Diego, CA) technology in 35
      affected families. Evaluation of association was performed by transmission
      disequilibrium test and multilocus analysis. RESULTS: Five SNPs (rs3771863,
      rs4580655, rs11722288, rs4563545, and rs3782221) in the TACR1, TACR3, KIT, and
      NOS1 genes were found to be potentially associated with STC, although the
      significance of these results does not withstand correction for multiple testing.
      CONCLUSIONS: Our data indicate that 5 SNPs in the NOS1, TACR1, TACR3, and KIT
      genes could be involved in STC, especially rs3771863 in intron 1 of TACR1, which
      showed the highest association.

PMID- 17448764
TI  - Botulinum toxin, a new treatment modality for chronic idiopathic constipation in
      children: long-term follow-up of a double-blind randomized trial.
AB  - BACKGROUND: Myectomy of the internal anal sphincter (IAS) has been performed on
      some children after failure of medical treatment to treat idiopathic
      constipation. The aim of this study was to compare botulinum toxin injection with
      myectomy of the IAS in the treatment of chronic idiopathic constipation and
      soiling in children. METHODS: This was a double-blind randomized trial. Patients
      between 4 and 16 years old were included in the study if they had failed to
      respond to laxative treatment and anal dilatation for chronic idiopathic
      constipation. All study patients had anorectal manometry and anal endosonography
      under ketamine anesthesia. Outcome was measured using a validated symptom
      severity (SS) scoring system, with scores ranging from 0 to 65. RESULTS: Of 42
      children, 21 were randomized to the botulinum group and 21 were randomized to the
      myectomy group. At the 3-month follow-up, the median preoperative SS score
      improved from 34 (range = 19-47) to 20 (range = 2-43) in the botulinum group (P <
      .001) and from 31 (range = 18-49) to 19 (range = 3-47) in the myectomy group (P <
      .002). At the 12-month follow-up, the scores were 19 (range = 0-45) and 14.5
      (range = 0-41) for the botulinum group and the myectomy group, respectively (P <
      .0001). There was no complication in both groups. CONCLUSION: Botulinum toxin is
      equally effective as and less invasive than myectomy of the IAS for chronic
      idiopathic constipation and fecal incontinence in children.

PMID- 17448765
TI  - Prenatal ultrasonographic and magnetic resonance imaging findings of congenital
      cloacal anomalies associated with meconium peritonitis.
AB  - BACKGROUND/PURPOSE: Cloacal malformations are rare anomalies, occurring in
      females, and in which they demonstrate a single perineal orifice for urethra,
      vagina, and rectum. Prenatal ultrasonograms (US) of cloacal malformations
      sometimes show ascites, hydrocolpos, and hydronephrosis. We herein describe the
      characteristic prenatal US and magnetic resonance imaging (MRI) findings of the
      cloacal malformations associated with meconium peritonitis. METHODS: The pre- and
      postnatal records of 11 newborn patients with cloacal malformations, treated in
      our hospital from 1988 to 2004, were reviewed. All fetuses underwent prenatal US
      by experienced obstetricians, whereas in addition, fetal MRI was performed in 1
      patient. RESULTS: The prenatal US and/or MRI findings showed fetal ascites, a
      multicystic pelvic mass, oligohydramnios, and bilateral hydronephrosis in 5 of 11
      patients with cloacal malformations. In these 5 cases, postnatal examinations
      showed associated hydrocolpos, hydrometrocolpos, and bilateral hydronephrosis;
      furthermore, 4 of these 5 cases also showed meconium peritonitis at laparotomy.
      CONCLUSIONS: The prenatal US and MRI findings, showing fetal ascites, multicystic
      pelvic mass, bilateral hydronephrosis, and oligohydraminios are highly suggestive
      of the cloacal malformations associated with meconium peritonitis.

PMID- 17448766
TI  - Coming face to face with the stenotic MACE-combined Maceoscopy and colonoscopy
      (the rendez-vous procedure): a preliminary report.
AB  - OBJECTIVE: The aim of our study was to review the management of stomal stenosis
      after the Malone antegrade continence enema (MACE) procedure at our center, and
      to describe and assess the early outcomes of 2 novel procedures used in the
      management of conduit stenosis: Maceoscopy and the rendez-vous. SUBJECTS/PATIENTS
      AND METHODS: We retrospectively reviewed 45 consecutive MACE cases performed by 1
      surgeon at St George's hospital over a 13-year period. RESULTS: Until April 2002,
      5 cases presented with difficulty catheterizing their MACE. This was attributed
      to stenosis without further investigation, and the MACE revised surgically. Of 13
      cases presenting with suspected stenosis since May 2002, 8 channels turned out to
      be patent when assessed and catheterized endoscopically via Maceoscopy. Two truly
      stenotic MACEs were revised; patency of the other 3 was reestablished by means of
      a new double-endoscopic procedure we have termed the rendez-vous.

PMID- 17448767
TI  - Duhamel operation vs neonatal transanal endorectal pull-through procedure for
      Hirschsprung disease: which are the changes for pathologists?
AB  - BACKGROUND: The aim of this study was to evaluate whether performing definitive
      surgery for Hirschsprung disease (HD) in neonatal period with a transanal
      endorectal pull-through (TEPT) procedure had modified our diagnostic relevance,
      particularly during intraoperative frozen sections (IOFS), compared to classic
      Duhamel (DH) surgery performed in older children. METHODS: We collected
      pathologic data for 47 children who underwent surgery for neonatal nontotal HD
      over a 5-year period. RESULTS: Twenty-nine patients underwent TEPT and 18 the DH
      operation. Mean age at operation was 19 days for TEPT and 4 months for DH
      operation. The mean number of IOFS was 2.6 for TEPT and 2.4 for DH operation.
      Gross examination could be fully completed in all TEPT cases, but was incomplete
      in 5 DH cases. The average total lengths of bowel, and aganglionic, transitional,
      and ganglionic segments were 12.3, 7.3, 3, and 2 cm for TEPT, and 17.6, 9.3, 3.5,
      and 4.8 cm for DH operation, respectively. Discordance between IOFS and paraffin
      section analysis occurred in 5 cases (3 TEPT and 2 DH operation). CONCLUSION:
      When TEPT was used, the gross examination and sampling was more accurate, leading
      to a clearer pathology report. The TEPT procedure facilitates the work of the
      pathologist without modifying the results of IOFS, if some precautions are taken.

PMID- 17448768
TI  - Laparoscopic pyloromyotomy for hypertrophic pyloric stenosis: a prospective,
      randomized controlled trial.
AB  - BACKGROUND: Several authors have reported on laparoscopic pyloromyotomy (LP)
      since the technique was originally described in 1990, but its benefits remain
      unproven. We performed a randomized controlled trial comparing LP to open
      circumumbilical pyloromyotomy (OP) for hypertrophic pyloric stenosis. METHODS: In
      a prospective study, 102 infants with pyloric stenosis were randomly assigned to
      either LP (n = 50) or OP (n = 52). The primary outcome measure was the incidence
      of postoperative vomiting; the secondary parameters were the durations of surgery
      and anesthesia, surgical complications, and postoperative pain. All infants were
      managed according to standardized procedures regarding general anesthesia,
      surgical technique, postoperative analgesia, and feeding regimen. Parents,
      carers, and assessors responsible for the postoperative evaluation were blinded
      for the technique used. RESULTS: There was no difference in the incidence of
      postoperative vomiting between the 2 groups. The overall incidence of
      complications was similar, but the durations of surgery and general anesthesia
      were significantly longer in the LP group than in the OP group (P = 10(-4) and P
      = .02, respectively). There were 3 cases of incomplete pyloromyotomy after
      laparoscopy, requiring a repeat procedure. CONCLUSIONS: Laparoscopic
      pyloromyotomy does not decrease the incidence of postoperative vomiting, has a
      similar complication rate compared with the open umbilical approach, but may
      expose patients to a risk of inadequate pyloromyotomy.

PMID- 17448769
TI  - Perinatal testicular torsion: a unique strategy.
AB  - BACKGROUND/PURPOSE: Perinatal testicular torsion (PTT) is defined as testicular
      torsion occurring prenatally or within the first 30 days of life. The aim of this
      study was to evaluate the data obtained from patients with PTT and propose
      principles of management based on clinical, surgical, and histologic findings.
      METHODS: A retrospective analysis of 27 boys seen between 1990 and 2005 with
      surgically documented PTT was conducted. Patients were divided into 2 groups: A,
      prenatal testicular torsion; B, postnatal testicular torsion. The presence of
      acute scrotal inflammatory signs defined the urgency to operate. RESULTS: There
      were 4 clinical pictures in group A: A1, patients with a nubbin testis (n = 3);
      A2, patients with a small and hard testis (n = 12); A3, patients with a normal
      sized and hard testis (n = 8); and A4, patients with an acute scrotum (n = 2).
      Group B (n = 2) presented no sign after birth and later developed an acute
      scrotum. Surgical exploration and histologic examination showed clear signs of a
      long-standing testicular torsion in groups A1, A2, and A3 or a recent-onset
      testicular torsion in groups A4 and B. Only one testis could be salvaged (group
      B). CONCLUSIONS: Clinical signs correlated very well with surgical and histologic
      findings and can define the need and the urgency to operate. Although testicular
      salvage rate is very low, the affected side always should be explored to confirm
      the diagnosis and to fix or remove the affected testicle. The contralateral
      scrotum also should be explored because of the risk of asynchronous contralateral
      testicular torsion.

PMID- 17448770
TI  - The initial experience of antithrombin III in the management of neonates with
      necrotizing enterocolitis.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC), the devastating enteric process of
      premature neonates, is marked by severe intravascular abnormalities and
      disseminated intravascular coagulation. Treatment to date remains historical and
      continues to be merely supportive without attempts to ameliorate progress within
      the inflammatory or coagulation cascades. Antithrombin III (ATIII)
      supplementation has been shown to favorably alter the process of disseminated
      intravascular coagulation and sepsis in adults. However, no reported use of this
      treatment exists in neonates. Therefore, we analyze the efficacy of our recent
      experience with ATIII replacement therapy in neonates with NEC. METHODS: Age and
      diseased-matched controls with NEC were identified before the introduction of
      ATIII in our institution and compared against neonates with NEC undergoing ATIII
      replacement for diminished ATIII levels. Data collected included demographics,
      course of treatment parameters, and outcomes. Course of treatment parameters
      included hemoglobin, platelet count, prothrombin time, and partial thromboplastin
      time over the first 10 consecutive days of treatment. Outcome variables included
      packed red blood cell, platelet, fresh frozen plasma, and cryoprecipitate
      transfusions, as well as transfusion cost, length of stay, and survival. RESULTS:
      Over a 5-year period, 19 neonates with NEC received ATIII and were compared to 17
      historical controls. Treatment hematologic profiles were not worsened in the
      ATIII-treated patients. The control patients received less overall transfusions
      and had a shorter length of stay. CONCLUSION: Antithrombin III appears to be safe
      in neonates with NEC, and its impact on reversing intravascular pathology in
      these patients warrants more thorough investigation.

PMID- 17448771
TI  - Celiac trunk compression syndrome requiring surgery in 3 adolescent patients.
AB  - BACKGROUND/METHODS: Celiac trunk compression syndrome is a rare cause of
      recurrent, nonspecific upper abdominal pain. In this article, we present 3 cases
      of celiac trunk compression syndrome in 15- and 16-year-old adolescents who were
      treated surgically in our clinic and discuss our findings with existing
      literature. RESULTS: All 3 adolescents complained about unspecific upper
      gastrointestinal pain. The performance of digital subtraction angiography and,
      accordingly, magnetic resonance angiography showed, respectively, a stenosis and
      an occlusion of the celiac artery. In all cases, a decompression of the celiac
      trunk as well as a resection of the celiac plexus in the region near the outlet
      of the trunk was performed. Patients have been surveyed between 12 and 18 months
      postoperatively. In all cases, the gastrointestinal symptoms have completely
      disappeared. DISCUSSION: Celiac artery compression syndrome is understood to
      consist of symptoms of recurrent pain, caused by a neurovascular narrowing of the
      aortic hiatus and celiac trunk. The surgical approach of choice is sharp
      transection of the median arcuate ligament, along with complete resection of the
      nerve fibers of the celiac plexus with or without performance of
      revascularisation. In summary, celiac trunk compression syndrome is a rare cause
      of recurrent epigastric pain that should be not be ignored completely as a
      differential diagnosis.

PMID- 17448772
TI  - Bilious vomiting in the newborn: how often is further investigation undertaken?
AB  - BACKGROUND/PURPOSE: Pediatric surgeons consider bile vomiting in the neonate a
      potential surgical emergency. The reported rate of surgical intervention is 30%
      to 40%, but as most neonates are born outwith pediatric surgical centers,
      referral of these babies is at the neonatologists' discretion. The aim of this
      study was to determine the referral policy of neonatologists in the West of
      Scotland for a neonate with bile vomiting. METHODS: Questionnaires were sent to
      all neonatologists in the West of Scotland to determine the management plan for a
      neonate with a single bile vomit or repeated bile vomits. Respondents were asked
      to indicate whether they would advocate postnatal ward observation, admission to
      the special care baby unit, abdominal x-ray, or upper gastrointestinal contrast
      study, or refer to pediatric surgeons. Respondents were asked to prioritize these
      options numerically. RESULTS: A return rate of 81% was achieved. Most
      neonatologists (80%) would admit a neonate with a single bile vomit to the
      special care baby unit, but more than 50% did not consider an upper
      gastrointestinal contrast study appropriate. One third felt that pediatric
      surgical referral is not appropriate for a single bile vomit. In a neonate with
      persistent bile vomiting, pediatric surgical referral was considered the highest
      priority. CONCLUSION: Neonatologists use a policy of observation for neonates
      with a single bile vomit. Those neonates with no further bile vomiting are
      unlikely to be referred. Pediatric surgeons are not referred a significant
      proportion of neonates that vomit bile.

PMID- 17448773
TI  - Gastric hemangioma in a 5-year-old boy.
AB  - We report a rare cause of gastrointestinal bleeding in a 5-year-old boy with
      hematemesis and melena for a month. Upper gastrointestinal endoscopy and an
      abdominal magnetic resonance image suggested a large hemangioma on the gastric
      fundus. The patient underwent an exploratory laparotomy with partial gastrectomy
      limited to the gastric fundus. An intraoperative endoscopy helped to ensure a
      complete resection of the tumor. Histopathology showed a cavernous hemangioma of
      the gastric fundus.

PMID- 17448774
TI  - Injuries to the major airway after blunt thoracic trauma in children: review of 2
      cases.
AB  - Tracheobronchial injuries in children occur rarely. Their diagnosis is often very
      difficult and needs a high degree of suspicion, with in-depth knowledge of the
      anatomy of and radiological findings for the chest. With proper surgical
      management, even a delayed diagnosis can result in normal lung function. We
      discuss 2 cases of major airway injuries with successful outcomes and present
      some interesting surgical maneuvers.

PMID- 17448775
TI  - Urachal remnant perforation during umbilical vein catheterization in a newborn.
AB  - Urachal remnants are uncommon congenital anomalies of the bladder that can be
      injured during attempted catheterization of an umbilical artery or vein. We
      present the case of a newborn boy who developed urinary ascites after undergoing
      an attempted umbilical vein catheterization. He subsequently underwent successful
      surgical repair of a perforated urachal remnant.

PMID- 17448776
TI  - Neuroglial disorders of central and peripheral nervous systems in a patient with
      Hirschsprung's disease carrying allelic SOX10 truncating mutation.
AB  - BACKGROUND/PURPOSE: Recent biologic studies have revealed that enteric neuroglial
      deficiency causes gut functional deterioration. We studied the central and
      peripheral nervous systems in a SOX10 mutation-associated Hirschsprung's patient
      who presented persistent gut functional disorders even after definitive surgery.
      METHODS: DNA sequences of all coding regions of the SOX10 gene (22q13) were
      determined using the direct DyeDeoxy Terminator Cycle method, and brain magnetic
      resonance images, nerve conduction velocities, and histopathology of the enteric
      nervous system were investigated for neurologic assessment. RESULTS: DNA analysis
      revealed a heterozygous nucleotide deletion (778delG) in SOX10 exon 5, causing a
      frameshift at codon 260 and resulting in premature transcriptional termination at
      codon 285. Neurologic studies disclosed brain hypomyelination, peripheral
      dysmyelinating neuropathy, and enteric neuroglia deficiency, which exclusively
      implied systemic glial maldevelopment. CONCLUSION: These results suggest that the
      enteric nervous system in patients with SOX10-associated Hirschsprung's disease
      is entirely subject to neuroglial impairment. This may explain persistent gut
      motility and absorption insufficiency after pull-through surgery, especially in
      children with allelic SOX10 truncating mutations.

PMID- 17448777
TI  - Infantile visceral myofibromatosis--a rare cause of neonatal intestinal
      obstruction.
AB  - Infantile myofibromatosis (IM) is a rare cause of intestinal obstruction in the
      newborn. A neonate with generalized IM having multifocal intestinal lesions
      presenting with intestinal obstruction is reported here. Unique intraoperative
      pictures are provided. The presentation, management, and the prognosis of IM are
      discussed.

PMID- 17448778
TI  - Giant anterior urethral diverticulum in a neonate.
AB  - Congenital anterior urethral diverticulum is an uncommon condition that tends to
      present in older children with signs of chronic urinary problems. A neonate
      presented following recurrent collapse, and cystography revealed a giant urethral
      diverticulum. The diverticulum was incised at cystoscopy, leading to a full
      recovery.

PMID- 17448779
TI  - Osteosarcoma with delayed metastasis to the stomach.
AB  - This case illustrates a primary osteosarcoma in a child that has metastasized to
      the stomach. Such a presentation has only been documented once before and raises
      the importance of vigilant and thorough follow-up. In addition, this case
      questions the relationship of prolonged treatment and subsequent sites of
      recurrence.

PMID- 17448780
TI  - Central pancreatectomy with pancreaticogastrostomy in children.
AB  - Children requiring surgical intervention for pancreatic disease may be at risk
      long term for exocrine insufficiency and glucose intolerance. Pediatric surgeons
      must balance the need to perform adequate surgical resection while preserving as
      much normal pancreatic parenchyma as possible. Neoplasms of the middle pancreatic
      segment with low malignant potential and isolated trauma to the pancreatic body
      or neck represent 2 conditions where extensive pancreatic resection is
      unnecessary. Central pancreatectomy for such lesions is well described in adults.
      Reconstruction of the distal pancreatic remnant is traditionally performed via
      Roux-en-Y pancreaticojejunostomy. Pancreaticogastrostomy is an alternative
      approach that has been used to reconstruct the distal pancreas in the adults.
      Pancreaticogastrostomy offers several technical advantages over
      pancreaticojejunostomy. Because children may be uniquely susceptible to the long
      term consequences of excessive pancreatic resection, 2 cases using this technique
      of central pancreatectomy with pancreaticogastrostomy are described.

PMID- 17448781
TI  - Giant isolated cavernous hemangioma of the stomach.
AB  - Giant isolate cavernous hemangiomas of the stomach are extremely rare. An eight
      year old boy with recurrent episodes of massive hematemesis and involvement of
      both the anterior and posterior walls of the stomach is presented. Awareness of
      the lesion, a combination of endoscopy and contrast enhanced CT scan are helpful
      in reaching a diagnosis. Surgical excision is curative.

PMID- 17448782
TI  - Bombesin protection against FK506 neurotoxicity.

PMID- 17448783
TI  - Endoscopic removal of frontozygomatic benign tumors.

PMID- 17448786
TI  - Unusual two-component signal transduction pathways in the actinobacteria.

PMID- 17448787
TI  - Acyl-HSL signal decay: intrinsic to bacterial cell-cell communications.

PMID- 17448788
TI  - Microbial exoenzyme production in food.

PMID- 17448789
TI  - Biogenetic diversity of cyanobacterial metabolites.

PMID- 17448790
TI  - Pathways to discovering new microbial metabolism for functional genomics and
      biotechnology.

PMID- 17448791
TI  - Biocatalysis by dehalogenating enzymes.

PMID- 17448792
TI  - Lipases from extremophiles and potential for industrial applications.

PMID- 17448793
TI  - In situ bioremediation.

PMID- 17448794
TI  - Bacterial cycling of methyl halides.

PMID- 17448795
TI  - Has the time come for sentinel lymph node biopsy alone in radical hysterectomy
      patients?

PMID- 17448796
TI  - On the road: accidents that should not happen.

PMID- 17448797
TI  - Australia: the politics of fear and neglect.

PMID- 17448798
TI  - Improving access to second-line antiretrovirals.

PMID- 17448799
TI  - Global poliomyelitis eradication: status and implications.

PMID- 17448800
TI  - Surveillance of acute flaccid paralysis in India.

PMID- 17448801
TI  - Limits of substance-use interventions in developing countries.

PMID- 17448802
TI  - Morphine kills the pain, not the patient.

PMID- 17448803
TI  - Give a drug a good name.

PMID- 17448804
TI  - Frailty in elderly people.

PMID- 17448805
TI  - Clinical update: management of stroke.

PMID- 17448806
TI  - Tatsuo Kurokawa: keeping watch on drug safety in Japan.

PMID- 17448807
TI  - Postgraduate Medical Education and Training Board (PMETB).

PMID- 17448808
TI  - MRI versus CT in acute stroke.

PMID- 17448810
TI  - MRI versus CT in acute stroke.

PMID- 17448811
TI  - MRI versus CT in acute stroke.

PMID- 17448812
TI  - Gastrointestinal safety of NSAIDs versus COX-2 inhibitors.

PMID- 17448813
TI  - Meningococcal vaccine coverage in Hajj pilgrims.

PMID- 17448814
TI  - Gastrointestinal safety of NSAIDs versus COX-2 inhibitors.

PMID- 17448816
TI  - Taiwan-China health partnership is urgently needed for all.

PMID- 17448818
TI  - Legal limits for paracetamol sales.

PMID- 17448819
TI  - Sluggish sperms.

PMID- 17448820
TI  - The efficacy and safety of enoxaparin versus unfractionated heparin for the
      prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL
      Study): an open-label randomised comparison.
AB  - BACKGROUND: Venous thromboembolism prophylaxis with low molecular weight heparin
      or unfractionated heparin is recommended in acute ischaemic stroke, but which
      regimen provides optimum treatment is uncertain. We aimed to compare the efficacy
      and safety of enoxaparin with that of unfractionated heparin for patients with
      stroke. METHODS: 1762 patients with acute ischaemic stroke who were unable to
      walk unassisted were randomly assigned within 48 h of symptoms to receive either
      enoxaparin 40 mg subcutaneously once daily or unfractionated heparin 5000 U
      subcutaneously every 12 h for 10 days (range 6-14). Patients were stratified by
      National Institutes of Health Stroke Scale (NIHSS) score (severe stroke > or =14,
      less severe stroke <14). The primary efficacy endpoint was the composite of
      symptomatic or asymptomatic deep vein thrombosis, symptomatic pulmonary embolism,
      or fatal pulmonary embolism. Primary safety endpoints were symptomatic
      intracranial haemorrhage, major extracranial haemorrhage, and all-cause
      mortality. This study is registered with ClinicalTrials.gov, number NCT00077805.
      FINDINGS: In the efficacy population (ie, one or more dose received, presence of
      deep vein thrombosis or pulmonary embolism, or assessment for venous
      thromboembolism), enoxaparin (n=666) and unfractionated heparin (669) were given
      for 10.5 days (SD 3.2). Enoxaparin reduced the risk of venous thromboembolism by
      43% compared with unfractionated heparin (68 [10%] vs 121 [18%]; relative risk
      0.57, 95% CI 0.44-0.76, p=0.0001; difference -7.9%, -11.6 to -4.2); this
      reduction was consistent for patients with an NIHSS score of 14 or more (26 [16%]
      vs 52 [30%]; p=0.0036) or less than 14 (42 [8%] vs 69 [14%]; p=0.0044). The
      occurrence of any bleeding was similar with enoxaparin (69 [8%]) or
      unfractionated heparin (71 [8%]; p=0.83). The frequency of the composite of
      symptomatic intracranial and major extracranial haemorrhage was small and closely
      similar between groups (enoxaparin 11 [1%] vs unfractionated heparin 6 [1%];
      p=0.23). We noted no difference for symptomatic intracranial haemorrhage between
      groups (4 [1%] vs 6 [1%], respectively; p=0.55); the rate of major extracranial
      bleeding was higher with enoxaparin than with unfractionated heparin (7 [1%] vs
      0; p=0.015). INTERPRETATION: Our results suggest that for patients with acute
      ischaemic stroke, enoxaparin is preferable to unfractionated heparin for venous
      thromboembolism prophylaxis in view of its better clinical benefits to risk ratio
      and convenience of once daily administration.

PMID- 17448821
TI  - Protective efficacy of a monovalent oral type 1 poliovirus vaccine: a case
      control study.
AB  - BACKGROUND: A high-potency monovalent oral type 1 poliovirus vaccine (mOPV1) was
      developed in 2005 to tackle persistent poliovirus transmission in the last
      remaining infected countries. Our aim was to assess the efficacy of this vaccine
      in India. METHODS: We estimated the efficacy of mOPV1 used in supplementary
      immunisation activities from 2076 matched case-control pairs of confirmed cases
      of poliomyelitis caused by type 1 wild poliovirus and cases of non-polio acute
      flaccid paralysis in India. The effect of the introduction of mOPV1 on population
      immunity was calculated on the basis of estimates of vaccination coverage from
      data for non-polio acute flaccid paralysis. FINDINGS: In areas of persistent
      poliovirus transmission in Uttar Pradesh, the protective efficacy of mOPV1 was
      estimated to be 30% (95% CI 19-41) per dose against type 1 paralytic disease,
      compared with 11% (7-14) for the trivalent oral vaccine. 76-82% of children aged
      0-23 months were estimated to be protected by vaccination against type 1
      poliovirus at the end of 2006, compared with 59% at the end of 2004, before the
      introduction of mOPV1. INTERPRETATION: Under conditions where the efficacy of
      live-attenuated oral poliovirus vaccines is compromised by a high prevalence of
      diarrhoea and other infections, a dose of high-potency mOPV1 is almost three
      times more effective against type 1 poliomyelitis disease than is trivalent
      vaccine. Achieving high coverage with this new vaccine in areas of persistent
      poliovirus transmission should substantially improve the probability of rapidly
      eliminating transmission of the disease.

PMID- 17448822
TI  - Eradication versus control for poliomyelitis: an economic analysis.
AB  - BACKGROUND: Worldwide eradication of wild polioviruses is likely to yield
      substantial health and financial benefits, provided we finish the job. Challenges
      in the four endemic areas combined with continuing demands for financial
      resources for eradication have led some to question the goal of eradication and
      to suggest switching to a policy of control. METHODS: We developed a dynamic
      model, based on modelling of the currently endemic areas in India, to show the
      importance of maintaining and increasing the immunisation intensity to complete
      eradication and to illustrate how policies based on perception about high short
      term costs or cost-effectiveness ratios without consideration of long-term
      benefits could undermine any eradication effort. An extended model assesses the
      economic implications and disease burden of a change in policy from eradication
      to control. FINDINGS: Our results suggest that the intensity of immunisation must
      be increased to achieve eradication, and that even small decreases in intensity
      could lead to large outbreaks. This finding implies the need to pay even higher
      short-run costs than are currently being spent, which will further exacerbate
      concerns about continued investment in interventions with high perceived cost
      effectiveness ratios. We show that a wavering commitment leads to a failure to
      eradicate, greater cumulative costs, and a much larger number of cases. We
      further show that as long as it is technically achievable, eradication offers
      both lower cumulative costs and cases than control, even with the costs of
      achieving eradication exceeding several billion dollars more. A low-cost control
      policy that relies only on routine immunisation for 20 years with discounted
      costs of more than $3500 million could lead to roughly 200 000 expected paralytic
      poliomyelitis cases every year in low-income countries, whereas a low-case
      control policy that keeps the number of cases at about 1500 per year could cost
      around $10 000 million discounted over the 20 years. INTERPRETATION: Focusing on
      the large costs for poliomyelitis eradication, without assessing the even larger
      potential benefits of eradication and the enormous long-term costs of effective
      control, might inappropriately affect commitments to the goal of eradication, and
      thus debate should include careful consideration of the options.

PMID- 17448823
TI  - Treating excessive sweating with poison.

PMID- 17448824
TI  - Oslo Ministerial Declaration--global health: a pressing foreign policy issue of
      our time.
AB  - Under their initiative on Global Health and Foreign Policy, launched in
      September, 2006, in New York, the Ministers of Foreign Affairs of Brazil, France,
      Indonesia, Norway, Senegal, South Africa, and Thailand issued the following
      statement in Oslo on March 20, 2007-In today's era of globalisation and
      interdependence there is an urgent need to broaden the scope of foreign policy.
      Together, we face a number of pressing challenges that require concerted
      responses and collaborative efforts. We must encourage new ideas, seek and
      develop new partnerships and mechanisms, and create new paradigms of cooperation.
      We believe that health is one of the most important, yet still broadly neglected,
      long-term foreign policy issues of our time. Life and health are our most
      precious assets. There is a growing awareness that investment in health is
      fundamental to economic growth and development. It is generally acknowledged that
      threats to health may compromise a country's stability and security. We believe
      that health as a foreign policy issue needs a stronger strategic focus on the
      international agenda. We have therefore agreed to make impact on health a point
      of departure and a defining lens that each of our countries will use to examine
      key elements of foreign policy and development strategies, and to engage in a
      dialogue on how to deal with policy options from this perspective. As Ministers
      of Foreign Affairs, we will work to: increase awareness of our common
      vulnerability in the face of health threats by bringing health issues more
      strongly into the arenas of foreign policy discussions and decisions, in order to
      strengthen our commitment to concerted action at the global level; build
      bilateral, regional and multilateral cooperation for global health security by
      strengthening the case for collaboration and brokering broad agreement,
      accountability, and action; reinforce health as a key element in strategies for
      development and for fighting poverty, in order to reach the Millennium
      Development Goals; ensure that a higher priority is given to health in dealing
      with trade issues and in conforming to the Doha principles, affirming the right
      of each country to make full use of TRIPS flexibilities in order to ensure
      universal access to medicines; strengthen the place of health measures in
      conflict and crisis management and in reconstruction efforts. For this purpose,
      we have prepared a first set of actionable steps for raising the priority of
      health in foreign policy in an Agenda for Action. We pledge to pursue these
      issues in our respective regional settings and in relevant international bodies.
      We invite Ministers of Foreign Affairs from all regions to join us in further
      exploring ways and means to achieve our objectives.

PMID- 17448825
TI  - Ankylosing spondylitis.
AB  - Ankylosing spondylitis is a common inflammatory rheumatic disease that affects
      the axial skeleton, causing characteristic inflammatory back pain, which can lead
      to structural and functional impairments and a decrease in quality of life. New
      imaging techniques and therapies have substantially changed the management of
      this disease in the past decade. Whether inhibition of radiographic progression
      and structural damage can be reached with available drugs is as yet unclear.
      Furthermore, treatment with non-steroidal anti-inflammatory agents and
      physiotherapy remains an important approach to long-term management of patients
      with ankylosing spondylitis. The new treatment options with tumour necrosis
      factor blockers seems a breakthrough for patients refractory to conventional
      treatment.

PMID- 17448827
TI  - Reversal of coma with an injection of glue.

PMID- 17448826
TI  - Interventions to reduce harm associated with adolescent substance use.
AB  - A major proportion of the disease burden and deaths for young people in developed
      nations is attributable to misuse of alcohol and illicit drugs. Patterns of
      substance use established in adolescence are quite stable and predict chronic
      patterns of use, mortality, and morbidity later in life. We integrated findings
      of systematic reviews to summarise evidence for interventions aimed at prevention
      and reduction of harms related to adolescent substance use. Evidence of efficacy
      was available for developmental prevention interventions that aim to prevent
      onset of harmful patterns in settings such as vulnerable families, schools, and
      communities, and universal strategies to reduce attractiveness of substance use.
      Regulatory interventions aim to increase perceived costs and reduce availability
      and accessibility of substances. Increasing price, restricting settings of use,
      and raising legal purchase age are effective in reducing use of alcohol and
      tobacco and related harms. Screening and brief intervention are efficacious, but
      efficacy of a range of treatment approaches has not been reliably established.
      Harm-reduction interventions are effective in young people involved in risky and
      injecting substance use.

PMID- 17448828
TI  - Ally the future: building relationships that build the future of oral and
      maxillofacial surgery.

PMID- 17448829
TI  - A protocol for the management of frontal sinus fractures emphasizing sinus
      preservation.
AB  - PURPOSE: The purpose of this retrospective study is to review the incidence and
      etiology of frontal sinus fractures at an urban trauma center and validate a
      treatment protocol by assessing the outcome of a consecutive series of patients
      treated over a 10-year period. PATIENTS AND METHODS: All patients with frontal
      sinus fractures admitted to our trauma service from 1995 to 2005 were managed by
      the same surgeons using similar treatment philosophies based on the amount of
      displacement or comminution of the anterior and/or posterior table, the integrity
      of the nasofrontal duct, and the neurologic status of the patient as determined
      by clinical and radiographic examination. Using information obtained from the
      Trauma Registry and from individual physician chart notes, a database was created
      for the purpose of assessing outcome, defined as complications, length of
      hospital stay, and death. Demographics, injury severity score, fracture pattern,
      mechanism of injury, length of hospital stay, the number of operations,
      concomitant maxillofacial injuries, treatment, follow-up, and complications were
      statistically described. Outcome measures were evaluated by Student's t test
      using continuous variables. RESULTS: One thousand two hundred seventy-five
      patients with facial fractures were identified during the study period, of which
      144 patients (11.3%) carried the diagnosis of frontal sinus fracture; 28 patients
      had inadequate records, leaving a study group of 116 patients. The majority of
      patients were male, had a mean age of 33.7 years, and presented with significant
      injuries demonstrated by a mean injury severity score of 23.7 and mean length of
      hospital stay of 8.9 days. The most common mechanisms of injury were blunt trauma
      resulting from a motor vehicle collision, fall, assault, or other accidents.
      Sixty-six patients presented with nondisplaced frontal sinus fractures that were
      managed nonoperatively; 50 patients had frontal sinus injuries that required
      surgical repair consisting of: 1) open reduction and internal fixation of the
      anterior table alone, with preservation of the sinus membrane (n = 29); 2)
      removal of all sinus mucosa, obliteration of the frontal sinus with autogenous
      abdominal fat, and reconstruction of the anterior table (n = 5); and 3) removal
      of all sinus mucosa, cranialization of the frontal sinus, and lining of the
      nasofrontal recess with a pericranial flap (n = 16). Six patients died of
      concomitant injuries. With follow-up ranging between 0 and 90 weeks, there were
      no known complications in the patients treated nonoperatively; 82% of the
      patients maintained normal sinus function and anatomy and the overall
      complication rate was 6.9%. Complications occurred in 16% of those patients
      treated surgically: including brain abscess, contour deformity, osteomyelitis,
      hematoma, meningitis, and mucocele. There was no statistically significant
      association between complications and other patient variables (P > .05), other
      than the test for injury severity score, which was different between survivors
      and nonsurvivors (P < .01). CONCLUSION: Application of the management protocol
      described in this report results in functional sinus preservation for the
      majority of patients, with relatively few significant perioperative
      complications.

PMID- 17448830
TI  - Manipulating the mandibular distraction site at different stages of
      consolidation.
AB  - PURPOSE: The purpose of this study was to define optimal timing and conditions
      for correcting an open bite side effect by manipulating the distraction site with
      orthodontic springs after mandibular distraction. MATERIALS AND METHODS: At 0, 1,
      2, 3, and 8 weeks postdistraction, interarch springs were attached for 2 weeks to
      close distraction-produced open bites in 45 rabbits. Distractors were removed in
      half of the animals receiving spring treatment. Segment position was recorded by
      weekly direct measurements and radiographs. Tissue samples were collected at the
      end of spring application for microcomputerized tomography analysis and
      measurements of lateral symmetry. RESULTS: Orthodontic springs closed the open
      bite with or without distractors in place immediately after distraction and
      partially corrected the bite at later stages of bone consolidation. Distractor
      removal produced more rapid bite closure but also introduced lateral buckling of
      the distraction site during early consolidation. The lateral buckling was not
      observed if springs were applied after 2 weeks of consolidation. The amount of
      bite correction with orthodontic springs correlated with mineralization of the
      distraction site. CONCLUSION: During the consolidation period, a distraction site
      can be callus manipulated with orthodontic springs to correct an open bite. The
      amount of correction depended on when springs were placed and whether distractors
      were removed at the time of spring application.

PMID- 17448831
TI  - Biological assessment of porous-implant hydroxyapatite combined with periosteal
      grafting in maxillary defects.
AB  - PURPOSE: To investigate the use of porous hydroxyapatite (HA) combined with
      periosteal graft to repair an induced maxillary bone defect. MATERIALS AND
      METHODS: A defect was produced in the premaxillary bone of rats. Four groups were
      used: 1) those treated with the mucoperiosteal graft from the premaxilla; 2)
      those treated with HA combined with mucoperiosteal graft from the premaxilla; 3)
      those treated with HA combined with periosteal graft from the femur; and 4) those
      treated with periosteal graft from the femur. RESULTS: The radiographic aspects
      from all groups showed no signs of bone formation after 2 weeks. After 16 weeks,
      there was evidence of points of radiolucency inside the HA implants. Cell
      proliferation occurred from the periosteum covering the defect. Bone tissue grew
      from the defect margin to inside the defect in all cases. Mature bone was seen
      around the HA implants after 8 and 16 weeks. CONCLUSION: The periosteal graft
      provides satisfactory support to the HA implant, allowing the growth of new bone.

PMID- 17448832
TI  - Treatment of mucocele of the lower lip with carbon dioxide laser.
AB  - PURPOSE: The aim of this report was to evaluate the outcome and complications of
      the treatment of numerous patients with mucoceles of lower lip by means of CO(2)
      laser vaporization. MATERIALS AND METHODS: This study included 82 patients with
      biopsy-confirmed mucocele of the lower lip who were treated with CO(2) laser
      vaporization from January 1999 to December 2003; the data on recurrence and
      complications were collected. RESULTS: There was a recurrence in 2 cases.
      Complications were rare, except for mild discomfort. One patient felt temporary
      numbness at the operative site. There was no bleeding and minimal scar formation.
      CONCLUSION: CO(2) laser vaporization to treat the mucocele of the lower lip is
      effective and has few complications. Because the operative time is shorter than
      with the excisional method, it is especially good for children and for less
      cooperative patients with this lesion.

PMID- 17448833
TI  - Accuracy of using the antilingula as a sole determinant of vertical ramus
      osteotomy position.
AB  - PURPOSE: The antilingula is an important landmark in mandibular ramus surgery.
      Its relationship to the lingula provides useful clinical information as to the
      position of the mandibular foramen and inferior alveolar nerve. The purpose of
      this study was to determine the reliability of using the antilingula as a guide
      to osteotomy placement for intraoral vertical ramus osteotomies. MATERIALS AND
      METHODS: Eighteen cadaver mandibles were harvested and the antilingula was
      identified on each hemimandible by palpating the most prominent bulge on the
      lateral aspect of the mandible. In addition, the lingula (the entrance of the
      mandibular neurovascular bundle into the medial aspect of the ascending ramus of
      the mandible) was identified. A 1 mm fissure bur was used to drill a hole
      perpendicular to bone, from the deepest aspect of the concavity at the center of
      the lingula. The drill perforated both the medial and lateral cortices of the
      mandible. The distance from the antilingula to lingula was measured and recorded
      in both the anterior-posterior and the superior-inferior planes. RESULTS: There
      was complete concordance of the position of the lingula and antilingula in the
      anterior-posterior dimension in 11.1% of the specimens. In 33% of the specimens,
      the lingula was found anterior to the antilingula and in 45.6% the lingula was
      found posterior to the antilingula. There was complete concordance of the lingula
      and antilingula in the superior-inferior dimension in 2.8% of specimens. The
      lingula was found superior to the antilingula in 47.2% of the specimens and
      inferior to the antilingula in 50% of samples. CONCLUSION: In most instances, the
      position of the lingula was posterior-inferior relative to the position of the
      antilingula. At a measurement of 5 mm posterior to the antilingula (at the level
      of the antilingula), there was no risk of damaging the neurovascular bundle in
      this cadaveric study.

PMID- 17448834
TI  - The submental flap in facial reconstruction: advantages and limitations.
AB  - PURPOSE: Complex defects resulting from surgical excision of facial cancer
      sometimes require reconstruction using microvascular free tissue transfer. Tissue
      transfer from areas distant from the face can resolve many problems, but often
      provides a poor cosmetic match with facial skin. The submental flap helps
      surmount this problem. Cervical skin has similarities with face skin, and because
      this is a regional flap, it helps eliminate microsurgical risks. In this article
      we present a series of 9 cases, review the anatomy and the surgical technique,
      and explain the advantages and limitations of the submental flap. PATIENTS AND
      METHODS: A successive series of 9 patients in which this reconstruction was
      performed was reviewed retrospectively, and the results were analyzed. RESULTS:
      Submental flap facial reconstruction was performed on 9 patients (8 men and 1
      woman) between 1993 and 2004. Mean patient age was 53.6 years (range, 43 to 81
      years). Eight of the 9 external skin coverage cases were associated with excision
      of cutaneous malignancies; 1 case involved treatment of burn sequelae. There were
      no cases of marginal mandibular nerve palsy. In 6 cases, venous drainage was
      disrupted after raising the flap, but without causing flap loss. This disruption
      was overcome in 4 to 5 days without the need for flap revision or any other
      interventions. Partial loss of the distal extent of the flap occurred in 2 cases.
      In all cases, moderately good skin color and texture match was achieved.
      Debulking of the flap was needed in 6 cases. The donor site recovered well with
      no hypertrophic scarring and no restriction to neck movement. CONCLUSIONS: The
      submental artery island flap is a useful reconstructive procedure that offers
      options to the reconstructive surgeon and has definite advantages over distant
      flaps in terms of ease of dissection and donor site appearance.

PMID- 17448835
TI  - Clinical and histopathologic study of the use of gangliosides for nerve
      regeneration in rats after axonotmesis.
AB  - PURPOSE: This study involved a clinical and histopathologic evaluation of the use
      of gangliosides in nerve regeneration, using an experimental model with higher
      vertebrates. MATERIALS AND METHODS: Forty Sprague Dawley rats had their right
      sciatic nerve crushed for 1 minute in a hemostatic tweezer. The animals were
      divided into experimental and control groups. The animals in the experimental
      group received an intramuscular injection of gangliosides in the left thigh for
      25 days, whereas those in the control group received infiltrations of distilled
      water. A clinical evaluation of gait was made 24 hours and then 45 days after the
      surgical intervention, and a histopathologic evaluation of the sciatic nerves was
      performed after 45 days. RESULTS: There were no signs that the use of
      gangliosides significantly altered the animals' gait after 45 days. The animals
      in the experimental group had a greater frequency and intensity of inflammatory
      response than seen in the control group. CONCLUSION: The systemic use of
      gangliosides produced no improvement in gait and led to a more frequent and
      intense inflammatory response at the site of injury.

PMID- 17448836
TI  - Odontogenic tumors in Sri Lanka: analysis of 226 cases.
AB  - PURPOSE: The purpose of this study was to analyze the relative prevalence of
      odontogenic tumors in Sri Lanka and compare it with prevalences reported for
      other countries. PATIENTS AND METHODS: A total of 226 cases of odontogenic tumors
      reported by the Department of Oral Pathology, Faculty of Dental Sciences,
      University of Peradeniya between 1996 and 2002, were analyzed. RESULTS: The most
      prevalent tumor was ameloblastoma (69.8%); odontoma was the fourth most prevalent
      (4.5%). No gender predilection was seen, but the tumors occurred most frequently
      in the second to fifth decades of life (77.4%) and most commonly in the mandible
      (79.6%). CONCLUSIONS: The comparative data with statistically significant
      differences suggest a geographical difference in the relative prevalence of
      ameloblastoma among various continents. It is suggested that ameloblastoma most
      frequently occurs in the mandible (the posterior region) in all Asian, African,
      and South American countries.

PMID- 17448837
TI  - Immediate reconstruction of mandibular defects: a retrospective report of 242
      cases.
AB  - PURPOSE: This study was conducted to evaluate the effects of routine protocols in
      immediate mandibular reconstruction. PATIENTS AND METHODS: A total of 242
      patients who underwent immediate mandibular reconstruction were reviewed
      retrospectively. The therapeutic evaluation was performed according to outcomes
      of clinical and radiographic examination. The evaluated contents included facial
      symmetry, degree of mouth opening, occlusal relationship, and temporomandibular
      joint symptoms. Statistical analysis was also carried out to compare therapeutic
      differences between different methods for mandibular reconstruction. SPSS 10.0
      for Windows was used for statistical analysis. RESULTS: The follow-up showed
      satisfactory long-term outcome in 203 patients. Statistical analysis revealed no
      significant difference in restoration of facial contour among several groups
      (chi(2) 0.05(15) = 21.93; P = .109 > .05). Ten cases involved serious
      postoperative complications, including local infection, exposure of rigid
      fixation plate, and serious pain. CONCLUSIONS: Our findings indicate that
      autogenous bone graft is the best for reconstruction of small mandibular defects.
      Frozen autogenous lesional mandible plus autogenous iliac or rib graft is
      recommended for reconstruction of large defects in the mandible. Strict patient
      selection, careful surgical procedure, and appropriate preoperative and
      postoperative nursing care are key factors in successful transplantation.

PMID- 17448838
TI  - Psychological complications of maxillofacial trauma: preliminary findings from a
      Nigerian university teaching hospital.
AB  - PURPOSE: This study sought to determine 1) the prevalence of psychological
      distress in a series of subjects who sustained maxillofacial injuries and 2)
      temporal changes in psychological functioning over 12 weeks compared with
      baseline values. PATIENTS AND METHODS: This was a prospective, repeated-measures
      design study of consecutively recruited subjects at a Nigerian university
      teaching hospital. A total of 51 subjects with facial injuries had repeated
      follow-up assessments (10 days, 6 to 8 weeks, and 10 to 12 weeks) after the
      trauma, using standard instruments. RESULTS: The General Health Questionnaire
      identified a high prevalence of psychological morbidity in the subjects (90%),
      with 41.2% and 11.8% scoring above threshold values on the hospital anxiety and
      depression scales, respectively. Five subjects satisfied the criteria on the
      Trauma Screening Questionnaire for a diagnosis of post-traumatic stress disorder
      during the follow-up period. Psychological distress (General Health Questionnaire
      caseness) remained at high levels during the 2 follow-up assessments.
      CONCLUSIONS: The management of facial injuries should integrate a
      multidisciplinary approach that addresses the psychological needs of the patients
      in both the short term and the long term.

PMID- 17448839
TI  - The superiorly based platysma flap for oral reconstruction in conjunction with
      neck dissection: a case series.
AB  - PURPOSE: The purpose of this study was to access the reliability and use of the
      superiorly based platysma flap for reconstruction of small and medium oral
      defects. PATIENTS AND METHODS: This case series consists of 5 patients who were
      reconstructed with a superiorly based platysma flap for defects of the following
      oral region: buccal mucosa, floor of the mouth, and lateral gingiva. The flaps
      were monitored for complications, including skin loss and ischemia in the
      postoperative period. RESULTS: Three patients (60%) had some skin sloughing in
      the recipient site. None of the patients had complications in the donor site.
      CONCLUSION: The superiorly based platysma flap can survive after the facial
      artery has been ligated, which is the normal procedure during neck dissection. If
      skin sloughing occurs, it is usually inconsequential for intraoral reconstruction
      because the underlying muscle remains viable and undergoes epithelialization.

PMID- 17448840
TI  - Assessing postoperative discomfort after third molar surgery: a prospective
      study.
AB  - PURPOSE: The purpose of this study was to identify the risk factors for severe
      discomfort after mandibular third molar surgery and to assess the validity of the
      Postoperative Symptom Severity (PoSSe) scale. PATIENTS AND METHODS: In a 2-year
      prospective study, a total of 255 unilateral impacted mandibular third molar
      teeth were surgically removed under local anesthesia by 3 surgeons. Standardized
      surgical and analgesic protocols were followed. At the review appointment, 1 week
      after surgery, all patients returned a completed follow-up questionnaire (PoSSe
      scale) and were evaluated clinically for postoperative pain (number of
      painkillers taken) and trismus (differences in mouth opening). Sixteen predictive
      variables were evaluated using stepwise logistic regression analysis to identify
      the risk factors associated with severe discomfort. RESULTS: Severe postoperative
      discomfort was predicted by these independent variables: gender, tobacco use,
      ramus relationship/space available, and antibiotic prophylaxis. Oral
      contraceptive use and operation time were not identified as risk factors. The
      patients' perceptions of the severity of symptoms (PoSSe scale score) was
      strongly correlated with clinical assessment of trismus (r = 0.54) and pain (r =
      0.42). CONCLUSION: The PoSSe scale resulted in a valid and responsive measure of
      the severity of symptoms after surgical extraction of lower third molars and
      reflected the clinical severity of the postoperative discomfort. From a patient's
      perspective, operative factors had little bearing on the quality of life after
      removal of mandibular third molars.

PMID- 17448841
TI  - Simple bone cyst of the jaws: evaluation of treatment outcome by review of 132
      cases.
AB  - PURPOSE: To estimate the prognosis of simple bone cyst of the jaws. SUBJECTS AND
      METHODS: We reviewed 132 of our own and published cases that received
      postoperative follow-up until healing or recurrence. The recurrence rate was
      obtained from treatment outcomes. The time to healing or recurrence was estimated
      from the distributions of the times of examinations that confirmed healing or
      recurrence. RESULTS: Simple bone cyst lesions healed in 98 cases and recurred in
      34 cases. The overall recurrence rate was 26%. The recurrence rate was 71% and
      75% for cases with multiple cysts and cemento-osseous dysplasia, respectively. In
      most cases, healing or recurrence was confirmed within 3 years, 5 months of
      surgery. The maximum number of cases with healing and recurrence was observed 12
      to 17 months and 2 to 2.5 years after surgery, respectively. CONCLUSION: The
      recurrence rate was higher than rates reported previously. We recommend that
      postoperative examination be continued until complete healing is confirmed
      radiographically, particularly in cases with multiple lesions or cemento-osseous
      dysplasia. Healing or recurrence should be confirmed within 3 years of treatment.

PMID- 17448842
TI  - Biomechanical testing of different osteosynthesis systems for segmental resection
      of the mandible.
AB  - PURPOSE: This investigation assessed the mechanical behavior of 3 different
      locking and nonlocking reconstruction systems-Unilock 2.4, Reconstruction 2.4,
      and Reconstruction 2.7-with regard to plate and screw fracture. MATERIALS AND
      METHODS: Five different plate/screw configurations (Unilock 2.4-locking screws,
      Unilock 2.4 -conventional screws, Reconstruction 2.4-conventional screws,
      Reconstruction 2.7-conventional screws, and Unilock 2.4-locking screws with a 1
      mm gap; Synthes, Umkirch, Germany) were tested on synthetic mandibles. All
      mandibles were resected on the left side between the canine and third molar,
      reconstructed, and loaded cyclically between 30 and 300 N up to 250,000 cycles or
      until screw or plate failure occurred. RESULTS: No screw fractures were observed.
      All plates fractured close to the distal fragment. The Unilock plates fixed with
      locking screws withstood significantly more cycles until failure than the
      Reconstruction plates 2.4 fixed with conventional MF-Cortex screws. No
      significant differences were found in the other groups. Only 2 of the 34 plates
      tested, both of the Reconstruction 2.7 system, reached the runout limit.
      CONCLUSIONS: Unilock plates fixed with locking screws have a higher long-term
      stability than the Reconstruction 2.4 system. A 1-mm gap between the plate and
      mandible does not lead to early screw failure in the Unilock 2.4 system with
      locking screws. The Reconstruction 2.7 system seems superior if well contoured,
      because 2 of those plates reached the runout limit; however, this system is not
      as easy to handle as the 2.4 systems, and good contouring is difficult to
      achieve. Therefore, we consider the Unilock 2.4 system with locking screws the
      best choice.

PMID- 17448843
TI  - Prospective study of periapically infected teeth treated with periapical surgery
      including ultrasonic preparation and retrograde intermediate restorative material
      root-end fillings.
AB  - PURPOSE: The aim of this prospective study was to evaluate the current method of
      periapical surgery at the Maxillofacial Unit, Halmstad Hospital, which included
      ultrasonic root-end preparation and the use of intermediate restorative material
      as a root-end filling material. PATIENTS AND METHODS: Fifty-five consecutive
      patients with a total of 56 treated teeth, within the close vicinity of the
      hospital, were included in the study during a period of 10 months in 2002. Teeth
      with advanced periodontal bone loss or presence of root fractures were excluded
      from the study. RESULTS: All teeth but 1 were followed up after 1 year (12-19
      months). Radiological evaluation (complete or incomplete healing) and clinical
      examination showed an 80% success rate. Twenty percent of the patients were
      stated as failures (uncertain healing and unsatisfactory healing). The success
      rate was highest among incisors (100%) and lowest among molars and premolars (78%
      and 69%, respectively). CONCLUSION: Compared with other studies, these findings
      seemed to be a bit inferior regarding success rate. However, our study population
      was not selected for the study purpose but rather represented the true clinical
      variety taken care of in our practice.

PMID- 17448844
TI  - Nitrous oxide does not aggravate postoperative emesis after orthognathic surgery
      in female and nonsmoking patients.
AB  - PURPOSE: The purpose of this study was to evaluate the effect of supplemental
      nitrous oxide on postoperative nausea and vomiting (PONV) after propofol
      anesthesia for orthognathic surgery in female and nonsmoking patients. PATIENTS
      AND METHODS: We compared PONV in 28 ASA-I female nonsmoking patients undergoing
      orthognathic surgery. Anesthesia was induced with propofol combined with
      fentanyl, and tracheal intubation was facilitated with vecuronium. Anesthesia was
      maintained with propofol with or without nitrous oxide. No patient received
      neostigmine. PONV was assessed as score 0 (no PONV), score 1 (nausea), and score
      2 (vomiting) during the 24-hour recovery period. RESULTS: There were no
      differences in the patients' characteristics, operation, anesthesia and emergence
      time, fluid transfusion, blood loss, urine output, and total propofol and
      fentanyl doses between the 2 groups. There was also no difference in PONV score
      in 2 groups. Only 1 patient in each group vomited. CONCLUSIONS: It is suggested
      that supplemental nitrous oxide does not aggravate PONV after propofol anesthesia
      for orthognathic surgery in female nonsmoking patients.

PMID- 17448845
TI  - Integrity of craniofacial plating systems after multiple sterilization
      procedures.
AB  - PURPOSE: To determine the effect of multiple autoclave sterilization cycles on
      the integrity of titanium plates and screws used in craniofacial reconstruction.
      MATERIALS AND METHODS: Torque to fracture was evaluated for 36 titanium 6AL-4V
      (Ti 6/4) screws divided evenly into 3 groups and tested as machined (control),
      after 10 cycles of autoclaving or after 50 cycles of autoclaving. Sterilization
      was carried out by autoclaving for 15 minutes followed by 8 minutes of drying at
      270 degrees to 272 degrees F. The maximum torque attained before fracture was
      recorded. Rotating beam specimens were crafted from single lots of Ti 6/4,
      commercially pure titanium grade 4 (CP4) and commercially pure titanium grade 2
      (CP2), and then subjected to testing in a standard rotating beam device as
      machined (control), after 10 cycles of autoclaving or after 50 cycles of
      autoclaving. The cycles required to fracture the specimen at a given applied
      stress were recorded for each material and for the number of autoclavings carried
      out before testing. RESULTS: Although there was a trend toward decreased strength
      and increased ability to fracture with increased number of autoclave cycles, this
      did not reach statistical significance. Torque to fracture testing for 7 mm Ti
      6/4 screws showed no significant difference in the maximum torque reached before
      fracture between controls, those screws that had been autoclaved 10 times (P <
      .500 +/- 5.70) and those that had been autoclaved 50 times (P < .398 +/- 4.08).
      Rotating beam specimens of Ti 6/4, CP4, and CP2 showed no significant difference
      in cycles to fracture regardless of the number of sterilization cycles to which
      the material was subjected. CONCLUSIONS: Repeated cycles of autoclaving had no
      significant effect on the integrity of titanium plates and screws routinely used
      in craniofacial surgery.

PMID- 17448846
TI  - Do magnetic resonance imaging and ultrasound add anything to the preoperative
      workup of parotid gland tumors?
AB  - PURPOSE: To assess the additional value of magnetic resonance imaging (MRI) and
      ultrasound (US) to physical examination (PE) and fine needle aspiration cytology
      (FNAC) in the preoperative determination of the location and histology of parotid
      gland tumors. PATIENTS AND METHODS: Prospectively, 99 patients with 77 benign and
      22 malignant lesions were included; 82 underwent parotidectomy. FNAC was
      performed in 88 patients. On PE, the location of the tumor was predicted. Eighty
      nine patients had MRI and 47 US. Various characteristics and the presumed
      diagnosis were assessed. Furthermore, the location of the tumor in relation to
      the facial nerve was predicted. The results were compared with the definite
      histology and the location during surgery. RESULTS: Of the MRI characteristics,
      incomplete demarcation from normal parotid gland tissue showed the highest
      positive predictive value (PPV) for malignancy of 0.48. Of the US
      characteristics, enlarged lymph nodes yielded the highest PPV for malignancy of
      0.5. Cytology correctly predicted the benign or malignant nature of the tumor in
      all cases. Superficial location was well predicted on PE with a PPV of 0.8,
      slightly better on MRI (PPV of 0.87), and worse on US (PPV of 0.7). CONCLUSION:
      FNAC is the only accurate investigation for classifying a parotid gland tumor as
      benign or malignant. Palpation and MRI are superior to US in predicting tumor
      location. Because the results for palpation and MRI are almost equal, MRI should
      only be reserved for specific cases, and not routinely requested.

PMID- 17448847
TI  - Submandibular gland excision: 15 years of experience.
AB  - PURPOSE: The surgical management of submandibular gland diseases has always been
      a challenge because it carries a considerable risk of nerve injury. The aim of
      this study was to review a single institution's experience of a nonselected case
      series of submandibular gland excision over 15 years. MATERIALS AND METHODS: We
      retrospectively analyzed 258 unselected submandibular excisions of a tertiary
      university center for the histopathologic diagnosis and postoperative morbidity;
      119 patients (46%) with sialolithiasis, 88 patients (34%) with sialadenitis, and
      51 patients (20%) with submandibular tumors were operated. RESULTS: We found a
      high rate of malignant tumors (42%) in the group of submandibular gland tumors. A
      low rate of transient palsies of the mandibular branch of the facial nerve (9%)
      and lingual nerve (2%) was observed. One patient developed a permanent paresis of
      the mandibular branch (<1%). CONCLUSION: Our large series has shown that
      standardized submandibular sialadenectomy is a safe operation with a low rate of
      complications. Malignant disease is frequent in tumors of the submandibular
      gland.

PMID- 17448848
TI  - Risk indicators for third molar caries and periodontal disease in senior adults.
AB  - PURPOSE: This study was designed to identify risk indicators for the prevalence
      at enrollment and incidence over 36 months of periodontal pathology and coronal
      caries experience affecting third molars in a community-based study of people
      over 65 years of age. SUBJECTS AND METHODS: Data from a subsample of 810 dentate
      subjects from the Piedmont 65+ Study were available for analyses. All visible
      teeth were examined. Periodontal probing measures were taken at 2 sites,
      mesiobuccal and buccal/facial. Clinical data on caries experience were collected
      by visual-tactile examination. At enrollment, 340 subjects had at least 1 visible
      third molar; all were examined for caries experience. Periodontal probing
      measures were available for 277 of these same subjects. The significance of the
      possible risk indicators for periodontal pathology and caries affecting third
      molars was determined by chi(2) tests. Statistical significance was set at .05.
      Logistic multivariable models were used to derive odds ratios and 95% confidence
      intervals. RESULTS: African-American subjects were more likely to have visible
      third molars (P < .01). Caucasian subjects were more likely to have third molar
      coronal caries experience (P < .01), as were subjects with greater than a high
      school education and those with a dental visit within 3 years (both P < .01).
      However, African American subjects were more likely to have periodontal
      pathology, CALs >/= 3 mm on third molars (P < .01), as were those who used
      tobacco (P < .01). None of the other risk indicators we studied were associated
      with progression of periodontal pathology or coronal caries experience on visible
      third molars. CONCLUSION: In this population study of senior adults, Caucasians
      and African Americans appear to have different levels of risk for caries
      experience and periodontal pathology affecting retained third molars.

PMID- 17448849
TI  - A new 3-dimensional plate for transoral endoscopic-assisted osteosynthesis of
      condylar neck fractures.
AB  - PURPOSE: Transoral surgical treatment of condylar neck fractures minimizes the
      risk of damaging the facial nerve. But fracture reduction and plate
      osteosynthesis remain challenging, especially when using 2 plates, although
      endoscopic assistance has proven helpful. To further improve and simplify
      osteosynthesis at the condylar neck, a new delta-shaped osteosynthesis plate that
      mimics the function of 2 plates has been developed. The present clinical follow
      up study was conducted to evaluate this new plate. PATIENTS AND METHODS: A total
      of 16 patients with 19 condylar neck fractures (3 Spiessl I, 13 Spiessl II, 1
      Spiessl III, 2 Spiessl IV) and 3 bilateral fractures were treated through an
      endoscopic-assisted transoral approach. After reduction, the plate was applied,
      with the screws inserted either transcutaneously or with angulated instruments.
      RESULTS: The operation time ranged between 55 and 120 minutes. More than 6 months
      after the operation, functional parameters returned to normal, with an average
      mouth opening of 41 mm, protrusion of 5 mm, and laterotrusion of 6 mm.
      Radiographic controls showed good fracture alignment in 15 of 19 cases
      immediately after the operation, and in 14 of 19 cases 6 months after the
      operation. No plate fracture or bending was observed. In 3 patients, loose screws
      were found on plate removal. CONCLUSIONS: The clinical data and the engineering
      and biomechanical background suggest that the new delta-shaped plate can be
      regarded as 2 miniplates. The new plate is suitable for treatment of condylar
      neck fractures, particularly when used in an endoscopic-assisted transoral
      approach.

PMID- 17448850
TI  - Prospective study of facial nerve function after surgical procedures for the
      treatment of temporomandibular pathology.
AB  - PURPOSE: The aim of this prospective study was to report facial nerve injury
      following surgical procedures for the treatment of temporomandibular pathology,
      using the House-Brackmann facial nerve grading system (HBFNGS) as a means of
      classifying and measuring the degree and type of injury. PATIENTS AND METHODS:
      The sample consisted of 32 patients who underwent temporomandibular joint (TMJ)
      surgery. A total of 50 approaches were carried out. Surgical procedures consisted
      of TMJ reconstruction, gap arthroplasty, eminectomy, bone plates for the
      treatment of chronic mandibular luxation, and disc plication. Facial nerve
      function of all patients was evaluated preoperatively and 24 hours after surgery.
      Patients who presented postoperative facial nerve injury were likewise examined
      using the HBFNGS at 24 hours, 1 week, 1 month, and 3 months. RESULTS: Of the 32
      patients, 12.5% (ie, 8% of the 50 approaches) showed signs of facial nerve injury
      after TMJ surgery. The prevalence of postoperative facial nerve injury was
      significantly greater in the patients who had ankylosis (P = .014) and in those
      submitted to gap arthroplasty (P = .011). At 24 hours, none of the patients
      showed total nerve paralysis or severe dysfunction, only a moderately severe
      dysfunction (50%), or moderate dysfunction (50%). The forehead was the most
      affected area measured. At 3 months, all patients had recovered their normal
      facial nerve function. The overall improvement in facial nerve function was 40%
      for the patients classified initially with moderately severe dysfunction and 60%
      for those with moderate dysfunction. CONCLUSION: The frequency of facial nerve
      injury was related to the diagnosis of the temporomandibular pathology and
      surgical procedures. Facial nerve impairment was shown to be of a temporary
      nature. Moreover, there is a need to standardize the reporting of facial nerve
      recovery.

PMID- 17448851
TI  - Relationships between surgical difficulty and postoperative pain in lower third
      molar extractions.
AB  - PURPOSE: To investigate the influence of surgical difficulty on postoperative
      pain after extraction of mandibular third molars. MATERIALS AND METHODS: A
      prospective study was performed of 139 patients who underwent a total of 157
      mandibular third molar extractions. For evaluation of surgical difficulty, a 4
      class scale was completed after surgery: I, extraction with forceps only; II,
      extraction requiring osteotomy; III, extraction requiring osteotomy and coronal
      section; IV, complex extraction (root section). The duration of surgery was also
      recorded. Postoperative pain was evaluated using a visual analog scale that each
      patient completed daily until day 6 postsurgery, at which time the sutures were
      removed. RESULTS: A statistically significant relationship was observed between
      surgical difficulty (as rated on the scale) and postoperative pain. Longer
      interventions generally produced more pain. CONCLUSIONS: Pain after extraction of
      a mandibular third molar increases with increased surgical difficulty and
      duration of the intervention.

PMID- 17448852
TI  - Prevalence of postoperative complications after orthognathic surgery: a 15-year
      review.
AB  - PURPOSE: This study was conducted to determine the prevalence of postoperative
      complications after orthognathic surgery and evaluate the use of antibiotic
      prophylaxis in relation to the infection rate. PATIENTS AND METHODS: All patients
      undergoing orthognathic procedures between 1990 and 2004 were studied
      retrospectively by retrieving their individual medical records. Demographic data,
      intraoperative data (specific orthognathic procedures and duration of operation),
      and postoperative data (type and duration of antibiotic prophylaxis and presence
      of postoperative complications) were recorded. Patients noted to have suffered
      any postoperative complications were studied in detail, and various factors,
      including gender, age, duration of operation, and use of prophylactic
      antibiotics, were analyzed using statistical tests in relation to postoperative
      infection. RESULTS: A total of 2,910 orthognathic procedures were performed on
      1,294 consecutive patients in the 15-year period, with 1,070 patients undergoing
      bimaxillary procedures and 224 patients undergoing single-jaw surgery. The
      orthognathic surgery-related complication rate was 9.7%, of which 7.4% was
      related to postoperative infection. Of the cases of infection, 58.3% were acute
      infection and 41.7% were chronic infection. Patients who received a single
      preoperative dose of antibiotics had a significantly higher infection rate
      (17.3%) than those who received postoperative antibiotics for various durations.
      CONCLUSIONS: The prevalence of infection after orthognathic surgery was
      relatively low given the complexity of the procedures. No particular orthognathic
      procedure was more susceptible to infection. A preoperative dose of prophylactic
      antibiotics together with at least 2 days of postoperative doses was useful in
      reducing the infection rate compared with only a single dose of prophylactic
      antibiotics.

PMID- 17448853
TI  - Surgical induction of temporomandibular joint ankylosis: an animal model.
AB  - PURPOSE: The aim of this study was to develop an animal model of
      temporomandibular joint (TMJ) bony ankylosis for future evaluation of surgical
      reconstructive methods. MATERIALS AND METHODS: An animal model was selected on
      the basis of 2 sequential experiments. Four goats and 4 minipigs were used in the
      first experiment, in which 1 goat and 1 minipig served as control animals.
      Condylectomy with disc preservation was performed on 1 side of 3 animals in each
      group. On the contralateral TMJ, condylectomy with discectomy was performed, and
      the arthroplasty gap was filled with the autogenous bone chips. In the second
      experiment, TMJ ankylosis was induced bilaterally in 3 additional animals of the
      species that achieved better ankylosis results in the first experiment. All
      animals were killed postoperatively at 3 months, and the TMJ complexes were
      examined by plain radiography, computed tomography, and histological evaluation.
      RESULTS: In the first experiment, only fibrous ankylosis was observed in the bone
      grafted side of 2 goats and 3 minipigs, whereas fibro-osseous ankylosis was
      achieved in the remaining goat. The extent of ankylosis was found to be more
      severe in the goats than the minipigs. Hence, goats were selected for bilateral
      surgery in the second experiment, which achieved consistent bony ankylosis of the
      TMJ in all animals. CONCLUSIONS: Goats provide a better TMJ bony ankylosis model
      than minipigs. Consistent bony ankylosis can be induced by bilateral
      condylectomy, disectomy, and bone grafting of the arthroplasty gap.

PMID- 17448855
TI  - Implant treatment without bone grafting in edentulous severely resorbed maxillas:
      a long-term follow-up study.
AB  - PURPOSE: To evaluate retrospectively the surgical outcome of tilted implants in
      severely resorbed edentulous maxillas as an alternative to bone grafting and the
      prosthodontic outcome of posterior extension bridges on tilted implants. PATIENTS
      AND METHODS: A total of 33 consecutive patients with severely resorbed edentulous
      maxillas participated in the study. In these patients, the maxillary bone volumes
      were insufficient for conventional placement of implants to support a fixed
      prosthesis. As an alternative to bone transplantation, a surgical technique with
      fenestration of the maxillary sinus to visualize the total amount of maxillary
      bone was used, followed by implant placement in a tilted manner along the
      anterior maxillary sinus wall. Thus, 4 to 6 implants of optimal length could be
      installed in each patient. Nineteen patients were included in this long-term
      follow-up study and were eligible for clinical evaluation at 8 to 12 years (mean,
      10 years) after second-stage surgery. Each patient was examined clinically and
      radiographically. RESULTS: The 19 patients had a total of 103 implants. In 2 of
      these patients, 3 fixtures were lost during the first year after second-stage
      surgery. All other patients had all implants intact with functionally fixed
      dental prostheses, corresponding to a success rate of 97%. Radiographic
      examination showed bone resorption in 10% of the implants (10 implants in 5
      patients with a total number of 27 implants), with a mean bone loss of 1.2 mm.
      Mucositis was seen in 47% of the patients. CONCLUSIONS: This long-term follow-up
      study (mean time, 10 years) demonstrates that patients with a severely resorbed
      maxilla can be treated successfully with conventional implant treatment. This
      simplified surgical technique can be an alternative to the more resource
      demanding technique with bone grafting.

PMID- 17448854
TI  - Long-term results of jaw reconstruction with microsurgical fibula grafts and
      dental implants.
AB  - PURPOSE: The aim of this retrospective study was to evaluate the long-term
      utility of the free fibula flap for the reconstruction of the maxilla and
      mandible and to investigate its suitability for prosthetic rehabilitation with
      dental implants focusing on implant survival and implant-related morbidity.
      MATERIALS AND METHODS: Thirty patients who underwent microsurgical reconstruction
      of the upper or lower jaw after resection from 1992 to 1994 and were available
      for follow-up examination were included in the investigation. The primary
      afflictions were malignant tumors, alveolar atrophy, or osteomyelitis. Clinical
      and radiologic findings were gathered and evaluated with emphasis on the
      radiologic follow-up as well as clinical investigations disclosing implant
      related complications. RESULTS: The fibula proved very suitable for the
      reconstruction of the upper and lower jaw, allowing rehabilitation with dental
      implants in all cases. Additionally, the peri-implant bone resorption and the
      overall complication rate proved to be low. In 93 of 128 implants, probing depths
      ranged from 2 to 3 mm. In 20 implants, probing depths of 4 to 6 mm were observed.
      In 4 implants, probing depths of greater than 7 mm were observed. These values
      corresponded with the radiologically assessed values. CONCLUSION: The
      reconstruction of the upper and lower jaw with a microsurgically reanastomosed
      fibula flap, in combination with dental implants, leads to satisfactory
      functional and esthetic results. The fibula flap seems resistant to peri
      implantary resorption processes and is capable of withstanding the masticatory
      forces that develop during functional loading. In conjunction with the new
      prosthetic attachments, like the titanium magnetic inserts, the fixation of cover
      dentures and the oral hygiene is simplified and improved.

PMID- 17448856
TI  - An unusual response associated with cross-linked porcine dermal collagen
      (ENDURAGen) used for reconstruction of a post-traumatic lateral nasal wall
      deformity.

PMID- 17448857
TI  - Superior repositioning of the maxilla in thalassemia-induced facial deformity:
      report of 3 cases and a review of the literature.

PMID- 17448858
TI  - Neck abscess and necrotizing fasciitis caused by Salmonella infection: a report
      of 2 cases.

PMID- 17448859
TI  - Ultrasound piezoelectric vibrations to perform osteotomies in rhinoplasty.

PMID- 17448860
TI  - Endoscope-assisted repair of medial orbital wall fractures using a
      retrocaruncular approach.

PMID- 17448861
TI  - Anterior maxillary distraction by tooth-borne palatal distractor.

PMID- 17448862
TI  - Vertical alveolar bone distraction with polytetrafloroethylene membrane for
      implant application: a technical note.

PMID- 17448863
TI  - Le Fort maxillary swing procedure for posterior maxilla tumor extirpation.

PMID- 17448864
TI  - Intensity-modulated radiotherapy for early larynx cancer: is there a role?

PMID- 17448865
TI  - Learning physics in radiation oncology.

PMID- 17448866
TI  - American Board of Radiology Maintenance of Certification - Part IV: practice
      quality improvement for radiation oncology.
AB  - Maintenance of Certification is a physician-based response to public concerns
      about the quality of medical care and physician competency in a rapidly evolving,
      technically demanding specialty. The American Board of Radiology (ABR) has
      previously described the first three components of the Maintenance of
      Certification. The ABR is currently developing a program in practice performance,
      completing Part IV of the competencies. The Practice Quality Improvement (PQI)
      program is meant to critically evaluate meaningful aspects of a physician's
      practice in a simple manner, using identifiable metrics and self-assessment to
      include an action plan for quality improvement. Each diplomate will be expected
      to complete three PQI projects during a full 10-year Maintenance of Certification
      cycle. Current diplomates with time-limited certificates will find prorated
      requirements determined by their year of certification on the ABR Website.
      Diplomates will have the option of completing zero to two Type I PQI projects
      (assessing factors relevant to clinical practice by peer review and self
      reporting) and one to three Type II projects (i.e., at least one Type II projects
      of the three required, assessing parameters of practice by comparison with
      evidence-based guidelines, consensus statements, or peer comparisons; Type II
      projects are initiated and managed by professional societies). Several examples
      of Type I projects that might be offered by societies or directly through the ABR
      are provided, as well as highlights of the two Type II projects that have sought
      ABR qualification: the American Society for Therapeutic Radiology and Oncology's
      Performance Assessment for the Advancement of Radiation Oncology Treatment
      program and American College of Radiology's RO-PEER program. An additional
      objective of the PQI is to develop national databases for future reference using
      aggregate data from the PQI projects.

PMID- 17448867
TI  - Recommendations for radioembolization of hepatic malignancies using yttrium-90
      microsphere brachytherapy: a consensus panel report from the radioembolization
      brachytherapy oncology consortium.
AB  - PURPOSE: To standardize the indications, techniques, multimodality treatment
      approaches, and dosimetry to be used for yttrium-90 (Y90) microsphere hepatic
      brachytherapy. METHODS AND MATERIALS: Members of the Radioembolization
      Brachytherapy Oncology Consortium met as an independent group of experts in
      interventional radiology, radiation oncology, nuclear medicine, medical oncology,
      and surgical oncology to identify areas of consensus and controversy and to issue
      clinical guidelines for Y90 microsphere brachytherapy. RESULTS: A total of 14
      recommendations are made with category 2A consensus. Key findings include the
      following. Sufficient evidence exists to support the safety and effectiveness of
      Y90 microsphere therapy. A meticulous angiographic technique is required to
      prevent complications. Resin microsphere prescribed activity is best estimated by
      the body surface area method. By virtue of their training, certification, and
      contribution to Y90 microsphere treatment programs, the disciplines of radiation
      oncology, nuclear medicine, and interventional radiology are all qualified to use
      Y90 microspheres. The panel strongly advocates the creation of a treatment
      registry with uniform reporting criteria. Initiation of clinical trials is
      essential to further define the safety and role of Y90 microspheres in the
      context of currently available therapies. CONCLUSIONS: Yttrium-90 microsphere
      therapy is a complex procedure that requires multidisciplinary management for
      safety and success. Practitioners and cooperative groups are encouraged to use
      these guidelines to formulate their treatment and dose-reporting policies.

PMID- 17448868
TI  - Use of individual fraction size data from 3756 patients to directly determine the
      alpha/beta ratio of prostate cancer.
AB  - PURPOSE: To examine the effect of fraction size and total dose of radiation on
      recurrence of localized prostate cancer. METHODS AND MATERIALS: A total of 3756
      patients treated with radiation monotherapy at three institutions were analyzed,
      including 185 high-dose-rate brachytherapy (HDRB) boost patients. The 5th to 95th
      centiles of external beam radiotherapy (EBRT) fraction sizes and doses were 1.8
      to 2.86 Gy, and 57.4 to 77.4 Gy, respectively, and HDRB fractional doses were
      between 5.5 and 12 Gy, totaling 147 unique fractionation schedules. Failure was
      defined by one biochemical (nadir + 2 ng/ml) and two advanced disease endpoints.
      The alpha/beta ratios were estimated via a proportional hazards model stratified
      by risk severity and institution. RESULTS: The alpha/beta ratio using biochemical
      recurrence was 3.7 Gy (95% confidence interval [95% CI], 1.1, infinity Gy) for
      EBRT-only cases and 2.6 Gy (95% CI, 0.9, 4.8 Gy) after the addition of HDRB data.
      This estimate was highly dependent on an HDRB homogeneity correction factor (120%
      HDRB dose increase; alpha/beta ratio 4.5 Gy, 95% CI 1.6, 8.7 Gy). A 5-Gy increase
      in total dose reduced the hazard of failure by 16% (95% CI 11, 21%, p < 0.0001),
      and had more impact as follow-up matured (p < 0.0003). The clinically advanced
      endpoints concurred with the biochemical failure results, albeit with less
      precision. CONCLUSIONS: This study supports the concept that the alpha/beta ratio
      of prostate cancer is low, although considerable uncertainty remains in the
      estimated value. Outcome data from EBRT studies using substantially higher doses
      per fraction are needed to show increased precision in these estimates.

PMID- 17448869
TI  - Does concurrent radiochemotherapy affect cosmetic results in the adjuvant setting
      after breast-conserving surgery? Results of the ARCOSEIN multicenter, Phase III
      study: patients' and doctors' views.
AB  - PURPOSE: To evaluate the cosmetic results of sequential vs. concurrent adjuvant
      chemotherapy with radiotherapy after breast-conserving surgery for breast cancer,
      and to compare ratings by patients and physicians. METHODS AND MATERIALS: From
      1996 to 2000, 716 patients with Stage I-II breast cancers were included in a
      multicenter, Phase III trial (the ARCOSEIN study) comparing, after breast
      conserving surgery with axillary dissection, sequential treatment with
      chemotherapy first followed by radiotherapy vs. chemotherapy administered
      concurrently with radiotherapy. Cosmetic results with regard to both the overall
      aspect of the breast and specific changes (color, scar) were evaluated in a total
      of 214 patients (107 in each arm) by means of questionnaires to both the patient
      and a physician whose rating was blinded to treatment allocation. RESULTS:
      Patients' overall satisfaction with cosmesis was not statistically different
      between the two arms, with approximately 92% with at least satisfactory results
      (p = 0.72), although differences between the treated and untreated breasts were
      greater after the concurrent regimen (29% vs. 14% with more than moderate
      differences; p = 0.0015). Physician assessment of overall cosmesis was less
      favorable, with lower rates of at least satisfactory results in the concurrent
      arm (60% vs. 85%; p = 0.001). Consequently, the concordance for overall
      satisfaction with cosmesis between patients and doctors was only fair (kappa =
      0.62). CONCLUSION: After breast-conserving surgery, the concurrent use of
      chemotherapy with radiotherapy is significantly associated with greater
      differences between the breasts. These differences do not translate into
      patients' lessened satisfaction with cosmesis.

PMID- 17448870
TI  - Multicenter validation of recursive partitioning analysis classification for
      patients with squamous cell head and neck carcinoma treated with surgery and
      postoperative radiotherapy.
AB  - PURPOSE: To validate the recursive partitioning analysis (RPA) classification
      system for squamous cell head and neck cancer as recently reported by the VU
      University Medical Center. METHODS AND MATERIALS: In eight Dutch head and neck
      cancer centers, data necessary to classify patients according to the RPA system
      were retrospectively collected from the charts of a group of 780 patients treated
      between 1989 and 2003. The patients in this validation group were classified
      according to the RPA classification system. For each endpoint, the 5-year values
      and hazard ratios were calculated and compared with the results of the VU
      University Medical Center. The RPA classification system was considered valid if
      the hazard ratio of the validation population was within the 95% confidence
      interval of the VU University Medical Center study population. RESULTS: The
      locoregional control rate was 82%, 75%, and 63% at 5 years for those with class
      I, II, and III, respectively (p < 0.0001). The hazard ratio for the locoregional
      control rate relative to class I was 1.44 (95% confidence interval, 0.97-2.16)
      for class II and 2.37 (95% confidence interval, 1.57-3.57) for class III. Similar
      results were found for the distant metastasis, overall survival, and disease-free
      survival rates. CONCLUSION: The RPA classification system for head and neck
      squamous cell carcinoma in the postoperative setting, which was originally
      designed at one center, proved to be valid in a multicenter setting among
      patients included in a national multicenter study. This validated RPA
      classification scheme can be used to assess standard treatment strategies for
      head and neck squamous cell carcinoma in the postoperative setting, as well as in
      the design of future prospective studies.

PMID- 17448871
TI  - Positron emission tomography-guided, focal-dose escalation using intensity
      modulated radiotherapy for head and neck cancer.
AB  - PURPOSE: To assess the feasibility of intensity-modulated radiotherapy (IMRT)
      using positron emission tomography (PET)-guided dose escalation, and to determine
      the maximum tolerated dose in head and neck cancer. METHODS AND MATERIALS: A
      Phase I clinical trial was designed to escalate the dose limited to the [(18)
      F]fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)
      delineated subvolume within the gross tumor volume. Positron emission tomography
      scanning was performed in the treatment position. Intensity-modulated
      radiotherapy with an upfront simultaneously integrated boost was employed. Two
      dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10
      fractions. Standard IMRT was applied for the remaining 22 fractions of 2.16 Gy.
      RESULTS: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level
      I, and 18 at dose level II; 39 patients completed the planned therapy. The median
      follow-up for surviving patients was 14 months. Two cases of dose-limiting
      toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One
      treatment-related death at dose level II halted the study. Complete response was
      observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I
      and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and
      87% (p = n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose
      levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the
      boosted (18)F-FDG-PET-delineated region. CONCLUSIONS: For head and neck cancer,
      PET-guided dose escalation appears to be well-tolerated. The maximum tolerated
      dose was not reached at the investigated dose levels.

PMID- 17448872
TI  - Inhibition of transforming growth factor-beta signaling in normal lung epithelial
      cells confers resistance to ionizing radiation.
AB  - PURPOSE: To address the functional role of radiation-induced transforming growth
      factor-beta (TGF-beta) signaling in a normal epithelial background, we selected a
      spontaneously immortalized lung epithelial cell line derived from the normal lung
      tissue of a dominant-negative mutant of the TGF-beta RII (DeltaRII) transgenic
      mouse that conditionally expressed DeltaRII under the control of the
      metallothionein promoter (MT-1), and assessed this cell line's response to
      radiation. METHODS AND MATERIALS: A spontaneously immortalized lung epithelial
      cell culture (SILECC) was established and all analyses were performed within 50
      passages. Colony-forming and terminal transferase dUPT nick end labeling (TUNEL)
      assays were used to assess clonogenic inhibition and apoptosis, respectively.
      Western-blot analysis was performed to assess the kinetics of p21, bax, and RII
      proteins. Transforming growth factor-beta-responsive promoter activity was
      measured using dual-luciferase reporter assay. RESULTS: Exposure to ZnSO(4)
      inhibited TGF-beta signaling induced either by recombinant TGF-beta1 or ionizing
      radiation. The SILECC, treated with either ZnSO(4) or neutralizing antibody
      against TGF-beta, showed a significant increase in radio-resistance compared to
      untreated cells. Furthermore, the expression of DeltaRII inhibited the radiation
      induced up-regulation of the TGF-beta effector gene p21(waf1/cip1). CONCLUSIONS:
      Our findings imply that inhibition of radiation-induced TGF-beta signaling via
      abrogation of the RII function enhances the radio-resistance of normal lung
      epithelial cells, and this can be directly attributed to the loss of TGF-beta
      signaling function.

PMID- 17448874
TI  - No significant endothelial apoptosis in the radiation-induced gastrointestinal
      syndrome.
AB  - PURPOSE: This report addresses the incidence of vascular endothelial cell
      apoptosis in the mouse small intestine in relation to the radiation-induced
      gastrointestinal (GI) syndrome. METHODS AND MATERIALS: Nonanesthetized mice
      received whole-body irradiation at doses above and below the threshold for death
      from the GI syndrome with 250 kVp X-rays, (137)Cs gamma rays, epithermal neutrons
      alone, or a unique approach for selective vascular irradiation using epithermal
      neutrons in combination with boronated liposomes that are restricted to the
      blood. Both terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling
      (TUNEL) staining for apoptosis and dual-fluorescence staining for apoptosis and
      endothelial cells were carried out in jejunal cross-sections at 4 h
      postirradiation. RESULTS: Most apoptotic cells were in the crypt epithelium. The
      number of TUNEL-positive nuclei per villus was low (1.62 +/- 0.03, mean +/- SEM)
      for all irradiation modalities and showed no dose-response as a function of blood
      vessel dose, even as the dose crossed the threshold for death from the GI
      syndrome. Dual-fluorescence staining for apoptosis and endothelial cells verified
      the TUNEL results and identified the apoptotic nuclei in the villi as CD45
      positive leukocytes. CONCLUSION: These data do not support the hypothesis that
      vascular endothelial cell apoptosis is the cause of the GI syndrome.

PMID- 17448873
TI  - Temporal onset of hypoxia and oxidative stress after pulmonary irradiation.
AB  - PURPOSE: To investigate the temporal onset of hypoxia following irradiation, and
      to show how it relates to pulmonary vascular damage, macrophage accumulation, and
      the production of reactive oxygen species and cytokines. Our previous studies
      showed that tissue hypoxia in the lung after irradiation contributed to radiation
      induced injury. METHODS AND MATERIALS: Female Fisher 344 rats were irradiated to
      the right hemithorax with a single dose of 28 Gy. Serial studies were performed
      up to 20 weeks following irradiation. Radionuclide lung-perfusion studies were
      performed to detect changes in pulmonary vasculature. Immunohistochemical studies
      were conducted to study macrophages, tissue hypoxia (carbonic anhydrase-9
      marker), oxidative stress (8-hydroxy-2'-deoxyguanosine), and the expression of
      profibrogenic (transforming growth factor-beta [TGF-beta]) and proangiogenic
      (vascular endothelial growth factor [VEGF]) cytokines. RESULTS: Significant
      changes in lung perfusion along with tissue hypoxia were observed 3 days after
      irradiation. Significant oxidative stress was detected 1 week after radiation,
      whereas macrophages started to accumulate at 4 weeks. A significant increase in
      TGF-beta expression was seen within 1 day after radiation, and for VEGF at 2
      weeks after radiation. Levels of hypoxia, oxidative stress, and both cytokines
      continued to rise with time after irradiation. The steepest increase correlated
      with vast macrophage accumulation. CONCLUSIONS: Early changes in lung perfusion,
      among other factors initiate, the development of hypoxia and chronic oxidative
      stress after irradiation. Tissue hypoxia is associated with a significant
      increase in the activation of macrophages and their continuous production of
      reactive oxygen species, stimulating the production of fibrogenic and angiogenic
      cytokines, and maintaining the development of chronic radiation-induced lung
      injury.

PMID- 17448875
TI  - Characterizing the tumor response to treatment with combretastatin A4 phosphate.
AB  - PURPOSE: To examine the pathophysiologic impact of treatment with combretastatin
      A4 phosphate (CA4P) in regions of tumors that ultimately either necrose or
      survive treatment with this agent. METHODS AND MATERIALS: Proliferation,
      perfusion, vessel density, and expression of vascular endothelial growth factor
      (VEGF) were analyzed in the KHT tumor model after treatment with CA4P. Analyses
      were conducted in the whole tumor and the tumor periphery. RESULTS: Perfusion in
      the tumor periphery decreased 4 h after treatment, but returned to baseline 20 h
      later. Whole-tumor perfusion also decreased 4 h after treatment, but did not
      return to baseline. Vessel density decreased in the tumor as a whole, but not in
      the tumor periphery. No significant effect on the expression of VEGF was
      observed, but a decrease in proliferation in the whole tumor and the periphery
      was noted. CONCLUSIONS: The present study shows that those areas of a tumor that
      survive treatment with CA4P are affected by CA4P exposure, though only
      transiently. The decrease in perfusion could negatively affect therapies
      utilizing the combination of CA4P and conventional anticancer agents by
      decreasing drug delivery and tissue oxygenation. These findings suggest that the
      timing of CA4P treatments when used in conjunction with conventional anticancer
      therapies should be considered carefully.

PMID- 17448876
TI  - Treatment combining X-irradiation and a ribonucleoside anticancer drug, TAS106,
      effectively suppresses the growth of tumor cells transplanted in mice.
AB  - PURPOSE: To examine the in vivo antitumor efficacy of X-irradiation combined with
      administration of a ribonucleoside anticancer drug, 1-(3-C-ethynyl-beta-D-ribo
      pentofuranosyl)cytosine (TAS106, ECyd), to tumor cell-transplanted mice. METHODS
      AND MATERIALS: Colon26 murine rectum adenocarcinoma cells and MKN45 human gastric
      adenocarcinoma cells were inoculated into the footpad in BALB/c mice and severe
      combined immunodeficient mice, respectively. They were treated with a relatively
      low dose of X-irradiation (2 Gy) and low amounts of TAS106 (0.1 mg/kg and 0.5
      mg/kg). The tumor growth was monitored by measuring the tumor volume from Day 5
      to Day 16 for Colon26 and from Day 7 to Day 20 for MKN45. Histologic analyses for
      proliferative and apoptotic cells in the tumors were performed using Ki-67
      immunohistochemical and terminal deoxynucleotidyl transferase-mediated nick end
      labeling staining. The expression of survivin, a key molecule related to tumor
      survival, was assessed by quantitative polymerase chain reaction and
      immunohistochemical analysis. RESULTS: When X-irradiation and TAS106 treatment
      were combined, significant inhibition of tumor growth was observed in both types
      of tumors compared with mice treated with X-irradiation or TAS106 alone. Marked
      inhibition of tumor growth was observed in half of the mice that received the
      combined treatment three times at 2-day intervals. Parallel to these phenomena,
      the suppression of survivin expression and appearance of Ki-67-negative and
      apoptotic cells were observed. CONCLUSIONS: X-irradiation and TAS106 effectively
      suppress tumor growth in mice. The inhibition of survivin expression by TAS106 is
      thought to mainly contribute to the suppression of the tumor growth.

PMID- 17448877
TI  - Radiobiologic modeling of cytoprotection effects in radiotherapy.
AB  - PURPOSE: To investigate the potential for mathematical modeling of the normal
      tissue-sparing effects of cytoprotective agents used in conjunction with
      radiotherapy and chemotherapy. METHODS AND MATERIALS: The linear quadratic model
      was modified to include a "cytoprotection factor," in two alternative ways. The
      published results on the incidence of treatment-related oral mucositis in
      patients treated for head-and-neck carcinoma using radiotherapy alone or combined
      with chemotherapy were assessed against the model to determine the likely values
      of the cytoprotection factor required to confer a reasonable degree of
      cytoprotection. RESULTS: In both of the model alternatives considered, a
      cytoprotection factor value of < or = 0.85 was required for a clinically
      detectable degree of cytoprotection to be realized. A cytoprotection factor value
      of 0.85 would mean that the radiation sensitivity coefficients would be
      effectively reduced by 15% on account of the action of the cytoprotector.
      CONCLUSION: The incorporation of a cytoprotection factor into an existing linear
      quadratic method would allow a quantitative assessment of cytoprotection and
      could be useful in the design of future clinical studies.

PMID- 17448878
TI  - Respiratory motion of the heart and positional reproducibility under active
      breathing control.
AB  - PURPOSE: To reduce cardiotoxicity from breast radiotherapy (RT), innovative
      techniques are under investigation. Information about cardiac motion with
      respiration and positional reproducibility under active breathing control (ABC)
      is necessary to evaluate these techniques. METHODS AND MATERIALS: Patients
      requiring loco-regional RT for breast cancer were scanned by computed tomography
      using an ABC device at various breath-hold states, before and during treatment.
      Ten patients were studied. For each patient, 12 datasets were analyzed. Mutual
      information-based regional rigid alignment was used to determine the magnitude
      and reproducibility of cardiac motion as a function of breathing state. For each
      scan session, motion was quantified by evaluating the displacement of a point
      along the left anterior descending artery (LAD) with respect to its position at
      end expiration. Long-term positional reproducibility was also assessed. RESULTS:
      Displacement of the LAD was greatest in the inferior direction, moderate in the
      anterior direction, and lowest in the left-right direction. At shallow breathing
      states, the average displacement of LAD position was up to 6 mm in the inferior
      direction. The maximum displacement in any patient was 2.8 cm in the inferior
      direction, between expiration and deep-inspiration breath hold. At end
      expiration, the long-term reproducibility (SD) of the LAD position was 3 mm in
      the A-P, 6 mm in the S-I, and 4 mm in the L-R directions. At deep-inspiration
      breath hold, long-term reproducibility was 3 mm in the A-P, 7 mm in the S-I, and
      3 mm in the L-R directions. CONCLUSIONS: These data demonstrate the extent of LAD
      displacement that occurs with shallow breathing and with deep-inspiration breath
      hold. This information may guide optimization studies considering the effects of
      respiratory motion and reproducibility of cardiac position on cardiac dose, both
      with and without ABC.

PMID- 17448879
TI  - Reproducibility of the abdominal and chest wall position by voluntary breath-hold
      technique using a laser-based monitoring and visual feedback system.
AB  - PURPOSE: The voluntary breath-hold (BH) technique is a simple method to control
      the respiration-related motion of a tumor during irradiation. However, the
      abdominal and chest wall position may not be accurately reproduced using the BH
      technique. The purpose of this study was to examine whether visual feedback can
      reduce the fluctuation in wall motion during BH using a new respiratory
      monitoring device. METHODS AND MATERIALS: We developed a laser-based BH
      monitoring and visual feedback system. For this study, five healthy volunteers
      were enrolled. The volunteers, practicing abdominal breathing, performed shallow
      end-expiration BH (SEBH), shallow end-inspiration BH (SIBH), and deep end
      inspiration BH (DIBH) with or without visual feedback. The abdominal and chest
      wall positions were measured at 80-ms intervals during BHs. RESULTS: The
      fluctuation in the chest wall position was smaller than that of the abdominal
      wall position. The reproducibility of the wall position was improved by visual
      feedback. With a monitoring device, visual feedback reduced the mean deviation of
      the abdominal wall from 2.1 +/- 1.3 mm to 1.5 +/- 0.5 mm, 2.5 +/- 1.9 mm to 1.1
      +/- 0.4 mm, and 6.6 +/- 2.4 mm to 2.6 +/- 1.4 mm in SEBH, SIBH, and DIBH,
      respectively. CONCLUSIONS: Volunteers can perform the BH maneuver in a highly
      reproducible fashion when informed about the position of the wall, although in
      the case of DIBH, the deviation in the wall position remained substantial.

PMID- 17448880
TI  - Feasibility of image registration and intensity-modulated radiotherapy planning
      with hyperpolarized helium-3 magnetic resonance imaging for non-small-cell lung
      cancer.
AB  - PURPOSE: To demonstrate the feasibility of registering hyperpolarized helium-3
      magnetic resonance images ((3)He-MRI) to X-ray computed tomography (CT) for
      functionally weighted intensity-modulated radiotherapy (IMRT) planning. METHODS
      AND MATERIALS: Six patients with non-small-cell lung cancer underwent (3)He
      ventilation MRI, which was fused with radiotherapy planning CT using rigid
      registration. Registration accuracy was assessed using an overlap coefficient,
      calculated as the proportion of the segmented (3)He-MR volume (V(MRI)) that
      intersects the segmented CT lung volume expressed as a percentage of V(MRI). For
      each patient, an IMRT plan that minimized the volume of total lung receiving a
      dose > or = 20 Gy (V(20)) was compared with a plan that minimized the V(20) to
      well-ventilated lung defined by the registered (3)He-MRI. RESULTS: The (3)He-MRI
      and CT were registered with sufficient accuracy to enable functionally guided
      IMRT planning (median overlap, 89%; range, 72-97%). In comparison with the total
      lung IMRT plans, IMRT constrained with (3)He-MRI reduced the V(20) not only for
      the well-ventilated lung (median reduction, 3.1%; range, 0.4-5.1%; p = 0.028) but
      also for the total lung volume (median reduction, 1.6%; range, 0.2-3.7%; p =
      0.028). CONCLUSIONS: Statistically significant improvements to IMRT plans are
      possible using functional information provided by (3)He-MRI that has been
      registered to radiotherapy planning CT.

PMID- 17448881
TI  - Target coverage in image-guided stereotactic body radiotherapy of liver tumors.
AB  - PURPOSE: To determine the effect of image-guided procedures (with computed
      tomography [CT] and electronic portal images before each treatment fraction) on
      target coverage in stereotactic body radiotherapy for liver patients using a
      stereotactic body frame (SBF) and abdominal compression. CT guidance was used to
      correct for day-to-day variations in the tumor's mean position in the SBF.
      METHODS AND MATERIALS: By retrospectively evaluating 57 treatment sessions, tumor
      coverage, as obtained with the clinically applied CT-guided protocol, was
      compared with that of alternative procedures. The internal target volume-plus
      (ITV(+)) was introduced to explicitly include uncertainties in tumor delineations
      resulting from CT-imaging artifacts caused by residual respiratory motion. Tumor
      coverage was defined as the volume overlap of the ITV(+), derived from a tumor
      delineated in a treatment CT scan, and the planning target volume. Patient
      stability in the SBF, after acquisition of the treatment CT scan, was evaluated
      by measuring the displacement of the bony anatomy in the electronic portal images
      relative to CT. RESULTS: Application of our clinical protocol (with setup
      corrections following from manual measurements of the distances between the
      contours of the planning target volume and the daily clinical target volume in
      three orthogonal planes, multiple two-dimensional) increased the frequency of
      nearly full (> or = 99%) ITV(+) coverage to 77% compared with 63% without setup
      correction. An automated three-dimensional method further improved the frequency
      to 96%. Patient displacements in the SBF were generally small (< or = 2 mm, 1
      standard deviation), but large craniocaudal displacements (maximal 7.2 mm) were
      occasionally observed. CONCLUSION: Daily, CT-assisted patient setup may
      substantially improve tumor coverage, especially with the automated three
      dimensional procedure. In the present treatment design, patient stability in the
      SBF should be verified with portal imaging.

PMID- 17448882
TI  - Hypoxia dose painting by numbers: a planning study.
AB  - PURPOSE: To investigate the feasibility of different hypoxia dose painting
      strategies in head-and-neck radiotherapy; the potential benefit was limited by
      the stipulation of isotoxicity with respect to the conventional intensity
      modulated radiotherapy (IMRT) treatment. METHODS AND MATERIALS: Thirteen head-and
      neck cancer patients were included into the planning study. For each patient,
      three different treatment plans were created: a conventional IMRT plan, an
      additional uniform dose escalation (uniDE) of 10% to the fluorodeoxyglucose (FDG)
      positive volume, and a plan in which dose painting by numbers (DPBN) was
      implemented. Dose painting by numbers was realized according to a map of dose
      escalation factors calculated from dynamic [(18)F]-fluoromisonidazole (FMISO)
      positron emission tomography data. RESULTS: Both dose-escalation approaches were
      shown to be feasible under the constraint of limiting normal tissue doses to the
      level of conventional IMRT. For DPBN, the prescriptions could be fulfilled in
      larger regions of the target than for uniDE. Fluorodeoxyglucose-positive volumes
      had sizes up to 94 cm(3). In contrast, regions receiving comparable dose levels
      with DPBN presented volumes in the range of 0-2.7 cm(3). Overtreatment of the
      target was observed with uniDE in most of the cases, whereas some regions did not
      receive the required dose to overcome hypoxia-induced radiation insensitivity.
      Tumor control probability increased from 55.9% with conventional IMRT to 57.7%
      for the uniDE method in the patient group. For DPBN, a potential increase in
      tumor control probability from 55.9% to 70.2% was determined. Therefore, DPBN
      seems to result in higher benefits for the patients. CONCLUSION: Dose painting by
      numbers delivers the dose more effectively than an additional uniform boost to
      the FDG-positive area. If hypoxia could be adequately quantified with a simple
      imaging technique like FMISO positron emission tomography, DPBN in head-and-neck
      cancer could substantially increase tumor control.

PMID- 17448883
TI  - Uncertainty estimation in intensity-modulated radiotherapy absolute dosimetry
      verification.
AB  - PURPOSE: Intensity-modulated radiotherapy (IMRT) represents an important method
      for improving RT. The IMRT relative dosimetry checks are well established;
      however, open questions remain in reference dosimetry with ionization chambers
      (ICs). The main problem is the departure of the measurement conditions from the
      reference ones; thus, additional uncertainty is introduced into the dose
      determination. The goal of this study was to assess this effect systematically.
      METHODS AND MATERIALS: Monte Carlo calculations and dosimetric measurements with
      five different detectors were performed for a number of representative IMRT
      cases, covering both step-and-shoot and dynamic delivery. RESULTS: Using ICs with
      volumes of about 0.125 cm(3) or less, good agreement was observed among the
      detectors in most of the situations studied. These results also agreed well with
      the Monte Carlo-calculated nonreference correction factors (c factors).
      Additionally, we found a general correlation between the IC position relative to
      a segment and the derived correction factor c, which can be used to estimate the
      expected overall uncertainty of the treatment. CONCLUSION: The increase of the
      reference dose relative standard uncertainty measured with ICs introduced by
      nonreference conditions when verifying an entire IMRT plan is about 1-1.5%,
      provided that appropriate small-volume chambers are used. The overall standard
      uncertainty of the measured IMRT dose amounts to about 2.3%, including the 0.5%
      of reproducibility and 1.5% of uncertainty associated with the beam calibration
      factor. Solid state detectors and large-volume chambers are not well suited to
      IMRT verification dosimetry because of the greater uncertainties. An action level
      of 5% is appropriate for IMRT verification. Greater discrepancies should lead to
      a review of the dosimetric procedure, including visual inspection of treatment
      segments and energy fluence.

PMID- 17448884
TI  - Clinical target volume for rectal cancer: in regard to Roels et al. (Int J Radiat
      Oncol Biol Phys 2006;65:1129-1142).

PMID- 17448885
TI  - In regards to Dr. Garden et al. (Int J Radiat Oncol Biol Phys 2007;67:438-444).

PMID- 17448887
TI  - Be careful in getting cost-effectiveness conclusions from a debatable trial!

PMID- 17448888
TI  - Addendum to: Basic immunology of antibody targeted radiotherapy: in regard to
      Wong (Int J Radiat Oncol Biol Phys 2006;66: S8-S14).

PMID- 17448889
TI  - In regards to Allen et al. (Int J Radiat Oncol Biol Phys 2006;65:640-645).

PMID- 17448892
TI  - The effects of superoxide dismutase on H2O2 formation.
AB  - Numerous reports of the effects of overproduction of SODs have been explained on
      the basis of increased H2O2 production by the catalyzed dismutation of O2-. In
      this review we consider the effects of increasing [SOD] on H2O2 formation and
      question this explanation.

PMID- 17448893
TI  - Mitochondrial alterations in livers of Sod1-/- mice fed alcohol.
AB  - Chronic alcohol consumption induced liver injury in Cu,Zn-superoxide dismutase
      deficient mice (Sod1-/-), with extensive centrilobular necrosis and inflammation
      and a reduction in hepatic ATP content. Mechanisms by which ethanol decreased ATP
      in these mice remain unclear. We investigated alterations in mitochondria of Sod1
      /- mice produced by chronic ethanol treatment. These mitochondria had an increase
      in State 4 oxygen consumption with succinate and especially with glutamate plus
      malate compared to mitochondria from pair-fed Sod1-/- mice or mitochondria from
      wild-type mice fed dextrose or ethanol. This uncoupling was associated with a
      decrease in ADP/O and respiratory control ratios, a decline in mitochondrial
      membrane potential, enhanced mitochondrial permeability transition, and decreased
      aconitase activity. Total thiols and uncoupling protein 2 levels were elevated in
      the pair-fed Sod1-/- mitochondria, perhaps an adaptive response to oxidant
      stress. However, no such increases were found with the ethanol-fed Sod1-/-
      mitochondria, suggesting a failure to develop these adaptations. The mitochondria
      from the ethanol-fed Sod1-/- mice had elevated levels of cleaved Bax, Bak, Bcl
      xl, and adenine nucleotide translocator. Immunoprecipitation studies revealed
      increased association of Bax and Bak with the adenine nucleotide translocator.
      ADP-ATP exchange was very low in the ethanol-fed Sod1-/- mitochondria. These
      results suggest that ethanol treatment of Sod1-/- mice produces uncoupling and a
      decline in Deltapsi, swelling, increased association of proapoptotic proteins
      involved in the permeability transition, and decreased adenine nucleotide
      translocator activity, which may be responsible for the decline in ATP levels and
      development of necrosis in this model of alcohol-induced liver injury.

PMID- 17448894
TI  - Effect of zinc on the lipid peroxidation and the antioxidant defense systems of
      the alloxan-induced diabetic rabbits.
AB  - The effects of oral zinc supplementation on lipid peroxidation and the
      antioxidant defense system of alloxan (80-90 mg/kg)-induced diabetic rabbits were
      examined. Forty-five New Zealand male rabbits, 1 year old, weighing approximately
      2.5 kg, were allocated randomly and equally as control, diabetic, and zinc
      supplemented diabetic groups. After diabetes was induced, zinc-supplemented
      diabetic rabbits had 150 mg/L of zinc as zinc sulfate (ZnSO(4)) in their drinking
      tap water for 3 months. The feed and water consumption was higher in diabetic
      groups than (P<0.01) healthy rabbits. The body weight was lower in diabetic
      rabbits compared to control. The blood glucose levels were higher in diabetic
      groups than controls. The elevated plasma malondialdehyde (MDA) levels were
      determined in the diabetic group (P<0.01). The glutathione peroxidase (GSH-Px),
      catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and ceruloplasmin
      levels in the diabetic group were decreased by the effect of diabetes but there
      was no difference between zinc-supplemented diabetic and control rabbits. Serum
      zinc concentrations were lower in diabetic rabbits but iron (Fe) and copper (Cu)
      levels in sera were not different among the groups. As a result, it was concluded
      that daily zinc supplementation could reduce the harmful effects of oxidative
      stress in diabetics.

PMID- 17448895
TI  - VEGFR1 (Flt-1+/-) gene knockout leads to the disruption of VEGF-mediated
      signaling through the nitric oxide/heme oxygenase pathway in ischemic
      preconditioned myocardium.
AB  - This report demonstrates that mice deficient in Flt-1 failed to establish
      ischemic preconditioning (PC)-mediated cardioprotection in isolated working
      buffer-perfused ischemic/reperfused (I/R) hearts compared to wild type (WT)
      subjected to the same PC protocol. WT and Flt-1+/- mice were divided into four
      groups: (1) WT I/R, (2) WT + PC, (3) Flt-1+/- I/R, and (4) Flt-1+/- + PC. Group 1
      and 3 mice were subjected to 30 min of ischemia followed by 2 h of reperfusion
      and group 2 and 4 mice were subjected to four episodes of 4-min global ischemia
      followed by 6 min of reperfusion before ischemia/reperfusion. For both wild-type
      and Flt-1+/- mice, the postischemic functional recovery for the hearts was lower
      than the baseline, but the recovery for the knockout mice was less compared to
      the WT mice even in preconditioning. The myocardial infarction and apoptosis were
      higher in Flt-1+/- compared to wild-type I/R. Flt-1+/- KO mice demonstrated
      pronounced inhibition of the expression of iNOS, p-AKT & p-eNOS. Significant
      inhibition of STAT3 & CREB were also observed along with the inhibition of HO-1
      mRNA. Results demonstrate that Flt-1+/- mouse hearts are more susceptible to
      ischemia/reperfusion injury and also document that preconditioning is not as
      effective as found in WT and therefore suggest the importance of VEGF/Flt-1
      signaling in ischemic/reperfused myocardium.

PMID- 17448896
TI  - Thioredoxin-linked metabolism in Entamoeba histolytica.
AB  - Entamoeba histolytica, an intestinal protozoan that is the causative agent of
      amoebiasis, is exposed to elevated amounts of highly toxic reactive oxygen
      species during tissue invasion. In this work, we report the molecular cloning,
      from E. histolytica genomic DNA, of the genes ehtrxr and ehtrx41, respectively
      coding for thioredoxin reductase (EhTRXR) and thioredoxin (EhTRX41). The genes
      were expressed in Escherichia coli cells, and the corresponding recombinant
      proteins were purified and characterized. EhTRXR catalyzed the NADPH (Km=4.5
      microM)-dependent reduction of 5,5'-dithiobis-(2-nitrobenzoic) acid (Km=1.7 mM),
      EhTRX41 (Km=3.6 microM), and E. coli TRX (Km=4.6 microM). EhTRXR and EhTRX41
      could be assayed as a functional redox pair that, together with peroxiredoxin,
      mediate the NADPH-dependent reduction of hydrogen peroxide and tert-butyl
      hydroperoxide. It is proposed that this detoxifying system could be operative in
      vivo. Results add value to the genome project information and advise
      reconsideration of key metabolic pathways operating in E. histolytica.

PMID- 17448897
TI  - Nucleotide receptor signaling in murine macrophages is linked to reactive oxygen
      species generation.
AB  - Macrophage activation is critical in the innate immune response and can be
      regulated by the nucleotide receptor P2X7. In this regard, P2X7 signaling is not
      well understood but has been implicated in controlling reactive oxygen species
      (ROS) generation by various leukocytes. Although ROS can contribute to microbial
      killing, the role of ROS in nucleotide-mediated cell signaling is unclear. In
      this study, we report that the P2X7 agonists ATP and 3'-O-(4-benzoyl) benzoic ATP
      (BzATP) stimulate ROS production by RAW 264.7 murine macrophages. These effects
      are potentiated in lipopolysaccharide-primed cells, demonstrating an important
      interaction between extracellular nucleotides and microbial products in ROS
      generation. In terms of nucleotide receptor specificity, RAW 264.7 macrophages
      that are deficient in P2X7 are greatly reduced in their capacity to generate ROS
      in response to BzATP treatment (both with and without LPS priming), thus
      supporting a role for P2X7 in this process. Because MAP kinase activation is key
      for nucleotide regulation of macrophage function, we also tested the hypothesis
      that P2X7-mediated MAP kinase activation is dependent on ROS production. We
      observed that BzATP stimulates MAP kinase (ERK1/ERK2, p38, and JNK1/JNK2)
      phosphorylation and that the antioxidants N-acetylcysteine and ascorbic acid
      strongly attenuate BzATP-mediated JNK1/JNK2 and p38 phosphorylation but only
      slightly reduce BzATP-induced ERK1/ERK2 phosphorylation. These studies reveal
      that P2X7 can contribute to macrophage ROS production, that this effect is
      potentiated upon lipopolysaccharide exposure, and that ROS are important
      participants in the extracellular nucleotide-mediated activation of several MAP
      kinase systems.

PMID- 17448899
TI  - Elemental selenium at nano size possesses lower toxicity without compromising the
      fundamental effect on selenoenzymes: comparison with selenomethionine in mice.
AB  - Glutathione peroxidase and thioredoxin reductase are major selenoenzymes through
      which selenium exerts powerful antioxidant effects. Selenium also elicits pro
      oxidant effects at toxic levels. The antioxidant and pro-oxidant effects, or
      bioavailability and toxicity, of selenium depend on its chemical form.
      Selenomethionine is considered to be the most appropriate supplemental form due
      to its excellent bioavailability and lower toxicity compared to various selenium
      compounds. The present studies reveal that, compared with selenomethionine,
      elemental selenium at nano size (Nano-Se) possesses equal efficacy in increasing
      the activities of glutathione peroxidase and thioredoxin reductase but has much
      lower toxicity as indicated by median lethal dose, acute liver injury, and short
      term toxicity. Our results suggest that Nano-Se can serve as an antioxidant with
      reduced risk of selenium toxicity.

PMID- 17448898
TI  - Antioxidants improve antibacterial function in hyperoxia-exposed macrophages.
AB  - Hyperoxia and pulmonary infections are well known to increase the risk of acute
      and chronic lung injury in newborn infants, but it is not clear whether hyperoxia
      directly increases the risk of pneumonia. The purpose of this study was to
      examine: (1) the effects of hyperoxia and antioxidant enzymes on inflammation and
      bacterial clearance in mononuclear cells and (2) developmental differences
      between adult and neonatal mononuclear cells in response to hyperoxia. Mouse
      macrophages were exposed to either room air or 95% O2 for 24 h and then incubated
      with Pseudomonas aeruginosa. After 1 h, bacterial adherence, phagocytosis, and
      macrophage inflammatory protein (MIP)-1alpha production were analyzed. Bacterial
      adherence increased 5.8-fold (p < 0.0001), phagocytosis decreased 60% (p < 0.05),
      and MIP-1alpha production increased 49% (p < 0.05) in response to hyperoxia.
      Overexpression of MnSOD or catalase significantly decreased bacterial adherence
      by 30.5%, but only MnSOD significantly improved bacterial phagocytosis and
      attenuated MIP-1alpha production. When monocytes from newborns and adults were
      exposed to hyperoxia, phagocytosis was impaired in both groups. However, adult
      monocytes were significantly more impaired than neonatal monocytes. Data indicate
      that hyperoxia significantly increases bacterial adherence while impairing
      function of mononuclear cells, with adult cells being more impaired than neonatal
      cells. MnSOD reduces bacterial adherence and inflammation and improves bacterial
      phagocytosis in mononuclear cells in response to hyperoxia, which should minimize
      the development of oxidant-induced lung injury as well as reducing nosocomial
      infections.

PMID- 17448900
TI  - Increased affinity for copper mediated by cysteine 111 in forms of mutant
      superoxide dismutase 1 linked to amyotrophic lateral sclerosis.
AB  - Mutations in Cu,Zn-superoxide dismutase (SOD1) cause familial amyotrophic lateral
      sclerosis (ALS). It has been proposed that neuronal cell death might occur due to
      inappropriately increased Cu interaction with mutant SOD1. Using Cu immobilized
      metal-affinity chromatography (IMAC), we showed that mutant SOD1 (A4V, G85R, and
      G93A) expressed in transfected COS7 cells, transgenic mouse spinal cord tissue,
      and transformed yeast possessed higher affinity for Cu than wild-type SOD1.
      Serine substitution for cysteine at the Cys111 residue in mutant SOD1 abolished
      the Cu interaction on IMAC. C111S substitution reversed the accelerated
      degradation of mutant SOD1 in transfected cells, suggesting that the Cys111
      residue is critical for the stability of mutant SOD1. Aberrant Cu binding at the
      Cys111 residue may be a significant factor in altering mutant SOD1 behavior and
      may explain the benefit of controlling Cu access to mutant SOD1 in models of
      familial ALS.

PMID- 17448901
TI  - Inhibition of protein tyrosine phosphatases by amino acid, peptide, and protein
      hydroperoxides: potential modulation of cell signaling by protein oxidation
      products.
AB  - Reaction of radicals in the presence of O2, or singlet oxygen, with some amino
      acids, peptides, and proteins yields hydroperoxides. These species are key
      intermediates in chain reactions and protein damage. They can be detected in
      cells and are poorly removed by enzymatic defenses. Previously we have shown that
      peptide and protein hydroperoxides react rapidly with thiols, with this resulting
      in inactivation of some thiol-dependent enzymes. In light of these data, we
      hypothesized that inactivation of protein tyrosine phosphatases (PTPs), by
      hydroperoxides present on oxidized proteins, may contribute to cellular and
      tissue dysfunction by modulation of phosphorylation-dependent cell signaling. We
      show here that PTPs in cell lysates, and purified PTP-1B, are inactivated by
      amino acid, peptide, and protein hydroperoxides in a concentration- and structure
      dependent manner. Protein hydroperoxides are particularly effective, with
      inhibition occurring with greater efficacy than with H2O2. Inactivation involves
      reaction of the hydroperoxide with the conserved active-site Cys residue of the
      PTPs, as evidenced by hydroperoxide consumption measurements and a diminution of
      this effect on blocking the Cys residue. This inhibition of PTPs, by oxidized
      proteins containing hydroperoxide groups, may contribute to cellular dysfunction
      and altered redox signaling in systems subject to oxidative stress.

PMID- 17448902
TI  - Mutagenic effects of 8-hydroxy-dGTP in live mammalian cells.
AB  - The mutagenicity of an oxidized form of dGTP, 8-hydroxy-2'-deoxyguanosine 5'
      triphosphate (8-OH-dGTP), was examined using COS-7 cells. 8-OH-dGTP and supF
      shuttle plasmid DNA were cointroduced by means of cationic liposomes, and 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 COS-7 cells. This
      result agrees with previous observations indicating that DNA polymerases
      misincorporate 8-OH-dGTP opposite A in vitro, and that the oxidized
      deoxyribonucleotide induces A:T-->C:G transversions in E. coli. These results
      constitute the first direct evidence to show that 8-OH-dGTP actually induces
      mutations in living mammalian cells.

PMID- 17448903
TI  - Oxidative stress and protease dysfunction in the yeast model of Friedreich
      ataxia.
AB  - Friedreich ataxia has frequently been associated with an increased susceptibility
      to oxidative stress. We used the yeast (Saccharomyces cerevisiae) model of
      Friedreich ataxia to study the physiological consequences of a shift from
      anaerobiosis to aerobiosis. Cells lacking frataxin (Deltayfh1) showed no growth
      defect when cultured anaerobically. Under these conditions, a significant amount
      of aconitase was functional, with an intact 4 Fe/4 S cluster. When shifted to
      aerobic conditions, aconitase was rapidly degraded, and oxidatively modified
      proteins (carbonylated and HNE-modified proteins) accumulated in both the cytosol
      and the mitochondria. The ATP-dependent mitochondrial protease Pim1 (Lon) was
      strongly activated, although its expression level remained unchanged, and the
      cytosolic activity of the 20S proteasome was greatly decreased, compared to that
      in wild-type cells. Analysis of the purified proteasome revealed that the
      decrease in proteasome activity was likely due to both direct inactivation of the
      enzyme and inhibition by cytosolic oxidized proteins. These features indicate
      that the cells were subjected to major oxidative stress triggered by oxygen.
      Accumulation of oxidatively modified proteins, activation of Pim1, and proteasome
      inhibition did not directly depend on the amount of mitochondrial iron, because
      these phenotypes remained unchanged when the cells were grown under iron-limiting
      conditions, and these phenotypes were not observed in another mutant (Deltaggc1)
      which overaccumulates iron in its mitochondrial compartment. We conclude that
      oxygen is primarily involved in generating the deleterious phenotypes that are
      observed in frataxin-deficient yeast cells.

PMID- 17448904
TI  - Manganese porphyrin reduces renal injury and mitochondrial damage during
      ischemia/reperfusion.
AB  - Renal ischemia/reperfusion (I/R) injury often occurs as a result of vascular
      surgery, organ procurement, or transplantation. We previously showed that renal
      I/R results in ATP depletion, oxidant production, and manganese superoxide
      dismutase (MnSOD) inactivation. There have been several reports that
      overexpression of MnSOD protects tissues/organs from I/R-related damage, thus a
      loss of MnSOD activity during I/R likely contributes to tissue injury. The
      present study examined the therapeutic benefit of a catalytic antioxidant,
      Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)),
      using the rat renal I/R model. This was the first study to examine the effects of
      MnTnHex-2-PyP(5+) in an animal model of oxidative stress injury. Our results
      showed that porphyrin pretreatment of rats for 24 h protected against ATP
      depletion, MnSOD inactivation, nitrotyrosine formation, and renal dysfunction.
      The dose (50 microg/kg) used in this study is lower than doses of various types
      of antioxidants commonly used in animal models of oxidative stress injuries. In
      addition, using novel proteomic techniques, we identified the ATP synthase-beta
      subunit as a key protein induced by MnTnHex-2-PyP(5+) treatment alone and complex
      V (ATP synthase) as a target of injury during renal I/R. These results showed
      that MnTnHex-2-PyP(5+) protected against renal I/R injury via induction of key
      mitochondrial proteins that may be capable of blunting oxidative injury.

PMID- 17448905
TI  - Redox regulation of 7-ketocholesterol-induced apoptosis by beta-carotene in human
      macrophages.
AB  - The aim of this study was to verify the hypothesis that beta-carotene may prevent
      7-ketocholesterol (7-KC)-induced apoptosis in human macrophages. Therefore, THP-1
      macrophages were exposed to 7-KC (5-50 microM) alone and in combination with beta
      carotene (0.25-1 microM). 7-KC inhibited the growth of macrophages in a dose- and
      a time-dependent manner by inducing an arrest of cell cycle progression in the
      G0/G1 phase and apoptosis. Concomitantly, p53, p21, and Bax expressions were
      increased by 7-KC, whereas the levels of AKT, Bcl-2, and Bcl-xL were decreased.
      beta-Carotene prevented the growth-inhibitory effects of 7-KC in a dose- and time
      dependent manner as well as the effects of 7-KC on the expression of cell cycle-
      and apoptosis-related proteins. 7-KC also enhanced reactive oxygen species (ROS)
      production through an increased expression of NAD(P)H oxidase (NOX-4). The
      effects of 7-KC were counteracted by the addition of the NAD(P)H oxidase
      inhibitor DPI or by cotransfection of siNOX-4 mRNA. beta-Carotene prevented 7-KC
      induced increase in ROS production and in NOX-4 expression, as well as the
      phosphorylation of p38, JNK, and ERK1/2 induced by 7-KC. These data suggest a
      possible antiatherogenic role of beta-carotene through the prevention of 7-KC
      toxicity in human macrophages.

PMID- 17448906
TI  - Impact of iron and vitamin C-containing supplements on preterm human milk: in
      vitro.
AB  - Stress due to reactive oxygen species (ROS) may lead to neonatal diseases, such
      as necrotizing enterocolitis and respiratory distress. Enteral supplements for
      premature infants (PREM) added to human milk (HM) to increase nutrient content
      may induce lipid oxidation due to free radical formation via Fenton chemistry. We
      hypothesized that ferrous iron and vitamin C-containing supplements added to HM
      in vitro cause oxidation of milk fats, affect intracellular redox balance, and
      induce DNA damage. Lipid peroxidation in HM was measured by FOX-2 and TBARS
      assays; fatty acid composition of supplemented HM was measured by gas
      chromatography. Two cell culture bioassays were used for assessing either
      intracellular oxidative stress or DNA damage: the former involved Caco-2BBe
      cells, a secondary differentiated cell line, and the latter utilized FHS-74 Int
      cells, a primary fetal small intestinal culture. Lipid oxidation products of HM
      increased after the addition of iron alone, iron and vitamin C, or iron and a
      vitamin C-containing supplement (Trivisol, TVS). A reduced content of mono and
      polyunsaturated fatty acids in HM was also observed. Iron, not iron+vitamin C,
      but iron+TVS induced significant intracellular oxidative stress in FHS-74 Int
      cells. In contrast, iron, either alone or in combination with TVS or vitamin C,
      increased DNA damage in Caco-2BBE cells. Iron supplementation may increase
      oxidative stress in PREM infants and should be given separately from vitamin C
      containing supplements.

PMID- 17448907
TI  - FLIP inhibits endothelial cell apoptosis during hyperoxia by suppressing Bax.
AB  - High oxygen tension (hyperoxia) causes pulmonary cell death, involving apoptosis,
      necrosis, or mixed death phenotypes, though the underlying mechanisms remain
      unclear. In mouse lung endothelial cells (MLEC) hyperoxia activates both
      extrinsic (Fas-dependent) and intrinsic (mitochondria-dependent) apoptotic
      pathways. We examined the hypothesis that FLIP, an inhibitor of caspase-8, can
      protect endothelial cells against the lethal effects of hyperoxia. Hyperoxia
      caused the time-dependent downregulation of FLIP in MLEC. Overexpression of FLIP
      attenuated intracellular reactive oxygen species generation during hyperoxia
      exposure, by downregulating extracellular-regulated kinase-1/2 activation and
      p47(phox) expression. FLIP prevented hyperoxia-induced trafficking of the death
      inducing signal complex from the Golgi apparatus to the plasma membrane.
      Furthermore, FLIP blocked the activations of caspase-8/Bid, caspases -3/-9, and
      inhibited the mitochondrial translocation and activation of Bax, resulting in
      protection against hyperoxia-induced cell death. Under normoxic conditions, FLIP
      expression increased the phosphorylation of p38 mitogen-activated protein kinase
      leading to increased phosphorylation of Bax during hyperoxic stress. Furthermore,
      FLIP expression markedly inhibited protein kinase C activation and expression of
      distinct protein kinase C isoforms (alpha, eta, and zeta), and stabilized an
      interaction of PKC with Bax. In conclusion, FLIP exerted novel inhibitory effects
      on extrinsic and intrinsic apoptotic pathways, which significantly protected
      endothelial cells from the lethal effects of hyperoxia.

PMID- 17448908
TI  - NADPH oxidase- and mitochondrion-derived superoxide at rostral ventrolateral
      medulla in endotoxin-induced cardiovascular depression.
AB  - We evaluated the contribution of superoxide anion (O2*-) generated by NADPH
      oxidase or mitochondria in the rostral ventrolateral medulla (RVLM), where
      sympathetic premotor neurons for arterial pressure maintenance are located, on
      cardiovascular depression induced by inducible nitric oxide synthase-derived NO
      after Escherichia coli lipopolysaccharide (LPS) treatment. In Sprague-Dawley rats
      maintained under propofol anesthesia, microinjection of LPS bilaterally into the
      RVLM induced progressive hypotension, bradycardia, and reduction in sympathetic
      vasomotor outflow over our 240-min observation period. This was accompanied by an
      increase in O2*- production (60-240 min) in the RVLM, alongside phosphorylation
      of p47(phox) or p67(phox), upregulation of gp91(phox) or p47(phox) protein, and
      increase in Rac-1 or NADPH oxidase activity (60-120 min), and a depression of
      mitochondrial respiratory enzyme activity (120-240 min). Whereas inhibition of
      NADPH oxidase or knockdown of the gp91(phox) or p47(phox) gene blunted the early
      phase (60-150 min), coenzyme Q10 or mitochondrial K(ATP) channel inhibitor
      antagonized the delayed phase (120-240 min) of LPS-induced increase in O2*-
      production in RVLM and cardiovascular depression. We conclude that, whereas NADPH
      oxidase-derived O2*- in RVLM participates predominantly in the early phase, O2*-
      generated by depression in mitochondrial respiratory enzyme activity or opening
      of mitoK(ATP) channels mediates the delayed phase of LPS-induced cardiovascular
      depression.

PMID- 17448909
TI  - Allogeneic stem cell transplantation for aplastic anemia.
AB  - Aplastic anemia encompasses a heterogeneous group of diseases with distinct
      pathophysiologies and a common clinical endpoint of marrow failure. Patients with
      severe aplastic anemia can be treated with immunosuppressive therapy (IST) or
      hematopoietic stem cell transplantation (HSCT). Over the last 30 years, advances
      in both treatment modalities have significantly improved the prognosis for this
      disease; yet this evolution complicates the central therapeutic question in
      aplastic anemia: which patients should receive IST and which ones should receive
      HSCT as front-line therapy? In this review, we describe the major improvements
      that have occurred in transplantation for aplastic anemia in the last 3 decades.
      We then outline a framework for deciding which patients should be considered for
      upfront transplantation.

PMID- 17448910
TI  - Increased risk of bone loss without fracture risk in long-term survivors after
      allogeneic stem cell transplantation.
AB  - We studied bone mineral density (BMD) in 79 long-term survivors of allogeneic
      stem cell transplantation (SCT) (median follow-up: 78 months; range: 38-160).
      Seventy patients received a total body irradiation (TBI)-based myeloablative SCT
      and 9 patients received a non-TBI, reduced-intensity SCT. Fourteen (18%) patients
      were receiving immunosuppressive therapy (IST) for chronic graft-versus-host
      disease (cGVHD) beyond 3 years from SCT. Fifty-eight (73.4%) of patients had bone
      loss (BL): 33 (41.8%) with osteopenia and 25 (31.6%) with osteoporosis. Factors
      associated with a significantly increased risk of osteoporosis were age and
      prolonged IST and for overall BL prolonged IST. However, BL was not associated
      with an increased fracture risk, despite the fact that most patients had not
      received prophylactic biphosphonates. Our data shows that BL is a long-term
      posttransplant complication, and emphasize the importance of serial BMD scans,
      and the treatment of BL with biphosphonates reserved for worsening BL or
      additional risk factors.

PMID- 17448912
TI  - Elevation of intracellular cyclic AMP in alloreactive CD4(+) T Cells induces
      alloantigen-specific tolerance that can prevent GVHD lethality in vivo.
AB  - Cyclic AMP (cAMP) is an important negative regulator of T cell activation, and an
      increased level of cAMP is associated with T cell hyporesponsiveness in vitro. We
      sought to determine whether elevating intracellular cAMP levels ex vivo in
      alloreactive T cells during primary mixed lymphocyte reactions (MLR) is
      sufficient to induce alloantigen-specific tolerance and prevent graft-versus-host
      disease (GVHD). Primary MLRs were treated with exogenous (8)Br-cAMP and IBMX, a
      compound that increases intracellular cAMP levels by inhibition of
      phosphodiesterases. T cell proliferation and IL-2 responsiveness in the treated
      primary MLR cultures were greatly reduced, and viable T cells recovered on day 8
      also had impaired responses to restimulation with alloantigen compared to control
      treated cells, but without an impairment to nonspecific mitogens. Labeling
      experiments showed that cAMP/IBMX inhibited alloreactive T cell proliferation by
      limiting the number of cell divisions, increasing susceptibility to apoptosis,
      and rendering nondeleted alloreactive T cells hyporesponsive to alloantigen
      restimulation. cAMP/IBMX-treated CD4(+) T cells had a markedly reduced capacity
      for GVHD lethality in major histocompatibility complex class II disparate
      recipients, but maintained the capacity to mediate other CD4(+) T cell responses
      in vivo. Thus, our results provide the first preclinical evidence of using cAMP
      elevating pharmaceutical reagents to achieve long-term alloantigen-specific T
      cell tolerance that is sufficient to prevent GVHD.

PMID- 17448911
TI  - The synthetic triterpenoid, CDDO, suppresses alloreactive T cell responses and
      reduces murine early acute graft-versus-host disease mortality.
AB  - Acute graft-versus-host disease (aGVHD) still remains one of the life-threatening
      complications following allogeneic hematopoietic stem cell transplantation (allo
      HSCT). Immunomodulation of alloreactive donor T cell responses, as well as
      cytokine secretion is a potential therapeutic approach for the prevention of
      aGVHD. The synthetic triterpenoid, CDDO (2-cyano-3, 12-dioxooleana-1, 9-dien-28
      oic acid), exhibits potent antitumor activity and has also been shown to mediate
      anti-inflammatory and immunomodulatory effects. We therefore wanted to assess the
      effects of CDDO on early lethal aGVHD. In this study, we found that CDDO
      significantly inhibited in vitro mixed lymphocyte responses and preferentially
      promoted the apoptosis of proliferating but not resting alloreactive T cells.
      Using a full major histocompatibility complex (MHC)-disparate murine aGVHD model,
      we found that the administration of CDDO immediately after transplantation
      significantly decreased liver pathology as determined by histologic assessment
      and prolonged survival in mice. Importantly, administration of CDDO did not
      adversely impair donor myeloid reconstitution as determined by peripheral blood
      cell count and the extent of donor chimerism. These findings indicate that CDDO
      has a significant immunomodulatory effects in vitro and on early lethal aGVHD
      development, particularly affecting the liver, in a murine allo-HSCT model.

PMID- 17448913
TI  - Results of a retrospective single institution analysis of targeted skeletal
      radiotherapy with (166)Holmium-DOTMP as conditioning regimen for autologous stem
      cell transplant for patients with multiple myeloma. Impact on transplant
      outcomes.
AB  - (166)Holmium-DOTMP is a beta-emitting radiophosphonate that localizes
      specifically to the bone surfaces and can deliver high-dose radiation to the bone
      marrow. Phase I/II trials showed feasibility and tolerability when combined with
      high-dose melphalan with or without total-body irradiation (TBI) in patients with
      multiple myeloma (MM) undergoing autologous stem cell transplantation (ASCT). The
      purpose of this study was to define the potential impact of (166)Holmium-DOTMP on
      outcomes in patients with MM undergoing ASCT. Retrospective review of transplant
      outcomes among patients with MM who received an ASCT between January 1998 to
      December 2001 with either melphalan 200 mg/m(2) or a (166)Holmium-DOTMP
      containing regimen as part of their initial therapy. Univariate analysis was
      performed for response, overall survival (OS), and event free survival (EFS). One
      hundred four patients were identified, of which 41 received a (166)Holmium-DOTMP
      containing regimen and 63 received melphalan alone. The (166)Holmium-DOTMP
      patients were divided into 2 groups according to the dose received (<2400 mCi
      versus > or = 2400 mCi). The (166)Holmium-DOTMP group had a trend towards a
      higher complete remission (CR) rate compared to patients receiving melphalan
      alone (51% versus 32%). The median EFS for the low-dose (166)Holmium-DOTMP, the
      high-dose (166)Holmium-DOTMP, and melphalan alone was 30, 23, and 19 months,
      respectively; the OS rate at 5 years for the 3 groups was 61%, 40%, and 43%,
      respectively. (166)Holmium-DOTMP, in combination with high-dose melphalan, can
      result in higher CR rates when given in optimal doses (<2400 mCi) when compared
      to melphalan alone, and should be further tested in phase III trials in patients
      with MM undergoing ASCT.

PMID- 17448914
TI  - The impact of chimerism patterns and predonor leukocyte infusion lymphopenia on
      survival following T cell-depleted reduced intensity conditioned transplants.
AB  - Donor leukocyte infusions (DLI) are frequently required following reduced
      intensity conditioned (RIC) allografts to convert mixed chimerism (MC) to full
      donor chimerism (FDC). The rationale is to break tolerance and maximize the graft
      versus-leukemia responses. We analyzed the impact of chimerism in 125 recipients
      of RIC (Alemtuzumab containing) transplants. Four patterns of chimerism were
      seen: (1) always 100% donor chimerism (54%), (2) persisting MC (22%), (3) MC with
      subsequent development of FDC (18%), (4) lost donor chimerism (6%). Forty-five
      (36%) patients received DLI. Chimerism patterns and pre-DLI lymphocyte counts
      (pDLI[Ly]) were significantly associated with DLI responsiveness. Complete
      disease responses were seen in 6 of 17 (35%) group A patients, 9 of 10 (90%)
      group C patients, and 0 of 6 group B patients (P = .027), supporting reports that
      chimerism response is a surrogate marker for disease response. In those with MC,
      pDLI(Ly) were significantly lower in DLI responsive than nonresponsive patients
      (P = .044). At 2 years, group C patients had a significant survival advantage (P
      = .009) compared to all other groups. In conclusion, the chimerism pattern was
      the best indicator of improved survival in this cohort (ie, MC later converting
      to FDC). In those with MC, response to DLI therapy was associated with a low
      lymphocyte count pre-DLI.

PMID- 17448915
TI  - A prospective multicenter trial of peripheral blood stem cell sibling allografts
      for acute myeloid leukemia in first complete remission using fludarabine
      cyclophosphamide reduced intensity conditioning.
AB  - The role of allogeneic transplantation in patients with de novo acute myeloid
      leukemia in first complete remission (AML-CR1) is controversial. Aiming to
      preserve a graft-versus-leukemia effect, but minimize morbidity and mortality
      from conditioning-related toxicity and graft-versus-host disease (GVHD), we
      conducted a prospective multicenter study of reduced-intensity conditioning (RIC)
      as preparation for peripheral blood stem cell sibling allografts in patients with
      intermediate or poor risk AML-CR1. Conditioning consisted of fludarabine 125
      mg/m(2) and cyclophosphamide 120 mg/kg. Thirty-four patients were transplanted
      with a median age of 45 years; 85% had intermediate risk cytogenetics. Early
      toxicity was minimal. The overall incidence of grade II-IV acute GVHD was low
      (21%), but the 3 patients (9%) who developed grade IV GVHD died. Donor T cell
      chimerism was rapid and generally complete, but complete myeloid chimerism was
      delayed. Thirteen patients (38%) relapsed, 12 within a year of transplant. The
      estimated disease-free survival (DFS) and overall survival at 2 years was 56%
      (95% confidence interval [CI] 39%-71%) and 68% (95% CI 50%-81%), respectively.
      The incidence of extensive chronic GVHD (cGVHD) was low (24% of surviving
      patients at 12 months) and most survivors had an excellent performance status.
      These observations justify a prospective comparison of RIC versus myeloablative
      conditioning allografts for AML-CR1.

PMID- 17448916
TI  - Observation-based early warning scores to detect impending critical illness
      predict in-hospital and overall survival in patients undergoing allogeneic stem
      cell transplantation.
AB  - Observation-based early warning scoring systems (EWSS) have been developed to
      improve the outcome of critically ill patients by triggering early critical care
      intervention. To date, none of these scoring systems have been evaluated in
      cancer patients or stem cell transplant (SCT) recipients. The aim of this study
      was to validate 3 established EWSS (modified early warning score [MEWS], patient
      at-risk score [PARS], and Leed's early warning score [LEWS]) in adult recipients
      of Allogeneic SCT (Allo-SCT) and to determine their usefulness at predicting
      survival. We retrospectively analyzed the physiologic observations during the
      initial admission of 43 Allo-SCT recipients. Respiratory dysfunction was the most
      common (40 patients, 93%) event. All 3 EWSS revealed high accuracy in predicting
      in-hospital survival. The cutoff level associated with a high risk of in-hospital
      mortality was 7. Of 8 patients with a LEWS = 7, 6 died during their initial
      admission, whereas no patient with a lower score died (specificity 95%,
      sensitivity 100%). Acute clinical deterioration during the initial admission
      appeared to have an adverse effect on overall survival: in-hospital survivors
      with a LEWS >3 during their admission had a shorter median survival than patients
      with LEWS < or = 3, P = .018. This is the first study to validate EWSS in Allo
      SCT and demonstrate that these systems are highly predictive of in-hospital and
      overall survival.

PMID- 17448917
TI  - Cytomegalovirus infections following umbilical cord blood transplantation using
      reduced intensity conditioning regimens for adult patients.
AB  - Cytomegalovirus (CMV) infection is a major complication after allogeneic
      hematopoietic stem cell transplantation (Allo-HSCT); however, we have little
      information on the clinical features of CMV reactivation after cord blood
      transplantation using reduced-intensity regimens (RI-CBT) for adults. We reviewed
      medical records of 140 patients who underwent RI-CBT at Toranomon Hospital
      between January 2002 and March 2005. All the patients were monitored for CMV
      antigenemia weekly, and, if turned positive, received preemptive foscarnet or
      ganciclovir. Seventy-seven patients developed positive antigenemia at a median
      onset of day 35 (range, 4-92) after transplant. Median of the maximal number of
      CMV pp65-positive cells per 50,000 cells was 22 (range, 1-1806). CMV disease
      developed in 22 patients on a median of day 35 (range, 15-106); 21 had
      enterocolitis and 1 had adrenalitis. CMV antigenemia had not been detected in 2
      patients, when CMV disease was diagnosed. CMV disease was successfully treated
      using ganciclovir or foscarnet in 14 patients. The other 8 patients died without
      improvement of CMV disease. In multivariate analysis, grade II-IV acute graft
      versus-host disease was a risk factor of CMV disease (relative risk 3.48, 95%
      confidential interval 1.47-8.23). CMV reactivation and disease develop early
      after RI-CBT. CMV enterocolitis may be a common complication after RI-CBT.

PMID- 17448918
TI  - The effects of Campath 1H upon graft-versus-host disease, infection, relapse, and
      immune reconstitution in recipients of pediatric unrelated transplants.
AB  - Graft-versus-host disease (GVHD) is a cause of serious morbidity and mortality in
      >50% of recipients of unrelated hematopoietic stem cell transplantation (HSCT).
      We performed a trial using Campath 1 H pre- and post-HSCT in an attempt to
      decrease the incidence of GVHD without increasing the risk of infection or
      relapse. Patients were retrospectively compared to a population of patients who
      received antithymocyte globulin (ATG) pre- and post-HSCT. Twenty-seven patients
      were evaluated for this study. Fourteen patients received Campath 1H and 13
      patients received ATG. Demographics of patients who received Campath 1H consisted
      of 9 males and 5 females, with a median age of 13 years (3-17.8 years). Thirteen
      patients received unrelated bone marrow and 1 patient received unrelated PBSC.
      Demographics of patients receiving ATG consisted of 9 males, 4 females with a
      median age of 7.4 years (21 months-19 years). Twelve patients received unrelated
      bone marrow and 1 patient received unrelated PBSC. Diagnoses were similar between
      the 2 groups. Patients who received Campath1H received a total dose of 52 mg/m(2)
      pre-HSCT and 20 mg/m(2) post-HSCT. Patients who received ATG received a total
      dose of 60 mg/kg pre-HSCT and 100 mg/kg post-HSCT. GVHD prophylaxis and
      supportive care measures were similar in both groups, including aggressive
      antimicrobial therapy. There was a significant difference in the incidence of
      severe (grade III and grade IV) GVHD between the 2 groups (Campath [0 of 14]
      versus ATG [6 of 13], P = .006). Among the patients who were transplanted for
      leukemia, there was no significant difference between the 2 groups in terms of
      relapse (Campath [2 of 14] versus ATG [4 of 9], P = 0.16). The 100-day survival
      between the 2 groups was not significantly different. Patients receiving Campath
      1H had the presence of CD3(+) T cells (>30 cells/mL) in their peripheral blood
      later than in those who received ATG (64.5 days [Campath 1H] versus 27days [ATG],
      P = .001). The median time to the development of a normal PHA response occurred
      later in the Campath 1H arm (283 days[(Campath 1H] versus 88 days [ATG], P =
      .0001). The median time to an antigen specific response also occurred later in
      those receiving Campath 1H (365 days [Campath 1H] versus 150 days [ATG], P =
      .004). There was no significant difference between the 2 groups in terms of
      fungal or viral infections. Campath 1H is effective in decreasing the incidence
      of GVHD without increasing the risk of relapse. Although there is a significant
      delay in immune reconstitution, there was no increase in infectious complications
      or relapse in recipients of Campath 1H. Further studies are warranted to assess
      if a lack of difference in infection rates are still demonstrated in larger
      cohorts.

PMID- 17448919
TI  - Tandem autologous stem cell transplantation for patients with primary refractory
      or poor risk recurrent Hodgkin lymphoma.
AB  - Although autologous stem cell transplantation (ASCT) for patients with
      relapsed/refractory Hodgkin lymphoma (HL) appears to offer a survival advantage
      over conventional therapy, only approximately 25% to 35% of patients with primary
      progressive or poor-risk recurrent HL can achieve durable remission after ASCT,
      with disease progressive after transplant accounting for most of the treatment
      failures. We conducted a pilot study to evaluate the toxicities and efficacy of a
      tandem transplant approach in this subgroup of patients. Between April 1998 and
      March 2000, 46 patients were enrolled in the study. ELIGIBILITY CRITERIA: primary
      progressive (n = 28) or recurrent HL (n = 18) with at least 1 of the following
      poor prognostic factors: first complete remission (CR) <12 months (n = 15) or
      extra-nodal disease (n = 4) or B symptoms at relapse (n = 4). The first cycle
      consisted of melphalan (150 mg/m(2)) alone. The second cycle consisted of
      fractionated total body irradiation (FTBI) 1200 cGy or BCNU (450 mg/m(2)) in
      combination with etoposide (60 mg/kg) and cyclophosphamide (100 mg/kg). Of the 46
      patients, 5 (11%) did not receive the planned tandem transplants because of
      inadequate stem cell collection for 2 ASCT. After a median of 64 days (25-105),
      41 patients received the second ASCT. With a median follow-up of 5.3 years (1.6
      8.1), the 5-year estimate of overall survival, progression-free survival, and
      freedom from progression were 54% (95% confidence interval [CI] 40%-69%), 49%
      (95% CI, 34%-63%), and 55% (95%CI, 40%-70%), respectively. Our mature results
      from this study suggest that in patients with primary progressive or poor risk
      recurrent HL, this tandem ASCT program is effective and well tolerated and
      compares favorably with the conventional single transplant.

PMID- 17448920
TI  - Equivalent survival for sibling and unrelated donor allogeneic stem cell
      transplantation for acute myelogenous leukemia.
AB  - Recent studies have shown comparable survival outcomes for unrelated donor (URD)
      stem cell transplantation in chronic myelogenous leukemia compared to sibling
      donors. We compared outcomes for 105 patients aged 16 to 59 years undergoing URD
      transplants for acute myelogenous leukemia (AML) who were reported to the
      Australasian Bone Marrow Transplant Recipient Registry between 1992 and 2002, and
      a strictly selected matching set of 105 HLA-matched sibling donor (MSD)
      transplants. There was no significant difference between URD and MSD controls in
      the distributions of time from diagnosis to transplant, donor-recipient sex
      match, prior therapies, donor age, or performance status. The median follow-up of
      live URD patients was 4.4 years and for live MSD controls was 6.3 years. There
      were 18 good risk (complete remission [CR]1) and 87 poor risk (>CR1) recipients
      in both URD and sibling groups. Five-year disease-free survival (DFS) was not
      significantly different for good-risk URD and sibling donor recipients (62%
      versus 40%, P = .2), or poor-risk URD and sibling recipients (21% versus 25%, P =
      .2). In a stratified multivariate Cox regression model, the independent adverse
      risk factors for DFS were recipient cytomegalovirus positivity (P = .01) and the
      interaction of URD and earlier year of transplant (P = .006). Both neutrophil and
      platelet engraftment were significantly more rapid in the sibling group, but
      transplant-related mortality at 100 days was not significantly different. There
      was no difference in the cumulative incidence of acute graft-versus-host disease
      grade II or above at 100 days. Relapse occurred in 28% of good risk URD subjects
      and 16% of siblings (P = .3), and in poor risk subjects 39% and 29%, respectively
      (P = .2). Based on this data, URD allografts should be considered in AML patients
      without a matched sibling donor. This study provides a rationale for a larger
      prospective study of risk factors in allogeneic transplantation for AML and a
      guide on the subset of patients who may most benefit from an unrelated donor
      allograft in AML.

PMID- 17448921
TI  - CD34(+) hematopoietic progenitor cell selection of bone marrow grafts for
      autologous transplantation in pediatric patients.
AB  - CD34(+)-selection of hematopoietic grafts for patients undergoing autologous
      hematopoietic stem cell transplantation (HSCT) is frequently used to obtain a
      tumor-free graft. The majority of published experience is with peripheral blood
      stem cell (PBSC) products; only scant information has been published on bone
      marrow (BM) grafts. We reviewed our experience using CD34(+) selection of BM
      grafts in children undergoing autologous BM transplantation. After obtaining
      institutional approval, we performed a retrospective review of the medical
      records of patients who underwent autologous stem cell collection at St. Jude.
      From January 1, 1999, to December 31, 2003, 373 patients underwent autologous
      HSCT; 131 received marrow grafts, 237 received PBSC grafts, and 5 received a
      combination. Seventeen patients underwent BM harvests for CD34(+) selection of
      their stem cell grafts. Sixteen patients received 19 CD34 purified grafts
      processed on the Isolex 300i Magnetic Cell Selection System device. Four patients
      were not included in the engraftment analysis as 1 did not receive the collected
      product, 1 received a tandem product, and 2 received products that were composed
      of 2 or 3 combined purified products. Following selection, marrow grafts
      contained a median of 1.4 x 10(6) CD34(+) cells/kg (range: 0.09-8.3 x 10(6)/kg)
      and a median of 0.014 x10(8) total nucleated cell cells/kg (range: 0.001-0.09 x
      10(8)/kg). The median CD34% recovery was 30.9% (range: 9.3%-57.1%), with the
      median CD34 purity being 95.5% (range: 62.2%-98.8%). All patients engrafted. The
      median time to absolute neutrophil count > or = 500/mm(3) was 19 days (range: 12
      35 days), and to platelet recovery was 28 days (range 18-37 days). No patient
      died from transplant-related complications. Our study demonstrates that CD34(+)
      selection of marrow grafts is feasible, and these grafts are able to successfully
      reconstitute hematopoiesis in patients undergoing autologous BMT.

PMID- 17448922
TI  - Colonization, bloodstream infection, and mortality caused by vancomycin-resistant
      enterococcus early after allogeneic hematopoietic stem cell transplant.
AB  - Bloodstream infection caused by vancomycin-resistant enterococcus (VRE) is
      associated with very high mortality among allogeneic hematopoietic stem cell
      transplant (alloHSCT) recipients. However, it remains unclear whether VRE
      bloodstream infection directly causes mortality in the early posttransplant
      period or is simply a marker of poor outcome. To determine the risk factors for
      VRE bloodstream infection and its effect on outcome, we followed 92 patients
      screened for stool colonization by VRE upon admission for alloHSCT. Patient
      records were reviewed to determine outcomes, including mortality and
      microbiologic failure. Colonization by VRE was extremely common, occurring in
      40.2% of patients. VRE bloodstream infection developed in 34.2% of colonized
      patients by day +35, compared to 1.8% without VRE colonization (P < .01). VRE
      bloodstream infection was associated with a significant decrement in survival and
      frequent microbiologic failure, despite treatment with linezolid and/or
      daptomycin. Five (35.7%) of 14 patients with VRE bloodstream infection had
      attributable mortality or contributing mortality from the infection. Strain
      typing by pulsed-field gel electrophoresis identified 9 different VRE strains
      among the 37 colonized patients and 5 patients with different strains recovered
      from the stool and the blood. In conclusion, stool screening effectively
      identified patients at extremely high risk for VRE bloodstream infection. The
      high mortality of VRE in the early posttransplant period supports the use of
      empiric antibiotics with activity against VRE during periods of fever and
      neutropenia in colonized patients.

PMID- 17448923
TI  - Recombinant factor VIIa to treat diffuse alveolar hemorrhage following allogeneic
      stem cell transplantation.

PMID- 17448924
TI  - Autologous stem cell transplantation as part of first-line treatment of
      Waldenstrom's macroglobulinemia.

PMID- 17448926
TI  - Binocular vision and refractive surgery.
AB  - Binocular status can have an effect on the outcome of refractive surgery. Some
      accommodative deviations and anisometropia can be managed effectively. Fully
      accommodative esotropia has been successfully treated in young patients but the
      outcome can be less predictable in older patients. High anisometropes are usually
      unaffected by the change in aniseikonia following refractive surgery but there
      are exceptions. Failure to recognise and appropriately classify a binocular
      vision anomaly pre-surgically can result in symptoms that are difficult to manage
      post-operatively. Refractive surgery producing a binocular vision anomaly where
      there was none pre-operatively is less common. I present a review of the
      literature discussing the relationship between binocular vision anomalies and
      refractive surgery, illustrating the findings with published reports of
      successful and unsuccessful binocular postoperative outcomes. I argue that
      predicting the binocular outcome should be considered pre-operatively for every
      refractive surgery patient.

PMID- 17448927
TI  - Is randomisation necessary for measuring defocus curves in pre-presbyopes?
AB  - PURPOSE: Defocus curves are used to evaluate the subjective range of clear vision
      of presbyopic corrections such as in eyes implanted with accommodating
      intraocular lenses (IOLs). This study determines whether letter sequences and/or
      lens presentation order ought to be randomised when measuring defocus curves.
      METHODS: Defocus curves (range +2.00DS to -2.00DS) were measured on 18 pre
      presbyopic subjects (mean age 24.1+/-4.2 years) for six combinations of
      sequential or randomised positive or negative lens progression and non-randomised
      or randomised letter sequences. The letters were presented on a computerised
      logMAR chart at 6m. RESULTS: Overall there was a statistically significant
      difference between the six combinations (ANOVA, p<0.05) attributable to the
      combination of non-randomised letters with non-randomised lens progression from
      negative to positive defocus (p<0.01). There was no statistically significant
      difference in defocus curve measurements if both letters and lens order were
      randomised compared to if only one of these variables was randomised (p>0.05).
      Non-randomised letters, with a sequential lens progression from negative to
      positive, was significantly different to all other combinations when compared
      individually (Student's T-test, p<0.003 on all comparisons), and was confirmed as
      the sole source of the overall significant difference. There was no statistically
      significant difference if both lens presentation order and letter sequences were
      randomised compared to if only one or the other of these variables was
      randomised. CONCLUSION: Non-randomised letters and non-randomised lens
      progression on their own did not affect the subjective amplitude of accommodation
      as measured by defocus curves, although their combination should be avoided.

PMID- 17448928
TI  - Circumcision and circumspection.

PMID- 17448929
TI  - Hand hygiene and health-care-associated infections.

PMID- 17448930
TI  - Hand hygiene and health-care-associated infections.

PMID- 17448932
TI  - Chikungunya epidemic in India: a major public-health disaster.

PMID- 17448933
TI  - Two cultures.

PMID- 17448935
TI  - Chikungunya, an epidemic arbovirosis.
AB  - Chikungunya is an arboviral disease transmitted by aedes mosquitoes. The virus
      was first isolated in 1953 in Tanzania. Chikungunya virus is a member of the
      genus Alphavirus and the family Togaviridae. The disease typically consists of an
      acute illness characterised by fever, rash, and incapacitating arthralgia. The
      word chikungunya, used for both the virus and the disease, means "to walk bent
      over" in some east African languages, and refers to the effect of the joint pains
      that characterise this dengue-like infection. Chikungunya is a specifically
      tropical disease, but it is geographically restricted and outbreaks are
      relatively uncommon. It is only occasionally observed in travellers and military
      personnel. More than 266 000 people have been infected during the ongoing
      outbreak in Reunion, in which Aedes albopictus is the presumed vector. In the
      ongoing Indian outbreak, in which Aedes aegypti is the presumed vector, 1 400 000
      cases of chikungunya were reported during 2006. The reasons for the re-emergence
      of chikungunya on the Indian subcontinent, and for its unprecedented incidence
      rate in the Indian Ocean region, are unclear. Plausible explanations include
      increased tourism, chikungunya virus introduction into a naive population, and
      viral mutation.

PMID- 17448936
TI  - Global phylogeography of Mycobacterium tuberculosis and implications for
      tuberculosis product development.
AB  - New tools for controlling tuberculosis are urgently needed. Despite our emerging
      understanding of the biogeography of Mycobacterium tuberculosis, the implications
      for development of new diagnostics, drugs, and vaccines is unknown. M
      tuberculosis has a clonal genetic population structure that is geographically
      constrained. Evidence suggests strain-specific differences in virulence and
      immunogenicity in light of this global phylogeography. We propose a strain
      selection framework, based on robust phylogenetic markers, which will allow for
      systematic and comprehensive evaluation of new tools for tuberculosis control.

PMID- 17448937
TI  - Efficacy and safety of cefepime: a systematic review and meta-analysis.
AB  - Cefepime is a broad-spectrum cephalosporin with enhanced coverage against Gram
      positive and Gram-negative bacteria. We did a systematic review of randomised
      trials that compared cefepime with another beta-lactam antibiotic, alone or with
      the addition of a non-beta-lactam antibiotic to both study groups. We searched
      Central, PubMed, Embase, Lilacs, new US Food and Drug Administration drug
      applications, conference proceedings, and references of the included studies. Two
      reviewers independently did the search and data extraction. 57 trials were
      included. All-cause mortality-the primary outcome-was higher with cefepime than
      other beta-lactams (risk ratio [RR] 1.26 [95% CI 1.08-1.49]). Sensitivity
      analyses by the trials' methodological quality revealed higher RRs for trials
      reporting adequate allocation-sequence generation (1.52 [1.20-1.92]) and
      allocation concealment (1.36 [1.09-1.70]). Baseline risk factors for mortality
      were similar. No significant differences between groups in treatment failure,
      superinfection, or adverse events were found. This Review provides evidence and
      offers possible explanations for increased mortality among patients treated with
      cefepime in randomised trials.

PMID- 17448938
TI  - Imported malaria in children: a review of clinical studies.
AB  - Imported malaria is a preventable disease, yet it is responsible for several
      thousand cases and a substantial number of deaths every year. There has been a
      pronounced rise in the incidence of imported malaria in most developed countries
      over the past three decades and, more concerning, Plasmodium falciparum, which is
      responsible for almost all cases of severe malaria, is now the most prevalent
      species. Children account for around 15-20% of all imported malaria cases and
      must be considered separately from adults because they have different risk
      factors for developing malaria and a higher risk of developing severe disease
      since they are more likely to be non-immune to malaria. We did a thorough review
      of the literature since 1980 to identify and critically assess clinical case
      series on children with imported malaria with respect to travel destination,
      reason for travel, the use of antimalarial prophylaxis, clinical presentation,
      delay in diagnosis, laboratory features, complications, management, and outcome.
      Children living in non-endemic countries and travelling during school holidays to
      visit family and relatives in their parents' country of origin currently account
      for the largest proportion of cases in many European countries. This group of
      travellers deserves special attention because they often do not take antimalarial
      prophylaxis or other preventive measures. There is a need for standardised
      recommendations on management and prevention of imported malaria in children,
      which should be supported by large multicentre clinical trials. A prospective
      national surveillance study on imported malaria in children was launched in the
      UK and Ireland through the British Paediatric Surveillance Unit in 2006, which
      may provide answers to some of the questions raised in this Review.

PMID- 17448939
TI  - Statins and sepsis: multiple modifications at multiple levels.
AB  - Sepsis, an infection-induced inflammatory syndrome, is a leading and increasing
      cause of mortality worldwide. Animal and human observational studies suggest
      statins may prevent the morbidity and mortality associated with the sepsis
      syndrome. In this Review, we describe the demonstrated mechanisms through which
      statins modulate the inflammatory response associated with sepsis. These
      mechanisms include effects on cell signalling with consequent changes at the
      transcriptional level, the induction of haem oxygenase, the direct alteration of
      leucocyte-endothelial cell interaction, and the reduced expression of MHC II.
      Since statins do not target individual inflammatory mediators, but possibly
      reduce the overall magnitude of the systemic response, this effect could prove an
      important distinguishing feature modulating the host response to septic insults.
      This work establishes the biological plausibility needed for future trials of
      statins in critical illness.

PMID- 17448940
TI  - World Health Organization and International Travel and Health.

PMID- 17448942
TI  - Clinical manifestations of Q fever in adults and children.
AB  - Q fever is a common zoonosis with almost a worldwide distribution caused by
      Coxiella burnetii. Farm animals and pets are the main reservoirs of infection and
      transmission to humans is usually via inhalation of contaminated aerosols, which
      may be carried by the wind far from the original source of infection.
      Occupational groups with close association with farm or wild animals are most at
      risk, however travellers occasionally become infected. The disease is associated
      with a wide spectrum of clinical manifestations and symptoms, ranging from
      asymptomatic infection to fatal disease. Awareness of the disease and newer
      diagnostic methods led to increase of recognition and detection in cases with
      various or multiple symptoms in adults and children. However, children seem to be
      less frequently symptomatic and may have milder disease. This review of Q fever
      cases examines clinical manifestations and symptoms of Q fever in both adults and
      children and shows that certain symptoms and their severity have altered
      presentation in children with acute and chronic Q fever when compared to adults.

PMID- 17448941
TI  - Cutaneous leishmaniasis treatment.
AB  - The causative species of cutaneous leishmaniasis determines the clinical features
      and courses, and treatments. Intralesional or systemic antimonials are the gold
      standard for the treatment of these diseases. However, as for visceral
      leishmaniasis, other therapeutic options appear promising. Paromomycin ointments
      are effective in Leishmania major, L. tropica, L. mexicana, and L. panamensis
      lesions. In L. braziliensis localized leishmaniasis, both paromomycin and
      imiquimod may be topically applied. Oral fluconazole and zinc sulfate are useful
      in L. major. Oral azithromycin, effective in vitro and in mice, needs further
      investigation in human leishmaniasis. On the contrary, data with oral
      itraconazole are disappointing. Oral miltefosine, which is very effective in
      visceral leishmaniasis caused by L. donovani, appears ineffective in L. major and
      L. braziliensis infections. Intramuscular pentamidine is required for L.
      guyanensis cutaneous leishmaniasis, for which systemic antimony is not effective.
      Liposomal amphotericin B could be an alternative to antimony in south American
      cutaneous leishmaniasis with mucosal involvement (especially L. braziliensis and
      L. guyanensis infections).

PMID- 17448943
TI  - Illness and injury presenting to a Norwegian travel insurance company's helpline.
AB  - INTRODUCTION: Travel abroad is increasing, yet little attention has been paid to
      the use of health services by specific groups of travellers. This study describes
      the prevalence of illness, injury and subsequent changes to homeward bound travel
      and the costs for a group of Norwegian travellers. METHODS: In 2003, 1787 cases
      were registered in the data base of the helpline of Norway's largest insurance
      company. This data were analyzed for prevalence of illness and injury according
      to age, gender, type of illness or injury, travel destination, type of travel,
      and the impact on return travel. RESULTS: Illness and injury accounted for 76.2%
      and 23.8% of the notifications, respectively. Travellers over the age of 60
      accounted for 32.3% of the total number of illnesses. The illness reported most
      frequently was infection (20.3%), with the highest prevalence of infections
      occurring in Southern and Eastern Europe (10.2%). The results obtained in this
      study were compared with studies of other populations of European travellers,
      revealing that infectious diseases are the most prevalent illness. Differences
      were noted in the incidence of cardiovascular disease and the destinations where
      this occurred, and of fatality. CONCLUSION: The results of this study when
      compared with those of other European travellers revealed that sufficient
      difference occurs. As a consequence pre-departure information needs to target
      better specific population groups with respect to minimizing the risk of illness
      and injury. As well, the collection of data by the insurance company misses the
      opportunity of acquiring data of real value for future travellers, the insurance
      company and the medical profession. It is argued that there is a need to develop
      a comprehensive data base of greater use than available currently.

PMID- 17448944
TI  - Ten-year antibody persistence induced by hepatitis A and B vaccine (Twinrix) in
      adults.
AB  - BACKGROUND: Hepatitis A and B infections are prevalent worldwide and cause
      significant morbidity and mortality. A combined vaccine providing dual protection
      against hepatitis A and B is available (Twinrix, GlaxoSmithKline Biologicals).
      METHOD: Two cohorts of adults aged 17-43 years were vaccinated with Twinrix
      according to a 0, 1, 6 months schedule and followed up for 10 years. RESULTS: One
      month after the primary vaccination course (Month 7), all subjects were
      seropositive for anti-HAV and all had anti-HBs> or = 10 mIU/ml. At month 120,
      100% of subjects (N=34; N=29) in both cohorts were seropositive for anti-HAV;
      94.1% and 86.2% of subjects had anti-HBs > or = 10 mIU/ml. The geometric mean
      concentrations (GMC; mIU/ml) were 373.9 and 674.6 in the two cohorts for anti
      HAV, and 103.8 and 320.0, respectively, for anti-HBs. None of the serious adverse
      events reported throughout the follow-up period were considered by the
      investigator to be causally related to vaccination. CONCLUSIONS: Combined
      hepatitis A and B vaccine, Twinrix, is safe, well-tolerated and has demonstrated
      a highly immunogenic profile. Persistence of anti-HAV and anti-HBs antibodies in
      adults remains high for at least 10 years after primary vaccination.

PMID- 17448945
TI  - Travellers to high UV-index countries: sun-exposure behaviour in 7822 French
      adults.
AB  - BACKGROUND: Travel health information includes warning on sun exposure,
      particularly for fair-skinned individuals travelling to tropical countries.
      METHOD: A self-completed questionnaire on sun exposure behaviour was sent to the
      12,741 French adults enrolled in the SU.VI.MAX cohort. Among the 7822
      participants, 196 (110 women and 86 men) declared at least one visit to a high UV
      index country over the past year for more than 1 month, subsequently referred to
      as long-term travellers. The remaining 7626 participants (non-travellers)
      accounted for 4862 women and 2764 men. RESULTS: Women travellers declared more
      frequently skin exposure to the sun over the past year, practised tanning in high
      UV-index areas more than 2h daily, experienced intensive sun exposure than non
      travellers. Moreover, they asserted that basking in the sun is very important.
      Comparable results were found in men. The use of sun protection products was
      similar in travellers and non-travellers, but women tended to use sunscreen
      products more often, more regularly and with a higher sun protection factor (SPF)
      than men. CONCLUSIONS: Specific health education campaigns and pre-travel advice
      aiming to reduce sun exposure and to improve protective measures against
      ultraviolet (UV) radiation should be addressed to travellers to countries with
      high UV-index.

PMID- 17448946
TI  - Dengue fever and pregnancy - a review and comment.
AB  - BACKGROUND: The increasing incidence of dengue with the concomitant rise in
      travel during pregnancy makes it likely that a pregnant woman will plan travel to
      or present after travel to endemic areas. METHOD: Literature search and
      communication with researchers. RESULTS: Case reports of dengue during pregnancy,
      the peripartum period and neonatal dengue were found. There is little systematic
      research. CONCLUSIONS: Pregnancy appears not to increase the incidence or
      severity of dengue, but some case reports suggest that dengue may predispose to
      certain pregnancy complications. Transplacental infection occurs, but protective
      antibodies pass transplacentally and fetal effects may be minimal given
      sufficient immune response. In near-term disease, severe fetal or neonatal
      illness and death may occur. Such illness may also predispose the newborn to
      subsequent dengue hemorrhagic fever. Clinicians should be aware that presentation
      in either maternal or neonatal disease may be atypical and confound diagnosis.
      Women in late pregnancy should avoid travel to areas of ongoing disease, and
      those earlier in pregnancy should consider dengue a serious hazard. If travel is
      unavoidable, mosquito avoidance measures are mandated. If a woman acquires dengue
      fever while pregnant, conservative medical and obstetrical management are the
      treatments of choice. Further research is required.

PMID- 17448947
TI  - Problems in human rabies post-exposure prophylaxis management.
AB  - This is a prospective study of problems encountered with rabies-exposed patients
      in an animal bite clinic in a rabies endemic region. Five hundred successive
      patients were analyzed. The study focused mainly on issues that are not well
      covered in current WHO and US-CDC rabies manuals. Those dealing with
      immunoglobulin administration, managing severe and unusual injuries, logistic and
      financial issues headed the list. Animal bite patients often present challenging
      problems, which are not or inadequately addressed in official publications.
      Experience and good clinical judgment are essential in preventing human rabies.

PMID- 17448948
TI  - Q fever in an American tourist returned from Australia.
AB  - Q fever was diagnosed in a previously healthy man who had recently traveled to
      the East Coast of Australia. The patient experienced fever and headache
      accompanied by lymphopenia and elevated liver enzymes but not pneumonia. He had
      no known direct exposures to animals, exhibited IgM and IgG seroconversion to
      phase II antigen of Coxiella burnetii and IgM only to phase I antigen, and
      responded to doxycycline treatment. This case serves as a reminder to clinicians
      to consider Q fever in the differential diagnosis of acute febrile illness in
      travelers returning from endemic areas.

PMID- 17448949
TI  - Myiasis with Dermatobia hominis in a Sicilian traveller returning from Peru.
AB  - We report a case of a bot fly infestation of the scalp. A 45-year-old man after
      returning to Sicily noted a small white "worm" erupting from the upper lesion.
      Physical examination revealed a superficial furuncular lesion with central pores
      with sero-sanguineous discharge. The foreign body identified was diagnosed as the
      larva of the human bot fly, Dermatobia hominis.

PMID- 17448950
TI  - Case report: cutaneous myiasis caused by Dermatobia hominis, the human botfly.
AB  - Cutaneous myiasis caused by Dermatobia hominis, the human botfly, involves the
      infestation of human tissue with fly larvae, and is common in Central and South
      America. We report a case of a 57-year-old man with cutaneous myiasis imported
      into the US from Belize. The epidemiology, biological life cycle, clinical
      presentation, and various methods of larval extraction, including incision and
      drainage, are discussed.

PMID- 17448951
TI  - Take traveller's diarrhoea to heart.
AB  - Diarrhoea is a common health problem among travellers worldwide. We focus
      attention on the recognition of the postinfectious complications of traveller's
      diarrhoea. An English traveller, aged 43, attended a hospital in Benidorm (Spain)
      complaining of chest pain. A week previously, fever and severe diarrhoea were
      present. The electrocardiogram and cardiac enzymes were not normal. The
      coproculture yielded Campylobacter jejunii. Acute myocarditis can be an
      exceptional complication of gastroenteritis masquerading as acute myocardial
      infarction or leading to congestive heart failure.

PMID- 17448952
TI  - Risk assessment in haematopoietic stem cell transplantation.

PMID- 17448953
TI  - Risk assessment in haemotopoietic stem cell transplantation: disease and disease
      stage.
AB  - This chapter addresses the impact of the disease and disease status on the
      outcome of stem-cell transplantation. In consideration of the other topics
      addressed within this volume we have elected to focus on allogeneic rather than
      autologous transplantation. Furthermore we have not tried to be comprehensive and
      discuss the role of disease status in all conditions amenable to allografting,
      but rather to review the evidence that exists for selected haematological
      malignancies. Where possible we have made some clear recommendations, but where
      evidence is less clear we have indicated the ongoing controversies.

PMID- 17448955
TI  - Risk assessment in haematopoietic stem cell transplantation: minor
      histocompatibility antigens.
AB  - Minor histocompatibility (H) antigens are key molecules in graft-versus-host
      disease (GvHD) and the graft-versus-tumour effect after allogeneic stem-cell
      transplantation (SCT). Today, molecular typing methods allow an easy assessment
      of differences in minor H antigens between patient and donors, so that the GvHD
      risk in individual patients can be estimated. However, the large number of minor
      H antigens prevents matching for them to avoid GvHD. Interestingly, mismatching
      for minor H antigens might improve the outcome of allogeneic SCT. Some minor H
      antigens are expressed mainly by malignant cells and can therefore serve as
      excellent targets for cancer immunotherapy. Thus, mismatching for tumour
      expressed minor H antigens allows boosting of the curative effect of allogeneic
      SCT. Current research is elucidating the impact of e.g. donor immunization,
      immunodominance, or functional expression of minor H antigens on the extent of
      the GvH response.

PMID- 17448954
TI  - Risk assessment in haematopoietic stem cell transplantation: histocompatibility.
AB  - Consideration of potential donors for transplantation includes a rigorous
      assessment of the availability and HLA-match status of family members, and the
      identification of suitable unrelated donors when related donors are not
      available. Because HLA gene products provoke host-versus-graft and graft-versus
      host alloimmune responses, HLA matching serves a critical preventive role in
      lowering risks of graft failure and graft-versus-host disease (GVHD). At the same
      time, graft-versus-leukemia effects associated with HLA mismatching may provide
      an immunological means to lower the recurrence of post-transplant disease in high
      risk patients. The definition of a suitable allogeneic donor is ever changing,
      shaped not only by current typing technology for the known HLA genes but also by
      the specific transplant procedure. Increased safety of alternative donor
      hematopoietic cell transplantation (HCT) has been achieved in part through
      advances in the field of immunogenetics. Increased availability of HCT through
      the use of HLA-mismatched related and unrelated donors is feasible with a more
      complete understanding of permissible HLA mismatches and the role of NK-KIR genes
      in transplantation.

PMID- 17448956
TI  - Risk assessment in haematopoietic stem cell transplantation: pre-transplant
      patient and donor factors: non-HLA genetics.
AB  - Non-HLA genetics involving the study of single-nucleotide polymorphisms (SNPs)
      and microsatellites of cytokine and cytokine receptor genes, and as well as genes
      associated with response to infection and therapeutic drugs, are currently being
      studied for associations with diseases, including autoimmune disease, cancer and
      solid-organ transplant rejection. This chapter will summarize the potential role
      of non-HLA genetics in predicting outcome of haematopoietic stem-cell
      transplantation (HSCT) and how genotyping for non-HLA genes may give insight into
      the immunobiology of HSCT complications, including GvHD and infectious episodes.
      Future directions - including the role of pharmacogenomics, use of the research
      results for individualized medicine, and interpretation of data - will also be
      discussed.

PMID- 17448957
TI  - Risk assessment in haematopoietic stem cell transplantation: viral status.
AB  - Viral infections have been important complications in the transplant procedure
      from the early days of stem-cell transplantation, causing significant morbidity
      and mortality. It is important for the management of patients to assess the risk
      for viral infections that might develop after the stem-cell transplantation. This
      can be exemplified by cytomegalovirus (CMV) and other herpesviruses, but risk
      assessment is also important for other viral infections. The aim of this review
      is to describe current knowledge regarding recipient and donor serological status
      for viral infections.

PMID- 17448958
TI  - Risk assessment in haematopoietic stem cell transplantation: impact of donor
      recipient sex combination in allogeneic transplantation.
AB  - In allogeneic transplantation the donor-recipient sex combination plays a role in
      outcome. In large retrospective registry studies of several thousands of patients
      with aplastic anemia, chronic myelocytic leukemia (CML), acute myelocytic
      leukemia (AML), and multiple myeloma, chronic graft-versus-host disease (cGVHD)
      was more frequent and transplant-related mortality (TRM) higher in males with a
      female donor (F-->M) than in other donor-recipient sex combinations. Graft
      rejection was more frequent in females with a male donor (M-->F) in aplastic
      anemia, and a graft-versus-tumor effect (GVT) was documented as a reduced relapse
      rate in F-->M in CML, AML and multiple myeloma. The overall survival was
      adversely affected in F-->M in aplastic anemia, AML and CML and in M-->F in
      aplastic anemia. These results support the view that donor T cells specific for
      male minor histocompatiblity antigens encoded by Y-chromosome genes contribute to
      GVHD, graft rejection, GVT and survival in sex-mismatched transplants.

PMID- 17448959
TI  - Risk assessment in haematopoietic stem cell transplantation: the liver as a risk
      factor.
AB  - Patients with liver dysfunction have an increased risk of developing early and
      late complications after haematopoietic stem-cell transplantation (HSCT). That's
      why it is mandatory to evaluate liver status before transplantation in all cases.
      This evaluation should allow us to decide whether HSCT can be performed or
      whether we should adopt measures focused on preventing these complications. The
      evaluation of the liver in an HSCT candidate requires the collection of
      information by history-taking, physical examination, liver-function tests and,
      occasionally, imaging tests and liver biopsy. Additionally, as infection by
      hepatitis B or C viruses represents the most relevant cause of hepatic
      dysfunction after HSCT, the serological status of the patient should be carefully
      evaluated. This chapter tries to analyse and systematise the most important
      aspects in the patient's evaluation. Finally, as some liver dysfunctions in the
      stem-cell donor can have a negative impact for the donor during the harvest
      and/or for the recipient during HSCT, the methodology to evaluate the donors will
      also be analysed.

PMID- 17448960
TI  - Cardiac assessment of patients for haematopoietic stem cell transplantation.
AB  - The expanding role of haematopoietic stem-cell transplantation (HSCT) renders the
      previous policy of avoiding transplantation in high-risk cardiac patients
      obsolete. Patients with amyloid, autoimmune conditions, sickle-cell disease, or
      thalassaemia, and patients over the age of 60 years are increasingly being
      offered HSCT. It is evident that the policy of avoiding transplantation in
      patients with impaired systolic function fails to identify all high-risk patients
      in such groups, and will deprive some patients of the benefits of HSCT
      unnecessarily. The development of an appropriate algorithm for cardiac pre
      assessment and peri-transplant management is hampered by an inadequate
      understanding of the predictive value of various tests of cardiovascular
      function, the rapid evolution of advanced management strategies for cardiac
      dysfunction, and the development of non-cardiotoxic conditioning regimens. To
      meet this need we propose that an algorithm based on evidence from other clinical
      situations - already been found to be successful in the management of HSCT in
      patients with systemic sclerosis - should be used uniformly, and registry studies
      should be undertaken to distinguish those aspects of the algorithm that
      positively help to expand the remit of HSCT from those that add little of value.

PMID- 17448961
TI  - Risk assessment in haematopoietic stem cell transplantation: stem cell source.
AB  - Bone marrow (BM) has been used for many years as the unique source of progenitor
      cells for allogeneic transplantation. However, two other sources of progenitor
      cells, peripheral blood (PB) and umbilical cord (UC), are being increasingly
      used. The type of graft is one of the most important factors in determining the
      speed and robustness of the reconstitution after the transplant of monocytes, T
      lymphocytes, B lymphocytes, NK cells, and dendritic cells. This fact is of
      especial relevance since the most important reactions after allogeneic
      transplants - e.g. graft-versus-host disease (GVHD), graft-versus-leukaemia
      effect (GvL), achievement of full donor chimerism, and fight against infections -
      are strongly influenced by a rapid and robust reconstitution of these cells. For
      this reason, the choice of the type of graft for allogeneic transplantation will
      influence the clinical outcome.

PMID- 17448962
TI  - Risk assessment in haematopoietic stem cell transplantation: GvHD prevention and
      treatment.
AB  - Graft-versus-host disease (GvHD) is the major cause of transplant-related
      mortality and morbidity. As it is closely related to the major therapeutic
      principle, graft-versus-leukaemia (GvL) effect, risk assessment has to balance
      both risks depending on the pre-transplant status. This is clearly demonstrated
      when comparing the two major strategies for prevention of GvHD. While the
      majority of approaches aiming at T-cell depletion show efficacy in reducing acute
      and chronic GvHD and transplant-related mortality, T-cell depletion also affects
      graft-versus-leukaemia effects and thus results in a higher relapse rate. Thus,
      standard prophylaxis relying on calcineurin inhibitors frequently results in at
      least equivalent or even superior long-term disease-free survival, and the risk
      of relapse has to be considered when selecting regimens for prevention of GvHD.
      In addition to this general dilemma, drug-specific side-effects and risks have to
      be considered when selecting regimens for GvHD prevention and treatment.

PMID- 17448963
TI  - Risk assessment in haematopoietic stem cell transplantation: conditioning.
AB  - After the introduction of cyclophosphamide and total body irradiation in the
      1970s, a variety of conditioning regimens has been developed. However, none has
      proven to be superior. Fractionation of the irradiation results in less toxic
      side-effects, but the total dose has to be increased to obtain similar
      immunosuppressive effects. Data from randomized trials indicate that among
      patients with myeloid leukaemia, busulfan in combination with cyclophosphamide
      results in similar outcome, while a regimen containing total body irradiation is
      probably still the best for patients with acute lymphoblastic leukaemia. Busulfan
      treatment can be optimized by targeted steady-state concentration or with the use
      of intravenous preparations. Intensified regimens decrease the relapse incidence,
      but because of a higher mortality from transplant-related causes survival is
      unchanged. Reduced-intensity conditioning can reduce transplant-related mortality
      and offer otherwise ineligible patients a potentially curative treatment. Long
      term results are unknown.

PMID- 17448964
TI  - Disease relapse after haematopoietic stem cell transplantation: risk factors and
      treatment.
AB  - Disease relapse is the commonest cause of treatment failure after allogeneic
      haematopoietic stem-cell transplantation. Adoptive immunotherapy based on donor
      lymphocyte infusions (DLI) has a prominent role in the management of disease
      recurrence. Although the highest remission rates are achieved in chronic myeloid
      leukaemia (CML), encouraging results have also been reported in chronic
      lymphoproliferative disorders. However, the experience of DLI in CML is not
      necessarily applicable to the management of lymphoproliferative diseases because
      of the heterogeneity of the conditioning regimens used in chronic lymphoid
      malignancies. We will review the role of DLI for different disease types in the
      context of conventional and reduced-intensity conditioning regimens. The factors
      influencing response and graft-versus-host disease as well as the optimal cell
      dose will be discussed. Finally, we will describe the main avenues currently
      being explored to improve the selectivity and efficacy of DLI.

PMID- 17448965
TI  - Immune reconstitution following hematopoietic stem-cell transplantation.
AB  - Hematopoietic stem-cell transplantation is associated with a profound immune
      deficiency manifested as an increased propensity to develop infections and
      probably also malignancies. Innate immunity, including epithelial barriers and
      phagocytes, typically recovers within weeks after grafting, and B-cell counts and
      CD8 T-cell counts recover within months. CD4 T-cell counts are low for years, and
      their recovery is particularly slow in older patients with poor thymic function.
      Therapies to improve immune function include vaccinations, immunoglobulins for
      recurrent infections, cytokines, and antigen-specific donor lymphocyte infusions.

PMID- 17448966
TI  - Autoimmunity following haematopoietic stem-cell transplantation.
AB  - Autoimmunity after stem-cell transplantation has been observed over decades.
      Evidence comes from single case reports or small series. Autoimmune phenomena are
      known in both the autologous and the allogeneic settings, irrespective of the
      graft source. Most publications deal with autoantibody production after
      transplantation; more rarely, the appearance of the associated autoimmune disease
      is reported. Autoimmune thyroid disease and autoimmune cytopenias are most often
      described. Homeostatic expansion after transplantation-induced lymphopenia is
      thought to be a trigger for loss of self-tolerance and proliferation of
      autoreactive T-cells in these patients. With allogeneic haematopoietic stem-cell
      transplantation, adoptive transfer of autoimmune disease has been shown, raising
      the issue of graft quality. Many of the clinical and laboratory features of graft
      versus-host disease (GvHD), especially in its chronic form, resemble those of
      autoimmune diseases, and the pathophysiological mechanisms are similar.
      Prospective data for a better understanding of autoimmunity and 'altered'
      immunity after stem-cell transplantation are needed.

PMID- 17448967
TI  - An alternative model of cancer cell growth and metastasis.
AB  - I propose an alternative model of cancer in which metastasis need not all arise
      out of spread from the "original" tumour. The model assumes that cancer cells
      arise from stem cells that best grow in the organ of their differentiation. When
      the internal milieu allows it they also grow at other sites as well, thus
      complementing the conventional (spreading) metastatic process. Several phenomena
      in the natural history of cancer, especially breast cancer, that challenge the
      conventional model, fit well after inclusion of the new model. These are (a) a
      very modest benefit of screening (b) frequent sparing of lungs from haematogenous
      metastasis (c) presence of occult cancers in autopsy studies (d) only a modest
      effect of local treatment (e) relative ineffectiveness of high-dose chemotherapy
      (f) constant time between surgery and peak of hazard of relapse irrespective of
      stage of the tumour. All these phenomena are much easier to explain when one
      rejects the dogma that all metastasis arise only from the primary tumour. This
      paper is aimed only to suggest an alternative perspective of natural history of
      solid tumours--to stimulate research on the complex internal milieu that allows
      cancer cells to develop in new light.

PMID- 17448968
TI  - Patients' view on intraoperative diagnosis of sentinel nodes in breast cancer: is
      it an automatic choice?
AB  - Intraoperative detection of sentinel node metastases in breast cancer enables
      immediate axillary lymph node dissection. This approach, however, introduces
      uncertainty for patients as to the extent of surgery. Waking to find a surgical
      drain implies more extensive surgery and worse prognosis disease. False negative
      diagnoses may cause disappointment. AIM: To evaluate patients' views and
      preferences on intraoperative diagnosis of sentinel nodes in breast cancer.
      METHODS: Questionnaire based survey of 100 patients who had previously undergone
      sentinel node biopsy with intraoperative diagnosis using touch imprint cytology
      (TIC). Patients were encouraged to add free text comments. RESULTS: Sixty-four
      patients responded to the questionnaire. Patients rated the information provided
      and their understanding of the procedure highly. Fifty-nine percent of
      respondents overestimated the sensitivity of TIC. Ninety-five percent of patients
      would choose to undergo intraoperative diagnosis in future if required. Five
      percent of patients would choose not to undergo intraoperative diagnosis, citing
      the resultant uncertainty, disappointment on waking and needing time to come in
      terms with the diagnosis of metastases as reasons. CONCLUSION: Given the choice,
      most patients would choose intraoperative diagnosis, though a minority would
      explicitly not, due to the adverse psychological effect thereof. Despite a good
      understanding of the procedure, the majority of patients overestimate the
      sensitivity of intraoperative diagnosis of sentinel nodes, which may heighten
      disappointment when a false negative diagnosis occurs. Intraoperative diagnosis
      should not be the automatic choice and patients should be actively involved in
      this decision making process.

PMID- 17448969
TI  - How to teach the teacher to teach the TUR-B.
AB  - OBJECTIVES: We report on our training program in teaching TUR of bladder tumours
      to seven trainees in two distinct periods. We analysed their problems and those
      from teachers and we present our solutions. MATERIAL AND METHODS: Between April
      2000 and April 2004 seven trainees performed 842 TUR of bladder tumours. In a
      prospective study we assessed intraoperative and immediate postoperative
      complications of the procedures and analysed their causes. RESULTS: In 48 months
      842 teaching TUR were performed. Six hundred and thirty-one patients (75%) were
      male and 211 (25%) were female. The average age was 63.4 years (range 32-92) in
      the males and 67.3 years (range 48-91) in the females. There were complications
      in 81 cases (6.1%). The most common complication was bleeding. It occurred in 47
      cases (3.5%). The second most common complication was bladder perforation. It
      occurred in 18 cases (1.3%). All but one of the patients who experienced a
      bladder perforation were male and all but one of the perforations were
      extraperitoneal and could be managed in a conservative fashion. CONCLUSION: The
      standard of TUR is video-controlled resection. The procedure has to be
      standardised following a protocol to avoid incomplete resections. The trainee
      should start his TUR experience on middle sized prostates and once the first
      skills have been acquired he can start to resect bladder tumours in so called
      "safe areas". The last step is then complete autonomy. To bring a trainee to this
      goal remains a challenge for each trainer.

PMID- 17448970
TI  - Subserosal appendicular stripping.
AB  - Appendicectomy in patients with recurrent appendicitis can be difficult due to an
      adherent and inflamed appendix. We describe the technique and results of
      subserosal appendicular stripping (SAA). Over a four-year period, 49 patients who
      were diagnosed with recurrent appendicitis required SAA. They had prior admission
      for acute appendicitis which resolved with antibiotic treatment. Persistent
      symptoms necessitated surgery. SAA was necessary in these patients due to an
      inflamed, adherent appendix with extensive serosal adhesions. The appendix was
      delivered out from the serosa following retrograde ligation of the appendicular
      base. The adherent serosa was left intact. Average patient age was 23 years. All
      had persistent symptoms for more than one week with a history of one or more
      previous attacks. No surgical complications were observed except transient
      serosal bleeding in the first case managed by gentle diathermy. We advocate SAA
      as a modification of appendicectomy in patients with recurrent appendicitis where
      the appendix is inflamed and adherent.

PMID- 17448972
TI  - Epidemiologic features, seasonal variations and false positive rate of acute
      appendicitis in Shahr-e-Rey, Tehran.
AB  - INTRODUCTION: Appendicitis is the most common acute surgical condition of the
      abdomen. Age, sex and seasonal variations have been observed in many studies. To
      describe and find the possible differences in the epidemiology of acute
      appendicitis in Shahr-e-Rey, we carried out a retrospective study of all patients
      with acute appendicitis admitted to Shohadaay-e Haftom-e Tir hospital as it is
      the only hospital in this restricted part of Tehran. METHODS: Using hospital
      discharge abstract of patients who were admitted with the diagnosis of acute
      appendicitis from summer 1996 to spring 2004, we studied the demographic
      features, particularly age and sex, date of admission and final diagnosis of
      these patients. RESULTS: During the observation period, 1093 cases were admitted
      with the diagnosis of acute appendicitis. Of these, 74.4% were males and 6.1%
      were not actually an acute appendicitis. The age-specific incidence of acute
      appendicitis has different patterns in male and female. The incidence was highest
      in males aged 20-29 years whereas in females the highest incidence was observed
      in 10-19 years age group. A significant seasonal effect was also observed, with
      the rate of acute appendicitis higher in the summer months (p<0.006). The rate of
      false positive diagnosis was highest in the patients aged 0-9 years (p<0.0001).
      Of those correctly diagnosed, 85.5% had uncomplicated acute appendicitis; 8.3%
      had perforation; and others (6.2%) had acute appendicitis complicated with other
      situations. CONCLUSION: Appendicitis is more common in males, in those aged 20-29
      years, and during the summer months. The age-specific incidence and sex ratio of
      acute appendicitis give the impression that epidemiologic features of acute
      appendicitis are different with worldwide data. However, the seasonal variation
      and false positive rate of acute appendicitis are in a good agreement with other
      studies.

PMID- 17448971
TI  - Preoperative haematinics and transfusion protocol reduce the need for transfusion
      after total knee replacement.
AB  - BACKGROUND: Unilateral total knee replacement (TKR) can result in a substantial
      blood loss and 30-50% of these patients receive allogeneic blood transfusion
      (ABT), this transfusion rate may be even higher among anaemic patients. PATIENTS
      AND METHODS: We assessed the requirements for ABT in 156 consecutive patients
      undergoing surgery for primary TKR, who received iron ferrous sulphate (256
      mg/day; 80 mg of Fe(2+)), vitamin C (1000 mg/day) and folic acid (5mg/day) during
      the 30-45 days preceding surgery, and who were transfused if Hb <80 g/L and/or
      clinical signs/symptoms of acute anaemia/hypoxemia (Group 2). A previous series
      of 156 TKR patients serves as a control group (Group 1). RESULTS: Compared to
      those in Group 1, patients in Group 2 presented a lower transfusion rate (5.8%
      vs. 32%, for Group 2 and Group 1, respectively; p<0.01), and a lower transfusion
      index (1.78+/-0.44 vs. 2.22+/-0.65 units per transfused patient, respectively;
      p<0.05). After patient's stratification according to a preoperative Hb above or
      below 130 g/L, the differences in transfusion rate remained significant, although
      19% of patients from Group 2 still needed ABT if their preoperative Hb <130 g/L.
      CONCLUSION: This protocol seems to be effective for avoiding ABT in non-anaemic
      TKR patients, whereas for anaemic patients another blood saving strategy, such us
      preoperative erythropoietin administration or postoperative blood salvage, should
      be added to further increase its effectiveness.

PMID- 17448973
TI  - The role of [18F]fluoride positron emission tomography in the early detection of
      aseptic loosening of total knee arthroplasty.
AB  - Total knee arthroplasty is successful in the treatment of degenerative, arthritic
      or injured joints. But the most important long term complication seems to be
      aseptic loosening. An inflammatory process at the bone/cement or bone/prosthesis
      interface leads to a severe osteolysis. Although early diagnosis is very
      important the standard techniques often fail. [(18)F]Fluoride ion positron
      emission tomography (F-PET) is an appropriate tracer paired with a modern method
      for the evaluation of increased bone metabolism at the bone/prosthesis interface.
      In this preliminary study we describe for the first time the value of F-PET in
      the early diagnosis of aseptic loosening. We studied 14 painful knee
      arthoplasties. In 6 cases the definite diagnosis was determined by surgical
      procedure, for 8 cases a long clinical follow-up of the least 6 months after the
      onset of symptoms led to the diagnosis. The F-PET scans were obtained by with an
      ECAT EXACT HR+ scanner with and without attenuation correction in the two-and
      three-dimensional mode. An intermediate or high uptake along the bone/prosthesis
      or bone/cement interface including either the tibial stem or the half of the
      femoral component was suspected to be aseptic loose. The result were compared
      with plain radiographs. We found a sensitivity of 100%, a specificity of 56% and
      an accuracy of 71%. No false negative results were detected, in 4 patients one
      component as false positive. The sensitivity, specificity and accuracy for the
      plain radiograph of the same patients were 43%, 86% and 64%, respectively. In
      conclusion PET seems to be a promising new method in the early diagnosis of
      painful TKA because of its excellent spatial solution. In combination with the
      bone seeking tracer [(18) F]fluoride, PET allows the detection of aseptic
      loosening and the differentiation to the simple synovitis. Our preliminary
      results suggest that F-PET could be a useful tool although we examined a small
      group of patients.

PMID- 17448974
TI  - The diagnostic accuracy of clinical examination in hand lacerations.
AB  - INTRODUCTION: Hand injuries account for a significant proportion of emergency
      department attendance. We investigated the diagnostic accuracy of clinical
      examination in patients with simple hand lacerations undergoing surgical
      exploration at our unit. METHODS: One hundred and sixty-five consecutive patients
      were identified as undergoing exploration of the hand. Case notes of these
      patients were reviewed. The clinical findings, made by emergency department
      doctors (ED) and hand surgeons (HS), were compared with the operative findings.
      RESULTS: A total of 101 patients were included following exclusion criteria. Both
      ED and HS correctly identified 68.2% of flexor tendon injuries. Overall, the ED
      diagnosed accurately significantly fewer extensor tendon injuries (ED 65.6% vs HS
      75.0%, p<0.001). Similarly, HS diagnosed nerve injuries more accurately than ED
      (ED 54.5% vs HS 78.8%, p<0.005). DISCUSSION: Clinical examination forms an
      important part of the patient assessment, provides the surgeon with an idea of
      which structures are potentially injured, and its value should never be
      underestimated. Formal exploration, however, should be undertaken since both ED
      and HS missed about 30% injuries.

PMID- 17448975
TI  - Comparing vein with collagen impregnated woven polyester prosthesis in above-knee
      femoropopliteal bypass grafting.
AB  - OBJECTIVE: Despite many clinical studies, there is still uncertainty as to
      whether venous material is superior to prosthetic materials for femoropopliteal
      reconstruction proximal to the knee joint. A prospectively randomized clinical
      trial was designed to evaluate the effectiveness of reversed saphenous vein in
      comparison with that of collagen impregnated woven polyester prosthesis in above
      knee arterial reconstruction. METHODS: In a 3-year period, 103 above-knee
      femoropopliteal bypass graft operations were performed and followed in 85
      patients (52 male, 33 female). The indication for operation was severe
      claudication in 74 cases, rest pain in 7 cases, and ulceration in 4 cases. For
      the bypass graft, a reversed saphenous vein was used in each of 51 cases, and a
      collagen impregnated woven polyester prosthesis was used in each of 52 cases.
      Preoperative risk factors were diabetes (24%), a history of myocardial infarction
      (23%), and current status with respect to smoking (74%). There was no hospital
      mortality; 5% of patients had minor postoperative complications. RESULTS: After 2
      years of follow-up, the primary patency was 81% for saphenous vein and 67% for
      collagen impregnated woven polyester prosthesis (P=0.065); the secondary patency
      was 81% for saphenous vein and 77% for collagen impregnated woven polyester
      prosthesis (P=0.298). During this follow-up period of 2 years, we found no
      statistically significant difference in primary and secondary patency between
      saphenous vein and collagen impregnated woven polyester prosthesis. We found no
      predictive factor for the occlusion of either bypass graft. CONCLUSION: The use
      of collagen impregnated woven polyester prosthesis above the knee is a reasonable
      alternative in femoropopliteal bypass grafting that is associated with acceptable
      short-term patency rates.

PMID- 17448976
TI  - Optimal dosing of bemiparin as prophylaxis against venous thromboembolism in
      surgery for cancer: an audit of practice.
AB  - AIMS: Low-molecular-weight heparins are drugs of first choice for
      thromboprophylaxis in cancer surgery. We sought to determine the optimal use of
      bemiparin in cancer surgery in standard clinical practice. PATIENTS AND METHODS:
      A retrospective, multicentre audit on the use of bemiparin in patients undergoing
      cancer surgery and given prophylaxis with bemiparin was undertaken. Surgeons'
      assessment of venous thromboembolic (VTE) risk (moderate or high) was compared to
      the criteria of current Consensus Guidelines for VTE management. We assessed the
      incidence of documented symptomatic VTE, bleeding events, thrombocytopenia,
      deaths and total events related to VTE or bemiparin prophylaxis (i.e. bleeding,
      thrombocytopenia). The potential economic impact of postoperative vs.
      preoperative bemiparin was also analysed. RESULTS: Clinical records from 197
      patients from 5 Spanish centres were checked. Prophylaxis was started
      postoperatively in 45 patients (22.8%). According to the surgeons' criteria, 73
      (37.1%) patients were at high VTE risk and received bemiparin 3500 IU/d. However,
      according to the criteria of current Guidelines, 189 (95.9%) patients were at
      high risk of VTE (heterogeneity P-value<0.0001). Three (1.5%) patients, all of
      them receiving bemiparin 2500 IU/d, developed a symptomatic confirmed VTE. There
      were 4 major and 5 minor bleeding events during bemiparin prophylaxis. A lower
      incidence of bleeding (2.2% vs. 5.3%; P=0.48) and total events (2.2% vs. 9.9%;
      P=0.11) was seen with bemiparin started postoperatively as compared to
      preoperative bemiparin. Bleeding rates did not significantly differ between
      patients given low or high bemiparin prophylactic doses (4.0% vs. 5.5%; P=0.72).
      Two patients died due to cardio-respiratory failure and sepsis, respectively.
      Postoperative bemiparin provided net cost savings of 909 euro per patient
      compared to preoperative start of prophylaxis due to shorter hospital stays (9
      vs. 11 days) and lower incidence of complications in the postoperative bemiparin
      group. CONCLUSIONS: Many cancer patients are still poorly assessed for risk of
      VTE. Bemiparin 3500 IU/d is associated with a lower incidence of VTE without
      significant increase in complications as compared with bemiparin 2500 IU/d.
      Postoperative bemiparin prophylaxis seems to be as effective and safer than
      preoperative start of prophylaxis. Further prospective clinical studies are
      needed to fully address this issue.

PMID- 17448977
TI  - Follow-up of patients with colorectal cancer: the evidence is in favour but we
      are still in need of a protocol.
AB  - The prevalence of colorectal cancer is high in the western world and follow-up
      after treatment of the primary tumour is claimed to consume resources that could
      be used in improving screening and early diagnosis. Although some patients with
      recurrent disease can be treated successfully there has been a debate on whether
      an overall improvement in survival is achieved by follow-up. There is no
      agreement on a follow-up protocol of investigations. A review via a Medline
      search of all published studies and reports on the issue of follow-up of
      colorectal cancer dated from 1975-2006. We examined retrospective and prospective
      studies, randomised controlled trials, and meta-analyses attempting to identify
      the optimum follow-up protocol. There is widespread diversity of follow-up
      policies for colorectal cancer. Follow-up of colorectal cancer does not have a
      negative impact on Quality of life. There is no evidence that annual colonoscopy
      provides any survival advantage. It has been shown that intensive follow-up with
      frequent carcinoembryonic antigen measurement has a survival advantage and is
      cost-efficient. Similar evidence seems to be gathering about liver imaging with
      CT scan although it is less conclusive.

PMID- 17448978
TI  - Nobel Prizes for surgeons: In recognition of the surgical healing strategy.
AB  - Theodor Kocher (1909), Alexis Carrel (1912), Antonio Egas Moniz (1949) and Joseph
      E. Murray (1990) received Nobel Prizes for their accomplishments in the field of
      surgery. This essay puts these achievements in the context of the history of
      surgery, in particular its recognition of a field of modern medicine. It
      characterizes the view of the body that is associated with modern surgery and the
      specific surgical healing strategy that the Nobel Prizes acknowledged.

PMID- 17448979
TI  - Drains post-breast reconstruction surgery: a necessity difficult to contain.

PMID- 17448980
TI  - Green genes-comparative genomics of the green branch of life.
AB  - As more plant genome sequences become available, researchers are increasingly
      using comparative genomics to address some of the major questions in plant
      biology. Such questions include the evolution of photosynthesis and
      multicellularity, the developmental genetic changes responsible for alterations
      in body plan, and the origin of important plant innovations such as roots,
      leaves, and vascular tissue.

PMID- 17448981
TI  - A new partner for the international knockout mouse consortium.

PMID- 17448982
TI  - A single origin of the central nervous system?
AB  - As Denes et al. (2007) reveal in this issue, the expression profile and roles of
      genes that pattern the nervous system in embryos of chordates and annelids are
      surprisingly similar. This extraordinary conservation suggests that the
      patterning mechanism has been inherited largely unchanged from the bilaterian
      common ancestor and that the central nervous system, although dorsal in fish and
      ventral in worms, is an ancient characteristic of animals.

PMID- 17448983
TI  - Zfx: at the crossroads of survival and self-renewal.
AB  - As the molecular mechanisms that govern stem cell fate are beginning to be
      unraveled, Galan-Caridad et al. (2007) report in this issue of Cell a common role
      for the transcription factor Zfx in the self-renewal/maintenance of both
      embryonic stem cells and hematopoietic stem cells. Their work suggests that a
      regulator of self-renewal can be shared between two different cell types.

PMID- 17448984
TI  - Ephs and ephrins keep pancreatic Beta cells connected.
AB  - How insulin-secreting beta cells of the pancreas communicate with each other is
      largely unknown. In this issue of Cell, Konstantinova et al. (2007) show that the
      signaling proteins EphA and ephrin-A modulate insulin secretion, providing fresh
      insights into the functional significance of the clustering of beta cells, which
      occurs in islets.

PMID- 17448985
TI  - Targeting the sticky fingers of HIV-1.
AB  - Although human blood plasma contains molecules that inhibit the activity of HIV
      1, their identity is largely unknown. Munch et al. (2007) now identify a peptide
      corresponding to a portion of alpha1-antitrypsin that potently inhibits entry of
      HIV-1 into host cells by binding to a hydrophobic segment of the viral envelope
      glycoprotein gp41.

PMID- 17448986
TI  - Molecules to remember.
AB  - "Working memory" is used for the transient storage of information in the brain.
      In this issue of Cell, Wang et al. (2007) now reveal how a series of molecular
      events involving alpha2A-adrenoceptors and a class of ion channels gated by cAMP
      tune the responses of neural circuits that function in working memory in mammals.

PMID- 17448987
TI  - miR-1-2 gets to the heart of the matter.
AB  - Although many microRNAs (miRNAs) and their targets have been identified, the
      importance of miRNAs in vivo is still unclear. In this issue, Zhao et al. (2007)
      generate mice deficient in a cardiac-specific miRNA, miR-1-2, and reveal that
      this microRNA plays a crucial role in heart development and physiology.

PMID- 17448988
TI  - The hormonal control of food intake.
AB  - Numerous circulating peptides and steroids produced in the body influence
      appetite through their actions on the hypothalamus, the brain stem, and the
      autonomic nervous system. These hormones come from three major sites-fat cells,
      the gastrointestinal tract, and the pancreas. In this Review we provide a
      synthesis of recent evidence concerning the actions of these hormones on food
      intake.

PMID- 17448989
TI  - Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp41
      fusion peptide.
AB  - A variety of molecules in human blood have been implicated in the inhibition of
      HIV-1. However, it remained elusive which circulating natural compounds are most
      effective in controlling viral replication in vivo. To identify natural HIV-1
      inhibitors we screened a comprehensive peptide library generated from human
      hemofiltrate. The most potent fraction contained a 20-residue peptide, designated
      VIRUS-INHIBITORY PEPTIDE (VIRIP), corresponding to the C-proximal region of
      alpha1-antitrypsin, the most abundant circulating serine protease inhibitor. We
      found that VIRIP inhibits a wide variety of HIV-1 strains including those
      resistant to current antiretroviral drugs. Further analysis demonstrated that
      VIRIP blocks HIV-1 entry by interacting with the gp41 fusion peptide and showed
      that a few amino acid changes increase its antiretroviral potency by two orders
      of magnitude. Thus, as a highly specific natural inhibitor of the HIV-1 gp41
      fusion peptide, VIRIP may lead to the development of another class of
      antiretroviral drugs.

PMID- 17448990
TI  - Molecular architecture of annelid nerve cord supports common origin of nervous
      system centralization in bilateria.
AB  - To elucidate the evolutionary origin of nervous system centralization, we
      investigated the molecular architecture of the trunk nervous system in the
      annelid Platynereis dumerilii. Annelids belong to Bilateria, an evolutionary
      lineage of bilateral animals that also includes vertebrates and insects.
      Comparing nervous system development in annelids to that of other bilaterians
      could provide valuable information about the common ancestor of all Bilateria. We
      find that the Platynereis neuroectoderm is subdivided into longitudinal
      progenitor domains by partially overlapping expression regions of nk and pax
      genes. These domains match corresponding domains in the vertebrate neural tube
      and give rise to conserved neural cell types. As in vertebrates, neural
      patterning genes are sensitive to Bmp signaling. Our data indicate that this
      mediolateral architecture was present in the last common bilaterian ancestor and
      thus support a common origin of nervous system centralization in Bilateria.

PMID- 17448991
TI  - The crystal structure of yeast fatty acid synthase, a cellular machine with eight
      active sites working together.
AB  - In yeast, the whole metabolic pathway for making 16- and 18-carbon fatty acids is
      carried out by fatty acid synthase, a 2.6 megadalton molecular-weight
      macromolecular assembly containing six copies of all eight catalytic centers. We
      have determined its crystal structure, which illuminates how this enzyme is
      initially activated and then carries out multiple steps of synthesis in each of
      six sterically isolated reaction chambers. Six of the catalytic sites are in the
      wall of the assembly facing an acyl carrier protein (ACP) bound to the ketoacyl
      synthase domain. Two-dimensional diffusion of substrates to the catalytic sites
      may be achieved by the electrostatically negative ACP swinging to each of the six
      electrostatically positive catalytic sites. The phosphopantetheinyl transferase
      domain lies outside the shell of the assembly, inaccessible to ACP that lies
      inside, suggesting that the attachment of the pantetheine arm to ACP must occur
      before complete assembly of the complex.

PMID- 17448992
TI  - Modulation of cellular disulfide-bond formation and the ER redox environment by
      feedback regulation of Ero1.
AB  - Introduction of disulfide bonds into proteins entering the secretory pathway is
      catalyzed by Ero1p, which generates disulfide bonds de novo, and Pdi1p, which
      transfers disulfides to substrate proteins. A sufficiently oxidizing environment
      must be maintained in the endoplasmic reticulum (ER) to allow for disulfide
      formation, but a pool of reduced thiols is needed for isomerization of
      incorrectly paired disulfides. We have found that hyperoxidation of the ER is
      prevented by attenuation of Ero1p activity through noncatalytic cysteine pairs.
      Deregulated Ero1p mutants lacking certain cysteines show increased enzyme
      activity, a decreased lag phase in kinetic assays, and growth defects in vivo. We
      hypothesize that noncatalytic cysteine pairs in Ero1p sense the level of
      potential substrates in the ER and correspondingly modulate Ero1p activity as
      part of a homeostatic regulatory system governing the thiol-disulfide balance in
      the ER.

PMID- 17448994
TI  - EphA-Ephrin-A-mediated beta cell communication regulates insulin secretion from
      pancreatic islets.
AB  - In vertebrates, beta cells are aggregated in the form of pancreatic islets.
      Within these islets, communication between beta cells inhibits basal insulin
      secretion and enhances glucose-stimulated insulin secretion, thus contributing to
      glucose homeostasis during fasting and feeding. In the search for the underlying
      molecular mechanism, we have discovered that beta cells communicate via ephrin-As
      and EphAs. We provide evidence that ephrin-A5 is required for glucose-stimulated
      insulin secretion. We further show that EphA-ephrin-A-mediated beta cell
      communication is bidirectional: EphA forward signaling inhibits insulin
      secretion, whereas ephrin-A reverse signaling stimulates insulin secretion. EphA
      forward signaling is downregulated in response to glucose, which indicates that,
      under basal conditions, beta cells use EphA forward signaling to suppress insulin
      secretion and that, under stimulatory conditions, they shift to ephrin-A reverse
      signaling to enhance insulin secretion. Thus, we explain how beta cell
      communication in pancreatic islets conversely affects basal and glucose
      stimulated insulin secretion to improve glucose homeostasis.

PMID- 17448993
TI  - Zfx controls the self-renewal of embryonic and hematopoietic stem cells.
AB  - Stem cells (SC) exhibit a unique capacity for self-renewal in an undifferentiated
      state. It is unclear whether the self-renewal of pluripotent embryonic SC (ESC)
      and of tissue-specific adult SC such as hematopoietic SC (HSC) is controlled by
      common mechanisms. The deletion of transcription factor Zfx impaired the self
      renewal but not the differentiation capacity of murine ESC; conversely, Zfx
      overexpression facilitated ESC self-renewal by opposing differentiation.
      Furthermore, Zfx deletion abolished the maintenance of adult HSC but did not
      affect erythromyeloid progenitors or fetal HSC. Zfx-deficient ESC and HSC showed
      increased apoptosis and SC-specific upregulation of stress-inducible genes. Zfx
      directly activated common target genes in ESC and HSC, as well as ESC-specific
      target genes including ESC self-renewal regulators Tbx3 and Tcl1. These studies
      identify Zfx as a shared transcriptional regulator of ESC and HSC, suggesting a
      common genetic basis of self-renewal in embryonic and adult SC.

PMID- 17448995
TI  - The neuronal channel NALCN contributes resting sodium permeability and is
      required for normal respiratory rhythm.
AB  - Sodium plays a key role in determining the basal excitability of the nervous
      systems through the resting "leak" Na(+) permeabilities, but the molecular
      identities of the TTX- and Cs(+)-resistant Na(+) leak conductance are totally
      unknown. Here we show that this conductance is formed by the protein NALCN, a
      substantially uncharacterized member of the sodium/calcium channel family. Unlike
      any of the other 20 family members, NALCN forms a voltage-independent,
      nonselective cation channel. NALCN mutant mice have a severely disrupted
      respiratory rhythm and die within 24 hours of birth. Brain stem-spinal cord
      recordings reveal reduced neuronal firing. The TTX- and Cs(+)-resistant
      background Na(+) leak current is absent in the mutant hippocampal neurons. The
      resting membrane potentials of the mutant neurons are relatively insensitive to
      changes in extracellular Na(+) concentration. Thus, NALCN, a nonselective cation
      channel, forms the background Na(+) leak conductance and controls neuronal
      excitability.

PMID- 17448996
TI  - Long-range Ca2+ signaling from growth cone to soma mediates reversal of neuronal
      migration induced by slit-2.
AB  - Neuronal migration and growth-cone extension are both guided by extracellular
      factors in the developing brain, but whether these two forms of guidance are
      mechanistically linked is unclear. Application of a Slit-2 gradient in front of
      the leading process of cultured cerebellar granule cells led to the collapse of
      the growth cone and the reversal of neuronal migration, an event preceded by a
      propagating Ca(2+) wave from the growth cone to the soma. The Ca(2+) wave was
      required for the Slit-2 effect and was sufficient by itself to induce the
      reversal of migration. The Slit-2-induced reversal of migration required active
      RhoA, which was accumulated at the front of the migrating neuron, and this
      polarized RhoA distribution was reversed during the migration reversal induced by
      either the Slit-2 gradient or the Ca(2+) wave. Thus, long-range Ca(2+) signaling
      coordinates the Slit-2-induced changes in motility at two distant parts of
      migrating neurons by regulating RhoA distribution.

PMID- 17448997
TI  - Alpha2A-adrenoceptors strengthen working memory networks by inhibiting cAMP-HCN
      channel signaling in prefrontal cortex.
AB  - Spatial working memory (WM; i.e., "scratchpad" memory) is constantly updated to
      guide behavior based on representational knowledge of spatial position. It is
      maintained by spatially tuned, recurrent excitation within networks of prefrontal
      cortical (PFC) neurons, evident during delay periods in WM tasks. Stimulation of
      postsynaptic alpha2A adrenoceptors (alpha2A-ARs) is critical for WM. We report
      that alpha2A-AR stimulation strengthens WM through inhibition of cAMP, closing
      Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channels and
      strengthening the functional connectivity of PFC networks. Ultrastructurally, HCN
      channels and alpha2A-ARs were colocalized in dendritic spines in PFC. In
      electrophysiological studies, either alpha2A-AR stimulation, cAMP inhibition or
      HCN channel blockade enhanced spatially tuned delay-related firing of PFC
      neurons. Conversely, delay-related network firing collapsed under conditions of
      excessive cAMP. In behavioral studies, either blockade or knockdown of HCN1
      channels in PFC improved WM performance. These data reveal a powerful mechanism
      for rapidly altering the strength of WM networks in PFC.

PMID- 17448998
TI  - Endocytosis optimizes the dynamic localization of membrane proteins that regulate
      cortical polarity.
AB  - Diverse cell types require the ability to maintain dynamically polarized membrane
      protein distributions through balancing transport and diffusion. However, design
      principles underlying dynamically maintained cortical polarity are not well
      understood. Here we constructed a mathematical model for characterizing the
      morphology of dynamically polarized protein distributions. We developed
      analytical approaches for measuring all model parameters from single-cell
      experiments. We applied our methods to a well-characterized system for studying
      polarized membrane proteins: budding yeast cells expressing activated Cdc42. We
      found that a balance of diffusion, directed transport, and endocytosis was
      sufficient for accurately describing polarization morphologies. Surprisingly, the
      model predicts that polarized regions are defined with a precision that is nearly
      optimal for measured endocytosis rates and that polarity can be dynamically
      stabilized through positive feedback with directed transport. Our approach
      provides a step toward understanding how biological systems shape spatially
      precise, unambiguous cortical polarity domains using dynamic processes.

PMID- 17449000
TI  - SnapShot: mTOR signaling.

PMID- 17448999
TI  - The BH3-only protein bid is dispensable for DNA damage- and replicative stress
      induced apoptosis or cell-cycle arrest.
AB  - Bid, a caspase-activated proapoptotic BH3-only protein, is essential for Fas
      induced hepatocyte destruction. Recent studies published in Cell produced
      conflicting results, indicating that loss of Bid either protects or enhances
      apoptosis induced by DNA damage or replicative stress. To resolve this
      controversy, we generated novel Bid-deficient mice on an inbred C57BL/6
      background and removed the drug-selection cassette from the targeted locus. Nine
      distinct cell types from these Bid-deficient mice underwent cell-cycle arrest and
      apoptosis in a manner indistinguishable from control WT cells in response to DNA
      damage or replicative stress. Moreover, we found that even cells from the
      original Bid-deficient mice responded normally to these stimuli, indicating that
      differences in genetic background or the presence of a strong promoter within the
      targeted locus are unlikely to explain the differences between our results and
      those reported previously. We conclude that Bid has no role in DNA damage- or
      replicative stress-induced apoptosis or cell-cycle arrest.

PMID- 17449001
TI  - Effectiveness of the gold weight trial procedure in predicting the ideal weight
      for lid loading in facial palsy: a prospective study.
AB  - PURPOSE: To evaluate the effectiveness of the gold weight trial procedure in
      predicting postoperative eyelid closure after gold weight implantation surgery
      for facial palsy. DESIGN: Prospective, interventional case series. METHODS:
      Patients with facial palsy undergoing gold weight implantation were enrolled
      prospectively to undergo the standard gold weight trial procedure. The criteria
      for ideal gold weight were defined before surgery as a minimum 50% reduction in
      lagophthalmos without induction of more than 2 mm ptosis during the trial
      procedure. The corrected weight (ideal gold weight + 0.2 g) was implanted in the
      pretarsal space. The main outcome measure was reduction in lagophthalmos
      according to predefined criteria at six weeks after surgery. RESULTS: Thirty eyes
      of 29 patients underwent gold weight implantation. The mean age at surgery was
      41.6 years, and the median predicted ideal gold weight was 1.2 g. The mean
      preoperative lagophthalmos of 7 mm reduced to 2.3 mm at six weeks after surgery.
      As defined by the success criteria, undercorrection was noted in nine eyes (30%)
      at six weeks after surgery. A preoperative lagophthalmos of 8 mm or more was
      noted in seven (77.8%) of nine eyes in the undercorrection group, compared with
      six (28.6%) of 21 eyes in the success group. Six of the nine failures required
      implant exchange. CONCLUSIONS: The ideal gold weight as estimated by the trial
      procedure (with 0.2 g correction factor) led to undercorrection in 30% cases.
      Undercorrection was common (78%) in patients with preoperative lagophthalmos of
      more than 8 mm.

PMID- 17449002
TI  - Ultrastructural findings in the primate eye after intravitreal injection of
      bevacizumab.
AB  - PURPOSE: To examine the ultrastructural effect of intravitreal bevacizumab on
      primate eyes with particular focus set on the choriocapillaris and to examine the
      influence of vascular endothelial growth factor (VEGF) inhibition on endothelial
      cell fenestration. DESIGN: Animal study. METHODS: Four Cynomolgus monkeys
      received an intravitreal injection of 1.25 mg bevacizumab. The eyes were
      enucleated and prepared for light and electron microscopy on days one, four,
      seven, and 14. Control eyes remained untreated. Choriocapillaris endothelial cell
      fenestrations were quantified. RESULTS: Choriocapillaris endothelial cell
      fenestrations were significantly reduced after intravitreal injection of
      bevacizumab. Fenestration was lowest on day four (15.9 +/- 6.7 per 25 microm) and
      increased again from days seven to 14, but was still significantly lower than in
      the control (66.2 +/- 9.5 per 25 microm). Densely packed thrombocytes and
      leukocytes regionally occluded the choriocapillaris lumen of treated eyes. On day
      one an increased number of leukocytes filled in the choriocapillaris lumen.
      Photoreceptors were damaged in two of 40 light microscopic sections. On days one
      to seven, choroidal melanocytes contained giant melanosomes. None of these
      described features was found in controls. CONCLUSIONS: Intravitreal bevacizumab
      causes ultrastructural changes in the choriocapillaris of primate eyes. A
      significant reduction of choriocapillaris endothelial cell fenestrations is seen
      as early as 24 hours after injection and their number increases again after two
      weeks. These findings may play a role in the early clinical effect of
      intravitreal bevacizumab for macular edema. Because an increased risk of
      circulation disturbances in the choriocapillaris cannot be excluded, patients
      should be carefully monitored.

PMID- 17449003
TI  - Monitoring repair of DNA damage in cell lines and human peripheral blood
      mononuclear cells.
AB  - We introduce a method to follow DNA repair that is suitable for both clinical and
      laboratory samples. An episomal construct with a unique 8-oxoguanine (8-oxoG)
      base at a defined position was prepared in vitro using single-stranded phage
      harboring a 678-bp tract from exons 5 to 9 of the human P53 gene. Mixing curve
      experiments showed that the real-time PCR method has a linear response to damage,
      suggesting that it is useful for DNA repair studies. The episomal construct with
      a unique 8-oxoG base was introduced into AD293 cells or human peripheral blood
      mononuclear cells, and plasmids were recovered as a function of time. The
      quantitative real-time PCR assay demonstrated that repair of the 8-oxoG was 80%
      complete in less than 48 h in AD293 cells. Transfection of small interfering RNAs
      down-regulated OGG1 expression in AD293 cells and reduced the repair of 8-oxoG to
      30%. Transfection of the episome into unstimulated white blood cells showed that
      8-oxoG repair had a half-life of 2 to 5h. This method is a rapid, reproducible,
      and robust way to monitor repair of specific adducts in virtually any cell type.

PMID- 17449004
TI  - Engineering a noncarrier to a highly efficient carrier peptide for noncovalently
      delivering biologically active proteins into human cells.
AB  - Noncovalent protein delivery into cells via peptide carriers is an emerging
      concept. Only a handful of such peptides are known. To address various
      limitations associated with protein delivery for therapeutic purposes, a greater
      number of different delivery peptides would be required. No general method exists
      for creating such peptides. By combining a sequence of 16 lysine residues (K16)
      with the signal peptide (SP) sequence of Kaposi's fibroblast growth factor (K
      FGF), we have synthesized a peptide (K16SP) that efficiently and noncovalently
      delivers functionally intact proteins (immunoglobulin G molecules, beta
      galactosidase, and green fluorescent protein) into mammalian cells. The peptides
      K16 and SP each alone did not show any noncovalent protein-carrying capacity.
      K16SP appears to be nontoxic to cells and three to four times more efficient than
      a commercially available peptide reagent. Our approach offers proof-of-concept of
      a general strategy for creating a diverse array of peptide carriers for eventual
      therapeutic applications.

PMID- 17449005
TI  - Flow injection analysis of blood L-lactate by using a Prussian Blue-based
      biosensor as amperometric detector.
AB  - An amperometric l-lactate biosensor was fabricated by confining lactate oxidase
      in a Prussian Blue-modified electrode with a Nafion membrane. The detector was
      assembled in a flow injection apparatus and operated at -0.1 V. Conditions for
      optimal electrode response were determined by investigating the influence of the
      amount of immobilized enzyme, the sample volume, and the flow rate. At the
      established operational conditions, the biosensor exhibited negligible response
      from interfering species usually present in biological fluids. The stability of
      the biosensor was also investigated, and its sensitivity was maintained unchanged
      at certain experimental conditions. l-Lactate was determined in blood samples,
      and the influence of physical exercise on the results was clearly evidenced,
      demonstrating that the proposed amperometric detector is suitable for monitoring
      changes in the l-lactate levels in biological fluids.

PMID- 17449006
TI  - Enhance the efficiency of single-strand conformation polymorphism analysis by
      short polyacrylamide gel and modified silver staining.

PMID- 17449007
TI  - Comparison of nucleic acid targets prepared from total RNA or poly(A) RNA for DNA
      oligonucleotide microarray hybridization.
AB  - The aim of this work was to compare DNA microarray results using either total RNA
      or affinity-purified poly(A) RNA from the same biological sample for target
      preparation. The high-density oligonucleotide microarrays of both Agilent
      Technologies (based on two-color detection) and Applied Biosystems (based on
      single-color detection) were evaluated. Real-time quantitative PCR was used to
      quantify messenger RNA (mRNA) and ribosomal RNA (rRNA) at different stages of
      target preparations. Poly(A) RNA versus total RNA target hybridizations exhibited
      slightly lower correlation coefficients than did self versus self hybridizations
      (i.e., poly(A) RNA targets vs. poly(A) RNA targets or total RNA targets vs. total
      RNA targets). Only a small fraction of all transcripts appeared to be
      significantly over- or underrepresented when total RNA targets or poly(A) RNA
      targets from the same biological sample were compared. Therefore, the conclusion
      is that poly(A) affinity purification from total RNA can be omitted during target
      preparation for routine mRNA expression analysis using high-density
      oligonucleotide microarrays. Among consistently overrepresented transcripts in
      total RNA targets were histone mRNAs known to lack poly(A) tails. Therefore,
      structurally exceptional RNA species can be identified by comparing targets
      derived from either poly(A) RNA or total RNA using microarray hybridization.

PMID- 17449008
TI  - The effect of prism orientation on the indentation testing of human molar enamel.
AB  - Recent nanoindentation studies have demonstrated that the hardness and Young's
      modulus of human molar enamel decreases by more than 50% on moving from the
      occlusal surface to the dentine-enamel junction on cross-sectional samples.
      Possible sources of these variations are changes in local chemistry,
      microstructure, and prism orientation. This study investigates the latter source
      by performing nanoindentation tests at two different orientations relative to the
      hydroxyapatite prisms: parallel and perpendicular. A single sample volume was
      tested in order to maintain a constant chemistry and microstructure. The
      resulting data show very small differences between the two orientations for both
      hardness and Young's modulus. The 1.5-3.0% difference is significantly less than
      the standard deviations found within the data set. Thus, the variations in
      hardness and Young's modulus on cross-sectional samples of human molar are
      attributed to changes in local chemistry (varying levels of mineralization,
      organic matter, and water content) and changes in microstructure (varying volume
      fractions of inorganic crystals and organic matrix). The impact of prism
      orientation on mechanical properties measured at this scale by nanoindentation
      appears to be minimal.

PMID- 17449009
TI  - Requirement of duplicated operons for maximal metabolism of phthalate by
      Rhodococcus sp. strain DK17.
AB  - The operons encoding the transformation of phthalate to protocatechuate are
      duplicated and present on two different megaplasmids [pDK2 (330 kb) and pDK3 (750
      kb)] in Rhodococcus sp. strain DK17. RT-PCR experiments using gene-specific
      primers showed that both the pDK2- and the pDK3-encoded dihydroxyphthalate
      decarboxylase genes are simultaneously expressed during growth on phthalate. The
      doubling time of the pDK2-cured mutant strain DK176 in minimal liquid medium with
      5mM phthalate is 52.5% of that of the wild-type strain DK17. The data indicate
      that both copies of the phthalate operon are equally functional in DK17, and gene
      dosage is the main reason for slower growth of DK176 on phthalate.

PMID- 17449010
TI  - RecA-ssDNA filaments supercoil in the presence of single-stranded DNA-binding
      protein.
AB  - Using atomic force microscopy (AFM), we find that RecA-single-stranded DNA (RecA
      ssDNA) filaments, in the presence of single-stranded DNA-binding (SSB) protein,
      organize into left-handed bundles, which differ from the previously reported
      disordered aggregates formed when SSB is excluded from the reaction. In addition,
      we see both left- and right-handedness on bundles of two filaments. These two
      filament supercoils, individual filaments, and other smaller bundles further
      organize into more complicated bundles, showing overall left-handedness which
      cannot be explained by earlier arguments that presumed supercoiling is absent in
      RecA-ssDNA filaments. This novel finding and our previous results regarding
      supercoiling of RecA-double-stranded DNA (RecA-dsDNA) filaments are, however,
      consistent with each other and can possibly be explained by the intrinsic
      tendency of RecA-DNA filaments, in their fully coated form, to order themselves
      into helical bundles, independent of the DNA inside the filaments (ssDNA or
      dsDNA). RecA-RecA interactions may dominate the bundling process, while the
      original conformation of DNA inside filaments and other factors (mechanical
      properties of filaments, concentration of filaments, and Mg(2+) concentration)
      could contribute to the variation in the appearance and pitch of supercoils. The
      tendency of RecA-DNA filaments to form ordered supercoils and their presence
      during strand exchange suggest a possible biological importance of supercoiled
      filaments.

PMID- 17449011
TI  - Involvement of c-Jun N-terminal kinases activation in diabetic embryopathy.
AB  - The mechanisms for diabetic embryopathy are not well understood. JNK1/2
      activation is increased in diabetic embryopathy, and antioxidants abolish JNK
      activation, and thus, ameliorate diabetic embryopathy. Phosphorylated SEK1 were
      significantly elevated in malformed embryos from diabetic mouse. In a dose
      dependent manner, JNK inhibitor (SP600125) significantly reduced hyperglycemia
      induced embryopathy. Malformation rates in embryos from the diabetic WT group
      were 15.6-fold higher than that in the non-diabetic WT control group. Jnk2 null
      mutant (JNKKO mice) was associated with a 71% reduction in the malformation rate
      of embryos under maternal diabetic conditions. Embryos cultured in 0.5mM sorbitol
      (JNK activator) had a malformation rate that was significantly higher than that
      of the control group. Pharmacological and genetic evidence from the present
      studies strongly support JNK activation being an indispensable mediator of
      diabetic embryopathy. JNK activation itself is sufficient to induce embryonic
      anomalies, and thus mimics the teratogenic effect of hyperglycemia.

PMID- 17449012
TI  - The kinesin related motor protein, Eg5, is essential for maintenance of pre
      implantation embryogenesis.
AB  - Eg5 is a plus end directed kinesin related motor protein (KRP) previously shown
      to be involved in the assembly and maintenance of the mitotic spindle. KRPs are
      molecular motors capable of generating forces upon microtubules (MTs) in dividing
      cells and driving structural rearrangements necessary in the developing spindle.
      In vitro experiments demonstrate that loss of Eg5 results in cell cycle arrest
      and defective centrosome separation resulting in the development of monopolar
      spindles. Here we describe mice with a genetrap insertion in Eg5. Heterozygous
      mutant mice appear phenotypically normal. In contrast, embryos homozygous for the
      Eg5 null allele recovered at embryonic days 2.5-3.5 display signs of a
      proliferation defect as reduced cell numbers and failure of compaction and
      progression to the blastocyst stage was observed. These data, in conjunction with
      previous in vitro data, suggest that loss of Eg5 results in abnormal spindle
      structure, cell cycle arrest and thereby reduced cell proliferation of early
      cleavage pre-implantation embryos. These observations further support the
      conclusion that Eg5 is essential for cell division early in mouse development,
      and that maternal contribution may sustain the embryo through the maternal to
      zygotic transition at which point supplies of functional Eg5 are exhausted,
      preventing further cell cleavage.

PMID- 17449013
TI  - PPARalpha is a potential therapeutic target of drugs to treat circadian rhythm
      sleep disorders.
AB  - Recent progress at the molecular level has revealed that nuclear receptors play
      an important role in the generation of mammalian circadian rhythms. To examine
      whether peroxisome proliferator-activated receptor alpha (PPARalpha) is involved
      in the regulation of circadian behavioral rhythms in mammals, we evaluated the
      locomotor activity of mice administered with the hypolipidemic PPARalpha ligand,
      bezafibrate. Circadian locomotor activity was phase-advanced about 3h in mice
      given bezafibrate under light-dark (LD) conditions. Transfer from LD to constant
      darkness did not change the onset of activity in these mice, suggesting that
      bezafibrate advanced the phase of the endogenous clock. Surprisingly, bezafibrate
      also advanced the phase in mice with lesions of the suprachiasmatic nucleus (SCN;
      the central clock in mammals). The circadian expression of clock genes such as
      period2, BMAL1, and Rev-erbalpha was also phase-advanced in various tissues
      (cortex, liver, and fat) without affecting the SCN. Bezafibrate also phase
      advanced the activity phase that is delayed in model mice with delayed sleep
      phase syndrome (DSPS) due to a Clock gene mutation. Our results indicated that
      PPARalpha is involved in circadian clock control independently of the SCN and
      that PPARalpha could be a potent target of drugs to treat circadian rhythm sleep
      disorders including DSPS.

PMID- 17449014
TI  - Comparative analysis of cell surface proteins in chronic and acute leukemia cell
      lines.
AB  - This study was designed to identify the cell surface protein markers that can
      differentiate between chronic myeloid leukemia (CML) and acute promyelocytic
      leukemia cells (APL). The differentially expressed plasma membrane proteins were
      analyzed between CML cell line (K562) and APL cell line (NB4) using the
      comparative proteomic approach. The cell membrane proteins were enriched by
      labeling with a membrane-impermeable biotinylation reagent, sulfo-NHS-SS-Biotin,
      and subjected to liquid chromatography tandem mass spectrometry (LC-MS/MS). By
      comparative proteomic analysis of K562 and NB4 cells, we identified 25 membrane
      and 14 membrane-associated proteins. The result of LC-MS/MS combined with
      chemical tagging method was validated by confirming the expression and
      localization of one of the differentially expressed plasma membrane proteins,
      CD43, by FACS and confocal microscopy. Our results indicate that CD43 could be a
      potential candidate for differentiating CML from APL.

PMID- 17449015
TI  - Pharmacological inhibition of PARP-1 reduces alpha-synuclein- and MPP+-induced
      cytotoxicity in Parkinson's disease in vitro models.
AB  - Treatments based on pharmacological inhibition of poly(ADP-ribose) polymerase-1
      (PARP-1) have been suggested for a broad variety of human disorders, including
      Parkinson's disease (PD). The neuroprotective effects underlying the efficacy of
      PARP-1 inhibitors in PD models suggest a role for PARP-1 in neurodegeneration. In
      this study, we assessed the efficacy of PARP-1 inhibition in two distinct PD
      models. First, we tested a panel of small molecule PARP-1 inhibitors in alpha
      synuclein (aSyn) cytotoxicity assay, where we observed compound-dependent
      ameliorating effects. Next, we tested the same panel in primary ventral
      mesencephalic neuronal cultures, treated with MPP(+). Dopaminergic neurons, the
      primary cells affected in PD, were selected and subjected to analysis. A
      significant ameliorating effect was achieved only with a highly potent PARP-1
      inhibitor. Our data implicates aberrant PARP-1 function in different pathways of
      neurodegeneration. Further, our results suggest a rationale for the development
      of highly potent, bio-available, brain-penetrable PARP-1 inhibitors to provide
      therapeutic benefits for Parkinson's patients.

PMID- 17449016
TI  - Lycopene binds PDGF-BB and inhibits PDGF-BB-induced intracellular signaling
      transduction pathway in rat smooth muscle cells.
AB  - Cardiovascular diseases (CVDs) result from the sub-endothelial accumulation of
      inflammatory cells and smooth muscle cells (SMCs). Lycopene, a natural compound
      from tomato, has been suggested to play a role in CVD prevention. However, its
      action mechanism is still largely unknown. In this study, we examined the effect
      of lycopene on SMCs. We found that preincubation of PDGF-BB with lycopene
      resulted in a marked inhibition on PDGF-BB-induced PDGF receptor-beta (PDGFR
      beta), PLCgamma, and ERK1/2 phosphorylation in rat A10 SMCs and primary cultured
      aortic SMCs. In striking contrast, lycopene did not influence EGF-induced ERK1/2
      phosphorylation. Surprisingly, further analysis indicates that lycopene could
      directly bind PDGF-BB and inhibit PDGF-BB-SMC interaction, as determined by dot
      binding assay and Western blotting. In functional studies, lycopene inhibited
      PDGF-BB-induced SMC proliferation and migration toward gelatin and collagen at
      concentrations ranging from 2 to 10 microM. On the contrary, lycopene did not
      inhibit bFGF- and VEGF-induced endothelial cell migration. Gelatin zymography
      demonstrated that lycopene's effect on SMC migration was not due to the
      inhibition of matrix metalloproteinases (MMPs). Taken together, our results
      provide the first evidence showing that lycopene inhibits PDGF-BB-induced
      signaling, proliferation and migration in rat A10 and aortic SMCs. One of the
      action mechanisms is that lycopene is capable of binding PDGF-BB and inhibiting
      its interaction with SMC, which is quite different from those previously
      developed PDGFR-beta antagonists. The results presented here may help us to
      better understand the beneficial effects of lycopene in CVD prevention.

PMID- 17449017
TI  - High content screen microscopy analysis of A beta 1-42-induced neurite outgrowth
      reduction in rat primary cortical neurons: neuroprotective effects of alpha 7
      neuronal nicotinic acetylcholine receptor ligands.
AB  - beta-Amyloid peptide 1-42 (A beta(1-42)) is generated from amyloid precursor
      protein (APP) and associated with neurodegeneration in Alzheimer's disease (AD).
      A beta(1-42) has been shown to be cytotoxic when incubated with cultured neurons.
      However, APP transgenic mice over-expressing A beta(1-42) do not show substantial
      loss of neurons, despite deficits in learning and memory. It is thus emerging
      that A beta(1-42)-induced memory deficits may involve subtler neuronal
      alternations leading to synaptic deficits, prior to frank neurodegeneration in AD
      brains. In this study, high content screen (HCS) microscopy, an advanced high
      throughput cellular image processing and analysis technique, was utilized in
      establishing an in vitro model of A beta(1-42)-induced neurotoxicity utilizing
      rat neonatal primary cortical cells. Neurite outgrowth was found to be
      significantly reduced by A beta(1-42) (300 nM to 30 microM), but not by the
      scrambled control peptide control, in a time- and concentration-dependent manner.
      In contrast, no reduction in the total number of neurons was observed. The A
      beta(1-42)-induced reduction of neurite outgrowth was attenuated by the NMDA
      receptor antagonist memantine and the alpha 7 nicotinic acetylcholine receptor
      (nAChR) selective agonist PNU-282987. Interestingly, the alpha 7 nAChR antagonist
      methyllycaconitine also significantly prevented reduction in A beta(1-42)-induced
      neurite outgrowth. The observed neuroprotective effects could arise either from
      interference of A beta(1-42) interactions with alpha 7 nAChRs or by modification
      of receptor-mediated signaling pathways. Our studies demonstrate that reduction
      of neurite outgrowth may serve as a model representing A beta(1-42)-mediated
      neuritic and synaptic toxicity, which, in combination of HCS, provides a high
      throughput cell-based assay that can be used to evaluate compounds with
      neuroprotective properties in neurons.

PMID- 17449018
TI  - A mutation in calsequestrin, CASQ2D307H, impairs Sarcoplasmic Reticulum Ca2+
      handling and causes complex ventricular arrhythmias in mice.
AB  - OBJECTIVE: A naturally-occurring mutation in cardiac calsequestrin (CASQ2) at
      amino acid 307 was discovered in a highly inbred family and hypothesized to cause
      Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The goal of this
      study was to establish a causal link between CASQ2(D307H) and the CPVT phenotype
      using an in vivo model. METHODS AND RESULTS: Cardiac-specific expression of the
      CASQ2(D307H) transgene was achieved using the alpha-MHC promoter. Multiple
      transgenic (TG) mouse lines expressing CASQ2(D307H) from 2- to 6-fold possess
      structurally normal hearts without any sign of hypertrophy. The hearts displayed
      normal ventricular function. Myocytes isolated from TG mice had diminished I(Ca)
      induced Ca2+ transient amplitude and duration, as well as increased Ca2+ spark
      frequency. These myocytes, when exposed to isoproterenol and caffeine, displayed
      disturbances in their rhythmic Ca2+ oscillations and membrane potential, and
      delayed afterdepolarizations. ECG monitoring revealed that TG mice challenged
      with isoproterenol and caffeine developed complex ventricular arrhythmias,
      including non-sustained polymorphic ventricular tachycardia. CONCLUSIONS: The
      findings of the present study demonstrate that expression of mutant CASQ2(D307H)
      in the mouse heart results in abnormal myocyte Ca2+ handling and predisposes to
      complex ventricular arrhythmias similar to the CPVT phenotype observed in human
      patients.

PMID- 17449019
TI  - Investigation on the early events of apoptosis in senescent erythrocytes with
      special emphasis on intracellular free calcium and loss of phospholipid asymmetry
      in chronic renal failure.
AB  - BACKGROUND: The pathophysiological link between increased blood concentrations of
      factors responsible for the derangement and erythrocyte membrane functions in
      chronic renal failure (CRF) patients are not thoroughly elucidated. We studied
      the erythrocyte characteristics and phospholipid asymmetry loss in CRF patients
      with different grades of uremia and also examined the involvement of
      intracellular free Ca(2+) in early events of apoptosis in uremic erythrocytes.
      METHODS: The studied population consisted of 90, age and sex matched control
      subjects (Group I) and 238 CRF cases divided into 3 groups (Group II, III and IV)
      according to urea concentrations and complexity of secondary complications.
      Erythrocyte membrane fluidity determined by binding of MC540. Intracellular free
      Ca(2+) concentration was determined by the 2-wavelength method by using
      fluorescent calcium-sensitive probe FURA-2AM. Measurement of erythrocyte
      phosphatidylserine exposure by flow cytometry using Annexin V-FITC. RESULTS:
      Cholesterol shedding increased with increasing severity of uremic complications.
      Erythrocytes from Group II show mild echinocyte or formation of spicules on the
      erythrocyte membrane surface whereas in Group III and IV they were echinocytic.
      Binding of MC540 was significantly higher with progression of uremic
      complications. Surface charge of uremic erythrocyte membrane was significantly
      reduced when compared with control subjects. Intracellular free Ca(2+) was
      positively correlated with binding of MC540 and surface hydrophobicity. The
      phosphatidylserine exposure of erythrocytes was significantly higher (p<0.001) in
      uremic patients when compared with controls. CONCLUSIONS: Phosphatidylserine (PS)
      exposure erythrocytes were significantly increased in uremic patients when
      compared with controls. Uremic complications predisposes to membrane damages in
      erythrocytes.

PMID- 17449020
TI  - Guidelines are never perfect; however they need to be transparent.

PMID- 17449022
TI  - Reporting of cardiac troponin - problems with the 99th population percentile.

PMID- 17449021
TI  - Saliva collection method affects predictability of serum cortisol.
AB  - BACKGROUND: Measurement of cortisol is of particular importance for early
      diagnosis of adrenocorticotropic dysfunction and therapeutic monitoring. Saliva
      samples clearly present an easily manageable, non-invasive and anytime
      practicable assessment method of glucocorticoid production. The aims of the
      present study were to compare salivary cortisol collection method "Salivette"
      versus "passive drool", salivary cortisol concentrations with calculated free
      serum cortisol (FSC) and total serum cortisol (TSC) and the prediction of serum
      cortisol by salivary cortisol. METHODS: Saliva samples were collected by Sarstedt
      Salivette(R) and by passive drooling into plastic tubes. Salivary cortisol, TSC
      measurements and calculation of FSC concentrations as well were carried out
      simultaneously in 10 healthy volunteers on two consecutive days at six definite
      points of time (08.00-23.00). RESULTS: Significant differences of salivary
      cortisol concentrations dependent on the saliva collection method (F-test 6.45;
      p=0.0317) and points of times were found (F-test 41.19; p<0.0001). Stronger
      overall correlation was observed in Salivette-salivary cortisol vs. TSC (r=0.813)
      and FSC (r=0.836) as compared to passive drooling. Specifically, more significant
      correlations were established in Salivettes vs. TSC (8/12 points of time, 66.7%)
      and FSC (8/12 points of time, 66.7%) than in passive drooling (TSC: 1/12 points
      of time, 8.3% and FSC: 2/12 points of time, 16.7%). Importantly, cortisol in
      Salivettes was a better predictor for FSC and TSC than passive drooling.
      CONCLUSIONS: Our data indicate that salivary cortisol measurement with Salivettes
      is a reliable prediction method of total and calculated free serum cortisol
      levels. Moreover, it is a convenient method for saliva collection, handling and
      laboratory processing.

PMID- 17449023
TI  - Inhibition within a reference frame during the interpretation of spatial
      language.
AB  - Spatial terms such as right are potentially ambiguous because they can refer to
      different regions of space when defined by competing reference frames (e.g., my
      right within a relative reference frame versus an object's right within an
      intrinsic reference frame). In such situations, previous research has suggested
      that multiple reference frames are initially activated, followed by inhibition of
      the reference frame that is not ultimately selected to define the spatial term.
      Reference frames are complex multi-component representations, raising the
      question of exactly which components of the non-selected frame are inhibited. It
      is possible that the whole frame may be inhibited, including all axes and
      endpoints, or that only select endpoints and axes may be inhibited. Three
      experiments conducted using a negative priming paradigm revealed that only
      certain components of the non-selected reference frame were inhibited, consistent
      with the idea that some axes are privileged. These results also suggest that the
      components of a reference frame can be independently accessed. Implications for
      representing and accessing spatial information are discussed.

PMID- 17449024
TI  - Functional BMP receptor in endocardial cells is required in atrioventricular
      cushion mesenchymal cell formation in chick.
AB  - Transformation of atrioventricular (AV) canal endocardium into invasive
      mesenchyme correlates spatially and temporally with the expression of bone
      morphogenetic protein (BMP)-2 in the AV myocardium. We revealed the presence of
      mRNA of Type I BMP receptors, BMPR-1A (ALK3), BMPR-1B (ALK6) and ALK2 in chick AV
      endocardium at stage-14(-), the onset of epithelial to mesenchymal transformation
      (EMT), by RT-PCR and localized BMPR-1B mRNA in the endocardium by in situ
      hybridization. To circumvent the functional redundancies among the Type I BMP
      receptors, we applied dominant-negative (dn) BMPR-1B-viruses to chick AV explants
      and whole-chick embryo cultures to specifically block BMP signaling in AV
      endocardium during EMT. dnBMPR-1B-virus infection of AV endocardial cells
      abolished BMP-2-supported AV endocardial EMT. Conversely, caBMPR-1B-virus
      infection promoted AV endocardial EMT in the absence of AV myocardium. Moreover,
      dnBMPR-1B-virus treatments significantly reduced myocardially supported EMT in AV
      endocardial-myocardial co-culture. AV cushion mesenchymal cell markers, alpha
      smooth muscle actin (SMA), and TGFbeta3 in the endocardial cells were promoted by
      caBMPR-1B and reduced by dnBMPR-1B infection. Microinjection of the virus into
      the cardiac jelly in the AV canal at stage-13 in vivo (ovo) revealed that the
      dnBMPR-1B-virus-infected cells remained in the endocardial epithelium, whereas
      caBMPR-1B-infected cells invaded deep into the cushions. These results provide
      evidence that BMP signaling through the AV endocardium is required for the EMT
      and the activation of the BMP receptor in the endocardium can promote AV EMT in
      the chick.

PMID- 17449025
TI  - Restricted co-expression of Dlk1 and the reciprocally imprinted non-coding RNA,
      Gtl2: implications for cis-acting control.
AB  - Dlk1 and Gtl2 are reciprocally imprinted neighboring genes located within a 1 Mb
      imprinted domain on murine distal chromosome 12. The two genes are expressed and
      developmentally regulated during mammalian embryogenesis. Dlk1/Pref1 encodes a
      transmembrane protein with homology to members of the Notch/Delta developmental
      signaling pathway and Gtl2 generates alternatively spliced poly-adenylated
      transcripts lacking a conserved open reading frame. An intergenic differentially
      methylated region (IG-DMR) located 13 kb upstream of Gtl2 has been shown to
      regulate imprinting throughout the domain by an as yet unknown mechanism. In
      order to gain insights into regulation at this domain and to compare it with
      imprinting control at other loci, we compared the expression profile of Dlk1 with
      Gtl2 during mouse embryogenesis in normal conceptuses and in those with
      uniparental disomy for chromosome 12. The expression profile of these genes
      suggests a causative role for Dlk1 and Gtl2 in the pathologies found in
      uniparental disomy animals, characterized by defects in skeletal muscle
      maturation, bone formation, placenta size and organization and prenatal
      lethality. Here, we show restricted overlap in cellular expression of these two
      genes throughout development. Dlk1 is imprinted and expressed in cell types
      within the lung, liver and placenta where Gtl2 is not expressed. Gtl2 is highly
      expressed in the central nervous system (CNS), whereas Dlk1 is found localized to
      specific regions such as the hypothalamus. Co-expression is observed in most of
      the mesodermal-derived tissues, notably the skeletal muscle where both genes are
      strongly co-expressed. In this tissue, Dlk1 shows a relaxation of imprinting with
      some expression from the maternal allele. These findings indicate that the
      general mechanism of imprinting at the stages analyzed is not through the co
      ordinate non-coding RNA or insulator mechanisms observed for other imprinted
      domains, and suggest that the two genes have independent tissue-specific
      functions.

PMID- 17449027
TI  - Localized activation of Src-family protein kinases in the mouse egg.
AB  - Recent studies in species that fertilize externally have demonstrated that
      fertilization triggers localized activation of Src-family protein kinases in the
      egg cortex. However, the requirement for Src-family kinases in activation of the
      mammalian egg is different from lower species and the objective of this study was
      to characterize changes in the distribution and activity of Src-family protein
      tyrosine kinases (PTKs) during zygotic development in the mouse.
      Immunofluorescence analysis of mouse oocytes and zygotes with an anti
      phosphotyrosine antibody revealed that fertilization stimulated accumulation of P
      Tyr-containing proteins in the egg cortex and that their abundance was elevated
      in the region overlying the MII spindle. In addition, the poles of the MII
      spindle exhibited elevated P-Tyr levels. As polar body extrusion progressed, P
      Tyr-containing proteins were especially concentrated in the region of cortex
      adjacent to the maternal chromatin and the forming polar body. In contrast, P-Tyr
      labeling of the spindle poles eventually disappeared as meiosis II progressed to
      anaphase II. In approximately 24% of cases, the fertilizing sperm nucleus was
      associated with increased P-Tyr labeling in the overlying cortex and oolemma. To
      determine whether Src-family protein tyrosine kinases could be responsible for
      the observed changes in the distribution of P-Tyr containing proteins, an
      antibody to the activated form of Src-family PTKs was used to localize activated
      Src, Fyn or Yes. Activated Src-family kinases were found to be strongly
      associated with the meiotic spindle at all stages of meiosis II; however, no
      concentration of labeling was evident at the egg cortex. The absence of cortical
      Src-family PTK activity continued until the blastocyst stage when strong cortical
      activity became evident. At the pronuclear stage, activated Src-family PTKs
      became concentrated around the pronuclei in close association with the nuclear
      envelope. This pattern was unique to the earliest stages of development and
      disappeared by the eight cell stage. Functional studies using chemical inhibitors
      and a dominant-negative Fyn construct demonstrated that Src-family PTKs play an
      essential role in completion of meiosis II following fertilization and
      progression from the pronuclear stage into mitosis. These data suggest that while
      Src-family PTKs are not required for fertilization-induced calcium oscillations,
      they do play a critical role in development of the zygote. Furthermore,
      activation of these kinases in the mouse egg is limited to distinct regions and
      occurs at specific times after fertilization.

PMID- 17449028
TI  - Impaired arginine-vasopressin-induced aldosterone release from adrenal gland
      cells in mice lacking the vasopressin V1A receptor.
AB  - We examined aldosterone release in response to stimulation with arginine
      vasopressin (AVP) using adrenal gland cells. AVP caused a significant increase in
      aldosterone release from the dispersed adrenal gland cells of wild-type mice
      (V1AR+/+) at concentrations from 0.1 microM to 1 microM. In contrast, AVP-induced
      aldosterone release was impaired in adrenal gland cells from mice lacking the
      vasopressin V1A receptor (V1AR-/-), while adrenocorticotropic hormone (ACTH)
      induced aldosterone release in V1AR-/- mice was not significantly different from
      that in V1AR+/+ mice. In addition, a vasopressin V1A receptor-selective
      antagonist 1-[1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl]-3,4-dihydro-2(1H)
      quinolinone (OPC-21268) potently inhibited AVP-induced aldosterone release. Thus,
      our study clearly demonstrates that AVP-induced aldosterone release from adrenal
      gland cells is mediated via the vasopressin V1A receptor in mice.

PMID- 17449026
TI  - Amphibian metamorphosis.

PMID- 17449029
TI  - Structure-based identification of small molecule compounds targeting cell
      cyclophilin A with anti-HIV-1 activity.
AB  - Cyclophilin A acts as protein folding chaperones and intracellular transports in
      many cellular processes. Previous studies have shown that cyclophilin A can
      interact with HIV-1 (human immunodeficiency virus type 1) gag protein and enhance
      viral infectivity. Many cyclophilin A inhibitors such as cyclosporin A can
      inhibit HIV-1 replication in vitro. Here, we report a structure-based
      identification of novel non-peptidic cyclophilin A inhibitors as anti-HIV lead
      compounds. Following a computer-aided virtual screening and subsequent surface
      plasmon resonance (SPR) analysis, 12 low molecular weight cyclophilin A ligands
      were selected for further evaluation of their in vitro inhibition of peptidyl
      prolyl cis-trans isomerase (PPIase) activity of cyclophilin A and HIV-1
      replication. Five of these compounds (FD5, FD8, FD9, FD10 and FD12) exhibited
      inhibition against both PPIase activity and HIV-1 infection. These active
      compounds will be used as leads for structure and activity relationship (SAR) and
      optimization studies in order to design more effective anti-HIV-1 therapeutics,
      and as probes for investigating the effect of cyclophilins on HIV-1 replication.

PMID- 17449030
TI  - Cortactin involvement in the keratinocyte growth factor and fibroblast growth
      factor 10 promotion of migration and cortical actin assembly in human
      keratinocytes.
AB  - Keratinocyte growth factor (KGF/FGF7) and fibroblast growth factor 10
      (FGF10/KGF2) regulate keratinocyte proliferation and differentiation by binding
      to the tyrosine kinase KGF receptor (KGFR). KGF induces keratinocyte motility and
      cytoskeletal rearrangement, whereas a direct role of FGF10 on keratinocyte
      migration is not clearly established. Here we analyzed the motogenic activity of
      FGF10 and KGF on human keratinocytes. Migration assays and immunofluorescence of
      actin cytoskeleton revealed that FGF10 is less efficient than KGF in promoting
      migration and exerts a delayed effect in inducing lamellipodia and ruffles
      formation. Both growth factors promoted phosphorylation and subsequent membrane
      translocation of cortactin, an F-actin binding protein involved in cell
      migration; however, FGF10-induced cortactin phosphorylation was reduced, more
      transient and delayed with respect to that promoted by KGF. Cortactin
      phosphorylation induced by both growth factors was Src-dependent, while its
      membrane translocation and cell migration were blocked by either Src and PI3K
      inhibitors, suggesting that both pathways are involved in KGF- and FGF10
      dependent motility. Furthermore, siRNA-mediated downregulation of cortactin
      inhibited KGF- and FGF10-induced migration. These results indicate that cortactin
      is involved in keratinocyte migration promoted by both KGF and FGF10.

PMID- 17449031
TI  - Changes in the balance of the tissue inhibitor of matrix metalloproteinases
      (TIMPs)-1 and -3 may promote keratocyte apoptosis in keratoconus.
AB  - Keratoconus is a disease in which the central cornea becomes thinned. This could
      result from corneal stromal cell apoptosis or be induced or perpetuated by the
      activation of matrix degrading enzymes, particularly members of the matrix
      metalloproteinase (MMP) family. In some circumstances, the MMP inhibitors TIMP-1
      and TIMP-3 exhibit anti-apoptotic and pro-apoptotic properties, respectively.
      Because they potentially influence keratoconus progression, the effects of TIMP-1
      and TIMP-3 on stromal cell viability were investigated. The TIMP-1 and TIMP-3
      proteins were over-expressed in cultured corneal stromal cells by using the
      adenoviral vectors RAdTIMP-1 and RAdTIMP-3 and quantified by enzyme-linked
      immunosorbant assay (ELISA). Apoptotic cells were detected by TUNEL and caspase-3
      activity. The anti-apoptotic effects of TIMP-1 were investigated by co-infecting
      it with RAdTIMP-1 and RAdTIMP-3 and by adding TIMP-1 protein to stromal cell
      cultures prior to infecting them with RAdTIMP-3. Immunohistochemistry was used to
      localise and determine relative numbers of apoptotic and TIMP producing stromal
      cells in sections of normal and keratoconic corneas. The results showed that over
      expression of TIMP-3 induced apoptosis in corneal stromal cell cultures. Up
      regulated TIMP-1 production or the addition of exogenous TIMP-1 protein prevented
      stromal cell overgrowth, changed stromal cell morphology and reduced the extent
      of TIMP-3 induced apoptosis. Localised relative concentrations of TIMP-1/TIMP-3
      could thus determine whether these cells remain viable or become apoptotic. This
      may be relevant to the keratoconic condition since significantly more apoptotic
      cells were identified in the anterior stroma of keratoconic corneas than normal
      corneas and the majority of theTIMP-1 and TIMP-3 producing stromal cells were
      also located in this region.

PMID- 17449032
TI  - Leishmania (Viannia) braziliensis: epidemiology of canine cutaneous leishmaniasis
      in the State of Parana (Brazil).
AB  - The present study examines the role that dogs play in the maintenance of the
      Leishmania cycle in the State of Parana, Southern Brazil. Dogs were examined in
      three regions where cutaneous leishmaniasis is endemic or epidemic (R1-Vale da
      Ribeira; R2-Central region of Parana State and R3-Northern region). To determine
      serum prevalence rates ELISA was used. In regions endemic for Trypanosoma cruzi
      (R1 and R3), serum from dogs seroreactive towards Leishmania antigen was
      subjected to T. cruzi adsorption in order to eliminate cross-reaction with common
      antigen epitopes. Concomitantly, dogs with cutaneous lesions were biopsied to
      isolate and identify parasites using RAPD. Leishmania were classified by the
      phenetic method using the Jaccard coefficient of similarity, and grouped by
      Unweighted Pair-Group Method using an Arithmetic Average (UPGMA). A total of 410
      dogs were studied. In R1 (Vale da Ribeira) 159 dogs were evaluated of which 10
      had anti-Leishmania antibody. In R2 (Central Parana), 39 animals were examined of
      which 8 were seropositive. In R3 (the North) 212 dogs were evaluated of which 39
      animals were seropositive. Thirteen dogs had cutaneous lesions and the parasites
      were isolated from a dog with mucocutaneous lesion in R1, two animals with simple
      skin lesions in R2 and 10 dogs with multiple lesions in R3. The identification of
      the parasite by molecular methods showed it to be L. (Viannia) braziliensis.
      Based on this information, the role of domestic dogs in Leishmania infection of
      cutaneous leishmaniasis in Parana is discussed.

PMID- 17449033
TI  - Specificity of alphaA-crystallin binding to destabilized mutants of betaB1
      crystallin.
AB  - To elucidate the structural and energetic basis of attractive protein
      interactions in the aging lens, we investigated the binding of destabilized
      mutants of betaB1-crystallin to the lens chaperones, alpha-crystallins. We show
      that the mutations enhance the binding affinity to alphaA- but not alphaB
      crystallin at physiological temperatures. Complex formation disrupts the dimer
      interface of betaB1-crystallin consistent with the binding of a monomer. Binding
      isotherms obtained at increasing concentrations of betaB1-crystallin deviate from
      a classic binding equilibrium and display cooperative-like behavior. In the
      context of betaB1-crystallin unfolding equilibrium, these characteristics are
      reflective of the concentration-dependent change in the population of a dimeric
      intermediate that has low affinity to alphaA-crystallin. In the lens, where alpha
      crystallin binding sites are not regenerated, this may represent an added
      mechanism to maintain lens transparency.

PMID- 17449034
TI  - Gestational hypertension in pregnancies supported by infertility treatments: role
      of infertility, treatments, and multiple gestations.
AB  - OBJECTIVE: To investigate the association between infertility treatments and
      gestational hypertension and preeclampsia. DESIGN: Retrospective observational
      cohort. SETTING: General population, United States and Canada. PATIENT(S): Five
      thousand one hundred fifty-one women with non-malformed infants participating in
      the Slone Epidemiology Center Birth Defects Study between 1998 and 2006.
      INTERVENTION(S): Women were interviewed within 6 months after delivery about
      sociodemographic and medical factors, about the onset of gestational hypertension
      and preeclampsia, and about infertility treatments. MAIN OUTCOME MEASURE(S): We
      estimated relative risks and 95% confidence intervals by using unconditional
      logistic regression. RESULT(S): The incidence of gestational hypertension was
      8.9% (423/4,762) among women without infertility treatments and was 15.8%
      (55/349) among women undergoing infertility treatments. Compared with spontaneous
      pregnancies, the crude relative risk for gestational hypertension in pregnancies
      resulting from infertility treatments was 1.9 (95% confidence interval, 1.4-2.6).
      Multivariate adjustment for parity and prepregnancy body mass index resulted in a
      relative risk of 1.6 (1.1-2.1). Further adjustment for multiple pregnancies, or
      restriction of the analyses to singleton pregnancies, moved the relative risk to
      1.3. Each specific infertility procedure or drug was associated with a similarly
      elevated risk, which disappeared after adjustment for multiple gestations.
      Results were similar for preeclampsia. CONCLUSION(S): Pregnancies resulting from
      infertility treatments have a higher incidence of gestational hypertension and
      preeclampsia than do spontaneous conceptions. This increased risk is largely
      explained by the higher frequency of multiple gestations.

PMID- 17449035
TI  - Evaluation of the embryo transfer protocol by a laboratory model of the uterus.
AB  - OBJECTIVE: To investigate the dispersion of transferred matter within a uterine
      laboratory model during and after embryo transfer (ET) as a function of uterine
      position, catheter placement, and injection speed. DESIGN: Experimental setup.
      SETTING: Reproductive bioengineering laboratory. PATIENT(S): N/A INTERVENTION(S):
      N/A MAIN OUTCOME MEASURE(S): Laboratory simulations of ET into a rigid
      transparent uterine model. The catheter was loaded with sequences of liquid and
      air as in the clinical setting. Experiments were conducted for different
      inclinations of the uterine model, various transfer speeds of the catheter load,
      and placement of the catheter tip near and remote from the fundus. RESULT(S):
      Dispersion of the transferred matter depended on the position of sagittal cross
      section of the uterine cavity with respect to the horizon. The air bubbles were
      pulled up by buoyant forces toward the highest point of the cavity (e.g., the
      fundus) and thereby dragged behind them the transferred media with the embryos.
      Placement of the catheter tip near the fundus appeared to transfer the embryos
      into the tube when transfer was performed at fast speeds, possibly leading to
      ectopic pregnancies. CONCLUSION(S): Fundal level of the uterine cavity, location
      of the catheter tip, and transfer speed determine the potential for embryo
      implantation. Adjustment of ET protocol to individual patient anatomy is
      recommended.

PMID- 17449036
TI  - Inducible nitric oxide synthase from bone marrow-derived cells plays a critical
      role in regulating colonic inflammation.
AB  - BACKGROUND & AIMS: Nitric oxide (NO) is an important mediator of intestinal
      inflammation. Inducible NO synthase (iNOS) is the main source of NO in
      inflammation. Because iNOS is ubiquitously expressed, our aim was to determine
      which cellular source(s) of iNOS plays the central role in mediating intestinal
      inflammation. METHODS: Chimeric lines were produced via bone marrow (BM)
      transplantation following irradiation. Colitis was induced with dextran sodium
      sulfate (DSS) or trinitrobenzene sulfonic acid (TNBS). The severity of colitis
      and markers of inflammation were assessed in standard fashion. Leukocyte
      recruitment was assessed by intravital microscopy. RESULTS: The irradiated
      chimeric lines with iNOS-/- BM-derived cells were markedly more resistant to both
      DSS- and TNBS-induced injury. Resistance to DSS-induced colitis was lost when
      wild-type (wt) BM was used to reconstitute iNOS-/- mice. Neutrophils were the
      main source of iNOS in DSS-induced colitis. iNOS-/- chimeric lines had decreased
      colonic macrophage inflammatory protein 1beta and tumor necrosis factor alpha
      expression and increased levels of the protective growth factor, keratinocyte
      growth factor. LPS-mediated leukocyte recruitment was reduced in iNOS-/- mice,
      and there were marked changes in the inflammatory cell infiltrates between the
      chimeric lines with iNOS-/- vs wt BM-derived cells. Furthermore, the lamina
      propria CD4 +ve cells from chimeric lines with iNOS-/- BM-derived cells had
      reduced intracellular cytokine expression. CONCLUSIONS: iNOS produced by BM
      derived cells plays a critical role in mediating the inflammatory response during
      colitis. Cell-specific regulation of iNOS may represent a novel form of therapy
      for patients with inflammatory bowel disease.

PMID- 17449037
TI  - Tracking the evolution of the proenkephalin gene in tetrapods.
AB  - In gnathostomes there is remarkable consistency in the organization of the
      proenkephalin gene. This opioid precursor encodes seven opioid (YGGF) sequences:
      five pentapeptide sequences, a met-enkephalin-7 sequence and a met-enkephalin-8
      sequence. Yet, within vertebrate lineages there can be distinct sets of
      pentapeptide opioids (YGGFM or YGGFL). In the Sarcopterygii, the sixth opioid
      position in lungfishes and anuran amphibian proenkephalin genes encodes a met
      enkephalin (YGGFM) sequence. However, in mammalian proenkephalin there is a leu
      enkephalin (YGGFL) sequence at this position. This study was done to test the
      hypothesis that the presence of the leu-enkephalin sequence in mammals is a
      feature common to amniote vertebrates, but not present in anamniote vertebrates.
      To resolve this issue, proenkephalin cDNAs were cloned from the urodele
      amphibians, Amphiuma means and Necturus maculosus, and two amniote vertebrates,
      the turtle, Chrysemys scripta, and the brown snake, Storeria dekayi. As
      predicted, a met-enkephalin sequence is present at the sixth opioid position in
      urodele amphibians; whereas, a leu-enkephalin sequence is present at this opioid
      site in the reptile proenkephalin sequences. These data are consistent with the
      conclusion that the transition from a met-enkephalin sequence to a leu-enkephalin
      sequence at the sixth opioid position in tetrapod proenkephalins occurred in the
      ancestral proto-reptiles. Phylogenetic analyses, using the Maximum Parsimony and
      Neighbor-Joining algorithms, of the amphibian proenkephalin sequences supported
      the position that anuran and urodele amphibians are a monophyletic assemblage.
      The same analysis of reptile-related proenkephalin sequences, including the
      deduced amino acid sequence of a partially characterized alligator proenkephalin
      cDNA, could not conclusively resolve the phylogeny of the major reptilian orders.

PMID- 17449038
TI  - Plantar shear stress distributions: comparing actual and predicted frictional
      forces at the foot-ground interface.
AB  - Plantar shear stresses are believed to play a major role in diabetic ulceration.
      Due to the lack of commercial devices that can measure plantar shear
      distribution, a number of mathematical models have been developed to predict
      plantar frictional forces. This study assessed the accuracy of these models using
      a custom-built platform capable of measuring plantar stresses simultaneously. A
      total of 48 (38 healthy and 10 diabetic) human subjects (75+/-20 kg, 41+/-20
      years, 32 males, 16 females) were recruited in the study. Plantar force data were
      collected for 2s at 50 Hz. Two models (M1 and M2) reported in the literature by
      different groups were used to predict local shear stresses. Root mean squared
      errors (RMSE) were calculated to compare model data with the actual data,
      focusing on three parameters: location, magnitude and timing of peak shear
      components. RMSE values of estimated peak AP and ML shear locations were 3.1 and
      2.2 cm for M1 and 3.1 and 2.1cm for M2, respectively. Magnitude RMS error values
      for M1 were found to be 86.6 kPa in AP shear and 38.5 kPa in ML shear, whereas
      these values were determined to be 97.8 and 63.5 kPa, respectively by M2. Time to
      peak shear RMSE values averaged 17.2% in terms of the gait duration. In
      conclusion, distribution of plantar shear should be measured rather than
      predicted, particularly if one is interested in the magnitudes of shear
      components.

PMID- 17449039
TI  - Quantification of eicosapentaenoic and docosahexaenoic acid geometrical isomers
      formed during fish oil deodorization by gas-liquid chromatography.
AB  - Long-chain polyunsaturated fatty acids (LC-PUFAs) of the n-3 series and
      especially eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively)
      have important biological properties. The main dietary sources of LC-PUFAs are
      fish and fish oil. Geometrical isomerization is one of the main reactions
      happening during the thermal treatment of polyunsaturated fatty acids. Refined
      fish oils are used to supplement food products in LC-PUFAs and the quality of
      these nutritional ingredients have to be controlled. In the present study, a
      suitable method for the quantification of EPA and DHA geometrical isomers in fish
      oils by gas-liquid chromatography (GC) is presented. A highly polar capillary
      column (CP-Sil 88, 100 m) operating under optimal conditions was used. Method
      selectivity was studied by GC-mass spectrometry. The performance characteristics
      of the quantification method were studied using samples of fish oil deodorized at
      220 degrees C for 3 h. The linearity of the method was assessed by analyzing
      composite samples obtained by mixing fish oil deodorized at 220 degrees C with
      semi-refined fish oil (control). Precision was evaluated by analyzing the same
      samples in triplicate. Results showed that the validated method is suitable to
      quantify low amounts of geometrical (trans) isomers of EPA and DHA in refined
      fish oils. The limits of quantification of the EPA and DHA geometrical isomers
      are 0.16 and 0.56 g/100 g of fish oil, for EPA and DHA, respectively.
      Commercially available LC-PUFA oil samples were evaluated by using the validated
      method. The results show that the oils analyzed contain low amounts (<1% of total
      fatty acids) of geometrical isomers of EPA and DHA.

PMID- 17449040
TI  - Development of a quantitative method for the analysis of total L-ascorbic acid in
      foods by high-performance liquid chromatography.
AB  - A new method has been developed for the determination of total vitamin C in
      foods. The method requires less time than the traditional methodologies and uses
      a radical oxidation of L-ascorbic acid (AA) to obtain dehydro-L-ascorbic acid
      (DHAA) by means of a peroxyl radical generated in situ by thermal decomposition
      of an azo-compound, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). The
      dehydro-L-ascorbic acid is condensed with benzene-1,2-diamine (o
      phenylenediamine, OPDA) to form its highly fluorescent quinoxaline derivative, 3
      (1,2-dihydroxyethyl)furo[3,4-b]quinoxaline-1-one (DFQ), which is then separated
      on a C(18) column eluted with a mobile phase of 80 mM phosphate buffer and
      methanol at pH=7.8 and detected fluorometrically at lambda(ex)=355 nm and
      lambda(em)=425 nm. The reaction conditions for the complete conversion of AA to
      DFQ were 56 degrees C, 36 min and a mumol AAPH/AA ratio of 60. The sample,
      extracted with an aqueous metaphosphoric acid solution, was analyzed after being
      filtered through a 0.45 microm membrane. The method has shown good repeatability,
      sensitivity and accuracy compared to the results obtained with the reference
      method. The response of the detection system was linear within a range of 0.5-8.0
      microg/mL with a correlation coefficient of 0.9997. The limit of detection was
      0.27 microg/mL and the limit of quantification was 0.83 microg/mL. The AA
      contents of some selected foods were analyzed.

PMID- 17449041
TI  - Detection of glucocorticoid residues in pig liver by high-performance liquid
      chromatography with on-line electrogenerated [Cu(HIO6)2](5-)--luminol
      chemiluminescence detection.
AB  - A novel method was developed for the simultaneous determination of glucocorticoid
      residues such as triamcinolone (TR), prednisolone (PR), hydrocortisone (HC),
      cortisone (CO), methylprednisolone (MP), dexamethasone (DE) and triamcinolone
      acetonide (TA) by high-performance liquid chromatography (HPLC) coupled with
      chemiluminescence (CL) detection. The procedure was based on the enhancement
      effect of glucocorticoids on the chemiluminescence reaction between luminol and
      the complex of trivalent copper and periodate ([Cu(HIO6)2]5-), which was on-line
      electrogenerated by constant current electrolysis. The HPLC separation used a
      Nucleosil RP-C18 column (250 mmx4.6 mm i.d., 5 microm, pore size, 100 A) with a
      mobile phase consisting of acetonitrile and 1.0 mmol L(-1) ammonium acetate (pH
      6.8, 40:60,v/v) at a flow rate of 0.8 mL min(-1). The effects of several
      parameters on the HPLC resolution and CL emission were studied systematically.
      Liver samples were hydrolyzed with Helix pomatia juice followed by a solid-phase
      extraction procedure. Under optimum conditions, the limits of detection (LOD) at
      a signal-to-noise of 3 ranged from 0.08 to 1.0 ng g(-1) and the limits of
      quantification (LOQ) at a signal-to-noise of 10 ranged from 0.27 to 3.33 ng g(-1)
      for seven glucocorticoids. The relative standard deviations (RSD) of intra- and
      inter-day precision were below 6.8%. The average recoveries for glucocorticoids
      (spiked at the levels of 5-50 ng g(-1)) in pig liver ranged from 88 to 106%, and
      the relative standard deviations of the quantitative results were from 2.0 to
      6.9%. The proposed method had been successfully applied to the determination of
      glucocorticoid residues in pig liver.

PMID- 17449042
TI  - Elution of tightly bound solutes from concanavalin A Sepharose. Factors affecting
      the desorption of cottonmouth venom glycoproteins.
AB  - Some glycoproteins bind so tightly to concanavalin A Sepharose that common
      desorption techniques are ineffective, so a systematic exploration of factors
      affecting desorption of cottonmouth venom glycoproteins was undertaken.
      Glycoprotein desorption is greatly improved by introducing up to four pauses of 5
      10 min duration into the elution step. Eluent concentrations above 250 mM
      methylglucoside or 500 mM methyl-mannoside reduced glycoprotein desorption.
      Eluent NaCl diminished glycoprotein desorption. Most venom glycoproteins desorb
      more readily as pH diminishes from 6.0 to 4.0, but phosphodiesterase shows the
      opposite pattern. Eluents recommended by the supplier for desorbing solutes or
      for column cleaning were ineffectual.

PMID- 17449043
TI  - Supercritical fluid chromatography of metoprolol and analogues on aminopropyl and
      ethylpyridine silica without any additives.
AB  - Metoprolol and a number of related amino alcohols and similar analytes have been
      chromatographed on aminopropyl (APS) and ethylpyridine (EPS) silica columns. The
      mobile phase was carbon dioxide with methanol as modifier and no amine additive
      was present. Optimal isocratic conditions for the selectivity were evaluated
      based on experiments using design of experiments. A central composite
      circumscribed model for each column was used. Factors were column temperature,
      back-pressure and % (v/v) of modifier. The responses were retention and
      selectivity versus metoprolol. The % of modifier mainly controlled the retention
      on both columns but pressure and temperature could also be important for
      optimizing the selectivity between the amino alcohols. The compounds could be
      divided into four and five groups on both columns, with respect to the
      selectivity. Furthermore, on the aminopropyl silica the analytes were more spread
      out whereas on the ethylpyridine silica, due to its aromaticity, retention and
      selectivity were closer. For optimal conditions the column temperature and back
      pressure should be high and the modifier concentration low. A comparison of the
      selectivity using optimized conditions show a few switches of retention order
      between the two columns. On aminopropyl silica an aldehyde failed to be eluted
      owing to Schiff-base formation. Peak symmetry and column efficiency were briefly
      studied for some structurally close analogues. This revealed some activity from
      the columns that affected analytes that had less protected amino groups, a methyl
      group instead of isopropyl. The tailing was more marked with the ethylpyridine
      column even with the more bulky alkyl substituents. Plate number N was a better
      measure than the asymmetry factor since some analyte peaks broadened without
      serious deterioration of symmetry compared to homologues.

PMID- 17449044
TI  - High-performance liquid chromatographic fingerprint analysis for different
      origins of sea buckthorn berries.
AB  - Using high-performance liquid chromatography (HPLC), a chemical fingerprint
      method was developed for investigating and demonstrating the variance of
      flavonoids among different origins of sea buckthorn berries. Thirty-four samples
      were analyzed including 15 RS (Hippophae rhamnoides ssp. sinensis) samples, 7 RY
      (H. rhamnoindes ssp. yunnanensis) samples, 5 RW (H. rhamnoides ssp. wolongensis)
      samples, 4 NS (H. neurocarpa ssp. stellatopilosa) samples and 3 TI (H. tibetana)
      samples. In the HPLC chromatograms, 12 compounds were identified as flavonoids,
      including quercetin 3-O-sophoroside-7-rhamnoside, kaempferol 3-O-sophoroside-7-O
      rhamnoside, isorhamnetin 3-O-sophoroside-7-O-rhamnoside, isorhamnetin 3-O
      glucoside-7-O-rhamnoside, quercetin 3-O-rutinoside, quercetin 3-O-glucoside,
      isorhamnetin 3-O-rutinoside, isorhamnetin 3-O-glucoside, quercetin, kaempferol 7
      O-rhamnoside, kaempferol and isorhamnetin. Both correlation coefficient of
      similarity in chromatograms and relative peak areas of characteristic compounds
      were calculated for quantitative expression of the HPLC fingerprints. Our results
      revealed that the chromatographic fingerprint combining similarity evaluation
      could efficiently identify and distinguish sea buckthorn berries from different
      species. However, no obvious difference between RS and RY suggested that the two
      subspecies might have very close relationship in terms of chemotaxonomy. The
      established method was considered to be suitable for fingerprint analysis to
      check the genuine origin and control the quality of sea buckthorn berries and
      extracts.

PMID- 17449045
TI  - Arginine improves protein elution in hydrophobic interaction chromatography. The
      cases of human interleukin-6 and activin-A.
AB  - The effects of arginine on protein binding and elution in hydrophobic interaction
      chromatography (HIC) were examined using recombinant human interleukin-6 (IL-6)
      and activin-A. Binding of IL-6 in the presence of ammonium sulfate (AS) was
      tested using low- and high-substituted phenyl-sepharose. While inclusion of
      arginine during loading of IL-6 resulted in incomplete binding to the low
      substituted phenyl-sepharose, binding was complete to the high-substituted phenyl
      sepharose. Arginine facilitated elution of IL-6 from both columns. These results
      demonstrate that arginine weakens hydrophobic interactions between IL-6 and the
      phenyl-sepharose. More drastic results were obtained using activin-A, which
      showed undetectable recovery from phenyl-sepharose. Although no apparent elution
      of activin-A was observed from butyl-sepharose in aqueous buffer alone, the
      addition of arginine to the buffer resulted in partial elution recovery and,
      together with ethanol, resulted in greatly improved recovery of the protein. Two
      arginine derivatives, acetylarginine and agmatine, were also effective. These
      results show that arginine improves protein elution in HIC.

PMID- 17449046
TI  - Adsorption behavior of a teicoplanin aglycone bonded stationary phase under harsh
      overload conditions.
AB  - Silica-bonded teicoplanin aglycone allows enantioseparation of amino acids by
      reversed-phase liquid chromatography with a low organic solvent content. However,
      a reversible change in the adsorption behavior leading to a retention time shift
      (RTS) was observed when a preparative scale column was treated with harsh
      preparative chromatography-like conditions between finite-injection HPLC runs
      conducted under exactly the same conditions. This behavior was observed for all
      five investigated aliphatic and aromatic amino acids. In all cases, the retention
      times were prolonged after the overload conditions and the RTS was more
      pronounced for the later eluting d-enantiomer. We defined a standardized method
      for measuring the RTS and performed a systematic investigation on the influence
      of experimental conditions (type and concentration of pH modifier and organic
      modifier, temperature, pH) on the RTS. In this way a solvent composition--90/10
      50 mM NH4Ac pH 5.8/MeOH--was identified that yielded no observable shift in
      retention time after overload conditions for both enantiomers. In order to treat
      the observed phenomenon on a mechanistic level, we applied band profile analysis
      based on the stochastic theory of chromatography and identified two different
      enantioselective sites. When the band profile analysis was performed on elution
      profiles obtained from runs with prolonged retention time after harsh overload
      conditions, the retention time shift could be attributed to both differentiable
      types of adsorption sites. One site was found to make both, enantioselective and
      non-selective contributions.

PMID- 17449047
TI  - Influence of different polymerisation parameters on the separation efficiency of
      monolithic poly(phenyl acrylate-co-1,4-phenylene diacrylate) capillary columns.
AB  - Monolithic poly(phenyl acrylate-co-1,4-phenylene diacrylate) (PA/PDA) capillary
      columns were prepared in the confines of 200 microm I.D. fused silica capillaries
      by thermally initiated free radical copolymerisation of phenyl acrylate (PA) and
      1,4-phenylene diacrylate (PDA) in the presence of alpha,alpha'
      azoisobutyronitrile (AIBN). Variation of polymerisation parameters in terms of
      total monomer to porogen ratio, nature of the pore-forming agent and
      polymerisation temperature is shown to have a significant impact on the porous
      properties of the supports, which was proven by inverse size-exclusion
      chromatography (ISEC). Monoliths of significantly different porosity (total
      porosity accessible to the mobile phase (epsilonT)=0.66-0.71, volume fraction of
      pores (epsilonP)=0.15-0.24) and hence permeability could easily be prepared. The
      chromatographic efficiency of the PA/PDA monoliths regarding protein and
      oligonucleotide separation was studied. A correlation between porosity, retention
      behaviour and efficiency was derived from the obtained separations. In addition
      to chromatographic evaluation, pressure drop versus flow rate measurements
      confirmed mechanical stability. Swelling propensity (SP) factors of 0.47-0.87,
      moreover, indicated a high degree of crosslinking.

PMID- 17449048
TI  - Optimization and validation of a methodology based on solvent extraction and
      liquid chromatography for the simultaneous determination of several polyphenolic
      families in fruit juices.
AB  - A solvent extraction procedure of freeze-dried aliquots followed by the analysis
      of phenolic compounds by reversed-phase high-performance liquid chromatography
      (RP-HPLC) with photodiode array detection (DAD) has been developed for the
      analysis of polyphenolic compounds in fruit juices. This methodology is focussed
      on the characterization of fruit juices, mainly for quality control purposes. The
      effects of experimental variables, such as solvent composition and volume and
      time and temperature on extraction, have been studied. A unique gradient program
      for the separation of several phenolic classes (hydroquinones, hydroxybenzoic
      acids, flavan-3-oles, hydroxycinnamic acids, coumarins, flavanones, flavones,
      dihydrochalcones and flavonols) has been optimized, using standards of 55
      commercially available phenolic compounds present in fruits, as well as
      representative real extracts from fruit juices. All phenolic compounds showed a
      high repeatability within-day (n=5) and between days (n=3) in peak area (RSD<8%)
      and excellent stability of their retention times. High precision was also
      observed in calibration slopes (RSD<8%). Detection limits ranged between 0.005
      and 0.03 microg/mL for the different detected polyphenols. Complete recoveries
      (98-100%) were obtained for the majority of the phenolic structures of all
      representative phenolic families present in fruits. The method was successfully
      employed to measure diverse phenolic families in juices from 18 different fruits
      and consequently could be used for evaluate the quality of fruit juices.

PMID- 17449049
TI  - Configurations and calibration methods for passive sampling techniques.
AB  - Passive sampling technology has developed very quickly in the past 15 years, and
      is widely used for the monitoring of pollutants in different environments. The
      design and quantification of passive sampling devices require an appropriate
      calibration method. Current calibration methods that exist for passive sampling,
      including equilibrium extraction, linear uptake, and kinetic calibration, are
      presented in this review. A number of state-of-the-art passive sampling devices
      that can be used for aqueous and air monitoring are introduced according to their
      calibration methods.

PMID- 17449050
TI  - Continuous full filling capillary electrochromatography: nanoparticle synthesis
      and evaluation.
AB  - Reversed phase continuous full filling capillary electrochromatography with
      electrospray ionisation mass spectrometric detection was performed with highly
      sulphated poly[styrene-co-(lauryl methacrylate)-co-(divinylbenzene)]
      nanoparticles. The nanoparticles that contained a hydrophobic core and a
      hydrophilic surface were prepared in a one step synthesis using soap free
      emulsion polymerisation. By changing the concentration of monomers, the
      polymerisation temperature, and the polarity of the dispersive phase, the size of
      the nanoparticles could be controlled. With the optimised conditions,
      nanoparticles with an average size of 157 nm were obtained. These nanoparticles
      were dispersed in the background electrolyte and used for reversed phase
      continuous full filling. An orthogonal electrospray ionisation interface was used
      to separate the eluting nanoparticles from the eluting analytes prior to mass
      spectrometry detection. Compared to previous studies on reversed phase continuous
      full filling, the retention, the separation efficiency, and the resolution of a
      homologous series of dialkyl phthalates were greatly improved.

PMID- 17449051
TI  - Rapid and high throughput separation technologies--steady state recycling and
      supercritical fluid chromatography for chiral resolution of pharmaceutical
      intermediates.
AB  - The SSR and SFC techniques were used for the enantiomeric resolution of three
      pharmaceutical intermediates at various sample scales. The separation conditions,
      the sample purities and yields, the productivities and the solvent consumptions
      were discussed in three case studies in this paper. In case (I), the SSR process
      was used for a low selectivity resolution of 2.0 kg of pharmaceutical
      intermediate. By using this separation process, a productivity of 750 g
      racemate/kg stationary phase/day was achieved, while solvent usage was minimized
      ( approximately 200 l/kg racemate). Case (II) pertained to the effectiveness of
      the SSR process. Productivity using SSR techniques increased by a factor of 4.5,
      while solvent usage decreased by a factor of 4.1 when compared to the
      productivity and solvent usage of batch HPLC. Case (III) compared SFC
      purification to HPLC purification. The SFC process was more effective in terms of
      an increase in productivity and a reduction in solvent usage. Based on these
      results, it appears that SSR and SFC are very useful choices at the early stage
      of the drug development for a high throughput and a rapid turn around of samples.

PMID- 17449052
TI  - Passive extraction and clean-up of phenoxy acid herbicides in samples from a
      groundwater plume using hollow fiber supported liquid membranes.
AB  - Hollow fiber supported liquid membranes were applied for the passive extraction
      of phenoxy acid herbicides from water samples. Polypropylene hollow fiber
      membranes (240 microm i.d., 30 microm wall thickness, 0.05 microm pore size, 30
      cm length) were impregnated with 2.0% tri-n-octylphosphine oxide (TOPO) in di-n
      hexyl ether in the pores of the fiber wall to form a liquid membrane. They were
      then filled with basic solution in the lumen as acceptor and finally placed into
      the sample (donor). Complete extraction of phenoxy acid herbicides including 2,4
      D, MCPA, dichlorprop, and mecoprop from an acidified sample (4 mL, adjusted to pH
      1.5 with HCl) into basic acceptor (10 microL of 0.2M NaOH) was achieved after 4 h
      of shaking (100 rpm) resulting in an enrichment factor of 400 times. The acceptor
      was then neutralized by addition of HCl and injected into a HPLC system for the
      determination of the phenoxy acid herbicides. Environmentally relevant salinity
      (0-3.5% NaCl) and dissolved organic matter (0-25 mg/L of dissolved organic
      carbon) had no significant effect on the extraction. The method provided
      extraction efficiencies of more than 91%, detection limits of 0.3-0.6 microg/L,
      and combined extraction and clean up in one single step. This procedure was
      applied to determine aqueous concentrations of phenoxy acid herbicides in
      groundwater samples collected from an old dumping site (Cheminova, Denmark) with
      detected concentrations up to 5800 microg/L. Although the samples were very dirty
      with large amounts of suspended particles, non-aqueous phase liquids (NAPLs) and
      dissolved organic matters, good spike recoveries (80-126%) were obtained for 10
      of the 11 samples.

PMID- 17449053
TI  - Macroporous molecularly imprinted polymer/cryogel composite systems for the
      removal of endocrine disrupting trace contaminants.
AB  - A new concept for the preparation of selective sorbents with high flow path
      properties is presented by embedding molecularly imprinted polymers (MIPs) into
      various macroporous gels (MGs). A MIP was first synthetized with 17beta-estradiol
      (E2) as template for the selective adsorption of this endocrine disrupter. The
      composite macroporous gel/MIP (MG/MIP) monoliths were then prepared at subzero
      temperatures. Complete recovery of E2 from a 2 microg/L aqueous solution was
      achieved using the polyvinyl alcohol (PVA) MG/MIP monoliths whereas only 49-74%
      was removed with non-imprinted polymers (when no template was used). The PVA
      MG/MIP monolith columns were operated at almost 10 times higher flow rate (50
      mL/min) compared to the MIP columns with operation flow rate of 1-5 mL/min. The
      possibility for processing the particulate containing wastewater effluents at
      high flow rates with selectivity on E2 removal, as well as the easy preparation
      of the monoliths, make the macroporous MG/MIP systems attractive and robust
      sorbents for the clean up of water from endocrine disrupting trace contaminants.

PMID- 17449054
TI  - Influence of surface treatments on micropore structure and hydrogen adsorption
      behavior of nanoporous carbons.
AB  - The scope of this work was to control the pore sizes of porous carbons by various
      surface treatments and to investigate the relation between pore structures and
      hydrogen adsorption capacity. The effects of various surface treatments (i.e.,
      gas-phase ozone, anodic oxidation, fluorination, and oxygen plasma) on the
      micropore structures of porous carbons were investigated by N(2)/77 K isothermal
      adsorption. The hydrogen adsorption capacity was measured by H(2) isothermal
      adsorption at 77 K. In the result, the specific surface area and micropore volume
      of all of the treated samples were slightly decreased due to the micropore
      filling or pore collapsing behaviors. It was also found that in F(2)-treated
      carbons the center of the pore size distribution was shifted to left side,
      meaning that the average size of the micropores decreased. The F(2)- and plasma
      treated samples showed higher hydrogen storage capacities than did the other
      samples, the F(2)-treated one being the best, indicating that the micropore size
      of the porous carbons played a key role in the hydrogen adsorption at 77 K.

PMID- 17449055
TI  - Emulsions stabilised by food colloid particles: role of particle adsorption and
      wettability at the liquid interface.
AB  - We study the effect of the particle wettability on the preferred type of emulsion
      stabilised solely by food colloid particles. We present results obtained with the
      recently developed gel trapping technique (GTT) for characterisation of
      wettability and surface structuring of individual food colloid particles adsorbed
      at air-water and oil-water interfaces. This method allows us to replicate a
      particle monolayer onto the surface of polydimethylsiloxane (PDMS) without
      altering the position of the particles. By observing the polymer surface with
      scanning electron microscopy (SEM), we are able to determine the contact angle of
      the individual particles at the initial liquid interface. We demonstrate that the
      GTT can be applied to fat crystal particles, calcium carbonate particles coated
      with stearic acid and spray-dried soy protein/calcium phosphate particles at air
      water and oil-water interfaces. Subsequently, we prepare emulsions of decane and
      water stabilised by the same food colloid particles and correlate the wettability
      data obtained for these particles to the preferred type of emulsions they
      stabilise.

PMID- 17449056
TI  - Effective adsorption energy distribution function as a new mean-field
      characteristic of surface heterogeneity in adsorption systems with lateral
      interactions.
AB  - Recent papers [W. Piasecki, Langmuir 22 (2006) 6761; P. Zarzycki, Langmuir 22
      (2006) 11234; P. Zarzycki, J. Colloid Interface Sci. 306 (2007) 328] showed that
      the distinction between surface heterogeneity and effects of electrostatic
      interactions becomes problematic for metal oxide/electrolyte systems. This
      observation suggests that both mentioned factors can be combined into one
      ("effective" energy). Hence, the effective adsorption energy distribution
      function (EAEDF) with the Langmuir isotherm can be used in the framework of
      integral adsorption isotherm (IAI) instead of the classical adsorption energy
      distribution function (AEDF) with the Fowler-Guggenheim isotherm. The histogram
      method was used to obtain the effective distributions from the grand canonical
      Monte Carlo simulations of H+ ion adsorption. The new approach (IAI/EAEDF) gives
      a much better description of the heterogeneous metal oxide/electrolyte interface
      than IAI/AEDF. Moreover, reduced quantities are introduced in order to compare
      different metal oxide/electrolyte systems in a convenient way.

PMID- 17449057
TI  - Micellar induced regioselectivity in the two-step consecutive reaction of SO3(2-)
      with Br-(CH2CH2)n-Br (n=2-5).
AB  - High field (800 MHz) (1)H NMR was used to monitor the two-step consecutive
      reaction of excess SO(3)(2-) with symmetrical bifunctional alpha,omega
      dibromoalkanes with butane (DBB), hexane (DBH), octane (DBO), and decane (DBD)
      chains in CTAB micelles at 25 degrees C. The first-order rate constant for the
      first substitution step for DBB and DBH is about 5 times faster than for the
      second, but the kinetics for DBO and DBD were not cleanly first-order. After 40
      min, the solution contained about 80% of the intermediate bromoalkanesulfonate
      from DBB and DBH and the remainder is alkanedisulfonate and unreacted starting
      material. The same reactions were carried out in homogeneous MeOH/D(2)O solutions
      at 50 degrees C. The rate constants for all four alpha,omega-dibromoalkanes were
      first-order throughout the time course of the reaction and the same within +/
      10%. However, because micellar solutions are organized on the nanoscale and bring
      together lipophilic and hydrophilic reactants into a small reaction volume at the
      micellar interface, they speed this substitution reaction considerably compared
      to reaction in MeOH/D(2)O. The CTAB micelles also induce a significant
      regioselectivity in product formation by speeding the first step of the
      consecutive reaction more than the second. The results are consistent with the
      bromoalkanesulfonate intermediates having a radial orientation within the
      micelles with the -CH(2)SO(3)(-) group in the interfacial region and the -CH(2)Br
      group directed into the micellar core such that the concentration of -CH(2)Br
      groups in the reactive zone, i.e., the micellar interface, is significantly
      reduced. These results provide the first example of self-assembled surfactant
      system altering the relative rates of the reaction steps of a consecutive
      reaction and, in doing so, enhancing monosubstitution of a symmetrically
      disubstituted species.

PMID- 17449058
TI  - The Bombyx mori sex pheromone biosynthetic pathway is not mediated by cAMP.
AB  - In most moths, sex pheromone production is regulated by pheromone biosynthesis
      activating neuropeptide (PBAN). How the extracellular PBAN signal is turned into
      a biological response has been the focus of numerous studies. In the classical
      scheme of signal transduction, activated G proteins relay the extracellular
      signal to downstream effector molecules such as calcium channels and adenylyl
      cyclase. The role of calcium in PBAN signaling has been clearly demonstrated, but
      the possible involvement of cAMP is not as straightforward. While cAMP has been
      shown to be necessary for PBAN signaling in most heliothine species, there has
      been no definitive demonstration of its role in Bombyx mori. To address this
      question, we used degenerate RT-PCR to clone two Gs subunits, designated P50Gs1
      and P50Gs2, from B. mori pheromone gland (PG) cDNAs. The two Gs proteins were
      expressed in all tissues examined and were not up-regulated in accordance with
      adult eclosion. Even though two bands corresponding to the approximate molecular
      weights of P50Gs1 and P50Gs2 were detected in PG homogenates, the Gs antagonist,
      NF449, had no effect on sex pheromone production. Furthermore, no changes in the
      intracellular cAMP levels were detected following PBAN stimulation.

PMID- 17449059
TI  - Structural basis for a high affinity inhibitor bound to protein kinase MK2.
AB  - The Ser/Thr protein kinase MAPKAP kinase 2 (MK2) plays a crucial role in
      inflammation. We determined the structure of the kinase domain of MK2 in complex
      with a low molecular mass inhibitor in two different crystal forms, obtained from
      soaking and co-crystallization. To our knowledge, these are the first structures
      of MK2 showing the binding mode of an inhibitor with high binding affinity (IC50
      8.5 nM). The two crystal forms revealed conformational flexibility in the binding
      site and extend the experimental basis for rational drug design. Crystal form-1
      contained one MK2 molecule per asymmetric unit. Form-2 contained 12 molecules,
      which arrange into two different types of MK2 trimers. One of them may serve as a
      model for an intermediate state during substrate phosphorylation, as each MK2
      monomer places its activation segment into the substrate peptide binding groove
      of the trimer neighbor.

PMID- 17449060
TI  - Inter-hemispheric asymmetry of motor corticospinal excitability in major
      depression studied by transcranial magnetic stimulation.
AB  - BACKGROUND: Imaging and electroencephalographic studies have reported inter
      hemispheric asymmetries in frontal cortical regions associated with depression.
      This study aimed at comparing motor corticospinal excitability assessed by
      methods of transcranial magnetic stimulation (TMS) between the right and left
      hemispheres in patients with major depression and healthy controls. METHOD:
      Patients with major depression (n=35) and healthy controls (n=35) underwent a
      bilateral study of various motor corticospinal excitability parameters, including
      rest motor threshold (RMT), corticospinal silent period (CSP) duration and intra
      cortical inhibition (ICI) and facilitation (ICF). Indexes of asymmetry were
      calculated, and the relationships between excitability parameters and clinical
      scores of depression were statistically analyzed. RESULTS: Depressed patients
      showed a reduced excitability of both excitatory (RMT, ICF) and inhibitory (CSP,
      ICI) processes in the left hemisphere, compared to the right hemisphere and to
      healthy controls. CONCLUSION: The present results confirmed the existence of
      inter-hemispheric asymmetries in frontal cortex activities of depressed patients
      in favor of a left-sided reduced excitability. This neurophysiological approach
      may help to guide repetitive TMS procedures in the treatment of depressive
      disorders.

PMID- 17449061
TI  - Individual differences predict susceptibility to conditioned fear arising from
      psychosocial trauma.
AB  - BACKGROUND: Classical Pavlovian fear conditioning has been widely used in
      preclinical studies to gain insights into anxiety-related disorders. In this
      study we examined whether pre-existing behavioral differences, and/or behavioral
      differences displayed during fear induction, predict the severity of the
      conditioned fear response that can develop after an episode of psychosocial
      conflict. METHODS: Prior to conditioning, male rats (intruders) were behaviorally
      assessed using the novel environment exploration and defensive burying tests.
      These animals were subsequently placed in the territory of an older male
      (resident) that invariably attacked the intruder. RESULTS: Upon return to this
      territory 24 h later, intruders moved less than controls and produced more
      distress vocalizations, indicating conditioned fear to context. Additionally,
      analyses revealed that both pre-existing behavioral differences, and the animal's
      response during social conflict, predicted the magnitude of the subsequent
      conditioned fear response. Specifically, animals that engaged in higher levels of
      novel environment exploration, that exhibited a greater number of defensive
      burying behaviors, and that demonstrated higher levels of fighting and guarding
      during social conflict, displayed less evidence of conditioned fear. CONCLUSION:
      These findings show that the behavioral variability existent within a normal
      outbred population can predict the magnitude of the conditioned fear response.

PMID- 17449062
TI  - Cortico-subcortical distribution of microbleeds is different between hypertension
      and cerebral amyloid angiopathy.
AB  - BACKGROUND: The cerebral distribution of microbleeds in cerebral amyloid
      angiopathy (CAA) is quite different from that in hypertension, i.e., microbleeds
      in central gray matters are frequently found in patients with advanced
      hypertension (aHT), but not in patients with CAA. Distributions within the
      cortico-subcortical (CSC) area have not been compared between the diseases, and
      remain poorly understood. OBJECTIVES: We hypothesized that distributions of
      microbleeds differ in aHT and CAA even in the CSC area. METHODS: Out of a
      consecutive series of patients with intracerebral hemorrhage who underwent brain
      MRI (n=181), we selected typical aHT and CAA patients by inclusion criteria.
      Microbleeds in the CSC area were localized according to anatomical divisions and
      vascular territories. Numbers of microbleeds in these areas were counted and
      statistically compared. RESULTS: A total of 52 hemispheres (aHT, n=32; CAA, n=20)
      were analyzed. The number of CSC microbleeds was higher in the CAA group (47.6+/
      56.8) than in the aHT group (17.4+/-27.4; p=0.01). The microbleeds showed a
      significant predilection for the temporo-occipital lobes in the aHT group, but
      for the parietal lobe in the CAA group. The most involved vascular territory was
      middle cerebral artery territory in both groups, but the lesion number in
      anterior cerebral artery territory was relatively high in the CAA group.
      CONCLUSIONS: In this study sample, aHT and CAA show different topographical
      microbleeds distributions, even in the CSC area. Our results suggest that the CSC
      microbleeds may reflect different pathophysiological mechanisms between aHT and
      CAA.

PMID- 17449063
TI  - Intravenous immunoglobulin in MS: promise or failure?
AB  - There is an established role for intravenous immunoglobulin (IVIG) in the
      treatment of certain neurologic autoimmune disorders which affect the peripheral
      nervous system and a variety of immunomodulatory properties of IVIG have been
      proposed. This prompted an intense research into the efficacy of IVIG in central
      nervous system autoimmune disorders and until now several well-controlled
      clinical trials have been performed in different stages and phenotypes of
      multiple sclerosis (MS). The results were mixed. Speculations that IVIG might be
      able to reverse fixed neurologic deficits from MS could not be confirmed. Adding
      IVIG to the conventional treatment of MS relapses with high-dose IVMP also did
      not provide any additional benefits. Similarly, trials failed to establish a role
      for IVIG in the treatment of secondary or primary progressive MS. Most consistent
      beneficial results with a reduction of relapse rates and a slowing of disability
      have been obtained in relapsing-remitting MS including clinically isolated
      syndromes although a most recent study did not confirm a reduction of disease
      activity based on clinical and MRI findings. Trial results also suggest that IVIG
      might serve to suppress an increased recurrence of relapses immediately after
      delivery. Consequently, IVIG treatment may be considered as second line option
      for these indications although there is still uncertainty regarding the actual
      mechanism(s) of action and optimal dosage of this treatment.

PMID- 17449064
TI  - Thalidomide inhibits pentylenetetrazole-induced seizures.
AB  - Thalidomide was originally synthesized and tested as a sedative, hypnotic and
      antiemetic; however, after its teratogenicity was noted its use for treatment of
      neurological and psychiatric disorders was abandoned. We studied the potential
      anticonvulsant effect of thalidomide: Different doses of thalidomide were tested
      against seizures induced by 50 mg/kg or 70 mg/kg of pentylenetetrazole (PTZ); the
      anticonvulsant effect of thalidomide was also compared with that of valproic
      acid. Seizures and latency time were individually recorded. Thalidomide in low
      doses (5-10 mg/kg) prevented seizures in all animals treated with 50 mg/kg PTZ;
      also, in a dose-dependent manner thalidomide inhibited seizures in rats exposed
      to a high dose of PTZ (70 mg/kg); thalidomide exhibited an anticonvulsant
      activity similar to that of valproic acid. Thalidomide is an effective
      anticonvulsant, and further studies on this potential antiepileptic substance
      seem warranted.

PMID- 17449065
TI  - Small molecule intercalation with double stranded DNA: implications for normal
      gene regulation and for predicting the biological efficacy and genotoxicity of
      drugs and other chemicals.
AB  - The binding of small molecules to double stranded DNA including intercalation
      between base pairs has been a topic of research for over 40 years. For the most
      part, however, intercalation has been of marginal interest given the prevailing
      notion that binding of small molecules to protein receptors is largely
      responsible for governing biological function. This picture is now changing with
      the discovery of nuclear enzymes, e.g. topoisomerases that modulate intercalation
      of various compounds including certain antitumor drugs and genotoxins. While
      intercalators are classically flat, aromatic structures that can easily insert
      between base pairs, our laboratories reported in 1977 that a number of
      biologically active compounds with greater molecular thickness, e.g. steroid
      hormones, could fit stereospecifically between base pairs. The hypothesis was
      advanced that intercalation was a salient feature of the action of gene
      regulatory molecules. Two parallel lines of research were pursued: (1)
      development of technology to employ intercalation in the design of safe and
      effective chemicals, e.g. pharmaceuticals, nutraceuticals, agricultural
      chemicals; (2) exploration of intercalation in the mode of action of nuclear
      receptor proteins. Computer modeling demonstrated that degree of fit of certain
      small molecules into DNA intercalation sites correlated with degree of biological
      activity but not with strength of receptor binding. These findings led to
      computational tools including pharmacophores and search engines to design new
      drug candidates by predicting desirable and undesirable activities. The specific
      sequences in DNA into which ligands best intercalated were later found in the
      consensus sequences of genes activated by nuclear receptors implying
      intercalation was central to their mode of action. Recently, the orientation of
      ligands bound to nuclear receptors was found to match closely the spatial
      locations of ligands derived from intercalation into unwound gene sequences
      suggesting that nuclear receptors may be guiding ligands to DNA with remarkable
      precision. Based upon multiple lines of experimental evidence, we suggest that
      intercalation in double stranded DNA is a ubiquitous, natural process and a
      salient feature of the regulation of genes. If double stranded DNA is proven to
      be the ultimate target of genomic drug action, intercalation will emerge as a
      cornerstone of the future discovery of safe and effective pharmaceuticals.

PMID- 17449066
TI  - Neuroprotective effects of the beta-carboline abecarnil studied in cultured
      cortical neurons and organotypic retinal cultures.
AB  - Presently there is no neuroprotective pharmacological treatment of proven
      clinical safety and efficacy available. The purpose of this study was to
      investigate whether the beta-carboline, abecarnil (Abe), which has already passed
      clinical phase III trials in patients with anxiety disorders, is neuroprotective
      in in vitro models of cerebral ischemia or excitotoxicity. Abe (100 nM) protected
      cultured cortical neurons when applied 20 min before or 20 min after combined
      oxygen glucose deprivation (OGD). Furthermore, cultured cortical neurons were
      protected from NMDA excitotoxicity when Abe (100 nM) was administered 20 min
      before or concurrent with 100 microM NMDA. In contrast, in adult rat organotypic
      retinal cultures, Abe failed to protect retinal ganglion cells (RGCs) against
      glutamate (Glu) excitotoxicity. Thus, although our data demonstrate that Abe is a
      potential neuroprotectant in cultured neurons, the lack of effect in an
      organotypical model of Glu toxicity indicates that further study is required
      before Abe might be considered for human neuroprotection trials.

PMID- 17449067
TI  - NMDA inhibitors cause apoptosis of pyramidal neurons in mature piriform cortex:
      evidence for a nitric oxide-mediated effect involving inhibitory interneurons.
AB  - Pyramidal relay neurons in limbic cortex are vulnerable to denervation lesions,
      i.e. pyramidal neurons in layer IIalpha of piriform cortex undergo transsynaptic
      apoptosis after lesions that interrupt their inputs from the olfactory bulb. We
      have previously established the role of inhibitory interneurons in elaborating
      signals that lead to the apoptosis of projection neurons in these lesion models,
      i.e. the upregulation of neuronal NOS and release of nitric oxide. Thus, we have
      proposed that cortical interneurons play an essential role in transducing injury
      to degenerative effects for nearby pyramidal neurons. In the present study, we
      extend the previous findings to a toxic model of degeneration of pyramidal
      neurons in the adult paralimbic cortex, i.e. after exposure to the NMDA channel
      blocker MK801. Our findings indicate that treatment of adult rats with MK801 in
      doses previously found to cause alterations in pyramidal neurons of the
      retrosplenial cortex (5mg/kg) results in an active caspase 3 (+),
      ultrastructurally apoptotic type of cell death involving the same projection
      neurons of layer IIalpha that are also vulnerable to bulbotomy lesions.
      Interneurons of layer I are induced by MK801 treatment to higher levels of nNOS
      expression and the selective nNOS inhibitor BRNI ameliorates pyramidal cell
      apoptosis caused by MK801. Our results indicate that certain pyramidal neurons in
      piriform cortex are very sensitive to NMDA blockade as they are to disconnection
      from modality-specific afferents and that inhibitory interneurons play
      significant roles in mediating various types of pro-apoptotic insults to cortical
      projection neurons via nNOS/NO signaling.

PMID- 17449069
TI  - Left frontal eye field remembers "where" but not "what".
AB  - Short-term memory of basic stimulus features seems to rely upon low-level
      functional components of the visual pathways. By using a repetition priming
      paradigm, we previously showed that visual area V5/MT is important for holding
      motion direction information, but not spatial position information. Here we
      extend our previous findings and investigate the possible locus of spatial
      position priming. We compare the effect of repetitive transcranial magnetic
      stimulation (rTMS) over right angular gyrus and left and right frontal eye fields
      on priming for spatial position and motion direction. TMS over left frontal eye
      field selectively and significantly reduced priming for spatial position but
      there was no significant effect of TMS over right parietal or right frontal eye
      field. These results suggest that FEF neurons are implicated in short-term memory
      storage of spatial position, and extend and support the idea that memory for
      basic stimulus features is retained within the sensory areas that respond to
      primary stimulus attributes. They add to a growing body of evidence that the
      frontal eye fields are involved in many visual functions independent of eye
      movements.

PMID- 17449068
TI  - Dissociation of the neural correlates of recognition memory according to
      familiarity, recollection, and amount of recollected information.
AB  - The present experiment used fMRI to investigate whether neural correlates of
      recognition memory behave in a manner consistent with the proposal that
      recognition decisions are based on a unidimensional memory strength variable. A
      modified Remember/Know recognition test was used in which participants could
      indicate two levels of recollection. Participants were required to indicate
      whether a test item was new, familiar (known), elicited recollection of general
      contextual details from the study episode (R1 response), or elicited a specific
      recollection of the item with which it was paired at study (R2 response). Little
      evidence could be found to support the view that Remember/Know/New judgments
      reflect variations along a single strength dimension. Instead, the findings
      replicated prior research in indicating that the neural correlates of
      recollection and familiarity can be doubly dissociated. Two recollection
      sensitive regions - left lateral inferior parietal and left fusiform cortex -
      were found to be sensitive to amount of information recollected, as
      operationalized in the contrast between R2 and R1 responses. It is proposed that
      these regions may support the representation of recollected information.

PMID- 17449070
TI  - Effect of the detraining status on high-fat diet induced fat accumulation in the
      adipose tissue and liver in female rats.
AB  - The purpose of the present study was to investigate the effects of a high-fat
      diet (HFD) in previously trained rats that have been detrained for different
      periods. Two groups of female rats were, first, either treadmill trained for 8
      weeks or remained sedentary (Sed). Trained animals, thereafter, remained inactive
      for 4 weeks (Inact-4 weeks), while fed a standard diet, before being submitted to
      a high-fat diet (42% kcal of fat) for an additional 2 or 6 weeks. The order was
      reversed in a 3rd group in which rats were first kept sedentary for 4 weeks
      before being submitted to the same 8-week training program that ended with the
      initiation of the HFD (Inact-0 week). Fat accumulation in the mesenteric depot
      (P<0.05) and in the sum of 3 intra-abdominal (urogenital, retroperitoneal, and
      mesenteric; P=0.065) tissues in response to the HF feeding was higher in trained
      rats kept inactive for 4 weeks than in Sed and Inact-0 week animals. Liver
      triacylglycerol accumulation also showed a tendency to be higher (P<0.07) in
      Inact-4 weeks than in Inact-0 week rats. These changes were not associated with
      significant changes in fat cell diameter and number in the mesenteric adipose
      tissue. When rats in all groups were subdivided into obesity prone (OP) and
      obesity resistant (OR) on the basis of the change in body weight gain in response
      to the HFD, liver lipid infiltration was higher (P<0.01) in OP Inact-4 weeks rats
      than in all other groups. The present results indicate that previously trained
      rats that have been inactive for a while maintain higher body adiposity in
      response to a HFD than in freshly inactive and sedentary rats.

PMID- 17449071
TI  - Exogenous melatonin administration affects self-grooming and conspecific odor
      preferences in long-photoperiod meadow voles (Microtus pennsylvanicus).
AB  - For meadow voles, Microtus pennsylvanicus, seasonal differences exist in self
      grooming and in odor preferences for conspecifics, two behaviors which facilitate
      sexual interactions in this species. Both behaviors are mediated by
      photoperiodically-induced changes in circulating gonadal steroid hormone titers
      which, in turn, can be transduced by the duration of the melatonin signal that a
      seasonally breeding animal receives. The goal of this study was to determine
      whether exogenous melatonin administration affects circulating gonadal steroid
      hormone titers in meadow voles, and whether it influences their odor preferences
      and self-grooming behavior to same- and opposite-sex conspecifics. Long
      photoperiod voles that did not receive exogenous melatonin had higher
      testosterone (males) and estradiol (females) titers than did short-photoperiod
      voles and long-photoperiod voles treated with melatonin for 12 weeks; the latter
      had similar estradiol and testosterone titers. Long-photoperiod voles that did
      not receive melatonin preferred the scent marks of long-photoperiod opposite-sex
      conspecifics and spent more time self-grooming in response to their odors than
      those of either long-photoperiod same-sex, short-photoperiod same-sex, or short
      photoperiod opposite-sex conspecifics. Long-photoperiod voles that received
      melatonin, however, no longer preferred the marks of long-photoperiod opposite
      sex conspecifics and no longer spent more time self-grooming in response to their
      odors, not unlike the odor preferences and self-grooming behavior of short
      photoperiod voles. As a whole, the data suggest that the duration of the
      melatonin signal is likely involved in mediating the photoperiodically-induced
      changes in gonadal steroid hormones that mediate a meadow vole's odor preferences
      for opposite-sex conspecifics and its self-grooming response to those marks.

PMID- 17449072
TI  - Age-related learning and memory impairments in adult-onset hypothyroidism in
      Kunming mice.
AB  - The memory impairment induced by adult-onset hypothyroidism is a common symptom.
      However, the exact onset time that will influence on memory function is still an
      issue of debate. The purpose of this study is to determine the onset effect of
      hypothyroidism on the memory during adulthood. Three age groups of Kunming (KM)
      mice were used, including 2, 8, and 15-month-old mice. Adult-onset hypothyroidism
      was made by adding PTU to drinking water and hypothyroid states were documented
      by the measurement of serum thyroid hormones level. A battery of tasks, i.e.
      novel-object recognition, olfactory discrimination, Morris water maze, was used
      to test mice's memory. The results showed that adult-onset hypothyroidism induced
      the impairment of odor and spatial memory consolidation whereas it did not affect
      visual memory encoding or consolidated spatial memory retention. Age at onset of
      hypothyroidism was an important factor for the memory impairment induced by
      hypothyroidism. The 2-month-old hypothyroid mice had significantly impaired
      abilities in both the olfactory discrimination and the spatial cognitive tasks
      relative to the 2-month-old controls. The 8-month-old hypothyroid mice had only
      impaired ability in the spatial cognitive task relative to the same age controls.
      The 15-month-old hypothyroid mice retained these cognitive abilities relative to
      the same age controls. These results suggested that adult-onset hypothyroidism
      could induce an age- and task-dependent impairment of memory in female KM mice.

PMID- 17449073
TI  - Aryltetralin-lignan formation in two different cell suspension cultures of Linum
      album: deoxypodophyllotoxin 6-hydroxylase, a key enzyme for the formation of 6
      methoxypodophyllotoxin.
AB  - Suspension cultures initiated from two different Linum album seedlings accumulate
      either podophyllotoxin (PTOX, 2.6 mg/g DW) or 6-methoxypodophyllotoxin (6MPTOX,
      5.4 mg/g DW) as main lignans. Two molecules of coniferyl alcohol are dimerized to
      pinoresinol which is converted via several steps into deoxypodophyllotoxin (DOP)
      which seems to be the branching point to PTOX or 6MPTOX biosynthesis. DOP is
      hydroxylated at position 7 to give PTOX by deoxypodophyllotoxin 7-hydroxylase
      (DOP7H). In contrast, 6MPTOX biosynthesis is achieved by DOP hydroxylation at
      position 6 to beta-peltatin by the cytochrome P450 enzyme deoxypodophyllotoxin 6
      hydroxylase (DOP6H). The following methylation to beta-peltatin-A-methylether is
      catalyzed by beta-peltatin 6-O-methyltransferase (betaP6OMT) from which 6MPTOX is
      formed by hydroxylation at position 7 by beta-peltatin-A-methylether 7
      hydroxylase (PAM7H). DOP6H and betaP6OMT could be characterized in protein
      extracts from cell cultures of L. flavum and L. nodiflorum, respectively, and
      here in L. album for the first time. DOP7H and PAM7H activities could not yet be
      detected with protein extracts. Experiments of feeding DOP together with
      inhibitors of cytochrome P450 depending as well as dioxygenase enzymes were
      performed in order to shed light on the type of DOP7H and PAM7H. Growth
      parameters and specific activities of enzymes from the phenylpropane as well as
      the lignan specific biosynthetic pathway were measured during a culture period of
      16 days. From the enzymes studied only the DOP6H showed a differential activity
      sustaining the hypothesis that this enzyme is responsible for the differential
      lignan accumulation in both cell lines.

PMID- 17449074
TI  - Ericifolin: an eugenol 5-O-galloylglucoside and other phenolics from Melaleuca
      ericifolia.
AB  - Ericifolin, an eugenol 5-O-beta-(6'-O-galloylglucopyranoside) possessing the
      naturally unknown phenolic moiety, 5-hydroxyeugenol, together with the two new
      phenolics, 2-O-p-hydroxybenzoyl-6-O-galloyl-(alpha/beta)-4C1-glucopyranose and 3
      methoxyellagic acid 4-O-rhamnopyranoside have been isolated from the
      antibacterial leaves extract of Melaleuca ericifolia. In addition, 19 known
      phenolics were also separated and characterized. All structures were elucidated
      on the basis of analysis of 1H, 13C NMR, HMQC, HMBC and FTMS spectral data.

PMID- 17449075
TI  - Steroidal saponins from Asparagus acutifolius.
AB  - Six new steroidal saponins (1-6) were isolated from the roots of A. acutifolius
      L., together with a known spirostanol glycoside (7). Their structures were
      elucidated mainly by extensive spectroscopic analysis (1D and 2D NMR, FABMS and
      HRESIMS). Compounds 4-7 demonstrated antifungal activity against the human
      pathogenic yeasts C. albicans, C. glabrata and C. tropicalis with MICs values
      between 12.5 and 100 microg/ml.

PMID- 17449076
TI  - Acylated pregnane glycosides from Caralluma russeliana.
AB  - The chloroform extract of the aerial parts of Caralluma russeliana yielded four
      acylated pregnane glycosides, namely russeliosides E-H, three were found now. The
      structures of the compounds were elucidated using MS, 1H NMR, 13C NMR, 1H-1H
      COSY, HMQC, NOESY and HMBC experiments.

PMID- 17449077
TI  - Glycosylation of capsaicin and 8-nordihydrocapsaicin by cultured cells of
      Catharanthus roseus.
AB  - The glycosylation of capsaicin and 8-nordihydrocapsaicin was investigated using
      cultured cells of Catharanthus roseus. In addition to capsaicin 4-O-beta-d
      glucopyranoside (170 microg/g fr. wt of cells), the biotransformation products,
      capsaicin 4-O-(6-O-beta-D-xylopyranosyl)-beta-D-glucopyranoside (116 microg/g fr.
      wt of cells) and capsaicin 4-O-(6-O-alpha-L-arabinopyranosyl)-beta-D
      glucopyranoside (83 microg/g fr. wt of cells), were isolated from the cell
      suspension after three days of incubation with capsaicin. Two other compounds, 8
      nordihydrocapsaicin 4-O-(6-O-beta-D-xylopyranosyl)-beta-D-glucopyranoside (171
      microg/g fr. wt of cells) and 8-nordihydrocapsaicin 4-O-(6-O-alpha-L
      arabinopyranosyl)-beta-D-glucopyranoside (122 microg/g fr. wt of cells), together
      with the known 8-nordihydrocapsaicin 4-O-beta-D-glucopyranoside (204 microg/g fr.
      wt of cells) were also isolated from the cell suspension after incubation with 8
      nordihydrocapsaicin.

PMID- 17449078
TI  - Pyrrolo- and pyridoazepine alkaloids as chemical markers in Stemona species.
AB  - Broad-based phytochemical investigations on 31 Stemona species and geographical
      provenances led to an overview concerning characteristic accumulation trends and
      the distribution of different Stemona alkaloids. Two major metabolic differences
      suggested a taxonomic segregation of the complex Stemona tuberosa group from the
      other species, and was supported by morphological characters. Whereas most of the
      Stemona species were characterised by protostemonine type alkaloids, the S.
      tuberosa group clearly deviated by accumulation trends towards tuberostemonine or
      croomine derived alkaloids belonging to two different skeletal types. Also of
      chemotaxonomic relevance was the structural divergence of protostemonine type
      alkaloids into pyrrolo- or pyridoazepine derivatives represented by stemofoline
      or oxystemokerrine, respectively, as major constituents. Their common occurrence
      in different provenances of S. curtisii, also deviating from the other species by
      various chromosome numbers, deserves special taxonomic attention. Species
      specific chemical markers were given by the unique accumulation of
      didehydrostemofoline (=asparagamine A) in S. collinsae and stemokerrine in S.
      kerrii. In contrast to previous reports, no bisdehydro derivatives with an
      aromatic pyrrole ring were detected supporting the hypothesis that these
      alkaloids are artifacts. A new stereoisomer of tuberostemonine was isolated and
      identified by spectroscopic methods.

PMID- 17449079
TI  - In vivo particle polymorphism results from deletion of a N-terminal peptide
      molecular switch in brome mosaic virus capsid protein.
AB  - The interaction between brome mosaic virus (BMV) coat protein (CP) and viral RNA
      is a carefully orchestrated process resulting in the formation of homogeneous
      population of infectious virions with T=3 symmetry. Expression in vivo of either
      wild type or mutant BMV CP through homologous replication never results in the
      assembly of aberrant particles. In this study, we report that deletion of amino
      acid residues 41-47 from the N-proximal region of BMV CP resulted in the assembly
      of polymorphic virions in vivo. Purified virions from symptomatic leaves remain
      non-infectious and Northern blot analysis of virion RNA displayed packaging
      defects. Biochemical characterization of variant CP by circular dichroism and
      MALDI-TOF, respectively, revealed that the engineered deletion affected the
      protein structure and capsid dynamics. Most significantly, CP subunits
      dissociated from polymorphic virions are incompetent for in vitro reassembly.
      Based on these observations, we propose a chaperon-mediated mechanism for the
      assembly of variant CP in vivo and also hypothesize that (41)KAIKAIA(47) N
      proximal peptide functions as a molecular switch in regulating T=3 virion
      symmetry.

PMID- 17449080
TI  - Characterization of a baculovirus lacking the DBP (DNA-binding protein) gene.
AB  - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) encodes two
      proteins that possess properties typical of single-stranded DNA-binding proteins
      (SSBs), late expression factor-3 (LEF-3), and a protein referred to as DNA
      binding protein (DBP). Whereas LEF-3 is a multi-functional protein essential for
      viral DNA replication, transporting helicase into the nucleus, and forms a stable
      complex with the baculovirus alkaline nuclease, the role for DBP in baculovirus
      replication remains unclear. Therefore, to better understand the functional role
      of DBP in viral replication, a DBP knockout virus was generated from an AcMNPV
      bacmid and analyzed. The results of a growth curve analysis indicated that the
      dbp knockout construct was unable to produce budded virus indicating that dbp is
      essential. The lack of DBP does not cause a general shutdown of the expression of
      viral genes, as was revealed by accumulation of early (LEF-3), late (VP39), and
      very late (P10) proteins in cells transfected with the dbp knockout construct. To
      investigate the role of DBP in DNA replication, a real-time PCR-based assay was
      employed and showed that, although viral DNA synthesis occurred in cells
      transfected with the dbp knockout, the levels were less than that of the control
      virus suggesting that DBP is required for normal levels of DNA synthesis or for
      stability of nascent viral DNA. In addition, analysis of the viral DNA replicated
      by the dbp knockout by using field inversion gel electrophoresis failed to detect
      the presence of genome-length DNA. Furthermore, analysis of DBP from infected
      cells indicated that similar to LEF-3, DBP was tightly bound to viral chromatin.
      Assessment of the cellular localization of DBP relative to replicated viral DNA
      by immunoelectron microscopy indicated that, at 24 h post-infection, DBP co
      localized with nascent DNA at distinct electron-dense regions within the nucleus.
      Finally, immunoelectron microscopic analysis of cells transfected with the dbp
      knockout revealed that DBP is required for the production of normal-appearing
      nucleocapsids and for the generation of the virogenic stroma.

PMID- 17449081
TI  - Cortical specialization for concentric shape processing.
AB  - It is current dogma that neurons in primary visual cortex extract local edges
      from the scene, from which later visual areas reconstruct more meaningful shapes.
      In intermediate areas, such as area V4, responses are driven by features more
      complex than local oriented edges but more basic than meaningful shapes. The
      present study was motivated by the proposal that concentric (circular) shape
      processing is an important aspect of intermediate shape processing and is
      proposed to occur in area V4. However, previous studies are not able to
      discriminate between the number of orientations within the image nor how these
      orientations vary across space (orientation gradient, contrast or curvature) as
      opposed to concentric shape processing per se. We address the question whether V4
      responses are driven by curvature or circularity. We use fMRI and tightly
      controlled narrowband stimuli with identical local and global properties. These
      patterns either form random or circular patterns with tightly matched orientation
      gradients and therefore similar curvature. We find stronger responses to circular
      patterns in areas V3/VP and V4. Our results suggest that extracting circular
      shape is an important step in intermediate shape processing.

PMID- 17449082
TI  - Cortical processing of visual motion in young infants.
AB  - High-density EEG was used to investigate the cortical processing of a rotating
      visual pattern in 2-, 3-, and 5-month-old infants and in adults. Motion induced
      ERP in the parietal and the temporal-occipital border regions (OT) was elicited
      at all ages. The ERP was discernable in the 2-months-olds, significant and
      unilateral in the 3-month-olds and significantly bilateral in the 5-month-olds
      and adults. The motion induced ERP in the primary visual area was absent in the 2
      month-olds and later than in the OT area for the 3-month-olds indicating that
      information to OT may be supplied by the V1 bypass at these ages. The results are
      in agreement with behavioural and psychophysical data in infants.

PMID- 17449083
TI  - Removal of native coliphages and coliform bacteria from municipal wastewater by
      various wastewater treatment processes: implications to water reuse.
AB  - The efficacy of a conventional activated sludge wastewater treatment process and
      the membrane bioreactor technology in removing microbial pathogens was
      investigated. Total and fecal coliforms and somatic and F-specific coliphages
      were used as indicators of pathogenic bacteria and viruses. Up to 5.7 logs
      removal of coliforms and 5.5 logs of coliphages were observed in the conventional
      treatment process with advanced tertiary treatment. Addition of chemical
      coagulants seemed to improve the efficacy of primary and secondary treatment for
      microorganism removal. Complete removal of fecal coliforms and up to 5.8 logs
      removal of coliphages was observed in the MBR system. It was shown that the MBR
      system was capable of high removal of coliphages despite the variation in feed
      coliphage concentrations. The results of this study indicated that the MBR system
      can achieve better microbial removal in far fewer steps than the conventional
      activated sludge process with advanced tertiary treatment. The final effluent
      from either treatment processes can be potentially reused.

PMID- 17449084
TI  - Estimating biozone hydraulic conductivity in wastewater soil-infiltration systems
      using inverse numerical modeling.
AB  - During operation of an onsite wastewater treatment system, a low-permeability
      biozone develops at the infiltrative surface (IS) during application of
      wastewater to soil. Inverse numerical-model simulations were used to estimate the
      biozone saturated hydraulic conductivity (K(biozone)) under variably saturated
      conditions for 29 wastewater infiltration test cells installed in a sandy loam
      field soil. Test cells employed two loading rates (4 and 8cm/day) and 3 IS
      designs: open chamber, gravel, and synthetic bundles. The ratio of K(biozone) to
      the saturated hydraulic conductivity of the natural soil (K(s)) was used to
      quantify the reductions in the IS hydraulic conductivity. A smaller value of
      K(biozone)/K(s,) reflects a greater reduction in hydraulic conductivity. The IS
      hydraulic conductivity was reduced by 1-3 orders of magnitude. The reduction in
      IS hydraulic conductivity was primarily influenced by wastewater loading rate and
      IS type and not by the K(s) of the native soil. The higher loading rate yielded
      greater reductions in IS hydraulic conductivity than the lower loading rate for
      bundle and gravel cells, but the difference was not statistically significant for
      chamber cells. Bundle and gravel cells exhibited a greater reduction in IS
      hydraulic conductivity than chamber cells at the higher loading rates, while the
      difference between gravel and bundle systems was not statistically significant.
      At the lower rate, bundle cells exhibited generally lower K(biozone)/K(s) values,
      but not at a statistically significant level, while gravel and chamber cells were
      statistically similar. Gravel cells exhibited the greatest variability in
      measured values, which may complicate design efforts based on K(biozone)
      evaluations for these systems. These results suggest that chamber systems may
      provide for a more robust design, particularly for high or variable wastewater
      infiltration rates.

PMID- 17449085
TI  - Grinding and sieving soil affects the availability of organic contaminants: a
      kinetic analysis.
AB  - Field contaminated soils are often homogenized before application in bioassays
      and chemical assays that estimate the (bio)availability of their contaminants.
      The homogenization of the soil might affect the availability, and thereby the
      outcome of a bioassay might not reflect field situations. In this study, uptake
      kinetics of polycyclic aromatic hydrocarbons (PAH) by a negligible depletive
      passive sampler exposed to a ground and non-ground field contaminated soil were
      tested. The measurements illustrate how freely dissolved pore water
      concentrations of contaminants can be affected by soil treatment. It took more
      than a month, and over a year to reach steady state in the passive sampler
      exposed to the ground and non-ground soil, respectively. The uptake rate seemed
      to be limited by desorption from the soil, even though the fiber only extracted
      0.2% of the soil-sorbed PAH at maximum. If these observations are translated to
      the field situation, where contaminants are not homogeneously distributed and
      disappear by (bio)degradation or physical transport processes, it is unlikely
      that pore water concentrations are solely determined by a thermodynamic
      equilibrium. Hence, exposure of organisms in these soils cannot always be
      estimated by sorption studies and an equilibrium partitioning approach.

PMID- 17449086
TI  - Co-cropping for phyto-separation of zinc and potassium from sewage sludge.
AB  - The use of sewage sludge as a fertilizer and soil amendment has resulted in high
      concentrations of heavy metals in the soil limiting its use. The present study
      was carried out to find the possibility of phyto-separating toxic and beneficial
      elements from the sludge using suitable plants. Of the five plants tested the
      hyperaccumulator Sedum alfredii H achieved the greatest removal of Zn, while
      shoots of Alocasia marorrhiza accumulated high content of K. Co-cropping these
      two plants on the sludge verified the previous observations on A. marorrhiza and
      the shoots of this plant could accumulate more than 120 g K kg(-1) dry matter in
      the median growth stage. Zn hyperaccumulated in Sedum's shoots to an extent more
      than 10 g kg(-1) dry matter; K concentrated five to ten times in the Alocasia's
      shoots which could be used as a good organic-K-fertilizer. Hence, the two
      elements were simultaneously phytoseparated and could be recycled. Furthermore,
      cultivation of plants in the sludge resulted in significant decreases in total Zn
      but kept the favorable agronomic characteristics of the sludge material, such as
      pH, organic matter content, and NPK concentrations and ameliorated its biological
      stability. These results suggest that simultaneous phyto-separation of toxic and
      beneficial elements from sewage sludge are possible by co-cropping using specific
      plants without the input of any chemicals.

PMID- 17449087
TI  - Heterogeneous photocatalytic degradation of prometryn in aqueous solutions under
      UV-Vis irradiation.
AB  - In this study, the heterogeneous photocatalytic degradation of prometryn using
      TiO(2) as photocatalyst was investigated. The main objectives of the study were:
      (I) to evaluate the kinetics of the pesticide disappearance, (II) to compare the
      photocatalytic efficiency of two different types of TiO(2), (III) to examine the
      influence of various parameters such as initial concentration of pesticide or
      catalyst and presence of oxidants (H(2)O(2) and K(2)S(2)O(8)), (IV) to evaluate
      the degree of mineralization and (V) to assess the detoxification efficiency of
      the studied processes. The experiments were carried out in a 500 ml pyrex UV
      reactor equipped with a 125 W high-pressure mercury lamp surrounded by a pyrex
      filter blocking wavelengths below 290 nm. Prometryn concentration was determined
      using HPLC. It was found that the degradation of the pesticide follows the first
      order kinetics according to the Langmuir-Hinshelwood model. Parameters like the
      type and concentration of the catalyst affect the degradation rate. A synergistic
      effect was observed when an oxidant was added in the TiO(2) suspensions
      increasing the reaction rate of photodegradation. In order to examine the extent
      of pesticide mineralization, DOC measurements were carried out. After 6h of
      illumination, mineralization was achieved up to almost 70%. The toxicity of the
      treated solution was evaluated using the Microtox test based on the luminescent
      bacteria Vibrio fisheri, in order to compare the acute toxicity of prometryn and
      its photoproducts. The detoxification efficiency was found to be dependent on the
      studied system and it did not follow the rate of pesticide disappearance.

PMID- 17449088
TI  - Venous thromboembolism after orthopedic surgery: implications of the choice for
      prophylaxis.
AB  - INTRODUCTION: Venous thromboembolism (VTE) is an important cause of morbidity and
      mortality following major orthopedic surgeries. In clinical trials, fondaparinux
      and low molecular weight heparins have been shown to be more effective than
      unfractionated heparin (UFH) in preventing VTE. We retrospectively analyzed a
      large hospital discharge database to assess the occurrence of clinically detected
      VTE as a function of the injectable antithrombotic agent used for VTE prophylaxis
      in orthopedic surgery. METHODS: The Premier's Perspective database, representing
      over 500 hospitals across the US, was utilized to identify patients receiving
      dalteparin, enoxaparin, fondaparinux, or UFH following hip or knee replacement or
      hip fracture surgery between January 2003 and March 2005. The primary outcome was
      the proportion of patients in each cohort with a VTE, while secondary outcomes
      included VTE occurrence during index hospitalization, and proportion of patients
      with a VTE-associated hospital readmission. RESULTS: A total of 144,806 patients
      were included in the study. Significantly fewer fondaparinux patients experienced
      a VTE event (1.5%) compared to enoxaparin (2.3%), dalteparin (2.1%), and UFH
      (4.2%). After controlling for baseline covariates, the odds of experiencing a VTE
      was significantly higher for other treatments when compared to fondaparinux (odds
      ratios: dalteparin=1.22 [95% CI: 1.01 to 1.46] p=0.0370; enoxaparin=1.39 [1.19 to
      1.62], p<0.0001; UFH=1.98 [1.67 to 2.34], p<0.0001). Significantly fewer
      fondaparinux-treated patients experienced an event during the index
      hospitalization or were readmitted for a VTE compared to other treatments.
      CONCLUSIONS: Similar to clinical trial findings, patients receiving fondaparinux
      in this study experienced fewer VTE events following orthopedic surgeries.

PMID- 17449089
TI  - Venous thromboembolism prevention in gynecologic cancer surgery: a systematic
      review.
AB  - OBJECTIVES: Advanced age, pelvic surgery, and the presence of malignancy place
      gynecologic oncology patients at high risk for venous thromboembolism (VTE). This
      study was designed to systematically analyze the world's literature on VTE in
      these patients and determine the optimal prophylaxis regimen. METHODS:
      Computerized searches of Pubmed, Ovid, DARE, ACP Journal Club, Cochrane Database
      of Systematic Reviews, and Cochrane Controlled Trials Registry 1966-2005 were
      performed, as well as EMBASE 1980-2005. Major conferences and target references
      were hand-searched. Inclusion criteria were randomized controlled trials (RCTs)
      evaluating VTE prophylaxis with heparin, low-molecular-weight heparin (LMWH), and
      sequential compression devices (SCD). The search yielded 278 articles; 11 met
      inclusion criteria. Data were abstracted by one author and analyzed with the
      Mantel-Haenszel method. RESULTS: The analysis of heparin-versus-control revealed
      a significant decrease in DVT in patients receiving heparin (RR=0.58, 95% CI 0.35
      0.95). There were no significant differences in EBL or transfusions between the
      two groups. In the 320 patients in the heparin vs. LMWH studies, there was no
      significant difference in DVT (RR 0.91, 95% CI 0.38-2.17), although power
      analysis demonstrated insufficient numbers to show a difference. No patient in
      either group required re-exploration for bleeding. CONCLUSIONS: All gynecologic
      cancer patients should receive VTE prophylaxis. Although heparin, LMWH, and SCD
      have been shown to be safe and effective, due to the paucity of data in the
      gynecologic oncology literature, no one prevention modality can be considered
      superior at this time. Adequately powered RCTs are urgently needed to determine
      the optimal regimen in these high-risk patients.

PMID- 17449090
TI  - Evaluation of acute bis(7)-tacrine treatment on behavioral functions in 17-day
      old and 30-day-old mice, with attention to drug toxicity.
AB  - Bis(7)-tacrine was evaluated for efficacy on memory retention in mice 17 days of
      age and 30 days of age. The tests used were a passive-avoidance response test and
      a measure of spontaneous motor activity. Also, possible drug-induced
      hepatotoxicity and acute drug toxicity were evaluated. Behavioral studies were
      performed using a step-through task and an open-field test with a 24-h interval
      between training and evaluation tests. Bis(7)-tacrine (0.06-20 micromol/kg) was
      subcutaneously injected 30 min prior to the first session of both test types.
      During the training session of the step-through task, bis(7)-tacrine treatment
      reduced (by 46%, P<0.01) the number of avoidable electric shocks (footshocks)
      only at a high dose of 20 micromol/kg in mice 17 days of age, but dose
      dependently decreased the number of footshocks (10-56%, P<0.001) in mice 30 days
      of age. Bis(7)-tacrine treatment at all doses tested did not produce any
      detectable changes in retention latency in mice 17 days of age, but the drug
      significantly prolonged retention latency at low doses (1.25 and 2.50
      micromol/kg), and not high doses (5-20 micromol/kg), in mice 30 days of age. In
      the open-field test, bis(7)-tacrine decreased spontaneous motor activity in the
      acquisition session only at a high dose of 20 micromol/kg in mice 17 days of age
      and 30 days of age (by 28 and 45%, respectively), but did not affect spontaneous
      motor activity in the recall session. Bis(7)-tacrine treatment at a dose of 20
      micromol/kg produced a more potent hepatotoxic effect in mice 30 days of age than
      in mice 17 days of age, (P<0.05), and the drug caused acute toxicity with
      comparable potencies in mice of both age groups. In conclusion, mice 30 days of
      age seemed to be more sensitive than mice 17 days of age to bis(7)-tacrine
      induced cognitive function enhancement and hepatotoxicity. Bis(7)-tacrine appears
      to be more potent and more selective as a cognitive function-enhancing agent than
      tacrine.

PMID- 17449091
TI  - Protein-flexible chain polymer interactions to explain protein partition in
      aqueous two-phase systems and the protein-polyelectrolyte complex formation.
AB  - Complexes formation between two model proteins (catalase and chymotrypsin) and
      polyelectrolytes (polyvinyl sulphonate and polyacrilic acid) and a non-charged
      flexible chain polymer (PCF) as polyethylene propylene oxide (molecular mass
      8400) was studied by a spectroscopy technique combination: UV absorption,
      fluorescence emission and circular dichroism. All the polymers increase the
      protein surface hydrophobicity (S(0)) parameter value as a proof of the
      modification of the protein surface exposed to the solvent. Chymotrypsin showed
      an increase in its biological activity in polymer presence, which suggests a
      change in the superficial microenvironment. The decrease in the biological
      activity of catalase might be due to a competition between the polymer and the
      substrate. This result agrees with the polymer effect on the catalase superficial
      hydrophobic area. It was found that, when flexible chain polymers increase
      protein stability and the enzymatic activity they could be used to isolate this
      enzyme without inducing loss of protein enzymatic activity. Our findings suggest
      that the interactions are dependent on the protein physico-chemical parameters
      such as: isoelectric pH, hydrophobic surface area, etc.

PMID- 17449093
TI  - Development of an antigen-presenting cell-targeted DNA vaccine against melanoma
      by mannosylated liposomes.
AB  - As part of our research involving the targeted delivery of plasmid DNA (pDNA) to
      antigen-presenting cells (APCs), we developed mannosylated cationic liposomes: N
      [1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/cholesten-5
      yloxy-N-(4-((1-imino-2-D-thiomannosyl-ethyl)amino)butyl)formamide (Man-C4
      Chol)/Chol (Man liposomes). In this study, we used melanoma-associated antigen
      expressing pDNA; pUb-M and Man liposomes to create a novel APC-targeted DNA
      vaccine against melanoma and examined its potency by measuring the Ub-M mRNA
      expression in splenic dendritic cells and macrophages, the cytotoxic T lymphocyte
      (CTL) activity against melanoma B16BL6 cells and the melanoma B16BL6-specific
      anti-tumor effect after intraperitoneal (i.p.) administration. We verified that
      Man lipoplex induces significantly higher pUb-M gene transfection into dendritic
      cells and macrophages than unmodified lipoplex and naked DNA and it also strongly
      induces CTL activity against melanoma, inhibits its growth and prolongs the
      survival after tumor challenge compared with unmodified liposomes and the
      standard method (naked pDNA, intramuscular (i.m.)). These results demonstrate
      that Man liposomes are a potent APCs-targeted vector that induce strong
      immunopotency of DNA vaccine against melanoma.

PMID- 17449092
TI  - Influence of engineered titania nanotubular surfaces on bone cells.
AB  - A goal of current orthopedic biomaterials research is to design implants that
      induce controlled, guided, and rapid healing. In addition to acceleration of
      normal wound healing phenomena, these implants should result in the formation of
      a characteristic interfacial layer with adequate biomechanical properties. To
      achieve these goals, however, a better understanding of events at the bone
      material interface is needed, as well as the development of new materials and
      approaches that promote osseointegration. Using anodization, titania interfaces
      can be fabricated with controlled nanoarchitecture. This study demonstrates the
      ability of these surfaces to promote osteoblast differentiation and matrix
      production, and enhance short- and long-term osseointegration in vitro. Titania
      nanotubular surfaces were fabricated using an anodization technique. Marrow
      stromal cells (MSCs) were isolated from male Lewis rats and seeded on these
      surfaces along with control surfaces. The interaction of cells with these
      surfaces was investigated in terms of their ability to adhere, proliferate and
      differentiate on them. The experiments were repeated three times with cells from
      different cultures. All the results were analyzed using analysis of variance
      (ANOVA). Statistical significance was considered at p<0.05. Furthermore, in vivo
      biocompatibility was assessed by implanting surfaces subcutaneously in male Lewis
      rat and performing histological analysis after 4 weeks. Our results indicate that
      the nanotubular titania surfaces provide a favorable template for the growth and
      maintenance of bone cells. The cells cultured on nanotubular surfaces showed
      higher adhesion, proliferation, ALP activity and bone matrix deposition compared
      to those grown on flat titanium surfaces. In vivo biocompatibility results
      suggest that nanotubular titania does not cause chronic inflammation or fibrosis.
      The fabrication routes of titania nano-architectures are flexible and cost
      effective, enabling realization of desired platform topologies on existing non
      planar orthopedic implants.

PMID- 17449094
TI  - Hodgkin lymphoma in a mutated ZAP-70 negative B-cell Chronic Lymphocytic Leukemia
      patient.

PMID- 17449095
TI  - Expression analysis of the acute phase response in channel catfish (Ictalurus
      punctatus) after infection with a Gram-negative bacterium.
AB  - The acute phase response (APR) is a set of metabolic and physiological reactions
      occurring in the host in response to tissue infection or injury and is a crucial
      component of the larger innate immune response. The APR is best characterized by
      dramatic changes in the concentration of a group of plasma proteins known as
      acute phase proteins (APPs) which are synthesized in the liver and function in a
      wide range of immunity-related activities. Utilizing a new high-density in situ
      oligonucleotide microarray, we have evaluated the APR in channel catfish liver
      following infection with Edwardsiella ictaluri, a bacterial pathogen that causes
      enteric septicemia of catfish. Our catfish microarray design (28K) builds upon a
      previous 19K channel catfish array by adding recently sequenced immune
      transcripts from channel catfish along with 7159 unique sequences from closely
      related blue catfish. The analysis of microarray results using a traditional 2
      fold change in gene expression cutoff and a 10% false-discovery rate revealed a
      well-developed APR in catfish, with particularly high upregulation (>50-fold) of
      genes involved in iron homeostasis (i.e. intelectin, hemopexin, haptoglobin,
      ferritin, and transferrin). Other classical APP genes upregulated greater than 2
      fold included coagulation factors, proteinase inhibitors, transport proteins, and
      complement components. Upregulation of the majority of the complement cascade was
      observed including the membrane attack complex components and complement
      inhibitors. A number of pathogen recognition receptors (PRRs) and chemokines were
      also differentially expressed in the liver following infection. Independent
      testing of a selection of differentially expressed genes with real-time RT-PCR
      confirmed microarray results.

PMID- 17449096
TI  - Comparison of fathead minnow ovary explant and H295R cell-based steroidogenesis
      assays for identifying endocrine-active chemicals.
AB  - An in vitro steroidogenesis assay using H295R human adenocarcinoma cells has been
      suggested as a possible alternative to gonad explant assays for use as a Tier I
      screening assay to detect endocrine active chemicals capable of modulating
      steroid hormone synthesis. This study is one of the first to investigate the
      utility of the H295R assay for predicting effects and/or understanding mechanisms
      of action across species and tissues. Six chemicals, including one selective
      aromatase inhibitor (fadrozole), four fungicides (fenarimol, ketoconazole,
      prochloraz, and vinclozolin), and one herbicide (prometon), were tested in both
      the H295R steroidogenesis assay, and an in vitro steroidogenesis assay using
      fathead minnow ovary explants. All six chemicals caused significant alterations
      in 17beta-estradiol (E2) and/or testosterone (T) production in vitro. Effects of
      ketoconazole, prochloraz, and prometon were similar in both assays. However,
      there were differences in the profile of responses for T for fadrozole and
      fenarimol, and for T and E2 for vinclozolin. In terms of sensitivity, steroid
      production in the H295R assay was most sensitive for detecting the effects of
      fadrozole, fenarimol, and prochloraz, but was less sensitive than the fathead
      minnow ovary explant assay to the effects of ketoconazole and vinclozolin. The
      H295R assay was consistently less variable (among replicates) than the fathead
      minnow ovary explant assay. However, the ovary explant assay was more predictive
      of in vivo effects of the six chemicals on fathead minnows than the H295R system.
      Further characterization of autoregulatory capacities, interaction of steroid
      hormone receptor pathways with steroidogenesis, and metabolic capabilities of
      each system are needed for either system to provide clear and informative
      insights regarding a chemical's mechanism of action. Overall, however, results of
      this study suggest that both the H295R and fathead minnow ovary explant assays
      have utility for identifying endocrine-active chemicals in screening-type
      applications.

PMID- 17449097
TI  - Accuracy of eyewitness identification is significantly associated with
      performance on a standardized test of face recognition.
AB  - OBJECTIVES: This study assessed the relationship between Eyewitness Accuracy
      regarding a person met under conditions of high stress and performance on a
      standardized, neutral test of memory for human faces. METHOD: Fifty-three U.S.
      Army personnel were exposed to interrogation stress. Forty-eight hours later,
      participants were administered the Weschler Face Test and then asked to identify
      the one interrogator who they had encountered 48 h earlier. RESULTS: A
      significant positive relationship was observed between performance on the
      Weschler Face Test and performance on the Eyewitness task. Inaccurate
      eyewitnesses exhibited more False Negative errors when performing the Weschler
      Face Test. DISCUSSION: Trait ability to remember human faces may be related to
      how accurately people recall faces that are associated with highly emotional
      circumstances. Detection probability methods, such as ROC curve analyses, may be
      of assistance to forensic examiners, the police, and the courts, when assessing
      the probability that eyewitness evidence is accurate.

PMID- 17449098
TI  - The governance of human genetic research databases in mental health research.
AB  - The field of mental health offers a valuable context in which to examine new
      challenges presented by human genetic research databases to the legal, ethical
      and regulatory frameworks for human genetic research. Longitudinal prospective
      genetic research of psychiatric disorders often involves access to human genetic
      research databases and to stored tissue for future uses that cannot be specified
      at the time the patient consents to their collection. The potential of such
      research to contribute to an improved understanding and treatment of complex
      genetic diseases such as schizophrenia presupposes sound ethical, legal and
      regulatory frameworks to ensure public trust and preparedness to participate in
      such research. This article provides a brief overview of some of the ethical and
      legal challenges posed by human genetic research databases and their implications
      for how genetic research should be conducted in the field of mental health.

PMID- 17449099
TI  - Motives for maternal filicide: results from a study with female forensic
      patients.
AB  - The objective of this study was to examine different motivational factors,
      leading mothers to commit neonaticidal, infanticidal or filicidal acts. This
      study was based on data gathered through a retrospective chart review of all
      filicidal women admitted to the Mid-Hudson Forensic Psychiatric Hospital in New
      York State (MHFPC) between 1976 and 2000 (n=57). Because our sample was drawn
      from MHFPC records it excludes filicidal mothers who went directly to prison. Our
      women were either found not competent to stand trial, or found not guilty by
      reason of insanity, or were convicted offenders who were seriously mentally ill
      and were not sent to prison. Fourteen percent committed neonaticide, meaning that
      they killed their child within the first day of its life; 21% killed the child
      after the first day but before it reached its first birthday (infanticide); and
      65% committed filicide by murdering a child older than one. Two groups of women
      could be identified as having different motivational profiles: The neonaticidal
      mothers were mostly troubled by psychosis and social problems while the filicidal
      women were defined as severely depressed, with a history of self-directed
      violence and a high rate of suicide attempts following the filicidal offense.

PMID- 17449100
TI  - Effects of seven organic pollutants on soil nematode Caenorhabditis elegans.
AB  - Caenorhabditis elegans is a free-living soil nematode that is commonly used as a
      model for toxicity tests. The aim of this study was to investigate the toxicity
      of seven organic pollutants: four azaarenes (quinoline, acridine, phenazine, and
      1,10-phenanthroline), short-chain chlorinated paraffins, and two
      organochlorinated pesticides (toxaphene and hexachlorobenzene). The exposure to
      all chemicals was carried out in three test media (soil, agar, and aquatic
      medium), and adult mortality was evaluated after 24 and 48 h. Toxaphene was the
      most toxic substance with LC(50) (48 h) of 379 mg/kg in the soil and 0.2 mg/L in
      the aquatic medium. Quinoline was the most toxic chemical in agar test with
      LC(50) (48 h) of 10 mg/L. HCB showed a very low toxicity in all tests, maybe due
      to its very low water solubility. Longer than 24-h test duration was found
      necessary for getting more correct data on toxicity. In comparison with other
      studies, C. elegans was less sensitive than other soil invertebrates. Different
      response might be attributed to different exposure routes and shorter test
      duration. Equilibrium partitioning theory was used to calculate K(oc) from
      results of soil and aquatic tests but this approach was found not working. Our
      results suggest that the tests with nematode C. elegans should be included to the
      battery of tests for risk assessment of POPs in soil.

PMID- 17449101
TI  - The nested open reading frame in the Epstein-Barr virus nuclear antigen-1 mRNA
      encodes a protein capable of inhibiting antigen presentation in cis.
AB  - Herpesviruses employ many mechanisms to evade the immune response, allowing them
      to persist life-long in their hosts. The Epstein-Barr virus (EBV) nuclear antigen
      1 (EBNA-1) and, more recently, the latency-associated nuclear antigen 1 (LANA-1)
      of the Kaposi Sarcoma Herpesvirus have been shown to function as in cis-acting
      inhibitors of antigen presentation. In both proteins, long simple repeat elements
      are responsible for the inhibition, but the sequences of these repeats are
      strongly dissimilar. Intriguingly, EBNA-1 mRNA contains a large nested open
      reading frame that codes for a 40.7kDa strongly acidic protein, in addition to
      the full-length EBNA-1. This protein, here called pGZr, has a 230 amino-acids
      long glycine, glutamine, and glutamic acid-rich repeat ('GZ' repeat), highly
      similar (65% amino-acid identity) to the acidic repeat of LANA-1. To evaluate if
      pGZr, like EBNA-1 and LANA-1, can inhibit antigen presentation in cis, we fused
      the nested ORF with the E. coli-derived LacZ gene encoding beta-galactosidase.
      Whereas cells producing the unmodified beta-galactosidase readily present the H
      2L(d)-restricted CTL epitope TPHPARIGL, which resides in the C-terminal region of
      beta-galactosidase, cells producing the pGZr-beta-galactosidase fusion protein do
      not. Also shorter fragments of the repeat can inhibit peptide presentation. Even
      though the physiological function of pGZr remains to be elucidated, the GZ-repeat
      protein may be valuable as inhibitor of presentation of antigenic peptides
      derived from transgenes in gene therapy.

PMID- 17449102
TI  - What can make the difference? Premature birth and maternal sensitivity at 3
      months of age: the role of attachment organization, traumatic reaction and baby's
      medical risk.
AB  - The influence of prematurity and maternal attachment organization on sensitivity
      was investigated in 40 mother-infant dyads. Results show a main effect of
      attachment and an interaction between attachment and prematurity. Sensitivity was
      differently associated with medical risk and mothers' traumatic reaction,
      depending on the quality of attachment.

PMID- 17449103
TI  - Signature tunes in mothers' speech to infants.
AB  - The purpose of the present investigation was to determine whether mothers use
      discernible tunes (i.e., specific interval sequences) in their speech to infants
      and whether such tunes are individually distinctive. Mothers were recorded
      speaking with their infants on two occasions separated by 1 week or more.
      Examination of the tunes of each mother revealed discernible tunes and frequent
      repetitions of tunes within and across sessions. Comparisons of utterances with
      the most common pitch contour (i.e., rising), both within and across mothers,
      revealed interval patterns that were individually distinctive, or unique. The
      findings confirm the prominence of tunes and the presence of signature tunes in
      maternal speech to infants.

PMID- 17449104
TI  - Metabolism and biological functions of two phosphorylated sphingolipids,
      sphingosine 1-phosphate and ceramide 1-phosphate.
AB  - Sphingolipids are major lipid constituents of the eukaryotic plasma membrane.
      Without certain sphingolipids, cells and/or embryos cannot survive, indicating
      that sphingolipids possess important physiological functions that are not
      substituted for by other lipids. One such role may be signaling. Recent studies
      have revealed that some sphingolipid metabolites, such as long-chain bases (LCBs;
      sphingosine (Sph) in mammals), long-chain base 1-phosphates (LCBPs; sphingosine 1
      phosphate (S1P) in mammals), ceramide (Cer), and ceramide 1-phosphate (C1P), act
      as signaling molecules. The addition of phosphate groups to LCB/Sph and Cer
      generates LCBP/S1P and C1P, respectively. These phospholipids exhibit completely
      different functions than those of their precursors. In this review, we describe
      recent advances in understanding the functions of LCBP/S1P and C1P in mammals and
      in the yeast Saccharomyces cerevisiae. Since LCB/Sph, LCBP/S1P, Cer, and C1P are
      mutually convertible, regulation of not only the total amount of the each lipid
      but also of the overall balance in cellular levels is important. Therefore, we
      describe in detail their metabolic pathways, as well as the genes involved in
      each reaction.

PMID- 17449105
TI  - A new stochastic tridimensional model of neonatal rat spinal motoneuron for
      investigating compartmentalization of neuronal conductances and their influence
      on firing.
AB  - During postnatal development spinal motoneurons play a major role in expressing
      basic behaviours like reflex reactions and in allowing the onset of the locomotor
      programme. For this purpose it is useful to clarify how various inputs are
      integrated at the level of the motoneuron soma to generate phasic or rhythmic
      firing. Although existing models of motoneurons have indicated the distributed
      role of certain conductances in regulating firing, it is unclear how the spatial
      distribution of certain currents is ultimately shaping motoneuron output. Thus,
      it would be helpful to build a bridge between histological and
      electrophysiological data. The present report is based on the construction of a
      3D motoneuron model based on available parameters applicable to the neonatal
      spinal cord. The presented algorithm allows building up a complex, variable
      dendrogram which, together with the somatic and axonic compartments, enables
      strategic location of certain voltage or ligand gated conductances and simulation
      of resulting electrical behaviour. One application of the present model has been
      exploring the functional location of the recently reported cystic fibrosis
      transmembrane conductance regulator (CFTR) which controls Cl(-) homeostasis of
      postnatal motoneurons. The 3D model is made available for free, user friendly use
      via the dedicated web site http://www.mn-morphology.org.

PMID- 17449107
TI  - Systematic review of the depressive symptoms associated with vascular conditions.
AB  - BACKGROUND: Numerous studies report a positive association between the presence
      of vascular conditions and depression; however, it is unclear whether this
      presents a distinct subtype of depression. METHOD: A comprehensive literature
      search of Medline was conducted in order to identify studies that have compared
      symptoms of those with depression in the presence and absence of vascular
      factors. AIMS: To provide a systematic review of studies that have attempted to
      characterise the depressive symptomatology associated with vascular factors. To
      establish whether the evidence for a subtype is sufficient to be of use in
      clinical settings. RESULTS: Thirteen publications were identified as relevant to
      the investigation. Study design and definition of vascular factors varied greatly
      between studies. Depression in the presence of vascular conditions was associated
      with poor motivation, lack of energy and psychomotor change in some studies,
      though these findings were inconsistent. Many other possible distinctive features
      were reported in individual publications but were not consistent enough to be
      used confidently as a diagnostic feature. CONCLUSION: At present, there does not
      appear to be sufficient evidence to support a clinically-recognisable subtype of
      vascular depression.

PMID- 17449106
TI  - Dopamine D4 receptor knockout mice exhibit neurochemical changes consistent with
      decreased dopamine release.
AB  - Dopamine D4 receptor (D4R) knockout mice (D4R-/-) provided for unique
      neurochemical studies designed to understand D4R contributions to dopamine (DA)
      regulation. In this study, post-mortem brain tissue content of DA did not differ
      between D4R+/+ and D4R-/- mice in the striatum (Str) or nucleus accumbens core
      (NAc). However, there was a significant decrease (82%) in the content of 3,4
      dihydoxyphenylacetic acid (DOPAC), a major metabolite of DA, in the NAc of D4R-/-
      mice. Microdialysis studies performed in a region of brain spanning of the dorsal
      Str and NAc showed lower baseline levels of DA and a significant reduction in KCl
      evoked overflow of DA in the D4R-/- mice. Baseline extracellular levels of DOPAC
      and homovanillic acid were also significantly lower in the D4R-/- mice. In vivo
      chronoamperometric recordings of KCl-evoked release of DA also showed decreased
      release of DA in the Str and NAc of the D4R-/- mice. These studies demonstrate a
      role of D4Rs in presynaptic DA regulation and support the hypothesis that
      alterations in D4Rs may lead to diminished DA function.

PMID- 17449108
TI  - Regulation of maternal serum and amniotic fluid cytokine profiles in the mouse:
      possible roles in the onset of labour.
AB  - Murine pregnancy is characterised by marked increases in serum cytokine profiles
      with advancing gestation, but whether these changes reflect concentrations in
      amniotic fluid is unknown. This study therefore profiled 23 cytokines by fluid
      phase multiplex immunoassay of amniotic fluid and serum collected from naturally
      mated mice during mid- and late pregnancy (days 11 and 18, respectively). The
      marked increase in serum profile of many cytokines from days 11 to 18 was not
      reflected in amniotic fluid, wherein most cytokine concentrations were lower on
      day 18. Serum and amniotic fluid cytokine concentrations were largely inversely
      related, indicating separate, localised regulatory mechanisms geared towards the
      maintenance of pregnancy, modulation of immune effector cell function and
      optimisation of fetal development. We suggest that, while maternal systemic
      inflammatory priming prepares the mother for birth, the amniotic compartment
      exhibits a tightly regulated inflammatory quiescence. These findings are
      discussed in relation to the onset of labour, which ultimately results in the
      elevated cytokine amniotic levels traditionally associated with the final stages
      of pregnancy.

PMID- 17449109
TI  - Adolescents in smoking cessation treatment: relationship between externalizing
      symptoms, smoking history and outcome.
AB  - Previous research has indicated a potential bi-directional link between youth
      substance use and externalizing psychiatric comorbidities. We hypothesized that
      the degree of externalizing symptoms predicts the likelihood of successful
      smoking cessation (prolonged abstinence) among adolescent smokers participating
      in a cessation trial. We also explored the association of externalizing symptoms
      with age at smoking initiation. Ninety one adolescents (mean+/-S.D.; age 15.1+/
      1.4 years, cigarettes per day 18.4+/-8.1, Fagerstrom Test for Nicotine Dependence
      7.1+/-1.3) were included. The Child Behavior Checklist/4-18 and Youth Self-Report
      assessed the degree of externalizing symptoms. Regression analysis indicated that
      lower CBCL externalizing scores significantly predicted the likelihood of
      prolonged abstinence. Pearson's correlation analysis indicated a significant
      association of lower externalizing scores with later onset of smoking initiation.
      Our findings highlight the importance of addressing externalizing behaviors in
      adolescent smoking cessation programs.

PMID- 17449110
TI  - Subjective and cardiovascular effects of cocaine during treatment with amantadine
      and baclofen in combination.
AB  - This study assessed the subjective and cardiovascular effects of relevant doses
      of cocaine administration during steady-state treatment of the combination of
      amantadine and baclofen compared to placebo. Participants included 8 healthy,
      male, cocaine-dependent, non-treatment-seeking individuals (age=36.6+/-5.9; 75%
      African American, 25% Caucasian; using cocaine for an average of 15.3+/-6.5
      years). Data were collected prior to and following double-blind intravenous
      administration of 0 mg, 20 mg, and 40 mg of cocaine. Data were collected at
      baseline, following 5 days of treatment with placebo, and again following 5 days
      of treatment with a combination of amantadine 100 mg t.i.d. and baclofen 30 mg
      t.i.d. counterbalanced for order of medication and placebo in a cross-over
      design. Results showed no significant alterations to cardiovascular variables
      (heart rate, systolic and diastolic blood pressure) from treatment using
      combination medication or placebo in the presence of cocaine. Self-rated "desire"
      for cocaine was significantly lower during cocaine administrations while
      participants were receiving treatment with amantadine-baclofen compared to
      infusions while taking placebo medication, although there was no difference in
      the intensity of cocaine-induced euphoria, or reduction in the likelihood to use
      cocaine if given access. Study findings support the safety of the amantadine
      baclofen combination treatment for cocaine dependence.

PMID- 17449111
TI  - Family assessment in early psychosis.
AB  - Some caregiver burden scales designed for chronic schizophrenia may be
      inappropriate for use with families of individuals who are experiencing a first
      episode of psychosis (FEP). The aims of the study were to determine the
      usefulness for FEP families of the Caregiver Burden Inventory (CBI), a scale
      originally designed for use with family members of Alzheimer's patients. The CBI,
      Experience of Caregiving Scale (ECI) and the Psychological General Well-Being
      Scale (PGWB) were administered to the relatives of 113 individuals with a FEP at
      admission to an early psychosis program and again at 6-, 12-, and 24-month follow
      ups. Ratings on the CBI improved significantly over the follow-up period. The CBI
      was significantly associated with the ECI and with ratings of psychological
      distress. The most significant predictor of psychological distress was ratings on
      the CBI and not the severity of symptoms or impaired functioning. Overall, the
      CBI appeared to be a reliable and valid measure for use with FEP families. This
      short and easy to score measure may be useful for families of young people
      presenting with FEP.

PMID- 17449112
TI  - Delayed recall of childhood sexual abuse memories and the awakening rise and
      diurnal pattern of cortisol.
AB  - Traumatic stress associated with childhood sexual abuse (CSA) may result in
      chronic alterations of stress-sensitive neurochemical systems (e.g., the
      hypothalamic-pituitary-adrenal axis and sympathetic-adrenal medullary activity).
      Some authors have suggested that these alterations might help explain why some
      individuals, after a period of inability to remember, demonstrate delayed recall
      of CSA memories (i.e., "recovered" memories). The present study is the first
      study that explored morning cortisol responses and circadian cortisol profiles
      among women with recovered (n=7), repressed (n=8), or continuous (n=6) memories
      of CSA and women without a history of CSA (n=9). Although there were group
      differences in current depression and post-traumatic stress symptoms, we found no
      differences in cortisol awakening response or daytime profile between women
      reporting recovered, repressed, or continuous memories of CSA as compared to
      women without a history of CSA. Implications for neurobiological models intended
      to explain the delayed recall of CSA are discussed.

PMID- 17449113
TI  - Phenotypical characterization of changes in thymus and spleen associated with
      lymphoid depletion in free-ranging harbor porpoises (Phocoena phocoena).
AB  - Harbor porpoises from the North and Baltic Seas exhibit a higher incidence of
      bacterial infections compared to whales from less polluted arctic waters.
      Furthermore, thymic atrophy and splenic depletion, associated with elevated
      concentrations of environmental contaminants, such as polychlorinated biphenyls
      (PCB) and polybrominated diphenyl ether (PBDE) body burdens, have been found in
      wildlife harbor porpoises. Thus, there is currently a debate about the potential
      adverse effect of xenobiotics on the immune system and therefore on the health
      status of this and other marine mammal species. The aim of the present study was
      to characterize phenotypical changes in lymphoid organs of harbor porpoises and
      their possible association with increased disease susceptibility due to an
      impaired immune response in this marine mammal species. Therefore, 29 by-caught
      and stranded harbor porpoises were necropsied and the health status was evaluated
      based upon the severity of main pathological findings. In addition, the
      distribution of CD2-, CD3epsilon-, and CD45R-positive cells as well as B
      lymphocytes, MHC class II-expressing and antigen-presenting cells was determined
      in the thymus and spleen using immunohistochemistry. Thymic atrophy and splenic
      depletion were associated with an impaired health status in investigated whales.
      Phenotypical changes in atrophic thymuses were characterized by a depletion of
      immature cortical thymocytes and medullary B cells. Furthermore, findings in
      depleted spleens were consistent with a loss of peripheral T lymphocytes in the
      periarteriolar lymphoid sheath (PALS). Based upon the results, an altered
      thymopoiesis and impaired cellular immune function cannot be excluded in whales
      with evidence of lymphoid depletion.

PMID- 17449114
TI  - The C3 subtypes are differentially regulated after immunostimulation in rainbow
      trout, but head kidney macrophages do not contribute to C3 transcription.
AB  - The complement system plays key roles in innate and adaptive immunity through
      mediating phagocytosis, chemotaxis and cell lysis. Complement component C3 is a
      central component in the complement cascade and belongs to the acute-phase
      proteins whose synthesis increase immediately upon inflammatory stimuli. The
      liver is the main producer of C3 and it is a well-known fact that the mammalian
      monocyte-macrophage lineage is a major contributor to extrahepatic C3.
      Immunomodulators, such as LPS and beta-glucan, can stimulate complement,
      lysozyme, natural killer cells and antibody responses in fish, thus enhancing the
      resistance to bacterial pathogens and parasitic infections. The aim of this study
      was to assess the effects of LPS and beta-glucan on the expression of
      interleukins (IL-1beta1, IL-1beta2 and IL-6) and the modulated expression of C3
      subtypes (C3-1, C3-3 and C3-4) in the rainbow trout (Oncorhynchus mykiss) using
      real-time RT-PCR. From in vitro studies, we demonstrated that head kidney
      macrophages from rainbow trout and Atlantic salmon showed no basal transcription
      of C3. After immunostimulation, the cells responded by increased levels of ILs,
      but transcription of C3 was not induced. In contrast to the in vitro findings,
      the rainbow trout complement C3 subtypes were differentially regulated 48 h after
      in vivo stimulation with LPS and beta-glucan. These results support the previous
      findings of absence of C3 in macrophages of the spotted wolffish (Anarhichas
      minor) and is the first functional study showing differential regulation of the
      C3 subtypes in any vertebrate.

PMID- 17449115
TI  - Excretory-secretory products from Fasciola hepatica induce eosinophil apoptosis
      by a caspase-dependent mechanism.
AB  - Eosinophils (Eo) are known to be important effector cells in the host defense
      against helminth parasites. Excretory-secretory products (ESP) released by
      helminths have shown wide immunomodulatory properties, such as the induction of
      cellular apoptosis. We investigated the ability of ESP from Fasciola hepatica to
      induce Eo apoptosis. In this work, we observed that ESP induced an early
      apoptosis of rat peritoneal eosinophils and that this phenomenon was time- and
      concentration-dependent. Furthermore, we demonstrated that activation of protein
      tyrosine kinases (TyrK) and caspases were necessary to mediate the Eo apoptosis
      induced by the ESP, and that carbohydrate components present in these antigens
      were involved in this effect. We have described for the first time the ability of
      ESP from F. hepatica to modify the viability of Eo by apoptosis induction.
      Besides that, we have observed Eo apoptosis in the liver of rats 21 days after F.
      hepatica infection. The diminution in Eo survival in early infection could be a
      parasite strategy in order to prevent a host immune response.

PMID- 17449117
TI  - Neurobiology of 50-kHz ultrasonic vocalizations in rats: electrode mapping,
      lesion, and pharmacology studies.
AB  - Fifty-kHz ultrasonic vocalizations have been proposed to reflect a positive
      appetitive affective state in rats, being consistently linked to the positive
      appetitive behavior. In the first study, we examined the brain substrates of 50
      kHz ultrasonic vocalizations (USVs) by using localized electrical stimulation of
      the brain (ESB) at various sites that are known to mediate reward. We found that
      the brain areas that produced ESB-induced 50-kHz calls are the areas that have
      previously been shown to support the most vigorous self-stimulation behavior
      (prefrontal cortex, nucleus accumbens, ventral pallidum, lateral preoptic area,
      lateral hypothalamus, ventral tegmental area, and raphe). Importantly, all
      animals that showed repeatable ESB-induced 50-kHz USVs demonstrated self
      stimulation behavior. In the second study, conditioned place preference was
      assessed following microinjection of the mu-opiate agonist Tyr-D-Ala-Gly-N-methyl
      Phe-Gly-ol (DAMGO) directly into the ventral tegmental area (VTA) at a dose
      previously found to be rewarding. Animals that showed more 50-kHz USVs in
      response to drug injections compared to vehicle injections showed significant
      place preferences, whereas animals that did not show elevated vocalization to
      DAMGO did not show place preference. In experiment 3, we examined the effect of
      VTA electrolytic lesions, 6-OHDA lesions, and the effect of the D1/D2 dopamine
      antagonist flupenthixol (0 and 0.8 mg/kg, i.p.) on 50-kHz ultrasonic
      vocalizations. We found that these manipulations all selectively reduced 50-kHz
      ultrasonic vocalizations, and that these effects could be disassociated from any
      side effects. These data are consistent with the proposition that 50-kHz calls
      are tightly linked to reward in rats and that the neural circuit of 50-kHz calls
      closely overlaps that of ESB self-stimulation reward, drug reward, and the
      mesolimbic dopamine system.

PMID- 17449116
TI  - Sensory feedback control of mammalian vocalizations.
AB  - Somatosensory and auditory feedback mechanisms are dynamic components of the
      vocal motor pattern generator in mammals. This review explores how sensory cues
      arising from central auditory and somatosensory pathways actively guide the
      production of both simple sounds and complex phrases in mammals. While human
      speech is a uniquely sophisticated example of mammalian vocal behavior, other
      mammals can serve as examples of how sensory feedback guides complex vocal
      patterns. Echolocating bats in particular are unique in their absolute dependence
      on voice control for survival: these animals must constantly adjust the acoustic
      and temporal patterns of their orientation sounds to efficiently navigate and
      forage for insects at high speeds under the cover of darkness. Many species of
      bats also utter a broad repertoire of communication sounds. The functional
      neuroanatomy of the bat vocal motor pathway is basically identical to other
      mammals, but the acute significance of sensory feedback in echolocation has made
      this a profitable model system for studying general principles of sensorimotor
      integration with regard to vocalizing. Bats and humans are similar in that they
      both maintain precise control of many different voice parameters, both exhibit a
      similar suite of responses to altered auditory feedback, and for both the
      efficacy of sensory feedback depends upon behavioral context. By comparing
      similarities and differences in the ways sensory feedback influences voice in
      humans and bats, we may shed light on the basic architecture of the mammalian
      vocal motor system and perhaps be able to better distinguish those features of
      human vocal control that evolved uniquely in support of speech and language.

PMID- 17449118
TI  - G418, phleomycin and hygromycin selection of recombinant Trypanosoma brucei
      parasites refractory to long-term in vitro culture.

PMID- 17449120
TI  - An unusual femoral arteriovenous fistula following cardiac catheterization.
AB  - The development of an arteriovenous fistula (AVF) is a rare complication of
      cardiac catheterization. We report a rare case with a femoral AVF following
      cardiac catheterization, originating from the right deep femoral artery and
      eventually draining into the right superficial femoral vein through the
      subcutaneous vein.

PMID- 17449119
TI  - RNA-directed DNA methylation mediated by DRD1 and Pol IVb: a versatile pathway
      for transcriptional gene silencing in plants.
AB  - RNA-directed DNA methylation, which is one of several RNAi-mediated pathways in
      the nucleus, has been highly elaborated in the plant kingdom. RNA-directed DNA
      methylation requires for the most part conventional DNA methyltransferases,
      histone modifying enzymes and RNAi proteins; however, several novel, plant
      specific proteins that are essential for this process have been identified
      recently. DRD1 (defective in RNA-directed DNA methylation) is a putative
      SWI2/SNF2-like chromatin remodelling protein; DRD2 and DRD3 (renamed NRPD2a and
      NRPD1b, respectively) are subunits of Pol IVb, a putative RNA polymerase found
      only in plants. Interestingly, DRD1 and Pol IVb appear to be required not only
      for RNA-directed de novo methylation, but also for full erasure of methylation
      when the RNA trigger is withdrawn. These proteins thus have the potential to
      facilitate dynamic regulation of DNA methylation. Prominent targets of RNA
      directed DNA methylation in the Arabidopsis thaliana genome include
      retrotransposon long terminal repeats (LTRs), which have bidirectional
      promoter/enhancer activities, and other types of intergenic transposons and
      repeats. Intergenic solitary LTRs that are targeted for reversible methylation by
      the DRD1/Pol IVb pathway can potentially act as switches or rheostats for
      neighboring plant genes. The resulting alterations in gene expression patterns
      may promote physiological flexibility and adaptation to the environment.

PMID- 17449121
TI  - Ventricular tachycardia in a man with spontaneous coronary artery dissection.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare cause of acute ischemic
      coronary events. It is more prevalent in young women, particularly in the
      peripartum period. In men it is an extremely rare cause. We described the
      clinical course of a patient, man, presenting pain chest and ventricular
      malignant arrhythmias. Four days after admission the patient underwent coronary
      angiography, showing a large SCAD. After this, he had undergone coronary artery
      bypass surgery. He presented an angiography and clinical resolution and he was
      still asymptomatic at a 6-month clinical follow up. Pathophysiologic aspects and
      treatment options of spontaneous coronary artery dissection are discussed.

PMID- 17449122
TI  - Objective quantification of global and regional left ventricular systolic
      function by endocardial tracking of contrast echocardiographic sequences.
AB  - BACKGROUND: Echocardiographic assessment of LV wall motion is still most
      frequently done visually. This study was designed to validate a new system for
      semi-automatic quantification of global and regional LV systolic function from
      contrast-enhanced cross-sectional echocardiograms. METHODS: Measurements of LV
      volumes were validated in 50 patients using magnetic resonance (MR) as reference.
      The regional identification of the endocardial boundary was validated frame-by
      frame against the visually identified border in another 27 patients. Finally, the
      applicability of the system for quantifying stress-echocardiographic exams was
      assessed in 52 patients undergoing dobutamine interventions. Echocardiographic
      sequences were digitally processed using custom-built algorithms, based on local
      phase feature descriptors, deformable contour fitting, and prospective training.
      RESULTS: Compared to MR, the tracing system showed reasonable accuracy, with
      relative errors for end-diastolic volume, end-systolic volume, and EF of 21+/
      20%, 27+/-33%, and--4+/-18%, respectively. Regional agreement of the
      instantaneous contours with visually traced borders was within the limits of
      visual reproducibility. The system was suitable for tracking stress-echo studies
      from all patients except two (96%). Quantification of regional radial shortening
      allowed to discriminate segments showing an abnormal regional wall motion with an
      overall area under the ROC curve of 0.87. CONCLUSIONS: A reliable and accurate
      quantification of LV systolic function can be obtained by processing contrast
      echocardiograms. Values of LV volumes, ejection fraction, and regional
      endocardial shortening adequately correlate with currently available reference
      methods. Readily applicable to baseline and stress studies, endocardial tracking
      techniques increase the reliability of echocardiography for the assessment of
      global and regional systolic function.

PMID- 17449123
TI  - Interoceptive awareness, anxiety and cardiovascular reactivity to isometric
      exercise.
AB  - The present study was designed to investigate the relation between cardiovascular
      reactivity, trait anxiety and the interoceptive awareness. Eighteen male subjects
      underwent a heartbeat perception task and performed an isometric handgrip
      exercise. Subjects with high reactivity showed a higher degree of interoceptive
      awareness and trait anxiety suggesting that a habitually increased sympathetic
      outflow might be one variable contributing to the establishment of high
      interoceptive awareness and trait anxiety.

PMID- 17449124
TI  - Mismatch negativity impairment associated with alcohol consumption in chronic
      alcoholics: a scalp current density study.
AB  - Previous studies, based on amplitude and latency measurements of auditory event
      related brain potentials, yielded inconclusive results about the status of
      mismatch negativity (MMN) in chronic alcoholics. The present study explores scalp
      current density (SCD) dynamics during MMN latency range in alcoholics, and
      correlates electrical SCD results with clinical data of the patients. SCD was
      computed from 30 electrodes in 16 abstinent chronic alcoholics and 16 healthy
      control volunteers in a paradigm on MMN elicited by duration changes. Reduced
      activity was observed in left frontal and right anterior and posterior temporal
      areas during MMN in alcoholics. Alcohol consumption correlated negatively with
      SCD intensity in these regions. Delayed activation was observed in the left
      posterior temporal area in the patients. Alcohol abstinence duration correlated
      positively with SCD intensity in this region. These results point to an
      impairment of automatic brain processing mechanisms associated with auditory
      change detection in chronic alcoholism. The present results suggest a
      reorganization of the computational neurodynamics of automatic auditory change
      detection linked to the amount of alcohol consumed in abstinent chronic
      alcoholics.

PMID- 17449126
TI  - Surveying cereal-infecting geminiviruses in Germany--diagnostics and direct
      sequencing using rolling circle amplification.
AB  - Geminiviruses have spread in German cereal crops during the last few years. In
      order to identify and classify them, we have compared conventional techniques
      (enzyme-linked immunosorbent assays, polymerase chain reaction, bacterial
      cloning, and sequencing) with a newly developed method which uses rolling circle
      amplification (RCA), restriction fragment length polymorphism (RFLP), and direct
      sequencing without a bacterial cloning step. Whereas immunological methods
      utilising polyclonal antibodies were reliable for detection of geminiviruses,
      they did not discriminate between different German mastrevirus species, in
      contrast to RCA/RFLP. Direct sequencing gave high fidelity results with the same
      quality as conventional cloning and sequencing but with significantly reduced
      effort and costs. Based on a survey of field-derived cereal samples and on DNA
      sequences of distinct virus isolates we propose two new mastrevirus species, to
      be named Barley dwarf virus (BDV), and Oat dwarf virus (ODV) according to
      sequence differences and host range studies. The results show the applicability
      of RCA-based techniques for field studies and the possibility of sequencing a
      geminiviral genome without cloning. This approach will accelerate genomics
      studies of all viruses with small circular DNA genomes. In addition, RCA proves
      to be a reliable technique allowing for the detection of new geminivirus species
      as it does not depend on the knowledge of specific primers.

PMID- 17449125
TI  - The in vitro antibacterial activity of dietary spice and medicinal herb extracts.
AB  - The in vitro antibacterial activities of a total of 46 extracts from dietary
      spices and medicinal herbs were investigated by agar-well diffusion method
      against five foodborne bacteria (Bacillus cereus, Listeria monocytogenes,
      Staphylococcus aureus, Escherichia coli, and Salmonella anatum). Their total
      phenolic contents were also evaluated. Many herb and spice extracts contained
      high levels of phenolics and exhibited antibacterial activity against foodborne
      pathogens. Gram-positive bacteria were generally more sensitive to the tested
      extracts than Gram-negative ones. S. aureus was the most sensitive, while E. coli
      was the most resistant. There were highly positive relationships (R(2)=0.73-0.93)
      between antibacterial activities and phenolic content of the tested extracts
      against each bacterium. This suggested that the antibacterial activity of the
      tested extracts was closely associated with their phenolic constituents.

PMID- 17449127
TI  - Isolation of recombinant type 2 vaccine-derived poliovirus (VDPV) from a Nigerian
      child.
AB  - A type 2 vaccine-derived poliovirus (VDPV), differing from Sabin 2 at 2.5%
      (22/903) of VP1 nucleotide (nt) positions, was isolated from an incompletely
      immunized 21-month-old Nigerian child who developed acute flaccid paralysis in
      2002. Sequences upstream of nt position 620 (within the 5'-untranslated region
      [5'-UTR]) and downstream of nt position 5840 (in the 3C(pro) region) were derived
      from species C enteroviruses unrelated to the oral poliovirus vaccine (OPV)
      strains. The two substitutions associated with the attenuated phenotype had
      either recombined out (A(481)-->G in the 5'-UTR) or reverted (Ile(143)-->Thr in
      VP1). The VDPV isolate had lost the temperature sensitive phenotype of Sabin 2
      and it was antigenically distinct from the parental OPV strain, having amino acid
      substitutions in or near neutralizing antigenic sites 1 and 3. The date of the
      initiating OPV dose, calculated from the number of synonymous substitutions in
      the capsid region, was estimated to be approximately 16 to 18 months before onset
      of paralysis, a finding inconsistent with the most recent mass OPV campaign
      (conducted 12 days before onset of paralysis) as being the source of infection.
      Although no related type 2 VDPVs were detected in Nigeria or elsewhere, the VDPV
      was found in an area where conditions favor VDPV emergence and spread.

PMID- 17449128
TI  - Hepatitis C virus genetic variability in patients undergoing antiviral therapy.
AB  - Hepatitis C virus (HCV) has been the subject of intense research and clinical
      investigations due to its worldwide prevalence and major role in chronic liver
      disease. Like most RNA viruses, HCV circulates in vivo as a complex population of
      different but closely related viral variants, commonly referred to as a
      quasispecies. Recent studies suggest that ribavirin might exert an antiviral
      effect against HCV through both mutagenic effect and an impairment of RNA
      replication. The introduction of alpha interferon (IFN-alpha) plus ribavirin
      combination therapy was an important breakthrough in the treatment of chronic HCV
      infection. However, the rate of sustained virological response is still
      unsatisfactory, particularly in patients infected with HCV genotype 1. Viral
      persistence, a hallmark of HCV, may result from a dynamic control of the host
      response by the virus. In children with chronic HCV infection, the viral
      population is initially highly homogeneous, but diversifies during prolonged
      infection which seems to be a common event during chronic hepatitis C in
      childhood. Coinfection of human immunodeficiency virus 1 (HIV-1) patients by HCV
      can complicate the treatment of these patients with highly active antiretroviral
      therapy (HAART). HIV coinfection is associated with a decrease of HCV
      quasispecies variability, which appears to be reversed by effective HAART.

PMID- 17449129
TI  - The isokinetic assessment of peripheral muscle function in patients with coronary
      artery disease: correlations with cardiorespiratory capacity.
AB  - OBJECTIVE: We aimed to determine whether diminished cardiorespiratory capacity in
      patients with coronary artery disease (CAD) is accompanied by impaired skeletal
      muscle function as measured by isokinetic dynamometry. We also evaluated the
      correlation between isokinetic strength and aerobic capacity in these patients.
      MATERIALS AND METHODS: Fifteen CAD patients and 15 age-matched healthy subjects
      (mean age 60+/-6 vs. 57+/-3.5 years) underwent maximal laboratory exercise
      testing, a 6-min walking test and an assessment of peripheral skeletal muscle
      function by use of an isokinetic apparatus. Quadricep and hamstring function was
      tested at two angular velocities, 150 and 180 degrees s(-1) with simultaneous
      electrocardiography monitoring. The cardiorespiratory and mechanical parameters
      (VO(2), ventilatory threshold [VT], heart rate [HR], and power) were measured at
      VT and at maximal effort. RESULTS: Quadricep and hamstring peak torque was
      impaired in CAD patients, with quadriceps peak torque at 180 degrees being 71.13
      +/- 14 vs. 91.13 +/- 23 Nm (P<0.01) and hamstring peak torque 46.50+/-10 vs.
      59.86+/-12 Nm (P<0.01). CAD subjects presented a deficient aerobic capacity as
      compared with the healthy subjects at maximal effort. At VT, the VO(2),
      ventilation, and HR were significantly lower in CAD patients, at 13.77+/-2.33 vs.
      17.08+/-3.59 ml min(-1) kg(-1) (P<0.05), 29.64 +/- 664 vs. 37.76 +/- 7.2 ml min(
      1) (P<0.05), and 86+/-14 vs. 111+/-15 beats min(-1) (P=0.001), respectively. The
      6-min walking distance was significantly shorter for CAD patients than healthy
      subjects (425.93+/-52.77 vs. 551.46 +/- 57.94 m; P<0.01). In CAD patients
      quadriceps and hamstring strength was not correlated with VO(2) at maximal effort
      and at VT. Total distance walked during the 6-min walk and VO(2)max were
      correlated (r=0.869; P<0.001) but not at VT. CONCLUSION: CAD patients showed
      impaired cardiorespiratory capacity accompanied by increased muscle fatigability
      as compared with healthy subjects. An isokinetic muscle assessment in these
      patients must be achieved systematically and seems to have value in
      cardiovascular rehabilitation.

PMID- 17449130
TI  - Impaired metabolism-secretion coupling in pancreatic beta-cells: role of
      determinants of mitochondrial ATP production.
AB  - Glucose-induced insulin secretion from beta-cells is often impaired in diabetic
      condition and by exposure to diabetogenic pharmacological agents. In pancreatic
      beta-cells, intracellular glucose metabolism regulates exocytosis of insulin
      granules, according to metabolism-secretion coupling in which glucose-induced
      mitochondrial ATP production plays an essential role. Impaired glucose-induced
      insulin secretion often results from impaired glucose-induced ATP elevation in
      beta-cells. Mitochondrial ATP production is driven by the proton-motive force
      including mitochondrial membrane potential (DeltaPsi(m)) generated by the
      electron transport chain. These electrons are derived from reducing equivalents,
      generated in the Krebs cycle and transferred from cytosol by the shuttles. Here,
      roles of the determinants of mitochondrial ATP production in impaired glucose
      induced insulin secretion are discussed. Cytosolic alkalization, H(+) leak in the
      inner membrane by uncoupler (e.g. free fatty acid exposure), decrease in the
      supply of electron donors including NADH and FADH(2) to the respiratory chain,
      and endogenous mitochondrial ROS (e.g. Na(+)/K(+)-ATPase inhibition) all reduce
      hyperpolarlization of DeltaPsi(m) and ATP production, causing decresed glucose
      induced insulin release. The decrease in the supply of NADH and FADH(2) to the
      respiratory chain derives from impairments in glucose metabolism including
      glycolysis (e.g. MODY2 and exposure to NO) and the shuttles (e.g. diabetic state
      and exposure to ketone body).

PMID- 17449131
TI  - C-reactive protein and features of metabolic syndrome in Brazilian women with
      previous gestational diabetes.
AB  - OBJECTIVE: C-reactive protein (CRP), an inflammatory biomarker, has been
      associated with the development of diabetes. Gestational diabetes (GDM) predicts
      type 2 diabetes (T2DM) and may be part of the metabolic syndrome (MS). Few
      studies have examined the association of CRP, MS and diabetes in women with
      previous GDM. RESEARCH DESIGN AND METHODS: Women with previous GDM (n=70) and
      randomly sampled women without previous GDM (n=108) from the one center of the
      Brazilian Study of Gestational Diabetes participated in the study after 6 years
      of index pregnancy. Oral glucose tolerance test and anthropometry were performed.
      CRP levels were measured by the nephelometry. The MS was defined by the ATPIII
      criteria. RESULTS: There was significant positive linear correlation between CRP
      levels, fasting insulin (R=0.053) and HOMA IR (0.048) in previous GDM. Mean CRP
      levels were significantly higher in previous GDM group with abdominal obesity
      (1.227 95% CI 0.871-1.584 versus 0.597, 95% CI 0.378-0.817; p=0.001) and abnormal
      glucose tolerance (1.168 95% CI 0.784-1.552 versus 0.657 95% CI 0.455-0.859,
      p=0.012). There were differences when considering the presence of different MS
      features, once the previous GDM group reported a significantly higher number of
      women with low HDL (74.3% versus 55.6%, p=0.016) and abnormal glucose tolerance
      (45.7% versus 25%, p=0.005) than the group without GDM. On average, the CRP
      levels were significantly higher in women with previous GDM and MS (0.918 95% CI
      0.569; 1.268 versus 0.524 95% CI 0.373; 0.675, p=0.044) than the control group.
      CONCLUSIONS: The data suggests that the presence of MS in women with previous GDM
      is associated with high levels of CRP.

PMID- 17449132
TI  - Role of PDX-1 and MafA as a potential therapeutic target for diabetes.
AB  - Pancreatic and duodenal homeobox factor-1 (PDX-1) plays a crucial role in
      pancreas development, beta-cell differentiation, and maintaining mature beta-cell
      function. During pancreas development, PDX-1 expression is maintained in
      precursor cells, and later it becomes restricted to beta-cells. In mature beta
      cells, PDX-1 regulates gene expression of various beta-cell-related factors
      including insulin. Also, PDX-1 has potency to induce insulin-producing cells from
      non-beta-cells in various tissues, and PDX-1-VP16 fusion protein more efficiently
      induces insulin-producing cells, especially in the presence of NeuroD or Ngn3.
      MafA is a recently isolated beta-cell-specific transcription factor which
      functions as a potent activator of insulin gene transcription. During pancreas
      development, MafA expression is first detected at the beginning of the principal
      phase of insulin-producing cell production. Furthermore, MafA markedly enhances
      insulin gene promoter activity and ameliorates glucose tolerance in diabetic
      mice, especially in the presence of PDX-1 and NeuroD. Taken together, PDX-1 and
      MafA play a crucial role in inducing surrogate beta-cells and could be a
      therapeutic target for diabetes.

PMID- 17449134
TI  - Policy and regulatory responses to dual practice in the health sector.
AB  - Physician dual practice is a widespread phenomenon which has implications for the
      equity, efficiency and quality of health care provision. Central to the analysis
      of physician dual practice is the trade-off between its benefits and costs, as
      well as the convenience of regulating it to undermine its adverse consequences.
      In this paper, we study and analyze different governmental responses to this
      activity. We find that internationally, there are wide variations in how
      governments tackle this issue. While some governments fully prohibit this
      practice, others regulate or restrict dual job holding with different intensities
      and regulatory instruments. The measures implemented include limiting the income
      physicians can earn through dual job holding, offering work benefits to
      physicians in exchange for their working exclusively in the public sector,
      raising public salaries, and allowing physicians to perform private practice at
      public facilities. We present the pros and cons of each of these alternatives and
      show how the health care market and institutional arrangements are crucial for
      the design and implementation of each of these strategies. The paper also
      identifies the need for empirical evidence on the effect of different government
      strategies on dual practice.

PMID- 17449133
TI  - Re-evaluation of the penicillamine challenge test in the diagnosis of Wilson's
      disease in children.
AB  - BACKGROUNDS/AIMS: A urinary copper (Cu) >25 micromol/24 h following penicillamine
      had a reported specificity of 98.2% and sensitivity of 88.2% in diagnosing
      Wilson's disease (WD). We have re-evaluated this test. Ninety-eight subjects were
      studied at presentation. METHODS: Thirty-eight (19 girls, 19 boys; median age
      10.3 years; range 5-16 years) had an ultimate diagnosis of WD. Sixty (24 girls,
      36 boys; median age 10.1, range 2.3-15 years) had other liver disorders. Urinary
      Cu was estimated for 24h before (basal Cu) and for 24h whilst giving
      penicillamine 500 mg orally 12 hourly x 2 (post-penicillamine Cu). RESULTS: Both
      basal Cu and post-penicillamine Cu differed significantly between WD patients and
      controls (basal Cu: median 6.5 micromol/24 h, range 0.9-109 micromol/24 h, versus
      median: 0.8 micromol/24 h, range 0.1-19.5, p<0.0001; post-penicillamine Cu:
      median 36.9 micromol/24 h, range 1.98-219 micromol/24 h, versus median 12.35
      micromol/24 h, range 0.5-49.8 micromol/24 h, p<0.0001). A post-penicillamine Cu
      >25 micromol/24 h was observed in 29/38 patients with WD and in 4/60 controls.
      25/38 WD patients were symptomatic. Twenty-three of these and 6/13 asymptomatic
      siblings had a positive test. The test had a sensitivity of 76% (95% confidence
      interval [CI], 59.8-88.6%) and a specificity of 93% (95% CI, 83.8-98.2%).
      Sensitivity was better in symptomatic patients (92%, [95% CI; 74-99%]) than
      asymptomatic (46%, [95% CI; 19.2-74.9%]). CONCLUSIONS: This test is valuable in
      the diagnosis of WD with active liver disease, but is unreliable to exclude the
      diagnosis in asymptomatic siblings.

PMID- 17449135
TI  - The politics of global immunization initiatives: can we learn from research on
      global environmental issues?
AB  - The number of institutions, representing different groups of stakeholders and
      organizations, aiming to coordinate global health policy is on the rise. Yet, as
      each have distinct interests and priorities, the political dimension becomes an
      important factor in understanding how institutions work, and how the coordination
      at the global level affects implementation in countries. This is already a topic
      for research on global environmental cooperation, inciting the question if one
      can transfer their analytical framework to the health field. This paper combines
      a presentation of lessons from research on environmental regimes with a review of
      global immunization policies and initiatives in order to explore that
      possibility. The paper describes cooperation on vaccines and immunization
      according the concepts of institutions and regimes, as defined by international
      relations research. This description emphasizes efforts to fulfill transnational
      agreements on objectives, the different ways stakeholders organize and the
      dynamics of such arrangements. An account of the research practice on global
      environmental cooperation leads to a discussion of how one could adapt the
      analytical framework. The paper makes the case for the development of a research
      program, where the analytical approach is modified to account for the interaction
      between technology production and public-led institutions. The conclusion
      proposes a number of entry points to research that have already yielded policy
      relevant knowledge in the environmental field. These include the formation of new
      institutions, the contribution of institutional design to effective
      implementation, and the interplay between vaccine initiatives and other global
      institutions.

PMID- 17449136
TI  - Chromatin regulation and sex determination in Caenorhabditis elegans.
AB  - Glioma-associated oncogene (GLI) transcription factors function downstream of the
      hedgehog signal transduction pathway to regulate the development of many animals.
      Although the nematode Caenorhabditis elegans lacks a hedgehog pathway, it does
      have a GLI protein that represses male development in favor of hermaphrodite
      development. As we discuss here, recent findings implicate two conserved
      transcription-repressor complexes in the repression of male-specific genes. This
      research indicates a possible conserved role for these complexes in either GLI
      directed gene repression or sex determination.

PMID- 17449138
TI  - Serum tumor markers as predictors for survival in advanced non-small cell lung
      cancer patients treated with gefitinib.
AB  - BACKGROUND: Though the imaging-based response (IBR) is the most frequently used
      index of the therapeutic effect in cancer patients, an index based on serum tumor
      markers might prove to be useful, especially in patients without measurable
      tumors. METHODS: Paired pre- and post-treatment serum tumor markers (CEA, CA-125,
      and CA-199) were measured in 89 of 100 registered non-small cell lung cancer
      (NSCLC) patients who received gefitinib. Correlation and agreement analyses
      between the IBR at the 8th week and the tumor marker response (TMR) at the 4th or
      the 8th week were performed in patients with measurable lesions (n=68). Analysis
      of survival in relation to TMR was performed in all patients and in patients with
      no measurable lesions (n=21). RESULTS: IBR was closely correlated with individual
      tumor marker responses and the response of all 3 markers combined at 4 weeks (P
      values ranged from <0.001 to 0.002). The agreements were also significant (P
      values ranged from 0.001 to 0.004). In the whole group, 4-week TMR was predictive
      for progression-free survival (P values ranged from <0.0001 to 0.0086). In
      patients without measurable lesions, differences in progression-free survival and
      overall survival were closely correlated with the 4-week CA-125 response, CA-199
      response, and TMR(overall) (P values ranged from 0.0002 to 0.0399). However, the
      correlation between the 8-week TMR and either IBR or survival was not
      significant. CONCLUSIONS: In gefitinib-treated NSCLC patients, correlation was
      good between 4-week TMR and IBR. Four-week TMR was predictive for survival. TMR
      may serve as a tool for assessing the gefitinib response in patients without
      measurable lesions.

PMID- 17449139
TI  - Prion protein resides in membrane microclusters of the immunological synapse
      during lymphocyte activation.
AB  - Expression of prion protein (PrP) has been reported for a variety of cell types
      including neuronal cells, haematopoietic stem cells, antigen-presenting cells, as
      well as lymphocytes. However, besides this widespread occurrence little is known
      about the physiological roles exhibited by this enigmatic protein. In this study,
      the contribution of PrP to the classical T-lymphocyte activation process was
      characterized by clustering the T-cell receptor component CD3epsilon as well as
      PrP with soluble and surface-immobilized antibodies, respectively. We present
      evidence that PrP is a component of signaling structures recently described as
      plasma membrane microclusters established during T-lymphocyte activation. The
      formation of immunological synapses, however, did not depend on the presence of
      PrP as proven by siRNA knockdown experiments, indicating very subtle
      physiological roles of PrP in vivo within the immune system.

PMID- 17449137
TI  - RNAi therapeutics: principles, prospects and challenges.
AB  - RNA interference (RNAi) was discovered less than a decade ago and already there
      are human clinical trials in progress or planned. A major advantage of RNAi
      versus other antisense based approaches for therapeutic applications is that it
      utilizes cellular machinery that efficiently allows targeting of complementary
      transcripts, often resulting in highly potent down-regulation of gene expression.
      Despite the excitement about this remarkable biological process for sequence
      specific gene regulation, there are a number of hurdles and concerns that must be
      overcome prior to making RNAi a real therapeutic modality, which include off
      target effects, triggering of type I interferon responses, and effective delivery
      in vivo. This review discusses mechanistic aspects of RNAi, the potential problem
      areas and solutions and therapeutic applications. It is anticipated that RNAi
      will be a major therapeutic modality within the next several years, and clearly
      warrants intense investigation to fully understand the mechanisms involved.

PMID- 17449140
TI  - Localization of Gts1p in cortical actin patches of yeast and its possible role in
      endocytosis.
AB  - Herein we report that Gts1p fused with green-fluorescent protein (GFP) is
      localized in the cortical actin patch besides nuclei in yeast and the cortical
      Gts1p changed its position together with the patch depending on the cell-cycle
      phase, while nuclear Gts1p accumulated predominantly in the budding phase.
      Whereas Gts1p does not directly bind to actin, it associated mainly with the
      actin-associated protein Pan1p. In the GTS1-deleted transformant gts1Delta, the
      number of cells containing either a fragmented vacuole or an enlarged single
      central vacuole increased and the uptake of the hydrophilic dye Lucifer yellow
      (LY) in the vacuole decreased. Further, gts1Delta transformed with a mutant Gts1p
      having two cysteine-to-alanine substitutions in a zinc finger resembling that of
      GTPase-activating proteins of ADP-ribosylation factors (ARF-GAP) neither
      recovered the LY uptake unlike gts1Delta transformed with the wild-type GTS1, nor
      reduced the average size of central vacuoles as much as the latter did. These
      results suggested that Gts1p in the actin patch is involved in the fluid-phase
      endocytosis and membrane trafficking for vacuole formation and that the putative
      ARF-GAP domain in Gts1p plays an important role in these functions.

PMID- 17449141
TI  - Comparison of four clinical prediction rules for estimating risk in heart
      failure.
AB  - STUDY OBJECTIVE: We examine the performance of 4 clinical prediction rules
      prognostic of short-term fatal and hospital-based nonfatal outcomes in heart
      failure patients. METHODS: We used a retrospective cohort of 33,533 adult
      patients admitted to Pennsylvania hospitals in 1999 with a diagnosis of heart
      failure. We stratified patients into risk categories defined by each clinical
      prediction rule. We assessed prognostic accuracy according to sensitivity and
      specificity and compared discriminatory power according to area under the
      receiver operating characteristic (ROC) curves. The outcomes were inpatient
      death, 30-day mortality, and death or serious medical complications before
      hospital discharge. RESULTS: The 4 rules each created risk groups of various
      proportions and frequencies of outcomes. The proportion of patients assigned to
      the lowest risk group ranged from 13.3% to 73.0%. The rates of inpatient death or
      complications in the lowest risk group ranged from 6.7% to 9.2%, and 30-day death
      rates varied from 1.7% to 6.0%. Patients categorized at the highest risk of death
      or complication demonstrated similar variability. The area under the ROC curve
      for inpatient death and complications differed only slightly among rules (0.58 to
      0.62). The area under the ROC curve for fatal outcomes tended to be higher and
      differed among rules (0.59 to 0.74) CONCLUSION: Current acute heart failure
      prediction rules offer varying ability to predict short-term death or serious
      outcomes. Although each creates a risk gradient, differences in risk-group
      proportions and outcome frequencies should drive rule selection or use in
      clinical practice.

PMID- 17449142
TI  - Evidence-based emergency medicine/critically appraised topic. Thrombolytic
      therapy for submassive pulmonary embolism?
AB  - STUDY OBJECTIVE: The purpose of this review was to determine the effectiveness of
      adding thrombolytics to standard heparin therapy for treatment of submassive
      pulmonary embolism. Patients with submassive pulmonary embolism were considered
      to be those with evidence of right ventricular dysfunction but without
      hemodynamic instability. METHODS: We searched for trials comparing thrombolytics
      to heparin in the Cochrane Central Register of Controlled Trials, MEDLINE, and
      EMBASE. We included only studies assessing the effectiveness of thrombolytic
      therapy for submassive pulmonary embolism and reported the patient-important
      outcomes of mortality, recurrent pulmonary embolism, and major hemorrhage.
      RESULTS: Two randomized trials met the inclusion criteria; one with a total of
      256 patients presenting with submassive pulmonary embolism and the other trial
      including a subgroup of 46 patients with submassive pulmonary embolism. In the
      larger study, the relative risk (RR) for mortality, recurrent pulmonary embolism,
      and major hemorrhage was 1.56 (95% confidence interval [CI] 0.36 to 6.83), 1.17
      (95% CI 0.30 to 4.57), and 0.23 (95% CI 0.03 to 1.97), respectively. Our post hoc
      subgroup analysis of the smaller trial identified 2 deaths and 5 patients with
      recurrent pulmonary embolism among 23 controls, whereas none of the 23 patients
      randomized to thrombolytics died or had recurrent pulmonary embolism. None of
      these findings were statistically significant. CONCLUSION: Results of randomized
      trials comparing the addition of thrombolytic therapy to standard heparin therapy
      for treatment of submassive pulmonary embolism fail to show any significant
      differences in clinically important outcomes.

PMID- 17449143
TI  - High doses of ultraviolet-C irradiation increases vasoactive intestinal
      contractor/endothelin-2 expression in keratinocytes of the newborn mouse
      epidermis.
AB  - We examined the expression profiles of vasoactive intestinal
      contractor/endothelin-2 (VIC/ET-2) at both gene and peptide level in skin
      irradiated with different ultraviolet wavelengths. We found that VIC/ET-2 gene
      expression is sensitive only to ultraviolet-C (UVC) irradiation and has an
      immediate response. These results provide direct evidence that high doses of UVC
      irradiation induce an increase in gene expression and protein production of
      VIC/ET-2 and endothelin (ET) receptors in a dose-dependent manner in epidermal
      keratinocytes. We suggest that VIC/ET-2 can play an essential role in the
      maintenance, protection and hyperpigmentation of the epidermis exposed to UVC
      irradiation from artificial or natural sources.

PMID- 17449144
TI  - Professional nursing values among baccalaureate nursing students in Hong Kong.
AB  - The development of a nursing code of professional conduct is to guide nurses to
      make appropriate clinical decision, in particular when facing ethical dilemma. It
      is of paramount importance that nurse educators understand baccalaureate nursing
      students' perceptions of the importance of the code of professional conduct and
      the level of difficulties in implementing this code while preparing them for
      future practicing nurses. The Code of Professional Conduct in Hong Kong has been
      developed to guide nursing practice for over two decades. Nevertheless, no study
      has examined Hong Kong baccalaureate nursing students' perception about this
      professional code. The aim of this paper was to examine the perceptions of 263
      baccalaureate nursing students about this professional code using a cross
      sectional survey design. The results indicated that most items in the
      professional code were rated as important and "provide safe and competent care"
      was rated as the most important one. A few areas that the students perceived as
      difficult to implement were discussed and future research was recommended. The
      significant differences identified among students from different years of study
      also highlighted areas for consideration in planning educational program to
      further equip students with the ability to deal with challenges in professional
      practice.

PMID- 17449145
TI  - Enrolled nurse to registered nurse: is there a link between initial educational
      preparation and course completion?
AB  - There is a shortage of registered nurses (RN) globally and equally in rural areas
      of Australia. The sparsely populated areas of rural Australia prompted the
      development of an external-mode EN-to-RN pathway course for enrolled nurses (EN)
      who want to complete a nursing degree. However, the awarding of advanced standing
      for EN clinical experience, regardless of educational background, is a new
      initiative that needs to be evaluated. Hence, this paper reports on the link
      between initial EN educational preparation and its impact on course completion.
      This exploratory correlation study used existing course data from four cohorts
      between 2000 and 2003. The comparisons included educational background, years of
      experience, and location of the EN-to-RN students. Significant differences were
      not found between rural and metropolitan students who completed or who withdrew
      from the course. Logistic regression analysis indicated that ENs in this sample
      with a hospital-based certificate rather than a technical college qualification
      were more likely to complete the course: Location and years of experience as an
      EN did not contribute significantly to course completion. The findings provide
      support for the same recognition of prior learning, regardless of educational
      background, for ENs entering a bachelor level nursing degree. The findings have
      relevance for Australia and other countries with similar challenges for ENs who
      want to become RNs without relocating to a city.

PMID- 17449146
TI  - Evaluation of selected outcomes of an accelerated nursing degree program.
AB  - Accelerated or condensed programs in nursing have gained popularity over the last
      10 years in Canada. They are designed to accommodate the learning needs of a
      special pool of learners with prior university education. These learners have
      expectations, abilities, and skills different from students in basic
      baccalaureate programs and so require instruction to suit their background. While
      accelerated programs have proliferated, there is little published evidence as to
      the actual number in Canada or on their effectiveness in preparing beginning
      practitioners who can meet the demands of the workplace. In this paper, the
      authors discuss selected outcomes of a pilot project wherein an accelerated
      option was examined as a feasible avenue for the education of Canadian
      professional nurses. Evaluation during and following the project was an integral
      component to contribute to an evidence base for nursing education decisions. Data
      were collected from two student cohorts and multiple stakeholders including
      faculty, employers, and nurse co-workers. Data were elicited on many variables
      but only four are addressed here. These are: scores on the national licensure
      examination, competency-to-practice rankings, student and employer perceptions of
      preparedness for practice, and manageability of students' stress levels during
      the program. The paper focuses on the findings pertaining to each variable and
      the lessons learned.

PMID- 17449147
TI  - Effect of different lipid emulsions on the immunological function in humans: a
      systematic review with meta-analysis.
AB  - BACKGROUND & AIMS: Reports regarding the pro- or anti-inflammatory effects of
      lipid emulsion used in parenteral nutrition are conflicting. Aim was to assess
      the effect of different intravenous lipid emulsions on immunological function in
      humans. METHODS: We performed a computerized bibliographic search, searched
      reference lists in trial reports, hand-searched journals and contacted experts in
      the field. Randomized clinical trials evaluating the immunological effects of
      different parenteral lipid emulsions were included. Three authors independently
      performed data extraction, statistical processes were performed by two experts.
      Immunological parameters were classified by two immunologists as marker of
      improved or worsened immune function. A meta-analysis with standardized effect
      size estimation was performed for the comparison between long-chain triglycerides
      vs. glucose or other fat emulsions. RESULTS: Of 682 assessed studies, 120
      compared the immunological effects of intravenously applied lipid emulsions. Of
      30 randomized trials, 14 were included in the meta-analysis. None of the lipid
      regimens showed any clear effect on the evolution of the immunological status or
      mortality in humans. Length of hospital stay and stay in the intensive care unit
      could not be evaluated. CONCLUSION: We found no evidence that lipid emulsions and
      in particular those containing long-chain triglycerides have an unfavorable
      effect on immune function.

PMID- 17449148
TI  - Update on non-alcoholic fatty liver disease in children.
AB  - Non-alcoholic fatty liver disease (NAFLD) is probably the most common cause of
      liver disease in the pediatric community. It is closely associated with obesity
      and insulin resistance. NAFLD may lead to non-alcoholic steatohepatitis (NASH).
      Although NASH is a prerequisite for the definition of NAFLD in adults and
      children, distinct differences are often apparent in the extent or location of
      fat, inflammation and fibrosis. Confirmation of the diagnosis of NAFLD can
      usually be achieved by imaging studies; however, staging the disease requires a
      liver biopsy. Current treatment relies on weight loss and exercise, although
      various insulin-sensitizing agents, antioxidants and medications appear
      promising. The aim of this review is to summarize what is known about pediatric
      NAFLD in terms of prevalence, pathogenesis, diagnosis, histology and treatment.

PMID- 17449149
TI  - Workshop on vaccine pressure and Neisseria meningitidis, Annecy, France, 9-11
      March 2005.
AB  - A 3-day workshop, "Vaccine pressure and Neisseria meningitidis", was held in
      Annecy, France, 9-11 March 2005, to summarize the current state of knowledge
      regarding N. meningitidis capsule switching and vaccine pressure from capsular
      polysaccharide-based N. meningitidis vaccines, including conjugates. Main
      discussion topics were the host-bacteria relationship and N. meningitidis
      population, worldwide experience of meningococcal vaccination, and using existing
      experience to shape the future of meningococcal vaccination strategies. The
      workshop concluded that there is no current evidence to suggest that serogroup C
      conjugate vaccine pressure has resulted in meningococcal serogroup switching or
      replacement.

PMID- 17449150
TI  - Haemophilus influenzae meningitis 5 years after introduction of the Haemophilus
      influenzae type b conjugate vaccine in Brazil.
AB  - The long-term impact of Haemophilus influenzae type b (Hib) conjugate vaccine,
      introduced throughout Latin America in the late 1990s, has not been evaluated.
      Active surveillance for H. influenzae meningitis was performed from August 9,
      1996 to August 8, 2004 in Metropolitan Salvador, Brazil. Five years after the
      introduction of Hib conjugate vaccine, Hib meningitis incidence decreased from
      2.39 to 0.06 cases per 100,000 population (98%) overall, and from 60.9 to 3.1
      cases per 100,000 population (95%) in children <1 year of age. A transient
      serotype replacement phenomenon was observed associated with a small increase of
      meningitis due to two H. influenzae type a clonal groups. These findings indicate
      that Hib immunization campaign has led to the virtual elimination of Hib disease
      in this region.

PMID- 17449151
TI  - Protective immunity conferred by recombinant Pasteurella multocida lipoprotein E
      (PlpE).
AB  - The genes encoding Pasteurella multocida lipoprotein E (PlpE) and lipoprotein B
      (PlpB) were cloned from P. multocida strain X-73 (serotype A:1) and expressed in
      Escherichia coli. The protective immunity conferred by recombinant PlpE (r-PlpE)
      and PlpB (r-PlpB) on mice and chickens was evaluated. The results showed that
      mice immunized with 10microg of purified r-PlpE were protected (80-100% survival
      rate) against challenge infection with 10 or 20 LD(50) of P. multocida strains X
      73 (serotype A:1), P-1059 (serotype A:3) and P-1662 (serotype A:4). In contrast,
      mice immunized with r-PlpB were not protected. Chickens immunized with 100microg
      of purified r-PlpE were protected (63-100% survival rate) against lethal
      challenge infection with strains X-73 and P-1662, whereas those immunized with r
      PlpB were not. Sequence analyses showed that PlpE from different strains of P.
      multocida exhibited 90.8-100% sequence identity to each other, suggesting that
      PlpE might serve as a cross-protective antigen. This is the first report of a
      recombinant P. multocida antigen that confers cross protection on animals.

PMID- 17449152
TI  - 137Cs in the Danish Wadden Sea: contrast between tidal flats and salt marshes.
AB  - The 137Cs activity of salt marsh and tidal flat sediments of the northern part of
      the European Wadden Sea was studied based on a comprehensive dataset of 210Pb
      dated cores. The 137Cs inventory of salt marsh sediments shows a major peak
      corresponding to the Chernobyl accident in 1986, and a minor peak located in the
      late 1960s interpreted as the combined effect of atmospheric testing of nuclear
      weapons. Emissions from the nuclear reprocessing plant Sellafield are not
      reflected as peaks in 137Cs activity, but may contribute to the rising 137Cs
      activity in the years prior to 1986. The 137Cs activity of tidal flat sediments
      differs from salt marsh sediment in two respects. First, the activity is much
      lower and, second, the major peak in the 1980s is located in the beginning
      instead of in the middle of the decade. The differences in 137Cs inventory
      between the two environments are interpreted to result from repeated cycles of
      deposition/resuspension and mixing on tidal flats. A simple model illustrating
      the consequence of mixings returns an apparent shift of major peaks in 137Cs
      activities backwards in time corresponding to the mixing depth divided by the
      deposition rate.

PMID- 17449153
TI  - Dynamic biomechanical analysis of different olecranon fracture fixation devices-
      tension band wiring versus two intramedullary nail systems: an in-vitro cadaveric
      study.
AB  - BACKGROUND: The aim of this study was to develop a test-setup with continuous
      angle alteration to imitate joint motion for the evaluation of 3 different
      olecranon fracture fixation devices. METHODS: Twenty-one fresh cadaver upper
      extremities underwent olecranon fracture by the means of transverse osteotomy and
      received 3 different fixation systems. Group 1: Tension band wiring according to
      Weber. Group 2: XS-nail with 9 holes, all locked with 2mm threaded K-wires. Group
      3: Olecranon Nailing System with 90 mm length, locked with 2.7 mm screws, a
      variable angle locking hole for the proximal fragment and a proximal locking end
      cap. The servo-pneumatical test stand worked with a rotational angle-adjusted and
      a linear force-adjusted engine. The fracture model was dynamically tested under
      cyclic loading imitating elbow motion. There was a continuous angle alteration
      between 0 degrees and 100 degrees of flexion with continuous changing pull force
      between 25 N and 150 N. Two steel pins were placed in the proximal, two in the
      distal olecranon fragment for video analysis of the motion between the two pairs
      of pins. Displacement in the fracture gap was determined after 4 and 300 cycles.
      FINDINGS: After 300 cycles the displacement in the fracture fixation model was
      significantly higher in the tension-band-wiring-group than in the XS-nail group
      and the olecranon-nailing-system-group. INTERPRETATION: Other studies evaluating
      biomechanical properties of olecranon-osteosynthesis with joint-involvement did
      not change the force-direction dynamically. We introduce a test-setup with
      continuous angle alteration to imitate joint motion. This is an important step
      for accurate biomechanical evaluation of the treatment of different fixation
      methods in olecranon fractures. The tested nailing systems showed a higher
      stability in comparison to tension band wiring.

PMID- 17449154
TI  - Examining the association between parenting and childhood depression: a meta
      analysis.
AB  - Theoretical models posit that parenting plays a causal role in the development
      and maintenance of child psychological problems, yet meta-analytic findings
      indicate that parenting accounts for less than 6% of the variance in child
      externalizing problems and less than 4% of the variance in childhood anxiety.
      Extending the analysis to childhood depression, we conducted a meta-analysis of
      45 studies testing the association between parenting and childhood depression. We
      found that parenting accounted for 8% of the variance in child depression.
      Parental rejection was more strongly related to childhood depression than was
      parental control. Moreover, various subdimensions of parenting were
      differentially associated with childhood depression, with parental hostility
      toward the child most strongly related to child depression. Analyses also
      revealed that methodological factors (i.e., how parenting and child depression
      was conceptualized and assessed) moderated the parenting-childhood depression
      association. Inconsistent findings within the literature are partially
      attributable to variations from study to study in measurement quality. Closer
      attention to the precise measurement of these two constructs in future studies
      may lead to a more accurate estimate of the association between parenting and
      child depression. In all, the modest association between parenting and childhood
      depression indicates that factors other than parenting may account for the
      preponderance of variance in childhood depression.

PMID- 17449155
TI  - Do NHS clinicians and members of the public share the same views about reducing
      inequalities in health?
AB  - Decisions about how to allocate resources in health care are as much about social
      value judgements as they are about getting the medical facts right. In this
      context, it is important to compare the social preferences of members of the
      general public with those of National Health Service (NHS) staff involved in
      service delivery. A questionnaire eliciting peoples' preferences over maximising
      life expectancy and reducing inequalities in life expectancy between the highest
      and lowest social classes was completed by 271 members of the UK public and 220
      NHS clinicians. The two samples have different preferences with the general
      public showing a greater willingness than clinicians to sacrifice total health
      for a more equal distribution of health. These differences may highlight tensions
      between what the public wants and what clinicians want, and should be subject to
      further investigation.

PMID- 17449156
TI  - Towards an understanding of British public attitudes concerning human cloning.
AB  - The ability of scientists to apply cloning technology to humans has provoked
      public discussion and media coverage. The present paper reports on a series of
      studies examining public attitudes to human cloning in the UK, bringing together
      a range of quantitative and qualitative methods to address this question. These
      included a nationally representative survey, an experimental vignette study,
      focus groups and analyses of media coverage. Overall the research presents a
      complex picture of attitude to and constructions of human cloning. In all of the
      analyses, therapeutic cloning was viewed more favourably than reproductive
      cloning. However, while participants in the focus groups were generally negative
      about both forms of cloning, and this was also reflected in the media analyses,
      quantitative results showed more positive responses. In the quantitative
      research, therapeutic cloning was generally accepted when the benefits of such
      procedures were clear, and although reproductive cloning was less accepted there
      was still substantial support. Participants in the focus groups only
      differentiated between therapeutic and reproductive cloning after the issue of
      therapeutic cloning was explicitly raised; initially they saw cloning as being
      reproductive cloning and saw no real benefits. Attitudes were shown to be
      associated with underlying values associated with scientific progress rather than
      with age, gender or education, and although there were a few differences in the
      quantitative data based on religious affiliation, these tended to be small
      effects. Likewise in the focus groups there was little direct appeal to religion,
      but the main themes were 'interfering with nature' and the 'status of the
      embryo', with the latter being used more effectively to try to close down further
      discussion. In general there was a close correspondence between the media
      analysis and focus group responses, possibly demonstrating the importance of
      media as a resource, or that the media reflect public discourse accurately.
      However, focus group responses did not simply reflect media coverage.

PMID- 17449157
TI  - Profiles of depressive symptoms among African Americans and Caribbean Blacks.
AB  - Latent profile analysis was used to summarize profiles of depressive symptoms
      among a nationally representative sample of US-born and Caribbean-born Blacks.
      Analyses are based on the responses of 4915 African Americans and Caribbean
      Blacks from the National Survey of American Life. A high symptoms and a low
      symptoms class were identified. Age, gender, negative interaction within the
      individual's social network (e.g., conflict, demands, criticism) and racial
      discrimination were associated with depressive symptoms in the low symptoms
      class, whereas socioeconomic status, gender, emotional support and negative
      interaction were associated with depressive symptoms in the high symptoms class.
      The findings demonstrate the heterogeneity within the Black population in the USA
      and the distinct sociodemographic, family network and stress correlates of
      depressive symptoms for each latent class.

PMID- 17449158
TI  - Hyperinsulinaemia associated with beta-adrenoceptor antagonist in medicated
      bipolar patients during manic episode.
AB  - Hyperinsulinaemia, a pre-clinical condition which is considered to predict
      insulin resistance and metabolic syndrome, has not been sufficiently investigated
      in bipolar disorder, despite evidence to suggest that bipolar patients are at
      risk of developing insulin resistance. This study was set out to determine the
      alteration in fasting insulin levels and evaluate the factors associated with
      hyperinsulinaemia during manic episodes. Measurements were taken of the fasting
      plasma insulin and leptin levels, as well as the body mass index (BMI), amongst
      42 physically healthy bipolar I manic (DSM-IV) patients aged < or =45 with Young
      Mania Rating Scale (YMRS) scores of > or =26. These were then compared with their
      values in subsequent remission (YMRS < or =12). A total of 14 patients (33.3%) in
      acute mania and 30 patients (71.4%) in subsequent remission met the Taiwanese
      criteria for hyperinsulinaemia of > or =8.7 microIU/ml for men, and > or =11.3
      microIU/ml for women. Multiple analyses were then undertaken, without correction,
      as the exploratory analyses. The measurement, by logistic regression, of the use
      of propranolol in remission (odds ratio [OR]=10.04, 95% confidence interval [95%
      CI]=1.03-97.96) and the increase in BMI (OR=1.35, 95% CI=1.01-1.80) were found to
      have independent associations with hyperinsulinaemia in subsequent remission. Our
      results suggest that medicated bipolar manic patients are vulnerable to
      hyperinsulinaemia in early remission, particularly those gaining bodyweight or
      those using beta-adrenoceptor antagonist (beta-blockers), irrespective of the
      types of mood stabilizers or antipsychotics used.

PMID- 17449159
TI  - Atypical antipsychotics as "mood stabilizers": a retrospective chart review.
AB  - BACKGROUND: Introduction and common usage of atypical antipsychotics in
      maintenance therapy for bipolar disorders is an innovative perspective. The aim
      of the present study was to compare the efficacy of atypical antipsychotics (AA)
      used either as monotherapy or in combination with a mood stabilizer (MS) in the
      maintenance treatment. METHOD: 55 patients treated with AA either alone or in
      combination with a MS for bipolar I disorder which were followed up for 6 months
      were retrospectively evaluated. Clinical status was evaluated with Bech Rafaelsen
      Mania Rating Scale (BRMRS), 24-item Hamilton Depression Scale (HAMD) and Clinical
      Global Impressions Scale (CGI). RESULTS: Having similar demographic and clinical
      backgrounds, patients on with both treatment groups had significant clinical
      improvement. During the maintenance phase, numbers of total attacks were not
      significantly different between the two treatment groups. CONCLUSION: Our
      naturalistic, controlled retrospective observations suggest the potential use of
      atypical antipsychotics in the long-term management of bipolar I disorder. Larger
      and prospective studies are needed to determine the role of atypical
      antipsychotics more clearly in the maintenance treatment of bipolar disorder. To
      the best of our knowledge this is the first study comparing MS+AA with only AA
      treatment regimen.

PMID- 17449160
TI  - Personality traits associated with caffeine intake and smoking.
AB  - OBJECTIVES: Some studies find a relationship between certain personality traits,
      as impulsivity or sensation seeking, and caffeine consumption, but these studies
      do not consider the potential confounding effect of smoking on caffeine intake, a
      co-occurrence that has been well demonstrated in epidemiological and clinical
      studies. The main objective of this cross-sectional study was to analyze the
      association of personality with caffeine intake controlling for the effects of
      smoking; a secondary objective was to explore the effect of caffeine intake on
      the previously known relationship between personality and smoking. METHODS: A
      sample of 498 adults answered a self-questionnaire including socio-demographic
      variables, and items regarding consumption of tobacco and caffeine. Personality
      was measured by the Temperament and Character Inventory (TCI-125). We analyzed
      the association of personality traits with both caffeine intake and smoking,
      controlling the possible confounding effects of sex, age and each substance with
      the other one. RESULTS: Logistic regression analyses showed that the
      temperamental dimension of novelty seeking was associated with heavy caffeine
      consumption (>200 mg/day) (adjusted OR=2.0; 95% CI: 1.1-3.9), controlling for the
      effect of smoking. Moreover, novelty seeking was associated with both smoking
      (adjusted OR=1.8; 95% CI: 1.1-2.9) and heavy smoking (>20 cigarettes/day)
      (adjusted OR=1.8; 95% CI: 1.0-3.7), after controlling for the effect of caffeine
      intake. CONCLUSION: Our study offers an epidemiological evidence of the
      relationship of novelty seeking, considered to be associated with low basal
      dopaminergic activity, with both nicotine consumption and heavy caffeine intake,
      two substances that enhance dopaminergic neurotransmission.

PMID- 17449161
TI  - A pharmacodynamic study on clenbuterol-induced toxicity: beta1- and beta2
      adrenoceptors involvement in guinea-pig tachycardia in an in vitro model.
AB  - Beta(2)-receptor adrenergic agonists as clenbuterol and analogues are illegally
      used as growth promoters in cattle, in Europe, as well as in other countries.
      Following consumption of meat or liver, intoxication cases were described, and
      cardiovascular toxic effects (tachycardia, hypertension) were of clinical
      relevance. Therefore, we investigated whether heart rate increase induced by
      clenbuterol could depend upon stimulation of beta(1)- and/or beta(2)-adrenergic
      receptors, and in which ratio. We used in vitro guinea-pig atria, a model in
      which beta(1)-/beta(2)-receptors ratio is similar to that found in men. In our
      experiments both beta(1)- and beta(2)-receptors contributed to clenbuterol
      induced heart rate increase, but with a different potency. The selective beta(2)
      antagonist ICI-118,551 competitively antagonized responses to clenbuterol with
      high affinity (pA(2) 9.47+/-0.28, SchildSlope 0.98+/-0.20 not significantly
      different from unity, K(B) 0.34 nM). The selective beta(1)-antagonist atenolol
      antagonized clenbuterol with a relatively lower affinity (pA(2)=7.59+/-0.14), the
      SchildSlope=1.97+/-0.33 was significantly different from unity (P<0.05). Results
      show that clenbuterol stimulates guinea-pig heart rate by acting chiefly on
      beta(2)-adrenoceptor, although responses to clenbuterol apparently are mediated
      by an inter-play between both beta-adrenoceptors. Further experiments are
      necessary to understand which beta-adrenergic antagonists are of effectiveness to
      counteract cardiovascular effects in case of intoxication following clenbuterol,
      or other beta-adrenergic stimulants.

PMID- 17449162
TI  - The cytotoxicity induced by brucine from the seed of Strychnos nux-vomica
      proceeds via apoptosis and is mediated by cyclooxygenase 2 and caspase 3 in SMMC
      7221 cells.
AB  - To study the cytotoxicity of four alkaloids: brucine, strychnine, brucine N-oxide
      and isostrychnine from nux vomica on SMMC 7721 cells and their possible
      mechanisms, MET assay was used to examine the growth inhibitory effects of these
      alkaloids. Brucine revealed the strongest growth inhibitory effect on SMMC-7721
      cells. Furthermore, as directly observed under an inverted microscope,
      fluorescent microscope and transmission electronic microscope, brucine caused
      SMMC-7721 cell shrinkage, membrane blobbing, formation of apoptotic body as well
      as nucleus condensation, all of which are typical characteristics of apoptotic
      programmed cell death. In addition, brucine dose-dependently caused SMMC-7721
      cells apoptosis via formation of subdipolid DNA and phosphatidylserine
      externalization, as evidenced by flow cytometry analysis. The brucine-induced
      apoptosis was partially attributed to the activation of caspase 3 as well as
      cyclooxygenase 2 inhibition, since neither caspase 3 specific inhibitor, z-DEVD
      fmk nor was exogenous addition of prostaglandin E(2) able to completely abrogate
      the brucine-induced SMMC 7721 cell apoptosis. In sum, this paper indicate that
      the major alkaloids present in the seed of Strychnos nux-vomica are effective
      against SMMC-7721 cells proliferation, among which brucine proceeds SMMC-7721
      cells death via apoptosis, probably through the participation of caspase 3 and
      cyclooxygenase 2.

PMID- 17449163
TI  - Studying gene expression profile of rat neuron exposed to 1800MHz radiofrequency
      electromagnetic fields with cDNA microassay.
AB  - A widespread use of mobile phone (MP) evokes a growing concern for their possible
      adverse effects on human, especially the brain. Gene expression is a unique way
      of characterizing how cells and organism adapt to changes in the external
      environment, so the aim of this investigation was to determine whether 1800 MHz
      radiofrequency electromagnetic fields (RF EMF) can influence the gene expression
      of neuron. Affymetrix Rat Neurobiology U34 array was applied to investigate the
      changes of gene expression in rat neuron after exposed to the pulsed RF EMF at a
      frequency of 1800 MHz modulated by 217 Hz which is commonly used in MP. Among
      1200 candidate genes, 24 up-regulated genes and 10 down-regulated genes were
      identified after 24-h intermittent exposure at an average special absorption rate
      (SAR) of 2 W/kg, which are associated with multiple cellular functions
      (cytoskeleton, signal transduction pathway, metabolism, etc.) after functional
      classification. The results were further confirmed by quantitative real-time
      polymerase chain reaction (RT PCR). The present results indicated that the gene
      expression of rat neuron could be altered by exposure to RF EMF under our
      experimental conditions.

PMID- 17449164
TI  - Ruptured left subclavian artery aneurysm presenting as upper airway obstruction
      in von Recklinghausen's disease.
AB  - Aneurysms arising from the subclavian artery are very rare vascular abnormalities
      in von Recklinghausen's disease, which often have a silent clinical presentation
      and are difficult to diagnose before rupture. We report a case of von
      Recklinghausen's disease with life-threatening upper airway obstruction caused by
      spontaneous rupture of the left subclavian artery aneurysm in a 46-year-old
      woman. The diagnosis was eventually confirmed by a reconstructed enhanced
      computed tomography of aorta. We emphasise the importance of it as a differential
      diagnosis because life-threatening upper airway obstruction may develop in such
      patient.

PMID- 17449165
TI  - Evaluation of a tape removal test to assess neurological deficit after cardiac
      arrest in rats.
AB  - BACKGROUND: In animal models of cardiocirculatory arrest (CA) it is of major
      interest to establish tests that can assess neurological damage after global
      cerebral ischaemia following CA. We evaluated a tape removal test with regard to
      detection of sensorimotor deficit, comparing it to the Neurological Deficit Score
      (NDS) in an established model of global cerebral ischaemia after CA in rats.
      METHODS: Rats were subjected to either 6 min of CA followed by cardiopulmonary
      resuscitation (CPR) or a sham operation. At 1, 3 and 7 days from the
      intervention, two different neurological tests were applied to all animals: in
      the tape removal test, the time was measured from attachment of adhesive tapes to
      the front paws until the animals removed them using their teeth and compared to
      latencies in the sham group. The NDS assessed two parameters ("travel beam" and
      "stop at the edge of a table"). Receiver operating characteristic (ROC) analysis
      was used to compare tests. RESULTS: In the tape removal test, all animals of the
      CPR group showed a clear neurological deficit throughout the observation period
      with a marked recovery until day 7 (pre-CA: 4s, 1 day: 180 s, 3 days: 165 s, 7
      days: 44 s; data are median values). Latencies differed significantly from those
      of sham-operated animals (1 day: P<0.001, 3 days: P=0.003, 7 days: P=0.006). ROC
      analysis showed that the tape removal test but not the NDS was appropriate for
      detecting neurological damage 3 and 7 days after restoration of spontaneous
      circulation (ROSC). Histological examination confirmed neuronal damage to the
      hippocampus, cortex, thalamus and striatum. CONCLUSION: In the present study, a
      clinically relevant sensorimotor deficit after global cerebral ischaemia
      following cardiac arrest in rats has been quantified for the first time by using
      a tape removal test. The tape removal test is a sensitive method that can be
      easily applied to test large numbers of animals in future studies.

PMID- 17449166
TI  - Investigating radial glia in vitro.
AB  - During mammalian neurogenesis newly born neurons migrate radially along the
      extended bipolar process of cells termed radial glia. Our views of radial glia as
      a 'static' support/guide cell have changed over recent years. It is now clear
      that within the developing cortex, and possibly the entire central nervous system
      (CNS), radial glia actively divide, producing daughter cells that include both
      neurons and glia. A subset of forebrain radial glia may serve as the founders of
      adult forebrain neural stem cells and genetic disruption of normal radial glia
      function can result in tumorigenesis or congenital neurological disorders.
      Elucidating the cell intrinsic and environmental cues that regulate radial glia
      behaviour is therefore essential for a full understanding of mammalian CNS
      development and physiology. Here, we review those studies in which radial glia
      have been investigated in vitro following isolation from foetal tissues or
      differentiation of embryonic stem (ES) cells. We discuss how these approaches,
      together with an ability to expand radial glia-like neural stem (NS) cell lines,
      may offer unique opportunities in basic and applied neurobiology.

PMID- 17449167
TI  - Regional brain activity and strenuous exercise: predicting affective responses
      using EEG asymmetry.
AB  - Previous research using the model proposed by Davidson has shown that resting
      frontal electroencephalographic (EEG) asymmetry can predict affective responses
      to aerobic exercise at moderate intensities. Specifically, greater relative left
      frontal activity has been shown to predict positive affect (i.e., energy)
      following exercise. The purpose of this study was to determine if resting frontal
      EEG asymmetry would predict affective responses following strenuous exercise.
      Thirty participants (13 women, 17 men) completed a maximal graded exercise test
      on a treadmill. EEG was recorded prior to exercise. Affect was measured by the
      Activation Deactivation Adjective Check List prior to the graded exercise test,
      immediately following, 10 and 20-min following exercise. Greater relative left
      frontal activity predicted tiredness and calmness during recovery from exercise,
      but not tension or energy. Tiredness and calmness following exercise covaried,
      suggesting that tiredness following exercise might not have been linked with
      displeasure. These findings offer further support for the link between EEG
      asymmetry and affective responses to exercise.

PMID- 17449168
TI  - A holistic framework for design of cost-effective minimum water utilization
      network.
AB  - Water pinch analysis (WPA) is a well-established tool for the design of a maximum
      water recovery (MWR) network. MWR, which is primarily concerned with water
      recovery and regeneration, only partly addresses water minimization problem.
      Strictly speaking, WPA can only lead to maximum water recovery targets as opposed
      to the minimum water targets as widely claimed by researchers over the years. The
      minimum water targets can be achieved when all water minimization options
      including elimination, reduction, reuse/recycling, outsourcing and regeneration
      have been holistically applied. Even though WPA has been well established for
      synthesis of MWR network, research towards holistic water minimization has lagged
      behind. This paper describes a new holistic framework for designing a cost
      effective minimum water network (CEMWN) for industry and urban systems. The
      framework consists of five key steps, i.e. (1) Specify the limiting water data,
      (2) Determine MWR targets, (3) Screen process changes using water management
      hierarchy (WMH), (4) Apply Systematic Hierarchical Approach for Resilient Process
      Screening (SHARPS) strategy, and (5) Design water network. Three key
      contributions have emerged from this work. First is a hierarchical approach for
      systematic screening of process changes guided by the WMH. Second is a set of
      four new heuristics for implementing process changes that considers the
      interactions among process changes options as well as among equipment and the
      implications of applying each process change on utility targets. Third is the
      SHARPS cost-screening technique to customize process changes and ultimately
      generate a minimum water utilization network that is cost-effective and
      affordable. The CEMWN holistic framework has been successfully implemented on
      semiconductor and mosque case studies and yielded results within the designer
      payback period criterion.

PMID- 17449169
TI  - Number of daytime micturitions and volume voided per micturition in the
      evaluation of efficacy of drugs for overactive bladder: findings from randomized
      clinical trials.
AB  - OBJECTIVE: To analyze the relationship between mean volume voided per micturition
      and number of daytime micturitions. METHODS: We reviewed data from randomized
      clinical trials on the medical treatment of overactive bladder published in the
      international literature between 1997 and 2004. Fourteen studies including data
      on these two parameters were identified. RESULTS: Six studies compared
      tolterodine with placebo, two tolterodine and oxybutynin with placebo, two
      tolterodine with oxybutynin, two solifenacin and tolterodine with placebo, one
      oxybutynin CR with oxybutynin IR, and one different doses of solifenacin. The
      correlation between the percent change in the mean voided volume and in the
      number of daytime micturitions was assessed using the Spearman rank correlation
      coefficient (r), with r=-0.67 for all the studies. For groups of patients treated
      with each drug, we found r=-0.09 for oxybutynin, r=-0.59 for tolterodine, r=-0.85
      for solifenacin, and r=-0.34 for placebo. CONCLUSION: The results of this
      analysis suggest that in the evaluation of the efficacy of a drug for overactive
      bladder, the mean volume voided per micturition may be a useful measure of
      efficacy.

PMID- 17449170
TI  - Eumycetoma presenting as a cerebellopontine angle mass lesion.
AB  - Eumycetoma in the cerebellopontine angle region is extremely uncommon with no
      case being reported as per an extensive review of the literature by the authors.
      The authors report a case of cerebellopontine angle eumycetoma in a young female
      managed by subtotal decompression and antifungal treatment. The pre-operative
      diagnosis of eumycetoma in this location is extremely difficult and the role of
      histopathology is very important to characterize this uncommon lesion. The
      prognosis of this bizarre pathology is dismal despite all treatment modalities as
      compared to the usual tumors of the cerebellopontine angle that generally have a
      favorable outcome.

PMID- 17449171
TI  - Early surgical treatment of middle cerebral artery aneurysms associated with
      intracerebral haematoma.
AB  - OBJECTIVE: Patients with haematoma secondary to middle cerebral artery aneurysm
      often require urgent surgical treatment consisting of evacuation of the haematoma
      and aneurysmal clipping. METHODS: . We present our experience over 5 years with
      12 patients who underwent surgery before the first 8h of bleeding. Surgery
      included craniotomy, evacuation of the haematoma, and aneurysmal clipping.
      Preoperative angiography was performed in all cases. RESULTS: All patients had a
      score of 4 or 5 on the scale of the World Federation of Neurological Surgeons.
      Five of the patients were evolving well after 1 year. Clinical status upon
      admission, temporal lobe versus sylvian location of the haematoma, right
      hemisphere involvement, and a midline deviation of less than 2 cm, were all most
      frequently associated with a good prognosis. CONCLUSIONS: In our experience, and
      in the literature available to us, early surgery in patients with haematoma
      secondary to middle cerebral artery aneurysm offers acceptable results in
      patients with World Federation of Neurological Surgeons scores of 4 or 5.

PMID- 17449172
TI  - Vitamin E succinate in combination with mda-7 results in enhanced human ovarian
      tumor cell killing through modulation of extrinsic and intrinsic apoptotic
      pathways.
AB  - Adenovirus-mediated mda-7 (Ad-mda7) gene transfer has been shown to induce
      apoptosis in various human cancer cells while sparing normal cells. Vitamin E
      succinate (VES) is also known to exhibit antitumor activity against a number of
      human cancer cell lines. We hypothesized that a combination of the two agents
      would produce an enhanced antitumor effect in MDAH2774 human ovarian cancer
      cells. Treatment of MDAH2774 cells with Ad-mda7 plus VES resulted in enhanced
      antitumor activity that involved the activation of two apoptotic pathways.
      Activation of the extrinsic pathway was demonstrated by increased cell-surface
      Fas expression and cleavage of Bid and caspase-8. Activation of the intrinsic
      pathway was demonstrated by disruption of mitochondrial potential; and activation
      of downstream capase-9 and caspase-3 via cytochrome C release. In contrast, the
      combination of Ad-mda7 plus VES did not show any antitumor activity against
      normal fibroblasts, indicating selective tumor cell killing. Our in vitro results
      provide a basis for further preclinical testing of Ad-mda7 plus VES as a
      potential cancer treatment strategy.

PMID- 17449173
TI  - Gene expression and promoter methylation of the XIAP-associated Factor 1 in renal
      cell carcinomas: correlations with pathology and outcome.
AB  - Transcriptional downregulation of the putative tumor suppressor gene XIAP
      associated Factor 1 (XAF1) by promoter methylation has been shown to relate to
      tumor progression of gastric and bladder cancer. This study determined the mRNA
      expression levels and the methylation status of XAF1 by real-time RT-PCR and
      quantitative methylation specific PCR in tumor tissue obtained from 91 renal cell
      carcinoma (RCC) patients (median follow-up 50.5 months) following surgical
      treatment. Expression data was correlated to histopathological variables and
      outcome. XAF1 expression levels were not related to standard pathological
      parameters for outcome prediction but results from crude and explorative
      multivariable-adjusted analyses revealed low XAF1 levels to significantly
      increase the relative risk (RR) for tumor recurrence (RR 4.6; CI 95%: 1.4-14.6)
      and tumor-related death (RR 3.6; CI 95%: 1.4-9.7). The association of low XAF1
      expression with an abbreviated recurrence-free (p=0.009) and disease-specific
      survival (p=0.005) was most pronounced in patients with locally advanced (pT3)
      tumors. XAF1 promoter methylation was rarely detected (10%) but, if present, XAF1
      mRNA expression levels correlated inversely to the normalized index of
      methylation (p=0.01). Our findings suggest that low XAF1 mRNA expression levels
      relate to an unfavorable clinical course in RCC patients. Promoter methylation
      may be one, but probably not the essential mechanism for transcriptional
      downregulation of the XAF1 gene in RCC.

PMID- 17449174
TI  - Origin and prognostic value of circulating KRAS mutations in lung cancer
      patients.
AB  - Because of the current controversy on the origin and clinical value of
      circulating KRAS codon 12 mutations in lung cancer, we screened 180 patients
      using a combined restriction fragment-length polymorphism and polymerase chain
      reaction (RFLP-PCR) assay. We detected KRAS mutations in 9% plasma samples and 0%
      matched lymphocytes. Plasma KRAS mutations correlated significantly with poor
      prognosis. We validated the positive results in a second laboratory by DNA
      sequencing and found matching codon 12 sequences in blood and tumor in 78%
      evaluable cases. These results support the notion that circulating KRAS mutations
      originate from tumors and are prognostically relevant in lung cancer.

PMID- 17449175
TI  - G-CSF enhances stem cell proliferation in rat hippocampus after transient middle
      cerebral artery occlusion.
AB  - Granulocyte colony-stimulating factor (G-CSF) enhances the survival and
      stimulates the proliferation of neutrophil progenitors. Recently, the
      neurogenerative effect of G-CSF has been intensely investigated. In this study,
      we explored the possibility that G-CSF enhanced the cell proliferation in the rat
      dentate gyrus (DG) after focal cerebral ischemia, using a rat transient middle
      cerebral artery occlusion (tMCAO) model. At 7 days after tMCAO, the number of 5
      bromodeoxyuridine (BrdU)-positive cells in the G-CSF-treated group was
      significantly increased compared with that in the vehicle-treated group in the
      ipsilateral SGZ (16.6+/-5.5/mm(2) in the vehicle-treated group versus 33.0+/
      7.2/mm(2) in the G-CSF-treated group, **p<0.01) and in the ipsilateral GCL
      (14.2+/-2.8/mm(2) in the vehicle-treated group versus 21.0+/-3.8/mm(2) in the G
      CSF-treated group, *p<0.05). This result showed the possibility of a
      neurogenerative role of G-CSF after tMCAO in rats.

PMID- 17449176
TI  - D-cycloserine reduces neuropathic pain behavior through limbic NMDA-mediated
      circuitry.
AB  - Human brain imaging studies suggest that chronic neuropathic pain has a strong
      emotional component that is mediated by medial prefrontal cortex (mPFC) activity;
      in rodents, the mPFC is involved in emotional and cognitive aspects of behavior,
      including the extinction of Pavlovian fear conditioning. Together, these findings
      suggest that the cortex may modulate the memory trace of pain. As D-cycloserine
      (DCS), a partial agonist of the NMDA receptor, can enhance learning and
      potentiate the extinction of acquired fear, in the present study we tested its
      efficacy in neuropathic pain behavior. In rats with spared nerve injury (SNI),
      repeated daily oral administration of DCS reduced mechanical sensitivity of the
      injured limb in a dose-dependent manner; this effect continued for weeks after
      the cessation of DCS treatment. In addition, re-exposure to DCS further enhanced
      antinociceptive behavior. Repeated oral DCS administration also reduced cancer
      chemotherapy drug-induced neuropathic pain behavior. Infusions of DCS directly
      into the mPFC (especially within prelimbic cortex) or the amygdala (but not into
      thalamus, insula, or occipital cortex) acutely induced antinociception in SNI
      rats. The antinociceptive effect of intra-mPFC DCS infusions was mimicked by NMDA
      and glycine, and blocked by HA 966. In the mPFC of SNI rats, NR2B expression was
      down-regulated; however, this effect was reversed with repeated oral DCS. Lastly,
      infusions of DCS into mPFC reversed place avoidance behavior induced by
      mechanical stimulation of the injured paw in SNI rats. These findings indicate
      that limbic NMDA-mediated circuitry is involved in long-term reduction in
      neuropathic pain behavior.

PMID- 17449177
TI  - Should we be reluctant to prescribe opioids for chronic non-malignant pain?

PMID- 17449178
TI  - Risk factors for clinically recognized opioid abuse and dependence among veterans
      using opioids for chronic non-cancer pain.
AB  - A central question in prescribing opioids for chronic non-cancer pain (CNCP) is
      how to best balance the risk of opioid abuse and dependence with the benefits of
      pain relief. To achieve this balance, clinicians need an understanding of the
      risk factors for opioid abuse, an issue that is only partially understood. We
      conducted a secondary data analysis of regional VA longitudinal administrative
      data (years 2000-2005) for chronic users of opioids for CNCP (n=15,160) to
      investigate risk factors for the development of clinically recognized (i.e.,
      diagnosed) opioid abuse or dependence among these individuals. We analyzed four
      broad groups of possible risk factors: (i) non-opioid substance abuse disorders,
      (ii) painful physical health disorders, (iii) mental health disorders, and (iv)
      socio-demographic factors. In adjusted models, a diagnosis of non-opioid
      substance abuse was the strongest predictor of opioid abuse/dependence (OR=2.34,
      p<0.001). Mental health disorders were moderately strong predictors (OR=1.46,
      p=0.005) of opioid abuse/dependence. However, the prevalence of mental health
      disorders was much higher than the prevalence of non-opioid substance abuse
      disorders (45.3% vs. 7.6%) among users of opioids for CNCP, suggesting that
      mental health disorders account for more of the population attributable risk for
      opioid abuse than does non-opioid substance abuse. Males, younger adults, and
      individuals with greater days supply of prescription opioids dispensed in 2002
      were more likely to develop opioid abuse/dependence. Clinicians need to carefully
      screen for substance abuse and mental health disorders in candidates for opioid
      therapy and facilitate appropriate treatment of these disorders.

PMID- 17449179
TI  - Activation of the cortical pain network by soft tactile stimulation after
      injection of sumatriptan.
AB  - The anti-migraine drug sumatriptan often induces unpleasant somatosensory side
      effects, including a dislike of being touched. With a double-blind cross-over
      design, we studied the effects of sumatriptan and saline on perception (visual
      analogue scale) and cortical processing (functional magnetic resonance imaging)
      of tactile stimulation in healthy subjects. Soft brush stroking on the calf (n=6)
      was less pleasant (p<0.04) and evoked less activation of posterior insular cortex
      in the sumatriptan compared to the saline condition. Soft brushing activated pain
      processing regions (anterior insular, lateral orbitofrontal, and anterior
      cingulate cortices, and medial thalamus) only in the sumatriptan condition,
      whereas activation of somatosensory cortices was similar in both conditions. Soft
      brush stroking on the palm (n=6) was equally pleasant in both conditions. One
      possible mechanism for the activation of pain processing regions by brush
      stroking is sensitization of nociceptors by sumatriptan. Another possibility is
      inhibition of a recently discovered system of low-threshold unmyelinated tactile
      (CT) afferents that are present in hairy skin only, project to posterior insular
      cortex, and serve affective aspects of tactile sensation. An inhibition of
      impulse transmission in the CT system by sumatriptan could disinhibit nociceptive
      signalling and make light touch less pleasant. This latter alternative is
      consistent with the observed reduction in posterior insular cortex activation and
      the selective effects of stimulation on hairy compared to glabrous skin, which
      are not explained by the nociceptor sensitization account.

PMID- 17449180
TI  - The context of a noxious stimulus affects the pain it evokes.
AB  - The influence of contextual factors on the pain evoked by a noxious stimulus is
      not well defined. In this study, a -20 degrees C rod was placed on one hand for
      500 ms while we manipulated the evaluative context (or 'meaning') of, warning
      about, and visual attention to, the stimulus. For meaning, a red (hot, more
      tissue damaging) or blue (cold, less tissue damaging) visual cue was used. For
      warning, the stimulus occurred after the cue or they occurred together. For
      visual attention, subjects looked towards the stimulus or away from it. Repeated
      measures ANCOVA was significant (alpha=0.0125). Stimuli associated with a red cue
      were rated as hot, with the blue cue as cold (difference on an 11 point scale
      approximately 5.5). The red cue also meant the pain was rated as more unpleasant
      (difference approximately 3.5) and more intense (difference approximately 3). For
      stimuli associated with the red cue only, the pain was more unpleasant when the
      stimulus occurred after the cue than when it didn't (difference approximately
      1.1). Pain was rated as more intense, and the stimulus as hotter, when subjects
      looked at the red-cued stimulus than when they didn't (difference approximately
      0.9 for pain intensity and approximately 2 for temperature). We conclude that
      meaning affects the experience a noxious stimulus evokes, and that warning and
      visual attention moderate the effects of meaning when the meaning is associated
      with tissue-damage. Different dimensions of the stimulus' context can have
      differential effects on sensory-discriminative and affective-emotional components
      of pain.

PMID- 17449181
TI  - Analgesic properties of oleoylethanolamide (OEA) in visceral and inflammatory
      pain.
AB  - Oleoylethanolamide (OEA) is a natural fatty acid amide that mainly modulates
      feeding and energy homeostasis by binding to peroxisome proliferator-activated
      receptor-alpha (PPAR-alpha) [Rodriguez de Fonseca F, Navarro M, Gomez R, Escuredo
      L, Navas F, Fu J, et al. An anorexic lipid mediator regulated by feeding. Nature
      2001;414:209-12; Fu J, Gaetani S, Oveisi F, Lo Verme J, Serrano A, Rodriguez de
      Fonseca F, et al. Oleoylethanolamide regulates feeding and body weight through
      activation of the nuclear receptor PPAR-alpha. Nature 2003;425:90-3].
      Additionally, it has been proposed that OEA could act via other receptors,
      including the vanilloid receptor (TRPV1) [Wang X, Miyares RL, Ahern GP.
      Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and
      reduces short-term food intake in mice via capsaicin receptor TRPV1. J Physiol
      2005;564:541-7.] or the GPR119 receptor [Overton HA, Babbs AJ, Doel SM, Fyfe MC,
      Gardner LS, Griffin G, et al. Deorphanization of a G protein-coupled receptor for
      oleoylethanolamide and its use in the discovery of small-molecule hypophagic
      agents. Cell Metab 2006;3:167-175], suggesting that OEA might subserve other
      physiological roles, including pain perception. We have evaluated the effect of
      OEA in two types of nociceptive responses evoked by visceral and inflammatory
      pain in rodents. Our results suggest that OEA has analgesic properties reducing
      the nociceptive responses produced by administration of acetic acid and formalin
      in two experimental animal models. Additional research was performed to
      investigate the mechanisms underlying this analgesic effect. To this end, we
      evaluated the actions of OEA in mice null for the PPAR-alpha receptor gene and
      compared its actions with those of PPAR-alpha receptor wild-type animal. We also
      compared the effect of MK-801 in order to evaluate the role of NMDA receptor in
      this analgesia. Our data showed that OEA reduced visceral and inflammatory
      responses through a PPAR-alpha-activation independent mechanism. Co
      administration of subanalgesic doses of MK-801 and OEA produced an analgesic
      effect, suggesting the participation of glutamatergic transmission in the
      antinociceptive effect of OEA. This study represents a novel approach to the
      examination of the effectiveness of OEA in nociceptive responses and provides a
      framework for understanding its biological functions and endogenous targets in
      visceral and inflammatory pain.

PMID- 17449183
TI  - Three-dimensional atom probe characterization of alloy element partitioning in
      cementite during tempering of alloy steel.
AB  - Hardness measurements confirm that the martensitic microstructure of an alloy
      steel, AISI/SAE 4340, is significantly more resistant to softening, compared to
      the martensitic microstructure of a high-purity Fe-0.4% C alloy, at tempering
      temperatures, 300-400 degrees C, just above the temperatures where cementite
      replaces transition carbides in the martensitic matrix. Three-dimensional atom
      probe (3DAP) analyses of the 4340 steel show that Si rejection from the cementite
      is first detected after low-temperature tempering for times of 1 h. After 10-h
      tempering at 400 degrees C, Mn and Cr contents are increased, and Ni contents
      decreased, in cementite according to their carbide- and non-carbide-forming
      tendencies, respectively. The results are discussed with respect to the
      diffusivity of the substitutional alloying elements in the 4340 steel, and the
      effect that such diffusion-controlled redistribution would have on maintaining
      fine distributions of cementite that resist softening during tempering.

PMID- 17449182
TI  - Pain, problem drug use history, and aberrant analgesic use behaviors in persons
      living with HIV.
AB  - Little is known about the relationship between pain and aberrant use of
      prescription analgesics in persons living with HIV. We examined the predictive
      and concurrent associations among pain, aberrant use of opioids, and problem drug
      use history in a nationally representative longitudinal sample of 2267 HIV+
      persons. Covariance structure analyses tested a conceptual model wherein HIV+
      patients with a history of problematic drug use (n=870), compared to those
      without such history (n=1397), were hypothesized to report more pain and aberrant
      opioid use, as well as use of opioids specifically for pain at baseline and 6-
      and 12-month follow-ups, after controlling for key sociodemographic
      characteristics. In support of the hypothesized model, patients with a history of
      problematic drug use reported more pain, and were more likely to report aberrant
      use of prescription analgesics, as well as use of such medications specifically
      for pain, compared to patients without such history. We also found a trend toward
      greater stability of aberrant opioid use over time in problem drug users compared
      with non-problem users suggesting a persistent pattern of inappropriate
      medication use in the former group. Our findings suggest that even though HIV+
      persons with a history of problematic drug use report on-going patterns of using
      prescription analgesics specifically for pain, these patients continued to
      experience persistently higher levels of pain, relative to non-problem users.
      Among non-problem users, pain was not linked to aberrant use of opioids, but was
      linked to the use of such medications specifically for pain.

PMID- 17449184
TI  - Infectivity of seropositive dogs, showing different clinical forms of
      leishmaniasis, to Lutzomyia longipalpis phlebotomine sand flies.
AB  - Visceral leishmaniasis (VL) is a growing zoonosis with an increasing number of
      new cases and a rapid geographical spreading of the disease. In the present
      study, a canine survey was carried out in the city of Montes Claros (320,000
      inhabitants), an endemic area of American visceral leishmaniasis in the state of
      Minas Gerais, Brazil. A total number of 4795 dogs were examined by serology,
      which showed a rate of seropositivity of 5%. Isoenzymatic analysis confirmed
      Leishmania infantum chagasi as the local aetiological agent of CVL. Canine
      tissues were assayed for the presence of Leishmania parasite DNA using different
      techniques. The infectivity of asymptomatic, oligosymptomatic and symptomatic
      seropositive dogs was tested by xenodiagnosis using laboratory reared Lutzomyia
      longipalpis. Rates of infection of 5.4%, 5.1% and 28.4% were found for the
      phlebotomine sand flies that fed in asymptomatic, oligosymptomatic and
      symptomatic dogs, respectively. Our results indicate that, under experimental
      conditions, symptomatic dogs are about four times more infective to VL vectors
      than oligosymptomatic or asymptomatic animals. The lower infectivity rates of
      dogs displaying any of the last two clinical forms of leishmaniasis, however,
      must be taken into account in the epidemiology of CVL.

PMID- 17449185
TI  - The role of different subregions of the basolateral amygdala in cue-induced
      reinstatement and extinction of food-seeking behavior.
AB  - Reinstatement of previously extinguished instrumental responding for drug-related
      cues has been used as an animal model for relapse of drug abuse, and is disrupted
      by inactivation of the basolateral amygdala (BLA). However, the role that the BLA
      plays in reinstatement induced by cues associated with natural rewards is
      unclear. The present study assessed the effects of inactivation of different
      regions of the BLA in cue-induced reinstatement of food-seeking behavior and in
      the extinction of instrumental responding for food. In experiment 1, rats
      acquired a lever pressing response for food reward paired with a light/tone
      conditioned stimulus (CS). They were then subjected to extinction training, where
      both food and the CS were withheld. Reinstatement of extinguished responding was
      measured during response-contingent presentations of the CS alone. Following
      saline infusions into the caudal or rostral BLA, rats displayed a significant
      increase in lever pressing during reinstatement sessions. Inactivation of these
      subregions with bupivacaine did not attenuate responding for the CS in the
      absence of food delivery. In fact, inactivation of the caudal BLA potentiated
      responding relative to vehicle treatments. Analysis of within-session responding
      revealed that caudal BLA inactivation retarded extinction of lever pressing in
      response to the CS. In experiment 2, inactivation of the caudal BLA on the first
      or second day of extinction training significantly retarded the acquisition of
      extinction learning on the following day. These data indicate that that the
      caudal BLA may play a specific role in the extinction of appetitive conditioned
      responses, by monitoring changes in the reinforcing value of pavlovian
      conditioned stimuli linked to action-outcome associations once these associations
      have been formed. Moreover, these findings support a growing body of evidence
      indicating that separate neural circuits incorporating the BLA may play different
      roles in mediating reinstatement of reward-seeking behaviors induced by either
      drug or food related stimuli.

PMID- 17449186
TI  - Inhibition of neurosteroid synthesis increases asphyxia-induced brain injury in
      the late gestation fetal sheep.
AB  - Allopregnanolone (AP) is a potent GABAergic agonist that suppresses CNS activity,
      seizure threshold, and excitotoxicity in the adult brain. AP is present in the
      fetal sheep brain and increases rapidly after asphyxial insult due to increased
      5alpha-reductase type-2 (5alphaR-2) expression. The aim of this study was to use
      finasteride to suppress fetal neurosteroid synthesis, and then determine the
      effect on brain injury, particularly in the hippocampus, of asphyxia induced in
      utero by brief occlusion of the umbilical cord. Catheters and an inflatable
      umbilical cord cuff were implanted in fetal sheep at approximately 125 days
      gestation. Five days later the fetuses received either finasteride (20 mg/kg/h)
      or vehicle (40% hydroxypropyl-beta-cyclodextrin) for 2 h. The umbilical cord was
      occluded (UCO) for 5 min at 30 min after starting the infusion. The fetal brain
      was obtained 24 h later for examination of activated caspase-3 expression as an
      index of apoptosis, and to measure AP content. Finasteride treatment alone
      significantly reduced AP content and increased the number of caspase-3 positive
      cells in the hippocampus, cerebellum, and the subcallosal bundle, indicating that
      AP modulates the normal rate of apoptosis in the developing brain. UCO in vehicle
      and finasteride-treated fetuses produced a similar, marked decrease in O2
      saturation (5.8+/-0.6%), but after finasteride treatment UCO caused a
      significantly greater increase in the number of caspase-3 positive cells in the
      hippocampal cornu ammonis 3 (CA3) (57.3+/-1.6%) compared with the vehicle-treated
      fetuses. Thus, 5alpha-reduced steroids such as AP may be protective in reducing
      cell death following acute fetal asphyxia. Perturbation of normal fetal
      neurosteroid levels in late gestation (e.g. due to preterm birth, or maternal
      synthetic steroid treatment to induce fetal lung maturation) could adversely
      affect brain development and increase its vulnerability to injury.

PMID- 17449188
TI  - Mesenchymal stem cells transfected with HCN2 genes by LentiV can be modified to
      be cardiac pacemaker cells.
AB  - Pacemaker cells differ from common cardiomyocytes for the presence of a
      spontaneous depolarization process during the diastolic phase of the cardiac
      cycle, which is due to the hyperpolarization-activated cyclic nucleotide-gated
      (HCN) channel genes, providing the presence of an inward current. With this in
      mind, we embarked on a study to test proof-of-principle if genetically engineered
      mesenchymal stem cells (MSCs) transfected with HCN2 genes can be modified to be
      cardiac pacemaker cells. In addition to expressing an anticipated high level of
      hHCN2 gene, MSCs transfected with HCN2 genes by LentiV in our study also
      expressed characteristic hHCN2 protein, the I(f)-like current and were capable of
      increasing the spontaneous beating rate of cocultured cardiac myocytes. Control
      MSCs did not exert these effects. Thus, the electrical effects of the MSCs
      transfected with the hHCN2 gene were similar to the effects of overexpression of
      the same gene in the myocytes in vitro system. For stable genetic modification,
      we used the self-inactivating HIV1-based lentiviral vector (LentiV) for transgene
      delivery in our study, which can integrate transgene into the host genome. This
      unique property makes LentiV ideal for modifying MSCs, which allows persistent
      transgene expression. With these findings, we hypothesize that genetically
      engineered MSCs transfected with HCN2 genes by LentiV can be modified to be
      cardiac pacemaker cells.

PMID- 17449187
TI  - Persistent neuroendocrine and behavioral effects of a novel, etiologically
      relevant mouse paradigm for chronic social stress during adolescence.
AB  - Chronic stress is widely regarded as a key risk factor for a variety of diseases.
      A large number of paradigms have been used to induce chronic stress in rodents.
      However, many of these paradigms do not consider the etiology of human stress
      associated disorders, where the stressors involved are mostly of social nature
      and the effects of the stress exposure persist even if the stressor is
      discontinued. In addition, many chronic stress paradigms are problematic with
      regard to stress adaptation, continuity, duration and applicability. Here we
      describe and validate a novel chronic social stress paradigm in male mice during
      adolescence. We demonstrate persistent effects of chronic social stress after 1
      week of rest, including altered adrenal sensitivity, decreased expression of
      corticosteroid receptors in the hippocampus and increased anxiety. In addition,
      pharmacological treatments with the antidepressant paroxetine (SSRI) or with the
      corticotropin-releasing hormone receptor 1 antagonist DMP696 were able to prevent
      aversive long-term consequences of chronic social stress. In conclusion, this
      novel chronic stress paradigm results in persistent alterations of hypothalamus
      pituitary-adrenal axis function and behavior, which are reversible by
      pharmacological treatment. Moreover, this paradigm allows to investigate the
      interaction of genetic susceptibility and environmental risk factors.

PMID- 17449189
TI  - Retrodifferentiation: a potential strategy for stem cell therapy of leukemic
      patients.

PMID- 17449190
TI  - Does the neuroprotective agent erythropoietin amplify diffuse axonal injury in
      its early stages?

PMID- 17449191
TI  - Possible role for interactions between 5-lipoxygenase (5-LOX) and AMPA GluR1
      receptors in depression and in antidepressant therapy.
AB  - Emerging evidence suggests that 5-lipoxygenase (5-LOX) plays a role in central
      nervous system functioning. It has been shown that 5-LOX metabolic products can
      decrease the phosphorylation of the glutamate receptor subunit GluR1, and that
      this effect can be antagonized by 5-LOX inhibitors. Recent concepts about the
      pathobiological mechanisms of depression and the molecular mechanisms of
      antidepressant activity postulate a significant role for glutamatergic
      neurotransmission and the GluR1 receptor. Regulation of GluR1 phosphorylation,
      i.e., enhancement of this phosphorylation, may be a part of antidepressant
      activity. On the other hand, reduced GluR1 phosphorylation may be a
      pathobiological mechanism contributing to depression. Since 5-LOX inhibitors,
      along with antidepressants share the capacity to increase GluR1 phosphorylation,
      we hypothesize that they may also have antidepressant properties. Furthermore, we
      postulate that increased brain 5-LOX expression may lead to decreased GluR1
      phosphorylation and favor the development of depression. For example, brain 5-LOX
      expression is stimulated by stress hormone glucocorticoids, and stress is a known
      contributing factor in depression.

PMID- 17449192
TI  - Extended neocortical maturation time encompasses speciation, fatty acid and
      lateralization theories of the evolution of schizophrenia and creativity.
AB  - I suggest that the extended maturation time of some regions of the human
      neocortex is the uniquely human factor which allows the development of language,
      creativity and madness. The genetic event or events which contribute to the long
      delay to final maturation occurred at or after the speciation of Homo sapiens
      sapiens. Neocortical growth may follow the previously detailed "balloon model",
      which suggests that intra- and subcortical myelin production during development
      physically stretches each local area of the cortex tangentially to the pial
      surface, thereby causing neuronal columns to become more disjoint and more
      functionally independent, thereby increasing the functional capacity of the area
      [Seldon HL. Does brain white matter growth expand the cortex like a balloon?
      Hypothesis and consequences. Laterality 2005;10(1):81-95]. This occurs in
      addition to Hebbian synaptic modeling. Therefore, the size and functional
      capacity of each cytoarchitectonic area of each individual adult neocortex are
      the outcomes of partly deterministic (e.g., genetic) and partly statistical
      growth processes with numerous factors including environmental stimuli and fatty
      acid content in diets. The possible functional capacity and variation among
      growth outcomes increase with the length of time allowed to "finalize" synaptic
      weights, myelination and other plastic processes. For example, acquisition of
      quite differing linguistic skills becomes possible only in Homo sapiens because
      of the extended, decades-long plasticity of temporal lobe areas; in contrast,
      tactile skills vary little among human races and cultures, or even among higher
      primates, because of the faster maturation of the somatomotor areas. Some of the
      statistically extreme variations of the neocortical growth processes lead to
      abnormal cognition and behavior called "madness" or "genius". This maturation
      hypothesis overcomes some problems with those based purely on fatty acid
      metabolism or on functional asymmetry (non-human species show functional
      asymmetry, but no language. Neanderthals had brains comparable in size and shape
      to ours, but failed to develop language or creativity). This hypothesis implies
      that the search for genetic factors should include those which influence the
      temporal regulation of neuronal and myelin growth, but it also allows the
      development of unusual creativity or madness as a statistical extreme in the
      absence of any deterministic factors. It has implications about our attitudes
      toward mental "disorders" and about potential approaches to treating some of them
      - for example, attempting communication and conditioning via those senses and
      cortical areas which show less variation and are less affected.

PMID- 17449193
TI  - Role of dynamic magnetic resonance imaging in the evaluation of tumor response to
      preoperative concurrent radiochemotherapy for large breast cancers: a prospective
      phase II study.
AB  - PURPOSE: To evaluate the accuracy of clinical examination and of three imaging
      modalities (ultrasound [US] scan, mammography, and magnetic resonance imaging
      [MRI]) to assess the tumor response of breast cancer to a preoperative regimen of
      concurrent radiochemotherapy for large breast cancers, using pathologic data as
      the reference. METHODS AND MATERIALS: Sixty women were accrued. Treatment
      consisted of 4 cycles of (5-fluorouracil-vinorelbine) chemotherapy with, starting
      with the second cycle of chemotherapy, locoregional radiotherapy to the breast
      and the internal mammary and supraclavicular and infraclavicular lymph nodes.
      Breast surgery and axillary lymph node dissection were subsequently performed.
      Breast imaging assessments were performed both before chemotherapy and
      preoperatively. RESULTS: The correlation coefficients between tumor dimension at
      imaging and pathology were statistically significant for US scan (r = 0.4; p =
      0.006) and MRI (r = 0.4; p = 0.004) but not for clinical examination (r = 0.2; p
      = 0.16) or mammography (r = -0.15; p = 0.31). Furthermore, the area under the
      receiver operating characteristic curve for MRI was 0.81, compared with 0.67 for
      US scan. At the optimal threshold score, MRI performed with 81% sensitivity and
      75% specificity. CONCLUSION: Compared with clinical examination, US scan, or
      mammography, MRI substantially improved the prediction of pathologic tumor
      response to preoperative concurrent radiochemotherapy for large breast cancers.

PMID- 17449194
TI  - Long-term prognostic effects of plasma epstein-barr virus DNA by minor groove
      binder-probe real-time quantitative PCR on nasopharyngeal carcinoma patients
      receiving concurrent chemoradiotherapy.
AB  - PURPOSE: To evaluate the long-term prognostic impact of plasma Epstein-Barr virus
      (EBV) DNA concentration measured by real-time quantitative polymerase chain
      reaction (RTQ-PCR) in nasopharyngeal carcinoma (NPC) patients receiving
      concurrent chemoradiotherapy (CCRT). METHODS AND MATERIALS: Epstein-Barr virus
      DNA was retrospectively measured from stock plasma of 152 biopsy-proven NPC
      patients with Stage II-IV (M0) disease with a RTQ-PCR using the minor groove
      binder-probe. All patients received CCRT with a median follow-up of 78 months. We
      divided patients into three subgroups: (1) low pretreatment EBV DNA (<1,500
      copies/mL) and undetectable posttreatment EBV DNA (pre-L/post-U), (2) high
      pretreatment EBV DNA (> or =1,500 copies/mL) and undetectable posttreatment EBV
      DNA (pre-H/post-U), and (3) low or high pretreatment EBV DNA and detectable
      posttreatment EBV DNA (pre-L or H/post-D) for prognostic analyses. RESULTS:
      Epstein-Barr virus DNA (median concentration, 573 copies/mL; interquartile range,
      197-3,074) was detected in the pretreatment plasma of 94.1% (143/152) of
      patients. After treatment, plasma EBV DNA decreased or remained 0 for all
      patients and was detectable in 31 patients (20.4%) with a median concentration 0
      copy/mL (interquartile range, 0-0). The 5-year overall survival rates of the pre
      L/post-U, pre-H/post-U, and pre-L or H/post-D subgroups were 87.2%, 71.0%, and
      38.7%, respectively (p < 0.0001). The relapse-free survival showed similar
      results with corresponding rates of 85.6%, 75.9%, and 26.9%, respectively (p <
      0.0001). Multivariate Cox analysis confirmed the superior effects of plasma EBV
      DNA compared to other clinical parameters in prognosis prediction. CONCLUSION:
      Plasma EBV DNA is the most valuable prognostic factor for NPC. More chemotherapy
      should be considered for patients with persistently detectable EBV DNA after
      CCRT.

PMID- 17449195
TI  - Physiologic and radiographic evidence of the distal edge of the proton beam in
      craniospinal irradiation.
AB  - PURPOSE: Fatty replacement of bone marrow resulting from radiation therapy can be
      seen on T1-weighted magnetic resonance (MR) images. We evaluated the radiographic
      appearance of the vertebral bodies in children treated with proton craniospinal
      irradiation (CSI) to illustrate the distal edge effect of proton radiotherapy.
      METHODS AND MATERIALS: The study cohort consisted of 13 adolescents aged 12-18
      years who received CSI with proton radiotherapy at Massachusetts General
      Hospital. Ten of these patients had reached maximal or near-maximal growth.
      Proton beam radiation for these 10 patients was delivered to the thecal sac and
      exiting nerve roots only, whereas the remaining 3 patients had a target volume
      that included the thecal sac, exiting nerve roots, and entire vertebral bodies.
      Median CSI dose was 27 [range, 23.4-36] cobalt gray equivalent (CGE) given in 1.8
      CGE fractions. Magnetic resonance images of the spine were obtained after
      completion of radiotherapy. RESULTS: Magnetic resonance images of patients who
      received proton radiotherapy to the thecal sac only demonstrate a sharp
      demarcation of hyperintense T1-weighted signal in the posterior aspects of the
      vertebral bodies, consistent with radiation-associated fatty marrow replacement.
      Magnetic resonance images of the patients prescribed proton radiotherapy to the
      entire vertebral column had corresponding hyperintense T1-weighted signal
      involving the entire vertebral bodies. CONCLUSION: The sharp delineation of
      radiation-associated fatty marrow replacement in the vertebral bodies
      demonstrates the rapid decrease in energy at the edge of the proton beam. This
      provides evidence for a sharp fall-off in radiation dose and supports the premise
      that proton radiotherapy spares normal tissues unnecessary irradiation.

PMID- 17449196
TI  - Nodal ratios in node-positive breast cancer--long-term study to clarify
      discrepancy of role of supraclavicular and axillary regional radiotherapy.
AB  - PURPOSE: To study the absolute number of involved nodes/the number of nodes
      examined or the nodal ratio (NR) in breast cancer. The primary study endpoint was
      to evaluate the role of supraclavicular and axillary radiotherapy (SART)
      according to the NR. METHODS AND MATERIALS: From the Saskatchewan provincial
      registry of 1981-1995, the charts of 5,996 consecutive patients were retrieved to
      collect detailed prognostic factors. Among these patients, 1,985 were node
      positive. Because the NRs are more reliable the greater the number of nodes
      examined, we analyzed 1,255 patients with > or =10 nodes examined. Of these 1,255
      patients, 667, 389, and 199 were categorized into three NR groups--low (< or
      =25%), medium (>25% to < or =75%), and high (>75%) nodal involvement,
      respectively. RESULTS: The NR correlated significantly with the primary tumor
      size (< or =2 cm, >2 to < or =5 cm, and >5 cm; p = 2.2 x 10(-16)), clinical stage
      group (p = 5.5 x 10(-16)), pathologic stage group (p < 2.2 x 10(-16)), and the
      risk of any first recurrence (p = 5.0 x 10(-15)) using chi-square tests. For a
      low NR, the 10-year overall survival rate with and without SART was 57% and 58%
      (p = 0.18), and the cause-specific survival rate was 68% and 71% (p = 0.32),
      respectively. For a medium NR, the 10-year overall survival rate with and without
      SART was 48% and 34% (p = 0.007), and the cause-specific survival rate was 57%
      and 43% (p = 0.002), respectively. For a high NR, the 10-year overall survival
      rate with and without SART was 19% and 10% (p = 0.005), and the cause-specific
      survival rate was 26% and 14% (p = 0.005), respectively. CONCLUSION: This is the
      first study demonstrating that for patients with > or =10 nodes examined, SART
      significantly improved the survival for the median and high NR groups but not for
      the low NR group.

PMID- 17449197
TI  - Radiation enterocolitis requiring surgery in patients with gynecological
      malignancies.
AB  - PURPOSE: To identify the characteristics, risk factors, and clinical outcomes of
      radiation enterocolitis requiring surgery in patients with gynecologic
      malignancies. METHODS AND MATERIALS: The records of 1,349 patients treated with
      pelvic radiotherapy were retrospectively reviewed. The majority of the patients
      (88%) were treated with 50 Gy or 50.4 Gy pelvic irradiation in conventional
      fractionations with anteroposterior fields. RESULTS: Forty-eight patients (3.6%)
      developed radiation enterocolitis requiring surgery. Terminal ileum was the most
      frequent site (50%) and most of the lesions had stenosis or perforation. On
      univariate analysis, previous abdominopelvic surgery, diabetes mellitus (DM),
      smoking and primary site had an impact on the complications, and on multivariate
      analysis, abdominopelvic surgery, DM, and smoking were independent predictors of
      the complications requiring surgery. After the surgical intervention, the
      frequency of Grade 2 or more bleeding was significantly lower in patients treated
      with intestinal resection in addition to decompression than those treated with
      intestinal decompression alone. CONCLUSIONS: Severe radiation enterocolitis
      requiring surgery usually occurred at the terminal ileum and was strongly
      correlated with previous abdominopelvic surgery, DM, and smoking. Concerning the
      management, liberal resection of the affected bowel appears to be the preferable
      therapy.

PMID- 17449198
TI  - Homologs of eukaryotic Ras superfamily proteins in prokaryotes and their novel
      phylogenetic correlation with their eukaryotic analogs.
AB  - Ras superfamily proteins are key regulators in a wide variety of cellular
      processes. Previously, they were considered to be specific to eukaryotes, and
      MglA, a group of obviously different prokaryotic proteins, were recognized as
      their only prokaryotic analogs or even ancestors. Here, taking advantage of quite
      a current accumulation of prokaryotic genomic databases, we have investigated the
      existence and taxonomic distribution of Ras superfamily protein homologs in a
      much wider prokaryotic range, and analyzed their phylogenetic correlation with
      their eukaryotic analogs. Thirteen unambiguous prokaryotic homologs, which
      possess the GDP/GTP-binding domain with all the five characteristic motifs of
      their eukaryotic analogs, were identified in 12 eubacteria and one
      archaebacterium, respectively. In some other archaebacteria, including four
      methanogenic archaebacteria and three Thermoplasmales, homologs were also found,
      but with the GDP/GTP-binding domains not containing all the five characteristic
      motifs. Many more MglA orthologs were identified than in previous studies mainly
      in delta-proteobacteria, and all were shown to have common unique features
      distinct from the Ras superfamily proteins. Our phylogenetic analysis indicated
      eukaryotic Rab, Ran, Ras, and Rho families have the closest phylogenetic
      correlation with the 13 unambiguous prokaryotic homologs, whereas the other three
      eukaryotic protein families (SRbeta, Sar1, and Arf) branch separately from them,
      but have a relatively close relationship with the methanogenic archaebacterial
      homologs and MglA. Although homologs were identified in a relative minority of
      prokaryotes with genomic databases, their presence in a relatively wide variety
      of lineages, their unique sequence characters distinct from those of eukaryotic
      analogs, and the topology of our phylogenetic tree altogether do not support
      their origin from eukaryotes as a result of lateral gene transfer. Therefore, we
      argue that Ras superfamily proteins might have already emerged at least in some
      prokaryotic lineages, and that the seven eukaryotic protein families of the Ras
      superfamily may have two independent prokaryotic origins, probably reflecting the
      'fusion' evolutionary history of the eukaryotic cell.

PMID- 17449199
TI  - Selection and validation of optimal siRNA target sites for RNAi-mediated gene
      silencing.
AB  - RNA interference (RNAi)-mediated gene silencing has become a valuable tool for
      functional studies, reverse genomics, and drug discoveries. One major challenge
      of using RNAi is to identify the most effective short interfering RNAs (siRNAs)
      sites of a given gene. Although several published bioinformatic prediction models
      have proven useful, the process to select and validate optimal siRNA sites for a
      given gene remains empirical and laborious. Here, we developed a fluorescence
      based selection system using a retroviral vector backbone, namely pSOS, which was
      based on the premise that candidate siRNAs would knockdown the chimeric
      transcript between GFP and target gene. The expression of siRNA was driven by the
      opposing convergent H1 and U6 promoters. This configuration simplifies the
      cloning of duplex siRNA oligonucleotide cassettes. We demonstrated that GFP
      signal reduction was closely correlated with siRNA knockdown efficiency of human
      beta-catenin, as well as with the inhibition of beta-catenin/Tcf4 signaling
      activity. The pSOS should not only facilitate the selection and validation of
      candidate siRNA sites, but also provide efficient delivery tools of siRNAs via
      viral vectors in mammalian cells. Thus, the pSOS system represents an efficient
      and user-friendly strategy to select and validate siRNA target sites.

PMID- 17449200
TI  - Molecular phylogenetic study on the origin and evolution of Mustelidae.
AB  - The family Mustelidae, which consists of Mustelinae, Lutrinae, Melinae, and
      Taxidiinae, is the largest family among Carnivora and is a highly diverse group.
      Recent molecular phylogenetic studies have clarified the phylogenetic relations
      among Mustelidae, but there remain several unresolved problems, particularly
      concerning the deep branchings. Whereas many studies support the monophyly of
      Mustelidae+Procyonidae among Musteloidea, the relations between
      Mustelidae+Procyonidae, Ailuridae, and Miphitidae are still unclear. To address
      these problems, we inferred a tree on the basis of the sequences of mitochondrial
      genomes and of multiple nuclear genes using the maximum likelihood method. Our
      results strongly support the hypothesis that the Taxidiinae branched at first,
      followed by the branching of the Melinae. After that, Mustelinae diversified, and
      Lutrinae evolved within Mustelinae. With respect to the deep branchings in
      Musteloidea, the Ailuridae/Mephitidae monophyly tree and the Mephitidae-basal
      tree are indistinguishable in log-likelihood score, and this problem remains
      unresolved.

PMID- 17449201
TI  - Rapidly evolving lamins in a chordate, Oikopleura dioica, with unusual nuclear
      architecture.
AB  - Metazoan lamins are implicated in the organization of numerous critical nuclear
      processes. Among chordates, the appendicularian, Oikopleura dioica, has an
      unusually short life cycle involving rapid growth through extensive recourse to
      endoreduplication, a characteristic more associated with some invertebrates. In
      some tissues, this is accompanied by the formation of elaborate, bilaterally
      symmetric nuclear morphologies associated with specific gene expression patterns.
      Lamin composition can mediate nuclear shape in spermiogenesis as well as during
      pathological and normal aging and we have analyzed the O. dioica lamin and
      intermediate filament (IF) complement, comparing it to that present in other
      deuterostomes. O. dioica has one lamin gene coding two splice variants. Both
      variants share with the sister class ascidians a highly reduced C-terminal tail
      region lacking the immunoglobulin fold, indicating this derivation occurred at
      the base of the urochordate lineage. The OdLamin2 variant has a unique insertion
      of 63 amino acids in the normally short N-terminal region and has a developmental
      expression profile corresponding to the occurrence of endocycling. O. dioica has
      4 cytoplasmic IF proteins, IF-A, C, Dalpha, and Dbeta. No homologues to the
      ascidian IF-B or F proteins were identified, reinforcing the suggestion that
      these proteins are unique to ascidians. The degree of sequence evolution in the
      rod domains of O. dioica cytoplasmic IF proteins and their closest ascidian and
      vertebrate homologues was similar. In contrast, whereas the rate of lamin B rod
      domain sequence evolution has also been similar in vertebrates, cephalochordates
      and the sea urchin, faster rates have occurred among the urochordates, with the
      O. dioica lamin displaying a far greater rate than any other lamin.

PMID- 17449202
TI  - Susceptibility of domestic dogs and cats to Australian bat lyssavirus (ABLV).
AB  - The susceptibility of cats and dogs to Australian bat lyssavirus (ABLV; genotype
      VII) was investigated by intramuscular (IM) inoculation of 10(3.7)-10(5) 50%
      tissue culture infective doses (TCID(50)) of virus followed by observation of
      experimental animals for up to 3 months post-inoculation (pi). Each experiment
      also included positive and negative controls, animals inoculated with a bat
      variant of rabies virus (Eptesicus I, genotype I), or a 10% suspension of
      uninfected mouse brain, respectively. Each of the ABLV-inoculated cats showed
      occasional abnormal clinical signs, but none died. Necropsies performed at 3
      months pi revealed no lesions, and no viral antigen, in the central nervous
      system of any cat. ABLV could not be recovered from any cats. However, rabies
      virus-neutralizing antibodies were detected between 4 and 14 weeks pi in the sera
      of all three ABLV-inoculated cats. At 2-3 weeks pi, three of the five ABLV
      inoculated dogs showed very mild abnormal clinical signs that persisted for 1-2
      days, after which the dogs recovered. At 3 months pi, when all dogs were
      necropsied, neither lesions nor ABLV antigen were detected in, and virus was not
      isolated from, any dog. No ABLV RNA was detected by polymerase chain reaction
      (PCR) in clinical or necropsy samples from the three ABLV-affected dogs. However,
      all ABLV-inoculated dogs seroconverted by 2 weeks pi, and serum antibody titres
      were higher than those observed in cats. CSF, collected at 3 months pi, was
      positive for rabies virus-neutralizing antibody in two ABLV-inoculated dogs.

PMID- 17449203
TI  - Curcumin activates human glutathione S-transferase P1 expression through
      antioxidant response element.
AB  - Curcumin is a plant-derived diferuloylmethane compound extracted from Curcuma
      longa, possessing antioxidative and anticarcinogenic properties. Antioxidants and
      oxidative stress are known to induce the expression of certain classes of
      detoxification enzymes. Since the upregulation of detoxifying enzymes affects the
      drug metabolism and cell defense system, it is important to understand the gene
      regulation by such agents. In this study, we demonstrated that curcumin could
      induce the expression of human glutathione S-transferase P1 (GSTP1). In HepG2
      cells treated with 20muM curcumin, the level of GSTP1 mRNA was significantly
      increased. In luciferase reporter assays, curcumin augmented the promoter
      activity of a reporter construct carrying 336bp upstream of the 5'-flanking
      region of the GSTP1 gene. Mutation analyses revealed that the region including
      antioxidant response element (ARE), which overlaps AP1 in sequence, was essential
      to the response to curcumin. While the introduction of a wild-type Nrf2
      expression construct augmented the promoter activity of the GSTP1 gene, co
      expression of a dominant-negative Nrf2 abolished the responsiveness to curcumin.
      In addition, curcumin activated the expression of the luciferase gene from a
      reporter construct carrying multiple ARE consensus sequences but not one with
      multiple AP1 sites. In a gel mobility shift assay with an oligonucleotide with
      GSTP1 ARE, an increase in the amount of the binding complex was observed in the
      nuclear extracts of curcumin-treated HepG2 cells. These results suggested that
      ARE is the primary sequence for the curcumin-induced transactivation of the GSTP1
      gene. The induction of GSTP1 may be one of the mechanisms underlying the multiple
      actions of curcumin.

PMID- 17449204
TI  - Effect of slow freezing on morphology and developmental competence of buffalo
      (Bubalus bubalis) immature oocytes.
AB  - The present study was conducted to evaluate the effects of three cryoprotectants,
      dimethyl sulphoxide (DMSO), ethylene glycol (EG) and 1,2-propanediol (PROH), each
      used at two concentrations (1.0 and 1.5 M) on the morphology, maturation rate and
      developmental capacity of usable quality immature buffalo oocytes subjected to
      slow freezing. The addition of the cryoprotectant before freezing and its
      dilution after thawing were carried out in a two- (for 1.0 M) or three-step
      manner (for 1.5 M). The incidence of damage was found to be significantly higher
      (P<0.05) with the lower concentration of 1.0 M, compared to that with 1.5 M for
      all the three cryoprotectants examined. The proportion of immature oocytes
      recovered in a morphologically normal state was significantly higher (P<0.05) for
      DMSO than those for EG or PROH at both 1.0 and 1.5 M concentrations. Among the
      six combinations evaluated, that of DMSO at 1.5 M concentration was found to be
      superior to others. Irrespective of the type or concentration of the
      cryoprotectant, partial or complete loss of the cumulus mass was the most
      prevalent damage. Following in vitro maturation, the nuclear maturation rate was
      significantly higher (P<0.05) for DMSO than those for EG or PROH at both 1.0 and
      1.5 M concentrations. When the in vitro matured oocytes were subjected to in
      vitro fertilization after slow freezing, using 1.5 M DMSO as cryoprotectant, 4.5%
      and 0.6% of them were able to develop to morulae and blastocysts, respectively,
      on Day 9 post insemination, compared to 19.2% and 10.6%, respectively, for the
      controls. In conclusion, DMSO was more effective than EG or PROH for the slow
      freezing of immature buffalo oocytes and blastocysts could be produced from
      immature buffalo oocytes subjected to slow freezing in 1.5 M DMSO.

PMID- 17449205
TI  - Effects of the Booroola (FecB) genotypes on growth performance, ewe's
      productivity efficiency and litter size in Garole x Malpura sheep.
AB  - The present study was conducted to evaluate the effects of FecB genotypes on body
      weight, average daily gain (ADG), ewe's productivity efficiency (EPE) and litter
      size in FecB introgressed GarolexMalpura (GM) crossbred sheep. A total of 235 GM
      lambs were selected randomly and screened for FecB mutation using forced RFLP
      PCR. The majority (69.8%) of GM individuals were carriers (BB and B+) for the
      FecB mutation and frequency of the FecB allele was about 0.40. The FecB genotypes
      were significantly (P<0.01) associated with the lamb's body weights from birth to
      12 months of age. The generation wise (F(1), F(2) and F(3)), lamb's body weight
      did not differ significantly at birth, 6 and 12 months of the age, while it
      differed significantly (P<0.05) at 3 and 9 months of age. The ADG1 (0-3 months)
      was significantly associated (P<0.05), but not the ADG2 (3-6 months) and ADG3 (6
      12 months) between genotypes. Type of birth and sex significantly (P<0.01)
      affected the body weight from birth to 12 months of age; and body weight of
      single born lambs was significantly higher (P<0.01) than that of twins and
      triplets from birth to 12 months of age. Type of birth significantly (P<0.01)
      affected the ADG1, but had no significant effect on ADG2 and ADG3. Year of birth
      did not affect the birth and weaning weights, but it significantly affected
      (P<0.01) the body weight and ADG's after weaning ages. The EPE was affected
      significantly (P<0.01) by the FecB genotypes at birth, 3 and 12 months of age.
      The EPE of B+ and BB ewes were 7.86 kg (36.9%) and 2.32 kg (10.9%) higher as
      compared to ++ ewes at 12 months of age, respectively. The mean litter size of BB
      ewes (2.17+/-0.24) was significantly higher (P<0.01) than that of B+ ewes (1.73+/
      0.04) and ++ ewes (1.03+/-0.23). The present study indicated that the body weight
      and ADG of carrier lambs (BB and B+) was comparatively lower than that of non
      carriers (++), while EPE of B+ ewes was comparatively higher than that of BB and
      ++ ewes. Further, it is interesting to note that heterozygous and homozygous
      state of individuals increased 0.70 and 1.14 extra lambs as compared to non
      carriers (++), respectively.

PMID- 17449206
TI  - Effect of the environment on the physiology of the sow during late pregnancy,
      farrowing and early lactation.
AB  - We investigated the effect of two types of housing on the duration of farrowing
      and the physiology of sows before and after farrowing. We assigned 20 sows (PEN)
      to farrowing pens (210 cm x 335 cm) enriched with straw bedding and 18 sows
      (CRATE) were placed in farrowing crates (80 cm x 210 cm) with no bedding
      material. We sampled the animals during period A (from day -5 before farrowing to
      day +1 of lactation) and during period B (from days +2 to +5 of lactation). We
      took daily venous blood samples for progesterone measurements and four salivary
      samples per day (at 09:00, 11:00, 13:00 and 15:00) for cortisol determination. In
      addition, intensive blood sampling was performed in 18 catheterised sows (9 PEN
      and 9 CRATE) to determine the level of oxytocin during farrowing. The treatment
      had no effect on litter size, piglet mortality at birth and weaning, growth of
      the piglets between days 1 and 5 of life. We found no significant difference in
      the cortisol concentration between the two groups during period A (p=0.36).
      Significant difference was found in period B, where the CRATE group had a higher
      concentration of cortisol than the PEN group (p=0.03). Progesterone concentration
      did not differ between the two groups (p=0.80). The duration of farrowing was on
      average 93 min longer in the CRATE sows (n=15), with a mean of 311+/-35 min
      (mean+/-S.D.), than in the PEN sows (n=19), with a mean of 218+/-24 min (p=0.03).
      In addition, the mean interval between each piglet expulsion was longer in the
      CRATE group (n=11), with a mean of 25+/-4 min, than in the PEN group (n=15) with
      a mean of 16+/-2 min (p=0.05). During farrowing, the post-expulsion oxytocin
      pulses average tended to be higher in the PEN group (77.6+/-47.6 ng/ml) than in
      the CRATE group (38.1+/-24.6 pg/ml) (p=0.08). The concentration of oxytocin
      strongly affected the duration of farrowing (p<0.001). In conclusion, this study
      showed that the environment influences the physiology of the sow during farrowing
      and early lactation.

PMID- 17449207
TI  - Avidin bioconjugate with a thermoresponsive polymer for biological and
      pharmaceutical applications.
AB  - A thermoresponsive polymer, N-isopropylacrylamide-co-acrylamide (Mn 6 kDa) with a
      lower critical solution temperature (LCST) of 37 degrees C, was activated and
      conjugated to avidin to yield a derivative with 200 kDa molecular weight. Gel
      permeation analysis demonstrated that the new bioconjugate possessed an apparent
      size corresponding to a 220 kDa globular protein. Photon correlation spectroscopy
      and turbidometric studies showed that the bioconjugate underwent temperature
      dependent phase transitions. The protein-co-polymer bioconjugate displayed the
      same onset phase transition temperature (LCST) as the original synthetic co
      polymer. Nevertheless, the aggregation profile of the bioconjugate shifted at
      higher temperature as compared to the original polymer. This indicated that the
      aggregation behaviour coil-to-globule transition of the co-polymer was modified
      by anchoring to the protein surface. Circular dichroism analysis showed that the
      co-polymer conjugation did not alter the protein tertiary structure tertiary the
      aromatic amino acid environment. The bioconjugate maintained 85+/-3% of native
      avidin affinity for biotin and biotin-Mab, and high affinity was maintained after
      three heating cycles. Pharmacokinetic studies demonstrated that the co-polymer
      bioconjugation increased the avidin residence time in the bloodstream. The
      distribution phase of avidin-co-polymer was longer than the native protein by a
      factor of 20. The co-polymer conjugation decreased by three-fold the distribution
      extent of avidin and reduced significantly its up-take to the liver.

PMID- 17449208
TI  - Joint match probabilities for Y chromosomal and autosomal markers.
AB  - Empirical tests of association between Y chromosome and autosomal markers are
      presented and a theoretical framework for determining a joint match probability
      is recommended. Statistical analyses of association were performed in 16 US
      populations between the autosomal genotypes from loci CSF1PO, FGA, THO1, TPOX,
      vWA, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S512, D21S11 and Y
      chromosome haplotypes from loci DYS19, DYS385ab, DYS389I, DYS389II, DYS390,
      DYS391, DYS392, DYS393, DYS438, and DYS439. The sample populations include
      individuals of European-, African-, Hispanic-, Native-, and Asian-American
      ancestry. The results are consistent with independence of Y and autosomal
      markers, although small amounts of dependence would likely have escaped our
      tests. Given the data in hand, we suggest it is appropriate to compute joint
      match probabilities by multiplying the Y haplotype frequency with the
      appropriately corrected autosomal frequency. In addition to correcting for
      autosomal frequency differences between groups, a further correction may be
      required. Since two individuals sharing the same Y haplotype are likely to be
      more recently related than two randomly chosen individuals, the autosomal
      frequencies have to be adjusted to account for this, akin to the theta correction
      used to account for population substructure. The structure imposed on the
      autosomal frequencies conditioned in a Y match is a function of the number of
      markers scored and their mutation rate. However, in most settings theta<0.01.
      When population structure is already present in the autosomes, the additional
      effect due to conditioning on the Y is small. For example, if the amount of
      structure in the population is theta=0.01 or 0.03 (the NRCII range), then the
      effect of conditioning on the Y results in only a trivial increase in theta to
      0.02-0.04, respectively.

PMID- 17449209
TI  - Cloning and sequencing of the class A beta-lactamase gene (blaTEM-15) located on
      a chromosomal Tn801 transposon.
AB  - Escherichia coli CA0210 was identified in a stool culture of a 03-month-neonate
      in Tunisia. This strain was resistant to beta-lactams, including
      ureidopenicillins, ticarcillin-clavulanic acid, cefpirome, ceftazidime, and
      cefotaxime, but it remained susceptible to imipenem and cefoxitin. The beta
      lactam-hydrolyzing beta-lactamase gene of E. coli CA0210 and the upstream and
      downstream regions were cloned, sequenced, and expressed in E. coli DH5alpha.
      These resistances were carried by a 1080-bp chromosomal gene that encoded a beta
      lactamase with a pI of 6.3. Cloning and sequencing experiments showed that the
      corresponding blaTEM-15 gene was part of a chromosomally located Tn801
      transposon.

PMID- 17449210
TI  - Cross-over assessment of serum bactericidal activity of moxifloxacin and
      levofloxacin versus penicillin-susceptible and penicillin-resistant Streptococcus
      pneumoniae in healthy volunteers.
AB  - We compared the serum bactericidal activity (SBA) of moxifloxacin and
      levofloxacin against penicillin-susceptible and penicillin-resistant
      Streptococcus pneumoniae in 12 healthy volunteers. Each subject received 3 days
      of oral moxifloxacin 400 mg daily and levofloxacin 750 mg daily, respectively,
      with a 2- to 4-week washout period between regimens. Blood was drawn at 6 time
      points after the third dose of each antibiotic. Mean serum bactericidal titers
      (MSBTRs) for moxifloxacin were 4-fold higher than the mean titers for
      levofloxacin at each time point. For each drug, MSBTRs at each time point were
      the same or within one 2-fold dilution when analyzed according to the penicillin
      susceptibility of the strains or the sex of the subjects. The difference in SBA
      of the 2 drugs may have implications for the emergence of resistance and clinical
      outcome.

PMID- 17449211
TI  - The emergence of a novel ceftazidime-resistant CTX-M extended-spectrum beta
      lactamase, CTX-M-55, in both community-onset and hospital-acquired infections in
      Thailand.
AB  - We report a novel CTX-M type of extended-spectrum beta-lactamase (ESBL),
      designated CTX-M-55, among 7 patients who had infection with ESBL-producing
      Escherichia coli or Klebsiella pneumoniae at a university hospital in Thailand.
      The CTX-M-55 ESBL showed reduced susceptibility to ceftazidime. This
      investigation provides the relevant clinical and molecular epidemiology for the
      gene encoding for CTX-M-55 in the isolates from these patients.

PMID- 17449212
TI  - In vitro activity of ceftobiprole, daptomycin, linezolid, and vancomycin against
      methicillin-resistant staphylococci associated with endocarditis and bone and
      joint infection.
AB  - We tested the in vitro activity of 4 antimicrobial agents against methicillin
      resistant Staphylococcus aureus and coagulase-negative staphylococci recovered
      from patients with endocarditis or bone and joint infection. Ceftobiprole,
      daptomycin, linezolid, and vancomycin MIC(90) values were 1, 1, 2, and 1
      microg/mL, respectively. Ceftobiprole, daptomycin, linezolid, and vancomycin
      MBC(90) values were 2, 4, > or = 128, and 8 microg/mL, respectively. Ceftobiprole
      MIC and MBC values were < or = 2 microg/mL for all isolates tested, with the
      exception of one methicillin-resistant coagulase-negative Staphylococcus spp
      isolate. Vancomycin lacked bactericidal activity (defined as an MBC/MIC ratio of
      > or = 32) against 2 methicillin-resistant Staphylococcus aureus (MRSA) isolates
      from patients with bone and joint infection; one of these isolates was
      additionally daptomycin nonsusceptible (daptomycin MIC, 2 microg/mL). There was
      one additional daptomycin nonsusceptible (daptomycin MIC, 2 microg/mL) isolate
      (MRSA associated with bone and joint infection). Ceftobiprole demonstrated in
      vitro bactericidal activity against all MRSA and methicillin-resistant coagulase
      negative staphylococci tested.

PMID- 17449213
TI  - Evaluation of colony-based examinations of diarrheagenic Escherichia coli in
      stool specimens: low probability of detection because of low concentrations,
      particularly during the early stage of gastroenteritis.
AB  - To evaluate traditional colony-based examinations of diarrheagenic Escherichia
      coli (DEC), we analyzed the proportions of 5 categories of DEC among E. coli in
      stool specimens from patients with gastroenteritis using real-time polymerase
      chain reaction with novel primers and probes. Among 81 DEC isolates, 48 (59.3%)
      were present at proportions of < or = 10%, whereas only 17 (21.0%) reached >50%.
      Low concentrations (< or = 10%) of DEC were found, particularly in most (71.8%)
      stool specimens collected within 48 h after the onset of illness, although such
      specimens were conventionally collected as close to the time of diarrhea onset as
      possible. Because the probability of detecting < or = 10% DEC by colony-based
      examinations is very low, traditional laboratory methods might not detect most
      DEC infections, especially at the start of gastroenteritis. Thus, a diagnosis of
      DEC infections requires a molecular method that targets not individual colonies
      but E. coli clusters.

PMID- 17449214
TI  - Age-related changes in urinary bladder intramural neurons.
AB  - A quantitative morphometric evaluation of the intramural plexus of the urinary
      bladder of adult and aged guinea-pigs was performed by histological analysis,
      scanning electron microscopy, and hystochemical methods, such as NADH-diaphorase
      and acetylcholinesterase (AChE). The round or oval shaped intramural neurons were
      revealed among the bundles of the smooth detrusor muscle in clusters containing a
      variable number of cells in the groups. In both adult control and aged animals,
      the ganglia were enveloped by a ganglionar capsule of connective tissue mainly
      composed of type I collagen fibers. The number of neurons NADH-diaphorase
      positives estimated in the intramural plexus was 1433+/-187.71 and 1107+/-120.67
      in the adult control and aged groups, respectively. The perikaryon areas of the
      NADH-diaphorase neurons reactives ranged from 216.40 to 1809.30 microm(2) in
      adult control group and from 198.20 to 2096.25 microm(2) in aged group. The
      nuclear area showed an increase in aged animals. The number of AChE-positive
      neurons estimated in the intramural plexus was 3294.67+/-415 microm(2) in the
      adult control group and 1960.33+/-526 microm(2) in the aged group, showing a
      significant decrease in the latter group. This age-related morphological change
      in intramural neurons may contribute to changes in urinary bladder activities in
      the elderly.

PMID- 17449215
TI  - Dilemmas in the (un)veiling of the diagnosis of Alzheimer's disease: walking an
      ethical and professional tight rope.
AB  - OBJECTIVE: To enhance the understanding and effect of physician's difficulties,
      attitudes and communication styles on the disclosure of the diagnosis of AD in
      practice. METHODS: Qualitative, phenomenological study, combining pre-encounter
      interviews with physicians, observations of actual encounters of diagnosis
      disclosure of AD, and post-encounter interviews. RESULTS: There were various ways
      or tactics to (un)veil the bad news that may be perceived as different ways of
      dulling the impact and avoiding full and therefore problematic statements. In the
      actual encounters this was accomplished by keeping encounters short, avoiding
      elaboration, confirmation of comprehension and explicit terminology and using
      fractured sentences. CONCLUSION: The present study's findings highlight the
      difficulties encountered in breaking the news about AD, in the way it is actually
      done, and the problems that may arise from this way of un/veiling the news. The
      main problem is that the reluctance to make a candid disclosure of the diagnosis
      as was demonstrated in this study may violate basic moral and legal rights and
      may also deprive patients and caregivers of some of the benefits of early
      disclosure of diagnosis. PRACTICE IMPLICATIONS: There is a need for assisting
      physicians to cope with their personal difficulties, problems and pitfalls in
      breaking the news.

PMID- 17449216
TI  - HIV seropositive drug users' attitudes towards partner notification (PCRS):
      results from the SHIELD study in Baltimore, Maryland.
AB  - OBJECTIVE: To assess the attitudes of HIV seropositive current or former drug
      users towards HIV partner counseling and referral services (PCRS) and to
      determine if opinion varies by partner type. METHODS: We used a cross-sectional
      survey using structured and semi-structured questions to measure attitudes
      towards PCRS. RESULTS: The majority of the sample was African-American (97%),
      male (63%) and had been diagnosed with HIV for a mean of 7.9 years. Most agreed
      that PCRS would help stop the spread of HIV and AIDS (87%). A range of reactions
      to scenarios of their drug and sex partners being informed were observed and
      included positive reactions (e.g. PCRS as a means to facilitate testing of their
      partners and early treatment) to negative (e.g. feelings about guilt, shame and
      concern about partner responses). CONCLUSION: Data from this study indicate that
      HIV positive drug users view PCRS as a viable practice for preventing the spread
      of HIV, though barriers exist to engaging clients to identify partners. PRACTICE
      IMPLICATIONS: The range of reactions noted in this study underscore the
      importance of providing flexible options for PCRS based on partner type.
      Additional training for counselors, time for case-management and meetings with
      sex and drug partners and fieldwork for locating contacts are important
      considerations for providers.

PMID- 17449217
TI  - The characteristics and failure pattern of gefitinib responders with
      postoperative recurrence of pulmonary adenocarcinoma.
AB  - AIMS: Gefitinib shows prominent anti-tumor activity against advanced or recurrent
      non-small cell lung cancer (NSCLC). However, most gefitinib-responsive patients
      ultimately relapse. We reviewed postoperatively recurrent NSCLC patients who
      received gefitinib treatment, and analyzed both the clinical features and
      manifestations of treatment failure in patients who initially responded to
      gefitinib. METHODS: From 2002 to 2006, gefitinib was administered to in 34
      postoperative recurrent lung adenocarcinoma patients. There were 13 men and 21
      women with a mean age of 65 years. Twenty patients had never smoked while 14 were
      former smokers. Epidermal growth factor receptor (EGFR) gene mutation was
      measured using surgical specimens of the primary tumor. RESULTS: The study group
      showed 1 complete response, 16 partial responses, 7 stable diseases and 8
      progressive diseases. Mutations of EGFR gene were detected in 20 of 34 patients.
      Only the presence of EGFR gene mutations was significantly associated with the
      clinical response of gefitinib in our limited study (p=0.036). In 9 of 12
      responders, gefitinib treatment failed due to the appearance of new lesions.
      CONCLUSIONS: Gefitinib was significantly effective for patients with mutations of
      the EGFR gene and most responders failed due to the appearance of new lesions
      without progression of the pre-existent target lesions.

PMID- 17449218
TI  - Ex vivo sentinel lymph node "mapping" in colorectal cancer.
AB  - BACKGROUND: The purpose of this study was to evaluate the feasibility and
      reliability of ex vivo sentinel lymph node mapping in patients with colorectal
      cancer. METHODS: In the period January-June 2006, 44 consecutive patients
      underwent curative surgery for colorectal cancer. In patients with colon and
      rectal cancer, 0.5-2 ml of Patent Blue Dye was injected submucosally. The
      injection sites where then gently massaged for 5 min. RESULTS: In 96% of the
      patients with colon cancer and 94% of the patients with rectal cancer, at least
      one sentinel lymph node was found. There were no patients with a false negative
      sentinel node. The sensitivity was 100% with a negative predictive value of 100%.
      In 19% of the patients with colon cancer and 18% of the patients with rectal
      cancer the sentinel node was the exclusive site of lymph node metastases. After
      additional sectioning and staining, 7 of the 23 patients (30%) with a Dukes B
      colorectal cancer were upstaged. CONCLUSION: The technique of ex vivo sentinel
      lymph node mapping is technically feasible with high sensitivity, high negative
      predictive value and a high rate of upstaging. The next step is to investigate,
      if detection of micro-metastases is associated with decreased survival and/or
      increased local recurrence rates.

PMID- 17449219
TI  - [Good clinical practices and inpatient antibiotics: optimization of
      fluoroquinolone switch therapy].
AB  - OBJECTIVE: Intravenous-to-oral switch therapy is strongly recommended in the
      medical literature. The aim of this study was to assess how we can improve
      fluoroquinolone switch therapy. METHODS: In this comparative prospective study,
      we analyzed 243 intravenous ciprofloxacin treatments and assessed the impact of
      promoting a switch to oral step-down therapy. RESULTS: This study found that
      switches from intravenous to oral therapy increased, mainly in medical wards, and
      led to significant savings in direct costs. DISCUSSION: Promoting switch therapy
      has improved clinical practices in antibiotic use and led to lower direct and
      probably indirect drug-related costs. CONCLUSION: Our findings will help define
      the role of switch therapy in improving clinical practices in inpatient
      antibiotic use.

PMID- 17449220
TI  - Sleep-based heart period variability in panic disorder with and without nocturnal
      panic attacks.
AB  - In this paper, we investigated ambulatory sleep heart period variability in panic
      disorder participants with nocturnal panic (NP) compared to daytime panic attacks
      only. A time-derived measure of heart period variability (HPV) during sleep was
      significantly reduced in the NP group (n=32) relative to the daytime panic (n=17)
      and nonanxious (n=17) control groups. Consistent with previous work, NP
      participants also reported greater fear of relaxation and sleep than daytime
      panic and control groups. Based on a neurovisceral model of attention [Thayer, J.
      F., & Lane, R. D. (2000). A model of neurovisceral integration in emotion
      regulation and dysregulation. Journal of Affective Disorders, 61, 210-216] that
      predicts that decreased HPV is related to disregulated behavioral adaptation, we
      hypothesized that HPV measured during sleep would be most reduced in NP
      participants. These findings indicate that HPV is related to nocturnal panic
      disorder insofar as it is measured during sleep.

PMID- 17449221
TI  - Anxiety sensitivity and affect regulatory strategies: individual and interactive
      risk factors for anxiety-related symptoms.
AB  - Studies have shown that anxiety sensitivity (AS) is a risk factor in the
      development of pathological anxiety. Recent theoretical models emphasize the
      additional importance of how people handle their anxious experiences. The present
      study examined whether high AS and being fixated on the control and regulation of
      unwanted anxious feelings or being unable to properly modulate affect as needed
      lead to particularly problematic outcomes. We examined the interactive influence
      of AS and affect regulatory strategies on the frequency and intensity of anxiety
      symptoms. Questionnaires were completed by 248 young adults in the community.
      Results showed a general pattern with anxiety symptoms being the most severe when
      high AS was paired with affect regulatory difficulties. Of participants high in
      AS, anxious arousal and worry were heightened in the presence of less acceptance
      of emotional distress; anxious arousal, worry, and agoraphobic cognitions were
      heightened when fewer resources were available to properly modulate affect; and
      agoraphobic cognitions were heightened in the presence of high emotion
      expressiveness. As evidence of construct specificity, an alternative model with
      anhedonic depressive symptoms as a main effect and interaction effect (with
      regulatory strategies) failed to predict anxiety symptoms. However, anxiety
      sensitivity and less acceptance of emotional distress were associated with
      greater anhedonia. Results are discussed in the context of how and when affect
      regulatory behavior shifts individuals from normative anxiety to pathology.

PMID- 17449222
TI  - Flow-cytometric analysis of mouse embryonic stem cell lipofection using small and
      large DNA constructs.
AB  - Using the lipofection reagent LipofectAMINE 2000 we have examined the delivery of
      plasmid DNA (5-200 kb) to mouse embryonic stem (mES) cells by flow cytometry. To
      follow the physical uptake of lipoplexes we labeled DNA molecules with the
      fluorescent dye TOTO-1. In parallel, expression of an EGFP reporter cassette in
      constructs of different sizes was used as a measure of nuclear delivery. The
      cellular uptake of DNA lipoplexes is dependent on the uptake competence of mES
      cells, but it is largely independent of DNA size. In contrast, nuclear delivery
      was reduced with increasing plasmid size. In addition, linear DNA is transfected
      with lower efficiency than circular DNA. Inefficient cytoplasmic trafficking
      appears to be the main limitation in the nonviral delivery of large DNA
      constructs to the nucleus of mES cells. Overcoming this limitation should greatly
      facilitate functional studies with large genomic fragments in embryonic stem
      cells.

PMID- 17449223
TI  - Neonatal immune system activation with lipopolysaccharide enhances behavioural
      sensitization to the dopamine agonist, quinpirole, in adult female but not male
      rats.
AB  - Administration of the bacterial cell wall component, lipopolysaccharide (LPS),
      stimulates the immune and endocrine systems inducing an acute phase of sickness
      and stress responses in adult and neonatal rats. Neonatal LPS exposure has been
      shown to alter a variety of behavioural and physiological processes in the adult
      animal. Early developmental stress, such as maternal separation, causes similar
      acute as well as long-term behavioural changes in adults, including altered
      sensitivity to drugs of abuse. Moreover, results of studies have shown evidence
      of a direct link between immune activation and sensitivity to dopamine-based
      drugs of abuse. The current study examined the effects of neonatal LPS treatment
      on subsequent locomotor sensitization to the dopamine (D(2)/D(3)) agonist,
      quinpirole, in adult rats as an index of drug sensitivity. Male and female Long
      Evans rats were treated systemically with either LPS (50microg/kg) or saline
      (0.9%) on postnatal days 3 and 5. Locomotor sensitization was then examined in
      the adult rats (postnatal day 70). Animals were injected with quinpirole
      (0.5mg/kg, s.c.) or saline every other day for a total of 10 injections and
      locomotor activity was assessed for 60min immediately following injections 1, 2,
      4, 6, and 10. Animals also received a 'challenge' injection of 0.5mg/kg
      quinpirole 28 days after injection 10, to assess persistence of behavioural
      sensitization. Locomotor activity progressively increased with repeated
      administration of quinpirole, indicating locomotor sensitization in all of the
      drug-treated groups. There was an overall sex difference, with females showing
      significantly greater sensitization than males. Moreover, neonatal LPS treatment
      potentiated both the level and the rate of development of locomotor sensitization
      to quinpirole administration in females, but not in males. Thus, the current
      study revealed that neonatal exposure to bacterial infection increases dopamine
      (D(2)/D(3)) agonist sensitivity in a sex-specific manner. These findings have
      important implications for the sexually dimorphic development of addictions to
      both natural and artificial rewards.

PMID- 17449224
TI  - The NOD allele of the Idd5 locus on chromosome 1 mediates a non-cell-autonomous
      defect in negative selection of T cells.
AB  - Recent data have suggested that non-obese diabetic (NOD) mice display a defect in
      negative thymic selection. Using mixed bone marrow chimeras, we demonstrate that
      the NOD allele of the diabetes susceptibility region 5 (Idd5) locus on chromosome
      1, confers defective negative selection in response to endogenous superantigens
      (SAg) Mtv8 and Mtv9. We generated mixed bone marrow (BM) chimeras in which the
      donor cells of NOD and C3H or NOD.Idd5(b10) and C3H coexist and are similarly
      exposed to the Mtv8 and Mtv9 SAg. Under these conditions, SAg-mediated deletion
      of Vbeta11+ T cells is less efficient in chimeric mice reconstituted with NOD+C3H
      BM, compared with chimeras reconstituted with NOD.Idd5(b10)+C3H BM.
      Interestingly, the observed discrepancy was not T cell autonomous but was found
      to be mediated by a BM derived cellular subset, and under control of a gene(s) in
      the Idd5 region.

PMID- 17449225
TI  - The influence of cyclosporin A on lymphocyte attenuator expression.
AB  - B and T lymphocyte attenuator (BTLA), a recently identified immune inhibitory
      receptor, has been demonstrated to have the ability to maintain self-tolerance
      and transplant-tolerance in mice. However, little is known about the effects of
      immunosuppressive drugs on the expression of BTLA. In the present study, we
      observed that the immunosuppressive drug cyclosporin A (CsA) could significantly
      reduce BTLA but not CD25 and CD69 expression on CD4+ T cells during activation in
      vitro, while rapamycin (RPM) had little effect on it. Exogenous interleukin-2 (IL
      2) failed to reverse the inhibitory effect that CsA had on BTLA expression.
      Furthermore, phorbol 12-myristate 13-acetate (PMA) or ionomycin alone could
      efficiently induce BTLA protein expression on CD4+ and CD8+ T cells, while CsA
      significantly suppressed BTLA expression in this system. The present data
      indicate that the regulation of BTLA expression on CD4+ T cells does not depend
      on IL-2 and T cell activation but depends on calcineurin-dependent and
      calcineurin-independent pathways. The observation that CsA significantly inhibits
      BTLA expression on CD4+ T cells during activation, suggests that CsA might block
      the immune tolerance induced by BTLA and potentially increase the susceptibility
      to autoimmune diseases and graft rejection.

PMID- 17449226
TI  - Distinct regions of Galpha13 participate in its regulatory interactions with RGS
      homology domain-containing RhoGEFs.
AB  - Galpha12 and Galpha13 transduce signals from G protein-coupled receptors to RhoA
      through RhoGEFs containing an RGS homology (RH) domain, such as p115 RhoGEF or
      leukemia-associated RhoGEF (LARG). The RH domain of p115 RhoGEF or LARG binds
      with high affinity to active forms of Galpha12 and Galpha13 and confers specific
      GTPase-activating protein (GAP) activity, with faster GAP responses detected in
      Galpha13 than in Galpha12. At the same time, Galpha13, but not Galpha12, directly
      stimulates the RhoGEF activity of p115 RhoGEF or nonphosphorylated LARG in
      reconstitution assays. In order to better understand the molecular mechanism by
      which Galpha13 regulates RhoGEF activity through interaction with RH-RhoGEFs, we
      sought to identify the region(s) of Galpha13 involved in either the GAP response
      or RhoGEF activation. For this purpose, we generated chimeras between Galpha12
      and Galpha13 subunits and characterized their biochemical activities. In both
      cell-based and reconstitution assays of RhoA activation, we found that replacing
      the carboxyl-terminal region of Galpha12 (residues 267-379) with that of Galpha13
      (residues 264-377) conferred gain-of-function to the resulting chimeric subunit,
      Galpha12C13. The inverse chimera, Galpha13C12, exhibited basal RhoA activation
      which was similar to Galpha12. In contrast to GEF assays, GAP assays showed that
      Galpha12C13 or Galpha13C12 chimeras responded to the GAP activity of p115 RhoGEF
      or LARG in a manner similar to Galpha12 or Galpha13, respectively. We conclude
      from these results that the carboxyl-terminal region of Galpha13 (residues 264
      377) is essential for its RhoGEF stimulating activity, whereas the amino-terminal
      alpha helical and switch regions of Galpha12 and Galpha13 are responsible for
      their differential GAP responses to the RH domain.

PMID- 17449227
TI  - Compositional dynamics of guanine and cytosine content in prokaryotic genomes.
AB  - Nucleotide compositional analyses of disparities in genomic guanine and cytosine
      (gGC) content directly relate to the amino acid composition, through the union of
      the genetic code. Here we analyzed 229 prokaryotic genomes to address the
      intricate relationships between gGC, amino acids and their codons in the context
      of genes. First, we not only confirmed the universal rule that the average GC
      content at codon position 1 (GC1) is always higher than that at codon position 2
      (GC2), but also extended the rule to show that it holds true even when codon
      position-related GC contents are calculated on a per gene basis. The "GC1>GC2
      rule" is attributable essentially to a few dominant amino acids that have GC at
      one of these two codon positions or the intermediate-GC group of amino acids.
      Second, we found that gGC fluctuations were largely compensated for at the codon
      level, when codons belonging to high-GC and low-GC amino acid groups varied
      accordingly. Finally, we found that prokaryotic genes also have a GC content
      gradient (Gd) distributed along their transcripts. The gradients at three codon
      positions (Gd1, Gd2 and Gd3) all correlated with gGC in two different directions:
      Gd3 was positive, whereas the other two were negative.

PMID- 17449228
TI  - Insufficient differentiation of live and dead Campylobacter jejuni and Listeria
      monocytogenes cells by ethidium monoazide (EMA) compromises EMA/real-time PCR.
AB  - Recently, ethidium monoazide (EMA) has been proposed as a means of reducing the
      real-time PCR signal originating from free DNA and dead bacterial cells by
      selectively entering damaged cells and blocking the DNA for PCR amplification via
      photoactivation. The present study investigated the effect of EMA on viable and
      dead bacterial cells using real-time PCR, plate count method and microscopy. The
      foodborne pathogens Campylobacter jejuni and Listeria monocytogenes were used as
      a Gram-negative and a Gram-positive model organism, respectively. EMA/real-time
      PCR analysis of heat-treated cultures of C. jejuni and L. monocytogenes
      containing 2.6x10(5) and 4x10(5) viable and 3x10(6) and 2x10(6) dead cells/ml,
      respectively, yielded 2x10(3) and 5.2x10(4) bacterial cell equivalents/ml after
      EMA treatment, thus underestimating the viable cell count in the samples. Similar
      results were obtained when analyzing late exponential phase cultures of C. jejuni
      and L. monocytogenes. Inhibition of growth by EMA was observed. It depended on
      the concentration of the bacterial cells present in the sample and the EMA
      concentration used (100-1 microg/ml). An EMA concentration at which dead cells
      would stain brightly and viable cells would not stain at all or would be very
      pale was not identified, as revealed by comparison with the results of a
      commercial live/dead stain. The results suggest that EMA influences not only dead
      but also viable cells of C. jejuni and L. monocytogenes. Thus EMA/real-time PCR
      is a poor indicator of cell viability.

PMID- 17449229
TI  - Cell autonomous requirement for TGF-beta signaling during odontoblast
      differentiation and dentin matrix formation.
AB  - TGF-beta subtypes are expressed in tissues derived from cranial neural crest
      cells during early mouse craniofacial development. TGF-beta signaling is critical
      for mediating epithelial-mesenchymal interactions, including those vital for
      tooth morphogenesis. However, it remains unclear how TGF-beta signaling
      contributes to the terminal differentiation of odontoblast and dentin formation
      during tooth morphogenesis. Towards this end, we generated mice with conditional
      inactivation of the Tgfbr2 gene in cranial neural crest derived cells.
      Odontoblast differentiation was substantially delayed in the Tgfbr2(fl/fl);Wnt1
      Cre mutant mice at E18.5. Following kidney capsule transplantation, Tgfbr2 mutant
      tooth germs expressed a reduced level of Col1a1 and Dspp and exhibited defects
      including decreased dentin thickness and absent dentinal tubules. In addition,
      the expression of the intermediate filament nestin was decreased in the Tgfbr2
      mutant samples. Significantly, exogenous TGF-beta2 induced nestin and Dspp
      expression in dental pulp cells in the developing tooth organ. Our data suggest
      that TGF-beta signaling controls odontoblast maturation and dentin formation
      during tooth morphogenesis.

PMID- 17449230
TI  - Nondestructive quantitative analysis of erythromycin ethylsuccinate powder drug
      via short-wave near-infrared spectroscopy combined with radial basis function
      neural networks.
AB  - A new assay method for the nondestructive determination of erythromycin
      ethylsuccinate powder drug via short-wave near-infrared spectroscopy (NIR)
      combined with radial basis function (RBF) neural networks is investigated. The
      modern near-infrared spectroscopy analysis technique is efficient, simple and
      nondestructive, which has been used in chemical analysis in diverse fields. Short
      wave NIR is a more rapid, flexible, and cost-effective method to control product
      concentration in pharmaceutical industry. The RBF neural networks are local
      approximation networks that have superiorities in function approximation and
      learning speed. In addition, the structure of RBF networks is simple. Estimate
      and calibration of the sample concentration via short-wave NIR are made with the
      aid of RBF models based on conventional spectra, standard normal variate (SNV),
      multiplicative scatter correction (MSC) and the first-derivative spectra. Various
      optimum models of them are established and compared. Experiment results show that
      the models of SNV spectra can give better performance, and the optimized RBF
      neural network model after SNV treatment were given, by which the root-mean
      square-errors (RMSE) for calibration set and test set were 0.3266% and 0.5244%,
      respectively and the correlation coefficients (R) for calibration set and test
      set were 0.9942 and 0.9852, respectively. The proposed RBF method based on short
      wave NIR is more valuable and economical for quantitative analysis than
      traditional methods such as partial least squares (PLS).

PMID- 17449231
TI  - Whole grain intake and cardiovascular disease: a meta-analysis.
AB  - BACKGROUND AND AIMS: Whole grain food sources have been associated with lowered
      risk of cardiovascular disease (CVD). Studies in recent years have strengthened
      this observation and elucidated potential mechanisms for this association. This
      study sought to quantitate the available observational evidence on whole grain
      intake and clinical cardiovascular events. METHODS AND RESULTS: Seven prospective
      cohort studies with quantitative measures of dietary whole grains and clinical
      cardiovascular outcomes were identified from MEDLINE searches and a review of the
      literature. Based on event estimates adjusted for cardiovascular risk factors,
      greater whole grain intake (pooled average 2.5 servings/d vs. 0.2 servings/d) was
      associated with a 21% lower risk of CVD events [OR 0.79 (95% CI: 0.73-0.85)].
      Similar estimates were noted for different CVD outcomes (heart disease, stroke,
      fatal CVD) and in sex-specific analyses. Conversely, refined grain intake was not
      associated with incident CVD events [1.07 (0.94-1.22)]. CONCLUSIONS: There is a
      consistent, inverse association between dietary whole grains and incident
      cardiovascular disease in epidemiological cohort studies. In light of this
      evidence, policy-makers, scientists, and clinicians should redouble efforts to
      incorporate clear messages on the beneficial effects of whole grains into public
      health and clinical practice endeavors.

PMID- 17449232
TI  - The effect of stress on markers of cardiovascular health.

PMID- 17449233
TI  - Relationship of IL-8 production and the CagA status in AGS cells infected with
      Helicobacter pylori exposed to low pH and activating transcription factor 3
      (ATF3).
AB  - We examined the kinetics of IL-8 production and CagA status in AGS infected with
      Helicobacter pylori, 26695 (Western CagA-type), HPK5 (Eastern CagA-type) and
      isogenic cagA-disrupted mutants, exposed to different pH (pH 6 and pH 3). IL-8
      was produced in the early and late phases after infection in CagA-dependent and 
      independent manners, respectively, irrespective of CagA-type. The wild-type
      exposed to low pH tremendously reduced IL-8 level at early phase, but restored
      with urea, suggesting that low pH exerted the kinetics of H. pylori-induced IL-8
      production in CagA-dependent manner and urea was necessary for effective
      induction. CagA and phosphorylated CagA increased time-dependently after
      infection. Phosphorylated CagA from 26695, but not HPK5, rapidly peaked,
      consistent with the kinetics of IL-8 induction and appearance of hummingbird
      phenotype. ATF3 transcripts peaked late phase by wild-type, however, induced in
      two peaks early and late phases by cagA-disrupted mutants, indicating that
      different CagA-type proteins altered ATF3 induction in the infected cells.

PMID- 17449234
TI  - Systemic inflammation and systemic oxidative stress in patients with acute
      exacerbations of COPD.
AB  - BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the
      inflammatory processes and oxidative stress are closely linked in the lung
      compartment. However, the relationships between systemic inflammation and
      parameters of oxidative stress in the systemic circulation during acute
      exacerbations of COPD remain to be explored. OBJECTIVE: To analyze relationships
      between erythrocytic glutathione peroxidase (GPx), a marker of systemic oxidative
      stress, and parameters reflecting systemic inflammation, such as circulating
      neutrophils, C-reactive protein (CRP), and interleukin (IL)-6, in patients with
      acute exacerbations of COPD. PATIENTS AND METHODS: We measured erythrocytic GPx
      activity, circulating neutrophil count, and serum high-sensitivity (hs) CRP and
      IL-6 in 177 patients admitted to the hospital due to an acute exacerbation of
      COPD (91 males, mean age 66.8+/-0.9 years, mean FEV1 45.3+/-1.3% predicted).
      RESULTS: From GOLD Stage II to Stage III and IV, erythrocytic GPx activity
      significantly decreased [mean+/-SEM: from 44.3+/-1.7 U/g Hb to 40.8+/-1.1 U/g Hb
      and to 38.4+/-1.5 U/g Hb, p = 0.037], while serum hsCRP increased [median (25th,
      75th percentile): from 9.6 (3.0, 23.0) mg/l to 23.3 (6.4, 46.8) mg/l, and to 26.7
      (6.5, 117.2) mg/l, p = 0.004]. Erythrocytic GPx activity was significantly
      inversely related to both, log neutrophil count (r = -0.219, p = 0.003) and log
      hsCRP (r = -0.199, p = 0.008). CONCLUSIONS: Our study suggests an association
      between systemic inflammation and systemic oxidative stress reflected by
      erythrocytic GPx in patients with acute exacerbations of COPD.

PMID- 17449235
TI  - Is there a role for test-dosing through the Tuohy needle?

PMID- 17449236
TI  - Do different endocytic pathways make different synaptic vesicles?
AB  - At a wide range of synapses, synaptic vesicles reside in distinct pools that
      respond to different stimuli. The recycling pool supplies the vesicles required
      for release in response to modest stimulation, whereas the reserve pool is
      mobilized only by strong stimulation. Multiple pathways have been proposed for
      the recycling of synaptic vesicles after exocytosis, but the relationship of
      these pathways to the different synaptic vesicle pools has remained unclear.
      Synaptic vesicle proteins have also been assumed to undergo recycling as a unit.
      However, emerging data indicate that differences in the association with distinct
      endocytic adaptors such as the heterotetrameric adaptor AP3 influence the
      trafficking of individual synaptic vesicle proteins, affecting the composition of
      synaptic vesicles and hence their functional characteristics. These observations
      might begin to account for differences in the properties of different vesicle
      pools.

PMID- 17449237
TI  - Analysis of 11q22-q23 deletion target genes in B-cell chronic lymphocytic
      leukaemia: evidence for a pathogenic role of NPAT, CUL5, and PPP2R1B.
AB  - Deletion of 11q22-q23 is associated with an aggressive course of B-cell chronic
      lymphocytic leukaemia (B-CLL). Since only in a subset of these cases biallelic
      inactivation of ATM was observed, we sought to identify other disease-associated
      genes within 11q22-q23 by analysing NPAT (cell-cycle regulation), CUL5 (ubiquitin
      dependent apoptosis regulation) and PPP2R1B (component of the cell-cycle and
      apoptosis regulating PP2A) for point mutations and their expression in B-CLL by
      single-strand conformation polymorphism/sequence analysis of the transcripts and
      real-time polymerase chain reaction. Though none of the genes were affected by
      deleterious mutations, we observed a significant down-regulation of NPAT in B-CLL
      versus CD19+ B cells and of CUL5 in 11q deletion versus non-deletion B-CLL
      samples and measured reduced PPP2R1B transcript levels in a subset of B-CLL
      cases. Alternative splicing of PPP2R1B transcripts (skipping of exons 2/3, 3, 9)
      was associated with a reduced activity of protein phosphatase 2A. Together, these
      results implicate deregulation of the cell-cycle and apoptosis regulators NPAT,
      CUL5 and PPP2R1B and a role for these genes in the pathogenesis of B-CLL.

PMID- 17449238
TI  - Novel challenges in exploring peptide ligands and corresponding tissue-specific
      endothelial receptors.
AB  - The structural and molecular diversity of vascular endothelium may depend on the
      functional state and tissue localisation of its cells. Tumour vasculature
      expresses a number of molecular markers that distinguish it from normal
      vasculature. In cancer, the determinant of specific tumour vasculature
      heterogeneity is, in part, dictated by dysregulated expression of tumour-derived
      angiogenic factors. The identification of molecular 'addresses' on the surface of
      tumour vasculature has significantly contributed to the selection of targets,
      which have been used for delivering therapeutic and imaging agents in cancer.
      Cytotoxic drug, pro-apoptotic peptides, protease inhibitors, and gene therapy
      vectors have been successfully linked to peptides and delivered to tumour sites
      with an improved experimental therapy. Different diagnostic and therapeutic
      compounds can be efficiently targeted to specific receptors on vascular
      endothelial cells; the development of ligand-directed vector tools may promote
      systemic targeted gene delivery. Here, we review the very recent advances in the
      identification of peptide ligands and their corresponding tissue-specific
      endothelial receptors through the phage display technology with emphasis on
      ligand-directed delivery of therapeutic agents and targeted gene therapy.

PMID- 17449240
TI  - Sequence analysis of retinoic acid receptor alpha, beta and gamma isoforms in the
      lizard, Podarcis sicula.
AB  - Vitamin A and its principal biologically active derivative, retinoic acid (RA),
      play a fundamental role in diverse processes, such as proliferation,
      differentiation, morphogenesis, metabolism and apoptosis of many types of cells.
      In addition, RA has been shown to be involved in the regulation of testicular
      function. These effects are mediated by interaction with two families of nuclear
      receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR), each with
      three subtypes alpha, beta and gamma. The physiological involvement of retinoids
      in testicular function has been conducted mainly in mammals. Recently, we found
      that exogenous all-trans-retinoic acid impairs spermatogenesis and enhance
      testicular germ cell apoptosis in the lizard, Podarcis sicula, a seasonal
      breeder. To further investigate the role of retinoic acid in lizard, we focus
      this work principally on the characterization of lizard retinoic acid receptors
      (alpha, beta and gamma isoforms). RARalpha is 2720 bp long with a putative ORF
      between 699 and 2133. A Kozac sequence is present at 696 and a putative poly
      adenilation site is present in position 2612. The RARalpha sequence shares 87%
      homology with mouse RARalpha mRNA while it has 76 and 80% homology with lizard
      RARbeta and gamma mRNAs. RARbeta is 2478 bp long showing a putative ORF between
      196 and 1543. A canonical Kozac sequence is present at 193 and a putative poly
      adenilation site is present at 2294. RARbeta shares 91% homology with mouse
      RARbeta mRNA and has 76% homology with both RARalpha and gamma. RARgamma is
      2416bp long. With a putative ORF between 444 and 1818. A Kozac sequence is
      present at 441 and a putative poly-adenilation site is present at 2288. RARgamma
      shares 86% homology with mouse RARbeta mRNA and has 80 and 76% homology with both
      RARalpha and beta respectively. It is worth to note that, as in mouse, the 5'UTR
      of all isoforms is TATA and CAAT less. Both Northern blot and PCR analyses
      indicate that lizard testis expresses only RARalpha and RARbeta mRNAs, while
      RARgamma mRNA transcript was not found. In the period analysed, RARbeta was
      expressed during the gonadal full activity (May) and RARalpha was present in the
      post-reproductive period (August). During the autumnal recrudescence (October)
      RARalpha and RARbeta are co-expressed and, as indicated by quantitative PCR
      analysis, RARbeta mRNA levels are lower than RARalpha ones. Thus, the appearance
      and abundance of each receptor correspond to a specific phase of lizard
      reproductive cycle, allow us to hypothesize that each RAR subtype could play a
      specific role in the regulation of spermatogenetic activity. The results of the
      present study show, for the first time, the characterization of RAR mRNAs in the
      testis of lizard P. sicula, whose expression is related to the different phase of
      reproductive cycle. Moreover, the gamma form, is principally expressed in the
      skin during the March-July period, having probably a role in regulating skin
      homeostasis and colour livery, which are important factor in mating during the
      reproductive cycle.

PMID- 17449239
TI  - Cell lines from MYCN transgenic murine tumours reflect the molecular and
      biological characteristics of human neuroblastoma.
AB  - Overexpression of the human MYCN oncogene driven by a tyrosine hydroxylase
      promoter causes tumours in transgenic mice that recapitulate the childhood cancer
      neuroblastoma. To establish an in vitro model to study this process, a series of
      isogenic cell lines were developed from these MYCN-driven murine tumours. Lines
      were established from tumours arising in homozygous and hemizygous MYCN
      transgenic mice. Hemizygous tumours gave rise to cell lines growing only in
      suspension. Homozygous tumours gave rise to similar suspension lines as well as
      morphologically distinct substrate-adherent lines characteristic of human S-type
      neuroblastoma cells. FISH analysis demonstrated selective MYCN transgene
      amplification in cell lines derived from hemizygous mice. Comparative genomic
      hybridisation (CGH) and fluorescence in situ hybridisation (FISH) analysis
      confirmed a range of neuroblastoma-associated genetic changes in the various
      lines, in particular, gain of regions syntenic with human 17q. These isogenic
      lines together with the transgenic mice thus represent valuable models for
      investigating the biological characteristics of aggressive neuroblastoma.

PMID- 17449241
TI  - Anaerobic treatment of a chemical synthesis-based pharmaceutical wastewater in a
      hybrid upflow anaerobic sludge blanket reactor.
AB  - In this study, performance of a lab-scale hybrid up-flow anaerobic sludge blanket
      (UASB) reactor, treating a chemical synthesis-based pharmaceutical wastewater,
      was evaluated under different operating conditions. This study consisted of two
      experimental stages: first, acclimation to the pharmaceutical wastewater and
      second, determination of maximum loading capacity of the hybrid UASB reactor.
      Initially, the carbon source in the reactor feed came entirely from glucose,
      applied at an organic loading rate (OLR) 1 kg COD/m(3) d. The OLR was gradually
      step increased to 3 kg COD/m(3) d at which point the feed to the hybrid UASB
      reactor was progressively modified by introducing the pharmaceutical wastewater
      in blends with glucose, so that the wastewater contributed approximately 10%,
      30%, 70%, and ultimately, 100% of the carbon (COD) to be treated. At the
      acclimation OLR of 3 kg COD/m(3) d the hydraulic retention time (HRT) was 2 days.
      During this period of feed modification, the COD removal efficiencies of the
      anaerobic reactor were 99%, 96%, 91% and 85%, and specific methanogenic
      activities (SMA) were measured as 240, 230, 205 and 231 ml CH(4)/g TVS d,
      respectively. Following the acclimation period, the hybrid UASB reactor was fed
      with 100% (w/v) pharmaceutical wastewater up to an OLR of 9 kg COD/m(3) d in
      order to determine the maximum loading capacity achievable before reactor
      failure. At this OLR, the COD removal efficiency was 28%, and the SMA was
      measured as 170 ml CH(4)/g TVS d. The hybrid UASB reactor was found to be far
      more effective at an OLR of 8 kg COD/m(3) d with a COD removal efficiency of 72%.
      At this point, SMA value was 200 ml CH(4)/g TVS d. It was concluded that the
      hybrid UASB reactor could be a suitable alternative for the treatment of chemical
      synthesis-based pharmaceutical wastewater.

PMID- 17449242
TI  - The effects of fly ash incorporation on some available nutrient contents of
      wastewater sludges.
AB  - Lignite fly ash was used as an additive in three different alkaline stabilisation
      processes and the effects on some chemical properties of wastewater sludge were
      investigated. The results of the study indicated that sludges added with fly ash
      only in a dose of 40% (on a dry weight basis) generally caused no significant
      differences in the sludge properties. However, ammonium-nitrate nitrogen,
      available phosphorus and soluble boron concentrations were slightly reduced in
      sludges which were added with 80% and 120% fly ash. On the other hand, alkaline
      stabilisation (10-15% quicklime+40-120% fly ash) and alkaline pasteurisation (10
      15% quicklime+40-120% fly ash+heating at 70 degrees C for 30 min) processes
      caused a significant decrease in available forms of nitrogen and phosphorus and a
      significant increase in pH. Although a strong relationship between fly ash dosage
      and available nitrogen concentration was obtained in alkaline stabilisation
      process, no significant correlation was found between the two parameters in
      alkaline pasteurisation process. The results also suggested that using fly ash
      with doses of 40%, 80% and 120% in alkaline pasteurisation process caused no
      significant alteration in sludge properties. Heating and quicklime addition were
      expected to be the influential factors.

PMID- 17449243
TI  - Surface topography of kenaf (Hibiscus cannabinus) sized papers.
AB  - Bleached kenaf handsheets sized with different polymers such as chitosan,
      polyvinyl alcohol and cationic starch, were used for the determination of surface
      topography. A non-contact profilometer, the AltiSur 500, was used to characterize
      the topography of structural details in the paper surface. Numerical and visual
      characterization of surface roughness indicated that the surface of chitosan
      sized paper was less rough than other surfaces, and all the sized papers were
      commonly smoother than the unsized paper. One property of bio-polymer of chitosan
      is its ability to form films that improve the surface properties of paper when it
      is applied to the surface of the sheet.

PMID- 17449244
TI  - Pyridine biodegradation in a novel rotating rope bioreactor.
AB  - A novel immobilised bioreactor has been developed especially for the treatment of
      pollutants characterized by high volatility along with high water solubility and
      low microbial yields. The new bioreactor referred to as the rotating rope
      bioreactor (RRB) provides higher interfacial area (per unit reactor liquid
      volume) along with high oxygen mass transfer rate, greater microbial culture
      stability; and consequently higher substrate loadings and removal rates in
      comparison to other conventional rectors for the treatment of volatile compounds.
      Pyridine was used as a model compound to demonstrate the enhanced performance
      with RRB, when compared to that reported with other conventional bioreactors. The
      experimental results indicate that the novel RRB system is able to degrade
      pyridine with removal efficiency of more than 85% at higher pyridine
      concentration (up to 1000 mg/l) and loading [up to 400 mg/m(2)/h (66.86
      g/m(3)/h)], with a shorter hydraulic retention time (9-18 h). The reactor has
      been in operation for the past 15 months and no loss of activity has been
      observed.

PMID- 17449245
TI  - Doubling the organic loading rate in the co-digestion of energy crops and manure-
      a full scale case study.
AB  - In the present study the increase of the organic loading rate from 2.11 to 4.25
      kg VS m(-3) d(-1) in a two stage, agricultural biogas plant was investigated. The
      process enhancement resulted in the doubling of the plant capacity from 500 kW to
      1000 kW retaining the same digester volume. Efficiency criteria showed good
      performance throughout the study. At the end of the monitoring, biogas yield was
      on the same level as before the enhancement, while volume related biogas
      productivity almost doubled from 1.50 to 2.91 Nm(3) m(-3) d(-1). However, as a
      consequence of the higher transfer of poorly degraded organic material into the
      effluent, the residual methane potential of the effluent multiplied by the factor
      10. The results of this study show, that most agricultural biogas plants in
      Austria have a great potential for a significant capacity increase. However, to
      avoid atmospheric emissions, the effluent storage of high loaded processes has to
      be integrated into the gas-tight system of the digesters.

PMID- 17449246
TI  - Technetium-99m-labeling and synthesis of thymidine analogs: potential candidates
      for tumor imaging.
AB  - The technetium-99m-labeling and synthesis of a series of thymidine analogs were
      studied. The target molecules were obtained by using 6-hydrazinopyridine-3
      carboxylic acid (HYNIC) as a bifunctional coupling agent and using N-(2-hydroxy
      1,1-bis(hydroxymethyl)ethyl)glycine (tricine) and ethylenediamine-N,N'-diacetic
      acid (EDDA) as coligands. The effects of different spacers between thymidine
      analog with HYNIC on radiochemical yield were also studied.

PMID- 17449247
TI  - Synthesis and cytotoxic activity of trisubstituted-1,3,5-triazines.
AB  - 1,3,5-Triazine derivatives were screened for phototoxicity as well as the
      cytotoxic activities against leukemia and adenocarcinoma derived cell lines in
      comparison to the normal human keratinocytes. A simple and environmentally
      friendly procedure has been developed for the synthesis of 1,3,5-triazine
      derivatives under microwave irradiation in the presence of a HY zeolite. The
      catalyst can be recovered and reused. Thus, the procedure provides a simple and
      green synthetic methodology under environmentally friendly conditions. Structure
      activity relationships between the chemical structures and antimycobacterial and
      photosynthesis-inhibiting activity of the evaluated compounds are also discussed.

PMID- 17449248
TI  - Structure-activity relationship, kinetic mechanism, and selectivity for a new
      class of ubiquitin C-terminal hydrolase-L1 (UCH-L1) inhibitors.
AB  - 3-Amino-2-keto-7H-thieno[2,3-b]pyridin-6-one derivatives were discovered as
      moderately potent inhibitors of ubiquitin C-terminal hydrolase-L1 (UCH-L1)
      utilizing an assay that measures hydrolysis of the fluorogenic substrate Ub-AMC.
      SAR studies revealed that both the carboxylate at the 5-position and the 6
      pyridone ring were critical for inhibitory activity. Furthermore, activity was
      dependent on the nature of the ketone substituent at the 2-position, with 4-Me-Ph
      and 2-naphthyl being best. Kinetic mechanism studies revealed that these
      compounds were uncompetitive inhibitors of UCH-L1, binding only to the Michaelis
      complex and not to free enzyme. The active compounds were selective for UCH-L1,
      exhibiting neither inhibition of other cysteine hydrolases (e.g., UCH-L3, papain,
      isopeptidase T, caspase-3, and tissue transglutaminase) nor cytotoxicity in N2A
      cells.

PMID- 17449249
TI  - Patients' knowledge and experience of adjuvant endocrine therapy for early breast
      cancer: a European study.
AB  - Little is known about patients' experience of, and knowledge about adjuvant
      endocrine therapy. A European survey was carried out to explore this knowledge
      gap. The 547 post-menopausal women with early breast cancer, from 9 European
      countries, completed a questionnaire about their experience and knowledge of
      their therapy. Forty one percent of women surveyed were not at all involved in
      the decision to start adjuvant endocrine therapy and only 10% were fully
      involved. Only 57% received information about possible side effects, 26% about
      the risk of their cancer returning and 15% about the possible long term effects
      of treatment. Older women, less educated women or those without Internet access
      were less likely to receive information or be involved in decision making.
      Women's right to information and involvement in decision making are not
      respected. Greater efforts are required to ensure that all patients understand
      how different therapies work so that they can make informed decisions.

PMID- 17449250
TI  - The erbB2+ cluster of the intrinsic gene set predicts tumor response of breast
      cancer patients receiving neoadjuvant chemotherapy with docetaxel, doxorubicin
      and cyclophosphamide within the GEPARTRIO trial.
AB  - Gene expression profiling using Affymetrix HG-U133 Arrays (22,500 genes) was
      performed on fresh frozen pretherapeutic core biopsies from 50 patients
      undergoing neoadjuvant chemotherapy (NAC) with docetaxel, adriamycin,
      cyclophosphamide (TAC) within the GEPARTRIO trial. The Sorlie classification
      based on the "intrinsic gene set" revealed four different subgroups in our cohort
      (normal-like: 14%, basal-like: 20%, erbB2+: 22% and luminal: 44%), which is in
      line with the original description. High genomic grade but not histopathological
      grading was statistically different within the four subgroups (P<0.001). About
      45.5% of tumors classified according to erbB2+ cluster showed a pathological
      complete response compared to 0% in the normal-like, 10.0% in the basal-like and
      9.1% in the luminal subgroup (P=0.024). There was a trend to less tumor relapses
      in the erbB2+ subgroup (0%) compared to the normal-like (28.6%), basal-like
      (30.0%) and luminal (13.6%) cluster (P=0.215). Our data suggest that the
      molecular tumor subtypes based on the "intrinsic gene set" can be used to predict
      tumor response according to NAC.

PMID- 17449251
TI  - Intensive and critical care nursing.

PMID- 17449252
TI  - The meaning of posttraumatic stress-reactions following critical illness or
      injury and intensive care treatment.
AB  - Traumatic events connected with a critical condition and treatment in the
      intensive care unit (ICU) may result in subsequent posttraumatic stress
      reactions. The aim of this phenomenological study was to describe the meaning of
      posttraumatic stress-reactions as experienced by individuals following a critical
      illness or injury and intensive care. Fourteen informants, testing positive for
      posttraumatic stress-reactions as a clinical concern, were interviewed. The data
      was analysed following the principles indicated by Giorgi [Giorgi A. The theory,
      practice, and evaluation of the phenomenological method as a qualitative research
      procedure. J Phenomenol Psychol 1997;28:235-61]. The essence of the phenomenon of
      posttraumatic stress-reactions was understood as a transition to a life-situation
      beyond control, where the traumatic experiences have a profound impact and are
      ever-present. The variations of the phenomenon presented themselves as a need to
      make sense of the traumatic memories, which live on; being haunted by the trauma;
      a need to escape; distress and strain in the life-situation; transformation of
      self and, finally, interactions with others affected. The need for caring
      strategies and support is emphasised, both in the ICU and afterwards, thus
      preventing or alleviating some of the suffering.

PMID- 17449253
TI  - Evaluation of a diverse set of potential P1 carboxylic acid bioisosteres in
      hepatitis C virus NS3 protease inhibitors.
AB  - There is an urgent need for more efficient therapies for people infected with
      hepatitis C virus (HCV). HCV NS3 protease inhibitors have shown proof-of-concept
      in clinical trials, which make the virally encoded NS3 protease an attractive
      drug target. Product-based NS3 protease inhibitors comprising a P1 C-terminal
      carboxylic acid have shown to be effective and we were interested in finding
      alternatives to this crucial carboxylic acid group. Thus, a series of diverse P1
      functional groups with different acidity and with possibilities to form a
      similar, or an even more powerful, hydrogen bond network as compared to the
      carboxylic acid were synthesized and incorporated into potential inhibitors of
      the NS3 protease. Biochemical evaluation of the inhibitors was performed in both
      enzyme and cell-based assays. Several non-acidic C-terminal groups, such as
      amides and hydrazides, were evaluated but failed to produce inhibitors more
      potent than the corresponding carboxylic acid inhibitor. The tetrazole moiety,
      although of similar acidity to a carboxylic acid, provided an inhibitor with
      mediocre potencies in both assays. However, the acyl cyanamide and the acyl
      sulfinamide groups rendered compounds with low nanomolar inhibitory potencies and
      were more potent than the corresponding carboxylic acid inhibitor in the
      enzymatic assay. Additionally, results from a pH-study suggest that the P(1) C
      terminal of the inhibitors comprising a carboxylic acid, an acyl sulfonamide or
      an acyl cyanamide group binds in a similar mode in the active site of the NS3
      protease.

PMID- 17449254
TI  - Radioiodination of new EGFR inhibitors as potential SPECT agents for molecular
      imaging of breast cancer.
AB  - In our search for the development of novel SPECT radioligands for EGFR positive
      tumours, new potentially irreversible tyrosine kinase (TK) inhibitors are being
      explored. The radioiodination of N-{4-[(3-chloro-4-fluorophenyl)
      amino]quinazoline-6-yl}-3-bromopropionamide, a novel EGFR-TK inhibitor
      synthesised in our laboratory, was accomplished via halogen exchange.
      Purification by RP-HPLC gave [125I]-N-{4-[(3-chloro-4
      fluorophenyl)amino]quinazoline-6-yl}-3-iodopropionamide with a radiochemical
      purity higher than 95% and a high specific activity. In vitro studies indicate
      that both iodinated quinazoline and its bromo precursor inhibit A431 cell growth
      and also possess higher potency than the parent quinazoline to inhibit the EGFR
      autophosphorylation. In vivo stability studies suggest metabolization of the
      radioiodinated quinazoline indicating a short biological half-life. The in vitro
      results point out that these quinazoline derivatives could be promising
      candidates for SPECT imaging of EGFR positive tumours provided that they are
      selectively modified in order to achieve better in vivo radiochemical stability.

PMID- 17449255
TI  - Explaining cyclodextrin-mycotoxin interactions using a 'natural' force field.
AB  - Docking techniques and the HINT (Hydropathic Interaction) program were used to
      explain interactions of aflatoxin B(1) and ochratoxin A with beta- and gamma
      cyclodextrins. The work was aimed at designing a chemosensor to identify very low
      concentrations of these mycotoxins by exploiting the affinity of the cyclodextrin
      cavity for many small organic molecules. Actually, the inclusion of the
      fluorescent portion of these toxins into the cavity may lower the quenching
      effect of the solvent, thus enhancing the luminescence. HINT is a 'natural' force
      field, based on experimentally determined LogP(octanol/water) values, that is
      able to consider both enthalpic and entropic contributions to the binding free
      energy with an unified approach. HINT is normally applied to predict the DeltaG
      degrees of binding for protein-ligand, protein-protein, and protein-DNA
      interactions. The leading forces in biomolecular processes are the same as those
      involved in organic host-guest inclusion phenomena, therefore we applied this
      methodology for the first time to cyclodextrin complexes. The results allowed us
      to explain spectroscopic data in absence of available crystallographic or NMR
      structural data.

PMID- 17449256
TI  - Comparison for quality assurance of (99m)Tc activity measurements with
      radionuclide calibrators.
AB  - In 2005, the Physikalisch-Technische Bundesanstalt (PTB) and the QSA Global GmbH
      (QSA) organised a national comparison of (99m)Tc solution measurements. The
      purpose of this comparison was to gain information on the quality of routine
      activity measurements carried out in the field of nuclear medicine in Germany. In
      addition to this, an ampoule containing a calibrated (99m)Tc solution was sent
      from PTB to the Bureau International des Poids et Mesures (BIPM) to have the
      activity result entered into the database of the International Reference System
      (SIR), and thus demonstrating traceability of the measurements to the SI. In the
      following, we will report on the activity standardisation carried out at the PTB,
      and on the way in which the national comparison had been organised, and we will
      provide information on the analysis as well as on its results.

PMID- 17449257
TI  - Temporal and spatial expression of osteoprotegerin and receptor activator of
      nuclear factor -kappaB ligand during mandibular distraction in rats.
AB  - PURPOSE: The expression profiles of osteoprotegerin and receptor activator of
      nuclear factor-kappaB ligand (RANKL) were investigated in the distraction region
      to reveal bone remodelling characters during mandibular distraction osteogenesis.
      MATERIAL AND METHODS: Osteotomies were performed and external distractors were
      used on the mandibles of 42 adult male SD rats. After a 5-day latency period, the
      distractors were activated at a rate of 0.4mm/day for 6 days, followed by a 4
      week consolidation period. Radiographs were taken, and specimens were harvested
      at the end of the latency period, when distraction was completed, and at the end
      of 1, 2, 3 and 4 weeks of the consolidation period. Tartrate-resistant acid
      phosphatase staining was used to detect activated osteoclasts. Temporospatial
      expression of osteoprotegerin and RANKL was investigated by using
      immunohistochemistry, in situ hybridization and reverse transcription polymerase
      chain reaction. Semi-quantitative analysis was used to characterize
      osteoprotegerin (OPG). RANKL and RANKL/OPG ratio. RESULTS: In all time points,
      osteoprotegerin and RANKL were co-localized in bone marrow lining cells,
      osteoblasts and newly embedded osteocytes. Osteoprotegerin mRNA expression
      increased to a peak when distraction was completed and maintained this level
      until the end of week 2 of the consolidation period. RANKL mRNA expression
      increased steadily until the end of week 1 of the consolidation period and
      maintained a peak level until the end of week 3, with a slight decrease at the
      end of week 2. The RANKL/OPG ratio increased continuously and reached its highest
      level at the end of weeks 3 and 4 of the consolidation period. Tartrate-resistant
      acid phosphatase staining positive osteoclasts were mainly detected at weeks 2, 3
      and 4 of the consolidation period in bone marrow cavities and bone surfaces.
      CONCLUSIONS: The temporospatial expression patterns of osteoprotegerin and RANKL
      suggest that the osteoblast lineage cell network orchestrates bone remodelling
      during distraction osteogenesis and most activated bone resorption takes place
      during weeks 3 and 4 of the consolidation phase.

PMID- 17449258
TI  - Head and neck cancer, treatment, evolution and post therapeutic survival - Part
      2: a decade's results 1993-2002.
AB  - INTRODUCTION AND OBJECTIVES: In the second part of an analysis of a 10-year
      period of treating oral cancer patients, the focus was the efficiency of
      treatment, recurrence rates and survival. PATIENTS AND METHODS: From 1485
      patients with oral and maxillofacial malignant tumours, 1072 cases could be
      evaluated. The following data were analyzed statistically: patients' charts and
      medical records including the follow-up reports. RESULTS: From all patients
      studied, 811 underwent surgical treatment alone, the mean recurrence rate was
      23%. The recurrence rate after surgery plus radiotherapy was 38%; after surgical
      treatment alone it was 23%; the survival rate at 3 and 5 years post
      therapeutically was 49% and 31%, respectively. CONCLUSIONS: The first choice
      therapy for carcinomas is surgical. The recurrence rate increased with lymph node
      involvement and tumour size.

PMID- 17449259
TI  - Head and neck cancer, epidemiology and histological aspects - Part 1: a decade's
      results 1993-2002.
AB  - INTRODUCTION AND OBJECTIVES: Studies prior to 1990 showed an incidence of 5% for
      oral and maxillofacial cancer in Romania. In this paper (Part 1) an evaluation of
      malignant tumour cases, covering a 10-year period is made regarding histological
      forms, the relationships of malignant tumours to patients' geographic origin,
      environment, age, gender of patients and lymph node involvement. PATIENTS AND
      METHODS: From 1485 patients with malignant oral and maxillofacial tumours, 1072
      cases fulfilled the criteria for inclusion in this study. The following data were
      examined: patients' charts and medical records as well as pathology reports.
      RESULTS: From 16,315 patients admitted to this hospital between 1993 and 2002, 9%
      presented with primary ('de novo') malignant tumours; 2/3 were male patients;
      average age at presentation was 61 years for males and 59 years for females; 47%
      presented with stage IV tumours; out of the 'de novo' tumours, 93% were
      carcinomas and 4% sarcomas; 56% of patients had positive lymph nodes at
      presentation. CONCLUSIONS: The number of head and neck cancer cases increased in
      the last 15 years; almost half of the patients presented with tumours in stage
      IV.

PMID- 17449260
TI  - A lingual osteoid mass originating from hyaline cartilage.
AB  - BACKGROUND: Lingual osseous and chondromatous growths are rare but well-defined
      entities. The cause of these growths is still unknown, but several theories have
      been proposed. CASE PRESENTATION: A mass measuring one cm in diameter on the
      dorsum of the tongue in a 28-year-old male causing discomfort was found to
      consist predominantly of hyaline cartilage with prominent bone transformation.
      CONCLUSION: This finding confirms that bony masses in the tongue may originate
      from cartilaginous precursors, in contrast to similar masses seen on the face
      which are (often) purely osseous.

PMID- 17449261
TI  - Atypical midline cleft with duplication of the metopic suture.
AB  - INTRODUCTION: In contrast to the common clefts of the lip, alveolus and palate,
      the atypical clefts of the face may come in myriad patterns of clinical
      expression and are often not easy to define. PURPOSE: In this report, a case of
      median craniofacial dysraphia is described. PATIENT: At presentation, the 3-month
      old male patient had a bilateral complete cleft of the lip, alveolus and palate.
      The nose was wide and a horn was present on the nasal dorsum. 3-D CT AND MRI
      REVEALED: Duplication of the metopic suture ending at the wide anterior fontanel;
      orbital hypertelorism; midline cranial cleft ending just superior to the nasal
      dorsum; frontoethmoidal encephalocoele and holoprosencephaly. The presence of two
      metopic sutures was confirmed during surgery. CONCLUSION: The presented case
      carries the characteristics of the median cleft face syndrome. However, it
      differs from similar cases in two respects. First, the patient had two metopic
      sutures, one on either side of the cranial extension of the median cleft. Second,
      the patient had a bilateral cleft lip in contrast to the expected median cleft
      lip deformity.

PMID- 17449262
TI  - Being an elderly woman: is it a risk factor for morbidity after coronary artery
      bypass surgery?
AB  - OBJECTIVE: Despite the refinements in surgical techniques and postoperative care,
      elderly women still have a higher prevalence of postoperative morbidity. METHODS:
      The outcomes of 112 elderly women (>80 years) who underwent an elective CABG
      procedure were compared with those of males operated during the same time
      interval (n, 164). RESULTS: Median age of female and male patients were 82 and 83
      years, respectively. Mean number of grafts did not differ significantly (3.7+/
      0.8 vs 3.9+/-0.3, p=0.4) between groups. Overall early operative mortality rate
      was 8.6% (24 of 276 patients); 8.9% (10 of 112 patients) for female and 8.5% (14
      of 164 patients) for male patients (p=0.1). Postoperative complications including
      prolonged ventilation time (13.4% in females vs 8.5% in male, p<0.01), atrial
      fibrillation (40% in females vs 33% in males, p=0.01), sternal reclosure (8% in
      females vs 4.2% in males, p=0.01), pneumonia (5.3% in females vs 3% in males,
      p=0.03), leg wound infection (11.7% in females vs 2.4% in males, p<0.001), renal
      dysfunction (10.7% in females vs 7.3% in young patients, p=0.02) have been found
      to be significantly higher in elderly women. Mean intensive care unit (3.2+/-1.1
      days in females vs 1.6+/-0.4 in males, p=0.03), and hospital stays (13.6+/-2.1
      days in females vs 9.1+/-1.2 in males, p=0.02) were also longer in female
      patients. Five-year survivals including all deaths for female and male patients
      were 57% and 62%, respectively. CONCLUSIONS: In elderly women, revascularization
      procedures can be done with acceptable mortality rates; but these patients are
      still associated with a higher prevalence of postoperative morbidity when
      compared with the male counterparts. Therefore, these patients have to be very
      carefully evaluated preoperatively and their postoperative care should be more
      comprehensive to reduce the incidence of postoperative complications.

PMID- 17449263
TI  - Does patch closure of subarterial ventricular septal defect affect the growth of
      pulmonary valve?
AB  - OBJECTIVE: Patch closure of the subarterial ventricular septal defect requires
      suture placement at the pulmonary annulus. We aimed to identify whether patch
      closure of subarterial ventricular septal defect would affect the growth of
      pulmonary annulus in comparison with that of perimembranous ventricular septal
      defect. METHODS: Of 361 patients who underwent patch closure of ventricular
      septal defect from January 1992 to December 1999, 98 (51 subarterial, 47
      perimembranous) had echocardiographic data available for measurement of both
      preoperative and postoperative (more than 5 years after operation) pulmonary and
      aortic annular diameters. The pulmonary/aortic annular diameter ratio and their
      growth rates in the subarterial group were compared with those in the
      perimembranous group. The perioperative variables correlated with the pulmonary
      annular growth in subarterial group were also identified. RESULTS: The mean
      follow-up duration was 7.2 years. Preoperative pulmonary/aortic annular diameter
      ratio was 1.45 (range, 0.94-2.31) in the subarterial group and 1.57 (range, 1.15
      2.51) in the perimembranous group (p=0.059). The latest postoperative ratio was
      significantly lower in the subarterial group [subarterial: 1.02 (range, 0.77
      1.41) vs perimembranous: 1.36 (range, 1.11-1.75), p<0.01]. Twenty-three patients
      (45%) in the subarterial group had the ratio less than 1. The pulmonary annular
      growth rate in the subarterial group was lower than that in the perimembranous
      group (subarterial: 0.34 mm/year, perimembranous: 1.03 mm/year, p<0.01).
      Preoperative pulmonary/aortic annular diameter ratio (r=0.885, p<0.01), age at
      operation (r=-0417, p<0.01), weight at operation (r=-0.357, p<0.05), and
      ventricular septal defect size (r=0.298, p<0.05) were found to have correlation
      with pulmonary annular growth in the subarterial group. CONCLUSIONS: Our data
      show that pulmonary annular growth after patch repair of subarterial ventricular
      septal defect is suboptimal compared with perimembranous ventricular septal
      defect. Careful attention must be paid to the possible late clinical implication
      caused by impaired pulmonary annular growth after patch repair of subarterial
      ventricular septal defect.

PMID- 17449264
TI  - Antiplatelet therapy early after bioprosthetic aortic valve replacement is
      unnecessary in patients without thromboembolic risk factors.
AB  - BACKGROUND: The use of antithrombotic therapy during the postoperative period
      after biological aortic valve replacement (AVR) in patients without
      thromboembolic risk factors remains controversial. Treatment with warfarin is
      recommended for the first 3 months after biological AVR. The use of antiplatelet
      therapy - mainly aspirin (ASA) - is suggested as an alternative treatment but its
      efficacy is still unsettled. Due to the increased risk of bleeding complications
      even no use of any antithrombotic or antiplatelet therapy was advocated. Given
      this ongoing dispute, the aim of this retrospective double-institutional study
      was to evaluate the necessity of antiplatelet treatment by ASA with no
      postoperative antiplatelet therapy in terms of survival, major bleedings and
      cerebral thromboembolism of patients undergoing biological AVR without
      thromboembolic risk factors. METHODS: From January 2001 to December 2003, 288
      consecutive patients (72.8+/-7.5 years, 134 males) with sinus rhythm and no other
      thromboembolic risk factors underwent single biological AVR with porcine or
      bovine pericardial valves without concurrent coronary artery bypass graft
      surgery. By surgeons preference, 100 mg ASA was given to 132 patients, and 156
      patients received no antiplatelet therapy. Patients were followed for cerebral
      ischemic events, major bleedings, need for repeat operation, NYHA class and
      survival at three time intervals postoperatively (30 days, 3 and 12 months).
      RESULTS: None of all patients died during the operation. Mortality within 30 days
      was 3.8% in the ASA and 3.9% in the no ASA group (p=0.777). There were no
      statistically significant differences for cerebral ischemia within 3 months after
      AVR (ASA 0.8% vs no ASA 1.3%: p=0.884) and 3 to 12 months after AVR (ASA 0.8% vs
      no ASA 0%; p=0.933). Major bleedings occurred in two ASA-treated patients and in
      one patient without antiplatelet therapy (p=0.884). The incidence of NYHA class
      III-IV after 3 months (1.5% vs 1.9%; p=0.850) and 12 months (9.0% vs 5.1%;
      p=0.278) were similar, as were the need for repeat operative AVR after 12 months
      (0.8% vs 0.6%; p=0.553). Survival rates at 12-month follow-up were 95.5% for ASA
      treatment and 94.9% for no ASA treatment (p=0.963). CONCLUSIONS: In patients
      without thromboembolic risk factors undergoing biological AVR administration of
      ASA confers no advantage compared to no antiplatelet therapy. Functional status,
      thromboembolic events and survival were not adversely affected by withholding any
      antiplatelet therapy. Guidelines need to be reviewed for the antithrombotic
      therapy of patients without risk factors undergoing bioprosthetic AVR.

PMID- 17449265
TI  - Detecting the Ademkiewicz artery: is it really necessary in everyday practice?

PMID- 17449266
TI  - Sleeve lobectomy. Is it valid for all cases of lung cancer?

PMID- 17449267
TI  - Combined heart and liver transplantation for familial amyloidotic neuropathy.
AB  - Familial amyloidotic polyneuropathy (FAP) is an inherited disease characterized
      by an abnormal systemic deposition of a mutant protein called transthyretin (TTR)
      with elective involvement of the peripheral nervous system, but often determining
      cardiac, gastrointestinal, and urinary tract dysfunction. FAP commonly affects
      the liver and the heart until end-organs failure. Transthyretin amyloidosis is
      today an accepted indication for orthotopic liver transplantation (OLT). Combined
      heart and liver transplantation (CHLT) may be an attractive and rational
      treatment option when both organs are contemporary involved by this type of
      amyloidotic disease. Nowadays, surgical indications and techniques are far from
      being consolidated because only few cases of CHLT have been previously reported
      in literature. From November 1999 to May 2006, we performed five orthotopic
      combined heart and liver transplantations for FAP at our institution. Our
      surgical experience and clinical outcomes are herein reported.

PMID- 17449268
TI  - Endovascular management of pseudo-aneurysms after previous surgical repair of
      congenital aortic coarctation.
AB  - OBJECTIVE: Whatever the surgical technique used, false aneurysm formation is one
      of the long-term complications of repair of aortic coarctation. Conservative
      management is associated with a 100% rate of rupture. The conventional surgical
      approach is complex and associated with high morbidity and mortality rates. We
      report our experience of endovascular management of pseudo-aneurysms after
      previous surgical repair of congenital aortic coarctation. METHODS: Between
      October 2005 and 2006, stent-grafting of pseudo-aneurysms after previous surgical
      repair of congenital aortic coarctation was performed in four patients. Median
      age was 31.5 years (range: 24-38). Two patients had undergone two previous
      interventions. The last previous surgery consisted of graft interposition (N=2),
      subclavian flap aortoplasty (N=1) and aorto-aortic bypass (N=1). Median size of
      the pseudo-aneurysm was 31.5mm (range: 20-58). Mean time between the last surgery
      and endovascular treatment was 24 years (range: 3-32). One patient was treated
      emergently because of hemoptysis in relation with an aorto-bronchial fistula, the
      three other patients were treated electively. A transfemoral approach was used in
      all patients. The Zenith TX2 (Cook) thoracic stent-graft was used in all the
      patients, one patient underwent previous dilatation at the coarctation level.
      When present, the ostium of the left subclavian artery was always covered (N=3).
      RESULTS: No major complication occurred during the procedure and no patient died
      during the follow-up. One patient presented a type II endoleak which
      spontaneously healed during the first month. Another patient with his left
      subclavian artery covered presented claudication of the left arm requiring a
      carotid-subclavian bypass. After a median follow-up of 7.5 months (range: 1
      12.9), the patients were asymptomatic and CT scans demonstrated complete
      exclusion of all treated postcoarctation aneurysms without recoarctation and
      without any stent-graft-related complication. CONCLUSIONS: The endovascular
      management of pseudo-aneurysms after previous surgical repair of congenital
      aortic coarctation is feasible. This approach was safe and effective. Long-term
      clinic and imaging follow-up is mandatory.

PMID- 17449270
TI  - Determination of growth inhibitory action point of interferon gamma on WISH cells
      in cell cycle progression and the window of responsiveness of the cells to the
      interferon.
AB  - We had earlier shown that human foetal epithelial cells (WISH), growth-inhibited
      by interferon gamma (IFNgamma), were reversibly detained at a point prior to DNA
      synthesis. In the present study, we determined the window of action of IFNgamma
      in the G1 phase duration and the exact point of detention of WISH cells in cell
      cycle progression with respect to the known points of detention by the inhibitors
      of DNA replication initiation (aphidicolin and carbonyl diphosphonate) and of
      activation of replication protein A (6-dimethylaminopurine), of which RPA
      activation being the earlier event compared to DNA replication initiation in cell
      cycle progression. WISH cells, which were released from IFNgamma-induced arrest,
      permeabilised and exposed independently to these inhibitors show that IFNgamma
      detains WISH cells prior to initiation of DNA synthesis. Further, exposure of
      IFNalpha-synchronized (at G0/G1) or mimosine-synchronized (at G1/S) WISH cells to
      IFNgamma, which was added at different time points post-release from the
      synchronizing agent, showed that the cells were promptly responsive to the growth
      inhibitory action of IFNgamma only during the first 11h in G1 phase. Taken
      together, these results suggest that IFNgamma inhibits growth of WISH cells by
      detaining them at a point prior to initiation of DNA synthesis and that the IFN
      acts within the first 11h in G1 phase of the cell cycle.

PMID- 17449269
TI  - Three is better than one: pre-ligand receptor assembly in the regulation of TNF
      receptor signaling.
AB  - The tumor necrosis factor (TNF) family of cytokines and their receptors regulates
      many areas of metazoan biology. Specifically, this cytokine-receptor family plays
      crucial roles in regulating myriad aspects of immune development and functions.
      Disruption of ligand-receptor interaction or downstream signal transduction
      components in the TNF family often leads to pathological conditions.
      Historically, members of the TNF receptor family (TNFRs) were thought to exist as
      monomeric receptor chains prior to stimulation. Binding of the trimeric ligand
      then induces the trimerization of the receptors and activation of downstream
      signaling. However, recent evidence indicates that many TNFRs exist as pre
      assembled oligomers on the cell surface. Pre-ligand assembly of TNFR oligomers is
      mediated by the pre-ligand assembly domain (PLAD), which resides within the
      membrane distal cysteine-rich domain of the receptors. Growing evidence indicates
      that PLAD-mediated receptor association regulates cellular responses to TNF-like
      cytokines, especially in cells of the immune system. Thus, targeting pre-ligand
      assembly may offer new possibilities for therapeutic intervention in different
      pathological conditions involving TNF-like cytokines.

PMID- 17449271
TI  - Effect of storage temperatures on the stability of cytokines in cervical mucous.
AB  - Cytokines have progressively come to serve as indicators for the presence or
      severity of a disease. But accurate measurement of cytokine levels can be
      deterred by lack of proper handling and storage of the samples. In this study, we
      attempted to measure the effect of snap-freezing and refrigeration at the time of
      collection on cervical mucous. Luminex analyses of the frozen and refrigerated
      pairs exhibited no significant differences in levels for 7 out of the 10
      cytokines measured simultaneously. The cytokines TNF-alpha, IFN-gamma and IL
      1beta, were significantly different between the pairs with the refrigerated
      samples showing higher levels for each of these cytokines. The results suggest
      that refrigeration of mucous samples immediately after collection would allow for
      better conservation of the cytokines in cervical mucous.

PMID- 17449272
TI  - Role of interleukin-1beta in the control of neuroepithelial proliferation and
      differentiation of the spinal cord during development.
AB  - Interleukin-1beta (IL-1beta) is an important trophic factor in the nervous system
      (NS). IL-1beta is ubiquitously expressed from very early stages during the
      development of the amphibian NS and its action has been demonstrated in vitro on
      survival, proliferation and differentiation in mammalian embryos. In this report,
      we show that IL-1beta is immunocytochemically expressed in embryonic spinal cord
      from early stages, both in rat (embryonic day 12) and in chicken (stage 17-HH),
      in neuroepithelial cells and nerve fibres, dorsal root ganglia, anterior and
      posterior roots of the spinal nerves, and in the fibres of these nerves. Our in
      vivo experiments on chick embryos, with microbeads impregnated with IL-1beta
      implanted laterally to the spinal cord at the level of the wing anlage,
      demonstrate that this cytokine produces a statistically significant increase in
      nuclear incorporation of BrdU at the dorsal level and a reduction of this at the
      ventral level, whereas local immunoblocking with anti-IL-1beta antibodies causes
      a dorsal reduction of BrdU incorporation and alters ventral differentiation.
      These data demonstrate that IL-1beta plays a part in controlling proliferation
      and early differentiation during the development of the spinal cord in chick
      embryos.

PMID- 17449273
TI  - 7.87 eV laser desorption postionization mass spectrometry of adsorbed and
      covalently bound bisphenol A diglycidyl methacrylate.
AB  - Bisphenol A diglycidyl methacrylate (Bis-GMA) was adsorbed onto or covalently
      bound to a porous silicon oxide surface. Laser desorption 10.5 eV postionization
      mass spectrometry (LDPI-MS) was previously demonstrated for surface analysis of
      adsorbed and surface bound Bis-GMA, but signal to noise levels were low and ion
      fragmentation was extensive. 7.87 eV postionization using the fluorine laser was
      demonstrated here for Bis-GMA. However, signal levels remained low for LDPI-MS of
      Bis-GMA as its ionization potential (IP) was only approximately 7.8 eV, near
      threshold for single photon ionization by the 7.87 eV fluorine laser. It is known
      that aromatic tagging of molecular analytes can lower the overall IP of the
      tagged molecular complex, allowing 7.87 eV single photon ionization. Therefore,
      Bis-GMA was also derivatized with several tags whose IPs were either below or
      above 7.87 eV: the tag with an IP below 7.87 eV enhanced single photon ionization
      while the tags with higher IPs did not. However, signal intensities were enhanced
      by resonant laser desorption for two of the derivatized Bis-GMAs. Intact ions of
      Bis-GMA and its derivatives were generally observed by 7.87 eV LDPI-MS,
      consistent with the formation of ions with relatively little internal energy upon
      threshold single photon ionization.

PMID- 17449274
TI  - Large scale preparation of recombinant human parathyroid hormone 1-84 from
      Escherichia coli.
AB  - Human parathyroid hormone (hPTH) is a promising agent in the treatment of
      osteoporosis. The intact recombinant human parathyroid hormone [rhPTH(1-84)] was
      prepared in a large scale from Escherichia coli using a soluble fusion protein
      strategy. With degenerate codons, gene of hPTH(1-84) was synthesized, ligated
      with pET32a(+) vector, and then expressed in E. coli BL21(DE3) cells. The soluble
      fusion protein His(6)-thioredoxin-hPTH(1-84) was harvested after purification by
      immobilized metal affinity chromatography (IMAC). Following enterokinase
      cleavage, ion-exchange-chromatography (IEC) and size-exclusive-chromatography
      (SEC) were used, and finally, over 300mg/l intact hPTH(1-84) with high purity up
      to 99% was obtained. The purified rhPTH(1-84) was confirmed by mass spectrometry
      and N-terminal/C-terminal amino-acid sequence analysis. Additionally, this
      product stimulated adenylate cyclase in Rat Osteosarcoma Cell UMR-106 at the same
      extent as hPTH standards, indicating that the purified rhPTH(1-84) has full
      biological activity. The efficient procedure for expression and purification of
      rhPTH(1-84) may be useful for the mass production of this important protein.

PMID- 17449275
TI  - Difference in Japanese flounder, Paralichthys olivaceus gene expression profile
      following hirame rhabdovirus (HIRRV) G and N protein DNA vaccination.
AB  - The glycoprotein (G protein) gene, but not other genes, of fish rhabdoviruses,
      when used as a DNA vaccine was previously shown to be highly effective in
      inducing a protective immune response. In this study we used a DNA microarray to
      examine differential gene expression in Japanese flounder (Paralichthys
      olivaceus) in response to a DNA vaccine made from the genes of hirame rhabdovirus
      (Rhabdovirus olivaceus) (HIRRV) G protein (pHRV-G) and nucleocapsid (N) protein
      (pHRV-N). A high level of protection against HIRRV infection was observed
      following vaccination with the pHRV-G but no protection was observed following
      vaccination with the pHRV-N. Microarray analyses showed that the set of genes
      induced by pHRV-G was different from the set induced by pHRV-N. Specifically,
      five genes (Interferon-stimulated gene, 15kDa (ISG15), Interferon-stimulated
      gene, 56kDa (ISG56), Mx and two unknown genes) were strongly induced after
      injection by the pHRV-G but not pHRV-N and three of these genes are known as type
      I IFN-inducible genes. Poly I:C, a known inducer of type I interferon that
      elicits immune response similar to that elicited by a virus infection, also
      induced these five genes in kidney cells. These results suggest that in order to
      be effective and confer protection, vaccines against HIRRV and probably fish
      rhabdoviruses may need to stimulate the type I IFN system.

PMID- 17449276
TI  - The ontogeny and extrahepatic expression of complement factor C3 in Atlantic
      salmon (Salmo salar).
AB  - Fish embryos and hatchlings are exposed to pathogens long before maturation of
      their lymphoid organs. Little is known about defence mechanisms during the
      earliest stages of life, but innate mechanisms may be essential for survival. The
      complement system in fish is well developed and represents a major part of innate
      immunity. Complement factor 3 (C3) is central subsequent to activation of all
      pathways of the complement system, leading to inflammatory reactions, such as
      chemotaxis, opsonisation and lysis of pathogens. Hepatocytes represent the major
      source of C3, but modern molecular biological methods have confirmed that C3 is
      synthesised at multiple sites. Our main objective was to study the ontogeny of C3
      in Atlantic salmon by mapping the commencement of synthesis and localisation of
      proteins. Eggs, embryos, hatchlings and adult fish were analysed for the presence
      of C3 mRNA and proteins. From immunohistochemical studies, C3 proteins were
      detected at several extrahepatic sites, such as the skeletal muscle, developing
      notochord and chondrocytes of the gill arch. Immunoblotting revealed presence of
      C3 proteins in the unfertilised egg, but C3 mRNA was only detected after
      fertilisation by real-time RT-PCR. Taken together, the results implicated the
      maternal transfer of C3 proteins as well as novel non-immunological functions
      during development.

PMID- 17449277
TI  - Adaptive evolution after duplication of penaeidin antimicrobial peptides.
AB  - Penaeidin antimicrobial peptides in penaeid shrimps are an important component of
      their innate immune system that provides immunity against infection caused by
      several gram-positive bacteria and filamentous fungal species. Despite the
      knowledge on the identification and characterization of these peptides in penaeid
      shrimps, little is known about the evolutionary pattern of these peptides and the
      underlying genetic mechanisms that maintain high sequence diversities in the
      penaeidin gene family. Based on the phylogenetic analyses and maximum likelihood
      based codon substitution analyses, here we present the convincing evidence that
      multiple copies of penaeidins have evolved by gene duplication, and positive
      Darwinian selection (adaptive evolution) is the likely cause of accelerated rate
      of amino acid substitutions among these duplicated genes. While the average ratio
      of non-synonymous to synonymous substitutions (omega) for the entire coding
      region of both active domains is 0.9805, few codon sites showed significantly
      higher omega (3.73). The likelihood ratio tests that compare models incorporating
      positive selection (omega>1) at certain codon sites with models not incorporating
      positive selection (omega<1), failed to reject (p=0) the evidence of positive
      Darwinian selection. The rapid adaptive evolution of this gene family might be
      directed by the pathogens and the faster rate of amino acid substitutions in the
      N-terminal proline-rich and C-terminal cysteine-rich domains could be due to
      their direct involvement in the protection against pathogens. When the host
      expose to different habitats/environment an accelerated rate of amino acid
      substitutions in both the active domains may also be expected.

PMID- 17449278
TI  - Lumbar-pelvic range and coordination during lifting tasks.
AB  - Spine motion has been described to have two regions, a neutral zone where lumbar
      rotation can occur with little resistance and an elastic zone where structures
      such as ligaments, facet joints and intervertebral disks resist rotation. In
      vivo, the passive musculature can contribute to further limiting the functional
      neutral range of lumbar motion. Movement out of this functional neutral range
      could potentially put greater loads on these structures. In this study, the range
      of lumbar curvature rotation was examined in twelve healthy, untrained volunteers
      at four torso inclination angles. The lumbar curvature during straight-leg
      lifting tasks was then defined as a percentage of this range of possible lumbar
      curvatures. Subjects were found to remain neutrally oriented during the flexion
      phase of a lifting task. During the extension phase of the lifting task, however,
      subjects were found to assume a more kyphotic posture, approaching the edge of
      the functional range of motion. This was found to be most pronounced for heavy
      lifting tasks. By allowing the lumbar curvature to go into a highly kyphotic
      posture, subjects may be taking advantage of stretch-shortening behavior in
      extensor musculature and associated tendons to reduce the energy required to
      raise the torso. Such a kyphotic posture during extension, however, may put
      excessive loading on the elastic structures of the spine and torso musculature
      increasing the risk of injury.

PMID- 17449279
TI  - Tennis players show a lower coactivation of the elbow antagonist muscles during
      isokinetic exercises.
AB  - PURPOSE: Previous studies have suggested that muscle coactivation could be
      reduced by a recurrent activity (training, daily activities). If this was
      correct, skilled athletes should show a specific muscle activation pattern with a
      low level of coactivation of muscles which are typically involved in their
      discipline. In particular, the aim of this study was to verify the hypothesis
      that the amount of antagonist activation of biceps brachii (BB) and triceps
      brachii (TB) is different between tennis players and non-players individuals
      during maximal isokinetic contractions. METHODS: Ten young healthy men and eight
      male tennis players participated in the study. The surface electromyographic
      signals (sEMG) were recorded from the BB and TB muscles during three maximal
      voluntary isometric contractions (MVC) of elbow flexors and extensors and a set
      of three maximal elbow flexions and extensions at 15 degrees , 30 degrees , 60
      degrees , 120 degrees , 180 degrees and 240 degrees /s. Normalized root mean
      square (RMS) of sEMG was calculated as an index of sEMG amplitude. RESULTS:
      Antagonist activation (%RMSmax) of TB was significantly lower in tennis players
      (from 14.0+/-7.9% at MVC to 16.3+/-8.9% at 240 degrees /s) with respect to non
      players (from 27.7+/-19.7% at MVC to 38.7+/-17.6% at 240 degrees /s) at all
      angular velocities. Contrary to non-players, tennis players did not show any
      difference in antagonist activation between BB and TB muscles. CONCLUSIONS:
      Tennis players, with a constant practice in controlling forces around the elbow
      joint, learn how to reduce coactivation of muscles involved in the control of
      this joint. This has been shown by the lower antagonist muscular activity of
      triceps brachii muscle during isokinetic elbow flexion found in tennis players
      with respect to non-players.

PMID- 17449280
TI  - Musculature and biomechanics of the trunk in the maintenance of upright posture.
AB  - Surface perturbation has been used for decades to study balance and postural
      control; however the behavior of the trunk in these postural responses has been
      largely overlooked. Thirteen healthy males (18-23 yrs) were exposed to horizontal
      support surface translations delivered randomly in one of eight different
      horizontal directions in both sitting and standing. A 4-segment model of the
      trunk was used to estimate the kinematics and kinetics associated with the
      postural response, while surface EMG was acquired, bilaterally, from seven trunk
      muscles and one hip muscle. Multi-segmental movement was observed in the trunk in
      both test postures. Both the biomechanical and neuromuscular aspects of the trunk
      response were significantly affected by translation direction and test posture,
      with an interaction effect between these variables. The response in sitting was
      closely tied to the movement of the support surface, while the response in
      standing occurred in two phases: the first related to the dynamic response in the
      lower limbs, and the second tied to the movement of the support surface. As such,
      the observed postural responses could be largely explained by the biomechanical
      constraints of the system, such that the neural control of trunk equilibrium is
      simplified.

PMID- 17449281
TI  - Intra-session repeatability of lower limb muscles activation pattern during
      pedaling.
AB  - Assessment of intra-session repeatability of muscle activation pattern is of
      considerable relevance for research settings, especially when used to determine
      changes over time. However, the repeatability of lower limb muscles activation
      pattern during pedaling is not fully established. Thus, we tested the intra
      session repeatability of the activation pattern of 10 lower limb muscles during a
      sub-maximal cycling exercise. Eleven triathletes participated to this study. The
      experimental session consisted in a reference sub-maximal cycling exercise (i.e.
      150 W) performed before and after a 53-min simulated training session (mean power
      output=200+/-12 W). Repeatability of EMG patterns was assessed in terms of muscle
      activity level (i.e. RMS of the mean pedaling cycle and burst) and muscle
      activation timing (i.e. onset and offset of the EMG burst) for the 10 following
      lower limb muscles: gluteus maximus (GMax), semimembranosus (SM), Biceps femoris
      (BF), vastus medialis (VM), rectus femoris (RF), vastus lateralis (VL),
      gastrocnemius medianus (GM) and lateralis (GL), soleus (SOL) and tibialis
      anterior (TA). No significant differences concerning the muscle activation level
      were found between test and retest for all the muscles investigated. Only VM, SOL
      and TA showed significant differences in muscle activation timing parameters.
      Whereas ICC and SEM values confirmed this weak repeatability, cross-correlation
      coefficients suggest a good repeatability of the activation timing parameters for
      all the studied muscles. Overall, the main finding of this work is the good
      repeatability of the EMG pattern during pedaling both in term of muscle activity
      level and muscle activation timing.

PMID- 17449283
TI  - Sorting wheat from chaff in multi-gene analyses of chlorophyll c-containing
      plastids.
AB  - Photosynthetic eukaryotes contain primary, secondary or tertiary plastids,
      depending on the source of the organelle (a cyanobacterium or a photosynthetic
      eukaryote). Plastid phylogeny is relatively well investigated, but molecular
      phylogenies have conflicted as a function of gene choice, taxon-representations,
      and analytical method. To better understand the influences of these variables, we
      performed analyses of a multi-gene data set based on 62 plastid-associated genes
      of 15 taxa representing the major plastid lineages. In an attempt to distinguish
      phylogenetic signal from non-phylogenetic patterns, we analyzed the data using a
      wide range of phylogenetic methods and examined the effect of covarion evolution
      and compositional bias. The data suggest that the chlorophyll c-containing
      plastids are monophyletic and acquired their plastids from the red algae after
      the emergence of the Cyanidiales. The relationships among chl c-containing
      plastids are particularly hard to resolve. This is the largest data set used for
      this purpose; the analyses show that cryptophyte plastids are sister to other chl
      c-containing plastids, and haptophyte and peridinin-containing dinoflagellate
      plastids are closely related.

PMID- 17449282
TI  - Using a reference tissue model with spatial constraint to quantify
      [11C]Pittsburgh compound B PET for early diagnosis of Alzheimer's disease.
AB  - INTRODUCTION: Reference tissue model (RTM) is a compartmental modeling approach
      that uses reference tissue time activity curve (TAC) as input for quantification
      of ligand-receptor dynamic PET without blood sampling. There are limitations in
      applying the RTM for kinetic analysis of PET studies using [11C]Pittsburgh
      compound B ([11C]PIB). For region of interest (ROI) based kinetic modeling, the
      low specific binding of [11C]PIB in a target ROI can result in a high linear
      relationship between the output and input. This condition may result in
      amplification of errors in estimates using RTM. For pixel-wise quantification,
      due to the high noise level of pixel kinetics, the parametric images generated by
      RTM with conventional linear or nonlinear regression may be too noisy for use in
      clinical studies. METHODS: We applied RTM with parameter coupling and a
      simultaneous fitting method as a spatial constraint for ROI kinetic analysis.
      Three RTMs with parameter coupling were derived from a classical compartment
      model with plasma input: an RTM of 4 parameters (R(1), k'(2R), k(4), BP) (RTM4P);
      an RTM of 5 parameters (R(1), k(2R), NS, k(6), BP) (RTM5P); and a simplified RTM
      (SRTM) of 3 parameters (R(1), k'(2R), BP) (RTM3P). The parameter sets [k'(2R),
      k(4)], [k(2R), NS, k(6)], and k'(2R) are coupled among ROIs for RTM4P, RTM5P, and
      RTM3P, respectively. A linear regression with spatial constraint (LRSC) algorithm
      was applied to the SRTM for parametric imaging. Logan plots were used to estimate
      the distribution volume ratio (DVR) (=1+BP (binding potential)) in ROI and pixel
      levels. Ninety-minute [11C]PIB dynamic PET was performed in 28 controls and 6
      individuals with mild cognitive impairment (MCI) on a GE Advance scanner. ROIs of
      cerebellum (reference tissue) and 15 other regions were defined on coregistered
      MRIs. RESULTS: The coefficients of variation of DVR estimates from RTM3P obtained
      by the simultaneous fitting method were lower by 77-89% (in striatum, frontal,
      occipital, parietal, and cingulate cortex) as compared to that by conventional
      single ROI TAC fitting method. There were no significant differences in both TAC
      fitting and DVR estimates between the RTM3P and the RTM4P or RTM5P. The DVR in
      striatum, lateral temporal, frontal and cingulate cortex for MCI group was 25% to
      38% higher compared to the control group (p < or = 0.05), even in this group of
      individuals with generally low PIB retention. The DVR images generated by the
      SRTM with LRSC algorithm had high linear correlations with those from the Logan
      plot (R2 = 0.99). CONCLUSION: In conclusion, the RTM3P with simultaneous fitting
      method is shown to be a robust compartmental modeling approach that may be useful
      in [11C]PIB PET studies to detect early markers of Alzheimer's disease where
      specific ROIs have been hypothesized. In addition, the SRTM with LRSC algorithm
      may be useful in generating R(1) and DVR images for pixel-wise quantification of
      [11C]PIB dynamic PET.

PMID- 17449285
TI  - Rapid contact call-driven induction of NR2A and NR2B NMDA subunit mRNAs in the
      auditory thalamus of the budgerigar (Melopsittacus undulatus).
AB  - In situ hybridization histochemistry was used to assess the effect of auditory
      stimulation with natural contact calls on expression of NR2A and NR2B NMDA
      subunit mRNAs in neurons of the thalamic auditory relay nucleus ovoidalis (Ov) of
      a vocal learning parrot species, the budgerigar (Melopsittacus undulatus). The
      results showed that both the core (Ov) and ventromedial shell subdivisions (Ovm)
      of ovoidalis contained neurons expressing NR2A and NR2B mRNA in no-stimulation
      control subjects and that the distributions of neurons expressing these subunit
      mRNAs were very similar in both the core and shell of Ov. Contact call
      stimulation (5, 30 and 180 min) resulted in substantial increases of 50-60% in
      the number of neurons expressing NR2A and NR2B mRNAs in both the core and shell.
      Staining intensity, as measured by the optical density of stained somata
      approximately doubled compared to controls for both NR2 subunits in the 5 and 30
      min conditions, but declined from 30 to 180 min. In all conditions, the density,
      but not staining intensity, of neurons expressing NR2B exceeded NR2A expression.
      Furthermore, the density of neurons expressing both subunit mRNAs in call
      stimulation conditions was greater in the core than in the shell despite the fact
      that total neuronal density was approximately 20% higher in the shell. Previous
      experiments have shown that call stimulation is more effective at inducing
      expression of the immediate early gene zenk in the Ov shell than core; however
      the present results do not indicate that either NR2A or NR2B mRNA expression
      mediates this effect since neither subunit exhibits greater expression in Ovm.
      Ca(++) release is needed for immediate early gene expression, however and,
      notably, Ovm contains large numbers of neurons containing CGRP, a peptide which
      has been shown to increase cytosolic Ca(++) levels.

PMID- 17449284
TI  - Cholinergic lesions produce task-selective effects on delayed matching to
      position and configural association learning related to response pattern and
      strategy.
AB  - 192IgG-saporin (SAP) was used to selectively destroy cholinergic neurons in the
      rostral basal forebrain (e.g., medial septum (MS) and vertical limb of the
      diagonal band of Broca (VDB)) and/or the caudal basal forebrain (e.g., nucleus
      basalis magnocellularis (NBM)) of ovariectomized Sprague-Dawley rats. The effects
      of these lesions on two different cognitive tasks, a delayed matching to position
      (DMP) T-maze task, and a configural association (CA) operant conditioning task,
      were evaluated and compared. Injecting SAP into either the MS or NBM
      significantly impaired acquisition of the DMP task. Analysis showed that the
      effects were due largely to an affect on response patterns adopted by the rats
      during training, as opposed to an effect on working memory performance. Notably,
      the impairment in DMP acquisition did not correlate with the degree of
      cholinergic denervation of the hippocampus. Despite the deficit, most animals
      eventually learned the task and reached criterion; however by the end of
      training, controls and animals that received SAP into either the MS or NBM
      appeared more likely to use an allocentric place strategy to solve the task,
      whereas animals that received SAP into both the MS and NBM were more likely to
      use an egocentric response strategy. Cholinergic lesions also produced a small
      but significant affect on acquisition of the CA task, but only with respect to
      response time, and only in the SAP-NBM-treated animals. SAP-NBM lesions also
      produced small but significant impairments in both the number of responses and
      response time during the acquisition of simple associations, possibly reflecting
      an effect on alertness or attention. Notably, the effects on CA acquisition were
      small, and like the effects on DMP acquisition did not correlate with the degree
      of cholinergic denervation of the hippocampus. We conclude that selective basal
      forebrain cholinergic lesions produce learning deficits that are task specific,
      and that cholinergic denervation of either the frontal cortex or hippocampus can
      affect response patterns and strategy in ways that affect learning, without
      necessarily reflecting deficits in working memory performance.

PMID- 17449286
TI  - Deep penetrating nevus of cheek skin.
AB  - Deep penetrating nevus is a cutaneous pigmented lesion first reported by Seab et
      al. in 1989. The skin of the face and neck region is one of the most common sites
      for deep penetrating nevus. Despite this prevalence in the head and neck region,
      deep penetrating nevus has not previously been discussed in journals emphasizing
      oral and maxillofacial pathology. The purpose of this case report is to present
      this rare entity to the oral pathology community, emphasizing its common
      presenting histologic features of a combined nevus.

PMID- 17449287
TI  - Persistent endodontic lesion due to complex cementodentinal tears in a maxillary
      central incisor--a case report.
AB  - The cementodentinal tear is rarely detected by noninvasive procedures owing to
      its clinical picture simulating a root fracture or a periodontal or endodontic
      lesion. We present a case of complex cementodentinal tears in a 79-year-old woman
      who presented a repeated swelling at the labial mucosa of the left maxillary
      central incisor for 6 months. Periapical radiographs demonstrated a vertical
      radiolucent fracture line extending from the root apex along the mesial aspect of
      the root to near the middle portion of the root of the left maxillary central
      incisor. Because endodontic re-treatment failed to cure the disease, periapical
      surgery was performed, and 2 fractured U-shaped root fragments around the apical
      root surface were removed. Histologic examination showed that the 2 fractured
      root fragments were composed mainly of the dentin covered by a thin layer of the
      cementum and overlying periodontal ligament tissue, suggesting cementodentinal
      tears. A swelling recurred 8 months after the initial operation. Therefore, a
      second periapical surgery was performed. Although no obvious fracture line was
      observed around the root surface, the second surgery did not cure the disease,
      either. A persistent small swelling was noted at the alveolar mucosa of the
      affected tooth during the follow-up. We conclude that although a cementodentinal
      tear can be detected by a careful radiographic examination, its clinical outcome
      is not predictable by surgical removal only.

PMID- 17449288
TI  - A l2-month longitudinal in vitro leakage study on a new silicon-based root canal
      filling material (Gutta-Flow).
AB  - OBJECTIVE: This study was performed to determine in vitro the short- and long
      term sealing ability of a recently developed silicon-based root canal filling
      material (Gutta-Flow). STUDY DESIGN: Sixty human upper central incisors were
      divided into 3 groups (n = 20). The root canals were instrumented and obturated
      with laterally compacted gutta-percha and AH26 sealer (group 1), continuous-wave
      thermal compaction (System B technique) and AH26 sealer (group 2), and Gutta-Flow
      technique (group 3). Leakage along entire root canal fillings was measured by the
      movement of an air bubble in a micropipette connected to the experimental root
      using a fluid-transport model. Short-term leakage measurements were carried out
      for 3 hours after 24 hours of equilibrium establishment. Leakage was measured
      again and at 3, 6, and 12 months after the initial measurement. RESULTS: At the 3
      hour measurement, no significant differences were found among the 3 experimental
      groups. Long-term leakage measurements showed that at 3 and 6 months no
      significant differences were existed between Gutta-Flow and the other 2
      techniques. However, at 12 months, root canal fillings with Gutta-Flow leaked
      significantly less than fillings of lateral compaction and System B technique.
      CONCLUSIONS: Gutta-Flow technique showed a similar sealing ability to either
      lateral compaction or System B technique. This comparison improved significantly
      over time. These findings may be related to the possible expanding capacity of
      the material and the partial dissolution of the sealer over time in the other 2
      groups.

PMID- 17449289
TI  - Surgical treatment of Aspergillus mycetomas of the maxillary sinus: review of the
      literature.
AB  - The present study reviews the literature concerning the surgical treatment of
      Aspergillus mycetoma (AM) in the last 20 years to identify a gold standard
      surgical technique. Aspergillus mycetoma of the maxillary sinus, or mycetoma
      (fungus ball), is a noninvasive or extramucosal mycotic infection. Surgical
      removal of the sinus fungal masses to ensure drainage and aeration is performed
      using the traditional Caldwell-Luc (CL) procedure or endoscopic sinus surgery
      (ESS). Results of this review suggest that the gold standard surgical technique
      for AM is ESS with middle meatal antrostomy. General or local antifungal drugs
      are not indicated. Combined approach with an intraoral surgical access from the
      anterolateral wall of the maxillary sinus has to be reserved for selected cases
      in which ESS doesn't permit complete extraction of all fungal concretions or
      foreign bodies. The CL procedure should be avoided, because it has detrimental
      consequences for sinus physiology.

PMID- 17449290
TI  - The effect of mandibular distraction osteogenesis on the histology and
      immunohistology of keratinized gingiva.
AB  - OBJECTIVES: We investigated distracted keratinized epithelium to elucidate any
      proliferative and degenerated changes and to estimate the stability of the
      gingival tissues in mandibular distraction osteogenesis in a rabbit model. STUDY
      DESIGN: Twenty-two rabbits were subjected to unilateral vertical osteotomy. After
      a latency period of 4 days, devices were activated 3, 6, and 10 days at a rate of
      1 mm/day. We additionally investigated the recovery of the distracted gingiva in
      consolidation periods for 3 weeks. The animals were examined by histologic and
      immunohistologic methods using proliferating cell nuclear antigen (PCNA), single
      stranded DNA (ssDNA), and keratin. RESULTS: Atrophy of distracted gingiva was
      observed characterized by loss of rete ridges, acanthosis, vacuolation in the
      prickle cell layer, and cleavage of the keratin layer. Proliferating cell nuclear
      antigen-positive cells and ssDNA-positive cells were observed in the basal and
      prickle layers, respectively. During consolidation periods, slight recovery of
      rete ridges, thinning of the keratin layer, and immature epithelial layer was
      observed. CONCLUSIONS: Proliferative and degenerated changes occurred to
      compensate for cell death and distracted space. Thickness of gingival tissues was
      maintained by high mitotic activity and delay in the rate of cell maturation.
      Immature epithelial layer was related to sensitive and weak resistance against
      various stimulating factors, such as cleavage of the keratin layer among
      distracted gingival tissues.

PMID- 17449291
TI  - Influence of immediate and delayed post space preparation on sealing ability of
      resilon.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of immediate and
      delayed post space preparation on the sealing ability of a new root canal filling
      material. STUDY DESIGN: Seventy-two extracted teeth were prepared and obturated
      with gutta-percha/AH-Plus and Resilon/Epiphany sealer by the lateral compaction
      technique. The teeth were divided randomly into 4 groups, and the post space was
      prepared either immediately after filling or after the obturated teeth had been
      stored in saline at 37 degrees C for a week. Leakage was determined by a fluid
      transport device. RESULTS: The results showed that immediate post space
      preparation of the Resilon/Epiphany-filled group had a mean leakage value of 0.81
      microL/h, whereas the delayed preparation had a mean leakage value of 0.75
      microL/h. No difference (P > .05) in microleakage was found between gutta
      percha/AH-Plus and Resilon/Epiphany-filled groups after immediate preparation.
      There was significant difference between gutta-percha/AH-Plus and
      Resilon/Epiphany groups in the delayed post space preparation (P < .05).
      CONCLUSION: Epiphany/Resilon obturation achieved better sealing than gutta
      percha/AH-Plus at the apical end, especially in delayed post space preparation
      when mechanical techniques were used.

PMID- 17449292
TI  - Rapidly growing mass of the anterior maxillary gingiva.

PMID- 17449293
TI  - Multiple orofacial intraneural perineuriomas in a patient with hemifacial
      hyperplasia.
AB  - Perineurioma is a rare benign nerve sheath tumor derived of perineurial cells.
      There are two main types of perineurioma which differ histologically and
      clinically: intraneural and extraneural (soft tissue) perineurioma. Intraoral
      perineurioma is extremely rare. This report describes a case of multiple
      orofacial intraneural perineuriomas in a patient with hemifacial hyperplasia and
      discusses clinical, histologic, and ultrastructural features as well as
      differential diagnosis of perineuriomas, with emphasis on intraneural
      perineurioma.

PMID- 17449294
TI  - Oral and maxillofacial manifestations of Gardner's syndrome associated with
      growth hormone deficiency: case report and literature review.
AB  - Gardner's syndrome (GS) is a hereditary disorder inherited as autosomal dominant
      with complete penetrance and variable expression. GS is a variant of familial
      adenomatous polyposis characterized by extracolonic manifestations including
      osteomas, dental anomalies, and epidermoid cysts. The association between GS and
      endocrine abnormalities has been well documented but a direct pituitary
      involvement has never been reported. We present a case of oral and maxillofacial
      manifestations in an adult patient affected by GS associated with growth hormone
      deficiency, a hitherto unreported association. The possible pathogenic mechanisms
      are discussed.

PMID- 17449295
TI  - A ligneous periodontitis and conjunctival lesions in a patient with plasminogen
      deficiency.
AB  - Destructive membranous periodontal disease is a rare and poorly defined entity
      that is a part of a systemic disease due to accumulation of fibrin material. The
      disease is characterized by gingival enlargement and periodontal tissue
      destruction that leads to rapid bone loss despite treatment efforts. We present a
      case with ligneous periodontitis and conjunctivitis.

PMID- 17449296
TI  - Clinical and scanning electron microscopic features of invasive cervical
      resorption in a maxillary molar.
AB  - This case report presents clinical and morphological features of severe invasive
      cervical resorption (ICR) involving a maxillary first molar. Surface morphology
      of the ICR defect that extended into enamel was studied using a scanning electron
      microscope. The topography and morphology of resorbed enamel and pulpal surfaces
      are described. The pulpal space was characterized by proliferation of
      fibrovascular tissue invaded by a number of > or = 15-microm-large
      dentinoclastlike cells. The vertical orientation and hexagonal geometric outlines
      of enamel rods indicated that the resorptive defect had extended into the outer
      surface of enamel. Preferential odontoclastic dissolution of interprismatic
      enamel was noted. Deposits of a cementumlike substance were noticed on enamel
      surfaces, indicating that resorptive process was coupled with repair. Complete
      destruction of dentin was associated with no response by the tooth to cold
      stimulus, supporting the hydrodynamic theory of dentinal sensitivity. The results
      of this study indicate that in addition to predentin and cementum, the outer
      surface enamel may be resistant to the resorptive process as well.

PMID- 17449297
TI  - Comparison of occlusal condition and prevalence of bone change in the condyle of
      patients with and without temporomandibular disorders.
AB  - OBJECTIVE: The purpose of this study was to compare the differences in dental and
      occlusal conditions, and prevalence of bone change in the condyle, between a
      group of patients with temporomandibular disorders (TMD) and a group of dental
      patients without such complaints. STUDY DESIGN: A group of 504 patients with
      temporomandibular disorders (TMD patients) and a group of 970 patients without
      such complaints (dental patients), all 25 years of age or older, were compared
      using the criteria of age, sex, dental and occlusal condition, and prevalence of
      bone change in the condyle based on panoramic radiographs and imaging request
      forms. RESULTS: In both groups, the rate of complete dental arch was high for
      both jaws. According to Eichner's index, the rate for group A among the dental
      patients was 59.6%, whereas it was 84.7% in the TMD patients (P < .01). The
      prevalence of bone change in the condyle was 17.7% for the TMD patients and 11.6%
      for the dental patients (P < .01). Eichner's group C was somewhat high for the
      dental patients, and group A was high for the TMD patients. However, there were
      no significant differences in the occlusal conditions based on the prevalence of
      bone change. Deformity was the most common abnormality of bone change for both
      the dental and the TMD patients. In the TMD patients, the rate of osteophytes was
      the second most common abnormal finding. Osteophytes were the highest among the
      average age for all abnormal bone changes in the condyle. With the TMD patients,
      all the changes were more commonly found in Eichner's group A. CONCLUSIONS: It
      was demonstrated that the symptoms of TMD correlated with age, sex, and dental
      and occlusal conditions. However, the prevalence of bone change in the condyle
      correlated poorly with age, sex, and dental and occlusal condition with and
      without TMD.

PMID- 17449298
TI  - Consumption of areca quid, cigarettes, and alcohol related to the comorbidity of
      oral submucous fibrosis and oral cancer.
AB  - OBJECTIVE: Oral submucous fibrosis (OSF) is defined as a precancerous condition,
      and it is also commonly seen in clinical practice, coexisting with oral cancer.
      The aim of this study was to identify the effects of areca quid, cigarette, and
      alcohol on the coexistence of oral cancer and OSF. STUDY DESIGN: This is a case
      control study. One hundred four histologically confirmed male OSF subjects were
      included, which consisted of 65 OSF subjects without oral cancer (control group)
      and 39 OSF subjects with oral cancer (case group). RESULTS: The cigarette
      consumption in the case group was significantly higher than the control group. In
      drinking habits, the mean consumption of alcohol in the case group was
      significantly higher than the control group. Logistic regression analysis was
      used to identify these risk factors. Age and alcohol consumption showed a
      significant effect, and the odds ratios were 1.07 in age and 1.5 in alcohol
      consumption. CONCLUSION: Alcohol drinking could be a risk factor associated with
      an increased risk of malignant transformation and coexistence with oral cancer in
      OSF patients, but cigarette and areca quid were not risk factors in our study.
      For oral cancer prevention from OSF, more attention should be paid to the
      importance of public health strategies targeted toward preventing and reducing
      alcohol consumption.

PMID- 17449299
TI  - Unraveling the immune regulatory mechanisms imposed by Anaplasma.

PMID- 17449300
TI  - Ranavirus-associated mass mortality in imported red tailed knobby newts
      (Tylototriton kweichowensis): a case report.
AB  - A mass die-off of imported red tailed knobby newts (Tylototriton kweichowensis)
      occurred in 2004 in Belgium and the Netherlands. In addition to massive infection
      with Rhabdias tokyoensis, Ranavirus was isolated from three dead newts examined
      virologically and the gene coding for the major capsid protein of the virus was
      sequenced. The isolate showed 99.8% similarity to the published sequence of frog
      virus 3. Upon experimental infection of axolotls (Ambystoma mexicanum) with this
      isolate, no marked pathology was noticed and the virus could not be re-isolated
      at 9weeks post-inoculation. Apart from the possibility of exposure of a non
      sensitive host, the mortality episode in the newts may be related to stress
      resulting from the importation of the newts in breeding condition. This
      possibility is supported by the presence of degenerating egg-follicles in the
      females.

PMID- 17449301
TI  - Simultaneous application of the vascular endothelial growth factor (VEGF)
      receptor inhibitor PTK787/ZK 222584 and ionizing radiation does not further
      reduce the growth of canine oral melanoma xenografts in nude mice.
AB  - PTK787/ZK 222584 is an inhibitor of the vascular endothelial growth factor (VEGF)
      receptor tyrosine kinases. In this study, the effectiveness of PTK787/ZK 222584
      and radiation on canine oral melanoma xenografts was assessed. Xenografts were
      treated with radiotherapy (4x6Gy), or with PTK787/ZK 222584, or with a
      combination of both. Treatment efficacy was assessed using a tumour growth delay
      assay, serial power Doppler and pO(2) measurements during and after therapy.
      There was a significant growth delay for the group treated with radiation alone
      and for the combined treatment group. However, tumour growth delay was similar in
      both groups. Tumours were hypoxic before irradiation and no significant re
      oxygenation occurred during therapy. In all tumours, vascularity and perfusion
      were significantly lower at the end of the study but no significant differences
      in perfusion, vascularity and oxygenation status were observed between and within
      treatment groups. The combination of PTK787/ZK 222584 and radiotherapy did not
      perform better than radiotherapy alone in this model.

PMID- 17449302
TI  - Storage of equine red blood cells as a concentrate.
AB  - The study was undertaken to determine how equine red blood cells (RBCs) survive
      in storage bags designed for use with human RBCs. Separated RBCs were stored in a
      routine manner for 35 days and examined every 7 days for storage lesions.
      Measured parameters included haematology, haemolysis, pH, potassium, lactate,
      adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG). All tests were
      performed in vitro. Haematology did not change significantly. Haemolysis
      increased during storage but did not exceed human limits. pH and 2,3-DPG
      decreased, while lactate, potassium and ATP increased. RBCs deteriorated somewhat
      during storage, but when compared with human in vitro parameters, remained
      suitable for transfusion. It is concluded that equine erythrocytes can be stored
      for at least 35 days before transfusion.

PMID- 17449303
TI  - Digestive processes in ruminal drinkers characterized by means of the
      acetaminophen absorption test.
AB  - The aim of the present study was to measure transit patterns of nutrients and the
      absorptive ability in ruminal drinkers (RDs) compared with healthy unweaned
      calves. The acetaminophen (paracetamol) absorption test was used to characterize
      the oroduodenal transit rate. Clinical examination and the analysis of various
      blood parameters provided supplementary information on digestive processes. Three
      unweaned bucket-fed calves (one RD and two healthy controls) each from seven
      Swiss dairy farms were included in the study. Measurements (tests 1 and 2) were
      performed twice at an interval of 10 days. Between tests, the feeding technique
      of the RDs and one control calf per farm was changed to feeding with a nipple
      instead of by bucket (without nipple). Acetaminophen appearance in the blood was
      delayed and reduced in RDs compared with the controls. Acid-base metabolism and
      several haematological and metabolic parameters differed markedly between RDs and
      healthy controls. The characteristics of the oroduodenal transit rate, absorptive
      abilities and clinical status in RDs were nearly normalised within 10 days of
      reconditioning.

PMID- 17449304
TI  - Experimental animal infection models for Johne's disease, an infectious
      enteropathy caused by Mycobacterium avium subsp. paratuberculosis.
AB  - A critical literature review of experimental infection models for Johne's disease
      in farm and laboratory animals was conducted. A total of 73 references were
      admitted. They were published between 1938 and 2006 and covered species as
      diverse as cattle, sheep, goats, deer, mice, pigs and others. The factors that
      appeared to influence the outcome of experimental infections with Mycobacterium
      avium subsp. paratuberculosis (Mptb) were the species, breed and age of subject
      used for the infection, the route of infection, and the strain, dose and number
      of doses of Mptb used to inoculate the subjects. Natural paratuberculosis
      infection passes through stages, generally over a period measured in years.
      However, the endpoints chosen by researchers using experimental infections have
      been determined by the need for immunological, microbiological, pathological or
      clinical outcomes, and these were the likely factors determining the duration of
      the trials. Studies have been lacking in the use of a defined type strain of Mptb
      in pure culture prepared from an archived seed stock of Mptb that can be used at
      the same passage level in a later trial. Replication of experimental groups has
      been very uncommon, temporal replication equally rare, as have sufficiently long
      time scales so as to be able to observe a full range of immunological and
      pathological changes at different stages of the disease process. While it may be
      difficult to develop a satisfactory experimental infection model, there is room
      for improvement in the way experiments have been designed and carried out to
      date. Choice of animal species/breed of host and strain of Mptb used in an
      experimental model should be based on the purpose of the study (for example,
      vaccine efficacy trial, diagnostic test evaluation, pathogenesis study) and local
      needs. The strain of Mptb used should be typed using IS900 RFLP analysis, IS1311
      sequence analysis and other genotypic methods, and preferably be from an archived
      low passage pure culture with viable bacteria enumerated using a sensitive method
      rather than from an uncharacterised and unrepeatable tissue homogenate. It is
      generally agreed that the faecal-oral route is the most important natural route
      of exposure and the oral route is therefore the preferred route of experimental
      inoculation to achieve Johne's disease that closely resembles natural infection.

PMID- 17449305
TI  - Leptin inhibits mitogen-induced proliferation of peripheral T lymphocytes from
      Holstein cows.
AB  - This study examined the mitogenic response of bovine peripheral T lymphocytes to
      leptin, a pleiotropic hormone regulating food intake and energy expenditure.
      Leptin alone slightly suppressed proliferation of T lymphocytes in the presence
      of concanavalin A (ConA). Leptin also inhibited proliferation of T lymphocytes
      induced by anti-CD3 antibody. ConA treatment activated some protein kinases,
      including p44/p42(MAPK) and Akt/PKB, while anti-CD3 antibody treatment increased
      mRNA expression of suppressor of cytokine signalling (SOCS) 3, interferon
      (IFN)gamma, interleukin (IL) 2 and IL4 in T lymphocytes. Leptin alone increased
      only SOCS3 mRNA expression. Simultaneous treatment with mitogens and leptin
      enhanced IFNgamma mRNA expression but decreased IL2 mRNA expression, without any
      synergistic effect on phosphorylation of protein kinases or mRNA expression of
      SOCS3 and IL4. These results suggest that leptin modulates bovine T lymphocyte
      functions.

PMID- 17449306
TI  - Antihyperalgesic and analgesic properties of the N-methyl-D-aspartate (NMDA)
      receptor antagonist neramexane in a human surrogate model of neurogenic
      hyperalgesia.
AB  - NMDA-receptors are a major target in the prevention and treatment of hyperalgesic
      pain states in neuropathic pain. However, previous studies revealed equivocal
      results depending on study design and efficacy parameters. We tested the
      analgesic (generalized reduction of generation and processing of nociceptive
      signalling) and anti-hyperalgesic (prevention of central sensitization)
      properties of the NMDA-receptor antagonist neramexane and the potassium channel
      opener flupirtine in the intradermal capsaicin injection model. Furthermore, we
      tested the effect on pain summation (wind up). Eighteen healthy subjects received
      either a single dose of neramexane (40 mg p.o.), flupirtine (100 mg) or placebo
      in a double-blind, randomized, cross-over study. Pain evoked by intradermal
      capsaicin injection as well as pain evoked by pinpricks was significantly reduced
      by neramexane (-22% to -30% vs. placebo) in the non-sensitized skin indicating a
      marked analgesic effect. Moreover, dynamic mechanical allodynia (pain to light
      touch) was also significantly attenuated by neramexane (-28% vs. placebo).
      However, static secondary hyperalgesia to pinprick stimuli after capsaicin
      injection was not significantly reduced (-9% vs. placebo). Flupirtine showed no
      analgesic or anti-hyperalgesic effect. Mechanically-evoked wind up of pain
      sensation was not affected by any treatment. The results suggests that in a human
      surrogate model of neurogenic hyperalgesia a single low-dose of neramexane had a
      marked analgesic effect in the sensitized and in the non-sensitized state and
      thus may be a useful drug to treat the enhanced pain sensitivity in neuropathic
      pain patients. Its efficacy may be based on analgesia rather than anti
      hyperalgesia or anti-windup. In contrast, flupirtine showed neither an analgesic
      nor an anti-hyperalgesic effect at a dose used for the treatment of postoperative
      pain.

PMID- 17449307
TI  - Transient NOE-exchange-relay experiment: application to ligand-protein binding
      under slow exchange conditions.
AB  - A new version of one-dimensional (1)H experiment has been developed to probe
      ligand binding to macromolecular targets. The experiment, called transient NOE
      exchange relay, is similar to the 'reverse NOE pumping' technique [A. Chen, M.J.
      Shapiro, J. Am. Chem. Soc. 122 (2000) 414-415]. The T(2) filter is used to erase
      protein magnetization, and the saturation then spreads from protein to bound
      ligand (via NOE) and further to a free ligand (via on-off exchange). The ligand
      signals, monitored as a function of mixing time, present a familiar 'dip' pattern
      characteristic of transient NOE or transient exchange experiments. In addition to
      the T(2) filter, we have also implemented a T(1) filter which makes use of the
      fact that the selective T(1)(-1) rates in macromolecules are much higher than
      those in small ligands. To model the experiment, complete relaxation and exchange
      matrix analysis has been invoked. This formalism was further used as a starting
      point to develop a simplified treatment where the relaxation and exchange
      components are represented by 2x2 matrix and, in addition, there is a special
      term responsible for coupling of ligand magnetization to the protein spin bath.
      The proposed experimental scheme has been tested on a system of peanut agglutinin
      complexed with Me-beta-D-galactopyranoside, which is known to be in a slow
      exchange regime. The results suggest that the NOE-exchange-relay experiment can
      be used at the advanced stages of the drug development process to confirm high
      affinity ligand binding.

PMID- 17449308
TI  - The mandibular cortex on radiographs as a tool for osteoporosis risk assessment:
      the OSTEODENT Project.
AB  - The aim of this study was to measure the accuracy of porosity of the mandibular
      cortex on dental panoramic radiographs (DPRs) in diagnosis of osteoporosis, alone
      and in combination with a clinical risk index. Six hundred seventy-one women (45
      70yr) were recruited in the study, and dual-energy X-ray absorptiometry of the
      hip and lumbar spine was performed. A clinical index of osteoporosis risk
      (OSIRIS) and a DPR were obtained for each subject. The cortical appearance on the
      DPR was classified using the mandibular cortical index (MCI) by 5 observers.
      receiver operating characteristic (ROC) curve analysis was performed with
      calculation of area under the ROC curve (AUC) and sensitivity and specificity at
      various thresholds. Complete data were available for 653 subjects, of whom 21.6%
      had osteoporosis. The AUC for OSIRIS was 0.838. When used alone as the diagnostic
      test, MCI AUC for the 5 observers ranged from 0.560 to 0.670, significantly less
      than OSIRIS. Intraobserver and interobserver repeatability of MCI assessment was
      inconsistent. We conclude that MCI has limited value for osteoporosis diagnosis,
      being most appropriate as a method of fortuitous case-finding.

PMID- 17449309
TI  - Vitellogenin gene expression and hemolymph vitellogenin during vitellogenesis,
      final maturation, and oviposition in female kuruma prawn, Marsupenaeus japonicus.
AB  - In penaeid shrimps, vitellogenin (VTG), the precursor of vitellin, is synthesized
      in the ovary and hepatopancreas and accumulated in oocytes during ovarian
      development. In the present study, VTG gene expression levels and hemolymph VTG
      levels were determined throughout ovarian development in female kuruma prawn,
      Marsupenaeus japonicus. Hemolymph VTG levels and VTG mRNA levels in the ovary and
      hepatopancreas were high during vitellogenesis, remained high until final
      maturation, and then decreased after oviposition. This profile suggests that VTG
      synthesis activity increases during vitellogenesis and decreases after
      oviposition. Absence of a significant increase in ovary size in final maturation
      suggests cessation of yolk accumulation and low activity of VTG synthesis in
      spite of high VTG mRNA levels. VTG mRNA levels in ovary and hepatopancreas were
      both highly correlated during vitellogenesis. Thus, their contribution to yolk
      accumulation seems to be similar. In contrast, VTG mRNA levels in the
      hepatopancreas increased more slowly at the start of vitellogenesis and declined
      more sharply after oviposition than in the ovary. This suggests a difference in
      the regulation of VTG synthesis between the ovary and the hepatopancreas.

PMID- 17449310
TI  - Sugar digestion in mosquitoes: identification and characterization of three
      midgut alpha-glucosidases of the neo-tropical malaria vector Anopheles aquasalis
      (Diptera: Culicidae).
AB  - Dietary carbohydrates provide an important source of energy for flight, and
      contribute to longevity and fecundity of mosquitoes. The most common sugar
      mosquitoes ingest is sucrose, and digestion of this substance is carried out
      mainly by alpha-glucosidases. In the current work, we tested the efficiency of
      sucrose on Anopheles aquasalis female diet. The best longevity (days) was reached
      when sugar was available in the diet, whereas most only blood fed females were
      dead 6 days after emergence. Three alpha-glucosidase isoforms were detected in
      the adult female midgut, named alphaGlu1, alphaGlu2 and alphaGlu3. These are
      acidic alpha-glucosidases with optima pH around pH 5.5. alphaGlu1 and alphaGlu2
      are present in both secreted and membrane-bound forms, whereas alpha-Glu3 only in
      anchored to membranes. The alpha-glucosidase activity is concentrated mainly in
      the posterior midgut (70%), both in non-fed or 10% sucrose fed females. The
      single form of these alpha-glucosidases seemed to be approximately 70 kDa
      polypeptides, although alphaGlu2 is presented in >or=600 kDa self-aggregates. Km
      values of alphaGlu1, alphaGlu2 and alphaGlu3 differed significantly from each
      other, supporting the statement that three alpha-glucosidases are produced in the
      female midgut. Together, all data suggest that sugar is an essential component of
      A. aquasalis female diet. In addition, alpha-glucosidases are synthesized in the
      same place where sucrose is digested and absorbed, the midgut.

PMID- 17449311
TI  - Cloning and characterization of insect arylalkylamine N-acetyltransferase from
      Bombyx mori.
AB  - Arylalkylamine N-acetyltransferase (AANAT) catalyzes N-acetylation of
      arylarkylamines. A cDNA of Bombyx mori insect AANAT (Bm-iAANAT) was found by
      searching an expressed-sequence tag (EST) database of B. mori (SilkBase). The
      cDNA encoded a 261 amino acid protein. The mRNA of Bm-iAANAT was expressed in
      eggs, larvae, adults and various tissues. Recombinant Bm-iAANAT protein was
      expressed in Sf9 cells by a baculovirus expression system. The AANAT activity of
      Bm-iAANAT was inhibited by high concentrations (over 0.01 mM) of tryptamine used
      as a substrate. The Bm-iAANAT acetylated tryptamine, serotonin, dopamine,
      octopamine, tyramine and norepinephrine. This is the first report of a cloned
      AANAT that acetylated norepinephrine. These results suggest that Bm-iAANAT is a
      novel member of insect AANAT family with unique kinetic properties and a broad
      substrate range.

PMID- 17449312
TI  - Molecular characteristics and expression analysis of calreticulin in Chinese
      shrimp Fenneropenaeus chinensis.
AB  - Calreticulin (CRT), as an endoplasmic reticulum luminal resident protein, plays
      important roles in Ca(2+) homeostasis and molecular chaperoning. CRT on the
      surface of the cell can modulate cell adhesion, phagocytosis and integrin
      dependent Ca(2+) signaling. The full length cDNA of calreticulin (FcCRT) was
      cloned from Chinese shrimp Fenneropenaeus chinensis. It consists of 1672 bp with
      an open reading frame of 1221 bp, encoding 406 amino acids. This is the first
      reported cDNA sequence of calreticulin in Crustacea. The deduced amino acid
      sequence of FcCRT showed high identity with those of Bombyx mori (88%),
      Drosophila melanogaster (83%), Mus musculus (82%) and Homo sapiens (82%). Highest
      expression of FcCRT was detected in ovary by Northern blot and in situ
      hybridization. Different mRNA levels of FcCRT were detected at various molting
      stages. Expression of FcCRT was induced significantly after 3 h of heat shock
      treatment, reached the maximum at 4 h and dropped after that. Differential
      expression profiles of FcCRT were observed in hepatopancreas and haemocytes when
      shrimp were challenged by white spot syndrome virus (WSSV). From the above
      results, we inferred that FcCRT might play important roles in Ca(2+) homeostasis,
      chaperoning and immune function in shrimp.

PMID- 17449313
TI  - Time trends and risk factors for diabetes mellitus in cats presented to
      veterinary teaching hospitals.
AB  - Veterinary Medical Data Base records of cats with diabetes mellitus (DM) from
      1970 through 1999 were reviewed to identify trends in hospital prevalence of DM
      and potential host risk factors. Hospital prevalence increased from eight cases
      per 10,000 in 1970 to 124 per 10,000 in 1999 (P < 0.001). Case fatality percent
      at first visit decreased from 40% to 10% (P < 0.001). Hospital prevalence
      increased in all age groups (P < 0.002). There was no apparent seasonal pattern
      in hospital prevalence. Significant risk factors included male gender, increasing
      age for both genders (P < 0.001), increasing weight for males (P < 0.001), and
      mixed vs pure breed for females (P = 0.006).

PMID- 17449314
TI  - Successful treatment of cervical spinal epidural empyema secondary to grass awn
      migration in a cat.
AB  - Spinal epidural empyema (SEE) represents a severe pyogenic infection of the
      epidural space. Clinical signs of the disease are non-specific--increased body
      temperature, intense neck pain, neurological signs of a transverse myelopathy-
      and can lead to severe and permanent neurological deficits. This report describes
      the diagnosis and successful surgical treatment of cervical SEE secondary to
      grass awn migration in a cat. Although it is uncommon, this disease should be
      suspected in cats with progressive myelopathy. Early diagnosis and emergency
      surgery combined with antibiotic therapy are required to allow a complete
      recovery.

PMID- 17449315
TI  - Disturbed intracortical excitability in early Parkinson's disease is l-DOPA dose
      related: a prospective 12-month paired TMS study.
AB  - We were interested to know if chronic l-DOPA treatment in Parkinson's disease
      (PD) patients could restore impairment of the intracortical excitability, when
      this difference could occur, and if it was related to the total daily dose of l
      DOPA. Twelve patients with early PD were studied using paired transcranial
      magnetic stimulation before the administration of l-DOPA, and then after 3, 6,
      and 12 months of l-DOPA treatment. The level of disturbed intracortical
      excitability strongly correlated with the total daily dose of l-DOPA. The level
      of cortical excitability in PD patients seems to be indirectly related to the
      nigro-striatal functioning.

PMID- 17449316
TI  - Interest in predictive testing for Parkinson's disease: impact of neuroprotective
      therapy.
AB  - As predictive testing for Parkinson's disease (PD) becomes available, it will be
      important to understand in whom such testing will be used. To address this issue,
      we conducted a mail survey of 138 first-degree relatives of PD patients. In the
      absence of treatment, 60% reported that they would either "definitely" or
      "probably" be interested in predictive testing. In the setting of a clinical
      trial, this number increased to 71% (p=0.04) and when neuroprotective therapy is
      available, interest increased to 90% (p<0.001). Interest in predictive testing
      for PD is moderate in the absence of effective therapy, and goes up significantly
      when both clinical trial participation and neuroprotective therapy are offered.

PMID- 17449317
TI  - Role of secreted glyceraldehyde-3-phosphate dehydrogenase in the infection
      mechanism of enterohemorrhagic and enteropathogenic Escherichia coli: interaction
      of the extracellular enzyme with human plasminogen and fibrinogen.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.12) is an anchorless,
      multifunctional protein displayed on the surface of several fungi and Gram
      positive pathogens, which contributes to their adhesion and virulence. To date a
      role for extracellular GAPDH in the pathogenesis of Gram-negative bacteria has
      not been described. The aim of this study was to analyze the extracellular
      localization of GAPDH in enterohemorrhagic (EHEC) and enteropathogenic (EPEC)
      Escherichia coli strains and to examine its interaction with host components that
      could be related to the infection mechanism. Recombinant E. coli GAPDH was
      purified and polyclonal antibodies were obtained. Western blotting and
      immunoelectron microscopy showed that GAPDH is located on the bacterial surface
      and released to the culture medium of EHEC and EPEC strains. GAPDH export in
      these Gram-negative pathogens depends on the external medium, is not mediated by
      vesicles and leads to an extracellular active enzyme. Non-pathogenic E. coli
      strains do not secrete GAPDH. Two-dimensional electrophoresis analysis showed
      that in E. coli GAPDH is present at least in two major forms with different
      isoelectric points. Of these forms, the more basic is secreted. Purified GAPDH
      was found to bind human plasminogen and fibrinogen in Far-Western blot and ELISA
      based assays. In addition, GAPDH remained associated with colonic Caco-2
      epithelial cells after adhesion of EHEC or EPEC. These observations indicate that
      exported GAPDH may act as a virulence factor which could contribute to EHEC and
      EPEC pathogenesis. This is the first description of an extracellular localization
      for this enzyme, with a function other than its glycolytic role in Gram-negative
      pathogens.

PMID- 17449318
TI  - Evaluation of an in-house genotyping resistance test for HIV-1 drug resistance
      interpretation and genotyping.
AB  - INTRODUCTION: The human immunodeficiency virus type 1 (HIV-1) genotyping
      resistance test (GRT) has been considered essential for HIV-1 drug resistance
      monitoring. However, it is not commonly used in some developing countries in Asia
      and Africa due to its high running cost. OBJECTIVE: This study aims to evaluate a
      new low-cost in-house GRT for both subtype B and non-B HIV-1. STUDY DESIGN: The
      in-house GRT sequenced the entire protease and 410 codons of reverse
      transcriptase (RT) in the pol gene. Its performance on drug resistance
      interpretation was evaluated against the FDA-approved ViroSeq HIV-1 Genotyping
      System. Particularly, a panel of 235 plasma samples from 205 HIV-1-infected
      patients in Hong Kong was investigated. The HIV-1 drug resistance-related
      mutations detected by the two systems were compared. The HIV-1 subtypes were
      analyzed through the REGA HIV-1 Genotyping Tool and env phylogenetic analysis.
      RESULTS: Among the 235 samples, 229 (97.4%) were successfully amplified by both
      in-house and ViroSeq systems. All PCR-negative samples harbored viral RNA at <400
      copies/mL. The in-house and ViroSeq system showed identical drug resistance
      related mutation patterns in 216 out of 229 samples (94.3%). The REGA pol
      genotyping results showed 93.9% (215/229) concordance with the env phylogenetic
      results including HIV-1 subtype A1, B, C, D, G, CRF01_AE, CRF02_AG, CRF06_cpx,
      CRF07_BC, CRF08_BC, CRF15_01B and other recombinant strains. The cost of running
      the in-house GRT is only 25% of that for the commercial system, thus making it
      suitable for the developing countries in Asia and Africa. CONCLUSIONS: Overall,
      our in-house GRT provided comparable results to those of the commercial ViroSeq
      genotyping system on diversified HIV-1 subtypes at a more affordable price which
      make it suitable for HIV-1 monitoring in developing countries.

PMID- 17449319
TI  - Effects of remote muscle contraction on transcranial magnetic stimulation-induced
      motor evoked potentials and silent periods in humans.
AB  - OBJECTIVE: To determine to what extent tonic contraction of the testing muscle
      modulates the effect of remote muscle contraction on motor evoked potentials
      (MEPs) and cortical silent periods (CSPs) in resting and active proximal and
      distal muscles following transcranial magnetic stimulation (TMS). In addition, we
      tested whether the remote effect on MEP was observable when the test MEP was
      small. METHODS: While performing tonic abductions of the first dorsal
      interosseous (FDI), flexor carpi radialis, or anterior deltoid muscles, subjects
      made phasic dorsiflexions of the right ankle at various forces. MEPs and CSPs
      were induced by separately optimized TMS intensities and locations in the left
      motor cortex and recorded electromyographically. RESULTS: Phasic dorsiflexion
      increased MEP amplitude and shortened CSP duration in a dorsiflexion intensity
      dependent manner in all muscles tested. At test MEPs <10% of Mmax, remote effects
      on MEP amplitude and CSP duration were significantly attenuated while the testing
      muscle was active. CONCLUSIONS: Phasic contraction of remote muscles potentiates
      excitatory- and suppresses inhibitory intracortical neuronal pathways converging
      on corticospinal tract cells innervating the upper limb muscles even when they
      are active. However, the magnitude of the remote effect on MEP amplitude strongly
      depends on the test MEP amplitude. SIGNIFICANCE: Although remote effects on MEP
      amplitude and CSP duration are observed even when the test muscle is active, the
      magnitude of the remote effect strongly depends on TMS intensity.

PMID- 17449320
TI  - fMRI of peripheral visual field representation.
AB  - OBJECTIVE: Despite mapping tools for central visual field, delineation of
      peripheral visual field representations in the human cortex has remained a
      challenge. Access to large visual field and differentiation of retinotopic areas
      with robust mapping procedures and automated analysis are beneficial in basic
      research and could accelerate development of clinical applications. METHODS: We
      constructed a simple optical near view system for wide visual field stimulation,
      and examined the topology of retinotopic areas. We used multifocal (mf) design,
      which enables analysis with general linear model and standard fMRI softwares and
      is easily automated. RESULTS: Our stimulation method enabled individual mapping
      of visual field up to 50 degrees of eccentricity and showed that retinotopic
      visual areas extended through posterior cerebrum. In addition, we located a
      separate peripheral upper visual field representation in parieto-occipital (PO)
      sulcus. CONCLUSIONS: These functional results are in line with earlier
      histological data, and support recent findings on human V6, a retinotopic area in
      the medial PO sulcus with an apparent emphasis on peripheral visual field.
      SIGNIFICANCE: Our projection system and mf-design together enable efficient and
      robust retinotopic mapping of wide visual field, which can at low cost be adapted
      to any clinical environment with visual back-projection system.

PMID- 17449321
TI  - Cardiology at Westmead Hospital 1978-1990.
AB  - The development of the cardiology unit at Westmead Hospital occurred
      simultaneously with major advances in cardiology. Being the only teaching
      hospital built in New South Wales in the twentieth century, the hospital opened
      on 10 November 1978 on the site of the old Parramatta speedway. John Uther
      commenced in April 1979 and the electrophysiology laboratory opened in June,
      beginning an era of research and arrhythmia management that lead to the unit
      being a centre of excellence for arrhythmias. Cardiac surgery commenced in
      November 1981 with David Johnson as the initial surgeon, developing
      electrophysiological surgery. At the same time, Andreas Gruntzig was pioneering
      coronary angioplasty and this service commenced at Westmead in 1983. The early
      electrophysiology research culminated in the Ralph Reader prize being awarded to
      three Westmead fellows, David Richards, Robert Denniss and Lorraine Holley over
      the first three years with Mark Cooper awarded in 1986. Also in 1986, the era of
      thrombolytic therapy commenced for acute myocardial infarction. Dr Michel
      Mirowski implanted the first defibrillator in 1980 with approval by the FDA in
      1985. Telectronics developed the first Australian defibrillator with considerable
      input from the unit, resulting in the first Australian made defibrillator
      inserted by the unit in 1987. The staffing at the unit has been a combination of
      staff specialists and visiting medical officers who have worked in all invasive
      and non invasive laboratories. This resulted in a unique and successful concept
      with the VMOs also attending the peripheral hospitals of the area resulting in
      the first successful example of clinical networking throughout the area. This has
      resulted in a full range of cardiac services available to all patients in all
      hospitals of the area.

PMID- 17449322
TI  - Cardiopulmonary bypass to facilitate excision of a giant pleural tumour.
AB  - A 55-year-old female developed dyspnoea following an elective hysteroscopy. A
      chest radiograph demonstrated a tissue density opacity occupying the right
      hemithorax. A CT scan suggested this was a tumour arising from the postero
      lateral chest wall. Surgical resection was attempted; however, mobilisation of
      the tumour caused significant airway compromise. Cardiopulmonary bypass was used
      to facilitate oxygenation while the tumour was dissected and removed. Although
      cardiopulmonary bypass has been used as an adjunct to aid resection of tumours
      invading major vascular or upper airway structures, in this case CPB was used to
      aid mobilisation of a giant pleural tumour.

PMID- 17449323
TI  - Vitamin D receptor gene polymorphisms and sputum conversion time in pulmonary
      tuberculosis patients.
AB  - A cohort of pulmonary tuberculosis (TB) patients in a South African admixed
      population was investigated to determine if the vitamin D receptor gene (VDR)
      polymorphisms FokI, ApaI, and TaqI are associated with TB susceptibility or time
      to sputum conversion, and to investigate other clinical and demographic factors
      affecting the rate of response to treatment. Firstly, a case-control association
      study of 249 TB cases and 352 healthy controls was carried out to investigate
      association of VDR polymorphisms with TB susceptibility. Secondly, a cohort of
      pulmonary tuberculosis patients with conversion times for both sputum smear
      (n=220) and culture (n=222) were analysed to determine factors contributing to
      mycobacterial resolution in sputum. Age and gender adjusted Cox regression models
      were constructed. Our results indicate that the extent of disease at diagnosis
      was predictive of both smear and culture conversion times in the final models.
      Smoking status and VDR genotype contributed independently to smear conversion
      time, with ApaI 'AA' genotype and TaqI 'T'-containing genotypes predictive of a
      faster response to TB chemotherapy. We did not find an association between VDR
      genotype and TB in the case-control study. We conclude that the time taken for an
      individual to convert to sputum negativity while on antituberculosis therapy can
      be independently predicted by the VDR genotype.

PMID- 17449324
TI  - Perceived disability and lifestyle modification following hospitalization for non
      ST elevation versus ST elevation acute coronary syndromes: the patients' point of
      view.
AB  - BACKGROUND AND AIMS: Medical personnel generally believe that non-ST elevation
      (NSTE) acute coronary syndromes (ACS) are less damaging than ST elevation
      myocardial infarction (STEMI), in keeping with the lower morbidity and mortality
      attributed to these subgroups in randomized clinical trials. We examined whether
      this concept translates into a difference from the patients' point of view
      regarding lifestyle modification and return to work following hospitalization for
      ACS. METHODS: A structured anonymous self-completed questionnaire was mailed and
      returned by 160 consecutive patients (age 64+/-11 years; 125 (78%) men) 3-12
      months after hospitalization for ACS. In 49 patients, the diagnosis was unstable
      angina pectoris (UAP), in 34 non-ST elevation myocardial infarction (NSTEMI) and
      in 73, ST elevation myocardial infarction (STEMI). The questionnaire addressed
      issues relating to demographic data, medical history, occupation, employment and
      income before the acute event, changes following hospitalization for ACS and
      questions relating to current perceived health status and return to work.
      RESULTS: Most (98/159, 62%) patients saw themselves as "heart patients" after
      hospitalization for ACS. Quality of life was perceived to have decreased in 70
      (44%), self-image in 85 (53%), self-confidence in 78 (49%) and sexual function in
      75 (48%), with no differences according to ACS type. Anxiety was reported by 85
      (54%) patients and anxiety level (1.47+/-1.25 on the Brief Symptom Inventory
      scale) was high. Only 38 (49%) of 77 patients who were working prior to the acute
      event returned to full- or part-time gainful employment. By multivariate
      analysis, return to work was associated with 3 variables: younger age (p=0.015),
      shorter duration of hospitalization (p=0.036) and higher income bracket prior to
      the acute event (p=0.0001), with no relation to gender, in-hospitalization
      revascularization strategy, rehabilitation program or to underlying cardiac
      diagnosis (UAP, NSTEMI or STEMI). CONCLUSIONS: Hospitalization for ACS had a
      major negative impact on patient lifestyle and return to work, irrespective of
      the underlying cardiac diagnosis. The experience of hospitalization for an acute
      heart condition was uniformly traumatic with in many instances a prolonged
      adverse effect on patient function.

PMID- 17449325
TI  - Common human Toll-like receptor 4 polymorphisms--role in susceptibility to
      respiratory syncytial virus infection and functional immunological relevance.
AB  - Evidence suggests that Toll-like receptor 4 (TLR4) contributes to immune
      recognition of respiratory syncytial virus (RSV). The TLR4 gene harbours a
      polymorphism-Asp299Gly-previously associated with reduced TLR4 signalling. To
      understand of how host genetic variation influences the outcome of RSV infection
      in children, we examined the association between the TLR4 299Gly allele and
      severe RSV disease. By genotyping 236 children with RSV infection and 219 healthy
      controls we found no association between the risk of severe RSV infection and
      Asp299Gly polymorphisms (P>0.05), and we demonstrate that the TLR4 Asp299Gly
      genotype does not influence susceptibility to either RSV serotype A or B
      (P>0.05). Finally, examining the functional impact of the TLR4 Asp299Gly
      polymorphism (n=58), we demonstrate that proinflammatory cytokine production
      following TLR4 activation was indistinguishable between homozygous (Asp/Asp) and
      heterozygous (Asp/Gly) subjects. We conclude that the Asp299Gly TLR4 polymorphism
      does not alter receptor function and does not influence the risk of severe RSV
      infection.

PMID- 17449326
TI  - In vitro, ex vivo and in vivo immunopharmacological activities of the isoxazoline
      compound VGX-1027: modulation of cytokine synthesis and prevention of both organ
      specific and systemic autoimmune diseases in murine models.
AB  - We have presently studied the in vitro, ex vivo and in vivo immunopharmacological
      effects of VGX-1027 [(S,R)-3-phenyl-4,5-dihydro-5-isoxasole acetic acid]. This
      compound reduced the secretion of IL-1beta, TNF-alpha and IL-10 from purified
      murine macrophages stimulated "in vitro" with lipopolysaccharide (LPS), and it
      also modified the signaling pathways induced in these cells by LPS entailing
      reduced activation of NF-kappaB and p38 MAP kinase pathways along with up
      regulation of ERK pathways. VGX-1027 appeared to spare T cell function as it was
      unable to modify the proliferation and/or secretion of IL-2, IFN-gamma and IL-4
      induced in purified murine CD4+ T cells from stimulation with either CD3+CD28 or
      ConA. These effects on macrophages may account for the capacity of VGX-1027 to
      markedly ameliorate the course of both acute and chronic immunoinflammatory
      diseases in mice such as carrageenan-induced pleurisy, LPS-induced lethality and
      type II collagen-induced arthritis. Acute and subacute toxicological studies show
      that the drug is not toxic at the doses that exert biological effects in these
      preclinical models. These data warrant additional studies for the potential use
      of VGX-1027 in the clinical setting.

PMID- 17449327
TI  - Secretory immunoglobulin A (sIgA) deficiency in serum of patients with GALTectomy
      (appendectomy and tonsillectomy).
AB  - INTRODUCTION: In adult human beings, 80-85% of the immune cells are located in
      the digestive tract mucosa; hence the importance of the Gut Associated Lymphoid
      Tissue (GALT) in host defence. We studied the influence of the surgical removal
      of two important parts of the gut associated with lymphoid tissue (tonsillectomy
      and appendectomy) on immune parameters. METHODS: One hundred and sixty patients
      were enrolled in this study. They were divided into four groups of forty patients
      each and matched for gender and age: group 1, appendectomized and
      tonsillectomized; group 2, only appendectomized; group 3, only tonsillectomized;
      and group 4, control group, neither tonsillectomized nor appendectomized. We
      analysed in blood: hemogram, protein electrophoresis, lymphocytic populations (T4
      cells, T8 cells, NK cells), IgG, IgM, IgA immunoglobulin, and their fractions
      IgA1, IgA2, and secretory IgA. RESULTS: Levels of secretory IgA in serum of
      patients in group 1 were significantly lower than in the other three groups (1.89
      mg/dl, group 1; 2.32 mg/dl, group 2; 2.19 mg/dl, group 3 and 4.97 mg/dl, group 4;
      p<0.0001). Also, the values found in the two groups that had undergone only one
      of the operations were clearly lower than in control patients (p<0.0001). In this
      study, the reduction was sustained for a period of between 3 months and 3 years
      in appendectomized patients, and more than 20 years in tonsillectomized patients.
      IN SUMMARY: GALTectomy (appendectomy and tonsillectomy) significantly decreases
      secretory IgA levels in serum. The decrease is more intense when both operations
      have been done.

PMID- 17449328
TI  - Radiation-induced apoptosis along with local and systemic cytokine elaboration is
      associated with DC plus radiotherapy-mediated renal cell tumor regression.
AB  - Utilizing melanoma and sarcoma tumor models syngeneic to C57BL/6 mice, we
      previously reported the antitumor effects of intratumoral (i.t.) administration
      of dendritic cells (DC) combined with localized radiotherapy (RT). However, the
      mechanisms underlying the augmented therapeutic effects have yet to be fully
      defined. Using the BALB/c host, we explored in this study the capacity of RT to
      augment the therapeutic efficacy of DC in the syngeneic renal cell cancer, Renca.
      I.t. DC administration combined with RT inhibited tumor growth in a synergistic
      manner. This extends our previous findings using a different host strain and two
      histologically distinct tumor models. More importantly, we provide evidence in
      this report that RT induced significant apoptosis and necrosis in Renca tumor
      cells, which involved down-regulated expression of Bcl-2 and a concurrent up
      regulated expression of Bax. We also found significantly elevated expression of
      TNFalpha in RT plus DC-treated Renca tumors. Furthermore, splenocytes isolated
      from DC plus RT-treated mice elaborated higher levels of IL-2, IL-4, IFNgamma and
      IgG, IgM in response to tumor cells compared with splenocytes from monotherapy
      treated hosts. These data support the conclusion that radiotherapy enhanced DC
      vaccination by inducing tumor cell apoptosis in BABL/c host, and the
      significantly augmented therapeutic efficacy by RT+DC treatment was associated
      with an increased local production of TNFalpha as well as an amplified systemic
      antitumor responses conferred by the combined therapy. I.t. DC administration in
      concert with localized RT may represent a promising novel regimen for human
      cancer therapy.

PMID- 17449329
TI  - Serum surfactant protein D is correlated to development of dementia and augmented
      mortality.
AB  - Development of dementia, including Alzheimer's disease (AD), is associated with
      lipid dysregulation and inflammation. As the host defense lectin surfactant
      protein D (SP-D) has multiple effects in lipid homeostasis and inflammation, the
      correlation between SP-D concentrations and development of dementia was
      investigated. A total of 418 non-demented persons were included in the study and
      cognitively re-examined after 3 years, while survival was followed for 11 years.
      Serum SP-D concentrations were measured at baseline. Logistic regression analysis
      controlling for age, gender, smoking status, and CRP showed that Odds Ratio for
      developing dementia was 2.62 (1.12-6.15) with an SP-D concentration in the
      highest quartile compared to the other quartiles. The risk of AD was 2.55 (0.95
      6.90). Cox regression controlling for the same variables showed that hazard ratio
      of death was 1.43 (1.06-1.92) in the highest quartile. SP-D concentration thus
      correlates to development of dementia as well as to augmented mortality.

PMID- 17449330
TI  - Tryptase haplotype in mastocytosis: relationship to disease variant and
      diagnostic utility of total tryptase levels.
AB  - Serum mast cell tryptase levels are used as a diagnostic criterion and surrogate
      marker of disease severity in mastocytosis. Approximately 29% of the healthy
      population lacks alpha tryptase genes; however, it is not known whether lack of
      alpha tryptase genes leads to variability in tryptase levels or impacts on
      disease severity in mastocytosis. We have thus analyzed tryptase haplotype in
      patients with mastocytosis, computing correlations between haplotype and plasma
      total and mature tryptase levels; and disease category. We found: (1) the
      distribution of tryptase haplotype in patients with mastocytosis appeared
      consistent with Hardy-Weinberg equilibrium and the distribution in the general
      population; (2) the disease severity and plasma tryptase levels were not affected
      by the number of alpha or beta tryptase alleles in this study; and (3)
      information about the tryptase haplotype did not provide any prognostic value
      about the severity of disease. Total and mature tryptase levels positively
      correlated with disease severity, as well as prothrombin time and partial
      thromboplastin time, and negatively correlated with the hemoglobin concentration.

PMID- 17449331
TI  - Evaluation of an epilepsy education program for Grade 5 students: a cluster
      randomized trial.
AB  - OBJECTIVE: Epilepsy is a common and often highly stigmatized disorder. Several
      international organizations indicate a need to assess the stigma that exists and
      to develop and evaluate interventions to dispel myths about epilepsy. METHODS: A
      stratified cluster randomized controlled trial evaluated whether an epilepsy
      education program (intervention) increases knowledge of and positive attitudes
      about epilepsy in Grade 5 students (ages 9-11). The study also investigated
      characteristics of the individuals (gender, language spoken at home, familiarity
      with epilepsy) and schools (Catholic vs public, size of school, and school level
      socioeconomic status) that affect epilepsy knowledge and attitudes. We assessed
      epilepsy knowledge and attitudes at baseline and 1 month following the program
      using a 33-item questionnaire. RESULTS: In total, 24 schools (783 individuals)
      were cluster randomized. Those in the intervention group had an average 11.8
      point increase (95% confidence interval (CI)=11.4-12.5) in knowledge 1 month
      following the program, compared with the control group increase of 2.2 points
      (95% CI=1.8-2.6) out of a total of 57 points. For attitudes, the intervention
      group had a mean increase of 8.15 points (95% CI=4.70-11.60), compared with the
      control group increase of 1.64 points (95% CI=-0.84-4.42) out of a total of 50
      points. The intervention was responsible for 63% of the variation in postprogram
      epilepsy knowledge and 28% of the variation in postprogram attitudes about
      epilepsy. CONCLUSIONS: The epilepsy education program was associated with a
      significant increase in epilepsy knowledge and positive attitudes in the
      intervention group 1 month later compared with the control group.

PMID- 17449332
TI  - Drop-out rates of cancer patients participating in longitudinal RCTs.

PMID- 17449333
TI  - RedHot.

PMID- 17449334
TI  - Letter to the Editor re Yu and Holmgren. Traditional endpoint of progression-free
      survival (PFS) may not be appropriate for evaluating cytostatic agents combined
      with chemotherapy in cancer clinical trials.

PMID- 17449335
TI  - Mitochondrial targeting of quinones: therapeutic implications.
AB  - Mitochondrial oxidative damage contributes to a range of degenerative diseases.
      Ubiquinones have been shown to protect mitochondria from oxidative damage, but
      only a small proportion of externally administered ubiquinone is taken up by
      mitochondria. Conjugation of the lipophilic triphenylphosphonium cation to a
      ubiquinone moiety has produced a compound, MitoQ, which accumulates selectively
      into mitochondria. MitoQ passes easily through all biological membranes and,
      because of its positive charge, is accumulated several hundred-fold within
      mitochondria driven by the mitochondrial membrane potential. MitoQ protects
      mitochondria against oxidative damage in vitro and following oral delivery, and
      may therefore form the basis for mitochondria-protective therapies.

PMID- 17449336
TI  - The role of hemoglobin oxygen affinity in oxygen transport at high altitude.
AB  - Hemoglobin is involved in the regulation of O(2) transport in two ways: a long
      term adjustment in red cell mass is mediated by erythropoietin (EPO), a response
      to renal oxgyenation. Short-term, rapid-response adjustments are mediated by
      ventilation, cardiac output, hemoglobin oxygen affinity (P50), barriers to O(2)
      diffusion, and the control of local microvascular tissue perfusion. The
      distribution of O(2) between dissolved (PO2) and hemoglobin-bound (saturation) is
      the familiar oxygen equilibrium curve, whose position is noted as P50. Human
      hemoglobin is not genetically adapted for function at high altitude. However,
      more specialized species native to high altitudes (guinea pig and bar-headed
      goose, for example) seem to have a lower P50 than their sea level counterparts,
      an adaptation that presumably promotes O(2) uptake from a hypoxic environment.
      Humans, native to very high altitude either in the Andes or Himalayan mountains,
      also can increase O(2) affinity, not because of a fundamental difference in
      hemoglobin structure or function, but because of extreme hyperventilation and
      alkalosis.

PMID- 17449337
TI  - High performance liquid chromatography with ultraviolet detection for the
      determination of SYUIQ-5, a novel telomerase inhibitor for cancer therapy:
      application to an enzyme kinetic study in rat liver microsomes.
AB  - A sensitive assay for the determination of SYUIQ-5, a novel telomerase inhibitor
      and anti-tumor drug, in rat liver microsomes was developed by using high
      performance liquid chromatography with ultraviolet detection. SYUIQ-5 was
      incubated in vitro with liver microsomes from rats pre-treated with control
      vehicle, beta-naphthofIavone, phenobarbital, 20% ethanol or dexamethasone. The
      analytes were extracted with diethyl ether and separated a C(18) 5-microm
      analytical column. Elution was conducted with 30 mM dipotassium hydrogen
      phosphate (pH 8.0)-methanol-triethylamine (30:70:0.05, v/v/v) at a flow-rate of
      1.0 ml/min and the detection of UV absorbance was conducted at 278 nm. Intra-day
      and inter-day precision and accuracy of the method were within 10%. The mean
      analytical recoveries of SYUIQ-5 ranged from 78.8 to 95.3%. The linearity of the
      calibration curve was in the range of 1.0-80.0 microM. The lower limit of
      quantification (LOQ) was 1.0 microM. Kinetic analysis showed that beta
      naphthofIavone and dexamethasone significantly induced SYUIQ-5 metabolism,
      suggesting that cytochrome P450 1A and 3A are the major contributor to SYUIQ-5
      metabolism in rat liver microsomes.

PMID- 17449338
TI  - Micronutrient deficiency and the prevalence of mothers' overweight/obesity in
      Egypt.
AB  - I examine the relationship between micronutrient deficiency and the prevalence of
      mothers' overweight/obesity in Egypt using the 1997 Egyptian Integrated Household
      Survey. The ordered logit results show an overlap between micronutrient
      deficiency and the prevalence of mothers' overweight/obesity in Egypt. The odds
      of being overweight/obese are 80.8% higher for micronutrient deficient mothers
      than for non-deficient mothers, keeping all other variables constant. These
      results have at least two interesting policy implications. First, as the
      potential impact of the interaction between micronutrient deficiency and chronic
      diseases is not well known, the coexistence of micronutrient deficient and
      overweight/obese women can raise new and serious public health problems in the
      country. Second, the Egyptian food subsidy program, which lowers the relative
      prices of energy-dense, nutrient-poor food items, can be one of the major factors
      for the emergence of overweight/obese and micronutrient deficient mothers in the
      country. Changing the orientation of the food subsidy program may help to
      simultaneously address this double burden of mothers' malnutrition.

PMID- 17449339
TI  - Severe mutilating injuries to the hand: guidelines for organizing the chaos.
AB  - Major hand injuries have become a rarity in Western countries. The fact that
      there are well trained teams devoted to their management, should not obscure the
      fact that the first emergency surgeon has the major role of setting the
      foundations for a reconstruction. Understanding the goal to be sought: the
      'acceptable hand' (one with three fingers, with near normal length, near normal
      sensation and a functioning thumb), is hoped to be of great help in primary care.
      Preservation of vital structures such as joints, flexor tendons, and vessels, in
      the initial debridement, which will help to build this 'acceptable hand' are
      discussed. The general guidelines for management of finger amputation and soft
      tissue problems are also given.

PMID- 17449340
TI  - Rupture of PIP breast implants.

PMID- 17449341
TI  - Purse-string closure of scalp defects following tissue expansion: an effective
      aesthetic alternative.
AB  - Primary closure of scalp defects under tension can be complicated by scar
      widening and alopecia, and large defects usually require the use of local flaps,
      skin grafts or free flaps. Tissue expansion facilitates the use of local flaps to
      cover large defects, but multiple expanders and complex flaps with extensive
      incisions may cause significant scars and alopecia. We describe a purse-string
      closure of expanded scalp tissue following excision of a large congenital nevus
      sebaceous. This scalp reconstructive technique minimises iatrogenic scars and
      uses the predictable forces of scar contracture and skin re-draping to achieve a
      superior aesthetic result.

PMID- 17449342
TI  - Anatomical bases of the second toe composite dorsal flap for simultaneous skin
      defect coverage and tendinous reconstruction of the dorsal aspect of the fingers.
AB  - Coverage of the dorsal aspect of the fingers is difficult, especially when the
      soft tissue defect is large and involves extensor apparatus and joints. Tendinous
      and/or articular reconstruction is not usually performed simultaneously with
      cutaneous repair. The aims of this study were: (1) to accurately determine the
      precise position of the first common dorsal metatarsal artery (FDMA) on the
      dorsal aspect of the foot, and (2) to enumerate the anatomical structures which
      could be harvested 'en-bloc' in order to design composite flaps. The precise
      position of the FDMA was studied from 22 anatomical specimens after selective
      injection of the arterial network. Its cutaneous area measured 75 x 40 mm on
      average. The extensor apparatus of the second toe was supplied by the FDMA and
      its lateral branch to the second toe by 2.7 branches on average over a length of
      approximately 75 mm. The medial dorsal digital artery was generally the main
      source of blood supply to the proximal interphalangeal joint (PIP), capsule,
      ligaments, head of proximal phalanx and base of middle phalanx. It is then
      possible to design composite flaps including both skin and extensor apparatus,
      and total or partial PIP joint, if necessary, based on the FDMA and the medial
      dorsal digital artery, without prejudice to the second toe. The average length of
      the arterial pedicle (60 mm) makes its suture to the dorsal metacarpal artery,
      the dorsal carpal branch or the radial artery easy. The harvesting technique for
      such a flap is described for each anatomical type of FDMA; it has to be adapted
      to both the type and extent of the defect. Its use is in accordance with the
      modern classical principle of 'all in one stage with early mobilisation', thanks
      to adequate coverage whose blood supply does not depend on local vascularisation,
      and which brings its own physiological vascular supply.

PMID- 17449343
TI  - A novel dual inhibitor of calpains and lipid peroxidation (BN82270) rescues the
      cochlea from sound trauma.
AB  - Free radical and calcium buffering mechanisms are implicated in cochlear cell
      damage that has been induced by sound trauma. Thus in this study we evaluated the
      therapeutic effect of a novel dual inhibitor of calpains and of lipid
      peroxidation (BN 82270) on the permanent hearing and hair cell loss induced by
      sound trauma. Perfusion of BN 82270 into the scala tympani of the guinea pig
      cochlea prevented the formation of calpain-cleaved fodrin, translocation of
      cytochrome c, DNA fragmentation and hair cell degeneration caused by sound
      trauma. This was confirmed by functional tests in vivo, showing a clear dose
      dependent reduction of permanent hearing loss (ED50 = 4.07 microM) with almost
      complete protection at 100 microM. Furthermore, BN82270 still remained effective
      even when applied onto the round window membrane after sound trauma had occurred,
      within a therapeutic window of 24 h. This indicates that BN 82270 may be of
      potential therapeutic value in treating the cochlea after sound trauma.

PMID- 17449346
TI  - Hepatocellular carcinoma (HCC): an update.
AB  - In the absence of large randomized trials, the current treatment strategy for
      hepatocellular carcinoma (HCC) remains a matter of choice depending mostly on
      retrospective studies, experience of centers, and the technical therapeutic
      possibilities. In fact, treatment decisions must be based on HCC extension and
      liver function, which is dependent on underlying liver disease. Cirrhosis limits
      therapeutic choices, life expectancy, and tolerance to therapy. Surgical
      resection and/or local destruction are the most common curative treatments.
      Orthotopic liver transplantation is probably the best treatment for small HCC
      developed in cirrhosis because it treats tumor, cirrhosis, and preneoplastic
      lesions at the same time. However, this treatment method is feasible in fewer
      than 5% of cases. Adjuvant treatments include transarterial chemoembolization,
      chemotherapy, polyprenoic acid, interferon, adoptive immunotherapy, and intra
      arterial radioactive lipiodol. Results from trials warrant confirmation in larger
      randomized trials to show a clear survival benefit on recurrence rate, secondary
      prevention, and overall survival. Chemoembolization is the only palliative
      treatment that has been proven to be active, unlike systemic chemotherapy,
      immunotherapy, and hormone therapy, whose activity is largely questionable and
      must all be restricted to clinical trials. Possible future therapeutic strategies
      include epidermal growth factor receptor inhibitors, antivascular endothelial
      growth factor therapies, cyclin D inhibitors, and HMG-CoA reductase inhibitors.

PMID- 17449347
TI  - Molecular mechanisms in Barrett's metaplasia and its progression.
AB  - The dramatic increase in the incidence and poor overall survival rates of
      esophageal/gastroesophageal junction adenocarcinoma underscore the necessity to
      discover molecular markers that can be used for risk assessment, early diagnosis,
      and targeted therapeutic intervention. Barrett's esophagus (BE) is proposed to
      represent a precursor of esophageal/gastroesophageal junction adenocarcinoma. BE
      progression to invasive cancer is defined by a metaplasia-dysplasia-carcinoma
      progression characterized by an increasing accumulation of genetic changes
      associated with alterations in molecular gatekeepers of cell circuitries and
      tissue homeostasis. Using a combination of in situ tissue-based and high
      throughput analyses, we investigated alterations of cell-cycle regulators and
      inflammation-associated molecular effectors. Our data suggest a potential
      synergistic effect of these alterations for the BE progression to cancer, and
      underscore the potential use of these markers: (1) in molecular panels assessing
      cancer risk in BE patients; and (2) as potential therapeutic targets for
      chemopreventive interventions and to enhance response to anti-neoplastic
      therapies.

PMID- 17449348
TI  - Population genetic tools: application to cancer.
AB  - The availability of a reference human genome sequence, an increasingly dense
      catalog, knowledge of common genetic variation, and new developments in
      technology present an unprecedented opportunity to systematically explore the
      genetic basis of complex human diseases such as cancer. An understanding of the
      common mutations that can cause distinct human cancers will be critical for
      identifying new targets for drug discovery, patient stratification for clinical
      trials, and analysis of drug response data to delineate classes of patients that
      respond to therapy. The genome structure of cancer can be examined in several
      ways: (1) large-scale case-control or family studies can investigate germline
      mutations; and (2) state-of-the-art genomic technologies (eg, high-density
      oligonucleotide arrays and targeted re-sequencing), can identify somatic
      alterations. Combined, these approaches will lead to a better understanding of
      the cancer genome.

PMID- 17449349
TI  - Treatment of advanced pancreatic cancer.
AB  - Chemotherapy for the treatment of pancreatic carcinoma is clearly evolving.
      Recent studies have provided the first evidence in more than a decade that
      combining gemcitabine with another systemic agent can improve outcome over that
      achieved with standard gemcitabine monotherapy in patients with advanced disease.
      Particularly promising are the gemcitabine/capecitabine (Gem-Cap) combination,
      which showed a significant survival benefit over single-agent gemcitabine in a
      large phase III study; gemcitabine/oxaliplatin combinations, some of which use a
      modulated gemcitabine infusion schedule; and gemcitabine-based combinations with
      targeted therapies, based on a significant survival benefit achieved with
      gemcitabine plus the epidermal growth factor receptor inhibitor erlotinib in the
      phase III setting, as well as encouraging phase II results with cetuximab and
      bevacizumab. Further advances will probably be made with combinations of targeted
      therapies. Better understanding of the carcinogenesis of this very aggressive
      cancer is also needed.

PMID- 17449350
TI  - 3'-deoxy-3'-(18)F-fluorothymidine (FLT) positron emission tomography for early
      prediction of response to chemoradiotherapy--a clinical application model of
      esophageal cancer.
AB  - Early detection of response to neoadjuvant chemoradiation in esophageal cancer
      may allow individualization of treatment strategies and avoidance of unnecessary
      treatment. Although positron emission tomography (PET) with
      [(18)F]fluorodeoxyglucose (FDG) permits detection of changes in tumor
      proliferation before any change in tumor size is evident, FDG-PET may fail to
      distinguish between residual tumor and inflammation and between complete response
      and partial response with substantial residual tumor burden. PET with the
      nucleoside analogue 3'-deoxy-3'-(18)F-fluorothymidine (FLT) is more accurate than
      FDG-PET in visualizing early changes in tumor proliferation. In a recent study in
      experimental models of esophageal cancer, FLT-PET was more accurate than FDG-PET
      in detecting early changes in proliferation following docetaxel and radiation
      therapy in human SEG-1 cells and mouse SEG-1 xenografts, including having a much
      stronger correlation with histologic findings. Clinical studies are needed to
      determine if FLT-PET can distinguish among degrees of response to neoadjuvant
      chemoradiation in patients with esophageal cancer. The ability to visualize tumor
      cell proliferation may also contribute to the ability to improve precision
      delivery of radiation therapy.

PMID- 17449352
TI  - Developing strategies for liver metastases from colorectal cancer.
AB  - Five-year survival rates of patients with liver metastases from colorectal cancer
      range from 30% to 40% for those who undergo successful resection procedures, and
      is almost nil among those unable to have surgery. However, improved chemotherapy
      strategies for nonoperable patients (specifically, the use of neoadjuvant
      oxaliplatin- and irinotecan-based regimens) have increased response rates and
      tumor downstaging such that 15% to 30% of initially nonoperable patients are able
      to have secondary, or rescue, surgery. Preliminary data also indicate that new
      targeted therapies should further increase response rates and thus resection
      rates. Operative techniques such as portal vein embolization and two-stage
      procedures for patients with multiple or large tumors, as well as use of
      cryosurgery and radiofrequency ablation, are also contributing to more effective
      removal of liver metastases from colorectal cancer. This brief report describes
      data supporting the expanding application of hepatectomy for patients with
      colorectal liver metastases.

PMID- 17449351
TI  - Adjuvant therapy for stage II and III colorectal cancer.
AB  - Considerable progress has been made in improving disease-free survival in stage
      III colon cancer with the use of adjuvant chemotherapy. In recent years, it has
      been shown that infusional 5-fluorouracil regimens maintain the efficacy and
      reduce toxicity associated with bolus 5-fluorouracil, that improved tolerability
      can be achieved with use of the oral fluoropyrimidine capecitabine, and that
      improved efficacy can be achieved by combining 5-fluorouracil/leucovorin with
      other cytotoxic agents (eg, oxaliplatin and irinotecan). Studies are ongoing to
      identify optimal adjuvant regimens in stage II or III disease and to identify the
      potential benefits of adding bevacizumab or cetuximab to adjuvant therapy.

PMID- 17449368
TI  - [Medical English in medical school: the French experience].
AB  - OBJECTIVES: English classes were made compulsory in French medical schools by a
      1992 statute. The aim of this work is to describe current characteristics of this
      teaching program. METHODS: A questionnaire designed by experts in the teaching of
      medical English was sent to the 41 medical schools in metropolitan France. The
      questionnaire covered five different areas (the number of class hours, students,
      and teachers; evaluation and marking methods; curriculum content and pedagogical
      methods, student and teacher profiles, and the teaching of English to
      postgraduate students). RESULTS: Twenty-six questionnaires were returned and
      evaluated, and all reported teaching English. Duration of instruction averages
      88+/-30 hours. English is compulsory in 96% of responding school and is taught
      mainly during the second and third years. Medical English is taught most often
      (68%). Permanent or temporary instructors teach relatively small classes. In 52%
      of cases, a doctor participates in the class. In 36% of cases, advanced
      postgraduate classes are organized for doctors. CONCLUSION: The teaching of
      English is now widely accepted in French medical schools, and it is developing.
      Nevertheless, we can hope that it will benefit from a wider range of pedagogical
      tools, notably by combining the existing classroom methods with training periods
      in English-speaking countries.

PMID- 17449369
TI  - [Fibrous solitary tumor of the pleura].

PMID- 17449370
TI  - [La Presse Medicale credits your CME].

PMID- 17449371
TI  - [Pathophysiology of systemic lupus erythematosus].
AB  - Innate immunity is directly implicated in the pathophysiology of lupus through
      the dendritic cell system and the activation by immune complexes of some toll
      like receptors (TLR). Interferon-alpha plays a key role in the pathophysiology of
      lupus and represents a promising target for immune therapy. Dendritic cells are
      activated and able to capture large quantities of nuclear antigen-containing
      bodies to stimulate specific adaptive immune response.

PMID- 17449372
TI  - [Human pulmonary trichomonoses].
AB  - Colonization of human lungs by various Trichomonas species is a frequent
      occurrence, but is unknown to most physicians. At this site of infection, the
      parasite develops into an amoeboid form that renders it unrecognizable. For this
      reason it has been overlooked until recently. Morphological identification is not
      feasible under these conditions and molecular tools provide the only means of
      identification. The species involved are not restricted to Trichomonas tenax, a
      saprophyte of the mouth that is usually cited in the rare cases of
      pleuropulmonary trichomoniasis reported in the literature. The recent discovery
      of species previously unknown in humans raises further questions, including the
      zoonotic potential of these microorganisms and the existence of species of animal
      origin that have adapted to humans. Anaerobiosis in poorly ventilated alveolar
      lumen, rather than immunodepression, seems to be the factor that promotes
      proliferation of this parasite. The diagnosis of trichomoniasis and its treatment
      by specific drugs will make it possible to evaluate the pathogenicity of these
      parasites.

PMID- 17449373
TI  - [Vasculitis management: discovery of antineutrophil cytoplasmic antibodies
      (ANCA)].

PMID- 17449374
TI  - Hemodynamic studies on brain CT perfusion imaging with varied injection rates.
AB  - OBJECTIVE: This study aimed to determine a contrast medium injection rate that
      ensures both accuracy for data and safety for operation by comparing hemodynamic
      parameters of brain CT perfusion imaging with varied injection rates. METHODS:
      Twenty-four healthy volunteers were divided into three groups based on contrast
      medium injection rates (4.5, 6.0, and 7.5 ml/s). For all subjects, CT perfusion
      scanning was started at 4 s after antecubital venous bolus of contrast media
      injection. A perfusion-analyzing software package was used to produce a time
      density curve in the anterior cerebral artery and the superior sagittal sinus and
      calculate the regional cerebral blood flow (rCBF) in the gray matter and the
      white matter. The hemodynamic indices were compared among the three groups, and
      statistical analysis was carried out using the F test. RESULTS: The time for the
      arterial rise to reach the peak value for the 7.5-ml/s group was only 0.2 s ahead
      of the initiation time for the rise of the superior sagittal sinus. The
      differences of rCBF in the gray matter and the white matter among the three
      groups were statistically significant. rCBF in the gray matter and the white
      matter for the 7.5-ml/s group was 52.8 ml x min(-1) 100 g(-1) . (+/-3.1) and 21.9
      ml x min(-1) . 100 g(-1) (+/-2.4), respectively. CONCLUSIONS: The use of the 7.5
      ml/s injection rate can meet the prerequisite of the maximum slope model, and the
      resulting rCBF can be very close to that measured by positron emission
      tomography. Therefore, 7.5 ml/s was an ideal contrast medium injection rate.

PMID- 17449375
TI  - Value of MRI in the surgical planning of invasive lobular breast carcinoma: a
      prospective and a retrospective study of 57 cases: comparison with physical
      examination, conventional imaging, and histology.
AB  - PURPOSE: The objective of this study was to determine the value of magnetic
      resonance imaging (MRI) for the surgical planning of invasive lobular carcinoma
      (ILC)-a diagnostic challenge for radiologists. MATERIALS AND METHODS: Fifty-seven
      patients with histologically proven ILC were studied between 1998 and 2006. All
      patients underwent physical examination, mammography, ultrasound, and MRI. All
      anomalies detected were graded using the Breast Imaging Reporting and Data System
      (BI-RADS) classification, and careful research was made for the presence of
      multifocal/multicentric disease. RESULTS: On MRI, 72% of images were visualized
      as masses and 18% corresponded to non-mass-like enhancements. The size
      correlations, compared with histological findings, were .88 (MRI; P<.001), .57
      (ultrasound), .53 (physical examination), and .40 (mammography). The kappa
      correlations for multifocality were .87 (MRI), .22 (ultrasound), and .22
      (mammography). MRI had a sensitivity of 100% and a specificity of 87%. Forty-nine
      percent of therapeutic strategy cases were modified. CONCLUSION: MRI is
      unquestionably valuable for the management of ILC. It provides the most accurate
      estimate of tumor size and is highly sensitive for multifocal disease. Its main
      drawback is its lack of specificity, which requires preoperative histological
      verification. MRI often justifies the modification of the initial therapeutic
      strategy, generally ruling out conservative procedures.

PMID- 17449376
TI  - Delayed femoral pseudoaneurysm formation after percutaneous coronary
      intervention.
AB  - Five femoral pseudoaneurysms were treated among 573 patients who underwent
      percutaneous coronary interventions. Four of the five patients suffered from
      diabetes mellitus and four patients needed regular hemodialysis due to chronic
      renal failure. One patient's course was complicated by infection. One patient was
      healed by compression therapy and four patients were treated successfully by
      surgery, which included an extraanatomic bypass and a thromboendoarterectomy.
      Diabetes and regular hemodialysis are major risks for the formation of femoral
      pseudoaneurysm after catheter intervention at present.

PMID- 17449377
TI  - Peripheral lung cancer: relationship between multi-slice spiral CT perfusion
      imaging and tumor angiogenesis and cyclin D1 expression.
AB  - The aim of this study was to investigate the relationship between 16-slice spiral
      CT perfusion imaging and tumor angiogenesis and cyclin D1 expression in patients
      with peripheral lung cancer. Fifty-eight patients with peripheral lung cancer
      underwent 16-slice spiral CT perfusion imaging. The CT perfusion imaging was
      analyzed for time density curve (TDC), perfusion parametric maps, and the
      respective perfusion parameters. Correlation between the respective perfusion
      parameters and immunohistochemical findings of microvessel density measurement
      and cyclin D1 expression was evaluated.

PMID- 17449378
TI  - Reduced computed tomography radiation dose in HIV-related pneumonia: effect on
      diagnostic image quality.
AB  - PURPOSE: The objective of this study was to compare the diagnostic quality of low
      dose computed tomography (CT) with that of standard-dose chest CT in the
      diagnosis of infectious lung diseases. MATERIALS AND METHODS: Thirty chest CT
      scans [high-resolution computed tomography (HRCT), 15; spiral CT, 15] were
      performed in HIV-positive patients with an infectious lung disease. Two
      additional slices were obtained at two lower exposures (HRCT, 120 kV/70 mAs and
      120 kV/50 mAs; spiral CT, 100 kV/56 mAs and 100 kV/40 mAs) after chest routine
      CT. Observers compared the quality of the images obtained at different parameters
      and image noise. Objective evaluation of image noise was also made. RESULTS:
      Diagnostic image quality was excellent in 93% of the low-dose HRCT scans and in
      86% of the low-dose spiral CT scans, rates that are always acceptable in any
      case. Significant differences were found in noise levels between the low-dose and
      reference scans; however, artifacts did not compromise detection of
      abnormalities. In HRCT, a mean reduction of 77% from the standard technique to
      the low-dose scan is possible in total and in lung effective doses. In spiral CT,
      this reduction is lower at 71%. These values can reach a further reduction with
      ultra-low-dose imaging (84% in HRCT and 80% in spiral CT). CONCLUSIONS: Chest CT
      image quality appears to be adequate to evaluate pulmonary infectious diseases,
      even with an effective reduction in radiation dose. Standard-dose CT with a
      higher patient effective dose may be appropriate for selected cases.

PMID- 17449379
TI  - Diagnostic value of CTE in patients with Crohn's disease.
AB  - OBJECTIVE: The goal of our study was to compare the accuracy of computed
      tomography enteroclysis (CTE) to that of biopsy in detecting bowel wall
      alterations of the terminal ileum in Crohn's disease (CD). SUBJECTS AND METHODS:
      A total of 43 patients with either diagnosed or suspected CD (16 females, 28
      males) underwent CTE and ileoscopy. Ileoscopy diagnosed 35 patients with CD of
      the ileum, while 8 patients served as the control group. RESULTS: Computed
      tomography enteroclysis detected CD in 31 patients (88%) and in none of the
      control group. According to the criteria used for evaluation of small bowel loop
      distension, 31 cases were (72%) with optimal distension, nine cases (%21) with
      good distension, and three cases (7%) with poor distension. Computed tomography
      enteroclysis showed that mean ileal wall thickness in patients with CD was 6.8 mm
      (range, 9.5-4.1 mm) and 1.79 mm in patients in the control group (range, 2.20
      1.38 mm). Mean postcontrast wall density in patients with CD was 81.9 HU (range,
      111.6-52.2 HU) and 41.1 HU (range, 49.8-22.4 HU) in the control group. Mean
      postcontrast wall density in 17 patients with active CD was 97 HU (range, 67-123
      HU) and 62 HU (range, 46-87 HU) in 18 CD patients in remission. We calculated
      that the overall sensitivity and specificity of CTE in detecting the severity of
      CD were 89% and 100%, respectively. Positive predictive value was 100%; negative
      predictive value was 89%. CONCLUSION: Our results indicate that CTE can reveal CD
      involvement of small bowel accurately and allow assessment of the degree of
      disease activity.

PMID- 17449380
TI  - Shift in imaging modalities of gastrointestinal tract through 25 years and its
      impact on patient ionizing radiation doses.
AB  - We wanted to explore the shift in modalities when diagnosing the gastrointestinal
      tract through the last three decades and see how this has influenced on the
      radiation doses given to this patient population. Activity reports from a central
      hospital in the years of 1979-2003 have been reviewed. The x-ray based modalities
      have decreased, while there has been a marked increase in colonoscopies,
      gastroscopies, ultrasound, and magnetic resonance cholangiopancreatography. This
      has caused a reduction in collective effective radiation dose of 54%.

PMID- 17449381
TI  - Anterior transverse ligament of the knee: MR imaging and anatomic study using
      clinical and cadaveric material with emphasis on its contribution to meniscal
      tears.
AB  - PURPOSE: To study the anatomy of the anterior transverse ligament of the knee
      (TL) and to correlate its presence with the occurrence of meniscal tears.
      PATIENTS: MR imaging studies of the knee performed over a 1-year period in 49
      patients were reviewed by two readers in consensus for the presence and
      morphology of the TL. Ten cadaveric specimens underwent MR imaging and sectioning
      for anatomic and histological study. RESULTS AND CONCLUSION: The TL is a frequent
      anatomical structure that usually connects the leading edge of the core of the
      anterior horn of the MM, to the external portion of the anterior horn of the LM,
      and in many instances with the ligamentum muscosum. There is an association
      between the presence of a TL attachment and the presence of tears in the MM.

PMID- 17449382
TI  - Diffuse cranial nerve and cauda equina lesions associated with breast cancer.
AB  - We report on the case of a patient with breast cancer with diffuse cranial nerve
      and cauda equina lesions. Magnetic resonance imaging of the patient's brain and
      spinal cord showed diffuse abnormal enhancement and slight enlargement of the
      cranial nerves and cauda equina. Although the results of subsequent testing for
      two antineural antibodies were negative, paraneoplastic sensorimotor neuropathy
      associated with breast cancer was considered to be the most likely clinical
      diagnosis.

PMID- 17449383
TI  - Nasoalveolar cyst: imaging findings in three cases.
AB  - The authors describe the computed tomography (CT) and magnetic resonance (MR)
      imaging findings of three cases of nasoalveolar cysts. Few previous reports have
      presented the CT and MR imaging findings of nasoalveolar cysts in detail,
      although a considerable number of reports have described these cysts. In the
      cases described, CT and MR images showed various densities and signal intensities
      due to different viscosities of intracystic fluid, and adjacent bony erosion of
      the anterior maxillary buccal cortex was seen in all cases.

PMID- 17449385
TI  - Magnetic resonance imaging of gluteal intramuscular myxoma.
AB  - Gluteal intramuscular myxomas with MR images have not been reported before. A 45
      year-old man presented with a palpable mass in his right buttock for several
      months. Magnetic resonance imaging showed an intramuscular cystic lesion with
      homogeneous signal intensity at the right gluteus muscle, and the mass had thin
      peripheral enhancement after gadolinium administration. The patient was treated
      by marginal excision of the tumor. Histologic diagnosis was compatible with
      intramuscular myxoma.

PMID- 17449384
TI  - Use of multidetector CT angiography and 3D postprocessing in a case of pulmonary
      sequestration.
AB  - Pulmonary sequestration is a pulmonary malformation in which a portion of
      nonfunctioning bronchopulmonary tissue is separated from the rest of the lung
      parenchyma. We report the case of a 48-year-old woman with history of chronic
      pneumonia, studied with computed tomography and in whom we obtained three
      dimensional evaluation of the pathological structures.

PMID- 17449386
TI  - The impact of the journal and its impact on the journal.

PMID- 17449387
TI  - A true story of "organ-based medicine", or when did we stop thinking?

PMID- 17449388
TI  - Role of tumor markers in patients with solid cancers: A critical review.
AB  - The measurement of tumor markers is currently one of the most rapidly growing
      areas in laboratory medicine. Lack of sensitivity and specificity preclude the
      use of most existing markers for the early detection of malignancy. For patients
      with diagnosed malignancy, however, markers are potentially useful in determining
      prognosis, predicting therapeutic response, maintaining surveillance following
      curative surgery and monitoring therapy in advanced disease. Clinically useful
      markers include CEA in the surveillance of patients with diagnosed colorectal
      cancer, AFP and HCG in the management of patients with non-seminomatous germ cell
      tumors, HCG in the management of patients with trophoblastic disease, CA 125 for
      monitoring therapy in patients with ovarian cancer, estrogen receptors for
      predicting response to hormone therapy in breast cancer and HER-2 for the
      identification of women with breast cancer likely to respond to trastuzumab
      (Herceptin). Although widely used, the impact of PSA screening in reducing
      mortality from prostate cancer remains to be shown.

PMID- 17449389
TI  - Dengue fever in travellers: A challenge for European physicians.
AB  - Dengue fever (DF) is one of the world's emerging infectious diseases. The steady
      increase in European tourists, as well as soldiers serving on peacekeeping
      duties, in endemic areas, coupled with the present resurgence of dengue, raises
      the risk of exposure for a large number of European travellers. Significant
      numbers of travellers have, in fact, developed DF. There is a risk of dengue
      haemorrhagic fever (DHF) in travellers who revisit the same place, and they have
      the potential not only to acquire, but also to spread, the dengue viral
      infection. Of concern is the potential for a dengue outbreak in a previously
      dengue-free country through imported cases. Another major concern is the
      potential area of dengue transmission, due to spread of its vectors through
      sizeable parts of southern Europe. In addition to the risk of haemorrhagic fever
      in returning tourists, the introduction of DF by returning travellers, whether
      they have symptoms or are unaffected by signs and symptoms of the disease, poses
      a threat to health systems in Europe.

PMID- 17449390
TI  - Circulating vascular endothelial growth factor is unaffected by acute
      hyperglycemia and hyperinsulinemia in type 1 diabetes mellitus.
AB  - BACKGROUND: Circulating levels of vascular endothelial growth factor (VEGF) may
      predict microvascular complications in type 1 diabetes mellitus and are elevated
      when metabolic control is poor. We tested whether serum VEGF is influenced by
      prevailing glucose and insulin levels. METHODS: In 15 type 1 diabetic patients,
      serum VEGF, plasma von Willebrand factor antigen (vWF-Ag), and serum soluble
      intercellular adhesion molecule-1 (s-ICAM) levels were measured after 210 min of
      hyperglycemia (blood glucose target 12.0 mmol/l) and hyperinsulinemia (insulin
      infused at 120 mU/kg/h), alone and in combination. These were then compared with
      the levels obtained at the end of a 210-min normoglycemic (blood glucose target
      5.0 mmol/l) standard insulin clamp (insulin infused at 30 mU/kg/h). RESULTS: VEGF
      (p>0.60) as well as vWF-AG (p>0.80) and s-ICAM (p>0.20) remained unchanged at the
      end of the three intervention periods. CONCLUSION: These findings suggest that no
      special precautions, in terms of concurrent measurement of glucose or timing of
      insulin administration, are necessary when interpreting circulating VEGF in this
      patient category.

PMID- 17449391
TI  - Eosinophilia: A study of 100 hospitalized patients.
AB  - BACKGROUND: Eosinophilia accompanies a large number of diseases and conditions,
      but information is lacking about the clinical characteristics of patients who are
      hospitalized due to this abnormality. Our aim was to determine the clinical
      profile and most informative diagnostic tests in patients hospitalized in a
      tertiary hospital because of hypereosinophilia. METHODS: A retrospective review
      was done of the medical records of all patients hospitalized in a large urban
      medical center due to hypereosinophilia. All relevant clinical, laboratory, and
      imaging data were analyzed. RESULTS: A total of 100 patients were included in the
      study (58 males and 42 females, mean age 55.2+/-29 years). The blood eosinophil
      blood count was 4107+/-7254/mul (mean+/-SD) and this usually persisted for a few
      months. The cause of the eosinophilia was asthma or other atopic disease in 13%
      of the cases, allergic drug reaction in 6%, eosinophilic pneumonia in 10%,
      neoplastic diseases in 10%, idiopathic hypereosinophilic syndrome in 8%, Churg
      Strauss Syndrome in 4%, infections in 10%, allergic fungal disease in 2%, and
      skin diseases in 3%; the cause remained unknown in 34% of cases. CONCLUSION:
      Guidelines are suggested for the investigation of patients with eosinophilia,
      including the level of the eosinophilia associated with specific diseases and the
      most informative diagnostic tests.

PMID- 17449392
TI  - Oral anticoagulation in atrial fibrillation: A pan-European patient survey.
AB  - BACKGROUND: Anticoagulation with vitamin K antagonists (VKAs) provides effective
      stroke prophylaxis in patients with atrial fibrillation (AF). Optimisation of
      such therapy requires frequent monitoring, dose adjustments and stringent
      lifestyle restrictions. We conducted a large multinational survey in patients
      with chronic AF to gain insights into their perceptions and understanding of VKA
      use. METHODS: Eligible patients were adults with AF who had been prescribed VKAs
      for at least 1 year. A total of 711 patient interviews were conducted in seven
      European countries during June and July 2004. RESULTS: The majority of patients
      (58% male; mean age 68 years) claimed to understand their treatment programme;
      despite this, only 7% knew that VKA use is aimed at preventing strokes and 24%
      stated that they would have liked more information. Patients attended an average
      of 14 monitoring sessions in the previous year; however, 21% missed appointments,
      especially younger patients (<65 years). The International Normalized Ratio (INR)
      was within the target range in most or all of the last five to ten visits in 64%
      of patients; nonetheless, 38% were not aware that an INR outside the target range
      is associated with health risks. On average, patients required dose adjustments
      every four sessions. VKA treatment impacted 67% of patients in terms of diet,
      socialising, career and independence, especially younger patients (74%).
      CONCLUSIONS: Monitoring, dose adjustments and lifestyle restrictions to optimise
      the intensity of anticoagulation with VKAs are problematic for patients with AF,
      and their knowledge of the consequences of such therapy is often poor.

PMID- 17449393
TI  - Characteristics of low-risk patients hospitalized with community-acquired
      pneumonia.
AB  - BACKGROUND: Despite the wide distribution of different severity scoring systems
      for community-acquired pneumonia (CAP) patients, low-risk patients are frequently
      hospitalized, contrary to current recommendations. The aim of our study was to
      determine the rate, clinical characteristics, and outcome of low-risk patients
      with CAP admitted to our institution. METHODS: During an 18-month period, we
      prospectively screened all patients admitted to the Division of Internal Medicine
      with a presumptive diagnosis of CAP. Pneumonia Outcome Research Team (PORT) score
      and pneumonia severity index (PSI) were calculated for all patients during the
      first 24 h. RESULTS: A total of 591 patients had a diagnosis of CAP. Some 196
      patients (33.1%) were low-risk (PSI class I, II), 98 (16.6%) intermediate (PSI
      III), and 297 (50.3%) high-risk patients (PSI IV, V). Patients in low-risk
      classes were younger (45.5+/-15.8 vs. 65.0+/-12.5 and 74.9+/-11.8 years,
      respectively, p<0.001) and had fewer background diseases. They had shorter
      hospitalizations than intermediate- and high-risk groups (4.4+/-3.2, 5.3+/-3.4,
      and 6.8+/-6.4 days, respectively, p<0.001). There was a significant difference in
      30-day mortality between the different risk groups: 0% in the low-risk, 2.0% in
      the intermediate-risk, and 9.4% in the high-risk group (p<0.001). CONCLUSION: The
      considerable proportion of low-risk patients hospitalized due to CAP was found to
      be comparable to the stable 30% rate reported in the literature. We conclude that
      physicians tend to opt for a wide safety range when considering a CAP patient
      hospitalization, rather than make a decision based only on severity score
      calculation.

PMID- 17449394
TI  - NT-pro-BNP is associated with long-term outcome in a heterogeneous sample of
      cardiac inpatients.
AB  - BACKGROUND: B-type natriuretic peptides (NP) are excellent predictors of
      mortality in selected patients with heart failure and coronary heart disease. Up
      to now, the association of NPs with cardiovascular outcome has not been evaluated
      in multi-morbid populations with a broad spectrum of cardiovascular disease.
      METHODS: NT-pro-BNP was measured at discharge in 615 inpatients from a cardiology
      department of a university hospital. The association of discharge NT-pro-BNP with
      long-term outcome was examined during a median follow-up time of 1130 days.
      RESULTS: NT-pro-BNP was significantly elevated in patients who died, developed
      ischemic stroke, or were hospitalized due to acute heart failure, but not in
      patients who developed myocardial infarction or underwent coronary angioplasty
      compared to patients without any endpoint. Patients with supramedian NT-pro-BNP
      values (>339 pg/ml) had significantly worse outcomes with respect to the combined
      endpoint (CE) of death, heart failure hospitalization, and stroke than patients
      with inframedian NT-pro-BNP values. After adjusting for age, gender, renal
      function, NYHA class, presence of diabetes, coronary 3-vessel disease, systolic
      and valvular dysfunction, NT-pro-BNP was a significant predictor of the CE. The
      AUC for NT-pro-BNP to predict the CE was 0.79 in the total population, 0.81 in
      patients with coronary heart disease or acute heart failure, and 0.74 in patients
      with other diagnoses. A NT-pro-BNP cut-off value of 240 pg/ml revealed a negative
      predictive value of more than 93% in all three groups. CONCLUSION: In a
      heterogeneous population of hospitalized cardiac patients, NT-pro-BNP measured at
      discharge predicts a poor cardiovascular outcome, independently of the
      cardiologic diagnosis and traditional risk factors.

PMID- 17449395
TI  - Plasma arginine vasopressin and atrial natriuretic peptide concentration in
      patients with hyponatremia at diagnosis and following treatment.
AB  - BACKGROUND: Much evidence for arginine vasopressin (AVP) and atrial natriuretic
      peptide (ANP) in the pathogenesis of hyponatremia in humans is based on single
      measurements. To study the roles of AVP and ANP in the pathogenesis and recovery
      of hyponatremia, sequential measurements of ANP and AVP were taken during
      treatment in a group of hyponatremic patients with different etiologies. METHODS:
      Consecutive adult patients with hyponatremia (serum Na <130 mmol/l) and healthy
      controls were studied. Volume status was determined by clinical and laboratory
      criteria. Plasma AVP and ANP, fractional sodium excretion, and urine osmolality
      were determined daily until serum Na was above 135 mmol/l or for at most 7 days.
      RESULTS: A total of 16 controls and 40 hyponatremic patients (12 normovolemic, 9
      hypervolemic, and 19 hypovolemic) were studied. Patients' plasma AVP on the first
      day [1.0 (0.3-2.3) ng/l] and on the last day [1.1 (0.3-2.5) ng/l] of the study
      did not differ from that of controls [0.7 (0.5-1.0) ng/l]. Serum sodium
      concentration increased significantly in patients between the first and the last
      day. Patients had significantly lower ANP concentrations, both on the first day
      [25 (15-46) ng/l] and on the last day [29 (17-46) ng/l], than controls [41 (28
      51) ng/l]. Plasma AVP was elevated relative to serum osmolality on the first day
      and to a lesser extent on the last day of the study. CONCLUSIONS: AVP is
      inappropriately high in a majority of hyponatremic patients. Plasma AVP and ANP
      concentrations do not change during treatment in hyponatremic patients despite a
      significant increase in serum osmolality. A low ANP concentration in clinically
      normovolemic and hypovolemic patients indicates volume depletion, which may lead
      to baroreceptor-stimulated AVP secretion.

PMID- 17449396
TI  - CPAP titration: Different methods for similar clinical results.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) is the main treatment for
      obstructive sleep apnea-hypopnea syndrome (OSAHS). Polysomnography (PSG) is the
      gold standard for CPAP titration. However, alternative methods have been sought
      to titrate CPAP at less expense in terms of time and resources. The aim of this
      study was to analyze CPAP success in controlling OSAHS symptoms and adverse
      effects by two titration methods. METHODS: This was a retrospective,
      observational cohort study in which 200 CPAP-naive patients who had been referred
      to our sleep laboratory and diagnosed with OSAHS were evaluated on two
      consecutive visits. During the first visit, an initial CPAP pressure was
      established either by split-night PSG or by using a mathematical formula. On the
      second visit, 1 month later, symptom persistence and adverse effects of CPAP
      treatment were assessed. RESULTS: Patients included were 157 males (78.5%) and 43
      females (21.5%) aged 56+/-10 years. 87 patients (43.5%) were titrated by PSG and
      113 (56.5%) using the formula. At the second visit, symptoms had improved
      significantly for both groups with no significant differences in the presence of
      adverse effects. The initial pressure had to be readjusted in five patients.
      CONCLUSIONS: This study suggests that formula titration can control symptoms as
      effectively as split-night titration. A prompt evaluation of the patient is
      advisable in order to ensure compliance with treatment and to correct possible
      adverse effects.

PMID- 17449397
TI  - Visceral leishmaniasis diagnosed in a patient with MALT lymphoma.
AB  - We report a case of visceral leishmaniasis in a 66-year-old female with a history
      of MALT lymphoma in the gastrointestinal tract. The patient presented with major
      hemorrhage per rectum and perforation of the small intestine. Due to unexplained
      decreasing platelets, lymphoma bone marrow involvement was suspected and bone
      marrow examination was performed. Surprisingly, Leishman-Donovan bodies were
      detected. The low platelet count, caused by the combination of MALT lymphoma and
      visceral leishmaniasis, appears to have aggravated the symptoms of the intestinal
      lymphoma. Leishmaniasis should be suspected even among asymptomatic patients with
      immune compromising illnesses and a travel history to areas where leishmaniasis
      is endemic.

PMID- 17449398
TI  - Acute vasculitis as a first manifestation of hairy cell leukemia.
AB  - Hairy cell leukemia (HCL) is a lymphoproliferative malignancy characterized by
      bone marrow, spleen, liver, and occasionally lymph node infiltration with hairy
      cells, usually accompanied by splenomegaly and pancytopenia. We report an unusual
      case of HCL in a 53-year-old woman with leukopenia and sudden onset of fever of
      unknown origin, arthritis, and generalized maculopapular exanthem. Skin biopsy
      revealed perivascular and/or vessel wall lymphocytic infiltration in the dermis.
      On the basis of bone marrow biopsy and flow cytometry, the diagnosis of HCL was
      established. A detailed, retrospective re-evaluation of the skin biopsy helped to
      identify hairy cells among the cells of the perivascular infiltrations. Small
      vessel vasculitis, as an atypical presentation, was found to predate a diagnosis
      of HCL. Recognition that vasculitis can reflect or antedate lymphoid malignancy
      may permit early diagnosis and aggressive treatment. A rapid response was
      obtained with a single course of cladribine.

PMID- 17449399
TI  - Hepatosplenic gammadelta T-cell lymphoma: A case report.
AB  - A 53-year-old man complained of weight loss, night sweats, and splenomegaly. The
      patient was diagnosed with stage IV hepatosplenic gammadelta T-cell non-Hodgkin's
      lymphoma, a highly aggressive and rare form of peripheral T-cell lymphoma. After
      completing CHOP chemotherapy, the patient relapsed. He did not respond to
      subsequent alemtuzumab therapy.

PMID- 17449400
TI  - Fasciitis-panniculitis syndrome simulating deep venous thrombosis.
AB  - Fasciitis-panniculitis syndrome (FPS) is a condition characterized by
      inflammation of the subcutaneous cellular tissue, the aponeurosis and,
      eventually, the muscles. A 49-year-old female who was previously diagnosed as
      having retroperitoneal fibrosis presented recurrent episodes of intermittent
      inflammation of her limbs that simulated deep venous thrombosis (DVT). Biopsy
      revealed panniculitis with involvement of the fascia, characterizing FPS.
      Clinical improvement was achieved after corticosteroid therapy. Prompt
      recognition of FPS is important in order to avoid inadequate therapeutic measures
      since FPS can clinically simulate infectious or vascular diseases.

PMID- 17449401
TI  - Isolated hypoaldosteronism: An overlooked cause of hyponatraemia.
AB  - We report three patients with hyponatraemia due to isolated hypoaldosteronism.
      Addison's disease was ruled out in each of these patients by a normal short
      synacthen test. Two patients had severe hyponatraemia and fluid restriction
      helped improve the sodium level only marginally. One was treated with
      demeclocycline, which did not prove to be effective. Subsequently, all three
      patients were found to have aldosterone deficiency and treatment with
      fludrocortisone caused their sodium levels to return to normal.

PMID- 17449402
TI  - Bilateral adrenal enlargement with an unexpected diagnosis.
AB  - A 78-year-old man, previously treated for prostate and colorectal cancer, was
      admitted to the hospital because of persistent fever. He was found to have
      bilateral large adrenal masses and adrenal insufficiency. Primary large B-cell
      lymphoma was proven by aspiration biopsy of the left adrenal gland. On
      presentation, no evidence of lymphoma outside the adrenal glands was found. The
      patient died before treatment could be initiated. The autopsy report is discussed
      briefly. Primary adrenal lymphoma is a rare entity and should be considered in a
      patient with bilateral adrenal masses without nodular involvement.

PMID- 17449403
TI  - Gastric pneumatosis following polychemotherapy.
AB  - Lung cancer is the most frequent cause of cancer deaths in the western world
      today. In our case, we present the history of a 62-year-old man with the
      diagnosis of the uncommon complication of an acute gastric pneumatosis following
      his palliative chemotherapy. This rare condition was first described more than
      100 years ago and has since been described in several distinctive clinical
      settings. To our knowledge, we present the first case of chemotherapy-related
      pneumatosis exclusively limited to the stomach wall but involving the portal
      veins and the spleen.

PMID- 17449404
TI  - A case of thyroid hormone resistance: Prospective follow-up during pregnancy and
      obstetric outcome.
AB  - We describe the case of a patient with resistance to thyroid hormone (R243W
      substitution) and her obstetric outcome. The patient gave birth to a healthy
      girl, unaffected by the R243W mutation. Two years later, following an uneventful
      pregnancy, a baby boy was born at term; he presented the same thyroid hormone
      receptor mutation as his mother. Follow-up of gestational thyroid hormone levels
      is reported during both pregnancies and related to obstetric outcome.

PMID- 17449405
TI  - Chronic inflammatory demyelinating polyneuropathy in an HCV-related cirrhotic
      patient with acute hepatitis B superinfection.

PMID- 17449406
TI  - Pseudohyperkalemia in a patient with rapidly progressive glomerulonephritis.

PMID- 17449407
TI  - Buerger's disease: Spinal cord stimulation may represent a useful tool for
      delaying amputation in young patients.

PMID- 17449408
TI  - Acute hemolytic anemia following infectious mononucleosis.

PMID- 17449409
TI  - Eleven years on: a clinical update of key areas of the 1996 lung allograft
      rejection working formulation.

PMID- 17449410
TI  - Potential refinements of the International Society for Heart and Lung
      Transplantation primary graft dysfunction grading system.
AB  - Primary graft dysfunction (PGD) is responsible for significant morbidity and
      mortality after lung transplantation and The International Society for Heart and
      Lung Transplantation (ISHLT) Working Group on PGD has recently reported
      standardized consensus criteria, based on the recipient arterial blood-gas
      analysis and chest X-ray findings, to define PGD and determine its severity
      (grade range, 0-3). The grading system has been shown to predict post-transplant
      outcomes; however, further evaluation and refinement of the validity of the
      grading system is an important next step to enhance its utility. In this review,
      we describe advantage and disadvantages of the current PGD grading system based
      on series of analyses we have conducted and possible options for its potential
      refinement. The suggested revisions are (1) additional assessment time points at
      6 and 12 hours should be included, (2) only bilateral infiltrates on chest X-ray
      (not unilateral infiltrates) should be considered as an infiltrate in bilateral
      lung transplants, (3) information from the chest X-ray is useful within 6 hours
      of final lung reperfusion (T0) but is not necessary to classify grade 3 at 12 to
      72 hours, (4) apply PGD grade to single and bilateral lung transplant separately,
      (5) all extubated patients should be considered as grade 0 to 1, (6) note if PGD
      grade is being defined by specific inclusion and exclusion criteria, including
      extubation, with clear chest X-ray, on nitric oxide or extracorporeal membrane
      oxygenation. Although, further evaluations of the PGD definition and grading
      system are needed, the suggested refinements in this review may further enhance
      the reliability and validity of the PGD grading system as an important new lung
      transplant study instrument.

PMID- 17449411
TI  - Management of pulmonary arterial hypertension with a focus on combination
      therapies.
AB  - Pulmonary arterial hypertension (PAH) is a rare but frequently fatal condition
      marked by vasoconstriction and vascular remodeling within small pulmonary
      arteries. The pathobiology of PAH involves imbalances in a multitude of
      endogenous mediators, which promote aberrant cellular growth, vasoconstriction
      and hemostasis within the pulmonary vascular tree. The mechanisms promoting these
      pathologic effects are complex. This complexity is highlighted by the many
      overlapping secondary messenger systems through which these mediators work. In
      light of this natural redundancy, it is not surprising that many of the drugs
      used to treat PAH, which have shown short-term efficacy, fall "short of the mark"
      in reversing or halting the progression of this disease in the long run. This
      very redundancy in pathways makes the case for the use of combination of drugs
      with differing mechanisms of action to treat PAH. Similar to what is now accepted
      as the standard of care for the treatment of cancer and left ventricular
      dysfunction, combination therapy has the greatest promise for inducing the most
      complete vascular remodeling of the pulmonary vasculature by "shutting down" as
      many of these pathologic pathways as possible. Combination therapies involving
      existing therapies or new agents with improved pharmacokinetic and/or
      pharmacodynamic properties represent an emerging clinical paradigm for patients
      with sub-optimally managed disease. As emerging data in this field of therapy
      comes to fruition, further reductions in the morbidity and mortality associated
      with PAH will manifest. The goal of this report is to review the philosophy of
      combination therapy and present the available data in this area of study.

PMID- 17449412
TI  - Sudden death prior to pediatric heart transplantation: would implantable
      defibrillators improve outcome?
AB  - OBJECTIVES: The goal of this study is to determine the incidence of sudden
      cardiac death in children with cardiomyopathy prior to pediatric heart
      transplantation. BACKGROUND: Recent primary prevention trials of implantable
      cardiac defibrillator (ICD) therapy in adults with ischemic and non-ischemic
      cardiomyopathy have shown a survival benefit. The incidence of sudden death, and
      thus the likelihood of improved survival with ICD therapy, in children with
      cardiomyopathy is currently unknown. METHODS: The Pediatric Heart Transplant
      Study (PHTS) database was retrospectively queried for patients < or =18 years of
      age who died from any cause after listing for but prior to heart transplantation.
      Patients having arrhythmic or sudden death were included for study. Clinical and
      demographic variables were examined to identify higher-risk sub-groups. RESULTS:
      Of the 2,392 patients in the PHTS database, 420 (17.6%) died prior to heart
      transplantation. Only 32 deaths (1.3% of total listed, 7.6% of total deaths) were
      sudden or arrhythmic in nature. Patients with ischemic cardiomyopathy had an
      increased risk of sudden death (relative risk = 6.92). Presence of congenital
      heart disease and United Network for Organ Sharing (UNOS) status at listing were
      not associated with an increased risk of sudden death. CONCLUSIONS: The overall
      incidence of sudden death in children awaiting heart transplantation is low;
      therefore, uniform implantation of ICDs for the primary prevention of sudden
      death is unlikely to improve survival in this population. Children with ischemic
      cardiomyopathy appear to have a higher risk of sudden death and may benefit from
      ICD therapy.

PMID- 17449413
TI  - Home inotropic therapy in children.
AB  - BACKGROUND: Inotropic therapy is a well-established practice for children with
      advanced congestive heart failure (CHF). Traditionally, children have been
      maintained on inotropic therapy in the hospital under close, monitored
      supervision. Changes to UNOS listing criteria now allow patients awaiting heart
      transplantation to be discharged to home yet maintain 1B status. In adults, home
      inotropic therapy has been shown to be a safe and cost-effective bridge to
      transplantation. To date, there are limited data on the use of home inotropic
      therapy in children. METHODS: We reviewed the safety and efficacy of continuous
      ambulatory home inotropic therapy in children. Data were obtained from a single
      institution from January 2000 to January 2007. RESULTS: There were 14 pediatric
      patients with end-stage CHF, who received home intravenous inotropic therapy. The
      indications for home inotropic therapy included palliative care (n = 8) and
      awaiting heart transplantation (n = 6). Patients ranged in age from 6 to 18 years
      (median 14.5 years). The majority of subjects (n = 11) received milrinone at a
      dose of 0.5 to 1.0 mug/kg/min, 2 received dobutamine at 5 mug/kg/min, and 1
      received both agents. Duration of therapy ranged from 14 to 476 days (median 68
      days). There were 26 hospital re-admissions and 4 suspected catheter infections.
      No unexpected deaths or pump failures occurred. CONCLUSIONS: Based on this
      initial review, continuous home inotropic therapy in children with CHF is safe
      with few complications. Home inotropic therapy may result in substantial cost
      savings and improve family dynamics by avoiding prolonged hospitalization.

PMID- 17449414
TI  - Pre-transplant risk factors for chronic renal dysfunction after pediatric heart
      transplantation: a 10-year national cohort study.
AB  - BACKGROUND: Chronic renal dysfunction may develop after pediatric heart
      transplantation (PHTx). We examined the incidence of end-stage renal disease
      (ESRD) and chronic renal insufficiency (CRI) after PHTx, the associated pre
      transplant patient characteristics, and impact of renal disease on survival.
      METHODS: Data sources included the Scientific Registry of Transplant Recipients,
      Centers for Medicare and Medicaid Services and the Social Security Death Master
      File. All PHTx recipients (age <18 years) in the USA from 1990 to 1999 who
      survived >1 year were included. ESRD was defined as long-term dialysis and/or
      kidney transplant. CRI was defined as creatinine >2.5 mg/dl, including those with
      ESRD. Relationships between pre-transplant characteristics and time to ESRD and
      CRI were analyzed using Cox proportional hazards models. The effect of renal
      disease on survival was analyzed using time-dependent Cox models. RESULTS: During
      the mean follow-up of 7 years (range 1 to 14 years), 61 of 2,032 (3%) PHTxs
      developed ESRD. Ten-year actuarial risks for ESRD and CRI were 4.3% and 11.8%,
      respectively. In a multivariate analysis, significant risk factors for ESRD were:
      hypertrophic cardiomyopathy; African-American race; intensive care unit (ICU)
      stay or extracorporeal membrane oxygenation (ECMO) at time of transplant; and pre
      transplant diabetes. Risk factors for CRI were: pre-transplant dialysis;
      hypertrophic cardiomyopathy; African-American race; and previous transplant.
      Adjusted risk of death in those who developed CRI was 9-fold higher than in those
      who did not (p < 0.0001). CONCLUSIONS: After PHTx there is an increasing risk for
      CRI and ESRD over time. Recipients with the characteristics identified in this
      study may be at greater risk. Development of renal disease significantly
      increases the risk of post-transplant mortality.

PMID- 17449415
TI  - Outcomes after lung transplantation in patients with chronic hepatitis C virus
      infection.
AB  - BACKGROUND: Hepatitis C virus (HCV) infects 4 million people in the USA, with a
      prevalence of 1.4%. The seropositivity rate among potential lung transplant
      candidates is 1.9%, yet little information is available regarding outcomes of
      lung transplantation in HCV-positive lung transplant recipients. Our study
      reports outcomes of lung transplantation in HCV-positive recipients and compares
      them to HCV-negative controls. METHODS: A retrospective analysis of the Cleveland
      Clinic Foundation's lung transplant database (465 patients) identified six HCV
      positive patients. Demographic data, etiology of HCV infection, HCV viral load
      pre- and post-transplant, pre-transplant hepatic pathology, serial transaminases,
      incidence of acute hepatitis, graft function data and patient survival data were
      obtained by chart extraction. RESULTS: Five HCV-positive recipients had a pre
      transplant liver biopsy, none of whom had evidence of cirrhosis pre-transplant.
      Although HCV RNA levels markedly increased post-transplant, no concomitant
      increase in transaminases was noted. There was no significant difference in the
      incidence of acute rejection at 1 year in our HCV-positive cohort compared with
      the HCV-negative lung transplant recipients from our institution. One patient
      developed bronchiolitis obliterans syndrome (BOS) during the follow-up period.
      Two patient deaths occurred, one at 8 months and the other at 2 years post
      transplant. No evidence of hepatic dysfunction was noted in either deceased
      patient. The four surviving patients are alive at a median 3.2 years (range 1 to
      6 years). CONCLUSIONS: No significant difference in patient or graft survival was
      noted between the HCV-positive lung transplant recipients and the HCV-negative
      recipients.

PMID- 17449416
TI  - Extracorporeal membrane oxygenation for primary graft dysfunction after lung
      transplantation: analysis of the Extracorporeal Life Support Organization (ELSO)
      registry.
AB  - BACKGROUND: Some patients with severe primary graft dysfunction (PGD) after lung
      transplantation (LTx) require gas exchange support using an extracorporeal
      membrane oxygenator (ECMO) as a life-saving therapy. A few single-center
      experiences have been reported with relatively few cases of ECMO after LTx.
      METHODS: We reviewed outcomes of ECMO in lung transplant recipients included in
      the Extracorporeal Life Support Organization (ELSO) registry, which was
      established with the intention to improve quality and outcome of extracorporeal
      life support (ECLS) in patients treated with ECMO applied for all indications.
      RESULTS: The ELSO registry currently includes 31,340 ECMO cases, of which 151
      were post-LTx patients with primary graft dysfunction (PGD). The mean age was 35
      +/- 18 years. Indications for LTx were acute respiratory distress syndrome,
      (15%), cystic fibrosis (15%), idiopathic pulmonary fibrosis (8%), primary
      pulmonary hypertension, (10%), emphysema (15%), acute lung failure (11%), other
      (23%), and unknown (3%). ECMO run time was 140 +/- 212 hours. Venovenous ECMO was
      used in 25, venoarterial in 89, and other modes in 15 patients (unknown in 22).
      ECMO was discontinued in 93 patients owing to lung recovery. It was also
      discontinued in 29 patients with multiorgan failure, in 22 patients that died
      with no further specification, and in 7 patients for other reasons. In total, 63
      (42%) patients survived the hospital stay. Major complications during ECMO
      included hemorrhage (52%), hemodialysis (42%), neurologic (12%), and cardiac
      (28%) complications, inotropic support (77%), and sepsis (15%). CONCLUSIONS:
      Although the ELSO registry was not primarily established to study ECMO in LTx, it
      provides valuable insights and evidence that there is indeed an appreciable
      salvage rate with the use of ECMO for PGD after LTx. Clearly, this is a very high
      risk patient population, and no single center can accumulate a large experience
      of ECMO for this specific indication. These data, however, underscore the
      importance of developing a specific registry for patients put on ECLS devices so
      that we can better study the outcomes, determine optimum treatment strategies,
      and optimize patient and device selection, and thus improve the outcomes of
      patients requiring this unique therapy.

PMID- 17449417
TI  - Analysis of cardiac dimensions, mass and function in heart transplant recipients
      using 64-slice multi-detector computed tomography.
AB  - BACKGROUND: Heart transplant recipients present a challenge to cardiac multi
      detector computed tomography (MDCT) imaging due to high resting heart rates and
      body mass indices. Previous studies demonstrated the feasibility of coronary
      allograft vasculopathy detection by MDCT in heart transplant recipients. However,
      its performance in assessing cardiac structure and function in these patients has
      not been evaluated. The aim of this study was to compare 64-slice MDCT analysis
      of cardiac structure and function to 2-dimensional echocardiography in heart
      transplant recipients. METHODS: Two independent observers used both semi
      automated and automated software to measure chamber dimensions and left
      ventricular ejection fraction and mass in 20 heart transplant recipients by 64
      slice MDCT. Inter-observer variability was determined. The results were compared
      with echocardiographic measurements provided by another blinded observer.
      RESULTS: There was moderate agreement between MDCT and echocardiography for
      chamber dimension measurements, except for left atrial diameter. Ejection
      fraction by MDCT was slightly lower (mean difference: -2 +/- 9%, p = 0.29) than
      that obtained by echocardiography and the correlation was moderate (R = 0.49 to
      0.54). Left ventricular mass measurements were significantly lower by MDCT (mean
      difference: -87 +/- 44 g, p < 0.001). Inter-observer agreement for MDCT analysis
      of left ventricular function (R = 0.90) and mass (R = 0.83) were excellent.
      CONCLUSIONS: These findings demonstrate moderate agreement between 64-slice MDCT
      and echocardiography in the assessment of chamber dimensions as well as left
      ventricular mass and function in heart transplant recipients with low inter
      observer variability. Also, the addition of cardiac structural and functional
      analysis to MDCT coronary angiography requires no additional scan time, contrast
      administration or radiation exposure.

PMID- 17449418
TI  - Inhibition of chemokine receptor CCR2 and CCR5 expression contributes to
      simvastatin-induced attenuation of cardiac allograft vasculopathy.
AB  - BACKGROUND: Accumulating evidence reveals that statins possess pleiotropic
      properties beyond cholesterol reduction, which may contribute to the attenuation
      of cardiac allograft vasculopathy (CAV). Recent in vitro data suggest that
      statins could down-regulate chemokine receptors. This study was designed to test
      the hypothesis that simvastatin ameliorates CAV development via the inhibition of
      chemokine receptor expression in an inbred rat model of cardiac transplantation.
      METHODS: Animals were divided into four groups: isograft; control (cyclosporine
      [CsA] + vehicle); low-dose simvastatin (LSIM; CsA + 5 mg/kg simvastatin); and
      high-dose simvastatin (HSIM; CsA + 10 mg/kg simvastatin). Donor hearts from
      Fisher 344 rats were transplanted heterotopically into Lewis rat recipients. CsA
      was administered at 1.5 mg/kg/day for 2 weeks post-operatively. In addition,
      recipients were treated daily with simvastatin or vehicle for 8 weeks. Donor
      hearts were harvested for histopathologic and immunohistochemical examination.
      Intragraft concentration of chemokines and chemokine receptor expression were
      analyzed using enzyme-linked immunosorbent assay and quantitative real-time
      polymerase chain reaction, respectively. RESULTS: Both low and high doses of
      simvastatin significantly decreased the CAV score; inhibited recruitment of T
      lymphocytes and macrophages; reduced levels of intragraft MCP-1 (monocyte
      chemoattractant protein-1), RANTES (regulated on activation, normal T-cell
      expressed and secreted) protein and IP-10 (interferon-inducible protein-10); and
      down-regulated expression of chemokine receptors CCR2 and CCR5. CXCR3 expression
      was not affected by simvastatin treatment. CONCLUSIONS: Our results demonstrate
      that simvastatin may attenuate CAV development, possibly through retarding
      intragraft chemokine accumulation and chemokine receptor expression.

PMID- 17449419
TI  - Alterations in the fibrinolytic cascade post-transplant: evidence of a bimodal
      expression pattern.
AB  - BACKGROUND: Changes in the fibrinolytic system that occur after cardiac
      transplantation (CTx) and the factors that influence such changes have been
      poorly described, yet may be important in determining the varying morphologic
      features of transplant-related coronary artery disease (TxCAD). METHODS: Baseline
      demographic as well as serial clinical information and plasma fibrinolytic levels
      were prospectively recorded pre-CTx and at multiple time-points post-CTx in 110
      de novo cardiac transplant recipients. RESULTS: We noted a biphasic change in
      fibrinolytic activity over the first year of CTx with an early immediate decline
      in plasminogen activator inhibitor-1 (PAI-1) activity (p > 0.001) matched with
      stable PAP (plasmin) activity corresponding to an "enhanced" fibrinolytic state
      early post-CTx. This was followed by a significant increase at 6 months (p =
      0.004) and 1 year (p < 0.001) in PAI-1 activity concomitant with a significant
      decline in PAP after 3 months (p = 0.005 at 3 months, p < 0.001 at 6 months, p <
      0.001 at 1 year) corresponding to an "impaired" fibrinolytic state late post-CTx.
      CONCLUSION: The biphasic nature of the fibrinolytic system observed herein may
      account for the varying morphologic features of TxCAD.

PMID- 17449420
TI  - Elevated uric acid levels predict allograft vasculopathy in cardiac transplant
      recipients.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) poses the greatest threat to the
      long-term survival of cardiac transplant recipients, and these individuals often
      exhibit elevated levels of uric acid (UA), a stimulator of T cells. We
      hypothesized that hyperuricemia is associated with CAV in cardiac transplant
      recipients. METHODS: UA levels were measured in cardiac transplant recipients
      between January 2003 and January 2005. Surveillance cardiac catheterizations
      performed 3 months to 1 year after UA measurement were reviewed. The relationship
      between UA and CAV was adjusted for possible confounders with propensity scores
      and confirmed with goodness-of-fit tests. RESULTS: The 105 patients included in
      this study were a median 63.3 months post-transplant and their left heart
      catheterizations were performed a median 5.6 months after UA measurement. Focal
      stenosis was evident in 25 angiograms and 31 showed distal pruning of the
      coronary arteries. Compared with the lowest quartile of UA, the highest quartile
      had an increased risk of CAV: odds ratio (OR) 6.11 (95% CI 1.47 to 25.5; p =
      0.013) for focal stenosis and OR 4.60 (95% CI 1.34 to 15.8; p = 0.015) for distal
      pruning. After adjustment, this relationship persisted for both focal stenosis
      (OR 5.53, 95% confidence interval [CI] 1.29 to 23.7; p = 0.021) and distal
      pruning (OR 4.21, 95% CI 1.15 to 15.4; p = 0.029). CONCLUSIONS: Elevated UA
      confers an increased risk of CAV. This association may be causal, with
      pathophysiologic implications for the role of hyperuricemia in allograft failure
      and, if substantiated, could have clinical implications for the use of xanthine
      oxidase inhibitors in cardiac transplant recipients.

PMID- 17449421
TI  - A randomized, controlled trial of daclizumab vs anti-thymocyte globulin induction
      for lung transplantation.
AB  - BACKGROUND: Rejection remains a significant cause of morbidity and mortality
      after lung transplantation. The purpose of this study was to test the efficacy
      and safety of daclizumab (DZM) vs anti-thymocyte globulin (ATG) as a component of
      induction therapy. METHODS: Fifty adults undergoing lung transplantation were
      randomized to receive either ATG or DZM during induction therapy. Patients were
      followed for 1 year after transplant. RESULTS: Although there was no significant
      difference in the number of acute or chronic rejections between groups, there was
      a trend toward a delay in time to first acute rejection with DZM induction.
      Average absolute lymphocytes and average platelet count were significantly higher
      in the DZM group. Cytomegalovirus (CMV) serology mismatch was higher in the DZM
      group (7 vs 1, p = 0.05). The DZM group had a greater number of infections (83 vs
      47, p = 0.02); however, the number of CMV infections was also significantly
      greater (18 vs 6, p = 0.03), corresponding to a higher incidence of CMV mismatch.
      A cost analysis revealed no difference between total drug costs, intensive-care
      unit (ICU) costs and total hospital costs. One-year survival was 96% in the DZM
      group and 88% in the ATG group. CONCLUSIONS: DZM is a safe component of induction
      therapy in lung transplantation. In addition, DZM may prolong freedom from acute
      rejection. Significant infections were more frequent in the DZM group, but this
      was likely due to a higher incidence of CMV mismatch. Both methods of induction
      therapy worked well, with excellent 1-year survival.

PMID- 17449422
TI  - Successful management of antibody-mediated cardiac allograft rejection with
      combined immunoadsorption and anti-CD20 monoclonal antibody treatment: case
      report and literature review.
AB  - Chronic rejection is still the major limitation of long-term outcome of heart
      transplant recipients. Several recent studies demonstrated that a not negligible
      proportion of chronic allograft rejection episodes are not only mediated by T
      cell response but also triggered by pre-transplant and de novo post-transplant
      donor-specific alloantibodies. This points at a fundamental role of humoral
      immune response mechanisms that contribute to early and late graft failure. This
      type of rejection is an unsolved problem solid organ transplantation because
      current immunosuppressive regimens are generally intended to interfere in T-cell
      signalling pathways. Various options for the removal of circulating
      alloantibodies and the prevention of alloantibody formation by B-cell depletion
      have been described. Nevertheless, effective standardized schemes for the
      treatment of antibody-mediated graft rejection have to be defined. We present a
      heart transplant recipient with sustained antibody-mediated graft rejection who
      was successfully managed with a combination treatment consisting of 3 cycles of
      immunoadsorption and a single-dose administration of the anti-CD20 monoclonal
      antibody rituximab.

PMID- 17449423
TI  - N-terminal prohormone brain natriuretic peptide as a marker for detecting low
      functional class patients and candidates for cardiac transplantation: linear
      correlation with exercise tolerance.
AB  - BACKGROUND: N-terminal prohormone brain natriuretic peptide (NT Pro BNP) plasma
      levels have been associated with indices of left ventricular (LV) function and
      aerobic capacity in heart failure. The aim of our study was to use NT Pro BNP for
      the prediction of low functional class patients and also to detect candidates for
      cardiac transplantation. METHODS: We studied 100 patients with impaired left
      ventricular (LV) function. Mean LV ejection fraction (LVEF) was 35% +/- 9%. Blood
      samples for NT Pro BNP assessment were taken at baseline during treadmill
      exercise testing. LV cavity diameters, left atrial size, and LVEF were measured
      by echocardiography. RESULTS: Plasma levels of NT Pro BNP correlated
      significantly with peak oxygen consumption (VO(2)) values (r = -0.77, p < 0.001).
      LVEF correlated well with NT Pro BNP (r = -0.67, p < 0.001). NT Pro BNP plasma
      levels correlated strongly with New York Heart Association functional class (r =
      0.70, p < 0.001). NT Pro BNP values exceeding 335 pg/ml showed 83% sensitivity
      and 76% specificity for detecting VO(2) values below 20 ml/kg/min (area under the
      curve [AUC] = 86%, p < 0.001). NT Pro BNP plasma levels exceeding 1,190 pg/ml
      showed 83% sensitivity and 86% specificity for detecting VO(2) of less than 14
      ml/kg/min (AUC = 90%, p < 0.001). NT Pro BNP plasma levels exceeding 1,610 pg/ml
      showed 87% sensitivity and specificity 82% for detecting VO(2) of less than 10
      ml/kg/min (AUC = 90%, p < 0.001). NT Pro BNP plasma levels exceeding 680 pg/ml
      showed 91% sensitivity and 73% specificity for detecting LVEF of less than 28%
      (AUC = 86%, p < 0.001). CONCLUSIONS: NT Pro BNP plasma levels correlate both with
      LVEF and aerobic capacity, can predict low functional cardiopulmonary exercise
      capacity in patients with impaired left ventricular function, and are useful for
      detecting candidates for cardiac transplantation.

PMID- 17449424
TI  - Beta-adrenergic receptor antagonism preserves myocardial function after brain
      death in a porcine model.
AB  - BACKGROUND: Cardiac dysfunction after brain death decreases the already limited
      number of potential donors for cardiac transplantation. Acute beta-adrenergic
      receptor (betaAR) desensitization after the brain death-associated catecholamine
      surge is an important mechanism. We hypothesized that acute betaAR antagonism
      could improve myocardial function after brain death by preserving betaAR
      signaling. METHODS: Pigs were randomly assigned to three study groups (n = 5):
      sham; brain death; and brain death with betaAR antagonist (200 microg/kg/min
      esmolol), 30 minutes before brain death until 45 minutes after brain death.
      Functional data were collected for 6 hours after brain death and tissues
      procured. RESULTS: Compared with baseline, pre-load recruitable stroke work
      (PRSW), a pre-load-independent measure of systolic function (21.4 +/- 7.5 vs 43.3
      +/- 6.8, slope of regression line during vena caval occlusion, p < 0.001),
      diastolic function (Tau, 101 +/- 54.7 vs 36.4 +/- 5.4 ms, p = 0.03) and systemic
      oxygen delivery (151 +/- 79.7 vs 298 +/- 78.7 ml/min, p < 0.001) deteriorated in
      untreated animals at 6 hours after brain death. In contrast, betaAR antagonist
      maintained baseline systolic function (PRSW, 37.8 +/- 5.6 vs 38.2 +/- 4.7, slope
      of regression line during vena caval occlusion, p = 0.92), diastolic function
      (Tau, 32.6 +/- 5.1 vs 48.5 +/- 28.3 ms, p = 0.57) and oxygen delivery (427 +/-
      116 vs 397 +/- 98.8 ml/min, p = 0.36) at 6 hours after brain death. betaAR
      antagonist preserved betaAR signaling, as demonstrated by similar left
      ventricular (LV) basal (55.4 +/- 32.8 vs 58.8 +/- 10.9 pmol/mg/min, p = 0.40) and
      isoproterenol-stimulated (125 +/- 70.5 vs 124 +/- 52.0 pmol/mg/min, p = 0.49)
      adenylate cyclase activity at 6 hours after brain death, upon comparing betaAR
      antagonist and sham treatment groups. Both LV basal and isoproterenol-stimulated
      adenyl cyclase activity were higher with betaAR antagonist (25.9 +/- 4.8
      pmol/mg/min, p = 0.03) than with untreated brain death (55.6 +/- 17.3
      pmol/mg/min, p = 0.02). CONCLUSIONS: Beta-adrenergic receptor antagonism before
      brain death preserves cardiac function by preventing betaAR desensitization. This
      therapy in potential donors might increase the number of organs available for
      transplantation.

PMID- 17449425
TI  - Results of clinical lung transplant from uncontrolled non-heart-beating donors.
AB  - BACKGROUND: The scarcity of grafts for lung transplant and the growing number of
      candidates expecting an organ has led to an increase of deaths in patients
      waiting for lung transplantation. Non-heart-beating donors (NHBD) represent a
      promising source of grafts for those who are involved in clinical lung
      transplantation. We present the results of our series of 17 out-of-hospital NHBD
      lung transplantations performed since 2002. METHODS: We have collected data from
      17 donors and recipients involved in NHBD lung transplants since 2002, as well as
      data referring to the type of procedure and peri-operative events. We describe
      the incidence of post-operative complications with special attention to primary
      graft disfunction (PGD), bronchial healing, bronchiolitis obliterans syndrome
      (BOS), and survival. We used Kaplan-Meier method to obtain the survival curve.
      RESULTS: G2-G3 PGD was reported in 9 patients (53%), with a complete restoration
      of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio in
      170 hours for G2 and 168 hours for G3. There were no deaths directly related to
      PGD. Acute rejection was detected in 7 patients (41%), 4 of which exceeded grade
      1. The incidence of BOS after transplantation was 1 (7%) of 14 patients during
      the first year, 2 (11%) of 9 in the second year, and 2 (50%) of 4 in the third
      year. Hospital mortality rate was 17%. The survival rates were 82% at 3 months,
      69%, at 1 year, and 58% at 3 years. CONCLUSIONS: Mid-term results confirm the
      adequacy of uncontrolled NHBD as a promising complementary source of lung donors
      for clinical transplant.

PMID- 17449427
TI  - Getting old with a new heart: impact of age on depression and quality of life in
      long-term heart transplant recipients.
AB  - BACKGROUND: Limited research has been done on depression and quality of life in
      long-term survival after heart transplantation. The aim of the present study was
      to investigate the role of age on depression and quality of life in a sample of
      long-term heart transplant recipients. METHODS: We investigated 137 consecutive
      patients recruited in a single center who were still alive at more than 10 years
      after transplantation. Quality of life and depression were rated with the Medical
      Outcome Study Short Form (SF-36) and the Beck Depression Inventory (BDI),
      respectively. Sociodemographic, clinical, affective, and quality of life data for
      long-term survival patients stratified by current age younger than 70 years
      (young) and 70 years or older (old) were compared using Fisher's exact tests and
      Student's t-tests. RESULTS: The SF-36 Mental Component Summary did not
      significantly differ between the young subjects (48.75 +/- 10.2) compared with
      old (48.47 +/- 10.1; p = 0.897). By contrast, the SF-36 Physical Component
      Summary was higher in younger subjects (46.88 +/- 10.2 vs 40.81 +/- 10.6, p =
      0.008). According to BDI, 37.4% of the young group and 13.3% of the old group
      scored above the selected threshold of 10 (p = 0.014). CONCLUSIONS: In the light
      of our findings, older age does not seem to negatively affect the mental
      component of quality of life in the long term after heart transplantation, but it
      does on the physical component, as expected. On the other hand, it may be even
      associated with a lower prevalence of depressive symptoms more than 10 years
      after surgery. Hence, age per se does not represent a major limiting factor when
      considering candidates for this procedure, at least with regard to the issue of
      psychologic distress.

PMID- 17449426
TI  - Patterns and predictors of quality of life at 5 to 10 years after heart
      transplantation.
AB  - BACKGROUND: Although studies have provided us with a cross-sectional analysis of
      long-term quality of life (QOL) after transplantation, relatively few
      longitudinal studies have been done that allow us to understand changes in QOL
      over time. The purposes of our study were to describe QOL over time and identify
      predictors of QOL longitudinally from 5 to 10 years after heart transplantation.
      METHODS: All 555 subjects enrolled in this study completed booklets of
      questionnaires. These patients had a mean age of approximately 54 years (range 21
      to 75 years) at time of transplant. Seventy-eight percent were men and 88% were
      white. Participants completed nine self-report QOL instruments for this study.
      Statistical analyses included frequencies, means +/- standard deviations (plotted
      over time), Pearson correlation coefficients and multiple regression coupled with
      repeated measures. RESULTS: At 5 to 10 years after heart transplantation,
      recipients reported high levels of satisfaction with overall QOL and with health
      related QOL, which was stable over the 5-year period. Predictors of satisfaction
      with overall QOL (that individually accounted for 1% variance or more) were
      primarily psychosocial variables (overall model explaining 71% of variance),
      whereas predictors of satisfaction with QOL related to health and functioning
      (that also explained > or =1% variance) included symptom distress and physical
      function, as well as psychosocial variables (overall model explaining 72% of
      variance). CONCLUSIONS: At 5 to 10 years after heart transplantation, QOL
      remained positive and stable. Bio-psychosocial variables predicted satisfaction
      with overall QOL and health-related QOL. Understanding of these bio-psychosocial
      variables provides direction for the development of long-term therapeutic
      strategies after heart transplantation so that patients can have good post
      transplant outcomes.

PMID- 17449428
TI  - Diabetic myonecrosis in an orthotopic heart transplant recipient.
AB  - Diabetic myonecrosis or muscle infarction (DMI) is a rare cause of lower
      extremity pain that usually occurs in patients with poorly controlled diabetes.
      Although most patients recover with opiate analgesics and anti-inflammatory
      medications, this type of myonecrosis is associated with the presence of serious
      vascular disease. Consideration of this diagnosis and use of soft-tissue imaging
      are especially important in diabetic organ transplant recipients to prevent
      erroneous treatment for presumed infection. We describe what we believe is the
      first reported case of diabetic myonecrosis occurring in a patient with
      iatrogenically induced diabetes after orthotopic heart transplantation.

PMID- 17449429
TI  - Successful fibrinolysis after acute left ventricular assist device thrombosis.
AB  - The Berlin Heart INCOR system (Berlin Heart AG, Berlin, Germany) is a left
      ventricular assist device that generates a laminar blood flow. One of our INCOR
      implanted patients was admitted to the hospital with clinical data indicating
      device thrombosis. The flow through the pump was assessed by contrast injection
      into the inflow canula. Lack of flow through the pump was found. A decision was
      made to perform fibrinolysis, which was performed by a reteplase injection into
      the device's inflow canula. After the manipulation, a restoration of the flow
      through the pump was observed. The patient was discharged 9 days after the
      procedure with no complications.

PMID- 17449430
TI  - Diastolic, but not systolic blood pressure at admission predicted long-term
      mortality in acute cardiogenic pulmonary edema.

PMID- 17449431
TI  - Diagnosis and classification of pelvic girdle pain disorders, Part 2:
      illustration of the utility of a classification system via case studies.
AB  - Pelvic girdle pain (PGP) disorders are complex and multi-factorial and are likely
      to be represented by a series of sub-groups with different underlying pain
      drivers. Both the central and peripheral nervous systems have the potential to
      mediate PGP disorders. Even in the case of a peripheral pain disorder, the
      central nervous system can modulate (to promote or diminish) the pain via the
      forebrain (cognitive factors). It is hypothesised that the motor control system
      can become dysfunctional in different ways. A change in motor control may simply
      be a response to a pain disorder (adaptive), or it may in itself promote abnormal
      tissue strain and therefore be 'mal-adaptive' or provocative of a pain disorder.
      Where a deficit in motor control is 'mal-adaptive' it is proposed that it could
      result in reduced force closure (deficit in motor control) or excessive force
      closure (increased motor activation) resulting in a mechanism for ongoing
      peripheral pain sensitisation. Three cases are presented which highlight the
      multi-dimensional nature of PGP. These cases studies outline the practical
      clinical application of a classification model for PGP and the underlying
      clinical reasoning processes inherent to the application of this model. The case
      studies demonstrate the importance of appropriate classification of PGP disorders
      in determining targeted intervention directed at the underlying pain mechanism of
      the disorder.

PMID- 17449432
TI  - Diagnosis and classification of pelvic girdle pain disorders--Part 1: a mechanism
      based approach within a biopsychosocial framework.
AB  - The diagnosis and classification of pelvic girdle pain (PGP) disorders remains
      controversial despite a proliferation of research into this field. The majority
      of PGP disorders have no identified pathoanatomical basis leaving a management
      vacuum. Diagnostic and treatment paradigms for PGP disorders exist although many
      of these approaches have limited validity and are uni-dimensional (i.e.
      biomechanical) in nature. Furthermore single approaches for the management of PGP
      fail to benefit all. This highlights the possibility that 'non-specific' PGP
      disorders are represented by a number of sub-groups with different underlying
      pain mechanisms rather than a single entity. This paper examines the current
      knowledge and challenges some of the common beliefs regarding the sacroiliac
      joints and pelvic function. A hypothetical 'mechanism based' classification
      system for PGP, based within a biopsychosocial framework is proposed. This has
      developed from a synthesis of the current evidence combined with the clinical
      observations of the authors. It recognises the presence of both specific and non
      specific musculoskeletal PGP disorders. It acknowledges the complex and
      multifactorial nature of chronic PGP disorders and the potential of both the
      peripheral and central nervous system to promote and modulate pain. It is
      proposed that there is a large group of predominantly peripherally mediated PGP
      disorders which are associated with either 'reduced' or 'excessive' force closure
      of the pelvis, resulting in abnormal stresses on pain sensitive pelvic
      structures. It acknowledges that the interaction of psychosocial factors (such as
      passive coping strategies, faulty beliefs, anxiety and depression) in these pain
      disorders has the potential to promote pain and disability. It also acknowledges
      the complex interaction that hormonal factors may play in these pain disorders.
      This classification model is flexible and helps guide appropriate management of
      these disorders within a biopsychosocial framework. While the validity of this
      approach is emerging, further research is required.

PMID- 17449433
TI  - Dependence receptors: when apoptosis controls tumor progression.
AB  - A novel way of seeing cellular receptors has recently emerged. While a receptor
      used to be considered as inactive until bound by its ligand, it has been proposed
      that some receptors may also be active in the absence of their ligand. These so
      called dependence receptors induce a specific death signal when the ligand is
      absent from the cell: Therefore, the expression of one of these receptors leads
      to the cell becoming dependent on the presence of the ligand for its survival. We
      have hypothesized that such a trait is a mechanism that allows inhibition of
      tumor growth, by inducing apoptosis "abnormal" cells that would usually grow in
      settings of ligand unavailability, i.e. local growth of tumor cells or growth
      beyond primary tumor site. Along this line, back in the early 90s, Vogelstein and
      colleagues suggested that a gene called DCC (for deleted in colorectal cancer)
      could be a tumor suppressor gene because it was found to be deleted in more than
      70% of colorectal cancers, as well as in many other cancers. During the last
      fifteen years, controversial data have failed to firmly establish whether DCC is
      indeed a tumor suppressor gene. However, our observation that DCC behaves as a
      dependence receptor that induces cell death unless its ligand netrin-1 is
      present, together with the fact that mice engineered to block DCC-induced cell
      death by overexpressing netrin-1 are predisposed to develop colorectal tumors,
      strengthen the role of dependence receptors as tumor suppressors. In this review,
      we will describe the implication of the netrin-1/receptor pairs as novel negative
      regulators of tumor development.

PMID- 17449434
TI  - [Adolescents and cancer, a new field of research supported by the national league
      against cancer].

PMID- 17449435
TI  - [Cancer incidence and survival among adolescents and young adults in France (1978
      1997)].
AB  - Malignancies are rare young French adults but represent the third significant
      cause of death in the cohort of 15-24 years of age. The aim of this study was to
      investigate incidence and survival rates of French adolescents and young adults
      with cancer. All cases of cancer occuring over a 20-year period (1978-1997) in
      the cohort of patients aged 15 to 24, were obtained from nine population-based
      registries (10 % of the French population). Basal cell carcinomas of the skin
      were excluded. 1161 and 1884 cases were recorded in adolescents and young adults,
      respectively. Overall incidence rates (IR) were 161.4/10(6) in adolescents aged
      15-19 years (M/F ratio = 1.3), and 252.6/10(6) in young adults aged 20-24 years
      (M/F ratio : 1.2). During the 1978-97 period, the IRs appeared stable over the
      years, +0.4 % [CI95 % = -2.3 ; +3.1] (p = 0.79) for adolescents and +1.7 % [CI95
      % = -4.0 ; +7.3] (p = 0.57) for young adults. Five-year overall survival rates
      were 69.1 % [CI95 % = 66.4-71.8] for adolescents and 74.5 % [CI95 % = 72.3-76.7]
      for young adults. The 5-year survival rate for patients 15-24 years improved from
      62.0 % (CI95 % = 57.5-66.5) in 1978-82 to 80.2 % (IC95 % = 77.7-82.8) in 1993-97.
      Noteworthy, results in adolescents and young adults are poor compared to the ones
      from their younger counterparts, especially in patients with acute lymphoblastic
      leukemia, non-Hodgkin lymphoma, Ewing's sarcoma, osteosarcoma, rhabdomyosarcoma,
      and astrocytoma. Further studies are warranted to elucidate whether these
      differences are due to intrinsic biological properties of the tumor or to
      differences in clinical practices in the two populations.

PMID- 17449436
TI  - [Non Hodgkin's lymphoma in adolescents].
AB  - In France, adolescents (15-20 years) with non Hodgkin's lymphoma (NHL) are
      referred either to paediatric or to adult onco-haematological departments.
      According to data obtained from regional tumour registries (covering about 10% of
      France), their 5 year survival rate was 59% whereas it was 87% for children (< or
      =14 years) treated for NHL during a similar period of time. We reviewed the
      management of NHL either by the paediatricians or the onco-hematologists for
      adults. The categories of NHL that are reviewed and whose clinical and biological
      characteristics are presented are: Burkitt, lymphoblastic and large cell, either
      B or anaplastic. This review shows that, in most series, outcome was better in
      children than in adults. This raises the reasons of this difference: is it due to
      the different therapeutic approaches, to different tolerance of chemotherapy, to
      different biology within the same histological type ? Further studies specific to
      the adolescents are needed to better know the biology of their lymphoma and to
      determine the best therapeutic approach.

PMID- 17449437
TI  - [Compliance to treatment of adolescents with cancer].
AB  - Compliance is a very important issue in medicine for three major reasons. Non
      compliance has a considerable financial cost for health care systems. Adherence
      to treatment is the main link between intention to treat and the desired health
      outcome. Finally, the influence of non-compliance on the conclusions of clinical
      research trials can have severe consequences. Despite the importance of these
      issues, our literature review found very few recent studies concerning the
      compliance of adolescents with cancer. Non-compliance has many causes. The
      relationship between patient and health care team, the organisational aspects of
      care and the youth's perception of his/her illness and its treatment all
      significantly affect adolescents'compliance. The influence of the treatment on
      young people's lifestyles as well as the physical transformations induced by the
      treatment are also important factors, due to adolescents desire to conform to
      their peer group. Family relationships also play a significant part in
      adolescents'therapeutic adherence. Since the end of the 1990s, research on
      adherence has focused more on the importance of the doctor-teenager relationship
      and the strong influence of the patients'perception concerning health in general
      and his/her illness in particular. Negotiation is an essential component of a
      successful treatment in teenagers due to their increasing desire for autonomy.
      Despite numerous recommendations international research has not succeeded in
      using standardised terms concerning compliance to treatment regimens or come to
      an agreement on valid assessment methods. Longitudinal studies should be carried
      out in order to determine causal links between factors and compliance in a
      methodologically correct manner. Research should be quantitative but must also
      include the conceptual elements which have been put forward by qualitative
      research, namely the importance of teenagers'point of view concerning their
      treatment.

PMID- 17449438
TI  - [Information for teenagers with cancer: current state in French pediatric
      oncology units].
AB  - In France, teenagers with cancer are managed mainly in paediatric units, given
      that there are only few teenage cancer units. This situation leads to the
      following question: are teenagers with cancer provided with tailored patient
      education? The object of this study was to identify education programmes
      specifically designed for teenagers in French paediatric oncology units. This
      study was conducted first by questionnaires, second by interviews with health
      care providers in units where information programs had been implemented. Nine
      information programmes or projects were identified: 2 booklets, one log book, one
      Web chat, one video, one DVD, one educative muppet, one peer based education
      group project, one nursing education session project and one qualitative study
      project. Only 5 from these programmes or project were specifically designed for
      teenagers. Four approaches can be identified: conception of education materials,
      individual patient education, group patient education, informal patient
      education.

PMID- 17449439
TI  - [Adolescent confronting cancer and its place in the family].
AB  - Adolescent medicine is expanding in Europe with particular attention being given
      to cancer of adolescents and its treatment. At a time where specialised units for
      adolescents are being born, it is essential to collect the current knowledge on
      the pathological impact of the illness in this age period whose limits themselves
      are often blurred (13-21 years or 15-25 years). Adolescence is a transition
      between childhood and adulthood, during which one seeks psychological and
      emotional development. Cancer, by its direct repercussion on the adolescent and
      also by the disorganisation of the family, can involve risks impending the
      process of maturation and can also be a purveyor of psychological after-affects.
      The occurrence of the illness can isolate the adolescent and leak to a
      restriction of the psychological investment. The reality of possible death can
      hinder the ill adolescent from developing his natural opposition to the adults
      who represent authority such as parents or nurses, thereby hindering access to
      autonomy, independence and identity construction. One can find oneself locked in
      a state of trouble, confusion, becoming a stranger to oneself, with an impression
      of distance waxing between the young patient and others. The parents find
      themselves weakening and must make calls on their supporters. The siblings see
      their daily life becoming more unsettled and find themselves confronted by
      parents less available and reassuring. The impact on the brothers and sisters
      vary depending on their age and the capacity of the parent's adaptation. From the
      onset, adolescents struck by cancer necessitate an adaptation of the medical
      staff. The medical information, the treatment and the aid-care contracts must be
      approved by the adolescent himself but the parent's involvement remains
      essential. It is necessary to create an alliance of three. Conflicts and rivalry
      occur frequently between parents and the medical staff. One must study the
      possibility of creating a place adapted to care, with flexible surrounding,
      respecting the identity of the adolescent while supporting his educational or
      professional investments and his personal interests revolving around the exterior
      world. The psychological and social care must be accessible to all the family
      members. The terms and conditions of this psychological and material support are
      itemised.

PMID- 17449440
TI  - [Schooling of young people with cancer].
AB  - The schooling of young people with cancer poses various problems, similar to
      those experienced by disabled or chronically ill children. Published data on this
      subject in the medical literature comes mainly from studies carried out in the
      USA and the UK. Cancer and its treatment can cause both direct (learning
      difficulties or other disabilities...) and indirect (discrimination...) problems.
      Academic failure, and other problems linked to school absenteeism, can affect the
      future of adolescents with cancer. Sustaining schooling during the illness
      enables such patients to avoid falling behind academically, and to maintain his
      or her social status as a student. Due to the organisation of treatment regimes,
      education is provided in three environments : in hospital (during in-patient
      stays), at home (generally whilst the patient is convalescing), or at school.
      Paediatric oncologists have underlined the importance of establishing links
      between hospital and educational personnel (with parental approval), and suggest
      that a teachers'illness information manual should be produced. School re-entry is
      recommended as soon as possible. During the illness, the patient's presence in
      class is dependent on his or her general health, the progress of the cancer, and
      the treatment regime being followed. School absenteeism, inevitable during
      treatment periods and the year following diagnosis, is often associated with
      academic problems or failure. While many cancer patients worry about their school
      work and future educational progress, such problems remain rare. In the long
      term, the educational level of childhood or adolescent cancer survivors remains
      similar to that of the general population. In order to understand the issues
      surrounding the schooling of young cancer patients in France, long-term multi
      centre studies, focusing on adolescents, must be initiated.

PMID- 17449441
TI  - [Changes in chromosome number, genetic instability, and occupational exposures].
AB  - Aneugenic compounds cause chromosome missegregation during cell division and
      induce aneuploidy in cells that do not die. Aneuploidy is a key step in the
      progression from a normal cell into a cancerous cell, and it could represent an
      early event in the carcinogenic process. Missegregation of chromosome during
      anaphase often originates from centrosome abnormality, which plays a key role in
      the formation of the mitotic spindle during cell division. Micronuclei (MN) are
      thought to be biomarkers of chromosome damage due to genetic instability or
      exposure to environmental mutagens or carcinogens (occupational exposure for
      example). The MN assay in combination with fluorescent in situ hybridization
      discriminates between MN containing acentric chromosome fragments (chromosome
      breakage) and MN containing whole chromosomes (chromosome loss), consecutively to
      clastogenic and aneugenic events, respectively. Centromere-positive micronuclei
      are due to alteration in mitotic apparatus proteins. Two pathways could be
      involved : chromosome migration impairment would lead to MN containing a single
      chromosome whereas centrosome amplification would induce MN containing several
      chromosomes. For biomonitoring purposes, numerous confounding factors (host
      factors, lifestyle, genetic polymorphism) influence the MN biomarker. Thus, the
      separated analysis of MN containing a single or several centromeres could be
      useful, as centrosome abnormalities seem to be linked with an increase in genetic
      instability.

PMID- 17449442
TI  - [New tools in adjuvant breast cancer radiotherapy].
AB  - During the last century management of breast cancer became increasingly less
      aggressive for small tumors. Randomized trials demonstrated similar overall
      survival between mastectomy and breast-conservative surgery (BCS) followed by
      adjuvant radiation therapy (RT). BCS plus adjuvant RT +/- systemic therapy has
      become the standard of care for women with early breast cancer. Advances in
      modern RT technology allowed significant increase in high precision of target
      definition. Intensity modulated radiation therapy (IMRT) and gating, under
      investigation in miscellaneous cancers, are also in development for breast-cancer
      patients. These techniques decrease radiation toxicities and could be useful in
      the setting of concurrent use of RT and new systemic therapies such as
      trastuzumab. Another advance in RT is the development of accelerated partial
      breast irradiation (APBI) as a new concept in the adjuvant setting for early
      stage breast cancer. Intraoperative RT (IORT), immediate postoperative RT
      (interstitial brachytherapy or Mammosite device implantation) and delayed
      postoperative RT (external beam of photons or protons with 3D conformation) are
      under investigation. In this review, the role of modern whole breast irradiation
      is discussed, the rational of partial breast irradiation is argued and the
      different techniques are detailed.

PMID- 17449443
TI  - [Intraperitoneal chemotherapy in first-line combination treatment for advanced
      ovarian cancer].
AB  - The aim of intraperitoneal chemotherapy is to increase chemotherapy activity in
      exposing tumor to important cytotoxic drug concentration one to several logs
      greater with regional treatment. Intraperitoneal chemotherapy (IP) is given by
      infusion of the chemotherapeutic agent directly into the peritoneal cavity. This
      may increase the anticancer effect with fewer systemic adverse effects to
      comparison to intravenous therapy. In ovarian cancer, intraperitoneal
      chemotherapy has been used in second line treatment, in consolidation, and in
      first-line combination. The most recent trial conducted by the Gynecologic
      Oncology Group (GOG) study, a phase III randomised trial and reported by
      Armstrong et al. published in the New England Journal of Medecine in 2006,
      demonstrated that IP chemotherapy improves survival in patients with surgically
      treated ovarian cancer when added to intravenous therapy, compared with IV
      therapy alone. This study could change the standard treatment in advanced ovarian
      cancer. Despite increased toxic effects and the more complicated logistics of the
      drug administration, the data from GOG trial establish IP chemotherapy as an
      important advance in the first-line treatment of patients with optimally debulked
      stage III disease.

PMID- 17449444
TI  - [Erythropoietin levels in perioperative period in cancer patients].
AB  - Anemia is frequent in cancer patients, is the result of decreased erythropoietin
      production. In fact in cancer, alteration of immune system alters iron metabolism
      and inhibits erythropoietin production. In this study we proposed to determine
      the profile of erythropoietin secretion in anaemic cancer patients in the pre and
      postoperative period. Our prospective study from January to March 2005 included
      41 anemic cancer patients from 30 to 79 years old and 31 healthy individuals with
      iron deficiency anemia. A measure of erythropoietin, CRP, ferritin, iron levels
      and hemoglobin were released in healthy individuals and in cancer patients in
      preoperative period (J0) and postoperative period (J3, J8, J21). In preoperative
      period, the increase of serum erythropoietin was significantly lower in patients
      than in healthy individuals. In postoperative period, the levels of
      erythropoietin at J3 and hemoglobin's at J8 and J21 were significantly higher
      than in preoperative period (J0) (p < 0.05). In conclusion, despite the presence
      of inflammatory syndrome caused by surgery, cancer patients with anaemia increase
      their erythropoietin production in immediate postoperative period.

PMID- 17449446
TI  - Pharmacotherapy for schizophrenia and co-occurring substance use disorders.
AB  - Substance use disorder (SUD) occurs commonly in patients with schizophrenia and
      is associated with a poor outcome. Despite this common co-morbid occurrence (and
      its negative impact on the course of schizophrenia), there have been very few
      studies assessing pharmacological strategies for optimal treatment of these
      patients. A number of theories have been advanced to help explain the high rate
      of substance use disorder in patients with schizophrenia. Our group has suggested
      that the brain reward circuit dysfunction model, which may incorporate aspects of
      all of these models, may help direct research aimed at developing new
      pharmacological treatments for patients with schizophrenia and co-occurring SUD.
      Although typical antipsychotic medications appear to be of limited value in these
      patients, emerging, but preliminary, data suggest that the atypical
      antipsychotics, particularly clozapine, may be particularly helpful. The role of
      adjunctive medications, such as those medications that have recently been shown
      to be useful for the treatment of alcoholism, may have a role in the treatment of
      these patients, although only naltrexone has, thusfar, been carefully tested in
      these comorbid patients. Further studies are indicated to assess the role of
      novel pharmacologic treatment strategies for these patients. Ultimately, any
      medication given to these patients will need to be prescribed within psychosocial
      treatment programs aimed at assisting these patients in limiting and ultimately
      ceasing substance use.

PMID- 17449447
TI  - Modeling tardive dyskinesia: predictive 5-HT2C receptor antagonist treatment.
AB  - Tardive dyskinesia (TD), a movement disorder produced by long-term treatment with
      a classical antipsychotic drug, is generally considered to be a disorder of
      dopamine (DA) systems, since classical antipsychotics are potent DA D(2) receptor
      blockers. Also, acute DA D(1) agonist treatment of rats is known to produce
      vacuous chewing movements (VCMs), a behavioral feature resembling the oral
      dyskinesia that is so prominent in most instances of TD. In this paper we outline
      a series of studies in a new animal model of TD in which DA D(1) receptor
      supersensitivity was produced by neonatal 6-hydroxydopamine (6-OHDA) -induced
      destruction of nigrostriatal DA fibers. In rats so-lesioned 5-HT receptor
      supersensitivity is additionally produced, and in fact 5-HT receptor antagonists
      attenuate enhanced DA D(1) induction of VCMs. Moreover, in 6-OHDA-lesioned rats
      treated with haloperidol for one year, there a 2-fold increase in numbers of VCMs
      (vs intact rats treated with haloperidol); and this high frequency of VCMs
      persists for more than 6 months after discontinuing haloperidol treatment. During
      this stage, 5-HT(2) receptor antagonists, but not DA D(1) receptor antagonists,
      attenuate the incidence of VCMs. This series of findings implicates the 5-HT
      neuronal phenotype in TD, and promotes 5-HT(2) receptor antagonists, more
      specifically 5-HT(2C) receptor antagonists, as a rational treatment approach for
      TD in humans.

PMID- 17449449
TI  - From dopaminergic genes to psychiatric disorders.
AB  - Individual vulnerability to develop neurological and psychiatric disorders is
      associated with both genetic and environmental factors. Association studies in
      patients have explored the contribution of gene variants in the dopaminergic
      system in these disorders. This system is involved in motor control,
      endocrinological function, the reward system and cognition. The diverse
      physiological functions of dopamine are mediated by five different dopamine
      receptors, encoded by the genes DRD1, DRD2, DRD3, DRD4 and DRD5. These genes have
      various types of polymorphisms that can produce changes in the genetic product or
      expression levels. In recent years, the development of new technologies for
      genetic analysis, and a wider comprehension of the genetic sequences of these
      genes have increased our understanding of the implications of the dopaminergic
      system in both health and pathological states. It has also allowed the
      identification of genetic variants that may represent risk or protection factors
      for a variety of psychiatric disorders.

PMID- 17449448
TI  - Association in alcoholic patients between psychopathic traits and the additive
      effect of allelic forms of the CNR1 and FAAH endocannabinoid genes, and the 3'
      region of the DRD2 gene.
AB  - Little is known about the genetic factors that underlie the comorbidity between
      alcohol use disorder and antisocial personality disorder. Previous studies have
      associated both, dopaminergic and endocannabinoid systems to severe alcoholism
      with non-adaptive disrupted behaviours. In this work we have examined some gene
      variants involved in such systems in a sample of alcoholic patients to test
      whether there is a relationship with antisocial traits. The genetic analysis
      involved the genotyping of the single nucleotide polymorphism (SNP) TaqIA located
      nearby the DRD2 gene, the 10-repeat allele of a variable number tandem repeats
      (VNTR) of the SLC6A3 gene, the C385A FAAH SNP and the 3'-UTR microsatellite of
      CNR1 gene. The clinical study was performed in 137 Spanish alcohol dependent
      males. Antisocial Personality Disorder (DSM-IV) diagnosis was made by applying
      the International Personality Disorder Examination, and psychopathic traits were
      evaluated by the Hare's Psychopathy Checklist revised (PCL-R). The genotype
      distribution indicates there is a relationship between the TaqIA SNP, CNR1 and
      FAAH genes and PCL-R's Factor 1 in alcoholic patients. This relationship seems to
      be additive and independent and might be responsible for 11.4% of the variance in
      this PCL-R subscale. Our results suggest the implication of the dopaminergic and
      endocannabinoid systems in those processes leading to the comorbidity of
      alcoholism and antisocial behaviour.

PMID- 17449445
TI  - Animal models and treatments for addiction and depression co-morbidity.
AB  - The high rates of co-morbidity of drug addiction with depression may be
      attributable to shared neurobiology. Here, we discuss shared neurobiological
      substrates in drug withdrawal and depression, with an emphasis on changes in
      brain reward circuitry that may underlie anhedonia, a core symptom of depression
      and drug withdrawal. We explored experimentally whether clinical antidepressant
      medications or other treatments would reverse the anhedonia observed in rats
      undergoing spontaneous nicotine or amphetamine withdrawal, defined operationally
      as elevated brain reward thresholds. The co-administration of selective serotonin
      reuptake inhibitors with a serotonin-1A receptor antagonist, or the tricyclic
      antidepressant desipramine, or the atypical antidepressant bupropion ameliorated
      nicotine or amphetamine withdrawal in rats. Thus, increases in monoaminergic
      neurotransmission, or neuroadaptations induced by increased monoaminergic
      neurotransmission, ameliorated depression-like aspects of drug withdrawal.
      Further, chronic pretreatment with the atypical antipsychotic clozapine, that has
      some efficacy in the treatment of the depression-like symptoms of schizophrenia,
      attenuated nicotine and amphetamine withdrawal. Finally, a metabotropic glutamate
      2/3 receptor antagonist reversed threshold elevations associated with nicotine
      withdrawal. The effects of these pharmacological manipulations are consistent
      with the altered neurobiology observed in drug withdrawal and depression. Thus,
      these data support the hypothesis of common substrates mediating the depressive
      symptoms of drug withdrawal and those seen in psychiatric patients. Accordingly,
      the anhedonic state associated with drug withdrawal can be used to study the
      neurobiology of anhedonia, and thus contribute to the identification of novel
      targets for the treatment of depression-like symptoms seen in various psychiatric
      and neurological disorders.

PMID- 17449450
TI  - Are some genetic risk factors common to schizophrenia, bipolar disorder and
      depression? Evidence from DISC1, GRIK4 and NRG1.
AB  - Depression is common in patients with schizophrenia and it is well established
      from family studies that rates of depression are increased among relatives of
      probands with schizophrenia, making it likely that the phenotypes described under
      the categories of affective and non-affective psychoses share some genetic risk
      factors. Family linkage studies have identified several chromosomal regions
      likely to contain risk genes for schizophrenia and bipolar disorder, suggesting
      common susceptibility loci. Candidate gene association studies have provided
      further evidence to suggest that some genes including two of the most studied
      candidates, Disrupted in Schizophrenia 1 (DISC1) and Neuregulin 1 (NRG1) may be
      involved in both types of psychosis. We have recently identified another strong
      candidate for a role in both schizophrenia and affective disorders, GRIK4 a
      glutamate receptor mapped to chromosome 11q23 [Glutamate Receptor, Ionotropic,
      Kainate, type 4]. This gene is disrupted by a translocation breakpoint in a
      patient with schizophrenia, and case control studies show significant association
      of GRIK4 with both schizophrenia and bipolar disorder. Identifying genes
      implicated in the psychoses may eventually provide the basis for classification
      based on biology rather than symptoms, and suggest novel treatment strategies for
      these complex brain disorders.

PMID- 17449451
TI  - Early effects of neuropathy-inducing organophosphates on in vivo concentrations
      of three neurotrophins.
AB  - Exposure to OP compounds that inhibit neurotoxic esterase (NTE) induces a delayed
      neuropathy (OPIDN) characterized by Wallerian-like degeneration of long axons in
      certain animals, including humans. Pope et al. (Toxicol. Lett. 75:111-117, 1995)
      found that neurite outgrowth occurred following the addition of spinal cord
      extracts from chickens with active OPIDN to neuroblastoma cells, suggesting
      growth factor expression during the neuropathy. We hypothesized that, shortly
      after exposure to a neuropathic OP compound, the central nervous system (CNS)
      attempts to recover from the toxic insult through upregulation of the
      neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor
      (BDNF), and neurotrophin-3 (NT-3) in susceptible regions of the nervous system.
      We hypothesized that such upregulation is transient and cannot be sustained. To
      test this hypothesis, we exposed 10-week-old chickens to a neuropathic OP
      compound (PSP, 2.5 mg/kg), a non-neuropathic OP compound (paraoxon, 0.10 mg/kg),
      and vehicle (DMSO, 0.5 ml/kg) intramuscularly. By day 8, all PSP-treated birds
      demonstrated clinical signs of OPIDN. We sacrificed chickens by pentobarbital
      overdose at 4, 8, 24, and 48 hours, and 5 and 10 days post-exposure and confirmed
      NTE inhibition in birds treated with PSP 4 and 24 hours earlier. Enzyme-linked
      immunosorbant assays indicated that NGF, BDNF, and NT-3 are found in chicken
      lumbar spinal cord after exposure to a neuropathic OP compound. However, exposure
      to the neuropathic OP compound, PSP, did not preferentially elevate levels of
      NGF, BDNF, and NTE compared to the non-neuropathic OP compound, paraoxon. This
      suggests that these neurotrophins alone do not contribute to a sustained
      regenerative effort in the CNS.

PMID- 17449452
TI  - Melatonin decreases the oxidative stress produced by 2,4-dichlorophenoxyacetic
      acid in rat cerebellar granule cells.
AB  - 2,4-Dichlorophenoxyacetic acid (2,4-D) is one of the most widely used herbicides
      due to its relatively moderate toxicity and to its biodegradability in the soil.
      In toxic concentrations, 2,4-D displays strong neurotoxicity, partly due to
      generation of free radicals. Since melatonin has remarkable antioxidant
      properties, the objective of this study was to assess to what extent it was
      effective in preventing the 2,4-D effect on redox balance of rat cerebellar
      granule cells (CGC) in vitro. Cellular viability, generation of reactive oxygen
      species (ROS) and reactive nitrogen species (RNS), reduced glutathione (GSH)
      levels, and the activities of the antioxidant enzymes Cu/Zn-superoxide dismutase
      (Cu/Zn-SOD), Mn-SOD, selenium-glutathione peroxidase (Se-GPx) and catalase (CAT)
      were measured in CGC exposed to 2,4-D and/or melatonin for 48 h. In CGC cultures
      exposed to 2,4-D, cell viability, GSH levels and CAT activity decreased
      significantly whereas ROS generation and Se-GPx activities were augmented. Except
      for Se-GPx activity, all these changes were counteracted by the concomitant
      addition of 0.1 or 0.5 mM melatonin. In addition, incubation of CGC with
      melatonin alone resulted in augmentation of cell viability, GSH levels and Se-GPx
      activity. RNS generation and SOD activity remained unaffected by either
      treatment. Since melatonin was able to counteract most of redox changes produced
      by 2,4-D in CGC in culture, the experimental evidence reported further support
      the efficacy of melatonin to act as a neuroprotector.

PMID- 17449453
TI  - In vitro reactivation potency of acetylcholinesterase reactivators--K074 and K075
      -to reactivate tabun-inhibited human brain cholinesterases.
AB  - In this work, two oximes for the treatment of tabun-inhibited
      acetylcholinesterase (AChE; EC 3.1.1.7), K074 (1,4-bis(4
      hydroxyiminomethylpyridinium)butane dibromide) and K075 ((E)-1,4-bis(4
      hydroxyiminomethylpyridinium)but-2-en dibromide), were tested in vitro as
      reactivators of AChE. Comparison was made with currently used AChE reactivators
      (pralidoxime, HI-6, methoxime and obidoxime). Human brain homogenate was taken as
      an appropriate source of the cholinesterases. As resulted, oxime K074 appears to
      be the most potent reactivator of tabun-inhibited AChE, with reactivation potency
      comparable to that of obidoxime. A second AChE reactivator, K075, does not attain
      as great a reactivation potency as K074, although its maximal reactivation (17%)
      was achieved at relevant concentrations for humans.

PMID- 17449454
TI  - Neonatal dopamine depletion induces changes in morphogenesis and gene expression
      in the developing cortex.
AB  - The mesocorticolimbic dopamine (DA) system is implicated in mental health
      disorders affecting attention, impulse inhibition and other cognitive functions.
      It has also been involved in the regulation of cortical morphogenesis. The
      present study uses focal injections of 6-hydroxydopamine (6-OHDA) into the medial
      forebrain bundle of BALB/c mice to examine morphological, behavioral and
      transcriptional responses to selective DA deficit in the fronto-parietal cortex.
      Mice that received injections of 6-OHDA on postnatal day 1 (PND1) showed
      reduction in DA levels in their cortices at PND7. Histological analysis at PND120
      revealed increased fronto-cortical width, but decreased width of somatosensory
      parietal cortex. Open field object recognition suggested impaired response
      inhibition in adult mice after 6-OHDA treatment. Transcriptional analyses using
      17K mouse microarrays showed that such lesions caused up-regulation of 100 genes
      in the cortex at PND7. Notably, among these genes are Sema3A which plays a
      repulsive role in axonal guidance, RhoD which inhibits dendritic growth and
      tubulin beta-5 microtubule subunit. In contrast, 127 genes were down-regulated,
      including CCT-epsilon and CCT-zeta that play roles in actin and tubulin folding.
      Thus, neonatal DA depletion affects transcripts involved in control of
      cytoskeletal formation and pathway finding, instrumental for normal
      differentiation and synaptogenesis. The observed gene expression changes are
      consistent with histological cortical and behavioral impairments in the adult
      mice treated with 6-OHDA on PND1. Our results point towards specific molecular
      targets that might be involved in disease process mediated by altered
      developmental DA regulation.

PMID- 17449455
TI  - Amphetamine and mCPP effects on dopamine and serotonin striatal in vivo
      microdialysates in an animal model of hyperactivity.
AB  - In the neonatally 6-hydroxydopamine (6-OHDA)-lesioned rat hyperlocomotor
      activity, first described in the 1970s, was subsequently found to be increased by
      an additional lesion with 5,7-dihydroxytryptamine (5,7-DHT) (i.c.v.) in
      adulthood. The latter animal model (i.e., 134 microg 6-OHDA at 3 d postbirth plus
      71 microg 5,7-DHT at 10 weeks; desipramine pretreatments) was used in this study,
      in an attempt to attribute hyperlocomotor attenuation by D,L-amphetamine sulfate
      (AMPH) and m-chlorophenylpiperazine di HCl (mCPP), to specific changes in
      extraneuronal (i.e., in vivo microdialysate) levels of dopamine (DA) and/or
      serotonin (5-HT). Despite the 98-99% reduction in striatal tissue content of DA,
      the baseline striatal microdialysate level of DA was reduced by 50% or less at 14
      weeks, versus the intact control group. When challenged with AMPH (0.5 mg/kg),
      the microdialysate level of DA went either unchanged or was slightly reduced over
      the next 180 min (i.e., 20 min sampling), while in the vehicle group and 5,7-DHT
      (alone) lesioned group, the microdialysate level was maximally elevated by
      approximately 225% and approximately 450%, respectively--and over a span of
      nearly 2 h. Acute challenge with mCPP (1 mg/kg salt form) had little effect on
      microdialysate levels of DA, DOPAC and 5-HT. Moreover, there was no consistent
      change in the microdialysate levels of DA, DOPAC, and 5-HT between intact, 5-HT
      lesioned rats, and DA-lesioned rats which might reasonably account for an
      attenuation of hyperlocomotor activity. These findings indicate that there are
      other important neurochemical changes produced by AMPH- and mCPP-attenuated
      hyperlocomotor activity, or perhaps a different brain region or multiple brain
      regional effects are involved in AMPH and mCPP behavioral actions.

PMID- 17449456
TI  - The 'current state of play' in transplantation and restoration research of the
      CNS.
AB  - At the Network of European CNS Transplantation and Restoration 2005 meeting, a
      number of revealing studies were reported that could be divided into two broad,
      overlapping groups; methods to maximize the efficacy of cell transplants in vitro
      and their use in vivo. A variety of different forms of stem cells ranging from
      embryonic stem cells to cells expressing specific genes following lentiviral
      vector transduction were investigated. Methods to improve the efficacy of
      transplants included the cotransplantation of other cell lines, exposure of the
      recipient to an enriched environment and methods to promote differentiation. The
      majority of the studies, if disease-specific, related to Parkinson's disease, but
      additional reports on Huntington's disease, Alzheimer's disease and spinal cord
      injury were also present. A few studies related to different animal models of
      disease. Overall the future for transplantation and restoration of functional
      activity in diseased states is very promising.

PMID- 17449457
TI  - The 6-hydroxydopamine model of Parkinson's disease.
AB  - The neurotoxin 6-hydroxydopamine (6-OHDA) continues to constitute a valuable
      topical tool used chiefly in modeling Parkinson's disease in the rat. The
      classical method of intracerebral infusion of 6-OHDA involving a massive
      destruction of nigrostriatal dopaminergic neurons, is largely used to investigate
      motor and biochemical dysfunctions in Parkinson's disease. Subsequently, more
      subtle models of partial dopaminergic degeneration have been developed with the
      aim of revealing finer motor deficits. The present review will examine the main
      features of 6-OHDA models, namely the mechanisms of neurotoxin-induced
      neurodegeneration as well as several behavioural deficits and motor dysfunctions,
      including the priming model, modeled by this means. An overview of the most
      recent morphological and biochemical findings obtained with the 6-OHDA model will
      also be provided, particular attention being focused on the newly investigated
      intracellular mechanisms at the striatal level (e.g., A(2A) and NMDA receptors,
      PKA, CaMKII, ERK kinases, as well as immediate early genes, GAD67 and peptides).
      Thanks to studies performed in the 6-OHDA model, all these mechanisms have now
      been hypothesised to represent the site of pathological dysfunction at cellular
      level in Parkinson's disease.

PMID- 17449458
TI  - Exploring neurocircuitries of the basal ganglia by intracerebral administration
      of selective neurotoxins.
AB  - The detailed anatomy of the monoamine pathways of the rat, first described by the
      students of Nils Ake Hillarp in Sweden, provided the basis for a neurocircuitry
      targeted pharmacology, leading to important therapeutic breakthroughs. Progress
      was achieved by the introduction of accurate lesion techniques based on selective
      neurotoxins. Systematic intracerebral injections of 6-hydroxydopamine let Urban
      Ungerstedt at the Karolinska Institutet, Stockholm, Sweden, to propose the first
      stereotaxic mapping of the monoamine pathways in the rat brain; and the
      'Rotational Behaviour', as a classical model for screening drugs useful for
      alleviating Parkinson's disease and other neuropathologies. The direction of the
      rotational behaviour induced by drugs administrated to unilaterally 6
      hydroxydopamine-lesioned rats reveals their mechanism of action at dopamine
      synapses, as demonstrated when rotational behaviour was combined with
      microdialysis. The model was useful for proposing a role for dopamine receptors
      in the gating of the flow of information integrated and/or modulated by the basal
      ganglia, through different efferent pathways; notably the striatopallidal system,
      via D(2) receptors, and the striatonigral system, via D(1) receptors. The role of
      other dopamine receptor subtypes on rotational behaviour has not yet been
      clarified.

PMID- 17449459
TI  - Neurotoxicity of substituted amphetamines: molecular and cellular mechanisms.
AB  - The amphetamines, including amphetamine (AMPH), methamphetamine (METH) and 3,4
      methylenedioxymethamphetamine (MDMA), are among abused drugs in the US and
      throughout the world. Their abuse is associated with severe neurologic and
      psychiatric adverse events including the development of psychotic states. These
      neuropsychiatric complications might, in part, be related to drug-induced
      neurotoxic effects, which include damage to dopaminergic and serotonergic
      terminals, neuronal apoptosis, as well as activated astroglial and microglial
      cells in the brain. The purpose of the present review is to summarize the toxic
      effects of AMPH, METH and MDMA. The paper also presents some of the factors that
      are thought to underlie this toxicity. These include oxidative stress,
      hyperthermia, excitotoxicity and various apoptotic pathways. Better understanding
      of the cellular and molecular mechanisms involved in their toxicity should help
      to generate modern therapeutic approaches to prevent or attenuate the long-term
      consequences of amphetamine use disorders in humans.

PMID- 17449460
TI  - Glutamate antagonists are neurotoxins for the developing brain.
AB  - Neurotransmitters and neuromodulators are essential for normal nervous system
      development. Disturbances in the expression timetable or intensity of
      neurotransmitter signalling during critical periods of brain development can lead
      to permanent damage. Neuroactive drugs and environmental toxins interfere with
      neurotransmitter signalling and may thereby provide one mechanism underlying
      neurological abnormalities. Glutamate is the main excitatory neurotransmitter in
      the mammalian central nervous system and mediates neurotransmission across most
      excitatory synapses. In this article we review the timely expression of the
      excitatory neurotransmitter glutamate and its receptors during brain development,
      briefly review glutamate receptor antagonists and present clinical and
      experimental evidence describing their adverse effects in the developing brain.

PMID- 17449461
TI  - Model fusion, the next phase in developing animal models for Parkinson's disease.
AB  - Within the past 25 years, discoveries of environmental and monogenetic forms of
      parkinsonism have shaped the direction of Parkinson's disease (PD) research and
      development of experimental systems to study PD. In this review, we outline a
      remarkable array of in vivo models available, with particular emphasis on their
      benefits and pitfalls and the contribution each has made to enhance our
      understanding of pathological mechanisms involved in PD. Further, we discuss the
      increasingly popular approach of "model fusion" to create a new generation of
      animal systems in which to study gene-environment interactions, and the
      usefulness of such models in capturing the most common events underlying PD.

PMID- 17449463
TI  - The blood-brain barrier for catecholamines - revisited.
AB  - Although it is well-recognized that catecholamines are generally unable to
      penetrate the developed blood-brain barrier (BBB) to gain entry into brain,
      except at circumventricular sites where the BBB is absent or deficient,
      ontogenetic development of this barrier seems to have escaped systematic study.
      To explore BBB development, several approaches were used. In the first study rats
      were treated once on a specific day of postnatal ontogeny, as early as the day of
      birth, with the neurotoxin 6-hydroxydopamine (6-OHDA; 60 mg/kg), and then
      terminated in adulthood for regional analysis of endogenous norepinephrine (NE)
      content of brain. In another study, rats were treated once, on a specific day of
      postnatal ontogeny, with the BBB-permeable neurotoxin 6-hydroxydopa (6-OHDOPA; 60
      mg/kg) following pretreatment with the BBB-impermeable amino acid decarboxylase
      inhibitor carbidopa (100 mg/kg IP), then terminated in adulthood for regional
      analysis of endogenous NE content of brain. In the third study rats were treated
      once, on a specific day of postnatal ontogeny, with the analog [3H]metaraminol,
      and terminated 1 hour later for determination of regional distribution of tritium
      in brain. On the basis of [3H]metaraminol distribution and NE depletions after
      neurotoxin treatments, it is evident that the BBB in neocortex, striatum,
      cerebellum and other brain regions forms in stages over a period of at least 2
      weeks from birth. Moreover, because the BBB consists of several element (physical
      , ion-restrictive-, and enzymatic-barrier), the method employed will derive data
      mainly applicable to the targeted aspect of the barrier, which may or may not
      necessarily coincide with elements of the barrier that have a different rate of
      ontogenetic development. Accordingly, it is evident that some aspects of physical
      and ion-restrictive elements of the BBB form within approximately the first week
      after birth in rat neocortex and striatum, while enzymatic elements of the BBB
      form more than than 2 weeks later. Regardless, the BBB forms at earlier times in
      forebrain vs hindbrain regions.

PMID- 17449464
TI  - High resolution footprinting of the hepatitis C virus polymerase NS5B in complex
      with RNA.
AB  - The nucleic acid binding channel of the hepatitis C virus RNA polymerase remains
      to be defined. Here we employed complementary footprinting techniques and show
      that the enzyme binds to a newly synthesized duplex of approximately seven to
      eight base pairs. Comparative analysis of surface topologies of free enzyme
      versus the nucleoprotein complex revealed certain lysines and arginines that are
      protected from chemical modification upon RNA binding. The protection pattern
      helps to define the trajectory of the nucleic acid substrate. Lys(81), Lys(98),
      Lys(100), Lys(106), Arg(158), Arg(386), and Arg(394) probably interact with the
      bound RNA. The selective protection of amino acids of the arginine-rich region in
      helix T points to RNA-induced conformational rearrangements. Together, these
      findings suggest that RNA-protein interaction through the entire substrate
      binding channel can modulate intradomain contacts at the C terminus.

PMID- 17449462
TI  - Neurobehavioural and molecular changes induced by methylmercury exposure during
      development.
AB  - There is an increasing body of evidence on the possible environmental influence
      on neurodevelopmental and neurodegenerative disorders. Both experimental and
      epidemiological studies have demonstrated the distinctive susceptibility of the
      developing brain to environmental factors such as lead, mercury and
      polychlorinated biphenyls at levels of exposure that have no detectable effects
      in adults. Methylmercury (MeHg) has long been known to affect neurodevelopment in
      both humans and experimental animals. Neurobehavioural effects reported include
      altered motoric function and memory and learning disabilities. In addition, there
      is evidence from recent experimental neurodevelopmental studies that MeHg can
      induce depression-like behaviour. Several mechanisms have been suggested from in
      vivo- and in vitro-studies, such as effects on neurotransmitter systems,
      induction of oxidative stress and disruption of microtubules and intracellular
      calcium homeostasis. Recent in vitro data show that very low levels of MeHg can
      inhibit neuronal differentiation of neural stem cells. This review summarises
      what is currently known about the neurodevelopmental effects of MeHg and consider
      the strength of different experimental approaches to study the effects of
      environmentally relevant exposure in vivo and in vitro.

PMID- 17449465
TI  - Factor structure and clinical implications of child behavior checklist/1.5-5
      ratings in a sample of girls adopted from China.
AB  - OBJECTIVE: This study assessed psychometric properties of the Child Behavior
      Checklist (CBCL/1.5-5) and explored clinical insights from its use in a sample of
      adopted Chinese girls. METHODS: Parental ratings were obtained on 707 adopted
      Chinese girls, ages 1.50-5.92 years (M = 3.24, SD = 1.26). Confirmatory factor
      analysis (CFA), employing robust weighted least squares estimation, was used to
      evaluate the instrument's seven-factor correlated structure. Profiles of scores
      were analyzed descriptively for clinical insights. RESULTS: The CFAs indicated
      that the fit of Achenbach and Rescorla's (2000 Manual for the ASEBA preschool
      forms & profiles. Burlington, VT: University of Vermont, Research Centre for
      Children, Youth, & Families) model to the data obtained from the adopted Chinese
      girls was acceptable using either a 2-point response scale or the original 3
      point response scale for the 67 items from which the seven syndromes or
      correlated factors are derived. Values for the root mean square error of
      approximation (RMSEA) for the 2-point and 3-point response scales were .049 and
      .053, respectively. The RMSEA of .049 for the model using the dichotomously
      scored items was slightly better than what Achenbach and Rescorla (2000) reported
      for the same model (.06). CONCLUSIONS: The study provides additional evidence of
      the factorial validity of the CBCL/1.5-5 and supports its use with Chinese girls
      adopted into North American families. While the Chinese girls showed similar or
      better behavioral adjustment, compared to a reference group from the CBCL's
      normative sample, they tended to manifest higher levels of sleep problems.

PMID- 17449466
TI  - Effects of modifying physical activity and sedentary behavior on psychosocial
      adjustment in overweight/obese children.
AB  - OBJECTIVES: To evaluate the relationship between changes in physical activity
      (PA), sedentary behavior, and physical self-perceptions and global self-worth in
      30, 8-12 years old, overweight/obese children (13 boys, 17 girls). METHODS:
      Secondary analyses from a randomized controlled trial designed to increase PA and
      reduce sedentary behavior. PA was measured by accelerometers worn by participants
      every day for 8 weeks. Sedentary behavior, defined as minutes per day spent in
      television viewing, was assessed by self-report. RESULTS: Increases in PA were
      associated with increases in perceived physical conditioning (r = .54, p < .01),
      body satisfaction (r = .55, p < .01), and overall physical self-worth (r = .44, p
      < .05) independent of changes in body mass index (BMI). Reductions in TV viewing
      were also related to increased physical and global self-worth. CONCLUSIONS:
      Increases in PA are associated with improvements in physical self-perceptions but
      not global self-worth, while reductions in TV viewing are associated with
      increased physical and global self-worth, and these psychosocial benefits appear
      to be independent of changes in adiposity.

PMID- 17449467
TI  - Structural and functional characterization of a novel T cell receptor co
      regulatory protein complex, CD97-CD55.
AB  - CD97, the archetypal member of the EGF-TM7 protein family, is constitutively
      expressed on granulocytes and monocytes and rapidly up-regulated on T and B cells
      following activation. The key isoform of CD97 expressed on leukocytes binds the
      complement regulatory protein CD55 (also termed decay-accelerating factor). CD97
      has been shown recently to mediate co-stimulation of T cells via CD55. Here, we
      demonstrate that blocking the interaction between CD55 on monocytes and CD97 on T
      cells leads to inhibition of proliferation and interferon-gamma secretion. This
      implies that bidirectional interactions between CD97 and CD55 are involved in T
      cell regulation. Structural studies presented here reveal the molecular basis for
      this activity. We have solved the structure of EMR2, a very close homolog of
      CD97, using x-ray crystallography. NMR-based chemical shift mapping of the EMR2
      CD55 interaction has allowed us to generate a model for the CD97-CD55 complex.
      The structure of the complex reveals that the T cell and complement regulatory
      activities of CD55 occur on opposite faces of the molecule. This suggests that
      CD55 might simultaneously regulate both the innate and adaptive immune responses,
      and we have shown that CD55 can still regulate complement when bound to CD97.

PMID- 17449468
TI  - RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF
      kappaB activation by targeting TAB2/3 for degradation.
AB  - Inflammation is a homeostatic mechanism that limits the effects of infectious
      agents. Tumor necrosis factor (TNF) and interleukin (IL)-1 are two cytokines that
      induce inflammation through activation of the transcription factor NF-kappaB.
      Various studies have suggested that two homologous and structurally related
      adapter proteins TAB2 and TAB3 play redundant roles in TNF- and IL-1-mediated NF
      kappaB activation pathways. Both TAB2 and TAB3 contain CUE, coiled-coil, and
      nuclear protein localization 4 zinc finger (NZF) domains. The NZF domains of
      TAB2/3 are critical for TAB2/3 to bind to Lys(63)-linked polyubiquitin chains of
      other adaptor proteins, such as receptor-interacting protein and TRAF6, which are
      two signaling proteins essential for TNF- and IL-1-induced NF-kappaB activation,
      respectively. In a search for proteins containing NZF domains conserved with
      those of TAB2/3, we identified RBCK1, which has been shown to act as an E3
      ubiquitin ligase in iron metabolism. Overexpression of RBCK1 negatively regulates
      TAB2/3-mediated and TNF- and IL-1-induced NF-kappaB activation, whereas knockdown
      of RBCK1 by RNA interference potentiates TNF- and IL-1-induced NF-kappaB
      activation. RBCK1 physically interacts with TAB2/3 and facilitates degradation of
      TAB2/3 through a proteasome-dependent process. Taken together, our findings
      suggest that RBCK1 is involved in negative regulation of inflammatory signaling
      triggered by TNF and IL-1 through targeting TAB2/3 for degradation.

PMID- 17449469
TI  - Molecular characterization of the Tax-containing HTLV-1 enhancer complex reveals
      a prominent role for CREB phosphorylation in Tax transactivation.
AB  - Transcriptional activation of human T-cell leukemia virus type 1 (HTLV-1) is
      mediated by the viral oncoprotein Tax, which utilizes cellular transcriptional
      machinery to perform this function. The viral promoter carries three cyclic AMP
      response elements (CREs), which are recognized by the cellular transcription
      factor cAMP-response element-binding protein (CREB). Tax binds to GC-rich
      sequences that immediately flank the CREs. The coactivator CREB-binding protein
      (CBP)/p300 binds to this promoter-bound ternary complex, which promotes the
      initiation of HTLV-1 transcription. Protein kinase A phosphorylation of CREB at
      serine 133 facilitates transcription from cellular CREs by recruiting CBP/p300
      via its KIX domain. However, it remains controversial whether CREB
      phosphorylation plays a role in Tax transactivation. In this study, we
      biochemically characterized the quaternary complex formed by Tax, CREB, KIX, and
      the viral CRE by examining the individual molecular interactions that contribute
      to Tax stabilization in the complex. Our data show KIX, Ser(133)-phosphorylated
      CREB, and vCRE DNA are all required for stable Tax incorporation into the complex
      in vitro. Consonant with a fundamental role for CREB phosphorylation in Tax
      recruitment to the complex, we found that CREB is highly phosphorylated in a
      panel of HTLV-1-infected human T-cell lines. Significantly, we show that Tax is
      directly responsible for promoting elevated levels of CREB phosphorylation.
      Together, these data support a model in which Tax promotes CREB phosphorylation
      in vivo to ensure availability for Tax transactivation. Because pCREB has been
      implicated in leukemogenesis, enhancement of CREB phosphorylation by the virus
      may play a role in the etiology of adult T-cell leukemia.

PMID- 17449470
TI  - DNA polymerases eta and theta function in the same genetic pathway to generate
      mutations at A/T during somatic hypermutation of Ig genes.
AB  - Somatic hypermutation of the Ig genes requires the activity of multiple DNA
      polymerases to ultimately introduce mutations at both A/T and C/G base pairs.
      Mice deficient for DNA polymerase eta (POLH) exhibited an approximately 80%
      reduction of the mutations at A/T, whereas absence of polymerase (POLQ) resulted
      in approximately 20% reduction of both A/T and C/G mutations. To investigate
      whether the residual A/T mutations observed in the absence of POLH are generated
      by POLQ and how these two polymerases might cooperate or compete with each other
      to generate A/T mutations, here we have established mice deficient for both POLH
      and POLQ. Polq(-/-)Polh(-/-) mice, however, did not show a further decrease of
      A/T mutations as compared with Polh(-/-) mice, suggesting that POLH and POLQ
      function in the same genetic pathway in the generation of these mutations.
      Frequent misincorporation of nucleotides, in particular opposite template T, is a
      known feature of POLH, but the efficiency of extension beyond the
      misincorporation differs significantly depending on the nature of the mispairing.
      Remarkably, we found that POLQ catalyzed extension more efficiently than POLH
      from all types of mispaired termini opposite A or T. Moreover, POLQ was able to
      extend mispaired termini generated by POLH albeit at a relatively low efficiency.
      These results reveal genetic and biochemical interactions between POLH and POLQ
      and suggest that POLQ might cooperate with POLH to generate some of the A/T
      mutations during the somatic hypermutation of Ig genes.

PMID- 17449471
TI  - Specific Grb2-mediated interactions regulate clathrin-dependent endocytosis of
      the cMet-tyrosine kinase.
AB  - Lysosomal degradation of the receptor-tyrosine kinase cMet requires receptor
      ubiquitination by the E3 ubiquitin ligase Cbl followed by clathrin-dependent
      internalization. A role for Cbl as an adaptor for cMet internalization has been
      previously reported. However, the requirement for Cbl ubiquitin ligase activity
      in this process and its mode of recruitment to cMet has yet to be determined. Cbl
      can directly bind cMet at phosphotyrosine 1003 or indirectly via Grb2 to
      phosphotyrosine 1356 in the multisubstrate binding domain of cMet. The direct
      binding of Cbl with cMet is critical for receptor degradation and not receptor
      internalization. Here we show a strict requirement for Grb2 and the ubiquitin
      ligase activity of Cbl for cMet endocytosis. Receptor internalization was
      impaired by small interfering RNA depletion of Grb2, overexpression of dominant
      negative Grb2 mutants, and point mutations in the cMet multisubstrate docking
      site that inhibits the direct association of Grb2 with cMet. The requirement for
      Grb2 was specific and did not involve the multiadaptor Gab1. cMet internalization
      was impaired in cells expressing an ubiquitin ligase-deficient Cbl mutant or
      conjugation-deficient ubiquitin but was unaffected in cells expressing a Cbl
      mutant that is unable to bind cMet directly. Expression of a Cbl-Grb2 chimera
      rescued impaired cMet endocytosis in cells depleted of endogenous Grb2. These
      results indicate that the ubiquitin ligase activity of Cbl is critical for
      clathrin-dependent cMet internalization and suggest a role for Grb2 as an
      intermediary linking Cbl ubiquitin ligase activity to this process.

PMID- 17449472
TI  - Liver fatty acid-binding protein initiates budding of pre-chylomicron transport
      vesicles from intestinal endoplasmic reticulum.
AB  - The rate-limiting step in the transit of absorbed dietary fat across the
      enterocyte is the generation of the pre-chylomicron transport vesicle (PCTV) from
      the endoplasmic reticulum (ER). This vesicle does not require coatomer-II (COPII)
      proteins for budding from the ER membrane and contains vesicle-associated
      membrane protein 7, found in intestinal ER, which is a unique intracellular
      location for this SNARE protein. We wished to identify the protein(s) responsible
      for budding this vesicle from ER membranes in the absence of the requirement for
      COPII proteins. We chromatographed rat intestinal cytosol on Sephacryl S-100 and
      found that PCTV budding activity appeared in the low molecular weight fractions.
      Additional chromatographic steps produced a single major and several minor bands
      on SDS-PAGE. By tandem mass spectroscopy, the bands contained both liver and
      intestinal fatty acid-binding proteins (L- and I-FABP) as well as four other
      proteins. Recombinant proteins for each of the six proteins identified were
      tested for PCTV budding activity; only L-FABP and I-FABP (23% the activity of L
      FABP) were active. The vesicles generated by L-FABP were sealed, contained
      apolipoproteins B48 and AIV, were of the same size as PCTV on Sepharose CL-6B,
      and by electron microscopy, excluded calnexin and calreticulin but did not fuse
      with cis-Golgi nor did L-FABP generate COPII-dependent vesicles. Gene-disrupted L
      FABP mouse cytosol had 60% the activity of wild type mouse cytosol. We conclude
      that L-FABP can select cargo for and bud PCTV from intestinal ER membranes.

PMID- 17449473
TI  - The nuclear export signal of splicing factor Uap56p interacts with nuclear pore
      associated protein Rae1p for mRNA export in Schizosaccharomyces pombe.
AB  - Mammalian UAP56 or its homolog Sub2p in Saccharomyces cerevisiae are members of
      the ATP-dependent RNA helicase family and are required for splicing and nuclear
      export of mRNA. Previously we showed that in Schizosaccharomyces pombe Uap56p is
      critical for mRNA export. It links the mRNA adapter Mlo3p, a homolog of Yra1p in
      S. cerevisiae or Aly in mammals, to nuclear pore-associated mRNA export factor
      Rae1p. In this study we show that, in contrast to S. cerevisiae, Uap56p in S.
      pombe is not required for pre-mRNA splicing. The putative RNA helicase function
      of Uap56p is not required for mRNA export. However, the RNA-binding motif of
      Uap56p is critical for nuclear export of mRNA. Within Uap56p we identified
      nuclear import and export signals that may allow it to shuttle between the
      nucleus and the cytoplasm. We found that Uap56p interacts with Rae1p directly via
      its nuclear export signal, and this interaction is critical for the nuclear
      export activity of Uap56p as well as for exporting mRNA. RNA binding and the
      ability to shuttle between the nucleus and cytoplasm are important features of
      mRNA export carriers such as HIV-Rev. Our results suggest that Uap56p could
      function similarly as an export carrier of mRNA in S. pombe.

PMID- 17449474
TI  - Group G streptococcal IgG binding molecules FOG and protein G have different
      impacts on opsonization by C1q.
AB  - Recent epidemiological data on diseases caused by beta-hemolytic streptococci
      belonging to Lancefield group C and G (GCS, GGS) underline that they are an
      emerging threat to human health. Among various virulence factors expressed by GCS
      and GGS isolates from human infections, M and M-like proteins are considered
      important because of their anti-phagocytic activity. In addition, protein G has
      been implicated in the accumulation of IgG on the bacterial surface through non
      immune binding. The function of this interaction, however, is still unknown.
      Using isogenic mutants lacking protein G or the M-like protein FOG (group G
      streptococci), respectively, we could show that FOG contributes substantially to
      IgG binding. A detailed characterization of the interaction between IgG and FOG
      revealed its ability to bind the Fc region of human IgG and its binding to the
      subclasses IgG1, IgG2, and IgG4. FOG was also found to bind IgG of several animal
      species. Surface plasmon resonance measurements indicate a high affinity to human
      IgG with a dissociation constant of 2.4 pm. The binding site was localized in a
      central motif of FOG. It has long been speculated about anti-opsonic functions of
      streptococcal Fc-binding proteins. The presented data for the first time provide
      evidence and, furthermore, indicate functional differences between protein G and
      FOG. By obstructing the interaction between IgG and C1q, protein G prevented
      recognition by the classical pathway of the complement system. In contrast, IgG
      that was bound to FOG remained capable of binding C1q, an effect that may have
      important consequences in the pathogenesis of GGS infections.

PMID- 17449475
TI  - Three hydroxyproline-rich glycopeptides derived from a single petunia polyprotein
      precursor activate defensin I, a pathogen defense response gene.
AB  - Hydroxyproline-rich glycopeptides (HypSys peptides) are recently discovered 16-20
      amino acid defense signals in tobacco and tomato leaves that are derived from
      cell wall-associated precursors. The peptides are powerful wound signals that
      activate the expression of defensive genes in tobacco and tomato leaves in
      response to herbivore attacks. We have isolated a cDNA from petunia (Petunia
      hybrida) leaves encoding a putative protein of 214 amino acids that is a homolog
      of tobacco and tomato HypSys peptide precursors and is inducible by wounding and
      MeJA. The deduced protein contains a leader sequence and four predicted proline
      rich peptides of 18-21 amino acids. Three of the four peptides were isolated from
      leaves, and each peptide contained hydroxylated prolines and glycosyl residues.
      Each of the peptides has a -GR- motif at its N terminus, indicating that it may
      be the substrate site for a processing enzyme. The peptides were active in a
      petunia suspension culture bioassay at nanomolar concentrations, but they did not
      induce the expression of defense genes that are directed against herbivores, as
      found in tobacco and tomato leaves. They did, however, activate expression of
      defensin 1, a gene associated with inducible defense responses against pathogens.

PMID- 17449476
TI  - Eis (enhanced intracellular survival) protein of Mycobacterium tuberculosis
      disturbs the cross regulation of T-cells.
AB  - The pathogenesis of tuberculosis is complex and its manifestations diverse,
      reflecting a lifetime of dynamic interactions between mycobacterial virulence
      factors and the human immune system. The pathogenic mycobacteria have developed
      strategies to circumvent the major killing mechanisms employed by macrophages and
      take advantage of the enclosed environment within its host cell to avoid humoral
      and cell-mediated immune responses. Secretory proteins play a major role in host
      pathogen interactions. The eis (Rv2416c) gene has been identified as a secretory
      protein, and it has been shown that it enhances intracellular survival of
      Mycobacterium semgmatis in the macrophage cell line. The main aim of this study
      was to gain insight into the biological role of Eis in the host. Stimulation of T
      cells with Eis recombinant protein of Mycobacterium tuberculosis inhibits Con A
      mediated T-cell proliferation in vitro. Treatment of T-cells with Eis inhibits
      ERK1/2, JAK pathway, and subsequent production of tumor necrosis factor-alpha and
      interleukin-4. On the contrary, there is increased production of interferon-gamma
      and interleukin-10, which indicates that immunity in response to Eis treatment is
      skewed away from a protective T(H)1 response and Eis disturbs the cross
      regulation of T-cells.

PMID- 17449477
TI  - Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on
      antibody titre.
AB  - NMO-IgG is a disease-specific autoantibody for neuromyelitis optica (NMO) and its
      target antigen is aquaporin-4 (AQP4) water channel. Recently, we established a
      sensitive anti-AQP4 antibody assay using human AQP4-transfected cells, which
      appeared more sensitive than the original NMO-IgG assay. So far, there has been
      no large-scale study on anti-AQP4 antibody titre in NMO and related disorders. We
      tested 148 sera of patients with NMO, high-risk syndrome of NMO, multiple
      sclerosis (MS), clinically isolated syndrome suggestive of MS and miscellaneous
      diseases. We analysed the relation of anti-AQP4 antibody titres and clinical and
      laboratory parameters. The sensitivity of anti-AQP4 antibody assay was 91% (95%
      CI 79-100) for NMO and 85% (65-100) for high-risk syndrome, and the specificity
      was 100% (91-100) for NMO and high-risk syndrome, that is, none with the other
      disorders was positive. Among 21 anti-AQP4 antibody-positive cases whose NMO-IgG
      were tested, 15 were NMO-IgG-positive and 6 were NMO-IgG-negative. Higher anti
      AQP4 antibody titres were associated with complete blindness and extensive or
      large cerebral lesions on MRI. The lengths of spinal cord lesions on MRI were
      positively correlated with the titres of anti-AQP4 antibody at the nadir of
      exacerbations. A few patients who had short (approx. one to two vertebral
      segments) spinal cord lesions on MRI were also seropositive with low anti-AQP4
      antibody titres, but did have other clinical and MRI features of NMO. Anti-AQP4
      antibody titres became lower after high-dose methylprednisolone, and a follow-up
      showed anti-AQP4 antibody titres remained low in relapse-free periods under
      immunosuppression. Cerebrospinal fluid (CSF)-anti-AQP4 antibody was detected when
      the serum-antibody titres exceeded 512x, at the ratio of 1 (CSF) to 500 (serum).
      Using a sensitive assay, the results of the present study suggest that NMO and
      high-risk syndrome may be essentially anti-AQP4 antibody-associated disorders,
      and that the anti-AQP4 antibody titres have significant clinical and
      immunological implications in NMO.

PMID- 17449478
TI  - Multicentric French study on adult intracranial ependymomas: prognostic factors
      analysis and therapeutic considerations from a cohort of 152 patients.
AB  - Ependymomas account for 2% of all intracranial tumours in adults. Considerable
      controversy continues to exist with regard to their prognostic factors and
      therapeutic management due to the rarity and the heterogeneity of series reported
      so far. The authors report a retrospective study of a homogenous population of
      152 adult patients harbouring intracranial ependymomas from 24 French
      Neurosurgical Centres between 1990 and 2004. All clinico-radiological and follow
      up data were analysed and a central pathologic review was performed by two
      confirmed neuropathologists. The 5- and 10-year overall survival rates were 84.8
      and 76.5%, respectively; the 5- and 10-year progression-free survival rates were
      63.5 and 52.8%, respectively. On multivariate analysis, overall survival rates
      were associated with histological grade (P < 0.001), extent of surgery (P =
      0.006), patient age (P = 0.004) and patient Karnofski performance status (P =
      0.03). The multivariate analysis also revealed that the risk of recurrence was
      associated with high histological grade (P < 0.001), incomplete resection (P <
      0.001) and Karnofski performance status < or = 80 (P = 0.04). The impact of
      radiotherapy was found to be beneficial for incompletely resected low-grade
      ependymomas and to a lesser extent for completely removed high-grade tumours. In
      association with Karnofski performance status and extent of surgery, histological
      grade is a major prognostic factor in adult intracranial ependymomas. The
      application of a simple and reproducible grading scheme using objective
      anaplastic criteria seems useful practically and clinically applicable. The role
      of adjuvant radiotherapy for patients with incompletely resected low-grade
      ependymomas seems to be beneficial but remains to be addressed for high-grade
      tumours.

PMID- 17449479
TI  - Lipid profile, obesity and bone mineral density: the Hertfordshire Cohort Study.
AB  - BACKGROUND: Body mass index (BMI) and bone mineral density (BMD) are positively
      correlated in several studies, but few data relate bone density, lipid profile
      and anthropometric measures. AIM: To investigate these relationships in a large,
      well-characterized cohort of men and women (The Hertfordshire Cohort Study).
      METHODS: Men (n = 465) and women (n = 448) from Hertfordshire, UK were recruited.
      Information was available on demographic and lifestyle factors, anthropometric
      measurements, body fat percentage, fasting triglycerides, cholesterol (total,
      HDL, LDL), apolipoprotein (a) and apolipoprotein (b); bone mineral density (BMD)
      was recorded at the lumbar spine and total femur. RESULTS: BMD at the lumbar
      spine (males r = 0.15, p = 0.001; females r = 0.14, p = 0.003) and total femoral
      region (males r = 0.18, p = 0.0001; females r = 0.16, p = 0.0008) was related to
      serum triglyceride level, even after adjustment for waist-hip ratio, age, social
      class and lifestyle factors, but not if body fat percentage was substituted for
      waist-hip ratio in the regression model. Fasting HDL cholesterol level was
      related to lumbar spine BMD in women (r = -0.15, p = 0.001) and total femoral BMD
      in both sexes (males r = -0.15, p = 0.002; females r = -0.23, p < 0.0001); these
      relationships were also attenuated by adjustment for body fat percentage but not
      waist-hip ratio. No relationships were seen between total or LDL cholesterol with
      BMD. DISCUSSION: In this cohort, relationships between lipid profile and BMD were
      robust to adjustment for one measure of central obesity (waist-hip ratio), but
      not total body fat. This broadly supports the idea that adiposity may confound
      the relationship between lipids and bone mass.

PMID- 17449480
TI  - Socioeconomic disadvantage and primary non-adherence with medication in Sweden.
AB  - OBJECTIVE: Lack of adherence with pharmacological therapy is a public health
      concern that compels tremendous costs for the health care system and the
      community. To analyse the association between socioeconomic disadvantage and
      primary non-adherence with medication, and to explore possible mediating effects
      of trust in health care and lifestyle profile. DESIGN: Cross-sectional population
      based study based on data from the Swedish national public health surveys 2004
      2005. PARTICIPANTS: The study comprised 13603 men and 18292 women aged 21-84
      years who had any contact with a physician at a hospital or primary care centre.
      Measures Primary non-adherence with medication based on whether respondents
      reported that they refrained from purchasing at the pharmacy prescribed
      medication. Socioeconomic Disadvantage Index was based on four different
      indicators of economic deprivation. RESULTS: Socioeconomic disadvantage was
      associated with primary non-adherence with medication independent of long-term
      illness, risky lifestyle, low education, living alone and low trust for health
      care. This association increased with older age, particularly among women. Among
      individuals aged 21-34 years, severe compared with no socioeconomic disadvantage,
      was associated with two-fold increased odds for non-adherence with medication.
      The corresponding odds among individuals aged 65-84 years were three-fold
      increase among elderly men (OR=3.3, 95% CI: 1.4-7.8) and six-fold increase among
      elderly women (OR=6.2, 95% CI: 2.5-15.3). Yet every seventh elderly woman aged 65
      84 years suffered from long-term illness. CONCLUSIONS: Results indicate that
      health policies for 'care on equal terms' in Sweden have been less successful in
      relation to equitable access to prescribed medication, especially among the
      elderly.

PMID- 17449481
TI  - Informal complaints on health services: hidden patterns, hidden potentials.
AB  - OBJECTIVE: To examine the prevalence of informal complaints on health services
      among clients of Health Maintenance Organizations, and explore demographic
      correlates. Such complaints are a potentially important source of information
      regarding quality of healthcare. METHOD: Primary data were collected by a phone
      survey from a nationwide random sample of 1500 persons aged 21+ in Israel.
      RESULTS: About 25% of the respondents reported a cause to complain, but only 9.5%
      actually complained. About 75% of the complainants submitted their grievances
      informally at the local level. Only a minority (17%) appealed to official bodies
      established by law. Minority groups and recent immigrants had significantly lower
      rates of reasons to complain and actual complaints. CONCLUSIONS: Suggestions are
      made for outreach efforts to socially vulnerable groups and for developing
      organizational mechanisms for capturing and using future complaints submitted
      informally to front-line employees, which are the bulk of the complaints. Further
      research is needed regarding factors affecting customers complaining and non
      complaining behavior, including factors that specifically affect the behavior of
      minority groups.

PMID- 17449482
TI  - Antimycobacterial activity of novel 1-(5-cyclobutyl-1,3-oxazol-2-yl)-3
      (sub)phenyl/pyridylthiourea compounds endowed with high activity toward multidrug
      resistant Mycobacterium tuberculosis.
AB  - OBJECTIVES: The objective of this work was to synthesize 15 new 1-(5-cyclobutyl
      1,3-oxazol-2-yl)-3-(sub)phenyl/pyridylthiourea compounds and evaluate their in
      vitro and in vivo antimycobacterial activities. METHODS: 5-Cyclobutyloxazol-2
      amine was reacted with 1,1'-thiocarbonyldiimidazole, followed by various
      substituted anilines and 2-amino pyridines to yield the 15 compounds, which were
      subjected to in vitro and in vivo evaluation against Mycobacterium tuberculosis
      H37Rv (MTB) and a clinical isolate of multidrug-resistant M. tuberculosis (MDR
      TB). RESULTS: Among the 15 compounds screened, 7 compounds inhibited both MTB and
      MDR-TB in vitro with MICs of < 1 microM. In the in vivo screening, compound 1-(5
      cyclobutyl-1,3-oxazol-2-yl)-3-(2'-trifluoromethyl)phenylthiourea (compound 8) was
      equally active as isoniazid at the same dose level. CONCLUSIONS: Compound 8 was
      found to be the most active, with an in vitro MIC of 0.14 microM and was 2.5 and
      80 times more active than isoniazid against MTB and MDR-TB, respectively.
      Compound 8 was non-toxic to Vero cells up to 183 microM, with a selectivity index
      of > 1307. In the in vivo animal model, compound 8 decreased the mycobacterium
      load in lung and spleen tissues with 2.8 and 3.94 log(10) reductions,
      respectively.

PMID- 17449483
TI  - Prevalence and determinants of transmitted antiretroviral drug resistance in HIV
      1 infection.
AB  - Transmission of drug-resistant HIV-1 variants from antiretroviral treatment
      experienced persons has been documented to occur through multiple routes,
      including sexual intercourse, intravenous drug use and vertically from mother to
      child. Newly infected persons with transmitted drug resistance (TDR) also act as
      a source for the onward transmission of resistant variants. Rates of virological
      suppression and behavioural patterns of treated populations and the relative
      fitness of drug-resistant variants are important determinants of the prevalence
      of TDR. Current estimates indicate that the prevalence is highest in regions and
      populations with long-established use of antiretroviral therapy. Limited data
      suggest that the incidence of TDR is rising in developing countries where access
      to therapy is increasing. There are methodological variations between studies,
      however, including those relative to the selection of the study population and
      the resistance interpretation system, which can skew prevalence estimates. TDR
      has important implications for the successful management of antiretroviral
      therapy. Routine resistance testing of drug-naive persons has been widely adopted
      in affluent countries and shown to effectively guide the selection of first-line
      regimens. Genotypic resistance tests offer a practical approach for detecting
      TDR. However, routine methods can only detect resistant mutants within the
      dominant quasi-species and fail to detect low-frequency resistant variants, which
      may become important once selective drug pressure is introduced. More sensitive
      testing methods are being evaluated but remain research tools at present. In
      addition, factors such as superinfection and possible differences in resistance
      patterns between plasma and cellular reservoirs and between anatomical
      compartments should be considered when evaluating TDR.

PMID- 17449484
TI  - Response to anti-tumour necrosis factor alpha blockade is associated with
      reduction of carotid intima-media thickness in patients with active rheumatoid
      arthritis.
AB  - OBJECTIVES: To determine whether tumour necrosis factor (TNF)-alpha blockers may
      reduce carotid intima-media thickness (cIMT) in patients with active rheumatoid
      arthritis (RA) steadily responsive to such therapy. METHODS: From 287 consecutive
      RA patients attending our out-patient clinic and diagnosed on the basis of the
      American College of Rheumatology (ACR) criteria, 49 without traditional
      cardiovascular risk factors and meeting the requirements for TNF-alpha blockers
      therapy were selected. Among them, 39 actually started TNF-alpha blockers, but
      only 30, who reached at least a response on the ACR 20% improvement criteria at
      14 weeks, maintained during the whole year of treatment, were finally considered
      (group A). The remaining 10/49, homogeneous for age, sex, traditional
      cardiovascular risk factors, socioeconomic status, disease activity and duration,
      who did not consent to TNF-alpha-blocker administration, were used as controls
      (group B). Disease activity score in 44 joints (DAS44), erythrocyte sedimentation
      rate (ESR) and C-reactive protein (CRP) were evaluated before starting the study,
      and 3, 6, 12 months thereafter; cIMT was measured by ultrasound before and 12
      months thereafter only. RESULTS: Patients in group A showed a very significant
      cIMT reduction (P < 0.0001 and P < 0.0001, on the right and left side,
      respectively), preceded by an early and lasting significant decrease in DAS44,
      ESR and CRP. Moreover, a significant correlation was found between cIMT and DAS44
      (r = 0.435, P < 0.05). CONCLUSIONS: These results demonstrate that TNF-alpha
      blockade is associated with cIMT reduction in RA patients steadily responsive to
      therapy, probably by lowering inflammation.

PMID- 17449485
TI  - Do Tc-99m-diphosphonate bone scans have any place in the investigation of
      polyarthralgia?

PMID- 17449486
TI  - Electrocardiographic abnormalities in infants born from mothers with autoimmune
      diseases--a multicentre prospective study.
AB  - OBJECTIVES: To assess the prevalence of congenital heart block (CHB) and
      electrocardiographic (ECG) abnormalities in infants of anti-Ro/SSA-positive
      women. METHODS: Sixty anti-Ro-positive and 36 anti-Ro-negative patients were
      prospectively followed before/during pregnancy and underwent weekly fetal
      echocardiography from 18th to 26th weeks of gestational age. Infants' ECG and/or
      ECG-Holter were performed at 1, 3, 6 and 12 months. ECG of 200 consecutive
      neonates were used as a healthy control group. RESULTS: One of 61 fetuses of anti
      Ro-positive mothers developed CHB (20th week); another anti-Ro-positive baby
      developed second degree atrioventricular (AV) block (30th week). The prevalence
      of transient first degree AV block detected post-natally was significantly higher
      in the anti-Ro-positive group, in comparison with healthy controls (P = 0.002).
      No differences in corrected QT (QTc) interval prolongation prevalence (>/=440 ms)
      was observed between the anti-Ro-positive and -negative groups, but both were
      significantly higher than that of the control population (P < 0.001). ECG-Holter
      showed QTc prolongation in 59% of infants of anti-Ro-positive and in 60% of
      infants of anti-Ro-negative mothers. Holter QTc was >/=470 ms in four infants of
      anti-Ro-positive group and two of anti-Ro-negative group. Known acquired causes
      of QTc prolongation were excluded. CONCLUSIONS: This prospective study confirms
      the low occurrence of CHB in newborns from anti-Ro-positive mothers. ECG
      abnormalities (first degree AV block and QTc interval prolongation) are frequent
      in infants of mothers with autoimmune diseases, independently of maternal
      disease, autoantibody profile and treatment during pregnancy.

PMID- 17449487
TI  - Adult-onset Still's disease and myocarditis: successful treatment with
      intravenous immunoglobulin and maintenance of remission with etanercept.

PMID- 17449488
TI  - The common-sense model of self-regulation of health and illness: how can we use
      it to understand and respond to our patients' needs?

PMID- 17449489
TI  - Efficacy of the IL-1 receptor antagonist, anakinra, for the treatment of diffuse
      anterior scleritis in rheumatoid arthritis. Report of two cases.

PMID- 17449490
TI  - Schnitzler's syndrome--exacerbation after anti-TNF treatment.

PMID- 17449491
TI  - Contrast media nephropathy--how to diagnose and how to prevent?

PMID- 17449492
TI  - Expression of IL-19 correlates with Th2 cytokines in uraemic patients.
AB  - BACKGROUND: Patients with end-stage renal disease are thought to be in a chronic
      state of inflammation. They also have an impaired immune response with a
      dysregulated Th1/Th2 cytokine network. Interleukin (IL)-19, which belongs to the
      IL-10 family, is a newly discovered proinflammatory cytokine. IL-19 alters the
      balance of Th1/Th2 cells in favour of Th2. The aims of the present study were to
      assess the changes in serum levels of IL-19 and their correlation with Th2
      cytokine production in uraemic patients. METHODS: Seventy-three uraemic patients
      with haemodialysis were evaluated; 33 healthy volunteers served as controls.
      Serum levels of IL-19, -4, -5, -6, -10, -13 and tumour necrosis factor (TNF)
      alpha were analysed using ELISA. Monocytes and T cells isolated from the patients
      and healthy volunteers were cultured in vitro, and cytokine production was
      determined. RESULTS: IL-19 expression in the patients; but not in healthy
      controls, correlated positively with both the proinflammatory cytokines (IL-6 and
      TNF-alpha) and the Th2 cytokines (IL-4, IL-5, IL-6, IL-10 and IL-13). Cultured
      monocytes from patients with high IL-19 serum levels produced more IL-19 in
      vitro. Additionally, uraemic serum or oxidized low-density lipoproteins up
      regulated the IL-19 transcripts expression in resting monocytes. Compared with T
      cells from healthy controls, uraemic T cells expressed more endogenous Th2
      cytokine transcripts and further responded to IL-19 stimulation in Th2 cytokine
      production in vitro. CONCLUSIONS: IL-19 expression in uraemic patients correlated
      with Th2 immune responses which might be involved in the cytokine dysregulation
      in uraemia.

PMID- 17449493
TI  - Can calcimimetics inhibit parathyroid hyperplasia? Evidence from preclinical
      studies.

PMID- 17449494
TI  - Pyridoxal phosphate prevents progression of diabetic nephropathy.
AB  - BACKGROUND: We have demonstrated that pyridoxal 5'-phosphate (PLP), an active
      form of vitamin B6, inhibits formation of advanced glycation end-products (AGEs)
      by trapping 3-deoxyglucosone. The present study aimed to clarify if PLP could
      exert beneficial effects on nephropathy in diabetic rats. METHODS: Streptozotocin
      (STZ)-induced diabetic rats were treated by oral administration of PLP or
      pyridoxamine (PM), another active form of vitamin B6, at a dose of 600 mg/kg/day
      for 16 weeks. AGEs [imidazolone, N(epsilon)-(carboxymethyl)lysine (CML) and N(2)
      carboxyethyl-2'-deoxyguanosine (CEdG)], transforming growth factor-beta1 (TGF
      beta1), type 1 collagen and fibronectin were detected in the kidneys using
      immunohistochemistry. Gene expression of TGF-beta1 and receptor for AGEs (RAGEs)
      in the kidneys was determined using real-time quantitative polymerase chain
      reaction. RESULTS: Administration of PLP significantly inhibited albuminuria,
      glomerular hypertrophy, mesangial expansion, and interstitial fibrosis as
      compared with diabetic rats. PLP markedly inhibited accumulation of AGEs such as
      imidazolone, CML and CEdG, a DNA-linked AGE, in glomeruli. PLP significantly
      inhibited expression of TGF-beta1, type 1 collagen, fibronectin and RAGE in the
      kidneys. PLP was superior to PM in inhibiting accumulation of AGEs, expression of
      TGF-beta1, type 1 collagen, and fibronectin, and the development of diabetic
      nephropathy. CONCLUSIONS: PLP prevented progression of nephropathy in STZ-induced
      diabetic rats by inhibiting formation of AGEs. PLP is considered a promising
      active form of vitamin B6 for the treatment of AGE-linked disorders such as
      diabetic nephropathy.

PMID- 17449495
TI  - Cinacalcet is effective in relapses of secondary hyperparathyroidism after
      parathyroidectomy.
AB  - BACKGROUND: Relapses of secondary hyperparathyroidism (SHPTH) after
      parathyroidectomy (PTx) in haemodialysis patients are relatively frequent.
      Calcimimetics (cinacalcet HCl) offer a new therapeutic opportunity for their
      treatment. However, no data about the treatment with cinacalcet of relapses of
      SHPTH after PTx are available in literature. The aim of this single-centre
      prospective study was to evaluate the therapeutic efficacy of cinacalcet in this
      high-risk category of patients. METHODS: Twelve haemodialysis patients of our
      Dialysis Unit had a relapse of SHPTH after PTx, defined as serum levels of
      immunoreactive intact parathyroid hormone (iPTH)>300 pg/ml. They were stratified
      into a treatment group (the six patients having the highest serum levels of iPTH)
      and a control group (the remaining six patients): the former were treated for 6
      months with a dose of cinacalcet ranging from 30 mg every other day to 60 mg a
      day; the latter continued to be administered the conventional treatment. Serum
      levels of albumin, iPTH, calcium (Ca), phosphate (P) and alkaline phosphatase
      were determined monthly. The treatment group included four cases of nodular
      hyperplasia and two cases of carcinoma of parathyroid glands, whereas the control
      group included four cases of nodular hyperplasia and two cases of diffuse
      hyperplasia. RESULTS: At the start of the study, the six patients treated with
      cinacalcet showed a more severe picture of biochemical abnormalities when
      compared with the control patients. After 6 months of treatment, a statistically
      significant reduction in the serum levels of iPTH, Ca, P and CaxP product was
      obtained only in the patients treated with cinacalcet. Symptomatic episodes of
      hypocalcaemia (serum Ca<7.0 mg/dl) were observed in three patients of this group.
      The six patients undergoing the conventional treatment showed at 6 months a not
      significant decrease in the mean serum levels of iPTH and a not significant
      increase in the mean serum levels of Ca, P and CaxP product, when compared with
      the baseline values. CONCLUSIONS: Our single-centre prospective study, even
      though small and of short duration, shows that cinacalcet is effective also in
      controlling relapses of SHPTH after PTx, thus representing a solid, and sometimes
      unique, therapeutic opportunity for this high-risk category of patients.

PMID- 17449496
TI  - Familial nephrotic syndrome: PLCE1 enters the fray.

PMID- 17449497
TI  - Insulin maintains plasma antioxidant capacity at an early phase of kidney
      transplantation.
AB  - BACKGROUND: Ischaemia-reperfusion and hyperglycaemia are two main sources of
      oxidative stress that plays an important role in the pathophysiology of tissue
      injury in transplant recipients. We hypothesized that controlling hyperglycaemia
      with insulin during the first hours following kidney transplantation could
      improve antioxidant defences and therefore decrease ischaemia-reperfusion-induced
      injury. METHOD: We performed a prospective randomized study in non-diabetic
      dialysed patients receiving a first cadaveric renal allograft, and assigned them
      to receive either 200 g/day of glucose infusion (control group, n=23) or the same
      glucose infusion and intravenous insulin to maintain blood glucose<10 mmol/l
      (insulin group, n=20). Antioxidant defences were assessed by the plasma total
      radical-trapping antioxidant parameter (TRAP). RESULTS: TRAP values remained
      stable throughout the study in the Insulin group, whereas they decreased from
      admission to day 1 (-2.70+/-0.16 vs -2.98+/-0.26, P<0.0001), and tended to
      retrieve the basal values at day 15 in the control group. TRAP values were
      significantly higher in the insulin group compared with the control group at days
      1 (-2.80+/-0.19 vs -2.98+/-0.16, P<0.05) and 4 (-2.80+/-0.19 vs -2.95+/-0.20,
      P<0.05). No differences were found between the two groups on urinary
      malondialdehyde determination, two markers of oxidative damage, nor in graft
      function or patient outcome. CONCLUSIONS: This is the first clinical trial to
      demonstrate improvement in insulin-induced antioxidant defences at the early
      stage of kidney transplantation. More extensive studies will tell if this
      strategy has beneficial impact in long-term graft outcome.

PMID- 17449498
TI  - Changes in growth and activity of enzymes involved in nitrate reduction and
      ammonium assimilation in tomato seedlings in response to NaCl stress.
AB  - BACKGROUND AND AIMS: In Tunisia, salt water is largely used for tomato
      irrigation. In this work, a study was made of the changes in the nitrate
      reduction and ammonium assimilation into amino acids in tomato seedlings under
      salinity in order to providee further insight into the salt effects on plant
      growth. Methods Ten-day-old tomatoes (Solanum lycopersicum) were subjected to 100
      mm NaCl stress, and nitrogen metabolism in leaves and roots was studied. KEY
      RESULTS: The concentrations of Na+ and Cl- rapidly increased in the leaves and in
      the roots following exposure of tomato seedlings to NaCl stress. In contrast, the
      NO3- concentrations were lowered first in the roots and later in the leaves. From
      5 to 10 d of treatment, salt ions provoked a decrease in the dry weight and an
      increase in the NH4+ concentrations in the leaves. Inhibition was observed in the
      leaves for the activities of nitrate reductase (NR, EC 1.6.6.1), ferredoxin
      dependent glutamate synthase (Fd-GOGAT, EC 1.4.7.1) and deaminating glutamate
      dehydrogenase (NAD-GDH, EC 1.4.1.2). NaCl affected these enzyme activities less
      in the roots than in leaves. This was in accordance with the pronounced decrease
      of dry weight by salt in leaves compared with that in the roots. CONCLUSIONS:
      NaCl stress effects on growth, metabolite concentrations and enzyme activities
      depended on the duration of salt treatment and the plant tissue.

PMID- 17449499
TI  - Remote ischaemic postconditioning protects the heart during acute myocardial
      infarction in pigs.
AB  - BACKGROUND: Ischaemic preconditioning results in a reduction in ischaemic
      reperfusion injury to the heart. This beneficial effect is seen both with direct
      local preconditioning of the myocardium and with remote preconditioning of easily
      accessible distant non-vital limb tissue. Ischaemic postconditioning with a
      comparable sequence of brief periods of local ischaemia, when applied immediately
      after the ischaemic insult, confers benefits similar to preconditioning.
      OBJECTIVE: To test the hypothesis that limb ischaemia induces remote
      postconditioning and hence reduces experimental myocardial infarct size in a
      validated swine model of acute myocardial infarction. METHODS: Acute myocardial
      infarction was induced in 24 pigs with 90 min balloon inflations of the left
      anterior descending coronary artery. Remote ischaemic postconditioning was
      induced in 12 of the pigs by four 5 min cycles of blood pressure cuff inflation
      applied to the lower limb immediately after the balloon deflation. Infarct size
      was assessed by measuring 72 h creatinine kinase release, MRI scan and
      immunohistochemical analysis. RESULTS: Area under the curve of creatinine kinase
      release was significantly reduced in the postconditioning group compared with the
      control group with a 26% reduction in the infarct size (p<0.05). This was
      confirmed by MRI scanning and immunohistochemical analysis that revealed a 22%
      (p<0.05) and a 47.52% (p<0.01) relative reduction in the infarct size,
      respectively. CONCLUSION: Remote ischaemic postconditioning is a simple technique
      to reduce infarct size without the hazards and logistics of multiple coronary
      artery balloon inflations. This type of conditioning promises clear clinical
      potential.

PMID- 17449500
TI  - Use of intravenous magnesium to treat acute onset atrial fibrillation: a meta
      analysis.
AB  - OBJECTIVES: To assess the effects of intravenous magnesium on converting acute
      onset atrial fibrillation to sinus rhythm, reducing ventricular response and risk
      of bradycardia. DESIGN AND DATA SOURCES: Randomised controlled trials evaluating
      intravenous magnesium to treat acute onset atrial fibrillation from MEDLINE (1966
      to 2006), EMBASE (1990 to 2006) and Cochrane Controlled Trials Register without
      language restrictions. REVIEW METHODS: Two researchers independently performed
      the literature search and data extraction. RESULTS: 10 randomised controlled
      trials, including a total of 515 patients with acute onset atrial fibrillation,
      were considered. Intravenous magnesium was not effective in converting acute
      onset atrial fibrillation to sinus rhythm when compared to placebo or an
      alternative antiarrhythmic drug. When compared to placebo, adding intravenous
      magnesium to digoxin increased the proportion of patients with a ventricular
      response <100 beats/min (58.8% vs 32.6%; OR 3.2, 95% CI 1.93 to 5.42; p<0.001).
      When compared to calcium antagonists or amiodarone, intravenous magnesium was
      less effective in reducing the ventricular response (21.4% vs 58.5%; OR 0.19, 95%
      CI 0.09 to 0.44; p<0.001) but also less likely to induce significant bradycardia
      or atrioventricular block (0% vs 9.2%; OR 0.13, 95% CI 0.02 to 0.76; p = 0.02).
      The use of intravenous magnesium was associated with transient minor symptoms of
      flushing, tingling and dizziness in about 17% of the patients (OR 14.5, 95% CI
      3.7 to 56.7; p<0.001). CONCLUSIONS: Adding intravenous magnesium to digoxin
      reduces fast ventricular response in acute onset atrial fibrillation. The effect
      of intravenous magnesium on the ventricular rate and its cardiovascular side
      effects are less significant than other calcium antagonists or amiodarone.
      Intravenous magnesium can be considered as a safe adjunct to digoxin in
      controlling the ventricular response in atrial fibrillation.

PMID- 17449501
TI  - Postprocedural single-lead ST-segment deviation and long-term mortality in
      patients with ST-segment elevation myocardial infarction treated by primary
      angioplasty.
AB  - OBJECTIVE: To evaluate the prognostic role of postprocedural single-lead residual
      ST-segment deviation for electrocardiographic evaluation of myocardial perfusion
      in patients with ST-segment elevation myocardial infarction (STEMI) treated by
      primary angioplasty. DESIGN: Prospective observational clinical cohort study.
      SETTING: Tertiary referral centre. PATIENTS: 1660 patients treated with primary
      angioplasty for STEMI. MAIN OUTCOME MEASURE: Mortality at 1-year follow-up.
      RESULTS: Single-lead ST-segment deviation significantly correlated with infarct
      size, predischarge ejection fraction, distal embolisation and myocardial blush
      grade 3. At 1-year follow-up, 63 patients had died. The method correlated well
      with 1-year mortality. At multivariate analysis, after correction for baseline
      demographic, clinical and angiographic variables, postprocedural single-lead ST
      segment deviation showed better accuracy than residual single-lead ST-segment
      elevation or resolution and residual 12-lead ST-segment deviation. CONCLUSIONS:
      This study showed that maximal residual ST-segment deviation in a single lead at
      3 hours after the procedure is an easy and accurate predictor of 1-year mortality
      after primary angioplasty for STEMI.

PMID- 17449502
TI  - Sirolimus and paclitaxel provoke different vascular pathological responses after
      local delivery in a murine model for restenosis on underlying atherosclerotic
      arteries.
AB  - BACKGROUND: Drug-eluting stents (DES) have been introduced successfully in
      clinical practice to prevent post-angioplasty restenosis. Nevertheless, concerns
      about the safety of DES still exist. OBJECTIVE: To investigate the vascular
      pathology and transcriptional responses to sirolimus and paclitaxel in a murine
      model for restenosis on underlying diseased atherosclerotic arteries. METHODS:
      Atherosclerotic lesions were induced by placement of a perivascular cuff around
      the femoral artery of hypercholesterolaemic ApoE*3-Leiden transgenic mice. Two
      weeks later these cuffs were replaced either by sirolimus- or paclitaxel-eluting
      cuffs. The vascular pathological effects were evaluated after two additional
      weeks. RESULTS: Both anti-restenotic compounds significantly inhibited restenotic
      lesion progression on the atherosclerotic plaques. Vascular histopathological
      analyses showed that local delivery of sirolimus has no significant adverse
      effects on vascular disease. Conversely, high dosages of paclitaxel significantly
      increased apoptosis, internal elastic lamina disruption, and decreased medial and
      intimal smooth muscle cells and collagen content. Moreover, transcriptional
      analysis by real-time RT-PCR showed an increased level of pro-apoptotic mRNA
      transcripts (FAS, BAX, caspase 3) in paclitaxel-treated arteries. CONCLUSIONS:
      Sirolimus and paclitaxel are effective in preventing restenosis. Sirolimus has no
      significant effect on arterial disease. In contrast, paclitaxel at high
      concentration demonstrated adverse vascular pathology and transcriptional
      responses, suggesting a narrower therapeutic range of this potent drug. Since the
      use of overlapping stents is becoming more common in DES technology, this factor
      is important, given that higher dosages of paclitaxel may lead to increased
      apoptosis in the vessel wall and, consequently, to a more unstable phenotype of
      the pre-existing atherosclerotic lesion.

PMID- 17449503
TI  - Abnormal left ventricular longitudinal functional reserve in patients with
      diabetes mellitus: implication for detecting subclinical myocardial dysfunction
      using exercise tissue Doppler echocardiography.
AB  - BACKGROUND: Subclinical myocardial dysfunction occurs in a significant number of
      patients with type 2 diabetes. Assessment of ventricular long-axis function by
      measuring mitral annular velocities using tissue Doppler echocardiography (TDE)
      is thought to provide a more sensitive index of systolic and diastolic function.
      We hypothesised that augmentation of left ventricular (LV) longitudinal
      contraction and relaxation during exercise would be blunted in patients with type
      2 diabetes. METHODS: Mitral annular systolic (S') and early diastolic (E')
      velocities were measured at rest and during supine bicycle exercise (25 W, 3 min
      increments) in 53 patients (27 male, mean age 53+/-14 years) with type 2 diabetes
      and 53 subjects with age and gender-matched control. None had echocardiographic
      evidence of resting or inducible myocardial ischaemia. RESULTS: There were no
      significant differences in mitral inflow velocities at rest between the two
      groups. E' and S' at rest were also similar between the groups. However, S'
      (7.1+/-1.3 vs 8.3+/-1.8 cm/s at 25 W, p = 0.0021; 8.1+/-1.5 vs 9.1+/-2.0 cm/s at
      50 W, p = 0.026) and E' (8.5+/-2.3 vs 9.9+/-3.1 cm/s at 25 W, p = 0.054; 9.1+/
      2.1 vs 10.9+/-2.5 cm/s at 50 W, p = 0.0093) during exercise were significantly
      lower in patients with diabetes compared with controls. Longitudinal systolic and
      diastolic function reserve indices were significantly lower in patients with
      diabetes compared with that of controls (systolic index, 0.6+/-0.70 vs 1.2+/-1.5
      cm/s at 25 W, p = 0.029; 1.2+/-1.2 vs 2.1+/-1.6 cm/s at 50 W, p = 0.009;
      diastolic index, 1.9+/-1.2 vs 2.5+/-2.2 cm/s at 25 W, p = 0.07; 2.3+/-1.3 vs
      3.2+/-2.2 cm/s at 50 W, p = 0.031). CONCLUSION: In conclusion, unlike resting
      mitral inflow and annular velocities, changes of systolic and diastolic
      velocities of the mitral annulus during exercise were significantly reduced in
      patients with type 2 diabetes compared with the control group. The assessment of
      LV longitudinal functional reserve with exercise using TDE appears to be helpful
      in identifying early myocardial dysfunction in patients with type 2 diabetes.

PMID- 17449504
TI  - "I haven't even phoned my doctor yet." The advice giving role of the pharmacist
      during consultations for medication review with patients aged 80 or more:
      qualitative discourse analysis.
AB  - OBJECTIVE: To explore the advice giving role of pharmacists during consultation
      for medication review with patients aged 80 or more. DESIGN: Discourse analysis.
      SETTING: Participants' homes. PARTICIPANTS: Subsample of consultations within a
      large randomised trial of home medication review among patients aged 80 or more
      who had been admitted to hospital. MAIN OUTCOME MEASURES: Extent to which advice
      given by pharmacists was accepted and acknowledged by patients. RESULTS:
      Pharmacists found many opportunities to offer advice, information, and
      instruction. These advice giving modes were rarely initiated by the patients and
      were given despite a no problem response and deliberate displays of competence
      and knowledge by patients. Advice was often resisted or rejected and created
      interactional difficulties and awkward moments during the consultations.
      CONCLUSIONS: The advice giving role of pharmacists during consultations with
      patients aged 80 or more has the potential to undermine and threaten the
      patients' assumed competence, integrity, and self governance. Caution is needed
      in assuming that commonsense interventions necessarily lead to health gain.

PMID- 17449505
TI  - Cognitive behaviour therapy to prevent complicated grief among relatives and
      spouses bereaved by suicide: cluster randomised controlled trial.
AB  - OBJECTIVE: To examine the effectiveness of a family based grief counselling
      programme to prevent complicated grief among first degree relatives and spouses
      of someone who had committed suicide. DESIGN: Cluster randomised controlled trial
      with follow-up at 13 months after the suicide. SETTING: General practices in the
      Netherlands. PARTICIPANTS: 122 first degree relatives and spouses of 70 people
      who committed suicide; 39 families (68 participants) were allocated to
      intervention, 31 families (54 participants) to control. INTERVENTION: A family
      based, cognitive behaviour counselling programme of four sessions with a trained
      psychiatric nurse counsellor between three to six months after the suicide.
      Control participants received usual care. MAIN OUTCOME MEASURES: Self report
      complicated grief. Secondary outcomes were the presence of maladaptive grief
      reactions, depression, suicidal ideation, and perceptions of being to blame for
      the suicide. RESULTS: The intervention was not associated with a reduction in
      complicated grief (mean difference -0.61, 95% confidence interval -6.05 to 4.83;
      P=0.82). Secondary outcomes were not affected either. When adjusted for baseline
      inequalities, the intervention reduced the risk of perceptions of being to blame
      (odds ratio 0.18, 0.05 to 0.67; P=0.01) and maladaptive grief reactions (0.39,
      0.15 to 1.01; P=0.06). CONCLUSIONS: A cognitive behaviour grief counselling
      programme for families bereaved by suicide did not reduce the risk of complicated
      grief or suicidal ideation or the level of depression. The programme may help to
      prevent maladaptive grief reactions and perceptions of blame among first degree
      relatives and spouses. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN66473618.

PMID- 17449507
TI  - Intermittent fasciculoventricular pathway: ECG and electrophysiologic findings,
      clinical implications.
AB  - Although fasciculoventricular (FV) pathways never participate into tachycardia
      circuits, they give rise to ventricular pre-excitation of variable magnitude
      which can be source of ECG misinterpretation when associated to other
      supraventricular rhythm disorders. We report an intermittent FV pathway
      coincidentally unmasked during an electrophysiologic study performed for a
      symptomatic supraventricular tachycardia (atrial tachycardia). The clinical
      context, ECG and EP findings, and therapeutic options are described.
      Fasciculoventricular pathways need no medical or ablative treatment, thus their
      positive and differential diagnosis must be clearly assessed.

PMID- 17449506
TI  - Long term effects of dietary sodium reduction on cardiovascular disease outcomes:
      observational follow-up of the trials of hypertension prevention (TOHP).
AB  - OBJECTIVE: To examine the effects of reduction in dietary sodium intake on
      cardiovascular events using data from two completed randomised trials, TOHP I and
      TOHP II. DESIGN: Long term follow-up assessed 10-15 years after the original
      trial. SETTING: 10 clinic sites in 1987-90 (TOHP I) and nine sites in 1990-5
      (TOHP II). Central follow-up conducted by post and phone. PARTICIPANTS: Adults
      aged 30-54 years with prehypertension. INTERVENTION: Dietary sodium reduction,
      including comprehensive education and counselling on reducing intake, for 18
      months (TOHP I) or 36-48 months (TOHP II). MAIN OUTCOME MEASURE: Cardiovascular
      disease (myocardial infarction, stroke, coronary revascularisation, or
      cardiovascular death). RESULTS: 744 participants in TOHP I and 2382 in TOHP II
      were randomised to a sodium reduction intervention or control. Net sodium
      reductions in the intervention groups were 44 mmol/24 h and 33 mmol/24 h,
      respectively. Vital status was obtained for all participants and follow-up
      information on morbidity was obtained from 2415 (77%), with 200 reporting a
      cardiovascular event. Risk of a cardiovascular event was 25% lower among those in
      the intervention group (relative risk 0.75, 95% confidence interval 0.57 to 0.99,
      P=0.04), adjusted for trial, clinic, age, race, and sex, and 30% lower after
      further adjustment for baseline sodium excretion and weight (0.70, 0.53 to 0.94),
      with similar results in each trial. In secondary analyses, 67 participants died
      (0.80, 0.51 to 1.26, P=0.34). CONCLUSION: Sodium reduction, previously shown to
      lower blood pressure, may also reduce long term risk of cardiovascular events.

PMID- 17449508
TI  - Normalization of the vagina by dilator treatment alone in Complete Androgen
      Insensitivity Syndrome and Mayer-Rokitansky-Kuster-Hauser Syndrome.
AB  - BACKGROUND: Various surgical and non-surgical treatment options are available for
      women with congenital vaginal agenesis. We report results of vaginal dilation
      therapy delivered by a multi-disciplinary team as first line treatment for
      vaginal agenesis. METHODS: Twenty-six women were recruited into a prospective
      observational study: 18 had Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) and 8
      had Complete Androgen Insensitivity Syndrome (CAIS). All women underwent a
      vaginal dilation programme co-ordinated by a clinical nurse specialist with input
      from a clinical psychologist. Vaginal length was compared to a normal reference
      range, and psycho-sexual questionnaires were completed before and after therapy.
      RESULTS: Twenty-one (81%) patients completed the programme. Seventeen of these 21
      (81%) were sexually active without any reported difficulties, whereas 4 were on a
      maintenance regime. In those who completed the programme the mean vaginal length
      increased from 4.0 to 8.5 cm and 86% achieved a vaginal length within the normal
      range. Subjective appraisal of vaginal size recorded that the number of women who
      reported that their vaginal size was 'more or less normal' increased from 1 to 12
      following treatment. Questionnaire scores for sexual satisfaction and sexual
      depression improved in the CAIS group but did not alter significantly in the MRKH
      group. CONCLUSION: Non-surgical dilation delivered by a multi-disciplinary team
      is an effective alternative to vaginal surgery and usually normalizes vaginal
      length.

PMID- 17449509
TI  - The length of the fertile window is associated with the chance of spontaneously
      conceiving an ongoing pregnancy in subfertile couples.
AB  - BACKGROUND: The period in each menstrual cycle during which sexual intercourse
      can result in conception is called the "fertile window". Although the fertile
      window closes on the day of ovulation, little is known about the moment it opens.
      We defined the first day of normal sperm-mucus interaction as the opening of the
      fertile window. We hypothesized that length of the fertile window varies between
      couples and that the number of days the fertile window is "open" is related to
      the time to spontaneous conception. METHODS Serial post-coital tests and sperm
      mucus penetration tests were performed to detect the first normal sperm-mucus
      interaction day. Ovulation was confirmed by serial ultrasound. Using Cox'
      regression analysis, we determined whether the fertile window length was
      associated with time to ongoing pregnancy. This association was expressed in
      fecundability ratios (FR). RESULTS The fertile window length was determined in
      410 subfertile couples. The fertile window length varied among couples from <1 to
      >5 days. The FR increased with increasing fertile window length and varied
      between 0.11 (95% CI: 0.03-0.45) for a fertile window of 1 day, to 2.4 (95% CI:
      1.1-5.2) for a fertile window of 5 days or more. CONCLUSIONS The longer the
      fertile window in subfertile couples, the higher is the probability of
      spontaneously conceiving an ongoing pregnancy.

PMID- 17449510
TI  - Reproductive outcomes of women with a previous history of Caesarean scar ectopic
      pregnancies.
AB  - BACKGROUND: Caesarean scar ectopic pregnancy is associated with a number of
      significant complications. In this study, we report on subsequent reproductive
      outcomes in a group of women following successful treatment of their scar
      pregnancies. METHODS: The study included those women who received treatment for
      their Caesarean scar pregnancies between April 1999 and October 2005. Their
      ability to conceive, the time it took to become pregnant and outcomes of
      subsequent pregnancies were all recorded. RESULTS: 40 women with Caesarean scar
      pregnancies were managed in our unit. The uterus was conserved in 38/40 cases.
      Follow-up data were available in 29/38 (76%) of women. Twenty-four out of 29
      (83%) attempted to become pregnant. Twenty-one out of 24 [88%, 95% confidence
      interval (CI): 75-100] women conceived spontaneously. Twenty out of 21 (95%, 95%
      CI: 86-100) pregnancies were intrauterine and one woman (5%, 95% CI: 0-14) had a
      recurrent scar ectopic. Thirteen out of 20 (65%, 95% CI: 44-86) intrauterine
      pregnancies appeared normal. Nine out of 13 (69%) were delivered by Caesarean
      section. Seven out of 20 (35%, 95% CI: 14-56) intrauterine pregnancies ended in
      spontaneous abortions. CONCLUSIONS: Our study shows that reproductive outcomes
      following treatment of caesarean scar ectopic pregnancies are favourable. The
      risk of complications including recurrent scar implantation appears to be low.

PMID- 17449511
TI  - Highly purified FSH is as efficacious as recombinant FSH for ovulation induction
      in women with WHO Group II anovulatory infertility: a randomized controlled non
      inferiority trial.
AB  - BACKGROUND: The objective of this study was to demonstrate non-inferiority of a
      highly purified urinary follicle stimulating hormone (HP-FSH) preparation
      compared with a recombinant (rFSH) preparation with respect to ovulation rate
      (primary end-point). METHODS: This was a randomized, open-label, assessor-blind,
      multinational study. Women with anovulatory infertility WHO Group II and
      resistant to clomiphene citrate were randomized (computer-generated list) to
      stimulation with HP-FSH (n=73) or rFSH (n=78) using a low-dose step-up protocol.
      The non-inferiority limit was prespecified at -20%. RESULTS: The ovulation rate
      was 85.2% (51/62) with HP-FSH and 90.9% (60/66) with rFSH (per-protocol
      population), and non-inferiority was demonstrated [95% confidence interval: 
      16.9; 5.6]. No differences were noted between groups in number of follicles>or=12
      mm, >or=15 mm or >or=18 mm, mono-follicular development, pregnancy rates,
      endometrial thickness, number of ovarian stimulation syndrome cases or frequency
      of injection site reactions/pain. The singleton live birth rate was 15% in both
      groups (11/73 with HP-FSH and 12/78 with rFSH). CONCLUSIONS: This urinary HP-FSH
      preparation is non-inferior compared with a rFSH preparation with respect to
      ovulation rate in anovulatory WHO Group II women failing to ovulate or conceive
      on clomiphene citrate.

PMID- 17449512
TI  - Low mitochondrial DNA and ATP contents contribute to the absence of birefringent
      spindle imaged with PolScope in in vitro matured human oocytes.
AB  - BACKGROUND: Birefrigent meiotic spindle in live human oocytes can be visualized
      by the PolScope. This study investigated the relationship between birefrigent
      meiotic spindle and cytoplasmic mitochondrial DNA (mtDNA) and ATP contents in in
      vitro matured human oocytes. METHODS: Oocytes at germinal vesicle stage were
      collected and cultured for 24-48 h with or without the metabolic inhibitor,
      carbonyl cyanide p-(tri-fluromethoxy) phenyl-hydrazone (FCCP). All in vitro
      matured oocytes were examined by PolScope for the presence of meiotic spindle,
      then the oocytes were used for either intracytoplasmic sperm injection or the
      measurement of mitochondrial quantity and ATP content. RESULTS: Meiotic spindles
      were observed in 51.3% (60/117) of the in vitro matured oocytes. Oocytes with
      detectable meiotic spindle contained significantly higher mtDNA copies (637 250
      +/- 237 606 versus 491 454 +/- 153 406, P = 0.027) and ATP content (1.97 +/- 0.38
      versus 1.65 +/- 0.32 pmol, P = 0.028) when compared with those without detectable
      meiotic spindle. However, in vitro matured oocytes showed a significantly reduced
      rate of positive meiotic spindle and a lower ATP content when cultured with FCCP.
      A lower incidence of normal fertilization and good quality embryos were observed
      if meiotic spindles were not detected. CONCLUSIONS: Low mtDNA and ATP content
      might contribute to the absence of birefringent spindle imaged with the PolScope
      in human in vitro matured oocytes.

PMID- 17449513
TI  - UK gamete donors' reflections on the removal of anonymity: implications for
      recruitment.
AB  - BACKGROUND: In 2005, UK legislation was changed requiring any donor of gametes or
      embryos used in the treatment of others to agree to the disclosure of their
      identity to any offspring reaching the age of 18. METHODS AND RESULTS: This paper
      analyses responses of a survey of existing donors' views on the removal of donor
      anonymity that was undertaken by the Department of Health (UK) as part of its
      review that preceded changes to the law on donor anonymity. The survey provides
      an insight into what it is about the loss of anonymity that some donors find
      problematic, indicating that although some donors will be reluctant to donate
      under conditions of non-anonymity, others have concerns about the removal of
      anonymity that can be addressed. CONCLUSIONS: This paper identifies factors, in
      particular counselling, support and better information that could maintain gamete
      donor recruitment in the context of the UK's policy of non-anonymous and non
      remunerated donation.

PMID- 17449514
TI  - The excess in 2-5 mm follicles seen at ovarian ultrasonography is tightly
      associated to the follicular arrest of the polycystic ovary syndrome.
AB  - BACKGROUND: We previously hypothesized that the excess of 2-5 mm follicles seen
      at ovarian ultrasonography might be involved in the follicular arrest (FA) of
      polycystic ovary syndrome (PCOS), independently from the main putative
      contributors of FA, namely hyperandrogenism and hyperinsulinism. METHODS: A
      multivariate statistical analysis was applied retrospectively to clinical,
      biological and ultrasound data that were consecutively collected during 5 years
      in 457 patients with polycystic ovaries and in 188 age-matched non
      hyperandrogenic and regularly cycling controls without PCO at ultrasound.
      RESULTS: Stepwise discriminant analysis indicated that in PCOS the 2-5 mm
      follicle number (FN) gave the strongest correlation to severity of the FA,
      followed by age and then by fasting insulin level. The other variables [waist
      circumference (WC), 6-9 mm FN, serum testosterone, FSH, LH and ovarian area] were
      rejected by the analysis. Multiple linear regression indicated a significant and
      independent negative relationship between the 2-5 and 6-9 mm FN in the PCOS (r = 
      0.186, P < 0.01) and control groups (r = - 0.281, P < 0.01). In PCOS only, the 6
      9 mm FN was negatively and independently related to the WC (r = - 0.108, P <
      0.05). CONCLUSIONS: The size of the 2-5 mm follicle pool is an independent and
      important contributor to the FA of PCOS. This result could be explained by an
      exaggerated physiological inhibitory effect from this pool on the terminal
      follicle growth. The metabolic derangement of PCOS that also contributes to the
      FA would act through a different mechanism.

PMID- 17449515
TI  - Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is associated
      with a prolonged gestational age.
AB  - BACKGROUND: The timing of parturition in most mammals is thought to be linked to
      a late gestational rise in corticosteroid production by the fetal adrenal gland.
      We hypothesised that gestational age would be prolonged in our patients with
      impaired cortisol production secondary to congenital adrenal hyperplasia (CAH)
      due to 21-hydroxylase deficiency. METHODS: We compared the gestational age of
      patients affected by salt-wasting CAH due to 21-hydroxylase deficiency (born 1978
      2004; n = 31) with that of children with congenital hypothyroidism (born 1981
      2003; n = 30) and a control group of short normal children (born 1980-2002; n =
      120). Each group was compared with national (England 2002-3) and regional (2003
      4) data on gestational age from hospital episode statistics. Post-term delivery
      was defined as birth beyond 41 completed weeks. RESULTS: National statistics
      reveal a frequency of 4.4% for singleton deliveries beyond 41 weeks. In our
      region the frequency was 4.6%. In the group of children with CAH, the frequency
      of post-term delivery was 19.3% (p<0.001). In patients with congenital
      hypothyroidism, the frequency was 13.3% (p = 0.02). The proportion of short
      children who did not have a recognised endocrinopathy born post term was
      comparable to national and regional data at 6.7%. CONCLUSIONS: A prolonged
      gestation is more likely in pregnancies where the fetus has the salt-wasting form
      of CAH. This may be due to impaired cortisol production, although other changes
      in steroidogenesis may also be contributory.

PMID- 17449516
TI  - Glioblastoma in a boy with fragile X: an unusual case of neuroprotection.
AB  - Glioblastomas in children usually occur in the brainstem and are often
      untreatable and associated with an extremely poor prognosis. Such tumours may
      however occur in supratentorial locations more typically associated with adult
      gliomas, where the outcome is more variable, but still poor. We report the case
      of a boy with fragile X who also developed an inoperable midbrain glioblastoma,
      but who has survived 8 years after diagnosis.

PMID- 17449517
TI  - Pancreatic phenotype in infants with cystic fibrosis identified by mutation
      screening.
AB  - OBJECTIVE: To determine the pancreatic phenotype of infants with cystic fibrosis
      (CF) diagnosed in the first week of life by a combined immunoreactive
      trypsin/mutation screening program. DESIGN: A prospective evaluation of
      pancreatic function in infants with CF at the time of neonatal diagnosis and up
      to the age of 12. SETTING: Two different centres (Verona, Italy and Westmead,
      Australia) to enable comparison of results between two regions where <60% or > or
      =90% of patients, respectively, have at least one single DeltaF508 a mutation.
      PATIENTS: 315 children with CF including 149 at Verona and 166 at Westmead.
      INTERVENTIONS: Fat balance studies over 3-5 days and pancreatic stimulation tests
      with main outcome measures being faecal fat or pancreatic colipase secretion.
      PATIENTS with malabsorption are pancreatic insufficient (PI) or with normal
      absorption and pancreatic sufficient (PS). RESULTS: 34 infants (23%) at Verona
      and 46 (28%) at Westmead were PS at diagnosis. 15% of those with two class I, II
      or III "severe" mutations and 26/28 (93%) of those with class IV or V mutations
      were PS at this early age. Of the 80 infants with PS, 20 became PI before the age
      of 12. All 20 had two severe mutations. CONCLUSION: Neonatal mutational screening
      programs for CF are less likely to detect PS patients with non-DeltaF508
      mutations. Of PS patients who are detected, those with two severe class I, II or
      III mutations are at particularly high risk of becoming PI during early
      childhood.

PMID- 17449518
TI  - The social facilitation of food intake.

PMID- 17449519
TI  - Differing views on quality of life.

PMID- 17449520
TI  - No pain, no gain? Integrating QoL assessment in paediatrics.

PMID- 17449521
TI  - How important is continuity of care?

PMID- 17449522
TI  - Childhood obesity: should primary school children be routinely screened? A
      systematic review and discussion of the evidence.
AB  - BACKGROUND: Population monitoring has been introduced in UK primary schools in an
      effort to track the growing obesity epidemic. It has been argued that parents
      should be informed of their child's results, but is there evidence that moving
      from monitoring to screening would be effective? We describe what is known about
      the effectiveness of monitoring and screening for overweight and obesity in
      primary school children and highlight areas where evidence is lacking and
      research should be prioritised. DESIGN: Systematic review with discussion of
      evidence gaps and future research. DATA SOURCES: Published and unpublished
      studies (any language) from electronic databases (inception to July 2005),
      clinical experts, Primary Care Trusts and Strategic Health Authorities, and
      reference lists of retrieved studies. REVIEW METHODS: We included any study that
      evaluated measures of overweight and obesity as part of a population-level
      assessment and excluded studies whose primary outcome measure was prevalence.
      RESULTS: There were no trials assessing the effectiveness of monitoring or
      screening for overweight and obesity. Studies focussed on the diagnostic accuracy
      of measurements. Information on the attitudes of children, parents and health
      professionals to monitoring was extremely sparse. CONCLUSIONS: Our review found a
      lack of data on the potential impact of population monitoring or screening for
      obesity and more research is indicated. Identification of effective weight
      reduction strategies for children and clarification of the role of preventative
      measures are priorities. It is difficult to see how screening to identify
      individual children can be justified without effective interventions.

PMID- 17449523
TI  - Severity of obstructive apnoea in children with Down syndrome who snore.
AB  - Diagnostic overnight polysomnograms of 33 children with Down syndrome who snored
      were reviewed. Mean age was 4.9 years, none had had adenotonsillectomy, 91% were
      non-obese (Down syndrome specific body mass index standard deviation score (BMI
      SDS) <+2.0) and yet 97% demonstrated obstructive sleep apnoea, with an average
      apnoea hypopnoea index (AHI) of 12.9 episodes per hour (normal <1) and an average
      oxygen desaturation of 4%. A higher AHI was associated with lower minimum Spo2,
      higher Tcco2 and higher number of arousals from sleep per hour (p<0.001).
      Polysomnography should be a routine investigation for children with Down syndrome
      who snore regardless of body habitus.

PMID- 17449524
TI  - Childhood immunisation: what is the future?
AB  - Improved immunisation programmes and the development of new vaccines provide
      unprecedented opportunities to improve and sustain the health of our children.
      There are major challenges ahead in communicating the benefits of immunisation to
      all populations and in delivering vaccines to those in greatest need. In this
      review on immunisation, I have asked international opinion leaders to comment on
      the present and the future of immunisation to provide signposts for the
      narrative.

PMID- 17449525
TI  - Unusual x ray image.

PMID- 17449526
TI  - Monitoring health related quality of life in adolescents with diabetes: a review
      of measures.
AB  - Particularly in chronic conditions, monitoring health related quality of life
      (HRQoL) of adolescents in clinical practice is increasingly advocated. We set out
      to identify and review the clinical utility of available generic and diabetes
      specific HRQoL questionnaires suitable for use in adolescents with type 1
      diabetes. Four generic and five diabetes specific questionnaires were identified
      and evaluated. The responsiveness of most instruments warrants further research
      and standardisation of HRQoL measurement should be sought to facilitate
      comparisons across centres and countries. The PedsQL and the KINDL-R appear, at
      this time, to be the most suitable instruments.

PMID- 17449527
TI  - The role of communication in paediatric drug safety.
AB  - Medication errors cause substantial harm to patients, and considerable cost to
      healthcare systems. Evidence suggests that communication plays a crucial role in
      the generation, management and prevention of such incidents. This review
      identifies how paediatric medication errors can be managed, and in particular
      focuses on the pathway of steps that can operationalise the current research
      findings. Furthermore, the current data suggesting how communication can help to
      prevent errors occurring in the first place is examined. From this data, it is
      apparent that there are three domains in which communication could play an
      important preventative role: first, patient doctor communication, and second
      interprofessional communication and finally researcher/professional dialogue.
      This review is an attempt to identify the importance of communication in
      paediatric mediation safety and to allow practical application of these findings.

PMID- 17449528
TI  - Recent advances in the diagnosis of childhood tuberculosis.
AB  - Children account for a major proportion of the global tuberculosis disease
      burden, especially in endemic areas. However, the accurate diagnosis of childhood
      tuberculosis remains a major challenge. This review provides an overview of the
      most important recent advances in the diagnosis of intrathoracic childhood
      tuberculosis: (1) symptom-based approaches, including symptom-based screening of
      exposed children and symptom-based diagnosis of active disease; (2) novel immune
      based approaches, including T cell assays and novel antigen-based tests; and (3)
      bacteriological and molecular methods that are more rapid and/or less expensive
      than conventional culture techniques for tuberculosis diagnosis and/or drug
      resistance testing. Recent advances have improved our ability to diagnose latent
      infection and active tuberculosis in children, but establishing a diagnosis of
      either latent infection or active disease in HIV-infected children remains a
      major challenge, particularly in high-burden settings. Although improved access
      to diagnosis and treatment is essential, ultimately the burden of childhood
      tuberculosis is determined by the level of epidemic control achieved in a
      particular community. Several recent initiatives, in particular the United
      Nations Millennium Developmental Goals, deal with the problem of poverty and
      disease in a holistic fashion, but global political commitment is required to
      support these key initiatives.

PMID- 17449529
TI  - Treating severe acute malnutrition seriously.
AB  - Severe acute malnutrition (SAM) affects approximately 13 million children under
      the age of 5 and is associated with 1-2 million preventable child deaths each
      year. In most developing countries, case fatality rates (CFRs) in hospitals
      treating SAM remain at 20-30% and few of those requiring care actually access
      treatment. Recently, community-based therapeutic care (CTC) programmes treating
      most cases of SAM solely as outpatients have dramatically reduced CFRs and
      increased the numbers receiving care. CTC uses ready-to-use therapeutic foods and
      aims to increase access to services, promoting early presentation and compliance,
      thereby increasing coverage and recovery rates. Initial data indicate that this
      combination of centre-based and community-based care is cost effective and should
      be integrated into mainstream child survival programmes.

PMID- 17449530
TI  - Experiencing Guillain Barre: a mother and daughter perspective.

PMID- 17449531
TI  - Is hyperchloraemic acidosis a problem in children with gastroenteritis rehydrated
      with normal saline? Authors' reply.

PMID- 17449532
TI  - Febrile neutropenia: transition towards a risk-directed approach.

PMID- 17449533
TI  - The edge: living and working on the Thai-Burmese border.

PMID- 17449534
TI  - Cranial ultrasound as a non-invasive diagnostic technique in the diagnosis of
      subdural haemorrhage.

PMID- 17449535
TI  - The application of telemedicine to geriatric medicine.
AB  - BACKGROUND: Telemedicine has the potential to improve access to the specialty of
      geriatric medicine, particularly in rural and remote settings. While telemedicine
      is widely used in some specialities, this is not yet the case in geriatric
      medicine. OBJECTIVE: To review the current literature to identify proven and
      potential strategies for application of telemedicine in geriatric medical
      practice. METHOD: A comprehensive review of literature pertaining to the
      application of telemedicine in geriatric medicine and relevant related sub
      specialties was undertaken. RESULTS: A large number of small studies of limited
      quality, and a small number of robust studies including randomised trials, were
      identified. CONCLUSIONS: There is evidence to suggest that a variety of
      telemedicine techniques can be applied effectively and safely in geriatric
      medicine across a variety of clinical settings. Patient satisfaction is generally
      reported as high. However, caution is advised due to the paucity of robust
      studies in the literature.

PMID- 17449536
TI  - Evidence of in vitro differential secretion of 72 and 92 kDa type IV collagenases
      after selective exposure to lipopolysaccharide in human fetal membranes.
AB  - Premature rupture of chorioamniotic membranes complicated with intrauterine
      infection has been associated to degradation of extracellular matrix (ECM), which
      could explain local morphological changes. We used a culture system in which the
      chorioamniotic membranes form two independent chambers, allowing for the
      selective stimulation of either the amnion (AMN) and/or the choriodecidua (CHD)
      regions. Lipopolysaccharide (500 ng/ml) was added to the AMN and/or the CHD;
      secretions and gelatinolytic activity of matrix metalloproteinase (MMP)-2 and MMP
      9 were measured in both compartments by enzyme-linked immunosorbent assay (ELISA)
      and zymography. Secretions of TIMP-1, TIMP-2 and TIMP-4 were measured by ELISA.
      Both metalloproteinases were immunolocalized in tissue sections. All stimulation
      modalities induced a similar proMMP-2 and proMMP-9 secretion pattern in the CHD
      with concentrations of 2.49 ng/ml and 90.91 pg/ml, respectively; the AMN showed
      no significant changes. The active forms of both enzymes did not change with any
      stimulation modality. TIMP-1, TIMP-2 and TIMP-4 secretions remained without
      significant changes (P = 0.41). ECM degradation and structural disarrangement
      were evident after stimulation. Secretion of proMMP-2 and proMMP-9 mainly in the
      CHD, presence of active forms associated to the tissue and minor changes in TIMPs
      secretion could favor ECM degradation and explain the weakening and thinning
      associated with the pathological rupture of chorioamniotic membranes.

PMID- 17449537
TI  - Pregnancy-associated CA125 antigen as mucin: evaluation of ferning morphology.
AB  - CA125 antigen is a high molecular mass, structurally heterogeneous, mucin-type
      molecule expressed during embryonic development as well as in adult human
      tissues. This study was aimed at investigating its mucin-related property of
      ferning, as a general complementary way of characterization. Pregnancy-associated
      CA125 antigen (pCA125) was examined using light, transmission and scanning
      electron microscopy and compared with cancer-derived CA125 antigen (cCA125). The
      results obtained for spread-out, air-dried pCA125 and cCA125 samples revealed
      clear differences in the patterns of crystalline as well as amorphous material.
      Thus, the fern-like crystals were mainly sparsely distributed and their
      morphology was atypical. The extent of crystallization of pCA125 was moderately
      lower than that of cCA125 antigen, whereas variation in the size and spatial
      organization of fern crystals was evident. Besides the material with a
      crystalline appearance, differences in the organic substrate were also
      noticeable. In contrast to the sponge-like appearance of pCA125, cCA125 had a
      more compact structure. These initial data may be relevant for relating
      biochemical properties of CA125 antigen with its morphology as a basis for
      elucidating its still obscure function under different physiological conditions.

PMID- 17449538
TI  - Inhibition of progesterone production in human luteinized granulosa cells treated
      with LXR agonists.
AB  - Progesterone production by luteal cells is dependent on the supply of cholesterol
      by lipoproteins. The aim of this study was to determine whether the liver X
      receptors (LXRs) contribute to cholesterol homeostasis and progesterone secretion
      in human luteinized granulosa cells. Cells were isolated from follicular
      aspirates of patients undergoing in vitro fertilization. Luteinization was
      induced by a 7-day treatment with human chorionic gonadotrophin. LXR beta was
      expressed at higher levels than LXR alpha in granulosa cells and its expression
      was increased during luteinization. Treatment of luteinized granulosa cells by
      LXR agonists induced a significant time- and dose-dependent reduction in
      progesterone secretion (50% reductions after a 7-day treatment with 1-microM of
      either GW3965 or T0901317). mRNA levels of steroidogenic genes including
      steroidogenic acute regulatory protein and P450 side-chain cleavage were only
      moderately affected by LXR activation, with a significant reduction that was
      observed at 10 microM agonist concentration. Cellular cholesterol was markedly
      reduced after treatment with LXR agonists as a result of an increased cholesterol
      efflux that was related to the induction of LXR target genes (ABCA1, ABCG1, apo
      E, PLTP). Our study identifies LXRs as new, key actors contributing to regulation
      of cholesterol metabolism and steroidogenesis in luteinized granulosa cells.

PMID- 17449539
TI  - Interaction between cytochrome P450 gene polymorphisms and serum organochlorine
      TEQ levels in the risk of endometriosis.
AB  - Exposure to dioxins and polychlorinated biphenyls (PCBs) has been suggested as a
      possible etiologic factor for endometriosis, but the association remains highly
      controversial. To assess whether cytochrome P450 (CYP) gene polymorphisms
      modulate the effect of dioxins and/or PCBs in endometriosis risk, we conducted a
      case-control study among infertile Japanese women. A total of 138 eligible women
      aged 20-45 were diagnosed laparoscopically and classified into three subgroups:
      control (no endometriosis), early endometriosis (stages I-II) and advanced
      endometriosis (stages III-IV). Neither CYP1A1 Ile462Val and CYP1B1 Leu432Val
      polymorphisms (genotypes with versus genotypes without the minor allele) nor
      serum dioxin and PCB toxic equivalency (TEQ) levels (low versus high) were
      independently associated with either early or advanced endometriosis risk.
      However, genotypes with the CYP1A1 462Val allele showed a statistically
      significant reduced risk of advanced endometriosis in combination with high serum
      dioxin TEQ levels (adjusted odds ratio = 0.13, 95% confidence interval: 0.02
      0.76) (P for interaction = 0.08). Although no association was found between serum
      PCB TEQ level and advanced endometriosis in any stratum of CYP1B1 Leu432Val
      polymorphism, a statistically significant interaction was found (P for
      interaction = 0.05). CYP1A1 and CYP1B1 polymorphisms may modify the relation
      between environmental exposure to organochlorine and advanced endometriosis risk.

PMID- 17449540
TI  - Relationship between muscular effort and generalized central fatigue following
      marathon running in man.

PMID- 17449541
TI  - Can human cardiovascular regulation during exercise be learnt from feedback from
      arterial baroreceptors?
AB  - During dynamic exercise, a large fall in systemic vascular resistance occurs.
      Arterial pressure (AP) is, however, maintained through a combination of central
      command and neural activity from muscle afferents that adjust the autonomic
      outflow to the circulation. How these signals are calibrated to provide accurate
      regulation of AP remains unclear. This study tests the hypothesis that the
      calibration can be 'learnt' through feedback from the arterial baroreceptors
      arising over multiple trials of exercise. Eight healthy subjects undertook three
      different protocols in random order. The test protocol consisted of 7 days'
      training, when subjects were exposed on 70 occasions to 4 min of exercise (50% of
      maximal oxygen uptake capacity) paired with neck suction (-40 mmHg) to mimic an
      excessive rise in AP at the carotid baroreceptors with exercise. Two control
      protocols involved training with either exercise or neck suction alone. No
      significant changes in mean AP, diastolic AP or heart rate during normal exercise
      were detected following training with any protocol. However, the rise in systolic
      AP with exercise was attenuated by an average of 7.3 +/- 2.0 mmHg (mean +/-
      s.e.m., P < 0.01) on the first and second days following training with the test
      protocol, but not with either control protocol (P < 0.05 for difference between
      protocols, ANOVA). In conclusion, this study failed to show that mean AP during
      normal exercise could be reduced through prior conditioning by overstimulation of
      the baroreceptors during exercise. However, a reduction in systolic AP was
      observed that suggests the presence of some plasticity within the autonomic
      response, consistent with our hypothesis.

PMID- 17449542
TI  - Control of microvascular oxygen pressures during recovery in rat fast-twitch
      muscle of differing oxidative capacity.
AB  - Whether the speed of recovery of microvascular O(2) pressures (Pmvo(2) ) differs
      within muscles composed primarily of type II fibres with contrasting oxidative
      capacity has not been determined. We tested the hypothesis that, following
      contractions, the recovery of Pmvo(2) would be slower in the white (WG; low
      oxidative capacity) versus the mixed gastrocnemius (MG; comparatively high
      oxidative capacity). Radiolabelled microsphere and phosphorescence quenching
      techniques were used to measure muscle blood flow ( Q, hence O(2) delivery,
      Q(O2)) and during contractions (1 Hz twitch) at low (LO, 2.5 V) and high
      intensities (HI, 4.5 V) in rat (n = 15) MG and WG muscle and during subsequent
      recovery. Following the LO protocol, end-contraction Pmvo(2) was lower in WG
      (11.6 +/- 0.5 mmHg) than in MG (16.2 +/- 0.6 mmHg; P < 0.05) while, contrary to
      our hypothesis, the initial rate of change in during recovery ( d P(O2)/dt; MG
      0.11 +/- 0.01 mmHg s(-1) and WG 0.06 +/- 0.03 mmHg s(-1)) and mean response time
      (MRT; MG 110.3 +/- 5.1 s and WG 113.5 +/- 8.4 s, P > 0.05) were not different. In
      contrast, end-contraction baseline Pmvo(2) was not different following the HI
      protocol (MG 10.3 +/- 0.6 mmHg and WG 9.2 +/- 0.6 mmHg; P > 0.05) but, in
      agreement with our hypothesis, d P(O2)/dt was slower (MG 0.07 +/- 0.01 mmHg s(-1)
      and WG 0.03 +/- 0.003 mmHg s(-1); P < 0.05) and MRT longer (WG 180.8 +/- 4.5 s
      and MG 115.4 +/- 6.7 s; P < 0.05) in WG versus MG following the HI protocol.
      These data suggest that following high-intensity, though submaximal, muscle
      contractions, Pmvo(2) recovers much faster in the more oxidative mixed
      gastrocnemius than in the less oxidative white gastrocnemius.

PMID- 17449543
TI  - Voxel based analyses of diffusion tensor imaging in Fabry disease.
AB  - BACKGROUND: Fabry disease (FD) is a lysosomal storage disorder associated with
      marked cerebrovascular disease. Conventional MRI shows an extensive load of white
      matter lesions (WMLs) which may already be present at an early stage in the
      disease. OBJECTIVE: Investigator independent and sensitive quantification of
      structural changes in the brain in clinically affected men and women with FD.
      METHODS: We performed a voxel based analysis of diffusion tensor images (DTI) in
      25 patients with FD and 20 age matched normal controls. RESULTS: DTI revealed
      significant increases in cerebral white matter mean diffusivity (MD) in patients
      with FD, which were pronounced in the periventricular white matter. Even the
      subgroup of patients without significant WMLs load (n = 18) showed increased
      diffusivity in the cerebral white matter. In gray matter areas, MD elevation was
      detected only in the posterior part of the thalamus, independent of the visible
      pulvinar alterations on T1 weighted images. Voxel based fractional anisotropy
      measurements did not differ significantly between patients and controls.
      CONCLUSIONS: The present study demonstrates the clinical feasibility of voxel
      based analysis of DTI as a sensitive tool to quantify brain tissue alterations in
      FD. The pattern of increased brain tissue diffusivity is probably due to
      microangiopathic alterations, mainly affecting the long perforating arteries.

PMID- 17449544
TI  - Towards an integrative approach to the management of myotonic dystrophy type 1.

PMID- 17449545
TI  - Possible usefulness of apocynin, an NADPH oxidase inhibitor, for nitrate
      tolerance: prevention of NO donor-induced endothelial cell abnormalities.
AB  - The long-term benefits of nitroglycerin therapy are limited by tolerance
      development. Understanding the precise nature of mechanisms underlying
      nitroglycerin-induced endothelial cell dysfunction may provide new strategies to
      prevent tolerance development. In this line, we tested interventions to prevent
      endothelial dysfunction in the setting of nitrate tolerance. When bovine aortic
      endothelial cells (BAECs) were continuously treated with nitric oxide (NO)
      donors, including nitroglycerin, over 2-3 days, basal production of nitrite and
      nitrate (NO(x)) was diminished. The diminished basal NO(x) levels were mitigated
      by intermittent treatment allowing an 8-h daily nitrate-free interval during the
      2- to 3-day treatment period. Addition of the nicotinamide adenine dinucleotide
      phosphate (NADPH) oxidase inhibitor apocynin restored the basal levels of NO(x)
      that were decreased by continuous nitroglycerin treatment of BAECs. Apocynin
      caused significant improvement of increased mRNA and protein levels of
      endothelial nitric oxide synthase (eNOS) in BAECs given nitroglycerin
      continuously over the treatment period. Apocynin also reduced endothelial
      production of reactive oxygen species (ROS) after continuous nitroglycerin
      treatment. These results showed an essential similarity to the effects of a
      nitrate-free interval. Application of the NOS inhibitor N(omega)-nitro- l
      arginine methyl ester caused a recovery effect on basal NO(x) and eNOS expression
      but was without effect on ROS levels in continuously NO donor-treated BAECs. In
      conclusion, the present study characterized abnormal features and functions of
      endothelial cells following continuous NO donor application. We suggest that
      inhibition of NADPH oxidase, by preventing NO donor-induced endothelial
      dysfunction, may represent a potential therapeutic strategy that confers
      protection from nitrate tolerance development.

PMID- 17449546
TI  - Influence of age on cardiac baroreflex function during dynamic exercise in
      humans.
AB  - We investigated the influence of aging on cardiac baroreflex function during
      dynamic exercise in seven young (22 +/- 1 yr) and eight older middle-aged (59 +/-
      2 yr) healthy subjects. Carotid-cardiac baroreflex function was assessed at rest
      and during moderate-intensity steady-state cycling performed at 50% heart rate
      reserve (HRR). Five-second pulses of neck pressure and neck suction from +40 to 
      80 Torr were applied to determine the operating point gain (G(OP)) and maximal
      gain (G(MAX)) of the full carotid-cardiac baroreflex function curve and examine
      baroreflex resetting during exercise. At rest, mean arterial pressure (MAP) and
      heart rate were similar between the younger and older subjects. In contrast, the
      resting G(OP) and G(MAX) were significantly lower in the older subjects. The
      increase in MAP from rest to exercise was greater in the older subjects (Delta
      +20 +/- 2 older vs. Delta +6 +/- 3 younger mmHg; P < 0.001). However, the G(OP)
      was similar in both groups during exercise because of a reduction in the younger
      subjects. In contrast, G(MAX) was unchanged from rest and therefore remained
      lower in older subjects (-0.19 +/- 0.05 older vs. -0.42 +/- 0.05 younger
      beats.min(-1).mmHg(-1); 50% HRR; P < 0.001). Furthermore, exercise resulted in an
      upward and rightward resetting of the cardiac baroreflex function curve in both
      groups. Collectively, these findings suggest that the cardiac baroreflex function
      curve appropriately resets during exercise in older subjects but operates at a
      reduced G(MAX) primarily because of age-related reductions in carotid-cardiac
      control manifest at rest.

PMID- 17449547
TI  - Asynchrony of ventricular activation affects magnitude and timing of fiber
      stretch in late-activated regions of the canine heart.
AB  - Abnormal electrical activation of the left ventricle results in mechanical
      dyssynchrony, which is in part characterized by early stretch of late-activated
      myofibers. To describe the pattern of deformation during "prestretch" and gain
      insight into its causes and sequelae, we implanted midwall and transmural arrays
      of radiopaque markers into the left ventricular anterolateral wall of open-chest,
      isoflurane-anesthetized, adult mongrel dogs. Biplane cineradiography (125 Hz) was
      used to determine the time course of two- and three-dimensional strains while
      pacing from a remote, posterior wall site. Strain maps were generated as a
      function of time. Electrical activation was assessed with bipolar electrodes.
      Posterior wall pacing generated prestretch at the measurement site, which peaked
      44 ms after local electrical activation. Overall magnitudes and transmural
      gradients of strain were reduced when compared with passive inflation. Fiber
      stretch was larger at aortic valve opening compared with end diastole (P < 0.05).
      Fiber stretch at aortic valve opening was weakly but significantly correlated
      with local activation time (r(2) = 0.319, P < 0.001). With a short
      atrioventricular delay, fiber lengths were not significantly different at the
      time of aortic valve opening during ventricular pacing compared with atrial
      pacing. However, ejection strain did significantly increase (P < 0.05). We
      conclude that the majority of fiber stretch occurs after local electrical
      activation and mitral valve closure and is different from passive inflation. The
      increased shortening of these regions appears to be because of a reduced
      afterload rather than an effect of length-dependent activation in this
      preparation.

PMID- 17449548
TI  - High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous
      to MTHFR C677T mutation is associated with endothelial dysfunction and
      homocysteinemia.
AB  - The aim of this study was to examine the association of homozygosity for the
      methylenetetrahydrofolate reductase (MTHFR) C677T mutation and vitamin B12
      deficiency in 360 asymptomatic individuals and to investigate forearm endothelial
      function in C677T homozygotes. MTHFR C677T mutation and levels of vitamin B12,
      folic acid, and homocysteine were measured in study participants. Frequency of
      homozygosity for the C677T mutation was 67/360 (18.6%). Homocysteine levels were
      elevated in homozygous compared with heterozygous subjects or those without the
      mutation (20.6 +/- 18.8 vs. 9.4 +/- 3.2 mumol/l; P < 0.0001). The number of
      subjects with vitamin B12 deficiency (<150 pmol/l) was significantly higher among
      the homozygote than the heterozygote subjects or subjects without mutation [20/67
      (29.8%) vs. 27/293 (9.2%); P < 0.0001]. Homozygote subjects had 4.2 times higher
      probability of having B12 deficiency (95% confidence interval = 2.1-8.3). Forearm
      endothelial function was assessed in 33 homozygote and 12 control subjects.
      Abnormal endothelial function was observed in homozygous subjects and was worse
      in homozygote subjects with vitamin B12 deficiency. Endothelial function was
      normalized after B12 and folic acid treatment. We found that homozygosity for the
      C677T mutation is strongly associated with B12 deficiency. Coexistence of
      homozygosity for the C677T mutation and B12 deficiency is associated with
      endothelial dysfunction and can be corrected with vitamin B12 and folic acid
      treatment.

PMID- 17449549
TI  - Analysis of complex flow and the relationship between blood pressure, wall shear
      stress, and intima-media thickness in the human carotid artery.
AB  - BACKGROUND: Previous clinical studies have observed relationships between
      increased intima-media thickness (IMT) in the carotid artery, elevated blood
      pressure, and low wall shear stress (WSS) calculated from the Poiseuille
      equation. This study used numerical methods to more accurately determine WSS in
      the carotid artery and to investigate possible determinants of increased IMT.
      METHODS: IMT [common carotid artery (CCA) and bulb], CCA flow velocity, brachial
      systolic (SBP) and diastolic blood pressure (DBP), and carotid systolic pressure
      (cSBP) were measured in 14 healthy subjects (aged 44 +/- 16 yr). Flow patterns in
      the carotid bifurcation were determined by computational fluid dynamics (CFD)
      based on three-dimensional ultrasound geometry. Instantaneous and time-averaged
      wall shear stress (WSS(av)), oscillatory shear index (OSI), and wall shear stress
      angle gradients (WSSAG) were calculated. RESULTS: IMT was positively related to
      SBP, DBP, cSBP, and WSSAG and inversely related to WSS(av) in the CCA. In the
      bulb, IMT was positively related to SBP and cSBP but was not significantly
      related to WSS(av) or WSSAG. IMT was unrelated to OSI in both the CCA and the
      bulb. CONCLUSION: Increased carotid artery IMT in healthy subjects with no
      evidence of focal plaques is primarily a response to elevated pressure.

PMID- 17449550
TI  - 17beta-estradiol deficiency reduces potassium excretion in an angiotensin type 1
      receptor-dependent manner.
AB  - This study examined the effects of ovariectomy (OVX) and 17beta-estradiol (E(2))
      replacement (OVX + E(2)) on renal function in Sprague-Dawley rats. OVX caused a
      40% decrease in the fractional excretion of potassium (FE(K(+))) that was
      prevented by E(2) replacement [Sham, 24.2 +/- 2.9%; OVX, 14.5 +/- 2.1% (P < 0.05
      vs. OVX + E(2)); and OVX + E(2), 26.2 +/- 2.7%; n = 7-11] and that corresponded
      to significant increases in plasma potassium [(in mmol/l): Sham, 3.15 +/- 0.087;
      OVX, 3.42 +/- 0.048 (P < 0.05 vs. OVX + E(2)); and OVX + E(2), 3.19 +/- 0.11; n =
      7-11]. No effects of OVX were detected on plasma levels of sodium and
      aldosterone. Angiotensin II type 1 receptor (AT(1)R) densities in ovariectomized
      rats were 1.4-fold and 1.3-fold higher in glomerular [maximum binding capacity
      (B(max); in fmol/mg protein): Sham, 482 +/- 21; OVX, 666 +/- 20 (P < 0.05 vs. OVX
      + E(2)); and OVX + E(2), 504 +/- 26; n = 7-11] and proximal tubular [B(max) (in
      fmol/mg protein): Sham, 721 +/- 16; OVX, 741 +/- 24 (P < 0.05 vs. OVX + E(2));
      and OVX + E(2), 569 +/- 23; n = 7-11] membranes compared with E(2) replete
      animals, respectively. Both the angiotensin-converting enzyme inhibitor captopril
      and the AT(1)R antagonist losartan prevented the OVX-induced decrease in the
      FE(K(+)) and the increase in renal AT(1)R densities, suggesting that E(2)
      deficiency reduces potassium excretion in an ANG II/AT(1)R-dependent manner.
      These findings may have implications for renal function in postmenopausal women
      as well as contribute to the reasons underlying the age-induced increase in
      susceptibility to hypertension-associated disease in women.

PMID- 17449551
TI  - Subcellular targeting of phosphatases: a novel function of ankyrins.

PMID- 17449552
TI  - Can we use surrogate vascular beds for evaluating endothelial function of the
      coronary vasculature in patients with cardiac allografts?

PMID- 17449553
TI  - Interstitial norepinephrine concentrations in skeletal muscle of ischemic heart
      failure.
AB  - During exercise, sympathetic nerve responses are accentuated in heart failure
      (HF), and this enhances norepinephrine (NE) release and evokes vasoconstriction.
      Two key pathophysiological responses could contribute to the greater NE release:
      1) increased sympathetic nerve discharge and 2) increased NE in the neurovascular
      junction for a given level of sympathetic discharge. In this report, we focus on
      the second of these two general issues and test the following hypotheses: 1) in
      HF for a given level of sympathetic nerve stimulation, NE concentration in the
      interstitium (an index of neurovascular NE) would be greater, and 2) the greater
      interstitial NE concentration would be linked to reduced NE uptake. Studies were
      performed in rats 8-10 wk after induction of myocardial infarction (MI).
      Interstitial NE samples were collected from microdialysis probes inserted into
      the hindlimb muscle. Dialysate concentration of NE was determined by the HPLC
      method. First, interstitial NE concentration increased during electrical
      stimulation of the lumbar sympathetic nerves in eight control rats. An increase
      in interstitial NE concentration was significantly greater in 10 rats with severe
      MI. Additionally, an NE uptake-1 inhibitor (desipramine, 1 microM) was injected
      into the arterial blood supply of the muscle in six control and eight MI rats.
      Desipramine increased interstitial NE concentration by 24% in control and by only
      3% (P < 0.05 vs. control) in MI rats. In conclusion, given levels of electrical
      stimulation of the lumbar sympathetic nerve lead to higher interstitial NE
      concentration in HF. This effect is due, in part, to reduced NE uptake-1 in HF.

PMID- 17449554
TI  - Speckle-tracking strain echocardiography for detecting cardiac dyssynchrony in a
      canine model of dyssynchrony and heart failure.
AB  - Multiple echocardiographic criteria have been proposed to diagnose mechanical
      dyssynchrony in patients with heart failure without being validated against a
      model of cardiac dyssynchrony with heart failure. This study examines which of
      these methods can detect dyssynchrony in a canine model. Adult mongrel dogs
      underwent His-bundle ablation and right-ventricular pacing for 4 wk at either 110
      bpm to induce dyssynchrony without heart failure (D group, n = 12) or 170 bpm to
      induce dyssynchrony with heart failure (DHF group, n = 9). To induce heart
      failure with narrow QRS, atria were paced at 190 bpm for 4 wk (HF group, n = 8).
      Tissue Doppler imaging (TDI) and two-dimensional echocardiography were performed
      at baseline and at end of study. Standard deviation of time to peak systolic
      velocity (color-coded TDI), time to peak S wave on pulse-wave TDI, time to peak
      radial and circumferential strain by speckle-tracking analysis (E(rr) and E(cc),
      respectively), and septal-to-posterior wall motion delay on M mode were obtained.
      In D group, only E(rr) and E(cc) were increased by dyssynchrony. In contrast, all
      the echocardiographic parameters of dyssynchrony appeared significantly augmented
      in the DHF group. Receiver-operator curve analysis showed good sensitivity of
      E(rr) (90%) and E(cc) (100%) to detected dyssynchrony without heart failure and
      excellent sensitivity and specificity of E(rr) and E(cc) to detect dyssynchrony
      with heart failure. Radial strain by speckle tracking is more accurate than TDI
      velocity to detect cardiac dyssynchrony in a canine model of dyssynchrony with or
      without heart failure.

PMID- 17449555
TI  - Effects of erythrocyte flexibility on microvascular perfusion and oxygenation
      during acute anemia.
AB  - Responses to exchange transfusion using red blood cells (RBCs) with normal and
      reduced flexibility were studied in the hamster window chamber model during acute
      moderate isovolemic hemodilution to determine the role of RBC membrane stiffness
      in microvascular perfusion and tissue oxygenation. Erythrocyte stiffness was
      increased by 30-min incubation in 0.02% glutaraldehyde solution, and unreacted
      glutaraldehyde was completely removed. Filtration pressure through 5-microm pore
      size filters was used to quantify stiffness of the RBCs. Anemic conditions were
      induced by two isovolemic hemodilution steps using 6% 70-kDa dextran to a
      hematocrit (Hct) of 18% (moderate hemodilution). The protocol continued with an
      exchange transfusion to reduce native RBCs to 75% of baseline (11% Hct) with
      either fresh RBCs (RBC group) or reduced-flexibility RBCs (GRBC group) suspended
      in 5% albumin at 18% Hct; a plasma expander (6% 70-kDa dextran; Dex70 group) was
      used as control. Systemic parameters, microvascular perfusion, capillary
      perfusion [functional capillary density (FCD)], and oxygen levels across the
      microvascular network were measured by noninvasive methods. RBC deformability for
      GRBCs was significantly decreased compared with RBCs and moderate hemodilution
      conditions. The GRBC group had a greater mean arterial blood pressure (MAP) than
      the RBC and Dex70 groups. FCD was substantially higher for RBC (0.81 +/- 0.07 of
      baseline) vs. GRBC (0.32 +/- 0.10 of baseline) and Dex70 (0.38 +/- 0.10 of
      baseline) groups. Microvascular tissue Po(2) was significantly lower for Dex70
      and GRBC vs. RBC groups and the moderate hemodilution condition. Results were
      attributed to decreased oxygen uploading in the lungs and obstruction of tissue
      capillaries by rigidified RBCs, indicating that the effects impairing RBC
      flexibility are magnified at the microvascular level, where perfusion and
      oxygenation may define transfusion outcome.

PMID- 17449556
TI  - Genetic and dietary interactions: role of angiotensin AT1a receptors in response
      to a high-fructose diet.
AB  - The renin-angiotensin system (RAS) has been implicated in the cardiovascular
      complications of diabetes. We showed that a high-fructose diet increases blood
      pressure and plasma angiotensin and impairs glucose tolerance. We investigated
      the role of angiotensin AT(1a) receptors in the development of fructose-induced
      cardiovascular and metabolic dysfunction. Male angiotensin AT(1a) knockout
      (AT1aKO) and wild-type (AT1aWT) mice with arterial telemetric catheters were fed
      a standard diet or one containing 60% fructose. Fructose increased mean arterial
      pressure (MAP) in AT1aWT but only during the dark phase (8% increase). In AT1aKO
      mice, fructose unexpectedly decreased MAP, during both light and dark periods (24
      and 13% decrease, respectively). Analytical methods were used to measure systolic
      arterial pressure (SAP) and pulse interval (PI) variability in time and frequency
      domains. In fructose-fed AT1aWT mice, there was an increase in SAP variance and
      its low-frequency (LF) domain (11 +/- 3 vs. 23 +/- 4 mmHg(2), variance, and 7 +/-
      2 vs. 17 +/- 3 mmHg(2), LF, control vs. fructose, P < 0.004). There were no
      changes in SAP variance in AT1aKO mice. Depressor responses to alpha(1)
      adrenergic blockade were augmented in fructose-fed AT1a WT compared with AT1aKO
      mice. Fructose inhibited glucose tolerance with a greater effect in AT1aWT mice.
      Fructose increased plasma cholesterol in both groups (P < 0.01) and reduced ANG
      II in AT1aKO mice. Results document prominent interactions between genetics and
      diet with data showing that in the absence of angiotensin AT(1a) receptors, a
      fructose diet decreased blood pressure.

PMID- 17449557
TI  - Diaphragm single-fiber weakness and loss of myosin in congestive heart failure
      rats.
AB  - Diaphragm weakness commonly occurs in patients with congestive heart failure
      (CHF) and is an independent predictor of mortality. However, the pathophysiology
      of diaphragm weakness is poorly understood. We hypothesized that CHF induces
      diaphragm weakness at the single-fiber level by decreasing myosin content. In
      addition, we hypothesized that myofibrillar Ca(2+) sensitivity is decreased and
      cross-bridge kinetics are slower in CHF diaphragm fibers. Finally, we
      hypothesized that loss of myosin in CHF diaphragm weakness is associated with
      increased proteolytic activities of caspase-3 and the proteasome. In skinned
      diaphragm single fibers of rats with CHF, induced by left coronary artery
      ligation, maximum force generation was reduced by approximately 35% (P < 0.01)
      compared with sham-operated animals for slow, 2a, and 2x fibers. In these CHF
      diaphragm fibers, myosin heavy chain content per half-sarcomere was concomitantly
      decreased (P < 0.01). Ca(2+) sensitivity of force generation and the rate
      constant of tension redevelopment were significantly reduced in CHF diaphragm
      fibers compared with sham-operated animals for all fiber types. The cleavage
      activity of the proteolytic enzyme caspase-3 and the proteasome were
      approximately 30% (P < 0.05) and approximately 60% (P < 0.05) higher,
      respectively, in diaphragm homogenates from CHF rats than from sham-operated
      rats. The present study demonstrates diaphragm weakness at the single-fiber level
      in a myocardial infarct model of CHF. The reduced maximal force generation can be
      explained by a loss of myosin content in all fiber types and is associated with
      activation of caspase-3 and the proteasome. Furthermore, CHF decreases
      myofibrillar Ca(2+) sensitivity and slows cross-bridge cycling kinetics in
      diaphragm fibers.

PMID- 17449558
TI  - Arrhythmia susceptibility and premature death in transgenic mice overexpressing
      both SUR1 and Kir6.2[DeltaN30,K185Q] in the heart.
AB  - Sarcolemmal ATP-sensitive potassium (K(ATP)) channels are activated after
      pathological depletion of intracellular ATP, unlike their pancreatic beta-cell
      counterparts, which dynamically regulate membrane excitability in response to
      changes in blood glucose. We recently engineered a series of transgenic (TG) mice
      overexpressing an ATP-insensitive inward rectifying K(+) channel protein (Kir)6.2
      mutant (Kir6.2[DeltaN30,K185Q]) or the accessory sulfonylurea receptor (SUR)2A
      (FLAG-SUR2A) or SUR1 (FLAG-SUR1) subunits of the K(ATP) channel, under
      transcriptional control of the alpha-myosin heavy chain promoter. In the present
      study, we generated double transgenic (DTG) animals overexpressing both
      Kir6.2[DeltaN30,K185Q] and FLAG-SUR1 or FLAG-SUR2A and examined the effects on
      cardiac excitability in vivo. No animals expressing both FLAG-SUR1 and
      Kir6.2[DeltaN30,K185Q] transgenes at a high level were obtained. DTG mice
      expressing one transgene at a high level and the other at a lower level are born,
      but they die prematurely. Electrocardiographic analysis of both anesthetized and
      conscious animals revealed a constellation of arrhythmias in DTG animals, but not
      in wild-type or single TG littermates. The proarrhythmic effect of the transgene
      combination is intrinsic to the myocardium, since it persists in isolated hearts.
      Importantly, this effect is specific for SUR1-expressing DTG animals: DTG animals
      expressing both Kir6.2[DeltaN30,K185Q] and FLAG-SUR2A at high levels exhibit
      neither impaired survival nor increased arrhythmia frequency, even with both
      subunits expressed at high levels. In demonstrating the profound arrhythmic
      consequences of K(ATP) channels comprised of SUR1 and Kir6.2[DeltaN30,K185Q] in
      the myocardium specifically, the results highlight the critical differential
      activation of SUR1 versus SUR2A, and indicate that expression of hyperactive
      K(ATP) in the heart is likely to be proarrhythmic.

PMID- 17449559
TI  - Gene-environment interactions in parkinsonism and Parkinson's disease: the
      Geoparkinson study.
AB  - OBJECTIVES: To investigate associations of Parkinson's disease (PD) and
      parkinsonian syndromes with polymorphic genes that influence metabolism of either
      foreign chemical substances or dopamine and to seek evidence of gene-environment
      interaction effects that modify risk. METHODS: A case-control study of 959
      prevalent cases of parkinsonism (767 with PD) and 1989 controls across five
      European centres. Occupational hygienists estimated the average annual intensity
      of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind
      to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A,
      MAO-B, SOD 2, EPHX, DAT1, DRD2 and NAT2 were genotyped. Results were analysed
      using multiple logistic regression adjusting for key confounders. RESULTS: There
      was a modest but significant association between MAO-A polymorphism in males and
      disease risk (G vs T, OR 1.30, 95% CI 1.02 to 1.66, adjusted). The majority of
      gene-environment analyses did not show significant interaction effects. There
      were possible interaction effects between GSTM1 null genotype and solvent
      exposure (which were stronger when limited to PD cases only). CONCLUSIONS: Many
      small studies have reported associations between genetic polymorphisms and PD.
      Fewer have examined gene-environment interactions. This large study was
      sufficiently powered to examine these aspects. GSTM1 null subjects heavily
      exposed to solvents appear to be at increased risk of PD. There was insufficient
      evidence that the other gene-environment combinations investigated modified
      disease risk, suggesting they contribute little to the burden of PD.

PMID- 17449560
TI  - Reducing healthy worker survivor bias by restricting date of hire in a cohort
      study of Vermont granite workers.
AB  - OBJECTIVE: To explore the healthy worker survivor effect (HWSE) in a study of
      Vermont granite workers by distinguishing "prevalent" from "incident" hires based
      on date of hire before or after the start of follow-up. METHODS: Records of
      workers between 1950 and 1982 were obtained from a medical surveillance
      programme. Proportional hazards models were used to model the association between
      silica exposure and lung cancer mortality, with penalised splines used to smooth
      the exposure-response relationship. A sensitivity analysis compared results
      between the original cohort and subcohorts defined by restricting date of hire to
      include varying proportions of prevalent hires. RESULTS: Restricting to incident
      hires reduced the 213 cases by 74% and decreased the exposure range. The maximum
      mortality rate ratio (MRR) was close to twofold in all subcohorts. However, the
      exposure at which the maximum MRR was achieved decreased from 4.0 to 0.6 mg
      year/m3 as the proportion of prevalent hires decreased from 50% in the original
      cohort to 0% in the subcohort of incident hires. CONCLUSION: Despite loss in
      power and restricted exposure range, decreasing the relative proportion of
      prevalent to incident hires reduced HWSE bias, resulting in stronger evidence for
      a dose-response between silica exposure and lung cancer mortality.

PMID- 17449561
TI  - Association between plasma BPDE-Alb adduct concentrations and DNA damage of
      peripheral blood lymphocytes among coke oven workers.
AB  - OBJECTIVES: Coke oven emissions (COE) containing polycyclic aromatic hydrocarbons
      (PAHs) can induce both benzo[a]pyrene-r-7, t-8, t-9,c-10-tetrahydotetrol-albumin
      (BPDE-Alb) adducts and DNA damage. However, the relation between these biomarkers
      for early biological effects is not well documented in coke oven workers.
      METHODS: In this study, the authors recruited 207 male workers exposed to COE and
      102 controls not exposed to COE in the same steel plant in northern China. They
      measured BPDE-Alb adduct concentrations in plasma with reverse-phase high
      performance liquid chromatography and DNA damage in peripheral blood lymphocytes
      with alkaline comet assay. RESULTS: The results showed that the median
      concentration of BPDE-Alb adducts in the exposed group (34.36 fmol/mg albumin)
      was significantly higher than that in the control group (21.90 fmol/mg albumin, p
      = 0.012). The mean Olive tail moment (Olive TM) of DNA damage in the exposed and
      control groups were 1.20 and 0.63, respectively (p = 0.000). Multivariate
      logistic regression analysis revealed that the odds ratio (OR) for BPDE-Alb
      adduct and Olive TM associated with the exposure were 1.72 (95% CI 1.06 to 2.81)
      and 1.96 (95% CI 1.20 to 3.19), respectively. These results show significant
      correlations between the concentrations of BPDE-Alb adduct and Olive TM levels in
      exposed group (r = 0.235, p = 0.001) but not in control group (r = 0.093, p =
      0.353). CONCLUSION: The results suggest that occupational exposure to COE may
      induce both BPDE-Alb adducts and DNA damage in the lymphocytes of coke oven
      workers and that these two markers are useful for monitoring exposure to COE in
      the workplace.

PMID- 17449562
TI  - Projected mesothelioma incidence in men in New South Wales.
AB  - OBJECTIVES: Based on observed numbers of incident mesotheliomas since 1972, to
      predict future numbers in men in New South Wales. METHODS: The incidence of
      mesothelioma was modelled in two ways. First by using an age/birth cohort model,
      and second by using a model based on potential exposure to asbestos in terms of
      age and calendar year. The latter model included a term for clearance of asbestos
      fibres from the lungs, and a term for diagnostic fraction. The age and calendar
      year model was based on the model introduced by Hodgson and colleagues but
      replaced piecewise effects by smooth functions represented by cubic splines.
      RESULTS: The number of mesotheliomas between 2004 and 2060 was predicted as 6690
      with the age-cohort model and as 6779 by the age and calendar year model, with
      peak annual numbers of 187 in the year 2021 and 196 in the year 2014 with the two
      models respectively. CONCLUSIONS: The pattern of parameter estimates in the two
      models was in accord with the known use of amphibole asbestos in Australia. The
      predicted peak year of 2014-21 is 30-35 years after the phasing out of amphibole
      use, and this period is in accord with predictions for the UK and the US; in the
      latter country the peak was 10-15 years earlier corresponding to a marked decline
      of amphibole use in and following the 1960s.

PMID- 17449563
TI  - Follow-up study of chrysotile textile workers: cohort mortality and exposure
      response.
AB  - OBJECTIVES: This report provides an update of the mortality experience of a
      cohort of South Carolina asbestos textile workers. METHODS: A cohort of 3072
      workers exposed to chrysotile in a South Carolina asbestos textile plant (1916
      77) was followed up for mortality through 2001. Standardised mortality ratios
      (SMRs) were computed using US and South Carolina mortality rates. A job exposure
      matrix provided calendar time dependent estimates of chrysotile exposure
      concentrations. Poisson regression models were fitted for lung cancer and
      asbestosis. Covariates considered included sex, race, age, calendar time, birth
      cohort and time since first exposure. Cumulative exposure lags of 5 and 10 years
      were considered by disregarding exposure in the most recent 5 and 10 years,
      respectively. RESULTS: A majority of the cohort was deceased (64%) and 702 of the
      1961 deaths occurred since the previous update. Mortality was elevated based on
      US referent rates for a priori causes of interest including all causes combined
      (SMR 1.33, 95% CI 1.28 to 1.39); all cancers (SMR 1.27, 95% CI 1.16 to 1.39);
      oesophageal cancer (SMR 1.87, 95% CI 1.09 to 2.99); lung cancer (SMR 1.95, 95% CI
      1.68 to 2.24); ischaemic heart disease (SMR 1.20, 95% CI 1.10 to 1.32); and
      pneumoconiosis and other respiratory diseases (SMR 4.81, 95% CI 3.84 to 5.94).
      Mortality remained elevated for these causes when South Carolina referent rates
      were used. Three cases of mesothelioma were observed among cohort members.
      Exposure-response modelling for lung cancer, using a linear relative risk model,
      produced a slope coefficient of 0.0198 (fibre-years/ml) (standard error 0.00496),
      when cumulative exposure was lagged 10 years. Poisson regression modelling
      confirmed significant positive relations between estimated chrysotile exposure
      and lung cancer and asbestosis mortality observed in previous updates of this
      cohort. CONCLUSIONS: This study confirms the findings from previous
      investigations of excess mortality from lung cancer and asbestosis and a strong
      exposure-response relation between estimated exposure to chrysotile and mortality
      from lung cancer and asbestosis.

PMID- 17449564
TI  - Association of blood lead and homocysteine levels among lead exposed subjects in
      Vietnam and Singapore.
AB  - OBJECTIVES: Lead and homocysteine are both linked to cardiovascular disease. With
      this in mind, the authors evaluated the relation between blood lead and
      homocysteine in people aged 19-66 years in two Asian populations. METHODS: This
      cross-sectional study comprised 183 workers from a lead stabiliser factory in
      Singapore and 323 workers from a battery factory in Vietnam. Workers were
      occupationally exposed to lead. Blood lead was analysed using atomic absorption
      spectrophotometry while plasma homocysteine was measured using high performance
      liquid chromatography. RESULTS: Chinese subjects had the lowest blood lead levels
      while the Indians had the highest. Controlling for age, sex and race, an increase
      of 1 microg/dl in blood lead was associated with an increase of 0.04 micromol/l
      of homocysteine on the log scale. Gender and ethnicity seemed to be strongly
      associated with the relation between lead and homocysteine. The positive relation
      between lead and homocysteine among the Vietnamese subjects was significant
      (Pearson's r = 0.254, p<0.01). When blood lead levels were divided by quartiles,
      the correlation coefficient between blood lead levels in the 4th quartile and
      homocysteine among the Vietnamese was higher (r = 0.405, p<0.01). Overall, an
      increase of 1 microg/dl in blood lead in all the Vietnamese subjects was
      associated with an increase of 0.05 micromol/l increase in homocysteine on the
      log scale. However, in the 4th quartile, the same increase was associated with an
      increase of 0.41 micromol/l of homocysteine on the log scale. CONCLUSIONS: Blood
      lead was found to be associated with homocysteine levels in this Asian sample.
      Although we cannot determine causality from cross-sectional data, it is sensible
      to consider the probability that this relation could explain one of the
      mechanisms of the impact of lead on the cardiovascular system. More studies would
      be needed to confirm this inference.

PMID- 17449565
TI  - 3-Hydroxybenzo[a]pyrene in the urine of workers with occupational exposure to
      polycyclic aromatic hydrocarbons in different industries.
AB  - OBJECTIVES: This study was conducted to assess external and internal exposure of
      workers to polycyclic aromatic hydrocarbons (PAHs). In this context, the
      analytical and diagnostical reliability of 3-hydroxybenzo[a]pyrene (3OH-BaP) as a
      biomarker of internal exposure to PAHs was established. METHODS: Ambient and
      biological monitoring was carried out of 225 PAH-exposed employees of different
      industries. External exposure was determined by personal air sampling and
      analysis of 16 EPA-PAH. Internal exposure was examined by the urinary metabolites
      3OH-BaP, 1-hydroxypyrene (OH-Pyr) and monohydroxylated phenanthrenes (OH-Phens).
      RESULTS: Benzo[a]pyrene (BaP) was detected at all workplaces. Concentrations in
      the breathing zone of the workers ranged from below the limit of detection up to
      44.3 mug/m(3). In biological monitoring, urinary 3OH-BaP was found in median
      concentrations of 0.8 ng/g creatinine (crea) and the 95th percentile of 6.7 ng/g
      crea. The results ranged from the limit of detection up to 19.5 ng/g crea. Only
      1% of the analysed samples showed concentrations below the limit of detection
      (0.05 ng/l). Regarding median concentrations, workers in coking plants showed
      lower 3OH-BaP concentrations (0.5 ng/g crea) than those employed in the
      production of fireproof material in refractories (1.1 ng/g crea), converter
      infeed (1.2 ng/g crea) and graphite electrode production (1.3 ng/g crea). Strong
      correlations of 3OH-BaP with OH-Pyr and the sum of OH-Phens were found for the
      workplaces converter infeed, coking plants and graphite electrode production
      (r(Pearson) ranging from 0.618 to 0.867, p<0.001). The poor correlation of BaP in
      the air and 3OH-BaP in urine is most probably caused by routes of uptake other
      than via air-for example, dermal uptake. CONCLUSION: 3OH-BaP as a metabolite of
      the carcinogenic BaP could be shown to be a diagnostically specific and sensitive
      biomarker for determining the internal exposure of workers in different
      industries. Using this method, the estimation of health risks for workers can be
      fundamentally improved, because the 3OH-BaP represents the group of carcinogenic
      PAHs. The procedure for analysing 3OH-BaP is complex, but it is robust and
      produces reliable results.

PMID- 17449566
TI  - Why is the information on cost effectiveness of interventions to manage neck and
      upper limb symptoms still lacking, while all stakeholders would benefit from this
      information?

PMID- 17449567
TI  - Causal relationship between trichloroethylene exposure and non-Hodgkin's
      lymphoma.

PMID- 17449568
TI  - How to undertake a systematic review in an occupational setting.

PMID- 17449569
TI  - Genistein downregulates SREBP-1 regulated gene expression by inhibiting site-1
      protease expression in HepG2 cells.
AB  - Genistein is one of the most abundant isoflavones in soy. The effects of
      genistein on cholesterol synthesis and fatty acid oxidation have been well
      documented, but the effect of genistein on fatty acid synthesis remains unclear.
      Thus, we investigated the effect of genistein on fatty acid synthase (FAS)
      expressions in HepG2 cells. In HepG2 cells treated with 10 micromol/L genistein,
      mRNA and protein expressions of FAS, as well as FAS activity, were significantly
      decreased. The promoter region of FAS contains binding sites for the
      transcription factor called sterol regulated element binding protein 1 (SREBP-1);
      SREBP-1 must be processed by site-1 (S1P) and site-2 proteases to be activated.
      We also investigated the effects of genistein on S1P, SREBP-1 expression, and
      subsequent SREBP-1 processing by S1P in HepG2 cells. Genistein reduced the
      expression of S1P and the processing of SREBP-1 but did not change the expression
      of SREBP-1 mRNA. SREBP-1 is also a transcription factor for lipogenic genes, such
      as stearoyl coenzyme-A desaturase1 (SCD1), glycerol-3-phosphate acyltransferase
      (GPAT), and acetyl-CoA carboxylase (ACC)1, and ACC2. Genistein also significantly
      inhibited the expression of these lipogenic genes. Thus, genistein treatment of
      HepG2 cells decreased the expression of lipogenic genes such as FAS, SCD1, GPAT,
      and ACC, which is, at least in part, mediated through the downregulation of S1P
      expression and subsequent SREBP-1 proteolytic cleavage.

PMID- 17449570
TI  - Dietary selenium affects homocysteine metabolism differently in Fisher-344 rats
      and CD-1 mice.
AB  - In our previous work with rats, plasma and tissue homocysteine concentrations
      were decreased by selenium deprivation. The purpose of this study was to follow
      up and expand on that work by determining the effects of selenium status
      (deficient, adequate, and supranutritional) on several aspects of homocysteine
      metabolism involving methionine recycling and transsulfuration. A 2nd objective
      was to determine whether there are differences in how selenium status affects
      homocysteine metabolism in rats and mice. Male weanling Fischer-344 rats and male
      weanling CD-1 mice were fed diets containing 0, 0.2, or 2.0 microg selenium (as
      sodium selenite)/g for 72 d or 60 d, respectively. Plasma homocysteine and
      cysteine were significantly decreased by feeding rats or mice the selenium
      deficient diet compared with feeding adequate or supranutritional selenium. On
      the other hand, plasma glutathione was increased by selenium deficiency only in
      rats. Also, the specific activities of liver betaine homocysteine
      methyltransferase and glycine N-methyltransferase were decreased by selenium
      deficiency in rats, but were unaffected by selenium status in mice. Real-time RT
      PCR was used to determine the expression of the subunits of glutamate-cysteine
      ligase, which catalyzes the rate-limiting step in glutathione biosynthesis. The
      expression of Gclc, the catalytic subunit of glutamate-cysteine ligase, was
      upregulated by selenium deprivation in both rat and mouse liver. Gclm, the
      modifier subunit of glutamate-cysteine ligase, was downregulated in rats fed 2
      microg Se/g compared with rats fed adequate or deficient selenium. Based on these
      findings, it is evident that selenium deficiency has different outcomes in mice
      and rats. These variables are all related to methionine/methyl metabolism.
      Although only one strain of rat was compared with one strain of mouse, this work
      suggests that differences between species may prove vital in determining which
      animal model is used in studies of selenium deficiency or in studies that are
      designed to ascertain chemopreventive mechanisms of selenium.

PMID- 17449571
TI  - Alkylresorcinols from whole-grain wheat and rye are transported in human plasma
      lipoproteins.
AB  - Alkylresorcinols with alkyl chains C17:0-C25:0 are abundant in whole-grain wheat
      and rye. Concentrations in human plasma have been suggested to be biomarkers of
      dietary whole-grain intake. We measured human plasma, erythrocyte, and
      lipoprotein alkylresorcinol concentrations and alkylresorcinol homolog
      distribution, and evaluated the use of plasma alkylresorcinol concentration as a
      dietary biomarker of whole-grain intake compared with serum enterolactone. A
      total of 15 subjects (8 women) consumed whole-grain wheat or whole-grain rye
      crisp bread ( approximately 100 g/d) in a crossover design for 1 wk. The test
      bread periods were preceded by 1-wk periods of consuming refined wheat bread.
      Plasma, erythrocyte, lipoprotein alkylresorcinol, and serum enterolactone
      concentrations were measured before and after each period, and plasma
      alkylresorcinols and serum enterolactone were measured after habitual diet intake
      before and 1 wk after the trial. Plasma alkylresorcinols are transported in
      lipoproteins with VLDL and HDL being the main carriers. AR concentrations in
      plasma, erythrocytes, and lipoproteins were increased (P < 0.05) by whole-grain
      wheat bread and even more so with rye crisp bread, although interindividual
      variation was high. The alkylresorcinol homolog C17:0 to C21:0 ratio in plasma
      was higher after the whole-grain rye diet period compared with the whole-grain
      wheat diet period (P < 0.05). Serum enterolactone concentrations were increased
      significantly by whole-grain rye intake only in men. This is the first report to
      show that alkylresorcinols in human plasma are mainly transported in
      lipoproteins. The plasma alkylresorcinol C17:0 to C21:0 ratio reflects intake of
      whole-grain wheat and rye, and the plasma total alkylresorcinol concentration
      appears to be a useful biomarker of whole-grain cereal intake.

PMID- 17449572
TI  - Exogenous oxidation of isomaltulose is lower than that of sucrose during exercise
      in men.
AB  - Isomaltulose (ISO) is a disaccharide that is slowly digested, resulting in a slow
      availability for absorption. The aim of this study was to compare the blood
      substrate responses and exogenous carbohydrate (CHO) oxidation rates from orally
      ingested sucrose (SUC) and ISO during moderate intensity exercise. We
      hypothesized that the oxidation of ISO is lower compared with SUC, resulting in
      lower plasma glucose and insulin concentrations and subsequent lower CHO and
      higher fat oxidation rates. Ten trained men [maximal oxygen uptake (VO(2)max), 64
      +/- 1 mL/(kg body mass.min)] cycled on 3 occasions for 150 min at 59 +/- 2%
      VO(2)max and consumed either water (WAT) or 1 of 2 CHO solutions providing 1.1
      g/min of CHO in the form of either SUC or ISO. Peak exogenous CHO oxidation rates
      were higher (P < 0.05) during the SUC trial (0.92 +/- 0.03 g/min) than during the
      ISO trial (0.54 +/- 0.05 g/min). Total endogenous CHO oxidation over the final 90
      min of exercise was lower (P < 0.05) in the SUC trial (107 +/- 10 g) than in the
      WAT (137 +/- 7 g) and ISO (127 +/- 9 g) trials. Fat oxidation was higher during
      the WAT trial than during the SUC and ISO trials. ISO resulted in a lower plasma
      insulin response at 30 min compared with SUC, whereas the glucose response did
      not differ between the 2 CHO. Oxidation of ingested ISO was significantly less
      than that of SUC, most likely due to the lower rate of digestion of ISO. A lower
      CHO delivery and a small difference in plasma insulin may have resulted in higher
      endogenous CHO use and higher fat oxidation during the ISO trial than during the
      SUC trial.

PMID- 17449573
TI  - gamma-Glutamyl hydrolase, not glutamate carboxypeptidase II, hydrolyzes dietary
      folate in rat small intestine.
AB  - Dietary polyglutamyl folates are hydrolyzed to monoglutamyl folate derivatives
      prior to intestinal transport. In humans and pigs, the reaction occurs at pH 6.5
      at the jejunal brush border membrane by folate hydrolase and is encoded by the
      glutamate carboxypeptidase II (GCPII) gene. Intracellular folate hydrolase with
      an optimal pH of 4.5 is encoded by the gamma-glutamyl hydrolase (gamma-GH) gene
      and predominates in rats. We determined the respective roles of GCPII and gamma
      GH in dietary folate hydrolysis in rat small intestine. Duodenal, jejunal, and
      ileal mucosa, pancreas, and duodenal luminal fluid were collected from 10 Sprague
      Dawley rats that had not been food deprived. Folate hydrolase was assayed at pH
      4.5 and 6.5 with and without parahydroxymercuribenzoate (pHMB), an inhibitor of
      intracellular folate hydrolase. Folate hydrolase activity occurred at pH 4.5 in
      all tissues, was significantly inhibited by the addition of pHMB at both pH 4.5
      and 6.5, and was virtually absent from brush border fractions at pH 6.5. The
      highest activity was in the postprandial duodenal luminal fluid at pH 4.5. Rat
      specific primers for GCPII and gamma-GH were used to detect mRNA expression in
      pancreas, jejunal mucosa, and liver. GCPII expression was detected only in the
      liver, whereas gamma-GH was expressed in all 3 tissues. These results suggest
      that the hydrolysis of polyglutamyl folates in rats requires the intracellular
      folate hydrolase that is expressed by pancreatic gamma-GH, in contrast to GCPII
      that is expressed in the jejunal mucosal brush border in pigs and humans. gamma
      GH folate hydrolase is abundant in rat postprandial pancreatic secretions and
      appears to hydrolyze dietary folates in the intestinal lumen prior to intestinal
      absorption.

PMID- 17449574
TI  - Transfer of absorbed cis-9, trans-11 conjugated linoleic acid into milk is
      biologically more efficient than endogenous synthesis from absorbed vaccenic acid
      in lactating cows.
AB  - Cis-9, trans-11, the major isomer of conjugated linoleic acid (CLA) in bovine
      milk fat, is derived from ruminal biohydrogenation of 18:2 (n-6) and endogenous
      conversion of trans-11 18:1 (vaccenic acid; VA) in the mammary gland. Most
      evidence to date suggests that endogenous synthesis is the major source of cis-9,
      trans-11 CLA, but the extent of VA desaturation is less well defined. Four
      lactating cows were used in consecutive 4 x 4 Latin squares to examine changes in
      milk fatty acid composition and secretion in response to abomasal infusions of
      lipid supplements enriched with cis-9, trans-11 CLA (88.8%) or VA (29.4%).
      Treatments were infused over 4-d, followed by a 3-d washout, during 7 d
      experimental periods and administered to deliver 0, 3, 6, and 12 g cis-9, trans
      11 CLA/d (Expt. 1) or 0, 7.5, 15 and 30 g VA/d (Expt. 2). Infusions of cis-9,
      trans-11 CLA increased linearly milk cis-9, trans-11 CLA concentrations from 0.68
      to 1.46 g/100 g fatty acids. Abomasal infusions of VA increased linearly milk VA
      and cis-9, trans-11 CLA content from 1.22 to 2.72 and 0.61 to 1.24 g/100 g fatty
      acids, respectively. Changes in milk fatty acid secretion indicated that 28.9% of
      VA was converted to cis-9, trans-11 CLA. Results provide evidence that conversion
      by Delta9-desaturase to cis-9, trans-11 CLA in the lactating cow is independent
      of postruminal VA supply. In conclusion, endogenous synthesis via VA was
      equivalent to approximately 21% of the response to increases in cis-9, trans-11
      CLA available for absorption.

PMID- 17449575
TI  - Nonheme iron absorption in young women is not influenced by purified sulfated and
      unsulfated glycosaminoglycans.
AB  - Meat is a well-known enhancer of iron absorption, yet the molecular entity
      mediating the effect remains obscure. Recently published data indicate that
      highly acidic sulfated glycosaminoglycans (GAG) from fish and chicken muscle are
      effective stimulants of iron uptake in Caco-2 cells. Two fully randomized stable
      isotope studies with crossover design were performed in a group of 16 apparently
      healthy young women to assess the effect of purified sulfated and unsulfated GAG
      on human iron absorption. Iron absorption was measured on the basis of
      erythrocyte incorporation of (57)Fe or (58)Fe 14 d after the administration of
      labeled semisynthetic meals (SSM) based on egg albumin, corn oil, maltodextrin,
      and water. The meals were consumed with or without added sodium hyaluronate (NaH,
      300 mg) or chondroitin sulfate (CS, 360 mg) as representative unsulfated and
      sulfated GAG, respectively. The level of GAG added was 3 times (NaH) to about 10
      times (CS), the amount expected to be present in 150 g beef muscle. Geometric
      mean iron absorption from SSM containing NaH (21.2%) or CS (19.4%) did not differ
      from that of SSM without GAG (19.5 and 20.3%, respectively). NaH and CS at those
      levels do not affect human nonheme iron absorption.

PMID- 17449576
TI  - A combination of psyllium and plant sterols alters lipoprotein metabolism in
      hypercholesterolemic subjects by modifying the intravascular processing of
      lipoproteins and increasing LDL uptake.
AB  - We previously demonstrated that a diet therapy involving consumption of 7.28 g
      psyllium (PSY) and 2 g of plant sterols (PS) per day reduced LDL cholesterol from
      3.6 +/- 0.7 to 3.1 +/- 0.8 mmol/L (P < 0.01) and decreased the number of
      intermediate density lipoprotein particles and the smaller LDL and HDL
      subfractions in hypercholesterolemic individuals (n = 33). The study design was a
      randomized double blind crossover. Subjects consumed either 2 test cookies
      containing PSY+PS or 2 placebo cookies for 1 mo with a 3-wk wash out between
      treatments. To explore mechanisms of the lipid-lowering effects of combined
      PSY+PS, we present data related to intravascular and molecular regulation. Intake
      of PSY+PS decreased the cholesterol concentration in LDL-1 from 2.46 +/- 0.66 to
      2.26 +/- 0.46 mmol/L and in LDL-2 from 0.63 +/- 0.24 to 0.54 +/- 0.27 mmol/L (P <
      0.05) in the test compared with the placebo period. An increase in LDL peak size
      from 27.3 +/- 0.8 to 27.5 +/- 0.6 nm (P < 0.05) and a decrease in the prevalence
      of LDL pattern B from 27 to 18% (P < 0.05) also occurred during the PSY+PS
      period. Cholesteryl ester transfer protein activity was 11% lower (P < 0.05)
      during the test period. Notably, the abundance of the LDL receptor in circulating
      mononuclear cells as measured by real time PCR was 26% higher during the test
      compared with the placebo period (P < 0.03). These results indicate that the
      hypocholesterolemic action of PSY and PS can be explained in part by
      modifications in the intravascular processing of lipoproteins and by increases in
      LDL receptor-mediated uptake.

PMID- 17449577
TI  - Differences in taurine synthesis rate among dogs relate to differences in their
      maintenance energy requirement.
AB  - Diet-induced (taurine deficiency) dilated cardiomyopathy is reported more in
      large than small dogs possibly because taurine biosynthesis rate (TBR) is lower
      in large than small dogs. The TBR in 6 mongrels (37.9 +/- 2.1 kg) and 6 beagles
      (12.8 +/- 0.4 kg) was determined from the fractional dilution rate of urinary
      [1,2-(2)H(2)]-taurine, (d4-tau). All dogs were given a 15.6% protein, 0.60%
      sulfur amino acid (SAA) diet in amounts to maintain an ideal body condition
      score. After 3 mo, 14.6 mg/kg body weight of d4-tau was given orally and TBR
      determined from d4-tau to taurine ratio in urine collected each d for 6 d.
      Enrichments of d4-tau were determined by GC-MS. Thereafter, mongrels and beagles
      were paired by ranking of SAA intake per metabolic body weight per kg(0.75). Each
      pair received the same amount of diet/kg(0.75) for 2 wk, then TBR was again
      determined. Concentrations of taurine in plasma, blood, and urine and
      concentrations of plasma thiols were measured during each TBR determination. In
      Expt. 1, TBR and taurine concentrations in plasma and urine of mongrels were
      lower (P < 0.05) than those of beagles. In Expt. 2, TBR and taurine
      concentrations in blood and plasma of mongrels were lower (P < 0.05) than
      beagles. Together, the results support the hypothesis that large compared with
      small dogs have lower TBR when fed diets near-limiting in dietary SAA, but
      adequate to maintain ideal body condition.

PMID- 17449578
TI  - Early postnatal iron repletion overcomes lasting effects of gestational iron
      deficiency in rats.
AB  - Iron deficiency anemia in early childhood causes developmental delays and, very
      likely, irreversible alterations in neurological functioning. One primary goal
      for the present study was to determine whether the effects of late gestational
      iron deficiency on brain monoamine metabolism, iron content, and behavioral
      phenotypes could be repaired with iron intervention in early lactation. Young
      pregnant rats were provided iron-deficient or control diets from mid-gestation
      (G15). At postnatal d 4 (P4), pups from iron-deficient dams were out-fostered
      either to other ID dams or control dams while pups of control dams were similarly
      fostered to other control dams. Dietary treatments continued to adulthood (P65)
      when brain iron and regional monoamines were evaluated. P4 iron repletion
      normalized body iron status, brain iron concentrations, monoamine concentrations,
      and monoamine transporter and receptor densities in most brain regions. Dopamine
      transporter densities in caudate and substantia nigra were lower in ID rats but
      were normalized with iron repletion. Serotonin transporter levels in most brain
      regions and open-field exploration were also normalized with iron repletion. The
      success of this approach of early postnatal iron intervention following iron
      deficiency in utero contrasts to a relative lack of success when the intervention
      is performed at weaning. These data suggest that a window of opportunity exists
      for reversing the detrimental effects of iron deficiency in utero in rats and
      provides strong support of intervention approaches in humans with iron deficiency
      during pregnancy.

PMID- 17449579
TI  - Lowering homocysteine with B vitamins has no effect on blood pressure in older
      adults.
AB  - An elevated circulating homocysteine concentration is associated with the risk of
      cardiovascular disease. The mechanism by which an elevated homocysteine increases
      cardiovascular risk is unclear but may be mediated in part by elevating blood
      pressure. It is well established that supplements containing folate, vitamins B
      12, and B-6 lower homocysteine concentrations. However, the effect of
      homocysteine-lowering vitamins on blood pressure has not been well studied. We
      sought to determine whether lowering homocysteine with B vitamins lowers blood
      pressure in healthy older people with elevated homocysteine concentrations. Two
      hundred seventy-six healthy older participants (> or = 65 y) with a homocysteine
      > or = 13 micromol/L were randomized to receive a daily supplement containing
      folate (1 mg), vitamin B-12 (500 microg), and vitamin B-6 (10 mg), or a placebo,
      for 2 y. Plasma homocysteine was lower in the Vitamins group than the Placebo
      group at both 1 [-4.3 micromol/L (95% CI; -4.9, -3.7)] and 2 y [-4.4 micromol/L
      (95% CI: -5.3, -3.6)]. Systolic and diastolic blood pressures as well as pulse
      pressure in the Vitamins group did not differ from the Placebo group over the
      duration of the trial. The mean differences in blood pressures, adjusted for
      baseline values, did not exceed 1 mm Hg. Supplemental B-vitamins lowered plasma
      homocysteine but had no effect on blood pressure in older people with elevated
      baseline homocysteine concentrations.

PMID- 17449580
TI  - Conjugated linoleic acid supplementation for twelve weeks increases lean body
      mass in obese humans.
AB  - Conjugated linoleic acid (CLA) alters body composition in animal models, but few
      studies have examined the effects of CLA supplementation on body composition and
      clinical safety measures in obese humans. In the present study, we performed a
      randomized, double-blind, placebo-controlled trial to examine the changes in body
      composition and clinical laboratory values following CLA (50:50 ratio of cis-9,
      trans-11 and trans-10, cis-12 isomers) supplementation for 12 wk in otherwise
      healthy obese humans. Forty-eight participants (13 males and 35 females) were
      randomized to receive placebo (8 g safflower oil/d), 3.2 g/d CLA, or 6.4 g/d CLA
      for 12 wk. Changes in body fat mass and lean body mass were determined by dual
      energy X-ray absorptiometry. Resting energy expenditure was assessed by indirect
      calorimetry. Clinical laboratory values and adverse-event reporting were used to
      monitor safety. Lean body mass increased by 0.64 kg in the 6.4 g/d CLA group (P <
      0.05) after 12 wk of intervention. Significant decreases in serum HDL-cholesterol
      and sodium, hemoglobin, and hematocrit, and significant increases in serum
      alkaline phosphatase, C-reactive protein, and IL-6, and white blood cells
      occurred in the 6.4 g/d CLA group, although all values remained within normal
      limits. The intervention was well tolerated and no severe adverse events were
      reported, although mild gastrointestinal adverse events were reported in all
      treatment groups. In conclusion, whereas CLA may increase lean body mass in obese
      humans, it may also increase markers of inflammation in the short term.

PMID- 17449581
TI  - Dietary diacylglycerol induces the regression of atherosclerosis in rabbits.
AB  - Recent studies of the relation between serum triacylglycerol concentration and
      the risk for coronary artery disease suggest that inefficient clearance of
      postprandial triacylglycerols promotes atherogenesis. We recently demonstrated
      that dietary diacylglycerol (DAG), rich in the 1,3-species, suppresses the
      postprandial increase in serum triacylglycerol levels compared with dietary
      triacylglycerol (TAG). Here, we investigated the effects of dietary DAG on
      atherosclerosis in rabbits with cholesterol-induced atherosclerosis. New Zealand
      White rabbits (n = 20) were fed a diet containing 3% lard and 1.3% cholesterol
      for 50 d to induce atherosclerotic lesions. Thereafter, the rabbits were assigned
      to 2 groups and fed 90 g/d nonpurified diet and orally administered 5 g DAG or
      TAG for an additional 34 d. Reference rabbits (n = 5) were fed only the
      nonpurified diet throughout the 84-d study. The area of atherosclerotic lesions
      and aortic lipid concentrations were significantly lower in DAG-fed rabbits
      compared with TAG-fed rabbits. The VLDL receptor and macrophage antigen-1 mRNA
      expression levels were significantly lower in DAG-fed rabbits than in TAG-fed
      rabbits. In the liver of DAG-fed rabbits, the triacylglycerol concentration was
      lower and the carnitine palmitoyltransferase activity higher than in TAG-fed
      rabbits. Stimulation of hepatic lipid catabolism might be related to the reduced
      lipid accumulation in the liver and aorta by reducing the release of
      triacylglycerol into the circulation. Thus, long-term consumption of DAG, which
      reduces postprandial lipemia, might be useful for the regression of
      atherosclerosis by stimulating hepatic lipid catabolism and thereby modulating
      monocyte/macrophage migration and aortic lipid accumulation.

PMID- 17449582
TI  - Conjugated linoleic acid induces mast cell recruitment during mouse mammary gland
      stromal remodeling.
AB  - Conjugated linoleic acid (CLA) is a dietary chemopreventive agent that induces
      apoptosis in the mammary adipose vascular endothelium and decreases mammary brown
      adipose tissue (BAT) and white adipose tissue (WAT). To determine onset and
      extent of stromal remodeling, we fed CD2F1/Cr mice diets supplemented with 1 or 2
      g/100 g mixed CLA isomers for 1-7 wk. BAT loss, collagen deposition, and
      leukocyte recruitment occurred in the mouse mammary fat pad, coincident with an
      increase in parenchymal-associated mast cells in mice fed both levels of CLA.
      Feeding experiments with purified isomers (0.5 g/100 g diet) demonstrated that
      these changes were induced by trans-10, cis-12 CLA (10,12-CLA), but not by cis-9,
      trans-11 CLA (9,11-CLA). This stromal remodeling did not require tumor necrosis
      factor (TNF)-alpha, a major cytokine in mast cells, as TNF-alpha null mice
      demonstrated collagen deposition, increased leukocytes, and BAT loss in the
      mammary fat pad in response to 10,12-CLA. To test the hypothesis that mast cells
      recruited in response to 10,12-CLA were required for stromal remodeling, Steel
      mice (WBB6F1/J-kit(W)/kit(W-V)), which lack functional mast cells, were examined
      for their stromal response to 10,12-CLA. Both wild-type and Steel mice showed a
      significantly increased leukocytic adipose infiltrate, collagen deposition, and
      decreased adipocyte size, although BAT was maintained in Steel mice. These
      results demonstrate that 10,12-CLA induces an inflammatory and fibrotic phenotype
      in the mouse mammary gland stroma that is independent of TNF-alpha or mast cells
      and suggest caution in the use of 10,12-CLA for breast cancer chemoprevention.

PMID- 17449583
TI  - Quercetin inhibits TNF-induced NF-kappaB transcription factor recruitment to
      proinflammatory gene promoters in murine intestinal epithelial cells.
AB  - Flavonoids may play an important role for adjunct nutritional therapy of chronic
      intestinal inflammation. In this study, we characterized the molecular mechanisms
      by which quercetin and its enteric bacterial metabolites, taxifolin, alphitonin,
      and 3, 4-dihydroxy-phenylacetic acid, inhibit tumor necrosis factor alpha (TNF)
      induced proinflammatory gene expression in the murine small intestinal epithelial
      cell (IEC) line Mode-K as well as in heterozygous TNFDeltaARE/WT mice, a murine
      model of experimental ileitis. Quercetin inhibited TNF-induced interferon-gamma
      inducible protein 10 (IP-10) and macrophage inflammatory protein 2 (MIP-2) gene
      expression in Mode-K cells with effective inhibitory concentration of 40 and 44
      micromol/L, respectively. Interestingly, taxifolin, alphitonin, and 3,4-dihydroxy
      phenylacetic acid did not inhibit TNF responses in IEC, suggesting that microbial
      transformation of quercetin completely abolished its anti-inflammatory effect. At
      the molecular level, quercetin inhibited Akt phosphorylation but did not inhibit
      TNF-induced RelA/I-kappaB phosphorylation and IkappaB degradation or TNF-alpha
      induced nuclear factor-kappaB transcriptional activity. Most important for
      understanding the mechanism involved, chromatin immunoprecipitation analysis
      revealed inhibitory effects of quercetin on phospho-RelA recruitment to the IP-10
      and MIP-2 gene promoters. In addition, and consistent with the lack of cAMP
      response element binding protein (CBP)/p300 recruitment and
      phosphorylation/acetylation of histone 3 at the promoter binding site, quercetin
      inhibited histone acetyl transferase activity. The oral application of quercetin
      to heterozygous TNFDeltaARE/WT mice [10 mg/(d x kg body wt)] significantly
      inhibited IP-10 and MIP-2 gene expression in primary ileal epithelial cells but
      did not affect tissue pathology. These studies support an anti-inflammatory
      effect of quercetin in epithelial cells through mechanisms that inhibit cofactor
      recruitment at the chromatin of proinflammatory genes.

PMID- 17449584
TI  - Diets rich in polyphenols and vitamin A inhibit the development of type I
      autoimmune diabetes in nonobese diabetic mice.
AB  - Type I juvenile diabetes mellitus is characterized by the infiltration of
      activated T lymphocytes and monocytes into the islets of Langerhans of the
      pancreas, resulting in inflammation and progressive destruction of the insulin
      producing beta cells. We hypothesized that feeding nonobese diabetic (NOD) mice
      diets rich in polyphenols or vitamin A, both known modulators of immune function,
      would decrease the autoimmune inflammatory process associated with type I
      diabetes. NOD mice were fed a control diet (C) and diets containing either 1%
      freeze-dried grape powder (GP) or 250 IU vitamin A/g (VA; 0.262 micromol retinyl
      acetate/g) of food. Mice were considered diabetic and killed when blood glucose
      reached 13.9 mmol/L or greater. By approximately 7 mo of age, 71% of C mice
      progressed to diabetes. Incidence of diabetes was reduced to 33% (P < 0.05) and
      25% (P < 0.05) in mice receiving 1% dietary grape powder and VA, respectively.
      Splenocytes from mice receiving both GP and VA had lower TNF-alpha production
      after LPS stimulation than C mice (P < 0.05). Histological analysis of pancreatic
      tissue showed a significant reduction in the severity of insulitis in the mice
      receiving GP and VA compared with C mice. These data suggest that diets rich in
      polyphenols or vitamin A have protective effects against autoimmune inflammatory
      attack of the islet beta cells and have the potential to reduce the onset and
      pathogenesis of autoimmune diabetes.

PMID- 17449585
TI  - Active hexose correlated compound acts as a prebiotic and is antiinflammatory in
      rats with hapten-induced colitis.
AB  - Active hexose correlated compound (AHCC) is a product prepared from the mycelium
      of edible Basidiomycete fungi that contains oligosaccharides. Here we have
      studied the antiinflammatory effect of AHCC in the trinitrobenzenesulfonic acid
      (TNBS) model of colitis in rats. Rats received AHCC (100 or 500 mg/kg) daily
      starting 2 d before (pretreatment) colitis induction and were killed 6 d after
      the TNBS challenge. The status of the rats was assessed by morphological and
      biochemical methods. The effect of AHCC on the colonic microflora was also
      assessed by studying the bacteria profile in feces by standard culture
      techniques. AHCC administration attenuated colonic inflammation, improving rat
      weight, food intake, damage score, extension of necrosis, colonic weight, colonic
      weight-to-length ratio, myeloperoxidase and alkaline phosphatase activities,
      glutathione concentration, and the expression of proinflammatory cytokines and
      chemokines (IL-1beta, IL-1 receptor antagonist, TNF, and monocyte chemoattractant
      protein-1) and of mucins 2-4 and trefoil factor 3. The magnitude of the
      antiinflammatory effect of AHCC was similar to that of sulfasalazine (200 mg/kg).
      The study of colonic microflora indicated that rats treated with AHCC had higher
      aerobic and lactic acid bacteria counts as well as higher bifidobacteria counts,
      whereas clostridia were reduced when compared with the TNBS group. Therefore, our
      results indicate that AHCC is antiinflammatory and could be useful as a prebiotic
      to design functional foods for inflammatory bowel disease patients.

PMID- 17449586
TI  - Neonatal-age treatment with vitamin A delays postweaning vitamin A deficiency and
      increases the antibody response to T-cell dependent antigens in young adult rats
      fed a vitamin A-deficient diet.
AB  - Vitamin A supplementation for infants and young children is recommended by
      WHO/UNICEF for countries with a high prevalence of vitamin A deficiency, and
      vitamin A is often administered at immunization contacts. Using a rat model, we
      tested whether supplementation with vitamin A or other retinoids at the time of
      neonatal immunization has prospective benefit in terms of preventing postweaning
      vitamin A deficiency and promoting antibody responses to T-cell dependent (TD)
      antigens administered at the neonatal stage and at the young adult stage. Rats
      were treated orally on postnatal d 6-8 with oil (placebo control), vitamin A,
      retinoic acid, or a combination of both (VARA) (n > or = 12/group), and immunized
      with tetanus toxoid (TT) on d 7. The primary anti-TT response was measured on d
      21, after which weanling rats were fed the vitamin A-deficient diet until
      approximately 10 wk. At 8 wk, rats were immunized again with TT to determine the
      recall response, and with a novel TD antigen, keyhole limpet hemocyanin (KLH), to
      assess the adult primary response. None of the supplements affected the plasma
      titer of anti-TT immunoglobulin G (IgG) on d 21 (P = 0.25). However, neonatal-age
      supplementation with vitamin A or VARA at the young adult stage resulted in: >5
      times higher anti-TT IgG recall response (P < 0.01); 5- and 9-times higher anti
      KLH primary IgM and IgG responses, respectively (P < 0.05), and plasma retinol in
      the normal range (approximately 1.0 micromol/L vs. approximately 0.35 micromol/L
      in retinoic acid-treated and control groups, P < 0.0001). We conclude that early
      life supplementation with vitamin A or VARA can prospectively benefit the primary
      and recall antibody responses to TD antigens administered at the young adult
      stage, which may involve the maintenance of normal plasma retinol levels.

PMID- 17449587
TI  - Diet-induced obese mice have increased mortality and altered immune responses
      when infected with influenza virus.
AB  - Obesity is associated with an impaired immune response, an increased
      susceptibility to bacterial infection, and a chronic increase in proinflammatory
      cytokines such as IL-6 and TNFalpha. However, few studies have examined the
      effect of obesity on the immune response to viral infections. Because infection
      with influenza is a leading cause of morbidity and mortality worldwide, we
      investigated the effect of obesity on early immune responses to influenza virus
      exposure. Diet-induced obese and lean control C57BL/6 mice were infected with
      influenza A/PR8/34, and lung pathology and immune responses were examined at d 0
      (uninfected), 3, and 6, postinfection. Following infection, diet-induced obese
      mice had a significantly higher mortality rate than the lean controls and
      elevated lung pathology. Antiviral and proinflammatory cytokine mRNA production
      in the lungs of the infected mice was markedly different between obese and lean
      mice. IFNalpha and beta were only minimally expressed in the infected lungs of
      obese mice and there was a notable delay in expression of the proinflammatory
      cytokines IL-6 and TNFalpha. Additionally, obese mice had a substantial reduction
      in NK cell cytotoxicity. These data indicate that obesity inhibits the ability of
      the immune system to appropriately respond to influenza infection and suggests
      that obesity may lead to increased morbidity and mortality from viral infections.

PMID- 17449588
TI  - Estimated dietary flavonoid intake and major food sources of U.S. adults.
AB  - Estimating flavonoid intake is a first step toward documenting the protective
      effects of flavonoids against risk of chronic diseases. Although flavonoids are
      important dietary sources of antioxidants, insufficient data on the comprehensive
      food composition of flavonoids have delayed the assessment of dietary intake in a
      population. We aimed to estimate the dietary flavonoid intake in U.S. adults and
      its sociodemographic subgroups and to document major dietary sources of
      flavonoids. We expanded the recently released USDA Flavonoid Database to increase
      its correspondence with the 24-h dietary recall (DR) of the NHANES 1999-2002. We
      systematically assigned a particular food code to all foods that were prepared or
      processed similarly. This expanded database included 87% of fruits and fruit
      juices, 86% of vegetables, 75% of legumes, and, overall, 45% of all foods
      reported by the 24-h DR of the NHANES 1999-2002. Estimated mean daily total
      flavonoid intake, 189.7 mg/d, was mainly from flavan-3-ols (83.5%), followed by
      flavanones (7.6%), flavonols (6.8%), anthocyanidins (1.6%), flavones (0.8%), and
      isoflavones (0.6%). The flavonoid density of diets increased with age (P < 0.001)
      and income (P < 0.05). It was higher in women (P < 0.001), Caucasians (P <
      0.001), and vitamin supplement users (P < 0.001) and lower in adults with high
      levels of nonleisure time physical activity (P < 0.01) compared with their
      counterparts. The greatest daily mean intake of flavonoids was from the following
      foods: tea (157 mg), citrus fruit juices (8 mg), wine (4 mg), and citrus fruits
      (3 mg). The proposed relation between flavonoid intake and the prevention of
      chronic diseases needs further investigation using the estimates introduced in
      this study.

PMID- 17449589
TI  - The indicator amino acid oxidation method identified limiting amino acids in two
      parenteral nutrition solutions in neonatal piglets.
AB  - Recent studies using the indicator amino acid oxidation (IAAO) technique in TPN
      fed piglets and infants have been instrumental in defining parenteral amino acid
      requirements. None of the commercial products in use are ideal when assessed
      against these new data. Our objectives were to determine whether the oxidation of
      an indicator amino acid would decline with the addition of amino acids that were
      limiting in the diets of TPN-fed piglets, and to use this technique to identify
      limiting amino acids in a new amino acid profile. Piglets (n = 26) were
      randomized to receive TPN with amino acids provided by Vaminolact (VM) or by a
      new profile (NP). After 5 d of TPN administration, lysine oxidation was measured
      using a constant infusion of L- [1-(14)C]-lysine. Immediately following the first
      IAAO study, the piglets were further randomized within diet group to receive
      either 1) supplemental aromatic amino acids (AAA), 2) sulfur amino acids (SAA) or
      3) both (AAA+SAA) (n = 4-5 per treatment group). A second IAAO study was carried
      out 18 h later. In the first IAAO study, lysine oxidation was high for both
      groups (18 vs. 21% for VM and NP, respectively, P = 0.055). The addition of AAA
      to VM induced a 30% decline in lysine oxidation compared with baseline (P <
      0.01). Similarly, SAA added to NP lowered lysine oxidation by approximately 30%
      (P < 0.01). The application of the IAAO technique facilitates rapid evaluation of
      the amino acids that are limiting to protein synthesis in parenteral solutions.

PMID- 17449590
TI  - Acute ethanol exposure inhibits renal folate transport, but repeated exposure
      upregulates folate transport proteins in rats and human cells.
AB  - Deficiency of folate in heavy-drinking alcoholic populations can occur partly
      because of an increased urinary folate excretion. Ethanol directly reduces the
      reabsorption of folate in the renal proximal tubule (PT) by acting on either of 2
      folate transport proteins, the reduced folate carrier (RFC) and the folate
      receptor (FR). This study was designed to determine the effects of ethanol on the
      transport of folate by PT cells and to examine the effects of ethanol on RFC and
      the FR protein expression. Normal human PT (HPT) cells were cultured on membrane
      inserts to study intracellular transport of 5-methyltetrahydrofolate from the
      apical or basolateral direction in the presence of ethanol [11-109 mmol/L (50-500
      mg/dL)]. The long-term effect of ethanol on the renal folate transport protein
      content was determined by western blot in treated HPT cells and in vivo in rats
      pair-fed control diets or ethanol-containing liquid diets. A 1-h treatment of HPT
      cells with ethanol (> or = 65 mmol/L) reduced the apically directed transport of
      folate by 20-25% without affecting the basolateral transport. A 5-d exposure of
      HPT cells to ethanol dose-dependently increased the content of both the FR and
      RFC proteins, with a greater effect on the RFC. Similarly, a 14-d exposure of
      rats to ethanol increased the in vivo expression of both the RFC and FR. These
      studies demonstrate that ethanol decreases the reabsorptive transport of folate
      by renal PT cells, which would increase urinary folate excretion. In contrast,
      subchronic exposure of PT cells, both in vivo and in vitro, to folate-depleting
      concentrations of ethanol leads to an upregulation of the 2 folate transport
      proteins. The increase in folate transporters partly counteracts the inhibitory
      effects of ethanol on folate transport activity, which explains the lower
      magnitude of ethanol's effect on transport with subchronic exposure compared with
      that with acute exposure.

PMID- 17449591
TI  - Relation between plasma enterodiol and enterolactone and dietary intake of
      lignans in a Dutch endoscopy-based population.
AB  - Enterolignans are phytoestrogenic compounds derived from the conversion of
      dietary lignans by the intestinal microflora that may be protective against
      cardiovascular diseases and cancer. To evaluate the use of enterolignans as
      biomarkers of dietary lignan intake, we studied the relation between plasma and
      dietary lignans. We determined the dietary intake of 4 lignans
      (secoisolariciresinol (SECO), matairesinol (MAT), pinoresinol, and lariciresinol)
      using the European Prospective Investigation into Cancer and Nutrition FFQ, and
      plasma enterodiol (END) and enterolactone (ENL) concentrations were determined by
      liquid chromatography-tandem mass spectrometry. The population consisted of 637
      men and women, aged 19-75 y, participating in a case-control study on colorectal
      adenomas. Participants did not use antibiotics in the preceding calendar year. We
      found a modest association between lignan intake and plasma END (Spearman r =
      0.09, P = 0.03) and ENL (Spearman r = 0.18, P <0.001). The correlation of total
      lignan intake with plasma enterolignans was slightly stronger than that of only
      SECO plus MAT. The plasma concentrations of both END and ENL were associated with
      intake of dietary fiber and vegetable protein but not with intake of other
      macronutrients. The relation between lignan intake and plasma END was modulated
      by age and previous use of antibiotics, whereas for ENL, it was modulated by
      weight, current smoking, and frequency of defecation. However, even when we
      included these nondietary factors in the regression models, the explained
      variance in plasma END and ENL remained low (2 and 13%, respectively).

PMID- 17449592
TI  - Vitamin A supplementation enhances infants' immune responses to hepatitis B
      vaccine but does not affect responses to Haemophilus influenzae type b vaccine.
AB  - Vitamin A supplementation reduces child mortality and severe morbidity in less
      developed countries, and the Expanded Program on Immunization (EPI) offers an
      ideal opportunity to deliver supplements in developing countries. High-dose
      vitamin A supplementation has been shown to have no effect on the immunogenicity
      of oral polio vaccine, tetanus toxoid, pertussis, or on measles vaccine given at
      9 mo, but a negative effect on measles vaccine administered at 6 mo and a
      potentiating effect on diphtheria vaccine. Its effect on the antibody response to
      hepatitis B and Haemophilus influenzae type b antigens has not yet been
      established. To assess these effects, the present trial was carried out in the
      Offinso district of Ghana; 1077 infants were enrolled shortly after birth and
      randomized either to receive or not to receive 15 mg retinol equivalent with
      vitamin A together with the pentavalent "diphtheria-polio-tetanus-Haemophilus
      influenzae b-hepatitis B" vaccine at 6, 10, and 14 wk of age. All mothers
      received a postpartum supplement of 120 mg retinol equivalent vitamin A as per
      national policy. Blood samples were taken from infants at 6 and 18 wk of age. The
      results are based on 888 infants (82.4%) who completed the trial. The vitamin A
      supplementation did not affect the immune response to Haemophilus influenzae type
      b, but there was a significant improvement in the immune response to hepatitis B
      vaccine (93.9 vs. 90.2%, P = 0.04). However, given the high percentage of infants
      with seroprotection in the control group, it is doubtful that inclusion of
      vitamin A in the EPI would be justified on these grounds alone.

PMID- 17449593
TI  - Vitamin B-12 deficiency is prevalent in 35- to 64-year-old Chinese adults.
AB  - Low vitamin B-12 status alone, or in combination with low folate status, is
      related to neural tube defects (NTD) and hyperhomocysteinemia, a risk factor for
      atherosclerotic disease, but little is known about vitamin B-12 status in Chinese
      adults. In a cross-sectional study, we measured plasma vitamin B-12 in 2407
      apparently healthy Chinese men and women, 35-64 y old, living in the south and
      the north of China. Plasma vitamin B-12 concentrations were lower among the
      northerners than the southerners (geometric means, 209 vs. 309 pmol/L, P <
      0.001). Controlling for gender, age, season (spring and fall), and area (urban
      and rural) had little impact on the difference. We estimated that 11% of the
      southerners and 39% of the northerners had plasma vitamin B-12 concentrations
      <185 pmol/L, a level to define vitamin B-12 deficiency. Within each region, men
      had lower plasma vitamin B-12 concentrations and higher prevalence of vitamin B
      12 deficiency than women (279 vs. 333 pmol/L and 15 vs. 8% in the south; 192 vs.
      233 pmol/L and 47 vs. 34% in the north; P < 0.001 for all the differences). Low
      intakes of animal-based food, especially fish and dairy products, were
      significantly associated with vitamin B-12 deficiency. In the north, 59% of the
      participants were deficient in either folate (<6.8 nmol/L) or vitamin B-12, and
      17% had deficiency in both. The corresponding rates were 16 and 1% in the
      southerners. To our knowledge, our findings provide the first evidence that
      vitamin B-12 deficiency is common in 35- to 64-y-old Chinese adults, especially
      in the north. Further studies are needed to evaluate the health effects and
      possible intervention strategies in areas where B-12 vitamin deficiency is
      common.

PMID- 17449594
TI  - High levels of low energy reporting on 24-hour recalls and three questionnaires
      in an elderly low-socioeconomic status population.
AB  - Studies of low energy reporting in the elderly are limited, yet changes in energy
      balance and the incidence of chronic disease make this a critical time to assess
      energy intake in this population. The objective of this study was to assess low
      energy reporting on 24-h recalls (24HR), a FFQ, a picture sort FFQ (PSFFQ), and a
      meal pattern questionnaire (MPQ), and to relate low energy reporting status to
      personal characteristics and dietary characteristics, including the Healthy
      Eating Index. Monthly 24HR were completed over 6 mo, followed by 3 interviewer
      administered questionnaires. The Goldberg equation was used to determine
      reporting status for the dietary assessment methods among older, rural, low
      socioeconomic status, white, African American, and Native American men and women.
      The relations of variables of interest to low energy reporting were considered
      one at a time and in multiple logistic regression models. The percentage of
      participants classified as accurate reporters varied from 40% (FFQ) to 63%
      (PSFFQ) among men and 60% (24HR, PSFFQ, MPQ) to 63% (FFQ) among women; high
      energy reporting was observed on the MPQ. Low energy reporters on the FFQ tended
      to be men and to be overweight or obese (P < 0.05). Underreporting seemed to be
      due to omitting foods from major food groups as well as from omitting
      discretionary energy foods. There was a high degree of low energy reporting in
      this population, particularly by men, even with six 24HR.

PMID- 17449595
TI  - Variations in plasma phytoestrogen concentrations in European adults.
AB  - Dietary phytoestrogens may play a role in chronic disease occurrence. The aim of
      our study was to assess the variability of plasma concentrations in European
      populations. We included 15 geographical regions in 9 European countries
      (Denmark, France, Germany, Greece, Italy, Spain, Sweden, The Netherlands, and UK)
      and a 16th region, Oxford, UK, where participants were recruited from among
      vegans and vegetarians. All subjects were participants of the European
      Prospective Investigation into Cancer and Nutrition (EPIC). Plasma concentrations
      of 3 isoflavones (daidzein, genistein, and glycitein), 2 metabolites of daidzein
      [O-desmethylangolensin (O-DMA) and equol] and 2 mammalian lignans (enterodiol and
      enterolactone) were measured in 1414 participants. We computed geometric means
      for each region and used multivariate regression analysis to assess the influence
      of region, adjusted for gender, age, BMI, alcohol intake, smoking status, and
      laboratory batch. Many subjects had concentrations below the detection limit [0.1
      microg/L (0.4 nmol/L)] for glycitein (80%), O-DMA (73%) and equol (62%).
      Excluding subjects from Oxford, UK, the highest concentrations of isoflavones
      were in subjects from the Netherlands and Cambridge, UK [2-6 microg/L (7-24
      nmol/L); P < 0.05], whereas concentrations for lignans were highest in Denmark [8
      microg/L (27 nmol/L); P < 0.05]. Isoflavones varied 8- to 13-fold, whereas
      lignans varied 4-fold. In the vegetarian/vegan cohort of Oxford, concentrations
      of isoflavones were 5-50 times higher than in nonvegetarian regions. Region was
      the most important determinant of plasma concentrations for all 7 phytoestrogens.
      Despite the fact that plasma concentrations of phytoestrogens in Europe were low
      compared with Asian populations, they varied substantially among subjects from
      the 16 different regions.

PMID- 17449596
TI  - Customary use of plant sterol and plant stanol enriched margarine is associated
      with changes in serum plant sterol and stanol concentrations in humans.
AB  - The consumption of products enriched with plant sterol or stanol esters lowers
      serum total and LDL-cholesterol concentrations, thereby most likely reducing the
      risk of coronary heart disease. However, using plant sterol (not plant stanol)
      enriched products elevates serum plant sterol concentrations in humans. This may
      be unwanted because health effects of elevated serum plant sterol concentrations
      are still controversial. Within postlaunch monitoring of functional foods, we
      compared serum plant sterol and plant stanol concentrations among users of plant
      sterol (n = 67) or plant stanol (n = 13) enriched margarines with those of
      matched nonusers (n = 81) in the ongoing Dutch Doetinchem cohort study. Subjects
      (aged 29-67 y) were examined in 1994-1998 (before the introduction of enriched
      margarines) and re-examined in 1999-2003. Serum concentrations of plant sterols
      and stanols were measured in samples from nonfasting subjects by GLC-MS. Intake
      of plant sterols was 1.1 +/- 0.6 g/d and was associated with a decrease of serum
      total cholesterol concentration of 0.25 +/- 0.91 mmol/L (4%, P < 0.05), a change
      that differed (P < 0.05) from the nonsignificant increase in nonusers (+2%, 0.12
      +/- 0.78 mmol/L, P = 0.16). Cholesterol-standardized serum sitosterol and
      campesterol increased in plant sterol users by 22% (P < 0.0001) and 103% (P <
      0.0001), respectively. Cholesterol-standardized serum sitostanol and campestanol
      increased in plant stanol users by 197% (P = 0.02) and 196% (P = 0.01). To our
      knowledge, these data are the first to show changes in serum cholesterol, plant
      sterol, and plant stanol concentrations after (long-term) consumption of plant
      sterol and stanol enriched margarines in a free-living population in a
      nonexperimental setting. Whether the increased serum sterol concentrations result
      in adverse side effects needs to be investigated in future postlaunch monitoring
      studies.

PMID- 17449597
TI  - Prevalent vitamin B-12 deficiency in twelve-month-old Guatemalan infants is
      predicted by maternal B-12 deficiency and infant diet.
AB  - Approximately one-third of low-income women and children studied in Guatemala are
      reported to have deficient (<148 pmol/L) or marginal (148-220 pmol/L) plasma
      vitamin B-12 concentrations. Because vitamin B-12 deficiency can adversely affect
      infant development and cognitive function, the present study examined predictors
      of deficient plasma vitamin B-12 concentrations at the age of 12 mo. Analyses
      were performed on baseline data from a randomized clinical trial in 304
      Guatemalan infants, 80% of whom were partially breast-fed, and their mothers.
      Exclusion criteria for infants included twins, severe stunting or moderate
      wasting, reported major health problems, severe developmental delay, hemoglobin
      <95 g/L, maternal age <17 y, and maternal pregnancy >3 mo. Data collected
      included socio-economic status, infant anthropometry, vitamin B-12 intake from
      complementary foods, and breast-feeding frequency reported by mothers. A complete
      blood count and plasma vitamin B-12, folate, ferritin, and C-reactive protein
      were measured. Deficient or marginal plasma vitamin B-12 concentrations were
      found in 49% of infants and 68% of mothers. The mean intake of maternal vitamin B
      12 was 3.1 microg/d, and infants consumed 2.2 microg/d from complementary foods.
      In linear regression analysis, infant plasma B-12 concentration was strongly and
      positively associated with maternal plasma vitamin B-12 and B-12 intake from
      complementary foods (predominantly powdered cow's milk), and inversely associated
      with frequency of breast-feeding and larger household size (P < 0.0001). Vitamin
      B-12 supplementation of lactating women, food fortification, and education to
      improve infant's vitamin B-12 status are potential interventions that can improve
      the vitamin B-12 status of mothers and infants in this population.

PMID- 17449598
TI  - Occupation is more important than rural or urban residence in explaining the
      prevalence of metabolic and cardiovascular disease risk in Guatemalan adults.
AB  - Diet and activity pattern changes consequent to urbanization are contributing to
      the global epidemic of cardiovascular disease; less research has focused on
      activity within rural populations. We studied 527 women and 360 men (25-42 y),
      all rural-born and currently residing in rural or urban areas of Guatemala. We
      further classified rural male occupations as agricultural or nonagricultural.
      Overweight status (BMI > or = 25 kg/m(2)) differed by residence/occupation among
      men (agricultural-rural, 27%; nonagricultural-rural, 44%; and urban, 55%; P<
      0.01) and women (rural, 58%; and urban, 68%; P= 0.04). A moderate-to-vigorous
      lifestyle was reported by 76, 37, and 20% of men (agricultural-rural,
      nonagricultural-rural, and urban, respectively; P< 0.01); most women were
      sedentary, with no difference by residence. Prevalence of the metabolic syndrome
      was 17, 24, and 28% in agricultural-rural, nonagricultural-rural, and urban men,
      respectively (P= 0.2), and 44 and 45% in rural and urban women (P= 0.4). Dietary
      variables were largely unassociated with adiposity or cardio-metabolic risk
      factors; physical activity was inversely associated with the percentage of body
      fat in men. Percent body fat was inversely associated with HDL-cholesterol, and
      positively associated with triglycerides, blood pressure, and the metabolic
      syndrome in both men and women, and with LDL-cholesterol and fasting glucose in
      women. Differences in physical activity level, mainly attributable to occupation,
      appear more important than residence, per se, in influencing the risk for
      cardiovascular disease among men; differences among these sedentary women are
      likely related to other factors associated with an urban environment.

PMID- 17449599
TI  - A food-based approach introducing orange-fleshed sweet potatoes increased vitamin
      A intake and serum retinol concentrations in young children in rural Mozambique.
AB  - Vitamin A deficiency is widespread and has severe consequences for young children
      in the developing world. Food-based approaches may be an appropriate and
      sustainable complement to supplementation programs. Orange-fleshed sweet potato
      (OFSP) is rich in beta-carotene and is well accepted by young children. In an
      extremely resource poor area in Mozambique, the effectiveness of introduction of
      OFSP was assessed in an integrated agriculture and nutrition intervention, which
      aimed to increase vitamin A intake and serum retinol concentrations in young
      children. The 2-y quasi-experimental intervention study followed households and
      children (n = 741; mean age 13 mo at baseline) through 2 agricultural cycles. In
      y 2, 90% of intervention households produced OFSP, and mean OFSP plot size in
      intervention areas increased from 33 to 359 m(2). Intervention children (n = 498)
      were more likely than control children (n = 243) to eat OFSP 3 or more d in the
      last wk (55% vs. 8%, P < 0.001) and their vitamin A intakes were much higher than
      those of control children (median 426 vs. 56 microg retinol activity equivalent,
      P < 0.001). Controlling for infection/inflammation and other confounders, mean
      serum retinol increased by 0.100 micromol/L (SEM 0.024; P < 0.001) in
      intervention children and did not increase significantly in control subjects.
      Integrated promotion of OFSP can complement other approaches and contribute to
      increases in vitamin A intake and serum retinol concentrations in young children
      in rural Mozambique and similar areas in Sub-Saharan Africa.

PMID- 17449600
TI  - Malnutrition and morbidity are higher in children who are missed by periodic
      vitamin A capsule distribution for child survival in rural Indonesia.
AB  - Universal periodic high-dose vitamin A capsule distribution is a cost-effective
      intervention to increase child survival in developing countries. It is unclear
      whether children who are missed by the program are at higher risk for
      malnutrition and infectious disease morbidity. Based on data from the Nutritional
      Surveillance System, we compared nutritional status and other health indicators
      of children aged 12-59 mo in rural Indonesia who did and did not receive a
      vitamin A capsule within the last 6 mo. A total of 241,087 of 335,034 children
      (72.0%) received a vitamin A capsule between 1999 and 2003. In children who did
      and did not receive a vitamin A capsule, respectively, the proportion with weight
      for-age, height-for-age, and weight-for-height Z scores <-2 were 37.0 vs. 42.5%,
      39.2 vs. 45.6%, and 6.9 vs. 7.4% (P < 0.0001). Similarly, the proportion with
      anemia, diarrhea during the last wk, current diarrhea, and current fever was 49.2
      vs. 54.8%, 6.7 vs. 8.4%, 4.4 vs. 6.0%, and 1.4 vs. 1.7% (P < 0.0001). Children
      who did not receive vitamin A were also less likely to have received childhood
      immunizations and belonged to families with higher infant and under-5-y child
      mortality than children who receive vitamin A. Although a lack of access to other
      public health interventions and demographic factors may also contribute to the
      rate of malnutrition in children missed by the vitamin A capsule program, it is
      likely that increased coverage of vitamin A supplementation would help to
      maximize the benefits for child survival.

PMID- 17449601
TI  - Host-pathogen interactions: can micronutrients tip the balance?
AB  - Nutrients are essential to the human host and to its invading pathogens. The
      purpose of this International Nutrition Council symposium on Micronutrient
      Regulation of Host-Pathogen Interactions held at Experimental Biology 2006 was to
      examine new knowledge about the mechanisms by which certain limiting
      micronutrients can mediate the balance of power between the human host and its
      numerous potential pathogens. In this introductory article, we briefly review how
      competition for nutrients is critical to the survival of both host and pathogen
      and describe some of the evolved mechanisms by which each attempts to gain
      supremacy over the other. We provide examples of how the presence or absence of
      certain mechanisms for nutrient acquisition can govern the niche specificity of
      organisms. We then describe some of the extensive evidence suggesting that, of
      all the nutrients, iron plays an especially crucial role in host-pathogen
      interactions. To this end, we provide a reminder of early studies suggesting that
      universal iron administration under conditions of high pathogen exposure may lead
      to adverse consequences. Finally, we provide some cautionary tales in the form of
      intervention studies in which the administration of other micronutrients yielded
      unpredicted adverse effects. These lessons emphasize the need to step back from
      an unbalanced concentration of research funds on empirical trials (often built on
      an inadequate theoretical basis) and toward a greater concentration on integrated
      clinical research into nutrient effects on host defenses and pathogen virulence.

PMID- 17449602
TI  - Selenium and vitamin E status: impact on viral pathogenicity.
AB  - Selenium (Se), an essential trace element, and vitamin E, a lipid soluble
      antioxidant, are important mediators for protection against oxidative stress.
      Recent work has demonstrated that deficiencies in either Se or vitamin E result
      in increased viral pathogenicity and altered immune responses. Furthermore,
      deficiencies in either Se or vitamin E results in specific viral mutations,
      changing relatively benign viruses into virulent ones. Thus, host nutritional
      status should be considered a driving force for the emergence of new viral
      strains or newly pathogenic strains of known viruses.

PMID- 17449603
TI  - Host-pathogen interactions: the role of iron.
AB  - Iron is essential for both host and pathogen, and complex systems of acquisition
      and utilization have evolved in competition. Our increasing knowledge of the
      basic mechanisms of homeostasis and their adaptation during deficiency, overload,
      and infection indicate that iron is a key regulator of host pathogen
      interactions. This review concentrated on the clinical and public health aspects
      of the interaction between the iron acquisition mechanisms of select pathogens of
      public health importance with host iron homeostasis. Knowledge of these
      interactions is essential in assessing likely morbidity responses to
      supplementation.

PMID- 17449604
TI  - Zinc: mechanisms of host defense.
AB  - Zinc deficiency in humans decreases the activity of serum thymulin (a thymic
      hormone), which is required for maturation of T-helper cells. T-helper 1 (Th(1))
      cytokines are decreased but T-helper 2 (Th(2)) cytokines are not affected by zinc
      deficiency in humans. This shift of Th(1) to Th(2) function results in cell
      mediated immune dysfunction. Because IL-2 production (Th(1) cytokine) is
      decreased, this leads to decreased activities of natural-killer cell and T
      cytolytic cells, which are involved in killing viruses, bacteria, and tumor
      cells. In humans, zinc deficiency may decrease the generation of new CD4+ T cells
      from the thymus. In cell culture studies (HUT-78, a Th(0) human malignant
      lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB
      (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to
      DNA are decreased and this results in decreased Th(1) cytokine production. In
      another study, zinc supplementation to humans decreased the gene expression and
      production of pro-inflammatory cytokines and decreased oxidative stress markers.
      In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency
      increased the levels of TNF-alpha, IL-1beta, and IL-8 cytokines and mRNA. In
      these cells, zinc induced A20, a zinc finger protein that inhibited NF-kappaB
      activation via tumor necrosis factor receptor associated factor pathway, and this
      decreased gene expression of pro-inflammatory cytokines and oxidative stress
      markers. We conclude that zinc has an important role in cell-mediated immune
      functions and also functions as antiinflammatory and antioxidant agent.

PMID- 17449605
TI  - Conversion of flavodoxin from holoenzyme to apoprotein during growth phase
      changes in Helicobacter pylori.
AB  - The catabolic pathway for flavodoxin has yet to be clarified for any bacterial
      species. In this study, we found that the flavin mononucleotide in the flavodoxin
      of Helicobacter pylori is degraded to riboflavin via the phosphomonoesterase
      activity of class C acid phosphatase. The result is a conversion of
      holoflavodoxin to apoflavodoxin.

PMID- 17449606
TI  - A copper-activated two-component system interacts with zinc and imipenem
      resistance in Pseudomonas aeruginosa.
AB  - The effects of copper (Cu) on trace metal and antibiotic resistance of
      Pseudomonas aeruginosa have been investigated. Cu treatments induced resistance
      not only to this metal but also, surprisingly, to zinc (Zn). Quantitative reverse
      transcription-PCR (qRT-PCR) revealed that after Cu treatment the transcription of
      the czcRS two-component system (TCS) operon was enhanced as well as that of the
      czcCBA operon encoding an efflux pump specific for zinc, cadmium, and cobalt. Cu
      treatments at the same time caused a decrease in the production of OprD porin,
      resulting in resistance to the carbapenem antibiotic imipenem. The CzcR regulator
      was known to repress oprD. However, Cu was still able to decrease the production
      of OprD and induce imipenem resistance in a czcRS knockout mutant. This strongly
      suggested that another Cu-dependent regulatory system was acting negatively on
      oprD expression. TCS regulator genes copR-copS have been shown to be involved in
      Cu tolerance in P. aeruginosa. qRT-PCR showed that overproduction of the CopR or
      of the CzcR regulator resulted in increased transcription of the czcC gene as
      well as in a decrease in oprD gene transcription, either in the wild-type strain
      or in the czcRS knockout mutant. Overproduction experiments suggest that a metal
      dependent mechanism operates at the posttranscriptional level to control the
      production of the CzcCBA efflux pump. This study shows that CopR is a new
      negative regulator of OprD porin and that it links Zn, Cu, and imipenem
      resistances by interacting with the CzcRS TCS.

PMID- 17449607
TI  - A polyomic approach to elucidate the fluoranthene-degradative pathway in
      Mycobacterium vanbaalenii PYR-1.
AB  - Mycobacterium vanbaalenii PYR-1 is capable of degrading a wide range of high
      molecular-weight polycyclic aromatic hydrocarbons (PAHs), including fluoranthene.
      We used a combination of metabolomic, genomic, and proteomic technologies to
      investigate fluoranthene degradation in this strain. Thirty-seven fluoranthene
      metabolites including potential isomers were isolated from the culture medium and
      analyzed by high-performance liquid chromatography, gas chromatography-mass
      spectrometry, and UV-visible absorption. Total proteins were separated by one
      dimensional gel and analyzed by liquid chromatography-tandem mass spectrometry in
      conjunction with the M. vanbaalenii PYR-1 genome sequence (http://jgi.doe.gov),
      which resulted in the identification of 1,122 proteins. Among them, 53 enzymes
      were determined to be likely involved in fluoranthene degradation. We integrated
      the metabolic information with the genomic and proteomic results and proposed
      pathways for the degradation of fluoranthene. According to our hypothesis, the
      oxidation of fluoranthene is initiated by dioxygenation at the C-1,2, C-2,3, and
      C-7,8 positions. The C-1,2 and C-2,3 dioxygenation routes degrade fluoranthene
      via fluorene-type metabolites, whereas the C-7,8 routes oxidize fluoranthene via
      acenaphthylene-type metabolites. The major site of dioxygenation is the C-2,3
      dioxygenation route, which consists of 18 enzymatic steps via 9-fluorenone-1
      carboxylic acid and phthalate with the initial ring-hydroxylating oxygenase,
      NidA3B3, oxidizing fluoranthene to fluoranthene cis-2,3-dihydrodiol. Nonspecific
      monooxygenation of fluoranthene with subsequent O methylation of
      dihydroxyfluoranthene also occurs as a detoxification reaction.

PMID- 17449608
TI  - Molecular characterization and subcellular localization of macrophage infectivity
      potentiator, a Chlamydia trachomatis lipoprotein.
AB  - Macrophage infectivity potentiator (MIP) was originally reported to be a
      chlamydial lipoprotein from experiments showing incorporation of radiolabeled
      palmitic acid into native and recombinant MIP; inhibition of posttranslational
      processing of recombinant MIP by globomycin, known to inhibit signal peptidase
      II; and solubility of native MIP in Triton X-114. However, the detailed
      structural characterization of the lipid moiety on MIP has never been fully
      elucidated. In this study, bioinformatics and mass spectrometry analysis, as well
      as radiolabeling and immunochemical experiments, were conducted to further
      characterize MIP structure and subcellular localization. In silico analysis
      showed that the amino acid sequence of MIP is conserved across chlamydial
      species. A potential signal sequence with a contained lipobox was identified, and
      a recombinant C20A variant was prepared by replacing the probable lipobox
      cysteine with an alanine. Both incorporation of U-(14)C-esterified glycerol and
      [U-(14)C]palmitic acid and posttranslational processing that was inhibitable by
      globomycin were observed for recombinant wild-type MIP but not for the
      recombinant C20A MIP variant. The fatty acid contents of native and recombinant
      MIP were analyzed by gas chromatography-mass spectrometry, and the presence of
      amide-linked fatty acids in recombinant MIP was investigated by alkaline
      methanolysis. These results demonstrated a lipid modification in MIP similar to
      that of other prokaryotic lipoproteins. In addition, MIP was detected in an outer
      membrane preparation of Chlamydia trachomatis elementary bodies and was shown to
      be present at the surfaces of elementary bodies by surface biotinylation and
      surface immunoprecipitation experiments.

PMID- 17449609
TI  - Comparative genome analysis of four magnetotactic bacteria reveals a complex set
      of group-specific genes implicated in magnetosome biomineralization and function.
AB  - Magnetotactic bacteria (MTB) are a heterogeneous group of aquatic prokaryotes
      with a unique intracellular organelle, the magnetosome, which orients the cell
      along magnetic field lines. Magnetotaxis is a complex phenotype, which depends on
      the coordinate synthesis of magnetosomes and the ability to swim and orient along
      the direction caused by the interaction with the Earth's magnetic field. Although
      a number of putative magnetotaxis genes were recently identified within a
      conserved genomic magnetosome island (MAI) of several MTB, their functions have
      remained mostly unknown, and it was speculated that additional genes located
      outside the MAI might be involved in magnetosome formation and magnetotaxis. In
      order to identify genes specifically associated with the magnetotactic phenotype,
      we conducted comparisons between four sequenced magnetotactic Alphaproteobacteria
      including the nearly complete genome of Magnetospirillum gryphiswaldense strain
      MSR-1, the complete genome of Magnetospirillum magneticum strain AMB-1, the
      complete genome of the magnetic coccus MC-1, and the comparative-ready
      preliminary genome assembly of Magnetospirillum magnetotacticum strain MS-1
      against an in-house database comprising 426 complete bacterial and archaeal
      genome sequences. A magnetobacterial core genome of about 891 genes was found
      shared by all four MTB. In addition to a set of approximately 152 genus-specific
      genes shared by the three Magnetospirillum strains, we identified 28 genes as
      group specific, i.e., which occur in all four analyzed MTB but exhibit no (MTB
      specific genes) or only remote (MTB-related genes) similarity to any genes from
      nonmagnetotactic organisms and which besides various novel genes include nearly
      all mam and mms genes previously shown to control magnetosome formation. The MTB
      specific and MTB-related genes to a large extent display synteny, partially
      encode previously unrecognized magnetosome membrane proteins, and are either
      located within (18 genes) or outside (10 genes) the MAI of M. gryphiswaldense.
      These genes, which represent less than 1% of the 4,268 open reading frames of the
      MSR-1 genome, as yet are mostly of unknown functions but are likely to be
      specifically involved in magnetotaxis and, thus, represent prime targets for
      future experimental analysis.

PMID- 17449610
TI  - Role of Escherichia coli DNA polymerase I in conferring viability upon the
      dnaN159 mutant strain.
AB  - The Escherichia coli dnaN159 allele encodes a mutant form of the beta-sliding
      clamp (beta159) that is impaired for interaction with the replicative DNA
      polymerase (Pol), Pol III. In addition, strains bearing the dnaN159 allele
      require functional Pol I for viability. We have utilized a combination of genetic
      and biochemical approaches to characterize the role(s) played by Pol I in the
      dnaN159 strain. Our findings indicate that elevated levels of Pol I partially
      suppress the temperature-sensitive growth phenotype of the dnaN159 strain. In
      addition, we demonstrate that the beta clamp stimulates the processivity of Pol I
      in vitro and that beta159 is impaired for this activity. The reduced ability of
      beta159 to stimulate Pol I in vitro correlates with our finding that single
      stranded DNA (ssDNA) gap repair is impaired in the dnaN159 strain. Taken
      together, these results suggest that (i) the beta clamp-Pol I interaction may be
      important for proper Pol I function in vivo and (ii) in the absence of Pol I,
      ssDNA gaps may persist in the dnaN159 strain, leading to lethality of the dnaN159
      DeltapolA strain.

PMID- 17449611
TI  - Genetic dissection of specificity determinants in the interaction of HPr with
      enzymes II of the bacterial phosphoenolpyruvate:sugar phosphotransferase system
      in Escherichia coli.
AB  - The histidine protein (HPr) is the energy-coupling protein of the
      phosphoenolpyruvate (PEP)-dependent carbohydrate:phosphotransferase system (PTS),
      which catalyzes sugar transport in many bacteria. In its functions, HPr interacts
      with a number of evolutionarily unrelated proteins. Mainly, it delivers
      phosphoryl groups from enzyme I (EI) to the sugar-specific transporters (EIIs).
      HPr proteins of different bacteria exhibit almost identical structures, and,
      where known, they use similar surfaces to interact with their target proteins.
      Here we studied the in vivo effects of the replacement of HPr and EI of
      Escherichia coli with the homologous proteins from Bacillus subtilis, a gram
      positive bacterium. This replacement resulted in severe growth defects on PTS
      sugars, suggesting that HPr of B. subtilis cannot efficiently phosphorylate the
      EIIs of E. coli. In contrast, activation of the E. coli BglG regulatory protein
      by HPr-catalyzed phosphorylation works well with the B. subtilis HPr protein.
      Random mutations were introduced into B. subtilis HPr, and a screen for improved
      growth on PTS sugars yielded amino acid changes in positions 12, 16, 17, 20, 24,
      27, 47, and 51, located in the interaction surface of HPr. Most of the changes
      restore intermolecular hydrophobic interactions and salt bridges normally formed
      by the corresponding residues in E. coli HPr. The residues present at the
      targeted positions differ between HPrs of gram-positive and -negative bacteria,
      but within each group they are highly conserved. Therefore, they may constitute a
      signature motif that determines the specificity of HPr for either gram-negative
      or -positive EIIs.

PMID- 17449612
TI  - Multiple controls regulate the expression of mobE, an HNH homing endonuclease
      gene embedded within a ribonucleotide reductase gene of phage Aeh1.
AB  - Mobile genetic elements have the potential to influence the expression of genes
      surrounding their insertion site upon invasion of a genome. Here, we examine the
      transcriptional organization of a ribonucleotide reductase operon (nrd) that has
      been invaded by an HNH family homing endonuclease, mobE. In Aeromonas hydrophila
      phage Aeh1, mobE has inserted into the large-subunit gene (nrdA) of aerobic
      ribonucleotide reductase (RNR), splitting it into two smaller genes, nrdA-a and
      nrdA-b. This gene organization differs from that in phages T4, T6, RB2, RB3,
      RB15, and LZ7, where mobE is inserted in the nrdA-nrdB intergenic region. We
      present evidence that the expression of Aeh1 mobE is regulated by
      transcriptional, posttranscriptional, and translational controls. An Aeh1
      specific late promoter drives expression of mobE, but strikingly the mobE
      transcript is processed internally at an RNase E-like site. We also identified a
      putative stem-loop structure upstream of mobE that sequesters the mobE ribosome
      binding site, presumably acting to down regulate MobE translation. Moreover, our
      transcriptional analyses indicate that the surrounding nrd genes of phage Aeh1
      are expressed by a different strategy than are the corresponding phage T4 genes
      and that transcriptional readthrough is the only mechanism by which the
      promoterless Aeh1 nrdB gene is expressed. We suggest that the occurrence of
      multiple layers of control to limit the expression of mobE to late in the Aeh1
      infection cycle is an adaptation of Aeh1 to reduce any effects on expression of
      the surrounding nrd genes early in phage infection when RNR function is critical.

PMID- 17449613
TI  - Genes, enzymes, and regulation of para-cresol metabolism in Geobacter
      metallireducens.
AB  - In aerobic and facultatively anaerobic bacteria, the degradation of para-cresol
      (p-cresol) involves the initial hydroxylation to p-hydroxybenzyl alcohol by water
      catalyzed by the soluble, periplasmatic flavocytochrome p-cresol
      methylhydroxylase (PCMH; alpha(2)beta(2) composition). In denitrifying bacteria
      the further metabolism proceeds via oxidation to p-hydroxybenzoate, the formation
      of p-hydroxybenzoyl-coenzyme A (CoA), and the subsequent dehydroxylation of the
      latter to benzoyl-CoA by reduction. In contrast, the strictly anaerobic
      Desulfobacterium cetonicum degrades p-cresol by addition to fumarate, yielding p
      hydroxybenzylsuccinate. In this work, in vitro enzyme activity measurements
      revealed that the obligately anaerobic Geobacter metallireducens uses the p
      cresol degradation pathway of denitrifying bacteria. Surprisingly, PCMH, which is
      supposed to catalyze both p-cresol hydroxylation and p-hydroxybenzyl alcohol
      oxidation to the corresponding aldehyde, was located in the membrane fraction.
      The alpha subunit of the enzyme was present in two isoforms, suggesting an
      alphaalpha'beta(2) composition. We propose that the unusual asymmetric
      architecture and the membrane association of PCMH might be important for
      alternative electron transfer routes to either cytochrome c (in the case of p
      cresol oxidation) or to menaquinone (in the case of p-hydroxybenzyl alcohol
      oxidation). Unusual properties of further enzymes of p-cresol metabolism, p
      hydroxybenzoate-CoA ligase, and p-hydroxybenzoyl-CoA reductase were identified
      and are discussed. A proteomic approach identified a gene cluster comprising most
      of the putative structural genes for enzymes involved in p-cresol metabolism (pcm
      genes). Reverse transcription-PCR studies revealed a different regulation of
      transcription of pcm genes and the corresponding enzyme activities, suggesting
      the presence of posttranscriptional regulatory elements.

PMID- 17449614
TI  - pmrA(Con) confers pmrHFIJKL-dependent EGTA and polymyxin resistance on msbB
      Salmonella by decorating lipid A with phosphoethanolamine.
AB  - Mutations in pmrA were recombined into Salmonella strain ATCC 14028 msbB to
      determine if pmrA-regulated modifications of lipopolysaccharide could suppress
      msbB growth defects. A mutation that functions to constitutively activate pmrA
      [pmrA(Con)] suppresses msbB growth defects on EGTA-containing media. Lipid A
      structural analysis showed that Salmonella msbB pmrA(Con) strains, compared to
      Salmonella msbB strains, have increased amounts of palmitate and
      phosphoethanolamine but no aminoarabinose addition, suggesting that
      aminoarabinose is not incorporated into msbB lipid A. Surprisingly, loss-of
      function mutations in the aminoarabinose biosynthetic genes restored EGTA and
      polymyxin sensitivity to Salmonella msbB pmrA(Con) strains. These blocks in
      aminoarabinose biosynthesis also prevented lipid A phosphoethanolamine
      incorporation and reduced the levels of palmitate addition, indicating previously
      unknown roles for the aminoarabinose biosynthetic enzymes. Lipid A structural
      analysis of the EGTA- and polymyxin-resistant triple mutant msbB pmrA(Con)
      pagP::Tn10, which contains phosphoethanolamine but no palmitoylated lipid A,
      suggests that phosphoethanolamine addition is sufficient to confer EGTA and
      polymyxin resistance on Salmonella msbB strains. Additionally, palmitoylated
      lipid A was observed only in wild-type Salmonella grown in the presence of salt
      in rich media. Thus, we correlate EGTA resistance and polymyxin resistance with
      phosphoethanolamine-decorated lipid A and demonstrate that the aminoarabinose
      biosynthetic proteins play an essential role in lipid A phosphoethanolamine
      addition and affect lipid A palmitate addition in Salmonella msbB strains.

PMID- 17449615
TI  - Translational regulation of the Escherichia coli stress factor RpoS: a role for
      SsrA and Lon.
AB  - Escherichia coli cell viability during starvation is strongly dependent on the
      expression of the rpoS gene, encoding the RpoS sigma subunit of RNA polymerase.
      RpoS abundance has been reported to be regulated at many levels, including
      transcription initiation, translation, and protein stability. The regulatory RNA
      SsrA (or tmRNA) has both tRNA and mRNA activities, relieving ribosome stalling
      and cotranslationally tagging proteins. We report here that SsrA is needed for
      the correct high-level translation of RpoS. The ATP-dependent protease Lon was
      also found to negatively affect RpoS translation, but only at low temperature. We
      suggest that SsrA may indirectly improve RpoS translation by limiting ribosome
      stalling and depletion of some component of the translation machinery.

PMID- 17449616
TI  - Regulation of the Pseudomonas aeruginosa quorum-sensing regulator VqsR.
AB  - Bacteria communicate with each other to regulate cell density-dependent gene
      expression via a quorum-sensing (QS) cascade. In Pseudomonas aeruginosa, two
      known QS systems, las and rhl, control the expression of many factors that relate
      to virulence, pathogenicity, and biofilm development. Microarray studies of the
      las and rhl regulons led to our hypothesis that a complicated hierarchy in the QS
      regulon is composed of multiple transcriptional regulators. Here, we examined a
      QS-regulated gene, vqsR, which encodes a probable transcriptional regulator with
      a putative 20-bp operator sequence (las box) upstream. The transcriptional start
      site for vqsR was determined. The vqsR promoter was identified by examining a
      series of vqsR promoter-lacZ fusions. In addition, an Escherichia coli system
      where either LasR or RhlR protein was expressed from a plasmid indicated that the
      las system was the dominant regulator for vqsR. Electrophoretic mobility shift
      assays (EMSA) demonstrate that purified LasR protein binds directly to the vqsR
      promoter in the presence of 3O-C12-HSL. Point mutational analysis of the vqsR las
      box suggests that positions 3 and 18 in the las box are important for vqsR
      transcription, as assayed with a series of vqsRp-lacZ fusions. EMSA also shows
      that positions 3 and 18 are important for binding between the vqsR promoter and
      LasR. Our results demonstrate that the las system directly regulates vqsR, and
      certain nucleotides in the las box are crucial for LasR binding and activation of
      the vqsR promoter.

PMID- 17449617
TI  - Environmental regulation of Pseudomonas aeruginosa PAO1 Las and Rhl quorum
      sensing systems.
AB  - The lasI-lasR and the rhlI-rhlR quorum-sensing systems in Pseudomonas aeruginosa
      regulate the expression of numerous cellular and secreted virulence factor genes
      and play important roles in the development of biofilms. The las and rhl systems
      themselves are known to be directly or indirectly regulated by a number of
      transcriptional regulators, and consequently, their expression is sensitive to
      environmental conditions. In this report, the activities of these two quorum
      sensing systems have been examined systematically under 46 growth conditions, and
      the regulation by environmental conditions has been investigated. The relative
      timing and strength of expression of these two systems varied significantly under
      different conditions, which contrasts with the notion of a preset hierarchy with
      these two systems in P. aeruginosa. Depending on the growth conditions, the
      correlation between each synthase and its cognate transcriptional regulator also
      varied, suggesting that the transcription of these genes independently allows for
      further fine tuning of each system. Finally, we observe that the activities of
      both the lasI-lasR and the rhlI-rhlR quorum-sensing systems were dramatically
      enhanced in the presence of extracts of sputum samples from cystic fibrosis
      patients.

PMID- 17449619
TI  - Localization of PcsB of Streptococcus pneumoniae and its differential expression
      in response to stress.
AB  - PcsB of Streptococcus pneumoniae is an essential hydrolase involved in the
      separation of dividing cells. In this study, it was found that PcsB localizes to
      the plasma membrane and is released into the growth environment, yet it is
      detectable on the pneumococcal surface by flow cytometry analysis. High
      temperature and osmolarity led to upregulation of pcsB expression.

PMID- 17449618
TI  - The NsrR regulon of Escherichia coli K-12 includes genes encoding the hybrid
      cluster protein and the periplasmic, respiratory nitrite reductase.
AB  - Successful pathogens must be able to protect themselves against reactive nitrogen
      species generated either as part of host defense mechanisms or as products of
      their own metabolism. The regulatory protein NsrR (a member of the Rrf2 family of
      transcription factors) plays key roles in this stress response. Microarray
      analysis revealed that NsrR represses nine operons encoding 20 genes in
      Escherichia coli MG1655, including the hmpA, ytfE, and ygbA genes that were
      previously shown to be regulated by NsrR. Novel NsrR targets revealed by this
      study include hcp-hcr (which were predicted in a recent bioinformatic study to be
      NsrR regulated) and the well-studied nrfA promoter that directs the expression of
      the periplasmic respiratory nitrite reductase. Conversely, transcription from the
      ydbC promoter is strongly activated by NsrR. Regulation of the nrf operon by NsrR
      is consistent with the ability of the periplasmic nitrite reductase to reduce
      nitric oxide and hence protect against reactive nitrogen species. Gel retardation
      assays were used to show that both FNR and NarL bind to the hcp promoter. The
      expression of hcp and the contiguous gene hcr is not induced by hydroxylamine. As
      hmpA and ytfE encode a nitric oxide reductase and a mechanism to repair iron
      sulfur centers damaged by nitric oxide, the demonstration that hcp-hcr, hmpA, and
      ytfE are the three transcripts most tightly regulated by NsrR highlights the
      possibility that the hybrid cluster protein, HCP, might also be part of a defense
      mechanism against reactive nitrogen stress.

PMID- 17449620
TI  - Augmented expression of polysaccharide intercellular adhesin in a defined
      Staphylococcus epidermidis mutant with the small-colony-variant phenotype.
AB  - While coagulase-negative staphylococci (CoNS), with their ability to form a
      thick, multilayered biofilm on foreign bodies, have been identified as the major
      cause of implant-associated infections, no data are available about biofilm
      formation by staphylococcal small-colony variants (SCVs). In the past years, a
      number of device-associated infections due to staphylococcal SCVs were described,
      among them, several pacemaker infections due to SCVs of CoNS auxotrophic to
      hemin. To test the characteristics of SCVs of CoNS, in particular, to study the
      ability of SCVs to form a biofilm on foreign bodies, we generated a stable mutant
      in electron transport by interrupting one of the hemin biosynthetic genes, hemB,
      in Staphylococcus epidermidis. In fact, this mutant displayed a stable SCV
      phenotype with tiny colonies showing strong adhesion to the agar surface. When
      the incubation time was extended to 48 h or a higher inoculum concentration was
      used, the mutant produced biofilm amounts on polystyrene similar to those
      produced by the parent strain. When grown under planktonic conditions, the mutant
      formed markedly larger cell clusters than the parental strain which were
      completely disintegrated by the specific beta-1,6-hexosaminidase dispersin B but
      were resistant to trypsin treatment. In a dot blot assay, the mutant expressed
      larger amounts of polysaccharide intercellular adhesin (PIA) than the parent
      strain. In conclusion, interrupting a hemin biosynthetic gene in S. epidermidis
      resulted in an SCV phenotype. Markedly larger cell clusters and the ability of
      the hemB mutant to form a biofilm are related to the augmented expression of PIA.

PMID- 17449621
TI  - DNA helicase activity of PcrA is not required for the displacement of RecA
      protein from DNA or inhibition of RecA-mediated strand exchange.
AB  - PcrA is a conserved DNA helicase present in all gram-positive bacteria. Bacteria
      lacking PcrA show high levels of recombination. Lethality induced by PcrA
      depletion can be overcome by suppressor mutations in the recombination genes
      recFOR. RecFOR proteins load RecA onto single-stranded DNA during recombination.
      Here we test whether an essential function of PcrA is to interfere with RecA
      mediated DNA recombination in vitro. We demonstrate that PcrA can inhibit the
      RecA-mediated DNA strand exchange reaction in vitro. Furthermore, PcrA displaced
      RecA from RecA nucleoprotein filaments. Interestingly, helicase mutants of PcrA
      also displaced RecA from DNA and inhibited RecA-mediated DNA strand exchange.
      Employing a novel single-pair fluorescence resonance energy transfer-based assay,
      we demonstrate a lengthening of double-stranded DNA upon polymerization of RecA
      and show that PcrA and its helicase mutants can reverse this process. Our results
      show that the displacement of RecA from DNA by PcrA is not dependent on its
      translocase activity. Further, our results show that the helicase activity of
      PcrA, although not essential, might play a facilitatory role in the RecA
      displacement reaction.

PMID- 17449622
TI  - Variability and expression of ankyrin domain genes in Wolbachia variants
      infecting the mosquito Culex pipiens.
AB  - Wolbachia strains are maternally inherited endosymbiotic bacteria that infect
      many arthropod species and have evolved several different ways of manipulating
      their hosts, the most frequent way being cytoplasmic incompatibility (CI). CI
      leads to embryo death in crosses between infected males and uninfected females as
      well as in crosses between individuals infected by incompatible Wolbachia
      strains. The mosquito Culex pipiens exhibits the highest crossing type
      variability reported so far. Our crossing data support the notion that CI might
      be driven by at least two distinct genetic units that control the CI functions
      independently in males and females. Although the molecular basis of CI remains
      unknown, proteins with ankyrin (ANK) domains represent promising candidates since
      they might interact with a wide range of host proteins. Here we searched for
      sequence variability in the 58 ANK genes carried in the genomes of Wolbachia
      variants infecting Culex pipiens. Only five ANK genes were polymorphic in the
      genomes of incompatible Wolbachia variants, and none correlated with the CI
      pattern obtained with 15 mosquito strains (representing 14 Wolbachia variants).
      Further analysis of ANK gene expression evidenced host- and sex-dependent
      variations, which did not improve the correlation. Taken together, these data do
      not support the direct implication of ANK genes in CI determinism.

PMID- 17449623
TI  - Analysis of the first genome of a hyperthermophilic marine virus-like particle,
      PAV1, isolated from Pyrococcus abyssi.
AB  - Only one virus-like particle (VLP) has been reported from hyperthermophilic
      Euryarchaeotes. This VLP, named PAV1, is shaped like a lemon and was isolated
      from a strain of "Pyrococcus abyssi," a deep-sea isolate. Its genome consists of
      a double-stranded circular DNA of 18 kb which is also present at a high copy
      number (60 per chromosome) free within the host cytoplasm but is not integrated
      into the host chromosome. Here, we report the results of complete analysis of the
      PAV1 genome. All the 25 predicted genes, except 3, are located on one DNA strand.
      A transcription map has been made by using a reverse transcription-PCR assay. All
      the identified open reading frames (ORFs) are transcribed. The most significant
      similarities relate to four ORFs. ORF 180a shows 31% identity with ORF 181 of the
      pRT1 plasmid isolated from Pyrococcus sp. strain JT1. ORFs 676 and 678 present
      similarities with a concanavalin A-like lectin/glucanase domain, which could be
      involved in the process of host-virus recognition, and ORF 59 presents
      similarities with the transcriptional regulator CopG. The genome of PAV1 displays
      unique features at the nucleic and proteinic level, indicating that PAV1 should
      be attached at least to a novel genus or virus family.

PMID- 17449624
TI  - pH-dependent association of enolase and glyceraldehyde-3-phosphate dehydrogenase
      of Lactobacillus crispatus with the cell wall and lipoteichoic acids.
AB  - The plasminogen-binding proteins enolase and glyceraldehyde-3-phosphate
      dehydrogenase of Lactobacillus crispatus were localized on the cell surface at pH
      5 but released into the medium at an alkaline pH. These proteins bound to
      lipoteichoic acids at a pH below their isoelectric point. The results indicate
      that lactobacilli rapidly modify their surface properties in response to changes
      in pH.

PMID- 17449625
TI  - Insights into the metabolism of elemental sulfur by the hyperthermophilic
      archaeon Pyrococcus furiosus: characterization of a coenzyme A- dependent NAD(P)H
      sulfur oxidoreductase.
AB  - The hyperthermophilic archaeon Pyrococcus furiosus uses carbohydrates as a carbon
      source and produces acetate, CO2, and H2 as end products. When S(0) is added to a
      growing culture, within 10 min the rate of H2 production rapidly decreases and
      H(2)S is detected. After 1 hour cells contain high NADPH- and coenzyme A
      dependent S(0) reduction activity (0.7 units/mg, 85 degrees C) located in the
      cytoplasm. The enzyme responsible for this activity was purified to
      electrophoretic homogeneity (specific activity, 100 units/mg) and is termed
      NAD(P)H elemental sulfur oxidoreductase (NSR). NSR is a homodimeric flavoprotein
      (M(r), 100,000) and is encoded by PF1186. This designation was previously
      assigned to the gene encoding an enzyme that reduces coenzyme A disulfide, which
      is a side reaction of NSR. Whole-genome DNA microarray and quantitative PCR
      analyses showed that the expression of NSR is up-regulated up to sevenfold within
      10 min of S(0) addition. This primary response to S(0) also involves the up
      regulation (>16-fold) of a 13-gene cluster encoding a membrane-bound
      oxidoreductase (MBX). The cluster encoding MBX is proposed to replace the
      homologous 14-gene cluster that encodes the ferredoxin-oxidizing, H2-evolving
      membrane-bound hydrogenase (MBH), which is down-regulated >12-fold within 10 min
      of S(0) addition. Although an activity for MBX could not be demonstrated, it is
      proposed to conserve energy by oxidizing ferredoxin and reducing NADP, which is
      used by NSR to reduce S(0). A secondary response to S(0) is observed 30 min after
      S(0) addition and includes the up-regulation of genes encoding proteins involved
      in amino acid biosynthesis and iron metabolism, as well as two so-called sulfur
      induced proteins termed SipA and SipB. This novel S(0)-reducing system involving
      NSR and MBX has been found so far only in the heterotrophic Thermococcales and is
      in contrast to the cytochrome- and quinone-based S(0)-reducing system in
      autotrophic archaea and bacteria.

PMID- 17449626
TI  - Enzymology and evolution of the pyruvate pathway to 2-oxobutyrate in
      Methanocaldococcus jannaschii.
AB  - The archaeon Methanocaldococcus jannaschii uses three different 2-oxoacid
      elongation pathways, which extend the chain length of precursors in leucine,
      isoleucine, and coenzyme B biosyntheses. In each of these pathways an aconitase
      type hydrolyase catalyzes an hydroxyacid isomerization reaction. The genome
      sequence of M. jannaschii encodes two homologs of each large and small subunit
      that forms the hydrolyase, but the genes are not cotranscribed. The genes are
      more similar to each other than to previously characterized isopropylmalate
      isomerase or homoaconitase enzyme genes. To identify the functions of these
      homologs, the four combinations of subunits were heterologously expressed in
      Escherichia coli, purified, and reconstituted to generate the iron-sulfur center
      of the holoenzyme. Only the combination of MJ0499 and MJ1277 proteins catalyzed
      isopropylmalate and citramalate isomerization reactions. This pair also catalyzed
      hydration half-reactions using citraconate and maleate. Another broad-specificity
      enzyme, isopropylmalate dehydrogenase (MJ0720), catalyzed the oxidative
      decarboxylation of beta-isopropylmalate, beta-methylmalate, and d-malate.
      Combined with these results, phylogenetic analysis suggests that the pyruvate
      pathway to 2-oxobutyrate (an alternative to threonine dehydratase in isoleucine
      biosynthesis) evolved several times in bacteria and archaea. The enzymes in the
      isopropylmalate pathway of leucine biosynthesis facilitated the evolution of 2
      oxobutyrate biosynthesis through the introduction of a citramalate synthase,
      either by gene recruitment or gene duplication and functional divergence.

PMID- 17449627
TI  - The oxidoreductase DsbA plays a key role in the ability of the Crohn's disease
      associated adherent-invasive Escherichia coli strain LF82 to resist macrophage
      killing.
AB  - Adherent-invasive Escherichia coli (AIEC) isolated from Crohn's disease patients
      is able to adhere to and invade intestinal epithelial cells and to replicate in
      mature phagolysosomes within macrophages. Here, we show that the dsbA gene,
      encoding a periplasmic oxidoreductase, was required for AIEC strain LF82 to
      adhere to intestinal epithelial cells and to survive within macrophages. The LF82
      DeltadsbA mutant did not express flagella and, probably as a consequence of this,
      did not express type 1 pili. The role of DsbA in adhesion is restricted to the
      loss of flagella and type 1 pili, as forced contact between bacteria and cells
      and induced expression of type 1 pili restored the wild-type phenotype. In
      contrast, the dsbA gene is essential for AIEC LF82 bacteria to survive within
      macrophages, irrespective of the loss of flagella and type 1 pilus expression,
      and the survival ability of LF82-DeltadsbA was as low as that of the
      nonpathogenic E. coli K-12, which was efficiently killed by macrophages. We also
      provide evidence that the dsbA gene is needed for LF82 bacteria to grow and
      survive in an acidic and nutrient-poor medium that partly mimics the harsh
      environment of the phagocytic vacuole. In addition, under such stress conditions
      dsbA transcription is highly up-regulated. Finally, the CpxRA signaling pathway
      does not play a role in regulation of dsbA expression in AIEC LF82 bacteria under
      conditions similar to those of mature phagolysosomes.

PMID- 17449628
TI  - Cryo-electron tomography reveals the comparative three-dimensional architecture
      of Prochlorococcus, a globally important marine cyanobacterium.
AB  - In an age of comparative microbial genomics, knowledge of the near-native
      architecture of microorganisms is essential for achieving an integrative
      understanding of physiology and function. We characterized and compared the three
      dimensional architecture of the ecologically important cyanobacterium
      Prochlorococcus in a near-native state using cryo-electron tomography and found
      that closely related strains have diverged substantially in cellular organization
      and structure. By visualizing native, hydrated structures within cells, we
      discovered that the MED4 strain, which possesses one of the smallest genomes
      (1.66 Mbp) of any known photosynthetic organism, has evolved a comparatively
      streamlined cellular architecture. This strain possesses a smaller cell volume,
      an attenuated cell wall, and less extensive intracytoplasmic (photosynthetic)
      membrane system compared to the more deeply branched MIT9313 strain. Comparative
      genomic analyses indicate that differences have evolved in key structural genes,
      including those encoding enzymes involved in cell wall peptidoglycan
      biosynthesis. Although both strains possess carboxysomes that are polygonal and
      cluster in the central cytoplasm, the carboxysomes of MED4 are smaller. A
      streamlined cellular structure could be advantageous to microorganisms thriving
      in the low-nutrient conditions characteristic of large regions of the open ocean
      and thus have consequences for ecological niche differentiation. Through cryo
      electron tomography we visualized, for the first time, the three-dimensional
      structure of the extensive network of photosynthetic lamellae within
      Prochlorococcus and the potential pathways for intracellular and intermembrane
      movement of molecules. Comparative information on the near-native structure of
      microorganisms is an important and necessary component of exploring microbial
      diversity and understanding its consequences for function and ecology.

PMID- 17449629
TI  - Quorum sensing regulates denitrification in Pseudomonas aeruginosa PAO1.
AB  - Anaerobic growth of Pseudomonas aeruginosa PAO1 was affected by quorum sensing.
      Deletion of genes that produce N-acyl-l-homoserine lactone signals resulted in an
      increase in denitrification activity, which was repressed by exogenous signal
      molecules. The effect of the las quorum-sensing system was dependent on the rhl
      quorum-sensing system in regulating denitrification.

PMID- 17449630
TI  - Structure-based functional analysis of the replication protein of plasmid R6K:
      key amino acids at the pi/DNA interface.
AB  - In previous work, we characterized the bases in an iteron of plasmid R6K that are
      important for the binding of pi protein monomers and dimers. Here we investigate
      the following six amino acids of pi, encoded by pir, hypothesized to be important
      for DNA contact: Ser71, Try74, Gly131, Gly211, Arg225, and Arg254.

PMID- 17449631
TI  - Characterization of a novel bile-inducible operon encoding a two-component
      regulatory system in Lactobacillus acidophilus.
AB  - Lactobacillus acidophilus NCFM is an industrially important strain used
      extensively as a probiotic culture. Tolerance of the presence of bile is an
      attribute important to microbial survival in the intestinal tract. A whole-genome
      microarray was employed to examine the effects of bile on the global
      transcriptional profile of this strain, with the intention of elucidating genes
      contributing to bile tolerance. Genes involved in carbohydrate metabolism were
      generally induced, while genes involved in other aspects of cellular growth were
      mostly repressed. A 7-kb eight-gene operon encoding a two-component regulatory
      system (2CRS), a transporter, an oxidoreductase, and four hypothetical proteins
      was significantly upregulated in the presence of bile. Deletion mutations were
      constructed in six genes of the operon. Transcriptional analysis of the 2CRS
      mutants showed that mutation of the histidine protein kinase (HPK) had no effect
      on the induction of the operon, whereas the mutated response regulator (RR)
      showed enhanced induction when the cells were exposed to bile. These results
      indicate that the 2CRS plays a role in bile tolerance and that the operon it
      resides in is negatively controlled by the RR. Mutations in the transporter, the
      HPK, the RR, and a hypothetical protein each resulted in loss of tolerance of
      bile. Mutations in genes encoding another hypothetical protein and a putative
      oxidoreductase resulted in significant increases in bile tolerance. This
      functional analysis showed that the operon encoded proteins involved in both bile
      tolerance and bile sensitivity.

PMID- 17449632
TI  - A Validation and Reliability Study of the Physical Activity and Healthy Food
      Efficacy Scale for Children (PAHFE).
AB  - The purpose of this study was to obtain validity evidence for the Physical
      Activity and Healthy Food Efficacy Scale for Children (PAHFE). Construct validity
      evidence identifies four subscales: Goal-Setting for Physical Activity, Goal
      Setting for Healthy Food Choices, Decision-Making for Physical Activity, and
      Decision-Making for Healthy Food Choices. The scores on each of these subscales
      show a moderate to high degree of internal consistency (0.59 <or= alpha <or=
      0.87). The Decision-Making for Healthy Food Choice subscale and the Decision
      Making for Physical Activity subscale scores show significant convergent validity
      evidence. These results provide support for using this self-efficacy scale to
      measure children's perceived confidence to make decisions about healthy eating
      and physical activity. The PAHFE may be considered to be a useful predictor of
      both physical activity and eating behaviors.

PMID- 17449633
TI  - Interleukin 31 mediates MAP kinase and STAT1/3 activation in intestinal
      epithelial cells and its expression is upregulated in inflammatory bowel disease.
AB  - BACKGROUND/AIM: Interleukin 31 (IL31), primarily expressed in activated
      lymphocytes, signals through a heterodimeric receptor complex consisting of the
      IL31 receptor alpha (IL31Ralpha) and the oncostatin M receptor (OSMR). The aim of
      this study was to analyse IL31 receptor expression, signal transduction, and
      specific biological functions of this cytokine system in intestinal inflammation.
      METHODS: Expression studies were performed by RT-PCR, quantitative PCR, western
      blotting, and immunohistochemistry. Signal transduction was analysed by western
      blotting. Cell proliferation was measured by MTS assays, cell migration by
      restitution assays. RESULTS: Colorectal cancer derived intestinal epithelial cell
      (IEC) lines express both IL31 receptor subunits, while their expression in
      unstimulated primary murine IEC was low. LPS and the proinflammatory cytokines
      TNF-alpha, IL1beta, IFN-gamma, and sodium butyrate stimulation increased IL31,
      IL31Ralpha, and OSMR mRNA expression, while IL31 itself enhanced IL8 expression
      in IEC. IL31 mediates ERK-1/2, Akt, STAT1, and STAT3 activation in IEC resulting
      in enhanced IEC migration. However, at low cell density, IL31 had significant
      antiproliferative capacities (p<0.005). IL31 mRNA expression was not increased in
      the TNFDeltaARE mouse model of ileitis but in inflamed colonic lesions compared
      to non-inflamed tissue in patients with Crohn's disease (CD; average 2.4-fold
      increase) and in patients with ulcerative colitis (UC; average 2.6-fold increase)
      and correlated with the IL-8 expression in these lesions (r = 0.564 for CD; r =
      0.650 for UC; total number of biopsies analysed: n = 88). CONCLUSION: IEC express
      the functional IL31 receptor complex. IL31 modulates cell proliferation and
      migration suggesting a role in the regulation of intestinal barrier function
      particularly in intestinal inflammation.

PMID- 17449634
TI  - Stress-related changes in oesophageal permeability: filling the gaps of GORD?
AB  - Albeit remaining a controversial issue, it has become increasingly recognised
      that psychological stress has a major impact on gut mucosal function and affects
      the course of gastrointestinal disorders. Research during the last decade has
      shown that stress causes barrier dysfunction of the gastrointestinal mucosa by
      mechanisms that mainly involve neuropeptides and mast cells. Moreover,
      accumulating evidence implicates increased permeability as a pathogenic factor in
      gastroesophageal reflux disease (GORD). Recent data demonstrating that
      psychological stress may induce a permeability defect in stratified epithelia,
      including the oesophagus, shed new light on the pathophysiological events leading
      to heartburn and GORD.

PMID- 17449635
TI  - The emergence of simple languages in an experimental coordination game.
AB  - We investigate in a series of laboratory experiments how costs and benefits of
      linguistic communication affect the emergence of simple languages in a
      coordination task when no common language is available in the beginning. The
      experiment involved pairwise computerized communication between 152 subjects
      involved in at least 60 rounds. The subjects had to develop a common code
      referring to items in varying lists of geometrical figures distinguished by up to
      three features. A code had to be made of a limited repertoire of letters. Using
      letters had a cost. We are interested in the question of whether a common code is
      developed, and what enhances its emergence. Furthermore, we explore the emergence
      of compositional, protogrammatical structure in such codes. We compare
      environments that differ in terms of available linguistic resources (number of
      letters available) and in terms of stability of the task environment (variability
      in the set of figures). Our experiments show that a too small repertoire of
      letters causes coordination failures. Cost efficiency and role asymmetry are
      important factors enhancing communicative success. In stable environments,
      grammars do not seem to matter much, and instead efficient arbitrary codes often
      do better. However, in an environment with novelty, compositional grammars offer
      considerable coordination advantages and therefore are more likely to arise.

PMID- 17449636
TI  - More genes underwent positive selection in chimpanzee evolution than in human
      evolution.
AB  - Observations of numerous dramatic and presumably adaptive phenotypic
      modifications during human evolution prompt the common belief that more genes
      have undergone positive Darwinian selection in the human lineage than in the
      chimpanzee lineage since their evolutionary divergence 6-7 million years ago.
      Here, we test this hypothesis by analyzing nearly 14,000 genes of humans and
      chimps. To ensure an accurate and unbiased comparison, we select a proper
      outgroup, avoid sequencing errors, and verify statistical methods. Our results
      show that the number of positively selected genes is substantially smaller in
      humans than in chimps, despite a generally higher nonsynonymous substitution rate
      in humans. These observations are explainable by the reduced efficacy of natural
      selection in humans because of their smaller long-term effective population size
      but refute the anthropocentric view that a grand enhancement in Darwinian
      selection underlies human origins. Although human and chimp positively selected
      genes have different molecular functions and participate in different biological
      processes, the differences do not ostensibly correspond to the widely assumed
      adaptations of these species, suggesting how little is currently known about
      which traits have been under positive selection. Our analysis of the identified
      positively selected genes lends support to the association between human
      Mendelian diseases and past adaptations but provides no evidence for either the
      chromosomal speciation hypothesis or the widespread brain-gene acceleration
      hypothesis of human origins.

PMID- 17449637
TI  - Human relational memory requires time and sleep.
AB  - Relational memory, the flexible ability to generalize across existing stores of
      information, is a fundamental property of human cognition. Little is known,
      however, about how and when this inferential knowledge emerges. Here, we test the
      hypothesis that human relational memory develops during offline time periods.
      Fifty-six participants initially learned five "premise pairs" (A>B, B>C, C>D,
      D>E, and E>F). Unknown to subjects, the pairs contained an embedded hierarchy
      (A>B>C>D>E>F). Following an offline delay of either 20 min, 12 hr (wake or
      sleep), or 24 hr, knowledge of the hierarchy was tested by examining inferential
      judgments for novel "inference pairs" (B>D, C>E, and B>E). Despite all groups
      achieving near-identical premise pair retention after the offline delay (all
      groups, >85%; the building blocks of the hierarchy), a striking dissociation was
      evident in the ability to make relational inference judgments: the 20-min group
      showed no evidence of inferential ability (52%), whereas the 12- and 24-hr groups
      displayed highly significant relational memory developments (inference ability of
      both groups, >75%; P < 0.001). Moreover, if the 12-hr period contained sleep, an
      additional boost to relational memory was seen for the most distant inferential
      judgment (the B>E pair; sleep = 93%, wake = 69%, P = 0.03). Interestingly,
      despite this increase in performance, the sleep benefit was not associated with
      an increase in subjective confidence for these judgments. Together, these
      findings demonstrate that human relational memory develops during offline time
      delays. Furthermore, sleep appears to preferentially facilitate this process by
      enhancing hierarchical memory binding, thereby allowing superior performance for
      the more distant inferential judgments, a benefit that may operate below the
      level of conscious awareness.

PMID- 17449638
TI  - Amphibian and reptile declines over 35 years at La Selva, Costa Rica.
AB  - Amphibians stand at the forefront of a global biodiversity crisis. More than one
      third of amphibian species are globally threatened, and over 120 species have
      likely suffered global extinction since 1980. Most alarmingly, many rapid
      declines and extinctions are occurring in pristine sites lacking obvious adverse
      effects of human activities. The causes of these "enigmatic" declines remain
      highly contested. Still, lack of long-term data on amphibian populations severely
      limits our understanding of the distribution of amphibian declines, and therefore
      the ultimate causes of these declines. Here, we identify a systematic community
      wide decline in populations of terrestrial amphibians at La Selva Biological
      Station, a protected old-growth lowland rainforest in lower Central America. We
      use data collected over 35 years to show that population density of all species
      of terrestrial amphibians has declined by approximately 75% since 1970, and we
      show identical trends for all species of common reptiles. The trends we identify
      are neither consistent with recent emergence of chytridiomycosis nor the climate
      linked epidemic hypothesis, two leading putative causes of enigmatic amphibian
      declines. Instead, our data suggest that declines are due to climate-driven
      reductions in the quantity of standing leaf litter, a critical microhabitat for
      amphibians and reptiles in this assemblage. Our results raise further concerns
      about the global persistence of amphibian populations by identifying widespread
      declines in species and habitats that are not currently recognized as susceptible
      to such risks.

PMID- 17449639
TI  - Mutational reconstructed ferric chelate reductase confers enhanced tolerance in
      rice to iron deficiency in calcareous soil.
AB  - Iron (Fe) deficiency is a worldwide agricultural problem on calcareous soils with
      low-Fe availability due to high soil pH. Rice plants use a well documented
      phytosiderophore-based system (Strategy II) to take up Fe from the soil and also
      possess a direct Fe2+ transport system. Rice plants are extremely susceptible to
      low-Fe supply, however, because of low phytosiderophore secretion and low Fe3+
      reduction activity. A yeast Fe3+ chelate-reductase gene refre1/372, selected for
      better performance at high pH, was fused to the promoter of the Fe-regulated
      transporter, OsIRT1, and introduced into rice plants. The transgene was expressed
      in response to a low-Fe nutritional status in roots of transformants. Transgenic
      rice plants expressing the refre1/372 gene showed higher Fe3+ chelate-reductase
      activity and a higher Fe-uptake rate than vector controls under Fe-deficient
      conditions. Consequently, transgenic rice plants exhibited an enhanced tolerance
      to low-Fe availability and 7.9x the grain yield of nontransformed plants in
      calcareous soils. This report shows that enhancing the Fe3+ chelate-reductase
      activity of rice plants that normally have low endogenous levels confers
      resistance to Fe deficiency.

PMID- 17449640
TI  - Maternal Nanos represses hid/skl-dependent apoptosis to maintain the germ line in
      Drosophila embryos.
AB  - Nanos (Nos) is an evolutionarily conserved protein essential for the survival of
      primordial germ cells. In Drosophila, maternal Nos partitions into pole cells and
      suppresses apoptosis to permit proper germ-line development. However, how this
      critical event is regulated by Nos has remained elusive. Here, we report that Nos
      represses apoptosis of pole cells by suppressing translation of head involution
      defective (hid), a member of the RHG gene family that is required for Caspase
      activation. In addition, we demonstrate that hid acts in concert with another RHG
      gene, sickle (skl), to induce apoptosis. Expression of skl is induced in pole
      cells by maternal tao-1, a ste20-like serine/threonine kinase. Tao-1-dependent
      skl expression is required to potentiate hid activity. However, skl expression is
      largely suppressed in normal pole cells. Once the pole cells lack maternal Nos,
      Tao-1-dependent skl expression is fully activated, suggesting that skl expression
      is also restricted by Nos. These findings provide the first evidence that the
      germ line is maintained through the regulated expression of RHG genes.

PMID- 17449641
TI  - Double-stranded RNA induces galectin-9 in vascular endothelial cells: involvement
      of TLR3, PI3K, and IRF3 pathway.
AB  - Galectin-9 is a member of the galectin family, which induces various biological
      reactions such as chemotaxis of eosinophils and apoptosis of T cells. We
      previously reported that polyinosinic-polycytidylic acid (poly IC), an authentic
      double-stranded RNA (dsRNA), induces the expression of galectin-9 in human
      umbilical vein endothelial cells (HUVECs). In the present study, we addressed the
      possible involvement of two potential receptors for dsRNA, Toll-like receptor
      (TLR) 3 and retinoic acid-inducible gene-I (RIG-I), in the expression of galectin
      9 in HUVECs. Poly IC-induced galectin-9 expression was almost completely
      suppressed by RNA interference (RNAi) against TLR3, but not against RIG-I.
      LY294002, an inhibitor of phosphatidylinositol 3-kinase (PI3K), inhibited the
      induction of galectin-9 by poly IC. RNAi against interferon regulatory factor 3
      (IRF3) also inhibited poly IC-induced galectin-9 expression. We conclude that
      TLR3, PI3K, and IRF3 are involved in the poly IC-induced galectin-9 expression in
      HUVECs.

PMID- 17449642
TI  - Structural views of glycoprotein-fate determination in cells.
AB  - Processing of the N-glycans is coupled with the fates of glycoproteins in cells.
      A series of processing intermediates of high-mannose-type glycans are generated
      by specific glycosidases and thereby express biological signals recognized by
      intracellular lectins operating as molecular chaperones, cargo receptors, and
      ubiquitin ligases. Consequently, these lectins govern the intracellular processes
      of folding, transport, and degradation of the carrier polypeptides. To understand
      the underlying mechanisms of glycoprotein-fate determination, structural
      information on modes of molecular recognition by these lectins and enzymes is
      undoubtedly important. This article overviews our current knowledge of the
      structural basis for quality control of glycoproteins in cells.

PMID- 17449643
TI  - A reevaluation of the key factors that influence tomato fruit softening and
      integrity.
AB  - The softening of fleshy fruits, such as tomato (Solanum lycopersicum), during
      ripening is generally reported to result principally from disassembly of the
      primary cell wall and middle lamella. However, unsuccessful attempts to prolong
      fruit firmness by suppressing the expression of a range of wall-modifying
      proteins in transgenic tomato fruits do not support such a simple model. 'Delayed
      Fruit Deterioration' (DFD) is a previously unreported tomato cultivar that
      provides a unique opportunity to assess the contribution of wall metabolism to
      fruit firmness, since DFD fruits exhibit minimal softening but undergo otherwise
      normal ripening, unlike all known nonsoftening tomato mutants reported to date.
      Wall disassembly, reduced intercellular adhesion, and the expression of genes
      associated with wall degradation were similar in DFD fruit and those of the
      normally softening 'Ailsa Craig'. However, ripening DFD fruit showed minimal
      transpirational water loss and substantially elevated cellular turgor. This
      allowed an evaluation of the relative contribution and timing of wall disassembly
      and water loss to fruit softening, which suggested that both processes have a
      critical influence. Biochemical and biomechanical analyses identified several
      unusual features of DFD cuticles and the data indicate that, as with wall
      metabolism, changes in cuticle composition and architecture are an integral and
      regulated part of the ripening program. A model is proposed in which the cuticle
      affects the softening of intact tomato fruit both directly, by providing a
      physical support, and indirectly, by regulating water status.

PMID- 17449644
TI  - Deficiency in phosphatidylserine decarboxylase activity in the psd1 psd2 psd3
      triple mutant of Arabidopsis affects phosphatidylethanolamine accumulation in
      mitochondria.
AB  - Phosphatidylserine (PS) decarboxylase is involved in the synthesis of the
      abundant phospholipid phosphatidylethanolamine (PE), particularly in
      mitochondria, in many organisms, including yeast (Saccharomyces cerevisiae) and
      animals. Arabidopsis (Arabidopsis thaliana) contains three genes with sequence
      similarity to PS decarboxylases, and the respective gene products were
      functionally characterized after heterologous expression in yeast and Escherichia
      coli. While the PSD1 protein localizes to mitochondria, PSD2 and PSD3 are found
      in the endomembrane system. To study the role of PSD genes in plant phospholipid
      metabolism, Arabidopsis insertional mutants for psd1, psd2, and psd3 were
      obtained. The single mutants were decreased in PS decarboxylase activity to
      various extents, but mutant plants showed no obvious growth or morphological
      phenotype. A triple mutant, psd1 psd2 psd3, was generated that was totally devoid
      of PS decarboxylase activity. While the phospholipid composition in whole leaves
      was unchanged, the PE content in isolated mitochondria of psd1 psd2 psd3 was
      decreased. Therefore, the predominant proportion of PE in Arabidopsis is
      synthesized by alternative pathways, but a significant amount of mitochondrial PE
      is derived from the PS decarboxylase reaction. These results imply that, similar
      to yeast and animal cells, a specific phospholipid transfer from the endoplasmic
      reticulum to mitochondria exists in plants.

PMID- 17449645
TI  - Mutation of E1-CONJUGATING ENZYME-RELATED1 decreases RELATED TO UBIQUITIN
      conjugation and alters auxin response and development.
AB  - The ubiquitin-like protein RELATED TO UBIQUITIN (RUB) is conjugated to CULLIN
      (CUL) proteins to modulate the activity of Skp1-Cullin-F-box (SCF) ubiquitylation
      complexes. RUB conjugation to specific target proteins is necessary for the
      development of many organisms, including Arabidopsis (Arabidopsis thaliana).
      Here, we report the isolation and characterization of e1-conjugating enzyme
      related1-1 (ecr1-1), an Arabidopsis mutant compromised in RUB conjugation. The
      ecr1-1 mutation causes a missense change located two amino acid residues from the
      catalytic site cysteine, which normally functions to form a thioester bond with
      activated RUB. A higher ratio of unmodified CUL1 relative to CUL1-RUB is present
      in ecr1-1 compared to wild type, suggesting that the mutation reduces ECR1
      function. The ecr1-1 mutant is resistant to the auxin-like compound indole-3
      propionic acid, produces fewer lateral roots than wild type, displays reduced
      adult height, and stabilizes a reporter fusion protein that is degraded in
      response to auxin, suggesting reduced auxin signaling in the mutant. In addition,
      ecr1-1 hypocotyls fail to elongate normally when seedlings are grown in darkness,
      a phenotype shared with certain other RUB conjugation mutants that is not general
      to auxin-response mutants. The suite of ecr1-1 molecular and morphological
      phenotypes reflects roles for RUB conjugation in many aspects of plant growth and
      development. Certain ecr1-1 elongation defects are restored by treatment with the
      ethylene-response inhibitor silver nitrate, suggesting that the short ecr1-1 root
      and hypocotyl result from aberrant ethylene accumulation. Further, silver nitrate
      supplementation in combination with various auxins and auxin-like compounds
      reveals that members of this growth regulator family may differentially rely on
      ethylene signaling to inhibit root growth.

PMID- 17449646
TI  - White leaf sectors in yellow variegated2 are formed by viable cells with
      undifferentiated plastids.
AB  - The yellow variegated2 (var2) is one of the best-characterized Arabidopsis
      (Arabidopsis thaliana) mutants showing leaf variegation. Leaf variegation of var2
      results from the loss of an ATP-dependent metalloprotease, FtsH2, which is a
      major component of the FtsH heterocomplex in thylakoid membranes. While the
      functional role of FtsH2 in protein quality control has been extensively studied,
      the physiological state of plastids in white tissues of the var2 is not well
      characterized. Here we show that the white tissue in var2 is neither the result
      of photobleaching nor enhanced senescence. Visualization of plastids by plastid
      targeted green fluorescent protein revealed that plastids in the white sector are
      distinct and have undifferentiated characteristics. The plastids are also
      distinct in that they contain large nucleoids, a complex structure of plastid DNA
      and proteins, that are typically found in undifferentiated plastids. Comparative
      analyses of protein profiles from green and white tissues suggested that the
      difference was observed in the proteins related to photosynthesis but not due to
      proteins of other organelles. Thus, cells in the white tissue are viable and
      their defect is limited to plastid function. The plastid accumulates normal
      levels of chloroplast transcripts, whereas a substantial repression of nuclear
      encoded photosynthetic genes was evident in the white sector. Based upon these
      results, we inferred that the white sectors in var2 are made by viable cells that
      have plastids arrested in thylakoid formation. A proposed model to form the
      variegated sector in var2 is provided.

PMID- 17449647
TI  - Barley MLO modulates actin-dependent and actin-independent antifungal defense
      pathways at the cell periphery.
AB  - Cell polarization is a crucial process during plant development, as well as in
      plant-microbe interactions, and is frequently associated with extensive
      cytoskeletal rearrangements. In interactions of plants with inappropriate fungal
      pathogens (so-called non-host interactions), the actin cytoskeleton is thought to
      contribute to the establishment of effective barriers at the cell periphery
      against fungal ingress. Here, we impeded actin cytoskeleton function in various
      types of disease resistance using pharmacological inhibitors and genetic
      interference via ectopic expression of an actin-depolymerizing factor-encoding
      gene, ADF. We demonstrate that barley (Hordeum vulgare) epidermal cells require
      actin cytoskeleton function for basal defense to the appropriate powdery mildew
      pathogen Blumeria graminis f. sp. hordei and for mlo-mediated resistance at the
      cell wall, but not for several tested race-specific immune responses. Analysis of
      non-host resistance to two tested inappropriate powdery mildews, Erysiphe pisi
      and B. graminis f. sp. tritici, revealed the existence of actin-dependent and
      actin-independent resistance pathways acting at the cell periphery. These
      pathways act synergistically and appear to be under negative control by the
      plasma membrane-resident MLO protein.

PMID- 17449648
TI  - barren inflorescence2 Encodes a co-ortholog of the PINOID serine/threonine kinase
      and is required for organogenesis during inflorescence and vegetative development
      in maize.
AB  - Organogenesis in plants is controlled by meristems. Axillary meristems, which
      give rise to branches and flowers, play a critical role in plant architecture and
      reproduction. Maize (Zea mays) and rice (Oryza sativa) have additional types of
      axillary meristems in the inflorescence compared to Arabidopsis (Arabidopsis
      thaliana) and thus provide an excellent model system to study axillary meristem
      initiation. Previously, we characterized the barren inflorescence2 (bif2) mutant
      in maize and showed that bif2 plays a key role in axillary meristem and lateral
      primordia initiation in the inflorescence. In this article, we cloned bif2 by
      transposon tagging. Isolation of bif2-like genes from seven other grasses, along
      with phylogenetic analysis, showed that bif2 is a co-ortholog of PINOID (PID),
      which regulates auxin transport in Arabidopsis. Expression analysis showed that
      bif2 is expressed in all axillary meristems and lateral primordia during
      inflorescence and vegetative development in maize and rice. Further phenotypic
      analysis of bif2 mutants in maize illustrates additional roles of bif2 during
      vegetative development. We propose that bif2/PID sequence and expression are
      conserved between grasses and Arabidopsis, attesting to the important role they
      play in development. We provide further support that bif2, and by analogy PID, is
      required for initiation of both axillary meristems and lateral primordia.

PMID- 17449649
TI  - Molecular evolution of lysin motif-type receptor-like kinases in plants.
AB  - The lysin motif (LysM) domain is an ancient and ubiquitous protein module that
      binds peptidoglycan and structurally related molecules. A genomic survey in a
      large number of species spanning all kingdoms reveals that the combination of
      LysM and receptor kinase domains is present exclusively in plants. However, the
      particular biological functions and molecular evolution of this gene family
      remain largely unknown. We show that LysM domains in plant LysM proteins are
      highly diversified and that a minimum of six distinct types of LysM motifs exist
      in plant LysM kinase proteins and five additional types of LysM motifs exist in
      nonkinase plant LysM proteins. Further, motif similarities suggest that plant
      LysM motifs are ancient. Although phylogenetic signals are not sufficient to
      resolve the earliest relationships, plant LysM motifs may have arisen through
      common ancestry with LysM motifs in other kingdoms. Within plants, the gene
      family has evolved through local and segmental duplications. The family has
      undergone further duplication and diversification in legumes, where some LysM
      kinase genes function as receptors for bacterial nodulation factor. Two pairs of
      homeologous regions were identified in soybean (Glycine max) based on
      microsynteny and fluorescence in situ hybridization. Expression data show that
      most plant LysM kinase genes are expressed predominantly in the root and that
      orthologous LysM kinase genes share similar tissue expression patterns. We also
      examined synteny around plant LysM kinase genes to help reconstruct scenarios for
      the evolution of this important gene family.

PMID- 17449650
TI  - Developmental genes have pleiotropic effects on plant morphology and source
      capacity, eventually impacting on seed protein content and productivity in pea.
AB  - Increasing pea (Pisum sativum) seed nutritional value and particularly seed
      protein content, while maintaining yield, is an important challenge for further
      development of this crop. Seed protein content and yield are complex and unstable
      traits, integrating all the processes occurring during the plant life cycle.
      During filling, seeds are the main sink to which assimilates are preferentially
      allocated at the expense of vegetative organs. Nitrogen seed demand is satisfied
      partly by nitrogen acquired by the roots, but also by nitrogen remobilized from
      vegetative organs. In this study, we evaluated the respective roles of nitrogen
      source capacity and sink strength in the genetic variability of seed protein
      content and yield. We showed in eight genotypes of diverse origins that both the
      maximal rate of nitrogen accumulation in the seeds and nitrogen source capacity
      varied among genotypes. Then, to identify the genetic factors responsible for
      seed protein content and yield variation, we searched for quantitative trait loci
      (QTL) for seed traits and for indicators of sink strength and source nitrogen
      capacity. We detected 261 QTL across five environments for all traits measured.
      Most QTL for seed and plant traits mapped in clusters, raising the possibility of
      common underlying processes and candidate genes. In most environments, the genes
      Le and Afila, which control internode length and the switch between leaflets and
      tendrils, respectively, determined plant nitrogen status. Depending on the
      environment, these genes were linked to QTL of seed protein content and yield,
      suggesting that source-sink adjustments depend on growing conditions.

PMID- 17449652
TI  - Gene targeting by homologous recombination as a biotechnological tool for rice
      functional genomics.
AB  - The modification of an endogenous gene into a designed sequence by homologous
      recombination, termed gene targeting (GT), has broad implications for basic and
      applied research. Rice (Oryza sativa), with a sequenced genome of 389 Mb, is one
      of the most important crops and a model plant for cereals, and the single-copy
      gene Waxy on chromosome 6 has been modified with a frequency of 1% per surviving
      callus by GT using a strong positive-negative selection. Because the strategy is
      independent of gene-specific selection or screening, it is in principle
      applicable to any gene. However, a gene in the multigene family or a gene
      carrying repetitive sequences may preclude efficient homologous recombination
      promoted GT due to the occurrence of ectopic recombination. Here, we describe an
      improved GT procedure whereby we obtained nine independent transformed calli
      having the alcohol dehydrogenase2 (Adh2) gene modified with a frequency of
      approximately 2% per surviving callus and subsequently isolated eight fertile
      transgenic plants without the concomitant occurrence of undesirable ectopic
      events, even though the rice genome carries four Adh genes, including a newly
      characterized Adh3 gene, and a copy of highly repetitive retroelements is present
      adjacent to the Adh2 gene. The results indicate that GT using a strong positive
      negative selection can be widely applicable to functional genomics in rice and
      presumably in other higher plants.

PMID- 17449651
TI  - Phosphorus stress in common bean: root transcript and metabolic responses.
AB  - Phosphorus (P) is an essential element for plant growth. Crop production of
      common bean (Phaseolus vulgaris), the most important legume for human
      consumption, is often limited by low P in the soil. Functional genomics were used
      to investigate global gene expression and metabolic responses of bean plants
      grown under P-deficient and P-sufficient conditions. P-deficient plants showed
      enhanced root to shoot ratio accompanied by reduced leaf area and net
      photosynthesis rates. Transcript profiling was performed through hybridization of
      nylon filter arrays spotted with cDNAs of 2,212 unigenes from a P deficiency root
      cDNA library. A total of 126 genes, representing different functional categories,
      showed significant differential expression in response to P: 62% of these were
      induced in P-deficient roots. A set of 372 bean transcription factor (TF) genes,
      coding for proteins with Inter-Pro domains characteristic or diagnostic for TF,
      were identified from The Institute of Genomic Research/Dana Farber Cancer
      Institute Common Bean Gene Index. Using real-time reverse transcription
      polymerase chain reaction analysis, 17 TF genes were differentially expressed in
      P-deficient roots; four TF genes, including MYB TFs, were induced. Nonbiased
      metabolite profiling was used to assess the degree to which changes in gene
      expression in P-deficient roots affect overall metabolism. Stress-related
      metabolites such as polyols accumulated in P-deficient roots as well as sugars,
      which are known to be essential for P stress gene induction. Candidate genes have
      been identified that may contribute to root adaptation to P deficiency and be
      useful for improvement of common bean.

PMID- 17449653
TI  - Intact plant magnetic resonance imaging to study dynamics in long-distance sap
      flow and flow-conducting surface area.
AB  - Due to the fragile pressure gradients present in the xylem and phloem, methods to
      study sap flow must be minimally invasive. Magnetic resonance imaging (MRI) meets
      this condition. A dedicated MRI method to study sap flow has been applied to
      quantify long-distance xylem flow and hydraulics in an intact cucumber (Cucumis
      sativus) plant. The accuracy of this MRI method to quantify sap flow and
      effective flow-conducting area is demonstrated by measuring the flow
      characteristics of the water in a virtual slice through the stem and comparing
      the results with water uptake data and microscopy. The in-plane image resolution
      of 120 x 120 microm was high enough to distinguish large individual xylem
      vessels. Cooling the roots of the plant severely inhibited water uptake by the
      roots and increased the hydraulic resistance of the plant stem. This increase is
      at least partially due to the formation of embolisms in the xylem vessels.
      Refilling the larger vessels seems to be a lengthy process. Refilling started in
      the night after root cooling and continued while neighboring vessels at a
      distance of not more than 0.4 mm transported an equal amount of water as before
      root cooling. Relative differences in volume flow in different vascular bundles
      suggest differences in xylem tension for different vascular bundles. The amount
      of data and detail that are presented for this single plant demonstrates new
      possibilities for using MRI in studying the dynamics of long-distance transport
      in plants.

PMID- 17449654
TI  - Carbohydrate metabolism in the Toxoplasma gondii apicoplast: localization of
      three glycolytic isoenzymes, the single pyruvate dehydrogenase complex, and a
      plastid phosphate translocator.
AB  - Many apicomplexan parasites, such as Toxoplasma gondii and Plasmodium species,
      possess a nonphotosynthetic plastid, referred to as the apicoplast, which is
      essential for the parasites' viability and displays characteristics similar to
      those of nongreen plastids in plants. In this study, we localized several key
      enzymes of the carbohydrate metabolism of T. gondii to either the apicoplast or
      the cytosol by engineering parasites which express epitope-tagged fusion
      proteins. The cytosol contains a complete set of enzymes for glycolysis, which
      should enable the parasite to metabolize imported glucose into pyruvate. All the
      glycolytic enzymes, from phosphofructokinase up to pyruvate kinase, are present
      in the T. gondii genome, as duplicates and isoforms of triose phosphate
      isomerase, phosphoglycerate kinase, and pyruvate kinase were found to localize to
      the apicoplast. The mRNA expression levels of all genes with glycolytic products
      were compared between tachyzoites and bradyzoites; however, a strict bradyzoite
      specific expression pattern was observed only for enolase I. The T. gondii genome
      encodes a single pyruvate dehydrogenase complex, which was located in the
      apicoplast and absent in the mitochondrion, as shown by targeting of epitope
      tagged fusion proteins and by immunolocalization of the native pyruvate
      dehydrogenase complex. The exchange of metabolites between the cytosol and the
      apicoplast is likely to be mediated by a phosphate translocator which was
      localized to the apicoplast. Based on these localization studies, a model is
      proposed that explains the supply of the apicoplast with ATP and the reduction
      power, as well as the exchange of metabolites between the cytosol and the
      apicoplast.

PMID- 17449655
TI  - Transcriptional profiling of cross pathway control in Neurospora crassa and
      comparative analysis of the Gcn4 and CPC1 regulons.
AB  - Identifying and characterizing transcriptional regulatory networks is important
      for guiding experimental tests on gene function. The characterization of
      regulatory networks allows comparisons among both closely and distantly related
      species, providing insight into network evolution, which is predicted to
      correlate with the adaptation of different species to particular environmental
      niches. One of the most intensely studied regulatory factors in the yeast
      Saccharomyces cerevisiae is the bZIP transcription factor Gcn4p. Gcn4p is
      essential for a global transcriptional response when S. cerevisiae experiences
      amino acid starvation. In the filamentous ascomycete Neurospora crassa, the
      ortholog of GCN4 is called the cross pathway control-1 (cpc-1) gene; it is
      required for the ability of N. crassa to induce a number of amino acid
      biosynthetic genes in response to amino acid starvation. Here, we deciphered the
      CPC1 regulon by profiling transcription in wild-type and cpc-1 mutant strains
      with full-genome N. crassa 70-mer oligonucleotide microarrays. We observed that
      at least 443 genes were direct or indirect CPC1 targets; these included 67 amino
      acid biosynthetic genes, 16 tRNA synthetase genes, and 13 vitamin-related genes.
      Comparison among the N. crassa CPC1 transcriptional profiling data set and the
      Gcn4/CaGcn4 data sets from S. cerevisiae and Candida albicans revealed a
      conserved regulon of 32 genes, 10 of which are predicted to be directly regulated
      by Gcn4p/CPC1. The 32-gene conserved regulon comprises mostly amino acid
      biosynthetic genes. The comparison of regulatory networks in species with clear
      orthology among genes sheds light on how gene interaction networks evolve.

PMID- 17449656
TI  - PfGCN5-mediated histone H3 acetylation plays a key role in gene expression in
      Plasmodium falciparum.
AB  - Histone acetylation, regulated by the opposing actions of histone
      acetyltransferases (HATs) and deacetylases, is an important epigenetic mechanism
      in eukaryotic transcription. Although an acetyltransferase (PfGCN5) has been
      shown to preferentially acetylate histone H3 at K9 and K14 in Plasmodium
      falciparum, the scale of histone acetylation in the parasite genome and its role
      in transcriptional activation are essentially unknown. Using chromatin
      immunoprecipitation (ChIP) and DNA microarray, we mapped the global distribution
      of PfGCN5, histone H3K9 acetylation (H3K9ac) and trimethylation (H3K9m3) in the
      P. falciparum genome. While the chromosomal distributions of H3K9ac and PfGCN5
      were similar, they are radically different from that of H3K9m3. In addition,
      there was a positive, though weak correlation between relative occupancy of
      H3K9ac on individual genes and the levels of gene expression, which was inversely
      proportional to the distance of array elements from the putative translational
      start codons. In contrast, H3K9m3 was negatively correlated with gene expression.
      Furthermore, detailed mapping of H3K9ac for selected genes using ChIP and real
      time PCR in three erythrocytic stages detected stage-specific peak H3K9ac
      enrichment at the putative transcriptional initiation sites, corresponding to
      stage-specific expression of these genes. These data are consistent with H3K9ac
      and H3K9m3 as epigenetic markers of active and silent genes, respectively. We
      also showed that treatment with a PfGCN5 inhibitor led to reduced promoter H3K9ac
      and gene expression. Collectively, these results suggest that PfGCN5 is recruited
      to the promoter regions of genes to mediate histone acetylation and activate gene
      expression in P. falciparum.

PMID- 17449657
TI  - Cryptococcus neoformans mates on pigeon guano: implications for the realized
      ecological niche and globalization.
AB  - The ecological niche that a species can occupy is determined by its resource
      requirements and the physical conditions necessary for survival. The niche to
      which an organism is most highly adapted is the realized niche, whereas the
      complete range of habitats that an organism can occupy represents the fundamental
      niche. The growth and development of Cryptococcus neoformans and Cryptococcus
      gattii on pigeon guano were examined to determine whether these two species
      occupy the same or different ecological niches. C. neoformans is a cosmopolitan
      pathogenic yeast that infects predominantly immunocompromised individuals, exists
      in two varieties (grubii [serotype A] and neoformans [serotype D]), and is
      commonly isolated from pigeon guano worldwide. By contrast, C. gattii often
      infects immunocompetent individuals and is associated with geographically
      restricted environments, most notably, eucalyptus trees. Pigeon guano supported
      the growth of both species, and a brown pigment related to melanin, a key
      virulence factor, was produced. C. neoformans exhibited prolific mating on pigeon
      guano, whereas C. gattii did not. The observations that C. neoformans completes
      the life cycle on pigeon guano but that C. gattii does not indicates that pigeon
      guano could represent the realized ecological niche for C. neoformans. Because C.
      gattii grows on pigeon guano but cannot sexually reproduce, pigeon guano
      represents a fundamental but not a realized niche for C. gattii. Based on these
      studies, we hypothesize that an ancestral Cryptococcus strain gained the ability
      to sexually reproduce in pigeon guano and then swept the globe.

PMID- 17449659
TI  - Effect of membrane microheterogeneity and domain size on fluorescence resonance
      energy transfer.
AB  - Studies of multicomponent membranes suggest lateral inhomogeneity in the form of
      membrane domains, but the size of small (nanoscale) domains in situ cannot be
      determined with current techniques. In this article, we present a model that
      enables extraction of membrane domain size from time-resolved fluorescence
      resonance energy transfer (FRET) data. We expand upon a classic approach to the
      infinite phase separation limit and formulate a model that accounts for the
      presence of disklike domains of finite dimensions within a two-dimensional
      infinite planar bilayer. The model was tested against off-lattice Monte Carlo
      calculations of a model membrane in the liquid-disordered (l(d)) and liquid
      ordered (l(o)) coexistence regime. Simulated domain size was varied from 5 to 50
      nm, and two fluorophores, preferentially partitioning into opposite phases, were
      randomly mixed to obtain the simulated time-resolved FRET data. The Monte Carlo
      data show clear differences in the efficiency of energy transfer as a function of
      domain size. The model fit of the data yielded good agreement for the domain
      size, especially in cases where the domain diameter is <20 nm. Thus, data
      analysis using the proposed model enables measurement of nanoscale membrane
      domains using time-resolved FRET.

PMID- 17449660
TI  - Phase behavior of an intact monoclonal antibody.
AB  - Understanding protein phase behavior is important for purification, storage, and
      stable formulation of protein drugs in the biopharmaceutical industry.
      Glycoproteins, such as monoclonal antibodies (MAbs) are the most abundant
      biopharmaceuticals and probably the most difficult to crystallize among water
      soluble proteins. This study explores the possibility of correlating osmotic
      second virial coefficient (B(22)) with the phase behavior of an intact MAb, which
      has so far proved impossible to crystallize. The phase diagram of the MAb is
      presented as a function of the concentration of different classes of
      precipitants, i.e., NaCl, (NH4)2SO4, and polyethylene glycol. All these
      precipitants show a similar behavior of decreasing solubility with increasing
      precipitant concentration. B(22) values were also measured as a function of the
      concentration of the different precipitants by self-interaction chromatography
      and correlated with the phase diagrams. Correlating phase diagrams with B(22)
      data provides useful information not only for a fundamental understanding of the
      phase behavior of MAbs, but also for understanding the reason why certain
      proteins are extremely difficult to crystallize. The scaling of the phase diagram
      in B(22) units also supports the existence of a universal phase diagram of a
      complex glycoprotein when it is recast in a protein interaction parameter.

PMID- 17449661
TI  - Energy landscape of chelated uranyl: antibody interactions by dynamic force
      spectroscopy.
AB  - We used dynamic force spectroscopy (DFS) to explore the energy landscape of
      interactions between a chelated uranyl compound and a monoclonal antibody raised
      against the uranyl-dicarboxy-phenanthroline complex. We estimated the potential
      energy barrier widths and the relevant thermodynamic rate constants along the
      dissociation coordinate. Using atomic force microscopy, four different
      experimental setups with or without the uranyl ion in the chelate ligand, we have
      distinguished specific and nonspecific binding in the binding affinity of the
      uranyl compound to the antibody. The force loading rates for our system were
      measured from 15 to 26,400 pN/s. The results showed two regimes in the plot of
      the most probable unbinding force versus the logarithm of the loading rate,
      revealing the presence of two (at least) activation barriers. Analyses of DFS
      suggest parallel multivalent binding present in either regime. We have also built
      a molecular model for the variable fragment of the antibody and used
      computational graphics to dock the chelated uranyl ion into the binding pocket.
      The structural analysis led us to hypothesize that the two regimes originate from
      two interaction modes: the first one corresponds to an energy barrier with a very
      narrow width of 0.5 +/- 0.2 A, inferring dissociation of the uranyl ion from its
      first coordination shell (Asp residue); the second one with a broader energy
      barrier width (3.9 +/- 0.3 A) infers the entire chelate compound dissociated from
      the antibody. Our study highlights the sensitivity of DFS experiments to dissect
      protein-metal compound interactions.

PMID- 17449658
TI  - Transcriptome analysis in response to heat shock and cadmium in the aquatic
      fungus Blastocladiella emersonii.
AB  - The global transcriptional response of the chytridiomycete Blastocladiella
      emersonii to environmental stress conditions was explored by sequencing a large
      number of expressed sequence tags (ESTs) from three distinct cDNA libraries,
      constructed with mRNA extracted from cells exposed to heat shock and different
      concentrations of cadmium chloride. A total of 6,350 high-quality EST sequences
      were obtained and assembled into 2,326 putative unigenes, 51% of them not
      previously described in B. emersonii. To approximately 59% of the unigenes it was
      possible to assign an orthologue in another organism, whereas 41% of them
      remained without a putative identification, with transcripts related to protein
      folding and antioxidant activity being highly enriched in the stress libraries. A
      microarray chip was constructed encompassing 3,773 distinct ESTs from the B.
      emersonii transcriptome presently available, which correspond to a wide range of
      biological processes. Global gene expression analysis of B. emersonii cells
      exposed to stress conditions revealed a large number of differentially expressed
      genes: 122 up- and 60 downregulated genes during heat shock and 189 up- and 110
      downregulated genes during exposure to cadmium. The main functional categories
      represented among the upregulated genes were protein folding and proteolysis,
      proteins with antioxidant properties, and cellular transport. Interestingly, in
      response to cadmium stress, B. emersonii cells induced genes encoding six
      different glutathione S-transferases and six distinct metacaspases, as well as
      genes coding for several proteins of sulfur amino acid metabolism, indicating
      that cadmium causes oxidative stress and apoptosis in this fungus. All sequences
      described in this study have been submitted to the GenBank EST section with the
      accession numbers EE 730389 to EE 736848.

PMID- 17449662
TI  - Rapid membrane fusion of individual virus particles with supported lipid
      bilayers.
AB  - Many enveloped viruses employ low-pH-triggered membrane fusion during cell
      penetration. Solution-based in vitro assays in which viruses fuse with liposomes
      have provided much of our current biochemical understanding of low-pH-triggered
      viral membrane fusion. Here, we extend this in vitro approach by introducing a
      fluorescence assay using single particle tracking to observe lipid mixing between
      individual virus particles (influenza or Sindbis) and supported lipid bilayers.
      Our single-particle experiments reproduce many of the observations of the
      solution assays. The single-particle approach naturally separates the processes
      of membrane binding and membrane fusion and therefore allows measurement of
      details that are not available in the bulk assays. We find that the dynamics of
      lipid mixing during individual Sindbis fusion events is faster than 30 ms.
      Although neither virus binds membranes at neutral pH, under acidic conditions,
      the delay between membrane binding and lipid mixing is less than half a second
      for nearly all virus-membrane combinations. The delay between binding and lipid
      mixing lengthened only for Sindbis virus at the lowest pH in a cholesterol
      dependent manner, highlighting the complex interaction between lipids, virus
      proteins, and buffer conditions in membrane fusion.

PMID- 17449663
TI  - A hybrid model for erythrocyte membrane: a single unit of protein network coupled
      with lipid bilayer.
AB  - To investigate the nanomechanics of the erythrocyte membrane we developed a
      hybrid model that couples the actin-spectrin network to the lipid bilayer. This
      model features a Fourier space Brownian dynamics model of the bilayer, a Brownian
      dynamics model of the actin protofilament, and a modified wormlike-chain model of
      the spectrin (including a cable-dynamics model to predict the oscillation in
      tension). This model enables us to predict the nanomechanics of single or
      multiple units of the protein network, the lipid bilayer, and the effect of their
      interactions. The present work is focused on the attitude of the actin
      protofilament at the equilibrium states coupled with the elevations of the lipid
      bilayer through their primary linkage at the suspension complex in deformations.
      Two different actin-spectrin junctions are considered at the junctional complex.
      With a point-attachment junction, large pitch angles and bifurcation of yaw
      angles are predicted. Thermal fluctuations at bifurcation may lead to mode
      switching, which may affect the network and the physiological performance of the
      membrane. In contrast, with a wrap-around junction, pitch angles remain small,
      and the occurrence of bifurcation is greatly reduced. These simulations suggest
      the importance of three-dimensional molecular junctions and the lipid
      bilayer/protein network coupling on cell membrane mechanics.

PMID- 17449664
TI  - Water transport in aquaporins: osmotic permeability matrix analysis of molecular
      dynamics simulations.
AB  - Single-channel osmotic water permeability (p(f)) is a key quantity for
      investigating the transport capability of the water channel protein, aquaporin.
      However, the direct connection between the single scalar quantity p(f) and the
      channel structure remains unclear. In this study, based on molecular dynamics
      simulations, we propose a p(f)-matrix method, in which p(f) is decomposed into
      contributions from each local region of the channel. Diagonal elements of the
      p(f) matrix are equivalent to the local permeability at each region of the
      channel, and off-diagonal elements represent correlated motions of water
      molecules in different regions. Averaging both diagonal and off-diagonal elements
      of the p(f) matrix recovers p(f) for the entire channel; this implies that
      correlated motions between distantly-separated water molecules, as well as
      adjacent water molecules, influence the osmotic permeability. The p(f) matrices
      from molecular dynamics simulations of five aquaporins (AQP0, AQP1, AQP4, AqpZ,
      and GlpF) indicated that the reduction in the water correlation across the Asn
      Pro-Ala region, and the small local permeability around the ar/R region,
      characterize the transport efficiency of water. These structural determinants in
      water permeation were confirmed in molecular dynamics simulations of three
      mutants of AqpZ, which mimic AQP1.

PMID- 17449665
TI  - The stoichiometry of P2X2/6 receptor heteromers depends on relative subunit
      expression levels.
AB  - Fast synaptic transmission involves the operation of ionotropic receptors, which
      are often composed of at least two types of subunit. We have developed a method,
      based on atomic force microscopy imaging to determine the stoichiometry and
      subunit arrangement within ionotropic receptors. We showed recently that the
      P2X(2) receptor for ATP is expressed as a trimer but that the P2X(6) subunit is
      unable to oligomerize. In this study we addressed the subunit stoichiometry of
      heteromers containing both P2X(2) and P2X(6) subunits. We transfected tsA 201
      cells with both P2X(2) and P2X(6) subunits, bearing different epitope tags. We
      manipulated the transfection conditions so that either P2X(2) or P2X(6) was the
      predominant subunit expressed. By atomic force microscopy imaging of isolated
      receptors decorated with antiepitope antibodies, we demonstrate that when
      expression of the P2X(2) subunit predominates, the receptors contain primarily 2
      x P2X(2) subunits and 1 x P2X(6) subunit. In contrast, when the P2X(6) subunit
      predominates, the subunit stoichiometry of the receptors is reversed. Our results
      show that the composition of P2X receptor heteromers is plastic and dependent on
      the relative subunit expression levels. We suggest that this property of receptor
      assembly might introduce an additional layer of subtlety into P2X receptor
      signaling.

PMID- 17449666
TI  - The role of backscattering in SHG tissue imaging.
AB  - We investigate the properties of second-harmonic generation (SHG) tissue imaging
      for the functional biological unit fascia, skeletal muscle, and tendon. Fascia
      and Achilles tendon primarily consist of similar collagen type I arrays that can
      be imaged using SHG microscopy. For muscle, it is the myosin molecules
      represented within the A bands. For fascia and tendon tissue samples, we observe,
      in addition to a stronger signal in forward images, vastly different features for
      the backward versus the forward images. In vivo as well as intact ex vivo thick
      tissue imaging requires backward detection. The obtained image is a result of the
      direct backward components plus a certain fraction of the forward components that
      are redirected (backscattered) toward the objective as they propagate within the
      tissue block. As the forward and the backward images are significantly different
      from each other for the imaged collagen type I tissue, it is crucial to determine
      the fraction of the forward signal that contributes to the overall backward
      signal. For intact ex vivo SHG imaging of Achilles tendon, we observe a
      significant contribution of forward features in the resulting image. For fascia,
      the connective tissue immediately surrounding muscle, we only observe backward
      features, due to low backscattering in muscle.

PMID- 17449667
TI  - Spectrally resolved multiphoton imaging of in vivo and excised mouse skin
      tissues.
AB  - The deep tissue penetration and submicron spatial resolution of multiphoton
      microscopy and the high detection efficiency and nanometer spectral resolution of
      a spectrograph were utilized to record spectral images of the intrinsic emission
      of mouse skin tissues. Autofluorescence from both cellular and extracellular
      structures, second-harmonic signal from collagen, and a narrowband emission
      related to Raman scattering of collagen were detected. Visualization of the
      spectral images by wavelength-to-RGB color image conversion allowed us to
      identify and discriminate tissue structures such as epidermal keratinocytes,
      lipid-rich corneocytes, intercellular structures, hair follicles, collagen,
      elastin, and dermal cells. Our results also showed morphological and spectral
      differences between excised tissue section, thick excised tissue, and in vivo
      tissue samples of mouse skin. Results on collagen excitation at different
      wavelengths suggested that the origin of the narrowband emission was collagen
      Raman peaks. Moreover, the oscillating spectral dependency of the collagen second
      harmonic intensity was experimentally studied. Overall, spectral imaging provided
      a wealth of information not easily obtainable with present conventional
      multiphoton imaging systems.

PMID- 17449668
TI  - Complexity of lipid domains and rafts in giant unilamellar vesicles revealed by
      combining imaging and microscopic and macroscopic time-resolved fluorescence.
AB  - The application of fluorescence lifetime imaging microscopy to study gel/fluid
      and raftlike lipid domains in giant unilamellar vesicles (GUVs) is demonstrated
      here. Different regions of the ternary
      dipalmitoylphosphatidylcholine/dioleoylphosphatidylcholine/cholesterol phase
      diagram were studied. The head-labeled phospholipid Rhodamine
      dioleoylphosphatidylethanolamine (Rhod-DOPE) was used as a fluorescent probe.
      Gel/fluid and liquid-ordered (l(o))/liquid-disordered (l(d)) phase separation
      were clearly visualized upon two-photon excitation. Fluorescence intensity decays
      in different regions of a GUV were also obtained with the microscope in fixed
      laser-beam configuration. The ensemble behavior of the system was studied by
      obtaining fluorescence intensity decays of Rhod-DOPE in nongiant vesicle
      suspensions. The fingerprints for gel/fluid coexistence and for the presence of
      l(o) raftlike phase, based on fluorescence lifetime imaging microscopy histograms
      and images, and on the fluorescence intensity decay parameters of Rhod-DOPE, are
      presented. The presence of three lipid phases in one single GUV is detected
      unequivocally. From the comparison of lifetime parameters, it can be concluded
      that the l(o) phase is formed in the binary
      dipalmitoylphosphatidylcholine/cholesterol but not in the
      dioleoylphosphatidylcholine/cholesterol mixture. The domains apparent in
      fluorescence intensity images have a more complex substructure revealed by
      analysis of the lifetime data. The potential applications of this combined
      imaging/microscopic/macroscopic methodology are discussed.

PMID- 17449669
TI  - Mechanics of force propagation in TonB-dependent outer membrane transport.
AB  - For the uptake of scarce yet essential organometallic compounds, outer membrane
      transporters of Gram-negative bacteria work in concert with an energy-generating
      inner membrane complex, thus spanning the periplasmic space to drive active
      transport. Here, we examine the interaction of TonB, an inner membrane protein,
      with an outer membrane transporter based upon a recent crystal structure of a
      TonB-transporter complex to characterize two largely unknown steps of the
      transport cycle: how energy is transmitted from TonB to the transporter and how
      energy transduction initiates transport. Simulations of TonB in complex with BtuB
      reveal that force applied to TonB is transmitted to BtuB without disruption of
      the very small connection between the two, supporting a mechanical mode of
      coupling. Based on the results of different pulling simulations, we propose that
      the force transduction instigates a partial unfolding of the pore-occluding
      luminal domain of the transporter, a potential step in the transport cycle.
      Furthermore, analysis of the electrostatic potentials and salt bridge
      interactions between the two proteins during the simulations hints at involvement
      of electrostatic forces in long-range interaction and binding of TonB and BtuB.

PMID- 17449670
TI  - NMR studies in dodecylphosphocholine of a fragment containing the seventh
      transmembrane helix of a G-protein-coupled receptor from Saccharomyces
      cerevisiae.
AB  - The structure and dynamics of a large segment of Ste2p, the G-protein-coupled
      alpha-factor receptor from yeast, were studied in dodecylphosphocholine (DPC)
      micelles using solution NMR spectroscopy. We investigated the 73-residue peptide
      EL3-TM7-CT40 consisting of the third extracellular loop 3 (EL3), the seventh
      transmembrane helix (TM7), and 40 residues from the cytosolic C-terminal domain
      (CT40). The structure reveals the presence of an alpha-helix in the segment
      encompassing residues 10-30, which is perturbed around the internal Pro-24
      residue. Root mean-square deviation values of individually superimposed helical
      segments 10-20 and 25-30 were 0.91 +/- 0.33 A and 0.76 +/- 0.37 A, respectively.
      15N-relaxation and residual dipolar coupling data support a rather stable fold
      for the TM7 part of EL3-TM7-CT40, whereas the EL3 and CT40 segments are more
      flexible. Spin-label data indicate that the TM7 helix integrates into DPC
      micelles but is flexible around the internal Pro-24 site, exposing residues 22-26
      to solution and reveal a second site of interaction with the micelle within a
      region comprising residues 43-58, which forms part of a less well-defined nascent
      helix. These findings are discussed in light of previous studies in organic
      aqueous solvent systems.

PMID- 17449671
TI  - Two-step mechanism of homogeneous nucleation of sickle cell hemoglobin polymers.
AB  - Sickle cell anemia is a debilitating genetic disease that affects hundreds of
      thousands of babies born each year worldwide. Its primary pathogenic event is the
      polymerization of a mutant, sickle cell, hemoglobin (HbS); and this is one of a
      line of diseases (Alzheimer's, Huntington's, prion, etc.) in which nucleation
      initiates pathophysiology. We show that the homogeneous nucleation of HbS
      polymers follows a two-step mechanism with metastable dense liquid clusters
      serving as precursor to the ordered nuclei of the HbS polymer. The evidence comes
      from data on the rates of fiber nucleation and growth and nucleation delay times,
      the interaction of fibers with polarized light, and mesoscopic metastable HbS
      clusters in solution. The presence of a precursor in the HbS nucleation mechanism
      potentially allows low-concentration solution components to strongly affect the
      nucleation kinetics. The variations of these concentrations in patients might
      account for the high variability of the disease in genetically identical
      patients. In addition, these components can potentially be utilized for control
      of HbS polymerization and treatment of the disease.

PMID- 17449672
TI  - Conformation of the EPEC Tir protein in solution: investigating the impact of
      serine phosphorylation at positions 434/463.
AB  - The translocated intimin receptor (Tir) is a key virulence factor of
      enteropathogenic Escherichia coli and related bacteria. During infection, Tir is
      translocated via a type III secretion system into host intestinal epithelial
      cells, where it inserts into the target cell membrane and acts as a receptor for
      the bacterial adhesin intimin. The effects of phosphorylation by cAMP-dependent
      kinase at two serine residues (Ser-434 and Ser-463) within the C-terminal domain
      of Tir, which may be involved in mediating structural/electrostatic changes in
      the protein to promote membrane insertion or intermolecular interactions, have
      previously been investigated. This study has focused on defining the conformation
      of Tir in solution and assessing any conformational changes associated with
      serine phosphorylation at positions 434/463. In addition to phosphorylated
      protein, combinations of Ala (unphosphorylatable) and Asp (phosphate-mimic)
      mutations of Ser-434 and Ser-463 have been generated, and a range of techniques
      (sodium dodecyl sulfate polyacrylamide gel electrophoresis, circular dichroism
      spectroscopy, analytical ultracentrifugation) used to further dissect the
      structural role and functional implications of changes in residue size/charge at
      these positions. The results have shown that under physiological NaCl
      concentrations, Tir is a monomer and adopts a highly elongated state in solution,
      consistent with a natively unfolded conformation. Despite this, perturbations in
      the structure in response to buffer conditions and the nature of the residues at
      positions 434 and 463 are apparent, and may be functionally relevant.

PMID- 17449674
TI  - The interaction of guanidinium ions with a model peptide.
AB  - In addition to promoting unfolded protein states, the denaturants urea and
      guanidinium (Gdm(+)) accumulate at the surface of folded proteins at
      subdenaturing concentrations, a phenomenon that correlates with their denaturant
      activities. The enhanced accumulation of Gdm(+) relative to urea indicates
      different binding modes, or additional binding sites, for Gdm(+), and we recently
      proposed potential binding modes to protein functional groups for Gdm(+) based on
      the determination of the weak hydration properties of this complex cation. Here
      we describe molecular dynamics simulations of a model helical peptide, melittin,
      in a 3 M solution of GdmCl, to identify potential interactions with amino-acid
      side chains in a nondenatured polypeptide surface. The simulations indicate that
      Gdm(+) can interact with a number of planar amino-acid side chains (Arg, Trp,
      Gln) in a stacking manner, as well as more weakly with hydrophobic surfaces
      composed of aliphatic side chains, and that these interactions result in enhanced
      number densities of Gdm(+) at certain locations on the peptide surface. These
      observations provide molecular scale insight into the accumulation of Gdm(+) at
      protein surfaces that has previously been observed experimentally.

PMID- 17449673
TI  - On the propensity of phosphatidylglycerols to form interdigitated phases.
AB  - We have determined the phase behavior of disaturated phosphatidylglycerols (PGs)
      of chain lengths n(CH2) = 14-18 at high pH and ionic strength using calorimetry,
      dilatometry, as well as x-ray diffraction. PGs with n(CH2) = 14 and 16 show
      thermotropic behavior similar to that of phosphatidylcholines (PCs). The
      area/lipid obtained in the gel phase is smaller than that reported for PCs
      despite the expected larger effective headgroup size. This can be explained by
      the tilting of the PG headgroup out of the bilayer plane, and we provide
      experimental evidence for a headgroup tilt transition. For distearoyl PG, we
      further find that the "usual" gel phase coexists with an interdigitated phase,
      which exhibits a transition from an orthorhombic into a hexagonal chain packing.
      The total amount of the interdigitated phase depends significantly on the
      temperature but is found to be largely independent of temperature equilibration
      time and different sample preparation protocols. Thus, the development of the
      interdigitated phase appears to be kinetically trapped. The formation of
      interdigitated phases in PGs at much smaller chain lengths than in PCs is of high
      relevance to interaction studies with antimicrobial peptides, as it provides a
      mechanism for the discrimination of membranes composed of different lipid
      species.

PMID- 17449675
TI  - Photoisomerization mechanism of rhodopsin and 9-cis-rhodopsin revealed by x-ray
      crystallography.
AB  - The primary photochemical process of the visual function has been investigated
      using the three crystallographic models, 11-cis-rhodopsin, all-trans
      bathorhodopsin, and the artificial isomeric 9-cis-rhodopsin. Detailed examination
      of the atomic displacements and dihedral angle changes of the retinal chromophore
      involved in the interconversion among these isomers suggests the mechanism of
      isomerization efficiency.

PMID- 17449676
TI  - Topological difference of core regulatory networks induces different entrainment
      characteristics of plant and animal circadian clocks.
AB  - The plant circadian rhythm is quickly entrained to the change of a light stimulus
      but the mammalian circadian rhythm shows a relatively slow entrainment. Where
      does such a different entrainment feature of plants and mammals originate? To
      answer this question, we have investigated circadian regulatory networks of
      various species and identified the respective core structures of plants and
      animals. The core circadian regulatory network of plants is composed of two
      coupled negative feedback loops while the core network of animals consists of
      coupled negative and positive feedback loops. In addition, the way of regulation
      (gene transcription or protein degradation) induced by a light stimulus differs
      depending on species. Mathematical simulations revealed that the topological
      difference of the core regulatory networks as well as the different way of
      regulation induced by a light stimulus leads to the different entrainment
      characteristics of plant and animal circadian clocks.

PMID- 17449677
TI  - iRED analysis of TAR RNA reveals motional coupling, long-range correlations, and
      a dynamical hinge.
AB  - The HIV-1 transactivation response RNA element (TAR), which is essential to the
      lifecycle of the virus, has been suggested, based on NMR and hydrodynamic
      measurements, to undergo substantial, collective, structural dynamics that are
      important for its function. To deal with the significant coupling between overall
      diffusional rotation and internal motion expected to exist in TAR, here we
      utilize an isotropic reorientational eigenmode dynamics analysis of simulated
      molecular trajectories to obtain a detailed description of TAR dynamics and an
      accurately quantified pattern of dynamical correlations. The analysis
      demonstrates the inseparability of internal and overall motional modes, confirms
      the existence and reveals the nature of collective domain dynamics, and
      additionally reveals that the hinge for these motions is centered on residues
      U23, C24, and C41. Results also indicate the existence of long-range
      communication between the loop and the core of the RNA, and between the loop and
      the bulge. Additionally, the isotropic reorientational eigenmode dynamics
      analysis explains, from a dynamical perspective, several existing biochemical
      mutational studies and suggests new mutations for future structural dynamics
      studies.

PMID- 17449679
TI  - Lactobacillus rhamnosus strain GG reduces aflatoxin B1 transport, metabolism, and
      toxicity in Caco-2 Cells.
AB  - The probiotic Lactobacillus rhamnosus GG is able to bind the potent
      hepatocarcinogen aflatoxin B1 (AFB1) and thus potentially restrict its rapid
      absorption from the intestine. In this study we investigated the potential of GG
      to reduce AFB1 availability in vitro in Caco-2 cells adapted to express
      cytochrome P-450 (CYP) 3A4, such that both transport and toxicity could be
      assessed. Caco-2 cells were grown as confluent monolayers on transmembrane
      filters for 21 days prior to all studies. AFB1 levels in culture medium were
      measured by high-performance liquid chromatography. In CYP 3A4-induced
      monolayers, AFB1 transport from the apical to the basolateral chamber was reduced
      from 11.1%+/-1.9% to 6.4%+/-2.5% (P=0.019) and to 3.3%+/-1.8% (P=0.002) within
      the first hour in monolayers coincubated with GG (1x10(10) and 5x10(10) CFU/ml,
      respectively). GG (1x10(10) and 5x10(10) CFU/ml) bound 40.1%+/-8.3% and 61.0%+/
      6.0% of added AFB1 after 1 h, respectively. AFB1 caused significant reductions of
      30.1% (P=0.01), 49.4% (P=0.004), and 64.4% (P<0.001) in transepithelial
      resistance after 24, 48, and 72 h, respectively. Coincubation with 1x10(10)
      CFU/ml GG after 24 h protected against AFB1-induced reductions in transepithelial
      resistance at both 24 h (P=0.002) and 48 h (P=0.04). DNA fragmentation was
      apparent in cells treated only with AFB1 cells but not in cells coincubated with
      either 1x10(10) or 5x10(10) CFU/ml GG. GG reduced AFB1 uptake and protected
      against both membrane and DNA damage in the Caco-2 model. These data are
      suggestive of a beneficial role of GG against dietary exposure to aflatoxin.

PMID- 17449678
TI  - A comprehensive calorimetric investigation of an entropically driven T cell
      receptor-peptide/major histocompatibility complex interaction.
AB  - The alphabeta T cell receptor (TCR) is responsible for recognizing peptides bound
      and "presented" by major histocompatibility complex (MHC) molecules. We recently
      reported that at 25 degrees C the A6 TCR, which recognizes the Tax peptide
      presented by the class I MHC human leukocyte antigen-A*0201 (HLA-A2), binds with
      a weak DeltaH degrees , a favorable DeltaS degrees , and a moderately negative
      DeltaC(p). These observations were of interest given the unfavorable binding
      entropies and large heat capacity changes measured for many other TCR-ligand
      interactions, suggested to result from TCR conformational changes occurring upon
      binding. Here, we further investigated the A6-Tax/HLA-A2 interaction using
      titration calorimetry. We found that binding results in a pK(a) shift,
      complicating interpretation of measured binding thermodynamics. To better
      characterize the interaction, we measured binding as a function of pH,
      temperature, and buffer ionization enthalpy. A global analysis of the resulting
      data allowed determination of both the intrinsic binding thermodynamics separated
      from the influence of protonation as well as the thermodynamics associated with
      the pK(a) shift. Our results indicate that intrinsically, A6 binds Tax/HLA-A2
      with a very weak DeltaH degrees , an even more favorable DeltaS degrees than
      previously thought, and a relatively large negative DeltaC(p). Comparison of
      these energetics with the makeup of the protein-protein interface suggests that
      conformational adjustments are required for binding, but these are more likely to
      be structural shifts, rather than disorder-to-order transitions. The
      thermodynamics of the pK(a) shift suggest protonation may be linked to an
      additional process such as ion binding.

PMID- 17449680
TI  - Risk of handling as a route of exposure to infectious waterborne Cryptosporidium
      parvum oocysts via Atlantic blue crabs (Callinectes sapidus).
AB  - Commercial Atlantic blue crabs (Callinectes sapidus) were exposed to 2.0x10(4)
      infectious waterborne oocysts of Cryptosporidium parvum. The study demonstrated
      that blue crabs can transfer C. parvum oocysts to persons involved in handling or
      preparing crabs and that they may contaminate other surfaces or products during
      storage.

PMID- 17449681
TI  - Recurrent and sporadic Listeria monocytogenes contamination in alheiras
      represents considerable diversity, including virulence-attenuated isolates.
AB  - Microbiological characterization of alheiras, traditional smoked meat sausages
      produced in northern Portugal, had previously shown that more than 60% of the
      lots analyzed were contaminated with Listeria monocytogenes at levels higher than
      100 CFU/g. In order to better understand L. monocytogenes contamination patterns
      in alheiras, we characterized 128 L. monocytogenes isolates from alheiras using a
      variety of subtyping techniques (i.e., molecular serotyping; arsenic, cadmium,
      and tetracycline resistance typing; and pulsed-field gel electrophoresis [PFGE]).
      Subtyping of isolates from products collected on two separate dates provided
      evidence for the persistence of specific L. monocytogenes PFGE types in the
      production and distribution chains of alheiras from four different processors. A
      subset of 21 isolates was further characterized using ribotyping and Caco-2 cell
      invasion assays to evaluate the pathogenic potential of L. monocytogenes present
      in alheiras. Caco-2 invasion assays revealed seven isolates with invasion
      efficiencies that were less than 20% of that of the control strain 10403S. All
      seven isolates had premature stop codons in inlA that represented three distinct
      mutations, which had previously been observed in isolates from the United States
      or France. Our findings indicate the need for a comprehensive approach to control
      L. monocytogenes in alheiras, including strategies to reduce persistence. The
      presence of considerable diversity in invasion phenotypes among L. monocytogenes
      strains present in alheiras, including the presence of subtypes likely to be
      virulence attenuated, may provide an opportunity to initially focus control
      strategies on the subtypes most likely to cause human disease.

PMID- 17449682
TI  - Quantitative assessment of contamination of fresh food produce of various retail
      types by human-virulent microsporidian spores.
AB  - This study demonstrated that fresh food produce, such as berries, sprouts, and
      green-leafed vegetables, sold at the retail level can contain potentially viable
      microsporidian spores of human-virulent species, such as Enterocytozoon bieneusi,
      Encephalitozoon intestinalis, and Encephalitozoon cuniculi, at quantities
      representing a threat of food-borne infection.

PMID- 17449683
TI  - The early response to acid shock in Lactobacillus reuteri involves the ClpL
      chaperone and a putative cell wall-altering esterase.
AB  - To be able to function as a probiotic, bacteria have to survive the passage
      through the gastrointestinal tract. We have examined survival and gene expression
      of Lactobacillus reuteri ATCC 55730 after a sudden shift in environmental acidity
      to a pH close to the conditions in the human stomach. More than 80% of the L.
      reuteri cells survived at pH 2.7 for 1 h. A genomewide expression analysis
      experiment using microarrays displayed 72 differentially expressed genes at this
      pH. The early response to severe acid shock in L. reuteri differed from long-term
      acid adaptation to milder acid stress studied in other lactic acid bacteria. The
      genes induced included the following: clpL, genes putatively involved in
      alterations of the cell membrane and the cell wall; genes encoding
      transcriptional regulators; phage genes; and genes of unknown function. Two
      genes, clpL, encoding an ATPase with chaperone activity, and lr1516, encoding a
      putative esterase, were selected for mutation analyses. The mutants were
      significantly more sensitive to acid than the wild type was. Thus, these genes
      could contribute to the survival of L. reuteri in the gastrointestinal tract.

PMID- 17449685
TI  - Preliminary evidence that American bullfrogs (Rana catesbeiana) are suitable
      hosts for Escherichia coli O157:H7.
AB  - We orally inoculated Rana catesbeiana tadpoles (n=23) and metamorphs (n=24) to
      test their suitability as hosts for Escherichia coli O157:H7. Tadpoles were
      housed in flowthrough aquaria and did not become infected. Metamorphs were housed
      in stagnant aquaria, and 54% tested positive through 14 days postinoculation,
      suggesting that they are suitable hosts for E. coli O157:H7.

PMID- 17449684
TI  - Diversity of environmental Mycobacterium isolates from hemodialysis water as
      shown by a multigene sequencing approach.
AB  - Here we used a multigene sequencing approach for the identification and molecular
      typing of environmental mycobacteria of the fast-growing subgroup. Strains were
      isolated from hemodialysis water and clinical samples. Eleven type strains of
      related species of the genus were also included in this study. To gain further
      insight into the diversity of the environmental mycobacteria, we analyzed several
      housekeeping genes (16S rRNA, ITS1, gyrB, hsp65, recA, rpoB, and sodA). No
      individual phylogenetic tree allowed good discrimination of all of the species
      studied. However, a concatenated and a consensus analysis, combining the genes,
      allowed better discrimination of each strain to the species level, and the
      increase in sequence size also led to greater tree robustness. This approach is
      useful not only for the discrimination and identification of environmental
      mycobacteria but also for their molecular typing and studies of population
      genetics. Our results demonstrate high genetic diversity among the isolates
      obtained, which are probably new species of the genus.

PMID- 17449686
TI  - Nitric oxide reductase-targeted real-time PCR quantification of denitrifier
      populations in soil.
AB  - The quantification of denitrifying bacteria is a component in the further
      understanding of denitrification processes in the environment. Real-time PCR
      primers were designed to target two segments of the denitrifier population
      (cnorB(P) [Pseudomonas mandelii and closely related strains] and cnorB(B) [Bosea,
      Bradyrhizobium, and Ensifer spp.]) in agricultural soils based on functional
      cnorB (nitric oxide reductase) gene sequences. Total population numbers were
      measured using 16S rRNA gene real-time PCR. Two soil microcosm experiments were
      conducted. Experiment 1 examined the response of the indigenous soil microbial
      population to the addition of 500 mg/kg glucose-C daily over 7 days in soil
      microcosms. Changes in the total population were correlated (r = 0.83) between
      16S rRNA gene copy numbers and microbial biomass carbon estimates. Members of the
      cnorB(P) population of denitrifiers showed typical r-strategy by being able to
      increase their proportion in the total population from starting levels of <0.1%
      to around 2.4% after a daily addition of 500 mg/kg glucose-C. The cnorB(B) guild
      was not able to increase its relative percentage of the total population in
      response to the addition of glucose-C, instead increasing copy numbers only in
      proportion with the total population measured by 16S rRNA genes. Experiment 2
      measured population dynamics in soil after the addition of various amounts of
      glucose-C (0 to 500 mg/kg) and incubation under denitrifying conditions. cnorB(P)
      populations increased proportionally with the amount of glucose-C added (from 0
      to 500 mg/kg). In soil microcosms, denitrification rates, respiration, and
      cnorB(P) population densities increased significantly with increasing rates of
      glucose addition. cnorB(B) guild densities did not increase significantly under
      denitrifying conditions in response to increasing C additions.

PMID- 17449687
TI  - Identification of a gene cluster enabling Lactobacillus casei BL23 to utilize myo
      inositol.
AB  - Genome analysis of Lactobacillus casei BL23 revealed that, compared to L. casei
      ATCC 334, it carries a 12.8-kb DNA insertion containing genes involved in the
      catabolism of the cyclic polyol myo-inositol (MI). Indeed, L. casei ATCC 334 does
      not ferment MI, whereas strain BL23 is able to utilize this carbon source. The
      inserted DNA consists of an iolR gene encoding a DeoR family transcriptional
      repressor and a divergently transcribed iolTABCDG1G2EJK operon, encoding a
      complete MI catabolic pathway, in which the iolK gene probably codes for a
      malonate semialdehyde decarboxylase. The presence of iolK suggests that L. casei
      has two alternative pathways for the metabolism of malonic semialdehyde: (i) the
      classical MI catabolic pathway in which IolA (malonate semialdehyde
      dehydrogenase) catalyzes the formation of acetyl-coenzyme A from malonic
      semialdehyde and (ii) the conversion of malonic semialdehyde to acetaldehyde
      catalyzed by the product of iolK. The function of the iol genes was verified by
      the disruption of iolA, iolT, and iolD, which provided MI-negative strains. By
      contrast, the disruption of iolK resulted in a strain with no obvious defect in
      MI utilization. Transcriptional analyses conducted with different mutant strains
      showed that the iolTABCDG1G2EJK cluster is regulated by substrate-specific
      induction mediated by the inactivation of the transcriptional repressor IolR and
      by carbon catabolite repression mediated by the catabolite control protein A
      (CcpA). This is the first example of an operon for MI utilization in lactic acid
      bacteria and illustrates the versatility of carbohydrate utilization in L. casei
      BL23.

PMID- 17449688
TI  - Structure and function of methanogens along a short-term restoration
      chronosequence in the Florida Everglades.
AB  - The removal of plants and soil to bedrock to eradicate exotic invasive plants
      within the Hole-in-the-Donut (HID) region, part of the Everglades National Park
      (Florida), presented a unique opportunity to study the redevelopment of soil and
      the associated microbial communities in the context of short-term primary
      succession and ecosystem restoration. The goal of this study was to identify
      relationships between soil redevelopment and activity and composition of
      methanogenic assemblages in HID soils. Methane production potentials indicated a
      general decline in methanogenic activity with restoration age. Microcosm
      incubations strongly suggested hydrogenotrophic methanogenesis as the most
      favorable pathway for methane formation in HID soils from all sites. Culture
      independent techniques targeting methyl coenzyme M reductase genes (mcrA) were
      used to assess the dynamics of methanogenic assemblages. Clone libraries were
      dominated by sequences related to hydrogenotrophic methanogens of the orders
      Methanobacteriales and Methanococcales and suggested a general decline in the
      relative abundance of Methanobacteriales mcrA with time since restoration.
      Terminal restriction fragment length polymorphism analysis indicated methanogenic
      assemblages remain relatively stable between wet and dry seasons. Interestingly,
      analysis of soils across the restoration chronosequence indicated a shift in
      Methanobacteriales populations with restoration age, suggesting genotypic shifts
      due to site-specific factors.

PMID- 17449689
TI  - Faster, simpler, more-specific methods for improved molecular detection of
      Phytophthora ramorum in the field.
AB  - Phytophthora ramorum is the causal agent of sudden oak death. The pathogen also
      affects a wide range of tree, shrub, and herbaceous species in natural and
      landscaped environments as well as plants in the nursery industry. A TaqMan real
      time PCR method for the detection of this pathogen in the field has been
      described previously; this paper describes the development of a number of assays
      based on this method which have various advantages for use in the field. A
      scorpion real-time PCR assay that is twice as fast as TaqMan was developed,
      allowing the detection of P. ramorum in less than 30 min. Also designed was a
      loop-mediated isothermal amplification (LAMP) assay, which allowed sensitive and
      specific detection of P. ramorum in 45 min using only a heated block. A positive
      reaction was identified by the detection of the LAMP product by color change
      visible to the naked eye.

PMID- 17449690
TI  - Coprinus comatus damages nematode cuticles mechanically with spiny balls and
      produces potent toxins to immobilize nematodes.
AB  - We reported recently a unique fungal structure, called the spiny ball, on the
      vegetative hyphae of Coprinus comatus (O. F. Mull.:Fr.) Pers. Although some
      observations regarding the role of this structure were presented, its function
      remained largely unknown. In this study, we showed that purified (isolated and
      washed) spiny balls could immobilize and kill the free-living nematode
      Panagrellus redivivus Goodey highly efficiently. Scanning electron microscopy
      studies illustrated that the spiny structure damaged the nematode cuticle,
      suggesting the presence of a mechanical force during the process of nematode
      immobilization. Severe injuries on nematode cuticles caused the leakage of inner
      materials of the nematodes. When these structures were ground in liquid nitrogen,
      their killing efficacy against nematodes was lost, indicating that the shape and
      the complete structure of the spiny balls are indispensable for their function.
      However, extraction with organic solvents never lowered their activity against P.
      redivivus, and the extracts showed no obvious effect on the nematode. We also
      investigated whether C. comatus was able to produce toxins which would aid in the
      immobilization of nematodes. In total, we identified seven toxins from C. comatus
      that showed activity to immobilize the nematodes P. redivivus and Meloidogyne
      incognita (Kofoid et White) Chitwood. The chemical structures of these toxins
      were identified with nuclear magnetic resonance, mass spectrometry, infrared, and
      UV spectrum analysis. Two compounds were found to be novel. The toxins found in
      C. comatus are O-containing heterocyclic compounds.

PMID- 17449691
TI  - Plant cell wall degradation by saprophytic Bacillus subtilis strains: gene
      clusters responsible for rhamnogalacturonan depolymerization.
AB  - Plant cell wall degradation is a premier event when Bacillus subtilis, a typical
      saprophytic bacterium, invades plants. Here we show the degradation system of
      rhamnogalacturonan type I (RG-I), a component of pectin from the plant cell wall,
      in B. subtilis strain 168. Strain 168 cells showed a significant growth on plant
      cell wall polysaccharides such as pectin, polygalacturonan, and RG-I as a carbon
      source. DNA microarray analysis indicated that three gene clusters
      (yesOPQRSTUVWXYZ, ytePQRST, and ybcMOPST-ybdABDE) are inducibly expressed in
      strain 168 cells grown on RG-I. Cells of an industrially important bacterium, B.
      subtilis strain natto, fermenting soybeans also express the gene cluster
      including the yes series during the assimilation of soybean used as a carbon
      source. Among proteins encoded in the yes cluster, YesW and YesX were found to be
      novel types of RG lyases releasing disaccharide from RG-I. Genetic and enzymatic
      properties of YesW and YesX suggest that strain 168 cells secrete YesW, which
      catalyzes the initial cleavage of the RG-I main chain, and the resultant
      oligosaccharides are converted to disaccharides through the extracellular exotype
      YesX reaction. The disaccharide is finally degraded into its constituent
      monosaccharides through the reaction of intracellular unsaturated galacturonyl
      hydrolases YesR and YteR. This enzymatic route for RG-I degradation in strain 168
      differs significantly from that in plant-pathogenic fungus Aspergillus aculeatus.
      This is, to our knowledge, the first report on the bacterial system for complete
      RG-I main chain degradation.

PMID- 17449692
TI  - DNA microarray-based identification of serogroups and virulence gene patterns of
      Escherichia coli isolates associated with porcine postweaning diarrhea and edema
      disease.
AB  - Escherichia coli strains causing postweaning diarrhea (PWD) and edema disease
      (ED) in pigs are limited to a number of serogroups, with O8, O45, O138, O139,
      O141, O147, O149, and O157 being the most commonly reported worldwide. In this
      study, a DNA microarray based on the O-antigen-specific genes of all 8 E. coli
      serogroups, as well as 11 genes encoding adhesion factors and exotoxins
      associated with PWD and ED, was developed for the identification of related
      serogroups and virulence gene patterns. The microarray method was tested against
      186 E. coli and Shigella O-serogroup reference strains, 13 E. coli reference
      strains for virulence markers, 43 E. coli clinical isolates, and 12 strains of
      other bacterial species and shown to be highly specific with reproducible
      results. The detection sensitivity was 0.1 ng of genomic DNA or 10(3) CFU per 0.3
      g of porcine feces in mock samples. Seventeen porcine feces samples from local
      hoggeries were examined using the microarray, and the result for one sample was
      verified by the conventional serotyping methods. This microarray can be readily
      used to screen for the presence of PWD- and ED-associated E. coli in porcine
      feces samples.

PMID- 17449693
TI  - Swarming behavior of and hemolysin BL secretion by Bacillus cereus.
AB  - An association between swarming and hemolysin BL secretion was observed in a
      collection of 42 Bacillus cereus isolates (P=0.029). The highest levels of toxin
      were detected in swarmers along with swarm cell differentiation (P=0.021),
      suggesting that swarming B. cereus strains may have a higher virulence potential
      than nonswarming strains.

PMID- 17449694
TI  - Desensitization of feedback inhibition of the Saccharomyces cerevisiae gamma
      glutamyl kinase enhances proline accumulation and freezing tolerance.
AB  - In response to osmotic stress, proline is accumulated in many bacterial and plant
      cells as an osmoprotectant. The yeast Saccharomyces cerevisiae induces trehalose
      or glycerol synthesis but does not increase intracellular proline levels during
      various stresses. Using a proline-accumulating mutant, we previously found that
      proline protects yeast cells from damage by freezing, oxidative, or ethanol
      stress. This mutant was recently shown to carry an allele of PRO1 which encodes
      the Asp154Asn mutant gamma-glutamyl kinase (GK), the first enzyme of the proline
      biosynthetic pathway. Here, enzymatic analysis of recombinant proteins revealed
      that the GK activity of S. cerevisiae is subject to feedback inhibition by
      proline. The Asp154Asn mutant was less sensitive to feedback inhibition than wild
      type GK, leading to proline accumulation. To improve the enzymatic properties of
      GK, PCR random mutagenesis in PRO1 was employed. The mutagenized plasmid library
      was introduced into an S. cerevisiae non-proline-utilizing strain, and proline
      overproducing mutants were selected on minimal medium containing the toxic
      proline analogue azetidine-2-carboxylic acid. We successfully isolated several
      mutant GKs that, due to extreme desensitization to inhibition, enhanced the
      ability to synthesize proline better than the Asp154Asn mutant. The amino acid
      changes were localized at the region between positions 142 and 154, probably on
      the molecular surface, suggesting that this region is involved in allosteric
      regulation. Furthermore, we found that yeast cells expressing Ile150Thr and
      Asn142Asp/Ile166Val mutant GKs were more tolerant to freezing stress than cells
      expressing the Asp154Asn mutant.

PMID- 17449695
TI  - Trehalose biosynthesis in Rhizobium leguminosarum bv. trifolii and its role in
      desiccation tolerance.
AB  - Rhizobium leguminosarum bv. trifolii forms nitrogen-fixing root nodules on the
      pasture legume Trifolium repens, and T. repens seed is often coated with a
      compatible R. leguminosarum bv. trifolii strain prior to sowing. However,
      significant losses in bacterial viability occur during the seed-coating process
      and during storage of the coated seeds, most likely due to desiccation stress.
      The disaccharide trehalose is known to function as an osmoprotectant, and
      trehalose accumulation due to de novo biosynthesis is a common response to
      desiccation stress in bacteria. In this study we investigated the role of
      endogenous trehalose synthesis in desiccation tolerance in R. leguminosarum bv.
      trifolii strain NZP561. Strain NZP561 accumulated trehalose as it entered the
      stationary phase due to the combined actions of the TreYZ and OtsAB pathways.
      Mutants deficient in either pathway showed near-wild-type levels of trehalose
      accumulation, but double otsA treY mutants failed to accumulate any trehalose.
      The double mutants were more sensitive to the effects of drying, and their
      survival was impaired compared to that of the wild type when glass beads were
      coated with the organisms and stored at relative humidities of 5 and 32%. The
      otsA treY mutants were also less competitive for nodule occupancy. Gene
      expression studies showed that the otsA and treY genes were expressed
      constitutively and that expression was not influenced by the growth phase,
      suggesting that trehalose accumulation is controlled at the posttranscriptional
      level or by control of trehalose breakdown rates. Our results indicate that
      accumulated trehalose plays an important role in protecting R. leguminosarum bv.
      trifolii cells against desiccation stress and against stress encountered during
      nodulation.

PMID- 17449696
TI  - Characterization of Staphylococcus aureus isolates from buffalo, bovine, ovine,
      and caprine milk samples collected in Rio de Janeiro State, Brazil.
AB  - Eighty-four staphylococcal isolates were obtained from milk samples from cows,
      sheep, goats, and buffalo with subclinical mastitis and from colonization samples
      from ostriches. The animals were hosted in 18 small dairy herds and an ostrich
      breeding located in 10 municipalities of the state of Rio de Janeiro, Brazil.
      Thirty isolates were identified as Staphylococcus aureus by biochemical and
      molecular techniques and were comparatively characterized by phenotypic and
      genotypic methods. The molecular characterization by pulsed-field gel
      electrophoresis (PFGE), spa typing, and multilocus sequence typing (MLST)
      revealed five clonal types (PFGE A, spa type t359, sequence type 747 [ST747];
      PFGE B, spa type t1180, ST750; PFGE C, spa type t605, ST126; PFGE D, spa type
      t127, ST751; and PFGE F, spa type t002, ST5). None of the isolates harbored the
      Panton-Valentine leukocidin or exfoliative toxin D gene. The detection of major
      clone A (in 63% of the isolates) in different herds, among all animal species
      studied, and in infection and colonization samples evidenced its geographical
      spread among Rio de Janeiro State and no host preference among the animal
      species. Comparison with S. aureus from a human origin suggested that all but one
      clone found in the present study might be animal specific.

PMID- 17449697
TI  - Diversity and function of Chloroflexus-like bacteria in a hypersaline microbial
      mat: phylogenetic characterization and impact on aerobic respiration.
AB  - We studied the diversity of Chloroflexus-like bacteria (CLB) in a hypersaline
      phototrophic microbial mat and assayed their near-infrared (NIR) light-dependent
      oxygen respiration rates. PCR with primers that were reported to specifically
      target the 16S rRNA gene from members of the phylum Chloroflexi resulted in the
      recovery of 49 sequences and 16 phylotypes (sequences of the same phylotype share
      more than 96% similarity), and 10 of the sequences (four phylotypes) appeared to
      be related to filamentous anoxygenic phototrophic members of the family
      Chloroflexaceae. Photopigment analysis revealed the presence of
      bacteriochlorophyll c (BChlc), BChld, and gamma-carotene, pigments known to be
      produced by phototrophic CLB. Oxygen microsensor measurements for intact mats
      revealed a NIR (710 to 770 nm) light-dependent decrease in aerobic respiration, a
      phenomenon that we also observed in an axenic culture of Chloroflexus
      aurantiacus. The metabolic ability of phototrophic CLB to switch from anoxygenic
      photosynthesis under NIR illumination to aerobic respiration under non-NIR
      illumination was further used to estimate the contribution of these organisms to
      mat community respiration. Steady-state oxygen profiles under dark conditions and
      in the presence of visible (VIS) light (400 to 700 nm), NIR light (710 to 770
      nm), and VIS light plus NIR light were compared. NIR light illumination led to a
      substantial increase in the oxygen concentration in the mat. The observed impact
      on oxygen dynamics shows that CLB play a significant role in the cycling of
      carbon in this hypersaline microbial mat ecosystem. This study further
      demonstrates that the method applied, a combination of microsensor techniques and
      VIS and NIR illumination, allows rapid establishment of the presence and
      significance of CLB in environmental samples.

PMID- 17449698
TI  - Kinetic constant variability in bacterial oxidation of elemental sulfur.
AB  - Wide ranges of growth yields on sulfur (from 2.4 x 10(10) to 8.1 x 10(11) cells
      g(-1)) and maximum sulfur oxidation rates (from 0.068 to 1.30 mmol liter(-1) h(
      1)) of an Acidithiobacillus ferrooxidans strain (CCM 4253) were observed in 73
      batch cultures. No significant correlation between the constants was observed.
      Changes of the Michaelis constant for sulfur (from 0.46 to 15.5 mM) in resting
      cells were also noted.

PMID- 17449699
TI  - Detection and transformation of genome segments that differ within a coastal
      population of Vibrio cholerae strains.
AB  - Vibrio cholerae is an autochthonous member of diverse aquatic ecosystems around
      the globe. Collectively, the genomes of environmental V. cholerae strains
      comprise a large repository of encoded functions which can be acquired by
      individual V. cholerae lineages through uptake and recombination. To characterize
      the genomic diversity of environmental V. cholerae, we used comparative genome
      hybridization to study 41 environmental strains isolated from diverse habitats
      along the central California coast, a region free of endemic cholera. These data
      were used to classify genes of the epidemic V. cholerae O1 sequenced strain
      N16961 as conserved, variably present, or absent from the isolates. For the most
      part, absent genes were restricted to large mobile elements and have known
      functions in pathogenesis. Conversely, genes present in some, but not all,
      California isolates were in smaller contiguous clusters and were less likely to
      be near genes with functions in DNA mobility. Two such clusters of variable genes
      encoding different selectable metabolic phenotypes (mannose and diglucosamine
      utilization) were transformed into the genomes of environmental isolates by
      chitin-dependent competence, indicating that this mechanism of general genetic
      exchange is conserved among V. cholerae. The transformed DNA had an average size
      of 22.7 kbp, demonstrating that natural competence can mediate the movement of
      large chromosome fragments. Thus, whether variable genes arise through the
      acquisition of new sequences by horizontal gene transfer or by the loss of
      preexisting DNA though deletion, natural transformation provides a mechanism by
      which V. cholerae clones can gain access to the V. cholerae pan-genome.

PMID- 17449700
TI  - Shedding of Escherichia coli O157:H7 in calves is reduced by prior colonization
      with the homologous strain.
AB  - Enterohemorrhagic Escherichia coli O157:H7 has a natural reservoir in the
      intestinal tracts of cattle. Colonization is asymptomatic and transient, but it
      is not clear if protective immunity is induced. This study demonstrates that
      prior colonization induces humoral immune responses to bacterial antigens and
      reduces bacterial shedding after experimental challenge with the homologous
      strain.

PMID- 17449701
TI  - Sonoporation is an efficient tool for intracellular fluorescent dextran delivery
      and one-step double-crossover mutant construction in Fusobacterium nucleatum.
AB  - Studies of microorganisms are often hindered by a lack of effective genetic
      tools. One such example is Fusobacterium nucleatum, a gram-negative anaerobe
      associated with various human infections, including those causing periodontal
      disease and preterm birth. The first double-crossover allelic-exchange mutant in
      F. nucleatum was recently constructed using sonoporation, a novel ultrasound
      mediated intracellular delivery method, demonstrating potential for bacterial
      gene transfection. To better unveil its mechanism, the current study examines the
      factors affecting the outcome of sonoporation. Delivery of Texas Red-conjugated
      dextran into F. nucleatum by sonoporation was at least twice as efficient as that
      by electroporation, and sonoporation was nonbactericidal, unlike electroporation.
      The delivery efficiency was affected by the acoustic pressure amplitude, the duty
      cycle, and the quantity of microbubbles used to initiate cavitation but not by
      the pulse repetition frequency of ultrasound application. To examine the
      involvement of homologous recombination in sonoporation-mediated mutant
      construction, the highly conserved recA gene, which carried most of the consensus
      residues, including the P loop, was identified in F. nucleatum, and a double
      crossover recA mutant of F. nucleatum 12230, US1610, was constructed by
      sonoporation. The mutant exhibited increased sensitivity to UV exposure compared
      with that of the wild type, indicating that the RecA function in F. nucleatum was
      conserved. Interestingly, US1610 was also sensitive to ultrasound treatment,
      suggesting the likely involvement of RecA in postsonoporation repair and
      survival. Since sonoporation has consistently generated one-step double-crossover
      mutants in F. nucleatum by use of intact suicide plasmids, this technology may be
      developed into an efficient tool for streamlining mutant construction in
      bacteria.

PMID- 17449702
TI  - Genomic and phenotypic diversity of coastal Vibrio cholerae strains is linked to
      environmental factors.
AB  - Studies of Vibrio cholerae diversity have focused primarily on pathogenic
      isolates of the O1 and O139 serotypes. However, autochthonous environmental
      isolates of this species routinely display more extensive genetic diversity than
      the primarily clonal pathogenic strains. In this study, genomic and metabolic
      profiles of 41 non-O1/O139 environmental isolates from central California coastal
      waters and four clinical strains are used to characterize the core genome and
      metabolome of V. cholerae. Comparative genome hybridization using microarrays
      constructed from the fully sequenced V. cholerae O1 El Tor N16961 genome
      identified 2,787 core genes that approximated the projected species core genome
      within 1.6%. Core genes are almost universally present in strains with widely
      different niches, suggesting that these genes are essential for persistence in
      diverse aquatic environments. In contrast, the dispensable genes and phenotypic
      traits identified in this study should provide increased fitness for certain
      niche environments. Environmental parameters, measured in situ during sample
      collection, are correlated to the presence of specific dispensable genes and
      metabolic capabilities, including utilization of mannose, sialic acid, citrate,
      and chitosan oligosaccharides. These results identify gene content and metabolic
      pathways that are likely selected for in certain coastal environments and may
      influence V. cholerae population structure in aquatic environments.

PMID- 17449703
TI  - Characterization of SafC, a catechol 4-O-methyltransferase involved in saframycin
      biosynthesis.
AB  - Members of the saframycin/safracin/ecteinascidin family of peptide natural
      products are potent antitumor agents currently under clinical development.
      Saframycin MX1, from Myxococcus xanthus, is synthesized by a nonribosomal peptide
      synthetase, SafAB, and an O-methyltransferase, SafC, although other proteins are
      likely involved in the pathway. SafC was overexpressed in Escherichia coli,
      purified to homogeneity, and assayed for its ability to methylate a variety of
      substrates. SafC was able to catalyze the O-methylation of catechol derivatives
      but not phenols. Among the substrates tested, the best substrate for SafC was L
      dihydroxyphenylalanine (L-dopa), which was methylated specifically in the 4'-O
      position (k(cat)/K(m) = 5.5 x 10(3) M(-1) s(-1)). SafC displayed less activity on
      other catechol derivatives, including catechol, dopamine, and caffeic acid. The
      more labile l-5'-methyldopa was an extremely poor substrate for SafC (k(cat)/K(m)
      = approximately 2.8 x 10(-5) M(-1) s(-1)). L-dopa thioester derivatives were also
      much less reactive than L-dopa. These results indicate that SafC-catalyzed 4'-O
      methylation of L-dopa occurs prior to 5'-C-methylation, suggesting that 4'-O
      methylation is likely the first committed step in the biosynthesis of saframycin
      MX1. SafC has biotechnological potential as a methyltransferase with unique
      regioselectivity.

PMID- 17449704
TI  - Diversity and mechanisms of alkali tolerance in lactobacilli.
AB  - We determined the maximum pH that allows growth (pHmax) for 34 strains of
      lactobacilli. High alkali tolerance was exhibited by strains of Lactobacillus
      casei, L. paracasei subsp. tolerans, L. paracasei subsp. paracasei, L. curvatus,
      L. pentosus, and L. plantarum that originated from plant material, with pHmax
      values between 8.5 and 8.9. Among these, L. casei NRIC 1917 and L. paracasei
      subsp. tolerans NRIC 1940 showed the highest pHmax, at 8.9. Digestive tract
      isolates of L. gasseri, L. johnsonii, L. reuteri, L. salivarius subsp.
      salicinius, and L. salivarius subsp. salivarius exhibited moderate alkali
      tolerance, with pHmax values between 8.1 and 8.5. Dairy isolates of L.
      delbrueckii subsp. bulgaricus, L. delbrueckii subsp. lactis, and L. helveticus
      exhibited no alkali tolerance, with pHmax values between 6.7 and 7.1. Measurement
      of the internal pH of representative strains revealed the formation of
      transmembrane proton gradients (DeltapH) in a reversed direction (i.e., acidic
      interior) at alkaline external-pH ranges, regardless of their degrees of alkali
      tolerance. Thus, the reversed DeltapH did not determine alkali tolerance
      diversity. However, the DeltapH contributed to alkali tolerance, as the pHmax
      values of several strains decreased with the addition of nigericin, which
      dissipates DeltapH. Although neutral external-pH values resulted in the highest
      glycolysis activity in the presence of nigericin regardless of alkali tolerance,
      substantial glucose utilization was still detected in the alkali-tolerant
      strains, even in a pH range of between 8.0 and 8.5, at which the remaining
      strains lost most activity. Therefore, the alkali tolerance of glycolysis
      reactions contributes greatly to the determination of alkali tolerance diversity.

PMID- 17449705
TI  - Quantitative detection of Clostridium tyrobutyricum in milk by real-time PCR.
AB  - We developed a real-time PCR assay for the quantitative detection of Clostridium
      tyrobutyricum, which has been identified as the major causal agent of late
      blowing in cheese. The assay was 100% specific, with an analytical sensitivity of
      1 genome equivalent in 40% of the reactions. The quantification was linear (R(2)
      > 0.9995) over a 5-log dynamic range, down to 10 genome equivalents, with a PCR
      efficiency of >0.946. With optimized detergent treatment and enzymatic
      pretreatment of the sample before centrifugation and nucleic acid extraction, the
      assay counted down to 300 C. tyrobutyricum spores, with a relative accuracy of
      82.98 to 107.68, and detected as few as 25 spores in 25 ml of artificially
      contaminated raw or ultrahigh-temperature-treated whole milk.

PMID- 17449707
TI  - A tragically naive Canadian law for tragically neglected global health.

PMID- 17449706
TI  - Protein engineering of wzc to generate new emulsan analogs.
AB  - Acinetobacter venetianus Rag1 produces an extracellular, polymeric
      lipoheteropolysaccharide termed apoemulsan. This polymer is putatively produced
      via a Wzy-dependent pathway. According to this model, the length of the polymer
      is regulated by polysaccharide-copolymerase (PCP) protein. A highly conserved
      proline and glycine motif was identified in all members of the PCP family of
      proteins and is involved in regulation of polymer chain length. In order to
      control the structure of apoemulsan, defined point mutations in the proline
      glycine-rich region of the apoemulsan PCP protein (Wzc) were introduced. Modified
      wzc variants were introduced into the Rag1 genome via homologous recombination.
      Stable chromosomal mutants were confirmed by Southern blot analysis. The
      molecular weight of the polymer was analyzed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. Five of the eight point mutants produced
      polymers having molecular weights higher than the molecular weight of the polymer
      produced by the wild type. Moreover, four of these five polymers had modified
      biological properties. Replacement of arginine by leucine (R418L) resulted in the
      most significant change in the molecular weight of the polymer. The R418L mutant
      was the most hydrophilic mutant, exhibiting decreased adherence to polystyrene,
      and inhibited biofilm formation. The results described in this report show the
      functional effect of Wzc modification on the molecular weight of a high-molecular
      weight polysaccharide. Moreover, in the present study we developed a genetic
      system to control polymerization of apoemulsan. The use of selective exogenous
      fatty acid feeding strategies, as well as genetic manipulation of sugar backbone
      chain length, is a promising new approach for bioengineering emulsan analogs.

PMID- 17449708
TI  - Attitudes of veterinary nurses to the assessment of pain and the use of pain
      scales.
AB  - In April 2004, a questionnaire was distributed to veterinary nurses across the UK
      to assess their attitudes towards the assessment and management of pain in
      practice. During the six-week collection period, a total of 541 questionnaires
      were returned, of which 24 (4.25 per cent) were discounted due to completion
      errors. Overall, the pain scores for procedures involving dogs were higher than
      those for cats; the veterinary nurses' pain scores were higher for all procedures
      than those of veterinary surgeons in a previous study. Both veterinary nurses and
      veterinary surgeons were primarily involved with monitoring pain postoperatively,
      and 96 per cent of veterinary nurses felt that their knowledge of pain management
      could be enhanced; 8.1 per cent of the practices used a formal pain scoring
      system, with the simple descriptive scale most commonly used; 80.3 per cent of
      the veterinary nurses agreed that a pain scale was a useful clinical tool.

PMID- 17449709
TI  - Effect of passive stretching on the range of motion of osteoarthritic joints in
      10 labrador retrievers.
AB  - Ten labrador retrievers and their owners undertook a programme to determine the
      effect of passive stretching on the dogs' osteoarthritic joints, which had a
      restricted range of motion. The range of motion of the joints was measured before
      and after the 21-day study, during which the owners performed 10 passive
      stretches for a hold of 10 seconds twice daily. Goniometric measurements showed
      that the passive stretching had significantly increased the range of motion of
      the joints.

PMID- 17449710
TI  - Responses of horses offered a choice between stables containing single or
      multiple forages.
AB  - To investigate the choices of foraging location of horses, 10 to 12 horses were
      introduced for five minutes into each of two similar stables containing a single
      forage or six forages, in four replicated trials. The horses were then removed
      and released into the gangway between the stables, and allowed five minutes to
      choose between the stables. Their initial and final choices, mean duration in
      each stable and proportional frequency of change of location were compared. Most
      of the horses initially entered the closest stable on release (P<0.05); if the
      closest stable contained a single hay, most horses transferred to the stable
      containing multiple forages (P<0.001). The length of time spent by the horses in
      the two stables suggested that they preferred multiple forages in multiple
      locations (P<0.001). Eleven horses moved from one stable to the other on one or
      more occasions during trials when hay or a preferred forage was available in both
      stables, possibly indicating a motivation to move between foraging locations
      regardless of the palatability of the forages offered or the horses' preference
      for a forage.

PMID- 17449711
TI  - Equine rhinosporidiosis: an exotic disease in the UK.

PMID- 17449712
TI  - Outbreak of clinical infectious laryngotracheitis in Turkey.

PMID- 17449713
TI  - Toxocara vitulorum in American bison (Bison bison) calves.

PMID- 17449714
TI  - Recurrent and metastatic canine urethral transitional cell carcinoma without
      bladder involvement.

PMID- 17449715
TI  - Complaints and stress in practice.

PMID- 17449716
TI  - Canine inflammatory bowel disease.

PMID- 17449717
TI  - Withdrawal of routine brucellosis testing in beef herds.

PMID- 17449718
TI  - The activin A-follistatin system: potent regulator of human extracellular matrix
      mineralization.
AB  - Bone quality is an important determinant of osteoporosis, and proper osteoblast
      differentiation plays an important role in the control and maintenance of bone
      quality. We investigated the impact of activin signaling on human osteoblast
      differentiation, extracellular matrix formation, and mineralization. Activins
      belong to the transforming growth factor-beta superfamily and activin A treatment
      strongly inhibited mineralization in osteoblast cultures, whereas the activin
      antagonist follistatin increased mineralization. Osteoblasts produced activin A
      and follistatin in a differentiation-dependent manner, leading to autocrine
      regulation of extracellular matrix formation and mineralization. In addition,
      mineralization in a vascular smooth muscle cell-based model for pathological
      calcification was inhibited. Comparative activin A and follistatin gene
      expression profiling showed that activin signaling changes the expression of a
      specific range of extracellular matrix proteins prior to the onset of
      mineralization, leading to a matrix composition with reduced or no mineralizing
      capacity. These findings demonstrate the regulation of osteoblast differentiation
      and matrix mineralization by the activin A-follistatin system, providing the
      possibility to control bone quality as well as pathological calcifications such
      as atherosclerosis by using activin A, follistatin, or analogs thereof.

PMID- 17449719
TI  - Sphingosine-1-phosphate and the immunosuppressant, FTY720-phosphate, regulate
      detrusor muscle tone.
AB  - Overactive bladder syndrome (OBS) results from disturbances of bladder function.
      Bladder smooth muscle (detrusor) exhibits spontaneous rhythmic activity (tone)
      independent of neurogenic control, which is enhanced in patients with OBS. We
      have now uncovered a prominent role for the bioactive sphingolipid metabolite,
      sphingosine-1-phosphate (S1P), in regulating rabbit detrusor smooth muscle tone
      and contraction. S1P-induced contraction of detrusor muscle was dependent on
      stretch and intracellular calcium. Although detrusor expresses the S1P receptors
      S1P1 and S1P2, only S1P2 appeared to be involved in S1P-induced contraction,
      since SEW2871 (S1P1 agonist) and dihydro-S1P (potent agonist for all S1P
      receptors except S1P2) were poor contractile agents. In agreement, the S1P2
      antagonist JTE013 inhibited S1P-induced contraction. The fast, transient muscle
      contraction (phasic) mediated by S1P was dependent on phospholipase C (PLC)
      whereas the slower, sustained contraction (tonic) was not. Surprisingly, the
      immunosuppressant FTY720-phosphate, an agonist for all S1P receptors except S1P2,
      had distinct contractile properties and also induced slow, sustained contraction.
      Thus, FTY720-phosphate and/or S1P may regulate calcium channels in an S1P
      receptor-independent manner. Collectively, our results demonstrate that S1P may
      regulate detrusor smooth muscle tone and suggest that dysregulation of complex
      S1P signaling might contribute to OBS.

PMID- 17449720
TI  - Biochemical consequences of the NOS3 Glu298Asp variation in human endothelium:
      altered caveolar localization and impaired response to shear.
AB  - Human endothelial nitric oxide synthase (NOS3) gene polymorphism at Exon 7
      (Glu298Asp) has been linked to vascular endothelial dysfunction, but the
      mechanisms are not defined. Shear is a key modulator of NOS3 function in vivo and
      association with caveolae is important for the control of NOS3 protein activity.
      Here we tested the hypothesis that altered enrichment of NOS3 in the caveolar
      membrane defines Glu298Asp genotype-specific responses and NOS3 activity. Basal
      caveolar membrane enrichment was carried out to quantitate the NOS3 enrichment in
      caveolae. Cells were subjected to shear and NOS3 protein levels, phosphorylation,
      enzyme function were investigated. Variant genotypes had lower NOx production pre
      and post-shear, but no genotype-dependent alterations in pNOS3 were observed.
      Asp variants had significantly lower NOS3 enrichment in the caveolar membrane
      fraction. Further, immunoprecipitation studies demonstrated that Asp variants had
      substantially less NOS3/Cav-1 association (approximately 40%) during static
      conditions. Furthermore, acute shear causes impaired NOS3/Cav-1 dissociation in
      Asp variants. The results from immunoprecipitation studies were in complete
      agreement with caveolar membrane preparation findings. Collectively, these data
      demonstrate functional consequences of the Glu298Asp NOS3 variation and further
      define disruption of NOS3 caveolar localization and shear-induced mobilization as
      the primary mechanism responsible for these differences.

PMID- 17449721
TI  - Telomere 3' overhang-specific DNA oligonucleotides induce autophagy in malignant
      glioma cells.
AB  - Telomere 3' overhang-specific DNA oligonucleotides (T-oligos) induce cell death
      in cancer cells, presumably by mimicking telomere loop disruption. Therefore, T
      oligos are considered an exciting new therapeutic strategy. The purpose of this
      study was to elucidate how T-oligos exert antitumor effects on human malignant
      glioma cells in vitro and in vivo. We demonstrated that T-oligos inhibited the
      proliferation of malignant glioma cells through induction of nonapoptotic cell
      death and mitochondria hyperpolarization, whereas normal astrocytes were
      resistant to T-oligos. Tumor cells treated with T-oligos developed features
      compatible with autophagy, with development of autophagic vacuoles and conversion
      of an autophagy-related protein, microtubule-associated protein 1 light chain 3
      from type I (cytoplasmic form) to type II (membrane form of autophagic vacuoles).
      A reverse-phase protein microarray analysis and Western blotting revealed that
      treatment with T-oligos inhibited the mammalian target of the rapamycin (mTOR)
      and the signal transducer and activator of transcription 3 (STAT3). Moreover,
      pretreatment with T-oligos significantly prolonged the survival time of mice
      inoculated intracranially with malignant glioma cells compared with that of
      untreated mice and those treated with control oligonucleotides (P=0.0065 and
      P=0.043, respectively). These results indicate that T-oligos stimulate the
      induction of nonapoptotic autophagic also known as type II programmed cell death
      and are thus promising in the treatment of malignant glioma.

PMID- 17449722
TI  - Lung-specific nuclear reprogramming is accompanied by heterokaryon formation and
      Y chromosome loss following bone marrow transplantation and secondary
      inflammation.
AB  - Cell fusion is one mechanism by which bone marrow-derived cells (BMDCs) take on
      the gene expression pattern of nonhematopoietic cells. This process occurs in a
      number of organs with postengraftment injury but has never been found in the
      lung. We performed bone marrow (BM) transplant in a murine model of lung
      inflammation to test whether transplanted BMDCs develop lung-specific gene
      expression by fusing with diseased pneumocytes. Mice lacking the lung-specific
      protein surfactant protein C (Sp-C) were lethally irradiated, transplanted with
      sex mismatched wild-type marrow, and sacrificed 6 months later. Nineteen/38
      recipients exhibited Sp-C mRNA (RT-PCR) and/or protein (mean 0.95+/-1.18 Sp-C+
      cells per 1000 type II pneumocytes by confocal microscopy). In male recipients of
      female BM, 65% of Sp-C + cells contained the Y chromosome, indicating their
      origin from fusion. Only 28% of Sp-C+ cells in female recipients of male BMDCs
      contained the Y chromosome, suggesting that 72% of Sp-C-expressing cells lost the
      Y chromosome. In the setting of post-transplant inflammation, pneumocyte-specific
      reprogramming of transplanted BMDCs predominantly derives from heterokaryon
      formation. This process does not reverse inflammation caused by Sp-C deficiency;
      nevertheless, further investigation may identify phenotypes benefiting from such
      an approach.

PMID- 17449723
TI  - The Troll in Toll: Mal and Tram as bridges for TLR2 and TLR4 signaling.
AB  - Signaling by two of the most important bacteria-sensing TLRs, TLR2 and TLR4,
      involves two adaptor proteins, MyD88 adaptor-like (Mal) and Toll/IL-1 receptor
      (TIR) domain-containing adaptor-inducing IFN-beta (Trif)-related adaptor molecule
      (TRAM). Recently, new insights into the functioning of these two adapters have
      emerged. Mal is required by both TLRs to act as a bridge to recruit the adaptor
      MyD88, leading ultimately to NF-kappaB activation. Similarly, TRAM acts as a
      bridge to recruit TRIF to the TLR4 complex, leading to activation of the
      transcription factor IFN regulatory factor 3. Consistent with Mal and TRAM being
      key points of control, recent evidence suggests that they are subject to
      regulation by phosphorylation. Further, a variant in Mal in humans has been found
      to protect against multiple infectious diseases. Finally, another TIR domain
      containing adaptor, sterile alpha and HEAT/armadillo motif protein (SARM), has
      been shown to act as an inhibitor of TRIF-dependent signaling. These recent
      discoveries add to the complexity of TLR signaling and highlight specific control
      mechanisms for TLR2 and TLR4 signaling.

PMID- 17449724
TI  - Expression of human GITRL on myeloid dendritic cells enhances their
      immunostimulatory function but does not abrogate the suppressive effect of
      CD4+CD25+ regulatory T cells.
AB  - CD4(+)CD25(+) regulatory T cells (Treg) have been described as an important
      hurdle for immunotherapy. Engagement of glucocorticoid-induced TNF receptor
      related protein (GITR) has emerged recently as an important mechanism to control
      the suppression of CD4(+)CD25(+) Treg. Furthermore, it has been documented
      extensively that GITR ligation is costimulatory for naive and activated T cells
      in the murine setting. However, little is known about the role of the human GITR
      ligand (huGITRL). We wanted to explore whether huGITRL could enhance antigen
      specific T cell priming by dendritic cells (DC). First, we confirmed the
      endogenous expression of GITRL on HUVEC. We also detected GITRL expression on EBV
      B cell lines, whereas no GITRL expression was observed on human monocyte-derived
      DC. Electroporation of GITRL mRNA in monocyte-derived DC resulted in a strong and
      long-lasting surface expression of GITRL. In contrast to data obtained in mice,
      no significant abrogation of Treg suppression by GITRL-expressing human DC was
      observed. Consistent with our mouse data, we showed that huGITRL is costimulatory
      for responder T cells. Furthermore, we found that GITRL-expressing DC primed
      increased numbers of Melan-A-specific CD8(+) T cells. We conclude that although
      huGITRL is not capable of alleviating Treg suppression of responder T cells,
      huGITRL overexpression on monocyte-derived DC enhances their capacity to induce
      antigen-specific T cell responses. Thus, GITRL incorporation in DC might improve
      the antitumor immune response after vaccination.

PMID- 17449725
TI  - Leishmania major induces distinct neutrophil phenotypes in mice that are
      resistant or susceptible to infection.
AB  - Polymorphonuclear neutrophils (PMN) are key components of the inflammatory
      response contributing to the development of pathogen-specific immune responses.
      Following infection with Leishmania major, neutrophils are recruited within hours
      to the site of parasite inoculation. C57BL/6 mice are resistant to infection, and
      BALB/c mice are susceptible to infection, developing unhealing, inflammatory
      lesions. In this report, we investigated the expression of cell surface
      integrins, TLRs, and the secretion of immunomodulatory cytokines by PMN of both
      strains of mice, in response to infection with L. major. The parasite was shown
      to induce CD49d expression in BALB/c-inflammatory PMN, and expression of CD49d
      remained at basal levels in C57BL/6 PMN. Equally high levels of CD11b were
      expressed on PMN from both strains. In response to L. major infection, the levels
      of TLR2, TLR7, and TLR9 mRNA were significantly higher in C57BL/6 than in BALB/c
      PMN. C57BL/6 PMN secreted biologically active IL-12p70 and IL-10. In contrast, L.
      major-infected BALB/c PMN transcribed and secreted high levels of IL-12p40 but
      did not secrete biologically active IL-12p70. Furthermore, IL-12p40 was shown not
      to associate with IL-23 p19 but formed IL-12p40 homodimers with inhibitory
      activity. No IL-10 was secreted by BALB/c PMN. Thus, following infection with L.
      major, in C57BL/6 mice, PMN could constitute one of the earliest sources of IL
      12, and in BALB/c mice, secretion of IL-12p40 could contribute to impaired, early
      IL-12 signaling. These distinct PMN phenotypes may thus influence the development
      of L. major-specific immune response.

PMID- 17449726
TI  - A family of poly(U) polymerases.
AB  - The GLD-2 family of poly(A) polymerases add successive AMP monomers to the 3' end
      of specific RNAs, forming a poly(A) tail. Here, we identify a new group of GLD-2
      related nucleotidyl transferases from Arabidopsis, Schizosaccharomyces pombe,
      Caenorhabditis elegans, and humans. Like GLD-2, these enzymes are template
      independent and add nucleotides to the 3' end of an RNA substrate. However, these
      new enzymes, which we refer to as poly(U) polymerases, add poly(U) rather than
      poly(A) to their RNA substrates.

PMID- 17449727
TI  - Characterization of a cyanobacterial RNase P ribozyme recognition motif in the
      IRES of foot-and-mouth disease virus reveals a unique structural element.
AB  - Translation initiation driven by internal ribosome entry site (IRES) elements is
      dependent on the structural organization of the IRES region. Picornavirus IRES
      are organized in structural domains, in which the terminal stem-loops participate
      in functional RNA-protein interactions. However, the mechanistic role performed
      by the central domain during internal initiation has not been elucidated yet.
      Here we show that the foot-and-mouth-disease virus IRES contains a structural
      motif that serves in vitro as substrate for the Synechocystis sp. RNase P
      ribozyme, a structure-dependent endonuclease that participates in tRNA precursor
      processing. Recognition of the IRES substrate was dose dependent, required high
      magnesium concentration, and resulted in the formation of cleavage products with
      5' phosphate and 3' hydroxyl ends. Mapping of the core recognition motif
      indicated that it overlapped with the apical region of the central domain. Two
      IRES constructs containing nucleotide substitutions in the apical region of the
      central domain that reorganized RNA structure displayed an altered pattern of
      cleavage by the cyanobacterial ribozyme generating new cleavage events in nearby
      residues. From these data it is inferred that the central domain of the IRES
      region has evolved a tRNA structural mimicry that renders it a substrate for
      RNase P ribozyme reaction. Recognition of this motif was affected in defective
      IRES mutants with a local RNA structure reorganization, suggesting that its
      structural preservation is required for IRES activity.

PMID- 17449728
TI  - The 51-63 base pair of tRNA confers specificity for binding by EF-Tu.
AB  - Elongation factor Tu (EF-Tu) exhibits significant specificity for the different
      elongator tRNA bodies in order to offset its variable affinity to the esterified
      amino acid. Three X-ray cocrystal structures reveal that while most of the
      contacts with the protein involve the phosphodiester backbone of tRNA, a single
      hydrogen bond is observed between the Glu390 and the amino group of a guanine in
      the 51-63 base pair in the T-stem of tRNA. Here we show that the Glu390Ala
      mutation of Thermus thermophilus EF-Tu selectively destabilizes binding of those
      tRNAs containing a guanine at either position 51 or 63 and that mutagenesis of
      the 51-63 base pair in several tRNAs modulates their binding affinities to EF-Tu.
      A comparison of Escherichia coli tRNA sequences suggests that this specificity
      mechanism is conserved across the bacterial domain. While this contact is an
      important specificity determinant, it is clear that others remain to be
      identified.

PMID- 17449730
TI  - Analysis of FMR1 gene expression in female premutation carriers using robust
      segmented linear regression models.
AB  - Fragile X syndrome is caused by the absence or reduction of the fragile X mental
      retardation protein (FMRP) because FMR1 gene expression is reduced. Alleles with
      repeat sizes of 55-200 are classified as premutations, and it has been
      demonstrated that FMR1 expression is elevated in the premutation range. However,
      the majority of the studies reported were performed in males. We studied FMR1
      expression in 100 female fragile X family members from the northern region of
      Spain using quantitative (fluorescence) real-time polymerase chain reaction. Of
      these 100 women, 19 had normal alleles, 19 were full mutation carriers, and 62
      were premutation carriers. After confirming differences between the three groups
      of females, and increased levels of the FMR1 transcript among premutation
      carriers, we found that the relationship between mRNA levels and repeat size is
      nonlinear. These results were obtained using a novel methodology that, based on
      the size of the CGG repeats, allows us to find out the most probable threshold
      from which the relationship between CGG repeat number and mRNA levels changes.
      Using this approach, a significant positive correlation between CGG repeats and
      total mRNA levels has been found in the premutation range <100 CGG, but this
      correlation diminishes from 100 onward. However, when correcting by the X
      inactivation ratio, mRNA levels increase as the number of CGG repeats increases,
      and this increase is highly significant over 100 CGG. We suggest that due to
      skewed X inactivation, mRNA levels tend to normalize in females when the number
      of CGG repeats increases.

PMID- 17449729
TI  - Cis-acting determinants of asymmetric, cytoplasmic RNA transport.
AB  - Asymmetric subcellular distribution of RNA is used by many organisms to establish
      cell polarity, differences in cell fate, or to sequester protein activity.
      Accurate localization of RNA requires specific sequence and/or structural
      elements in the localized RNA, as well as proteins that recognize these elements
      and link the RNA to the appropriate molecular motors. Recent advances in
      biochemistry, molecular biology, and cell imaging have enabled the identification
      of many RNA localization elements, or "zipcodes," from a variety of systems. This
      review focuses on the mechanisms by which various zipcodes direct RNA transport
      and on the known sequence/structural requirements for their recognition by
      transport complexes. Computational and experimental methods for predicting and
      identifying zipcodes are also discussed.

PMID- 17449731
TI  - Breaking pseudo-twofold symmetry in the poliovirus 3'-UTR Y-stem by restoring
      Watson-Crick base pairs.
AB  - The previously described NMR structure of a 5'-CU-3'/5'-UU-3' motif, which is
      highly conserved within the 3'-UTR Y-stem of poliovirus-like enteroviruses,
      revealed striking regularities of the local helix geometry, thus retaining the
      pseudo-twofold symmetry of the RNA helix. A mutant virus with both pyrimidine
      base pairs changed into Watson-Crick replicated as wild type, indicating the
      functional importance of this symmetry relation in viral RNA replication. Here we
      investigated the effect of changing only one of the two pyrimidine base pairs to
      Watson-Crick. We determined the NMR structures of two Y-stem variants: one
      containing the 5'-CU-3'/5'-AU-3' motif, which has been found in wild-type virus
      isolates as well, and the other containing a 5'-CU-3'/5'-UG-3' motif, which is
      not present in any enterovirus sequenced to date. Both structures show single
      pyrimidine mismatches with intercalated bases. In the 5'-CU-3'/5'-AU-3' motif a C
      U Watson-Crick-type base pair is formed that retains the pseudo-twofold symmetry,
      while in the 5'-CU-3'/5'-UG-3' motif a single asymmetric U-U mismatch breaks the
      twofold symmetry. Surprisingly, for the nonnatural variant no effect of the
      single base-pair replacement was observed on polioviral RNA replication using an
      in vitro replicon assay.

PMID- 17449732
TI  - Endovascular treatment for rupture of intrahepatic artery aneurysm in a patient
      with Behcet's syndrome.

PMID- 17449733
TI  - Monitoring treatment responses in patients with pulmonary TB using serial lung
      gallium-67 scintigraphy.
AB  - OBJECTIVE: Gallium-67 scintigraphy is more sensitive than chest radiography in a
      single concurrent detection of pulmonary tuberculosis (TB). As for inflammation,
      the intensity of pulmonary uptake of 67Ga citrate theoretically is a function of
      the inflammation level in the lung. To maximize clinical applicability of 67Ga
      scintigraphy in the evaluation of pulmonary TB, we prospectively assessed serial
      qualitative associations between intensity of the uptake of 67Ga citrate and the
      severity of lung inflammation, reflected by the burden of Mycobacterium
      tuberculosis in the sputum of patients undergoing anti-TB chemotherapy. SUBJECTS
      AND METHODS: Each enrolled patient had chest radiographic, microbiologic, 67Ga
      imaging, and semiquantitation of sputum acid-fast bacillus (AFB) assessments
      before and at the third and sixth months after receiving anti-TB chemotherapy.
      The burden of pulmonary M. tuberculosis (presumably, in proportion to the
      semiquantitation of AFB in sputum) and the intensity of 67Ga citrate uptake in
      the lung at each synchronized assessment were regarded as a paired variable. Odds
      ratios were obtained from odds (derived using generalized estimating equations)
      in favor of higher pulmonary 67Ga uptake in differing scores of semiquantitation
      of sputum AFB. Linear trend for pulmonary 67Ga citrate uptake corresponding to
      varied pulmonary M. tuberculosis burdens was assessed using contrast analysis of
      their odds ratios. RESULTS: Thirty patients (24 men and six women) with pulmonary
      TB were enrolled. Eighty-six paired semiquantitations of sputum AFB-67Ga
      scintigraphic studies were collected. Twenty-six patients were cured of their
      pulmonary TB. The pulmonary 67Ga uptake increased in proportion to the higher
      score of semiquantitation of sputum AFB (p = 0.009, for trend). CONCLUSION: In
      patients with pulmonary TB, the higher the burden of M. tuberculosis in the lung,
      the higher the intensity of pulmonary 67Ga citrate uptake. Serial 67Ga
      scintigraphy examinations are helpful in evaluations of the effectiveness of anti
      TB therapy when assessments based on chest radiography are difficult.

PMID- 17449734
TI  - Bronchial arteriovenous malformation: MDCT angiography findings.

PMID- 17449735
TI  - Respiratory bronchiolitis-associated interstitial lung disease in a nonsmoker:
      radiologic and pathologic findings.

PMID- 17449736
TI  - Aortic root catheter-directed coronary CT angiography in swine: coronary
      enhancement with minimum volume of iodinated contrast material.
AB  - OBJECTIVE: The purpose of this study was to evaluate the minimum amount of
      contrast material for coronary imaging with aortic root catheter-directed
      enhancement and 64-MDCT angiography (MDCTA). MATERIALS AND METHODS: A 64-MDCT
      scanner was used after animal institutional review board approval to study four
      swine (40-60 kg). Heart rate reduction to 65 beats per minute was achieved with
      atenolol by mouth and i.v. Cardizem. Common femoral artery access was obtained
      with a 5-French micropuncture kit and sonographic guidance. A diffusiontip (640
      side holes), 5-French pigtail catheter was positioned in the aortic root on the
      CT table with a retrofitted C-arm fluoroscopy unit and connected to an arterial
      power injector. Aortic root MDCTA (retrospective ECG gating; collimation, 0.6 mm;
      tube rotation time, 0.33 second; scanning time, 10-12 seconds; tube voltage, 120
      kVp; effective mAs, 850 mAs; pitch, 0.2; field of view, 109-123 mm; slice
      thickness and increment, 0.6 and 0.3 mm) was begun 1 second after the injection
      of 100 mL of various Visipaque (iodixanol) concentrations (10%, 20%, 30%, 40%) at
      10 mL/s. Coronary mean and peak densities, 3D maximum intensity projections, and
      4D projections were obtained. RESULTS: The mean pooled coronary attenuation
      values (H +/- SD) for the right (RCA), left anterior descending (LAD), and left
      circumflex (LCx) coronary arteries at various concentrations (10%, 20%, 30%, 40%)
      were as follows: 10% (RCA [232.6 +/- 64.0], LAD [180.4 +/- 45.1], and LCx [176.6
      +/- 56.2]); 20% (RCA [383.0 +/- 98.7], LAD [324.3 +/- 60.1], and LCx [331.8 +/-
      105.5]); 30% (RCA [441.8 +/- 137.6], LAD [401.3 +/- 125.8], and LCx [418.5 +/-
      173.0]); and 40% (RCA [717.3 +/- 377.7], LAD [573.3 +/- 233.3], and LCx [584.8 +/
      189.0]). Coronary imaging with aortic root MDCTA was feasible at all
      concentrations, and the attenuation values were statistically significantly
      greater than 250 H at 20%, 30%, and 40% (p < 0.05). The attenuation values with
      aortic root MDCTA using one fifth of the volume of contrast material are
      comparable to those currently achieved both clinically and experimentally with
      peripheral i.v. MDCTA. CONCLUSION: Aortic root MDCTA can depict the coronary
      arteries with as little as 20 mL of contrast material. This may provide an
      alternative means of coronary evaluation in patients with renal insufficiency.

PMID- 17449737
TI  - Marked lipomatous infiltration of the right ventricle: MRI findings in relation
      to arrhythmogenic right ventricular dysplasia.
AB  - OBJECTIVE: The purpose of this study was to describe the structure and function
      of the heart in the presence of marked lipomatous infiltration of the right
      ventricular wall in 13 patients referred for second opinions about fatty
      infiltration of the right ventricular wall and suspected arrhythmogenic right
      ventricular dysplasia. CONCLUSION: Lipomatous infiltration with right ventricular
      thickness > or = 6 mm on MRI but without regional or global functional
      abnormalities of the right ventricle appears to be distinct from fatty right
      ventricle associated with arrhythmogenic right ventricular dysplasia. The finding
      of right ventricular fat must be interpreted cautiously to avoid the
      pharmacologic and defibrillator intervention associated with management of
      arrhythmogenic right ventricular dysplasia.

PMID- 17449738
TI  - Congenitally corrected transposition of the great arteries: imaging with 16-MDCT.

PMID- 17449739
TI  - MDCT evaluation after closure of atrial septal defect with an Amplatzer septal
      occluder.
AB  - OBJECTIVE: The essay describes the protocol for and interpretation of MDCT scans
      in the evaluation of patients after insertion of an Amplatzer septal occluder.
      CONCLUSION: In anatomic regions that cannot be confidently evaluated with
      transthoracic echocardiography, MDCT is useful for evaluating Amplatzer septal
      occluders for protrusion, migration, and residual shunt. Radiologists should be
      familiar with the imaging protocol and interpretation.

PMID- 17449740
TI  - Cadaveric and MRI study of the musculotendinous contributions to the capsule of
      the symphysis pubis.
AB  - OBJECTIVE: The purpose of this article is to define the relations of the
      symphysis pubis and capsular tissues to the adductor and rectus abdominis soft
      tissue attachments on cadaver dissection and correlate with MRI of the anterior
      pelvis. SUBJECTS AND METHODS: Seventeen cadavers (8 males and 9 females; mean
      age, 80 years) were dissected bilaterally. Rectus abdominis and adductor muscles
      were traced to the pubis and further attachments to the pubic symphysis were
      defined. Ten asymptomatic (mean age, 17; age range, 16.5-29 years) male athletes
      underwent 1.5-T MRI of the anterior pelvis with two surface microcoils (each 42
      mm in diameter). An axial T2-weighted turbo spin-echo (TSE) sequence (TR/TE,
      2,609/106; voxel size, 0.4 mm) was obtained. Axial and sagittal 3D T1-weighted
      fast-field echo (FFE) sequences (25/4.9; voxel size, 0.3 mm) were obtained.
      Sequences were repeated incorporating fat suppression and i.v. gadolinium. The
      relation of the symphysis pubis, disk, and capsular tissues to the insertions of
      the rectus abdominis, adductor muscles, and gracilis were independently evaluated
      by two experienced radiologists blinded to all clinical details. RESULTS: In all
      17 cadaver specimens, the adductor longus and rectus abdominis attached to the
      capsule and disk of the symphysis pubis, whereas the adductor brevis had an
      attachment to the capsule in seven specimens and the gracilis in one. All
      adductor tendons attached to the pubis. In all 10 athletes, the adductor longus
      and rectus abdominis bilaterally contributed to the capsular tissues and disk.
      This was only the case for the adductor brevis in four athletes. No other tendons
      involved the capsular tissues. CONCLUSION: Cadaver and MRI findings show an
      intimate relationship between the adductor longus; rectus abdominis; and
      symphyseal cartilage, disk, and capsular tissues.

PMID- 17449741
TI  - The meniscal roots: gross anatomic correlation with 3-T MRI findings.
AB  - OBJECTIVE: The purpose of this article is to highlight the normal anatomic
      features of the meniscal roots on photographs of dissected cadaveric knee
      specimens and 3-T MR images. CONCLUSION: The meniscal roots, which are critical
      attachment sites of the medial and lateral menisci to the central tibial plateau,
      are well-visualized on intermediate-weighted, turbo spin-echo 3-T MRI and can be
      identified in proximity to the tibial insertions of the anterior and posterior
      cruciate ligaments.

PMID- 17449742
TI  - Virtual Whipple: preoperative surgical planning with volume-rendered MDCT images
      to identify arterial variants relevant to the Whipple procedure.
AB  - OBJECTIVE: The purposes of this study were to combine a thorough understanding of
      the technical aspects of the Whipple procedure with advanced rendering techniques
      by introducing a virtual Whipple procedure and to evaluate the utility of this
      new rendering technique in prediction of the arterial variants that cross the
      anticipated surgical resection plane. CONCLUSION: The virtual Whipple is a novel
      technique that follows the complex surgical steps in a Whipple procedure. Three
      dimensional reconstructed angiographic images are used to identify arterial
      variants for the surgeon as part of the preoperative radiologic assessment of
      pancreatic and ampullary tumors.

PMID- 17449743
TI  - Angiodysplasia mimicking colon cancer: colonoscopy, double contrast barium enema,
      and CT findings.

PMID- 17449744
TI  - Focal nodular hyperplasia-like nodules in alcoholic liver cirrhosis: radiologic
      pathologic correlation.
AB  - OBJECTIVE: The purpose of this study was to describe our experience with three
      patients who had pathologically proven focal nodular hyperplasia (FNH)-like
      nodules that radiologically mimicked hepatocellular carcinoma (HCC). CONCLUSION:
      FNH-like nodules may radiologically mimic HCC, appearing as hypervascular masses
      on contrast-enhanced CT images and as high-signal-intensity masses on
      superparamagnetic iron oxide-enhanced MR images. Pathologically, there is the
      presence of a high number of unpaired arteries and sinusoidal capillarization,
      which may mimic HCC. Thus, it is important to differentiate FNH-like nodules
      radiologically, pathologically, and clinically from HCC.

PMID- 17449745
TI  - Three-dimensional visualization of liver segments on contrast-enhanced
      intraoperative sonography.
AB  - OBJECTIVE: The purpose of this study was to describe a novel technique for the 3D
      visualization of a liver segment on sonography, using a second-generation
      contrast agent in a dog, that would be applicable for anatomic hepatic resection.
      CONCLUSION: After a mixture of YM454 and indigo carmine was injected into a
      portal vein branch, well-delineated 3D segmental staining was seen for
      approximately 10 minutes in harmonic mode sonography. The addition of indigo
      carmine significantly prolonged the contrast effect of YM454.

PMID- 17449746
TI  - Characterization of focal bone lesions in the axial skeleton: performance of
      planar bone scintigraphy compared with SPECT and SPECT fused with CT.
AB  - OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance
      of planar 99mTc methylene diphosphonate bone scintigraphy compared with SPECT and
      SPECT fused with CT in patients with focal bone lesions of the axial skeleton.
      SUBJECTS AND METHODS: Thirty-seven patients with 42 focal lesions of the axial
      skeleton were included in this prospective study. All patients underwent planar
      scintigraphy, SPECT through the focal lesions, and SPECT-guided CT. SPECT and CT
      images then were fused digitally. The three types of images were evaluated
      separately from one another by two experienced reviewers working to consensus.
      Visibility of the lesions, diagnostic performance, and certainty in diagnosis
      were evaluated. Performance for specific diagnoses also was evaluated.
      Histologic, MRI, and clinical follow-up findings were used as the reference
      standard. RESULTS: Visibility of the lesions was significantly better with SPECT
      than with planar scintigraphy (p < 0.0001). Sensitivity and specificity for
      differentiation of benign and malignant bone lesions were 82% and 94% for planar
      scintigraphy, 91% and 94% for SPECT, and 100% and 100% for SPECT fused with CT.
      Differences between the three methods of differentiating benign and malignant
      lesions did not reach statistical significance. Certainty in diagnosis was
      significantly higher for SPECT fused with CT than for planar scintigraphy (p =
      0.004) and SPECT (p = 0.004). A specific diagnosis was made with planar
      scintigraphy in 64% of cases, with SPECT in 86%, and with SPECT fused with CT in
      all cases. CONCLUSION: Planar scintigraphy may suffice for differentiating benign
      and malignant lesions of the axial skeleton, but SPECT fused with CT
      significantly increases certainty in diagnosis and is the best tool for making a
      specific diagnosis.

PMID- 17449747
TI  - Screening carotid sonography before elective coronary artery bypass graft
      surgery: who needs it.
AB  - OBJECTIVE: The purpose of this study was to determine whether selection criteria
      for performing carotid sonographic screening before elective coronary artery
      bypass graft surgery can decrease the number of negative examinations without
      overlooking patients with significant carotid disease. SUBJECTS AND METHODS: A
      history of peripheral vascular disease, a prior cerebrovascular event, smoking,
      diabetes, hypertension, cervical carotid disease, left main coronary disease, and
      patient sex were criteria prospectively gathered for 295 consecutive patients
      undergoing screening carotid sonography before elective coronary artery bypass
      surgery. Logistic regression modeling was used to determine if any single
      criterion or combination of criteria could be applied to decrease the number of
      screening examinations without sacrificing detection of significant (> or = 50%
      cross-sectional narrowing) carotid stenosis. RESULTS: Smoking, diabetes,
      hypertension, a previous cerebrovascular event, peripheral vascular disease, left
      main coronary artery disease, and a history of cervical carotid disease were
      associated with significant carotid disease (chi-square test) in our subject
      population. Logistic modeling showed that the probability of detecting
      significant carotid disease increases 2.98 times for each additional selection
      criterion present. Possessing at least one selection criterion would still yield
      100% examination sensitivity while increasing specificity to 30.0%. CONCLUSION:
      Selection criteria should be applied when choosing patients for carotid
      sonographic screening before elective coronary artery bypass surgery. This
      approach would decrease the number of noncontributory examinations but would have
      little effect on the detection of significant carotid stenosis in this target
      population.

PMID- 17449748
TI  - High-resolution MRI of basal cell carcinomas of the face using a microscopy coil.
AB  - OBJECTIVE: The objective of this article is to evaluate the diagnostic accuracy
      of high-resolution MRI using a microscopy surface coil to stage basal cell
      carcinomas of the face. CONCLUSION: High-resolution MRI using a microscopy
      surface coil is a promising method to determine the extension of basaliomas of
      the facial region and to exclude infiltration of bone by the tumor.

PMID- 17449749
TI  - Creating animated GIF files for electronic presentations using Photoshop.
AB  - OBJECTIVE: Our objective is to present a simple method for converting movie clips
      to animated GIFs (graphics interchange format) using Photoshop. CONCLUSION:
      Although animated GIF is a more reliable format than movie clips (e.g., AVI and
      QuickTime) for presenting dynamic data sets in PowerPoint presentations, this
      output format is not available on most radiology workstations. Therefore, many
      academic radiologists still experience the problem of incompatible codecs and
      missing file links when trying to show movie clips in their PowerPoint
      presentations. One way to resolve this issue is to convert the movie clips to
      animated GIFs. In this article, we provide a simple method for this conversion
      using Photoshop--a common software application used by radiologists.

PMID- 17449750
TI  - "eThrombosis": are radiologists at risk?

PMID- 17449751
TI  - Prevalence of right portal vein branching anomalies.

PMID- 17449752
TI  - Utility of sonography in diagnosing hepatocellular carcinoma.

PMID- 17449753
TI  - Screening for a cancer: acting on social responsibility.

PMID- 17449754
TI  - Accuracy of diagnostic procedures: has it improved over the past five decades?

PMID- 17449755
TI  - Ten principles to improve the likelihood of publication of a scientific
      manuscript.
AB  - OBJECTIVE: The objective of this article is to discuss the reasons that
      manuscripts fail to be published and to establish some principles for increasing
      the likelihood of publication. CONCLUSION: Many good manuscripts fail to be
      published because they violate a few simple rules for writing a superior journal
      article. This review presents 10 principles for increasing the likelihood of
      manuscript publication.

PMID- 17449756
TI  - The American Board of Radiology perspective on maintenance of certification: part
      IV--Practice quality improvement in diagnostic radiology.

PMID- 17449757
TI  - CT-guided intervention with low radiation dose: feasibility and experience.
AB  - OBJECTIVE: The purpose of this study was to evaluate the feasibility of
      performing CT-guided interventional procedures with a very low radiation dose.
      MATERIALS AND METHODS: We performed 291 CT-guided interventional procedures using
      a low dose of radiation. The subjects were 165 men and 126 women 22-89 years old
      with a mean age of 65 years. CT fluoroscopy was not used. The procedures were 201
      percutaneous biopsies and 90 percutaneous aspiration or drainage procedures.
      Before the procedure, images were obtained with standard mAs of 175-250 mAs. All
      subsequent CT was performed at a reduced mAs. Technical success of catheter
      placement and biopsy was calculated, and the results were compared with those of
      procedures performed over the previous 12 months with standard radiation doses.
      Patient weight, lesion size, and number of CT acquisitions needed to complete the
      procedure were recorded. RESULTS: All but three aspiration or drainage procedures
      performed at 30 mAs were successful, for a success rate of 96.7%. The technical
      success rate of biopsy performed at 30 mAs was 93.5%. In the cases of 13 patients
      undergoing biopsy, the masses were not identified with low-dose technique, and
      these procedures were completed at a higher dose. Results were independent of
      patient weight and lesion size. The technical success rate was 98% for
      percutaneous drainage performed at a standard radiation dose in the 12 months
      before introduction of the low-dose technique. The technical success rate was
      87.5% for biopsy performed at a standard radiation dose in the 12 months before
      introduction of the low-dose technique. The complication rate of the low-dose
      technique was comparable to that of the standard-dose technique. CONCLUSION: Low
      dose radiation technique using 30 mAs results in technical success for both
      catheter placement and percutaneous biopsy comparable to standard radiation dose.

PMID- 17449758
TI  - Percutaneous cryoablation of large renal masses: technical feasibility and short
      term outcome.
AB  - OBJECTIVE: This retrospective study was performed to assess the feasibility,
      safety, and short-term outcome of percutaneous cryoablation of large solid renal
      tumors. MATERIALS AND METHODS: We reviewed 40 percutaneous cryoablation
      procedures performed on 40 patients with renal tumors 3 cm in diameter or larger.
      All patients underwent cryoablation with CT monitoring. Technical success was
      defined by extension of the ice ball beyond the tumor margin and postablation
      imaging findings of no contrast enhancement in the area encompassing the original
      tumor. Complications meeting grade 3 of the National Cancer Institute Common
      Terminology Criteria for Adverse Events were recorded. RESULTS: Mean +/- SD tumor
      diameter was 4.2 +/- 1.1 cm (range, 3.0-7.2 cm). Technical success was achieved
      in 38 (95%) of 40 cryoablation procedures. There was one grade 3 adverse event
      (3% rate of significant complications). Follow-up images obtained 3 months or
      longer (mean, 9 +/- 6 months; range, 3-22 months) after ablation were available
      for 26 (65%) of the 40 patients. No local tumor recurrence or tumor progression
      was found. CONCLUSION: Percutaneous cryoablation of renal tumors measuring 3 cm
      or larger is technically feasible and relatively safe. Short-term follow-up
      results are encouraging, although long-term follow-up is necessary to assess true
      treatment efficacy.

PMID- 17449759
TI  - Long-term outcome after chemoembolization and embolization of hepatic metastatic
      lesions from neuroendocrine tumors.
AB  - OBJECTIVE: Hepatic artery chemoembolization and hepatic artery embolization (HAE)
      are accepted treatments of patients with hepatic metastasis from neuroendocrine
      tumors. Long-term outcome data are limited. We present our experience in the use
      of hepatic artery chemoembolization in the treatment of patients with hepatic
      metastasis from neuroendocrine tumors. MATERIALS AND METHODS: Forty-six patients
      with carcinoid (n = 31) or islet cell (n = 15) tumors were treated. Overall and
      progression-free survival times starting with the first treatment were
      calculated. Potential factors affecting survival, including presence of
      extrahepatic disease and resection of the primary lesion, were analyzed. Relief
      of symptoms was subjectively determined for tumors with hormonal secretion.
      RESULTS: The 46 patients underwent 93 hepatic artery chemoembolization or HAE
      sessions. The mean overall survival time for the entire group was 1,273 +/- 185
      days. The mean overall survival times for the carcinoid (1,255 +/- 163 days) and
      islet cell tumor (1,311 +/- 403 days) subgroups were similar (p = 0.66). The
      progression-free survival times for the carcinoid (602 +/- 144 days) and islet
      cell (501 +/- 107 days) tumor subgroups also were similar (p = 0.72). The
      survival time of patients without known extrahepatic metastasis (n = 18; 1,571 +/
      291 days) trended toward significance compared with that of patients with known
      extrahepatic disease (n = 26; 770 +/- 112 days; p = 0.08). Resection of the
      primary tumor in 19 of 46 patients did not affect survival (resection survival,
      1,558 +/- 400 days; nonresection survival, 1,000 +/- 179 days; p = 0.44). Twenty
      of 25 patients with hormonally active tumors had relief of symptoms after one
      cycle of treatment. The 30-day mortality was 4.3%. CONCLUSION: The overall
      survival time after hepatic artery chemoembolization or HAE among patients with
      neuroendocrine tumors is approximately 3.5 years. The progression-free survival
      time approaches 1.5 years. The presence of extrahepatic metastasis or an
      unresected primary tumor should not limit the use of hepatic artery
      chemoembolization or HAE.

PMID- 17449760
TI  - Evaluation of imaging-guided core biopsy of pelvic masses.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy and
      complications of imaging-guided core biopsy in the diagnosis of pelvic masses.
      CONCLUSION: Imaging-guided core biopsy of pelvic masses is accurate and safe. The
      accuracy and sensitivity of biopsy under sonographic guidance are higher than
      those of CT-guided biopsy, although the difference is not statistically
      significant.

PMID- 17449761
TI  - Microwave ablation of renal parenchymal tumors before nephrectomy: phase I study.
AB  - OBJECTIVE: The purpose of this study was to determine, in renal neoplasms, the
      size of ablation zones induced in vivo with percutaneous microwave probes and
      whether skip areas remain within the ablation zones. CONCLUSION: For a single 10
      minute ablation, ablated volumes averaged 27 cm3 and 105 cm3 with a single-probe
      and a three-probe ablation array, respectively. There were no skip areas within
      the ablated zone. Microwave ablation can safely and quickly generate large
      ablation lesions and renal neoplasms.

PMID- 17449762
TI  - Power-pulse spray thrombectomy for treatment of Paget-Schroetter syndrome.
AB  - OBJECTIVE: This initial single-center study describes three cases of axillary
      subclavian vein thrombosis (Paget-Schroetter syndrome) treated with a rapid,
      novel thrombectomy technique, termed "power-pulse spray thrombectomy," in which a
      thrombolytic agent is directly infused into the clot via a catheter, followed by
      intravascular mechanical clot fracture and removal. CONCLUSION: All patients in
      this series were treated in a single session. Complete clot removal was
      successfully achieved without the development of any complications. This is the
      first description of the application of this technique in the treatment of Paget
      Schroetter syndrome to our knowledge.

PMID- 17449763
TI  - Complications of cervical selective nerve root blocks performed with fluoroscopic
      guidance.

PMID- 17449764
TI  - Integrated PET/CT of pulmonary neuroendocrine tumors: diagnostic and prognostic
      implications.
AB  - OBJECTIVE: The purpose of this study was to describe retrospectively integrated
      PET/CT findings on pulmonary neuroendocrine tumors and to correlate the findings
      with prognosis. MATERIALS AND METHODS: Between May 2003 and February 2005, 37
      consecutively enrolled patients (33 men and four women; mean age, 60 years) with
      histopathologically proven pulmonary neuroendocrine tumors underwent 18F-FDG
      PET/CT after enhanced standalone CT. CT was used to analyze the morphologic
      features of the tumors and PET to measure maximum standardized uptake value
      (SUV). Maximum SUVs of carcinoid tumors, large-cell neuroendocrine carcinomas
      (LCNECs), and small-cell lung carcinomas (SCLCs) were compared, and maximum SUV
      and tumor stage and prognosis were correlated. RESULTS: Four (two typical and two
      atypical) of the seven carcinoid tumors had no FDG uptake or less than
      mediastinal uptake. The maximum SUVs of primary tumors, in increasing order, were
      significantly different for carcinoids (mean, 4.0; median, 3.4), LCNECs (mean,
      12.0; median, 10.7), and SCLCs (mean, 11.6; median, 11.7) (p = 0.006, Kruskal
      Wallis test). There was no significant correlation between maximum SUV of the
      primary tumor and the tumor stages of carcinoids, LCNECs, or SCLCs (p = 0.08,
      Jonckheere-Terpstra test; p = 0.768, Mann-Whitney test). Results of receiver
      operating characteristics analysis showed a maximum SUV greater than 13.7
      suggested a poor survival period in cases of LCNEC and SCLC. CONCLUSION: The
      maximum SUVs of neuroendocrine tumors are significantly different for carcinoid
      tumors, LCNECs, and SCLCs, and a high maximum SUV suggests short survival of
      patients with LCNEC or SCLC.

PMID- 17449765
TI  - High-resolution CT of patients with primary ciliary dyskinesia.
AB  - OBJECTIVE: High-resolution CT is an important tool in the detection and
      management of bronchiectasis, but there is little information about high
      resolution CT findings in primary ciliary dyskinesia (PCD). We analyzed all high
      resolution CT studies of the chest available for a cohort of PCD patients to
      identify an associated pattern of high-resolution CT changes. MATERIALS AND
      METHODS: High-resolution CT studies were available for 45 PCD patients from 42
      families with ranges of age and disease severity. The images were assessed for
      severity and distribution of bronchiectasis, peribronchial thickening, mucous
      plugging, and other findings. A bronchiectasis severity score was calculated. CT
      findings were correlated with phenotypic findings, including situs type, ciliary
      ultrastructural defect, nasal level of nitric oxide, forced expiratory volume in
      1 second, and microbiologic findings in the airways. RESULTS: Twenty-nine adults
      (mean age, 42 +/- 15 years; age range, 21-73 years) and 16 children (mean age, 8
      +/- 4 years; age range, 1-14 years) were included; 26 (58%) of the patients were
      women or girls. Situs inversus totalis (38%) or heterotaxy (18%) was identified
      in 56% of the patients. A high (9%) prevalence of pectus excavatum was
      identified. High-resolution CT of all of the adult and 56% of the pediatric
      patients showed bronchiectasis in a predominantly middle and lower lobe
      distribution. The right middle lobe was most commonly involved. Bronchiectasis
      severity score correlated with older age and worse pulmonary function.
      CONCLUSION: High-resolution CT shows that pulmonary disease related to PCD
      predominantly involves the middle and lower lobes of the lungs. In adults, high
      resolution CT findings negative for bronchiectasis may have a role in excluding
      the diagnosis of PCD. Correlation of severity of disease on high-resolution CT
      with patient phenotype gives further insight into the diversity and natural
      history of PCD.

PMID- 17449766
TI  - Multiprojection correlation imaging for improved detection of pulmonary nodules.
AB  - OBJECTIVE: The purpose of this study was the development and preliminary
      evaluation of multiprojection correlation imaging with 3D computer-aided
      detection (CAD) on chest radiographs for cost- and dose-effective improvement of
      early detection of pulmonary nodules. SUBJECTS AND METHODS: Digital chest
      radiographs of 10 configurations of a chest phantom and of seven human subjects
      were acquired in multiple angular projections with an acquisition time of 11
      seconds (single breath-hold) and total exposure comparable with that of a
      posteroanterior chest radiograph. An initial 2D CAD algorithm with two difference
      of-gaussians filters and multilevel thresholds was developed with an independent
      database of 44 single-view chest radiographs with confirmed lesions. This 2D CAD
      algorithm was used on each projection image to find likely suspect nodules. The
      CAD outputs were reconstructed in 3D, reinforcing signals associated with true
      nodules while simultaneously decreasing false-positive findings produced by
      overlapping anatomic features. The performance of correlation imaging was tested
      on two to 15 projection images. RESULTS: Optimum performance of correlation
      imaging was attained when nine projection images were used. Compared with
      conventional, single-view CAD, correlation imaging decreased as much as 79% the
      frequency of false-positive findings in phantom cases at a sensitivity level of
      65%. The corresponding reduction in false-positive findings in the cases of human
      subjects was 78%. CONCLUSION: Although limited by a relatively simple CAD
      implementation and a small number of cases, the findings suggest that correlation
      imaging performs substantially better than single-view CAD and may greatly
      enhance identification of subtle solitary pulmonary nodules on chest radiographs.

PMID- 17449767
TI  - Time-resolved MR angiography: a primary screening examination of patients with
      suspected pulmonary embolism and contraindications to administration of iodinated
      contrast material.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficiency and
      reproducibility of a single-breath-hold time-resolved 3D MR angiographic
      technique in the diagnosis of pulmonary embolism. MATERIAL AND METHODS: Twenty
      seven consecutively registered patients with clinically suspected pulmonary
      embolism and contraindication to administration of iodinated contrast agents
      underwent imaging by time-resolved 3D MR angiography at 1.5 T. Bolus timing was
      not required. Two reviewers independently analyzed MR angiograms for overall
      image quality and evidence of pulmonary embolism. Additional imaging techniques,
      including pulmonary embolism CT angiography, ventilation-perfusion (V/Q) lung
      scanning, venous duplex sonography for deep venous thrombosis, and
      echocardiography for right ventricular strain, and 30-day and 3-month clinical
      follow-up were used to confirm the MR angiographic findings. RESULTS: Image
      quality was sufficient for diagnosis in the cases of 98% of lobar, 92-93% of
      segmental, and 94-95% of all vessel parts from the main pulmonary artery though
      the segmental branches with excellent interobserver agreement. Findings on MR
      angiography were concordant with the anatomic distribution of abnormalities for
      all pulmonary embolism CT angiographic examinations (n = 2) and four of seven V/Q
      lung scans. Screening with time-resolved 3D MR angiography allowed confident
      exclusion or inclusion of pulmonary embolism in 96% of patients. CONCLUSION: Time
      resolved 3D MR angiography provides high temporal resolution (nine phases, one
      phase per 3.3 seconds) and consistently yields arterial phase only images. As
      found with clinical follow-up, confident diagnosis of pulmonary embolism from the
      main pulmonary artery through the segmental branches can be incorporated into a
      clinical service as a screening examination of patients with contraindications to
      the use of iodinated contrast material.

PMID- 17449768
TI  - How I do it: CT pulmonary angiography.
AB  - OBJECTIVE: The purpose of this article is to describe the techniques to improve
      motion artifacts, vascular enhancement, flow artifacts, body habitus image noise,
      vascular opacification in parenchymal lung disease, streak artifacts, and the
      indeterminate CT pulmonary angiogram. In addition, this article will illustrate
      the diagnostic criteria of acute and chronic pulmonary emboli. CONCLUSION:
      Pulmonary embolism is the third most common acute cardiovascular disease, after
      myocardial infarction and stroke, and it leads to thousands of deaths each year
      because it often goes undetected. For the more than 25 years that the direct
      signs of pulmonary embolism have been available to the radiologist on CT, this
      noninvasive technique has produced a paradigm shift that has raised the standard
      of care for patients with this disease.

PMID- 17449769
TI  - MDCT detection of mitral valve calcification: prevalence and clinical relevance
      compared with echocardiography.
AB  - OBJECTIVE: The purpose of this study was to analyze the prevalence and clinical
      significance of mitral valve calcification incidentally detected on chest CT
      scans in comparison with echocardiography. MATERIALS AND METHODS: The data of 390
      patients (227 men and 163 women; mean age, 62.4 +/- 12.2 years) who underwent
      MDCT of the chest and echocardiography were retrospectively evaluated. On MDCT,
      mitral valve leaflet and annulus calcification were visually graded on a scale of
      0-3, with grade 0 denoting no calcification and grade 3 indicating severe
      calcification. CT findings were correlated with hemodynamic data obtained at
      echocardiography. Unpaired Student's t tests, chi-square analysis, and a weighted
      kappa test were used to compare results. RESULTS: In 32 (8.2%) of 390 patients,
      chest MDCT revealed mitral valve leaflet calcification. Fifteen of these patients
      (15/390, 3.8%) presented with mitral valve stenosis. Excellent agreement (kappa =
      0.882) was seen between the presence of mitral valve calcification on MDCT and
      echocardiographically proven mitral valve sclerosis. Mitral valve leaflet
      calcification on MDCT and the severity of mitral valve disease on
      echocardiography showed a substantial agreement (kappa = 0.730). A significant
      relationship was seen between the degree of mitral valve calcification on MDCT
      and the echocardiographically determined severity of mitral valve disease (no
      sclerosis vs mitral sclerosis vs mitral stenosis; p < 0.0001). CONCLUSION: Mitral
      valve leaflet calcification on MDCT indicates mitral valve sclerosis or stenosis.
      Thus, patients presenting with incidentally detected mitral valve leaflet
      calcification on chest CT may benefit from a functional assessment with
      echocardiography.

PMID- 17449770
TI  - CT appearance of thoracic aortic graft complications.
AB  - OBJECTIVE: The purpose of this study was to document the spectrum of CT findings
      and the clinical outcome of thoracic aortic graft complications. CONCLUSION:
      Aortic graft complications detected with CT may or may not be clinically apparent
      and/or relevant. CT characterization in combination with clinical findings helps
      to determine patient treatment.

PMID- 17449771
TI  - Wrist ligament tears: evaluation of MRI and combined MDCT and MR arthrography.
AB  - OBJECTIVE: The purpose of this study was to evaluate the performance of MRI and a
      combination of MDCT arthrography and MR arthrography in the diagnosis of tears
      and cartilage abnormalities of the wrist ligaments. SUBJECTS AND METHODS: The
      feasibility of combining MDCT arthrography and MR arthrography and performing
      them with an optimized contrast solution was evaluated in vitro and in vivo.
      Forty-five consecutively enrolled subjects with suspected wrist ligament tears
      underwent MRI and a combined MDCT and MR arthrographic procedure. Two observers
      reviewed the images for evidence of tears and cartilage abnormalities of the
      scapholunate and lunotriquetral ligaments and triangular fibrocartilaginous
      complex. Interobserver agreement was determined with kappa statistics, and the
      diagnostic accuracy of each technique was calculated. RESULTS: A 1:1 solution of
      2.5 mmol/L tetraazacyclododecanetetraacetic acid (DOTA)-gadolinium and 300 mg
      I/mL iopamidol provided adequate contrast enhancement for both in vitro and in
      vivo MDCT arthrographic and MR arthrographic images. Interobserver agreement was
      substantial for MRI (kappa = 0.61) and MR arthrography (kappa = 0.71) and almost
      perfect for MDCT arthrography (kappa = 0.93). The sensitivity and specificity of
      MRI, MDCT arthrography, and MR arthrography for tears of the scapholunate
      ligament were 59% and 70%, 95% and 96%, and 68% and 87% for the first observer
      and 77% and 83%, 95% and 100%, and 77% and 87% for the second observer. For tears
      of the lunotriquetral ligament, these values were 30% and 94%, 100% and 94%, and
      60% and 97% for the first observer and 50% and 97%, 90% and 100%, and 50% and 94%
      for the second observer. The three techniques appeared equivalent for complete
      tears of the scapholunate and lunotriquetral ligaments, but partial tears were
      significantly better visualized with MDCT arthrography. The sensitivity and
      specificity of MRI, MDCT arthrography, and MR arthrography for triangular
      fibrocartilaginous complex tears were 27% and 100%, 100% and 100%, and 82% and
      100% for the first observer and 45% and 100%, 100% and 100%, and 82% and 100% for
      the second observer. For cartilage abnormalities, these values were 30% and 100%,
      100% and 100%, and 30% and 100% for the first observer and 10% and 100%, 100% and
      100%, and 40% and 100% for the second observer. CONCLUSION: MDCT arthrography
      appears more accurate than MRI and MR arthrography, particularly for discerning
      partial tears of the scapholunate and lunotriquetral ligaments that do not
      necessitate surgical therapy.

PMID- 17449772
TI  - Isotropic MRI of the knee with 3D fast spin-echo extended echo-train acquisition
      (XETA): initial experience.
AB  - OBJECTIVE: The purpose of our study was to prospectively compare a recently
      developed method of isotropic 3D fast spin-echo (FSE) with extended echo-train
      acquisition (XETA) with 2D FSE and 2D fast recovery FSE (FRFSE) for MRI of the
      knee. SUBJECTS AND METHODS: Institutional review board approval, Health Insurance
      Portability and Accounting Act (HIPAA) compliance, and informed consent were
      obtained. We studied 10 healthy volunteers and one volunteer with knee pain using
      3D FSE XETA, 2D FSE, and 2D FRFSE. Images were obtained both with and without fat
      suppression. Cartilage and muscle signal-to-noise ratio (SNR) and cartilage-fluid
      contrast-to-noise ratio (CNR) were compared using a Student's t test. We also
      compared reformations of 3D FSE XETA with 2D FSE images directly acquired in the
      axial plane. RESULTS: Cartilage SNR was higher with 3D FSE XETA (56.8 +/- 9 [SD])
      compared with the 2D FSE (45.8 +/- 8, p < 0.01) and 2D FRFSE (32.5 +/- 5.3, p <
      0.01). Muscle SNR was significantly higher with 3D FSE XETA (52.1 +/- 4.3) than
      2D FSE (45.2 +/- 9, p < 0.01) and 2D FRFSE (23.6 +/- 6.2, p < 0.01). Fluid SNR
      was significantly higher for 2D FSE (144.9 +/- 33) than 3D FSE XETA (104.7 +/-
      18, p < 0.01). Compared with 2D FSE and 2D FRFSE, 3D FSE XETA had lower cartilage
      fluid CNR due to higher cartilage SNR (p < 0.01). Three-dimensional FSE XETA
      acquired volumetric data sets with isotropic resolution. Reformatted images in
      the axial plane were similar to axial 2D FSE acquisitions but with thinner
      slices. CONCLUSION: Three-dimensional FSE XETA acquires high-resolution
      (approximately 0.7 mm) isotropic data with intermediate and T2-weighting that may
      be reformatted in arbitrary planes. Three-dimensional FSE XETA is a promising
      technique for MRI of the knee.

PMID- 17449773
TI  - Volumetric quantitative CT of the spine and hip derived from contrast-enhanced
      MDCT: conversion factors.
AB  - OBJECTIVE: The purposes of this study were to perform volumetric quantitative CT
      (QCT) of the spine and hip using nondedicated contrast-enhanced standard MDCT
      data sets and to derive a conversion factor for bone mineral density (BMD)
      assessment based on dedicated volumetric QCT data sets. SUBJECTS AND METHODS:
      Forty postmenopausal women with a mean +/- SD age of 71 +/- 9 years underwent
      routine contrast-enhanced abdominal and pelvic MDCT. Before this imaging
      examination, standard volumetric QCT of the spine (L1-L3, n = 40) and hip (n =
      21) was performed. Relations between QCT and contrast-enhanced MDCT findings were
      assessed with linear regression analysis. RESULTS: Mean lumbar BMD was 84.1 +/-
      35.8 mg/mL, and mean femoral BMD was 0.62 +/- 0.12 g/cm2, as determined with QCT.
      Contrast-enhancement values with MDCT were on average 30.3% higher than those of
      QCT in the spine and 2.3% higher in the proximal femur (p < 0.05). Based on
      linear regression, a correlation coefficient of r = 0.98 was calculated for
      lumbar BMD with the equation BMD(QCT) = 0.96xBMD(MDCT) - 20.9 mg/mL. A
      coefficient of r = 0.99 was calculated for the proximal femur with the equation
      BMD(QCT) = 0.99xBMD(MDCT) - 12 mg/cm2 (p < 0.01). In 17 of 40 patients, 33
      vertebral fractures were found. The dedicated QCT and enhanced MDCT data sets did
      not show a significant difference (p > 0.05) between patients with fractures and
      those without fractures. CONCLUSION: With the conversion factors, reliable
      volumetric BMD measurements can be calculated for the hip and the spine from
      routine abdominal and pelvic MDCT data sets.

PMID- 17449774
TI  - Acral myxoinflammatory fibroblastic sarcomas: MRI findings in four cases.
AB  - OBJECTIVE: Acral myxoinflammatory fibroblastic sarcoma is a rare, recently
      described, low-grade sarcoma that involves mainly the distal extremities. The
      purpose of this study is to report the MRI findings in four cases of acral
      myxoinflammatory fibroblastic sarcoma. CONCLUSION: Acral myxoinflammatory
      fibroblastic sarcomas may present with various MRI patterns that probably reflect
      their variable histologic composition. Differential diagnosis with other benign
      conditions, especially with ganglion cysts and giant cell tumors of the tendon
      sheath, may be difficult. We report tumoral invasion of the bone in one case,
      which to our knowledge has not been previously described.

PMID- 17449775
TI  - Comparison of CT methods for determining the fat content of the liver.
AB  - OBJECTIVE: The purpose of this study was to assess which of a number of methods
      of measuring attenuation on CT scans is best for prediction of hepatic fat
      content. MATERIALS AND METHODS: This retrospective study was approved by our
      institutional review board. Consecutively registered patients who underwent liver
      resection for metastatic disease formed the study group. Attenuation measurements
      were obtained from 12 regions of interest in the liver and three in the spleen on
      both unenhanced and portal phase contrast-enhanced preoperative hepatic CT
      images. Hepatic attenuation measurements were analyzed both with and without
      normalization with the spleen. Normalization included both differences and ratios
      between hepatic and splenic attenuation values. Pathologic fat content was graded
      semiquantitatively as a percentage of the nonneoplastic liver parenchyma of the
      resected specimen. Average attenuation values of the liver were compared with
      pathologic fat content, as were the differences and ratios between hepatic and
      splenic attenuation values. Linear regression analysis was conducted on a log-log
      scale. RESULTS: Data on 88 patients were analyzed. On unenhanced and contrast
      enhanced CT images, all associations between pathologic fat content and
      attenuation measurements were significant (p < 0.0001). All series of R2 values
      for unenhanced CT scans were much higher than those for contrast-enhanced CT
      scans. The R2 values of liver-only measurement were higher than those of hepatic
      values normalized with splenic values on both unenhanced (0.646-0.649 > 0.523,
      0.565) and contrast-enhanced (0.516 > 0.242, 0.344) CT. CONCLUSION: Measurement
      of attenuation of liver only on unenhanced CT scans is best for prediction of
      pathologic fat content.

PMID- 17449776
TI  - New CT criterion for acute appendicitis: maximum depth of intraluminal
      appendiceal fluid.
AB  - OBJECTIVE: The purpose of this study was to evaluate whether a new criterion
      maximum depth of the intraluminal appendiceal fluid-is useful to differentiate
      between a normal appendix with diameter greater than 6 mm and appendicitis
      without periappendiceal inflammation. MATERIALS AND METHODS: The study included
      59 patients showing a normal appendix with diameter greater than 6 mm and having
      no adjacent lesions (noncomplicated-normal-appendix group), 30 patients showing a
      normal appendix with diameter greater than 6 mm and having adjacent lesions
      (complicated-normal-appendix group), and 38 patients showing appendicitis without
      periappendiceal inflammation (appendicitis group). The following specific CT
      findings were retrospectively evaluated: maximum appendiceal diameter greater
      than 6 mm, maximum appendiceal wall thickness greater than 3 mm, appendiceal wall
      enhancement, focal cecal wall thickening, adjacent adenopathy, appendicolith, and
      maximum depth of the intraluminal appendiceal fluid. RESULTS: The mean maximum
      depth of the intraluminal appendiceal fluid in the appendicitis group was
      significantly higher than in the two groups with a normal appendix (Mann-Whitney
      U test: p < 0.001). When using maximum depth of the intraluminal appendiceal
      fluid greater than 2.6 mm for a criterion of appendicitis, sensitivity and
      specificity for differentiation between the appendicitis group and the other two
      groups with a normal appendix were both greater than 80%. In contrast, when using
      another CT a criterion, either sensitivity or specificity was 50% or less.
      CONCLUSION: The new CT criterion based on the maximum depth of the intraluminal
      appendiceal fluid greater than 2.6 mm is particularly useful for differentiating
      appendicitis without periappendiceal inflammation from a normal appendix with a
      diameter greater than 6 mm.

PMID- 17449777
TI  - Enhancing and expansile portal vein thrombosis: value in the diagnosis of
      hepatocellular carcinoma in patients with multiple hepatic lesions.
AB  - OBJECTIVE: The objective of this study was to determine whether the presence of
      enhancing and expansile portal vein thrombus is suggestive of the diagnosis of
      hepatocellular carcinoma. CONCLUSION: In the presence of hepatic tumors,
      enhancing expansile portal vein thrombus is highly suggestive of hepatocellular
      carcinoma.

PMID- 17449778
TI  - CT criteria for differentiating abdominal hemorrhage: anticoagulation or aortic
      aneurysm rupture?
AB  - OBJECTIVE: The purpose of our study was to test the hypothesis that CT criteria
      would allow accurate diagnosis of the specific cause of abdominal hemorrhage in
      patients with coagulopathy or abdominal aortic aneurysm. CONCLUSION: Attention to
      specific CT criteria allows accurate diagnosis of the specific cause of
      spontaneous abdominal hemorrhage even in patients who have both coagulopathy and
      an abdominal aortic aneurysm.

PMID- 17449779
TI  - Validation of metal oxide semiconductor field effect transistor technology for
      organ dose assessment during CT: comparison with thermoluminescent dosimetry.
AB  - OBJECTIVE: The purposes of this study were to apply near-real-time dose
      measurement technology with metal oxide semiconductor field effect transistors
      (MOSFETs) to the assessment of organ dose during CT and to validate the method in
      comparison with the thermoluminescent dosimeter (TLD) method. MATERIALS AND
      METHODS: Dosimetry measurements were performed in two ways, one with TLDs and the
      other with MOSFETs. Twenty organ locations were selected in an adult
      anthropomorphic female phantom. High-sensitivity MOSFET dosimeters were used. For
      the reference standard, TLDs were placed in the same organ locations as the
      MOSFETs. Both MOSFET and TLD detectors were calibrated with an X-ray beam
      equivalent in quality to that of a commercial CT scanner (half-value layer,
      approximately 7 mm Al at 120 kVp). Organ dose was determined with a scan protocol
      for pulmonary embolus studies on a 4-MDCT scanner. RESULTS: Measurements for
      selected organ doses and the percentage difference for TLDs and MOSFETs,
      respectively, were as follows: thyroid (0.34 cGy, 0.31 cGy, -8%), middle lobe of
      lung (2.4 cGy, 3.0 cGy, +26%), bone marrow of thoracic spine (2.2 cGy, 2.5 cGy,
      +11%), stomach (1.0 cGy, 0.93 cGy, -6%), liver (2.5 cGy, 2.6 cGy, +6%), and left
      breast (3.0 cGy, 2.9 cGy, -1%). Bland-Altman analysis showed that the MOSFET
      results agreed with the TLD results (bias, 0.042). CONCLUSION: We found good
      agreement between the results with the MOSFET and TLD methods. Near-real-time CT
      organ dose assessment not previously feasible with TLDs was achieved with
      MOSFETs. MOSFET technology can be used for protocol development in the rapidly
      changing MDCT scanner environment, in which organ dose data are extremely
      limited.

PMID- 17449780
TI  - Detection of hepatocellular carcinoma on CT in liver transplant candidates:
      comparison of PACS tile and multisynchronized stack modes.
AB  - OBJECTIVE: The objective of our study was to compare CT image interpretation
      using PACS tile and multisynchronized stack modes with respect to speed and
      observer performance for the detection of hepatocellular carcinoma (HCC) in liver
      transplant candidates. MATERIALS AND METHODS: Institutional review board approval
      was obtained, but informed consent was not required for this retrospective study.
      Sixty-seven patients underwent dynamic multiphasic CT within 3 months before
      liver transplantation. Interval reviews using tile and multisynchronized stack
      modes were performed independently by four reviewers with various levels of
      experience to determine the presence of HCC using a five-point confidence scale.
      Observer performance was compared using jackknife free-response receiver
      operating characteristic (ROC) analysis. The time required to interpret the CT
      scans using each mode was recorded and compared using the paired Student's t
      test. RESULTS: Twenty-seven patients had 48 HCC nodules. The mean free-response
      ROC figures of merit for detecting HCC were significantly higher using the
      multisynchronized stack mode (0.731) than using the tile mode (0.662) (F
      statistic = 6.603, p = 0.012). The 95% CIs for the task were -0.125 - -0.016. The
      time used for image analysis was also significantly shorter with the stack mode
      (63 to approximately 75 seconds) than with the tile mode (94 to approximately 191
      seconds) for all four reviewers (p < 0.0001). CONCLUSION: Multisynchronized stack
      viewing of multiphasic dynamic CT scans significantly increases the detection
      rate of HCC in liver transplant candidates. It also significantly shortens the
      interpretation time compared with tile viewing.

PMID- 17449781
TI  - A pattern approach to the abnormal small bowel: observations at MDCT and CT
      enterography.
AB  - OBJECTIVE: Imaging of the vast array of pathologic processes occurring in the
      small bowel has been facilitated by recent advances, including the use of MDCT
      scanners that acquire isotropic data and neutral oral contrast agents that
      improve small-bowel distention. CONCLUSION: This review shows how a systematic
      pattern approach can be used to narrow the differential diagnosis when an
      abnormal small-bowel loop is detected on MDCT.

PMID- 17449782
TI  - Characteristic locations of inguinal region and anterior abdominal wall hernias:
      sonographic appearances and identification of clinical pitfalls.
AB  - OBJECTIVE: The purpose of this article is to show the typical locations of
      anterior abdominal wall and inguinal region hernias and to illustrate their
      sonographic appearances and describe pitfalls in clinical diagnosis of hernias
      that may be resolved with sonography. CONCLUSION: Awareness of the expected
      locations of anterior abdominal wall hernias and potential clinical pitfalls
      allows an accurate diagnosis of a hernia and helps in differentiating a hernia
      from other abnormalities.

PMID- 17449783
TI  - Littoral cell angioma of the spleen.

PMID- 17449784
TI  - Effect of i.v. injection of radiographic contrast media on human renal blood
      flow.
AB  - OBJECTIVE: The purpose of our study was to assess the effect of an i.v. injection
      of iodinated radiographic contrast medium on human renal blood flow using cine
      phase-contrast MRI. SUBJECTS AND METHODS: We examined 12 healthy adult
      volunteers. Blood flow in one renal artery was measured using cine phase-contrast
      imaging (1.5-T MR system). Each volunteer received 120 mL of isotonic sodium
      chloride on study day 1 and 120 mL of a low-osmolar, nonionic, iodinated contrast
      medium (iomeprol, 400 mg I/mL) on study day 2. Repetitive measurements were
      performed before (up to five measurements in 5 minutes) and after (up to 13
      measurements in 30 minutes) the injection was started. RESULTS: Mean basal renal
      artery blood flow was 664 mL/min. In response to the injection of the test
      substances, we found a significantly larger decrease in average renal blood flow
      for contrast medium than for sodium chloride (31.9 mL/min vs 18.3 mL/min, p =
      0.0481). Furthermore, in analyzing the measurements at early time points, we
      found a significant decrease (11.4% +/- 4.7% [SD]; Bonferroni-corrected, p <
      0.05) in renal blood flow 2 minutes after the injection of the contrast medium
      was started. Sodium chloride did not produce a significant effect at any time.
      CONCLUSION: Cine phase-contrast MRI can measure a decrease in renal blood flow in
      humans in response to an i.v. injection of iodinated radiographic contrast
      medium. Therefore, cine phase-contrast MRI can be a helpful and noninvasive tool
      for further investigations of contrast media-induced changes in human renal blood
      flow and their possible impact on the development of contrast-induced
      nephropathy.

PMID- 17449785
TI  - Endorectal MRI of prostatic and periprostatic cystic lesions and their mimics.

PMID- 17449786
TI  - Renal pseudotumors.
AB  - OBJECTIVE: Renal cell carcinoma is the most common malignant tumor to involve the
      kidneys; however, a number of other entities--called renal pseudotumors--may
      mimic renal neoplasms on imaging. This article presents the imaging features and
      pathologic correlation of some of the common and uncommon renal pseudomasses.
      CONCLUSION: Many renal lesions look similar to renal cell carcinoma on radiologic
      imaging. The imaging features of renal pseudotumors presented in this article
      will help radiologists to identify them and to triage these patients for
      appropriate management.

PMID- 17449787
TI  - The 2005 Australian MRI safety survey.
AB  - OBJECTIVE: The purpose of this study was to ascertain current MRI safety
      practices in Australia regarding permanent pacemakers, temporary pacing wires,
      cerebral aneurysm clips, implants of unknown MRI safety status, and use of metal
      detectors, with respect to adherence to published guidelines. MATERIALS AND
      METHODS: A questionnaire was distributed to more than 100 MRI facilities in
      Australia. RESULTS: Ninety-two responses, representing 102 MRI systems, were
      received. Respondents from approximately one in 15 sites were aware they had
      inadvertently imaged a patient who had a permanent pacemaker (eight patients).
      One of these episodes led to a death. Use of modified request forms, on which
      referring physicians are asked for MRI safety information, was incomplete (48/90
      facilities). Four facilities deliberately imaged pacemaker patients. Seventy
      seven of 89 facilities responded that they do not image patients with temporary
      pacing wires. Aneurysm clips were accepted by most sites (71/91), and only one
      site associated with a neurosurgical service refused such patients. Seventy of 71
      facilities required written identification of the clip type. Most (77/90) of the
      sites reported delays due to the unknown MRI safety status of implants. Only four
      of 92 sites reported routine use of a metal detector. The guidelines of the
      American College of Radiology and of the Royal Australian and New Zealand College
      of Radiologists were equally influential (38% each). Only 10 of 90 respondents
      reported use of external audits of safety processes. CONCLUSION: Ongoing
      vigilance is required for avoiding MRI of patients with pacemakers, particularly
      when information from the patient is unreliable or unobtainable. Requiring
      referring physicians to provide MRI safety information may help to minimize risk.

PMID- 17449788
TI  - Evaluation of two diuresis renography decision support systems to determine the
      need for furosemide in patients with suspected obstruction.
AB  - OBJECTIVE: The purpose of this study was to compare the decisions regarding the
      need for furosemide made by two independent renal decision support systems, RENEX
      and CAR-TAN, with the need for furosemide determined in clinical practice and by
      expert reviewers using the baseline plus furosemide protocol. SUBJECTS AND
      METHODS: RENEX and CARTAN are independent decision support systems that reach
      their conclusions without operator input. RENEX is a knowledge-based system and
      CARTAN is a statistical decision support system. Both were trained using the same
      pilot group of 31 adult patients (61 kidneys) referred for suspected obstruction.
      Subsequently, both systems were prospectively applied to 102 patients (200
      kidneys) of whom 70 received furosemide; decisions regarding the need for
      furosemide were compared with the clinical decisions and the decisions of three
      experts who independently scored each kidney on the need for furosemide.
      Differences were resolved by consensus. RESULTS: RENEX agreed with the clinical
      and experts' decisions to give furosemide in 97% (68/70) and 98% (65/66) of
      patients, respectively, whereas CARTAN agreed in 90% (63/70) and 89% (59/66),
      respectively, p < 0.03. In contrast, CARTAN agreed with the experts' decision to
      withhold furosemide in 78% of kidneys (87/111), whereas RENEX agreed in only 69%
      of kidneys (77/111), p = 0.008. CONCLUSION: Use of RENEX or CARTAN as decision
      support tools in the baseline plus furosemide protocol has the potential to help
      the radiologist avoid unnecessary imaging and reduce the technologist, computer,
      camera, and physician time required to perform the procedure.

PMID- 17449789
TI  - Hippocampal volume and the Mini-Mental State Examination in the diagnosis of
      amnestic mild cognitive impairment.
AB  - OBJECTIVE: The purpose of this study was to examine the diagnostic efficacy of
      hippocampal volumetry and the Mini-Mental State Examination (MMSE) in
      differentiating amnestic mild cognitive impairment from the normal changes of
      aging. SUBJECTS AND METHODS: The conditions of healthy older persons (n = 17) and
      persons with amnestic mild cognitive impairment (n = 18) were classified on the
      basis of results of comprehensive neuropsychological assessment. All subjects
      underwent MRI at 4 T, including high-resolution coronal T1-weighted images.
      Hippocampal volume was calculated by tracing right and left hippocampal
      formations on coronal slices and normalizing by single-slice intracranial area.
      Receiver operating characteristic analysis and logistic regression analysis were
      performed to evaluate the diagnostic efficacy of hippocampal volume and the MMSE
      in differentiating subjects with amnestic mild cognitive impairment from subjects
      with normal cognitive function. RESULTS: The mean +/- SE area under the receiver
      operating characteristics curve (AUC) for left hippocampal volume (0.886 +/-
      0.056) was greater than that for right hippocampal volume (0.614 +/- 0.097). The
      AUC for MMSE score (0.745 +/- 0.085) was intermediate and not statistically
      different from that of hippocampal volume measurements alone. The AUC for the
      combination of left hippocampal volume and MMSE score (0.92) was significantly
      greater than that of MMSE score alone (p < 0.05). CONCLUSION: In the diagnosis of
      amnestic mild cognitive impairment, use of left hippocampal volume may be more
      efficacious than use of right hippocampal volume and may add to the value of
      routine screening MMSE. Automated hippocampal volumetry may become a useful
      diagnostic adjunct in settings in which sophisticated neuropsychological testing
      is not readily available.

PMID- 17449790
TI  - Radiation dose reduction for augmentation mammography.
AB  - OBJECTIVE: Patients who undergo cosmetic augmentation have larger and denser
      breasts and receive higher radiation doses during mammography than women without
      implants. In this study we evaluated the dose increase and techniques for dose
      reduction. SUBJECTS AND METHODS: Mean glandular dose to the breast during
      screening mammography was measured for 206 women who had undergone breast
      augmentation. For 13 of these women, mean glandular dose from preoperative
      mammography also was measured. Effective tube current, peak kilovoltage, and
      breast thickness were measured, and mean glandular dose was calculated for 1,632
      images. Two screen-film combinations and three target-filter combinations were
      studied. RESULTS: For four-view augmentation mammography with a molybdenum
      molybdenum (Mo-Mo) target-filter combination, mean glandular dose was reduced
      35%, from 10.7 to 7.0 mGy, by changing the screen-film combination from 100 to
      190 speed. For four-view augmentation mammography, mean glandular dose was
      reduced 24% by changing the target-filter combination from Mo-Mo to rhodium
      rhodium (Rh-Rh) for full views of breasts containing implants. For four-view
      augmentation mammography, mean glandular dose was reduced 50% by changing the
      screen-film combination from 100 to 190 speed and changing the target-filter
      combination from Mo-Mo to Rh-Rh for implant-full views. CONCLUSION: Mean
      glandular dose per breast from four-view augmentation mammography with the 100
      speed screen-film and Mo-Mo target-filter combinations averaged 10.7 mGy, which
      is 3.1 times higher than the 3.4 mGy for conventional two-view mammography of
      breasts without implants. In 40 years of screening, this number represents a more
      than tripled lifetime attributable risk of radiation-induced breast cancer--an
      unacceptable level. Use of faster screen-film combinations, use of Rh-Rh target
      filter combinations, and acquisition of three rather than four views are dose
      reduction methods that together result in a 66% dose reduction, from 10.7 to 3.6
      mGy. Mean glandular dose should be kept less than 7.0 mGy per breast for
      screening mammography of patients with breast implants.

PMID- 17449791
TI  - Emergency department visits for pediatric trampoline-related injuries: an update.
AB  - OBJECTIVES: To describe the epidemiology of emergency department (ED) visits for
      trampoline-related injuries among U.S. children from January 1, 2000, to December
      31, 2005, using the National Electronic Injury Surveillance System (NEISS) and to
      compare recent trampoline injury demographics and injury characteristics with
      those previously published for 1990-1995 using the same data source. METHODS: A
      stratified probability sample of U.S. hospitals providing emergency services in
      NEISS was utilized for 2000-2005. Nonfatal trampoline-related injury visits to
      the ED were analyzed for patients from 0 to 18 years of age. RESULTS: In 2000
      2005, there was a mean of 88,563 ED visits per year for trampoline-related
      injuries among 0-18-year-olds, 95% of which occurred at home. This represents a
      significantly increased number of visits compared with 1990-1995, when there was
      an average of 41,600 visits per year. Primary diagnosis and principal body part
      affected remained similar between the two study periods. CONCLUSIONS: ED visits
      for trampoline-related injuries in 2000-2005 increased in frequency by 113% over
      the number of visits for 1990-1995. Trampoline use at home continues to be a
      significant source of childhood injury morbidity.

PMID- 17449792
TI  - U.S. emergency department visits for supraventricular tachycardia, 1993-2003.
AB  - BACKGROUND: Supraventricular tachycardia (SVT) is often described as a recurrent
      condition that leads to emergency department (ED) visits. However, the
      epidemiology of ED visits for SVT is unknown. OBJECTIVES: To define the frequency
      of SVT in U.S. EDs and to analyze patient characteristics, ED management, and
      disposition for such visits. METHODS: The authors analyzed data from the National
      Hospital Ambulatory Medical Care Survey, 1993-2003. SVT cases were identified by
      using the International Classification of Diseases, Ninth Revision, Clinical
      Modification codes 426.7 or 427.0 in any of the three diagnostic fields. RESULTS:
      Of the 1.1 billion ED visits over the 11-year study period, an estimated 555,000
      (0.05%; 95% confidence interval [CI] = 0.04% to 0.06%) were related to SVT. The
      annual frequency and population rate appear stable between 1993 and 2003 (p for
      trend = 0.35). Compared with non-SVT visits, those with SVT were more likely to
      be older than 65 years of age (26% vs. 15%, p < 0.01) and female (70% vs. 53%, p
      < 0.01). Electrocardiograms were documented for most visits (91%; 95% CI = 85% to
      96%). Approximately half of the patients (51%; 95% CI = 40% to 61%) received an
      atrioventricular nodal blocking medication, most frequently adenosine (26%; 95%
      CI = 17% to 36%). SVT visits ended in hospital admission for 24% (95% CI = 15% to
      34%). At the other extreme, 44% (95% CI = 32% to 56%) were discharged without
      planned follow-up. CONCLUSIONS: Supraventricular tachycardia accounts for
      approximately 50,000 ED visits each year. Higher visit rates in older adults and
      female patients are consistent with prior studies of SVT in the general
      population. This study provides an epidemiologic foundation that will enable
      future research to assess and improve clinical management strategies of SVT in
      the ED.

PMID- 17449793
TI  - Effect of intravenous albumin infusion on brain salicylate concentration.
AB  - BACKGROUND: Salicylate poisoning appears to result in death, despite supportive
      care, once a critical brain salicylate concentration is reached. The binding of
      salicylate to albumin is saturable; free plasma salicylate concentrations rise
      disproportionately to total drug levels. Because unbound salicylate distributes
      into the brain, the authors questioned whether an intravenous (i.v.) infusion of
      albumin would cause a redistribution of salicylate from the brain back into the
      plasma, which might allow enough time for hemodialysis to be instituted.
      OBJECTIVES: To determine if i.v. albumin infusion would lower brain salicylate
      concentrations through redistribution in a porcine model of acute salicylate
      poisoning. METHODS: In a randomized controlled trial, 17 swine under anesthesia
      and controlled ventilation received 400 mg/kg of sodium salicylate i.v. over 15
      minutes. At 60 minutes, nine animals received 1.25 g/kg albumin (25% solution)
      i.v. over 15 minutes, while eight control animals received an equal volume of
      normal saline (5 mL/kg). Arterial pH was maintained between 7.45 and 7.55. Serial
      measurements of serum albumin as well as free and total salicylate concentrations
      were obtained, and urine was collected for measurement of total salicylate
      excretion. At 180 minutes, animals were killed and brains harvested for
      measurement of brain salicylate concentrations. RESULTS: Average peak serum total
      salicylate concentrations of 105.5 and 109 mg/dL were achieved in control and
      albumin-treated animals, respectively. Albumin infusion was accompanied by
      statistically significant increases in serum total salicylate concentrations
      (median from 79.5 to 86.9 mg/dL at 75 minutes), while levels decreased slightly
      in control animals. Serum free salicylate concentrations decreased slightly in
      albumin-treated animals, but the difference was not statistically significant.
      Median brain salicylate concentrations were about 14% lower in the albumin
      treatment group (17.8 mg/100 g brain) compared with controls (20.5 mg/100 g
      brain); this approached statistical significance (p = 0.075). Median urinary
      salicylate excretion was higher in the albumin-treated group (0.83 vs. 0.48 g; p
      = 0.072), with similar urinary pH and volumes in both groups. CONCLUSIONS: In
      this animal model of salicylate poisoning, i.v. infusion of 1.25 g/kg albumin was
      accompanied by a 14% decline in median brain salicylate concentrations, which
      approached statistical significance.

PMID- 17449794
TI  - Functional coupling between the Na+/Ca2+ exchanger and nonselective cation
      channels during histamine stimulation in guinea pig tracheal smooth muscle.
AB  - Airway smooth muscle (ASM) contracts partly due to an increase in cytosolic
      Ca(2+). In this work, we found that the contraction caused by histamine depends
      on external Na(+), possibly involving nonselective cationic channels (NSCC) and
      the Na(+)/Ca(2+) exchanger (NCX). We performed various protocols using isometric
      force measurement of guinea pig tracheal rings stimulated by histamine. We
      observed that force reached 53 +/- 1% of control during external Na(+)
      substitution by N-methyl-D-glucamine(+), whereas substitution by Li(+) led to no
      significant change (91 +/- 1%). Preincubation with KB-R7943 decreased the maximal
      force developed (52.3 +/- 5.6%), whereas preincubation with nifedipine did not
      (89.7 +/- 1.8%). Also, application of the nonspecific NCX blocker KB-R7943 and
      nifedipine on histamine-precontracted tracheal rings reduced force to 1 +/- 3%,
      significantly different from nifedipine alone (49 +/- 6%). Moreover, nonspecific
      NSCC inhibitors SKF-96365 and 2-aminoethyldiphenyl borate reduced force to 1 +/-
      1% and 19 +/- 7%, respectively. Intracellular Ca(2+) measurements in isolated ASM
      cells showed that KB-R7943 and SKF-96365 reduced the peak and sustained response
      to histamine (0.20 +/- 0.1 and 0.19 +/- 0.09 for KB-R, 0.43 +/- 0.16 and 0.47 +/-
      0.18 for SKF, expressed as mean of differences). Moreover, Na(+)-free solution
      only inhibited the sustained response (0.54 +/- 0.25). These data support an
      important role for NSCC and NCX during histamine stimulation. We speculate that
      histamine induces Na(+) influx through NSCC that promotes the Ca(2+) entry mode
      of NCX and Ca(V)1.2 channel activation, thereby causing contraction.

PMID- 17449795
TI  - Diesel exhaust particles induce matrix metalloprotease-1 in human lung epithelial
      cells via a NADP(H) oxidase/NOX4 redox-dependent mechanism.
AB  - Chronic exposure to particulate air pollution is associated with lung function
      impairment. To determine the molecular mechanism(s) of this phenomenon, we
      investigated, in an alveolar human epithelial cell line (A549), whether diesel
      exhaust particles (DEPs), a main component of particulate air pollution,
      modulates the expression and activity of the matrix metalloprotease (MMP)-1, a
      collagenase involved in alveolar wall degradation. Interaction of DEPs with
      cigarette smoke, which also produces structural and functional lung alterations,
      was also investigated. A noncytotoxic concentration of DEPs induced an increase
      in MMP-1 mRNA and protein expression and activity in A549 cells without modifying
      the expression of the MMP inhibitors TIMP-1 and -2. This effect was not
      potentiated when cells were coexposed to noncytotoxic concentrations of cigarette
      smoke condensate. DEP-induced MMP-1 was associated with increased ERK 1/2
      phosphorylation and upregulation of expression and activity of the NADPH oxidase
      analog NOX4. Cell transfection with a NOX4 small interfering RNA prevented these
      phenomena, showing the critical role of a NOX4 ERK 1/2 pathway in DEP-induced MMP
      1 expression and activity. Similar results to those observed in A549 cells were
      obtained in another human lung epithelial cell line, NCI-H292. Furthermore,
      experiments in mice intratracheally instilled with DEPs confirmed the in vitro
      findings, showing the induction of NOX4 and MMP-1 protein expression in alveolar
      epithelial cells. We conclude that alveolar alterations secondary to MMP-1
      induction could explain lung function impairment associated with exposure to
      particulate pollution.

PMID- 17449796
TI  - Effects of pulmonary ischemia on lung morphology.
AB  - Pulmonary ischemia resulting from chronic pulmonary embolism leads to
      proliferation of the systemic circulation within and surrounding the lung.
      However, it is not clear how well alveolar tissue is sustained during the time of
      complete pulmonary ischemia. In the present study, we investigated how pulmonary
      ischemia after left pulmonary artery ligation (LPAL) would alter lung mechanical
      properties and morphology. In this established mouse model of lung angiogenesis
      after chronic LPAL (10), we evaluated lung function and structure before (3 days)
      and after (14 days) a functional systemic circulation to the left lung is
      established. Age-matched naive and sham-operated C57Bl/6 mice and mice undergoing
      chronic LPAL were studied. Left and right lung pressure-volume relationships were
      determined. Next, lungs were inflated in situ with warmed agarose (25-30 cmH(2)O)
      and fixed, and mean chord lengths (MCL) of histological sections were quantified.
      MCL of naive mice averaged 43.9 +/- 1.8 mum. No significant changes in MCL were
      observed at either time point after LPAL. Left lung volumes and specific
      compliances were significantly reduced 3 days after LPAL. However, by 14 days
      after LPAL, lung pressure-volume relationships were not different from controls.
      These results suggest that severe pulmonary ischemia causes changes in lung
      mechanics early after LPAL that are reversed by the time a new systemic
      vasculature is known to perfuse pulmonary capillaries. The LPAL model thus
      affords a unique opportunity to study lung functional responses to tissue
      ischemia and subsequent recovery.

PMID- 17449797
TI  - Estrogen receptor-alpha regulates pulmonary alveolar loss and regeneration in
      female mice: morphometric and gene expression studies.
AB  - Pulmonary alveoli, especially in females, are estrogen-responsive structures:
      ovariectomy in wild-type (WT) adult mice results in alveolar loss, and estradiol
      replacement induces alveolar regeneration. Furthermore, estrogen receptor (ER)
      alpha and ER-beta are required for the developmental formation of a full
      complement of alveoli in female mice. We now show ovariectomy resulted in
      alveolar loss in adult ER-beta(-/-) mice but not in adult ER-alpha(-/-) mice.
      Estradiol treatment of ovariectomized ER-beta(-/-) mice induced alveolar
      regeneration. In ovariectomized WT mice, estradiol treatment resulted, within 1
      h, in RNA-level gene expression supportive of processes needed to form an
      alveolar septum, e.g., cell replication, angiogenesis, extracellular matrix
      remodeling, and guided cell motion. Among these processes, protein expression
      supporting angiogenesis and cell replication was elevated 1 and 3 h,
      respectively, after estradiol treatment; similar findings were not present in
      either mutant. We conclude: 1) loss of signaling via ER-beta is not required for
      postovariectomy-induced alveolar loss or estradiol-induced regeneration; this
      indicates ER-alpha is key for estrogen-related alveolar loss and regeneration in
      adult female mice; 2) taken together with prior work showing that developmental
      formation of a full complement of alveoli requires ER-alpha and ER-beta, the
      present findings indicate the developmental and regenerative formation of alveoli
      are regulated differently, i.e., signaling for alveolar regeneration is not
      merely a recapitulation of signaling for developmental alveologenesis; and 3) the
      timing of estradiol-induced gene expression in lung supportive of processes
      required to form a septum differs between ovariectomized WT and ER-beta(-/-)
      mice.

PMID- 17449798
TI  - Congestive heart failure is a rare event in patients receiving imatinib therapy.
AB  - A recent preclinical study suggested that imatinib may be cardiotoxic in some
      patients. We reviewed all reported serious adverse events of cardiac adverse
      events occurring in patients on clinical trials involving imatinib. Among 1276
      patients enrolled, 22 (1.7%) were identified as having symptoms that could be
      attributed to systolic heart failure. The median age was 70 years (range, 49 to
      83 years). The median time from start of imatinib therapy was 162 days (range, 2
      2045 days). At the time these events were reported, 8 (0.6%) were considered
      possibly or probably related to imatinib. A total of 18 patients had previous
      medical conditions predisposing to cardiac failure: congestive heart failure
      (CHF; 6 [27%] patients), diabetes mellitus (6 [27%] patients), hypertension (10
      [45%] patients), coronary artery disease (CAD; 8 [36%] patients), arrhythmia (3
      [14%] patients), and cardiomyopathy (1 [5%] patient). Of the 22 patients, 11
      continued imatinib therapy with dose adjustments and management for the CHF
      symptoms without further complications. Imatinib therapy as a causal factor of
      CHF is uncommon, mainly seen in elderly patients with preexisting cardiac
      conditions. Patients with previous cardiac history should be monitored closely
      and treated aggressively with standard medical therapy, including diuretics, if
      they develop symptoms suggestive of heart failure.

PMID- 17449799
TI  - Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of
      extracellular ATP and immune suppression.
AB  - In the immune system, extracellular ATP functions as a "natural adjuvant" that
      exhibits multiple proinflammatory effects. It is released by damaged cells as an
      indicator of trauma and cell death but can be inactivated by CD39 (nucleoside
      triphosphate diphosphohydrolase-1 [NTPDase 1]), an ectoenzyme that degrades ATP
      to AMP. Here, we show that CD39 is expressed primarily by immune-suppressive
      Foxp3(+) regulatory T (Treg) cells. In mice, the enzyme is present on virtually
      all CD4(+)CD25(+) cells. CD39 expression is driven by the Treg-specific
      transcription factor Foxp3 and its catalytic activity is strongly enhanced by T
      cell receptor (TCR) ligation. Activated Treg cells are therefore able to abrogate
      ATP-related effects such as P2 receptor-mediated cell toxicity and ATP-driven
      maturation of dendritic cells. Also, human Treg cells express CD39. In contrast
      to mice, CD39 expression in man is restricted to a subset of Foxp3(+) regulatory
      effector/memory-like T (T(REM)) cells. Notably, patients with the
      remitting/relapsing form of multiple sclerosis (MS) have strikingly reduced
      numbers of CD39(+) Treg cells in the blood. Thus, in humans CD39 is a marker of a
      Treg subset likely involved in the control of the inflammatory autoimmune
      disease.

PMID- 17449800
TI  - IFNgamma differentially controls the development of idiopathic pneumonia syndrome
      and GVHD of the gastrointestinal tract.
AB  - Although proinflammatory cytokines are key mediators of tissue damage during
      graft-versus-host disease (GVHD), IFNgamma has previously been attributed with
      both protective and pathogenic effects. We have resolved this paradox by using
      wild-type (wt), IFNgamma(-/-), and IFNgammaR(-/-) mice as donors or recipients in
      well-described models of allogeneic stem cell transplantation (SCT). We show that
      donor-derived IFNgamma augments acute GVHD via direct effects on (1) the donor T
      cell to promote T helper 1 (Th1) differentiation and (2) the gastrointestinal
      (GI) tract to augment inflammatory cytokine generation. However, these
      detrimental effects are overwhelmed by a protective role of IFNgamma in
      preventing the development of idiopathic pneumonia syndrome (IPS). This is the
      result of direct effects on pulmonary parenchyma to prevent donor cell migration
      and expansion within the lung. Thus, IFNgamma is the key cytokine differentially
      controlling the development of IPS and gastrointestinal GVHD after allogeneic
      SCT.

PMID- 17449801
TI  - The interaction between leukocytosis and other risk factors for thrombosis in
      essential thrombocythemia.

PMID- 17449802
TI  - Myelofibrosis evolving during imatinib treatment of a chronic myeloproliferative
      disease with coexisting BCR-ABL translocation and JAK2V617F mutation.

PMID- 17449804
TI  - Why make a diagnosis?

PMID- 17449805
TI  - PIL5, a phytochrome-interacting bHLH protein, regulates gibberellin
      responsiveness by binding directly to the GAI and RGA promoters in Arabidopsis
      seeds.
AB  - Previous work showed that PHYTOCHROME-INTERACTING FACTOR3-LIKE5 (PIL5), a light
      labile basic helix-loop-helix protein, inhibits seed germination by repressing
      GIBBERELLIN 3beta-HYDROXYLASE1 (GA3ox1) and GA3ox2 and activating a gibberellic
      acid (GA) catabolic gene (GA2ox2). However, we show persistent light-dependent
      and PIL5-inhibited germination behavior in the absence of both de novo GA
      biosynthesis and deactivation by GA2ox2, suggesting that PIL5 regulates not only
      GA metabolism but also GA responsiveness. PIL5 increases the expression of two GA
      repressor (DELLA) genes, GA-INSENSITIVE (GAI) and REPRESSOR OF GA1-3 (RGA/RGA1),
      in darkness. The hypersensitivity of gai-t6 rga-28 to red light and the
      suppression of germination defects of a rga-28 PIL5 overexpression line show the
      significant role of this transcriptional regulation in seed germination. PIL5
      also increases abscisic acid (ABA) levels by activating ABA biosynthetic genes
      and repressing an ABA catabolic gene. PIL5 binds directly to GAI and RGA
      promoters but not to GA and ABA metabolic gene promoters. Together, our results
      show that light signals perceived by phytochromes cause a reduction in the PIL5
      protein level, which in turn regulates the transcription of two DELLA genes
      directly and that of GA and ABA metabolic genes indirectly.

PMID- 17449806
TI  - Formation of DEG5 and DEG8 complexes and their involvement in the degradation of
      photodamaged photosystem II reaction center D1 protein in Arabidopsis.
AB  - The widely distributed DEGP proteases play important roles in the degradation of
      damaged and misfolded proteins. Arabidopsis thaliana contains 16 DEGP-like
      proteases, four of which are located in the chloroplast. Here, we show that DEG5
      and DEG8 form a hexamer in the thylakoid lumen and that recombinant DEG8 is
      proteolytically active toward both a model substrate (beta-casein) and
      photodamaged D1 protein of photosystem II (PSII), producing 16-kD N-terminal and
      18-kD C-terminal fragments. Inactivation of DEG5 and DEG8 resulted in increased
      sensitivity to photoinhibition. Turnover of newly synthesized D1 protein in the
      deg5 deg8 double mutant was impaired, and the degradation of D1 in the presence
      of the chloroplast protein synthesis inhibitor lincomycin under high-light
      treatment was slowed in the mutants. Thus, DEG5 and DEG8 are important for
      efficient turnover of the D1 protein and for protection against photoinhibition
      in vivo. The deg5 deg8 double mutant showed increased photosensitivity and
      reduced rates of D1 degradation compared with single mutants of deg5 and deg8. A
      16-kD N-terminal degradation fragment of the D1 protein was detected in wild-type
      plants but not in the deg5 deg8 mutant following in vivo photoinhibition.
      Therefore, our results suggest that DEG5 and DEG8 have a synergistic function in
      the primary cleavage of the CD loop of the PSII reaction center protein D1.

PMID- 17449807
TI  - An ERF transcription factor in Medicago truncatula that is essential for Nod
      factor signal transduction.
AB  - Rhizobial bacteria activate the formation of nodules on the appropriate host
      legume plant, and this requires the bacterial signaling molecule Nod factor.
      Perception of Nod factor in the plant leads to the activation of a number of
      rhizobial-induced genes. Putative transcriptional regulators in the GRAS family
      are known to function in Nod factor signaling, but these proteins have not been
      shown to be capable of direct DNA binding. Here, we identify an ERF transcription
      factor, ERF Required for Nodulation (ERN), which contains a highly conserved AP2
      DNA binding domain, that is necessary for nodulation. Mutations in this gene
      block the initiation and development of rhizobial invasion structures, termed
      infection threads, and thus block nodule invasion by the bacteria. We show that
      ERN is necessary for Nod factor-induced gene expression and for spontaneous
      nodulation activated by the calcium- and calmodulin-dependent protein kinase,
      DMI3, which is a component of the Nod factor signaling pathway. We propose that
      ERN is a component of the Nod factor signal transduction pathway and functions
      downstream of DMI3 to activate nodulation gene expression.

PMID- 17449808
TI  - The transcription factor WIN1/SHN1 regulates Cutin biosynthesis in Arabidopsis
      thaliana.
AB  - The composition and permeability of the cuticle has a large influence on its
      ability to protect the plant against various forms of biotic and abiotic stress.
      WAX INDUCER1 (WIN1) and related transcription factors have recently been shown to
      trigger wax production, enhance drought tolerance, and modulate cuticular
      permeability when overexpressed in Arabidopsis thaliana. We found that WIN1
      influences the composition of cutin, a polyester that forms the backbone of the
      cuticle. WIN1 overexpression induces compositional changes and an overall
      increase in cutin production in vegetative and reproductive organs, while its
      downregulation has the opposite effect. Changes in cutin composition are preceded
      by the rapid and coordinated induction of several genes known or likely to be
      involved in cutin biosynthesis. This transcriptional response is followed after a
      delay by the induction of genes associated with wax biosynthesis, suggesting that
      the regulation of cutin and wax production by WIN1 is a two-step process. We
      demonstrate that at least one of the cutin pathway genes, which encodes long
      chain acyl-CoA synthetase LACS2, is likely to be directly targeted by WIN1.
      Overall, our results suggest that WIN1 modulates cuticle permeability in
      Arabidopsis by regulating genes encoding cutin pathway enzymes.

PMID- 17449809
TI  - The Arabidopsis D-type cyclin CYCD4 controls cell division in the stomatal
      lineage of the hypocotyl epidermis.
AB  - Cyclin D (CYCD) plays an important role in cell cycle progression and reentry in
      response to external signals. Here, we demonstrate that Arabidopsis thaliana
      CYCD4 is associated with specific cell divisions in the hypocotyl. We observed
      that cycd4 T-DNA insertion mutants had a reduced number of nonprotruding cells
      and stomata in the hypocotyl epidermis. Conversely, CYCD4 overexpression enhanced
      cell division in nonprotruding cell files in the upper region of the hypocotyls,
      where stomata are usually formed in wild-type plants. The overproliferative cells
      were of stomatal lineage, which is marked by the expression of the TOO MANY
      MOUTHS gene, but unlike the meristemoids, most of them were not triangular.
      Although the phytohormone gibberellin promoted stomatal differentiation in the
      hypocotyl, inhibition of gibberellin biosynthesis did not prevent CYCD4 from
      inducing cell division. These results suggested that CYCD4 has a specialized
      function in the proliferation of stomatal lineage progenitors rather than in
      stomatal differentiation. We propose that CYCD4 controls cell division in the
      initial step of stomata formation in the hypocotyl.

PMID- 17449810
TI  - MONODEHYROASCORBATE REDUCTASE4 is required for seed storage oil hydrolysis and
      postgerminative growth in Arabidopsis.
AB  - Hydrogen peroxide is a major by-product of peroxisomal metabolism and has the
      potential to cause critical oxidative damage. In all eukaryotes, catalase is
      thought to be instrumental in removing this H(2)O(2). However, plants also
      contain a peroxisomal membrane-associated ascorbate-dependent electron transfer
      system, using ascorbate peroxidase and monodehydroascorbate reductase (MDAR).
      Here, I report that the conditional seedling-lethal sugar-dependent2 mutant of
      Arabidopsis thaliana is deficient in the peroxisomal membrane isoform of MDAR
      (MDAR4). Following germination, Arabidopsis seeds rely on storage oil breakdown
      to supply carbon skeletons and energy for early seedling growth, and massive
      amounts of H(2)O(2) are generated within the peroxisome as a by-product of fatty
      acid beta-oxidation. My data suggest that the membrane-bound MDAR4 component of
      the ascorbate-dependent electron transfer system is necessary to detoxify
      H(2)O(2), which escapes the peroxisome. This function appears to be critical to
      protect oil bodies that are in close proximity to peroxisomes from incurring
      oxidative damage, which otherwise inactivates the triacylglycerol lipase SUGAR
      DEPENDENT1 and cuts off the supply of carbon for seedling establishment.

PMID- 17449811
TI  - SCABP8/CBL10, a putative calcium sensor, interacts with the protein kinase SOS2
      to protect Arabidopsis shoots from salt stress.
AB  - The SOS (for Salt Overly Sensitive) pathway plays essential roles in conferring
      salt tolerance in Arabidopsis thaliana. Under salt stress, the calcium sensor
      SOS3 activates the kinase SOS2 that positively regulates SOS1, a plasma membrane
      sodium/proton antiporter. We show that SOS3 acts primarily in roots under salt
      stress. By contrast, the SOS3 homolog SOS3-LIKE CALCIUM BINDING PROTEIN8
      (SCABP8)/CALCINEURIN B-LIKE10 functions mainly in the shoot response to salt
      toxicity. While root growth is reduced in sos3 mutants in the presence of NaCl,
      the salt sensitivity of scabp8 is more prominent in shoot tissues. SCABP8 is
      further shown to bind calcium, interact with SOS2 both in vitro and in vivo,
      recruit SOS2 to the plasma membrane, enhance SOS2 activity in a calcium-dependent
      manner, and activate SOS1 in yeast. In addition, sos3 scabp8 and sos2 scabp8
      display a phenotype similar to sos2, which is more sensitive to salt than either
      sos3 or scabp8 alone. Overexpression of SCABP8 in sos3 partially rescues the sos3
      salt-sensitive phenotype. However, overexpression of SOS3 fails to complement
      scabp8. These results suggest that SCABP8 and SOS3 are only partially redundant
      in their function, and each plays additional and unique roles in the plant salt
      stress response.

PMID- 17449813
TI  - Guest editors' introduction.

PMID- 17449815
TI  - Constructing the landscape of the mammalian transcriptome.
AB  - The principal route to understanding the biological significance of the genome
      sequence comes from discovery and characterization of that portion of the genome
      that is transcribed into RNA products. We now know that this ;transcriptome' is
      unexpectedly complex and its precise definition in any one species requires
      multiple technical approaches and an ability to work on a very large scale. A key
      step is the development of technologies able to capture snapshots of the
      complexity of the various kinds of RNA generated by the genome. As the human,
      mouse and other model genome sequencing projects approach completion,
      considerable effort has been focused on identifying and annotating the protein
      coding genes as the principal output of the genome. In pursuing this aim, several
      key technologies have been developed to generate large numbers and highly diverse
      sets of full-length cDNAs and their variants. However, the search has identified
      another hidden transcriptional universe comprising a wide variety of non-protein
      coding RNA transcripts. Despite initial scepticism, various experiments and
      complementary technologies have demonstrated that these RNAs are dynamically
      transcribed and a subset of them can act as sense-antisense RNAs, which influence
      the transcriptional output of the genome. Recent experimental evidence suggests
      that the list of non-protein coding RNAs is still largely incomplete and that
      transcription is substantially more complex even than currently thought.

PMID- 17449816
TI  - Extracting biology from high-dimensional biological data.
AB  - The promise of the genome project was that a complete sequence would provide us
      with information that would transform biology and medicine. But the 'parts list'
      that has emerged from the genome project is far from the 'wiring diagram' and
      'circuit logic' we need to understand the link between genotype, environment and
      phenotype. While genomic technologies such as DNA microarrays, proteomics and
      metabolomics have given us new tools and new sources of data to address these
      problems, a number of crucial elements remain to be addressed before we can begin
      to close the loop and develop a predictive quantitative biology that is the
      stated goal of so much of current biological research, including systems biology.
      Our approach to this problem has largely been one of integration, bringing
      together a vast wealth of information to better interpret the experimental data
      we are generating in genomic assays and creating publicly available databases and
      software tools to facilitate the work of others. Recently, we have used a similar
      approach to trying to understand the biological networks that underlie the
      phenotypic responses we observe and starting us on the road to developing a
      predictive biology.

PMID- 17449817
TI  - Advanced sequencing technologies and their wider impact in microbiology.
AB  - In the past 10 years, microbiology has undergone a revolution that has been
      driven by access to cheap high-throughput DNA sequencing. It was not long ago
      that the cloning and sequencing of a target gene could take months or years,
      whereas now this entire process has been replaced by a 10 min Internet search of
      a public genome database. There has been no single innovation that has initiated
      this rapid technological change; in fact, the core chemistry of DNA sequencing is
      the same as it was 30 years ago. Instead, progress has been driven by large
      sequencing centers that have incrementally industrialized the Sanger sequencing
      method. A side effect of this industrialization is that large-scale sequencing
      has moved out of small research labs, and the vast majority of sequence data is
      now generated by large genome centers. Recently, there have been advances in
      technology that will enable high-throughput genome sequencing to be established
      in research labs using bench-top instrumentation. These new technologies are
      already being used to explore the vast microbial diversity in the natural
      environment and the untapped genetic variation that can occur in bacterial
      species. It is expected that these powerful new methods will open up new
      questions to genomic investigation and will also allow high-throughput sequencing
      to be more than just a discovery exercise but also a routine assay for hypothesis
      testing. While this review will concentrate on microorganisms, many of the
      important arguments about the need to measure and understand variation at the
      species, population and ecosystem level will hold true for many other biological
      systems.

PMID- 17449818
TI  - A new paradigm for developmental biology.
AB  - It is usually thought that the development of complex organisms is controlled by
      protein regulatory factors and morphogenetic signals exchanged between cells and
      differentiating tissues during ontogeny. However, it is now evident that the
      majority of all animal genomes is transcribed, apparently in a developmentally
      regulated manner, suggesting that these genomes largely encode RNA machines and
      that there may be a vast hidden layer of RNA regulatory transactions in the
      background. I propose that the epigenetic trajectories of differentiation and
      development are primarily programmed by feed-forward RNA regulatory networks and
      that most of the information required for multicellular development is embedded
      in these networks, with cell-cell signalling required to provide important
      positional information and to correct stochastic errors in the endogenous RNA
      directed program.

PMID- 17449819
TI  - Biological impacts and context of network theory.
AB  - Many complex systems can be represented and analyzed as networks, and examples
      that have benefited from this approach span the natural sciences. For instance,
      we now know that systems as disparate as the World Wide Web, the Internet,
      scientific collaborations, food webs, protein interactions and metabolism all
      have common features in their organization, the most salient of which are their
      scale-free connectivity distributions and their small-world behavior. The recent
      availability of large-scale datasets that span the proteome or metabolome of an
      organism have made it possible to elucidate some of the organizational principles
      and rules that govern their function, robustness and evolution. We expect that
      combining the currently separate layers of information from gene regulatory
      networks, signal transduction networks, protein interaction networks and
      metabolic networks will dramatically enhance our understanding of cellular
      function and dynamics.

PMID- 17449820
TI  - Modelling genotype-phenotype relationships and human disease with genetic
      interaction networks.
AB  - Probably all heritable traits, including disease susceptibility, are affected by
      interactions between mutations in multiple genes. We understand little, however,
      about how genes interact to produce phenotypes, and there is little power to
      detect interactions between genes in human population studies. An alternative
      approach towards understanding how mutations combine to produce phenotypes is to
      construct systematic genetic interaction networks in model organisms. Here I
      describe the methods that are being used to map genetic interactions in yeast and
      C. elegans, and the insights that these networks provide for human disease. I
      also discuss the mechanistic interpretation of genetic interaction networks, how
      genetic interactions can be used to understand gene function, and methods that
      have been developed to predict genetic interactions on a genome-wide scale.

PMID- 17449821
TI  - Variable gene expression in eukaryotes: a network perspective.
AB  - Changes in gene expression underlie phenotypic plasticity, variation within
      species, and phenotypic divergence between species. These expression differences
      arise from modulation of regulatory networks. To understand the source of
      expression differences, networks of interactions among genes and gene products
      that orchestrate gene expression must be considered. Here I review the basic
      structure of eukaryotic regulatory networks and discuss selected case studies
      that provide insight into how these networks are altered to create expression
      differences within and between species.

PMID- 17449822
TI  - Computational biology of cardiac myocytes: proposed standards for the physiome.
AB  - Predicting information about human physiology and pathophysiology from genomic
      data is a compelling, but unfulfilled goal of post-genomic biology. This is the
      aim of the so-called Physiome Project and is, undeniably, an ambitious goal. Yet
      if we can exploit even a small proportion of the rich and varied experimental
      data currently available, significant insights into clinically important aspects
      of human physiology will follow. To achieve this requires the integration of data
      from disparate sources into a common framework. Extrapolation of available data
      across species, laboratory techniques and conditions requires a quantitative
      approach. Mathematical models allow us to integrate molecular information into
      cellular, tissue and organ-level, and ultimately clinically relevant scales. In
      this paper we argue that biophysically detailed computational modelling provides
      the essential tool for this process and, furthermore, that an appropriate
      framework for annotating, databasing and critiquing these models will be
      essential for the development of integrative computational biology.

PMID- 17449823
TI  - Interpreting physiological responses to environmental change through gene
      expression profiling.
AB  - Identification of differentially expressed genes in response to environmental
      change offers insights into the roles of the transcriptome in the regulation of
      physiological responses. A variety of methods are now available to implement
      large-scale gene expression screens, and each method has specific advantages and
      disadvantages. Construction of custom cDNA microarrays remains the most popular
      route to implement expression screens in the non-model organisms favored by
      comparative physiologists, and we highlight some factors that should be
      considered when embarking along this path. Using a carp cDNA microarray, we have
      undertaken a broad, system-wide gene expression screen to investigate the
      physiological mechanisms underlying cold and hypoxia acclimation. This dataset
      provides a starting point from which to explore a range of specific mechanistic
      hypotheses at all levels of organization, from individual biochemical pathways to
      the level of the whole organism. We demonstrate the utility of two data analysis
      methods, Gene Ontology profiling and rank-based statistical methods, to summarize
      the probable physiological function of acclimation-induced gene expression
      changes, and to prioritize specific genes as candidates for further study.

PMID- 17449824
TI  - Functional genomics and proteomics of the cellular osmotic stress response in
      'non-model' organisms.
AB  - All organisms are adapted to well-defined extracellular salinity ranges.
      Osmoregulatory mechanisms spanning all levels of biological organization, from
      molecules to behavior, are central to salinity adaptation. Functional genomics
      and proteomics approaches represent powerful tools for gaining insight into the
      molecular basis of salinity adaptation and euryhalinity in animals. In this
      review, we discuss our experience in applying such tools to so-called 'non-model'
      species, including euryhaline animals that are well-suited for studies of
      salinity adaptation. Suppression subtractive hybridization, RACE-PCR and mass
      spectrometry-driven proteomics can be used to identify genes and proteins
      involved in salinity adaptation or other environmental stress responses in
      tilapia, sharks and sponges. For protein identification in non-model species,
      algorithms based on sequence homology searches such as MSBLASTP2 are most
      powerful. Subsequent gene ontology and pathway analysis can then utilize sets of
      identified genes and proteins for modeling molecular mechanisms of environmental
      adaptation. Current limitations for proteomics in non-model species can be
      overcome by improving sequence coverage, N- and C-terminal sequencing and
      analysis of intact proteins. Dependence on information about biochemical pathways
      and gene ontology databases for model species represents a more severe barrier
      for work with non-model species. To minimize such dependence, focusing on a
      single biological process (rather than attempting to describe the system as a
      whole) is key when applying 'omics' approaches to non-model organisms.

PMID- 17449825
TI  - Comparative environmental genomics in non-model species: using heterologous
      hybridization to DNA-based microarrays.
AB  - The emerging field of comparative environmental genomics involves the cross
      species comparison of broad-scale patterns of gene expression. Often, the goal is
      to elucidate the evolutionary basis or ecological implications of genomic
      responses to environmental stimuli. DNA-based microarrays represent powerful
      means with which to investigate gene expression, and the application of genomic
      tools to studies on non-model species is becoming increasingly feasible. The use
      of a microarray generated from one species to probe gene expression in another, a
      method termed 'heterologous hybridization', eliminates the need to fabricate
      novel microarray platforms for every new species of interest. In this review,
      recent advances in heterologous hybridization are reviewed, and the technical
      caveats of this approach are discussed.

PMID- 17449826
TI  - Common aging pathways in worms, flies, mice and humans.
AB  - Development of functional genomics tools has made it possible to define the aging
      process by performing genome-wide scans for transcriptional differences between
      the young and the old. Global screens for age regulation have been performed for
      worms and flies, as well as many tissues in mice and humans. Recent work has
      begun to analyze the similarities and differences in transcriptional changes in
      aging among different species. Most age-related expression changes are specific
      for a given species, but genes in one pathway (the electron transport chain
      pathway) show common age regulation in species from worms to humans. Evolutionary
      theories of aging provide a basis to understand how age regulation of a genetic
      pathway might be preserved between distantly related species.

PMID- 17449827
TI  - The biological importance of measuring individual variation.
AB  - Functional genomics research using Fundulus heteroclitus has focused on variation
      among individuals because of the evolutionary importance and value of Fundulus in
      explaining the human condition (why individual humans are different and are
      affected differently by stress, disease and drugs). Among different populations
      and species of Fundulus, there are evolutionarily adaptive differences in gene
      expression. This natural variation in gene expression seems to affect cardiac
      metabolism because up to 81% of the variation in glucose utilization observed in
      isolated heart ventricles is related to specific patterns of gene expression. The
      surprising result from this research is that among different groups of
      individuals, the expression of mRNA from different metabolic pathways explains
      substrate-specific metabolism. For example, variation in oxidative
      phosphorylation mRNAs explains glucose metabolism for one group of individuals
      but expression of glucose metabolism genes explains this metabolism in a
      different group of individuals. This variation among individuals has important
      implications for studies using inbred strains: conclusions based on one
      individual or one strain will not necessarily reflect a generalized conclusion
      for a population or species. Finally, there are surprisingly strong positive and
      negative correlations among metabolic genes, both within and between pathways.
      These data suggest that measures of mRNA expression are meaningful, yet there is
      a complexity in how gene expression is related to physiological processes.

PMID- 17449828
TI  - Revisiting the Krogh Principle in the post-genome era: Caenorhabditis elegans as
      a model system for integrative physiology research.
AB  - Molecular biology drove a powerful reductionist or ;molecule-centric' approach to
      biological research in the last half of the 20th century. Reductionism is the
      attempt to explain complex phenomena by defining the functional properties of the
      individual components that comprise multi-component systems. Systems biology has
      emerged in the post-genome era as the successor to reductionism. In my opinion,
      systems biology and physiology are synonymous. Both disciplines seek to
      understand multi-component processes or 'systems' and the underlying pathways of
      information flow from an organism's genes up through increasingly complex levels
      of organization. The physiologist and Nobel laureate August Krogh believed that
      there is an ideal organism in which almost every physiological problem could be
      studied most readily (the 'Krogh Principle'). If an investigator's goal were to
      define a physiological process from the level of genes to the whole animal, the
      optimal model organism for him/her to utilize would be one that is genetically
      and molecularly tractable. In other words, an organism in which forward and
      reverse genetic analyses could be carried out readily, rapidly and economically.
      Non-mammalian model organisms such as Escherichia coli, Saccharomyces,
      Caenorhabditis elegans, Drosophila, zebrafish and the plant Arabidopsis are
      cornerstones of systems biology research. The nematode C. elegans provides a
      particularly striking example of the experimental utility of non-mammalian model
      organisms. The aim of this paper is to illustrate how genetic, functional
      genomic, molecular and physiological methods can be combined in C. elegans to
      develop a systems biological understanding of fundamental physiological processes
      common to all animals. I present examples of the experimental tools available for
      the study of C. elegans and discuss how we have used them to gain new insights
      into osmotic stress signaling in animal cells.

PMID- 17449829
TI  - Integrative physiology, functional genomics and the phenotype gap: a guide for
      comparative physiologists.
AB  - Classical, curiosity-led comparative physiology finds itself at a crossroads.
      Major funding for classical physiology is becoming harder to find, as grant
      agencies focus on more molecular approaches or on science with more immediate
      strategic value to their respective countries. In turn, this shift in funding
      places Zoology and Animal Science departments under enormous stress: student
      numbers are buoyant, but how can research funding be maintained at high levels?
      Our research group has argued for the redefinition of integrative physiology as
      the investigation of gene function in an organotypic context in the intact
      animal. Implicit in this definition is the use of transgenics and reverse
      genetics to manipulate gene function in a cell-specific manner; this in turn
      implies the use of a genetically tractable 'model organism'. The significance of
      this definition is that it aligns integrative physiology with functional
      genomics. Again, functional genomics draws heavily on reverse genetics to
      elucidate the function of novel genes. The phenotype gap (the mismatch between
      what a genetic model organism's genome encodes and the reasons that it has
      historically been studied) emphasises the need to attract and empower functional
      biologists: can all 13,500 genes in Drosophila really be explained in terms of
      developmental biology? So, by embracing the integrative physiology manifesto,
      comparative physiologists can not only accelerate their own research, but their
      functional skills can make them indispensable in the post-genomic endeavour.

PMID- 17449830
TI  - Historical reconstructions of evolving physiological complexity: O2 secretion in
      the eye and swimbladder of fishes.
AB  - The ability of some fishes to inflate their compressible swimbladder with almost
      pure oxygen to maintain neutral buoyancy, even against the high hydrostatic
      pressure several thousand metres below the water surface, has fascinated
      physiologists for more than 200 years. This review shows how evolutionary
      reconstruction of the components of such a complex physiological system on a
      phylogenetic tree can generate new and important insights into the origin of
      complex phenotypes that are difficult to obtain with a purely mechanistic
      approach alone. Thus, it is shown that oxygen secretion first evolved in the eyes
      of fishes, presumably for improved oxygen supply to an avascular, metabolically
      active retina. Evolution of this system was facilitated by prior changes in the
      pH dependence of oxygen-binding characteristics of haemoglobin (the Root effect)
      and in the specific buffer value of haemoglobin. These changes predisposed
      teleost fishes for the later evolution of swimbladder oxygen secretion, which
      occurred at least four times independently and can be associated with increased
      auditory sensitivity and invasion of the deep sea in some groups. It is proposed
      that the increasing availability of molecular phylogenetic trees for evolutionary
      reconstructions may be as important for understanding physiological diversity in
      the postgenomic era as the increase of genomic sequence information in single
      model species.

PMID- 17449831
TI  - Evolvability of physiological and biochemical traits: evolutionary mechanisms
      including and beyond single-nucleotide mutation.
AB  - A longstanding challenge for biologists has been to explain not just how
      organisms are adapted to diverse environments, but how these adaptations arise.
      Although natural selection is clearly sufficient to act on heritable variation,
      is this heritable variation sufficient to yield complex adaptations and how does
      this variation itself arise? Much prior focus has been on mutation of single
      nucleotides in genes. This process is common and can have dramatic phenotypes,
      but could be limited in its ability to culminate in complex adaptations for two
      kinds of reasons: (i) because natural selection is powerful, it can purge genetic
      variation, and (ii) evolutionary transition from the absence to the presence of a
      complex adaptation seemingly requires multiple mutations at the right place and
      time and in the right sequence, with each intermediate stage having increased
      overall fitness; this seems highly improbable. Because the networks that
      organisms comprise are hierarchical and redundant and have modular structure,
      however, single-nucleotide mutations can have large and tolerable impacts.
      Diverse mechanisms, collectively evolutionary capacitors, can shield genetic
      variation from the purgative of selection. These features can enable evolution to
      proceed via single-nucleotide mutation. Importantly, single-nucleotide mutation
      usually only modifies existing genes rather than creating new ones, and numerous
      other mechanisms eclipse single-nucleotide mutation in creating genetic
      variation. These include gene duplication (both segmental and whole-genome),
      lateral gene transfer, hybridization, mobile genetic elements and symbiosis.
      Other processes can scramble and reassemble nucleotide sequence. The mechanisms
      beyond single-gene mutation offer considerable promise in detailing the evolution
      of complex physiological and biochemical traits, and have already done so for
      several morphological traits.

PMID- 17449832
TI  - Trends in medication treatment for ADHD.
AB  - OBJECTIVE: This study examines demographic trends in the use of medications to
      treat ADHD in adult and pediatric populations. METHOD: Using pharmacy claims data
      for a large population of commercially insured Americans, the study measures ADHD
      treatment prevalence and drug use from 2000 to 2005. RESULTS: In 2005, 4.4% of
      children (ages 0 to 19) and 0.8% of adults (ages 20 and older) used ADHD
      medications. Treatment rates were higher in boys (6.1%) than in girls (2.6%), but
      the rates for men and women were approximately equal (0.8%). During the period of
      the study, treatment prevalence increased rapidly (11.8% per year) for the
      population as a whole. Treatment rates grew more rapidly for adults than for
      children, more rapidly for women than for men, and more rapidly for girls than
      for boys. CONCLUSION: Improved identification of ADHD in adult and female
      patients has contributed to rapid growth in ADHD medication use.

PMID- 17449833
TI  - Lower extremity response time performance in boys with ADHD.
AB  - OBJECTIVE: Children with ADHD have been labeled as "uncoordinated" and
      "inefficient movers"; however, a paucity of research has systematically examined
      "stimulant-free" motor processing in this population. METHOD: In the present
      investigation, the authors employ a cross-lateral integration task to assess the
      attainment of a motor milestone in a corpus of 16 adolescents with ADHD acutely
      removed from their daily medication routine (methylphenidate) and 19 age-matched
      peers. Participants perform a choice response time task involving the lower
      extremity to targets located at midline and in ipsilateral and contralateral
      space. RESULTS/CONCLUSION: This investigation finds that children with ADHD have
      slower lower extremity reaction and movement times compared to controls, and all
      preadolescent children demonstrate an inhibition in processing movements that
      require crossing the midline of the body.

PMID- 17449835
TI  - Behavior and peer status in children with ADHD: continuity and change.
AB  - OBJECTIVE: Children with ADHD experience peer problems that may place them at
      risk for adverse outcomes. Using a short-term longitudinal design, this study
      links specific behaviors to peer functioning in groups of previously unfamiliar
      children with ADHD. METHOD: The participants were 268 children with ADHD who took
      part in an intensive summer treatment program. The program used a comprehensive
      behavioral point system that yielded observational data for 12 behavioral
      categories. These behavioral categories were used to predict peer acceptance,
      rejection, and liking assessed at three times during the program. RESULTS:
      Following activity rules, helping, whining, and attention emerged as best
      predictors of initial peer status. Subsequent helping behaviors and activity rule
      following predicted changes in peer status, but their contributions were small.
      CONCLUSION: The results indicate that increasing helping and rule- following
      behaviors may improve peer functioning of children with ADHD in similar settings.

PMID- 17449834
TI  - Self-regulation of visual attention and facial expression of emotions in ADHD
      children.
AB  - OBJECTIVE: To test if visual focusing and mimic display as features of self
      regulation in ADHD children show a curvilinear relation to rising methylphenidate
      (MPH) doses. To test if small dose steps of 2.5mg MPH cause significant changes
      in behavior. And to test the relation of these features to intellectual
      performance, parents' ratings, and clinical outcome. METHOD: Twenty-five children
      of a clinical convenience sample are filmed playing cards and doing oral
      arithmetic exercises without medication and after intake of MPH raised in steps
      of 2.5 mg. Recordings are revised by four blinded raters counting visual focus
      loss and rating the variability of patients' smile. RESULTS: All hypotheses are
      confirmed. Best self-regulation coincides with best intellectual performance,
      highly significant improvement in parents' ratings, and good clinical outcome.
      CONCLUSION: The procedure could be helpful for MPH dose finding in the
      physician's practice and make therapy more efficient by means of a more precise
      dosage.

PMID- 17449836
TI  - Task demands interact with the single and combined effects of medication and
      contingencies on children with ADHD.
AB  - OBJECTIVE: To investigate single and combined effects of stimulant medication and
      contingencies on the performance of ADHD children with tasks involving different
      cognitive demands. METHOD: Children diagnosed with ADHD participated in a within
      subjects design. At two separate sessions, children on either medication or
      placebo (administered in a double-blind fashion) completed two tasks, a match-to
      sample task and a stop-signal task, under three conditions (reward, response
      cost, and no contingency) in a counterbalanced order. RESULTS: Contingencies and
      medication administered singly improved performance on both tasks. For the match
      to-sample task, the combination of medication and contingencies was more
      efficacious than either alone. For the stop-signal task, the combination of
      medication and reward was no more effective than either alone; however,
      medication and response cost combined was more effective than either treatment
      alone. CONCLUSION: Results suggest that both medication and contingencies improve
      task performance. The findings suggest that task demands interact with single and
      combined treatment effects.

PMID- 17449837
TI  - The Clinical Utility of the Behavior Rating Inventory of Executive Function
      (BRIEF) in the diagnosis of ADHD.
AB  - OBJECTIVE: Current theories hypothesize that deficits in executive functioning
      (EF) are responsible for the symptoms of ADHD and that specific patterns of EF
      deficits may be associated with different subtypes of ADHD. The present study
      evaluates the validity and clinical usefulness of the Behavior Rating Inventory
      of Executive Function, a behavior rating scale designed to assess dimensions of
      EF. METHOD: Participants include 70 boys and girls between the ages of 5 and 13
      referred to a university-based clinic for assessment of ADHD. RESULTS: Results
      indicate low interrater reliability but acceptable convergent validity.
      CONCLUSION: Parent report on the Behavior Regulation scale differentiates the
      ADHD-Combined Type group from the ADHD-Inattentive Type and non-ADHD groups, and
      the Metacognitive Index differentiates both ADHD subtypes from the non-ADHD
      group, thus supporting the clinical utility of this measure in a clinic-referred
      sample.

PMID- 17449839
TI  - Effects of auditory distraction on cognitive processing of young adults.
AB  - OBJECTIVE: The effects of interference, competition, and distraction on cognitive
      processing are unclearly understood, particularly regarding type and intensity of
      auditory distraction across a variety of cognitive processing tasks. METHOD: The
      purpose of this investigation was to report two experiments that sought to
      explore the effects of types of distraction (4-talker babble; word repetition;
      combined 4-talker babble with word repetition) when compared to a control
      condition of quiet on a range of computerized measures (simple reaction time;
      choice reaction time; serial pattern matching; lexical decision-making; visual
      selective attention; response reversal and rapid visual scanning; and form
      discrimination) in 40 young adults (Experiment 1). RESULTS: Few distraction
      effects were found on cognitive processing at the comfortable loudness level
      (40dB SL). In Experiment 2, statistically significant differences for choice
      reaction time and serial pattern matching (working memory) were found in both
      speed and accuracy when distractions were presented at perceived uncomfortable
      loudness levels (ULL) and compared with conditions of quiet and comfortable
      loudness level (40dB SL). CONCLUSION: Cognitive resource allocation models may be
      useful in interpreting the effects of auditory distraction on cognitive
      linguistic processing, and this model may help to explain differential
      distraction effects in clinical populations with attention deficits.

PMID- 17449838
TI  - Perceptions of academic skills of children diagnosed with ADHD.
AB  - OBJECTIVE: This study investigates how the academic skills of children diagnosed
      with ADHD are perceived by teachers, parents, and the children themselves.
      METHOD: The authors analyze data collected for third graders in spring 2002 in
      the nationally representative Early Childhood Longitudinal Survey. They use
      linear regressions to estimate independent associations between perceptions of
      academic abilities and parent-reported ADHD diagnoses, controlling for scores on
      standardized reading and math tests, assessments of externalizing behaviors, and
      other factors. RESULTS: Results show that for ADHD-diagnosed girls compared to
      other girls, both parents' and teachers' perceptions are substantially more
      negative. For ADHD-diagnosed boys, the differentials are also negative but less
      pronounced. Self-perceptions are not significantly different by ADHD status,
      except for boys' more negative self-perceptions related to math. CONCLUSION:
      Given the potentially damaging effects of these negative perceptions and
      expectations on self-esteem, motivation, and performance, efforts may be needed
      to bring perceptions of ADHD children more in line with the abilities they
      demonstrate on objective assessments. (J. of Att. Dis. 2007; 10(4) 390-397).

PMID- 17449840
TI  - Informativeness of maternal reports on the diagnosis of ADHD: an analysis of
      mother and youth reports.
AB  - OBJECTIVE: We evaluated correlates of the diagnosis of ADHD in youth by informant
      source. METHOD: Ninety-four pairs of mother reports and youth self-reports on
      ADHD were independently assessed, using diagnostic interviews from a large study
      of youth of both genders with and without ADHD. Comparisons were made on measures
      of interpersonal, school, and family functioning; treatment history; and parental
      psychopathology by informant source. RESULTS: With the exception of higher rates
      of ADHD-associated impairment and higher frequency of treatment for ADHD in the
      combined youth-mother group. There were no other differences in any other
      clinical or familial correlates by informant source; both informant groups had
      higher levels of impairment in multiple nonoverlapping measures of dysfunction
      than controls. Males were overrepresented among the mother-only group.
      CONCLUSION: Maternal reports of ADHD result in a meaningful diagnosis of ADHD
      with high levels of impairment, regardless of endorsement by the affected youth.

PMID- 17449842
TI  - Clinical commentary: the case of Sally.

PMID- 17449848
TI  - Identification of secretory granule phosphatidylinositol 4,5-bisphosphate
      interacting proteins using an affinity pulldown strategy.
AB  - Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) synthesis is required for
      calcium-dependent exocytosis in neurosecretory cells. We developed a
      PtdIns(4,5)P2 bead pulldown strategy combined with subcellular fractionation to
      identify endogenous chromaffin granule proteins that interact with PtdIns(4,5)P2.
      We identified two synaptotagmin isoforms, synaptotagmins 1 and 7; spectrin; alpha
      adaptin; and synaptotagmin-like protein 4 (granuphilin) by mass spectrometry and
      Western blotting. The interaction between synaptotagmin 7 and PtdIns(4,5)P2 and
      its functional relevance was investigated. The 45-kDa isoform of synaptotagmin 7
      was found to be highly expressed in adrenal chromaffin cells compared with PC12
      cells and to mainly localize to secretory granules by subcellular fractionation,
      immunoisolation, and immunocytochemistry. We demonstrated that synaptotagmin 7
      binds PtdIns(4,5)P2 via the C2B domain in the absence of calcium and via both the
      C2A and C2B domains in the presence of calcium. We mutated the polylysine stretch
      in synaptotagmin 7 C2B and demonstrated that this mutant domain lacks the calcium
      independent PtdIns(4,5)P2 binding. Synaptotagmin 7 C2B domain inhibited
      catecholamine release from digitonin-permeabilized chromaffin cells, and this
      inhibition was abrogated with the C2B polylysine mutant. These data indicate that
      synaptotagmin 7 C2B-effector interactions, which occur via the polylysine
      stretch, including calcium-independent PtdIns(4,5)P2 binding, are important for
      chromaffin granule exocytosis.

PMID- 17449849
TI  - Banking for the future: investing in human milk.

PMID- 17449850
TI  - Neonatal transfers--a thin layer of glue to keep the service network together?

PMID- 17449851
TI  - Estimated fetal weights versus birth weights: should the reference intrauterine
      growth curves based on birth weights be retired?

PMID- 17449852
TI  - ILCOR and neonatal resuscitation 2005.

PMID- 17449853
TI  - Vesicoamniotic shunting for fetal lower urinary tract obstruction: an overview.

PMID- 17449854
TI  - Pneumopericardium in a term infant on nasal continuous positive airway pressure.

PMID- 17449855
TI  - An unusual complication of phototherapy.

PMID- 17449856
TI  - Postmortem magnetic resonance imaging as an adjunct to perinatal autopsy for
      renal-tract abnormalities.
AB  - The aim of this study was to compare postmortem magnetic resonance imaging (MRI)
      of the renal system with autopsy in perinatal and fetal deaths. 37 deaths were
      studied and renal abnormalities were found in five of these cases. Postmortem MRI
      provided information of diagnostic utility comparable to that obtained by
      autopsy.

PMID- 17449857
TI  - Should pulse oximetry be used to screen for congenital heart disease?
AB  - Ten studies (44 969 newborns, 71 severe defects) evaluating the usefulness of
      neonatal pulse oximetry (PO) screening in timely detection of congenital heart
      disease (CHD) were reviewed. PO showed a high specificity (99.9-99.99%), and the
      overall rate of detection of 15 individual defects with PO was 72% (range 46
      100%), exceeding that of the clinical examination 58% (9-86%). Similar results
      were obtained for cyanotic CHD (89% v 69%, respectively). Without PO, discharge
      of apparently healthy infants with unknown CHD was 5.5 times and 4.1 times more
      likely in cyanotic CHD and all serious CHD, respectively. The paper describes the
      technical and practical details of first day and later screening. Diagnosis is
      reached earliest with first day screening, but it requires more resources. PO
      screening is not sensitive enough to serve as an independent screen, but along
      with the clinical examination it helps minimise the morbidity and mortality
      associated with discharge without diagnosis. Further research is needed for
      precise delineation of populations that would benefit from PO screening.

PMID- 17449858
TI  - Dysmorphology demystified.

PMID- 17449859
TI  - Arvo Ylppo (1887-1992): pioneer of Finnish paediatrics.
AB  - Besides developing the clinical and social care of children throughout Finland
      from 1920 onwards, the earlier research of Ylppo in Germany had laid the
      foundations world wide for scientific progress in the understanding and care of
      the premature infant.

PMID- 17449860
TI  - Malposition of endotracheal tube: association with pneumothorax in ventilated
      neonates.

PMID- 17449861
TI  - Predictors of clinical outcome for infants transferred for extracorporeal life
      support consideration.

PMID- 17449862
TI  - Variations in practice among paediatric consultants when referring unexpected
      neonatal deaths to a coroner.

PMID- 17449863
TI  - Changes in molecular species profiles of glycosylphosphatidylinositol anchor
      precursors in early stages of biosynthesis.
AB  - Glycosylphosphatidylinositol (GPI) anchor is a major lipidation in
      posttranslational modification. GPI anchor precursors are biosynthesized from
      endogenous phosphatidylinositols (PIs) and attached to proteins in the
      endoplasmic reticulum. Endogenous PIs are characterized by domination of diacyl
      species and the presence of polyunsaturated fatty acyl chain, such as 18:0-20:4,
      at the sn-2 position. In contrast, the features of mammalian
      glycosylphosphatidylinositol-anchored proteins (GPI-APs) are domination of
      alkyl/acyl PI species and the presence of saturated fatty acyl chains at the sn-2
      position, the latter being consistent with association with lipid rafts. Recent
      studies showed that saturated fatty acyl chain at sn-2 is introduced by fatty
      acid remodeling that occurs in GPI-APs. To gain insight into the former feature,
      we analyzed the molecular species of several different GPI precursors derived
      from various mammalian mutant cell lines. Here, we show that the PI species
      profile greatly changed in the precursor glucosamine (GlcN)-acyl-PI and became
      very similar to that of GPI-APs before fatty acid remodeling. They had alkyl (or
      alkenyl)/acyl types with unsaturated acyl chain as the major PI species.
      Therefore, a specific feature of the PI moieties of mature GPI-APs, domination of
      alkyl (or alkenyl)/acyl type species over diacyl types, is established at the
      stage of GlcN-acyl-PI.

PMID- 17449864
TI  - Secreted PCSK9 downregulates low density lipoprotein receptor through receptor
      mediated endocytosis.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease that
      regulates low density lipoprotein receptor (LDLR) protein levels. The mechanisms
      of this action, however, remain to be defined. We show here that recombinant
      human PCSK9 expressed in HEK293 cells was readily secreted into the medium, with
      the prosegment associated with the C-terminal domain. Secreted PCSK9 mediated
      cell surface LDLR degradation in a concentration- and time-dependent manner when
      added to HEK293 cells. Accordingly, cellular LDL uptake was significantly reduced
      as well. When infused directly into C57B6 mice, purified human PCSK9
      substantially reduced hepatic LDLR protein levels and resulted in increased
      plasma LDL cholesterol. When added to culture medium, fluorescently labeled PCSK9
      was endocytosed and displayed endosomal-lysosomal intracellular localization in
      HepG2 cells, as was demonstrated by colocalization with DiI-LDL. PCSK9
      endocytosis was mediated by LDLR as LDLR deficiency (hepatocytes from LDLR null
      mice), or RNA interference-mediated knockdown of LDLR markedly reduced PCSK9
      endocytosis. In addition, RNA interference knockdown of the autosomal recessive
      hypercholesterolemia (ARH) gene product also significantly reduced PCSK9
      endocytosis. Biochemical analysis revealed that the LDLR extracellular domain
      interacted directly with secreted PCSK9; thus, overexpression of the LDLR
      extracellular domain was able to attenuate the reduction of cell surface LDLR
      levels by secreted PCSK9. Together, these results reveal that secreted PCSK9
      retains biological activity, is able to bind directly to the LDLR extracellular
      domain, and undergoes LDLR-ARH-mediated endocytosis, leading to accelerated
      intracellular degradation of the LDLR.

PMID- 17449866
TI  - Tending Neurospora: David Perkins, 1919-2007, and Dorothy Newmeyer Perkins, 1922
      2007.

PMID- 17449868
TI  - Good practice in statistical reporting for Family Practice.

PMID- 17449867
TI  - Interaction of Epe1 with the heterochromatin assembly pathway in
      Schizosaccharomyces pombe.
AB  - Epe1 is a JmjC domain protein that antagonizes heterochromatization in
      Schizosaccharomyces pombe. Related JmjC domain proteins catalyze a histone
      demethylation reaction that depends on Fe(II) and alpha-ketoglutarate. However,
      no detectable demethylase activity is associated with Epe1, and its JmjC domain
      lacks conservation of Fe(II)-binding residues. We report that Swi6 recruits Epe1
      to heterochromatin and that overexpression of epe1+, like mutations in silencing
      genes or overexpression of swi6+, upregulates expression of certain genes. A
      significant overlap was observed between the lists of genes that are upregulated
      by overexpression of epe1+ and those that are upregulated by mutations in histone
      deacetylase genes. However, most of the common genes are not regulated by Clr4
      histone methyltransferase. This suggests that Epe1 interacts with the
      heterochromatin assembly pathway at the stage of histone deacetylation.
      Mutational inactivation of Epe1 downregulates approximately 12% of S. pombe
      genes, and the list of these genes overlaps significantly with the lists of genes
      that are upregulated by mutations in silencing genes and genes that are
      hyperacetylated at their promoter regions in clr6-1 mutants. We propose that an
      interplay between the repressive HDACs activity and Epe1 helps to regulate gene
      expression in S. pombe.

PMID- 17449869
TI  - Identification of a novel prostaglandin reductase reveals the involvement of
      prostaglandin E2 catabolism in regulation of peroxisome proliferator-activated
      receptor gamma activation.
AB  - This report identifies a novel gene encoding 15-oxoprostaglandin-Delta13
      reductase (PGR-2), which catalyzes the reaction converting 15-keto-PGE2 to 13,14
      dihydro-15-keto-PGE2. The expression of PGR-2 is up-regulated in the late phase
      of 3T3-L1 adipocyte differentiation and predominantly distributed in adipose
      tissue. Overexpression of PGR-2 in cells decreases peroxisome proliferator
      activated receptor gamma (PPARgamma)-dependent transcription and prohibits 3T3-L1
      adipocyte differentiation without affecting expression of PPARgamma.
      Interestingly, we found that 15-keto-PGE2 can act as a ligand of PPARgamma to
      increase co-activator recruitment, thus activating PPARgamma-mediated
      transcription and enhancing adipogenesis of 3T3-L1 cells. Overexpression of 15
      hydroxyprostaglandin dehydrogenase, which catalyzes the oxidation reaction of
      PGE2 to form 15-keto-PGE2, significantly increased PPARgamma-mediated
      transcription in a PGE2-dependent manner. Reciprocally, overexpression of wild
      type PGR-2, but not the catalytically defective mutant, abolished the effect of
      15-keto-PGE2 on PPARgamma activation. These results demonstrate a novel link
      between catabolism of PGE2 and regulation of ligand-induced PPARgamma activation.

PMID- 17449870
TI  - Photooxidation generates biologically active phospholipids that induce heme
      oxygenase-1 in skin cells.
AB  - Heme oxygenase-1 (HO-1) is a key enzyme in the cellular response to tissue injury
      and oxidative stress. HO-1 enzymatic activity results in the formation of the
      cytoprotective metabolites CO and biliverdin. In the skin, HO-1 is strongly
      induced after long wave ultraviolet radiation (UVA-1). Here we show that UVA-1
      irradiation generates oxidized phospholipids derived from 1-palmitoyl-2
      arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC) that mediate the expression of
      HO-1 in skin cells. Using EO6 antibodies that recognize oxidized phospholipids,
      we show that UVA-1 irradiation of dermal fibroblasts generates oxidation-specific
      epitopes. Irradiation of arachidonate-containing phospholipids with UVA-1 led to
      formation of defined lipid oxidation products including epoxyisoprostane
      phosphatidylcholine that induced HO-1 expression in dermal fibroblasts, in
      keratinocytes, and in a three-dimensional epidermal equivalent model. In
      addition, we demonstrate that the oxidation of PAPC by UVA-1 is a singlet oxygen
      dependent mechanism. Together, we present a novel mechanism of UVA-1-induced HO-1
      expression that is mediated by the generation of biologically active phospholipid
      oxidation products. Because UVA-1 irradiation is a mainstay treatment of several
      inflammatory skin diseases, structural identification of UVA-1-generated
      biomolecules with HO-1-inducing capacity should lead to the development of drugs
      that could substitute for irradiation.

PMID- 17449871
TI  - Expression of the rat sterol regulatory element-binding protein-1c gene in
      response to insulin is mediated by increased transactivating capacity of
      specificity protein 1 (Sp1).
AB  - The induction of genes involved in lipid biosynthesis by insulin is mediated in
      part by the sterol regulatory element-binding protein-1c (SREBP-1c). SREBP-1c is
      directly regulated by insulin by transcriptional and post-transcriptional
      mechanisms. Previously, we have demonstrated that the insulin-responsive cis
      acting unit of the rat SREBP-1c promoter is composed of several elements that
      include a sterol regulatory element, two liver X receptor elements, and a number
      of conserved GC boxes. Here we systematically dissected the role of these GC
      boxes and report that five bona fide Sp1-binding elements of the SREBP-1c
      promoter determine its basal and insulin-induced activation. Luciferase
      expression driven by the rat SREBP-1c promoter was accelerated by ectopic
      expression of Sp1, and insulin further enhanced the transactivation potential of
      Sp1. Introduction of a small interfering RNA against Sp1 reduced both basal and
      insulin-induced activation of the SREBP-1c promoter. We also found that Sp1
      interacted with both SREBP-1c and LXRalpha proteins and that insulin promoted
      these interactions. Chromatin immunoprecipitation studies revealed that insulin
      facilitated the recruitment of the steroid receptor coactivator-1 to the SREBP-1c
      promoter. These studies identify a novel mechanism by which maximal activation of
      the rat SREBP-1c gene expression by insulin is mediated by Sp1 and its enhanced
      ability to interact with other transcriptional regulatory proteins.

PMID- 17449872
TI  - Selective perturbation of the myosin recovery stroke by point mutations at the
      base of the lever arm affects ATP hydrolysis and phosphate release.
AB  - After ATP binding the myosin head undergoes a large structural rearrangement
      called the recovery stroke. This transition brings catalytic residues into place
      to enable ATP hydrolysis, and at the same time it causes a swing of the myosin
      lever arm into a primed state, which is a prerequisite for the power stroke. By
      introducing point mutations into a subdomain interface at the base of the myosin
      lever arm at positions Lys(84) and Arg(704), we caused modulatory changes in the
      equilibrium constant of the recovery stroke, which we could accurately resolve
      using the fluorescence signal of single tryptophan Dictyostelium myosin II
      constructs. Our results shed light on a novel role of the recovery stroke: fine
      tuning of this reversible equilibrium influences the functional properties of
      myosin through controlling the effective rates of ATP hydrolysis and phosphate
      release.

PMID- 17449873
TI  - Cold agglutinin disease revealing mediastinal seminoma.

PMID- 17449874
TI  - Childhood abuse, adult alcohol use disorders and suicidal behaviour.
AB  - Childhood abuse is linked to a variety of maladaptive outcomes that can extend
      far into adulthood. Two of the most significant are alcohol use disorders and
      suicidal ideation/behaviour. This article explores the pathway from childhood
      abuse to suicidal behaviour through the development of alcohol use disorders, and
      examines the significance of a familial history of alcohol misuse in exacerbating
      suicidal behaviour in adults who were abused as children. It discusses the
      implications of this pathway, and describes areas of focus for those who work
      with child abuse victims and/or patients experiencing alcohol use disorders.
      Practitioners working with children or adolescents who have experienced or are
      experiencing abuse should take a preventative approach, identifying and treating
      those at risk for alcohol misuse and/or suicide. Practitioners working with
      adults who are already abusing alcohol and/or are suicidal should work with the
      adult to identify and examine life events such as abuse that may be responsible.
      By identifying factors that have led to the misuse of alcohol and/or suicidal
      ideation, adults can obtain appropriate psychotherapy and deal in a more
      productive and beneficial manner with the pain that underlies their self
      destructive impulses.

PMID- 17449875
TI  - Economic analysis of treatments reducing coronary heart disease mortality in
      England and Wales, 2000-2010.
AB  - BACKGROUND: Coronary heart disease (CHD) in the UK affects approximately 3
      million people, with >100,000 deaths annually. Mortality rates have halved since
      the 1980s, but annual NHS treatment costs for CHD exceed 2 billion pounds. AIM:
      To examine the cost-effectiveness of specific CHD treatments in England and
      Wales. METHODS: The IMPACT CHD model was used to calculate the number of life
      years gained (LYG) from specific cardiological interventions from 2000 to 2010.
      Cost-effectiveness ratios (costs per LYG) were generated for each specific
      intervention, stratified by age and sex. The robustness of the results was tested
      using sensitivity analyses. RESULTS: In 2000, medical and surgical treatments
      together prevented or postponed approximately 25,888 deaths in CHD patients aged
      25-84 years, thus generating approximately 194,929 extra life-years between 2000
      and 2010 (range 143,131-260,167). Aspirin and beta-blockers for secondary
      prevention following myocardial infarction or revascularisation, for angina and
      heart failure were highly cost-effective (< 1000 pounds per LYG). Other secondary
      prevention therapies, including cardiac rehabilitation, ACE inhibitors and
      statins, were reasonably cost-effective (1957 pounds, 3398 pounds and 4246 pounds
      per LYG, respectively), as were CABG surgery (3239 pounds-4601 pounds per LYG)
      and angioplasty (3845 pounds-5889 pounds per LYG). Primary angioplasty for
      myocardial infarction was intermediate (6054 pounds-12,057 pounds per LYG,
      according to age), and statins in primary prevention were much less cost
      effective (27,828 pounds per LYG, reaching 69,373 pounds per LYG in men aged 35
      44). Results were relatively consistent across a wide range of sensitivity
      analyses. DISCUSSION: The cost-effectiveness ratios for standard CHD treatments
      varied by over 100-fold. Large amounts of NHS funding are being spent on
      relatively less cost-effective interventions, such as statins for primary
      prevention, angioplasty and CABG surgery. This merits debate.

PMID- 17449876
TI  - First experience with a new active fixation coronary sinus lead.
AB  - AIMS: Coronary sinus (CS) lead implantation is a technically challenging
      procedure owing to variable vein anatomies and a high dislocation rate.
      Therefore, CS lead technology has undergone evolutionary changes during the last
      10 years. The mode of fixation has been a passive one up to now. We want to
      describe our first clinical experience with the newly available active fixation
      lead 4195 in terms of dislocation rate and stability of thresholds compared with
      conventional models. METHODS AND RESULTS: From 1999 to February 2007, we
      implanted 403 CS leads in 368 patients. Leads were categorized into three
      different groups on the basis of their fixation mechanism: straight (Easytrak I
      and Situs OTW; n = 54), curved (Attain 4193 and 4194, Corox, Aescula, Situs ULD;
      n = 308), and active (Attain 4195; n = 41). Operative and follow-up data were
      prospectively noted and checked for significance between groups during the first
      3 months after implantation. Kaplan-Meier analysis of long-term lead function was
      also performed. Straight and curved CS leads suffered from significantly more
      dislocations compared with active fixation (P < 0.001). The active fixation lead
      (4195) has a stable threshold over time compared with a significant rise after 24
      h and thereafter in straight (62%) and curved leads (20%). However, retraction of
      an active fixation CS lead may be a difficult issue as outlined in two cases
      requiring pullback of a 4195 lead owing to phrenic nerve stimulation (one
      unsuccessful despite vigorous traction). CONCLUSION: The active fixation lead
      4195 using retention lobes yielded stable thresholds over time and seems to be
      superior to conventional leads in terms of dislocation. However, extraction may
      be a difficult or even impossible task.

PMID- 17449877
TI  - Echocardiographic measures of acute haemodynamic response after cardiac
      resynchronization therapy predict long-term clinical outcome.
AB  - AIMS: Although acute haemodynamic improvement in response to cardiac
      resynchronization therapy (CRT) is reflective of a favourable cardiac contractile
      response, there is limited information regarding not only its ability to predict
      long-term clinical outcome but also cardiac-substrate-specific differences in the
      prognostic value of this measure. METHODS AND RESULTS: Fifty-three heart failure
      patients (69 +/- 11 years) with low left ventricle ejection fraction (LVEF) (22
      +/- 6%), wide QRS (169 +/- 31 ms), and indications for CRT were included. There
      were no significant differences in age, New York Heart Association (NYHA) class,
      medications, QRS width, or LVEF between ischaemic (n = 37) and non-ischaemic (n =
      16) groups. Echocardiograms were performed within 24 h of implantation with
      device OFF and ON. Acute haemodynamic response was measured as LV dP/dt derived
      from the CW Doppler of mitral regurgitation. Percentage change in dP/dt was used
      to classify patients: high- (HR: DeltadP/dt > 25%) or poor-responders (PR:
      DeltadP/dt <or= 25%). Clinical response to CRT was defined by a combined endpoint
      of hospitalizations and all-cause mortality at 12 months. HR group had a
      significantly better outcome compared to the PR group (P-value = 0.004)
      irrespective of the aetiology of the cardiomyopathy. CONCLUSION:
      Echocardiographic assessment of the acute haemodynamic response to CRT predicts
      long-term clinical outcome in both ischaemic and non-ischaemic cardiomyopathy.

PMID- 17449878
TI  - Relationship between circulating endothelial cells and the predicted risk of
      cardiovascular events in acute coronary syndromes.
AB  - AIMS: The quantification of circulating endothelial cells (CECs) in whole blood
      is a novel marker of direct endothelial injury and shows promise as a potential
      biomarker of cardiovascular (CV) risk. The inter-relationship(s) between CECs and
      predicted CV risk has not been explored in large cohort of 'high-risk' patients.
      We hypothesized that there would be a significant relationship between increasing
      CEC counts and predicted CV risk in a broad spectrum of patients presenting with
      acute coronary syndrome (ACS). METHODS AND RESULTS: We studied 197 patients (aged
      40-80 years) admitted with a confirmed diagnosis of unstable angina (UA), non-ST
      elevation myocardial infarction (MI, NSTEMI), or ST-elevation MI (STEMI). CEC
      counts were performed on venous whole blood using the immunobead technique. Four
      well-validated ACS risk scores [(PURSUIT and TIMI for NSTEMI/UA) TIMI (STEMI) and
      GRACE (all ACS)] were calculated from the initial clinical history and
      electrocardiogram, as well as from values of laboratory parameters collected
      within 12 h of admission. We included a healthy control (HC) group of 50 matched
      patients in order to quantify the accuracy of CEC counts for the diagnosis of ACS
      and to compare disease vs. HC counts. CEC counts were significantly higher in the
      disease group when compared with the HC group. CEC counts significantly increased
      with increasing severity of disease (that is, UA vs. NSTEMI vs. STEMI; P =
      0.002). CEC counts were higher among patients with clinical evidence of heart
      failure (Killip Class II-IV) when compared with those without (Killip Class I) on
      admission (P < 0.0001). There was a significant correlation between CEC counts
      and predicted CV risk for each of the four ACS risk scoring schemes (all P <
      0.05). The area under the receiver-operating characteristic (ROC) curve (AUC) for
      the entire ACS cohort was 0.82 (95% CI: 0.76-0.88; P < 0.0001). A CEC count of
      >or=7/mL provided a positive predictive value of 90.6% (95% CI: 85.6-95.7%) and a
      negative predictive value of 53.5% (41.9-65.1%) for the diagnosis of MI
      (NSTEMI/STEMI) in the presence of an appropriate clinical presentation.
      CONCLUSION: There is a significant and positive correlation between increasing
      CECs and increasing CV risk in ACS. The diagnostic accuracy of CECs in this
      setting is only 'moderate'. Whilst it is good at confirming the presence of MI, a
      CEC value of <7.0/mL is less reliable at confidently excluding patients without
      disease.

PMID- 17449879
TI  - Vaginoplasty using autologous in vitro cultured vaginal tissue in a patient with
      Mayer-von-Rokitansky-Kuster-Hauser syndrome.
AB  - Mayer-von-Rokitansky-Kuster-Hauser syndrome (MRKHS) is characterized by vaginal
      agenesis with variable Mullerian duct abnormalities. The Abbe-McIndoe technique
      is considered a valid treatment option for vaginoplasty but no consensus has been
      reached on what material should be used for the neovagina canal wall lining. We
      report the first case of autologous vaginal tissue transplantation in a 28-year
      old women with MRKHS. The patient was subjected to a 1 cm2 full-thickness mucosal
      biopsy from the vaginal vestibule. Following enzymatic dissociation, cells were
      inoculated onto collagen IV-coated plates and cultured for 2 weeks. The patient
      was subjected to a vaginoplasty with a modified Abbe-McIndoe vaginoplasty with
      314 cm2 autologous in vitro cultured vaginal tissue for the canal lining. At 1
      month from surgery, the vagina appeared normal in length and depth and a vaginal
      biopsy revealed normal vaginal tissue. The use of autologous in vitro cultured
      vaginal tissue to create a neovagina appears as an easy, minimally invasive and
      useful method.

PMID- 17449880
TI  - Fertility-preserving treatment with progestin, and pathological criteria to
      predict responses, in young women with endometrial cancer.
AB  - BACKGROUND: There are therapeutic dilemmas regarding conservative management of
      endometrial cancer in young women. METHODS: We planned a prospective study to
      conservatively treat women aged under 40 years with clinical stage 1A, grade 1
      endometrioid adenocarcinoma from 1999 to 2005. There were nine women (aged 28-40)
      who fulfilled the criteria, and medroxyprogesterone acetate (400 mg/day) was
      continued for 6 months. Curettage materials were pathologically evaluated
      according to our criteria including partial response (PR) (a small amount of
      cancer tissue with remarkable hormonal effects or atypical hyperplasia). To
      predict complete response (CR) to progestin, immunohistochemical staining for
      insulin-like growth factor type 1 receptor, phosphatase and tensin homolog
      deleted on chromosome ten, progesterone receptor (PgR), estrogen receptor and
      Ki67 were assessed. RESULTS: Seven (78%) and two cases presented complete and
      PRs, respectively. Two patients developed recurrent disease 10 and 22 months
      after the last dilatation and curettage, and both had synchronous ovarian cancer.
      However, all nine patients were alive and disease-free for a mean of 39 months.
      Of eight married patients, four (50%) conceived and three delivered full-term
      singletons. CR was related to positive expression of PgR (P=0.008). CONCLUSIONS:
      Patients with an initial PR can obtain CR after further treatment, and the PgR
      may be useful in predicting CR to fertility-preserving treatment in young women
      with endometrial cancer.

PMID- 17449881
TI  - Adverse drug reactions related to amoxicillin alone and in association with
      clavulanic acid: data from spontaneous reporting in Italy.
AB  - OBJECTIVES: To analyse an Italian database of spontaneous reporting of suspected
      adverse drug reactions in order to compare the safety profile of amoxicillin and
      amoxicillin/clavulanic acid. METHODS: Data were retrieved from the spontaneous
      reports collected by six Italian regions (the GIF database) from January 1988 to
      June 2005. Drug utilization data were also available for the two drugs. The
      comparison between amoxicillin and amoxicillin/clavulanic acid was made using the
      chi(2) or Student's t-test, when appropriate. Disproportionality in reporting of
      adverse events was assessed using reporting odds ratio methodology. RESULTS: Up
      to June 2005, the GIF database collected 37 906 reports, of which 1088 were
      related to amoxicillin/clavulanic acid and 1095 to amoxicillin. The percentage of
      skin reactions was statistically higher for amoxicillin (82%) than for
      amoxicillin/clavulanic acid (76%); on the contrary, the percentage of
      gastrointestinal, hepatic and haematological reactions was significantly higher
      for amoxicillin/clavulanic acid (13%, 4% and 2%, respectively) than for
      amoxicillin (7%, 1% and 1%, respectively). Amoxicillin/clavulanic acid seems to
      be associated with a higher risk of Stevens-Johnson syndrome, purpura and
      hepatitis than amoxicillin alone. In particular, the reporting rate of hepatitis
      is on average 9-fold higher for amoxicillin/clavulanic acid than for amoxicillin.
      CONCLUSIONS: Analysis shows a different safety profile for the two selected
      drugs. The combination of amoxicillin/clavulanic acid has been increasingly used
      in Italy and now represents the most frequently antibiotic prescribed by Italian
      general practitioners. Given the documented level of inappropriate use of beta
      lactams in Italy, these results should be taken into account by physicians before
      prescribing amoxicillin/clavulanic acid to patients.

PMID- 17449882
TI  - Molecular mechanisms of resistance to antibiotics in Bartonella bacilliformis.
AB  - OBJECTIVES: Bartonella bacilliformis is the aetiological agent of Carrion's
      disease. Although ciprofloxacin, rifampicin and erythromycin have been
      successfully used in the treatment of the disease, failures and relapses have
      been reported. The objective of our study was to select in vitro mutants
      resistant to antibiotics in order to determine the frequency of mutations and to
      characterize the mechanism of resistance at the molecular level. METHODS:
      Antibiotic-resistant mutants were selected by serial passages of bacteria on
      blood agar plates containing antibiotics. Candidate genes involved in resistance
      were amplified and sequenced and compared in order to look at mutations
      associated with antibiotic resistance. RESULTS: Ciprofloxacin-, rifampicin- and
      erythromycin-resistant mutants were obtained after five, three and four passages,
      respectively. Conversely, no mutant was obtained with either gentamicin or
      doxycycline even after 16 passages. The ciprofloxacin mutant contained an amino
      acid change at position 87 (Asp --> Asn) in its quinolone resistance-determining
      region of the DNA gyrase protein, whereas the rifampicin-resistant strain had an
      amino acid change at position 531 (Ser --> Phe) in the rifampicin resistance
      determining region of the rpoB gene. Similarly, the erythromycin-resistant mutant
      showed an A2058G mutation in the 23S rRNA gene. CONCLUSIONS: According with the
      current knowledge on the treatment of human bartonellosis, we believe that
      doxycycline in association with gentamicin may be the preferred regimen for the
      treatment of the acute and eruptive stages of Carrion's disease, but clinical
      trials are warranted to support our findings.

PMID- 17449883
TI  - Prediction of specific pathogens in patients with sepsis: evaluation of TREAT, a
      computerized decision support system.
AB  - BACKGROUND: Prediction of bacterial infections and their pathogens allows for
      early, directed investigation and treatment. We assessed the ability of TREAT, a
      computerized decision support system, to predict specific pathogens. METHODS:
      TREAT uses data available within the first few hours of infection presentation in
      a causal probabilistic network to predict sites of infection and specific
      pathogens. We included 3529 patients (920 with microbiologically documented
      infections) participating in the observational and interventional trials of the
      TREAT system in Israel, Germany and Italy. Discriminatory performance of TREAT to
      predict individual pathogens was expressed by the AUC with 95% confidence
      intervals. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit
      statistic. RESULTS: The AUCs for Gram-negative bacteria, including Pseudomonas
      aeruginosa, Acinetobacter baumannii, Klebsiella spp. and Escherichia coli, ranged
      between 0.70 and 0.80 (all significant). Adequate calibration was demonstrated
      for any Gram-negative infection and individual bacteria, except for E. coli.
      Discrimination and calibration were acceptable for Enterococcus spp. (AUC 0.71,
      0.65-0.78), but not for Staphylococcus aureus (AUC 0.63, 0.55-0.71). The few
      infections caused by Candida spp. and Clostridium difficile were well predicted
      (AUCs 0.74, 0.54-0.95; and 0.94, 0.88-1.00, respectively). The coverage with
      TREAT's recommendation exceeded that observed with physicians' treatment for all
      pathogens, except Candida spp. CONCLUSIONS: TREAT predicted individual pathogens
      causing infection well. Prediction of S. aureus was inferior to that observed
      with other pathogens. TREAT can be used to triage patients by the risk for
      specific pathogens. The system's predictions enable it to prescribe appropriate
      antibiotic treatment prior to pathogen identification.

PMID- 17449884
TI  - Resveratrol inhibition of Propionibacterium acnes.
AB  - OBJECTIVES: To evaluate the effects of the anti-inflammatory hydroxystilbene,
      resveratrol, on Propionibacterium acnes growth. METHODS: Three different strains
      of P. acnes were tested against resveratrol at concentrations between 0 and 200
      mg/L. Piceatannol was included as a second hydroxystilbene to compare with
      resveratrol, and erythromycin and benzoyl peroxide were used as positive
      controls. RESULTS: After 24 h of treatment with resveratrol, the average 50%
      inhibitory concentration (IC(50)) was 73 mg/L and the average 100% inhibitory
      concentration (IC(100)) was 187 mg/L for the three strains of P. acnes tested.
      The IC(50) and IC(100) of piceatannol were 123 and 234 mg/L, respectively. The
      highest concentration of resveratrol tested (200 mg/L) was bactericidal, whereas
      lower concentrations were bacteriostatic. CONCLUSIONS: Resveratrol, an anti
      inflammatory hydroxystilbene, is capable of inhibiting P. acnes growth.

PMID- 17449885
TI  - Short peptides derived from the NH2-terminus of subclass IIa bacteriocin
      enterocin CRL35 show antimicrobial activity.
AB  - OBJECTIVES: Subclass IIa bacteriocins are characterized by a hydrophilic N
      terminal domain that shares a YGNGVxCxxxxC consensus and a variable hydrophobic C
      terminus. Enterocin CRL35 is a 43-amino-acid heat stable peptide with
      antilisterial activity. Short synthetic peptides derived from the N-terminal half
      of enterocin CRL35 and other subclass IIa bacteriocins were evaluated for
      antimicrobial properties. METHODS: In vitro activities of synthetic peptides were
      evaluated in complex, chemically defined and minimal media. MIC assays were
      performed by the agar well-diffusion method. Fluorescence assays to evaluate the
      dissipation of membrane potentials in intact cells were carried out. Time-kill
      kinetics of Listeria innocua cells with the active peptide were performed.
      RESULTS AND CONCLUSIONS: A 15-mer peptide derived from enterocin CRL35 inhibited
      the growth of L. innocua and Listeria monocytogenes in synthetic/minimal media
      and dissipated the membrane potential of sensitive cells, with MICs of 10 and 50
      microM, respectively. 15-mer derivatives from other class IIa bacteriocins
      (mesentericin Y105, pediocin PA-1 and piscicolin 126) also showed antimicrobial
      activities.

PMID- 17449886
TI  - Travel-acquired salmonellosis due to Salmonella Kentucky resistant to
      ciprofloxacin, ceftriaxone and co-trimoxazole and associated with treatment
      failure.

PMID- 17449887
TI  - An observational study of empirical antibiotics for adult women with
      uncomplicated UTI in general practice.
AB  - OBJECTIVES: Women presenting in primary care with symptoms suggestive of
      uncomplicated urinary tract infection (UTI) are commonly managed without urine
      culture. We therefore do not know how successful general practitioners (GPs) are
      at targeting antibiotic treatment to women who would have had a microbiologically
      confirmed UTI, or at avoiding antibiotics in those who would have had a negative
      culture, had all patients with a suspected UTI been sampled. We therefore
      explored the association between antibiotic prescribing and urine culture results
      when culture was performed in all symptomatic patients. METHODS: GPs in nine
      general practices in South Wales were asked to submit urine specimens from all
      women consulting with clinically suspected, uncomplicated UTI. Patients were
      followed up 2 weeks later by questionnaire. RESULTS AND CONCLUSIONS: One hundred
      and thirteen adult women with a median age of 54 years were included and 61%
      received empirical antibiotics. There was very low agreement between the decision
      to prescribe empirically and subsequent culture result (Kappa = 0.04), with 60%
      of those prescribed empirical antibiotics subsequently found to have a negative
      culture, and 25% of those found to have a positive culture not prescribed
      empirical antibiotics. Current strategies to target empirical antibiotic
      prescribing in clinically suspected, uncomplicated UTI require review.

PMID- 17449888
TI  - Public attitudes towards bacterial resistance: a qualitative study.
AB  - OBJECTIVES: Behaviour of members of the public contributes to bacterial
      resistance. For behavioural change to occur, individuals need to perceive the
      issue as important to them and feel able to make a valuable contribution. Public
      campaigns have, so far, not been informed by detailed understanding of public
      attitudes to the problem. We therefore set out to explore the attitudes of
      members of the public to bacterial resistance. METHODS: A qualitative grounded
      theory interview study was undertaken. A purposive maximum variation sample
      included 32 (70%) women and 14 (30%) men, aged from 18 to 89 years, from areas of
      high, average and low deprivation. RESULTS: Participants were uncertain about
      bacterial resistance and their explanations were generally incongruent with
      prevailing biomedical concepts. Perceived importance and personal threat were
      low. The media was the main information source and it left the impression that
      dirty hospitals are the main cause. Some participants dreaded hospitalization
      because they feared resistant infections. Few recognized resistant infections as
      a problem in the community. Less than a quarter indicated that they could
      positively influence the situation by expecting antibiotic prescriptions less
      often, or taking antibiotics according to instructions, and even fewer through
      their own hand washing behaviour. CONCLUSIONS: Although members of the public can
      contribute to containing bacterial resistance, most do not feel that they have a
      personal role in either the problem or its solution. Campaigns should identify
      bacterial resistance as both a hospital and a community problem that individuals
      have the power to influence through specific actions.

PMID- 17449889
TI  - In vitro and in vivo antibacterial evaluation of DRF 8417, a new oxazolidinone.
AB  - OBJECTIVES AND METHODS: DRF 8417, a novel oxazolidinone, has been evaluated
      against Gram-positive and fastidious Gram-negative bacteria. In vitro activity of
      DRF 8417 was determined by broth microdilution method and in vivo efficacy
      studies were carried out in different murine systemic infection models. RESULTS:
      DRF 8417 exhibited potent activity against Gram-positive pathogens with MIC(50)
      and MIC(90) values ranging from 0.06 to 1 mg/L. MICs against Haemophilus
      influenzae and Moraxella catarrhalis were one to two dilutions lower than those
      of linezolid. The in vivo efficacy, by oral route, in different susceptible and
      resistant Gram-positive systemic bacterial infection models ranged from 2.0 to
      2.9 mg/kg. CONCLUSIONS: These studies displayed the excellent in vitro and in
      vivo activity of DRF 8417 against Gram-positive pathogens and lower MICs when
      compared with linezolid against H. influenzae and M. catarrhalis.

PMID- 17449890
TI  - Ultrasonographic guidance for sciatic and femoral nerve blocks in children.
AB  - BACKGROUND: Recent studies have shown that ultrasound guidance for paediatric
      regional anaesthesia can improve the quality of upper extremity and neuraxial
      blocks. We therefore investigated whether ultrasound guidance for sciatic and
      femoral nerve blocks prolongs sensory blockade in comparison with nerve
      stimulator guidance in children. METHODS: Forty-six children scheduled for
      surgery of one lower extremity were randomized to receive a sciatic and femoral
      nerve block under either ultrasound or nerve stimulator guidance. After induction
      of general anaesthesia, the blocks were performed using an ultrasound-guided
      multiple injection technique until the nerves were surrounded by levobupivacaine,
      or by nerve stimulator guidance using a predefined dose of 0.3 ml kg(-1) of
      levobupivacaine. An increase in heart rate of more than 15% of baseline during
      surgery defined a failed block. The duration of the block was determined from the
      injection of local anaesthetic to the time when the patient received the first
      postoperative analgesic. RESULTS: Two blocks in the nerve stimulator group
      failed. There were no failures in the ultrasound group. The duration of analgesia
      was longer in the ultrasound group mean (sd) 508 (178) vs 335 (169) min (P <
      0.05). The volume of local anaesthetic in sciatic and femoral nerve blocks was
      reduced with ultrasound compared with nerve stimulator guidance [0.2 (0.06) vs
      0.3 ml kg(-1) (P < 0.001) and 0.15 (0.04) vs 0.3 ml kg(-1) (P < 0.001),
      respectively]. CONCLUSIONS: Ultrasound guidance for sciatic and femoral nerve
      blocks in children increased the duration of sensory blockade in comparison with
      nerve stimulator guidance. Prolonged sensory blockade was achieved with smaller
      volumes of local anaesthetic when using ultrasound guidance.

PMID- 17449891
TI  - Motor vehicle crash injury rates by mode of travel, United States: using exposure
      based methods to quantify differences.
AB  - The authors used traffic exposure data to calculate exposure-based fatal and
      nonfatal traffic injury rates in the United States. Nationally representative
      data were used to identify fatal and nonfatal traffic injuries that occurred from
      1999 to 2003, and the 2001 National Household Travel Survey was used to estimate
      traffic exposure (i.e., person-trips). Fatal and nonfatal traffic injury rates
      per 100 million person-trips were calculated by mode of travel, sex, and age
      group. The overall fatal traffic injury rate was 10.4 per 100 million person
      trips. Fatal injury rates were highest for motorcyclists, pedestrians, and
      bicyclists. The nonfatal traffic injury rate was 754.6 per 100 million person
      trips. Nonfatal injury rates were highest for motorcyclists and bicyclists.
      Exposure-based traffic injury rates varied by mode of travel, sex, and age group.
      Motorcyclists, pedestrians, and bicyclists faced increased injury risks. Males,
      adolescents, and the elderly were also at increased risk. Effective interventions
      are available and should be implemented to protect these vulnerable road users.

PMID- 17449892
TI  - Body mass and colorectal cancer risk in the NIH-AARP cohort.
AB  - In most studies, body mass index (BMI) has been associated with increased risk of
      colorectal or colon cancer in men, but the relation is weaker and less consistent
      for women, possibly because of interactions with age or hormone replacement
      therapy. The authors examined the relation between BMI and colorectal cancer
      incidence in a large, prospective US cohort of 307,708 men and 209,436 women from
      the NIH-AARP Diet and Health Study. During follow-up of the cohort from 1995 to
      2000, 2,314 cases of colorectal cancer were observed in men and 1,029 in women.
      BMI was related to increased risk of incident colon cancer, but not rectal
      cancer, for both men and women. For men, relative risks of colon cancer for a BMI
      of 18.5-<23, 23-<25, 25-<27.5, 27.5-<30, 30-<32.5, 32.5-<35, 35-<40, and > or =
      40 kg/m(2) were 1.0 (referent), 1.11, 1.22, 1.44, 1.53, 1.57, 1.71, and 2.39,
      respectively (95% confidence interval: 1.59, 3.58; p-trend < 0.0005).
      Corresponding relative risks for women were 1.0, 1.20, 1.29, 1.31, 1.28, 1.13,
      1.46, and 1.49 (95% confidence interval: 0.98, 2.25; p-trend = 0.02). BMI was
      related to colon cancer risk for younger (aged 50-66 years) but not older (aged
      67-71 years) women. The association was not modified by hormone replacement
      therapy in women or physical activity in men or women.

PMID- 17449893
TI  - Designing an integrated follow-up programme for people treated for cutaneous
      malignant melanoma: a practical application of the MRC framework for the design
      and evaluation of complex interventions to improve health.
AB  - BACKGROUND: Complex health care interventions are difficult to design and
      evaluate, so the UK Medical Research Council (MRC) has developed a 'framework for
      the design and evaluation of complex health care intervention'. Researchers
      differ in applying the framework. OBJECTIVE: To describe and critically evaluate
      how the two initial phases of the MRC framework facilitate the design of an
      integrated follow-up programme for cutaneous melanoma to a standard suitable for
      testing in an exploratory randomized trial. Design of study. Literature review,
      expert groups, semi-structured interviews and pilot exercise to develop an
      intervention. SETTING: A department of academic primary care. Two general
      practices. METHODS: Four techniques were used-iterative literature review, a
      steering group, semi-structured telephone interviews and an operationalization
      exercise. These techniques were used simultaneously and iteratively to complete
      the theoretical preclinical and phase I modelling of the MRC framework when
      developing an integrated follow-up programme for cutaneous melanoma. RESULTS:
      Components of an integrated follow-up programme for cutaneous malignant melanoma
      were identified, developed and refined into a practical intervention comprising
      GP training; structured protocol-driven appointments; a centralized recall
      system; a rapid access pathway and a patient information booklet. Several
      barriers that could have derailed the successful implementation of the
      intervention, including the different perspectives of stakeholders and resource
      needs in general practice were identified. The value of the principles of the
      initial two phases of the MRC framework in guiding the development of complex
      health care interventions was supported. CONCLUSIONS: We recommend that the first
      two phases of the MRC framework be used iteratively and simultaneously when
      developing complex health care interventions.

PMID- 17449894
TI  - Comparisons of site- and haplotype-frequency methods for detecting positive
      selection.
AB  - In this report, we compare the differences between various site- and haplotype
      frequency tests in their power to detect positive selection by doing computer
      simulations. Our results are the following. 1) Although haplotype-frequency tests
      that are conditional on the number of haplotypes (K) were developed for
      nonrecombining haplotypes, these tests are insensitive to recombination. Such
      tests, including the Ewens-Watterson (EW) test, can therefore be applied to
      recombining haplotypes. 2) Tests conditional on the number of segregating sites
      (S) become overly conservative in the presence of recombination. 3) The EW test
      is usually the most powerful test during the sweep phase, especially when the
      local recombination rate is high. 4) The "extended haplotype homozygosity" test
      relies heavily on the prior knowledge of the target of selection. With that
      knowledge, it is the most powerful test, whereas in the absence of this prior
      information, the test has little power. We also study the sensitivities of the
      haplotype-frequency tests to background selection and various demographic forces.
      We find that these tests are sensitive to some forces other than positive
      selection. To alleviate the problem of low specificity, compound tests, such as
      the DH test (Zeng et al. 2006), may be a solution. In the companion paper (Zeng
      K, Shi S, Wu C-I, in preparation), we use the EW test to devise 2 compound tests,
      which are more powerful in detecting positive selection than DH, but are also
      relatively insensitive to demography.

PMID- 17449895
TI  - A family matter: conclusive resolution of the taxonomic position of the long
      fingered bats, miniopterus.
AB  - The long-fingered bats (Miniopterus sp.) are among the most widely distributed
      mammals in the world. However, despite recent focus on the systematics of these
      bats, their taxonomic position has not been resolved. Traditionally, they are
      considered to be sole members of Miniopterinae, 1 of 5 subfamilies within the
      largest family of bats, the Vespertilionidae. However, this classification has
      increasingly been called into question. Miniopterines differ extensively from
      other vespertilionids in numerous aspects of morphology, embryology, immunology,
      and, most recently, genetics. Recent molecular studies have proposed that the
      miniopterines are sufficiently distinct from vespertilionids that Miniopterinae
      should be elevated to full familial status. However, controversy remains
      regarding the relationship of the putative family, Miniopteridae to existing
      Vespertilionidae and to the closely related free-tailed bats, the Molossidae. We
      report here the first conclusive analysis of the taxonomic position of
      Miniopterus relative to all other bat families. We generated one of the largest
      chiropteran data sets to date, incorporating approximately 11 kb of sequence data
      from 16 nuclear genes, from representatives of all bat families and 2 Miniopterus
      species. Our data confirm the distinctiveness of Miniopterus, and we support
      previous recommendations to elevate these bats to full familial status. We
      estimate that they diverged from all other bat species approximately 49-38 MYA,
      which is comparable to most other bat families. Furthermore, we find very strong
      support from all phylogenetic methods for a sister group relationship between
      Miniopteridae and Vespertilionidae. The Molossidae diverged from these lineages
      approximately 54-43 MYA and form a sister group to the Miniopteridae
      Vespertilionidae clade.

PMID- 17449896
TI  - A method to integrate benchmark dose estimates with genomic data to assess the
      functional effects of chemical exposure.
AB  - The use of genomic technology for assessing health risks associated with chemical
      exposure has significant potential, but its direct application has proven to be
      challenging for the toxicology and risk assessment communities. In this study, a
      method was established for analyzing dose-response microarray data using
      benchmark dose (BMD) calculations and gene ontology (GO) classification. Gene
      expression changes in the rat nasal epithelium following acute formaldehyde
      exposure were used as a case study. The gene expression data were first analyzed
      using a one-way ANOVA to identify genes that showed significant dose-response
      behavior. These genes were then fit to a series of four statistical models
      (linear, second-degree polynomial, third-degree polynomial, and power models) and
      the least complex model that best described the data was selected. The genes were
      matched to their associated GO categories, and the average BMD and benchmark dose
      lower confidence limit (BMDL) were calculated for each GO category. The results
      were used to identify doses at which individual cellular processes were altered.
      For the formaldehyde exposures, the BMD estimates for the GO categories related
      to cell proliferation and DNA damage were similar to those measured in previous
      studies using cell labeling indices and DNA-protein cross-links and consistent
      with the BMD estimated for rat nasal tumors. The method represents a significant
      advance in applying genomic information to risk assessment by allowing a
      comprehensive survey of molecular changes associated with chemical exposure and
      providing the capability to identify reference doses at which particular cellular
      processes are altered.

PMID- 17449897
TI  - Comparison of estimated dietary intake of acrylamide with hemoglobin adducts of
      acrylamide and glycidamide.
AB  - In a study comprising 50 subjects, we investigated the relationship between
      acrylamide (AA) intake from food using food frequency questionnaires and the
      concentration of hemoglobin (Hb) adducts of AA and its genotoxic metabolite
      glycidamide (GA) as a measure of the internal exposure. A method using solid
      phase extraction and liquid chromatography with negative electrospray tandem mass
      spectrometric (MS/MS) detection for the determination of the Hb adducts as
      phenylthiohydantoin derivatives in human blood was developed. The limit of
      quantification for AA- and GA-Hb adducts were 2 and 6 pmol/g globin,
      respectively, and the between-assay precision was below 25%. The estimated
      dietary intake of AA was (median and range) 13.5 microg/day (4.1-72.6) in
      nonsmokers and 18.3 microg/day (7.8-32.0) in smokers. In nonsmokers, males had a
      higher intake than females, 16.6 microg/day (18.6-72.6) and 12.8 microg/day (4.1
      30.2), respectively. Nonsmokers had a median AA and GA adduct concentration of
      36.8 (range 17.9-65.5) and 18.2 (range 6.7-45.6) pmol/g globin, respectively. In
      smokers, the values were 165.8 (98.8-211) and 83.2 (29.1-99.0) pmol/g globin,
      respectively. Using multiple linear regression analysis, a significant positive
      correlation was found between the AA-Hb adduct concentration and the intake of
      chips/snacks and crisp bread. GA-Hb adduct did not correlate with consumption of
      any of the main food groups. Neither AA-Hb nor GA-Hb adduct concentration
      correlated with total dietary intake of AA as calculated from the reported food
      intake. Adduct concentrations did not correlate with 24 h urinary excretion of
      mercapturic acid metabolites of AA and GA in the same subjects reported
      previously.

PMID- 17449898
TI  - Adult hippocampal neural stem/progenitor cells in vitro are vulnerable to the
      mycotoxin ochratoxin-A.
AB  - The common mycotoxin ochratoxin-A (OTA) accumulates in brain, causes oxidative
      stress, and elicits a DNA repair response that varies across brain regions and
      neuronal populations. Neural stem/progenitor cells (NSCs) prepared from
      hippocampus of adult mouse brain were tested for their vulnerability to the toxin
      in vitro. The following measurements were made in NSC cell cultures in both
      proliferation and differentiation media: (1) viability (trypan blue exclusion),
      (2) proliferative activity ([(3)H]-thymidine uptake), (3) the DNA repair response
      (oxyguanosine glycosylase activity), and (4) antioxidative response (superoxide
      dismutase). Cells that had proliferated to 90-100% confluency in the presence of
      epidermal growth factor and basic fibroblast growth factor were induced to
      differentiate by removal of the growth factors. OTA, added to the cultures in
      concentrations of 0.01-100 microg/ml, caused a dose- and time-dependent (6-72 h)
      decrease in viability of both proliferating and differentiating NSC.
      Proliferating NSC exhibited a greater vulnerability to the toxin than
      differentiated neurons despite robust DNA repair and antioxidative responses.
      Preconditioning of NSC with a 12-h incubation with the pro-oxidant diethyl
      maleate increased DNA repair activity and, subsequently, provided a moderate
      degree of neuroprotection. Overall, these results lead to speculation that OTA
      exposure may contribute to impaired hippocampal neurogenesis in vivo, resulting
      in depression and memory deficits, conditions reported to be linked to mycotoxin
      exposure in humans.

PMID- 17449899
TI  - Intelligence, parental depression, and behavior adaptability in deaf children
      being considered for cochlear implantation.
AB  - Cognitive ability and behavioral adaptability are distinct, yet related,
      constructs that can impact childhood development. Both are often reduced in deaf
      children of hearing parents who do not provide sufficient language and
      communication access. Additionally, parental depression is commonly observed due
      to parent-child communication difficulties that can lead to parents' feelings of
      inadequacy and frustration. We sought to assess whether adaptive behavior in deaf
      children was associated with nonverbal intelligence and parental depression.
      Parents of precochlear implant patients seen for neuropsychological assessment
      were administered the Parenting Stress Index and Vineland Behavior Adaptive
      Scales to obtain measures of parental distress and child's behavioral
      adaptability. Precochlear implant patients' cognitive functioning was assessed
      via the Mullen Scales of Early Learning or the Leiter International Performance
      Scale-Revised, depending on the child's age at the time of testing. Regardless of
      age or neurological status, the deaf child's adaptive behavior consistently
      showed a strong relationship with intelligence. Moderate correlation between
      parental depression and the child's adaptive behavior was observed only in the
      younger group. The relationship between parental depression and communication
      subscale was moderated by intelligence for deaf children without neurological
      complications. The findings provide important implications for promoting family
      centered interventions with early communication and language development.

PMID- 17449900
TI  - Interventions to reduce weight gain in schizophrenia.

PMID- 17449901
TI  - Association of the ARLTS1 Cys148Arg variant with sporadic and familial colorectal
      cancer.
AB  - ARLTS1 was recently identified in chromosome 13q14 as a tumor suppressor gene of
      the ADP-ribosylation factor family with pro-apoptotic characteristics.
      Additionally, one of its genetic variants (W149X) was hypothesized to be a
      polymorphism associated with familial cancer. We performed a large case-control
      association study within the EPICOLON project aimed at evaluating the sporadic
      and familial colorectal cancer (CRC) risk associated with ARLTS1 genetic
      variants. Whereas P131L and W149X did not seem to affect CRC risk, C148R did
      show, for the first time in CRC, statistically significant differences between
      cases and controls [odds ratio (OR) = 1.45, 95% confidence interval (95% CI) =
      1.13-1.86, P = 0.003], sporadic cases and controls (OR = 1.59, 95% CI = 1.13
      2.23, P = 0.007) and familial cases and controls (OR = 1.55, 95% CI = 1.10-2.19,
      P = 0.01) in agreement with a hypothetical moderate increase of the cancer risk
      linked to the C148R ARLTS1 variant, both in sporadic and familial CRC cases.

PMID- 17449902
TI  - Genetic variation in TP53 and risk of breast cancer in a population-based case
      control study.
AB  - Whereas germ line missense mutations in the tumor suppressor gene TP53 are
      associated with a marked predisposition to breast cancer, single-nucleotide
      polymorphisms (SNPs) may play a more modest role in breast cancer susceptibility.
      We examined genetic variation in TP53 in relation to breast cancer risk among
      women aged 20-74 years in a population-based case-control study in Wisconsin,
      Massachusetts and New Hampshire. Analyses were conducted separately for in situ
      (176 cases/581 controls) and invasive (1,490 cases/1,291 controls) breast cancer.
      Oral mucosal DNA samples were genotyped for the codon 72 polymorphism in exon 4
      (rs1,042,522), seven intronic SNPs and three SNPs residing in the 3' untranslated
      region (UTR). Logistic regression was used to obtain age- and state-adjusted odds
      ratios for individual SNPs. Haplotypes were reconstructed using PHASE software,
      and the overall association with breast cancer risk was assessed using a global
      score test. None of the 11 individual SNPs or eight common haplotypes were
      significantly related to breast carcinoma in situ risk. Among all women, two
      linked SNPs (D' = 0.99, r(2) = 0.95) on intron 7 (rs12,951,053, rs12,947,788)
      were associated with modest increases in invasive breast cancer risk; however,
      associations were only significant for heterozygous carriers. The data suggested
      that additional variants in the 3' UTR (rs9,894,946), and in two correlated SNPs
      (D' = 0.94, r(2) = 0.81) in introns 6 (rs1,625,895) and 4 (rs2,909,430), were
      associated with reduced invasive breast cancer risk among women aged 50 and
      younger only (P(interaction) < 0.03). These results indicate that common
      variation in the TP53 gene could modify the risk of invasive breast cancer.

PMID- 17449903
TI  - Identification of distinct changes in gene expression after modulation of
      melanoma tumor antigen p97 (melanotransferrin) in multiple models in vitro and in
      vivo.
AB  - Melanoma tumor antigen p97 or melanotransferrin (MTf) is an iron (Fe)-binding
      protein with high homology to serum transferrin. MTf is expressed at very low
      levels in normal tissues and in high amounts in melanoma cells although its
      function remains elusive. To understand the function of MTf, we utilized whole
      genome microarray analysis to examine the gene expression profile of five models
      after modulating MTf expression. These models included two new stably transfected
      MTf hyper-expression models (SK-N-MC neuroepithelioma and LMTK- fibroblasts) and
      one cell type (SK-Mel-28 melanoma) where MTf was down-regulated by post
      transcriptional gene silencing. These findings were compared with alterations in
      gene expression identified using the MTf-/- mice. In addition, the changes
      identified from the microarray data were also assessed in a new model of MTf down
      regulation in SK-Mel-2 melanoma cells. In the cell line models, MTf hyper
      expression led to increased proliferation, whereas MTf down-regulation resulted
      in decreased proliferation. Across all five models of MTf down- and up
      regulation, we identified three genes modulated by MTf. These included ATP
      binding cassette subfamily B member 5, whose change in expression mirrored MTf
      down- or up-regulation. In addition, thiamine triphosphatase and transcription
      factor 4 were inversely expressed relative to MTf levels across all five models.
      The products of these three genes are involved in membrane transport, thiamine
      phosphorylation and proliferation/survival, respectively. This study identifies
      novel molecular targets directly or indirectly regulated by MTf and the potential
      pathways involved in its function, including modulation of proliferation.

PMID- 17449904
TI  - Suppression of N-nitrosobis(2-oxopropyl)amine-induced pancreatic carcinogenesis
      in hamsters by pioglitazone, a ligand of peroxisome proliferator-activated
      receptor gamma.
AB  - Fat intake and obesity are positively correlated with pancreatic cancer in
      humans. N-nitrosobis(2-oxopropyl)amine (BOP) induces pancreatic ductal
      adenocarcinomas limited to Syrian golden hamsters, other rodents not being
      susceptible. In the present study, we found markedly high levels of serum
      triglycerides (TGs) and total cholesterol (TC) in Syrian golden hamsters, but not
      C57BL/6 mice, ICR mice, F344 rats and Wistar rats. Consistent with this,
      lipoprotein lipase (LPL) activities in the liver were lower in hamsters compared
      with mice and rats. To examine effects of pioglitazone, a peroxisome proliferator
      activated receptor gamma (PPARgamma) ligand, on LPL expression, serum lipid
      levels and pancreatic cancer development, 6-week-old female Syrian golden
      hamsters were subcutaneously injected with BOP (10 mg/kg body wt) four times in a
      week and thereafter fed a diet containing 800 p.p.m. pioglitazone for 22 weeks.
      The treatment elevated LPL mRNA expression in the liver and significantly
      improved hyperlipidemia with serum levels of TG and TC being decreased to 62 and
      71%, respectively, of the control values. Concurrently, the incidence and
      multiplicity of pancreatic ductal adenocarcinomas were significantly decreased by
      pioglitazone in comparison with the controls (38 versus 80%, P < 0.01 and 0.55 +/
      0.15 versus 1.37 +/- 0.22, P < 0.01, respectively). The suppression rates were
      greater in invasive adenocarcinomas than non-invasive ones. The incidence of
      cholangiocellular carcinomas was also reduced. Thus, suppression of pancreatic
      adenocarcinoma development by pioglitazone is possibly associated with
      improvement in the serum lipid profile, and hyperlipidemia could be an enhancing
      factor for development of pancreatic cancer in hamsters.

PMID- 17449905
TI  - The Wnt antagonist DICKKOPF-1 gene is induced by 1alpha,25-dihydroxyvitamin D3
      associated to the differentiation of human colon cancer cells.
AB  - The Wnt-beta-catenin pathway is aberrantly activated in most colon cancers.
      DICKKOPF-1 (DKK-1) gene encodes an extracellular Wnt inhibitor that blocks the
      formation of signalling receptor complexes at the plasma membrane. We report that
      1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], the most active vitamin D
      metabolite, increases the level of DKK-1 RNA and protein in human SW480-ADH colon
      cancer cells. This effect is dose dependent, slow and depends on the presence of
      a transcription-competent nuclear vitamin D receptor (VDR). Accordingly,
      1,25(OH)2D3 activates a 2300 bp fragment of the human DKK-1 gene promoter.
      Chromatin immunoprecipitation assays revealed that 1,25(OH)2D3 treatment induced
      a pattern of histone modifications which is compatible with transcriptionally
      active chromatin. DKK-1 is expressed at high level in colon cancer cell lines
      with a differentiated phenotype such as Caco-2 or HT-29. Exogenous expression of
      E-cadherin into SW480-ADH cells results in a strong adhesive phenotype and a 17
      fold increase in DKK-1 RNA. In contrast, an E-cadherin blocking antibody inhibits
      1,25(OH)2D3-induced differentiation of SW480-ADH cells and DKK-1 gene expression.
      Remarkably, in vivo treatment with the vitamin D analogue EB1089 induced DKK-1
      protein expression in SW480-ADH cells xenografted in immunodeficient mice, and a
      correlation was observed in the expression of VDR and DKK-1 RNA in a series of 32
      human colorectal tumours. These data indicate that 1,25(OH)2D3 activates the
      transcription of the DKK-1 gene, probably in an indirect way that is associated
      to the promotion of a differentiated phenotype. DKK-1 gene induction constitutes
      a novel mechanism of inhibition of Wnt signalling and antitumour action by
      1,25(OH)2D3.

PMID- 17449906
TI  - Genetic polymorphisms in one-carbon metabolism: associations with CpG island
      methylator phenotype (CIMP) in colon cancer and the modifying effects of diet.
AB  - This study investigated associations between CpG island methylator phenotype
      (CIMP) colon cancer and genetic polymorphisms relevant to one-carbon metabolism
      and thus, potentially the provision of methyl groups and risk of colon cancer.
      Data from a large, population-based case-control study (916 incident colon cancer
      cases and 1,972 matched controls) were used. Candidate polymorphisms in
      methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS),
      transcobalamin II (TCNII), methionine synthase (MTR), reduced folate carrier
      (RFC), methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), dihydrofolate
      reductase (DHFR) and alcohol dehydrogenase 3 (ADH3) were evaluated. CIMP- or
      CIMP+ phenotype was based on five CpG island markers: MINT1, MINT2, MINT31, p16
      and MLH1. The influence of specific dietary factors (folate, methionine, vitamin
      B(12) and alcohol) on these associations was also analyzed. We hypothesized that
      polymorphisms involved in the provision of methyl groups would be associated with
      CIMP+ tumors (two or more of five markers methylated), potentially modified by
      diet. Few associations specific to CIMP+ tumors were observed overall, which does
      not support the hypothesis that the provision of methyl groups is important in
      defining a methylator phenotype. However, our data suggest that genetic
      polymorphisms in MTHFR 1,298A > C, interacting with diet, may be involved in the
      development of highly CpG-methylated colon cancers. AC and CC genotypes in
      conjunction with a high-risk dietary pattern (low folate and methionine intake
      and high alcohol use) were associated with CIMP+ (OR = 2.1, 95% CI = 1.3-3.4
      versus AA/high risk; P-interaction = 0.03). These results provide only limited
      support for a role of polymorphisms in one-carbon metabolism in the etiology of
      CIMP colon cancer.

PMID- 17449907
TI  - Effects of glucose metabolism on the regulation of genes of fatty acid synthesis
      and triglyceride secretion in the liver.
AB  - Glucose disposal induces a signal that modulates the transcriptional regulation
      of genes involved in the glycolysis and lipogenesis pathways. To investigate the
      role of glucose metabolism on hepatic gene expression independently from insulin
      action, we overexpressed glucokinase, the limiting enzyme in the glycolysis
      pathway, in the liver of streptozotocin-induced type 1 diabetic rats. By
      microarray analysis, we observed that critical genes such as liver-type pyruvate
      kinase, malic enzyme, fatty acid synthase, and stearoyl-CoA desaturase 1 were
      enhanced multiple-fold, whereas genes involved in mitochondrial fatty acid
      oxidation and the Krebs cycle were downregulated. Despite the increase in
      expression of fatty acid synthesis genes and the presence of steatosis, no major
      alterations to the levels of genes involved in VLDL assembly and secretion, such
      as diacylglycerol acyltransferases 1 and 2 and microsomal triglyceride transfer
      protein, were observed. Overall, our data suggest that the gene expression
      pattern induced by glucose metabolism favors fatty acid storage in the liver
      rather than secretion into the circulation.

PMID- 17449908
TI  - Summary of personal neutron dosemeter results obtained within the EVIDOS project.
AB  - Within the EC project EVIDOS ('Evaluation of Individual Dosimetry in Mixed
      Neutron and Photon Radiation Fields'), different types of active neutron personal
      dosemeters (and some passive ones) were tested in workplace fields at nuclear
      installations in Europe. The results of the measurements which have been
      performed up to now are summarised and compared to our currently best estimates
      of the personal dose equivalent Hp(10). Under- and over-readings by more than a
      factor of two for the same dosemeter in different workplace fields indicate that
      in most cases the use of field-specific correction factors is required.

PMID- 17449909
TI  - On the reassessment of doses in TL-dosimetry by measuring the residual dose.
AB  - Second readouts and the photo-transferred thermoluminscence (PTTL) method are
      sometimes used to reassess high doses. When using the common LiF:Mg,Ti, if the
      second readout is performed by a regular readout cycle of 13.3 s, its efficiency
      is low and the estimations cannot be obtained with acceptable accuracy for low
      doses in the 10-100 mSv range. By applying the PTTL method, the efficiency is
      much higher, but a high background is also present, deteriorating the quality of
      the reassessment. A simple and efficient method was studied, which consists of
      expanding the heating time to 30 s. Although the efficiency relative to a
      standard readout is improved by only a factor of 3, the low background enables to
      obtain results with the same uncertainty as the more complicated PTTL method. By
      applying region of integration discrimination, the errors can be further
      diminished.

PMID- 17449910
TI  - High background radiation areas: the case of Villar de la Yegua village (Spain).
AB  - The starting point of the Spanish experience in the study of High Background
      Radiation Areas is the development of a nationwide indoor radon survey carried
      out in 1988. This campaign, belonging to the first Spanish Radon Framework,
      consisted of approximately 2000 indoor radon measurements which represented a
      valuable basis to face rigorously the radon issue in Spain. Together but
      indepently from this survey, since 1991 the Spanish Nuclear Safety Council, the
      National Uranium Company and several Universities have developed the so-called
      MARNA project with the aim of estimating potential radon emission from external
      gamma dose rates, radium concentrations in soil and geological parameters. During
      the last decade, several regional surveys have also been conducted to determine
      exposure to natural sources of radiation in different highly populated background
      radiation areas. Among them, the surroundings of the village of Villar de la
      Yegua Town, located in the western province of Salamanca, is the most important
      area of Spain from a radiological point of view, with the highest indoor radon
      concentrations, of up to 15,000 Bq m(-3) being found there. Until now, the main
      result of the study in this area showed a geometric mean radon concentration of
      818 Bq m(-3), which is 18 times higher than the national average. In this
      article, the results of the last survey, carried out in Villar de la Yegua during
      2004 are summarised. A geometric mean radon concentration of 1356 Bq m(-3) was
      found. Dose estimation coming from radon inhalation is also shown.

PMID- 17449911
TI  - Monte Carlo based voxel phantoms for in vivo internal dosimetry.
AB  - The purpose of this communication is to describe briefly the computer programs
      developed to generate the MCNP input file corresponding to any segmented
      tomographic data and its application to the calibration procedures for in vivo
      internal dosimetry. The method has been applied to the determination of 241Am in
      bone by measurement in skull and knee using MCNP voxel models of a real human
      head and knee based on the tomographic Voxelman and Arms Down phantoms developed
      by Zubal et al. at Yale University.

PMID- 17449912
TI  - Both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin
      homeostasis and growth in human HeLa cells.
AB  - Sphingomyelin (SM) is a vital component of cellular membranes in organisms
      ranging from mammals to protozoa. Its production involves the transfer of
      phosphocholine from phosphatidylcholine to ceramide, yielding diacylglycerol in
      the process. The mammalian genome encodes two known SM synthase (SMS) isoforms,
      SMS1 and SMS2. However, the relative contributions of these enzymes to SM
      production in mammalian cells remained to be established. Here we show that SMS1
      and SMS2 are co-expressed in a variety of cell types and function as the key
      Golgi- and plasma membrane-associated SM synthases in human cervical carcinoma
      HeLa cells, respectively. RNA interference-mediated depletion of either SMS1 or
      SMS2 caused a substantial decrease in SM production levels, an accumulation of
      ceramides, and a block in cell growth. Although SMS-depleted cells displayed a
      reduced SM content, external addition of SM did not restore growth. These results
      indicate that the biological role of SM synthases goes beyond formation of SM.

PMID- 17449913
TI  - EphrinA1 activates a Src/focal adhesion kinase-mediated motility response leading
      to rho-dependent actino/myosin contractility.
AB  - Eph receptors and ephrin ligands are widely expressed in epithelial cells and
      mediate cell repulsive motility through heterotypic cell-cell interactions.
      Several Ephs, including EphA2, are greatly overexpressed in certain tumors, in
      correlation with poor prognosis and high vascularity in cancer tissues. The
      ability of several Eph receptors to regulate cell migration and invasion likely
      contribute to tumor progression and metastasis. We report here that in prostatic
      carcinoma cells ephrinA1 elicits a repulsive response that is executed through a
      Rho-dependent actino/myosin contractility activation, ultimately leading to
      retraction of the cell body. This appears to occur through assembly of an EphA2
      associated complex involving the two kinases Src and focal adhesion kinase (FAK).
      EphrinA1-mediated repulsion leads to the selective phosphorylation of Tyr-576/577
      of FAK, enhancing FAK kinase activity. The repulsive response elicited by
      ephrinA1 in prostatic carcinoma cells is mainly driven by a Rho-mediated
      phosphorylation of myosin light chain II, in which Src and FAK activation are
      required steps. Consequently, Src and FAK are upstream regulators of the overall
      response induced by ephrinA1/EphA2, instructing cells to retract the cell body
      and to move away, probably facilitating dissemination and tissue invasion of
      ephrin-sensitive carcinomas.

PMID- 17449914
TI  - Mechanism of dynamitin-mediated disruption of dynactin.
AB  - Dynamitin is a commonly used inhibitor of cytoplasmic dynein-based motility in
      living cells. Dynamitin does not inhibit dynein directly but instead acts by
      causing disassembly of dynactin, a multiprotein complex required for dynein-based
      movement. In dynactin, dynamitin is closely associated with the subunits
      p150(Glued) and p24, which together form the shoulder and projecting arm
      structures of the dynactin molecule. In this study, we explore the way in which
      exogenous dynamitin effects dynactin disruption. We find that pure, recombinant
      dynamitin is an elongated protein with a strong propensity for self-assembly.
      Titration experiments reveal that free dynamitin binds dynactin before it causes
      release of subunits. When dynamitin is added to dynactin at an equimolar ratio of
      exogenous dynamitin subunits to endogenous dynamitin subunits (1x= 4 mol of
      exogenous dynamitin per mole of dynactin), exogenous dynamitin exchanges with
      endogenous dynamitin, and partial release of p150(Glued) is observed. When added
      in vast excess (> or =25x; 100 mol of exogenous dynamitin per mole of dynactin),
      recombinant dynamitin causes complete release of both p150(Glued) subunits, two
      dynamitins and one p24, but not other dynactin subunits. Our data suggest that
      dynamitin mediates disruption of dynactin by binding to endogenous dynamitin
      subunits. This binding destabilizes the shoulder structure that links the
      p150(Glued) arm to the Arp1 filament and leads to subunit release.

PMID- 17449915
TI  - Applying observations from forensic science to understanding the development of
      pressure ulcers.
AB  - Autopsies and pathology findings can enhance understanding of processes that
      occur while a person is still alive. Hence, wound care clinicians from all
      disciplines can learn about pressure-related injury from necrosis research
      performed on decedents by forensic pathologists. The current system of pressure
      ulcer staging and assessment is unidimensional and contains many gaps, leading to
      variations and errors in the way pressure damage to tissues is classified and
      described. To provide a foundation for the development of a theoretical temporal
      framework, deep tissue injury research results, expert observations, and
      interpretations of clinical events from within the disciplines of wound care and
      forensic science - as well as research and observations documented in the
      vascular, plastic reconstructive, and general surgery literature - were reviewed.
      The results suggest that many similarities exist between forensic descriptions of
      tissue necrosis post mortem and pressure-related necrosis, that deep tissue
      injury can be detected within 24 hours of occurrence, and that the time between
      visible signs of deep tissue injury and their occurrence can be estimated,
      providing the foundation for a temporal framework. While research to validate
      this temporal framework for pressure-related deep tissue injury is needed,
      clinicians can start applying these observations to help understand the
      circumstances surrounding the development of, and factors contributing to, the
      development of deep tissue injury. Clarification of timelines and improved
      understanding of deep tissue injury risk factors are needed.

PMID- 17449916
TI  - Recurring and antimicrobial-resistant infections:considering the potential role
      of biofilms in clinical practice.
AB  - Micro-organisms commonly produce biofilm, a polymeric matrix that is adherent to
      inert or living substances and frequently forms on environmental surfaces,
      medical devices, and traumatized or compromised living and nonviable necrotic
      tissues such as wounds. The micro-organisms in a biofilm interact with each other
      and their environment. They are refractory to conventional therapy and resist
      conventional methods for culturing; their coordinated activities can lessen the
      effect of antimicrobials and the host's defenses. The multifactorial mechanism of
      resistance varies and depends, in part, on the strain of the micro-organism. A
      biofilm is dynamic and may shed bacteria or bacteria may be released by trauma,
      resulting in local or systemic infectious disease. Released bacteria lose their
      protection - they become responsive to appropriate levels of antimicrobials and
      may be cultured using conventional culturing methods. Micro-organisms in biofilms
      may remain dormant for weeks or years before causing local or systemic signs and
      symptoms of infection and are commonly responsible for recurring infections after
      repeated trials of antibiotics. Most biofilm infection-related research findings
      have not reached clinical practice yet. However, clinician knowledge about the
      development of and difficulties culturing micro-organisms in biofilms and their
      resistance to antibiotics and biocides may lead to improved clinical outcomes in
      soft tissue and bone infections and the treatment of wounds.

PMID- 17449917
TI  - Comparison of wound irrigation and tangential hydrodissection in bacterial
      clearance of contaminated wounds: results of a randomized, controlled clinical
      study.
AB  - Thorough irrigation of contaminated or infected traumatic and open surgical
      wounds is considered standard practice. High-power pulse lavage is frequently
      used to facilitate the removal of surface contaminants and bacteria but studies
      to compare the results of various irrigation techniques are limited. The purpose
      of this randomized, controlled clinical study was to compare the ability of a
      high-pressure parallel waterjet (pressure range 5,025 to 7,360 psi) to pulse
      lavage (pressure 40 psi) in reducing wound bacterial counts. The higher velocity
      instrument utilizes a waterjet oriented parallel to the surface of the wound and
      can be used to cut and remove necrotic tissues. After obtaining informed consent,
      21 patients who presented with open surgical and traumatic wounds were randomly
      assigned to high-pressure parallel waterjet (n = 12) or pulse lavage (n = 9). Pre
      and post irrigation tissue culture results showed an average decrease in
      absolute bacterial counts of 90.8% in the high-pressure parallel waterjet and
      86.9% in the pulse lavage group. The difference between the two treatment groups
      was not statistically significant. The results of this study confirm that
      cleansing contaminated or infected acute wounds using high pressure (at least 15
      psi) reduces wound bacterial counts. Studies to compare the clinical outcomes of
      various irrigation techniques and pressure ranges are warranted and the potential
      benefit of selective debridement using the high-pressure parallel waterjet should
      be investigated.

PMID- 17449918
TI  - Micronized, particulate dermal matrix to manage a non-healing pressure ulcer with
      undermined wound edges: a case report.
AB  - Pressure ulcers with undermined edges are generally hard to treat and may require
      surgical debridement and flap coverage. A woman with a 5-month history of a non
      healing, undermined, sacro-coccygeal pressure ulcer presented for care at the
      author's wound care center. Because traditional wound care had failed and
      surgical debridement and repair was contraindicated due to her overall poor
      general health and malnutrition, an injectable dermal filler was applied inside
      the wound. The matrix filler was covered with secondary and tertiary dressings
      and the wound healed after 8 weeks with no adverse effects or infection. The
      results of this and previously published case studies suggest that injectable
      dermal matrix may be a viable option for non-surgical treatment of difficult-to
      heal pressure ulcers with undermining. Additional safety, efficacy, and cost
      effectiveness studies seem warranted.

PMID- 17449919
TI  - Increased chromosome instability and accumulation of DNA double-strand breaks in
      Werner syndrome cells.
AB  - Werner syndrome (WS) is a premature aging syndrome caused by mutations of the WRN
      gene. Here, we demonstrate that a strain of WS fibroblast cells shows abnormal
      karyotypes characterized by several complex translocations and 50-fold more
      frequency of abnormal metaphases including dicentric chromosomes without
      fragments than normal cells when examined at a similar culture stage. Further,
      telomere fluorescence in situ hybridization indicates that the abnormal signals,
      extra telomere signal and loss of telomere signal, emerge two- to three-fold more
      frequently in WS cells than in normal cells. Taken together, these results
      indicate that chromosome instability including dysfunction of telomere
      maintenance is more prominent in WS cells than in normal cells. In addition, the
      accumulation of DNA double-strand breaks (DSBs) at the G(1) phase, including
      those at telomeres, detected by phosphorylated ATM (ataxia telangiectasia
      mutated) foci is accelerated in WS cells even at a low senescence level. The
      increased accumulation of DSBs in WS cells is reduced in the presence of anti
      oxidative agents, suggesting that enhanced oxidative stress in WS cells is
      involved in accelerated accumulation of DSBs. These results indicate that WS
      cells are prone to accumulate DSBs spontaneously due to a defect of WRN, which
      leads to increased chromosome instability that could activate checkpoints,
      resulting in accelerated senescence.

PMID- 17449920
TI  - Marked suppression of ghrelin concentration by insulin in Prader-willi syndrome.
AB  - The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome
      (PWS) and modulated by insulin. It was hypothesized that insulin might have a
      more pronounced effect on reducing plasma ghrelin in PWS patients, which would
      influence appetite. This study investigated the degree of ghrelin suppression
      using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal
      children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level
      decreased from a basal value of 0.86+/-0.15 to 0.58+/-0.12 ng/mL in the controls,
      and from 2.38+/-0.76 to 1.12+/-0.29 ng/mL in children with PWS (p=0.011). The
      area under the curve below the baseline level over the 90 min insulin infusion
      was larger in children with PWS than in controls (-92.82+/-44.4 vs. -10.41+/-2.87
      ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion
      rate at steady state was similar in the two groups (p=0.088). The decrease in the
      ghrelin levels in response to insulin was more pronounced in the children with
      PWS than in the controls. However, the level of ghrelin was always higher in the
      children with PWS during the clamp study. This suggests that even though insulin
      sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin
      levels is characteristic of PWS.

PMID- 17449921
TI  - Time sequence of airway remodeling in a mouse model of chronic asthma: the
      relation with airway hyperresponsiveness.
AB  - During the course of establishing an animal model of chronic asthma, we tried to
      elucidate the time sequence of airway hyperresponsiveness (AHR), airway
      inflammation, airway remodeling, and associated cytokines. Seven-week-old female
      BALB/c mice were studied as a chronic asthma model using ovalbumin (OVA). After
      sensitization, mice were exposed twice weekly to aerosolized OVA, and were
      divided into three groups depending on the duration of 4 weeks, 8 weeks, and 12
      weeks. At each time point, airway responsiveness, inflammatory cells, cytokines
      in bronchoalveolar lavage fluids (BALF), serum OVA-specific IgE, IgG1, IgG2a, and
      histological examination were carried out. AHR to methacholine, increased levels
      of OVA-specific IgG1 and IgG2a, and goblet cell hyperplasia were continuously
      sustained at each time point of weeks. In contrast, we observed a time-dependent
      decrease in serum OVA-specific IgE, BALF eosinophils, BALF cytokines such as IL
      13, transforming growth factor-beta1, and a time-dependent increase in BALF
      promatrix metalloproteinase-9 and peribronchial fibrosis. In this OVA-induced
      chronic asthma model, we observed airway remodelings as well as various cytokines
      and inflammatory cells being involved in different time-dependent manners.
      However, increased airway fibrosis did not directly correlate with a further
      increase in airway hyperresponsiveness.

PMID- 17449922
TI  - A useful predictor of early atherosclerosis in obese children: serum high
      sensitivity C-reactive protein.
AB  - Childhood obesity seems to contribute to the development of vascular inflammation
      and the progression of arterial wall changes. High-sensitivity C-reactive protein
      (hs-CRP) has recently emerged as a useful biomarker for vascular inflammation
      associated with atherosclerosis. The objectives of this study were to evaluate
      the association of the serum hs-CRP level with ultrasonic findings of early
      atherosclerosis, carotid intima-media wall thickness (IMT) and brachial flow
      mediated dilation (FMD), in obese children. Thirty eight obese children and 45
      sex/age-matched healthy control children were recruited. Serum CRP levels were
      measured by the high-sensitive latex turbidimetric immunoassay, and we measured
      carotid IMT and brachial FMD using high-resolution B-mode ultrasonography. Obese
      children had significantly higher hs-CRP levels (1.40+/-0.74 mg/L vs. 0.55+/-0.49
      mg/L, p<0.01), as well as increased IMT (0.52+/-0.09 mm vs. 0.41+/-0.07 mm,
      p<0.01) and impaired FMD (7.35+/-7.78% vs. 20.34+/-16.81%, p<0.01) compared to
      healthy controls. Serum hs-CRP correlated positively with IMT (r=0.413, p<0.05)
      and inversely with FMD (r=-0.350, p<0.05) in the obesity group. Measurement of
      the serum hs-CRP level is a simple, cheap, and highly reproducible assay and
      correlates with IMT and FMD in obese children. Thus, it would be a useful marker
      for evaluating and estimating the degree of atherosclerosis in children.

PMID- 17449923
TI  - Effect of cosensitization with buckwheat flour extract on the production of house
      dust mite-specific IgE.
AB  - There are studies reporting food sensitization in infancy increases the risk of
      sensitization to inhalants later in life. We performed a study to evaluate
      whether cosensitization with buckwheat (BW) has an effect on the production of
      house dust mite-IgE. C3H/HeJ mice (4 weeks, female) were sensitized with house
      dust mite (HDM)/Al (OH)(3), intraperitoneally on day 0, followed by 4 intranasal
      sensitizations (on days 14, 15, 16, and 21). Group 1 was cosensitized
      intragastrically with BW/cholera toxin (CT) (on days 0, 1, 2, 7, and 18) during
      sensitization with HDM, group 2 was cosensitized intragastrically with CT only
      (on days 0, 1, 2, 7, and 18), and group 3 was used as controls. HDM- and BW-IgE
      and antigen-specific T-cell proliferation and cytokine production were evaluated.
      In Group 1, BW-IgE levels were highest at week 4, and the HDM-IgE at week 3
      (98.45+/-64.37 ng/mL and 169.86+/-55.54 ng/mL, respectively). In Group 2, HDM-IgE
      levels reached a peak at week 3, remarkably higher (810.52+/-233.29 ng/mL)
      compared to those of Group 1 (169.86+/-55.54 ng/mL). The interleukin (IL)-4 and
      interferon (IFN)-beta in the HDM-stimulated culture supernatants of splenocytes
      were not significantly different among groups. We postulate that the
      cosensitization with BW may down-regulate the specific IgE response to HDM.

PMID- 17449924
TI  - Clonazepam treatment of pathologic childhood aerophagia with psychological
      stresses.
AB  - The treatment of pathologic aerophagia has rarely been discussed in the
      literature. In this retrospective study, the authors investigated the effects of
      clonazepam on the management of pathologic childhood aerophagia (PCA) with
      psychological stresses (PS), but not with mental retardation. Data from 22
      consecutive PCA patients with PS (aged 2 to 10 yr), who had been followed up for
      over 1 yr, were reviewed. On the basis of videolaryngoscopic views, the authors
      observed that the pathology of aerophagia was the result of reflex-induced
      swallowing with paroxysmal openings of the upper esophageal sphincter due to
      unknown factors and also observed that these reflex-induced openings were
      subsided after intravenous low dose benzodiazepine administration. Hence,
      clonazepam was administered to treat paroxysmal openings in these PCA patients
      with PS. Remission positivity was defined as symptom-free for a consecutive 1
      month within 6 months of treatment. The results of treatment in 22 PCA patients
      with PS were analyzed. A remission positive state was documented in 14.3% of PCA
      patients managed by reassurance, and in 66.7% of PCA patients treated with
      clonazepam (p=0.032). Thus, clonazepam may produce positive results in PCA with
      PS. Future studies by randomized and placebo-controlled trials are needed to
      confirm the favorable effect of clonazepam in PCA.

PMID- 17449925
TI  - Short-term efficacy of monthly pamidronate infusion in patients with osteogenesis
      imperfecta.
AB  - We evaluated the efficacy of a monthly infusion of pamidronate on the frequency
      of fractures, biochemical effects, and bone mineral density in children with
      osteogenesis imperfecta. Eleven patients from 0.9 to 13.8 yr of age were included
      in this study. The patients were administered pamidronate intravenously (30
      mg/m(2)) over a 4-hr period monthly for a period ranging from 6 to 37 months.
      Height and weight Z-scores did not change significantly. The frequency of
      fractures was decreased from 2.3+/-1.01 times per year before treatment to 0.6+/
      0.69 times per year during treatment. There were no long-term changes in
      biochemical markers during pamidronate therapy. The mean bone mineral density of
      the spine and femur increased significantly. Monthly intravenous pamidronate
      therapy decreased frequencies of fracture and increased bone mineral density
      without significant adverse events in Korean patients with osteogenesis
      imperfecta.

PMID- 17449926
TI  - Advanced criteria for clinicopathological diagnosis of food protein-induced
      proctocolitis.
AB  - The clinicopathological findings in previous studies concerning food protein
      induced proctocolitis (FPIPC) are quite diverse in terms of results and
      conclusions. The aim of this study was to suggest advanced clinicopathological
      diagnostic criteria that facilitate the early confirmation of FPIPC. Data of 38
      FPIPC patients, who had received sigmoidoscopy and biopsy, was analyzed.
      Microscopic findings were compared with observations of previous studies. Feeding
      at onset of bleeding was exclusively breast-fed (94.7%) and formula-fed or mixed
      fed (5.3%). Endoscopic abnormalities were observed in all patients; nodular
      hyperplasias with circumscribed and/or central pit-like erosions in 94.7% and
      erythema in 5.3%. Histopathological findings were; lymphoid aggregates in 94.7%,
      eosinophils in lamina propria of >or=60 cells/10 HPF in 97.4% and of >20
      cells/HPF in 63.2%, epithelial or muscularis mucosa eosinophil infiltration in
      97.4%, and crypt abscess in 2.6%. The majority of FPIPC patients are exclusively
      breast-fed and nodular hyperplasias with erosions may be a disease specific
      endoscopic finding. Histologic diagnosis of FPIPC is compatible with eosinophils
      in the lamina propria of >or=60 cells/10 high power fields; however, >20
      cells/HPF is not an appropriate diagnostic criterion.

PMID- 17449927
TI  - Emerging need for vaccination against hepatitis A virus in patients with chronic
      liver disease in Korea.
AB  - Vaccination against hepatitis A virus (HAV) is recommended for patients with
      chronic liver disease (CLD), but this has been deemed unnecessary in Korea since
      the immunity against HAV was almost universal in adults. However, this practice
      has never been reevaluated with respect to the changing incidence of adult acute
      hepatitis A. We retrospectively reviewed the medical records of 278 patients with
      acute hepatitis A diagnosed from January 1995 to November 2005 and prospectively
      tested 419 consecutive CLD patients from July to December 2005 for the presence
      of IgG anti-HAV. The number of patients with acute hepatitis A has markedly
      increased recently, and the proportion of adult patients older than 30 yr has
      been growing from 15.2% during 1995-1999, to 28.4% during 2000-2005 (p=0.019).
      Among 419 CLD patients, the seroprevalences of IgG anti-HAV were 23.1% for those
      between 26 and 30 yr, 64% between 31 and 35 yr, and 85.0% between 36 and 40 yr.
      These data demonstrate that immunity against HAV is no more universal in adult
      and substantial proportion of adult CLD patients are now at risk of HAV infection
      in Korea. Therefore, further study on seeking proper strategy of active
      immunization against HAV is warranted in these populations.

PMID- 17449928
TI  - Perioperative risk of hip arthroplasty in patients with cirrhotic liver disease.
AB  - We retrospectively reviewed the complete medical records of 30 patients with a
      diagnosis of liver cirrhosis who had undergone hip arthroplasty at three academic
      institutions between October 1994 and May 2001. There were 26 males and 4 females
      with a mean age of 60 yr at index operation. Surgical procedures included 17
      primary total hip arthroplasties (THA), 8 bipolar hemiarthroplasties, and 5
      revision THAs. According to the Child-Pugh scoring system, 19 cirrhotic patients
      were categorized as class A, 9 as class B, and 2 as class C. Eight (26.7%) of the
      30 patients had one or more perioperative complications. Of these, wound
      infection was the most common, with a rate of 10% (3 of 30 hips). Other
      perioperative complications included surgical site bleeding, coagulopathy,
      encephalopathy, gastrointestinal bleeding, pneumonia, and arrhythmia. Death
      occurred in 2 (6.7%) of the 30 patients; both were Child-Pugh's C cirrhotics. A
      higher Child-Pugh score (p=0.0001) and a high level of creatinine (p=0.0499) were
      associated with significantly increased perioperative complications or death. Our
      findings suggest that surgeons should be vigilant about perioperative
      complications in patients with advanced cirrhotic liver disease who undergo hip
      arthroplasty, albeit the mortality rates are relatively low in less severe
      cirrhotics.

PMID- 17449929
TI  - Allogeneic stem cell transplantation for patients with advanced hematological
      malignancies: comparison of fludarabine-based reduced intensity conditioning
      versus myeloablative conditioning.
AB  - We compared the outcomes of allogeneic hematopoietic stem cell transplantation
      using reduced intensity and myeloablative conditioning for the treatment of
      patients with advanced hematological malignancies. A total of 75 adult patients
      received transplants from human leukocyte antigen-matched donors, coupled with
      either reduced intensity (n=40; fludarabine/melphalan, 28;
      fludarabine/cyclophosphamide, 12) or myeloablative conditioning (n=35,
      busufan/cyclophosphamide). The patients receiving reduced intensity conditioning
      were elderly, or exhibited contraindications for myeloablative conditioning.
      Neutrophil and platelet engraftment occurred more rapidly in the reduced
      intensity group (median, 9 days vs. 18 days in the myeloablative group, p<0.0001;
      median 12 days vs. 22 days in the myeloablative group, p=0.0001, respectively).
      Acute graft-versus-host disease (>or=grade II) occurred at comparable frequencies
      in both groups, while the incidence of hepatic veno-occlusive disease was lower
      in the reduced intensity group (3% vs. 20% in the myeloablative group, p=0.02).
      The overall 1-yr survival rates of the reduced intensity and myeloablative group
      patients were 44% and 15%, respectively (p=0.16). The results of present study
      indicate that patients with advanced hematological malignancies, even the elderly
      and those with major organ dysfunctions, might benefit from reduced intensity
      transplantation.

PMID- 17449930
TI  - The increase in hepatic uncoupling by fenofibrate contributes to a decrease in
      adipose tissue in obese rats.
AB  - Fenofibrate is a drug that has been suggested to inhibit weight gain by
      increasing the catabolism of fatty acid in the hepatic mitochondria. We
      hypothesized that fenofibrate induces an increase in energy expenditure in the
      hepatic mitochondria, which results in the reduction of adipose tissue. In this
      study we measured hepatic uncoupling protein (UCP)-2, -3, core temperatures and
      abdominal fat composition with MRI in Otsuka Long-Evans Tokushima Fatty rats. The
      fenofibrate group (n=7) was fed fenofibrate (320 mg/kg) mixed chow. The control
      group (n=7) was fed chow only. The body weight (531.6+/-7.6 g) of the fenofibrate
      group was significantly lower than that (744.3+/-14.9 g) of the control group
      (p<0.005). The areas of visceral and subcutaneous fat in the fenofibrate group
      (11.0+/-0.9 cm(2), 4.2+/-0.3 cm(2)) were significantly less than those in the
      control group (21.0+/-0.7 cm(2), 7.4+/-0.4 cm(2)) (p=0.046, respectively). The
      esophageal and rectal temperatures of the fenofibrate group (37.7+/-0.1 degrees
      C, 33.1+/-0.2 degrees C) were significantly higher than those of the control
      group (37.3+/-0.1 degrees C, 32.2+/-0.1 degrees C) (p=0.025, p=0.005). There was
      de novo expression of UCP-3 in the liver of the fenofibrate group. These data
      suggest that increased energy dissipation, via hepatic UCP-3 by fenofibrate,
      contribute to decreased weight gain in obese rats.

PMID- 17449931
TI  - Cotransplantation of cord blood hematopoietic stem cells and culture-expanded and
      GM-CSF-/SCF-transfected mesenchymal stem cells in SCID mice.
AB  - Mesenchymal stem cells (MSC) are multipotent in nature and believed to facilitate
      the engraftment of hematopoietic stem cells (HSC) when transplanted
      simultaneously in animal studies and even in human trials. In this study, we
      transfected culture-expanded MSC with granulocyte macrophage-colony stimulating
      factor (GMCSF) and stem cell factor (SCF) cytokine genes and then cotransplanted
      with mononuclear cells (MNC) to further promote HSC engraftment. MNC were
      harvested from cord blood and seeded in long-term culture for ex vivo MSC
      expansion. A total of 1 x 10(7) MNC plus MSC/microL were introduced to the tail
      vein of nonobese diabetic/severe combined immunodeficiency mice. After 6-8 weeks
      later, homing and engraftment of human cells were determined by flow cytometry
      and fluorescence in situ hybridization studies. The total nucleated cell count
      and the engraftment of CD45+/CD34+ cells and XX or XY positive human cells were
      significantly increased in cotransplanted mice and even higher with the cytokine
      gene-transfected MSC (GM-CSF>SCF, p<0.05) than in transplantation of MNC alone.
      These results suggest that MSC transfected with hematopoietic growth factor genes
      are capable of enhancing the hematopoietic engraftment. Delivering genes involved
      in homing and cell adhesions, CXCR4 or VLA, would further increase the efficiency
      of stem cell transplantation in the future.

PMID- 17449932
TI  - Relationship between twin-to-twin delivery interval and umbilical artery acid
      base status in the second twin.
AB  - The purpose of this study was to determine the effect of twin-to-twin delivery
      interval on umbilical artery acid-base status of the second twin at birth. This
      was a retrospective cohort study of all live-born twins with measured acid-base
      status in umbilical arterial blood who were delivered after 34 weeks' gestation
      from June 2003 to February 2006. Twins with any maternal or fetal complications
      were excluded. Subjects were divided into two groups based on the mode of
      delivery of the first twin: normal cephalic vaginal deliveries (n=40) or cesarean
      deliveries (n=67). The inter-twin differences in umbilical arterial blood pH,
      PCO(2), PO(2), and base excess in twin newborns born vaginally were significantly
      greater than the corresponding differences in those born by cesarean section. A
      significant positive correlation was found between twin-to-twin delivery interval
      and inter-twin difference in umbilical arterial blood pH in twin newborns born
      vaginally. The umbilical arterial blood pH of the second twin was less than 7.0
      in 14% (2/14) in cases delivered more than 20 min after the first twin. The
      umbilical arterial blood gas status of the second twin worsened with increasing
      twin-to-twin delivery interval, and pathologic fetal acidemia (pH<7.0) might
      develop in the second twin when the twin-to-twin delivery interval was greater
      than 20 min.

PMID- 17449933
TI  - A comparative study of pericostal and submuscular bar fixation technique in the
      Nuss procedure.
AB  - We evaluated the safety and stability of the less-invasive submuscular bar
      fixation method in the Nuss procedure. One hundred and thirteen patients
      undergoing the Nuss procedure were divided into three groups according to the bar
      fixation technique employed. Group 1 consisted of 25 patients who had undergone
      bilateral pericostal bar fixation, group 2 consisted of 39 patients with
      unilateral pericostal one, and group 3 included 49 patients with bilateral
      submuscular one. The patients' age ranged from 2 to 25 yr, with an average of
      7.2+/-5.67 yr. Bar dislocation occurred in 1 patient (4%) in Group 1, 2 patients
      (5.1%) in Group 2, and 1 patient (2.0%) in Group 3 (p=0.46). Hemothorax was noted
      in 2 patients (8%) in Group 1, 2 (5.1%) in Group 2, and none (0%) in Group 3
      (Group 1 vs. Group 3, p=0.028). The mean operation time was shorter in Group 3
      than Group 1 (50.1+/-21.00 in Group 3 vs. 67.2+/-33.07 min in Group 1, p=0.041).
      The submuscular bar fixation results in a decrease in technique-related
      complications and operation time and is associated with favorable results with
      regard to the prevention of bar dislodgement.

PMID- 17449934
TI  - Low molecular weight heparin treatment in pregnant women with a mechanical heart
      valve prosthesis.
AB  - No definitive recommendation is available concerning optimal antithrombotic
      therapy in pregnant women with a mechanical heart valve. The purpose of the
      current study was to evaluate the clinical results of nadroparin treatment with
      respect to pregnancy outcome and maternal complications. From 1997 to 2005, 31
      pregnancies were reviewed in 25 women. Nadroparin (7,500 U, twice daily) was used
      in 23 pregnancies between 6 and 12 weeks of gestation and close-to-term only, and
      coumarin derivatives were used with aspirin at other times. Eight pregnant women
      treated with coumarin derivatives throughout pregnancy were compared to evaluate
      the safety and efficacy of nadroparin. No maternal death or bleeding complication
      occurred in either of the two groups, and frequencies of maternal thromboembolism
      including valve thrombosis (8.7% vs. 12.5%, p>0.05) were similar. However, the
      frequencies of live born (91.3% vs. 50%, p=0.01) and healthy babies (90.4% vs.
      25%, p<0.01) were significantly higher, and the fetal loss rate was significantly
      lower (8.7% vs. 50%, p=0.01) in the nadroparin-treated group. Regarding the
      efficacy and safety of antithrombotic treatment in pregnant women with prosthetic
      heart valves, nadroparin treatment during the first trimester is an acceptable
      regimen and produces better results than coumarin derivatives.

PMID- 17449935
TI  - Modified acellularization for successful vascular xenotransplantation.
AB  - The purpose of this study was to estimate the possibilities of an acellular
      matrix using a modified acellularization protocol, which circumvents
      immunological, microbiological, and physiological barriers. We treated porcine
      subclavian arteries with various reagents to construct acellular grafts.
      Afterwards, these grafts were interposed in a mongrel dogs' abdominal aorta. Six
      dogs underwent interposition with fresh porcine grafts (control group), and seven
      had interposed acellular grafts (acellular group). The control and acellular
      group dogs were sacrificed at 1, 3, 5 (n=2 in each group) and 12 months (n=1 in
      acellular group) after the operation. Histopathological examinations were then
      performed, to assess the degree to which re-endothelialization, inflammation,
      thrombus formation, and calcification occurred. The entire acellular group, but
      none of the control group, exhibited re-endothelialization. The degrees to which
      inflammation, thrombosis, and calcification occurred were found to be lower in
      the acellular group. We also discovered many smooth muscle cells in the medial
      layer of the xenograft that had been implanted in the dog sacrificed 12 months
      after the operation. These results suggest that the construction of xenografts
      using our modified acellularization protocol may offer acceptable outcomes as a
      vascular xenograft.

PMID- 17449936
TI  - Clinical outcome of urgent coronary artery bypass grafting.
AB  - Urgent coronary artery bypass grafting (CABG) has a higher mortality rate than
      elective CABG. The purpose of this study was to evaluate the clinical outcome of
      urgent CABG. From July 1992 to May 2005, 104 patients underwent urgent CABG. All
      patients required an urgent surgical revascularization within 24 hr of diagnostic
      coronary angiography. In-hospital mortality after urgent CABG was 17.3% (18/104).
      We compared preoperative characteristics and postoperative clinical outcomes
      between the survival group (n=86) and the mortality group (n=18). The mean age
      was 61.7 yr (range, 35-83). The most common cause of mortality was low cardiac
      output. The independent preoperative risk factors of mortality included advanced
      age (>70 yr) (OR=3.998, p=0.046), preoperative shock status (OR=6.542, p=0.011),
      and low ejection fraction (<40%) (OR=4.492, p=0.034). Other risk factors of
      mortality included prolonged cardiopulmonary bypass time, prolonged ventilator
      use, and extended intensive care unit stay. The 10-yr actuarial survival rate was
      61%. Although the operative mortality rate was high after urgent CABG, a
      favorable long-term clinical outcome can be expected if the patients survive.

PMID- 17449937
TI  - Role of complement regulatory proteins in the survival of murine allo
      transplanted Sertoli cells.
AB  - Sertoli cells (SC) are known to contain immunoprotective properties, which allow
      them to survive as allografts without the use of immunosuppressive drugs.
      Experiments were designed to determine which factors are related to prolonged
      survival of allogeneic SC. Balb/c derived Sertoli (TM4) and colon cancer (CT-26)
      cell lines were implanted beneath the kidney capsule of non-immunosuppressed
      C57BL/6 mice and compared their survival as allografts. Compared to TM4 graft,
      which survived more than 7 days after transplantation, CT-26 showed massive
      infiltration of polymorphonuclear cells, necrosis and enlargement of draining
      lymph nodes. Cultured cell lines showed no differences in their expression
      patterns of FasL, TGF beta1, clusterin and two complement regulatory proteins
      (CRP, i.e., membrane cofactor protein, MCP; decay accelerating factor, DAF), but
      protectin (CD59), another member of CRP was expressed only on TM4. These results
      suggest that CD59 and unknown factors may contribute to the prolonged survival of
      SC in non-immunoprivileged sites.

PMID- 17449939
TI  - Autocrine extracellular signal-regulated kinase activation in normal human
      keratinocytes is not interrupted by calcium triggering and is involved in the
      control of cell cycle at the early stage of calcium-induced differentiation.
AB  - Normal human epidermal keratinocytes (NHEK) respond to the autocrine activated
      extracellular signal-regulated kinase (ERK) signaling pathway, which contributes
      to the survival of keratinocytes. However, during the condition of calcium
      induced differentiation, how the autocrine ERK signaling is regulated and
      affected is poorly understood. The purpose of this study was to understand and to
      obtain clues to the possible function of the autocrine ERK activation during the
      calcium-induced differentiation of NHEK. We demonstrated that the autocrine
      activated ERK was not interrupted by calcium triggering and that it was sustained
      for at least one day after changing the medium. We also found that the autocrine
      ERK activation was associated with the expression of cyclin D1 and the cell cycle
      regulation at the early stage of calcium triggering by treating the cells with
      the mitogen-activated protein kinase inhibitor PD98059. However, the PD98059
      treatment did not have a significant influence on the expression of involucrin
      and loricrin. In addition, we demonstrated that autocrine ERK activation was
      associated with protein kinase C and p38MAPK signaling. We suggest that the
      activation of autocrine ERK is not interrupted by calcium triggering and it might
      participate in cell growth during the early stage of calcium-induced
      differentiation in NHEK.

PMID- 17449938
TI  - Promotive effect of minoxidil combined with all-trans retinoic acid (tretinoin)
      on human hair growth in vitro.
AB  - Minoxidil induces hair growth in male pattern baldness and prolongs the anagen
      phase. All-trans retinoic acid (ATRA) has been reported to act synergistically
      with minoxidil in vivo: they can enhance more dense hair regrowth than either
      compound alone. We evaluated the effect of minoxidil combined with ATRA on hair
      growth in vitro. The effect of co-treatment of minoxidil and ATRA on hair growth
      was studied in hair follicle organ culture. In cultured human dermal papilla
      cells (DPCs) and normal human epidermal keratinocytes, the expressions of Erk,
      Akt, Bcl-2, Bax, P53 and P21 were evaluated by immunoblot analysis. Minoxidil
      plus ATRA additively promoted hair growth in vitro, compared with minoxidil
      alone. In addition, minoxidil plus ATRA elevated phosphorylated Erk,
      phosphorylated Akt and the ratio of Bcl-2/Bax, but decreased the expressions of
      P53 and P21 more effectively than by minoxidil alone. Our results suggest that
      minoxidil plus ATRA would additively enhance hair growth by mediating dual
      functions: 1) the prolongation of cell survival by activating the Erk and Akt
      signaling pathways, and 2) the prevention of apoptosis of DPCs and epithelial
      cells by increasing the ratio of Bcl-2/Bax and downregulating the expressions of
      P53 and P21.

PMID- 17449940
TI  - Sphingosine 1-phosphate triggers apoptotic signal for B16 melanoma cells via ERK
      and caspase activation.
AB  - The bioactive sphingolipid metabolite sphingosine 1-phosphate (S1P), recently was
      reported to induce apoptosis of some cancer cells and neurons, although it
      generally known to exert mitogenic and antiapoptotic effects. In this study, we
      investigated the effects of S1P on the cell growth, melanogenesis, and apoptosis
      of cultured B16 mouse melanoma cells. In results, S1P was found to induce
      apoptosis in B16 melanoma cells in a dose- and time-dependent manner, but exerted
      minimal effects on melanogenesis. Although receptors of sphingosine 1-phosphate
      (endothelial differentiation gene 1 [Edg]/S1P(1), Edg5/S1P(2), Edg3/S1P(3)) were
      expressed in B16 melanoma cells, they were shown not to be associated with S1P
      induced apoptosis. In addition, pertussis toxin did not block the apoptotic
      effects of S1P on B16 melanoma cells. S1P induced caspase-3 activation and the
      extracellular signal-regulated kinase (ERK) activation. Interestingly, the ERK
      pathway inhibitor, UO126, reversed the apoptotic effects of S1P on B16 melanoma
      cells. These results suggest that S1P induced apoptosis of B16 melanoma cells via
      an Edg receptor-independent, pertussis toxin-insensitive pathway, and appears to
      be associated with the ERK and caspase-3 activation.

PMID- 17449941
TI  - Claudin-7 is highly expressed in chromophobe renal cell carcinoma and renal
      oncocytoma.
AB  - Claudin-7 has recently been suggested to be a distal nephron marker. We tested
      the possibility that expression of claudin-7 could be used as a marker of renal
      tumors originating from the distal nephron. We examined the immunohistochemical
      expression of claudin-7 and parvalbumin in 239 renal tumors, including 179 clear
      cell renal cell carcinoma (RCC)s, 29 papillary RCCs, 20 chromophobe RCCs, and 11
      renal oncocytomas. In addition, the methylation specific-PCR (MSP) of claudin-7
      was performed. Claudin-7 and parvalbumin immunostains were positive in 3.4%, 7.8%
      of clear cell RCCs, 34.5%, 31.0% of papillary RCCs, 95.0%, 80.0% of chromophobe
      RCCs, and 72.7%, 81.8% of renal oncocytomas, respectively. The sensitivity and
      specificity of claudin-7 in diagnosing chromophobe RCC among subtypes of RCC were
      95.0% and 92.3%. Those of parvalbumin were 80.0% and 88.9%. The expression
      pattern of claudin-7 was mostly diffuse in chromophobe RCC and was either focal
      or diffuse in oncocytoma. All of the cases examined in the MSP revealed the
      presence of unmethylated promoter of claudin-7 without regard to claudin-7
      immunoreactivity. Hypermethylation of the promoter might not be the underlying
      mechanism for loss of its expression in RCC. Claudin-7 can be used as a useful
      diagnostic marker in diagnosing chromophobe RCC and oncocytoma.

PMID- 17449942
TI  - Methylation profiles of CpG island loci in major types of human cancers.
AB  - Several reports have described aberrant methylation in various types of human
      cancers. However, the interpretation of methylation frequency in various human
      cancers has some limitations because of the different materials and methods used
      for methylation analysis. To gain an insight into the role of DNA
      hypermethylation in human cancers and allow direct comparison of tissue specific
      methylation, we generated methylation profiles in 328 human cancers, including 24
      breast, 48 colon, 61 stomach, 48 liver, 37 larynx, 24 lung, 40 prostate, and 46
      uterine cervical cancer samples by analyzing CpG island hypermethylation of 13
      genes using methylation-specific PCR. The mean numbers of methylated genes were
      6.5, 4.4, 3.6, 3.4, 3.1, 3.1, 3.1, and 2.1 in gastric, liver, prostate, larynx,
      colon, lung, uterine cervix, and in breast cancer samples, respectively. The
      number of genes that were methylated at a frequency of more than 40% in each
      tumor type ranged from nine (stomach) to one (breast). Generally genes frequently
      methylated in a specific cancer type differed from those methylated in other
      cancer types. The findings indicate that aberrant CpG island hypermethylation is
      a frequent finding in human cancers of various tissue types, and each tissue type
      has its own distinct methylation pattern.

PMID- 17449943
TI  - Immunohistochemical analysis of non-small cell lung cancer: correlation with
      clinical parameters and prognosis.
AB  - Non-small cell lung cancers (NSCLC) vary in their biologic behavior. Recurrence
      and tumor-related mortality may be attributable to molecular abnormalities in
      primary tumors. This study evaluated such immunophenotypes with regard to cell
      cycle regulation and proliferation, apoptosis, and angiogenesis, to determine
      their significance for patient outcome. Core biopsies from 219 patients with
      NSCLC were assembled on tissue microarrays, and the expressions of p16, p21, p27,
      cyclin B1, cyclin E, Ki-67, caspase-3, survivin, bcl-2, VEGF, and endostatin were
      evaluated by immunohistochemistry. Despite previously described prognostic
      relevance of some of the investigated molecules, many of those markers were not
      directly associated with recurrence or survival. However, there was a trend for
      p16 immunoreactivity to be associated with a good prognosis (57% vs. 42% in 5-yr
      survival) (p=0.071). bcl-2 expression was strongly correlated with a better
      outcome (65% vs. 45% in 5-yr survival) (p=0.029), and the hazard of death for bcl
      2 positive patients was 0.42 times of that for bcl-2 negative patients (p=0.047).
      A multivariate analysis with Cox proportional hazards model confirmed that the
      lymph node status (p=0.043) and stage (p=0.003) were other independent prognostic
      factors. Our results suggest that p16 and bcl-2 provide prognostic information
      independent of the TNM stage in NSCLC.

PMID- 17449944
TI  - Clinical efficacy of radiofrequency cervical zygapophyseal neurotomy in patients
      with chronic cervicogenic headache.
AB  - The purpose of the present study was to assess the clinical efficacy of
      radiofrequency (RF) cervical zygapophyseal joint neurotomy in patients with
      cervicogenic headache. A total of thirty consecutive patients suffering from
      chronic cervicogenic headaches for longer than 6 months and showing a pain relief
      by greater than 50% from diagnostic/prognostic blocks were included in the study.
      These patients were treated with RF neurotomy of the cervical zygapophyseal
      joints and were subsequently assessed at 1 week, 1 month, 6 months, and at 12
      months following the treatment. The results of this study showed that RF
      neurotomy of the cervical zygapophyseal joints significantly reduced the headache
      severity in 22 patients (73.3%) at 12 months after the treatment. In conclusion,
      RF cervical zygapophyseal joint neurotomy has shown to provide substantial pain
      relief in patients with chronic cervicogenic headache when carefully selected.

PMID- 17449945
TI  - One-year outcome evaluation after interspinous implantation for degenerative
      spinal stenosis with segmental instability.
AB  - The authors hypothesized that the placement of the interspinous implant would
      show a similar clinical outcome to the posterior lumbar interbody fusion (PLIF)
      in patients having spinal stenosis with mild segmental instability and that this
      method would be superior to PLIF without significantly affecting degeneration at
      the adjacent segments. Forty two adult patients having degenerative spinal
      stenosis with mild segmental instability who underwent implantation of Coflex
      (Spine motion, Germany) or PLIF at L4-5 between January 2000 and December 2003
      were consecutively selected and studied for one-year clinical outcome. At 12
      months after surgery, both groups showed a significant improvement in the visual
      analogue scale score and Oswestry disability index score for both lower extremity
      pain and low back pain. However, the range of motion at the upper adjacent
      segments (L3-4) increased significantly after surgery in the PLIF group, which
      was not manifested in the Coflex group during the follow-up. The authors assumed
      that interspinous implantation can be an alternative treatment for the spinal
      stenosis with segmental instability in selected conditions posing less stress on
      the superior adjacent level than PLIF.

PMID- 17449946
TI  - Triage method for out-of-hospital poisoned patients.
AB  - The aim of this study was to develop and evaluate a triage method to prevent
      unnecessary emergency department visits of out-of-hospital poisoned patients.
      From October 2003 to September 2004, the calls that lay persons gave to the Seoul
      Emergency Medical Information Center to seek advice on the out-of-hospital
      poisoned patients were enrolled. We designed a triage protocol that consisted of
      five factors and applied it to the patients. According to the medical outcomes,
      we classified the patients into two groups, the toxicity-positive and the
      toxicity-negative. We arranged the factors on the basis of the priority that was
      determined in order of the odds ratio of each factor for the toxicity-positive
      and made a flow chart as a triage method. Then we calculated a sensitivity,
      specificity, positive predictive value and negative predictive value of the
      method. We regarded the specificity as the ability of the method and the
      sensitivity as the safety. A total of 220 patients were enrolled in this study.
      The method showed a sensitivity, specificity, positive predictive value, and
      negative predictive value of 99.2%, 53.4%, 76.2%, and 97.9%, respectively. Our
      triage method prevented 53.4% of the unnecessary emergency department visits of
      out-of-hospital acutely poisoned patients, safely.

PMID- 17449947
TI  - The hemodynamic effects of insulin following overdosage with levobupivacaine or
      racemic bupivacaine in dogs.
AB  - Although levobupivacaine (LBUP) is less cardiotoxic than racemic bupivacaine
      (RBUP), the resuscitation from the LBUP-induced cardiovascular collapse (CVC) has
      not been easy as expected. Following the recent reports that proposed the
      resuscitative action of insulin for the RBUP-induced CVC, a controlled trial was
      performed to assess the feasibility of insulin for the LBUP-induced CVC. Fourteen
      dogs were randomly allocated into two groups: the RBUP and LBUP groups. Each
      group received continuous intravenous infusions of RBUP or LBUP until the mean
      arterial pressure (MAP) reached 40 mmHg. Then, an intravenous bolus of insulin (2
      U/kg) was administered. Both groups were successfully resuscitated. At CVC, a
      decrease of cardiac output and an increase of systemic vascular resistance were
      observed but to a lesser degree in the LBUP group (p<0.05). After insulin
      injection, the MAP further declined to under 40 mmHg for several minutes, which
      was more protracted in the LBUP group (p<0.05). The CVCs induced by LBUP or RBUP
      in anesthetized dogs could be successfully resuscitated by insulin. Compared with
      RBUP, however, the less degree of vasoconstriction by LBUP and the innate
      vasodilatory property of insulin yielded a delayed increment of MAP during the
      immediate resuscitation period in the LBUP-induced CVC.

PMID- 17449948
TI  - The effect of 2 Hz and 100 Hz electrical stimulation of acupoint on ankle sprain
      in rats.
AB  - The electrical stimulation of acupoint (ESA) releases several endogenous
      neuropeptides, which play important roles in management of pain and inflammation.
      ESA with low and high frequencies has been shown to release different
      neuropepides, suggesting its various therapeutic effects. Pain and edema are
      major problems for ankle sprain. However, there have been few reports on the
      effects of ESA for ankle sprain. We aimed to investigate that ESA can reduce pain
      and edema resulting from ankle sprain, and whether there is a difference in
      therapeutic effects between low and high frequency ESA. To induce ankle sprain in
      Sprague-Dawley rats, the ankle of right hindpaw was overextended in direction of
      simultaneous inversion and plantar flexion. Stepping force and edema in the paw
      of the sprained ankle were measured by electronic balance and plethysmometer,
      respectively. In both 2 and 100 Hz ESA groups, stepping force was increased
      significantly in similar degrees (p<0.05). Only 2 Hz ESA produced the significant
      rapid decrease in ankle edema. This study demonstrates that ESA of 2 Hz and 100
      Hz shows comparable analgesic effects, but only 2 Hz ESA can facilitate the
      reduction of edema caused by ankle sprain.

PMID- 17449949
TI  - The first Korean case of Beare-Stevenson syndrome with a Tyr375Cys mutation in
      the fibroblast growth factor receptor 2 gene.
AB  - Here we report the first case of a Korean infant with a cloverleaf-shaped
      craniosynostosis, in which the diagnosis of Beare-Stevenson syndrome was
      suspected upon observation of the typical morphological features. This infant
      exhibited craniofacial anomalies, ocular proptosis, cutis gyrata, acanthosis
      nigricans, prominent umbilical stump, furrowed palms and soles, hypospadia, and
      sacral skin tag coupled with dermal sinus tract. Brain magnetic resonance imaging
      revealed that the patient also had non-communicating hydrocephalus with Chiari
      malformation. This is the 8th report of Beare-Stevenson syndrome in the
      literature, which was confirmed by the detection of a Tyr375Cys mutation in the
      fibroblast growth factor receptor 2 (FGFR2) gene.

PMID- 17449950
TI  - A case of fetal congenital mesoblastic nephroma with oligohydramnios.
AB  - Although congenital renal tumors are rare, congenital mesoblastic nephroma (CMN)
      is the most common renal tumor in early infancy. It is non-metastatic, well
      differentiated, amenable to surgical removal, and carries a good prognosis.
      Polyhydramnios has been detected in most of the published cases of CMN. However,
      we experienced a rare case of fetal CMN associated with oligohydramnios. A 28-yr
      old woman at 34 weeks of gestation was referred to our hospital for
      oligohydramnios and a fetal abdominal mass. An ultrasonography revealed a huge,
      well-encapsulated mass arising from the right kidney. An emergency cesarean
      section was performed due to fetal distress. After birth, despite intensive
      neonatal care, the baby died because of renal failure, disseminated intravascular
      coagulopathy, pulmonary edema, together with other problems.

PMID- 17449951
TI  - Vaccine-associated paralytic poliomyelitis: a case report of flaccid monoparesis
      after oral polio vaccine.
AB  - This report describes a case of acute flaccid paralysis after administration of
      oral polio vaccine (OPV). A 4 month-old male patient with the decreased movement
      of left lower extremity for 1 month was transferred to the Department of
      Pediatrics. He received OPV with DTaP at 2 months of age. Flaccid paralysis was
      detected 4 weeks after OPV immunization. Attempts to isolate Sabin-like viruses
      in the two stool and CSF samples failed because those specimens were collected
      more than 2 month after the onset of paralysis. Hypotonic monoparesis (GIV/V),
      hypotonia and atrophy on the left lower extremity, and ipsilateral claw foot
      persisted for more than 18 months, while we followed him with rehabilitation
      therapy. This is the first case of officially approved, recipient vaccine
      associated paralytic poliomyelitis in Korea.

PMID- 17449952
TI  - Allergic bronchopulmonary aspergillosis coupled with broncholithiasis in a non
      asthmatic patient.
AB  - Allergic bronchopulmonary aspergillosis (ABPA), an asthmatic disease, is caused
      primarily by hypersensitivity to Aspergillus species. ABPA is rarely observed in
      the absence of asthma, which is, in fact, the principle criterion for its
      diagnosis. Here, we report the case of a 36-yr-old woman without a history of
      bronchial asthma, who manifested a localized pneumonic consolidation, coupled
      with broncholithiasis. Pathologic examinations of bronchoscopic biopsy specimens
      and resected surgical specimens revealed features typical of ABPA. This is a very
      rare case of ABPA coupled with broncholithiasis in a non-asthmatic individual.

PMID- 17449953
TI  - Primary alveolar soft part sarcoma of the lung.
AB  - Alveolar soft part sarcoma (ASPS) is a rare epithelial-like soft tissue sarcoma.
      The two main sites of its occurrence are the lower extremities in adults and the
      head and neck in children. Primary pulmonary involvement of this sarcoma, without
      evidence of soft tissue tumor elsewhere, is very exceptional. We present a case
      of primary ASPS of the lung in a 42-yr-old woman. A computed tomographic scan of
      the thorax demonstrated a well-circumscribed, solid tumor located in the right
      upper lobe. The mass was resected by right upper lobectomy. After 5 months, three
      metastatic lesions, involving lumbar vertebrae and occipital scalp, were found.
      Histologically, the tumor consisted of alveolar nests of large polygonal tumor
      cells, the cytoplasm of which frequently revealed periodic acid-Schiff-positive,
      diastase-resistant intracytoplasmic rod-like structures. On immunohistochemical
      staining, the tumor cells were positive only for vimentin and alpha-smooth muscle
      actin. Ultrastructural study using electron microscopy revealed characteristic
      electron-dense, rhomboid intracytoplasmic crystals.

PMID- 17449954
TI  - Primary polymorphous low-grade adenocarcinoma of lung treated by sleeve bronchial
      resection: a case report.
AB  - We report a surgical case of primary polymorphous low-grade adenocarcinoma (PLGA)
      of the minor salivary gland-type of the lung. A PLGA originating from the right
      upper lobar bronchial inlet was successfully treated by sleeve right upper
      lobectomy. PLGAs are thought to be indolent tumors that are preferentially
      localized to the palate, and they affect the minor salivary glands almost
      exclusively. Until now, two cases of distant metastases to the lung have been
      reported in the English literature. To the best of our knowledge, only one case
      of PLGA of minor salivary gland-type of the lung without evidence of a previous
      oropharyngeal primary tumor has been reported in the English literature. But the
      case was not a single lesion; it was bilateral tumors accompanied by tumors of
      the cervical lymph nodes. We report here the first case of a single primary PLGA
      of the minor salivary gland-type of the lung, which was successfully treated by
      sleeve bronchial resection of right upper lobe.

PMID- 17449955
TI  - Spontaneous bacterial peritonitis due to Ochrobactrum anthropi: a case report.
AB  - We report a case of spontaneous bacterial peritonitis from Ochrobactrum anthropi.
      O. anthropi is recognized as an emerging pathogen in immunocompromised patients.
      In contrast to most previously described cases, the patient reported here had no
      indwelling catheter. To our knowledge, no case of O. anthropi spontaneous
      bacterial peritonitis has been reported in the medical literature until now.

PMID- 17449956
TI  - Eikenella corrodens cervical spinal epidural abscess induced by a fish bone.
AB  - Cervical spinal epidural abscess, caused by fish bone injury and a secondary
      infection by Eikenella corrodens which is part of the normal flora, has not been
      reported. A 72-yr-old man came to the hospital with pain in his posterior neck
      and both shoulders for 2 months. He also was experiencing weakness on his right
      side for 3 days. A fish bone had been stuck in his throat for about 2 months.
      Neurological examination revealed right hemiparesis, hypesthesia on the left
      extremities and neck stiffness. Laboratory findings showed an elevated ESR/CRP
      and leukocytosis, and magnetic resonance imaging revealed a retropharyngeal
      abscess and cervical myelitis. The patient was treated with emergency surgical
      decompression and antibiotics. A fish bone was removed from the C3-C4
      intervertebral disc space. In the culture of chocolate blood agar and 5% sheep
      blood agar plate, E. corrodens was detected as a causative organism.

PMID- 17449957
TI  - Activated charcoal suppresses breeding of the house dust mite, Dermatophagoides
      pteronyssinus, in culture.
AB  - House dust mite sensitized asthmatics are advised to practice allergen avoidance.
      Charcoal pillows are used in Korea with unsubstantiated claims regarding their
      efficacy in alleviating asthma symptoms. We tested the effects of activated
      charcoal on breeding of house dust mites in culture. Twenty live adult house dust
      mites (Dermatophagoides pteronyssinus) were inoculated, 10 replicates, on culture
      media containing 0%, 1%, 3%, 5%, 10%, and 20% activated charcoal and incubated at
      25 degrees C and a relative humidity of 75%. After four weeks, the mean numbers
      of live house dust mites were 286, 176, 46, 16, 7, and 0 for the 0%, 1%, 3%, 5%,
      10%, and 20% charcoal-containing culture media, respectively. Thus, activated
      charcoal suppresses breeding of house dust mites and offers a new promising
      method for house dust mite control.

PMID- 17449958
TI  - Effect of inhaled iloprost during off-medication time in patients with pulmonary
      arterial hypertension.
AB  - BACKGROUND: Iloprost is a stable prostacyclin analogue that is associated with a
      longer duration of vasodilatation and has been approved for inhalative use with 6
      or 9 inhalations during the daytime and a night pause. It is not known if during
      the night pause rebound pulmonary hypertension occurs. The aim of this study was
      to assess the hemodynamics in iloprost-treated patients during the daytime and at
      night. METHODS: We enrolled 5 adult patients (aged 45 +/- 10 years) with
      idiopathic pulmonary arterial hypertension (IPAH) and chronic inhaled iloprost
      therapy for at least 12 months. Further medication remained unchanged during the
      study period. Hemodynamics were monitored by right heart catheterization.
      RESULTS: After 30-60 min of nebulized iloprost, mean pulmonary arterial pressures
      (PAP) decreased from 68 +/- 15 to 51 +/- 18 mm Hg (p = 0.004). After 6 h off
      medication sleeping time, mean PAP initially increased until 2 a.m. and decreased
      subsequently until wake-up time at 6 a.m. Mean PAP, cardiac index and pulmonary
      vascular resistance at night were not significantly different from the values
      during the day. CONCLUSIONS: In this study, patients with IPAH and chronic
      nebulized iloprost therapy did not reveal a rebound pulmonary hypertension during
      off-medication sleeping time.

PMID- 17449959
TI  - The effects of psychological intervention on atopic dermatitis. A systematic
      review and meta-analysis.
AB  - BACKGROUND: Psychological interventions may be valuable in atopic dermatitis. We
      systematically reviewed and carried out a meta-analysis of randomized controlled
      trials of psychological interventions. METHODS: Electronic searches and manual
      journal searches were carried out. Two coders independently coded study designs,
      participants, treatments and outcome characteristics of the studies meeting the
      selection criteria. RESULTS: Eight journal articles published between 1986 and
      2006 were included. Eight types of intervention were tested: aromatherapy,
      autogenic training, brief dynamic psychotherapy, cognitive-behavioral therapy,
      dermatological education and cognitive-behavioral therapy, habit reversal
      behavioral therapy, a stress management program, and structured educational
      programs. Effect sizes were computed as correlation coefficient (r), and random
      effects models were used in the analysis. For eczema severity, the average effect
      size for the 8 trials including 8 interventions was -0.367 [chi(2)(1) = 7.452, p
      = 0.006; 95% CI -0.579 to -0.108]. The average effect sizes on itching intensity
      (5 trials with 5 interventions) and scratching (5 trials with 4 interventions)
      were -0.805 [chi(2)(1) = 4.719, p = 0.030; 95% CI -0.971 to -0.108] and -0.620
      [chi(2)(1) = 24.24, p < 0.0001; 95% CI -0.767 to -0.410], respectively.
      CONCLUSIONS: Although the present meta-analysis revealed that psychological
      interventions had a significant ameliorating effect on eczema severity, itching
      intensity and scratching in atopic dermatitis patients, a definite conclusion
      about their effectiveness seems premature. Accordingly, future studies should
      involve more sophisticated methodologies, use established measures of outcome
      variables, adjust for possible confounders between the intervention and control
      groups, and provide sufficient data to calculate the effect sizes for future meta
      analyses.

PMID- 17449960
TI  - 'Look for the right mentor'. An interview with Prof. Manfred v. Singer.
AB  - Prof. Manfred V. Singer, a pioneer in the field of neuro-hormonal regulation of
      pancreatic exocrine secretion, is interviewed. He provided the first experimental
      proof of the existence of neural reflexes that control pancreatic functions.
      Here, Prof. Singer shares his life experience in pancreatic research and points
      out key aspects of a successful mentor-mentee relationship.

PMID- 17449961
TI  - Precursor lesions of pancreatic cancer: molecular pathology and clinical
      implications.
AB  - BACKGROUND: Pancreatic cancer is a lethal disease, with near uniform 5-year
      mortality rates. The key to improving survival of pancreatic cancer rests upon
      early detection of this neoplasm at a resectable, and hence potentially curable,
      stage. METHODS: We review the current state of the literature vis-a-vis the three
      common precursor lesions of pancreatic adenocarcinoma: pancreatic intraepithelial
      neoplasia, intraductal papillary mucinous neoplasm, and mucinous cystic neoplasm.
      We also discuss two clinical scenarios of emerging importance, namely
      asymptomatic pancreatic cysts ('pancreatic incidentalomas') and the significance
      of precursor lesions in familial pancreatic cancer kindreds. RESULTS: Pancreatic
      intraepithelial neoplasias are the microscopic precursor lesions of pancreatic
      adenocarcinomas, while intraductal papillary mucinous neoplasms and mucinous
      cystic neoplasms are macroscopic, cystic precursor lesions. All three noninvasive
      entities demonstrate a multistep morphologic and genetic progression that
      culminates in frank invasive adenocarcinoma. Despite these commonalities, each
      precursor lesion harbors a unique repertoire of clinicopathologic and genetic
      characteristics that has an impact on natural history and prognosis of these
      lesions. Due to improvements in radiological techniques, asymptomatic pancreatic
      cysts are being increasingly discovered in the general population; intraductal
      papillary mucinous neoplasms and mucinous cystic neoplasms are the most common
      underlying histology in resected incidentalomas of the pancreas. Pancreatic
      asymptomatic cysts present an enormous challenge in terms of accurate diagnosis
      and management stratification. Incorporating molecular signatures of cystic
      precursor lesions into the diagnostic algorithm will likely become a standard of
      care for asymptomatic pancreatic cysts. High-risk individuals from familial
      pancreatic cancer kindreds are another group of individuals where knowledge of
      precursor lesions has had a therapeutic impact; sensitive imaging technologies
      have enabled the identification and subsequent resection of pancreatic cancer
      precursors in these high-risk individuals, preventing the progression to invasive
      cancer. CONCLUSIONS: Precursor lesions of pancreatic adenocarcinomas represent a
      unique opportunity for diagnosis and intervention for a malignancy with near
      uniform lethality. Further studies on these precursors will enable the
      development of rational early detection and therapeutic strategies in order to
      ameliorate pancreatic cancer survival.

PMID- 17449962
TI  - Photodynamic therapy using verteporfin photosensitization in the pancreas and
      surrounding tissues in the Syrian golden hamster.
AB  - BACKGROUND/AIM: Photodynamic therapy (PDT) is a potential treatment for locally
      advanced pancreatic cancer. We aimed to assess the safety of interstitial PDT
      using verteporfin (benzoporphyrin derivative monoacid A - a novel photosensitizer
      with a short drug-light interval and limited cutaneous photosensitivity) in the
      Syrian golden hamster, and compare it to meso-tetrahydroxyphenylchlorin (mTHPC)
      which we have previously evaluated in preclinical and clinical studies. METHODS:
      Verteporfin (2 mg/kg) was administered at laparotomy by inferior vena caval
      injection (n = 57), with plasma levels quantified at 5, 15, 30, 60 and 240 min,
      and 24 h. 15 min after photosensitization, tissues (liver, pancreas, duodenum,
      colon, aorta) were illuminated with 690 nm red laser light (150 mW), at a range
      of light doses (1-100 J/cm(2)). The PDT effects on the targeted organ and
      adjacent structures were assessed at post-mortem on days 3 and 21, or at the time
      of death. RESULTS: The elimination half-life of verteporfin was 4-5 h. Light
      doses of 10, 25 and 50 J/cm(2) were safe in the hamster pancreas, liver and
      colon, respectively, and produced coagulative necrotic lesions of 3 (range 3-4),
      10 (9-10) and 7 (7-8) mm diameter. Collagen was resistant to damage and lesions
      healed mainly by regeneration of normal tissue. At higher light doses, necrosis
      extended to the edge of organs, sometimes causing sealed duodenal perforations as
      seen with mTHPC. CONCLUSION: The safety profile of verteporfin is very similar to
      mTHPC, with the advantages of a shorter drug-light interval and drug elimination
      time. Phase I clinical studies using this photosensitizer in pancreatic cancer
      should be feasible.

PMID- 17449963
TI  - Suppressive effect of herbal medicine saikokeishito on acinar cell apoptosis in
      rat spontaneous chronic pancreatitis.
AB  - BACKGROUND/AIMS: Chronic pancreatitis is characterized by acinar destruction and
      fibrosis. We previously reported that apoptosis is involved in acinar destruction
      in chronic pancreatitis in the WBN/Kob rat. This study aimed to elucidate the
      antiapoptotic effect of Saikokeishito (TJ-10). METHODS: Four-week-old male
      WBN/Kob rats were fed a special pellet diet (MB-3) with or without TJ-10 (80
      mg/100 g body weight) for 20 weeks. Pancreas was histopathologically examined
      every 4 weeks, and the expression of apoptosis-related factors such as Fas and
      Fas ligand (FasL) mRNA and protein was analyzed with RT-PCR, in situ
      hybridization and immunohistochemistry. Apoptosis was detected with a TUNEL
      method. RESULTS: In untreated WBN/Kob rats, chronic pancreatitis developed at 12
      weeks and progressed with marked acinar cell destruction at 16 weeks. The
      expression of Fas and FasL peaked at 12 and 20 weeks. An apoptotic index in
      acinar cells correlated to the expression of Fas and FasL mRNA. However, in the
      TJ-10-treated rats, the rate of pancreatic acinar cell destruction, the apoptotic
      index at 12-20 weeks, and the expression of Fas and FasL at 12 and 20 weeks
      decreased significantly compared to those in untreated rats. CONCLUSION: These
      results suggest that TJ-10 has a therapeutic effect on chronic pancreatitis by
      the suppression of acinar cell apoptosis via the Fas/FasL system.

PMID- 17449964
TI  - Pancreaticoduodenectomy for peri-ampullary neoplasia leads to specific
      micronutrient deficiencies.
AB  - BACKGROUND/AIMS: After pancreaticoduodenectomy (PD) patients may be deficient in
      essential micronutrients. This study was designed to determine if this is a
      consequence of surgery. METHODS: Long-term survivors (>6 months) of PD for peri
      ampullary neoplasia and healthy controls (patients' spouse/partner) were enrolled
      in the study. Specific clinical parameters were recorded, serum micronutrient
      levels were measured and subjects completed 7-day food diaries. RESULTS: Thirty
      seven patients were studied, 25 with paired controls. All were well nourished, as
      defined by body mass index and food diary analysis. Patients with paired controls
      were representative of all patients studied. Patients had raised transferrin
      (median 2.60 vs. 2.16 g/l, p = 0.001) and low ferritin levels (34.9 vs. 119.0
      g/l, p < 0.001) indicating relative iron deficiency. Patients also demonstrated
      lower levels of the anti-oxidants selenium (0.77 vs. 0.93 micromol/l, p < 0.001)
      and vitamin E (23.2 vs. 35.7 micromol/l, p < 0.001) with 57% of patients having
      frank selenium deficiencies. Patients had lower levels of vitamin D than controls
      (15.7 vs. 19.6 micromol/l, p = 0.001) and 30% of patients had a raised
      parathyroid hormone level, suggesting compensatory mechanisms operate to maintain
      normocalcaemia. CONCLUSIONS: Long-term survivors of PD are relatively deficient
      in several micronutrients compared to non-operated controls taking the same diet.
      We recommend that micronutrient status should be regularly checked in these
      patients and treated where necessary.

PMID- 17449965
TI  - Evaluation of topoisomerase IIa expression in pancreatic ductal adenocarcinoma: a
      pilot study using chromogenic in situ hybridization and immunohistochemistry on
      tissue microarrays.
AB  - BACKGROUND/AIMS: To co-evaluate topoisomerase IIa (Topo IIa) protein expression
      and gene status in pancreatic ductal adenocarcinoma, determining the potential
      prognostic impact of its alterations. METHODS: Using tissue microarrays, 50
      sporadic, primary pancreatic ductal adenocarcinomas were cored twice and re
      embedded into one paraffin block with a core diameter of 1 mm.
      Immunohistochemistry and chromogenic in situ hybridization were performed in
      serial tissue sections for the detection of protein expression levels, chromosome
      17 and Topo IIa gene status, respectively. Finally using a semi-automated image
      analysis system we evaluated the levels of protein expression. RESULTS: A
      significant proportion of the tumors showed Topo IIa overexpression (32/50 or
      64%). Gene amplification and deletion were detected in 9 and 4 cases,
      respectively, associated with protein overexpression. Aneuploidy regarding
      chromosome 17 was observed in 19/50 tumors and correlated with poor survival rate
      (Cox regression test: p = 0.001). Topo IIa protein expression was strongly
      correlated with stage (p = 0.021) and grade (p = 0.034). CONCLUSIONS: Topo IIa
      gene amplification correlates with protein overexpression, but not vice versa.
      This is a crucial observation for the application of targeted chemotherapies,
      such as anthracyclines, only in subgroups of patients, according to molecular
      deregulation criteria and not only to immunohistochemical results. Also,
      chromosome 17 and not Topo IIa gene instability can be used as a potential
      independent prognostic factor.

PMID- 17449966
TI  - Acute pancreatitis after embolization of liver tumors: frequency and associated
      risk factors.
AB  - INTRODUCTION: Acute pancreatitis (AP) is a rare complication after liver
      embolization (LE) of primary and secondary liver tumors (approximately 1.7%), but
      it has a significant morbidity and mortality potential if associated with other
      complications. It usually develops early within 24 h after the LE procedure.
      STUDY PURPOSE: To calculate the frequency of AP after LE in our institution and
      to analyze the factors involved in this procedure (anatomical features,
      embolization materials, cytostatic drugs, technical factors). MATERIALS AND
      METHODS: 118 LE (bland embolization and transarterial chemoembolization) were
      performed in our institution. The study group included 59 patients who met the
      following inclusion criteria: one or more LE events, with complete pre- and post
      interventional laboratory studies including: serum Ca(2+), creatinine, blood urea
      nitrogen, glucose, lactate dehydrogenase, aminotransferases, alkaline
      phosphatase, amylase, lipase, C-reactive protein, hematocrit and leukocytes. The
      diagnosis of AP was established according to the criteria of the Atlanta system
      of classification. For the statistical analysis the association between two
      response variables (e.g. AP after embolization and risk factor during the
      embolization, AP after embolization and volume of embolic material) was evaluated
      using Pearson's chi(2) test and Fisher's exact test. RESULTS: The calculated
      frequency of AP after LE in our series was 15.2%. Amylase and lipase were
      elevated up to 8.7 and 20.1 times, respectively, 24 h after LE. We observed a
      statistically significantly lower incidence of AP in those patients who received
      2 ml or less of embospheres compared with those with an embolization volume of >2
      ml (Pearson's chi(2) = 4.5000, Pr = 0.034, Fisher's exact test = 0.040). Although
      carboplatin was administered to 7 of 9 of the patients who developed AP after the
      embolization procedure, there was no statistical significance (Fisher's exact
      test = 0.197) for carboplatin as an AP risk factor when compared with all the
      patients who received this drug (n = 107). CONCLUSION: Although AP after LE seems
      to have a multifactorial etiology, both the toxicity of the antineoplastic drugs
      (carboplatin-related toxicity) as well as direct ischemic mechanisms (non-target
      embolization, reflux mechanisms) may be the most important causes of the
      inflammatory pancreatic reaction after LE. We suggest that systematic measurement
      of serum pancreatic enzymes should be performed in cases of abdominal pain
      following selective LE and transarterial chemoembolization in order to confirm
      acute pancreatitis after embolization, which can clinically mimic a
      postembolization syndrome.

PMID- 17449967
TI  - Prevalence of primary fungal infections in necrotizing pancreatitis.
AB  - BACKGROUND/AIMS: Prophylactic use of carbapenems (meropenem and imipenem) and
      other broad-spectrum antibiotics in necrotizing pancreatitis has been suggested
      as a risk factor for pancreatic fungal infections. The aim of our study was to
      determine the prevalence of primary fungal infections and the pattern of
      antibiotic use in necrotizing pancreatitis at our institution. METHODS: Records
      on 689 consecutive patients with acute pancreatitis between 2000 and 2004 were
      reviewed. Necrotizing pancreatitis was identified by contrast-enhanced computed
      tomography (CT) scan. Data on antibiotic usage were collected and microbiologic
      data obtained from radiologic, endoscopic, and surgical interventions (pancreatic
      aspiration, drain placement or debridement) were reviewed for evidence of fungal
      infection. Pancreatic fungal infections were classified as primary if the
      positive culture was obtained at the time of initial intervention. RESULTS: Among
      64 patients with necrotizing pancreatitis, there were no cases of primary
      pancreatic fungal infections and 7 cases (11%) of secondary pancreatic fungal
      infections. Fifteen patients (23%) developed pancreatic bacterial infections.
      Among 62 patients with necrotizing pancreatitis in whom antibiotic exposure was
      known, 45% received carbapenems for a median duration of only 6 days, and 84%
      received non-carbapenem antibiotics for a median duration of 14 days. CONCLUSION:
      Limited use and short duration of carbapenem therapy may be factors contributing
      to the absence of primary fungal infections in our study.

PMID- 17449968
TI  - Acute pancreatitis affects non-parenchymal liver cells by a mechanism dependent
      on platelet-activating factor.
AB  - BACKGROUND/AIM: During acute experimental pancreatitis, inflammatory
      mediators/cytokines are released by the pancreas and enter the portal venous
      system, reaching the liver. We investigate some aspects of the liver cell
      function under conditions of acute pancreatitis and the effect of in vivo
      treatment with a selective platelet-activating factor (PAF) antagonist. METHODS:
      Cells were isolated from Wistar rats 24 h after induction of acute pancreatitis
      by retrograde injection of sodium taurocholate into the main pancreatic duct. The
      non-parenchymal cell population was separated by Percoll gradient and the
      adherent cell population (Kupffer cells) obtained. The cells were cultured for 24
      h and supernatants assayed for nitrite by Griess reaction and for tumour necrosis
      factor (TNF) by bioassay in L929 cells. The microbicidal activity was evaluated
      by killing of Candida albicans. The PAF antagonist WEB2170 (10 mg/kg i.v.) was
      administered 30 min before induction of pancreatitis. RESULTS: We found that
      liver cells produce nitric oxide (NO) only under lipopolysaccharide stimulation
      and that WEB-2170 treatment reduces the NO production by liver cells in the
      pancreatitis group only. Cells from both groups produced TNF spontaneously, and
      the levels were further increased after lipopolysaccharide stimulation. WEB-2170
      treatment did not affect the TNF levels. Moreover, killing of C. albicans by
      Kupffer cells wassignificantly increased by the PAF antagonist. CONCLUSION: These
      results suggest that PAF released during acute pancreatitis upregulates the NO
      production by non-parenchymal liver cells and inhibits Kupffer cell microbicidal
      activity which could explain the increased bacterial dissemination observed in
      acute pancreatitis.

PMID- 17449969
TI  - EUS-assisted rendezvous stenting of the pancreatic duct for chronic calcifying
      pancreatitis with multiple pseudocysts.
AB  - INTRODUCTION: The best choice of endoscopic drainage of pancreatic pseudocysts
      complicating chronic pancreatitis is currently unknown, with EUS-guided
      transmural drainage competing with ERCP transpapillary techniques. However,
      recent studies currently recommend the use of both techniques in complex cases.
      CASE PRESENTATION: We present the case of a 60-year-old male patient with chronic
      calcifying pancreatitis, with severe ductal obstruction and multiple
      communicating pancreatic pseudocysts. The patient presented in the emergency
      department with weight loss, jaundice, steatorrhea and diabetes. Initial imaging
      evaluation (by transabdominal US, EUS and MRCP) depicted a dilated common bile
      duct, intrahepatic bile ducts and dilated main pancreatic duct (up to 1 cm) with
      multiple stones, as well as three pseudocysts at the level of the pancreatic head
      and one pseudocyst at the level of the pancreatic tail. ERCP with direct
      cannulation and transpapillary drainage of the bile duct or pancreatic duct was
      unsuccessful. Consequently, a EUS-assisted rendezvous stenting of the pancreatic
      duct was done, with the transpapillary placement of a 5-cm stent. Biliary
      cannulation was also possible with the placement of a double pigtail 9-cm stent
      in the common bile duct. Subsequent evolution was rapidly favorable with the
      disappearance of the pancreatic pseudocysts on the control CT after 24 h.
      CONCLUSION: Our case clearly showed the benefit of combined draining procedures
      even in cases of chronic pancreatitis with multiple pseudocysts where surgical
      drainage was previously deemed necessary.

PMID- 17449970
TI  - (Non-)compliance with guidelines for the management of severe acute pancreatitis
      among German surgeons.
AB  - BACKGROUND: Implementation of guidelines for the therapy of acute pancreatitis
      (e.g. those of the International Association of Pancreatology, IAP) into clinical
      practice has been assumed but not been evaluated. AIM: To verify the knowledge
      and acceptance of guidelines for the management of severe acute pancreatitis
      among German surgeons. METHODS: A questionnaire consisting of five short
      questions concerning key points in the management of severe acute pancreatitis
      was sent to the chairmen of the departments of general and visceral surgery of 39
      university and 316 non-university hospitals in Germany. An additional, more
      detailed questionnaire accompanied the audit of the university chairmen. RESULTS:
      The response rate was 62%. 11% stated that they strictly followed all guidelines
      (IAP recommendations No. 2-6), 31% followed all but one recommendation, 31% did
      not follow 2 or more of the guidelines, and the answers of 27% suggested that
      their treatment differed substantially from the guideline recommendations. For
      example, fine needle aspiration biopsy, recommended to differentiate between
      infected and sterile necrosis in patients with signs of sepsis, was not performed
      by 55%, and prophylactic antibiotics, recommended to prevent secondary infection
      of pancreatic necrosis, were not given by 20%. CONCLUSION: German surgeons know
      the IAP recommendations for the management of severe acute pancreatitis and have
      implemented these guidelines in clinical practice. This, however, does not mean
      that all guideline concepts are strictly followed.

PMID- 17449971
TI  - Severe complication of pancreatitis - huge retroperitoneal abscess formation.

PMID- 17449972
TI  - Current concepts on the functional somatic syndromes and temporomandibular
      disorders.
AB  - BACKGROUND: The importance of psychosocial factors in the etiopathogenesis of
      temporomandibular disorders (TMD) has led to the hypothesis that these disorders
      may be part of a wider group of somatoform disorders, the functional somatic
      syndromes (FSS). Types of studies reviewed. The present paper is an overview
      summarizing the current concepts on the TMD-FSS relationship. A non-systematic
      search in the Medline database identified peer-reviewed papers on the
      epidemiological and clinical characteristics of the complex groups of disorders
      labelled functional somatic syndromes, focusing on the common features to
      temporomandibular disorders patients. RESULTS: Literature data suggest that FSS
      and TMD share many etiopathogenetic and epidemiological features, both groups of
      disorders having a multifactorial etiopathogenesis and needing a
      multidisciplinary approach to diagnosis and treatment. Psychosocial
      characteristics of patients seem to have many similarities and the prevalence of
      Axis I psychiatric disorders is elevated. The majority of studies focused on the
      relationship between TMD and fibromyalgia (FM), due to the high rate of orofacial
      involvement related to FM. Clinical implications. The presence of common features
      between TMD and FSS patient may suggest the need for changes in the diagnostic
      and therapeutic approach to TMD patients, with the introduction of treatment
      protocols which also address the psychosocial impairment accompanying TMD
      symptoms, in order to overcome the limits of traditional therapies.

PMID- 17449973
TI  - General health of dentists. Literature review.
AB  - The studies show a dental practitioner as a subject of a wide variety of physical
      and psychological ailments. It is induced or aggravated by the work specificity
      and greatly affects the health of dental professionals. Therefore, general health
      of dentists, especially effect of dental activity on it, is present-day,
      important and as a matter of fact not well documented subject. The aim of our
      review is to summarize and ascertain dental practice-related disorders
      influencing the physical and psychological health of practitioner. Also we would
      like to highlight the most vulnerable systems of the dental professional and to
      survey the best methods to overcome these ailments. RESULTS: There is growing
      body of evidence that suggests surprisingly high vulnerability within the dental
      profession to certain disorders and afflictions that can be categorized as
      practice-related. CONCLUSIONS: In different countries dentists reported having
      poor general health and suffer from various health-related problems. To enjoy and
      be satisfied with their professional and personal lives, dentists must be aware
      of the importance to maintain good physical and mental health.

PMID- 17449974
TI  - A pilot study of Er,Cr:YSGG laser therapy used as an adjunct to scaling and root
      planing in patients with early and moderate periodontitis.
AB  - OBJECTIVES: The study aim was to compare the results of an Er,Cr:YSGG laser
      therapy used in adjunct to scaling and root planing (SRP), and of SRP alone, in a
      small group of patients with early to moderate periodontitis. MATERIALS AND
      METHODS: Ten adult patients with periodontitis were treated according to split
      mouth design, using Protocol A (SRP alone) or, Protocol B (Er;Cr:YSGG laser
      therapy combined with SRP). At baseline, and 3 months after the treatment the
      following periodontal parameters were evaluated: bleeding on probing (BOP),
      probing depth (PD), plaque index (PI). RESULTS: no statistically significant
      difference in plaque levels was noted before and after the treatment between the
      treated quadrants, however a tendency of a more pronounced decrease in plaque
      levels was noted in the group of laser-SRP treated teeth. After three months, 60
      68% decrease of BOP-positive teeth compared to baseline status was noted in all
      treated quadrants, without significant difference between the treatment modes.
      The decrease of mean PD values was measured after three months compared to
      baseline: on the lingual surfaces in 'SRP" group the mean PD improvement value
      was 0,94+/-12, and in the laser-SRP group it was 1,96+/-11, (p<0,001); on the
      vestibular surfaces the mean improvement values were 0,99+/-0,14 and 2,03+/-0,11,
      respectively (p<0,001). CONCLUSIONS: Non-surgical periodontal therapy using both
      an Er;Cr:YSGG laser + SRP and SRP alone, lead to significant improvements in all
      the investigated clinical parameters. The combined treatment using laser as an
      adjunct to root scaling and planing seemed to be advantageous when compared to
      SRP alone, due to more efficient attachment level restoration.

PMID- 17449975
TI  - A three-dimensional model of the human masticatory system, including the
      mandible, the dentition and the temporomandibular joints.
AB  - The objective of this study was to create a three-dimensional mathematical model
      of a human masticatory system, including the mandible, the dentition and the
      temporomandibular joints. Object of research was one 20 year old dead man. The
      research was approved by Committee of bioethics (Kaunas University of Medicine).
      Required extent of computed tomography scanning and required high amount and high
      resolution of images increased X-ray radiation for the object and made this
      research impossible to perform on alive human. Spiral computed tomography
      scanning was performed to achieve two-dimensional images, necessary for creating
      three-dimensional model. The 3D modeling was done using the "Image pro plus" and
      "Imageware"software. A three-dimensional physiological (normal) model of a human
      masticatory system, simulating the mandible, the dentition and the
      temporomandibular joints was generated. This model system will be used
      subsequently in stress analysis comparison for the physiological and pathological
      systems after improvement of its physical properties. We suggest that computer
      simulation is a promising way to study musculoskeletal biomechanics of
      masticatory system.

PMID- 17449976
TI  - Rehabilitation medicine: the Asian perspective.

PMID- 17449977
TI  - Long-term survival in Werdnig-Hoffmann disease.
AB  - OBJECTIVES: To report long-term survival of spinal muscular atrophy type 1 (SMA
      1) and consequences on speech and ventilator dependence as a function of mode of
      ventilator use. DESIGN: A retrospective chart review of 106 consecutively
      referred SMA 1 patients, the 92 most severe of which were considered in three
      groups: untreated (group 1), tracheostomy managed (group 2), and noninvasively
      managed (group 3). RESULTS: The untreated patients died at 9.6 +/- 4.0 mos of
      age. The mean age of the 22 patients referred with tracheostomy tubes (group 2)
      was 70.5 +/- 43.3 mos (range 2-159 mos); five died at 66.2 +/- 114.2 mos (range 8
      270 mos) of age. Six had comprehendible speech at the time of tracheotomy and
      retained some ability to vocalize afterward. None of the 21 patients who had not
      developed the ability to speak did so after tracheotomy. Twenty-five of the 27
      total lost all autonomous breathing ability immediately, and definitively, after
      tracheotomy. The 47 patients who used noninvasive mechanical ventilation (NIV)
      (group 3) were extubated to it during episodes of acute respiratory failure.
      Thirty-nine of these were 65.2 +/- 45.8 mos (range 11-153 mos) of age, and eight
      died at 60.9 +/- 26.1 mos (range 36-111 mos) of age. There was no significant
      difference in longevity with or without tracheostomy, but the NIV patients had
      significantly fewer (P = 0.04) hospitalizations per year after age 5; 39 of the
      47 could communicate verbally, and only nine were continuously dependent on NIV.
      CONCLUSIONS: NIV and tracheostomy can both prolong survival for SMA 1 patients,
      but the latter results in continuous ventilator dependence and speech does not
      develop.

PMID- 17449979
TI  - Medical considerations of long-term survival of Werdnig-Hoffmann disease.
AB  - OBJECTIVES: To report intercurrent nonrespiratory complications of unprecedented
      survival for Werdnig-Hoffman disease (spinal muscular atrophy type 1 [SMA 1]).
      DESIGN: A retrospective chart review and caregiver questionnaire for 103
      consecutively referred SMA 1 patients for whom death was prevented during
      infancy. RESULTS: Overall, 15 of 63 (23.8%) respondents had severe, symptomatic
      bradycardias. Thirteen of 25 males had bilateral cryptorchidism, and two were
      unilateral. Ten of 42 (24%) respondents had recurrent oral candidiasis, and eight
      (19.0%) had recurrent nonoral candidiasis. All patients had hip
      dislocation/subluxation. They had collapsing spines and scoliosis by 1 yr of age.
      Ninety-six had indwelling gastrostomy/nasogastric tubes before 24 mos of age.
      Twenty-six underwent fundoplication to decrease reflux. Fifty-seven were on
      modified elemental diets with reported benefits. About one half had early
      pubarche. Three patients had episodes of acute pancreatitis. One untreated
      patient died of candidal endocarditis at 4 mos of age, and a second child had
      mitral valve candidiasis on autopsy. CONCLUSION: Prolonged survival of SMA 1
      results in a high incidence of concomitant medical conditions that need to be
      addressed.

PMID- 17449980
TI  - The impact of the inpatient rehabilitation facility prospective payment system on
      stroke program outcomes.
AB  - OBJECTIVE: To examine the impact of the Medicare inpatient rehabilitation
      facility (IRF) prospective payment system (PPS) on outcomes in a stroke
      rehabilitation program. DESIGN: An analysis was performed on a database including
      945 stroke patients admitted to an inpatient stroke rehabilitation program 5 yrs
      before implementation of the IRF PPS and 3.5 yrs after implementation. Patients
      were classified with regard to stroke location (left vs. right), level of
      cognitive impairment, presence/absence of unilateral neglect, and level of
      depressive symptomatology. Functional status was evaluated at time of admission
      and discharge by functional independence measure (FIM). Other outcome measures
      included length of stay (LOS) and discharge destination. The impact of IRF PPS on
      LOS, progress in rehabilitation, and discharge destination was examined via
      univariate analyses of covariance and logistic regression. RESULTS: Patients
      admitted after implementation of the IRF PPS had shorter LOS but made less
      progress, had lower functional levels at discharge, and had higher rates of
      institutional discharge. CONCLUSIONS: Although associated with decreased LOS,
      implementation of the IRF PPS was associated with decreased functional gains,
      lower discharge FIM levels, and higher rates of institutional discharge. Cost
      savings associated with the PPS must be considered in light of these untoward
      outcomes.

PMID- 17449981
TI  - The clinician effect on "objective" technical components of the electrodiagnostic
      consultation.
AB  - OBJECTIVE: To examine the impact of clinician factors on technical data within an
      electrodiagnostic consultation for low-back pain and spinal stenosis. DESIGN:
      Examiner differences on single-segment paraspinal mapping scores and other
      findings were examined in a prospective, masked, double-controlled trial
      involving 150 people aged 55-80 yrs who were selected for no symptoms, back pain,
      or possible spinal stenosis. RESULTS: Unmasked clinicians were more variable than
      masked physicians (F2,219 = 4.808, P =or<0.01) and gave lower scores to people
      they felt had mechanical back pain. The percentage of inadequate segmental scores
      differed among clinicians (0-16.6%, F8,226 = 4.170, P < 0.001), with fellows
      having more difficulty than faculty (11.76 +/- 32.38% vs. 0.75 +/- 8.67%) (t233 =
      3.753, P < 0.001). Correction of clinician bias improved the relationship between
      paraspinal score and subjects' ability to walk (weighted regression R = 0.129, B
      = -0.047, P < 0.001; unweighted regression R = 0.090, B = -0.045, P < 0.001).
      CONCLUSIONS: Objective testing is adversely affected by clinician factors
      including prejudgment, experience, and individual idiosyncrasies. Less variation
      is found in more codified procedures. For electrodiagnostic consultation,
      correction of variability improves the relationship of test results to
      disability.

PMID- 17449983
TI  - Factors associated with health-related quality of life in chronic spinal cord
      injury.
AB  - OBJECTIVE: An important goal of rehabilitation and treatment after spinal cord
      injury (SCI) is to improve function and enhance health-related quality of life
      (HRQoL). However, previous assessments are limited by use of HRQoL instruments
      not specific to SCI. Although respiratory dysfunction is common in SCI, it has
      not been possible to assess the association of comorbid medical conditions,
      including respiratory symptoms and pulmonary function, to HRQoL. Therefore, we
      assessed whether these factors were associated with HRQoL in SCI using an SCI
      specific HRQoL questionnaire. DESIGN: In our cross-sectional study, 356
      participants >or=1 yr post-SCI completed a 23-item SCI-specific HRQoL
      questionnaire and a detailed health questionnaire, and underwent pulmonary
      function testing and a neurological exam at VA Boston between 1998 and June 2003.
      RESULTS: In a multivariate regression model, age, employment status, motor level
      and completeness of injury, and ambulatory mode (use of hand-propelled or
      motorized wheelchair, use of crutches or canes, or walking independently) were
      independently associated with HRQoL. After adjusting for these factors, chronic
      cough, chronic phlegm, persistent wheeze, dyspnea with activities of daily
      living, and lower forced expiratory volume in 1 sec and forced vital capacity
      were each associated with a lower HRQoL. CONCLUSIONS: These results provide
      evidence for the clinical validity of our SCI-specific HRQoL instrument. We also
      identify potentially modifiable factors that, if addressed, may lead to HRQoL
      improvement in SCI.

PMID- 17449984
TI  - Dry needling to a key myofascial trigger point may reduce the irritability of
      satellite MTrPs.
AB  - OBJECTIVE: To investigate the changes in pressure pain threshold of the secondary
      (satellite) myofascial trigger points (MTrPs) after dry needling of a primary
      (key) active MTrP. DESIGN: Single blinded within-subject design, with the same
      subjects serving as their own controls (randomized). Fourteen patients with
      bilateral shoulder pain and active MTrPs in bilateral infraspinatus muscles were
      involved. An MTrP in the infraspinatus muscle on a randomly selected side was dry
      needled, and the MTrP on the contralateral side was not (control). Shoulder pain
      intensity, range of motion (ROM) of shoulder internal rotation, and pressure pain
      threshold of the MTrPs in the infraspinatus, anterior deltoid, and extensor carpi
      radialis longus muscles were measured in both sides before and immediately after
      dry needling. RESULTS: Both active and passive ROM of shoulder internal rotation,
      and the pressure pain threshold of MTrPs on the treated side, were significantly
      increased (P < 0.01), and the pain intensity of the treated shoulder was
      significantly reduced (P < 0.001) after dry needling. However, there were no
      significant changes in all parameters in the control (untreated) side. Percent
      changes in the data after needling were also analyzed. For every parameter, the
      percent change was significantly higher in the treated side than in the control
      side. CONCLUSIONS: This study provides evidence that dry needle-evoked
      inactivation of a primary (key) MTrP inhibits the activity in satellite MTrPs
      situated in its zone of pain referral. This supports the concept that activity in
      a primary MTrP leads to the development of activity in satellite MTrPs and the
      suggested spinal cord mechanism responsible for this phenomenon.

PMID- 17449985
TI  - Measurement of plantarflexor spasticity in traumatic brain injury: correlational
      study of resistance torque compared with the modified Ashworth scale.
AB  - OBJECTIVES: To examine the usefulness of a biomechanical measure, resistance
      torque (RT), in quantifying spasticity by comparing its use with a clinical
      scale, the modified Ashworth scale (MAS), and quantitative electrophysiological
      measures. DESIGN: This is a correlational study of spasticity measurements in 34
      adults with traumatic brain injury and plantarflexor spasticity. Plantarflexor
      spasticity was measured in the seated position before and after cryotherapy using
      the MAS and also by strapping each subject's foot and ankle to an apparatus that
      provided a ramp and hold stretch. The quantitative measures were (1) reflex
      threshold angle (RTA) calculated through electromyographic signals and joint
      angle traces, (2) Hdorsiflexion (Hdf)/Hcontrol (Hctrl) amplitude ratio obtained
      through reciprocal inhibition of the soleus H-reflex, (3) Hvibration (Hvib)/Hctrl
      ratio obtained through vibratory inhibition of the soleus H-reflex, and (4) RT
      calculated as the time integral of the torque graph between the starting and
      ending pulses of the stretch. RESULTS: Correlation coefficients between RT and
      MAS scores in both pre-ice (0.41) and post-ice trials (0.42) were fair (P =
      0.001). The correlation coefficients between RT scores and RTA scores in both the
      pre-ice (0.66) and post-ice trials (0.75) were moderate (P <or= 0.001).
      CONCLUSION: RT is a measure of the cumulative torque during an imposed stretch.
      The MAS is a subjective measure of the cumulative resistance perceived by the
      clinician during an imposed stretch. RT seems to be a fair quantitative correlate
      of the MAS in assessing spasticity.

PMID- 17449986
TI  - Motor neuron inhibition-based gene therapy for spasticity.
AB  - Spasticity is a condition resulting from excess motor neuron excitation, leading
      to involuntary muscle contraction in response to increased velocity of movement,
      for which there is currently no cure. Existing symptomatic therapies face a
      variety of limitations. The extent of relief that can be delivered by ablative
      techniques such as rhizotomy is limited by the potential for sensory denervation.
      Pharmacological approaches, including intrathecal baclofen, can be undermined by
      tolerance. One potential new approach to the treatment of spasticity is the
      control of neuromuscular overactivity through the delivery of genes capable of
      inducing synaptic inhibition. A variety of experiments in cell culture and animal
      models have demonstrated the ability of neural gene transfer to inhibit neuronal
      activity and suppress transmission. Similarly, enthusiasm for the application of
      gene therapy to neurodegenerative diseases of motor neurons has led to the
      development of a variety of strategies for motor neuron gene delivery. In this
      review, we discuss the limitations of existing spasticity therapies, the
      feasibility of motor neuron inhibition as a gene-based treatment for spasticity,
      potential inhibitory transgene candidates, strategies for control of transgene
      expression, and applicable motor neuron gene targeting strategies. Finally, we
      discuss future directions and the potential for gene-based motor neuron
      inhibition in therapeutic clinical trials to serve as an effective treatment
      modality for spasticity, either in conjunction with or as a replacement for
      presently available therapies.

PMID- 17449987
TI  - Spinal injury mimicking lumbosacral plexopathy.

PMID- 17449988
TI  - Long-term use of controlled-release oxycodone for noncancer pain: results of a 3
      year registry study.
AB  - OBJECTIVE: To evaluate the outcomes associated with the use of controlled-release
      (CR) oxycodone for up to 3 years in the treatment of noncancer pain. METHODS:
      Adult patients who previously participated in controlled trials of CR oxycodone
      for osteoarthritis pain, diabetic neuropathy pain, or low back pain, and who
      continued to require opioid analgesia for moderate or severe pain, were enrolled
      in an open-label, uncontrolled, registry study. Data collected over time included
      dose, pain severity on a numeric scale, treatment acceptability, adverse events,
      and descriptions of problematic drug-related behavior. RESULTS: Two hundred
      thirty-three patients were enrolled. When the study closed, 141, 86, and 39
      patients had taken CR oxycodone for at least 1, 2, and 3 years, respectively;
      mean duration of treatment was 541.5 days. Among the 219 intent-to-treat patients
      (received at least 1 dose and provided at least 1 postdose study observation),
      the mean (SD, range) daily dose was 52.5 (+/-38.5, 10.0 to 293.5) mg. Before the
      end of month 3, 44% required an increase in total daily dose; this dropped to 23%
      during months 4 to 6, to 17% during months 10 to 12, and remained at
      approximately 10% for each time interval thereafter (range 8% to 13%). Among the
      large majority of patients with stable or lower dose requirements after the
      initial 3 months of treatment, the average pain intensity ratings were unchanged
      or improved for approximately 70% to 80% of patients at all subsequent time
      points through month 33, and for 54% (7/13 patients) at month 36. A decrease in
      pain was initially seen by the end of month 3, and for the majority of patients,
      the Average Pain Intensity score remained the same, better, or minimally worse
      (<3 points) for the remainder of the 3-year study period. The most common adverse
      events were constipation and nausea, and the incidence of these events declined
      over time on treatment. Investigators reported 6 cases (2.6%) of possible drug
      misuse but no evidence of de novo addiction was observed. DISCUSSION: These
      registry data demonstrate that a subgroup of patients with noncancer pain
      experienced prolonged relief with tolerable side effects and modest need for dose
      escalation during long-term therapy with CR oxycodone.

PMID- 17449989
TI  - How effective is long-term opioid therapy for chronic noncancer pain?

PMID- 17449990
TI  - Opioids: after thousands of years, still getting to know you.

PMID- 17449991
TI  - Psychiatric history and psychologic adjustment as risk factors for aberrant drug
      related behavior among patients with chronic pain.
AB  - OBJECTIVE: To investigate the role of psychiatric history and psychologic
      adjustment on aberrant drug-related behavior among patients prescribed opioids
      for noncancer pain. METHODS: Two hundred twenty-eight patients prescribed opioids
      for chronic pain were classified as either high or low on psychiatric morbidity
      on the basis of their responses on the psychiatric subscale of the Prescription
      Drug Use Questionnaire (PDUQ). They also completed the Brief Pain Inventory
      (BPI), Screener and Opioid Assessment for Pain Patients (SOAPP), and the Current
      Medication Misuse Measure (COMM). Patients were followed for 5 months and
      submitted a urine toxicology screen, and their treating physician completed the
      Prescription Opioid Therapy Questionnaire (POTQ). On the basis of the results
      from the SOAPP, COMM, POTQ, and urine screens, patients were classified as
      positive or negative on the Drug Misuse Index (DMI). RESULTS: One hundred and
      three (N=103) of the patients (45%) were classified in the low psychiatric group
      (Low Psych) whereas 55% (N=125) were classified in the high psychiatric morbidity
      group (High Psych). High Psych patients were significantly younger than Low Psych
      patients and had been taking opioids longer (P<0.05). The High Psych group showed
      significantly higher SOAPP and COMM scores than the Low Psych patients (P<0.001),
      had a greater frequency of abnormal urine toxicology screens (P<0.01), and
      significantly higher scores on the DMI (P<0.001). A consistent association was
      found between psychiatric morbidity and prescription opioid misuse in chronic
      pain patients. DISCUSSION: Psychiatric factors, such as a history of mood
      disorder, psychologic problems, and psychosocial stressors, may place patients at
      risk for misuse of prescription opioids. Future studies to elucidate the risk of
      medication misuse and aberrant drug behavior among this patient population are
      needed.

PMID- 17449992
TI  - Effect of acupuncture-like electrical stimulation on chronic tension-type
      headache: a randomized, double-blinded, placebo-controlled trial.
AB  - OBJECTIVE: The aim of this study was to examine the effect of acupuncture-like
      electrical stimulation on chronic tension-type headache (TTH) in a randomized,
      double-blinded, placebo-controlled study. METHODS: Thirty-six patients (18 men,
      18 women) with chronic TTH in accordance with the criteria of International
      Headache Society were investigated. The patients were randomly assigned into 2
      groups: a treatment group and a placebo group. Pain duration, pain intensity on a
      0 to 10 cm visual analog scale, number of headache attacks, and use of medication
      were recorded in a diary for 2 weeks before treatment (baseline), early stage of
      treatment (Treat-1; 2 wk), late stage of treatment (Treat-2; 4 wk), and after the
      end of treatment (Post-1, Post-2, Post-3 corresponding to 2, 4, and 6-wk follow
      up). The patients also provided an overall evaluation of the treatment effect at
      each stage. Patients were taught how to use either an acupuncture-like electrical
      stimulator or a sham stimulator (identical but incapable of delivering an
      electric current) and then instructed to use the device at home. Six acupoints,
      bilateral EX-HN5, GB 20, LI 4, were selected to be stimulated 3 minutes for each
      point, twice a day. Friedman repeated measure analysis of variance on rank was
      used to test the data. RESULTS: The pain duration was shortened at Treat-1 and
      pain intensity was decreased at Treat-1 and Treat-2 compared with baseline. The
      overall evaluation of the 2 treatments indicated improvements in both the
      treatment and the placebo groups, but with no significant difference between the
      groups (P>0.061). Despite the apparent improvement in both the treatment and
      placebo groups, a decrease in analgesic use was only observed in the treatment
      group. There was also a significant positive correlation between the reported
      intensity of the stimulus-evoked sensation and the evaluation of the effect of
      either active or placebo treatments (P=0.039). CONCLUSIONS: The use of
      acupuncture-like electrical stimulation was not associated with significant
      adverse effects. These results indicate that acupuncture-like electrical
      stimulation is a safe and potentially analgesic-sparing therapy that may be
      considered as an adjunctive treatment for patients with chronic TTH although the
      clinical effect on pain seems to be marginal in the present set-up.

PMID- 17449993
TI  - Thermal and visceral hypersensitivity in irritable bowel syndrome patients with
      and without fibromyalgia.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder
      characterized by both visceral and somatic hyperalgesia, producing a similar
      effect seen with the central hypersensitivity mechanism in fibromyalgia (FM).
      OBJECTIVES: The aim of the current study was to compare magnitudes of visceral
      and thermal hypersensitivity in IBS patients and FM patients with IBS (FM+IBS)
      compared with healthy controls. METHODS: Female patients with IBS (n=12), FM+IBS
      (n=12), and control participants (n=13) rated pain intensity to hot water
      immersion (45 and 47 degrees C) of the hand/foot and to phasic distension of the
      rectum (35, 55 mm Hg) on a Mechanical Visual Analog Scale. The data were analyzed
      with 3 separate 1-way analyses of variance with post hoc Tukey tests. RESULTS:
      For both thermal and visceral stimuli, the control group had lower pain ratings
      than either the IBS or FM+IBS groups (P<0.001). IBS patients rated rectal
      distension as more painful than the FM+IBS group (P=0.005). During hot water
      immersion of the foot, the FM+IBS group had higher pain ratings than the IBS
      group (P<0.001). During hand immersion, FM+IBS and IBS patients did not
      significantly differ in their pain intensity ratings (P=0.4). CONCLUSIONS: FM+IBS
      patients show greater thermal hypersensitivity compared with IBS patients.
      However, IBS patients exhibit higher pain ratings to rectal distension compared
      with FM+IBS patients. This data suggests that regions of primary and secondary
      hyperalgesia are dependent on the primary pain complaint.

PMID- 17449994
TI  - Making pain assessment more accessible to children and parents: can greater
      involvement improve the quality of care?
AB  - OBJECTIVES: To determine whether nursing and parental pain assessment
      documentation and analgesia administration increased with the use of a temporary
      tattoo of a pain intensity scale (TTPS) compared with a paper version of the pain
      scale (PPS). To document any adverse skin reactions from the use of the TTPS and
      to assess the feasibility and acceptability of the PPS and TTPS for use as
      postoperative pain assessment tools in the home and clinical setting. METHODS:
      Two pilot randomized controlled trials were conducted to test the TTPS
      intervention and the PPS control condition in children aged 6 to 12 years, after
      surgery. Trial 1 involved children admitted to hospital for planned inpatient
      surgery (n=86). Trial 2 involved children discharged home following day case
      surgery (n=25). RESULTS: The TTPS was well accepted and there were no adverse
      effects. Our hypothesis that the TTPS would increase documentation of pain
      assessment or analgesic administration was not supported. However, a number of
      confounding factors may explain the findings. Children in both trials indicated
      greater overall satisfaction with the TTPS and responses from both parents and
      children suggested some aspects of the quality of the pain management experience
      were enhanced with use of the TTPS in both trials. DISCUSSION: The TTPS is a new
      method to engage children in pain assessment, which may have positive effects on
      the quality of postoperative pain assessment and management in hospital and home
      settings. Larger trials are needed to determine the effectiveness of the TTPS
      across all pediatric settings and for children with nonsurgical and also surgical
      pain. The findings from these pilot trials provide useful information for design
      and power estimation for further research in inpatient and home settings.

PMID- 17449995
TI  - Reproducibility of pressure pain threshold and visual analog scale findings in
      chronic whiplash patients.
AB  - BACKGROUND: Assessment of pain in patients with whiplash-associated disorders has
      been previously reported using a variety of instruments. However, the
      reproducibility of the findings derived from such measurements has not been
      explored with respect to this particular patients group. OBJECTIVES: To evaluate
      the intratester and intertester reproducibility of pressure pain threshold (PPT)
      findings and the intratester reproducibility of visual analog scale (VAS)
      findings relating to the cervical region of chronic whiplash patients for the
      determination of smallest real difference values. METHODS: Twenty-one chronic
      whiplash patients: 13 women and 8 men participated in this study. The intratester
      paradigm was based on 2 testing sessions over a period of 5 to 11 days (7.95+/
      1.90) and incorporated recording of VAS scores and also PPT scores relating to 3
      pairs of right and left homologous cervical sites. The intertester study was
      conducted within the first testing session and referred to the PPT measurement
      only. In this session, patients were also asked to fill in the Neck Disability
      Index questionnaire. RESULTS: The interclass correlation coefficient-derived
      reproducibility of the PPT scores was good to excellent within and between
      testers ranging 0.85 to 0.91 and 0.88 to 0.97, respectively. There was, however,
      a significant difference between the testers. The VAS scores demonstrated lower
      reproducibility (interclass correlation coefficient=0.67). On the basis of the
      standard error of measurement, the smallest real difference of PPT ranged 40.2 to
      58.9 kPa whereas the corresponding figure for the VAS was 3.76 cm. CONCLUSIONS:
      On the basis of the current patient sample, this study demonstrates that although
      PPT findings may generally be applied for monitoring change in chronic whiplash
      patients, the use of VAS scores should be limited to patients whose initial score
      is above 4. It is also suggested that if the PPT is to serve as an outcome
      measure, its measurement should be performed by the same tester.

PMID- 17449996
TI  - Increased pericranial tenderness, decreased pressure pain threshold, and headache
      clinical parameters in chronic tension-type headache patients.
AB  - OBJECTIVE: The aim was to investigate whether increased pericranial tenderness or
      decreased pressure pain threshold (PPT) was related to headache intensity,
      duration, and frequency in chronic tension-type headache (CTTH). METHODS: Twenty
      five CTTH patients and 25 matched controls were studied. A headache diary was
      kept for 4 weeks to substantiate the diagnosis and record the pain history. Three
      tenderness (total, cephalic, and neck) scores and PPT at both cephalic and neck
      points were objectively and blinded assessed. Bodily pain perceived by the
      patients was assessed with the Short Form-36 questionnaire. RESULTS: CTTH
      patients showed decreased PPT and increased tenderness as compared with controls
      (P<0.001). Negative correlations were found between PPT on each point and their
      respective tenderness scores. Within the CTTH group, neither increased tenderness
      nor decreased PPT seemed to directly influence headache intensity, frequency or
      duration; or vice versa. DISCUSSION: Increased tenderness may predispose the
      patients to other perpetuating factors in inducing headache attacks. Further
      research is needed to clearly define the role of pericranial tender tissues or
      other factors in the genesis and maintenance of CTTH.

PMID- 17449997
TI  - Prevalence of and referred pain from myofascial trigger points in the forearm
      muscles in patients with lateral epicondylalgia.
AB  - OBJECTIVE: Referred pain and pain characteristics evoked from the extensor carpi
      radialis brevis, extensor carpi radialis longus, extensor digitorum communis, and
      brachioradialis muscles was investigated in 20 patients with lateral
      epicondylalgia (LE) and 20-matched controls. METHODS: Both groups were examined
      for the presence of myofascial trigger points (TrPs) in a blinded fashion. The
      quality and location of the evoked referred pain, and the pressure pain threshold
      (PPT) at the lateral epicondyle on the right upper extremity (symptomatic side in
      patients, and dominant-side on controls) were recorded. Several lateral elbow
      pain parameters were also evaluated. RESULTS: Within the patient group, the
      elicited referred pain by manual exploration of 13 out of 20 (65%) extensor carpi
      radialis brevis muscles, 12/20 (70%) extensor carpi radialis longus muscles,
      10/20 (50%) brachioradialis muscles, and 5/20 (25%) extensor digitorum communis
      muscles, shares similar pain patterns as their habitual lateral elbow and forearm
      pain. The mean number of muscles with TrPs for each patient was 2.9 [95%
      confidence interval (CI) 1,4] of which 2 (95% CI 1,3) were active, and 0.9 (95%
      CI 0,2) were latent TrPs. Control participants only had latent TrPs (mean: 0.4;
      95% CI 0,2). TrP occurrence between the 2 groups was significantly different for
      active TrPs (P<0.001), but not for latent TrPs (P>0.05). The referred pain
      pattern was larger in patients than in controls, with pain referral to the
      lateral epicondyle (proximally) and to the dorso-lateral aspect of the forearm in
      the patients, and confined to the dorso-lateral aspect of the forearm in the
      controls. Patients with LE showed a significant (P<0.001) lower PPT (mean: 2.1
      kg/cm; 95% CI 0.8, 4 kg/cm) as compared with controls (mean: 4.5 kg/cm; 95% CI 3,
      7 kg/cm). Within the patient group, PPT at the lateral epicondyle was negatively
      correlated with both the total number of TrPs (rs=-0.63; P=0.003) and the number
      of active TrPs (rs=-0.5; P=0.02): the greater the number of active TrPs, the
      lower the PPT at the lateral epicondyle. DISCUSSION: Our results suggest that in
      patients with LE, the evoked referred pain and its sensory characteristics shared
      similar patterns as their habitual elbow and forearm pain, consistent with active
      TrPs. Lower PPT and larger referred pain patterns suggest that peripheral and
      central sensitization exists in LE.

PMID- 17449998
TI  - Does systematic graded exposure in vivo enhance outcomes in multidisciplinary
      chronic pain management groups?
AB  - OBJECTIVES: Graded exposure in vivo (GEXP) treatment has been successfully used
      to reduce levels of pain-related fear and disability in some chronic pain
      patients, but its effectiveness has not been evaluated in general clinical
      settings using group-design studies. The purpose of this study was to determine
      if the systematic incorporation of GEXP into a multidisciplinary chronic pain
      management group (PMG) treatment program would result in better treatment
      outcomes than usual PMG treatment. METHODS: One hundred forty-three chronic pain
      patients who were assessed as suitable for an outpatient multidisciplinary
      chronic PMG program were randomly allocated to 3 experimental conditions; usual
      PMG, PMG incorporating systematic graded exposure, and wait-list control.
      RESULTS: The clinical outcomes of the 2 treatment conditions were not
      significantly different, suggesting that the systematic incorporation of GEXP
      into a multidisciplinary PMG program did not result in better treatment outcomes
      than usual PMG treatment. Both group treatment programs were associated with
      significant treatment effects when compared with the wait-list control on
      measures of pain intensity, fear of movement/(re)injury, pain self-efficacy,
      activity level, and depression. No treatment effects were found on self-report
      measures of pain disability or anxiety. DISCUSSION: The addition of systematic
      graded exposure into a multidisciplinary chronic pain management program did not
      result in better clinical outcomes than the usual group treatment program. The
      validity of GEXP to the broader population of chronic pain patients warrants
      further investigation.

PMID- 17449999
TI  - Laser-evoked potentials correlate with clinical evolution in a case of
      spontaneous and recurrent complex regional pain syndrome type I.
AB  - We describe a case of spontaneous complex regional pain syndrome developing first
      in the left arm and 2 years later in the right foot of a 14-year-old girl.
      Physical examination showed abnormalities in tactile and thermal sensitivity.
      Laser-evoked potentials (LEPs) after stimulation of the affected right foot were
      absent in the acute phase and then progressively recovered over a period of 5
      months, in correlation with clinical changes. To our knowledge, no systematic
      analysis of LEPs in complex regional pain syndrome has been published. We suggest
      that the observed electrophysiologic alterations could result from a temporary
      dysfunction of attentional systems, which are assumed to contribute greatly to
      the LEPs vertex complex. Further studies are needed to test this hypothesis.

PMID- 17450000
TI  - The terms neurogenic pain and psychogenic pain complicate clinical practice.

PMID- 17450003
TI  - Perioperative prophylaxis for postcataract extraction endophthalmitis.

PMID- 17450004
TI  - Adnexal and anterior segment manifestations of HIV/AIDS.

PMID- 17450005
TI  - Acanthamoeba keratitis.

PMID- 17450006
TI  - Use of voriconazole in the treatment of fungal keratitis.

PMID- 17450007
TI  - Advances in Boston keratoprosthesis: enhancing retention and prevention of
      infection and inflammation.

PMID- 17450008
TI  - LASIK-associated atypical mycobacteria keratitis: a case report and review of the
      literature.

PMID- 17450009
TI  - Blebitis and endophthalmitis after glaucoma filtering surgery.

PMID- 17450010
TI  - Herpes simplex virus: an important etiology for secondary glaucoma.

PMID- 17450011
TI  - Endophthalmitis after glaucoma drainage implant surgery.

PMID- 17450012
TI  - Invasive fungal infections of the orbit.

PMID- 17450013
TI  - Syphilis: an ophthalmologic update.

PMID- 17450014
TI  - Acute retinal necrosis: an overview.

PMID- 17450015
TI  - Cytomegalovirus retinitis after one decade of HAART.

PMID- 17450016
TI  - Intraocular foreign body related endophthalmitis.

PMID- 17450017
TI  - Endogenous bacterial and fungal endophthalmitis.

PMID- 17450018
TI  - The role of inflammation and infection in age-related macular degeneration.

PMID- 17450019
TI  - Endophthalmitis associated with intravitreal injections.

PMID- 17450021
TI  - Precut papillotomy is effective and safe only "when" clinically indicated and
      "in" expert hands.

PMID- 17450022
TI  - Symptom assessment tools for gastroesophageal reflux disease (GERD) treatment.
AB  - Relief of symptoms, both typical and atypical, is the mainstay of therapy for
      patients with gastroesophageal reflux disease (GERD); however, evaluation of GERD
      symptoms' response to treatment has been hampered by the lack of a questionnaire
      that meets all the criteria of an ideal evaluative GERD symptom assessment tool.
      These criteria are: sensitivity in GERD patients, covering all symptom dimensions
      (multidimensional construct), assessment of frequency and intensity of "typical"
      and "atypical" GERD symptoms, practical and economical, easy to understand,
      responsive over short time intervals, use as a patient self-assessment tool,
      amenable to daily use, psychometrically validated, and translation into many
      languages with cross-cultural adaptation. Thus far, 14 instruments have been
      developed to assess GERD symptoms and potentially can be used to evaluate
      treatment response during a therapeutic trial in GERD patients. However,
      comparison of the different evaluative tools is needed.

PMID- 17450023
TI  - Factors predicting initial career choices in gastroenterology fellows.
AB  - BACKGROUND AND GOALS: As academic gastroenterology (GI) fellowship programs often
      gear trainee recruitment to those displaying potential for academic careers, the
      aim of the study was to determine whether predictive factors exist that determine
      whether GI fellows pursue academia versus private practice. STUDY: Educational
      file review was conducted on all GI fellows from Mayo Clinic-Rochester from 1990
      through 2003, with demographic variables extracted. The outcome of interest was
      whether the first job after fellowship was in academics or private practice.
      RESULTS: Of 92 fellows completing training, 60 accepted academic positions (65%)
      (P=0.005, 95% confidence interval: 0.55-0.74), whereas 32 (35%) pursued private
      practice. Those of Asian descent were significantly more likely to enter
      academics versus those of African American (P=0.02) or Hispanic (P=0.01) descent.
      There were nonsignificant trends of more women than men (85% vs. 62%), military
      than non-military (86% vs. 63%), bachelors of arts than science degrees (70% vs.
      50%) and advanced fellowship training than not (74% vs. 61%) going into
      academics. There was no significant difference in career choices between fellows
      entering the National Institutes of Health training tract versus the Clinical
      Scholar or Clinical Investigator tracts. There were no significant associations
      between age, marital status, hometown population, foreign medical degree,
      research mentor factors or type of research during fellowship and practice
      choice. CONCLUSIONS: Although there seem to be predictive variables in
      determining whether GI fellows enter private practice or academia, the initial
      practice choice likely results from multiple combined factors.

PMID- 17450024
TI  - Is there a seasonal variation in the incidence or intensity of allergic
      eosinophilic esophagitis in newly diagnosed children?
AB  - INTRODUCTION: Allergic eosinophilic esophagitis (AEE) is thought to be an
      allergic reaction that is characterized by inflammation caused by predominant
      accumulation of eosinophils in esophageal mucosa (> or =15 eosinophils per high
      power field). AIMS: To examine the seasonal distribution of newly diagnosed AEE
      children. METHODS: Retrospective analysis of all patients diagnosed with AEE at
      our institution over a nearly 6-year period (December 1998 to October 2004).
      RESULTS: Two hundred thirty-four children (mean age 7.3 y, median age 7.0 y, age
      range 0.2 to 19.5 y) were diagnosed with AEE during the study period.
      Significantly fewer patients were diagnosed with AEE in Winter as compared with
      Spring, Summer, and Fall. Although all the patients had severe eosinophilic
      esophagitis, the intensity of esophageal eosinophilia was less in Winter than in
      Summer or Fall, but not Spring, seasons. CONCLUSIONS: A seasonal variation was
      noted with Winter, a season of low outdoor allergens, having the fewest number of
      newly diagnosed AEE patients.

PMID- 17450025
TI  - Bougienage versus endoscopy for esophageal coin removal in children.
AB  - BACKGROUND: Foreign body ingestion is a common pediatric problem. Coins are by
      far the most common ingested foreign bodies. When ingested coins become lodged in
      the esophagus, they may cause serious complications if they are not removed in a
      timely manner. Endoscopic removal is the preferred treatment in many pediatric
      centers as its safety and effectiveness are well established. OBJECTIVES: We
      performed this study to evaluate safety and effectiveness of an alternative
      method of managing esophageal coins, using bougienage technique. METHODS:
      Previously healthy children presenting to the local emergency room with
      uncomplicated, witnessed coin ingestion of less than 24 hours duration were
      prospectively recruited with an intent-to-treat analysis. A single oral passage
      of a Hurst bougie dilator was performed by a gastroenterologist to dislodge the
      esophageal coin into the stomach. If bougienage was successful (x-ray showing
      coin in the stomach), patients were discharged and instructions were given for
      monitoring stools until passage of the coin through anus was confirmed. If
      bougienage was unsuccessful, the child developed symptoms at any time or if a
      coin remained intragastric for 4 weeks, endoscopic removal was planned. Children
      whose parents declined to participate in the bougienage treatment received the
      standard endoscopic removal and their hospital records were used as controls.
      RESULTS: A total of 10 children were enrolled in this study, with a mean age of
      3.2 years (11 mo to 10 y), 6 boys and 4 girls. All received little or no
      sedation. Nine children (90%) were successfully treated using bougienage, all of
      whom spontaneously passed the ingested coins, with a mean duration of 2.6 days (1
      to 7 d) without subsequent intervention. A single case failed bougienage and
      underwent endoscopic removal. Three children declined bougienage treatment and
      underwent endoscopic removal. There were no reported minor or major adverse
      events with any of our cases. The mean health care cost for the hospital visit
      for bougienage treatment was $1210, compared with $3100 for the endoscopic
      removal (P<0.001). Furthermore, the mean time spent in the hospital from
      diagnosis to discharge was 2 hours for bougienage-treated patients compared with
      8 hours for endoscopic treatment (P<0.001). CONCLUSIONS: Bougienage of impacted
      esophageal coins is an effective, safe, and more economic treatment modality for
      selected pediatric patients with uncomplicated coin ingestion. This simple
      technique may provide a valuable tool to emergency room physicians or primary
      care doctors especially when endoscopy is not readily available.

PMID- 17450026
TI  - Prevalence of GERD symptoms in a representative Israeli adult population.
AB  - The prevalence of gastroesophageal reflux disease (GERD) symptoms in the general
      population is lower in Asian than Western countries. Data are lacking for
      countries in the Middle East. The aim of the study was to determine the
      prevalence and severity of GERD symptoms among Israeli Jews. A questionnaire
      including 8 specific questions for GERD symptoms was administered by telephone
      interview to a representative sample of the population. One thousand two hundred
      twenty-one of 1839 individuals were successfully contacted and 981 had valid,
      complete data. The mean age was 45.0 years and 55% were females. Over the
      previous year 34.8% of the respondents reported suffering any GERD symptom. Of
      these 11.6% reported retrosternal burning, 11.7% retrosternal pain, 19.0% an acid
      taste in the mouth, and 17.5% reflux of gastric content. In all, 6.5%, 5.2%,
      10.4%, and 7.9%, respectively, suffered these symptoms at least once a week, and
      2.0%, 1.8%, 2.4%, and 2.3%, respectively, defined their symptoms as frequent and
      severe. Male sex (P=0.01) and a functional lower gastrointestinal (GI) disorder
      (P<0.0001) contributed significantly to the severity of upper GI reflux-like
      symptoms. In conclusion, GERD symptoms are common among Israeli Jews. The
      symptoms are generally of mild-to-moderate severity and are significantly
      associated with lower functional GI disorders.

PMID- 17450027
TI  - Safety of endoscopy after myocardial infarction based on cardiovascular risk
      categories: a retrospective analysis of 135 patients at a tertiary referral
      medical center.
AB  - GOALS: To establish the safety of endoscopic procedures performed in patients
      with recent myocardial infarction (MI) based upon specific cardiac risk
      categories. BACKGROUND: There are no specific guidelines that dictate when to
      perform endoscopy in patients after recent MI, as this population may be at
      increased risk for cardiopulmonary complications at the time of endoscopy. STUDY:
      Retrospective analysis of data collected over 48 months on 135 patients who
      experienced a MI and within the next 30 days had an endoscopic procedure
      performed. Data on chronology of complications and certain cardiac risk
      categories were collected and analyzed. RESULTS: There was early termination of
      endoscopic procedures for a major cardiopulmonary complication in 2 of 135
      patients (1.5%). The complications occurred on hospital day 0 postMI. Performance
      of endoscopic procedures on the day of the MI was found to be a risk factor for a
      procedure-related complication (P=0.02). ST segment elevation myocardial
      infarction was seen in 19 patients (16.0%), severely depressed ejection fraction
      in 30 patients (22.2%), and troponin-I peak greater than 1.6 ng/mL in 96 patients
      (71.0%). No statistically significant increased risk of endoscopy was found in
      these subsets of patients (P=0.99). CONCLUSIONS: Endoscopic procedures can be
      safely performed early post-MI without imparting a significant cardiopulmonary
      risk. Timing of endoscopy increases risk of complications, but evidence of
      significant recent cardiac damage as demonstrated by ST segment elevation,
      depressed left ventricular ejection fraction, or troponin-I peak greater than 1.6
      ng/mL does not increase risk of cardiopulmonary complication.

PMID- 17450028
TI  - Prevalence of endoscopically identified heterotopic gastric mucosa in the
      proximal esophagus: endoscopist dependent?
AB  - GOALS: The aim of this study is to determine the prevalence of heterotopic
      gastric mucosa in the proximal esophagus (HGMPE) and whether thorough endoscopic
      search may influence such prevalence. BACKGROUND: Heterotopic gastric mucosa in
      the esophagus (sometimes known as inlet patch) refers to a discrete area of
      gastric mucosa, with a spherical or ellipsoid configuration, that is typically
      located in the proximal esophagus. The prevalence of endoscopically diagnosed
      HGMPE varies from 0.1% to 10%. Endoscopic detection may be difficult as HGMPE is
      often located at or just below the upper esophageal sphincter. It might be
      associated with severe complications such as bleeding, perforation, fistula, and
      stricture formation, in addition to the development of adenocarcinoma. STUDY:
      During a 2-year period, 455 consecutive patients with various gastrointestinal
      complaints underwent esophagogastroduodenoscopy by a single endoscopist (group
      1). This endoscopist paid special attention to detecting HGMPE by thoroughly
      examining the proximal esophagus upon withdrawal of the endoscope. During the
      same period of time, endoscopy reports of 472 patients who underwent
      esophagogastroduodenoscopy in the same hospital by 3 other endoscopists were
      retrospectively reviewed (group 2). These endoscopists were aware of the
      existence of the HGMPE and reported that the presence of HGMPE would be included
      as an endoscopic finding in their reports. RESULTS: In the first group, HGMPE was
      identified in 12 out of 455 patients (2.6%). Whereas in the second group, only 2
      out of 472 patients (0.4%) had reports identifying HGMPE (P<0.01). CONCLUSIONS:
      Endoscopic detection of HGMPE is influenced by the endoscopist's thorough search
      of this entity, and thus, more time devoted to such a search may lead to higher
      detection rates.

PMID- 17450029
TI  - Resection area of 15 mm as dividing line for choosing strip biopsy or endoscopic
      submucosal dissection for mucosal gastric neoplasm.
AB  - BACKGROUND: Endoscopic mucosal resection (EMR) is effective treatment for mucosal
      gastric neoplasm. Endoscopic submucosal dissection (ESD), a novel EMR method, has
      been reported to enable en bloc resection more frequently than conventional EMR
      methods such as strip biopsy (SB). However, ESD requires more time than SB. A
      small lesion can be resected en bloc and effectively treated with SB. GOAL: To
      evaluate using a 15 mm resection area as the dividing line between SB and ESD
      prospectively. STUDY: SB was applied for resection area less than 15 mm (SB
      group) and ESD for 15 mm or larger resection (ESD group). We compared
      characteristics of lesions and outcomes of EMR between the 2 groups. RESULTS:
      Ninety lesions were prospectively assigned to SB group (36 lesions) and ESD group
      (54 lesions). The average neoplasm size was 9.0+/-3.9 mm in the SB group and
      19.1+/-11.3 mm in the ESD group (P<0.01). The average resection time was 11.7+/
      5.8 minutes in the SB group and 128.9+/-102.8 minutes in the ESD group (P<0.01).
      The complete resection rate was 91.6% in the SB group and 83.3% in the ESD group
      (P=0.25). The complication rate was not significantly different between SB group
      and ESD group (11.1% vs. 16.7%, P=0.12). During follow-up (median 23+/-5 mo), 1
      patient in each group, who had piecemeal resection at original EMR had recurrent
      neoplasm. CONCLUSIONS: Gastric mucosal neoplasms which require only small (<15
      mm) resection can be treated with SB, as effectively as with ESD.

PMID- 17450030
TI  - Relation among plasma ghrelin level, gastric emptying, and psychologic condition
      in patients with functional dyspepsia.
AB  - BACKGROUND AND GOALS: Neurohormonal factors might play a role in the pathogenesis
      of functional dyspepsia (FD). However, the role of ghrelin, a gastrointestinal
      hormone that stimulates gastric motility, in FD is not yet clearly defined. The
      present study was designed to investigate plasma ghrelin levels and their
      relation with gastric emptying and psychologic status in FD. METHODS: Sixteen
      patients with FD of the dysmotility type and 19 healthy controls were enrolled in
      the study. Plasma active and desacyl ghrelin concentrations before and after test
      meal were measured by enzyme-linked immunosorbent assay. Gastric emptying and
      psychologic condition were studied using C acetate breath test and
      questionnaires, respectively. RESULTS: Gastric emptying was significantly
      prolonged in patients with FD compared with controls. Fasting desacyl and total
      ghrelin levels were significantly lower in FD patients than in controls, but
      fasting active ghrelin levels and postprandial levels of ghrelin in both forms
      were similar between the 2 groups. Fasting total ghrelin levels in FD patients
      did not differ from the postprandial levels, in contrast to what was found for
      controls. There was no significant association among gastric emptying, plasma
      ghrelin levels, and psychologic factors in FD patients. CONCLUSIONS: Total
      secretory ability or metabolic condition of ghrelin may be altered in patients
      with FD. This seems to play a role in the pathophysiology of dysmotility type FD,
      independent of delayed gastric emptying or psychologic disorders.

PMID- 17450031
TI  - Prevalence and impact of diarrhea on health-related quality of life in HIV
      infected patients in the era of highly active antiretroviral therapy.
AB  - OBJECTIVES: Before the introduction of highly active antiretroviral therapy
      (HAART), the majority of HIV-infected patients experienced diarrhea. The aims of
      this study were to compare the prevalence of diarrhea among HIV-infected and
      uninfected patients in the HAART era, and to evaluate the impact of diarrhea on
      health-related quality of life (HRQOL). METHODS: Diarrheal symptoms experienced
      by 163 consecutive HIV-infected patients and 253 HIV-seronegative control
      subjects were ascertained using a validated questionnaire. The HRQOL of these
      patients was assessed using the Medical Outcomes Study (MOS) SF-36 and MOS-HIV
      Health surveys. RESULTS: Among the 163 HIV-infected patients, the median CD4 cell
      count was 370 cells/mm and 150 individuals were taking HAART. Significantly, more
      HIV-infected subjects reported having 3 or more bowel movements daily within the
      past 7 days than did HIV-seronegative subjects (28.2% vs. 7.1%, P<0.001), even
      after adjusting for potential confounding variables (odds ratios=6.65; 95%
      confidence intervals, 3.36-13.17). In addition, diarrhea was significantly more
      common in HIV-infected patients than in control subjects when assessed by several
      other criteria. HIV-infected patients reported significantly worse HRQOL across
      all domains of the MOS SF-36 as compared with control subjects. Among HIV
      infected patients, individuals with diarrhea had significantly worse HRQOL in
      nearly all domains of the MOS-HIV as compared with those without diarrhea.
      CONCLUSIONS: Diarrhea remains an important clinical problem in HIV-infected
      patients and is associated with significant impairments in HRQOL. It is important
      that healthcare providers specifically evaluate their HIV-infected patients for
      diarrhea so that these symptoms may be optimally managed.

PMID- 17450032
TI  - Diversion of the fecal stream resolves ulcerative colitis complicating chronic
      granulomatous disease in an adult patient.
AB  - Chronic granulomatous disease (CGD) is a primary phagocytic disorder
      characterized by greatly increased susceptibility to severe bacterial and fungal
      infections. Patients with CGD may have gastrointestinal manifestations, commonly
      colitis, usually mimicking Crohn disease. We report an adult case, the second in
      literature, of CGD with severe colitis displaying histologic features of
      ulcerative colitis. The patient had a prompt improvement (continuing up to more
      than 5 y of follow-up) of the clinical picture after ileostomy and fecal
      diversion.

PMID- 17450033
TI  - Clinical epidemiology of primary biliary cirrhosis: incidence, prevalence, and
      impact of therapy.
AB  - Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease of unknown
      etiology. It is typically characterized by a trio of criteria including
      cholestatic liver biochemistry tests for at least 6 month's duration, the
      presence of a positive serum antimitochondrial antibody, and histologic findings
      from liver biopsy that are compatible or diagnostic with PBC. Although no
      unifying mechanism of action has been described to explain the pathogenesis of
      PBC to date, the natural history of this condition is greatly influenced by
      several known and unknown risk factors. In turn, a number of publications have
      focused on describing the burden of disease and prognosis in patients with PBC,
      This review article will summarize the descriptive epidemiology of PBC including
      new insights on risk factors, prognosis, and the effect of medical therapy in
      contemporary patients.

PMID- 17450034
TI  - Laboratory diagnosis and nonoperative management of biliary complications in
      living donor liver transplant patients.
AB  - BACKGROUND: Biliary complications associated with living donor liver
      transplantation (LDLT) remain a major problem. Information regarding biochemical
      abnormalities helpful for the diagnosis and the nonoperative management of such
      complications are limited. METHODS: Adult patients who underwent LDLT were
      retrospectively studied for biliary complications. Clinical findings and
      laboratory studies, that is, serum bilirubin, alkaline phosphatase, alanine
      aminotransferase, aspartate aminotransferase were evaluated. Diagnostic
      percutaneous transhepatic cholangiogram or endoscopic retrograde cholangiogram
      followed by therapeutic interventions such as endoscopic sphincterotomy, stone
      extraction, balloon dilation, or stent placement were done as indicated. Follow
      up data on clinical and biochemical outcomes were assessed. RESULTS: Among the
      first 29 patients who underwent LDLT, 7 patients (24%) developed biliary
      complications. Nonoperative treatment was undertaken through endoscopic
      retrograde cholangiogram in 4 cases, percutaneous transhepatic cholangiogram in 3
      cases with a successful clinical outcome in 6 cases (84%). All patients with
      biliary stricture had a bilirubin level >1.5 mg/dL with 100% sensitivity.
      CONCLUSIONS: A number of patients developed biliary complications after LDLT.
      Nonoperative treatments were successful in most patients. Elevated serum
      bilirubin level may be helpful in the diagnosis of biliary stricture complicating
      LDLT.

PMID- 17450035
TI  - Postgastrectomy development or accentuation of focal fatty change in segment IV
      of the liver: correlation with the presence of aberrant venous branches of the
      parabiliary venous plexus.
AB  - BACKGROUND: Focal fatty change in segment IV (S4) of the liver is occasionally a
      diagnostic dilemma in the postoperative follow-up of gastric cancer patients.
      GOAL: To determine whether development of focal fatty change in S4 is related to
      the presence of aberrant venous branches of the parabiliary venous plexus (PBP).
      STUDY: Two hundred seventy-six patients with gastrectomy who had been imaged by
      thin-slice preoperative computed tomography (CT) and at least one postoperative
      CT, and had no apparent liver masses were retrospectively analyzed. Preoperative
      CT were evaluated for the presence of aberrant venous branches of PBP entering
      S4. Serial postoperative CTs were evaluated for any interval change in the
      appearance of S4 of the liver. RESULTS: There were 6 patients out of 276 (2%) in
      whom focal fatty liver developed or accentuated after the surgery. In 5 out of
      the 6, preoperative CT demonstrated aberrant branches of PBP; 3 of these were
      suggested to be aberrant right gastric veins, and the etiologies were not
      determined in 2. In 1 case, no definite aberrant vessel was seen. Aberrant
      vessels were found in none of the remaining 270 patients. The incidence of
      aberrant vessels was significantly higher in patients who developed postoperative
      radiologic change in S4 than in those who did not (P<0.0001). CONCLUSIONS:
      Development or accentuation of focal fatty liver in S4 of the liver was observed
      in 2% of postgastrectomy patients and was closely related to the presence of
      aberrant venous branches of PBP.

PMID- 17450036
TI  - Hepatic steatosis has no impact on the outcome of treatment in patients with
      chronic hepatitis B infection.
AB  - BACKGROUND: Hepatic steatosis, as a predictive factor in treatment outcome, was
      not investigated in chronic hepatitis B (CHB). The aim of this retrospective
      analysis is to determine possible relationships between hepatic steatosis and
      treatment response in patients with CHB. METHODS: One hundred forty patients with
      CHB [42 hepatitis B e antigen (HBeAg)-positive, 98 HBeAg-negative] were analyzed.
      Seventy-eight patients (55.7%) received pegylated interferon alpha 2a 180 mug/wk
      subcutaneously and 62 patients (44.3%) received pegylated interferon alpha 2a 180
      mug/wk plus lamivudine 100 mg/d combination therapy. RESULTS: The presence of
      steatosis was associated with increased body mass index and hyperlipidemia. The
      sustained virologic response (SVR) rates in HBeAg-negative patients were 36.2%
      and 31.5% in patients with and without steatosis, respectively (P>0.05). The SVR
      rates in HBeAg-positive patients were 39.6% and 33.3% in patients with and
      without steatosis, respectively (P>0.05). The prevalence of hepatic steatosis did
      not significantly affect the outcome of treatments in both groups. In pegylated
      interferon monotherapy group (group 1), SVR was 18/78 (23%) and in the pegylated
      interferon plus lamivudine combination group (group 2) SVR was 16/62 (26%),
      (P>0.05, NS). The independent factors affecting the treatment outcome were higher
      baseline alanine aminotransferase level and lower baseline viral load.
      CONCLUSIONS: The prevalence of steatosis is a common finding in CHB infection;
      however, it is not associated with viral load and treatment outcome.

PMID- 17450037
TI  - Replacement of hepatitis C virus genotype 1b by genotype 2 over a 10-year period
      in Venezuela.
AB  - BACKGROUND: Changes in hepatitis C virus (HCV) genotype distribution with time
      have been reported in several countries. GOALS: To explore eventual changes in
      HCV genotype distribution in Venezuela over a 10 years period. STUDY: HCV
      genotype was determined by direct sequencing of the 5' noncoding region, in 236
      isolates circulating in patients treated during years 2005 to 2006. Genotype
      distribution was compared with the one observed in 43 patients followed during
      years 1994 to 1996. RESULTS: The prevalence HCV genotype 1 and 2 was 70% and 26%,
      respectively, in patients followed during years 1994 to 1996. The frequency of
      genotype 2 was significantly increased to 41% (P=0.04) in patients treated during
      years 2005 to 2006. A significant reduction in HCV genotype 1b prevalence (48% to
      27%, P=0.01) was also observed after this 10 years period, whereas the prevalence
      of HCV genotype 1a did not change over time (22% vs. 27%, NS). Transfusion was
      more significantly associated with infection with HCV genotype 1b than with other
      genotypes (52% vs. 20%, P=0.002). CONCLUSIONS: HCV subtype 1b seems to have been
      displaced by HCV genotype 2 in a relatively short period, without increase in the
      frequency of genotype 3. The low frequency of HCV genotype 3 in Venezuela might
      be due to the fact that intravenous drug use in Venezuela is less common than in
      other countries. The implementation of anti-HCV testing in blood banks since 1994
      in Venezuela, might have contributed to the reduction in the frequency HCV
      genotype 1b infection.

PMID- 17450038
TI  - The etiologic distribution of thrombophilic factors in chronic portal vein
      thrombosis.
AB  - GOALS: We aimed to prospectively investigate the full etiologic contributors to
      portal vein thrombosis. BACKGROUND: Portal vein thrombosis in the absence of
      liver disease is a rare cause of portal hypertension with a different clinical
      course and management strategy. The etiologic distribution of this interesting
      clinical picture is important as far as diagnostic and management issues are
      concerned. STUDY: After the application of exclusion criteria, 59 patients were
      included in the study who had normal liver functions, normal liver histology and
      studied the thrombophilia factors of both acquired factors and congenital factors
      like protein C, protein S, antithrombin levels with the mutations. RESULTS: In
      all, 23.7% of the patients were found to have acquired thrombophilia factors like
      myeloproliferative disorders and cyst hydatid disease, whereas 22.1% of the
      patient population was found to harbor no identifiable cause of thrombophilia,
      which we termed as idiopathic. One or more causes of thrombophilia were
      identified in 46 patients. There were 27 patients with protein C deficiency, 18
      patients with protein S deficiency. The antithrombin deficiency was found in 17
      patients. The factor V Leiden mutation was found in 7 patients. There was 1
      patient with homozygote mutation, whereas the remaining 6 patients were
      heterozygotes. There were 3 patients with prothrombin mutation who were
      heterozygote for this mutation. CONCLUSIONS: Complete investigation of
      thrombophilia is crucial to delineate the outline of thrombophilic risk factors
      to estimate the rethrombosis risk and for further management concerns.

PMID- 17450039
TI  - Safety of Erlangen precut papillotomy: an analysis of 1044 consecutive ERCP
      examinations in a single institution.
AB  - GOALS AND BACKGROUND: There is controversy about the ideal utilization of precut
      papillotomy in endoscopic retrograde cholangiopancreatography examinations.
      Almost all reports in the literature concentrate on needle knife precut
      papillotomy, reporting a wide range of complications. We have used Erlangen
      precut papillotomy in our institution and our aim was to compare the safety of
      Erlangen precut papillotomy to standard free cannulation technique. The influence
      of precutting on the deep biliary cannulation rate was also recorded. STUDY: Over
      a period of 48 months a total of 602 out of 1044 consecutive endoscopic
      retrograde cholangiopancreatography examinations fulfilled the inclusion
      criteria. Patients with an intact papilla who required biliary cannulation were
      screened. The cohort was divided into a nonprecut group (n=481) and a precut
      group (n=121). The standard technique included free biliary cannulation with a
      tapered-tip cannula. An Erlangen type papillotome was used for precutting.
      Complications, success rate of cannulation, and hyperamylasemia were recorded.
      RESULTS: Complication rates were similar in the 2 groups (nonprecut 7.1% vs.
      precut 8.3%, P=0.7). Hyperamylasemia was more common in the precut group (13.3%
      vs. 31.3%, P<0.001). The final deep biliary cannulation rate after precut
      papillotomy in cases with problematic cannulation was 98.2%. CONCLUSIONS:
      Erlangen precut papillotomy results in a high deep biliary cannulation rate with
      no increased risk of complications when compared to cannulation using standard
      techniques.

PMID- 17450041
TI  - The value of IL-6 in predicting the severity of acute pancreatitis.

PMID- 17450042
TI  - Cricopharangeal webs and carcinoma esophagus.

PMID- 17450043
TI  - Novel use of endoscopic ultrasound to diagnose aortoenteric fistula.

PMID- 17450044
TI  - Kleine-Levin syndrome mimicking mania.

PMID- 17450045
TI  - Primary supervision.

PMID- 17450046
TI  - Risperidone augmentation for treatment-resistant aggression in attention
      deficit/hyperactivity disorder: a placebo-controlled pilot study.
AB  - OBJECTIVE: To evaluate the effects of risperidone augmentation for treatment
      resistant aggression in children with attention-deficit/hyperactivity disorder
      (ADHD). METHOD: Twenty-five children (ages 7-12 years) with attention
      deficit/hyperactivity disorder (ADHD) and significant aggressive behaviors were
      randomized to risperidone or placebo for 4 weeks for this double-blind study.
      Subjects were already in treatment with a constant dose of psychostimulant
      medication. The primary efficacy measure was change from baseline in the
      Children's Aggression Scale-Parent (CAS-P) and -Teacher (CAS-T) total scores.
      RESULTS: The mean risperidone dose at endpoint was 1.08 mg/day. For the CAS-P
      total score, a significant difference was found (chi(1)(2) = 4.30, p < .05) with
      100% of risperidone subjects improving by more than 30% from baseline to
      endpoint, whereas only 77% of the placebo group reported a similar response. No
      differences were found on the CAS-T total score. For the CAS-P and CAS-T, no
      significant interaction was found between treatment group and time. Rates of
      adverse events did not differ significantly between groups. CONCLUSIONS:
      Risperidone treatment appears to be well tolerated and modestly effective when
      used in combination with psychostimulants for treatment-resistant aggression in
      children with ADHD.

PMID- 17450047
TI  - Effect of two different methods of initiating atomoxetine on the adverse event
      profile of atomoxetine.
AB  - OBJECTIVE: To compare the effects of two different methods for initiating
      atomoxetine in terms of the incidence of early adverse events. METHOD: Data on
      atomoxetine treatment-emergent adverse events in youths, ages 6 to 18 years, were
      analyzed from five randomized, double-blind, placebo-controlled, acute-phase
      studies. Two studies involve once-daily dosing and titration to 1.2 mg/kg/day
      over 3 days (fast/once daily, n = 234) and three involve twice-daily dosing and
      titration to a dose of 1.2 mg/kg/day over at least 2 weeks (slow/twice daily, n =
      213). RESULTS: During the first 2 weeks of treatment, fast/once daily titration
      patients showed higher rates of spontaneously reported adverse events than
      patients in the slow/twice daily titration group. This included decreased
      appetite (14.3% versus 8.0%, p = .036) and somnolence (14.3% versus 4.2%, p <
      .001). Patients in the slow/twice daily group showed higher rates of headache
      (7.4% versus 16.9%, p = .003). Analysis of the studies' overall acute treatment
      phases revealed significantly higher rates in the fast/once daily group only for
      somnolence. No significant differences were seen in completion rates or reasons
      for discontinuation. CONCLUSIONS: When starting atomoxetine, the risk of adverse
      events within the first few weeks of treatment may be lower if patients are dosed
      twice daily and titrated to the 1.2 mg/kg/day total daily dose over the first
      week.

PMID- 17450048
TI  - A manual-based intervention to address clinical crises and retain patients in the
      Treatment of Adolescents With Depression Study (TADS).
AB  - OBJECTIVE: To describe a manual-based intervention to address clinical crises and
      retain participants in the Treatment for Adolescents With Depression Study
      (TADS). METHOD: The use of adjunct services for attrition prevention (ASAP) is
      described for adolescents (ages 12-17 years) during the 12-week acute treatment
      in TADS, from 2000 to 2003. Logistic regression, controlling for site, was used
      to predict use. RESULTS: Of 439 enrolled participants, 17.8% (n = 78) used ASAP
      primarily for suicidality or worsening of depression. Of these, 46.2% continued
      in their assigned treatment through week 12, 47.4% received out-of-protocol
      treatment but continued participating in assessments, and 10.3% withdrew consent,
      including 3 who terminated treatment and withdrew consent on the same date. ASAP
      use did not differ between treatments (p =.97) and typically occurred early in
      treatment. At the end of the 12 weeks, 37.2% of participants using ASAP remained
      in their assigned treatment, although 80.8% continued participating in
      assessments. ASAP was associated with, at baseline, a higher severity of
      depression (p <.01), substance use (p <.01), and precontemplation level of change
      (p <.02). CONCLUSIONS: ASAP may be useful to retain adolescent participants and
      as a safety intervention in placebo-controlled trials. In clinical practice ASAP
      like procedures may be useful to encourage adherence in patients engaging in long
      term treatment. Clinical trial registration information-URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00006286.

PMID- 17450049
TI  - Time reproduction in children with ADHD and their nonaffected siblings.
AB  - OBJECTIVE: Time reproduction is deficient in children with attention
      deficit/hyperactivity disorder (ADHD). Whether this deficit is familial and could
      therefore serve as a candidate endophenotype has not been previously
      investigated. It is unknown whether timing deficits are also measurable in
      adolescent children with ADHD and nonaffected siblings. METHOD: These issues were
      investigated in 226 children with ADHD, 188 nonaffected siblings, and 162 normal
      controls ages 5 to 19. Children participated in a visual and auditory time
      reproduction task. They reproduced interval lengths of 4, 8, 12, 16, and 20
      seconds. RESULTS: Children with ADHD and their nonaffected siblings were less
      precise than controls, particularly when task difficulty was systematically
      increased. Time reproduction skills were familial. Time reproduction deficits
      were more pronounced in younger children with ADHD than in older children.
      Children with ADHD could be clearly dissociated from control children until the
      age of 9. After this age, group differences were somewhat attenuated, but were
      still present. Differences between nonaffected siblings and controls were
      constant across the age range studied. Deficits were unaffected by modality.
      CONCLUSIONS: Time reproduction may serve as a candidate endophenotype for ADHD,
      predominantly in younger children with (a genetic risk for) ADHD.

PMID- 17450050
TI  - ADHD symptoms in children with mild intellectual disability.
AB  - OBJECTIVES: To determine whether the nature and correlates of attention
      deficit/hyperactivity disorder (ADHD) symptoms are different in subjects with
      mild intellectual disability (ID) compared to subjects with average ability.
      METHOD: From a general population sample of 2,726 12- to 15-year-olds, a
      stratified subsample was selected to enrich for mild ID. A total of 192 subjects
      were included in the analyses. ADHD symptoms and other emotional/behavioral
      problems were measured with the parent and teacher Strengths and Difficulties
      Questionnaire and IQ with the WISC-III-UK), and social communication difficulties
      were assessed by a short version of the Social Communication Questionnaire and
      academic attainments by the Wechsler Quicktest. RESULTS: There was a negative
      linear relationship between ADHD symptoms and IQ (beta = -.087, p <.001). The
      relationship could not be explained by inappropriate rater expectations. Neither
      the profiles of ADHD symptoms nor the comorbidity with emotional/behavioral
      problems differed according to the presence of ID. When IQ was accounted for, the
      group difference in attainments was nonsignificant. CONCLUSIONS: ADHD symptoms
      are increased in people with ID. We found no evidence that this increase can by
      explained by inappropriate expectations or by confounding associations with other
      emotional/behavioral or cognitive problems.

PMID- 17450051
TI  - A 30-year prospective follow-up study of hyperactive boys with conduct problems:
      adult criminality.
AB  - OBJECTIVE: To compare the official arrest records for a large number of
      hyperactive boys (N = 179), most with conduct problems, and 75 control boys; to
      examine childhood IQ, socioeconomic status, and parent reports of childhood
      hyperactivity and conduct problems for their contribution to criminal behavior in
      adulthood; and to compare adult outcome for multimodality-treated (MMT) and drug
      treated-only (DTO) hyperactives. METHOD: We report on the official arrest history
      from early to mid- (18 to 38 years of age) adulthood in these 254 white subjects.
      RESULTS: Ninety one percent of subjects were followed up. California official
      arrest records were obtained on all of these subjects. Hyperactive subjects had
      significantly higher arrest, conviction, and incarceration rates compared with
      controls. Childhood antisocial behaviors, socioeconomic status, and IQ predicted
      adult criminality. Multimodality-treated boys with Hyperactive/ADHD (attention
      deficit/hyperactivity disorder) did not fare better than DTO boys with ADHD.
      CONCLUSIONS: Hyperactive/ADHD boys with conduct problems are at increased risk
      for adult criminality. Hyperactive boys without childhood conduct problems are
      not at increased risk for later criminality. An intensive 3-year MMT treatment of
      6- to 12-year-old hyperactive boys is insufficient to prevent later adult
      criminality.

PMID- 17450052
TI  - Comparison of the PSC-17 and alternative mental health screens in an at-risk
      primary care sample.
AB  - OBJECTIVE: To validate the 17-item version of the Pediatric Symptom Checklist
      (PSC-17) as a screen for common pediatric mental disorders in primary care.
      METHOD: Patients were 269 children and adolescents (8-15 years old) whose parents
      completed the PSC-17 in primary care waiting rooms. Children were later assessed
      using the Schedule for Affective Disorders and Schizophrenia for School-Age
      Children-Present and Lifetime version (K-SADS-PL). The PSC-17's subscales were
      compared with K-SADS-PL diagnoses and measures of anxiety, depression, general
      psychopathology, functioning, and impairment. RESULTS: In receiver operating
      characteristics analyses, the PSC-17 subscales performed as well as competing
      screens (Child Depression Inventory, the parent and child Screens for Child
      Anxiety-Related Disorders) and Child Behavior Checklist subscales (Aggressive,
      Anxious-Depressed, Attention, Externalizing, Internalizing, and Total) in
      predicting diagnoses of attention-deficit/hyperactivity disorder, externalizing
      disorders, and depression (area under the curve > or =0.80). The instrument was
      less successful with anxiety (area under the curve = 0.68). None of the screens
      were highly sensitive, many were insensitive, and all would have low positive
      predictive value in low-risk primary care populations. CONCLUSIONS: The PSC-17
      and its subscales are briefer than alternative questionnaires, but performed as
      well as those instruments in detecting common mental disorders in primary care.
      Continued research is needed to develop brief yet sensitive assessment
      instruments appropriate for primary care.

PMID- 17450053
TI  - A general population twin study of the CBCL/6-18 DSM-oriented scales.
AB  - OBJECTIVE: To explore the contributions of genetic and environmental influences
      to individual variation and covariation of the Child Behavior Checklist (CBCL)
      DSM-oriented scales (DOS) originally proposed by Achenbach and associates in
      2001. METHOD: A classic twin study of 398 twin pairs ages 8 to 17 years belonging
      to the population-based Italian Twin Registry, assessed by parents using the CBCL
      for Ages 6 to 18 (CBCL/6-18). RESULTS: Univariate analyses showed that compared
      with the classic CBCL/6-18 empirical subscales, the DOS have higher heritability
      (lowest 0.54 for Anxiety Problems, highest 0.71 for Conduct Problems) and simpler
      causal structure in that the phenotypic variance was satisfactorily explained by
      additive genetic and unique environmental factors only. Multivariate analyses
      showed that the causes of phenotypic correlation among the different DOS can be
      attributed to one common genetic factor and to two idiosyncratic environmental
      factors, each loading differently on the Internalizing (Anxiety and Affective
      Problems) and the Externalizing (Attention-Deficit/Hyperactivity, Oppositional
      Defiant, and Conduct Problems) CBCL/6-18 DOS. CONCLUSIONS: Several common risk
      factors of both genetic and environmental nature can simultaneously affect a
      child's proneness to develop the psychopathological signs and symptoms captured
      by the CBCL/6-18 DOS.

PMID- 17450054
TI  - Response and remission in adolescent mania: signal detection analyses of the
      young mania rating scale.
AB  - OBJECTIVE: The purpose of this study was to determine optimal criteria for
      defining response and remission in adolescents with acute mania. METHOD: Data
      were analyzed from three treatment studies of adolescents with acute mania (N =
      99). Trained raters completed the Young Mania Rating Scale (YMRS), and clinicians
      completed the Clinical Global Impressions Scale for Bipolar Disorder (CGI-BP)
      independent of YMRS ratings. For response, the percentages of reduction in YMRS
      scores from baseline to endpoint were compared with CGI-BP Mania Improvement
      scores. For remission, endpoint YMRS scores were compared with CGI-BP Mania
      Severity scores. Signal detection analyses were conducted to evaluate the
      efficiency of selected cutoffs associated with response and remission. RESULTS: A
      > or =55% reduction in YMRS scores from baseline to endpoint was the optimal
      cutoff defining response. An absolute endpoint YMRS score < or =12 was the
      optimal cutoff defining remission. CONCLUSIONS: The results of this signal
      detection analysis in adolescent mania suggest that current commonly used cutoffs
      to define response (> or =50% reduction) and remission (< or =12) may be
      appropriate with regard to efficiency. Studies with methods specifically tailored
      to evaluate and compare these rating scales and larger patient samples from
      multiple sites are needed to confirm these preliminary findings.

PMID- 17450055
TI  - An epidemiological and diagnostic study of Asperger syndrome according to four
      sets of diagnostic criteria.
AB  - OBJECTIVE: This study evaluated the diagnostic process and prevalence rates of
      Asperger syndrome (AS) according to the DSM-IV, ICD-10, and criteria developed by
      Gillberg and Gillberg and by Szatmari and colleagues and clarified confusion
      about AS. METHOD: An epidemiological study of 5,484 eight-year-old children in
      Finland, 4,422 (80.6%) of whom rated on the high-functioning Autism Spectrum
      Screening Questionnaire by parents and/or teacher, 125 of them screened and 110
      examined by using structured interview, semistructured observation, IQ
      measurement, school day observation, and patient records. Diagnoses were
      performed by following the DSM-IV, ICD-10, and criteria developed by Gillberg and
      Gillberg and by Szatmari and colleagues in detail. RESULTS: The prevalence rates
      per 1,000 were 2.5 according to the DSM-IV, 2.9 to ICD-10, 2.7 to Gillberg and
      Gillberg's criteria, and 1.6 to the criteria of Szatmari et al. CONCLUSIONS: The
      results emphasize the need to reconsider the diagnostic criteria of AS. The
      importance of multi-informant sources came up, and the need of several informants
      was highlighted, especially when diagnosing the broader pervasive developmental
      disorders.

PMID- 17450056
TI  - Understanding the common elements of evidence-based practice: misconceptions and
      clinical examples.

PMID- 17450057
TI  - Pharmacotherapy of aggression in a 9-year-old with ADHD.

PMID- 17450059
TI  - Treatment of vertebral osteomyelitis by radical debridement and stabilization
      using titanium mesh cages.
AB  - STUDY DESIGN: A retrospective clinical and radiologic evaluation of patients with
      vertebral osteomyelitis treated via radical debridement and stabilization using
      titanium mesh cages. OBJECTIVE: To assess the efficacy of titanium mesh cages in
      the treatment of active vertebral osteomyelitis. SUMMARY OF BACKGROUND DATA:
      Although titanium mesh cages have proven to be superior in trauma and tumor
      reconstructions, there are few reports regarding the use of titanium mesh cages
      in the presence of active pyogenic or tuberculotic vertebral osteomyelitis.
      METHODS: A total of 88 cases with vertebral osteomyelitis were operated on
      between January 2000 and December 2002. There were 2 craniocervical, 13 cervical,
      19 thoracic, 11 thoracolumbar, and 43 lumbar infections. The titanium mesh cages
      replaced 1 disc in 34 cases, 1 vertebral body in 28 cases, 2 vertebral bodies in
      23 cases, and 3 vertebral bodies in 3 cases. RESULTS: All patients showed a solid
      bony fusion without any recurrence of infection at latest follow-up. Changes in
      pain score, Frankel's classification, and blood parameters demonstrated a
      significant clinical improvement in all patients. The sagittal profile was
      restored. CONCLUSIONS: The use of titanium mesh cages in the treatment of
      vertebral osteomyelitis effectively reconstructs the anterior column, while
      adding stability and restoring the sagittal profile. There is no increase in the
      rate of recurrence or persistence of infection related to the implantation of
      titanium mesh cages.

PMID- 17450060
TI  - Key factors in back disability prevention: what influences the choice of
      priorities?
AB  - STUDY DESIGN: Survey, subgroup analysis, Q-analysis, and analysis of e-mail
      exchanges. OBJECTIVE: To assess what influences the choice of priorities for
      interventions to prevent back-related disability. SUMMARY OF BACKGROUND DATA:
      Back-related disability results from interaction of physical, psychological,
      occupational, and social factors. However, opinions differ on which factors
      should be targeted by interventions aimed at preventing disability. METHODS: A
      Delphi panel (14 researchers and 19 occupational health stakeholders) attempted
      to reach consensus about the relative impact and modifiability of 32 factors
      involved in back-related disability. Data gathered during the panel were analyzed
      using 4 methods: (1) a survey asking panel members what influenced their
      rankings, (2) subgroup analysis to compare differences in rankings according to
      members' backgrounds and affiliations, (3) Q-analysis to identify views shared by
      members, and (4) qualitative analysis of e-mail exchanges during the panel
      process. RESULTS: Besides research evidence about a factor, we found that the
      greatest influence was the personal experience of panel members, which included
      diverse views about the nature of back disability, expectations about how
      interventions would be implemented, the typical workers or patients seen by them,
      and their values and principles. The member's educational background and current
      affiliation played a lesser role in their choice of priorities. The choice of
      priorities was also influenced by difficulties in separating the impact of a
      factor from its modifiability, whether the panel member considered occupational
      or nonoccupational disability, and the intricate linkages between the factors.
      CONCLUSIONS: This study suggests the choice of priorities is primarily influenced
      by different views about disability and other components of personal experience.
      Secondary influences included process difficulties in making a choice. The
      person's background and affiliation had a weak association with the views and
      choice of priorities.

PMID- 17450061
TI  - An unusual case of penetrating injury to the spine resulting in cauda equina
      syndrome: case presentation and a review of the literature.
AB  - STUDY DESIGN: Case study. OBJECTIVE: We present an unusual case of cauda equina
      syndrome due to a penetrating injury in which the brake caliper of a motorcycle
      lodged in the lumbar canal of the operator of the vehicle after a road accident
      and provide a review of the literature on penetrating injury to the spine.
      SUMMARY OF BACKGROUND DATA: While the large majority of penetrating spinal
      injuries are due to gunshot wounds, penetrating injury to the spine causing cauda
      equina syndrome is rare. METHODS: We report the case of a 42-year-old man
      involved in a motorcycle accident in which the brake caliper penetrated the
      lumbar region and entered the lumbar canal through the interlaminar space between
      L2 and L3. He had a complete motor and sensory deficit in the lower extremities
      with absent rectal tone. The patient was taken urgently to the operating room and
      underwent removal of the foreign object and repair of a dural laceration. He was
      treated with a course of intravenous antibiotics. RESULTS: The wound healed
      without evidence for cerebrospinal fluid leakage or infection. The patient made a
      good neurologic recovery, becoming ambulatory with bowel and bladder continence
      at 5 months following the injury. CONCLUSIONS: Surgical removal of foreign object
      resulted in resolution of cauda equina syndrome injury.

PMID- 17450062
TI  - Total en bloc spondylectomy of C5 vertebra for chordoma.
AB  - STUDY DESIGN: En bloc resection of a chordoma of the C5 vertebra with wide
      surgical margins. OBJECTIVE: To present the surgical technique of total
      spondylectomy for a chordoma of the C5 vertebral body. SUMMARY OF BACKGROUND
      DATA: Malignant bone tumors require wide resection. Wide resection by total en
      bloc spondylectomy is difficult or not feasible for malignant vertebral tumors of
      the cervical spine due to the peculiar anatomic complexity of this region,
      including the vertebral arteries and the neural structures. There are no previous
      reports of en bloc resection of cervical spine tumors with wide surgical margins.
      METHODS: Using staged posterior and anterior approaches, a total en bloc
      spondylectomy and spine arthrodesis was performed. En bloc excision of a C5
      chordoma was achieved using a threadwire T-saw (Tomita and Kawahara, Kanazawa,
      Japan) with surgical margins free of tumor. The patient received postoperative
      adjuvant proton beam radiation therapy. RESULTS: The patient remains disease-free
      9 years after the operation. CONCLUSION: Total en bloc spondylectomy with wide
      surgical margins is feasible for malignant bone tumors of the cervical spine.

PMID- 17450063
TI  - Lumbar synovial joint hematoma in a patient on anticoagulation treatment.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To describe a case of spinal epidural
      hematoma arising from the synovial joint due to anticoagulation therapy. SUMMARY
      OF BACKGROUND DATA: Spontaneous spinal epidural hematoma is a rarity in the
      literature with a variety of etiologies. In 1 study, it was reported to originate
      from a synovial joint due to osteoarthritis of the joint. METHODS: A case of
      hematoma of the lumber synovial joint is presented. RESULTS: A 67-year-old man
      who was on anticoagulation therapy presented with progressive neurologic symptoms
      in the right lower limb. Magnetic resonance imaging scan revealed what was
      thought to be a L4-L5 synovial joint cyst. During surgery, it was proven to be an
      epidural hematoma originating from the synovial joint. Microscopic examination
      confirmed the diagnosis and excluded the possibility of spinal synovial cyst.
      After spinal decompression, neurologic symptoms improved completely in 2 weeks.
      CONCLUSIONS: This is the first report of a synovial cyst hematoma due to
      anticoagulation therapy. Its magnetic resonance imaging features can be similar
      to synovial cyst, especially when it is hemorrhagic. Spinal decompression was the
      definitive treatment.

PMID- 17450065
TI  - A randomized controlled trial evaluating the effects of new task chairs on
      shoulder and neck pain among sewing machine operators: the Los Angeles garment
      study.
AB  - STUDY DESIGN: This is a 4-month randomized controlled trial to evaluate the
      effect of chair design on neck/shoulder pain among sewing machine operators.
      OBJECTIVE: Determine whether a chair with a curved seat pan leads to improved
      changes in monthly neck/shoulder pain scores compared with a control
      intervention. SUMMARY OF BACKGROUND DATA: Sewing machine operators experience a
      high prevalence and severity of neck and shoulder pain in comparison to other
      working populations probably due to the sustained shoulder abduction and neck and
      upper back flexion required of the task. An adjustable height task chair that
      supports a forward sitting posture may reduce these posture-related risk factors
      and reduce neck/shoulder pain. MATERIALS AND METHODS: A total of 277 sewing
      machine operators with neck/shoulder pain were assigned to receive 1)
      miscellaneous items (control group), 2) a chair with a flat seat pan plus
      miscellaneous items, or 3) a chair with a curved seat pan plus miscellaneous
      items. Participants completed a monthly questionnaire assessing neck/shoulder
      pain severity. RESULTS: Based on estimates of pain score changes from a repeat
      measures linear regression, participants who received the flat seat chair
      experienced a decline in pain of 0.14 (95% confidence interval, 0.07-0.22) points
      per month compared with those in the control group, while those who received the
      curved seat experienced a decline of 0.34 (95% confidence interval, 0.28-0.41)
      points per month compared with those in the control group. These estimates did
      not change after adjustment for potential covariates. CONCLUSIONS: These findings
      demonstrate that an adjustable height task chair with a curved seat pan can
      reduce neck and shoulder pain severity among sewing machine operators.

PMID- 17450066
TI  - The efficiency of gabapentin therapy in patients with lumbar spinal stenosis.
AB  - STUDY DESIGN: Randomized controlled study. OBJECTIVES: To investigate the
      efficacy of treatment with gabapentin on the clinical symptoms and findings in
      patients with lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: LSS is a
      syndrome resulting from the narrowing of the lumbar nerve root canal, spinal
      canal, and intervertebral foramen, causing compression of the spinal cord. The
      most significant clinical symptom in patients with LSS is neurologic intermittent
      claudication (NIC). Gabapentin, which has been used in the treatment of
      neuropathic pain, may be effective in the treatment of symptoms associated with
      LSS. METHODS: Fifty-five patients with LSS, who had NIC as the primary complaint,
      were randomized into 2 groups. All patients were treated with therapeutic
      exercises, lumbosacral corset with steel bracing, and nonsteroidal anti
      inflammatory drugs. The treatment group received gabapentin orally in addition to
      the standard treatment. RESULTS: Gabapentin treatment resulted in an increase in
      the walking distance better than what was obtained with standard treatment (P =
      0.001). Gabapentin-treated patients also showed improvements in pain scores (P =
      0.006) and recovery of sensory deficit (P = 0.04), better than could be attained
      with the standard treatment. CONCLUSION: Based on the results of our pilot study,
      extensive clinical studies are warranted to investigate the role of gabapentin in
      the management of symptomatic LSS.

PMID- 17450067
TI  - Transplantation of preconditioned Schwann cells following hemisection spinal cord
      injury.
AB  - STUDY DESIGN: Chronically compressed sciatic nerve segments were transplanted to
      hemisected spinal cord injured rats. Histologic evaluation and behavior
      functional outcomes were tested after 6 weeks following surgery. OBJECTIVE: To
      evaluate the outcome of preconditioned peripheral nerves as a permissive
      environment in axonal regeneration of the injured spinal cord. SUMMARY OF
      BACKGROUND DATA: Schwann cells have been used to facilitate a permissive
      environment for the injured spinal cord to regenerate. Previous experiments have
      shown compressive mechanical stress to be important in stimulating the
      regenerative behavior of Schwann cells. Transplantation of highly permissive
      Schwann cell-enriched peripheral nerve grafts may enhance regeneration in spinal
      cord injury. METHODS: Adult Sprague-Dawley rats (n = 24) were used to create a
      hemisection injury of the spinal cord. At 1-week postinjury creation, the spinal
      cords were reexposed for all animals. Peripheral nerve grafts were obtained from
      rat sciatic nerve, either untreated or subjected to mechanical compression for 2
      weeks with nonconstrictive tubing. Transplantation of grafts was performed after
      a resection of the glial scar. Functional outcome was measured using the Basso,
      Beattie, Bresnahan Locomotor Rating Score and footprint analysis. Tract tracing
      of descending and ascending spinal cord tracts was performed at 6 weeks after
      surgery for histologic evaluation of axonal regeneration. RESULTS: Preconditioned
      transplants had significantly higher Basso, Beattie, Bresnahan Scores versus
      hemisection alone in the late postoperative period (P < 0.05). They also had
      significantly less foot exorotation and base of support when compared to
      nonconditioned transplants. Histologic analysis showed increased regeneration at
      lesional sites for preconditioned transplants versus control group (P < 0.05).
      CONCLUSIONS: Functional recovery after hemisection injury improved significantly
      in the late postoperative period with transplantation of preconditioned
      peripheral nerve. Preconditioned grafts also exhibit sustained axonal
      regeneration at and past the lesional site in histologic analysis. Further
      investigation with later time points is warranted.

PMID- 17450068
TI  - Neurophysiologic changes after preganglionic and postganglionic nerve-root
      constriction: an experimental study in the rat.
AB  - STUDY DESIGN: We investigated changes in spinal somatosensory-evoked potential
      (SSEP) and nerve action potential (NAP), correlated behavior, and associated
      pathologic observation in experimental radiculopathy. OBJECTIVES: To create a rat
      model of sacrococcygeal radiculopathy for determining the validity of SSEP and
      NAP. SUMMARY OF BACKGROUND DATA: We examined the diagnostic sensitivity and value
      of electrophysiologic tests for evaluating lumbosacral root disease conflict. An
      appropriate animal model can help verify the value of these tests. METHODS:
      Preganglionic lesion group rats were given 2 loose ligatures around the cauda
      equina at the sacrum, and postganglionic lesion group rats were given 2 loose
      ligatures on the conjunction of the sacrococcygeal nerve roots and the caudalis
      nerve after they had received a laminectomy. Control group rats received a sham
      operation. SSEPs and NAPs were recorded preligature and postligature, and 3 times
      after surgery. These electrophysiologic observations were compared and correlated
      with tail-flick reflex and histology. RESULTS: All experimental group rats
      developed thermal hyperalgesia on day 14, as indicated by a significant reduction
      in TFL (tail-flick latency), which continued for 3 months. Amplitude decreased
      significantly and latency increased significantly in all SSEP recordings
      immediately after the operation; these changes persisted for 3 months. There were
      no significant differences between the experimental groups, but there were
      significant differences between the control and experimental groups. NAP
      amplitude and latency from the caudalis nerves did not change in any group in the
      first 2 postoperative weeks. From the second postoperative week until the 3-month
      follow-up, amplitude was significantly decreased and latency prolonged in the
      postganglionic group but unchanged in the others. CONCLUSIONS: Both SSEP and NAP
      are useful for evaluating electrophysiologic changes after various
      radiculopathies. The data also suggest that the conductivity of the peripheral
      nerve (NAP) was affected by the postganglionic compression of the corresponding
      nerve root, but not by the preganglionic lesion.

PMID- 17450069
TI  - Hybrid testing of lumbar CHARITE discs versus fusions.
AB  - STUDY DESIGN: An in vitro human cadaveric biomechanical study. OBJECTIVES: To
      quantify effects on operated and other levels, including adjacent levels, due to
      CHARITE disc implantations versus simulated fusions, using follower load and the
      new hybrid test method in flexion-extension and bilateral torsion. SUMMARY OF
      BACKGROUND DATA: Spinal fusion has been associated with long-term accelerated
      degeneration at adjacent levels. As opposed to the fusion, artificial discs are
      designed to preserve motion and diminish the adjacent-level effects. METHODS:
      Five fresh human cadaveric lumbar specimens (T12-S1) underwent multidirectional
      testing in flexion-extension and bilateral torsion with 400 N follower load.
      Intact specimen total ranges of motion were determined with +/-10 Nm
      unconstrained pure moments. The intact range of motion was used as input for the
      hybrid tests of 5 constructs: 1) CHARITE disc at L5-S1; 2) fusion at L5-S1; 3)
      CHARITE discs at L4-L5 and L5-S1; 4) CHARITE disc at L4-L5 and fusion at L5-S1;
      and 5) 2-level fusion at L4-L5-S1. Using repeated-measures single factor analysis
      of variance and Bonferroni statistical tests (P < 0.05), intervertebral motion
      redistribution of each construct was compared with the intact. RESULTS: In
      flexion-extension, 1-level CHARITE disc preserved motion at the operated and
      other levels, while 2-level CHARITE showed some amount of other-level effects. In
      contrast, 1- and 2-level fusions increased other-level motions (average, 21.0%
      and 61.9%, respectively). In torsion, both 1- and 2-level discs preserved motions
      at all levels. The 2-level simulated fusion increased motions at proximal levels
      (22.9%), while the 1-level fusion produced no significant changes. CONCLUSIONS:
      In general, CHARITE discs preserved operated- and other-level motions. Fusion
      simulations affected motion redistribution at other levels, including adjacent
      levels.

PMID- 17450071
TI  - Development and validation of a finite element model of the occipito-atlantoaxial
      complex under physiologic loads.
AB  - STUDY DESIGN: Numerical techniques were used to study the occipito-atlantoaxial
      complex. OBJECTIVES: To improve previous upper cervical spine finite element
      models and validate both the range of motion (ROM) and neutral zone of the model.
      SUMMARY OF BACKGROUND DATA: Finite element modeling is an important tool for
      studying the cervical spine. It has been theorized that the neutral zone may be a
      more sensitive parameter of spinal instability than ROM. However, the authors
      know of no published results by far that have validated the neutral zone of an
      occipito-atlantoaxial finite element complex. METHODS: An anatomic detailed,
      nonlinear finite element model based on the Visible Human Male data set was
      developed in this study. ROM and the neutral zone were compared with published
      experimental data in the analysis of the motions of each vertebral level under
      physiologic static loadings to simulate the movements of upper cervical spine
      under axial rotation, flexion, extension, and lateral bending. In addition, the
      loads of each ligament were also recorded. RESULTS: The moment-rotation
      relationship predicted by this model was apparently nonlinear, and the largest
      rotation was predicted in horizontal plane, followed by median plane and coronal
      plane. The ligaments across the complex were generally lax, and, therefore, the
      complex exhibited large ROMs and high proportions of the neutral zone to ROM.
      CONCLUSIONS: The findings from the validation of this newly developed model
      coincide with the experimental studies so that its application helps contribute
      to a more comprehensive understanding of the biomechanics of the craniocervical
      region.

PMID- 17450072
TI  - Utility of flexion-extension radiographs in evaluating the degenerative cervical
      spine.
AB  - STUDY DESIGN: Retrospective cohort of 258 consecutive patients. OBJECTIVE: The
      purpose of this study is to determine the: (1) percentage of flexion-extension
      radiographs that revealed pathology not appreciated on neutral radiographs in the
      nontrauma population, and (2) frequency that these views led to a change in the
      management of these patients. SUMMARY OF BACKGROUND DATA: The utility of flexion
      extension radiographs in the evaluation of the spine trauma or preoperative
      patient is well accepted, but the role of dynamic radiographs in the degenerative
      population is not well defined. METHODS: Consecutive patients presenting with
      axial cervical, upper extremity radicular, or myelopathic symptoms underwent
      upright anteroposterior, neutral lateral, and flexion-extension lateral
      radiographs. Patients with recent trauma, rheumatoid arthritis, prior cervical
      fracture, prior cervical surgery, inadequate radiographs, or congenital anomalies
      were excluded. Three observers reviewed all radiographs after determining the
      best measurement method by a priori analysis of interobserver reliability.
      RESULTS: Listhesis was observed on 23 of the neutral lateral images; 6 of these
      were found to have changes between flexion and extension (2-4 mm). Two patients
      (1%) had spondylolisthesis on flexion-extension radiographs not visualized on
      neutral lateral radiographs. A subsequent review of these patients' charts
      revealed no change in management based on these findings. CONCLUSIONS: Cervical
      flexion-extension radiographs are a method of assessing potential instability. In
      the degenerative population studied here, 1% had spondylolisthesis noted only on
      the flexion-extension images, and 3% had a change in spondylolisthesis. None of
      these, however, led to a changes in clinical management. These data, in
      conjunction with the extra cost and radiation exposure associated with additional
      views, led us to no longer regard dynamic radiographs as a useful part of the
      initial imaging for the patient with degenerative cervical conditions.

PMID- 17450073
TI  - Clinical classification of patients with lumbar spinal stenosis based on their
      leg pain syndrome: its correlation with 2-year surgical outcome.
AB  - STUDY DESIGN: Prospective follow-up and retrospective review of 174 patients
      surgically treated for degenerative lumbar spinal stenosis. OBJECTIVE: To examine
      whether the type of leg pain syndrome associated with lumbar spinal stenosis is
      correlated with outcome. SUMMARY OF BACKGROUND DATA: Although classifying
      patients based on their leg pain syndrome is useful in planning surgical
      decompression, there is no validated method of classification and its prognostic
      significance remains unknown. METHODS: Based on the type of leg pain, the
      patients were classified into 2 groups: unilateral and bilateral. Improvement in
      functional status was evaluated using the Quebec Back Pain Disability Scale; the
      symptoms were rated on a visual analog scale and the change from baseline to 2
      year evaluation was noted. Associations between score changes and baseline
      variables were examined using multivariate analysis. RESULTS: The type of leg
      pain was independently associated with improvements in function and leg symptom
      scores but was not associated with improvement in the back pain score. After
      surgery, patients with unilateral leg pain had significantly greater improvements
      in function and leg symptoms than patients with bilateral leg pain. CONCLUSION:
      In patients undergoing surgery for degenerative lumbar spinal stenosis, the
      preoperative type of leg pain predicts function and leg symptom outcomes.

PMID- 17450074
TI  - Minimum 5-year follow-up surgical results of post-traumatic thoracic and lumbar
      kyphosis treated with anterior instrumentation: comparison of anterior plate and
      dual rod systems.
AB  - STUDY DESIGN: A retrospective follow-up study of post-traumatic thoracic and
      lumbar kyphosis after anterior instrumentation with anterior plate and dual rod
      systems. OBJECTIVE: To investigate the outcome of anterior vertebrectomy,
      anterior strut grafting, and anterior instrumentation in patients with > 30
      degrees sagittal contour deformity. SUMMARY OF BACKGROUND DATA: Post-traumatic
      kyphosis may lead to mechanical pain due to the impairment of physiologic
      sagittal contours as well as cosmetic complaints. METHODS: Forty patients with
      post-traumatic kyphosis were followed for a minimum of 5 years. Mean age was 44.7
      +/- 12.4 years (range, 18-65 years); 18 were female and 22 were male. All
      patients underwent anterior vertebrectomy and decompression; anterior fusion was
      carried out with costal or iliac ala grafts. Patients were randomly assigned into
      2 treatment groups: correction and internal fixation was performed by using
      either plate-screw (n = 20) or double rod-screw (n = 20). Patients were also
      evaluated clinically by using Pain and Functional Assessment Scale (PFA) and SRS
      22 questionnaire. RESULTS: Before surgery, the mean value for local sagittal
      contours was 51.4 degrees +/- 13.8 degrees; after surgery, it was reduced to 7.0
      degrees +/- 7.6 degrees, resulting in an 88.7% +/- 11.3% correction (P = 0.00).
      At the last follow-up visit, a mean correction loss of 1.4 degrees +/- 1.8
      degrees was found. A statistically significant improvement in local kyphosis
      angles and PFA scores was found after surgery and at the last visit. In 92.5% of
      the patients (n = 36), pain completely resolved; and in the remaining 3 patients,
      it is markedly reduced. Neurologic improvement was achieved in all of the 24
      patients with neural claudication and other neurologic findings. Solid fusion
      mass was obtained in all patients. The type of instrumentation system did not
      differ significantly in terms of kyphotic deformity correction rates, correction
      losses, PFA scores, and SRS-22 scores. Final PFA scores showed a statistically
      significant correlation with SRS-22 scores (r = -0.918, P < 0.01). Final pain,
      function, mental status, self image and satisfaction domain scores and total SRS
      22 score were > or = 4. The time from trauma to operation and the severity of
      kyphotic deformity were inversely correlated with postoperative correction rates.
      On the other hand, these 2 parameters were positively correlated with both final
      PFA and final SRS-22 scores (P < 0.01). CONCLUSIONS: In light of the present
      study's findings, we suggest that the technique of anterior decompression, strut
      grafting, and anterior instrumentation is an effective method for the treatment
      of post-traumatic kyphotic deformity and that the success of the technique
      depends on the time from trauma to operation and the severity of baseline
      deformity, regardless of the type of instrumentation.

PMID- 17450075
TI  - Clinical outcome of symptomatic unilateral stress injuries of the lumbar pars
      interarticularis.
AB  - STUDY DESIGN: A prospective case-series study. OBJECTIVE: To evaluate the results
      of nonoperative and operative treatment of symptomatic unilateral lumbar pars
      stress injuries or spondylolysis. SUMMARY OF BACKGROUND DATA: Most patients
      become asymptomatic following nonoperative treatment for unilateral lumbar pars
      stress injuries or spondylolysis. Surgery, however, is indicated when symptoms
      persist beyond a reasonable time affecting the quality of life in young patients,
      particularly the athletic population. METHODS: We treated 42 patients (31 male,
      11 female) with unilateral lumbar pars stress injuries or spondylolysis. Thirty
      two patients were actively involved in sports at various levels. Patients with a
      positive stress reaction on single photon emission computerized tomography
      imaging underwent a strict protocol of activity restriction, bracing, and
      physical therapy for 6 months. At the end of 6 months, patients who remained
      symptomatic underwent a computed tomography (CT) scan to confirm the persistence
      of a spondylolysis. Eight patients subsequently underwent a direct repair of the
      defect using the modified Buck's Technique. Baseline Oswestry Disability Index
      (ODI) and Short-Form-36 (SF-36) scores were compared with 2-year ODI and SF-36
      scores for all patients. RESULTS: Eight of nine fast bowlers in cricket were
      right-handed. The spondylolytic defect appeared on the left side of their lumbar
      spine. In the nonoperated group, the mean pretreatment ODI was 36 (SD = 10.5),
      improving to 6.2 (SD = 8.2) at 2 years. In SF-36 scores, the mean score for
      physical component of health (PCS) improved from 30.7 (SD = 3.2) to 53.5 (SD =
      6.5) (P < 0.001), and the mean score for the mental component of health (MCS)
      improved from 39 (SD = 4.1) and 56.5 (SD = 3.9) (P < 0.001) at 2 years. Twenty of
      32 patients resumed their sporting career within 6 months of onset of treatment,
      and a further 4 of 32 patients returned to sports within 1 year. The 8 patients
      who remained symptomatic at 6 months underwent a unilateral modified Buck's
      repair. The most common level of repair was L5 (n = 5). One patient with spina
      bifida and a right-sided L5 pars defect remained symptomatic following direct
      repair. The mean preoperative ODI was 39.4 (SD = 3.6), improving to 6.4 (SD =
      5.2) at the latest follow-up. The mean score of PCS (SF-36) improved from 29.6
      (SD = 4.4) to 49.2 (SD = 6.2) (P < 0.001), and the mean score of MCS (SF-36)
      improved from 38.7 (SD = 1.9) to 54.5 (SD = 6.4) (P < 0.001). CONCLUSIONS: The
      increased incidence of the unilateral lumbar pars stress injuries or frank defect
      on the contralateral side in a throwing sports, e.g., cricket (fast bowling), may
      be related to the hand dominance of the individual. Nonoperative treatment for
      patients with a unilateral lumbar pars stress injuries or spondylolysis resulted
      in a high rate of success, with 81% (34/42) of patients avoiding surgery. If
      symptoms persist beyond a reasonable period, i.e., 6 months, and reverse gantry
      CT scan confirms a nonhealing defect of the pars interarticularis, one may
      consider a unilateral direct repair of the defect with good functional outcome.
      Direct repair in patients with spina bifida at the same lumbar level as the
      unilateral defect may be complicated by nonunion.

PMID- 17450076
TI  - Revision and explantation strategies involving the CHARITE lumbar artificial disc
      replacement.
AB  - STUDY DESIGN: A large case series of anterior revision surgery in patients who
      had complications following lumbar total disc replacement with the CHARITE
      artificial disc. OBJECTIVES: To analyze and discuss the etiology of implant
      related complications and to present a strategy that can be applied to lumbar
      intervertebral disc prostheses in cases where anterior revision surgery is
      necessary. SUMMARY OF BACKGROUND DATA: This report represents the largest single
      site, consecutive case series reported in the literature of anterior revision
      surgery following lumbar disc arthroplasty. METHODS: A total of 18 patients are
      included in this study. All patients required an anterior revision procedure for
      repositioning or removal of the prosthesis. The mean time to revision was 6
      months (range, 9 days to 4 years). RESULTS: In 17 of 20 cases, implant removal
      was required and the patient was converted to a fusion. In 3 cases, primary
      revision of the CHARITE artificial disc was performed. Six revision cases were
      performed within the early postoperative period, defined as 7 to 14 days. All
      early cases were approached via reexploration of the original anterior midline
      retroperitoneal incision. Late revision was required in 14 cases, ranging from 3
      weeks to 4 years following initial arthroplasty. A variety of surgical approaches
      were used in late revisions, including the lateral transpsoas approach at L3-L4
      or L4-L5 (n = 5), expanded ipsilateral left retroperitoneal approach at L4-L5 (n
      = 2), contralateral right retroperitoneal approach at L5-S1 (n = 6), and
      transperitoneal approach (n = 1). Following 20 consecutive, anterior revision
      procedures, implant revision was successfully achieved in all cases. CONCLUSIONS:
      Total disc replacement implant revisions occur largely as a result of technical
      errors in positioning and sizing of the implant. In addition, adherence to strict
      patient selection criteria will eliminate many cases of implant failure. When
      necessary, anterior revision surgery can be performed safely when a strategic
      approach is used.

PMID- 17450077
TI  - CHARITE versus ProDisc: a comparative study of a minimum 3-year follow-up.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVES: To evaluate and compare clinical
      and radiologic outcomes of the CHARITE and ProDisc. SUMMARY OF BACKGROUND DATA:
      There is no clinical report comparing CHARITE and ProDisc. METHODS: Among a total
      of 61 patients who underwent total disc replacement, 57 patients followed more
      than 3 years were enrolled. The CHARITE was used in 33 patients and ProDisc in
      24. MRI follow-up was possible in 52 patients. Clinical and radiologic data
      including range of motion (ROM) and facet degeneration of the replaced segment,
      and degeneration of the disc at the adjacent level were evaluated. RESULTS: Mean
      percentage improvement of Oswestry Disability Index (ODI) score was 78.9% in the
      CHARITE group and 75.8% in ProDisc group. The mean improvement of the Visual
      Analogue Scale (VAS) pain score was 72% in the CHARITE and 74.2% in ProDisc.
      There was no statistical difference between 2 groups in improvement rates either
      of the ODI scores and VAS scores. Degradation of the facets was seen in 36.4% of
      the CHARITE and 32% of the ProDisc. Degradation of disc degeneration at the
      adjacent level above the index level was seen in 19.4% in the CHARITE and 28.6%
      in the ProDisc. The degradation rates of facet joints and disc at adjacent
      segment between the 2 groups were not significantly different. Segmental ROM of
      the replaced segments was well preserved, but ROM of L5-S1 of the ProDisc was
      significantly less than that of the CHARITE. CONCLUSIONS: While clinical outcomes
      of both CHARITE and ProDisc groups were fairly good, the facet joint of the index
      level and the disc at the adjacent level showed an aggravation of the
      degenerative process in a significant number of patients, regardless of the
      device used, raising concerns of possible late consequences of total disc
      replacement, especially regarding facet arthrosis and adjacent segment disease.

PMID- 17450078
TI  - Quantitative computed tomography-based predictions of vertebral strength in
      anterior bending.
AB  - STUDY DESIGN: This study examined the ability of QCT-based structural assessment
      techniques to predict vertebral strength in anterior bending. OBJECTIVE: The
      purpose of this study was to compare the abilities of QCT-based bone mineral
      density (BMD), mechanics of solids models (MOS), e.g., bending rigidity, and
      finite element analyses (FE) to predict the strength of isolated vertebral bodies
      under anterior bending boundary conditions. SUMMARY OF BACKGROUND DATA: Although
      the relative performance of QCT-based structural measures is well established for
      uniform compression, the ability of these techniques to predict vertebral
      strength under nonuniform loading conditions has not yet been established.
      METHODS: Thirty human thoracic vertebrae from 30 donors (T9-T10, 20 female, 10
      male; 87 +/- 5 years of age) were QCT scanned and destructively tested in
      anterior bending using an industrial robot arm. The QCT scans were processed to
      generate specimen-specific FE models as well as trabecular bone mineral density
      (tBMD), integral bone mineral density (iBMD), and MOS measures, such as axial and
      bending rigidities. RESULTS: Vertebral strength in anterior bending was poorly to
      moderately predicted by QCT-based BMD and MOS measures (R2 = 0.14-0.22). QCT
      based FE models were better strength predictors (R2 = 0.34-0.40); however, their
      predictive performance was not statistically different from MOS bending rigidity
      (P > 0.05). CONCLUSIONS: Our results suggest that the poor clinical performance
      of noninvasive structural measures may be due to their inability to predict
      vertebral strength under bending loads. While their performance was not
      statistically better than MOS bending rigidities, QCT-based FE models were
      moderate predictors of both compressive and bending loads at failure, suggesting
      that this technique has the potential for strength prediction under nonuniform
      loads. The current FE modeling strategy is insufficient, however, and significant
      modifications must be made to better mimic whole bone elastic and inelastic
      material behavior.

PMID- 17450079
TI  - Self-report outcome measures for low back pain: searching for international cross
      cultural adaptations.
AB  - STUDY DESIGN: Systematic review. OBJECTIVES: To describe the available cross
      cultural adaptations of low back pain (LBP) self-report outcome measures and the
      psychometric testing that has occurred for each adaptation. SUMMARY OF BACKGROUND
      DATA: Self-report measures are commonly used in clinical practice and in research
      studies. Most existing questionnaires were developed in English, and it is not
      clear how many have been adapted to other languages. METHODS: Two different
      searches on MEDLINE, EMBASE, CINAHL, and LILACS were performed. The first search
      identified questionnaires specifically designed for patients with LBP. The second
      search combined the name of the questionnaire with 35 different languages in
      order to locate cross-cultural adaptations of the questionnaire. Data on the
      psychometric testing of the translated questionnaires were extracted. RESULTS:
      Forty questionnaires were identified, only 15 of which had been adapted to a new
      language. Only 19 of the 35 different languages we searched for were represented
      in the search results. From 1400 possible adaptations, only 61 have been
      completed. Psychometric testing of the adapted questionnaires was quite variable
      and in general suboptimal with testing usually restricted to an assessment of
      reliability and construct validity. CONCLUSIONS: There is a clear need for
      further cross-cultural adaptation of LBP self-report measures and for greater
      attention to the quality of psychometric evaluation of adapted questionnaires.
      Without appropriately adapted measures, the clinical management of LBP patients
      who do not speak English is potentially compromised.

PMID- 17450080
TI  - Neck and shoulder pains in relation to physical activity and sedentary activities
      in adolescence.
AB  - STUDY DESIGN: A cross-sectional survey among adolescents aged 15-16 years.
      OBJECTIVE: To evaluate whether physical activity or sedentary activities
      associate with neck and shoulder symptoms among adolescents. SUMMARY OF
      BACKGROUND DATA: Findings of associations between physical exercise and neck or
      shoulder pain in adolescents are controversial. METHODS: The study population
      consisted of adolescents belonging to the Northern Finland Birth Cohort 1986. The
      present analyses included 3185 girls and 2808 boys. Associations of physical
      activity level, total sitting time, and different kinds of sedentary activities
      with neck or occipital pain and shoulder pain were analyzed at 15-16 years of age
      using logistic regression. Reporting pain (not seeking medical help) and
      consultation for pain (seeking medical help) were assessed separately in girls
      but were combined in boys because of a low prevalence of severe pain. RESULTS:
      Almost half of the girls and one third of the boys reported mild neck or
      occipital pain, or shoulder pain, and 5% of girls and 2% of boys reported severe
      neck or occipital pain, or shoulder pain during the past 6 months. High-level
      physical activity associated with an increased prevalence of both severe neck or
      occipital pain and severe shoulder pain in girls, but not in boys. Prolonged
      sitting was associated with a high prevalence of neck or occipital pain and
      shoulder pain in girls, and neck or occipital pain in boys. Of various sedentary
      activities, television watching and reading books associated with neck or
      occipital pain in girls, whereas playing or working with a computer associated
      with neck or occipital pain in boys. In girls, television watching also
      associated with mild shoulder pain. CONCLUSIONS: Neck or occipital pain and
      shoulder pain are very common symptoms among adolescents, and both prolonged
      sitting and a high level of physical activity seem to be related to them.

PMID- 17450081
TI  - Do psychiatric disorders first appear preinjury or postinjury in chronic
      disabling occupational spinal disorders?
AB  - STUDY DESIGN: An epidemiologic prevalence study. OBJECTIVES: To clarify the
      temporal association between work-related injury claims and psychiatric disorders
      in patients with chronic disabling occupational spinal disorders (CDOSDs).
      SUMMARY OF BACKGROUND DATA: Few empirical data are available regarding the
      "chicken-or-egg" question of which occurs first: the injury or incident
      culminating in the painful CDOSD or the psychiatric disturbance. METHODS:
      Subjects attended a tertiary interdisciplinary rehabilitation program.
      Psychiatric disorders were assessed using the Structured Clinical Interview for
      the Diagnostic and Statistical Manual of Mental Disorders (SCID-DSM-IV).
      Psychiatric disorders were characterized as preexisting if they manifested
      themselves before the work-related injury claim (whether or not they resolved,
      continued, or reoccurred after injury). They were determined postinjury diagnoses
      only if they manifested for the first time after the injury claim. RESULTS: A
      total of 38.7% of the present cohort had at least one preexisting major
      psychiatric disorder, while 98.9% developed one or more psychiatric disorders for
      the first time after injury onset (57.9% when pain disorder was excluded). The
      percentage of patients with preexisting psychiatric disorders was lower than
      general population base rates (48%). The first onset of certain psychiatric
      disorders was found to be elevated in patients only after the work-related
      injury; these included Pain Disorder (95.7%), Major Depressive Disorder (49.7%),
      and Opioid Dependence (15%). Moreover, 5 times as many patients with MDD, and 10
      times as many with opioid dependence, developed these disorders for the first
      time after the injury. CONCLUSIONS: In general, psychiatric disturbance is not a
      risk factor for developing a CDOSD. Psychiatric disorders are much more likely to
      develop after the onset of the work injury, indicating that such injuries and
      accompanying stressors are likely to be precipitants, rather than consequences,
      of psychopathology.

PMID- 17450082
TI  - Consensus statement on mandatory registration of clinical trials.

PMID- 17450083
TI  - Reflux laryngitis: a feasible indication for laparoscopic antireflux surgery?
AB  - Laparoscopic fundoplication is a routine surgical approach in the treatment of
      moderate or severe gastro-esophageal reflux disease. However, there are still
      contradictions regarding supraesophageal symptoms as an indication for surgery.
      The aim of this study was to determine the subjective symptomatic outcome and
      objective laryngeal findings after antireflux surgery in patients with pH
      monitoring proven reflux laryngitis. Between 1998 and 2002, 40 patients with
      reflux laryngitis underwent laparoscopic Nissen fundoplication. Patients were
      referred to surgery and followed-up by a specialist in otorhinolaryngology.
      Subjective symptoms were collected by a structured questionnaire at a median
      follow-up of 42 months. The objective laryngeal findings improved from the
      preoperative situation; at 12 months after surgery, the otorhinolaryngeal status
      was improved in 92.3% (n=24) of the patients. However, only 38.5% (n=10) of these
      patients evaluated an improvement in their voice quality. Of all, 62.5% (n=25) of
      the patients reported no or only mild cough or voice hoarseness symptoms
      postoperatively, 22.5% (n=9) had moderate symptoms, and 15.0% (n=6) suffered from
      difficult supraesophageal symptoms. Ninety-five percent of the patients regarded
      the result of their surgery excellent, good, or satisfactory. Of all, 82.5%
      (n=33) of the patients would still choose surgery, 7.5% (n=3) would abstain from
      surgery, and 10% (n=4) of the patients were hesitant about their choice. For
      patients suffering from supraesophageal symptoms of gastro-esophageal reflux
      disease with objective evidence of pharyngeal acid exposure, laparoscopic Nissen
      fundoplication provides a good and alternative adding to current treatment.

PMID- 17450084
TI  - Results of laparoscopic surgery for colorectal cancer in palliative intent: short
      term end points in 331 patients in comparison with procedures in benign
      indications.
AB  - BACKGROUND AND AIMS: Colorectal surgery performed in palliative intent is a
      relatively common intervention. The present study investigates the question
      whether such interventions are suitable for laparoscopic procedure. PATIENTS AND
      METHODS: The data presented herein were collected from 4834 patients within the
      framework of a multicenter study initiated by the "Laparoscopic Colorectal
      Surgery Study Group (LCSSG)." In a subgroup analysis of 331 operated palliative
      intent patients, the short-term outcomes were evaluated and compared with those
      obtained in patients undergoing surgery for benign indications. RESULTS: Overall,
      the morbidity and mortality rates were significantly higher in the cancer
      patients than in patients with a benign indication, with no significant
      differences between the 2 groups in terms of intraoperative complications,
      conversion, and reoperation rates. The analysis of the individual complications
      revealed that the significant differences were due exclusively to the more
      frequent presence of general medical complications, and thus were unrelated to
      the laparoscopic procedure. CONCLUSIONS: The laparoscopic approach to the
      palliation of incurable colorectal carcinomas was associated with comparable
      results with regard to intraoperative complications, conversion, reoperation
      rates, and postoperative surgical complications in comparison with surgical
      procedures for benign indications, with significantly higher morbidity and
      mortality rates related solely to general-medical complications.

PMID- 17450085
TI  - The use of bioabsorbable seamguard during laparoscopic appendectomy.
AB  - The laparoscopic approach to appendectomy for acute appendicitis is becoming
      increasingly favored among surgeons. Endoscopic stapling remains a common
      approach for division of the appendix and mesoappendix, but staple line bleeding
      along the mesentery is commonly observed, occasionally demanding surgical control
      for complete hemostasis. Bioabsorbable seamguard was used as an adjunct to
      endoscopic stapling of the mesoappendix in 33 consecutive adult patients during
      laparoscopic appendectomy for acute appendicitis, with complete immediate staple
      line hemostasis observed by the operative surgeon in all cases. There were no
      intraoperative complications and no late infectious intra-abdominal
      complications. There were no postoperative bleeding complications. Bioabsorbable
      seamguard is a safe and effective adjunct to endoscopic mesoappendiceal stapling
      which prevents intraoperative and postoperative staple line bleeding.

PMID- 17450086
TI  - Retromuscular sutured incisional hernia repair: a randomized controlled trial to
      compare open and laparoscopic approach.
AB  - To compare the early and intermediate results of the open and laparoscopic
      tension-free repair of incisional hernia, 24 patients were randomized
      prospectively to undergo laparoscopic or open repair of incisional hernia with
      retromuscular placement of the prosthesis using transabdominal sutures for mesh
      fixation. All the procedures were completed as planned. The mean duration of
      surgery was not significantly different between the 2 groups (P=0.15). Time to
      oral solid food intake was longer in the open group (P=0.002). The analgesic
      requirement was lower in the laparoscopic group (P=0.05). One patient after open
      surgery and 2 in the laparoscopic group suffered postoperative complications
      (P=0.71). Postoperative stay was shorter in the laparoscopic group (P=0.006). No
      readmission or recurrence was registered within 6 months from surgery in either
      group. Laparoscopic incisional hernia repair, based on the Rives-Stoppa
      technique, is a safe, feasible alternative to open techniques. However, larger
      studies and long-term follow-up are required to further evaluate the true
      effectiveness of this operation.

PMID- 17450087
TI  - Lightweight partially absorbable monofilament mesh (polypropylene/poliglecaprone
      25) for TAPP inguinal hernia repair: initial experience.
AB  - OBJECTIVE: An ideal mesh should produce slight foreign-body reactions and be
      compatible with the human organisms. Studies focusing on these aspects indicate
      that the use of mesh with less nonabsorbable material may reduce postoperative
      complications, insofar the web structure and its rigidity play an important role
      in compatibility. We evaluated retrospectively the patients of the past 1 year,
      who underwent laparoscopic transabdominal preperitoneal (TAPP) hernioplasty
      (without the use any trocar and/or instrument of 10 mm in diameter) focusing
      attention on the feasibility of the technique and on the incidence of
      complications, especially those possibly related to the new type of mesh
      implanted. METHODS: Between June 2004 and September 2005, 76 patients have been
      operated on by using TAPP hernioplasty (bilateral or unilateral) without any 10
      mm instrument/optic/trocar, and by applying a lightweight composite mesh fixed by
      "glues" (fibrin sealant and N-butyl 2-cyanoacrylate). RESULTS: The mean overall
      operative time was 55.57 (+/-15.2) minutes. All the procedures have been
      performed on a day surgery basis. We have registered any kind of major or minor
      morbidity (early or late), relapse, prosthesis rejection, and/or infection. We
      have registered no severe pain at 10 days; whereas a mild pain is still reported
      in 10.5% of our cases at a 3-month follow-up. The mean follow-up is 12.4 (+/-5.1;
      range 4 to 19) months. CONCLUSIONS: On the basis of this our initial experience,
      TAPP hernioplasty with a lightweight composite mesh is feasible, effective, and
      easy to perform by experienced hands, with good results. The well-known
      characteristics of a mini-invasive and gentle approach, together with the type of
      mesh implanted and its fixation of related glues, might explain the encouraging
      results of our experience.

PMID- 17450088
TI  - Laparoscopic herniorrhaphy combined ligation of the hernial sac and suturation of
      the internal ring in children with indirect inguinal hernias.
AB  - OBJECTIVE: To develop and evaluate the laparoscopic herniorrhaphy combined
      ligation of the hernial sac and suturation of the internal ring in children with
      indirect inguinal hernias. METHODS: Fifty-one indirect hernias in consecutive 41
      children with indirect hernias underwent the herniorrhaphy from January 2003 to
      August 2005. The general information, operating time, postoperative duration in
      hospital, duration return to normal activity, operative faults, and complications
      were collected. RESULTS: No recurrence was found in the whole group of the
      patients during 1 month to 32 months follow-ups, 1 case complicated with
      postoperative hydrocele and 3 cases with inguinal pain. CONCLUSIONS: The
      laparoscopic procedure combined ligation of the hernial sac and suturation of the
      internal ring is a brand new, feasible, reliable, and efficient herniorrhaphy for
      pediatric inguinal indirect hernias.

PMID- 17450089
TI  - Laparoscopic coagulation of uterine myomas with the use of a unipolar electrode.
AB  - The aim of this study was to evaluate the effectiveness of a laparoscopic
      myolysis with the use of a unipolar electrode. Forty-six patients, 25 to 52 years
      old with symptomatic myomas (menometrorrhagia or/and pelvic pain) were included
      in the study. A transvaginal ultrasound showed 1 or 2 intramural or/and
      subserosal leiomyomata of 1 to 4.5 cm in diameter. Patients were selected to
      undergo a laparoscopic coagulation of myomas. Subsequently, they were followed-up
      6 months after the treatment. Symptoms reduction and myoma size reduction were
      evaluated. In addition, all the patients underwent transvaginal Doppler
      ultrasounds to assess the blood flow in the uterine arteries. In the study group,
      the disappearance of myomas was observed in 52.2% of patients 6 months after the
      therapy. In other patients, the mean myoma shrinkage amounted to 76%. The myoma
      volume reduction was correlated with an increase in the resistance index (P=0.02)
      and the pulsatility index (P=0.11) of the right and left uterine arteries.

PMID- 17450090
TI  - Retrospective comparison of needle thoracoscopy and conventional thoracoscopic
      surgery to treat primary spontaneous pneumothorax.
AB  - OBJECTIVE: To retrospectively compare needle video-thoracoscopic surgery (NVTS)
      with conventional video-thoracoscopic surgery (CVTS) for the treatment of primary
      spontaneous pneumothorax. METHODS: The charts of 9 female and 66 male patients
      with onset of primary spontaneous pneumothorax between July 1999 and December
      2005 were reviewed. Twenty-two patients in the NVTS group were treated with NVTS,
      using a needle-shaped thoracoscope and instruments (3-mm in diameter), and
      assisted by one 10-mm standard port, whereas 53 patients in the CVTS group were
      treated using conventional endoscopic devices with a 10-mm thoracoscope. All
      patients underwent endoscopic stapling to excise blebs if identified.
      Postoperative wound pain was scored using a numerical pain scale. RESULTS:
      Neither group experienced mortality or any major morbidity during mean follow-up
      of 80.5 months. In the NVTS and CVTS groups, intraoperative blood loss (11.4+/
      14.8 and 17.4+/-18.1 mL respectively, P=0.174), and mean operative times (75.5+/
      38.5 and 92.2+/-33.1 min, respectively, P=0.062) did not differ significantly.
      Mean durations of pleural drainage (0.6+/-1.0 and 2.6+/-2.3 d, respectively,
      P<0.01), and postoperative hospital stay (2.3+/-1.4 and 4.4+/-2.5 d,
      respectively, P<0.01) were less in the needle video-thorascopic surgery group.
      The degree of postoperative wound pain did not differ significantly between the 2
      groups. There were 3 cases of persistent postoperative air leakage in both
      groups, which required further approaches to check for unrecognized blebs. There
      was no recurrence of pneumothorax in the NVTS group, and 3.6% recurrence rate in
      the CVTS group. CONCLUSIONS: Needle thoracoscopy seems to be a safe alternative
      to treat primary spontaneous pneumothorax.

PMID- 17450091
TI  - Hand-assisted laparoscopic esophagojejunostomy using newly developed purse-string
      suture instrument "Endo-PSI".
AB  - Although there are several reports on the esophagojejunostomy during laparoscopy
      assisted total gastrectomy, the procedures still remain to be established. We
      report hand-assisted laparoscopic esophagojejunostomy using circular stapler and
      newly developed instrument "Endo-PSI." Between April 2005 and April 2006, 13
      patients received these products during laparoscopy-assisted total gastrectomy.
      The Endo-PSI was attached to the abdominal esophagus using hand-assisted
      laparoscopic surgery. The insertion of the straight needle with 2-0 polypropylene
      into the device and the cutting of the esophagus were also performed using hand
      assisted laparoscopic surgery. The insertion of the anvil head into the esophagus
      and the ligation of the purse-string suture were performed laparoscopically.
      After the jejuno-jejunal anastomosis was performed extracorporeally, the
      combination of the circular stapler for esophagojejunostomy and the closure of
      the stump of the jejunum were performed laparoscopically. There were no
      complications attributable to this procedure and there were no cases that
      required conversion to conventional open procedure or required extension of
      median incision. This newly developed Endo-PSI was useful for laparoscopic purse
      string suture.

PMID- 17450092
TI  - Laparoscopic intragastric full-thickness excision (LIFE) of early gastric cancer
      under flexible endoscopic control--introduction of new technique using animal.
AB  - BACKGROUND: We have developed a new method for the treatment of stomach lesions
      in early gastric cancer, which we refer to as laparoscopic intragastric full
      thickness excision under flexible endoscopic control. In this procedure, the
      diseased lesion of the gastric wall is pulled inwards and removed under endoscopy
      and laparoscopy guidance. A lesion in the anterior wall of the stomach, for which
      a direct percutaneous transgastric puncture can be performed, is a good
      indication for laparoscopic intragastric full-thickness excision, similarly to
      the lesion-lifting method. The purpose of the study is to describe the surgical
      techniques in the procedure and to assess the clinical relevance of the approach.
      SURGICAL TECHNIQUE: Three trocars are used in the normal procedure. To perform
      sentinel lymph node navigation surgery, indocyanine green is injected into the
      submucosal layer in 4 quadrants under endoscopy. The periphery of the lesion is
      punctured with the first trocar (trocar(1)) by the percutaneous transgastric
      route. The wire of the T-bar is introduced into the stomach through trocar(1).
      The tip of the wire is pulled into the stomach using the forceps of the
      endoscope. The T-bar, after passing through the abdominal wall, is fixed outside
      the gastric wall. The second trocar (trocar(2)) is placed at the subumbilical
      region in the abdominal cavity to accommodate the laparoscope, whereas the third
      trocars (trocar(3)) are percutaneously punctured into the abdominal cavity. The
      indocyanine green-colored sentinel lymph node is detected using instruments
      positioned through trocar(1) and trocar(3), and the absence of lymph node
      metastasis is quickly confirmed by pathologic examination. Trocar(3) is
      repositioned in the stomach by the percutaneous transgastric route. The stomach
      anterior wall is pulled inwards by the T-bar, and the lesion is removed by
      several excisions with laparoscopic stapling devices inserted through trocar(3);
      extraction of the specimen is achieved through trocar(3). The gastrotomy site is
      sutured using instruments positioned through trocar(1) and trocar(3) under
      laparoscopy. The stomach surgery is performed under gastroscopic guidance,
      whereas the intra-abdominal procedures are performed under laparoscopy.
      CONCLUSIONS: On the basis of the introduction of new technique using pigs, we
      believe that this procedure is useful for intramucosal carcinoma, which exceeds
      the standard indication for endoscopic mucosal resection, and for carcinoma
      invading the submucosa without lymph node metastasis.

PMID- 17450093
TI  - Laparoscopic pericardio-peritoneal window: an alternative approach in the
      treatment of recurrent pericardial effusion, in-hospital evolution and survival.
AB  - BACKGROUND: Although cardiac tamponade due to pericardial effusion is not
      frequently seen it may, in many cases require surgical drainage. The aim of this
      study is to show our experience with a laparoscopic approach to perform the
      pericardio-peritoneal window in the management of recurrent pericardial effusion.
      METHODS: We included 16 patients with recurrent pericardial effusion and
      echocardiographic global tamponade. A pneumoperitoneum was made and 3 trocars
      were placed; an avascular area of the diaphragm was chosen and a pericardial
      window was made (4 cm diameter). RESULTS: Pericardial-peritoneal window was
      carried out successfully (mean operative time 40 min). All patients presented
      relief of symptoms. The mean follow-up was 729 days. No patient experienced
      recurrence on repeated ecocardiographic examinations. There were no fatal events
      related to the procedure. CONCLUSIONS: Laparoscopic pericardial window is a
      simple, safe, and effective alternative for the treatment of recurrent
      pericardial effusion with global cardiac tamponade.

PMID- 17450094
TI  - Epidural catheters can facilitate laparoscopic placement of ureteral stent:
      description of a technique.
AB  - AIM: To introduce a novel technique for laparoscopic placement of ureteral stent
      and to investigate the safety and effectiveness of this new method. METHODS:
      Fourteen patients underwent laparoscopic placement of ureteral stents with the
      technique. The stent was indwelled with an epidural catheter, delivered to the
      operative field, and placed through the ureteral incision into the renal pelvis
      and bladder, respectively. The stent was then secured with pincers, while the
      epidural catheter was removed. RESULTS: With this method, the ureteral stent
      insertion is very convenient and time saving (the mean time for inserting a stent
      was 2.7 min). The stents were successfully inserted into 13 patients once. One
      patient underwent insertion of the stent twice intraoperatively. Thirty days
      after the operations, none of double-J stents had migrated out of the renal
      pelvis or bladder. CONCLUSIONS: This technique is reliable and effective in
      laparoscopic ureteral operations. Its use should be generalized in laparoscopic
      ureteral operations.

PMID- 17450095
TI  - Minimally invasive percutaneous nephrolithotomy for staghorn calculi: a novel
      single session approach via multiple 14-18Fr tracts.
AB  - OBJECTIVE: To report our experience with minimally invasive percutaneous
      nephrolithotomy (MPCNL) (14-18Fr percutaneous tract) to treat staghorn calculi
      via multiple percutaneous tracts in a single session procedure, and evaluate the
      feasibility and efficiency of this technique. PATIENTS AND METHODS: From March
      2001 to November 2005, 100 patients with staghorn calculi were treated by MPCNL
      via multiple percutaneous tracts. The size and location of the stone, operative
      parameters, number of tracts, stone-free rate, operating time, hospital stay, and
      complications were analyzed retrospectively. RESULTS: A total of 209 percutaneous
      tracts were established in 100 renal units during 128 operations including 28
      second-look procedures. The mean operating time was 107 minutes (range 43 to 130
      min) and the mean hospital stay was 9.4 days (range 6 to 13 d). The initial stone
      clearance rate of 72% after the first session was improved to 93% after a second
      look procedure in 28 patients. The mean blood loss was 112 mL (range 64 to 483
      mL), 3 patients required blood transfusion and 1 patient with branched renal
      arterial injury during puncture received a highly elective embolism. Seven
      patients had a postoperative fever of 38.5 degrees C or greater, whereas 4
      patients had mild hydropneumothorax. CONCLUSIONS: With the development of
      instrument and increased experience, judiciously made multiple percutaneous
      tracts in a single session MPCNL for treating staghorn calculi in selected cases
      is safe, feasible, and efficient with an acceptable morbidity.

PMID- 17450096
TI  - Laparoscopic removal of a gastric trichobezoar in a pregnant woman.
AB  - We describe the laparoscopic removal of a gastric trichobezoar performed on an 18
      year-old woman in her second trimester of pregnancy. The laparoscopic removal of
      a gastric trichobezoar has not previously been described in an adult. Laparoscopy
      during pregnancy is never without the fear of harm including spontaneous abortion
      of the developing fetus, however, increasing cumulative worldwide experience
      suggests that there is no significant difference in fetal morbidity with
      laparoscopy when compared with laparotomy. A review of laparoscopy in pregnancy
      with regard to this case is presented.

PMID- 17450097
TI  - Laparoscopic approach of gastric gastrointestinal stromal tumors (GISTs): is it
      still a courageous choice? Report of two cases.
AB  - Gastrointestinal stromal tumors (GISTs) are a well-defined clinicopathologic and
      molecular tumor entity, representing the most common gastrointestinal mesenchymal
      neoplasm. Differential diagnosis between GIST and other mesenchymal malignancies
      is crucial, given the successful management using targeted therapy in metastatic
      GIST. The mainstay of treatment remains surgery, complete tumor resection being
      the most important independent prognostic factor. Videolaparoscopic approach is
      still controversial for the high risk of tumor rupture or bleeding. Here we
      report 2 cases of GIST surgically resected using a videolaparoscopic approach and
      discuss the efficacy of this technique in selected patients.

PMID- 17450098
TI  - An unusual bile collection after postcholecystectomy bile leakage.
AB  - Leakage from the cystic duct stumps accounts for the majority of postlaparoscopic
      cholecystectomy leaks. It commonly presents with a localized bile collection in
      the gallbladder fossa and endoscopic retrograde cholangiopancreatography (ERCP)
      with biliary stenting is a common method of treatment. However, bile may collect
      in other intra-abdominal locations away from the gallbladder fossa. We present
      here a case of a patient who developed upper abdominal pain with distension,
      anorexia, and vomiting a week after laparoscopic cholecystectomy. Ultrasonography
      and computed tomography scans showed an intra-abdominal collection and ERCP
      showed a cystic duct stump leak. A biliary stent was inserted and the collection
      was percutaneously drained. His symptoms, however, recurred 2 weeks later, with
      fever, anorexia, and weight loss. Abdominal computed tomography scan showed
      9.3x8.5 cm cystic mass in the left hypochondriac area and ERCP showed persistent
      leakage from the cystic duct stump. The stent was changed to a larger size Fr12
      and the collection was again drained percutaneously. His clinical condition
      improved dramatically. The biliary stent was removed after 8 weeks and remained
      well at 9-month follow-up.

PMID- 17450099
TI  - Isolated metastatic melanoma to the gallbladder: is laparoscopic cholecystectomy
      indicated?: a case report and review of the literature.
AB  - Metastatic involvement of the gallbladder in melanoma is rare, but constitutes
      the most common metastatic lesion involving this organ. The surgical management
      seems to be indicated for patients with isolated and resectable gallbladder
      metastases to avoid symptoms or tumor complications. We report on a case of a
      young woman with an isolated metastatic gallbladder melanoma who presented with
      symptoms of acute cholecystitis. The patient underwent laparoscopic
      cholecystectomy (LC) and lymphadenectomy of the hepatoduodenal ligament.
      Histology was characteristic for metastatic malignant melanoma. Nodes were
      negative for metastases. We emphasize the appropriateness of a laparoscopic
      approach, once ruled out a widespread metastatic disease. It can be done with a
      remarkably low rate of complications. Gentle manipulation, avoidance of
      perforation, and use of a retrieval bag for the removal of the gallbladder should
      be practiced to help minimize the chance of mechanical exfoliation or
      implantation of malignant cells during LC. In isolated metastatic localization,
      LC may be curative and provide adequate palliation of symptoms with a short
      convalescence and a fast recovery.

PMID- 17450100
TI  - Use of endoscopic snare to extract a large rectosigmoid foreign body with review
      of literature.
AB  - Rectal foreign bodies are common and various shapes and sizes have been described
      in literature. Large objects impacted high in the rectosigmoid junction pose a
      challenge for endoscopic extraction. We describe a method that successfully
      removed a 15x6x3.5-cm shampoo bottle impacted in the rectosigmoid junction. A 50
      year-old man had passed a shampoo bottle up into his rectum. Examination revealed
      a lax sphincter but the bottle could not be felt. Contrast x-rays showed a well
      delineated bottle in the rectosigmoid junction with no evidence of bowel
      perforation. A flexible sigmoidoscope with an endoscopic snare was used to
      "lasso" the foreign body and deliver it out. A check sigmoidoscopy after
      extraction showed no bleeding or perforation. This technique is a safer and less
      morbid method of extracting impacted high rectal foreign bodies, in the absence
      of perforation. It should be attempted before open surgical removal.

PMID- 17450102
TI  - Pregnancy rates and birth outcomes among women on efavirenz-containing highly
      active antiretroviral therapy in Botswana.
AB  - BACKGROUND: Millions of HIV-infected women in developing countries are in need of
      safe and highly effective antiretroviral therapy. Pregnancy rates are usually
      high in developing countries, and efavirenz (EFV) use in women of childbearing
      age is of concern because of its potential teratogenicity. METHODS: As part of a
      prospective study comparing 6 initial highly active antiretroviral therapy
      (HAART) regimens, 3 of which contained EFV, pregnancy and birth outcomes were
      evaluated among female participants enrolled in a randomized clinical trial in
      Botswana. Before enrollment, all female participants indicated a willingness to
      avoid pregnancy for the 3-year duration of the study. Monthly urine pregnancy
      testing and regular contraceptive education and counseling were given to all
      women on study. RESULTS: Four hundred fifty-one (69.4%) of 650 enrolled study
      participants were female and experienced 71 pregnancies, for a rate of 7.9 per
      100 person-years during the study. The mean time from HAART initiation to time of
      first pregnancy was 385 days. The median birth weight of babies was 2950 g
      (interquartile range: 2700-3250 g); the gender of babies (24 female and 15 male)
      and occurrence of early pregnancy loss (42%) and stillbirths (3%) did not differ
      between EFV- and non-EFV-exposed pregnancies (P=0.7). First-trimester EFV
      exposure occurred in 38 (53.5%) of the 71 pregnancies; 22 (57.9%) of these 38
      pregnancies resulted in live births. One infant (4.5%) of the 22 EFV-exposed live
      births had a congenital abnormality with right limb shortening that was assessed
      to be unrelated to EFV exposure. CONCLUSIONS: The restoration of health and
      longevity in many HAART-treated women is often accompanied by childbearing, as
      evidenced by the large fraction of women in our cohort who became pregnant
      despite their initial statements of intent to avoid pregnancy. Of 22 first
      trimester EFV-exposed live births, 1 neonate was found to have a major congenital
      abnormality; however, this defect was unrelated to EFV exposure. The small sample
      size is insufficient to estimate accurately the underlying risk of congenital
      malformation after exposure to EFV in early pregnancy, underscoring the
      importance of reporting to the existing international Antiretroviral Pregnancy
      Registry. In addition to accessing safe and effective HAART regimens, HIV
      infected women require access to comprehensive family planning services,
      including contraception and procreation counseling.

PMID- 17450104
TI  - Ototoxic effect of Burow solution applied to the guinea pig middle ear.
AB  - OBJECTIVE: To analyze the ototoxicity of Burow solution as an otologic
      preparation. BACKGROUND: Burow solution has been used for years in the treatment
      of acute or chronic otitis externa and chronic suppurative otitis media. This
      acidic solution has antibacterial and antiedematous properties. Ototoxic effect
      of Burow solution has not been known, so the current study was designed to
      observe the ototoxic effect of Burow solution experimentally. MATERIALS AND
      METHODS: Experiments were performed in 32 young, male albino guinea pigs (weight,
      450-550 g). Twenty animals in the experimental group were divided into 2 groups
      of 10 animals each. The first group received 13% Burow solution (13% aluminum
      subacetate), and the second received 4% Burow solution (4% aluminum subacetate).
      Twelve animals in the control group were divided into 2 groups of 6 animals each.
      The first group received gentamicin (40 mg/mL; ototoxic control), and the second
      received saline solution (negative control). Under general anesthesia,
      pretreatment auditory brainstem responses (ABRs) from the right ear were obtained
      from the animals in all groups. The right tympanic membranes were widely
      perforated, and a small piece of Gelfoam was applied to the middle ear. Ear
      solutions at concentrations of 0.1 mL were applied through transcanal approach to
      the middle ear twice a day in 10 days. Under general anesthesia, the Gelfoam was
      removed from the right middle ear, and posttreatment ABRs were obtained 14 days
      later after the initial time in all groups. RESULTS: Baseline ABR results were
      normal in right ears of all animals tested. Animals undergoing placement of
      Gelfoam with either 13% Burow solution, 4% Burow solution, or saline in the
      middle ear showed no changes in ABR threshold. The gentamicin group showed
      significant change in the ABR threshold. CONCLUSION: Burow solution was
      considered to be an effective and safe otologic preparation.

PMID- 17450108
TI  - Ginkgo biloba extract (EGb 761) protects against cisplatin-induced ototoxicity in
      rats.
AB  - HYPOTHESIS: A standardized Ginkgo biloba extract, EGb 761, may have protective
      effect against cisplatin-induced ototoxicity in rats. BACKGROUND: Cisplatin
      induced ototoxicity is a major dose-limiting side effect in anticancer
      chemotherapy. Cisplatin-induced ototoxicity has been correlated to depletion of
      the cochlear antioxidant system and increased lipid peroxidation. EGb 761
      contains potent antioxidants capable of scavenging free radicals, inhibiting
      nitric oxide synthesis, reducing lipid peroxidation, and protecting against
      apoptosis. The purpose of this study was to investigate the effect of EGb 761 on
      cisplatin-induced ototoxicity in rats. METHODS: Male Wistar rats were divided
      into four groups and were treated as follows: 1) vehicle control; 2) cisplatin
      (13 mg/kg, intraperitoneally) plus vehicle; 3) EGb 761 (200 mg/kg,
      intraperitoneally); and 4) EGb 761 plus cisplatin. Auditory brainstem responses
      (ABRs) were measured pretreatment and 72 hours posttreatment, and threshold
      shifts were analyzed. Endocochlear potentials (EPs) were also obtained at 72
      hours posttreatment. Cochleae were harvested and processed for scanning electron
      microscopy after completion of auditory testing. RESULTS: Cisplatin-treated rats
      showed significant ABR threshold shifts across all frequencies (click, and 2-, 4
      , 8-, 16-, and 32-kHz tones) compared with each of the other groups (p < 0.001).
      Rats treated with EGb 761 plus cisplatin did not show significant ABR threshold
      shifts (p > 0.05). Similarly, the EPs of cisplatin-treated rats were decreased
      significantly approximately 50% in comparison with the other groups (p < 0.001).
      The EPs of EGb 761 plus cisplatin-treated rats were decreased less than 20%
      compared with vehicle control group or the EGb 761 only group (p < 0.01). The
      scanning electron microscopy observation indicated severe outer hair cell loss in
      the basal turn of cochleae of cisplatin-treated rats, whereas outer hair cells
      remained intact in the rats treated with EGb 761 plus cisplatin. CONCLUSION:
      These results demonstrate that EGb 761 protects against cisplatin-induced
      ototoxicity.

PMID- 17450111
TI  - Obesity in childhood: introduction and general considerations.

PMID- 17450112
TI  - Drugs for female sexual dysfunction.

PMID- 17450113
TI  - Panitumumab (Vectibix) for metastatic colorectal cancer.

PMID- 17450114
TI  - Choice of antibacterial drugs.

PMID- 17450115
TI  - Development of microchip for rapid pretreatment of trichloroethylene and
      tetrachloroethylene volatilized from polluted soil.
AB  - In the field of environmental analysis, microchip technology has many attractive
      features and is expected to realize the miniaturization of analytical instruments
      allowing on-site and multipoint monitoring using this technology. We propose a
      new soil analytical system for detecting trichloroethylene (TCE) and
      tetrachloroethylene (PCE) using a microchip. The experimental conditions for the
      pretreatment microchip were optimized. Under the optimized conditions, the
      detection limits of TCE and PCE were 15 and 9 ppbv, and the determination limits
      of TCE and PCE were 62 and 72 ppbv, respectively.

PMID- 17450116
TI  - A simplified estimation of loss of life expectancy (LLE) using rectangular
      approximation method.
AB  - In order to evaluate the effects of short exposure period using a simple
      methodology, a plain rectangular approximation method to estimate loss of life
      expectancy (LLE) was devised and applied to evaluate cancer risk. The posed risk
      was expressed as the time of LLE, which is proportional to the period and
      concentration of exposure. This method assumes a rectangular survival curve and a
      flat cancer risk for all ages. In the survival curve, the survival rate of the
      population studied declined due to the risk such that the new survival curve
      became a trapezoid. The area difference between the initial rectangle and the
      trapezoid was converted to an LLE value. Lifetime exposure to the acceptable
      level concentration (ALC), which is equivalent to a 10(-5) lifetime cancer risk,
      gave the base LLE, which was calculated to be 210 min. Exposure to the ALC
      between the ages of 20 and 25 years resulted in an LLE of 18.9 min, which is 9.0%
      of the base risk. One minute of exposure to carcinogens at 1000 x ALC is
      equivalent to an LLE of 0.0075 min. Considering that the ALC of benzene is 2
      microg/m(3), 1 min of exposure to 267 mg/m(3) benzene is equal to 1 min of LLE,
      which is as toxic as "smoking tobacco."

PMID- 17450117
TI  - Desorption/ionization on carbon mass spectrometry: study of amorphous-carbon
      property.
AB  - In this study, an amorphous carbon was proposed as a new ionization substrate for
      laser desorption/ionization (LDI) and its efficiency for soft laser ionization
      without any matrix molecules was focused on the soft laser ionization effect of
      the amorphous carbon substrate was compared with that of a stainless substrate by
      LDI and matrix-assisted laser desorption/ionization (MALDI) using a 266-nm
      irradiation laser. The result of the amorphous carbon substrate was indicated to
      have a soft ionization effect similar to the result of MALDI. In addition, from
      the experimental result achieved by soft laser ionization using not only 266-nm
      wavelength but also 355-nm-wave length irradiation lasers, the amorphous carbon
      substrate had a high degree of generality for selecting a sample similarly to
      soft ionization. The same experimental condition was carried out for other
      amorphous carbon substrates with different surface roughnesses in order to
      clarify the ionization mechanism on the amorphous carbon substrates. From the
      results, it was suggested that factors besides the difference in surface
      roughness exist for laser ionization efficiency.

PMID- 17450118
TI  - Complementary DNA cloning and organ expression of cytochrome P450 1C2 in carp
      (Cyprinus carpio).
AB  - Cytochrome P450 (CYP) genes, which make up a large gene superfamily, are known to
      play an important role in drug metabolism. The CYP1 family, one of the gene
      families of the CYP superfamily, has three subfamilies of genes whose sequences
      have been deposited in the GenBank/EMBL thus far: CYP1A, CYP1B, and CYP1C.
      Mammals as well as fish confront numerous foreign chemicals in the environment
      that may accumulate to toxic levels unless they are metabolized and eliminated by
      processes largely mediated by CYP enzymes. A new complementary DNA of the CYP1C
      subfamily encoding CYP1C2 was isolated from the carp liver after a single
      intraperitoneal injection of beta-napthoflavone (BNF). The full-length cDNA
      obtained contained a 5' noncoding region of 198 bp, an open reading frame of 1575
      bp coding for 524 amino acids and a stop codon, and a 3' noncoding region of 531
      bp. The predicted molecular weight of the protein was approximately 59.3 kDa. The
      amino acid sequence deduced from the carp CYP1C2 sequence showed a similarity of
      76.6% with that deduced from our previously reported carp CYP1C1. It exhibited
      similarities of 77.3, 73.7, and 76.4% with those deduced from scup CYP1C2, scup
      CYP1C1, and Japanese eel CYP1C1 sequences, respectively. Carp CYP1C2 cDNA showed
      similarities with reported CYP1Bs of teleosts and mammals, namely, 47.6, 45.3,
      45.7, 44.0, and 44.6% for carp, plaice, human, rat, and mouse CYP1B1s,
      respectively, while it exhibited a similarity of 49.0% with carp CYP1B2. The carp
      CYP1C2 sequence was aligned with the CYP1 sequences and has been deposited in the
      GenBank/EMBL data bank with the accession number AY437777. The phylogenetic tree
      constructed using fish and mammalian CYP1 sequences suggested a closer
      relationship of CYP1C with CYP1B than with CYP1A. The tree showed possibile
      existence of CYP1C subfamily genes in mammalian species. Northern blot analysis
      of the liver, intestines, kidneys, and gills revealed a distinct induced
      expression only in the kidneys, with no detectable constitutive expression in the
      other organs studied.

PMID- 17450119
TI  - Human intestinal cells incubated with activated sludge and lipopolysaccharide
      express Hsp90b.
AB  - Intestinal cells are the first line of defense against toxic substances that may
      enter the body orally. Some of these substances may emanate from wastewater
      treatment plants and thus may eventually enter the food chain. In this study,
      human intestinal Caco-2 cells were incubated with biologically treated activated
      sludge and lipopolysaccharide (LPS) to determine changes in protein expression
      and cell monolayer integrity. Caco-2 cells incubated for 3 h with 24-h-aerated
      activated sludge or 220 microg/ml LPS showed enhanced expression of the heat
      shock protein 90b (Hsp90b). The results further show that 220 microg/ml LPS is
      sufficient to irreversibly disrupt tight-junction permeability in 30 min. The
      Hsp90b expression by the Caco-2 cells incubated with biologically treated
      activated sludge may be a cellular protective mechanism against LPS-induced
      stress.

PMID- 17450120
TI  - Comparison of serum vitellogenin, steroid hormone, gonad histopathology and
      bioaccumulation in common carp (Cyprinus carpio) of two rivers and a lake in
      Japan: potential for endocrine disruption.
AB  - To investigate endocrine disruption and chemical contaminant levels in the
      aquatic environment, serum vitellogenin (Vtg) induction, steroid hormone
      synthesis, gonad histopathology and nonylphenol (NP) bioaccumulation were
      measured in common carp (Cyprinus carpio) in three sites (two rivers and one
      lake, in which high, medium, and low NP concentrations were detected in a
      previous study) in Japan from November 2001 to February 2002. The average
      gonadosomatic indexes (GSIs) for males were 3.9% in the Ishizu River, 5.6% in the
      Imba discharge channel, and 4.2% in Teganuma. No testis-ova in the gonads were
      found in any of the captured carp in this study. Abnormalities in testis were
      observed in individuals (n = 2/15) captured in the Imba discharge channel, and
      retraction and unusual cell proliferation were observed in the testis of the same
      fish. Serum Vtg was detected in 40% of the male samples captured in the Ishizu
      River and in 53% of the male samples captured in the Imba discharge channel. The
      levels of alkylphenols and bisphenol A, as well as estrogenic activity, were
      determined in the aquatic environment. In additional caging experiments in the
      Nikko River (medium NP concentration), male carp showed NP bioconcentration after
      the exposure to the river water.

PMID- 17450121
TI  - Characteristics of patients attending rapid access clinics during the West of
      Scotland Cancer Awareness Programme oral cancer campaign.
AB  - AIM: In 2003, the West of Scotland Cancer Awareness Programme (WoSCAP) launched
      their oral cancer campaign to raise public awareness of the disease in five NHS
      boards across the West of Scotland. The aim of this study was to evaluate the
      campaign by reviewing patients attending rapid access clinics in the 11 secondary
      care units across the five boards. DESIGN: Data were collected in 2004 during the
      second phase of the campaign via a two part self-completing questionnaire; the
      first part collected information from the patients and the second part from the
      clinicians, in rapid access clinics in the secondary care units. RESULTS: In
      total, 580 questionnaires were given out in the clinics with 538 completed
      patient sections (response rate 93%) and 500 completed clinician sections
      (response rate of 86%). More than two thirds of rapid access secondary care
      patients had seen a recent health campaign related to mouth cancer, and 46%
      responded that the campaign had encouraged them to seek advice more quickly. Of
      the patients examined in the clinics, 5% had a provisional diagnosis of a
      malignant lesion, 7% a potentially malignant lesion, and the majority of lesions
      were benign. The clinicians deemed 30% of the referrals to be inappropriate.
      CONCLUSIONS: The results show a high percentage of patients attending rapid
      access clinics were aware of the campaign. However, there were a disproportionate
      number of inappropriate referrals to the rapid access clinics compared to
      genuinely urgent cases.

PMID- 17450122
TI  - OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells.
AB  - Although oxidative damage has long been associated with ageing and neurological
      disease, mechanistic connections of oxidation to these phenotypes have remained
      elusive. Here we show that the age-dependent somatic mutation associated with
      Huntington's disease occurs in the process of removing oxidized base lesions, and
      is remarkably dependent on a single base excision repair enzyme, 7,8-dihydro-8
      oxoguanine-DNA glycosylase (OGG1). Both in vivo and in vitro results support a
      'toxic oxidation' model in which OGG1 initiates an escalating oxidation-excision
      cycle that leads to progressive age-dependent expansion. Age-dependent CAG
      expansion provides a direct molecular link between oxidative damage and toxicity
      in post-mitotic neurons through a DNA damage response, and error-prone repair of
      single-strand breaks.

PMID- 17450123
TI  - A positive feedback mechanism governs the polarity and motion of motile cilia.
AB  - Ciliated epithelia produce fluid flow in many organ systems, ranging from the
      respiratory tract where it clears mucus to the ventricles of the brain where it
      transports cerebrospinal fluid. Human diseases that disable ciliary flow, such as
      primary ciliary dyskinesia, can compromise organ function or the ability to
      resist pathogens, resulting in recurring respiratory infections, otitis,
      hydrocephaly and infertility. To create a ciliary flow, the cilia within each
      cell need to be polarized coordinately along the planar axis of the epithelium,
      but how polarity is established in any ciliated epithelia is not known. Here we
      analyse the developmental mechanisms that polarize cilia, using the ciliated
      cells in the developing Xenopus larval skin as a model system. We show that cilia
      acquire polarity through a sequence of events, beginning with a polar bias set by
      tissue patterning, followed by a refinement phase. Our results indicate that
      during refinement, fluid flow is both necessary and sufficient in determining
      cilia polarity. These findings reveal a novel mechanism in which tissue
      patterning coupled with fluid flow act in a positive feedback loop to direct the
      planar polarity of cilia.

PMID- 17450124
TI  - A chromatin link that couples cell division to root epidermis patterning in
      Arabidopsis.
AB  - Cell proliferation and cell fate decisions are strictly coupled processes during
      plant embryogenesis and organogenesis. In the Arabidopsis thaliana root
      epidermis, expression of the homeobox GLABRA2 (GL2) gene determines hair/non-hair
      cell fate. This requires signalling of positional information from the underlying
      cortical layer, complex transcriptional regulation and a change in chromatin
      accessibility. However, the molecular connections among these factors and with
      cell division are not known. Here we have identified a GL2-expression modulator,
      GEM, as an interactor of CDT1, a DNA replication protein. GEM also interacts with
      TTG1 (TRANSPARENT TESTA GLABRA1), a WD40-repeat protein involved in GL2-dependent
      cell fate decision, and modulates both cell division and GL2 expression. Here we
      show that GEM participates in the maintenance of the repressor histone H3K9
      methylation status of root patterning genes, providing a link between cell
      division, fate and differentiation during Arabidopsis root development.

PMID- 17450125
TI  - PTC124 targets genetic disorders caused by nonsense mutations.
AB  - Nonsense mutations promote premature translational termination and cause anywhere
      from 5-70% of the individual cases of most inherited diseases. Studies on
      nonsense-mediated cystic fibrosis have indicated that boosting specific protein
      synthesis from <1% to as little as 5% of normal levels may greatly reduce the
      severity or eliminate the principal manifestations of disease. To address the
      need for a drug capable of suppressing premature termination, we identified
      PTC124-a new chemical entity that selectively induces ribosomal readthrough of
      premature but not normal termination codons. PTC124 activity, optimized using
      nonsense-containing reporters, promoted dystrophin production in primary muscle
      cells from humans and mdx mice expressing dystrophin nonsense alleles, and
      rescued striated muscle function in mdx mice within 2-8 weeks of drug exposure.
      PTC124 was well tolerated in animals at plasma exposures substantially in excess
      of those required for nonsense suppression. The selectivity of PTC124 for
      premature termination codons, its well characterized activity profile, oral
      bioavailability and pharmacological properties indicate that this drug may have
      broad clinical potential for the treatment of a large group of genetic disorders
      with limited or no therapeutic options.

PMID- 17450126
TI  - Chitin induces accumulation in tissue of innate immune cells associated with
      allergy.
AB  - Allergic and parasitic worm immunity is characterized by infiltration of tissues
      with interleukin (IL)-4- and IL-13-expressing cells, including T-helper-2 cells,
      eosinophils and basophils. Tissue macrophages assume a distinct phenotype,
      designated alternatively activated macrophages. Relatively little is known about
      the factors that trigger these host responses. Chitin, a widespread environmental
      biopolymer of N-acetyl-beta-D-glucosamine, provides structural rigidity to fungi,
      crustaceans, helminths and insects. Here, we show that chitin induces the
      accumulation in tissue of IL-4-expressing innate immune cells, including
      eosinophils and basophils, when given to mice. Tissue infiltration was unaffected
      by the absence of Toll-like-receptor-mediated lipopolysaccharide recognition but
      did not occur if the injected chitin was pre-treated with the IL-4- and IL-13
      inducible mammalian chitinase, AMCase, or if the chitin was injected into mice
      that overexpressed AMCase. Chitin mediated alternative macrophage activation in
      vivo and the production of leukotriene B(4), which was required for optimal
      immune cell recruitment. Chitin is a recognition element for tissue infiltration
      by innate cells implicated in allergic and helminth immunity and this process can
      be negatively regulated by a vertebrate chitinase.

PMID- 17450128
TI  - Chemical biology: ignore the nonsense.

PMID- 17450127
TI  - A type III effector ADP-ribosylates RNA-binding proteins and quells plant
      immunity.
AB  - The bacterial plant pathogen Pseudomonas syringae injects effector proteins into
      host cells through a type III protein secretion system to cause disease. The
      enzymatic activities of most of P. syringae effectors and their targets remain
      obscure. Here we show that the type III effector HopU1 is a mono-ADP
      ribosyltransferase (ADP-RT). HopU1 suppresses plant innate immunity in a manner
      dependent on its ADP-RT active site. The HopU1 substrates in Arabidopsis thaliana
      extracts were RNA-binding proteins that possess RNA-recognition motifs (RRMs). A.
      thaliana knockout lines defective in the glycine-rich RNA-binding protein GRP7
      (also known as AtGRP7), a HopU1 substrate, were more susceptible than wild-type
      plants to P. syringae. The ADP-ribosylation of GRP7 by HopU1 required two
      arginines within the RRM, indicating that this modification may interfere with
      GRP7's ability to bind RNA. Our results suggest a pathogenic strategy where the
      ADP-ribosylation of RNA-binding proteins quells host immunity by affecting RNA
      metabolism and the plant defence transcriptome.

PMID- 17450129
TI  - Quantitative proteomic assessment of very early cellular signaling events.
AB  - Technical limitations have prevented proteomic analyses of events occurring less
      than 30 s after signal initiation. We developed an automated, continuous quench
      flow system allowing quantitative proteomic assessment of very early cellular
      signaling events (qPACE) with a time resolution of 1 s. Using this technique, we
      determined that autophosphorylation of the epidermal growth factor receptor
      occurs within 1 s after ligand stimulation and is followed rapidly by
      phosphorylation of the downstream signaling intermediates Src homologous and
      collagen-like protein and phospholipase C gamma 1.

PMID- 17450130
TI  - A high-quality catalog of the Drosophila melanogaster proteome.
AB  - Understanding how proteins and their complex interaction networks convert the
      genomic information into a dynamic living organism is a fundamental challenge in
      biological sciences. As an important step towards understanding the systems
      biology of a complex eukaryote, we cataloged 63% of the predicted Drosophila
      melanogaster proteome by detecting 9,124 proteins from 498,000 redundant and
      72,281 distinct peptide identifications. This unprecedented high proteome
      coverage for a complex eukaryote was achieved by combining sample diversity,
      multidimensional biochemical fractionation and analysis-driven experimentation
      feedback loops, whereby data collection is guided by statistical analysis of
      prior data. We show that high-quality proteomics data provide crucial information
      to amend genome annotation and to confirm many predicted gene models. We also
      present experimentally identified proteotypic peptides matching approximately 50%
      of D. melanogaster gene models. This library of proteotypic peptides should
      enable fast, targeted and quantitative proteomic studies to elucidate the systems
      biology of this model organism.

PMID- 17450131
TI  - Loss of Drosophila Myb interrupts the progression of chromosome condensation.
AB  - Completion of chromosome condensation is required before segregation during the
      mitotic cell cycle to ensure the transmission of genetic material with high
      fidelity in a timely fashion. In many eukaryotes this condensation is regulated
      by phosphorylation of histone H3 on Ser 10 (H3S10). This phosphorylation normally
      begins in the late-replicating pericentric heterochromatin and then spreads to
      the earlier replicating euchromatin. Here, we show that these phases of
      condensation are genetically separable in that the absence of Drosophila Myb
      causes cells to arrest with H3S10 phosphorylation of heterochromatin but not
      euchromatin. In addition, we used mosaic analysis to demonstrate that although
      the Myb protein can be removed in a single cell cycle, the failure of chromosome
      condensation occurs only after many cell divisions in the absence of Myb protein.
      The Myb protein is normally located in euchromatic but not heterochromatic
      regions of the nucleus, suggesting that Myb may be essential for a modification
      of euchromatin that is required for the efficient spread of chromosome
      condensation.

PMID- 17450132
TI  - pVHL and GSK3beta are components of a primary cilium-maintenance signalling
      network.
AB  - Defects in the structure or function of the primary cilium, an antennae-like
      structure whose functional integrity has been linked to the suppression of
      uncontrolled kidney epithelial cell proliferation, are a common feature of
      genetic disorders characterized by kidney cysts. However, the mechanisms by which
      primary cilia are maintained remain poorly defined. von Hippel-Lindau (VHL)
      disease is characterized by the development of premalignant renal cysts and
      arises because of functional inactivation of the VHL tumour suppressor gene
      product, pVHL. Here, we show that pVHL and glycogen synthase kinase (GSK)3beta
      are key components of an interlinked signalling pathway that maintains the
      primary cilium. Although inactivation of either pVHL or GSK3beta alone did not
      affect cilia maintenance, their combined inactivation leads to loss of cilia. In
      VHL patients, GSK3beta is subjected to inhibitory phosphorylation in renal cysts,
      but not in early VHL mutant lesions, and these cysts exhibit reduced frequencies
      of primary cilia. We propose that pVHL and GSK3beta function together in a
      ciliary-maintenance signalling network, disruption of which enhances the
      vulnerability of cells to lose their cilia, thereby promoting cyst formation.

PMID- 17450133
TI  - Dose-dependent oncogene-induced senescence in vivo and its evasion during mammary
      tumorigenesis.
AB  - Activating Ras mutations can induce either proliferation or senescence depending
      on the cellular context. To determine whether Ras activation has context
      dependent effects in the mammary gland, we generated doxycycline-inducible
      transgenic mice that permit Ras activation to be titrated. Low levels of Ras
      activation - similar to those found in non-transformed mouse tissues expressing
      endogenous oncogenic Kras2 - stimulate cellular proliferation and mammary
      epithelial hyperplasias. In contrast, high levels of Ras activation - similar to
      those found in tumours bearing endogenous Kras2 mutations - induce cellular
      senescence that is Ink4a-Arf- dependent and irreversible following Ras
      downregulation. Chronic low-level Ras induction results in tumour formation, but
      only after the spontaneous upregulation of activated Ras and evasion of
      senescence checkpoints. Thus, high-level, but not low-level, Ras activation
      activates tumour suppressor pathways and triggers an irreversible senescent
      growth arrest in vivo. We suggest a three-stage model for Ras-induced
      tumorigenesis consisting of an initial activating Ras mutation, overexpression of
      the activated Ras allele and, finally, evasion of p53-Ink4a-Arf-dependent
      senescence checkpoints.

PMID- 17450134
TI  - Introducing genetically encoded aldehydes into proteins.
AB  - Methods for introducing bioorthogonal functionalities into proteins have become
      central to protein engineering efforts. Here we describe a method for the site
      specific introduction of aldehyde groups into recombinant proteins using the 6
      amino-acid consensus sequence recognized by the formylglycine-generating enzyme.
      This genetically encoded 'aldehyde tag' is no larger than a His(6) tag and can be
      exploited for numerous protein labeling applications.

PMID- 17450135
TI  - Serotonin modulates the response of embryonic thalamocortical axons to netrin-1.
AB  - Modifying serotonin (5-HT) abundance in the embryonic mouse brain disrupts the
      precision of sensory maps formed by thalamocortical axons (TCAs), suggesting that
      5-HT influences their growth. We investigated the mechanism by which 5-HT
      influences TCAs during development. 5-HT(1B) and 5-HT(1D) receptor expression in
      the fetal forebrain overlaps with that of the axon guidance receptors DCC and
      Unc5c. In coculture assays, axons originating from anterior and posterior halves
      of the embryonic day 14.5 dorsal thalamus responded differently to netrin-1,
      reflecting the patterns of DCC and Unc5c expression. 5-HT converts the attraction
      exerted by netrin-1 on posterior TCAs to repulsion. Pharmacological manipulation
      of 5-HT(1B/1D) receptors and intracellular cAMP showed the signaling cascade
      through which this modulation occurs. An in vivo correlate of altered TCA
      pathfinding was obtained by transient manipulation of 5-HT(1B/1D) receptor
      expression abundance in the dorsal thalamus by in utero electroporation. These
      data demonstrate that serotonergic signaling has a previously unrecognized role
      in the modulation of axonal responsiveness to a classic guidance cue.

PMID- 17450136
TI  - Sniffing controls an adaptive filter of sensory input to the olfactory bulb.
AB  - Most sensory stimuli are actively sampled, yet the role of sampling behavior in
      shaping sensory codes is poorly understood. Mammals sample odors by sniffing, a
      complex behavior that controls odorant access to receptor neurons. Whether
      sniffing shapes the neural code for odors remains unclear. We addressed this
      question by imaging receptor input to the olfactory bulb of awake rats performing
      odor discriminations that elicited different sniffing behaviors. High-frequency
      sniffing of an odorant attenuated inputs encoding that odorant, whereas lower
      sniff frequencies caused little attenuation. Odorants encountered later in a
      sniff bout were encoded as the combination of that odorant and the background
      odorant during low-frequency sniffing, but were encoded as the difference between
      the two odorants during high-frequency sniffing. Thus, sniffing controls an
      adaptive filter for detecting changes in the odor landscape. These data suggest
      an unexpected functional role for sniffing and show that sensory codes can be
      transformed by sampling behavior alone.

PMID- 17450137
TI  - Medial prefrontal cell activity signaling prediction errors of action values.
AB  - To adapt behavior to a changing environment, one must monitor outcomes of
      executed actions and adjust subsequent actions accordingly. Involvement of the
      medial frontal cortex in performance monitoring has been suggested, but little is
      known about neural processes that link performance monitoring to performance
      adjustment. Here, we recorded from neurons in the medial prefrontal cortex of
      monkeys learning arbitrary action-outcome contingencies. Some cells
      preferentially responded to positive visual feedback stimuli and others to
      negative feedback stimuli. The magnitude of responses to positive feedback
      stimuli decreased over the course of behavioral adaptation, in correlation with
      decreases in the amount of prediction error of action values. Therefore, these
      responses in medial prefrontal cells may signal the direction and amount of error
      in prediction of values of executed actions to specify the adjustment in
      subsequent action selections.

PMID- 17450138
TI  - Detection and prediction of periodic patterns by the retina.
AB  - A fundamental task of the brain is detecting patterns in the environment that
      enable predictions about the future. Here, we show that the salamander and mouse
      retinas can recognize a wide class of periodic temporal patterns, such that a
      subset of ganglion cells fire strongly and specifically in response to a
      violation of the periodicity. This sophisticated retinal processing may provide a
      substrate for hierarchical pattern detection in subsequent circuits.

PMID- 17450139
TI  - Caenorhabditis elegans TRPA-1 functions in mechanosensation.
AB  - Members of the transient receptor potential (TRP) ion channel family mediate
      diverse sensory transduction processes in both vertebrates and invertebrates. In
      particular, members of the TRPA subfamily have distinct thermosensory roles in
      Drosophila, and mammalian TRPA1 is postulated to have a function in noxious cold
      sensation and mechanosensation. Here we show that mutations in trpa-1, the C.
      elegans ortholog of mouse Trpa1, confer specific defects in mechanosensory
      behaviors related to nose-touch responses and foraging. trpa-1 is expressed and
      functions in sensory neurons required for these mechanosensory behaviors, and
      contributes to neural responses of these cells to touch, particularly after
      repeated mechanical stimulation. Furthermore, mechanical pressure can activate C.
      elegans TRPA-1 heterologously expressed in mammalian cells. Collectively, these
      data demonstrate that trpa-1 encodes an ion channel that can be activated in
      response to mechanical pressure and is required for mechanosensory neuron
      function, suggesting a possible role in mechanosensory transduction or
      modulation.

PMID- 17450140
TI  - Modifiers of epigenetic reprogramming show paternal effects in the mouse.
AB  - There is increasing evidence that epigenetic information can be inherited across
      generations in mammals, despite extensive reprogramming both in the gametes and
      in the early developing embryo. One corollary to this is that disrupting the
      establishment of epigenetic state in the gametes of a parent, as a result of
      heterozygosity for mutations in genes involved in reprogramming, could affect the
      phenotype of offspring that do not inherit the mutant allele. Here we show that
      such effects do occur following paternal inheritance in the mouse. We detected
      changes to transcription and chromosome ploidy in adult animals. Paternal effects
      of this type have not been reported previously in mammals and suggest that the
      untransmitted genotype of male parents can influence the phenotype of their
      offspring.

PMID- 17450141
TI  - A six-nucleotide insertion-deletion polymorphism in the CASP8 promoter is
      associated with susceptibility to multiple cancers.
AB  - Caspases are important in the life and death of immune cells and therefore
      influence immune surveillance of malignancies. We tested whether genetic variants
      in CASP8, CASP10 and CFLAR, three genes important for death receptor-induced cell
      killing residing in tandem order on chromosome 2q33, are associated with cancer
      susceptibility. Using a haplotype-tagging SNP approach, we identified a six
      nucleotide deletion (-652 6N del) variant in the CASP8 promoter associated with
      decreased risk of lung cancer. The deletion destroys a stimulatory protein 1
      binding site and decreases CASP8 transcription. Biochemical analyses showed that
      T lymphocytes with the deletion variant had lower caspase-8 activity and
      activation-induced cell death upon stimulation with cancer cell antigens. Case
      control analyses of 4,995 individuals with cancer and 4,972 controls in a Chinese
      population showed that this genetic variant is associated with reduced
      susceptibility to multiple cancers, including lung, esophageal, gastric,
      colorectal, cervical and breast cancers, acting in an allele dose-dependent
      manner. These results support the hypothesis that genetic variants influencing
      immune status modify cancer susceptibility.

PMID- 17450142
TI  - Serotonin and neuropeptide F have opposite modulatory effects on fly aggression.
AB  - Both serotonin (5-HT) and neuropeptide Y have been shown to affect a variety of
      mammalian behaviors, including aggression. Here we show in Drosophila
      melanogaster that both 5-HT and neuropeptide F, the invertebrate homolog of
      neuropeptide Y, modulate aggression. We show that drug-induced increases of 5-HT
      in the fly brain increase aggression. Elevating 5-HT genetically in the
      serotonergic circuits recapitulates these pharmacological effects, whereas
      genetic silencing of these circuits makes the flies behaviorally unresponsive to
      the drug-induced increase of 5-HT but leaves them capable of aggression. Genetic
      silencing of the neuropeptide F (npf) circuit also increases fly aggression,
      demonstrating an opposite modulation to 5-HT. Moreover, this neuropeptide F
      effect seems to be independent of 5-HT. The implication of these two modulatory
      systems in fly and mouse aggression suggest a marked degree of conservation and a
      deep molecular root for this behavior.

PMID- 17450143
TI  - Origin of dendritic cells in peripheral lymphoid organs of mice.
AB  - Parabiosis experiments demonstrating that dendritic cells (DCs) do not
      equilibrate between mice even after prolonged joining by parabiosis have
      suggested that DCs are derived from self-renewing progenitors that divide in
      situ. However, here we found that unequal exchange of DCs between mice joined by
      parabiosis reflected uneven distribution of DC precursors in blood due to their
      short half-life in circulation. DCs underwent only a limited number of divisions
      in the spleen or lymph nodes over a 10- to 14-day period and were replenished
      from blood-borne precursors at a rate of nearly 4,300 cells per hour. Daughter
      DCs presented antigens captured by their progenitors, suggesting that DC division
      in peripheral lymphoid organs can prolong the duration of antigen presentation in
      vivo.

PMID- 17450144
TI  - Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper
      cells that produce interleukin 17.
AB  - The C-type lectin dectin-1 binds to yeast and signals through the kinase Syk and
      the adaptor CARD9 to induce production of interleukin 10 (IL-10) and IL-2 in
      dendritic cells (DCs). However, whether this pathway promotes full DC activation
      remains unclear. Here we show that dectin-1-Syk-CARD9 signaling induced DC
      maturation and the secretion of proinflammatory cytokines, including IL-6, tumor
      necrosis factor and IL-23, but little IL-12. Dectin-1-activated DCs 'instructed'
      the differentiation of CD4+ IL-17-producing effector T cells (T(H)-17 cells) in
      vitro, and a dectin-1 agonist acted as an adjuvant promoting the differentiation
      of T(H)-17 and T helper type 1 cells in vivo. Infection with Candida albicans
      induced CARD9-dependent T(H)-17 responses to the organism. Our data indicate that
      signaling through Syk and CARD9 can couple innate to adaptive immunity
      independently of Toll-like receptor signals and that CARD9 is required for the
      development of T(H)-17 responses to some pathogens.

PMID- 17450145
TI  - Strong isotropic flux pinning in solution-derived YBa2Cu3O7-x nanocomposite
      superconductor films.
AB  - Power applications of superconductors will be tremendously boosted if an
      effective method for magnetic flux immobilization is discovered. Here, we report
      the most efficient vortex-pinning mechanism reported so far which, in addition,
      is based on a low-cost chemical solution deposition technique. A dense array of
      defects in the superconducting matrix is induced in YBa(2)Cu(3)O(7-x)-BaZrO(3)
      nanocomposites where BaZrO(3) nanodots are randomly oriented. Non-coherent
      interfaces are the driving force for generating a new type of nanostructured
      superconductor. Angle-dependent critical-current measurements demonstrate that a
      strong and isotropic flux-pinning mechanism is extremely effective at high
      temperatures and high magnetic fields leading to high-temperature superconductors
      with record values of pinning force. The maximum vortex-pinning force achieved at
      65 K, 78 GN m(-3), is 500% higher than that of the best low-temperature NbTi
      superconductors at 4.2 K and so a great wealth of high-field applications will be
      possible at high temperatures.

PMID- 17450146
TI  - Highly ordered nanowire arrays on plastic substrates for ultrasensitive flexible
      chemical sensors.
AB  - The development of a robust method for integrating high-performance
      semiconductors on flexible plastics could enable exciting avenues in fundamental
      research and novel applications. One area of vital relevance is chemical and
      biological sensing, which if implemented on biocompatible substrates, could yield
      breakthroughs in implantable or wearable monitoring systems. Semiconducting
      nanowires (and nanotubes) are particularly sensitive chemical sensors because of
      their high surface-to-volume ratios. Here, we present a scalable and parallel
      process for transferring hundreds of pre-aligned silicon nanowires onto plastic
      to yield highly ordered films for low-power sensor chips. The nanowires are
      excellent field-effect transistors, and, as sensors, exhibit parts-per-billion
      sensitivity to NO2, a hazardous pollutant. We also use SiO2 surface chemistries
      to construct a 'nano-electronic nose' library, which can distinguish acetone and
      hexane vapours via distributed responses. The excellent sensing performance
      coupled with bendable plastic could open up opportunities in portable, wearable
      or even implantable sensors.

PMID- 17450147
TI  - Ligand interaction scan: a general method for engineering ligand-sensitive
      protein alleles.
AB  - The ligand interaction scan (LIScan) method is a general procedure for
      engineering small molecule ligand-regulated forms of a protein that is
      complementary to other 'reverse' genetic and chemical-genetic methods for drug
      target validation. It involves insertional mutagenesis by a chemical-genetic
      'switch', comprising a genetically encoded peptide module that binds with high
      affinity to a small-molecule ligand. We demonstrated the method with TEM-1 beta
      lactamase, using a tetracysteine hexapeptide insert and a biarsenical fluorescein
      ligand (FlAsH).

PMID- 17450148
TI  - A yeast two-hybrid smart-pool-array system for protein-interaction mapping.
AB  - We present here a new two-hybrid smart pool array (SPA) system in which, instead
      of individual activation domain strains, well-designed activation domain pools
      are screened in an array format that allows built-in replication and prey-bait
      deconvolution. Using this method, a Saccharomyces cerevisiae genome SPA increases
      yeast two-hybrid screening efficiency by an order of magnitude.

PMID- 17450149
TI  - Antielastin autoimmunity in tobacco smoking-induced emphysema.
AB  - Chronic obstructive pulmonary disease and emphysema are common destructive
      inflammatory diseases that are leading causes of death worldwide. Here we show
      that emphysema is an autoimmune disease characterized by the presence of
      antielastin antibody and T-helper type 1 (T(H)1) responses, which correlate with
      emphysema severity. These findings link emphysema to adaptive immunity against a
      specific lung antigen and suggest the potential for autoimmune pathology of other
      elastin-rich tissues such as the arteries and skin of smokers.

PMID- 17450150
TI  - The role of autophagy in cardiomyocytes in the basal state and in response to
      hemodynamic stress.
AB  - Autophagy, an evolutionarily conserved process for the bulk degradation of
      cytoplasmic components, serves as a cell survival mechanism in starving cells.
      Although altered autophagy has been observed in various heart diseases, including
      cardiac hypertrophy and heart failure, it remains unclear whether autophagy plays
      a beneficial or detrimental role in the heart. Here, we report that the cardiac
      specific loss of autophagy causes cardiomyopathy in mice. In adult mice,
      temporally controlled cardiac-specific deficiency of Atg5 (autophagy-related 5),
      a protein required for autophagy, led to cardiac hypertrophy, left ventricular
      dilatation and contractile dysfunction, accompanied by increased levels of
      ubiquitination. Furthermore, Atg5-deficient hearts showed disorganized sarcomere
      structure and mitochondrial misalignment and aggregation. On the other hand,
      cardiac-specific deficiency of Atg5 early in cardiogenesis showed no such cardiac
      phenotypes under baseline conditions, but developed cardiac dysfunction and left
      ventricular dilatation one week after treatment with pressure overload. These
      results indicate that constitutive autophagy in the heart under baseline
      conditions is a homeostatic mechanism for maintaining cardiomyocyte size and
      global cardiac structure and function, and that upregulation of autophagy in
      failing hearts is an adaptive response for protecting cells from hemodynamic
      stress.

PMID- 17450151
TI  - Distinct roles of HDAC complexes in promoter silencing, antisense suppression and
      DNA damage protection.
AB  - Histone acetylation is important in regulating DNA accessibility. Multifunctional
      Sin3 proteins bind histone deacetylases (HDACs) to assemble silencing complexes
      that selectively target chromatin. We show that, in fission yeast, an essential
      HDAC, Clr6, exists in two distinct Sin3 core complexes. Complex I contains an
      essential Sin3 homolog, Pst1, and other factors, and predominantly targets gene
      promoters. Complex II contains a nonessential Sin3 homolog, Pst2, and several
      conserved proteins. It preferentially targets transcribed chromosomal regions and
      centromere cores. Defects in complex II abrogate global protective functions of
      chromatin, causing increased accessibility of DNA to genotoxic agents and
      widespread antisense transcripts that are processed by the exosome. Notably, the
      two Clr6 complexes differentially repress forward and reverse centromeric repeat
      transcripts, suggesting that these complexes regulate transcription in
      heterochromatin and euchromatin in similar manners, including suppression of
      spurious transcripts from cryptic start sites.

PMID- 17450152
TI  - The structure of a polyQ-anti-polyQ complex reveals binding according to a linear
      lattice model.
AB  - Huntington and related neurological diseases result from expansion of a
      polyglutamine (polyQ) tract. The linear lattice model for the structure and
      binding properties of polyQ proposes that both expanded and normal polyQ tracts
      in the preaggregation state are random-coil structures but that an expanded polyQ
      repeat contains a larger number of epitopes recognized by antibodies or other
      proteins. The crystal structure of polyQ bound to MW1, an antibody against polyQ,
      reveals that polyQ adopts an extended, coil-like structure. Consistent with the
      linear lattice model, multimeric MW1 Fvs bind more tightly to longer than to
      shorter polyQ tracts and, compared with monomeric Fv, bind expanded polyQ repeats
      with higher apparent affinities. These results suggest a mechanism for the
      toxicity of expanded polyQ and a strategy to link anti-polyQ compounds to create
      high-avidity therapeutics.

PMID- 17450155
TI  - Complicated kinship in marmosets.

PMID- 17450153
TI  - Structural basis for Rab GTPase activation by VPS9 domain exchange factors.
AB  - RABEX-5 and other exchange factors with VPS9 domains regulate endocytic
      trafficking through activation of the Rab family GTPases RAB5, RAB21 and RAB22.
      Here we report the crystal structure of the RABEX-5 catalytic core in complex
      with nucleotide-free RAB21, a key intermediate in the exchange reaction pathway.
      The structure reveals how VPS9 domain exchange factors recognize Rab GTPase
      substrates, accelerate GDP release and stabilize the nucleotide-free
      conformation. We further identify an autoinhibitory element in a predicted
      amphipathic helix located near the C terminus of the VPS9 domain. The
      autoinhibitory element overlaps with the binding site for the multivalent
      effector RABAPTIN-5 and potently suppresses the exchange activity of RABEX-5.
      Autoinhibition can be partially reversed by mutation of conserved residues on the
      nonpolar face of the predicted amphipathic helix or by assembly of the complex
      with RABAPTIN-5.

PMID- 17450156
TI  - Getting to the heart of small RNAs.

PMID- 17450159
TI  - Validated alternatives: is immediate implementation required? Baluride: don't get
      taken for a ride.

PMID- 17450160
TI  - Validated alternatives: is immediate implementation required?

PMID- 17450161
TI  - Validated alternatives: is immediate implementation required? A word from USDA.

PMID- 17450162
TI  - Validated alternatives: is immediate implementation required? IACUC must review.

PMID- 17450163
TI  - Validated alternatives: is immediate implementation required? IACUC complacency.

PMID- 17450164
TI  - A firm, pea-shaped lesion on the paw of a beagle.

PMID- 17450166
TI  - Placement of canine and feline esophagostomy feeding tubes.
AB  - Esophagostomy feeding tubes may be used to provide nutrition to animals with
      insufficient calorie intake. This column describes tube placement and use in the
      feline patient.

PMID- 17450167
TI  - Refinement of intrathymic injection in mice.
AB  - Direct intrathymic injection is a common procedure used in several types of
      experimental protocols in the mouse. Currently available approaches involve major
      surgical procedures that expose the thoracic cavity, resulting in an increased
      risk of poor recovery and postsurgical complications. The authors sought to
      refine this surgery to reduce animal pain and distress without compromising
      overall efficiency of the technique. Using a minimally invasive method that does
      not expose the thoracic cavity, the authors gave accurately placed intrathymic
      injections, as confirmed by analyses with a reporter dye. They describe this new
      approach for intrathymic injection in mice that reduces complications associated
      with lengthy periods of anesthesia and thoracic cavity exposure.

PMID- 17450168
TI  - Airway management with the laryngeal tube in rabbits.
AB  - The rabbit's oropharyngeal anatomy complicates the use of endotracheal intubation
      for airway management during surgical procedures. To determine if the laryngeal
      tube is useful for airway management in rabbits, the authors applied the device
      and evaluated its efficacy to ventilate the lungs. The laryngeal tube was
      inserted blindly and without difficulty in six healthy male New Zealand White
      rabbits; all of the rabbits were ventilated adequately with and without
      neuromuscular blockade. The authors conclude that the laryngeal tube can be used
      as an alternative means of airway management in rabbits.

PMID- 17450169
TI  - Eradication of Helicobacter bilis and H. hepaticus from infected mice by using a
      medicated diet.
AB  - Infection of laboratory mice with Helicobacter spp. is a serious problem for many
      laboratory animal facilities worldwide. Rederivation and antibiotic treatment are
      two of the most common methods used to eliminate the bacterial infection from
      rodent colonies. Forty-seven newly imported mice were suspected to be positive
      for Helicobacter infection based on PCR analysis of pooled fecal samples from
      sentinel animals. We treated the mice with a medicated feed containing four
      antibiotic compounds (amoxicillin, clarithromycin, metronidazole, omeprazole).
      After eight weeks of continuous administration the animals were negative for H.
      bilis and H. hepaticus. Frequent retesting of the animals for up to one year
      proved that the mouse colony remained negative for Helicobacter spp.

PMID- 17450171
TI  - More PKA independent beta-adrenergic signalling via cAMP: is Rap1-mediated
      glucose uptake in vascular smooth cells physiologically important?
AB  - The proteome characterising a specific cell type makes up a unique intracellular
      signalling network and signalling has to be studied in a cell specific manner.
      Beta-adrenergic receptors are coupled to production of cAMP and PKA was initially
      believed to be the only protein activated by cAMP. However, cAMP-mediated
      signalling via Epac and Rap1 has emerged as an important contributor to cAMP
      signalling. In the current issue of the British Journal of Pharmacology, Kanda
      and Watanabe report that adrenaline stimulates glucose uptake in vascular smooth
      muscle cells. With pharmacological methods, supplemented with small interfering
      RNA against Rap1, the authors demonstrate that adrenaline increases glucose
      uptake via G(s), adenylate cyclase, cAMP and Rap1 activation. The authors could
      document neither PKA nor Epac as the receptor for cAMP mediating the effect.
      Although there is no doubt that Rap1 mediates adrenaline-stimulated glucose
      uptake in vascular smooth muscle cells, it may be too early to exclude PKA and
      Epac.

PMID- 17450170
TI  - Cannabinoids as therapeutic agents in cardiovascular disease: a tale of passions
      and illusions.
AB  - In addition to their classical known effects, such as analgesia, impairment of
      cognition and learning and appetite enhancement, cannabinoids have also been
      related to the regulation of cardiovascular responses and implicated in
      cardiovascular pathology. Elevated levels of endocannabinoids have been related
      to the extreme hypotension associated with various forms of shock as well as to
      the cardiovascular abnormalities that accompany cirrhosis. In contrast,
      cannabinoids have also been associated with beneficial effects on the
      cardiovascular system, such as a protective role in atherosclerosis progression
      and in cerebral and myocardial ischaemia. In addition, it has also been suggested
      that the pharmacological manipulation of the endocannabinoid system may offer a
      novel approach to antihypertensive therapy. During the last decades, the
      tremendous increase in the understanding of the molecular basis of cannabinoid
      activity has encouraged many pharmaceutical companies to develop more potent
      synthetic cannabinoid analogues and antagonists, leading to an explosion of basic
      research and clinical trials. Consequently. not only the synthetic THC dronabinol
      (Marinol) and the synthetic THC analogue nabilone (Cesamet) have been approved in
      the United States, but also the standardized cannabis extract (Sativex) in
      Canada. At least three strategies can be foreseen in the future clinical use of
      cannabinoid-based drugs: (a) the use of CB(1) receptor antagonists, such as the
      recently approved rimonabant (b) the use of CB(2)-selective agonists, and (c) the
      use of inhibitors of endocannabinoid degradation. In this context, the present
      review examines the effects of cannabinoids and of the pharmacological
      manipulation of the endocannabinoid system, in cardiovascular pathophysiology.

PMID- 17450172
TI  - Adrenaline increases glucose transport via a Rap1-p38MAPK pathway in rat vascular
      smooth muscle cells.
AB  - BACKGROUND AND PURPOSE: Adrenaline has been implicated in the pathogenesis of
      atherosclerosis. However, little is known regarding the role of adrenaline in
      glucose transport in VSMC. EXPERIMENTAL APPROACH: In this study, we examined the
      effects of adrenaline on glucose uptake in rat VSMC. We also examined the
      downstream signaling pathway from the beta-adrenoceptor to glucose uptake, using
      a pharmacological approach. To investigate the downstream action of adenylate
      cyclase, we studied the effects of GGTI-298, an inhibitor of geranylgeranylation
      of GTPases, including Rap1. To confirm the involvement of Rap1, we silenced Rap1
      by siRNA. KEY RESULTS: Adrenaline induced glucose uptake in a dose-dependent
      manner. The adrenaline-induced glucose uptake was inhibited by L-propranolol, (a
      selective beta-adrenoceptor antagonist), but not by prazosin (a selective
      alpha(1)-adrenoceptor antagonist) or UK14304 (a selective alpha(2)-adrenoceptor
      antagonist), suggesting the involvement of beta-adrenoceptors in glucose
      transport. Long-term treatment with cholera toxin, which resulted in
      sequestration of G(s) proteins, prevented the adrenaline-induced glucose uptake.
      Forskolin, a direct activator of adenylate cyclase, was found to mimic the
      effects of adrenaline. Adrenaline-induced glucose uptake was inhibited by GGTI
      298, not by H89 (a selective inhibitor of PKA). Silencing of Rap1 by siRNA
      attenuated the adrenaline-induced glucose uptake. Adrenaline-induced glucose
      uptake was inhibited by SB203580 (a selective inhibitor of p38MAPK) and
      adrenaline-induced p38MAPK activation was inhibited by GGTI-298 and siRNA against
      Rap1. CONCLUSIONS AND IMPLICATIONS: These findings suggest that adrenaline
      induced glucose transport is mediated by beta-adrenoceptors, G(s), adenylate
      cyclase, Rap1, and p38MAPK in vascular smooth muscle cells.

PMID- 17450173
TI  - Protective role of PI3-kinase-Akt-eNOS signalling pathway in intestinal injury
      associated with splanchnic artery occlusion shock.
AB  - BACKGROUND AND PURPOSE: Endothelial NO synthase (eNOS) is a dynamic enzyme
      tightly controlled by co- and post-translational lipid modifications,
      phosphorylation and regulated by protein-protein interactions. Here we have
      pharmacologically modulated the activation of eNOS, at different post
      translational levels, to assess the role of eNOS-derived NO and of these
      regulatory mechanisms in intestinal injury associated with splanchnic artery
      occlusion (SAO) shock. EXPERIMENTAL APPROACH: SAO shock was induced by clamping
      both the superior mesenteric artery and the celiac trunk for 45 min followed by
      30 min of reperfusion. During ischemia, 15 min prior to reperfusion, mice were
      given geldanamycin, an inhibitor of hsp90 recruitment to eNOS, or LY-294002 an
      inhibitor of phosphatidylinositol 3-kinase (PI3K), an enzyme that initiates Akt
      catalysed phosphorylation of eNOS on Ser1179. After 30 min of reperfusion,
      samples of ileum were taken for histological examination or for biochemical
      studies. KEY RESULTS: Either LY-294002 or geldanamycin reversed the increased
      activation of eNOS and Akt observed following SAO shock. These molecular effects
      were mirrored in vivo by an exacerbation of the intestinal damage. Histological
      damage also correlated with neutrophil infiltration, assessed as myeloperoxidase
      activity, and with an increased expression of the adhesion proteins: ICAM-I,
      VCAM, P-selectin and E-selectin. CONCLUSIONS AND IMPLICATIONS: Overall these
      results suggest that activation of the Akt pathway in ischemic regions of
      reperfused ileum is a protective event, triggered in order to protect the
      intestinal tissue from damage induced by ischaemia/reperfusion through a fine
      tuning of the endothelial NO pathway.

PMID- 17450174
TI  - Effects of methyl beta-cyclodextrin on EDHF responses in pig and rat arteries;
      association between SK(Ca) channels and caveolin-rich domains.
AB  - BACKGROUND AND PURPOSE: The small and intermediate conductance, Ca2+-sensitive K+
      channels (SK(Ca) and IK(Ca), respectively) which are pivotal in the EDHF pathway
      may be differentially activated. The importance of caveolae in the functioning of
      IK(Ca) and SK(Ca) channels was investigated. EXPERIMENTAL APPROACH: The effect of
      the caveolae-disrupting agent methyl-beta-cyclodextrin (MbetaCD) on IK(Ca) and
      SK(Ca) localization and function was determined. KEY RESULTS: EDHF-mediated,
      SK(Ca)-dependent myocyte hyperpolarizations evoked by acetylcholine in rat
      mesenteric arteries (following blockade of IK(Ca) with TRAM-34) were inhibited by
      MbetaCD. Hyperpolarizations evoked by direct SK(Ca) channel activation (using
      NS309 in the presence of TRAM-34) were also inhibited by MbetaCD, an effect
      reversed by cholesterol. In contrast, IK(Ca)-dependent hyperpolarizations (in the
      presence of apamin) were unaffected by MbetaCD. Similarly, in porcine coronary
      arteries, EDHF-mediated, SK(Ca)-dependent (but not IK(Ca)-dependent) endothelial
      cell hyperpolarizations evoked by substance P were inhibited by MbetaCD. In
      mesenteric artery homogenates subjected to sucrose-density centrifugation,
      caveolin-1 and SK3 (SK(Ca)) proteins but not IK1 (IK(Ca)) protein migrated to the
      buoyant, caveolin-rich fraction. MbetaCD pretreatment redistributed caveolin-1
      and SK3 proteins into more dense fractions. In immunofluorescence images of
      porcine coronary artery endothelium, SK3 (but not IK1) and caveolin-1 were co
      localized. Furthermore, caveolin-1 immunoprecipitates prepared from native
      porcine coronary artery endothelium contained SK3 but not IK1 protein.
      CONCLUSIONS AND IMPLICATIONS: These data provide strong evidence that endothelial
      cell SK(Ca) channels are located in caveolae while the IK(Ca) channels reside in
      a different membrane compartment. These studies reveal cellular organisation as a
      further complexity in the EDHF pathway signalling cascade.

PMID- 17450175
TI  - Stem-cell niches: nursery rhymes across kingdoms.
AB  - Despite the large evolutionary distance between the plant and animal kingdoms,
      stem cells in both reside in specialized cellular contexts called stem-cell
      niches. Although stem-cell-specification factors have been recruited from plant
      specific gene families, maintenance factors that repress stem-cell
      differentiation are conserved between plants and animals. Recent evidence
      indicates that stem cells in multicellular organisms can be specified by kingdom
      specific patterning mechanisms that connect to a related core of epigenetic stem
      cell factors.

PMID- 17450176
TI  - The emerging shape of the ESCRT machinery.
AB  - The past two years have seen an explosion in the structural understanding of the
      endosomal sorting complex required for transport (ESCRT) machinery that
      facilitates the trafficking of ubiquitylated proteins from endosomes to lysosomes
      via multivesicular bodies (MVBs). A common organization of all ESCRTs is a rigid
      core attached to flexibly connected modules that recognize other components of
      the MVB pathway. Several previously unsuspected key links between multiple ESCRT
      subunits, phospholipids and ubiquitin have now been elucidated, which, together
      with the detailed morphological analyses of ESCRT-depletion phenotypes, provide
      new insights into the mechanism of MVB biogenesis.

PMID- 17450177
TI  - Werner and Hutchinson-Gilford progeria syndromes: mechanistic basis of human
      progeroid diseases.
AB  - Progeroid syndromes have been the focus of intense research in part because they
      might provide a window into the pathology of normal ageing. Werner syndrome and
      Hutchinson-Gilford progeria syndrome are two of the best characterized human
      progeroid diseases. Mutated genes that are associated with these syndromes have
      been identified, mouse models of disease have been developed, and molecular
      studies have implicated decreased cell proliferation and altered DNA-damage
      responses as common causal mechanisms in the pathogenesis of both diseases.

PMID- 17450178
TI  - Successful second cord blood transplantation using fludarabine and
      cyclophosphamide as a preparative regimen for graft rejection following reduced
      intensity cord blood transplantation.

PMID- 17450180
TI  - Treatment schedules for 5-HT2A blocking in progressive multifocal
      leukoencephalopathy using risperidone or ziprasidone.

PMID- 17450181
TI  - Graft-versus-tumour effect in refractory metastatic neuroblastoma.

PMID- 17450179
TI  - Successful allogeneic stem cell transplantation in second chronic-phase CML
      induced by the tyrosine kinase inhibitor nilotinib (AMN107) after blast crisis
      under imatinib.

PMID- 17450182
TI  - Efficient mobilization of peripheral blood stem cells following CAD chemotherapy
      and a single dose of pegylated G-CSF in patients with multiple myeloma.
AB  - High-dose chemotherapy followed by autologous blood stem cell transplantation is
      the standard treatment for myeloma patients. In this study, CAD
      (cyclophosphamide, adriamycin, dexamethasone) chemotherapy and a single dose of
      pegfilgrastim (12 mg) was highly effective in mobilizing peripheral blood stem
      cells (PBSCs) for subsequent transplantation, with 88% of patients (n = 26)
      achieving the CD34+ cell harvest target of > or = 7.50 x 10(6) CD34+ cells/kg
      body weight, following a median of two apheresis procedures (range 1-4) and with
      first apheresis performed at a median day 13 after CAD application (range 10-20).
      Patients treated with pegfilgrastim showed a reduced time to first apheresis
      procedure from mobilization compared with filgrastim-mobilized historical matched
      controls (n = 52, P = 0.015). The pegfilgrastim mobilization regimen allowed for
      transplantation of a median of 3.58 x 10(6) CD34+ cells/kg body weight while
      leaving sufficient stored cells for a second high-dose regimen and back-ups in
      most patients. Engraftment following transplantation was comparable to
      filgrastim, with a median time of 14 days to leucocyte > or =1.0 x 10(9)/l (range
      10-21) and 11 days to platelets > or = 20 x 10(9)/l (range 0-15). The results of
      this study thus provide further support for the clinical utility of pegfilgrastim
      for the mobilization of PBSC following chemotherapy in cancer patients scheduled
      for transplantation.

PMID- 17450183
TI  - Fludarabine and cyclophosphamide based reduced intensity conditioning (RIC)
      regimens reduce rejection and improve outcome in Indian patients undergoing
      allogeneic stem cell transplantation for severe aplastic anemia.
AB  - Thirty-five patients (25 men and 10 women) with a median age of 20 years with
      severe aplastic anaemia (SAA) underwent HLA identical stem cell transplantation
      (HSCT) using a combination of fludarabine and cyclophosphamide +/- anti-thymocyte
      globulin between 2004 and 2006. Cyclosporine and mini methotrexate were used as
      GVHD prophylaxis. Graft source included peripheral blood stem cells (28) or G-CSF
      stimulated bone marrow (7). Two patients expired < 7 days post-HSCT while 32
      (91.5%) patients engrafted with a median neutrophil and platelet engraftment time
      of 12 days each. Three patients (8.5%) developed veno-occlusive disease while
      acute GVHD occurred in 29% of evaluable patients, with chronic GVHD in 32%. At a
      mean follow-up of 22 months, 29 (82.8%) are alive and well. When compared with 26
      patients previously transplanted using Cy200/antilymphocyte globulin, there was
      faster neutrophil engraftment (12 vs 16 days; P = 0.002) with significantly lower
      rejection rates (2.9 vs 30.7%; P = 0.003) and a superior event-free (82.8 vs
      38.4%; P = 0.001) and overall survival (82.8 vs 46.1%; P = 0.005). A combination
      of fludarabine with cyclophosphamide +/- anti-thymocyte globulin reduces
      rejection and improves overall and event-free survival in Indian patients
      undergoing HSCT for severe aplastic anaemia.

PMID- 17450184
TI  - Viral purging of haematological autografts: should we sneeze on the graft?
AB  - High-dose cytotoxic chemotherapy followed by autologous haematopoietic stem cell
      transplantation (ASCT) is extensively used for the treatment of many
      haematopoietic, as well as several epithelial cancers. Disease relapse may be the
      result of tumour contamination within autograft as evidenced by gene marking
      studies. The multiple purging strategies that have been described to date have
      not proven effective in most ASCT settings. This review addresses the possibility
      of using oncolytic viruses as a novel purging strategy. DNA viruses such as
      genetically engineered adenoviral vectors have widely been used to deliver either
      a prodrug-activating enzyme or express wild-type p53 selectively in tumour cells
      in ex vivo purging protocols. In addition, conditionally replicating adenoviruses
      that selectively replicate in tumour cells and herpes simplex virus type 1 are
      other DNA viruses that have been tested as ex vivo purging agents under
      laboratory conditions. Vesicular stomatitis virus (VSV) and reovirus are
      naturally occurring RNA viruses that appear to hold promise as purging agents
      under ex vivo and in vivo settings. Preclinical data demonstrate reovirus's
      purging potential against breast, monocytic and myeloma cell lines as well as
      patient-derived tumours of diffuse large B-cell lymphoma, chronic lymphocytic
      leukaemia, Waldenstrom macroglobulinemia and small lymphocytic lymphoma. In
      addition, VSV has shown effective killing of leukaemic cell lines and multiple
      myeloma patient specimens. Given the increasing interest in the utilization of
      viruses as purging agents, the following review provides a timely summary of the
      potential and the challenges of oncolytic viruses as purging modalities during
      ASCT.

PMID- 17450185
TI  - Long term disease-free survival in acute leukemia patients recovering with
      increased gammadelta T cells after partially mismatched related donor bone marrow
      transplantation.
AB  - Allogeneic stem cell transplantation (ASCT) has improved leukemia-free survival
      (LFS) in many but not all patients with acute leukemia. This is an eight-year
      follow-up to our previous study showing a survival advantage to patients with an
      increased gammadelta T cells following ASCT. gammadelta T cell levels were
      collected prospectively in 153 patients (acute lymphoblastic leukemia (ALL) n =
      77; acute myelogenous leukemia (AML) n = 76) undergoing partially mismatched
      related donor ASCT. Median age was 22 years (1-59), and 62% of the patients were
      in relapse at transplant. Patient-donor human leukocyte antigen (HLA) disparity
      of three antigens was 37% in the graft-versus-host disease (GvHD) and 29% in the
      rejection directions. All patients received a partially T cell-depleted graft
      using T10B9 (n = 46) or OKT3 (n = 107). Five years LFS and overall survival (OS)
      of patients with increased gammadelta compared to those with normal/decreased
      numbers were 54.4 vs 19.1%; P < 0.0003, and 70.8 vs 19.6% P < 0.0001,
      respectively, with no difference in GvHD (P = 0.96). In a Cox multivariate
      analysis, normal/decreased gammadelta (hazard ratio (HR) 4.26, P = 0.0002) and
      sex mismatch (HR 1.45 P=0.049) were associated with inferior LFS. In conclusion,
      gammadelta T cells may facilitate a graft-versus-leukemia (GvL) effect, without
      causing GvHD. Further evaluations of this effect may lead to specific
      immunotherapy for patients with refractory leukemia.

PMID- 17450186
TI  - Overview of Cancer Control Research in Korean Americans.
AB  - Eighteen noteworthy manuscripts published between 1995 and 2002 were found in a
      literature search under the terms "Koreans" and "cancer." These articles cover a
      variety of subjects, from specific cancers to screening behaviors to religious
      and cultural influences, all of which should be considered in developing
      prevention and screening strategies.

PMID- 17450187
TI  - Asian and Pacific Islander Special Populations Network.
AB  - This paper briefly describes four programs within the National Cancer Institute's
      Special Populations Network, programs designed to promote cancer awareness in
      minority and underserved populations. These four programs are dedicated to issues
      involving Asian Americans and Pacific Islanders. Of particular interest is the
      fact that they each have a strong community focus and are targeted to specific
      populations.

PMID- 17450188
TI  - Condition-specific competition in container mosquitoes: the role of noncompeting
      life-history stages.
AB  - Condition-specific competition, wherein competitive superiority varies with the
      abiotic environment, can determine species' distributions in a spatially
      heterogeneous environment. We investigated this phenomenon with two competing
      container-dwelling mosquitoes. We tested the hypothesis that habitat drying
      alters the outcome of interspecific competition, predicting that the competitive
      impact of Aedes albopictus on Aedes aegypti would be severe in wetter
      environments, but greatly reduced in drier environments. We tested these
      predictions in a laboratory experiment within cages, with aquatic larvae residing
      in water-filled cups within the cage, and adults emerging within the cage and
      ovipositing on the cups. We raised each species alone or with the competitor.
      Environmental treatments were fluctuating (water in cups evaporated to 50% of the
      original volume and then cups were refilled), and drying (water in cups
      evaporated completely and cups remained dry for two weeks before refilling).
      There was a significant interaction between treatment and species combination for
      adult populations of both species. Interspecific competition was highly
      asymmetrical. In the wetter fluctuating environment, interspecific competition
      had a large negative effect on A. aegypti, but in the drying environment,
      interspecific competition had a large negative effect on A. albopictus, and
      relatively little impact on A. aegypti. The main cause of the shift in
      competitive advantage appeared to be a greater increase in egg mortality for A.
      albopictus under dry conditions, compared to A. aegypti. Thus, mortality
      impinging on noncompeting life cycle stages can alter the population level impact
      of interspecific competition. The hypothesis that dry conditions shift
      competitive advantage away from A. albopictus is supported in this experiment.

PMID- 17450189
TI  - Climate change: healthy solutions.

PMID- 17450190
TI  - A new venue for the Director's Perspective.

PMID- 17450192
TI  - Risk of lymphohematopoietic malignancies in uranium miners.

PMID- 17450193
TI  - Ozone and semen quality.

PMID- 17450196
TI  - Fetal lead exposure and infant mental development index.

PMID- 17450197
TI  - Red tide chokehold.

PMID- 17450198
TI  - Mining for glyceollins.

PMID- 17450200
TI  - Pesticides: toxic legacy.

PMID- 17450201
TI  - New voice for the environment.

PMID- 17450203
TI  - Children's health centers: past, present, and future.

PMID- 17450204
TI  - Ragweed subpollen particles reach deep into lungs.

PMID- 17450205
TI  - Beyond the bench: healthy home, healthy community.

PMID- 17450206
TI  - Driven to extremes health effects of climate change.

PMID- 17450207
TI  - A changing climate of litigation.

PMID- 17450208
TI  - Solar thrill: using the sun to cool vaccines.

PMID- 17450213
TI  - Using nutrition for intervention and prevention against environmental chemical
      toxicity and associated diseases.
AB  - BACKGROUND: Nutrition and lifestyle are well-defined modulators of chronic
      diseases. Poor dietary habits (such as high intake of processed foods rich in fat
      and low intake of fruits and vegetables), as well as a sedentary lifestyle
      clearly contribute to today's compromised quality of life in the United States.
      It is becoming increasingly clear that nutrition can modulate the toxicity of
      environmental pollutants. OBJECTIVES: Our goal in this commentary is to discuss
      the recommendation that nutrition should be considered a necessary variable in
      the study of human disease associated with exposure to environmental pollutants.
      DISCUSSION: Certain diets can contribute to compromised health by being a source
      of exposure to environmental toxic pollutants. Many of these pollutants are fat
      soluble, and thus fatty foods often contain higher levels of persistent organics
      than does vegetable matter. Nutrition can dictate the lipid milieu, oxidative
      stress, and antioxidant status within cells. The modulation of these parameters
      by an individual's nutritional status may have profound affects on biological
      processes, and in turn influence the effects of environmental pollutants to cause
      disease or dysfunction. For example, potential adverse health effects associated
      with exposure to polychlorinated biphenyls may increase as a result of ingestion
      of certain dietary fats, whereas ingestion of fruits and vegetables, rich in
      antioxidant and anti-inflammatory nutrients or bioactive compounds, may provide
      protection. CONCLUSIONS: We recommend that future directions in environmental
      health research explore this nutritional paradigm that incorporates a
      consideration of the relationships between nutrition and lifestyle, exposure to
      environmental toxicants, and disease. Nutritional interventions may provide the
      most sensible means to develop primary prevention strategies of diseases
      associated with many environmental toxic insults.

PMID- 17450214
TI  - Biodiesel exhaust: the need for health effects research.
AB  - BACKGROUND: Biodiesel is a diesel fuel alternative that has shown potential of
      becoming a commercially accepted part of the United States' energy
      infrastructure. In November 2004, the signing of the Jobs Creation Bill HR 4520
      marked an important turning point for the future production of biodiesel in the
      United States because it offers a federal excise tax credit. By the end of 2005,
      industry production was 75 million gallons, a 300% increase in 1 year. Current
      industry capacity, however, stands at just over 300 million gallons/year, and
      current expansion and new plant construction could double the industry's capacity
      within a few years. Biodiesel exhaust emission has been extensively characterized
      under field and laboratory conditions, but there have been limited cytotoxicity
      and mutagenicity studies on the effects of biodiesel exhaust in biologic systems.
      OBJECTIVES: We reviewed pertinent medical literature and addressed
      recommendations on testing specific research needs in the field of biodiesel
      toxicity. DISCUSSION: Employment of biodiesel fuel is favorably viewed, and there
      are suggestions that its exhaust emissions are less likely to present any risk to
      human health relative to petroleum diesel emissions. CONCLUSION: The speculative
      nature of a reduction in health effects based on chemical composition of
      biodiesel exhaust needs to be followed up with investigations in biologic
      systems.

PMID- 17450215
TI  - Hormesis and its place in nonmonotonic dose-response relationships: some
      scientific reality checks.
AB  - OBJECTIVE: This analysis is a critical assessment of current hormesis literature.
      I discuss definitions, characterization, generalizability, mechanisms, absence of
      empirical data specific for hormesis hypothesis testing, and arguments that
      hormesis be the "default assumption" in risk assessment. DATA SOURCES: Hormesis,
      a biological phenomenon typically described as low-dose stimulation from
      substances producing higher-dose inhibition, has recently garnered interest in
      several quarters. The principal sources of published materials for this analysis
      are the writings of certain proponents of hormesis. Surprisingly few systematic
      critiques of current hormesis literature exist. Limits to the phenomenon's
      appropriate role in risk assessment and health policy have been published. DATA
      SYNTHESIS: Serious gaps in scientific understanding remain: a stable definition;
      generalizability, especially for humans; a clear mechanistic basis; limitations
      in the presence of multiple toxic end points, target organs, and mechanisms.
      Absence of both arms-length, consensus-driven, scientific evaluations and
      empirical data from studies specifically designed for hormesis testing have
      limited its acceptance. CONCLUSIONS: Definition, characterization, occurrence,
      and mechanistic rationale for hormesis will remain speculative, absent rigorous
      studies done specifically for hormesis testing. Any role for hormesis in current
      risk assessment and regulatory policies for toxics remains to be determined.

PMID- 17450216
TI  - Ambient and microenvironmental particles and exhaled nitric oxide before and
      after a group bus trip.
AB  - OBJECTIVES: Airborne particles have been linked to pulmonary oxidative stress and
      inflammation. Because these effects may be particularly great for traffic-related
      particles, we examined associations between particle exposures and exhaled nitric
      oxide (FE(NO)) in a study of 44 senior citizens, which involved repeated trips
      aboard a diesel bus. METHODS: Samples of FE(NO) collected before and after the
      trips were regressed against microenvironmental and ambient particle
      concentrations using mixed models controlling for subject, day, trip, vitamins,
      collection device, mold, pollen, room air nitric oxide, apparent temperature, and
      time to analysis. Although ambient concentrations were collected at a fixed
      location, continuous group-level personal samples characterized
      microenvironmental exposures throughout facility and trip periods. RESULTS: In
      pre-trip samples, both microenvironmental and ambient exposures to fine particles
      were positively associated with FE(NO). For example, an interquartile increase of
      4 microg/m(3) in the daily microenvironmental PM(2.5) concentration was
      associated with a 13% [95% confidence interval (CI), 2-24%) increase in FE(NO).
      After the trips, however, FE(NO) concentrations were associated pre-dominantly
      with microenvironmental exposures, with significant associations for
      concentrations measured throughout the whole day. Associations with exposures
      during the trip also were strong and statistically significant with a 24% (95%
      CI, 15-34%) increase in FE(NO) predicted per interquartile increase of 9
      microg/m(3) in PM(2.5). Although pre-trip findings were generally robust, our
      post-trip findings were sensitive to several influential days. CONCLUSIONS: Fine
      particle exposures resulted in increased levels of FE(NO) in elderly adults,
      suggestive of increased airway inflammation. These associations were best
      assessed by microenvironmental exposure measurements during periods of high
      personal particle exposures.

PMID- 17450217
TI  - Cyclooxygenase-2 induction by arsenite through the IKKbeta/NFkappaB pathway
      exerts an antiapoptotic effect in mouse epidermal Cl41 cells.
AB  - BACKGROUND: Arsenic contamination has become a major public health concern
      worldwide. Epidemiologic data show that long-term arsenic exposure results in the
      risk of skin cancer. However, the mechanisms underlying carcinogenic effects of
      arsenite on skin remain to be studied. OBJECTIVES: In the present study we
      evaluated cyclooxygenase-2 (COX-2) expression, the signaling pathways leading to
      COX-2 induction, and its antiapoptotic function in the response to arsenite
      exposure in mouse epidermal JB6 Cl41 cells. METHODS: We used the luciferase
      reporter assay and Western blots to determine COX-2 induction by arsenite. We
      utilized dominant negative mutant, genetic knockout, gene knockdown, and gene
      overexpression approaches to elucidate the signaling pathway involved in COX-2
      induction and its protective effect on cell apoptosis. RESULTS: The induction of
      COX-2 by arsenite was inhibited in Cl41 cells transfected with IKKbeta-KM, a
      dominant mutant inhibitor of kbeta (Ikbeta) kinase (IKKbeta), and in IKKbeta
      knockout (IKKbeta(-/-)) mouse embryonic fibroblasts (MEFs). IKKbeta/nuclear
      factor kappaB (NFkappaB) pathway-mediated COX-2 induction exerted an
      antiapoptotic effect on the cells exposed to arsenite because cell apoptosis was
      significantly enhanced in the Cl41 cells transfected with IKKbeta-KM or COX-2
      small interference RNA (siCOX-2). In addition, IKKbeta(-/-) MEFs stably
      transfected with COX-2 showed more resistance to arsenite-induced apoptosis
      compared with the same control vector-transfected cells. CONCLUSIONS: These
      results demonstrate that arsenite exposure can induce COX-2 expression through
      the IKKbeta/NFkappaB pathway, which thereby exerts an antiapoptotic effect in
      response to arsenite. In light of the importance of apoptosis evasion during
      carcinogenesis, we anticipate that COX-2 induction may be at least partially
      responsible for the carcinogenic effect of arsenite on skin.

PMID- 17450218
TI  - Proton magnetic resonance spectroscopic evidence of glial effects of cumulative
      lead exposure in the adult human hippocampus.
AB  - BACKGROUND: Exposure to lead is known to have adverse effects on cognition in
      several different populations. Little is known about the underlying structural
      and functional correlates of such exposure in humans. OBJECTIVES: We assessed the
      association between cumulative exposure to lead and levels of different brain
      metabolite ratios in vivo using magnetic resonance spectroscopy (MRS). METHODS:
      We performed MRS on 15 men selected from the lowest quintile of patella bone lead
      within the Department of Veterans Affairs' Normative Aging Study (NAS) and 16
      from the highest to assess in the hippocampal levels of the metabolites N
      acetylaspartate, myoinositol, and choline, each expressed as a ratio with
      creatine. Bone lead concentrations-indicators of cumulative lead exposure-were
      previously measured using K-X-ray fluorescence spectroscopy. MRS was performed on
      the men from 2002 to 2004. RESULTS: A 20-microg/g bone and 15-microg/g bone
      higher patella and tibia bone lead concentration--the respective interquartile
      ranges within the whole NAS--were associated with a 0.04 [95% confidence interval
      (CI), 0.00-0.08; p = 0.04] and 0.04 (95% CI, 0.00-0.08; p = 0.07) higher
      myoinositol-to-creatine ratio in the hippocampus. After accounting for patella
      bone lead declines over time, analyses adjusted for age showed that the effect of
      a 20-microg/g bone higher patella bone lead level doubled (0.09; 95% CI, 0.01
      0.17; p = 0.03). CONCLUSIONS: Cumulative lead exposure is associated with an
      increase in the myinositol-to-creatine ratio. These data suggest that, as
      assessed with MRS, glial effects may be more sensitive than neuronal effects as
      an indicator of cumulative exposure to lead in adults.

PMID- 17450219
TI  - Air pollution and mortality in Chile: susceptibility among the elderly.
AB  - OBJECTIVE: The estimated mortality rate associated with ambient air pollution
      based on general population studies may not be representative of the effects on
      certain subgroups. The objective of the present study was to determine the
      influence of relatively high concentrations of air pollution on mortality in a
      general population sample and in the very elderly. STUDY DESIGN: Daily time
      series analyses tested the association between daily air pollution and daily
      mortality in seven Chilean urban centers during 1997-2003. Results were adjusted
      for day of the week and humidex. RESULTS: Daily averaged particulate matter with
      aerodynamic matter < 10 microm (PM(10)) was 84.88 microg/m(3), sulfur dioxide was
      14.08 ppb, and carbon monoxide was 1.29 ppb. The 1-hr maximum ozone was 100.13
      ppb. The percentage increases in nonaccidental mortality associated with an
      increase in PM(10) equivalent to its mean were 4.53 (t-ratio 1.52) for those < 65
      years and 14.03 (3.87) for those > 85 years. Respective values were 4.96 (1.17)
      and 8.56 (2.02) for O(3); 4.77 (2.50) and 7.92 (3.23) for SO(2); and 4.10 (2.52)
      and 8.58 (4.45) for CO. CONCLUSION: Our results suggest that the very elderly are
      particularly susceptible to dying from air pollution. Concentrations deemed
      acceptable for the general population may not adequately protect the very
      elderly.

PMID- 17450220
TI  - Mortality among pesticide applicators exposed to chlorpyrifos in the Agricultural
      Health Study.
AB  - BACKGROUND: Chlorpyrifos is one of the most widely used organophosphate
      insecticides in the United States. Although the toxicity of chlorpyrifos has been
      extensively studied in animals, the epidemiologic data are limited. OBJECTIVE: To
      evaluate whether agricultural chlorpyrifos exposure was associated with
      mortality, we examined deaths among pesticide applicators in the Agricultural
      Health Study, a prospective study of licensed pesticide applicators in Iowa and
      North Carolina. METHODS: A total of 55,071 pesticide applicators were included in
      this analysis. Detailed pesticide exposure data and other information were
      obtained from self-administered questionnaires completed at the time of
      enrollment (1993-1997). Lifetime chlorpyrifos use was divided into tertiles.
      Poisson regression analysis was used to evaluate the exposure-response
      relationships between chlorpyrifos use and causes of death after adjustment for
      potential confounders. RESULTS: A total of 1,851 deaths (588 among chlorpyrifos
      users) were observed during the study period, 1993-2001. The relative risk (RR)
      of death from all causes combined among applicators exposed to chlorpyrifos was
      slightly lower than that for nonexposed applicators (RR = 0.90; 95% confidence
      interval, 0.81-1.01). For most causes of death analyzed, there was no evidence of
      an exposure-response relationship. However, the relative risks for mortality from
      suicide and non-motor-vehicle accidents were increased 2-fold in the highest
      category of chlorpyrifos exposure days. CONCLUSIONS: Our findings of a possible
      association between chlorpyrifos use and external causes of death were based on
      small numbers. However, the findings may reflect a link between chlorpyrifos and
      depression or other neurobehavioral symptoms that deserves further evaluation.

PMID- 17450221
TI  - Up-regulation of tissue factor in human pulmonary artery endothelial cells after
      ultrafine particle exposure.
AB  - BACKGROUND: Epidemiology studies have linked exposure to pollutant particles to
      increased cardiovascular mortality and morbidity, but the mechanisms remain
      unknown. OBJECTIVES: We tested the hypothesis that the ultrafine fraction of
      ambient pollutant particles would cause endothelial cell dysfunction. METHODS: We
      profiled gene expression of human pulmonary artery endothelial cells (HPAEC)
      exposed to ultrafine particles (UFPs; 100 microg/mL) from Chapel Hill, North
      Carolina, or vehicle for 4 hr with Affymetrix HG U133 Plus 2.0 chips (n = 4
      each). RESULTS: We found 320 up-regulated genes and 106 down-regulated genes (p <
      0.01, 5% false discovery rate). We noted up-regulation of genes related to
      coagulation [tissue factor (F3) and coagulation factor II receptor-like 2
      (F2RL2)] and differential regulation of genes related to F3 signaling (FOS, JUN,
      and NFKBIA). Results of quantitative polymerase chain reaction show a significant
      up-regulation of F3 after 10 and 100 microg/mLUFP exposures. Additionally, the
      water-soluble fractions of UFPs were sufficient to induce the expression of F3,
      F2RL2, and heme oxygenase 1 (HMOX1). Treatment of HPAEC with UFPs for 16 hr
      increased the release of interleukin (IL)-6 and IL-8. Pretreatment of HPAEC with
      a blocking antibody against F3 attenuated IL-6 and IL-8 release by 30 and 70%,
      respectively. CONCLUSIONS: Using gene profiling, we discovered that UFPs may
      induce vascular endothelial cells to express genes related to clotting. These
      results indicate that PM may cause adverse cardiovascular health effects by
      activating coagulation-inflammation circuitry.

PMID- 17450222
TI  - Mammary gland development as a sensitive end point after acute prenatal exposure
      to an atrazine metabolite mixture in female Long-Evans rats.
AB  - BACKGROUND: Atrazine (ATR), a widely used chlorotriazine herbicide, inhibits a
      number of endocrine-dependent processes, including gonadotrophin surges and
      mammary gland development in rats. Chlorotriazine herbicides are rapidly
      metabolized in plants and animals to form a group of metabolites that are
      detected both in the environment and in exposed animals. The extent to which
      these metabolites are responsible directly for the observed health effects is not
      understood. OBJECTIVES: Our goal was to determine if a mixture of ATR
      metabolites, in proportions found in the environment, might produce developmental
      effects in Long-Evans rats following exposure late in pregnancy. METHODS: We
      administered an ATR metabolite mixture (AMM) containing ATR, hydroxyatrazine,
      diaminochlorotriazine, deethylatrazine, and deisopropylatrazine orally to
      pregnant Long-Evans rats at 0.09, 0.87, or 8.73 mg/kg body weight (bw)/day, on
      gestation days 15-19, using 0 and 100 mg ATR/kg bw/day as negative and positive
      controls, respectively. RESULTS: We observed no significant effect of acute AMM
      exposure on body weight gain in dams during the dosing period, weight loss in
      pups on postnatal day (PND)4, or pubertal timing, as is seen with ATR alone.
      However, as with ATR, we detected delayed mammary gland development, evaluated by
      whole mount analysis, as early as PND4 in all treatment groups. CONCLUSIONS: Our
      data suggest that acute exposure to AMM at levels as low as 0.09 mg/kg bw during
      late pregnancy causes persistent alterations in mammary gland development of
      female offspring, and that these effects do not appear to be related to bw or
      associated with pubertal timing.

PMID- 17450223
TI  - In utero exposure to environmental tobacco smoke potentiates adult responses to
      allergen in BALB/c mice.
AB  - BACKGROUND: Fetal stress has been linked to adult atherosclerosis, obesity, and
      diabetes. Epidemiology studies have associated fetal exposure to maternal smoking
      and postnatal exposure to environmental tobacco smoke (ETS) with increased asthma
      risk. OBJECTIVE: We tested the hypothesis, in a mouse model of asthma, that in
      utero ETS exposure alters airway function and respiratory immune responses in
      adults. METHODS: Pregnant Balb/c mice were exposed daily to ETS or HEPA-filtered
      air (AIR). Offspring inhaled aerosolized ovalbumin (OVA) or saline in weeks 7-8.
      Regardless of whether they inhaled OVA or saline, mice were sensitized by OVA
      injections in weeks 11 and 13 followed by OVA aerosol challenge in weeks 14-15.
      At three time points, we assessed OVA-specific serum immunoglobins,
      bronchoalveolar lavage cells and cytokines, lung and nasal histopathology, and
      airway hyperresponsiveness (AHR). RESULTS: At 6 weeks, we found no significant
      differences between in utero ETS and AIR mice. At 10 weeks, following OVA
      aerosol, ETS mice displayed greater AHR than AIR mice (alpha = 0.05),
      unaccompanied by changes in histopathology, cytokine profile, or antibody levels.
      At 15 weeks, mice that had inhaled saline in weeks 7-8 developed airway
      inflammation: eosinophilia (alpha = 0.05), interleukin-5 (alpha = 0.05), and AHR
      (alpha = 0.05) were greater in ETS mice than in AIR mice. Mice that had inhaled
      OVA in weeks 7-8 demonstrated no airway inflammation after sensitization and
      challenge. CONCLUSION: In utero ETS exposure exacerbates subsequent adult
      responses to initial allergen exposure.

PMID- 17450225
TI  - The NIEHS Environmental Health Sciences Data Resource Portal: placing advanced
      technologies in service to vulnerable communities.
AB  - BACKGROUND: Two devastating hurricanes ripped across the Gulf Coast of the United
      States during 2005. The effects of Hurricane Katrina were especially severe: the
      human and environmental health impacts on New Orleans, Louisiana, and other Gulf
      Coast communities will be felt for decades to come. The Federal Emergency
      Management Agency (FEMA) estimates that Katrina's destruction disrupted the lives
      of roughly 650,000 Americans. Over 1,300 people died. The projected economic
      costs for recovery and reconstruction are likely to exceed $125 billion.
      OBJECTIVES: The NIEHS (National Institute of Environmental Health Sciences)
      Portal aims to provide decision makers with the data, information, and the tools
      they need to a) monitor human and environmental health impacts of disasters; b)
      assess and reduce human exposures to contaminants; and c) develop science-based
      remediation, rebuilding, and repopulation strategies. METHODS: The NIEHS Portal
      combines advances in geographic information systems (GIS), data
      mining/integration, and visualization technologies through new forms of grid
      based (distributed, web-accessible) cyberinfrastructure. RESULTS: The scale and
      complexity of the problems presented by Hurricane Katrina made it evident that no
      stakeholder alone could tackle them and that there is a need for greater
      collaboration. The NIEHS Portal provides a collaboration-enabling, information
      laden base necessary to respond to environmental health concerns in the Gulf
      Coast region while advancing integrative multidisciplinary research. CONCLUSIONS:
      The NIEHS Portal is poised to serve as a national resource to track environmental
      hazards following natural and man-made disasters, focus medical and environmental
      response and recovery resources in areas of greatest need, and function as a test
      bed for technologies that will help advance environmental health sciences
      research into the modern scientific and computing era.

PMID- 17450224
TI  - Ontogenetic alterations in molecular and structural correlates of dendritic
      growth after developmental exposure to polychlorinated biphenyls.
AB  - OBJECTIVE: Perinatal exposure to polychlorinated biphenyls (PCBs) is associated
      with decreased IQ scores, impaired learning and memory, psychomotor difficulties,
      and attentional deficits in children. It is postulated that these
      neuropsychological deficits reflect altered patterns of neuronal connectivity. To
      test this hypothesis, we examined the effects of developmental PCB exposure on
      dendritic growth. METHODS: Rat dams were gavaged from gestational day 6 through
      postnatal day (PND) 21 with vehicle (corn oil) or the commercial PCB mixture
      Aroclor 1254 (6 mg/kg/day). Dendritic growth and molecular markers were examined
      in pups during development. RESULTS: Golgi analyses of CA1 hippocampal pyramidal
      neurons and cerebellar Purkinje cells indicated that developmental exposure to
      PCBs caused a pronounced age-related increase in dendritic growth. Thus, even
      though dendritic lengths were significantly attenuated in PCB-treated animals at
      PND22, the rate of growth was accelerated at later ages such that by PND60,
      dendritic growth was comparable to or even exceeded that observed in vehicle
      controls. Quantitative reverse transcriptase polymerase chain reaction analyses
      demonstrated that from PND4 through PND21, PCBs generally increased expression of
      both spinophilin and RC3/neurogranin mRNA in the hippocampus, cerebellum, and
      cortex with the most significant increases observed in the cortex. CONCLUSIONS:
      This study demonstrates that developmental PCB exposure alters the ontogenetic
      profile of dendritogenesis in critical brain regions, supporting the hypothesis
      that disruption of neuronal connectivity contributes to neuropsychological
      deficits seen in exposed children.

PMID- 17450226
TI  - Identification of genes implicated in methapyrilene-induced hepatotoxicity by
      comparing differential gene expression in target and nontarget tissue.
AB  - BACKGROUND: Toxicogenomics experiments often reveal thousands of transcript
      alterations that are related to multiple processes, making it difficult to
      identify key gene changes that are related to the toxicity of interest.
      OBJECTIVES: The objective of this study was to compare gene expression changes in
      a nontarget tissue to the target tissue for toxicity to help identify toxicity
      related genes. METHODS: Male rats were given the hepatotoxicant methapyrilene at
      two dose levels, with livers and kidneys removed 24 hr after one, three, and
      seven doses for gene expression analysis. To identify gene changes likely to be
      related to toxicity, we analyzed genes on the basis of their temporal pattern of
      change using a program developed at the National Institute of Environmental
      Health Sciences, termed "EPIG" (extracting gene expression patterns and
      identifying co-expressed genes). RESULTS: High-dose methapyrilene elicited
      hepatic damage that increased in severity with the number of doses, whereas no
      treatment-related lesions were observed in the kidney. High-dose methapyrilene
      elicited thousands of gene changes in the liver at each time point, whereas many
      fewer gene changes were observed in the kidney. EPIG analysis identified patterns
      of gene expression correlated to the observed toxicity, including genes
      associated with endoplasmic reticulum stress and the unfolded protein response.
      CONCLUSIONS: By factoring in dose level, number of doses, and tissue into the
      analysis of gene expression elicited by methapyrilene, we were able to identify
      genes likely to not be implicated in toxicity, thereby allowing us to focus on a
      subset of genes to identify toxicity-related processes.

PMID- 17450227
TI  - Vermiculite, respiratory disease, and asbestos exposure in Libby, Montana: update
      of a cohort mortality study.
AB  - BACKGROUND: Vermiculite from the mine near Libby, Montana, is contaminated with
      tremolite asbestos and other amphibole fibers (winchite and richterite). Asbestos
      contaminated Libby vermiculite was used in loose-fill attic insulation that
      remains in millions of homes in the United States, Canada, and other countries.
      OBJECTIVE: This report describes asbestos-related occupational respiratory
      disease mortality among workers who mined, milled, and processed the Libby
      vermiculite. METHODS: This historical cohort mortality study uses life table
      analysis methods to compare the age-adjusted mortality experience through 2001 of
      1,672 Libby workers to that of white men in the U.S. population. RESULTS: Libby
      workers were significantly more likely to die from asbestosis [standardized
      mortality ratio (SMR) = 165.8; 95% confidence interval (CI), 103.9-251.1], lung
      cancer (SMR = 1.7; 95% CI, 1.4-2.1), cancer of the pleura (SMR = 23.3; 95% CI,
      6.3-59.5), and mesothelioma. Mortality from asbestosis and lung cancer increased
      with increasing duration and cumulative exposure to airborne tremolite asbestos
      and other amphibole fibers. CONCLUSIONS: The observed dose-related increases in
      asbestosis and lung cancer mortality highlight the need for better understanding
      and control of exposures that may occur when homeowners or construction workers
      (including plumbers, cable installers, electricians, telephone repair personnel,
      and insulators) disturb loose-fill attic insulation made with asbestos
      contaminated vermiculite from Libby, Montana.

PMID- 17450228
TI  - Pulmonary biomarkers based on alterations in protein expression after exposure to
      arsenic.
AB  - OBJECTIVE: Environmental exposure to arsenic results in multiple adverse effects
      in the lung. Our objective was to identify potential pulmonary protein biomarkers
      in the lung-lining fluid of mice chronically exposed to low-dose As and to
      validate these protein changes in human populations exposed to As. METHODS: Mice
      were administered 10 or 50 ppb As (sodium arsenite) in their drinking water for 4
      weeks. Proteins in the lung-lining fluid were identified using two-dimensional
      gel electrophoresis (n = 3) or multidimensional protein identification technology
      (MUDPIT) (n = 2) coupled with mass spectrometry. Lung-induced sputum samples were
      collected from 57 individuals (tap water As ranged from ~ 5 to 20 ppb). Protein
      levels in sputum were determined by ELISA, and As species were analyzed in first
      morning void urine. RESULTS: Proteins in mouse lung-lining fluid whose expression
      was consistently altered by As included glutathione-S-transferase (GST)-omega-1,
      contraspin, apolipoprotein A-I and A-IV, enolase-1, peroxiredoxin-6, and receptor
      for advanced glycation end products (RAGE). Validation of the putative biomarkers
      was carried out by evaluating As-induced alterations in RAGE in humans.
      Regression analysis demonstrated a significant negative correlation (p = 0.016)
      between sputum levels of RAGE and total urinary inorganic As, similar to results
      seen in our animal model. CONCLUSION: Combinations of proteomic analyses of
      animal models followed by specific analysis of human samples provide an unbiased
      determination of important, previously unidentified putative biomarkers that may
      be related to human disease.

PMID- 17450229
TI  - Perinatal bisphenol A exposure increases estrogen sensitivity of the mammary
      gland in diverse mouse strains.
AB  - BACKGROUND: Studies of low-dose effects of xenoestrogens have yielded conflicting
      results that may be attributed to differences in estrogen sensitivity between the
      rodent strains examined. Perinatal exposure of CD-1 mice to low doses of the
      xenoestrogen bisphenol A (BPA) alters peripubertal mammary gland development.
      Future studies to assess the role of estrogen receptors as mediators of BPA
      action require estrogen receptor knock-out mice that were generated on a C57Bl6
      background. The sensitivity of the C57Bl6 strain to estradiol and BPA is unknown.
      OBJECTIVES: In the present study we examined whether the mammary glands of CD-1
      and C57Bl6 mice exhibited similar responses to 17beta-estradiol (E(2)) and
      whether perinatal exposure to BPA equally enhanced sensitivity of the mammary
      glands to E(2) at puberty. METHODS: Immature mice were ovariectomized and treated
      for 10 days with one of eight doses of E(2). Morphological mammary gland
      parameters were examined to identify doses producing half-maximal effects. Mice
      were exposed perinatally to 0 or 250 ng BPA/kg body weight (bw)/day from
      gestational day 8 until postnatal day (PND) 2. On PND25, female offspring were
      ovariectomized and given an estrogen challenge of 0, 0.5, or 1 microg E(2)/kg
      bw/day for 10 days. Morphometric parameters of the mammary gland were compared
      between strains. RESULTS: Both strains exhibited similar responses to E(2).
      Perinatal BPA exposure altered responses to E(2) at puberty for several
      parameters in both strains, although the effect in CD-1 was slightly more
      pronounced. CONCLUSION: Both mouse strains provide adequate models for the study
      of perinatal exposure to xenoestrogens.

PMID- 17450230
TI  - Genetic polymorphisms influencing arsenic metabolism: evidence from Argentina.
AB  - The susceptibility to arsenic-induced diseases differs greatly between
      individuals, possibly due to interindividual variations in As metabolism that
      affect retention and distribution of toxic metabolites. To elucidate the role of
      genetic factors in As metabolism, we studied how polymorphisms in six genes
      affected the urinary metabolite pattern in a group of indigenous women (n = 147)
      in northern Argentina who were exposed to approximately 200 microg/L As in
      drinking water. These women had low urinary percentages of monomethylated As
      (MMA) and high percentages of dimethylated As (DMA). MMA has been associated with
      adverse health effects, and DMA has the lowest body retention of the metabolites.
      The genes studied were arsenic(+III)methyltransferase (AS3MT), glutathione S
      transferase omega 1 (GSTO1), 5-methyltetrahydrofolate-homocysteine
      methyltransferase (MTR), methylenetetrahydrofolate reductase (MTHFR), and
      glutathione S-transferases mu 1 (GSTM1) and theta 1 (GSTT1). We found three
      intronic polymorphisms in AS3MT (G12390C, C14215T, and G35991A) associated with a
      lower percentage of MMA (%MMA) and a higher percentage of DMA (%DMA) in urine.
      The variant homozygotes showed approximately half the %MMA compared with wild
      type homozygotes. These polymorphisms were in strong linkage, with high allelic
      frequencies (72-76%) compared with other populations. We also saw minor effects
      of other polymorphisms in the multivariate regression analysis with effect
      modification for the deletion genotypes for GSTM1 (affecting %MMA) and GSTT1
      (affecting %MMA and %DMA). For pregnant women, effect modification was seen for
      the folate-metabolizing genes MTR and MTHFR. In conclusion, these findings
      indicate that polymorphisms in AS3MT-and possibly GSTM1, GSTT1, MTR, and MTHFR
      are responsible for a large part of the interindividual variation in As
      metabolism and susceptibility.

PMID- 17450231
TI  - Case report: potential arsenic toxicosis secondary to herbal kelp supplement.
AB  - CONTEXT: Medicinal use of dietary herbal supplements can cause inadvertent
      arsenic toxicosis. CASE PRESENTATION: A 54-year-old woman was referred to the
      University of California, Davis, Occupational Medicine Clinic with a 2-year
      history of worsening alopecia and memory loss. She also reported having a rash,
      increasing fatigue, nausea, and vomiting, disabling her to the point where she
      could no longer work full-time. A thorough exposure history revealed that she
      took daily kelp supplements. A urine sample showed an arsenic level of 83.6
      microg/g creatinine (normal < 50 microg/g creatinine). A sample from her kelp
      supplements contained 8.5 mg/kg (ppm) arsenic. Within weeks of discontinuing the
      supplements, her symptoms resolved and arsenic blood and urine levels were
      undetectable. DISCUSSION: To evaluate the extent of arsenic contamination in
      commercially available kelp, we analyzed nine samples randomly obtained from
      local health food stores. Eight of the nine samples showed detectable levels of
      arsenic higher than the Food and Drug Administration tolerance level of 0.5 to 2
      ppm for certain food products. None of the supplements contained information
      regarding the possibility of contamination with arsenic or other heavy metals.
      The 1994 Dietary Supplement Health and Education Act (DSHEA) has changed the way
      dietary herbal therapies are marketed and regulated in the United States. Less
      regulation of dietary herbal therapies will make inadvertent toxicities a more
      frequent occurrence. RELEVANCE TO CLINICAL PRACTICE: Clinicians should be aware
      of the potential for heavy metal toxicity due to chronic use of dietary herbal
      supplements. Inquiring about use of dietary supplements is an important element
      of the medical history.

PMID- 17450232
TI  - Dose-response relationship of prenatal mercury exposure and IQ: an integrative
      analysis of epidemiologic data.
AB  - BACKGROUND: Prenatal exposure to mercury has been associated with adverse
      childhood neurologic outcomes in epidemiologic studies. Dose-response information
      for this relationship is useful for estimating benefits of reduced mercury
      exposure. OBJECTIVES: We estimated a dose-response relationship between maternal
      mercury body burden and subsequent childhood decrements in intelligence quotient
      (IQ), using a Bayesian hierarchical model to integrate data from three
      epidemiologic studies. METHODS: Inputs to the model consist of dose-response
      coefficients from studies conducted in the Faroe Islands, New Zealand, and the
      Seychelles Islands. IQ coefficients were available from previous work for the
      latter two studies, and a coefficient for the Faroe Islands study was estimated
      from three IQ subtests. Other tests of cognition/achievement were included in the
      hierarchical model to obtain more accurate estimates of study-to-study and end
      point-to-end point variability. RESULTS: We find a central estimate of -0.18 IQ
      points (95% confidence interval, -0.378 to -0.009) for each parts per million
      increase of maternal hair mercury, similar to the estimates for both the Faroe
      Islands and Seychelles studies, and lower in magnitude than the estimate for the
      New Zealand study. Sensitivity analyses produce similar results, with the IQ
      coefficient central estimate ranging from -0.13 to -0.25. CONCLUSIONS: IQ is a
      useful end point for estimating neurodevelopmental effects, but may not fully
      represent cognitive deficits associated with mercury exposure, and does not
      represent deficits related to attention and motor skills. Nevertheless, the
      integrated IQ coefficient provides a more robust description of the dose-response
      relationship for prenatal mercury exposure and cognitive functioning than results
      of any single study.

PMID- 17450233
TI  - Parental smoking modifies the relation between genetic variation in tumor
      necrosis factor-alpha (TNF) and childhood asthma.
AB  - BACKGROUND: Polymorphisms in the proinflammatory cytokine genes tumor necrosis
      factor-alpha (TNF) and lymphotoxin-alpha (LTA, also called TNF-beta) have been
      associated with asthma and atopy in some studies. Parental smoking is a
      consistent risk factor for childhood asthma. Secondhand smoke and ozone both
      stimulate TNF production. OBJECTIVES: Our goal was to investigate whether genetic
      variation in TNF and LTA is associated with asthma and atopy and whether the
      association is modified by parental smoking in a Mexican population with high
      ozone exposure. METHODS: We genotyped six tagging single nucleotide polymorphisms
      (SNPs) in TNF and LTA, including functional variants, in 596 nuclear families
      consisting of asthmatics 4-17 years of age and their parents in Mexico City.
      Atopy was determined by skin prick tests. RESULTS: The A allele of the TNF-308
      SNP was associated with increased risk of asthma [relative risk (RR) = 1.54; 95%
      confidence interval (CI), 1.04-2.28], especially among children of non-smoking
      parents (RR = 2.06; 95% CI, 1.19-3.55; p for interaction = 0.09). Similarly, the
      A allele of the TNF-238 SNP was associated with increased asthma risk among
      children of nonsmoking parents (RR = 2.21; 95% CI, 1.14-4.30; p for interaction =
      0.01). LTA SNPs were not associated with asthma. Haplotype analyses reflected the
      single SNP findings in magnitude and direction. TNF and LTA SNPs were not
      associated with the degree of atopy. CONCLUSIONS: Our results suggest that
      genetic variation in TNF may contribute to childhood asthma and that associations
      may be modified by parental smoking.

PMID- 17450235
TI  - Elevated blood lead concentrations and vitamin D deficiency in winter and summer
      in young urban children.
AB  - BACKGROUND: It is widely recognized that blood lead concentrations are higher in
      the summer than in winter. Although the effects of some environmental factors
      such as lead in dust on this phenomenon have been studied, relationships to
      sunlight-induced vitamin D synthesis have not been adequately investigated.
      Vitamin D status is influenced by the diet, sunlight exposure, age, skin
      pigmentation, and other factors, and may modify gastrointestinal lead absorption
      or release of lead stored in bones into the bloodstream. OBJECTIVE AND METHODS:
      We collected paired blood samples from 142 young, urban African-American and
      Hispanic children in the winter and summer to study the seasonal increase in
      blood lead and its relationships to vitamin D nutrition, age, and race. RESULTS:
      A winter/summer (W/S) increase in blood lead concentrations of 32.4% was found
      for children 1-3 years of age. There was a smaller W/S increase of 13.0% in
      children 4-8 years of age. None of the 51 Hispanic children had an elevated blood
      lead concentration (> or = 10 microg/dL) during the winter, and only one had an
      elevated summertime concentration. In contrast, elevated blood lead
      concentrations were frequent in the 91 African-American children, especially
      those 1-3 years of age. For the latter, the percentage with elevated blood lead
      levels increased from 12.2% in winter to 22.5% in summer. A 1.2% W/S increase in
      serum 25-hydroxy-vitamin D (serum 25-OH-D) concentrations was found for children
      1-3 years of age. However, in children 4-8 years of age the W/S increase in serum
      25-OH-D was much larger-33.6%. The percentages of children with low (< 16
      microg/L) serum 25-OH-D concentrations were 12.0% in winter and 0.7% in summer
      and were consistently greater in African-American than in Hispanic children. The
      seasonal increases in blood lead and serum 25-OH-D in children 4-8 years of age
      were significantly associated. CONCLUSION: The higher summertime serum 25-OH-D
      concentrations for the 4- to 8-year-old children are likely caused by increased
      sunlight-induced vitamin D synthesis and may contribute to the seasonal increase
      in blood lead. Age and race are key factors that affect blood lead and vitamin D
      nutrition, as well as their interactions, in young urban children.

PMID- 17450234
TI  - Smoking during pregnancy affects speech-processing ability in newborn infants.
AB  - BACKGROUND: Tobacco smoking during pregnancy is known to adversely affect
      development of the central nervous system in babies of smoking mothers by
      restricting utero-placental blood flow and the amount of oxygen available to the
      fetus. Behavioral data associate maternal smoking with lower verbal scores and
      poorer performance on specific language/auditory tests. OBJECTIVES: In the
      current study we examined the effects of maternal smoking during pregnancy on
      newborns' speech processing ability as measured by event-related potentials
      (ERPs). METHOD: High-density ERPs were recorded within 48 hr of birth in healthy
      newborn infants of smoking (n = 8) and nonsmoking (n = 8) mothers. Participating
      infants were matched on sex, gestational age, birth weight, Apgar scores,
      mother's education, and family income. Smoking during pregnancy was determined by
      parental self-report and medical records. ERPs were recorded in response to six
      consonant-vowel syllables presented in random order with equal probability.
      RESULTS: Brainwaves of babies of nonsmoking mothers were characterized by typical
      hemisphere asymmetries, with larger amplitudes over the left hemisphere,
      especially over temporal regions. Further, infants of nonsmokers discriminated
      among a greater number of syllables whereas the newborns of smokers began the
      discrimination process at least 150 msec later and differentiated among fewer
      stimuli. CONCLUSIONS: Our findings indicate that prenatal exposure to tobacco
      smoke in otherwise healthy babies is linked with significant changes in brain
      physiology associated with basic perceptual skills that could place the infant at
      risk for later developmental problems.

PMID- 17450236
TI  - Health effects of exposure to natural arsenic in groundwater and coal in China:
      an overview of occurrence.
AB  - Between 2001 and 2005, 21,155 of 445,638 wells in 20,517 villages in 292 counties
      in 16 provinces from China, or 5% of wells, were found to contain > 50 microg/L
      arsenic (As) by field testing with the Merck As kit. We achieved quality
      assurance of analysis of at least 10% of the wells containing > 50 microg/L As
      using hydride generation atomic fluorescence spectrometry and silver
      dithiodicarbomate spectrometry. Our best estimate of the population exposed to >
      50 microg/L As in drinking water was 582,769. This is probably an underestimate
      for China because of the limited area surveyed. In a survey of 135,492
      individuals in eight provinces, we used the National Diagnosis Standard for
      Endemic Arsenicosis and identified 10,096 cases of arsenicosis with various
      degrees of skin lesions. The arsenicosis occurrence rate of 7.5% is likely an
      overestimate, because the survey focused more on known and suspected endemic
      areas of arsenicosis. The occurrence of arsenicosis correlates positively with
      the percentage of wells containing > 50 microg/L As, or at a ratio of 1 to 5%.
      Based on both the amount of As in well water and the rate of occurrence of
      arsenicosis, Shanxi province, Inner Mongolia autonomous region, and Jilin
      province are the top three areas in China as of 2005 for exposure to endemic As
      from drinking water. Our survey also identified exposure to high levels of As
      from wells in several provinces and from the indoor burning of coal containing
      high levels of As in Shaanxi province. These areas, however, have not had any
      reports of previous arsenicosis endemics. In the endemic areas, the average rate
      of occurrence of arsenicosis at advanced stages was 1.2%, possibly because of a
      long exposure time of > 20 years; the rate of occurrence increased to 2.7% when
      we included a high dose of As exposure from the indoor burning of coal.
      Mitigation to reduce As exposure remains a challenge in rural China.

PMID- 17450237
TI  - Arsenic and fluoride exposure in drinking water: children's IQ and growth in
      Shanyin county, Shanxi province, China.
AB  - BACKGROUND: Recently, in a cross-sectional study of 201 children in Araihazar,
      Bangladesh, exposure to arsenic (As) in drinking water has been shown to lower
      the scores on tests that measure children's intellectual function before and
      after adjustment for sociodemographic features. OBJECTIVES: We investigated the
      effects of As and fluoride exposure on children's intelligence and growth.
      METHODS: We report the results of a study of 720 children between 8 and 12 years
      of age in rural villages in Shanyin county, Shanxi province, China. The children
      were exposed to As at concentrations of 142 +/- 106 microg/L (medium-As group)
      and 190 +/- 183 microg/L (high-As group) in drinking water compared with the
      control group that was exposed to low concentrations of As (2 +/- 3 microg/L) and
      low concentrations of fluoride (0.5 +/- 0.2 mg/L). A study group of children
      exposed to high concentrations of fluoride (8.3 +/- 1.9 mg/L) but low
      concentrations of As (3 +/- 3 microg/L) was also included because of the common
      occurrence of elevated concentrations of fluoride in groundwater in our study
      area. A standardized IQ (intelligence quotient) test was modified for children in
      rural China and was based on the classic Raven's test used to determine the
      effects of these exposures on children's intelligence. A standardized measurement
      procedure for weight, height, chest circumference, and lung capacity was used to
      determine the effects of these exposures on children's growth. RESULTS: The mean
      IQ scores decreased from 105 +/- 15 for the control group, to 101 +/- 16 for the
      medium-As group (p < 0.05), and to 95 +/- 17 for the high-As group (p < 0.01).
      The mean IQ score for the high-fluoride group was 101 +/- 16 and significantly
      different from that of the control group (p < 0.05). Children in the control
      group were taller than those in the high-fluoride group (p < 0.05); weighed more
      than the those in the high-As group (p < 0.05); and had higher lung capacity than
      those in the medium-As group (p < 0.05). CONCLUSIONS: Children's intelligence and
      growth can be affected by high concentrations of As or fluoride. The IQ scores of
      the children in the high-As group were the lowest among the four groups we
      investigated. It is more significant that high concentrations of As affect
      children's intelligence. It indicates that arsenic exposure can affect children's
      intelligence and growth.

PMID- 17450238
TI  - Urinary arsenic metabolites in children and adults exposed to arsenic in drinking
      water in Inner Mongolia, China.
AB  - BACKGROUND: We report the concentrations and distributions of urinary arsenic
      (As) metabolites in 233 residents exposed to 20, 90, or 160 microg/L inorganic
      arsenic (iAs) in drinking water from three villages in Hohhot, Inner Mongolia,
      China, that formed one control and two exposed groups. METHODS: We used hydride
      generation-atomic absorption spectrometry (HGAAS) to determine iAs,
      monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA). RESULTS: The
      concentrations of each urinary As species in the two exposed groups were
      significantly higher than in the control group for both children and adults. Both
      children and adults in exposed groups had higher percent iAs and MMA and lower
      percent DMA, and low primary and secondary methylation indices (PMI and SMI,
      respectively) than those in the control group. However, children showed
      significant increases in percent DMA and the SMI as well as decreases in the
      percent MMA when the iAs exposure level increased from 90 to 160 microg/L. In
      addition, children in the two exposed groups showed lower percent MMA but higher
      percent DMA and higher SMI than adults in the same exposed group. No significant
      differences in As metabolite concentrations and distributions were found between
      males and females in each group. A significant correlation was also found in the
      SMI between 11 pairs of children and their mothers from the 160-microg/L-exposed
      group. CONCLUSIONS: Children had higher a capacity for secondary methylation of
      As than adults when exposed to the same concentrations of iAs in drinking water.
      Exposure to As may increase the capacity for methylation in children to some
      extent.

PMID- 17450239
TI  - Unventilated indoor coal-fired stoves in Guizhou province, China: cellular and
      genetic damage in villagers exposed to arsenic in food and air.
AB  - BACKGROUND: Inorganic arsenic (iAs) is a well-known human carcinogen recognized
      by the World Health Organization and the International Agency for Research on
      Cancer. Currently, most iAs studies in populations are concerned with drinking
      water and occupational arsenicosis. In Guizhou province, arsenicosis caused by
      the burning of coal in unventilated indoor stoves is an unusual type of exposure.
      Because the poisoning mechanism involved in arsenicosis is as yet unknown and no
      effective therapy exists, progress has been slow on the prevention and therapy of
      arsenicosis. OBJECTIVES: We examined the relationship between arsenic (As)
      exposure from the burning of coal in unventilated indoor stoves and genetic
      damage in humans, using cellular and molecular indices. We selected villagers
      from Jiaole township, Guizhou province, China, who had been exposed to milligram
      levels of As daily via food and air contaminated by the burning of As-containing
      coal in unventilated indoor stoves. RESULTS: The As-exposed subjects from Jiaole
      were divided into four groups according to skin lesion symptoms: nonpatients,
      mild, intermediate, and severe arsenicosis. Another 53 villagers from a town 12
      km from Jiaole were recruited as the external control group. In the four groups
      of exposed subjects, As concentrations in urine and hair were 76-145 microg/L and
      5.4-7.9 microg/g, respectively. These values were higher than those in the
      external control group, which had As concentrations of 46 microg/L for urine and
      1.6 microg/g for hair. We measured sister chromatid exchange and chromosomal
      aberrations to determine human chromosome damage, and for DNA damage, we measured
      DNA single-strand breaks and DNA-protein cross-links. All measurements were
      higher in the four exposed groups compared with the external control group. DNA
      repair was impaired by As exposure, as indicated by the mRNA of O-6-methylguanine
      DNA methyltransferase (MGMT), X-ray repair complementing defective repair in
      Chinese hamster cells 1 (XRCC1), and, to a lesser extent, by the mismatch repair
      gene hMSH2 mRNA. The expression of mutant-type p53 increased with aggravation of
      arsenicosis symptoms, whereas the expression of p16-INK4(p16) decreased. p53
      mutated at a frequency of 30-17% in the carcinoma (n = 10) and precarcinoma (n =
      12) groups. No mutation was found in p16, although deletion was evident. Deletion
      rates were 8.7% (n = 23) and 38.9% (n = 18) in noncarcinoma and carcinoma groups,
      respectively. CONCLUSIONS: The results showed that long-term As exposure may be
      associated with damage of chromosomes and DNA, gene mutations, gene deletions,
      and alterations of DNA synthesis and repair ability.

PMID- 17450240
TI  - Unventilated indoor coal-fired stoves in Guizhou province, China: reduction of
      arsenic exposure through behavior changes resulting from mitigation and health
      education in populations with arsenicosis.
AB  - We report the results of a coordinated mitigation effort aimed at reducing
      arsenic (As) exposure in three counties of Guizhou province, China. Mitigation
      occurred in 2005 and encompassed 21 villages with 47,000 inhabitants, who were
      exposed to high levels of As in their diet through consumption of As-contaminated
      chili peppers and corn dried over unventilated stoves that burned coal containing
      high levels of As. The coal was mined by villagers from local pits. Inhalation of
      air that contained high levels of As contributed to approximately 25% of the
      daily As intake of 6-9 mg. Before mitigation, a baseline survey of 45,364
      residents in 2004 identified more than 2,800 individuals with arsenicosis. The
      survey also found that many residents were aware of the health effects of As in
      general but lacked in-depth understanding of the link between coal use and
      arsenicosis. Consequently, an overwhelming majority (> 95%) continued to use high
      As coal. This survey provided the basis for a health education campaign that
      promoted lifestyle changes coupled with the shutting down of local coal pits and
      the installation of 10,000 new stoves with chimneys for ventilation. The cost of
      the mitigation was about 4 million Yuan RMB (US$500,000) and was financed mostly
      by the government. A postmitigation response survey in 2005 found that > 85% of
      the residents now associate the use of coal with arsenicosis; > 90% correctly
      learned to operate the new ventilated stoves; and > 90% dry corn and chili
      peppers outdoors in the sun. Urinary As concentrations in the region decreased
      from 0.198 +/- 0.300 mg/L (n = 144) in 2004 to 0.049 +/- 0.009 mg/L (n = 50) in
      2005 in individuals with arsenicosis (p < 0.01), which is consistent with the
      behavior changes.

PMID- 17450241
TI  - The sodium-iodine symporter and the proton-pump inhibitors in - related to the
      side effects of- the treatment of thyroid cancer with iodine-131.
AB  - Iodine-131 ((131)I) administered to patients for imaging or treatment,
      concentrates in the gastrointestinal tract, including the salivary glands,
      stomach and bowel. In Nuclear Medicine practice this biological property of
      iodine causes side effects when the therapeutic dose of (131)I is large. This
      occurs during the treatment of patients with differentiated thyroid carcinoma
      (DTC). During this clinical application, the dose of (131)I is higher than 3.7
      GBq. Side effects of this treatment with respect to the stomach, include
      gastritis as an inflammatory reaction to radiation, anorexia due to gastric
      atrophy and rarely megaloblastic anemia due to lack of the endogenous factor.
      Side effects can also include xerostomia. We have recently tried to prevent
      gastric side effects by prescribing proton pump inhibitors (PPI) for patients
      with DTC prior to treatment with (131)I. PPI block the excretion of hydrochloric
      acid from the gastric mucosa and are utilized for the prevention and treatment of
      gastritis, gastric ulcers and gastroesophageal reflux. Whole body scans before or
      after the administration of PPI, showed that PPI do not interfere with the
      biologic distribution of (131)I. These findings were not surprising. Recent
      studies in animals and humans have shown that the accumulation and concentration
      of iodine by the thyroid gland is the result of the selective action of sodium
      iodine symporter (Na+I+symporter, NIS). Furthermore, it was shown that the
      accumulation and concentration of (131)I in the parietal cells of the gastric
      mucosa, the ductal cells of the salivary glands and the alveolar epithelial cells
      of the mammary glands, is analogous to the biologic action of NIS in the thyroid
      cells. The gastric mucosa accumulates iodine from the capillaries via the
      extracellular/extravascular space and finally excretes it into the lumen of the
      stomach, from where it is passively transferred into the bowel, where it is
      partially reabsorbed to once again enter its metabolic cycle. On the contrary, as
      it is now known, the PPI have an entirely different metabolic action, which is
      unrelated to that of the NIS, although both mechanisms coexist in the parietal
      cells of the gastric mucosa. Thus, during the application of (131)I for imaging
      or for the treatment of DTC patients, except for the short period of time
      immediately after the oral administration, when the radionuclide passes through
      the stomach, the concentration of (131)I in the gastrointestinal tract is due to
      its active accumulation and excretion by the gastric mucosa. PPI act only on the
      hydrochloric acid secretion not affecting the biologic properties of iodine.

PMID- 17450242
TI  - Hashimoto's thyroiditis and the role of selenium. Current concepts.
AB  - Hashimoto's thyroiditis (HT) is part of the spectrum of autoimmune thyroid
      diseases. Clinical manifestations of HT are variable and commonly include diffuse
      or nodular goiter with euthyroidism, subclinical hypothyroidism and permanent
      hypothyroidism. Uncommonly, HT causes acute destruction of thyroid tissue and
      release of stored thyroid hormones, causing transient thyrotoxicosis
      (hashitoxicosis). The contribution of methods and techniques of nuclear medicine
      to diagnosis and differential diagnosis of HT is indisputable. In HT patients
      with overt hypothyroidism L-thyroxine (L-T(4)) should be given in the usual
      replacement doses, but in HT patients with a large goiter and normal or elevated
      serum thyroid-stimulating hormone (TSH), L-T(4) may be given in doses sufficient
      to suppress serum TSH. Symptomatic patients with hashitoxicosis and low 24-hour
      thyroid radioactive iodine ((123)I or (123)I) uptake (RIU) may be treated with
      beta-blockers (as propranolol) and sodium ipodate or iopanoic acid (iodinated
      contrast agents) that block the peripheral conversion of T(4) to T(3). Recent
      clinical studies have documented the suppressive effect of selenium treatment on
      serum anti-thyroid peroxidase concentrations in patients with HT.

PMID- 17450243
TI  - Morphology and release kinetics of technetium-99m(V) dimercaptosuccinic acid
      loaded, poly(lactic-co-glycolic)acid microspheric delivery system. An
      experimental approach that may be used for targeted radiation treatment.
AB  - The aim of our studies was to formulate a system that delivers the required
      radiation dose to the tumor site and minimize the harm to other organs or
      tissues. The poly (lactic-co-glycolic acid, 75:25; 50:50) microspheric radiation
      delivery system was fabricated using double emulsion solvent evaporation
      technique for the encapsulation of technetium-99m(V)dimercaptosuccinic acid
      ((99m)Tc(V)DMSA). Microspheres of different sizes (0.2-20.0 mum) were prepared.
      The initial burst in microspheres with 10% and 1% poly vinyl alcohol (PVA) in the
      presence of poly ethylene glucol (PEG) was as 30% and 16% respectively, however
      the initial burst in microspheres without the PEG was 9% and 1.2% respectively.
      The results indicated that smaller microspheres had higher encapsulation (68%) of
      (99m)Tc(V)DMSA than larger microspheres (15%). The stirring rate changed the
      surface of the microspheres from smooth spherical, to spherical, porous. The
      ratio of co-polymers (75:25/50:50) affected the release kinetics. In conclusion,
      our studies with varied surfactant concentrations, co-polymer concentrations and
      speed of solvent evaporation, on the morphology and release kinetics of
      (99m)Tc(V)DMSA from the microspheres, may be applied for the fabrication of
      targeted radiotherapeutic microspheres by substituting (99m)Tc(V)DMSA with
      rhenium-188 (V) DMSA ((188)Re(V)DMSA). (188)Re(V)DMSA is a therapeutic analogue
      of (99m)Tc(V)DMSA and both share similar radiopharmaceutical properties.

PMID- 17450244
TI  - Prescintigraphic morphine application for abdominal adenocarcinoma imaging, with
      technetium-99m methoxy isobutyl isonitrile.
AB  - Imaging of tumors with cationic tracers, especially with technetium-99 methoxy
      isobutyl isonitrile ((99m)Tc-MIBI), revealed high specificity for the diagnosis
      and follow up of various malignancies. However, these radiopharmaceuticals are of
      limited value for the diagnosis of malignancies of the abdominal region due to
      the immediate biliary secretion of the tracer and the associated high background
      activity. In a prospective, single-blinded protocol, patients with endoscopically
      diagnosed gastrointestinal malignancies were assigned to undergo (99m)Tc-MIBI
      imaging of the abdomen. To overcome biliary secretion of cationic tracer we
      administered 0.04 mg/kg morphine hydrochloride intravenously before the
      administration of 600 MBq (99m)Tc-MIBI. Planar images were performed in the
      anterior and posterior views with a double-headed gamma camera and with 3 min
      acquisition time, followed by single photon emission tomography images (3
      degrees, 20 sec/frame). Results were compared to findings of endoscopy, computed
      tomography scan and surgery. Twenty four patients 17 male and 7 female , mean age
      69 years, range 52-83, years were enrolled. All patients suffered from
      adenocarcinoma, (19 from colorectum, 3 from gastric, 1 from pancreatic and one
      patient had both gastric and colorectal adenocarcinoma, for a total of 25 tumor
      lesions). The primary objective- inhibition of biliary secretion- was achieved in
      23 of the 24 patients. (99m)Tc-MIBI-imaging was accumulated intra-abdominally in
      19 patients. In 2 patients the tumor was endoscopically completely removed before
      the scan. In these two patients (99m)Tc-MIBI imaging showed no intra-abdominal
      tracer accumulation. When compared to the endoscopic findings, (99m)Tc-MIBI
      imaging showed time positive results in 13 of the 23 remaining individual tumor
      lesions, false positive in 6 and false negative in 4. This study showed a
      sensitivity of 57% and a specificity of 20% of the above technique for the
      identification of intra-abnominal adenocarcinomas. Correct diagnosis did not
      correlate with tumor size. In conclusion, prescintigraphic morphine
      administration inhibits background activity coming from biliary secretion, and
      enables better intra-abdominal (99m)Tc-MIBI imaging but with limited sensitivity
      and poor specificity.

PMID- 17450245
TI  - Comparison of two software in gated myocardial perfusion single photon emission
      tomography, for the measurement of left ventricular volumes and ejection
      fraction, in patients with and without perfusion defects.
AB  - Emory cardiac toolbox (ECTb) and quantitative gated single photon emission
      tomography - SPET (QGS) software are the two most often used techniques for
      automatic calculation of left ventricular volumes (LVV) and ejection fraction
      (LVEF). Few studies have shown that these software are not interchangeable,
      however the effect of perfusion defects on performance of these software has not
      been widely studied. The aim of this study was to compare the performance of QGS
      and ECTb for the calculation of LVEF, end-systolic volume (ESV) and end-diastolic
      volume (EDV) in patients with normal and abnormal myocardial perfusion. One
      hundred and forty-four consecutive patients with suspected coronary artery
      disease underwent a two-day protocol with dipyridamole stress/rest gated
      technetium-99m-methoxy isobutyl isonitrile ((99m)Tc-sestamibi) myocardial
      perfusion (GSPET) (8 gates/cardiac cycles). Rest GSPET scintiscan findings were
      analyzed using QGS and ECTb. Correlation between the results of QGS and ECTb was
      greater than 90%. In patients with no perfusion defects, EDV and LVEF using ECTb,
      were significantly higher than using QGS (P<0.001), whereas no significant
      difference was noticed in ESV (P=0.741). In patients with perfusion defects, also
      ECTb yielded significantly higher values for EDV, ESV and LVEF than QGS
      (P<0.001). In tomograms of patients with perfusion defects, mean differences of
      EDV and ESV between the two software, were significantly higher than in tomograms
      of patients without defects (P<0.001), while for LVEF this difference was not
      significant (P= 0.093). Patients were classified into three subgroups based on
      the summed rest score (SRS); G1: patients with SRS < or = 3 (n=109), G2: patients
      with 4 < or = SRS < or = 8 (n=13) and G3: patients with SRS > or = 9 (n=22). One
      way ANOVA showed that the mean differences of EDV and ESV values between ECTb and
      QGS between the subgroups were significant (P<0.001 for both parameters), while
      no significant difference was noticed between the subgroups, as for the mean
      difference of LVEF, calculated by the two software (P=0.07). By increasing SRS,
      the EDV and ESV values were overestimated to a higher level by the ECTb as
      compared to the QGS software. Linear regression analysis showed that the
      difference in LVV values, between the two software increased, when SRS also
      increased (P<0.001). In conclusion, correlation between QGS and ECTb, software
      was very good both in patients with and without perfusion defects. In patients
      with perfusion defects, calculated LVEF, ESV and EDV values are higher using ECTb
      compared to the QGS software. However, the more extensive the perfusion defect
      was, the greater the difference of LVV between these two software. For the follow
      up of patients, we suggest the use of a single software either QGS or ECTb, for
      serial measurements of LV function.

PMID- 17450246
TI  - Trapping of technetium-99m albumin macroaggregate and other four
      radiopharmaceuticals by blood clots in vitro.
AB  - Radiopharmaceuticals are known to interact with the blood components (i.e. the
      red blood cells, serum proteins etc) but so far, there have been no data
      regarding their purely mechanical trapping in thrombi. The experiments presented
      in this communication provide evidence that the technetium-99m labeled albumin
      macroaggregate ((99m)Tc-MAA), apparently due to its particle size, can be almost
      quantitatively retained in the in vitro model described. These results can be
      extrapolated in vivo and offer a plausible explanation for either the "hot spot"
      artifact, occasionally seen in lung perfusion imaging or for the partial trapping
      of (99m)Tc-MAA by a thrombus at the tip of a subclavian catheter, as has been
      recently reported. Control experiments were also run using (99m)Tc-methylene
      diphosphonate ((99m)Tc-MDP), (99m)Tc(III)-dimercaptosuccinic acid ((99m)Tc(III)
      DMSA), (99m)Tc-methoxyisobutyl isonitrile ((99m)Tc-MIBI) and sodium pertechnetate
      (Na(99m)TcO(4)), in order to study the extent of trapping of these
      radiopharmaceuticals under identical incubation conditions. (99m)Tc-MDP and
      (99m)Tc(III)-DMSA exhibited the lowest blood clot uptake (partially non-specific
      and partially mechanical trapping), while in the case of (99m)Tc-MIBI and
      Na(99m)TcO(4), besides mechanical and non-specific clot-trapping, transport and
      retention inside the red blood cells was also observed.

PMID- 17450247
TI  - A case of non-malignant multifocal lesions on the methyl diphosphonate technetium
      99m bone scan with enteropathy. SAPHO syndrome.
AB  - This is a case of a 24-year-old man with non-malignant multifocal bone lesions on
      the methyl diphosphonate technetium-99m bone scan, that may represent a variant
      of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. The
      patient complained for diffuse osseous pain, focused mainly in the hip joints. X
      rays of the hips were normal but X-rays of the shoulders showed hyperostosis of
      the right clavicle with no erosions. SAPHO is a rare syndrome of unknown
      aetiology with no more than a hundred cases reported during the last 10 years.
      Its typical form consists of characteristic painful osteoarticular manifestations
      and dermatological findings. In a variant of this syndrome, such as in our case,
      dermatological manifestations may be absent, but hyperostosis with osseous
      hypertrophy and enteropathy are present. No other malignant or benign disease was
      diagnosed. All routine laboratory tests for an inflammatory rheumatoid disease
      were negative. Treatment with non steroid anti-inflammatory agents was successful
      and after six months, there were no clinical symptoms and lesions on the bone
      scan faded. Four years later the patient remained free from symptoms. We discuss
      the scintigraphic, radiological laboratory clinical findings, the therapeutic
      criterion and the exclusion of any malignant or other benign bone disease that
      suggest the diagnosis of SAPHO syndrome. In conclusion, although we were unable
      to perform a bone biopsy, we suggest that no other diagnosis but an enteropathic
      variant of SAPHO syndrome may better describe the above clinical and laboratory
      findings. Bone scan findings have a principal diagnostic role in SAPHO syndrome.

PMID- 17450248
TI  - The contribution of conventional nuclear molecular imaging in characterising the
      nature of a growing solitary pulmonary nodule. Report of a case.
AB  - The solitary pulmonary nodule (SPN) is a relatively common imaging finding, often
      representing a diagnostic challenge. Radiological appearance, growth rate
      calculation during follow up and probability of malignancy assessment by the
      Bayes' theorem are widely used for identifying the nature of a SPN. Molecular
      imaging by fluoro-18 deoxy glucose positron emission tomography has
      revolutionised non-invasive diagnosis of lung cancer, but the low-cost, widely
      available conventional nuclear imaging modalities still remain valid in the
      field. We present a case of a growing SPN in a middle-aged male smoker. Growth
      rate assessment by sequential computed tomography scans, over a follow up period
      of five years, was suggestive of benign histology, while Bayesian analysis
      warranted histological confirmation of the nodule's nature. Imaging by both
      labelled somatostatin analogue technetium 99m-depreotide ((99m)Tc-depreotide) and
      thallium 201-chloride was almost exclusive of malignancy. The nodule was excised
      and histology showed a pulmonary hamartoma. We briefly discuss the relative role
      of invasive and non-invasive methods, with emphasis in conventional radionuclide
      molecular imaging, for the identification of the nature of SPN.

PMID- 17450249
TI  - Parallel hole versus pinhole collimator for technetium-99m sestamibi
      scintigraphy, in the diagnosis of parathyromatosis.

PMID- 17450251
TI  - Recommended dietary selenium intakes and selenium concentrations in nuts.

PMID- 17450253
TI  - Zinc as antiperoxidative agent following iodine-131 induced changes on the
      antioxidant system and the morphology of red blood cells.

PMID- 17450254
TI  - [The importance of recombinant human thyroid stimulating hormone in the follow-up
      and treatment of disseminated thyroid cancer after thyroidectomy].
AB  - In patients operated for differentiated thyroid cancer (DTC), before thyroid
      remnant ablation and treatment of metastatic disease, thyroid hormones are
      withdrawn four to six weeks in order to induce an increase in serum thyroid
      stimulating hormone (TSH) of more than 25-30 microU/mL and thus to stimulate
      thyroid gland uptake and retention of iodine-131 ((131)I), given therapeutically.
      Secretion of thyroglobulin (Taug) is also increased. However, thyroid hormone
      withdrawal frequently causes clinical hypothyroidism. Recombinant human TSH
      (rhTSH) can provide TSH stimulation without withdrawal of thyroid hormones. The
      primary clinical utility of rhTSH has been for the post-surgical monitoring in
      patients with DTC but is currently an aid in thyroid remnant ablation and
      treatment of thyroid tumors with encouraging results. In this review we have
      briefly described the findings reported during the period 1994-2006 concerning
      the diagnostic and therapeutic usefulness of rhTSH in patients with DTC after
      total or near total thyroidectomy.

PMID- 17450255
TI  - [Fetus radiation doses from nuclear medicine and radiology diagnostic procedures.
      Potential risks and radiation protection instructions].
AB  - Although in pregnancy it is strongly recommended to avoid diagnostic nuclear
      medicine and radiology procedures, in cases of clinical necessity or when
      pregnancy is not known to the physician, these diagnostic procedures are to be
      applied. In such cases, counseling based on accurate information and
      comprehensive discussion about the risks of radiation exposure to the fetus
      should follow. In this article, estimations of the absorbed radiation doses due
      to nuclear medicine and radiology diagnostic procedures during the pregnancy and
      their possible risk effects to the fetus are examined and then discussed.
      Stochastic and detrimental effects are evaluated with respect to other risk
      factors and related to the fetus absorbed radiation dose and to the post
      conception age. The possible termination of a pregnancy, due to radiation
      exposure is discussed. Special radiation protection instructions are given for
      radiation exposures in cases of possible, confirmed or unknown pregnancies. It is
      concluded that nuclear medicine and radiology diagnostic procedures, if not
      repeated during the pregnancy, are rarely an indication for the termination of
      pregnancy, because the dose received by the fetus is expected to be less than 100
      mSv, which indicates the threshold dose for having deterministic effects.
      Therefore, the risk for the fetus due to these diagnostic procedures is low.
      However, stochastic effects are still possible but will be minimized if the
      radiation absorbed dose to the fetus is kept as low as possible.

PMID- 17450256
TI  - [Serum testosterone, dihydrotestosterone, luteinizing hormone and follicle
      stimulating hormone versus prostate specific antigen in patients with localized
      prostate adenocarcinoma who underwent radical prostatectomy. Radioimmunoassays
      measurements].
AB  - The relation of steroid hormones (SH) with carcinogenesis is not well understood.
      There is a variation of opinions among researchers about the prognostic value of
      serum SH in patients with localized prostate cancer (PC). The aim of this was to
      study serum SH in patients with localized PC before and after radical
      prostatectomy (RP). Seventy patients with mean age 67+/-8 years, were studied.
      The diagnosis was confirmed by histology after a biopsy. None of the patients was
      submitted to hormonal treatment or radiotherapy prior to RP. Serum testosterone
      (TST), dihydrotestosterone (DHT), luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) levels were examined prior RP and one year following
      RP, by radioimmuno assay (RIA) or immunoradiometric assay (IRMA) methods. Based
      on serum PSA levels before and one year after RP, 66 of the patients did not have
      biochemical recurrence while 4 patients developed biochemical recurrence due to
      residual disease and were treated with flutamide and a LH-RH analogue. In the
      group of 66 patients there was a statistically significant increase in serum TST
      (P<0.001), LH (P=0.004) and FSH (P<0.001), and statistically significant decrease
      in serum DHT (P<0.001). In the four patients with biochemical recurrence, TST
      increased and serum DHT, LH and FSH decreased. In this group the reduction of DHT
      and LH, FSH were due to treatment with flutamide and a LH-RH analogue
      respectively. Our findings suggest that after RP increase of serum LH and FSH may
      have caused an increase in serum TSH and a decrease of serum DHT. If those
      changes are due to the hypothalamic-pituitary axis it may be that the prostate
      neoplasm before RP may have secreted a substance that induced a negative feedback
      to the pituitary gonadotrophin secretion, which was unrelated to varying serum
      PSA levels.

PMID- 17450258
TI  - Twenty-five facts about kidney disease in Singapore: in remembrance of World
      Kidney Day.

PMID- 17450257
TI  - [The importance of the tumor marker CYFRA 21-1 in patients with lung cancer after
      surgery or chemotherapy].
AB  - Lung cancer is the most common cancer worldwide with 900,000 new cases each year
      in men and 330,000 in women, being also the major cause of death from cancer. In
      Greece about 4,000 persons die every year due to lung carcinoma. One of the major
      problems in the follow up of these patients is the difficulty of early detection
      of recurrent disease. Tumor markers are of particular interest in this respect.
      Cytokeratines, especially fragment 19, are specified epithelial tissue-proteins
      that show increased levels in patients with carcinomas. CYFRA 21-1 assays
      determine the serum cytokeratin 19 fragment. The aim of our study was to evaluate
      the importance of serum CYFRA 21-1 studied by immunoradiometric assay in patients
      with various types of lung cancer after surgery or chemotherapy. Ninety-six
      consecutive patients were studied during a two years period. Forty-five of them
      had small cell lung cancer (SCLC) and 51 had non-small cell lung cancer (NSCLC).
      Moreover, 52 healthy individuals were studied to estimate the cut off value of
      CYFRA 21-1. Increased serum levels of the marker were found in patients with lung
      cancer compared to controls (P<0.001). The cut off value was estimated as 3.3
      ng/ml with 96% specificity. Before the treatment there was no difference in the
      sensitivity of CYFRA 21-1 for patients with SCLC (21/45 patients had increased
      CYFRA 21-1 levels, 47%) and for patients with NSCLC (27/51 had increased levels,
      52%). Also, before treatment there was a higher sensitivity in NSCLC than in SCLC
      and especially in SCC among other histotypes of NSCLC when different stages of
      the disease were compared. Patients with extended disease, metastatic or
      recurrent disease had also more increased levels of the marker (P<0.001). One
      month after surgical ablation of the primary lung lesion, 28/58 patients showed a
      drop in the levels of the marker as an indication of the tumor ablation. From the
      58 operated patients 35 relapsed and 31/35 showed an increase in CYFRA-21-1
      levels with a sensitivity of 92% and specificity of 95%. From the 38 patients
      that underwent chemotherapy treatment, 24 had a depravation of the disease and
      21/24 had a great increase of serum CYFRA 21-1 with a sensitivity of 89% and
      specificity of 94%. In conclusion, CYFRA 21-1 is a useful tumor marker before and
      after surgical treatment in lung cancer.

PMID- 17450259
TI  - Chronic kidney disease: the ABC of nephrology.

PMID- 17450260
TI  - Demographic and clinical features of 150 pathological gamblers referred to a
      community addictions programme.
AB  - INTRODUCTION: Pathological gambling has been defined as a persistent and
      recurrent maladaptive gambling behaviour that disrupts personal, family and work
      life. The present study reports on the sociodemographic features, gambling
      activity, comorbidity and legal problems in a sample of 150 pathological gamblers
      who sought treatment from the Community Addiction Management Programme (CAMP),
      Singapore over a 4-year period from 2002 to 2006. MATERIALS AND METHODS: Data
      were collected on 150 consecutive subjects who sought treatment at CAMP. Patients
      were administered a semi-structured interview to elicit demographic data, age of
      onset, family history, onset games and types of games ever played, largest debt
      incurred due to gambling, triggers, illegal activities and suicidal attempts by
      their counsellor. Patients were then assessed by the clinicians to establish the
      primary and comorbid diagnoses. RESULTS: The mean age of the subjects was 42.5
      [standard deviation (SD) 10.2] years. The majority of them were males (87.3%) and
      of Chinese origin (97.3%). The most common comorbid disorders were mood disorders
      (n = 22, 14.7%), substance abuse (n = 11, 7.3%) and alcohol abuse or dependence
      (n = 7, 4.7%). Sixteen (10.7%) subjects had a history of suicidal attempts which
      had been precipitated by gambling-related issues. CONCLUSIONS: Pathological
      gambling in our subjects appears to be associated with significant comorbidity
      and financial problems. These are the preliminary findings and further research
      is needed regarding the phenomenology, profile, course and response to treatment
      of pathological gambling disorders.

PMID- 17450261
TI  - Violence-related behaviours among Malaysian adolescents: a cross sectional survey
      among secondary school students in Negeri Sembilan.
AB  - INTRODUCTION: The aim of this study was to determine the prevalence of violence
      related behaviours among adolescents and the factors associated with it. MATERIAL
      AND METHODS: This was a cross-sectional school survey conducted on 4500
      adolescent students, using a structured questionnaire. Data were collected using
      the supervised self-administered questionnaire [a modified version of the Youth
      Risk Behavior Surveillance in the Malaysian National Language (Bahasa Malaysia)].
      RESULTS: Our study showed that 27.9% of students had been involved in a physical
      fight, 6.6% had been injured in a fight, 5.9% had carried a weapon, 7.2% had felt
      unsafe, 18.5% had had their money stolen and 55.0% had had their property stolen.
      Adolescents who carried weapons to school, smoked, used drugs, felt sad or
      hopeless and played truant were more likely to be involved in physical fights
      after adjusting for age, sex, and ethnicity. CONCLUSION: Violence-related
      behaviours among adolescents, especially involvement in physical fights, are
      common and are positively associated with certain factors such as smoking, taking
      drugs, playing truant, feeling sad or hopeless. Interventions designed at
      targeting adolescent violence should also address these factors and target the
      high-risk groups. There may be a need to identify and provide services for
      adolescents who exhibit these factors.

PMID- 17450262
TI  - Diabetes and associated cardiovascular risk factors in Iran: the Isfahan Healthy
      Heart Programme.
AB  - INTRODUCTION: Diabetes mellitus (DM) is one of the major health problems
      worldwide. The aim of this study was to detect the prevalence of DM and its
      associated risk factors in Iran. MATERIALS AND METHODS: This cross-sectional
      study was performed in 3 cities in the central part of Iran on participants over
      the age of 19 years. Sampling was conducted by multi-stage randomised cluster
      method. Initially, a questionnaire consisting of demographic information, drug
      intake and smoking status was filled out. Later, a physical examination was
      performed, including the measurement of systolic blood pressure (SBP) and
      diastolic blood pressure (DBP), body mass index (BMI) and waist-to-hip ratio
      (WHR). Fasting blood sample was drawn and analysed for sugar, total cholesterol
      (TC), triglyceride (TG) and 2-hour postprandial glucose. A fasting blood sugar
      (FBS) of >126 mg/dL or a 2-hour plasma glucose of over 200 mg/dL was considered
      an indication of diabetes. The impaired glucose tolerance test (IGTT) was defined
      with 2-hour plasma glucose of 140 to 200 mg/dL and FBS <126 mg/dL. The collected
      data were analysed with Student's t-test, chi-square test and multiple logistic
      regression analysis. RESULTS: This study was performed on 12,514 subjects (48.9%
      males and 51.1% females). The total prevalence of DM was 6.7% and 5.3% in urban
      and rural areas and 5.4% and 7.1% in males and females, respectively. The mean
      blood glucose rose with age in both sexes, and blood glucose was higher in
      females and in urban areas. IGTT, known and new DM heightens as age increased and
      more than half of the diabetes cases in all age groups were newly diagnosed. The
      mean blood pressure, age, BMI, waist circumference and serum lipids were higher
      in people with DM and IGTT especially in females. Obesity, a family history of
      DM, high blood pressure, high WHR and ageing were associated with a higher
      probability of DM, but sex had no effect on this probability. DISCUSSION AND
      CONCLUSION: Considering the high prevalence of DM in the central regions of Iran,
      providing vast educational programme to prevent this disease is essential and
      screening FBS tests, especially for obese subjects and those with a family
      history of DM, should be taken into account.

PMID- 17450263
TI  - Survival of small-cell lung cancer and its determinants of outcome in Singapore.
AB  - INTRODUCTION: The survival and epidemiology of small-cell lung cancer (SCLC) in
      Singapore has not been described. We aim to present the characteristics as well
      as determine the survival outcome and important prognostic factors for SCLC
      patients. MATERIALS AND METHODS: A retrospective analysis of SCLC patients
      diagnosed from 1999 to 2002 was conducted at the Outram campus, Singapore.
      Clinical characteristics and treatment data were obtained from case records and
      survival data were checked with the registry of births and deaths on 30 May 2005.
      RESULTS: One hundred and eleven patients were analysed. There were 38 (34.2%)
      limited-disease (LD) patients and 73 (65.8%) extensive-disease (ED) patients. The
      majority were current or former smokers (94.7% among LD and 94.5% among ED). More
      patients with LD had good performance status (92% versus 63%, P = 0.0003) and
      were treated with combined chemotherapy and radiotherapy (82% versus 48%, P =
      0.012). The median survival time of LD patients treated with curative
      chemoradiotherapy was 14.2 months (95% CI, 10.96 to 17.44). Those given
      prophylactic cranial irradiation had a median survival time of 16.9 months (95%
      CI, 11.83 to 21.97). For ED patients, the median survival time was 8.17 months
      (95%CI, 5.44 to 10.89). None of the factors analysed were significant prognostic
      factors for LD patients while performance status and type of treatment given were
      significant among ED patients. CONCLUSIONS: We found that the characteristics and
      survival of SCLC patients in Singapore are fairly similar to that of other
      countries.

PMID- 17450264
TI  - Squamous cell carcinoma and Bowen's disease of the skin in Singapore.
AB  - INTRODUCTION: Non-melanoma skin cancer is one of the commonest cancers in
      Singapore and worldwide. The aim of our study was to evaluate the demographic and
      clinicopathological patterns of squamous cell carcinoma (SCC) and Bowen's disease
      (BD) of the skin, in order to better understand the characteristics of these
      tumours in our population. MATERIALS AND METHODS: Histologically proven cases of
      SCC and BD seen at our centre between 2002 and 2003 were retrospectively analysed
      according to age, sex, race, predisposing factors such as immunosuppression and
      ultraviolet therapy, site and size of tumour, histological differentiation and
      subtype, and treatment method. RESULTS: A total of 161 patients were studied--81
      with SCC, 68 with BD, and 12 with both tumours. There were 199 tumours in total-
      105 SCC and 94 BD. For both SCC and BD, males outnumbered females (ratio of 2.4:1
      and 1.5:1 respectively); patient age averaged 72.9 years and 66.8 years
      respectively; and Chinese were the majority race. The mean duration to
      presentation was 21.2 months for SCC compared with 39.9 months for BD, and common
      symptoms were itch, pain and bleeding for both. The mean tumour size was 19.0 mm
      and 18.5 mm, and the commonest site was the head and neck for both. CONCLUSIONS:
      SCC and BD show rather similar patient characteristics, with a predominance among
      males, having a predilection for the head and neck region, and with a tendency
      towards slow growth. As incidences increase worldwide, it is important for
      healthcare providers to be adept at recognising and managing nonmelanoma skin
      cancers.

PMID- 17450265
TI  - Evaluating the optic nerve and retinal nerve fibre layer: the roles of Heidelberg
      retina tomography, scanning laser polarimetry and optical coherence tomography.
AB  - INTRODUCTION: For many years, ophthalmologists have looked at the optic nerve
      head to evaluate the status of glaucoma. Clinical examination of the optic nerve
      head and retinal nerve fibre layer (RNFL) is however, subjective and sometimes
      variable. Recent developments in computer-based imaging technologies have
      provided a means of obtaining quantitative measurements of the optic nerve head
      topography and peripapillary retinal nerve fibre layer thickness. METHODS:
      Multiple searches using Medline were carried out. Additional searches were made
      using reference lists of published papers and book chapters. RESULTS: Studies
      involving three imaging technologies namely, confocal scanning laser
      ophthalmoscopy, scanning laser polarimetry and optical coherence tomography were
      reviewed. Overall, these technologies were reproducible and demonstrate good
      sensitivity and specificity in the range of 70 to 80%. Inclusion of age and
      ethnicity normative database will make these technologies more effective in
      screening and diagnosis. Quantitative measurements provide useful parameters for
      monitoring of patients. CONCLUSION: There is no consensus on the best technology
      for assessing structural damage in glaucomatous optic neuropathy. Therefore, as
      with any investigation, the clinician should exercise clinical correlation and
      judgment before instituting the appropriate treatment.

PMID- 17450266
TI  - Paradoxical orthodeoxia in a patient with a large thoracic aortic aneurysm.
AB  - INTRODUCTION: Orthodeoxia is a rare clinical syndrome characterised by dyspnoea
      and arterial deoxygenation that accompanies a change from a supine to erect
      position. CLINICAL PICTURE: We describe an unusual case of "paradoxical
      orthodeoxia" in a 70-year-old man with a thoracic aortic aneurysm: arterial
      desaturation when supine that improved when erect. TREATMENT AND OUTCOME: Non
      invasive imaging revealed compression of the left pulmonary artery by the
      aneurysm (thoracic computed tomography) and patent foramen ovale (transesophageal
      echocardiography). Nuclear studies show decreased relative left lung perfusion
      attributable to the former, and right-to-left atrial shunt attributable to the
      latter. The degree of right-to-left shunt increases in the supine position:
      nuclear pulmonary shunt study shows shunt extent of 21% when supine versus 10%
      erect. CONCLUSION: A physioanatomical explanation is proposed.

PMID- 17450267
TI  - A new method for the removal of safety pins ingested by children.
AB  - INTRODUCTION: Foreign body ingestion is a common problem in children. Safety pin
      ingestion is common in Turkey. We describe a new method of removal for safety
      pins in our 2 cases. CLINICAL PICTURE: A 9-month-old girl and a 6-month-old boy
      had each ingested a safety pin. Abdominal X-rays detected the safety pins in
      their stomachs. At the end of 3 months, the foreign bodies still remained in
      their stomachs and laparotomy was indicated. TREATMENT AND OUTCOME: This
      technique consists of a limited midline upper laparotomy with vertical incision.
      Without the utilisation of a gastrotomy, an orogastric tube was inserted into the
      stomach and the open end of the safety pin was pinned to the tube from outside
      the stomach. The orogastric tube was gently pulled out to remove the safety pin.
      CONCLUSION: This method provides shorter hospitalisation time and fewer
      complications.

PMID- 17450268
TI  - Is there a place for placebo in management of psychogenic movement disorders?
AB  - INTRODUCTION: The management of psychogenic movement disorders is fraught with
      difficulties. Empathy and a non-judgmental manner are essential in dealing with
      patients, and a neurobiological explanation of the symptoms may help to foster
      trust, acceptance, understanding and recovery. CLINICAL PICTURE: We report a 17
      year-old Chinese girl with psychogenic blepharospasm. Her parents refused
      psychotherapy and pharmacotherapy. TREATMENT AND OUTCOME: Placebo therapy (with
      parental consent) was prescribed with favourable results. CONCLUSION: We examine
      the ethical considerations for and against placebo therapy, and explore the role
      of placebo therapy in the management of psychogenic movement disorders.

PMID- 17450269
TI  - Cutaneous Kaposi sarcoma which developed in a patient with aplastic anaemia using
      immunosuppressive therapy--description of the first adult case.

PMID- 17450270
TI  - Fatal Clostridium septicaemia associated with massive intravascular haemolysis in
      a previously healthy woman.

PMID- 17450271
TI  - Leptospirosis presenting as acute acalculous cholecystitis and pancreatitis.

PMID- 17450273
TI  - A "tattoo" of erythema multiforme.

PMID- 17450274
TI  - Impacts of air pollution and climate change on forest ecosystems--emerging
      research needs.
AB  - Outcomes from the 22nd meeting for Specialists in Air Pollution Effects on Forest
      Ecosystems "Forests under Anthropogenic Pressure--Effects of Air Pollution,
      Climate Change and Urban Development", September 10-16, 2006, Riverside, CA, are
      summarized. Tropospheric or ground-level ozone (O3) is still the phytotoxic air
      pollutant of major interest. Challenging issues are how to make O3 standards or
      critical levels more biologically based and at the same time practical for wide
      use; quantification of plant detoxification processes in flux modeling; inclusion
      of multiple environmental stresses in critical load determinations; new concept
      development for nitrogen saturation; interactions between air pollution, climate,
      and forest pests; effects of forest fire on air quality; the capacity of forests
      to sequester carbon under changing climatic conditions and coexposure to elevated
      levels of air pollutants; enhanced linkage between molecular biology,
      biochemistry, physiology, and morphological traits.

PMID- 17450275
TI  - Secondary air pollutants and forests--new perspectives.
AB  - Air pollution has been known to affect forests for over a century, and many of
      the mechanisms of pollutant deposition and effects have been established, at
      least for forest trees. Changes in air quality as a result of emission controls
      in Europe and North America, or as a result of rapid industrialisation in
      southern and eastern Asia, have highlighted new pollution problems. This paper,
      by reference to recent publications, highlights two areas where more research is
      required: the interactions of photochemical oxidants with biogenic emissions of
      volatile organic compounds, and their impact on ecological signalling; and the
      role of atmospheric particles in changing the leaf surface environments in
      forests.

PMID- 17450276
TI  - The use of critical levels for determining plant response to ozone in Europe and
      in North America.
AB  - Critical levels to determine plant response to ozone (O3) have been used in
      Europe since the 1980s, utilizing the concentration-based AOT40 to relate plant
      response to ambient O3 exposure. More recently, there has been progress in Europe
      toward utilizing flux-based critical levels, because plant response is more
      closely related to O3 uptake than to the amount of O3 in ambient air. Flux-based
      critical levels are plant species specific; data for parameterization of flux
      based critical levels models are lacking for most plant species. Although flux
      based critical levels are now being used for a limited number of agricultural
      crops and tree species where data are available, the use of flux-based critical
      levels is limited by the lack of adequate consideration and incorporation of
      plant internal detoxification mechanisms in flux modeling. Critical levels have
      not been used in North America; however, recent interest in the U.S. and Canada
      for using critical loads for nitrogen and sulfur has generated interest in using
      critical levels for O3. A major obstacle for utilization of critical levels in
      North America is that ambient air quality standards for O3 in the U.S. and Canada
      are concentration based. It appears that cumulative exposure-based metrics,
      particularly when implemented with a quantification of peak concentrations and
      environmental variables, such as a drought index, are currently the most useful
      to relate O3 to vegetation response. Because data are unavailable to quantify
      detoxification potential of vegetation, effective flux models are not available
      to determine plant response to O3.

PMID- 17450277
TI  - Forest health status in Europe.
AB  - Forest health status in Europe is assessed by the International Cooperative
      Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP
      Forests). Established by the Convention on Long-Range Transboundary Air Pollution
      (CLRTAP) under the United Nations Economic Commission for Europe (UNECE), the ICP
      Forests has been monitoring forest condition in close cooperation with the
      European Commission (EC) for 20 years. The present paper describes the latest
      results of the deposition measurements on permanent monitoring plots and of the
      extensive defoliation sample survey. The findings reveal marked spatial patterns
      in bulk and throughfall depositions of nitrate (N-NO3(-)), ammonium (N-NH4(+)),
      and sulfate (S-SO4(2-)), as well as an obvious decrease in bulk and throughfall
      deposition of sulfate. Latest analyses of defoliation data confirm previous
      results, indicating a high correlation with weather extremes.

PMID- 17450278
TI  - Forest health status in North America.
AB  - The forests of North America provide a variety of benefits including water,
      recreation, wildlife habitat, timber, and other forest products. However, they
      continue to face many biotic and abiotic stressors including fires, native and
      invasive pests, fragmentation, and air pollution. Forest health specialists have
      been monitoring the health of forests for many years. This paper highlights some
      of the most damaging forest stressors affecting North American forests in recent
      years and provides some projections of future risks.

PMID- 17450279
TI  - Trend in ambient ozone and an attempt to detect its effect on biota in forest
      ecosystem. Step I of Lithuanian studies.
AB  - The presented study aimed to explore the relationships between ambient ozone (O3)
      and tree defoliation, specific diversity, and abundance of soil microarthropods,
      stream macroinvertebrates, and small mammals (mainly rodents) in order to test
      the hypothesis that changes in the considered objects of the forest ecosystem
      could be related to changes in ambient O3, concentration of which is below
      critical level. The observations were carried out from 1994 at three integrated
      monitoring stations. The obtained data revealed that only peak O3 concentrations
      (from 125-215 microg x m(-3)) had significant effect on changes in the considered
      components of forest biota.

PMID- 17450280
TI  - Contribution of ambient ozone to changes in Scots pine defoliation. Step II of
      Lithuanian studies.
AB  - This study aimed to explore if changes in peak ozone (O3) concentrations may
      reinforce the phytotoxic effects of air concentration of acidifying compounds and
      their deposition, as well as unfavorable climatic factors on pine crown
      defoliation. Forty-eight pine stands with more than 8000 sample pine trees have
      been monitored annually. The impact of sulfur dioxide (SO2) on pine defoliation
      was found to be the most significant. The impacts of peak O3 concentrations, acid
      deposition, and amount of precipitation were considerably lower, whereas the
      impact of air temperature, the least. Contribution of peak O3 concentrations to
      the integrated impact of acid deposition and amount of precipitation on pine
      defoliation was most significant, whereas the contribution to the impact of
      acidifying air compounds, mainly SO2, was the least. No synergetic effect between
      peak O3 concentrations and high temperature during vegetation period was
      detected.

PMID- 17450281
TI  - Did the ambient ozone affect stem increment of Scots Pines (Pinus sylvestris L.)
      on territories under regional pollution load? Step III of Lithuanian studies.
AB  - This study aimed to explore if changes in stem increment of Scots pines (Pinus
      sylvestris L.) could be related to changes in ambient ozone concentration when
      the impact of tree dendrometric parameters (age, diameter) and crown defoliation
      are accounted for. More than 200 dominant and codominant trees from 12 pine
      stands, for which crown defoliation had been assessed since 1994, were chosen for
      increment boring and basal area increment computing. Stands are located in
      Lithuanian national parks, where since 1994-95 Integrated Monitoring Stations
      have been operating. Findings of the study provide statistical evidence that peak
      concentrations of ambient ozone (O3) can have a negative impact on pine tree stem
      growth under field conditions where O3 exposure is below phytotoxic levels.

PMID- 17450282
TI  - Ozone in Spain's national parks and protected forests.
AB  - In general, it is difficult to measure air pollutant concentrations in remote
      areas, as they are mostly national parks and protected areas. Passive samplers
      provide an accurate and inexpensive method for measuring cumulative exposures of
      different air pollutants. They have been used to collect ozone data in both
      laboratory and field at different geographical scales. The objective of the
      present study is to fill the knowledge gap regarding air quality in remote areas
      of Spain, such as national parks and protected areas. Because there were no
      systematic data sets on the main air pollutants that could affect these areas, an
      air quality measurement network was established between 2001 and 2004 on 19
      locations inside Spanish national parks and protected areas. The data collected
      suggest that ozone levels in mountainous areas are high enough to affect
      sensitive vegetation. Most of the locations registered moderate-to-high ozone
      levels, with important interannual variability. Altitudinal ozone gradients were
      observed in most of the parks with complex topography due to the establishment of
      local circulations that incorporate polluted air masses from polluted airsheds or
      even long-range transport (i.e., Canary Islands). Different latitude-dependent,
      yearly cycles were also observed, showing two, one, or no clear peaks depending
      on the region. These findings extend to the most southerly locations, except in
      the Canary Islands, where pollution transported from other regions in the upper
      transport layers probably led to the high concentrations observed.

PMID- 17450283
TI  - Monitoring of ozone risk for forests in the Czech Republic: preliminary results.
AB  - Ozone (O3) is supposed to represent a significant risk for the health of forest
      ecosystems in Central Europe. So far, however, its impact on stands growing under
      natural conditions has not been clearly proved. A new project of the National
      Agency for the Research in Agriculture is focused on the O3 effect on selected
      parameters of forest health. This paper presents the results of the first year of
      monitoring, 2005. In 2005, high O3 concentrations were measured, mainly in the
      spring. In the summer, due to wet and cold weather, the O3 load was comparatively
      low. In the plots investigated, the concentrations of O3 were higher with the
      altitude. The amount of epicuticular waxes on 1-year-old Norway spruce needles
      was the only factor showing significant correlation to O3 concentration.
      Defoliation of the stands depended only on the stand age. The amount of
      malondialdehyde (MDA), an oxidative stress marker, was related to the altitude,
      and only for European beech. The results are preliminary, as the summer O3
      development was not typical in 2005, and the results may change over the next
      monitoring periods.

PMID- 17450284
TI  - Analysis of climate change affecting German forests by combination of
      meteorological and phenological data within a GIS environment.
AB  - The regional assessment of global change effects on plant phenology usually
      relies on local observations that need to be up-scaled. Therefore, methodological
      difficulties mostly related to data spatial resolution and congruency arise while
      performing broader-scale evaluations. Geostatiscs could be a useful tool to solve
      this type of problem, provided that a database with adequate spatial and temporal
      resolution is available. An assessment of variations in air temperature and plant
      phenology was carried out at the country level by using two German datasets
      regarding spring phenological phases of 15 plant species and air temperature. The
      data were collected from 1961-2002 at 1,279 and 675 sites, respectively. The
      annual mean air temperature in Germany was found to rise from 8.3 degrees C in
      the 1961-1990 period to 9.1 degrees C in the 1991-2002 term. The overall 15
      species mean for the start of spring was found to be 6 days earlier in the latter
      period. The geostatistical analysis of the data revealed the suitability of
      Syringa vulgaris to be used as an indicator species to detect phenological
      changes in German forests. Moreover, their spatial patterns were found to be
      related to altitude and latitude. Therefore, geostatistics proved to be a useful
      tool to overcome some of the methodological problems related to the regional
      assessments of global change impacts on terrestrial ecosystems.

PMID- 17450285
TI  - Visible foliar injury and physiological responses to ozone in Italian provenances
      of Fraxinus excelsior and F. ornus.
AB  - We compared leaf visible injury and physiological responses (gas exchange and
      chlorophyll a fluorescence) to high O3 exposure (150 nmol mol(-1) h, 8 h day(-1),
      35-40 days) of two woody species of the same genus with different ecological
      features: the mesophilic green ash (Fraxinus excelsior) and the xerotolerant
      manna ash (F. ornus). We also studied how provenances from northern (Piedmont)
      and central (Tuscany) Italy, within the two species, responded to O3 exposure.
      Onset and extent of visible foliar injury suggested that F. excelsior was more O3
      sensitive than F. ornus. The higher stomatal conductance in F. ornus than in F.
      excelsior suggested a larger potential O3 uptake, in disagreement to lower
      visible foliar injury. The higher carbon assimilation in F. ornus suggested a
      higher potential of O3 detoxification and/or repair. Contrasting geographical
      variations of ash sensitivity to O3 were recorded, as Piedmont provenances
      reduced gas exchange less than Tuscan provenances in F. excelsior and more in F.
      ornus. Visible injury was earlier and more severe in F. excelsior from Piedmont
      than from Tuscany, while the provenance did not affect visible injury onset and
      extent in F. ornus.

PMID- 17450286
TI  - Air pollution distribution patterns in the San Bernardino Mountains of southern
      California: a 40-year perspective.
AB  - Since the mid-1950s, native pines in the San Bernardino Mountains (SBM) in
      southern California have shown symptoms of decline. Initial studies in 1963
      showed that ozone (O3) generated in the upwind Los Angeles Basin was responsible
      for the injury and decline of sensitive trees. Ambient O3 decreased significantly
      by the mid-1990s, resulting in decreased O3 injury and improved tree growth.
      Increased growth of trees may also be attributed to elevated atmospheric nitrogen
      (N) deposition. Since most of the N deposition to mixed conifer forest stands in
      the SBM results from dry deposition of nitric acid vapor (HNO3) and ammonia
      (NH3), characterization of spatial and temporal distribution of these two
      pollutants has become essential. Although maximum daytime O3 concentrations over
      last 40 years have significantly decreased (approximately 3-fold), seasonal means
      have been reduced much less (approximately 1.5-fold), with 2-week long means
      occasionally exceeding 100 ppb in the western part of the range. In the same
      area, significantly elevated concentrations of HNO3 and NH3, up to 17.5 and 18.5
      microg/m3 as 2-week averages, respectively, have been determined. Elevated levels
      of O3 and increased N deposition together with long-term drought predispose the
      SBM forests to massive bark beetle attacks making them susceptible to
      catastrophic fires.

PMID- 17450287
TI  - Alterations of the biochemical pathways of plants by the air pollutant ozone:
      which are the true gauges of injury?
AB  - Plant strategies to survive ozone stress include exclusion or tolerance of ozone.
      If these processes fail, past observations of ozone injury have indicated many
      physiological and metabolic changes then occur; most of these changes are likely
      to have been initiated at the level of gene expression, suggesting signal
      transduction. In the last decade considerable understanding of the biochemical
      process within plants has been developed. Currently there are several hypotheses
      regarding a response of plants to ozone fumigation: [1] membrane dysfunction and
      alteration of purpose; [2] stress ethylene interactions; [3] impairment of
      photosynthesis via changes in Rubisco levels and the guard cells so that the
      stomata do not track correctly the environment; [4] antioxidant protection
      through metabolites and enzyme systems to reduce the oxidant load; and [5]
      general impairment or disruption of metabolic pathways. Many believe that free
      radicals and other oxidative products, formed in plant leaves under ozone
      exposure, are responsible for much of the spread of the biochemical alterations.
      There are obvious chemicals that may account for the changes that are observed,
      such as hydrogen peroxide. Once the ozone enters the tissue, evidence suggests
      the first line of defense is a range of antioxidants, such as ascorbate,
      glutathione peroxidase, superoxide dismutase, and catalase. If overwhelmed,
      subsequent events occur which are highly suggestive of systemic acquired
      resistance. Furthermore, other defensive indicators, such as salicylic acid and
      jasmonic acid, tend to increase, but more slowly than ethylene, and spread their
      signaling effects more widely in the plant. The primary set of metabolic
      reactions that ozone triggers is thought to be "wounding" responses with a
      secondary response of senescence. The dramatic strides in understanding the
      genetic make-up of plants, gene control, and signal transduction/control over the
      last few years will only accelerate in the future. We need now to have an
      understanding of those events that can be translated into more detailed schemes
      of how ozone alters much of the basic metabolism of plants and how plants
      counteract or cope with ozone. What is now known about how varied biochemicals
      and their pathways are changed upon ozone exposure will be discussed.

PMID- 17450288
TI  - Parameterization of the stomatal component of the DO3SE model for Mediterranean
      evergreen broadleaf species.
AB  - An ozone (O3) deposition model (DO3SE) is currently used in Europe to define the
      areas where O3 concentrations lead to absorbed O3 doses that exceed the flux
      based critical levels above which phytotoxic effects would be likely recorded.
      This mapping exercise relies mostly on the accurate estimation of O3 flux through
      plant stomata. However, the present parameterization of the modulation of
      stomatal conductance (g(s)) behavior by different environmental variables needs
      further adjustment if O3 phytotoxicity is to be assessed accurately at regional
      or continental scales. A new parameterization of the model is proposed for Holm
      oak (Quercus ilex), a tree species that has been selected as a surrogate for all
      Mediterranean evergreen broadleaf species. This parameterization was based on a
      literature review, and was calibrated and validated using experimentally measured
      data of g(s) and several atmospheric and soil parameters recorded at three sites
      of the Iberian Peninsula experiencing long summer drought, and very cold and dry
      winter air (El Pardo and Miraflores) or milder conditions (Tietar). A fairly good
      agreement was found between modeled and measured data (R2 = 0.64) at Tietar.
      However, a reasonable performance (R2 = 0.47-0.62) of the model was only achieved
      at the most continental sites when g(s) and soil moisture deficit relationships
      were considered. The influence of root depth on g(s) estimation is discussed and
      recommendations are made to build up separate parameterizations for continental
      and marine-influenced Holm oak sites in the future.

PMID- 17450289
TI  - Ethylenediurea (EDU) affects the growth of ozone-sensitive and tolerant ash
      (Fraxinus excelsior) trees under ambient O3 conditions.
AB  - Adult ash trees (Fraxinus excelsior L.), known to be sensitive or tolerant to
      ozone, determined by presence or absence of foliar symptoms in previous years,
      were treated with ethylenediurea (EDU) at 450 ppm by gravitational trunk infusion
      over the 2005 growing season (32.5 ppm h AOT40). Tree and shoot growth were
      recorded in May and September. Leaf area, ectomycorrhizal infection, and leaf and
      fine root biomass were determined in September. EDU enhanced shoot length and
      diameter, and the number and area of leaves, in both O3-sensitive and tolerant
      trees. However, no EDU effects were recorded at the fine root and tree level.
      Therefore, a potential for EDU protection against O3-caused growth losses of
      forest trees should be evaluated during longer-term experiments.

PMID- 17450290
TI  - Chronic vs. short-term acute O3 exposure effects on nocturnal transpiration in
      two Californian oaks.
AB  - We tested the effect of daytime chronic moderate ozone (O3) exposure, short-term
      acute exposure, and both chronic and acute O3 exposure combined on nocturnal
      transpiration in California black oak and blue oak seedlings. Chronic O3 exposure
      (70 ppb for 8 h/day) was implemented in open-top chambers for either 1 month
      (California black oak) or 2 months (blue oak). Acute O3 exposure (approximately 1
      h in duration during the day, 120-220 ppb) was implemented in a novel gas
      exchange system that supplied and maintained known O3 concentrations to a leaf
      cuvette. When exposed to chronic daytime O3 exposure, both oaks exhibited
      increased nocturnal transpiration (without concurrent O3 exposure) relative to
      unexposed control leaves (1.8x and 1.6x, black and blue oak, respectively). Short
      term acute and chronic O3 exposure did not further increase nocturnal
      transpiration in either species. In blue oak previously unexposed to O3, short
      term acute O3 exposure significantly enhanced nocturnal transpiration (2.0x)
      relative to leaves unexposed to O3. California black oak was unresponsive to
      (only) short-term acute O3 exposure. Daytime chronic and/or acute O3 exposures
      can increase foliar water loss at night in deciduous oak seedlings.

PMID- 17450291
TI  - Changes in the essential oil composition in the needles of Scots pine (Pinus
      sylvestris L.) under anthropogenic stress.
AB  - Unfavorable anthropogenic factors, such as air pollution, lead to biochemical
      responses in trees. Changes in the amounts of secondary metabolites may be early
      indicators of invisible injuries. The aim of this study was to evaluate
      composition of the essential oils in the needles of Scots pine (Pinus sylvestris
      L.) growing in the areas affected by pollutant emissions of main factories in
      Lithuania: a nitrogen fertilizer factory (NFF), a cement factory (CF), and an oil
      refinery (OR). Totally, 14 pine stands were examined along transects from the
      factories (July 2005). Volatile components of the needles were extracted and
      analyzed by GC and GC/MS. Over 70 components of the essential oils were
      identified in current-year and 1-year-old needles. Along the CF transect for
      current-year needles, the percentage of diterpenes was decreasing with the
      increasing pH of the pine bark (r = -0.582; p < 0.05) or with the increasing
      concentration of SO2 (r = -0.573; p < 0.05); for 1-year-old needles, the
      percentage of diterpenes was decreasing with the increasing pH of the bark (r = 
      0.534; p < 0.05). Along the OR transect, in both the current-year and 1-year-old
      needles, the percentage of diterpenes was decreasing with the increasing SO2
      (respectively, r = -0.773; p < 0.01; r = -0.486; p < 0.05); an opposite relation
      was true for sesquiterpenes (respectively, r = -0.751; p < 0.01; r = 0.785; p <
      0.01). The view was different along the NFF transect. For current-year needles,
      the percentage of monoterpenes was decreasing with the increasing NH3 (r = 
      0.669; p < 0.01); while the percentage of sesquiterpenes or oxysesquiterpenes was
      increasing with the increasing NH3 (respectively, r = 0.540; p < 0.05 and r =
      0.688; p < 0.01). For each transect, cluster analysis of the percentages of
      components of essential oils in the needles allowed us to distinguish the most
      contrasting stands according to the concentration of air pollutants. Current-year
      needles were more effective as indicators of the effects of pollution than 1-year
      old needles in the case of the NFF and the OR transects, and both-aged needles
      were equally valuable in the case of the CF transect. The changes detected in the
      proportions of components of the essential oils in the needles of the trees
      affected by the industrial emissions may play a significant role in modifying the
      susceptibility of the pine stands to the biotic factors, and also may alter
      emissions of terpenes from the stands to the atmosphere.

PMID- 17450292
TI  - Nitrogen accumulation in forests. Exposure monitoring by mosses.
AB  - At present, there is still little information on nitrogen (N) accumulation in
      forests contrasting with the crucial importance of N in forest ecosystems. This
      work analyzes the N bioaccumulation in mosses from forested areas from Lower
      Saxony and North Rhine-Westphalia (two of 16 federal states of Germany), the
      Weser Ems Region (part of Lower Saxony), and the Euro Region Nissa (covering the
      Czech Republic, Germany, Poland). The studies involved samples collected from 190
      sites between 1998 and 2005. Different spatial scales and regional differences in
      land use were chosen to assess the factors affecting N bioaccumulation in
      forested areas. A continuous reduction of N bioaccumulation was found from Lower
      Saxony (a region where agriculture is most predominant) to North Rhine-Westphalia
      (mostly urban). The Weser Ems Region (an agricultural region) showed a higher N
      concentration in mosses than the Euroregion Nissa (a former industrial region).
      Statistical analyses performed at the different spatial scales revealed that the
      areas showing greater agricultural and livestock spatial densities favor N
      bioaccumulation in mosses. N concentration in mosses was moderately correlated
      with the N concentration in the leaves and needles of the surrounding trees. No
      significant relationships were found regarding the crown density of forest trees
      or N deposition estimations from a combination of atmospheric models and
      deposition measurements.

PMID- 17450294
TI  - Soil CO2 efflux in a mixed pine-oak forest in Valsain (central Spain).
AB  - Soil-surface CO2 efflux and its spatial and temporal variation were investigated
      in a southern Mediterranean, mixed pine-oak forest ecosystem on the northern
      slopes of the Sierra de Guadarrama in Spain from February 2006 to July 2006.
      Measurements of soil CO2 efflux, soil temperatures, and moisture were conducted
      in nine 1963-m2 sampling plots distributed in a gradient around the ecotone
      between Pinus sylvestris L. and Quercus pyrenaica Lam. forest stands. Total soil
      organic matter, Walkey-Black C, particulate organic matter, organic matter
      fraction below 53 microm, total soil nitrogen content, total soil organic carbon
      content, and pH were also measured under three representative mature oak, pine,
      and mixed pine-oak forest stands. Soil respiration showed a typical seasonal
      pattern with minimums in winter and summer, and maximums in spring, more
      pronounced in oak and oak-pine stands. Soil respiration values were highest in
      pine stands during winter and in oak stands during spring and summer. Soil
      respiration was highly correlated with soil temperatures in oak and pine-oak
      stands when soil moisture was above a drought threshold of 15%. Below this
      threshold value, soil moisture was a good predictor of soil respiration in pine
      stands. Greater soil organic matter, particulate organic matter, Walkey-Black C,
      total organic C, and total N content in pine compared to oak sites potentially
      contributed to the greater total soil CO2 efflux in these stands during the
      winter. Furthermore, opposing trends in the organic matter fraction below 53
      microm and soil respiration between plots suggest that in oak stands, the C forms
      are less affected by possible changes in use. The effects of soil properties on
      soil respiration were masked by differences in soil temperature and moisture
      during the rest of the year. Understanding the spatial and temporal variation
      even within small geographic areas is essential to assess C budgets at ecosystem
      level accurately. Thus, this study bears important implications for the study of
      large-scale ecosystem dynamics, particularly in response to climatic change.

PMID- 17450293
TI  - Modeling of nitrogen dynamics in an Austrian alpine forest ecosystem on
      calcareous soils: a scenario-based risk assessment under changing environmental
      conditions.
AB  - We modeled the behavior of an Austrian alpine forest ecosystem on calcareous
      soils under changing climate and atmospheric nitrogen deposition scenarios. The
      change of nitrate leaching, emission rates of nitrogen compounds, and forest
      productivity were calculated using four process-oriented models for the periods
      1998-2002 and 2048-2052. Each model reflects with high detail a segment of the
      ecosystem: PnET-N-DNDC (photosynthesis-evapotranspiration-nitrification
      denitrification-decomposition; short-term nitrogen cycling), BROOK90 (water
      balance for small and homogenous forest watersheds), HYDRUS (water flux in
      complex and heterogenous soils), and PICUS v1.3 (forest productivity). The
      nitrogen balance model (NBM) combines the individual results into a comprehensive
      picture and extends the specific values beyond the limits of the individual
      models. The evaluation of the findings was outlined with TRACE, a model enabling
      a long-term prognosis of nitrogen cycling in annual time steps. Temperature
      increase and nitrogen input are influenced by various components and processes of
      the forest ecosystem. An increase of the temperature of 2.5 degrees C led to an
      enhancement of the N2O emission rates and affected the mineralization and the
      nitrification rates with the consequence of increased nitrate leaching into the
      subsoil. Enhanced nitrogen input also showed notable effects on nitrate leaching.

PMID- 17450295
TI  - Smog nitrogen and the rapid acidification of forest soil, San Bernardino
      Mountains, southern California.
AB  - We report the rapid acidification of forest soils in the San Bernardino Mountains
      of southern California. After 30 years, soil to a depth of 25 cm has decreased
      from a pH (measured in 0.01 M CaCl2) of 4.8 to 3.1. At the 50-cm depth, it has
      changed from a pH of 4.8 to 4.2. We attribute this rapid change in soil
      reactivity to very high rates of anthropogenic atmospheric nitrogen (N) added to
      the soil surface (72 kg ha(-1) year(-1)) from wet, dry, and fog deposition under
      a Mediterranean climate. Our research suggests that a soil textural
      discontinuity, related to a buried ancient landsurface, contributes to this rapid
      acidification by controlling the spatial and temporal movement of precipitation
      into the landsurface. As a result, the depth to which dissolved anthropogenic N
      as nitrate (NO3) is leached early in the winter wet season is limited to within
      the top approximately 130 cm of soil where it accumulates and increases soil
      acidity.

PMID- 17450296
TI  - The effect of stand age on throughfall chemistry in spruce stands in the Potok
      Dupnianski catchment in the Silesian Beskid Mountains, southern Poland.
AB  - The chemical composition of throughfall depends on the age of the Norway spruce
      (Picea abies Karst) stands and season of the year. The pH of throughfall
      decreased and the amount of hydrogen ion in throughfall deposited to the soil
      increased with increasing age of spruce stands, especially in the winter season.
      Concentrations of K+, H+, SO4(2-), Mn2+, and NH4(+) in throughfall were higher
      than bulk precipitation for the whole year and K+, H+, and Mn2+ concentrations
      were higher in throughfall in winter and the growing season. This indicates that
      these ions were washed out or washed from the surface of needles and/or the bark,
      and that NO3(-), NH4(+), Ca2+, Mg2+, Fe2+, and Zn2+ were absorbed in the canopy.
      The effect of high nitrogen deposition, above critical loads, and an increase in
      the amount of sulfur and in the sum of the strong acids (S-SO4(2-) and N-NO3(-))
      that reached the soil with throughfall may have implications for the vitality of
      spruce stands, especially in older age classes. The application of Principal
      Component Analysis (PCA) has led to identification of five factors responsible
      for the data structure ("mineral dust", "acidic emissions", "heavy metals-dust
      particles", "ammonium [NH4(+)]", and "H+"). They explain more than 60% of the
      total variance system. The strong positive correlation between stand age class
      and ionic concentrations in throughfall occurs for all year and the winter period
      for ions within the following categories: "acidic emissions", SO4(2-) + NO3(-);
      "heavy metals-dust particles", Fe2+ + Mn2+ + Zn2+; "mineral dust", Na+ + K+ +
      Ca2+ + Mg2+; "NH4(+)"; and "H+". The strength of the relationship decreases in
      the growing period, probably due to processes occurring in the canopy
      (adsorption, leaching, etc.).

PMID- 17450297
TI  - Atmospheric heavy metal input to forest soils in rural areas of Denmark.
AB  - Atmospheric bulk deposition of heavy metals (HM) was measured from 1972/73 to the
      present time at five to ten forest sites in rural areas of Denmark. From 1979, HM
      in aerosols were measured at one to four forest sites. On the basis of these long
      term continuous measurements, the atmospheric inputs to the forest floor have
      been calculated. Yearly HM emission estimates to the European atmosphere seems to
      correlate well with yearly average values of HM deposition, as well as with HM
      concentrations in the ambient atmosphere. HM emissions have been estimated since
      the 1950s. Using the correlation between emission and deposition, HM deposition
      values maybe extrapolated in reverse chronological order. The accumulated
      atmospheric HM deposition has been estimated in this way over a period of 50
      years.

PMID- 17450298
TI  - Calculation of theoretical and empirical nutrient N critical loads in the mixed
      conifer ecosystems of southern California.
AB  - Edaphic, foliar, and hydrologic forest nutrient status indicators from 15 mixed
      conifer forest stands in the Sierra Nevada, San Gabriel Mountains, and San
      Bernardino National Forest were used to estimate empirical or theoretical
      critical loads (CL) for nitrogen (N) as a nutrient. Soil acidification response
      to N deposition was also evaluated. Robust empirical relationships were found
      relating N deposition to plant N uptake (N in foliage), N fertility (litter C/N
      ratio), and soil acidification. However, no consistent empirical CL were obtained
      when the thresholds for parameters indicative of N excess from other types of
      ecosystems were used. Similarly, the highest theoretical CL for nutrient N
      calculated using the simple mass balance steady state model (estimates ranging
      from 1.4-8.8 kg N/ha/year) was approximately two times lower than the empirical
      observations. Further research is needed to derive the thresholds for indicators
      associated with the impairment of these mixed conifer forests exposed to chronic
      N deposition within a Mediterranean climate. Further development or
      parameterization of models for the calculation of theoretical critical loads
      suitable for these ecosystems will also be an important aspect of future critical
      loads research.

PMID- 17450299
TI  - Air pollution and watershed research in the central Sierra Nevada of California:
      nitrogen and ozone.
AB  - Maintaining healthy forests is the major objective for the Forest Service
      scientists and managers working for the U.S. Department of Agriculture. Air
      pollution, specifically ozone (O3) and nitrogenous (N) air pollutants, may
      severely affect the health of forest ecosystems in the western U.S. Thus, the
      monitoring of air pollution concentration and deposition levels, as well as
      studies focused on understanding effects mechanisms, are essential for evaluation
      of risks associated with their presence. Such information is essential for
      development of proper management strategies for maintaining clean air, clean
      water, and healthy ecosystems on land managed by the Forest Service. We report on
      two years of research in the central Sierra Nevada of California, a semi-arid
      forest at elevations of 1100-2700 m. Information on O3 and N air pollutants is
      obtained from a network of 18 passive samplers. We relate the atmospheric N
      concentration to N concentrations in streams, shallow soil water, and bulk
      deposition collectors within the Kings River Experimental Watershed. This
      watershed also contains an intensive site that is part of a recent Forest Service
      effort to calculate critical loads for N, sulfur, and acidity to forest
      ecosystems. The passive sampler design allows for extensive spatial measurements
      while the watershed experiment provides intensive spatial data for future
      analysis of ecosystem processes.

PMID- 17450300
TI  - Pre-exposure to ozone predisposes oak leaves to attacks by Diplodia corticola and
      Biscogniauxia mediterranea.
AB  - One-year-old cork oak (Quercus suber) and turkey oak (Q. cerris) seedlings were
      exposed to ozone (110 ppb, 5 h day(-1), for 30 days) and were inoculated with
      Diplodia corticola and Biscogniauxia mediterranea, respectively, by spraying a
      suspension of spores on the leaves. Both fungi are endophytic and may act as weak
      parasites, contributing to oak decline. Ozone exposure stimulated leaf attacks
      after inoculation, although the physiological, visible, and structural responses
      of both oaks to O3 exposure were weak. In fact, steady-state gas exchange, leaf
      waxes, and wettability were not significantly affected by O3. In Q. cerris, O3
      altered the structure of stomata, as observed by scanning microscopy, and reduced
      the leaf relative water content. No hyphal entry through stomata or growth
      towards stomata was, however, observed. Inoculations were performed in a humid
      chamber at low light; stomata were likely to be closed. When Q. cerris was
      inoculated in natural conditions, i.e., in a forest infected by B. mediterranea,
      seedlings pre-exposed to the enhanced O3 regime had a higher number of B.
      mediterranea isolates than the controls. This suggests that pre-exposure to O3
      predisposed Q. cerris leaves to attacks by B. mediterranea independent of
      stomata. The hyphae of both fungi were able to enter the leaf through the
      cuticle, either by gradual in-growth into the cuticle or erosion of a hollow in
      the cuticle at the point of contact. The primary cause of increased leaf injury
      in O3-exposed seedlings appeared to be higher germination of spores than on
      control leaves.

PMID- 17450301
TI  - Linking increasing drought stress to Scots pine mortality and bark beetle
      infestations.
AB  - In the dry Swiss Rhone Valley, Scots pine forests have experienced increased
      mortality in recent years. It has commonly been assumed that drought events and
      bark beetles fostered the decline, however, whether bark beetle outbreaks
      increased in recent years and whether they can be linked to drought stress or
      increasing temperature has never been studied. In our study, we correlated time
      series of drought indices from long-term climate stations, 11-year mortality
      trends from a long-term research plot, and mortality probabilities modeled from
      tree rings (as an indicator of tree vitality) with documented occurrences of
      various bark beetle species and a buprestid beetle, using regional Forest Service
      reports from 1902 to 2003 and advisory cases of the Swiss Forest Protection
      Service (SFPS) from 1984 to 2005. We compared the historical findings with
      measured beetle emergence from a 4-year tree felling and breeding chamber
      experiment. The documented beetle-related pine mortality cases increased
      dramatically in the 1990s, both in the forest reports and the advisory cases. The
      incidents of beetle-related pine mortality correlated positively with spring and
      summer temperature, and with the tree-ring based mortality index, but not with
      the drought index. The number of advisory cases, on the other hand, correlated
      slightly with summer drought index and temperature, but very highly with tree
      ring-based mortality index. The tree-ring-based mortality index and observed tree
      mortality increased in years following drought. This was confirmed by the beetle
      emergences from felled trees. Following dry summers, more than twice as many
      trees were colonized by beetles than following wet summers. We conclude that
      increased temperatures in the Swiss Rhone Valley have likely weakened Scots pines
      and favored phloeophagous beetle population growth. Beetles contributed to the
      increased pine mortality following summer drought. Among the factors not
      addressed in this study, changed forest use may have also contributed to
      increased beetle populations and Scots pine mortality, whereas air pollution
      seems to be of lesser importance.

PMID- 17450302
TI  - Impacts of elevated atmospheric CO2 and O3 on paper birch (Betula papyrifera):
      reproductive fitness.
AB  - Atmospheric CO2 and tropospheric O3 are rising in many regions of the world.
      Little is known about how these two commonly co-occurring gases will affect
      reproductive fitness of important forest tree species. Here, we report on the
      long-term effects of CO2 and O3 for paper birch seedlings exposed for nearly
      their entire life history at the Aspen FACE (Free Air Carbon Dioxide Enrichment)
      site in Rhinelander, WI. Elevated CO2 increased both male and female flower
      production, while elevated O3 increased female flower production compared to
      trees in control rings. Interestingly, very little flowering has yet occurred in
      combined treatment. Elevated CO2 had significant positive effect on birch catkin
      size, weight, and germination success rate (elevated CO2 increased germination
      rate of birch by 110% compared to ambient CO2 concentrations, decreased seedling
      mortality by 73%, increased seed weight by 17%, increased root length by 59%, and
      root-to-shoot ratio was significantly decreased, all at 3 weeks after
      germination), while the opposite was true of elevated O3 (elevated O3 decreased
      the germination rate of birch by 62%, decreased seed weight by 25%, and increased
      root length by 15%). Under elevated CO2, plant dry mass increased by 9 and 78% at
      the end of 3 and 14 weeks, respectively. Also, the root and shoot lengths, as
      well as the biomass of the seedlings, were increased for seeds produced under
      elevated CO2, while the reverse was true for seedlings from seeds produced under
      the elevated O3. Similar trends in treatment differences were observed in seed
      characteristics, germination, and seedling development for seeds collected in
      both 2004 and 2005. Our results suggest that elevated CO2 and O3 can dramatically
      affect flowering, seed production, and seed quality of paper birch, affecting
      reproductive fitness of this species.

PMID- 17450303
TI  - Patterns of understory diversity in mixed coniferous forests of southern
      California impacted by air pollution.
AB  - The forests of the San Bernardino Mountains have been subject to ozone and
      nitrogen (N) deposition for some 60 years. Much work has been done to assess the
      impacts of these pollutants on trees, but little is known about how the diverse
      understory flora has fared. Understory vegetation has declined in diversity in
      response to elevated N in the eastern U.S. and Europe. Six sites along an ozone
      and N deposition gradient that had been part of a long-term study on response of
      plants to air pollution beginning in 1973 were resampled in 2003. Historic ozone
      data and leaf injury scores confirmed the gradient. Present-day ozone levels were
      almost half of these, and recent atmospheric N pollution concentrations confirmed
      the continued air pollution gradient. Both total and extractable soil N were
      higher in sites on the western end of the gradient closer to the urban source of
      pollution, pH was lower, and soil carbon (C) and litter were higher. The gradient
      also had decreasing precipitation and increasing elevation from west to east.
      However, the dominant tree species were the same across the gradient. Tree basal
      area increased during the 30-year interval in five of the sites. The two
      westernmost sites had 30-45% cover divided equally between native and exotic
      understory herbaceous species, while the other sites had only 3-13% cover
      dominated by native species. The high production is likely related to higher
      precipitation at the western sites as well as elevated N. The species richness
      was in the range of 24 to 30 in four of the sites, but one site of intermediate N
      deposition had 42 species, while the easternmost, least polluted site had 57
      species. These were primarily native species, as no site had more than one to
      three exotic species. In three of six sites, 20-40% of species were lost between
      1973 and 2003, including the two westernmost sites. Two sites with intermediate
      pollution had little change in total species number over 30 years, and the
      easternmost site had more species in 2003. The easternmost site is also the
      driest and has the most sunlight filtering to the forest floor, possibly
      accounting for the higher species richness. The confounding effects of the
      precipitation gradient and possibly local disturbances do not show a simple
      correlation of air pollution with patterns of native and invasive species cover
      and richness. Nevertheless, the decline of native species and dominance by exotic
      species in the two westernmost polluted sites is cause for concern that air
      pollution is affecting the understory vegetation adversely.

PMID- 17450305
TI  - Collagen structure of tendon relates to function.
AB  - A tendon is a tough band of fibrous connective tissue that connects muscle to
      bone, designed to transmit forces and withstand tension during muscle
      contraction. Tendon may be surrounded by different structures: 1) fibrous sheaths
      or retinaculae; 2) reflection pulleys; 3) synovial sheaths; 4) peritendon
      sheaths; 5) tendon bursae. Tendons contain a) few cells, mostly represented by
      tenoblasts along with endothelial cells and some chondrocytes; b) proteoglycans
      (PGs), mainly decorin and hyaluronan, and c) collagen, mostly type I. Tendon is a
      good example of a high ordered extracellular matrix in which collagen molecules
      assemble into filamentous collagen fibrils (formed by microfibrils) which
      aggregate to form collagen fibers, the main structural components. It represents
      a multihierarchical structure as it contains collagen molecules arranged in
      fibrils then grouped in fibril bundles, fascicles and fiber bundles that are
      almost parallel to the long axis of the tendon, named as primary, secondary and
      tertiary bundles. Collagen fibrils in tendons show prevalently large diameter, a
      D-period of about 67 nm and appear built of collagen molecules lying at a slight
      angle (< 5 degrees). Under polarized light microscopy the collagen fiber bundles
      appear crimped with alternative dark and light transverse bands. In recent
      studies tendon crimps observed via SEM and TEM show that the single collagen
      fibrils suddenly changing their direction contain knots. These knots of collagen
      fibrils inside each tendon crimp have been termed "fibrillar crimps", and even if
      they show different aspects they all may fulfil the same functional role. As
      integral component of musculoskeletal system, the tendon acts to transmit muscle
      forces to the skeletal system. There is no complete understanding of the
      mechanisms in transmitting/absorbing tensional forces within the tendon; however
      it seems likely that a flattening of tendon crimps may occur at a first stage of
      tendon stretching. Increasing stretching, other transmission mechanisms such as
      an interfibrillar coupling via PGs linkages and a molecular gliding within the
      fibrils structure may be involved.

PMID- 17450306
TI  - Dissociated steroids.
AB  - Glucocorticoids (GCs) are some of the most important drugs in clinical use today.
      They are mainly used to suppress disease-related inflammation and are widely used
      for the treatment of many inflammatory diseases including asthma and arthritis.
      However, GCs are also associated with debilitating side effects that place
      limitations on the long-term use of these drugs. The development of a GC with
      reduced side effects would allow more effective treatments for patients who
      require long-term suppression of inflammation. GCs exert their effects by binding
      and activating the GC receptor (GR). The activated receptor then binds GC
      response elements (GREs) in the promoter of genes, and activates transcription
      (transactivation) or interferes with the activation of transcription by
      inhibiting the transactivating function of other transcription factors, such as
      AP-1 and NF-kB (transrepression). Transrepression is believed to be responsible
      for the majority of the beneficial anti-inflammatory effects of GCs, whereas
      transactivation is believed to play a bigger role in the unwanted side effects of
      GCs. Compounds that can dissociate the transactivation function of GCs from the
      transrepression function may, therefore, have an improved therapeutic index. A
      number of these dissociated corticosteroids have been developed. In vitro assays
      using these compounds appear to show good dissociation. However, in vivo, the
      dissociation appears to be lost and these compounds still produce many of the
      side effects associated with conventional GCs. A better understanding of the
      molecular mechanisms behind GC-induced effects would allow the design of novel
      selective GR modulators with an improved therapeutic index.

PMID- 17450307
TI  - TNF-alpha as a therapeutic target in acute pancreatitis--lessons from
      experimental models.
AB  - A considerable body of experimental evidence suggests that tumor necrosis factor
      (TNF)-a plays a major role in several aspects of inflammation and shock. In
      particular, it is pivotal in many detrimental effects of acute pancreatitis, and
      it represents a major determinant of the systemic progression and end-organ
      damage (such as acute lung injury and liver failure) of this pathologic
      condition. Given the importance of TNF-a in the pathogenesis of acute
      pancreatitis, investigators have regarded blocking the action of this mediator as
      an attractive treatment option. Different specific and nonspecific inhibitors
      have been developed with promising results in animal models, but, on the other
      hand, no clinical trials have been designed so far. Difficulties in clinical
      applications may be multifactorial; experimental models are not fully reliable
      and reproduce at least some aspects of human disease, timing of intervention
      should be related to changes in TNF-a serum levels, and inclusion criteria should
      be accurately selected to better define the population most likely to benefit.

PMID- 17450308
TI  - Narrow-band imaging in digestive endoscopy.
AB  - The application of opto-electronics in video-endoscopes improves the accuracy in
      diagnosis, through image processing and digital technology. Narrow Band Imaging
      (NBI), consists of using interference filters for the illumination of the target
      in narrowed blue and green bands of the spectrum. NBI is combined with magnifying
      endoscopy using an objective macro or an optical zoom. The NBI technique
      developed by Olympus Medical Systems is now available in the most recent models
      of video-endoscopes that use the non-sequential system of illumination (Lucera
      Spectrum) or the sequential R/G/B system of illumination (Exera II). The major
      contribution of the technique is in the characterization (analysis after
      detection) of the flat and superficial neoplastic areas of the digestive mucosa,
      with a specific application to the identification of intestinal metaplasia and
      early neoplastic changes in the Barrett's esophagus. The technique also proves
      helpful for the assessment of the vascular pattern in chronic inflammatory
      disorders of the digestive mucosa.

PMID- 17450309
TI  - A potential concept in the management of tumors with modulation of prostaglandin,
      nitric oxide and antioxidants.
AB  - Prostaglandins (PGs), nitric oxide (NO), free radicals and chronic inflammation
      play a major role in tumorogenesis. We have found in vivo that PGs suppress
      antibody production; reduce serum iron, and modulate bone marrow function. Tumors
      are associated with immunosuppression and anemia. We have hypothesized that the
      over-production of PGs is responsible for immunosuppression and anemia in
      conditions associated with increased production of PG such as tumor, and that PG
      inhibitors might help reversing immunosuppression and anemia, and play a role in
      eradication and prevention of tumors. This is supported by reports that
      demonstrate the immunosuppressive effects of PGs in tumors. PG inhibitors have
      also been shown to be crucial in the prevention of tumors such as esophageal and
      colon cancers. Others and we have found that high NO production was encountered
      in patients with cancer while antioxidants are decreased. Evidence supports the
      efficacy of PG inhibition in malignancies, and the concept of PG inhibition, NO
      modulation, anti-oxidants, immunotherapy with antibody or immune cells, and anti
      inflammatory agents when used in the prevention and management of malignancies
      are discussed.

PMID- 17450310
TI  - The status of childhood lead poisoning and prevention in Nevada, USA.
AB  - One of the first steps in addressing the problem of childhood lead poisoning is
      to identify the possible sources of exposure in specific communities and target
      high-risk populations with appropriate interventions. Due to several factors,
      such as lack of funding and lack of blood lead reporting, little information
      exists regarding the occurrence of childhood lead poisoning and the prevalence of
      potential exposure sources in the state of Nevada. Following the recent
      establishment of a Nevada-based Lead Poisoning Program, we compiled the most
      current information available on Nevadans, and use this knowledge to suggest
      future research objectives and outreach activities for the state. Accordingly, we
      identify the characteristics of the vulnerable Nevada populations, explore
      possible sources of lead exposure unique to Nevada, and summarize the existing
      data on childhood lead poisoning. Emerging data indicates that Nevada is an area
      of rapid population growth, characterized by increasing immigration from Latin
      America, increasing numbers of children from low-income families with no health
      insurance. Also, childhood lead poisoning may arise from exposure to non-paint
      sources of lead. After presenting the Nevada statistics, we propose and recommend
      a set of research and outreach strategies that best suit the needs of Nevada
      residents.

PMID- 17450311
TI  - The determinants of sexual intercourse before age 16 years among rural Jamaican
      adolescents.
AB  - Individual and family factors have been hypothesized to influence adolescent
      sexual behavior, but the extent to which this is true for adolescents in Jamaica
      as a whole and for those in rural areas in particular, has not been well studied.
      The objective of this study was to identify individual and family factors
      associated with initiation of sexual activity before the age of 16 among rural
      adolescents in Jamaica. We analyzed data for 469 sexually experienced adolescents
      attending public high schools in the rural parish of Hanover. Multivariate
      logistic regression was used to predict independent influences of these factors.
      The mean age at sexual debut was 11 years for boys and 15 years for girls. Early
      adolescent sexual activity was associated with liberal attitudes about negative
      sexual outcomes (OR = 1.96, 95%CI = 1.34-2.87) and first sexual partner not being
      a steady boyfriend or girlfriend (OR = 4.19, 95%CI = 1.62-10.84). Female gender
      (OR = 0.16, 95%CI = 0.07-0.36) and older age at time of survey were protective
      (OR = 0.40, 95%CI = 0.32-0.52). Girls who were early starters were more likely to
      have been initiated by partners who were not steady boyfriends. They also
      reported liberal attitude towards negative sexual outcomes. Boys were mainly
      influenced by liberal attitude towards negative sexual outcomes. Being older was
      protective for both genders. Considering the high rates of HIV and adolescent
      pregnancy in this population, reproductive health programs that attempt to delay
      age at first sex should begin early in primary school before adolescents become
      sexually active.

PMID- 17450312
TI  - Massive steinstrasse after treatment of a staghorn calculus.

PMID- 17450313
TI  - Level and distribution of polychlorinated biphenyls (PCBs) in surface soils from
      Hanoi, Vietnam.

PMID- 17450315
TI  - Chronic cerebellar ataxia and hereditary hemochromatosis: causal or coincidental
      association?

PMID- 17450314
TI  - GSK3beta inhibition and K(ATP) channel opening mediate acute opioid-induced
      cardioprotection at reperfusion.
AB  - Both glycogen synthase kinase 3beta (GSK3beta) and the ATP-dependant potassium
      channel (K(ATP)) mediate opioid-induced cardioprotection (OIC). However, whether
      direct K(ATP) channel openers induce cardioprotection prior to reperfusion and
      their signaling cascade position with respect to GSK3beta inhibition is unknown.
      Therefore, we investigated the role of K(ATP) channel opening at reperfusion in
      OIC, and the interaction between the GSK signaling axis and K(ATP) channels in
      cardioprotection.Male Sprague-Dawley rats underwent 30 minutes ischemia with 2
      hours of reperfusion and infarct size was determined. Rats given the nonselective
      opioid agonist, morphine (0.3 mg/kg), or the selective delta opioid agonist,
      BW373U86 (1.0 mg/kg), 5 minutes prior to reperfusion reduced infarct size (40.3+/
      1.6*, 39.7+/-1.9* versus 60.0+/-1.1%, respectively, * P<0.001%). This protection
      was abrogated with prior administration of the putative sarcolemmal K(ATP)
      antagonist, HMR-1098 (6 mg/kg), or the putative mitochondrial K(ATP) antagonist,
      5-HD (10 mg/kg). The putative sK(ATP) channel opener, P-1075 (1microg/kg) or the
      putative mK(ATP) channel opener, BMS-191095 (1 mg/kg) given 5 minutes prior to
      reperfusion also reduced infarct size (41.8+/-2.4*, 43.4+/-1.4*) and protection
      was abrogated by prior administration of the PI3k inhibitor wortmannin (60.0+/
      1.7, 64.0+/-2.6%, respectively, * P<0.001). Cardioprotection afforded by the GSK
      inhibitor SB216763 (0.6 mg/kg) given 5 minutes prior to reperfusion was also
      partially blocked by either HMR or 5-HD and completely blocked when HMR and 5-HD
      were given in combination (40.8+/-1.6*, 50.4+/-1.6;; 49.4+/-1.7;, 61.6+/-1.6%,
      respectively, * or ; P<0.001). These data indicate that both the sK(ATP) and
      mK(ATP) channel are involved in acute OIC and the GSK signaling axis regulates
      cardioprotection via K(ATP) channel opening.

PMID- 17450316
TI  - Multifocal motor neuropathy with abrupt onset and spontaneous recovery.

PMID- 17450318
TI  - Pure pandysautonomia associated with interferon-alpha therapy.

PMID- 17450317
TI  - Anemia as a risk factor for cerebral venous thrombosis? An old hypothesis
      revisited. Results of a prospective study.
AB  - BACKGROUND: Several case reports have linked iron deficiency anemia with the
      occurrence of cerebral venous thrombosis (CVT) or stroke, yet, it is unclear
      whether this is a chance association. METHODS: In a case-control design data of
      whole blood count and screening for thrombophilic coagulation abnormalities of
      121 prospectively identified patients with CVT and 120 healthy controls were
      compared. Anemia was defined as a hemoglobin (Hb) concentration of <120 g/l in
      females, and <130 g/l in males, severe anemia as a Hb <90 g/l. Adjusted odds
      ratios (OR) were calculated based on a logistic regression model treating
      variables with a level of significance of p < or = 0.2 on univariate analysis as
      potential confounders. RESULTS: Thrombophilia (OR 1.22, 95% CI 1.07-1.76, p <
      0.01), severe anemia (OR 1.10, 95% CI 1.01-2.22, p < 0.05), and
      hypercholesterinemia (OR 1.21, 95% CI 1.04-2.57, p < 0.05) were the only
      independent variables associated with CVT on multivariate analysis. CONCLUSION:
      Severe anemia is significantly and independently associated with CVT.

PMID- 17450319
TI  - The first case of variant Creutzfeldt-Jakob disease in The Netherlands.

PMID- 17450320
TI  - Topographic brain mapping of the international cooperative ataxia rating scale. A
      positron emission tomography study.
AB  - The International Cooperative Ataxia Rating Scale (ICARS) is a 100-point
      semiquantitative scale designed primarily to assess cerebellar dysfunction.
      However, little is known of the metric properties of this scale. We assessed the
      ICARS by rating the severity of cerebellar dysfunction in 27 patients with
      spinocerebellar ataxias (SCA), three patients with sporadic olivopontocerebellar
      ataxia and 24 healthy control subjects. [(18)F]-fluorodeoxyglucose (FDG) positron
      emission tomography (PET) study was also performed on each subject. The
      statistical parametric mapping analyses revealed a significant correlation
      between the ICARS scores and functional impairment of the frontal regions within
      SCA patients. The glucose metabolism in the cerebellum, thalamus and caudate
      nucleus had significant differences between SCA patients and healthy control
      subjects. The results suggested that the clinical severity of SCA patients
      correlated with the functional impairment in the frontal regions, the targets of
      cerebellar efferent projections.

PMID- 17450321
TI  - N-acetyl-L-cysteine as a source of sulfane sulfur in astrocytoma and astrocyte
      cultures: correlations with cell proliferation.
AB  - N-acetyl-L-cysteine (NAC), a precursor of L-cysteine, not only elevates the level
      of glutathione in both astrocytoma and astrocyte cultures, but also affects the
      cellular level of sulfane sulfur. Astrocytoma cells were investigated using the
      stable U373 human cell line. In the U373 cells, N-acetyl-L-cysteine, depending on
      the concentration in the culture medium and culture duration, either elevated or
      diminished the level of sulfane sulfur, and this was respectively accompanied by
      decreased or increased cellular proliferation. In murine astrocytes, in turn, NAC
      was capable of lowering the level of sulfane sulfur and in this way decreased
      cellular proliferation. It seems that normal (astrocyte) and transformed
      (astrocytoma) cells differed in their reaction to NAC in the culture medium. The
      effect of N-acetyl-L-cysteine on astrocytoma cells was advantageous in that it
      inhibited their proliferation through the elevation of the level of sulfane
      sulfur.

PMID- 17450322
TI  - Candida rugosa lipase-catalyzed polyurethane degradation in aqueous medium.
AB  - Candida rugosa lipase (EC 3.1.1.3) was used to degrade commercially-available
      solid poly(ester)urethane (Impranil) in an aqueous medium under different
      temperature, pH, enzyme and substrate concentrations. A mathematical model was
      developed and applied to represent the degradation kinetics of the solid
      polyurethane. Reaction optima were found to be pH 7 and 35 degrees C. Diethylene
      glycol, a degradation byproduct, generation rate was measured to be 0.12 mg/l min
      and the activation energy was calculated as 9.121 kcal/gmol K. This information
      will be useful in developing bioreactors for practical applications to manage
      polyurethane wastes using lipase.

PMID- 17450323
TI  - Complementation of an E. coli cysteine auxotrophic mutant for the structural
      modification study of 3'(2'),5'-bisphosphate nucleotidase.
AB  - The Arabidopsis AHL gene encodes a 3'(2'),5'-bisphosphate nucleotidase (BPNTase)
      involved in the reductive sulfate activation pathway. A bacterial expression
      vector containing AHL cDNA was randomly mutagenized with hydroxylamine and
      transformed into the E. coli cysteine auxotrophic mutant cysQ. Bacterial colonies
      that did not show evidence of complementation, i.e. those that exhibited slower
      growth on cysteine-free medium, were selected for further study. Sequencing of
      the AHL cDNA in one such clone revealed the conversion of cytosine 635 (C635) to
      thymine, resulting in an Alanine (A212) to Valine substitution. This microbial
      complementation procedure is useful in BPNTase structure-activity studies for
      biotechnological applications.

PMID- 17450324
TI  - Electron paramagnetic resonance analyses of biotransformation reactions with
      cytochrome P-450 immobilized on mesoporous molecular sieves.
AB  - Mobil Crystalline Material (MCM-41) can be used for the immobilization of enzymes
      and the investigation of electron transfer in biological systems. Electron
      transfer between MCM-41 with aluminum (Al-MCM-41) and cytochrome P-450 (CYP2B4)
      was observed using electron paramagnetic resonance (EPR). When CYP2B4 was
      immobilized by adsorption, it catalyzed the conversion of aniline to p
      aminophenol. The electron transfer was evidenced when the signal with a g value
      (also called g-factor or spectroscopic manifestation of the magnetic moment) of
      1.98 increased at the same time that the signal with a g value 2.24 decreased due
      to the addition of NADPH to CYP2B4 immobilized on Al-MCM-41, indicating that
      FeIII was reduced to FeII. Therefore, it is possible that Al-MCM-41 participates
      in the electron transfer process in biological systems.

PMID- 17450325
TI  - Activity-based identification of secreted serine proteases of the filamentous
      fungus, Ophiostoma.
AB  - A general activity probe was synthesized and applied to the supernatant of a
      filamentous fungus, Ophiostoma, culture to identify directly the secreted serine
      proteases by covalent enzyme labeling. The activity probe contained a chemically
      reactive group that reacted with, and thus covalently labeled, the serine
      residues of only active proteases and not heat-inactivated proteases. The
      activity probe also contained a fluorescent group that allowed for the subsequent
      visualization of the captured proteases in 1-D gels and their identification by N
      terminal sequencing. This use of a chemical probe led to the rapid discovery of
      subtilisin-like serine protease of Ophiostoma. Two hypothetical proteins were
      also captured, with one being a probable endopeptidase K type of protease.

PMID- 17450326
TI  - Cloning and characterization of a novel Delta12-fatty acid desaturase gene from
      the tree Sapium sebiferum.
AB  - A new full-length cDNA (Ssd12) encoding a Delta12-fatty acid desaturase (Delta12
      FAD) was cloned from Sapium sebiferum using RT-PCR and RACE methods. Ssd12
      contained a 1146 bp open reading frame encoding a protein of 381 amino acids. The
      amino acid sequence showed a much higher match with microsomal Delta12-FAD amino
      acid sequences than chloroplast Delta12-FAD amino acid sequences. Genomic
      Southern blot analysis suggested that Ssd12 had at least two copies. Ssd12
      transcripts were detected in roots, leaves, stems, and seeds by real time PCR.

PMID- 17450327
TI  - Characterization of photosynthetically active duckweed (Wolffia australiana) in
      vitro culture by Respiration Activity Monitoring System (RAMOS).
AB  - The feasibility of oxygen transfer rate (OTR) measurement to non-destructively
      monitor plant propagation and vitality of photosynthetically active plant in
      vitro culture of duckweed (Wolffia australiana, Lemnaceae) was tested using
      Respiration Activity Monitoring System (RAMOS). As a result, OTR proofed to be a
      sensitive indicator for plant vitality. The culture characterization under
      day/night light conditions, however, revealed a complex interaction between
      oxygen production and consumption, rendering OTR measurement an unsuitable tool
      to track plant propagation. However, RAMOS was found to be a useful tool in
      preliminary studies for process development of photosynthetically active plant in
      vitro cultures.

PMID- 17450328
TI  - Emergence of factor IXa as a target for pharmacologic inhibition: editors page.

PMID- 17450329
TI  - Left ventricular lead implantation in an unusual anatomy of the proximal coronary
      sinus.
AB  - A 62-year-old man with Class III heart failure and left bundle branch block
      underwent cardiac resynchronization therapy. Because prior implantation attempts
      from the left side were unsuccessful, the right side approach was attempted.
      However, it was still impossible to advance the pre-shaped sheaths into the
      distal coronary sinus (CS) because the CS was abnormal with a posterior vertical
      take off followed by a sharp sigmoid curve before the AV groove. Ultimately, a
      straight sheath was adjusted to fit the sigmoid curve with the guidance of an
      electrophysiologic catheter and a left ventricular lead was then passed into the
      anterolateral vein.

PMID- 17450330
TI  - Resynchronization therapy in the context of atrial fibrillation: benefits and
      limitations.
AB  - Atrial fibrillation (AF) and heart failure often coexist and are believed to
      directly predispose to each other. Cardiac resynchronization does not prevent or
      increase the induction of AF. However, new onset of AF does not seem to diminish
      the beneficial effects of CRT on symptoms, cardiac function and, more
      importantly, all-cause mortality if appropriate ventricular rate control by beta
      blockers and digoxin is being achieved. While a pharmacological approach to
      control ventricular rate may be sufficient in most patients with paroxysmal AF or
      AF of shorter duration in those with permanent AF ablation strategies may be
      necessary. Observational studies and one randomized trial indicate a potential
      benefit of CRT in heart failure patients with chronic AF; particularly,
      biventricular pacing was superior compared to conventional right-univentricular
      stimulation. However, recent results suggest that even relatively high percentage
      biventricular capture may be inadequate, and that the benefits of CRT may only be
      extended to chronic AF patients with previous AV junctional ablation. Well
      designed and powered clinical trials are required before pacemaker dependency is
      created in large numbers of heart failure patients.

PMID- 17450331
TI  - Postcardiac injury syndrome following radiofrequency ablation of idiopathic left
      ventricular tachycardia.
AB  - A 73-year-old man, who was admitted to our hospital with idiopathic ventricular
      tachycardia, underwent radiofrequency catheter ablation(RFCA) without any
      immediate signs of complications. He complained of sudden onset of chest pain
      shortly after the RFCA procedure. The diagnosis of PCIS was supported by slight
      fever, pericardial effusion, bilateral pleural effusion and elevated inflammatory
      markers. One should be aware of PCIS since there will be increasing performance
      of RFCA procedures and patients may present with this previously rare
      postoperative complications.

PMID- 17450332
TI  - Attenuation values of the intracranial arterial and venous vessels by bolus
      injection of various contrast agents: a study with a single-detector helical CT
      scanner.
AB  - PURPOSE: We evaluated the arteriovenous contrast on the source images of
      intracranial three-dimensional computed tomography (CT) angiography (3D-CTA)
      using a high-concentration (370 mg I/ml) contrast agent in comparison with
      intermediate-concentration (300 mg I/ml) contrast. MATERIALS AND METHODS: With a
      fixed intravenous injection rate and scanning delay, 3D-CTA was performed using a
      single-detector helical CT scanner in 30 consecutive patients. We used 100 ml of
      iohexol 300 for 10 patients, 100 ml of iopamidol 300 for 10 patients, and 80 ml
      of iopamidol 370 for 10 patients. Attenuation values of the bilateral internal
      carotid arteries, bilateral middle cerebral arteries, basilar artery trunk,
      bilateral cavernous sinuses, bilateral basal veins, and Galenic vein were
      measured quantitatively on the axial CT angiographic source images. RESULTS: High
      concentration contrast significantly increased the attenuation values of the
      intracranial arterial system without increasing the attenuation of the venous
      system. CONCLUSION: High-concentration contrast is helpful for obtaining valuable
      arteriovenous contrast on source images with intracranial 3D-CTA.

PMID- 17450333
TI  - Evaluation of tumor blood flow in musculoskeletal lesions: dynamic contrast
      enhanced MR imaging and its possibility when monitoring the response to
      preoperative chemotherapy-work in progress.
AB  - PURPOSE: The objective of this study was to calculate tumor blood flow (TBF) in
      musculoskeletal lesions and to evaluate the usefulness of this parameter in
      differentiating malignant from benign lesions and monitoring the treatment
      response to preoperative chemotherapy. MATERIALS AND METHODS: Altogether, 33
      patients with musculoskeletal lesions underwent a total of 50 dynamic magnetic
      resonance imaging (MRI) examinations, including 28 on 9 patients undergoing
      preoperative chemotherapy. TBF was calculated using deconvolution analysis.
      Steepest slope (SS) was determined from the time-intensity curve during the first
      pass of contrast medium. RESULTS: TBF ranged from 2.7 to 178.6 mL/100 mL/min in
      benign lesions and from 15.4 to 296.3 mL/100 mL/min in malignant lesions. SS
      ranged from 0.5%/s to 31.8%/s for benign lesions and from 3.1%/s to 64.8%/sec for
      malignant lesions. TBF and SS did not differ significantly between benign and
      malignant lesions. Among the nine patients who underwent preoperative
      chemotherapy, TBF after chemotherapy was lower in good responders (11.7, 11.0,
      7.9 mL/100 mL/min) (n = 3, tumor necrosis > or =90%) than in poor responders
      (23.4-141.5 mL/100 mL/min) (n = 6, tumor necrosis <90%). CONCLUSION: TBF and SS
      cannot reliably differentiate malignant from benign lesions. However, they have
      potential utility in evaluating the preoperative treatment response in patients
      with malignant musculoskeletal tumors.

PMID- 17450334
TI  - Enhancement of the liver on dynamic MDCT: investigation among three groups
      consisting of noncirrhotic patients and cirrhotic patients with and without a
      large portosystemic shunt.
AB  - PURPOSE: The aim of this study was to determine any difference in hepatic
      enhancement values on dynamic multidetector row computed tomography (MDCT) among
      three groups: noncirrhotic patients and cirrhotic patients with and without a
      large portosystemic shunt. MATERIALS AND METHODS: A group of 20 noncirrhotic
      patients (group A), 43 cirrhotic patients without a large shunt (group B), and 20
      cirrhotic patients with a large shunt (group C) underwent dynamic MDCT of the
      liver using a standard concentration (300 mg I/ml) and volume (100 ml) of
      contrast material. The attenuation values of the liver were measured during
      arterial, portal, and late phases. RESULTS: The hepatic enhancement value during
      the portal phase was significantly higher in group A (56.2 +/- 13.7 HU) than in
      the other two groups (group B 39.8 +/- 11.9 HU, group C 41.3 +/- 8.3 HU) (P <
      0.01). No significant difference was present between group B and group C. The
      regression line of the scattergram, which shows the relation between the hepatic
      enhancement value during the portal phase and the iodine dose per the patients'
      body weight was more gently sloping in group C than in the other two groups.
      CONCLUSION: In cirrhotic patients without a large shunt, injection of a larger
      amount of total iodine is necessary to optimize hypovascular tumor visualization.
      However, in cirrhotic patients with a large shunt, further investigation is
      needed concerning the effectiveness of administering a larger amount of total
      iodine.

PMID- 17450335
TI  - Multidetector CT findings suggesting a perforation site in the gastrointestinal
      tract: analysis in surgically confirmed 155 patients.
AB  - PURPOSE: The aim of this study was to investigate how accurately we could
      diagnose the level of gastrointestinal (GI) tract perforation using multidetector
      computed tomography (MDCT). MATERIALS AND METHODS: We reviewed 155 patients with
      surgically confirmed GI tract perforation. MDCT scans were obtained with eight
      detector CT; 5 mm thick axial images and 2.5 mm thick coronal multiplanar
      reconstruction (MPR) images were generated for all patients. Contrast enhancement
      was performed in 44 of the 155 patients. Two board-certified radiologists
      reviewed the images for direct findings (free air, ruptured GI tract wall) and
      indirect findings (inflammatory changes, fluid collection, focal thickening of
      the GI tract wall) and attempted to identify the perforation site in each
      patient. RESULTS: Free air was seen in more than 95% of the patients with
      perforation at sites other than the appendix; free air was seen in 44% of
      patients with appendicitis. On contrast-enhanced CT performed in 44 patients,
      rupture of the wall of the GI tract was directly visualized in 14 (32%) on axial
      images only and in 23 (52%) on axial or MPR images, respectively. The perforation
      site was correctly diagnosed in 90% of the patients when the radiologists
      referred to both direct and indirect findings. CONCLUSION: MDCT was valuable for
      identifying the presence and level of GI tract perforation.

PMID- 17450336
TI  - Quantitative assessment of regional left ventricular wall thickness and
      thickening using 16 multidetector-row computed tomography: comparison with cine
      magnetic resonance imaging.
AB  - PURPOSE: The purpose of this study was to investigate the feasibility of
      retrospective electrocardiography-gated multidetector-row computed tomography
      (MDCT) in the assessment left ventricular (LV) wall thickness and thickening and
      to test its validity compared to cine magnetic resonance imaging (MRI) as a
      standard of reference. MATERIALS AND METHODS: We enrolled 19 patients who
      underwent both cardiac MDCT and cine MRI. End-diastolic wall thickness (EDWT) and
      end-systolic wall thickness (ESWT) were measured in 16 myocardial segments.
      Percent systolic wall thickening (%SWT) was generated from the EDWT and ESWT.
      Nondiagnostic myocardial segments were excluded. Correlation and agreement
      between MDCT and cine MRI were analyzed. RESULTS: Segmental assessability values
      were 86.2% (262/304) and 92.1% (280/304) for MDCT and cine MRI, respectively. In
      assessable segments by both modalities (80.9%, 246/304), a significant
      correlation between MDCT and MRI was found (r = 0.89, 0.85, and 0.61, for EDWT,
      ESWT, and %SWT, respectively; all P < 0.05). Mean EDWT and ESWT values by MDCT
      were slightly lower than those by cine MRI (9.8 +/- 3.6 vs. 10.0 +/- 3.7 mm and
      13.8 +/- 4.4 vs. 14.1 +/- 4.3 mm, respectively; both P < 0.01). Bland-Altman
      analysis revealed acceptable limits of agreement between MDCT and Cine MRI.
      CONCLUSION: MDCT is a feasible method to assess regional LV wall thickness and
      systolic thickening.

PMID- 17450337
TI  - Huge uterine leiomyoma with adenomyotic cysts mimicking uterine sarcoma on MR
      imaging.
AB  - Magnetic resonance imaging of a 39-year-old woman who presented with an abdominal
      mass revealed a tumor with hemorrhagic lesions extending from the intrauterine
      space to the subserosa. Hysterectomy was performed for probable uterine sarcoma.
      The histological examination diagnosed uterine leiomyoma with severe myxoid
      degeneration and without malignant components. Hemorrhagic lesions were diagnosed
      as adenomyotic cysts, resulting in findings similar to those of a uterine
      sarcoma.

PMID- 17450338
TI  - Usefulness of FDG PET for diagnosis and radiotherapy of the patient with
      malignant lymphoma involving bone marrow.
AB  - We experienced a case of relapsed malignant lymphoma with multiple bone marrow or
      bone lesions. The case was diagnosed as follicular lymphoma by cytological biopsy
      of the right iliac bone, with (67)Ga scintigraphy showing abnormal, intense
      uptake in multiple bones. After about 10 months of systemic chemotherapy, a
      relapse was suspected because of pain in the bilateral legs and a high level of
      lactate dehydrogenase. Assessment of the lesions in the patient was difficult by
      computed tomography because the affected sites were localized mainly in the bone
      marrow. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was
      useful for detecting accurately the relapse sites in the bone marrow and enabled
      us to determine the field for radiotherapy. There are only a few reports of FDG
      PET findings for such bone marrow malignant lymphomas. Therefore, we report the
      findings of FDG-PET for this case and review some of the literature about bone
      marrow lymphomas.

PMID- 17450339
TI  - Evaluation of the changes in signals from the spleen using ferucarbotran.
AB  - PURPOSE: Because superparamagnetic iron oxide is actively taken into the
      reticuloendothelial system, the signal intensity observed on T2-weighted images
      is reduced not only in the liver but also in the spleen. There is no difference
      in the reduction in signal intensity in the liver after contrast between the
      ferumoxides and ferucarbotran, but the reduction in signal intensity in the
      spleen is considerable. In the present study, we examined the efficacy of T2*
      weighted imaging to compensate for the reduction in signal intensity in the
      spleen by administering ferucarbotran. MATERIALS AND METHODS: We examined the
      images obtained from 35 patients who underwent MRI with ferucarbotran. T2
      weighted images and T2*-weighted images were obtained before and after
      administration of ferucarbotran, and the changes in signal intensity in the liver
      and spleen were then analyzed. RESULTS: A reduction in signal intensity was
      observed in the liver by both T2- and T2*-weighted imaging. In the spleen, the
      signal intensity was reduced on T2-weighted images but was not reduced on T2*
      weighted images. CONCLUSION: The reduction in signal intensity due to
      administration of ferucarbotran is low in the spleen. Thus, it was considered
      necessary to approach the problem of diagnosing ectopic splenic tissue using
      ferucarbotran with caution.

PMID- 17450340
TI  - [Vaccines against herpex simplex virus infections. What's new].

PMID- 17450341
TI  - [Delayed intracutaneous test reaction in heparin intolerance].

PMID- 17450342
TI  - [Treatment of a leg ulcer with bosentan in a female patient with progressive
      systemic scleroderma].

PMID- 17450343
TI  - [HPV-associated carcinoma of the buccal mucosa in a female patient with
      cicatricial mucosal pemphigoid].

PMID- 17450344
TI  - [Neurovascular flaps for the reconstruction of fingertip injuries].
AB  - The fingertip is an extremely specialized end organ with a highly developed sense
      of touch. In this article, we present the different ways of reconstructing a
      traumatized fingertip. Additionally, we systematically explain the differential
      indications for the different techniques available. The whole spectrum of
      fingertip reconstruction is discussed, starting from local neurovascular flaps
      (palmar VY-Atasoy flap, Kutler flap, palmar Moberg flap, lateral Venkataswami and
      Subramanian flap, palmar Hueston flap), distant flaps (Littler flap, Foucher
      flap, dorsal metacarpal artery flap, cross-finger flap, reversed cross-finger
      flap) and finally free flap transfer (free toe-pulp transfer, spare-part
      transplantation). The advantages and disadvantages of each flap are highlighted.
      We develop an algorithm to facilitate finding the correct type of reconstruction.

PMID- 17450346
TI  - [Conservative treatment of aseptic necrosis of the femoral head. Are there
      evidence-based therapy concepts?].
AB  - Osteonecrosis of the femoral head is a locally destructive disease with a
      multifactorial genesis. The majority of patients are men between 35 and 45 years
      of age, who are increasingly reduced in their quality of life and career. As
      these patients are in the middle of their careers, osteonecrosis of the femoral
      head is even of increasing interest for the national economy. It is therefore of
      major interest to reduce the costs as well as the time for its therapy. Since
      conservative treatment is discussed controversially, it was the aim to focus on
      the current literature according to the criteria of evidence-based medicine and
      to prove the importance of conservative treatment of femoral head osteonecrosis.

PMID- 17450347
TI  - [Differential diagnoses of avascular necrosis of the femoral head. Articular
      groin pain in adults].
AB  - Early diagnosis and therapy of hip joint complaints in the young adult are often
      crucial for the prognosis of the joint. Besides avascular necrosis of the femoral
      head several differential diagnoses are possible, which if left untreated
      frequently lead to early osteoarthritis. The necessity of joint replacement in
      middle age often could be avoided by initiating adequate therapy as early as
      possible. The early diagnosis of aseptic necrosis of the femoral head at an early
      stage is possible with MRI. Especially in consideration of decreasing budgets MRI
      is dispensable for other diagnosis, e.g. hip dysplasia, femoroacetabular
      impingement or coxitis. On the other hand para-articular causes and non
      orthopaedic diseases must also be considered, which remain hidden to classic
      orthopaedic diagnostics. Important differential diagnoses of groin pain in the
      adult, with emphasis on articular illnesses, are described.

PMID- 17450348
TI  - [Pathohistology of femoral head necrosis].
AB  - Necrosis of the femoral head represents a special form of aseptic bone necrosis
      because it develops in the high load-bearing region of the hip joint. The
      incidence of the disease is not precisely known. Characteristic macroscopic
      findings include articular cartilage detachment in the load-bearing zone
      immediately below the subchondral osseous lamella, the bordering necrosis of the
      marrow space and bone cells, incursion of the spongiosa, and the gradual loss of
      roundness of the femoral head. The cause of the disease is a disorder in
      circulation supplying the proximal femur. The disease frequently occurs in
      disorders of lipometabolism, after steroid medication, in sickle cell anemia and
      chronic alcoholism, and after fractures of the femoral neck. Histopathological
      classification should distinguish between arthropathy with secondary femoral head
      necrosis and primary forms. Differential diagnosis based on histological findings
      should distinguish between primary coxarthrosis with secondary femoral head
      necrosis, metastases, and a few bone tumors in the epiphyses. Clear cell
      chondrosarcoma is particularly important in the context.

PMID- 17450349
TI  - In memoriam: Ullrich Georg Trendelenburg (31 December 1922-21 November 2006).

PMID- 17450350
TI  - Effects of rosiglitazone on native low-density-lipoprotein-induced respiratory
      burst in circulating monocytes and on the leukocyte-endothelial interaction in
      cholesterol-fed rats.
AB  - Low-density lipoprotein (LDL) has been implicated in the initiation and
      progression of atherosclerotic vascular disease. But whether LDL can elicit
      similar effects in the microcirculation remain unexplored. To approach this
      issue, the hypothesis that LDL promotes oxidative stress in monocytes and results
      in microvascular inflammation was tested. Native LDL was capable of stimulating
      respiratory burst in rat monocytes, and this was blocked by BAPTA, cytochalasin
      B, apocynin, and diphenyliodonium. In monocytes from rats on a high-cholesterol
      (4%) diet, increased intracellular calcium, actin polymerization, respiratory
      burst, and surface CD18 expression were found. Concurrently, leukocyte
      endothelial interaction was enhanced in the cremaster microcirculation.
      Rosiglitazone, an insulin-sensitizing agent with antiinflammatory properties, was
      found to suppress native-LDL-induced actin polymerization and respiratory burst
      in monocytes. It also improved leukocytes activation and leukocyte-endothelial
      interaction due to the high cholesterol intake. Hence, native LDL stimulation of
      monocytes contributed to hypercholesterolemia-associated microvascular
      inflammation, which could be treated by rosiglitazone.

PMID- 17450351
TI  - Cocaine-induced behavioral sensitization in preweanling and adult rats: effects
      of a single drug-environment pairing.
AB  - RATIONALE: Adult rats typically exhibit more robust behavioral sensitization than
      do preweanling rats. A possible explanation for this age-dependent difference is
      that environmental context may have relatively less impact on the psychostimulant
      induced behaviors of preweanling rats. OBJECTIVE: The purpose of this study was
      to assess the importance of environmental context for the development of cocaine
      induced sensitization in preweanling and adult rats. MATERIALS AND METHODS: On
      postnatal day (PD) 19 or PD 79, rats in the context-dependent condition were
      injected with 30 mg/kg cocaine immediately before being placed in a novel test
      chamber for 30 min. The same rats were then injected with saline 30 min after
      being returned to the home cage. Rats in the context-independent condition were
      injected with saline before being placed in the novel chamber and cocaine in the
      home age. Control rats were injected with saline at both time points. One day
      later, adult and preweanling rats were challenged with saline or 10 mg/kg cocaine
      (experiment 1), or preweanling rats were challenged with 5, 20, or 30 mg/kg
      cocaine (experiment 2). After being injected, rats were placed in the test
      chamber, and behavior was measured for 60 min. RESULTS: Adult rats showed context
      dependent locomotor sensitization and conditioned activity, with females
      exhibiting more locomotor activity than males. Preweanling rats did not exhibit
      conditioned activity, but they showed robust context-dependent and context
      independent sensitization when challenged with 10-30 mg/kg cocaine. CONCLUSIONS:
      Context did not influence the expression of behavioral sensitization in
      preweanling rats, suggesting that deficits in associative or memory processes may
      be responsible for age-dependent differences in behavioral sensitization and
      conditioned activity.

PMID- 17450352
TI  - Delayed increase in LDL cholesterol following pentagastrin-induced panic attacks.
AB  - OBJECTIVE: Panic disorder (PD) has been associated with an increased risk for
      cardiovascular (CV) morbidity and mortality. There are inconsistent reports of
      increased low-density lipoprotein cholesterol (LDL-C) in patients with PD.
      Studies have reported a correlation between cholesterol levels and the intensity
      and frequency of panic attacks (PAs), suggesting that an elevation in cholesterol
      could be due to physiological and neurochemical changes that occur during and
      after a PA. The objective of our study was to show that the occurrence of a PA is
      associated with an increase in LDL-C. MATERIALS AND METHODS: We used a double
      blind, placebo-controlled crossover design with randomized injections of placebo
      and pentagastrin in 18 patients with PD (11 men, 7 women) and 33 healthy-control
      subjects (24 men, 9 women). RESULTS: Pentagastrin-induced PAs were associated
      with a statistically significant 10.4% delayed (24 h) increase in LDL-C levels in
      male subjects. Such an effect was not observed in female subjects. CONCLUSION:
      LDL-C levels are directly affected by the occurrence of a PA in males. These
      findings, in association with previous reports of increased cholesterol levels in
      PD patients, suggest that a chronic increase in LDL-C as a result of frequent PAs
      may be one of the mechanisms that contributes, at least in male patients, to
      previously reported increased CV risk in patients with PD. The gender difference
      and the temporal association between PAs and increased LDL-C may explain the
      inconsistency in the findings of previous investigations of cholesterol levels in
      PD patients.

PMID- 17450353
TI  - Differentiation between pediatric spinal arachnoid and epidermoid-dermoid cysts:
      is diffusion-weighted MRI useful?
AB  - BACKGROUND: Appropriate differentiation between epidermoid-dermoid and arachnoid
      cysts is important for patient management. MRI has had limitations in
      differentiating these two types of cysts, especially in the region of the spinal
      cord. OBJECTIVE: To evaluate the role of diffusion-weighted (DW) MRI for
      differentiation between spinal arachnoid and epidermoid-dermoid cysts. MATERIALS
      AND METHODS: Four children underwent conventional and DW MRI. Turbo spin-echo
      imaging was used to obtain DW images. RESULTS: On conventional MRI, low T1-W and
      high T2-W signal was present in all lesions. DW imaging showed restricted
      diffusion in two patients with epidermoid-dermoid cysts and no water restriction
      in two patients with arachnoid cysts. Three of four children had extramedullary
      lesions and one patient had an intramedullary lesion. Three children had surgery,
      two with epidermoid-dermoid cysts and one with arachnoid cyst. Diagnosis was
      confirmed by histopathology. One child with a thoracic arachnoid cyst had stable
      clinical imaging findings during a follow-up of 21 months. CONCLUSION: On
      conventional MRI, epidermoid-dermoid and arachnoid cysts have similar signal
      characteristics. Initial experience with spine DW imaging shows promise in
      differentiating epidermoid-dermoid cysts from arachnoid cysts. Preoperative
      differentiation is important because it changes management and surgical approach.

PMID- 17450354
TI  - Complexity in cattle KIR genes: transcription and genome analysis.
AB  - Killer immunoglobulin (Ig)-like receptors (KIRs) are the major functional natural
      killer (NK) cell receptors in human. The presence of KIR genes has only recently
      been demonstrated in other (non-primate) species, and their expression, genomic
      arrangement, and function in these species have yet to be investigated. In this
      study, we describe the KIR gene family in cattle. KIR sequences were amplified
      from cDNA derived from four animals. Seventeen new sequences were identified in
      total. Some are alleles of two previously described genes, and the remainder are
      representative of at least four additional genes. These cDNA data, together with
      analysis of the cattle genome sequence, confirm that, as in humans, cattle have
      multiple inhibitory and activating KIR genes, with variable haplotype
      composition, and putative framework genes. In contrast to human, the majority of
      the cattle KIR genes encode three Ig-domain KIRs; most of the inhibitory genes
      encode only one immunoreceptor tyrosine-based inhibitory motif (ITIM), and the
      activating genes encode molecules with arginine rather than the more usual lysine
      in the transmembrane domain. A divergent gene, 2DL1, encodes a two Ig-domain KIR
      with an unusual D0-D2 structure, and a distinct signaling domain with two ITIMs.
      Similarity to pig and human two Ig-domain (D0-D2) KIRs suggest these may be more
      related to an ancestral gene than the other cattle KIR genes. Cattle have
      multiple NKG2A-related genes and at least one Ly49 gene; thus, the data presented
      here suggest that they have the potential to express more major
      histocompatibility complex-binding NK receptors than other species.

PMID- 17450355
TI  - The expanded cattle KIR genes are orthologous to the conserved single-copy
      KIR3DX1 gene of primates.
AB  - Cattle are the only non-primate species for which expansion of the killer cell
      immunoglobulin-like receptor (KIR) genes has been reported. We analyzed cattle
      KIR sequences to determine their relationship to the two divergent lineages of
      primate KIR: one comprising the KIR3DX1 gene of unknown function, the second
      comprising all other primate KIR genes, which encode variable major
      histocompatibility complex class I receptors. Phylogenetics and analysis of
      repetitive elements shows that cattle KIR subdivide into the same two lineages as
      primate KIR. Unlike the primates, the lineage of variable and likely functional
      cattle KIR corresponds to the KIR3DX1 lineage of primate KIR, whereas the
      variable lineage of primate KIR is represented in cattle by one KIR gene and a
      related gene fragment.

PMID- 17450356
TI  - Altering the substrate specificity site of Aspergillus niger PhyB shifts the pH
      optimum to pH 3.2.
AB  - Phytases are of biotechnological importance as animal feed additives for their
      ability to catalyze the hydrolysis of phosphate from phytate for absorption by
      simple-stomached animals, and to reduce their fecal phosphorus excretion.
      Aspergillus niger PhyB has high catalytic activity at low pHs around 2.5, but has
      little activity at the commonly observed gastric pH of young animals (3.0-3.5).
      Our objective was to determine if the pH optima of PhyB could be broadened to a
      more characteristic pH range in the stomach of young animals through site
      directed mutagenesis. We created two mutants, E272K and E272Q, each with a single
      amino acid substitution of the same residue in the substrate specificity site.
      Mutants were designed to replace an acidic amino acid, with either a neutral
      amino acid (E272Q) or basic amino acid (E272K), and were overexpressed in the
      yeast Pichia pastoris. While the wild-type (WT) pH optimum was 2.5, mutant E272K
      shifted to a new optimum of pH 3.2. E272K had a concomitant reduction in K (m) of
      36-fold at pH 2.5 and 6-fold at pH 3.2 compared to the WT. Our results indicate
      that the pH optimum of PhyB can be altered to match the stomach pH, along with an
      improved substrate affinity.

PMID- 17450357
TI  - Neuronal imaging using SPECT.
AB  - (123)I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy is one of only a
      few methods available for objective evaluation of cardiac sympathetic function at
      the clinical level. Disorders of cardiac sympathetic function play an important
      role in various heart diseases, and MIBG provides an abundance of useful
      information for the evaluation of severity, prognosis and therapeutic effects;
      this is particularly useful in cases of heart failure, ischaemic heart disease
      and arrhythmic disease. On the other hand, the quantitative indices for MIBG
      differ between institutions, and evidence has not been sufficiently well
      established for MIBG scintigraphy when compared with myocardial perfusion imaging
      in ischaemic heart diseases. In consideration of these difficulties, this review
      provides fundamental information regarding MIBG, its usefulness for various
      diseases and future difficulties.

PMID- 17450358
TI  - The influence of written information during the consenting process on patients'
      recall of operative risks. A prospective randomised study.
AB  - In a recent article, Leigh (J Bone Joint Surg [Br] 88-B:16-18, 2006) notes that
      patients do not lay down memory when being counselled as to the risks involved in
      prospective surgery. In our article we focused on the patients' recall of risk
      factors involved in elective spinal surgery. We assessed the influence of written
      information provided to the patients during the consenting process on their
      recall of operative risks. The study was a prospective randomised study. All
      patients having elective spinal surgery were included in our study from February
      2006 to November 2006 as a consecutive series. Patients were randomised into two
      groups, one of which received routine consent with verbal explanations (group 1),
      the other received the same information supplemented by a written sheet
      explaining the risks of the surgery (group 2). Two weeks later we assessed
      patients' recall of the risk involved in the surgery with a questionnaire and
      compared both groups with a Student t-test. Fifty-three patients (twenty in group
      1 and twenty three in group 2) were involved. We noted a significant difference
      between the two groups in terms of mean number of risks recalled and number of
      patients recalling each risk (p<0.001 and p<0.005, respectively). The addition of
      a written sheet given to patients during the consenting process makes a
      significant difference in terms of their recall of the surgical risks in elective
      lumbar spine surgery. We advocate the routine use of written booklets during the
      consenting process.

PMID- 17450359
TI  - Epidemiology, features and outcome of pain in patients with advanced
      hematological malignancies followed in a home care program: an Italian survey.
AB  - We report on epidemiology, features, outcome, and domiciliary management of pain
      in patients with advanced hematological malignancies followed by an experienced
      hospital-based home care (HC) team. Out of 469 patients, 244 (52%) experienced a
      total of 284 pain syndromes. Pain intensity was rated from mild to moderate in
      31% and from moderate to severe in 69% of them. The diagnosed pain mechanisms
      were deep somatic in 56%, superficial somatic in 15%, visceral 14%, mixed 8%, and
      neuropathic in 7% of pain syndromes, respectively. Incident pain was observed in
      38% of all pain syndromes. In every diagnostic group, deep somatic pain was
      prevalent. Moreover, 85% of visceral pain syndromes were observed in patients
      affected by non-Hodgkin's lymphoma (NHL). In addition, out of 284 pain syndromes,
      150 (51%) were caused by bone involvement. The most frequent recognized pain
      provocative mechanisms were bone marrow expansions, osteolysis, lymph node
      enlargement, and mucositis. In our experience, an approach based on the
      association of causal therapies and analgesics allows optimal control of most
      pain syndromes. Therefore, pain is a major problem in patients affected by
      advanced hematological malignancies, and its management can be effective and
      feasible when carried out by a skilled HC team.

PMID- 17450360
TI  - [Severe Aspergillus endophthalmitis occurring after liver transplantation in an 8
      month-old baby].
AB  - Immunosuppressed patients and transplant patients bear an increased risk for
      invasive aspergillosis and Aspergillus endophthalmitis. An 8-month-old boy
      developed severe unilateral panuveitis after liver transplantation.
      Bronchopulmonary infiltrates were present, but a pulmonary Aspergillus infection
      was not confirmed. An enucleation was performed in order to prevent a life
      threatening disseminated Aspergillus infection.

PMID- 17450362
TI  - Simple technique of head fixation for image-guided neurosurgery in infants.

PMID- 17450364
TI  - Relevance of surgical strategies for the management of paediatric Chiari type I
      malformation.

PMID- 17450365
TI  - Corpus callosotomy using conformal stereotactic radiosurgery.
AB  - OBJECTS: To show the clinical results of a corpus callosotomy (CC) treatment
      using conformal stereotactic radiosurgery (SRS) on a patient with medically
      intractable multifocal epilepsy. MATERIALS AND METHODS: A 17-year-old male
      patient underwent corpus callosotomy conformal SRS using a dedicated linear
      accelerator (linac) with dynamic arcs technique. The prescribed dose was 36.0 Gy
      at the periphery of the rostrum, genu, and a half of the body of the corpus
      callosum (CCA). At 8 months after conformal SRS, the patient developed a
      significant brain edema and moderate transitory motor deficit, which were
      controlled with steroids. After 32 months follow-up, there is an improvement of
      84% on drop attacks and generalized tonic-clonic seizures. CONCLUSIONS: Conformal
      SRS for corpus callosotomy with a single isocenter reproduce the results reported
      on literature using Gamma Knife-based SRS. The results show that this technique
      is safe and demonstrate its efficacy to control seizures.

PMID- 17450367
TI  - Desmoplastic infantile ganglioglioma.

PMID- 17450368
TI  - Prevalence of neural tube defects in economically and socially deprived area of
      China.
AB  - OBJECTIVE: This paper aims to understand the situation and epidemiology trend of
      neural tube defects in Guizhou province, China from 1996 to 2004. STUDY DESIGN:
      Pregnant women from 17 hospitals in Guizhou province were chosen for
      investigation of perinatal infants from January 1996 to December 2004. RESULTS:
      Of 1,208 birth defect cases studied in this 9-year period, a total of 122 cases
      were identified as neural tube defects (NTD), making up a 10.10% of the total
      birth defects. The average prevalence rate of NTD was 12.21 per 10,000 births;
      however, there is no significant difference between the genders. In this study,
      the age of mothers during pregnancy was shown to be one of the major factors
      affecting the prevalence rate of NTD and the differences between infants with or
      without NTD and the usage of folic acid as a supplement during pregnancy were
      found to be statistical significant. CONCLUSION: NTD was found to be the most
      common and serious form of human birth defect in Guizhou province. For
      prevention, folic acid supplement is thought to be efficacious in inhibiting NTD,
      and thus, it is essential for people in socially deprived areas to effectively
      reduce the prevalence of NTD in China.

PMID- 17450369
TI  - Incidence of vascular malformations in spontaneous intra-cerebral haemorrhage in
      children.
AB  - AIM: To assess the incidence of vascular malformations in children presenting
      with non-traumatic intra-cerebral haemorrhage and outline the need for
      radiological investigations. MATERIALS AND METHODS: Between 1993 and 2002, 26
      children presented with spontaneous intra-cerebral haemorrhage at a mean age of
      26 months (range 1-192 months). RESULTS: Twenty-two children had, as first
      treatment, surgical removal of the haematoma and any malformation found. One
      patient with no evidence of vascular malformation had conservative treatment, two
      had embolisation and one had stereotactic radiosurgery of arteriovenous
      malformations (AVMs). The diagnosis of vascular malformation was confirmed
      histologically and/or radiologically in 16 (61%) patients. Of these 16 patients,
      7 were AVMs, 1 thrombosed middle cerebral artery (MCA) aneurysm, 1 cavernous
      angioma, 6 aggregates of abnormal vessels, 1 vein of Galen aneurysm. Pre
      operatively, 12 patients had magnetic resonance imaging (MRI)/magnetic resonance
      angiography (MRA) and 7 were positive for vascular malformation (1 false
      positive) with no false negatives. Digital subtraction angiography (DSA) was
      performed pre-operatively in 7 patients, 4 were positive with no false negatives.
      There were no re-bleeds at the follow-up period. Five (19%) patients died from
      the haemorrhage, 7 (27%) had severe neurological deficit and 14 (54%) had no
      neurological deficit. Residual malformation after surgery requiring additional
      treatment was found in 3 (16%) patients. All patients with confirmed
      malformations were followed-up with DSA. CONCLUSION: MRI/MRA has high sensitivity
      and specificity in identifying vascular malformations in children presenting
      acutely with spontaneous intra-cerebral haemorrhage. This may prove useful when
      pre-operative DSA is not promptly available. After acute clot evacuation, there
      is high incidence of residual malformation and such patients should be followed
      up with DSA.

PMID- 17450370
TI  - Four-part fracture after intrathoracic displacement of the humeral head: a case
      report and review of the literature.
AB  - Displaced four-part fracture dislocation represents the highest risk of
      osteonecrosis of the humeral head due to a disruption of the blood supply. In a
      few cases, that dislocation can be intrathoracic which worsens prognosis with
      life-threatening injuries such as hemothorax or pneumothorax. This paper presents
      the case of a 77-year-old woman after having fallen down the stairs with an
      intrathoracic dislocation four-part fracture leaving the head in the thorax. We
      analyze mechanisms and review the literature in order to highlight this lesion
      and provide a take home message for the treatment.

PMID- 17450371
TI  - Infiltration of the pes anserinus complex by an extraarticular diffuse-type giant
      cell tumor (D-TGCT).
AB  - This report describes the case of a 26-year-old woman with a recurrent
      extraarticular diffuse-type tenosynovial giant cell tumor (D-TGCT) of the medial
      region of the knee affecting the pes anserinus and hamstring tendons. Presurgical
      MRI did not exclude infiltrative properties of the tumor. In the histological
      evaluation, the tumor showed an aggressive dispersion by infiltrating the
      collagenous tissue of the hamstring tendons. The treatment included a resection
      of the pes anserinus complex with distal semitendinosus and gracilis tendons.
      Regarding extraarticular D-TGCT a review of the literature showed a predominant
      affection of the medial region of the knee and thigh.

PMID- 17450372
TI  - Extracellular bicarbonate and non-bicarbonate buffering against lactic acid
      during and after exercise.
AB  - Defense of extracellular pH constancy against lactic acidosis can be estimated
      from changes (Delta) in lactic acid ([La]), [HCO(3)(-)], pH and PCO(2) in blood
      plasma because it is equilibrated with the interstitial fluid. These quantities
      were measured in earlobe blood during and after incremental bicycle exercise in
      13 untrained (UT) and 21 endurance-trained (TR) males to find out if acute and
      chronic exercise influence the defense. During exercise the capacity of non
      bicarbonate buffers (beta(nbi) = -Delta[La] . DeltapH(-1) - Delta[HCO(3)(-)] .
      DeltapH(-1)) available for the extracellular fluid (mainly hemoglobin, dissolved
      proteins and phosphates) amounted to 32 +/- 2(SEM) and 20 +/- 2 mmol l(-1) in UT
      and TR, respectively (P < 0.02). During recovery beta(nbi) decreased to 14 (UT)
      and 12(TR) mmol l(-1) (both P < 0.001) corresponding to values previously found
      at rest by in vivo CO(2) titration. Bicarbonate buffering (beta(bi)) amounted to
      44-48 mmol l(-1) during and after exercise. The large exercise beta(nbi) seems to
      be mainly caused by an increasing concentration of all buffers due to shrinking
      of the extracellular volume, exchange of small amounts of HCO(3)(-) or H(+) with
      cells and delayed HCO(3)(-) equilibration between plasma and interstitial fluid.
      Increase of [HCO(3)(-)] during titration by these mechanisms augments total beta
      and thus the calculated beta(nbi) more than beta(bi) because it reduces DeltapH
      and Delta[HCO(3)(-)] at constant Delta[La]. The smaller rise in exercise
      beta(nbi) in TR than UT may be caused by an increased extracellular volume and an
      improved exchange of La(-), HCO(3)(-) and H(+) between trained muscles and blood.

PMID- 17450375
TI  - Increase in XET activity in bean (Phaseolus vulgaris L.) cells habituated to
      dichlobenil.
AB  - Bean (Phaseolus vulgaris L.) cells have been habituated to grow in lethal
      concentrations of dichlobenil (DCB), a specific inhibitor of cellulose
      biosynthesis. Bean callus cells were successively cultured in increasing DCB
      concentrations up to 2 microM. The 2-microM DCB habituated cells were
      impoverished in cellulose and xyloglucan, had an increased xyloglucan
      endotransglucosylase (XET; EC 2.4.1.207) activity, together with an increased
      growth rate and a decreased molecular size of xyloglucan. However, the
      application of lethal concentrations of two different cellulose-biosynthesis
      inhibitors (DCB and isoxaben) for a short period of time produced little effect
      on XET activity and xyloglucan molecular size. We propose that the weakening of
      plant cell wall provoked by decrease in cellulose content might promote the
      xyloglucan tethers and increase the ability of xyloglucan to bind to cellulose in
      order to give rigidity to the wall.

PMID- 17450373
TI  - Current concepts and perspectives of immunosuppression in organ transplantation.
AB  - BACKGROUND: While early surgical success made organ transplantation possible in
      the 1950s and 1960s, the breakthrough in clinical organ transplantation was
      achieved through the discovery and invention of modern immunosuppressive agents
      in the early/mid-1980s. Especially during the 1990 s, a large array of
      immunosuppressants has expanded the armamentarium used to prevent and treat
      allograft rejection, resulting in an excellent short-term and an acceptable long
      term outcome. However, these drugs have potent but still non-specific
      immunosuppressive properties and frequently show severe acute and chronic side
      effects, sometimes questioning the overall success. CONCEPTS/TRENDS: As the "Holy
      Grail" of the transplant community, the induction of "true donor-specific
      tolerance" has not been achieved yet; current immunosuppressive strategies, in
      particular in Europe, include "individually tailored immunosuppressive"
      protocols, mostly based on specific immunologic and non-immunologic risk factors.
      These protocols allow for optimal immunosuppressive protocols for each patient
      group according to their needs by choosing the most suitable, well-tolerated
      combination of agents and the most effective doses to avoid acute rejection
      episodes (incidence and severity) and minimise drug-related toxicity to reduce
      long-term drug-related morbidity and mortality. Nevertheless, transplant
      recipient are still being forced to take a life-long course of chemical
      immunosuppressive agents to keep their graft, knowing about the possible life
      threatening side effects. SUMMARY: We review current trends of immunosuppressive
      protocols in liver and kidney transplantation, focusing on calcineurin-inhibitor
      sparing protocols, mammalian-target-of-rapamycin (mTOR) inhibitor based-protocols
      and corticosteroid-avoidance protocols, being aware of the fact, that most of
      these strategies could be applicable for other transplanted organs, too. Finally,
      we describe future trends and new developments that are rising on the horizon.

PMID- 17450377
TI  - Cloning and developmental expression of the Xenopus Nkx6 genes.
AB  - The evolutionarily conserved Nkx6 family transcription factors play important
      roles in the patterning of the central nervous system (CNS) and pancreas in
      vertebrates. In this study, we describe the cloning and expression patterns of
      the three Nkx6 family genes in Xenopus laevis. Like their mouse and chicken
      homologues, Xenopus Nkx6 family genes are mainly expressed in the CNS and
      anterior endodermal tissues during embryonic development. Nkx6.1 and Nkx6.2 share
      overlapping expression domains in the ventral neural tube at neurula stages and
      later in the ventral part of developing hindbrain and spinal cord. Nkx6.3 is
      detected in the non-neural ectoderm from cleavage to early neurula stages and in
      the caudal hindbrain and the mandibular arch at tail bud stages. In the endoderm,
      Nkx6.2 is expressed in the hypochord at tail bud stages. At tadpole stages, the
      three Nkx6 genes are differentially expressed in the anterior endoderm
      derivatives, including the pancreas, stomach, esophagus, and lung.

PMID- 17450376
TI  - Characterisation of a prokaryote-type tRNA-isopentenyltransferase gene from the
      moss Physcomitrella patens.
AB  - Cytokinins are of critical importance to numerous developmental processes in
      plants. Two cytokinin biosynthetic pathways have been described; each one uses a
      different type of isopentenyltransferases (IPTs) as the key enzyme. In the first
      pathway, adenylate-IPTs (EC 2.5.1.27) prenylate adenylic nucleotides to cytokinin
      nucleotides, thus catalysing the direct de novo biosynthesis of free cytokinins.
      In the second pathway, tRNA-IPTs (EC 2.5.1.8) catalyse cytokinin formation by
      isopentenylation of tRNA, the degradation of which liberates cytokinin
      nucleotides. Seed plants have been shown to possess both forms of IPTs. Here, we
      report on the in-silico based identification and on the functional
      characterisation of an IPT encoding gene (PpIPT1) from the bryophyte
      Physcomitrella patens. Analysis of the PpIPT1 amino acid sequence revealed high
      similarities to tRNA-IPTs of other plants. No adenylate-IPT genes were found in
      the Physcomitrella sequenced transcriptome/genome. PpIPT1 functionally
      complemented a defective tRNA-IPT gene of Saccharomyces cerevisiae (ScMOD5) in
      the strain MT-8. Dephosphorylated tRNA hydrolysates from PpIPT1-transformed MT-8
      showed cytokinin activity in a moss bioassay and the presence of
      isopentenyladenosine in HPLC analysis, in contrast to those prepared from
      untransformed MT-8. A comparison of pro- and eukaryotic homologues revealed two
      classes of tRNA-IPTs; PpIPT1 belongs to a prokaryotic type with predicted
      chloroplast targeting. RT-PCR experiments revealed a stronger expression in the
      cytokinin overproducing mutant oveST25, thus indicating the potential role of
      PpIPT1 for cytokinin biosynthesis in the evolutionary old land plant
      Physcomitrella.

PMID- 17450378
TI  - Pulmonary vascular changes in piglets with increased pulmonary blood flow and
      pressure.
AB  - In this model of pulmonary vascular disease, high pulmonary blood flow was
      created by an anastomosis between the left subclavian artery and the main
      pulmonary artery [Blalock-Taussig (BT) shunt] in 4-week-old piglets (n = 6).
      Additional ligation of the left pulmonary artery (LPA) was used to increase
      pulmonary artery pressure (n = 6). Seven piglets were sham-operated. After 3
      months, mean pulmonary artery pressure was higher in animals with BT shunt and
      LPA ligation (22 +/- 5; mean+/-SD) compared to sham-operated animals (15 +/- 2).
      In addition, thickening of the medial coat (20.1 +/- 2.8% versus 13.6 +/- 3.1%
      wall thickness) and increased immunostaining for vascular endothelial growth
      factor A (VEGF-A) were observed. Relative gene expression for endothelin
      converting enzyme-1 (ECE-1) mRNA was 1.8 times higher, and VEGF-A mRNA was 2.5
      times higher in pigs with BT shunt and LPA ligation compared with sham-operated
      animals. VEGF receptor-1 and VEGF receptor-2 mRNA was lower in shunted animals
      and in animals with additional ligation of LPA. Upregulation of ECE-1 and VEGF-A,
      as well as changes in VEGFR expression in the pulmonary hypertensive lung, may
      contribute to pulmonary vascular changes.

PMID- 17450379
TI  - Serrated polyps of the colorectum: is sessile serrated adenoma distinguishable
      from hyperplastic polyp in a daily practice?
AB  - The distinction between serrated polyps of the colon is complex, particularly
      between hyperplastic polyps (HP) and sessile serrated adenomas (SSA). Recent data
      show that SSA might be the precursors of serrated colonic cancers, underlining
      the necessity of identifying them. We characterized the demographic and
      pathologic characteristics of 102 serrated lesions among 321 polyps of the
      colorectum and determined if SSA can be microscopically distinguished from HP in
      biopsy material of a daily practice. There were 81 HP (79%) and 7 SSA (7%) of
      which one displayed low-grade dysplasia. Only six serrated polyps (6%) could not
      be correctly classified. The main architectural criteria for distinguishing SSA
      from HP is the serrated feature along the crypt axis and the rarity of
      undifferentiated cells in the lower third of the crypts. SSA was significantly
      more often located in the right colon and larger (median, 11 vs 4 mm) than HP.
      SSA are rare serrated polyps that can be distinguished from HP based on their
      morphology, location in the right colon, and larger size. One SSA of our series
      showed low-grade dysplasia supporting the concept that this lesion might be a
      precursor of serrated adenocarcinoma.

PMID- 17450380
TI  - A novel method to investigate pemphigus-induced keratinocyte dysmorphisms through
      living cell immunofluorescence microscopy.
AB  - Pemphigus vulgaris (PV) blistering occurs as a result of the disruption of
      intercellular contacts among keratinocytes, or acantholysis. The hallmark of PV
      acantholysis in vitro is considered to be the retraction of keratin intermediate
      filaments (KIF) onto the nucleus, which parallels with loss of cell-cell adhesion
      and rounding up of keratinocytes. However, the fine morphological changes of
      keratinocytes as well as the fate of cell adhesion structures cannot be
      appreciated on immunofluorescence by the simple cytokeratin staining. In this
      paper, we show that acantholytic dysmorphisms are sharply investigated by using
      PV IgG as a primary antibody on metabolically quiescent living cells. Indeed, PV
      IgG recognise a wide spectrum of molecules and enabled us to monitor the main
      changes occurring in acantholytic keratinocytes, including cell shrinkage with
      the appearance of prickle-like processes, detachment of keratinocytes from one
      another and collapse of cytoskeleton-bound proteins along nuclear periphery. This
      method has wider applications as it could be useful for staining cell periphery
      of keratinocytes and changes in cell shape. Furthermore, images displayed clear
      and sharp contours because living cell microscopy allows to avoid antigen
      distortion due to cell manipulation, which usually precedes the immunolabelling.

PMID- 17450381
TI  - Unilateral pulmonary edema and acute rheumatic fever.
AB  - Although the diagnostic criteria for acute rheumatic fever (ARF) are well known,
      a high index of suspicion is necessary in order to assure timely diagnosis and
      appropriate treatment. We present a case of an 8-year-old child who presented
      with unilateral pulmonary edema secondary to acute mitral insufficiency due to
      ARF. ARF should be considered in the differential diagnosis of unilateral
      pulmonary edema in children.

PMID- 17450382
TI  - Inhibition of connexin 43 expression and function in cultured rat dental pulp
      cells by antisense oligonucleotide.
AB  - Connexins are gap-junction proteins forming hexameric structures in the plasma
      membranes of adjacent cells, thereby creating intercellular channels. Connexin 43
      (CX43) is expressed in pulp tissue. However, its function in dental pulp tissue
      has yet to be fully investigated. We have employed antisense oligonucleotides
      (AS) against rat CX43 to study the role of CX43 in dental pulp cells. Cultured
      dental pulp cells were treated with AS or sense (S) oligonucleotides. The number
      of cells in the AS-treated groups was approximately 1.3-fold that in the S
      treated controls. Growth rates were significantly different between the AS- and S
      treated groups at 48 h (P < 0.01). An alkaline phosphatase assay revealed that AS
      treated pulp cells dramatically decreased at 48 h after AS incorporation, whereas
      S-treated pulp cells showed no marked changes. Western blot analysis revealed
      that heat-shock protein 25 was highly expressed in S-treated cells but was only
      weakly expressed in AS-treated cells at 48 h. Furthermore, AS-treated cells
      highly expressed CX45, whereas S-treated cells exhibited high expression of CX32.
      These results suggest that CX43 is involved in cell growth, mineralization, and
      differentiation to odontoblasts in rat pulp cells, and that CX43 plays the
      opposite role to that of CX45.

PMID- 17450383
TI  - Molecular characterization and cell-specific expression of an ion transport
      peptide in the tobacco hornworm, Manduca sexta.
AB  - The crustacean hyperglycemic hormone (CHH) peptides regulate diverse
      physiological processes from reproduction to metabolism and molting in
      arthropods. In insects, the ion transport peptides (ITP), also members of the CHH
      family, have only been implicated in ion transport. In this study, we sequenced a
      nucleotide fragment spanning the conserved A1/A2 region of the putative CHH/ITP
      gene. This fragment was amplified from larval cDNA of the tobacco hornworm,
      Manduca sexta and showed a high degree of sequence conservation with the same
      region from other insects and, to a lesser degree, with that of crustacean
      species, suggesting the presence of a Manduca-specific CHH/ITP mRNA (MasITP
      mRNA). CHH-like immunocytochemical analyses with two crustacean antisera (from
      Carcinus maenas and Cancer pagurus) identified the presence of CHH-like
      immunoreactivity in nervous tissue of all developmental stages, but not in the
      gut of M. sexta. Specifically, CHH-like peptides localized to paired type IA(2)
      neurosecretory cells of the pars lateralis of the brain (projecting
      ipsilaterallly to the corpora cardiaca-allata complex) and to neurosecretory
      cells and transverse nerves of the ventral nerve cord in larvae, pupae, and
      adults. The distribution of the putative MasITP peptide shifted during
      development in a manner consistent with metamorphic reorganization. A comparison
      of hemolymph equivalents of CHH detected by enzyme-linked immunosorbent assay
      with CHH-like immunoreactivity in transverse nerves provided evidence for the
      release of MasITP from the transverse nerves into the hemolymph at insect
      ecdysis. These data suggest the presence of an insect ITP in M. sexta and a role
      for this hormone during ecdysis.

PMID- 17450384
TI  - Involvement of signaling of VEGF and TGF-beta in differentiation of sinusoidal
      endothelial cells during culture of fetal rat liver cells.
AB  - Embryonic development of the liver is closely associated with vascular
      organization. However, little is known about the mechanisms of vascular
      differentiation during liver development. Our previous study showed that the
      maturation of sinusoidal endothelial cells (SECs) occurred during embryonic day
      13.0 (E13.0) to E15.0. To improve our understanding of SEC differentiation, we
      examined here the expression of maturation markers, SE-1 and stabilin-2, in fetal
      livers and also attempted to establish an in vitro SEC differentiation system by
      culturing E13.5 fetal liver cells. Immunohistochemical examination of SE-1 and
      stabilin-2 expression during fetal rat liver development revealed that these
      differentiation markers were co-expressed in SECs in the late stage of liver
      development, although stabilin-2 was expressed in almost all vascular endothelial
      cells in the early stage. Liver cells from the E13.5 rat fetus were cultured in
      EBM-2 medium containing vascular endothelial growth factor (VEGF), transforming
      growth factor beta1 (TGF-beta1) and VEGF plus SB-431542 (an inhibitor of the TGF
      beta1 receptor, activin receptor-like kinase 5 [ALK-5]). In vitro SEC
      differentiation, as indicated by the appearance of cells co-expressing SE-1 and
      stabilin-2 and of cells with cytoplasmic fenestrae in endothelial sheets, was
      induced by the addition of both VEGF and SB-431542, an inhibitor of the
      phosphorylation of Smad2/3 but not that of Smad1/5/8 in the cultured cells. These
      results indicate for the first time that both VEGF signaling and the blocking of
      the ALK-5-Smad2/3 signal pathway are important for the fetal differentiation of
      SECs.

PMID- 17450385
TI  - Rhabdomyolysis and acute renal failure in a child with para-influenza type 1
      infection.
AB  - We present a rare case of para-influenza type 1 virus-induced rhabdomyolysis,
      complicated by acute renal failure (ARF). The child underwent continuous
      venovenous haemofiltration and has shown full clinical and biochemical recovery.
      ARF due to rhabdomyolysis in para-influenza type 1 infection in a child has, to
      the best of our knowledge, not been previously reported.

PMID- 17450386
TI  - Expression profiles of congenital renal dysplasia reveal new insights into renal
      development and disease.
AB  - Congenital renal dysplasia (RD) is a major cause of renal failure in the
      pediatric population. Although molecular and genetic aspects of RD have been
      studied in animal models, limited studies have been done in human RD primarily
      due to lack of available material. To identify novel genes that are associated
      with RD and normal kidney development, we performed microarray analysis on total
      RNA extracted from age-matched fetal kidneys of normal and RD patients. In
      midgestational RD kidneys, we found 180 upregulated and 104 downregulated
      transcripts compared with normal kidneys. Among the increased transcripts in the
      dysplastic kidneys were matrix-degrading enzymes (MMP7, MMP19, TIMP1),
      inflammation- and immunity-related genes, and growth factors. Expression of genes
      known to be essential for normal kidney development, such as WT1, BMP7, renin,
      angiotensin receptor 2 (AGTR2), SAL-like 1 (SALL1) and glypican 3 (GPC3), were
      decreased in dysplastic kidneys. Expression of selected gene products (BMP7,
      renin, and MMP7) was further confirmed in parallel sections and in several normal
      and human dysplastic kidneys, supporting the role of these genes as putative RD
      biomarkers. These results are among the first to reveal disrupted expression
      profiles during gestation in human RD patients.

PMID- 17450387
TI  - The associations between living conditions, demography, and the 'impact of
      cancer' scale in tumor-free cancer survivors: a NOCWO study.
AB  - GOALS OF WORK: The "impact of cancer" scale (IOC) is a new questionnaire that
      explores attitudes in the physical, psychological, social, and
      spiritual/existential domains in cancer survivors. This study explores the
      associations between demography, living conditions (LCs), and the IOC dimensions
      in disease-free Norwegian survivors who have been treated for breast, prostate,
      or testicular cancer. MATERIALS AND METHODS: A questionnaire covering demography,
      LCs, and the IOC was mailed to 852 cancer survivors; 459 (54%) participated. A
      living condition index (LCI) was calculated based on self-reported education,
      employment, annual income, health, housing expenditures, and social
      participation. MAIN RESULTS: Survivors with a low LCI level viewed their
      situation significantly worse on four of five negative IOC dimensions than those
      with high LCI level. No significant LCI-related differences were observed for the
      mean scores of positive IOC dimensions. Significant associations were observed
      between gender, health status, employment, and five to six IOC dimensions. LCs
      were more often associated with the negative IOC dimensions than the positive
      ones. CONCLUSIONS: The significant associations between LCs and dimensions of the
      IOC in tumor-free cancer survivors show that LCs should be considered when health
      care professionals assist cancer survivors in dealing with the impact the cancer
      experience had on their lives.

PMID- 17450388
TI  - CT pitfalls in emergency radiology: a chronically ruptured intra-cranial dermoid
      tumor mimicking pneumocephalus in an acute multi-trauma evaluation.
AB  - Traumatic rupture of an intracranial dermoid tumor is an unusual event. In this
      case, however, a ruptured intracranial dermoid is noted, but in the absence of
      clinical signs and symptoms. The lack of symptoms coupled with an abnormal
      cerebral computed tomography (CT) initially created confusion among clinicians
      until a more detailed history and more careful analysis of the head CT revealed
      the plausible answer.

PMID- 17450389
TI  - Enhanced T-ray signal classification using wavelet preprocessing.
AB  - This study demonstrates the application of one-dimensional discrete wavelet
      transforms in the classification of T-ray pulsed signals. Fast Fourier transforms
      (FFTs) are used as a feature extraction tool and a Mahalanobis distance
      classifier is employed for classification. Soft threshold wavelet shrinkage de
      noising is used and plays an important role in de-noising and reconstruction of T
      ray pulsed signals. An iterative algorithm is applied to obtain three optimal
      frequency components and to achieve preferred classification performance.

PMID- 17450390
TI  - Effects of Accreditation Council for Graduate Medical Education work hour
      restrictions on medical student experience.
AB  - BACKGROUND: Residents have a major role in teaching students, yet little has been
      written about the effects of resident work hour restrictions on medical student
      education. OBJECTIVE: Our objective was to determine the effects of resident work
      hour restrictions on medical student education. DESIGN: We compared student
      responses pre work hour restrictions with those completed post work hour
      restrictions. PARTICIPANTS: Students on required Internal Medicine, Surgery, and
      Pediatric clerkships at the University of Minnesota. MEASUREMENTS: Two thousand
      eight hundred twenty-five student responses on end-of-clerkship surveys. RESULTS:
      Students reported 1.6 more hours per week of teaching by residents (95%CI 0.8
      2.6) in the post work hours era. Students' ratings of the overall quality of
      their teaching on the ward did not change appreciably, 0.05 points' decline on a
      5-point scale (P = .05). Like the residents, students worked fewer hours per week
      (avg. 1.5 hours less, 95%CI 0.4-2.6). There was no change in quality or quantity
      of attending teaching, students' relationships with their patients, or the
      overall value of the clerkships. CONCLUSIONS: Whereas resident duty hour
      restrictions at our institution have had minimal effect on students' ratings of
      the overall teaching quality, they do report being taught more by their
      residents. This may be a factor of decreased resident fatigue or an increased
      sense of well-being; but more study is needed to clarify the causes of our
      observations.

PMID- 17450391
TI  - The simultaneous occurrence of deep vein thrombosis and pulmonary and arterial
      embolization.
AB  - INTRODUCTION: A 45-year-old female presented with 8 hours of right lower
      extremity pain and dyspnea. She was tachycardic and her right lower extremity was
      dusky, cold, and pulseless. DISCUSSION: Computerized tomography of the venous and
      arterial systems revealed massive pulmonary embolism and right lower extremity
      arterial and left lower extremity venous thromboses. Management included intra
      arterial thrombolytics, right lower extremity arterial embolectomy, and
      anticoagulation. Echocardiogram revealed a patent foramen ovale (PFO) with a
      right-to-left shunt. CONCLUSION: We hypothesize that our patient developed deep
      venous thrombosis that led to major pulmonary embolization and increased right
      sided pressures. In the setting of a patent foramen ovale, a later venous embolus
      transversed the PFO and lodged in the femoral artery. Our case illustrates the
      importance of a high index of suspicion for a paradoxical embolus in patients
      with arterial thrombosis.

PMID- 17450392
TI  - Isolation and characterization of diuron-degrading bacteria from lotic surface
      water.
AB  - The bacterial community structure of a diuron-degrading enrichment culture from
      lotic surface water samples was analyzed and the diuron-degrading strains were
      selected using a series of techniques combining temporal temperature gradient gel
      electrophoresis (TTGE) of 16 S rDNA gene V1-V3 variable regions, isolation of
      strains on agar plates, colony hybridization methods, and biodegradation assays.
      The TTGE fingerprints revealed that diuron had a strong impact on bacterial
      community structure and highlighted both diuron-sensitive and diuron-adapted
      bacterial strains. Two bacterial strains, designated IB78 and IB93 and identified
      as belonging to Pseudomonas sp. and Stenotrophomonas sp., were isolated and shown
      to degrade diuron in pure resting cells in a first-order kinetic reaction during
      the first 24 h of incubation with no 3,4-DCA detected. The percentages of
      degradation varied from 25% to 60% for IB78 and 20% to 65% for IB93 and for a
      diuron concentration range from 20 mg/L to 2 mg/L, respectively. It is
      interesting to note that diuron was less degraded by single isolates than by
      mixed resting cells, thereby underlining a cumulative effect between these two
      strains. To the best of our knowledge, this is the first report of diuron
      degrading strains isolated from lotic surface water.

PMID- 17450393
TI  - Nitrogen fixation in microbial mat and stromatolite communities from Cuatro
      Cienegas, Mexico.
AB  - Nitrogen fixation (nitrogenase activity, NA) of a microbial mat and a living
      stromatolite from Cuatro Cienegas, Mexico, was examined over spring, summer, and
      winter of 2004. The goal of the study was to characterize the diazotrophic
      community through molecular analysis of the nifH gene and using inhibitors of
      sulfate reduction and oxygenic and anoxygenic photosynthesis. We also evaluated
      the role of ultraviolet radiation on the diazotrophic activity of the microbial
      communities. Both microbial communities showed patterns of NA with maximum rates
      during the day that decreased significantly with 3-3,4-dichlorophenyl-1',1'
      dimethylurea, suggesting the potential importance of heterocystous cyanobacteria.
      There is also evidence of NA by sulfur-reducing bacteria in both microbial
      communities suggested by the negative effect exerted by the addition of sodium
      molybdate. Elimination of infrared and ultraviolet radiation had no effect on NA.
      Both microbial communities had nifH sequences that related to group I, including
      cyanobacteria and purple sulfur and nonsulfur bacteria, as well as group II
      nitrogenases, including sulfur reducing and green sulfur bacteria.

PMID- 17450394
TI  - Changes in fungal community composition in response to vegetational succession
      during the natural regeneration of cutover peatlands.
AB  - Despite the importance of peatlands as a major store of sequestered carbon and
      the role of fungi in releasing sequestered C, we know little about the community
      structure of fungi in peatlands. We investigated these across a gradient of
      naturally regenerating peatland vegetation using denaturing gradient gel
      electrophoresis (DGGE) and clone libraries of fragments of the fungal rRNA
      internal transcribed spacer (ITS) region. Significant changes in the fungal
      community structure of peat samples at different stages of regeneration were
      observed, which relate to the composition of the vegetation recolonizing these
      sites. Cloning and sequence analysis also demonstrated a potential shift in the
      relative abundance of the main fungal phyla. Some of the clones identified to
      genus level were highly related to fungi known to play a role in the degradation
      of plant litter or wood in similar ecosystems and/or form mycorrhizal
      associations. In addition, several fungal isolates highly related to peat clones
      were obtained, and their enzymic capacity to degrade structural plant tissues was
      assessed. Together, these results suggest that the fungal community composition
      of peat may be an important indicator of the status of regeneration and potential
      carbon sequestration of cutover peatlands.

PMID- 17450397
TI  - Endovascular repair of a type III thoracoabdominal aortic aneurysm in a patient
      with occlusion of visceral arteries.
AB  - The successful endovascular repair of a type III thoracoabdominal aortic aneurysm
      (TAAA) with the use of a tube endograft is reported. A 56-year-old male with a
      6.4-cm type III TAAA, a 4.2-cm infrarenal abdominal aortic aneurysm, and chronic
      renal insufficiency presented with flank pain, nausea, acute anuria, and serum
      creatinine of 6.1 mg/dl. Acute occlusion of the left solitary renal artery was
      diagnosed and emergent recanalization with percutaneous transluminal angioplasty
      and stenting was performed successfully, with reversal of the serum creatinine
      level at 1.6 mg/dl. Further imaging studies for TAAA management revealed ostial
      occlusion of both the celiac artery (CA) and the superior mesenteric artery (SMA)
      but a hypertrophic inferior mesenteric artery (IMA) providing retrograde flow to
      the aforementioned vessels. This rare anatomic serendipity allowed us to repair
      the TAAA simply by using a two-component tube endograft without fenestrations
      (Zenith; William Cook, Bjaeverskov, Denmark) that covered the entire length of
      the aneurysm, including the CA and SMA origins, since a natural arterial bypass
      from the IMA to the CA and SMA already existed, affording protection from
      gastrointestinal ischemic complications. The patient had a fast and uneventful
      recovery and is currently doing well 6 months after the procedure. To our
      knowledge, this is the first report in the English literature of successful
      endovascular repair of a TAAA involving visceral arteries with the simple use of
      a tube endograft.

PMID- 17450396
TI  - Species diversity and substrate utilization patterns of thermophilic bacterial
      communities in hot aerobic poultry and cattle manure composts.
AB  - This study investigated the species diversity and substrate utilization patterns
      of culturable thermophilic bacterial communities in hot aerobic poultry and
      cattle manure composts by coupling 16S rDNA analysis with Biolog data. Based on
      the phylogenetic relationships of 16S rDNA sequences, 34 thermophilic (grown at
      60 degrees C) bacteria isolated during aerobic composting of poultry manure and
      cattle manure were classified as Bacillus licheniformis, B. atrophaeus,
      Geobacillus stearothermophilus, G. thermodenitrificans, Brevibacillus
      thermoruber, Ureibacillus terrenus, U. thermosphaericus, and Paenibacillus
      cookii. In this study, B. atrophaeus, Br. thermoruber, and P. cookii were
      recorded for the first time in hot compost. Physiological profiles of these
      bacteria, obtained from the Biolog Gram-positive (GP) microplate system, were
      subjected to principal component analysis (PCA). All isolates were categorized
      into eight different PCA groups based on their substrate utilization patterns.
      The bacterial community from poultry manure compost comprised more divergent
      species (21 isolates, seven species) and utilized more diverse substrates (eight
      PCA groups) than that from cattle manure compost (13 isolates, five species, and
      four PCA groups). Many thermophilic bacteria isolated in this study could use a
      variety of carboxylic acids. Isolate B110 (from poultry manure compost), which is
      97.6% similar to U. terrenus in its 16S rDNA sequence, possesses particularly
      high activity in utilizing a broad spectrum of substrates. This isolate may have
      potential applications in industry.

PMID- 17450398
TI  - Percutaneous management of complications (aortoenteric fistula and sac abscess)
      following bypass surgery for abdominal aortic aneurysm.

PMID- 17450395
TI  - Novel and unexpected prokaryotic diversity in water and sediments of the
      alkaline, hypersaline lakes of the Wadi An Natrun, Egypt.
AB  - The phylogenetic diversity of the bacterial and archaeal community in the water
      and sediments of three large lakes of the Wadi An Natrun was investigated using
      16S rRNA clone libraries. The bacterial community was diverse: 769 clones formed
      345 operational taxonomic units (OTUs) defined at 99% 16S rRNA sequence identity.
      The bacterial community in both the water and sediments of the lakes was
      dominated by clones affiliated with the low G + C Gram-type-positive group, alpha
      proteobacteria, and Bacteroidetes, (11-39, 11-30, and 10-37% of OTUs observed,
      respectively), patterns that have been observed in previously described alkaline,
      athalassohaline systems. However, a relatively high proportion of Firmicutess
      related clones in the water of the lakes and alpha-proteobacteria in the
      sediments was observed. The bacterial community composition of the water and
      sediment of the same lake and of different lakes was significantly different (p <
      0.05). Operational taxonomic units related to the gamma-proteobacteria were more
      abundant in the sediment of Lake Fazda, whereas the sediment of Lake UmRisha was
      dominated by members of the delta-proteobacteria. The proportion of gamma
      proteobacterial and Bacteroidetes-affiliated OTUs were predominant in the water
      of Lake UmRisha and differed significantly from other lake waters (chi-squared
      analysis, p < or = 0.01). The more oxygenated and dilute nature of Lake Hamra was
      reflected in its microbial community composition, with the abundance of
      Bacillales sequences in the water, the absence of Halanaerobiales, Clostridiales,
      and Archaea in the water, and the presence of representatives of more phyla such
      as the Actinobacteria, Spirochaetes, and Verrucomicrobia. The archaeal community
      composition appeared less diverse: 589 clones resulted in 198 OTUs defined at 99%
      16S rRNA sequence identity, and all sequences fell into the phylum Euryarchaeota.
      Phylogenetic analysis showed that many of the sequences were distantly related
      (83-90% 16S rRNA sequence identity) to cultured and uncultured archaea, with many
      clones forming clusters that branched deeply within the Euryarchaeota. Forty-two
      and 53% of the bacterial and archaeal clones had less than 90% 16S rRNA sequence
      identity to previously described sequences. This indicates that the water and
      sediments of the Wadi An Natrun harbor a unique and novel prokaryotic diversity
      that is different from what has been described among other alkaline,
      athalassohaline lakes.

PMID- 17450399
TI  - The feasibility of contrast-enhanced ultrasound during uterine artery
      embolization: a pilot study.
AB  - PURPOSE: To evaluate the feasibility of using contrast-enhanced ultrasound (CEUS)
      during uterine artery embolization (UAE) in order to define the correct end-point
      of embolization with complete devascularization of all fibroids. METHODS: In this
      prospective study of 10 consecutive women undergoing UAE, CEUS was performed in
      the angiographic suite during embolization. When the angiographic end-point,
      defined as the "pruned-tree" appearance of the uterine arteries was reached, CEUS
      was performed while the angiographic catheters to both uterine arteries were kept
      in place. The decision whether or not to continue the embolization was based on
      the findings at CEUS. The results of CEUS were compared with those of contrast
      enhanced magnetic resonance imaging (MRI) 1 day as well as 3 months following
      UAE. RESULTS: CEUS was successfully performed in all women. In 4 cases injection
      of particles was continued based on the findings at CEUS despite angiographically
      complete embolization. CEUS imaging at completion of UAE correlated well with the
      findings at MRI. CONCLUSION: The use of CEUS during UAE is feasible and may
      increase the quality of UAE.

PMID- 17450400
TI  - improved patency of transjugular intrahepatic portosystemic shunt: the efficacy
      of cilostazol for the prevention of pseudointimal hyperplasia in swine TIPS
      models.
AB  - PURPOSE: To investigate the efficacy of oral administration of cilostazol to
      inhibit pseudointimal/intimal hyperplasia in swine TIPS models. METHODS:
      Successful TIPS creation was carried out in 11 of 12 healthy young pigs (20-25
      kg). In the treatment group (n = 6), both cilostazol and aspirin were
      administered daily, from the first day of TIPS creation. The control group (n =
      5) was administered only aspirin. The animals were followed-up for 2 weeks and
      then killed. The specimen (including portal vein, hepatic parenchymal tract,
      hepatic vein, and inferior vena cava) and stents were carefully bisected in a
      longitudinal fashion. The control group was compared with the treatment group by
      means of a gross and histologic evaluation of the degree of pseudointimal/intimal
      hyperplasia in the shunt. RESULTS: At the gross evaluation, the control group
      showed considerably more pseudointimal/intimal hyperplasia than the treatment
      group. Using microscopic evaluation, there was a statistically significant
      difference (p < 0.05) in the mean maximum pseudointimal/intimal hyperplasia
      thickness between the control group (2.97 +/- 0.33 mm) and treatment group (0.73
      +/- 0.27 mm). CONCLUSION: Oral administration of cilostazol may have been
      effective in reducing pseudointimal/intimal hyperplasia in swine TIPS models.

PMID- 17450401
TI  - Emergence of HIV-1 drug resistance during antiretroviral treatment.
AB  - Treating HIV-infected patients with a combination of several antiretroviral drugs
      usually contributes to a substantial decline in viral load and an increase in
      CD4(+) T cells. However, continuing viral replication in the presence of drug
      therapy can lead to the emergence of drug-resistant virus variants, which
      subsequently results in incomplete viral suppression and a greater risk of
      disease progression. In this paper, we use a simple mathematical model to study
      the mechanism of the emergence of drug resistance during therapy. The model
      includes two viral strains: wild-type and drug-resistant. The wild-type strain
      can mutate and become drug-resistant during the process of reverse transcription.
      The reproductive ratio [Symbol: see text](0) for each strain is obtained and
      stability results of the steady states are given. We show that drug-resistant
      virus is more likely to arise when, in the presence of antiretroviral treatment,
      the reproductive ratios of both strains are close. The wild-type virus can be
      suppressed even when the reproductive ratio of this strain is greater than 1. A
      pharmacokinetic model including blood and cell compartments is employed to
      estimate the drug efficacies of both the wild-type and the drug-resistant
      strains. We investigate how time-varying drug efficacy (due to the drug dosing
      schedule and suboptimal adherence) affects the antiviral response, particularly
      the emergence of drug resistance. Simulation results suggest that perfect
      adherence to regimen protocol will well suppress the viral load of the wild-type
      strain while drug-resistant variants develop slowly. However, intermediate levels
      of adherence may result in the dominance of the drug-resistant virus several
      months after the initiation of therapy. When more doses of drugs are missed, the
      failure of suppression of the wild-type virus will be observed, accompanied by a
      relatively slow increase in the drug-resistant viral load.

PMID- 17450402
TI  - Gender differences in depressive symptoms among older adults: a cross-national
      comparison: the CLESA project.
AB  - OBJECTIVES: To assess country-specific gender differences in depressive symptoms
      and to explore if exposures and vulnerabilities vary by gender among older men
      and women from four European countries and Israel. METHODS: Data on 4,449
      subjects between 75 and 84 years old were derived from CLESA ("Cross-national
      determinants of quality of life and health services for the elderly". A ratio
      score of depressive symptoms derived form the CESD and GDS scales was regressed
      on education, marital status, living arrangements, comorbidity and disability and
      all interactions of these factors with gender and country. RESULTS: The
      prevalence of depressive symptoms is higher in women than in men in every
      country, except Sweden. Women are more likely to be exposed to socio-structural
      risks, and have poorer health and more disability than men in most of the
      countries. However, women are not more vulnerable to these risk factors.
      CONCLUSIONS: Findings indicate that the female excess in depressive symptoms
      remains after taking into account the higher prevalence of socio-structural and
      health-related risk factors and that older women are not more vulnerable than
      older men to these known risk factors, suggesting the existence of additional
      pathways linked to gender and/or biological sex.

PMID- 17450403
TI  - Mental hospital admission rates of immigrants in Switzerland.
AB  - PURPOSE: This epidemiological study aims to assess the utilisation of inpatient
      psychiatric services by immigrants. Specifically, we address the question of
      gender-specific differences in immigrants and compare the population-based rates
      of males and females from different countries of origin. METHODS: We analysed
      inpatient admission rates from a defined catchment area over a 6-year period by
      means of psychiatric register data. Poisson regression analysis was used to model
      effects of gender, age and country group (immigrants grouped into six categories
      according to their country of origin). RESULTS: Of the total of 28,511 subjects
      consecutively referred to psychiatric inpatient treatment, 4,814 were foreign
      nationals (16.9%). Among immigrants the proportion of female inpatients (38.7%)
      was far lower than in the general population (45.6%; equal proportion of female
      to-total among Swiss inpatients). Immigrants were 37.4 years old on average at
      index admission (Swiss people: 46.3 years), but there were considerable
      differences across country groups. We found three groups with particularly high
      admission rates: male immigrants originating from Turkey, Eastern European and
      'Other' countries (rates >6 per 1,000 population/year). These were admitted as
      inpatients at far higher rates than females from the same countries. In women,
      there was no immigrant group utilising inpatient treatment at a higher level than
      Swiss females. The rates of inpatient admission in males and females was almost
      equal among the Swiss (4.3 per 1,000), as was the case for immigrants from
      Southern, Western/Northern Europe and former Yugoslavia, although on a lower
      level (2.26-3.15 per 1,000). Regression analysis further suggests that country
      effects and age effects are different for males and females, and age effects are
      specific to the country of origin. DISCUSSION: These gender- and interaction
      effects point to inequalities in psychiatric service use in people with different
      migration background. Further research is needed, particularly to understand the
      reasons for the markedly different gender-specific utilisation of psychiatric
      services by some immigrant groups.

PMID- 17450404
TI  - What's in a name? Is accurate recognition and labelling of mental disorders by
      young people associated with better help-seeking and treatment preferences?
AB  - BACKGROUND: The possible benefits or harms of using psychiatric labels in the
      community have been a focus of debate for many decades. The aim of this study was
      to examine associations between the accuracy of labelling of depression or
      psychosis by young people aged 12-25 and their help-seeking, treatment and self
      help preferences, whilst controlling for a range of potential confounding
      factors. METHODS: A randomly selected population sample of 1,207 young people
      aged 12-25 years from several regions of Victoria, Australia, was interviewed via
      a telephone survey. The structured interviews used vignettes of a young person
      with either depression or psychosis followed by a series of questions related to
      recognition of disorder and recommended forms of help and treatment. Multiple
      logistic regression analyses were used to measure the association between a range
      of help-seeking, treatment and self-help preferences and the predictor variables
      of accuracy of recognition, socio-demographic background and exposure to mental
      health problems. RESULTS: Correct labelling of the disorder was the predictor
      variable most frequently associated with choice of appropriate help and treatment
      for both the depression and psychosis vignettes. In regard to self-help
      preferences, correct labelling of the depression vignette was only associated
      with being less likely to recommend smoking marijuana to relax. Correct labelling
      of the psychosis vignette, or labelling it as depression, was associated with
      being less likely to recommend dealing with the problem alone. CONCLUSION: These
      findings support the view that improving the use of psychiatric labels by young
      people is beneficial, because it facilitates appropriate help-seeking and
      treatment choice. The label may be the cue to activating a schema about
      appropriate action to take.

PMID- 17450405
TI  - [Dementia - new perspectives for clinical research and practise].

PMID- 17450406
TI  - [Subjective perception of and coping with dementia in its early stages. A
      qualitative interview study with people with dementia and their relatives -
      SUWADEM].
AB  - The study SUWADEM has completed the long overdue transition from objective to
      subjective research in the field of dementia in Germany. The perception and
      coping processes are reconstructed on the basis of 25 interviews with people with
      dementia (Pwids) and their family members. Data collection and analysis were
      conducted on principle of a qualitative research method, the "Grounded Theory".
      The subjective experience of dementia was presented in a biopsycho-social
      perspective. On the basis of the identified subjective ageing and disease
      theories, Pwids evaluate their perceived cognitive and functional deficits.
      According to the evaluation outcome the emotional distress varies. The lack of
      insight into the disease (anosognosia) in the early stage is mainly due to
      psychological (e.g. internalised stereotypes concerning old age) and social
      factors (e.g. undifferentiated subjective disease theories of person in
      authority). Within the framework of the disease coping process, anosognosia is a
      function of different forms of self-protection: (1) The regulation of emotions
      and the stabilisation of the sense of self-worth, (2) resistance to
      stigmatisation, (3) defence of one's own autonomy. The results indicate the
      importance of public relations work, which is intended to raise public awareness
      of the early stages of dementia. In addition Pwids have to be active partners in
      dementia research and in the development of support structures. Finally the
      development and evaluation of person-centered single- and group-interventions is
      absolutely necessary.

PMID- 17450407
TI  - [On disclosing a diagnosis of dementia].
AB  - Disclosing a diagnosis of dementia to the patient has become a scientific topic
      only in the last decade. This review gives an up-to-date account of ongoing
      research. After an introductory discussion of the pros and cons, the
      unsatisfactory situation of disclosure in the European Union is analysed.
      Afterwards, the wish of being told a diagnosis of dementia among healthy old
      people, people with dementia and their relatives is described. The first
      empirical studies about coping with the diagnosis are presented. Suggestions of
      new directions in coping research are made. Finally, recommendations for
      communicating the diagnosis to the patient and the family are given.

PMID- 17450408
TI  - [Efficiency of specific neuropsychological and clinical-psychological
      interventions in old age].
AB  - Most of the time, the effect of neuropsychological and clinical-psychological
      interventions for older people with cognitive deficits compared with the medical
      treatment is underestimated. Most times the effect of neuropsychological and
      clinical-psychological interventions in old aged people with cognitive deficits
      is seen lower than those of medical treatment. The aim of the present paper is to
      point out the possibilities and scope of those nonpharmacologic interventions by
      discussing new literature. All interventions have to be based on a specific
      geriatric assessment including neuropsychological testing, which defines the
      structure of the treatment. In the progress of dementia all interventions have to
      be changed from training of cognitive functions to social and emotional aspects.
      A combination with physical activities seems to be more effective. From this
      point of view psychological interventions can be seen as effective as medical
      treatment and have to be combined with them but further research has to be done.

PMID- 17450410
TI  - [Images and discourses of ageing--annotations to the state of research].
AB  - Up to now, images of ageing are considered unilaterally from an individualising
      perspective in which the cause for negative images as well as the starting point
      for potential change is localised in cognitive attitude patterns. In this
      contribution we plead for a conceptual extension of the research on images of
      ageing which also encloses societal discourses and body images. Images and
      discourses of ageing and associated ideas of man also reflect the intentions and
      images of social interest groups. Hence, an important research assignment should
      be to examine existing images and discourses of ageing critical for their
      ideological, cultural and societal implications.

PMID- 17450409
TI  - [Delirium with dementia].
AB  - In the past the concept of delirium was associated with different diseases. Even
      today numerous synonyms of delirium exist. The author gives an overview of the
      definition of delirium in the past and today. The paper presents epidemiological
      data, diagnostic criteria and differential diagnoses of delirium for patients
      suffering from dementia. Pathological mechanisms, risk factors and triggers as
      well as different forms of delirium for patients suffering from dementia are
      discussed. Diagnostics and differential diagnostics are discussed and possible
      medicamentous and non-medicamentous therapy procedures as well as the prevention
      of delirium are shown. The author points out the necessity of education and
      training of medical staff to prevent or to diagnose early delirium for patients
      suffering from dementia and to start therapy as early as possible.

PMID- 17450411
TI  - Depression among caregivers of the frail elderly in Japan before and after the
      introduction of the Public Long-Term Care Insurance System.
AB  - Cross sectional studies were conducted in five towns in Japan before and after
      the introduction of the Long-term Care Insurance System (LTCIS), in order to
      evaluate the factors relating to depression among family caregivers for the frail
      elderly. Depressive caregivers were more likely to consult with their doctors, to
      be in poor health, to care for demented elderly with behavioral disturbances than
      the non-depressive caregivers both before and after the LTCIS. Before LTCIS,
      depressive caregivers were more likely to attend to the elderly for more than 16
      hours per day than their counterparts. After the LTCIS, depressive caregivers
      were more likely to be a spouse, to care for a frail elderly male, and less
      likely to be able to go out without accompanying the elderly than their
      counterparts. Even after the introduction of LTCIS, half of the caregivers were
      depressive. It is suggested that a government agency should be created to support
      not only the frail elderly but also their caregivers.

PMID- 17450417
TI  - Impact of a primary care intervention on smoking, drinking, diet, weight, sun
      exposure, and work risk in families with cancer experience.
AB  - BACKGROUND: Modifying multiple behavior risks is a promising approach to reduce
      cancer risk. Primary prevention advices of the European Code against Cancer were
      included in an educational intervention (EI) using social cognitive theories for
      motivating families with cancer experiences to adopt six cancer prevention
      behaviors. METHODS: A randomized clinical controlled trial recruited 3,031
      patients from Primary Care among cancer patients' relatives. The experimental
      group (EG) received four EI, one EI every six months, focused on tobacco,
      alcohol, diet, weight, sun and work, and based on social cognitive models. The
      impact of the first three EI was calculated measuring at baseline and 18 months
      later: (a) The percentage of people with each risk behavior; (b) The score
      reached in a Total Cancer Behavioral Risk (TCBR) indicator; (c) The Odds Ratios
      at the post-test. RESULTS: Five risk behaviors decreased significantly more
      (p<0.01) in the EG than in the CG: Smoking (OR=0.662), drinking (OR=0.504), diet
      (OR=0.542), weight (OR=0.698), and sun (OR=0.389). The TCBR indicator also
      decreased an average of nearly 5 points (28.42 vs. 23.82), significantly more
      (p<0.001) in the EG. CONCLUSION: Families with cancer experiences changed five
      cancer risk behaviors when approached in Primary Care with interventions based on
      social cognitive models.

PMID- 17450416
TI  - Chloroplast ribosome release factor 1 (AtcpRF1) is essential for chloroplast
      development.
AB  - To study the functions of nuclear genes involved in chloroplast development, we
      systematically analyzed albino and pale green Arabidopsis thaliana mutants by use
      of the Activator/Dissociation (Ac/Ds) transposon tagging system. In this study,
      we focused on one of these albino mutants, designated apg3-1 (for a lbino or p
      ale g reen mutant 3). A gene encoding a ribosome release factor 1 (RF1) homologue
      was disrupted by the insertion of a Ds transposon into the APG3 gene; a T-DNA
      insertion into the same gene caused a similar phenotype (apg3-2). The APG3 gene
      (At3g62910) has 15 exons and encodes a protein (422-aa) with a transit peptide
      that functions in targeting the protein to chloroplasts. The amino acid sequence
      of APG3 showed 40.6% homology with an RF1 of Escherichia coli, and
      complementation analysis using the E. coli rf1 mutant revealed that APG3
      functions as an RF1 in E. coli, although complementation was not successful in
      the RF2-deficient (rf2) mutants of E. coli. These results indicate that the APG3
      protein is an orthologue of E. coli RF1, and is essential for chloroplast
      translation machinery; it was accordingly named AtcpRF1. Since the chloroplasts
      of apg3-1 plants contained few internal thylakoid membranes, and chloroplast
      proteins related to photosynthesis were not detected by immunoblot analysis,
      AtcpRF1 is thought to be essential for chloroplast development.

PMID- 17450418
TI  - A comparison of the anatomic distribution of cutaneous melanoma in two
      populations with different levels of sunlight: the west of Scotland and
      Queensland, Australia 1982-2001.
AB  - To explore whether the anatomic distribution of melanoma differs with ambient
      sunlight levels, we compared age- and site-specific melanoma incidence in two
      genetically similar populations from different geographic regions. We ascertained
      all new cases of invasive cutaneous melanoma in the west of Scotland and
      Queensland 1982-2001. Melanoma incidence was calculated for four anatomic regions
      (head and neck, trunk, upper and lower limbs), standardized to the European
      population and adjusted for relative surface area of each site. Highest rates
      among males aged <40 years and 40-59 years were observed on the trunk, but on the
      upper limbs among Queensland females and lower limbs among Scottish females.
      After age 60, melanoma rates were highest on the head and neck in both sexes. In
      both sexes and at all ages, lower limb melanomas were more common in Scotland
      than expected from the Queensland population. These analyses indicate that while
      the overall distribution of melanoma is similar in populations with different
      levels of ambient sunlight, important differences remain. Identifying the causes
      of these differences is likely to provide better understanding of how sunlight
      causes melanoma.

PMID- 17450419
TI  - Relation of waste generation and composition to socio-economic factors: a case
      study.
AB  - To develop an effective waste management strategy for a given region, it is
      important to know the amount of waste generated and the composition of the waste
      stream. Past research has shown that the amount of waste generated is
      proportional to the population and the average mean living standards or the
      average income of the people. In addition, other factors may affect the amount
      and composition of waste. These are climate, living habits, level of education,
      religious and cultural beliefs, and social and public attitudes. This paper
      presents the findings of a study carried out in a suburban municipal area in Sri
      Lanka to determine the solid waste generation rate and waste composition based on
      field surveys and to determine the related socio-economic factors. A database was
      developed that included information on the quantity and composition of waste
      generated in a sample of households in the study area over a time period. The
      collected data was analysed to relate waste generation and composition data to
      various socio-economic factors. Over 400 sample households were selected for the
      study using a stratified random sampling methodology based on municipal wards and
      property values. A technique that considers both the number of households in a
      particular income group (property value range) and the standard deviation of
      property values within a given income group was used to determine the appropriate
      sample size for each municipal ward. Through category and regression analyses,
      the quantities of waste and waste composition were related to several socio
      economic factors. The paper describes the basis for the sample selection, the
      methodology adopted for data collection, the socio-economic parameters used for
      the analysis, and the relationships developed from the analysis.

PMID- 17450420
TI  - Impact of serum albumin and body-mass index on survival in hemodialysis patients.
AB  - A low body mass index (BMI) and serum albumin are associated with increased risk
      of mortality in patients with chronic kidney disease (CKD). The purpose of this
      study was to evaluate BMI and serum albumin as predictors of all-cause and
      cardiovascular (CV) mortality in hemodialysed (HD) patients. We describe the
      results of a five-year retrospective observational study with 187 HD patients
      (54.9 +/- 15.6 years old, 54% men, and 46% suffering from diabetes) from RenalCor
      Clinic in Rio de Janeiro, Brazil. The influence of serum albumin levels and BMI
      (determined every three months) over all-cause mortality was examined using a Cox
      model, while the influence of the same factors over CV mortality among all-cause
      mortality was modeled through a logistic regression. During the five years, 26.7%
      of the patients died, 62% of which due to CV disease (CVD). Analysis by the Cox
      model showed that low serum albumin and low BMI were significant predictors of
      mortality. Patients with higher BMI had a lower hazard of death for all-cause
      mortality (hazard ratio [HR] = 0.92; P ( )= 0.035) and a 1 g/l increase in serum
      albumin was associated with significantly lower hazard of death (hazard ratio =
      0.9679; P < 0.001). The highest BMI value (>30 kg/m(2)) was significantly
      associated with an increase of odds of CV mortality (odds ratio = 1.22, P =
      0.03). We confirm here in a Brazilian cohort of hemodialysis patients that both
      low BMI (<19 kg/m(2)) and hypoalbuminemia are strong predictors of death.

PMID- 17450421
TI  - Cytomegalovirus disease with Guillain-Barre syndrome in a cadaver renal allograft
      recipient: cause or coincidence.
AB  - Anecdotal reports of acute inflammatory demyelinating polyneuropathy (Guillain
      Barre syndrome) with cytomegalovirus (CMV) suggested as the etiological agent
      have been described in transplant recipients with poor prognosis. We describe a
      48-year-old man, a cadaveric renal allograft recipient on cyclosporine,
      mycophenolate mofetil and prednisolone, who developed febrile illness with
      unexplained anemia followed by progressive weakness of the upper and lower limbs.
      He was diagnosed as a case of Guillain-Barre syndrome (GBS). His CMV serology was
      positive by polymerase chain reaction (PCR). We treated him with both gancyclovir
      and intravenous immunoglobulins within a week of the onset of GBS and observed
      rapid recovery. Thus, search for CMV is warranted in transplant patients
      presenting with GBS, as early initiation of treatment with gancyclovir and
      immunoglobulins can help expedite recovery.

PMID- 17450422
TI  - Drug therapy problems found in ambulatory patient populations in Minnesota and
      South Australia.
AB  - OBJECTIVE: To compare drug therapy problems identified by pharmacists in two
      patient samples, the Minnesota Sample and the South Australian Sample. METHODS:
      Two patient samples were selected for this comparison. Both sets of patients
      received pharmaceutical care services from pharmaceutical care practitioners
      between March 1999 and February 2000. The two databases were then compared for
      common drug therapy problems. MAIN OUTCOME MEASURE: Comparison of drug therapy
      problems in the two samples. RESULTS: Both patient samples included patients who
      were 40 years of age or older. The Minnesota Sample included 1,598 individual
      patients, of whom 70% experienced one or more drug therapy problems at some time
      during their care. The South Australian Sample included a total of 982 patients
      of whom 90% experienced one or more drug therapy problems at some time during
      their care. Conditions common to both patient samples include hypertension,
      diabetes, arthritis, ischemic heart disease, and osteoporosis. Frequently
      occurring drug therapy problems in the Minnesota Sample included the need for
      additional drug therapy, dosage too low and non-compliance and in the South
      Australian Sample included non-compliance, additional drug therapy and
      ineffective drug therapy. Frequent drug therapy problems associated with medical
      conditions in the Minnesota Sample included addition of new therapies for
      conditions such as arthritis, hypertension, hyperlipidemia and allergic rhinitis,
      while for the South Australian Sample included compliance issues with conditions
      such as asthma, diabetes mellitus, angina and digestive disorders. Frequent drug
      therapy problems with associated drug classes in the Minnesota Sample included
      additional therapy for classes such as salicylates and calcium supplements, while
      in the South Australian Sample included the need for therapy for pneumococcal
      vaccines, salicylates, calcium supplements and tetanus vaccines. CONCLUSION:
      These data demonstrate that this age group has significant drug therapy problems
      and therefore emphasize the need for pharmaceutical care services in this
      population. The provision of pharmaceutical care by experienced practitioners can
      result in improved recognition of the full range of drug therapy problems
      confronting patients. Analyses such as those presented here provide information
      to better focus the training of practitioners based on the most frequently
      encountered health problems and the nature of common drug therapy problems in the
      community setting.

PMID- 17450423
TI  - Small-cell lung cancer patients are just 'a little bit' tired: response shift and
      self-presentation in the measurement of fatigue.
AB  - BACKGROUND: Response shift has gained increasing attention in the measurement of
      health-related quality of life (QoL) as it may explain counter-intuitive findings
      as a result of adaptation to deteriorating health. OBJECTIVE: To search for
      response shift type explanations to account for counter-intuitive findings in QoL
      measurement. METHODS: Qualitative investigation of the response behaviour of
      small-cell lung cancer (SCLC) patients (n = 23) in the measurement of fatigue
      with The European Organization for Research and Treatment of Cancer Core Quality
      of Life Questionnaire (EORTC QLQ-C30) question 'were you tired'. Interviews were
      conducted at four points during 1st line chemotherapy: at the start of
      chemotherapy, 4 weeks later, at the end of chemotherapy, and 6 weeks later.
      Patients were asked to 'think aloud' when filling in the questionnaire. RESULTS:
      Fifteen patients showed discrepancies between their answer to the EORTC question
      'were you tired' and their level of fatigue spontaneously reported during the
      interview. These patients chose the response options 'not at all' or 'a little'
      and explained their answers in various ways. In patients with and without
      discrepancies, we found indications of recalibration response shift (e.g. using a
      different comparison standard over time) and of change in perspective (e.g.
      change towards a more optimistic perspective). Patients in the discrepancy group
      reported spontaneously how they dealt with diagnosis and treatment, i.e. by
      adopting protective and assertive behaviour and by fighting the stigma. They
      distanced themselves from the image of the stereotypical cancer patient and
      presented themselves as not suffering and accepting fatigue as consequence of
      treatment. CONCLUSION: In addition to response shift, this study suggests that
      'self-presentation' might be an important mechanism affecting QoL measurement,
      particularly during phases when a new equilibrium needs to be found.

PMID- 17450424
TI  - Introducing systems change in the schools: the case of school luncheons and
      vending machines.
AB  - A major public health crisis facing America's society is the increase in child
      and youth obesity, which has seen a fourfold increase in the last four decades.
      Major concerns include what children eat for school lunch and what other foods
      are available in schools. This paper illustrates efforts towards systems change
      in the luncheon program and food vending machines in the Chicago Public Schools.
      We discuss the different factors that lead to such changes using the framework of
      the social ecological model and the soft systems methodology, and we analyze how
      the resulting innovation was implemented and evaluated. First, we present a
      theoretical perspective to explain factors that influence children's eating
      patterns from a systems approach. Second, we discuss the antecedent factors that
      lead to systems change. Finally, we examine challenges to systems change, such as
      resistance to change, different stakeholder priorities, lack of resources,
      institutional bureaucracy, and unrealistic funder expectations.

PMID- 17450425
TI  - Left atrial remodelling contributes to the progression of asymptomatic left
      ventricular systolic dysfunction to chronic symptomatic heart failure.
AB  - Systolic heart failure (HF) is a progressive disorder that often begins with
      asymptomatic left ventricular (LV) systolic dysfunction and culminates in
      symptoms from fluid overload and poor end-organ perfusion. The progression to
      symptomatic HF is accompanied by marked activation of neurohormonal and cytokine
      systems, as well as a series of adaptive LV anatomical and functional changes,
      collectively referred to as LV remodelling. However, the mechanisms underlying
      symptom appearance have not been delineated and the weight of experimental and
      clinical evidence suggests that the development of symptomatic HF occurs
      independently of the haemodynamic status of the patient. The left atrium is a
      muscular chamber strategically located between the left ventricle and the
      pulmonary circulation with important mechanical function (modulation of LV
      filling), which is closely coupled with its endocrine (atrial natriuretic peptide
      synthesis and secretion) and regulatory (contribution to the control of
      sympathetic activity and vasopressin release) functions. In this narrative review
      we provide evidence supporting the concept that left atrial dilation and systolic
      dysfunction (left atrial remodelling) contributes to the progression of
      asymptomatic LV dysfunction to chronic symptomatic systolic HF as it is a
      prerequisite for the development of the pulmonary congestion and marked
      neuronhormoral activity that characterize the symptomatic state.

PMID- 17450426
TI  - Epidemiology of acute heart failure syndromes.
AB  - Acute Heart Failure is a heterogeneous set of syndromes associated with
      significant morbidity and mortality. There are several classifications of acute
      heart failure syndromes (AHFS) based on pathophysiology or clinical presentation.
      In the USA and in Europe, AHFS are the first cause of hospitalization of the
      elderly, and the leading health care cost. Despite this clinical and social
      importance, AHFS have received little attention from clinicians and researchers.
      Recently published epidemiological studies described clinical presentation,
      characteristics and treatment of over 100,000 patients hospitalized with AHFS.
      These studies also underlined the poor, short, and medium term prognosis,
      especially for the most severe patients admitted to an intensive care unit, with
      in-hospital mortality of 28%. Further epidemiological and clinical research is
      needed to improve our understanding of AHFS, thereby enhancing patient care.

PMID- 17450429
TI  - Legal and ethical issues in the international transaction of donor sperm and
      eggs.
AB  - Pertinent ethical and legal issues in the international transaction of donor
      sperm and eggs are discussed. Firstly, there may be legislative and ethical
      "contradiction" by the local health authority in permitting import of donor
      gametes, due to varying policies on donor reimbursement in different countries.
      This is particularly significant in countries where the underlying principle of
      gamete donation is altruistic motivation, and where reimbursement is given only
      for direct "out-of-pocket" expenses i.e. traveling costs. Secondly, there is a
      lack of clear and coherent internationally-binding legislation and regulatory
      guidelines overseeing the exchange of donor gametes across international borders.
      In particular, provisions should be made for donor traceability if gametes are
      sourced from abroad. Thirdly, in the case of "frozen-egg donation" from abroad,
      patients must rightfully be informed that current cryopreservation technology is
      still sub-optimal, and all studies have consistently shown that the chances of
      conception are always lower with "frozen-eggs" compared to freshly-retrieved
      eggs. Finally, regulatory safeguards should be put in place to prevent fertility
      clinics and medical professionals from "re-selling" imported donor gametes at a
      profit to the patient, since it would be thoroughly unprofessional for them to
      earn a profit simply through the 'brokerage' of donated human material.

PMID- 17450427
TI  - Urban environmental health hazards and health equity.
AB  - This paper outlines briefly how the living environment can affect health. It
      explains the links between social and environmental determinants of health in
      urban settings. Interventions to improve health equity through the environment
      include actions and policies that deal with proximal risk factors in deprived
      urban areas, such as safe drinking water supply, reduced air pollution from
      household cooking and heating as well as from vehicles and industry, reduced
      traffic injury hazards and noise, improved working environment, and reduced heat
      stress because of global climate change. The urban environment involves health
      hazards with an inequitable distribution of exposures and vulnerabilities, but it
      also involves opportunities for implementing interventions for health equity. The
      high population density in many poor urban areas means that interventions at a
      small scale level can assist many people, and existing infrastructure can
      sometimes be upgraded to meet health demands. Interventions at higher policy
      levels that will create more sustainable and equitable living conditions and
      environments include improved city planning and policies that take health aspects
      into account in every sector. Health equity also implies policies and actions
      that improve the global living environment, for instance, limiting greenhouse gas
      emissions. In a global equity perspective, improving the living environment and
      health of the poor in developing country cities requires actions to be taken in
      the most affluent urban areas of the world. This includes making financial and
      technical resources available from high-income countries to be applied in low
      income countries for urgent interventions for health equity. This is an
      abbreviated version of a paper on "Improving the living environment" prepared for
      the World Health Organization Commission on Social Determinants of Health,
      Knowledge Network on Urban Settings.

PMID- 17450430
TI  - Cumulative exposure to high estradiol levels during the follicular phase of IVF
      cycles negatively affects implantation.
AB  - PURPOSE: To investigate the effect of the cumulative exposure to estradiol (E(2))
      during the follicular phase on IVF outcome. METHODS: Patients were stimulated
      with recombinant FSH after GnRH agonist suppression and had a day 3-embryo
      transfer. Estrogen exposure was determined as the area under the curve (AUC) for
      serum E(2) levels measured from the first day of stimulation through the day
      after hCG administration. RESULTS: E(2) AUC thresholds for 10th and 90th
      percentiles were 4704 pg/ml and 16338 pg/ml, respectively. The pregnancy and
      implantation rates were highest in the 10th-90th percentile group, and were
      statistically higher in this group than in the >90th percentile group (54.6% vs.
      33.3% and 24.8% and 12.9%, respectively, for pregnancy and implantation rates, P
      < 0.05). Recovered mature oocytes, fertilization, and number and mean score of
      transferred embryos were similar. CONCLUSIONS: High cumulative E(2) exposure
      during the follicular phase of IVF cycles has detrimental effects on
      implantation.

PMID- 17450431
TI  - Natural cycle cryo-thaw transfer may improve pregnancy outcome.
AB  - OBJECTIVE: To compare natural vs. hormone replacement treatment (HRT) for cryo
      thaw embryo transfer cycles in patients with frozen embryos from previous ART.
      DESIGN AND SETTINGS: Retrospective chart review of 164 patients (242 cycles) who
      underwent natural or HRT cryo-thaw embryo transfer between January 2002 and April
      2005. MAIN OUTCOME MEASURES: Pregnancy rates per transfer in natural and HRT cryo
      thaw cycles. RESULTS: The pregnancy rate per transfer was higher with natural
      cycles (36.76% vs. 22.99%, P = 0.0298). There was no statistical difference in
      mean age, endometrial thickness, and average embryo quality in successful cycles.
      Mean endometrial thickness prior to transfer was greater in natural cycles (9.95
      vs. 8.89 mm, P < 0.001). Mean serum estradiol levels were higher in the HRT group
      prior to transfer (526.1 vs. 103.8 pg/ml, P < 0.001), and were found to be lower
      in women who achieved pregnancy (337.1 vs. 433.3 pg/ml, P = 0.0136). CONCLUSION:
      Hormone replacement in preparation for cryo-thaw transfer of embryos was found to
      be associated with decreased pregnancy rates in comparison to natural cycle cryo
      thaw transfer. Greater endometrial thickness was achieved with lower serum
      estradiol levels in patients undergoing natural cycles, suggesting that higher
      estradiol levels during HRT cycle may interfere with the window of implantation.

PMID- 17450432
TI  - Severe oligoasthenoteratozoospermias, secretory and obstructive azoospermias:
      motility as a criterion of sperm viability.
AB  - PURPOSE: Comparison of pregnancy rates in cases of Secretory Azoospermias (SA),
      Obstructive Azoospermias (OA) and severe Oligoasthenoteratozoospermias (OATZ).
      Evaluation of sperm motility as a quality criterion. METHODS: In SA cases (n =
      35), 9 samples were cryopreserved. In OA cases (epididymal aspiration: n = 91;
      testicular biopsy: n = 206), all samples were cryopreserved. 596 OATZ ejaculates
      were included. RESULTS: In SA cases, 2 pregnancies were achieved from 9 ICSI
      cycles. In OA, motile sperm rates were higher in testicular biopsies. After
      thawing sperm motility was not different between testicular and epididymal
      origin. 2 pregnancies were achieved with immotile testicular sperm after thawing,
      but none with immotile epididymal sperm. In OATZ cases, one pregnancy was
      obtained from the 9 cryopreserved ejaculates and 35.3% with fresh motile sperm.
      CONCLUSIONS: In SA cases, the use of donor sperm is recommended due to the lower
      pregnancy rate achieved. Motility, before and after cryopreservation, as a
      criterion of sperm viability is discussed and its use should be reconsidered in
      some cases.

PMID- 17450433
TI  - Silver-Russell syndrome in a girl born after in vitro fertilization: partial
      hypermethylation at the differentially methylated region of PEG1/MEST.
AB  - PURPOSE: The prevalence of low birth weight (LBW) is increased in subjects born
      after assisted reproduction technology (ART), and defective imprinting has
      frequently been identified in patients with Beckwith-Wiedermann and Angelman
      syndromes conceived by ART. Thus, we examined methylation pattern in a girl born
      after ART who had Silver-Russell syndrome (SRS) which can be caused by maternal
      uniparental disomy for chromosome 7 and by hypomethylation of the differentially
      methylated region (DMR) of H19. METHODS: We examined methylation status of 31
      cytosines at the CpG dinucleotides in the DMR of PEG1/MEST on 7q32.2 and 23
      cytosines at the CpG dinucleotides in the DMR of H19 on 11p15, using leukocyte
      genomic DNA. RESULTS: Eight of the 31 cytosines in the patient and four of the 31
      cytosines in the father were hypermethylated in the PEG1/MEST-DMR. In the H19
      DMR, no abnormal methylation pattern was identified in the patient. CONCLUSION:
      The results suggest that hypermethylation of paternally expressed genes including
      PEG1/MEST, which usually have growth-promoting effects, may be relevant to LBW in
      subjects conceived by ART.

PMID- 17450434
TI  - Significance of ovarian macrophages in the follicular aspirates from ART
      patients.
AB  - PURPOSE: To evaluate the percentages of macrophages present in granulosa cells
      (GC) cultures from patients with different responses to the hyperstimulation, in
      relation to the percentages of apoptotic cells (ApC), as well as to the release
      of cytokines. METHODS: We studied 42 patients: 12 Hyporesponders, (with < or =4
      follicles), 15 Normoresponders, (5-14 follicles), and 15 Hyperresponders, (> or
      =15 follicles). In GC cultures percentages of macrophages and ApC were counted
      and, in the conditioned media, cytokines were measured. RESULTS: Percentages of
      macrophages were significantly higher in GC cultures from Hyporesponders compared
      with Hyperresponders patients. Also, the percentages of ApC cells were the
      highest in Hyporesponders. On the contrary, cytokines concentrations were the
      lowest in this group. CONCLUSIONS: The low ovarian response is probably due to
      the decreased angiogenesis, which in turn produces increased apoptosis and
      decreased production of cytokines. The increased percentage of macrophages could
      be related to increased frequency of apoptotic cells.

PMID- 17450435
TI  - Bilateral ovarian abscesses following transvaginal oocyte retrieval for IVF: a
      case report and review of literature.
AB  - Ultrasound-guided transvaginal oocyte retrieval (TVOR) is a relatively simple and
      atraumatic method with rare complications as well as the possibility of doing it
      under sedation. It has become the method of choice in most IVF centres, because
      it results in excellent oocyte yields, with increased speed and excellent
      follicle and major pelvic vessel visualization, thereby decreasing the
      probability of vessel puncture [1]. However, the technique is not without risk
      such as pelvic infection, bleeding secondary a blood vessel puncture or pelvic
      visceral trauma. Consumption coagulopathy is a serious complication of pelvic
      infection and sepsis which can be life threatening if not diagnosed and corrected
      early, especially if surgical intervention is required. We present a case of
      bilateral ovarian abscesses following transvaginal oocyte retrieval showing early
      signs of consumption coagulopathy.

PMID- 17450436
TI  - Birth after transfer of frozen-thawed vitrified biopsied blastocysts.
AB  - PURPOSE: To present a case describing the birth of a healthy female after the
      replacement of vitrified biopsied embryos after Preimplantation Genetic
      Diagnosis. METHOD: A descriptive case report of a single patient. RESULTS: Our
      patient carrier of an X-linked disease became pregnant and as a result a healthy
      girl was born. CONCLUSIONS: This report shows that blastocysts obtained from
      biopsied embryos can be successfully cryopreserved by a simple, secure and low
      cost vitrification method using a Hemi-straw support.

PMID- 17450437
TI  - Mid-term results of stapled hemorrhoidopexy for third- and fourth-degree
      hemorrhoids--correlation with the histological features of the resected tissue.
AB  - BACKGROUND: Stapled hemorrhoidopexy is used to remove a circumferential strip of
      mucosa and submucosa about 4 cm above the dentate line, in order to restore the
      correct anatomical relationships of the anal canal structures. We evaluated the
      histological features of the resected tissue obtained after stapled
      hemorrhoidopexy with correlation to the short-term and mid-term results. METHODS:
      This retrospective study evaluated 234 cases of stapled hemorrhoidopexy. Data
      concerning postoperative bleeding, anal pain, incontinence, stenosis, and
      recurrence of hemorrhoids were collected from hospital and outpatient clinic
      records. Histologic slides were examined for the type of epithelium, presence of
      muscle fibers, nerve endings, and degree of vascular ectasia. RESULTS: Some 52%
      of the biopsies revealed on the surface a combination of glandular with squamous
      epithelium, meaning a stapling line at the level of the transitional zone/dentate
      line. Smooth muscle fibers were more frequent as the stapling line approached the
      level of the dentate line/transitional zone (p = 0.0028). Internal sphincter
      fibers were present in 36% of the cases, yet there were no cases of anal
      incontinence. Inclusion of merely squamous epithelium in the resected tissue
      correlated with severe postoperative pain persisting one week after surgery (p <
      0.0001), whereas the concurrent presence of squamous and glandular epithelium
      correlated only with severe pain on the first postoperative day (p = 0.018).
      Nerve endings were more frequent in patients with anal pain one week after
      surgery (p = 0.02). The rate of recurrence of symptoms was 3%, which did not
      correlate with any of the histological parameters tested. CONCLUSIONS: Though
      stapled hemorrhoidopexy is performed according to well-established technical
      guidelines, it is too difficult to be standardized.

PMID- 17450438
TI  - Laparoscopic surgery of the spleen.

PMID- 17450439
TI  - A rare case of solitary osteochondroma of the dens of the C2 vertebra.
AB  - We report an extremely rare case of a 22-year-old man with an asymptomatic
      osteochondroma of the dens of C2 vertebra accidentally found during a brain CT
      scan examination.

PMID- 17450440
TI  - Breastfeeding and risk of ovarian cancer in two prospective cohorts.
AB  - OBJECTIVE: To describe the association between breastfeeding and ovarian cancer
      risk in two prospective cohorts. MATERIALS & METHODS: We pooled data from the
      Nurses' Health Study and Nurses' Health Study II. There were 391 cases of
      epithelial ovarian cancer diagnosed among 149,693 parous women with up to 16
      years of follow-up. Data were analyzed using multivariate Cox proportional
      hazards models, controlling for age, parity, duration of oral contraceptive use,
      tubal ligation, and age at menarche. RESULTS: Ever breastfeeding was associated
      with a non-significant reduction in ovarian cancer risk compared with never
      breastfeeding (RR=0.86, 95% CI 0.70-1.06); the median duration of breastfeeding
      among women who breastfed was nine months. Breastfeeding of 18 or more months was
      associated with a significant decrease in ovarian cancer risk compared to never
      breastfeeding (RR=0.66, 95% CI 0.46-0.96). For each month of breastfeeding the
      relative risk decreased by 2% (RR=0.98 per month, 95% CI 0.97-1.00). CONCLUSIONS:
      These data support a linear inverse association between breastfeeding and risk of
      epithelial ovarian cancer.

PMID- 17450441
TI  - History of diabetes mellitus and subsequent prostate cancer risk in the NIH-AARP
      Diet and Health Study.
AB  - OBJECTIVE: A history of diabetes has been hypothesized to decrease prostate
      cancer risk, but studies have not always considered confounding or effect
      modification by dietary or lifestyle factors. METHODS: We examined the
      association between diabetes history and subsequent prostate cancer risk in
      328,316 men enrolled in the NIH-AARP Diet and Health Study. Participants were
      ages 50-71 years and without a prostate cancer diagnosis at baseline in 1995. A
      prior history of physician-diagnosed diabetes was assessed using a self
      administered mailed questionnaire. Cases of prostate cancer were ascertained by
      matching the cohort to state cancer registries. Multivariable relative risks (RR)
      and 95% confidence intervals (CI) of prostate cancer were estimated using Cox
      regression. RESULTS: During 5 years and 1,432,676 person-years of follow-up,
      11,193 prostate cancer cases were ascertained. The age-adjusted and multivariable
      RRs of prostate cancer comparing men with diabetes to those without diabetes were
      0.69 (95% CI=0.64, 0.74) and 0.71 (95% CI=0.66, 0.76), respectively, indicating
      no important confounding. The inverse association between diabetes and prostate
      cancer was particularly strong among men in the highest category of routine
      physical activity at work or home (RR=0.41; 95% CI=0.23, 0.74; p value for test
      of interaction = 0.03). Findings were similar for organ-confined and advanced
      prostate cancer. CONCLUSION: Results from this large prospective study suggest
      that a history of diabetes is associated with a decreased risk of prostate
      cancer. The relationship strengthened with high levels of routine physical
      activity. Because increased physical activity is associated with lower
      circulating levels of insulin and testosterone, our findings support a role of
      hypoinsulinemia and low androgenicity linking diabetes to decreased prostate
      cancer risk.

PMID- 17450442
TI  - Gastrointestinal cytoprotection: from basic science to clinical perspectives.
AB  - An essential point of cytoprotection is that the prostaglandins are able to
      prevent chemical-induced gastric mucosal damage without affecting gastric acid
      secretion, this being originally suggested as a property specific to
      prostaglandins. Since then gastrointestinal cytoprotection has been shown with
      various agents (anticholinergic agents, H(2)RA, growth factors) and retinoids the
      latter differing from the actions of vitamin A. In examining the various
      components of gastrointestinal cytoprotection we have performed studies in
      isolated cells, stable cell lines, animal experiments, healthy human subjects,
      and in patients with gastrointestinal diseases. Our attention has focused on the
      effects of cytoprotective agents on cellular viability, mitochondrial and DNA
      damage, oxygen free radicals, natural antioxidant systems, mucosal biochemistry,
      vascular events, gastrointestinal mucosal protection as well as in their
      prevention of different human diseases. This paper gives a short overview on the
      different approaches for the exploring gastrointestinal cytoprotection.

PMID- 17450443
TI  - The prevalence of Helicobacter pylori infection and the status of gastric acid
      secretion in patients with gastroesophageal junction adenocarcinoma in Japan.
AB  - We have previously reported that H. pylori infection prevents reflux esophagitis
      (RE) and Barrett's esophagus (BE) by decreasing gastric acid secretion.
      Gastroesophageal (GE) junction adenocarcinoma, including Barrett's
      adenocarcinoma, has been thought to be a complication of gastroesophageal reflux
      disease. However, the relationship between H. pylori infection, gastric acid
      secretion and GE junction adenocarcinoma had not yet been investigated in Japan.
      We demonstrated that the status of gastric acid secretion was higher in patients
      with GE junction adenocarcinoma than in patients with early gastric cancer (EGC),
      and that the level was the same in patients with RE and those with BE. We also
      found that the prevalence of H. pylori infection in patients with GE junction
      adenocarcinoma was significantly lower than that in patients with EGC, although
      not as low as that in patients with RE and BE, suggesting that preservation of
      gastric acid secretion may be important for the development of GE junction
      adenocarcinoma in Japanese people, regardless of the presence of H. pylori
      infection.

PMID- 17450444
TI  - The preventive effect of Daikenchuto on postoperative adhesion-induced intestinal
      obstruction in rats.
AB  - The present study investigated the effect of Daikenchuto (DKT) on postoperative
      intestinal adhesion in rats. We evaluated the effects of DKT, constituent medical
      herbs and active compounds on talc-induced intestinal adhesion in rats and DKT
      induced contractions using isolated guinea pig ileum. DKT significantly prevented
      adhesion formation, and this action was inhibited by pretreatment with atropine
      or ruthenium red. The constituent medical herbs, Zanthoxylum Fruit and Maltose
      Syrup Powder significantly prevented adhesion formation. Moreover, hydroxy
      sanshool (HS) prevented adhesion formation, and this action was inhibited by
      pretreatment with ruthenium red. In contrast, DKT-induced contractions were
      inhibited by tetrodotoxin, atropine, and capsazepine. These results suggested
      that DKT had a preventive action on postoperative adhesive intestinal
      obstruction, and that this action was mediated by sensory and cholinergic nerves.
      Furthermore, HS was found to be one of the active compound of DKT, and its action
      was mediated by sensory nerves.

PMID- 17450445
TI  - Various stress proteins protect gastric mucosal cells against non-steroidal anti
      inflammatory drugs.
AB  - Gastric mucosal cell death induced by non-steroidal anti-inflammatory drugs
      (NSAIDs) is suggested to be involved in NSAID-induced gastric lesions. Therefore,
      cellular factors that suppress this cell death are important for protection of
      the gastric mucosa from NSAIDs. When cells are exposed to various stressors,
      including NSAIDs, they induce a number of proteins, so-called stress proteins, in
      order to protect themselves against such stressors. Stress proteins contain
      cytosolic molecular chaperons (such as heat shock proteins), endoplasmic
      reticulum molecular chaperons (such as glucose-regulated proteins) and heme
      oxygenase-1. We recently showed that (i) these stress proteins are up-regulated
      by NSAIDs both in vitro and in vivo; (ii) these up-regulation make gastric
      mucosal cells resistant to NSAIDs in vitro; (iii) these up-regulation protects
      the gastric mucosa from NSAID-induced gastric lesions in vivo. In this review, I
      summarize these results and propose that non-toxic inducers of these stress
      proteins are therapeutically beneficial as anti-ulcer drugs.

PMID- 17450446
TI  - Double balloon endoscopy in two hundred fifty cases for the diagnosis and
      treatment of small intestinal disorders.
AB  - Double balloon endoscopy is based on a new insertion mode in which two balloons
      at the distal ends of both an endoscope and an overtube are operated in
      combination. We have performed 419 enteroscopic examinations in 250 patients
      using the Fujinon double balloon endoscopy system between September 2000 and
      October 2005. Total enteroscopy was successfully achieved by the combination of
      both oral and anal approaches in 55 out of 71 cases in whom total enteroscopy was
      intended. Of 250 patients, ulcerative and/or erosive lesions were found in 49
      cases and tumors/polyps were found in 49 cases. We also found 26 cases of
      vascular lesion, including angiodysplasia. Endoscopic treatments, including
      hemostasis using either clipping devices or electro coagulation, polypectomy,
      endoscopic mucosal resection, balloon dilation, and stent placement was
      successfully carried out. Double balloon enteroscopy is both feasible and useful
      technique for the diagnosis as well as treatment of small intestinal disorders.

PMID- 17450447
TI  - A diagnosis support system for capsule endoscopy.
AB  - The diagnostic time required for a full, 8-hour video capsule endoscopy is
      usually between 45 and 120 min. The aim of this work is to evaluate the
      diagnostic time required when applying a method that adaptively controlls the
      image display rate. The advantage of the method is that the sequence can be
      played at high speed in stable smooth sequences to save time and then decreased
      at sequences where there are sudden rough changes, in order to assess suspicious
      findings detail. In this paper, this method is examined under real conditions: 10
      sequences were independently evaluated by 4 medical doctors. The methods of
      evaluation include: 1) the time required for reading a sequence, 2) the
      percentage of abnormal regions accurately found, and 3) the manipulations of the
      evaluating physicians. The results indicate that the proposed method reduces
      diagnostic time to around 10 +/- 1.5% length of the sequence and is of valuable
      assistance to medical doctors.

PMID- 17450448
TI  - Comparison of gastrointestinal symptoms and psychological factors of functional
      dyspepsia to peptic ulcer or panic disorder patients.
AB  - Symptoms of functional dyspepsia (FD) may look like those of peptic ulcers or
      panic disorders. But, there is no comparative data between the symptoms of peptic
      ulcers or panic disorders. METHODS: To evaluate general symptoms, we used the
      previously validated questionnaires: 1. the Gastrointestinal Symptom Rating Scale
      (GSRS), 2. the Self-Rating Depression Scale (SDS), 3. the State-Trait Anxiety
      Inventory (STAI), and 4. the Coping Inventory for Stressful Situations (CISS).
      Ninety-six patients with FD (ulcer-like, dysmotility-like, and nonspecific: 28.1
      %, 41.7 %, and 30.2 %) diagnosed according to the Rome II criteria, 24 peptic
      ulcer patients, 21 panic disorders, and 50 healthy controls were enrolled in this
      study. RESULTS: Total GSRS score of FD was higher than controls (12.8 +/- 1.2 vs.
      5.9 +/- 0.7), and similar to peptic ulcers. Ratio over than a cut-off SDS score
      of FD was higher than controls (28 % vs. 11 %), although it was lower than panic
      disorders (65 %). Ratios over than cut-off scores of state- and trait-anxiety of
      FD were higher than controls (74 % and 62 % vs. 50 % and 36 %) and tended to be
      higher than peptic ulcers. Positive ratio of state-anxiety scores of FD was
      similar to panic disorders. As these scores increased, morbidity rate of FD
      (FD/FD+control) increased (P for trend <0.01). Among CISS scores, task-oriented
      coping scores of FD tended to be low compared to controls, but emotion-oriented
      coping scores of FD and controls were significantly lower than panic disorders.
      CONCLUSION: Severity of gastrointestinal symptoms but not anxiety of FD was
      similar to peptic ulcers. Psychological scales of FD were also similar to panic
      disorders except for the emotion-oriented coping. These findings suggested that
      the complicated pathogenesis of FD was similar to but not completely consistent
      with peptic ulcers or panic disorders.

PMID- 17450449
TI  - Ecabet sodium prevents esophageal lesions induced by the reflux of gastric juice
      in rats.
AB  - We investigated the effect of ecabet sodium (ecabet) on rat acute esophageal
      lesions induced by reflux of gastric juice. Ligation of both pylorus and fore
      stomach induced the reflux of gastric juice, decreased the amount of mucus and
      formed hemorrhagic lesions in the esophageal mucosa. Intragastric injection of
      ecabet reduced the pepsin activity and prevented both the decrease of mucus
      amount and formation of lesions. Ecabet enhanced the reduction in lesion
      formation induced by omeprazole and ranitidine without a change in decreased acid
      concentration and pepsin activity. Digestion of mucosa and the reduction in mucus
      were prevented by ecabet in the everted HCl and pepsin treated esophageal sac.
      These results indicate that ecabet prevents esophageal lesions by inhibiting
      pepsin activity as well as by protecting mucus from degradation. These further
      implicate the therapeutic potential of ecabet for prevention/treatment of GERD,
      especially in combination with a proton pump inhibitor or H(2)-antagonist.

PMID- 17450450
TI  - Assessment of physical etiologies for mood and anxiety disorders in structured
      diagnostic interviews.
AB  - BACKGROUND: Structured diagnostic inter- views include items that evaluate
      physical etiologies for mood and anxiety disorders. The objective of this article
      was to assess the impact of such items. METHOD: A mental health survey in Canada
      collected data from n = 36,984 household residents. The lifetime prevalence of
      mood and anxiety disorders was calculated with and without exclusions due to
      physical causes. RESULTS: Approximately 10% of subjects with a lifetime
      depressive disorder reported that all of their episodes were due to one or more
      physical cause. Many of the reported etiologies were implausible given the DSM-IV
      requirement that the disturbance be a "direct physiological consequence" of the
      physical cause. The results were similar for manic episodes and anxiety
      disorders. CONCLUSIONS: Structured diagnostic interviews assess physical
      etiologies in ways that are subject to inconsistency and inaccuracy. Physical
      etiology items may bias estimates by introducing etiological opinions into the
      assessment of disorder frequency.

PMID- 17450451
TI  - Trauma, PTSD and the longer-term mental health burden amongst Vietnamese refugees
      : a comparison with the Australian-born population.
AB  - BACKGROUND: Uncertainty persists about the impact of trauma on the long-term
      mental health of resettled refugees. The present study aimed to assess the
      contributions of trauma and PTSD to overall mental disorder and related need for
      services amongst Vietnamese refugees resettled for over a decade in Australia.
      The data were compared with a survey of the host population. METHOD: The study
      involved a probabilistic sample of Vietnamese refugees (n = 1,161) resettled in
      Australia for 11 years. The Australian-born sample (n = 7,961) was drawn from a
      national survey using the same diagnostic measure, the Composite International
      Diagnostic Interview (CIDI). RESULTS: The PTSD prevalence for both groups was
      3.5% and the diagnosis was present in 50% of Vietnamese and 19% of Australians
      with any mental disorder(s). Trauma made the largest contribution to mental
      disorder in the Vietnamese (odds ratio >8), whereas amongst Australians, younger
      age (odds ratio >3) and trauma (odds ratio >4) each played a role. PTSD was
      equally disabling in both populations but Vietnamese with the disorder reported
      more physical, and Australians more mental disability. Approximately one in three
      Australians and one in 10 Vietnamese with PTSD sought help from mental health
      professionals. CONCLUSIONS: Trauma and PTSD continue to affect the mental health
      of Vietnamese refugees even after a decade of resettlement in Australia. The
      tendency of Vietnamese with PTSD to report symptoms of physical disability may
      create obstacles to their obtaining appropriate mental health care.

PMID- 17450452
TI  - Police-registered offenses and psychiatric disorders among young males : the
      Finnish "From a boy to a man" birth cohort study.
AB  - OBJECTIVE: To study associations between crime and psychiatric disorders among
      adolescent males in a representative population-based cohort study. METHOD: The
      sample includes 2,712 Finnish boys born in 1981. Information on criminality
      consists of offenses registered in the Finnish National Police Register 1998
      2001. Crime was classified according to frequency and type (drug, violent,
      property, traffic, and drunk driving offenses). Information on psychiatric
      diagnoses between 1999 and 2004 was collected from the Finnish National Military
      Register. RESULTS: Of the 2,712 boys, 22% had a crime registration during the 4
      year period, and 10% had at least one psychiatric disorder according to the
      Military Register. Those with psychiatric disorders accounted for 49% of all
      crimes. Of those with more than five crimes (n = 98), 59% had psychiatric
      diagnoses. After adjusting for other crime types and childhood socio-economic
      status, property crime was independently associated with several diagnoses:
      antisocial personality (APD), substance use (SUD), psychotic, anxiety, and
      adjustment disorders. Drug offending was independently associated with APD, SUD,
      and psychotic disorder, and traffic offenses with APD. CONCLUSIONS: Youth crime
      is predominantly associated with antisocial personality and substance use
      disorders. Crime prevention efforts should focus on boys showing a risk for
      antisocial and substance use problems. In particular, property, drug, and repeat
      offenders need mental health and substance use assessment. There is a need to
      develop integrated mental health and substance use treatment services for young
      offenders within or alongside the criminal justice system.

PMID- 17450453
TI  - High prevalence of mental disorders and comorbidity in the Geneva Gay Men's
      Health Study.
AB  - BACKGROUND: Several large surveys have suggested high prevalence of psychiatric
      disorders among gay men and other men who have sex with men. METHODS: In 2002, a
      comprehensive health survey was conducted among 571 gay men in Geneva,
      Switzerland, using probability-based time-space sampling. The Composite
      International Diagnostic Interview Short-Form (CIDI-SF) was used to assess 12
      month prevalence of major depression, specific phobia, social phobia, alcohol
      dependence, and drug dependence. RESULTS: Nearly half (43.7%, 95% CI=39.0-48.4)
      of the sample fulfilled the criteria for at least one of the five DSM-IV
      disorders: 19.2% had major depression, 21.9% had specific and/or social phobia,
      and 16.7% had an alcohol and/or drug dependence disorder in the past 12 months.
      Over one quarter of the cases were comorbid with another kind of disorder, and
      35.7% of cases consulted a health care professional in the past 12 months for
      mental health. Like cases, screen-positives for mood and/or anxiety disorders
      (24.7%) also reported significantly greater disability and lower quality of life.
      CONCLUSIONS: Nearly two-thirds of this community sample of gay men was affected
      by psychiatric morbidity with new evidence for comorbidity, subthreshold
      disorders, and low levels of awareness of psychiatric disorders and their
      treatment. This population needs to be a priority in psychiatric epidemiology and
      mental public health.

PMID- 17450454
TI  - Sickness absence and disability pension in a cohort of employees initially on
      long-term sick leave due to psychiatric disorders in Sweden.
AB  - BACKGROUND: Over the last decade sickness absence and disability pension (DP) due
      to psychiatric disorders have increased considerably in Western countries. The
      scientific knowledge base about prognoses for such absences is very limited, but
      employers and clinicians often predict them to be very long. The aim of this
      study was to investigate sickness absence and disability pension in a cohort of
      employees who initially were on long-term sick leave due to psychiatric
      disorders, with regard to gender, age, socioeconomic status, and previous
      sickness absence. METHODS: The cohort included 4,891 employees in Sweden, who, in
      1999 were aged 20-61 and had a new sick-leave spell >90 days with a psychiatric
      disorder. Retrospective and prospective registry data on sickness absence and DP
      for 1996-2002 were obtained. Logistic regressions were performed to estimate odds
      ratios (ORs) with 95% confidence intervals (CIs) for having a low, intermediate,
      or high level of sickness absence (<17, 17-90, and 91-365 days, respectively) or
      DP in 2002. RESULTS: The mean number of sick-leave days per person per year 3
      years prior to inclusion was low; 17 days, but had increased to 211 days by 2000.
      In 2002, 26% had been granted DP, significantly higher rate among men, while a
      higher rate of the women had long-term sickness absence. Of all 4,891 subjects,
      35% had <17 sick-leave days in 2002. The OR of having low, intermediate, or long
      term sickness absence decreased with age. The reverse was found for obtaining DP,
      for which also low socioeconomic status was an independent predictor of an
      increased risk (OR = 3.40, CI 2.28-5.08). CONCLUSIONS: Employees with long-term
      sick leave due to psychiatric disorders did not have a high level of sickness
      absence in the 3 years prior to inclusion in the study. Also, 3 years after
      inclusion, only 35% had very low levels of sickness absence, whereas 26% had been
      granted DP. Employees who were aged 55-61 showed the lowest risk of sick leave
      but the highest risk of DP. Low SES was a significant predictor of DP in 2002.

PMID- 17450455
TI  - Screening for emotional and behavioural problems amongst 5-11-year-old school
      children in Karachi, Pakistan.
AB  - BACKGROUND: While a number of studies in the western countries have provided
      estimates of prevalence for child psychiatric morbidity and associated risk
      factors, relatively little is known about child psychiatric problems and risk
      factors in developing countries like Pakistan. METHOD: A cross sectional survey
      of 5-11-year-old children attending main stream private and community schools in
      Karachi was conducted. Seven private and eight community schools agreed to
      participate. About 1488 consent forms were sent to 700 parents of private school
      and 788 parents of community school children. A total of 675 parents agreed to
      participate in the study. The response rate was 45.4%. Assessment of children's
      mental health was conducted using Strength and difficulties questionnaire (SDQ)
      by parents based on cut-off provided by Goodman. RESULTS: About 47% children were
      rated as normal, 19% as borderline and 34% as abnormal by the parents. Ordinal
      regression was used to identify factors associated with parent's rating. The odds
      of female children of being normal was 1.5 times relative to male children,
      adjusting for school type and mother's education (ORadj = 1.5, 95% CI: 1.1-2.0).
      Children attending private schools were more likely to be normal as compared to
      community school children, adjusting for child's gender and mother's education
      (ORadj = 2.3, 95% CI: 1.3-4.0). CONCLUSION: In the present study, prevalence of
      child mental health problems was higher than reported in studies from other
      countries. Prevalence was higher amongst children attending community schools.
      Consistent with most studies, male children were at a higher risk than females.
      There is a need for developing programs to train, sensitise and mobilize teachers
      and parents regarding child's psychological, emotional and behavioural problems
      with special attention to community schools. Since the male child is at a greater
      risk we should be cognizant of this while evaluating children for
      psychopathology.

PMID- 17450456
TI  - Personality disorder and pathways to inpatient psychiatric care.
AB  - BACKGROUND: The impact of personality disorder on pathways into psychiatric care
      is unknown. AIM: To examine associations between personality disorder status,
      length of pathway into inpatient psychiatric care, and involvement of the
      criminal justice service in the pathway into care. METHOD: The Structured
      Clinical Interview for DSM-IV personality disorders (SCID-II) and a modified WHO
      Pathways Encounter Form were administered to a sample of 153 consecutive
      inpatients admitted to acute wards in one inner London borough over a 4-month
      period. Diagnosis, socio-demographic variables, social support and substance
      misuse were also ascertained. RESULTS: The presence of personality disorder was
      not associated with significant differences in the number of carers, time spent
      along the pathway, or probability of criminal justice system involvement.
      However, all three personality disorder clusters were significantly associated
      with increased use of Accident and Emergency (A & E) services. CONCLUSION: Given
      the high levels of contact with A & E services, casualty staff should receive
      improved training in the assessment and management of patients with personality
      disorders. Improved detection of personality disorder within A & E departments
      could lead to earlier diversion to mental health services and a consequential
      improvement in the planning of subsequent treatment.

PMID- 17450457
TI  - Insomnia and role impairment in the community : results from the Nigerian survey
      of mental health and wellbeing.
AB  - BACKGROUND: Estimates of the occurrence of insomnia are not available in sub
      Sahara Africa where demographic profile is different from that in developed
      countries. However, such estimates need to be considered along with associated
      functional role impairment in assessing the extent of public health burden due to
      insomnia. METHODS: Face-to-face interviews with a representative sample of
      persons aged 18 years and over (n = 6,752) in 21 of Nigeria's 36 states
      (representing about 57% of the national population) was conducted using the
      Composite International Diagnostic Interview, version 3. Role impairment, defined
      as proportion of lost work over the prior month, was assessed using the World
      Health Organization's Disability Assessment Schedule. RESULTS: Insomnia, defined
      as any sleep complaint lasting at least two weeks in the previous 12-months, was
      reported by 11.8%, with rates varying between 5.4% for early morning awakening,
      7.7% for difficulty initiating sleep, and 8.5% for difficulty maintaining sleep.
      Increasing age was associated with higher rates of every type of insomnia but
      females were only more likely than males to report difficulty initiating sleep.
      Independently, chronic pain conditions, chronic medical conditions, as well as
      the presence of a DSM-IV mental disorder significantly increased the risk of
      having insomnia. Multivariate analysis suggests that, even though demographic
      factors and comorbid physical and mental conditions partly accounted for the
      association of insomnia with role impairment, a decrement of about 6% of
      estimated lost work in the prior month was probably attributable to insomnia.
      CONCLUSIONS: Findings indicate that insomnia is common even in this relatively
      young population. Its negative effect on role functioning is considerable, is not
      entirely accounted for by comorbid medical and mental conditions, and may be of
      public health significance.

PMID- 17450458
TI  - A carbon nanotube/silica sol-gel architecture for immobilization of horseradish
      peroxidase for electrochemical biosensor.
AB  - A novel third-generation biosensor for hydrogen peroxide (H202) has been
      constructed based on horseradish peroxidase (HRP) immobilized by the sol-gel (SG)
      technology on carbon nanotube (CNT)-modified electrode. CNT has good promotion
      effects on the direct electron transfer between HRP and the electrode surface and
      the SG network provides a biocompatible microenvironment for enzyme. The
      immobilized HRP retained its bioelectrocatalytic activity for the reduction of
      hydrogen peroxide and can respond to the change of concentration of H2O2 rapidly.
      The heterogeneous electron transfer rate constant was evaluated to be 2.8 +/- 0.4
      s(-1). The amperometric response to H2O2 shows a linear relation in the range
      from 0.5 to 300 micromol 1(-1) and a detection limit of 0.1 micromol 1(-1) (S/N =
      3). The KMapp value of HRP immobilized on the electrode surface was found to be
      1.35 mmol 1(-1). The biosensor exhibited high sensitivity, rapid response and
      excellent long-term stability.

PMID- 17450459
TI  - Individual and combined effects of physicochemical parameters on ellagitannin
      acyl hydrolase and ellagic acid production from ellagitannin by Aspergillus
      oryzae.
AB  - The individual and interactive effects of physicochemical parameters on
      ellagitannin acyl hydrolase activity and ellagic acid production by Aspergillus
      oryzae using ellagitannins from acorn fringe of oak as substrate were studied.
      Ellagitannins concentration, incubation time were identified as important
      physicochemical parameters influencing the enzyme synthesis and the production
      accumulation, and the substrate concentration with initial pH was determined to
      has an interactive effect on the enzyme synthesis, while ellagitannins
      concentration and initial pH with incubation time were found to have interactions
      on the production accumulation. Furthermore, the parameters were optimized by
      quadratic programming. Under optimum condition, the fermentation run lasted 84 h
      with 4 g L(-1) ellagitannins concentration, yielding 17.7% ellagic acid. However,
      the maximum enzyme activity was obtained in 96 h with 5 g L(-1) substrate
      concentration. The research demonstrated a possible way to develop an efficient
      approach for recovery of higher added-value product (ellagic acid) from forestry
      byproduct (acorn fringe of oak).

PMID- 17450461
TI  - Prenatal diagnosis and early treatment of fetal goitrous hypothyroidism and
      treatment results with two-year follow-up.

PMID- 17450460
TI  - Desmids and biofilms of freshwater wetlands: development and microarchitecture.
AB  - Freshwater wetlands constitute important ecosystems, and their benthic, attached
      microbial communities, including biofilms, represent key habitats that contribute
      to primary productivity, nutrient cycling, and substrate stabilization. In many
      wetland biofilms, algae constitute significant parts of the microbial population,
      yet little is known about their activities in these communities. An analysis of
      wetland biofilms from the Adirondack region of New York (USA) was performed with
      special emphasis on desmids, a group of evolutionarily advanced green algae
      commonly found in these habitats. Desmids constituted as much as 23.7% of the
      total algal and cyanobacterial flora of the biofilms during the July and August
      study periods. These algae represented some of the first eukaryotes to colonize
      new substrates, and during July their numbers correlated with fluctuations in
      general biofilm parameters such as biofilm thickness and dry weight as well as
      total carbohydrate. Significant numbers of bacteria were associated with both the
      EPS sheaths and cell wall surfaces of the desmids. Colonization of new substrates
      and development of biofilms were rapid and were followed by various fluctuations
      in microbial community structure over the short- and long-term observations. In
      addition to desmids, diatoms, filamentous green algae and transient non-motile
      phases of flagellates represented the photosynthetic eukaryotes of these
      biofilms.

PMID- 17450462
TI  - Transfusion-associated graft-versus-host disease in a newborn.

PMID- 17450463
TI  - Advances in the treatment of patients with gastric adenocarcinoma.
AB  - Despite a decline in its incidence in the Western world, gastric cancer (GC)
      remains the fourth most frequent cancer diagnosis worldwide and is, after lung
      cancer, the second leading cause of death from a malignant disease globally.
      Based on the published literature, treatment guidelines and reports from
      international meetings, we here review the current treatment options for GC and
      discuss insights and perspectives from the latest clinical studies. The
      management of GC in the early stages of the disease is based on an optimal
      surgical resection of the primary tumor and the regional lymph nodes. However,
      less than one third of patients have a resectable disease at diagnosis and among
      those operated, more than half are not cured by surgery alone, due to a high rate
      of relapse. Thus, for the majority of patients, systemic cytotoxic therapy, and
      sometimes radiotherapy, is a treatment option both as an adjunct to surgery and
      in the palliative setting. Adjuvant chemotherapy offers only a marginal benefit
      and has not become a standard of care in the West. In North America, adjuvant
      chemoradiation is broadly used, shown to significantly improve overall survival,
      albeit with the cost of high toxicity. Furthermore, a recently reported study
      from the United Kingdom demonstrated a significant disease-free and survival
      benefit by the use of perioperative combination chemotherapy. Several
      chemotherapeutic agents have been tested as a palliative therapy in advanced GC
      including 5- fluorouracil (5-FU), oral pyrimidines, platinum derivatives,
      anthracyclines, taxanes and camptothecans. It is now accepted that chemotherapy
      is better than best supportive care only and that 5-FU based combinations are
      more effective than monotherapy. However, the response rates have generally been
      moderate and there is no consensus on the optimal combination of cytotoxic agents
      and the potential role of more recently developed "targeted therapies".

PMID- 17450464
TI  - Nordic biological specimen banks as basis for studies of cancer causes and
      control--more than 2 million sample donors, 25 million person years and 100,000
      prospective cancers.
AB  - The Nordic countries have a long tradition of large-scale biobanking and
      comprehensive, population-based health data registries linkable on unique
      personal identifiers, enabling follow-up studies spanning many decades. Joint
      Nordic biobank-based studies provide unique opportunities for longitudinal
      molecular epidemiological research. The purpose of the present paper is to
      describe the possibilities for such joint studies, by describing some of the
      major Nordic biobank cohorts with a standardised calculation of the cancer
      incidence in these cohorts. Altogether two million donors have since 1966 donated
      more than four million biological samples, stored at -20 degrees C to -135
      degrees C, to 17 biobank cohorts in Finland, Iceland, Norway and Sweden. As a
      result of joint database handling principles, the accuracy of personal
      identifiers and completeness of follow-up for vital status in all participating
      biobanks was improved. Thereafter, the cancer incidence was determined using
      follow-up through the national cancer registries. Biobanks based on random
      samples of population typically showed slightly lower cancer incidence rates than
      the general population, presumably due to better participation rates among health
      conscious subjects. On the other hand, biobanks including samples for viral
      screening or clinical testing showed 1.5 to 2.1 fold increased incidence of
      cancer. This excess was very high immediately after sampling, but for some cancer
      sites remained elevated for years after clinical sampling. So far, more than 100
      000 malignant neoplasms have occurred after sample donation, and the annual
      increase of the cancer cases in these cohorts is about 10 000. The estimates on
      the population-representativity of the biobanks will assist in interpretation of
      generalizability of results of future studies based on these samples, and the
      systematic tabulations of numbers of cancer cases will serve in study power
      estimations. The present paper summarizes optimal study designs of biobank-based
      studies of cancer.

PMID- 17450465
TI  - Short and long-term survival from gastric cancer. A population-based study from a
      county hospital during 25 years.
AB  - The aim of this study was to evaluate the outcome for gastric cancer patients
      treated at a medium sized Norwegian hospital. The medical journals of all 356
      patients with gastric cancer treated at Levanger Hospital from 1980 to 2004 were
      retrospectively analysed. Follow-up with regard to survival was complete. The
      Department of Surgery had treated 277 patients (78%). The resection rate of
      patients admitted to the Department of Surgery was 56% (154/277), and the total
      resection rate was 43% (154/356). R0 resection was done in 97 patients (27%), R1
      resection in 16 (4%), palliative R2 resection in 41 (12%), other palliative
      procedures in 59 (17%), and only palliative care was given for 143 (40%)
      patients. The 30-days postoperative mortality was 2.7% (3/113) after R0 and R1
      resections, 4.9% (2/41) after R2 resections, and 24% (14/59) after other
      palliative procedures. After R0 resections, the estimated overall 5-year survival
      was 39% (95% C.I. 29-49). After R1 and R2 resections, none survived 5 years and
      the estimated overall 2-year survival was 12% (95% C.I. 0-27%) and 2% (95% C.I. 0
      7%), respectively. Estimated overall 5-year survival was closely related to
      stage: 91% (95% C.I. 74-100) in stage 1A, 64% (95% C.I. 53-74) in stage 1B, 27%
      (95% C.I. 10-44) in stage II, 18% (95% C.I. 4-32) in stage IIIA, and none in
      stages IIIB and IV. Dysphagia, fatigue, weight loss, palpable tumour, ascites and
      anaemia were related to a bad prognosis. Dyspepsia, vomiting and hematemesis were
      not related to the prognosis. Symptoms duration > 6 months were related to a
      better prognosis than short duration of symptoms < 2 months. The results from
      this hospital are in accordance with previous reports from the Western world.

PMID- 17450466
TI  - Humoral immune response to MUC1 and to the Thomsen-Friedenreich (TF) glycotope in
      patients with gastric cancer: relation to survival.
AB  - Humoral immune responses to the MUC1 peptide and to MUC1-related Thomsen
      Friedenreich (TF) glycotope was investigated in patients with gastric cancer (n =
      247), chronic gastroduodenal diseases (n = 199) and in healthy blood donors (n =
      100). Data were correlated with disease type, stage of cancer, tumor morphology
      and survival. MUC1 IgG antibody levels were higher in patients with gastric
      cancer (p < 0.0001) than in healthy controls. Higher levels of anti-MUC1 IgG were
      also detected in patients with ulcer of the stomach (p = 0.015) and in atrophic
      gastritis (p = 0.027). Compared to blood donors, significantly lower levels of
      anti-TF IgG were found both in the cancer (p = 0.002) and in the benign group (p
      < 0.0001). At early stages of cancer a positive correlation (p < 0.0001) was
      found between MUC1 IgG and TF IgG antibody levels. High levels of TF IgG
      antibodies were significantly associated with a benefit in survival of gastric
      cancer patients (p = 0.003). A similar though weaker association was observed for
      patients with high levels of MUC1 IgG antibodies and locoregional disease (stage
      I-III) (p = 0.037). Thus IgG immune responses to MUC1 are increased in patients
      with gastric cancer. High levels of either TF IgG or MUC1 IgG antibodies may
      predict better outcome in surgically treated patients with gastric cancer.

PMID- 17450467
TI  - Phase II study of cisplatin, epirubicin, UFT, and leucovorin (PELUF) as first
      line chemotherapy in metastatic gastric cancer.
AB  - More than two-thirds of patients with gastric cancer present with metastatic
      disease and their curative options are limited. This phase II study assessed the
      efficacy and tolerability of cisplatin, epirubicin, tegafur-uracil (UFT) and
      leucovorin in patients with metastatic gastric cancer (MGC). Thirty-nine patients
      with previously untreated metastatic or unresectable gastric cancer received
      intravenous cisplatin 60 mg/m2 and epirubicin 50 mg/m2 on day 1 of a 28-day
      cycle; UFT 300 mg/m2 was administered with oral leucovorin 30 mg/day in divided
      doses on days 1-22, followed by a 7-day rest. Two patients achieved a complete
      response, 13 had a partial response (overall response rate 38%; 95% confidence
      interval [CI] 24-52%) and 16 patients (41%) had stable disease. Median time to
      progression was 6.5 months (95% CI 5.5-7.5 months); overall survival was 9.5
      months (95% CI 8.5-13.5 months). Grade 3/4 neutropenia, anemia, and
      thrombocytopenia occurred in 20%, 8%, and 3% of patients, respectively; two
      patients experienced febrile neutropenia. Grade 3 diarrhea occurred in three
      patients. The combination of cisplatin, epirubicin, UFT, and leucovorin has
      significant activity and tolerable toxicities in patients with MGC and represents
      a convenient treatment option for these patients.

PMID- 17450468
TI  - Phase I study of short-time oxaliplatin, capecitabine and epirubicin (EXE) as
      first line therapy in patients with non-resectable gastric cancer.
AB  - A phase I trial of short-time oxaliplatin (E), capecitabine (X) and epirubicin
      (E) for patients with metastatic gastric cancer was initiated to establish the
      recommended dose for further therapy with short-time EXE. Patients received out
      patient therapy with a fixed dose of epirubicin 50 mg/m2 day 1; escalating doses
      of capecitabine (1,000 to 1,250 mg/m2/day continuously) and escalating doses of
      oxaliplatin (85 to 130 mg/m2 day 1 as a 30 minutes infusion). Cycles were
      repeated every 21 days for a maximum of 8 cycles. From June 2003 to June 2004, 31
      patients were treated. Median age was 61 years (39-75 years), and median
      performance status was 0 (0-2). At level 3, one of six patients developed DLT and
      at dose level 4, two of six patients developed DLT (both patients had grade 4
      hematological toxicities) and thus further dose escalation was not attempted.
      Median number of cycles was 6 (1-8), median survival was 9.2 months and median
      TTP was 7.5 months. A combination of epirubicin 50 mg/m2 day 1, capecitabine
      1,000 mg/m2 continuously and oxaliplatin 130 mg/m2 day 1 each 3 weeks is an
      easily administered and well tolerated out-patient regimen for patients with non
      resectable gastric cancer.

PMID- 17450469
TI  - A phase II study of oxaliplatin with low dose leucovorin and bolus and continuous
      infusion 5-fluorouracil (modified FOLFOX-4) as first line therapy for patients
      with advanced gastric cancer.
AB  - To determine the activity and toxicities of a low dose leucovorin (ldLV) plus
      fluorouracil (5-FU) regimen, combined with oxaliplatin administered fortnightly
      (modified FOLFOX-4), as a first-line therapy for patients with advanced gastric
      cancer. Patients were treated with cycles of oxaliplatin 85 mg/m2 on day 1 plus
      LV 20 mg/m2, followed by 5-FU a 400 mg/m2 bolus and a 22 hour continuous infusion
      of 600 mg/m2 5-FU on days 1 - 2 every two week intervals. Forty-five patients
      were enrolled in this study. Forty-two patients were assessable for response. One
      of the 42 patients demonstrated complete response, and 20 partial responses, and
      overall response rate of 50%. The median time to progression and overall survival
      time were 7.7 months (95% CI: 3.6 - 11.9 months) and 11.2 months (95% CI: 9.1 -
      13.3 months), respectively. Major hematologic toxicities included grade 1 - 2
      anemia (39.7%), neutropenia (30.4%) and grade 3 - 4 neutropenia (10.9%). Twelve
      cycles were associated with neutropenic fever. The most common non-hematological
      toxicities were grade 2 nausea/vomiting (20%). There was no treatment related
      death. The modified FOLFOX-4 regimen was found to be a safe and effective first
      line therapy in advanced gastric cancer.

PMID- 17450470
TI  - Diet and vitamin or mineral supplementation and risk of rectal cancer in Canada.
AB  - The study examines the relation of diet and vitamin or mineral supplementation
      with risk of rectal cancer. Mailed questionnaires were completed by 1 380 newly
      diagnosed patients with histologically confirmed rectal cancer and 3 097
      population controls between 1994 and 1997 in seven Canadian provinces.
      Measurement included information on socio-economic status, lifestyle, diet and
      vitamin or mineral supplementation. We derived odds ratios and 95% confidence
      intervals through unconditional logistic regression. Total of consumption of
      vegetables, fruit and whole-grain products did not reduce the risk of rectal
      cancer. Consumption of cruciferous vegetables was inversely associated with risk
      of rectal cancer among women only, as did chicken intake among men. The strongest
      dietary association with increased rectal cancer risk appeared in males with
      increasing total fat intake and in females with bacon intake. Vitamin and mineral
      supplementation showed significant inverse associations with rectal cancer in
      women only. These findings suggest that dietary risk factors for rectal cancer in
      women may differ from those in men.

PMID- 17450471
TI  - Influence of long-term colonoscopic surveillance on incidence of colorectal
      cancer and death from the disease in patients with precursors (adenomas).
AB  - Case-control studies and short term prospective studies have suggested that
      selected groups of patients with precursors of colorectal cancer may benefit from
      colonoscopic surveillance after initial removal of adenomas. The aim of the
      present study was to demonstrate such a possible benefit from long term (1-24
      years) colonoscopic surveillance in a population of patients with all types of
      adenomas regardless of size and way of removal. Two thousand and forty-one
      patients with a first time diagnosis of colorectal adenoma were included in
      prospective surveillance between year 1978 and 2002. All adenomas were
      considered. Incidence of CRC and mortality from CRC was calculated, using age,
      sex, and calendar specific number of person years of follow-up for comparison
      with the standard Danish population. CRC was found in 27 patients, the expected
      number being 41 (RR 0.65, 95% CI 0.43-0.95). Three of the 27 patients died from
      CRC, the expected number being 25 (RR 0.12, 95% CI 0.03-0.36). A total of 6 289
      colonoscopies resulted in severe complications in 20 patients and two died from
      complications. Long-term colonoscopic surveillance may reduce incidence of CRC as
      well as mortality in patients with sporadic adenomas. The benefit is reduced to a
      minor degree by complications from surveillance.

PMID- 17450472
TI  - CYP450 polymorphisms predict clinic outcomes to vinorelbine-based chemotherapy in
      patients with non-small-cell lung cancer.
AB  - CYP2C19*2(G681A), CYP2C19*3(G636A), CYP2D6*4(C188T), CYP2D6*2(C2938T, G4268C),
      CYP3AP1*3- G44A and CYP3A5*3(A22893G) are the most common polymorphisms detected
      among Chinese that may influence the efficacy of vinorelbine-based therapies to
      treat non-small-cell lung cancer (NSCLC). We detected the genotypes of these
      polymorphisms by PCR-RFLP in 59 patients with NSCLC and assessed their responses
      to vinorelbine. CYP2D6*4(C188T), CYP3AP1*3 (G -44 A) and CYP3A5*3 were found to
      be associated with response to vinorelbine. For the 2D6*4 polymorphism, the 18 of
      32 (56.25%) patients with homozygous (C/C) responded to this therapy, while 6 of
      27 (22.22%) of those heterozygous (C/T) at this site responded. (chi2=5.68, p <
      0.05) For the 3AP1*1/*3 polymorphism, 12 of 42 (28.57%) patients with homozygous
      (A/A) responded, while 12 of 17 (70.59%) with heterozygous (A/G) and homozygous
      (G/G) responded (chi2=7.19, p < 0.01). CYP3A5*3 polymorphism has a result
      corresponding to 3AP1*3 polymorphism. Other polymorphisms were not associated
      with response to vinorelbine. No significant difference in toxicity and survival
      was observed according to SNP genotype.

PMID- 17450473
TI  - Measurement and impact of co-morbidity in elderly patients with advanced non
      small cell lung cancer treated with chemotherapy. A phase II study of weekly
      paclitaxel.
AB  - BACKGROUND: Aging is associated with an increasing of comorbidity and at the time
      of lung cancer diagnosis patients present one or more other serious disease. The
      aim of the study is to evaluate tolerability, response and survival of weekly
      paclitaxel in elderly patients with advanced NSCLC and concomitant diseases.
      METHODS: Patients with advanced NSCLC who were poor candidates to platinum-based
      therapy because of age >65 years and coexistent illnesses received weekly
      paclitaxel over 1 hour at a dose of 80 mg/m2. Comorbidity was evaluated according
      to the Charlson scale, Kaplan-Feinstein index and the Cumulative Illness Rating
      Scale. RESULTS: A total of 57 patients (median age, 74 years; range, 65-84) were
      included. The overall response rate was 44%. Median survival was 7.8 months.
      Grade 3-4 toxicity was uncommon: neutropenia 1.8%, thrombocytopenia 1.8%,
      neuropathy 7%, hypersensitivity reaction 1.8%. Comorbidity indexes were useful to
      characterize better the population of elderly patients, but did not define a
      subgroup with worse prognosis. CONCLUSIONS: The low toxicity profile and efficacy
      of low-dose weekly paclitaxel justified its usage in this group of poor prognosis
      elderly patients with advanced NSCLC and comorbidities. A comorbidity index
      should be introduced in prospective oncological studies in the elderly to ensure
      compatibility.

PMID- 17450474
TI  - A phase II study using vinorelbine and continuous 5-fluorouracil in patients with
      advanced head and neck cancer.
AB  - Seventy patients with advanced head and neck cancer were treated with vinorelbine
      and continuous 5-FU administered in a central venous catheter. Over all response
      was 36% with 9% complete responses. The most common grade 3 and 4 toxicities were
      stomatitis (13), infection (5), pain related to vinorelbine infusion (4), skin
      toxicity (3). Thirty one patients had grade 3 or 4 leukopenia. Treatment was
      complicated by venous thrombosis in the central venous catheter in one case. A
      majority of patients experienced dose reduction of one or both drugs or treatment
      delays due to toxicity. Median time to progression was 4.7 months and overall
      median survival 6.6 months. We conclude that the regimen is feasible and
      tolerated with moderate toxicity. Response rates and time to progression are
      comparable to other studies with multi agent treatment.

PMID- 17450475
TI  - Methionine aminopeptidase 2 over-expressed in cholangiocarcinoma: potential for
      drug target.
AB  - Methionine aminopeptidases (MetAP) are proteases which remove the N-terminal
      methionine from newly synthesized proteins. Associations of MetAP2 with tumor
      progression of different cancers have been repeatedly reported. We aim to
      determine if MetAP2 is expressed in cholangiocarcinomas (CCA) and investigate to
      see if it would be a useful therapeutic target. We evaluated MetAP2 expression by
      immunohistochemistry in 82 patients of intrahepatic CCA. MetAP2 was expressed in
      bile ducts to various degrees. It was occasionally expressed with weak staining
      in normal bile duct epithelium but was strikingly over-expressed in dysplastic
      bile duct epithelia, primary and metastatic CCA tissues (p < 0.001). The
      increased expression of MetAP2 in proliferating bile duct was evident. All
      metastatic tumors had stronger expression of MetAP2 than the corresponding
      primary tumors. Fumagillin, a MetAP2 specific inhibitor, significantly inhibited
      cell proliferation in dose dependent manner and the degree of growth inhibition
      was dependent on the amount of cellular enzyme. The present study highlights the
      involvement of MetAP2 in an early event of carcinogenesis of CCA. The findings
      represent the first description of increased MetAP2 expression in CCA. The
      inhibition of enzyme activity using MetAP2 inhibitors may be a potential strategy
      for long-term control of tumor development and progression in CCA patients.

PMID- 17450476
TI  - Volumetric staging (VS) is superior to TNM and AJCC staging in predicting outcome
      of head and neck cancer treated with IMRT.
AB  - The UICC classification (TNM) represents the validated standard tool to describe
      tumor extent and includes prognostic information on the probability of disease
      control. The American Joint Committee on Cancer (AJCC) stage grouping is based on
      the evaluation of treatment and outcome. Gross tumor volume (GTV) might be more
      relevant than pure description (TNM) or stage grouping as prognostic factor for
      local control in head and neck cancer (HNC). Based on the observation of GTV
      correlated outcome in our initial HNC patient cohort treated with IMRT, we tested
      the hypothesis that the GTV is the most reliable predictive tool in HNC outcome.
      A GTV based volumetric staging system (VS) was introduced, using two volumetric
      cut-off values (15 and 70 cm3). VS, TNM, and AJCC stages were assessed and
      correlated with outcome following primary radiation in 172 HNC patients. Analyses
      were based on Kaplan-Meier survival curves. VS proved to be superior to the
      TNM/AJCC in predicting outcome. In addition, VS enabled to stratify high- and low
      risk patients in advanced TN stages. GTV represented the most important
      prognostic indicator in HNC treated with IMRT and is recommended to be considered
      for therapeutic decisions and estimation of outcome.

PMID- 17450477
TI  - Fractionation sensitivity and equivalent doses. Commenting on the editorial by
      Glimelius.

PMID- 17450479
TI  - Efficacy and safety of cisplatin and capecitabine in combination as first line
      treatment for unselected patients with advanced gastric cancer.

PMID- 17450487
TI  - What is the best first choice treatment option for Helicobacter pylori?

PMID- 17450488
TI  - Gastrointestinal food hypersensitivity: symptoms, diagnosis and provocation
      tests.
AB  - As many as 25% of the general population in Western countries believe that they
      suffer from adverse reactions to food. However, the actual prevalence of food
      allergy is much lower. Food-induced allergic reactions cause a variety of
      symptoms including cutaneous, gastrointestinal and respiratory tract. Food
      allergy might be caused by IgE-mediated, mixed (IgE and/or non-IgE) or non-IgE
      mediated (cellular) mechanisms. The clinical diagnosis is based on a careful
      history, laboratory findings (total and specific IgE), skin prick test,
      elimination diet and food challenges. New intestinal provocation tests have also
      been applied to pick up the allergic response of the duodenal mucosa by
      endosonography and external ultrasound. The management of food allergy continues
      to be a strict avoidance of the offending food item.

PMID- 17450489
TI  - Overlap of symptoms of dyspepsia and gastroesophageal reflux in the community.
AB  - BACKGROUND/AIMS: Dyspepsia and gastroesophageal reflux disease are common chronic
      diseases. In the clinical setting, some patients express both problems together;
      however, little is known about the real prevalence of the presence of the two
      symptoms. Turkey is particularly interesting because of differences observed from
      developed countries. We aimed to derive data from our previous prevalence of
      gastroesophageal reflux disease study and evaluate the overlap of the two
      symptoms. METHODS: We used a previously validated and culturally adapted reflux
      questionnaire, which was translated into Turkish. The questionnaire was applied
      to 630 randomly selected subjects older than 20 years living in a population of
      8857 adults. RESULTS: 28.6% (180/630) of all responders defined dyspepsia within
      the last 12-month period. When symptom prevalence was considered at least weekly,
      the prevalence was 10% for heartburn, 15.6% for acid regurgitation, and 20% for
      either symptom. While the prevalence of gastroesophageal reflux disease was 29.4%
      in patients with dyspepsia, dyspepsia was found in 43.1% of patients with
      gastroesophageal reflux disease. Only 21% of symptomatic subjects or 8.4% of the
      entire study population had both symptoms. Dyspepsia was defined as the most
      bothersome symptom. 54.3% of all dyspeptic patients and 67.3% with both
      gastroesophageal reflux disease and dyspepsia used a gastric medication (p>0.05).
      29.9% of subjects with dyspeptic symptoms defined antacid consumption and 28.3%
      acid inhibitor therapy. CONCLUSION: Dyspepsia was defined as the most bothersome
      symptom compared to gastroesophageal reflux disease symptoms. The prevalence of
      dyspepsia in patients with gastroesophageal reflux disease is more common than
      vice versa. However, the overlap of the two symptom groups was lower than
      expected in this low-income, Caucasian population.

PMID- 17450490
TI  - Hepatitis B/C virus co-infection in Iran: a seroepidemiological study.
AB  - BACKGROUND/AIMS: As hepatitis B and C virus have the same transmission routes,
      dual infection may occur. The aim of this study was to determine the
      seroprevalence of HCV in HBsAg-positive subjects. METHODS: 139 HBsAg-positive
      subjects were enrolled in the study. Serum samples were tested using ELISA method
      for anti-HCV antibodies. Chi-square and Fisher's exact tests were used to compare
      the proportions. RESULTS: There were 68 (48.9%) males and 71 (51.1%) females. The
      mean age was 41.89+/-11.30 years. One case was excluded because of inadequate
      blood sampling. Anti-HCV antibody was positive in 17 (12.3%) of the 138 remaining
      subjects. Seropositivity of HCV was similar between female and male patients
      (p=0.69). CONCLUSION: The seroprevalence of co-infection with hepatitis B virus
      and hepatitis C virus in our study was higher than such reports from some
      countries (Italy), but was in line with worldwide prevalence (>10%).

PMID- 17450491
TI  - Cystic echinococcosis in Central Saudi Arabia: a 5-year experience.
AB  - BACKGROUND/AIMS: In this series of patients we aim to describe aspects of
      presentation, diagnosis and management of patients suffering from Echinococcosis
      in an endemic region. METHODS: This is an observational study done at Riyadh
      Medical Complex, Saudi Arabia from 1999 to 2004. All adult patients admitted with
      the primary or incidental diagnosis of echinococcosis were included. These
      patients were followed up for 6 months. Data relating to patients' demographic
      characteristics, mode and duration of presentation, investigations, complications
      and treatment offered was collected. This data was then analyzed using SPSS 11.0.
      RESULT: 117 patients with a mean age of 40.9+/-20.7 years were admitted, male to
      female ratio being 1.7:1. 114 (97.4%) originated from Middle East which is an
      endemic area. Pain right upper quadrant (RUQ), followed by cough were the
      commonest symptoms. Nine patients presented with jaundice +/- choleangitis: 3
      patients had intrabiliary rupture of the hydatid cyst, while 6 had extrinsic
      compression. Six patients had infected cyst. Fourteen patients had intrabronchial
      rupture diagnosed on bronchoscopy. Twenty five (21.4%) patients presented with
      recurrent disease. The Haemagglutination Inhibition test gave a sensitivity of
      78.6. All cysts were visualized using USG, CXR and CT scan. Endocystectomy was
      the most frequent procedure. Post op 8 patients had biliary leakage and 3 had
      bronchopleural fistula a majority of whom settled conservatively while two
      required ERCP and one patient with bronchopleural fistula required surgery.
      Fifteen patients had infection related complications. During our follow up period
      no recurrences were recorded. All patients undergoing surgery also received
      medical treatment. Twenty five patients (21.4%) were unable to undergo operative
      treatment due to multiple reasons. They were medically treated. CONCLUSION:
      Cystic Echinococcosis is a disease of the middle aged. Ultrasonogram combined
      with a serological assay is the best diagnostic tool available for abdominal
      echinococcosis allowing diagnosis and staging, while chest X ray is the best
      screen for the pulmonary disease. The recommended treatment is endocystectomy
      with antihelmenthic therapy. But the problem of early detection of echinococcosis
      in endemic areas needs attention by workers as this approach can potentially
      prevent the devastating complications due to this disease.

PMID- 17450492
TI  - Hepatolithiasis: a Turkey experience.
AB  - BACKGROUND/AIMS: The aim of this study was to report our experience of
      hepatolithiasis, diagnosed in 55 patients between June 1995 and March 2003.
      METHODS: Fifty-five patients who underwent endoscopic retrograde
      cholangiopancreatography for hepatolithiasis between June 1995 and March 2003 at
      our institution were evaluated. Diagnosis of hepatolithiasis was based on
      cholangiography, ultrasonography and computed tomography. Patients with
      hepatolithiasis were classified according to Tsunoda classification. RESULTS:
      Fifty-five patients with hepatolithiasis (22 female, 33 male; mean age: 48.2 +/
      14.9, range: 22-83) were included in this study. The major causes of
      hepatolithiasis were previous bilio-digestive surgery and Caroli disease, with
      rates of 49% and 14.5%, respectively. While 37 of 55 patients (67.3%) presented
      with only intrahepatic lithiasis, 18 patients (32.7%) had intrahepatic lithiasis
      associated with common bile duct (16/18, 29%) or gallbladder (2/18, 3.6%) stones.
      According to Tsunoda classification, 4 patients were classified as type I, 32
      type II, 9 type III and 10 type IV. Patients with types I and II had
      significantly better stone clearance rates in comparison to those with types III
      and IV (p<0.05). Complete eradication of stones in the patients with proximal
      strictures was significantly lower than in the patients with distal strictures
      (p<0.01). While complete clearance of stones was achieved in 22 cases (40%),
      incomplete clearance was achieved in 17 cases (30.9%) with endoscopic retrograde
      cholangiopancreatography . Mean number of endoscopic retrograde
      cholangiopancreatography procedures for clearance of stones was 4 (ranges: 1-9).
      CONCLUSION: The etiology of hepatolithiasis in our patients is similar to that
      observed in Western populations and endoscopic approach appears to be an
      effective alternative to surgery.

PMID- 17450493
TI  - Multidrug resistance of isolated microorganisms in occluded bile duct stents.
AB  - BACKGROUND/AIM: Biliary stents have been used for benign or malignant biliary
      strictures, preoperative biliary drainage, resolution of biliary or pancreatic
      leaks, and dissolution treatment of non-extractable bile duct stones since 1979,
      and should be replaced at 3-6 month intervals. The aim of this cross-sectional
      pioneer study was to identify the microorganisms in occluded bile duct stents and
      to determine incidence and diagnosis of multidrug resistance of the isolated
      microorganisms in stents and in blood cultures. METHODS: Fifty-one patients (14F,
      37M, mean age: 58.2+/-11.6 yr) with cholangitis due to occluded stents were
      studied consecutively and prospectively after stent replacement was done.
      Independent variables were age, gender, underlying disease, duration of disease,
      size, length and period of stents, and blood biochemistry. Dependent variables
      were microorganisms isolated from the stent content and blood of the patients and
      the results of antibiogram tests. RESULTS: Primary disease was malignant in 25
      (49.0%), stent size was 7F in 30 (58.8%), and stent length was 11 cm in 11
      (21.6%) and 15 cm in 12 (23.5%) of the patients. The mean period after the 1st
      stent application was 207.0+/-111.3 days and the last stent duration was 111.0+/
      64.0 days. Isolated microorganisms from stents and blood, respectively, were
      Escherichia coli (E. coli) (43.4%, 20.8%), Klebsiella spp. (17.1%, 17.0%),
      Pseudomonas aeruginosa (P. aeruginosa) (13.2%, 18.9%) and Enterococcus spp.
      (10.5%, 17.0%). Isolated microorganisms showed multidrug resistance at high
      percentages (81.6% for stent, 81.1% for blood). ALT, AST, ALP, and direct
      bilirubin levels showed statistically significant differences between the benign
      and malignant groups. CONCLUSION: All bile duct stents are contaminated by
      microorganisms, of which a high majority has multidrug resistance, and they
      frequently cause biliary sepsis. Biliary sepsis can be prevented by changing the
      stents periodically and by using proper antibiotic prophylaxis.

PMID- 17450494
TI  - Gastric carcinoma during pregnancy: report of a case.
AB  - BACKGROUND/AIMS: Gastric cancer in pregnancy is extremely rare and often
      diagnosed at advanced stages. Well-recognized pregnancy-related symptoms, such as
      nausea and epigastric discomfort, can be the first symptoms of gastric cancer.
      Thus, the diagnosis of gastric cancer in pregnancy is difficult. We herein report
      a case of gastric cancer in pregnancy to alert clinicians to this rare
      possibility. MATERIALS AND METHODS: A 22-year- old nulliparous woman was examined
      by a gynecologist with a complaint of low abdominal pain. An abdominal ultrasound
      of the patient revealed 7th week of gestation and also showed massive ascites.
      She was referred to a hospital for further evaluation. Her other symptoms
      included loss of appetite, early satiety, and postprandial fullness. Gastroscopy
      demonstrated a tumor originating from the cardia and invading throughout the
      distal corpus. The histopathological diagnosis was gastric carcinoma with signet
      ring cells and her pregnancy was terminated. An explorative laparotomy revealed
      an unresectable gastric cancer and multiple peritoneal implants. Tumoral invasion
      was detected in pancreas and spleen. She was admitted to the medical oncology
      clinic and received a palliative chemotherapy. Bilateral double-J-stent placement
      was performed because of obstructive uropathy. A nasogastric tube was inserted
      for intestinal decompression, and total parenteral nutrition was administered. An
      adequate pain medication was given. To date (3 months after the diagnosis) the
      patient has been well without any signs of progression. CONCLUSION: Early
      diagnosis of gastric cancer is very important for a better outcome. The diagnosis
      may be delayed because mild gastrointestinal symptoms are common during
      pregnancy. Clinicians should take this into consideration in the differential
      diagnosis of persistent epigastric complaint during pregnancy. Suspicion and
      early upper gastrointestinal endoscopy are necessary.

PMID- 17450495
TI  - Primary gastric actinomycosis: a case report.
AB  - Gastric actinomycosis is an extremely rare disease. To date, about 20 cases have
      been reported in the literature. In most cases, diagnosis was made by
      histopathologic evaluation of an operative specimen. We report here a 68-year-old
      man with primary gastric actinomycosis who was admitted to the hospital with
      upper gastrointestinal bleeding and diagnosed as actinomycosis by microscopic
      examination of biopsy specimens obtained by endoscopy. This case is reported
      because of the rarity of endoscopically diagnosed primary gastric actinomycosis.

PMID- 17450496
TI  - Coexistence of papillary renal cell carcinoma and gastrointestinal stromal tumor
      in a case.
AB  - Gastrointestinal stromal tumors are rare causes of gastrointestinal bleeding. In
      most cases, these tumors are localized in the stomach and small intestine, more
      rarely in the esophagus and colon. Papillary renal cell carcinoma and
      gastrointestinal stromal tumor may occur as recurrent familial tumors related to
      mutations in the protooncogenes, c-MET and c-KIT, both of which are tyrosine
      kinase receptor molecules. However, these two tumors can sometimes occur
      simultaneously in sporadic cases. Some authors blame imatinib mesylate (Gleevec),
      which is traditionally used in gastrointestinal stromal tumor therapy, as the
      etiological factor in certain secondary tumors, especially papillary renal cell
      cancer. In this paper, we present the appearance and growth of papillary renal
      cell carcinoma in a patient receiving Gleevec therapy for gastrointestinal
      stromal tumor.

PMID- 17450497
TI  - Ileocecal intussusception in an adult: a case report.
AB  - Intussusception is relatively rare in adults and differs from the childhood form
      in its etiology, presentation and treatment. Unlike childhood intussusception,
      adult intussusception is usually due to underlying pathologic lead points, most
      probably neoplasms. The main clinical presentation of intussusception in the
      adult is chronic abdominal pain, and acute adult intussusception is uncommon.
      Here, we describe an uncommon case of acute ileocecal intussusception due to
      ileal lymphoid hyperplasia in a 46-year-old woman. Lymphoid hyperplasia of the
      intestines is a benign reactive process. Intestinal lymphoid hyperplasia has been
      reported in association with infections and as an allergic response to various
      foods. In adults, it has been reported to occur in association with immune
      deficiencies. There were no obvious causes for this patient's ileal lymphoid
      hyperplasia. We conclude that physicians need to consider intussusception, due to
      intestinal lymphoid hyperplasia, as a possible cause of acute abdominal pain in
      adults, even in the absence of any specific medical history.

PMID- 17450498
TI  - Definition of C282Y mutation in a hereditary hemochromatosis family from Turkey.
AB  - Hereditary hemochromatosis is an autosomal recessive disorder associated with the
      mutation of the HFE gene. C282Y and H63D mutations in this gene have been
      described. Hereditary hemochromatosis is primarily associated with the C282Y
      mutation; the importance of H63D is not well known. In previously reported
      studies, the C282Y mutation was not detected in Turkey. We herein present a
      family in which the C282Y mutation was detected. A consanguineous marriage
      produced 10 children. A 33-year-old man (index case) was diagnosed with
      hemochromatosis (transferrin saturation rate 80%, ferritin 514 ng/ml, liver
      biopsy showed +3 iron accumulation, liver involvement in MRI), and genetic
      analysis showed homozygous C282Y mutation. With family screening, another brother
      was also diagnosed with hemochromatosis. Transferrin saturation rate was high
      (>45%) in seven healthy brothers and the father. Genetic analysis revealed two
      cases with C282Y homozygous mutations, three with C282Y/H63D compound
      heterozygous mutations, one C282Y heterozygous and three H63D heterozygous among
      the family members. This is the first family in Turkey in which the C282Y
      mutation has been detected.

PMID- 17450499
TI  - Laparoscopic treatment of pyogenic liver abscess complicating Crohn's disease: a
      case report.
AB  - Pyogenic liver abscess in patients with Crohn's disease is not common, but the
      mortality has been reported to be high if diagnosis or treatment is delayed.
      Herein, we report the case of a 42-year-old man in whom multi-locular liver
      abscess was encountered in the right lobe of the liver as a complication of
      Crohn's disease. On his admission to the emergency unit, he had right upper
      quadrant pain, fever of 39 degrees C and hepatomegaly. Ultrasonography and
      abdominal computerized tomography demonstrated multi-locular pyogenic liver
      abscess in the right lobe of the liver. Percutaneous drainage failed because of
      the density of the pus; laparoscopic exploration was subsequently performed and
      1500 ml pus was successfully drained. The patient became clinically stable
      without fever and with a decreasing white blood cell count on the third
      postoperative day.

PMID- 17450500
TI  - A case of syphilis investigated due to high liver enzymes.

PMID- 17450501
TI  - Individualized treatment rules: generating candidate clinical trials.
AB  - Individualized treatment rules, or rules for altering treatments over time in
      response to changes in individual covariates, are of primary importance in the
      practice of clinical medicine. Several statistical methods aim to estimate the
      rule, termed an optimal dynamic treatment regime, which will result in the best
      expected outcome in a population. In this article, we discuss estimation of an
      alternative type of dynamic regime-the statically optimal treatment rule. History
      adjusted marginal structural models (HA-MSM) estimate individualized treatment
      rules that assign, at each time point, the first action of the future static
      treatment plan that optimizes expected outcome given a patient's covariates.
      However, as we discuss here, HA-MSM-derived rules can depend on the way in which
      treatment was assigned in the data from which the rules were derived. We discuss
      the conditions sufficient for treatment rules identified by HA-MSM to be
      statically optimal, or in other words, to select the optimal future static
      treatment plan at each time point, regardless of the way in which past treatment
      was assigned. The resulting treatment rules form appropriate candidates for
      evaluation using randomized controlled trials. We demonstrate that a history
      adjusted individualized treatment rule is statically optimal if it depends on a
      set of covariates that are sufficient to control for confounding of the effect of
      past treatment history on outcome. Methods and results are illustrated using an
      example drawn from the antiretroviral treatment of patients infected with HIV.
      Specifically, we focus on rules for deciding when to modify the treatment of
      patients infected with resistant virus.

PMID- 17450502
TI  - Anticancer activity of limonoid from Khaya senegalensis.
AB  - Two limonoids were isolated from the methanol extract of Khaya senegalensis
      (Meliaceae), and their structures were identified as 3alpha,7alpha
      dideacetylkhivorin (1) and 1-O-acetylkhayanolide B (2) on the basis of MS and NMR
      spectral data. Complete assignments of (1)H and (13)C chemical shifts for
      compounds 1 and 2 were achieved by means of 1D and 2D NMR including DEPT, (1)H
      (1)H COSY, HMQC, HMBC experiments. Compound 1 showed significant growth
      inhibitory activities against MCF-7, SiHa and Caco-2 cells with IC(50) values in
      the range of 0.07-0.14 microm (35-69 ppm) while compound 2 did not.

PMID- 17450503
TI  - A novel cytotoxic lignan from Seseli annuum L.
AB  - A new tetrahydrofuranoid lignan named seselinone was isolated from the aerial
      parts of Seseli annuum, together with three known lignans (eudesmin, magnone A
      and hernone) and prenylated coumarin umbelliprenin. Seselinone and eudesmin
      showed cytotoxic activity against C6 rat glioma cell cultures.

PMID- 17450504
TI  - In vivo supplementation with Ginkgo biloba protects membranes against lipid
      peroxidation.
AB  - The effect of Ginkgo biloba (Gb) supplementation in vivo was studied on lipid
      peroxidation of microsomal membranes. Administration of up to 100 mg/kg/day Gb to
      rats did not significantly affect either the activity of microsomal enzymes, the
      rate of generation of superoxide anion or the iron reduction rate by rat liver
      microsomes. Lipid peroxidation, assessed by the generation of lipid radicals
      measured by electron paramagnetic resonance (EPR) spectroscopy using POBN as the
      spin trap, was reduced by 39.7% and thiobarbituric acid reactive substances
      (TBARS) generation by 30% after Gb supplementation (100 mg/kg/day) for 10 days.
      Moreover, membranes from Gb treated animals showed a significant lower content of
      lipid radicals and TBARS after exposure to oxidative stress both in vitro (t
      butyl hydroperoxide) and in vivo (acute iron overload). The data presented here
      showed that Gb extracts were able to limit lipid peroxidation and scavenge lipid
      radicals in vivo and actively protect membranes from oxidative damage.

PMID- 17450505
TI  - Effect of essential oils and isolated compounds from Pimpinella species on NF
      kappaB: a target for antiinflammatory therapy.
AB  - Pimpinella essential oils and isolated compounds were screened for their
      inhibitory activity against NF-kappaB mediated transcription in SW1353 cells.
      Twelve oils were effective in inhibiting NF-kappaB mediated transcription.
      Especially the roots of P. corymbosa, P. tragium and P. rhodanta showed potent
      activities with IC(50) values of 2, 3 and 6 microg/mL, respectively. Five pure
      compounds, 7 (4-(2-propenyl)phenylangelate), 12 (4-(3
      methyloxiranyl)phenyltiglate), 17 (4-methoxy-2-(3-methyloxiranyl)phenyl
      isobutyrate), 18 (4-methoxy-2-(3-methyloxiranyl)phenylangelate) and 21 (epoxy
      pseudoisoeugenol-2-methylbutyrate) inhibited NF-kappaB mediated transcription
      with IC(50) values of 5.5, 1.2, 0.01, 3.6 and 11 microg/mL, respectively. None of
      the compounds were cytotoxic to mammalian cells. These findings add significant
      information to the pharmacological activity of Pimpinella species and their
      beneficial effects and use in disease prevention especially those related to
      inflammation.

PMID- 17450506
TI  - Antiinflammatory effects of a combined herbal preparation (RAH13) of
      Phellodendron amurense and Coptis chinensis in animal models of inflammation.
AB  - In an attempt to develop an antiinflammatory herbal remedy that is as potent as
      current synthetic medicines, the cortex of Phellodendron amurense Rupr (Rutaceae)
      and the rhizomes of Coptis chinensis Franch (Ranunculaceae) were combined in a
      2:1 ratio. This ratio was chosen based on in vitro experiments and traditional
      Asian medicine prescriptions. The combined ethanol extract, named RAH13, was
      evaluated for antiinflammatory properties using animal models of acute
      inflammation such as the croton oil-induced ear edema test and an acetic acid
      induced capillary permeability test. Models of chronic inflammation were also
      tested using the cotton pellet test and a delayed-type hypersensitivity (DTH)
      test. Oral administration of RAH13 at a dose of 200 mg/kg showed in vivo
      antiinflammatory activity as potent as the effects associated with 100 mg/mL of
      celecoxib or 1 mg/kg of dexamethasone. These effects were seen in both acute and
      chronic inflammation models, suggesting that RAH13 may be effective in
      controlling some inflammation-related diseases.

PMID- 17450507
TI  - Cardioprotective effects of the combined use of puerarin and Danshensu on acute
      ischemic myocardial injury in rats.
AB  - Ischemic heart diseases are the leading cause of death in both developed and
      developing countries over the past decades. The aim of this study was to
      investigate the cardioprotective effects of the complex preparation (called
      Shenge), made of puerarin and Danshensu, on acute ischemic myocardial injury in
      rats and its underlying mechanisms. The left anterior descending (LAD) coronary
      artery was occluded to induce myocardial ischemia in hearts of SD rats. Shenge
      was injected into the tail vein 15 min after occlusion at doses of 0, 30, 60 or
      120 mg/kg. Then, the ST elevation was measured at 60, 120 and 240 min after
      Shenge administration. The infarct size, serum levels of creatine kinase
      isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and
      malondialdehyde (MDA), and the ST elevation were measured after the rats were
      killed. Shenge decreased the ST elevation induced by acute myocardial ischemia,
      reduced infarct size, serum levels of CK-MB, LDH and MDA and increased the serum
      activity of SOD in a dose-dependent manner. The combined use of puerarin and
      Danshensu at a ratio of 1:1 shows the most effective activity. In conclusion,
      Shenge exerts significant cardioprotective effects against acute ischemic
      myocardial injury in rats, likely through its antioxidant and antilipid
      peroxidation properties, and thus may be used as an effective and promising
      medicine for both prophylaxis and treatment of ischemic heart disease.

PMID- 17450508
TI  - Effect of the aqueous extract of Syzygium cumini on carbon tetrachloride-induced
      hepatotoxicity in rats.
AB  - The aim of this study was to evaluate the effect of the aqueous Syzygium cumini
      leaf extract, given either as a single dose or by 7 days of pretreatment, on
      hepatotoxicity induced by carbon tetrachloride in rats. Blood samples obtained
      after treatments were measured for aspartate aminotransferase (AST) and alanine
      aminotransferase (ALT). A significant increase in the AST and ALT activities
      occurred after carbon tetrachloride administration alone, which was significantly
      lowered by preadministration with the aqueous extract of Syzygium cumini, but not
      by a single dose. This suggests that the extract may be useful for liver
      protection but needs to be given over a significant period and prior to liver
      injury.

PMID- 17450509
TI  - Gedunin, a limonoid from Xylocarpus granatum, inhibits the growth of CaCo-2 colon
      cancer cell line in vitro.
AB  - Xylocarpus granatum J. Konig (Meliaceae), commonly known as 'dhundul', is a
      Bangladeshi mangrove tree, and well distributed in a number of other countries of
      south-east Asia, Australia and east Africa. Traditionally, X. granatum has been
      used as an astringent and febrifuge, and also for the treatment of fever,
      malaria, thrush, cholera, dysentery and diarrhoea in many countries including
      Bangladesh. Two limonoids, gedunin and 1alpha-hydroxy-1,2-dihydrogedunin, the
      latter being new, have been isolated from the bark of Xylocarpus granatum by
      reversed-phase preparative HPLC, and the structures were confirmed by
      spectroscopic means. The cytotoxic potential of gedunin has been evaluated by the
      Promega's CellTiter 96 non-radioactive cell proliferation assay using the CaCo-2
      colon cancer cell line (IC(50) = 16.83 microM). A summary of the biological
      activities of gedunin reported to date is also presented.

PMID- 17450510
TI  - Neurophysiological evidence of methylmercury neurotoxicity.
AB  - BACKGROUND: A variety of neurophysiological measures are useful in hospital
      settings for diagnostic and other clinical purposes. Previously, abnormal changes
      in various sensory evoked potentials (EPs), and heart rate variability (HRV) were
      observed in patients with acquired and fetal Minamata disease (MD; methylmercury
      poisoning). In recent years, some of these methods have been used for the risk
      assessment of low-level methylmercury exposure in asymptomatic children. The
      objectives of this article were to present an overview of neurophysiological
      findings involved in methylmercury neurotoxicity and to examine the usefulness of
      those measures. METHODS: The reports addressing both neurophysiological measures
      and methylmercury exposure in humans were identified and evaluated. RESULTS: The
      neurological signs and symptoms of MD included paresthesias, constriction of
      visual fields, impairment of hearing and speech, mental disturbances, excessive
      sweating, and hypersalivation. Neuropathological lesions involved visual,
      auditory, and post- and pre-central cortex areas. Neurophysiological changes
      involved in methylmercury, as assessed by EPs and HRV, were found to be in
      accordance with both clinical and neuropathological observations in patients with
      MD. CONCLUSIONS: EPs and HRV appear to be useful and objective methods for
      assessing methylmercury neurotoxicity. However, subtle changes due to low-level
      methylmercury exposure may not necessarily be of clinical relevance, and
      interpretation of small deviations from expectations must be cautious.

PMID- 17450511
TI  - Signaling pathways mediating cardiac myocyte gene expression in physiological and
      stress responses.
AB  - The contractile cells in the heart (the cardiac myocytes) are terminally
      differentiated. In response to pathophysiological stresses, cardiac myocytes
      undergo hypertrophic growth or apoptosis, responses associated with the
      development of cardiac pathologies. There has been much effort expended in
      gaining an understanding of the stimuli which promote these responses, and in
      identifying the intracellular signaling pathways which are activated and
      potentially involved. These signaling pathways presumably modulate gene and
      protein expression to elicit the end-stage response. For the regulation of gene
      expression, the signal may traverse the cytoplasm to modulate nuclear-localized
      transcription factors as occurs with the mitogen-activated protein kinase or
      protein kinase B/Akt cascades. Alternatively, the signal may promote
      translocation of transcription factors from the cytoplasm to the nucleus as is
      seen with the calcineurin/NFAT and JAK/STAT systems. We present an overview of
      the principal signaling pathways implicated in the regulation of gene expression
      in cardiac myocyte pathophysiology, and summarize the current understanding of
      these pathways, the transcription factors they regulate and the changes in gene
      expression associated with the development of cardiac pathologies. Finally, we
      discuss how intracellular signaling and gene expression may be integrated to
      elicit the overall change in cellular phenotype.

PMID- 17450512
TI  - Melt-processed polyfluorene nanowires as active waveguides.

PMID- 17450513
TI  - Towards nanoporous membranes based on ABC triblock terpolymers.
AB  - Block copolymers represent an exciting class of complex materials as they self
      assemble into highly regular structures of nanoscopic dimensions. When prepared
      as thin films, such structures can be used for a variety of applications
      including lithographic masks or nanoporous membranes. Reported here are
      nanostructures in thin films of structurally analogous polybutadiene-block-poly(2
      vinyl pyridine)-block-poly(tert-butyl methacrylate) (BVT) and polystyrene-block
      poly(2-vinyl pyridine)-block-poly(tert-butyl methacrylate) (SVT) triblock
      terpolymers, which are synthesized via sequential living anionic polymerization.
      The morphological behavior of annealed SVT and BVT films is investigated by
      scanning force and electron microscopies. The difference in the terpolymer
      composition results in the formation of an ordered perforated lamella phase in
      SVT films and hexagonally packed core/shell cylinders in BVT films. Further, the
      BVT films show high potential for the fabrication of composite membranes using
      track-etched poly(ethylene terephthalate) macroporous filters as a support.

PMID- 17450514
TI  - Photochemical and radiolytic production of an organic hydride donor with a Ru(II)
      complex containing an NAD+ model ligand.

PMID- 17450515
TI  - Singlet diradical character of an oxidized ruthenium trithiolate: electronic
      structure and reactivity.

PMID- 17450516
TI  - Dual reactivity pattern of allenolates "on water": the chemical basis for
      efficient allenolate-driven organocatalytic systems.
AB  - A study of the reactivity pattern associated with zwitterionic allenolates "on
      water" is reported. This study establishes the chemical basis for two
      organocatalyzed allenolate-driven reaction networks operating "on water". The
      first one is a chemodifferentiating three building block (ABB') three-component
      reaction (ABB' 3CR) manifold comprising terminal alkynoates and aldehydes. The
      manifold produces propargylic enol ethers 3 with higher average efficiency than
      their homologues in organic solvents. The second one is a novel organocatalytic
      system elicited by the reaction of alkynoates and nitrones in the presence of
      tertiary amines or phosphines. While terminal alkynoates afford 2,3,5
      trisubstituted 2,3-dihydroisoxazoles 5 and propargylic N-hydroxylamines 6,
      internal alkynoates selectively afford the 2,3,4,5-tetrasusbstituted 2,3
      dihydroisoxazaole 10. Importantly, in both cases, the 2,3-dihydroisoxazole ring
      is obtained as a sole regioisomer.

PMID- 17450517
TI  - A supramolecular multiposition rotary device.

PMID- 17450518
TI  - Prostacyclin inhibits endothelial cell XIAP ubiquitination and degradation.
AB  - To understand the role of prostacyclin (PGI(2)) in protecting endothelial cells
      from apoptosis, we evaluated the effects of carbaprostacyclin (cPGI(2)) on
      H(2)O(2)-induced human umbilical vein endothelial cell (HUVEC) apoptosis. cPGI(2)
      suppressed H(2)O(2)-induced annexin V-positive cells in a concentration- and time
      dependent manner. Pre-treatment of HUVEC with 50 microM cPGI(2) for 4 h produced
      the maximal anti-apoptotic effect. Authentic PGI(2) generated by adenoviral
      transfer of PGI(2) synthetic genes exerted a similar protective effect. cPGI(2)
      inhibited Smac/DIABLO release from mitochondria, caspase 3 activation, focal
      adhesion protein degradation, and cell detachment. cPGI(2) selectively protected
      X-linked inhibitor of apoptosis protein (X-linked IAP, XIAP) from H(2)O(2)
      induced ubiquitination, and preserved XIAP protein levels. PD-98059 but not H-89
      abrogated the protective action of cPGI(2). cPGI(2) increased ERK phosphorylation
      which was blocked by PD-98059. HUVEC stably transfected with dominant negative
      Ras abrogated XIAP preservation by cPGI(2) while constitutive active Ras
      increased ERK phosphorylation and protected XIAP from degradation. Our results
      demonstrate for the first time that PGI(2) inhibits XIAP ubiquitination and
      degradation via the Ras/MEK-1/ERK signaling pathway. Preservation of XIAP
      proteins represents a key mechanism by which PGI(2) protects endothelial cells
      from oxidant-induced apoptosis.

PMID- 17450519
TI  - No evidence for vasculogenesis regulation by angiostatin during mouse embryonic
      stem cell differentiation.
AB  - During embryogenesis, the formation of blood vessels proceeds by both
      vasculogenesis and angiogenesis. Both processes appear to be finely regulated. To
      date, factors and genes involved in the negative regulation of embryonic
      vasculogenesis remain largely unknown. Angiostatin is a proteolytic fragment of
      plasminogen that acts as an inhibitor of angiogenesis. In this study, we analyzed
      the potential role of angiostatin during early stages of embryonic stem (ES) cell
      endothelial in vitro differentiation, as a model of vasculogenesis. We found an
      early expression of the known angiostatin binding sites (angiomotin, alphav
      integrin and c-met oncogene) during ES cell differentiation. Nevertheless, we did
      not detect any significant effect of angiostatin on mesoderm induction and on
      differentiation commitment into cells of the endothelial lineage. In both control
      and angiostatin-treated conditions, the temporal and extent of formation of the
      Flk1 positive and Flk-1/CD31 (PECAM-1) positive cell populations were not
      significantly different. Quantitative RT-PCR experiments of endothelial gene
      expression (Flk-1, PECAM-1 and tie-2) confirm a lack of interference with early
      steps of endothelial differentiation in embryoid bodies. No evidence for an
      angiostatin effect on endothelial cord-like formation could be detected at later
      differentiation stages. On the other hand, angiostatin inhibits vascular
      endothelial growth factor-induced endothelial sprouting from embryoid bodies
      cultured in three dimensional type I collagen gels. Taken together, these
      findings support a selective inhibitory effect on the sprouting angiogenesis
      response for angiostatin during embryonic vascular development.

PMID- 17450520
TI  - Interference of 16.7-Hz electromagnetic fields on measured electrocardiogram.
AB  - The extent of electromagnetic interference (EMI) from 16.7-Hz alternate current
      power lines in the human surface electrocardiogram (ECG) was evaluated. Results
      showed a direct linear correlation between mean EMI and magnetic induction of 5.8
      21 microT on a railroad platform (electric field: 270 V/m). EMI inside a railroad
      car (10 microT, 0 V/m) was comparable to the electromagnetic field at the
      platform. Inside a voltage transformer substation (0 microT, 2000 V/m) EMI
      occurred only when the ECG device was closer to the power line than the test
      person. Magnetic induction caused 16.7-Hz EMI to a degree that proper diagnosis
      of ECG-rhythms was rendered impossible.

PMID- 17450521
TI  - Expression, localization and functions in acrosome reaction and sperm motility of
      Ca(V)3.1 and Ca(V)3.2 channels in sperm cells: an evaluation from Ca(V)3.1 and
      Ca(V)3.2 deficient mice.
AB  - In spermatozoa, voltage-dependent calcium channels (VDCC) have been involved in
      different cellular functions like acrosome reaction (AR) and sperm motility.
      Multiple types of VDCC are present and their relative contribution is still a
      matter of debate. Based mostly on pharmacological studies, low-voltage-activated
      calcium channels (LVA-CC), responsible of the inward current in spermatocytes,
      were described as essential for AR in sperm. The development of Ca(V)3.1 or
      Ca(V)3.2 null mice provided the opportunity to evaluate the involvement of such
      LVA-CC in AR and sperm motility, independently of pharmacological tools. The
      inward current was fully abolished in spermatogenic cells from Ca(V)3.2 deficient
      mice. This current is thus only due to Ca(V)3.2 channels. We showed that Ca(V)3.2
      channels were maintained in sperm by Western-blot and immunohistochemistry
      experiments. Calcium imaging experiments revealed that calcium influx in response
      to KCl was reduced in Ca(V)3.2 null sperm in comparison to control cells,
      demonstrating that Ca(V)3.2 channels were functional. On the other hand, no
      difference was noticed in calcium signaling induced by zona pellucida. Moreover,
      neither biochemical nor functional experiments, suggested the presence of
      Ca(V)3.1 channels in sperm. Despite the Ca(V)3.2 channels contribution in KCl
      induced calcium influx, the reproduction parameters remained intact in Ca(V)3.2
      deficient mice. These data demonstrate that in sperm, besides Ca(V)3.2 channels,
      other types of VDCC are activated during the voltage-dependent calcium influx of
      AR, these channels likely belonging to high-voltage activated Ca(2+) channels
      family. The conclusion is that voltage-dependent calcium influx during AR is due
      to the opening of redundant families of calcium channels.

PMID- 17450522
TI  - Synergistic antitumor effects of celecoxib with 5-fluorouracil depend on IFN
      gamma.
AB  - Cyclooxygenase-2 (COX-2) inhibitors are effective chemopreventive agents against
      colorectal cancers. For treatment of advanced cancers, combination of COX-2
      inhibitors and chemotherapy has been attempted, but the results are still
      controversial. In the present study, the effects of the COX-2 inhibitor celecoxib
      on the anticancer potential of chemotherapy, and its mechanisms of action were
      investigated in point of the angiogenesis, using an advanced cancer model in
      mice. BALB/c mice were inoculated with colon 26 cells. After the allograft grew
      up to 5 mm in diameter, the animals received celecoxib, 5FU, or a combination of
      5FU and celecoxib (5FU/celecoxib). After 21-days of the treatment, 5FU/celecoxib
      significantly inhibited the tumor growth and the tumor vessel density compared
      with the other groups. Celecoxib, 5FU or 5FU/celecoxib significantly suppressed
      the VEGF content in tumor tissues. 5FU/celecoxib also enhanced IFN-gamma levels
      in tumor tissue, which could be involved in the potent antitumor effects of
      5FU/celecoxib. This hypothesis was proven, because in IFN-gamma knockout (IFN
      gamma(-/-)) mice, the inhibitory effects of 5FU/celecoxib on angiogenesis and
      tumor growth were significantly impaired compared with that in wild type mice.
      These results suggest that celecoxib enhances the antitumor effect of 5FU against
      an advanced colon cancer model by suppressing angiogenesis. In addition to VEGF,
      IFN-gamma has pivotal roles in tumor suppression induced by celecoxib.

PMID- 17450523
TI  - Gene expression profiling in melanoma identifies novel downstream effectors of
      p14ARF.
AB  - p14ARF is inactivated by deletions/mutations in many cancer types and can
      suppress cell growth by both p53-dependent and p53-independent mechanisms. To
      identify novel downstream effectors of p14ARF, we used gene expression profiling
      as a primary screening tool to select candidates for follow up validation studies
      using in vitro cell-based assays. Gene expression profiles of a panel of 35
      melanoma cell lines with either wild-type (n = 12) or mutant (n = 23) p14ARF were
      compared to identify genes associated with inactivation of p14ARF. Analysis of
      the microarray data identified 1,316 probe sets that were significantly (p <
      0.01) differentially expressed between the p14ARF wild-type and mutant cell
      lines. Pathway analysis of these genes showed an overrepresentation of many
      receptor-mediated signal transduction pathways, e.g. TGFbeta, EGF, HGF, PDGF,
      MAPK, Wnt and integrin pathways. A number of components of these pathways,
      including FLRT3, RUNX2, MIG-6 and SMURF2 were confirmed as downstream targets of
      p14ARF using p14ARF-inducible cell lines and RNAi. We propose that regulation of
      these genes may contribute to melanoma development when p14ARF function is lost.

PMID- 17450524
TI  - Long-term population-based marriage rates among adult survivors of childhood
      cancer in Britain.
AB  - The objectives of this study were to assess the number of adult survivors of
      childhood cancer who ever married and the factors influencing marriage, compare
      observed marriages to those expected from the general population, and assess age
      at marriage and influencing factors. The data is based on the British Childhood
      Cancer Survivor Study (BCCSS), which is a population-based cohort of 18,119
      individuals who were diagnosed with childhood cancer between 1940 and 91 and
      survived at least 5 years. Fourteen thousand five hundred thirty-nine were alive,
      aged at least 16 years and eligible to receive a postal questionnaire, which
      ascertained marriage status. Thirty-four percent of 9,954 survivors had married.
      Survivors with the following characteristics: males, CNS neoplasm, received
      radiotherapy, diagnosed with mental retardation, registered blind, low social
      functioning score (calculated from SF-36 health status measure), and achieved the
      highest level of educational attainment, were less likely to have married than
      the complementary survivor groups. The deficits in the proportion ever married
      compared to the general population were mostly between 9 and 18% among males and
      7-10% among females. The largest ever married deficits were among male CNS
      neoplasm survivors aged 30 years or over (29-38%). Age at first marriage among
      survivors was related to: sex, childhood cancer type, age at diagnosis,
      chemotherapy, radiotherapy, mental retardation, and level of educational
      attainment. Regular follow-up for these survivors should address not just
      physical late-effects of the childhood cancer and treatment, but also
      psychosocial needs throughout the lifespan of the survivors to help them achieve
      life events as they occur in the general population.

PMID- 17450525
TI  - Family history of gallstones and the risk of biliary tract cancer and gallstones:
      a population-based study in Shanghai, China.
AB  - Cancers of the biliary tract arise from the gallbladder, extrahepatic bile ducts
      and ampulla of Vater. Although relatively uncommon, the incidence of biliary
      tract cancer rose more than 100% in Shanghai, China between 1972 and 1994.
      Gallstones are the predominant risk factor for biliary tract cancers, with over
      60% of the cancer cases having gallstones. A familial tendency to gallstones has
      been reported and may elevate the risk of gallbladder cancer further. As part of
      a large population-based case-control study of biliary tract cancers in Shanghai,
      China, we examined the association between a family history of gallstones and
      biliary tract cancers as well as biliary stones. A total of 627 biliary tract
      cancers (368 gallbladder, 191 bile duct, 68 ampulla of Vater), 1,037 biliary
      stone cases (774 gallbladder, 263 bile duct) and 959 healthy subjects randomly
      selected from the population were included in this study. Information on family
      history of gallstones among first-degree relatives (i.e., parents, siblings,
      offspring) was obtained through a self-reported history during in-person
      interviews. A family history of gallstones was associated with increased risks of
      biliary stones [odds ratio (OR) = 2.8, 95% confidence interval (CI) = 2.1-3.8],
      gallbladder cancer (OR = 2.1, 95% CI = 1.4-3.3) and bile duct cancer (OR = 1.5,
      95% CI = 0.9-2.5), after adjustment for age, gender, marital status, education,
      smoking, alcohol drinking and body mass index. For gallbladder cancer, subjects
      with gallstones but without a family history of gallstones had a 21-fold risk
      (95% CI 14.8-30.1), while those with both gallstones and a positive family
      history had a 57-fold risk (95% CI 32.0-110.5). Significant risks for gallbladder
      cancer persisted after additional adjustment for gallstones, and when the
      analysis was restricted to subjects with first-degree relatives whose gallstones
      were treated with cholecystectomy. The significant associations with a family
      history of gallstones were seen for all first-degree relatives, including
      parents, siblings and offspring, but not spouses. This large population-based
      study not only supports the role of gallstones in biliary carcinogenesis but also
      suggests that the underlying genetic or lifestyle determinants of stones within
      families contribute to the risk of biliary tract cancer.

PMID- 17450526
TI  - Protein C inhibitor inhibits breast cancer cell growth, metastasis and
      angiogenesis independently of its protease inhibitory activity.
AB  - Protein C inhibitor (PCI) regulates the anticoagulant protein C pathway and also
      inhibits urinary plasminogen activator (uPA), a mediator of tumor cell invasion.
      In the present study, we evaluated the effect of human PCI and its inactive
      derivatives on tumor growth and metastasis of human breast cancer (MDA-231)
      cells, and on angiogenesis in vivo. The invasiveness of MDA-231 cells was
      inhibited by recombinant intact PCI, but not by reactive site-modified PCI
      (R354APCI) or by the N-terminal fragment of protease-cleaved PCI (NTPCI). The in
      vitro invasiveness of MDA-231 cells expressing intact PCI (MDA-PCI) was
      significantly decreased as compared to MDA-231 cells expressing R354APCI (MDA
      R354APCI) or NTPCI (MDA-NTPCI). Further, in vivo growth and metastatic potential
      of MDA-PCI, MDA-R354APCI and MDA-NTPCI cells in severe combined immunodeficient
      (SCID) mice were significantly decreased as compared to MDA-Mock cells.
      Angiogenesis was also significantly decreased in Matrigel implant containing MDA
      PCI, MDA-R354APCI or MDA-NTPCI cells as compared to that containing MDA-Mock
      cells. In vivo angiogenesis in rat cornea and in vitro tube formation were also
      inhibited by recombinant intact PCI, R354APCI and NTPCI. Furthermore, the anti
      angiogenic activity of PCI was strong as cleaved antithrombin (AT), and slightly
      stronger than that of plasminogen activator inhibitor (PAI)-1 and pigment
      epithelium-derived factor (PEDF). Overall, this study showed that, in addition to
      a reactive site-dependent mechanism, PCI may also regulate tumor growth and
      metastasis independently of its protease inhibitory activity by inhibiting
      angiogenesis.

PMID- 17450527
TI  - Coffee consumption and risk of colorectal cancer in a population-based
      prospective cohort of Japanese men and women.
AB  - We prospectively examined the association between coffee consumption and the risk
      of developing colorectal cancer in a large population-based cohort study (the
      JPHC Study) of Japanese men and women. Data were analyzed from a population-based
      cohort of 96,162 subjects (46,023 men and 50,139 women). A total of 1,163
      incident colorectal cancers were identified during the follow-up period,
      including 763 cases of colon cancer and 400 of rectal cancer. We observed a
      significant inverse association between coffee consumption and the risk of
      developing invasive colon cancer among women. Compared with those who almost
      never consumed coffee, women who regularly consumed 3 or more cups of coffee per
      day had a RR of 0.44 (95% CI = 0.19-1.04; p for trend = 0.04) after adjustment
      for potential confounding factors. However, no significant association was found
      for rectal cancer in women. In men, no significant decrease was observed in any
      colorectal cancer site. Further, additional analyses on the association of green
      tea consumption with colorectal cancer risk found no significant association in
      men or women. These findings suggest that coffee consumption may lower the risk
      of colon cancer among Japanese women.

PMID- 17450528
TI  - A gene expression signature associated with metastatic cells in effusions of
      breast carcinoma patients.
AB  - Malignant effusion in invasive breast carcinoma is associated with poor
      prognosis. To decipher molecular events leading to metastasis and to identify
      reliable markers for targeted therapies are of crucial need. Therefore, we have
      used cDNA microarrays to delineate molecular signatures associated with
      metastasis and relapse in breast carcinoma effusions. Taking advantage of an
      immunomagnetic method, we have purified to homogeneity EpCAM-positive cells from
      34 malignant effusions. Immunopurified cells represented as much as 10% of the
      whole cell fraction and their epithelial and carcinoma features were confirmed by
      immunofluorescence labeling. Gene expression profiles of 19 immunopurified
      effusion samples, were analyzed using human pan-genomic microarrays, and compared
      with those of 4 corresponding primary tumors, 8 breast carcinoma effusion-derived
      cell lines, and 4 healthy mammary tissues. Principal component and multiple
      clustering analyses of microarray data, clearly identified distinctive molecular
      portraits corresponding to the 4 categories of specimens. Of uppermost interest,
      effusion samples were arranged in 2 subsets on the basis of their gene expression
      patterns. The first subset partly shares a gene expression signature with the
      different cell lines, and overexpresses CD24, CD44 and epithelial cytokeratins
      8,18,19. The second subset overexpresses markers related to aggressive invasive
      carcinoma (uPA receptor, S100A4, vimentin, CXCR4). These findings demonstrate the
      importance of using pure cell fractions to accurately decipher in silico gene
      expression of clinical specimens. Further studies will lead to the identification
      of genes of oustanding importance to diagnose malignant effusion, predict
      survival and tailor appropriate therapies to the metastatic effusion disease in
      breast carcinoma patients.

PMID- 17450529
TI  - Cyclooxygenase-1, but not -2, in blast cells of patients with acute leukemia.

PMID- 17450530
TI  - Risk factors for prostate cancer incidence and progression in the health
      professionals follow-up study.
AB  - Risk factors for prostate cancer could differ for various sub-groups, such as for
      "aggressive" and "non-aggressive" cancers or by grade or stage. Determinants of
      mortality could differ from those for incidence. Using data from the Health
      Professionals Follow-Up Study, we re-examined 10 factors (cigarette smoking
      history, physical activity, BMI, family history of prostate cancer, race, height,
      total energy consumption, and intakes of calcium, tomato sauce and alpha
      linolenic acid) using multivariable Cox regression in relation to multiple
      subcategories for prostate cancer risk. These were factors that we previously
      found to be predictors of prostate cancer incidence or advanced prostate cancer
      in this cohort, and that have some support in the literature. In this analysis,
      only 4 factors had a clear statistically significant association with overall
      incident prostate cancer: African-American race, positive family history, higher
      tomato sauce intake (inversely) and alpha-linolenic acid intake. In contrast, for
      fatal prostate cancer, recent smoking history, taller height, higher BMI, family
      history, and high intakes of total energy, calcium and alpha-linolenic acid were
      associated with a statistically significant increased risk. Higher vigorous
      physical activity level was associated with lower risk. In relation to these risk
      factors, advanced stage at diagnosis was a good surrogate for fatal prostate
      cancer, but high-grade (Gleason >/= 7 or Gleason >/= 8) was not. Only for high
      calcium intake was there a close correspondence for associations among high-grade
      cancer, advanced and fatal prostate cancer. Tomato sauce (inversely) and alpha
      linolenic acid (positively) intakes were strong predictors of advanced cancer
      among those with low-grade cancers at diagnosis. Although the proportion of
      advanced stage cancers was much lower after PSA screening began, risk factors for
      advanced stage prostate cancers were similar in the pre-PSA and PSA era. The
      complexity of the clinical and pathologic manifestations of prostate cancer must
      be considered in the design and interpretation of studies.

PMID- 17450532
TI  - Correlation between tumor blood flow assessed by perfusion CT and effect of
      neoadjuvant therapy in advanced esophageal cancers.
AB  - BACKGROUND: Redundant blood supply by angiogenesis is a great advantage for the
      continuous growth of solid tumors. However, with chemotherapy (ChT), it can be
      disadvantageous due to increased drug delivery. An objective, reproducible, and
      non-invasive method for evaluating tumor blood supply is offered by perfusion CT.
      METHODS: Fifty-five advanced esophageal cancers (95% squamous cell carcinomas)
      were evaluated for hemodynamic parameters, including blood flow (BF), blood
      volume (BV), and mean transit time (MTT) of primary tumor by perfusion CT scan.
      Forty-six underwent neoadjuvant therapy (36 ChT and 10 chemoradiotherapy (CRT))
      as primary treatment of the cancer and 36 underwent esophagectomy. RESULTS:
      Clinicopathological parameters were not significantly associated with hemodynamic
      parameters, except for hematogenic metastasis, which was not frequent (seven
      patients), but significantly associated with high BF (P = 0.0165). High BF and
      low MTT correlated significantly with a good response by neoadjuvant therapies (P
      = 0.0004 and P = 0.0124), while BV did not. The patients with high BF more
      frequently underwent esophagectomy and displayed better prognosis than those with
      lower values, while neither BV nor MTT was associated with patient survival.
      CONCLUSIONS: Tumor BF by perfusion CT can partly predict the effect of ChT and
      CRT and survival. Further large cohort studies in homogeneous patient groups will
      reveal its clinical usefulness.

PMID- 17450531
TI  - Separase, securin and Rad21 in neural cell growth.
AB  - The key mitotic regulator securin is expressed at low levels in fetal brain
      compared with adult, and modulates the proliferation of human embryonic neuronal
      N-Tera2 (NT2) cells. We now examine the function and expression of securin's
      interacting partner separase, along with Rad21, the functional component of
      cohesin, which is cleaved by separase following interaction with securin. In
      contrast to securin, the cleaved forms of separase and Rad21 were highly
      expressed in human fetal cerebral cortex compared with adult. In a murine model
      of absent securin expression - the PTTG knock-out mouse - separase and Rad21 were
      over-expressed in multiple brain regions. In addition, cDNA array analysis of
      other key mitotic regulators additionally identified cyclin C and sestrin 2 to be
      induced in the brains of securin-null mice compared with wild type. Further,
      Rad21 mRNA expression was highly correlated with that of securin, separase,
      cyclin C and sestrin 2 in fetal brains. In embryonic neuronal NT2 cells, siRNA
      repression of separase failed to significantly alter cell turnover, whereas
      repression of securin expression resulted in increased levels of the activated
      forms of Rad21 and separase, and promoted cell proliferation. Our data suggest
      that the co-ordinated expression of separase, securin and Rad21 is fundamental
      for the developing brain.

PMID- 17450533
TI  - CEC and EKC of natural compounds.
AB  - In this review, an overview of CEC and EKC methods with their developments are
      summarized for different natural compounds. It is divided into three main parts.
      The first part elaborates the separation of lipophilic compounds without any
      charged groups. The second part constitutes CEC and EKC of lipophilic compounds
      containing ionizable functional groups whereas the third part contains
      hydrophilic compounds. Packed, monolithic, coated, or raw fused-silica (FS)
      capillaries are among the choice for stationary phases. Applications of these
      phases on the above-mentioned three classes of compounds, coupled with different
      detection methods, e.g. MS or LIF, are explored and their advantages and
      disadvantages are discussed.

PMID- 17450534
TI  - A comparative study of micellar and microemulsion EKC for the analysis of
      benzoylurea insecticides and their analogs.
AB  - An investigation of the basic factors which govern the microemulsion EKC (MEEKC)
      and MEKC for the separation of four benzoylurea (BU) insecticides and their four
      analogs was carried out. In MEEKC, the separation of eight BU compounds was
      optimized by changing the microemulsion composition, such as concentration of
      SDS, octane, n-butanol, and isopropanol percentages, as well as capillary
      temperature. Separation optimization was also carried out for MEKC, showing that
      ACN and a high level of another additive gamma-CD were needed to achieve
      effective separation of these analytes. Although separation with baseline
      resolution was achieved by either MEEKC or MEKC methods, the separation
      selectivity resulting from the proposed MEEKC method was completely different
      from that of MEKC. In addition, analytical time in MEEKC was longer than that in
      MEKC, but in view of theoretical plate numbers, detection limits, and
      reproducibility, both methods were effective for the analysis of BU insecticides
      and their analogs.

PMID- 17450535
TI  - Electrophoretic affinity measurements on microchip. Determination of binding
      affinities between diketopiperazine receptors and peptide ligands.
AB  - ACE on a microchip (MC-ACE) is introduced as a fast and reliable method to
      determine binding affinities. It is based on monitoring the change in the ionic
      mobility of a receptor upon binding to a ligand, or vice versa. The method is
      complementary to other standard methods for binding affinity determinations, like
      isothermal titration calorimetry (ITC), NMR, UV-Vis spectroscopy, etc. and allows
      for affinity studies of weak to strong binding interactions. The method is
      attractive since it principally allows for the analysis of the binding affinity
      of multiple receptors to a given ligand and requires comparatively small
      quantities of the binding partners (particularly in comparison to affinity
      measurements on capillary). We demonstrate the applicability of MC-ACE for the
      determination of the binding affinities between acid-rich diketopiperazine
      receptors and basic tripeptides in aqueous solution.

PMID- 17450536
TI  - Electrochromatography in poly(dimethyl)siloxane microchips using organic
      monolithic stationary phases.
AB  - This paper shows the in situ synthesis of an hexyl acrylate monolith in PDMS
      microfluidic devices and its subsequent use as stationary phase for
      electrochromatography on chip. To overcome the ability of PDMS material to absorb
      organic monomers, surface modification of the enclosed channels was realized by
      UV-mediated graft polymerization. This grafting procedure is based on the
      preliminary adsorption of a photoinitiator onto the PDMS surface and
      polymerization of charged monomers. Next, hexyl acrylate monoliths were cast in
      situ using photopolymerization process. The chromatographic behavior of the
      monolithic column was confirmed by the successful separation of derivatized
      catecholamines in the PDMS device using a 30 mm effective separation length (100
      microm x 100 microm section). Efficiencies reached up to 200,000 plates per
      meter.

PMID- 17450537
TI  - Determination of sertraline and N-desmethylsertraline in human plasma by CE with
      LIF detection.
AB  - A method has been developed for the analysis of the antidepressant drug
      sertraline together with its main metabolite N-desmethylsertraline (DMS) in human
      plasma. It is based on CE with LIF detection (lambda = 488 nm). A SPE procedure
      is employed for biological sample pretreatment, followed by a derivatization step
      with FITC; reboxetine was the internal standard. The effect of CD, acetone and N
      methyl-D-glucamine (GLC) as constituents of the BGE for analyte separation was
      investigated. The final BGE consisted of 20 mM carbonate buffer, pH 9.0, with 2.5
      mM heptakis(2,6-di-O-methyl)-beta-CD, 50 mM GLC and 20% v/v acetone. With 30 kV
      applied voltage, the electrophoretic run is completed in 7.5 min. Linearity was
      observed in the plasma concentration range from 3.0 to 500 ng/mL for sertraline
      and 4.0 to 500 ng/mL for DMS. Extraction yield was >97.1%, precision - expressed
      as RSD% - was <3.7, accuracy (recovery) was >95.6%. Due to its sensitivity and
      selectivity, the method was suited for the analysis of plasma samples from
      patients undergoing therapy with sertraline.

PMID- 17450538
TI  - Separation of cold medicine ingredients using a precise MEKC method at elevated
      pH.
AB  - An MEKC method was developed in order to separate a cold medicine formulation
      containing acetaminophen, ephedrine sulfate, doxylamine succinate, and
      dextromethorphan hydrobromide as active pharmaceutical ingredients. Because of
      their similar physical and chemical properties, it was a challenge to separate
      the basic compounds without sample pretreatment. In addition, the high content of
      alcohol and sucrose together with the variety of further excipients had to be
      considered. Thus, the complex matrix required several optimization steps. These
      included the search for the optimum pH and for a suitable sodium dodecyl sulfate
      concentration to avoid matrix-capillary wall interaction and to ensure precision.
      As a second developing step, an internal standard (benzocaine) was chosen to
      guarantee a high level of quantitative performance. An RSD% value of the peak
      areas between 1.0 and 2.0 was reached. The employed method development strategy
      can be generalized to similar separation approaches in the future.

PMID- 17450539
TI  - Fabrication and characterization of open-tubular CEC modified with tentacle-type
      metal-chelating polymer chains.
AB  - A novel stationary phase with tentacle-type metal-chelating polymer chains was
      fabricated for open-tubular CEC. The preparation procedure of the stationary
      phase included the synthesis of monomer, silanization of capillary inner wall, in
      situ polymerization, and metal complexation. The effects of initiator
      concentration and reaction time on the column capacity were investigated. To
      compare with the tentacle-type metal-chelating capillary column, a monolayer
      ligand-modified capillary was also prepared. Immobilized copper(II) capacity of
      the tentacle-type polymer stationary phase was nearly 900 times higher than that
      of the monolayer one. The electroosmotic mobility was examined for its dependence
      on pH as well as phosphate and ACN concentrations. The tentacle-type metal
      chelating capillary with high ligand capacity has proven to afford better
      retention and resolution for the separation of phenylalanine, tryptophan, and
      tyrosine mixtures and three purine derivatives. The separation was considered to
      be effected by a combination of ligand exchange and electrophoretic mobility.

PMID- 17450540
TI  - Recurrent laryngeal cancer presenting as delayed hypoparathyroidism.
AB  - BACKGROUND: Endocrine dysfunction following therapy for head and neck cancer has
      been previously described. Permanent hypoparathyroidism may result from the
      tumor, surgery, or radiation therapy. However, the incidence and significance of
      delayed hypoparathyroidism following treatment for laryngeal cancer remains
      unclear. METHODS AND RESULTS: We report a patient who had stable serum calcium
      measurements on serial testing following concurrent chemoradiation and salvage
      laryngectomy for locally advanced laryngeal cancer. The patient subsequently
      presented 32 months following salvage laryngectomy with new onset, symptomatic
      hypocalcemia secondary to hypoparathyroidism. Subsequent evaluation revealed
      local recurrence. CONCLUSION: To our knowledge, this case represents the first
      report of delayed hypoparathyroidism as the presenting manifestation of
      recurrence following treatment for laryngeal cancer. Possible pathophysiologic
      mechanisms are discussed.

PMID- 17450541
TI  - Evaluation of candidate genes for DYX1 and DYX2 in families with dyslexia.
AB  - Dyslexia is a common heterogeneous disorder with a significant genetic component.
      Multiple studies have replicated the evidence for linkage between variously
      defined phenotypes of dyslexia and chromosomal regions on 15q21 (DYX1) and 6p22.2
      (DYX2). Based on association studies and the possibility for functional
      significance of several polymorphisms, candidate genes responsible for the
      observed linkage signal have been proposed-DYX1C1 for 15q21, and KIAA0319 and
      DCDC2 for 6p22.2. We investigated the evidence for contribution of these
      candidate genes to dyslexia in our sample of multigenerational families. Our
      previous quantitative linkage analyses in this dataset provided supportive
      evidence for linkage of dyslexia to the locus on chromosome 15, but not to the
      locus on chromosome 6. In the current study, we used probands from 191 families
      for a case control analysis, and proband-parent trios for family-based TDT
      analyses. The observation of weak evidence for transmission disequilibrium for
      one of the two studied polymorphisms in DYX1C1 suggests involvement of this gene
      in dyslexia in our dataset. We did not find evidence for the association of
      KIAA0319 or DCDC2 alleles to dyslexia in our sample. We observed a slight
      tendency for an intronic deletion in DCDC2 to be associated with worse
      performance on some quantitative measures of dyslexia in the probands in our
      sample, but not in their parents.

PMID- 17450542
TI  - Daily computer usage correlated with undergraduate students' musculoskeletal
      symptoms.
AB  - BACKGROUND: A pilot prospective study was performed to examine the relationships
      between daily computer usage time and musculoskeletal symptoms on undergraduate
      students. METHODS: For three separate 1-week study periods distributed over a
      semester, 27 students reported body part-specific musculoskeletal symptoms three
      to five times daily. Daily computer usage time for the 24-hr period preceding
      each symptom report was calculated from computer input device activities measured
      directly by software loaded on each participant's primary computer. General
      Estimating Equation models tested the relationships between daily computer usage
      and symptom reporting. RESULTS: Daily computer usage longer than 3 hr was
      significantly associated with an odds ratio 1.50 (1.01-2.25) of reporting
      symptoms. Odds of reporting symptoms also increased with quartiles of daily
      exposure. CONCLUSIONS: These data suggest a potential dose-response relationship
      between daily computer usage time and musculoskeletal symptoms.

PMID- 17450543
TI  - Job categories and acute ischemic heart disease: a hospital-based, case-control
      study in Taiwan.
AB  - BACKGROUND: Most studies of the relationship between work and acute ischemic
      heart disease (IHD) were performed in western populations, and the extent to
      which their findings hold in Asian populations is largely unknown. The purpose of
      this study was to examine the association between job categories and non-fatal,
      first episodes of acute IHD in Taipei, Taiwan. METHODS: A hospital-based, case
      control design was used. Cases were patients with a first episode of non-fatal
      acute IHD who were admitted to the department of cardiology. Two controls without
      known cardiovascular disease were matched to each case for age, gender, and date
      of admission. A total of 119 cases and 238 controls were enrolled between April
      and September 2004. RESULTS: Compared with white-collar workers, blue-collar
      workers had a 5.3-fold (95% CI: 1.5, 18.5) increased risk of a first episode of
      non-fatal acute IHD, while self-employed workers and managers/professionals had a
      slightly lower odds ratio of 0.6 (95% CI: 0.1, 2.4) and 0.5 (95% CI: 0.1, 2.2),
      respectively. Hypertension, diabetes, obesity, physical inactivity, and sleep
      disturbance were significant risk factors for acute IHD. A clustering of the
      cardiovascular risk factors was found in blue-collar workers. CONCLUSIONS: Blue
      collar workers had a 5.3-fold increased risk of a first event of non-fatal acute
      IHD compared with white-collar workers, and this increased risk was associated
      with a clustering of cardiovascular risk factors.

PMID- 17450544
TI  - Ischemic heart disease mortality among miners and other potentially silica
      exposed workers.
AB  - BACKGROUND: Some previous studies have observed an increased mortality regarding
      ischemic heart disease (IHD) among miners and industrial sand workers. The
      purpose was to study the occurrence of IHD mortality among silica-exposed
      workers. METHODS: Male miners, well borers, dressing plant workers, and other
      mine and stone workers were identified in the Swedish National Census of 1970.
      The total cohort (n = 11,896) was followed from 1970 until December 31, 1995 and
      linked to the Cause of Death Register. The referent group comprised all gainfully
      employed men identified in the same census. The Standardized Mortality Ratio was
      calculated as the ratio between observed and expected numbers of deaths. RESULT:
      An increased risk due to IHD mortality was observed among miners, well borers,
      dressing plant workers, and other mine and stone workers. CONCLUSION: These
      results indicate a possible relation between silica-dust exposure and IHD. The
      increased risk of IHD mortality is unlikely explained by smoking habits. Shift
      work might explain some of the increased risk. A low-grade inflammation in the
      lungs as a result of dust exposure is discussed as a possible cause. However, the
      key message is that better dose estimates and better confounding control is
      needed to study the possible relation between silica-dust exposure and IHD.

PMID- 17450545
TI  - Genetic connections of the actin cytoskeleton and beyond.
AB  - Actin is a key protein in numerous cellular functions. One recent study has
      identified a large set of genes, associated with the actin cytoskeleton, which
      could be grouped into a wide spectrum of cytoplasmic and nuclear functions, such
      as protein biosynthesis and gene transcription. Deletions of many of the
      identified genes affected cellular actin organization, suggesting a functional
      link between different actin fractions probably regulated through changes in
      actin dynamics. The data are very exciting; speculations on the crosstalk between
      cytoplasmic and nuclear actin fractions in different cellular contexts may help
      placing the results in perspective to further understand how actin-mediated
      signalling affects cellular functions, such as gene expression.

PMID- 17450546
TI  - Bladder cancer and occupation: a report from the Belgian case-control study on
      bladder cancer risk.
AB  - BACKGROUND: The aim of this study was to add to the data on associations between
      occupation and bladder cancer thereby strengthening the case for focused research
      on specific occupational categories. METHODS: Two hundred two cases and 390
      controls participated in this population-based case-control study. Age, sex,
      smoking, and education adjusted odds ratios (ORs) were calculated for each
      occupation by unconditional logistic regression. RESULTS: The occupational group
      of domestic helpers, cleaners, and launderers exhibited a significantly elevated
      risk of bladder cancer. Elevated non-significant risks (OR > 1.5) were observed
      for painters and varnishers, electronic equipment assemblers, general laborers,
      building finishers, carpenters and joiners, architects and engineers, and textile
      and garment workers. CONCLUSIONS: This study suggests that domestic helpers,
      cleaners, and launderers probably experience an increased risk of bladder cancer.
      Although no other occupations showed significantly increased risks, the non
      significantly elevated risks for painters, carpenters, and textile workers could
      be confirmed by results from earlier studies.

PMID- 17450547
TI  - Structural, electronic, and optical properties of 9-heterofluorenes: a quantum
      chemical study.
AB  - Density-functional theory studies were applied to investigate the structural,
      electronic, and optical properties of 9-heterofluorenes achieved by substituting
      the carbon at 9 position of fluorene with silicon, germanium, nitrogen, phosphor,
      oxygen, sulfur, selenium, or boron. These heterofluorenes and their oligomers up
      to pentamers are highly aromatic and electrooptically active. The alkyl and aryl
      substituents of the heteroatom have limited influence, but the oxidation of the
      atom has significant influence on their molecular structures and properties. The
      highest occupied molecular orbital (HOMO)-lowest occupied molecular orbital
      (LUMO) interaction theory was successfully applied to analyze the energy levels
      and the frontier wave functions of these heterofluorenes. Most heterofluorenes
      belong to type B of interaction with low-lying LUMO and have the second kind of
      wave function. Carbazole and selenafluorene have type C of interaction with high
      lying HOMO and the third kind of wave function. Types C and D of heterofluorenes,
      such as carbazole, oxygafluorene, sulfurafluorene, and selenafluorene also have
      high triplet state energies. The extrapolated HOMO and LUMO for
      polyheterofluorenes indicate that polyselenonafluorene has the lowest LUMO;
      polycarbazole has the highest HOMO; polyselenafluorene has the highest bandgap
      (E(g)); and polyborafluorene has the lowest E(g). Heterofluorenes and their
      oligomers and polymers are of great experimental interests, especially those
      having extraordinary properties revealed in this study.

PMID- 17450548
TI  - Protein structure prediction aided by geometrical and probabilistic constraints.
AB  - Database-assisted ab initio protein structure prediction methods have exhibited
      considerable promise in the recent past, with several implementations being
      successful in community-wide experiments (CASP). We have employed combinatorial
      optimization techniques toward solving the protein structure prediction problem.
      A Monte Carlo minimization algorithm has been employed on a constrained search
      space to identify minimum energy configurations. The search space is constrained
      by using radius of gyration cutoffs, the loop backbone dihedral probability
      distributions, and various secondary structure packing conformations. Simulations
      have been carried out on several sequences and 1000 conformations have been
      initially generated. Of these, 50 best candidates have then been selected as
      probable conformations. The search for the optimum has been simplified by
      incorporating various geometrical constraints on secondary structural elements
      using distance restraint potential functions. The advantages of the reported
      methodology are its simplicity, and modifiability to include other geometric and
      probabilistic restraints.

PMID- 17450549
TI  - Algorithm to evaluate rate constants for polyatomic chemical reactions. I. Theory
      and computational details.
AB  - A classical reaction path, Liouville algorithm, as previously developed by the
      authors, has been reformulated in a more efficient form, based on the time
      dependent first integral method from the theory of partial differential
      equations. Both the theory and computational details are presented. The
      formulation is based on solving the complete rate constant problem, concerning
      both the density distribution as well as the reactive flux, by means of solving
      the classical Liouville equation. The numerical implementation is discussed in
      detail, including some specifics concerning the reaction path calculation. The
      formulation is tested with the well-known Muller-Brown bidimensional potential
      energy surface.

PMID- 17450550
TI  - Common system setup for the entire catalytic cycle of cytochrome P450(cam) in
      quantum mechanical/molecular mechanical studies.
AB  - We describe a system setup that is applicable to all species in the catalytic
      cycle of cytochrome P450(cam). The chosen procedure starts from the X-ray
      coordinates of the ferrous dioxygen complex and follows a protocol that includes
      the careful assignment of protonation states, comparison between different
      conceivable hydration schemes, and system preparation through a series of
      classical minimizations and molecular dynamics (MD) simulations. The resulting
      setup was validated by quantum mechanical/molecular mechanical (QM/MM)
      calculations on the resting state, the pentacoordinated ferric and ferrous
      complexes, Compound I, the transition state and hydroxo intermediate of the C--H
      hydroxylation reaction, and the product complex. The present QM/MM results are
      generally consistent with those obtained previously with individual setups.
      Concerning hydration, we find that saturating the protein interior with water is
      detrimental and leads to higher structural flexibility and catalytically
      inefficient active-site geometries. The MD simulations favor a low water density
      around Asp251 that facilitates side chain rotation of protonated Asp251 during
      the conversion of Compound 0 to Compound I. The QM/MM results for the two
      preferred hydration schemes (labeled SE-1 and SE-4) are similar, indicating that
      slight differences in the solvation close to the active site are not critical as
      long as camphor and the crystallographic water molecules preserve their positions
      in the experimental X-ray structures.

PMID- 17450551
TI  - Geometry optimization using generalized, chemically meaningful constraints.
AB  - An external geometry optimizer (BOptimize) is described that can be used together
      with a number of existing quantum-chemical codes (Gaussian, Gamess-UK, Turbomole,
      ADF, Orca, Priroda, Spartan-PM3, Mopac) and allows flexible and general
      constrained optimizations. Some details of the implementation are discussed, and
      examples are provided of constrained optimizations that would be difficult or
      impossible to perform with existing optimizers.

PMID- 17450552
TI  - Genetic algorithm for the determination of binodal curves in ternary systems
      polymer-liquid(1)-liquid(2) and polymer(1)-polymer(2)-solvent.
AB  - A simple genetic algorithm for the numerical evaluation of binodal curves in
      ternary systems polymer-liquid (1)-liquid (2) and polymer (1)-polymer (2)-solvent
      is presented. The technique exploits a specifically developed restarting
      technique based on a combined elitist and zooming strategy on the last population
      at each iteration. The objective function (fitness) is represented by the
      weighted sum of the squared differences of chemical potentials of the two phases
      of each component, obtained evaluating first derivatives of Gibbs free energy of
      the mixture with respect to the number of moles of the components. The method
      proposed (a) is numerically stable since it does not require the evaluation of
      first derivatives of the objective function and (b) can be applied in a wide
      range of cases changing the equation of state. Several comparisons with
      simplified iterative procedures presented in the past in the technical literature
      both for mixtures of two polymers with identical characteristics in a solvent and
      for mixtures of solvent-nonsolvent-polymer with solvent-polymer interaction
      parameter equal to zero are reported. Finally, a comparison between present
      results and the "alternating tangent approach" is reported for two technically
      meaningful binary systems, when a simplified PC-SAFT equation of state is
      adopted. The comparisons show that reliable results can be obtained by means of
      the algorithm proposed and suggest that the procedure presented can be used for
      practical purposes.

PMID- 17450553
TI  - Peptide reagent design based on physical and chemical properties of amino acid
      residues.
AB  - It has tremendous values for both drug discovery and basic research to develop a
      solid bioinformatical tool for guiding peptide reagent design. Based on the
      physical and chemical properties of amino acids, a new strategy for peptide
      reagent design, the so-called AABPD (amino acid based-peptide design), is
      proposed. The peptide samples in a training dataset are described by a series of
      HMLP (heuristic molecular lipophilicity potential) parameters and other
      physicochemical properties of amino acid residues that form a three-dimensional
      data matrix where each component is defined by three indexes: the first index
      refers to the peptide samples, the second to the amino acid positions, and the
      third to the amino acid parameters. The binding free energy between a peptide
      ligand and its protein receptor is calculated by a linear free energy equation
      through the physicochemical parameters, resulting in a set of simultaneous linear
      equations between the bioactivity of the peptides and the physicochemical
      properties of amino acids. An iterative double least square technique is
      developed for the solution of the three-dimensional simultaneous linear equation
      set to determine the amino acid position coefficients of peptide sequence and the
      physicochemical parameter coefficients of amino acid residues alternately. The
      two sets of coefficients thus obtained are used for predicting the bioactivity of
      other query peptide reagents. Two calculation examples, the peptide substrate
      specificity of the SARS coronavirus 3C-like proteinase and the affinity
      prediction for epitope-peptides with Class I MHC molecules are studied by using
      the peptide reagent design strategy.

PMID- 17450554
TI  - New six-site acetonitrile model for simulations of liquid acetonitrile and its
      aqueous mixtures.
AB  - A new six site flexible acetonitrile molecular model is developed. The AMBER
      force field was used for description of intramolecular parameters, the atomic
      charges were calculated from a high level ab initio theory and finally the
      Lennard-Jones parameters were tuned to fit the experimental density and
      evaporation heat. The obtained in this way model reproduces correctly densities
      of water-acetonitrile mixtures as well as provides qualitative description of the
      dielectric permittivity and self-diffusion coefficients.

PMID- 17450555
TI  - A computational investigation on the sequential rearrangement mechanism of 2
      allyl-2,4,5-hexatrienaldehyde involving [1,5]-hydrogen migration and 8pi
      electrocyclization.
AB  - The sequential rearrangement reaction mechanism of the 2-allyl-2,4,5
      hexatrienaldehyde has been studied at the unrestricted Becke three-parameter
      hybrid functional combined with Lee-Yang-Parr correlation functional (UB3LYP)/6
      31G**, Complete Active Space Self-Consistent Field (CAS (8,8))/6-31G**,
      Configuration Interaction with Single and Double Excitations (CISD)//UB3LYP/6
      31G** and the second-order perturbation theory based on the CASSCF reference wave
      function (CASPT2)//CAS(8,8)/6-31G** levels. Two pathways have been found to be
      involved for this reaction. The first pathway includes four processes of the
      rotation of the C3--C4 single bond, the stepwise [2 + 2] cycloaddition, the [1,5]
      hydrogen migration, and the ring opening isomerization, while the second pathway
      undergoes only two processes of the [1,5]-hydrogen migration and the 8pi
      electrocyclization. The calculation results indicate that the second pathway is
      favorable, in good agreement with the recent experimental observation. The whole
      reaction is stepwise and strong exothermic.

PMID- 17450556
TI  - Theoretical study of the interaction between sodium ion and a cyclopeptidic
      tubular structure.
AB  - DFT calculations have been carried out to describe the pathway of a sodium ion
      along the stacking direction of a tubular structure set up by five cyclopeptidic
      units, which can be considered a suitable model of a hollow tubular structure of
      indefinite length. A lattice of points inside the tubular structure is defined
      and the DFT interaction energy values with a sodium ion are obtained. The data
      allow predicting a zigzag path of the ion inside the hosting structure.

PMID- 17450557
TI  - No interaction between the serotonin transporter polymorphism (5-HTTLPR) and
      childhood adversity or recent stressful life events on symptoms of depression:
      results from two community surveys.
AB  - In this study we investigated interactions between the 5-HTTLPR genotype and
      environmental risk factors (G x E) on symptoms of depression in two large
      Australian community samples of adolescents and young adults. We postulated that
      a significant interaction between the 5-HTTLPR genotype and environmental risk
      factors of childhood adversity or stressful life events on symptoms of depression
      would be observed in subjects with at least one short allele (s/l or s/s)
      compared with subjects with no short alleles (l/l). We did not find significant G
      x E interactions between the 5-HTTLPR genotype and recent stressful life events
      or childhood adversity on symptoms of depression in our sample populations.
      However, we did find adolescents aged 17-18 years homozygous for the long allele
      (l/l) and exposed to persistently high levels of family adversity over a 6-year
      period were at a greater risk of depression than subjects with the same genotype
      exposed to no or persistently low levels of family adversity. This interaction
      should be interpreted cautiously due to the small number of depressed subjects in
      the sample with persistently high levels of family adversity.

PMID- 17450558
TI  - Variance in facial recognition performance associated with BDNF in schizophrenia.

PMID- 17450559
TI  - And the segmentation clock keeps ticking.
AB  - The vertebrate body is organized in segments, easily visible in the consecutive
      vertebrae of the skeleton. These are first defined in the embryo by the formation
      of somites. Somites are generated at regular intervals from the presomitic
      mesoderm by a combination of oscillating signals, known as the segmentation
      clock, which establish the pace at which new somites are formed, and signaling
      gradients that set the location of new intersomitic borders. Using a microarray
      approach, Dequeant et al. have now shown that the segmentation clock is more
      complex than previously thought and includes oscillating expression of genes from
      at least three signaling pathways organized in coordinated networks.

PMID- 17450560
TI  - Social behavior and the evolution of neuropeptide genes: lessons from the
      honeybee genome.
AB  - Honeybees display a fascinating social behavior. The structural basis for this
      behavior, which made the bee a model organism for the study of communication,
      learning and memory formation, is the tiny insect brain. Neurons of the brain
      communicate via messenger molecules. Among these molecules, neuropeptides
      represent the structurally most-diverse group and occupy a high hierarchic
      position in the modulation of behavior. A recent analysis of the honeybee genome
      revealed a considerable number of predicted (200) and confirmed (100)
      neuropeptides in this insect. Is this quantity merely the result of advanced mass
      spectrometric techniques and bioinformatic tools or does it reflect the
      expression of more of these important messenger molecules, more than known from
      other insects studied so far? Our analysis of the data suggests that the social
      behavior is by no means correlated with a specific increase in the number of
      neuropeptides. Indeed, the honeybee genome is likely to contain fewer
      neuropeptide genes, neuropeptide paralogues and neuropeptide receptor genes than
      the solitary fruitfly Drosophila.

PMID- 17450561
TI  - Complete maps of molecular-loop conformational spaces.
AB  - This paper presents a numerical method to compute all possible conformations of
      distance-constrained molecular loops, i.e., loops where some interatomic
      distances are held fixed, while others can vary. The method is general (it can be
      applied to single or multiple intermingled loops of arbitrary topology) and
      complete (it isolates all solutions, even if they form positive-dimensional
      sets). Generality is achieved by reducing the problem to finding all embeddings
      of a set of points constrained by pairwise distances, which can be formulated as
      computing the roots of a system of Cayley-Menger determinants. Completeness is
      achieved by expressing these determinants in Bernstein form and using a numerical
      algorithm that exploits such form to bound all root locations at any desired
      precision. The method is readily parallelizable, and the current implementation
      can be run on single- or multiprocessor machines. Experiments are included that
      show the method's performance on rigid loops, mobile loops, and multiloop
      molecules. In all cases, complete maps including all possible conformations are
      obtained, thus allowing an exhaustive analysis and visualization of all pseudo
      rotation paths between different conformations satisfying loop closure.

PMID- 17450562
TI  - Algorithm to evaluate rate constants for polyatomic chemical reactions. II.
      Applications.
AB  - A new implementation of the classical reaction path-Liouville algorithm, as
      developed by the authors in the preceding paper, is tested with several chemical
      reactions. It results in a simple algorithm, which may be used straightforwardly
      for the calculation of rate constants, as well as to extract dynamical
      information of the reactive process. Results for the rate constant have been
      compared to transition state calculations, confirming that it provides a new
      lower bound than traditional transition state estimates. In addition, the time
      dependence of the kinetic energy stored in vibrational modes has been studied, as
      a means of characterizing the importance of each normal mode inside the reaction
      mechanism.

PMID- 17450563
TI  - Electronic structures and chemical bonding in 4d transition metal monohalides.
AB  - Bond distances, vibrational frequencies, dipole moments, dissociation energies,
      electron affinities, and ionization potentials of MX (XM = Y-Cd, X = F, Cl, Br,
      I) molecules in neutral, positively, and negatively charged ions were studied by
      density functional method, B3LYP. The bonding patterns were analyzed and compared
      with both the available data and across the series. It was found that besides
      ionic component, covalent bonds are formed between the 4d transition metal s, d
      orbitals, and the p orbital of halogen. For both neutral and charged molecules,
      the fluorides have the shortest bond distance, iodides the longest. Although the
      opposite situation is observed for vibrational frequency, that is, fluorides have
      the largest value, iodides the smallest. For neutral and anionic species, the
      dissociation energy tends to decrease with the increasing atomic number from Y to
      Cd, suggesting the decreasing or weakening of the bond strength. For cationic
      species, the trend is observed from Y to Ag.

PMID- 17450564
TI  - A combined electronegativity equalization and electrostatic potential fit method
      for the determination of atomic point charges.
AB  - We report an approach for the determination of atomic monopoles of macromolecular
      systems using connectivity and geometry parameters alone. The method is
      appropriate also for the calculation of charge distributions based on the quantum
      mechanically determined wave function and does not suffer from the mathematical
      instability of other electrostatic potential fit methods.

PMID- 17450565
TI  - Coarse-graining: a procedure to generate equilibrated and relaxed models of
      amorphous polymers.
AB  - We present a coarse-graining procedure to construct models of amorphous polymers.
      The method, which was applied to polyethylene, is based on a generation
      relaxation strategy previously developed to provide independent atomistic
      microstructures. The coarse-graining was performed by assigning positions to
      mesoscopic particles denoted blobs, which represent groups of atoms, through
      distance, angle and dihedral distribution functions. The interaction energy
      between pairs of blobs was evaluated through a soft potential, whose parameters
      were derived from atomistic models. Three levels of coarse-graining that differ
      in the number of atoms included in the blob have been considered. The structural
      and energy-related properties calculated using the coarse-grained models
      developed in this study are in good agreement with those obtained using atomistic
      simulations.

PMID- 17450566
TI  - NLOPredict: visualization and data analysis software for nonlinear optics.
AB  - A data analysis and visualization program was developed to assist in the
      interpretation of second-order nonlinear optical (NLO) processes, including
      vibrational sum-frequency generation and electronically resonant second harmonic
      generation. A novel diagrammatic approach allows concise visual representations
      of the resonant NLO molecular response. By mapping the predicted NLO response as
      a function of molecular orientation, molecular modeling results can be combined
      with experimental measurements for orientational analysis. A method is developed
      and implemented to predict the nonlinear optical properties of the amide
      backbones in complete proteins with known structures. NLOPredict is available for
      most computer operating systems from http://sda.iu.edu/nlopredict/.

PMID- 17450567
TI  - Inhibitor docking screened by the modified SAFE_p scoring function: application
      to cyclic urea HIV-1 PR inhibitors.
AB  - Our laboratory has in the past developed a method for the prediction of ligand
      binding free energies to proteins, referred to as SAFE_p (Solvent free energy
      predictor). Previously, we have applied this protocol for the prediction of the
      binding free energy of peptidic and cyclic urea HIV-1 PR inhibitors, whose X-ray
      structures bound to enzyme are known. In this work, we present the first account
      of a docking simulation, where the ligand conformations were screened and
      inhibitor ranking was predicted on the basis of a modified SAFE_p approach, for a
      set of cyclic urea-HIV-1 PR complexes whose structures are not known. We show
      that the optimal dielectric constant for docking is rather high, in line with the
      values needed to reproduce some protein residue properties, like pKa's. Our
      protocol is able to reproduce most of the observed binding ranking, even in the
      case that the components of the equation are not fitted to experimental data.
      Partition of the binding free energy into pocket and residue contributions sheds
      light into the importance of the inhibitor's fragments and on the prediction of
      "hot spots" for resistance mutations.

PMID- 17450568
TI  - New parallel algorithm for MP2 energy gradient calculations.
AB  - A new parallel algorithm has been developed for calculating the analytic energy
      derivatives of full accuracy second order Moller-Plesset perturbation theory
      (MP2). Its main projected application is the optimization of geometries of large
      molecules, in which noncovalent interactions play a significant role. The
      algorithm is based on the two-step MP2 energy calculation algorithm developed
      recently and implemented into the quantum chemistry program, GAMESS. Timings are
      presented for test calculations on taxol (C47H51NO14) with the 6-31G and 6-31G(d)
      basis sets (660 and 1032 basis functions, 328 correlated electrons) and luciferin
      (C11H8N2O3S2) with aug-cc-pVDZ and aug-cc-pVTZ (530 and 1198 basis functions, 92
      correlated electrons). The taxol 6-31G(d) calculations are also performed with up
      to 80 CPU cores. The results demonstrate the high parallel efficiency of the
      program.

PMID- 17450569
TI  - Computational chemistry comparison of stable/nonstable protein mutants
      classification models based on 3D and topological indices.
AB  - In principle, there are different protein structural parameters that can be used
      in computational chemistry studies to classify protein mutants according to
      thermal stability including: sequence, connectivity, and 3D descriptors.
      Connectivity parameters (called topological indices, TIs) are simpler than 3D
      parameters being then less computationally expensive. However, TIs ignore
      important aspects of protein structure and hence are expected to be inaccurate.
      In any case, a comparison of 3D and TIs has not been reported with respect to the
      power of discrimination of proteins according to stability. In this study, we
      compare both classes of indices in this sense by the first time. The best model
      found, based on 3D spectral moments correctly classified 507 out of 525 (96.6%)
      proteins while TIs model correctly classified 404 out of 525 (77.0%) proteins. We
      have shown that, in fact, 3D descriptor models gave more accurate results than
      TIs but interestingly, TIs give acceptable results in a timely way in spite of
      their simplicity.

PMID- 17450570
TI  - A molecular signature for the "master" heart cell.
AB  - The vertebrate heart comprises a variety of cell types, the majority of which are
      cardiomyocytes, smooth muscle and endothelial cells. Their origin is still an
      intriguing research topic and the question is whether these cells derive from a
      common or from multiple distinct progenitor cell(s). Three recent publications
      not only suggest the existence of a single progenitor cell that can give rise to
      cardiovascular lineages but additionally uncovered, at least in part, the
      molecular identity of such a multipotent precursor cell. These findings
      constitute major progress in the quest for stem-cell therapies for cardiac
      diseases.

PMID- 17450571
TI  - Extended binding site of ricin B lectin for oligosaccharide recognition.
AB  - The plant lectin ricin B chain binds oligosaccharide with more affinity than the
      mono- or disaccharide ligands. The experiments indicated that a biantennary
      oligosaccharide could bind itself to any of the crystallographically established
      1st or 2nd binding sites. After manual docking of either terminal galactose
      residues of the oligosaccharide in the 1st and 2nd binding sites of Ricin B and
      simulating the systems over nanosecond trajectories in implicit solvent, it was
      observed that the protein bound the oligosaccharide strongly through both its 1st
      and 2nd binding sites. Not only were the terminal galactose residues, several
      other residues of the oligosaccharide were involved in the binding scheme.
      Average gas phase energies were calculated molecular mechanically, solvation
      energies were calculated by Generalized Born model and the normal mode analysis
      was used to calculate the entropic contribution of binding. The entropy/enthalpy
      compensation has been observed for the protein-oligosaccharide interactions. The
      binding was found to be enthalpically favorable and compensating for the
      unfavorable entropic contribution. Comparison of the calculated free energy with
      the experimental data clearly suggests that binding is mono-dentate rather than
      bi-dentate through a single Gal-containing antenna.

PMID- 17450572
TI  - Influence of local and residual structures on the scaling behavior and dimensions
      of unfolded proteins.
AB  - Although recent spectroscopic studies of chemically denatured proteins hint at
      significant nonrandom residual structure, the results of extensive small angle X
      ray scattering studies suggest random coil behavior, calling for a coherent
      understanding of these seemingly contradicting observations. Here, we report the
      results of a Monte Carlo study of the effects of two types of local structures,
      alpha helix and Polyproline II (PPII) helix, on the dimensions of random coil
      polyalanine chains viewed as a model of highly denatured proteins. We find that
      although Flory's power law scaling, long regarded as a signature of random coil
      behavior, holds for chains containing up to 90% alpha or PPII helix, the absolute
      magnitude of the chain dimensions is sensitive to helix content. As residual
      alpha helix content increases, the chain contracts until it reaches a minimum
      radius at approximately 70% helix, after which the chain dimensions expand
      rapidly. With an alpha helix content of approximately 20%, corresponding to the
      Ramachandran probability of being in the helical basin, experimentally observed
      radii of gyration are recovered. Experimental radii are similarly recovered at an
      alpha helix content of approximately 87%, providing an explanation for the
      previously puzzling experimental finding that the dimensions of the highly
      helical methanol-induced unfolded state are experimentally indistinguishable from
      those of the helix-poor urea-unfolded state. In contrast, the radius of gyration
      increases monotonically with increasing PPII content, and is always more expanded
      than the dimensions observed experimentally. These results suggest that PPII is
      unlikely the sole, dominant preferred conformation for unfolded proteins.

PMID- 17450573
TI  - Testosterone and carotenoids: an integrated view of trade-offs between immunity
      and sexual signalling.
AB  - Allocation tradeoffs with the immune system can enforce honesty on sexual signals
      that act as indicators of individual quality. Such tradeoffs can be brought about
      by (1) the dual action of testosterone, which stimulates sexual signals but also
      suppresses immune functions, and/or (2) competition for carotenoids, which can be
      deposited as ornamental pigments or used as antioxidants in support of immune
      functions. Recent studies integrate these two mechanisms by showing that
      testosterone treatment in male birds upregulates circulating lipoproteins, plasma
      carriers for carotenoids, and increases bio-availability of carotenoids, which
      enhances carotenoid-based sexual coloration and immune responsiveness.

PMID- 17450575
TI  - Mineralization of radiation-crosslinked polyvinyl alcohol/polyvinyl pyrrolidone
      hydrogels.
AB  - A study of the calcification of the polyvinyl alcohol/polyvinyl pyrrolidone
      (PVA/PVP) hydrogels during their exposure to a calcium chloride solution or a
      simulated body fluid has been carried out. On the basis of the experiments, using
      a two-compartment permeation cell, the diffusion of calcium ions and their
      subsequent deposition in the hydrogels were elucidated. Steady-batch experiments
      were also performed to further elaborate the deposition pattern and the types of
      calcium deposits. It was demonstrated that Fick's second law of diffusion can
      describe the diffusion of calcium ions through PVA/PVP hydrogels at 310 K. The
      diffusion coefficient was determined to be (4.4+/-0.1)x10(-10) m2/s and the
      partition coefficient for the hydrogels was 0.06. Formation of calcium deposits
      was noticed taking place both on the surface and inside the hydrogels. The
      deposits formed on the surface have flake morphology, while the deposits inside
      the hydrogels are more like globular aggregates. Both types of deposits have been
      characterized as being comprised calcium and hydroxyl ion deficient apatites with
      chloride ions the most likely substituting species at the hydroxyl sites.

PMID- 17450576
TI  - Chondrocyte-alginate bioconstructs: a nuclear magnetic resonance relaxation
      study.
AB  - Proton nuclear magnetic resonance (NMR) relaxometry can give informations about
      hydrogel scaffold properties. As these properties can be modified with culture
      time and conditions according to scaffold biodegradability and new tissue
      biosynthesis, the aim of this research was to test the efficiency of this
      noninvasive NMR technique in the follow-up of 3D cultures for tissue engineering.
      The distributions of proton relaxation times T1 and T2 have been measured on
      cylindrical gel samples of different types of alginate, in the presence or
      absence of hyaluronate, in gels or bioconstructs with encapsulated chondrocytes
      cultured for 30 days in normal or reduced weight conditions. It was found that T2
      increases with the mannuronate/guluronate ratio in alginate samples and with the
      presence of hyaluronate. The distributions of both T1 and T2 result wider for
      bioconstructs cultured in normal gravity than for those cultured in reduced
      weight conditions. Neither cell growing nor collagen production but only GAG
      neosynthesis have been demonstrated in our experimental conditions. In
      conclusion, T2 is sensitive to the gel properties (possibly to the rigidity of
      macromolecular components). The homogeneity of bioconstructs can be monitored by
      the distribution of T1 and T2. We propose that nonspatially resolved NMR
      relaxometry can efficiently be used in monitoring tissue development in a
      biodegradable scaffold for tissue engineering.

PMID- 17450577
TI  - Phenotype and gene expression pattern of osteoblast-like cells cultured on
      polystyrene and hydroxyapatite with pre-adsorbed type-I collagen.
AB  - Hydroxyapatite and type-I collagen are major components of bone matrix. We
      compared phenotype and gene expression pattern of osteoblast-like cells cultured
      on HAp and HAp with pre-adsorbed type-I collagen from neutral solutions (HAp/NCs)
      with those of tissue culture grade polystyrene (TCPS) and TCPS with the collagen
      (TCPS/NCs). In initial cell attachment, the cells tensely spread on TCPS, while
      loosely spread on TCPS/NCs, HAp, and HAp/NCs. The levels of expressed integrin
      alpha2 and alpha5 subunits were not significantly different among any surfaces.
      Although the cells on HAp/NCs directly attached with the same collagen molecules
      as TCPS/NCs, mineralization was observed in only TCPS/NCs. The basal substrates
      (TCPS and HAp) greatly influenced osteoblast maturation even in the surfaces with
      pre-adsorbed collagen, since mineralization was induced by TCPS, but not by HAp.
      Gene expression pattern analyzed with DNA microarray also supported greater
      influence of basal substrates than pre-adsorbed collagen. In addition,
      comprehensive gene expression analyses revealed that HAp and HAp/NCs specifically
      up-regulated Ly6a and Tmem37 genes, while down-regulated Ifitm5 gene.

PMID- 17450578
TI  - Biodegradable fibrous scaffolds composed of gelatin coated poly(epsilon
      caprolactone) prepared by coaxial electrospinning.
AB  - A facile coaxial electrospinning technique was devised to prepare biodegradable
      core-shell fibrous scaffolds with poly(epsilon-caprolactone) (PCL) comprising the
      core structure and gelatin forming the coating of the fibers. The effect of the
      feed rate of the inner dope on the electrospinning process and fiber morphology
      was investigated. The results indicated that core-shell fibers with narrow size
      distribution and smooth surface morphology could be obtained when the feed rate
      was below 8 mL/h. An increase of the feed rate resulted in analogous increase in
      the diameters of both the inner PCL fiber core and the entire core-shell fibers.
      XPS analyses revealed that the surface of the core-shell fibers was tainted with
      a small amount of PCL. The outer gelatin layer in the core-shell fibers was
      crosslinked with glutaraldehyde. By optimizing the glutaraldehyde/gelatin feed
      ratio, crosslinked scaffolds with high porosity were obtained. The mechanic
      strength of the hydrated, crosslinked core-shell fibrous scaffolds was
      significantly enhanced because of the presence of hydrophobic PCL in the core
      region of the fibers. Results of cell culture studies suggested that the
      crosslinked, core-shell fibrous scaffold were nontoxic and capable of supporting
      fibroblast adhesion and proliferation.

PMID- 17450579
TI  - Biphasic hemodynamic responses influence deactivation and may mask activation in
      block-design fMRI paradigms.
AB  - A previous block-design fMRI study revealed deactivation in the hippocampus in
      the transverse patterning task, specifically designed, on the basis of lesion
      literature, to engage hippocampal information processing. In the current study, a
      mixed block/event-related design was used to determine the temporal nature of the
      signal change leading to the seemingly paradoxical deactivation. All positive
      activations in the hippocampal-dependent condition, relative to a closely matched
      control task, were seen to result from positive BOLD transients in the typical 4
      7 s poststimulus time range. However, most deactivations, including in the
      hippocampus and in other "default mode" regions commonly deactivated in cognitive
      tasks, were attributable to enhanced negative transient signals in a later time
      range, 10-12 s. This late hemodynamic transient was most pronounced in medial
      prefrontal cortex. In some regions, the hippocampal-dependent condition enhanced
      both the early positive and late negative transients to approximately the same
      degree, resulting in no significant signal change when block analysis is used,
      despite very different event-related responses. These results imply that delayed
      negative transients can play a role in determining the presence and sign of brain
      activation in block-design studies, in which case an event-related analysis can
      be more sensitive than a block analysis, even if the different conditions occur
      within blocks. In this case, default mode deactivations are timelocked to
      stimulus presentation as much as positive activations are, but in a later time
      range, suggesting a specific role of negative transient signals in task
      performance.

PMID- 17450580
TI  - Nano finite element modeling of the mechanical behavior of biocomposites using
      multi-scale (virtual internal bond) material models.
AB  - It is evident that biocomposites, specifically mineralized Type-I collagen
      fibrils, have strong mechanical properties, such as a desirable combination of
      elastic modulus, fracture toughness, and fracture strength. The mineral
      Hydroxyapatite [Hap] by itself is stiffer, and it is not clear whether a collagen
      fiber by itself has a lower breaking strength than the mineralized fiber. Hence,
      the objective of this paper is to develop, outline, apply, and demonstrate issues
      involving a new nano explicit finite element based framework, by which the
      mechanical behavior of mineralized collagen fibrils and their constituents can be
      studied. A multi-scale virtual internal bond model is used to model the material
      behavior and failure of such biocomposites. In this research two models have been
      studied. The first model attempts to illustrate the hypothesis that materials are
      less sensitive to flaws at nanoscale and the second model studies the mechanical
      behavior of a nano sized dahlite mineral crystal commonly found in collagen
      fibril. Two important implementation characteristics have been introduced and
      illustrated, namely that scaled properties can be used at the micro and nano
      length scales along with scaled dimensions and secondly the loading time can be
      appropriately scaled without the loading becoming a dynamic loading.

PMID- 17450581
TI  - Decrease in glucose metabolism in frontal cortex associated with deterioration of
      microstructure of corpus callosum measured by diffusion tensor imaging in healthy
      elderly.
AB  - The neural functions of signaling are carried out by the interconnection of
      neurons via neuronal fibers. Diffusion tensor imaging has recently become an
      established technique that enables the in vivo visualization of white matter (WM)
      fibers. Studies of normal aging have suggested the disruption of WM fiber
      microstructures with anterior-posterior gradient. Because neuronal activity is
      tightly coupled with glucose metabolism, neuronal death or a decrease in synaptic
      activity with aging may cause a decrease in glucose metabolism in the brain. We
      examined whether the disruption of callosal fiber microstructures in the healthy
      elderly is accompanied by changes in regional glucose metabolism (rMGlu) in the
      brain. Fifteen healthy volunteers in their seventies participated. Fractional
      anisotropies (FAs) of the genu and splenium of the corpus callosum (CC) were
      measured for each subject, and their correlations with rMGlu were analyzed using
      SPM2 software. We found a statistically significant positive correlation of rMGlu
      in the bilateral frontal cortices with the FA of the genu of the CC, whereas
      there was no correlation of the FA of the splenium of the CC and rMGlu. By voxel
      based morphometry, we found no decrease in gray matter concentration associated
      with FA. The results indicate that neuronal activity in the frontal cortices may
      decrease with the disruption of the microstructures of the CC without
      corresponding gray matter atrophy.

PMID- 17450582
TI  - The dynamic network subserving the three phases of cognitive procedural learning.
AB  - Cognitive procedural learning is characterized by three phases (cognitive,
      associative, and autonomous), each involving distinct processes. We performed a
      behavioral study and a positron emission tomography (PET) activation study using
      the Tower of Toronto task. The aim of the behavioral study was to determine
      cognitive predictors for the length of each of the three learning phases, in
      order to preselect subjects for the PET study. The objective of the second study
      was to describe the cerebral substrates subtending these three phases. Contrasted
      with a reference (motor) task, the cognitive phase activated the prefrontal
      cortex, cerebellum, and parietal regions, all of which became less active as
      learning progressed. The associative phase was characterized by the activation of
      the occipital regions, right thalamus, and caudate nucleus. During the autonomous
      phase, new regions were involved, including the left thalamus and an anterior
      part of the cerebellum. These results, by employing a direct comparison between
      phases, provide the first evidence of the involvement and the time course of
      activation of different regions in each learning phase, in accordance with
      current models of cognitive procedural learning. The involvement of a
      frontoparietal network suggests the use of strategies in problem solving during
      the cognitive phase. The involvement of the occipital regions during the
      associative and autonomous phase suggests the intervention of mental imagery.
      Lastly, the activation of the cerebellum during the autonomous phase is
      consistent with the fact that performance in this phase is determined by
      psychomotor abilities.

PMID- 17450583
TI  - Impedimetric sensing of cells on polypyrrole-based conducting polymers.
AB  - Polypyrrole (PPy) is a conducting polymer that may be electrochemically generated
      with the incorporation of any anionic species, including net-negatively charged
      biological molecules such as proteins and polysaccharides. In this article,
      dermatan and chloride-loaded PPy films were prepared on gold sputter-coated
      coverslips and various skin derived cells were studied on them by electrochemical
      impedance spectroscopy. Impedance spectra in the frequency range 1-100 kHz were
      either determined at specific times or impedance was monitored continuously at
      specific frequencies. An equivalent impedance circuit was fitted to the recorded
      impedance spectra to obtain parameters whose contributions could be mapped to
      intracellular and intercellular current pathways, and the membrane properties of
      cells. Results show cell-induced impedance changes were detected over PPy
      modified electrodes and were dependent on cell density and type, monitoring
      frequency, material composition, and treatment. Lower cell densities were
      detected on PPy when compared with bare gold. Keratinocyte confluence, as
      determined by impedimetric analysis, was reached more rapidly on PPy than on
      gold. This was consistent with previous, more cumbersome, biochemical assays.
      Electrical equivalent circuit analysis provided evidence that the technique may
      be extended to discriminate cell type because of the intracellular and
      intercellular resistance, and cell membrane capacitance being related to cell
      morphology.

PMID- 17450584
TI  - Substance P augments PGE2 and IL-6 production in titanium particles-stimulated
      fibroblasts from hip periprosthetic membrane.
AB  - Aseptic loosening remains the primary cause of failure in total joint
      arthroplasty. Implant-derived particles are thought to be a main cause of
      osteolysis that leads to failure of total joint arthroplasty. The nervous system
      has been implicated in the etiology and pathogenesis of joint diseases. Substance
      P (SP) immunoreactive nerve fibers have been detected in the pseudomembrane and
      pseudocapsular tissues of aseptic loose hip prostheses, suggesting that SP might
      be involved in the process of aseptic loosening. Fibroblasts are abundant in
      periprosthetic membrane. Neuropeptides are able to modulate cytokine production
      by fibroblasts. In this study, we isolated fibroblasts from periprosthetic
      membrane at the time of revision hip arthroplasty performed because of aseptic
      loosening. Fibroblasts were stimulated with titanium (Ti) particles or SP.
      Prostaglandin (PG) E2 and interleukin-6 (IL-6) assays were performed using enzyme
      linked immunosorbent assay kit. PGE2 and IL-6 secretion by fibroblasts have been
      significantly increased in the presence of Ti particles or SP. Moreover SP caused
      significant increase in PGE2 and IL-6 production by Ti particles-stimulated
      fibroblasts. Thus, SP and Ti particles acted synergistically to increase PGE2 and
      IL-6 secretion in fibroblasts from periprosthetic membrane.

PMID- 17450585
TI  - In vitro biocompatibility of degradable biopolymers in cell line cultures from
      various ocular tissues: direct contact studies.
AB  - Synthetic biodegradable polymers have many potential therapeutic applications. In
      ophthalmology, biodegradable polymers have been used as viscoelastic agents and
      surgical implants. Other potential applications include controlled release of
      drugs and growth factors, gene therapy, and tissue engineering. In the present
      study, in vitro biocompatibility of three biodegradable polymers, 50:50 PDLGA,
      85:15 PDLGA, and Inion GTR membrane was evaluated in comparison to tissue culture
      polystyrene by investigating cell proliferation and potential acute toxicity by
      the WST-1 cytotoxicity/cell proliferation test, the ATP test, and the lactate
      dehydrogenase (LDH) test. Evaluations were conducted with cell line cultures from
      various ocular tissues, human corneal epithelial cells (HCE), rabbit stromal
      fibroblasts (SIRC), bovine corneal endothelial cells (BCE), human conjunctival
      epithelial cells (IOBA-NHC), and human retinal pigment epithelial cells (ARPE-19)
      by direct contact studies by plating the cells on the polymer film specimens in
      96-wells. The proliferation results show that cell lines from various ocular
      tissues attached and grew on PDLGA 50:50, PDLGA 85:15, and Inion GTR membrane.
      Cytotoxicity experiments with the LDH and ATP tests showed no or extremely slight
      toxic adverse effects. These polymers have potential to be used as scaffolds in
      cell transplantation devices or as surgical implants.

PMID- 17450586
TI  - Quaternized chitosan/alginate nanoparticles for protein delivery.
AB  - Quaternized chitosan (QCS)/alginate (AL) nanoparticles (QCS/AL) were successfully
      prepared in neutral condition for the oral delivery of protein. The
      physicochemical structure of the QCS/AL nanoparticles was characterized by IR
      spectroscopy and transmission electron microscopy. The diameter of the
      nanoparticles with a positive surface charge was about 200 nm. The load of bovine
      serum albumin (BSA) was affected by the concentration and the molecular
      parameters, i.e. degree of substitution (DS) and weight-average molecular weight
      (Mw) of QCS, as well as the concentration of BSA. The release of BSA from
      nanoparticles was pH-dependent. Quick release occurred in 0.1M phosphate buffer
      solution (PBS, pH=7.4), while the release was slow in 0.1M HCl (pH=1.2). The DS
      and Mw of QCS play important roles in the release of BSA in vitro. QCS with high
      Mw accelerated the release of BSA in acid, while high DS retarded the release of
      BSA in both 0.1M HCl and 0.1M PBS.

PMID- 17450587
TI  - Food and drug administration expanded access to treatment: implications for
      oncology patients.

PMID- 17450588
TI  - Mosaic versus regulation development in avian blastoderms depends on the spatial
      distribution of Rauber's sickle material.
AB  - We describe how to prepare unincubated avian eggs to obtain a greater number of
      clearly visible Rauber's sickles for experimental embryology. After hemi
      sectioning of unincubated chicken (Gallus domesticus) blastoderms and cultivating
      both halves in vitro, two kinds of development can be discerned: (1) when the
      unincubated blastoderms were hemi-sectioned according to the plane of bilateral
      symmetry, going through the middle region of Rauber's sickle, we obtained two
      hemi-embryos (a left and a right one). Each contained a half primitive streak,
      localized at the cut edge (starting from the most median part of Rauber's sickle)
      giving rise to a half mesoblast mantle and half area vasculosa, thus indicating
      mosaic development (each part of the whole fertilized egg would be able to form
      independently on its own). (2) When the unincubated blastoderm is hemi-sectioned
      more obliquely, going through a more lateral part of Rauber's sickle (sickle
      horn), two complete bilaterally symmetrically miniature embryos will form,
      indicating the so-called regulation phenomena. We demonstrate that these two
      types of development are in reality due to the different spreading and
      concentration of Rauber's sickle tissue (containing gamma ooplasm) around the
      area centralis. Embryonic regulation thus must not be considered as a kind of
      totipotent regeneration capacity of isolated parts of the unincubated avian
      blastoderm, but depends on the spatial distribution of a kind of extraembryonic
      tissue (Rauber's sickle) built up by the oblique uptake of gamma ooplasm
      (ooplasmic mosaicism) at the moment of bilateral symmetrization (Callebaut [1994]
      Eur Arch Biol 105:111-123; Callebaut [2005] Dev Dyn 233:1194-1216).

PMID- 17450589
TI  - Role of diagnostic and ablative minimally invasive surgery for pediatric
      malignancies.
AB  - BACKGROUND: The use of minimally invasive surgery (MIS) in pediatric cancer is a
      matter of debate. The diagnostic and ablative roles of MIS were evaluated in a
      consecutive series of children with malignancies. METHODS: A prospective study,
      including all patients, who underwent abdominal and thoracic surgery for
      confirmed or highly suspected pediatric cancer was performed from September,
      2000, to December, 2005. An interdisciplinary panel approved the indication for
      minimally invasive or conventional surgery. RESULTS: At a single institution, 301
      operations were performed on 276 children with cancer. A minimally invasive
      approach was attempted in 90 of these patients (30%) and successfully employed in
      69 (77%) of the operations. However, 21 operations (23%) were converted to an
      open approach. Regarding the abdominal operations attempted laparoscopically, 41
      abdominal operations for biopsy or staging purposes were attempted
      laparoscopically (53%), but 6 were converted. In all, 139 abdominal resections
      were performed and 24 were attempted laparoscopically. Ten of these (42%) were
      converted. In 34 thoracic operations requiring biopsy, thoracoscopy was attempted
      in 14 (41%) and was successful in all but 1 (93%). Fifty-one thoracic tumors were
      resected and the thoracoscopic approach was attempted in 11 (22%) and successful
      in 7 (14%). Conversions from a minimally invasive operation to an open procedure
      occurred mainly due to limited visibility. Three bleeding complications occurred
      with 1 patient requiring a blood transfusion. In addition, 1 small bowel injury
      occurred with immediate laparoscopic closure. There were no port site recurrences
      after a median of 39 months. CONCLUSIONS: MIS is a reliable diagnostic tool for
      pediatric abdominal and thoracic malignancy. The role of ablative MIS in
      pediatric cancer remains limited.

PMID- 17450590
TI  - Prognostic factors of early distant recurrence in hormone receptor-positive,
      postmenopausal breast cancer patients receiving adjuvant tamoxifen therapy:
      results of a retrospective analysis.
AB  - BACKGROUND: Current adjuvant hormone therapy in postmenopausal women with breast
      cancer is debatable between upfront aromatase inhibitors (AIs) and sequential
      treatment with tamoxifen. A major concern is the higher rate of early recurrences
      observed with sequential treatment. The authors conducted a retrospective
      analysis to identify risk factors of early recurrences in hormone receptor (HR)
      positive, postmenopausal women within the first 3 years of adjuvant tamoxifen.
      METHODS: Between 1986 and 2000, operable breast cancer patients who received
      exclusively adjuvant tamoxifen for at least 3 years were selected from the
      authors' institutional database. Age, histology, pathologic tumor size, modified
      Scarff-Bloom-Richardson (mSBR) grade, mitotic index, tumor necrosis, peritumoral
      vascular emboli (PVE), HR status, and the number of involved axillary lymph-node
      were considered as prognostic factors of recurrence. RESULTS: Among 715 patients
      who met the inclusion criteria, a distant recurrence occurred in 38 patients
      (5.3%) within the first 3 years of tamoxifen therapy. Significant prognostic
      factors of early recurrence were mSBR, axillary lymph node involvement, tumor
      necrosis, mitotic index, PVE, and pathologic tumor size. Grade 1 and/or lymph
      node-negative tumors were excluded from the multivariate analysis (1 recurrence
      in 208 patients). In this model, mSBR grade 3 was the only significant predictive
      factor of early recurrence (hazard ratio, 3.72; P<.001). CONCLUSIONS: In this
      study, a subset of patients was identified that was at low-risk of early
      recurrence (mSBR grade 1 and/or negative lymph node status). Women in that subset
      could be treated using sequential hormone therapy with tamoxifen and AIs. In
      women with mSBR grade 3 or lymph node-positive tumors, an upfront treatment with
      AIs seemed to be the current optimal strategy.

PMID- 17450591
TI  - Economic burden of metastatic bone disease in the U.S.
AB  - BACKGROUND: Previous research has documented the prevalence of primary bone
      cancer; however, there are few data available regarding the impact of metastatic
      bone disease (MBD) on national expenditure. In this study, the authors quantified
      the prevalence and direct medical care costs of patients with MBD and the
      resulting cost impact on U.S. oncology expenditure. METHODS: Anonymous, patient
      level data on health care utilization and cost were obtained from the Thomson
      Medstat MarketScan research databases. In total, 396,200 patients who were
      diagnosed with cancer between 2000 and 2004 were selected for the study. Patients
      with MBD were matched subsequently to non-MBD controls. A 2-part linear
      regression model was used to compare cases with controls to quantify the
      incremental cost associated with the disease. RESULTS: Cancer prevalence in the
      U.S. during the study period was estimated at 4,861,987 cases annually, and 5.3%
      (n=256,137) of those patients had MBD. Rates of MBD were highest in patients with
      multiple myeloma (28.8%) and lung cancer (15.6%). The mean direct medical cost
      for all cancers combined was $75,329 for patients with MBD and $31,382 for
      controls. Regression-adjusted, incremental costs were $44,442 (P<.001) across all
      cancer types. The incremental cost was highest for patients with multiple myeloma
      ($63,455) and lowest for patients with lung cancer ($24,946). CONCLUSIONS: The
      national cost burden for patients with MBD was estimated at $12.6 billion, which
      is 17% of the $74 billion in total direct medical cost estimated by the National
      Institutes of Health, suggesting that MBD is a significant driver of overall
      oncology cost.

PMID- 17450592
TI  - Advances in molecular biology of hibernation in mammals.
AB  - Mammalian hibernation is characterized by profound reductions in metabolism,
      oxygen consumption and heart rate. As a result, the animal enters a state of
      suspended animation where core body temperatures can plummet as low as -2.9
      degrees C. Not only can hibernating mammals survive these physiological extremes,
      but they also return to a normothermic state of activity without reperfusion
      injury or other ill effects. This review examines recent findings on the genes,
      proteins and small molecules that control the induction and maintenance of
      hibernation in mammals. The molecular events involved with remodeling metabolism,
      inducing hypothermia and maintaining organ function are discussed and considered
      with respect to analogous processes in non-hibernating mammals such as mice and
      humans. The advent of sequenced genomes from three distantly related hibernators,
      a bat, hedgehog and ground squirrel, provides additional opportunities for
      molecular biologists to explore the mechanistic aspects of this biological
      adaptation in greater detail.

PMID- 17450593
TI  - Chiral discrimination via nuclear magnetic shielding polarisabilities from NMR
      spectroscopy: theoretical study of (R(a))-1,3-dimethylallene, (2R)-2
      methyloxirane, and (2R)-N-methyloxaziridine.
AB  - Three medium-size optically active molecules have been studied to make a guess at
      candidates suitable for chiral discrimination in an isotropic medium via nuclear
      magnetic resonance spectroscopy. The criterion for experimental detection is
      given by the magnitude of the isotropic part of nuclear magnetic shielding
      polarisability tensors, related to a pseudoscalar of opposite sign for the two
      enantiomers. The pseudoscalar shielding polarisability at the (17)O nucleus in N
      methyloxaziridine, calculated at the Hartree-Fock level, is approximately 7.8
      x10(-)(17) mV(-)(1). To obtain an experimentally observable magnetic field
      induced at the (17)O nucleus in N-methyloxaziridine, electric fields as large as
      approximately 10(7) - 10(8) Vm(-)(1) should be applied to the probe. The
      molecular electric dipole moment induced by precession of the magnetic dipole of
      the (17)O nucleus in a magnetic field of 10 T is, in absolute value,
      approximately 8.8 x 10(-)(42) Cm. The estimated rf-voltage at a resonance circuit
      is approximately 10 nV. Smaller values have been estimated for N, C, and H nuclei
      in 1,3-dimethylallene and 2-methyloxirane.

PMID- 17450594
TI  - Lentiviral nuclear import: a complex interplay between virus and host.
AB  - Although the capacity to infect non-dividing cells is a hallmark of lentiviruses,
      nuclear import is still barely understood. More than 100 research papers have
      been dedicated to this topic during the last 15 years, yet, more questions have
      been raised than answers. The signal-facilitating translocation of the viral
      preintegration complex (PIC) through the nuclear pore complex (NPC) remains
      unknown. It is clear, however, that nuclear import is the result of a complex
      interplay between viral and cellular components. In this review, we discuss the
      current knowledge on nuclear import. We focus on the controversies and pitfalls
      and discuss the interplay between virus and host.

PMID- 17450595
TI  - Collectins: sentinels of innate immunity.
AB  - Collectins, present in plasma and on mucosal surfaces, are humoral molecules of
      the innate immune system. They were discovered a hundred years ago in 1906 as the
      first association of an animal lectin with the immune system. They are a family
      of calcium-dependent lectins that recognize pathogen-associated molecular
      patterns. They share a similar modular domain architecture consisting of four
      regions; a cysteine-rich N-terminal domain, a collagen-like region, an alpha
      helical neck domain and a C-terminal carbohydrate recognition domain. There have
      been eight collectins members defined so far, of which, MBL, SP-A and SP-D are
      the most characterized. Collectins represent the first line of host defense. Upon
      recognition of the infectious agents, collectins put into action effector
      mechanisms like direct opsonization, neutralization, agglutination, complement
      activation and phagocytosis to curb the microbial growth. In addition, they also
      modulate inflammatory and allergic responses and apoptotic cell clearance. These
      functions limit infection and subsequently modulate the adaptive immune
      responses. The role of collectins, their structure, function, characteristics and
      clinical significance are reviewed in this article.

PMID- 17450596
TI  - Redox rhythmicity: clocks at the core of temporal coherence.
AB  - Ultradian rhythms are those that cycle many times in a day and are therefore
      measured in hours, minutes, seconds or even fractions of a second. In yeasts and
      protists, a temperature-compensated clock with a period of about an hour (30-90
      minutes) provides the time base upon which all central processes are
      synchronized. A 40-minute clock in yeast times metabolic, respiratory and
      transcriptional processes, and controls cell division cycle progression. This
      system has at its core a redox cycle involving NAD(P)H and dithiol-disulfide
      interconversions. It provides an archetype for biological time keeping on longer
      time scales (e.g. the daily cycles driven by circadian clocks) and underpins
      these rhythms, which cannot be understood in isolation. Ultradian rhythms are the
      foundation upon which the coherent functioning of the organism depends.

PMID- 17450597
TI  - A validated high-performance liquid chromatographic method for the determination
      of moclobemide and its two metabolites in human plasma and application to
      pharmacokinetic studies.
AB  - A rapid and sensitive reversed-phase high-performance liquid chromatographic
      method (RP-HPLC) with ultraviolet detection has been developed for the
      determination of moclobemide and its metabolites, p-chloro-N-(-2
      morpholinoethyl)benzamide N'-oxide (Ro 12-5637) and p-chloro-N-[2-(3
      oxomorpholino)ethyl]-benzamide (Ro 12-8095), in human plasma. The assay was
      performed after single liquid-liquid extraction with dichloromethane at alkaline
      pH using phenacetin as the internal standard. Chromatographic separation was
      performed on a C(18) column using a mixture of acetonitrile and water (25:75,
      v/v), adjusted to pH 2.7 with ortho-phosphoric acid, as mobile phase.
      Spectrophotometric detection was performed at 239 nm. The method has been
      validated for accuracy, precision, selectivity, linearity, recovery and
      stability. The quantification limit for moclobemide and Ro 12-8095 was 10 ng/mL,
      and for Ro 12-5637 was 30 ng/mL. Linearity of the method was confirmed for the
      range 20-2500 ng/mL for moclobemide (r = 0.9998), 20-1750 ng/mL for Ro 12-8095 (r
      = 0.9996) and 30-350 ng/mL for Ro 12-5637 (r = 0.9991). Moreover, within-day and
      between-day precisions and accuracies of the method were established. The
      described method was successfully applied in pharmacokinetic studies of parent
      drug and its two metabolites after a single oral administration of 150 mg of
      moclobemide to 20 healthy volunteers.

PMID- 17450598
TI  - The size and form of chromosomes are constant in the nucleus, but highly variable
      in bacteria, mitochondria and chloroplasts.
AB  - From cytological examination, the size and form of the chromosomes in the
      eukaryotic nucleus are invariant across generations, leading to the expectation
      that constancy of inheritance likely depends on constancy of the chromosomal DNA
      molecule conveying the constant phenotype. Indeed, except for rare mutations,
      major phenotypic traits appear largely without change from generation to
      generation. Thus, when it was discovered that the inheritance of traits for
      bacteria, mitochondria and chloroplasts was also constant, it was assumed that
      chromosomes in those locations were also constant. Such has not turned out to be
      the case, however; those chromosomes are highly variable in structure. I propose,
      therefore, that only for the nucleus is there a requirement that a chromosome be
      "finished" (contain only fully replicated genomes) before it may segregate to
      daughter cells. This requirement does not apply to the variable chromosomes among
      chloroplasts, mitochondria and bacteria.

PMID- 17450599
TI  - The potential for the formation of the arginine biosynthetic enzymes and its
      masking during evolution.
AB  - The present account spans the history of arginine regulation from its discovery
      in 1955 until the present. In 1957 I demonstrated that not only added arginine
      but also internally produced arginine represses enzyme formation and that the
      potential for enzyme synthesis is in excess of what is required for growth. In
      1959 I located the regulatory gene argR encoding the arginine repressor. An
      unusual feature of this research was the finding that in E. coli B, in contrast
      to E. coli K12, arginine synthesis is permanently repressed, independent of
      arginine. This was due to a single amino acid difference between the two
      repressors. Recent studies showed that, in natural populations of E. coli, K12
      type regulation is much more frequent than B-type regulation, and that E. coli B
      evolved from a strain with K12-type regulation. In competition experiments, E.
      coli K12 was found to be favored in the presence of arginine and E. coli B in its
      absence, showing that contrary to expectations permanently turned off regulation
      is favored over negative regulation in some environments.

PMID- 17450601
TI  - Did the Dravidian speakers originate in Africa?

PMID- 17450600
TI  - Mity model: Tetranychus urticae, a candidate for chelicerate model organism.
AB  - Chelicerates (scorpions, horseshoe crabs, spiders, mites and ticks) are the
      second largest group of arthropods and are of immense importance for fundamental
      and applied science. They occupy a basal phylogenetic position within the phylum
      Arthropoda, and are of crucial significance for understanding the evolution of
      various arthropod lineages. Chelicerates are vectors of human diseases, such as
      ticks, and major agricultural pests, such as spider mites, thus this group is
      also of importance for both medicine and agriculture. The developmental genetics
      of chelicerates is poorly understood and a challenge for the future progress for
      many aspects of chelicerate biology is the development of a model organism for
      this group. Toward this end, we are developing a chelicerate genetic model: the
      two-spotted spider mite Tetranychus urticae. T. urticae has the smallest genome
      of any arthropod determined so far (75 Mbp, 60% of the size of the Drosophila
      genome), undergoes rapid development and is easy to maintain in the laboratory.
      These features make T. urticae a promising reference organism for the
      economically important, poorly studied and species-rich chelicerate lineage.

PMID- 17450603
TI  - Testing hypotheses without considering predictions.

PMID- 17450605
TI  - Calsenilin is required for endocrine pancreas development in zebrafish.
AB  - Calsenilin/DREAM/Kchip3 is a neuronal calcium-binding protein. It is a
      multifunctional protein, mainly expressed in neural tissues and implicated in
      regulation of presenilin processing, repression of transcription, and modulation
      of A-type potassium channels. Here, we performed a search for new genes expressed
      during pancreatic development and have studied the spatiotemporal expression
      pattern and possible role of calsenilin in pancreatic development in zebrafish.
      We detected calsenilin transcripts in the pancreas from 21 somites to 39 hours
      postfertilization stages. Using double in situ hybridization, we found that the
      calsenilin gene was expressed in pancreatic endocrine cells. Loss-of-function
      experiments with anti-calsenilin morpholinos demonstrated that injected morphants
      have a significant decrease in the number of pancreatic endocrine cells.
      Furthermore, the knockdown of calsenilin leads to perturbation in islet
      morphogenesis, suggesting that calsenilin is required for early islet cell
      migration. Taken together, our results show that zebrafish calsenilin is involved
      in endocrine cell differentiation and morphogenesis within the pancreas.

PMID- 17450606
TI  - Dark-red O(8) molecules in solid oxygen: rhomboid clusters, not S(8)-like rings.

PMID- 17450607
TI  - A synthetic supramolecular construct modulating protein assembly in cells.

PMID- 17450608
TI  - Porphine dimeric assemblies in organic-pillared coordination cages.

PMID- 17450609
TI  - Self-assembled hybrid oligo(p-phenylenevinylene)-gold nanoparticle tapes.

PMID- 17450610
TI  - Diastereoselective reductive amination of aryl trifluoromethyl ketones and alpha
      amino esters.

PMID- 17450612
TI  - Evaporation-induced self-assembly of nanoparticles from a sphere-on-flat
      geometry.

PMID- 17450611
TI  - Concave tetrathiafulvalene-type donors as supramolecular partners for fullerenes.

PMID- 17450613
TI  - A remarkably simple and efficient benzannulation reaction.

PMID- 17450614
TI  - Light-driven supramolecular chirality in propeller-like hydrogen-bonded complexes
      that show columnar mesomorphism.

PMID- 17450615
TI  - A way to highly enantiomerically enriched aza-Morita-Baylis-Hillman-type
      products.

PMID- 17450616
TI  - Designing paramagnetic circulenes.

PMID- 17450617
TI  - Rate-accelerated nonconventional amide synthesis in water: a practical catalytic
      aldol-surrogate reaction.

PMID- 17450618
TI  - The sulfhydryl radical (HS(.)/S(.-)): a contender for the isomerization of double
      bonds in membrane lipids.

PMID- 17450623
TI  - Antidepressants and psychosis in Parkinson disease: a case series.

PMID- 17450624
TI  - Minimalist active-site redesign: teaching old enzymes new tricks.
AB  - Although nature evolves its catalysts over millions of years, enzyme engineers
      try to do it a bit faster. Enzyme active sites provide highly optimized
      microenvironments for the catalysis of biologically useful chemical
      transformations. Consequently, changes at these centers can have large effects on
      enzyme activity. The prediction and control of these effects provides a promising
      way to access new functions. The development of methods and strategies to explore
      the untapped catalytic potential of natural enzyme scaffolds has been pushed by
      the increasing demand for industrial biocatalysts. This Review describes the use
      of minimal modifications at enzyme active sites to expand their catalytic
      repertoires, including targeted mutagenesis and the addition of new reactive
      functionalities. Often, a novel activity can be obtained with only a single point
      mutation. The many successful examples of active-site engineering through minimal
      mutations give useful insights into enzyme evolution and open new avenues in
      biocatalyst research.

PMID- 17450626
TI  - Slice and dice your way to better health. It's easy to get your five daily
      servings of vegetables when you integrate chopped, sliced and grated veggies into
      your meals.

PMID- 17450625
TI  - 6-Substituted pyrrolo[3,4-c]pyrazoles: an improved class of CDK2 inhibitors.
AB  - We have recently reported a new class of CDK2/cyclin A inhibitors based on a
      bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. The introduction of small
      alkyl or cycloalkyl groups in position 6 of this scaffold allowed variation at
      the other two diversity points. Conventional and polymer-assisted solution phase
      chemistry provided a way of generating compounds with improved biochemical and
      cellular activity. Optimization of the physical properties and pharmacokinetic
      profile led to a compound which exhibited good efficacy in vivo on A2780 human
      ovarian carcinoma.

PMID- 17450627
TI  - Ask the doctors. I recently read that patients with coronary artery disease ought
      to have their blood pressure reduced to less than 120/80. I thought 120/80 was
      normal blood pressure, so why would you want blood pressure to be lower than
      normal?

PMID- 17450628
TI  - Ask the doctors. My doctor said I have a lot of th risk factors for heart
      disease. He told me to lose weight and watch what I eat. He also started me on
      medications for blood pressure and high cholesterol. Why not wait to see if the
      weight loss helps before starting the meds?

PMID- 17450629
TI  - Putting excellence at the heart of European research.

PMID- 17450630
TI  - Expanding the RNA tool box.

PMID- 17450631
TI  - [A review of methods for the assessment of symptom validity: an update 2002 to
      2005].
AB  - Continuing a previous review on problems and strategies for the assessment of
      negative response bias (Fortschr Neurol Psychiatr 2002;70:126-138), an update on
      research published from 2002 to 2005 is provided. More than 400 journal articles
      were included in the analysis, It was found that symptom validity tests or effort
      tests are generally accepted as the one method which is best developed for the
      assessment of negative response bias. Other methods, including questionnaires and
      rating methods, are reviewed. Three important applications of symptom validity
      assessment are analysed in some more detail: retrograde amnesia, post-traumatic
      stress disorder, and pain. --Research activities in the field of what was
      previously called "malingering research" have not decreased, so further important
      developments can be expected in the years to come.

PMID- 17450632
TI  - [Romberg: a biographical sketch].
AB  - Moritz Heinrich Romberg can be considered the most important founder of clinical
      neurology as well as a significant reformer in medicine. In the present treatise
      his life, his oeuvres and his prominent scientific contributions are summarized
      with newly discovered photos, portraits and documents. A previously unknown
      Daguerreotype of him should be of particular interest. Romberg's significance and
      his accomplishments as an internationally renowned figure in medical history are
      emphasized.

PMID- 17450633
TI  - Oocyte donation for stem cell research.

PMID- 17450634
TI  - [Some corrections concerning vaccines campaigns].

PMID- 17450635
TI  - [The electroshock has disappeared].

PMID- 17450636
TI  - Where have all the MTs gone.

PMID- 17450637
TI  - More on Terre Cassee project.

PMID- 17450639
TI  - Promote midwifery.

PMID- 17450638
TI  - Midwives for Haiti.

PMID- 17450640
TI  - Efficacy of calculus removal from furcations using a Fissurotomy Bur in vitro.

PMID- 17450641
TI  - Interference and negative priming effects in adolescents with attention deficit
      hyperactivity disorder.
AB  - Three visual selective attention tasks were used to measure potential differences
      in susceptibility to interference and inhibitory cognitive control processes in
      16 adolescents diagnosed with attention deficit hyperactivity disorder (ADHD) and
      45 similar-aged controls. Susceptibility to interference was assessed using the
      Stroop color and word naming test. Efficiency of distractor inhibition was
      assessed in two conceptual negative priming tasks. The majority of studies in
      this area indicate that people with ADHD demonstrate higher levels of
      interference and lower negative priming effects in comparison with age-matched
      peers. However, we found that although the ADHD group was consistently slower to
      name target stimuli than the control group, there were no differences in
      interference or negative priming between the two groups.

PMID- 17450642
TI  - Locomotor training using body weight support on a treadmill improves mobility in
      persons with multiple sclerosis: a pilot study.
AB  - RATIONALE: The purpose of this protocol was to investigate the potential benefits
      and tolerability of locomotor training using body weight support on a treadmill
      (LTBWST) in persons with multiple sclerosis (MS). METHODS: Four persons with
      primarily spinal cord MS and severely impaired ambulation (Expanded Disability
      Status Scale score 7.0-7.5) were enrolled in LTBWST. Subjects completed an
      average of 40 training sessions over several months. RESULTS: Subjects showed
      improvement in muscle strength, spasticity, endurance, balance, walking speed,
      and quality of life at the end of the training sessions, and could tolerate
      training without fatigue or other adverse effects. CONCLUSIONS: LTBWST is well
      tolerated by persons with MS and may produce improvements in parameters related
      to functional mobility.

PMID- 17450643
TI  - Hospital land versus the real world.

PMID- 17450645
TI  - Pressure ulcer stages revised by the National Pressure Ulcer Advisory Panel.

PMID- 17450644
TI  - Healthcare logies take on pressure ulcers.

PMID- 17450646
TI  - Guide to outcomes instruments for musculoskeletal trauma research.

PMID- 17450647
TI  - Emerging from the shadow of Vioxx.

PMID- 17450648
TI  - Synergism of toxicity of N,N-diethyl-m-toluamide to German cockroaches
      (Orthoptera: Blattellidae) by hydrolytic enzyme inhibitors.
AB  - Various compounds were tested for effects on the toxicity of the insect repellent
      N, N-diethyl-m-toluamide (DEET) in German cockroaches, Blattella germanica (L.).
      Organophosphate and carbamate acetylcholinesterase inhibitors carbaryl, DEF,
      eserine (physostigmine, malathion and pyridostigmine bromide synergized DEET
      toxicity also synergized the toxicity of the formamidine pesticides. Amitraz and
      chlordimeform. Results suggest that DEET may have some toxic actions that are
      similar to those of formamidine pesticides. DEET synergized the toxicity of some
      acetylcholinesterase inhibitors but not others. Results further suggest that some
      mechanism other than acetylcholinesterase inhibition was responsible for the
      toxic interactions observed between DEET and the acetylcholinesterase inhibitors.

PMID- 17450649
TI  - Traumatic injury protection rider to Servicemembers' Group Life Insurance. Final
      rule.
AB  - This document adopts with changes a Department of Veterans Affairs (VA) interim
      final rule that implemented section 1032 of Public Law 109-13, the "Emergency
      Supplemental Appropriations Act for Defense, the Global War on Terror, and
      Tsunami Relief, 2005." Section 1032 of Public Law 109-13 established an automatic
      traumatic injury protection rider to Servicemembers' Group Life Insurance (SGLI)
      for any SGLI insured who sustains a serious traumatic injury that results in
      certain losses as prescribed by the Secretary of Veterans Affairs in
      collaboration with the Secretary of Defense. Section 1032(a) is codified at 38
      U.S.C. 1980A. Section 1032(c)(1) of Public Law 109-13 also authorized the payment
      of this traumatic injury benefit (TSGLI) to members of the uniformed services who
      incurred a qualifying loss between October 7, 2001, and the effective date of
      section 1032 of Public Law 109-13, i.e., December 1, 2005, provided the loss was
      a direct result of injuries incurred in Operation Enduring Freedom (OEF) or
      Operation Iraqi Freedom (OIF). This document modifies Sec. 9.20 of the interim
      rule to provide that a service member must suffer a scheduled loss within 2 years
      after a traumatic injury, rather than one year as provided in current Sec.
      9.20(d)(4). This document also amends Sec. 9.20(d)(1) to clarify that a service
      member does not have to be insured under SGLI in order to be eligible for TSGLI
      based upon incurrence of a traumatic injury between October 7, 2001, and December
      1, 2005, if the member's loss was a direct result of injuries incurred in OEF or
      OIF.

PMID- 17450650
TI  - Medical: informed consent--designate health care professionals to obtain informed
      consent. Final rule.
AB  - This document amends U.S. Department of Veterans Affairs (VA) medical regulations
      on informed consent. The final rule authorizes VA to designate additional
      categories of health care professionals to obtain the informed consent of
      patients or their surrogates for clinical treatment and procedures and to sign
      the consent form.

PMID- 17450651
TI  - Generalized anxiety disorder: raising the expectations of treatment.
AB  - Anxiety disorders are prevalent and associated with an increase in morbidity and
      mortality, particularly when present with additional psychiatric disorders. They
      represent a public health and economic burden, yet they are commonly
      underrecognized and undertreated. Benzodiazepines are effective anxiolytics, but
      they primarily treat the somatic symptoms of generalized anxiety disorder (GAD),
      and are not effective in treating the depressive symptoms that are often comorbid
      in chronic anxiety disorders like GAD. Some antidepressants may therefore offer
      the best choice of therapy. Their benefit in the treatment of GAD has been
      demonstrated using the tricyclic antidepressant, imipramine, and some selective
      serotonin reuptake inhibitors. The serotonin and norepinephrine reuptake
      inhibitor venlafaxine extended release (XR), has been indicated for GAD and has
      proven to be effective in both the short- and long-term treatment of patients
      with this disorder. Many patients treated with venlafaxine XR achieve and sustain
      remission from the symptoms of GAD, which is the goal of treatment.

PMID- 17450653
TI  - Organ procurement and transplantation network. Final rule.
AB  - This Final Rule sets forth the Secretary's decision to include intestines within
      the definition of organs covered by the regulations governing the operations of
      the Organ Procurement and Transplantation Network. The Secretary under the
      authority granted by section 301 of the National Organ Transplant Act, as
      amended, further effects a corresponding change to the definition of human organs
      covered in the statute with this Final Rule.

PMID- 17450652
TI  - [Aquaculture in Italy. An integrated model of product quality control].
AB  - Aquaculture is becoming increasingly diffuse even in Italy. The increased
      production introduces new problems such as product quality control and process
      safety. This article presents the results of a research project, funded by the
      Ministry of the Environment, whose aim was to evaluate and promote aquaculture
      product quality and safety in an environmentally responsible way. Four intensive
      land-based and offshore aquaculture sites were monitored to evaluate
      microbiological, biological and chemical (i.e. polychlorinated biphenyls and
      endocrine disruptors) quality of water, products and fish feed. In total 154
      samples were analysed, of which 66 were water samples, 55 product samples and 33
      feed samples. Salmonella and other enteric pathogens were absent in products and
      the aquatic environment, while other environmental pathogens of the Vibrio
      species were detected. Bacterial load and fecal indicators were found to be
      higher in off-shore products and in mussels from all aquaculture sites. PCBs were
      detected in all products in concentrations below 2 microg/g fresh product (Food
      and Drug Administration), but on average, higher concentrations were detected in
      off-shore products. No estrogen mimetic activity was detected in fish feed, in
      contrast it was detected in offshore products and water. Product quality was
      found to be strictly correlated with the quality of the environment. Genetically
      modified organisms were detected in fish feed but no integration of genetic
      material in products occurred.

PMID- 17450654
TI  - Disclosure of children's free and reduced price meals and free milk eligibility
      information in the child nutrition programs. Final rule.
AB  - This final rule establishes requirements for the disclosure of children's free
      and reduced price meals or free milk eligibility information under the Child
      Nutrition Programs. The Child Nutrition Programs include the National School
      Lunch Program, School Breakfast Program, Special Milk Program, Summer Food
      Service Program, and Child and Adult Care Food Program. Within certain
      limitations, children's free and reduced price meal or free milk eligibility
      information may be disclosed, without parental/guardian consent, to persons
      directly connected to certain education programs, health programs, means-tested
      nutrition programs, the Comptroller General of the United States, and some law
      enforcement officials. Additionally, officials also may disclose children's free
      and reduced price meal or free milk eligibility information to persons directly
      connected with State Medicaid (Medicaid) and the State Children's Health
      Insurance Program (SCHIP) when parents/guardians do not decline to have their
      information disclosed. These regulations affect State agencies and local program
      operators that administer the Child Nutrition Programs and households which apply
      for and/or are approved for free and reduced price meals or free milk. The final
      rule reflects the disclosure provisions of the Healthy Meals for Healthy
      Americans Act of 1994 and comments received on the proposed rule published in
      anticipation of implementing those provisions. Additionally, this final rule
      includes the regulatory disclosure provisions implementing the Agricultural Risk
      Protection Act of 2000 and comments received on the interim rule issued to
      implement those provisions. This final rule also implements nondiscretionary
      provisions of the Child Nutrition and WIC Reauthorization Act of 2004, allowing
      certain third party contractors access to children's eligibility status and will
      allow school officials to communicate with Medicaid and SCHIP officials to verify
      that children are eligible for free and reduced price school meals or free milk.
      The disclosure provisions are intended to reduce paperwork for administrators of
      certain programs that target low-income households and for low-income households
      which may benefit from those programs by allowing some sharing of household's
      free and reduced price meal eligibility information. This rule also includes
      several technical amendments.

PMID- 17450655
TI  - Blood vessels recovered with organs and intended for use in organ
      transplantation. Final rule.
AB  - The Food and Drug Administration (FDA) and the Health Resources and Services
      Administration (HRSA) are amending their regulations to include as part of an
      organ those blood vessels recovered with the organ that are intended for use in
      organ transplantation (HRSA regulation); and to exclude such blood vessels from
      the definition of human cells, tissues, or cellular or tissue-based products
      (HCT/Ps) (FDA regulation). The purpose of this final rule is to amend the
      regulations so that blood vessels recovered with organs and intended for use in
      organ transplantation, and labeled as such, are governed by the regulations
      pertaining to organs. The regulation of other recovered blood vessels remains
      unchanged. We (HRSA and FDA) believe that this change will eliminate the burden
      resulting from an organ procurement organization's efforts to comply with both
      FDA and HRSA rules with respect to blood vessels (FDA jurisdiction) and organs
      (HRSA jurisdiction).

PMID- 17450656
TI  - Exemption of chemical mixtures. Final rule.
AB  - On December 15, 2004, the Drug Enforcement Administration (DEA) published a Final
      Rule corrected January 4, 2005) that implemented new regulations concerning
      chemical mixtures that contain any of the 27 listed chemicals. The Final Rule
      added a new provision not previously raised by DEA in any proposed rulemaking.
      This newly introduced provision exempted domestic and import transactions in
      chemical mixtures that are regulated solely due to the presence of the List II
      solvent chemicals acetone, ethyl ether, 2-butanone, or toluene from the
      Controlled Substances Act (CSA) recordkeeping and reporting requirements. Because
      this exemption was not previously proposed in any rulemaking, DEA implemented
      this exemption on an interim basis and requested public comment on this exemption
      provision. Based upon a review of all comments, DEA is finalizing this exemption.
      As such, domestic and import transactions in chemical mixtures containing the
      List II chemicals acetone, ethyl ether, 2-butanone, and toluene shall be exempt
      from CSA chemical recordkeeping and reporting requirements.

PMID- 17450657
TI  - Sir William Bowman (1816-1892).

PMID- 17450658
TI  - Sir Stewart Duke-Elder (1898-1978).

PMID- 17450659
TI  - [AIDS control and prevention].

PMID- 17450660
TI  - Schedule for rating disabilities; Appendices A, B, and C. Final rule.
AB  - The Department of Veterans Affairs (VA) is revising its Schedule for Rating
      Disabilities, Appendices A, B, and C to include all current diagnostic codes.
      Appendix A is also amended to include all the diagnostic code historical
      information since the last review.

PMID- 17450661
TI  - Medicare program; physicians' referrals to health care entities with which they
      have financial relations (Phase II); continuation of effectiveness and extension
      of timeline for publication of final rule. Interim final rule; continuation of
      effectiveness and extension of timeline for publication of final rule.
AB  - This notice announces the continuation of effectiveness of a Medicare interim
      final rule and the extension of the timeline for publication of the final rule.
      This notice is issued in accordance with section 1871(a)(3)(C) of the Social
      Security Act (the Act), which allows an interim final rule to remain in effect
      after the expiration of the timeline specified in section 1871(a)(3)(B) of the
      Act if the Secretary publishes a notice of continuation prior to the expiration
      of the timeline.

PMID- 17450662
TI  - Vocational rehabilitation and Employment program--initial evaluations. Final
      rule.
AB  - The Department of Veterans Affairs (VA) adopts as a final rule in this document a
      proposed rule concerning initial evaluations of individuals who apply for
      vocational rehabilitation and employment benefits. This final rule is intended to
      reflect changes in law regarding initial evaluations, to reflect VA's
      interpretation of applicable law and its determinations of procedures appropriate
      for use in the initial evaluation, and to improve readability.

PMID- 17450663
TI  - Crossing the scales. Interview by Rebecca Gillan.

PMID- 17450664
TI  - Laxative drug products for over-the-counter human use; psyllium ingredients in
      granular dosage forms. Final rule.
AB  - The Food and Drug Administration (FDA) is issuing a final rule establishing that
      over-the-counter (OTC) laxative drug products in granular dosage form containing
      the bulk-forming psyllium ingredients (psyllium (hemicellulose), psyllium
      hydrophilic mucilloid, psyllium seed, psyllium seed (blond), psyllium seed husks,
      plantago ovata husks, and plantago seed) are not generally recognized as safe and
      effective (GRASE) and are misbranded. This final rule includes, but is not
      limited to, any granules that are swallowed dry prior to drinking liquid;
      dispersed, suspended, or partially dissolved in liquid prior to swallowing;
      chewed, partially chewed, or unchewed, and then washed down (or swallowed) with
      liquid; or sprinkled over food. FDA is issuing this final rule after considering
      reports of esophageal obstruction associated with the use of psyllium laxatives
      in granular dosage form. These cases continue to occur despite efforts to promote
      safe use through label warnings and directions. This final rule does not apply to
      psyllium laxatives in nongranular dosage forms, such as powders, tablets, or
      wafers. This final rule is part of FDA's ongoing review of OTC drug products.

PMID- 17450665
TI  - [To understand the words of cancer: Lexonco, dictionary of oncology SOR SAVOIR
      PATIENT for patients and relatives. Methodological aspects].
AB  - In response to the evolution of the information-seeking behaviour of patients and
      concerns from health professionals regarding cancer patient information, the
      French National Federation of Comprehensive Cancer Centres (FNCLCC) introduced,
      in 1998, an information and education program dedicated to patients and
      relatives, the SOR SAVOIR PATIENT program. Lexonco project is a dictionary on
      oncology adapted for patients and relatives and validated by medical experts and
      cancer patients. This paper describes the methodological aspects which take into
      account patients and experts' perspectives to produce the defi nitions.

PMID- 17450666
TI  - Medicare program; hospital conditions of participation: requirements for approval
      and re-approval of transplant centers to perform organ transplants. Final rule.
AB  - This final rule establishes, for the first time, Medicare conditions of
      participation for heart, heart-lung, intestine, kidney, liver, lung, and pancreas
      transplant centers. This rule sets forth clear expectations for safe, high
      quality transplant service delivery in Medicare-participating facilities. In
      addition, in this rule we respond to public comments on the proposed rule.

PMID- 17450667
TI  - Rural enrollment in Medicare advantage is concentrated in private fee-for-service
      plans.
AB  - Enrollment in Medicare Advantage (MA) plans more than doubled in rural areas in
      2006, the first year of the MA program. However, rural enrollment remains well
      below urban enrollment as a percentage of the eligible population. This policy
      brief provides findings about enrollment in the newly designed MA program in
      rural and urban areas across the United States and updates previous findings
      published in RUPRI Center policy briefs. Analysis of rural-urban differences in
      costs to beneficiaries that compares type of plan will be released in a policy
      brief in June 2007.

PMID- 17450668
TI  - The doctor won't see you now: rights of transgender adolescents to sex
      reassignment treatment.

PMID- 17450669
TI  - The asthma crisis in low-income communities of color: using the law as a tool for
      promoting public health.

PMID- 17450670
TI  - [The French National Authority for Health].
AB  - The French National Authority of Health (HAS) is an independent and scientific
      public body assessing healthcare technologies and procedures for reimbursement
      and pricing. It also produces tools (guidelines, certificates, agreements and
      labels) designed to help healthcare professionals provide treatments of better
      quality and efficiency.

PMID- 17450671
TI  - [The Direction Generale de la Sante today].
AB  - The Direction generale de la sante, created fifty years ago as part of the French
      Ministry of Health, is devoted to public health. Among the current challenges
      which the Direction generale de la sante must meet are various types of potential
      health crisis, preparing the country for major health threats, reinforcing
      disease prevention and risk management, coordinating health institutions at the
      national level, and promoting French health policies within Europe and
      internationally.

PMID- 17450672
TI  - [The French National Public Health School 1962-1966].
AB  - The creation of the French National School of Public Health in 1960 was a major
      step forward in the field of Public Health, a concept which emerged at the end of
      the 19th century. Villerme, Louis and Parisot were its main proponents in France.
      From 1962 to 1966, the school opened in temporary buildings in Rennes (Brittany),
      before moving to its permanent premises in 1966. During its first four years the
      school provided eight basic courses, to which two new ones were subsequently
      added, one for hospital managers and one for health engineers. A large number
      offoreign students attended these courses, and two international seminars were
      organized on behalf of WHO.

PMID- 17450673
TI  - [Build the EHESP].
AB  - The legislator wished the creation of an important establishment named " School
      of High Studies in Public health " to give a greater efficiency and a better
      visibility to public health education. The implementation of this will raises the
      question of the structuring of the vocational and academic trainings in this
      particular field.

PMID- 17450674
TI  - [Public health education in France: challenges and future perspectives].
AB  - Public health difers from other fields of health education by its vast scope and
      by the diversity of its target populations. University training in public health
      is currently ensured in France by more than 300 permanent lecturers with
      significant research activity. Graduates find employment in hospitals and other
      public institutions. Public-sector managerial staff are educated by the National
      School of Public health. Currently, university training is poorly organized and
      coordinated in France. The creation of the Ecole des Hautes Etudes en Santo
      Publique provides an opportunity to reorganize the training infrastructure and
      calls for a reassessment of the place of universities in public health education.

PMID- 17450675
TI  - [Chondrocyte glycosyltransferases: new pharmacological targets for degenerative
      diseases of articular cartilage?].
AB  - Arthritis, osteoarthritis and other degenerative diseases characterized by
      cartilage deterioration are the most prevalent chronic human health disorders.
      Despite their major socioeconomic impact there is still no satisfactory
      treatment. Their frequency is increasing with the lengthening of life expectancy,
      creating a major public health challenge for coming years. It is important to
      diagnose such diseases at an early stage and to develop new effective therapies.
      We are attempting to develop new therapeutic approaches in this context, keeping
      in mind that cartilage is one of the few human tissues which is unable to
      regenerate. We intend to identify and characterize key proteins involved in the
      biosynthesis of cartilage matrix components. One innovative strategy consists of
      gene transfer, triggering overexpression of native or recombinant factors that
      can stimulate chondrocyte anabolic activity in order to promote cartilage repair
      The loss of matrix components, and especially glycosaminoglycans (GAG), is the
      earliest event in cartilage degeneration. We therefore looked at
      glycosyltransferases, and especially galactose beta1,3-glucuronosyltransferase-I
      (GlcAT-1), which catalyses one of the first steps in GAG biosynthesis. We found
      that any variation in GlcAT-I activity in chondrocytes or cartilage explants
      (overexpression, or repression with antisense RNA) affected the GAG content of
      cartilage. Interestingly, overexpression of this enzyme completely counteracted
      the GAG depletion produced by the proinflammatory cytokine interleukin 1-beta.
      The neosynthesized GAG was qualitatively identical to that present in the
      original cartilage matrix. These results are encouraging for therapeutic
      approaches based on gene transfer We also investigated the structure-function
      relationship of human recombinant GlcAT-I upon expression in the methyltrophic
      yeast Pichia pastoris. This allowed us to determine the molecular basis of the
      recognition of the donor and acceptor substrates of the enzyme. This
      multidisciplinary research, based on genetic and protein engineering, molecular
      modelling and glycochemistry will lay the groundwork for designing original
      glycomimetics able to stimulate GAG synthesis.

PMID- 17450676
TI  - [Biomaterials and cell therapy in cartilage disorders].
AB  - Joint cartilage has a poor intrinsic ability to heal. Common surgical treatments
      for traumatic lesions, after debridement of the chondral defect, include
      stimulation of subchondral bone (microfracture), perichondrial or periosteal
      grafting, and mosaicplasty (osteochondral cylinder transplantation). Autologous
      chondrocyte transplantation (ACT) was the first application of cell therapy to
      orthopaedic surgery. Despite promising results, several groups have tested tissue
      engineering protocols based on ex vivo colonization of biodegradable polymer
      matrices that are subsequently transplanted to the target site. Tissue
      engineering as a treatment for osteoarthritis is even more challenging.
      Transplantation of genetically modified cells is an interesting concept, based on
      the production of therapeutic proteins directly at the target site.

PMID- 17450677
TI  - [Targeted anti-cytokine therapies for osteoarthritis].
AB  - Proinflammatory cytokines such as interleukin-1 beta and, to a lesser extent,
      tumor necrosis factor (TNF) alpha, play a key role in the destruction of the
      cartilage matrix in osteoarthritis. Intraarticular injection of specific IL-I
      inhibitors or antagonists has been shown to slow disease progression in animal
      models of osteoarthritis. A first randomized placebo-controlled trial of a IL-1
      beta antagonist (a single intraarticular injection of 50 or 150 mg) had no
      analgesic effect during 3 months of follow-up. However, 150 mg of IL-1 ra had an
      early analgesic effect. Anti-TNF alpha therapy has also been tested in isolated
      cases of digital and knee osteoarthritis. Cytokine targeting in osteoarthritis is
      thus an appealing approach but one that needs to be validated in terms of the
      risk-benefit ratio.

PMID- 17450678
TI  - [Leptin: a link between obesity and osteoarthritis?].
AB  - In addition to aging, obesity is one of the most common underlying causes of
      osteoarthritis (OA). Mechanical loading, together with biochemical and systemic
      factors linked to altered lipid metabolism, are thought to contribute to the
      onset of OA. It has been suggested that OA is a systemic metabolic disease
      associated with lipid disorders affecting joint homeostasis. These gradual
      changes may be due to the local effect of adipokines, and especially leptin.
      Indeed, their relative levels in joints differ from that found in plasma. In
      particular, leptin levels are increased and adiponectin and resistin levels are
      reduced This hypothesis is supported by--leptin overexpression in OA cartilage
      and its correlation with the degree of cartilage destruction,--abundant leptin
      synthesis by osteophytes, and--the high leptin levels found in OA joints from
      female patients. This link between OA and adipokines provides new leads regarding
      the prevention of OA and the identification of new drug targets.

PMID- 17450679
TI  - [Articular reconstructions by a costochondral grafting (or osteochondral costal
      grafting)].
AB  - We describe a novel technique of costochondral autografting for the treatment of
      trapeziometacarpal arthritis, radioscaphoid osteoarthritis, malunion of the
      distal end of the radius, and osteoarticular loss of the MP joints of long
      fingers. The costal graft harvest technique is always the same. A 5-cm horizontal
      incision is made over the 9th rib, and the rib is exposed at the
      osteocartilaginous junction. Cartilaginous grafts are harvested with a scalpel,
      and osteocartilaginous grafts with a saw. Since 1992, 116 patients with trapezio
      metacarpal arthritis have been treated by partial trapeziectomy and autologous
      rib cartilage grafting. One hundred patients were reviewed with an average follow
      up of 5.6 years. The results were better than those of trapeziectomy with tendon
      interposition or ligamentous reconstruction, owing to good stability of the thumb
      ray height. For the treatment of radioscaphoid osteoarthritis following scaphoid
      non union or chronic scapholunate instability, partial carpal arthrodesis and
      resection of the first row are the classical techniques. As an alternative to
      these procedures, 18 patients were treated by resection of the proximal portion
      of the scaphoid and insertion of an osteochondral costal autograft. Mean follow
      up is 4.1 years. The results are excellent or good in 15 cases, fair in 2 cases,
      and poor in 1 case (luxation of the graft). Four patients with articular malunion
      of the distal radius received an osteocartilaginous costal graft to reconstruct
      the articular surface of the radius while avoiding partial or total arthrodesis
      of the wrist. Four patients with segmental osteoarticular loss of the longfingers
      were treated with the same technique, thereby avoiding silicone arthroplasty. We
      review the literature on cartilaginous rib grafts in maxillofajcial and
      orthopaedic surgery. In our experience, MRI and biopsy show viable cartilage but
      also histologic changes such as revascularization, fibrous transformation and
      bone metaplasia.

PMID- 17450680
TI  - [New developments in cartilage imaging].
AB  - Development of drugs able to modify the natural course of osteoarthritis is a
      major research objective. Imaging methods are needed to evaluate the effect of
      new medications in the experimental and clinical settings. Conventional
      radiographs are the gold-standard technique for routine imaging. However,
      magnetic resonance imaging (MRI) has transformed hyaline cartilage imaging by
      providing direct visualization without exposure to radiation. In addition, MRI
      can provide direct cartilage volumetry and tissue characterization for research
      purposes, using specific sequences. MRI can also give information on the content
      and organization of the collagen fibril network and proteoglycan chains, as well
      as water content. Computed tomography, arthrography and MR-arthrography require
      contrast medium injection into the joint space but provide high-resolution 3D
      images of the hyaline and fibrous cartilage.

PMID- 17450681
TI  - [The female urogenital system and high level sports].
AB  - High-level competition sports can have a variety of negative effects on the
      female urogenital apparatus. Perineal trauma is rare and is usually associated
      with certain sports (impalement or hydrotubation during water-skiing, indurated
      perineal nodules in racing cyclists, and horse-riders' perineum). Effort
      incontinence is seen in all sports involving abrupt repeated increases in intra
      abdominal pressure that may exceed perineal floor resistance. Sportswomen should
      be questioned about possible incontinence and be informed of preventive and
      therapeutic measures.

PMID- 17450682
TI  - [Analysis of a series of 100 mesenterico-portal vein resections during pancreatic
      resection].
AB  - Pancreatic resection is currently the only treatment offering the possibility of
      long-term survival for patients with pancreatic cancer. Mesentericoportal vein
      involvement used to be considered a contraindication to pancreatic resection, but
      recent advances in vascular surgery have gradually extended the indications of
      curative pancreatic resection to such cases. We report hereby our experience of
      100 pancreatic resections combined with mesentericoportal vein resection for
      pancreatic malignancies, performed between 1989 and 2005. This is one of the
      largest reported series. The overall mortality rate was 4% and the morbidity rate
      was 39%. Among the 76 patients who had pancreatic adenocarcinoma, the 5-year
      survival rate in case of limited mesenterico-portal vein wall involvement (up to
      the adventitia) was similar to that among patients without histological
      involvement of the portal vein wall (35.8% and 26.7%, respectively). These
      results support aggressive management consisting of resection and reconstruction
      of the mesentericoportal veins in patients with venous involvement, provided
      curative R0 resection is feasible.

PMID- 17450684
TI  - [Apropos of the proposal of the law relative to the possibility of removing
      anonymity of gamete donors].

PMID- 17450683
TI  - [Leukotrienes: potential therapeutic targets in cardiovascular diseases].
AB  - Leukotrienes are potent inflammatory mediators synthesized locally within the
      cardiovascular system through the 5-lipoxygenase pathway of arachidonic acid
      metabolism. The leukotrienes, consisting of dihydroxy leukotriene LTB4 and the
      cysteinyl leukotrienes LTC4, LTD4 and LTE4, act by targeting cell surface
      receptors expressed on inflammatory cells and on structural cells of vessel
      walls. LTB, induces leukocyte activation and chemotaxis via high- and low
      affinity receptor subtypes (BLT1 and BLT2), respectively. Recently, BLT,
      receptors were found on human vascular smooth muscle cells, inducing their
      migration and proliferation. Cysteinyl leukotrienes are vasoconstrictors and
      induce endothelium-dependent vascular responses through the CysLT, and CysLT2
      receptor subtypes. There is also pharmacological evidence for the existence of
      further CysLT receptor subtypes. Taken together, experimental and genetic studies
      suggest a major role of leukotrienes in atherosclerosis and in its ischemic
      complications such as acute coronary syndromes and stroke. Furthermore, the
      effects on vascular smooth muscle cells suggest a role in the vascular remodeling
      observed after coronary angioplasty, as well as in aortic aneurysm. Further
      experimental and clinical studies are needed to determine the potential of
      therapeutic strategies targeting the leukotriene pathway in cardiovascular
      disease.

PMID- 17450685
TI  - Recent consensus on the classification of rhinosinusitis--a way forward for
      research and practice?
AB  - Prior classification of rhinitis was into three categories: acute, subacute and
      chronic rhinosinusitis. The advantages of this classification were obvious but
      they were offset by some disadvantages. For example, the previous classification
      did not take account of the mechanisms underlying the condition or the clinical
      outcome. Hence, there was a need for evidence-based sinusitis classification
      guidelines. The American Academy of Otolaryngology-Head and Neck Surgery and
      other related societies published a classification of the condition and suggested
      clinical research strategies for patients with rhinosinusitis. The main
      conclusion was that sinusitis should be divided into four categories: acute
      (bacterial) rhinosinusitis, chronic rhinosinusitis (CRS) without polyps, CRS with
      polyps, and allergic fungal sinusitis. The aim of this current paper is to
      discuss the consensus for nomenclature, outline the proposed classification of
      different types of rhinosinusitis and to suggest some ways that we may audit
      these guidelines.

PMID- 17450686
TI  - Emergency surgical care in Scotland.
AB  - The introduction of waiting list initiatives and targets has resulted in the
      concentration of resources in politically important medical disciplines. This has
      inevitably meant that other medical disciplines, many of which involve emergency
      or unplanned admissions, have diminished resources. We believe that both the
      scale of this problem and the number of emergency or unplanned admissions to
      Scottish hospitals are underestimated. An analysis of the surgical mortality in
      Scotland between April 2004 and March 2005 was undertaken and the prevalence of
      emergency and unplanned admissions in the different surgical disciplines in
      different areas of Scotland was calculated. It is apparent that about 40% of all
      surgical admissions in Scotland are emergency or unplanned admissions with about
      70% being in general or orthopaedic surgery. About half of all admissions in
      neurosurgery, paediatric surgery, general surgery, orthopaedic surgery and
      cardiothoracic surgery are emergency or unplanned admissions. The numbers of
      emergency and unplanned admissions are much greater than is appreciated by many
      surgeons, managers and politicians. Recent changes in working hours, staffing
      levels and training have proved detrimental to the provision of good care for
      these patients. This situation is likely to worsen as the population ages and
      there are more emergency admissions. We believe that increasing centralisation is
      required in the major surgical disciplines if future problems are to be avoided.

PMID- 17450687
TI  - Trauma education of junior hospital doctors at a major Australian trauma service.
AB  - BACKGROUND: Junior hospital doctors are often involved in the early management of
      major trauma. The present study assesses the access to trauma education and
      clinical trauma exposure and skills of junior doctors at a major trauma service.
      METHODS: A semi-structured questionnaire was distributed to all resident medical
      officers (pre-registrar level) at a major trauma service. The questionnaire
      explored the quantity of exposure to major trauma, access to trauma education,
      self-perceived confidence and experience in basic trauma resuscitative procedures
      and future career aspirations. RESULTS: A 70% response rate was achieved; 11%
      were Basic Surgical Trainees. Mean length of time post-graduation was 2.5 years.
      Fourteen per cent of respondents had completed the Advanced Trauma Life Support
      (ATLS) course; another 14% were on the waiting list for the ATLS course. Sixty
      four per cent of respondents had attended fewer than five adult major trauma
      resuscitations in their entire career; 80% had never witnessed a major paediatric
      trauma resuscitation. Personal confidence in inserting a chest drain, management
      of cervical spine and airway was reported by 20%, 36% and 63% of respondents,
      respectively. The majority of respondents had never performed any of these
      procedures. Basic Surgical Trainees did not feel more confident in performing
      these procedures. Two-thirds (58%) of respondents nominated a future career
      aspiration which would potentially require involvement in the early management of
      major trauma. CONCLUSIONS: Despite working in a major trauma service, the studied
      cohort of resident medical officers, including Basic Surgical Trainees, have
      minimal exposure to major trauma, restricted access to trauma education and
      limited self-perceived confidence and experience in basic trauma resuscitative
      procedures.

PMID- 17450688
TI  - The European Working Time Directive and training in cardiothoracic surgery in the
      United Kingdom.
AB  - The European Working Time Directive (EWTD) limited average working hours for
      junior doctors to 58 per week in 2004. The Cardiothoracic Specialty Advisory
      Board conducted postal and email surveys of cardiothoracic trainees' work
      patterns and attitudes in 2003 and 2005-6. The results reveal an increase in
      shift-based working from 15% to 58% of respondents. One hundred per cent of
      respondents felt that the EWTD had had a negative impact on training, and only
      30% were satisfied with their training to date. Satisfied trainees were more
      likely to work in larger units as assessed by ITU beds (20.6 vs. 8.9, p < 0.001)
      and cardiac cases/year (1586.2 vs. 828.4, p < 0.001). They had performed more
      cardiac cases than their peers (72.7 vs. 26.7, p = 0.005). Fifty-two per cent
      thought that their quality of life improved after EWTD implementation. The EWTD
      is unpopular amongst cardiothoracic trainees, who perceive it as harming
      training. Overall trainee satisfaction is low. Larger units and increased
      personal operative experience are associated with trainee satisfaction. Training
      programmes must act vigorously to safeguard training quality before
      implementation of the 48-hour limit in 2009.

PMID- 17450689
TI  - Teaching surgeons about non-technical skills.
AB  - BACKGROUND: Analyses of adverse events in surgery reveal that underlying causes
      are often behavioural, such as communication failures, rather than technical. Non
      technical (i.e. cognitive and interpersonal) skills, whilst recognised, are not
      explicitly addressed in surgical training. However, surgeons need to demonstrate
      high levels of these skills, as well as technical proficiency, to maximise safety
      and quality in the operating theatre. This article describes a prototype training
      course to raise surgeons' awareness of non-technical skills. METHODS: The course
      syllabus was based on a new taxonomy of surgeons' non-technical skills (NOTSS)
      which has four principal categories: situation awareness, decision-making,
      communication and teamwork, and leadership. Three, one-day training courses were
      attended by 21 surgeons. RESULTS: All surgeons reported that they found explicit
      review and discussion of these skills and component behaviours helpful for self
      reflection. They rated the content as interesting and relevant and the majority
      declared their intention to make some changes to their behaviour during surgery.
      CONCLUSIONS: It was concluded that this type of training could enhance the
      surgical training portfolio and should be an integral feature of the development
      and assessment of operative skills.

PMID- 17450690
TI  - Postgraduate training options in dentistry--the RCSI roadmap.
AB  - This paper presents the RCSI roadmap for postgraduate training in dentistry. The
      importance of an approved training element is stressed in all aspects of this
      pathway to ensure that the trainee is provided with the best teaching and will
      emerge with the highest standards. It is critical in today's world that all
      healthcare professionals enter into lifelong learning in order to maintain the
      best level of care for our patients.

PMID- 17450691
TI  - Treatment of asymptomatic inguinal hernias.
AB  - Inguinal hernia repair is one of the most common operations in general surgery
      with rates of repair ranging from 10 per 10,000 population in the United Kingdom
      to 28 per 10,000 in the United States. Most inguinal hernias cause mild to
      moderate discomfort, which increases with activity. Up to one-third of the
      patients with an inguinal hernia scheduled for surgery have an asymptomatic
      swelling. Inguinal hernias are a significant socioeconomic burden with direct
      costs to the health service and indirect costs to the economy due to time off
      work following operation. In addition, the morbidity associated with the
      operation is often underestimated. Therefore, it is important to critically
      review the risks and complications related to inguinal hernia repair in those
      with minimal symptoms to formulate the best management strategy for these
      patients.

PMID- 17450692
TI  - Adjuvant systemic therapy for operable breast cancer.
AB  - Breast cancer is the leading cause of cancer death in women in England and Wales.
      Systemic adjuvant therapy for breast cancer reduces recurrence and mortality both
      in early and advanced breast cancer. This review primarily looks at the role of
      adjuvant systemic therapy following surgery. Chemotherapy and hormonal therapy
      has changed dramatically in the last few decades with the advent of newer
      aromatase inhibitors and newer chemotherapy drugs like taxol. Monoclonal
      antibodies targeted against breast cancer cells like trastuzumab are gaining
      ground recently in the adjuvant settings. In this article we have reviewed the
      recent evidences for the appropriate adjuvant therapy in operable breast cancer.

PMID- 17450693
TI  - Worthing nipple discharge aspirator.
AB  - Assessment of patients with nipple discharge traditionally involves using a
      custom made device or by massaging or squeezing the nipple-areola complex to
      elicit the discharge. This can be painful and embarrassing for the patient. We
      describe a nipple discharge aspirator that is effective, cheap, easily available,
      acceptable to the patient and avoids squeeze technique.

PMID- 17450694
TI  - Unusual hindgut malrotation and associated mesenteric vascular abnormality
      presenting as large bowel obstruction in an adult.
AB  - We report an unusual and not previously described congenital hindgut malrotation
      presenting as large bowel obstruction in an adult.

PMID- 17450695
TI  - Synchronous appendiceal tumours.
AB  - Primary appendiceal neoplasms are a rare clinical and pathological entity. We
      report a case of synchronous appendiceal tumours of different histological types
      which presented as a symptomatic palpable and radiologically apparent mass in the
      right iliac fossa. This case demonstrates the importance of pre-operative
      diagnosis of these neoplasms, as it may alter the surgical approach and obviate
      the need for additional surgery. Furthermore, some of the controversies
      associated with the management of an appendix mass in the elderly population are
      discussed.

PMID- 17450696
TI  - Preventing violence--caring for victims.
AB  - Part of the great tradition of surgery, exemplified by the Royal College precept,
      'From Here Health', is that surgeons are committed to prevention as well as cure.
      King James IV and his able contemporary in China, where this lecture was
      delivered, Emperor Hongzhi, would have approved of it. This tradition has,
      perhaps, been neglected since the emergence of public health as a medical
      specialty. However, opportunities and reasons for surgeons to contribute to
      prevention have never been greater. Community violence prevention--increasing
      public safety in the towns and cities in which surgeons work--is an example.
      Primary prevention of injury achieved by collecting and sharing unique
      information about weapons and the locations of assault, secondary prevention
      achieved by combining wound care with motivational interviewing to reduce alcohol
      misuse, and tertiary prevention achieved by early referral to mental health
      professionals for treatment of post-traumatic stress, have been integrated into a
      new care pathway which combines prevention with surgical care. Individuals and
      communities would benefit substantially if every surgical specialty incorporated
      prevention--a professionally highly-rewarding activity--into its training
      curriculum.

PMID- 17450697
TI  - Re: Post caesarean incisional hernia or scar endometrioma? Rao et al. Surgeon
      2006: 1; 55-56.

PMID- 17450698
TI  - Re: Golash V. Laparoscopic geometrical repair of ventral hernia. Surgeon 2006; 1:
      33-8.

PMID- 17450699
TI  - The use of the Limberg flap for reconstruction of pilonidal sinus excision
      wounds.

PMID- 17450700
TI  - Canadian Nursing Scholarship: a time to celebrate, a time to stand guard.

PMID- 17450701
TI  - Health information technology and nursing care.

PMID- 17450702
TI  - Nursing informatics: developing knowledge for nursing practice.

PMID- 17450703
TI  - Effectiveness of video-telephone nursing care for the homebound elderly.
AB  - This study had a dual purpose: to develop measures of change in functioning among
      the elderly, and to identify the characteristics of groups of homebound elderly
      whose functioning is significantly improved with video-telephone nursing care. As
      part of the evaluation of a home telecare program in Belgium, data from all 71
      elders who received home telecare were examined in order to describe the nature
      of the relationship between the care/support received and health outcomes. The
      elders' functioning was measured using 8 assessment scales. Eleven measures of
      change in functioning were developed using multi-dimensional scaling algorithms.
      Use of these measures in the decision tree model made possible the identification
      of groups of homebound elderly who showed significant improvement following tele
      nursing care in well-defined domains of functioning. The findings suggest that
      telecare is an alternative care model that could be integrated into existing home
      care services to provide older people with integrated health services.

PMID- 17450704
TI  - Women's responses to information on mammographic breast density.
AB  - The objective of this study was to determine the negative and positive outcomes
      of providing mammographic breast density (MBD) information to participants of a
      screening program. A randomized experiment was conducted with a sample of 618
      women 50 years or older with MBD greater than 50% of breast volume. The
      intervention consisted of reporting the presence of MBD in the screening
      mammography results letter that was sent along with an information pamphlet.
      Compared to the controls, more women in the intervention group described the term
      breast density correctly and recognized it as a risk factor for breast cancer.
      Although at the 4-week follow-up the intervention group indicated that they were
      "very likely" to have an annual clinical breast examination more frequently than
      controls, no differences were detected at 6 months. There were no significant
      differences on other behavioural or psychological measures, although at the 4
      week follow-up the control group perceived their risk for breast cancer, relative
      to other women their age, as "a lot lower" than did women in the intervention
      group. The results demonstrate a feasible and non-threatening way to provide
      women with important personalized information about breast cancer risk.

PMID- 17450705
TI  - Representing nursing practice: evaluating the effectiveness of a nursing
      classification system.
AB  - The purpose of this study was to examine the effectiveness of the International
      Classification for Nursing Practice (ICNP) in representing the contributions of
      nursing to health-care outcomes in Canada. The ICNP BetaVersion was used to code
      retrospective nursing data extracted from patient records originating in acute
      care, in-patient mental health care, home care, and long-term-care practice
      settings. In spite of wide variation in documentation practices, ICNP achieved
      matches with the majority of nursing data. The study revealed areas for
      improvement in the ICNP BetaVersion, specifically with regard to granularity
      related to the use of natural language terms and professional terms.
      Recommendations for further development through research in nursing-sensitive
      outcomes are discussed.

PMID- 17450706
TI  - Effectiveness of computer-based tailoring versus targeting to promote use of
      hearing protection.
AB  - The purpose of this study was to evaluate the effectiveness of 2 computer-based
      interventions and booster messages on construction workers' use of hearing
      protection. Construction workers (n = 343) were randomly assigned to receive
      tailored (addressing individual characteristics) or targeted (addressing shared
      characteristics) education, with or without booster messages, in an experimental
      4-group pretest-post-test design. Post hoc message matching compared the value of
      tailored and targeted approaches. Participants improved use of hearing protection
      from 42% to 50% of the time they were exposed to noise 1 year post-intervention.
      Differences between intervention groups were not significant. The significant
      improvement in use of hearing protection demonstrates that interventions can have
      an impact on preventing noise-induced hearing loss. Since targeted and tailored
      intervention groups did not significantly differ in use of hearing protection,
      and since targeted interventions are less costly to develop, targeted
      interventions offer greater value.

PMID- 17450707
TI  - Exploring women's psychoneuroendocrine responses to cancer threat: insights from
      a computer-based guided imagery task.
AB  - It is proposed that computers could be used to examine patients' subjective
      experience in the face of cancer threat. This study provides initial validation
      of a computer-based stress task by examining the psychological, autonomic, and
      endocrine aspects of an individual's subjective experience of cancer threat
      surrounding mammography screening. A repeated measures design was used. A total
      of 38 healthy women performed a stress task (pertaining to mammography) and a
      control task (pertaining to osteoporosis prevention) on separate days during
      which psychological, autonomic, and endocrine reactions were monitored. Compared
      with the control task, the stress task induced higher autonomic responses (skin
      conductance and heart rate variability) and endocrine responses (salivary
      cortisol) but not psychological distress. Further, both the autonomic (skin
      conductance) and endocrine responses to cancer threat were moderated by mastery,
      a trait known to have a stress-buffering effect. Yet such a moderating effect was
      not observed for psychological indices of stress--that is, mood. Implications for
      nursing research and interventions are discussed.

PMID- 17450708
TI  - Methodological considerations in evaluating eHealth interventions.
AB  - Advances in information and communication technologies shape consumers' attitudes
      towards engagement in their own health and their interface with the health-care
      system. The use of eHealth tools holds promise for supporting and enabling health
      behaviour change and the prevention and management of chronic diseases. The
      authors review issues related to study design, treatment implementation, and
      outcome measurement in eHealth trials, providing examples from the literature and
      from their own ongoing studies. Selection of a comparison group and design
      considerations related to participant preferences are based on the state of the
      science and current practice in the particular field. Randomized designs allow
      for control of selection bias and are favoured in both efficacy and effectiveness
      trials of eHealth interventions. Depending on the choice of comparison groups,
      eHealth applications must be fairly robust to demonstrate their efficacy above
      and beyond active controls. Strategies to ensure treatment fidelity and ongoing
      participant engagement can be challenging and are not always successful. Patient
      reported outcomes are common to eHealth studies. Other outcomes, such as the
      costs associated with new eHealth applications, are equally if not more important
      for decision-makers. This discussion is intended to inform future trials and
      thereby serve to advance the science of eHealth.

PMID- 17450709
TI  - Using interactive health communication technology in a renewed approach to
      nursing.

PMID- 17450710
TI  - The efforts of critical care nurses to pass along knowledge about patients.
AB  - The purpose of this descriptive, interpretive study was to explore and describe
      the work of critical care nurses in sharing and discussing their knowledge about
      patients with other members of the health-care team. Three questions were
      examined: Which aspects of their understanding of patients do nurses pass along?
      How is knowledge passed along? To what ends is knowledge passed along? Data
      collection took place in 2 intensive care units in a tertiary care hospital and
      involved observation of 10 nurses followed by interviews. Nurses "filled out the
      picture" for others by passing along knowledge about the patient's status,
      patient responses over time, interventions that had been beneficial, and the
      patient as a person. This aspect of nurses' work was facilitated by proximity to
      both patients and other team members and the inclusion of nurses in
      multidisciplinary rounds. The results have implications for staffing patterns,
      the layout of hospital units, the structure of rounds, and nursing education.

PMID- 17450711
TI  - Giving voice to informal caregivers of older adults.
AB  - This study focused on the experiences of informal caregivers of older adults and
      explored whether employment, use of home-care services, or other factors
      influence the health of caregivers and their ability to manage their caregiving
      and other responsibilities. Focus groups conducted with 26 caregivers and
      personal interviews with 4 caregivers identified 12 themes under 5 conceptual
      areas: caregiver health, relationships, independence, employment, and use of home
      care services. The findings reveal that caregiving coupled with other
      responsibilities can have serious health effects. Participants spoke of the
      tenuous balance of decision-making control between caregiver and care recipient.
      Many caregivers expressed a desire to be included as part of the formal health
      care team. Implications for nursing are discussed.

PMID- 17450712
TI  - "Inside and outside": Sikh women's perspectives on cervical cancer screening.
AB  - Cervical cancer can be detected at an early stage through regular screening. The
      literature suggests that cervical cancer in immigrant women, a growing population
      in Canada, is less likely to be detected early than it is in the general
      population, as immigrant women tend not to take advantage of screening.
      Culturally appropriate screening services for immigrant women are few. A
      qualitative descriptive study was conducted with female members of an urban Sikh
      community in Canada to explore perspectives on cervical cancer screening. In
      depth interviews (13) and focus groups (3) were carried out to uncover challenges
      to cervical cancer screening. The researchers identified a prevailing theme of
      "inside/outside" whereby the women felt confined to their community, finding it
      difficult to move "outside" into Canadian society in order to participate in
      screening. Lack of knowledge about the importance of prevention, influence of
      family and community, and health-provider issues affected the women's access to
      screening. The results will be helpful for nurses planning and delivering
      screening services to Sikh women.

PMID- 17450713
TI  - Dr John McLean OBE: his life and times.

PMID- 17450714
TI  - Stories from the BDA museum collections.

PMID- 17450715
TI  - The day a president disappeared.

PMID- 17450716
TI  - Professor Gerald Bernard Winter MB BS, DCH, FDSRCS ENG, FFD RCSI, FRCPCH (1928 -
      2002).

PMID- 17450717
TI  - Jewish dentists under Hitler.

PMID- 17450718
TI  - Gustav Ginsberg: a dental tale (1872-1922).

PMID- 17450719
TI  - References to the palate in the Old Testament.

PMID- 17450720
TI  - [Dynamics of litter decomposition and phosphorus and potassium release in
      Jinggang Mountain region of Jiangxi Province, China].
AB  - By using litter bag method, a 2-year experiment was made to study the dynamics of
      litter decomposition and phosphorous and potassium release of Castanopsis eyrei
      dominated evergreen broad-leaved forest (EBF), Pinus taiwanensis, Cyclobalanopsis
      nubium and Castanopsisfabri coniferous and broad-leaved mixed forest (CBF) , and
      Rhododendron simiarum-dominated mountainous dwarf forest (MDF) in Jinggang
      Mountain region of Jiangxi Province, China. In each forest, litter bags were
      placed on soil surface (aboveground treatment, AG) and at the depth of 10 cm
      (below-ground treatment, BG). An inverse exponential relationship was found
      between litter decay rate and time for each of the three forests. The average
      value of the litter mass loss of AG and BG was 50.6% for EBF, 41. 7% for CBF, and
      40. 13% for MDF by the end of first year, and 60.95% for EBF, 57. 06% for CBF,
      and 56. 60% for MDF by the end of second year, indicating that the litter
      decomposition of the forests was faster in first year than in second year. The
      annual litter loss decreased in the order of EBF > CBF > MDF, and that of AG was
      significantly higher than that of BG in first year but no significant difference
      was found in second year. According to the model simulation by Olson' s
      exponential function, it might take 6. 8-9. 9 years to reach 95% of decay (t095)
      for the forests investigated, compared with 8-17 years for warm temperate forests
      and 2 -8 years for south subtropical forests. The t0.95 value of the three test
      forests increased in the order of EBF < CBF < MDF. A net phospbhorus (P)
      immobilization was observed in the process of litter decomposition, with the
      intensity decreased in the order of MDF > CBF > EBF, which was related to the
      initial P content and C/P ratio of the litter. As for potassium ( K) , it was net
      release in most cases. By the end of the experiment, the release rate of P had
      little difference between AG and BG, while that of K was significantly higher in
      AG than in BG.

PMID- 17450721
TI  - [Dynamics of soil water under Vernicia fordii plantation in hilly red soil region
      of Southern China].
AB  - By using time domain reflectometry (TDR) , a fixed-position monitoring was made
      on the dynamic characteristics of soil water under Vernicia fordii plantation in
      the hilly red soil region of Southern China. The results showed that there was a
      significant difference in the soil water storage among different months, and the
      dynamics of soil water could be described as the phases of accumulation,
      depletion, and stabilization. Soil water had a significant variation in its
      vertical distribution, and the variation pattern differed in different seasons.
      Significant correlations existed between soil water storage and meteorological
      factors such as relative humidity (RH) , air temperature (t) , vapor pressure
      deficit (VPD) and rainfall (R) (P < 0. 05). After rain, soil water loss had a
      significant hyperbolic correlation with drought duration, while soil water
      storage had a significant linear negative correlation with this duration (P < 0.
      05). With the extension of drought duration after rain, soil water loss tended to
      vary gently with increasing soil depth.

PMID- 17450722
TI  - [ISSR analysis on genetic diversity of endangered relic shrub Sinocalycanthus
      chinensis].
AB  - By using inter-simple sequence repeat (ISSR) markers technique, this paper
      studied the genetic diversity of ten populations of endangered relic shrub
      Sinocalycanthus chinensis. The results showed that at species level, the
      percentage of polymorphic loci (P) was 73. 08% , Shannon' s index (h) was 0.
      3097, and Nei' s gene diversity (I) was 0. 1987, indicating a high level of
      genetic diversity, but at population level, they were 23. 65% , 0. 1251 and 0.
      0839, respectively, suggesting a low level of genetic diversity. The analysis of
      molecular variance (AMOVA) demonstrated that there was a relatively high level
      (57. 11% ) genetic variation among the populations, with the gene differentiation
      coefficient ( Gst ) and gene flow being 0. 5779 and 0. 3651, respectively. The
      high genetic differentiation among populations and the low genetic diversity
      within populations could be attributed to the habitat fragmentation and the
      limited gene flow among populations. Through cluster analysis, the ten
      populations of S. chinensis were classified into two groups, with the eight
      populations in Lin' an City forming a group and other two in Tiantai County
      forming another group.

PMID- 17450723
TI  - [Age structure and growth characteristic of Castanopsis fargesii population].
AB  - In this paper, the age structure and growth characteristics of Castanopsis
      fargesii population in a shade-tolerant broadleaved evergreen forest were
      studied, aimed to understand more about the regeneration patterns and dynamics of
      this population. The results showed that the age structure of C. fargesii
      population was of sporadic type, with two death peaks of a 30-year gap. This
      population had a good plasticity in growth to light condition. Because there were
      no significant differences in light condition under the canopy in vertical, the
      saplings came into their first suppression period when they were 5-8 years old,
      with a height growth rate less than 0. 1 m x a(-1) lasting for 10 years. The
      beginning time of the first growth suppression period was by the end of the first
      death peak of the population, and the ending time of the first growth suppression
      period was at the beginning of the second death peak of the population,
      demonstrating that growth characteristic was the key factor affecting the age
      structure of C. fargesii.

PMID- 17450724
TI  - [Indirect effects of precipitation on litter decomposition of Quercus mongolica].
AB  - The effect of precipitation variation on chemistry of Quercus mongolica leaf
      litters was examined by analyzing litters of Mongolia oak saplings under 4
      precipitation gradients, and the decomposing process of these leaf litters in Q.
      mongolica dominated forest was assessed using litter bag method. The results
      showed that under less precipitation, the litter had a higher decomposition rate,
      and its N, P and K mineralized quickly. The initial concentrations of N, P, and K
      increased, while that of lignin decreased significantly. With increasing
      precipitation, the mineralization rates of N, P and K in litter decreased. Its
      initial N concentration decreased, while the relative content of lignin
      increased. The mass loss patterns of four type litters fitted exponential model,
      and the decomposition rate could be well predicted by their lignin/N ratio. The
      decomposition rate of the litters with higher lignin and lower N was best related
      to their N concentration, while that of the litters with lower lignin and higher
      N was strongly correlated with their lignin concentration. It was proved that
      precipitation had a significant effect on the litter substrate quality of Q.
      mongolica, and thus, changed the decomposition process of the litter indirectly.

PMID- 17450725
TI  - [Optimal disposition of water conservation forests in watershed].
AB  - Based on the measurements of canopy interception, litter water-holding capacity
      and soil water storage of different stands in the Erdaoqiao watershed of upper
      Nenjiang River, the optimal disposition of water conservation forests in this
      watershed was approached by the method of analytical hierarchy process (AHP). The
      results showed that in this watershed, the optimal vegetation structure should be
      24. 86% of natural birch forest, 16. 30% of natural Dahurian birch forest, 44.
      49% of natural broadleaved mixed forest, 10. 88% of larch plantation, and 3. 47%
      of grassland. After optimization, the water conservation capacity of the
      watershed could be improved obviously, with soil available and maximum moisture
      contents increased by 33. 05% and 27. 78% , re-

PMID- 17450726
TI  - [Soil hydro-physical properties under broadleaved Korean pine and dark coniferous
      forests on northern slope of Changbai Mountains].
AB  - The measurement of soil hydro-physical properties under broadleaved Korean pine
      and dark coniferous forests on the northern slope of Changbai Mountains showed
      that under these two forest types, soil bulk density and porosity had the same
      variation trend with increasing soil depth, i. e. , bulk density and capillary
      porosity increased, while total porosity and non-capillary porosity decreased.
      The average bulk density, total porosity, capillary porosity and non-capillary
      porosity in 0-100 cm soil layer were 1. 41 g x cm(-3), 52. 31% , 46. 11% and 6.
      20% under broadleaved Korean pine forest, and 0. 98 g x cm(-3) , 50. 65% , 40.
      32% , 10. 33% under dark coniferous forest, respectively. Owing to the
      differences in soil hydro-physical properties, the water storage capacity in 0
      100 cm soil layer was 619. 89 t x hm(-2) under broadleaved Korean pine forest,
      but 1 033.05 t X hm(-2) under dark coniferous forest. For these two forests,
      their soil water characteristic curves were consistent with the general one.

PMID- 17450727
TI  - [Microelement contents of litter, soil fauna and soil in Pinus koraiensis and
      broad-leaved mixed forest].
AB  - The analysis on the Mn, Zn and Cu contents of litter, soil fauna and soil in
      Pinus korazenszis and broad-leaved mixed forest in Liangshui Natural Reserve of
      Xiaoxing' an Mountains showed that the test microelement contents in the litter,
      soil fauna and soil all followed the sequence of Mn > Zn > Cu, but varied with
      these environmental components, being in the sequence of soil > litter > soil
      fauna for Mn, soil fauna > litter and soil for Zn, and soil fauna > soil > litter
      for Cu. The change range of test microelement contents in litter was larger in
      broad-leaved forest than in coniferous forest. Different soil fauna differed in
      their microelement-enrichment capability, e. g. , earthworm, centipede, diplopod
      had the highest content of Mn, Zn and Cu, respectively. The contents of test
      microelements in soil fauna had significant correlations with their environmental
      background values, litter decomposition rate, food habit of soil fauna, and its
      absorbing selectivity and enrichment to microelements. The microelements
      contained in 5-20 cm soil layer were more than those in 0-5 cm soil layer, and
      their dynamics differed in various soil layers.

PMID- 17450728
TI  - [Species diversity of Brasenia schreberi community in different habitats].
AB  - By using Braun-Blanquet Cover Abundance Scale method, the species diversity of
      Brasenia schreberi community in Dongshan Town (Suzhou City, Jiangsu Province) and
      Zhuantang Town (Hangzhou City, Zhejiang Province) was studied, and the results
      showed that in these two towns, B. schreberi community was of simple species
      composition and relatively low species diversity. The Shannon-Wiener diversity
      index, Simpson ecological dominance index, and community evenness index all
      increased obviously when the habitat shifted from pond center to bank nearby. B.
      schreberi community was similar in the same type habitats of these two towns, and
      of much more similarity in pond center than at bank nearby. Compared with
      Zhuantang Town, Dongshan Town had a greater difference of B. schreberi community
      between the two habitats.

PMID- 17450729
TI  - [Regional evapotranspiration of different land covers based on remote sensing].
AB  - In this paper, surface energy balance system (SEBS) was extended into a regional
      daily evapotranspiration (ET) estimation model based on remote sensing data, and
      the extended SEBS was applied to estimate the regional daily ET of Huanghe-Huaihe
      Haihe rivers region in Northern China Plain by using MODIS/TERRA data. An
      analysis was made on the estimated daily ET characteristics of different land
      covers in the study area by using the spatial analysis module of ArcGIS. Since
      there were no field observations of ET on each land cover, the estimated daily ET
      of different land covers was compared with each other, taking the data on April
      17, 2001 as an example. The results showed that the regional daily ET estimated
      by SEBS was reasonable. Wetland and cultivated land had the highest daily ET
      value, followed by forest-, bush- and grassland, and waste land. The
      characteristics of the daily ET over these land covers were accorded with the
      existing knowledge of ET over this region, and coincident to the results of
      previous work in this area. It was interesting that the residential area also had
      a higher ET value, which was explained as the higher ET of the land use types, e.
      g. , water body, street trees, and grass parcels in the resident areas within the
      pixel scale. The spatial inhomogeneity of ET among the forest-, bush-, grass- and
      cultivated land covers were caused by the spatial inhomogeneous soil water
      content under these land covers, and the spatial inhomogeneity of ET over
      cultivated land could be a potential indicator of making reasonable and effective
      irrigation schedule for the farmland. The limitations of using SEBS model in
      daily ET estimation were discussed, especially the possibility of underestimating
      the ET over water body and wetland covers due to the unsuitable surface
      parameterization scheme for these land types in the model.

PMID- 17450730
TI  - [Time series analysis of soil water on sloping land in red soil hilly region].
AB  - Based on time series analysis, the correlation between soil water and
      precipitation on the sloping land in red soil hilly region under two land use
      modes was studied from March to September, 2002-2004. The results showed that
      precipitation was not an autocorrelation series, while soil water at the depths
      of 10, 30, 50, 70 and 90 cm was an autocorrelation series with 30-45 days of time
      correlation range. Precipitation and land use mode were the main factors
      affecting the correlation of soil water and precipitation. The effect of
      precipitation weakened gradually with increasing soil depth. This effect lasted 7
      8 days in upper soil layers (0-10 and 0-30 cm) , but no marked regularity was
      observed in deeper soil layers. 2-3 days after raining, precipitation had the
      most prominent effect on soil water in 0-100 cm soil layer. The correlation time
      range was 1-3 days shorter in dry season than in wet season. When it didn' t rain
      more than 5 days, the water content in topsoil would decrease, and even, lead to
      seasonal drought. Compared with farmland, tea plantation had a weaker correlation
      between soil water and precipitation in surface soil, but a stronger and more
      persistent correlation in soil layers below 50 cm.

PMID- 17450731
TI  - [Effects of land use and management practice on farmland soil quality in Yanhuai
      basin of Beijing].
AB  - In April 2005, a total of 41 soil samples were collected from the sandy loam soil
      (Ustochrepts) under orchard, vegetable, corn (Zea maize L. ) and soybean (Glycine
      max L. ) in Yanhuai basin of Beijing, and their physical, chemical, and
      biological properties were analyzed. The results showed that the contents of soil
      organic carbon (SOC), total nitrogen (TN) and total phosphorus (TP) in vegetable
      field, orchard field, and high-input corn field were obviously higher than those
      in soybean field and mid- and low-input corn fields. In these fields, SOC content
      varied from 7. 67 to 10. 00 g x kg(-1), TN content varied from 0. 75 to 1. 12 g x
      kg(-1) , and TP content varied from 0. 63 to 1. 00 g x kg(-1). Soil available
      phosphorus (AP) content and electric conductance (EC) were significantly higher
      in vegetable field than in other fields, while no significant differences in soil
      physical properties were observed among the four land use types. The soil quality
      index of orchard and vegetable fields was 0. 525 and 0. 503, respectively, being
      higher than those of corn and soybean fields (0. 417-0. 494). Vegetable field had
      the highest efficiency of soil nutrients, but non-point source pollution risk
      should be minded. For soybean field and mid- and low-input corn fields, intensive
      management should be practiced to improve their soil quality.

PMID- 17450732
TI  - [Arsenic accumulation in different agricultural soils in Shouguang of Shandong
      Province].
AB  - The study on the soil arsenic (As) accumulation under different types of
      agricultural use in Shouguang of Shandong Province showed that farmland soils had
      an average As content of 9. 63 mg x kg(-1) , with the highest being 15. 15 mg x
      kg(-1) . Compared with the local background value (9. 3 mg As x kg(-1)) , 53. 1%
      of soil samples was detected as As enrichment. The soil As content was high in
      the west, east and north parts of Shouguang, relatively lower in the middle part,
      and the lowest in the south part. Different agricultural use had an obvious
      effect on the soil As content, which was decreased in the order of wheat/maize
      land > cotton field > protected vegetable land > uncovered vegetable land. Such a
      difference in soil As content was mainly affected by agricultural activities.
      With the increasing year of vegetable planting, soil As content had an increasing
      trend, because the As input from pig dung and chicken feces was the main source
      of soil As in protected vegetable land. Soil As enrichment could be reduced to
      some degree by applying soybean cake fertiliz-

PMID- 17450733
TI  - [Calculation of crop evapotranspiration in greenhouse].
AB  - Based on Penman-Monteith equation, a simplified formula for calculating the crop
      evapotranspiration in greenhouse was deduced by introducing the parameter of crop
      canopy height and modifying the item of aerodynamics related to wind velocity.
      The deductive procedure was analyzed theoretically, and the formula was validated
      with meteorological data. The results showed that the modified Penman-Monteith
      equation had a higher precision of prediction, with a relative deviation of 4. 7%
      17. 1% and 11. 1% on average, being suitable to calculate the crop
      evapotranspiration in greenhouse.

PMID- 17450734
TI  - [A dynamic knowledge model for designing suitable scheme of rapeseed sowing and
      transplanting].
AB  - Based on the sum-up and abstraction of the relationships of rapeseed growth
      characters with ecological environment, cultivar type, production condition and
      yield target, a dynamic knowledge model was developed by using knowledge
      engineering and system modeling method, which could be used for designing a
      suitable sowing and transplanting scheme of different rapeseed varieties under
      different spatial and temporal environments. Case studies on the knowledge model
      with the data sets of three different sites, nine different variety types, and
      two different sowing styles indicated a good performance of the model system in
      decision-making, explanation, and wide applicability.

PMID- 17450735
TI  - [Effects of foliage spraying sodium bisulfite on photosynthetic physiological
      characteristics of Citrus sinensis with sulphur deficiency].
AB  - The study with solution culture showed that Citrus sinensis plants with sulphur
      deficiency and with sulphur deficiency plus foliage spraying sodium bisulfite (
      NaHSO3 ) halfway had notably decreased photosynthetic pigment content, soluble
      protein content, net photosynthetic rate (Pn), initial fluorescence (Fo) ,
      maximum fluorescence (Fm) , photochemical efficiency (Fv/Fm) and electron
      transmit rate (ETR) , compared with those having normal sulphur supply. After 35
      days of growth, their photosynthetic pigment content decreased by 23. 45% and 11.
      32% , and soluble protein content decreased by 43. 43% and 25. 30% ,
      respectively, while no significant differences were observed between the plants
      with sulphur deficiency plus foliage spraying NaHSO3 throughout the experiment
      and those having normal sulphur supply, suggesting that foliage spraying NaHSO3
      could be an effective way to supply sulphur element to the C. sinensis with
      sulphur deficiency, but hard to rectify sulphur deficiency symptom when the
      plants suffered from a severe sulphur deficiency stress for a long time.

PMID- 17450736
TI  - [Effects of drought and waterlogging on flag leaf post-anthesis photosynthetic
      characteristics and assimilates translocation in winter wheat under high
      temperature].
AB  - With winter wheat varieties Yangmai 9 and Yumai 34 as test materials, this paper
      studied post-anthesis photosynthetic characteristics in flag leaves, the
      translocation of assimilates and nitrogen stored in vegetative organs before and
      after anthesis and their relationships with grain yield and quality under
      different temperature and water conditions. The results showed that high
      temperature, drought, and waterlogging all had significant negative effects on
      photosynthetic rate and chlorophyll content (SPAD value) of flag leaves, and the
      effects of drought and waterlogging were greater under high temperature than
      under optimum temperature. The translocation amount and rate of assimilates and
      nitrogen stored in vegetative organs before anthesis declined in the order of
      drought > normal soil moisture content > waterlogging under optimum temperature,
      but normal soil moisture content > drought > waterlogging under high temperature.
      The amount of post-anthesis assimilates translocated into grain declined in the
      order of normal soil moisture content > waterlogging > drought under optimum
      temperature, but normal soil moisture content > drought > waterlogging under high
      temperature, while that of post-anthesis accumulated nitrogen declined in the
      order of normal soil moisture content > waterlogging > drought under both high
      and optimum temperature. The starch and protein contents in grains were the
      lowest under high temperature x waterlogging, but the highest under optimum
      temperature x normal soil moisture content. Overall, the decrease of grain mass
      and starch content under high temperature and water stresses was associated with
      the lower photosynthetic rate and less post-anthesis assimilates accumulation,
      while grain protein content was related to the translocation amount and rate of
      nitrogen stored before anthesis.

PMID- 17450737
TI  - [Effects of free-air CO2 enrichment (FACE) on dry matter production and
      allocation in wheat].
AB  - A free-air CO2 enrichment (FACE) experiment was conducted in 2001-2003 to study
      the effects of predicted higher CO2 levels on the dry matter (DM) production and
      allocation in winter wheat variety Ningmai 9. The results showed that under FACE,
      the DM production had an increase of 10. 8% , 31. 6% , 40. 5% and 27. 2% during
      the growth periods from sowing to wintering ( Period 1 ) , wintering to jointing
      ( Period 2) , jointing to booting ( Period 3) , and booting to heading (Period 4)
      , respectively, but a decrease of 5. 5% in the period from heading to grain
      maturity (Period 5). As a result, the final total biomass at maturity was
      increased by 13. 6%. FACE had no significant effect on leaf area index (LAI) and
      net assimilation rate (NAR) in Period 1, but made the LAI in Period 2 increased
      obviously, and the NAR decreased dramatically in Period 3. Under FACE, the
      proportion of leaf to total above-ground DM decreased, while that of stem
      (including sheath) to total above-ground DM showed an opposite trend in the whole
      growth period. The percentage and total amount of soluble sugar and starch in the
      stem at grain-filling stage were also increased obviously under FACE.

PMID- 17450738
TI  - [Effects of irrigation amount at seedling stage on physiological characteristics
      and yield of peanut].
AB  - Taking two peanut varieties with different drought-resistance Luhua 11 and Nongda
      818 as test crops, the effects of different irrigation amount at seedling stage
      on their physiological characteristics and yield were studied from 2003 to 2004.
      The results showed that with decreasing irrigation amount, the leaf
      photosynthesis rate of test varieties decreased, while malondialdeyde (MDA)
      content increased. Watering 60-80 mm ( suitable drought) enhanced the activities
      of superoxide dismutase (SOD) , peroxidase (POD) and catlase (CAT) , and
      increased the content of soluble protein. After re-watering by the end of
      treatments, the activities of SOD, POD and CAT and the contents of soluble
      protein and MDA decreased significantly, while photosynthesis rate increased
      obviously. The pod and kernel yield decreased with decreasing irrigation amount,
      and Luhua 11 had a greater loss than Nongda 818, indicating that Nongda 818 was
      more drought-tolerant than Luhua 11. It was suggested that under water-saving
      culture, the irrigation amount at seedling stage could not be less than 80 mm for
      Luhua 11, and less than 60 mm for Nongda 818.

PMID- 17450739
TI  - [Effects of weak light on photosynthetic characteristics and chloroplast
      ultrastructure of non-heading Chinese cabbage].
AB  - The study with two varieties of non-heading Chinese cabbage shade-tolerant
      'Aiwang' and shade-sensitive 'Luyou' showed that after shading, the total
      chlorophyll and chlorophyll b contents of 'Aiwang' went up greatly, but the net
      photosynthetic rate (Pn) , light compensation point (LCP), light saturation point
      (LSP), apparent quantum yield (AQY) and carboxylation efficiency (CE) of both
      'Aiwang' and 'Liiyou' all went down, and the decline of all test parameters
      except LCP was slighter for 'Aiwang' than for ' Luyou'. Under weak light
      condition, the PS II of 'Luyou' was injured, and as a result, the Fv/Fm, ETR, Phi
      PS II, and qp of 'Luyou' had a greater decline than those of 'Aiwang'. In the
      chioroplast of 'Ltiyou' , cracks and foveolae appeared, most of stroma lamellae
      fractured, grana lamellae disaggregated, and mitochondria were nearly empty with
      the decrease of contents. In contrast, the chioroplast structure of 'Aiwang' was
      flawless, and its mitochondria grew well. It was suggested that weak light could
      damage the photosynthetic organization of plant, but different varieties showed
      different responses.

PMID- 17450740
TI  - [Effects of rice seedlings horizontal distribution on the dynamics of rice
      population, canopy light transmittance rate and panicle characteristics].
AB  - The study with stronger tillering hybrid rice ' D-you 527' showed that the more
      the irregularity of the seedlings horizontal distribution, the more colony stem
      tillers the plants would have. Such a difference was significant 34 days after
      transplanting, but not significant at full heading stage. After transplanting,
      the trend that the variation coefficient increased with increasing irregularity
      of horizontal distribution presented gradually, and the difference became
      significant after jointing stage. Comparing with uniform distribution, an
      irregular horizontal distribution of the seedlings could benefit the canopy light
      transmittance rate and the panicle characteristics of rice.

PMID- 17450741
TI  - [Effects of boron on indole-3-acetic acid transportation in intact phaseolus
      aureus plant].
AB  - With intact Phaseolus aureus plant as test material, this paper studied the
      effects of boron deficiency on its axillary bud growth and polar auxin
      transportation. The results showed that boron deficiency induced axillary bud
      growth significantly, while applying indole-3-acetic acid (IAA) could suppress
      the axillary bud growth induced by the decapitation of boron sufficient plant.
      When the plant deficient in boron was decapitated, applying IAA could delay the
      axillary bud growth. Compared with boron sufficient plant, the plant deficient in
      boron had an inhibited auxin basipetal movement in terms of the shorter distance
      of 3H-IAA peak from apex, and less total radioactivity detected in stem. No
      radioactivity was found in the axillary buds in any of the treatments, suggesting
      that the basipetal IAA transportation in stem rather than the IAA accumulation in
      bud was required for the inhibition of bud growth. A 24 h boron supply to the
      boron deficient plant could restore its 3H-IAA transportation.

PMID- 17450742
TI  - [Effects of soil water content on H2O and CO2 exchange in tomato leaves in
      different seasons].
AB  - With tomato variety "L402" as test crop, this paper studied its photosynthetic
      and transpiration characteristics in different seasons under different soil water
      contents. Three treatments were installed, i. e. , 80% ( I ) , 65% ( II ) and 50%
      ( III ) soil water content. The results showed that when cultivated in spring,
      the photosynthetic rate (Pn) and transpiration rate (Tr) of tomato leaves were
      the highest in treatment I , followed by treatments II and Ill, while the water
      utilization efficiency ( WUE) was the highest in treatment II. The decrease of
      soil water content changed the diurnal variations of Pn and Tr significantly, and
      aggravated the midday depression of photosynthesis. The tomato growing in winter
      had the lowest Pn and Tr in treatment mI , while no difference was observed
      between treatments I and II. No midday depression of photosynthesis was found
      among the three treatments. The WUE was the highest in treatment m , and the
      lowest in treatment I . All of these suggested that the tomato plants cultivated
      in different seasons had different responses to soil water content. The diurnal
      variations of their Pn and Tr were significantly different, and the Pn and Tr of
      spring tomato were significantly higher than those of winter tomato under the
      same soil water content.

PMID- 17450743
TI  - [Effects of D-arginine on polyamine content and anaerobic respiration metabolism
      of cucumber seedling roots under hypoxia stress].
AB  - By the method of solution culture, this paper studied the effects of D-arginine
      on the seedling roots polyamine content and anaerobic respiration metabolism of
      two cucumber ( Cucumis Sativus L. ) cultivars Zhongnong No. 8 and Lubachun No. 4
      differed in hypoxia tolerance. The results showed that under hypoxia stress, the
      putrescine (Put), spermidine (Spd) and spermine (Spm) contents in the seedling
      roots of test cultivars increased significantly, and anaerobic respiration
      accelerated. The ethanol fermentation activity was higher in the seedling roots
      of hypoxia-tolerant cultivar Lubachun No. 4 than in those of hypoxia-sensitive
      cultivar Zhongnong No. 8, while lactate fermentation activity had an opposite
      trend. Comparing with treatment hypoxia, hypoxia plus D -arginine decreased the
      Put, Spd and Spm contents in roots significantly, enhanced the activities of
      alcohol dehydrogenase (ADH) and lactate dehydrogenase (LDH) and the contents of
      ethanol and lactate, and inhibited plant growth. Exogenous Put application
      lessened the effects of D-arginine. Higher level of polyamines in roots could
      have great benefits for cucumber seedlings to improve their resistance to hypoxia
      stress.

PMID- 17450744
TI  - [Effects of DMPP-compound fertilizer on greenhouse celery growth and nutritional
      quality].
AB  - A field study with greenhouse celery (Apium graveolens L. ) showed that compared
      with basal application of ordinary compound fertilizer, one-time basal
      application of DMPP-compound fertilizer ( ENTEC , 12-12-17) at the rates of 67. 5
      kg N x hm(-2) and 54. 0 kg N x hm(-2) increased the yield by 5. 78% and 10. 14% ,
      respectively. The application of ENTEC also improved the nutritional quality of
      edible parts, e. g. , the Vc, amino acid, soluble sugar, N and P contents
      increased, while nitrate content decreased. Compared with basal plus side
      dressing applications, appropriately reducing the application rate and times of
      ENTEChad more beneficial effects on celery yield and quality, and reduced the
      production costs. ENTEC could suppress the transformation of soil NH4+ -N to NO3 
      -N effectively, and thus, its application could retain soil residual N more in
      NH4+ -N than in NO3- -N form after celery harvested, resulting in a reduction of
      nitrate leaching.

PMID- 17450745
TI  - [Mechanisms of high temperature-induced Pseudoperonospora cubensis resistance of
      cucumber].
AB  - This paper studied the effects and control efficiency of high temperature on the
      pathogenicity and occurrence of Pseudoperonospora cubensis. The results showed
      that the P. cubensis resistance of cucumber was most obvious after treated at 40
      degrees C for 2 h or at 45 degrees C for 1 h, with the control efficiency being
      58. 40% and 45. 81% at the forth day, and 39. 35% and 37. 65% at the sixth day
      after P. cubensis inoculation, respectively. Under high temperature, the
      activities of peroxidase (POD), phenylalanine ammonia lyase (PAL) , chitinase
      (Cht), beta-1,3-glucanase (Glu) in cucumber leaf were significantly higher, and
      large amount of lignin was deposited on the cell wall of leaf tissue, indicating
      that after treated with high temperature, cucumber plant manifested an induced P.
      cubensis resistance.

PMID- 17450746
TI  - [Changes of oviposition preference of diamondback moth after experiencing a neem
      based repellent/deterrent BIOACT-T].
AB  - For the adults of phytophagous insects, their experience of non-host plant
      originated repellent/deterrent may produce habituation or induced preference to
      it. In this study, the experience-induced changes in oviposition responses of
      diamondback moth Plutelle xylostella L. to a neem-based repellent BIOACT-T EC508
      were examined in laboratory. 2-6 days old female moths were offered with 2--6
      times or 2-6 days experience of the repellent, and their ovipostion preference to
      untreated and BIOACT-treated Chinese cabbages were evaluated. The results showed
      that BIOACT had a strong repellent effect to all of the naive 2-6 days old
      females, that only laid approximately 10% of their eggs on BIOACT-treated plants.
      As for the 2, 4 and 6 days old females who experienced 2 times or 2 days, 4 times
      or 4 days, and 6 times or 6 days of BIOACT, their mean oviposition rate on BIOACT
      treated plants increased to 17% , 21%--24% , and 29% , respectively,
      demonstrating that this experience of the females induced their habituation or
      preference to BIOACT, and consequently, the repellent effect of BIOACT decreased.
      However, there were substantial variations in the experience-induced changes of
      oviposition preference among the individuals of the moth.

PMID- 17450747
TI  - [Effects of Tagetes erecta extracts on glutathione S-transferase and protease
      activities and protein content in Tetranychus viennensis].
AB  - With in vivo and in vitro Tagetes erecta roots under light and dark as test
      materials, this paper studied the effects of their extracts on the glutathione S
      transferase and protease activities and protein content in Tetranychus
      viennensis. The results showed that the chloroform extract of T. erecta roots had
      the highest light-activated activity, followed by water extract, and methanol
      extract. After treated with chloroform extract, the glutathione S-transferase and
      protease activities in T. viennensis increased markedly, while its protein
      content decreased obviously. The variation degree of T. viennensis protease
      activity and protein content was significantly higher when the chloroform extract
      came from the T. erecta roots under light, suggesting that there existed active
      matters in the extract, which could promote the activation of protease, and thus,
      the decomposition of protein in T. viennensis. The bioactivity of T. erecta
      metabolites was mainly of light-activated one.

PMID- 17450748
TI  - [Effects of Caenorhabditis elegans on Bacillus subtilis number and activity and
      soil nitrogen mineralization under different soil moisture conditions].
AB  - The study with gnotobiotic microcosm showed within the range of test soil
      moisture contents, the feeding activity of Caenorhabditis elegans on Bacillus
      subtilis promoted the latter' s proliferation, and enhanced soil respiration
      significantly. The increment of B. subtilis number varied with soil moisture
      content, and decreased in the order of 23% > 17% > 28% . The interaction of C.
      elegans and B. subtilis increased the contents of soil mineral N and NH4 + -N
      significantly, indicating that soil nitrogen mineralization was markedly
      promoted. A higher nitrogen mineralization rate was observed under 23% soil
      moisture content.

PMID- 17450749
TI  - [Abundance and biomass of meiobenthos in Southern Yellow Sea in winter].
AB  - A two cruises investigation on the meiobenthos in the continental shelf of
      Southern Yellow Sea was made in January 2003 and January 2004. The results showed
      that the average abundance of meiobenthos was (954.20 +/- 269.47) ind x 10 cm(-2)
      and ( 1 186.12+/- 486.07) ind x 10 cm(-2), and the biomass was (954.38+/-403.93)
      microg x10 cm(-2) and (1 120.72+/-487.21 ) mg x 10 cm(-2) in January 2003 and
      January 2004, respectively, with no significant difference observed. A total of
      twenty meiobenthic groups were identified. Free-living marine nematodes was the
      most dominant group in abundance, with a relative dominance of 87% in 2003 and
      90% in 2004, followed by benthic harpacticoids copepoda, polychaeta and
      kinorhyncha. In terms of biomass, the dominant groups were nematoda (34% -38%),
      polychaeta (25% -33%), ostracoda (9% -22%) and copepoda (8%). 96. 64% of the
      meiobenthos distributed in the top 0-5 cm of sediment, while 72. 48% of nematode
      and 89. 46% of copepoda were in the top 0-2 cm of the sediment. Meiobenthos
      biomass had significant correlation with the sand and silt contents of sediment
      and the content of Chl-a. The species composition and biodiversity analyses of
      six representative stations indicated that there were three meiobenthos
      communities in the study area, i. e. , inshore, cold waters mass, and
      transitional communities.

PMID- 17450750
TI  - [Effects of different concentration ammonium-n on Hydrilla verticillata
      antioxidant enzymes under Cd stress].
AB  - In this paper, submersed plant Hydrilla verticillata was cultivated in a 1/10
      Hoagland culture medium added with different concentration NH4 + -N (0, 0. 5, 2.
      0, 4. 0 mg x L(-1)) and 10 mg x L(-1) cadmium to study the effects of NH4 + -N on
      H. verticillata growth and its antioxidant enzyme system under Cd stress, and
      approach the degradation mechanism of submersed macrophyte in eutrophic and
      polluted water bodies. The results showed that under 10 mg x L(-1) Cd stress, the
      chlorophyll content of H. verticillata decreased obviously, and SOD and POD
      activities increased first but declined then. NH4 + -N accelerated the stress
      effect of Cd. Under 0. 5 h joint stress of Cd and NH4 + -N, SOD activity
      increased significantly, while such an increase needed 3 hours under single Cd
      stress. Relative to chlorophyll and protein, antioxidant enzyme system was an
      early sensitive index, and SOD was more sensitive than POD. After two days
      exposure to Cd plus NH4 -N, H. verticillata was mainly stressed by Cd, and NH4+ 
      N stress could be neglected.

PMID- 17450751
TI  - [Dynamics of Cd adsorption on rice seedlings root surface with iron coating and
      Cd uptake by plant].
AB  - In a water culture experiment, rice seedlings were grown in a nutrient solution
      containing 10 micromol Cd x L(-1), and harvested after different durations of
      growth. Two treatments were installed, i. e. , adding 50 mg Fe2+ x L(-1) to
      induce the formation of iron coating on seedlings root surface (treatment Fe50),
      and the control. The study on the dynamics of the Cd adsorption on root surface
      and of the Cd uptake by plant showed that both in the treatment Fe50 and in the
      control, the amount of adsorbed Cd on root surface was the highest in the first 2
      hours, decreased dramatically then and remained relatively stable thereafter,
      while the Cd concentrations in roots and shoots increased slowly within the first
      8 hours and rapidly then. The increment of Cd concentrations in roots and shoots
      was smaller in treatment Fe50 than in the control, and the amounts of adsorbed
      and absorbed Cd also showed the same picture, suggesting that the iron coating on
      rice root surface had little effect on the dynamics of Cd content in different
      parts of rice seedlings, and the reduced Cd uptake in treatment Fe50 was probably
      relevant with the Fe concentration in roots.

PMID- 17450752
TI  - [Effects of dissolved organic matter on phenanthrene adsorption by soil].
AB  - This paper studied the effects of exotic and native dissolved organic matter
      (DOM) on the phenanthrene adsorption by three soils differed in soil organic
      carbon content (foc). The exotic DOM came from decayed rice straw, while the
      native DOM was extracted from the test soils. In all cases, the adsorption of
      phenanthrene by treated soils could be well described with linear-type model, and
      there was a positive correlation between adsorption coefficient (Kd) and foc
      Compared with the control, the Kd value of test soils after native DOM removed
      was increased by 7. 08% -21. 4% , and the increment (deltaKd) was positively
      correlated with fo,, indicating that the presence of soil native DOM impeded the
      phenanthrene adsorption by soil. The effects of exotic DOM on phenanthrene
      adsorption had a close relation with its added concentration in soil-water
      system. Within the range of 0-106 mg DOC x L(-1) , the K, value increased first,
      and then decreased with the increase of added exotic DOM concentration. Lower
      concentrations of added exotic DOM promoted the phenanthrene adsorption by soil,
      while higher concentrations ( I> or =52 mg DOC x L(-1)) of it obviously impeded
      this adsorption. These effects of exotic and native DOM on soil phenanthrene
      adsorption were considered to be related to the association of phenanthrene with
      DOM in solution, and the ' cumulative adsorption effect' between soil solid and
      aqueous phases.

PMID- 17450753
TI  - [Research advance in seed germination of desert woody plants].
AB  - This paper reviewed the research methods of desert woody plants seed germination,
      and the effects of internal and external ecological factors on it. Most
      researchers use incubator and artificial climate chamber to dispose the seeds,
      while field investigation was few involved. Seed dormancy is the important
      physiological factor affecting germination, while seed size, mass and color are
      closely correlated with its maturity and vigor. The poor permeability of seed
      capsule is a barrier that restrains the germination, which can be weakened or
      eliminated by shaving, cutting, treating with low temperature, and dipping in
      chemical reagent, etc. Seed water content has a close correlation with its
      storage life and water-absorbing capability. Suitable temperature is the
      prerequisite of seed germination, while changing temperature can accelerate the
      germination. Soil moisture content is a limiting factor, while illumination is
      not so essential to the seed germination of most desert woody plants. Sand
      burying plays an important role in the seed germination through regulating
      illumination, temperature, and soil moisture content. Salinity stress restrains
      the seed germination of desert woody plants observably. In further studies, the
      effects of multi-factors and the eco-physiological and molecular biological
      mechanisms of germination should be more concerned.

PMID- 17450754
TI  - [Research advances in vulnerability assessment of natural ecosystem response to
      climate change].
AB  - Climate change with global warming as the sign has been caught great attention by
      the governments, international organizations, and scientists in the world. Human
      society and natural ecosystem are both exposed to climate change, and more and
      more people are waked up by its increasing harm. Vulnerability analysis and
      assessment are the key and basis for adapting and mitigating climate change,
      being the highlight in the research fields of climate change and ecology in
      recent years. The vulnerability assessment of climate change is being carried out
      in various research fields and on different scales, and much progress has been
      made. This paper introduced the concept of vulnerability, and summarized the
      research progress in vulnerability assessment of climate change, with the focus
      on the frame and methodology of vulnerability assessment of natural ecosystem
      response to climate change. The existed problems and future prospects in this
      research area were also discussed.

PMID- 17450755
TI  - [Flight behaviors of Bemisia tabaci and corresponding IPM strategies].
AB  - Bemisia tabaci, a pest insect with stronger capabilities of flying and host plant
      exploitation, is capable of flying 150 m high and over a distance as far as 7 km,
      but hardly flies higher than 0. 5 m and long distance in food-abundant areas. B.
      tabaci has the characteristics of both searching-and migrating flying, which
      enable it to exploit and locate on suitable hosts. Up to now, no oogenesis-flight
      syndrome of B. tabaci has been detected. Visual spectrum, air temperature and
      relative humidity, host quality, and wind speed are the main factors affecting
      the flight behavior of B. tabaci. In this paper, the flying capability of B.
      tabaci and the factors affecting its flight behavior were summarized, and the
      corresponding IPM strategies in the areas where B. tabaci could not overwintering
      in open field were discussed.

PMID- 17450756
TI  - [Horizontal subsurface flow constructed wetland models].
AB  - As a new treatment technology, constructed wetland plays an important role and
      has broad prospects in water pollution control and environmental restoration. Its
      designing artifice is getting progress owing its increasing application in
      wastewater treatment coupling with the increasingly strict water quality
      standards. From the aspects of hydrodynamics, contaminants degradation dynamics
      and parameters uncertainty, this paper gave a systematic review on the horizontal
      subsurface flow constructed wetland models, including load approach, regression
      equation, first-order k - C* model and its reformed forms, and dynamic
      mechanistic models. Based on the comparison of the assumptions and methodologies
      of the models, the intrinsic relationships in the development of horizontal
      subsurface flow constructed wetland models were analyzed, and the main issues of
      their application in constructed wetland design were indicated, with the
      perspectives in this field discussed.

PMID- 17450757
TI  - [Molecular genetic diversity of Fujian domestic duck breeds].
AB  - By using 28 micro-satellite markers with better polymorphism, this paper studied
      the genetic diversity of four Fujian provincial domestic duck breeds Jinding,
      Putian black, Liancheng white, and Shanma. According to the alleles frequencies,
      the polymorphic information content, average heterozygosity, anaqular genetic
      distance (DA) and Nei' s standard genetic distance (DS) for each breed were
      calculated. Based on DA and DS, four dendrograms were obtained by neighbor
      joining (NJ) and UPGMA methods. The results showed that the average
      heterozygosity of the four duck breeds was 0. 5353, indicating that the
      protection of the genetic diversity of these breeds should be strengthened. The
      orders of the two types of genetic distances among the breeds were accordant, and
      the dendrograms were the same, reflecting that much more micro-satellite loci
      should be adopted to obtain more universal conclusions when the genetic diversity
      was analyzed. The phylogenetic relationships among the four duck breeds were in
      accordance with their economic types and ecological localities.

PMID- 17450758
TI  - [Geostatistic analysis of spatial pattern of Fruhstorferiola tonkinensis Will].
AB  - By the methods of geostatistics, this paper studied the spatial pattern of
      Fruhstorferiola tonkinensis nymphs in mulberry fields of north Guangdong. The
      results showed that the semivariogram of F. tonkinensis nymphs at all development
      stages could be described by spherical model, implying an aggregative
      distribution, and the range of their spatial correlation was 1. 973, 1. 968, 2.
      169, 2. 302 and 4. 307 m from 1st to 5th instars. Based on the information
      obtained from investigation site, the isoclines maps of the instars were created
      by the geostatistical software Surfer 8. 0 with Kriging interpolation, and the
      resulting maps gave a clear indication about the spatial patterns of the instars.
      Unlike other locusts, the younger instars of F. tonkinensis had an aggregative
      distribution, while the elder ones were dispersive in distribution.

PMID- 17450759
TI  - [Guidelines and therapeutic protocols: relevance for the quality of
      prescription].

PMID- 17450760
TI  - [Biologic agents in juvenile idiopathic arthritis].

PMID- 17450761
TI  - Biologic therapies in juvenile idiopathic arthritis: why and for whom?
AB  - With greater understanding of pathophysiological, genetic and environmental
      influences on juvenile arthritis, there is an opportunity to develop new targets
      for therapy and greater control of disease. Early, aggressive control of
      arthritis is essential in order to prevent long-term disability. For those
      children that are resistant to standard therapy, new and exciting alternative
      medications are emerging. However, continued research is needed to gain a greater
      understanding of immunological and genetic profiles of the disease. Pharmaco
      vigilance is essential to establish efficacy and side effect profiles.
      Physiotherapy, occupational therapy, nursing issues, and psychology remain
      integral to the management of JIA, along with liaison with ophthalmology,
      orthopaedic and dental colleagues. This article reviews the current biologic
      treatment options available for children with arthritis and the evidence base
      that supports their use.

PMID- 17450762
TI  - Capillarosecopic patterns in rheumatic diseases.
AB  - Nailfold capillaroscopy (NVC) is a simple, non-invasive, inexpensive and useful
      method for the analysis of microvascular abnormalities found in several rheumatic
      disorders. The well-known Raynaud's phenomenon is a clinical condition that
      should promptly lead to a microvascular analysis, in order to distinguish its
      primary form (functional, not disease associated) from the secondary Raynaud's
      phenomenon (disease associated). NVC has an exceptional predictive value in this
      early distinction, and this may be the best advantage this technique can offer.
      Microvascular damage is a typical feature of Systemic Sclerosis (SSc) and more
      than 95% of the patients present architectural disorganization, giant
      capillaries, haemorrhages, loss of capillaries, avascular areas and
      neovascularization, as main microvascular abnormalities. These sequential
      capillaroscopic changes characterize the "scleroderma pattern" and reflect the
      SSc microangiopathy. In dermatomyositis and undifferentiated connective tissue
      disease the capillaroscopic aspects are generally named as "scleroderma-like
      pattern". Capillaroscopy changes have also been found in other systemic rheumatic
      diseases such as Systemic Lupus Erythematosus, Antiphospholipid Syndrome and
      Sjogren's Syndrome, further epidemiological and clinical studies are needed to
      better characterize and standardize nailfold capillaroscopy patterns in these
      disorders.

PMID- 17450763
TI  - [Guidelines for the use of biologic therapies in rheumatoid arthritis--December
      2006 update].
AB  - The authors present the revised version of the Portuguese Society of Rheumatology
      (SPR) guidelines for the treatment of rheumatoid arthritis (RA) with biological
      therapies. In these guidelines the criteria for introduction and maintenance of
      biological therapies were discussed as well as the contra-indications and
      procedures in case of non-responders. Biological treatment is indicated in RA
      patients with a disease activity score 28 (DAS 28) superior to 3,2 despite
      treatment with 20mg/week of methotrexate (MTX) for at least 3 months or, if such
      treatment is not possible, refractory to 6 months of other conventional disease
      modifying drug or combination therapy. It is also considered the hypothesis of
      starting a biological treatment in RA patients treated by the previous regimes
      with a DAS28 score between 2,6 and 3,2 and a significative functional or
      radiological worsening. The follow-up should be performed each 3 months. The
      response criteria, at the end of the first 3 months of treatment, is a decrease
      of 0,6 in the DAS28 score. After 6 months of treatment response criteria is
      defined as follows: for those with an initial DAS28 score superior to 5,1, a
      reduction of the DAS28 score below 4 is required; for those with an initial DAS28
      score inferior to 5,1, a reduction of the DAS28 score below 2,6 or between 2,6
      and 3,2 without a significative functional or radiological worsening is required.
      Non-responders, in accordance to the Rheumatologist's clinical opinion, should
      try a switch to other tumour necrosis factor alpha antagonist or to rituximab.

PMID- 17450764
TI  - [Guidelines for prescribing and monitoring biologic therapies in juvenile
      idiopathic arthritis].
AB  - The Pediatric RheumatologyWorking Group of the Portuguese Society of Rheumatology
      recommends the use of biological treatments in children with polyarticular course
      Juvenile Idiopathic Arthritis (JIA) with active disease (5 or more active joints)
      refractory to subcutaneous or intramuscular methotrexate (MTX) 15 mg/m(2)/week
      during 3 to 6 months. If toxicity occurs, or if there is contraindication for the
      use of MTX in this optimum dose, biological treatment can be started, as a first
      option, or the use of other conventional Disease ModifyingAnti Rheumatic Drug
      (DMARD) either alone or in combination with MTX might be considered. Prior to
      starting treatment, children should be screened for latent tuberculosis through
      clinical evaluation, chest X ray and PPD skin test. The suspension of the
      biological treatment should be considered if the American College of Rheumatology
      (ACR) definition of improvement in JIA is not fulfilled in two consecutive visits
      3 months apart. Etanercept is the only biological agent currently approved for
      JIA in Portugal. In refractory cases the use of infliximab is accepted, in
      accordance with preliminary published evidence. In case of systemic
      manifestations of JIA refractory to conventional treatment, anakinra can be
      considered.

PMID- 17450765
TI  - [Recommendations for the diagnosis and management of osteoporosis].
AB  - This article presents the guidelines for the management of osteoporosis
      established by the Portuguese Society of Rheumatology and the Portuguese Society
      of Metabolic Bone Diseases. The document is the result of the consensus achieved
      after systematic review of the literature and open discussion in nationa meetings
      of both societies of draft documents presented by the authors. The
      recommendations include aspects related to diagnosis, clinical evaluation,
      prevention, treatment and monitoring of post-menopausal and male osteoporosis.
      The guidelines aim to achieve the reduction of osteoporotic fractures throug
      validated clinical practices that will allow the correct use of diagnostic and
      therapeutic resources. The consensus will be reviewed as needed whenever new
      scientific evidence is available.

PMID- 17450766
TI  - [Macrodystrophia lipomatosa. A rare disease with rheumatic manifestations].
AB  - The author presents the case of a 32-year-old woman with the diagnosis of
      Macrodystrophia Lipomatosa associated with carpal tunnel syndrome.
      Macrodystrophia Lipomatosa is a rare form of localized gigantism characterised by
      an abnormal overgrowth of the mesenchymal elements of one or more digits. For the
      rheumatologist this disease has interest due the possibility of musculoskeletal
      complaints, namely compression of the neurovascular structures and local
      degenerative articular disease.

PMID- 17450767
TI  - [Low back pain with 'red flags': a case of spondylodiscitis].
AB  - Spondylodiscitis is a serious clinical entity. Despite the decrease in mortality
      from about 25% in the pre-antibiotic era to near 5%, it remains significant and
      the associated morbidity is still relevant. The rate of residual neurological
      deficits among survivors is around 7%. In 30% of patients some related symptoms
      persist, the most important being pain. The authors report the case of a 74-year
      old male patient with recent onset low back pain, which caused considerable
      disability. With this work the authors intend to alert to the fact that in a
      patient with a common symptom such as low back pain, the presence of "red flags"
      requires a quick investigation and diagnosis in order to prevent serious damage.

PMID- 17450768
TI  - [Systemic lupus erythematosus and anaemia].
AB  - The authors report the case of a 48-years-old Caucasian women, with a previous
      diagnosis of systemic lupus erythematosus characterized by asthenia, fever, skin
      rash, alopecia, Raynaud's phenomenon, arthritis, pericardial effusion,
      interstitial pulmonary involvement, diffuse proliferative glomerulonephritis with
      crescents and anemia. The presence of severe anemia refractory to high doses of
      glucocorticoids (1 mg/ /Kg/day), iron therapy and blood transfusions, associated
      with a low reticulocyte count determined the execution of a bone marrow
      aspiration, biopsy and immunophenotyping, which were compatible with the
      diagnosis of Myelodysplastic Syndrome. The treatment with erythropoietin (5.000U
      3x/week) and cyclophosphamide pulses (1 gr/m(2) month) induced complete
      regression of morphologic bone marrow changes and anemia. The main causes of
      anemia in lupus patients are discussed.

PMID- 17450769
TI  - [Ptotic Baker's cyst].

PMID- 17450770
TI  - Engineering protein and peptide building blocks for nanotechnology.
AB  - The tremendous diversity in the structure and function of proteins has stimulated
      intense interest in using them for nanotechnology applications. In this review,
      we discuss recent developments in the engineering of proteins and peptides for
      the design and construction of functional and structural elements of nanodevices.
      We begin with a short discussion highlighting the differences between chemical
      and biological synthesis of proteins and peptides. Subsequently, we review recent
      applications of proteins and peptides as molecular motors, transducers,
      biosensors, and structural elements of nanodevices. We supplement this review
      with highlights of our own work in the areas of peptide-based transducers for
      stand-alone and intra-molecular applications. This is followed by a short
      discussion of nanotechnology safety issues, and how proteins and peptides may
      enable the development of biocompatible nanomaterials. The future outlook for
      protein and peptide-based nanomaterials is then discussed, with an eye toward the
      significant impact of improved computational techniques on the field.

PMID- 17450771
TI  - How to assess the risks of nanotechnology: learning from past experience.
AB  - Nanotechnology may yield a plethora of beneficial applications, but it can also
      be expected to present risks. The challenge is to anticipate and reduce
      environmental and health risks or, at a minimum, identify and deal with such
      threats once they begin to become evident. Past experience, particularly with the
      fuel additive MTBE (methyl tertiary butyl ether), provides valuable guidance on
      how to assess the potential risks of nanotechnology using a comprehensive
      environmental assessment approach, which combines a product life-cycle
      perspective with the risk assessment paradigm. This systematic approach can serve
      not only to guide the development of a research strategy for assessing the risks
      of nanotechnology but possibly even help avert unintended consequences of
      nanotechnology.

PMID- 17450772
TI  - Production of nanopatterns by a combination of electron beam lithography and a
      self-assembled monolayer for an antibody nanoarray.
AB  - We report on a flexible method of producing antibody (IgG) nanopatterns by
      combining electron beam (EB) lithography and a perfluorodecyltriethoxysilane
      (FDTES) self-assembled monolayer (SAM). Using EB lithography of the FDTES SAM, we
      easily fabricated IgG patterns with feature sizes on the order of 100 nm. The
      patterned IgG retained its ability to interact specifically with an anti-LgG. The
      influence of different concentrations of the IgG and anti-IgG on the resulting
      fluorescent IgG arrays was investigated. These IgG nanopatterns appeared to be
      remarkably well controlled and showed almost no detectable nonspecific binding of
      proteins on a hydrophobic SAM under a suitable incubation condition,
      characterized by atomic force microscopy, and epi-fluorescence microscopy. The
      technique enables the realization of high-throughput protein nanoscale arrays
      with high specificity.

PMID- 17450773
TI  - Characterization of different sequences of DNA on si substrate by atomic force
      microscopy and gold nanoparticle labeling.
AB  - In this paper, different sequences of single-strand DNA modified on Si substrate
      were studied taking advantages of the high resolution of atomic force microscopy
      (AFM) and signal enhancement of gold nanoparticles. Two sequences of single
      strand DNA, as a model, were immobilized on Si substrate and hybridized with
      their sequence-complementary DNA molecules modified respectively with two sizes
      of gold nanoparticles. The surface of Si substrate was characterized through
      detecting the size and coverage of gold nanoparticles by AFM. Results
      demonstrated that different sizes of gold nanoparticles represented different
      sequences of DNA immobilized on the substrate. Density and distribution of DNA on
      Si substrate can be investigated by AFM imaging using gold nanoparticles as
      topographic markers. Compared to other sensitive methods such as fluorescence
      energy transfer, X-ray photoelectron, and radiolabeling experiments, this
      approach is advantageous in terms of high spatial resolution in sub-micrometer
      scale. This new method will be beneficial in the characterization of DNA
      immobilized on chip surfaces.

PMID- 17450774
TI  - Systematic studies of a self-assembling peptide nanofiber scaffold with other
      scaffolds.
AB  - A designer self-assembling peptide nanofiber scaffold has been systematically
      studied with 10 commonly used scaffolds in a several week study using neural stem
      cells (NSC), a potential therapeutic source for cellular transplantations in
      nervous system injuries. These cells not only provide a good in vitro model for
      the development and regeneration of the nervous system, but may also be helpful
      in testing for cytotoxicity, cellular adhesion, and differentiation properties of
      biological and synthetic scaffolds used in medical practices. We tested the self
      assembling peptide nanofiber scaffold with the most commonly used scaffolds for
      tissue engineering and regenerative medicine including PLLA, PLGA, PCLA, collagen
      I, collagen IV, and Matrigel. Additionally, each scaffold was coated with laminin
      in order to evaluate the utility of this surface treatment. Each scaffold was
      evaluated by measuring cell viability, differentiation and maturation of the
      differentiated stem cell progeny (i.e. progenitor cells, astrocytes,
      oligodendrocytes, and neurons) over 4 weeks. The optimal scaffold should show
      high numbers of living and differentiated cells. In addition, it was demonstrated
      that the laminin surface treatment is capable of improving the overall scaffold
      performance. The designer self-assembling peptide RADA16 nanofiber scaffold
      represents a new class of biologically inspired material. The well-defined
      molecular structure with considerable potential for further functionalization and
      slow drug delivery makes the designer peptide scaffolds a very attractive class
      of biological material for a number of applications. The peptide nanofiber
      scaffold is comparable with the clinically approved synthetic scaffolds. The
      peptide scaffolds are not only pure, but also have the potential to be further
      designed at the molecular level, thus they promise to be useful for cell adhesion
      and differentiation studies as well as for future biomedical and clinical
      studies.

PMID- 17450775
TI  - Doxorubicin-CdS nanoparticles: a potential anticancer agent for enhancing the
      drug uptake of cancer cells.
AB  - A novel strategy of enhancing the drug uptake by cancer cells through the
      combination of anticancer drug doxorubicin with cadium sulfide (CdS)
      nanoparticles has been explored by using confocal fluorescence scanning
      microscopy as well as electrochemical studies, which demonstrates that CdS
      nanoparticles can readily conjugate with doxorubicin on the targeted cancer cells
      and facilitate the uptake of drug molecules in the human leukemia K562 cells.
      Besides, our observations also indicate that the aggregation of the leukemia
      cells occured when CdS nanoparticles were introduced into the relative target
      system together with doxorubicin, suggesting that the specific association of CdS
      nanoparticles with biologically active molecules on the surface of leukemia K562
      cells may change some biorecognition or signal transfer pathway among cancer
      cells. It is suggested that the competitive binding of CdS nanoparticles with
      accompanying anticancer drug to the membrane of leukemia K562 cells could
      efficiently prevent the drug release by the drug resistant leukemia cells and
      thus inhibit the relative multidrug resistance (MDR) of targeted cancer cells.

PMID- 17450776
TI  - Interfacial construction of gold nanoshells on 3-aminopropyl triethoxysilane
      modified ITO electrode surface for studying cytochrome b562 electrochemistry.
AB  - An interface of gold nanoshells (GNSs) was constructed on the surface of the 3
      aminopropyl triethoxysilane (APTES) modified ITO glass substrates by a simple
      self-assemble method to form the GNSs-coated ITO electrode. UV-vis spectroscopy,
      scanning electron microscopy (SEM), and cyclic voltammetry were used to
      characterize the GNSs interface architectures. SEM and UV-vis spectroscopy showed
      that an interconnected and stable GNSs interface was formed on the APTES modified
      ITO glass substrate. The cytochrome b562 (Cyt b562) was selected to observe
      electron transfer reactions of redox protein at the GNSs-coated ITO electrodes.
      Quasi-reversible electrochemistry of Cyt b562 was obtained and its
      electrochemical behaviors were discussed.

PMID- 17450777
TI  - Preparation and characterization of grafted collagen-multiwalled carbon nanotubes
      composites.
AB  - This paper describes a new class of composite materials designed by combining
      multiwalled carbon nanotubes (MWCNTs) and grafted collagen matrix. These
      materials show high mechanical capabilities by taking advantage of the favorable
      mechanical characteristics of MWCNTs. Furthermore, doping carbon nanotubes into
      grafted collagen matrix results in a substantial improvement of thermal stability
      and infrared emissivity. Thus these materials possess potential applications in
      some fields such as biomedicine and infrared camouflage.

PMID- 17450778
TI  - Mechanical characterization of cellulosic thecal plates in dinoflagellates by
      nanoindentation.
AB  - Dinoflagellates constitute an important group of microorganisms. Symbiotic
      dinoflagellates are responsible for the primary production of coral reef
      ecosystems and the phenomenon of their demise is known as "coral bleaching."
      Blooming of the planktonic dinoflagellates is the major cause of "red tides."
      Many dinoflagellates have prominent membrane-bound thecal plates at their cell
      cortices. These thecal plates have high cellulose content and are biologically
      fabricated into various shapes. However, the mechanical properties of theca have
      not previously been characterized; understanding these properties, including
      hardness and elastic modulus, will give insights into the ecological significance
      and biotechnological potential of bio-fabricated structures. A series of
      nanoindentation tests were performed on various locations of cellulosic thecal
      plates isolated from the dinoflagellates Alexandrium catenella and Lingulodinium
      polyedrum. Despite having transparent properties, thecal plates possess
      mechanical properties comparable to softwood cell walls, implicating their role
      as a protective cell covering. Consistent measurements were obtained when
      indentation was performed at various locations, which contrasts with the high
      variability of cellulose microfibers from plant sources. The present study
      demonstrated the novel properties of this potential new source of cellulose.

PMID- 17450779
TI  - Synthesis and characterization of TiO2 nanotube/hydroquinone hybrid structure.
AB  - It is shown that 1,4-benzenediol (hydroquinone) and TiO2 nanotubes can form a
      hybrid structure that is stable in aqueous environment. The incorporation of
      hydroquinone restores the local structure of nanotubes to anatase-like as
      evidenced by Raman spectroscopy. Subtle overall structural changes take place
      upon annealing of the hybrid structure contributing to its stability. The hybrid
      system shows a broad optical absorption peak extending significantly beyond 700
      nm with potential applications in photocatalysis and photoelectrochemistry.

PMID- 17450780
TI  - A single-source solid-precursor method for making eco-friendly doped
      semiconductor nanoparticles emitting multi-color luminescence.
AB  - A novel synthesis method is presented for the preparation of eco-friendly, doped
      semiconductor nanocrystals encapsulated within oxide-shells, both formed
      sequentially from a single-source solid-precursor. Highly luminescent ZnS
      nanoparticles, in situ doped with Cu(+)-Al3+ pairs and encapsulated with ZnO
      shells are prepared by the thermal decomposition of a solid-precursor compound,
      zinc sulfato-thiourea-oxyhydroxide, showing layered crystal structure. The
      precursor compound is prepared by an aqueous wet-chemical reaction involving
      necessary chemical reagents required for the precipitation, doping and inorganic
      surface capping of the nanoparticles. The elemental analysis (C, H, N, S, O, Zn),
      quantitative estimation of different chemical groups (SO4(2-) and NH4(-)) and
      infrared studies suggested that the precursor compound is formed by the
      intercalation of thiourea, and/or its derivatives thiocarbamate (CSNH2(-)),
      dithiocarbamate (CS2NH2(-)), etc., and ammonia into the gallery space of zinc
      sulfato-oxyhydroxide corbel where the Zn(II) ions are both in the octahedral as
      well as tetrahedral coordination in the ratio 3 : 2 and the dopant ions are
      incorporated within octahedral voids. The powder X-ray diffraction of precursor
      compound shows high intensity basal reflection corresponding to the large lattice
      plane spacing of d = 11.23 angstroms and the Rietveld analysis suggested
      orthorhombic structure with a = 9.71 angstroms, b = 12.48 angstroms, c = 26.43
      angstroms, and beta = 90 degrees. Transmission electron microscopy studies show
      the presence of micrometer sized acicular monocrystallites with prismatic platy
      morphology. Controlled thermolysis of the solid-precursor at 70-110 degrees C
      leads to the collapse of layered structure due to the hydrolysis of interlayer
      thiourea molecules or its derivatives and the S2- ions liberated thereby reacts
      with the tetrahedral Zn(II) atoms leading to the precipitation of ZnS
      nanoparticles at the gallery space. During this process, the dopant ions situated
      at octahedral voids gets incorporated into the nano-ZnS lattice and results in
      bright photoluminescence. On further heat treatment above 1100 degrees C, the
      corbel zinc-oxyhydroxide sheets undergo dehydroxylation to form ZnO which
      eventually encapsulates the ZnS nanoparticles at the gallery leading to
      significant enhancement in the luminescence quantum efficiency, up to
      approximately 22%. The emission color of thus formed nano-ZnS/micro-ZnO
      composites could be tuned over wide spectral ranges from 480 to 618 nm and the
      spectral changes are attributed to a number of factors including lattice defects,
      Cu(+)-Al3+ dopant-pairs and iso-electronic oxygen in nano-ZnS and oxygen-vacancy
      or -interstitial centers in non-stoichiometric ZnO.

PMID- 17450781
TI  - Fabrication and photoluminescent properties of Gd2O3 : EU3+ nanowires in AAO
      template.
AB  - Uniform Gd2O3 : Eu3+ nanowires were fabricated by using anodic aluminum oxide
      template (AAO). The spectral measurements indicate that with the increasing
      annealing temperature the excitation band of Eu3+ in Gd2O3 : Eu3+ nanowires/AAO
      shifted blue, the intensity ratio of 5D0-7F2 to 5D0-7F1, decreased, and the
      lifetime became longer. In the sample annealed at 1000 degrees C two spectral
      components, the sharper and broader lines were identified, corresponding to two
      different local environments, the Eu3+ ions in cubic phase and in amorphous
      phase, respectively. The 5D0-7F1 transitions of Eu3+ ions in cubic phase had
      longer lifetime than that in amorphous phase. In contrast to the lifetime of the
      5D0-7F(j) transitions in the bulk, that in Gd2O3 : Eu3+/AAO composite films
      increased due to influence of the surrounding media (AAO).

PMID- 17450782
TI  - Synthesis, characterization, and green luminescence in ZnO nanocages.
AB  - In this paper, we report the synthesis, characterization and observation of green
      luminescence in ZnO nanocages. A novel low temperature solution-based technique
      has been developed for growing highly porous ZnO nano-cages from coarse ZnO
      precursor powders. Various samples, prepared in this study, were characterized
      using several different characterization tools such as X-ray diffraction,
      Scanning Electron Microscopy, Energy Dispersive X-ray Spectroscopy, Raman,
      Photoluminescence and Optical Transmission Spectroscopy. It has been shown that
      ZnO nanocages exhibit green luminescence, with PL data showing a broad green peak
      at 510 nm. The shift and broadening in the luminescence peaks are understood to
      arise because of the onset of deep level defects in the system.

PMID- 17450783
TI  - Optical properties of zigzag twinned geometry of Zn2SnO4 nanowires.
AB  - High-density single-crystalline Zn2SnO4 nanowires have been successfully
      synthesized by using a simple thermal evaporation method by heating a mixture of
      ZnO and SnO2 nano powders. The products in general contain various geometries of
      wires, with an average diameter of 80-100 nm. These nanowires are ultra-long, up
      to 100 microns. The transmission electron microscopy study showed that these
      nanowires exhibited zigzag twinned geometry, and grow along the (111) direction.
      Low-temperature photoluminescence properties of the nanowires were measured,
      showing a strong green emission band at about 515 nm and a weak peak
      corresponding to UV emission at about 378 nm, which have not been reported
      before.

PMID- 17450784
TI  - Preparation of orpiment nanoparticles and their cytotoxic effect on cultured
      leukemia K562 cells.
AB  - An investigation has been made into the antitumor effect on K562 cells of
      orpiment nanoparticles which were prepared chemically and analyzed by
      transmission electron microscope and energy dispersive spectrometry (EDS). Methyl
      thiazolyl tetrazolium and flow cytometry assays were performed to examine their
      antitumor effect compared with that of traditional orpiment at various
      concentrations. The average diameters of the two types of orpiment nanoparticles
      prepared were 60 nm and 140 nm, respectively, and EDS identified that only
      orpiment was present. Orpiment nanoparticles greatly inhibited the proliferation
      of K562 cells by apoptosis, in a concentration-and time-dependent manner, much
      more effectively than traditional orpiment (p < 0.001). The survival ratio of
      cells treated with orpiment nanoparticles at 2, 4, 8, and 16 micromol/l after 72
      h was 23.0%, 10.1%, 3.2%, and 0.5%, respectively, much lower than 80.0%, 69.0%,
      52.3%, and 31.7% of cells treated with traditional orpiment at the corresponding
      concentration for 72 h. The IC50 of orpiment nanoparticles in K562 cells for 48 h
      was only 1.27 micromol/l, in comparison with 13.0 micromol/l of traditional
      orpiment. After treated with orpiment nanoparticles at 4, 8, and 16 micromol/l
      for 48 h, the apoptotic rate of cells was 11.55%, 20.70%, and 26.45%,
      respectively, but that in cells treated with traditional orpiment at the same
      concentration for 48 h was only 3.16%, 3.86%, and 6.46%, respectively. Thus,
      orpiment nanoparticles can produce a much better cytotoxic effect on cancer cells
      than that of traditional orpiment.

PMID- 17450785
TI  - In vitro and in vivo toxicity of CdTe nanoparticles.
AB  - Cadmium telluride (CdTe) nanoparticles exhibit strong and stable fluorescence
      that is attractive for many applications such as biological probing and solid
      state lighting. The evaluation of nanoparticle toxicity is important for
      realizing these practical applications. However, no systematic studies of CdTe
      nanoparticle toxicity have been reported. We investigated and compared the size-
      and concentration-dependent cytotoxicity of CdTe nanoparticles in human hepatoma
      HepG2 cells using the MTT assay. CdTe nanoparticles elicited cytotoxicity in a
      concentration- and size-dependent manner, with smaller-sized particles exhibiting
      somewhat higher potency. Lesser cytotoxicity of partially purified CdTe-Red
      particles (following methanol precipitation and resuspension) suggested that free
      cadmium ions may contribute to cytotoxicity. We also evaluated the acute toxicity
      of CdTe-Red particles following intravenous exposure in male rats (2
      micromol/kg). Few signs of functional toxicity or clinical (urinary or blood)
      changes were noted. Interestingly, motor activity was transiently reduced (2
      hours after treatment) and then significantly increased at a later timepoint (24
      hours after dosing). These studies provide a framework for further characterizing
      the in vitro and in vivo toxic potential of different types of CdTe nanoparticles
      and suggest that the nervous system may be targeted by these nanoparticles under
      some conditions.

PMID- 17450786
TI  - Facile fabrication of magnetic nanocomposites of ordered mesoporous carbon
      decorated with nNickel nanoparticles.
AB  - A magnetic nanocomposite of ordered mesoporous carbon (CMK-3) decorated with
      nickel nanoparticles was synthesized successfully by a simple chemistry method.
      Nickel nanoparticles were prepared and uniformly supported on ordered mesoporous
      carbon CMK-3 by reduction route with CMK-3 as a reducing agent at 673 K. The
      Ni/CMK-3 composite materials were characterized by powder X-ray diffraction,
      nitrogen sorption, and transmission electron microscopy. As-prepared nickel
      nanoparticles supported on CMK-3 were crystalline with a face-center-cubic phase
      and a size distribution ranging from 10 to 60 nm. The BET special surface area
      and pore volume of Ni/CMK-3 were as high as 797 m2 g(-1) and 0.72 cm3 g(-1),
      respectively. The formation mechanism of the nickel nanoparticles outside the
      surface of CMK-3 was preliminarily discussed. The hysteresis loops of the CMK-3
      decorated with nickel nanoparticles were measured by vibrating sample
      magnetometer (VSM), and the results showed that the composite was ferromagnetism
      with the saturated magnetization of 15 emu/g, and the coercivity value of 214 Oe.
      Furthermore, the application of Ni/CMK-3 as magnetically separable adsorbent for
      vitamin B2 was primarily examined in this study.

PMID- 17450787
TI  - Nanostructured films employed as sensing units in an "electronic tongue" system.
AB  - Nanostructured films of lignin (macromolecule extracted from sugar cane bagasse),
      polypyrrole (conducting polymer) and bis butylimido perylene (organic dye) were
      used in the detection of trace levels of fluorine (from H2SiF6), chlorine (from
      NaClO), Pb(+2), Cu(+2), and Cd(+2) in aqueous solutions. Langmuir monolayers on
      ultrapure water were characterised by surface pressure-mean molecular area (II-A)
      isotherms. Langmuir-Blodgett (LB) films were transferred onto gold interdigitated
      electrodes and used as individual sensing units of an electronic tongue system.
      Impedance spectroscopy measurements were taken with the sensor immersed into
      aqueous solutions containing the ions described above in different molar
      concentrations. Fourier transform infrared absorption (FTIR) was employed to
      identify possible interactions between the LB films and the analytes in solution,
      and no significant changes could be observed in the FTIR spectra of BuPTCD and
      Ppy. Therefore, the results for lignin point to an interaction involving the
      electronic cloud of the phenyl groups with the metallic ions.

PMID- 17450788
TI  - Carbon nanotube reinforced aluminum nanocomposite via plasma and high velocity
      oxy-fuel spray forming.
AB  - Free standing structures of hypereutectic aluminum-23 wt% silicon nanocomposite
      with multiwalled carbon nanotubes (MWCNT) reinforcement have been successfully
      fabricated by two different thermal spraying technique viz Plasma Spray Forming
      (PSF) and High Velocity Oxy-Fuel (HVOF) Spray Forming. Comparative
      microstructural and mechanical property evaluation of the two thermally spray
      formed nanocomposites has been carried out. Presence of nanosized grains in the
      Al-Si alloy matrix and physically intact and undamaged carbon nanotubes were
      observed in both the nanocomposites. Excellent interfacial bonding between Al
      alloy matrix and MWCNT was observed. The elastic modulus and hardness of HVOF
      sprayed nanocomposite is found to be higher than PSF sprayed composites.

PMID- 17450789
TI  - A chemical solution route to rapid synthesis of homogeneous Bi(100-x)Sb(x) alloys
      nanoparticles at room temperature.
AB  - A chemical co-reduction route in aqueous solution was developed to synthesize
      Bi(100-x)Sb(x) alloys at room temperature. The hydrolyses of Bi(III) and Sb(III)
      were effectively avoided by selecting proper raw materials and coordinator. X-ray
      diffraction analysis indicated that the as-prepared Bi(100-x)Sb(x) alloys were
      homogeneous and phase-pure, and the Bi/Sb ratios in the alloys were very close to
      those in the aqueous solutions. The transmission electron microscope observation
      showed that the as-prepared Bi(100-x)Sb(x) (x = 0-100) alloys were particles with
      a size of tens of nanometers. The selected area electron diffraction patterns
      confirmed the high crystallinity, the homogeneousness, and the composition
      controllability of as-prepared alloys. All these characters and the nanometer
      scaled size of the alloys are believed to be beneficial to the thermoelectric
      property of the Bi(100-x)(x)Sb(x) alloys.

PMID- 17450790
TI  - Boron nitride nanotubes: nanoparticles functionalization and junction
      fabrication.
AB  - Adopting a wet chemistry method, Au and Fe3O4 nanoparticles were functionalized
      on boron nitride nanotubes (BNNTs) successfully for the first time. X-ray
      diffraction pattern and transmission electron microscopy were used to
      characterize the resultant products. Subsequently, a method was proposed to
      fabricate heterojunction structures based on the particle-functionalized BNNTs.
      As a demonstration, BNNT-carbon nanostructure, BNNT-ZnO and BNNT-Ga2O3 junctions
      were successfully fabricated using the functionalized particles as catalysts.

PMID- 17450791
TI  - Adsorption of avermectin on porous hollow silica nanoparticles by supercritical
      technology.
AB  - Porous hollow silica nanoparticles with O.D. of approximately 100 nm and a wall
      thickness of approximately 10 nm were prepared by using inorganic CaCO3
      templates. The produced PHSN were employed as a novel carrier to study the
      adsorption of avermectin in supercritical carbon dioxide by applying different
      adsorption pressure, adsorption temperature, adsorption time and volume of
      cosolvent. The results indicated that while increasing adsorption pressure and
      time always showed a positive effect on the avermectin adsorption until
      adsorption saturation is reached, both the adsorption temperature and volume of
      cosolvent require an optimal value for achieving the maximum adsorption. It was
      found that the optimal adsorption could be obtained at an adsorption pressure of
      15 MPa and an adsorption temperature of 313 K for 90 minutes with 5 ml cosolvent.
      In addition, the desorption behavior of avermectin from the avermectin-loaded
      PHSN samples showed a sustained style: approximately 60% of avermectin was
      released in the first 20 minutes, while the other 40% followed a typical
      sustained desorption pattern and was dissolved out slowly for a time period of
      3000 minutes, which is different from the quick and complete desorption from
      solid SiO2 carriers.

PMID- 17450792
TI  - Spherical SiO2 @ GdPO4: Eu3+ core-shell phosphors: sol-gel synthesis and
      characterization.
AB  - Nanocrystalline GdPO4 : Eu3+ phosphor layers were coated on non-aggregated,
      monodisperse and spherical SiO2 particles by Pechini sol-gel method, resulting in
      the formation of core-shell structured SiO2 @ GdPO4 : Eu3+ particles. X-ray
      diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), field
      emission scanning electron microscopy (FESEM), transmission electron microscopy
      (TEM), photoluminescence (PL), low-voltage cathodoluminescence (CL), time
      resolved PL spectra and lifetimes were used to characterize the core-shell
      structured materials. Both XRD and FT-IR results indicate that GdPO4 layers have
      been successfully coated on the SiO2 particles, which can be further verified by
      the images of FESEM and TEM. Under UV light excitation, the SiO2 @ GdPO4 : Eu3+
      phosphors show orange-red luminescence with Eu3+ 5D0-7F1 (593 nm) as the most
      prominent group. The PL excitation and emission spectra suggest that an energy
      transfer occurs from Gd3+ to Eu3+ in SiO2 @ GdPO4 : Eu3+ phosphors. The obtained
      core-shell phosphors have potential applications in FED and PDP devices.

PMID- 17450793
TI  - Electromagnetic interference shielding characteristics of carbon nanofiber
      polymer composites.
AB  - Electromagnetic interference (EMI) shielding characteristics of carbon nanofiber
      polystyrene composites were investigated in the frequency range of 12.4-18 GHz
      (Ku-band). It was observed that the shielding effectiveness of such composites
      was frequency independent, and increased with increasing carbon nanofiber loading
      within Ku-band. The experimental data exhibited that the shielding effectiveness
      of the polymer composite containing 20 wt% carbon nanofibers could reach more
      than 36 dB in the measured frequency region, indicating such composites can be
      applied to the potential EMI shielding materials. In addition, the results showed
      that the contribution of reflection to the EMI shielding effectiveness was much
      larger than that of absorption, implying the primary EMI shielding mechanism of
      such composites was reflection of electromagnetic radiation within Ku-band.

PMID- 17450794
TI  - Dye-sensitized solar cells based on nanocrystalline titania electrodes made at
      various sintering temperatures.
AB  - Dye-sensitized solar cells were made by using nanocrystalline titania deposited
      on Fluorine-doped SnO2 (FTO) electrodes. Nanocrystalline titania deposition was
      made by the sol-gel method using reverse micelles of bis(2-ethylhexyl)
      sulfosuccinate sodium salt (AOT) in cyclohexane as reaction medium. This
      surfactant could be easily removed from the deposited nanocomposite organic
      inorganic film by simple rinsing with distilled water, without affecting titania
      adherence on FTO electrode. These nanocrystalline titania electrodes were used to
      make solar cells either without sintering or after sintering at various
      temperatures. Sintering extensively affected short circuit current but had small
      effect on device open-circuit voltage. Thus satisfactory photovoltaic response
      could be obtained even with devices made of non-sintered (room-temperature)
      titania.

PMID- 17450795
TI  - Enhanced electrochemical detection of DNA hybridization with carbon nanotube
      modified paste electrode.
AB  - A novel electrochemical genesensor using twice hybridization enhancement of gold
      nanoparticles based on carbon paste modified electrode is described. The carbon
      nanotube modified carbon paste electrode (CNTPE) and mesoporous molecular sieve
      SBA-15 modified carbon paste electrode (MSCPE) were investigated. The assay
      relies on the immobilization of streptavidin-biotin labeled target
      oligonucleotides onto the electrode surface and its hybridization to the gold
      nanoparticle-labeled DNA probe. After twice hybridization enhanced connection of
      gold nanoparticles to the hybridized system, the differential pulse voltammetry
      (DPV) signal of total gold nanoparticles was monitored. It was found that the
      adsorption of oligonucleotide and hybridized DPV signal on CNTPE were both
      enhanced in comparison with that of pure carbon paste electrode (CPE). But this
      trend was reverse on MSCPE. The DPV detection of twice hybridized gold
      nanoparticles indicated that the sensitivity of the genesensor enhanced about one
      order of magnitude compared with one-layer hybridization. One-base mismatched DNA
      and complementary DNA could be distinguished clearly. However, no distinct
      advantage of MSCPE over CPE was found.

PMID- 17450796
TI  - Nanostructures of bismuth sulphide: synthesis and electrical properties.
AB  - Bismuth ammonium citrate complex (C24H20Bi4O28 x 6NH3 x 10H2O) interacted with
      sodium sulphide (Na2S) in presence of beta-cyclodextrin (beta-CD) yielding Bi2S3
      nanospheres. Solvothermal treatment of the bismuth complex and dimethyl
      sulphoxide (DMSO) produced Bi2S3 nanorods. Reaction conditions were optimized to
      investigate the morphology evolution of the product. Electrical properties of the
      nanorods were monitored in details.

PMID- 17450797
TI  - Synthesis of carbon-nitrogen nanostructures by hot isostatic pressure apparatus
      and their field emission properties.
AB  - Carbon-nitrogen (CN) nanofibers were synthesized in argon-nitrogen gas mixture at
      75 MPa by high isostatic pressure (HIP) apparatus using a graphite resistive
      heater. The CN nanofibers were grown in random with the diameter of about 200 nm
      and the length over 5 microm. The structures obtained can be divided bamboo-like,
      spring-like, and bead necklace-like CN nanofibers. The nitrogen content of up to
      8.4% was found in CN nanofibers by EELS analysis. Field emission results showed
      that the density of field emitters and the field enhancement factors changed by
      surface treatments and that CN nanofibers contained glass frit. The screen
      printed CN nanofiber had a turn-on field of 2 V/microm.

PMID- 17450798
TI  - Synthesis of nanocrystalline (Co, Ni)Al2O4 spinel powder by mechanical milling of
      quasicrystalline materials.
AB  - In the present study, attempts have been made to synthesize the nano-crystalline
      (Co, Ni)Al2O4 spinel powders by ball milling and subsequent annealing. An alloy
      of Al70Co15Ni15, exhibiting the formation of a complex intermetallic compound
      known as decagonal quasicrystal is selected as the starting material for
      mechanical milling. It is interesting to note that this alloy is close to the
      stoichiometry of aluminum and transition metal atoms required to form the
      aluminate spinel. The milling was carried out in an attritor mill at 400 rpm for
      40 hours with ball to powder ratio of 20 : 1 in hexane medium. Subsequent to this
      annealing was performed in an air ambience for 10, 20, and 40 h at 600 degrees C
      in side the furnace in order to oxidize the decagonal phase and finally to form
      the spinel structure. The X-ray diffraction (XRD) and transmission electron
      microscopy (TEM) confirmed the formation of nano-sized decagonal phase after
      milling and then (Co, Ni)Al2O4 spinel type phase after annealing. The XRD studies
      reveal the lattice parameter to be 8.075 angstroms and the lattice strain as
      0.6%. The XRD and TEM explorations of spinel phase indicate the average grain
      size to be approximately 40 nm.

PMID- 17450799
TI  - A simple route to ultra long SiC nanowires.
AB  - SiC nanowires are prepared by pyrolysis of hexamethyldisilane (HMDS), at 1200
      degrees C in a flowing Ar atmosphere. The length of the nanowires is in
      millimeter scale. Transmission electron microscopy observations indicate that the
      diameters of the SiC nanowires are in the range of about 8 to 120 nm, and that
      most of the nanowires have numerous stacking faults. The formation mechanism of
      the nanowires is proposed.

PMID- 17450800
TI  - Analysis of stress responsive genes induced by single-walled carbon nanotubes in
      BJ Foreskin cells.
AB  - Nanotechnology is finding its use as a potential technology in consumer products,
      defense, electronics, and medical applications by exploiting the properties of
      nanomaterials. Single-walled carbon nanotubes are novel forms of these
      nanomaterials with potential for large applications. However, the toxicity
      studies on this material are not explored in detail and therefore limiting its
      use. It has been earlier reported that single-walled carbon nanotubes induces
      oxidative stress and also dictates activation of specific signaling pathway in
      keratinocytes. The present study explores the effect of single-walled carbon
      nanotubes on stress genes in human BJ Foreskin cells. The results show induction
      of oxidative stress in BJ Foreskin cells by single-walled carbon nanotubes and
      increase in stress responsive genes. The genes included inducible genes like
      HMOX1, HMOX2, and Cyp1B1. In addition we validated increase for four genes by
      SWCNT, namely ATM, CCNC, DNAJB4, and GADD45A by RT-PCR. Moreover results of the
      altered stress related genes have been discussed and that partially explains some
      of the toxic responses induced by single-walled carbon nanotubes.

PMID- 17450801
TI  - Structure and photoluminescent properties of microstructural YBO3 : Eu3+
      nanocrystals.
AB  - YBO3 : Eu3+ nanocrystals (NCs) were prepared by a hydrothermal method and
      characterized by field emission scanning electron microscopy (FE-SEM),
      transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier
      transform infrared (FTIR) spectroscopy. The results demonstrate that morphology
      and structure of the NCs varied strongly with hydrothermal temperature. Their
      luminescent properties were investigated in comparison to the bulk. A large
      number of NO3- groups were adsorbed at the surface of hydrothermal products,
      which acted as luminescent killers; Two symmetry sites of Eu3+ ions in NCs, the
      interior and the surface sites, were identified by the site-selective excitation
      and time-resolved emission experiments; The intensity ratio of 5D0-7F2 to 5D0-7F,
      of EU3+ at the surface site increased greatly than that at the interior site; as
      a result, the chromaticity was improved; The total radiative transition rate of
      5D0-sigmaJ7FJ for Eu3+ at the surface site was 3-5 times larger than that at the
      interior.

PMID- 17450802
TI  - Nanostructured CaWO4, CaWO4 : Pb2+ and CaWO4 : Tb3+ particles: polyol-mediated
      synthesis and luminescent properties.
AB  - Nano-submicrostructured CaWO4, CaWO4 : Pb2+ and CaWO4 : Tb3+ particles were
      prepared by polyol method and characterized by X-ray diffraction (XRD), field
      emission scanning electron microscopy (FE-SEM), transmission electron microscopy
      (TEM), Fourier transform infrared spectra (FT-IR), thermogravimetry-differential
      thermal analysis (TG-DTA), photoluminescence (PL), cathodo-luminescence (CL)
      spectra and PL lifetimes. The results of XRD indicate that the as-prepared
      samples are well crystallized with the scheelite structure of CaWO4. The FE-SEM
      images illustrate that CaWO4 and CaWO4 : Pb2+ and CaWO4 : Tb3+ powders are
      composed of spherical particles with sizes around 260, 290, and 190 nm
      respectively, which are the aggregates of smaller nanoparticles around 10-20 nm.
      Under the UV light or electron beam excitation, the CaWO4 powders exhibits a blue
      emission band with a maximum at about 440 nm. When the CaWO4 particles are doped
      with Pb2+, the intensity of luminescence is enhanced to some extent and the
      luminescence band maximum is red shifted to 460 nm. Tb(3+)-doped CaWO4 particles
      show the characteristic emission of Tb3+ 5D4-7FJ (J = 6 - 3) transitions due to
      an energy transfer from WO4(2-) groups to Tb3+.

PMID- 17450803
TI  - On the effect of nanocrystallization and disorder on the magnetic properties of
      Cu-rich, FeMnCu alloys.
AB  - We report on the temperature dependencies of the Mossbauer spectra and the AC
      magnetic susceptibility measured in Cu-rich, FeMnCu samples prepared by
      mechanically alloying, using, on the one side, Cu and prealloyed FeMn powders
      and, on the other, pure element Cu, Mn, and Fe powders. From the correlation of
      the Mossbauer and susceptibility data we conclude about the basic characteristics
      of the phase distributions present in the different studied samples. Those
      distributions are a consequence of both the nanostructure induced upon milling
      and of the different signs of the Mn/Cu (negative) and Fe/Cu (positive)
      enthalpies of mixing. The proposed phase distributions are significantly
      different in the samples prepared from different precursors and this fact is
      analyzed in terms of the disproportion of the precursor FeMn alloy and in those
      of the favoured Mn/Cu interdiffusion and the hindered Fe/Cu one.

PMID- 17450804
TI  - Growth aspects of photochemically synthesized silver triangular nanoplates.
AB  - Aspects of the growth mechanism of silver triangular nanoplates by photochemical
      synthesis were addressed by detailed characterization using ultraviolet-visible
      spectroscopy, electron microscopies, and atomic force microscopy. The
      quantitative characterization of their size and thickness during the reaction
      showed that both increase with time as well as the aspect ratio. Samples
      irradiated by different wavelengths showed that the size of the nanoplates can be
      controlled by the incident wavelength and it is responsible for the increase of
      the aspect ratio, but the thickness seems to be determined by the conditions of
      the initial seeds. It was also found that irradiation with wavelength out of
      resonance with the surface plasmon of the initial seeds leads to a slower
      kinetics. The results suggested that rational exploration of the synthesis
      parameter such as the type of the initial seeds in combination with the
      wavelength irradiation may lead to a broader type of particles already obtained
      by this method.

PMID- 17450805
TI  - Preparation of poly(MAA-g-EG) hydrogel nanoparticles by a thermally-initiated
      free radical dispersion polymerization.
AB  - Poly(methacrylic acid-grafted-poly(ethylene glycol)) (P(MAA-g-EG)) hydrogel
      nanoparticles (HNPs) were prepared by a thermally-initiated free radical
      dispersion polymerization method. The effects of various reaction parameters on
      the preparation of HNPs were investigated, including the quantity of monomer,
      temperature, initiator dosage, crosslinker dosage, and co-stabilizer
      concentration. The reaction temperature at 75 degrees C was found to be suitable
      for preparing stable and small P(MAA-g-EG) HNPs. By adding a little amount of
      polyvinyl alcohol in the reaction media, P(MAA-g-EG) HNPs with narrow size
      distribution could be obtained. The effects of pH and the crosslinker dosage on
      the equilibrium swelling behavior of P(MAA-g-EG) HNPs were also studied. The
      P(MAA-g-EG) HNPs perform pH-responsive swelling behavior, which is strongly
      influenced by the crosslinker dosage.

PMID- 17450806
TI  - Millable polyurethane/organoclay nanocomposites: preparation, characterization,
      and properties.
AB  - Novel millable polyurethane (PU)/organoclay nanocomposites have been successfully
      prepared by conventional transformation techniques. One natural (C6A) and two
      organically modified (C15A and C30B) montmorillonites have been used as clays for
      preparing PU nanocomposites. The optimum dispersion of nanofiller at a nanometer
      scale in PU matrix was confirmed by X-ray diffraction patterns and transmission
      electron microscopy. A substantial improvement of the PU properties by addition
      of only a small amount of organoclay was observed. It is worthy to note that the
      organoclays show a different interfacial interaction with the PU matrix, which
      was reflected in different macroscopic properties. Thus, C30B organoclay seems to
      react with PU chains to form covalent bonds, while C15A only interacts physically
      with PU chains. Mechanical and barrier properties are analyzed.

PMID- 17450807
TI  - Sputter deposition of self-organized nanoclusters through porous anodic alumina
      templates.
AB  - Silver nanoparticles were sputter deposited through self organized hexagonally
      ordered porous anodic alumina templates that were fabricated using a two-step
      anodization process. The average pore diameter of the template was 90 nm and the
      interpore spacing was 120 nm. Atomic force microscope studies of the sputter
      deposited silver nanoparticle array on a Si substrate indicate an approximate
      replication of the porous anodic alumina mask. The nature of the deposition
      depends strongly on the process parameters such as sputtering voltage, ambient
      pressure and substrate temperature. We report a detailed study of the sputtering
      conditions that lead to an optimal deposition through the template.

PMID- 17450808
TI  - Synthesis of silicon carbide nanotubes by chemical vapor deposition.
AB  - Silicon carbide nanotubes (SiCNTs) were directly synthesized by chemical vapor
      deposition (CVD) in the paper. Methyltrichlorosilane (MTS) was selected as the
      SiC gaseous source and, ferrocence and thiophene as the catalyst and the
      cocatalyst, respectively. The influences of reaction temperature, contents of
      catalyst and cocatalyst, and content of gaseous source on the morphologies of the
      products were investigated, respectively. The products were identified by high
      resolution transmission electron microscopy (HRTEM), scanning electron microscopy
      (SEM), X-ray diffraction (XRD), and energy-dispersive X-ray (EDX), respectively.
      The synthesis of SiCNTs by CVD suggested a condition-dependent process. Novel
      SiCNTs, with 20 approximately 80 nm in outer diameter and 15 approximately 35 nm
      in inner diameter, respectively, were observed. The wall structure similar to
      that of carbon nanotubes was not found for the SiCNTs.

PMID- 17450809
TI  - Influence of surface electrode on luminescent properties of nanocrystalline
      silicon electroluminescent device.
AB  - We describe the electrical and luminescence properties of nanocrystalline silicon
      (nc-Si) based red electroluminescent (EL) devices using an indium tin oxide (ITO)
      and/or gold (Au) films as a surface electrode, and the variation in the
      transmittance and resistivity of two electrodes with various film thicknesses.
      The increase in the film thickness from 50 to 200 nm of the ITO electrode led to
      the lowering of resistivity from 2.0 x 10(-3) to 9.1 x 10(-4) omega cm and almost
      the same value (83-92%) of transmittance in the red region. On the other hand,
      the Au electrode was lowered the resistivity from 1.8 x 10(-4) to 1.6 x 10(-5)
      omega cm and the transmittance in the red region from 42 to 1.8% with increasing
      the film thickness from 10 to 80 nm. Moreover, the red luminescence from the EL
      devices using the ITO and/or Au electrodes having thickness of 200 and 10 nm,
      respectively, obtained by applying the direct current forward voltage above 4.5
      and 2.5 V and/or by flowing the forward current density above 53 and 38 mA/cm2,
      respectively. However, the luminescence intensity of EL device with the ITO
      electrode strengthened more than about one order of magnitude in comparison to
      that of the EL device with the Au electrode. This was due to the high value of
      transmittance in the red region of the ITO electrode. We suggest that the ITO
      electrode is an optimum surface electrode for the realization of nc-Si based EL
      device with the high brightness.

PMID- 17450810
TI  - Nanoindentation studies on amorphous, nanoquasicrystalline and nanocrystalline
      Zr8oPt2o and Zr75Pd25 alloys.
AB  - Nanoindentation studies on rapidly solidified Zr80Pt20 and Zr75Pd25 binary alloys
      with nanocrystalline, nanoquasicrystalline, and amorphous microstructures are
      reported. The results indicate that the hardness and elastic modulus are the
      highest for a mixture of amorphous and nanoquasicrystalline state among the
      various microstructures studied. Nanoquasicrystalline phase has high hardness and
      elastic modulus in comparison to amorphous and nanocrystalline phases. The
      hardness to modulus ratio is close to 0.1 in both the alloys, irrespective of the
      phase/phase mixture studied indicating that the bonding in these alloys is of
      covalent nature. In Zr80Pt20, all the phases/phase mixtures have higher hardness
      and modulus in comparison to similar microstructures in Zr75Pd25 due to higher
      bond energies caused by more negative heat of mixing in the former case.

PMID- 17450811
TI  - Synthesis and characterization of nanodispersed molecular aggregates of Prussian
      blue in aerosol OT reverse micelle.
AB  - Prussian Blue (PB) nanomolecular aggregates were prepared in a well
      characterized, monodispersed biomimicking nanocavities formed by Aerosol OT (AOT)
      reverse micelle in H2O/AOT/heptane at different omega ([H2O]/[Surfactant])
      employing coprecipitation technique. The formed nanomolecular aggregates of PB
      have been characterized by the UV-visible, Fourier Transformed Infrared (FTIR)
      spectroscopy as well as by Transmission Electron Microscopy (TEM) and Cyclic
      Voltammetric methods. Visible and FTIR spectroscopic measurements confirm the
      formation of PB nano aggregates. Experimental results reveal that the molar
      extinction coefficient of PB nanomolecular aggregates is different for two
      different regimes of omega of reverse micelles. TEM measurements show that the
      size of these reverse micellar entrapped nano aggregrates varied with hydration
      (omega). Studies on these nano sized particles indicate that Fe is present in a
      single mixed valence state along the Fe-C-N-Fe skeleton in PB and the half wave
      potential (E1/2) becomes more positive with increase in the size of the nano
      aggregates.

PMID- 17450812
TI  - Synthesis of TiO2-based nanotube on Ti substrate by hydrothermal treatment.
AB  - TiO2-based titanate nanotube film was directly synthesized by hydrothermal
      treatment of Ti substrate in NaOH solution. The prepared high aspect ratio
      nanotubes have diameter of 10 nm and pore size of 5 nm with length of several
      microns. The nanotubes show the same structure and component characteristics as
      the nanotubes prepared through hydrothermal treatment of TiO2. Other
      nanostructured titanate as oriented nanofiber film and translucent film were also
      prepared by adjusting the hydrothermal conditions. The formation mechanism of
      nanostructured titanate was discussed.

PMID- 17450813
TI  - A template-based electrochemical method for the synthesis of high dense nickel
      nanotube arrays.
AB  - High dense Ni nanotube arrays have been successfully fabricated using
      electrochemical method with the assistance of anodic aluminum oxide (AAO)
      template from NiSO4 aqueous solution without any additive. Field emission
      scanning electron microscope (FE-SEM) results indicate that the pores of AAO
      template are high uniform and all the pores are filled with Ni nanotubes.
      Transmission electron microscope (TEM) results demonstrate that the diameter of
      Ni nanotubes is about 65 nm. The electron diffraction (ED) pattern results show
      that the Ni nanotubes are polycrystalline. X-ray diffraction (XRD) pattern shows
      that the electrodeposited nickel is hexagonal crystal structure.

PMID- 17450814
TI  - Solvothermal synthesis of CdS nanorods: role of basic experimental parameters.
AB  - CdS nanorods with varying dimensions were synthesized by solvothermal process. It
      was observed that the anions present with the Cd-salts play an important role in
      determining the dimensions of the CdS nanorods. The crystalline nature of the
      sources was found to play a crucial role in determining the phase of the
      products. The nature of the sulfur source, molar ratio of the precursors, filling
      fraction of the solvent, and the synthesis temperature play important role in
      defining the size and shape of the products. By controlling the experimental
      parameters it was possible to control the dimension of the CdS nanorods within a
      certain range (diameter of the nanorods could be varied within a wide range from
      approximately 7 to 100 nm by varying the temperature within 100-250 degrees C).
      Optical absorption, photoluminescence, and Raman studies of these samples were
      carried out to characterize the CdS nanorods.

PMID- 17450815
TI  - Multipod znO nanoforms: low temperature synthesis and characterization.
AB  - ZnO nanotetrapods were synthesized by a simple thermal evaporation of Zn powder
      at a relatively low temperature approximately 600 degrees C. The tetrapods have
      four legs with hexagonal cross-section. Interpenetrating growth was observed in
      some of these nanotetrapods. Multipod ZnO nanoforms were produced at higher
      temperature. The optical characterizations such as optical absorbance,
      photoluminescence and Raman spectroscopy reveal excellent crystal qualities of
      these nanoforms. The field emission studies indicated that these nanoforms could
      be utilized in field emission based devices.

PMID- 17450816
TI  - Catalyst-free template-synthesis of ZnO nanopetals at 60 degrees C.
AB  - We report successful growth of a new form of ZnO nanostructures, ZnO nanopetals
      at low temperature. This two-dimensional nanostructure is morphologically
      different from nanowalls. The flat and circularly edged nanopetals intersect each
      other. The thickness of nanopetals is uniform and about 30 nm. The nanostructure
      was produced using a simple catalyst-free chemical method based on anodic
      aluminum oxide (AAO) template. The growth temperature was 60 degrees C which is
      much lower than that required for growing ZnO nanowalls. The formation of the
      nanopetal network was induced by the porous alumina network on the surface of the
      AAO template.

PMID- 17450817
TI  - Doped ZnO nanowires obtained by thermal annealing.
AB  - Doped ZnO nanowires were prepared in a very simple and inexpensive thermal
      annealing method using ZnSe nanowires as a precursor. As doped, P doped, and As/P
      codoped ZnO nanowires were obtained in this method. X-ray diffraction shows that
      the zincblende ZnSe nanowires were converted to doped wurtzite ZnO nanowires. The
      incorporation of the dopants was confirmed by energy dispersive X-ray
      spectroscopy. The doping concentration could be adjusted by changing the
      annealing temperature and duration. Scanning electron microscopy indicated that
      the morphology of the ZnSe nanowires was essentially retained after the annealing
      and doping process. Photoluminescence spectroscopy also verified the
      incorporation of the dopants into the nanowires.

PMID- 17450818
TI  - Pattern formation in nanoporous titania templates.
AB  - We have carried out a systematic investigation into the formation of nanoscaled
      patterns in titania (TiO2) templates under dc anodization of Ti in HF acid. At
      lower acid concentrations (around 0.5 wt% HF) either pores or tubes form at the
      surface of anodized titanium foil. The pores or nanotubes are separated from the
      bottom Ti layer by a thin barrier layer of TiO2. The critical voltage where the
      transition from pores to tubes occurs has been determined. It is observed that
      the transition voltage shift towards higher voltages as acid concentration is
      increased, with pore formation disappearing altogether at high acid
      concentrations. We have also carried out a systematic investigation into the
      dependence of pore and tube parameters on the applied dc anodization voltage. Our
      results indicate that the barrier layer thickness, pore and tube length increase
      as a function of applied voltage.

PMID- 17450819
TI  - Sunlight-driving formation and characterization of size-controlled gold
      nanoparticles.
AB  - Exposing a sodium citrate-HAuCl4 aqueous solution to sunlight results in the
      formation of size-controlled, citrate-capped gold nanoparticles. The gold
      nanoparticles were characterized by UV-visible, transmission electron microscopy
      (TEM), scanning electron microcopy (SEM), and X-ray diffraction (XRD)
      spectroscopic methods. It provides a general methodology for the economic,
      convenient, mild preparation of citrate-capped noble metal nanoparticles.

PMID- 17450820
TI  - Fast colorimetric detection of copper ions using L-cysteine functionalized gold
      nanoparticles.
AB  - This communication reports an efficient visual detection method of Cu2+ by L
      cysteine functionalized gold nanoparticles in aqueous solution. Upon exposure to
      Cu2+, the gold nanoparticle solution changed from red to blue, in response to
      surface plasmon absorption of dispersed and aggregated nanoparticles. This
      colorimetric sensor allows a rapid quantitative assay of Cu2+ down to the
      concentration range of 10(-5) M. Recognition of Cu2+ and formation of the
      aggregates are proposed to occur via a 2 : 1 sandwich complex between L-cysteine
      and Cu2+.

PMID- 17450821
TI  - Diffusion in Si(x)Ge(1-x)/Si nanowire heterostructures.
AB  - Si0.48Ge0.52/Si tip/nanowire heterostructures were grown by pulsed laser
      vaporization (PLV) at a growth temperature of 1100 degrees C. Ge diffusion in
      [111]-growth Si nanowires was studied for different post-synthesis annealing
      temperatures from 200 degrees C to 800 degrees C. Ge composition profiles were
      quantified by energy-dispersive X-ray spectroscopy in a transmission electron
      microscope. The compositional profiles were modeled by a limited-source diffusion
      model to extract temperature-dependent diffusion coefficients. The Ge diffusion
      coefficients followed an Arrhenius relationship with an activation energy of
      0.622 +/- 0.050 eV. This rather low activation energy barrier is similar to the
      previously reported activation energy barrier of 0.67 eV for Ge surface diffusion
      on Si, suggesting that surface diffusion may dominate in nanowires at this length
      scale.

PMID- 17450822
TI  - In-vitro reconstitution of hepatic tissue architectures with neonatal mouse liver
      cells using three-dimensional culture.
AB  - Stem cells have the potential to differentiate into multiple lineages, and the
      capabilities to self-renew, and reconstitute tissues following transplantation.
      Thus, stem cells are expected to be useful for regenerative medicine; however,
      the mechanisms that regulate the reconstitution of three-dimensional (3-D)
      tissues remain to be elucidated. To study such mechanisms, we have established a
      novel procedure of 3-D culture that supports the formation of tissues from
      isolated cells, including hepatic stem/progenitor cells in vitro. We cultured
      neonatal mouse liver cell populations, including hepatic stem/progenitor cells,
      in a simulated microgravity environment produced by a Rotating Wall Vessel
      bioreactor. After 8 days in culture, we obtained a 3-D tissue architecture.
      Histological analysis showed that bile duct structures secreting mucin formed
      complicated tubular branches in the peripheral region. In the non-bile duct
      structure region, we observed mature hepatocytes that were capable of producing
      albumin and storing glycogen. Thus, we were able to establish a novel 3-D culture
      system that is able to reconstitute functional hepatic tissue architecture from
      isolated neonatal mouse liver cells.

PMID- 17450823
TI  - DNA microstructure based on self-assembly of 4-sticky-end Holliday junctions in
      aqueous solution.
AB  - Liverwort-like DNA microscale structures consist of 4-sticky-end Holiday
      junctions as DNA bricks that can be used in nanotechnology and nanobiotechnology
      to direct the self-assembly of nanomachines as well as DNA assembly. Previously
      it has not been possible to obtain such DNA microscale structural forms, but
      herein we report construction of a mesh-like material made up of 4 strands of 40
      base DNA. Advanced bioimaging techniques such as fluorescence correlation
      spectroscopy (FCS), laser scanning microscopy (LSM), and atomic force microscopy
      (AFM) help us as ultrasensitive detection tools for examing structures in
      solutions. Combinations of these techniques allow us to survey various chemical
      conditions of materials and solutions.

PMID- 17450824
TI  - Regeneration of peripheral nerves by bioabsorbable polymer tubes with fibrin gel.
AB  - We developed two types of nerve conduits, straight tubes, and bellows tubes, for
      peripheral nerve regeneration with bioabsorbable polymer membranes. Mechanical
      properties of these straight and bellows tubes were analyzed. 30 straight tubes
      and 30 bellows tubes were implanted to a nerve defect made in a rat sciatic nerve
      and the nerve regeneration in the tube was investigated. A half of these tubes
      were utilized alone and the others were filled with fibrin gel made from
      coagulated plasma and implanted. Bellows tubes were superior in mechanical
      characteristics to straight tubes and the inner cavities of the bellows tubes
      were suitably maintained after implantation. At 4 weeks after operations,
      remyelinations were observed in the regenerated tissue at the location of the
      middle parts of the tubes filled with fibrin gel whereas no remyelinations in the
      tubes without fibrin gel. The use of fibrin gel as filling materials within the
      tubes significantly enhanced the nerve regeneration. The fibrin gel might be soft
      nanomaterials significantly enhance the regeneration of the peripheral nerves. We
      concluded that the developed bioabsorbable bellows tubes filled with fibrin gel
      were effective for peripheral nerve regeneration.

PMID- 17450825
TI  - Application of oligonucleotide as a template for the assembly of nucleoamphiphile
      bearing azobenzene at the air-water interface.
AB  - In order to assemble amphiphilic adenine having azobenzene, C12AzoC5Ade (AzoAde),
      at the air-water interface based on the molecular recognition of DNA, we prepared
      aqueous linear oligothymidylic acids, dTn (n = 4, 6, 8, 10, 30), subphase as
      templates. Surface pressure-area (pi-A) isotherms and UV-Vis reflection
      absorption spectra of AzoAde were measured to investigate the effect of chain
      length of the oligothymidylic acid on the molecular recognition by forming a
      complementary A-T base pair. It was showed that AzoAde did not form a stable
      monolayer on the dT4 subphase and remained monomeric state. While AzoAde provided
      expanded monolayers and formed J-aggregates of azobenzene moieties on the dTn (n
      > 4) subphases even at the low molecular density. We also investigated the
      molecular recognition of template oligonucleotides by comparing dT30 with dA30,
      indicating that AzoAde had not a specific interaction with dA30 at the air-water
      interface due to base mismatching. The AzoAde monolayer on the dA30 subphase gave
      H-aggregate from monomeric state by compressing it. On the other hand, it
      remained J-aggregated state on dT30 subphase regardless of compression. It was,
      therefore, suggested that the linear oligothymidylic acids, dT, (n > 4), acted as
      templates for assembling AzoAde at the air-water interface.

PMID- 17450826
TI  - Material design of bioabsorbable inorganic/organic composites for bone
      regeneration.
AB  - Two new bioabsorbable inorganic/organic composite materials were developed for
      bone regeneration. One material used was beta-TCP/PLGC in which poly(L-lactide-co
      glycolide-co-epsilon-caprolactone) and beta-tricalcium phosphate were used as the
      matrix and filler, respectively. The other material used was HAp/Col-a soft
      nanocomposite of hydroxyapatite and type I collagen. Using these composites, two
      bone implants were designed. The efficacy of these implants was investigated by
      applying them to the critical-sized bone defects that were created in the canine
      tibia. Although no tissue engineering techniques such as application of growth
      factors or stem cells was utilized, successful healing was observed. These
      results suggested that bone regeneration in the critical-sized defects is
      possible without the use of growth factors or stem cells if the materials and the
      bone implants are suitably designed.

PMID- 17450827
TI  - Development of a novel glue consisting of naturally-derived biomolecules: citric
      acid and human serum albumin.
AB  - A novel glue consisting of human serum albumin (HSA) and citric acid derivative
      (CAD) was developed where the glue is named as CAD-A glue. In this adhesive, CAD
      works as a crosslinking reagent of HSA. For preparing crosslinking reagent CAD,
      using citric acid as a starting material, three carboxyl groups of a citric acid
      were modified with N-hydroxysuccinimide in the presence of 1-ethyl-3-(3-dimethyl
      aminopropyl) carbodiimide hydrochloride. From 1H-NMR spectrum, CAD with three
      active ester groups in a molecule was successfully synthesized with a high yield
      (more than 80%). The boding time of CAD-A glue to collagen-based casing was
      saturated within 15 minutes. The bonding strength of this glue to collagen-based
      casings increased with increasing of HSA concentration. The maximum bonding
      strength of CAD-A glue was a slightly low level compared to the bonding strength
      of cyanoacrylate adhesive and was 9 times higher than that of fibrin glue. The
      CAD-A glue showed excellent biocompatibility and high ability of wound closure
      similar to that of cyanoacrylate-based adhesive when glues were applied to the
      mouse skin. These results suggested that this developed adhesive had both tissue
      compatibility and bonding strength for use in clinical field.

PMID- 17450828
TI  - An attempt to construct the stroma of cornea using primary cultured corneal
      cells.
AB  - The number of patients currently awaiting corneal transplantation has resulted in
      the need to develop an artificial corneal replacement. In this study, we aimed to
      construct the corneal stroma using non-transformed corneal cells and a perfusion
      cell culture method. Corneal cells isolated from chicken embryos or rabbit and
      were embedded in the alkaline solubilized collagen gels crosslinked by TSG
      (Pentaerythritol polyethyleneglycol ether tetrasuccinimidyl glutarate). During
      culture, the majority of cells migrated from inside of the gel. The chicken and
      rabbit cells changed their morphology and stratified structures were constructed
      within the gels. These microstructures were similar to the natural corneal
      tissue. TEM analysis was performed to confirm the nano-microstructure of the
      constructs. Contrary to expectation, the cornea-like nanostructure of collagen
      fibrils was not observed within the gels. Further study including for example,
      such as the addition of dynamic stress or co-culture with endothelial cells, are
      therefore required in order to produce artificial constructs with the same
      superstructure as natural corneal tissue.

PMID- 17450829
TI  - Detection of influenza virus hemagglutinin with randomly immobilized anti
      hemagglutinin antibody on a carbon nanotube sensor.
AB  - Carbon nanotube sensors were capable of detecting hemagglutinin binding to anti
      hemagglutinin antibody immobilized on the sensor. The carbon nanotube sensors
      were fabricated by chemical vapor deposition method and it showed field effect
      transistor property. Anti-hemagglutinin antibody was immobilized by cross-linking
      on the reverse surface of the carbon nanotube sensor. The current between the
      source and the drain was measured after incubation of various concentration of
      hemagglutinin antigen with immobilized anti-hemagglutinin antibody. I-Vgate curve
      was obtained by plotting the current as a function of the potential applied to
      the back gate. The I-Vgate curve showed a positive shift in a manner dependent on
      the hemagglutinin antigen concentration after immobilization of anti
      hemagglutinin while no shift was observed without immobilization of anti
      hemagglutinin antibody on the surface. The sensitivity of the CNT sensor was
      higher than that of the QCM method even without controlling the orientation of
      the anti-hemagglutinin antibody. This method constitutes a new tool to analyze
      interactions among biomolecules on a substrate.

PMID- 17450830
TI  - Teleost fish scales: a unique biological model for the fabrication of materials
      for corneal stroma regeneration.
AB  - The corneal stroma is composed of multiple lamellae, each containing closely
      packed collagen fibrils. The orientation of fibrils in a lamella is parallel, but
      those in different lamellae are orthogonal. As a result, the corneal stroma has a
      characteristic orthogonal plywood-like structure. Such a highly-regulated three
      dimensional arrangement of collagen fibrils gives strength and transparency to
      the corneal stroma, but it also presents a challenge in the fabrication of
      materials to replace it. A bioinspired technology is required to process such
      materials, but the regulatory mechanism of collagen-fibril orientation is still
      unknown. The low regenerating activity of the corneal stroma seems to be a major
      factor preventing progress in this field of research. A similarly highly-ordered
      arrangement of collagen fibrils can be seen in the basal plates of teleost fish
      scales. Moreover, the scales have high regenerating ability. When a scale is
      mechanically lost, a new scale is rapidly regenerated. The cells that produce the
      basal plates are extremely activated; thus, production of the highly-ordered
      collagen fibrils is very rapid. Therefore, the regenerating scales should be a
      uniquely helpful biological model for studying the regulatory mechanism of
      collagen-fibril orientation. Fish-scale collagen has another advantage for use as
      a biomaterial: the low probability of zoonotic infection. Therefore, scale
      collagen is a most promising biomaterial for fabricating three-dimensionally
      arranged collagen fibers to substitute for the corneal stroma. Three tasks that
      must be clarified for the bioinspired production of a corneal substitute from
      fish scale collagen are proposed.

PMID- 17450831
TI  - Effect of pore size of self-organized honeycomb-patterned polymer films on
      spreading, focal adhesion, proliferation, and function of endothelial cells.
AB  - The design of nano- and microstructures based on self-organization is a key area
      of research in the search for new materials, and it has a variety of potential
      applications in tissue engineering scaffolds. We have reported a honeycomb
      patterned polymer film (honeycomb film) with highly regular pores that is formed
      by self-organization. This study describes the behavior of vascular endothelial
      cells (ECs) on honeycomb films with four different pore sizes (5, 9, 12, and 16
      microm) as well as on a flat film. We examined the influence of the honeycomb
      pattern and pore size on cell behavior. The changes in cell morphologies, actin
      filaments, vinculin clusters, cell proliferation, and secreted extracellular
      matrix (ECM) (fibronectin, laminin, type IV collagen, and elastin) production
      profiles were observed by using optical, fluorescence, and scanning electron
      microscopy. The ECs that adhered to the flat film showed an elongated morphology
      with random orientation; the actin filaments and focal adhesions were not
      conspicuous. On the other hand, the ECs on the honeycomb films exhibited greater
      spreading and flattening; the degree of spreading of the ECs increased with an
      increase in the pore size. The actin filaments and focal adhesions appeared
      conspicuous, and the focal adhesions localized along the edge of the honeycomb
      pores were distributed over the entire projected cell area. The honeycomb film
      with a pore size of 5 microm showed the highest cell proliferation and ECM
      production profiles. These results suggest that the honeycomb film is a suitable
      material for designing a new vascular device.

PMID- 17450832
TI  - Selective cell spreading, proliferation, and orientation on micropatterned gel
      surfaces.
AB  - Hydrogel micropatterns of 10 approximately 200 microm in width were introduced
      during the polymerization of 2-acrylamido-2-methyl-propane sulfonic acid sodium
      salt (NaAMPS) on the surface of polyacrylamide (PAAm) gel. Behaviors of
      endothelial cells on the micropatterned PNaAMPS/PAAm gel surfaces were studied.
      Cells selectively proliferate on micropatterned PNaAMPS surface but not on PAAm
      surface, which requires no modification with any cell adhesive proteins or
      peptides. We found that decrease of the width of the micropatterns could increase
      the degree of anisotropic spreading of cells and the degree of cell orientation.
      These results demonstrated that the topographical micropatterns of hydrogel could
      control cell behaviors.

PMID- 17450833
TI  - Integration of hydrogels with hard and soft microstructures.
AB  - Hydrogels, i.e., water-swollen polymer networks, have been studied and utilized
      for decades. These materials can either passively support mass transport, or can
      actively respond in their swelling properties, enabling modulation of mass and
      fluid transport, and chemomechanical actuation. Response rates increase with
      decreasing hydrogel dimension. In this paper, we present three examples where
      incorporation of hydrogels into solid microstructures permits acceleration of
      their response, and also provides novel functional capabilities. In the first
      example, a hydrogel is immobilized inside microfabricated pores within a thin
      silicon membrane. This hydrogel does not have a swelling response under the
      conditions investigated, but under proper conditions it can be utilized as a part
      of an electrolytic diode. In the second example, hydrogels are polymerized under
      microcantilever beams, and their swelling response to pH or glucose concentration
      causes variable deflection of the beam, observable under a microscope. In the
      third example, swelling and shrinking of a hydrogel embedded in a microfabricated
      valve structure leads to chemical gating of fluid motion through that valve. In
      all cases, the small size of the system enhances its response rate.

PMID- 17450834
TI  - Force spectroscopy on single polymer incorporated into polymer gels.
AB  - We conducted the extraction experiments of single polymer incorporated into
      hydrogels with an atomic force microscope (AFM) as a model for investigating
      nonspecific intermolecular interactions between macromolecules in a semidilute
      region at the single molecule level. Small amount of poly(ethylene glycol) (PEG)
      terminated with a thiol group was inserted in poly(acrylamide) gels, and a part
      of PEG polymer segments on the gel surface was attempted to pull out of the gels
      with a gold-coated AFM tip. The observed force-distance curves were classified
      into two kinds of extraction force profiles: a plateau force, which is almost
      constant irrespective of the tip-surface distance and a nonlinear force, which
      nonlinearly increases with the extraction length. Characteristic interaction
      length, L, and force, F, of these extraction force profiles were measured with
      changing the crosslinker concentration of gels which strongly affects the network
      structures. As a result, L of these extraction profiles significantly decreased
      at crosslinker concentrations higher than a standard one at which most gels have
      been prepared for investigating their physical properties. On the other hand, F
      showed no obvious difference on the change in crosslinker concentrations both on
      the plateau and the nonlinear force profiles. The origin of the observed forces
      was discussed in terms of gel network structures.

PMID- 17450835
TI  - Surface characterization of poly(N-isopropylacrylamide) grafted tissue culture
      polystyrene by electron beam irradiation, using atomic force microscopy, and X
      ray photoelectron spectroscopy.
AB  - To understand features of polymers grafted by electron beam (EB) irradiation
      method, we investigated topology of poly(N-isopropylacrylamide) (PIPAAm) grafted
      tissue culture polystyrene (TCPS) (PIPAAm-TCPS) prepared by EB irradiation, using
      atomic force microscopy (AFM) in air and under aqueous conditions. Furthermore,
      surfaces properties of PIPAAm-TCPS surfaces before and after cell culture were
      also examined for evaluation of functionality of the surface as biomaterials,
      using XPS analysis. Three types of PIPAAm-TCPSs with different graft densities
      (1.0+/-0.1, 1.6+/-0.1, and 2.0+/-0.1 microg/cm2 of the grafted) were obtained
      (abbreviated as 11PIPAAm-, 16PIPAAm-, and 20PIPAAm-TCPS) by using different
      initial monomer concentration (20, 55, and 65 wt%). Contact angles (costheta
      value) of the surfaces increased with an increase in density of the grafted
      polymer. AFM observation in air clearly revealed that original TCPS surface
      possesses scratched and grooved topology (ca. 10 nm height of the scratch), while
      PIPAAm-TCPSs surfaces exhibited nanoordered PIPAAm particle-like domains. The
      size of the particles also increased proportionally initial IPAAm monomer
      concentration. The 11PIPAAm-and 16PIPAAm-TCPS surfaces having ca. 10-30 nm and
      ca. 40-50 nm size of the particles also displayed scratched and grooved topology
      featured in basal TCPS. However, the larger sizes of the particles (ca. 40-100
      nm) formed on 20PIPAAm-TCPS surfaces adequately conceals the topological feature
      of the basal TCPS surfaces. The AFM images indicate that the graft polymer is as
      ultra thin as the scratch and grooves featured on basal TCPS are discernible, and
      the grafted PIPAAm layer become thicker with an increase of the monomer
      concentration. For 16PIPAAm-TCPS surfaces, the nanoordered particles were also
      observable in aqueous conditions at 20 degrees C and 37 degrees C. Comparison
      between the images obtained at 20 degrees C and 37 degrees C suggest that the
      domains are not likely to exhibit significant swelling and shrinking by
      temperature change, although the topology of PIPAAm grafted onto clover glass
      surface (50 microm thickness of the gel layer) were dramatically changed by
      temperature change in early reports. This difference should be due to ultra thin
      thickness of the grafted PIPAAm, which is subject to more restricted molecular
      motion by basal hydrophobic TCPS interfaces, as we reported previously. XPS C1s
      and N1s spectra of 16PIPAAm-TCPS surface after removal of cells suggest that
      proteins and/or peptides components possibly remained on the surfaces. Based on
      results from XPS analysis, we further discuss surface properties of 16PIPAAm-TCPS
      as biomaterials, comparing those of PIPAAm grafted polystyrene prepared by a
      radio frequency plasma method used in recent reports.

PMID- 17450836
TI  - Micro- and nano-patterned substrates to manipulate cell adhesion.
AB  - Cell adhesion to material surfaces regulates host responses to implanted
      biomaterials and the performance of cell arrays and biotechnological cell culture
      supports. Therefore, the engineering of substrates that control cell adhesive
      interactions is critical to the development of bio-interactive interfaces and
      biotechnological culture supports. We describe the application of advanced
      fabrication techniques to engineer substrates with well defined chemistry and
      topography to manipulate cell adhesive interactions. Microcontact printing of
      self-assembled monolayers and hot embossing imprint lithography approaches were
      integrated to manipulate focal adhesion assembly, cell adhesion, and cellular
      spreading and alignment. These micro- and nanopatterned substrates provide useful
      tools for the analyses of structure-function relationships in adhesive
      interactions.

PMID- 17450837
TI  - Surface structural biomimetics and the osteoinduction of calcium phosphate
      biomaterials.
AB  - From the point of view of materials, many natural tissues could be regarded as
      materials with certain nanostructure thus have special biological function. These
      natural nanostructures are generally formed under soft biological condition and
      show excellent biocompatibility and biological functions. To get materials with
      certain biological function, it is expectable to construct some nanostructure by
      mimicking the natural soft process. In this study, the porous biphasic calcium
      phosphate (BCP) ceramic was used to study the relationship of surface micro/nano
      structure and the biological function of osteoinductivity. Surface structural
      biomimetic was achieved by a soft technology of surface treating with simulated
      body fluid (SBF) or SBF containing protein molecules (BSA-SBF). The biological
      function of osteoinduction was tested by studying the bone formation in the
      samples implanted in dog nonosseous sites. The results showed that by the soft
      biomimetic process, the surface was re-constructed and the surface
      characteristics varied with the biomimetic process. The biological function of
      osteoinductivity depended on the surface characteristics. The present of protein
      molecules was likely to construct a surface structure which was different from
      that without the protein molecules and showed higher osteoinductivity. The study
      gave the evidence of material surface structural biomimetic to promote biological
      function as well as the possibility of the application of soft-nano technology to
      construct a micro/nano structural surface/interface of biomaterials with certain
      biological function.

PMID- 17450838
TI  - Micro-patterned nanofibrous biomaterials.
AB  - Nanofibrous materials made from bioabsorbable and biocompatible polymers have
      promising applications as tissue-engineered scaffolds. Genetic analysis of human
      umbilical vein endothelial cells (HUVEC) that attached to Poly(glycolide) (PGA)
      nanofibrous materials prepared via electrospinning methods demonstrated high
      expression of Integrin v and VEGF receptor genes, which are known angiogenesis
      markers. In order to improve the function of the PGA nanofibrous materials for
      tissue engineering applications, we used a micro-patterned template instead of a
      flat collector in the electrospinning process. "Micro-patterned nanofibrous
      material" demonstrated uniformly sized dents with diameters of 200 micrometers
      and depths of 36 micrometers. The dents were regularly spaced, with a 250
      micrometer space between two dents. These sizes are similar to that of the
      template. We will discuss further applications of this designable micro-patterned
      nanofibrous biomaterial.

PMID- 17450839
TI  - Preparation and characterization of hydroxyapatite/collagen nanocomposite gel.
AB  - The self-organized hydroxyapatite/colagen (HAp/Col) nanocomposite fiber
      (79.6/20.4 weight ratio) was synthesized by a co-precipitation method using
      Ca(OH)2, H3PO4, and Col as starting substances. The gelation of the nanocomposite
      is essential in the application of the scaffold for bone tissue engineering. We
      successfully prepared HAp/Col nanocomposite gels by a facile novel method using a
      sodium phosphate buffer at pH 6.8. The water-insoluble nanocomposite was
      homogeneously dispersed in the buffer to form a viscous mixture, and gels were
      obtained after incubating of the mixture at 37 degrees C. The mechanical strength
      of the gels was analyzed against the incubation time. The demineralized gel with
      EDTA had the typical nanostructure of native type I Col fibers from the results
      of scanning electron microscopy (SEM) and atomic force microscopy (AFM); the
      dense network of type I Col nano-fibers below 100 nm in diameter, and the
      periodic pattern of 68.8+/-4.4 nm (mean +/- SD) along the fibers were observed.
      The gelation of the HAp/Col nanocomposite in the buffer is attributed to the
      physical cross-linking through entanglement of the reconstituted Col fibrils.

PMID- 17450840
TI  - Drug-supported microparticles of calcium carbonate nanocrystals and its covering
      with hydroxyapatite.
AB  - Drug-supported spherical microparticles with below 3 microm in diameter of
      calcium carbonate (CC) nanocrystals were precipitated by a complex decomposition
      method from Na2CO3 and CaCl2 solutions with hydrocortisone phosphate (HyC). The
      HyC was completely incorporated into the microparticles and was adsorbed on the
      surface of nanocrystals. The crystal phases of vaterite and calcite were
      controlled by the addition of magnesium ions. Spherical microparticles of calcite
      cores and petal-shaped hydroxyapatite (HAp) outer layers were fabricated by
      soaking calcite into the SBF, or a supersaturated solution of phosphate ions to
      enhance the crystal growth of HAp.

PMID- 17450841
TI  - Lysozyme adsorption onto mesoporous materials: effect of pore geometry and
      stability of adsorbents.
AB  - In this paper, adsorption of lysozyme onto two kinds of mesoporous adsorbents
      (KIT-5 and AISBA-15) has been investigated and the results on the effects of pore
      geometry and stability of the adsorbents are also discussed. The KIT-5 mesoporous
      silica materials possess cage-type pore geometry while the AISBA-15 adsorbent has
      mesopores of cylindrical type with rather large diameter (9.7 nm). Adsorption of
      lysozyme onto AISBA-15 aluminosilicate obeys a Langmuir isotherm, resulting in
      pore occupation of 25 to 30%. In contrast, the KIT-5 adsorbents showed very small
      adsorption capacities for the lysozyme adsorption, typically falling in 6 to 13%
      of pore occupation. The cage-type KIT-5 adsorbents have narrow channel (4 to 6
      nm) where penetration of the lysozyme (3 x 3 x 4.5 nm) might be restricted. The
      KIT-5 adsorbent tends to collapse after long-time immersion in water, as
      indicated by XRD patterns, while the AISBA-15 adsorbent retains its regular
      structure even after immersion in basic water for 4 days. These facts confirm
      superiority of the AISBA-15 as an adsorbent as compared with the KIT-5 mesoporous
      silicates. This research strikingly demonstrates the selection of mesoporous
      materials is crucial to achieve efficient immobilization of biomaterials in
      aqueous environment.

PMID- 17450842
TI  - Collagen coating on hydroxyapatite surfaces modified with organosilane by
      chemical vapor deposition method.
AB  - Type I collagen was coated onto the modified surfaces of hydroxyapatite (HAp)
      sintered body. The interfacial interaction between collagen and HAp in a nano
      region was controlled by depositing the organosilane of n
      octadecyltrimethoxysilane (ODS: -CH3) or aminopropyltriethoxysilane (APTS: -NH2)
      with a chemical vapor deposition method. The surfaces were elaborated by X-ray
      photoelectron spectroscopy, zeta-potential, and contact angle measurements; the
      Si and/or N peaks were detected, and the contact angles and surface energies were
      apparently different on the modified surfaces. The morphologies of collagen
      adsorbed on the surfaces of HAp and HAp deposited with APTS were similar, however
      that of the surface with ODS was apparently different, due to the hydrophobic
      interaction between the organic head group of -CH3 and residual groups of
      collagen.

PMID- 17450843
TI  - Synthesis and characterization of metal ions containing hydroxyapatite
      microparticles with high specific surface area.
AB  - Zinc and/or iron ions containing hydroxyapatite (HA) microparticles, which had
      twice as high specific surface area and higher pore volumes compared with the
      pure HA, were fabricated by a spray drying method; the zinc and/or iron ions were
      incorporated into the constitutional nanocrystals with below 20 nm in size in
      preparing. The small amount of carbonate ions was substituted in the phosphate
      group. The particle sizes were distributed in the range of 1 to 20 microm in
      diameter and its averaged size was approximately 6 microm. The microparticles
      with a spherical shape showed a single phase of HA and, after treated at higher
      temperature than 800 degrees C, had the high crystallite HA and the other phase
      of metal oxide such as ZnO or Fe2O3. The microparticles with higher specific
      surface area will be applicable for the drug delivery carriers of proteins.

PMID- 17450844
TI  - Motility and structural polymorphism of polymer-actin complex gel.
AB  - We report a soft gel machine reconstructed from muscle proteins. We have found
      that chemically cross-linked polymer-actin complex gel can move on myosin coated
      surface with a velocity as high as that of native F-actin, by coupling to ATP
      hydrolysis. Additionally, it is shown that the velocity and motional pattern of
      polymer-actin complex gel depends on the morphology of polymer-complex gels.
      Since the designing of functional actuator into well-defined size and morphology
      is important, the structural behavior of polymer-actin complexes has been
      investigated. This result shows that the morphology and growth size of polymer
      actin complex can be controlled by change of electrostatic interaction between F
      actins and polycations. Our results indicate that bio actuator with desired shape
      can be created by using polymer-actin complex.

PMID- 17450845
TI  - Nano-sized ceramic particles of hydroxyapatite calcined with an anti-sintering
      agent.
AB  - Nano-sized crystals of calcined hydroxyapatite (HAp) having spherical
      morphologies were fabricated by calcination at 800 degrees C for 1 h with an anti
      sintering agent surrounding the original HAp particles and the agent was
      subsequently removed by washing after calcination. The original HAp particles
      were prepared by a modified emulsion system, and surrounded with poly(acrylic
      acid, calcium salt) (PAA-Ca) by utilizing a precipitation reaction between
      calcium hydroxide and poly(acrylic acid) adsorbed on the HAp particle surfaces in
      an aqueous medium. In the case of calcination without PAA-Ca, micron-sized
      particles consisting of sintered polycrystals were mainly observed by scanning
      electron microscopy, indicating the calcination-induced sintering among the
      crystals. On the other hand, most of the crystals calcined with the anti
      sintering agent were observed as isolated particles, and the mean size of the HAp
      crystals was around 80 nm. This result indicates that PAA-Ca and its thermally
      decomposed product, CaO, surrounding the HAp crystals could protect them against
      calcination-induced sintering during calcination at 800 degrees C. The HAp
      crystals calcined with PAA-Ca showed high crystallinity, and no other calcium
      phosphate phases could be detected.

PMID- 17450846
TI  - Preparation of chitosan nanofiber tube by electrospinning.
AB  - Water-insoluble chitosan nanofiber sheets and tubes coated with chitosan-cast
      film were prepared by electrospinning. When as-spun chitosan nanofiber sheets and
      tubes were immersed in 28% ammonium aqueous solution, they became insoluble in
      water and showed nanofiber structures confirmed by SEM micrography. Mechanical
      properties of chitosan nanofiber sheets and tubes were improved by coating with
      chitosan-cast film, which gave them a compressive strength higher than that of
      crab-tendon chitosan, demonstrating that chitosan nanofiber tubes coated with
      chitosan-cast film are usable as nerve-regenerative guide tubes.

PMID- 17450847
TI  - Differences of internal structures between amphiphilic and hydrophobic block
      copolymer nanoparticles.
AB  - In this report, we show a novel and simple preparation method for obtaining block
      copolymer nanoparticles. Regular-sized polymer nanoparticles are formed after
      evaporation of a good solvent from a polymer solution containing a non-volatile
      poor solvent and the volatile good solvent. Nanoparticles of poly(styrene-b
      sodium acrylate), poly(styrene-b-4-vinylpyridine), and poly(styreneb-isoprene)
      were prepared by using this method. We also discuss the difference of internal
      structures between amphiphilic and hydrophobic block-copolymer nanoparticles.
      From the results of scanning transmission electron microscope (STEM) imaging, the
      particles of amphiphilic block-copolymers have hollow structures were observed.
      On the other hand, the particles of a hydrophobic block-copolymer form lamellar
      micro-phase separation structures.

PMID- 17450848
TI  - Reconstruction of bone fenestration on mandiblar by the guided bone regeneration
      methods with beta-TCP/PLGC membranes.
AB  - Guided Bone Regeneration (GBR) is a method for bone tissue regeneration. In this
      method, membranes are used to cover bone defects and to block the invasion of the
      surrounding soft tissues. It would provide sufficient time for the osteogenic
      cells from bone marrow to proliferate and form new bony tissues. In spite of the
      potential usefulness of this method, no appropriate materials for the GBR
      membrane have been developed. Here we design the ideal mechanical properties of
      the GBR membranes and created novel materials, which is the composite of beta
      tricalcium phosphate (beta-TCP) and block copolymer of L-lactide, glycolide, and
      epsilon-caplolactone (PLGC). In the animal experiments with the use of the GBR
      membranes for large bone defects, we observed significant enhancement in the bone
      regeneration after 12 weeks implantation and proved the effectiveness of the
      materials.

PMID- 17450849
TI  - Biodegradable nanomats produced by electrospinning: expanding multifunctionality
      and potential for tissue engineering.
AB  - With increasing interest in nanotechnology, development of nanofibers (n-fibers)
      by using the technique of electrospinning is gaining new momentum. Among
      important potential applications of n-fiber-based structures, scaffolds for
      tissue-engineering represent an advancing front. Nanoscaffolds (n-scaffolds) are
      closer to natural extracellular matrix (ECM) and its nanoscale fibrous structure.
      Although the technique of electrospinning is relatively old, various improvements
      have been made in the last decades to explore the spinning of submicron fibers
      from biodegradable polymers and to develop also multifunctional drug-releasing
      and bioactive scaffolds. Various factors can affect the properties of resulting
      nanostructures that can be classified into three main categories, namely: (1)
      Substrate related, (2) Apparatus related, and (3) Environment related factors.
      Developed n-scaffolds were tested for their cytocompatibility using different
      cell models and were seeded with cells for to develop tissue engineering
      constructs. Most importantly, studies have looked at the potential of using n
      scaffolds for the development of blood vessels. There is a large area ahead for
      further applications and development of the field. For instance, multifunctional
      scaffolds that can be used as controlled delivery system do have a potential and
      have yet to be investigated for engineering of various tissues. So far, in vivo
      data on n-scaffolds are scarce, but in future reports are expected to emerge.
      With the convergence of the fields of nanotechnology, drug release and tissue
      engineering, new solutions could be found for the current limitations of tissue
      engineering scaffolds, which may enhance their functionality upon in vivo
      implantation. In this paper electrospinning process, factors affecting it, used
      polymers, developed n-scaffolds and their characterization are reviewed with
      focus on application in tissue engineering.

PMID- 17450850
TI  - Effects of carrier gas dynamics on single wall carbon nanotube chiral
      distributions during laser vaporization synthesis.
AB  - We report on the utility of modifying the carrier gas dynamics during laser
      vaporization synthesis to alter the single wall carbon nanotube (SWNT) chiral
      distribution. SWNTs produced from an Alexandrite laser using conventional Ni/Co
      catalysts demonstrate marked differences in chiral distributions due to effects
      of helium gas and reactor chamber pressure, in comparison to conventional
      subambient pressures and argon gas. Optical absorption and Raman spectroscopies
      confirm that the SWNT diameter distribution decreases under higher pressure and
      with helium gas as opposed to argon. Fluorescence mapping of the raw soots in
      sodium dodecylbenzene sulfonate (SDBS)-D2O was used to estimate the relative (n,
      m)-SWNT content of the semiconducting types. A predominance of type II structures
      for each synthesis condition was observed. The distribution of SWNT chiral angles
      was observed to shift away from near-armchair configurations under higher
      pressure and with helium gas. These results illustrate the importance of gas type
      and pressure on the condensation/cooling rate, which allows for synthesis of
      specific SWNT chiral distributions.

PMID- 17450851
TI  - Carbon nanotubes grown on stainless steel to form plate and probe electrodes for
      chemical/biological sensing.
AB  - This paper describes the fabrication and evaluation of carbon nanotube (CNT)
      electrodes grown on stainless steel (SS) plate and wire for electrochemical
      sensor applications. Multi-wall carbon nanotubes with different diameters were
      grown on the SS plate and wire by chemical vapor deposition from an ethylene
      precursor. The SS provides a good electrical and mechanical connection to the
      CNT, and the SS is a tough substrate. The SS part of the electrode was
      electrically insulated from the analyte so that only the CNT were active in
      sensing. Cyclic voltammetry for the reduction of 6 mM K3Fe(CN)6 in a 1.0 M KNO3
      supporting electrolyte was performed to examine the redox behavior of the CNT-SS
      electrode. The cyclic voltammograms showed sigmoidal-like shapes, indicating that
      mass transport around the electrodes is dominated by radial diffusion. Based on
      the cyclic voltammograms, the effective area of the CNT-SS electrodes and the
      number of individual CNTs were estimated. These results indicate that the CNT-SS
      plate and wire electrodes are good candidates to develop practical in vivo
      biosensors.

PMID- 17450852
TI  - Thermal-mechanical properties of a graphitic-nanofibers reinforced epoxy.
AB  - We previously developed a series of reactive graphitic nanofibers (r-GNFs)
      reinforced epoxy (nano-epoxy) as composite matrices, which have shown good
      wetting and adhesion properties with continuous fiber. In this work, the thermal
      mechanical properties of the nano-epoxy system containing EponTM Resin 828 and
      Epi-cure Curing Agent W were characterized. Results from three-point bending
      tests showed that the flexural strength and flexural modulus of this system with
      0.30 wt% of reactive nanofibers were increased by 16%, and 21% respectively, over
      pure epoxy. Fracture toughness increased by ca. 40% for specimens with 0.50 wt%
      of r-GNFs. By dynamic mechanical analysis (DMA) test, specimens with 0.30 wt% of
      r-GNFs showed a significant increase in storage modulus E' (by ca. 122%) and loss
      modulus E" (by ca. 111%) with respect to that of pure epoxy. Also thermo
      dilatometry analysis (TDA) was used to measure dimensional change of specimens as
      a function of temperature, and then, coefficients of thermal expansion (CTE)
      before and after glass transition temperature (Tg) were obtained. Results implied
      that nano-epoxy materials had good dimensional stability and reduced CTE values
      when compared to those of pure epoxy.

PMID- 17450853
TI  - Homogeneous precipitation of Dy2O3 nanoparticles-effects of synthesis parameters.
AB  - The experimental parameters that control the size and size distribution of
      dysprosium oxide nanoparticles synthesized by homogeneous precipitation technique
      have been systematically investigated. The particles were characterized with
      respect to their size, shape, and thermal decomposition behavior. It was found
      that the precipitated particles were spherical, uniform in size, and amorphous,
      which upon heating in air, decomposed into the oxide form with no change in
      morphology. The size and size distribution of the particles showed strong
      dependence on the metal cation concentration ([Dy3+]) and weak dependence on urea
      concentration and aging time. In addition, the presence of chlorine ions (Cl-)
      was found to have significant effect on the growth and agglomeration of the
      particles. Aggregation mechanism as the growth mechanism is offered to explain
      the effects of these synthesis parameters on the morphology, size, and size
      distribution of dysprosium oxide particles.

PMID- 17450854
TI  - Lamellar phase supported synthesis of colloidal gold nanoparticles, nanoclusters,
      and nanowires.
AB  - Gold nanoparticles (Au NP) have been synthesized in aqueous phase under ambient
      conditions in the presence of a series of various cationic double chain as well
      as dimeric (gemini) surfactants. The spacer chain and twin tail length of these
      surfactants has been systematically varied to see the effect of hydrophobicity on
      their capping ability. It has been observed that the increase in the length of
      spacer chain (from 12-2-12 to 12-6-12) and twin tails (from 10-2-10 to 14-2-14)
      significantly increases the lamellar phase formation and which in return acts as
      a wonderful template to accommodate the NP in the form of nanoclusters and
      nanowires. The lamellar phase practically facilitates the nucleation of Au
      degrees and produces large NP (15 +/- 2 nm). All reactions have also been carried
      out in the presence of beta-cyclodextrin (CYC) which has strong ability to
      complex with surfactant tail. The presence of CYC induces a tendency to form
      nanowire and it is more prominent in the case of surfactants with longer spacer
      group.

PMID- 17450855
TI  - Enhanced delivery of bioactive molecules to intracellular environments utilizing
      a cytosolically reducable grafted analog of polyethylenimine.
AB  - The use of cationic polymers for the delivery of DNA to mammalian cells has
      generated significant interest due to the intrinsic properties associated with
      these delivery vector systems. One particular system utilizing polyethylenimine
      (PEI) has been rigorously investigated. A major drawback associated with PEI is
      the cytotoxicity of the vector/delivery system. In an effort to combat this
      adverse side effect we have synthesized a novel random block copolymer based upon
      low molecular weight PEI. Here we report the grafting of Traut's reagent to
      residual primary amines of PEI to form a random block copolymer. The copolymer
      introduces a disulfide bridge upon oxidation of Traut's reagent capable of
      intracellular reduction. We confirm the successful grafting of this agent through
      FTIR and C-13 NMR. Molecular weight determination of the grafted copolymer was
      performed through HPLC-SEC and light scattering experiments. This polymer retains
      the ability to deliver GFP encoding plasmid DNA to 3T3 fibroblasts. Transfection
      levels were found to be approximately 90%. Transfection of T7 RNA dependent DNA
      polymerase was also performed utilizing our copolymer. We find successful
      activation of a virally introduced RNA transcript.

PMID- 17450856
TI  - Functionalized nano-magnetic particles for an in vivo delivery system.
AB  - Nanotechnologies to allow the nondisruptive introduction of carriers in vivo have
      wide potential for therapeutic delivery system. We have prepared functional nano
      magnetic particles (d = 3 nm) by silanization with (3-aminopropyl)
      triethoxysilane. For the purpose of functionalizing the surface of the
      nanoparticles with amino groups for subsequent cross-linking with pharmaceuticals
      and biomolecules. The extremely small particles were successfully introduced into
      living cells without any further modification to enhance endocytic
      internalization, such as the use of a cationic help. The cells containing the
      internalized particles continued to thrive, indicating that the particles have no
      inhibition effect for mitosis. In addition, the particles could be incorporated
      into the subcutaneous tissue of mouse's ear from ear skin and were able to be
      localized upon application of an external magnetic field. The functionalized nano
      magnetic particles are expected to be useful as a new delivery tool.

PMID- 17450857
TI  - Electric field assisted growth of self-organized CdS films: size dependent
      structural and optical properties.
AB  - This paper presents a systematic study of electric field assisted growth of self
      organized cadmium sulphide (CdS) quantum dots (Q-CdS). CdS thin films of self
      organized quantum dot like structure with different particle size have been
      successfully deposited simply by varying the concentration of surfactant in the
      reaction matrix. The model to describe the self-organization is also discussed.
      The size of CdS nanoparticles can be altered from 68 nm (corresponding to bulk)
      to 2 nm. The structural, optical, and morphological properties of Q-CdS films
      have been investigated. A blue shift has been observed in optical absorption and
      photoluminescence spectra. The strained growth of Q-CdS films has been observed.
      The microstructural strain calculated from peak broadening reveals an increase in
      strain with decreasing particle size. This study may provide a convenient method
      to deposit size selective and organized nanocrystalline semiconductor thin films.

PMID- 17450858
TI  - Microwave assisted semi-solvothermal synthesis of nanocrystalline barium
      titanate.
AB  - In an endeavor to synthesize tetragonal nanocrystallites of BaTiO3 at much
      reduced reaction time, we explored the possibility of performing microwave
      assisted semi-solvothermal reaction by using Ba(OH)2 . 8H2O and amorphous
      titanium hydrous gel as precursors and 1,4-butanediol and water as solvent.
      Typically, such a microwave assisted reaction was accomplished within 2 hrs at
      220 degrees C as against 12 hrs required in conventional approach. The
      crystallized BaTiO3 powders (microwave assisted as well as conventionally
      processed for reference) were characterized by X-ray diffraction, thermal
      analysis, infrared spectroscopy, Raman spectroscopy, scanning electron
      microscopy, transmission electron microscopy, and atomic force microscopy. We
      have detected metastable cubic phase by XRD while locally symmetric tetragonal
      phase by Raman spectroscopy in case of conventional semi-solvothermal processing.
      On the contrary, we could detect co-existence of tetragonal and cubic phases by
      XRD and only tetragonal phase by Raman spectroscopy in case of microwave assisted
      semi-solvothermal processing. The TEM analysis indicates typical particle size
      distribution in the range of approximately 20 to 80 nm for conventionally
      processed powder while that in the range of approximately 20 to 50 nm for
      microwave processed powder. HRTEM images evince the distortion from an ideal
      cubic structure in case of microwave processed powder which can be correlated
      with anisotropic lattice contraction during the microwave induced heating. AFM
      analysis exhibited relatively less aggregation of nanoparticles for microwave
      assisted process.

PMID- 17450859
TI  - Formation of self-assembled glycolipid nanotubes with bilayer sheets.
AB  - Rolled-up morphology of bilayer sheets in a self-assembled glycolipid nanotube
      (LNT) in water was carefully examined by using a cryogenic transmission electron
      microscope (cryo-TEM) with a rapid-freezing specimen-preparation technique. The
      LNTs were obtained under a series of self-assembly conditions: boiling of an
      aqueous dispersion of glycolipid N-(11-cis-octadecenoyl)-beta-D
      glucopyranosylamine, subsequent gradual cooling, and incubation at room
      temperature for several days. Cryo-TEM images revealed that the LNT walls consist
      of a multilayer structure with interlayer distance of about 4.7 nm. These layers
      correspond to constituent lipid bilayers. From the result of precise cryo-TEM
      observations and analyses, we confirmed the rolled-up morphology of the lipid
      bilayer sheets in a complete self-assembled glycolipid nanotube.

PMID- 17450860
TI  - Structural, magnetic, and electron transport studies on nanocrystalline layered
      manganite La1.2Ba1,8Mn2O7 system.
AB  - The structure property relationship for Ru doped La1.2Ba1.8Mn2-RuxO7 system has
      been studied systematically. The system crystallizes in the single-phase
      tetragonal structure with space group of 14/mmm. The unit cell volume is found to
      increase with Ru doping. The sheet type microstructure could be seen in this
      system, which is important for anisotropic nature of layered structure. The
      crystallite size is found to be 25 nm indicating nanocrystalline nature of the
      system. Ferromagnetic to paramagnetic (Tc) transition above the room temperature
      is observed in all except the highest doped Ru (x = 1.0) where the Tc is 254 K
      using a.c. susceptibility measurement. The large values of magnetoresistance for
      the x = 0.0 sample at 10 K is found to be 57% and 64% at applied fields of 5 and
      10 T, respectively.

PMID- 17450861
TI  - Spectroscopic characterization of nanocrystalline chromium nitride (CrN).
AB  - Nanocrystalline chromiuim nitride has been synthesised by direct gas phase
      nitridation of nanocrystalline chromia at 1100 degrees C in ammonia-atmosphere.
      XRD of this material showed formation of single phase CrN with particle size
      around 20 nm. AFM studies showed particle distribution along with some soft
      agglomerated nanostructures. Nanocrystalline Cr2O3 and partially-as well as fully
      -converted nanocrystalline CrN were also investigated using various spectroscopic
      techniques like XPS, FT-IR, and Raman for gaining insight into the conversion
      pathways. Spectroscopic investigations of these materials clearly indicate that
      complete conversion of CrN occurs by nitriding at 1100 degrees C for 4 hrs. The
      salient spectroscopic features of these nanocrystalline materials with respect to
      their microcrystalline counterparts are discussed.

PMID- 17450862
TI  - Dip-pen lithography using pens of different thicknesses.
AB  - A laboratory method to produce AFM tips of different sizes has been developed
      based on laser irradiation of the commercial silicon nitride tips. A few shots of
      60 mJ at 355 nm were found adequate to induce the desired bluntness from 40 nm to
      500 nm in a controlled way. Dip-pen nanolithography (DPN) has been performed with
      the blunt tips using a colloidal ink consisting of Pd nanocrystals coated with
      polyvinyl pyrrolidone. The line patterns drawn bear a direct relation with the
      tip morphology, wider the tip, broader are the patterns, in general. The rate of
      deposition also increases with the tip dimension, but is not as much proportional
      for larger tips. The study highlights the potential ability of DPN in integrating
      nano and microelectronics.

PMID- 17450863
TI  - Synthesis and characterization of Mo6S4.5I4.5 nanowires.
AB  - We report on the synthesis and characterization of new a nano-wire-like material
      with chemical formula Mo6S4.5I4.5. The material can be synthesized in a single
      step reaction from elements in bulk quantities. The material has a fur-like
      appearance and is composed of nanowires that are weakly bound in bundles. Bundles
      itself can be dispersed using an ultrasonic bath in various organic solvents and
      water. Elemental analysis, X-ray diffraction, thermal analysis (TG, DTA), and
      electron microscopy were used to characterize the new material in the shape of
      nanowires. Due to their monodisperse and metallic nature, molybdenum-sulphur
      iodine nanowires are an interesting alternative to carbon nanotubes for some
      applications.

PMID- 17450864
TI  - Study of Sago starch-CdS nanocomposite films: fabrication, structure, optical and
      thermal properties.
AB  - A synthetic procedure for the preparation of nanocomposite films of sago starch
      and CdS nanoparticles was introduced. The films were characterized using optical,
      structural, and thermal techniques. The formation of nanostructured CdS in the
      starch matrix was confirmed by a blue shift in the onset of absorption in the UV
      VIS spectra of the nanocomposites. The average size of the nanoparticles varied
      from 3.6 to 5 nm, depending on the initial concentration of cadmium acetate
      during the nanocomposite preparation. Fluorescence measurements of the sago-CdS
      nanocomposite film showed broad emission in the orange-red part of the spectrum.
      DSC and TGA analyses revealed significant effects of CdS nanoparticles on the
      thermal properties of the starch matrix.

PMID- 17450865
TI  - Polymeric nanocomposites of functionalized carbon nanotubes synthesized in
      supercritical CO2.
AB  - A novel method to synthesize single-wall carbon nanotube (SWNT)/poly(methyl
      methacrylate) (PMMA) nanocomposite by in-situ polymerization in supercritical CO2
      is presented. The surfaces of the SWNT bundles were first functionalized with
      amino ethyl methacrylate (AEMA) followed by co-polymerization with methyl
      methacrylate. Supercritical fluid enhanced the diffusivity of monomer and
      facilitated the growth of tethered PMMA chains near the entanglement area and the
      interstitial space of the SWNT bundles. Partial debundling and disentanglement of
      the SWNT bundles and an enhanced dispersion in the polymer matrix were observed
      under SEM and TEM. After the removal of the polymer matrix physically attached to
      the nanotubes, it is found that the nanotubes were covered by tethered PMMA
      chains, which were a few nanometers in thickness. This work creates a route for
      improving impregnation and dispersion in SWNT composites; the same process can be
      extended to other vinyl polymers.

PMID- 17450866
TI  - In situ reaction on Cu(OH)2 nanoribbons for controlling growth of nanorods arrays
      of copper oxalate.
AB  - Cu(OH)2 nanoribbons template provides a simple way for producing arrays of copper
      oxalate nanorods and assemblies with controllable size and shape of the arrays of
      copper oxalate in situ reaction on Cu(OH)2 nanoribbons. The observations of
      scanning electron microscopy and characterization of X-ray powder diffraction and
      Fourier transmission infrared spectrometry show formation of the arrays of cubic
      column nanorods, nanotubes, and corn-like nanorods of CuC2O4 by controlling the
      concentration of oxalate solution and reaction time. We believe this approach can
      also be applied for synthesis of inorganic and inorganic/organic material
      architectures.

PMID- 17450867
TI  - Thermal, structural, optical, and dielectric properties of (100 - x)Li2B4O7 -
      x(BaO-Bi2O3-Nb2O5) glasses and glass-nanocrystal composites.
AB  - Transparent glasses in the system (100 - x)Li2B4O7 - x(BaO-Bi2O3-Nb2O5) (x = 10,
      20, and 30) were fabricated via the conventional melt-quenching technique. The
      amorphous and glassy characteristics of the as-quenched samples were established
      by the differential thermal analyses (DTA) and X-ray powder diffraction (XRD)
      studies. Glass-nanocrystal composites (GNCs) i.e., the glasses embedded with
      BaBi2Nb2O9 (BBN) nanocrystals (10-50 nm) were produced by heat-treating the as
      quenched glasses at temperatures higher than 500 degrees C. Perovskite BBN phase
      formation through an intermediate fluorite-like phase in the glass matrix was
      confirmed via XRD and transmission electron microscopic (TEM) studies. The
      optical transmission properties of these GNCs were found to have a strong
      compositional (BBN content) dependence. The refractive index (n = 1.90) and
      optical polarizability (alphao = 15.3 x 10(-24) cm3) of the GNC (x = 30) were
      larger than those of as-quenched glasses. The temperature dependent dielectric
      constant (epsilonr) and loss factor (D) for the glasses and GNCs were determined
      in the 100-40 MHz frequency range. The epsilonr was found to increase with
      increase in heat-treatment temperatures, while the loss of the glass
      nanocomposites was less than that of as-quenched glasses. The sample heat-treated
      at 620 degrees C/1 h (x = 30) exhibited relaxor behavior associated with a
      dielectric anomaly in the 150-250 degrees C temperature range. The frequency
      dependence of the dielectric maximum temperature was found to obey the Vogel
      Fulcher relation (Ea = 0.32 eV and Tf = 201 K).

PMID- 17450868
TI  - Characterization of fine grain Ba0.995Y0.005TiO3 ceramics obtained from gel
      precursor nanopowder.
AB  - Using an acetate-alkoxide sol-gel route in which the precursors are barium
      acetate, yttrium isopropoxide and titanium diisopropoxide bis-acetylacetonate, we
      prepared a ferroelectric material with the formula: Ba1-xYxTiO3, x = 0.005. SEM
      analysis showed a polymeric microstructure of the gel due to the chelated
      titanium alkoxide precursor used as starting materials. The evolution of the
      structure and microstructure of the precursor gel heated at temperatures up to
      1000 degrees C was studied by various techniques. The powder obtained by heating
      the gel at 1100 degrees C presented a homogeneous structure consisting of
      submicronic particles (approximately 200 nm). XRD and SAED analyses revealed that
      Ba0.995Y0.005TiO3 nanocrystals of about 5-10 nm appeared at 600 degrees C,
      together with BaCO3. The presence of barium carbonate was identified also by IR
      spectroscopy and thermal analyses. The ceramics obtained from the as-prepared
      powder presented good dielectric properties (capacitance = 840 pF/dielectric
      constant = 3860 and dielectric loss (tandelta) = 0.078 at Curie temperatures of
      120-121 degrees C).

PMID- 17450869
TI  - Fabrication and size-dependent optical properties of copper/lophine core/shell
      nanocomposites.
AB  - Copper/lophine core/shell nanocomposites were fabricated through the self
      assembly of lophine on the surfaces of copper nanostructures. The growth of the
      lophine shells was induced by the cooperation of coordination and several other
      noncovalent interactions. The dimensions, structures, and morphologies of the
      nanocomposites can be readily controlled by just altering the size and morphology
      of the copper core. The formation mechanism of the core/shell nanocomposites was
      put forward on the basis of a series of characterizations. The optical properties
      of the shell lophine layer can be tuned by changing the size of the copper core.

PMID- 17450870
TI  - Release of doxorubicin from unstabilized and stabilized micelles under the action
      of ultrasound.
AB  - Polymeric micelles are being investigated as chemotherapy drug delivery carriers
      using ultrasound as a trigger mechanism. The aim of this paper is to measure the
      release of Doxorubicin (Dox) from the core of unstabilized Pluronic P105
      micelles, Pluronic P105 micelles stabilized with an interpenetrating network of
      N,N-diethylacrylamide, and micelles of poly(ethylene oxide)-b-poly (N
      isopropylacrylamide)-b-poly(oligolactylmethacrylate) with stabilized cores. An
      ultrasonic exposure chamber with fluorescence detection was used to measure the
      release of the antineoplastic agent from both stabilized and unstabilized
      micelles. The release of Dox at 37 degrees C from unstabilized Pluronic appears
      to be several times higher than release from the more stabilized and crosslinked
      copolymers at the same temperature. Although there is a difference in the amount
      of release between the different compounds, the onset of release occurs at about
      the same ultrasonic power density for all carriers investigated in this study.
      The threshold of drug release for all the compounds correlates to the emergence
      of subharmonic peaks detected in the acoustic spectra. We hypothesize that
      shearing events caused by cavitating bubbles play an important role in the
      acoustically activated release of chemotherapy agents delivered from various
      polymeric drug delivery vehicles.

PMID- 17450871
TI  - Synthesis of beaded and entwined carbon nanofibers in Ni:Al alloy catalyst.
AB  - This paper reports two new types of carbon nanofibers synthesis by thermal
      decomposition of n-hexane in presence of Ni-Al alloy in hydrogen atmosphere at
      1100 degrees C. One type is "beaded fibers" in which spherical carbon beads
      (approximately 1 microm) are regularly grown from outer surface of fibers
      (approximately 0.3 microm). The other new microstructure is "entwined fibers" in
      which multiple nanofibers of diameter approximately 100 nm grow self-entwined
      like a braid of hair. Both bead-fiber bonding (in beaded fibers) and fiber-fiber
      interaction (in entwined fibers) are strong to be detached/unfolded by 30-min
      ultrasonication.

PMID- 17450872
TI  - Nanocrystalline CaO as adsorbent to remove COD from paper mill effluent.
AB  - Porous nanocrystalline CaO has been prepared by the solution combustion process
      using calcium nitrate as oxidizer and glycine as a fuel. As prepared calcium
      oxide has been characterized using powder X-Ray Diffraction (XRD), BET surface
      area, and Scanning Electron Microscopy (SEM). The powder XRD pattern confirms the
      crystallinity and phase purity of the powder. The particle size of the powder
      obtained from Scherrer's formula lies in the range of 37-53 nm. The particles are
      loosely agglomerated and spherical in shape as observed by SEM. The specific
      surface area of the powder is 18.5 m2/g and the average pore diameter obtained
      from N2-desorption isotherm is approximately 5.2 nm. Batch shaking process was
      performed using CaO as adsorbent with effluent collected from pulp and paper mill
      to remove chemical oxygen demand (COD). The COD removal capacity of the CaO is
      approximately 93%.

PMID- 17450873
TI  - Mean magnetic moment of polydisperse superparamagnetic nanoparticles: correlation
      between grain size and magnetic moment distributions.
AB  - The field dependence of magnetization in superparamagnetic systems can be fitted
      using a set of Langevin contributions characterized by their particle densities
      and their magnetic moments. In fact, these contributions are just partial average
      values over the actual magnetic moment distribution of the system. The
      achievement of the most adequate mean magnetic moment is non-trivial and depends
      on the characteristics of the moment distribution and the applied magnetic field
      range. As an example, results have been applied to a nanocrystalline alloy.

PMID- 17450874
TI  - Templated growth of carbon nanotubes with controlled diameters using organic
      organometallic block copolymers with tailored block lengths.
AB  - Block copolymer thin films fabricated from polystyrene-polyferrocenylsilane (PS-b
      PFS) block copolymers on silicon substrates were used as precursors of well
      ordered, nanosized growth catalysts for carbon nanotubes (CNTs). The size of the
      catalytic domains was tuned by changing the molecular weight of the block
      copolymer, enabling control of the diameter of the CNTs grown from these
      substrates. CNT growth on catalytic substrates with larger organometallic domain
      sizes, using acetylene as a carbon source, resulted in enhanced amounts of CNT
      deposition compared to smaller PFS domains, which exhibited low catalytic
      activity. The inner and outer diameters of the multi-walled CNTs obtained were
      typically 8 and 16 nm, respectively, and were not influenced by the catalytic
      domain sizes. Various annealing strategies in inert or in hydrogen atmosphere
      were investigated. The use acetylene with an additional hydrogen flow as gas feed
      resulted in a significant increase in deposition on all PS-b-PFS decorated
      substrates. Under these conditions, the CNT diameters could be controlled by the
      catalyst domain sizes, resulting in decreasing diameters with decreasing domain
      sizes. Multiwalled CNTs with inner and outer diameters of 4 and 7 nm,
      respectively, and a narrow diameter distribution were obtained.

PMID- 17450875
TI  - Ellipsoidal core-shell dielectric-gold nanostructure: theoretical study of the
      tunable surface plasmon resonance.
AB  - The dependence of surface plasmon resonance (SPR) characters of core-shell
      structure ellipsoidal nanorods was investigated as functions of the gold shell
      width and dielectric constant. A dipole-limit calculation indicated that, there
      are four SPR absorption peaks occur. The two shorter wavelength peaks are
      attributed to the transverse resonances, whereas the two longer wavelength peaks
      are attributed to the longitudinal resonances. Both transverse and longitudinal
      resonances are split into inner surface and outer surface modes, respectively.
      When the core size is a fixed value, the two transverse surface plasmon peaks red
      shift as the gold shell width is increased. On the other hand, both the inner and
      outer surface modes attributed to the longitudinal surface plasmon peaks blue
      shifts distinctly and nonlinearly. Further more, both the inner and outer surface
      plasmon modes are also dependent on the embedding medium and core dielectric
      constant. The longitudinal SPR from inner surface is more sensitive to the core
      dielectric constant, whereas the longitudinal SPR from outer surface is more
      sensitive to the surrounding medium.

PMID- 17450876
TI  - Synthesis of one-dimensional sodium titanate nanostructures.
AB  - We synthesized sodium titanate nanotubes and nanowires using TiB2 and TIN as the
      starting materials, respectively in a hydrothermal process. The experimental
      results indicate that the reaction temperature influences the morphology of the
      product significantly. The nanowires were formed above 170 degrees C. Nanotubes
      were obtained below 140 degrees C. The synthesized nanotubes exhibit a
      crystallized multi-wall structure. The inner diameter was found to be ca. 5 nm.
      The diameter of the nanowires was found to be ca. 50 nm. The characteristic
      lengths was in the order of tens micrometers.

PMID- 17450877
TI  - Interaction of erythrocytes with magnetic nanoparticles.
AB  - Internalization of biocompatible magnetic nanoparticles by red blood cells (RBCs)
      is a key issue for opportunities of new applications in the biomedical field. In
      this study, we used in vitro tests to provide evidences of magnetic nanoparticle
      internalization by mice red blood cells. The internalization process depends upon
      the nanoparticle concentration and the nanoparticle hydrodynamic radii. The cell
      internalization of surface-coated maghemite nanoparticles was indirectly tracked
      by Raman spectroscopy and directly observed using transmission electron
      microscopy. The observation of nanoparticle cell uptaking using in vitro
      experiments represents an important breakthrough for the application of
      nanomagnetism in diagnosis and therapy of RBC-related diseases.

PMID- 17450878
TI  - Direct synthesis of polyoxometalates-functionalized mesoporous hybrid silicas.
AB  - Novel polyoxometalates (POMs)-functionalized mesoporous hybrid silicas
      (SiW11/MHS) were synthesized for the first time by the co-condensation of
      tetraethoxysilane (TEOS) with Keggin-type monovacant SiW11 in the presence of
      block copolymer EO20PO70EO20 (P123). The as-obtained SiW11/MHS samples were
      characterized by FT-IR, UV/DRS, XRD, ICP-AES, and N2 adsorption-desorption
      measurements. It is shown that not only a hexagonal packing of channels with
      homogeneous pore diameter is obtained, but also Keggin units remain perfectly in
      the hybrid materials, and Si species insert into the vacancies of lacunary SiW11
      during the synthesis to form SiW11Si2 structure, which condenses with the
      framework of mesoporous silica thus grafting POM molecules onto the pore wall of
      mesoporous silica by covalent linkage. This linkage results in a firmer
      immobilization of POMs on the mesoporous material. The water-leaching percent of
      POMs in the hybrid material is much less than those in the impregnated samples.
      Therefore, the synthesis strategy for the hybrid material is significant for
      acquiring supported POM catalysts of high efficiency and practicability.

PMID- 17450879
TI  - Crabwise ZnO nanowires: growth and field emission properties.
AB  - Crabwise ZnO nanowires with an average length of 5 microm and an average diameter
      of 30 nm were selectively grown on ZnO:Ga/glass templates. Cathodoluminescence
      measurement indicated that the crystal quality of the crabwise ZnO nanowires was
      good. With an applied voltage of 120 V, the crabwise ZnO nanowire field emitters
      gave an emission current of 0.1 mA/cm2. Moreover, the field enhancement factor,
      beta, of the crabwise ZnO nanowires was approximately 980.

PMID- 17450880
TI  - Field emission of GaN-filled carbon nanotubes: high and stable emission current.
AB  - Field electron emission of GaN-filled carbon nanotubes, grown by microwave plasma
      enhanced chemical vapor deposition, was investigated. The detailed structural
      characterization shows that the filled nanotube has a GaN-core/C-shell structure,
      in which the GaN wire corresponds to a wurtzite structure. The field emission
      properties of the GaN-filled carbon nanotubes have been achieved with high and
      stable emission current. It is attributed to the unique cable-like structure,
      which makes the GaN-core/C-shell composite mechanically solid and chemically
      stable. This study suggests the GaN-filled carbon nanotube as an ideal candidate
      for future high-current and high-power field emitter applications.

PMID- 17450881
TI  - Modulation of structural and electronic properties of fullerene and
      metallofullerenes by surface chemical modifications.
AB  - Many applications of fullerene, metallofullerene, and carbon nanotubes request
      the chemical modifications. But how the modification influences the stability,
      structural, and electronic properties that directly relate to the practical
      functions of the carbon nanomaterials, this issue is discussed in this paper. The
      outer chemical modifications can sensitively influence the stability of final
      derivatives of fullerenes, depending on parameters such as the number of the
      modified groups, the unintended impurity groups on the cage surface, and chemical
      conditions in synthesizing processes. The outer chemical modification can induce
      alteration in electronic properties of metallofullerene. Gd@C82 is taken as a
      model to show how the electronic properties of the encaged metal atom are
      modulated by the cage surface modification. There exist sandwich-type electronic
      interactions along pathway: [outer modification group]-[cage surface]-[inner
      atom], and their synergistic effects are discussed. Beside the number of the
      modified groups, whose distribution patterns on the cage surface also play
      crucial roles in determining how the electronic interactions are modulated. Their
      synergistic effects dominate the electronic, optical, or magnetic properties of
      functionalized fullerenic nanomaterials. As the surface of nanotube is chemically
      more inert as compared to that of fullerene or metallofullerene, to achieve
      desirable modulations of nanotubes is probably more difficult. The research aimed
      to explore the changes in their structural or electronic property after the outer
      chemical functionalization was few, though this is of special significant and
      needs investigations because the chemical modifications are widely applying to
      the carbon nanotubes in applications.

PMID- 17450882
TI  - Modeling the structure of fulleranes and their endohedral complexes involving
      small molecules with nontrivial topological properties.
AB  - 'In' and 'out' isomers of perhydrogenated fullerenes and endohedral fullerene
      complexes have only recently been incorporated into the realm of topological
      chemistry. The 'in' isomers are, until now, purely hypothetical while for the
      latter group mostly studied are the complexes with metal ions that can be
      obtained during the fullerenes manufacturing. Much more difficult to obtain are
      the complexes with small molecules buried inside fullerene cages produced by
      laborious synthesis involving opening the cage, inserting the guest into it, and
      closing the cage chemically. This complicated procedure has only recently been
      accomplished for a hydrogen molecule put in the C60. Two H2 molecules inside the
      opened C70 cage and H2O in the opened C60 have been also reported recently. Model
      calculations, when carefully applied, allow one to predict the possibility of
      obtaining endohedral fullerene complexes with small molecules and 'in' isomers of
      perhydrogenated fullerenes. However, such systems are too large to be reliably
      handled by quantum calculations. Interestingly, such a simple method as molecular
      mechanics seems much more trustworthy.

PMID- 17450883
TI  - Structure and dynamics in self-organized C60 fullerenes.
AB  - This manuscript on 'structure and dynamics in self-organized C60 fullerenes' has
      three sections dealing with: (A) pristine C60 aggregate structure and geometry in
      solvents of varying dielectric constant. Here, using positronium (Ps) as a
      fundamental probe which maps changes in the local electron density of the
      microenvironment, the onset concentration for stable C60 aggregate formation and
      its phase behavior is deduced from the specific interactions of the Ps atom with
      the surrounding. (B) A novel methanofullerene dyad, based on a hydrophobic
      (acceptor C60 moiety)-hydrophilic (bridge with benzene and ester functionalities)
      hydrophobic (donor didodecyloxybenzene) network is chosen for investigation of
      characteristic self-assembly it undergoes leading to supramolecular aggregates.
      The pi-electronic amphiphile, necessitating a critical dielectric constant
      epsilon > or = 30 in binary THF-water mixtures, dictated the formation of bilayer
      vesicles as precursors for spherical fractal aggregates upon complete dyad
      extraction into a more polar water phase. (C) While the molecular orientation is
      dependent on the packing density, the ordering of the molecular arrangement,
      indispensable for self-assembly depends on the balance between the structures
      demanded by inter-molecular and molecule-substrate interactions. The molecular
      orientation in a monolayer affects the orientation in a multilayer, formed on the
      monolayer, suggesting the possibility of the latter to act as a template for
      controlling the structure of the three dimensionally grown self-assembled
      molecular aggregation. A systematic study on the electronic structure and
      orientation associated with C60 functionalized aminothiol self-assembled
      monolayers on Au(111) surface is presented using surface sensitive Ultra-Violet
      Photoelectron Spectroscopy (UPS) and C-K edge Near-Edge X-ray Absorption Fine
      Structure (NEXAFS) spectroscopy. The results revealed drastic modifications to d
      band structure of Au(111) and the electronic structure was found sensitive
      towards the S-Au interface and the C60 end functional moiety with formation of
      localized sigma-(S-Au) and sigma(N-C) bonds, respectively. Upon binding C60 to
      the amine-terminated alkanethiol SAM, a drastically reduced HOMO-LUMO gap of 2.7
      eV as compared to a large electronic gap of approximately 8 eV in alkanethiols
      enables the SAM to be a potential electron transport medium.

PMID- 17450884
TI  - Ferromagnetism in C60 polymers: pure carbon or contamination with metallic
      impurities?
AB  - A review of ferromagnetism in C60 polymeric materials synthesized by high
      pressure high temperature (HPHT) treatment is presented. Analysis of published
      data proves that the reported ferromagnetism cannot be assigned to polymeric
      structure in either perfect or defect states. Most recent experimental studies
      have not confirmed previously reported levels of magnetization in polymeric
      samples while it appears that ferromagnetism of "magnetic carbon" is preserved
      above the depolymerization point of any C60 polymer. Identical ferromagnetic
      properties in some samples of fullerene polymer and graphite like hard carbon
      phase also show that the effect is most likely not connected to fullerenes at
      all. Most of the data published previously as an evidence of ferromagnetism in
      C60 polymers synthesized at HPHT conditions can be explained by contamination
      with magnetic impurities. Formation of iron carbide (Fe3C) due to reaction of
      metallic iron with fullerene molecules allows to explain observed Curie
      temperature of approximately 500 K and levels of magnetization reported for
      "magnetic carbon".

PMID- 17450885
TI  - Radical reactions of [60]fullerene mediated by manganese(III) acetate dihydrate.
AB  - Mn(OAc)3 x 2H2O is an excellent reagent to promote free radical reactions of C60.
      C60 reacted with various methylene active compounds, methyl ketones, beta-enamino
      carbonyl compounds, carboxylic acid derivatives, and diallylamines in the
      presence of Mn(OAc)3 x 2H2O to afford singly-bonded fullerene dimers, 1,4
      bisadducts and 1,16-bisadducts of C60, C60-fused dihydrofuran derivatives,
      methanofullerenes, C60-fused pyrroline derivatives, C60-fused lactone
      derivatives, and C60-fused pyrrolidine derivatives. Mn(OAc)3 x 2H2O was
      successfully employed to transform ArC60-H into ArC60-OAc.

PMID- 17450886
TI  - Fullerene containing polymers: a review on their synthesis and supramolecular
      behavior in solution.
AB  - Due to the theoretical importance and potential applications of fullerene,
      numerous fullerene derivatives have been developed to enhance its solubility and
      processability. This article provides an overview on fullerene containing
      polymers, from synthesis to their physicochemical properties in solution. Due to
      the unique chemical structure of fullerene, different fullerene containing
      polymeric architecture can be synthesized through various kinds of conjugating
      techniques, where fullerene can be located either on the backbone or the branch
      chain. Recently, the successful development of azido coupling and atom transfer
      radical addition (ATRA) makes it possible to synthesize "controlled" and well
      defined fullerene containing polymers. Experimental results indicated that
      fullerene containing polymers not only increase the solubility of fullerene in
      solution, but also retain the conjugating properties of fullerene molecules. By
      blocking well-defined functional polymers onto fullerene molecules, different
      types of stimuli-responsive amphiphilic systems can be achieved. However, the
      large bulk volume and high hydrophobicity of fullerene gives rise to the large
      aggregates with different morphologies produced in solution, which can be tuned
      by changing external stimuli, such as pH, temperature, salt, and co-solvents.
      Interestingly, fullerene containing anionic polymers could induce the formation
      nano-scale fractal pattern, but not fullerene containing cationic polymers, which
      is evident from morphological studies.

PMID- 17450887
TI  - Studying single-wall carbon nanotubes through encapsulation: from optical methods
      till magnetic resonance.
AB  - Encapsulating fullerenes, magnetic fullerenes, 13C isotope enriched fullerenes,
      and organic solvents inside SWCNTs enables to yield unprecedented insight into
      their electronic, optical, and interfacial properties and to study SWCNT growth.
      In addition to customary methods of their studies such as e.g., optical
      absorption or Raman spectroscopy, these efforts enables to employ electron spin
      resonance (ESR) and nuclear magnetic resonance (NMR) spectroscopy. Encapsulated
      C60 fullerenes are transformed to inner tubes by a high temperature annealing.
      The diameter distribution of the inner tubes follow that of the outer ones and
      their unique, low defect concentration makes them an ideal model system for high
      resolution and energy dependent Raman studies. The observation of Raman modes of
      individual inner-outer tube pairs allows to measure the inner-outer tube
      interaction strength that is also well described theoretically. Reversible
      closing and opening of SWCNT can be studied in a diameter selective manner by
      encapsulating C60 and transforming it to an inner tube. The growth of inner tubes
      can be achieved from 13C enriched encapsulated organic solvents, which shows that
      the geometry of the fullerene does not play a particular role in the inner tube
      growth as it was originally thought. In addition, it opens new perspectives to
      explore the in-the-tube chemistry. Growth of inner tubes from 13C enriched
      fullerenes provides a unique isotope engineered heteronuclear system, where the
      outer tubes contain natural carbon and the inner walls are controllably 13C
      isotope enriched. The material enables to identify the vibrational modes of inner
      tubes which otherwise strongly overlap with the outer tube modes. The 13C NMR
      signal of the material has an unprecedented specificity for the small diameter
      SWCNTs. Temperature and field dependent 13C T1 studies show a uniform metallic
      like electronic state for all inner tubes rather than distributed metallic and
      isolating behavior. A low energy, 3 meV gap is observed that is tentatively
      assigned to a long sought Peierls transition in the small diameter SWCNTs.
      Encapsulating magnetic fullerenes, such as N@C60 and C59N opens the way for local
      probe ESR studies of the electronic properties of the SWCNTs.

PMID- 17450888
TI  - Hole-doping of fullerenes and nanotubes by way of intercalation chemistry.
AB  - Succeeding to the electron-doping processes of carbon nanostructures, chemical
      methods devoted to the hole-doping of the latter have significantly developed
      over the past ten years. Intercalation chemistry remains a top-rated technique in
      this purpose, among the variety of available chemical doping schemes. A review of
      the p-type doping of fullerenes and nanotubes by this method is exposed, which
      also includes a wide range of derived potential applications and prospects
      regarding the materials thus obtained.

PMID- 17450889
TI  - Electrical properties and applications of carbon nanotube structures.
AB  - The experimentally verified electrical properties of carbon nanotube structures
      and manifestations in related phenomena such as thermoelectricity,
      superconductivity, electroluminescence, and photoconductivity are reviewed. The
      possibility of using naturally formed complex nanotube morphologies, such as Y
      junctions, for new device architectures are then considered. Technological
      applications of the electrical properties of nanotube derived structures in
      transistor applications, high frequency nanoelectronics, field emission, and
      biological sensing are then outlined. The review concludes with an outlook on the
      technological potential of nanotubes and the need for new device architectures
      for nanotube systems integration.

PMID- 17450890
TI  - Carbon nanotube-based functional materials for optical limiting.
AB  - Optical limiting is an important application of nonlinear optics, useful for the
      protection of human eyes, optical elements, and optical sensors from intense
      laser pulses. An optical limiter is such a device that strongly attenuates high
      intensity light and potentially damaging light such as focused laser beams,
      whilst allowing for the high transmission of ambient light. Optical limiting
      properties of carbon nanotube suspensions, solubilized carbon nanotubes, small
      molecules doped carbon nanotubes and polymer/carbon nanotube composites have been
      reviewed. The optical limiting responses of carbon nanotube suspensions are shown
      to be dominated by nonlinear scattering as a result of thermally induced solvent
      bubble formation and sublimation of the nanotubes, while the solubilized carbon
      nanotubes optically limit through nonlinear absorption mechanism and exhibit
      significant solution-concentration-dependent optical limiting responses. In the
      former case the optical limiting results are independent of nanotube
      concentrations at the same linear transmittance as that of the solubilized
      systems. Many efforts have been invested into the research of polymer/carbon
      nanotube composites in an attempt to allow for the fabrication of films required
      for the use of nanotubes in a real optical limiting application. The higher
      carbon nanotube content samples block the incident light more effectively at
      higher incident energy densities or intensities. The optical limiting mechanism
      of these composite materials is quite complicated. Besides nonlinear scattering
      contribution to the optical limiting, there may also be other contributions e.g.,
      nonlinear absorption, nonlinear refraction, electronic absorption and others to
      the optical limiting. Further improvements in the optical limiting efficiency of
      the composites and in the dispersion and alignment properties of carbon nanotubes
      in the polymer matrix could be realized by variation of both nanostructured guest
      and polymer host, and by ex situ alignment and other methods. It would be very
      desirable, from the practical application point of view, if one can design
      broadband optical limiting chromophores that would function in a multimechanistic
      fashion.

PMID- 17450891
TI  - Biological properties of carbon nanotubes.
AB  - Carbon nanotubes are novel materials with unique physical and chemical
      properties, and have been considered for use in numerous technological
      applications. More recently, attention has turned to the unique biological and
      medical properties of these materials. In this review, the processing, chemical
      properties, physical properties, nucleic acid interaction, cell interaction, and
      toxicologic properties of nanotubes are described. Finally, future directions in
      this area are discussed.

PMID- 17450892
TI  - Advances and prospects on biomolecules functionalized carbon nanotubes.
AB  - In recent years, functionalization of carbon nanotubes (CNTs) with biomolecules
      such as nucleotide acids, proteins, and polymers as well as cells have emerged as
      a new exciting field. Theoretical and experimental studies of structure and
      function of bio-inspired CNT composites have made great advances. The importance
      of nucleic acids, proteins, and polymers to the fundamental developments in CNT
      based bio-nano-composites or devices has been recognized. In particular,
      biomechanics, biochemistry, thermodynamics, electronic, optical, and magnetic
      properties of the bio-inspired CNT composites have become a new interdisciplinary
      frontier in life science and nanomaterial science. Here we review some of the
      main advances in this field over the past few years, explore the application
      prospects, and discuss the issues, approaches, and challenges, with the aim of
      stimulating a broader interest in developing CNT-based bio-nanotechnology.

PMID- 17450893
TI  - Influence of buffer gas and vibration temperature of carbon clusters on fullerene
      formation in a carbon plasma.
AB  - A new model for calculation of fullerene formation rate in carbon containing
      plasma is proposed. The model takes into account carbon cluster heating and
      cooling during transformations due to chemical bonds formation and destruction.
      In addition, the heating and cooling of carbon clusters by buffer gas is
      considered. The calculations give the qualitatively correct correlation between
      fullerene yields in helium and argon.

PMID- 17450894
TI  - Kekule structure count in corazulenic fullerenes.
AB  - Tiling modification in fullerene modeling can be achieved by some map operations.
      In this respect, sequences of classical operations, or single generalized
      operations, were used to obtain corannulene-like azulenic patterns. The
      aromaticity of such cages tessellated by "corazulenic" supra-faces is discussed
      in terms of several criteria. Particularly, the number of Kekule valence
      structures, was considered as a rough measure of the fullerene aromaticity and
      implicitely of their stability. The covering was given as a pi-electron partition
      within some Kekule valence structures. The well-known geometric index of
      aromaticity HOMA (harmonic oscillator model of aromaticity) enabled the
      evaluation of local aromaticity of the discussed supra-faces and brought evidence
      for several dominant Kekule valence structures.

PMID- 17450895
TI  - Structural patterns in fullerenes showing adjacent pentagons: C20 to C72.
AB  - We have analyzed in detail the structure of the smallest fullerenes C(n) (20 < or
      = n < or = 72) obtained in B3LYP/6-31G* calculations. All these systems, except
      for C60, C70, and C72, necessarily present adjacent pentagons in their structure.
      For the most stable classical isomers, we have studied the variation of bond
      distances, HOMO-LUMO gaps and enthalpies of formation with fullerene size. A
      classification of the bonds in 9 different motifs permits to gain insight in the
      factors determining the fullerene stability. A simplified model that assumes a
      fixed energy per bond is able to reproduce the calculated enthalpies of formation
      and to estimate the energy change associated with each structural motif. An extra
      stabilization of 30-40 kcal/mol is predicted for the fullerenes showing spherical
      aromaticity.

PMID- 17450896
TI  - Calculations on endohedral C74 complexes.
AB  - While empty C74 is still a rather elusive fullerene, its endohedral derivatives
      are well established. The report surveys computations for three of C74-based
      endohedrals--Ca@C74, Ba@C74, and Yb@C74. A set of six C74 cages is considered,
      namely one cage with isolated pentagons, three isomers with a pentagon-pentagon
      junction, two structures with one pair of connected pentagons, and one heptagon.
      Special interest is paid to the Gibbs-energy evaluations for estimations of the
      relative populations.

PMID- 17450897
TI  - Structures and electronic properties of M2C2 @ C78 (M = Ti, Zr, Hf): a density
      functional theory study.
AB  - A systematic DFT investigation has been conducted to explore the structures and
      electronic properties of the metal-carbide endofullerenes M2C2 @ C78 (M = Ti, Zr,
      Hf) at the PBE/DNP level of theory. The theoretical calculations predicted the
      following: (i) this series of endofullerenes have the valence states [M4+]2C2(2-)
      @ C78(6-) (ii) the structure of the [M2C2](6+) cluster encapsulated in the C78(6
      ) (D3h) cage varies with the increasing of the ionic radius of M4+, i.e., from a
      linear M-C [triple bond] C-M geometry for M = Ti, through a zigzag geometry for M
      = Hf to a side-on binding mode for M = Zr; (iii) M2C2 @ C78 (M = Zr, Hf) should
      display interesting intramolecular dynamic behavior at room temperature, i.e.,
      the encapsulated C2(2-) moiety can rotate freely around the C3-axis of the C78(6
      ) (D3h) cage; (iv) the [Ti2C2]6+ in the lightest Ti2C2 @ C78 is far more fixed by
      adopting the linear Ti-C - C-Ti geometry; (v) the order for their ionization
      potentials is Ti2C2 @ C78 < Hf2C2 @ C78 << Zr2C2 @ C78, whereas their EAs follow
      the order: Ti2C2 @ C78 < Hf2C2 @ C78 approximately Zr2C2 @ C78. The predicted
      redox properties of these endofullerenes suggest that Zr2C2 @ C78 is
      synthetically as approachable as Hf2C2 @ C78.

PMID- 17450898
TI  - Comparative investigation of derivatives of C60 and its isomers.
AB  - To provide insight into the derivatization of fullerenes, extensive density
      functional theory calculations were performed on their hydrides and fluorides of
      several isomers of C60. The calculated results demonstrate that the hydrides and
      fluorides of isolated pentagon rule (IPR) C60 are less stable than those of non
      IPR C60. These results indicate that derivatization may cause structural
      transformation of a fullerene; and that many more non-IPR fullerenes may be
      captured in the forms of derivatives.

PMID- 17450899
TI  - Comparative process analysis of fullerene production by the arc and the radio
      frequency discharge methods.
AB  - In this work, comparative analysis of processes in carbon arc and radio frequency
      (RF) plasma during fullerene synthesis has been presented. The kinetic model of
      fullerene formation developed earlier has been verified in both types of plasma
      reactors. The fullerene yield depended on carbon concentration, velocity of
      plasma flame and rotational temperature of C2 radicals predominantly. When mean
      rotational temperature of C2 radicals was 3000 K, the fullerene yield was the
      highest regardless of the type of used reactor. The zone of fullerene formation
      is larger significantly in RF plasma reactor compared to arc reactor.

PMID- 17450900
TI  - Nanocrystalline diamond thin films deposited from C60 monoenergetic fullerene ion
      beam.
AB  - Carbon films 250 division by 500 nm in thickness deposited on Si wafers from mass
      selected flow of accelerated C60 ions with energies of 5.0 +/- 0.1 keV at
      temperatures of 300 K and 673 K are characterized by TEM and nanoindentation. On
      the TEM images of the films deposited at 673 K, nanocrystalline graphite with the
      typical grain size of -6 nm is observed. The films deposited at 300 K are
      transparent in visible light. TEM study of these films has revealed structural
      elements with lattice spacing close to that of diamond and the grain size of
      about 4 nm. Nanohardness and elastic modulus of the films prepared at a substrate
      temperature of 300 K were 23.1 +/- 0.2 GPa and 200 +/- 1 GPa, respectively.
      Possible mechanisms of the carbon films structure formation are suggested in the
      framework of a hydrodynamic shock wave model.

PMID- 17450901
TI  - Synthesis of allyl-bearing dendrimers with a resorcinarene core and their
      supramolecular complexes with fullerene C60.
AB  - Dendritic branches of poly(arylether) with peripherial allyl chains have been
      attached to a resorcinarene core. Dendrimers of first, second, and third
      generation were synthesized. Viability to form supramolecular complexes with
      fullerene C60 was studied with three dendrimers of first, second, and third
      generation. All the compounds were characterized by 1H, 13C NMR, FTIR, UV-vis
      spectroscopy, MALDI-TOF, FAB+ mass spectra, and elemental analysis. Strong pi-pi,
      CH-pi, and n-pi interactions between the dendrimers and the fullerene C60 were
      detected in the supramolecular complexes by UV-vis, FTIR, and 13C CP-MAS NMR.

PMID- 17450902
TI  - Complexation of higher fullerenes by calix[5]arene-based host molecules.
AB  - The binding abilities of calix[5]arene-based host molecules for higher fullerenes
      (C76, C78, and C84) were investigated in organic solvents. The binding abilities
      of double-calix[5]arenes to higher fullerenes are high. In particular, their
      association constants to C76 and C78 in toluene reached at the order of 10(5) M(
      1). In contrast, the binding abilities of simple calix[5]arenes decreased as
      increasing the size of the fullerenes. Accordingly, linking two calix[5]arenes
      with the covalent bonds creates the large cavities, complementary to higher
      fullerenes. The structure of the host-guest complex of double-calix[5]arene and
      C76 was discussed. The carbons of the polar end of C76 characteristically shifted
      upfield more than the other carbons in the host-guest complex, indicating that
      these polar carbons reside most deeply inside the cavity of the calix[5]arene.

PMID- 17450903
TI  - Can apomyoglobin form a complex with a spherical ligand? Interactions between
      apomyoglobin and [C60] fullerene derivative.
AB  - The preparation and characterization of the stable equine skeletal muscle
      apomyoglobin and eee-isomer of tris-malonic acid [C60] fullerene complex is
      reported. For this new bio-nanomaterial preparation, a procedure of complexation
      during-protein-refolding was used and the obtained compound sustained separation
      by gel-filtration and ion-exchange chromatography. The apomyoglobin-tris-malonic
      acid [C60] fullerene complex was characterized by UV-vis spectroscopy, steady
      state fluorescence, time-resolved fluorescence, and circular dichroism
      spectroscopies. Important information provided by this study, regarding the
      stability and properties of new material, may lead to a better understanding of
      the apomyoglobin protein binding characteristics, as well as to development of
      novel antioxidant and photodynamic therapeutic agents and components for
      bioelectronic devices.

PMID- 17450904
TI  - Synthesis, characterization, and electrochemical properties of mono-, di-, and
      trinuclear transition Metal [60]fullerene complexes containing diphosphine cis
      Ph2PCH=CHPPh2 ligand.
AB  - New transition metal fullerene complexes containing cis-Ph2PCH=CHPPh2 (dppet)
      ligand have been investigated. The mononuclear complexes (etau2-C60)M(cis-dppet)
      (1, 2; M = Pd, Pt) were prepared by reaction of C60 with M(dba)2 (dba =
      dibenzylideneacetone) followed by treatment with cis-dppet, while the in situ
      prepared 1 and 2 reacted with M1(PPh3)4 to afford dinuclear complexes (eta2 :
      eta2-C60)M(cis-dppet)M1 (PPh3)2 (3-6; M, M1 = Pd, Pt). Similarly, trinuclear
      complexes (eta2 : eta2-C60) M(cis-dppet)M1 (dppr) (7-10; M, M1 = Pd, Pt; dppr =
      (eta5-Ph2PC5H4)2Ru) could be synthesized by reaction of the in situ prepared 3-6
      with dppr. 1-10 were characterized by elemental analysis and spectroscopy. Cyclic
      voltammetric studies on 2 (M = Pt), 3 (M = Pd, M1 = Pd) and 9 (M = Pt, M1 = Pd)
      provided further evidence for the eta2-coordination of C60 to one metal fragment
      or two metal fragments in these complexes.

PMID- 17450905
TI  - AFM analysis of C60 and a poly(amido amine) dendrimer-C60 nanoconjugate.
AB  - Atomic force microscopy (AFM) was used to study the nanoscopic structure and
      topography of buckminsterfullerene (C60) and a conjugate of C60 with generation
      four, amine-terminated, poly(amido amine) dendrimer (PAMAM-G4). The conjugate
      contains a PAMAM-G4 core and C60 shell formed by reacting PAMAM-G4 with an excess
      of C60. Fractal patterns of C60 were observed in nanoscopic AFM images when
      solutions of different concentrations of C60 in pyridine or toluene were dried at
      room temperature. In contrast, no fractal patterns were detected in the AFM
      images of the dendrimer-C60 nanoconjugate, prepared from pyridine solution in a
      similar manner. Thus, the C60-shell alone is not sufficient to impart the same
      fractal patterns on the conjugate.

PMID- 17450906
TI  - Neutron and X-ray scattering on the monolayer structure of a lecithin fullerene
      derivative.
AB  - Using neutron reflectivity with contrast variation, X-ray reflectivity, and
      grazing incident small-angle X-ray scattering (GISAXS), we have characterized the
      in-depth and in-plane structural characteristics of the Langmuir and Langmuir
      Blodgett (LB) films formed by a novel lecithin C60-derivative, FPTL, of three
      phospholipids jointly bonded on one single olefinic moiety of a C60 cage. Based
      on the neutron reflectivity measured, we have proposed a monolayer structure,
      with the C60 cages of FPTL lifted into the air and hydrophilic phospholipid heads
      immersed in water, for the FPTL Langmuir layer formed on water. On the other
      hand, the LB film of FPTL prepared on mica exhibits clear Kiessig fringes in the
      X-ray reflectivity profile, indicating a 27 angstroms monolayer film with less
      molecular orientation. With GISAXS, we have extracted an in-plane correlation
      length of about 210 A for a possible in-plane aggregation of C60 of FPTL in the
      LB monolayer. We have also demonstrated the highly ordered monolayer structures
      of a lecithin lipid, in elucidating the positive effect of the attached
      functional group-phospholipids on the monolayer formation of the lecithin C60
      derivative.

PMID- 17450907
TI  - Phototransformation of C60 thin films by UV pulsed laser irradiation: comparative
      photoacoustic, AFM, and Raman studies.
AB  - Fullerene C60 films deposited by sublimation were irradiated with Kr-F laser in a
      wide fluence interval from 15 to 40 mJ/cm2. In situ photoacoustic analysis was
      applied to study the phase transformation during the irradiation. The results
      obtained were discussed in conjunction with atomic force microscopy (AFM) and
      Raman spectroscopy data. It was found that for a irradiation fluence interval
      from 22 to 30 mJ/cm2, 80% of C60 undergoes photopolymerization (presumably
      through 2 + 2 cycloaddition). For a laser energy higher than 30 mJ/cm2, a new
      amorphous carbon phase forms, having a large content of diamond-like, tetra
      amorphous carbon (ta-C).

PMID- 17450908
TI  - Photoinduced electron transfer and hole migration along copolymer of
      vinylbenzenepyrrolidinofullerene[60] and N-vinylcarbazole.
AB  - Photoinduced electron-transfer and hole-migration processes for newly prepared
      copolymers of C60 and N-vinylcarbazole (VCz) with the several compositions have
      been investigated using time-resolved fluorescence and absorption methods.
      Shortening of fluorescence lifetime of the C60 moiety in PVCz-C60 was observed,
      suggesting that the charge-separation takes place via the excited singlet state
      of C60; the rate constants of the charge-separation were evaluated to be larger
      than 10(9) S(-1) in polar solvents. In the nanosecond transient absorption
      spectra in the visible and near-IR regions obtained by excitation of the C60
      moiety, the generation of PVCz(*+)-C60(*-) was confirmed. The time profiles of
      these radical ions showed slow decay continuing more than 800 micros in polar
      solvents. From the simulations of the decay curves on the basis of the proposed
      kinetic model, in which the charge-recombination takes place competitively with
      hole-migration, the rate parameters have been evaluated; i.e., the rate constant
      of hole migration was evaluated to be 5 x 10(7) s(-1), which was 50 times faster
      than that of the charge-recombination (ca. 10(6) s(-1)) in polar solvent. The
      charge-recombination takes place after hole migration among 200-300 Cz units
      along the PVCz chain in PVCz-C60.

PMID- 17450909
TI  - Electronic spectra of the crystalline polymers of C60: photoluminescence study at
      high pressure.
AB  - Specific details of the electronic spectra of perfect crystalline polymers of C60
      were studied by means of the photoluminescence spectra measurements at normal
      conditions and at high pressure up to 4 GPa. The structure of the
      photoluminescence spectra, the intensity distribution between the principal bands
      and the pressure-induced shift of the bands differ considerably among the
      pristine C60, linear orthorhombic and planar tetragonal and rhombohedral
      polymeric phases of C60. Unlike the planar polymers of C60, the linear
      orthorhombic polymer exhibits irreversible changes in the photoluminescence
      spectrum under simultaneous application of high pressure and laser irradiation.
      The changes observed in the photoluminescence spectra of the planar polymeric
      phases of C60, as compared to the pristine material, are discussed in relation to
      the corresponding changes in the calculated electronic structure of the pristine
      C60 and its polymeric phases. The observed photoluminescence spectral structure
      along with the pressure behavior of the photoluminescence spectra are very
      sensitive to the structure of the polymers as well as to the C60 cage
      deformations and can be used to effectively characterize the various polymeric
      phases of C60.

PMID- 17450910
TI  - Conductance and polarisability of C60 films.
AB  - Thin films of C60 deposited in vacuum are studied using current-voltage (I-V)
      measurements and atomic force microscopy (AFM). In situ electrical measurements
      give an average resistivity of ca. 30 Mn cm for the as-deposited films at room
      temperature. The I-V dependences are found to correspond to ohmic behaviour but
      they have a hysteresis shape attributed to remnant polarisation due to the domain
      structure of the films. AFM images show a grainy surface morphology for the
      deposited C60. Temperature dependent measurements in the range 290-365 K provide
      evidence for a variable range hopping mechanism of conductance with an activation
      energy of 0.8-1.0 eV. With further temperature increase the C60 films restructure
      leading to an increase in grain size and a change of the electrical properties
      with I-V dependences showing Schottky barrier formation. The effect of oxygen on
      the conductance of the C60 films under their exposure to an ambient atmosphere is
      considered and discussed.

PMID- 17450911
TI  - Ozone reaction with carbon nanostructures. 1: Reaction between solid C60 and C70
      fullerenes and ozone.
AB  - The exposure of powdered crystals of C60 and C70 fullerenes to ozone with an
      O3/O2 ratio of 9.7% w/w causes their immediate oxidation. The FT-IR spectroscopy
      shows the formation of CO2 and the accelerated disappearance of ozone. The
      infrared spectra of crystalline C60 and C70 powders that were exposed to ozone
      show absorption bands indicating that oxidation was accompanied by formation of
      alpha,beta-unsaturated carboxylic groups, aldehyde and other ketonic moieties.
      The spontaneous decay of O3 in the O3/O2 atmosphere monitored by FT-IR
      spectroscopy was found to follow a pseudofirst order kinetic law with k0 = 6.9 x
      10(-5) s(-1). When powdered C60 is present in the system a k(C60)(1) = 2.0 x 10(
      4) s(-1); k(C70)(1) = 1.4 x 10(-4) s(-1) for C70. The accelerated disappearance
      of O3 is due to its adsorption/reaction with the powdered fullerenes. After about
      approximately 1000 s the reaction enters in a second step wherein the
      disappearance of O3 slows down significantly due to the lack of further reaction
      sites on the powdered fullerene surfaces and due to accumulated CO2 in the gas
      phase which exerts an inhibitory effect in the ozone spontaneous decomposition.

PMID- 17450912
TI  - Ozone reaction with carbon nanostructures. 2: The reaction of ozone with milled
      graphite and different carbon black grades.
AB  - Synthetic graphite particles 0.2 microns in diameter react with O3 at room
      temperature with evolution of CO2. Graphite is less reactive with ozone than
      carbon blacks having different surface area ranging from 120 to 8 m2/g, but
      graphite reactivity is comparable to that shown by powdered solid C60 and C70
      fullerenes. The kinetic rate constant derived from the ozone consumption k
      appears in relation with the rate of CO2 evolution suggesting a very simple
      reaction stoichiometry at the early stages. The reaction between ozone and
      graphite or carbon blacks essentially involves two stages: the gasification of
      the surface to CO2 and its functionalization with oxygenated chemical groups,
      mainly as COOH but also other oxygenated chemical moieties. The pseudofirst order
      kinetics appears adequate to describe the heterogeneous reaction between ozone
      and the selected carbon materials. The discussion of the results is focused on
      the role played by fullerene-like carbon nanostructures, present in graphene
      sheets to explain the observed gasification rates and surface functionalization.

PMID- 17450913
TI  - Self assembling of porphyrin-fullerene dyads in the Langmuir and Langmuir
      Blodgett films: formation as well as spectral, electrochemical and vectorial
      electron transfer studies.
AB  - Donor-acceptor dyads of water-soluble Zn porphyrins and C60 bearing either
      pyridine or imidazole ligand were self assembled via axial coordination in
      Langmuir and Langmuir-Blodgett (LB) films. Compression and surface potential
      versus area per molecule isotherms as well as ellipsometry and BAM measurements
      showed that molecules were aggregated in all Langmuir films before compression.
      The area per molecule in the absence of aggregation was determined by linear
      extrapolation of the area at the zero surface pressure to infinite adduct
      dilution. Comparison of the extrapolated and theoretically calculated areas,
      being dependent on the composition of the subphase solution, indicated that dyads
      were oriented with their porphyrin macrocycles in plane of the air-solution
      interface. Calculated by molecular modeling thickness of the Langmuir films was
      in accord with that determined by ellipsometry. The Langmuir films were
      transferred, by using the LB technique, onto different solid substrates for
      spectroscopic, microscopic, electroanalytical, and photochemical
      characterization. From the IR spectroscopy investigations it followed that the
      porphyrin macrocycle of the dyad was either nearly parallel or tilted with
      respect to the substrate plane. Molecularly modeled pseudo-hexagonal packing and
      thickness of the LB films were in accord with that imaged by STM and determined
      by ellipsometry, respectively. The electrochemical redox states of the dyads were
      established by performing simultaneous cyclic voltammetry and piezoelectric
      microgravimetry measurements of the LB films on Au-quartz electrodes. Both steady
      state and time-resolved emission studies of the zinc porphyrin-fullerene LB films
      revealed efficient quenching of the singlet-excited Zn porphyrin. Based on the
      free-energy calculations and dyad orientation in the film, this quenching was
      attributed to vectorial electron transfer within the dyad.

PMID- 17450914
TI  - A novel building block for donor-acceptor conjugated polymers containing
      perylene, poly(p-phenylenevinylene), and fullerene.
AB  - A series of new polymers containing perylene, poly(p-phenylenevinylene) (PPV)
      and/or pendant fullerene units have been synthesized by Wittig condensation. All
      of the polymers were characterized by 1HNMR, FT-IR, and GPC. The optical
      properties of the polymers were studied by UV-vis and FL spectra. The cyclic
      voltammetry showed us a good candidate for a photoinduced electron-transfer
      system. And the photocurrent measurement revealed an interesting phenomenon that
      the photocurrent increased with the contents of the fullerene in the polymers
      increased.

PMID- 17450915
TI  - Effects of hydrated forms of C60 fullerene on amyloid 1-peptide fibrillization in
      vitro and performance of the cognitive task.
AB  - It has been shown for the first time by transmission electron microscopy that the
      hydrated fullerene C60 inhibited the fibrillization of amyloid-beta25-35 peptide.
      The fullerene affected the amyloid-beta25-35 assembly, manifesting its anti
      amyloidogenic capacity. Our in vivo investigations demonstrated also that a
      single intracerebroventricular injection of the C60 hydrated fullerene at a dose
      of 7.2 nmol/ventricle significantly improved the performance of the cognitive
      task in control rats. The intracerebroventricular injection of the C60 hydrated
      fullerene (3.6 nmol/ventricle) prevented the impairment of performance of the
      cognitive task induced by amyloid-beta25-35 (22.5 nmol/ventricle). The results
      obtained may be useful in the development of therapy of Alzheimer's disease.

PMID- 17450916
TI  - Nanoporous hard carbon membranes for medical applications.
AB  - Current blood glucose sensors have proven to be inadequate for long term in vivo
      applications; membrane biofouling and inflammation play significant roles in
      sensor instability. An ideal biosensor membrane material must prevent protein
      adsorption and promote integration of the sensor with the surrounding tissue.
      Furthermore, biosensor membranes must be sufficiently thin and porous in order to
      allow the sensor to rapidly respond to fluctuations in analyte concentration. In
      this study, the use of diamondlike carbon-coated anodized aluminum oxide as a
      potential biosensor membrane is discussed. Diamondlike carbon films and
      diamondlike carbon-coated anodized aluminum oxide nanoporous membranes were
      examined using scanning electron microscopy, atomic force microscopy, X-ray
      photoelectron spectroscopy, Raman spectroscopy, and platelet rich plasma testing.
      The diamondlike carbon-coated anodized aluminum oxide membranes remained free
      from protein adsorption during in vitro platelet rich plasma testing. We
      anticipate that this novel membrane could find use in immunoisolation devices,
      pacemakers, kidney dialysis membranes, microdialysis systems, and other devices
      facing biocompatibility issues that limit in vivo function.

PMID- 17450917
TI  - A vapor-liquid-solid model for chemical vapor deposition growth of carbon
      nanotubes.
AB  - Although carbon nanotubes (CNTs) with a variety of morphologies have been
      successfully synthesized, there is no clear physical picture of the growth
      process. Correspondingly, the growth mechanism is still not clear up to now. Here
      we suggest a VLS model for the growth process of CNTs, which involves a liquid or
      liquid-like state catalyst. The basic idea is that, due to the high thermal
      conductivity and nanometer size of the catalyst and the fast diffusion of carbon
      atoms in it, both the temperature and the carbon atom distribution across it are
      uniform. The supersaturation level can be expressed as a function of the carbon
      concentration and temperature, which determines the nucleation dynamics and
      growth kinetics. Based on this model, the growth rate equation was obtained to
      describe the growth kinetics of carbon nanotubes, which shows good accordance
      with the experimental results.

PMID- 17450918
TI  - Application of molecular dynamics simulations for structural studies of carbon
      nanotubes.
AB  - Molecular dynamics studies based on the Brenner-Tersoff second-generation
      reactive empirical bond order potential and the Lennard-Jones carbon-carbon
      potential for intra- and inter-layer interactions have been performed for carbon
      nanotubes. These potentials reproduce reasonably the carbon-carbon distances and
      inter-layer spacing. The structure factors and the reduced radial distribution
      functions computed from the cartesian coordinates, resulting from energy
      minimisation and molecular dynamics simulations at 2 K and 300 K have been
      obtained for two models of two- and five-wall carbon nanotubes containing defects
      in the form of five and seven membered carbon rings. The results of computations
      have been compared with experimental data obtained from neutron and X-ray
      diffraction. The energy relaxation and the molecular dynamics simulations at 2 K
      and 300 K with appropriate values of the Debye-Waller factor lead practically to
      the same results which are in a good agreement with the experimental data
      indicating that molecular dynamics reproduce all structure features of the
      investigated carbon nanotubes together with thermal oscillations. Possible
      applications of this approach for other carbon nanotubes and related materials
      have been also discussed.

PMID- 17450919
TI  - The oscillatory characteristics of a 2C60/CNT oscillator system.
AB  - The authors have studied, using molecular dynamic (MD) simulations, the
      oscillatory characteristics of a 2C60/CNT oscillator system, in which two C60
      fullerenes oscillate inside a single walled carbon nanotube (CNT) in two basic
      modes, i.e., the symmetric and non-symmetric motions. In the symmetric mode, with
      each oscillation the two fullerenes move symmetrically from the CNT ends towards
      the CNT center where they bounce off each other and head back towards the ends.
      In the non-symmetric mode, the two fullerenes move back and forth inside the CNT
      crossing the center point of the CNT together with each oscillation. The
      simulations show that the non-symmetric oscillation mode is stable for the
      prescribed initial (maximum) velocities up to 300 m/s, while the symmetric
      oscillation mode however, experiences dynamic instabilities for a prescribed
      initial (maximum) velocity larger than 250 m/s. The instability takes place as a
      result of the transfer of energy from the translational to the rotational motion
      of the fullerenes. This characteristic differentiates 2C60/CNT oscillators from
      double-walled CNT oscillators. The rotation is primarily caused by the inter
      colliding of the two fullerenes, which subjects the fullerenes to large van der
      Waals repelling forces. These repelling forces are not necessarily aligned
      perfectly along the CNT axis nor precisely pointing towards the mass centers of
      the fullerenes. These misalignments cause the fullerenes to rock around the CNT's
      axis, while their offsets from the mass centers cause the fullerenes to rotate.
      The rocking motion, being severely confined by the CNT, does not gain much energy
      itself, but instead, channels energy from translational to rotational motion. The
      energy channeling is found to be reversed in some very short time intervals, but
      the rotational motion always gains energies from the translational motion over a
      time interval that is long enough at the MD time scale. This feature, contrary to
      our experiences in the macroscopic world, appears to be unique for such
      nanoscopic mechanical systems.

PMID- 17450920
TI  - Investigation of the influence of thermostat configurations on the mechanical
      properties of carbon nanotubes in molecular dynamics simulations.
AB  - The effect of thermostat configurations on the mechanical behavior of empty and
      butane (n-C4H10) filled (10, 10) carbon nanotubes (CNTs) is examined using
      classical, atomistic, molecular dynamics (MD) simulations. In particular, the
      influence of different types of thermostats, relative numbers of thermostat
      atoms, and rates of deformation are considered. The compressive forces on the
      atoms are calculated using the second generation reactive empirical bond-order
      potential. The results indicate that use of a Langevin thermostat leads to a
      substantial dependency of the results of CNT compression on the number of
      thermostat atoms and the rate of deformation. On the other hand, the Nose-Hoover
      and the velocity rescaling thermostats exhibit consistent mechanical responses
      during CNT compression regardless of the relative number of thermostat atoms.
      However, the Nose-Hoover thermostat fails to maintain the system temperature at a
      constant value during the compression process. Thus, this study indicates that
      the Langevin and velocity rescaling thermostats are more appropriate for use in
      classical MD simulations of CNT systems than the Nose-Hoover thermostat, and
      reveals the conditions under which these thermostats should be used for optimal
      consistency.

PMID- 17450921
TI  - Rapid acid-mediated purification of single-walled carbon nanotubes with
      homogenization of bulk properties.
AB  - A rapid, mild and readily scaleable method for purification and isolation of
      single-walled nanotubes (SWNTs) using aqueous nitric acid that, in only 1-2 hours
      at reflux temperature, not only decrease the content of residual metal particles
      but also the relative ratio of small diameter and metallic NTs. The acid-treated
      SWNTs have been characterised by TEM, FT-IR, and Raman spectroscopy (514 and 783
      cm(-1)). The results are discussed in relation to observations from other acid
      mediated treatments and the reactive chemical species involved at different
      conditions.

PMID- 17450922
TI  - Noncovalent functionalization of carbon nanotubes with porphyrins: meso
      tetraphenylporphine and its transition metal complexes.
AB  - Noncovalent functionalization of carbon nanotubes with meso-tetraphenylporphine
      (H2TPP) and its metal(II) complexes NiTPP and CoTPP was studied by means of
      different experimental techniques and theoretical calculations. As follows from
      the experimental adsorption curves, free H2TPP ligand exhibits the strongest
      adsorption of three porphyrins tested, followed by CoTPP and NiTPP. At the
      highest porphyrin concentrations studied, the adsorption at multi-walled carbon
      nanotubes was about 2% (by weight) for H2TPP, 1% for CoTPP, and 0.5% for NiTPP.
      Transmission electron microscopy observations revealed carbon nanotubes with a
      variable degree of surface coverage with porphyrin molecules. According to
      scanning electron microscopy, the nanotubes glue together rather than debundle;
      apparently, a large porphyrin excess resulting in polymolecular adsorption is
      essential for exfoliation/debundling of the nanotube ropes. The
      nanotube/porphyrins hybrids were studied by infrared and Raman spectroscopy, as
      well as by scanning tunneling microscopy. Electronic structure calculations were
      performed at the B3LYP/LANL2MB theoretical level with the unsubstituted porphine
      (H2P) and its Co(II) complex, on one hand, and open-end armchair (5,5) (ANT) and
      zigzag (8,0) (ZNT) SWNT models, on the other hand. The interaction of H2P with
      ANT was found to be by 3.9 kcal mol(-1) stronger than that of CoP. At the same
      time, CoP+ZNT complex is more stable by 42.7 kcal mol(-1) as compared to H2P+ZNT
      According to these calculated results, the free porphyrins interact less
      selectively with zigzag and armchair (i.e., semiconducting and metallic)
      nanotubes, whereas the difference becomes very large for the metal porphyrins.
      HOMO-LUMO structure, electrostatic potential and spin density distribution for
      the paramagnetic cobalt(II) complexes were analyzed.

PMID- 17450923
TI  - A nanohybrid material of SWNTs covalently functionalized with porphyrin for light
      harvesting antenna: synthesis and photophysical properties.
AB  - Novel covalently porphyrin functionalized single-walled carbon nanotubes (SWNTs)
      were synthesized using carboxylic group functionalized carbon nanotubes (o-SWNTs)
      with meso-aniline substituted porphyrin. The structure and morphology of this
      SWNT nanohybrid material were fully characterized with FTIR, Raman, UV-Vis-NIR
      spectra as well as TGA and TEM measurements. The energy transfer efficiency from
      porphyrin to SWNTs and porphyrin fluorescence quenching mechanism were studied by
      means of steady state fluorescence and time-resolved fluorescence measurement.
      The fast and efficient electron transfer occurring in this nanohybrid illustrates
      that they can be utilized as a good candidate for light harvesting materials in
      molecular photonic devices and solar energy utilization.

PMID- 17450924
TI  - Organometallic radical-adducts of fullerenes C60, C70, and single-walled carbon
      nanotubes derived from (cyclopentadienyl)molybdenumtricarbonyl dimer.
AB  - Interaction of the metal-centered free radicals [CpMo(CO)3]* generated
      photochemically from the corresponding dimer [CpMo(CO)3]2 with fullerenes C60,
      C70, or single-walled carbon nanotubes in toluene results in the radical-adducts
      investigated by using TGA, ESR, Raman and X-ray Photo-electron spectroscopy.
      Comparison was made with the chromium analogues previously studied.

PMID- 17450925
TI  - Functionalization of carbon nanotubes via dissolving metal reductions.
AB  - In this study we present direct sidewall functionalization of single-walled
      nanotubes, carried out via two different dissolving metal reduction methods. A
      modified Birch reduction scheme and a novel synthetic route were applied to form
      carbanion complexes on the surface of the nanotubes in liquid NH3 and
      tetrahydrofuran, respectively. The carbanion complex was reacted with a series of
      alkyl and aryl halogenides resulting in the corresponding SWNT derivatives. We
      determined the chemical composition and the thermal stability of the
      functionalized nanotubes by thermogravimetry/mass spectrometry and pyrolysis-gas
      chromatography. Characteristic decomposition peaks, observed in the temperature
      range of 350-600 degrees C, suggest the formation of covalent derivatives upon
      functionalization that is also supported by Raman spectroscopic studies. The
      influence of the functional groups and the type of nanotubes on the thermal
      stability, as well as the relationship between the functional group content and
      the intensity of the Raman D peak are discussed.

PMID- 17450926
TI  - Grafting reactions of living macroanions with multi-walled carbon nanotubes.
AB  - Grafting reactions of living polystyryllithium (PSLi) with acid chloride
      containing multi-walled carbon nanotubes (MWNTs-COCI) were performed under vacuum
      in benzene at room temperature. Covalent grafting of polystyrene (PS) was
      characterized using spectroscopic, microscopic, and thermogravimetric analyses.
      Grafting at different ratios of macroanion to acylchloride of the carbon
      nanotubes showed that the grafting efficiency was not dependent on the
      concentration of the macroanions. The mole percent of PS present in the MWNTs-g
      PS samples was inversely proportional to the precursor molecular weight of PSLi.
      Direct reactions of PSLi, polybutadienyllithium and n-butyllithium with pristine
      MWNTs without any functional groups were also performed in the presence and in
      the absence of tetrahydrofuran in benzene. The grafting reactions of living
      macroanions either with MWNTs-COCl or with pristine MWNTs indicated a partial
      grafting of polymer on the carbon nanotubes in benzene at room temperature.

PMID- 17450927
TI  - A comparative study on SWCNT and DWCNT field-effect transistors.
AB  - Field-effect transistors have been fabricated using single-walled carbon
      nanotubes (SWCNTs) and double-walled carbon nanotubes (DWCNTs), and their
      electrical transport properties have been studied comparatively. While a
      semiconducting SWCNT exhibits better field-effect characteristics than a DWCNT
      counterpart, the DWCNT shows more complicated response to external gate
      modulation. Depending on the nature of the two shells of a DWCNT, i.e., whether
      the shell is semiconducting (S) or metallic (M), a DWCNT device can be described
      as either S-S, or S-M, or M-S, or M-M. It was found that the S-S and M-M or M-S
      devices show similar field-effect characteristics to those found in SWCNT
      devices. But for S-M DWCNT devices, distinct field-effect characteristic was
      found and attributed to the combined effects of intershell interactions and
      screening by free carriers of the inner metallic shell. The S-M DWCNT devices
      thus provide a perfect system for studying the important intershell interaction,
      and information on the effect of this interaction on the electrical properties of
      a multi-walled carbon nanotube can be obtained by a comparative study of S-M
      DWCNT and S-SWCNT devices.

PMID- 17450928
TI  - Multicomponent and multidimensional carbon nanotube micropatterns by dry contact
      transfer.
AB  - One of the critical aspects of nanotechnology is to assemble different nanoscale
      components into a single system. In such a multicomponent system, the overall
      functionality depends strongly on the precise location and structural
      characteristics of each of the constituent components. In this context, we have
      prepared multicomponent micropatterns of silica particles interposed within the
      discrete areas of aligned multiwall carbon nanotubes. The patterns were
      fabricated by dry contact transferring aligned carbon nanotubes onto a tape pre
      patterned with a thin layer of gold structure, followed by region-specific
      adsorption of thiol-modified silica particles onto the gold surface from
      solution. The dry contact transfer technique has further enabled us to develop
      micropatterns of aligned single-wall carbon nanotubes with interdispersed non
      aligned multiwall carbon nanotubes and microsized carbon fibers sheathed with
      micropatterned aligned carbon nanotubes.

PMID- 17450929
TI  - Anisotropic thermal diffusivity characterization of aligned carbon nanotube
      polymer composites.
AB  - The anisotropic thermal diffusivity of aligned carbon nanotube-polymer composites
      was determined using a photothermoelectric technique. The composites were
      obtained by infiltrating poly-dimethyl siloxane (PDMS) in aligned multiwall CNT
      arrays grown by chemical vapor deposition on silicon substrates. The thermal
      diffusivities are insensitive to temperature in the range of 180 K-300 K. The
      thermal diffusivity values across the alignment direction are approximately 2-4
      times smaller than along the alignment direction and larger than effective media
      theory predictions using reported values for the thermal diffusivity of
      millimeter thick aligned multiwall carbon nanotube arrays. The effective room
      temperature thermal conductivity of the composite along the carbon nanotube
      alignment direction is at least 6X larger than the thermal conductivity of the
      polymer matrix and is in good agreement with the effective media predictions.
      This work indicates that infiltration of long and aligned carbon nanotube arrays
      is currently the most efficient method to obtain high thermal conductivity
      polymer composites.

PMID- 17450930
TI  - Surfactant assisted solid-state synthesis and gas sensor application of a
      SWCNT/SnO2 nanocomposite material.
AB  - Although tin oxide has been the most widely investigated metal oxide material for
      gas detection, it suffers from the large resistance and high operating
      temperature. This could be overcome by hybridization with nanostructured carbon.
      In this work, tin oxide nanoparticles with ultrasmall sizes of 1-3 nm have been
      uniformly coated onto bundles of single-walled carbon nanotubes by a surfactant
      assisted solid state synthesis approach for the first time. Gas sensor properties
      of the as-synthesized nanocomposite material toward NO2 (from 5 to 60 ppm) are
      measured at 150 degrees C. Compared to the pure carbon tubes gas sensors, the
      nanocomposite gas sensor responds to NO2 in low concentrations with good
      linearity, high sensitivity, and fast recovery, while working at a relatively low
      temperature.

PMID- 17450931
TI  - Raman and electrochemical impedance studies of sol-gel titanium oxide and single
      walled carbon nanotubes composite films.
AB  - Titanium oxide grown by a sol-gel route on single-walled carbon nanotubes was
      studied by Raman and Electrochemical Impedance techniques and compared with
      mixtures obtained by mechanical grinding. In spite of the superior dispersion of
      single-walled carbon nanotubes bundles in sol-gel composites, the lost of the
      small-diameter carbon nanotubes in the oxidizing sol-gel bath was inferred from
      their Raman spectra and the lower capacitive current of the voltammograms in 0.1
      M H2SO4. We proposed proton electrosorption as the main charge storage mechanism
      for sol-gel composites, favoured by the hydroxylation and n-type conductivity of
      the oxide, while electrodes based on mixtures were dominated by double-layer
      charging, developing some pseudocapacitance with potential cycling due to the
      reversible oxidation of carbon nanotubes. Comparsion with TiO2/Carbon Blacks
      composites shows the effective role of single-walled carbon nanotubes as
      templates to control the mesoporous nature of sol-gel composite electrodes.

PMID- 17450932
TI  - Morphology and N2 permeability of multi-wall carbon nanotube--Teflon membranes.
AB  - We prepared buckypapers with surface densities in the 1.13-5.66 mg x cm(-2) range
      by filtering multi-wall carbon nanotube (MWCNT) suspensions in acetyl-acetone
      (acac) and dimethylformamide (DMF) through 0.45 microm nylon filters. Filtration
      curves were evaluated using the Carman equation. The average resistance of the
      filter itself was found to be Rm = 3.79 x 10(10) m(-1) for acac and 8.49 x 10(10)
      m(-1) for DMF The specific resistance a of the filter cakes decreased with
      increasing film surface density from 16.1 x 10(12) m x kg(-1) (for the 1.13 mg x
      cm(-2) film from DMF) to 4.38 x 10(12) m x kg(-1) (for the 5.66 mg x cm(-2) film
      from DMF). The effective diffusivity of N2 at 298 K and a pressure difference of
      10 mbar was also determined for all membranes and found to fall into the 1.14 x
      10(-9)-3.74 x 10(-9) m2 x s(-1) range. Both the porosity and the tortuosity of
      buckypapers increased with their thickness. An approx. 5 microm thick Teflon
      (PTFE) coating was applied to the MWCNT membranes by pulsed laser deposition. The
      gas permeability of the MWCNT-PTFE membranes matches that of the uncoated
      nanotube films. This observation is an agreement with our SEM and AFM data on
      porous coating morphology.

PMID- 17450933
TI  - Preparation of multiwalled carbon nanotubes-platinum-Nafion-glucose oxidase
      nanobiocomposite and its application to glucose biosensor.
AB  - Platinum (Pt) nanoparticles were electrodeposited within multiwalled carbon
      nanotubes-Nafion-glucose oxidase (MWNTs-Nafion-GOx) nanobiocomposite by a
      potentiostatic method. The morphology and nature of the resulting MWNTs-Pt-Nafion
      GOx nanobiocomposite were characterized by field emission scanning electron
      microscopy (FESEM), transmission electron microscopy (TEM), and energy dispersive
      X-ray spectroscopy (EDS). The electrocatalytic properties of the MWNTs-Pt-Nafion
      GOx nanobiocomposite film modified glassy carbon electrode were characterized by
      cyclic voltammetry and amperometry in the presence of hydrogen peroxide. The
      glucose biosensor sensitivity was strongly influenced by the deposits of Pt
      nanoparticles and amount of GOx concentration within the MWNTs-Pt-Nafion-GOx
      nanobiocomposite film. The optimized glucose biosensor displayed a sensitivity of
      640 nA mM(-1), a linear range of up to 4 mM, a detection limit of 4 microM, and a
      response time of less than 4 s at an operating potential of +500 mV versus
      Ag/AgCl (3 M KCl).

PMID- 17450934
TI  - Electrochemical biosensor based on multi-walled carbon nanotubes and Au
      nanoparticles synthesized in chitosan.
AB  - A new biosensor is prepared by cross-linking glucose oxidase (GOD) with
      glutaradehyde at the electrode combining Au nanoparticles (AuNP) with multi
      walled carbon nanotubes (MWCNTs). Au nanoparticles-doped chitosan (CS) solution
      (AuNP-CS) is prepared by treating the CS solution followed by chemical reduction
      of Au (III) with NaBH4. MWCNTs are then dispersed in AuNP-CS solution. TEM, FT
      IR, and UV-Vis show that the AuNP-CS solution is highly dispersed and stable. The
      synergistic effect between AuNP and CNTs of the AuNP-CNTs-CS material has been
      investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy
      (EIS) and amperometric methods. The modified glassy carbon electrode (GCE) allows
      low-potential detection of H2O2 with high sensitivity and fast response time.
      With the immobilization of GOD, a biosensor has been constructed. In phosphate
      buffer solutions (PBS, pH 7.0), nearly free interference determination of glucose
      has been realized at 0.4 V(vs. Ag/AgCl/3.0 M KCI) with a wide linear range from
      2.0 x 10(-5) to 1.5 x 10(-2) M and a fast response time within 5s. The biosensor
      has been used to determine glucose in human serum samples and the results are
      satisfactory.

PMID- 17450935
TI  - Multi-walled carbon nanotube-based glucose/O2 biofuel cell with glucose oxidase
      and laccase as biocatalysts.
AB  - This study describes a multi-walled carbon nanotube-based glucose/O2 biofuel cell
      with glucose oxidase and laccase as the anodic and cathodic biocatalysts,
      respectively. Upon being functionalized with L-a-phosphatidylcholine, one kind of
      lipid, multi-walled carbon nanotubes can serve as a support for glucose oxidase
      to form a three-dimensional, conducting and uniform bioanode that possesses a
      good bioelectrocatalytic activity toward the oxidation of glucose biofuel with
      solution-phased ferrocene monocarboxylic acid as the mediator to shuttle the
      electron transfer between glucose oxidase and multi-walled carbon nanotubes. In a
      similar way, the lipid-functionalized multiwalled carbon nanotubes can also be
      used to support the cathodic biocatalyst, i.e., laccase, and, more remarkably, to
      facilitate the direct electron transfer of laccase. As a result, the prepared
      biocathode is very active toward the reduction of oxygen without using any
      electron-transfer mediators. The biofuel cell has a 0.45 V open circuit potential
      and 34 microA/cm2 short circuit current density in phosphate buffer (pH 6.0)
      separated with Nafion-117 membrane with anodic compartment containing 15 mM
      glucose and 2 mM ferrocene monocarboxylic acid and with cathodic compartment
      being saturated with O2 at room temperature. A maximum power density of 3.2
      microW/cm2 is obtained with ca. 0.2 V potential output.

PMID- 17450937
TI  - Effects of antisense-myc-conjugated single-walled carbon nanotubes on HL-60
      cells.
AB  - Antisense therapy is limited in application in clinical therapy because of two
      existing problems: rapid degradation of antisense nucleic acids and poor
      diffusion across the cell membrane. Here we report the use of single-walled
      carbon nanotubes as delivery system for transporting antisense myc into HL-60
      cells. Antisense-myc-conjugated single-walled carbon nanotubes were synthesized,
      characterized by atomic force microscopy (AFM), fluorescent microscopy, and Raman
      spectroscopy. Incubated with HL-60 cells at 37 degrees C, the single-walled
      carbon nanotubes (SWNTs) inside HL-60 cells were measured quantitatively by HPLC.
      Expression of c-myc gene and protein were analyzed by reverse transcriptase PCR
      and Western blot, respectively. Results showed that as-myc-conjugated SWNTs
      dropped character peaks at quadruple wavenumber (cm(-1)) compared with SWNTs, and
      could enter into HL-60 cells within 15 min after incubation, whose uptake amounts
      by HL-60 cells increased as the incubation time increased. After 48 hours, the
      amount of SWNTs in HL-60 cells began to decrease. Compared with as-myc and SWNTs,
      as-myc-conjuagted SWNTs exhibited the strongest inhibition on the proliferation
      of HL-60 cells, induced cell apoptosis, and down-regulated lowest expression of c
      myc gene and C-MYC protein. The SWNTs can directly deliver as-myc into HL-60
      cells, enhance the inhibition of as-myc on HL-60 cells, and is likely a better
      delivery system for antisense therapy. Antisense modified SWNTs can be used for
      intracellular gene regulation with potential applications in tumor therapy and
      drug delivery.

PMID- 17450936
TI  - Enhanced oxidation of estrone at multi-wall carbon nanotubes film electrode:
      direct evidence for the advantage of carbon nanotubes over other carbonaceous
      materials.
AB  - The electrochemical behaviors of estrone at various carbonaceous nanomaterials
      dihexadecyl hydrogen phosphate (DHP) composite films coated glassy carbon
      electrodes were investigated by cyclic voltammetry (CV), linear sweep voltammetry
      (LSV), chronocoulometry (CC) and electrochemical impedance spectroscopy (EIS).
      Comparing with the composite films of acetylene black (AB) and carbon nanofiber
      (CNF), multi-wall carbon nanotubes (MWCNTs)-DHP film showed the best
      electrochemical performance towards the oxidation of estrone, reflected by the
      significantly enhanced oxidation current in the voltammograms as well as the
      apparently reduced charge transfer resistance in EIS. Studies on the active
      surface area, the surface coverage and EIS suggested that the apparently improved
      electrochemical responses of estrone at MWCNTs should arise from their large
      surface area, good conductivity and the ability to facilitate the charge transfer
      process. The reaction mechanisms of estrone oxidation at the three composite
      films were also discussed, which were expected to follow a process involved the
      total loss of two electrons and two protons.

PMID- 17450938
TI  - Comparisons of adsorbent cost for the removal of zinc (II) from aqueous solution
      by carbon nanotubes and activated carbon.
AB  - The reversibility of Zn2+ sorption onto single-walled carbon nanotubes (SWCNTs),
      multi-walled carbon nanotubes (MWCNTs) and powdered activated carbon (PAC) was
      investigated to evaluate their repeated availability performance in water
      treatment. Under the same conditions, the Zn2+ sorption capacity of SWCNTs and
      MWCNTs was more than that of PAC and could be maintained after several cycles of
      water treatment and regeneration. A statistical analysis on the replacement cost
      of these adsorbents based on the best-fit regression of the measured equilibrium
      capacity of each water treatment cycle was also conducted. The results revealed
      that the SWCNTs and MWCNTs could be reused through a large number of water
      treatment cycles and thus appear cost-effective in spite of their high unit cost
      at the present time.

PMID- 17450939
TI  - An algorithm for constructing various kinds of nanojunctions using zig-zag and
      armchair nanotubes.
AB  - A method for generating various forms of junctions involving armchair and zig-zag
      nanotubes, firstly introduced by Zsoldos et al., is developed to cover all types
      of armchair and zig-zag nanotubes in a systematical way. This method can also be
      used to produce nanogears and toothed canals. The method is explained and
      flowcharts are included to aid in programming into a code.

PMID- 17450940
TI  - Quantum chemical molecular dynamics study of "shrinking" of hot giant fullerenes.
AB  - We present a detailed analysis of size-down trajectories of the "Shrinking Hot
      Giant" road of fullerene formation, revealed before by our quantum chemical
      molecular dynamics simulations. It is found that shrinkage of giant fullerenes
      occurs in two stages, fall-off and pop-out stage, respectively, and that it is an
      irreversible process occurring naturally at high temperatures. The driving force
      behind the energetically unfavorable C2 evaporation is the increase in entropy
      and pi-conjugation stabilization of the increasingly more spherical fullerene
      cages. A comparison of the theoretical results with existing experimental data
      shows the importance of annealing for the synthesis of smaller (C60, C70)
      fullerenes.

PMID- 17450942
TI  - Enhanced stability of enzymes adsorbed onto nanoparticles.
AB  - We have discovered that the highly curved surface of C60 fullerenes enhances
      enzyme stability in strongly denaturing environments to a greater extent than
      flat supports. The half-life of a model enzyme, soybean peroxidase, adsorbed onto
      fullerenes at 95 degrees C was 117 min, ca. 2.5-fold higher than that of the
      enzyme adsorbed onto graphite flakes and ca. 13-fold higher than that of the
      native enzyme. Furthermore, this phenomenon is not unique to fullerenes, but can
      also be extended to other nanoscale supports including silica and gold
      nanoparticles. The enhanced stability was exploited in the preparation of highly
      active and stable polymer-nanocomposite films. The ability to enhance protein
      stability by interfacing them with nanomaterials may impact numerous fields
      ranging from the design of diagnostics, sensors, and nanocomposites to drug
      delivery.

PMID- 17450941
TI  - Molecular dynamics simulation of polyamidoamine dendrimer-fullerene conjugates:
      generations zero through four.
AB  - Previously the synthesis of the polyamidoamine (PAMAM) (G4)-C60 conjugate with a
      molar ratio of 1 : 30 was reported. Because PAMAM G4 has sixty-four primary amine
      groups, it was hypothesized that approximately two surface amine groups react
      with each fullerene molecule to form the conjugates. A computational energy
      minimization study of various G4 PAMAM-fullerene conjugates containing 1
      dendrimer but different amounts of fullerenes shows excellent stability for the 1
      : 30 dendrimer to fullerene product. Attempts to prepare other PAMAM dendrimer
      fullerene (C60) conjugates, using generations G0-G3 of PAMAM and C60 via the same
      procedure in pyridine were not successful, possibly due to solubility
      differences. The same computational techniques used to study the G4 conjugates
      were then used to determine (1) the stability of the G0-G3 conjugates (with a 2 :
      1 primary amine to fullerene ratio), and (2) their solubility in pyridine
      compared to the (G4)-C60 conjugate. The findings allow for a better understanding
      of structure-property relationships of these nano-hybrid materials, through
      investigation of the molecular shape and radius of gyration. The findings
      reported herein may lead to improved syntheses of fullerene-dendrimer conjugates
      of various sizes and a better understanding of their nanoscopic structures and
      topographical influences.

PMID- 17450943
TI  - Vertically aligned carbon nanotubes as cytocompatible material for enhanced
      adhesion and proliferation of osteoblast-like cells.
AB  - In this study, we describe the spatial organization of CAL-72 osteoblast-like
      cells on arrays of vertically aligned multi-walled carbon nanotubes (VACNTs). It
      was observed that, unlike cell growth on non-patterned surfaces, the cell
      attachment and spreading process on VACNTs was significantly enhanced.
      Additionally, since carbon nanotubes are known to possess resilient mechanical
      properties and are chemically stable, the effect of periodic arrays of VACNTs on
      CAL-72 osteoblast-like cells was also studied. The periodicity and alignment of
      VACNTs considerably influenced growth, shape and orientation of the cells by
      steering toward the nanopattern. This situation is of great interest for the
      potential application of VACNTs in bone bioenginnering. This data provides
      evidence that CAL-72 osteoblast-like cells can sense physical features at the
      nanoscale. These results give a fascinating insight into the ways in which cell
      growth can be influenced by man-made nanostructures and could provide a framework
      for achieving controlled cell guidance with controlled organization and special
      physical properties.

PMID- 17450944
TI  - Effect of filler geometry on interfacial friction damping in polymer
      nanocomposites.
AB  - Single-walled carbon nanotube polycarbonate and C60 polycarbonate nanocomposites
      were fabricated using a solution mixing method. The composite loss modulus was
      characterized by application of dynamic (sinusoidal) load to the nanocomposite
      and the pure polymer samples. For a loading of 1 weight %, the single-walled
      nanotube fillers generated more than a 250% increase in loss modulus compared to
      the baseline (pure) polycarbonate. Even though the surface area to volume ratio
      and surface chemistry of C60 is similar to that for nanotubes, we report no
      significant increase in the energy dissipation for the 1% weight C60 nanoparticle
      composite compared to the pure polymer. We explain these observations by
      comparing qualitatively, the active sliding area (considering both normal and
      shear stresses) for a representative volume element of the nanotube and the
      nanoparticle composites. These results highlight the important role played by the
      filler geometry in controlling energy dissipation in nanocomposite materials.

PMID- 17450945
TI  - [Estimation of the asymptomatic latent period of alveolar hydatidosis in patients
      infected in foreign endemic areas].
AB  - Alveolar hydatidosis (AH) is a parasitic disease with an extremely long latent
      period which has an important role in the endemic of human AH. The individual and
      average latent periods of human AH were estimated from the case histories of 19
      male patients who were infected in foreign endemic areas and diagnosed surgically
      and pathologically as having AH after returning to Honshu, mainland of Japan. The
      beginning (A) and the end (C) of stay in foreign endemic areas of AH, and the
      midpoint (B) between (A) and (C), the time of onset of symptoms (D) and death (E)
      of AH were determined in the case reports. The period (D-B) from the midpoint (B)
      to the onset of symptoms (D) was considered as an individual latent period of AH,
      and the average latent period was estimated from D-B periods. The individual
      latent periods ranged from 3 to 44 years, and the average was 20 +/- 10 (mean +/-
      SD) years in the 19 cases. The average latent period was longer in 7 surviving
      cases (26 +/- 12) than in 12 fatal cases (16 +/- 7) at the publication of the
      case reports, but there was no statistically significant difference between them.
      The estimated latent period in this report was very close to that by Doi et al.
      (2000), and the traditional 5-15 years should be changed to 7-35 years.

PMID- 17450946
TI  - Age estimation from quantitative evaluation of atherosclerosis of abdominal aorta
      in Japanese.
AB  - To assess validity of age estimation from the degree of atherosclerosis of
      abdominal aorta, we quantitatively evaluated the atherosclerotic parameters
      (surface involvement of atherosclerotic lesions, atherosclerotic index, and
      aortic width at renal arteries and common iliac bifurcation, which was measured
      by using digital photographs at autopsy), and collected individual factors (age,
      sex, body height, body weight and heart weight, and body surface, body mass index
      and cardiomegaly index) in autopsied 103 bodies (62 males, 41 females) during 2
      years. We statistically examined their data by multiple regression analysis to
      determine the effects of the individual factors on the proceeding parameters of
      atherosclerosis, and obtained correlation coefficient, regression equation, and
      standard error of estimate between the atherosclerotic parameters and age. Among
      the factors, only age was influential on all the atherosclerotic parameters, of
      which the surface involvement (SI%) and the aortic width at common iliac
      bifurcation (Wb cm) were acceptable as the parameters for age estimation, and
      useful in a wide age range, according to the results of the standard errors of
      estimate. We also recognized predicting formulae for age (Y) by multiple
      regression analysis; Y = 0.52SI + 9.53Wb - 4.41 in males and Y = 0.34SI + 18.47Wb
      - 23.32 in females.

PMID- 17450948
TI  - Kentucky health system starts online consumer portal program. Web site
      development aims to drive consumerism and market service lines.
AB  - Saint Joseph HealthCare in Lexington, KY, is a three-hospital health system
      comprised of more than 650 beds serving the state's central and eastern regions.
      As a leading provider in cardiology, orthopedics, and stroke, it was recognized
      in 2006 as a top hospital in the nation by U.S. News and World Report.

PMID- 17450947
TI  - Online promotion a must for hospital marketing professionals. Employ tactics to
      ensure your Web site is working to build your brand.
AB  - Maintaining an online presence and more effectively executing Web-based marketing
      strategies can help you better target consumers and increase brand recognition,
      says Eric Anderson, director of agency services at interactive marketing agency
      White Horse in Portland, OR. With consumers heading to the Internet for health
      information now more than ever, it's in your best interest to not only have a
      well-designed, user-friendly Web site, but also to take advantage of the
      Internet's capabilities with blogs and microsites.

PMID- 17450949
TI  - Hospital CEO raises awareness through blog.
AB  - Four years ago, Nick Jacobs didn't know what the term "blogging" meant. As the
      president and CEO of the Windber (PA) Research Institute and the Windber Medical
      Center, that's not surprising. But this not-so-typical hospital president changed
      all that by launching his own blog three years ago and putting his small, 82-bed
      facility on the map.

PMID- 17450950
TI  - Merger campaign.
AB  - Through using the Web, TV, radio, and print advertisements, The Hospital of
      Central Connecticut announced in October 2006 its new name and the merger of two
      hospitals: New Britain General Hospital and Bradley Memorial Hospital. A campaign
      consisting of TV and radio ads was created to promote the merger. The ads are
      also featured on the hospital's Web site.

PMID- 17450951
TI  - TV on the Web.
AB  - Children's Hospital & Research Center of Oakland, CA, launched a TV campaign
      focusing on athletic children to promote its excellent pediatric care. The TV
      campaign is also featured on the hospital's Web site. There are also five 15
      second spots that offer parents handy tips on how to deal with injuries faced by
      an athletic child.

PMID- 17450952
TI  - Awareness campaign.
AB  - LifeBridge Health developed and implemented an awareness campaign to generate
      buzz about the breast cancer services at the Alvin & Lois Lapidus Cancer
      Institute of LifeBridge Health and the Herman & Walter Samuelson Breast Cancer
      Care Center at Northwest Hospital Center. With the help of talented local breast
      cancer survivors, celebrities, fashion designers, and artists, LifeBridge Health
      created a campaign, including an interactive Web site, public relations outreach,
      and a unique event in October 2006 that featured a collection of hand-made
      decorated bras.

PMID- 17450953
TI  - Comparisons of mosquito populations before and after construction of a wetland
      for water quality improvement in Pitt County, North Carolina, and data-reliant
      vectorborne disease management.
AB  - Wetlands serve an important purpose in flood control and water quality, but
      constructed-wetland sites also provide habitats for mosquito breeding.
      Communities near constructed-wetland sites often raise a "mosquito" objection
      when constructed wetlands are proposed. Wildlife and wetland advocates can
      confuse the public by making unsubstantiated claims about natural predators
      eliminating or controlling mosquito problems in a constructed wetland. Management
      of constructed-wetland mosquito habitat, with adequate mosquito surveillance and
      data analysis, can help lead to a successful project and satisfied citizens. The
      cooperative project described in this paper, was conducted in the town of
      Simpson, North Carolina, and was designed to determine the mosquito population
      impact of wetland construction at Mill Branch Stream, a small tributary of the
      Tar River in Eastern North Carolina. In the authors' analysis of three years of
      mosquito surveillance data, month (time of year standing in for temperature and
      day length) was a significant factor in regression analysis for mosquito numbers,
      but rainfall was not. Numbers of mosquitoes were not found to be significantly
      higher after construction than before construction.

PMID- 17450954
TI  - California's county and city environmental health services delivery system.
AB  - The purpose of the authors' research was to assess the current status of county
      and city environmental health service delivery in California with the aim of
      providing a foundation for informed decision making about environmental health
      service delivery. Standardized interviews were conducted from March 2005 to May
      2005 with 55 (88 percent) of the 62 county and city directors of environmental
      health; their jurisdictions represented 90 percent of the state's population and
      94 percent of the landmass. Relevant databases and other publicly available
      information germane to project goals were also evaluated. The directors who were
      interviewed reported a total of 2,477 professional environmental health staff
      employed in county and city agencies, complemented by 520 support personnel.
      Percentages of respondents reporting technical-training needs were greatest for
      Certified Unified Program Agency (CUPA) activities (60 percent), dairy programs
      (57 percent), and septic-system programs (55 percent), while nontechnical
      training was desired in conflict resolution (55 percent), written/oral
      communication (49 percent), and problem solving (49 percent). Sixty-seven percent
      (67 percent) of directors reported difficulty in recruiting qualified applicants.
      Fifty-six percent (56 percent) were familiar with the 10 essential services of
      environmental health, while only 11 percent collected and reported health outcome
      measures to demonstrate agency effectiveness. The study team concluded that at
      the local level, environmental health services are largely provided as a
      reflection of local need; however, this tendency toward customization leads to
      stakeholder confusion about the purpose and value of environmental health
      services. The authors offer seven recommendations for improving environmental
      health services in California. Many of these recommendations can be generalized
      to the nation at large.

PMID- 17450955
TI  - Eco-friendly control of mosquito larvae by Brachytron pratense nymph.
AB  - The study reported here revealed the biocontrol efficacy of aquatic nymphs of the
      dragonfly Brachytron pratense against larvae of the mosquito Anopheles subpictus.
      It was found that during a 24-hour study period, a nymph of B. pratense would
      consume (mean value of three observations) 66 fourth-instar An. subpictus larvae
      released in a water bowl containing 3 liters of pond water. The consumption rate
      was significantly higher (p < .05) during the lights-on phase of the experiment
      than during the lights-off phase (t = 2.15). Under field conditions, a
      significant decrease (p < .05) in larval density in dipper samples was observed
      15 days after the introduction of dragonfly nymphs (10 individuals) in concrete
      tanks. The biocontrol potential of the nymphs under field conditions was also
      indicated by a significant increase (p < .05) in the density of mosquito larvae
      15 days after the removal of nymphs. In the control tanks (where no nymphs were
      introduced), mean larval-mosquito density did not differ significantly throughout
      the study period (p > .05).

PMID- 17450956
TI  - Veterinarians and environmental health practitioners: partners in prevention.

PMID- 17450957
TI  - A legal history of raw milk in the United States.

PMID- 17450958
TI  - My generation! (and its legacy).

PMID- 17450959
TI  - Can "hospital food" be synonymous with nutrition and quality?

PMID- 17450960
TI  - Psychometrics and psychometricians in the 20th and 21st centuries: how it was in
      the 20th century and how it is now.
AB  - This article is based largely upon the author's invited address at the 113th
      annual convention of the American Psychological Convention, Washington, DC, as
      the 2005 recipient of the Samuel J. Messick Award bestowed by APA Division 5 and
      the Educational Testing Service. The author summarizes the growth of graduate
      training in psychometrics and quantitative psychology, in the years prior to and
      following the end of WWII. He then opines the steady decline in the training of
      psychometricians and quantitative psychologists beginning in the 1970s and
      continuing into the 20th century. Likely causes of the decline are inferred and
      prospects for strengthening the quantitative skills of doctorates are discussed,
      including recommendations for reversing the downward trend.

PMID- 17450961
TI  - Height of chair seat and movement characteristics in sit-to-stand by young and
      elderly adults.
AB  - The height of a chair seat affects the burden on the lower limbs during the sit
      to-stand (STS). To develop an objective test to evaluate muscle function of the
      lower limbs using floor reaction force during a STS, the relationship between
      chair-seat height and the burden on the lower legs must be assessed. To examine
      the influence of the chair-seat height, floor reaction forces during a STS
      performed with 5 chair heights adjusted to each subject's lower leg length were
      compared. The force production and quickness of movement tended to decrease in
      the phases of trunk flexion and knee and hip joint extension when performing a
      STS from a lower chair, when the chair height differed by 20% (6.2 cm) from the
      lower leg length, and was marked when the difference between chair height and
      lower leg length became larger. In 52 elderly and 50 young adults, floor reaction
      forces during a STS performed from a chair of the same height as subjects' lower
      leg lengths were compared. Elderly persons were inferior in force production
      (strength) and quickness of movement, which decreased as elderly stood up from a
      chair of a lower height.

PMID- 17450962
TI  - Effect of simultaneous model observation and self-modeling of volleyball skill
      acquisition.
AB  - This study examined the effect of feedback with simultaneous skilled model
      observation and self-modeling on volleyball skill acquisition. 53 pupils 12 to 15
      years old formed two experimental groups and one control group who followed an
      intervention program with 12 practice sessions for acquisition and retention of
      how to receive a ball. Groups received different types of feedback before and in
      the middle of each practice session. Reception performance outcome (score) and
      technique in every group were assessed before and at the end of the intervention
      program and during the retention phase. A 3 (Group) x 3 (Measurement Period)
      multivariate analysis of variance with repeated measures was applied to
      investigate differences. Results showed equivalent improvement in all three
      groups at the end of the intervention program. In conclusion, types of augmented
      feedback from the physical education teacher are effective in acquisition and
      retention of the skill for reception in volleyball.

PMID- 17450963
TI  - Memory performance in abstinent 3,4-methylenedioxymethamphetamine (MDMA,
      "ecstasy") users.
AB  - Research with animals and humans has suggested that acute and subacute use of 3,4
      methylenedioxymethamphetamine (MDMA "ecstasy") may lead to memory impairment.
      However, research is limited by (1) low power due to small sample sizes, (2) the
      possible confound of polydrug use, and (3) the failure to consider intelligence
      as a covariate. The present study compared the memory performance on the Wechsler
      Memory Scale-III of 26 abstinent (2-wk. minimum) recreational MDMA users with 26
      abstinent (2-wk. minimum) recreational polydrug users. Despite significantly
      greater polydrug use amongst these MDMA users, no significant group differences
      in memory were observed. Regression of total lifetime amount of MDMA use also did
      not predict memory performance after accounting for intelligence. In addition,
      the length of time since abstinence (at least 2 wk.) was not associated with an
      increase in memory performance. Greater total lifetime cocaine use, rather than
      total lifetime MDMA use, was significantly associated with greater decrements in
      General Memory and Delayed Verbal Memory performance.

PMID- 17450964
TI  - Diminished plantar cutaneous sensation and postural control.
AB  - The purpose of this study was to assess the effect of diminished plantar
      cutaneous sensation induced by cooling on postural control during double- and
      single-limb quiet standing. 32 healthy adults were tested on an intervention day
      and control day. The intervention consisted of 10 min. of ice immersion of the
      plantar aspect of the feet prior to balance testing. Dependent variables were
      center of pressure velocity and area during double- and single-limb stance with
      eyes open and closed. Significant interactions were found between sensation and
      vision for double-limb center of pressure area, with a significant reduction in
      area of center of pressure excursions after reducing sensation with eyes closed
      but not with eyes open. The area of center of pressure excursions may have been
      reduced in an effort to curtail exploratory postural behavior given the altered
      afferent input from plantar receptors. There were no significant differences for
      plantar hypoesthesia in single-limb stance.

PMID- 17450965
TI  - Does stimulant medication decrease the lower extremity response times of children
      with and without attention-deficit/hyperactivity disorder?
AB  - In 2005 Pedersen and Surburg reported that stimulant medications reduced the
      lower extremity response times of 16 boys with Attention-Deficit/Hyperactivity
      Disorder. However, as boys without ADHD and girls with and without ADHD were not
      studied, one cannot conclude that reported effects represent a medication effect
      unique to children with ADHD. An alternative hypothesis is presented: that
      stimulant medications produce an excitatory effect in the central nervous system
      by increased occupancy of postsynaptic dopamine receptors to reduce the lower
      extremity response times of children in general. Well-designed controlled
      clinical trials are needed to evaluate this hypothesis.

PMID- 17450966
TI  - Relations of attachment styles and group cohesion in premier league female
      volleyball players.
AB  - The relations of attachment styles with group cohesion were monitored for premier
      league female volleyball teams. 74 volleyball players from 8 teams responded to
      the Relationship Scales Questionnaire and Group Environment Questionnaire.
      Pearson correlations indicated significant association of attachment styles with
      group cohesion. Specifically, a significant negative correlation was found
      between female volleyball players' individual attraction to the group-social
      subscale and fearful attachment style. In addition, there was a significant
      positive correlation for scores on the group integration-social and secure and
      preoccupied attachment subscales and a significant negative correlation for
      scores on the group integration-task subscale and preoccupied attachment style.
      In conclusion, attachment styles might be considered important in predicting
      group cohesion

PMID- 17450967
TI  - Self-reported versus measured weight and height by adolescent girls: a Croatian
      sample.
AB  - Self-reported and measured weight and height of 234 Croatian girls in Grades 5,
      8, and 11 were used to explore the validity of these measures for calculating
      Body Mass Index. For both weight and height, the correlations between self
      reported and measured values were over .93. Overweight girls underreported their
      weight and overreported their height.

PMID- 17450968
TI  - Spectators' identification with French sports teams: a French adaptation of the
      sport spectator identification scale.
AB  - Due to the works of Wann and colleagues, spectators' identification with teams
      has taken on a central role in the study of sports spectators' thought and
      behavior. However, no research in this area has measured identification with
      sports teams in the French context. Two studies attempted to develop a valid and
      reliable French version of the Sport Spectator Identification Scale (SSIS)
      developed by Wann and Branscombe in 1993 to measure team identification. In Study
      1, 200 physical education students completed a French translation of the SSIS and
      several questions concerning their involvement, investment, and evaluation of the
      team's future performance. Results showed that the French translation of the SSIS
      is a reliable and one-dimensional instrument: strong relationships were found
      between identification with professional French teams and these variables. In
      Study 2, 143 physical education students completed the SSIS with a National sport
      team as the target team. Results confirmed the psychometric properties of the
      scale and indicated that persons who strongly identify with the National soccer
      team reported more involvement with the team and were more optimistic about
      future performances than persons low in identification.

PMID- 17450969
TI  - Role of age in relation between two kinds of abilities and performance in
      acquisition of new motor skill.
AB  - Better understanding of age-related differences in skilled performance was the
      focus of analyses of cognitive-performance scores-relationships in acquisition of
      a new motor skill. 31 younger adults and 33 older adults were tested on both a
      cognitive and a psychomotor test. Then, they were asked to learn a juggling task
      over 12 sessions of 20 min. Analysis indicated age-related differences in the
      rate of learning. Acquisition by the younger adult group was significantly faster
      than that by the older adult group. This difference was also reflected in the
      relationship of cognition and performance for the two age groups. Motor execution
      for the older adults seemed to require more psychomotor ability, especially at
      the end of the learning sessions, and was dependent on cognitive control. This
      trend is consistent with the perspective that cognitive predictors of performance
      are related to age.

PMID- 17450970
TI  - Source confusion as an explanation of cultivation: a test of the mechanisms
      underlying confusion of fiction with reality on television.
AB  - Cultivation studies have found evidence that heavy television viewers adopt a
      world view congruent with how the world is portrayed in fictional television
      programs. An explanation is that viewers may remember fictional TV stories as
      realistic stories or news (fiction-to-news confusion). Until now, fiction-to-news
      confusion was found only if at least a week evolved between watching TV and
      asking viewers what was remembered. The present study conducted with a purposive
      sample of students and employees of a college in The Netherlands (N=96; M age =
      28.6 yr., SD = 10.9) indicates that fiction-to-news confusions can also occur
      almost immediately after watching. In addition, whereas earlier research suggests
      that fiction-to-news confusions are associated with heavy viewing, i.e., more
      confusion when more hours per day are spent on TV viewing in leisure time, and
      faulty memory, the present study more specifically suggests that participants
      make many fiction-to-news confusions when they are exposed to relatively many
      fictional TV fragments that contain threatening, violent events.

PMID- 17450971
TI  - Projective drawings for assessing stress among subjects with medical symptoms
      compatible with sick building syndrome, and validation of a modified version of
      the Stress Load Index from the Drawing Personality Profile: a pilot study.
AB  - It was hypothesized that subjects with medical symptoms would show more signs of
      stress in projective drawings. A Stress Load Index, including five signs of
      stress in drawings, was evaluated. A questionnaire with an instruction to draw "a
      person in the rain" was sent to a cohort of 195 subjects, and the drawings were
      analysed blindly for eight stress items. Men had a higher index than women (p <
      .05) and drew clouds more often (p < .05). Drawing of clouds was associated with
      headache (adjOR = 4.28; 95% CI 1.75; 11.68). Drawing of puddles was associated
      with ocular symptoms (adjOR = 3.22; 95% CI 1.38, 7.50), facial dermal symptoms
      (adjOR= 2.94; 95% CI 1.28, 6.81), and tiredness (adjOR = 2.44; 95% CI 1.05,
      5.67). Drawing of long rain strokes was associated with nasal symptoms (adjOR =
      2.28; 95% CI 1.05, 2.06) and headache (adjOR = 3.20; 95% CI 1.28, 8.05). Age and
      stress load were predictors of sick building syndrome symptoms (p < .05). In
      conclusion, a nonverbal projective drawing test detected sex differences which
      represent directions opposite to those with verbal methods. These need empirical
      assessment.

PMID- 17450972
TI  - Warning: subtle aspects of strategy assessment may affect correlations among
      spatial tests.
AB  - In this study, preliminary to a larger experiment, 42 participants completed four
      different spatial tests and, after each test, a strategy questionnaire. For half
      of the participants, visualizational strategies were presented first in this
      questionnaire, and for the other half, analytical strategies. The order of
      strategy descriptions had effects on the strategies reported and on the
      intercorrelations among the spatial tests and between the spatial tests and an
      inductive-reasoning test. In the group first presented with visualizational
      strategies, intercorrelations among the spatial tests were higher and
      correlations with the reasoning test were lower than in the group first presented
      with analytical strategies. Bootstrap analyses with 100 random splits of the
      sample confirmed this result. The findings are interpreted as indications of a
      priming effect by the strategy descriptions which affected the way participants
      dealt with subsequent tests. Implications for strategy assessment are discussed.

PMID- 17450973
TI  - California Critical Thinking Disposition Inventory: further factor analytic
      examination.
AB  - The stability of the factor structure of the California Critical Thinking
      Disposition Inventory was re-examined using a convenience sample of 800
      undergraduate students from nursing (n=520 first bachelors' and n=185 second
      bachelors' students) and biology (n=95) enrolled in introductory courses in their
      majors at a 4-yr. mid-Atlantic public university. Ages ranged from 17 to 54 years
      (M = 23.0, SD = 5.9), with 92 men and 707 women (1 missing). 685 participants
      identified themselves as Euro-American, 65 as African American, 9 as Hispanic, 26
      as Asian, and 11 as "Other" (4 missing). The inventory developed by Facione in
      1994 is a 75-item, forced-choice, adjective checklist, yielding seven subscores
      and a total score assessing testees' disposition toward critical thinking. A
      principal components factor analysis did not replicate the original factor
      structure of seven factors but supported the stability of a four-factor structure
      which had emerged in previous work by Walsh and Hardy and by Kakai. When the 75
      original items were reduced to 25, the explained variance for the inventory
      improved from 27% to 44.95%. Thus, further investigation and continued refinement
      is warranted.

PMID- 17450975
TI  - Demand characteristics of music affect performance on the Wonderlic Personnel
      Test Of Intelligence.
AB  - This study examined whether demand characteristics concerning music can change
      subjects' performance on the Wonderlic Personnel Test of intelligence.
      Participants (N= 60) were randomly assigned and informed either that Mozart's
      music typically enhances cognitive performance or diminishes it. They then
      completed the Wonderlic Personnel Test while listening to a Mozart piano sonata.
      The subjects with a positive set answered significantly more items correctly on
      the test (14%) than those with a negative set (p = .03). This result may hold
      implications for the study of the 'Mozart effect'.

PMID- 17450974
TI  - Construct validity of the helplessness/hopelessness/haplessness scale:
      correlations with perfectionism and depression.
AB  - In a sample of 117 undergraduates, helplessness scores and the discrepancy scores
      on a measure of perfectionism predicted depression scores, providing evidence for
      construct validity for the hopelessness, helplessness, and haplessness scales.

PMID- 17450976
TI  - Facial expressions are more easily produced on the upper-lower compared to the
      right-left hemiface.
AB  - Clinical research has concentrated on differences in intensity of expression
      between the right and left hemiface as a means to assess hemispheric differences
      in motor control. However, observations by social psychologists suggest that
      control of facial expression may be organized predominantly across the upper
      lower hemiface because during social interactions individuals may produce brief
      facial blends of emotions, in which the upper and lower face display a different
      emotion. Full facial versus upper/lower and right/left facial blends of emotion
      were posed by 20 subjects, 10 men and 10 women ranging in age from 20 to 37
      years. The subjects rated the difficulty of each pose on a 5-point Likert scale.
      Digital photographs of the poses were taken and the full and half-facial poses
      were shown in random order to four judges who indicated what pose was being
      performed. The results were very robust and confirmed that facial blends of
      emotion are more easily and accurately posed on the upper-lower than on the right
      left hemiface. Our results are consistent with recent anatomical studies showing
      separate cortical areas for motor control of the upper versus lower face in
      primates. Based on recent research exploring hemispheric differences in
      perceiving facial blends of emotion, the left hemisphere may be more involved
      with modulating lower facial expressions and the right hemisphere more involved
      with modulating upper facial expressions.

PMID- 17450977
TI  - Attitudes of physical education majors in Turkey towards disability are changed
      by adaptive physical education training.
AB  - This study was designed to investigate the attitudes of university students who
      are prospective physical education teachers toward individuals with physical
      disabilities. 47 college students majoring in physical education (Study group)
      and 34 students from other sports-related departments, i.e., sports management
      and training (Control group), participated in the study. The study group took a
      14-week course on Adapted Physical Education (APE), whereas the control group did
      not. The Attitude Toward Disabled Persons scale, Form O was used to compare the
      attitudes of the groups. Analyses showed no significant difference between the
      groups in terms of attitude towards individuals with physical disabilities at the
      beginning of the semester but a significant difference at semester end. Results
      indicated that the APE course positively influenced attitude of the prospective
      physical education teachers towards individuals with physical disabilities.

PMID- 17450978
TI  - A field experiment comparing different workgroup interactive techniques.
AB  - Participants (N=149) belonging to real life workgroups from different work
      organisations took part in a project with the aim of improving organisational
      culture. Two techniques for enhancing effectiveness were used in the study, the
      individual-group-individual technique and the nominal group technique. In a
      control group were participants in nonstructured interactive groups. Thus, the
      workgroups were randomised into these 3 conditions. Analysis indicated that both
      techniques affect idea generation but not generation of goals.

PMID- 17450979
TI  - Symbolic significance of initials on longevity.
AB  - The longevities of deceased major league baseball players who died prior to 1950
      (N=3835) and whose initials formed acronyms, words, or names with "positive" or
      "negative" affect, as rated a priori by two judges, were compared with those for
      a group of neutral controls matched for birth year and career length, using the
      Berkeley standardized mortality tables. Players (n=11) with positive initials,
      e.g., A.C.E., lived a mean of 13 years longer than players (n=30) with negative
      initials, e.g., D.E.D., or players with neutral initials (n=864). These results
      corroborated a previous study and suggest positive name symbols are associated
      with increased longevity in this sample.

PMID- 17450980
TI  - Relations of physical self-concept and muscular strength with resistance Exercise
      induced Feeling State scores in older women.
AB  - Formerly sedentary older women (M age = 62 yr.) were recruited for either a wait
      list control group (n=40) or a 10-.wk., 3 days/wk. weight-training treatment
      group (n=48). Only the treatment group demonstrated significant before- to after
      exercise improvements on the Exercise-induced Feeling Inventory scales of
      Positive Engagement, Revitalization, Tranquility, and Physical Exhaustion (ds =
      /.43/ to /.96/). For the treatment group, scores on Physical Self-concept of the
      Tennessee Self-concept Scale: 2 were significantly correlated (r = -.28) with
      after-exercise changes in Physical Exhaustion. Muscular strength was
      significantly correlated with after-exercise changes in scores on three Exercise
      induced Feeling Inventory scales (rs= /.28/ to /.31/). Simultaneous entry of
      Physical Self-concept scores and muscular strength into multiple regression
      equations increased the explained variance in Exercise-induced Feeling Inventory
      score changes for each of its four scales. Statistical significance was only
      reached, however, on changes in the Physical Exhaustion scale (R2 = .16, p =
      .02). Limitations and implications for theoretical development and applied use
      were discussed.

PMID- 17450981
TI  - Legibility of small icons with color combinations in small displays.
AB  - The present study explored the effects of figure/ground color combinations on
      legibility of small icons. This experiment used a 2 (icon size) x 3 (icon hue) x
      3 (icon saturation) x 3 (background hue) x 3 (background saturation) x2
      (luminance contrast) factorial design. Legibility was investigated by response
      time of subicons with different factors t hat affect discrimination. 11
      undergraduate students from the National Formosa University in Taiwan were
      recruited to participate in the experiment. Their mean age was 21.8 yr. (SD=3.3).
      Analysis also showed that Icon Size x Luminance Contrast, Background Hue x
      Luminance Contrast, and Background Saturation x Luminance Contrast significantly
      affected response time. The results suggested that the higher Luminance Contrast
      could promote icon legibility but not the icon chromaticity or background
      chromaticity.

PMID- 17450982
TI  - Perceived aggression in sports and its relation to willingness to participate and
      perceived risk of injury.
AB  - The purpose of this study was three-fold: assess relationships among perceived
      hostile aggression, instrumental aggression, and assertion for a set of
      collegiate sports, categorize the sports by rated aggression, and present
      relationships of aggression with ratings of likelihood of career-ending injuries,
      personal willingness to participate, and the perceived desirability of
      participation in the sports by others. The sports were rated on the variables by
      285 undergraduates enrolled in psychology courses in a large private university
      in the western USA. Mean age for men was 23.7 yr. (SD = 2.3) and for women 21.3
      yr. (SD = 2.7). A 4 (rating category) x 16 (sport) repeated-measures analysis of
      variance showed significant main and interaction effects. The sports were
      classified according to level of aggression in post hoc analysis. Perceived risk
      of a career-ending injury was linearly related to aggregate aggression, whereas
      willingness to participate and desirability of the sport for others had quadratic
      relationships to both aggregate aggression and risk of career-ending injury.

PMID- 17450983
TI  - Effects of a 12-month pedometer walking program on gait, body mass index, and
      lower extremity function in obese women.
AB  - This study evaluated the effects of a self-reported pedometer-walking program on
      gait, lower extremity function, and Body Mass Index for 33 obese women, ages 31
      65 years (M = 48.0, SD = 8.0) and whose initial average Body Mass Index was 40.30
      +/- 9.60 kg/m2. During the 12-mo. intervention participants wore pedometers and
      reported the number of daily steps walked. Body Mass Index, three gait
      parameters, steps/day, and lower extremity function were taken over 3-mo.
      intervals. All participants increased in gait velocity, % single-leg support, and
      lower extremity function, and decreased in Body Mass Index over time. Those whose
      steps/day increased by 2000 over 6 mo. had significantly faster velocities and
      longer step lengths than those whose steps/day did not increase. The 1-yr.
      walking program stimulated changes in gait, Body Mass Index, and lower extremity
      function for these obese women. Ultimately, these changes may reduce the risk of
      falls for this group of women.

PMID- 17450984
TI  - Early attention processes and anxiety in children.
AB  - It has been hypothesized that anxiety in children is associated with attentional
      bias in the early stages of information processing. Bias towards threat indicates
      the tendency of an individual to direct attention towards threatening
      information. The aim of the present study was to investigate whether high test
      anxiety in a sample of nonreferred children is associated with attentional bias
      towards threat pictures, and if low test-anxiety is associated with attentional
      bias away from threat pictures. A probe-detection task was used with 44 10- to 13
      yr.-old children. The overall analyses indicated the presence of an attentional
      bias away from threatening pictures in these nonreferred children. However, in
      relation to anxiety, the study did not confirm that high anxious children show an
      attentional bias towards threatening pictures or that low anxious children show
      an attentional bias away from threatening pictures. Yet, higher anxiety did seem
      to be associated with longer mean response times. These longer response times
      might originate from the interpretation of the nature of a stimulus as too
      threatening, compared to the actual threatening content, in the first stage of
      information processing. This finding could be useful to improve treatment methods
      aimed at anxiety symptoms during childhood.

PMID- 17450985
TI  - Perceived effort step-up procedure for self-regulating stationary cycle exercise
      intensity by patients with cardiovascular disease.
AB  - This study examined the strategy utilized by patients with cardiovascular disease
      to regulate exercise intensity using the Rating of Perceived Exertion (RPE) and
      tested if a step-up procedure would reduce overshoot of target heart rate (HR).
      Also the study investigated if Prescription Congruence and Intensity
      Discrimination, components of the Intensity Self-regulation Model, could be
      validated for these patients. An estimation and production paradigm was used. HR
      was measured at 2-min. intervals during 6-min. stationary cycle ergometer
      exercise trials. Data for four experimental trials were compared: (1) a work
      intensity set by experimenter to achieve a target RPE of 11 (Estimation 11), (2)
      an intensity set by experimenter to achieve a target RPE of 13 (Estimation 13),
      (3) an intensity varied by participant every 2 min. to produce a target RPE of 13
      (Production 13), and (4) a Step-up Procedure with the intensity varied by
      participant, first producing a target RPE of 11 during the first 2 min., followed
      by producing a target RPE of 13 from min. 2 to 6 of exercise (Production 11 +
      13). A very small effect size was found for HR between Production 13 and
      Estimation 13, and a moderate effect size was noted for the increased HR when
      patients produced a target RPE of 13 as compared to 11. The participants could be
      divided into 2 groups: 10 patients comprised a Higher group whose HR at 2 min.
      during Production 13 was greater than HR at 2 min. during Estimation 13, and 6
      patients in a Lower group with HR at 2 min. during Production 13 less than or
      equal to HR during Estimation 13. A large effect size was found at 6 min. for the
      reductions of the Higher group's HR overshoot and for the Lower group's HR
      undershoot during Production 13. All participants in the Higher group (n=10) had
      a clinically significant HR overshoot of 5 beats x min.(-1) at 2 min. during
      Production 13. Using a Step-up Procedure (Production 11 + 13), a large effect
      size was found for the reduced number of patients (n=3) with an overshoot of 5
      beats x min.(-1) at 2 min. This supports the ability of participants in cardiac
      rehabilitation programs to meet the Prescription Congruence and Intensity
      Discrimination components of the Intensity Self-regulation Model in the RPE 11-13
      zone. Evidence was found for overshoot/undershoot of target HR at 2 min.,
      supporting a proposed third component, Production Strategy, of the Intensity Self
      regulation Model. The 2-min. Step-up Procedure reduced some patients' tendency to
      "overshoot" target intensity.

PMID- 17450986
TI  - Validity and reliability of perceptually-based scales during exhausting runs in
      trained male runners.
AB  - The purposes of this study were to test the validity of a recent scale based on
      the estimation of a time of exhaustion (entitled Estimated Time Limit scale) to
      predict a time limit (Tlim) and to regulate exercise intensity and to investigate
      the reliability of the Estimated Time Limit scale and the Ratings of Perceived
      Exertion (RPE) scale. 14 male runners performed one incremental test, one
      constant velocity test at 85% of Maximal Aerobic Velocity (MAV), one constant
      duration test and one retest of 15 min. on an outdoor track. The difference
      between Estimated Time Limit values obtained during the incremental test at 85%
      MAV and measured Tlim values during the constant velocity test were examined, the
      velocities at ETL = 13 (i.e., 15 min.) obtained during the incremental test were
      compared with measured velocities during the constant duration test or the retest
      (only the best performance was used), and RPE and Estimated Time Limit values
      during the constant duration test were compared with those measured during
      retest. The results have shown a nonsignificant correlation between Estimated
      Time Limit values at 85% MAV and measured Tlim values during constant velocity
      test. There was a significant correlation (p < .02, r = .64) between velocities
      at ETL= 13 and measured velocities. However, the slope and y intercept value of
      this regression were significantly different from those of the identity line.
      There was no significant difference between constant duration test and retest for
      the values of RPE and Estimated Time Limit with high correlations (between r =
      .77 and .99 for RPE scale, and r = .74 and .99 for Estimated Time Limit scale).
      Moreover, the regression lines were close to the identity line. The RPE and
      Estimated Time Limit scales are reliable, but the lack of validity for the
      Estimated Time Limit scale suggests that more studies must be performed before
      using this scale to predict Tlim and regulate exercise intensity in male runners.

PMID- 17450987
TI  - Effect of pupil size on dynamic visual acuity.
AB  - This study was conducted to assess the effect of pupil size on dynamic visual
      acuity (DVA). 60 young healthy men (M = 28.1 yr., SD = 3.9) with normal vision
      were divided into three age-matched groups by pupil size: dilated (n=20),
      unchanged (n=20), and constricted (n=20). DVA was measured binocularly with
      freehead viewing before and at 30 min. after each drop was instilled. Each of the
      three groups got a different amount. The sizes of the constricted, unchanged, and
      dilated pupils were 2.8 mm (SD = 0.5), 4.1 mm (SD = 0.3), and 7.8 mm (SD = 0.5),
      respectively. The pupil size x DVA interaction was significant (F(2,114)= 6.07).
      DVA in the constricted pupil decreased, but that in the dilated pupil increased
      (paired t test). DVA in the unchanged pupil did not change significantly (paired
      t test). Pupil size is possibly one of the factors which may affect DVA
      measurement.

PMID- 17450988
TI  - Counting bones: environmental cues that decrease food intake.
AB  - At an all-you-can eat buffet in a sports bar, it was tested whether people would
      eat less if they knew how much they had already eaten. 50 graduate students (34
      women; M age = 24.1 yr.) were seated at 21 tables randomly assigned to be bussed
      (leftover wings removed) or unbussed (wings left on table). The 31 students at
      the bussed tables ate more than those at the unbussed tables (7 wings vs. 5.5
      wings), with the effect being stronger for men than women. In distracting eating
      environments, environmental cues may provide an effective means of reducing
      consumption. Implications for controlling alcohol intake were also noted.

PMID- 17450989
TI  - Morning and evening personality characteristics in a sample of young Italians.
AB  - The goal of this study was to investigate associations of morning and evening
      personality types with personality dimensions in a convenient sample of 60 men
      and 60 women, ages 18 to 29 years. A short form of the Morningness-Eveningness
      Questionnaire and a personality questionnaire Come mi vedo (How I see myself),
      based on the 5-factor model of personality, were given. Several personality
      dimensions appear to be significantly correlated with Morningness scores:
      Conscientiousness (positively) and Openmindedness (negatively). The analysis
      indicated morning types tend to reach their goals resolutely and to plan their
      steps, they prefer to be precise, tidy, punctual, trustworthy; they have a sense
      of duty and responsibility; they are also less original and less open to culture
      and novelties, less curious, conformist, traditionalist, and less well-informed,
      hardworking, steady, tenacious, and diligent, on the Come mi vedo.

PMID- 17450990
TI  - Practice evoking the flexor carpi radialis h-reflex: a guideline for proficiency.
AB  - The purpose of this research was to identify the number of sessions required for
      a new investigator to become proficient at evoking an H-reflex in the flexor
      carpi radialis (FCR), in comparison to an experienced investigator. 31 students
      from Brock University in the greater Niagara region (16 women M age = 32.2, SD =
      8.9 yr.; 15 men M age = 27.8, SD = 7.8 yr.) with no known neurological disorders
      volunteered and completed two test sessions performed by either an experienced or
      a novice investigator. In randomized order, both investigators stimulated each
      subject's median nerve 10 times, once every 15 sec. Each session included the
      measurement of the subject's flexor carpi radialis maximal M-wave amplitude and H
      reflex amplitude and latency with surface electromyographic electrodes. The
      intraclass correlation coefficients (ICC) indicated an adequate correlation
      between investigators for both M-wave maximal amplitude and H-reflex at 5% of the
      M-wave maximal amplitude (.84 and .70, respectively). However, there was a low
      correlation (.38) between the latency values obtained by the two investigators.
      The peak-to-peak amplitudes of the H-reflex and M-wave do not appear to be
      influenced by experience of the tester. The latency of the response, however,
      appears to have an associated learning curve, improving in consistency with
      increasing practice of tester.

PMID- 17450991
TI  - Is binocular fusion of "cortical yellow" an illusion, contingent upon abstraction
      of coherent sensory information from the two eyes?
AB  - This research on the binocular fusion of phenomenal yellow, given red-filtered
      flashes of light in one eye and green-filtered flashes of light in the other,
      directly compared the effects of wider-bandwidth and narrow-bandwidth filtering.
      20 male college students with normal stereopsis, Mage = 19.3 yr., SD = 2.2, were
      tested for the binocular perception of flashing yellow sensations given wider
      bandwidth versus narrow-bandwidth filtering of light flashes which, monocularly,
      were experienced as red sensations in one eye and as green sensations in the
      other. When 3 wide-bandwidth tests for binocular yellow fusion were alternated
      with 3 narrow-bandwidth tests, simultaneous flashes of red-filtered light in one
      eye and green-filtered light in the other were binocularly perceived as yellowish
      on 25% of the wide-bandwidth tests (SD = 40%)--as yellow on 8% of the tests,
      orange on 12% of the tests, yellow-green on 5% of the tests-and were binocularly
      perceived as yellowish on 0% of the narrow-bandwidth tests. When wider-bandwidth
      and narrow-bandwidth testing were separated spatially and conducted
      contemporaneously, the red-filtered flashes in one eye and green-filtered flashes
      in the other were binocularly experienced as yellowish sensations by 80% of all
      participants under wider-bandwidth conditions--as yellow by 55%, orange by 10%,
      yellow-green by 15%--and as yellowish sensations by 0% of the participants under
      narrow-bandwidth conditions.

PMID- 17450992
TI  - Listeners' cognitive and affective reactions to English speakers with standard
      American English and Asian Accents.
AB  - Using a 2 (speaker accent: standard American, Asian) x 2 (speakers' sex: male,
      female) between-subjects design, the present study examined the effects of accent
      and sex on listeners' cognitive and affective reactions towards speakers with
      standard American English accents and Asian accents. 70 female and 27 male
      college students (M = 21.8 yr., SD = 4.7) listened to the audio recording of a
      monologue by one of the speakers in the early 20s who differed in accent and sex.
      Standard American English was operationalized as nonaccented English, typical of
      the western part of the USA, and Vietnamese-accented English was used as an
      exemplar of Asian-accented English. Results showed that relative to standard
      American-accented English speakers, Asian-accented English speakers were
      perceived as poorer communicators who were less potent, less threatening, and
      more concerned about others. These cognitive reactions to Asian-accented English
      speakers include (a) the general stereotype associated with an accent, status and
      solidarity, as well as (b) the stereotype unique to Asians as an ethnic group,
      being concerned for others and poorer communicators. Analysis also showed that
      speakers with an Asian accent evoked more negative affect and required more
      attention from listeners than did speakers with a standard American English
      accent. Implications of the study are discussed.

PMID- 17450993
TI  - Postural movement pattern and muscle action sequence associated with self-paced
      bilateral arm flexion during standing.
AB  - Investigated were postural movement pattern and action sequence of postural
      muscles while subjects rapidly flexed both arms during standing. The arm movement
      was started at the subject's own pace. Subjects were healthy individuals; 48 men
      and 53 women. Postural movement pattern was classified based on the movement
      angles of foot-leg (ankle joint) and leg-trunk (hip joint). Electromyograms were
      recorded from the anterior deltoid, biceps femoris, and erector spinae. The time
      difference between action onsets of the latter two muscles and the anterior
      deltoid was analyzed. Movement angles of the ankle and hip for both sexes were
      distributed on a similar linear regression line (y = -2.092x - 2.552 (r = -.71).
      The postural movement pattern was categorized based on the distribution into
      three types: hip flexion (in the 2nd quadrant), backward leaning (the 3rd), and
      hip extension (the 4th). The proportion of subjects was 26% in the hip flexion
      type, 55% in backward leaning type, and 19% in hip extension type. The action of
      biceps femoris and erector spinae significantly preceded that of anterior deltoid
      in the backward leaning and hip extension types but did not in the hip flexion
      type.

PMID- 17450994
TI  - Morningness-eveningness correlates with verbal ability in women but not men.
AB  - Individuals differ along a continuum of preference for diurnal activity level,
      known as Morningness-Eveningness. Some evidence suggests that an Eveningness
      orientation (i.e., preference for later rise and bed times) is weakly associated
      with higher cognitive ability, but no studies have examined this relationship
      using clinically accepted, psychometrically valid measures of cognitive ability.
      The present study examined the correlation between Morningness-Eveningness with
      scores on the Wechsler Abbreviated Scale of Intelligence (WASI) of 54 healthy
      volunteers. Lower Morningness (i.e., Greater Eveningness) orientation was
      correlated (r = -.23) with higher Verbal IQ for the entire sample. When the data
      were examined separately by sex, the correlation between Morningness-Eveningness
      and Verbal IQ was significant for women (r = -.44) but not for men (r = -.09).

PMID- 17450995
TI  - Can cigarette warnings counterbalance effects of smoking scenes in movies?
AB  - Scenes in movies where smoking occurs have been empirically shown to influence
      teenagers to smoke cigarettes. The capacity of a Canadian warning label on
      cigarette packages to decrease the effects of smoking scenes in popular movies
      has been investigated. A 2 x 3 factorial design was used to test the effects of
      the same movie scene with or without electronic manipulation of all elements
      related to smoking, and cigarette pack warnings, i.e., no warning, text-only
      warning, and text+picture warning. Smoking-related stereotypes and intent to
      smoke of teenagers were measured. It was found that, in the absence of warning,
      and in the presence of smoking scenes, teenagers showed positive smoking-related
      stereotypes. However, these effects were not observed if the teenagers were first
      exposed to a picture and text warning. Also, smoking-related stereotypes mediated
      the relationship of the combined presentation of a text and picture warning and a
      smoking scene on teenagers' intent to smoke. Effectiveness of Canadian warning
      labels to prevent or to decrease cigarette smoking among teenagers is discussed,
      and areas of research are proposed.

PMID- 17450996
TI  - Adult attachment and declining birthrates.
AB  - Attachment scores for 658 young adults living in the U.S.A. were obtained using
      the Experiences in Close Relationships scale. The participants came from a
      subsample of the RELATE data set, who had also filled out the adult attachment
      measure. Those young adults living in Utah County, Utah, an area of the country
      with a higher than normal birthrate (88% members of the Church of Jesus Christ of
      Latter-day Saints), also had higher than average adult attachment scores. While
      the methodology was not sufficient to assess causal direction nor eliminate the
      possibility of unidentified influences, an undiscussed psychological factor,
      adult attachment, may play a role in the numerical declines observed among
      nonimmigrant communities in the USA and Europe.

PMID- 17450997
TI  - Correlations among executive function scales and positive psychological
      attributes in college students.
AB  - Scores on executive function scales were correlated with scores on attributes of
      positive psychology. Values were positive among gratitude, satisfaction, and the
      executive function scales of motivational drive, empathy, and strategic planning.
      If replicated and extended, such data may predict academic success in college
      students as in 13- to 14-yr.-olds.

PMID- 17450998
TI  - Personality in domestic cats.
AB  - Personality ratings of 196 cats were made by their owners using a 5-point Likert
      scale anchored by 1: not at all and 5: a great deal with 12 items: timid,
      friendly, curious, sociable, obedient, clever, protective, active, independent,
      aggressive, bad-tempered, and emotional. A principal components analysis with
      varimax rotation identified three intepretable components. Component I had high
      loadings by active, clever, curious, and sociable. Component II had high loadings
      by emotional, friendly, and protective, Component III by aggressive and bad
      tempered, and Component IV by timid. Sex was not associated with any component,
      but age showed a weak negative correlation with Component I. Older animals were
      rated less social and curious than younger animals.

PMID- 17450999
TI  - Who buys textbooks online: a replication.
AB  - In a study of 71 students, computer anxiety and computer/Internet skills
      predicted whether they purchased textbooks online.

PMID- 17451000
TI  - Are police officers more likely to kill African-American suspects?
AB  - In recent psychological research decisions by police officers to shoot criminal
      suspects are often assumed to be racially biased, and it is concluded that
      officers are more likely to shoot African-American suspects. This assumption was
      tested with national data on persons killed during legal interventions and with
      data bearing on the African-American proportion of criminal suspects law
      enforcement officers face. Analysis indicates that the African-American share of
      persons killed by law enforcement officers, while higher than the African
      American percentage of the U.S. population, is lower than one would expect based
      on the estimated African-American proportion of suspects confronted in violent
      encounters or the African-American percentage of suspects who kill police
      officers.

PMID- 17451001
TI  - Reliability and validity of Job Content Questionnaire in Chinese petrochemical
      employees.
AB  - To evaluate psychometric properties the Chinese (mainland) version of the 30-item
      Job Content Questionnaire was administered to 889 employees in 4 industries of
      PetroChina. A retest at 3 months with 296 randomly chosen employees showed
      reliabilities ranged from .76 to .93. Cronbach coefficients alpha for the 8
      dimensions ranged from .43 to .88, indicating that the Job Insecurity subscale
      had low internal consistency. Exploratory factor analysis showed 8 meaningful
      factors corresponding to the 8 theoretical dimensions of this questionnaire. This
      version has variable a but suitable retest to be a reliable and valid measure of
      job strain, applicable to the Chinese industrial working population of
      PetroChina.

PMID- 17451002
TI  - Content validity of the Visual Similes Test II.
AB  - This study examined the content validity of the Visual Similes Test II, designed
      to measure affective and cognitive arousal in individuals 5 to 21 years of age.
      The 54 participants were asked to rate the affective and cognitive content of
      unoccluded stimuli from the Visual Similes Test II. The participants, whose mean
      age was 27.0 yr. (SD=8.6), included 1 (2%) man and 53 (98%) women who were
      enrolled in undergraduate and graduate special education courses. Paired-sample t
      tests comparing the affective and cognitive ratings for each item were
      significant for 53 of the 55 stimuli. The mean effect size (Cohen d) was 1.49
      (range = .08 to 1.9).

PMID- 17451003
TI  - Some correlates of subjective life expectancy.
AB  - In samples of 193 American and 209 Kuwaiti college students, the correlates of
      subjective life expectancy differed in the two countries, a Tao orientation and
      existential anxiety in the American students and death anxiety in the Kuwaiti
      students.

PMID- 17451004
TI  - Important criteria for spouse selection in a sample of Iranian youth.
AB  - The aim was to study important criteria for spouse selection by a sample of
      Iranian youth, 110 Iranian university students (60 women and 50 men; M age = 21.7
      yr., SD = 1.5). Participants were single. Face-to-face interviews indicated that
      the order of the first 10 important criteria for the women were chastity,
      virtuous, religion, education, family characteristics, financial resources, job,
      commitment, social skills, and social prestige; for the men these were physical
      appearance, chastity, education, family characteristics, virtuous, religion,
      personality traits, social skills, housekeeping, and commitment and financial
      resources.

PMID- 17451005
TI  - Exploration of Thalbourne's Manic-Experience Scale.
AB  - The reliability of a 19-item scale to measure manic experience was explored in
      138 undergraduates. Cronbach alpha was .77, and five factors were identified,
      indicating heterogeneity in the items.

PMID- 17451006
TI  - An empirical study of some demographic and work-related variables on job
      satisfaction of academics in a Turkish university.
AB  - The Job Satisfaction Survey was administered to 610 faculty in a university in
      North Cyprus. As expected, job satisfaction increased with rank, and those who
      held administrative positions were more satisfied than staff who did not. The
      longer the participants had served in the current university, the higher their
      rated job satisfaction. Job satisfaction of women in higher academic positions
      was higher than that of their male peers. Age was not correlated with increases
      in job satisfaction.

PMID- 17451007
TI  - Social support at university scale, a brief index.
AB  - A brief, 3-item index of social support among college students, the Social
      Support at University Scale, is introduced. Its psychometric properties are
      examined in a sample of 90 college students (51 women, 39 men) and compared with
      those of an equivalent scale distributed among 100 university staff (67 women, 33
      men). The Short-Form Social Support Questionnaire, the Perceived Stress Scale,
      and the Hospital Anxiety and Depression Scale were also administered to each
      participant. The data suggest that the Social Support at University Scale
      possesses internal consistency reliability suitable for research (alpha = .68),
      external validity as indicated by comparisons between the student and staff
      samples, concurrent validity as indicated by correlations with measures of
      generic social support, and criterion validity as indicated by associations with
      known correlates of social support, namely, perceived stress, anxiety, and
      depression.

PMID- 17451008
TI  - Sense of authenticity, affectivity, and cultural construal of the self among
      Japanese university students.
AB  - This study examined the relationship between the sense of authenticity and
      affectivity, which is under the control of the cultural construal of the self.
      Japanese university students (N=287) rated themselves on the Sense of
      Authenticity Scale, the Positive and Negative Affect Schedule, and the Scale for
      Independent and Interdependent Construal of the Self. Analysis indicated that the
      Sense of Authenticity increased Positive Affect and decreased Negative Affect,
      regardless of the scores on Independent and Interdependent Self-construal.

PMID- 17451009
TI  - Japanese children's development of false belief understanding.
AB  - Two studies were conducted to examine the Japanese children's false belief
      understanding. Study 1, a small-scale meta-analysis that included 21 Japanese
      false belief studies yielding 60 data points, revealed that the Japanese
      children's false belief understanding develops with age (effect size = 2.48 in
      odds ratio for 1 year), the Japanese children's performance exceeds the chance
      level at the age of 64 months, and question type (think vs look-for) produced no
      statistically significant difference. An experiment (Study 2) employing a change
      of-locations task was conducted to confirm these findings, manipulating question
      type as a within-participant factor. Participants were 43 Japanese kindergartners
      (24 boys and 19 girls; 3 yr. 4 mo. to 6 yr. 1 mo.). The results showed that
      Japanese children's false belief performance developed with age. Their
      performance level exceeded the chance level at the age of 5 years, and question
      type did not affect their performance.

PMID- 17451010
TI  - Relations of low frustration tolerance beliefs with stress, depression, and
      anxiety in young adolescents.
AB  - Young adolescents (N=144; 66 boys, 78 girls), ages 12 to 14 years (M=12.2,
      SD=.8), who reported lower scores on the Low Frustration Tolerance Beliefs
      Instrument had higher scores on the Perceived Stress Scale and the Profile of
      Mood States Subscales of Depression and Anxiety.

PMID- 17451011
TI  - Perseveration of the partial reinforcement effect in extinction with rats over
      two phases of extinction and two stages of continuous reinforcement.
AB  - One group of 10 male albino rats was given partial reinforcement while the other
      10 rats received continuous reinforcement in a straight alley. Subjects then
      experienced five consecutive stages of Extinction 1, Continuous Reinforcement 1,
      Extinction 2, Continuous Reinforcement 2, and finally, Extinction 3. Analysis
      showed the partial reinforcement effect in extinction was sustained over two
      stages of extinction and two stages of continuous reinforcement, since subjects
      receiving partial reinforcement ran faster than rats given continuous
      reinforcement throughout all three of the extinction periods. The results seem to
      support those of Amsel's (1967) and Cabpaldi's (1967) theoretical formulations of
      the partial reinforcement effect in extinction.

PMID- 17451012
TI  - Relationship of IQ to suicide and homicide rate: an international perspective.
AB  - IQs were correlated with the z score of suicide rate minus z score of homicide
      rate using nine regions of the world--established market economies, formerly
      socialized Europe, India, China, other Asian nations, Sub-Saharan Africa, Latin
      America/Caribbean, Middle East Crescent, and the USA. Correlations were .85 and
      .83 with crude rates and age-adjusted rates, respectively. The homicide findings
      are consistent with previous research in individual countries showing that less
      intelligent persons commit homicide more often. However, the present findings of
      a positive correlation between IQ and suicide rates are the opposite of what has
      been found in the more definitive studies within countries. Explanations for the
      apparent paradox and for the findings more generally were offered.

PMID- 17451013
TI  - Adolescent personality and two measures of response inconsistency.
AB  - This study examined the relationship between the Response Inconsistency Scale
      (RINC) of the Adolescent Personality Questionnaire and the Variable Response
      Inconsistency Scale (VRIN) of the Minnesota Multiphasic Personality Inventory for
      Adolescents (MMPI-A) in a group of 62 participants. RINC and VRIN were positively
      correlated .30 (p < .01). Additionally, both scales were correlated with five
      broad personality scales available from the Adolescent Personality Questionnaire.
      Scores on both inconsistency scales correlated negatively with those on
      Extraversion, Independence, and Self-control (but the latter two not
      significantly).

PMID- 17451014
TI  - Digit ratio (2D:4D) in twins: heritability estimates and evidence for a
      masculinized trait expression in women from opposite-sex pairs.
AB  - The second-to-fourth digit ratio (2D:4D) is sexually dimorphic in humans, such
      that men on average have a lower 2D:4D than women. This somatic trait has been
      proposed as a biomarker for the organizational (permanent) effects of prenatal
      testosterone on the brain and behavior. Over the past few years, an accumulating
      research program has shown 2D:4D to be related to a multitude of sex-dependent,
      hormonally influenced psychological and behavioral traits. The present study
      investigated the 2D:4D ratio of 44 men and 70 women from 36 identical and 21
      fraternal twin pairs. Both basic and advanced approaches for estimating
      heritability concordantly suggested that the trait is substantially heritable.
      The best-fitting structural equation model indicated that the contributions to
      individual differences in 2D:4D are 81% additively genetic, 19% nonshared
      environmental, and 0% shared environmental. Supplemental analyses showed that,
      consistent with a prediction from sex-hormone transfer theory, women from
      opposite-sex fraternal twin pairs had significantly lower (more male-typical)
      2D:4D than women from same-sex fraternal twin pairs. Directions for research are
      discussed, such as investigating possible influences of the sex chromosomes on
      the expression of 2D:4D. Further family studies will be needed to test whether
      the transmission mode of 2D:4D is consistent with X-linked or Y-linked
      inheritance. The study of sex chromosome aberrations should indicate whether the
      presence of additional X or Y chromosomes is associated with 2D:4D levels.

PMID- 17451015
TI  - Perceived importance, enjoyment, and anxiety as correlates of computer attitudes.
AB  - A sample of 138 students was assessed for their computer attitudes using a Likert
      type questionnaire with three subscales: Computer Importance, Computer Enjoyment,
      and Computer Anxiety. An overall positive attitude towards computers was found.
      Multivariate analysis of variance revealed no significant differences in computer
      attitudes by gender although male students reported more positive attitudes
      towards computers than female students. Implications for educators include
      managing the perceptions of students that the computers are useful for learning
      purposes, in addition to using them for leisure and entertainment.

PMID- 17451016
TI  - Laying the foundations of well being: a creative psycho-educational program for
      young children.
AB  - Dysfunctional cognitive schemata and pessimistic explanatory styles are usually
      held responsible for some of the commonest features of depressed mood such as
      feelings of meaninglessness, resignation, and underachievement which seem to
      affect even young children. This pilot study investigates the applicability and
      efficacy of an interactive, creative psycho-educational program for preschoolers
      that aims at enhancing mastery and shaping optimistic explanatory styles. Twenty
      preschoolers participated in once-a-week hourly sessions which took place in
      their school and lasted for one school year. The intervention consisted of
      several playful tasks and novel creative activities specially designed to meet
      the needs and abilities of preschoolers, while satisfying the objectives of the
      school curriculum. The tasks were based on the principles of cognitive behaviour
      theory. Qualitative and quantitative analyses of our results support the efficacy
      of the intervention for preschoolers.

PMID- 17451017
TI  - College students' motivations for money and subjective well-being.
AB  - Previous research indicates that, while making money is important to college
      students, it is negatively correlated with subjective well-being. This study
      asked 157 undergraduate business and psychology students about the importance of
      making money, their motives for doing so, and several dimensions of subjective
      well-being: satisfaction with life, self-actualization, and mood/affect. Making
      money remains very important to college students. Being motivated to make money
      was not globally related to subjective well-being, but wanting to make money to
      help others, to feel secure, and to feel proud of oneself were predictive of
      happiness or subjective well-being. Motives such as comparing oneself favorably
      to others, spending impulsively, and overcoming self-doubt were not correlated
      with subjective well-being. Business students appeared more motivated to make
      money than other students and also to have more negative affect.

PMID- 17451018
TI  - Treatment of acute mania with ambient air anionization: variants of climactic
      heat stress and serotonin syndrome.
AB  - High concentrations of ambient anions (O2-) were used to augment treatment for 20
      acutely manic male patients. Anions were produced by an anion generator in a
      sealed room. A double-blind crossover design was used, and responses were
      evaluated with the Brief Psychiatric Rating Scale by 2 blinded raters. This
      produced a significant antimanic effect: total rating scores declined with anion
      treatment. Presham and postsham total scores for these 5 were 31.3 and 31.6,
      respectively. Pretreatment and posttreatment total scores were 31.6 and 26.3,
      respectively. Previous research indicates a role for serotonin in producing this
      antimanic effect.

PMID- 17451020
TI  - Preliminary examination of international students' adjustment and loneliness
      related to electronic communications.
AB  - Electronic communication, e.g., e-mail, internet, may facilitate international
      students' adjustment through contacts maintained in their native country. In the
      present study, the scores of 45 international students on a measure of adjustment
      and the Revised UCLA Loneliness Scale were significantly associated with their
      electronic communications involving their native country, but not with general
      internet or e-mail use. International students' scores on the Multigroup Ethnic
      Identity Measure were positively correlated with amount of contact with people in
      their native country but not with scores on measures of adjustment or loneliness.

PMID- 17451019
TI  - Topiramate attenuates a transient learning deficit after lesions inducing
      intracerebral hemorrhage.
AB  - 28 male Long-Evans rats prepared with lesions of the middle cerebral artery
      displayed deficits in spatial navigational learning in a simple version of the
      Morris Water Maze task not seen in animals prepared with the same injury but
      administered 4 treatments with topiramate after surgery.

PMID- 17451021
TI  - Improved advising ratings in an undergraduate psychology program.
AB  - During the late 1990s, the psychology department of Indiana University-Purdue
      University Indianapolis made investments in its undergraduate advising program in
      terms of additional professional personnel, a new orientation course, an
      experimental intrusive advising track, innovative peer activities, and expanded
      physical facilities. Against this backdrop of innovations, from 1995 to 2001 an
      exit survey of graduating seniors (N=311) showed improved evaluations of
      departmental counseling services. Ratings of the obtainability of advising on
      courses and the quality of course and career advising all showed significant
      upward shifts over the seven years of study. Regarding a specific innovation,
      students who completed a 1-hr. orientation course gave higher mean counseling
      ratings than those not enrolled.

PMID- 17451022
TI  - A study of the test of supervisory skills.
AB  - In supervisory selection and development it is important to assess individuals'
      supervisory competencies. In a field study, the Test of Supervisory Skills was
      validated against a surrogate criterion of supervisory performance, based upon
      position classification and supervisory experience. Subjects (N=2406), workers
      and applicants of both sexes, were recruited from multiple sources, tested, and
      the data analyzed to evaluate the usefulness of the test in human resource
      management applications. Both the current and prior results show significant
      relationships between scores on this test and various criteria of supervisory
      performance.

PMID- 17451023
TI  - Anhedonia and suicide: a 6.5-yr. follow-up study of patients hospitalised for a
      suicide attempt.
AB  - This was a prospective follow-up study of suicidal patients to assess the
      association of anhedonia, depression, and completed suicides. Survival analysis
      as well as Cox's regression makes it possible to weigh the influence of
      variables. A cohort of 106 patients (81 women, 25 men, M age=33 yr., SD=9.9)
      admitted to medical or surgical departments after a suicide attempt was followed
      during a 6.5-yr. mean observation period. In total, 6.7% of patients completed
      suicide. High proportion of male subjects (71.4%) and low anhedonia, assessed on
      the Physical Anhedonia Scale, decreased survival time of the cohort and
      characterized subjects who deceased by suicide. These results suggested that the
      people who completed suicide were characterized by low anhedonia. Further
      research is needed on people who attempt suicide and present with specific
      psychiatric diagnoses.

PMID- 17451024
TI  - Bioethical issues in biostatistical consulting: development of a survey.
AB  - To develop a survey, the Bioethical Issues in Biostatistical Consulting
      Questionnaire, for investigating bioethical issues in analysis, a comprehensive
      literature review was conducted to specify areas of bioethics. Through a focus
      group study and the evaluation by 10 biostatisticians, the questionnaire was
      constructed. Validation must involve a panel of experts. Now, test-retest
      reliability and factor analysis should be conducted on a group of eligible
      subjects.

PMID- 17451025
TI  - Implementing a pilot program of advanced directives in nursing homes.
AB  - This project focused on employing a comprehensive advance directive, called Five
      Wishes, that is suited to a process-oriented approach emphasizing a discussion of
      personal, social, and emotional needs in end-of-life care. With findings of a
      limited number of advance directives completed, the traditional explanation of
      the 'onset o f progressive deterioration' a mong the residents is offered.
      Residents wi th low sense of self-efficacy is suggested as another explanation
      and one worthy of further research.

PMID- 17451026
TI  - Conspiracy thinking and state-trait anxiety in young Polish adults.
AB  - The relationships among conspiracy thinking and state and trait anxiety were
      examined with 118 high school students who were assessed using the Conspiracy
      Beliefs Scale and the State-Trait Anxiety Inventory. Among boys there was a
      positive correlation between scores on A-Trait and the conspiracy thinking (r =
      .39) whereas among girls there was a negative correlation between these scores (r
      = -.32).

PMID- 17451027
TI  - Convergent and discriminant validity of the Marital Disillusionment Scale.
AB  - The Marital Disillusionment Scale, together with measures of divorce proneness,
      marital disaffection, work addiction, sensation seeking, intimacy, and marital
      satisfaction (using the subscales Marital Disharmony and Disaffection), was
      administered to 116 married people (42 men, 74 women) in a university town in the
      western USA. Scores on the Marital Disillusionment Scale had significant positive
      correlations with scores on the Marital Instability Scale (r = .54), the Marital
      Disaffection Scale (r = .72), and the two subscales Disharmony (r = .53) and
      Disaffection (r = .75) of the eMarital Satisfaction Inventory. Scores for the
      Marital Disillusionment Scale were negatively correlated with those for the
      Personal Assessment of Intimacy in Relationships Inventory (r = -.65) but were
      not significantly associated with scores for the Work Addiction Risk Test and the
      Brief Sensation Seeking Scale. The results support the convergent and
      discriminant validity of the Marital Disillusionment Scale.

PMID- 17451028
TI  - A proof for Rhiel's range estimator of the coefficient of variation for skewed
      distributions.
AB  - In this research study is proof that the coefficient of variation (CV(high-low))
      calculated from the highest and lowest values in a set of data is applicable to
      specific skewed distributions with varying means and standard deviations. Earlier
      Rhiel provided values for d(n), the standardized mean range, and a(n), an
      adjustment for bias in the range estimator of micro. These values are used in
      estimating the coefficient of variation from the range for skewed distributions.
      The d(n) and an values were specified for specific skewed distributions with a
      fixed mean and standard deviation. In this proof it is shown that the d(n) and an
      values are applicable for the specific skewed distributions when the mean and
      standard deviation can take on differing values. This will give the researcher
      confidence in using this statistic for skewed distributions regardless of the
      mean and standard deviation.

PMID- 17451029
TI  - Between-group differences and taxometrics.
AB  - In psychological research it can be of interest to differentiate between the
      categorical (taxonic) vs dimensional (nontaxonic) nature of phenomena, for
      example in the field of psychopathology. For categorical (taxonic) structures a
      further differentiation is possible: between categorical structures with
      dimensional equivalence and a substantial main effect, and structures without
      dimensional equivalence (independent of the main effect). Previous taxometric
      studies have not concentrated in an explicit way on the case of nonequivalence.
      It is shown here that under favorable circumstances both types of categorical
      structures can be detected using the taxometric procedure L-Mode, but that they
      cannot be differentiated from one another.

PMID- 17451030
TI  - Self-perception of the antecedents of loneliness among new mothers and pregnant
      women.
AB  - This study examined the perceived causes of loneliness of pregnant women and
      mothers during the first year after childbirth experience. These were compared
      with the causes of loneliness of women in the general population. 91 pregnant
      women, 97 women during the first year following childbirth, and 208 women from
      the general population (M age = 30.4, SD = 10.4) answered a 29-item Loneliness
      Antecedents Questionnaire. In the questionnaire were 5 dimensions of sources of
      loneliness, namely, Personal Inadequacies, Developmental Deficits, Unfulfilling
      Intimate Relationships, Relocation/Significant Separation, and Social
      Marginality. Sources of loneliness were significantly different amongst the three
      groups. The differences were confined to the Personal Inadequacies, and the
      Relocation/Significant Separation subscales. In both, women from the general
      population had the highest mean subscale scores.

PMID- 17451031
TI  - On measuring time metaphors.
AB  - Referring to the 2005 article by Wittmann and Lehnhoff, the problem of using time
      metaphors for measuring awareness of time is posed. Starting from clarification
      of meaning, the Metaphors Slowness scale which was not homogeneous, an
      alternative interpretation of the result was proposed, given that metaphors refer
      to two separate aspects of time speed, an ongoing passage of time, and ex post
      reflection on passage of time that has already passed. The former refers to the
      judgment of an ongoing passage of time, and the latter to the judgment of passage
      of past time from a particular point in the past till now. Time perception is
      multifaceted and perhaps ambiguous. This particular aspect of time perception is
      covered by a notion of a "dialectical time", when opposite aspects of time are
      combined, e.g., pleasant and unpleasant ones.

PMID- 17451032
TI  - Eyewitness misidentification: single vs. double-blind comparison of photospread
      administration.
AB  - Interactive effects of photospread procedures (blind administration or has
      knowledge of suspect identity) and presentation techniques (sequential or
      simultaneous photospreads) on false eyewitness identification rates were
      examined. Of 117 subjects (57 men and 60 women), 87 served as a witness sample
      and 30 as a photospread administrator sample. Witnesses viewed a 20-sec. mock
      robbery video prior to viewing a photospread of six photographs either
      simultaneously or sequentially. Half of the administrators, prior to displaying
      the photospreads, were made aware of the photograph of the designated suspect
      (single-blind condition). Consistent with previous findings, sequential
      presentation was associated with both lower overall false identification rates as
      well as lower suspect designated-misidentification rates. In each case, there was
      evidence that administrators' knowledge increased false identification rates more
      in simultaneous than in sequential presentation conditions. Implications for
      administrations by police investigators are discussed.

PMID- 17451033
TI  - Two-sample multivariate similarity permutation comparison.
AB  - A multivariate permutation test of similarity between two populations with
      corresponding unordered disjoint categories is described. The test statistic,
      resampling probability value, and measure of effect size are described.

PMID- 17451034
TI  - Naloxone decreases responding for conditioned reinforcement in rats.
AB  - That opioids can mediate unconditioned reinforcement is well established, but
      there is little evidence indicating whether they modify conditioned
      reinforcement. Here, a tone which initially served as a discriminative stimulus
      for the availability of water reinforcement was established as a conditioned
      stimulus. When later given a choice between pressing a lever producing the tone
      (but not water) or one which produced no effect, rats chose the tone-producing
      lever 66% of the time. Naloxone (3.0 mg/kg) reduced overall responding and
      completely eliminated the preference for the tone-producing lever. Results are
      briefly discussed in terms of the importance of understanding mechanisms serving
      conditioned reinforcement.

PMID- 17451035
TI  - Importance of goal setting in virtual project teams.
AB  - This research investigated goal setting on engineering teams with geographically
      dispersed members. A survey was designed to measure the Quality of Goal Setting,
      Goal Commitment, Perceived Task Outcomes, and Perceived Psychosocial Outcomes,
      all constructs and scales used in previous research on project teams. 82
      respondents from 12 virtual teams participated. Analysis suggested the quality of
      goal setting affected Perceived Task Outcome (t = 2.40, p < .05) but not
      Perceived Psychosocial Outcomes. Further regression analysis indicated goal
      commitment predicted significant variance in both Perceived Task Outcomes (t =
      2.35, p < .05) and Perceived Psychosocial Outcomes (t = 4.3, p < .01). These
      results suggest that setting high quality goals and building commitment to goals
      significantly affect perceptions of outcomes on virtual project teams.

PMID- 17451036
TI  - Effects of delay on color priming for natural objects.
AB  - Using a standard study-test procedure, color priming was examined through effects
      of color transformation, from correctly colored to incorrectly colored and vice
      versa, for natural objects with pre-existing color-shape associations, e.g.,
      yellow banana. More specifically these effects were examined at study-test delays
      of 0, 24, and 48 hr. When deciding whether an object was correctly colored, color
      transformation eliminated priming. Furthermore, there was evidence that for
      objects that were not transformed, priming was stronger for correctly as compared
      with incorrectly colored objects. In addition, the introduction of 24- and 48-hr.
      delays between the study and the test phase of the task reduced the effects of
      color transformation on priming. These findings are discussed in terms of the
      representations that mediate implicit memory performance.

PMID- 17451037
TI  - Lifestyle behaviors and mental health of American adults.
AB  - The purpose of this study was to test the hypothesis that individuals reporting
      healthy lifestyle behaviors would also report better self-rated mental health.
      Logistic regression analyses were conducted utilizing SUDAAN on the Behavioral
      Risk Factor Surveillance Survey data set. This descriptive analysis suggests that
      persons reporting poor mental health were more likely to report unhealthy
      lifestyle behaviors. This set of findings encourages careful design of
      experimental studies of empirically based associations of mental health and life
      style, using psychometrically sound measures. Then public health programs focused
      on change of health-related behaviors might be more suitably devised.

PMID- 17451038
TI  - Are complex psychotherapies more effective than biofeedback, progressive muscle
      relaxation, or both? A meta-analysis.
AB  - A meta-analysis of 26 studies was conducted to assess whether more complex forms
      of psychotherapy would be superior to control treatments of either biofeedback,
      progressive muscle relaxation, or both. Consistent with hypotheses, more complex
      treatments provided a small, significant improvement over biofeedback and
      progressive muscle relaxation (r = .09). A subset of the more complex behavioral
      treatments accounted for most of this small incremental effectiveness of more
      complex treatments (r = .15). Possible sources of this incremental effectiveness
      are discussed.

PMID- 17451039
TI  - Attitudes of university students towards people with paranoid schizophrenia.
AB  - To study attitudes towards persons with paranoid schizophrenia of first- and
      final-year university students taking three different majors, Link's Social
      Distance Scale, modified to relate to several vignettes presenting different
      descriptions of a patient with paranoid schizophrenia, was administered to 617
      university students ages 18 to 29 years (M = 21.1, SD = 2.6). 423 were women and
      194 men. Analysis indicates fourth year psychology majors reported the greatest
      acceptance of persons with paranoid schizophrenia. The most efficient vignette in
      diminishing rejection of the portrayed patient included information on the
      patient's psychosocial rehabilitation status. University students' attitudes
      appear to vary with the training they receive and the kind of information they
      have about the patient.

PMID- 17451040
TI  - Preliminary evidence for validity of the Bahasa Indonesian version of Study
      Process Questionnaire.
AB  - This study provides preliminary evidence for the validity of the Bahasa
      Indonesian version of the Study Process Questionnaire (BI-SPQ) from a sample of
      147 psychology students (22 men and 125 women; M age = 21.8 yr., SD = 1.3). The
      internal consistency alpha of the BI-SPQ subscales were found to range from .46
      (Surface Strategy) to .77 (Deep Strategy), with a median of .67. Principal
      component analysis indicated a two-factor solution, where the Deep and Achieving
      subscales loaded onto Factor 1 and the Surface subscales loaded on Factor 2.
      Students' GPAs were associated negatively with Surface Motive (r = -.24) and were
      associated positively with Deep and Achieving Motives (rs = .20). Further studies
      with larger samples involving students majoring in other disciplines are needed
      to provide further evidence of the validity of the BI-SPQ.

PMID- 17451041
TI  - Life-history related differences in possible selves in very old age.
AB  - The impact of early life events that take place under specific historical and
      societal circumstances on adult development have rarely been investigated in old
      age. We examined whether having started a family in young adulthood was related
      to the contents of possible selves generated by women aged 85 to 100+ in the
      Berlin Aging Study (N = 129; M age = 93 years). Health-related possible selves
      dominated in the entire sample. However, mothers (n = 79) and lifetime childless
      women (n = 50) differed in their endorsement of family- and friend-related
      possible selves. Contrary to expectations, childless women mentioned more family
      related themes, while mothers addressed more friendship-related themes. Despite
      these differences both groups of women reported equally high levels of well
      being. These findings indicate that starting a family in young adulthood still
      has an influence on the self up until very old age and that these distinct
      pathways can still lead to similar aging success.

PMID- 17451042
TI  - Is there life without work?
AB  - The present study examined the way retirees perceive retirement and continue to
      work post-retirement. Using a longitudinal design, qualitative and quantitative
      analyses were performed to examine the effect of preoccupation with work on
      adjustment to retirement. The findings indicate a wide range of attitudes toward
      cessation of the working life on the eve of retirement. In addition, most
      retirees reported increased well-being and decreased distress one year after
      retirement. Although for all participants a correlation was found between
      adjustment and preoccupation with work on the eve of retirement, no difference in
      the adjustment measures emerged a year later between those who were fully retired
      and those who continued to work. The implications of the findings for both
      personal well-being and social policy are discussed.

PMID- 17451043
TI  - Reminiscence and vivid personal memories across adulthood.
AB  - This study examined reminiscence functions and vivid (i.e., landmark) personal
      memories in nine samples ranging from the teens to the nineties. Participants (n
      = 198) ranging in age from 18-95 years completed the Reminiscence Functions Scale
      (Webster, 1997) and described a vivid personal memory which was subsequently
      rated for frequency of recall, emotional valence, time of occurrence, impact, and
      thematic content. Reminiscence results showed that older adults tend to
      reminiscence more for social functions while younger adults tend to reminisce
      more for self functions. Older adults reported vivid memories that were less
      intimate and less negative although adults of all ages showed the "reminiscence
      bump." Significant relationships were also obtained between the content of vivid
      memories described and the patterns of general reminiscence behaviors.

PMID- 17451044
TI  - Age differences in types of interpersonal tensions.
AB  - This study examined age differences in topics that generate interpersonal
      tensions as well as relationship level characteristics that may account for
      variability in the content of interpersonal tensions. Participants aged 13 to 99
      years (N = 184) diagramed their close and problematic social networks, and then
      provided open-ended descriptions of recent tensions with up to 6 social partners.
      Multilevel models were conducted to examine variability in 5 types of tensions
      (i.e., financial issues, daily activities, scheduling, job/school, and self).
      Older adults were less likely than younger ages to describe tensions over
      job/school and daily activities. Job/school tensions were more likely to occur
      with acquaintances and negative network members. Tensions over scheduling were
      more likely to occur with positive and ambivalent network members, and tensions
      over daily activities were associated with less emotional distress. Results
      suggest relationship characteristics contribute to the content of tensions.

PMID- 17451045
TI  - Fine structure of the area subpostrema in rat. Open gate for the medullary
      autonomic centers.
AB  - The area subpostrema (ASP) is a V-shaped area, ventral and ventrolateral to the
      area postrema. It constitutes the upper border zone of the commissural portion of
      the nucleus of the solitary tract. The ASP is considered as a morphological and
      functional key area for the medullary autonomic center. The capillaries here, in
      contrast to the capillaries of the area postrema are not fenestrated but
      establish a specific staining for acetylcholinaestherase (AChE). The ASP contains
      a high density of fibers and terminals of several neuropeptides which are known
      to affect on NTS activity. Receptors of different neuropeptids and
      cathecholamines and a dense network of GFAP positive glial processes are found
      also here. The neurons and the glial cells of the ASP are connected with the AP
      and a bidirectional connection exists between the ASP and NTS.

PMID- 17451046
TI  - Projections of VIP/PHI neurons of the interstitial nucleus of Cajal in the rat.
AB  - Neurons expressing VIP/PHI precursor mRNA have been localized in the interstitial
      nucleus of Cajal. Unilateral surgical cut through the medial forebrain bundle
      failed to influence VIP/PHI mRNA expression in the Cajal nucleus while brainstem
      hemisection or unilateral transection of the medial longitudinal fascicle reduced
      it markedly, ipsilateral to the knife cuts. Thus, in contrast to forebrain
      projecting VIP neurons in the rostral periaqueductal gray, VIP/PHI neurons in the
      Cajal nucleus project downwards, to the lower brainstem.

PMID- 17451047
TI  - Pituitary atrial natriuretic peptide of paraventricular nucleus origin.
AB  - Atrial natriuretic peptide-synthesizing neurons in the hypothalamic
      paraventricular nucleus constitute the major sources of ANP in the three lobes of
      the pituitary gland. Complete transection of the pituitary stalk eliminated 93%
      of ANP from the intermediate lobe, 47 and 77% from the anterior and the posterior
      lobes, respectively. Meantime, increased levels of immunoreactive ANP were
      measured in the median eminence, due to the accumulation of the peptide in the
      transected axons centrally to the transected stalk and in the paraventricular
      nucleus. It is likely that ANP neurons in the paraventricular nucleus innervate
      the pituitary, but those in the periventricular (median) preoptic nucleus and the
      organum vasculosum laminae terminalis may not contribute to the ANP innervation
      of the pituitary gland.

PMID- 17451048
TI  - Brain insulin signalling in the regulation of energy balance and peripheral
      metabolism.
AB  - The unparalleled global rates of obesity and type 2 diabetes, together with the
      associated cardiovascular morbidity and mortality, are referred to as the
      "diabesity pandemic". Changes in lifestyle occurring worldwide, including the
      increased consumption of high-caloric foods and reduced exercise, are regarded as
      the main causal factors. Central obesity and insulin resistance have emerged as
      important linking components. Understanding the aetiology of the cluster of
      pathologies that leads to the increased risk is instrumental in the development
      of preventive and therapeutic strategies. Historically, skeletal muscle, adipose
      tissue and liver were regarded as key insulin target organs involved in insulin
      mediated regulation of peripheral carbohydrate, lipid and protein metabolism. The
      consequences of impaired insulin action in these organs were deemed to explain
      the functional and structural abnormalities associated with insulin resistance.
      The discovery of insulin receptors in the central nervous system, the detection
      of insulin in the cerebrospinal fluid after peripheral insulin administration and
      the well-documented effects of intracerebroventricularly injected insulin on
      energy homeostasis, have identified the brain as an important target for insulin
      action. In addition to its critical role as a peripheral signal integrating the
      complex network of hypothalamic neuropeptides and neurotransmitters that
      influence parameters of energy balance, central nervous insulin signalling is
      also implicated in the regulation of peripheral glucose metabolism. This review
      summarizes the evidence of insulin action in the brain as part of the
      multifaceted circuit involved in the central regulation of energy and glucose
      homeostasis, and discuss the role of impaired central nervous insulin signalling
      as a pathogenic factor in the obesity and type 2 diabetes epidemic.

PMID- 17451049
TI  - Effects of ketamine on the developing central nervous system.
AB  - Ketamine is a widely used drug in pediatric anesthesia practice, acting primarily
      through the blockade of the N-methyl-D-aspartate (NMDA) type of glutamate
      receptors. A growing body of laboratory evidence, accumulated during the past few
      years, suggests that this drug could have potential adverse effects on the
      developing central nervous system. The goal of this short review is to give a
      brief synopsis of experimental work indicating ketamine-induced developmental
      neurotoxicity as well as to discuss potential limitations concerning
      extrapolation of these studies to clinical practice.

PMID- 17451050
TI  - The ghrelin system: physiopathological involvement in the control of body growth
      and energy metabolism.
AB  - This short review will summarize some recent findings on the physiopathology of
      the endogenous ghrelin/obestatin system by focussing on experimental studies
      aiming at blocking the effects of endogenous ghrelin and clinical studies
      investigating genotype/phenotype correlations concerning the genes encoding for
      ghrelin and its cognate receptor.

PMID- 17451051
TI  - Human trypsin(ogen) 4-like immunoreactivity in the white matter of the cerebral
      cortex and the spinal cord.
AB  - Human brain trypsin(ogen) 4-like (HT-4) immunoreactivity was localized in glial
      cells of human cerebral cortex and spinal cord. After a short post mortem delay
      (two hours), cortical and spinal cord regions were dissected, frozen or immersed
      into a fixative solution. Sections of 10 and 50 microm thickness were cut and
      immunostained by antibodies raised against recombinant human trypsin 4. HT-4-like
      immunoreactive glial cells and fibers were stained in the white matter, low to
      moderate levels of immunostaining were also observed in the matrix of the
      cerebral cortex and the spinal cord. To characterize HT-4-like immunopositive
      glial cells, alternate sections were immunostained for astrocytes and
      oligodendrocytes. HT-4 is present predominantly in astrocytes, but some of the
      oligodendrocytes and microglial cells may also contain this enzyme.

PMID- 17451052
TI  - Using brain slice cultures of mouse brain to assess the effect of growth factors
      on differentiation of bone marrow derived stem cells.
AB  - Bone marrow derived stem cells (BMDSCs) have been reported to form neurons and
      supportive cells in the brain. We describe a technique that combines the
      simplicity of in vitro studies with many of the advantages of in vivo
      experiments. We cultured mouse brain slices, deposited GFP-tagged BMDSCs evenly
      distributed on their surfaces, and then added test factors to the culture medium.
      Addition of both SDF-1 and EGF resulted in morphological changes of BMDSC and in
      the induction of islet-1, a marker of neuroepithelial progenitors. We conclude
      that organotypic tissue culture (OTC) may allow us to detect the effects of
      exogenous factors on the differentiation of BMDSCs (or any other type of stem
      cells) in an environment that may resemble the CNS after brain injury. Once such
      factors have been identified they could be evaluated for tissue regeneration in
      more complex, whole animal models.

PMID- 17451053
TI  - Central atrial natriuretic peptide in dehydration.
AB  - To test the effect of dehydration on brain atrial natriuretic peptide (ANP)
      concentrations in areas important to salt appetite, water balance and
      cardiovascular regulation, we subjected rats to dehydration and rehydration and
      measured ANP concentration in 18 brain areas, as well as all relevant peripheral
      parameters. Water deprivation decreased body weight, blood pressure, urine
      volume, and plasma ANP, while it increased urine and plasma osmolality,
      angiotensin II, and vasopressin. ANP greatly increased in 17 and 18 brain areas
      (all cut cerebral cortex) by 24 h. Rehydration for 12 h corrected all changes
      evoked by dehydration, including elevated ANP levels in brain. We conclude that
      chronic dehydration results in increased ANP in brain areas important to salt
      appetite and water balance. These results support a role for ANP as a
      neuroregulatory substance that participates in salt and water balance.

PMID- 17451054
TI  - Activated somatostatin type 2 receptors traffic in vivo from dendrites to the
      trans-golgi network.
AB  - BACKGROUND AND PURPOSE: Understanding the trafficking of G-protein-coupled
      receptors is of particular importance. In the central nervous system, although
      some G-protein-coupled receptors were reported to internalize in vivo, little is
      known about their trafficking downstream of the endocytic event. METHODS: The
      distribution of the major somatostatin receptor subtype, the sst2, was monitored
      in the hippocampus using immunofluorescence from 10 minutes to seven days after
      in vivo injection of the receptor agonist octreotide. RESULTS: From 10 min to 3 h
      after agonist injection, intensity of receptor immunoreactivity gradually
      decreased in the molecular layer of dentate gyrus and in the strata oriens and
      radiatum of CA1. Concomitantly, in the granular and pyramidal layers, small
      spherical immunofluorescent particles became apparent in perikarya, shortly after
      agonist stimulation (i.e. 30 min, 60 min). After longer survival times (i.e. 3 h,
      6 h, 24 h), immunolabeling was confined to larger, intensely-stained
      intracytoplasmic vesicles. From 48 h to 7 d after agonist injection, distribution
      and intensity of sst2 receptor immunoreactivity became similar to that of control
      animals. The sst2 receptor labeling extensively colocalized with TGN38 and
      syntaxin 6 after OCT injection. Colocalization with trans-Golgi markers was
      observed as soon as 1 h after OCT injection and still present 24 h after. By
      contrast, colocalization with the endoplasmic reticulum marker PDI and the cis
      Golgi marker GM130 was never observed. CONCLUSIONS: Our results suggest that upon
      agonist stimulation, dendritic receptors are retrogradely transported to a trans
      Golgi network domain enriched in the t-SNARE syntaxin-6 and TGN38 proteins before
      recycling.

PMID- 17451055
TI  - Oxygen-glucose deprivation-induced changes in organotypic cultures of the rat
      hippocampus.
AB  - INTRODUCTION: (-)Deprenyl is an irreversible inhibitor of type B monoamine
      oxidase (MAO-B), which is now used for treatment of Parkinson's or Alzheimer's
      diseases. Evidence suggests that the neuroprotective effect of deprenyl may not
      be related exclusively to the inhibition of the enzyme MAO-B. METHODS: To test
      the impact of deprenyl on ischemia-induced changes in vitro, we followed the time
      course of propidium iodide (PI) uptake as an indicator of neuronal cell death as
      well as the expression of apoptotic factors in organotypic hippocampal slice
      cultures exposed to oxygen-glucose deprivation (OGD) for 45 min. RESULTS: The
      first signs of neuronal death were detected 2 hours after OGD and were extended
      to all subfields of the hippocampus by 24 hours post-injury. Presence of deprenyl
      (10(-9) M) significantly delayed the cell death induced by the insult. Exposure
      of control cultures to deprenyl significantly increased the abundance of Bcl-2
      and Bcl-xl mRNAs as revealed by RT-PCR. OGD resulted in an elevation of anti
      apoptotic factors, while the expression of pro-apoptotic bax remained unchanged.
      CONCLUSION: These data suggest that deprenyl is neuroprotective in an in vitro
      model of ischemia. Although deprenyl upregulates the expression of Bcl-2 under
      basal conditions, its effect on anti-apoptotic factors is not significantly
      manifested during OGD.

PMID- 17451056
TI  - Postnatal expression pattern of doublecortin (DCX) in some areas of the
      developing brain of mouse.
AB  - We have investigated the spatio-temporal expression pattern of doublecortin (DCX)
      protein from postnatal day (P) 2 to postnatal day (P) 22 in the brain of
      developing mouse. We compared the expression of DCX in the rostral migratory
      stream (RMS) and dentate gyrus of the hippocampus (DG). Weak expression of DCX
      was detected in the RMS at P5, it became gradually stronger during the second
      postnatal week and reached its strongest expression by P18-P22. Moderate DCX
      immunostaining was present in the DG at P11, its marked expression-
      characteristic of newly generated neurons in the adult DG -appeared only after
      P22. Morphological and functional maturation was different in the RMS and DG,
      continuous neurogenesis appeared earlier in the RMS than in the DG.

PMID- 17451057
TI  - Protective action of snake venom Naja naja oxiana at spinal cord hemisection.
AB  - Based on data accumulated regarding the neuroprotective action of Proline-Rich
      Peptide-1 (PRP-1, a fragment of neurophysin vasopressin associated hypothalamic
      glycoprotein consisting of 15 amino acid residues) on neurons survival and axons
      regeneration and taking into the account that LVV-Hemorphin-7 (LVV-H7, an opioid
      peptide, widely distributed in different cell types of various tissues of intact
      rats, including those of the nervous and immune systems) derived from the
      proteolytic processing of hemoglobin in response to adverse environmental and
      physiological conditions, possesses the anti-stressor properties, we used
      histochemistry, immunohistochemistry and electrophysiology to investigate the
      putative neuroprotective action of Central Asian Cobra Naja naja oxiana snake
      venom (NOX) on trauma-injured rats. ABC immunohistochemical method and
      histochemical method on detection of Ca2+-dependent acid phosphatase activity
      were used for the morpho-functional study. By recording the electrical activity
      of the signals from the single neurons in and below the SC injury place, NOX
      venom has been shown to result in the complete restoration of hypothalamic-spinal
      projections originated from ipsi- and contra-lateral PVN and SON to neurons of SC
      lumbar part. NOX prevented the scar formation, well observed two months after SC
      injury in the control rats, resulted in the regeneration of nerve fibers growing
      through the trauma region, survival of the PRP-1- and LVV-H7-immunoreactive (Ir)
      neurons, and increase of the PRP-1 - and LVV-H7-Ir nerve fibers and astrocytes in
      the SC lesion region. NOX was suggested to exert the neuroprotective effect,
      involving the PRP-1 and LVV-H7 in the underlying mechanism of neuronal recovery.

PMID- 17451058
TI  - Optimal Alignment novel software procedure for 3D reconstruction of
      electronmicroscopic serial sections.
AB  - 3D reconstruction from electronmicroscopic (EM) serial sections substantially
      differs from modeling body parts by linking convoluted planes delivered by CT and
      NMR. Namely, variations both in relative X-Y position and rotation of the target
      elements between the adjacent images and also additional problems caused by
      deformed, deteriorated or missing sections can only be overruled by an aligning
      paradigm, which exploits all the pixel-level information, and results in an
      optimal fitting with selected precision. This paper presents a complex computer
      program called Optimal Alignment, which performs the precise elaboration of X-Y
      shift and relative rotation of two consecutive images. The required searching
      process will be customized by setting four independent parameters which relate
      the span and density of the pixel-scanning basic process. Optimalization of
      fitting accuracy versus running time can be achieved by a rather short training
      period. The potential precision of Optimal Alignment based on complex algorithms
      is far superior to manual aligning of EM photographs with the eye-wrist-mouse
      facility. The resulted database of alignment orientation parameters can serve as
      an advanced source for the 3D reconstructing programs. Optimal Alignment software
      tool (supported by Hungarian Space Office grant TP 138) will be demonstrated on a
      basal forebrain NPY+ axonal reconstruction, performed in L. Zaborszky's
      laboratory (supported by NIH grant NSO23945).

PMID- 17451059
TI  - The supraspinal innervation of the left adrenal is more intense than that of the
      right one.
AB  - BACKGROUND AND PURPOSE: Previous studies using the viral transneuronal tracing
      technique demonstrated that central autonomic circuits are involved in the
      innervation of the adrenal gland. Since increasing number of data indicate
      laterality in the neuroendocrine system, we aimed to investigate whether the
      supraspinal innervation of the adrenal gland exhibits asymmetry or not. METHODS:
      The central circuitry involved in the innervation of the left and the right
      adrenal gland was studied in individual rats by dual transneuronal tracing using
      isogenic recombinant strains (BDG and BDL) of Bartha strain of pseudorabies
      virus. RESULTS: Viral infection of brain nuclei (dorsal vagal nucleus, nucleus of
      the solitary tract, caudal raphe nuclei, A5 cell group, hypothalamic
      paraventricular nucleus) from the left adrenal was more severe than that from the
      right organ. Dual-infected neurons from the two adrenals were also detected both
      in the brain stem and in the hypothalamus. CONCLUSION: The results indicate a
      predominance in the supraspinal innervation of the left adrenal gland. Data
      further suggest that each adrenal gland is innervated both by side-specific
      neurons and by neurons which project to both organs.

PMID- 17451060
TI  - Salsolinol and the peripheral sympathetic activity: the effects of
      hypophysectomy, adrenalectomy and adrenal medullectomy.
AB  - The endogenous isoquinoline salsolinol (SALS) is a recently identified prolactin
      (PRL) releasing factor, a selective and potent stimulator of PRL secretion both
      in vivo and in vitro. SALS decreased the peripheral tissue dopamine (DA) level
      dose dependently, consequently increased the NE/DA ratio, indicating reduced
      release of newly formed norepinephrine (NE) from sympathetic terminals. The aim
      of our study was to investigate the effect of adrenal medullectomy (MEDX),
      adrenalectomy (ADX) and hypophysectomy (HYPOX) on the action of SALS on the PRL
      secretion, and on the catecholamine concentration of the selected sympathetically
      innervated peripheral tissues (atrium, spleen, etc). The experiments were done in
      male rats of 200-300 g body weight kept in air conditioned room with regular
      lighting. We used high-pressure liquid chromatography with electrochemical
      detection (HPLC-EC) for measurement of NE and DA concentrations, and
      radioimmunoassay for prolactin measurement. In MEDX as well as in ADX rats, SALS
      (25 mg/kg i.p.) was able to reduce DA level and increase the NE/DA ratio. The
      changes of prolactin secretion (increase by SALS) were not affected either by ADX
      or MEDX. Therefore the presence of the adrenal gland is not required for the
      changes of prolactin secretion, nor for the reduction of peripheral sympathetic
      activity induced by SALS. Investigating the possible effect of pituitary hormones
      on the peripheral sympathetic system, the action of SALS has been tested in HYPOX
      rats. We have found that the effect of SALS on peripheral sympathetic terminals
      is not affected by HYPOX, consequently the role of pituitary hormones in the
      effect of SALS on the peripheral catecholamine metabolism may be excluded.

PMID- 17451061
TI  - Synaptic connections of glutamatergic nerve fibres in the rat suprachiasmatic
      nucleus.
AB  - BACKGROUND AND PURPOSE: The hypothalamic suprachiasmatic nucleus functioning as
      the principal circadian pacemaker in mammals, has a rich glutamatergic
      innervation. Nothing is known about the terminations of the glutamatergic fibres.
      The aim of the present investigations was to study the relationship between
      glutamatergic axon terminals and vasoactive intestinal polypeptide (VIP), GABA
      and arginine-vasopressin (AVP) neurons in the cell group. METHODS: Double label
      immunocytochemistry was used and the brain sections were examined under the
      electron microscope. Vesicular glutamate transporter type 2 was applied as marker
      of the glutamatergic elements. Results - Glutamatergic fibers were detected in
      synaptic contact with GABAergic, VIP- and AVP-positive neurons forming asymmetric
      type of synapses. CONCLUSION: The findings are the first data on the synaptic
      contacts of glutamatergic axon terminals with neurochemically identified neurons
      in the suprachiasmatic nucleus.

PMID- 17451062
TI  - Association of apolipoprotein E polymorphism with age-related macular
      degeneration and Alzheimer's disease in south-western Hungary.
AB  - BACKGROUND: Age-related macular degeneration (AMD) and Alzheimer dementia (AD)
      show similarities (advanced age, formation of deposits of similar content).
      Recently apolipoprotein E 2 (apoE 2) has been associated with AMD, while apoE4
      with AD. The question of coexistence, especially with respect to the genetic
      background has not been studied earlier. We investigated, therefore, the
      occurrence of AMD in AD patients and compared their lipid profile and apoE
      polymorphism. METHODS: - 49 AMD, 32 AD and 27 control patients were examined
      (risk factors, visual acuity, slit lamp biomicroscopy, fundoscopy). Following
      measurement of triglyceride, total and HDL cholesterol levels, apoE mutation
      analysis was performed. RESULTS: AMD was found in 8% of the cooperating AD
      patients. The prevalence of the apoE 4 isoforms in the AMD, AD and the control
      patients was 2%, 47% and 22%, while that of apoE 2 was 17%, 6% and 7%,
      respectively. The prevalence of apoE 3 isoform was 82%, 41% and 71%,
      respectively. Triglyceride, total and HDL cholesterol were in the reference
      range; however, AD patients were characterized by a lower total cholesterol
      value. CONCLUSION: The new finding of this publication is the rare occurrence of
      AMD among AD patients. The higher frequency of apoE 4 among the AD population,
      and the higher frequency of apoE 2 among AMD patients in the South-Western region
      of Hungary confirms the findings of other investigators.

PMID- 17451063
TI  - Histochemistry of the extracellular matrix in the snail central nervous system.
AB  - Even tough the central nervous system (CNS) of gastropods has long been used as a
      model for studying different neuronal networks underlying behaviors, there is
      only little information on the molecular components of the extracellular matrix
      (ECM) of the nervous tissue. Therefore, the aim of the present study was to
      identify some of the ECM molecules by acid-base histochemistry. Staining with
      alcian blue at strong acidic pH, and with acridine orange at different pH and
      salt concentrations was carried out on cryostat sections taken from CNS
      preparations of adult specimens of the terrestrial snail, Helix pomatia, and the
      aquatic species, Lymnaea stagnolis, in order to visualize mild (carboxyl) and
      strong (sulphate) acidic groups, which are characteristic for different
      glucosaminoglycans. According to our findings, sulphated proteoglycans were
      abundant in the periganglionic sheath of both species, and they also occurred in
      the neuropil of Helix, whereas they were absent in Lymnaea. The interperikaryonal
      space contained mainly carboxyl residues, which might refer to the presence of
      hyaluronic acid. It is concluded that the ECM of the snail CNS, similarly to that
      in vertebrates, is partly composed of polymer macromolecules of different
      chemical properties. It is suggested that adaptation to environmental conditions
      and/or altered neuronal plasticity are responsible for the differences found in
      chemical characters of the ECM molecules between the two snail species.

PMID- 17451064
TI  - Effect of local (intracerebral and intracerebroventricular) administration of
      tyrosine hydroxylase inhibitor on the neuroendocrine dopaminergic neurons and
      prolactin release.
AB  - BACKGROUND AND PURPOSE: Hypothalamic dopamine (DA), the physiological regulator
      of pituitary prolactin (PRL) secretion, is synthesized in the neuroendocrine
      dopaminergic neurons that projects to the median eminence and the
      neurointermediate lobe of the pituitary gland. The rate-limiting step of DA
      biosynthesis is catalyzed by the phosphorylated, therefore activated, tyrosine
      hydroxylase (TH) that produces L-3,4-dihydroxy-phenylalanine from tyrosine. The
      aims of our present study were to investigate 1. the effect of local inhibition
      of the DA biosynthesis in the hypothalamic arcuate nucleus on PRL release, and to
      get 2. some information whether the phosphorylated TH is the target of enzyme
      inhibition or not. METHODS: A TH inhibitor, alpha-methyl-p-tyrosine was injected
      either intracerebro-ventricularly or into the arcuate nucleus of freely moving
      rats and plasma PRL concentration was measured. Immunohistochemistry, using
      antibodies raised against to native as well as phosphorylated TH were used to
      compare their distributions in the arcuate nucleus-median eminence region.
      RESULTS: Intracerebro-ventricular administration of alpha-methyl-p-tyrosine has
      no effect, unlike the intra-arcuatus injection of enzyme inhibitor resulted in a
      slight but significant elevation in plasma PRL. Parallel with this, the level of
      DA and DOPAC were reduced in the neurointermediate lobe while no change in
      norepinephrine concentration can be detected indicating a reduced biosynthesis of
      dopamine following TH inhibition. On the other hand, systematic application of
      the alpha-methyl-p-tyrosine that inhibits TH activity located in DA terminals of
      the median eminence and the neurointermediate lobe, resulted in the most
      significant elevation of PRL. CONCLUSION: Our results suggest that alpha-methyl-p
      tyrosine administered close to the neuroendocrine dopaminergic neurons was able
      to inhibit only a small proportion of the TH. Moreover, it also indicate that the
      majority of the activated TH can be found in the axon terminals of dopaminergic
      neurons, therefore, the DA released into the pituitary portal circulation is
      synthesized at this site.

PMID- 17451065
TI  - Glutamatergic phenotype of hypothalamic neurosecretory systems: a novel aspect of
      central neuroendocrine regulation.
AB  - While three decades ago, the co-existence of classical neurotransmitters and
      peptide neuromodulators in a single neuronal cell was considered to be rather
      exceptional, the phenomenon that neurons have a complex transmitter phenotype now
      appears to be the general rule. Parvicellular and magnocellular neurosecretory
      systems consist of neuronal cells which are specialized in secreting peptide
      neurohormones into the blood-stream to regulate hypophyseal functions. This mini
      review, dedicated to the memory of Mariann Fodor, summarizes the current
      knowledge about the classical neurotransmitter content of different hypothalamic
      neurosecretory systems, with a special focus on the occurrence and putative
      functions of glutamate in parvicellular and magnocellular neurosecretory cells.

PMID- 17451066
TI  - Molecular architecture of the cannabinoid signaling system in the core of the
      nucleus accumbens.
AB  - Several abused drugs are known to alter glutamatergic signaling in reward
      pathways of the brain, and these plastic changes may contribute to the
      establishment of addiction-related behaviour. Glutamatergic synapses of the
      prefrontal cortical projections to the nucleus accumbens (nAcb)--which are
      suggested to be under endocannabinoid (eCB) control - play a central role in the
      addiction process. The most abundant eCB in the brain is 2-arachi-donoyl-glycerol
      (2-AG). It is synthesized by diacylglycerol lipase alpha (DGL-alpha), and exerts
      its action via type 1 cannabinoid receptors (CB1). However, the precise
      localization of DGL-alpha and CB1 - i.e. the sites of synthesis and action of 2AG
      - is still unknown. At the light microscopic level, immunocytochemistry revealed
      a granular pattern of DGL-alpha distribution in the core of the nAcb. Electron
      microscopic analysis confirmed that these granules corresponded to the heads of
      dendritic spines. On the other hand, presynaptic axon terminals forming
      excitatory synapses on these spineheads were found to express CB1 receptors. Our
      results demonstrate that the molecular constituents for a retrograde
      endocannabinoid control of glutamatergic transmission are available in the core
      of the nAcb, and their relative subcellular location is consistent with a role of
      2-AG in addiction-related plasticity of cortical excitatory synapses in this
      reward area.

PMID- 17451067
TI  - Immobilization induced fos expression in the medial and lateral hypothalamic
      areas: a limited response of hypocretin neurons.
AB  - Induction of Fos, a proto-oncogene c-fos protein product, was
      immunohistochemically examined in the rat hypothalamic neurons 3 h after a single
      (1 x120 min) or repeated (7x 120 min) immobilization (IMO) stress. The aim of the
      present study was to reveal a possible parallelism in the cell activation between
      the medial and lateral hypothalamic neurons, especially between the stress
      responsive neurons in the hypothalamic paraventricular nucleus (PVN) and
      hypocretin (Hcrt) synthesizing neurons, i.e. suspected stress active neurons of
      the lateral hypothalamus. After IMO, the animals were perfused and their brains
      processed with immunohistochemistry for Fos or Fos/Hcrt proteins. Acute IMO
      elicited extensive Fos expression in both the examined areas. Excessive Fos
      expression was mainly seen in the PVN, while Hcrt neurons failed to show a broad
      response (appr. 5%) to single IMO. Clear occurrence of Fos signal was also seen
      in both hypothalamic areas of IMO-habituated rats. However, in these animals, in
      both areas examined, the number of Fos neurons was considerably suppressed,
      including the PVN. These results indicate that IMO is able to evoke a concurrent
      activation of Fos in many medial and lateral hypothalamic neurons. However, the
      scanty response of Hcrt neurons to acute IMO does not allow to assort them to a
      distinct IMO stress-responsive neuronal phenotypes of the brain.

PMID- 17451068
TI  - The role of vasopressin in chronic stress studied in a chronic mild stress model
      of depression.
AB  - BACKGROUND AND PURPOSE: Vasopressin plays an important role in the hypothalamo
      pituitary-adrenal axis regulation as well as in stress-related disorders. A
      common view suggested that the role of vasopressin is especially important during
      chronic stresses. Here we tested the hypothesis that vasopressin-deficient rats
      may be more resistant to the development of chronic hypothalamo-pituitary-adrenal
      axis hyperactivity after chronic mild stress. METHODS: Male vasopressin deficient
      Brattleboro rats were compared to their heterozygous litter mates. Chronic mild
      stress consisted of different mild stimuli (e.g. wet cages, restraint) for 6
      week. The corticosterone changes were followed by repeated tail cutting and
      organs and blood were collected from decapitated rats. RESULTS: In controls,
      chronic mild stress resulted in symptoms of chronic stress state characterized by
      typical somatic (body weight reduction, thymus involution) and endocrine changes
      (resting plasma ACTH and corticosterone elevation and POMC mRNA elevation in
      anterior lobe of the pituitary). Unexpectedly, the lack of vasopressin could not
      influence any chronic mild stress-induced changes. CONCLUSION: Somatic changes
      and endocrine effects of chronic mild stress are similar in control and
      vasopressin deficient animals. This suggests that either vasopressin is not
      indispensable for activating the hypothalamo-pituitary-adrenal axis by chronic
      stress or the absence of vasopressin is compensated by other mediators (e.g. CRH)
      in Brattleboro rats.

PMID- 17451069
TI  - Characterization of specific succinate binding site in brain synaptic membranes.
AB  - A synaptic receptor for gamma-hydroxybutyric acid (GHB) --a naturally occurring
      metabolite of succinic acid--interacting succinate has been disclosed in rat and
      human nucleus accumbens (NA) subcellular fractions, but the molecular properties
      of this recognition site were not characterised. To address the presumed
      recognition site for succinate, the pharmacological profile of [3H]succinate
      binding to synaptic membranes prepared from rat forebrain and human NA samples
      has been investigated. Specific [3H]succinate binding sites in the human NA
      synaptic membrane fraction showed a strong pH-dependence and were characterized
      by binding of succinate (IC50 succinate=2.9+/-0.6 microM), GHB (IC50 GHB=2.1 +/
      1.3 microM) and gap junction blocker carbenoxolone (IC50 = 7.1 +/-5.8 microM). A
      similar [3H]succinate binding profile was found in rat forebrain synaptic
      membrane fractions. We conclude the existence of a pHo-dependent synaptic
      membrane binding site for the intermediary metabolite succinate. The
      pharmacological properties of this recognition site may possibly suggest the
      existence of a hemichannel-like target protein for succinate.

PMID- 17451070
TI  - Comparative neurochemical study of the thoracic and sacral intermediolateral
      nuclei in the rat.
AB  - BACKGROUND AND PURPOSE: In view of the known functional differences, the
      neurochemical character of the thoracic and sacral intermediolateral nuclei were
      compared. METHODS: Neurons and the afferent fiber components were labeled using
      antibodies raised against neurofilament, neural nuclear protein,
      cholinacetyltransferase, nitric oxide synthase, neurokinin receptor-1, substance
      P, calcitonin gene-related peptide, micro-opiate receptor-1 and vesicular
      glutamate transporter type 1 in rats. Biontinylated isolectin IB4 was used to
      label unmyelinated primary afferent fibers. Specimens were analyzed with confocal
      laser microscope. RESULTS AND CONCLUSIONS: The thoracic and sacral
      intermediolateral nuclei are similar in the chemical character of the neurons. In
      the thoracic segments the dendrites of the labeled neurons followed a transverse
      path towards the neurons located at both sides of the midline above the central
      canal. The transverse orientation of the dendrites in the sacral segment was less
      evident. Calcitonin gene-related peptide, isolectin IB4 and micro-opiate receptor
      1 immunopositive afferent fibers arborize only in the sacral intermediolateral
      nucleus. We conclude that fine caliber primary afferent fibers, departing from
      the adjacent superficial dorsal horn, terminate in the sacral intermediolateral
      nucleus. It is probable that the preganglionic parasympathetic neurons in the
      nucleus receive synapses from the primary afferent fibers.

PMID- 17451071
TI  - Avoiding antibacterial overuse in primary care.
AB  - Reducing excessive and inappropriate use of antibacterials is key to tackling the
      global problem of increasing prevalence of resistant organisms. Here we consider
      which strategies in primary care can help healthcare professionals and their
      patients to achieve this objective.

PMID- 17451072
TI  - Is there a place for duloxetine?
AB  - Duloxetine, a combined serotonin and norepinephrine reuptake inhibitor, is
      licensed in the UK under two brand names for a total of three different
      indications. It is available as Cymbalta (jointly promoted by Boehringer
      Ingelheim and Lilly) for the treatment of patients with major depression, or with
      diabetic peripheral neuropathic pain; and as Yentreve (Lilly) for the treatment
      of women with "moderate to severe" stress urinary incontinence. Here we consider
      whether duloxetine has a role in the treatment of patients with any of these
      conditions.

PMID- 17451073
TI  - Continued catch-up growth in neonatal endocrinology.

PMID- 17451074
TI  - The diagnosis of children with central diabetes insipidus.
AB  - Central diabetes insipidus is the end result of a number of different diseases
      that affect the hypothalamic-neurohypophyseal system. In many patients,
      especially children and young adults, it is caused by the destruction or
      degeneration of neurons that originate in the supraoptic and paraventricular
      nuclei of the hypothalamus. The known causes of these lesions include germinoma
      or craniopharyngioma; Langerhans cell histiocytosis; local inflammatory,
      autoimmune or vascular diseases; trauma resulting from surgery or an accident;
      sarcoidosis; metastases; and midline cerebral and cranial malformations. In rare
      cases, genetic defects in AVP synthesis that are inherited as autosomal dominant,
      autosomal recessive or X-linked recessive traits are the underlying cause.
      Accurate diagnostic differentiation is essential for both safe and effective
      disease management. Proper etiological diagnosis can be achieved via a series of
      steps that start with clinical observations and then progress, as needed, to more
      sophisticated methods. Indeed, magnetic resonance imaging (MRI) represents the
      examination method of choice for evaluating hypothalamic-pituitary-related
      endocrine diseases due to its ability to provide strongly-contrasted high
      resolution multi-planar and spatial images. Specifically, MRI allows a detailed
      and precise anatomical study of the pituitary gland by differentiating between
      the anterior and posterior pituitary lobes. MRI identification of pituitary
      hyperintensity in the posterior part of the sella, now considered to be a clear
      marker of neurohypophyseal functional integrity, together with careful analysis
      of pituitary stalk shape and size, have provided the most striking recent
      findings contributing to the diagnosis and understanding of some forms of
      'idiopathic' central diabetes insipidus.

PMID- 17451075
TI  - Hypothalamic hamartoma, gelastic epilepsy and precocious puberty.

PMID- 17451076
TI  - Catch-up growth in infants born small for gestational age--a longitudinal study.
AB  - BACKGROUND: Epidemiological studies correlate low birth weight and the subsequent
      development of diabetes mellitus (DM). Early changes in insulin resistance in
      infants with catch-up growth (CUG) have not been evaluated in our population.
      AIM: To identify dietary and metabolic features associated with CUG in infants
      born small for gestational age (SGA) at 1 year old. METHODS: In a cohort study of
      88 term infants (44 SGA and 44 appropriate for gestational age [AGA]),
      breastfeeding and weaning age were registered. Anthropometric measurements,
      glucose, insulin, and leptin concentrations were measured at birth and at 1 year
      old. RESULTS: A history of DM in a second-degree relative (p = 0.01) and
      complementary breastfeeding (p = 0.0003) were higher in SGA compared to AGA
      infants. Ten (13.6%) infants showed CUG in length and weight combined. They had
      lower weight, glucose, IR index, and leptin concentrations at birth than those
      without CUG. After logistic regression analysis for factors related to weight
      CUG, gender, weaning age, birth weight and leptin concentration at birth were
      included in the model (R2 = 0.31; p = 0.00004). CONCLUSIONS: Female gender, early
      weaning, lower birth weight, and lower leptin concentration at birth are related
      to weight CUG in Mexican infants.

PMID- 17451077
TI  - Inflammatory and growth mediators in growing preterm infants.
AB  - Little is understood about the optimal balance between IGF-I and antagonistic
      inflammatory mediators, such as IL-6, in growing preterm infants. Using a
      prospective cohort study, we investigated the relationship between postnatal
      growth of preterm infants and key growth and inflammatory mediators. We studied
      51 stable, growing preterm infants (mean gestational age: 27.8 +/- 0.4 weeks,
      mean birth weight: 1,032.8 +/- 50.6 g). IL-6 and IL-1ra (reflecting stress/
      inflammation) and IGF-I and GHBP (reflecting anabolic activity and GH
      sensitivity) were measured at enrollment and discharge using ELISA. During the
      observation period (mean 6.1 +/- 0.34 weeks) there was a significant increase in
      weight (1,396 +/- 81 g, p < 0.0001). IGF-I increased from 46.6 +/- 4.1 to 88.7 +/
      5.2 ng/ml (p < 0.001). In contrast, IL-6 decreased from 9.5 +/- 1.0 to 2.3 +/-
      0.34 pg/ml (p <0.001) and IL-1ra from 6,042 +/- 362 to 4,851 +/- 365 ng/ml (p =
      0.007). GHBP increased from 65.8 +/- 6.7 to 82.5 +/- 7.9 ng/ml (p = 0.003). IL-6
      was inversely correlated with IGF-I (p < 0.001). In addition, a multiple
      regression model showed IGF-I levels correlated positively and IL-6 levels
      inversely with various parameters of growth. Growth in preterm infants is
      characterized by increases in IGF-I and GHBP with simultaneous decreases in IL-6
      and IL-1ra. Efforts to optimally balance inflammatory and growth mediators may
      benefit somatic growth in infants very early in life.

PMID- 17451078
TI  - Ovarian volume and uterine length in neonatal girls.
AB  - This study was undertaken to establish reference values for the size of the
      uterus and ovaries in newborns. We also studied the frequency and follow-up of
      functional ovarian cysts in healthy neonatal girls. Pelvic ultrasonography was
      performed on 55 normal newborns. Right and left ovarian volumes positively
      correlated with birth weight and length, but there was no correlation between
      uterine length and any of the parameters studied. In a total of 55 newborns, 16
      ovarian cysts were detected by transabdominal ultrasound: six neonates (10.9%)
      had cysts on the left side, ten (18.2%) on the right side, and two (3.6%) had
      bilateral cysts. All were uncomplicated homogeneous cysts and resolved
      spontaneously. A higher percentage of cysts was found in the 26 infants weighing
      2,500-2,999 g, ten (38.4%) of whom had cysts, than in the 29 infants weighing
      3,000 g or more, four (13.7%) of whom had cysts (p < 0.05). Newborns with cysts
      were followed up, and the cysts resolved spontaneously within 3 months in all but
      three patients in whom resolution took almost 6 months. Right and left ovarian
      volumes were positively correlated with birth weight and length, but no
      significant correlation was found between uterine length and any parameter. In
      conclusion, ovarian volume was found to be reduced in newborns with relatively
      low birth weight as well as intra-uterine growth retardation. Functional cysts
      were more prevalent among low birth weight girls. We suggest that small ovaries
      and ovarian dysfunction may have a prenatal origin, and further studies on normal
      and growth-retarded newborns are needed.

PMID- 17451079
TI  - Gonadal function in low birth weight infants: a pilot study.
AB  - OBJECTIVE: To evaluate gonadal function and anti-Mullerian hormone (AMH) serum
      concentrations during the first 3 months of life in low birth weight (low-BW) and
      normal birth weight (normal-BW) infants. INFANTS: Twenty low-BW and 29 normal-BW
      infants were studied. METHODS: The pituitary-gonadal axis was evaluated by a GnRH
      agonist test (leuprolide acetate, 10 microg/kg s.c.). Circulating concentrations
      of gonadotropins, steroid hormones, sex hormone binding globulin, inhibin B and
      AMH were determined by specific assays. RESULTS: In both sexes, basal
      concentrations of gonadotropins, sex steroids, sex hormone binding globulin and
      inhibin B were similar between low-BW and normal-BW infants. However, AMH
      concentrations were significantly higher in low-BW compared to normal-BW females
      (p = 0.004). This was not observed in males. After leuprolide administration,
      estradiol concentrations were higher in low-BW compared to normal-BW females (p =
      0.043). In males, post-stimulated sex steroid concentrations were similar in both
      groups except for 17-OHP, which was significantly higher after leuprolide in the
      low-BW group (p = 0.023). CONCLUSIONS: An increase in AMH and post-stimulated
      estradiol serum concentrations suggests altered follicular development in low-BW
      girls. In contrast, the normal circulating levels of AMH and inhibin B seem to
      indicate that Sertoli cell function is normal in low-BW boys. We suggest that
      ovarian function seems to be more vulnerable than testicular function in infants
      with intrauterine growth restriction.

PMID- 17451080
TI  - Longitudinal measurements of bone status in preterm infants.
AB  - BACKGROUND: Quantitative ultrasound measurement of the speed of sound (SOS)
      through bone has been investigated as a means of assessing bone status in preterm
      infants. Few studies report longitudinal measurements. OBJECTIVE: To assess
      longitudinal changes in bone SOS in preterm infants. METHODS: Sixty preterm
      infants with gestational ages of < 33 weeks and with birth weight appropriate for
      gestational age (AGA), and 48 healthy, term AGA infants were enrolled. SOS
      measurements of the tibia were made within the first week of life in the preterm
      infants, and within the first 72 hours of life in the term infants. During their
      hospital stay, weekly measurements of tibial SOS were made in 29 of the preterm
      infants, who were divided into three gestational age groups: Group 1: 24-26 weeks
      (n = 8), Group 2: 27-29 weeks (n = 9), and Group 3: 30-32 weeks (n = 12).
      RESULTS: The median SOS value for the 60 newborn preterm infants was
      significantly lower than that for the 48 newborn term infants (2,924 versus 3,036
      m/sec, p < 0.001). At each time point, SOS values for each of the preterm infant
      gestational age groups were significantly lower than the term newborn infant SOS
      values. SOS values decreased significantly over time for the entire cohort of 29
      preterm infants (p < 0.001), and for Groups 1 (p = 0.015) and 2 (p = 0.003). At
      several time points, there was a significant negative correlation between serum
      alkaline phosphatase levels and SOS values, and a significant positive
      correlation between serum phosphorus levels and SOS values. CONCLUSION: SOS
      measurements of the tibia decline during hospitalization in preterm infants,
      suggesting a progressive loss of bone strength. Longitudinal measurements of bone
      SOS in combination with serum alkaline phosphatase and serum phosphorus levels
      may identify infants at risk of developing osteopenia of prematurity.

PMID- 17451081
TI  - Hereditary vitamin D-resistant rickets in Greek children: genotype, phenotype,
      and long-term response to treatment.
AB  - We describe four patients (two pairs of children from two unrelated kindreds)
      from a Greek island, suffering from hereditary vitamin D-resistant rickets
      (HVDRR) with alopecia. There were two different homozygous mutations in the
      vitamin D receptor (VDR) gene of the affected members of the two kindreds that
      resulted in a truncated or missing receptor. The disorder began in early infancy
      with similar clinical, biochemical and radiological findings in all four
      patients, namely, alopecia (which provided the initial diagnostic evidence for
      HVDRR), rachitic deformities, hypocalcemia, hypophosphatemia, secondary
      hyperparathyroidism, and elevated serum levels of 1,25-dihydroxyvitamin D;
      however, the patients of kindred B had a more severe clinical expression.
      Treatment options include oral or intravenous calcium and active vitamin D
      metabolites. The response varies widely in different cases. Our patients were
      initially treated with high doses of 1alpha(OH)D3 and oral calcium
      supplementation. Kindred A patients had a satisfactory response to this regimen,
      while kindred B patients presented clinical and biochemical improvement when
      1alpha(OH)D3 was changed to 1,25(OH)2D3. In the older patients of each kindred,
      treatment requirements gradually decreased during puberty, and therapy was
      finally discontinued before adulthood.

PMID- 17451082
TI  - Insulin resistance and metabolic syndrome in children of parents with diabetes
      mellitus.
AB  - The aim of this prospective study was to research features of insulin resistance
      and metabolic syndrome in offspring of diabetic parents and to find out whether
      there is a risk of developing type 2 diabetes mellitus (DM) in these children.
      Study participants were 30 children of parents with type 1 DM (DM1) (Group I) and
      11 children of parents with type 2 DM (DM2) (Group II) who were being followed up
      in the Diabetes Department of Haseki Research and Training Hospital. The results
      were compared with a control group of 17 children in the same age group (Group
      III). There were no statistically significant differences between the Group I and
      the control group in fasting blood glucose, oral glucose tolerance test values,
      1st 2nd and hour insulin, homeostasis model assessment (HOMA) values, body mass
      index (BMI), systolic and diastolic blood pressure, and lipid parameters, i.e.
      HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, total cholesterol, and
      triglycerides. Fasting, 1st and 2nd hour blood insulin levels, HOMA values, BMI,
      and systolic blood pressure values were significantly higher in Group II compared
      to the control group (p < 0.05). There were no statistically significant
      differences between Group II and the control group in lipid parameters, fasting
      blood glucose, OGTT values, or diastolic blood pressure. We conclude that in our
      population there is a tendency of insulin resistance and metabolic syndrome in
      the offspring of parents with DM2, and a risk for developing DM2. Thus, children
      of patients with DM2 should be followed up so as to recognize early metabolic
      defects of glucose metabolism and to plan effective preventive efforts to reduce
      cardiovascular and atherosclerotic risk factors.

PMID- 17451083
TI  - Congenital hyperinsulinism in an infant caused by a macroscopic insulin-producing
      lesion.
AB  - Congenital hyperinsulinism is the most common cause of persistent neonatal
      hypoglycemia. Severe congenital hyperinsulinism is most often due to inactivating
      mutations in either the ABCC8 or KCNJ11 genes, which encode the SUR1 and Kir6.2
      proteins, respectively--the two components of the ATP-sensitive K+ (KATP)
      channel; neonatal hypoglycemia due to macroscopic insulin-producing pancreatic
      lesions or adenomas are extremely rare. KATP channel hyperinsulinism is
      classified as diffuse or focal, the latter being associated with paternally
      derived mutations of ABCC8 or KCNJ11 and somatic loss of heterozygosity of the
      maternal alleles. KATP channelopathies usually produce microscopic intra
      pancreatic lesions and are typically unresponsive to drug therapy, requiring >
      95% pancreatectomy for diffuse disease and occasionally more limited pancreatic
      resection for focal disease; macroscopic pancreatic lesions and adenomas are
      focally excised. We describe a 1 month-old infant with severe congenital
      hyperinsulinism who had a macroscopic insulin-producing pancreatic lesion
      successfully treated with focal lesion enucleation.

PMID- 17451084
TI  - Adrenal haemorrhage with cholestasis and adrenal crisis in a newborn of a
      diabetic mother.
AB  - The large hyperaemic foetal adrenal gland is vulnerable to vascular damage. This
      may occur in the neonatal period as a consequence of difficult labour, or its
      aetiology may not be apparent. The spectrum of presentation is considerable,
      ranging from asymptomatic to severe life-threatening intra-abdominal haemorrhage.
      The presentation of adrenal insufficiency may be delayed but the regenerative
      capacity of the adrenal is great, and most adrenal haemorrhage is not associated
      with significantly impaired function. Some reports showed that cholestatic
      hepatopathy with congenital hypopituitarism reversed by hydrocortisone treatment
      is considered in the context of the endocrine syndrome, probably as a consequence
      of the adrenal failure. We describe a case of bilateral adrenal haemorrhage with
      hepatitis syndrome and persistent hypoglycaemia in a newborn male with striking
      features of neonatal cholestasis and adrenal crisis.

PMID- 17451085
TI  - Tamoxifen treatment in a patient with blepharophimosis-ptosis-epicanthus inversus
      syndrome and peripheral precocious puberty.
AB  - Patients with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) can be
      classified as types 1 or 2, according to the presence or not of ovarian failure.
      We report a 5 year-old girl with BPES and large multicystic ovaries who developed
      peripheral precocious puberty with thelarche (Tanner stage III) and pubarche
      (Tanner stage II). Pelvic ultrasound revealed pubertal uterus and enlarged
      multicystic ovaries. Fibrous dysplasia and McCune-Albright syndrome were ruled
      out. Treatment with an estrogen antagonist was started (tamoxifen, 10 mg/day),
      achieving regression of thelarche. Tamoxifen treatment was stopped at 10-(7/12)
      years, and growth velocity and skeletal maturation rate returned to normal. No
      treatment-associated adverse effects were observed.

PMID- 17451086
TI  - Right testicular necrosis and left vanishing testis in a neonate.
AB  - We describe a rare case of right testicular necrosis and left vanishing testis in
      a neonate. The patient presented with a right swollen testis and left non
      palpable testis at birth. Exploratory laparotomy was performed at 23 days after
      birth, and the right testis was extirpated because of extensive necrosis due to
      torsion of the spermatic cord. Histopathological examination revealed a massively
      necrotic testicular structure with hypertrophy of Leydig cells.
      Hypergonadotropinemia was also recognized before operation. On laparoscopy at the
      age of 5.3 years, a normal left vas deferens and spermatic vessels exiting
      through the internal inguinal ring were confirmed, although the patient's left
      testis was not found in the intraperitoneal cavity. An hCG test demonstrated no
      response of serum testosterone. These findings suggested a diagnosis of left
      vanishing testis due to testicular regression. We therefore speculated that
      bilateral asynchronous testicular torsion had occurred prenatally in this
      patient.

PMID- 17451087
TI  - A clinical prediction model for the presence of peripheral arterial disease--the
      benefit of screening individuals before initiation of measurement of the ankle
      brachial index: an observational study.
AB  - Measurement of the ankle-brachial index (ABI) can provide important information
      about the presence of subclinical atherosclerosis. Performing the ABI in the
      overall population is not feasible, but it can be used in a selected population.
      A simple prediction rule could be of much use to estimate the risk of an abnormal
      ABI. This was designed as an observational study in the setting of 955 general
      practices in The Netherlands. A total of 7454 patients aged > or = 55 years
      presenting with at least one vascular risk factor (smoking, hypertension,
      diabetes, and hypercholesterolemia) and no complaints of intermittent
      claudication were included. Patients were selected by the general practitioner
      during visiting hours and from medical records. Main outcome measures included
      the prevalence of PAD, defined as an ABI below 0.9, which was related to vascular
      risk factors using regression analyses on which the PREVALENT clinical prediction
      model was developed. The overall prevalence of PAD was 18.4%. Since the treatment
      of individuals with a history of coronary heart disease and cerebrovascular
      disease will not be influenced by the finding of asymptomatic PAD, these
      individuals were not taken into account for the development of the clinical
      prediction model. Analyses showed a significantly increased risk for PAD with
      increasing age, smoking, and hypertension. The clinical prediction model giving
      risk factor points per factor (age: 1 point per 5 years starting at 55 years;
      ever smoked: 2 points; currently smoking: 7 points; and hypertension: 3 points),
      showed a proportional increase of the PAD prevalence with each increasing risk
      profile (range: 7.0-40.6%). In conclusion, based on the PREVALENT clinical
      prediction model, the general practitioner is able to identify a high-risk
      population in which measurement of ABI is useful.

PMID- 17451088
TI  - Assessment of peripheral vascular endothelial function in the ambulatory setting.
AB  - Until now, peripheral vascular endothelial function testing has been performed in
      research laboratories under highly controlled conditions, thus limiting its
      clinical applicability. In this study, we evaluated endothelial function in two
      peripheral vascular beds before and during reactive hyperemia in an outpatient
      clinic setting. The brachial artery was imaged with a portable ultrasound device
      and changes in vessel diameter were expressed as percent flow-mediated dilation
      (%FMD). Pulse wave amplitude of the finger was detected by peripheral arterial
      tonometry (PAT) and PAT hyperemia was defined as the maximal plethysmographic
      recording compared to baseline. Sixty individuals (43 men) were enrolled with an
      average age 53 +/- 2 years (mean +/- SE). The 31 individuals with more than two
      cardiac risk factors (CRF) had lower FMD (7.0 +/- 1.1%) and PAT hyperemia (2.1 +/
      0.9) compared to the 29 individuals with 0-2 CRF (FMD 11.3 +/- 0.8%, PAT
      hyperemia 2.4 +/- 0.1; p < 0.05 for both). The 32 individuals with coronary
      artery disease (CAD) had lower FMD (6.8 +/- 1.1%) and PAT hyperemia (2.0 +/- 0.1)
      compared to the 28 individuals without CAD (FMD 11.5 +/- 0.8%, PAT hyperemia 2.4
      +/- 0.1; p < 0.05 for both). Thus, peripheral vascular endothelial function
      testing in the ambulatory setting correlates with the extent of CAD risk and the
      presence or absence of CAD. In conclusion, these data suggest that peripheral
      vascular endothelial function testing is feasible in ambulatory patients, and
      this is an important next step in bringing this technology to clinical
      applicability.

PMID- 17451089
TI  - Prevalence of erectile dysfunction in vascular surgery patients.
AB  - Erectile dysfunction (ED) is frequently associated with cardiovascular disease.
      Epidemiological data on the frequency of ED in vascular surgery patients is
      rarely reported. We evaluated the prevalence of this comorbidity in patients
      consulting the vascular surgery outpatient clinic. Over a 6-month period, a short
      version of the International Index of Erectile Function (IIEF) questionnaire
      consisting of six ED-relevant questions was handed out to 440 vascular surgery
      outpatients. Clinical data were collected from patients' records. Linear
      regression models with forward selection were used to investigate associations
      between erectile function score and possible risk factors. The return rate was
      31% (137 patients). Eight patients (6%) were taking phosphodiesterase inhibitors.
      ED, as defined by an erectile function score of 25 or less and/or use of
      phosphodiesterase inhibitors, was found in 90% (95% CI: 84% to 95%) of cases.
      Moderate or severe ED, as defined by an erectile function score of 16 or less
      and/or use of phosphodiesterase inhibitors, was found in 70% (95% CI: 62% to 78%)
      of cases. Increased age, abdominal aortic aneurysm, peripheral arterial disease,
      urologic disease, insulin-dependent diabetes mellitus, and use of beta-blockers
      were significantly associated with a lower erectile function score. In
      conclusion, erectile dysfunction is a frequent and often missed comorbidity in
      vascular surgery patients. While ED may have a profound impact on the patient's
      quality of life, attention should also be paid to the patient's preoperative
      sexual function, considering the availability of oral pharmacotherapies and
      possible consequences concerning liability in postoperative patients in whom pre
      existing ED was not identified properly.

PMID- 17451090
TI  - Angiotensin II promotes the inflammatory response to CD40 ligation via TRAF-2.
AB  - A plethora of evidence supports a link between inflammation and atherogenesis.
      Both the vasoactive peptide angiotensin II (ANG II) as well as the CD40/CD154
      signaling pathway exhibit proinflammatory properties with a direct influence on
      atherogenesis. We therefore tested the hypothesis that ANG II interacts with
      CD40/CD154 in human vascular smooth muscle cells (SMC). ANG II did not increase
      expression of CD40 in human SMC. However, when SMC were prestimulated with ANG II
      and thereafter stimulated with CD154, the ligand for CD40, the release of IL-6 as
      a marker of inflammatory activation was augmented compared to cells not primed
      with ANG II. TNF receptor-associated factor 2 (TRAF-2), an important adaptor
      protein involved in CD40 signaling, but not TRAF-5 or -6, was increased by ANG II
      via activation of the angiotensin II type 1 (AT1) receptor subtype. These results
      suggest that a signaling pathway downstream of CD40 may be altered by ANG II
      prestimulation. Thus, ANG II can also indirectly cause inflammatory activation of
      vascular SMC. The data show a novel link between the proatherogenic vasoactive
      peptide ANG II and cell-cell contact-mediated inflammatory pathways and implicate
      options for the prevention and therapy of atherosclerotic disease.

PMID- 17451091
TI  - Purple glove syndrome following intravenous phenytoin administration.
AB  - Purple glove syndrome (PGS) is a rare complication of intravenous phenytoin use
      that typically presents with pain, edema, and discoloration at the injection site
      that spreads to the distal limb. Several risk factors have been associated with
      the development of PGS; however, the etiology remains unknown. We present a case
      of PGS and briefly review the current understanding of this syndrome.

PMID- 17451092
TI  - Images in vascular medicine. Persistent abdominal pain from a perforated inferior
      vena cava filter.

PMID- 17451093
TI  - ACCF/SCAI/SVMB/SIR/ASITN 2007 Clinical Expert Consensus Document on carotid
      stenting.

PMID- 17451094
TI  - [Filosofical legacy of Julian Marias].
AB  - Julian Marias was a philosopher, a prolific writer member of the Royal Academy of
      the Spanish Language, Prince of Asturias award in 1996. Marias thought could only
      be explained in the context of his life and his long term relation to Ortega y
      Gasset, both co-founded the Instituto de Humanidades. Between the late 1940s and
      the 1970s Marias taught at numerous institutions in the United States. Marias
      wrote on a wide variety of subjects during his long career, his History of
      Philosophy is widely regarded as the greatest work in the Spanish language on the
      history of philosphy.

PMID- 17451095
TI  - [Historical evolution of prosthetic heart valves].
AB  - The historical evolution of the prosthetic heart valves is resumed, quoting the
      first experimental steps, the conditions that a prosthesis has to fulfil, and the
      first clinical attempts with the Hufnagel's valve in the treatment of the aortic
      insufficiency (September 11, 1952) and with the Chesterman's in the pathology of
      the mitral valve (July 22, 1955) till the Starr Edwards' ball valve (Agoust 12,
      1960). The characteristics of the different types of ball valve are described
      (Harken, Smeloff, etc), disc valves (Kay-Shiley, Beall, Lillehei-Nakib etc.),
      tilting disc valves (Bjork-Shiley, Hall-Kaster, Omniscience etc), bileaflet
      valves ( St. Jude and others) and biological valves, using autologous tisues
      (diaphragm, fascia lata, pericardium) homologous (aortic and mitral valves,
      duramater) and heterologous (porcine and bovine valves, Carpentier-Edwards,
      Hancock, Ionescu's valve of bovine pericardium), to conclude with the new trends
      with valves made from autologous cells, the valves made with polymers, those
      based on the concept of flexible tubes and finally with those used by
      percutaneous transcatheter implantation (Boudjemline y Bonhoeffer. Cribier.).

PMID- 17451096
TI  - [About creativity].
AB  - The term 'creativity', meaning to produce something out of nothing, is not
      accurate. A definition that included the establishment, the founding or the
      introduction of something anew for the first time would be rather appropiate. The
      most accurate interpretation of the creativity process is the one proposed by
      Alfred Rothenberg which establishes the hypothesis that creativity is due to what
      he calls a 'janusian thinking' characterized by conceiving simultaneously two or
      more opposed ideas, images or concepts. Two examples illustrate such way of
      thinking: one is Einstein's General Theory of Relativity and the other is
      Darwin's Theory of Natural Selection. The overcome of a dualistic thinking while
      keeping full consciousnees, that is, the utilization of both the primary and the
      secondary processes postulated by Freud, would be the key to creative thinking.
      From a neurophysiological point of view, it is very likely that the right
      hemisphere is rather connected to creativity, given that it is a mental state
      that requires non-focalized attention, greater right hemisphere activation, and
      low levels of prefrontal cortical activation allowing cognitive inhibition.

PMID- 17451097
TI  - [Abstract painting, a mental esthetic construction without exact correspondence
      with reality (Jose Guerrero: manuel and corporal expressions in his paintings)].
AB  - It is desirable that a truthful aesthetic experience should be the consequence of
      a complete observation detached from all sorts of commercial, social, political
      or cultural ties. If during this period of admiration of a work of art a personal
      concentration is reached, the admirer perceives a liberation from all sorts of
      limiting ties and a rewarding artistic feeling. A similar type of mental freedom
      must be reached by the artist and prevail during the process of creation which
      must reach its greatest dimension in abstract paintings because not being
      illustrations they demand from the spectator a well developed habit to detect its
      esthetic values, difficult to perceive because they are in the abstract order.
      The dimensions such as perspective, symmetry, lights and shadows, usually
      integrated in figurative paintings to create well defined tridimensional spaces
      are not included in abstractions because this type of geometrical composition is
      not needed. In contemporary abstraction the design itself has lost its formal
      meaning and its protagonist role. It is frequently replaced by abrupt gestures as
      it is the case in the styles named "action painting" (Jackson Pollack) or
      "abstract expressionism" (Antonio Saura). Other abstract painters close to
      "minimalism" simply drop the colors on the canvas without any attempt to design
      but full of aesthetic energy and even single colors uniformly bathe the surface
      of the linen (Rothko). Other american artists of the sixties (Monis Louis) are
      also to be admired. They allow that the deposited and sliding colors themselves
      initiate and finish interesting artistic compositions. They become esential
      creative agents in the painting without being forced to be figurative nor to
      follow the creative will of the artist who, is simply acting as the first
      observer and only intervenes "a posteriori" accepting or rejecting the results.
      Only the colors and under the single influence of their sliding density create
      the shapes and artistic ensembles where there are still perceived their slow
      original movements. The observers of these abstract styles must initiate a
      process of perception without specific norms and wait until the engaging game of
      the colors generate emotional rewards in their minds such as amazement or
      interest that invite them to continue their tuning with the painting. If these
      artistic attraction is not evoked, the observer must be sadly satisfied with a
      simple ocular vision of the painting and again wait until the mental perception
      participates and the aesthetic reward is completed. What the "eyes of the mind"
      see is not a copy of the painting. A mental copy would not include the artistic
      meaning that the work of art contains which only emerges during the mental
      aesthetic encounter between the painting and the observer.

PMID- 17451098
TI  - [Surgical treatment of the aortic root dilatation].
AB  - The aorta is considered as pathologically dilatated when the diameter of the
      aortic root and of the ascending aorta is exceeding 50% of its standard diameter
      for a determined body masc. The aortic root dilatation is frequently associated
      with valve's pathology, rupture and dissection are two serious events that might
      occur; are linked with high mortality and are closely connected to aortic
      diameter and to wall's pathology, so that the elective indication is essential
      and it basically depends on those two factors. There are different technical
      alternatives, anatomical and functional, of the aortic root, the procedure's
      election is most specially based on patient's age, on pathological substract, on
      anticoagulation risk, and on possible infection, etc. We wish to report our
      experience performed from 1990 onto 2004 with 364 cases of aortic root surgery,
      of which 312 were elective interventions and 52 were emergencies, with a
      mortality of 4.8% and 19.2% respectively, and a global mortality of 6.8% using
      the different procedures. The choice of procedure is a multifactorial decision
      and it is necessary try offering the patient, the most idoneus individualized
      solution, according to personal characteristics. The different surgical
      techniques (valved conduits, remodelling procedures, biological grafts, etc.) can
      be carried out with low figures of morbid-mortality and excellent long term
      outcomes.

PMID- 17451099
TI  - [Molecular mechanisms of aging and its prevention by hormonal treatment in rats].
AB  - In two previous communications to the RANM four and two years ago, some data were
      shown supporting the role of GH, Melatonin and Estrogens in the prevention of
      aging in a group of physiological parameters including bone, liver metabolism and
      vascular activity, the Central nervous System (CNS,) the immune system and the
      skin. In the present work data about the molecular mechanisms involved will be
      presented. A total of 140 male and female rats have been submitted to different
      treatments over 10 weeks, between 22 and 24 months of age. Males have been
      treated with GH and Melatonin. Females were divided in two groups: intact and
      castrated at 12 months of age. The first group was treated with GH and Melatonin
      and the second with these two and additionally with Estradiol and Phytosoya.
      Aging was associated with a reduction in the number of neurones of the Hylus of
      the dentate gyrus of the hypothalamus and with a reduction of neurogenesis. GH
      treatment increased the number of neurones but did not increase neurogenesis thus
      suggesting a reduction of apoptosis. This was supported by the reduction in
      nucleosomes and the increase in Bcl2 observed in cerebral homogenates together
      with an increase in sirtuin2 and a reduction of caspases. Melatonin, estrogens
      and phytosoya treatments increased neurogenesis but did not enhanced the total
      number of neurones. On the liver, aging induced a signi-ficant increase in
      mitochondrial nitric oxide, an increase in cytochrome C in the cytosolic fraction
      and a reduction in the mitochondrial fraction thus inducing apoptosis as
      confirmed by the increase in caspases. Treatment for 2.5 months of old rats with
      GH and melatonin were able to significantly reduce the enhanced and increase the
      reduced values reducing apoptosis. A reduction in glutathione peroxidase and
      glutathione S-transferase was found also in old control rats when compared with
      the group of young animals. Keratinocytes from old rats in culture showed an
      increase in nucleosomes and a reduction in Bcl2 that was restored with GH and
      Melatonin. In conclusion, the mentioned hormonal treatment seems to have
      beneficial effects against age-induced damage in the CNS the liver and the skin
      through molecular mechanisms reducing oxidative stress and apoptosis.

PMID- 17451100
TI  - [Prenetal diagnosis: analysis of combined screening for first trimester].
AB  - Nowadays we are wittness of an outstanding increment in social demand related to
      prenatal diagnosis and genetic counsuelling. New life-style features have
      determined the sharp rise in pregnancies in women over 35 years of age. In this
      context, a recent interest on the risk of hereditary syndromes has developed.
      Only a few years ago, prenatal screening depended exclusively on epidemiologic
      data: age, and clinical past history. Due to a poor efficacy of these parameters,
      a new screening method based on sonographic and biochemical features is now
      considered to be mandatory. We describe our results of San Carlos Clinical
      Hospital including 4886 patients submitted to sonographic and biochemical
      screening during the first trimester of gestation, with a high sensitivity,
      acceptable false positive rate and a low cost/benefit rate. This information will
      determine an earlier decision making proccess, which will benefit both the mother
      and the fetus.

PMID- 17451101
TI  - [Chronic heart failure treatment in the year 2006].
AB  - Heart failure (HF) has a high incidence, near 2% of the population suffered this
      process, that increases with the age, affecting between 15-20 % of the population
      elder than 70 years. In the last 20 years the knowledge in pathophysiological
      mechanisms has improved, mainly, the role of neurohormonal response in the
      development and worsening of HF. In the last 15 years the efficient blockade of
      these mechanisms have improved the follow-up of these patients. The use of
      Angiotensin Converting Enzyme inhibitors, angiotensin II receptor blockers, Beta
      blockers and antialdosteronic drugs have significantly decreased cardiovascular
      morbidity and mortality of these patients. Nevertheless 50% of patients with HF
      dies for electrical disturbance of the ventricular rithm, tachycardia and
      ventricular fibrillation. Also, disorders of intraventricular conduction worsen
      the functional degree. The implantable cardioverter defibrillator reduce
      mortality in patients at higher risk for mortality due to HF and Cardiac
      Resynchronization Therapy may lead to remarkable improvement in clinical status
      in selected patients with HF. Other measures, as cardiac transplantsand
      implantable left ventricular assist devices are becaming more exceptional in all
      occidental countries. Cell transplantation is an innovative technology and has
      the potential to revolutionize alternative therapeutic approaches to management
      of heart failure, but still a numkber of problems persist before the extending
      use of these techniques.

PMID- 17451102
TI  - [The primordial reservoir in the infectious contagion cicle. The avian influenza
      model].
AB  - An update of the role of the primordial reservoir in the biological cycle of the
      process of infection and contagion is made, using diseases of very frequent
      incidence at the present moment in the Mediterranean Area and the Iberian
      Peninsula. These diseases are, amongst others Severe and Acute Respiratory
      Syndrome (SARS), Rabies, Lyme disease, African Horse Sickness, Blue Tongue,
      African Swine Fever, Ebola Hemorrhagic Fever, Hantavirosis, and Avian Influenza.
      The zoonoses classification proposed by the WHO Control Center in Athens in 1994
      for the Mediterranean Area, based on the type of reservoir, the importance of the
      process and the type of transmission, and not focusing on the etiological agent,
      is very positively valued. Finally, the problem of Avian Influenza and the real
      risk posed by aquatic migratory birds in the diffusion and contagion of the
      present Avian Influence epidemics is reviewed.

PMID- 17451103
TI  - [CT-PET: a new light in the diagnostic tunnel].
AB  - Positron Emission Tomography (PET) has got an important role in oncology. Since
      its introduction in 1995, more than 40 PETs have been installed in Spain. New
      hybrid CT-PET equipment that have appeared in the last three years have the
      anatomical and functional information of both techniques. The addition of CT
      makes it possible to reduce the duration of the PET study, to ameliorate the
      image quality, to ameliorate its diagnostic performance and to increase its
      indications. The new equipment being installed are all CT-PET and they will soon
      be more numerous than the previous PETs.

PMID- 17451104
TI  - [Surgery of the thyroid nodule. Current treatment].
AB  - The concept of "thyroid nodule" is the presence in the gland of a neoformation
      with an enough diameter in order to be palpable. From a clinical point of view,
      the problem relies in establishing its diferential diagnosis with the cancer
      which prevails between the 10-15% of the cases. We emphasize the diagnostical
      tests, the different accesses and the surgical treatments with a morbidity that
      focus the attention of the surgeon. Finally, the author will present its
      experience.

PMID- 17451105
TI  - [Spa therapy in depresive status and undercover depressions].
AB  - The actual interest of Spa Therapy in Depressive states and Undercover depression
      has been tested in the centers of several countries and its effects have been
      considered of great value in this pathologic processes. This hydrothermal
      treatment determines subjective improvements in a high percentage of the patients
      and helps the implantation of an effective psychotherapy.

PMID- 17451106
TI  - [Women the thought and works of Cajal (remembrances on the 100th anniversary of
      the Nobel Prize Award)].
AB  - This conference begins with a personal evocation of the author's grandfather,
      Gaspar Cruz y Martin, Anatomic Sculptor at the Faculty of Medicine of San Carlos-
      the commemorative medal depicting Cajal that can be seen today at the Cajal
      Teaching Room Museum in the Medical College of Madrid is due to his hand. The
      talk goes on to compile a little anthology of texts on women by Cajal, chosen as
      literary counterparts to his scientific writings. Women are seen by Cajal under
      the light of beauty, love, marriage, family and even feminism. The anthology ends
      with a series of "misogynistic stings"--as Dr. Cruz y Hermida calls them--which
      alternate negative criticism with open praise, mostly showing the admiration that
      women caused in the sensitive intelligence of the great humanist. The conference
      finishes with an account of the last moments of Cajal and the moving words by D.
      Teofilo Hernando, who was at the side of the Maestro when he passed away.

PMID- 17451107
TI  - Studies on persisting effects of soy-based compared with amino acid-supplemented
      casein-based diet on protein metabolism and oxidative stress in juvenile pigs.
AB  - Juvenile growing pigs were studied to explore whether a soy-based diet can induce
      persistent physiological alterations, especially in protein and energy
      metabolism, nutrient oxidation and redox homeostasis. In former studies we have
      shown that in juvenile pigs chronically fed protein diets based on either casein
      (CAS) or soy protein isolate (SPI), the SPI diet significantly decreases growth
      rate and increases oxidative stress responsiveness as compared to CAS. In
      addition, here we show that chronic feeding of SPI vs. CAS diet decreases whole
      body protein synthesis (WBPS) (p = 0.007) and hepatic gene expression associated
      with protein synthesis. To study persistent SPI effects, a three-period feeding
      experiment was designed: In the test group 18 pigs received the CAS diet for 24
      days (period 1), followed by 31 days on the SPI diet (period 2) and further 31
      days on the CAS diet (period 3). In the control group 18 pigs were fed the CAS
      diet throughout the three periods (86 days). Temporary consumption of SPI diet
      results in persistent changes of protein metabolism and oxidative stress
      responsiveness. After switching back from SPI to CAS diet the decrease of WBPS of
      the test group vs. control group was of borderline significance (p = 0.061),
      transcript levels of hepatic gene expressions of leucine aminopeptidase,
      endopeptidase 24.16, glutathione-S-transferase and peptide methionine sulfoxide
      reductase were increased. In liver tissue, total glutathione was increased and
      thiobarbituric acid reactive substances were decreased in the test vs. control
      group. In conclusion, results suggest that SPI-induced changes in protein and
      amino acid metabolism as well as in redox homeostasis and antioxidative potential
      in growing pigs persist 4 weeks after the cessation of SPI feeding.

PMID- 17451108
TI  - Comparison of a xylanase and a complex of non starch polysaccharide-degrading
      enzymes with regard to performance and bacterial metabolism in weaned piglets.
AB  - Weaned piglets were fed a wheat based diet either non-supplemented or
      supplemented with a multi-enzyme preparation or a xylanase mono-enzyme
      preparation, respectively. Both enzyme preparations increased live weight gain
      nonsignificantly, but only animals of the xylanase group showed a trend (p =
      0.076) for an improved feed conversion. Only precaecal digestibility of total
      amino acids was improved significantly when the mono-enzyme preparation was
      added. Improvements of digestibility of crude fat, crude protein and starch did
      not reach the significance level. Both enzyme preparations reduced jejunal
      viscosity, however viscosity in the colon was only reduced by the mono-enzyme
      preparation. Both enzymes significantly reduced Lactobacillus spp. cell numbers
      as well as bacterial metabolites in the stomach and showed similar nonsignificant
      modifications in jejunum contents except for acetate in the mono-enzyme group.
      Total jejunal bile acids were unchanged. Compared to the control, the ratio of
      the main conjugated to the main deconjugated bile acid was significantly higher
      in the mono-enzyme group. This study has shown that the mono- and multi-enzyme
      preparation can lead to improved performance in wheat based diets for piglets.
      Like in poultry, the main mode of action seems to be the reduction of small
      intestinal viscosity. However, the generation of fermentable carbohydrates by the
      multi-enzyme preparation may mask beneficial effects on performance due to the
      development of an active bile acid deconjugating microbiota in the small
      intestine.

PMID- 17451109
TI  - Prediction of utilizable true protein of mixed rations for sheep using an in
      vitro incubation technique.
AB  - The objective of the present experiment was to study the relationship between in
      vitro utilizable true protein (uTP) and in vivo-uTP of sheep rations by
      regression analysis. A further aim was to analyse if in vivo-uTP of mixed rations
      could be predicted by regression analysis between in vitro-uTP and in vivo-uTP,
      using N-retention of sheep as important evaluation criteria of protein value.
      Three adult male sheep (body weight [BW] 46 + 1.3 kg) fitted with rumen cannulas
      and simple T-type duodenal cannulas were fed with twelve typical rations with
      graded levels of crude protein and true protein in four experiments according a 3
      x 3 Latin square design. Each experimental period included an adaptation (7
      days), a N balance trial (4 days) and a collection of duodenal digesta (3 days).
      During collection of duodenal digesta, polyethylene glycol and chromium oxide
      were used as dual markers for the measurement of duodenal digesta flow and
      calculation of the in vivo-uTP of duodenal digesta. The in vitro-uTP of the
      rations was determined using the in vitro incubation technique of Zhao and
      Lebzien (2000). It was found that both in vitro-uTP intake and in vivo-uTP intake
      were significantly correlated with N-retention (p < 0.001) and that there was a
      significant linear relationship between the content of in vitro-uTP and in vivo
      uTP in rations (p < 0.001). Therefore, it was concluded that the used in vitro
      incubation technique is suitable for the determination of in vitro-uTP of mixed
      rations for sheep, and that the amount of in vivo-uTP can be predicted by
      regression between in vitro-uTP and in vivo-uTP.

PMID- 17451110
TI  - Fermentation of plant cell walls by ruminal bacteria, protozoa and fungi and
      their interaction with fibre particle size.
AB  - The objective of the experiment was to evaluate the contribution of various
      ruminal microbial groups to the fermentation of cell walls of corn stover with
      different particle sizes based on ruminal gas production in vitro. Physical,
      chemical, and antibiotical methods were used to differentiate groups of bacteria,
      protozoa and fungi in rumen fluid, offering following rumen microbial groups:
      whole rumen fluid (WRF), bacterial (B), protozoal (P), fungal (F), bacterial plus
      protozoal (B + P), bacterial plus fungal (B + F), protozoal plus fungal (P + F),
      and negative control (CON). Cell walls from corn stover were ground and ball
      milled to produce two different particle sizes. The results showed that digestion
      of the cell walls was undertaken by the interaction among ruminal bacteria,
      protozoa and fungi, and such co-actions seemed to fail alternation by one of
      three microbial groups or any combinations. However, B + P group showed a
      significant contribution to the degradation of milled cell walls, and B + F group
      revealed a great synergy effect on the ground cell walls degradation. Particle
      size of cell walls also had a considerable influence on their fermentation extent
      instead of the fermentative patterns by various rumen microbial groups.

PMID- 17451111
TI  - Effects of dietary mannanoligosaccharide on performance, some blood parameters,
      IgG levels and antibody response of lambs to parenterally administered E. coli
      O157:H7.
AB  - Forty-eight male lambs were used to evaluate the effect of dietary
      supplementation of mannanoligosaccharide (MOS) with or without parenteral
      Escherichia coli injection on their growth performance, feed conversion
      efficiency, blood metabolites, total serum immunoglobulin G (IgG) levels and
      antibody response. Lambs were randomly assigned to four groups of 12 animals
      each. In groups C (control) and CE (E. coli challenged), animals were fed
      commercial concentrate pellets and hay (50:50), and in groups M (MOS) and ME (MOS
      + E. coli challenged), animals were fed commercial concentrate pellets including
      MOS at 0.2% and hay (50:50). At day 15 and 30, animals in groups CE and ME were
      injected subcutaneously with 1 ml of phosphate buffered saline (PBS) suspension
      containing 10(6) cfu of heat inactivated non-toxigenic E. coli O157:H7, while
      animals in C and M groups were injected subcutaneously with 1 ml of PBS. The
      experimental period was 45 days. Data indicated that body weight of lambs at the
      end of the study were statistically non-significant among the groups. Blood
      metabolites, i.e. total protein, albumin, calcium and phosphorus concentrations
      were not affected significantly by MOS supplementation. However, administration
      E. coli lowered (p < 0.05) total protein, albumin and calcium concentrations in
      the serum on day 30. The IgG level was not different between groups. However, on
      day 45, the total IgG level was found to be higher (p < 0.05) in lambs that had
      received MOS and E. coli than in other groups. Application of MOS did not have
      any effect on the antibody response to E. coli as OD values.

PMID- 17451112
TI  - Effect of dietary conjugated linoleic acid and selenized yeast on the
      concentration of fatty acids and minerals in rats.
AB  - The main objective of this study was to evaluate the influence of diets enriched
      in individual conjugated linoleic acid (CLA) isomers, their mixture, and/or
      selenized yeast (Se-yeast) on the concentration of CLA isomers, long-chain
      polyunsaturated fatty acids (PUFA) and Se in the heart, muscles and liver of
      rats. The investigation was performed on 73 female Wistar rats (8 weeks of age,
      200 g initial BW). After one week sub-maintenance feeding, rats received diets
      supplemented with 1% individual CLA isomers or 1 or 2% of a CLA isomers mixture,
      without or with 1.2 mg Se/kg (as Se-yeast) for 29 days. Feeding diets with 2% CLA
      isomer mixture reduced feed intake and body weight gain of rats, while addition
      of trans10,cis12 CLA and Se-yeast resulted in the highest body weight gain. CLA
      supplementation generally elevated the concentration of CLA isomers in heart and
      muscles significantly, although cis9,trans11 CLA accumulated preferentially.
      Regardless of the presence of Se-yeast, the dietary enrichment with CLA isomers
      caused a reduction in the capacity of A9-desaturase. Addition of Se-yeast to
      diets with individual CLA isomers or a 1% mixture of CLA isomers elevated the
      accumulation of CLA isomers in the heart and muscles, whereas all treatments with
      supplemented CLA and Se-yeast increased the accumulation of Se in rats compared
      with animals fed the diet containing Se only. Furthermore, CLA isomer
      supplementation decreased the concentration of PUFA and total fatty acids in the
      heart and muscles compared with control rats. Moreover, addition of CLA isomers
      interfered in the conversion of linoleic and linolenic acids to higher
      metabolites due to competition of CLA isomers for the same enzymes (delta6-,
      delta5-, delta4-desaturases and elongase).

PMID- 17451113
TI  - The content of protein, fibre and minerals of leaves of selected Acacia species
      indigenous to north-western Tanzania.
AB  - Browse tree leaves of six species of Acacia (A. angustissima L., A. drepanolobium
      L., A. nilotica L., A. polyacantha L., A. senegal L., A. tortilis L.) were
      screened for chemical composition, including minerals and trace elements. Crude
      protein (CP) varied among the species from 145 (A. senegal) to 229 g/kg DM (A.
      angustissima). The species had moderate to high levels of minerals. The
      concentrations of Ca, P, Mg and S varied among the species from 14.6-31.5, 3.5
      4.9, 1.4-3.0 and 1.7-2.8 g/kg DM, respectively. The forages showed relatively low
      concentrations of trace elements. Content of trace elements varied among the
      species from 4.5-23.8, 99.4-173.6, 146.2-432, 41.0-90.1, 10.9-22.2 and 0.05-0.65
      mg/kg DM for Cu, Mo, Fe, Mn, Zn and Co, respectively. All leaves of browse
      species would meet the normal requirements for Ca, P, Mg and S in ruminants,
      although some species had higher levels of Ca than tabulated mineral requirements
      in livestock. Assayed Cu, Mn, Zn and Co would satisfy the lower range of
      recommended requirements of trace elements depending on their bioavailability.
      Therefore, browse leaves from Acacias could form good sources of CP and mineral
      supplements to ruminants.

PMID- 17451114
TI  - [A medieval herbal from the 14th century, a new version of the Latin Macer?].
AB  - A medical compendium of "Melleus liquorphysicae artis" has survived under the
      name Alexander Hispanus; it is in codex Ms. 8769 of the Biblioteca nacional in
      Madrid. Therein a herbal from the 14th century is integrated. However, today
      people must think that we have one herbal and two authors: Alexander Hispanus and
      Henrik Harpestraeng (died 1244), a physician from Scandinavia. First of all, the
      parts of the medical compendium are presented. We do not know which parts
      originally belong to the medical compendium. The examination of many handwritings
      suggested that the discourses about consumption and dropsy were not originally
      included in the compendium; that seems certain. Further it was shown that
      probably Alexander Hispanus did not live after all and we must see him as a
      fictional person. Nevertheless we should not automatically regard Henrik
      Harpestraeng as the author of the herbal although it contains typical plants of
      the North like Angelica. The oldest codex of the herbal was probably written in
      Bavaria or Austria because it contains old Bavarian words. This handwriting can
      be seen as a piece of evidence that the knowledge about Angelica was spreading
      from the South. We should explore the connection with handwritings of the Macer,
      too. The herbal could be a Latin version of the Macer, in which the original
      verses are abandoned. An analysis of the medical plants made it clear that the
      herbal is probably directed to a male readership. Especially the chapter on
      Galganum elucidates that. In the 14th century Galganum was thought to have a
      contraceptive effect, but this was kept secret from women! All in all the
      structure of the herbal suggests a use as a kind of reference book that was not
      used daily though.

PMID- 17451115
TI  - [Teaching at the University of Jena as a contribution to the German debate about
      Lavoisier's chemistry].
AB  - The German debate about Lavoisier's chemistry started late, was confined to the
      theory of combustion, mainly focused on two experiments and was closed relatively
      soon. The perspective from academic teaching allows a better understanding of
      these features. There was a far-reaching correspondence between the usual
      practice of academic chemistry teachers and the epistemic criteria taken to be
      relevant during the debate about Lavoisier's chemistry. A case study based on
      textbooks written or used at the University of Jena between 1790 and 1800 allows
      drawing conclusions about why and how academic chemists succeeded in integrating
      what was seen as the "chemical revolution" without revolutionising their own
      practice. If the debate had any profound impact on German chemistry at all, it
      was the consolidation of the rupture between academic teachers and their
      apothecary colleagues.

PMID- 17451116
TI  - [Wilhelm Heinrich Schussler's healing system "Biochemie" and its further
      development by Dietrich Schopwinkel].
AB  - The German Physician Wilhelm Schussler (1821-1898) developed a healing system
      called "Biochemie". Basically it had merely the character of a substitution
      therapy with mineral compounds and was based on physiological considerations by
      Jakob Moleschott (1822-1893) and Justus von Liebig (1803-1873) which were
      fundamental for the development of the scientific discipline of biochemistry as
      well. Schussler himself, however, who had been educated in homoeopathy,
      introduced more and more immaterial or "biodynamic" explanations for the
      therapeutic effect of the mineral salt preparations. This attempt was continued
      by his successors, namely by Dietrich (called Dieter) Schopwinkel (1876-1946) who
      enriched the system with new preparations as well as several theoretical aspects
      strongly related to the dynamic approach.

PMID- 17451117
TI  - [Henri Ellenberger, Henri Ey and the Traite de Psychiatrie in the "Encyclopedie
      Medico-Chirurgicale": an American career under the auspices of the "Evolution
      Psychiatrique"].
AB  - Henri Ellenberger, psychiatrist and historian, experienced a decisive period in
      his career in the early fifties of the last century. Educated in France, intern
      at Sainte-Anne Hospital, he was working in Switzerland after the war and then
      tried to move to the United States. It was during his participation in the French
      group "l'Evolution Psychiatrique" that he happened to contribute to the treatise
      of psychiatry (1955) of the French medical and surgical encyclopaedia ("EMC") and
      organise an observation trip to the United States. He was supported at that time
      by Henri Ey, key figure of French psychiatry. While going back to his career, we
      would like to emphasise on his comments about the "Psychotherapy of
      schizophrenia". Even though later Ellenberger became a well-known researcher in
      North America, it is more a question for us to discuss the scientific ambition he
      had in this particular context of a French learned society as a member of
      "l'Evolution Psychiatrique" and as a psychiatrist formerly intern from the
      "Hopitaux psychiatriques de la Seine" (Parisian district).

PMID- 17451118
TI  - [Natural history in the 16th Century: historiography, methodology, and
      perspectives].

PMID- 17451119
TI  - Comparing the microdebrider and standard instruments in endoscopic sinus surgery:
      a double-blind randomised study.
AB  - Comparing the microdebrider and standard instruments in endoscopic sinus surgery:
      a double-blind randomised study. OBJECTIVE: It is frequently stated that
      microdebriders provide better mucosal preservation in endoscopic sinus surgery
      (ESS), and therefore better and faster healing, when compared to the standard
      Blakesley instruments. However, evidence from comparative prospective studies is
      lacking. In this study, we compared the results of microdebriders with
      traditional surgical instruments for ESS. METHODS: A prospective, randomised,
      comparative, double-blind study in 50 patients undergoing bilateral ESS. Each
      patient was operated on with both instruments: one side of the nose with the
      microdebrider only, and the other side with standard instruments. The outcome of
      surgery was measured by using a symptom score and an endoscopic score at five
      time points during the first six postoperative months. RESULTS: Both instruments
      resulted in symptom improvement and in endoscopically visible healing over time,
      but no significant difference was found between the two techniques. In endoscopic
      evaluation, only the total score at 3 weeks after surgery was significantly
      better in the microdebrider group. No significant difference was found at any
      other time point. Synechia formation, patency of middle meatal antrostomy, and
      open access to the ethmoid were the same in both groups. CONCLUSION: In this
      study of endoscopic sinus surgery the use of the microdebrider does not offer
      major advantages compared to the standard instruments.

PMID- 17451120
TI  - Today's indications for cochlear implantation.
AB  - Today's indications for cochlear implantation. During the last twenty years, the
      indications for cochlear implants (CIs) extended significantly due to positive
      experience with CIs, improved CI technology, and safer surgery. This paper
      reviews the classical and emerging indications for CIs anno 2007. Providing a
      postlingually deaf adult with a unilateral CI has been the earliest indication
      and remains the standard indication. However, CIs are also indicated for
      prelingually deaf adults, and for children younger than one year old. Recently,
      CIs are also indicated for adults with residual hearing: when best aided sentence
      recognition scores in quiet are lower than 70%. CIs for patients with residual
      hearing sometimes imply the use of a bimodal CI; a device that stimulates the
      cochlea both electrically and acoustically. Another promising evolution is
      bilateral implantation. Nowadays, it has also become possible to place a CI in
      the malformed cochlea. When an auditory nerve is absent or when implantation
      failed despite a functional device, auditory brainstem implants can restore some
      form of hearing to the deaf.

PMID- 17451121
TI  - The effect of very low birth weight on otoacoustic emissions.
AB  - The effect of very low birth weight on otoacoustic emissions. OBJECTIVES: The aim
      of this study was to examine the effect of very low birth weight (VLBW) on the
      measurement of transiently evoked otoacoustic emissions (TEOAEs) in newborns.
      METHODS: TEOAEs were recorded in all VLBW newborns (birth weight < 1500 g) who
      were admitted in the Neonatal Intensive Care Unit of the Iaso Maternity Hospital,
      during a period of 1 year. Twenty-four VLBW newborns were included in the study.
      Their mean birth weight was 1283 g and they had mean gestational age 31.3 weeks.
      Forty full-term newborns with absence of any risk factor for hearing impairment
      were used as controls. RESULTS: TEOAEs were present in 97.5% of controls, but
      only in 79.2% of the VLBW group. Statistically significant differences were found
      between VLBW newborns and controls in most TEOAE measures. CONCLUSIONS: Increased
      rate of initial 'fail' in hearing screening, in conjunction with statistically
      confirmed lower TEOAE measures in VLBW newborns, justifies special care and long
      term follow-up for this group of newborns.

PMID- 17451122
TI  - Case-report: metastasizing pleomorphic adenoma of the parotid gland.
AB  - CASE-REPORT: Metastasizing pleomorphic adenoma of the parotid gland. We present a
      case of metastasizing pleomorphic adenoma (MPA). The patient died in 2002 at the
      age of 64 years, following on an initial diagnosis of a pleomorphic adenoma of
      the right parotid gland at the age of nineteen, multiple local recurrences and
      finally rib metastases. Histological examination of the excised tissue from the
      parotid gland and the metastases showed it to be a pleomorphic adenoma without
      any signs of malignancy, although the metastatic deposits consisted mostly of a
      myoepithelial component. Both in our case as in most of the literature, MPA
      follows a probable incomplete removal of the first tumour. We conclude that the
      first operation is of great importance for the prevention of late recurrences and
      metastatic spread.

PMID- 17451123
TI  - Carcinoma ex pleomorphic adenoma of the submandibular gland with distant
      metastases.
AB  - A case of metastatic carcinoma ex pleomorphic adenoma (PA) of the submandibular
      gland is reported. While reports of local recurrence of this cancer are numerous,
      few cases of distant metastases have been reported. We report a case of a 52-year
      old male patient with a history of PA diagnosed ten years previous. The patient
      presented reporting that the mass had increased size and pain during the previous
      six months. Needle biopsy results of this mass were compatible with a poorly
      differentiated carcinoma of the salivary ducts. Radical surgery with wide right
      neck dissection was performed with curative intent. Three years post-surgery
      liver and bony metastases were detected. In conclusion, the potential for
      malignant transformation of PA demands close follow-up of younger patients.

PMID- 17451124
TI  - An unrecognized foreign body in the parotid gland after trauma.
AB  - OBJECTIVE: Foreign bodies within the parotid gland retained after trauma are
      rarely observed, due in part to ease of detection. Few, however, particularly
      wooden foreign bodies, may not be identified clinically and radiologically. CASE:
      A 44-year-old male was admitted complaining of recurrent swelling and pain in the
      left parotid gland with recent history of penetrating parotid trauma and foreign
      body removal. Ultrasonography revealed a high degree of parenchymal heterogeneity
      and an 18 x 5.7 mm linear mass shadow. Following superficial parotidectomy, an
      approximately 1 x 2 cm wooden fragment that was buried in the masseter muscle and
      surrounded by granulation tissue was palpated and extracted. CONCLUSION: Any
      suspicion of a residual foreign body after penetrating parotid gland trauma can
      be clarified with a detailed radiological examination, which may provide further
      guidance for treatment. The treatment modality of parotid foreign bodies is early
      surgical exploration, and in delayed cases, superficial parotidectomy may be
      needed.

PMID- 17451125
TI  - Fibrous dysplasia of inferior turbinate, middle turbinate, and frontal sinus.
AB  - Fibrous dysplasia (FD) is a non-neoplastic fibro-osseous lesion. Paranasal sinus
      involvement is infrequent. Involvement of the frontal sinus, sphenoid sinus, and
      middle turbinate is rare, and only sporadic cases have been reported in the
      literature. Nasal turbinates and especially the inferior turbinate are the least
      involved bones of the craniofacial region. To the best of our knowledge, only one
      case with McCune-Albright syndrome had FD of the inferior turbinate. Here, we
      report a rare case with FD of inferior and middle turbinates and review
      literature concerning FD of the craniofacial region.

PMID- 17451126
TI  - Management of second branchial cleft abnormalities in adults.
AB  - OBJECTIVE: Branchial cleft anomalies are developmental disorders of the neck. Our
      aim is to report the diagnostic and treatment procedure followed in three cases
      of second branchial cleft abnormalities in adults. METHODOLOGY: A patient aged
      over 40 underwent surgical excision of a well-encapsulated cystic neck structure
      and two further patients of a branchial sinus and branchial fistula respectively.
      Prior to surgery the patients were assessed by means of imaging techniques, FNA
      cytology and cytometric DNA analysis. RESULTS: Neutrophils, debris, mature
      squamous epithelial cells including degenerate forms and lymphoid cells were the
      key features in the cytological diagnosis. DNA analysis of the pre-operative
      cytological material in two cases revealed euploidy, thus indicating no
      malignancy. Histological examination of the lesions after excision established
      the diagnosis in all cases. No recurrences were reported. CONCLUSIONS: Although
      congenital lesions, the second branchial cleft abnormalities usually present in
      adulthood and have to be distinguished from benign and malignant lateral neck
      swellings. FNA cytology as well as DNA ploidy determination contributes to the
      establishment of the diagnosis of branchial cleft abnormalities and their
      differential diagnosis.

PMID- 17451127
TI  - Squamous cell nose and a synchronous in-situ vocal cord carcinoma: a case report.
AB  - Reports indicate that the incidence of multiple primary tumours in head and neck
      cancers is high. However, most of these tumours are either metachronous primary
      or secondary tumours of the same histopathological type. The development of a
      synchronous primary squamous cell skin cancer of the nose and an in-situ vocal
      cord carcinoma is something unusual. We present the case of a patient with a
      primary neoplasm along the lateral side of the nose up to the bone of the
      pyramid, including the skin of the inner side of the nose and an infiltration of
      the inferior nasal concha on the right side, together with a small synchronous
      primary lesion of the left vocal cord. To the best of our knowledge the case
      described is the first in the English medical literature and we discuss the
      complete management of synchronous head and neck malignancies, emphasising the
      importance of panendoscopy in the prevention of pitfalls in diagnosis and the
      therapeutic procedure.

PMID- 17451128
TI  - Sigmund Freud's physicians and "the monster".
AB  - Freud received treatment from several physicians--including rhinologists, oro
      facial surgeons or radiotherapists--for a cancer of the palate. Furthermore, as a
      consequence of his operation, Freud was required to wear a prosthesis that he
      probably named "the monster". This paper provides some details about the
      physicians who cured Freud and looks at the prosthesis he was forced to wear
      until his death.

PMID- 17451129
TI  - Birth certificates are an inappropriate source for identifying cases of birth
      defects in epidemiologic studies.

PMID- 17451130
TI  - The Center for Alaska Native Health Research Study: a community-based
      participatory research study of obesity and chronic disease-related protective
      and risk factors.
AB  - OBJECTIVES: To describe the background, approach and general results of the
      Center for Alaska Native Health Research (CANHR) study. STUDY DESIGN: This was a
      cross-sectional Community-Based Participatory Research (CBPR) study with one
      tribal group to assess risk and protection for obesity and the risk factors
      related to chronic disease, diabetes and cardiovascular disease. METHODS: A
      combination of biological, genetic, nutritional and psychosocial measurements
      were taken on 922 Alaska Native participants in ten communities in Southwestern
      Alaska. The paper reports on data from 753 adult participants. RESULTS: The
      prevalence of type 2 diabetes is 3.3% in the sample population. Metabolic
      syndrome is significantly lower among the males and equal for females when
      compared with Caucasians in the NHANES III sample. Obesity among adults is now at
      the national average. Risk factors for chronic disease include a shift to a
      Westernized diet, stress, obesity and impaired fasting glucose and protective
      factors include high levels of polyunsaturated fatty acid dietary intake.
      Articles in this issue present specific results in these areas. CONCLUSIONS: The
      data strongly indicate that, in general, Yup'ik people in our study are
      metabolically healthy and that diet and life style provide a delicate combination
      of protective and risk factors. The results strongly indicate that solution
      focused research utilizing primary and secondary prevention strategies may
      provide evidence for how to intervene to prevent further increases of chronic
      diseases. Research that focuses on relating the intrinsic strengths of indigenous
      worldviews and practices with basic research may contribute to positive
      transformations in community health.

PMID- 17451131
TI  - Sharing results from complex disease genetics studies: a community based
      participatory research approach.
AB  - OBJECTIVES: Dissemination of research results to communities builds capacity of
      the community to understand and utilize the results. The objective of this
      manuscript was to propose a culturally appropriate approach to disseminate
      complex disease genetics research findings in small Alaska Native communities.
      STUDY DESIGN: The Center for Alaska Native Health Research is a community-based
      participatory research project (CBPR) directed at understanding the interactions
      between genetic, nutritional and psychosocial risk factors for obesity, diabetes,
      and cardiovascular disease in Yup'ik Eskimos. METHODS: We have consulted with
      regional healthcare providers, tribal leaders, and university-, local-, and
      national-institutional review boards to identify potential mechanisms for sharing
      population-based genetics research results or progress. RESULTS: We propose a six
      step CBPR-approach to conducting genetics research in isolated identifiable
      communities. This CPBR-approach includes generating a common research question,
      determining community interest, recruitment, capacity building, sharing power and
      control, avoiding group harm, and development of culturally appropriate
      dissemination procedures. CONCLUSIONS: Research scientists and community members
      should both benefit from population-based genetics research. Although we are just
      beginning our discussions with regard to sharing genetics research progress and
      findings, we believe that it is essential move forward as co-researchers in the
      CBPR enterprise.

PMID- 17451132
TI  - Age-related variation in red blood cell stable isotope ratios (delta13C and
      delta15N) from two Yupik villages in southwest Alaska: a pilot study.
AB  - OBJECTIVES: A significant fraction of the Alaska Native population appears to be
      shifting from a primarily subsistence-based diet to a market-based diet;
      therefore, the ability to link diet pattern to disease risk has become
      increasingly important to predicting public health needs. Our research aims to
      develop the use of stable isotope ratios as diet pattern biomarkers, based on
      naturally-occurring isotopic differences in the elemental composition of
      subsistence and non-subsistence foods. These differences are reflected in human
      blood, hair and fingernail isotope signatures. STUDY DESIGN: In this preliminary
      study, we investigate the potential for 13C and 15N to serve as dietary
      biomarkers for age-related dietary differences in a subset of participants
      involved with a long-term study initiated by the Center for Alaska Native Health
      Research (CANHR) at the University of Alaska Fairbanks (UAF). METHODS: We
      measured delta13C and delta15N in red blood cells collected from 12 "elder"
      participants (age 60+ yrs) and 14 younger participants (age 14-19 yrs). Samples
      were evenly divided between males and females, and between two villages sampled
      in 2004. We also sampled market and subsistence foods in Fairbanks, AK, as an
      indicator of the isotopic differences likely to be observed in village foods.
      RESULTS: Elders were significantly enriched in 15N, but depleted in 13C, relative
      to younger participants. These differences are consistent with increased intake
      of marine subsistence in elders, and of certain market foods in younger
      participants. However, elders were considerably more variable in delta15N,
      suggesting greater differences among individuals in their usual intake.
      CONCLUSIONS: Overall we find that RBC stable isotope signatures exhibit variation
      consistent with previously documented dietary patterns in Alaska Natives, and we
      describe future directions for developing these biomarkers for diet pattern
      monitoring.

PMID- 17451133
TI  - Keeping busy: a Yup'ik/Cup'ik perspective on health and aging.
AB  - OBJECTIVES: Knowledge of cultural beliefs about health and how they influence
      life choices and intervention is essential in forming health policy and health
      promotion programs to meet the growing needs of aging minority populations. This
      study explores cultural beliefs and practices of health and well-being of
      Yup'ik/Cup'ik women in two rural villages in southwestern Alaska. STUDY DESIGN:
      Exploratory, descriptive qualitative study. METHODS: Interviews were conducted
      with 15 mid-life and older women to address two key research questions: 1) How do
      Yup'ik/Cup'ik women define health and wellbeing; and 2) What environmental,
      social, and cultural factors contribute to healthy aging? RESULTS: The women in
      this study define health aging within the framework of subsistence living-keeping
      busy, walking, eating subsistence foods, and respect for elders. These beliefs
      and practices promote a strong, active body and mind, vital components to healthy
      aging. CONCLUSIONS: While many health beliefs and practices appear very different
      from those current in research on aging, many commonalities and similarities
      emerge-concern for family, importance of physical activity and healthy diet. A
      significant finding of this study is that traditional Yup'ik/ Cup'ik ways of
      living parallel that of current research findings on what constitutes healthy
      aging in mainstream populations.

PMID- 17451134
TI  - Stress, coping, and well-being among the Yup'ik of the Yukon-Kuskokwim Delta: the
      role of enculturation and acculturation.
AB  - OBJECTIVES: To report on the relationships between cultural identity and stress,
      coping, and psychological well-being in Yup'ik communities. STUDY DESIGN: A
      quantitative self-administered questionnaire. METHODS: A health and wellness
      survey was completed by a total of 488 Yup'ik participants (284 women and 204
      men) from 6 rural villages in the Yukon-Kuskokwim Delta region. Respondents were
      fairly equally distributed across an age range of 14 to 94 (mean +/- SD = 38.50
      +/- 17.18). RESULTS: Participants who reported living more of a Kass'aq way of
      life (greater acculturation) reported experiencing greater psychosocial stress,
      less happiness, and greater use of drugs and alcohol to cope with stress.
      Participants who reported identifying more with a traditional Yup'ik way of life
      reported greater happiness, more frequent use of religion and spirituality to
      cope with stress, and less frequent use of drugs and alcohol to cope with stress.
      CONCLUSIONS: In conjunction with previous research, the data strongly indicates
      that in general, Yup'ik people in the Y-K Delta tend to associate stress and
      negative health outcomes with the process of acculturation, and health and
      healing with the process of enculturation. Research that focuses on documenting
      the intrinsic strengths of indigenous worldviews may contribute to positive
      transformations in community health.

PMID- 17451135
TI  - Nutrient intakes are associated with adherence to a traditional diet among Yup'ik
      Eskimos living in remote Alaska Native communities: the CANHR Study.
AB  - OBJECTIVES: To determine whether dietary westernization is associated with intake
      of select nutrients among Alaska Natives living in remote communities. To
      investigate participant characteristics associated with adherence to the
      traditional Alaska Native diet. STUDY DESIGN: Cross-sectional survey. METHODS: A
      24-hour recall was collected from 241 men and 307 women aged 14-94 years living
      in seven remote communities of Western Alaska. Bivariate analyses and ANOVA were
      used to examine the relationship between energy from traditional foods (the
      primary variable of interest), participant characteristics and intake of select
      nutrients. RESULTS: Traditional foods accounted for 22% of energy intake.overall.
      This estimate varied by age, educational attainment, and geographic location.
      Participants in the highest quintile of traditional food intake consumed
      significantly more vitamin A, vitamin D, Vitamin E, Iron, and n-3 fatty acids
      than participants in the lowest quintile (p < 0.001). Intake of vitamin C,
      calcium, and total dietary fiber decreased with increased consumption of
      traditional foods (p < 0.001). CONCLUSIONS: The degree of dietary westernization
      contributes to nutrient intake, both positively and negatively, in a dose
      response manner. Participant characteristics, particularly age, must be addressed
      in the development of a nutrition education program since they are associated
      with distinct dietary intakes.

PMID- 17451136
TI  - Social transition in the north: comparisons of drug-taking behavior among Alaska
      and Russian natives.
AB  - OBJECTIVES: This study represents a continuation of the work initiated by the
      "Social Transition in the North" (STN) project. This research extends the
      findings from earlier reports, specifically focusing on comparisons of drug
      taking behavior among Alaska and Siberian Eskimos; it is one of the first studies
      that obtained substance abuse data from Russian Natives in eastern Russian. STUDY
      DESIGN: The data were taken from the STN study was collected in two regions of
      Alaska (Northwest Arctic and the Aleutian Islands) and in two regions of the
      Russian Far East (Kamchatka and Chukotka). The health questionnaire included
      questions about the drug taking behavior of the study populations. METHODS: The
      methodology employed was responses to a questionnaire, administered by the
      initial Social Transitions team. Imbedded in the interview protocols were
      questions (in a quantitative format) that inquired about drinking and other drug
      use. Seven-hundred interviews, conducted the first year, formed the database for
      the findings reported herein. Of these respondents, 45% are Alaska Native; 55%
      are Russian Natives. Ages ranged from 13 to 60, with a mean of 38 years. Among
      the Alaskan group, 35% were male, 65% female; of the Russians, 25% were female,
      75% were male. RESULTS: The Russian cohort consumed significantly higher levels
      of alcohol, while the Alaskan group reported higher levels of marijuana, cocaine,
      inhalants and chewing tobacco. CONCLUSIONS: The differences found were
      attributable to cultural practices, reflected by the traditional drinking
      practices in Russian and to the rising substance abuse problem in the U.S.

PMID- 17451137
TI  - Epidemiology of Trichinella in Greenland--occurrence in animals and man.

PMID- 17451138
TI  - Insulin resistance-associated cardiovascular risk factors among Finnish men in
      military service--effect of smoking on risk factors.

PMID- 17451139
TI  - Is there a future for scientific medical libraries?

PMID- 17451140
TI  - Hypertension and the kidney.
AB  - The kidney could be the cause of essential hypertension which can also cause
      renal disease. High blood pressure is also very common in chronic kidney disease,
      and is moreover a well-known risk factor for a faster progression of kidney
      failure. Hypertension and kidneys are thus closely linked. Hypertension must be
      aggressively treated in patients suffering from chronic kidney disease, with a
      blood pressure goal of less than 130/80 mmHg, even lower than 125/75 mmHg when
      proteinuria is over 1g/day, using optimal and effective antihypertensive drugs.
      Among them, the blockers of the renin-angiotensin axis offer nephroprotective but
      also cardioprotective properties beyond their effect on blood pressure.

PMID- 17451141
TI  - The microcirculation in critically-ill patients.
AB  - The microcirculation plays a major role in oxygen delivery and organ perfusion,
      and is largely involved in the pathophysiological alterations of shock states. It
      has been a focus of research for a long time, but human clinical and
      physiological studies have been limited by a lack of reliable techniques
      available at the bedside. Intravital microscopy, although of interest in
      experimental studies, is not feasible in human studies. Laser Doppler techniques
      can measure blood flow, but do not take into account the heterogeneity of the
      microcirculation. Recently, the Orthogonal Polarized Spectral (OPS) imaging
      technique has enabled the study of the microcirculation in humans. This technique
      has allowed a better definition of microcirculatory alterations in disease
      states, defined the role of some medical interventions, and been used to predict
      outcome. In this text, we briefly describe the techniques available to study the
      microcirculation and review experimental and human studies in this domain.

PMID- 17451142
TI  - Systemic inflammatory diseases (SIDS), what's in a name.

PMID- 17451143
TI  - Diagnostic strategy in systemic inflammatory diseases.

PMID- 17451144
TI  - Guidelines for the transfusion of platelets.
AB  - Recommendations aiming at standardising and rationalising clinical indications
      for the transfusion of platelets in Belgium were drawn up by a working group of
      the Superior Health Council. To this end the Superior Health Council organised an
      expert meeting devoted to "Guidelines for the transfusion of platelets" in
      collaboration with the Belgian Hematological Society. The experts discussed the
      indications for platelet transfusions, the ideal platelet concentrate and the
      optimal platelet transfusion therapy. The recommendations prepared by the experts
      were validated by the working group with the purpose of harmonising platelet
      transfusion in Belgian hospitals.

PMID- 17451145
TI  - Implementing and optimising an Electronic Library of Health Care in Belgium:
      results of a pilot study.
AB  - Health care practitioners are expected to incorporate results from the best
      available, scientific information into their daily clinical decision-making
      process. Useful formats of evidence for practitioners include selected reviews,
      abstracts in which research results are discussed, "quick answer", evidence-based
      website including for example diagnostic and therapeutic algorithms, drugs
      prescription and non-drug therapy. An increasing amount of practitioners has
      access to the World Wide Web, either at home or at the office. However, easy and
      cheap access to objective and high quality research results is limited. Many
      practitioners lack the skills to efficiently navigate complicated medical
      databases. In 2003 an 'Electronic Library of Health Care' was introduced in
      Belgium. The main goal of the electronic library is to provide a gateway to
      scientific evidence to Belgian health care practitioners from different
      disciplines. This paper presents the results of a pilot project to implement the
      library in the field. It also describes recent developments and adjustments that
      increased the efficacy of this gateway to evidence.

PMID- 17451146
TI  - Aortic arch calcification predicts the extent of coronary atherosclerosis in
      patients with or without type 2 diabetes: short communication.
AB  - AIM OF THE STUDY: The aim of this study was to evaluate the sensitivity and
      specificity of aortic arch calcification for detection of severe coronary
      atherosclerosis in patients suffering from coronary artery disease (CAD), with or
      without type 2 diabetes. PATIENTS AND METHODS: This study included 107 type 2
      diabetic patients (68 men) with a mean age of 62.4 +/- 10.7 years and a mean
      diabetes duration of 14.2 +/- 5.9 years and 104 patients (63 men) with a mean age
      of 64.5 +/- 9.3 years who did not have diabetes. All patients had CAD, documented
      by coronary arteriography. Severe CAD was defined as atherosclerosis of the left
      main branch or atherosclerosis of three coronary arteries or atherosclerosis of
      the proximal part of the left anterior descending artery. Aortic arch
      calcification was assessed by means of posteroanterior chest X-rays, studied by a
      radiologist kept blind to the result of coronary arteriography. RESULTS: In type
      2 diabetic patients, diagnosis of aortic arch calcification had 65.6% sensitivity
      and 86.9% specificity for detection of severe CAD. In patients without diabetes,
      diagnosis of aortic arch calcification had 47.7% sensitivity and 96.7%
      specificity for detection of severe CAD. CONCLUSIONS: Aortic arch calcification
      has a high specificity for detection of severe coronary atherosclerosis in
      patients with CAD. Sensitivity is higher in patients with type 2 diabetes, while
      specificity is slightly higher in non-diabetic patients.

PMID- 17451147
TI  - Primary tracheobronchial amyloidosis: a series of 3 cases.
AB  - Primary tracheobronchial amyloidosis is a form of localized pulmonary
      amyloidosis, characterised by the deposition of AL-amyloid in trachea and
      bronchi. It is a rare and slowly progressive disease, usually requiring repeated
      endoscopic treatment. In this case series we describe symptoms, diagnostic and
      therapeutic procedures, radiological findings and pulmonary function testing in 3
      cases of different presentation and severity. Two patients were treated by
      endoscopic debulking and stent placement during rigid bronchoscopy, both with
      excellent clinical and functional results. In one of these patients regular
      endoscopic and clinical control exams were performed in the 5 years following the
      initial treatment, showing stable disease, requiring no further therapeutic
      intervention until today.

PMID- 17451148
TI  - Renovascular hypertension associated with neurofibromatosis: a case report.
AB  - Although vascular involvement in type 1 neurofibromatosis (NF1) is rare, it may
      lead to renal artery stenosis and renovascular hypertension (RVH). RVH may be
      treated using antihypertensive drugs, percutaneous transluminal renal angioplasty
      (PTRA), surgical reconstruction of the renal artery, or nefrectomy. In NF1 the
      results of PTRA are less predictable than in cases of fibromuscular dysplasia and
      atherosclerosis. We report a case of RVH associated with NF1. Despite
      administration of multiple antihypertensive drugs blood pressure remained
      uncontrolled. Selective left renal arteriography demonstrated two consecutive
      high-grade stenotic lesions with post-stenotic aneurysmal dilatation treated
      successfully with balloon dilatation. During the ensuing 2 year follow up
      complete normalization of blood pressure was observed. This case illustrates that
      endovascular therapy may be beneficial and should be considered a reasonable
      first option in these patients. However vascular involvement in NF may be
      progressive and therefore always requires continuing follow up.

PMID- 17451149
TI  - Analbuminemia presenting with severe hypercholesterolemia: a risk for
      atherosclerosis?

PMID- 17451150
TI  - [Depression in children and adolescents: prevalence, diagnosis, etiology, gender
      differences and therapeutic approaches].
AB  - Prevalence rates of the different forms of depression (depressive mood,
      depressive syndromes and Major Depression) have increased during recent years.
      Similarily, gender differences have augmented. Stress, dysfunctional coping
      styles, a negative body image, and an insecure attachment style have been
      identified as factors contributing to the etiology of depression. Different
      therapeutic approaches were presented with psychonanalytic treatment being the
      most comprehensive.

PMID- 17451151
TI  - [Emotional deprivation and narcissistic regulation--development and treatment of
      depressive crises in children and adolescents].
AB  - This paper outlines developmental and treatment issues of depression in childhood
      and adolescence. Impairment of parental empathy based on emotional disturbances
      of a parent leads to adaptive reactions as the child is confronted with threats
      of loss and separation. Hereditary vulnerability as well as insecure attachment
      patterns and the effects of explicit trauma must be viewed as further
      facilitating factors. Anxiety in children and--with the advent of adolescence-
      suicidal behaviour are described as important tools for narcissistic regulation
      and reconciliation and for mobilising help. Accordingly the last section of the
      paper is dedicated to therapeutic approaches to adolescent despair, depression,
      risk taking and suicidal behaviour. Guiding suicidal adolescents out of their
      crises can be a tightrope walk between attempts to limit life threatening acting
      out behaviours, leniency toward the patients' grandiosity along with sensitivity
      for narcissistic injuries and the building of a viable narcissistic transference.

PMID- 17451152
TI  - [Medical treatment of depression in children and adolescents].
AB  - Pharmacological treatment of depression in minors is contested after some
      published warnings about suicide related behaviour among youths treated with
      SSRI. This paper examines the last developments concerning antidepressant use in
      minors, prescrition patterns and evidence of antidepressants used in minors.
      Reviewing the guidelines and practise parameters, metaanalyses and the TADS-study
      a recommendation for an evidence based use in minors can only be given for
      Fluoxetine. Safety aspects should be taken into consideration during the
      treatment and patients should be kept in close contact to their therapists to
      observe suicidal related behaviour and adherence.

PMID- 17451153
TI  - [Postpartal depression: possible effects on early mother-child interaction and
      psychotherapeutical treatment approach].
AB  - The interaction between mother and child helds a central position in in- and
      outpatient treatment of postpartal depressive mothers. Infants are highly
      sensitive towards the emotional state of their mothers and other attachment
      figures. This sensivity is essential for the comprehension of the influence of a
      psychiatric illness of the mother on child development Postpartal depression as
      the most common psychiatric illness in young mothers takes a central part. The
      specific situation of young depressive mothers demands an adaptation of the
      therapeutic treatment. Different approaches towards the treatment of postpartal
      depression with respect to the mother-child interaction are elucidated.

PMID- 17451154
TI  - [Clinical treatment of a depressive adolescent].
AB  - This contribution presents the clinical treatment of a male adolescent suffering
      from depression. Structural aspects of the treatment were given. Treatment
      process is viewed as a multimodal, multiprofessional approach based on a systemic
      perspective. The uniqueness of the therapeutic process is outlined which makes
      highly professional and creative interventions necessary.

PMID- 17451155
TI  - [Psychoanalytic treatment of a drepressive girl which sufferend from loyality
      conflicts due to the divorce of her parents].
AB  - In this article, the long term psychoanalytic treatment of a depressive girl was
      presented, which suffered from loyality conflicts due to the divorce of her
      parents. The treatment lasted for 150 hours and was conducted over two years.
      Meetings with the parents were also included. The focus of this article is on the
      treatment of the girl.

PMID- 17451156
TI  - Purification and characterization of glucose 6-phosphate dehydrogenase from Lake
      Van fish (Chalcalburnus tarichii pallas, 1811) liver.
AB  - Glucose 6-phosphate dehydrogenase (D-glucose 6-phosphate: NADP+ oxidoreductase,
      EC 1.1.1.49; G6PD) was purified from Lake Van fish (Chalcalburnus tarichii
      pallas, 1811) liver, using a simple and rapid method, and some characteristics of
      the enzyme were investigated. The purification procedure was composed of two
      steps: homogenate preparation and 2', 5'-ADP Sepharose 4B affinity gel
      chromatography, which took 7-8 hours. Thanks to the two consecutive procedures,
      the enzyme, having specific activity of 38 EU/mg protein, was purified with a
      yield of 44.39% and 1310 fold. In order to control the enzyme purification SDS
      polyacrylamide gel electrophoresis (SDS-PAGE) was done. SDS polyacrylamide gel
      electrophoresis showed a single band for enzyme. Optimal pH, stable pH, optimal
      temperature, Km and, Vmax values for NADP+ and glucose 6-phosphate (G6P) were
      also determined for the enzyme. In addition, molecular weight and subunit
      molecular weights were found by sodium dodecyl sulfate polyacrilamide gel
      electrophoresis (SDS-PAGE) and gel filtration chromatography respectively.

PMID- 17451157
TI  - Early explosive force reduction associated with exercise-induced muscle damage.
AB  - This study was aimed to analyze the loss of muscle explosive force in the early
      phase of eccentric exercise-induced damage, and its possible relationships with
      muscle soreness and blood creatine kinase (CK) levels. Squat jump (SJ) and
      countermovement jump (CMJ) heights decreased in response to an eccentric exercise
      (120 eccentric actions of the knee extensors), with reductions that persisted at
      least for 24 h. The SJ/CMJ ratio was not significantly modified. Blood CK levels
      changed significantly over time and CK activity was significantly higher at 6 and
      at 24 h when compared to values obtained immediately after the eccentric
      exercise. Muscle soreness perceived at 6 h was slightly higher than that
      experienced just after finalizing the exercise and reached a clearly upper value
      at 24 h. A highly significant relationship between SJ and CMJ height loss was
      observed. CK activity at 24 h was significantly related to the SJ height loss at
      6 h and to both the SJ height loss and the CMJ height loss immediately after the
      exercise. In summary, eccentric exercise induced a reduction in the explosive
      force generating capacity that affected in a similar way the pure concentric jump
      (SJ) and the jump eliciting the stretch-shortening cycle (CMJ). Results obtained
      suggest that CK activity is a better predictor of explosive force reduction than
      soreness, at least when values close to the peak are used.

PMID- 17451158
TI  - Effect of vitamin E on diabetes-induced changes in small intestine and plasma
      antioxidant capacity in rat.
AB  - The present study was designed to evaluate the effect of Vitamin E (Vit. E) on
      diabetes-induced changes in small intestine, lipid peroxidation and plasma
      antioxidant capacity in rats. Twenty-four rats were divided into three groups
      (n=8), namely control, non-treated diabetic (NTD) and Vit. E-treated diabetic
      (VETD) groups. The VETD group received 300 mg of Vit. E daily in drinking water.
      After 6 weeks, the length and weight of small intestine, villus height, crypt
      depth and muscular layer thickness showed a significant increase in the NTD group
      compared to the control group. In the VETD group, these parameters did not show
      any significant difference compared to the control group. The level of
      malondialdehyde (MDA) in the red blood cells showed a significant increase in the
      NTD group, but not in the VETD group, compared to the control group. The plasma
      antioxidant capacity showed a significant increase in VETD compared to the NTD
      group. These findings indicate that Vit. E significantly improved small
      intestinal changes in diabetic rats and that these effects could be mediated at
      least in part by enhanced plasma antioxidant capacity and reduced lipid
      peroxidation.

PMID- 17451159
TI  - Patterns and variability in electrophoretic polypeptide profiles of human saliva
      in a healthy population.
AB  - Electrophoretic polypeptide profiles of normal human saliva differ markedly
      between different reports. Since both methodological variations and polymorphism
      may explain these differences, in this study we aimed to establish whether or not
      the salivary electrophoretic polypeptide profiles of subjects from a healthy
      population share discrete molecular features. To this end, parotid,
      submandibular/sublingual and whole salivas were collected separately from each of
      40 young and 34 elderly clinically healthy adults and processed for SDS
      polyacrylamide gel electrophoresis and Coomassie blue staining. Each type of
      glandular saliva displayed a different group of invariant (i.e. present in every
      subject) electrophoretic polypeptide bands while whole saliva showed a profile
      that reflected mostly the combined contribution of the major salivary glands.
      Some minor variant (i.e. absent in some subjects) bands were identified in each
      type of saliva. Regarding those interindividual variations, no age- or sex
      dependence was appreciated. Altogether, these results demonstrate the occurrence
      of distinctive electrophoretic polypeptide patterns, in addition to some minor
      variations, for each type of normal saliva, thus providing a background for
      further populational studies on salivary polypeptide profiles.

PMID- 17451160
TI  - Relationship between lipoprotein lipase and peroxisome proliferator-activated
      receptor-alpha expression in rat liver during development.
AB  - The present study was addressed to determine whether the high expression of
      peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in rat liver during
      the perinatal stage plays a role in the induction of liver lipoprotein lipase
      (LPL) expression and activity. Parallel increases in liver mRNA PPAR-alpha and
      LPL activity were found in newborn rats, and after a slight decline, values
      remained elevated until weaning. Anticipated weaning for 3 days caused a decline
      in those two variables as well as in the mRNA LPL level, and a similar change was
      also found in liver triacylglycerol concentration. Force-feeding with Intralipid
      in 10-day-old rats or animals kept fasted for 5 h showed high mRNA-PPARalpha and 
      LPL levels as well as LPL activity with low plasma insulin and high FFA levels,
      whereas glucose and a combination of glucose and Intralipid produced low mRNA
      PPARalpha and -LPL levels as well as LPL activity. Under these latter conditions,
      plasma insulin and FFA levels were high in those rats receiving the combination
      of glucose and Intralipid, whereas plasma FFA levels were low in those force-fed
      with glucose. It is proposed that the hormonal and nutritional induction of liver
      PPAR-alpha expression around birth and its maintained elevated level throughout
      suckling is responsible for the induction of liver LPL-expression and activity
      during suckling.

PMID- 17451161
TI  - Changes in erythrocyte morphology induced by imipramine and chlorpromazine.
AB  - Chlorpromazine (CPZ), a phenothiazine derivative, is a potent antipsychotic agent
      and imipramine (IP) is a widely used tricyclic antidepressant. The interaction
      between these molecules and erythrocyte membranes is of particular interest
      considering the role of these cells in the transport and release of these drugs
      at the central nervous system. In the present paper, we intend to study the
      effects of IP on erythrocyte membranes and to compare these effects with those of
      CPZ. Erythrocytes from adult Sprague-Dawley rats were incubated separately with
      different concentrations of IP or CPZ for lh at room temperature, fixed and
      stained by Giemsa. Changes in erythrocyte morphology were quantified by an image
      analysis system. The interaction of both drugs, CPZ and IP, with the erythrocyte
      membrane causes similar changes in cell shape. Increasing concentrations of both
      drugs induces the formation of stomatocytes, spherostomatocytes and spherocytes,
      because of an irreversible loss of area and volume, probably due to
      endovesiculation. Our results also show that the CPZ is more potent than IP.

PMID- 17451162
TI  - Comparative effects of melatonin and vitamin E in restoring aortic relaxation in
      pancreatectomized rats.
AB  - In a previous study we reported the efficacy of melatonin to restore the
      decreased relaxation response to acetylcholine (ACh) or to sodium nitroprusside
      (SNP) in aortic rings of rats turned hyperglycemic by subtotal pancreatectomy.
      The effect was amplified by pre-incubation in a high (44 mmol/l) glucose
      solution, a situation that resulted in oxidative stress. We hereby compare the
      effect of another antioxidant, vitamin E, with that of melatonin on ACh response
      in intact aortic rings or on SNP response in endothelium-denuded aortic rings
      obtained from pancreatectomized or sham-operated rats. Dose-response curves to
      ACh or SNP were performed in the presence or absence of melatonin or vitamin E
      (10-5 mol/1) in 10 or 44 mmol/1 glucose medium. Melatonin was more effective than
      vitamin E in restoring ACh- or SNP-induced relaxation of aortic rings in a high
      glucose medium. The differences between the two antioxidants may rely on the
      ability of melatonin to diffuse readily into intracellular compartments.

PMID- 17451163
TI  - Antioxidant levels in tissues of young and adult camels (Camelus dromedarius).
AB  - In this study, we measured the concentration of some antioxidant substances in
      erythrocytes hemolysate, liver, kidney and brain in young and adult camels. It
      has been found that the activity of the antioxidant enzymes glutathione
      peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD) and the
      concentration of glutathione, ascorbic acid and alpha-tocopherol are high in both
      young and adult camels. GSH-Px and CAT activities were higher in adult camels
      than in the young whereas no significant difference in the activity of SOD
      between young and adult camels was noticed. Glutathione was present in all
      tissues studied. Ascorbic acid was found to have significantly higher values in
      young camels. From this study it could be concluded that, as in other mammals,
      camel tissues contain a powerful antioxidant system. The liver has the highest
      contents of antioxidants and antioxidant enzymes indicating that it plays an
      important role in pro-oxidants detoxification. Age has a variable effect on the
      antioxidant system in camels.

PMID- 17451164
TI  - Protein-small molecule interactions in neocarzinostatin, the prototypical
      enediyne chromoprotein antibiotic.
AB  - The enediyne chromoproteins are a class of potent antitumour antibiotics
      comprising a 1:1 complex of a protein and a noncovalently bound chromophore. The
      protein is required to protect and transport the highly labile chromophore, which
      acts as the cytotoxic component by reacting with DNA leading to strand cleavage.
      A derivative of the best-studied member of this class, neocarzinostatin (NCS), is
      currently in use as a chemotherapeutic in Japan. The application of the
      chromoproteins as therapeutics along with their unique mode of action has
      prompted widespread interest in this area. Notable developments include the
      discovery of non-natural ligands for the apoproteins and the observation that
      multiple binding modes are available for these ligands in the binding site.
      Mutation studies on the apoproteins have revealed much about their stability and
      variability, and the application of an in vitro evolution method has conferred
      new binding specificity for unrelated ligands. These investigations hold great
      promise for the application of the apoproteins for drug-delivery, transport and
      stabilisation systems.

PMID- 17451166
TI  - Spectral near-infrared fluorescence imaging of curved surfaces using projection
      reconstruction algorithms.
AB  - In vivo spectral fluorescence imaging has made it possible to non-invasively
      visualize superficial curved structures as well as structures deep to the skin.
      However, the defocus created by blurring has been an obstacle to creating
      anatomically interpretable surface images. Herein we present a methodology to
      correct for blurring induced by curved structures during spectral fluorescence
      imaging using signal intensity projection algorithms. In a phantom and an animal
      model in which the lymphatic system was visualized after the interstitial
      injection of quantum dots with emission spectra in the near-infrared (NIR) range,
      the planes of focus were sequentially adjusted to obtain a z-stack of images
      which contains images acquired from multiple focal points. Maximum, minimum,
      median and average intensity projections were applied to the resulting images.
      Using the phantom, the minimum and the median intensity projection images
      demonstrated improved deblurring whereas during in vivo imaging the median
      intensity projection images more clearly visualized important structures than did
      the other projection techniques. Image stacking with subsequent application of
      appropriate projection techniques provides a simple method for deblurring in vivo
      optical images obtained from curved surfaces, thus improving their anatomic
      resolution.

PMID- 17451167
TI  - Measurement of nonlinear pO2 decay in mouse lungs using 3He-MRI.
AB  - Spatial and temporal variations in oxygen partial pressure (pO(2)) during breath
      hold can be exploited to obtain important regional parameters of lung function.
      In the course of apnea, the oxygen concentration is known to decay exponentially.
      Therefore, the initial pO(2) (p(0)) can be used to represent local ventilation,
      and the oxygen depletion time constant can characterize perfusion. The protocol,
      based on a nonlinear model of pO(2) decay, was validated in six healthy mice.
      Parametric maps of p(0) and oxygen depletion time constant were obtained for pure
      (3)He and (3)He/air mixture. The mean measured values of p(0) were 77 +/- 9 mbar
      for the pure (3)He insufflation and 107 +/- 5 mbar for (3)He/air mixture, in
      agreement with the predefined p(0) values: 75 +/- 15 mbar and 123 +/- 15 mbar,
      respectively. The mean measured oxygen depletion time constants were 6.5 +/- 0.2
      s for pure (3)He and 7.1 +/- 0.8 s for the (3)He/air mixture, in agreement with
      physiology.

PMID- 17451168
TI  - 4D cardiac MRI in the mouse.
AB  - With the introduction of mouse models for the study of cardiac morphogenesis,
      there arises a need for new imaging protocols that can capture both morphological
      and functional information. High-resolution 2D cardiac cine MRI has often been
      used to quantify left and right ventricular function. In this study we propose a
      3D isotropic cardiac cine MRI protocol with a voxel size of 200 microm(3) as a
      means of studying cardiac multi-chamber morphology and function. A black blood
      sequence was used to enhance blood myocardium contrast. Manual segmentation of
      the ventricles was used to measure ventricular volumes at end diastole and end
      systole. This method is demonstrated on an Irx4-deficient mouse model. We have
      been able to identify the volumes of both ventricles dynamically and to show
      differences in ejection fraction in the mutant. We have also identified an
      abnormality of the papillary muscle in the mutant that had been missed in
      previous phenotyping with ultrasound and histology.

PMID- 17451169
TI  - MR technology for biological studies in mice.
AB  - Mouse models are crucial for the study of genetic factors and processes that
      influence human disease. In addition to tools for measuring genetic expression
      and establishing genotype, tools to accurately and comparatively assess mouse
      phenotype are essential in order to characterize pathology and make comparisons
      with human disease. MRI provides a powerful means of evaluating various
      anatomical and functional changes and hence is growing in popularity as a
      phenotypic readout for biomedical research studies. To accommodate the large
      numbers of mice needed in most biological studies, mouse MRI must offer high
      throughput image acquisition and efficient image analysis. This article reviews
      the technology of multiple-mouse MRI, a method that images multiple mice or
      specimens simultaneously as a means of enabling high-throughput studies. Aspects
      of image acquisition and computational analysis in multiple-mouse studies are
      also described.

PMID- 17451170
TI  - MRI in mouse developmental biology.
AB  - Mice are used in many studies to determine the role of genetic and molecular
      factors in mammalian development and human congenital diseases. MRI has emerged
      as a major method for analyzing mutant and transgenic phenotypes in developing
      mice, at both embryonic and neonatal stages. Progress in this area is reviewed,
      with emphasis on the use of MRI to analyze cardiovascular and neural development
      in mice. Comparisons are made with other imaging technologies, including optical
      and ultrasound imaging, discussing the potential strengths and weaknesses of MRI
      and identifying the future challenges for MRI in mouse developmental biology.

PMID- 17451171
TI  - Magnetic resonance imaging and spectroscopy of transgenic models of cancer.
AB  - The complexity of cancer, where a single genetic alteration can have multiple
      functional effects, makes it a fascinating but humbling disease to study, and the
      necessity of investigating it in its entirety is more imperative than ever
      before. Advances in transgene technology have made it possible to create cancer
      cells, or mice with specific genetic alterations, and the application of an array
      of both functional and molecular non-invasive MR methods to these transgenic
      cancer cells and mice to characterize their phenotypic traits is revolutionizing
      our understanding of cancer. With the establishment of multi-modality molecular
      imaging centers within barrier or pathogen-free facilities, multi-parametric and
      multi-modality imaging of transgenic mouse models of human cancer are becoming
      increasingly prevalent. In this review, we outline some of the methods currently
      available for generating transgenic mice and cancer cell lines. We also present
      examples of the application of MR methods to transgenic models that are providing
      novel insights into the molecular and functional characteristics of cancer and
      are leading to an era of "non-invasive phenotyping" of the effects of specific
      molecular alterations in cancer.

PMID- 17451173
TI  - MRI monitoring of focal cerebral ischemia in peroxisome proliferator-activated
      receptor (PPAR)-deficient mice.
AB  - Peroxisome proliferator-activated receptors (PPARs) are a potential target for
      neuroprotection in focal ischemic stroke. These nuclear receptors have major
      effects in lipid metabolism, but they are also involved in inflammatory
      processes. Three PPAR isotypes have been identified: alpha, beta (or delta) and
      gamma. The development of PPAR transgenic mice offers a promising tool for
      prospective therapeutic studies. This study used MRI to assess the role of
      PPARalpha and PPARbeta in the development of stroke. Permanent middle cerebral
      artery occlusion induced focal ischemia in wild-type, PPARalpha-null mice and
      PPARbeta-null mice. T(2)-weighted MRI was performed with a 7 T MRI scan on day 0,
      1, 3, 7 and 14 to monitor lesion growth in the various genotypes. General Linear
      Model statistical analysis found a significant difference in lesion volume
      between wild-type and PPAR-null mice for both alpha and beta isotypes. These data
      validate high-resolution MRI for monitoring cerebral ischemic lesions, and
      confirm the neuroprotective role of PPARalpha and PPARbeta in the brain.

PMID- 17451172
TI  - Contrast-enhanced MRI of right ventricular abnormalities in Cx43 mutant mouse
      embryos.
AB  - Imaging of the mammalian cardiac right ventricle (RV) is particularly
      challenging, especially when a two-dimensional method such as conventional
      histology is used to evaluate the morphology of this asymmetric, crescent-shaped
      chamber. MRI may improve the characterization of mutants with RV phenotypes by
      allowing analysis of the samples in any plane and by facilitating three
      dimensional image reconstruction. MRI was used to examine the conditional
      knockout Cx43-PCKO mouse line known to have RV malformations. To help delineate
      the cardiovascular system and facilitate identification of the right ventricular
      outflow tract (RVOT), embryonic day (E) 17.5 embryos were perfusion fixed through
      the umbilical vein followed by a gadolinium-based contrast agent mixed in 7%
      gelatin. Micro-MRI experiments were performed at 7 T and followed by paraffin
      embedding of specimens, histological sectioning and hematoxylin and eosin (H&E)
      staining. Imaging of up to four embryos simultaneously allowed for higher
      throughput than traditional individual imaging techniques, while intravascular
      contrast afforded excellent signal-to-noise characteristics. All control embryos
      (n = 4) and heterozygous Cx43 knockout embryos (n = 4) had normal-appearing right
      ventricular outflow tract contours by MRI. Obvious abnormalities in the RVOT,
      including abnormal bulging and infiltration of contrast into the wall of the RV,
      were seen in three out of four Cx43-PCKO mutants with MRI. Furthermore, three
      dimensional reconstruction of MR images with orthogonal projections as well as
      maximum-intensity projection allowed for visualization of the relationship of
      infundibular bulging segments to the pulmonary trunk in Cx43-PCKO mutant hearts.
      The addition of MRI to standard histology in the characterization of RV
      malformations in mutant mouse embryos aids in the assessment and understanding of
      morphologic abnormalities. Flexibility in the viewing of MR images, which can be
      retrospectively sectioned in any desired orientation, is particularly useful in
      the investigation of the RV, an asymmetric chamber that is difficult to analyze
      with two-dimensional techniques.

PMID- 17451174
TI  - Non-invasive MRI of mouse models of atherosclerosis.
AB  - Early detection and characterization of atherosclerotic lesions susceptible to
      sudden rupture and thrombosis may decrease morbidity and mortality. Plaque
      development has been extensively studied using MRI in animal models of rapidly
      progressing atherosclerosis. These transgenic mice develop atherosclerotic
      plaques in the aortic root by 10 weeks of age and throughout the vasculature
      thereafter. Transplantation of lesion-containing segments of the thoracic aorta
      into wild-type mice results in nearly total reversal of atherosclerosis, making
      it possible to study both progression and regression of plaques in this model.
      MRI permits the non-invasive accurate assessment of atherosclerotic plaque burden
      and the differentiation between the lipid and fibrous content of individual
      plaques, thus providing a non-invasive approach to serially monitor the evolution
      of individual plaques in the mouse models. Emergence of novel contrast agents
      that target a diverse set of molecules within the plaque are now helping to
      elucidate the changes at the cellular and molecular levels during plaque
      progression and regression.

PMID- 17451175
TI  - In vivo mouse imaging and spectroscopy in drug discovery.
AB  - Imaging modalities such as micro-computed tomography (micro-CT), micro-positron
      emission tomography (micro-PET), high-resolution MRI, optical imaging, and high
      resolution ultrasound have become invaluable tools in preclinical pharmaceutical
      research. They can be used to non-invasively investigate, in vivo, rodent biology
      and metabolism, disease models, and pharmacokinetics and pharmacodynamics of
      drugs. The advantages and limitations of each approach usually determine its
      application, and therefore a small-rodent imaging laboratory in a pharmaceutical
      environment should ideally provide access to several techniques. In this paper we
      aim to illustrate how these techniques may be used to obtain meaningful
      information for the phenotyping of transgenic mice and for the analysis of
      compounds in murine models of disease.

PMID- 17451176
TI  - Neurodevelopment of C57B/L6 mouse brain assessed by in vivo diffusion tensor
      imaging.
AB  - Heterogeneous spatiotemporal patterns of C57B/L6 murine brain maturation during
      the first 7 weeks after birth (i.e. P15 to P45) were assessed in vivo by
      diffusion tensor imaging (DTI) at 9.4 T. Maps of apparent diffusion coefficient
      (ADC) and fractional anisotropy (FA) were used to assess developmental changes.
      Because directionally encoded color (DEC) maps provide an efficient and
      straightforward way to visualize anisotropy direction, they were used to
      highlight the orientation-dominant anisotropic tissues. In the corpus callosum,
      the increases in FA (approximately 0.4 to approximately 0.6 from P15 to P45) were
      primarily dominant in the medial-lateral direction, whereas the ADC decreased
      slightly (approximately 0.8 x 10(-3) to approximately 0.5 x 10(-3) mm(2)/s from
      P15 to P45). Similar increases in FA (approximately 0.3 to approximately 0.4 from
      P15 to P45) and decreases in ADC (approximately 0.8 x 10(-3) to approximately 0.5
      x 10(-3) mm(2)/s from P15 to P45) were found in the cingulate, but these
      anisotropic changes were dominant in the anterior-posterior direction. In the
      caudate putamen, there were significant FA increases (approximately 0.1 to
      approximately 0.2 from P15 to P45) dominant in the dorsal-ventral and anterior
      posterior directions, whereas the ADC increased rapidly early in development
      (approximately 0.3 x 10(-3) to approximately 0.7 x 10(-3) mm(2)/s from P15 to
      P17). There were no significant changes in tissue anisotropy in the somatosensory
      regions (whisker, forelimb), but the ADC decreased slightly (approximately 0.7 x
      10(-3) to approximately 0.5 x 10(-3) mm(2)/s from P15 to P45). Although the major
      differences in DEC values were mainly observed in white matter pathways, other
      cortical and subcortical regions showed some potential morphological changes that
      were consistent with classical histological findings. In summary, these results
      show that high-resolution DTI at high magnetic fields allows detection and
      quantification of brain structures throughout normal development in C57B/L6 mice
      in vivo.

PMID- 17451177
TI  - Postmortem delay does not change regional diffusion anisotropy characteristics in
      mouse spinal cord white matter.
AB  - It has been demonstrated previously that water diffusion anisotropy in vivo is
      equivalent to that observed ex vivo after perfusion fixation in the mouse brain.
      This finding supports the practice of ex vivo diffusion tensor imaging (DTI)
      measurement on perfusion-fixed tissues. However, the validity of extrapolating ex
      vivo DTI measurements from immersion-fixed autopsy specimens to the in vivo state
      is questionable because of variable postmortem delays often encountered before
      fixation. In this study, we investigated the effect of postmortem delay on the
      water diffusion anisotropy of ventrolateral spinal cord white matter from mice.
      Mouse spinal cords, each from the same animal, were examined using DTI in vivo,
      in situ after death before fixation, and ex vivo immersion fixed 10 h after
      death. Our results suggest that diffusion anisotropy in mouse spinal cord is
      preserved up to 10 h after death. Regional characteristics of diffusion
      anisotropy in mouse spinal cord white matter are equivalent in vivo, in situ
      after death (up to 10 h before fixation), and ex vivo 15 weeks after immersion
      fixation.

PMID- 17451178
TI  - Quantitative MRI reveals aging-associated T2 changes in mouse models of
      Alzheimer's disease.
AB  - In this study, we used MRI to analyze quantitative parametric maps of transverse
      (T(2)) relaxation times in a longitudinal study of transgenic mice expressing
      mutant forms of amyloid precursor protein (APP), presenilin (PS1), or both
      (PS/APP), modeling aspects of Alzheimer's disease (AD). The main goal was to
      characterize the effects of progressive beta-amyloid accumulation and deposition
      on the biophysical environment of water and to investigate if these measurements
      would provide early indirect evidence of AD pathological changes in the brains of
      these mice. Our results demonstrate that at an early age before beta-amyloid
      deposition, only PS/APP mice show a reduced T(2) in the hippocampus and cortex
      compared with wild-type non-transgenic (NTg) controls, whereas a statistically
      significant within-group aging-associated decrease in T(2) values is seen in the
      cortex and hippocampus of all three transgenic genotypes (APP, PS/APP, and PS)
      but not in the NTg controls. In addition, for animals older than 12 months, we
      confirmed our previous report that only the two genotypes that form amyloid
      plaques (APP and PS/APP) have significantly reduced T(2) values compared with NTg
      controls. Thus, T(2) changes in these AD models can precede amyloid deposition or
      even occur in AD models that do not deposit beta-amyloid (PS mice), but are
      intensified in the presence of amyloid deposition.

PMID- 17451179
TI  - Mouse MRI using phased-array coils.
AB  - The advantages of array coil imaging in human whole-body MR systems are well
      known and have gained relevance in many applications and MR techniques. In the
      field of small-animal studies, this concept has become increasingly important. In
      this work, three different phased-array coils for performing MRI on mice are
      presented. For imaging at 300 MHz, a four-channel receive-only phased-array coil
      is introduced. One two-channel and a four-channel transmit/receive setup
      operating at 750 MHz show the feasibility of array coil imaging at 17.6 T. All of
      these coils show excellent performance and deliver high-quality MR images of
      mice.

PMID- 17451180
TI  - Radio frequency coil technology for small-animal MRI.
AB  - A review of the theory, technology, and use of radio frequency (RF) coils for
      small-animal MRI is presented. It includes a brief overview of MR signal-to-noise
      (S/N) analysis and discussions of the various coils commonly used in small-animal
      MR: surface coils, linear volume coils, birdcages, and their derivatives. The
      scope is limited to mid-range coils, i.e. coils where the product (fd) of the
      frequency f and the coil diameter d is in the range 2-30 MHz-m. Common
      applications include mouse brain and body coils from 125 to 750 MHz, rat body
      coils up to 500 MHz, and small surface coils at all fields. In this regime, all
      the sources of loss (coil, capacitor, sample, shield, and transmission lines) are
      important. All such losses may be accurately captured in some modern full-wave 3D
      electromagnetics software, and new simulation results are presented for a
      selection of surface coils using Microwave Studio 2006 by Computer Simulation
      Technology, showing the dramatic importance of the "lift-off effect". Standard
      linear circuit simulators have been shown to be useful in optimization of complex
      coil tuning and matching circuits. There appears to be considerable potential for
      trading S/N for speed using phased arrays, especially for a larger field of view.
      Circuit simulators are shown to be useful for optimal mismatching of ultra-low
      noise preamps based on the enhancement-mode pseudomorphic high-electron-mobility
      transistor for optimal coil decoupling in phased arrays. Cryogenically cooled RF
      coils are shown to offer considerable opportunity for future gains in S/N in
      smaller samples.

PMID- 17451181
TI  - Developing MR reporter genes: promises and pitfalls.
AB  - MR reporter genes have the potential to monitor transgene expression non
      invasively in real time at high resolution. These genes can be applied to
      interrogate the efficacy of gene therapy, to assess cellular differentiation,
      cell trafficking, and specific metabolic activity, and also assess changes in the
      microenvironment. Efforts toward the development of MR reporter genes have been
      made for at least a decade, but, despite these efforts, the field is still in its
      early developmental stage. This reflects the fact that there are potential
      pitfalls, caused by the low sensitivity of detection, the need for substrates
      with their associated undesirable pharmacokinetics, and/or the difficult and, in
      some cases, delayed interpretation of signal changes. Nevertheless, significant
      progress has been made during the last few years. Whereas enzyme-based reporters
      were initially applied to NMR spectroscopic monitoring of changes in phosphor and
      fluorine metabolism, MRI-based approaches are now emerging that rely on: (1)
      enzyme-based cleavage of functional groups that block water (proton) exchange or
      protein binding of MR contrast agents; (2) expression of surface receptors that
      enable binding of specific MR contrast agents; (3) expression of para- and anti
      ferromagnetic (metallo)proteins involved with iron metabolism, such as
      tyrosinase, transferrin receptor, and ferritin. After an introduction to the
      basic principles of designing promoters, expression vectors, and cloning of
      transgenes, a fresh look is provided on the use of reporter genes for optical
      (including bioluminescent) and nuclear imaging, with which MR reporter genes
      compete. Although progress in the use of MR reporter genes has been slow, newer
      strategies that use metalloproteins or alternative contrast mechanisms, with no
      need for substrates, promise rapid growth potential for this field.

PMID- 17451182
TI  - MR in mouse models of cardiac disease.
AB  - Transgenic and knockout mice can be used to study the genes and basic mechanisms
      involved in heart disease, and have therefore assumed a central role in modern
      cardiac research. MRI and MRS techniques have recently been developed for mice
      that enable the quantitative or semi-quantitative in vivo assessment of cardiac
      anatomy, function, perfusion, infarction, Ca(2+) influx, and metabolism. With
      these techniques, the normal mouse heart has been shown to be well suited as a
      model of human cardiac disease. The roles of individual genes in normal cardiac
      physiology have recently been studied by MR, including the role of neuronal
      nitric oxide synthase in beta-adrenergic stimulation, the roles of the inducible
      nitric oxide synthase and myoglobin in function, dilation, and energetics, and
      the role of cardiac troponin I in contractility. Furthermore, with a mouse model
      of myocardial infarction, the roles of the angiotensin II type 2 receptor,
      xanthine oxidase inhibitors, blood coagulation factor XIII, and inducible nitric
      oxide synthase in post-infarct function and remodeling have been further
      elucidated. Non-invasive in vivo MRI and MRS in mice provide a unique and
      powerful means for phenotyping genetically engineered mice and can improve our
      understanding of the roles of specific genes and proteins in cardiac physiology
      and pathophysiology.

PMID- 17451183
TI  - Application of MRS to mouse models of neurodegenerative illness.
AB  - The rapid development of transgenic mouse models of neurodegenerative diseases,
      in parallel with the rapidly expanding growth of MR techniques for assessing in
      vivo, non-invasive, neurochemistry, offers the potential to develop novel markers
      of disease progression and therapy. In this review we discuss the interpretation
      and utility of MRS for the study of these transgenic mouse and rodent models of
      neurodegenerative diseases such as Alzheimer's (AD), Huntington's (HD) and
      Parkinson's disease (PD). MRS studies can provide a wealth of information on
      various facets of in vivo neurochemistry, including neuronal health, gliosis,
      osmoregulation, energy metabolism, neuronal-glial cycling, and molecular
      synthesis rates. These data provide information on the etiology, natural history
      and therapy of these diseases. Mouse models enable longitudinal studies with
      useful time frames for evaluation of neuroprotection and therapeutic
      interventions using many of the potential MRS markers. In addition, the ability
      to manipulate the genome in these models allows better mechanistic understanding
      of the roles of the observable neurochemicals, such as N-acetylaspartate, in the
      brain. The argument is made that use of MRS, combined with correlative histology
      and other MRI techniques, will enable objective markers with which potential
      therapies can be followed in a quantitative fashion.

PMID- 17451184
TI  - MRI of mouse models of neurological disorders.
AB  - MRI has contributed to significant advances in the understanding of neurological
      diseases in humans. It has also been used to evaluate the spectrum of mouse
      models spanning from developmental abnormalities during embryogenesis, evaluation
      of transgenic and knockout models, through various neurological diseases such as
      stroke, tumors, degenerative and inflammatory diseases. The MRI techniques used
      clinically are technically more challenging in the mouse because of the size of
      the brain; however, mouse imaging provides researchers with the ability to
      explore cellular and molecular imaging that one day may translate into clinical
      practice. This article presents an overview of the use of MRI in mouse models of
      a variety of neurological disorders and a brief review of cellular imaging using
      magnetically tagged cells in the mouse central nervous system.

PMID- 17451186
TI  - The effects of intramolecular H-bond formation on the stability constant and
      water exchange rate of the Gd(III)-diethylenetriamine-N'-(3-amino-1,1
      propylenephosphonic)-N, N,N'',N''-tetraacetate complex.
AB  - The binding interaction of metal chelates to biological macromolecules, though
      driven by properly devoted recognition synthons, may cause dramatic changes in
      some property associated with the coordination cage such as the thermodynamic
      stability or the exchange rate of the metal coordinated water. Such changes are
      due to electrostatic and H-bonding interactions involving atoms of the
      coordination cage and atoms of the biological molecule at the binding site. To
      mimic this type of H-bonding interactions, lanthanide(III) complexes with a DTPA
      monophosphonate ligand bearing a propylamino moiety (H6NP-DTPA) were synthesized.
      Their thermodynamic stabilities and the exchange lifetime of the coordinated
      water molecule (for the Gd-complex) were compared with those of the analog
      complexes with DTPA and the parent DTPA-monophosphonate derivative (H6P-DTPA). It
      was found that the intramolecular H-bond between the epsilon-amino group and the
      phosphonate moiety in NP-DTPA complexes causes displacements of electric charges
      in their coordination cage that are markedly pH dependent. In turn, this affects
      the characteristic properties of the coordination cage. In particular it results
      in a marked elongation of the exchange lifetime of the coordinated water
      molecule.

PMID- 17451187
TI  - Oxidative stress and DNA hypermethylation status in renal cell carcinoma arising
      in patients on dialysis.
AB  - Renal cell carcinoma (RCC) is more frequently observed in patients on dialysis
      than in patients with normal renal function. However, the mechanism underlying
      carcinogenesis in RCC patients on dialysis is still unclear. We hypothesized that
      oxidative stress affects patients on dialysis and generates new neoplasms, and
      therefore analysed the correlation between the influences of various markers of
      oxidative stress and carcinogenesis in those patients. We evaluated the
      immunohistochemical expression of oxidative stress markers, such as iNOS, 8-OHdG,
      and COX-2 in 42 cases on dialysis and 51 cases with normal renal function as a
      control. The methylation status of p16INK4a, p14ARF, VHL, and RASSF1A was
      analysed together with clinicopathological factors. Histologically, the papillary
      type was observed more frequently in dialysis RCC than in sporadic RCC.
      Immunohistochemically, overexpression of iNOS (p < 0.0001) and COX-2 (p = 0.0002)
      was more frequently observed in dialysis RCC. Furthermore, the 8-OHdG labelling
      index was significantly higher in dialysis RCC than in sporadic RCC.
      Hypermethylation of p16INK4a was more frequently found in dialysis RCC (p <
      0.05). However, no significant correlations between oxidative stress markers and
      DNA hypermethylation status were observed. The overexpression of iNOS, COX-2, and
      8-OHdG in dialysis RCC suggests that patients on dialysis are affected by
      oxidative stress and that this effect plays an important role in the genesis of
      dialysis RCC.

PMID- 17451188
TI  - Fetus in fetu--from prenatal ultrasound and MRI diagnosis to postnatal
      confirmation.
AB  - We report a case of fetus in fetu presented as a complex intra-abdominal
      heterogeneous cystic lesion during ultrasound examination of the fetus at 25
      weeks of gestation. Progressive growth of this mass was noted in the prenatal
      period. Fetal magnetic resonance imaging provided additional information to aid
      in the prenatal diagnosis. This allows proper counselling for the parents and
      helps to plan the postnatal management. Surgical excision was carried out in the
      early neonatal period and the diagnosis of fetus in fetu was confirmed.

PMID- 17451189
TI  - How to determine the number of inner-sphere water molecules in Lanthanide(III)
      complexes by 17O NMR spectroscopy. A technical note.
AB  - Lanthanide(III) complexes of polyaminocarboxylates are widely used in MRI as
      contrast agents. The paramagnetic properties of the metal ion contribute to the
      increase of (1)H relaxation rates, while the chelate offers a stable binding with
      the metal. The number of water molecules, coordinated directly to the Ln(III)
      ion, is very important for the relaxivity and, thus, the efficacy of these
      contrast agents. Here, we describe convenient methods to determine this parameter
      by measurement of Ln(III)-induced shifts of the water (17)O NMR resonance.

PMID- 17451190
TI  - Application of QF-PCR for the prenatal assessment of discordant monozygotic twins
      for fetal sex.
AB  - OBJECTIVE: To establish the utility of quantitative fluorescent polymerase chain
      reaction (QF-PCR) in order to determine the zygosity of multiple pregnancies, as
      well as to define the origin of the most frequent aneuploidies in amniotic fluid
      samples. METHODS: We describe the case of a monochorionic (MC) diamniotic (DA)
      pregnancy with phenotypically discordant twins (nuchal cystic hygroma and non
      immune hydrops in twin A and no anomalies in twin B). QF-PCR was performed for
      rapid prenatal diagnosis in uncultured amniocytes and subsequently in cultured
      cells. Polymorphic markers for chromosomes X, Y, 13, 18 and 21 were used for
      determination of zygosity as well as sex chromosome aneuploidy. RESULTS: Twin A
      showed a Turner Syndrome (TS) mosaicism pattern by QF-PCR in uncultured
      amniocytes. The monozygotic origin of the pregnancy was determined. Interphase
      fluorescence in situ hybridization (I-FISH) in this sample showed a mosaicism
      X0/XY (83/17%). Cytogenetic analysis revealed a 45,X0 karyotype in twin A and a
      46,XY karyotype in twin B. CONCLUSIONS: QF-PCR is a reliable tool for the
      determination of the zygosity independently of the chorionicity and the fetal sex
      in case of twin pregnancy. Testing both direct and cultured cells can provide
      useful results for genetic counselling in chromosomal mosaicisms.

PMID- 17451191
TI  - Prenatal detection of congenital bilateral cataract leading to the diagnosis of
      Nance-Horan syndrome in the extended family.
AB  - OBJECTIVES: To describe a family in which it was possible to perform prenatal
      diagnosis of Nance-Horan Syndrome (NHS). METHODS: The fetus was evaluated by 2nd
      trimester ultrasound. The family underwent genetic counseling and ophthalmologic
      evaluation. The NHS gene was sequenced. RESULTS: Ultrasound demonstrated fetal
      bilateral congenital cataract. Clinical evaluation revealed other family members
      with cataract, leading to the diagnosis of NHS in the family. Sequencing
      confirmed a frameshift mutation (3908del11bp) in the NHS gene. CONCLUSION:
      Evaluation of prenatally diagnosed congenital cataract should include a
      multidisciplinary approach, combining experience and input from sonographer,
      clinical geneticist, ophthalmologist, and molecular geneticist.

PMID- 17451192
TI  - Practical guidelines for the treatment of inflammatory bowel disease.
AB  - In recent years, great progress has been made regarding the treatment of
      inflammatory bowel disease (IBD), particularly in the field of biological
      therapies. Nevertheless, the ultimate treatment is not in sight. With the
      development of new medication, it has become clear that we need a new
      understanding of IBD. Therapy needs to fit the different subtypes of IBD; e.g.
      mild disease in comparison to severe chronic active disease or Crohn's disease
      with or without fistulation or stenosis. The following article gives a practical
      overview of actual treatments for IBD. The intention of this article is not to
      provide a complete review of all new scientific developments, but to give a
      practical guideline for therapy of IBD.

PMID- 17451193
TI  - New aspects in celiac disease.
AB  - Celiac disease (CD) is a common autoimmune disorder characterized by an immune
      response to ingested gluten and has a strong HLA association with HLA-DQ2 and HLA
      DQ8 molecules, but human HLA-DQ risk factors do not explain the entire genetic
      susceptibility to gluten intolerance. CD is caused by the lack of immune
      tolerance (oral tolerance) to wheat gluten. In this sense, the expression of
      soluble HLA-G in CD is of special interest because the molecule plays an
      important role in the induction of immune tolerance. The enhanced expression of
      soluble HLA-G found in CD may be part of a mechanism to restore the gluten
      intolerance. In this editorial, we review recent progress in understanding CD in
      relation to its prevalence, diagnosis and possible mechanisms of pathogenesis.

PMID- 17451194
TI  - (-)-Epigallocatechin-3-gallate inhibits growth of gastric cancer by reducing VEGF
      production and angiogenesis.
AB  - AIM: To investigate the effect of (-)-epigallocatechin-3-gallate (EGCG) on growth
      of gastric cancer and its possible mechanism. METHODS: Heterotopic tumors were
      induced by subcutaneously injection of SGC-7901 cells in nude mice. Tumor growth
      was measured by calipers in two dimensions. Tumor angiogenesis was determined
      with tumor microvessel density (MVD) by immunohistology. Vascular endothelial
      growth factor (VEGF) protein level and activation of signal transducer and
      activator of transcription 3 (Stat3) were examined by Western blotting. VEGF mRNA
      expression was determined by RT-PCR and VEGF release in tumor culture medium by
      ELISA. VEGF-induced cell proliferation was studied by MTT assay, cell migration
      by gelatin modified Boyden chamber (Transwell) and in vitro angiogenesis by
      endothelial tube formation in Matrigel. RESULTS: Intraperitoneal injection of
      EGCG inhibited the growth of gastric cancer by 60.4%. MVD in tumor tissues
      treated with EGCG was markedly reduced. EGCG treatment reduced VEGF protein level
      in vitro and in vivo. Secretion and mRNA expression of VEGF in tumor cells were
      also suppressed by EGCG in a dose-dependent manner. This inhibitory effect was
      associated with reduced activation of Stat3, but EGCG treatment did not change
      the total Stat3 expression. EGCG also inhibited VEGF-induced endothelial cell
      proliferation, migration and tube formation. CONCLUSION: EGCG inhibits the growth
      of gastric cancer by reducing VEGF production and angiogenesis, and is a
      promising candidate for anti-angiogenic treatment of gastric cancer.

PMID- 17451195
TI  - Downregulation of survivin by RNAi inhibits growth of human gastric carcinoma
      cells.
AB  - AIM: To investigate the inhibitory effect of a specific small survivin
      interfering RNA (siRNA) on cell proliferation and the expression of survivin in
      human gastric carcinoma cell line SGC-7901. METHODS: To knockdown survivin
      expression, a small interfering RNA targeting against survivin was synthesized
      and transfected into SGC-7901 cells with lipofectamine 2000. The downregulation
      of survivin expression at both mRNA and protein levels were detected by reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. Cell
      proliferation inhibition rates were determined by methyl thiazolyl tetrazolium
      (MTT) assay. The effect of survivin siRNA on cell cycle distribution and cell
      apoptosis was determined by flow cytometry (FCM). RESULTS: RNA interference could
      efficiently suppress the survivin expression in SGC-7901 cells. At 48 h after
      transfection, the expression inhibition rate was 44.52% at mRNA level detected by
      RT-PCR and 40.17% at protein level by Western blot analysis. Downregulation of
      survivin resulted in significant inhibition of tumor cell growth in vitro. The
      cell proliferation inhibition rates at 24, 48 and 72 h after survivin siRNA and
      non-silencing siRNA transfection, were 34.06%, 47.61% and 40.36%, respectively.
      The apoptosis rate was 3.56% and the number of cells was increased in G(0)/G(1)
      phase from 38.2% to 88.6%, and decreased in S and G(2)/M phase at 48 h after
      transfection. CONCLUSION: Downregulation of survivin results in significant
      inhibition of tumor growth in vitro. The inhibition of survivin expression can
      induce apoptosis of SGC-7901 cells. The use of survivin siRNA deserves further
      investigation as a novel approach to cancer therapy.

PMID- 17451196
TI  - Selective COX-2 inhibitor, NS-398, suppresses cellular proliferation in human
      hepatocellular carcinoma cell lines via cell cycle arrest.
AB  - AIM: To investigate the growth inhibitory mechanism of NS-398, a selective
      cyclooxygenase-2 (COX-2) inhibitor, in two hepatocellular carcinoma (HCC) cell
      lines (HepG2 and Huh7). METHODS: HepG2 and Huh7 cells were treated with NS-398.
      Its effects on cell viability, cell proliferation, cell cycles, and gene
      expression were respectively evaluated by water-soluble tetrazolium salt (WST-1)
      assay, 4'-6-diamidino-2-phenylindole (DAPI) staining, flow cytometer analysis,
      and Western blotting, with dimethyl sulfoxide (DMSO) as positive control.
      RESULTS: NS-398 showed dose- and time-dependent growth-inhibitory effects on the
      two cell lines. Proliferating cell nuclear antigen (PCNA) expressions in HepG2
      and Huh7 cells, particularly in Huh7 cells were inhibited in a time- and dose
      independent manner. NS-398 caused cell cycle arrest in the G1 phase with cell
      accumulation in the sub-G1 phase in HepG2 and Huh7 cell lines. No evidence of
      apoptosis was observed in two cell lines. CONCLUSION: NS-398 reduces cell
      proliferation by inducing cell cycle arrest in HepG2 and Huh7 cell lines, and COX
      2 inhibitors may have potent chemoprevention effects on human hepatocellular
      carcinoma.

PMID- 17451197
TI  - Assessment of hemodynamics in precancerous lesion of hepatocellular carcinoma:
      evaluation with MR perfusion.
AB  - AIM: To investigate the hemodynamic changes in a precancerous lesion model of
      hepatocellular carcinoma (HCC). METHODS: Hemodynamic changes in 18 Wistar rats
      were studied with non-invasive magnetic resonance (MR) perfusion. The changes
      induced by diethylnitrosamine (DEN) developed into liver nodular lesions due to
      hepatic cirrhosis during the progression of carcinogenesis. The MR perfusion data
      [positive enhancement integral (PEI)] were compared between the nodular lesions
      corresponding well with MR images and pathology and their surrounding hepatic
      parenchyma. RESULTS: A total of 46 nodules were located by MR imaging and
      autopsy, including 22 dysplastic nodules (DN), 9 regenerative nodules (RN), 10
      early HCCs and 5 overt HCCs. Among the 22 DNs, 6 were low-grade DN (LGDN) and 16
      were high-grade DN (HGDN). The average PEI of RN, DN, early and overt HCC was
      205.67 +/- 31.17, 161.94 +/- 20.74, 226.09 +/- 34.83, 491.86 +/- 44.61
      respectively, and their liver parenchyma nearby was 204.84 +/- 70.19. Comparison
      of the blood perfusion index between each RN and its surrounding hepatic
      parenchyma showed no statistically significant difference (P = 0.06). There were
      significant differences in DN (P = 0.02). During the late hepatic arterial phase,
      the perfusion curve in DN declined. DN had an iso-signal intensity at the early
      hepatic arterial phase and a low signal intensity at the portal venous phase. Of
      the 10 early HCCs, 4 demonstrated less blood perfusion and 6 displayed minimally
      increased blood flow compared to the surrounding parenchyma. Five HCCs showed
      significantly increased blood supply compared to the surrounding parenchyma (P =
      0.02). CONCLUSION: Non-invasive MR perfusion can detect changes in blood supply
      of precancerous lesions.

PMID- 17451198
TI  - Comethylation of p16 and MGMT genes in colorectal carcinoma: correlation with
      clinicopathological features and prognostic value.
AB  - AIM: To investigate the significance of p16 and O(6)-methylguanine-DNA
      methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on
      colorectal tumorigenesis and progression. METHODS: p16 and MGMT methylation
      status was examined on 47 tumor samples, and K-ras mutational status was examined
      on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS
      PCR) method was used. RESULTS: p16 and MGMT promoter methylation was found in 51%
      (24/47) and 43% (20/47) of CRCs, respectively, and the K-ras mutation was found
      in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly
      associated with lower aggressiveness of the disease within a two-year period of
      observation. Only 27% of patients with simultaneous p16 and MGMT methylation
      showed the detectable occurrence of metastasis and/or death, compared to 67% of
      patients without double methylation or with no methylation (3/11 vs 22/33, P <
      0.05, chi(2)-test). In addition, p16 and MGMT comethylation showed a trend toward
      an association with longer survival in patients with CRCs (35.5 +/- 6.0 mo vs
      23.1 +/- 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a
      two-year period was observed in 66% of patients carrying the K-ras mutation,
      compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P < 0.001,
      chi(2)-test). The presence of the K-ras mutation significantly correlated to
      shortened overall survival (20.0 +/- 1.9 mo vs 37.0 +/- 1.8 mo, P < 0.001, Log
      rank test). The comethylation of p16 and MGMT genes was significantly associated
      with lower aggressiveness of the disease even when K-ras mutations were included
      in the analysis as an independent variable. CONCLUSION: Our data suggest that
      comethylation of promoters of p16 and MGMT genes could have a prognostic value in
      patients with CRC. Specifically, concurrent methylation of both genes correlates
      with better prognosis.

PMID- 17451199
TI  - Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during
      interferon or combined interferon-ribavirin therapy.
AB  - AIM: To evaluate the implication of substitutions in the hepatitis C virus (HCV)
      non-structural 5A (NS5A) protein in the resistance of HCV during mono-interferon
      (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported
      to interact with the HCV RNA-dependent RNA polymerase, NS5B, as well as with many
      cellular proteins, the function of NS5A in the life cycle of HCV remains unclear.
      METHODS: HCV quasispecies were studied by cloning and sequencing of sequential
      isolates from patients infected by HCV genotype 1b. Patients were treated by IFN
      alpha2b for 3 mo followed by IFN-alpha2b alone or combined IFN-R therapy for 9
      additional months. Patients were categorized into two groups based on their
      response to the treatments: 7 with sustained virological response (SVR)
      (quasispecies = 150) and 3 non-responders (NR) to IFN-R (quasispecies = 106).
      RESULTS: Prior to treatment, SVR patients displayed a lower complexity of
      quasispecies than NR patients. Most patients had a decrease in the complexity of
      quasispecies during therapy. Analysis of amino acids substitutions showed that
      the degree of the complexity of the interferon sensitivity-determining region
      (ISDR) and the V3 domain of NS5A protein was able to discriminate the two groups
      of patients. Moreover, SVR patients displayed more variability in the NS5A region
      than NR patients. CONCLUSION: These results suggest that detailed molecular
      analysis of the NS5A region may be important for understanding its function in
      IFN response during HCV 1b infection.

PMID- 17451200
TI  - Epidemiology and transmission of hepatitis B and C viruses in Kazakhstan.
AB  - AIM: To investigate the epidemiology of hepatitis B virus (HBV) and hepatitis C
      virus (HCV) infection in the two major ethnic groups in Kazakhstan. METHODS: A
      cross-sectional prospective study of HBV and HCV seroprevalence was performed
      among individuals born in Kazakhstan with no history of chronic hepatitis or
      liver disease. RESULTS: There were 290 volunteers (140 Russians and 150 Kazakhs)
      aged 10 to 64 years, males accounted for 46%. Active HBV infection (HBsAg
      positive) was present in 3.8%, anti-HBc in 30%. The prevalence was similar in
      females and males (33% vs 25%) (P = 0.18). The prevalence of anti-HBc increased
      from 19% in 10-29 years old volunteers to 53% in 50-years and older volunteers.
      The prevalence of HBV infection was higher in married than in single adults (38%
      vs 26%, respectively) (P = 0.2) and more common in Kazakhs (35%) than in Russians
      (24%) (P = 0.07). HCV infection was present in 9 subjects (3.2%), 5 of them also
      were positive for anti-HBc in the absence of HBsAg. CONCLUSION: The frequency of
      active HBV infection (3.8%) coupled with a high prevalence of HBV exposure in
      those > 50 years of age increases with age, which suggests that horizontal
      transmission likely relates to the use of contaminated needles. The low
      prevalence of HCV infection suggests that HBV and HCV are acquired differently in
      this group of subjects.

PMID- 17451201
TI  - Antisense oligonucleotide targeting midkine suppresses in vivo angiogenesis.
AB  - AIM: To evaluate the effect of antisense oligonucleotide targeting midkine (MK
      AS) on angiogenesis in chick chorioallantoic membrane (CAM) and in situ human
      hepatocellular carcinoma (HCC). METHODS: An in situ human hepatocellular
      carcinoma (HCC) model and CAM assay were used in this experiment. The effect of
      MK-AS on angiogenesis was evaluated by cell proliferation assay and hematoxylin
      eosin (HE) staining. RESULTS: MK-AS significantly inhibited human umbilical vein
      endothelial cells (HUVEC) and in situ human HCC growth. At the same time, MK-AS
      suppressed the angiogenesis both in human hepatocellular carcinoma cell line
      (HEPG2)-induced CAM and in situ human HCC tissues. CONCLUSION: MK-AS is an
      effective antiangiogenesis agent in vivo.

PMID- 17451202
TI  - Tetrandrine stimulates the apoptosis of hepatic stellate cells and ameliorates
      development of fibrosis in a thioacetamide rat model.
AB  - AIM: To investigate the therapeutic effect of tetrandrine on liver fibrosis
      induced by thioacetamide in rats in vivo and in vitro. METHODS: In vitro study:
      we investigated the effect of tetrandrine on the apoptosis of rat hepatic
      stellate cells transformed by simian virus 40 (T-HSC/Cl-6), which retains the
      features of activated cells. In vivo study: hepatic fibrosis was induced in rats
      by thioacetamide. Tetrandrine was given orally to rats at doses of 5, 10 or 20
      mg/kg for 4 wk compared with intraperitoneal injection of interferon-r. RESULTS:
      In vitro study: 5, 10 or 25 microg/mL of tetrandrine-induced activation of
      caspase-3 in t-HSC/Cl-6 cells occurred dose-dependently. In vivo study:
      tetrandrine treatment as well as interferon-r significantly ameliorated the
      development of fibrosis as determined by lowered serum levels of aspartate
      aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil)
      and the levels of liver hydroxyproline (Hyp), hyaluronic acid (HA), laminin (LN)
      and also improved histological findings. The effects of tetrandrine at the
      concentration of 20 mg/kg were better than the other concentration groups.
      CONCLUSION: Tetrandrine promotes the apoptosis of activated HSCs in vitro.
      Tetrandrine administration can prevent liver fibrosis and liver damage induced by
      thioacetamide in rats in vivo, indicating that it might exert a direct effect on
      rat HSCs.

PMID- 17451203
TI  - Role of CARD15, DLG5 and OCTN genes polymorphisms in children with inflammatory
      bowel diseases.
AB  - AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5
      genes in disease predisposition and phenotypes in a large Italian cohort of
      pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred
      patients with Crohn's disease (CD), 186 ulcerative colitis (UC) patients, 434
      parents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of
      the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes,
      IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5
      gene were evaluated. Potential correlations with clinical sub-phenotypes were
      investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with
      CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P
      < 0.001). Homozygosis for both OCTN1/2 variants was more common in CD patients
      (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with
      an increased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No
      association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5
      variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while
      carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene
      gene interaction was found. In UC patients, the TC haplotype was more frequent
      (45.4%, P = 0.03), but no genotype/phenotype correlation was observed.
      CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated
      with pediatric onset of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a
      weak influence on CD phenotype.

PMID- 17451204
TI  - Molecularly defined adult-type hypolactasia among working age people with
      reference to milk consumption and gastrointestinal symptoms.
AB  - AIM: To study milk consumption and subjective milk-related symptoms in adults
      genotyped for adult-type hypolactasia. METHODS: A total of 1900 Finnish adults
      were genotyped for the C/T(-13910) variant of adult-type hypolactasia and filled
      in a structured questionnaire concerning milk consumption and gastrointestinal
      problems. RESULTS: The C/C(-13910) genotype of adult-type hypolactasia was
      present in 18% of the study population. The prevalence of the C/C(-13910)
      genotype was higher among subjects who were undergoing investigations because of
      abdominal symptoms (24%, P < 0.05). Those with the C/C(-13910) genotype drank
      less milk than subjects with either the C/T(-13910) or the T/T(-13910) genotype
      of lactase persistence (18% vs 38%; 18% vs 36%, P < 0.01). Subjects with the C/C(
      13910) genotype had experienced more gastrointestinal symptoms (84%) during the
      preceding three-month period than those with the C/T(-13910) (79%, P < 0.05) or
      the T/T(-13910) genotype (78 %, P < 0.05). Only 9% (29/338) of the subjects with
      the C/C(-13910) genotype consumed milk and reported no symptoms from it.
      CONCLUSION: Gastrointestinal symptoms are more common among adults with the C/C(
      13910) genotype of adult-type hypolactasia than in those with genotypes of
      lactase persistence.

PMID- 17451205
TI  - Clinical investigation of 41 patients with ischemic colitis accompanied by ulcer.
AB  - AIM: To investigate the relationship among the presence of ulcer lesions,
      underlying disease, and clinical course in patients with ischemic colitis.
      METHODS: The subjects were 41 patients (10 male and 31 female; mean age 70 years)
      with ischemic colitis who were admitted to and received treatment in our hospital
      from 2000 to 2006. We compared their characteristics and analyzed the mean
      lengths of admission and fasting for 9 patients with ulcer lesions (ulcer group)
      and 32 without (non-ulcer group). RESULTS: The groups with presence and absence
      of ulcer differed significantly only in white blood cell (WBC) count. Lengths of
      fasting and admission were 7.9 d and 17.9 d for the ulcer group and 4.4 d and
      10.7 d for the non-ulcer group, respectively, and significantly longer in the
      ulcer group (P = 0.0057 and 0.0001). There was no correlation between presence of
      ulcer and presence of underlying diseases. CONCLUSION: Lengths of fasting and
      admission were significantly longer in patients with ischemic colitis with ulcer
      than for those without ulcer.

PMID- 17451206
TI  - Effect of preoperative biliary drainage on outcome of classical
      pancreaticoduodenectomy.
AB  - AIM: To investigate the role of preoperative biliary drainage (PBD) in the
      outcome of classical pancreaticoduodenectomy. METHODS: A 10-year retrospective
      data analysis was performed on patients (n = 48) undergoing
      pancreaticoduodenectomy from March 1994 to March 2004 in department of surgery at
      SMS medical college, Jaipur, India. Demographic variables, details of
      preoperative stenting, operative procedure and post operative complications were
      noted. RESULTS: Preoperative biliary drainage was performed in 21 patients
      (43.5%). The incidence of septic complications was significantly higher in
      patients with biliary stent placement (P < 0.05, 0 vs 4). This group of patients
      also had a significantly higher minor biliary leak rate. Mortality and hospital
      stay in each group was comparable. CONCLUSION: Within this study population the
      use of PBD by endoscopic stenting was associated with a high incidence of
      infective complications. These findings do not support the routine use of biliary
      stenting in patients prior to pancreatico-duodenectomy.

PMID- 17451207
TI  - Effects of the myeloperoxidase 463 gene polymorphisms on development of atrophy
      in H pylori infected or noninfected gastroduodenal disease.
AB  - AIM: To investigate the relationship between myelo-peroxidase polymorphisms as a
      host-related factor and atrophy caused by H pylori. METHODS: Our study enrolled
      77 patients. Biopsy materials obtained during gastrointestinal endoscopies were
      evaluated for the presence of H pylori. Polymerase chain reaction-restriction
      fragment length polymorphism assay was used to characterize myeloperoxidase
      genotypes. RESULTS: Forty four patients (57.1%) were Hp (+) and 33 (42.9%) were
      Hp (-). Sixty six (85.7%) had GG genotype, 10 (12.9%) had GA genotype and 1
      (1.29%) had AA genotype. The change in atrophy in relation to neutrophil
      infiltration was significant in Hp (+) patients (P = 0.0001). The change in
      atrophy in relation to neutrophil infiltration in patients with GG genotype was
      significant (P = 0.002). However, the change in atrophy in relation to neutrophil
      infiltration was not significant in patients with Hp (+) GG genotype (r = 0.066,
      P = 0.63). CONCLUSION: Myeloperoxidase genotype is critical for development of
      atrophy in relation to the severity of inflammation. However, it is interesting
      to note that, H pylori does not show any additive effect on development of
      atrophy.

PMID- 17451208
TI  - Prevalence of gastric varices and results of sclerotherapy with N-butyl 2
      cyanoacrylate for controlling acute gastric variceal bleeding.
AB  - AIM: To study the prevalence, predictors and control of bleeding following N
      butyl 2 cyanoacrylate (NBC) sclerotherapy of gastric varix (GV). METHODS: We
      analyzed case records of 1436 patients with portal hypertension, who underwent
      endoscopy during the past five years for variceal screening or upper
      gastrointestinal (GI) bleeding. Fifty patients with bleeding GV underwent
      sclerotherapy with a mean of 2 mL NBC for control of bleeding. Outcome parameters
      were primary hemostasis (bleeding control within the first 48 h), recurrent
      bleeding (after 48 h of esophago-gastro-duodenoscopy) and in-hospital mortality
      were analyzed. RESULTS: The prevalence of GV in patients with portal hypertension
      was 15% (220/1436) and the incidence of bleeding was 22.7% (50/220). Out of the
      50 bleeding GV patients, isolated gastric varices (IGV-I) were seen in 22 (44%),
      gastro-oesophageal varices (GOV) on lesser curvature (GOV-I) in 16 (32%), and GOV
      on greater curvature (GOV-II) in 15 (30%). IGV-I was seen in 44% (22/50) patients
      who had bleeding as compared to 23% (39/170) who did not have bleeding (P <
      0.003). Primary hemostasis was achieved with NBC in all patients. Re-bleeding
      occurred in 7 (14%) patients after 48 h of initial sclerotherapy. Secondary
      hemostasis was achieved with repeat NBC sclerotherapy in 4/7 (57%). Three
      patients died after repeat sclerotherapy, one during transjugular intrahepatic
      portosystemic stem shunt (TIPSS), one during surgery and one due to uncontrolled
      bleeding. Treatment failure-related mortality rate was 6% (3/50). CONCLUSION: GV
      can be seen in 15% of patients with portal hypertension and the incidence of
      bleeding is 22.7%. NBC is highly effective in controlling GV bleeding. In
      hospital mortality of patients with bleeding GV is 6%.

PMID- 17451209
TI  - Detection of small hepatocellular carcinoma: comparison of dynamic enhancement
      magnetic resonance imaging and multiphase multirow-detector helical CT scanning.
AB  - AIM: To compare the gadolinium-enhanced multiphase dynamic magnetic resonance
      imaging (MRI) and multiphase multirow-detector helical CT (MDCT) scanning for
      detection of small hepatocellular carcinoma (HCC). METHODS: MDCT scanning and
      baseline MRI with SE T1-WI and T2-WI sequence combined with FMPSPGR sequence were
      performed in 37 patients with 43 small HCCs. Receiver operating characteristic
      (ROC) curves were plotted to analyze the results for modality. RESULTS: The areas
      below ROC curve (Az) were calculated. There was no statistical difference in
      dynamic enhancement MDCT and MRI. The detection rate of small HCC was 97.5%-97.6%
      on multiphase MDCT scanning and 90.7%-94.7% on MRI, respectively. The sensitivity
      of detection for small HCC on MDCT scanning was higher than that on dynamic
      enhancement MRI. The sensitivity of detection for minute HCC (tumor diameter < or
      = 1 cm) was 90.0%-95.0% on MDCT scanning and 70.0%-85.0% on MRI, respectively.
      CONCLUSION: MDCT scanning should be performed for early detection and effective
      treatment of small HCC in patients with chronic hepatitis and cirrhosis during
      follow-up.

PMID- 17451210
TI  - Aberrant expression of ether a go-go potassium channel in colorectal cancer
      patients and cell lines.
AB  - AIM: To study the expression of ether a go-go (Eag1) potassium channel in
      colorectal cancer and the relation-ship between their expression and clinico
      pathological features. METHODS: The expression levels of Eag1 protein were
      determined in 76 cancer tissues with paired non-cancerous matched tissues as well
      as 9 colorectal adenoma tissues by immunohistochemistry. Eag1 mRNA expression was
      detected in 13 colorectal cancer tissues with paired non-cancerous matched
      tissues and 4 colorectal adenoma tissues as well as two colorectal cancer cell
      lines (LoVo and HT-29) by reverse transcription PCR. RESULTS: The frequency of
      positive expression of Eag1 protein was 76.3% (58/76) and Eag1 mRNA was 76.9%
      (10/13) in colorectal cancer tissue. Expression level of Eag1 protein was
      dependent on the tumor size, lymphatic node metastasis, other organ metastases
      and Dukes' stage (P < 0.05), while not dependent on age, sex, site and degree of
      differentiation. Eag1 protein and mRNA were negative in normal colorectal tissue,
      and absolutely negative in colorectal adenomas except that one case was
      positively stained for Eag1 protein. CONCLUSION: Eag1 protein and mRNA are
      aberrantly expressed in colorectal cancer and occasionally expressed in
      colorectal adenoma. The high frequency of expression of Eag1 in tumors and the
      restriction of normal expression to the brain suggest the potential of this
      protein for diagnostic, prognostic and therapeutic purposes.

PMID- 17451211
TI  - Preventive effect of gelatinizedly-modified chitosan film on peritoneal adhesion
      of different types.
AB  - AIM: To comparatively study the preventive effect of gelatinizedly-modified
      chitosan film on peritoneal adhesions induced by four different factors in rats.
      METHODS: Chitosan was chemically modified by gelatinization, and made into films
      of 60 microm in thickness, and sterilized. Two hundred Sprague-Dawley rats were
      randomly divided into five groups, Sham-operation group (group A), wound-induced
      adhesion group (group B), purified talc-induced adhesion group (group C),
      vascular ligation-induced adhesion group (group D), and infection-induced
      adhesion group (group E), respectively. In each group, the rats were treated with
      different adhesion-inducing methods at the cecum of vermiform processes and then
      were divided into control and experimental subgroups. Serous membrane surface of
      vermiform processes were covered with the films in the experimental subgroups,
      and no films were used in the control subgroups. After 2 and 4 wk of treatments,
      the abdominal cavities were reopened and the adhesive severity was graded blindly
      according to Bhatia's method. The cecum of vermiform processes were resected for
      hydroxyproline (OHP) measurement and pathological examination. RESULTS: Adhesion
      severity and OHP level: After 2 and 4 wk of the treatments, in the experimental
      subgroups, the adhesions were significantly lighter and the OHP levels were
      significantly lower than those of the control subgroups in group B (2 wk: 0.199
      +/- 0.026 vs 0.285 +/- 0.041 microg/mg pr, P < 0.001; 4 wk: 0.183 +/- 0.034 vs
      0.276 +/- 0.03 microg/mg pr, P < 0.001), D (2 wk: 0.216 +/- 0.036 vs 0.274 +/-
      0.040 microg/mg pr, P = 0.004; 4 wk: 0.211 +/- 0.044 vs 0.281 +/- 0.047 microg/mg
      pr, P = 0.003) and E (2 wk: 0.259 +/- 0.039 vs 0.371 +/- 0.040 microg/mg pr, P <
      0.001; 4 wk: 0.242 +/- 0.045 vs 0.355 +/- 0.029 microg/mg pr, P < 0.001), but
      there were no significant differences in groups A (2 wk: 0.141 +/- 0.028 vs 0.137
      +/- 0.026 microg/mg pr, P = 0.737; 4 wk: 0.132 +/- 0.031 vs 0.150 +/- 0.035
      microg/mg pr, P = 0.225) and C (2 wk: 0.395 +/- 0.044 vs 0.378 +/- 0.043
      microg/mg pr, P = 0.387; 4 wk: 0.370 +/- 0.032 vs 0.367 +/- 0.041 microg/mg pr, P
      = 0.853); Pathological changes: In group B, the main pathological changes were
      fibroplasias in the treated serous membrane surface and in group D, the
      fibroplasia was shown in the whole layer of the vermiform processes. In group E,
      the main pathological changes were acute and chronic suppurative inflammatory
      reactions. These changes were lighter in the experimental subgroups than those in
      the control subgroups in the three groups. In group C, the main changes were
      foreign body giant cell and granuloma reactions and fibroplasias in different
      degrees, with no apparent differences between the experimental and control
      subgroups. CONCLUSION: The gelatinizedly-modified chitosan film is effective on
      preventing peritoneal adhesions induced by wound, ischemia and infection, but the
      effect is not apparent in foreign body-induced adhesion.

PMID- 17451212
TI  - Endoscopic resection of an ampullary carcinoid presenting with upper
      gastrointestinal bleeding: a case report and review of the literature.
AB  - Ampullary carcinoid is a rare tumor that can present with gastrointestinal
      bleeding, obstructive jaundice or pancreatitis. Some of these tumors are
      associated with Von Recklinghausen disease. The usual surgical options are a
      biliary-enteric anastomosis, Whipple procedure or rarely a local resection. The
      mean survival does not appear to be much different after a
      pancreaticoduodenectomy versus local surgical excision. We report a very rare
      case of a non-metastatic ampullary carcinoid causing upper gastrointestinal
      bleeding, which was managed by endoscopic ampullectomy.

PMID- 17451213
TI  - Multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated
      hepatocellular carcinoma in a patient with alcohol-related liver cirrhosis.
AB  - We describe a rare case of the transformation of a dysplastic nodule into well
      differentiated hepato-cellular carcinoma (HCC) in a 56-year-old man with alcohol
      related liver cirrhosis. Ultrasound (US) disclosed a 10 mm hypoechoic nodule and
      contrast enhanced US revealed a hypovascular nodule, both in segment seven. US
      guided biopsy revealed a high-grade dysplastic nodule characterized by enhanced
      cellularity with a high N/C ratio, increased cytoplasmic eosinophilia, and slight
      cell atypia. One year later, the US pattern of the nodule changed from hypoechoic
      to hyperechoic without any change in size or hypovascularity. US-guided biopsy
      revealed well-differentiated HCC of the same features as shown in the first
      biopsy, but with additional pseudoglandular formation and moderate cell atypia.
      Moreover, immunohistochemical staining of cyclase-associated protein 2, a new
      molecular marker of well-differentiated HCC, turned positive. This is the first
      case of multistep hepatocarcinogenesis from a dysplastic nodule to well
      differentiated HCC within one year in alcohol-related liver cirrhosis.

PMID- 17451214
TI  - Common bile duct schwannoma: a case report and review of literature.
AB  - Schwannoma is a myelin sheath tumor complicated with neurofibroma,
      neurofibromatosis and neurogenic sarcoma. Peripheral nerve sheath tumors
      represent 2%-6% of gastrointestinal tract stromal tumors (GIST), but there are
      deficient data about location of neurogenic tumors in the biliary system and only
      nine cases of schwannoma of the extrahepatic biliary tract have been reported.
      These tumors are clinically non-specific. They are usually symptomatic by
      compressing the close or adjacent structures when being retroperitoneal, and
      their preoperative diagnosis is extremely difficult. This paper reviews the
      literature data and describes a case of schwannoma of the common bile duct
      associated with cholestasis in a healthy young woman, diagnosed and treated in
      our department. This case is of interest on account of the complexity of its
      diagnosis and the atypical macroscopic growth pattern of the tumor.

PMID- 17451215
TI  - Foregut duplication cysts of the stomach with respiratory epithelium.
AB  - Gastrointestinal duplication is a congenital rare disease entity. Gastric
      duplication cysts seem to appear even more rarely. Herein, two duplications cysts
      of the stomach in a 46 year-old female patient are presented. Abdominal computed
      tomography demonstrated a cystic lesion attached to the posterior aspect of the
      gastric fundus, while upper gastrointestinal endoscopy was negative. An
      exploratory laparotomy revealed a non-communicating cyst and a smaller similar
      cyst embedded in the gastrosplenic ligament. Excision of both cysts along with
      the spleen was performed and pathology reported two smooth muscle coated cysts
      with a pseudostratified ciliated epithelial lining (respiratory type).

PMID- 17451216
TI  - Melena: a rare complication of duodenal metastases from primary carcinoma of the
      lung.
AB  - Small bowel metastases from primary carcinoma of the lung are very uncommon and
      occur usually in patients with terminal stage disease. These metastases are
      usually asymptomatic, but may present as perforation, obstruction, malabsorption,
      or hemorrhage. Hemorrhage as a first presentation of small bowel metastases is
      extremely rare and is related to very poor patient survival. We describe a case
      of a 61- year old patient with primary adenocarcinoma of the lung, presenting
      with melena as the first manifestation of small bowel metastasis. Both primary
      tumor and metastatic lesions were diagnosed almost simultaneously. Upper
      gastrointestinal endoscopy performed with a colonoscope revealed active bleeding
      from a metastatic tumor involving the duodenum and the proximal jejunum.
      Histological examination and immunohistochemical staining of the biopsy specimen
      strongly supported the diagnosis of metastatic lung adenocarcinoma, suggesting
      that small bowel metastases from primary carcinoma of the lung occur usually in
      patients with terminal disease and rarely produce symptoms. Gastrointestinal
      bleeding from metastatic small intestinal lesions should be included in the
      differential diagnosis of gastrointestinal blood loss in a patient with a known
      bronchogenic tumor.

PMID- 17451217
TI  - Liver toxicity of rosuvastatin therapy.
AB  - We report here a case of clinically significant liver toxicity after a brief
      course of rosuvastatin, which is the first statin approved by the regulatory
      authorities since the withdrawal of cerivastatin. Whether rosuvastatin has a
      greater potential compared with other statins to damage the liver is unclear and
      the involved mechanisms are also unknown. However, rosuvastatin is taken up by
      hepatocytes more selectively and more efficiently than other statins, and this
      may reasonably represent an important variable to explain the hepatotoxic
      potential of rosuvastatin. Our report supports the view that a clinically
      significant risk of liver toxicity should be considered even when rosuvastatin is
      given at the range of doses used in common clinical practice.

PMID- 17451218
TI  - Capsule endoscopy retention as a helpful tool in the management of a young
      patient with suspected small-bowel disease.
AB  - Capsule endoscopy is an easy and painless procedure permitting visualization of
      the entire small-bowel during its normal peristalsis. However, important problems
      exist concerning capsule retention in patients at risk of small bowel
      obstruction. The present report describes a young patient who had recurrent
      episodes of overt gastrointestinal bleeding of obscure origin, 18 years after
      small bowel resection in infancy for ileal atresia. Capsule endoscopy was
      performed, resulting in capsule retention in the distal small bowel. However,
      this event contributed to patient management by clearly identifying the site of
      obstruction and can be used to guide surgical intervention, where an anastomotic
      ulcer is identified.

PMID- 17451220
TI  - Gallstone ileus: report of two cases and review of the literature.
AB  - Gallstone ileus is a rare disease and accounts for 1%-4% of all cases of
      mechanical intestinal obstruction. It usually occurs in the elderly with a female
      predominance and may result in a high mortality rate. Its diagnosis is difficult
      and early diagnosis could reduce the mortality. Surgery remains the mainstay of
      treatment. We report two cases of gallstone ileus. The first was a 78-year old
      woman who had a 2-d history of vomiting and epigastralgia. Plain abdominal film
      suggested small bowel obstruction clinically attributed to adhesions. Later on,
      gallstone ileus was diagnosed by abdominal computed tomography (CT) based on the
      presence of pneumobilia, bowel obstruction, and an ectopic stone within the
      jejunum. She underwent emergent laparotomy with a one-stage procedure of
      enterolithotomy, cholecystectomy and fistula repair. The second case was a 76
      year old man with a 1-wk history of epigastralgia. Plain abdominal film showed
      two round calcified stones in the right upper quadrant. Fistulography confirmed
      the presence of a cholecystoduodenal fistula and gallstone ileus was also
      diagnosed by abdominal CT. We attempted to remove the stones endoscopically, but
      failed leading to an emergent laparotomy and the same one-stage procedure as for
      the first case. The postoperative courses of the two cases were uneventful.
      Inspired by these 2 cases we reviewed the literature on the cause, diagnosis and
      treatment of gallstone ileus.

PMID- 17451219
TI  - Simultaneous development of diabetic ketoacidosis and Hashitoxicosis in a patient
      treated with pegylated interferon-alpha for chronic hepatitis C.
AB  - Classical interferon-alpha has been shown to be correlated with the development
      of a variety of autoimmune disorders. A 38 year-old female patient developed
      simultaneously diabetic ketoacidosis and hyperthyroidism 5 mo following
      initiation of treatment with pegylated interferon-alpha and ribavirin for chronic
      hepatitis C. High titers of glutamic acid decarboxylase, antinuclear and thyroid
      (thyroid peroxidase and thyroglobulin) antibodies were detected. Antiviral
      treatment was withdrawn and the patient was treated with insulin for insulin
      dependent diabetes mellitus and propranolol for hyperthyroidism. Twelve months
      after cessation of pegylated interferon-alpha therapy the patient was euthyroid
      without any medication but remained insulin-dependent.

PMID- 17451221
TI  - Primary intestinal malignant fibrous histiocytoma: two case reports.
AB  - Malignant fibrous histiocytoma (MFH) occurs most commonly in the extremities and
      trunk, but rarely in the intestine. Here we report two cases of primary
      intestinal MFH. The first case was a 70-year old man admitted for recurrent right
      lower quadrant abdominal pain. At laparotomy, a tumor was found originating from
      the cecum, with a suspicious metastatic nodule on the surface of the right lobe
      of the liver. A right hemicolectomy was performed followed by an ileotransverse
      end-to-end anastomotic reconstruction. The second case was a 43-year old man with
      intussusceptions of the small intestine. An emergent laparotomy revealed 4
      pedunculated masses in the small bowel and a partial resection of the small
      intestine was performed. Though the symptoms were not typical, based on
      histological and immunohistochemical studies, the patients were diagnosed as MFH
      of the intestine. They were not treated with chemotherapy or radiotherapy and
      both died within 3 mo. MFH of the intestine is an extremely rare neoplasm with an
      aggressive biological behavior. The pathogenesis of this disease has not been
      clarified to date. Complete surgical excision is preferred, adjuvant chemotherapy
      or radiotherapy may be advisable.

PMID- 17451222
TI  - Eosinophilic gastroenteritis with ascites and hepatic dysfunction.
AB  - Eosinophilic gastroenteritis is a rare gastrointestinal disorder with
      eosinophilic infiltration of the gastrointestinal wall and various
      gastrointestinal dysfunctions. Diagnosis requires a high index of suspicion and
      exclusion of various disorders that are associated with peripheral eosinophilia.
      We report a case of eosinophilic gastroenteritis, which had features of the
      predominant subserosal type presenting with ascites and hepatic dysfunction, and
      which responded to a course of low-dose steroid.

PMID- 17451223
TI  - What caused the increase of autoimmune and allergic diseases: a decreased or an
      increased exposure to luminal microbial components?

PMID- 17451224
TI  - Photo-induced valence tautomerism in Co complexes.
AB  - A number of photofunctional molecular compounds have been developed recently.
      Typical examples of these are phototunable valence tautomeric compounds, which
      are now attracting great attention. When the charge-transfer bands of some Co
      valence tautomeric compounds are excited at low temperature, metastable redox
      isomers can be created after irradiation. The lifetimes of the metastable states
      can be more than several hours. These transformations can involve changes in the
      magnetic properties of the compounds, as well as their color. Hence, these
      compounds can be regarded as novel photomagnetic materials. The photoresponsive
      behaviors of these valence tautomeric compounds are similar to those of spin
      crossover complexes (light-induced excited spin-state trapping effects).

PMID- 17451225
TI  - A novel logic-based approach for quantitative toxicology prediction.
AB  - There is a pressing need for accurate in silico methods to predict the toxicity
      of molecules that are being introduced into the environment or are being
      developed into new pharmaceuticals. Predictive toxicology is in the realm of
      structure activity relationships (SAR), and many approaches have been used to
      derive such SAR. Previous work has shown that inductive logic programming (ILP)
      is a powerful approach that circumvents several major difficulties, such as
      molecular superposition, faced by some other SAR methods. The ILP approach
      reasons with chemical substructures within a relational framework and yields
      chemically understandable rules. Here, we report a general new approach, support
      vector inductive logic programming (SVILP), which extends the essentially
      qualitative ILP-based SAR to quantitative modeling. First, ILP is used to learn
      rules, the predictions of which are then used within a novel kernel to derive a
      support-vector generalization model. For a highly heterogeneous dataset of 576
      molecules with known fathead minnow fish toxicity, the cross-validated
      correlation coefficients (R2CV) from a chemical descriptor method (CHEM) and
      SVILP are 0.52 and 0.66, respectively. The ILP, CHEM, and SVILP approaches
      correctly predict 55, 58, and 73%, respectively, of toxic molecules. In a set of
      165 unseen molecules, the R2 values from the commercial software TOPKAT and SVILP
      are 0.26 and 0.57, respectively. In all calculations, SVILP showed significant
      improvements in comparison with the other methods. The SVILP approach has a major
      advantage in that it uses ILP automatically and consistently to derive rules,
      mostly novel, describing fragments that are toxicity alerts. The SVILP is a
      general machine-learning approach and has the potential of tackling many problems
      relevant to chemoinformatics including in silico drug design.

PMID- 17451226
TI  - Stereoisomeric identification of norephedrine derived from methamphetamine or
      amphetamine: urinalysis results of 33 methamphetamine abusers and 1 amphetamine
      abuser in Japan.
AB  - Stereoisomeric identification of norephedrine (NE) derived from methamphetamine
      (MA) or amphetamine (AM) was investigated by SIM-GC/MS assay using the urine of
      33 MA abusers and 1 AM abuser. The assay simultaneously identified TFA
      derivatized MA and AM metabolites, including AM, p-hydroxyl-MA (p-HMA), and p
      hydroxyl-AM (p-HAM). The analysis lasted approximately 43 min, with a signal-to
      noise ratio of >or=3 and a detection limit of 50 ng/mL. Among 12 urine samples
      from different subjects, only the S (+) form of MA and its metabolites (AM, p
      HMA, p-HAM) was detected, however, a (1R,2S)-(-)-NE stereoisomer was also
      identified. Among the urine samples of two subjects, only the R (-) form of MA
      and its metabolites (AM, p-HMA, p-HAM) was detected, while NE was not detected.
      Following urinalysis of urine obtained from 19 MA abusers and 1 AM abuser, only
      the (1R,2S)-(-)-NE stereoisomer was identified, while unmetabolized MA, AM, and
      their metabolites (p-HMA, p-HAM), showed stereoselective metabolism. Although
      (1R,2S)-(-)-ephedrine (EP) alone was found in the urine of 1 (S)-(+)-MA user and
      1 (S)-(+)- and (R)-(-)-MA user among 33 MA users, it was not present in the urine
      of the remaining 31 subjects. Therefore, (1R,2S)-(-)-NE was likely not of (1R,2S)
      (-)-EP origin and was most likely from (S)-(+)-AM of the MA metabolite. The
      production ratio of (1R,2S)-(-)-NE to (S)-(+)-AM ranged from 0.01 to 0.25 in MA
      abusers and was 0.12 in AM abusers.

PMID- 17451227
TI  - Enhancement of the detection power of surface plasmon resonance measurements by
      optimization of the reflection angle.
AB  - The detection limit of surface plasmon resonance (SPR) measurements has been
      improved by a factor of approximately 2-3.5 if the angle of incidence was near to
      the reflection minimum of the SPR resonance curve instead at the position of the
      steepest slope, the standard alignment in SPR imaging. The enhancement of the
      detection power, a result of signal-to-noise optimization, is demonstrated by
      applying a photodiode and a CCD camera for SPR detection. The experimental data
      are compared with data expected from theory.

PMID- 17451228
TI  - The insertion of the antimicrobial peptide dicynthaurin monomer in model
      membranes: thermodynamics and structural characterization.
AB  - This paper is focused on the thermodynamics and the structural investigation of
      the interaction of the antimicrobial peptide dicynthaurin monomer with model
      lipid membranes composed of mixtures of 1-palmitoyl-2-oleyl-glycerophosphocholine
      and -glycerophosphoglycerol. The thermodynamic binding parameters as obtained by
      isothermal titration calorimetry reveal strong binding toward the lipid model
      system dominated by large chemical binding constants which exceeds the
      electrostatic binding effects and thus suggests insertion of the amphipathic
      alpha-helical peptide into the hydrophobic membrane core. Circular dichroism
      study shows that the peptide exhibits trans-membrane alpha-helix secondary
      structure. Neutron diffraction measurements using partially deuterated sequences
      were successfully applied to determine the orientation of the peptide thus
      proving insertion into the hydrophobic membrane core. This insertion and the
      formation of higher order porelike aggregates is assumed to be the most relevant
      event in microbial membrane perturbation that in vivo finally leads to bacterial
      cell death on a fast time scale.

PMID- 17451229
TI  - Destabilization of DJ-1 by familial substitution and oxidative modifications:
      implications for Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by
      oxidative stress and protein aggregation. Both toxic phenomena are mitigated by
      DJ-1, a homodimeric protein with proposed antioxidant and chaperone activities.
      The neuroprotective function of DJ-1 is modulated by oxidation of cysteine 106, a
      residue that may act as an oxidative stress sensor. Loss-of-function mutations in
      the DJ-1 gene have been linked to early onset PD, and age-dependent over
      oxidation of DJ-1 is thought to contribute to sporadic PD. The familial mutant
      L166P fails to dimerize and is rapidly degraded, suggesting that protein
      destabilization accounts for the dysfunction of this mutant. In this study, we
      investigated how the structure and stability of DJ-1 are impacted by two other
      pathogenic substitutions (M26I and E64D) and by over-oxidation with H2O2. Whereas
      the recombinant wild-type protein and E64D both adopted a stable dimeric
      structure, M26I showed an increased propensity to aggregate and decreased
      secondary structure. Similar to M26I, over-oxidized wild-type DJ-1 exhibited
      reduced secondary structure, and this property correlated with destabilization of
      the dimer. The engineered mutant C106A had a greater thermodynamic stability and
      was more resistant to oxidation-induced destabilization than the wild-type
      protein. These results suggest that (i) the M26I substitution and over-oxidation
      destabilize dimeric DJ-1, and (ii) the oxidation of cysteine 106 contributes to
      DJ-1 destabilization. Our findings provide a structural basis for DJ-1
      dysfunction in familial and sporadic PD, and they suggest that dimer
      stabilization is a reasonable therapeutic strategy to treat both forms of this
      disorder.

PMID- 17451230
TI  - Predictions of the geometries and fluorescence emission energies of
      oxyluciferins.
AB  - The complete active space self-consistent field (CASSCF) method and
      multiconfigurational second-order perturbation theory (CASPT2) have been used to
      study the structures and spectra of oxyluciferins (OxyLH2). The ground and lowest
      lying singlet excited states geometries have been optimized using CASSCF. CASPT2
      has been used to predict relaxed emission energies. The focus is on the lowest
      lying singlet excited states of the anionic keto and enol forms of OxyLH2(-1) at
      the optimized excited-state geometries. The planar keto and enol forms of OxyLH2(
      1) are minima on both the S0 and the S1 potential energy surfaces. The twisted
      keto and enol forms of OxyLH2(-1) are transition states on the S0 and S1
      potential energy surfaces. The S1 --> S0 fluorescence emission energies are in
      the range of 54.2-58.4 kcal/mol for the anionic planar keto forms of OxyLH2, and
      in the range of 55.7-63.2 kcal/mol for the anionic enol forms of OxyLH2. S0 and
      S1 potential energy surfaces and thus are not implicated in the emission spectra
      in the gas phase.

PMID- 17451231
TI  - Temperature changes visualization during chemical wave propagation.
AB  - Magnetic resonance imaging was used for two-dimensional temperature visualization
      of chemical waves propagation in the autocatalytic exothermal reaction of
      thiosulfate oxidation by chlorite. The technique presented is based on the
      temperature dependence of the water chemical shift. Temperature maps were
      acquired by employing the TurboFLASH imaging method. The results obtained allow
      one to judge about directions of buoyancy flows. Two types of convection critical
      modes in a vertical tube during the wave propagation were detected.

PMID- 17451232
TI  - Discovery of 4-aminobutyric acid derivatives possessing anticonvulsant and
      antinociceptive activities: a hybrid pharmacophore approach.
AB  - Antiepileptic drugs are often utilized in the treatment of neuropathic pain. The
      present study aims at the design and synthesis of newer gamma-aminobutyric acid
      (GABA) derivatives with the combination of aryl semicarbazone and the GABA
      pharmacophores in order to develop a multifunctional drug useful in the treatment
      of neurological disorders like epilepsy and neuropathic pain. Various GABA
      semicarbazones were synthesized and screened for anticonvulsant, peripheral
      analgesic, antiallodynic, and antihyperalgesic activities. The structures of the
      synthesized compounds were confirmed by the use of their spectral data in
      addition to elemental analysis. The synthesized derivatives of the inhibitory
      neurotransmitter GABA produced anticonvulsant and antinociceptive actions in the
      acetic acid induced writhing test and peripheral nerve injury (chronic
      constriction injury and L5 spinal nerve ligation) models of neuropathic pain. The
      underlying mechanisms are expected to be enhancement of peripheral GABAergic
      neurotransmission owing to their activity in the scPIC screen and due to various
      reports on the involvement of GABAergic pathway in peripheral models of
      neuropathic pain.

PMID- 17451233
TI  - Synthesis and study of L-dopa-glutathione codrugs as new anti-Parkinson agents
      with free radical scavenging properties.
AB  - A series of novel molecular combinations (1-4), in which L-dopa (LD) is linked
      covalently via an amide bond with glutathione (GSH), were synthesized and
      evaluated as potential anti-Parkinson agents with antioxidant properties. These
      conjugates were characterized by evaluating solubility, chemical and enzymatic
      stabilities, and apparent partition coefficient (log P). Derivatives 2 and 4 were
      tested for their radical scavenging activities, by use of a test involving the
      Fe(II)/H2O2-induced degradation of deoxyribose. In this study, the antioxidant
      efficacy of codrugs 1 and 3 was also assessed through the evaluation of plasmatic
      activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx).
      Furthermore, the central nervous effects and rat striatal concentration of LD and
      dopamine (DA) have been evaluated after oral administration of codrugs 1 and 3.
      Tested compounds prolonged the plasma LD levels and were able to induce sustained
      delivery of DA in rat striatum with respect to an equimolar dose of LD. The
      results suggest that compounds 1 and 3 could represent useful new anti-Parkinson
      agents devoid of the pro-oxidant effects associated with LD therapy and
      potentially able to restore the GSH depletion evidenced in the substantia nigra
      pars compacta (SNpc) of PD patients.

PMID- 17451234
TI  - Identification of inhibitors of protein kinase B using fragment-based lead
      discovery.
AB  - Using fragment-based screening techniques, 5-methyl-4-phenyl-1H-pyrazole (IC50 80
      microM) was identified as a novel, low molecular weight inhibitor of protein
      kinase B (PKB). Herein we describe the rapid elaboration of highly potent and
      ligand efficient analogues using a fragment growing approach. Iterative structure
      based design was supported by protein-ligand structure determinations using a PKA
      PKB "chimera" and a final protein-ligand structure of a lead compound in PKBbeta
      itself.

PMID- 17451235
TI  - Rapid evolution of 6-phenylpurine inhibitors of protein kinase B through
      structure-based design.
AB  - 6-phenylpurines were identified as novel, ATP-competitive inhibitors of protein
      kinase B (PKB/Akt) from a fragment-based screen and were rapidly progressed to
      potent compounds using iterative protein-ligand crystallography with a PKA-PKB
      chimeric protein. An elaborated lead compound showed cell growth inhibition and
      effects on cellular signaling pathways characteristic of PKB inhibition.

PMID- 17451236
TI  - Analysis of phase transition pathways in X3H(SO4)2 (X=Rb, NH4, K, Na): variable
      temperature single-crystal X-ray diffraction studies.
AB  - Evaluation of phase transitions in a series of hydrogen sulfates (Rb3H(SO4)2,
      (NH4)3H(SO4)2, K3 H(SO4)2, and Na3H(SO4)2) based on the single-crystal structure
      analysis has revealed the exact nature of such transitions and has sorted out the
      various ambiguities involved in earlier literature. Rb3H(SO4)2 at 293 K is C2/c.
      It is isostructural to its ammonium analogue, (NH4)3H(SO4)2, at room temperature.
      However, the variable temperature single-crystal diffraction studies indicate
      that the phase transition mechanism is different. When cooled to 100 K, the
      structure of Rb3H(SO4)2 remains C2/c. When heated to 350 K, it transforms to C2/m
      (with double the volume at room temperature), which changes to C2/c (with 4 times
      the volume at room temperature) at 425 K. The high-temperature (420 K) structural
      phase transition in (NH4)3H(SO4)2 is shown to be Rm. The structure of Na3H(SO4)2
      remains invariant (P21/c) throughout the range of 100-500 K except for the usual
      contraction of the unit cell at 100 K and expansion at 500 K. The structural
      phase transitions with temperature for the compound K3H(SO4)2 are very different
      from those claimed in earlier literature. The hydrogen atom participating in the
      crucial hydrogen bond joining the two sulfate tetrahedra controls the structural
      phase transitions at low temperatures in all four compounds. The distortion of
      the SO4 tetrahedra and the coordination around the metal atom sites control the
      phase evolution in the Rb compound, while the Na and K analogues show no phase
      transitions at high temperature, and the NH4 system transforms to a higher
      symmetry space group resulting in a disorder of the sulfate moiety.

PMID- 17451237
TI  - First example of the solid-state thermal cyclometalation of ligated benzophenone
      imine giving novel luminescent platinum(II) species.
AB  - The (benzophenone imine)platinum(II) compounds trans-[PtCl2(Ph2C=NH)(RR'SO)] [R,
      R'=Me, Me (2); n-Pr, n-Pr (3); (CH2)4 (4); Me, Ph (5); Me, p-MeC6H4 (6)] were
      prepared by the reaction of Ph2C=NH with K[PtCl3(RR'SO)], obtained in situ from
      K2[PtCl4] and the corresponding sulfoxide, giving 2-6 as well as cis
      [PtCl2(Ph2C=NH)2] (1) as a minor product. The complexes were characterized by 1H,
      13C, and 195Pt NMR and IR spectroscopy, electrospray ionization mass
      spectrometry, and C, H, and N elemental analysis. The X-ray crystallography of 1
      enables confirmation of the cis configuration of the complex, while in 2 and
      4.1/2CHCl3, the imine and sulfoxide ligands are mutually trans. The solid-state
      structure of 4.1/2CHCl3 consists of two dimeric Pt moieties representing a rather
      weak Pt...Pt interaction. The dimeric architecture of 4.1/2CHCl3 is enhanced by
      the hydrogen bonding between imine H atoms and O atoms. The orthometalation of 1
      and 2-6 proceeds both in the solid phase and in a toluene suspension, leading to
      the formation of [PtCl{Ph(C6H4)C=NH}(Ph2C=NH)] (7) and
      [PtCl{Ph(C6H4)C=NH}(RR'SO)] (8-12), respectively, isolated in nearly quantitative
      yields. Complexes 8-12 are emissive at room temperature both in solution
      (lambdaemmax approximately 535 nm) and in the solid state (lambdaemmax 560-610
      nm), with excited-state lifetimes of ca. 300-600 ns, representing a new family of
      PtII-based luminescent complexes. Compounds 8 and 10 have been characterized by X
      ray analysis, confirming the square-planar coordination geometry of the metal
      center with the almost planar platinacycles. In 8, the asymmetric unit contains
      two independent Pt molecules, while in 10, it includes four Pt molecules linked
      by the intermolecular hydrogen-bonding network between the NH group and Cl atoms.

PMID- 17451238
TI  - Solvent tuning from normal to inverted marcus region of intramolecular electron
      transfer in ferrocene-based organic radicals.
AB  - The solvent dependence of spectroscopic data of two neutral paramagnetic donor
      acceptor dyads, based on a polychlorinated triphenylmethyl radical acceptor unit
      linked through a vinylene pi-bridge to a ferrocene (compound 1) or a
      nonamethylferrocene donor (compound 2) unit, is described. Both compounds exhibit
      broad absorptions in the near-IR region, with band maxima appearing around 1000
      and 1500 nm for 1 and 2, respectively. These bands correspond to the excitation
      of a neutral DA ground state to the charge-separated D+A- state, indicative of an
      intramolecular electron-transfer process. Compounds 1 and 2 show two reversible
      one-electron redox processes associated with the oxidation of the ferrocene and
      the reduction of the polychlorotriphenylmethyl radical subunits. The solvent
      dependence of the redox potentials was also investigated, allowing the
      determination of the redox asymmetries DeltaG degrees of both dyads. The latter
      values, along with the experimental Eopt spectroscopic data, allow us to
      estimate, using the total energy balance Eopt = lambda + DeltaG degrees , the
      reorganization energy values, lambda, and their solvent polarity dependence.
      Since DeltaG degrees and lambda are of the same order of magnitude but exhibit
      opposite trends in their solvent polarity dependence, a unique shift from the
      normal to the inverted Marcus region with the change in solvent polarity is
      found. The kinetics of the charge recombination step of the excited charge
      separated D+A- state was studied by picosecond transient absorption spectroscopy,
      which allows us to observe and monitor for the first time the charge-separated
      D+A- state, thereby confirming unambiguously the photoinduced electron-transfer
      phenomena.

PMID- 17451239
TI  - Directed evolution of 2-keto-3-deoxy-6-phosphogalactonate aldolase to replace 3
      deoxy-D-arabino-heptulosonic acid 7-phosphate synthase.
AB  - Directed evolution of 2-keto-3-deoxy-6-phosphogalactonate (KDPGal) aldolase for
      microbial synthesis of shikimate pathway products provides an alternate strategy
      to circumvent the competition for phosphoenolpyruvate between 3-deoxy-D-arabino
      heptulosonic acid 7-phosphate (DAHP) synthase and the
      phosphoenolpyruvate:carbohydrate phosphotransferase system in Escherichia coli.
      E. coli KDPGal aldolase was evolved using a combination of error-prone polymerase
      chain reaction, DNA shuffling, and multiple-site-directed mutagenesis to afford
      KDPGal aldolase variant NR8.276-2, which exhibits a 60-fold improvement in the
      ratio kcat/KM relative to that of wild-type E. coli KDPGal aldolase in catalyzing
      the addition of pyruvate to d-erythrose 4-phosphate to form DAHP. On the basis of
      its nucleotide sequence, NR8.276-2 contains seven amino acid changes from the
      wild-type E. coli KDPGal aldolase. Amplified expression of NR8.276-2 in the DAHP
      synthase and shikimate dehydrogenase-deficient E. coli strain NR7 under fed-batch
      fermentor-controlled cultivation conditions resulted in synthesis of 13 g/L 3
      dehydroshikimic acid in 6.5% molar yield from glucose. Increased coexpression of
      the irreversible downstream enzyme 3-dehydroquinate synthase increased production
      of 3-dehydroshikimic acid to 19 g/L in 9.7% molar yield from glucose.
      Coamplification with transketolase, which increases d-erythrose 4-phosphate
      availability, afforded 16 g/L 3-dehydroshikimic acid in 8.5% molar yield.

PMID- 17451240
TI  - Spectroscopic and computational evaluation of the structure of the high-spin
      Fe(IV)-oxo intermediates in taurine: alpha-ketoglutarate dioxygenase from
      Escherichia coli and its His99Ala ligand variant.
AB  - The Fe(II)- and alpha-ketoglutarate (alphaKG)-dependent dioxygenases activate O2
      for cleavage of unactivated C-H bonds in their substrates. The key intermediate
      that abstracts hydrogen in the reaction of taurine:alphaKG dioxygenase (TauD), a
      member of this enzyme family, was recently characterized. The intermediate,
      denoted J, was shown to contain an iron(IV)-oxo unit. Other important structural
      features of J, such as the number, identity, and disposition of ligands in the
      Fe(IV) coordination sphere, are not yet understood. To probe these important
      structural features, a series of models for J with the Fe(IV) ion coordinated by
      the expected two imidazole (from His99 and His255), two carboxylate (succinate
      and Asp101), and oxo ligands have been generated by density functional theory
      (DFT) calculations, and spectroscopic parameters (Mossbauer isomer shift,
      quadrupole splitting, and asymmetry parameter, 57Fe hyperfine coupling tensor,
      and zero field splitting parameters, D and E/D) have been calculated for each
      model. The calculated parameters of distorted octahedral models for J, in which
      one of the carboxylates serves as a monodentate ligand and the other as a
      bidentate ligand, and a trigonal bipyramidal model, in which both carboxylates
      serve as monodentate ligands, agree well with the experimental parameters,
      whereas the calculated parameters of a square pyramidal model, in which the oxo
      ligand is in the equatorial plane, are inconsistent with the data. Similar
      analysis of the Fe(IV) complex generated in the variant protein with His99, the
      residue that contributes the imidazole ligand cis to the oxo group, replaced by
      alanine suggests that the deleted imidazole is replaced by a water ligand. This
      work lends credence to the idea that the combination of Mossbauer spectroscopy
      and DFT calculations can provide detailed structural information for reactive
      intermediates in the catalytic cycles of iron enzymes.

PMID- 17451241
TI  - Observable azacyclobutenone ylides with antiaromatic character from 2-diazoacetyl
      azaaromatics.
AB  - Azacyclobutenone ylides 2 and 11 were generated in solution by laser flash
      photolysis of 2-diazoacetylpyridine (1) and 3-diazoacetylpyridazine (10),
      respectively, together with the corresponding ketenes. The ylides were identified
      by their characteristic IR and UV spectra: 2, nu (CH3CN) 1725 cm(-1), lambdamax
      360 and 550 (br) nm; 11, nu (CH3CN) 1776 cm(-1), lambdamax 370 and 550 (br) nm. 2
      Triisopropylsilyldiazoacetylpyridine 20 upon photolysis at 5 degrees C in CH3CN
      forms the ylide 21 as a rather persistent (T1/2 2 h at 25 degrees C) purple
      solution, nu (CH3CN) 1718 cm(-1), lambdamax 245, 378 and 546 (br) nm, but no
      ketene is observed. Quinolyl ylide 14 and pyridyl ylides 17 and 19 with Me and 2
      pyridyl substituents, respectively, with characteristic IR and UV spectra were
      also generated. The 1H NMR spectrum of the pyridyl ring of 21 shows substantial
      upfield shifts relative to those of 20. Calculated nucleus-independent chemical
      shifts (NICS) for 2, 11, and 21 are comparable to those for benzocyclobutadiene
      (22) and benzocyclobutenone enolate (23), with substantial positive values for
      the 4-membered rings, while the NICS values for the 6-membered rings are
      significantly more positive than for benzene or pyridine. Significant bond
      alternation is also found in the calculated ylide structures, and these results
      suggest strong antiaromatic character for the 4-membered rings of 2, 11, 14, 17,
      19, and 21, and greatly reduced aromatic character for the 6-membered rings.

PMID- 17451242
TI  - Sculpting the bicyclo[3.1.0]hexane template of carbocyclic nucleosides to improve
      recognition by herpes thymidine kinase.
AB  - The replacement of the furanose ring by a cyclopentane in nucleosides generates a
      group of analogues known generically as carbocyclic nucleosides. These compounds
      have increased chemical and enzymatic stability due to the absence of a true
      glycosyl bond that characterizes conventional nucleosides. The additional fusion
      of a cyclopropane ring to the cyclopentane produces a bicyclo[3.1.0]hexane system
      that depending on its location relative to the nucleobase is able to lock the
      embedded cyclopentane ring into conformations that mimic the typical north and
      south conformations of the furanose ring in conventional nucleosides. These
      bicyclo[3.1.0]hexane templates have already provided important clues to
      differentiate the contrasting conformational preferences between kinases and
      polymerases. Herein, we describe the design, synthesis, and phosphorylation
      pattern of a new bicyclo[3.1.0]hexane thymidine analogue that seems to possess an
      ideal spatial distribution of pharmacophores for an optimal interaction with
      herpes simplex 1 thymidine kinase. The bicyclo[3.1.0]hexane template represents a
      privileged rigid template for sculpting other carbocyclic nucleosides to meet the
      demands of specific receptors.

PMID- 17451243
TI  - Aryl to aryl palladium migration in the Heck and Suzuki coupling of o
      halobiaryls.
AB  - A novel 1,4-palladium migration between the o- and o'-positions of biaryls has
      been observed in organopalladium intermediates derived from o-halobiaryls. The
      organopalladium intermediates generated by this migration have been trapped
      either by a Heck reaction employing ethyl acrylate or by Suzuki cross-coupling
      using arylboronic acids. This palladium migration can be activated or deactivated
      by choosing the appropriate reaction conditions. Chemical and computational
      evidence supports the presence of an equilibrium that correlates with the C-H
      acidity of the available arene positions.

PMID- 17451245
TI  - Transition metal migration upon attempting the Wolff rearrangement of an Ir(III)
      five-membered metallacycle.

PMID- 17451246
TI  - A heterogeneous PNA-based SERS method for DNA detection.

PMID- 17451247
TI  - Nanoscale tunable proton/hydrogen sensing: evidence for surface-adsorbed hydrogen
      atom on architectured palladium nanoparticles.

PMID- 17451248
TI  - Ring-opening reaction of cyclopropanated [60]fullerenes: unexpected
      transformation of methano[60]fullerenes having an electron-donating group on the
      methano-bridge carbon.
AB  - A series of novel transformations of [60]fullerene derivatives were found,
      starting from methano[60]fullerenes with an electron-donating group on the
      methano-bridge carbon. Aminomethano[60]fullerenes, in situ generated by the
      treatment of their trifluoromethanesulfonic acid salts with a base, were readily
      converted into 1-acyl-1,2-dihydro[60]fullerenes via the ring opening of the
      cyclopropane moiety. The aldehyde/ketones thus obtained were easily hydrolyzed to
      give 1,2-dihydro[60]fullerene in the presence of hydroxide anions.

PMID- 17451249
TI  - Pt(II)-catalyzed synthesis of 1,2-dihydropyridines from aziridinyl propargylic
      esters.
AB  - Pt(II)-catalyzed cycloisomerization of aziridinyl propargylic esters affords 1,2
      dihydropyridines with regiodefined installation of substituents. A mild
      conversion of the 1,2-dihydropyridines to the corresponding substituted pyridines
      as well as chirality retention from the aziridinyl propargylic ester substrates
      have been demonstrated.

PMID- 17451250
TI  - Effect of molecular structure of phenolic families as hydroxycinnamic acids and
      catechins on their antioxidant effectiveness in minced fish muscle.
AB  - The antioxidant effectiveness of two different families of phenolic compounds,
      hydroxycinnamic acids and catechins, added as a power (0.001% w/w) to chilled
      minced horse mackerel muscle was evaluated. Caffeic acid, chlorogenic acid, o
      coumaric acid, and ferulic acid were selected as hydroxycinnamic acids with
      similar molecular structures. Commercial catechins with different numbers of
      hydroxylic groups, including catechin, gallocatechin, catechin gallate, and
      gallocatechin gallate, were also tested. The effectiveness found was individually
      discussed for each family as a function of the molecular structure. The capacity
      of hydroxycinnamic acids for donating electrons seems to play the most
      significant role for retarding the development of rancidity in fish muscle.
      Conversely, the properties related to the ability for chelating metals and the
      distribution between oily and aqueous phases were not correlated with the
      inhibitory activities. Among hydroxycinnamic acids, the results highlighted the
      potent antioxidant activity of 10 ppm caffeic acid in inhibiting lipid oxidation
      in fish muscle. Its antioxidant efficacy was similar to that of propyl gallate.
      Among catechins, catechin showed the highest antioxidant activity. There was an
      increment of efficacy in fish muscle using concentrations ranging between 10 and
      100 ppm of both caffeic acid and catechin.

PMID- 17451251
TI  - Myowater dynamics and protein secondary structural changes as affected by heating
      rate in three pork qualities: a combined FT-IR microspectroscopic and 1H NMR
      relaxometry study.
AB  - The objective of this study was to investigate the influence of heating rate on
      myowater dynamics and protein secondary structures in three pork qualities by
      proton NMR T2 relaxation and Fourier transform infrared (FT-IR) microspectroscopy
      measurements. Two oven temperatures at 100 degrees C and 200 degrees C
      corresponding to slow and fast heating rates were applied on three pork qualities
      (DFD, PSE, and normal) to an internal center temperature of 65 degrees C. The
      fast heating induced a higher cooking loss, particularly for PSE meat. The water
      proton T21 distribution representing water entrapped within the myofibrillar
      network was influenced by heating rate and meat quality. Fast heating broadened
      the T21 distribution and decreased the relaxation times of the T21 peak position
      for three meat qualities. The changes in T21 relaxation times in meat can be
      interpreted in terms of chemical and diffusive exchange. FT-IR showed that fast
      heating caused a higher gain of random structures and aggregated beta-sheets at
      the expense of native alpha-helixes, and these changes dominate the fast-heating
      induced broadening of T21 distribution and reduction in T21 times. Furthermore,
      of the three meat qualities, PSE meat had the broadest T21 distribution and the
      lowest T21 times for both heating rates, reflecting that the protein aggregation
      of PSE caused by heating is more extensive than those of DFD and normal, which is
      consistent with the IR data. The present study demonstrated that the changes in
      T2 relaxation times of water protons affected by heating rate and raw meat
      quality are well related to the protein secondary structural changes as probed by
      FT-IR microspectroscopy.

PMID- 17451252
TI  - Thermal degradation of antioxidant micronutrients in citrus juice: kinetics and
      newly formed compounds.
AB  - The thermal degradation kinetics of vitamin C, two carotenoids (beta-carotene and
      beta-cryptoxanthin), and hesperidin, as a function of temperature, were
      determined for Citrus juice [Citrus sinensis (L.) Osbeck and Citrus clementina
      Hort. ex Tan]. The influence of dissolved oxygen on the rate of ascorbic acid
      degradation was also assessed. Analysis of kinetic data suggested a first-order
      reaction for the degradation of vitamin C and carotenoids. The kinetics
      parameters Dtheta, z, and Ea have been calculated. Following the Arrhenius
      relationship, the activation energy of ascorbic acid was 35.9 kJ mol-1 and agreed
      with the range of literature reported value. The results on vitamin C and
      carotenoids from citrus juice made it possible to validate the predicting model.
      Thermal degradation of carotenoids revealed differences in stability among the
      main provitamin A carotenoids and between these and other carotenoids belonging
      to the xanthophyll family. The activation energies for the two provitamin A
      carotenoids were 110 and 156 kJ mol-1 for beta-carotene and beta-cryptoxanthin,
      respectively. On the other hand, no degradation of hesperidin was observed during
      thermal treatment. Finally, the vitamin C in citrus juice was not as heat
      sensitive as expected and the main provitamin A carotenoids present in citrus
      juice displayed a relative heat stability. The high-performance liquid
      chromatography-diode array detection-mass spectrometry analysis of degradation
      products showed that the isomerization of the epoxide function in position 5,6
      into a furanoxide function in position 5,8 was a common reaction for several
      xanthophylls. These findings will help determine optimal processing conditions
      for minimizing the degradation of important quality factors such as vitamin C and
      carotenoid in citrus juice.

PMID- 17451253
TI  - Modeling contact angle hysteresis on chemically patterned and superhydrophobic
      surfaces.
AB  - We investigate contact angle hysteresis on chemically patterned and
      superhydrophobic surfaces, as the drop volume is quasistatically increased and
      decreased. We consider both two (cylindrical drops) and three (spherical drops)
      dimensions using analytical and numerical approaches to minimize the free energy
      of the drop. In two dimensions, we find, in agreement with other authors, a slip,
      jump, stick motion of the contact line. In three dimensions, this behavior
      persists, but the position and magnitude of the contact line jumps are sensitive
      to the details of the surface patterning. In two dimensions, we identify
      analytically the advancing and receding contact angles on the different surfaces,
      and we use numerical insights to argue that these provide bounds for the three
      dimensional cases. We present explicit simulations to show that a simple average
      over the disorder is not sufficient to predict the details of the contact angle
      hysteresis and to support an explanation for the low contact angle hysteresis of
      suspended drops on superhydrophobic surfaces.

PMID- 17451254
TI  - Adsorption behavior and cross-linking of EHEC and HM-EHEC at hydrophilic and
      hydrophobic modified surfaces monitored by SPR and QCM-D.
AB  - The adsorption behavior of ethyl(hydroxyethyl) cellulose EHEC and hydrophobically
      modified EHEC (HM-EHEC) at hydrophilic and hydrophobic surfaces has been studied
      using surface plasmon resonance (SPR) and quartz crystal microbalance with
      dissipation monitoring (QCM-D) methods. The adsorbed amounts measured with the
      different methods were different due to large amounts of water in the films. The
      slow adsorption process made it reasonable to assume a continuous polymer
      reconfiguration process at the surface. This was mostly seen for HM-EHEC at the
      hydrophobic surface, where a more flexible structure was adopted during the
      adsorption process. A cross-linking agent was seen to truly interpolymer cross
      link EHEC at the hydrophilic surface and HM-EHEC at the hydrophobic surface. For
      EHEC at a hydrophobic surface and for HM-EHEC at a hydrophilic surface, the
      polymers adsorbed in an individually phase-separated manner, making an
      interpolymer cross-linking reaction unsuccessful.

PMID- 17451255
TI  - Effects of porous polystyrene resin parameters on Candida antarctica lipase B
      adsorption, distribution, and polyester synthesis activity.
AB  - Polystyrene resins with varied particle sizes (35 to 350-600 microm) and pore
      diameters (300-1000 A) were employed to study the effects of immobilization resin
      particle size and pore diameter on Candida antarctica Lipase B (CALB) loading,
      distribution within resins, fraction of active sites, and catalytic properties
      for polyester synthesis. CALB adsorbed rapidly (saturation time </= 4 min) for
      particle sizes </= 120 microm (pore size = 300 A). Infrared microspectroscopy
      showed that CALB forms protein loading fronts regardless of resin particle size
      at similar enzyme loadings ( approximately 8%). From the IR images, the fractions
      of total surface area available to the enzyme are 21, 33, 35, 37, and 88% for
      particle sizes 350-600, 120, 75, 35 microm (pore size 300 A), and 35 microm (pore
      size 1000 A), respectively. Titration with methyl p-nitrophenyl n-hexylphosphate
      (MNPHP) showed that the fraction of active CALB molecules adsorbed onto resins
      was approximately 60%. The fraction of active CALB molecules was invariable as a
      function of resin particle and pore size. At approximately 8% (w/w) CALB loading,
      by increasing the immobilization support pore diameter from 300 to 1000 A, the
      turnover frequency (TOF) of epsilon-caprolactone (epsilon-CL) to polyester
      increased from 12.4 to 28.2 s-1. However, the epsilon-CL conversion rate was not
      influenced by changes in resin particle size. Similar trends were observed for
      condensation polymerizations between 1,8-octanediol and adipic acid. The results
      herein are compared to those obtained with a similar series of methyl
      methacrylate resins, where variations in particle size largely affected CALB
      distribution within resins and catalyst activity for polyester synthesis.

PMID- 17451256
TI  - Microfluidic directed formation of liposomes of controlled size.
AB  - A new method to tailor liposome size and size distribution in a microfluidic
      format is presented. Liposomes are spherical structures formed from lipid
      bilayers that are from tens of nanometers to several micrometers in diameter.
      Liposome size and size distribution are tailored for a particular application and
      are inherently important for in vivo applications such as drug delivery and
      transfection across nuclear membranes in gene therapy. Traditional laboratory
      methods for liposome preparation require postprocessing steps, such as sonication
      or membrane extrusion, to yield formulations of appropriate size. Here we
      describe a method to engineer liposomes of a particular size and size
      distribution by changing the flow conditions in a microfluidic channel, obviating
      the need for postprocessing. A stream of lipids dissolved in alcohol is
      hydrodynamically focused between two sheathed aqueous streams in a microfluidic
      channel. The laminar flow in the microchannel enables controlled diffusive mixing
      at the two liquid interfaces where the lipids self-assemble into vesicles. The
      liposomes formed by this self-assembly process are characterized using asymmetric
      flow field-flow fractionation combined with quasi-elastic light scattering and
      multiangle laser-light scattering. We observe that the vesicle size and size
      distribution are tunable over a mean diameter from 50 to 150 nm by adjusting the
      ratio of the alcohol-to-aqueous volumetric flow rate. We also observe that
      liposome formation depends more strongly on the focused alcohol stream width and
      its diffusive mixing with the aqueous stream than on the sheer forces at the
      solvent-buffer interface.

PMID- 17451257
TI  - Initiated chemical vapor deposition of alternating copolymers of styrene and
      maleic anhydride.
AB  - Initiated chemical vapor deposition (iCVD) of alternating copolymer thin films
      has been achieved for the first time. Copolymerization is desirable for maleic
      anhydride (Ma) since this monomer does not homopolymerize to an appreciable
      extent. At conditions where the observed deposition rates for styrene (S) and Ma
      homopolymers were only 0 and 5.5 nm/min, respectively, combining the two monomers
      resulted in a much higher deposition rate of 75.4 nm/min. iCVD processes utilize
      low energy (<30 W) to generate peroxy radicals from initiator molecules while
      avoiding degradation of functional groups in the monomers. Indeed, full retention
      of the anhydride functionality from the Ma monomer and avoidance of undesirable
      side reactions was observed in iCVD of poly(styrene-alt-maleic anhydride) (PSMa)
      copolymer films. Fourier transform infrared spectroscopy, X-ray photoelectron
      spectroscopy, and 13C nuclear magnetic resonance (NMR) conclusively demonstrate
      that all of the copolymer films contain 50% styrene and 50% Ma (within
      experimental error), irrespective of gas feed ratios employed during the
      deposition. The 13C NMR signal in the 136-140 ppm region from the quaternary
      carbon in styrene and additional distortionless enhancement polarization transfer
      experiments confirmed that the copolymers are strictly alternating. Varying the
      gas feed ratio of Ma to styrene provided control over deposition rates and number
      average molecular weights. Number-average molecular weights varied from 1380 to
      4680 g/mol, and deposition rates varied from 6.3 to 75.4 nm/min.

PMID- 17451258
TI  - Polymer microcapsules with "foamed" membranes.
AB  - This article describes the preparation of capsules displaying craters at their
      surfaces and independent holes inside their membranes. These
      poly(methylmethacrylate) capsules of 20 to 200 microm diameter are prepared by a
      solvent evaporation process and typically contain a dispersant, polyvinyl
      alcohol, and an excipient, namely, a fatty acid triglyceride (miglyol 812).
      Spectroscopic methods showed that, depending on the miglyol content, the craters
      at the surface exhibited sizes of about 1 to 2 microm, whereas the core structure
      of the membrane changed significantly, typically from "soft-part-of-bread" up to
      "foamed"-like aspects. Among several spectroscopy techniques, confocal
      fluorescence microscopy confirmed that the capsules retained the miglyol in their
      core and not in the craters or holes, even after centrifugation and handling.
      This technique also showed that holes in the membrane are filled with water. A
      possible analysis of the "foaming" phenomenon based on the surface tensions of
      different oils, as well as their optimal hydrophile-lipophile balance (HLBO), is
      added to generalize the concept.

PMID- 17451259
TI  - Polyethylene glycol adsorption on silica: from bulk phase behavior to surface
      phase diagram.
AB  - A characterization of the bulk-phase diagram from literature data and new NMR and
      DSC measurements provided us with valuable elements that are helpful for gaining,
      from aqueous solution, better insight into the surface behavior of polyethylene
      glycol on Aerosil 200. Adsorption isotherms built further to measurements by a
      depletion method showed a strong and temperature-dependent variation of the
      isotherm shape in agreement with the variations of interactions already evidenced
      in the bulk. In temperature-concentration areas, where water is behaving as a
      helix-promoting solvent, the finding of positive PEG adsorptions and stairlike
      isotherms agrees with observations reported in the literature. We identified some
      of the vertical parts as corresponding to the formation of monolayers of helix
      shaped PEG molecules. In poor-solvent zones, adsorptions were null or negative,
      and the isotherms exhibited oscillations suggesting very different surface
      behavior. Our data analysis evidenced the presence of a much greater amount of
      water than in the previous surface states; however, the similar analysis of PEG
      behavior remains relevant. Indeed, the occurrence of first-order transitions in
      the surface layer implies some water reorganization, permitting the PEG molecules
      to move closer to the surface and become helix-shaped to rearrange in a
      monolayer. The surface phase diagram confirmed this analysis in a very satisfying
      way.

PMID- 17451260
TI  - Effect of sulfonic acid containing mesogens on liquid-crystalline behavior of
      polysiloxane-based polymers.
AB  - A series of liquid-crystalline polysiloxanes synthesized by cholest-5-en-3-ol
      (3beta)-10-undecenoate and 4'-octanoyloxy-biphenyl-4-yl 4-allyloxy-3-sulfo
      benzoate were prepared in a one-step reaction with sulfonic acid group contents
      ranging between 0 and 2.73 wt %. All the polymers displayed smectic mesophases
      with a large temperature range for the mesophases. With an increase of sulfonic
      acid containing mesogens in the polymers, the temperature of the glass transition
      did not change greatly, while the temperature of the clear point decreased. The
      hydrogen-bonding mesogen aggregates in the domains disturb the liquid-crystalline
      molecular mobility and orientation, leading to a decrease in temperature from the
      mesophase to the isotropic transition. Unlike the polymers containing lower
      sulfonic acid mesogens, some polymers showed a dendritic texture of the SmB*
      phase, indicating that the sulfonic mesogens enhanced the rigid moieties of the
      supermolecular structure of the liquid-crystalline phases. All the polymers
      displayed sharp and strong peaks at low angles around 2theta approximately 2.6
      degrees and broad peaks at wide angles around 2theta approximately 17 degrees in
      X-ray measurements. The intensity of the strong peak at low angles in the X-ray
      profiles decreased with an increase of sulfonic acid mesogens in the polymer
      systems.

PMID- 17451261
TI  - Interaction forces in thin liquid films stabilized by hydrophobically modified
      inulin polymeric surfactant. 3. Influence of electrolyte type on emulsion films.
AB  - The interaction forces in emulsion films stabilized using hydrophobically
      modified inulin (INUTEC SP1) were investigated as a function of concentrations of
      electrolytes of different types (NaCl, Na2SO4, and MgSO4). At a constant
      disjoining pressure of 36 kPa, a constant temperature of 22 degrees C, and a film
      radius of 100 microm, the film thickness, hw, decreased with an increase in
      electrolyte concentration until a critical value, Cel,cr, was reached above which
      hw remained constant. Cel,cr decreased with an increase in electrolyte valency
      (Cel,cr = 5 x 10(-2) mol.dm(-3) for NaCl and 1 x 10(-2) mol.dm(-3) for Na2SO4 and
      MgSO4). The reduction in film thickness below Cel,cr could be accounted for by
      the compression of the electrical double layer. The Pi-hw isotherms below Cel,cr
      could be fitted using the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory
      (constant charge and constant potential cases were considered). At a certain
      pressure, the film jumped to a Newton black film. The pressure at the jump
      decreased with an increase in electrolyte valency as a result of the reduction of
      the electrostatic barrier. At electrolyte (NaCl, Na2SO4, or MgSO4) concentrations
      higher than Cel,cr, the jump occurred at a low pressure that was independent of
      the electrolyte type. The thickness of the Newton black film was independent of
      both the concentration and nature of the electrolytes studied. The results show
      clearly that the polyfructose loops and tails remain strongly hydrated both in
      water and in high concentrations of electrolytes of different types, and these
      results explain the high INUTEC SP1 emulsion stability against coalescence of
      emulsions prepared under such conditions.

PMID- 17451262
TI  - Synthesis of monodisperse biotinylated p(NIPAAm)-coated iron oxide magnetic
      nanoparticles and their bioconjugation to streptavidin.
AB  - We describe here the synthesis of 10 nm, monodisperse, iron oxide nanoparticles
      that we have coated with temperature-sensitive, biotinylated p(NIPAAm) (b
      PNIPAAm). The PNIPAAm was prepared by the reversible addition fragmentation chain
      transfer polymerization (RAFT), and one end was biotinylated with a PEO maleimide
      activated biotin to form a stable thioether linkage. The original synthesized
      iron oxide particles were stabilized with oleic acid. They were dispersed in
      dioxane, and the oleic acid molecules were then reversibly exchanged with a
      mixture of PNIPAAm and b-PNIPAAm at 60 degrees C. The b-PNIPAAm-coated magnetic
      nanoparticles were found to have an average diameter of approximately 15 nm by
      dynamic light scattering and transmission electron microscopy. The ability of the
      biotin terminal groups on the b-PNIPAAm-coated nanoparticles to interact with
      streptavidin was confirmed by fluorescence and surface plasmon resonance. It was
      found that the b-PNIPAAm-coated iron oxide nanoparticles can still bind with high
      affinity to streptavidin in solution or when the streptavidin is immobilized on a
      surface. We have also demonstrated that the binding of the biotin ligands on the
      surface of the temperature-responsive magnetic nanoparticles to streptavidin can
      be turned on and off as a function of temperature.

PMID- 17451263
TI  - Reversible attachment of perylenediimide fluorophore to glass surfaces via strong
      hydrogen-bonding.
AB  - Chemical immobilization of a triethoxysilyl-functionalized hydrogen-bonding
      ureido-[2-(4-pyrimidone)] tetraplex produced interaction sites on a glass
      substrate that allowed association with a perylenediimide-functionalized
      tetraplex, providing noncovalent links of the fluorophore to the surface. The
      association between the self-complementary molecules was exceptionally strong,
      both in solution and at the surface, such that effective hydrogen-bonding was
      retained after repeated solvent washes.

PMID- 17451264
TI  - Using nucleation rates to determine the interfacial line tension of symmetric and
      asymmetric lipid bilayer domains.
AB  - This work presents a novel method for experimentally quantifying interfacial line
      tension, which can be readily applied to study a wide variety of different lipid
      mixtures exhibiting phase coexistence. The method combines AFM imaging of lipid
      domain nucleation with classical nucleation theories. The results, using
      symmetric and asymmetric domains, permit the prediction of key physical
      parameters (critical nuclei size and nucleation rate) in multicomponent bilayer
      systems with implications toward understanding the dynamic nature of
      submicrometer domains (i.e., lipid rafts) in cell membranes.

PMID- 17451265
TI  - S100A8 is identified as a biomarker of HPV18-infected oral squamous cell
      carcinomas by suppression subtraction hybridization, clinical proteomics
      analysis, and immunohistochemistry staining.
AB  - The purpose of this work is to differentiate between the Human papillomaviruses
      18 positive (HPV18+) and negative (HPV18-) oral squamous cell carcinomas (OSCC)
      in oral cancer patients with cancer-associated oral habits (betel quid chewing,
      cigarette smoking, and alcohol drinking). Both gene and protein expression
      profiles of HPV18+ and HPV18- OSCC were compared: we then further explored the
      biological effect of HPV in oral cancer. Suppression subtraction hybridization
      (SSH), clinical proteomics analysis, and immunohistochemistry (IHC) staining were
      carried out in the HPV18+ and HPV18- OSCC groups. HPV typing detection revealed
      that 11 OSCC tissues from 82 patients were positive for HPV18. The SSH experiment
      showed that 4 cancer-associated genes were highly transcribed within 11 cDNA
      libraries of HPV18+ OSCC, including poly(ADP-ribose)polymerase I (PARP1),
      replication protein A2 (RPA2), S100A8, and S100A2. Clinical proteomics analysis
      indicated that there was over 10-fold overexpression of Stratifin, F-actin
      capping protein alpha-1 subunit (CapZ alpha-1), Apolipoprotein A-1 (ApoA-1), Heat
      shock protein 27 (HSP27), Arginase-1, p16INK4A, and S100 calcium-binding protein
      A8 (S100A8) in HPV18+ OSCC. Interestingly, the results from SSH and protemics
      analysis showed that S100A8 was overexpressed in HPV18+ OSCC. Moreover, IHC
      staining demonstrated that S100A8 was up-regulated in HPV18+ OSCC tissues. Our
      results suggest that S100A8 plays an important role in oral carcinogenesis
      following HPV18 infection; therefore, S100A8 may be a powerful biomarker of HPV18
      as well as a potential therapeutic target for HPV18+ OSCC patients. The study is
      the first to identify S100A8 as a biomarker in HPV-associated cancer.
      Furthermore, this is also the first study to discover a biomarker by combining
      SSH, clinical proteomics, and IHC stain analysis in oral cancer-associated
      research.

PMID- 17451266
TI  - Experimental study of the ferroelastic phase transition in urea/n-heptadecane
      composite.
AB  - An experimental study of the ferroelastic phase transition in urea/n-heptadecane
      CO(NH2)2/C17H40 composite around the structural phase transition undergone by
      this crystal at 159 K is presented. The temperature dependence of the macroscopic
      spontaneous strain and the optical birefringence around this temperature has been
      determined. A phenomenological model limited to the hexagonal-orthorhombic change
      of the urea sublattice leads to a linear relation between these quantities and
      the phase transition entropy. The experimental data agree with this description
      exception made of the near vicinity of the phase transition, where the influence
      of the alkane chain ordering processes cannot be excluded.

PMID- 17451267
TI  - Ultrafast excited-state isomerization dynamics of 1,1'-diethyl-2,2'-cyanine
      studied by four-wave mixing spectroscopy.
AB  - Excited-state dynamics and solvent-solute interactions of 1,1'-diethyl-2,2'
      cyanine iodine (1122C) in alcoholic solutions are investigated using time
      integrated three-pulse photon-echo spectroscopy. 1122C serves as a model compound
      for ultrafast photoinduced isomerization-a key process in the light reception of
      plants, bacteria, and human vision. The photoreaction in 1122C is interrogated in
      dependence on solvent and excitation wavelength. The wavelength-dependent three
      pulse photon-echo peak shift indicates strong alterations of the reaction
      pathways and points to the existence of a direct internal conversion channel in
      close proximity to the Franck-Condon point of absorption. The solvent-dependent
      S1-S0 internal conversion time does not follow conventional sheared viscosity
      dependence, suggesting that the solvent local friction has to be considered to
      account for the observed isomerization kinetics. The concerted discussion of
      transient grating and three-pulse photon-echo peak-shift data allows us to derive
      a complete picture of the solvent-solute interaction-controlled photoreaction.
      The results obtained are related to other work on reactive systems and are
      discussed in the framework of multilevel response functions.

PMID- 17451268
TI  - Observation of three behaviors in confined liquid water within a nanopool hosting
      proton-transfer reactions.
AB  - In this contribution, we report on studies of rotational and diffusional dynamics
      of 7-hydroxyquinoline (7HQ) within a reverse micelle (RM) containing different
      amounts of water. Analyzed in terms of the wobbling-in-a-cone model, the data
      reveal structural and dynamical properties of the nanopool. We clearly observed
      three regions in the behavior of confined water molecules within the RM hosting a
      double proton-transfer reaction between the probe and water. This observation
      remarkably reproduces the change of calculated water density within this life
      mimicking medium. The number of water molecules per AOT head in the transition
      regions changes from 2 to 5, the latter being very near to the full solvation
      number (6) of the RM heads. Moreover, the H-bonds breaking and making within the
      RM to give new structures of the probe strongly affect the environment
      fluidization in different extents, reflected in different relaxation times of
      these structures; however, they are of similar sizes. We discuss the role of RM
      confinement and the proton-transfer dynamics on the behavior of water and their
      relationships to the packing of water molecules in the studied range of
      concentrations.

PMID- 17451269
TI  - NaOH concentration effect on the oriented attachment growth kinetics of ZnS.
AB  - In this work, the crystal growth kinetics of ZnS nanoparticles coarsened under
      100 degrees C with NaOH concentration from 2 to 8 M was investigated, aiming to
      study the role of NaOH concentration on the oriented attachment growth kinetics.
      It reveals that 2 M NaOH is sufficient to lead to two-stage growth kinetics of
      ZnS nanoparticles, resulting in pure and multistep oriented attachment growth
      characteristics in the first stage. When the NaOH concentration increases, the
      rate of crystal growth by oriented attachment mechanism increases, while the time
      period for crystal growth at the pure oriented attachment stage was similar. We
      suggest that the concentration of solute is critical to enhance the oriented
      attachment growth rate and achieve exclusively oriented attachment growth of
      nanoparticles at a large size scale.

PMID- 17451270
TI  - Relaxation effect on the Onsager coefficients of mixed strong electrolytes in the
      mean spherical approximation.
AB  - The Fuoss-Onsager continuity equations are solved by using the equilibrium pair
      distribution functions of the mean spherical approximation in the case of equal
      diameters. An analytical expression is obtained for the relaxation effect on the
      Onsager coefficients of mixed strong electrolytes. This work also extends the
      existing expressions for the conductivity of binary and ternary electrolytes to
      any number of ions.

PMID- 17451272
TI  - Indolizidine alkaloids with delta-opioid receptor binding affinity from the
      leaves of Elaeocarpus fuscoides.
AB  - In the first chemical investigation of the Papua New Guinean plant Elaeocarpus
      fuscoides, one new indolizidine alkaloid, elaeocarpenine (1), and three known
      alkaloids, isoelaeocarpicine (2), isoelaeocarpine (3), and elaeocarpine (4), were
      isolated from the leaves. Their structures were determined by 1D and 2D NMR
      spectroscopy. Since treatment of elaeocarpenine (1) with ammonia produced a 1:1
      mixture of the diastereomers 3 and 4, we propose that elaeocarpenine (1) is the
      biogenetic precursor of isoelaeocarpine (3) and elaeocarpine (4). Compounds 1-4
      demonstrated binding affinity for the human delta-opioid receptor with IC50
      values of 2.7, 35.1, 13.6, and 86.4 microM, respectively.

PMID- 17451273
TI  - Ionization and tautomerization of 2-nitrocyclohexanone in aqueous solution.
AB  - The keto-enol tautomerism of 2-nitrocyclohexanone (2-NCH) was studied in aqueous
      solution under different experimental conditions. Ketonization rate constants
      were measured spectrophotometrically at 25 degrees C at an ionic strength of 0.4
      mol dm-3 (NaCl) in diluted hydrochloric acid, in diluted sodium hydroxide, and in
      several buffers by using NaHSO3 as the scavenger of the keto form. A value of
      pK(a)(EH) = 4.78 for the enol form was obtained from the rate-pH profile of the
      reaction. A value of pK(a)(KH) = 5.97 for the keto form was directly obtained
      from the UV-vis spectra of 2-NCH recorded at different pHs. The equilibrium
      constant for the keto-enol tautomerism, pK(T) = -log([enol]/[ketone]) = 1.19, was
      obtained by combining the two pKa values (pK(T) = pK(a)(KH) - pK(a)(EH)). A
      comparison of these results with the corresponding values (Keefe, J. R.; Kresge,
      A. J. In The Chemistry of Enols; Rappoport, Z., Ed.; Wiley & Sons: New York,
      1990; pp 399-480) for cyclohexanone shows the dramatic effects of an alpha-nitro
      substituent on the keto-enol acidities and the tautomerization constant of
      alicyclic ketones. Rates and equilibria were discussed in the light of the
      Bronsted equation, the principle of nonperfect synchronization, and the Marcus
      theory. It turns out that, on passing from nitroalkanes to nitroketones, the
      resonance contribution to pKa and deprotonation rate decreases, being overwhelmed
      by steric and inductive effects.

PMID- 17451274
TI  - Total synthesis of (-)-stemoamide.
AB  - A stereocontrolled total synthesis of (-)-stemoamide (1) is presented. The
      synthesis starts from commercially available (S)-pyroglutaminol (4). A
      chemoselective iodoboration of 5 was used to access key intermediate 3. The
      beta,gamma-unsaturated azepine derivative 2 was obtained via a Pd(0)-catalyzed
      sp(2)-sp(3) Negishi cross-coupling using a Reformatsky nucleophile followed by a
      ring-closing metathesis reaction. The required C8-C9 trans-stereochemistry of 1
      was accessed through a stereoselective bromolactonization/1,4-reduction sequence.

PMID- 17451275
TI  - Microwave-assisted synthesis in water as solvent.

PMID- 17451276
TI  - Direct observation of nanomechanical properties of chromatin in living cells.
AB  - Precise manipulation of nanometer-sized magnetic particles using magnetic
      tweezers has yielded insights into the rheology of the cell cytoplasm. We present
      first results using this approach to study the nanomechanics of the cell nucleus.
      Using a custom-designed micro-magnetic-tweezers instrument, we can achieve
      sufficiently high magnetic forces enabling the application and measurement of
      controlled distortion of the internal nuclear structure on the nanometer scale.
      We precisely measure the elasticity and viscosity inside the nucleus of living
      HeLa cells. The high value of the Young's modulus (Y = 2.5 x 10(2) Pa) measured
      relative to the cytoplasm is explained by a large-scale model for in vivo
      chromatin structure using a polymer network model.

PMID- 17451277
TI  - Successful differentiation of mouse neural stem cells on layer-by-layer assembled
      single-walled carbon nanotube composite.
AB  - The same properties that made carbon nanotube (CNT) composites interesting for
      electronics, sensing, and ultrastrong structural materials also make them an
      asset for biomedical engineering. The combination of electron conductivity,
      corrosion resistance, and strength are essential for neuroprosthetic devices. All
      of the studies in this area demonstrating cellular adhesion and signal
      transduction activity on CNT matrixes were conducted, so far, with terminally
      differentiated primary cells and cancerous cell lines. Neural stem cells are very
      plastic neural precursors capable of adapting to environmental conditions and
      recreating signal transduction pathways. Their intrinsic biological functionality
      not only makes the transition to stem cell cultures a difficult-to-avoid step but
      also implies several fundamentally important challenges. Here we demonstrate that
      mouse embryonic neural stem cells (NSCs) from the cortex can be successfully
      differentiated to neurons, astrocytes, and oligodendrocytes with clear formation
      of neurites on layer-by-layer (LBL) assembled single-walled carbon nanotube
      (SWNT)-polyelectrolyte multilayer thin films. Biocompatibility, neurite
      outgrowth, and expression of neural markers were similar to those differentiated
      on poly-L-ornithine (PLO), one of the most widely used growth substratums for
      neural stem cells.

PMID- 17451279
TI  - Biphasic insulin aspart in type 2 diabetes mellitus: an evidence-based medicine
      review.
AB  - The efficacy benefits of biphasic insulin aspart formulation (BIAsp 30) in
      patients with diabetes mellitus have been reported in several studies. BIAsp 30
      has been shown to be more effective in terms of glycaemic control than standard
      biphasic human insulin 30 (BHI 30). In addition to gauging the treatment in terms
      of clinical evidence of benefits provided, it is also important to evaluate the
      strength of the evidence supporting the therapeutic improvements offered by BIAsp
      30. In this paper, we evaluated the strength of the available data that relate to
      the use of BIAsp 30 in the treatment of patients with type 2 diabetes based on a
      comprehensive literature review. Selected publications that provided relevant
      data were obtained via a literature search and from the manufacturer, Novo
      Nordisk. These were graded in terms of the strength of the evidence they provided
      using the Oxford Centre for Evidence-Based Medicine (CEBM) system in the
      following categories: (i) twice-daily use versus basal insulin; (ii) twice-daily
      use versus other treatments; (iii) once-daily use; (iv) thrice-daily use; (v) use
      in combination with thiazolidinediones; and (vi) use in comparison with BHI 30. A
      total of 30 publications for BIAsp 30 were identified and graded. For the
      majority of categories (four out of six), the evidence supporting the use of
      BIAsp 30 was given an overall CEBM grade of A (highest quality); evidence
      supporting clinical efficacy in the other two categories (twice-daily use versus
      basal insulin and thrice-daily BIAsp 30 administration) was graded B. In most of
      the studies examined, the efficacy of BIAsp 30 was evaluated in terms of
      glycaemic control (glycosylated haemoglobin [HbA(1c)] reduction, proportion of
      patients achieving HbA(1c) target of <6.5% or <7%, fasting blood glucose, blood
      glucose profile and/or prandial and postprandial glucose increments). In some
      studies, efficacy was further evaluated using plasma insulin and glucose infusion
      rates, plasma C-peptide levels, mean serum fructosamine levels, postprandial
      hyperlipidaemia, overall well-being, treatment satisfaction and quality of life.
      Safety was evaluated using physical and laboratory investigations and assessment
      of incidence of adverse events, including, in many of the studies reviewed,
      specific evaluation of those events known to be associated with antidiabetic
      treatment, hypoglycaemia and weight gain. Strong evidence was provided for better
      glycaemic control with BIAsp 30 without increases in the incidence of major
      hypoglycaemia or nocturnal hypoglycaemic episodes. Overall, weight gain with
      BIAsp 30 was minimal and not significantly greater than with basal insulin or BHI
      30. Thus, we can confirm that the reported efficacy and tolerability of BIAsp 30
      in the treatment of diabetes based on a variety of clinical endpoints is
      supported by a good body of evidence relating to its use in different dosage
      regimens and in comparison with other insulin treatment regimens.

PMID- 17451280
TI  - Role of lormetazepam in the treatment of insomnia in the elderly.
AB  - BACKGROUND AND OBJECTIVE: Sleep architecture changes with age, both in terms of
      efficiency and total duration of sleep. Hypnotic benzodiazepines promote rapid
      onset of sleep, uninterrupted sleep and longer duration of sleep in the absence
      of carryover sedation the following morning; therefore, these may be appropriate
      for use in older patients. This study was performed to evaluate the efficacy and
      safety of lormetazepam in elderly patients with primary insomnia when used in
      association with sleep hygiene training (SHT). The impact of restored sleep on
      daily sleepiness was also investigated. PATIENTS AND METHODS: In this open-label
      study, 30 elderly outpatients with insomnia were randomised to receive 2 weeks of
      treatment with lormetazepam 0.5mg + SHT or SHT alone, followed by a 1-week
      observation period. Details on sleep latency, number of awakenings and freshness
      on awakening were recorded by patients in a daily sleep diary. The Epworth
      Sleepiness Scale (ESS) and Stanford Sleepiness Scale (SSS) were used to measure
      daily sleepiness. RESULTS: Addition of lormetazepam to SHT improved all sleep
      parameters measured compared with SHT alone. Mean duration of sleep improved
      significantly from baseline (mean rank=1.00) in the lormetazepam + SHT group
      after 2 weeks of treatment (mean rank 2.87; Friedmann test=27.448; p<0.001), but
      declined significantly in the group receiving SHT alone (from mean rank 2.33 to
      1.57; Friedmann test=6.465; p<0.05). Mean duration of sleep increased by
      approximately 150 minutes each night in the lormetazepam + SHT group but
      decreased by more than 30 minutes in the SHT-only group. Improvement in sleep
      quality from baseline was statistically significant only in the lormetazepam +
      SHT group: for both deepness of sleep and the perception of awakening refreshed,
      mean scores increased from approximately 3 at baseline to approximately 8 (on a
      scale of 1-10) after 2 weeks in this group. Sleep latency also decreased
      significantly in the lormetazepam + SHT group: after 2 weeks, on average patients
      were awakening less than once per night. SSS and ESS scores also improved
      significantly in the lormetazepam + SHT group; in contrast, in the SHT-only
      group, the mean ESS score worsened significantly from baseline and the mean SSS
      score remained relatively constant. No rebound insomnia was reported during
      follow-up in patients in the lormetazepam group. Vital signs did not change from
      baseline and no adverse events were reported for either group. CONCLUSION:
      Management of insomnia in the elderly appears to have a better outcome when
      pharmacotherapy is combined with SHT rather than SHT alone. The earlier
      improvement in sleep quality with lormetazepam when used in combination with a
      sleep training programme may help to maintain adherence to treatment.

PMID- 17451281
TI  - Effectiveness and safety of ezetimibe added to statin therapy in patients with
      primary dyslipidaemia not achieving the LDL-C treatment goal on statin
      monotherapy.
AB  - BACKGROUND AND OBJECTIVE: Elevated serum low-density lipoprotein cholesterol (LDL
      C) is a major cardiovascular risk factor. This study aimed to determine the
      efficacy and safety of co-administration of the cholesterol absorption inhibitor
      ezetimibe with an HMG-CoA reductase inhibitor (statin) in the treatment of
      Mexican patients with dyslipidaemia who had not attained the LDL-C treatment goal
      with statin monotherapy. MATERIAL AND METHODS: We studied 256 patients with
      elevated serum LDL-C (as defined by the US National Cholesterol Education Program
      Adult Treatment Panel III guidelines) despite statin therapy. All patients had
      lipid profiles performed at baseline and after 6-8 weeks of treatment with statin
      therapy plus ezetimibe 10 mg/day for 6-8 weeks. RESULTS: Addition of ezetimibe to
      statin treatment reduced mean serum LDL-C levels significantly (from 160 +/- 42.8
      to 100 +/- 36 mg/dL; p<0.001) after 6-8 weeks of treatment, with 61.7% of
      patients achieving LDL-C values below the goal established according to their
      coronary risk group. Serum LDL-C goals were achieved at the end of the study in
      88.2% of the low-risk coronary group, 75.7% of the moderate-risk group and 47.8%
      of the high-risk group. Ezetimibe was well tolerated; no hepatic or muscle
      related adverse events were observed. CONCLUSION: Addition of ezetimibe to statin
      treatment was both efficacious and safe when used for further reduction of serum
      LDL-C in dyslipidaemic patients who had not reached their LDL-C treatment goal
      while taking statin monotherapy.

PMID- 17451282
TI  - The real-life safety and efficacy of vardenafil: an international post-marketing
      surveillance study of 2824 patients from the Middle East.
AB  - OBJECTIVE: To assess the safety, efficacy and patient acceptability of vardenafil
      treatment under real-life conditions in patients with erectile dysfunction (ED).
      METHODS: The present publication shows the results of a subgroup analysis of a
      multinational post-marketing surveillance study, including 2824 Middle East
      patients with ED whose attending physician chose vardenafil as the most
      appropriate therapy. Patients were assessed at an initial visit for demographic
      and baseline characteristics. At one or two follow-up visits, covering a period
      of approximately 2 months or eight vardenafil intakes, patients were interviewed
      about overall treatment success (general improvement of erection, number of
      tablets taken until improvement, patient's satisfaction with overall efficacy and
      tolerability, comparison with last ED treatment). All adverse events were
      recorded and assessed for a possible relationship to treatment, and for severity.
      RESULTS: An overall improvement in erections was reported in 94.3% of patients.
      Most patients achieved treatment success after the first (67.0%) or second (83.6%
      cumulative) tablet. Diabetic patients had a similar improvement rate (92.2%) and
      73.5% of patients who had undergone radical prostatectomy reported an overall
      improvement. The rate of adverse drug reactions (ADRs) was low (9.1% of
      patients). The most common ADRs were headache (5.8%), flushing (1.6%), nasal
      congestion (1.0%), dyspepsia (0.6%) and nausea (0.5%). In total, 88.9% of
      patients wanted to continue treatment with vardenafil. CONCLUSION: Vardenafil was
      effective, reliable and well tolerated in patients with ED treated under real
      life conditions.

PMID- 17451283
TI  - Impact of losartan on stroke risk in hypertensive patients in primary care.
AB  - BACKGROUND AND OBJECTIVE: While a number of conditions and risk factors that
      increase stroke risk have been identified, arterial hypertension is the most
      consistent and powerful predictor. The angiotensin II type 1 receptor antagonist
      (angio-tensin receptor blocker [ARB]) losartan has been shown in the LIFE
      (Losartan Intervention for Endpoint Reduction in Hypertension) study to decrease
      stroke risk in hypertensive patients to a substantially greater extent than
      conventional therapy. We aimed to assess the impact of the blood pressure
      lowering effect of losartan therapy on stroke risk in hypertensive patients in
      primary care. METHODS: A total of 2977 primary-care practices throughout Germany
      included 22 499 consecutive unselected patients with a confirmed diagnosis of
      hypertension in an open-label, prospective, observational study. In addition to
      demographics, known risk factors for stroke were documented on standardised
      questionnaires. The 10-year predicted risk of first stroke was calculated
      according to the Framingham Stroke Risk Score at baseline and after a mean of 94
      +/- 24 days of losartan (+/- hydrochlorothiazide [HCTZ]) therapy. RESULTS: The
      mean patient age was 64.1 +/- 10.6 years, and 52.4% were males. Mean
      systolic/diastolic blood pressure decreased from 160 +/- 15/93 +/- 9 mm Hg at
      baseline by -21 +/- 14/-11 +/- 9 mm Hg. Besides hypertension, 84.9% of patients
      had other co-morbidities, of which the most frequent were hypercholesterolaemia
      (53.0%), diabetes mellitus (36.1%), coronary heart disease (31.1%) and left
      ventricular hypertrophy (24.2%). The average predicted 10-year stroke risk was
      28.0 +/- 21.9% at baseline, and 22.1 +/- 19.5% at study end (relative risk
      reduction 24 +/- 16%, p<0.05). In subgroups of patients with diabetes or
      nephropathy, similar effects were noted. Drug-related adverse events were
      reported in 18 patients; all of these were non-serious. CONCLUSION: Because of
      the high prevalence of co-morbidities and risk factors, the hypertensive patient
      population observed in this study presented with a high 10-year stroke risk.
      Treatment with losartan (+/- HCTZ) was well tolerated and led to a substantial
      decrease in blood pressure and associated stroke risk.

PMID- 17451284
TI  - Low-molecular-weight heparins: before or after surgery? New concepts and
      evidence: Congress report from the Sigma Tau/ROVI Satellite Symposium (Rome,
      Italy, 13 November 2006).
AB  - Deep venous thrombosis (DVT) and pulmonary embolism (PE) are potentially life
      threatening complications associated with orthopaedic surgery. The choice of an
      optimal thromboprophylaxis regimen requires full understanding of the efficacy
      and safety profiles associated with distinct treatments. Low-molecular-weight
      heparins (LMWHs) are the drugs of choice for thromboprophylaxis in orthopaedic
      surgery. However, there is concern regarding the timing of LMWH prophylaxis
      initiation. Among the LMWH molecules, bemiparin has interesting pharmacological
      properties: the lowest molecular weight, the longest half-life and the highest
      anti-FXa/anti-FIIa activity ratio. The safety and efficacy of bemiparin
      administered 6 hours after surgery has been demonstrated in several orthopaedic
      settings (including major orthopaedic surgery, knee arthroscopy, lower limb
      trauma and spinal surgery) and during prolonged prophylaxis after major
      orthopaedic surgery. Another factor to consider in relation to thromboprophylaxis
      during orthopaedic surgery is the cost effectiveness of bemiparin. The 91st
      meeting of the Italian Society of Orthopaedics and Traumatology (SIOT), held in
      Rome, Italy, on 12-16 November 2006, provided an exciting opportunity to present
      new and interesting evidence, including the latest advances in thromboprophylaxis
      in orthopaedic surgery. Of particular interest were the issues debated during the
      Sigma Tau/ROVI Satellite Symposium, which focused on the optimal timing strategy
      for initiating thromboprophylaxis in patients undergoing orthopaedic surgery.
      This article highlights presentations given during that symposium.

PMID- 17451285
TI  - The need for good practices in biomedical technology.
AB  - The present modern technologies have made it possible for one to carry out
      intricate and highly sensitive procedures that in the past were impossible or
      unheard of. The pharmaceutical industry has provided sophisticated products with
      unique drug delivery systems. Instrumentation technology has made it possible for
      the production of machines and facilities for use in the diagnosis and management
      of disease. Clinical science has reached such high levels of achievement as to
      enable an efficient patient management. Scientists and professionals working in
      these fields have thus been provided with modern tools with which to provide more
      efficient service to mankind. But consumers having become as equally
      sophisticated as these advancements, also require to know whether these products,
      equipment and services are fail-safe. They demand assurance; as it were, quality
      assurance. Gone are the days when the health professional would maintain his/her
      absolute competence, the pharmacist would assert that the pharmaceutical product
      was perfect, the laboratory analyst would claim that the laboratory results were
      excellent, and the physician would sternly uphold his clinical supremacy. Now, it
      is well known that there are no such ideals in health science research and
      practice. To try to attain the best level possible, professional bodies all over
      the world have established guidelines for Quality Assurance, Accreditation and
      Certification. The International standards Organization (ISO) has formulated
      comprehensive standards for all forms of quality audit and certification. The
      five quality management standards of the ISO, known as ISO 9000, ISO 9001, ISO
      9002, ISO 9003, and ISO 9004, have been adopted by many organizations in various
      countries of the world. The principles of Good Laboratory Practices (LP) which
      were initially formulated by the Food and Drug Administration (FDA) of the USA
      was adopted by the European Union (EU) in 1989. The World Health Organization
      (WHO) has also issued Guidelines for Good Clinical Practice (GCP), Guidelines for
      Good Manufacturing Practices (GMP) of Pharmaceuticals, and Guidelines for the
      Production of Biologicals. It is thus evident that quality assurance is a very
      important aspect in all fields of health science research and practice. Quality
      assurance embraces quality control and audit and involves three things: personnel
      and material resources, quality system structure, and management
      responsibilities. Well trained personnel are required to use the appropriate
      materials and tools, an efficient quality system structure is desirable, and a
      good management system to implement the quality assurance programme is very
      essential. This programme should also enable the providers of goods and services
      to be bold enough to disclose to the consumers when their goods and services
      fail, as in the recent case of Abbot Laboratories when they had to withdraw their
      HIV test kit from the market after failing to meet the prescribed standards.
      Similarly, some years ago the anti-inflammatory drug Benoxaprofen (ORAFLEX-Eli
      Lilly) was withdrawn shortly after its introduction in the clinic. Do the
      organisations in Africa have the capacity to develop, or adopt, a quality
      assurance programme? It is fair to answer in the affirmative Organisations in
      Africa can, and should, adopt any of the existing quality assurance programmes
      that suit their operations best. What is most important is that operations must
      have the means to establish specificity, accuracy, precision and sensitivity that
      can be verified and certified. The big question is, do all these nicely worded
      standards, guidelines and practices have uniform and enforceable laws that enable
      their effective implementation and protection of the consumers?

PMID- 17451286
TI  - The role of biological response modifiers on apoptosis in HIV infections and
      AIDS.
AB  - The vital role played by biological response modifiers especially interferon
      alpha (IFN) in HIV infections and AIDS is discussed. Apoptosis, a phenomenon of a
      genetically controlled physiological cell death is also discussed in relation to
      HIV infections and its response to oropharyngeal IFN therapy. HIV infections
      induce apoptosis at a stage when CD4-positive T lymphocytes are still immature
      and weakly expressing CD4 molecules. During IFN therapy, the process of apoptosis
      is blocked or down-regulated, thus rendering the immature cells to rapidly mature
      to strongly express CD4 molecules and to perform their expected functional role.
      These observations are of critical importance in further understanding of the
      salient features associated with HIV/AIDS, and which may be exploited in the
      design of strategic intervention measures.

PMID- 17451287
TI  - Problems and solutions associated with transmission of HIV via donated blood in
      Tanzania.
AB  - Donor-blood from populations with high prevalence of HIV infection carry the risk
      of transmitting HIV to a significant proportion of recipients. This paper
      presents a review of experience gained in efforts towards ensuring availability
      of HIV-free blood for transfusion in tropical Africa, with emphasis on Tanzania.
      The effect of introducing a countrywide screening programme in averting possible
      HIV transmission, and the main problems of controlling transfusion associated
      with HIV infection have been identified. Lack of organized blood transfusion
      services in tropical Africa, widespread occurrence of transfusion associated
      diseases, shortage of skilled staff, unreliable electricity supply and
      communication networks, and absence of a 100% sensitive antibody test for HIV are
      among the problems encountered in attempts to provide safe blood. To reduce
      transfusion associated HIV infection, efforts should be directed to; reduction of
      unnecessary blood transfusions; exclusion of HIV high-risk donors, provision of
      affordable, rapid and reliable HIV antibody test kits, using heat-treated and HIV
      free blood products for treatment of bleeding disorders; and establishment of
      separate facilities fur voluntary HIV testing and counselling form blood donation
      centers. With continuing successes globally in the development of simple, rapid,
      affordable and highly sensitive HIV antibody tests, the control of HIV
      transmission through blood transfusion should be feasible in all areas of Africa.

PMID- 17451288
TI  - Oesophageal and other cancer patterns in four selected districts of the Transkei,
      Southern Africa:1985-1990.
AB  - New data regarding the incidence of oesophageal and other cancers during the
      period 1985-1990 are reported for all clinics and hospitals in four selected
      districts of Transkei, Southern Africa i.e. Kentani, Butterworth, Lusikisiki and
      Bisana. Active and passive methods were used to obtain the hospital-based cancer
      registry data. The mean annual number of cancer cases recorded for the period
      1985-1990 was 292. Age-standardised incidence rates (ASIR, African standard) for
      all recorded cancer were 81.4 and 52.6/100,000 for males and females
      respectively. Histopathological examination of 52.6% of recorded tumors revealed
      that 67.3% were squamous carcinomas, 21.7% adenocarcinomas and the remainder non
      epithelial neoplasm. Cancer of the oesophagus (OC) was the most frequently
      recorded cancer and accounted for the 46.5% of the cases with mean ASIR of 46.7
      and 19.2/100,000 for males and females respectively. The male/female ratio was
      2.4:1. The highest mean ASIR per annum for OC in males (55.6/100,000) occurred in
      Kentani and in females (22.3/100,000) in Lusikisiki, whereas the lowest rates in
      both sexes (37.0 and 11.7/100,000 respectively) occurred in Bizana. Comparison of
      the OC rates in the four districts of Transkei during 19985-1990 with previous
      reported trends, confirms a consistently high rate in the south-western districts
      of Kentani during the past 35 years and progressively increasing rates in the
      north-eastern districts of Bizana and Lusikisiki. These results have profound
      implications for further epidemiological and aetiological studies on OC in
      Transkei, but we need to be corroborated by data form other sources such as
      statistics on histologically diagnosed cancer in Transkei by districts in the
      South African National Cancer Registry. The second most frequent recorded cancer
      among males was liver cancer with a mean annual ASIR of 6.0/ 100,000 and
      male:female ratio of 3:1. The most frequent recorded cancer among females was
      cervical cancer with a mean annual ASIR of 20.9/100,000 followed by OC
      (19.2/100,000) and breast cancer (5.8/100,000).

PMID- 17451289
TI  - Pulmonary function results in asbestos factory workers.
AB  - The pattern of lung function was assessed in a group of 159 male employees of the
      Dar es Salaam asbestos factory. The results were compared with a control group
      (N= 180) of age and sex matched from the same area but not exposed to asbestos.
      The mean age were 32.8, SD=8.9 and 33.1 SD=7.7 years in the asbestos workers and
      control groups respectively. Lung function indices showed an increase with age
      reaching peak values between 30-34 years of age. FVC and FEV(1) values were
      similar in the two groups. However, MMEF, PEF, V(75), V(50), and V(25) were
      significantly lower in asbestos factor workers than in the control group.
      Observed results were also compared with results computed from prediction
      equation for normal healthy subjects. Observed FVC and FEV(1) values were similar
      to predicted values while MMEF and PEF values were significantly lower ([P <
      0.05]) and [P < 0.001] respectively) in asbestos factory workers than predicted
      values. The reduced flows suggest early airways dysfunction affecting peripheral
      airways more than large airways, a finding supported by the normal FVC and FEV(1)
      values. It is recommended that efforts should be directed at increasing awareness
      of employees on the risks associated with asbestos and frequent health monitoring
      to all factory workers should be instituted.

PMID- 17451290
TI  - Does chloroquine treatment influence the distribution of pyrimethamine-resistant
      P. falciparum parasites in the field?
AB  - In a limited case controlled but molecular study in symptomatic Tanzanian
      children, we found that those who had not previously received Chroloquine
      treatment had a higher proportion of parasitaemia. There was also a higher
      proportion of pyrimetamine-resistant P. falciparum parasites among those who had
      not received any treatment. This finding is paradoxical and the reasons for this
      observation are suggested.

PMID- 17451291
TI  - Metabolism of Diazepam and Ethosuximide in rats with malaria and endotoxin
      induced fever.
AB  - We have investigated the effects of malaria infection with rodent parasite
      Plasmodium berghei and fever induced by Escherischia coli endotoxin on the
      metabolism of diazepam to temazepam by rat liver microsomes, and on the clearance
      of ethosuximide in vivo in the rat. Livers from malaria-infected (parasitaemia
      =36.8+/- 7.6% endotoxin-treated or saline-treated (control) rats (N=5 per
      treatment) were used to prepare microsomes. These were incubated with diazepam
      (10-600u M) for 10 minutes in an NADPH-generating system. V( max), K(m ) and the
      intrinsic clearance V(max )/K(m ) for the production of temazepam were
      determined. In separate experiments, ethosuximide (5mg/kg) was administered via
      the tail vein to control, malaria-infected and endotoxin-treated rats
      (parasitaemia=43.8+/- 5 %) under light ether anesthesia (N=5 per treatment).
      Total clearance of ethosuximmide was estimated form a single blood sample
      obtained 24h after drug administration. Diazepam metabolism was not affected by
      malaria infection or fever (V(max ):1.31+/- 0.34,0.73+/- 0.27 and 1.07+/- 0.78
      nmol/min/mg protein; K( m): 158.7 +/- 63.7, 175.3+/- 44.9 and 190.0+/- 81.8uM;
      Intrinsic clearance/whole liver: 0.31+/- 0.16, 0.26+/- 0.1 and 0.29+/- 0.1ml/min
      in livers from control, malaria-infected and endotoxin-treated rats respectively;
      P>0.05). Similarly, clearance of ethosuximide in vivo was not affected by malaria
      infection or fever (1.3+/- 0.2, 1.3+/- 0.01 and 1.4+/- 0.4 ml/min/kg in control,
      malaria-infected and endotoxin-treated rats respectively; p>0.05). These results
      suggest that malaria infection and fever have no effect on the activities of the
      CYP3A isozymes thought to be involved in the metabolism of diazepam and
      ethosuximide.

PMID- 17451292
TI  - Emerging and re-emerging Infectious diseases: a global health threat.
AB  - The HIV/AIDS pandemic can truly be described as an infectious disease that has
      recently emerged and judging from its rapid global spread, it leaves no doubt
      that it is one of the greatest health threats mankind has to contend with. This
      pandemic has alerted and stimulated the international scientific community to
      seriously reflect oa other recent episodes of emerging and re-emerging
      infections. The examples that have recently been observed and addressed include
      new emerging infectious diseases, unusual manifestations of previously known
      diseases and unusual eruption of known diseases in unusual geographic foci or
      unusual altitudes. The scientific community has considered the following as
      plausible explanations for the epidemics: 1. It is known that micro-organisms
      mutate and selection pressures for appearance of resistant strains are encouraged
      by the widespread misuse of drugs; 2. Human population pressures, particularly ih
      the developing world, is leading migration to urban slums. Other populations are
      venturing into virgin jungles to open up new agricultural land. In the same
      category are economic pursuits in the forest or alteration of the environment by
      economic activities such as new dams and roads. All these activities put new
      susceptible populations at risk of interacting with new disease ecological
      systems. It is also tempting to include in this category civil disruptions which
      have led to acute displacement of large populations within a country or across
      international borders as refugees; 3. The re-emergence of some of the old
      familiar diseases, hitherto considered well controlled, can be attributed
      directly to the deterioration of health services as a result of global economic
      depression which has affected some countries more severely than others; 4. There
      is sound and growing scientific evidence implicating global warming as
      contributing to some of the new disease manifestations. The threat to health by
      emerging and re-emerging infectious diseases is a reality and the scientific
      basis for this occurrence, though complex, is slowly being understood. The
      response of the international scientific community to this situation has been
      acknowledged as appropriate. It is gratifying to recognise the leading role that
      CDC/US A in collaboration with WHO are playing in globalising the responses to
      these threats. WHO has rightly assumed its leadership role in matters of this
      nature in coordinating global efforts to address this subject. A new division of
      Emerging Infectious Diseases (EMC) became operational in WHO headquarters in
      October 1995. The scientific world looks to it for timely, accurate global
      information, coordination and resource mobilisation. Some of the activities that
      are deemed central in globalising the surveillance for emerging and re-emerging
      diseases are: 1. Setting up of a global network for laboratories capable of
      rapidly identifying emerging and re-emerging organisms; 2. Setting up of a global
      network for surveillance and monitoring the development of antibiotic resistant
      organisms. The WHONET computer programme is already operational in some countries
      and extension of its use to other countries will lead to a very powerful and
      comprehensive global monitoring system for antibiotic resistant organisms. The
      participation of Kenya Medical Research Institute in this programme has been
      elicited as one of the pilots for Africa; 3. Setting up rapid reaction forces to
      respond to specific outbreak situations in order to control the spread of an
      emerging infectious disease. In this area of rapid trans not continental travel,
      the world is viewed as a "global village" and the relevance of the current
      International Sanitary Regulations requires a re-appraisal. Global sensitisation
      of the international community to the importance of this programme will ease and
      facilitate efforts at mobilisation resources needed and the training of the
      manpower required to make the above activities operational on a global scale.

PMID- 17451293
TI  - Immunology of cutaneous and visceral Leishmaniasis: a perspective.
AB  - Visceral and cutaneous Leishmaniasis have been widely recognised as in vitro
      models for the differentia! regulation of CD4+ T cell subsets. These subsets are
      characterised on the basis of partially non-overlapping patterns of cytokine
      production. Thus, Th l type cells produce IL-2 and IFN y, whereas Th 2 cells
      produce IL-4 and IL-5. Both cell types are capable of producing other cytokines
      such as IL-3. The relationship between the functional expression of these
      populations and disease outcome has become a central focus for vaccine design,
      with potentially protective antigen formulations being screened for their ability
      to specifically induce cytokines, characteristic of the host protective reponse.
      Observations such as these are important in designing therapy and vaccines for
      most infectious diseases.

PMID- 17451294
TI  - The roles of IgG and defined antigens in cytoadherence and cytotoxicity reactions
      to onchocercal microfilariae.
AB  - Cytoadherence and cytotoxicity reactions against larval stages of Onchocerca
      volvulus may be protective or pathogenic. To elucidate the inherent mechanisms,
      we examined a panel of human, rabbit and mouse antisera to O. volvulus antigens.
      Human IgG, but not IgM from onchocerciasis sera promoted the adherence of
      leucocytes to microfilariae (mf) that resulted in the killing of the mf in the
      presence of heat labile serum factors. Polyclonal and monoclonal antibodies to
      three recombinant antigens of O. volvulus (OV7I, OV25 and O13) were assayed for
      their abilities to induce cellular adherence and/or cytotoxicity of nodular mf.
      These antibodies were found to promote cytoadherence but showed negligible
      cytotoxicity effects. We conclude that IgG antibodies from onchocerciasis sera
      are implicated in the adherence to and killing of mf by patients' leucocytes.

PMID- 17451295
TI  - Parasitological and clinical studies on Wuchereria bamcrofti infectionin Moyamba
      District, Sierra Leone.
AB  - A total of 302 people were examined in 3 villages in the Moyamba District, Sierra
      Leone of microfilaria (mf) and clinical signs of Wuchereria bancrofti infection.
      Mf rates were 34.5% and 31.8% for Bonganema, Old Mosongo and Pelewahun
      respectively. The average mf rate of those examined was 34.8%. Analysed by age
      and sex, the highest mf rates were observed in males of age >/=21 years (46 -
      56%). The relative risk of infection was significantly lower (P<0.000) for 5-10
      year olds than 11+ year old individuals. Clinical studies of 284 individuals of
      age >/=11 years showed that recurrent fever was the commonest clinical sign
      observed and the rate was 5.9%. For the ages >/=41 years, the recurrent fever was
      10%. The average hydrocele and elephantiasis rates were 2.5% and 1.1%
      respectively. For the ages >/=41 years, the hydrocele and elephantiasis rates
      were 4% and 3% respectively, indicating that Filariasis is an important public
      health problem in the area. Annual mass treatment of the study area residents
      with ivermectin for onchocerciasis has begun. Ivermectin has been reported to be
      effective for control of lymphatic Filariasis. The displacement of the population
      due to the undeclared war in the area will certainly negate the effects of the
      mass treatment programme.

PMID- 17451296
TI  - Glyoxalase-I activity levels in peripheral blood of Ghanaian Africans with or
      without Plasmodium falciparum.
AB  - Glyoxalase-I together with glutathione (GSH) are associated with the maintenance
      of homeo-static level of methylglyoxal. The latter is a metabolite of glycolysis
      and is also formed in various consumable products during food processing.
      Glyoxalase-I is present in the malaria parasite which is common in tropical
      countries worldwide. We thus determined glyoxalase-I activity in the blood of
      Ghanaian Africans and the extent to which malaria parasitemia alters the activity
      of the enzyme in host blood. The data obtained indicate that the presence of
      P.falciparum in peripheral blood has no effect on blood glyoxalase-I activity.
      Mean enzyme activity was 8.5 U/ I (range:2.6-15.2) for controls and 10.6 U/I
      (range 2.7-23.1) for parasitized subjects (parasite density/microl blood 1,200
      64,853; mean:21,863). The blood GSH level was similar between the two groups. A
      biphasic enzyme activity was, however, noted. In 7 (15.9%) of the 44 subjects
      (with or without malaria parasites) the glyoxalase-I activity was low (3.1+/-0.3
      versus 10.8+/- 4.5 U/L) and significant (p < 0.001). Blood GSH level of those
      with decreased enzyme activity was also low (0.41+ 0.03 versus 0.67+/- 0.38
      mmol). This finding suggests that sections of the Ghanaian populace may be less
      efficient in the detoxication of methylglyoxal. The possible implications of this
      on hepatotoxic actions of methylglyoxal are discussed.

PMID- 17451297
TI  - Antimalarial activity of fractions isolated from Albizia gummifera and Aspilia
      mossambicensis crude extracts.
AB  - To identify the fractions of medicinal plant extracts containing the highest
      concentration of antimalarial principles, we tested the antimalarial activities
      of the crude or total extracts and two fractions from Albizia gummifera
      (Leguminosae) and three fractions from Aspilia mossambicencis (Compositae)
      against laboratory adapted isolates of Plasmodium falciparum in vitro using the
      3H-hypoxanthine uptake assay. Chloroquine was used as a reference antimalarial
      drug. The mean 50% inhibitory concentrations (IC50s) of A. gummifera total
      extract and fraction were both <2.2 microg/ml for three P. falciparum isolates
      while the mean IC50 of A. gummifera f raction-2 was higher (5.0+2.9sd) for the
      same isolates. Aspilia mossambicensis total extract and fractions-1,4 and 5 had
      mean IC50 values of 96.6+/-32.5,38.6+/-23.0,142.5+/-79.6 and >1250.0 microg/ml,
      respectively, against four P. falciparum isolates. These results show that
      fraction-1 of either A. gummifera or A, mossambicensis had the highest
      concentration of antimalarial principles. We now plan to concentrate our efforts
      on these promising fractions in order to isolate pure compounds which could
      eventually be used to effectively treat malaria.

PMID- 17451298
TI  - Transmission electron microscopy on simian immunodeficiency virus-infected
      cocultures of vervet monkeys.
AB  - Healthy African green monkeys are the natural reservoirs for certain HIV-related
      SIVs. More research is now focused on these nonhuman primates that are
      asymptomatic, so as to answer questions of origins, pathogenesis and therapy with
      respect to HIV in man. The present study involves the isolation and subsequent co
      cultivation of SIV variants from two healthy vervet monkeys (Cercopithecus
      aethiops pygerythrus). Western Blots (New LAV Blot 1 and New LAV Blot 2, Pasteur)
      revealed sero cross-reactivity of each monkey to major HIV-1 and HIV-2 antigens.
      Freshly isolated peripheral blood mononuclear cells of each monkey were co
      cultivated with the CEMss and M4C8 T-cell lines. The cocultures were incubated in
      CO2 at 37 degrees C for 3-4 days, before refeeding with RPMI 1640,
      phytohaaemagglutinin and interleukin-2. Cytopathic effects in the cocultures were
      observed 14 days post-infection, with syncytia and enlarged, granular cells being
      predominant in both of the cell-lines used. The presence and morphology of viral
      like particles were observed by transmission electron microscopy.
      Immunocytochemistry and in situ hybridization may help in characterization of the
      particles, as well as aid in determining localization and concentration in vitro.

PMID- 17451299
TI  - Detection of HBV-DNA and HCV-RNA viral sequences by polymerase chain reaction in
      selected Kenyan samples and the relationship to HBV seromarkers.
AB  - We undertook a study on selected samples from patients who had presented with
      viral hepatitis and conditions of the liver (liver cirrhosis, chronic hepatitis
      and hepatocellular carcinoma). Diagnosis, screening and confirmation for viral
      hepatitis was done using a battery of techniques: ultrasound, conventional
      serological methods (Hepatitis B surface Antigen [HBsAg] - Reverse Passive
      Haemagglutination [RPHA], Hepatitis B core Antibody [HBcAb] - Passive
      Haemagglutination [PHA], Alpha-feto Protein - RPHA), Hepatitis B e
      Antigen/Antibody [HBeAg/Ab] - Radioimmunoassay [RIA], Hepatitis C antibody [HCV
      Ab] - Enzyme Immunosorbent Assay [EIA]. Due to the high specificity and
      sensitivity of the Polymerase Chain Reaction technique [PCR] in detecting the
      viral genomes, it was used to establish the presence of the HBV-DNA and HCV-RNA
      to correlate the serological diagnosis of their respective seromarkers. A total
      of 39 serum samples were tested comprising 11 blood donors, 8 chronic liver
      disease patients and 20 hepatocellular carcinoma cases. 4/19 (21%) HCV-antibody
      (C-l) reactive samples were found to be positive for HCV-RNA by PCR. 14 of the 19
      (73.7%) including the 4 HCV-RNA positive cases tested positive for HBcAb. 6 of 11
      (55%) HBsAg positive cases also tested positive for HBV-DNA by PCR, In 8 of 20
      (40%) hepatocellular carcinoma cases, no aetiological role could be assigned to
      hepatitis B or C as only HBcAb was demonstrated in those cases.

PMID- 17451300
TI  - Lower limb flexibility norms: some racial, gender and limb symmetrical
      considerations.
AB  - The joint flexibility of the lower limb of 400 undergraduate students (200 males
      and 200 females) whose ages ranged between 20 and 25 years were measured with the
      standard goniometer. The measured range of motion were hip flexion, extension,
      abduction, adduction, medial and laterial rotation, knee flexion and ankle
      dorsiflexionn and plantarflexion. Overall it was found that Nigeria adults
      demonstrated more lower limb joints flexibility than those reported by the
      American Academy of Orthopaedic Surgeons (AAOS) (1963). Females exhibited higher
      flexibility in hip extension, adduction, medial and lateral rotation, ankle
      dorsiflexion and plantarflexion, but were lower in hip flexion and abduction as
      compared to males. For both sexes, only slight asymmetrical variation were
      observed in the joint measurements obtained for the right and left lower limbs.
      Our findings suggested that the application of universal joint flexibility norms
      for different racial groups may be clinically inappropriate. Thus flexibility
      norms may be specific to the racial population from which it was derived. It also
      alerts physical therapists on the need to discriminate joint mobilities between
      male and female patients. It is envisaged that the findings of this study will
      further assist physical therapists while assessing young adult patients who may
      suffer musculoskeletal dysfunction affecting the lower extremity. In treating a
      patient, the unaffected contra-lateral limb joint may validly be used as a
      standard for the affected one.

PMID- 17451301
TI  - Renal vein and intracaval invasion by an adrenal phaeochromocytoma with extension
      Into the right atrium: a case study.
AB  - A 30 year old female with an unexpected right adrenal phaechromacytoma invading
      the renal vein, the inferior vena cava and extending into the right atrium is
      presented. She also had BuddChiari syndrome due to invasion of the hepatic veins
      by the tumour. Additionally, the tumour had metastasised to the liver and the
      lungs. Despite elevated 24 hour urinary vanillylmandelic acid (VMA) the patient
      was normotensive pre-operatively. The patient underwent right adrenalectomy and
      extended nephrectomy with milking of the tumaur from the inferior vena cava.
      Unfortunately, the patient developed multiple hypotensive episodes and adult
      respiratory distress syndrome post-operatively and died three weeks after
      surgery.

PMID- 17451302
TI  - Polio Eradication by the year 2000.
AB  - In May l988, the Annual Meeting of the World Health Assembly (WHA) committed WHO
      to the exciting challenge of Global Eradication of Poliomyelitis by the year
      2000. The World accepted this challenge based on a number of scientific factors
      that had already been witnessed and certain other basic epidemiological factors
      concerning the transmission of the wild polio virus: 1. Smallpox had been
      eradicated and the global machinery and commitment for repeating such a feat
      could still be mobilised on She same lines to tackle another global menace; 2.
      The Pan American Health Organisation (PAHO) had already by May 1985 committed the
      American region to polio eradication by the year 1990. Although many people were
      initially sceptical of this initiative, it was quickly realised and recorded that
      the programme mounted by PAHO was achieving a high level of success and the goal
      of eradication was achievable; 3. Epidemiological! transmission factors that are
      persuasive to science for mounting eradication initiatives include: a) The wild
      polio virus moves from man to man only and has no wild animal reservoir to
      maintain it. b) An infected individual either dies, is crippled or fully recovers
      and remains immune without retaining or carrying the virus for many years (no
      carrier state) c) Available vaccine, particularly the oral (OPV) is not only
      capable of inducing long standing immunity in an individual but can, by
      multiplying in the gut, exclude or interrupt the circulation of the wild strain.
      The basic concepts and strategies for polio eradication recommended by WHO and
      now adapted globally are quite simple: 1. For each national expanded programme on
      immunisation (EPI) to raise the primary polio coverage rate with OPV to beyond
      80% as a routine in children under one year. Under such conditions of
      immunisation in every locality in every district and province, the incidence of
      paralytic polio is quickly reduced to very low levels. Most countries in the
      world have already achieved and exceeded this level of coverage. 2. For each
      country to conduct National Immunisation Days (NIDs) daring which 2 doses of OPV,
      one month apart, are administered to ALL children under 5 years of age
      irrespective of their previous vaccination status. This strategy boosts the
      immunity in (he children already vaccinated and catches those missed by routine
      services. The wild polio virus cannot live for long periods outside the human
      body, hence the NIDs effectively remove the wild polio virus from circulation.
      China was able to vaccinate over SO million children under 5ysars with OPV within
      two days. Currently the practice is for many neighbouring countries (even upto 15
      at a time) to simultaneously operationalise their NIDs on 2 to 3 days. 3. For
      each country to establish and operate an extremely sensitive surveillance system
      capable of detecting any new case of acute flaccid paralysis (AFP), Since
      paralysis can be produced by other conditions, it is necessary to back up the
      field surveillance with a reliable laboratory service capable of isolating
      poliovirus from the stool samples of paralytic cases. An isolated poliovirus
      would then have to be typed as wild or vaccine type strain. The strategies
      described above have all beers activated in all countries of the world and the
      world is already1 witnessing a dramatic disappearance of new cases of AFF. The
      International Certification Commission on Polio Eradication has established
      formal criteria by which countries can be certified polio-free. A polio-free
      status has to be maintained for at least 3 years in the countries of a region for
      that region to be certified as having eradicated the wild poliovirus. Global
      eradication will have been achieved if and when all regions in the world have
      been certified. The world is, no doubt, most grateful to all those international
      organisations, such as the Rotary International, WHO, UNICEF, national
      governments of the developed world through! donor agencies such as J1CA, US AID,
      D ANID A, etc., for the enormous resources that have been mobilised to
      operationalise EPI programmes for polio eradication. This gratitude is also a
      tribute in the late Dr. Albert Sabin, the discoverer of the oral poliomyelitis
      vaccine, which has been the major biological tool making it possible to eradicate
      the wild type poliovirus.

PMID- 17451303
TI  - A new methodological approach to the assessment of adolescent sexuality in Kenya.
AB  - The phenomenon of "adolescence" is one of the greatest public health concerns in
      Kenya. By age 19, about 85% of adolescents would have initiated coitus. Currently
      youth-sensitive population policies are yet to be developed. This is attributed
      to the complexity of the problem of adolescent sexuality. Research methodologies
      so far used in studying the problem have proved to be less reliable. In
      particular, adolescents tend to respond less truthfully when responding to
      questionnaires. It is therefore imperative to develop new, innovative and
      effective research approaches which can capture the underlying dynamics. This
      paper describes an approach which uses a methodology hereby named "Participatory
      Adolescents' Sexuality Assessment (PASA)" . Its implementation could provide
      effective research instruments leading to generation of new insights into the
      problem of adolescent sexuality. Details of the methodology are discussed.

PMID- 17451305
TI  - Perspective on noise induced hearing loss in Africa.
AB  - Noise-induced hearing loss (NIHL) occurs everyday in both occupational and non
      occupational settings in developed and developing countries. The good news is
      that NIHL is preventable through industrial control laws and programmes. In this
      paper, an attempt has been made to discuss the problem of NIHL, its relevance to
      African countries and strategies for its prevention.

PMID- 17451304
TI  - The role of airborne fungal spores from garbage dumps in respiratory diseases.
AB  - In recent years, there has been a growing global, regional and local concern
      about the potential health hazards associated with air pollution. Great attention
      has so far been paid to pollution associated with oxides of sulphur, CO, nitrogen
      oxides, O(3), trace organics, selected trace metals like lead, and miscelleneous
      suspended particulate matter. But, apart from these much talked about pollutants,
      urban air pollution associated with fungal spores from garbage pose a major
      environmental human health problem in most urban centres in Africa. Garbage
      probably accounts for most of the fungal spores in air, and, therefore, people,
      particularly those living close to heaps of garbage are exposed to very high
      concentrations of fungal spores. There is a possibility that a high correlation
      exists between the current incidence of respiratory infections and levels of
      fungal spores in the air. Air pollution by fungal spores has not been a matter of
      great concern in the past, and therefore, it is time we drew the
      environmentalists' attention and public awareness on this real and potentially
      hazardous issue. In this article, potential human health hazards resulting from
      moulds growing on crude garbage dumps in the vicinity of human habitation are
      discussed.

PMID- 17451306
TI  - Outbreak of dysentery Is Kenya due to multi-resistant polyclonal strain of
      Shigella dysenteriae type 1.
AB  - Sixty-eight strains of multi-drug resistant Shigella dysenteriae type 1 were
      isolated from outbreaks of severe dysentery in three areas of Kenya, namely,
      Kisumu, Mombassa and Nairobi. The strains were tested for their susceptibility to
      seven antibiotics. Plasmids were extracted to study their variety and conjugated
      with Escherichia coli K12 to identify the plasmid coding for the resistance gese.
      All the strains were resistant to ampicillin, trimethoprim-sulfamethoxazole (S
      T), tetracyciine and chloramphenicol. They were sensitive to gentamicin,
      kanamycin and nalidixic acid. Part of the resistance was found to be plasmid
      mediated and the sizes of plasmids coding resistance gene wereSMDaand 19MDa.
      These piasmids coded resistance for ampicillin, trimethoprim-sulfamethoxazole,
      tetracyciine and chloramphenicol. Verotoxin (VT) production was demonstrated in
      80% of the strains by oligonucleotide DNA-DNA gybridization of whole cells with
      the VT-probe. In view of the extent of drug resistance exhibited by Shigella
      dysenteriae Type 1 in this study, we recommend the use of nalidixic acid as a
      first choice of treatment in multiresistant S. dysenteriae Type 1 dysentery
      outbreaks. Compared to the other two agents that the pathogen was sensitive to,
      nalidixic acid is relatively cheap with the cost of 7 days treatment for an adult
      being approximately five US dollars. Resistance to nalidixic acid has to be,
      however, closely monitored as S. dysenteriae Type 1 has been reported to develop
      resistance to this drug over time.

PMID- 17451307
TI  - Urinary tract infection in patients with short-term indwelling.
AB  - Seventy patients (44(62.9%) females) requiring short-term urinary bladder
      catheterisation at the Kenyatta National Hospital, Nairobi formed the study
      population. Their mean ages +/- SD was 41+/- 26 years (range 13-100 years). The
      common indications and objectives for catheterisation included keeping the
      environment dry (41.1%), relieving urinary retention (27.0%) and urinary
      incontinence (24.3%). Urinary Tract Infection (UTI) was documented in 48 (68.6%)
      of the patients. The commonest infection organisms were Klebsiella pneumoniae,
      Escherichia coli and Proteus mirabilis, the three accounting for 78.6% of the
      infections. Female gender and increasing age increased the risk of catheter
      associated UTI. The risk of having catheter-associated UTI was higher in patients
      with medical and surgical conditions than in those with obstetric and gynaecology
      conditions. Patients who were on systemic antibiotics for other conditions
      acquired UTI less often (27%) than those who were not undergoing antibiotic
      therapy. The organisms isolated showed marked resistance to commonly available
      antibiotics. We conclude that UTI, due to resistant organisms, is common in
      patients undergoing acute urinary bladder catheterisation in our setting and
      recommend that urinary bladder catheterisation should be avoided whenever
      possible. In a situation where this is inevitable, closed drainage systems should
      be used for the shortest duration possible.

PMID- 17451308
TI  - Evaluation of antenatal risk factors lit Cape Verde.
AB  - The prevalence of antenatal risk factors and their association with adverse
      pregnancy outcome were prospectively studied in the county of Praia, Cape Verde.
      Of 4693 women registering for antenatal care, 8% were randomly selected from
      October 1991 through December 1992. Eventually 358 women were observed until
      puerperium when a physical examination and a structured interview took place.
      Three out of four women of the cohort were exposed to risk factors according to
      the existing risk classification in Praia, and 9% presented high risk factors.
      Thirty two percent of the cohort faced adverse pregnancy outcomes. Adverse
      pregnancy outcomes were significantly increased among women who presented high
      risk factors, but 82% of all adverse outcomes occurred among other women. The
      antenatal risk classification investigated cannot be considered an effective tool
      for detection of women at risk of adverse pregnancy outcome.

PMID- 17451309
TI  - A sero-epidemiology cross-sectional nationwide study of the prevalence of human
      immunodeficiency virus in Zimbabwe 1989-1991.
AB  - Between 1989 and 1991 a nationwide cross-sectional study of 2837 voluntary
      subjects was performed in all nine provinces of Zimbabwe to estimate the
      prevalence of HIV by age, sex and residence (urban/rural). The study areas were
      15 randomly selected districts from each of the nine provinces. All collection of
      blood samples was done at schools, clinics, factories and rural health centres
      and samples were tested for anti HIV 1 and 2 using both the Abbott Recombinant
      HIV l/2,3rd generation and the Wellcozyme HIV 1+2. The overall prevalence was
      6.9% (95% confidence interval (CI): 6.8-7.0). It was significantly higher in
      females (8.2%) than in males (5.1%) (P = 0.002) and in urban (11.9%) as compared
      with rural areas (3.0%) (P=0.0005). Analysing the study as a case-referent study
      resulted in an odds ratio (OR) of 1.7 for females as compared with males and 4.3
      for urban as compared with rural areas. The difference between urban and rural
      areas remained after standardisation for age, sex and year of data collection but
      on a lower level (OR=2). The prevalence was higher in provinces where a higher
      proportion of the subjects was classified as resident in urban areas with one
      exception (Masvingo province in the southern part of the country (20.8%) and
      highest an the capital Harare (12.5%). The differences between the provinces
      remained after standardisation for age, sex and year of data collection. The
      prevalence of HIV in Zimbabwe was high already in 1989 and increased rapidly
      between 1989 and 1991, especially in urban areas.

PMID- 17451310
TI  - Effect of route of administration on systematic availability of oxamniquine in
      the rabbit.
AB  - Eight New Zealand white rabbits (4 females, 4 males) each received oxamniquine
      (15 mg kg(-1)) orally, rectally, intravenously and via the hepatic portal vein in
      a random cross-over study. Serial plasma samples were obtained for up to 10 hours
      post drug administration and the bioavailable fraction was calculated, with
      reference to the intravenous route, from areas under plasma drug concentration
      time profiles. Estimated fractions available were approximately 1.0, 0.45 and
      0.46 respectively, for portal vein, oral and rectal routes. Hepatic "first-pass"
      metabolism appeared to be negligible. Low oral availability suggested incomplete
      absorption and/or metabolism within gastrointestinal wall. Rectal administration
      resulted in comparable availability to oral administration. These results suggest
      that if a suitable formulation can be developed, then rectal administration of
      oxamniquine may provide an alternative to oral administration in patients who
      cannot take drug orally.

PMID- 17451311
TI  - Oxamniquine inhibits metabolism of caffeine, hexobarbitone and antipyrine in vivo
      in mice.
AB  - Inhibition of hepatic metabolism of caffeine (as assessed from expiration of
      (14)CO(2) resulting from N-demethylation of (14)C-labelled caffeine),
      hexobarbitone (as assessed from sleeping times) and antipyrine (as assessed from
      expiration of I4CO2 resulting from the oxidation of "C-labelled antipyrine) was
      studied in male GB-1 mice administered a single SO mg kg-1 oral dose of the
      schistosomicidal drug oxamniquine. Metabolism of caffeine, catalysed by
      cytochrome P-4S0 1A2(CYP1A2), was inhibited most, while hexobarbitone and
      antipyrine metabolism were inhibited to a lesser, though significant, degree.
      These results indicate a need for further studies to investigate possible
      clinically relevant inhibition of hepatic drug metabolism by oxamniquine.

PMID- 17451312
TI  - Civil turmoil in Africa: a potential setback in the fight against diseases.
AB  - Africa continues to face enormous challenges in her efforts to provide health
      care and to control diseases, particularly in the face of dwindling financial
      resources, inadequate facilities and supplies, and increased demand for health
      services. The situation is further compounded by new challenges created by the
      emergence of new infections, re-emergence of diseases hitherto thought to have
      been put under control, changes in epidemiological patterns and manifestations of
      existing diseases. All these factors have an overall effect of increasing disease
      incidences, morbidity and mortality, thus, hindering efforts to control disease
      in the continent.A new pattern is also emerging which is likely to be a major
      setback in the control and fight against infectious diseases in Africa. In recent
      years, several parts of Africa have experienced civil disruptions that have
      resulted in the displacement of large numbers of people. The displaced end up in
      the refugee camps either within their own countries or across the borders, in
      neighboring countries. Such disruptions are likely to become a setback in the
      fight against diseases in a number of ways. 1. Besides deaths and injuries
      resulting from the physical confrontations in such situations, the displaced
      people, who end up in camps, live under conditions characterized by overcrowding,
      poor sanitation, inadequate food and water. Such conditions favour disease
      outbreaks, and the people live under constant threat of contracting diseases.
      Particularly at risk are vulnerable groups such as children, pregnant mothers,
      and elderly. Inspite of efforts made, usually through internationally funded
      agencies, to provide food and health care, diseases outbreaks are common in camps
      for the displaced people. 2. In many instances, the displaced end up in a
      neighboring country, far away from the actual focus of trouble. Diseases outbreak
      affecting people living in camps will most likely spread to the general
      population of the host country. Infectious diseases spread rapidly from the
      initial focus of outbreak, often with devastating results. Usually, the already
      overburdened health care authorities of the host country will be expected to
      respond to such a crisis. However, because of the meager resources available for
      health care and diseases control in many countries, it is always difficult to
      adequately deal with unexpected disease outbreaks. The situation may become even
      more complicated if the infectious agents display unusual patterns such as high
      virulence or failure to respond to commonly used drugs. In other words, it is
      possible that known infections with unusual characteristics or manifestations may
      be introduced into an area, and spread rapidly to other parts of the country, and
      probably beyond. Morbidity and mortality associated with such outbreaks is likely
      to be high and devastating. 3. There are always fear that migration of people
      from one region to another may lead to the introduction of diseases into
      geographical areas they did not exist before. Migration of large number of people
      into a new area may accelerate spread of diseases. As civil turmoil often affects
      large numbers of people, such an event is likely to have a greater impact in
      terms of disease spread. 4. The displaced people will have lived in a neighboring
      country for several months or even years, during which time they will have
      acquired new infections, most probably, with different characteristics from those
      in the home country. Thus, they may also introduce new diseases or new strains of
      disease-causing organisms, acquired from the host country into their home
      countries on return, once the situation returns to normal. Control of new
      diseases or strains of infections agent could pose challenges to the health
      authorities of their home countries. In other words, civil disruptions cold lead
      to diseases outbreaks and rapid spread of known or new diseases, factors that
      will increase disease incidences, morbidity and mortality on the continent. This
      is a major setback in the fight against diseases in Africa, particularly in the
      face of dwindling resources required for health care and diseases control. One
      way in which potential spread of diseases could be controlled in situations of
      turmoil is through rapid response in the provision of food, shelter, medicine and
      sanitary facilities to the displaced. Adequate knowledge of possible diseases
      that are likely to be encountered in such communities is essential and health
      care personnel must be prepared to face these challenges. Research into health
      issues of the displaced persons in essential in providing solutions associated
      with turmoil. Health research institutions have a key role to play in this
      regard. The expertise and facilities available in such institutions could be
      used, for instance, to accurately identify infectious agents, to detect unusual
      manifestations of diseases or the infectious agents, both within the refugee
      camps and beyond. Such initiatives will complement the efforts of health care
      agencies and the country health care institutions. In this issue, Magambo et al
      (pp149-156) have attempted to look at health problems of people living in
      southern Sudan, an area that has, for along time, experienced civil turmoil.
      Understanding of health problems of southern Sudan will not only provide a basis
      for instituting diseases control measures in this region, but will also provide a
      basis for instituting preventing measures within the affected country, and in the
      neighboring regions.

PMID- 17451313
TI  - Health services and the adolescent health situation in a rural setting: the
      Kenyan experience.
AB  - This study examined the adolescent health situation in Siaya District. The
      findings indicate that there are no particular health services specifically
      targeting the adolescent in the district. The adolescent health situation in the
      district is badly off and prevalence of diseases is high amongst them. They are
      faced with STDs/AIDS, pregnancies, drug abuse, abortion, alcoholism among others.
      The adolescent in the district are not aware of the existing health services that
      could be of help to them. They are not aware of their general and reproductive
      health as it were, but they are very much aware of contraceptives. The study
      revealed that their attitude towards the existing medical and nursing services
      including the medical staff is very negative. They do no have proper information
      system and the health facilities are inaccessible to them. Teachers and radio
      play a major part in disseminating information to them. The health staff are very
      much aware of the adolescent health needs. Most health staff have communication
      problems with the adolescents. Not so many schools offer heath services and for
      those which offer, it is only simple diagnosis and treatment. Students dropping
      out of schools are mostly victims of pregnancies and drug-abuse or alcoholism.
      This revealed that the adolescents in the district need immediate help as far as
      their health needs are concerned.

PMID- 17451314
TI  - A community-based study on utilisation of maternity services in rural Zimbabwe.
AB  - To estimate the degree and pattern of utilization of institutional maternity
      services in a rural area of Zimbabwe, a cross-sectional study was performed in
      Gutu district about 250 kilometers south of the capital Harare. In August, 1991,
      12 out of 43 wards in the district were randomly selected and in each ward about
      40 women (in total 520) who had delivered in the previous 12 months were randomly
      selected and interviewed. There was a high degree of utilization of institutional
      maternity services by the women (96% 79% and 74%) for antepartum, intrapartum and
      postpartum care respectively). Women sought this care from a multiplicity of
      sources depending on a variety of social, geographical and service factors. Very
      few women (17%) had total pregnancy care at the rural health centre. There was a
      significant association between the actual place of delivery and nulliparity,
      whether the previous delivery took place at home, whether the family belonged to
      the Apostolic Faith sect, and whether the husband spent most time in urban area.
      For nulliparity, previous delivery at home and belonging to the Apostolic Faith
      sect the proportion of women delivering at home, at the rural health center/urban
      maternity clinic, and at hospital was statistically significant. The few
      maternity waiting shelters that were available lacked basic amenities and were
      unattractive to the mothers even though 65% either used them or could have done
      so if they were available.

PMID- 17451315
TI  - Anaemia in pregnancy: a major health problem with implications for maternal
      health care.
AB  - Women (n=2235) registering for antenatal care in two maternal and child health
      clinics in the Dar es Salaam area between June, 1991 and June 1992 had their
      haemoglobin (Hb) measured by use of a HaemoCuer haemoglobinometer. The prevalence
      of anaemia Hb<10.5 g/dl) was 60% while severe anaemia (Hb<7.0 //dl) was present
      in 4%. Young nullparous women, those who register for antenatal care late in the
      third trimester, and undernourished women constitute high risk groups also for
      severe anemia and require special attention. No single maternal characteristics
      or combination thereof was useful to identify a group of screening. The current
      national Hb level for referral to hospital (8.5 g/dl) identified 20% of the
      pregnant population. Most of these can successfully be treated and followed at
      the primary care level. To comply with the available means for care in the Dar es
      Salaam area, it is proposed that the cutoff level for referral be changed to
      <7g/dl. Appropriate methods to screen for anemia at primary health care (PHC)
      level must be explored and instituted. Training of antenatal care (ANC) providers
      in clinical identification of anemia and supply of haematinics must be improved
      and early booking for ANC promoted. Public health measures to improve the general
      nutrition and iron intake of all women are necessary to reduce this serious
      health problem in pregnancy.

PMID- 17451316
TI  - Factors that determine utilization of modern contraceptives in East, Central and
      southern Africa.
AB  - A cross-sectional study to determine modern contraceptives utilization among
      women aged between 15 and 19 years was performed between September and October,
      1991 in 5 countries of East Central and Southern Africa. The study involved both
      rural and urban area of Kenya, Uganda, Mauritius, Swaziland and Zambia. A total
      of 4513 women were interviewed of whom 2418 (53.6%) were from the urban areas
      while 2096 (46.4% were from the rural areas. The percentage distribution of
      contraceptive users was 33.2% in urban and 48.9% in rural areas. The proportion
      of users of traditional/natural contraception was 38.5%. Overall the prevalence
      of contraceptive use was 29.5%. Thus the natural/traditional methods were most
      popular in the region. The user rate of modern contraceptive methods ranged from
      6.8% for Zambia to 60% for Mauritius. The study revealed that contraceptive
      prevalence rates were higher among women in urban areas (60%) than in rural areas
      (40%). The main factors influencing contraceptive use in order of importance
      included distance from residence to clinics, level of education attained, parity,
      marital status, approval by husbands/boyfriends and knowledge of family planning
      methods. Contraceptive use was highest in the age group of 20 to 34 years while
      it was lowest among young women aged 15-19 years.

PMID- 17451317
TI  - Importance of anti-Plesiomonas antibody in the protection of rats against
      infection by Plesiomonas Shigelloides.
AB  - Rabbit anti-antibody raised against Plesiomonas shigelloides infections using
      standard immunological procedures. Ten (50%) of 20 rats died when only P.
      shigelloidess was injected while 2(10%) died [P < 0.05]; following injection of
      another group of 20 rats with P. shigelloides 24hours after administration of
      rabbit-Plesiomonas anti-antibody. In another scheme, 14(70%) of 20 rats died when
      p.shigelloides and colloidal carbon particles (CCP) were administered while only
      4(20%) died (p<0.05) following injection of P. shigelloides and CCP 24 hours
      after administration of rabbit-Plesiomonas anti-antibody. No death was recorded
      for control rats which received only CCP. This study highlights a novel approach
      in the management or prevention of P. shigelloides infection in our environment.

PMID- 17451318
TI  - Hemorrhagic fevers: few clues after 25 years.
AB  - There is a high prevalence of Ebola antibodies found in the Kenya population,
      related to geographical area and season, although the clinical disease was never
      found and the virus was not isolated. A field study was carried out in 7
      hospitals in western Kenya, 1986 -1987 (including surveillance studies in suspect
      areas), to intensify collection and transport of samples, testing facilities,
      patient observation with record keeping and follow-up. This study involved 1109
      admitted patients with fever and/or bleeding, 155 contacts of haemorrahagic fever
      antibody (Hfab) patients, and 916 people in suspect areas. Respectively 160,44
      and 80 persons were found Hfab positive mainly to Ebola, using an indirect
      immunofluorescent assay. From 676 viral cultures no virus was isolated. A
      relationship between antibody titres and ecological factors, social habitat, age,
      sex or season was not found. The non-specificity of IF testing was demonstrated
      by: 1) the disagreement between the results of two reference laboratories; 2) the
      unpredictability of the titre conversation course; and 3) by proving a
      significant cross-reactivity with Borrelia burgdorferii antibodies, Plasmodium
      falcparum antibodies and Salmonella typhi antibodies. Renewed testing in 1995 of
      90 positive sera (with low titres) showed 19 sera to be positive by Elisa (2 in
      Zaire, 1 in Sudan, 9 in Reston and 7 in Cote d'Ivoire) from which 4 were
      confirmed by IFI 2 in Reston and 2 in Cote d'Ivoire. These findings are more
      proof that non-human virulent strains of Filoviridae, especially Ebola virus, are
      around in Kenya.

PMID- 17451319
TI  - Prevalence of Oncocerca volvulus in Southern Sudan.
AB  - Onchocerciasis is endemic in southern Sudan. The prevalence in human population
      may range from 10% to 40%. In the Eastern Equatorial Region of Southern Sudan,
      more cases are found in Nimule on the Sudan-Uganda border than in rural highlands
      of Labone and Chukudum basins. Onchocerciasis was highest in males (with a
      prevalence of 70.2% based on data from hospital records)) than in females, with
      prevalence of 19%. Overall, prevalence of onchocerciasis in children was
      10.8%.Considering cost-effectiveness, public health priorities and the security
      situation in this area, we recommend active search on onchocerciasis cases in the
      community and treatment.

PMID- 17451320
TI  - Prevalence of malaria in southern Sudan.
AB  - The prevalence of malaria in the human population of southern Sudan was studied
      during March to April, 1996. A total of 330 people including adults and children
      were screened for malaria by microscopic examination of Giemsa stained thick and
      thin blood smears prepared from a finger prick sample. Plasmodium falciparum was
      the only malaria parasite detected in blood smears in the present study, even
      though hospital records indicated presence of P. vivax. About 24.5% of those
      examined were infected. .

PMID- 17451321
TI  - Prevalence of human hydatid disease in southern Sudan.
AB  - A total of 3443 people were screened by ultrasound to determine the prevalence of
      hydatid disease in southern Sudan. Hydatid cysts were found in 16 (0.5%) of the
      people screened. Thirteen of the 16 hydatid cases were from among the Bouya
      people who showed an overall hydatid prevalence of 2% by ultrasound. All ultra
      sound positive cases were further confirmed by dot-blot ELISA. At the time of the
      survey, Chukudum Hospital had five cases with histories and clinical
      manifestations consistent with hydatidosis. However, on scan examination only
      three of them were confirmed to be cases of hydatid disease. The proportion of
      hydatid infected women in south-western Sudan was almost twice that of men (M:F
      ratio of 1:1.7), with most of those infected being women in the child-bearing age
      bracket. Dogs are common in this area and they could be the main reservoirs of
      Echinococcus granulosus in the Sudan. Due to the low prevalence of hydatid in
      humans in the study area, and the dispersed nature of the population, it is
      recommended that hydatid control measures for south-western Sudan include an
      educational component coupled with treatment of the infected people.

PMID- 17451322
TI  - Pneumovesicum method in en-Bloc laparoscopic nephroureterectomy with bladder cuff
      resection for upper-tract urothelial cancer.
AB  - BACKGROUND AND PURPOSE: A novel technique for managing the distal ureter and
      bladder cuff during laparoscopic nephroureterectomy is introduced. TECHNIQUE: The
      procedure consists of three steps: (1) cystoscopy and PediPort (Tyco) insertion;
      (2) establishment of pneumovesicum and intramural ureter mobilization; and (3)
      laparoscopic nephroureterectomy. The use of PediPorts, a 5-mm lens, and Ski
      needles greatly facilitates the pneumovesicum. The ureteral orifice is closed,
      and the intramural ureter is dissected out with the patient in the lithotomy
      position. Laparoscopic nephroureterectomy is then accomplished with the patient
      in the lateral position. RESULTS: The postoperative course was uneventful, and
      the pathology examination showed clear margins. CONCLUSION: Pneumovesicum is a
      minimally invasive approach that provides an excellent endoscopic view. It is an
      oncologically sound method, as the ureteral orifice is closed early, and the
      chance of cancer-cell spillage is minimized by the use of gas instead of liquid
      in the bladder. Moreover, the procedure is not technically demanding.

PMID- 17451323
TI  - Endoscopic lymphadenectomy for penile carcinoma.
AB  - BACKGROUND AND PURPOSE: Groin dissection remains the gold standard for the
      treatment of penile carcinoma that has metastasized to the inguinal lymph nodes.
      However, it is associated with wound-related complications. Modified groin
      dissection offers a less-radical approach without compromising oncologic
      outcomes. We present our technique for endoscopic lymphadenectomy for penile
      carcinoma (ELPC). PATIENTS AND METHODS: Eight patients with clinical stage T(2)
      N(0-3)M(0) penile carcinoma underwent ELPC. Preoperative Doppler ultrasound
      mapping of the inguinal lymph nodes and the saphenous vein was performed.
      RESULTS: Fourteen lymphadenectomies, including superficial with or without deep
      inguinal and pelvic-node dissection, were completed in eight patients. The median
      operative time was 91 minutes (range 50-150 minutes), and the mean number of
      nodes removed was 9 (range 4-15). No perioperative complications occurred.
      Lymphoceles developed in three groins (23%). No wound-related complications were
      seen. CONCLUSIONS: The ELPC is a safe and feasible technique that appears to
      diminish the wound-related complications associated with the standard open
      approach.

PMID- 17451324
TI  - Robot-assisted laparoscopic distal ureterectomy and ureteral reimplantation with
      psoas hitch.
AB  - For midureteral and distal-ureteral tumors not amenable to endoscopic resection,
      distal ureterectomy with ureteral reimplantation is a treatment option. When
      ureteral length is insufficient for direct reimplantation, additional length can
      be gained with either a psoas hitch or a Boari flap. We describe our technique
      for robot-assisted laparoscopic distal ureterectomy and ureteral reimplantation
      with psoas hitch.

PMID- 17451325
TI  - Setting a new standard for topical therapy of upper-tract transitional-cell
      carcinoma: BCG and interferon-alpha2B.
AB  - BACKGROUND AND PURPOSE: We report our office-based technique and results of BCG
      and interferon-alpha2B (BCG-IFN) for upper-tract transitional-cell carcinoma
      (TCC). TECHNIQUE: Papillary lesions were ablated endoscopically after biopsy.
      Office flexible cystoscopy was performed, and a 0.038-inch guidewire or Glidewire
      was advanced into the renal pelvis. A 5F ureteral catheter was placed over the
      wire, and a free flow of urine was confirmed. Half-strength BCG + 50 million
      units of IFN was infused under low pressure for 1 hour. The ureteral catheter was
      removed, and patients were instructed to void 1 hour later. RESULTS: Between 2000
      and 2006, 10 patients with a median age of 72 years were treated with BCG-IFN for
      upper-tract TCC in 11 renal units. Follow-up ureteroscopy with or without biopsy
      was performed after a 6-week induction to evaluate response. Complete responders
      were placed on a maintenance regimen. With a median follow-up of 24 months, 8
      patients (80%) demonstrated a complete response (CR) to therapy, and 2 had a
      partial response (decrease in tumor size, number, or both). Six patients with a
      CR have continued on maintenance therapy. There were no side effects or
      complications with the instillation therapy. CONCLUSION: We describe a safe,
      minimally invasive, and effective office-based technique for upper-tract BCG-IFN
      instillation.

PMID- 17451326
TI  - Optimizing outcomes in laparoscopic urologic training: toward a standardized
      global consensus.
AB  - BACKGROUND AND PURPOSE: Laparoscopic urologic surgery (LUS) is one of the fastest
      growing subspecialties in the surgical world. The procedures require technical
      expertise and finesse; unlike their open counterparts, there is significant
      limitation in the margin for error. Various ethical, medicolegal, and health
      economy demands have made training in laparoscopic urologic surgery challenging.
      Whereas several groups have sought solutions through models, there remains a lack
      of consensus on the optimal training program. We review the current LUS programs
      with a conscious effort to decipher the basic tenets of an optimal training
      program and propose training models based on published evidence, in conjunction
      with current trends in LUS. METHODS: A literature search of MEDLINE, Pubmed,
      CINAHL, EMBASE, the Cochrane Database of Systematic Reviews, and Google Scholar
      was performed, seeking publications from January 1970 to July 2006 on
      laparoscopic surgical training pertaining to urology. Additionally, we looked at
      pertinent abstracts of the annual meetings of the American Urological
      Association, the European Association of Urology, and the World Congress of
      Endourology for the period January 1996 to and inclusive of August 2006. RESULTS
      AND CONCLUSIONS: To date, no study has documented a global consensus on optimal
      LUS training programs. Our search identified several models, some of which were
      applied successfully in the form of minifellowships. There remain no clear
      guidelines on the optimum LUS training program. The optimal program may need to
      be tailored to individual units, based on resources (this includes country
      specific health economics, mentor availability, and caseload). Further studies
      are needed to help elucidate how individual programs can be initiated with a
      global minimum standard applicable to all training programs.

PMID- 17451327
TI  - Observations on intrarenal geometry of the lower-caliceal system in relation to
      clearance of stone fragments after extracorporeal shockwave lithotripsy.
AB  - PURPOSE: To study the intrarenal geometry of the lower-caliceal system in
      patients with and without residual fragments after extracorporeal shockwave
      lithotripsy (SWL) and to formulate a summarizing mathematical expression of
      relevant variables. PATIENTS AND METHOD: In a series of patients consecutively
      treated by SWL, we analyzed the geometric anatomy in 47 patients with (group R)
      and 47 without (group NR) residual fragments in long-term follow-up. A number of
      distances and angles previously described in the literature were measured, to
      which was added the distance between the stone-bearing calix and the vertex of
      the lower renal lip (CL) and the angle (delta) this line formed with a vertical
      line. RESULTS: There were significant differences between the groups in terms of
      infundibular length (P = 0.009), CL (P = 0.0020), and lower-caliceal height, CH
      (P = 0.0004). The calix width and the various angles did not differ significantly
      between the groups. The quotient CH/CL was used to calculate cos delta, and a
      summarizing expression (Index LC) was given the form CH(2)/CL which equals CH x
      cos delta. This index was significantly different in groups R and NR (P =
      0.0036). Approximately 4% of the patients in group NR, compared with 28 percent
      in group R, had Index LC values >25. CONCLUSION: Index LC, as an expression of
      the geometry of the lower-caliceal system, might be useful for simple description
      of the lower-caliceal anatomy and supportive for decisions on the use of fragment
      clearance-facilitating procedures or the selection of a more invasive approach
      than SWL.

PMID- 17451328
TI  - Introducing a new sealant applicator for easy, safe, and quick closure of a mini
      percutaneous nephrolitholapaxy access tract.
AB  - PURPOSE: To achieve better hemostasis after mini-percutaneous nephrolitholapaxy
      (mini-PCNL), we developed a new application device that can be used to close the
      renal-access tract with gelatin matrix hemostatic sealant (GMHS). PATIENTS AND
      METHODS: After mini-PCNL was performed on 11 patients, a Double-J ureteral stent
      was placed antegrade. After retraction of the 18F Amplatz sheath out of the
      collecting system under vision without irrigation, the urothelium collapsed. The
      15F metal applicator with a 10F working channel was then inserted and GMHS
      injected during further retraction of both the device and the Amplatz sheath. The
      skin was closed with Steri-strips. RESULTS: The renal parenchymal tract of the
      mini-PCNL can be sealed in 15 to 50 seconds. Postoperatively, no urinoma was
      observed. All patients had an uneventful follow-up. CONCLUSION: Closing the track
      of the mini-PCNL with the new application device and GMHS is a safe, easy, and
      quick alternative to the common nephrostomy tube.

PMID- 17451329
TI  - Ureteroscopic management of ureteral calculi in children.
AB  - PURPOSE: To evaluate the efficacy and safety of rigid ureteroscopy for the
      treatment ureteral calculi in children. PATIENTS AND METHODS: Between January
      2002 and January 2006, 16 boys and 25 girls with an average age of 9.5 years
      (range 3-15 years) were treated with a 95F rigid ureteroscope for stones 4 to 10
      mm (mean 5.6 mm) in 46 renoureteral units (RUUs), and the results were evaluated.
      The stones were located in the upper ureter in 4 RUUs, the middle ureter in 15,
      and the lower ureter in 27. Dilatation of a tight ureteral orifice was necessary
      in 17 cases (36.9%). RESULTS: On examination during ureteroscopy, all calculi
      were well fragmented, and in 33 patients (94%), stone fragments were removed
      directly. Stones were fragmented with pneumatic lithotripsy in 23 RUUs and
      removed by forceps with or without fragmentation in the remaining 23. Whereas the
      treatment was successful in 36 children (87.8%), it was unsuccessful in 5 (12.2%)
      secondary to bleeding and mucosal injury in 3 children (7%; 1 middle- and 2 upper
      ureteral stones) and severe ureteral stenosis with kinking in 2 (4.8%; 1 middle-
      and 1 upper-ureteral stone) children. In two other cases, although the fragments
      in the upper portion of the ureter could be reached with the ureteroscope, the
      stones migrated into the renal collecting system during pneumatic lithotripsy and
      were treated successfully with subsequent SWL (4.8%). At the end of the
      procedure, a 4.8F Double-J stent was left in place in 9 cases. There were no
      serious complications, and the children were not specifically evaluated for
      postoperative vesicoureteral reflux. Follow-up ranged from 1 to 36 months with an
      average duration of 22.4 months. CONCLUSION: With the aid of the experience
      gained in the adult population and careful instrumentation, we believe that, in
      skilled hands, rigid ureteroscopy can be applied in a safe and efficient manner
      for stones located in different portions of the pediatric ureter.

PMID- 17451330
TI  - Does previous open nephrolithotomy affect the outcome of percutaneous
      nephrolithotomy?
AB  - PURPOSE: To determine the effects of previous open nephrolithotomy on the results
      and morbidity of subsequent percutaneous nephrolithotomy (PCNL). PATIENTS AND
      METHODS: Between March 2005 and January 2006, 89 patients underwent PCNL at our
      institution. We compared the patients who had had previous open surgery on the
      same kidney (group 1; n = 27) with those who had had no previous surgery (group
      2; n = 62). The two groups did not differ significantly in age (45.4 v 44 years),
      stone burden (361.3 mm(2) v 482.4 mm(2) ), stone number, or laterality. Operative
      time, hospital stay, success rate, visual analog pain scores 8 hours after
      surgery, analgesic doses (diclofenac sodium), and intraoperative and
      postoperative complications were compared. RESULTS: There were no differences in
      operating time, postoperative analgesic doses, pain scores, intraoperative and
      postoperative complications, the number of accesses, or the stone-free rate.
      CONCLUSIONS: The morbidity and efficacy of PCNL are similar in patients who have
      had previous open nephrolithotomy and those having no previous surgery. Previous
      open surgery does not affect the success of PCNL.

PMID- 17451331
TI  - Port-site metastasis after laparoscopic partial nephrectomy: Case report and
      literature review.
AB  - Local recurrence and port-site metastasis remain a concern in urologic
      laparoscopic oncologic surgery. Portsite recurrence of renal-cell carcinoma after
      retroperitoneal and transperitoneal radical nephrectomy has been well documented.
      We report the first case of a port-site metastasis secondary to a partial
      nephrectomy and perform a literature review of this subject.

PMID- 17451332
TI  - Pure laparoscopic radical nephrectomy for stage T(3b) renal-cell carcinoma: more
      than 2-year follow-up.
AB  - BACKGROUND AND PURPOSE: Renal-vein tumor thrombus associated with renal
      malignancy has traditionally been approached with open surgery, and preoperative
      diagnosis of stage T(3b) renal tumors often mandates open surgery. However, early
      arterial division and "milking" of the thrombus away from the inferior vena cava
      may facilitate laparoscopic surgery. We describe our single-surgeon experience
      with laparoscopic nephrectomy in patients with tumor extension into the renal
      vein. PATIENTS AND METHODS: Among 240 laparoscopic nephrectomies performed by a
      single surgeon from 2002 to 2005, six patients (2.6%) were found to have renal
      vein tumor thrombus. These patients included three men and three women with a
      mean age of 55.8 years (range 43-78 years). Data collected prospectively were
      evaluated to characterize this cohort. RESULTS: All six tumors were right-sided,
      stage T(3b), and all were managed laparoscopically without major complications.
      Three tumors were suspected to have renal-vein thrombus on preoperative imaging;
      the other three tumor thrombi were discovered on pathologic examination. The mean
      tumor size was 9.5 cm (range 7.5-11.5 cm). Two tumors were grade 2, three were
      grade 3, and one patient had a grade 4 rhabdoid cell-type tumor. At a mean follow
      up of 27 months, all patients were without evidence of disease with the exception
      of the patient with grade 4 disease, who developed recurrence in the chest.
      CONCLUSION: Laparoscopic nephrectomy for tumor with renal-vein thrombus can be
      accomplished safely with adherence to proper oncologic techniques.

PMID- 17451333
TI  - Combined robot-assisted laparoscopic nephroureterectomy and radical
      prostatectomy.
AB  - A 57-year-old man with prostate cancer and transitional-cell carcinoma of the
      kidney underwent a combined robot-assisted prostatectomy and hand-assisted
      laparoscopic nephroureterectomy with robot assistance. We describe the initial
      report of this combined operation and the novel use of the da Vinci robot for
      extravesical bladder-cuff excision and repair.

PMID- 17451334
TI  - Transmesocolic pyeloplasty: experience of a single center.
AB  - PURPOSE: We present our experience with dismembered left-sided pyeloplasty using
      a transmesocolic technique as a way to reduce operative time and facilitate
      repair by avoiding colon displacement. PATIENTS AND METHODS: Between January 2004
      and January 2006, a total of 11 transmesocolic laparoscopic pyeloplasties were
      performed by the same surgeon at our institution. The mean patient age was 41.6
      years (range 14-65 years). Operative records and follow-up were reviewed.
      RESULTS: A dismembered Anderson-Hynes pyeloplasty was carried out in nine
      patients (82%), while a Y-V plasty (9%) and a Fengerplasty (9%) were done in one
      patient each. Crossing vessels were observed in 8 patients (73%). A ureteral
      stent was left in all patients. The mean operative time was 88.6 minutes (range
      60-125 minutes), and blood loss was minimal. Compared with classic
      transperitoneal laparoscopic left pyeloplasties, transmesocolic cases showed a
      significant reduction in operative time (88.6 minutes v 117 minutes; P < 0.05).
      There were no intraoperative complications or open conversions. The mean hospital
      stay was 2.1 days (range 2-3 days). Only 1 patient (9%) demonstrated narrowing of
      the anastomosis, which occurred 12 months after a Fengerplasty. CONCLUSIONS: The
      transmesocolic approach to a dilated left pelvis enables a shorter operative time
      without increasing morbidity. More patients and longer follow-up are necessary to
      determine its effect on convalescence.

PMID- 17451335
TI  - Retroperitoneoscopic partial adrenalectomy for large adrenocortical oncocytoma.
AB  - A young woman had mild hypertension, and on evaluation, a large tumor arising
      from the right adrenal gland was found. The tumor was hormonally inactive.
      Retroperitoneoscopic partial adrenalectomy was carried out. The histopathology
      report described adrenocortical oncocytoma.

PMID- 17451336
TI  - Biological glues and collagen fleece for hemostasis during laparoscopic partial
      nephrectomy: technique and results of prospective study.
AB  - PURPOSE: The aim of this prospective study was to evaluate the advantages or
      disadvantages of the use of fibrin glue and collagen fleece during laparoscopic
      partial nephrectomy. PATIENTS AND METHODS: Two groups of patients were studied.
      Group A (n = 24) received parenchymal suture, whereas Group B (n = 20) received
      parenchymal suture with fibrin glue and collagen fleece. The two groups were
      similar in baseline characteristics. We evaluated patient age, size of the lesion
      at CT, operative time, ischemia time, and sealant technique in relation to blood
      loss, hospital stay, and hemorrhagic complications. RESULTS: No significant
      difference was observed in perioperative parameters (P > 0.05). The mean size of
      lesion was 3.3 +/- 1.2 (range 1-8 cm) for group A and 3.0 +/- 1.3 (range 2-5 cm)
      for Group B. The mean operative time was 116 +/- 26.6 minutes (range 90-220
      minutes) for group A and 130 +/- 23.5 minutes (range 90-210 minutes) for group B.
      The mean warm ischemia time was 28.8 +/- 5.7 minutes (range 18-60) minutes) and
      35.6 +/- 6.2 minutes (range 20-52 minutes), respectively. The mean blood loss was
      178 +/- 34.5 mL (range 50-400 ml) for group A and 219 +/- 44.6 mL (range 80-750
      ml) for group B. The mean hospital stay was 5.9 +/- 1.2 days (range 5-8 days) for
      group A and 6.3 +/- 2.1 days (range 5-9 days) for group B. Four and two
      postoperative hemorrhage complications were observed in groups A and B,
      respectively. CONCLUSION: The use of fibrin glues and collagen fleece should be
      considered an adjuvant, as it does not present any substantial advantages, the
      suture being the key point in hemostasis control. We believe that in order to
      improve hemostasis, the efficacy of other types of sealants should be studied, as
      we were not convinced by those we used.

PMID- 17451337
TI  - Hand-assisted laparoscopic radical nephrectomy: comparison with conventional open
      radical nephrectomy.
AB  - PURPOSE: To compare the outcomes of hand-assisted laparoscopic radical
      nephrectomy (HALRN) with those of open radical nephrectomy (ORN) for renal-cell
      carcinoma (RCC). PATIENTS AND METHODS: A total of 130 patients with stage T(1) or
      T(2) RCC with a maximum diameter < 10 cm underwent radical nephrectomy by HALRN
      (n = 63) or ORN (n = 67). Data from these two groups were reviewed
      retrospectively. RESULTS: Although the maximum tumor size treated by HALRN was
      significantly less than that treated by ORN, there were no significant
      differences in the remaining features of the two groups. One HALRN was converted
      to open surgery. The mean operative time for HALRN (273 minutes) was
      significantly longer than that for ORN (189 minutes), whereas the mean estimated
      blood loss (315 v 381 mL). There were significant differences in measures of
      postoperative recovery, including time to walking (1.4 days for HALRN v 2.2 days
      for ORN), time to oral intake (1.8 v 3.3 days), and time to grant of permission
      for hospital discharge (7.4 v 10.2 days). Postoperative complications were
      observed in one and four patients in the HALRN and ORN groups, respectively.
      There were no significant differences in the recurrence-free and cancer-specific
      survival rates in the two groups. CONCLUSIONS: Despite the longer operative time,
      HALRN represents an effective, safe, and less-invasive treatment option for RCC.
      If performed for the proper indications, HALRN could achieve cancer control
      similar to that available with ORN.

PMID- 17451338
TI  - Combined treatment of iatrogenic rectourethral fistula with endoscopic fibrin
      glue application and clipping.
AB  - Rectourethral fistula (RUF) formation is a rare complication of prostatic surgery
      and other pelvic surgical procedures. The results of operations to correct RUF
      are not always satisfying, with a particular risk of recurrent breakdown or
      stricture formation at the site of the urethral closure. We present a case of a
      small RUF treated videoendoscopically with fibrin-glue application combined with
      endoscopic clipping.

PMID- 17451339
TI  - Laparoscopic retroperitoneal nephrectomy for giant hydronephrosis: when simple
      nephrectomy isn't simple.
AB  - BACKGROUND AND PURPOSE: Retroperitoneoscopic nephrectomy (RN) for giant
      hydronephrosis (GH) is regarded as a more challenging procedure than RN for small
      nonfunctioning kidneys (SNFK). We describe specific technical modifications to
      facilitate surgery in the GH group and compare outcomes in the two groups.
      PATIENTS AND METHODS: Data were collected in a prospective fashion on all
      patients undergoing upper urinary-tract laparoscopy at a single institution.
      Eleven patients (eight women, three men; mean age 41 years) underwent RN for GH.
      The etiologies were congenital ureteropelvic junction obstruction in 10 and
      obstruction secondary to endometriosis in 1. Technical modifications to
      facilitate surgery included initial fingerplasty, balloon dissection in two
      directions, initial intact dissection, subsequent pelvic puncture and aspiration,
      and extracorporeal retraction if required. The results were compared with those
      of a matched group of 19 patients who had RN for SNFK. RESULTS: All procedures
      were completed without open conversion. In the GH group, the mean operating time
      was 126 minutes (range 65-240 minutes) and the estimated blood loss 101 mL (range
      5-450 mL). No patient required transfusion, and the mean length of the hospital
      stay was 2.9 days (range 1.5-6 days). In the group undergoing RN for SNFK, the
      mean operating time was 116 minutes (range 55-270 minutes), the estimated blood
      loss 46 mL (range 5-400 mL), and the mean length of stay 2.8 days (range 1-5
      days). In the GH group, the estimated blood loss was significantly greater (P =
      0.042), and the operative time was longer, although this difference did not reach
      statistical significance. CONCLUSION: An RN for GH is not as simple as
      laparoscopic simple nephrectomy for other benign lesions. Operative duration and
      blood loss are greater. Technical modifications have been vital to our success
      with this procedure.

PMID- 17451340
TI  - Robotic radical prostatectomy learning curve of a fellowship-trained laparoscopic
      surgeon.
AB  - BACKGROUND AND PURPOSE: Several experienced practitioners of open surgery with
      limited or no laparoscopic background have adopted robot-assisted laparoscopic
      radical prostatectomy (RLRP) as an alternative to open radical prostatectomy
      (RRP), demonstrating outcomes comparable to those in large RRP and laparoscopic
      prostatectomy series. Thus, the significance of prior laparoscopic skills seems
      unclear. The learning curve, with respect to operative time and complications, in
      the hands of a devoted laparoscopic surgeon has not been critically assessed. We
      evaluated the learning curve of a highly experienced laparoscopic surgeon in
      achieving expertise with RLRP. PATIENTS AND METHODS: We prospectively evaluated
      150 consecutive patients undergoing RLRP by a single surgeon between March 2003
      and September 2005. The first 25 cases were performed with the assistance of a
      surgeon experienced in open RRP. Data were compared for the first, second, and
      third groups of 50 cases. Demographic data were similar for the three groups.
      Urinary and sexual function data were evaluated subjectively and objectively
      using the RAND-36v2 Survey and the UCLA PCI preoperatively and at 3, 6, and 12
      months postoperatively. RESULTS: The mean operative time, blood loss, and
      conversion rate decreased significantly with increasing experience. All open
      conversions occurred during the first 25 cases. Intraoperative and postoperative
      complication rates were similar among groups. Although the differences were not
      significant, urinary and sexual function recovery improved with experience.
      CONCLUSION: The RLRP learning curve for a fellowship-trained laparoscopic surgeon
      seems to be similar to that of laparoscopically naive yet experienced
      practitioners of open RRP. The RLRP is safe and reproducible and even during the
      learning curve can produce results similar to those reported in large RRP series.
      The importance of assistance by an experienced open RRP surgeon during the
      learning curve cannot be overemphasized.

PMID- 17451342
TI  - Introduction of non-B subtypes among Spaniards newly diagnosed with HIV type 1 in
      the Canary Islands.
AB  - The Spanish Canary Islands face the northwest coast of Africa, being one gate of
      entrance of African immigrants into Europe and of HIV-1 non-B strains, prevalent
      in most African regions. The presence and nature of HIV-1 non-B subtypes were
      examined in Spanish natives newly diagnosed with HIV-1 infection from 1998 to
      2004 in a reference hospital located in one of the largest islands of the
      archipelago. Subtyping of HIV-1 pol genes was performed in 139 out of 429
      individuals found to be HIV-1 positive during that period. Non-B strains infected
      40 (28.8%) subjects, 12 (13.7%) out of 87 native Spaniards and 28 (53.8%) out of
      52 immigrants (75% Africans) (p < 0.01). HIV-1 non-B subtypes, mostly recombinant
      forms, were present in Spaniards at least since 1998. HIV-1 non-B subtypes are
      frequently recognized in HIV+ Africans arriving in the Canary islands and
      continuously introduced into the newly diagnosed HIV-1+ native population living
      in the archipelago.

PMID- 17451343
TI  - Maintenance of HIV-specific central and effector memory CD4 and CD8 T cells
      requires antigen persistence.
AB  - The HIV-specific central and effector CD4 and CD8 memory T cell populations
      disappear from the peripheral blood of infected individuals under highly active
      antiretroviral therapy (HAART) with a mean half-life of 6.0 and 7.7 months,
      respectively. By contrast, cytomegalovirus (CMV)-specific responses are stable or
      increase. The striking quantitative differences between T cell memory to two
      persistent viral infections are instructive as to how antigen dosage contributes
      to the maintenance of antigen-specific memory T cell responses in humans.

PMID- 17451344
TI  - HyperPack: a software package for the study of levels, contexts, and patterns of
      APOBEC-mediated hypermutation in HIV.
AB  - G-to-A hypermutation, a massive substitution of G for A, was first observed in
      HIV genomes 15 years ago. Initially ascribed to fluctuating nucleotide pools or
      PCR errors, it has now been recognized as the result of an important host-defense
      mechanism mediated by APOBECs, a family of sequence-specific cytidine deaminases.
      Levels of hypermutation vary, and APOBECs have different preferences for the
      sequence context of cytidines targeted for deamination; analysis of hypermutation
      provides important information about the host-virus interaction during viral
      replication. Here we present HyperPack, a software package to support systematic
      characterization of hypermutated sequences. Users can define the context of
      substitution for independent study of the effects of different APOBECs. The
      SubstrateScan and HyperScan modules are overlapping sliding-window strategies to
      analyze the distribution of targeted motifs and their substitution levels,
      respectively, across the viral genome. HyperPack is a platform-flexible, Java
      stand-alone application available through http://www.hivresearch.org/hyperpack/.

PMID- 17451345
TI  - Natural variability in the HR-1 and HR-2 domains of HIV type 1 gp41 from
      different clades circulating in Italy.
AB  - The human immunodeficiency virus type 1 (HIV-1) HR-1 and HR-2 gp41 regions were
      sequenced in a total of 228 plasma or peripheral blood mononuclear cell samples
      obtained from an equal number of enfuvirtide-naive subjects for pol genotypic
      resistance testing in clinical practice. Phylogenetic analysis of the env
      sequences indicated that 102 belonged to subtype B and 95 to non-B subtypes (31
      CRF02_AG, 21 F1, 14 C, 11 A1/A2/A3, 9 CRF01_AE, 9 others) while the remaining 31
      were unique recombinant forms. There was considerable variability in the
      consensus sequence of different clades, particularly in HR-2. The HR-1 amino acid
      region 36-45, containing all of the enfuvirtide resistance mutations so far
      characterized, was well conserved except for position 42 where serine and
      asparagine were unevenly distributed in different subtypes. Enfuvirtide
      resistance mutations were not present in any sample, reinforcing the expectation
      that enfuvirtide is effective against many different HIV-1 clades and
      recombinants. However, some of the mutations outside the amino acid 36-45 region
      and provisionally suggested to play a role in modulating resistance were detected
      in a minority of cases. Molecular epidemiological surveys coupled with long-term
      observation of in vivo response to enfuvirtide and future fusion inhibitors are
      required to clarify the clinical significance of gp41 natural variability.

PMID- 17451346
TI  - Molecular epidemiology of HIV type 1 in treatment-naive patients in north
      Ethiopia.
AB  - To understand the predominant HIV subtype and drug-resistant viruses in northwest
      Ethiopia, isolates from 92 antiretroviral drug-naive HIV-1-infected tuberculosis
      patients were analyzed. Of these patients, 90 (97.8%) were found to be infected
      with viral subtype C. Other isolates had subtype A (1.1%) and subtype D (1.1%).
      No primary mutations were associated with protease inhibitor drug resistance. One
      case (1.1%) had the reverse-transcriptase mutation, V75I. Two patients (2.2%) had
      the G190A mutation, which confers resistance to the nonnucleoside reverse
      transcriptase inhibitor, nevirapine. Our study demonstrates that subtype C is the
      major HIV-1 subtype in northwest Ethiopia. Our results also reveal that the
      population in the study area had been exposed to antiretrovirals and that
      treatment-naive patients had drug resistance mutations. Thus, our results
      emphasize the need for routine drug resistance monitoring in northwest Ethiopia.

PMID- 17451347
TI  - Genetic characterization of CRF01_AE full-length human immunodeficiency virus
      type 1 sequences from Fujian, China.
AB  - HIV-1 CRF01_AE is the main prevalent HIV-1 recombinant strain in China and the
      dominant strain in Fujian as well; therefore, obtaining and understanding the
      genetic characterization of this clade become important. To date only a few full
      length HIV-1 CRF01_AE genomes from China have been sequenced. We reported 13 full
      length HIV-1 CRF01_AE isolate sequences from Fujian, China. DNA was extracted,
      the 5' and 3' halves of each genome were separately amplified, and the PCR
      products were cloned and sequenced. The phylogenetic analysis of the 13 sequences
      showed that they clustered with HIV-1 CRF01_AE isolates; these isolates were
      separated into a few distinct subgroups and were dispersed among the Thailand
      isolates, and the intersample diversity among Fujian isolates was significantly
      high. The high gene diversity among Fujian HIV-1 CRF01_AE isolates indicates that
      the HIV-1 CRF01_AE viruses in Fujian may be transmitted from multiple
      introductions. The work is essential for the design and development of an
      effective AIDS vaccine for China.

PMID- 17451351
TI  - Immunization with UV-induced apoptotic cells generates monoclonal antibodies
      against proteins differentially expressed in hepatocellular carcinoma cell lines.
AB  - Early and differential diagnosis of hepatocellular carcinoma (HCC) requires
      sensitive and specific tissue and serum markers. On the other hand, proteins
      involved in tumorigenesis are extensively modulated on exposure to apoptotic
      stimuli, including ultraviolet (UVC) irradiation. Hence, we generated monoclonal
      antibodies by using UVC-irradiated apoptotic cells of an HCC cell line, HUH7,
      aiming to explore proteins differentially expressed in tumors and apoptosis. We
      obtained 18 hybridoma clones recognizing protein targets in apoptotic HUH7 cells,
      and clone 6D5 was chosen for characterization studies because of its strong
      reactivity in cell-ELISA assay. Subtype of the antibody was IgG3 (kappa). Targets
      of 6D5 antibody were found to be abundantly expressed in all HCC cell lines
      except FLC4, which resembles normal hepatocytes. We also observed the secretion
      of 6D5 ligands by some of the HCC cell lines. Moreover, cellular proteins
      recognized by the antibody displayed a late upregulation in UVC-induced apoptotic
      cells. We concluded that 6D5 target proteins are modulated in liver tumorigenesis
      and apoptotic processes. We therefore propose the validation of our antibody in
      tissue and serum samples of HCC patients to assess its potential use for the
      early diagnosis of HCC and to understand the role of 6D5 ligands in liver
      carcinogenesis.

PMID- 17451348
TI  - High frequency of defective vpu compared with tat and rev genes in brain from
      patients with HIV type 1-associated dementia.
AB  - Human immunodeficiency virus type 1 (HIV) infection of the central nervous system
      frequently causes HIV-associated dementia (HAD) and other neurological disorders.
      The role of HIV regulatory and accessory proteins in the pathogenesis of these
      disorders is unclear. Here we analyzed sequences of tat, rev, and vpu genes in 55
      subgenomic clones previously shown to encode functional env genes from brain and
      lymphoid tissues of four AIDS patients with HAD. Phylogenetic analysis showed
      distinct compartmentalization of tat, rev, and vpu genes in brain versus lymphoid
      tissues. Nine of 19 vpu sequences from brain of two patients had premature stop
      codons at positions between amino acids 2 and 30, compared with 0 of 8 from
      lymphoid tissues. Tat sequences from brain (n = 8 of 8) but not lymphoid (n = 0
      of 6) tissue from one patient had a 35 amino acid truncation at the C-terminus.
      Rev sequences from the brain of one patient (n = 6 of 8) had a 5 amino acid
      truncation. These results demonstrate a high frequency of defective vpu compared
      with tat and rev genes in brain from HAD patients, and identify sequence variants
      of these regulatory/accessory genes that may influence the pathogenesis of HIV
      associated neurological disease.

PMID- 17451352
TI  - Development and identification of monoclonal antibodies against meso-Tetra
      (alpha,alpha,alpha,alpha,-O-phenylacetamide benzene) porphyrin.
AB  - The small molecule meso-Tetra (alpha,alpha,alpha,alpha-o-phenylacetamide benzene)
      porphyrin was synthesized through the condensation of o-nitrobenzaldehyde and
      pyrrole followed by reduction of the meso-tetra (o-nitrophenyl) porphyrin. The
      small molecule, without carrier, was used as complete antigen to immunize BALB/ C
      mice. Spleen cells producing high titer antibody were removed and fused with
      myeloma cells of SP2/0 origin. Using a conventional immunization protocol, stable
      murine monoclonal antibodies (MAbs) producing cell lines to meso-Tetra
      (alpha,alpha,alpha,alpha-o-phenylacetamide benzene) porphyrin 1F2 were obtained.
      Subclass determination showed that the clones produce IgG2a types of MAbs. The
      analytical results of HPLC and MALDI/TOFMS suggest that the purity of MAb 1F2 is
      100%, and MAb 1F2 has a relative molecular weight of 156678.8 Da. Our results
      demonstrated that small molecule meso-Tetra (alpha,alpha,alpha,alpha-o
      phenylacetamide benzene) porphyrin, as semiantigen without carrier, can elicit
      the formation of MAbs.

PMID- 17451353
TI  - B7 and 34B7 monoclonal antibodies: a theoretical approach to the molecular basis
      of immunoglobulin cross-reactive antibodies.
AB  - Neonatal natural antibodies (NAbs) are characterized by their high degree of
      idiotypic cross reactivity, together with some restrictions in the genetic
      mechanisms of variable region diversity. We report here the immunogenetic
      analysis of two anti-idiotype antibodies (B7 and 34B7 monoclonal antibodies
      [MAbs]), which are also polyreactive as NAbs. Evidence of a process of somatic
      mutations were found for heavy and light chain variable regions of both
      antibodies. A phylogenetic analysis of the V(H)J558 family showed that the
      immunoglobulin cross-reactivity displayed by B7 and 34B7 MAbs is not restricted
      to a particular subgroup of this family. Moreover, we identified amino acid
      motifs in the CDR H1 and H2 of B7 and 34B7 MAbs that are also present in high
      proportion in immunoglobulin cross-reactive antibodies (ICRA) reported in the
      Kabat database. We propose that these regions are involved in ICRA activity.

PMID- 17451354
TI  - Generation of rat monoclonal antibodies against murine PTA1/CD226.
AB  - PTA1 (platelet and T cell antigen 1), designated as CD226, is one of the major
      activating receptors on NK cells. PTA1/CD226 is also broadly expressed on a
      variety of hematopoietic cells, including Th cells, CTLs, NK T cells, monocytes,
      DCs, and mast cells, and is involved in multiple immunoregulation. Murine PTA1
      (mPTA1) is the homolog molecule of human PTA1. Using mPTA1-Fc as immunogen and
      the technique of rat B lymphocyte hybridoma, we raised five hybridoma cell lines
      secreting monoclonal antibodies (MAbs) to mPTA1, designated FMU-mCD226.1
      approximately FMU-mCD226.5. Rat immunoglobulin class and subclass of the MAbs FMU
      mCD226.1 approximately 5 were determined to be IgG2a, IgM, IgM, IgG1, and IgG1,
      respectively. FMU-mCD226.2, 3, 4, and 5 worked well in Western blot assay and
      could also recognize natural PTA1 on the surface of EL-4 cells and mPTA1 cDNA
      transfected 293T cells detected by FCM. Thus, successful production of rat anti
      murine PTA1/CD226 monoclonal antibodies provides a new powerful tool for
      investigation of murine PTA1 function in the mouse model, both in vitro and in
      vivo.

PMID- 17451355
TI  - Generation and characterization of monoclonal antibodies specific for human
      FCRLA.
AB  - FCRLA is a recently identified intracellular protein structurally related to the
      classic Fc receptors and expressed primarily in the germinal centers of B cells.
      We generated six monoclonal antibodies (MAbs) specific to the human protein. The
      MAbs recognize three different epitopes, which were shown to be localized on the
      D3 domain of the FCRLA molecule. The clones M101 and M616 were demonstrated to be
      applicable in various immunochemical analyses, such as immunoblotting,
      immunohistochemistry, and immunoprecipitation. In addition, this pair of
      antibodies was used for development of a sandwich version of ELISA to
      quantitatively detect FCRLA in cell lysates. Using these MAbs, we studied FCRLA
      expression in a panel of human B cell lines, such as Raji, Daudi, Bjab, BL-2,
      RPMI 1788, RPMI 8226, IM-9, and SKW6.4. It was found that all these lines, except
      RPMI 8226, produce FCRLA but may vary in the proportion of FCRLA-positive cells.
      The MAbs we established can be a useful tool to investigate the functional role
      of FCRLA and its applicability as a B cell development and malignant
      transformation marker.

PMID- 17451356
TI  - Generation of a new monoclonal antibody against MALT1 by genetic immunization.
AB  - Genetic immunization (GI), which is primarily used for vaccine purposes, is a
      method for producing antibodies to a protein by delivering the gene encoding the
      protein as a eukaryotic expression vector instead of the protein itself. The
      mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) is one of
      the most likely candidates for involvement in pathogenesis of MALT lymphoma and
      probably of multiple myelomas. In the present work we describe the production and
      characterization of a mouse monoclonal antibody (mAb) directed against MALT1 and
      the study of MALT1 protein expression in a large series of lymphomas and myeloma
      cell lines. The full-length coding sequence of human MALT1 was inserted into
      pcDNA3 vector and delivered into mouse skin using a helium gene gun. Six new mAbs
      against the MALT1 molecule were produced. In order to characterize and confirm
      the specificity of these mAbs, Western blot (WB) and immunoprecipitation (IP)
      analyses were performed. A new anti-MALT1 mAb was selected and tested in a large
      series of cell lines. These results confirm that GI is a reliable and effective
      alternative method for production of mAbs, allowing accurate and sensitive
      detection and screening of proteins by WB.

PMID- 17451357
TI  - Rapid and efficient preparation of monoclonal antibodies against 35 kDa
      lipoprotein of Mycoplasma penetrans.
AB  - To develop a rapid and efficient method for preparing monoclonal antibodies (MAb)
      against 35 kDa lipoprotein of Mycoplasma penetrans, BALB/c mice were injected
      into the footpads for immunization, and the popliteal lymph nodes were isolated
      19 days later for MAb-producing hybridomas, from which the mAbs against the 35
      kDa lipoprotein were screened. The identification of the mAb against the 35 kDa
      lipoprotein was performed using indirect enzyme-linked immunosorbent assay
      (ELISA) and immunoblotting. Using popliteal lymph node procedures, we generated
      several positive clones, one of which we characterized by ELISA and immunoblot.
      The clone 1D41B8 was identified as the immunoglobulin G1 (IgG1) isotype, kappa
      chain with affinity constants (Ka) of 2.95 x 10(9) M(-1). The MAbs did not cross
      react with a number of control bacteria, which included Mycoplasma fermentans,
      Mycoplasma hominis, and Mycoplasma genitalium. This is the first report on the
      preparation of mAbs against M. penetrans that is specific to 35 kDa lipoprotein
      using popliteal lymph nodes. The high-specificity and high-affinity MAbs produced
      by two methodologies used of hybridomas provide a basis for further research on
      the pathogenesis and early diagnosis of M. penetrans. This simple approach may
      become a method of choice for the generation and production of MAbs in a short
      period of time.

PMID- 17451358
TI  - Production and characterization of a monoclonal antibody to Francisella
      tularensis lipopolysaccharide.
AB  - Having the capacity to detect and identify pathogens that can be employed in a
      bioterror attack is critical from both a public health and defence perspective.
      Immunodiagnostic assays are useful tools for enhancing such detection
      capabilities. In order to develop an immunodiagnostic assay for the detection of
      Francisella tularensis, a murine monoclonal antibody (MAb) was developed, using
      the live vaccine strain (LVS) of F. tularensis as the inoculating antigen. A
      single MAb, F94G2-1, which is specific for the lipopolysaccharide (LPS) of this
      bacterium was developed and characterized. An indirect ELISA using purified LPS
      was effective in determining reactivity of the MAb against its target. An
      immunodotblot and a manually printed antigen microarray were also tested as
      suitable detection methods. Both assays showed that MAb F94G2-1 has excellent
      specificity for F. tularensis LPS and demonstrate the utility of using the same
      MAb in a variety of immunodiagnostic applications.

PMID- 17451359
TI  - Effectiveness of a mycoplasma elimination reagent on a mycoplasma-contaminated
      hybridoma cell line.
AB  - Mycoplasma contamination in cell culture is a frequently occurring serious
      limitation to biomedical research, particularly when it affects the irreplaceable
      cell lines. Although there are few reports of its successful elimination through
      rigorous protocols, it is the usual practice to destroy the infected cultures.
      Lately, a physical method using a mycoplasma-eliminating surfactin was described
      to effectively eliminate mycoplasma contamination from infected cell lines upon
      single use. We made an attempt using surfactin, an anti-mycoplasma biosurfactant,
      to eliminate mycoplasma from an extensively infected irreplaceable hybridoma cell
      line. There were apparent indications of limited elimination, suggesting the
      possible usefulness of surfactin in achieving total decontamination. However, it
      was observed that surfactin was toxic to the infected hybridoma cells plated at
      various cell densities and exposure times. It is suggested that preliminary tests
      should be performed to determine the cytotoxicity of surfactin with sufficient
      back-ups of the contaminated cell culture before decontamination is attempted.
      Additionally, possible ways to enhance its effectiveness are discussed.

PMID- 17451368
TI  - Cnot7-null mice exhibit high bone mass phenotype and modulation of BMP actions.
AB  - Cnot7 is a recently identified regulator of spermatogenesis in adult mice.
      Because Cnot7 binds to Tob, a BMP inhibitor shown to be involved in bone
      metabolism, we examined whether Cnot7 is involved in bone mass regulation by
      using adult Cnot7 deficient mice. Cnot7-/- mice exhibited a high bone mass
      phenotype. This was associated with an increase in bone formation rate but not
      with any alteration in bone resorption parameters. On BMP treatment, Cnot7-/-
      cells expressed higher levels of alkaline phosphatase compared with control
      cells. Direct BMP2 injection induced larger bone mass in Cnot7-/- calvaria than
      control in vivo. These observations revealed that Cnot7 is an endogenous
      suppressor of bone mass and inhibits BMP actions in osteoblasts. INTRODUCTION:
      The molecular mechanisms involved in the determination of bone mass have been
      gradually understood based on recent analyses. Cnot7 (Ccr4-Not complex 7) is a
      component of transcriptional Ccr4-Not complex, is conserved from yeast to human,
      and binds to Tob, but its function in bone is not understood. MATERIALS AND
      METHODS: To elucidate the role of involvement of Cnot7 in bone mass
      determination, we examined the bone of adult male Cnot7-null and heterozygous
      mice based on microCT analyses, histomorphometry, cell cultures, and in vivo BMP
      assays. RESULTS: Cnot7-/- mice showed an increase in bone mass levels by >50%
      compared with controls. Analyses of the histomorphometric parameters indicated
      that bone formation activity in Cnot7-/- mice was enhanced, whereas bone
      resorption activity was not altered. These effects on osteoblasts were cell
      autonomous because mineralized nodule formation was enhanced in the cultures of
      bone marrow cells prepared from Cnot7-/- mice. In vitro analyses to elucidate
      Cnot7 effects revealed that BMP-induced expression of alkaline phosphatase in
      Cnot7-/- calvaria-derived osteoblastic cells was enhanced compared with controls.
      Moreover, BMP injection-induced new bone formation in vivo was enhanced in Cnot7
      /- mice. CONCLUSIONS: These observations indicated that Cnot7 is an endogenous
      suppressor of bone mass in adult mice and inhibits BMP actions.

PMID- 17451369
TI  - Increases in BMD correlate with improvements in bone microarchitecture with
      teriparatide treatment in postmenopausal women with osteoporosis.
AB  - Increases in BMD are correlated with improvements in 2D and 3D trabecular
      microarchitecture indices with teriparatide treatment. Therefore, improvements in
      trabecular bone microarchitecture may be one of the mechanisms to explain how BMD
      increases improve bone strength during teriparatide treatment. INTRODUCTION: Bone
      strength is determined by BMD and other elements of bone quality, including bone
      microarchitecture. Teriparatide treatment increases BMD and improves both
      cortical and trabecular bone microarchitecture. Increases in lumbar spine (LS)
      BMD account for approximately 30-41% of the vertebral fracture risk reduction
      with teriparatide treatment. The relationship between increases in BMD and
      improvements in cortical and trabecular microarchitecture has not yet been
      studied. MATERIALS AND METHODS: The relationship between increases in BMD and
      improvements in cortical and trabecular microarchitecture after teriparatide
      treatment was assessed using data from a subset of patients who had areal BMD
      measurements and structural parameters from transiliac bone biopsies in the
      Fracture Prevention Trial. 2D histomorphometric and 3D microCT parameters were
      measured at baseline and 12 (n = 21) or 22 (n = 36) mo. LS BMD was assessed at
      baseline and 12 and 18 mo, and femoral neck (FN) BMD was measured at baseline and
      12 mo. Pearson correlation was performed to assess the relationship between
      actual changes in BMD and actual changes in microarchitectural parameters.
      RESULTS: Changes in LS BMD at 12 mo were significantly correlated with
      improvements in trabecular bone structure at 22 mo: 2D bone volume (r = 0.45, p =
      0.02), 2D mean wall thickness (r = 0.41, p = 0.03), 3D bone volume (r = 0.48, p =
      0.006), 3D trabecular thickness (r = 0.44, p = 0.01), 3D trabecular separation (r
      = -0.37, p = 0.04), 3D structural model index (r = -0.54, p = 0.001), and 3D
      connectivity density (r = 0.41, p = 0.02). Changes in LS BMD at 18 mo had similar
      correlations with improvements in bone structure at 22 mo. Changes in FN BMD at
      12 mo were significantly correlated with changes in 2D mean wall thickness (r =
      0.56, p = 0.002), 3D bone volume (r = 0.51, p = 0.004), 3D trabecular thickness
      (r = 0.44, p = 0.01), 3D trabecular separation (r = -0.46, p = 0.01), and 3D
      structural model index (r = -0.55, p = 0.001). CONCLUSIONS: Increases in BMD are
      correlated with improvements in trabecular microarchitecture in iliac crest of
      patients with teriparatide treatment. Therefore, improvements in trabecular bone
      microarchitecture may be one of the mechanisms to explain how BMD increases
      improve bone strength during teriparatide treatment.

PMID- 17451370
TI  - Bone healing and migration of cord blood-derived stem cells into a critical size
      femoral defect after xenotransplantation.
AB  - Stem cell and tissue engineering-based therapies have become a promising option
      to heal bony defects in the future. Human cord blood-derived mesenchymal stem
      cells were seeded onto a collagen/tricalcium phosphate scaffold and
      xenotransplanted into critical size femoral defects of 46 nude rats. We found a
      survival of human cells within the scaffold and surrounding bone/bone marrow up
      to 4 wk after transplantation and an increased bone healing rate compared with
      controls without stem cells. This study supports the application of cord blood
      stem cells for bone regeneration. INTRODUCTION: The treatment of critical size
      bone defects is still a challenging problem in orthopedics. In this study, the
      survival, migration, and bone healing promoting potency of cord blood-derived
      stem cells were elucidated after xenotransplantation into a critical size femoral
      defect in athymic nude rats. MATERIALS AND METHODS: Unrestricted somatic stem
      cells (USSCs) isolated from human cord blood were tested toward their mesenchymal
      in vitro potency and cultivated onto a collagen I/III and beta-tricalcium
      phosphate (beta-TCP) scaffold. The biomaterial-USSC composite was transplanted
      into a 4-mm femoral defect of 40 nude rats and stabilized by an external fixator.
      Twelve animals without USSCs served as controls. Cell survival, migration, and
      bone formation were evaluated by blood samples, X-rays, and histological and
      immunocytochemical analysis of different organs within a maximal postoperative
      follow-up of 10 wk. RESULTS: Of the 52 nude rats, 46 animals were evaluated (drop
      out rate: 11.5%). Human-derived stem cells showed an engraftment within the
      scaffold and adjacent femur up to 4 wk after xenotransplantation. With further
      time, the human cells were destroyed by the host organism. We found a significant
      increase in bone formation in the study group compared with controls. USSC
      transplantation did not significantly influence blood count or body weight in
      athymic nude rats. Whereas the collagen I/III scaffold was almost resorbed 10 wk
      after transplantation, there were still significant amounts of TCP present in
      transplantation sites at this time. CONCLUSIONS: Human cord blood-derived stem
      cells showed significant engraftment in bone marrow, survived within a collagen
      TCP scaffold up to 4 wk, and increased local bone formation in a nude rat's
      femoral defect.

PMID- 17451371
TI  - Aging reduces skeletal blood flow, endothelium-dependent vasodilation, and NO
      bioavailability in rats.
AB  - We determined whether aging diminishes bone blood flow and impairs endothelium
      dependent vasodilation. Femoral perfusion was lower in old animals, as well as
      endothelium-dependent vasodilation and NO bioavailability. These effects could
      contribute to old age-related bone loss and the increased risk of fracture.
      INTRODUCTION: Aging has been shown to diminish bone blood flow in rats and
      humans. The purpose of this study was to determine whether blood flow to regions
      of the femur perfused primarily through the principal nutrient artery (PNA) are
      diminished with aging and whether this putative reduction in flow is associated
      with impaired endothelium-dependent vasodilation. MATERIALS AND METHODS: Blood
      flow was measured in conscious young adult (4-6 mo old) and aged (24-26 mo old)
      male Fischer-344 rats using radiolabeled microspheres. Endothelium-dependent
      vasodilation of the PNA was assessed in vitro using acetylcholine (ACh), whereas
      the contribution of the NO synthase (NOS) and cyclooxygenase (COX) signaling
      pathways to endothelium-dependent vasodilation was determined using the NOS and
      COX inhibitors L-NAME and indomethacin, respectively. RESULTS: Femoral blood flow
      in the aged rats was 21% and 28% lower in the proximal and distal metaphyses,
      respectively, and 45% lower in the diaphyseal marrow. Endothelium-dependent
      vasodilation was reduced with old age (young: 83 +/- 6% maximal relaxation; aged:
      62 +/- 5% maximal relaxation), whereas endothelium-independent vasodilation
      (sodium nitroprusside) was unaffected by age. The reduction in endothelium
      dependent vasodilation was mediated through impairment of the NOS signaling
      pathway, which resulted in lower NO bioavailability (young: 168 +/- 56 nM; aged:
      50 +/- 7 nM). CONCLUSIONS: These data show that reductions in metaphyseal bone
      and diaphyseal marrow perfusion with old age are associated with diminished
      endothelium-dependent vasodilation through an impairment of the NOS mechanism.
      Such age-related changes in bone perfusion and vascular NO signaling could impact
      clinical bone loss, increase risk of fracture, and impair fracture healing in the
      elderly.

PMID- 17451372
TI  - Association between physical activity and BMD in young men is modulated by
      catechol-O-methyltransferase (COMT) genotype: the GOOD study.
AB  - In this large population-based study in young men, we show that the COMT
      val158met polymorphism modulates the association between physical activity, aBMD
      (DXA), and trabecular vBMD (pQCT). INTRODUCTION: Peak BMD is an important
      predictor of future risk of osteoporosis and is largely determined by genetic
      factors but also by environmental factors, among which physical activity (PA) is
      a strong contributor. Estrogens are believed to influence the mechanical strain
      signal generated by bones subjected to mechanical loading. Catechol-O
      methyltransferase (COMT) is involved in the degradation of estrogens. A
      functional polymorphism in the COMT gene (val158met), results in a 60-75%
      difference in enzyme activity between the val (high activity = H) and met (low
      activity = L) variants. The aim of this study was to determine if the COMT
      val158met polymorphism modulates the association between PA and BMD in young men.
      MATERIALS AND METHODS: The Gothenburg Osteoporosis and Obesity Determinants
      (GOOD) study consists of 1068 men (age, 18.9 +/- 0.6 yr). Areal BMD (aBMD) was
      measured by DXA, whereas cortical and trabecular volumetric BMD (vBMD) were
      measured by pQCT. Study subjects were genotyped and classified as COMT(LL),
      COMT(HL), or COMT(HH). The amount (h/wk) of PA was determined through
      questionnaires. RESULTS: Using a linear regression model (including age, height,
      weight, smoking, and calcium intake as covariates), significant interactions
      between the COMT genotype and PA were seen for aBMD at all sites and for
      trabecular vBMD in both the radius and the tibia. The difference in adjusted aBMD
      and trabecular vBMD between high (>or=4 h/wk) and low PA (<4 h/wk) was greater in
      COMT(LL) subjects than in subjects homozygous for the COMT(HH) (total body aBMD:
      COMT(LL) 4.2% versus COMT(HH) 1.5%, p = 0.02; lumbar spine aBMD: COMT(LL) 7.8%
      versus COMT(HH) 3.9%, p = 0.04; tibia trabecular vBMD: COMT(LL) 7.1% versus
      COMT(HH) 1.0%, p < 0.01). The COMT polymorphism was associated with aBMD, at all
      sites and with trabecular vBMD in the low-PA subjects, but not in their high-PA
      counterparts. CONCLUSIONS: We show that the COMT val158met polymorphism modulates
      the association between PA, aBMD, and trabecular vBMD, suggesting that this
      polymorphism is of importance for BMD in subjects with a low level of PA.

PMID- 17451373
TI  - LIF inhibits osteoblast differentiation at least in part by regulation of HAS2
      and its product hyaluronan.
AB  - LIF arrests osteogenesis in fetal rat calvaria cells in a differentiation stage
      specific manner. Differential display identified HAS2 as a LIF-induced gene and
      its product, HA, modulated osteoblast differentiation similarly to LIF. Our data
      suggest that LIF arrests osteoblast differentiation by altering HA content of the
      extracellular matrix. INTRODUCTION: Leukemia inhibitory factor (LIF) elicits both
      anabolic and catabolic effects on bone. We previously showed in the fetal rat
      calvaria (RC) cell system that LIF inhibits osteoblast differentiation at the
      late osteoprogenitor/early osteoblast stage. MATERIALS AND METHODS: To uncover
      potential molecular mediators of this inhibitory activity, we used a positive
      negative genome-wide differential display screen to identify LIF-induced changes
      in the developing osteoblast transcriptome. RESULTS: Although LIF signaling is
      active throughout the RC cell proliferation-differentiation sequence, only a
      relatively small number of genes, in several different functional clusters, are
      modulated by LIF specifically during the LIF-sensitive inhibitory time window.
      Based on their known and predicted functions, most of the LIF-regulated genes
      identified are plausible candidates to be involved in the LIF-induced arrest of
      osteoprogenitor differentiation. To test this hypothesis, we further analyzed the
      function of one of the genes identified, hyaluronan synthase 2 (HAS2), in the LIF
      induced inhibition. Synthesis of hyaluronan (HA), the product of HAS enzymatic
      activity, was stimulated by LIF and mimicked the HAS2 expression profile, with
      highest expression in early/proliferative and late/maturing cultures and lowest
      levels in intermediate/late osteoprogenitor-early osteoblast cultures.
      Exogenously added high molecular weight HA, the product of HAS2, dose-dependently
      inhibited osteoblast differentiation, with pulse-treatment effective in the same
      differentiation stage-specific inhibitory window as seen with LIF. In addition,
      however, pulse treatment with HA in early cultures slightly increased bone nodule
      formation. Treatment with hyaluronidase, on the other hand, stimulated bone
      nodule formation in early cultures but caused a small dose-dependent inhibition
      of osteoblast differentiation in the LIF- and HA-sensitive late time window.
      CONCLUSIONS: Together the data suggest that osteoblast differentiation is acutely
      sensitive to HA levels and that LIF inhibits osteoblast development at least in
      part by stimulating high molecular weight HA synthesis through HAS2.

PMID- 17451374
TI  - Natural history of hyperplastic callus formation in osteogenesis imperfecta type
      V.
AB  - Hyperplastic callus formation was assessed in 23 patients with osteogenesis
      imperfecta type V. Hyperplastic callus mostly affected long bones in the lower
      extremities and occurred predominantly during phases of rapid growth.
      INTRODUCTION: Hyperplastic callus (HPC) formation is one of the most conspicuous
      features of osteogenesis imperfecta (OI) type V, but the natural history of HPC
      has not been well characterized. MATERIALS AND METHODS: In this retrospective
      single-center study, we assessed HPC in 23 OI type V patients (9 females and 14
      males). RESULTS: Fifteen patients (65%) had HPC at 48 skeletal sites, 30 of which
      affected the lower limbs. The number of HPC sites per patient ranged from 0 to 7,
      with an average of 2.6 for men and 1.1 for women (p = 0.047 for this sex
      difference; t-test). New HPC formation was observed both after fractures and
      outside of the context of fractures. Only a minority of lower limb fractures
      (26%) precipitated HPC formation. After an initial enlargement phase, HPC lesions
      usually stabilized, but could also resolve completely (n = 2) or progress and
      lead to bone deformation. The most common complication of HPC was a fracture
      through the lesion (n = 7). Neither pamidronate nor indomethacin seemed to
      influence the course of HPC. CONCLUSIONS: HPC is a potentially serious
      complication of OI type V. Given the rarity of the disorder, treatment studies
      will require multicenter collaborations.

PMID- 17451375
TI  - Genetic dissection of mouse distal chromosome 1 reveals three linked BMD QTLs
      with sex-dependent regulation of bone phenotypes.
AB  - Genetic analyses with mouse congenic strains for distal Chr1 have identified
      three closely linked QTLs regulating femoral vBMD, mid-diaphyseal cortical
      thickness, and trabecular microstructure in a sex-dependent fashion. The
      homologous relationship between distal mouse Chr 1 and human 1q21-24 offers the
      possibility of finding common regulatory genes for cortical and trabecular bone.
      INTRODUCTION: The distal third of mouse chromosome 1 (Chr 1) has been shown to
      carry a major quantitative trait locus (QTL) for BMD from several inbred mouse
      strain crosses. Genetic and functional analyses are essential to identify genes
      and cellular mechanisms for acquisition of peak bone mass. MATERIALS AND METHODS:
      Nested congenic sublines of mice were developed with a C57BL/6J (B6) background
      carrying <1- to 9-Mbp-sized segments donated from C3H/HeJ (C3H). Isolated femurs
      from 16-wk-old female and male mice were measured by pQCT and microCT40 for
      volumetric (v)BMD, mid-diaphyseal cortical thickness, and distal trabecular
      phenotypes. Static and dynamic histomorphologic data were obtained on selected
      females and males at 16 wk. RESULTS AND CONCLUSIONS: We found that the original
      BMD QTL, Bmd5, mapped to distal Chr 1 consists of three QTLs with different
      effects on vBMD and trabecular bone in both sexes. Compared with B6 controls,
      femoral vBMD, BMD, and cortical thickness (p < 0.0001) were significantly
      increased in congenic subline females, but not in males, carrying C3H alleles at
      QTL-1. Both females and males carrying C3H alleles at QTL-1 showed marked
      increases in BV/TV by microCT compared with B6 mice (p < 0.0001). Females
      increased BV/TV by increasing trabecular thickness, whereas males increased
      trabecular number. In addition, the microCT40 data showed two unique QTLs for
      male trabecular bone, QTL-2 and QTL-3, which may interact to regulate trabecular
      thickness and number. These QTLs are closely linked with and proximal to QTL-1.
      The histomorphometric data revealed sex-specific differences in cellular and bone
      formation parameters. Mice and humans share genetic homology between distal mouse
      Chr 1 and human Chr 1q20-24 that is associated with adult human skeletal
      regulation. Sex- and compartment-specific regulatory QTLs in the mouse suggest
      the need to partition human data by sex to improve accuracy of mapping and
      genetic loci identification.

PMID- 17451377
TI  - Normative values, reliability and sample size estimates in heart rate
      variability.
AB  - HRV (heart rate variability) is a non-invasive maker of cardiac autonomic
      modulation utilized in many hundreds of scientific studies each year. The
      reliability of heart rate variability has been frequently investigated yet
      remains poorly quantified. Assessing the reliability of a measure that assesses
      dynamic physiological processes and shows large between- and within-subject
      variation is a complex task. In this issue of Clinical Science, Pinna and co
      workers provide excellent insight into the test-retest reliability of commonly
      used HRV indices and put the values obtained into context by comparing them with
      levels of between-subject variation and by producing sample size estimates.

PMID- 17451378
TI  - A dinoflagellate CDK5-like cyclin-dependent kinase.
AB  - BACKGROUND INFORMATION: Mitosis during the dinoflagellate cell cycle is unusual
      in that the nuclear envelope remains intact and segregation of the permanently
      condensed chromosomes uses a cytoplasmic mitotic spindle. To examine regulation
      of the dinoflagellate cell cycle in the context of these unusual nuclear
      features, it is necessary to isolate and characterize cell cycle regulators such
      as CDK (cyclin-dependent kinase). RESULTS: We report the characterization of a
      CDK from the dinoflagellate Lingulodinium polyedrum. This CDK reacts with an anti
      PSTAIRE antibody and was identified by protein microsequencing after partial
      purification. The protein microsequence shows homology toward the Pho85/CDK5
      clade of CDKs. Neither the amount nor the phosphorylation state changed over the
      course of the cell cycle, in agreement with results reported for CDK5 family
      members in other systems. CONCLUSIONS: We conclude we have probably isolated a
      dinoflagellate CDK5-like protein. The data reported here support the
      identification of this protein as a CDK5 homologue, and suggest that
      dinoflagellates may contain several CDK families.

PMID- 17451379
TI  - [Papillomavirus vaccines now allowed--ethical and logistical considerations].

PMID- 17451380
TI  - Shampoos: ingredients, efficacy and adverse effects.
AB  - Shampoos are the most frequently prescribed treatment for the hair and scalp. The
      different qualities demanded from a shampoo go beyond cleansing. A cosmetic
      benefit is expected, and the shampoo has to be tailored to variations associated
      with hair quality, age, hair care habits, and specific problems related to the
      condition of the scalp. The reciprocal relationship between cosmetic technology
      and medical therapy is reflected in the advances of shampoo formulation that has
      made applications possible that combine benefits of cosmetic hair care products
      with efficacy of medicinal products. A shampoo is composed of 10 to 30
      ingredients: cleansing agents (surfactants), conditioning agents, special care
      ingredients, and additives. Since the cleansing activity depends on the type and
      amount of surfactants utilized, shampoos are composed of a blend of different
      surfactants, depending on the requirements of the individual hair type.
      Development time from the concept to the commercial shampoo may take longer than
      a year. Much effort is invested in the development of conditioning agents, which
      impart luster, smoothness, volume and buoyancy. Another prerequisite is a scalp
      free of scaling. Current anti-dandruff agents primarily have an antimicrobial
      mode of action, and inhibit growth of Malassezia spp. Recent developments in
      shampoo technology have led to increased efficacy of anti-dandruff agents,
      allowing shorter contact time, and reducing irritation.

PMID- 17451381
TI  - Galenics of dermal products--vehicles, properties and drug release.
AB  - The efficiency, tolerability, and applicability of topical agents are directly
      related to employed vehicles. Thus to achieve optimum topical therapy, a solid
      knowledge of the vehicles, their composition, and their physical and dermato
      pharmacological actions are important. Common vehicles are complex mixtures
      consisting of diverse ingredients belonging to six major groups, i. e.
      hydrophilic and lipophilic bases, emulsifiers, gel-forming agents, preservatives,
      and antioxidants. This makes it possible to optimize both the cosmetic features
      and to adjust a vehicle to the properties of an incorporated drug and site of
      application. On the other hand it makes it difficult to make a proper choice
      between several alternatives or to use it in individual prescriptions. In order
      to simplify the selection of a formulation, it is useful to categorize them
      systemically into several groups, such as ointments, creams, gels, emulsions, and
      suspensions. Within these groups some general rules can be derived for the
      selection of a vehicle with respect to skin conditions and the application site.
      When active substances are incorporated into a base the dermato-biopharmaceutical
      properties of the whole system (drug + vehicle) also have to be considered. If
      for a given vehicle drug transport into the skin does not suffice, several
      methods are described to facilitate its penetration, such as by hydrating the
      skin or by adding chemical penetration enhancers.

PMID- 17451382
TI  - Examples for the importance of radiophysical measurements in clinical
      phototherapy.
AB  - BACKGROUND: Optimal UV therapy requires regular surveillance of the variables
      that influence therapeutic success. In daily practice, phototherapy equipment is
      often operated with an attitude of "autocontrol." This implies that thorough
      control measurements of the emission spectra and calibration of UV fluences are
      not routinely performed. For both quality control and patient safety, it is
      essential to regularly check whether a UV source is providing the right target
      spectrum with the correct dose to the skin. METHODS: We have exemplarily taken
      three UV sources currently used in clinical practice and performed radiophysical
      measurements, i. e. determined emission spectra, radiation output and correctness
      of dose calculation. RESULTS: All three sources revealed either a largely
      inhomogeneous distribution pattern of radiation intensity, variation of radiation
      intensity over time or insufficient filtering of the UV lamp emission spectrum.
      Furthermore the dose calculation procedures had to be revised because of
      significant differences between the estimated and the administered UV doses.
      CONCLUSIONS: Radiophysical measurement of all UV-equipment in clinical use is a
      simple and effective way to improve the safety and reliability of phototherapy.
      Such measurements help to uncover technical flaws in radiation sources and
      prevent unnecessary side effects and UV exposure risks for the patient.

PMID- 17451383
TI  - Comparison of the efficacy and safety of topical minoxidil and topical
      alfatradiol in the treatment of androgenetic alopecia in women.
AB  - BACKGROUND: Two drugs which are approved for the treatment of androgenetic
      alopecia in women in Germany were compared with regard to their influence on hair
      growth. PATIENTS AND METHODS: Patients were randomized to group I (n = 52) who
      used 2% minoxidil solution twice daily for a period of 12 months or to group II
      (n = 51) who used 0.025% alfatradiol solution once daily for 6 months and were
      then switched to 2% minoxidil solution for months 7-12. Changes in hair growth
      parameters were determined using the TrichoScan. RESULTS: Topical treatment with
      2% minoxidil solution for 6 months resulted in a significant increase of
      cumulative hair thickness (p < 0.0001) and absolute hair density (p < or =
      0.0025), whereas these parameters of hair growth remained nearly unchanged after
      6 months of treatment with alfatradiol solution. Evaluation of the same
      parameters from month 7 to month 12 demonstrated that 12 months minoxidil
      treatment resulted in an increasing stabilization (group I). After the
      alfatradiol-->minoxidil switch in group II a significant increase in cumulative
      hair thickness (p < 0.0001) and absolute hair density (p < 0.0001) was achieved.
      Both study medications were well tolerated. CONCLUSIONS: Treatment with minoxidil
      can induce an increase in hair density and hair thickness,whereas treatment with
      alfatradiol results in deceleration or stabilization of hair loss.

PMID- 17451384
TI  - Treatment of pustular psoriasis with infliximab.
AB  - Pustular psoriasis is a severe form of psoriasis with a generalized pustular
      eruption. Since TNF-alpha plays an important role in pustular psoriasis, we
      treated two patients who had not responded to established therapy regimens with
      the TNF-alpha antagonist infliximab. Both patients showed significant
      improvements of their skin eruption and their general condition within three days
      after treatment and without any side effects. We suggest that infliximab is a
      therapeutic option for severe therapy-resistant pustular psoriasis because a
      single well-tolerated dose significantly ameliorates the patient's condition.

PMID- 17451385
TI  - Hyalinosis cutis et mucosae.
AB  - Hyalinosis cutis et mucosae is a rare autosomal recessive disorder which is
      characterized by deposition of hyaline material around the basement membrane of
      the skin and mucous membranes. Typical clinical symptoms are hoarseness,
      infiltration of the mucous membranes and papular verrucous skin changes.
      Mutations within the extracellular matrix protein gene (ECM-1) are the underlying
      defect. We report on a 24-year-old man, who had first been seen in our department
      at the age of seven and had undergone the necessary diagnostic procedures and who
      revisited 17 years later with hoarseness and extensive verrucous skin changes at
      elbows and knees which were removed by excision. A new mutation of the ECM1 gene
      was identified.

PMID- 17451386
TI  - Lyme borreliosis--an update.
AB  - Lyme borreliosis is the most common tick-borne, infectious disease in the
      northern hemisphere. Disease manifestations in the United States and Europe vary
      as a result of geographic distribution of different species within the
      genospecies Borrelia burgdorferi sensu lato, which in turn are host-specific.
      Certain toxigenic B. burgdorferi strains cause early disseminated disease. The
      ability of Borrelial organisms to break down the extracellular matrix also
      promotes dissemination. B. burgdorferi are eliminated by complement-mediated
      lysis and by T and B cell activity of the specific immune response. Yet, B.
      burgdorferi can evade humoral immunity by means of type of protective mechanism
      by which it adheres to the proteoglycan decorin in the joints and skin. A further
      factor in the persistence of the pathogen is altered antigen expression. Re
      infection usually occurs with a different strain, although repeated infection
      with the same strain is also possible after a certain period of latency. New
      developments in serologic testing include the use of recombinant native antigen
      as well as antigens produced in vivo such as VlsE (variable major protein-like
      sequence, expressed) or decorin-binding protein A. Diagnosis continues to be
      complicated by seropositivity of healthy individuals, the persistence of
      antibodies after therapy, and a lacking humoral immune response in patients with
      erythema migrans.

PMID- 17451387
TI  - [Verruciform hyperkeratosis of the right lateral plantar foot].

PMID- 17451388
TI  - [Vacuum assisted wound closure on the scalp].

PMID- 17451389
TI  - [Three important rules in dermatoscopy].

PMID- 17451390
TI  - Scabies.

PMID- 17451391
TI  - [A portrait of a lady with vitilgo painted by Adolph von Menzels].

PMID- 17451392
TI  - [Reader's letter on Marcus Meissner, Jens, Gille, Roland Kaufmann. Calciphylaxis:
      no therapeutic concepts for a poorly understood syndrome?].

PMID- 17451395
TI  - [The Division of Dermatology in Viennese Neustadt celebration of its first year
      of existence].

PMID- 17451397
TI  - AUDIT-C as a brief screen for alcohol misuse in primary care.
AB  - BACKGROUND: The Alcohol Use Disorders Identification Test Consumption (AUDIT-C)
      questions have been previously validated as a 3-item screen for alcohol misuse
      and implemented nationwide in Veterans Affairs (VA) outpatient clinics. However,
      the AUDIT-C's validity and optimal screening threshold(s) in other clinical
      populations are unknown. METHODS: This cross-sectional validation study compared
      screening questionnaires with standardized interviews in 392 male and 927 female
      adult outpatients at an academic family practice clinic from 1993 to 1994. The
      AUDIT-C, full AUDIT, self-reported risky drinking, AUDIT question #3, and an
      augmented CAGE questionnaire were compared with an interview primary reference
      standard of alcohol misuse, defined as a Diagnostic and Statistical Manual, 4th
      ed. alcohol use disorder and/or drinking above recommended limits in the past
      year. RESULTS: Based on interviews with 92% of eligible patients, 128 (33%) men
      and 177 (19%) women met the criteria for alcohol misuse. Areas under the receiver
      operating characteristic curves (AUROCs) for the AUDIT-C were 0.94 (0.91, 0.96)
      and 0.90 (0.87, 0.93) in men and women, respectively (p=0.04). Based on AUROC
      curves, the AUDIT-C performed as well as the full AUDIT and significantly better
      than self-reported risky drinking, AUDIT question #3, or the augmented CAGE
      questionnaire (p-values <0.001). The AUDIT-C screening thresholds that
      simultaneously maximized sensitivity and specificity were > or =4 in men
      (sensitivity 0.86, specificity 0.89) and > or =3 in women (sensitivity 0.73,
      specificity 0.91). CONCLUSIONS: The AUDIT-C was an effective screening test for
      alcohol misuse in this primary care sample. Optimal screening thresholds for
      alcohol misuse among men (> or =4) and women (> or =3) were the same as in
      previously published VA studies.

PMID- 17451398
TI  - Ethanol acceptance is high during early infancy and becomes still higher after
      previous ethanol ingestion.
AB  - BACKGROUND: Infant (preweanling) rats readily accept ethanol without initiation
      procedures. During their second and third postnatal weeks, rats ingest large
      quantities of even high concentrations of ethanol. The present study tested the
      consequences of still earlier exposure to ethanol differing in concentration,
      mode of administration, and contextual circumstances. METHODS: Every 48 hours
      from postnatal day 2 (P2) to P10, pups were given access to 0, 5, 15, or 25%
      ethanol through an independent feeding procedure (consumption off the floor; COF)
      or by intragastric (i.g.) administration. The amount of ethanol consumed was
      matched for the 2 modes of ethanol delivery. On P12 pups were tested for intake
      of 15% ethanol through an intraoral infusion test or COF. RESULTS: Beginning on
      P6, pups ingested more ethanol solution than water, and by P8 and P10 they
      ingested large quantities of ethanol--1.5 to 2.0 g/kg ethanol from 15 or 25%
      ethanol solution within a 10-minute period. This early experience with ingestion
      of ethanol increased subsequent ethanol intake on P12, particularly when
      concentration and mode of ingestion were the same as before. CONCLUSIONS: Intake
      on P12 was increased by prior exposure to ethanol intragastrically as well as by
      the conventional oral route, suggesting pharmacological effects of prior ethanol
      exposure. Yet, the apparently greater influence of prior exposure by the oral
      route and the influence of prior ethanol concentration also implicate the
      importance of ethanol's chemosensory attributes for effects of prior ethanol
      exposure. The equivalent g/kg intake of ethanol in 15 or 25% solutions during the
      early part of the second postnatal week suggests that regulation of ethanol
      intake at P8 and P10 is similar to that observed previously in adults. Change in
      aspects of ethanol ingestion at about P6 may reflect the shift in function of the
      GABA system at about this age.

PMID- 17451399
TI  - Chronic smoking is associated with differential neurocognitive recovery in
      abstinent alcoholic patients: a preliminary investigation.
AB  - BACKGROUND: Approximately 50 to 90% of individuals in North America seeking
      treatment for alcoholism are chronic smokers. A growing body of evidence suggests
      that chronic cigarette smokers show a pattern of neurocognitive dysfunction
      similar to that observed in alcoholic patients. However, previous studies
      investigating neurocognitive recovery in abstinent alcoholic patients did not
      specifically consider the potential effects of chronic cigarette smoking.
      METHODS: This study comprehensively compared longitudinal neurocognitive changes
      over 6 to 9 months of abstinence among 13 nonsmoking recovering alcoholic
      patients (ALC) and 12 actively smoking ALC. The neurocognitive performance of the
      alcoholic groups was compared with nonsmoking light-drinking controls (nonsmoking
      LD). RESULTS: Nonsmoking ALC exhibited a significantly greater magnitude of
      longitudinal improvement than smoking ALC on measures of cognitive efficiency,
      executive skills, visuospatial skills, and working memory. Both nonsmoking ALC
      and smoking ALC demonstrated equivalent improvement on auditory-verbal learning,
      auditory-verbal memory, and processing speed. Nonsmoking LD showed no significant
      changes in neurocognition over time. In cross-sectional comparisons at 6 to 9
      months of abstinence, nonsmoking ALC were superior to smoking ALC on measures of
      auditory-verbal learning, auditory-verbal memory, cognitive efficiency, executive
      skills, processing speed, and working memory. The longitudinal and cross
      sectional neurocognitive differences observed between nonsmoking and smoking ALC
      remained significant after covarying for group differences in education,
      estimated premorbid intelligence alcohol consumption, and other potentially
      confounding variables. In smoking ALC, greater smoking severity was inversely
      related to longitudinal improvement on multiple neurocognitive measures.
      CONCLUSIONS: These preliminary results suggest that chronic smoking may modulate
      neurocognitive recovery in abstinent alcoholic patients. More generally, chronic
      smoking may impact neurocognition in other conditions where is it a prevalent
      behavior.

PMID- 17451400
TI  - College student alcohol consumption, day of the week, and class schedule.
AB  - BACKGROUND: For many college students, Friday class schedules may contribute to
      weekend-like drinking behaviors beginning on Thursday. This study characterizes
      college students' daily alcohol consumption patterns and the relation between
      Thursday drinking and Friday classes overall and for specific vulnerable groups.
      METHODS: A sample of 3,341 volunteer participants was drawn from 3,713 eligible
      first-time undergraduates (56% female, 90% non-Hispanic white). Eligible
      participation rates ranged from 66.5 to 74.0% across follow-ups; 90% contributed
      data at for least one follow-up. Precollege survey and web-based surveys
      administered in the fall and spring semesters across 4 years of college were
      merged with student academic transcripts and university academic schedules at a
      large Midwestern public university. The main outcome measures included past 7-day
      self-reports of drinking behavior for each of 8 semesters. RESULTS: Excessive
      drinking on Thursday, relative to other weekdays, was found and was moderated by
      Friday class schedule: hierarchical linear models indicated that students with no
      Friday classes drank approximately twice as much on Thursdays as students with
      early Friday classes (i.e., mean drinks=1.24 for students with early Friday class
      vs 2.41 for students with no Friday class). Students who had classes beginning at
      12 pm. or later consumed similar amounts as those with no Friday classes
      (M=2.52). The magnitude of the Friday class effect was comparatively larger among
      males and among those who were members of the Greek system or participated in
      Greek activities. Ancillary analyses based on the subset of students who showed
      within-subject variability in Friday classes across semesters (i.e., had both
      early and late or no Friday classes) produced findings similar to those based on
      the entire sample. Little evidence was found for compensatory drinking on Friday
      and Saturday among those with early Friday classes. CONCLUSIONS: Rates and
      amounts of alcohol consumption on Thursday are high, although they appear to be
      influenced by the presence and timing of Friday classes. Friday classes,
      especially those before 10 am, may reduce excessive drinking. Controlled
      institutional interventions are suggested to provide definitive research on the
      causal status of these ostensibly strong effects. This research provides a strong
      rationale for conducting such research.

PMID- 17451401
TI  - Targeted nalmefene with simple medical management in the treatment of heavy
      drinkers: a randomized double-blind placebo-controlled multicenter study.
AB  - BACKGROUND: Clinical studies with opioid antagonists for treatment of problem
      drinking have mainly been conducted in specialized alcohol treatment centers,
      included structured psychosocial treatment, and have focused on maintaining
      abstinence after a period of abstinence from alcohol. METHODS: This multisite,
      randomized double-blind study investigated targeted nalmefene in reducing heavy
      drinking. Specialized alcohol treatment centers and private general practices
      enrolled 403 subjects (328 men, 75 women). Subjects were instructed to take
      nalmefene 10 to 40 mg (n=242) or placebo (n=161) when they believed drinking to
      be imminent. After 28 weeks, 57 subjects from the nalmefene group continued into
      a 24-week randomized withdrawal extension. Concomitant psychosocial intervention
      was minimal and no treatment goals were imposed. Alcohol consumption was recorded
      using the time-line follow-back method. Biochemical indicators of alcohol use
      were also measured. RESULTS: The mean monthly number of heavy drinking days
      (HDDs) during the 12-week period before inclusion was 15.5 (SD 6.9) in the
      nalmefene group and 16.2 (SD 6.9) in the placebo group. During treatment, the
      mean numbers of HDDs were 8.6 to 9.3 in the nalmefene group and 10.6 to 12.0 in
      the placebo group (p=0.0065). The levels of serum alanine aminotransferase and
      gamma-glutamyl transferase decreased in the nalmefene group compared with the
      placebo group (p=0.0088 and 0.0023). During the randomized withdrawal period,
      subjects randomized to placebo apparently returned to heavier drinking. Subjects
      receiving nalmefene reported more nausea, insomnia, fatigue, dizziness, and
      malaise than subjects on placebo. CONCLUSIONS: Nalmefene appears to be effective
      and safe in reducing heavy drinking, even when accompanied by minimal
      psychosocial support.

PMID- 17451402
TI  - Central overexpression of angiotensin AT(1A) receptors prevents dopamine D(2)
      receptor regulation of alcohol consumption in mice.
AB  - BACKGROUND: While angiotensin receptors are found on the soma and terminals of
      dopaminergic neurons, controversy surrounds the potential role of angiotensin in
      alcohol consumption. METHODS: Using a transgenic mouse with a brain-specific
      overexpression of angiotensin AT(1A) receptors (NSE-AT(1A) mice), we have
      examined the role of angiotensin in alcohol consumption and alcohol-induced
      regulation of the dopaminergic system. RESULTS: The functional relevance of the
      overexpressed AT(1A) receptors was confirmed by an exaggerated rehydration
      response following 24-hour dehydration. NSE-AT(1A) mice showed a high preference
      for alcohol (similar to wild-type mice); yet, raclopride treatment had no effect
      on alcohol consumption in NSE-AT(1A) mice, while significantly reducing
      consumption in wild-type mice. In contrast, NSE-AT(1A) mice showed enhanced
      sensitivity to raclopride compared with wild types in terms of D(2) receptor up
      regulation within the ventral mesencephalon. In addition, striatal D(2) receptors
      in NSE-AT(1A) mice were sensitive to up-regulation by chronic alcohol
      consumption. CONCLUSIONS: Collectively, these data imply that while expression of
      angiotensin AT(1A) receptors on striatal neurons has no impact upon basal alcohol
      consumption or preference, AT(1A) receptors do modulate the sensitivity of
      dopamine D(2) receptors to regulation by alcohol and the ability of a D(2)
      receptor antagonist to reduce consumption.

PMID- 17451403
TI  - Identification of candidate genes for alcohol preference by expression profiling
      of congenic rat strains.
AB  - BACKGROUND: A highly significant quantitative trait locus (QTL) on chromosome 4
      that influenced alcohol preference was identified by analyzing crosses between
      the iP and iNP rats. Congenic strains in which the iP chromosome 4 QTL interval
      was transferred to the iNP (NP.P) exhibited the expected increase in alcohol
      consumption compared with the iNP background strain. This study was undertaken to
      identify genes in the chromosome 4 QTL interval that might contribute to the
      differences in alcohol consumption between the alcohol-naive congenic and
      background strains. METHODS: RNA from 5 brain regions from each of 6 NP.P and 6
      iNP rats was labeled and analyzed separately on an Affymetrix Rat Genome 230 2.0
      microarray to look for both cis-regulated and trans-regulated genes. Expression
      levels were normalized using robust multi-chip average (RMA). Differential gene
      expression was validated using quantitative real-time polymerase chain reaction.
      Five individual brain regions (nucleus accumbens, frontal cortex, amygdala,
      hippocampus, and striatum) were analyzed to detect differential expression of
      genes within the introgressed QTL interval, as well as genes outside that region.
      To increase the power to detect differentially expressed genes, combined analyses
      (averaging data from the 5 discrete brain regions of each animal) were also
      carried out. RESULTS: Analyses within individual brain regions that focused on
      genes within the QTL interval detected differential expression in all 5 brain
      regions; a total of 35 genes were detected in at least 1 region, ranging from 6
      genes in the nucleus accumbens to 22 in the frontal cortex. Analysis of the whole
      genome detected very few differentially expressed genes outside the QTL. Combined
      analysis across brain regions was more powerful. Analysis focused on the genes
      within the QTL interval confirmed 19 of the genes detected in individual regions
      and detected 15 additional genes. Whole genome analysis detected 1 differentially
      expressed gene outside the interval. CONCLUSIONS: Cis-regulated candidate genes
      for alcohol consumption were identified using microarray profiling of gene
      expression differences in congenic animals carrying a QTL for alcohol preference.

PMID- 17451404
TI  - Genetic correlation between innate alcohol preference and fear-potentiated
      startle in selected mouse lines.
AB  - BACKGROUND: There is a high rate of co-occurrence between anxiety and alcohol-use
      disorders in humans that may arise from the inheritance of common genes that
      increase the risk for both psychiatric disorders. The purpose of this study was
      to investigate whether a genetic relationship exists between innate alcohol
      preference and propensity to develop learned fear, using the fear-potentiated
      startle (FPS) paradigm, in 2 mouse lines selectively bred for high or low alcohol
      preference. METHODS: Alcohol-naive, male, and female mice from replicate pairs of
      lines selectively bred for high alcohol preference and low alcohol preference
      were randomly assigned to a fear-conditioned or control group. Mice in the fear
      conditioned group received 20 pairings of a light stimulus and footshock; the
      control group received the same number of exposures to light and footshock,
      except that these stimuli were explicitly unpaired. During testing for FPS,
      acoustic stimuli were presented both in the presence and in the absence of the
      light stimulus. RESULTS: In both replicate pairs of lines, mice selectively bred
      for high alcohol preference showed greater FPS than mice selectively bred for low
      alcohol preference. No sex differences in FPS were found in any line. Control
      groups did not show FPS. CONCLUSION: These findings suggest that common genes
      mediate both innate alcohol preference and propensity to develop learned fear in
      these selected mouse lines.

PMID- 17451405
TI  - Mapping of a gene for alopecia with mental retardation syndrome (APMR3) on
      chromosome 18q11.2-q12.2.
AB  - Alopecia with mental retardation syndrome (APMR) is a rare autosomal recessive
      disorder characterized by total or partial absence of hair from the scalp and
      other parts of the body and associated with mental retardation. Previously, we
      have reported the mapping of two alopecia and mental retardation genes (APMR1 and
      APMR2) on human chromosome 3. In the present study, after excluding both of these
      loci through linkage analysis, a whole genome scan was performed by genotyping
      396 polymorphic microsatellite markers located on 22 autosomes and the X and Y
      chromosomes. A disease locus was mapped to a 10.9 cM region, flanked by markers
      D18S866 and D18S811, on chromosome 18q11.2-q12.2. A maximum two-point LOD score
      of 3.03 at theta= 0.0 was obtained with marker D18S1102. Multipoint linkage
      analysis resulted in maximum LOD scores of 4.03 with several markers in the
      candidate region. According to the Rutgers combined linkage-physical map of the
      human genome (build 36) this region covers 12.17 Mb. DNA sequence analysis of
      nine candidate genes including DSC3, DSC1, DSG1, DSG4, DSG3, ZNF397, ZNF271,
      ZNF24 and ZNF396 did not reveal any sequence variants in the affected individuals
      of the family presented here.

PMID- 17451407
TI  - Cardiac tamponade in Hodgkin lymphoma.

PMID- 17451406
TI  - Serum concentrations of angiogenic cytokines in Waldenstrom macroglobulinaemia:
      the ration of angiopoietin-1 to angiopoietin-2 and angiogenin correlate with
      disease severity.
AB  - Angiogenesis represents an essential step of disease progression in several
      haematological malignancies. Microvessel density is increased in 30% of patients
      with Waldenstrom macroglobulinaemia (WM), but there is very limited information
      regarding the role of angiogenic cytokines in this disease. Serum levels of
      vascular endothelial growth factor (VEGF), VEGF-A, angiogenin, angiopoietin (Ang)
      1 and -2, and basic fibroblast growth factor (bFGF) were evaluated in 56 WM
      patients at different disease phases (24 untreated, 20 relapsed/refractory and 12
      patients at remission) and 11 patients with immunoglobulin M type monoclonal
      gammopathy of undetermined significance (IgM-MGUS). All patients had increased
      levels of angiogenin, VEGF, VEGF-A, and bFGF compared with controls. The Ang
      1/Ang-2 ratio was reduced in WM but not in IgM-MGUS patients. Angiogenin levels
      correlated with disease status: when compared with healthy subjects, patients
      with IgM-MGUS and untreated WM patients had increased angiogenin serum levels,
      which were higher in untreated WM patients than in MGUS. WM patients at remission
      had lower angiogenin serum levels compared with untreated patients, but these
      levels were increased again in active disease post-therapy. Angiogenin also
      correlated with albumin levels, while VEGF-A correlated with beta(2)
      microglobulin (beta2M). Ang-1/Ang-2 ratio showed a strong, negative correlation
      with beta2M, and positive correlation with albumin, haemoglobin and
      lymphadenopathy. Our results indicate a potential use of angiogenin levels for
      follow-up in WM and angiogenic molecules as targets for the development of novel
      anti-WM agents.

PMID- 17451408
TI  - Safety and efficacy of bortezomib in high-risk and elderly patients with relapsed
      multiple myeloma.
AB  - Adverse prognostic factors in multiple myeloma include advanced age, number of
      prior therapies, and higher International Staging System (ISS) disease stage. In
      the international, randomised, phase-3 Assessment of Proteasome Inhibition for
      Extending Remissions (APEX) study, bortezomib demonstrated significantly longer
      time to progression (TTP), higher response rates and improved survival compared
      with high-dose dexamethasone in patients with relapsed multiple myeloma following
      one to three prior therapies. In this APEX subgroup analysis, efficacy of
      bortezomib and dexamethasone was compared in elderly (age > or =65 years) and
      high-risk (>1 prior line of therapy; ISS stage II/III; refractory to prior
      therapy) patients. Bortezomib demonstrated substantial clinical activity in these
      patients. Response rate (34-40% vs. 13-19%), including complete response rate (5
      8% vs. 0-1%), was significantly higher with bortezomib versus dexamethasone in
      all four subgroups. Similarly, median TTP was significantly longer with
      bortezomib versus dexamethasone, and 1-year survival probability was
      significantly higher in all subgroups. As in the total APEX population, rates of
      grade 3/4 adverse events were higher in bortezomib- versus dexamethasone-treated
      patients aged > or =65 years and with >1 prior line, while rates of serious
      adverse events were similar; toxicities generally proved manageable. Bortezomib
      should be considered an appropriate treatment for elderly and high-risk patients
      with relapsed multiple myeloma.

PMID- 17451409
TI  - Influence of low-level laser treatment on bone regeneration and osseointegration
      of dental implants following sinus augmentation. An experimental study on sheep.
AB  - OBJECTIVES: The aim of this experimental study was to evaluate if low-level laser
      treatment (LLLT) enhances bone regeneration and osseointegration of dental
      implants in a sinus graft model. MATERIAL AND METHODS: Twelve sheep underwent a
      bilateral sinus floor elevation procedure with cancellous bone from the iliac
      crest. Implant insertion followed 4 weeks (six sheep) and 12 weeks (six sheep)
      later. Sixteen weeks after second-stage surgery, animals were sacrificed.
      Unilaterally, the grafted sinus and during the second-stage surgery the implant
      sites were irradiated intraoperatively and three times during the first
      postoperative week with a diode laser (75 mW, 680 nm). The overall energy density
      per irradiation was 3-4 J/cm(2). Biopsies of the augmented area were obtained
      during implant insertion and after scarification. RESULTS: Bone regeneration
      within the grafted sinus histomorphometric analysis hardly differed between
      control and test side both 4 and 12 weeks after sinus grafting. Osseointegration
      measurements resulted in a significantly higher bone/implant contact (BIC) on the
      test side (P=0.045). Further evaluation of peri-implant bone tends to amount in
      significant higher percentage on the laser side (P=0.053). CONCLUSION: The
      presented experimental study on sheep did not confirm a positive LLLT effect on
      bone regeneration within a cancellous sinus graft. Nevertheless, LLLT possibly
      has a positive effect on osseointegration of dental implants inserted after sinus
      augmentation.

PMID- 17451410
TI  - Lysosome repair enables host cell survival and bacterial persistence following
      Chlamydia trachomatis infection.
AB  - Chlamydiae are obligate intracellular bacteria that replicate within the confines
      of a membrane-bound vacuole termed the inclusion. The final event in the
      infectious process is the disruption of the inclusion membrane and release of a
      multitude of infectious elementary bodies, each capable of eliciting a new
      infection. Strains of the trachoma biovar of Chlamydia trachomatis are released
      from the host cell without concomitant host cell death. In this study, analysis
      of events associated with chlamydial egress revealed that the integrity of the
      host cell plasma membrane was compromised prior to the inclusion membrane. This
      disruption was accompanied by the appearance of LAMP-1 at the infected cell
      surface, implicating lysosome repair of plasma membrane lesions in response to
      infection. Analysis of the effects of calcium chelators and actin stabilizing
      agents, indicated calcium-induced actin depolymerization as a requisite to
      lysosome-plasma membrane fusion and host cell survival. A consequence of this
      lysosome-mediated repair process, was the retention of residual bacteria within
      the surviving host cell, providing a unique mechanism for intracellular
      persistence of C. trachomatis.

PMID- 17451411
TI  - Elicitation and suppression of microbe-associated molecular pattern-triggered
      immunity in plant-microbe interactions.
AB  - Recent studies have uncovered fascinating molecular mechanisms underlying plant
      microbe interactions that coevolved dynamically. As in animals, the primary plant
      innate immunity is immediately triggered by the detection of common pathogen- or
      microbe-associated molecular patterns (PAMPs/MAMPs). Different MAMPs are often
      perceived by distinct cell-surface pattern-recognition receptors (PRRs) and
      activate convergent intracellular signalling pathways in plant cells for broad
      spectrum immunity. Successful pathogens, however, have evolved multiple virulence
      factors to suppress MAMP-triggered immunity. Specifically, diverse pathogenic
      bacteria have employed the type III secretion system to deliver a repertoire of
      virulence effector proteins to interfere with host immunity and promote
      pathogenesis. Plants challenged by pathogens have evolved the secondary plant
      innate immunity. In particular, some plants possess the specific intracellular
      disease resistance (R) proteins to effectively counteract virulence effectors of
      pathogens for effector-triggered immunity. This potent but cultivar-specific
      effector-triggered immunity occurs rapidly with localized programmed cell
      death/hypersensitive response to limit pathogen proliferation and disease
      development. Remarkably, bacteria have further acquired virulence effectors to
      block effector-triggered immunity. This review covers the latest findings in the
      dynamics of MAMP-triggered immunity and its interception by virulence factors of
      pathogenic bacteria.

PMID- 17451412
TI  - Tyrosine phosphorylation controls cortactin binding to two enterohaemorrhagic
      Escherichia coli effectors: Tir and EspFu/TccP.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) is an important food-borne pathogen
      that, upon infection, causes destruction of the microvilli brush border of
      intestinal cells. EHEC is able to recruit several host cell proteins and induce
      actin accumulation beneath its adherence site, forming a pedestal-like structure
      upon which the bacterium is firmly attached. Injection of bacterial effectors
      into the host cells is required to trigger the recruitment and activation of
      proteins, such as cortactin, neural Wiskott-Aldrich syndrome protein (N-WASP) and
      Arp2/3 complex, directly involved in the actin polymerization process. We found
      that cortactin, an actin-binding protein, has a pivotal role during pedestal
      formation by EHEC. Cortactin was found to bind directly to two important
      virulence factors of EHEC, Tir and EspF(u), which are translocated into the host
      cells during infection. Binding of cortactin to these effectors is dependent upon
      tyrosine phosphorylation and a balance between tyrosine phosphorylation and
      dephosphorylation of cortactin is required to regulate pedestal formation by
      EHEC.

PMID- 17451413
TI  - Single-nucleotide polymorphisms in the IL-4 and IL-13 promoter region in
      aggressive periodontitis.
AB  - INTRODUCTION: IL-4 and IL-13 polymorphisms have been shown to influence the
      susceptibility to systemic diseases. In this study, possible associations between
      the IL-4 -590 C-->T, IL-4 -34 C-->T, IL-13 -1112 C-->T and IL-13 -1512 A-->C
      promoter polymorphisms were investigated in subjects with generalized aggressive
      periodontitis (AgP) compared with healthy individuals. MATERIAL AND METHODS:
      Fifty-eight patients with diagnosis of generalized AgP and 51 matched healthy
      controls participated in the study. Blood samples were collected and DNA
      isolated. Molecular analyses were performed by PCR-RFLP in a blind fashion.
      Genotype and allele frequencies among study groups were compared using Fisher's
      exact test (alpha value: 0.05). Pearson's chi(2) test was used for analysis of
      Hardy-Weinberg equilibrium. RESULTS: The frequency of the IL-4 -590 T/T and IL-4 
      34 T/T genotypes differed significantly between groups (p=0.05, 0.02,
      respectively), although the allele frequencies were similar. There was a higher
      frequency of the IL-4 -590 T/T and IL-4 -34 T/T genotypes in patients with AgP
      compared with controls. The genotype and allele frequencies of the IL-13
      polymorphisms did not differ between groups. CONCLUSIONS: This study demonstrated
      an association between the IL-4 -590 T/T and IL-4 -34 T/T genotypes and AgP.
      Further research is necessary to prove if there is an association of these
      polymorphisms with AgP, and if the polymorphisms have a functional effect.

PMID- 17451414
TI  - Relationship between periodontal findings and Behcet's disease: a controlled
      study.
AB  - BACKGROUND: Behcet's disease (BD) is a chronic, relapsing, systemic vasculitis of
      unknown aetiology. The involvement of oral mucosal surfaces represents the onset
      feature of the disease in the majority of patients. OBJECTIVE: The aim of this
      study was to evaluate the periodontal status of BD patients and then compare with
      recurrent aphthous stomatitis (RAS) patients and healthy controls. We also
      determined the relationship between the periodontal condition and the clinical
      severity of the disease in BD patients. METHODS: Eighty-six patients with BD, 63
      patients with RAS and 82 healthy subjects were included in the study. The
      periodontal status of all subjects was evaluated according to the community
      periodontal index of treatment needs (CPITN). BD patients were also assessed for
      clinical severity score (CSS) as described previously. RESULTS: The mean CPITN
      were observed to be higher in BD patients (1.79 +/- 0.96) compared with RAS
      patients (1.22 +/- 0.87) and healthy controls (1.18 +/- 0.98) (p<0.001). There
      was a positive association between CSS and CPITN (p=0.017) in BD patients.
      CONCLUSION: Our results showed that periodondal status is worse in BD patients
      and associated with disease severity. We can speculate that periodontitis may
      induce a systemic inflammatory process that may contribute to the development
      and/or progression of BD.

PMID- 17451415
TI  - Four-year results of a prospective-controlled clinical study evaluating healing
      of intra-bony defects following treatment with an enamel matrix protein
      derivative alone or combined with a bioactive glass.
AB  - AIM: To evaluate the 4-year results following regenerative periodontal surgery at
      intra-bony defects with either a combination of an enamel matrix protein
      derivative (EMD) and a bioactive glass (BG) or with EMD alone. METHODS: Twenty
      five patients with one deep intra-bony defect each were randomly treated with
      either an EMD+BG (test) or with EMD alone (control). Measurements were recorded
      at baseline, at 1 and at 4 years following therapy. The primary outcome variable
      was the clinical attachment level (CAL). RESULTS: The test group demonstrated a
      mean CAL change from 10.3+/-1.6 to 6.7+/-1.2 mm (p<0.001) and to 6.9+/-1.0 mm
      (p<0.001) at 1 and 4 years, respectively. No statistically significant
      differences were found between the 1- and 4-year results. The control group
      showed a mean CAL change from 10.4+/-1.6 to 6.7+/-1.1 mm (p<0.001) at 1 year and
      7.0+/-0.9 mm (p<0.001) at 4 years. The CAL change between 1 and 4 years did not
      present statistically significant differences. In each of the two groups, four
      defects have lost 1 mm of the CAL gained at 1 year. A CAL gain of 1 mm compared
      with the 1-year results was measured in only one defect of the test group.
      Compared with baseline, a CAL gain of >/=3 mm was found at 4 years in 10 defects
      in both groups. Between the treatment groups, no statistically significant
      differences in any of the investigated parameters were observed at 1 and at 4
      years. CONCLUSIONS: Within their limits, the present results indicate that the
      clinical improvements obtained with both regenerative modalities can be
      maintained over a period of 4 years.

PMID- 17451416
TI  - Clinical models that objectively evaluate interproximal plaque based on total
      protein concentration.
AB  - AIM: To establish clinical models that accurately and objectively assess the
      levels of interproximal plaque (IPP) by measuring the total protein
      concentration. MATERIAL AND METHODS: The multiple treatment (MTM) and single
      treatment models (STM) were designed as randomized, double-blinded, crossover
      studies whereby IPP was collected using floss. The total protein concentration in
      the plaque was then measured using a fluorescence microplate assay. To
      demonstrate sensitivity, the levels of residual IPP were compared for two
      distinctly different plaque removal routines: brushing versus brushing+flossing.
      RESULTS: Eighteen subjects completed the study for the MTM, while 16 participants
      completed the study for the STM. The results showed that both models were able to
      distinguish between treatments. Moreover, fundamental profiles were established
      that describe the mean changes in the IPP concentration over time and by
      treatment. Finally, a comparison between our results and a direct measure of IPP,
      i.e., plaque weight, demonstrated the potential of using protein as a
      quantitative means to assess IPP levels. CONCLUSION: The MTM and STM provide an
      objective, quantitative assessment of IPP based on the total protein
      concentration in plaque.

PMID- 17451417
TI  - Gingival crevicular fluid and serum leptin: their relationship to periodontal
      health and disease.
AB  - BACKGROUND & AIMS: Leptin is a pleiotrophic hormone produced by adipose tissue
      and it plays an important role in protection of the host from inflammation and
      infection. The purpose of this study is to determine the presence of leptin in
      gingival crevicular fluid (GCF) and serum samples and to find out their
      association, if any. METHODS: Forty two subjects were selected based on their
      body mass index and were divided into three groups of 14 each; healthy (Group I),
      chronic gingivitis (Group II) and chronic periodontitis (Group III). GCF samples
      (by microcapillary pipettes) and serum samples (by venipuncture) were collected
      to estimate the levels of leptin using enzyme linked immunosorbent assay kit.
      RESULTS: The highest mean leptin concentration in GCF was obtained for Group I
      (2658 pg/ml) and the least for Group III (1312 pg/ml). In contrast, the lowest
      serum leptin concentration was obtained for the Group I (8783 pg/ml), and the
      highest for Group III (12082 pg/ml). This suggests a negative correlation of GCF
      leptin concentration and a positive correlation of serum leptin concentration as
      the clinical attachment level progresses (p<0.05). CONCLUSION: These results
      suggest that greater the periodontal destruction, lesser is the GCF leptin
      concentration and greater the serum leptin concentration.

PMID- 17451418
TI  - Suppression of ES cell differentiation by retinol (vitamin A) via the
      overexpression of Nanog.
AB  - Embryonic stem cells (ESCs) derived from the inner cell mass of blastocysts
      maintain their pluripotency through a complex interplay of different signaling
      pathways and transcription factors including Leukemia Inhibitory Factor (LIF),
      homeo-domain protein Nanog and POU-domain-containing transcription factor Oct3/4.
      LIF can maintain the self-renewal of mouse ESCs by activating the Jak/Stat3
      pathway; however, it is dispensable for human ESCs. Nanog, a homeo-domain
      transcription factor alone is sufficient for sustaining the self-renewal of ESCs.
      Overexpression of Nanog by heterologous promoters can maintain self-renewal of
      human and mouse ESCs in the absence of LIF/Stat3 pathway. The mechanisms that
      control the expression of Nanog, however, remain poorly understood. In this
      report we demonstrate that retinol, the alcohol form of Vitamin A, can suppress
      the differentiation of ESCs by up-regulating the expression of Nanog. Retinol is
      mainly associated with differentiation through its active metabolite retinoic
      acid during early development of the embryo. The activation of Nanog by retinol
      is not mediated via retinoic acid signaling and appears to be independent of
      previously described LIF/Stat3, bone morphogenic proteins, Wnt/beta-catenin, and
      Oct3/4-Sox2 pathways. These studies therefore, reveal a previously unknown
      function of retinol and offer a model system to define alternate regulatory
      pathways that control the self-renewal of ESCs as well as to identify upstream
      "master" regulatory factors that are responsible for maintaining the integrity of
      stem cells.

PMID- 17451419
TI  - Near patient testing for glycated haemoglobin in people with Type 2 diabetes
      mellitus managed in primary care: acceptability and satisfaction.
AB  - AIMS: To assess the acceptability of and satisfaction with near patient testing
      for glycated haemoglobin in primary care in patients and health professionals.
      METHODS: A questionnaire survey and qualitative study were nested within a
      randomized controlled trial conducted in eight general practices in Leicester
      shire, UK. Satisfaction with diabetes care was compared in the intervention group
      (near patient test) and in the control subjects (usual laboratory test), using
      the Diabetes Clinic Satisfaction Questionnaire. Semistructured interviews were
      conducted with a purposive sample of patients and healthcare professionals and
      analysed using thematic coding and framework charting. RESULTS: Questionnaire
      data for 344 patients were analysed and interviews were conducted with 15
      patients and 11 health professionals. Interviews indicated that the near patient
      test was highly acceptable to patients and staff and confirmed that there may be
      potential benefits such as time saving, reduced anxiety and impact on patient
      management and job satisfaction. However, both the survey and the interviews
      identified high pre-existing levels of satisfaction with diabetes care in both
      intervention and control group patients and survey results failed to confirm
      increased patient satisfaction as a result of rapid testing. Limited patient
      understanding of glycated haemoglobin testing was noted. CONCLUSIONS: We were
      unable to confirm actual rather than potential advantages of the near patient
      test. Widespread adoption in primary care cannot be recommended without further
      evidence of benefit.

PMID- 17451420
TI  - Living with Type 2 diabetes: a family perspective.
AB  - AIM: To explore the beliefs, attitudes and perceptions of adults with Type 2
      diabetes and their family members. METHODS: Focus groups were conducted with: (i)
      people with good diabetes control (HbA1c < 7.0%); (ii) their family members;
      (iii) people with poor diabetes control (HbA1c > 8.5%); and (iv) their family
      members. RESULTS: There were no discernible differences between those with good
      and poor diabetes control or between the family members of each group. Overall,
      family members perceived diabetes to be more serious and as having a greater
      impact on daily life than those with the illness. Those with diabetes were
      unaware of this heightened concern and had a more relaxed approach to living with
      diabetes. The lack of information and perceived knowledge about diabetes impacted
      upon participants' causal attributions about the illness and its perceived
      severity. CONCLUSIONS: Diabetes is an illness that affects both individuals and
      families. There is a need for further investigation into the impact that family
      members have on the management of diabetes.

PMID- 17451421
TI  - Effect of raloxifene -- a selective oestrogen receptor modulator -- on kidney
      function in post-menopausal women with Type 2 diabetes: results from a
      randomized, placebo-controlled pilot trial.
AB  - AIMS: Epidemiological and experimental data suggest that activation of the
      oestrogen receptor pathway limits the incidence and the progression of diabetic
      nephropathy. We tested the hypothesis that raloxifene protects against increasing
      urinary albumin excretion in post-menopausal women with Type 2 diabetes in a
      randomized pilot clinical trial. METHODS: We included 39 post-menopausal women
      with Type 2 diabetes and micro- or macro-albuminuria in a 6-month, double-blind,
      placebo-controlled trial: 20 received placebo and 19 received 60 mg raloxifene
      per day. The albumin : creatinine ratio (ACR) in urine was determined on three
      consecutive days during the week before randomization and during the week before
      the final visit. RESULTS: One patient in each group dropped out in the first 3
      weeks, leaving 37 patients for the analysis (19 on placebo and 18 on raloxifene).
      From randomization to the final visit, mean ACR was unchanged in the placebo
      group {277 microg/mg (67; 651) [median (interquartile range)] vs. 284 microg/mg
      (79; 1508)} but decreased slightly in the raloxifene group [376 microg/mg (67;
      615) vs. 243 microg/mg (103; 549)]. This corresponds to a change of +24 (-37;
      +517) for the placebo group vs. -10 microg/mg (-36; +16) for the raloxifene group
      (P = 0.11). In multivariate analysis, raloxifene treatment (P(adjusted) = 0.013),
      baseline low-density lipoprotein (LDL) cholesterol (P(adjusted) = 0.023) and
      change in LDL cholesterol (P(adjusted) = 0.008) were related to the absolute
      change in ACR. Adverse effects were similar in the two groups. CONCLUSIONS: These
      results suggest that raloxifene may limit the progression of albuminuria in post
      menopausal women with diabetes; further studies in a larger population are
      warranted.

PMID- 17451422
TI  - Differential effect of beta-blocker therapy on insulin resistance as a function
      of insulin sensitizer use: results from GEMINI.
AB  - AIMS: To determine whether the beneficial effects of carvedilol on insulin
      resistance (IR) are affected by the concomitant use of insulin sensitizers
      [thiazolidinediones (TZDs) and metformin]. METHODS: Changes in HbA1c and
      homeostasis model assessment-insulin resistance (HOMA-IR) were assessed over 5
      months, comparing carvedilol with metoprolol tartrate according to insulin
      sensitizer (TZDs and metformin) use. RESULTS: In TZD/metformin users, carvedilol
      patients showed a 5.4% decrease [95% confidence interval (CI) -11.9, 1.6; P =
      0.13] and metoprolol tartrate patients showed a 2.8% decrease (95% CI -8.5, 3.2;
      P = 0.35) in HOMA-IR. The -2.6% difference between treatments was not significant
      (95% CI -10.7, 6.2; P = 0.55). In contrast, those not taking TZD/metformin
      experienced a 13.2% increase in HOMA-IR on metoprolol tartrate (95% CI 3.2, 24.1;
      P < 0.01) and a 4.8% decrease in HOMA-IR on carvedilol (95% CI -14.6, 6.0; P =
      0.37), with a significant treatment difference of -15.9% favouring carvedilol
      (95% CI -26.6, -3.6; P = 0.01). There was no significant treatment interaction
      for the use of TZD/metformin and HbA1c. A statistically significant treatment
      difference was observed for HbA1c after 5 months favouring carvedilol after
      adjusting for insulin sensitizer use (-0.11%, 95% CI -0.214, -0.009; P = 0.03).
      CONCLUSIONS: In patients with diabetes and hypertension not taking insulin
      sensitizers, the use of metoprolol tartrate resulted in a worsening of insulin
      resistance, an effect not seen with carvedilol. However, in TZD/metformin users
      the difference between the beta-blockers was not statistically significant.

PMID- 17451423
TI  - A prospective randomized controlled trial of lifestyle intervention on quality of
      life and cardiovascular risk score in patients with obesity and type 2 diabetes.

PMID- 17451424
TI  - Sudden cardiac death: influence of diabetes.
AB  - This article reviews current thinking on the problem of sudden cardiac death
      (SCD) within community settings, highlighting progress in understanding risks and
      mechanisms. Information available on the influence of diabetes as a risk factor
      for SCD and the question of whether this disease enhances susceptibility to
      ventricular arrhythmias is summarized as are central strategies in risk
      stratification and mortality prevention.

PMID- 17451426
TI  - Beta cells in type 2 diabetes - a crucial contribution to pathogenesis.
AB  - The healthy beta-cell has an enormous capacity to adapt to conditions of higher
      insulin demand (e.g. in obesity, pregnancy, cortisol excess) to maintain
      normoglycaemia with an increase in its functional beta-cell mass. This
      compensates in 80-90% of individuals for insulin resistance. However, in 10-20%
      of individuals, the beta-cells are unable to match the demands of insulin
      resistance and insulin levels are relatively insufficient to maintain normal
      glycaemic control. This eventually leads to glucose intolerance and type 2
      diabetes (T2DM). Accordingly, preservation of functional beta-cell mass has
      become central in the treatment of type 1 diabetes as well as T2DM. The purpose
      of this review is to summarize the recently described mechanisms of beta-cell
      death in T2DM and to postulate possible new targets for treatment.

PMID- 17451425
TI  - Efficacy of ezetimibe/simvastatin 10/20 and 10/40 mg compared with atorvastatin
      20 mg in patients with type 2 diabetes mellitus.
AB  - AIM: This randomized, double-blind study evaluated the efficacy of switching from
      atorvastatin (ATV) 10 mg to ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg, EZE/SIMVA
      10/40 mg or doubling the dose of ATV from 10 to 20 mg in patients with type 2
      diabetes (T2D). METHODS: Eligible patients had haemoglobin A(1C)< or =10%, were
      aged > or =18 years and were on ATV 10 mg for > or =6 weeks before study entry.
      After a 4-week open-label ATV 10 mg run-in, patients were randomized to EZE/SIMVA
      10/20 mg (n = 220), EZE/SIMVA 10/40 mg (n = 222) or ATV 20 g (n = 219) daily for
      6 weeks. RESULTS: Greater (p < or = 0.001) reductions in low-density lipoprotein
      cholesterol (LDL-C) (the primary end-point) were achieved by switching to
      EZE/SIMVA 10/20 mg (26.2%) or 10/40 mg (30.1%) than by doubling the dose of ATV
      to 20 mg (8.5%). EZE/SIMVA 10/20 mg and 10/40 mg produced greater (p < or =
      0.001) reductions in total cholesterol, non-high-density lipoprotein cholesterol
      (HDL-C) and apolipoprotein B relative to ATV 20 mg. A reduction (p < or = 0.050)
      in C-reactive protein was observed with EZE/SIMVA 10/40 mg vs. ATV 20 mg. Similar
      reductions in triglycerides were observed across the three groups, and none of
      the treatments produced a significant change in HDL-C. A greater (p < or = 0.001)
      proportion of patients achieved LDL-C <2.5 mmol/l with EZE/SIMVA 10/20 mg (90.5%)
      and 10/40 mg (87.0%) than with ATV 20 mg (70.4%). Both EZE/SIMVA doses were
      generally well tolerated, with an overall safety profile similar to ATV 20 mg.
      CONCLUSIONS: EZE/SIMVA 10/20 and 10/40 mg provided greater lipid-altering
      efficacy than doubling the dose of ATV from 10 to 20 mg and were well tolerated
      in patients with T2D.

PMID- 17451427
TI  - Cardiovascular disease risk assessment in patients with obstructive sleep apnoea:
      clinical utility of the Framingham risk equation for initiating statins.

PMID- 17451428
TI  - Peroxin Pex21p interacts with the C-terminal noncatalytic domain of yeast seryl
      tRNA synthetase and forms a specific ternary complex with tRNA(Ser).
AB  - The seryl-tRNA synthetase from Saccharomyces cerevisiae interacts with the
      peroxisome biogenesis-related factor Pex21p. Several deletion mutants of seryl
      tRNA synthetase were constructed and inspected for their ability to interact with
      Pex21p in a yeast two-hybrid assay, allowing mapping of the synthetase domain
      required for complex assembly. Deletion of the 13 C-terminal amino acids
      abolished Pex21p binding to seryl-tRNA synthetase. The catalytic parameters of
      purified truncated seryl-tRNA synthetase, determined in the serylation reaction,
      were found to be almost identical to those of the native enzyme. In vivo loss of
      interaction with Pex21p was confirmed in vitro by coaffinity purification. These
      data indicate that the C-terminally appended domain of yeast seryl-tRNA
      synthetase does not participate in substrate binding, but instead is required for
      association with Pex21p. We further determined that Pex21p does not directly bind
      tRNA, and nor does it possess a tRNA-binding motif, but it instead participates
      in the formation of a specific ternary complex with seryl-tRNA synthetase and
      tRNA(Ser), strengthening the interaction of seryl-tRNA synthetase with its
      cognate tRNA(Ser).

PMID- 17451429
TI  - Lithium increases PGC-1alpha expression and mitochondrial biogenesis in primary
      bovine aortic endothelial cells.
AB  - Lithium is a therapeutic agent commonly used to treat bipolar disorder and its
      beneficial effects are thought to be due to a combination of activation of the
      Wnt/beta-catenin pathway via inhibition of glycogen synthase kinase-3beta and
      depletion of the inositol pool via inhibition of the inositol monophosphatase-1.
      We demonstrated that lithium in primary endothelial cells induced an increase in
      mitochondrial mass leading to an increase in ATP production without any
      significant change in mitochondrial efficiency. This increase in mitochondrial
      mass was associated with an increase in the mRNA levels of mitochondrial
      biogenesis transcription factors: nuclear respiratory factor-1 and -2beta, as
      well as mitochondrial transcription factors A and B2, which lead to the
      coordinated upregulation of oxidative phosphorylation components encoded by
      either the nuclear or mitochondrial genome. These effects of lithium on
      mitochondrial biogenesis were independent of the inhibition of glycogen synthase
      kinase-3beta and independent of inositol depletion. Also, expression of the
      coactivator PGC-1alpha was increased, whereas expression of the coactivator PRC
      was not affected. Lithium treatment rapidly induced a decrease in activating Akt
      Ser473 phosphorylation and inhibitory Forkhead box class O (FOXO1)-Thr24
      phosphorylation, as well as an increase in activating c-AMP responsive element
      binding (CREB)-Ser133 phosphorylation, two mechanisms known to control PGC-1alpha
      expression. Together, our results show that lithium induces mitochondrial
      biogenesis via CREB/PGC-1alpha and FOXO1/PGC-1alpha cascades, which highlight the
      pleiotropic effects of lithium and reveal also novel beneficial effects via
      preservation of mitochondrial functions.

PMID- 17451430
TI  - Metabolic pathway that produces essential fatty acids from polymethylene
      interrupted polyunsaturated fatty acids in animal cells.
AB  - Sciadonic acid (20:3 Delta-5,11,14) and juniperonic acid (20:4 Delta-5,11,14,17)
      are polyunsaturated fatty acids (PUFAs) that lack the Delta-8 double bond of
      arachidonic acid (20:4 Delta-5,8,11,14) and eicosapentaenoic acid (20:5 Delta
      5,8,11,14,17), respectively. Here, we demonstrate that these conifer oil-derived
      PUFAs are metabolized to essential fatty acids in animal cells. When Swiss 3T3
      cells were cultured with sciadonic acid, linoleic acid (18:2 Delta-9,12)
      accumulated in the cells to an extent dependent on the concentration of sciadonic
      acid. At the same time, a small amount of 16:2 Delta-7,10 appeared in the
      cellular lipids. Both 16:2 Delta-7,10 and linoleic acid accumulated in sciadonic
      acid-supplemented CHO cells, but not in peroxisome-deficient CHO cells. We
      confirmed that 16:2 Delta-7,10 was effectively elongated to linoleic acid in rat
      liver microsomes. These results indicate that sciadonic acid was partially
      degraded to 16:2 Delta-7,10 by two cycles of beta-oxidation in peroxisomes, then
      elongated to linoleic acid in microsomes. Supplementation of Swiss 3T3 cells with
      juniperonic acid, an n-3 analogue of sciadonic acid, induced accumulation of
      alpha-linolenic acid (18:3 Delta-9,12,15) in cellular lipids, suggesting that
      juniperonic acid was metabolized in a similar manner to sciadonic acid. This PUFA
      remodeling is thought to be a process that converts unsuitable fatty acids into
      essential fatty acids required by animals.

PMID- 17451431
TI  - Membrane trafficking of CD98 and its ligand galectin 3 in BeWo cells--implication
      for placental cell fusion.
AB  - CD98 heavy chain (CD98hc), expressed at high levels in developing human
      trophoblasts, is an integral membrane protein with multiple N-linked
      glycosylation sites and known to be important for cell fusion, adhesion, and
      amino acid transport. Western blotting and flow cytometry were used to study the
      effect of brefeldin A, an inhibitor of protein translocation through the Golgi,
      on CD98hc in the human placental trophoblast cell line BeWo. Although brefeldin A
      treatment caused increased cell surface expression of CD98hc, a novel partially
      glycosylated form of the protein was found and, concomitantly, cell fusion was
      reduced. Western blotting showed that CD98 and galectin 3, a proposed ligand for
      the glycosylated extracellular domain of CD98hc, co-immunoprecipitated, and
      double-label immuno-electron microscopy confirmed that CD98hc associated with
      galectin 3. Furthermore, cell fusion was reduced (specifically) by the
      disaccharide lactose, a known ligand for the carbohydrate recognition domain of
      galectin 3, suggesting that the association was functional. Taken together, the
      data suggest that N-glycosylation of CD98 and subsequent interaction with
      galectin 3 is critical for aspects of placental cell biology, and provides a
      rationale for the observation that, in the mouse, truncation of the CD98hc
      extracellular domain leads to early embryonic lethality [Tsumura H, Suzuki N,
      Saito H, Kawano M, Otake S, Kozuka Y, Komada H, Tsurudome M & Ito Y (2003)
      Biochem Biophys Res Commun 308, 847-851].

PMID- 17451432
TI  - Involvement of NF-kappaB subunit p65 and retinoic acid receptors, RARalpha and
      RXRalpha, in transcriptional regulation of the human GnRH II gene.
AB  - Gonadotropin-releasing hormone (GnRH) I and II are hypothalamic decapeptides with
      pivotal roles in the development of reproductive competence and regulation of
      reproductive events. In this study, transcriptional regulation of the human GnRH
      II gene was investigated. By scanning mutation analysis coupled with transient
      promoter assays, the motif at -641/-636 (CATGCC, designated GII-Sil) was
      identified as a repressor element. Mutation of this motif led to full restoration
      of promoter activity in TE671 medulloblastoma and JEG-3 placenta choriocarcinoma
      cells. Supershift and chromatin immunoprecipitation assays showed in vitro and in
      vivo binding of NF-kappaB subunit p65 and the retinoic acid receptors, RARalpha
      and RXRalpha, to the promoter sequences. Over-expression of these protein factors
      indicated that p65 is a potent repressor, and the RARalpha/RXRalpha heterodimer
      is involved in the differential regulation of the GnRH II gene in neuronal and
      placental cells. This was confirmed by quantitative real-time PCR. Treatment of
      cells with the RARalpha/RXRalpha ligands, all-trans retinoic acid and 9-cis
      retinoic acid, reduced and increased GnRH II gene expression in TE671 and JEG-3
      cells, respectively. Taken together, these data demonstrate the differential
      roles of NF-kappaB p65 and RARalpha/RXRalpha, interacting with the same sequence
      in the promoter of the human GnRH II gene to influence gene expression in a cell
      specific manner.

PMID- 17451433
TI  - A robust metallo-oxidase from the hyperthermophilic bacterium Aquifex aeolicus.
AB  - The gene, Aquifex aeolicus AAC07157.1, encoding a multicopper oxidase (McoA) and
      localized in the genome as part of a putative copper-resistance determinant, has
      been cloned, over-expressed in Escherichia coli and the recombinant enzyme
      purified to homogeneity. The purified enzyme shows spectroscopic and biochemical
      characteristics typical of the well-characterized multicopper oxidase family of
      enzymes. McoA presents higher specificity (k(cat)/K(m)) for cuprous and ferrous
      ions than for aromatic substrates and is therefore designated as a metallo
      oxidase. Addition of copper is required for maximal catalytic efficiency. A
      comparative model structure of McoA has been constructed and a striking
      structural feature is the presence of a methionine-rich region (residues 321
      363), reminiscent of those found in copper homeostasis proteins. The kinetic
      properties of a mutant enzyme, McoADeltaP321-V363, deleted in the methionine-rich
      region, provide evidence for the key role of this region in the modulation of the
      catalytic mechanism. McoA has an optimal temperature of 75 degrees C and presents
      remarkable heat stability at 80 and 90 degrees C, with activity lasting for up to
      9 and 5 h, respectively. McoA probably contributes to copper and iron homeostasis
      in A. aeolicus.

PMID- 17451434
TI  - The crystal structure of the ring-hydroxylating dioxygenase from Sphingomonas CHY
      1.
AB  - The ring-hydroxylating dioxygenase (RHD) from Sphingomonas CHY-1 is remarkable
      due to its ability to initiate the oxidation of a wide range of polycyclic
      aromatic hydrocarbons (PAHs), including PAHs containing four- and five-fused
      rings, known pollutants for their toxic nature. Although the terminal oxygenase
      from CHY-1 exhibits limited sequence similarity with well characterized RHDs from
      the naphthalene dioxygenase family, the crystal structure determined to 1.85 A by
      molecular replacement revealed the enzyme to share the same global
      alpha(3)beta(3) structural pattern. The catalytic domain distinguishes itself
      from other bacterial non-heme Rieske iron oxygenases by a substantially larger
      hydrophobic substrate binding pocket, the largest ever reported for this type of
      enzyme. While residues in the proximal region close to the mononuclear iron atom
      are conserved, the central region of the catalytic pocket is shaped mainly by the
      side chains of three amino acids, Phe350, Phe404 and Leu356, which contribute to
      the rather uniform trapezoidal shape of the pocket. Two flexible loops, LI and
      LII, exposed to the solvent seem to control the substrate access to the catalytic
      pocket and control the pocket length. Compared with other naphthalene
      dioxygenases residues Leu223 and Leu226, on loop LI, are moved towards the
      solvent, thus elongating the catalytic pocket by at least 2 A. An 11 A long water
      channel extends from the interface between the alpha and beta subunits to the
      catalytic site. The comparison of these structures with other known oxygenases
      suggests that the broad substrate specificity presented by the CHY-1 oxygenase is
      primarily due to the large size and particular topology of its catalytic pocket
      and provided the basis for the study of its reaction mechanism.

PMID- 17451435
TI  - Globin gene family evolution and functional diversification in annelids.
AB  - Globins are the most common type of oxygen-binding protein in annelids. In this
      paper, we show that circulating intracellular globin (Alvinella pompejana and
      Glycera dibranchiata), noncirculating intracellular globin (Arenicola marina
      myoglobin) and extracellular globin from various annelids share a similar gene
      structure, with two conserved introns at canonical positions B12.2 and G7.0.
      Despite sequence divergence between intracellular and extracellular globins,
      these data strongly suggest that these three globin types are derived from a
      common ancestral globin-like gene and evolved by duplication events leading to
      diversification of globin types and derived functions. A phylogenetic analysis
      shows a distinct evolutionary history of annelid extracellular hemoglobins with
      respect to intracellular annelid hemoglobins and mollusc and arthropod
      extracellular hemoglobins. In addition, dehaloperoxidase (DHP) from the annelid,
      Amphitrite ornata, surprisingly exhibits close phylogenetic relationships to some
      annelid intracellular globins. We have characterized the gene structure of A.
      ornata DHP to confirm assumptions about its homology with globins. It appears
      that it has the same intron position as in globin genes, suggesting a common
      ancestry with globins. In A. ornata, DHP may be a derived globin with an unusual
      enzymatic function.

PMID- 17451436
TI  - Insights into the structure of plant alpha-type phospholipase D.
AB  - Phospholipases D play an important role in the regulation of cellular processes
      in plants and mammals. Moreover, they are an essential tool in the synthesis of
      phospholipids and phospholipid analogs. Knowledge of phospholipase D structures,
      however, is widely restricted to sequence data. The only known tertiary structure
      of a microbial phospholipase D cannot be generalized to eukaryotic phospholipases
      D. In this study, the isoenzyme form of phospholipase D from white cabbage
      (PLDalpha2), which is the most widely used plant phospholipase D in biocatalytic
      applications, has been characterized by small-angle X-ray scattering, UV
      absorption, CD and fluorescence spectroscopy to yield the first insights into its
      secondary and tertiary structure. The structural model derived from small-angle X
      ray scattering measurements reveals a barrel-shaped monomer with loosely
      structured tops. The far-UV CD-spectroscopic data indicate the presence of alpha
      helical as well as beta-structural elements, with the latter being dominant. The
      fluorescence and near-UV CD spectra point to tight packing of the aromatic
      residues in the core of the protein. From the near-UV CD signals and activity
      data as a function of the calcium ion concentration, two binding events
      characterized by dissociation constants in the ranges of 0.1 mm and 10-20 mm can
      be confirmed. The stability of PLDalpha2 proved to be substantially reduced in
      the presence of calcium ions, with salt-induced aggregation being the main reason
      for irreversible inactivation.

PMID- 17451437
TI  - Role of receptor-mediated endocytosis, endosomal acidification and cathepsin D in
      cholera toxin cytotoxicity.
AB  - Using the in situ liver model system, we have recently shown that, after cholera
      toxin binding to hepatic cells, cholera toxin accumulates in a low-density
      endosomal compartment, and then undergoes endosomal proteolysis by the aspartic
      acid protease cathepsin-D [Merlen C, Fayol-Messaoudi D, Fabrega S, El Hage T,
      Servin A, Authier F (2005) FEBS J272, 4385-4397]. Here, we have used a
      subcellular fractionation approach to address the in vivo compartmentalization
      and cytotoxic action of cholera toxin in rat liver parenchyma. Following
      administration of a saturating dose of cholera toxin to rats, rapid endocytosis
      of both cholera toxin subunits was observed, coincident with massive
      internalization of both the 45 kDa and 47 kDa Gsalpha proteins. These events
      coincided with the endosomal recruitment of ADP-ribosylation factor proteins,
      especially ADP-ribosylation factor-6, with a time course identical to that of
      toxin and the A subunit of the stimulatory G protein (Gsalpha) translocation.
      After an initial lag phase of 30 min, these constituents were linked to NAD
      dependent ADP-ribosylation of endogenous Gsalpha, with maximum accumulation
      observed at 30-60 min postinjection. Assessment of the subsequent postendosomal
      fate of internalized Gsalpha revealed sustained endolysosomal transfer of the two
      Gsalpha isoforms. Concomitantly, cholera toxin increased in vivo endosome
      acidification rates driven by the ATP-dependent H(+)-ATPase pump and in vitro
      vacuolar acidification in hepatoma HepG2 cells. The vacuolar H(+)-ATPase
      inhibitor bafilomycin and the cathepsin D inhibitor pepstatin A partially
      inhibited, both in vivo and in vitro, the cAMP response to cholera toxin. This
      cathepsin D-dependent action of cholera toxin under the control of endosomal
      acidity was confirmed using cellular systems in which modification of the
      expression levels of cathepsin D, either by transfection of the cathepsin D gene
      or small interfering RNA, was followed by parallel changes in the cytotoxic
      response to cholera toxin. Thus, in hepatic cells, a unique endocytic pathway was
      revealed following cholera toxin administration, with regulation specificity most
      probably occurring at the locus of the endosome and implicating endosomal
      proteases, such as cathepsin D, as well as organelle acidification.

PMID- 17451438
TI  - From functional genomics to systems biology.
AB  - This review discusses the talks presented at the third EMBL Biennial Symposium,
      From functional genomics to systems biology, held in Heidelberg, Germany, 14-17
      October 2006. Current issues and trends in various subfields of functional
      genomics and systems biology are considered, including analysis of regulatory
      elements, signalling networks, transcription networks, protein-protein
      interaction networks, genetic interaction networks, medical applications of DNA
      microarrays, and metagenomics. Several technological advances in the fields of
      DNA microarrays, identification of regulatory elements in the genomes of higher
      eukaryotes, and MS for detection of protein interactions are introduced. Major
      directions of future systems biology research are also discussed.

PMID- 17451440
TI  - Directed evolution of trimethoprim resistance in Escherichia coli.
AB  - Directed evolution is a useful tool in the study of enzymes. It is used in this
      study to investigate the means by which resistance to the antibiotic trimethoprim
      develops in dihyrofolate reductase from Escherichia coli. Mutants with clinical
      levels of resistance were obtained after only three generations. After four
      generations of directed evolution, several mutants were characterized, along with
      some point mutants made to investigate amino acid changes of interest. Several
      mutations were found to grant resistance to trimethoprim, both by reducing the
      binding affinity of the enzyme for the drug, and by increasing the activity of
      the enzyme.

PMID- 17451439
TI  - Enzymes that hydrolyze adenine nucleotides of patients with hypercholesterolemia
      and inflammatory processes.
AB  - The activity of NTPDase (EC 3.6.1.5, apyrase, CD39) was verified in platelets
      from patients with increasing cholesterol levels. A possible association between
      cholesterol levels and inflammatory markers, such as oxidized low-density
      lipoprotein, highly sensitive C-reactive protein and oxidized low-density
      lipoprotein autoantibodies, was also investigated. Lipid peroxidation was
      estimated by measurement of thiobarbituric acid reactive substances in serum. The
      following groups were studied: group I, < 150 mg.dL(-1) cholesterol; group II,
      151-200 mg.dL(-1) cholesterol; group III, 201-250 mg.dL(-1) cholesterol; and
      group IV, > 251 mg.dL(-1) cholesterol. The results demonstrated that both ATP
      hydrolysis and ADP hydrolysis were enhanced as a function of cholesterol level.
      Low-density lipoprotein levels increased concomitantly with total cholesterol
      levels. Triglyceride levels were increased in the groups with total cholesterol
      above 251 mg.dL(-1). Oxidized low-density lipoprotein levels were elevated in
      groups II, III, and IV. Highly sensitive C-reactive protein was elevated in the
      group with cholesterol levels higher than 251 mg.dL(-1). Oxidized low-density
      lipoprotein autoantibodies were elevated in groups III and IV. Thiobarbituric
      acid reactive substance content was enhanced as a function of cholesterol level.
      In summary, hypercholesterolemia is associated with enhancement of inflammatory
      response, oxidative stress, and ATP and ADP hydrolysis. The increased ATP and ADP
      hydrolysis in group IV was confirmed by an increase in CD39 expression on its
      surface. The increase in CD39 activity is possibly related to a compensatory
      response to the inflammatory and pro-oxidative state associated with
      hypercholesterolemia.

PMID- 17451441
TI  - Prediction of rotational orientation of transmembrane helical segments of
      integral membrane proteins using new environment-based propensities for amino
      acids derived from structural analyses.
AB  - Alpha-helical integral-membrane proteins (IMPs) play a key role in many
      biological processes, such as signal transduction, and are targets for >50% of
      current therapeutic drugs. In contrast to their significant abundance and
      biological importance, they comprise <1% of structurally solved proteins. In the
      absence of experimental evidence, molecular modeling of IMP structures is an
      alternative for providing structural information and aiding further experimental
      design. In the current work, we propose two new amino acid lipid-facing
      propensity scales derived from the structural analysis of a nonredundant set of
      water-soluble proteins. The new scales, pi and delta, perform as well or better
      than published scales (Carugo's hydrophobicity and kPROT scales) in predicting
      the lipid-facing side of helical segments of a set of structurally solved IMPs,
      thus indicating (a) that the folding properties of water-soluble proteins and
      IMPs are similar, and (b) that the new scales will prove useful in modeling the
      transmembrane segments of IMPs.

PMID- 17451442
TI  - An oral Salmonella vaccine promotes the down-regulation of cell surface Toll-like
      receptor 4 (TLR4) and TLR2 expression in mice.
AB  - A single oral immunization with the Lon-protease-deficient Salmonella enterica
      serovar Typhimurium (strain CS2022) induced protective immunity in mice against a
      subcutaneous challenge with virulent Listeria monocytogenes as well as virulent
      Salmonella serovar Typhimurium. The populations of cell surface Toll-like
      receptor 4 (TLR4) and TLR2 on peritoneal macrophages decreased at week 6 after
      immunization. This population decrease was not reversed after a challenge with
      either Salmonella or Listeria. These results suggest that oral immunization with
      CS2022 induced immune tolerance correlated with the down-regulation of cell
      surface TLR expression. This down-regulation may in part account for the
      development of cross-protection against a Listeria challenge by immunization with
      CS2022.

PMID- 17451443
TI  - Phagocytosis of Fonsecaea pedrosoi conidia, but not sclerotic cells caused by
      Langerhans cells, inhibits CD40 and B7-2 expression.
AB  - Fonsecaea pedrosoi is the major etiological agent of chromoblastomycosis, a
      chronic, suppurative, granulomatous mycosis usually confined to skin and
      subcutaneous tissues, presenting a worldwide distribution. The host defense
      mechanisms in chromoblastomycosis have not been extensively investigated.
      Langerhans cells (LC) are bone-marrow-derived, dendritic antigen-presenting cells
      of the epidermis, which constitutively express major histocompatibility complex
      (MHC) class II, and comprise 1-3% of total epidermal cells. LC are localized in
      suprabasal layers of the epidermis and in mucosa, where they play important roles
      in skin immune responses. The purpose of the present study was to evaluate the
      interaction of F. pedrosoi conidia or sclerotic cells with LC purified from
      BALB/c mice skin. We demonstrate here that LC phagocytose F. pedrosoi conidia but
      not sclerotic cells in the first 3 h of interaction, inhibiting hyphae formation
      during 12-hour coculture from both forms, internalized or not. Also, LC
      maturation, analyzed using CD40 and B7-2 expression, was inhibited by conidia,
      but not by sclerotic cells, indicating an important innate immunity function of
      LC against F. pedrosoi infection in these mice.

PMID- 17451444
TI  - Isolation and characterization of Bacillus thioparus sp. nov.,
      chemolithoautotrophic, thiosulfate-oxidizing bacterium.
AB  - A novel bacterium, strain BMP-1(T), was isolated from a continuous wastewater
      treatment culture system operating with a bacterial consortium. Cells of the
      isolate were Gram-variable, aerobic, moderately halotolerant, motile and
      endospore-forming rods. Strain BMP-1(T) grew chemolithoautotrophically by
      oxidation of thiosulfate to sulfate with a growth yield of 1.07 g protein mol(-1)
      of thiosulfate consumed. DNA G+C content was 43.8 mol%. Its cell wall had
      peptidoglycan based on m-diaminopimelic acid, and the major component of fatty
      acid was C(15 : 0). The 16S rRNA gene analysis showed that strain belongs to the
      genus Bacillus, sharing a 99.5% of sequence similarity with Bacillus jeotgali CCM
      7133(T). DNA-DNA hybridization between the isolate of this study and this strain
      was 44%. Thus, the inclusion of strain BMP-1(T) in the genus Bacillus is
      suggested as a novel species and the name Bacillus thioparus sp. nov. (Type
      strain BMP-1(T)=BM-B-436(T)=CECT 7196(T)) is proposed. The sequence of the 16S
      rRNA gene has been deposited in GenBank with accession number DQ371431.

PMID- 17451445
TI  - Mesorhizobium spp. are the main microsymbionts of Caragana spp. grown in Liaoning
      Province of China.
AB  - Caragana species are woody legumes widely distributed in the arid regions of
      China. These plants form root nodules but their nodule bacteria have not been
      clearly classified. A total of 112 symbiotic bacterial isolates were obtained
      from four Caragana species grown in Liaoning Province and were characterized with
      ARDRA, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins, BOX
      PCR and sequencing of the 16S rRNA gene. Most of them were classified as
      Mesorhizobium belonging to 11 putative species. Three isolates were identified as
      Rhizobium etli and Burkholderia spp. This study offers new information about the
      Caragana-rhizobia association and resource for selection of inoculants used in
      sustainable agriculture and for further studies on the Caragana rhizobia.

PMID- 17451446
TI  - EspP, a Type V-secreted serine protease of enterohaemorrhagic Escherichia coli
      O157:H7, influences intestinal colonization of calves and adherence to bovine
      primary intestinal epithelial cells.
AB  - Enterohaemorrhagic Escherichia coli (EHEC) comprise a group of zoonotic
      diarrhoeal pathogens of worldwide importance. Cattle are a key reservoir; however
      the molecular mechanisms that promote persistent colonization of the bovine
      intestines by EHEC are ill-defined. The large plasmid of EHEC O157:H7 encodes
      several putative virulence factors. Here, it is reported that the pO157-encoded
      Type V-secreted serine protease EspP influences the intestinal colonization of
      calves. To dissect the basis of attenuation, a bovine primary rectal epithelial
      cell line was developed. Adherence of E. coli O157:H7 to such cells was
      significantly impaired by espP mutation but restored upon addition of highly
      purified exogenous EspP. Data of this study add to the growing body of evidence
      that cytotoxins facilitate intestinal colonization by EHEC.

PMID- 17451447
TI  - Antifungal activity of lactobacilli isolated from salami.
AB  - Sixty-five strains of lactobacilli isolated from salami were tested for their
      antifungal activity in early and late phases of growth. Ten strains showed
      inhibitory activity in the early phase of growth towards moulds such as
      Aspergillus and Penicillium. The active compounds identified were phenyl-lactate
      and hydroxy-phenyl-lactate. All strains tested had activity in the late phase,
      after autolysis. The compounds released were peptidic and showed antifungal
      activity.

PMID- 17451448
TI  - Porphyromonas gingivalis short fimbriae are regulated by a FimS/FimR two
      component system.
AB  - Porphyromonas gingivalis possesses two distinct fimbriae. The long (FimA)
      fimbriae have been extensively studied. Expression of the fimA gene is tightly
      controlled by a two-component system (FimS/FimR) through a cascade regulation.
      The short (Mfa1) fimbriae are less understood. The authors have recently
      demonstrated that both fimbriae are required for formation of P. gingivalis
      biofilms. Here, the novel finding that FimR, a member of the two-component
      regulatory system, is a transcriptional activator of the mfa1 gene is promoted.
      Unlike the regulatory mechanism of FimA by FimR, this regulation of the mfa1 gene
      is accomplished by FimR directly binding to the promoter region of mfa1.

PMID- 17451449
TI  - Analysis of S-adenosylmethionine binding to Afsk, a protein kinase from
      Streptomyces coelicolor.

PMID- 17451450
TI  - Cdc37p is involved in osmoadaptation and controls high osmolarity-induced cross
      talk via the MAP kinase Kss1p.
AB  - Cdc37p, the p50 homolog of Saccharomyces cerevisiae, is an Hsp90 cochaperone
      involved in the targeting of protein kinases to Hsp90. Here we report a role for
      Cdc37p in osmoadaptive signalling in this yeast. The osmosensitive phenotype that
      is displayed by the cdc37-34 mutant strain appears not to be the consequence of
      deficient signalling through the high osmolarity glycerol (HOG) MAP kinase
      pathway. Rather, Cdc37p appears to play a role in the filamentous growth (FG)
      pathway, which mediates adaptation to high osmolarity parallel to the HOG
      pathway. The osmosensitive phenotype of the cdc37-34 mutant strain is aggravated
      upon the deletion of the HOG gene. We report that the hyper-osmosensitive
      phenotype of the cdc37-34, hog1 mutant correlates to a reduced of activity of the
      FG pathway. We utilized this phenotype to isolate suppressor genes such as KSS1
      that encodes a MAP kinase that functions in the FG pathway. We report that Kss1p
      interacts physically with Cdc37p. Like Kss1p, the second suppressor that we
      isolated, Dse1p, is involved in cell wall biogenesis or maintenance, suggesting
      that Cdc37p controls osmoadapation by regulating mitogen-activated protein kinase
      signalling aimed at adaptive changes in cell wall organization.

PMID- 17451451
TI  - Serotonin 5-HT(2C) receptors regulate anxiety-like behavior.
AB  - Central serotonin (5-hydroxytryptamine, 5-HT) systems have been implicated in the
      pathophysiology and treatment of anxiety disorders, which are among the world's
      most prevalent psychiatric conditions. Here, we report that the 5-HT(2C) receptor
      (5-HT(2C)R) subtype is critically involved in regulating behaviors characteristic
      of anxiety using male 5-HT(2C)R knockout (KO) mice. Specific neural substrates
      underlying the 5-HT(2C)R KO anxiolytic phenotype were investigated, and we report
      that 5-HT(2C)R KO mice display a selective blunting of extended amygdala
      corticotropin-releasing hormone neuronal activation in response to anxiety
      stimuli. These findings illustrate a mechanism through which 5-HT(2C)Rs affect
      anxiety-related behavior and provide insight into the neural circuitry mediating
      the complex psychological process of anxiety.

PMID- 17451452
TI  - Risk and protective haplotypes of the alpha-synuclein gene associated with
      Parkinson's disease differentially affect cognitive sequence learning.
AB  - Alpha-synuclein (SNCA) is a key factor in the regulation of dopaminergic
      transmission and is related to Parkinson's disease. In this study, we
      investigated the effects of risk and protective SNCA haplotypes associated with
      Parkinson's disease on cognitive sequence learning in 204 healthy volunteers. We
      found that the 3'-block risk SNCA haplotypes are associated with less effective
      stimulus-reward learning of sequences and with superior context representation of
      sequences. In contrast, participants with protective haplotypes exhibit better
      stimulus-reward learning and worse context representation, which suggest that
      these functions are inversely affected by risk and protective haplotypes. The
      Rep1 promoter polymorphism does not influence cognitive sequence learning.
      Because stimulus-reward learning may be mediated by the basal ganglia and context
      learning may be related to the medial temporal lobe, our data raise the
      possibility that dopaminergic signals regulated by SNCA inversely affect these
      memory systems.

PMID- 17451453
TI  - Association of the 54-nucleotide repeat polymorphism of hPer3 with heroin
      dependence in Han Chinese population.
AB  - Circadian clock genes have the function of producing circadian rhythm. They are
      also implicated in the origin or development of many diseases such as cancers and
      neuropsychiatric diseases. The purpose of this study is to determine whether the
      54-nucleotide repeat polymorphism of hPer3, one of the circadian clock genes,
      associates with heroin dependence. DNA samples were obtained from 209 Chinese
      heroin-dependent subjects and 249 Chinese healthy controls. The 54-nucleotide
      repeat polymorphism was detected by polymerase chain reaction and DNA agarose gel
      electrophoresis. The frequency of four-repeat allele was significantly higher
      (chi(2)= 10.64, P = 0.001; corrected for multiple tests, P = 0.003) in the mixed
      gender heroin-dependent subject group (four repeat: 0.89, five repeat: 0.11) than
      in the mixed gender control group (four repeat: 0.81, five repeat: 0.19); the
      frequency of four-repeat allele was also significantly higher (chi(2)= 10.00, P =
      0.002; corrected for multiple tests, P = 0.006) in the male heroin-dependent
      subject group (four repeat: 0.89, five repeat: 0.11) than in the male control
      group (four repeat: 0.81, five repeat: 0.19); for females, no significant trend
      was observed with the 54-nucleotide repeat polymorphism between the heroin
      dependent subject group and the control group. Our results suggest that the 54
      nucleotide repeat polymorphism of hPer3 significantly associates with heroin
      dependence at the allele frequency level and may be a potential risk factor for
      the development of heroin dependence.

PMID- 17451454
TI  - Dentine-bonded resin composite (Retroplast) for root-end filling: a prospective
      clinical and radiographic study with a mean follow-up period of 8 years.
AB  - AIM: To evaluate treatment outcome after using a resin composite (Retroplast, RP)
      in combination with a dentine-bonding agent (GLUMA) as root-end filling material
      after 1 year as well as after more than 5 years (final examination). Also, the
      influence of various pre-, intra- and postoperative factors on the treatment
      outcome was studied. METHODOLOGY: All patients (87) undergoing root-end resection
      consecutively treated by root-end filling with RP on an incisor, canine, pre
      molar, or first molar (87 teeth, 118 roots) were initially enrolled in the study.
      RP was applied on the entire resected surface that was prepared to a slightly
      concave shape and after conditioning with EDTA and GLUMA. The treatment outcome
      involving subjective, clinical and radiographic parameters was evaluated after 1
      year and at the final examination. A total of 27 patients (36 roots) were
      excluded from the study because of unavailability of follow-up (19) and
      extraction of the operated tooth for reasons other than failed surgery (8).
      Consequently, 60 patients (82 roots) were included in the final material. The
      mean follow-up period at the final examination was 8 years (range: 6.5-9 years).
      RESULTS: The radiographic evaluation at the final examination revealed that 77%,
      5%, 7% and 11% of the treated roots were characterized by complete, incomplete,
      uncertain and unsatisfactory healing, respectively. A total of 95% of the roots
      classified as completely healed at the 1-year control were also completely healed
      at the final examination. Two roots (5%) showing complete healing at the 1-year
      control revealed unsatisfactory healing at the final examination because of
      displaced or lost RP-filling. Moreover, 60% of the roots with uncertain healing
      at the 1-year control demonstrated complete or incomplete healing at the final
      examination. The classification according to subjective, clinical and
      radiographic parameters revealed that 78% of the teeth were characterized by a
      successful treatment outcome at the final examination. Evaluation of the
      influence of various pre-, intra- and postoperative factors on the treatment
      outcome revealed that the radiographic classification at the final examination
      was exclusively influenced by the radiographic classification at the 1-year
      control (P < 0.001). CONCLUSIONS: The present long-term study indicates that RP
      can be used for root-end filling with a successful treatment outcome.

PMID- 17451455
TI  - Radiological assessment of periapical status using the periapical index:
      comparison of periapical radiography and digital panoramic radiography.
AB  - AIM: To compare the use of periapical radiographs and digital panoramic images
      displayed on monitor and glossy paper in the assessment of the periapical status
      of the teeth using the periapical index (PAI). METHODOLOGY: A total of 86
      subjects were examined. All participants underwent a full-mouth radiographic
      survey (14 periapical radiographs) and a panoramic radiography. The periapical
      status, using the PAI score, of all appraised teeth was assessed. RESULTS:
      Periapical radiographs allowed the assessment of the periapical status of 87% of
      teeth using the PAI. On the contrary, digital radiography had a significantly
      reduced potential to allow assessment of the periapical status (P<0.01). Only
      57.6% and 34.1% of teeth could be appraised using digital panoramic images
      displayed on monitor and glossy paper respectively (P<0.01). The total percentage
      of teeth with periapical pathosis was five fold higher when assessed with digital
      panoramic images displayed on glossy paper compared with periapical radiographs
      (P<0.01). CONCLUSIONS: Teeth were best viewed on periapical radiographs except
      maxillary second and third molars, which were better viewed in orthopantomograms.
      Orthopantomograms on screen were scorable more often than when on printed images.
      Apical periodontitis was scored more often on paper than on screen, and more
      often on screen than in periapical radiographs.

PMID- 17451456
TI  - Carbon ion radiotherapy for vaginal malignant melanoma: a case report.
AB  - Malignant melanoma of the vagina is a very rare neoplasm and resistant to
      conventional radiotherapy. We report a case of vaginal malignant melanoma that
      was locally well controlled by carbon ion radiotherapy. A 55-year-old
      postmenopausal woman presented with abnormal vaginal bleeding. On pelvic and
      imaging examinations, an irregular mass of the posterior vaginal wall sized 7.5 x
      5 x 5 cm, an enlarged right inguinal lymph node, and two lung metastases were
      observed. Histologic diagnosis based on positive immunostaining for HMB-45 was
      malignant melanoma. She received dacarbazine-based chemotherapy and carbon ion
      radiotherapy for vaginal and inguinal tumor sites with 57.6 Gy equivalent dose
      per 16 fractions using five ports. Six months later, she was also given carbon
      ion radiotherapy for regrowing lung metastasis with 52.8 Gy equivalent dose per
      four fractions using four ports. She died 19 months after initial treatment due
      to brain metastases. The primary irradiated tumor disappeared completely 12
      months after initial treatment. The vaginal tumor, right inguinal lymph node, and
      lung tumor treated with carbon ion radiotherapy did not show any evidence of
      recurrence until her death. Carbon ion radiotherapy may be of value for vaginal
      malignant melanoma as a conservative approach.

PMID- 17451457
TI  - Assessment of cervical involvement in endometrial carcinoma by hysteroscopy and
      directed biopsy.
AB  - The objective of this study was to assess the diagnostic validity of hysteroscopy
      and directed biopsy for assessing cervical involvement in endometrial carcinoma.
      We conducted a study of 240 hysteroscopies and 44 cervical biopsies performed on
      240 patients with endometrial carcinoma between 2000 and 2005. Hysteroscopy
      results suggested cervical involvement in 55 cases, of which only 31 were
      confirmed (a subtotal hysterectomy was performed in two cases, and the resection
      margins were examined for tumor invasion). In the 31 patients with confirmed
      cervical involvement, 19 of the hysteroscopy-directed biopsies were positive, 3
      were negative, and 3 provided insufficient material. Six patients did not undergo
      biopsy. In the 24 patients with hysteroscopy false positive, 10 directed biopsies
      were positive and 9 were negative. Five patients did not undergo biopsy.
      Hysteroscopy suggested an absence of cervical involvement in 185 patients.
      Diagnosis was confirmed in 177 cases, and there were eight false negatives. In
      our case, office hysteroscopy proved to be a valid means of ruling out cervical
      involvement in endometrial carcinoma. However, it was not a valid means of
      detecting tumor involvement, even when combined with directed biopsy.

PMID- 17451459
TI  - Carcinosarcoma of the ovary.
AB  - The objective of this study was to evaluate the treatment and outcome in patients
      with ovarian carcinosarcoma. The Tumor Board Registry was reviewed for patients
      with ovarian carcinosarcoma treated at our institution from June 1993 to December
      2004. The medical records were retrospectively analyzed with emphasis on
      cytoreduction, cytotoxic regimens, progression-free interval, and survival.
      Twenty-two patients were identified. All but two presented with advanced stage
      disease. The median survival for the entire cohort was 38 months. Median survival
      was 46 months for 18 optimally debulked (<1 cm) patients and 27 months for four
      suboptimally debulked (>1 cm) patients. Six patients were treated with optimal
      cytoreduction and adjuvant cisplatin (40 mg/m(2)x 1 day) and ifosfamide (1200
      mg/m(2)/day x 4 days) every 28 days. Median progression-free interval in the
      cisplatin and ifosfamide group was 13 months, and median survival was 51 months.
      The combination of carboplatin (AUC 5) and taxol (175 mg/m(2)) every 21 days was
      administered to four patients as first-line chemotherapy following optimal
      cytoreduction. In the carboplatin and taxol group, median progression-free
      interval was 6 months and median survival was 38 months. The difference in
      survival between the cisplatin and ifosfamide group and the carboplatin and taxol
      group was not statistically significant (P= 0.48). In conclusion, patients with
      ovarian carcinosarcoma usually present with advanced stage disease. Treatment
      consists of optimal cytoreduction and chemotherapy. The most effective cytotoxic
      regimen remains to be determined. First-line cisplatin and ifosfamide or
      carboplatin and taxol can achieve survival rates observed in epithelial ovarian
      cancer.

PMID- 17451460
TI  - Application of laser capture microdissection and differential display technique
      for screening of pathogenic genes involved in endometrial carcinoma.
AB  - The objective is to eliminate the interference from other cell types; gene
      fragments involved in endometrial carcinoma (EC) are screened and cloned. Human
      normal endometrial glandular epithelia and EC cells were harvested with laser
      capture microdissection (LCM). The purification and concentration of minimal RNA
      were used to screen differential expressed gene fragments involved in EC by
      fluoro differential display polymerase chain reaction (FDD-PCR). The differential
      gene fragments were cloned, sequenced, and then identified by reverse Northern
      blot hybridization. Positive fragments were analyzed with basic local alignment
      search tool (BLAST). Cyclin-dependent kinase 7 (CDK7) expressions in EC and
      normal endometrial tissue were tested by immunohistochemical staining. Of 38
      differential bands, 3 bands were of high expression in normal endometrium and 35
      in EC. Six positive differential gene fragments were obtained and BLAST analysis
      for them suggested that L1.1 was homologous (99% identical) to the CDK7; L1.9 had
      a 99% homology with protein phosphatase 1 regulatory (inhibitor) subunit 12 A
      (PPP1R12A); L1.21 and L1.22 showed a 100% homology with cellular repressor of E1A
      stimulated genes 1 (CREG); and L1.25 and L1.26 indicated more than 98% homology
      with solute carrier family 39 (zinc transporter), member 10 (SLC39A10).
      Immunohistochemistry revealed that CDK7 expression was higher in EC than in
      normal endometrium. We conclude that pathogenic genes involved in EC are obtained
      with LCM and FDD-PCR. It has been first found that CDK7, PPP1R12A, CREG, and
      SLC39A10 are correlative with EC from gene level. CDK7 is strongly associated
      with EC and can be used as potential molecular marker of EC for further studies.

PMID- 17451461
TI  - HER-2/neu overexpression and amplification in uterine serous papillary carcinoma:
      comparative analysis of immunohistochemistry, real-time reverse transcription
      polymerase chain reaction, and fluorescence in situ hybridization.
AB  - Uterine serous papillary carcinoma (USPC) is a rare and highly malignant form of
      endometrial cancer (EC) characterized by early metastasis, chemoresistance, and
      high mortality rate. Little is known about USPC tumorigenesis even if recently a
      HER-2/neu role has been suggested in its development and progression. The aim of
      the present study was to evaluate HER-2 expression by immunohistochemistry (IHC)
      in 12 USPC formalin-fixed, paraffin-embedded (FFPE) samples. Moreover, we looked
      at the correlation between HER-2 protein expression and HER-2/neu gene
      amplification by fluorescence in situ hybridization (FISH), other than HER-2/neu
      messenger RNA expression by quantitative real-time reverse transcription (RT)
      polymerase chain reaction (PCR). Finally, these results have been compared with
      commonly evaluated clinical features in EC patients, in order to define the
      potential prognostic value of HER-2/neu overexpression in USPCs. A high
      expression of HER-2 protein by IHC was noted in 2 of 12 patients (16.6%), and the
      same cases showed specific HER-2/neu gene amplification by FISH. All the samples
      investigated displayed a perfect concordance between IHC and FISH data. Five
      (41.6%) of 12 tumors demonstrated polysomy of chromosome 17 and, focusing on the
      2 USPCs that showed HER-2/neu overexpression, one of them (50%) was polysomic for
      chromosome 17. All the other USPC cases (58.4%) showed to be disomic for
      chromosome 17. Quantitative RT real-time PCR performed on complementary DNA
      obtained from all FFPE USPC samples showed a complete correlation with FISH and
      IHC data. Moreover, HER-2/neu overexpression was associated with a poorer overall
      survival and a very low relapse-free survival time, thus being considered a
      candidate marker of worse overall prognosis in USPC. The use of trastuzumab
      (Herceptin), a monoclonal antibody directed against HER-2/neu, for the therapy of
      patients with HER-2/neu-positive USPCs should be further investigated in clinical
      trials.

PMID- 17451462
TI  - Acid sphingomyelinase inhibition suppresses lipopolysaccharide-mediated release
      of inflammatory cytokines from macrophages and protects against disease pathology
      in dextran sulphate sodium-induced colitis in mice.
AB  - Lipopolysaccharide (LPS) and inflammatory cytokines cause activation of
      sphingomyelinases (SMases) and subsequent hydrolysis of sphingomyelin (SM) to
      produce a lipid messenger ceramide. The design of SMase inhibitors may offer new
      therapies for the treatment of LPS- and cytokine-related inflammatory bowel
      disease. We synthesized a series of difluoromethylene analogues of SM (SMAs). We
      report here the effects of the most potent SMase inhibitor, SMA-7, on the LPS
      mediated release of tumour necrosis factor-alpha, interleukin-1beta and
      interleukin-6 from THP-1 macrophages and the pathology of dextran sulphate sodium
      (DSS)-induced colitis in mice. SMA-7 suppressed the LPS-induced cytokine release
      and nuclear factor-kappaB activation. LPS stimulation caused a four-fold increase
      in acid SMase activation, but little increase in neutral SMase activity. The
      presence of 10 microm SMA-7 caused acid SMase to remain at the control levels and
      reduced the formation of ceramide. HT-29 cells had significantly decreased cell
      viability when incubated with media from LPS-stimulated THP-1 macrophages.
      However, incubating the colon cells in media from both SMA-7 and LPS-treated
      macrophages caused little decrease in viability, suggesting that ceramide has a
      role in the LPS-stimulated signalling that releases cytotoxic factors against
      colon cells. Oral administration of SMA-7 to mice with 2% DSS in the drinking
      water, for 10 or 21 consecutive days, reduced significantly the cytokine levels
      in the colon and the severity of colonic injury. These findings suggest a central
      role for acid SMase/ceramide signalling in the pathology of DSS-induced colitis
      in mice, indicating a possible preventive or therapeutic role for SMase inhibitor
      in inflammatory bowel disease.

PMID- 17451463
TI  - Glucocorticoids exert opposing effects on macrophage function dependent on their
      concentration.
AB  - Glucocorticoids (GCs) are involved in the modulation of macrophage function and
      thereby control the host's immune responses to pathogens. However, neither the
      role of hormone concentration nor the differential contribution of the
      glucocorticoid (GR) and the mineralocorticoid receptors (MR) to these activities
      are known. Here we show that low levels of corticosterone enhance NO production
      as well as mRNA expression of pro-inflammatory cytokines, chemokines and enzymes
      required for mediator synthesis. In contrast, at high corticosterone
      concentrations macrophage function was strongly repressed. Importantly,
      inactivation of the GR by lentiviral delivery of siRNAs abrogated both the
      immunostimulatory and the immunosuppressive GC actions whereas inactivation of
      the MR had no effect. Furthermore, removal of endogenous GCs by adrenalectomy in
      vivo induced a preactivated state in macrophages that could be modulated by
      corticosterone. We conclude that GCs exert distinct effects on macrophage
      function dependent on their concentration, and that they primarily act through
      the GR despite concomitant expression of the MR.

PMID- 17451464
TI  - Live-attenuated influenza viruses as delivery vectors for Chlamydia vaccines.
AB  - Effective delivery systems are needed to design efficacious vaccines against the
      obligate intracellular bacterial pathogen, Chlamydia trachomatis. Potentially
      effective delivery vehicles should promote the induction of adequate levels of
      mucosal T-cell and antibody responses that mediate long-term protective immunity.
      Antigen targeting to the nasal-associated lymphoid tissue (NALT) is effective for
      inducing high levels of specific immune effectors in the genital mucosa, and
      therefore suitable for vaccine delivery against genital chlamydial infection. We
      tested the hypothesis that live attenuated influenza A viruses are effective
      viral vectors for intranasal delivery of subunit vaccines against genital
      chlamydial infection. Recombinant influenza A/PR8/34 (H1N1) viruses were
      generated by insertion of immunodominant T-cell epitopes from chlamydial major
      outer membrane protein into the stalk region of the neuraminidase gene.
      Intranasal immunization of mice with viral recombinants resulted in a strong T
      helper 1 (Th1) response against intact chlamydial elementary bodies. Also,
      immunized mice enjoyed a significant state of protective immunity (P > 0.002) by
      shedding less chlamydiae and rapidly clearing the infection. Furthermore, a high
      frequency of Chlamydia-specific Th1 was measured in the genital mucosal and
      systemic draining lymphoid tissues within 24 hr after challenge of vaccinated
      mice. Moreover, multiple epitope delivery provided a vaccine advantage over
      single recombinants. Besides, long-term protective immunity correlated with the
      preservation of a robustly high frequency of specific Th1 cells and elevated
      immunoglobulin G2a in genital secretions. Because live attenuated influenza virus
      vaccines are safe and acceptable for human use, they may provide a new and
      reliable approach to deliver efficacious vaccines against sexually transmitted
      diseases.

PMID- 17451465
TI  - Induction of potent cellular immune response in mice by hepatitis C virus NS3
      protein with double-stranded RNA.
AB  - Double-stranded RNA is produced during virus replication and, together with the
      viral antigen, is responsible for inducing host antivirus immunity. The hepatitis
      C virus (HCV) non-structural protein-3 (NS3) has been implicated in the immune
      evasion of HCV, and is one of the prime targets for inducing immunity against HCV
      infection. Mice were immunized with recombinant NS3 protein (rNS3) and poly (I:C)
      emulsified in Montanide ISA 720 (M720). Cytokine production was assayed by enzyme
      linked immunospot assay, and CD4(+) IFN-gamma(+) T helper (Th) cells or CD8(+)
      IFN-gamma(+) cytotoxic T lymphocytes were detected by flow cytometry. Anti-NS3
      titre and immunoglobulin G2a (IgG2a) and IgG1 levels were monitored by enzyme
      linked immunosorbent assay. Administration of rNS3 formulated in poly (I:C) and
      M720 induced anti-NS3 titres with a predominantly IgG2a isotype comparable to
      those induced by rNS3 in CpG-ODN and M720. The cytokine profiles showed that this
      formulation induced a Th1-biased immune response with several-fold more
      interferon-gamma (IFN-gamma)-producing cells than interleukin-4-producing cells.
      In contrast, rNS3 in M720 induced a Th2-biased immune response. The frequency of
      IFN-gamma-producing CD4(+) and CD8(+) cells induced by rNS3 in poly (I:C) and
      M720 was significantly higher than that induced by rNS3, rNS3 in M720, or rNS3 in
      poly (I:C), and was comparable to that induced by rNS3 in CpG-ODN with M720. The
      antigen-specific CD8(+) T-cell immune response persisted for up to 7 months after
      immunization. In conclusion, poly (I:C) with rNS3 in M720 can elicit a strong and
      persistent Th1-biased immune response and a cytotoxic T-lymphocyte response
      through cross-priming in mice. This study highlighted a promising formulation for
      inducing an efficient cellular immune response against HCV that has potential for
      HCV vaccine development.

PMID- 17451467
TI  - Obesity and the risk of appropriate defibrillator therapies in MADIT II trial.

PMID- 17451468
TI  - Healthcare resource utilization and costs associated with recurrent episodes of
      atrial fibrillation: the FRACTAL registry.
AB  - INTRODUCTION: Drivers of cost in the atrial fibrillation (AF) population are not
      fully understood. We sought to characterize the resource utilization and costs of
      treating new-onset AF, with emphasis on the incremental costs associated with
      recurrent episodes of AF over time. METHODS AND RESULTS: An inception cohort of
      973 AF patients was followed at 3-6 month intervals in an observational registry
      over a mean of 24 +/- 9 months. AF therapies, clinical outcomes, and both
      inpatient and outpatient medical resource utilization were tracked at each follow
      up interval. Registry patients were managed primarily with cardioversion and
      pharmacological therapy. Direct healthcare costs were calculated from a U.S.
      perspective by multiplying measures of resource utilization by representative
      price weights. Costs were compared among patients in whom the initial episode of
      AF became permanent and patients who initially achieved sinus rhythm and had
      either 0, 1-2, or > or = 3 documented recurrences during follow-up. Mean annual
      costs for these four groups were $2,372, $3,385, $6,331, and $10,312 per patient
      per year, respectively (P < 0.001 for trend), with the largest variation related
      to hospital costs. In multivariable analysis controlling for demographic
      characteristics and baseline cardiac and comorbid conditions, each documented
      recurrence of AF was found to increase annual healthcare costs by approximately
      $1,600. CONCLUSION: Following initial diagnosis, patients with AF treated with
      traditional therapies incur $4,000-$5,000 in annual direct healthcare costs.
      Costs are markedly higher in patients with multiple AF recurrences. These data
      may be helpful in evaluating the economic impact of new technologies for treating
      AF.

PMID- 17451469
TI  - Biventricular pacing and QT interval prolongation.
AB  - INTRODUCTION: The purpose of this study was to examine BiV pacing-dependent
      changes in QT interval and the related potential for proarrhythmia. Biventricular
      (BiV) pacing has emerged as a promising therapy for patients with advanced
      congestive heart failure (CHF) and bundle branch block (BBB). METHODS AND
      RESULTS: One hundred and seventy-six consecutive patients (123 men and 53 women;
      mean age 67 +/- 16 years) with ischemic (n = 128) or nonischemic (n = 48)
      cardiomyopathy in New York Heart Association Class II (8%) or III (92%) CHF
      (ejection fraction 24 +/- 9%) underwent atrial synchronous BiV pacing. The QRS,
      QT, and JT intervals were measured at 30 minutes after initiation of BiV pacing,
      at 24 hours, and at 1 month postimplant. QT interval was defined as the time
      interval between the initial deflection of the QRS complex and the point at which
      the T wave crossed the isoelectric line. At baseline, the average QRS duration
      was 178 +/- 10 ms, attributable to left BBB (n = 158) or intraventricular
      conduction delay (n = 18). BiV pacing resulted in a small but statistically
      significant reduction in QRS duration (148 +/- 9 ms during BiV pacing vs 178 +/-
      10 ms at baseline [P < 0.0001]), yet the QT increased to 470 +/- 34 ms with BiV
      pacing versus 445 +/- 32 ms at baseline [P < 0.0001]). The JTc interval during
      BiV pacing was significantly shorter than during LV pacing (290 +/- 9 ms vs 320
      +/- 20 ms, P < 0.0001). During a mean follow-up of 24 +/- 6 months, one patient
      developed recurrent torsade de pointes. That was eliminated once left ventricular
      pacing was discontinued. CONCLUSION: Biventricular pacing prolongs QT interval.
      However, the occurrence of torsade de pointes is uncommon.

PMID- 17451470
TI  - The testicular capsule and peritubular tissue of birds: morphometry, histology,
      ultrastructure and immunohistochemistry.
AB  - The testicular capsule was studied histologically, morphometrically,
      ultrastructurally and immunohistochemically in the Japanese quail, domestic fowl,
      turkey and duck (all members of the Galloanserae). The testicular capsule was,
      relative to mammals, thin, being 81.5 +/- 13.7 microm in the quail, 91.7 +/- 6.2
      microm in the domestic fowl, 104.5 +/- 29.8 microm in the turkey and 91.8 +/-
      18.9 microm in the duck. The orchido-epididymal border (hilus) of the capsule was
      much thicker than elsewhere in all birds (from 233.7 +/- 50.7 microm in the duck
      to 550.0 +/- 147.3 microm thick in the turkey). The testicular capsule, other
      than the tunica serosa and tunica vasculosa, comprised, in the main, smooth
      muscle-like or myoid cells running mainly in one direction, and disposed in one
      main mass. Peritubular tissue was similarly composed of smooth muscle-like cells
      disposed in several layers. Actin and desmin intermediate filaments were
      immunolocalized in the inner cellular layers of the capsule in the quail,
      domestic fowl and duck, but uniformly in the turkey. Vimentin intermediate
      filament immunoreaction in the capsule was moderately and uniformly positive in
      the testicular capsule of only the quail. Actin and desmin, but not vimentin
      (except very faintly in the turkey) or cytokeratin, were immunolocalized in the
      peritubular tissue of all birds. The results therefore establish, or complement,
      some previous observations that these birds have contractile cells in their
      testicular capsule and peritubular tissue, whose function probably includes the
      transport of testicular fluid into the excurrent duct system.

PMID- 17451472
TI  - A simplified guide for arranging 30 degrees Pilkington Turner posterior denture
      teeth in a balanced occlusion.
AB  - A simple technique is presented for achieving balanced occlusion when setting 30
      degrees Pilkington-Turner teeth. This technique involves the rotation of the
      mandibular posterior teeth around three axes: the vertical axis, to align the
      grooves and embrasures with the lateral path of the movement of the cusps; the
      mesio-distal axis, to achieve the Curve of Wilson; and the bucco-lingual axis,
      resulting in the Curve of Spee.

PMID- 17451471
TI  - Craniofacial growth in fetal Tarsius bancanus: brains, eyes and nasal septa.
AB  - The tarsier skull has been of particular interest in studies of primate taxonomy
      and functional morphology for several decades. Despite this, there remains no
      comprehensive data on how the tarsier skull develops, especially in relation to
      the soft-tissues of the head. Here we have documented for the first time fetal
      development of the skull and brain as well as the nasal septum and eyes in T.
      bancanus. We have also tested for the possible influence of these tissues in
      shaping skull architecture. Nineteen post-mortem specimens were imaged using high
      resolution magnetic resonance imaging and magnetic resonance microscopy.
      Landmarks and volume data were collected and analysed. Findings demonstrated
      massive increases of brain size and eye size as well as flattening of the midline
      cranial base, facial projection and orbital margin frontation. Little evidence
      was found to support the notion that growth of the brain or nasal septum
      physically drives the observed changes of the skull. However, increases in the
      size of the eyes relative to skull size were associated with orbital margin
      frontation. With the possible exception of the results for eye size, the findings
      indicate that rather than forcing change the soft-tissues form a framework that
      physically constrains the morphogenetic template of the skeletal elements. This
      suggests, for example, that the degree of cranial base angulation seen in
      adulthood is not directly determined by brain expansion bending the basicranium,
      but by brain enlargement limiting the extent of cranial base flattening
      (retroflexion) in the fetus.

PMID- 17451473
TI  - The Integrated Abutment Crownt, a screwless and cementless restoration for single
      tooth implants: a report on a new technique.
AB  - A technique is presented for the restoration of single-tooth, implant-supported
      crowns where the abutment and the crown material are chemomechanically bonded;
      therefore, there is no need for cement, and the implant and implant-abutment are
      connected with a screwless locking-taper. The clinical and laboratory procedures
      involved in the fabrication and insertion of the restoration are described in
      detail. This restoration offers the restorative dentist some advantages:
      excellent marginal adaptation with a cementless interface, a bacterially sealed
      implant-abutment connection, a crown material with a similar wear rate and
      hardness values of human enamel, a simple laboratory technique, and a reduced
      number of prosthetic components. Due to the light-cured nature of the crown
      material, chairside modifications can be accomplished. The major drawbacks are:
      studies are necessary to assess the long-term performance of the Integrated
      Abutment Crown (IAC)'s in both anterior and posterior areas of the mouth. Resin
      materials have higher roughness values, accumulate plaque at a higher rate, and
      are more likely to stain than tooth structure and all-ceramic restorations.

PMID- 17451475
TI  - Rehabilitation of the edentulous maxilla after the failure of an implant
      supported bar.
AB  - Dental implants provide patients with multiple restorative options for the
      complete edentulous maxilla. This article describes a technique for restoration
      of the edentulous maxilla with a tissue-implant-supported overdenture after the
      mechanical failure of an implant-supported bar. This technique allows the
      clinician to use the existing restoration with better distribution of the
      occlusal load between the implants and the supporting tissues.

PMID- 17451474
TI  - A dual impression technique for implant overdentures.
AB  - This article describes a technique for a two-stage selective pressure impression
      with a custom tray for implant-retained, tissue-supported overdentures.

PMID- 17451476
TI  - Factors affecting the strength of denture repairs.
AB  - Fracture of dentures is a common clinical finding in daily prosthodontic
      practice, resulting in great inconvenience to both patient and dentist. A
      satisfactory repair should be cost-effective, simple to perform, and quick; it
      should also match the original color and not cause distortion to the existing
      denture. Different repair materials, surface designs, and mechanical and chemical
      surface treatments have been recommended in order to obtain stronger repairs.
      This article reviews some of the available literature with regard to the most
      important factors that may influence the strength of denture repairs.

PMID- 17451477
TI  - Restoration of the partially dentate patient with conventional fixed and
      removable prostheses.
AB  - This clinical report documents the treatment of a 65-year-old Caucasian female
      referred for fixed and removable partial denture fabrication following completion
      of her orthodontic treatment.

PMID- 17451478
TI  - Optimization of tooth color and shade guide design.
AB  - PURPOSE: One critical prerequisite for dental shade guides is to match the color
      range and distribution of human teeth. The purpose of this study was to design
      computer models for dental shade guides and compare them with an existing shade
      guide. A targeted coverage error for a newly developed shade guide was DeltaE(ab)
      < 2 with a corresponding CIE2000 value. MATERIALS AND METHODS: A total of 1064
      teeth were evaluated in vivo using an intra-oral spectrophotometer. Shade guide
      models were designed using different methods for representation of the data set,
      hierarchical clustering, and nonlinear constrained optimization. Coverage error
      was calculated for both CIELAB and CIE2000 values. Recorded values were compared
      with coverage error of Vitapan Classical (VC) shade guide. Wilcoxon signed-rank
      test for paired samples and linear regression were used in statistical analysis.
      RESULTS: Coverage error of VC was 4.1 (SD 1.8), ranging from 0.5 to 11.5
      DeltaE(ab). Group A shades had the best match for human teeth (43.9%) followed by
      Groups C (24.1%), B (20.4%), and D (11.7%) shades, respectively. CIELAB coverage
      error of the newly designed 24-tab shade guide using clustering and optimization
      was 2.05 (0.95) and 1.96 (0.92), respectively. Corresponding CIE2000 coverage
      error values were 1.43 (0.68) and 1.40 (0.65), respectively. A significant
      difference between results obtained using clustering and optimization was
      determined. CIELAB color differences were greater, but highly correlated as
      compared with their CIE2000 counterparts (DeltaE(00)= 0.64 x DeltaE(76)+ 0.13, r
      > 0.99). DISCUSSION: This study demonstrated that, compared with existing shade
      guides, future shade guides can provide either (a) similar coverage of tooth
      color with fewer tabs, thus simplifying shade matching procedure, or (b) better
      coverage of tooth color with a similar number of tabs, in both cases increasing
      the chances of satisfactory matches and, consequently, better esthetics.
      CONCLUSIONS: Both clustering and optimization enabled better representation of
      tooth color as compared with an existing dental shade guide. Optimization
      outperformed clustering and is therefore recommended as a method of choice for
      representation of tooth color and designing of dental shade guides.

PMID- 17451479
TI  - The effect of water immersion on the shear bond strength between chairside reline
      and denture base acrylic resins.
AB  - PURPOSE: The effect of water immersion on the shear bond strength (SBS) between 1
      heat-polymerizing acrylic resin (Lucitone 550-L) and 4 autopolymerizing reline
      resins (Kooliner-K, New Truliner-N, Tokuso Rebase Fast-T, Ufi Gel Hard-U) was
      investigated. Specimens relined with resin L were also evaluated. MATERIALS AND
      METHODS: One hundred sixty cylinders (20 x 20 mm) of L denture base resin were
      processed, and the reline resins were packed on the prepared bonding surfaces
      using a split-mold (3.5 x 5.0 mm). Shear tests (0.5 mm/min) were performed on the
      specimens (n = 8) after polymerization (control), and after immersion in water at
      37 degrees C for 7, 90, and 180 days. All fractured surfaces were examined by
      scanning electron microscopy (SEM) to calculate the percentage of cohesive
      fracture (PCF). Shear data were analyzed with 2-way ANOVA and Tukey's test;
      Kruskall-Wallis test was used to analyze PCF data (alpha= 0.05). RESULTS: After
      90 days water immersion, an increase in the mean SBS was observed for U (11.13 to
      16.53 MPa; p < 0.001) and T (9.08 to 13.24 MPa, p= 0.035), whereas resin L showed
      a decrease (21.74 MPa to 14.96 MPa; p < 0.001). The SBS of resins K (8.44 MPa)
      and N (7.98 MPa) remained unaffected. The mean PCF was lower than 32.6% for K, N,
      and T, and higher than 65.6% for U and L. CONCLUSIONS: Long-term water immersion
      did not adversely affect the bond of materials K, N, T, and U and decreased the
      values of resin L. Materials L and U failed cohesively, and K, N, and T failed
      adhesively.

PMID- 17451480
TI  - Effect of different finishing and polishing agents on the surface roughness of
      cast pure titanium.
AB  - PURPOSE: The aim of this study was to evaluate the effect of finishing and
      polishing agents on surface roughness of cast commercially pure titanium using
      scanning electron microscope (SEM) analysis. MATERIALS AND METHODS: A
      standardized square steel die measuring 10 x 10 mm with a thickness of 2 mm was
      machine cut. An impression of this die was used to create wax patterns for
      casting. Sixty specimens were cast in commercially pure titanium. These were
      divided into three groups (A, B, and C) of 20 specimens each. Group A specimens
      were polished with black, brown, and green rubber discs followed by green
      polishing compound with buff. Group B specimens were polished with black, brown,
      and green rubber cones, buffed with yellow polishing cake designed for gold
      alloy. Group C specimens were polished with silicium carbide cones and buffed
      with orange polishing cake. Surface roughness of the test specimens was measured
      in microns with a perthometer. Data were analyzed with ANOVA and Tukey's honest
      significant difference (HSD) multiple comparison tests among the different
      groups. Qualitative analysis was done by SEM photomicrographs. RESULTS: Surface
      roughness values R(a) for Groups A, B, and C were 0.68 microm, 0.78 microm, and
      0.27 microm, respectively. SEM photomicrographs and the statistical analysis
      revealed that the finishing and polishing were better with Group C test specimens
      with lower surface roughness values compared with groups A and B. Tests showed
      that Group C was statistically smoother (p< or = 0.01). CONCLUSION: Within the
      limitations of this study, surface roughness was less on cast CpTi specimens that
      were finished and polished from the cutters designed specifically for titanium.

PMID- 17451481
TI  - Precision of fit of two margin designs for metal-ceramic crowns.
AB  - STATEMENT OF PROBLEM: Although metal-ceramic restorations are widely used, there
      is a lack of information about how the fit is affected by margin designs.
      PURPOSE: This study measured and compared the precision of fit of metal-ceramic
      crowns with two margin designs. MATERIAL AND METHODS: Thirty-two extracted human
      premolar teeth were prepared for complete-coverage restorations with an
      internally rounded shoulder preparation. Impressions were made from all teeth,
      and master dies were poured with improved stone type V. MC crowns were fabricated
      with a porcelain-butt margin on the buccal aspect (n = 32) and a feather-edge
      metal margin on the lingual aspect (n = 32), which served as a control group.
      Precision of fit was measured three times at the mid-buccal and mid-lingual
      margins of each crown with a profilometer. The data were statistically analyzed
      with the paired t-test (alpha < .05). RESULTS: Mean marginal gap size of
      porcelain-butt margins was 27.93 microm (+/-15.84) and of feather-edge metal
      margins 42.43 microm (+/-24.12). The marginal gap size of feather-edge metal
      margins was statistically significantly greater than that of porcelain-butt
      margins (p = 0.0045). CONCLUSION: The marginal fit of porcelain-butt margins was
      significantly better than that of feather-edge metal margins. CLINICAL
      IMPLICATIONS: Porcelain-butt margins in this study had a better marginal fit than
      feather-edge metal margins, and thus have given clinicians evidence to prefer the
      use of porcelain-butt margins.

PMID- 17451482
TI  - A quality assessment of the casting process on magnetic keepers.
AB  - PURPOSE: The objective of this study was to qualitatively investigate the effect
      of the burn-out (mold) temperature, investment material, and casting alloy on the
      surface integrity of the Magfit EX keeper. MATERIALS AND METHODS: Forty-two
      Magfit EX keepers were waxed-up, invested in five investment materials (Beauty
      Cast, Cristobalite, CM-10, Cera-Fina, Castorit-super), and subjected to burn-out
      temperatures ranging from 450 to 700 degrees C at intervals of 50 degrees C. The
      keeper samples were then cast into copings with three alloys (Castwell, Protor 3,
      Optimum) under standard conditions. The keeper surfaces were then examined under
      a microscope, and the compositions were assessed by an X-ray micro-analyzer in a
      scanning electron microscope (SEM). A new keeper served as control. RESULTS: At a
      burn-out temperature of 550 degrees C, the keeper surface started to
      disintegrate. X-ray micro-analysis showed an increase in oxygen content with
      increasing temperature. At 700 degrees C, the keeper surface disintegrated, and
      the composition differed markedly from that of the new keeper. The keeper
      surfaces were intact with all investments except those with Beauty-Cast. The
      keeper surfaces were found to be damaged when the casting alloy was Optimum.
      CONCLUSIONS: Beauty-Cast investment with a burn-out temperature of 700 degrees C
      is unsuitable for casting the Magfit EX keeper-coping unit. Also, high fusing
      alloys are not recommended for casting Magfit EX keepers.

PMID- 17451483
TI  - Depression in Dhat syndrome.
AB  - AIMS AND OBJECTIVES: Dhat syndrome is a widely recognized clinical condition in
      the Indian subcontinent characterized by excessive preoccupation with semen loss
      as the main presenting complaint. This condition has been considered to be a
      culture-bound syndrome, and depressive symptoms have previously been reported. We
      were interested to know how common depression is, and to quantify these features.
      MATERIALS AND METHODS: We studied 30 patients attending the Psychiatry Outpatient
      Department of a tertiary care hospital for their complaints about passing of
      semen in urine frequently. Those with depressive symptoms were further evaluated
      using the fourth revision of the Diagnostic and Statistical Manual of Mental
      Disorders (DSM-IV) Diagnostic Criteria for Depression, and depression severity
      was assessed using the 17-item Hamilton Depression Rating Scale for Depression
      (HAM-D). Patients meeting the criteria were started on capsule fluoxetine, a
      selective serotonin reuptake inhibitor, in dose of 20-40 mg per day. Patients
      were periodically followed fortnightly and were reevaluated for therapeutic
      response using the HAM-D. RESULTS: A total of 30 patients (age = 20-40 years;
      mean age = 29 years; mean age of onset = 19 years; mean duration of illness = 11
      months) were studied. The majority of cases were unmarried (64.2%) and educated
      till 5th class or above (70%). Twenty out of 30 (66%) patients met DSM-IV
      Diagnostic Criteria for Depression. Ten patients (33.3%) were found to have a
      comorbid problem of premature ejaculation, and two patients reported erectile
      dysfunction (6.6%). Patients showed statistically significant therapeutic
      response to fluoxetine. CONCLUSION: Depressive phenomenology meeting DSM-IV
      Diagnostic Criteria for Depression seems common in Dhat syndrome and responds to
      selective serotonin reuptake inhibitors along with regular counseling.

PMID- 17451484
TI  - Development of feminizing genitoplasty for gender dysphoria.
AB  - INTRODUCTION: Determining the history and development of feminizing genitoplasty
      is fascinating and instructive but fraught with difficulty. Earliest examples
      relate to practices carried out in ancient cultures. Gender reassignment surgery
      (GRS) developed from reconstructive procedures for congenital abnormalities. Some
      surgery was disguised, techniques were not recorded, and operations were carried
      out in secret. AIM: The aim of this article is to review the historical
      development of male-to-female GRS. METHODS: Information was gleaned from Medline
      and general Internet searches. Further evidence was found by reviewing the
      references of early articles. A fascinating insight was also found in the
      autobiographies of GRS patients. RESULTS: The first recorded case was by Abrahams
      in 1931. Techniques evolved from the early vaginal absence work of Beck and
      Graves. Pioneers of GRS were Sir Harold Gillies in England and Georges Burou of
      Casablanca. In the 1950s, they both used invagination of the penile skin sheath
      to form a vagina. Howard Jones, of Johns Hopkins, published the second classic
      technique using penile and scrotal skin flaps. These two methods form the basis
      of male-to-female GRS today. The history of GRS reveals a struggle to improve
      functionality as well as cosmesis. In particular, the neovagina but also a
      functioning neoclitoris, which has developed from a cosmetic swelling into an
      innovated organ, derived from the glans penis and harvested penile neurovascular
      bundle. CONCLUSIONS: Improved function and cosmesis continue to be the aim of the
      gender dysphoria surgeon. However, this review suggests the future management of
      transwomen should address not only refinements of surgical techniques but also
      prospective collection of posttreatment quality-of-life issues.

PMID- 17451485
TI  - Does mode of delivery affect sexual functioning of the man partner?
AB  - INTRODUCTION: Recent surveys showed that the major reasons for avoiding vaginal
      delivery were the fear of childbirth and the concern for postpartum sexual
      health. Although sexual dysfunction is a disorder that affects a couple rather
      than an individual, all studies investigating the relationship between the mode
      of delivery and sexual problems have been conducted only in cohorts of women.
      AIM: To determine the effect of mode of delivery on quality of sexual relations
      and sexual functioning of men by using the Golombock-Rust Inventory of Sexual
      Satisfaction (GRISS). MAIN OUTCOME MEASURE: Mean score of sexual function and
      prevalence of sexual dysfunction in overall and specific areas of the GRISS were
      compared among the three groups. METHODS: A total of 107 men accompanying their
      wives in outpatient clinics of obstetrics and gynecology met inclusion/exclusion
      criteria. Three groups of men were defined; men whose partners had: (i) "elective
      cesarean delivery" (N = 21; mean age 32.2 +/- 3.8 years); (ii) "vaginal delivery
      with mediolateral episiotomy" (N = 36; mean age 31.4 +/- 4.5 years); and (iii)
      "not given birth" (N = 50; mean age 28.8 +/- 4.0 years). RESULTS: Mean overall
      sexual function score (normal value < 25 points) was 20.5 +/- 8.2 in the elective
      caesarean group, 19.3 +/- 6.5 in the vaginal delivery group, and 18.8 +/- 9.3 in
      the nulliparae group (P = 0.731). Prevalence of sexual dysfunction in men was
      28.6% in the elective caesarean group, 19.4% in the vaginal delivery group, and
      30.0% in the nulliparae group (P = 0.526). CONCLUSION: Overall sexual function of
      men was not affected by their partner's parity and mode of delivery. An elective
      cesarean section simply because of concerns about sexual function would not
      provide additional benefit to men, and could deny women a possible vaginal
      delivery, which is generally assumed to be safer than cesarean section.

PMID- 17451486
TI  - Frenular grafting: an alternative to circumcision in men with a combination of
      tight frenulum and phimosis.
AB  - INTRODUCTION: Men suffering from frenular scarring and stricturing with
      associated phimosis are traditionally treated with circumcision. In men wishing
      to retain their foreskin, the treatment options are limited by this dual
      pathology. Frenuloplasty alone is contraindicated in this clinical setting. AIM:
      To demonstrate the utility of frenular grafting in patients with a tight frenulum
      and concomitant phimosis who wish to retain their foreskin. METHODS: Six men were
      included in the study. Presenting symptoms included bleeding (N = 2) and
      pain/phimosis (N = 6). Median age is 27 years (25-34 years). All men were healthy
      and sexually active. We describe a refined technique involving the excision of
      scarred and redundant frenular tissue and the insertion of a skin graft to the
      area. MAIN OUTCOME MEASURES: All patients were assessed for graft viability,
      functional/symptom improvement, time to penetrative intercourse, and overall
      satisfaction. RESULTS: All men received an interposition skin graft with 100%
      viability, with no revision surgery required. Postoperatively, all men were
      sexually active and able to retract their foreskin. CONCLUSIONS: Cosmetic
      outcomes are encouraging and painless sexual intercourse is attainable in this
      difficult group of patients.

PMID- 17451487
TI  - Role of postcircumcision mucosal cuff length in lifelong premature ejaculation: a
      pilot study.
AB  - INTRODUCTION: Premature ejaculation (PE) is the most prevalent sexual dysfunction
      among men. Several theories about its etiology have been made. One of the
      conflicting factors is the effect of circumcision on ejaculation, and there are
      some concerns about leaving so much mucosa during circumcision. AIM: In our study
      the relationship between mucosal cuff length and PE was investigated. METHODS:
      Eighty-four circumcised men were studied, including 42 men with PE and 42 men
      without. The following data and measurements were investigated: age, education,
      smoking, intravaginal ejaculation latency time (IELT), circumcision timing,
      stretched penile, penile skin, and mucosal cuff lengths. MAIN OUTCOME MEASURE:
      Penile, mucosal cuff, and penile skin lengths, the IELT. RESULTS: The mean
      penile, mucosal cuff, and penile skin lengths were 121.1 +/- 12.8, 15.4 +/- 4.8,
      and 80.8 +/- 21.0 mm in PE men, respectively, and were 130.1 +/- 10.4, 14.7 +/-
      3.4, and 88.7 +/- 12.2 mm in the control group, respectively. No statistically
      significant differences were seen regarding the length of the penis (P = 0.80),
      mucosal cuff (P = 0.84), and penile skin (P = 0.99). The two groups were not
      different regarding education (P = 0.90), smoking (P = 0.70), and circumcision
      timing (P = 0.65). CONCLUSION: Postcircumcision mucosal cuff length is not a risk
      factor for PE.

PMID- 17451488
TI  - New-onset priapism associated with ingestion of terazosin in an otherwise healthy
      man.
AB  - INTRODUCTION: Priapism has been reported as a rare effect of the commonly used
      alpha 1-antagonists through direct inhibition of the sympathetic input necessary
      for detumescence. Although previously reported as an adverse event in a patient
      with spinal cord injury, to the best of our knowledge, terazosin-induced priapism
      in an otherwise healthy man has not been previously described. AIM: We describe
      an otherwise healthy man with lower urinary symptoms who developed priapism after
      ingestion of the commonly prescribed alpha-blocker terazosin. RESULTS: The
      priapism resolved after a combination of cavernosal aspiration and alpha-agonist
      administration. CONCLUSION: Priapism is an extremely rare side effect of alpha
      blocker therapy and has previously been described in association with other alpha
      blockers, as well as with terazosin, in a spinal cord-injured patient. We report
      a case of priapism specifically associated with terazosin prescribed for lower
      urinary tract symptoms in an otherwise healthy man.

PMID- 17451489
TI  - Sexual function in female patients with unstable angina or non-ST-elevation
      myocardial infarction.
AB  - INTRODUCTION: Coronary artery disease is the leading cause of death and
      disability for both women and men. The psychological impact of acute myocardial
      infarction, as well as the physiological effects of the illness and its
      medications, can have a major effect on a patient's ability to resume sexual
      activity. AIM: To assess sexual activity in female patients with unstable angina
      or non-ST-elevation myocardial infarction (NSTEMI), and to study the impact of
      cardiovascular rehabilitation (CR) on resumption of sexual activity. MAIN OUTCOME
      MEASURES: Doppler-echocardiographic study, exercise tolerance test (ETT), and
      assessment of sexual activity. METHODS: This study was conducted in the Riyadh
      National Hospital and included 35 female patients admitted to the intensive care
      unit for management of unstable angina or NSTEMI. All patients were enrolled into
      a CR program. All of them were interviewed for assessment of sexual activity, 12
      weeks post discharge. The Arizona Sexual Experience Scale (ASEX) was used for the
      assessment of the severity of sexual dysfunction for patients who resumed their
      sexual activity. RESULTS: Results indicate that 48.57% of the patients resumed
      their sexual activity at the time of the interview. However, most of them were
      either not satisfied at all with their sexual activity or mostly dissatisfied.
      The remaining patients (51.43%) had not resumed sex yet. CR was completed by
      70.59% of those resuming sex, and 38.89% of those not resuming sex. We estimated
      that rehabilitated patients were 3.77 times more likely to resume sexual activity
      than those who did not receive rehabilitation. ASEX score ranged from 19 to 30,
      with a mean of 24.118 +/- 3.42. CONCLUSION: Unstable angina and NSTEMI have a
      negative impact on frequency of, and satisfaction with, sexual activity, and lead
      to sexual dysfunction within a large number of female patients. Accurate and
      complete sexual instructions for both partners with specific attention paid to
      the woman's concerns and needs should be part of CR programs.

PMID- 17451490
TI  - Predictors of sexual and relationship functioning in couples with Chronic
      Prostatitis/Chronic Pelvic Pain Syndrome.
AB  - INTRODUCTION: Both partners in a relationship are typically affected when one
      experiences sexual dysfunction and/or pain. However, couple functioning has
      rarely been investigated in Chronic Prostatitis/Chronic Pelvic Pain Syndrome
      (CP/CPPS), a common condition in men involving pelvic pain and sexual
      dysfunction. AIM: To identify potential predictors of sexual and relationship
      function among couples with CP/CPPS, and to examine associations among pain,
      sexual, and relationship variables in patients and their women partners. METHODS:
      Thirty-eight patients with CP/CPPS and their women partners completed
      questionnaires assessing sexual and relationship function via mail. MAIN OUTCOME
      MEASURES: Patients completed a subscale from the Multidimensional Pain Inventory
      and the International Index of Erectile Function. Partners completed the Female
      Sexual Function Index. All participants completed the Golombok-Rust Inventory of
      Sexual Satisfaction and the Dyadic Adjustment Scale. RESULTS: Couples' sexual
      function, sexual satisfaction, and relationship adjustment were all significantly
      associated. Pain severity significantly predicted sexual and relationship
      functioning among couples. However, multiple regression models revealed that
      sexual and relationship variables were the strongest predictors of patient and
      partner functioning, over and above pain severity. Patient sexual function was
      predicted by patient sexual satisfaction and female sexual function, whereas
      female sexual function was predicted by female sexual satisfaction and patient
      relationship adjustment. With regard to sexual satisfaction, patient sexual
      function and relationship adjustment and female relationship adjustment predicted
      patient sexual satisfaction. Female sexual function predicted female sexual
      satisfaction. Among both patients and partners, relationship adjustment was
      significantly predicted by that of one's partner. The only partner variable that
      was significantly predicted by patient pain severity was female sexual function.
      CONCLUSIONS: Significant links exist among the sexual and relationship
      functioning of patients with CP/CPPS and their partners. These results emphasize
      the importance of the interpersonal context on couples' functioning, and
      highlight the need to adopt a biopsychosocial approach when investigating
      CP/CPPS.

PMID- 17451491
TI  - Resistance to root-knot nematode in tomato roots expressing a nematicidal
      Bacillus thuringiensis crystal protein.
AB  - Our laboratory has demonstrated previously that Bacillus thuringiensis (Bt)
      crystal (Cry) proteins present in the Cry5 and Cry6 subclades intoxicate free
      living nematodes. In this study, we tested whether the expression of nematicidal
      Cry6A in transgenic plants provided protection against plant-parasitic nematodes.
      As bacterial codon usage is incompatible with expression in plants, two different
      codon-modified cry6A genes were synthesized for expression in plants. One was
      designed by maintaining codon diversity whilst removing codons not common in
      plants, and the other was designed by selecting the optimal codon for each amino
      acid based on the Arabidopsis genome. Both versions of the cry6A gene, driven by
      the constitutive cauliflower mosaic virus 35S promoter, were introduced into
      tomato roots via Agrobacterium rhizogenes. Although both were found to express
      Cry6A protein, the codon diversity gene generated superior expression. These
      Cry6A-expressing roots were then challenged with root-knot nematode, Meloidogyne
      incognita. Three different infection parameters were compared between Cry6A
      expressing roots and control roots transformed with empty vector or green
      fluorescent protein (GFP). These data demonstrated that M. incognita was able to
      ingest the 54-kDa Cry6A, and that Cry6A intoxicated the parasitic nematode, as
      indicated by a decrease in progeny production of up to fourfold. These results
      indicate, for the first time, that a Bt Cry protein can confer plant resistance
      to an endoparasitic nematode, and that Cry proteins have the potential to control
      plant-parasitic nematodes in transgenic plants.

PMID- 17451492
TI  - Cue- versus response-locked processes in backward inhibition: evidence from ERPs.
AB  - A task set may need to be inhibited to facilitate the switch to another task.
      This event-related potential (ERP) study determined (1) whether backward
      inhibition (BI) is exerted preferentially in high interference environments, and
      (2) whether ERPs locked to critical time points reflect BI during cue preparation
      and/or response stages. High interference (HI) and low interference (LI) were
      created by manipulating task difficulty. A reaction time (RT) BI effect (i.e.,
      BI>control trials) was shown only during HI tasks. Cue-locked ERPs on LI tasks
      suggest increased attentional resources were allocated during the reactivation of
      a recently inhibited task. For HI tasks, BI versus control trial differences were
      reflected in a response-locked ERP negativity only after response selection
      (indexed by the response-locked lateralized readiness potential), indicating that
      BI is a lateral inhibition mechanism exerted during response preparation.

PMID- 17451493
TI  - Discontinuous presentation of ambiguous figures: how interstimulus-interval
      durations affect reversal dynamics and ERPs.
AB  - If we observe an ambiguous figure, our percept is unstable and alternates between
      the possible interpretations. Periodically interrupting the presentation sizably
      modulates the spontaneous reversal rate. We here studied event-related potential
      (ERP) correlates of the neural processes underlying these strong modulations. An
      ambiguous Necker stimulus was presented discontinuously with four randomly
      varying interstimulus intervals (ISI; 14, 43, 130, 390 ms) while participants
      indicated perceptual reversals. EEG was selectively averaged with respect to the
      participants' percept and ISI. ERP traces varied markedly between ISIs. A simple
      model explained a major part of this variation and showed that the ISI-dependent
      ERP modulation occurs after disambiguation has already taken place. We suggest
      that perceptual stability (or reversal) depends on a system state, slowly
      changing from one reversal to the next. ISI can shift this state on a scale
      between stability and instability.

PMID- 17451494
TI  - Plasma colloid osmotic pressure and total protein trends in horses during
      anesthesia.
AB  - OBJECTIVE: To investigate the changes in colloid osmotic pressure (COP) and total
      protein concentrations during routine general anesthesia in horses. STUDY DESIGN:
      Prospective, clinical study. ANIMALS: Twelve adult healthy horses aged 9.1 +/-
      4.7 years and weighing 474 +/- 79 kg presented for elective surgery and 14 adult
      horses aged 8.7 +/- 7.3 years and weighing 510 +/- 85 kg. METHODS: All horses
      were premedicated with xylazine and anesthesia induced with ketamine, diazepam
      and guaifenesin, and maintained with isoflurane for 2.5 hours. Lactate Ringer's
      solution was administered at 11 mL kg(-1) hour(-1). Osmolality, COP,
      electrolytes, glucose, and lactate were measured with specific commercial
      analyzers. Total protein (TP) was determined with a refractometer and packed cell
      volume with centrifuged capillary tubes. In the second group of 14 horses samples
      were taken from both venous and arterial sites simultaneously and the above
      measurements performed. RESULTS: Before anesthesia, COP and TP were 22.2 +/- 2
      mmHg and 6.9 +/- 0.4 g dL(-1), respectively. Within 15 minutes of anesthetic
      induction, COP and TP decreased significantly (19.9 +/- 1.9 mmHg and 6.3 +/- 1.9
      g dL(-1); p < 0.01). During anesthesia COP and TP decreased in a linear form (COP
      r2 = 0.96 and TP r2 = 0.97). The COP and TP were 15 +/- 1.3 mmHg and 5.1 +/- 0.2
      g dL(-1) at the end of anesthesia. Calculation of COP from TP values failed to
      accurately predict measured COP. Simultaneous arterial and venous samples in the
      14 anesthetized horses yielded no differences for COP or TP. CONCLUSIONS AND
      CLINICAL RELEVANCE: The data indicate that COP, like TP, decreases over the
      course of routine anesthetic management of horses and venous versus arterial
      samples should reveal comparable information.

PMID- 17451495
TI  - Effects of intravenous butorphanol on cardiopulmonary function in isoflurane
      anesthetized alpacas.
AB  - OBJECTIVE: To determine the effects of intravenous (IV) butorphanol on the
      cardiopulmonary system and on the bispectral index (BIS) in isoflurane
      anesthetized alpacas. STUDY DESIGN: Randomized, blinded cross-over experimental
      trial. ANIMALS: Eight healthy, young (3 +/- 1 SD years) adult female alpacas
      weighing 64 +/- 9 SD kg. METHODS: Alpacas were anesthetized with isoflurane by
      mask followed by tracheal intubation and maintenance of anesthesia with
      isoflurane in oxygen and intermittent positive pressure ventilation. Animals were
      assigned to two treatments, butorphanol (0.1 mg kg(-1), IV) and saline (0.01 mL
      kg(-1), IV) in a randomized manner allowing a 2-week interval between treatments.
      Cardiovascular variables included systolic, diastolic, and mean arterial blood
      pressure, heart rate, pulmonary arterial pressure, pulmonary arterial occlusion
      pressure (PAOP), central venous pressure, cardiac output, and pulmonary
      temperature (TEMP). Cardiac index, systemic vascular resistance (SVR), and
      pulmonary vascular resistance (PVR) were calculated. Bispectral index was also
      measured. Arterial and mixed venous blood samples were collected for blood gas
      analysis. All variables were recorded at baseline (time 0) and at 5, 10, 15, 30,
      45 and 60 minutes following injection and were analyzed by using repeated
      measures ANOVA (p < 0.05). PAOP, PVR, and BIS were analyzed by paired t-tests.
      RESULTS: Butorphanol decreased SVR at all times when compared with the baseline,
      but no difference was detected between treatments. TEMP decreased with time in
      both treatments, but they were not different from each other. Other
      cardiovascular, BIS, and blood gas variables were not different between groups.
      CONCLUSION AND CLINICAL RELEVANCE: We conclude that butorphanol had minimal
      effects on the cardiovascular system of the alpacas, causing a mild decrease in
      SVR.

PMID- 17451496
TI  - Nonsteroidal anti-inflammatory drugs in cats: a review.
AB  - OBJECTIVE: To review the evidence regarding the use of nonsteroidal anti
      inflammatory drugs (NSAIDs) in cats. DATABASES USED: PubMed, CAB abstracts.
      CONCLUSIONS: Nonsteroidal anti-inflammatory drugs should be used with caution in
      cats because of their low capacity for hepatic glucuronidation, which is the
      major mechanism of metabolism and excretion for this category of drugs. However,
      the evidence presented supports the short-term use of carprofen, flunixin,
      ketoprofen, meloxicam and tolfenamic acid as analgesics in cats. There were no
      data to support the safe chronic use of NSAIDs in cats.

PMID- 17451497
TI  - Absence of soluble CD14 in saliva of young patients with dental caries.
AB  - It is generally accepted that salivary components are important for dental
      health, but to date no clear correlation has been found between one or more of
      these components and the outcome of dental caries. The identification of salivary
      factors preventing, favoring or signaling dental caries might help to control the
      disease. In the present study, western blotting analysis of whole saliva from 20
      healthy caries-free children showed the presence of the soluble form of CD14, a
      bacterial pattern-recognition receptor for many bacterial components that is
      involved in the innate immune response. The identity of the protein was confirmed
      through N-terminal sequencing by Edman degradation, and by partial sequencing
      with mass spectrometry of tryptic peptides. Conversely, CD14 was completely
      absent in the saliva of 20 age-matched patients affected by two to eight carious
      lesions, but appeared in their saliva a few weeks after dental restoration. These
      results suggest that the absence of salivary soluble CD14 could represent an
      useful index of caries activity, and might be used to detect early carious
      lesions not visible by oral inspection.

PMID- 17451498
TI  - Salivary gland parameters and clinical data related to the underlying disorder in
      patients with persisting xerostomia.
AB  - This study assessed salivary gland parameters and clinical data in patients
      referred to our clinic because of persisting xerostomia of unknown origin, in
      order to facilitate early diagnosis and recognition of the underlying disorder.
      Most patients were referred for diagnostic analysis of a possible Sjogren's
      syndrome (SS). A complete diagnostic work-up was available in all patients (n =
      176), including data on salivary gland function, saliva composition, sialography,
      salivary gland swelling, pattern of complaints, general health, and medication.
      Patients were diagnosed with SS (n = 62), sialosis (n = 45), sodium retention
      syndrome (n = 30), or medication-induced xerostomia (n = 9). In 30 patients no
      disease related to salivary gland pathology was found. Unstimulated whole
      salivary flow was decreased in all patients, except in patients with sodium
      retention syndrome and in patients without salivary gland pathology.
      Submandibular/sublingual salivary flow was lowest in SS patients. SS and sialosis
      patients had increased salivary potassium concentrations, whereas only SS
      patients had increased sodium concentrations. About half of the sialosis patients
      mainly complained of persistent parotid gland swelling. Xerostomia-inducing
      medication was used by most patients. It was concluded that gland-specific
      sialometry and sialochemistry is useful in discriminating between the various
      disorders causing persisting xerostomia.

PMID- 17451499
TI  - Altered fatty acid pattern of phospholipids and triglycerides in the
      submandibular gland of omega3-depleted rats.
AB  - Alteration of the phospholipid (PL) and triglyceride (TG) fatty acid pattern was
      recently documented in several organs of rats depleted in long-chain
      polyunsaturated omega3 fatty acid (omega3 rats). This study extends such a
      knowledge to the submandibular gland. The total PL and TG content of the salivary
      gland was not different in control and omega3 rats. The sole omega3 fatty acids
      found in omega3 rats (C22:5omega3 and C22:6omega3) were present at levels 3-12
      times lower than in control rats. The C22:5omega3/C22:6omega3 ratio was increased
      threefold in omega3 rats. The PL and TG C16:0/C16:1omega7 and C18:0/C18:1omega9
      ratios were decreased in omega3 rats. The conversion of C18:2omega6 to
      C20:4omega6 and C22:4omega6 appeared facilitated in the omega3 rats. Some of
      these rats were injected intravenously, 60-120 min before killing, with either a
      medium-chain triglyceride:fish oil emulsion or a control medium-chain
      triglyceride:olive oil emulsion. The former emulsion increased the PL C22:5omega3
      and C22:6omega3 content and prevented the age-related decrease in
      C16:0/C16:1omega7 and C18:0/C18:1omega9 ratios otherwise also recorded in PL. In
      conclusion, these findings document an increased activity of Delta9-desaturase, a
      more efficient conversion of C18:2omega6 to its metabolites, and an impaired
      generation of C22:6omega3 from C22:5omega3 in omega3 rats.

PMID- 17451500
TI  - Intensity and extent of oral impacts on daily performances by type of self
      perceived oral problems.
AB  - The objectives of this study were to determine the prevalence, intensity, and
      extent of the impacts caused by oral problems, and to compare their intensity and
      extent by the type of oral problem. Four of seven public schools linked to a
      Health Center in Lima, Peru, were randomly selected as clusters, and 805 11-12-yr
      old children participated in the study (response rate: 89.1%). The Spanish (Peru)
      child version of the Oral Impact of Daily Performances (Child-OIDP) was used to
      assess oral impacts. The prevalence of oral impacts was 82.0%. Eating was the
      daily performance most frequently impacted (48.0%). Among children with impacts,
      24.8% reported impacts of severe to very severe intensity, and 73.2% reported
      impacts affecting between one and three daily performances. When the intensity
      and extent of the eight most frequently reported oral problems were compared, a
      statistically significant difference was found only for the extent but not for
      the intensity of the impacts. Oral impacts on daily performances were very common
      and relatively severe among the participating Peruvian children. The pattern of
      the impacts differed according to the type of self-perceived oral problem.
      However, the differences were reflected in the extent, but not in the intensity,
      of the impacts.

PMID- 17451501
TI  - Skeletal bone mineral density in relation to thickness, bone mass, and structure
      of the mandibular alveolar process in dentate men and women.
AB  - Peri-apical radiographs have been used to identify women with low bone mineral
      density (BMD) in various parts of the skeleton, but their usefulness for men has
      not been elucidated. The aim of this study was to test if the mandibular bone
      structure and bone mass in men and women were related to the BMD of the forearms,
      determined by dual X-ray absorptiometry, in 42 men and 42 women (aged 18-84 yr).
      Mandibular alveolar thickness was measured in casts, and alveolar 'bone mass' was
      estimated on digital radiographs using gray-shade distribution. Alveolar bone
      structure was evaluated visually (trabecular pattern) on analog radiographs and
      with its bone texture on digitized radiographs. Bone texture was correlated to
      BMD in both men and women. BMD was correlated to alveolar bone mass and
      trabecular pattern in women, but not in men. Bone texture and body mass index
      (BMI) explained 57% of the variance in BMD for men, whereas trabecular pattern
      and age explained 50% of the variance in BMD for women. Sparse trabeculation was
      associated with osteopenia. We conclude that alveolar bone texture and BMI are
      predictors of BMD for men, and age and trabecular pattern are predictors of BMD
      for women.

PMID- 17451502
TI  - Histomorphometric study on the effects of age on orthodontic tooth movement and
      alveolar bone turnover in rats.
AB  - The aim of this study was to investigate, in a rat model, the effects of age on
      the amount of tooth movement and concomitant changes in alveolar bone turnover
      activity adjacent to orthodontically treated tooth roots. Rats (n = 48) of four
      different age groups (10, 30, 50, and 80 wk of age) were used in the experiment.
      Maxillary first molars were tipped mesially with a nickel titanium alloy coil
      spring for 2 wk by a continuous force of 10 cN. Forty-eight age-matched untreated
      rats were used as controls. The changes in alveolar bone turnover were assessed
      histomorphometrically. Two weeks after the start of tooth movement, the amount of
      tooth movement was found to decrease with age and was significantly different
      among the four age groups. The histomorphometric study demonstrated that, in all
      experimental groups, turnover of alveolar bone increased significantly compared
      with that of each age-matched untreated group. However, the rate of increase
      decreased in an age-related manner. These results suggest that the age-dependent
      decrease in alveolar bone turnover activity, in response to mechanical forces,
      may negatively affect the amount of tooth movement.

PMID- 17451503
TI  - Inhibition of tooth movement by osteoprotegerin vs. pamidronate under conditions
      of constant orthodontic force.
AB  - The undesired movement of anchor teeth, and relapse of previously moved teeth,
      are major clinical problems in orthodontics. Dental implants are increasingly
      used to preserve anchorage, but these are costly and require invasive surgical
      procedures. An alternative strategy for maintaining anchorage may be the use of
      biological inhibitors of osteoclastic bone resorption. In the present study, we
      investigated the relative efficacy of pamidronate vs. osteoprotegerin (OPG) in
      inhibiting bone resorption and tooth movement, using a new orthodontic model in
      mice in which maxillary molars are moved for prolonged periods by near-constant,
      clinically relevant forces. Osteoclast influx to compression sites was initiated
      on day 3, was maximal on day 4, and persisted until at least day 12 after force
      application. Tooth movement paralleled osteoclast numbers. Minimal osteoclast
      apoptosis was observed, suggesting that recruitment, rather than programmed cell
      death, is a critical regulatory mechanism under conditions of constant force.
      Osteoclasts were reduced at compression sites by both OPG (95%) and pamidronate
      (70%); tooth movement was more dramatically inhibited by OPG (77% vs. 34%). Our
      findings indicate that constant orthodontic force regulates the recruitment,
      activation, and viability of osteoclasts, and that OPG could have clinical
      utility in preventing undesired tooth movement.

PMID- 17451504
TI  - Dental fluorosis and dental caries among 12-yr-old children from high- and low
      fluoride areas in Lithuania.
AB  - We investigated the prevalence and severity of dental fluorosis, and the
      occurrence of dental caries, among 12-yr-old children from high- and low-fluoride
      areas in a country with high caries figures and a developing oral healthcare
      system. The sample included a total of 600 lifetime residents from high-fluoride
      (HF; 1.7-2.2 ppm) and low-fluoride (LF; 0.2 ppm) areas in Lithuania. The
      diagnoses of dental fluorosis followed the Thylstrup-Fejerskov Index (TF), and a
      diagnosis of dental caries followed the World Health Organization criteria. In
      the HF area, 66% of the 12-yr-old children had dental fluorosis (TF score > 0)
      compared with 4% in the LF area. The maximum TF severity scores were 7 and 3,
      respectively. The mean number of teeth with fluorosis was 4.5 [95% confidence
      interval (CI) = 4.0, 5.0] for the HF group and 0.2 (95% CI = 0.1, 0.2) for the LF
      group. In the HF group, 72% had a decayed, missing or filled teeth (DMFT) score
      of > 0, compared with 87% in the LF group. The mean DMFT was 2.0 (95% CI = 1.8,
      2.3) in the HF group and 3.5 (95% CI = 3.2, 3.8) in the LF group. Current
      untreated caries (DT) occurred (DT >0) in half of both the HF and LF groups.
      Regardless of the concentration of fluoride in the drinking water, the prevalence
      of past (DMFT > 0) and present (DT > 0) caries was high, calling for more
      emphasis on the prevention of tooth decay in countries, such as Lithuania, with
      high caries figures and a developing oral healthcare system.

PMID- 17451505
TI  - Effects of a new titanium fluoride derivative on enamel de- and remineralization.
AB  - The potential of a new titanium fluoride (TiF) derivative for caries prevention
      was tested in a pH-cycling model. Daily treatments with various concentrations
      (100, 250, and 500 p.p.m.) of TiF were compared with similar sodium fluoride
      (NaF) treatments given at the same pH. Bovine enamel lesions were subjected to 3
      wk of pH cycling. The effects were assessed by analyzing calcium uptake and loss
      in the re- and demineralizing solutions, respectively, and by post pH cycling
      microradiographic analysis of the lesions. Treatments with NaF reduced calcium
      loss, enhanced calcium uptake, and induced overall lesion remineralization.
      Treatments with TiF derivative gradually caused almost complete inhibition of
      calcium loss and uptake (lesion 'arrestment'), irrespective of the concentration
      of the TiF derivative. To test the permanence of protection, sound enamel was
      pretreated with either TiF derivative or NaF, and demineralized for 14 d at pH
      4.4 and 4.6. Calcium loss data show that up to 80% inhibition of demineralization
      could be achieved for the TiF derivative, which was not possible for NaF
      treatments. This inhibition was obtained through a combination of concentration
      and number of treatments. The TiF derivative is a promising agent for the
      prevention of dental caries, especially when aimed at preventing the onset of
      caries.

PMID- 17451506
TI  - Plaque formation and lactic acid production after the use of amine
      fluoride/stannous fluoride mouthrinse.
AB  - The aim of this study was to determine the effects of 3 wk of daily rinsing with
      amine fluoride/stannous fluoride (AmF/SnF(2)) mouthrinse on plaque formation at
      buccal and interproximal sites, and on the acid production in plaque, in a
      randomized clinical trial with 30 participants. The amount of plaque was scored
      according to Turesky's modification of the Quigley and Hein index. Plaque samples
      were collected, before and after sucrose rinsing, from the buccal and
      interproximal surfaces of upper (pre)molars at two baseline visits and on days 2
      and 7 after the discontinuation of 3 wk of daily rinsing. Metabolic acid ions
      were determined by capillary electrophoresis. The results at baseline showed
      higher lactic acid concentrations in resting interproximal plaque than in buccal
      plaque, and a higher acid production in response to sucrose challenge in buccal
      plaque than in interproximal plaque. After 3 wk of use of the AmF/SnF(2)
      mouthrinse, no significant differences in plaque scores were observed, and the
      alleged reduction in acidogenicity of dental plaque was not significant on the
      second day after the last mouthrinse. We conclude that 3 wk of use of AmF/SnF(2)
      rinse once daily does not result in a reduction of plaque formation or in a
      reduction of sucrose metabolism in buccal and interproximal plaque after
      discontinuing the rinse.

PMID- 17451507
TI  - The amyloid protein APin is highly expressed during enamel mineralization and
      maturation in rat incisors.
AB  - This study investigated the expression and localization of APin (which was
      previously identified and cloned from a rat odontoblast cDNA library), during
      ameloblast differentiation in rat incisors, by using in situ hybridization and
      immunohistochemistry. The subcellular localization of APin varied during
      ameloblast differentiation, but was stage-specific. APin mRNA was not expressed
      in pre-ameloblasts, was weakly expressed in secretory ameloblasts, and was
      strongly expressed in maturation-stage ameloblasts as well as in the junctional
      epithelium attached to the enamel of erupted molars. In the maturation-stage
      ameloblasts, APin protein was conspicuous in the supranuclear area (Golgi
      complex) of smooth-ended ameloblasts as well as in both the supranuclear area and
      the ruffle end of ruffle-ended ameloblasts. During ameloblast-lineage cell
      culture, APin was expressed at a low level in the early stages of culture, but at
      a high level in the late stage of culture, which was equivalent to the maturation
      stage. APin protein was efficiently secreted from transfected cells in culture.
      Furthermore, its overexpression and inactivation caused an increase and decrease
      in matrix metalloproteinase-20 (MMP-20) and tuftelin expression, respectively.
      These findings indicate a functional role for APin in the mineralization and
      maturation of enamel that is mediated by the expression of MMP-20 and tuftelin.

PMID- 17451508
TI  - Load-bearing capacity of all-ceramic posterior four-unit fixed partial dentures
      with different zirconia frameworks.
AB  - The aim of this in vitro study was to compare the load-bearing capacity of
      posterior four-unit fixed partial dentures (FPDs) produced with two different
      yttria-stabilized polycrystalline tetragonal zirconia (Y-TZP) ceramics, one being
      a presintered material, the other a fully sintered, hot isostatically pressed
      material. Additionally, as a novel approach, the influence of preliminary
      mechanical damage upon the fracture force of an FPD has been investigated. A
      total of 20 frameworks each were milled from presintered zirconia and from fully
      sintered zirconia. Prior to veneering, 10 frameworks of each material were
      'damaged' by a defined saw cut similar to an accidental flaw generated during
      shape cutting. Before fracture testing, all FPDs were subjected to thermal and
      mechanical cycling. Additionally, scanning electron microscopy was used to
      investigate fracture surfaces. Statistical analysis showed that FPDs milled from
      fully sintered zirconia had a significantly higher fracture resistance compared
      with specimens made from presintered material, whereas preliminary damage did not
      have a significant effect. After aging, FPDs made from both materials were
      capable of withstanding occlusal forces reported in the literature. Therefore,
      both types of Y-TZP may be suitable for posterior four-unit all-ceramic FPDs,
      although further prolonged aging experiments and prospective clinical trials are
      required to prove their fitness for clinical use.

PMID- 17451510
TI  - Atypical mycobacterial infection in patients with cystic fibrosis: update on
      clinical microbiology methods.
AB  - While patients with cystic fibrosis (CF) have had dramatic improvement in their
      survival rates, this has been accompanied by the emergence of more virulent
      pathogens such as Pseudomonas aeruginosa and Burkholderia cepacia complex
      organisms. In addition, there has been emergence of organisms of increasing
      clinical significance such as the nontuberculous mycobacterial (NTM). Although TB
      infection in patients with CF is extremely uncommon, there is growing concern
      with regard to atypical Mycobacterium spp, in particular Mycobacterium abscessus.
      Many methods of decontamination of sputum, which have been adapted from TB
      methodologies, are ineffective; as shown by the overgrowth of P. aeruginosa, it
      is essential that decontamination methods are optimized to overcome this.
      Establishing optimal methods of isolation and determining accurate levels of
      prevalence is of importance as, although NTM may be isolated relatively
      infrequently in CF populations, their clinical status in pulmonary disease is now
      beginning to emerge.

PMID- 17451511
TI  - Conjugated linoleic acid conversion by dairy bacteria cultured in MRS broth and
      buffalo milk.
AB  - AIMS: To evaluate strains of Lactobacilli, Bifidobacteria and Streptococci for
      their ability to produce conjugated linoleic acid (CLA) from free linoleic acid
      (LA). METHODS AND RESULTS: Eight dairy bacteria tolerant to LA were grown in MRS
      broth containing LA (200 microg ml(-1)) and CLA was assessed. Seven bacteria were
      able to form CLA after 24 h of incubation, varying percentage conversion between
      17% and 36%. Lactobacillus casei, Lactobacillus rhamnosus, Bifidobacterium
      bifidum and Streptococcus thermophilus showed the highest LA conversion and were
      inoculated into buffalo milk supplemented with different concentration of LA. The
      production of CLA at 200 microg ml(-1) of LA was two- or threefold in milk than
      MRS broth. All evaluated strains were able to produce CLA from high LA levels
      (1000 microg ml(-1)). CONCLUSIONS: The most tolerant strain to LA was Lact.
      casei. Lacttobacillus rhamnosus produced the maximum level of CLA at high LA
      concentrations (800 microg ml(-1)). The selected bacteria may be considered as
      adjunct cultures to be included on dairy fermented products manufacture. Low
      concentration of LA must be added to the medium to enhance CLA formation.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The production of CLA by strains using
      milks from regional farms as medium offer a possible mechanism to enhance this
      beneficial compound in dairy products and those the possibility to develop
      functional foods.

PMID- 17451512
TI  - Screening and purification for novel cytochrome b5 from uncultured environmental
      micro-organisms.
AB  - AIMS: We describe a sequence-based PCR method suitable for the isolation of a
      novel soluble heme-binding domain of cytochrome b(5) (cyt b(5)) gene directly
      from metagenomic DNA is described. METHODS AND RESULTS: Using the degenerate
      primer set, a cyt b(5) gene was isolated directly from metagenomic DNA. Based on
      the sequence-based PCR method, the similar conserved motif of cyt b(5) from
      Rhodopseudomonas palustris strain makes the novel target gene. The gene encoding
      cyt b(5) was cloned and expressed in Escherichia coli BL21 (DE3) using pET
      expression system. The expressed recombinant enzyme was purified by Ni
      nitrilotriacetic acid affinity chromatography and characterized. CONCLUSIONS:
      Sequence-based strategy is an effective method for application of the novel gene
      from metagenomic DNA. SIGNIFICANCE AND IMPACT OF THE STUDY: Investigation of
      novel genes from metagenome, most of the micro-organism species are largely
      untapped, could represent an interesting and useful reservoir for biological
      processes.

PMID- 17451513
TI  - Characterization of Lactococcus garvieae isolated from radish and broccoli
      sprouts that exhibited a KG+ phenotype, lack of virulence and absence of a
      capsule.
AB  - AIMS: To identify Lactococcus garvieae isolates from radish and broccoli sprouts
      and compare them with virulent and less virulent mutant strains obtained from
      yellowtails with regard to KG phenotype, presence of a capsule and virulence
      towards yellowtails and mice. METHODS AND RESULTS: Comparative 16S rRNA gene
      sequence analysis of six isolates obtained from radish and broccoli sprouts
      indicated that they were L. garvieae (similarity >99%). They were compared with
      KG9502, Lg2 and ATCC49156 strains obtained from yellowtails. A less virulent
      mutant strain Lg2-S was obtained by Lg2 subculture. Biochemical characterization
      of the six strains resembled that of KG9502, Lg2, ATCC49156 and Lg2-S, except for
      saccharose and tagatose acidification and the presence of hippuricase. These six
      strains were nonpathogenic towards yellowtails and mice, nonsusceptible to
      bacteriophages and demonstrated heterogeneity on pulsed-field gel electrophoresis
      analysis. Using transmission electron microscopy, a capsule was observed in
      KG9502 and Lg2 but not in ATCC49156 and Lg2-S. CONCLUSIONS: We isolated L.
      garvieae strains that lacked pathogenicity towards yellowtails and mice from
      radish and broccoli sprouts; these were noncapsulated and exhibited KG(+)
      phenotype. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first documentation
      of L. garvieae isolated from terrestrial plants. These isolates exhibited genetic
      diversity; however, they were noncapsulated and nonpathogenic towards yellowtails
      and mice.

PMID- 17451514
TI  - Periodontal disease as reservoir for multi-resistant and hydrolytic
      enterobacterial species.
AB  - AIMS: This investigation aimed to isolate enteric rods from subgingival sites of
      patients presenting chronic periodontitis lesions, and to assess antimicrobial
      resistance and expression of hydrolytic enzymes. METHODS AND RESULTS:
      Enterobacteriaceae were isolated from 20% patients, and assayed for antimicrobial
      susceptibility and hydrolytic enzymes with specificity to different substrates.
      Isolates comprised seven Enterobacter cloacae (43.75%), five Serratia marcescens
      (31.25%), one Klebsiella pneumoniae (6.25%), one Enterobacter aerogenes (6.25%),
      one Pantoea agglomerans (6.25%), and one Citrobacter freundii (6.25%). Gelatinase
      activity was observed for 75% strains; caseinase and elastase was produced by six
      and two strains, respectively. DNase, lecithinase and lipase were expressed by S.
      marcescens. Most of strains were resistant to ampicillin (93.75%) and
      amoxicillin/clavulanic acid (81.25%). The majority of strains were susceptible to
      cephalosporins and aztreonam. Enterobacteria remained susceptible to imipenem,
      streptomycin and fluoroquinolones. Resistance to gentamicin, amikacin,
      sulfamethoxazole/thrimethoprim, tetracycline, and chloramphenicol were also
      observed. Eight strains presented multiple drug resistance. CONCLUSIONS:
      Subgingival sites from periodontal diseases contain multi-resistant and
      hydrolytic enzyme-producing enterobacteria that may contribute to overall tissue
      destruction and spreading. SIGNIFICANCE AND IMPACT OF THE STUDY: Enterobacteria
      isolated from patients generally considered as healthy individuals poses
      periodontal diseases as reservoir for systemic infections particularly in
      immunocompromised and hospitalized hosts.

PMID- 17451515
TI  - The survival of three strains of Arcobacter butzleri in the presence of lemon,
      orange and bergamot essential oils and their components in vitro and on food.
AB  - AIMS: To test the effect of oils and vapours of lemon, sweet orange and bergamot
      and their components against three Arcobacter butzleri strains. METHODS AND
      RESULTS: The disc diffusion method was used to screen the oils and vapours
      against three strains of A. butzleri. In vitro bergamot was the most inhibitory
      essential oil (EO) and both citral and linalool were effective. On cabbage leaf,
      the water isolate was the least susceptible to bergamot EO, citral and linalool
      (1-2 log reduction), with the chicken isolate being the most susceptible (6-8 log
      reduction). However, the latter appeared not to be susceptible to vapours over 24
      h although type strain and water isolate populations reduced by 8 logs. On
      chicken skin, the effectiveness of the oils was reduced compared with that on
      cabbage leaf. CONCLUSIONS: Bergamot was the most effective of the oils tested and
      linalool the most effective component. All strains tested were less susceptible
      in food systems than in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: Arcobacter
      isolates vary in their response to EO suggesting that the results of type strain
      studies should be interpreted with caution. Bergamot EO has the potential for the
      inhibition of this 'emerging' pathogen.

PMID- 17451516
TI  - Effect of starch- and lipid-based encapsulation on the culturability of two
      Bifidobacterium longum strains.
AB  - AIMS: To assess the applicability of starch- and lipid-based encapsulation
      methods for improving the viability and culturability of two Bifidobacterium
      longum strains stored in fermented and nonfermented foods. MATERIALS AND RESULTS:
      Cells were encapsulated with partially hydrolysed potato starch granules combined
      with amylose coating, or entrapped in cocoa butter matrix. The tested B. longum
      strains were not adherent to the starch granules, and the culturability of the
      cells stored in fermented and nonfermented foods was not improved by starch-based
      encapsulation. Encapsulation of the cells in cocoa butter was found to increase
      the plate counts during storage. In addition to plate counts, viability of the
      cells was measured by fluorescent microscopy using LIVE/DEAD BacLight viability
      assay. Microscopic counts of the viable cells did not change significantly during
      storage, suggesting that the cells remained alive despite becoming unable to grow
      on nutrient agar plates. CONCLUSIONS: Encapsulation with cocoa butter increased
      the culturability of the cells, but encapsulation with hydrolysed potato starch
      had no effect. Culture-independent viability assay suggested that cells remained
      viable despite being unable to grow on agar plates. SIGNIFICANCE AND THE IMPACT
      OF THE STUDY: This study indicates that encapsulation techniques may be useful in
      improving the culturability of bacteria, but the plate counts may yield
      insufficient data on the actual viability of the cells.

PMID- 17451517
TI  - A novel approach for the identification of bacterial taxa-specific molecular
      markers.
AB  - AIMS: To develop and establish a methodology for an oriented and fast
      identification of species taxa-specific molecular markers useful for the
      identification of micro-organisms. METHODS AND RESULTS: From the complete
      microbial genomes available in Pfam database, taxa-specific protein domains were
      identified which lead to the selection of taxa-specific loci. This strategy was
      used to identify six genetic markers: four specific for Pseudomonas syringae pv.
      tomato, one specific for P. syringae pv. syringae and one specific for P. putida.
      The discriminatory potential of these loci was evaluated by Southern
      hybridization using several pseudomonad species and pathovars, by dot-blot
      hybridization and by multiplex PCR optimized for the simultaneous detection of P.
      putida, P. syringae pv. syringae and P. syringae pv. tomato. Sensitivity assays
      indicated a detection limit of approximately 10 pg of chromosomal DNA template
      needed for each bacterium. CONCLUSIONS: The proposed methodology was efficient on
      the selection of six Pseudomonas-specific markers able to discriminate
      Pseudomonas at the species and pathovar level. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The oriented search of taxa-specific molecular probes described in this
      work, which can be easily extended to other groups of bacteria, will improve the
      accuracy and expedite the identification of micro-organisms by DNA-based
      molecular methods.

PMID- 17451518
TI  - Ecological impact of solar ultraviolet-B (UV-B: 320-290 nm) radiation on
      Corynebacterium aquaticum and Xanthomonas sp. colonization on tea phyllosphere in
      relation to blister blight disease incidence in the field.
AB  - AIMS: To assess the effects of solar UV-B radiation on phyllosphere bacteria of
      tea leaves in relation to blister blight disease in the field. METHODS AND
      RESULTS: The effects of UV-B radiation on the phyllosphere microbiology of tea
      (Camellia sinensis) were studied in contrasting wet and dry seasons at a tropical
      site. Wavelength-selective filters were used to separate the effects of UV-B from
      those of other factors. Bacterial populations were quantified in relation to the
      incidence of blister blight disease. Attenuation of UV-B increased the survival
      of Xanthomonas sp. when populations were not water limited, and increased the
      incidence of blister blight, but had no effect on Corynebacterium aquaticum.
      CONCLUSIONS: The effects of solar UV-B on phyllosphere bacteria were substantial
      but depended on both species and interactions with other environmental variables.
      Xanthomonas sp. was more sensitive to UV-B than C. aquaticum, but this did not
      result in differences in population density under high radiation conditions (dry
      season), but only in the wet season when other factors were not limiting.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The role of UV-B on leaf surface
      microbiology in the tropics is marked but depends on other conditions, and the
      contrasting UV-B responses of different organisms can be masked by other limiting
      factors.

PMID- 17451519
TI  - In vitro development of Cryptosporidium parvum in serum-free media.
AB  - AIM: To compare commercially available serum-free media with common, standard,
      growth medium for their ability to support growth of Cryptosporidium parvum in
      HCT-8 cell cultures. METHODS AND RESULTS: Twelve serum-free media formulations
      with or without additional supplements were tested against a standard growth
      medium containing 2% FBS in HCT-8 cell cultures. After a 48-h incubation period,
      the level of parasite development was determined by ELISA. The extent of
      development in the serum-free media was determined as a percentage of infections
      compared with those obtained using a standard growth medium. CONCLUSIONS: Several
      of the serum-free media formulations, which included MDCK, UltraMDCK, PC-1,
      UltraCHO and UltraCulture, compared favourably with a traditional, standard
      growth medium. Moreover, increasing FBS concentrations to 10% actually resulted
      in an overall decrease in development in many cultures. SIGNIFICANCE AND IMPACT
      OF THE STUDY: Several serum-free medium formulations are available which allow
      development of C. parvumin vitro at levels comparable with standard media
      employing FBS. These serum-free media are particularly useful for applications,
      which may require a more defined medium without the presence of FBS. Moreover,
      the elimination of FBS as a variable allows investigators the ability to more
      closely regulate their experimental systems when growing C. parvum in cell
      cultures.

PMID- 17451520
TI  - Performance of recombinant ESAT-6 antigen (ML0049) for detection of leprosy
      patients.
AB  - AIMS: The study was aimed to evaluate the Mycobacterium leprae recombinant early
      secreted antigenic target-6 (rESAT-6) for its serological performance in leprosy
      patients. METHODS AND RESULTS: Employing enzyme-linked immunosorbent assay
      (ELISA), serum samples were tested for prevalence of immunoglobulin G antibodies
      against M. leprae rESAT-6. The results revealed that the sensitivity of the assay
      for smear-positive leprosy patients was 82.4% (14 of 17) while for smear-negative
      patients it was 19.4% (six of 31). Interestingly, the performance of ESAT-6-based
      assay was statistically comparable with anti-phenolic glycolipid-I antibody
      detecting ELISA, a most widely studied serological assay in leprosy. Regarding
      specificity, none of the 48 controls was positive indicating that antibody
      response to ESAT-6 was highly specific. Moreover, a high concordance between
      bacterial index and anti-ESAT-6 antibody-detecting assay was noted. CONCLUSIONS:
      Recombinant ESAT-6 seems to be a potential serological reagent for detection of
      M. leprae infection. SIGNIFICANCE AND IMPACT OF THE STUDY: ESAT-6 serology may
      have utility for (i) early diagnosis, particularly, of highly infectious form
      (multibacillary, MB) of leprosy, (ii) monitoring the response in smear-positive
      leprosy patients during the course of the chemotherapy, (iii) classification of
      leprosy patients into MB and paucibacillary groups for treatment purpose. Hence,
      further research on these lines is warranted.

PMID- 17451521
TI  - Optimization of culture conditions for production of the anti-tubercular alkaloid
      hirsutellone A by Trichoderma gelatinosum BCC 7579.
AB  - AIMS: This work aimed to optimize the culture conditions for production of a
      novel and potent anti-tubercular alkaloid, hirsutellone A, by the saprophytic
      soil fungus Trichoderma gelatinosum BCC 7579. METHODS AND RESULTS: The fungus was
      initially cultured in shake flasks at 25 degrees C in the potato dextrose broth
      (PDB) supplemented with various carbon and nitrogen sources and mineral salts to
      select suitable medium for mycelial growth and hirsutellone A production.
      Cultivation conditions were further optimized by adjusting initial pH and
      changing temperature levels to maximize the production of hirsutellone A. The
      optimal condition that increased the production of hirsutellone A from 19.04 mg
      l(-1), obtained from basal condition, to 610.55 mg l(-1) and reduced the
      cultivation time from 40 to 6 days was to cultivate in a shaker at 200 rev min(
      1) at 25 degrees C in PDB plus 20 g l(-1) soluble starch, 10 g l(-1) peptone and
      2.5% (v/v) salt solution with initial pH of 7. Production of hirsutellone A in
      larger-scale using a 5-l batch fermenter was also completed yielding 958 mg l(-1)
      of hirsutellone A within 6 days. CONCLUSIONS: The suitable culture conditions for
      hirsutellone A production by T. gelatinosum BCC 7579 was the cultivation in 5-l
      fermenter at 25 degrees C in PDB plus 20 g l(-1) soluble starch, 10 g l(-1)
      peptone and 2.5% (v/v) salt solution with an initial pH of 7. SIGNIFICANCE AND
      IMPACT OF THE STUDY: The production of hirsutellone A in a fermenter to obtain a
      high yield and reduce an incubation period will become very useful in anti
      tubercular drug development process in the future.

PMID- 17451522
TI  - Alcoholic fermentation and its prevention by Lactobacillus buchneri in whole crop
      rice silage.
AB  - AIMS: To evaluate the fermentation characteristics and the effects of
      Lactobacillus buchneri inoculation in ensiling whole crop rice. METHODS AND
      RESULTS: Laboratory-scale silages were prepared from whole crop rice harvested at
      yellow-ripe stage. The crop was ensiled for 2 months with and without inoculation
      of L. buchneri at 10(4), 10(5) and 10(6) CFU g(-1). The effect of prolonged
      ensiling was also studied by using the same crop; the silos were opened at 1, 3,
      6 and 12 months, while the inoculation was made at 10(5) CFU g(-1). Enhanced
      alcoholic fermentation was found in untreated silage; the sum of ethanol and 2,3
      butanediol were seven times higher at 2 months than those of lactic and volatile
      fatty acids, while the differences were diminished at 12 months owing to the
      reduction of ethanol in the late ensiling period. Inoculation of L. buchneri
      inhibited the alcohols; however, ethanol yet prevailed over the fermentation
      until 6 months, after which acetic acid became the main product in the inoculated
      silage. Regardless of inoculation and ensiling period, yeasts were not found in
      whole crop rice silage. CONCLUSIONS: Substantial amounts of ethanol and 2,3
      butanediol would be produced in silage prepared from whole crop rice. The
      alcoholic fermentation can be suppressed when inoculated with L. buchneri.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Inoculation of L. buchneri could be an
      option to prevent ethanol fermentation in silage.

PMID- 17451523
TI  - Influence of pH of TSI medium on the detection of hydrogen sulfide production by
      Campylobacter hyointestinalis.
AB  - AIMS: To examine the influence of pH of triple sugar iron (TSI) agar medium on
      the detection of hydrogen sulfide (H(2)S) production in Campylobacter
      hyointestinalis ssp. hyointestinalis (CHH). METHODS AND RESULTS: TSI medium was
      adjusted by the addition in HCl or NaOH to cover a pH 6.0-9.0. One loopful of
      bacterial growth of CHH strain ATCC 35217 was inoculated into each different pH
      medium, and incubated at 37 degrees C under micro-aerobic conditions. The H(2)S
      production was not detectable even after incubation for 72 h in acidic medium pH;
      however, TSI with alkaline pH (8.0-9.0) allowed detection as early as 3 h of
      incubation. A total of 20 CHH strains from various animal sources were examined
      for the detection of H(2)S production in TSI medium with pH 9.0. The H(2)S was
      detected in all the strains examined within 12 h, and the judgment was
      unambiguous. CONCLUSION: The results showed that the detection of H(2)S
      production by CHH was influenced by medium pH, and TSI with alkaline condition is
      highly sensitive. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of the
      present study suggest that TSI medium with alkaline pH contributes to fast
      detection and led to unambiguous judgment of H(2)S production by CHH.

PMID- 17451524
TI  - Species identification of clinically important Aeromonas spp. by restriction
      fragment length polymorphism of 16S rDNA.
AB  - AIMS: The aim of the study was to characterize 16S rDNA of Aeromonas spp. to
      rapidly identify clinically important species of these bacteria. METHODS AND
      RESULTS: Sequence analysis of published 16S rDNA for unique restriction sites
      revealed prospect of species identification. Extraction of genomic DNA followed
      by amplification and step-by-step restriction endonuclease digestion of 16S rDNA
      was able to identify Aeromonas spp. of medical significance. Validation of the
      method was performed by subjecting 53 Aeromonas strains of multiple origin to
      similar treatment. Results of the study were in agreement with corresponding
      species of the isolates. CONCLUSIONS: The method developed offers an easily
      interpretable tool for the identification of Aeromonas spp. of clinical
      relevance. SIGNIFICANCE AND IMPACT OF THE STUDY: The developed methodology should
      facilitate routine laboratory diagnosis of Aeromonas spp. from clinical cases to
      species level.

PMID- 17451525
TI  - A novel NADH-dependent carbonyl reductase with unusual stereoselectivity for (R)
      specific reduction from an (S)-1-phenyl-1,2-ethanediol-producing micro-organism:
      purification and characterization.
AB  - AIMS: To purify and characterize the (R)-specific carbonyl reductase from Candida
      parapsilosis; to compare the enzyme with other stereospecific oxidoreductases;
      and to develop an available procedure producing optically active (R)-1-phenyl-1,2
      ethanediol (PED). METHODS AND RESULTS: An (R)-specific carbonyl reductase was
      found and purified from C. parapsilosis through four steps, including blue
      sepharose affinity chromatography. The relative molecular mass of the enzyme was
      estimated to be 35 kDa on gel-filtration chromatography and 37.5 kDa on Sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis. The purified enzyme catalysed
      the reduction of various ketones, including alkyl and aromatic ketones, and was
      specific to short-chain and medium-chain alkyl ketones. The enzyme activity was
      inhibited by divalent ion of CuSO(4) and FeSO(4), whereas zincum ion stimulated
      its activity. For catalysing reduction, the enzyme performed maximum activity at
      pH 6.0 and the optimum temperature was 45 degrees C. The carbonyl reductase
      catalysed asymmetric reduction of beta-hydroxyacetophenone to the corresponding
      (R)-PED with the optical purity of 100% enantiomeric excess (e.e.). By analysing
      its partial amino acid sequences, the enzyme was proposed to be a novel
      stereospecific carbonyl reductase. CONCLUSIONS: The purified carbonyl reductase
      showed unusual stereospecificity and catalysed the NADH-dependent reduction of
      beta-hydroxyacetophenone to (R)-PED. The enzyme was different from other
      stereoselective oxidoreductases in catalytic properties. SIGNIFICANCE AND IMPACT
      OF THE STUDY: The discovery of (R)-specific oxidoreductase exhibiting unusual
      stereospecificity towards hydroxyl ketone is valuable for the synthesis of both
      enantiomers of useful chiral alcohols, and provides research basis for the
      achievement of profound knowledge on the relationship between structure and
      catalytic function of (R)-specific enzymes, which is meaningful for the
      alteration of stereospecificity by molecular methods to obtain the enzymes with
      desired stereospecificity.

PMID- 17451526
TI  - Expression of ksdD gene encoding 3-ketosteroid-Delta1-dehydrogenase from
      Arthrobacter simplex in Bacillus subtilis.
AB  - AIMS: To improve KSDH enzyme activity and the transformation level for androst-4
      ene-3,17-dione. METHODS AND RESULTS: 3-ketosteroid-Delta(1)-dehydrogenase gene
      from Arthrobacter simplex was expressed in Bacillus subtilis under the control of
      P43 promoter. The molecular weight of expressed enzyme was about 55 kDa by SDS
      PAGE analysis. The activities of intracellular and extracellular soluble enzymes
      examined by spectrophotometrical method were 110 +/- 0.5 mU mg(-1) and 15 +/- 0.6
      mU mg(-1) of protein, respectively. The transformation rate of androst-4-ene-3,17
      dione was 45.3% in the B. subtilis recombinant cells. CONCLUSIONS: The enzyme
      activity of KSDH expressed in B. subtilis was improved about 30-fold compared
      with that of Arthrobacter simplex, and the transformation level of androst-4-ene
      3,17-dione by the B. subtilis recombinant cells was improved about 10-fold.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The recombinant B. subtilis cells used for
      biotransformation of steroids provide a new method for production of steroid
      medicine. The time required for transformation of B. subtilis is much shorter
      than that of other bacteria, which means it will have wider usage in
      biopharmaceutical industry.

PMID- 17451527
TI  - Recovery of Flavobacterium psychrophilum viable cells using a charcoal-based
      solid medium.
AB  - AIMS: Flavobacterium psychrophilum is the etiological agent of the cold-water
      disease in salmonids. This micro-organism is somewhat fastidious being difficult
      to isolate and culture. The aim of this study was to develop a new solid medium
      which improves the recovery of viable cells from a sample. METHODS AND RESULTS:
      Six different media [nutrient agar (NA), NA + charcoal (NAC), enriched Anacker
      Ordal serum (EAOS), EAOS supplemented with aromatic compounds (EAOSa), EAOS with
      activated charcoal (EAOC) and EAOC supplemented with aromatic compounds (EAOCa)],
      three of them containing activated charcoal, were used to recover isolated
      colonies from a diluted sample of Fl. psychrophilum THC02-90. Pair wise
      comparisons between different media were carried out using the test of bootstrap
      to determine the best solid medium and if the presence of activated charcoal
      increased the number of colonies. The results showed that activated charcoal
      improved the recovery of viable cells in all the cases and NAC was slightly
      better than EAOCa but more variable. CONCLUSIONS: Activated charcoal has a great
      capacity of absorption of toxic compounds and it has no nutritional value, so the
      problems to culture and isolate Fl. psychrophilum are in part due to an
      inhibition phenomenon. The use of EAOCa can overcome some of these problems.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The improvement in Fl. psychrophilum
      cultivation will facilitate physiological, biochemical and genetic studies with
      this bacterium.

PMID- 17451528
TI  - Characterization of neuronal subsets surrounded by perineuronal nets in the
      rhesus auditory brainstem.
AB  - The distribution of perineuronal nets and the potassium channel subunit Kv3.1b
      was studied in the subdivisions of the cochlear nucleus, the medial nucleus of
      the trapezoid body, the medial and lateral superior olivary nuclei, the lateral
      lemniscal nucleus and the inferior colliculus of the rhesus monkey. Additional
      sections were used for receptor autoradiography to visualize the patterns of
      GABAA and GABAB receptor distribution. The Kv3.1b protein and perineuronal nets
      [visualized as Wisteria floribunda agglutinin (WFA) binding] were revealed,
      showing corresponding region-specific patterns of distribution. There was a
      gradient of labelled perineuronal nets which corresponded to that seen for the
      intensity of Kv3.1b expression. In the cochlear nucleus intensely and faintly
      stained perineuronal nets were intermingled, whereas in the medial nucleus of the
      trapezoid body the pattern changed to intensely stained perineuronal nets in the
      medial part and weakly labelled nets in its lateral part. In the inferior
      colliculus, intensely labelled perineuronal nets were arranged in clusters and
      faintly labelled nets were arranged in sheets. Using receptor autoradiography,
      GABAB receptor expression in the anterior ventral cochlear nucleus was revealed.
      The medial part of the medial nucleus of the trapezoid body showed a high number
      of GABAA binding sites whereas the lateral part exhibited more binding sites for
      GABAB. In the inferior colliculus, we found moderate GABAB receptor expression.
      In conclusion, intensely WFA-labelled structures are those known to be
      functionally involved in high-frequency processing.

PMID- 17451529
TI  - Morphometrics and inertial properties in the body segments of chimpanzees (Pan
      troglodytes).
AB  - Inertial characteristics and dimensions of the body and body segments form an
      integral part of a biomechanical analysis of motion. In primate studies, however,
      segment inertial parameters of non-human hominoids are scarce and often obtained
      using varying techniques. Therefore, the principal aim of this study was to
      expand the existing chimpanzee inertial property data set using a non-invasive
      measuring technique. We also considered age- and sex-related differences within
      our sample. By means of a geometric model based on Crompton et al. (1996; Am J
      Phys Anthropol 99, 547-570) we generated inertial properties using external
      segment length and diameter measurements of 53 anaesthetized chimpanzees (Pan
      troglodytes). We report absolute inertial parameters for immature and mature
      subjects and for males and females separately. Proportional data were computed to
      allow the comparison between age classes and sex classes. In addition, we
      calculated whole limb inertial properties and we discuss their potential
      biomechanical consequences. We found no significant differences between the age
      classes in the proportional data except for hand and foot measures where
      juveniles exhibit relatively longer and heavier distal segments than adults.
      Furthermore, most sex-related differences can be directly attributed to the
      higher absolute segment masses in male chimpanzees resulting in higher moments of
      inertia. Additionally, males tend to have longer upper limbs than females.
      However, regarding proportional data we discuss the general inertial properties
      of the chimpanzee. The described segment inertial parameters of males and
      females, and of the two age classes, represent a valuable data set ready for use
      in a range of biomechanical locomotor models. These models offer great potential
      for improving our understanding of early hominin locomotor patterns.

PMID- 17451530
TI  - HSP110, caspase-3 and -9 expression in physiological apoptosis and apoptosis
      induced by in vivo embryonic exposition to all-trans retinoic acid or irradiation
      during early mouse eye development.
AB  - Apoptosis is an essential physiological process in embryonic development. In the
      developing eye of vertebrates, three periods of developmental apoptosis can be
      distinguished: early, intermediate and later. Within the apoptosis pathway,
      caspases play a crucial role. It has also been shown that HSP110 may have a
      potential role in apoptosis. The aim of this research was to study the expression
      of HSP110, caspase-3 and -9 in physiological, retinoic- or irradiation-induced
      apoptosis during early eye development. Seven pregnant C57Bl/6J mice received 80
      mg kg(-1) of all-trans retinoic acid mixed with sesame oil. Seven pregnant NMRI
      mice received 2 Gy irradiation at the same gestational day. Control mice of both
      strains (seven mice of each) were not submitted to any treatment. Embryos were
      harvested at 3, 6, 12 and 24 h after exposition, fixed, dehydrated and embedded.
      Coronal sections (5 microm) were made. Slide staining occurred alternatively
      using anti-caspase-3, anti-caspase-9 and anti-HSP110 immunohistochemistry. HSP110
      and caspase-3 expression presented similar topographic and chronological
      patterns, whereas expression of HSP110 was more precocious in retinoic acid
      treated embryos. After retinoic exposure, caspase-3- and HSP110-positive cells
      were increased in the region of the optic vesicle. By contrast, after
      irradiation, caspase-3- and HSP110-positive cells were noticeably increased in
      the optic vesicle, peri-optical mesoderm but less in lens placode. HSP110 was
      expressed before caspase-3. By contrast, caspase-9 was expressed by a very small
      number of cells in the optic vesicle either under physiological or under
      teratogenic conditions. Thus, it seems that activation of caspase-9 is
      dispensable in early eye developmental apoptosis.

PMID- 17451531
TI  - Skeletogenesis in the swell shark Cephaloscyllium ventriosum.
AB  - Extant chondrichthyans possess a predominantly cartilaginous skeleton, even
      though primitive chondrichthyans produced bone. To gain insights into this
      peculiar skeletal evolution, and in particular to evaluate the extent to which
      chondrichthyan skeletogenesis retains features of an osteogenic programme, we
      performed a histological, histochemical and immunohistochemical analysis of the
      entire embryonic skeleton during development of the swell shark Cephaloscyllium
      ventriosum. Specifically, we compared staining properties among various
      mineralizing tissues, including neural arches of the vertebrae, dermal tissues
      supporting oral denticles and Meckel's cartilage of the lower jaw. Patterns of
      mineralization were predicted by spatially restricted alkaline phosphatase
      activity earlier in development. Regarding evidence for an osteogenic programme
      in extant sharks, a mineralized tissue in the perichondrium of C. ventriosum
      neural arches, and to a lesser extent a tissue supporting the oral denticle,
      displayed numerous properties of bone. Although we uncovered many differences
      between tissues in Meckel's cartilage and neural arches of C. ventriosum, both
      elements impart distinct tissue characteristics to the perichondral region.
      Considering the evolution of osteogenic processes, shark skeletogenesis may
      illuminate the transition from perichondrium to periosteum, which is a major bone
      forming tissue during the process of endochondral ossification.

PMID- 17451532
TI  - Human TRP14 gene homologue from amphioxus Branchiostoma belcheri: identification,
      evolution, expression and functional characterization.
AB  - Thioredoxin-related protein of 14 kDa, TRP14, has previously been identified only
      in humans. Here we report the identification and expression of an amphioxus TRP14
      gene, named AmphiTRP14, the first such data in a non-mammalian organism.
      AmphiTRP14 consists of a 372-bp open reading frame coding for a 123-amino-acid
      protein with a calculated molecular weight of 14 kDa. It shares 56% identity with
      human TRP14 and possesses a highly conserved motif CPDC. Sequence comparison
      suggests the evolutionary appearance of the four-exon-three-intron organization
      of TRP14 genes after the split of protostome/deuterostome, which is highly
      conserved since then. AmphiTRP14 has been successfully expressed in Escherichia
      coli and purified. The recombinant protein exhibited features characteristic of
      human TRP14, including a reductase activity towards insulin. Both in situ
      hybridization histochemistry and immunohistochemistry revealed that AmphiTRP14
      was expressed in a tissue-specific manner, with the most abundant expression in
      the hepatic caecum, ovary and hind-gut. This suggests that AmphiTRP14 plays a
      fundamental but tissue-specific role, or alternatively reflects differences in
      the tissue susceptibility to oxidative damage.

PMID- 17451533
TI  - Effect of toe and heel elevation on calculated tendon strains in the horse and
      the influence of the proximal interphalangeal joint.
AB  - The sagittal alteration of hoof balance is a common intervention in horses, with
      corrective shoeing being one of the most frequently applied methods of managing
      tendonitis. However, the effect of toe or heel elevation on tendon strains is
      poorly understood. This study aimed to examine the effect of toe and heel wedges
      on the superficial digital flexor tendon, deep digital flexor tendon, and the
      third interosseous muscle or suspensory ligament strains using in vivo data and
      an accurate subject-specific model. Kinematic data were recorded using invasive
      markers at the walk and trot. Computerized tomography was then used to create a
      subject-specific model of an equine distal forelimb and strains were calculated
      for the superficial digital flexor tendon, the deep digital flexor tendon
      accessory ligament and the suspensory ligament for seven trials each of normal
      shoes, and toe and heel elevation. As the proximal interphalangeal joint is often
      ignored in strain calculations, its influence on the strain calculations was also
      tested. The deep ligament showed the same results for walk and trot with the heel
      wedge decreasing peak strain and the toe wedge increasing it. The opposite
      results were seen in the suspensory ligament and the superficial digital flexor
      tendon with the heel wedge increasing peak strain and the toe wedge decreasing
      it. The proximal interphalangeal joint was shown to be influential on the strains
      calculated with normal shoes and the calculated effect of the wedges. Our results
      imply that corrective shoeing appears to decrease strain in the tendon being
      targeted; the possibility of increases in strain in other structures should also
      be considered.

PMID- 17451535
TI  - Curcuma longa extract as a histological dye for collagen fibres and red blood
      cells.
AB  - Crude ethanolic extract and column chromatographic fractions of the Allepey
      cultivar of Curcuma longa Roxb, commonly called turmeric (tumeric) in commerce,
      were used as a stain for tissue sections. Staining was carried out under basic,
      acidic and neutral media conditions. Inorganic and organic dissolution solvents
      were used. The stain was used as a counterstain after alum and iron
      haematoxylins. C. longa stained collagen fibres, cytoplasm, red blood cells and
      muscle cells yellow. It also stained in a fashion similar to eosin, except for
      its intense yellow colour. Preliminary phytochemical evaluation of the active
      column fraction revealed that it contained flavonoids, free anthraquinone and
      deoxy sugar. A cheap, natural dye can thus be obtained from C. longa.

PMID- 17451534
TI  - Human mesenchymal stem cells at the single-cell level: simultaneous seven-colour
      immunofluorescence.
AB  - Extracellular, intracellular or surface proteins can be used as putative markers
      to characterize human mesenchymal stem cells (hMSC). However, these markers are
      also expressed by other cell types and primary cell pools reveal considerable
      heterogeneity. Therefore, the simultaneous detection of several markers on a
      single cell appears to be an attractive approach to identify hMSC. Here we
      demonstrate the specific distinction of human MSC from human osteoblasts via
      seven-colour fluorescence on the single cell level with simultaneous marker
      detection of CD44, CD105/endoglin, CD106/VCAM-1, collagen-IV, fibronectin, actin
      and DAPI nuclear staining. We performed spectral image acquisition using a Sagnac
      type interferometer. Subsequent linear unmixing allowed for decomposition of each
      pixel in its spectral components. Our approach reveals a typical expression
      profile of the adherent singular cells, allowing the specific distinction between
      hMSC and osteoblasts on the single cell level.

PMID- 17451538
TI  - Decrease in the number and apoptosis of alveolar bone osteoclasts in estrogen
      treated rats.
AB  - BACKGROUND AND OBJECTIVE: Bone is a mineralized tissue that is under the
      influence of several systemic, local and environmental factors. Among systemic
      factors, estrogen is a hormone well known for its inhibitory function on bone
      resorption. As alveolar bone of young rats undergoes continuous and intense
      remodeling to accommodate the growing and erupting tooth, it is a suitable in
      vivo model for using to study the possible action of estrogen on bone. Thus, in
      an attempt to investigate the possibility that estrogen may induce the death of
      osteoclasts, we examined the alveolar bone of estrogen-treated rats. MATERIAL AND
      METHODS: Fifteen, 22-d-old female rats were divided into estrogen, sham and
      control groups. The estrogen group received estrogen and the sham group received
      corn oil used as the dilution vehicle. After 8 d, fragments containing alveolar
      bone were removed and processed for light microscopy and transmission electron
      microscopy. Sections were stained with hematoxylin and eosin and tartrate
      resistant acid phosphatase (TRAP)-an osteoclast marker. Quantitative analysis of
      the number of TRAP-positive osteoclasts per mm of bone surface was carried out.
      For detecting apoptosis, sections were analyzed by the Terminal deoxynucleotidyl
      transferase-mediated dUTP Nick-End Labeling (TUNEL) method; TUNEL/TRAP combined
      methods were also used. RESULTS: The number of TRAP-positive osteoclasts per mm
      of bone surface was significantly reduced in the estrogen group compared with the
      sham and control groups. TRAP-positive osteoclasts exhibiting TUNEL-positive
      nuclei were observed only in the estrogen group. In addition, in the estrogen
      group the ultrastructural images revealed shrunken osteoclasts exhibiting nuclei
      with conspicuous and tortuous masses of condensed chromatin, typical of
      apoptosis. CONCLUSION: Our results reinforce the idea that estrogen inhibits bone
      resorption by promoting a reduction in the number of osteoclasts, thus indicating
      that this reduction may be, at least in part, a consequence of osteoclast
      apoptosis.

PMID- 17451539
TI  - Differential platelet-activating factor synthesis by monocytes and
      polymorphonuclear leukocytes from subjects with localized aggressive
      periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Platelet-activating factor is elevated in localized
      aggressive periodontitis. We previously demonstrated that the elevated level of
      platelet-activating factor in localized aggressive periodontitis is at least
      partially attributable to low levels of platelet-activating factor
      acetylhydrolase, the enzyme that catabolizes platelet-activating factor. The
      objective of this study was to determine if platelet-activating factor synthesis
      was also elevated in localized aggressive periodontitis. To test this, platelet
      activating factor synthesis was quantified in the monocytes and polymorphonuclear
      neutrophils of periodontally healthy patients and of subjects with localized
      aggressive periodontitis. MATERIAL AND METHODS: Cells were labeled with
      [(3)H]acetate and treated with vehicle or stimulated with calcium ionophore
      A23187. Platelet-activating factor was extracted and quantified by scintillation
      counting. RESULTS: For both subject groups, resting monocytes and
      polymorphonuclear neutrophils produced platelet-activating factor, and calcium
      ionophore A23187 stimulated platelet-activating factor production in both cell
      types. However, calcium ionophore A23187-activated monocytes from subjects with
      localized aggressive periodontitis produced less platelet-activating factor than
      did activated periodontally healthy monocytes (p < 0.0001), suggesting an
      aberrant calcium ionophore A23187 response in monocytes from subjects with
      localized aggressive periodontitis. Indeed, when the data were expressed as fold
      induction of platelet-activating factor synthesis in response to calcium
      ionophore A23187, monocytes from subjects with localized aggressive periodontitis
      exhibited only a fourfold increase in platelet-activating factor synthesis,
      whereas calcium ionophore A23187-stimulated monocytes from periodontally healthy,
      chronic periodontitis and generalized aggressive periodontitis subjects produced
      approximately 12 times more platelet-activating factor than did resting
      monocytes. In contrast, both resting and activated localized aggressive
      periodontitis polymorphonuclear neutrophils synthesized more platelet-activating
      factor than did periodontally healthy polymorphonuclear neutrophils. CONCLUSION:
      These data suggest that high levels of platelet-activating factor in subjects
      with localized aggressive periodontitis result from both increased synthesis and
      reduced catabolism. While localized aggressive periodontitis polymorphonuclear
      neutrophils contribute to increased platelet-activating factor mass through
      synthesis, the contribution of monocytes is probably the result of reduced
      catabolism by platelet-activating factor acetylhydrolase.

PMID- 17451540
TI  - (-)-Epigallocatechin gallate induces apoptosis, via caspase activation, in
      osteoclasts differentiated from RAW 264.7 cells.
AB  - BACKGROUND AND OBJECTIVE: Alveolar bone resorption is a characteristic feature of
      periodontal diseases and involves removal of both the mineral and the organic
      constituents of the bone matrix, a process mainly carried out by multinucleated
      osteoclast cells. (-)-Epigallocatechin gallate, the main constituent of green tea
      polyphenols, has been reported to induce the apoptotic cell death of osteoclasts
      and to modulate caspase activation in various tumor cells. In the present study,
      we investigated the inhibitory effect of (-)-epigallocatechin gallate on
      osteoclast survival and examined if (-)-epigallocatechin gallate mediates
      osteoclast apoptosis via caspase activation. MATERIAL AND METHODS: The effect of
      (-)-epigallocatechin gallate on osteoclast survival was examined by tartrate
      resistant acid phosphatase (TRAP) staining in osteoclasts differentiated from RAW
      264.7 cells. In addition, we evaluated the apoptosis of osteoclasts by (-)
      epigallocatechin gallate using a DNA-fragmentation assay. Involvement of caspase
      in (-)-epigallocatechin gallate-mediated osteoclast apoptosis was evaluated by
      treatment with a general caspase inhibitor, Z-VAD-FMK. Moreover, the effect of (
      )-epigallocatechin gallate on the activation of caspase-3 was assessed by a
      colorimetric activity assay and western blotting. RESULTS: (-)-Epigallocatechin
      gallate significantly inhibited, in a dose-dependent manner, the survival of
      osteoclasts differentiated from RAW 264.7 cells and induced the apoptosis of
      osteoclasts. Treatment with (-)-epigallocatechin gallate resulted in DNA
      fragmentation and induced the activation of caspase-3 in RAW 264.7 cell-derived
      osteoclasts. Additional treatment with Z-VAD-FMK suppressed these effects of (-)
      epigallocatechin gallate. CONCLUSION: From these findings, we could suggest that
      (-)-epigallocatechin gallate might prevent alveolar bone resorption by inhibiting
      osteoclast survival through the caspase-mediated apoptosis.

PMID- 17451541
TI  - Epidemiology of periodontal status in dentate adults in France, 2002-2003.
AB  - BACKGROUND AND OBJECTIVE: Few recent nationwide studies of the periodontal
      landscape in European countries have been developed from the point of view of
      attachment loss and pocket depth. Decision makers are not always in a position to
      estimate the burden of periodontal disease. The purpose of this study was to
      investigate the prevalence and the oral distribution of periodontal status among
      dentate adults in the general population of France. MATERIAL AND METHODS: In 2002
      2003, a National Periodontal and Systemic Examination Survey was organized to a
      stratified quota sample of 2144 adults, aged 35-64 years, nationwide.
      Participants with six or more teeth were selected from the Health Examination
      Centers of the National Health Insurance. Measurement of periodontal health was
      assessed by clinical attachment level and probing depth. RESULTS: A total of
      95.40% and 82.23% of adults were found to have clinical attachment loss and
      periodontal pockets, respectively. Population prevalence estimates indicated that
      loss of attachment > or = 5 mm is 46.68% and probing depth (> 5 mm) is 10.21%.
      However, clinical attachment loss of > or = 5 mm occurred in only 0.88 sites in
      an individual. Periodontal depth pocket generalized forms were as follows: 78%
      slight, 18% moderate and 4% severe. Multiple logistic regression analyses showed
      significant differences of attachment loss values between types of tooth (molar,
      incisors, canines, or premolars). CONCLUSION: Based on the International
      Classification of Periodontal Diseases, approximately 50% of adults in France may
      suffer from a severe attachment loss problem. Periodontal pockets are an uncommon
      condition in France. Significant differences in the prevalence of loss of
      attachment and probing depth with respect to location of attack have implications
      in the purchase and development of screening and treatment services.

PMID- 17451542
TI  - Nicotine increases the collagen-degrading ability of human gingival fibroblasts.
AB  - BACKGROUND AND OBJECTIVE: The objective of this study was to determine the
      effects that nicotine and the combination of nicotine and Porphyromonas
      gingivalis supernatant have on human gingival fibroblast-mediated collagen
      degradation. MATERIAL AND METHODS: Human gingival fibroblasts were cultured with
      25-500 microg/ml of nicotine in collagen-coated six-well plates. On days 1-5, the
      conditioned media was collected for zymography and western blot analyses of
      matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases
      (TIMPs). The cells were then removed and the collagen cleavage visualized by
      Coomassie blue staining. To examine the combined effect, 250 microg/ml of
      nicotine and 10% v/v culture supernatant of P. gingivalis ATCC 33277 were added
      to the human gingival fibroblasts. The mRNA levels of multiple MMPs and TIMPs
      were monitored. RESULTS: Nicotine increased the human gingival fibroblast
      mediated collagen cleavage. The MMP-14 and MMP-2 produced by the nicotine-treated
      human gingival fibroblasts more readily underwent zymogen activation. Nicotine
      treatment resulted in TIMP-2 redistribution to the cell surface. The mRNAs of
      multiple MMPs and TIMPs were unaltered by nicotine. An additive collagen cleavage
      effect was observed when the human gingival fibroblasts were treated with both
      nicotine and P. gingivalis. CONCLUSION: Nicotine increased human gingival
      fibroblast-mediated collagen degradation, in part through the activation of
      membrane-associated MMPs. Nicotine and P. gingivalis had an additive effect on
      human gingival fibroblast-mediated collagen degradation.

PMID- 17451543
TI  - Identification of intracellular oral species within human crevicular epithelial
      cells from subjects with chronic periodontitis by fluorescence in situ
      hybridization.
AB  - BACKGROUND AND OBJECTIVE: Interactions between oral bacteria and gingival
      epithelial cells play an important role in the pathogenesis of periodontal
      diseases. This study used in situ hybridization with 16 rRNA probes and confocal
      microscopy to detect the periodontal pathogens Porphyromonas gingivalis,
      Actinobacillus actinomycetemcomitans, Tannerella forsythia, and Treponema
      denticola within epithelial cells from periodontal pockets, gingival crevice, and
      buccal mucosa collected from subjects with chronic periodontitis (n = 14) and
      good periodontal health (n = 8). MATERIAL AND METHODS: Each green fluorescent
      species-specific and universal probe was hybridized with all 58 epithelial
      samples from the 22 patients. The samples were observed by confocal microscopy to
      confirm the intracellular localization of oral species of bacteria. The mean
      frequency of detection and number of intracellular bacteria per epithelial cell
      were computed for each sample. RESULTS: The frequency of cells with internalized
      bacteria was higher in samples from the gingival crevice than in samples from the
      oral mucosa. Epithelial cells from all subjects harbored intracellular bacteria;
      however, patients with periodontitis presented significantly higher counts of
      bacteria per cell than periodontally healthy individuals (p < 0.05). Periodontal
      pathogens showed a trend to be detected in higher numbers in epithelial cells
      from periodontitis patients. In particular, T. forsythia and T. denticola were
      significantly more prevalent in periodontal pocket cells than healthy sulci and
      buccal cell samples in the periodontitis group (p < 0.05). CONCLUSION: Those
      findings indicate that crevicular and buccal cells present internalized bacteria,
      regardless of periodontal status. However, higher bacterial loads are detected in
      cells from subjects with periodontitis.

PMID- 17451544
TI  - Modulation of osteogenic potential by recombinant human bone morphogenic protein
      2 in human periodontal ligament cells: effect of serum, culture medium, and
      osteoinductive medium.
AB  - BACKGROUND AND OBJECTIVE: Bone morphogenic proteins are known, in animal models,
      to promote many developmental processes, including osteogenesis. Clinical trials
      are currently underway to evaluate the potential of bone morphogenic proteins to
      promote bone and periodontal regeneration in humans. The aim of this study was to
      establish an optimal cell culture condition for using to study the biological
      effects of recombinant human bone morphogenic protein-2 on periodontal ligament
      cells. MATERIAL AND METHODS: The roles of serum concentration, types of culture
      medium (alpha-modified essential medium or Dulbecco's modified Eagle's medium),
      the presence of osteoinductive medium (including dexamethasone, ascorbic acid and
      beta-glycerophosphate), and timing of addition of the osteoinductive medium and
      recombinant human bone morphogenic protein-2, on the expression of alkaline
      phosphatase were investigated in cultured periodontal ligament cells.
      Cytochemical stainings and biological assay of alkaline phosphatase were also
      demonstrated. RESULTS: Our results suggested that an increased concentration of
      serum might mask the effect of recombinant human bone morphogenic protein-2 on
      the expression of alkaline phosphatase in periodontal ligament cells. alpha
      Modified essential medium was found to induce a stronger cytochemical staining of
      the alkaline phosphatase than Dulbecco's modified Eagle's medium under similar
      culture conditions. Pre-incubation of cells with osteoinductive medium before the
      addition of various concentrations of recombinant human bone morphogenic protein
      2 enhanced greater alkaline phosphatase expression than the simultaneous presence
      of both osteoinductive medium and recombinant human bone morphogenic protein-2.
      CONCLUSION: The findings of this study suggest that the effect of recombinant
      human bone morphogenic protein-2 on periodontal ligament cells could be
      efficiently investigated after the proper selection of culture variables and
      temporal sequence of adding bioactive factors. The optimal culture condition
      identified in this study might be useful in further studies to elucidate the
      regulatory mechanism of periodontal ligament cells in periodontal regeneration
      after stimulation with recombinant human bone morphogenic protein-2.

PMID- 17451545
TI  - Susceptibility of type 2 diabetic mice to low-virulence bacterial infection:
      induction of abscess formation by gingipain-deficient Porphyromonas gingivalis.
AB  - BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus is considered an important
      risk factor of adult periodontitis. However, recent studies have revealed that
      the subgingival microbial flora of diabetes mellitus patients does not differ
      from that of healthy individuals. In this study, we examined the response of type
      2 diabetes mellitus hosts to low-virulence bacteria in a murine abscess model.
      MATERIAL AND METHODS: Porphyromonas gingivalis ATCC 33277 or KDP128 (rgpA rgpB
      kgp) were injected into two mouse strains - C57BL/6J and its derivative, KK/A(Y),
      which becomes diabetic spontaneously. RESULTS: Lesions of KK/A(Y) mice injected
      with either low-virulence P. gingivalis KDP128 or wild-type 33277 were
      significantly larger than those of C57BL/6J mice injected with the same strains.
      Histologically, more neutrophils and macrophages migrated to the lesions in the
      KK/A(Y) mice injected with P. gingivalis 33277 and KDP128 compared with those of
      C57BL/6J mice injected with the same respective strains. CONCLUSION: These
      results suggest that severe inflammation is observed in response to low-virulence
      bacteria in addition to the highly virulent bacteria in type 2 diabetes mellitus
      hosts.

PMID- 17451546
TI  - The effect of age on prostaglandin-synthesizing enzymes in the development of
      gingivitis.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to identify the expression of
      cyclooxygenase-1, cyclooxygenase-2, cyclooxygenase-3, and microsomal
      prostaglandin E synthase-1 in young and elderly subjects. MATERIAL AND METHODS:
      Periodontally healthy subjects were divided into young (18-30 years, n = 7) and
      elderly (46-77 years, n = 7). A gingival biopsy was taken at baseline. After
      experimental gingivitis, clinical examination was repeated and a second biopsy
      was taken. The expression of cyclooxygenase-1, cyclooxygenase-2, cyclooxygenase
      3, and microsomal prostaglandin E synthase-1 was analyzed by means of
      immunohistochemistry. RESULTS: In both healthy age groups, cyclooxygenase-1 and
      microsomal prostaglandin E synthase-1 were expressed in epithelial cells,
      endothelial cells and fibroblast-like connective tissue cells. Cyclooxygenase-1
      was found in Langerhans' cells of the epithelium. Cyclooxygenase-2 expression was
      observed in cells exhibiting the morphology of epithelial mitosis cells, and the
      expression of cyclooxygenase-2 in periodontally healthy elderly subjects was
      significantly lower (p < or = 0.05). Following experimental gingivitis,
      cyclooxygenase-1 and microsomal prostaglandin E synthase-1 expression did not
      change. However, the expression of cyclooxygenase-2 was significantly increased
      in both age groups (p < or = 0.05). Cyclooxygenase-3 was not detected in any
      group investigated. CONCLUSION: Cyclooxygenase-1 and microsomal prostaglandin E
      synthase-1 were expressed constitutively in gingival tissue, and expression was
      unaffected by age or inflammation states. In contrast, the expression of
      cyclooxygenase-2 was weaker in elderly subjects. In the course of experimental
      gingivitis, cyclooxygenase-2 was induced in both age groups.

PMID- 17451547
TI  - Cyclooxygenase-2 inhibitor reduces simvastatin-induced bone morphogenetic protein
      2 and bone formation in vivo.
AB  - BACKGROUND AND OBJECTIVE: Simvastatin, a cholesterol-lowering drug, also
      stimulates oral bone growth when applied topically, without systemic side
      effects. However, the mechanisms involved in vivo are not known. We hypothesized
      that bone morphogenetic protein-2, nitric oxide synthase, and cyclooxygenase-2
      are involved, based on prior in vitro evidence. MATERIAL AND METHODS: A rat
      bilateral mandible model, where 0.5 mg of simvastatin in methylcellulose gel was
      placed on one side and gel alone on the other, was used to quantify nitric oxide,
      cyclooxygenase-2 and bone morphogenetic protein-2 (via tissue extraction, enzyme
      activity or immunoassay), and to analyze the bone formation rate (via
      undecalcified histomorphometry). Cyclooxygenase-2 and nitric oxide synthase
      inhibitors (NS-398 and L-NAME, respectively) were administered intraperitoneally.
      RESULTS: Simvastatin was found to stimulate local bone morphogenetic protein-2,
      nitric oxide and the regional bone formation rate (p < 0.05), whereas NS-398
      inhibited bone morphogenetic protein-2 and reduced the bone formation rate (p <
      0.05). CONCLUSION: These data suggest an association between simvastatin-induced
      bone morphogenetic protein-2 and bone formation in the mandibular
      microenvironment, and the negative effect of cyclooxygenase-2 inhibitors on bone
      growth.

PMID- 17451548
TI  - Effects of periodontal therapy on serum C-reactive protein, sE-selectin, and
      tumor necrosis factor-alpha secretion by peripheral blood-derived macrophages in
      diabetes. A pilot study.
AB  - BACKGROUND AND OBJECTIVE: Diabetes is associated with an increased risk for
      vascular disease and periodontitis. The aim of this study was to assess the
      effects of periodontal treatment in diabetes with respect to alterations in the
      pro-inflammatory potential of peripheral blood mononuclear cells. MATERIAL AND
      METHODS: Ten patients with diabetes and moderate to severe periodontitis received
      full-mouth subgingival debridement. Blood samples for serum/plasma and
      mononuclear cell isolation were collected prior to and 4 wk after therapy.
      Mononuclear cells were analyzed by flow cytometry and stimulated with
      lipopolysaccharide or ionomycin/phorbol ester to determine the pro-inflammatory
      capacity of macrophages and lymphocytes, respectively. RESULTS: Following
      periodontal treatment, all patients demonstrated a significant improvement in
      clinical periodontal status (p < 0.05), despite only modest reduction in
      subgingival bacterial load or homologous serum immunoglobulin G titers. CD14(+)
      blood monocytes decreased by 47% (p < 0.05), and the percentage of macrophages
      spontaneously releasing tumor necrosis factor-alpha decreased by 78% (p < 0.05).
      There were no significant changes in the capacity of lymphocytes to secrete
      interferon-gamma. Among a number of serum inflammatory markers tested, high
      sensitivity-C-reactive protein significantly decreased by 37% (p < 0.01) and
      soluble E-selectin decreased by 16.6% (p < 0.05). CONCLUSION: These data suggest
      a reduced tendency for monocyte/macrophage-driven inflammation with periodontal
      therapy and a potential impact on atherosclerosis-related complications in
      diabetic individuals.

PMID- 17451549
TI  - Identification of marker genes distinguishing human periodontal ligament cells
      from human mesenchymal stem cells and human gingival fibroblasts.
AB  - BACKGROUND AND OBJECTIVE: Molecular gene markers, which can distinguish human
      bone marrow mesenchymal stem cells from human fibroblasts, have recently been
      reported. Messenger RNA levels of tissue factor pathway inhibitor-2, major
      histocompatibility complex-DR-alpha, major histocompatibility complex-DR-beta,
      and neuroserpin are higher in human bone marrow mesenchymal stem cells than in
      human fibroblasts. However, human bone marrow mesenchymal stem cells express less
      apolipoprotein D mRNA than human fibroblasts. Periodontal ligament cells are a
      heterogeneous cell population including fibroblasts, mesenchymal stem cells, and
      progenitor cells of osteoblasts or cementoblasts. The use of molecular markers
      that distinguish human bone marrow mesenchymal stem cells from human fibroblasts
      may provide insight into the characteristics of human periodontal ligament cells.
      In this study, we compared the molecular markers of human periodontal ligament
      cells with those of human bone marrow mesenchymal stem cells and human gingival
      fibroblasts. MATERIAL AND METHODS: The mRNA expression of the molecular gene
      markers was analyzed using real-time polymerase chain reaction. Statistical
      differences were determined with the two-sided Mann-Whitney U-test. RESULTS:
      Messenger RNA levels of major histocompatibility complex-DR-alpha and major
      histocompatibility complex-DR-beta were lower and higher, respectively, in human
      periodontal ligament cells than in human bone marrow mesenchymal stem cells or
      human gingival fibroblasts. Human periodontal ligament cells showed the lowest
      apolipoprotein D mRNA levels among the three types of cells. CONCLUSION: Human
      periodontal ligament cells may be distinguished from human bone marrow
      mesenchymal stem cells and human gingival fibroblasts by the genes for
      apolipoprotein D, major histocompatibility complex-DR-alpha, and major
      histocompatibility complex-DR-beta.

PMID- 17451550
TI  - Chloroplast division.
AB  - Chloroplasts are descendants of cyanobacteria and divide by binary fission.
      Several components of the division apparatus have been identified in the past
      several years and we are beginning to appreciate the plastid division process at
      a mechanistic level. In this review, we attempt to summarize the most recent
      developments in the field and assemble these observations into a working model of
      plastid division in plants.

PMID- 17451551
TI  - Immunogold labeling of cryosections from high-pressure frozen cells.
AB  - Immunogold labeling of cryosections according to Tokuyasu (Tokuyasu KT. A
      technique for ultracyotomy of cell suspensions and tissues. J Cell Biol
      1973;57:551-565), is an important and widely used method for immunoelectron
      microscopy. These sections are cut from material that is chemically fixed at room
      temperature (room temperature fixation, RTF). Lately in many morphological
      studies fast freezing followed by cryosubstitution fixation (CSF) is used instead
      of RTF. We have explored some new methods for applying immunogold labeling on
      cryosections from high-pressure frozen cells (HepG2 cells, primary chondrocytes)
      and tissues (cartilage and exocrine pancreas). As immunolabeling has to be
      carried out on thawed and stable sections, we explored two ways to achieve this:
      (1) The section fixation method, as briefly reported before (Liou W et al.
      Histochem Cell Biol 1996;106:41-58 and Mobius W et al. J Histochem Cytochem
      2002;50:43-55.) in which cryosections from freshly frozen cells were stabilized
      in mixtures of sucrose and methyl cellulose and varying concentrations of
      glutaraldehyde, formaldehyde and uranyl acetate (UA). Only occasionally does this
      method reveal section areas with excellent cell preservation and negatively
      stained membranes like Tokuyasu sections of RTF material. (Liou et al.) (2) The
      rehydration method, a novel approach, in which CSF with glutaraldehyde and/or
      osmium tetroxide (OsO4) was followed by rehydration and cryosectioning as in the
      Tokuyasu method. Especially, the addition of UA and low concentrations of water
      to the CSF medium favored superb membrane contrast. Immunogold labeling was as
      efficient as with the Tokuyasu method.

PMID- 17451552
TI  - The ternary Rab27a-Myrip-Myosin VIIa complex regulates melanosome motility in the
      retinal pigment epithelium.
AB  - The retinal pigment epithelium (RPE) contains melanosomes similar to those found
      in the skin melanocytes, which undergo dramatic light-dependent movements in fish
      and amphibians. In mammals, those movements are more subtle and appear to be
      regulated by the Rab27a GTPase and the unconventional myosin, Myosin VIIa
      (MyoVIIa). Here we address the hypothesis that a recently identified Rab27a- and
      MyoVIIa-interacting protein, Myrip, promotes the formation of a functional
      tripartite complex. In heterologous cultured cells, all three proteins co
      immunoprecipitated following overexpression. Rab27a and Myrip localize to the
      peripheral membrane of RPE melanosomes as observed by immunofluorescence and
      immunoelectron microscopy. Melanosome dynamics were studied using live-cell
      imaging of mouse RPE primary cultures. Wild-type RPE melanosomes exhibited either
      stationary or slow movement interrupted by bursts of fast movement, with a
      peripheral directionality trend. Nocodazole treatment led to melanosome
      paralysis, suggesting that movement requires microtubule motors. Significant and
      similar alterations in melanosome dynamics were observed when any one of the
      three components of the complex was missing, as studied in ashen- (Rab27a
      defective) and shaker-1 (MyoVIIa mutant)-derived RPE cells, and in wild-type RPE
      cells transduced with adenovirus carrying specific sequences to knockdown Myrip
      expression. We observed a significant increase in the number of motile
      melanosomes, exhibiting more frequent and prolonged bursts of fast movement, and
      inversion of directionality. Similar alterations were observed upon cytochalasin
      D treatment, suggesting that the Rab27a-Myrip-MyoVIIa complex regulates tethering
      of melanosomes onto actin filaments, a process that ensures melanosome movement
      towards the cell periphery.

PMID- 17451553
TI  - Ugo1p is a multipass transmembrane protein with a single carrier domain required
      for mitochondrial fusion.
AB  - The outer mitochondrial membrane protein Ugo1 forms a complex with the Fzo1p and
      Mgm1p GTPases that regulates mitochondrial fusion in yeast. Ugo1p contains two
      putative carrier domains (PCDs) found in mitochondrial carrier proteins (MCPs).
      Mitochondrial carrier proteins are multipass transmembrane proteins that actively
      transport molecules across the inner mitochondrial membrane. Mitochondrial
      carrier protein transport requires functional carrier domains with the consensus
      sequence PX(D/E)XX(K/R). Mutation of charged residues in this consensus sequence
      disrupts transport function. In this study, we used targeted mutagenesis to show
      that charge reversal mutations in Ugo1p PCD2, but not PCD1, disrupt mitochondrial
      fusion. Ugo1p is reported to be a single-pass transmembrane protein despite the
      fact that it contains several additional predicted transmembrane segments. Using
      a combination of protein targeting and membrane extraction experiments, we
      provide evidence that Ugo1p contains additional transmembrane domains and is
      likely a multipass transmembrane protein. These studies identify PCD2 as a
      functional domain of Ugo1p and provide the first experimental evidence for a
      multipass topology of this essential fusion component.

PMID- 17451554
TI  - Dileucine motif is sufficient for internalization and synaptic vesicle targeting
      of vesicular acetylcholine transporter.
AB  - Efficient cholinergic transmission requires accurate targeting of vesicular
      acetylcholine transporter (VAChT) to synaptic vesicles (SVs). However, the
      signals that regulate this vesicular targeting are not well characterized.
      Although previous studies suggest that the C-terminus of the transporter is
      required for its SV targeting, it is not clear whether this region is sufficient
      for this process. Furthermore, a synaptic vesicle-targeting motif (SVTM) within
      this sequence remains to be identified. Here we use a chimeric protein, TacA,
      between an unrelated plasma membrane protein, Tac, and the C-terminus of VAChT to
      demonstrate the sufficiency of the C-terminus for targeting to synaptic vesicle
      like vesicles (SVLVs) in PC12 cells. TacA shows colocalization and
      cosedimentation with the SV marker synaptophysin. Deletion mutation analysis of
      TacA demonstrates that a short, dileucine motif-containing sequence is required
      and sufficient to direct this targeting. Dialanine mutation analysis within this
      sequence suggests indistinguishable signals for both internalization and SV
      sorting. Using additional chimeras as controls, we confirm the specificity of
      this region for SVLVs targeting. Therefore, we suggest that the dileucine
      containing motif is sufficient as a dual signal for both internalization and SV
      targeting during VAChT trafficking.

PMID- 17451555
TI  - Molecular identification of 26 syntaxin genes and their assignment to the
      different trafficking pathways in Paramecium.
AB  - SNARE proteins have been classified as vesicular (v)- and target (t)-SNAREs and
      play a central role in the various membrane interactions in eukaryotic cells.
      Based on the Paramecium genome project, we have identified a multigene family of
      at least 26 members encoding the t-SNARE syntaxin (PtSyx) that can be grouped
      into 15 subfamilies. Paramecium syntaxins match the classical build-up of
      syntaxins, being 'tail-anchored' membrane proteins with an N-terminal cytoplasmic
      domain and a membrane-bound single C-terminal hydrophobic domain. The membrane
      anchor is preceded by a conserved SNARE domain of approximately 60 amino acids
      that is supposed to participate in SNARE complex assembly. In a phylogenetic
      analysis, most of the Paramecium syntaxin genes were found to cluster in groups
      together with those from other organisms in a pathway-specific manner, allowing
      an assignment to different compartments in a homology-dependent way. However,
      some of them seem to have no counterparts in metazoans. In another approach, we
      fused one representative member of each of the syntaxin isoforms to green
      fluorescent protein and assessed the in vivo localization, which was further
      supported by immunolocalization of some syntaxins. This allowed us to assign
      syntaxins to all important trafficking pathways in Paramecium.

PMID- 17451556
TI  - Stress-induced retrotranslocation of clusterin/ApoJ into the cytosol.
AB  - Clusterin is a usually secreted glycoprotein with chaperone properties. Recently,
      it has been suggested that clusterin isoforms reside in the nuclear and cytosolic
      compartments of human cell types, where they can influence various cellular
      programs including DNA repair, transcription and apoptosis. Several mechanisms
      have been proposed to explain this atypical location, including alternative
      transcription initiation and alternative splicing. However, none of these have
      been unequivocally established as occurring in live cells. Here we provide direct
      experimental evidence that in live intact cells, under certain stress conditions,
      clusterin can evade the secretion pathway and reach the cytosol. This was
      demonstrated using several complementary approaches. Flow cytometry and selective
      permeabilization of U251 cell membranes with digitonin allowed detection of
      cytosolic clusterin in stressed U251 cells. In addition, a stringent enzymatic
      assay reliant upon the exclusively cytosolic deubiquitinase enzymes confirmed
      that clusterin synthesized with its hydrophobic secretion signal sequence can
      reach the cytosol of U251 cells. The retrotranslocation of clusterin is likely to
      occur through a mechanism similar to the endoplasmic reticulum (ER)-associated
      protein degradation pathway and involves passage through the Golgi apparatus. We
      also report that the ER-associated ubiquitin ligase Hrd1/synoviolin can interact
      with, and ubiquitinate clusterin. The possible biological functions of these
      novel behaviours of clusterin are discussed.

PMID- 17451557
TI  - Multiple and stepwise interactions between coatomer and ADP-ribosylation factor-1
      (Arf1)-GTP.
AB  - The small GTPase ADP-ribosylation factor-1 (Arf1) plays a key role in the
      formation of coat protein I (COP I)-coated vesicles. Upon recruitment to the
      donor Golgi membrane by interaction with dimeric p24 proteins, Arf1's GDP is
      exchanged for GTP. Arf1-GTP then dissociates from p24, and together with other
      Golgi membrane proteins, it recruits coatomer, the heptameric coat protein
      complex of COP I vesicles, from the cytosol. In this process, Arf1 was shown to
      specifically interact with the coatomer beta and gamma-COP subunits through its
      switch I region, and with epsilon-COP. Here, we mapped the interaction of the
      Arf1-GTP switch I region to the trunk domains of beta and gamma-COP. Site
      directed photolabeling at position 167 in the C-terminal helix of Arf1 revealed a
      novel interaction with coatomer via a putative longin domain of delta-COP. Thus,
      coatomer is linked to the Golgi through multiple interfaces with membrane-bound
      Arf1-GTP. These interactions are located within the core, adaptor-like domain of
      coatomer, indicating an organizational similarity between the COP I coat and
      clathrin adaptor complexes.

PMID- 17451558
TI  - The role of cargo proteins in GGA recruitment.
AB  - Coat proteins are recruited onto membranes to form vesicles that transport cargo
      from one compartment to another, but the extent to which the cargo helps to
      recruit the coat proteins is still unclear. Here we have examined the role of
      cargo in the recruitment of Golgi-localized, gamma-ear-containing, ADP
      ribosylation factor (ARF)-binding proteins (GGAs) onto membranes in HeLa cells.
      Moderate overexpression of CD8 chimeras with cytoplasmic tails containing DXXLL
      sorting signals, which bind to GGAs, increased the localization of all three GGAs
      to perinuclear membranes, as observed by immunofluorescence. GGA2 was also
      expressed at approximately twofold higher levels in these cells because it was
      degraded more slowly. However, this difference only partially accounted for the
      increase in membrane localization because there was a approximately fivefold
      increase in GGA2 associated with crude membranes and a approximately 12-fold
      increase in GGA2 associated with clathrin-coated vesicles (CCVs) in cells
      expressing CD8-DXXLL chimeras. The effect of cargo proteins on GGA recruitment
      was reconstituted in vitro using permeabilized control and CD8-DXXLL-expressing
      cells incubated with cytosol containing recombinant GGA2 constructs. Together,
      these results demonstrate that cargo proteins contribute to the recruitment of
      GGAs onto membranes and to the formation of GGA-positive CCVs.

PMID- 17451559
TI  - Alcohol redirects CCK-mediated apical exocytosis to the acinar basolateral
      membrane in alcoholic pancreatitis.
AB  - The molecular mechanism of clinical alcohol-induced pancreatitis remains vague.
      We had reported that experimental high-dose cholecystokinin (CCK)-induced
      pancreatitis is in part because of excessive aberrant basolateral exocytosis.
      High-dose CCK caused Munc18c on basolateral plasma membrane (BPM) to dissociate
      from syntaxin (Syn)-4, activating Syn-4 to complex with plasma membrane (PM)-SNAP
      23 and granule-VAMP to mediate basolateral exocytosis. We now hypothesize that
      alcohol could render the acinar cell BPM conducive to exocytosis by a similar
      mechanism. Weakly stimulating postprandial doses of alcohol (20-50 mM) inhibited
      postprandial low-dose CCK-stimulated secretion by blocking physiologic apical
      exocytosis and redirecting exocytosis to less-efficient basal PM (visualized by
      FM1-43 fluorescence imaging) and lateral PM sites (electron microscopy). Alcohol
      or low-dose CCK had no effect on PM-Munc18c, but alcohol preincubation enabled
      low-dose CCK to displace Munc18c from BPM, leading to SNARE complex assembly in
      the BPM. Similarly, alcohol diet-fed rats did not exhibit morphologic defects in
      the pancreas nor affected PM-Munc18c behavior, but subsequent intraperitoneal
      injections of low-dose CCK analog cerulein caused Munc18c displacement from BPM
      and cytosolic degradation, which contributed to pancreatitis. We conclude that
      alcohol induces BPM-Munc18c to become receptive to postprandial CCK-induced
      displacement into the cytosol, a process which facilitates SNARE complex assembly
      that in turn activates restricted BPM sites to become available for aberrant
      exocytosis into the interstitial space, where zymogen activation would take place
      and cause pancreatitis.

PMID- 17451560
TI  - Review article: drug hepatotoxicity.
AB  - BACKGROUND: Drug toxicity is the leading cause of acute liver failure in the
      United States. Further understanding of hepatotoxicity is becoming increasingly
      important as more drugs come to market. AIMS: (i) To provide an update on recent
      advances in our understanding of hepatotoxicity of select commonly used drug
      classes. (ii) To assess the safety of these medications in patients with pre
      existing liver disease and in the post-liver transplant setting. (iii) To review
      relevant advances in toxicogenomics which contribute to the current understanding
      of hepatotoxic drugs. METHODS: A Medline search was performed to identify
      relevant literature using search terms including 'drug toxicity, hepatotoxicity,
      statins, thiazolidinediones, antibiotics, antiretroviral drugs and
      toxicogenomics'. RESULTS: Amoxicillin-clavulanic acid is one of the most
      frequently implicated causes of drug-induced liver injury worldwide. Statins
      rarely cause clinically significant liver injury, even in patients with
      underlying liver disease. Newer thiazolidinediones are not associated with the
      degree of liver toxicity observed with troglitazone. Careful monitoring for liver
      toxicity is warranted in patients who are taking antiretrovirals, especially
      patients who are co-infected with hepatitis B and C. Genetic polymorphisms among
      enzymes involved in drug metabolism and HLA types may account for some of the
      differences in individual susceptibility to drug hepatotoxicity. CONCLUSIONS:
      Drug-induced hepatotoxicity will remain a problem that carries both clinical and
      regulatory significance as long as new drugs continue to enter the market. Future
      results from ongoing multicentre collaborative efforts may help contribute to our
      current understanding of hepatotoxicity associated with drugs.

PMID- 17451561
TI  - Cochrane systematic review: pegylated interferon plus ribavirin vs. interferon
      plus ribavirin for chronic hepatitis C.
AB  - BACKGROUND: About 170 million patients worldwide have chronic hepatitis C.
      Pegylated interferon plus ribavirin is currently the recommended therapy. AIM: To
      evaluate the beneficial and harmful effects of pegylated interferon plus
      ribavirin vs. interferon plus ribavirin for chronic hepatitis C infection.
      METHODS: We searched The Cochrane Library, MEDLINE, EMBASE, LILACS, Science
      Citation Index Expanded and contacted pharmaceutical companies and authors of
      trials (to March 2005). RESULTS: We included 18 randomized clinical trials with
      4811 patients. Eleven trials (61%) had allocation bias risks and all had
      assessment bias risk because of lack of blinding. Compared with interferon plus
      ribavirin, pegylated interferon plus ribavirin had significant beneficial effects
      on sustained virological response [risk ratio (RR): 0.80; 95% CI: 0.74-0.88].
      Data were insufficient to determine impact on long-term outcomes. Pegylated
      interferon plus ribavirin significantly increased dose reductions (RR: 1.44; 95%
      CI: 1.14-1.82) and adverse events including neutropenia (RR: 2.25; 95% CI: 1.58
      3.21), thrombocytopenia (RR: 2.28; 95% CI: 1.14-4.54), arthralgia (RR: 1.19; 95%
      CI: 1.05-1.35), and injection-site reaction (RR: 2.56; 95% CI: 1.06-6.22).
      CONCLUSIONS: Pegylated interferon plus ribavirin compared with interferon plus
      ribavirin increased the proportion of patients with sustained virological
      response, but at the cost of more adverse events.

PMID- 17451562
TI  - Paroxetine for prevention of depressive symptoms induced by interferon-alpha and
      ribavirin for hepatitis C.
AB  - BACKGROUND: Whether antidepressants prevent depression during interferon
      alpha/ribavirin treatment for hepatitis C virus infection has yet to be
      established. AIM: To investigate the use of paroxetine in a prospective, double
      blind, placebo-controlled study for this indication. METHODS: Sixty-one hepatitis
      C virus-infected patients were randomly assigned to the antidepressant,
      paroxetine (n = 28), or placebo (n = 33), begun 2 weeks before and continued for
      24 weeks during interferon-alpha/ribavirin treatment. Primary endpoints included
      development of major depression and severity of depressive symptoms measured by
      the Montgomery Asberg Depression Rating Scale (MADRS). RESULTS: Rates of major
      depression during the study were low (17%) and did not differ between groups.
      Nevertheless, using published MADRS cut-off scores, the percent of subjects who
      met criteria for mild, moderate or severe depression during interferon
      alpha/ribavirin therapy was significantly lower in paroxetine- vs. placebo
      treated subjects (P = 0.02, Fisher's exact test). Assignment to paroxetine was
      also associated with significantly reduced depressive symptom severity. This
      effect was largely accounted for by participants with depression scores above the
      median (MADRS > 3) at baseline in whom paroxetine was associated with a maximal
      reduction in MADRS scores of 10.3 (95% CI: 2.1-18.5) compared with placebo at 20
      weeks (P < 0.01). Study limitations included a small sample size and high drop
      out rate. CONCLUSION: This double-blind, placebo-controlled trial provides
      preliminary data in support of antidepressant pre-treatment in hepatitis C virus
      patients with elevated depressive symptoms at baseline.

PMID- 17451563
TI  - The microbiological impact of pre-operative biliary drainage on patients
      undergoing hepato-biliary-pancreatic (HPB) surgery.
AB  - BACKGROUND: The merit of pre-operative biliary drainage in managing hepatic,
      biliary or pancreatic patients remains unclear with previous studies
      demonstrating significant increases in bacterobilia. AIMS: To establish if pre
      operative biliary drainage was associated with (i) a change in bacterial flora,
      (ii) post-operative sepsis and (iii) to ascertain if a modification of antibiotic
      prophylaxis was warranted. METHODS: Data were collected on 331 patients
      undergoing hepatic, biliary or pancreatic surgery for malignant obstruction
      between August 2000 and June 2005. Microbiological data from intra-operative
      bile, post-operative wounds, blood cultures, urine and sputum were analysed. All
      episodes of pre-operative endoscopic retrograde cholangiopancreatography (ERCP),
      stenting and percutaneous drainage were documented. RESULTS: One hundred and
      sixty two patients had ERCP prior to surgery and 154 had surgery only. In
      comparison to patients who had surgery alone stented patients had significantly
      increased rates of bacterobilia (40 vs. 85%) and fungobilia (8 vs. 34%, both P <
      0.001). Pre-operative biliary drainage significantly increased post-operative
      sepsis, wound infections and prolonged in-patient stay (P < 0.05). The most
      common organisms cultured were coliforms and enterococcus with percutaneous
      transhepatic cholangiography (PTC) highly significant for the development of MRSA
      sepsis. CONCLUSIONS: Pre-operative biliary drainage is associated with a high
      incidence of bacterobilia and fungal colonization. Pre-operative biliary drainage
      should be utilized selectively, with modification of antibiotic prophylaxis
      according to patient characteristics.

PMID- 17451564
TI  - The impact of insulin resistance, serum adipocytokines and visceral obesity on
      steatosis and fibrosis in patients with chronic hepatitis C.
AB  - AIMS: To assess whether host metabolic factors influence the degree of hepatic
      steatosis and fibrosis in patients infected with hepatitis C virus, and to
      evaluate the impact of anti-viral therapy on insulin resistance and serum levels
      of adipocytokines. METHODS: Clinical and biochemical features, anthropometrical
      characteristics, and levels of fasting insulin, leptin, adiponectin and resistin
      were measured in 'naive' patients with chronic hepatitis C, before, during and
      after therapy with Peg-Interferon-alpha 2a plus Ribavirin. RESULTS: Forty-eight
      patients were included (M/F 28/20; mean age 50.0 +/- 12.6 years; 62.5% genotype
      1). Body mass index was 26.4 +/- 4.0 kg/m(2), and visceral obesity was present in
      24 patients. At multivariate analysis (RR; 95% CI), steatosis was associated to
      older age (1.08; 1-1.18), necroinflammatory activity (17.67; 1.6-194.46), and
      raised insulin levels (1.39; 1.1-1.77). Fibrosis was related to necroinflammatory
      activity (25.73; 2.54-261.11), and steatosis (6.47; 1.09-38.29). Sustained viral
      response was achieved by 62.5% of patients and was associated with younger age
      (0.92; 0.85-0.99), genotype non-1 (10.61; 1.52-73.76) and absence of visceral
      obesity (13.78; 2.36-80.29). At the end of follow-up, insulin and the homeostasis
      model assessment for insulin resistance were reduced and adiponectin increased
      when compared with baseline, all unrelated to the outcome of treatment.
      CONCLUSIONS: Visceral obesity correlates with the degree of steatosis and
      fibrosis, and it negatively affects treatment response. Significant changes of
      insulin resistance and adipocytokines occur under treatment, irrespective of
      virological outcome.

PMID- 17451565
TI  - The role of genomic and antigenomic HCV-RNA strands as predictive factors of
      response to pegylated interferon plus ribavirin therapy.
AB  - BACKGROUND: Hepatitis C virus replicates by the synthesis of an antigenomic HCV
      RNA. As the end point of anti-viral therapy is to decrease viral replication, the
      amount of antigenomic HCV-RNA could influence the response. AIM: To study if
      amounts of genomic and antigenomic HCV-RNA in the baseline liver biopsy are
      predictive factors of response to anti-viral therapy. METHODS: Eighty-eight
      patients with chronic HCV infection (anti-HIV-negative) treated with pegyltaed
      interferon-alpha2b plus ribavirin for 12 months were included. Intrahepatic
      genomic and antigenomic HCV-RNA concentrations were determined by real-time
      polymerase chain reaction and percentage of infected hepatocytes by in situ
      hybridization. RESULTS: Of the 88 patients, 31% were responders while 69% were
      not. Median of antigenomic HCV-RNA in liver of responders and non-responders was
      120 000 copies/microg RNA (range: 10,000-775,000) vs. 150,000 copies/microg RNA
      (range: 100-3,200,000; P = 0.38). Median of genomic HCV-RNA in liver of
      responders was 1,250,000 copies/microg RNA (range: 5000-9,000,000) and in non
      responders 3,180,000 copies/microg RNA (range: 4600-18,000,000; P = 0.0191).
      Predictive factors of response in the logistic regression were: intrahepatic
      amount of genomic HCV-RNA, percentage of infected hepatocytes and previous
      therapy. CONCLUSION: Response to 12 months of therapy with pegylated interferon
      alpha2b plus ribavirin depends on the amount of genomic HCV-RNA in the pre
      treatment liver biopsy.

PMID- 17451566
TI  - Risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in patients with
      unexplained chest/epigastric pain and normal upper endoscopy: a 10-year Danish
      cohort study.
AB  - BACKGROUND: No studies have examined the risk of upper gastrointestinal diseases
      among patients with unexplained chest/epigastric pain (UCEP) and a normal upper
      endoscopy. AIM: To examine the relative risk of peptic ulcer, oesophagitis,
      pancreatitis or gallstone in UCEP patients. METHODS: This Danish 10-year cohort
      study focused on UCEP patients (n = 386), diagnosed in 1992-93. Ten age- and
      gender-matched controls were selected per patient from Denmark's Civil
      Registration System (n = 3860). Kaplan-Meier analysis and Cox's regression
      analysis was used to calculate the risk of hospitalization for peptic ulcer,
      oesophagitis, pancreatitis or gallstone. RESULTS: Compared with controls, the
      adjusted relative risks among UCEP patients <1 and > or = 1 year after upper
      endoscopy were for peptic ulcer 2.0 [95% confidence interval (CI) 0.2-18.4] and
      1.7 (95% CI 0.9-3.4), for oesophagitis 8.2 (95% CI 1.2-59.2) and 1.9 (95% CI 0.7
      5.0), for pancreatitis 9.2 (95% CI 2.0-41.8) and 3.9 (95% CI 1.4-10.5), and for
      gallstone 14.1 (95% CI 5.4-37.2) and 3.3 (95% CI 1.9-5.8). CONCLUSIONS: UCEP is
      positively associated with all study outcomes especially in the first year after
      upper endoscopy, indicating that peptic ulcer, oesophagitis, pancreatitis or
      gallstone could be underlying early UCEP symptoms. However, the long-term
      association remained strong for pancreatitis and gallstone, suggesting a genuine
      excess risk.

PMID- 17451567
TI  - Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib
      compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy.
AB  - BACKGROUND: Small bowel mucosal injury associated with non-selective non
      steroidal anti-inflammatory drugs is being increasingly recognized. AIM: To
      evaluate the incidence of small bowel injury in healthy subjects receiving
      celecoxib or ibuprofen plus omeprazole using video capsule endoscopy (VCE).
      METHODS: Subjects with normal baseline VCE were randomly assigned to receive
      celecoxib 200 mg b.d., ibuprofen 800 mg t.d.s. plus omeprazole 20 mg o.d. or
      placebo for 2 weeks. The primary end point was mean number of small bowel mucosal
      breaks per subject. Secondary end points included correlation of faecal
      calprotectin levels with the primary outcome. RESULTS: After treatment, the mean
      number of small bowel mucosal breaks per subject and the percentage of subjects
      with mucosal breaks were 0.7/25.9% for ibuprofen/omeprazole compared with
      0.2/6.4% for celecoxib and 0.1/7.1% placebo (both comparisons P < 0.001). There
      were no significant differences between celecoxib and placebo in any measure.
      Mean increases in faecal calprotectin levels were higher in subjects receiving
      ibuprofen/omeprazole compared with celecoxib (P < 0.001), but no correlation was
      determined between these levels and small bowel mucosal breaks. CONCLUSIONS:
      Among healthy subjects with no baseline endoscopic lesions, celecoxib was
      associated with significantly fewer small bowel mucosal breaks than
      ibuprofen/omeprazole as assessed by VCE.

PMID- 17451568
TI  - Temporal trends in new and recurrent oesophageal strictures in a Medicare
      population.
AB  - BACKGROUND: The widespread use of proton pump inhibitors for gastro-oesophageal
      reflux disease could result in a decline in new as well as recurrent gastro
      oesophageal reflux disease-related oesophageal strictures. The temporal trends of
      strictures have not been examined in population-based studies. METHODS: To
      examine the temporal trends in strictures, we calculated the age-adjusted
      incidence rates of new oesophageal strictures with or without oesophageal
      dilation in a sample of Medicare beneficiaries between 1992 and 2000. We also
      examined recurrent dilations recorded at least 3 months after a new stricture or
      the preceding recurrent stricture. RESULTS: The age-adjusted rates for strictures
      accompanied with dilation declined by approximately 11% from 215 per million to
      192 per million. New oesophageal strictures with dilation declined as a
      proportion of all upper endoscopies procedures (from 2.6% to 1.9%). Recurrent
      dilation within 1 year declined dramatically from 16% (9.5% CI: 12.5-20.3) in
      1992 to 8% (95% CI: 4.43-10.62) in 2000. In multivariable proportional hazards
      model, there was a 30% risk reduction of recurrent oesophageal strictures.
      CONCLUSIONS: This population-based study indicates that the incidence of new as
      well as recurrent oesophageal strictures has been declining. In the face of
      rising incidence of other gastro-oesophageal reflux disease-related
      complications, it is important to understand the explanation of the present
      observations.

PMID- 17451569
TI  - Oral budesonide in the treatment of chronic refractory pouchitis.
AB  - BACKGROUND: Pouchitis is the major long-term complication after ileal-pouch nal
      anastomosis for ulcerative colitis. Ten to 15% of patients develop a chronic
      pouchitis, either treatment responsive or treatment refractory. AIM: To evaluate
      the efficacy of oral budesonide in inducing remission and improving quality of
      life in patients with chronic refractory pouchitis. METHODS: Twenty consecutive
      patients with active pouchitis, not responding after 1 month of antibiotic
      treatment were treated with budesonide controlled ileal release 9 mg/day for 8
      weeks. Symptomatic, endoscopic and histological evaluations were undertaken
      before and after treatment according to Pouchitis Disease Activity Index.
      Remission was defined as a combination of Pouchitis Disease Activity Index
      clinical score of < or = 2, endoscopic score of < or = 1 and total Pouchitis
      Disease Activity Index score of < or = 4. The quality of life was assessed with
      the Inflammatory Bowel Disease Questionnaire. RESULTS: Fifteen of 20 patients
      (75%) achieved remission. The median total Pouchitis Disease Activity Index
      scores before and after therapy were, respectively, 14 (range 9-16) and 3 (range
      2-10) (P < 0.001). The median Inflammatory Bowel Disease Questionnaire score also
      significantly improved from 105 (range 77-175) to 180 (range 85-220) (P < 0.001).
      CONCLUSION: Eight-week treatment with oral budesonide appears effective in
      inducing remission in patients with active pouchitis refractory to antibiotic
      treatment in this open-label study.

PMID- 17451570
TI  - Persistent small bowel mucosal villous atrophy without symptoms in coeliac
      disease.
AB  - BACKGROUND: Refractory sprue with malabsorption carries a risk of lymphoma. AIM:
      To examine whether a good clinical but poor histological response during a strict
      gluten-free diet predicts a poor outcome. METHODS: The study involved all coeliac
      patients who showed no histological recovery within 2 years on a strict gluten
      free diet. Small intestinal biopsy and bone mineral density were investigated in
      2001 and clinical features were followed up until 2005. The results were compared
      to those in 18 coeliac patients with a good histological recovery. RESULTS:
      Thirteen coeliac patients had persistent small intestinal villous atrophy despite
      maintaining gluten-free diet. All had demonstrated a good clinical response.
      Osteoporosis was found in 58% and 22% of the non-responders and responders,
      respectively (P = 0.04). In 2005, two of the non-responders had developed
      symptomatic refractory sprue, one died of lymphoma and one of carcinoid tumour,
      and one gastric adenocarcinoma was operated. None of the 18 controls had
      developed refractory sprue or malignancy. The frequency of histological non
      responsive disease was 1.9%. CONCLUSIONS: Persistent villous atrophy in adult
      coeliac disease, even in the absence of symptoms, carries a risk of subsequent
      severe complications. The follow-up biopsy is important in detecting these
      individuals.

PMID- 17451571
TI  - Publication of a negative trial without disclosing the drug.

PMID- 17451574
TI  - Fractional photothermolysis: a novel aesthetic laser surgery modality.
AB  - The ubiquity of increased sun exposure, oral contraceptives, and phototoxic drugs
      has led to an increased prevalence of conditions such as dyschromia, melasma,
      rhytides, and other signs of photoaging over the past few decades. Through the
      application of selective photothermolysis, laser surgery has attempted to create
      therapeutic options for these medically recalcitrant conditions. To date,
      however, this technology has been met with limited success, due to a high
      incidence of posttreatment side effects, inability to treat off the face, and a
      safety profile tailored to Fitzpatrick skin types I to III. More recently, a
      novel approach coined "fractional photothermolysis" was developed in an attempt
      to overcome these limitations. This new laser treatment modality has allowed for
      effective treatment of a diverse array of dermatologic conditions on and off the
      face with a wider therapeutic index and improved safety profile independent of
      Fitzpatrick skin type. This review sheds light on the technical aspects, biologic
      mechanisms, and clinical effects of fractional photothermolysis that help set it
      apart from previous modes of laser surgery.

PMID- 17451575
TI  - A randomized trial to determine the influence of laser therapy, monopolar
      radiofrequency treatment, and intense pulsed light therapy administered
      immediately after hyaluronic acid gel implantation.
AB  - BACKGROUND: Hyaluronic acid-based dermal fillers, such as hyaluronic acid gel
      (Restylane, Q-Medical AB, Uppsala, Sweden), are widely used for tissue
      augmentation of the nasolabial folds. Additional dermatologic treatments using
      infrared light, radiofrequency (RF), and intense pulsed light (IPL) are also
      important tools for facial rejuvenation. This study was designed to evaluate
      whether these therapies could be safely administered immediately after hyaluronic
      acid gel treatment without compromising the effect of the dermal filler.
      OBJECTIVE: The objective of this study was to confirm or refute any possible
      subtractive effects of augmentation of the nasolabial folds when followed by
      1,320-nm Nd:YAG laser, 1,450-nm diode laser, monopolar RF, and/or IPL treatments.
      METHODS: Thirty-six patients with prominent nasolabial folds were treated with
      hyaluronic acid gel implantation on one side of the face and hyaluronic acid gel
      followed by one of the nonablative laser/RF/IPL therapies on the contralateral
      side of the face. RESULTS: There were no statistically significant differences
      between wrinkle severity or global aesthetic scores for hyaluronic acid gel
      implantation alone and hyaluronic acid gel with laser/RF/IPL treatment at any
      time point. In a small sample, histologic changes were not apparent after
      laser/RF/IPL treatment. CONCLUSIONS: Based on this small pilot study, laser, RF,
      and IPL treatments can safely be administered immediately after hyaluronic acid
      gel implantation without reduction in overall clinical effect.

PMID- 17451576
TI  - The use of hybrid radiofrequency device for the treatment of rhytides and lax
      skin.
AB  - BACKGROUND: Recently, radiofrequency (RF) devices have been introduced and
      commercialized for nonablative procedures in dermatology and plastic surgery for
      the treatment of age-related rhytides and lax skin. OBJECTIVE: The objective was
      to assess the efficacy and safety of a novel RF device (Accent, Alma Lasers, Ltd,
      Caesarea, Israel) for the treatment of rhytides and lax skin. METHODS AND
      MATERIALS: Sixteen female patients (age range, 29-66 years; mean, 47+/-6 years;
      skin phototypes II to IV) were treated with Accent system. Patients were treated
      on the chin (n=5), forehead (n=8), cheeks (n=12), jowl lines (n=9), periorbital
      area (n=7), marionette line (n=3), and nasolabial folds (n=6) for wrinkles (n=27
      cases) and skin laxity (n=23 cases). Patients received two to six treatments
      (mean, 4.3+/-1.1), with the time interval of 2 to 3 weeks. Photographs were
      assessed 1 month after the last treatment. RESULTS For wrinkles and skin laxity,
      in 5 patients (42%), the cheeks (n=12) scored 51% to 75% (significant
      improvement), and 2 patients (17%), 76% to 100% (excellent improvement). For the
      jowl lines (n=9), 4 patients (44%) scored 51% to 75% (significant improvement),
      and 1 patient scored 76% to 100% (excellent improvement) for lax skin. For
      wrinkles on the periorbital (n=7) and forehead areas (n=8), three patients (37%)
      scored 51% to 75% (significant improvement). CONCLUSION: The Accent system is an
      effective and safe modality for the improvement of age-related rhytides and lax
      skin.

PMID- 17451577
TI  - Comparison of stacked pulses versus double-pass treatments of facial acne with a
      1,450-nm laser.
AB  - BACKGROUND: Although effective as a monotherapy for the treatment of inflammatory
      acne, the 1,450-nm diode laser is associated with considerable pain at higher
      fluences. MATERIALS AND METHODS: Eleven subjects were treated with a 1,450-nm
      diode laser in a split-face bilateral paired acne study. One-half of the face
      received a single-pass consisting of stacked double pulses. The other side
      received a double-pass treatment of single pulses. Settings were 11 J/cm(2) or
      lower as tolerated with appropriate dynamic cooling device (range 25-35).
      RESULTS: The mean pain rating was 5.33 on a 0 to 10 scale on the stacked-pulse
      treatment side and 5.12 on the double-pass side. Blinded reduction in mean acne
      lesion counts were 57.6% and 49.8% reduction, respectively. An overall acne scar
      improvement was seen in 83% of subjects with acne scarring. Transient
      hyperpigmentation occurred in two patients on the stacked pulse side and
      completely resolved without sequelae. CONCLUSIONS: The pulsed 1,450-nm diode
      laser can be used at lower fluences that elicit less discomfort yet effectively
      improve inflammatory acne. Stacking pulses appears to render a slightly higher
      efficacy than the multipass technique. Single-pulse, multiple-pass treatments may
      have a lower risk of cryogen-induced transient hyperpigmentation compared to
      standard high fluence techniques.

PMID- 17451578
TI  - Efficacy of pulsed dye laser in facial port-wine stains in Indian patients.
AB  - BACKGROUND: Facial port-wine stain (PWS) produces severe cosmetic disfigurement
      and pulsed dye laser (PDL) has revolutionized the treatment of PWS. OBJECTIVE: To
      assess the efficacy of PDL for facial PWS in Indian patients. MATERIALS AND
      METHODS: Twenty-seven patients of Fitzpatrick skin types IV and V in the age
      group of 8 to 34 years (mean 21.6 years), with lesional size 3 x 1.5 to 25 x 19
      cm and color from light pink to deep red and violaceous, were recruited. Laser
      parameters were spot size, 7 mm; fluence, 5 to 7.5 J/cm(2); wavelength, 585 nm,
      pulse duration, 0.45 ms; along with continuous air cooling. Response at every
      session was graded from 0 to 5+(0, no improvement; 1+, up to 25%; 2+, 26% to 50%;
      3+, 51% to 75%; 4 +, 76% to 99%; 5+, 100% lightening). RESULTS: In a total of 170
      sessions, maximum response of 1+ was observed in 6 patients after mean of 3.5
      sessions, 2+ in 8 patients after mean of 5.25 sessions, 3+ in 8 patients after
      mean of 7 sessions, and 4+ improvement in 5 patients after mean of 4.8 sessions.
      No patient showed complete clearance. Seven patients developed hyperpigmentation
      while 1 patient showed hypopigmentation, but none had textural change or
      scarring. CONCLUSION: PDL offers significant cosmetic improvement in facial PWS
      in Indian patients.

PMID- 17451579
TI  - A randomized, evaluator-blinded, two-center study of the safety and effect of
      volume on the diffusion and efficacy of botulinum toxin type A in the treatment
      of lateral orbital rhytides.
AB  - BACKGROUND: There has been considerable discussion about the effect of the degree
      of dilution of botulinum toxin (BTX) but very few scientific studies. OBJECTIVE:
      The objective was to observe as to whether a fivefold difference in concentration
      of BTX solution would produce a difference in clinical effect or duration of
      effect. METHODS AND MATERIALS: Twenty individuals were enrolled at two sites and
      a within-subject paired-comparison study was performed on the lateral orbital
      area with a single injection of 5 U of BTX (BOTOX Cosmetic, Allergan Inc.,
      Irvine, CA). The results were assessed both clinically and using a computer
      assisted estimation of the degree of wrinkling. RESULTS: No statistically
      significant differences were observed between the two sides. CONCLUSIONS: This is
      a small study and it may be that dilution does affect BTX result. We were,
      however, unable to detect any difference in this study, which suggests that the
      degree of dilution, at least within a fivefold margin, has only a small effect on
      the results of BTX injection in the lateral orbital area.

PMID- 17451580
TI  - Autologous fat transfer for periorbital rejuvenation: indications, technique, and
      complications.
AB  - BACKGROUND: The periorbital region is one of the first facial regions to show
      signs of aging. Traditional surgical approaches consisted of lifting and
      excisional procedures including brow lifts and blepharoplasties. Suboptimal
      results, however, have led surgeons to reassess their approach to the periorbita
      to address volume loss. OBJECTIVE: In this article, we review the shortcomings of
      brow lifting and blepharoplasty procedures and discuss the volume loss that
      occurs with aging. We present our approach of rejuvenating the periorbital region
      through volume restoration using autologous fat transplantation. MATERIALS AND
      METHODS: A review of fat transfer technique for the periorbital region is
      presented. RESULTS: Before and after photos are presented demonstrating
      periorbital rejuvenation. CONCLUSION: Surgeons performing cosmetic surgery should
      reconsider their approach to the periorbital region and enhance their results
      through autologous fat transplantation.

PMID- 17451581
TI  - Surgical excision versus curettage plus cryosurgery in the treatment of basal
      cell carcinoma.
AB  - BACKGROUND: Both cryosurgery, with and without prior curettage, and surgical
      excision (SE) are common therapeutic strategies for basal cell carcinoma (BCC).
      OBJECTIVE: The objective was to compare the efficacy between curettage plus
      cryosurgery (C&C) and SE in nonaggressive BCC of the head and neck. MATERIALS AND
      METHODS: A randomized controlled trial was carried out, in which tumors were
      assigned to either C&C (n=51) or SE (n=49). C&C was performed with a double
      freeze-thaw cycle after prior curettage of the tumor. SE was performed with a
      margin of 3 mm and with delayed histologic examination. RESULTS: Recurrences
      occurred 9 times after C&C (17.6%) and 4 times after SE (8.2%). The overall 5
      year recurrence probability was 19.6% for C&C and 8.4% for SE (p=.10). A hazard
      ratio of 2.57 (95% CI, 0.79-8.34) indicated a putative, but not statistically
      significant, advantage of SE. CONCLUSION: These data reflect the outcome of the
      first randomized controlled trial with long-term follow-up in the treatment of
      BCC, comparing C&C with SE. Although not statistically significantly different,
      the observed differences could still be of clinical relevance. Owing to the trend
      toward lower recurrence rates, better cosmetic results, and reduced wound healing
      time, we believe that SE should be preferred to C&C in the treatment of primary,
      nonaggressive BCC of the head and neck.

PMID- 17451582
TI  - Electronic templates versus dictation for the completion of Mohs micrographic
      surgery operative notes.
AB  - BACKGROUND: Operative notes can be generated electronically by manual input of
      the entire note, free-form oral dictation, or using either an electronic template
      or a template for dictation. There are few studies that have directly compared
      these modalities in terms of speed, accuracy, and completeness. OBJECTIVE: The
      objective was to determine whether electronic templates are more efficient and
      reduce errors compared to free-form oral dictation for the completion of Mohs
      micrographic surgery operative notes. METHODS: Operative notes for 110
      consecutive Mohs micrographic surgery cases were completed either by oral
      dictation or by electronic template. The time to dictate or complete the template
      was recorded for each note. Notes were subsequently edited, recording the number
      and type of errors as well as the time required to edit each note. RESULTS:
      Compared with dictation, operative notes completed with the electronic template
      had fewer errors (5.8% vs. 81%), took less time to complete (175.5 seconds vs.
      240.0 seconds), took less time to review and edit (41.6 seconds vs. 201.1
      seconds), and were completed and signed in a more timely fashion (0.115 days vs.
      20.7 days). CONCLUSION: Electronic templates are a more accurate and rapid method
      compared to free-form oral dictation for the completion of Mohs micrographic
      surgery operative notes and have the advantage of being immediately available to
      review and sign.

PMID- 17451583
TI  - A rare presentation of giant pilomatricoma located on the back.

PMID- 17451584
TI  - Novel technique to decrease cost of surgical light handle covers.

PMID- 17451585
TI  - Repair of two large adjacent cheek wounds.

PMID- 17451586
TI  - Clinical and dermoscopic characteristics of melanocytic nevi in Turkish children
      and their relationship with environmental and constitutional factors.
AB  - BACKGROUND/AIM: The number of melanocytic nevi strongly influences risk of
      melanoma. Researchers have therefore been prompted to study the epidemiology of
      nevi, particularly in children. Our aim was to determine the clinical and
      dermoscopic characteristics of melanocytic nevi in Turkish children and their
      relationship with environmental factors. METHODS: A total of 180 children were
      randomly included in the study. A survey was applied including age, sex, sunblock
      use, sunburn history, mother's dressing style, mother's education, and income.
      Dermoscopic patterns of nevi were noted. RESULTS: A total of 1,173 melanocytic
      nevi were examined. The mean number of nevi was 6.53+/-7.18. The number of
      melanocytic nevi significantly increased with age (Pearson r=0.616, p=.001). The
      most common localization was head and neck. A total of 81.1% of children had
      never used sunblock, and 57.2% of mothers dressed in the Islamic style. The mean
      number of melanocytic nevi in children whose mothers dressed in the Islamic style
      was lower than whose mothers dressed in non-Islamic style (p=.015). Sunblock use
      increased with mother's education (p=.001) and with income (p=.001). Children
      with more melanocytic nevi used more sunblock (p=.002), and sunblock use
      increased with age (p=.026). The most common dermoscopic feature was a globular
      pattern. CONCLUSION: This study lays the foundation for future studies showing
      the relationship between nevus phenotype, dermoscopic pattern, and social
      factors.

PMID- 17451587
TI  - The natural history of polymethylmethacrylate microspheres granulomas.

PMID- 17451588
TI  - Localized hypertrichosis after intense pulsed light treatment for tattoo removal.

PMID- 17451589
TI  - Recurrence of lentigo maligna after initial complete response to treatment with
      5% imiquimod cream.

PMID- 17451590
TI  - Cutaneous leiomyosarcoma: a tumor of the head and neck.

PMID- 17451591
TI  - Cutaneous metastasis of leiomyosarcoma.

PMID- 17451592
TI  - Surgical management of giant condyloma acuminatum (Buschke-Loewenstein tumor) of
      the perianal region.

PMID- 17451593
TI  - Nonhealing ulcer misinterpreted as a complication after varicose exeresis.

PMID- 17451594
TI  - A case of lymphangioma circumscriptum developed on the finger.

PMID- 17451595
TI  - Anthroposophic medical therapy in chronic disease: a four-year prospective cohort
      study.
AB  - BACKGROUND: The short consultation length in primary care is a source of concern,
      and the wish for more consultation time is a common reason for patients to seek
      complementary medicine. Physicians practicing anthroposophic medicine have
      prolonged consultations with their patients, taking an extended history,
      addressing constitutional, psychosocial, and biographic aspect of patients'
      illness, and selecting optimal therapy. In Germany, health benefit programs have
      included the reimbursement of this additional physician time. The purpose of this
      study was to describe clinical outcomes in patients with chronic diseases treated
      by anthroposophic physicians after an initial prolonged consultation. METHODS: In
      conjunction with a health benefit program in Germany, 233 outpatients aged 1-74
      years, treated by 72 anthroposophic physicians after a consultation of at least
      30 min participated in a prospective cohort study. Main outcomes were disease
      severity (Disease and Symptom Scores, physicians' and patients' assessment on
      numerical rating scales 0-10) and quality of life (adults: SF-36, children aged 8
      16: KINDL, children 1-7: KITA). Disease Score was documented after 0, 6 and 12
      months, other outcomes after 0, 3, 6, 12, 18, 24, and (Symptom Score and SF-36)
      48 months. RESULTS: Most common indications were mental disorders (17.6% of
      patients; primarily depression and fatigue), respiratory diseases (15.5%), and
      musculoskeletal diseases (11.6%). Median disease duration at baseline was 3.0
      years (interquartile range 0.5-9.8 years). The consultation leading to study
      enrolment lasted 30-60 min in 51.5% (120/233) of patients and > 60 min in 48.5%.
      During the following year, patients had a median of 3.0 (interquartile range 1.0
      7.0) prolonged consultations with their anthroposophic physicians, 86.1%
      (167/194) of patients used anthroposophic medication. All outcomes except KITA
      Daily Life subscale and KINDL showed significant improvement between baseline and
      all subsequent follow-ups. Improvements from baseline to 12 months were: Disease
      Score from mean (standard deviation) 5.95 (1.74) to 2.31 (2.29) (p < 0.001),
      Symptom Score from 5.74 (1.81) to 3.04 (2.16) (p < 0.001), SF-36 Physical
      Component Summary from 44.01 (10.92) to 47.99 (10.43) (p < 0.001), SF-36 Mental
      Component Summary from 42.34 (11.98) to 46.84 (10.47) (p < 0.001), and KITA
      Psychosoma subscale from 62.23 (19.76) to 76.44 (13.62) (p = 0.001). All these
      improvements were maintained until the last follow-up. Improvements were similar
      in patients not using diagnosis-related adjunctive therapies within the first six
      study months. CONCLUSION: Patients treated by anthroposophic physicians after an
      initial prolonged consultation had long-term reduction of chronic disease
      symptoms and improvement of quality of life. Although the pre-post design of the
      present study does not allow for conclusions about comparative effectiveness,
      study findings suggest that physician-provided anthroposophic therapy may play a
      beneficial role in the long-term care of patients with chronic diseases.

PMID- 17451596
TI  - Eurythmy therapy in chronic disease: a four-year prospective cohort study.
AB  - BACKGROUND: Many patients with chronic diseases use complementary therapies,
      often provided by their physicians. In Germany, several physician-provided
      complementary therapies have been reimbursed by health insurance companies as
      part of health benefit programs. In most of these therapies, the patient has a
      predominantly passive role. In eurythmy therapy, however, patients actively
      exercise specific movements with the hands, the feet or the whole body. The
      purpose of this study was to describe clinical outcomes in patients practising
      eurythmy therapy exercises for chronic diseases. METHODS: In conjunction with a
      health benefit program, 419 outpatients from 94 medical practices in Germany,
      referred to 118 eurythmy therapists, participated in a prospective cohort study.
      Main outcomes were disease severity (Disease and Symptom Scores, physicians' and
      patients' assessment on numerical rating scales 0-10) and quality of life
      (adults: SF-36, children aged 8-16: KINDL, children 1-7: KITA). Disease Score was
      documented after 0, 6 and 12 months, other outcomes after 0, 3, 6, 12, 18, 24,
      and (SF-36 and Symptom Score) 48 months. RESULTS: Most common indications were
      mental disorders (31.7% of patients; primarily depression, fatigue, and childhood
      emotional disorder) and musculoskeletal diseases (23.4%). Median disease duration
      at baseline was 3.0 years (interquartile range 1.0-8.5). Median number of
      eurythmy therapy sessions was 12 (interquartile range 10-19), median therapy
      duration was 119 days (84-188). All outcomes improved significantly between
      baseline and all subsequent follow-ups (exceptions: KITA Psychosoma in first
      three months and KINDL). Improvements from baseline to 12 months were: Disease
      Score from mean (standard deviation) 6.65 (1.81) to 3.19 (2.27) (p < 0.001),
      Symptom Score from 5.95 (1.75) to 3.49 (2.12) (p < 0.001), SF-36 Physical
      Component Summary from 43.13 (10.25) to 47.10 (9.78) (p < 0.001), SF-36 Mental
      Component Summary from 38.31 (11.67) to 45.01 (11.76) (p < 0.001), KITA
      Psychosoma from 69.53 (15.45) to 77.21 (13.60) (p = 0.001), and KITA Daily Life
      from 59.23 (21.78) to 68.14 (18.52) (p = 0.001). All these improvements were
      maintained until the last follow-up. Improvements were similar in patients not
      using diagnosis-related adjunctive therapies within the first six study months.
      Adverse reactions to eurythmy therapy occurred in 3.1% (13/419) of patients. No
      patient stopped eurythmy therapy due to adverse reactions. CONCLUSION: Patients
      practising eurythmy therapy exercises had long-term improvement of chronic
      disease symptoms and quality of life. Although the pre-post design of the present
      study does not allow for conclusions about comparative effectiveness, study
      findings suggest that eurythmy therapy can be useful for patients motivated for
      this therapy.

PMID- 17451597
TI  - Treatment of posttraumatic and focal osteoarthritic cartilage defects of the knee
      with autologous polymer-based three-dimensional chondrocyte grafts: 2-year
      clinical results.
AB  - Autologous chondrocyte implantation (ACI) is an effective clinical procedure for
      the regeneration of articular cartilage defects. BioSeed-C is a second-generation
      ACI tissue engineering cartilage graft that is based on autologous chondrocytes
      embedded in a three-dimensional bioresorbable two-component gel-polymer scaffold.
      In the present prospective study, we evaluated the short-term to mid-term
      efficacy of BioSeed-C for the arthrotomic and arthroscopic treatment of
      posttraumatic and degenerative cartilage defects in a group of patients suffering
      from chronic posttraumatic and/or degenerative cartilage lesions of the knee.
      Clinical outcome was assessed in 40 patients with a 2-year clinical follow-up
      before implantation and at 3, 6, 12, and 24 months after implantation by using
      the modified Cincinnati Knee Rating System, the Lysholm score, the Knee injury
      and Osteoarthritis Outcome Score, and the current health assessment form (SF-36)
      of the International Knee Documentation Committee, as well as histological
      analysis of second-look biopsies. Significant improvement (p < 0.05) in the
      evaluated scores was observed at 1 and/or 2 years after implantation of BioSeed
      C, and histological staining of the biopsies showed good integration of the graft
      and formation of a cartilaginous repair tissue. The Knee injury and
      Osteoarthritis Outcome Score showed significant improvement in the subclasses
      pain, other symptoms, and knee-related quality of life 2 years after implantation
      of BioSeed-C in focal osteoarthritic defects. The results suggest that implanting
      BioSeed-C is an effective treatment option for the regeneration of posttraumatic
      and/or osteoarthritic defects of the knee.

PMID- 17451598
TI  - N170 ERPs could represent a logographic processing strategy in visual word
      recognition.
AB  - BACKGROUND: Occipito-temporal N170 component represents the first step where
      face, object and word processing are discriminated along the ventral stream of
      the brain. N170 leftward asymmetry observed during reading has been often
      associated to prelexical orthographic visual word form activation. However, some
      studies reported a lexical frequency effect for this component particularly
      during word repetition that appears in contradiction with this prelexical
      orthographic step. Here, we tested the hypothesis that under word repetition
      condition, discrimination between words would be operated on visual rather than
      orthographic basis. In this case, N170 activity may correspond to a logographic
      processing where a word is processed as a whole. METHODS: To test such an
      assumption, frequent words, infrequent words and pseudowords were presented to
      the subjects that had to complete a visual lexical decision task. Different
      repetition conditions were defined 1--weak repetition, 2--massive repetition and
      3--massive repetition with font alternation. This last condition was designed to
      change visual word shape during repetition and therefore to interfere with a
      possible visual strategy during word recognition. RESULTS: Behavioral data showed
      an important frequency effect for the weak repetition condition, a lower but
      significant frequency effect for massive repetition, and no frequency effect for
      the changing font repetition. Moreover alternating font repetitions slowed
      subject's responses in comparison to "simple" massive repetition.ERPs results
      evidenced larger N170 amplitude in the left hemisphere for frequent than both
      infrequent words and pseudowords during massive repetition. Moreover, when words
      were repeated with different fonts this N170 effect was not present, suggesting a
      visual locus for such a N170 frequency effect. CONCLUSION: N170 represents an
      important step in visual word recognition, consisting probably in a prelexical
      orthographic processing. But during the reading of very frequent words or after a
      massive repetition of a word, it could represent a more holistic process where
      words are processed as a global visual pattern.

PMID- 17451599
TI  - Pragmatic trials in primary care. Methodological challenges and solutions
      demonstrated by the DIAMOND-study.
AB  - BACKGROUND: Pragmatic randomised controlled trials are often used in primary care
      to evaluate the effect of a treatment strategy. In these trials it is difficult
      to achieve both high internal validity and high generalisability. This article
      will discuss several methodological challenges in designing and conducting a
      pragmatic primary care based randomised controlled trial, based on our
      experiences in the DIAMOND-study and will discuss the rationale behind the
      choices we made. From the successes as well as the problems we experienced the
      quality of future pragmatic trials may benefit. DISCUSSION: The first challenge
      concerned choosing the clinically most relevant interventions to compare and
      enable blinded comparison, since two interventions had very different
      appearances. By adding treatment steps to one treatment arm and adding placebo to
      both treatment arms both internal and external validity were optimized.
      Nevertheless, although blinding is essential for a high internal validity, it
      should be warily considered in a pragmatic trial because it decreases external
      validity. Choosing and recruiting a representative selection of participants was
      the second challenge. We succeeded in retrieving a representative relatively
      large patient sample by carefully choosing (few) inclusion and exclusion
      criteria, by random selection, by paying much attention to participant
      recruitment and taking the participant's reasons to participate into account.
      Good and regular contact with the GPs and patients was to our opinion essential.
      The third challenge was to choose the primary outcome, which needed to reflect
      effectiveness of the treatment in every day practice. We also designed our
      protocol to follow every day practice as much as possible, although standardized
      treatment is usually preferred in trials. The aim of this was our fourth
      challenge: to limit the number of protocol deviations and increase external
      validity. SUMMARY: It is challenging to design and conduct a pragmatic trial.
      Thanks to thorough preparation, we were able to collect highly valid data. To our
      opinion, a critical deliberation of where on the pragmatic--explanatory spectrum
      you want your trial to be on forehand, in combination with consulting
      publications especially on patient recruitment procedures, has been helpful in
      conducting a successful trial.

PMID- 17451600
TI  - LEDGF/p75 has increased expression in blasts from chemotherapy-resistant human
      acute myelogenic leukemia patients and protects leukemia cells from apoptosis in
      vitro.
AB  - BACKGROUND: Relapse due to chemoresistant residual disease is a major cause of
      death in acute myelogenous leukemia (AML). The present study was undertaken to
      elucidate the molecular mechanisms of chemoresistance by comparing differential
      gene expression in blasts from patients with resistant relapsing AML and
      chemosensitive AML. RESULTS: About 20 genes were identified as preferentially
      expressed in blasts pooled from patients with resistant disease, as compared to
      chemosensitive AML blasts, based on differential gene expression screening. Half
      of these genes encoded proteins related to protein translation, of these a novel
      protein related to the ribosomal stalk protein P0. Other upregulated mRNAs coded
      for cytochrome C oxidase III, the transcription factors ERF-2/TIS11d, and the p75
      and p52 splice variants of Lens Epithelial Derived Growth Factor (LEDGF).
      Analysis of blasts from single patients disclosed that LEDGF/p75 was the most
      consistently upregulated mRNA in resistant AML. Transfection experiments
      demonstrated that LEDGF/p75 and p52b antagonized daunorubicin-induced and cAMP
      induced apoptosis in an AML cell line. Also HEK-293 cells were protected against
      daunorubicin by LEDGF/p75 and p52b, whereas LEDGF/p52 splice variants lacking
      exon 6 had proapoptotic effects. Interestingly, full length LEDGF/p75 protected
      against truncated pro-apoptotic LEDGF/p75. CONCLUSION: Our results provide
      evidence for an association between the overexpression of genes encoding survival
      proteins like LEDGF/p75 and chemo-resistance in acute myelogenous leukemia.
      LEDGF/p75 has previously not been shown to protect against chemotherapy, and is a
      potential drug target in AML.

PMID- 17451601
TI  - hnRNP E1 and E2 have distinct roles in modulating HIV-1 gene expression.
AB  - Pre-mRNA processing, including 5' end capping, splicing, and 3' end
      cleavage/polyadenylation, are events coordinated by transcription that can
      influence the subsequent export and translation of mRNAs. Coordination of RNA
      processing is crucial in retroviruses such as HIV-1, where inefficient splicing
      and the export of intron-containing RNAs are required for expression of the full
      complement of viral proteins. RNA processing can be affected by both viral and
      cellular proteins, and in this study we demonstrate that a member of the hnRNP E
      family of proteins can modulate HIV-1 RNA metabolism and expression. We show that
      hnRNP E1/E2 are able to interact with the ESS3a element of the bipartite ESS in
      tat/rev exon 3 of HIV-1 and that modulation of hnRNP E1 expression alters HIV-1
      structural protein synthesis. Overexpression of hnRNP E1 leads to a reduction in
      Rev, achieved in part through a decrease in rev mRNA levels. However, the
      reduction in Rev levels cannot fully account for the effect of hnRNP E1,
      suggesting that hmRNP E1 might also act to suppress viral RNA translation.
      Deletion mutagenesis determined that the C-terminal end of hnRNP E1 was required
      for the reduction in Rev expression and that replacing this portion of hnRNP E1
      with that of hnRNP E2, despite the high degree of conservation, could not rescue
      the loss of function.

PMID- 17451602
TI  - PPAR-alpha agonism improves whole body and muscle mitochondrial fat oxidation,
      but does not alter intracellular fat concentrations in burn trauma children in a
      randomized controlled trial.
AB  - BACKGROUND: Insulin resistance is often associated with increased levels of
      intracellular triglycerides, diacylglycerol and decreased fat beta-oxidation. It
      was unknown if this relationship was present in patients with acute insulin
      resistance induced by trauma. METHODS: A double blind placebo controlled trial
      was conducted in 18 children with severe burn injury. Metabolic studies to assess
      whole body palmitate oxidation and insulin sensitivity, muscle biopsies for
      mitochondrial palmitate oxidation, diacylglycerol, fatty acyl Co-A and fatty acyl
      carnitine concentrations, and magnetic resonance spectroscopy for muscle and
      liver triglycerides were compared before and after two weeks of placebo or PPAR
      alpha agonist treatment. RESULTS: Insulin sensitivity and basal whole body
      palmitate oxidation as measured with an isotope tracer increased significantly (P
      = 0.003 and P = 0.004, respectively) after PPAR-alpha agonist treatment compared
      to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased
      significantly after PPAR-alpha treatment (P = 0.002). However, the concentrations
      of muscle triglyceride, diacylglycerol, fatty acyl CoA, fatty acyl carnitine, and
      liver triglycerides did not change with either treatment. PKC-theta activation
      during hyper-insulinemia decreased significantly following PPAR-alpha treatment.
      CONCLUSION: PPAR-alpha agonist treatment increases palmitate oxidation and
      decreases PKC activity along with reduced insulin sensitivity in acute trauma,
      However, a direct link between these responses cannot be attributed to
      alterations in intracellular lipid concentrations.

PMID- 17451603
TI  - Development of the mammalian liver and ventral pancreas is dependent on GATA4.
AB  - BACKGROUND: In the mouse, the parenchyma of both the liver and ventral pancreas
      is specified from adjacent domains of the ventral foregut endoderm. GATA4, a zinc
      finger transcription factor, is strongly expressed in these endodermal domains
      and molecular analyses have implicated GATA4 in potentiating liver gene
      expression during the onset of hepatogenesis. We therefore hypothesized that
      GATA4 has an integral role in controlling the early stages of pancreatic and
      liver development. RESULTS: To determine whether GATA4 contributes to development
      of either the pancreas or liver we characterized the formation of pancreatic and
      hepatic tissues in embryos derived from Gata4-/- ES cells by tetraploid embryo
      complementation. In the absence of GATA4, development of the liver and ventral
      pancreas was disrupted. At embryonic day (E) 9.5, the liver bud failed to expand
      although, contrary to expectations, the hepatic endoderm was able to form a
      pseudo-stratified epithelial liver bud that expressed hepatic genes. Moreover, as
      we had shown previously, the embryos lacked septum transversum mesenchyme
      suggesting that liver defects may be cell non-autonomous. Analyses of pancreatic
      development revealed a complete absence of the ventral but not the dorsal
      pancreas in Gata4-/- embryos. Moreover, Gata6-/- embryos displayed a similar,
      although less dramatic phenotype, suggesting a critical role for multiple GATA
      factors at the earliest stages of ventral pancreas development. CONCLUSION: This
      study defines integral roles for GATA factors in controlling early development of
      the mammalian liver and pancreas.

PMID- 17451604
TI  - Amodiaquine failure associated with erythrocytic glutathione in Plasmodium
      falciparum malaria.
AB  - OBJECTIVE: To establish the relationship between production of glutathione and
      the therapeutic response to amodiaquine (AQ) monotherapy in Plasmodium falciparum
      non-complicated malaria patients. METHODOLOGY: Therapeutic response to AQ was
      evaluated in 32 patients with falciparum malaria in two townships of Antioquia,
      Colombia, and followed-up for 28 days. For every patient, total glutathione and
      enzymatic activity (glutathione reductase, GR, and gamma-glutamylcysteine
      synthetase, gamma-GCS) were determined in parasitized erythrocytes, non-infected
      erythrocytes and free parasites, on the starting day (day zero, before ingestion
      of AQ) and on the day of failure (in case of occurrence). RESULTS: There was
      found an AQ failure of 31.25%. Independent of the therapeutic response, on the
      starting day and on the day of failure, lower total glutathione concentration and
      higher GR activities in parasitized erythrocytes were found, compared with non
      infected erythrocytes (p < 0.003). In addition, only on the day of failure, gamma
      GCS activity of parasitized erythrocytes was higher, compared with that of
      healthy erythrocytes (p = 0.01). Parasitized and non-parasitized erythrocytes in
      therapeutic failure patients (TF) had higher total glutathione on the starting
      day compared with those of adequate clinical response (ACR) (p < 0.02).
      Parasitized erythrocytes of TF patients showed lower total glutathione on the
      failure day, compared with starting day (p = 0.017). No differences was seen in
      the GR and gamma-GCS activities by compartment, neither between the two
      therapeutic response groups nor between the two treatment days. CONCLUSION: This
      study is a first approach to explaining P. falciparum therapeutic failure in
      humans through differences in glutathione metabolism in TF and ACR patients.
      These results suggest a role for glutathione in the therapeutic failure to
      antimalarials.

PMID- 17451605
TI  - Case mix, outcome and activity for patients admitted to intensive care units
      requiring chronic renal dialysis: a secondary analysis of the ICNARC Case Mix
      Programme Database.
AB  - INTRODUCTION: This report describes the case mix, outcome and activity for
      admissions to intensive care units (ICUs) of patients who require prior chronic
      renal dialysis for end-stage renal failure (ESRF), and investigates the effect of
      case mix factors on outcome. METHODS: This was a secondary analysis of a high
      quality clinical database, namely the Intensive Care National Audit & Research
      Centre (ICNARC) Case Mix Programme Database, which includes 276,731 admissions to
      170 adult ICUs across England, Wales and Northern Ireland from 1995 to 2004.
      RESULTS: During the eight year study period, 1.3% (n = 3,420) of all patients
      admitted to ICU were receiving chronic renal dialysis before ICU admission. This
      represents an estimated ICU utilization of six admissions (32 bed-days) per 100
      dialysis patient-years. The ESRF group was younger (mean age 57.3 years versus
      59.5 years) and more likely to be male (60.2% versus 57.9%) than those without
      ESRF. Acute Physiology and Chronic Health Evaluation II score and Acute
      Physiology Score revealed greater severity of illness on admission in patients
      with ESRF (mean 24.7 versus 16.6 and 17.2 versus 12.6, respectively). Length of
      stay in ICU was comparable between groups (median 1.9 days versus 1.8 days) and
      ICU mortality was only slightly elevated in the ESRF group (26.3% versus 20.8%).
      However, the ESRF group had protracted overall hospital stay (median 25 days
      versus 17 days), and increased hospital mortality (45.3% versus 31.2%) and ICU
      readmission (9.0% vs. 4.7%). Multiple logistic regression analysis adjusted for
      case mix identified the increased hospital mortality to be associated with
      increasing age, emergency surgery and nonsurgical cases, cardiopulmonary
      resuscitation before ICU admission and extremes of physiological norms. The
      adjusted odds ratio for ultimate hospital mortality associated with chronic renal
      dialysis was 1.24 (95% confidence interval 1.13 to 1.37). CONCLUSION: Patients
      with ESRF admitted to UK ICUs are more likely to be male and younger, with a
      medical cause of admission, and to have greater severity of illness than the non
      ESRF population. Outcomes on the ICU were comparable between the two groups, but
      those patients with ESRF had greater readmission rates, prolonged post-ICU
      hospital stay and increased post-ICU hospital mortality. This study is by far the
      largest comparative outcome analysis to date in patients with ESRF admitted to
      the ICU. It may help to inform clinical decision-making and resource requirements
      for this patient population.

PMID- 17451606
TI  - Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL/T
      helper peptides in VacciMax.
AB  - BACKGROUND: Melanoma tumors are known to express antigens that usually induce
      weak immune responses of short duration. Expression of both tumor-associated
      antigens p53 and TRP2 by melanoma cells raises the possibility of simultaneously
      targeting more than one antigen in a therapeutic vaccine. In this report, we show
      that VacciMax (VM), a novel liposome-based vaccine delivery platform, can
      increase the immunogenicity of melanoma associated antigens, resulting in tumor
      elimination. METHODS: C57BL/6 mice bearing B16-F10 melanoma tumors were
      vaccinated subcutaneously 6 days post tumor implantation with a mixture of
      synthetic peptides (modified p53: 232-240, TRP-2: 181-188 and PADRE) and CpG.
      Tumor growth was monitored and antigen-specific splenocyte responses were assayed
      by ELISPOT. RESULTS: Vaccine formulated in VM increased the number of both TRP2-
      and p53-specific IFN-gamma producing splenocytes following a single vaccination.
      Vaccine formulated without VM resulted only in enhanced IFN-gamma producing
      splenocytes to one CTL epitopes (TRP2:180-188), suggesting that VM overcomes
      antigen dominance and enhances immunogenicity of multiple epitopes. Vaccination
      of mice bearing 6-day old B16-F10 tumors with both TRP2 and p53-peptides
      formulated in VM successfully eradicated tumors in all mice. A control vaccine
      which contained all ingredients except liposomes resulted in eradication of
      tumors in no more than 20% of mice. CONCLUSION: A single administration of VM is
      capable of inducing an effective CTL response to multiple tumor-associated
      antigens. The responses generated were able to reject 6-day old B16-F10 tumors.

PMID- 17451607
TI  - Supervised multivariate analysis of sequence groups to identify specificity
      determining residues.
AB  - BACKGROUND: Proteins that evolve from a common ancestor can change functionality
      over time, and it is important to be able identify residues that cause this
      change. In this paper we show how a supervised multivariate statistical method,
      Between Group Analysis (BGA), can be used to identify these residues from
      families of proteins with different substrate specifities using multiple sequence
      alignments. RESULTS: We demonstrate the usefulness of this method on three
      different test cases. Two of these test cases, the Lactate/Malate dehydrogenase
      family and Nucleotidyl Cyclases, consist of two functional groups. The other
      family, Serine Proteases consists of three groups. BGA was used to analyse and
      visualise these three families using two different encoding schemes for the amino
      acids. CONCLUSION: This overall combination of methods in this paper is powerful
      and flexible while being computationally very fast and simple. BGA is especially
      useful because it can be used to analyse any number of functional classes. In the
      examples we used in this paper, we have only used 2 or 3 classes for
      demonstration purposes but any number can be used and visualised.

PMID- 17451608
TI  - Transcription-related mutations and GC content drive variation in nucleotide
      substitution rates across the genomes of Arabidopsis thaliana and Arabidopsis
      lyrata.
AB  - BACKGROUND: There has been remarkably little study of nucleotide substitution
      rate variation among plant nuclear genes, in part because orthology is difficult
      to establish. Orthology is even more problematic for intergenic regions of plant
      nuclear genomes, because plant genomes generally harbor a wealth of repetitive
      DNA. In theory orthologous intergenic data is valuable for studying rate
      variation because nucleotide substitutions in these regions should be under
      little selective constraint compared to coding regions. As a result, evolutionary
      rates in intergenic regions may more accurately reflect genomic features, like
      recombination and GC content, that contribute to nucleotide substitution.
      RESULTS: We generated a set of 66 intergenic sequences in Arabidopsis lyrata, a
      close relative of Arabidopsis thaliana. The intergenic regions included
      transposable element (TE) remnants and regions flanking the TEs. We verified
      orthology of these amplified regions both by comparison of existing A. lyrata--A.
      thaliana genetic maps and by using molecular features. We compared substitution
      rates among the 66 intergenic loci, which exhibit ~5-fold rate variation, and
      compared intergenic rates to a set of 64 orthologous coding sequences. Our chief
      observations were that the average rate of nucleotide substitution is slower in
      intergenic regions than in synonymous sites, that rate variation in both
      intergenic and coding regions correlate with GC content, that GC content alone is
      not sufficient to explain differences in rates between intergenic and coding
      regions, and that rates of evolution in intergenic regions correlate negatively
      with gene density. CONCLUSION: Our observations indicated that mutation rates
      vary among genomics regions as a function of base composition, suggesting that
      previous observations of "selective constraint" on non-coding regions could more
      accurately be attributed to a GC effect instead of selection. The negative
      correlation between nucleotide substitution rate and gene density provides a
      potential neutral explanation for a previously documented correlation between
      gene density and polymorphism levels within A. thaliana. Finally, we discuss
      potential forces that could contribute to rapid synonymous rates, and provide
      evidence to suggest that transcription-related mutation contributes to rate
      differences between intergenic and synonymous sites.

PMID- 17451609
TI  - An adaptive bin framework search method for a beta-sheet protein homopolymer
      model.
AB  - BACKGROUND: The problem of protein structure prediction consists of predicting
      the functional or native structure of a protein given its linear sequence of
      amino acids. This problem has played a prominent role in the fields of
      biomolecular physics and algorithm design for over 50 years. Additionally, its
      importance increases continually as a result of an exponential growth over time
      in the number of known protein sequences in contrast to a linear increase in the
      number of determined structures. Our work focuses on the problem of searching an
      exponentially large space of possible conformations as efficiently as possible,
      with the goal of finding a global optimum with respect to a given energy
      function. This problem plays an important role in the analysis of systems with
      complex search landscapes, and particularly in the context of ab initio protein
      structure prediction. RESULTS: In this work, we introduce a novel approach for
      solving this conformation search problem based on the use of a bin framework for
      adaptively storing and retrieving promising locally optimal solutions. Our
      approach provides a rich and general framework within which a broad range of
      adaptive or reactive search strategies can be realized. Here, we introduce
      adaptive mechanisms for choosing which conformations should be stored, based on
      the set of conformations already stored in memory, and for biasing choices when
      retrieving conformations from memory in order to overcome search stagnation.
      CONCLUSION: We show that our bin framework combined with a widely used
      optimization method, Monte Carlo search, achieves significantly better
      performance than state-of-the-art generalized ensemble methods for a well-known
      protein-like homopolymer model on the face-centered cubic lattice.

PMID- 17451610
TI  - Spectral estimation in unevenly sampled space of periodically expressed
      microarray time series data.
AB  - BACKGROUND: Periodogram analysis of time-series is widespread in biology. A new
      challenge for analyzing the microarray time series data is to identify genes that
      are periodically expressed. Such challenge occurs due to the fact that the
      observed time series usually exhibit non-idealities, such as noise, short length,
      and unevenly sampled time points. Most methods used in the literature operate on
      evenly sampled time series and are not suitable for unevenly sampled time series.
      RESULTS: For evenly sampled data, methods based on the classical Fourier
      periodogram are often used to detect periodically expressed gene. Recently, the
      Lomb-Scargle algorithm has been applied to unevenly sampled gene expression data
      for spectral estimation. However, since the Lomb-Scargle method assumes that
      there is a single stationary sinusoid wave with infinite support, it introduces
      spurious periodic components in the periodogram for data with a finite length. In
      this paper, we propose a new spectral estimation algorithm for unevenly sampled
      gene expression data. The new method is based on signal reconstruction in a shift
      invariant signal space, where a direct spectral estimation procedure is developed
      using the B-spline basis. Experiments on simulated noisy gene expression profiles
      show that our algorithm is superior to the Lomb-Scargle algorithm and the
      classical Fourier periodogram based method in detecting periodically expressed
      genes. We have applied our algorithm to the Plasmodium falciparum and Yeast gene
      expression data and the results show that the algorithm is able to detect
      biologically meaningful periodically expressed genes. CONCLUSION: We have
      proposed an effective method for identifying periodic genes in unevenly sampled
      space of microarray time series gene expression data. The method can also be used
      as an effective tool for gene expression time series interpolation or resampling.

PMID- 17451611
TI  - Treatment of patients with Eisenmenger's syndrome with Bosentan.
AB  - We treated prospectively 14 patients with Eisenmenger's syndrome, with a mean age
      of 10 years, ranging from 3 to 18 years. Treatment continued for 12 months, and
      demonstrated a lasting symptomatic improvement, but no improvement in terms of
      mean saturation of oxygen over 24 hours. Exercise capacity, as judged by peak
      uptake of oxygen, worsened in the six patients able to perform a treadmill test.
      The symptomatic benefit from dual blockage of endothelin receptors in these
      patients may be due to mechanisms other than selective pulmonary vasodilatation
      alone.

PMID- 17451612
TI  - Tinnitus rehabilitation: a mindfulness meditation cognitive behavioural therapy
      approach.
AB  - BACKGROUND: Chronic tinnitus is a frequent symptom presentation in clinical
      practice. No drug treatment to date has shown itself to be effective. The aim of
      the present study was to investigate the effects of cognitive behavioural therapy
      and meditation in tinnitus sufferers. METHODOLOGY: Patients were selected from a
      dedicated tinnitus clinic in the Welsh Hearing Institute. A waiting list control
      design was used. Twenty-five chronic tinnitus sufferers were consecutively
      allocated to two groups, one receiving a cognitive behavioural therapy/meditation
      intervention of four one hour sessions with the other group waiting three months
      and subsequently treated in the same way, thereby acting as their own control.
      The main outcome was measured using the Hallam tinnitus questionnaire. A four to
      six month follow up was conducted. RESULTS: These showed significant statistical
      reductions in tinnitus variables both in the active and also in the control
      group. Post-therapy, no significant change was found after the waiting list
      period. The improvement was maintained at the four to six month period.
      CONCLUSION: The positive findings give support for the use of cognitive
      behavioural therapy/meditation for chronic tinnitus sufferers.

PMID- 17451613
TI  - Effects of long-term intervention with low- and high-glycaemic-index breakfasts
      on food intake in children aged 8-11 years.
AB  - The aim of the present study was to investigate the effects of long-term
      intervention of low-glycaemic-index (GI) v. high-GI breakfasts on energy and
      macronutrient intakes in children aged 8-11 years. Preadolescent children were
      assigned to one of two groups in a random cross-over design. Each group was given
      low-GI and high-GI breakfasts on two non-consecutive days per week for 10 weeks
      per breakfast type. Each breakfast provided approximately 1273 kJ (300 kcal) and
      was closely matched for macronutrient and dietary fibre content. Subsequent food
      intake at an ad libitum buffet lunch was recorded and daily energy and
      macronutrient intakes were measured by 24 h recall and 3 d food diaries. There
      was a tendency towards a reduced energy intake at lunch following the low-GI
      breakfast compared with the high-GI breakfast, although the mean difference of 75
      kJ (18 kcal) was not significant (P = 0.406). In particular, there was a trend
      towards a reduced energy intake in the low-GI arm compared with the high-GI arm
      among boys. In addition, data from the 3 d food diaries showed that there was a
      tendency towards a reduced energy intake during the low-GI compared with the high
      GI study period. In conclusion, although the difference in energy intake
      following the low-GI and high-GI breakfasts was not statistically significant,
      the reduced energy intake following the low-GI breakfast is encouraging. Both
      dietary fibre and carbohydrate type may affect GI, thus their potential and
      relative modulating effect on appetite requires further investigation.

PMID- 17451614
TI  - Potential ethnic modifiers in the assessment and treatment of Alzheimer's
      disease: challenges for the future.
AB  - OBJECTIVE: Despite numerous clinical trials, it is unknown whether ethnicity
      affects treatment response to cognitive enhancers in Alzheimer's disease (AD).
      There is convincing evidence of ethnic and genetic variability in drug
      metabolism. This article reviews the available data on ethnicity in clinical
      trials for AD to answer two questions: (1) what are the challenges to diagnose
      and treat AD across different ethnic groups, and (2) are there differences in
      response to pharmacologic interventions for AD across these different ethnic
      groups? METHOD: Available data from Alzheimer's Disease Cooperative Study (ADCS)
      randomized controlled clinical trials and from randomized controlled industry
      sponsored trials for four cognitive enhancers (donepezil, galantamine,
      rivastigmine and sabeluzole) were pooled to assess the numbers of non-Caucasian
      participants. RESULTS: The participation of ethnic minority subjects in clinical
      trials for AD was dependent on the funding source, although Caucasian
      participants were over-represented and non-Caucasian participants were under
      represented in the clinical trials. Because of the low participation rate of
      ethnic minorities, there were insufficient data to assess any differences in
      treatment outcome among different ethnic groups. Strategies to improve diversity
      in clinical trials are discussed. CONCLUSION: Greater participation of ethnically
      diverse participants in clinical trials for AD would generate additional
      information on possible differences in metabolism, treatment response, adverse
      events to therapeutic agents, and could foster the investigation of genetic
      variability among ethnic groups.

PMID- 17451615
TI  - Evaluating the uses of the total score and the domain scores in the Cognitive
      Abilities Screening Instrument, Chinese version (CASI C-2.0): results of
      confirmatory factor analysis.
AB  - BACKGROUND: The Cognitive Abilities Screening Instrument (CASI) consists of items
      which are designed to measure the nine domains of cognitive ability. Its total
      score is used clinically to represent the overall underlying cognitive ability of
      the patient. This study aimed to evaluate the justification of the uses of the
      all-domain-total-score as an overall cognitive measure and the domain scores as
      measures of designated individual cognitive ability. METHODS: To justify the use
      of total score of all the items as an overall measure of cognitive ability, a
      second-order confirmatory factor analysis was performed to examine whether the
      items in CASI contributed significantly to a common underlying construct. The
      uses of domain scores were also examined by inspecting the loadings of the items
      on their designated domains. The CASI data from 608 patients, 68 normal and 540
      with Alzheimer's disease, were analyzed. RESULTS: The goodness-of-fit indices for
      the second-order factor model were as follows: CFI was 0.912 for WLSMV and 0.977
      for WLSM; TLI and RMSEA values were 0.975 and 0.090 respectively. The loadings of
      the items on the common underlying construct are all salient (>0.3). The loadings
      of all but the long-term memory items on their respective subdomains were also
      salient. CONCLUSIONS: The items of the CASI C-2.0 were useful not only in
      profiling the correlated cognitive domain scores, but also in forming an overall
      measure of the underlying cognitive ability of the patients.

PMID- 17451616
TI  - Treatment of depression in low-level residential care facilities for the elderly.
AB  - BACKGROUND: The rate of recognition and treatment of depressed older people in
      nursing homes is low. Data from the low-level residential care population have
      not been reported. This study aimed to collect information about the treatment of
      depression among older persons living in low-level residential care (hostels).
      METHOD: The participants comprised 300 elderly residents from ten low-level
      residential care facilities from various suburbs in metropolitan Melbourne. The
      participants were interviewed by a trained clinical psychologist to determine the
      presence or absence of major or minor depressive disorder using the Structured
      Clinical Interview for DSM-IV Axis I Disorder (SCID-I). Each participant was also
      administered the Standardized Mini-mental State Examination (SMMSE) to determine
      level of cognitive function. The clinical psychologist then reviewed all cases in
      consultation with a geropsychiatrist experienced in the diagnosis of depression
      among older people, prior to assigning a diagnosis of depression. RESULTS: An
      important finding in this study was the low treatment for currently depressed
      residents, with less than half of those in the sample who were depressed
      receiving treatment. However, 61 of the 96 residents out of the sample of 300 who
      were on antidepressants were not currently depressed. CONCLUSION: There is an
      under recognition and under treatment of currently depressed older people in low
      level residential care facilities (hostels) just as has been reported in studies
      in nursing homes. However, there are high numbers receiving antidepressants who
      are not currently depressed.

PMID- 17451617
TI  - Self-stigma, self-esteem and age in persons with schizophrenia.
AB  - BACKGROUND: The relationship between self-stigma and self-esteem in patients with
      schizophrenia is receiving increased attention. However, studies to date have
      been limited to samples of persons under the age of 65. AIM: To examine the
      relationship between self-stigma and self-esteem in people with schizophrenia in
      both younger and older age groups. METHODS: Face-to-face interviews were
      completed with 86 inpatients with schizophrenia in a psychiatric hospital (mean
      age = 54, 55% female). Self-esteem was assessed using Rosenberg's Self Esteem
      Scale. Self-stigma was assessed using an adapted version of the Internalized
      Stigma of Mental Health (ISMI) scale. Information regarding socio-demographic
      characteristics and psychiatric history and symptomatology was collected.
      RESULTS: Self-stigma was moderate with only 20-33% of the participants reporting
      high levels of stigmatization. Older participants reported lower levels of self
      stigma than younger participants. A relatively strong association between self
      stigma and self-esteem was found. CONCLUSIONS: The findings point to the
      complexity of the association between self-stigma, self-esteem and age in people
      with schizophrenia. This study stresses the importance of clinicians taking the
      issue of self-stigma into consideration when treating young and old patients with
      schizophrenia.

PMID- 17451619
TI  - A comprehensive analysis of the biogeography of the thelastomatoid pinworms from
      Australian burrowing cockroaches (Blaberidae: Geoscapheinae, Panesthiinae): no
      evidence of coevolution.
AB  - We report 21 thelastomatoid species parasitizing 31 described and 5 undescribed
      geoscapheine and panesthiine cockroaches, representing all but 1 of the known
      species of these subfamilies in Australia. The nematodes have 3 distinct patterns
      of host distribution: dominant, moderate and rare. The 4 dominant species,
      Cordonicola gibsoni, Leidynemella fusiformis, Travassosinema jaidenae and
      Aoruroides queenslandensis, are highly prevalent, found in nearly all host
      species examined, and broadly distributed. The 8 moderate species have lower
      prevalences but are still widely distributed. Many of these species are more
      common in one host subfamily than the other. The remaining 9 rare species have
      highly restricted host and geographical distributions. Six of the 21 species are
      exclusive to geoscapheines, 5 to panesthiines and 10 are shared. These patterns
      suggest that most of the reported thelastomatoid species are generalists rather
      than specialists, that host-specificity within this group is low and that co
      evolutionary speciation has had little, if any, impact on structuring the
      thelastomatoid fauna of Australian burrowing cockroaches. In a broader context,
      this study provides the first comprehensive examination of the role of
      coevolutionary speciation and host specificity in regulating the distribution of
      pinworms in arthropods.

PMID- 17451618
TI  - Genistein from Flemingia vestita (Fabaceae) enhances NO and its mediator (cGMP)
      production in a cestode parasite, Raillietina echinobothrida.
AB  - Cyclic GMP (cGMP) is responsible for various cellular functions including signal
      pathways and it acts as a mediator for nitric oxide (NO). In order to evaluate
      the anthelmintic efficacy of the plant-derived isoflavones, the crude peel
      extract of Flemingia vestita and pure genistein were tested with respect to the
      activity of nitric oxide synthase (NOS), NO efflux and the cGMP concentration in
      Rallietina echinobothrida, the cestode parasite of domestic fowl. For comparison,
      the parasites were also treated with genistein (the major isoflavone present in
      the crude peel extract), sodium nitroprusside (SNP), a known NO donor, and
      praziquantel (PZQ), the reference drug. At the time of onset of paralysis in the
      parasite, the activity of NOS showed a significant increase (35-46%) and a 2-fold
      increase of NO efflux into the incubation medium in the treated worms in
      comparison to the respective controls. The cGMP concentration in the parasite
      tissue increased by 46-84% in the treated test worms in comparison to the
      controls. The results show that the isoflavones, genistein in particular, from
      the crude peel extract of F. vestita influence the cGMP concentration in the
      parasite tissue, which plays a major role in the downstream signal pathways.

PMID- 17451620
TI  - The impact of dietary cation anion difference (DCAD) on the acid-base balance and
      calcium metabolism of non-lactating, non-pregnant dairy cows fed equal amounts of
      different anionic salts.
AB  - We evaluated the impact of the dietary cation-anion difference (DCAD) on the
      influence of anionic salts (AS) on the metabolism of dairy cows using a study
      design that included control of feed intake. Ten mature, non-lactating, non
      pregnant, Holstein-Friesian-crossbreed cows received 2000 mEq of either one of
      the seven anionic salts tested, two combinations of the anionic salts or water as
      control via a rumen cannula. Salts and controls were assigned in a 10x10 Latin
      square design. Whole blood, serum and urine samples were taken during treatment
      (TP) and washout period. Samples of whole blood were tested for pH, base-excess
      and bicarbonate concentrations. In urine, pH and net acid-base excretion (NABE)
      were analysed. Calcium was measured in serum and urine. According to the
      different batches of hay, five groups of DCAD were created regarding cluster
      analysis. Changes in urine and blood parameters were statistically analysed for
      each DCAD group separately. The different DCAD had an impact on the amount of
      change in acid-base balance (ABB) and calcium metabolism and for how long these
      changes lasted. In the DCAD group receiving the highest amount of AS (239 mEq/kg
      dry matter with AS), changes of ABB were only noticeable in urine and these
      changes only differed from day zero in the first week of TP (P<0.05). In the
      other four groups changes of ABB were also visible in blood parameters, but only
      on a few days of TP did the deviations differ significantly (P<0.05) from day
      zero. Changes of ABB parameters in urine samples were more pronounced than those
      in blood and differed clearly from day zero (P<0.05). Parallel to the changes of
      ABB, calcium concentrations in these samples were significantly increased
      (P<0.001) in all DCAD groups. Except for the highest DCAD group, ionized calcium
      concentrations changed over time (P<0.020). However, the differences were very
      small and only differed from day zero on a few TP days. We conclude that the DCAD
      of a dairy cow's diet has an important impact on the effect of AS on ABB and
      calcium metabolism with respect to the duration and amount of change. The target
      regions of DCAD should be clearly below 100 mEq/kg dry matter to ensure the
      desired effect on ABB and calcium metabolism. Extremely negative DCAD should be
      avoided to minimize the risk of clinical acidosis induced by AS.

PMID- 17451621
TI  - Characterization of the antibody isotype response in serum and milk of heifers
      vaccinated with a Staphylococcus aureus bacterin (Lysigin).
AB  - The objective was to characterize the antibody isotype responses to vaccination
      with a commercial Staphylococcus aureus bacterin in dairy heifers. Twenty-five
      Holstein-Friesian dairy heifers were assigned at random to one of two groups,
      vaccinates (n=14) or controls (n=11). Vaccinates received two 5-ml doses of
      Lysigin 28 d apart in late gestation. Both groups were challenged with a
      heterologous serotype 5 strain of Staph. aureus by aseptic intramammary infusion
      on days 6, 7 and 8 of lactation. Samples for serum antibody isotype (IgG, IgG1,
      IgG2 and IgM) determinations were taken before each vaccination, immediately
      prior to challenge (6 d post-calving) and at the end of the study (28 d post
      calving). Samples for milk antibody isotype determinations were taken immediately
      prior to challenge and at the end of the study. Antibody isotype sample-to
      positive ratios (S:P ratio=(mean test sample OD-mean within-plate negative
      control OD)/(mean within-plate positive control OD-mean within-plate negative
      control OD)) were determined in milk and serum using a series of ELISAs coated
      with different strains of Staph. aureus belonging to capsular polysaccharide (CP)
      serotype 5 or 8 or surface polysaccharide (SP) serotype 336. Vaccinates had
      higher mean serum IgG1 and IgG2 S:P ratios than controls against all three
      strains of Staph. aureus (P < or = 0.023). Vaccinates had higher mean milk IgG
      S:P ratios than controls against CP8 and SP336 strains of Staph. aureus (P< or =
      0.030). Hence, a humoural immune response to the vaccine was detected in serum
      and milk, but responses varied according to strain and antibody isotype tested.

PMID- 17451622
TI  - Dairy cow cleanliness and milk quality on organic and conventional farms in the
      UK.
AB  - A subjective cow cleanliness scoring system was validated and used to assess the
      cleanliness score of dairy cows at different times in the year. A longitudinal
      study followed a number of farms from summer to winter, and a larger, cross
      sectional study assessed a greater number of farms during the housed winter
      period. The scoring system was demonstrated to be both a repeatable and practical
      technique to use on-farm and showed that cows become dirtier in the transition
      from summer grazing to winter housing. Although farming system (organic or
      conventional) had no effect on cow cleanliness when cows were at grass, when
      housed in the winter, organic cows were significantly more likely to be cleaner.
      There was a link between cow cleanliness scores and milk quality, with herds
      having lower bulk tank somatic cell counts (BTSCC) tending to have a lower
      (cleaner) median cow cleanliness score; with this relationship strongest for the
      organic herds. There was no significant link between cleanliness score and
      Bactoscan (BS) count or clinical mastitis incidence. No major mastitis pathogens
      were cultured from bulk tank milk samples from the quartile of herds with the
      cleanest cows in contrast to the quartile of herds with the dirtiest cows, where
      significant mastitis pathogens were cultured. Based on this study, all farms,
      especially organic systems, should attempt to keep cows clean as part of
      subclinical mastitis control.

PMID- 17451623
TI  - Differences in susceptibility to Mannheimia haemolytica-associated mastitis
      between two breeds of dairy sheep.
AB  - We used a Mannheimia haemolytica isolate to study differences in susceptibility
      to experimental mastitis between two breeds of dairy sheep. The isolate was
      deposited into the teat duct of Karagouniko (K, n=8) or Frisarta (F, n=8) ewes.
      The animals were monitored by means of clinical, bacteriological, cytological and
      pathological methods. K ewes did not develop any systemic or mammary clinical
      signs, whilst F ewes became ill and developed acute clinical mastitis 12 h later
      (P<0.001). Bacteria were isolated from 34/48 samples from K ewes and from 46/46
      samples from F ewes. Positive California mastitis test (CMT) results were 17/24
      samples from K ewes and 23/23 samples from F ewes; leucocytes were seen in Giemsa
      stained films. Total pathology score summed over all group K ewes was 41 (maximum
      possible: 128); Man. haemolytica was isolated from 12/24 tissue samples. Total
      pathology score summed over all group F ewes was 93; Man. haemolytica was
      isolated from 24/24 tissue samples. Hyperplastic lymphoid nodules consisting of
      lymphocytes and plasma cells with germinal activity were characteristically
      present at the border between teat duct-teat cistern of group K ewes; no such
      structures were observed in teats of group F ewes. The results identified
      differences in susceptibility/resistance to a mastitis pathogen among animals of
      the two breeds. Defence mechanisms of the teat appeared to be inadequate against
      the invading organisms; as lymphoid nodules have been considered important
      defensive mechanisms of the ovine teat, their observed lack in Frisarta ewes
      might have predisposed them to development of mastitis.

PMID- 17451624
TI  - Lactation induction as a predictor of post-parturition transgene expression in
      bovine milk.
AB  - The bovine's long generation interval results in a delay of several years when
      evaluating mammary specific transgenes in genetically engineered animals. This
      experiment was conducted to evaluate the feasibility of reducing that waiting
      period. Lactation was induced in prepubertal bull and heifer calves as a means of
      predicting transgene behaviour during subsequent post-parturient lactations in
      the heifers themselves, and in daughters sired by the bulls. The animals carry a
      lactation-specific transgene encoding lysostaphin, an antimicrobial protein that
      kills Staphlococcus aureus, a mastitis-causing pathogen. Oestrogen, progesterone
      and dexamethasone were administered as previously described (Ball et al. 2000) to
      nine heifers (five transgenics) ranging in weight from 80 to 145 kg. Eight bull
      calves (seven transgenics) weighing 81-178 kg received additional oestrogen and
      progesterone injection prior to dexamethasone treatment. All nine heifers
      responded to the milk induction scheme yielding between 19 ml and 4.5 l over 5 d.
      Milk volume from the four responding males (30 microl to 2.5 ml) was
      significantly less than that harvested from females (P=0.025). Only bull calves
      >117 kg had a positive response. Lysostaphin was detected in all transgenic
      prepubertal heifers and in two transgenic prepubertal bull calves induced. A
      positive relationship was observed between lysostaphin's stapholytic activity in
      the two types of lactations (r2=0.907, P<0.001) thus providing a useful means of
      predicting subsequent lysostaphin production in post-partum milk.

PMID- 17451625
TI  - Effect of intramammary infection in Bergamasca meat sheep on milk parameters and
      lamb growth.
AB  - Pooled milk samples from 115 Bergamasca meat sheep were collected aseptically
      five times from lambing to weaning to determine the prevalence of intramammary
      infection, somatic cell counts and milk quality parameters (protein, fat and
      lactose), and effects of infection on lamb weight gain. The global prevalence of
      subclinical intramammary infection was 51.2%. The Staphylococcus genus was
      responsible for the greatest prevalence (53.3% among infected udders).
      Staphylococcus aureus was isolated in 8.4% of infected milk samples. Infection
      status had significant effects on fat and protein percentage and on somatic cell
      count. Lamb growth was greatest for lambs of ewes with no infection and decreased
      as the number of infected samples increased. No significant differences were
      detected in the growth of lambs with dams infected by different bacterial
      species.

PMID- 17451626
TI  - Evidence of dissociative amnesia.

PMID- 17451627
TI  - Predictors, clinical characteristics, and outcome of conduct disorder in girls
      with attention-deficit/hyperactivity disorder: a longitudinal study.
AB  - BACKGROUND: Research on the overlap between attention-deficit/hyperactivity
      disorder (ADHD) and conduct disorder (CD) in males has provided useful
      information on the etiology, correlates, course, and nosology of this co-morbid
      condition. However, it is unclear how these results extend to females. Our aim
      was to examine the predictors, clinical characteristics, and functional outcome
      of CD in a sample of female youth with and without ADHD. METHOD: We conducted a
      blind, 5-year prospective longitudinal study of girls with (n=140) and without
      (n=122) ADHD, aged 6-18 years at baseline. At the 5-year follow-up, 123 (88%) and
      112 (92%) of the ADHD and control children respectively were reassessed at a mean
      age of 16.7 years. Psychiatric disorders were assessed using blind structured
      diagnostic interviews. RESULTS: Baseline ADHD was a significant risk factor for
      lifetime CD throughout childhood and adolescence [hazard ratio (HR) 5.8, 95%
      confidence interval (CI) 2.9-11.5, p<0.001]. Among ADHD girls, childhood-onset
      (<12 years) CD was predicted by paternal antisocial personality disorder (ASPD),
      while adolescent-onset CD (12 years) was predicted by family conflict. In
      addition, lifetime CD significantly predicted academic, psychiatric and sexual
      behavior problems in girls with ADHD at follow-up. CONCLUSIONS: ADHD is a
      significant risk factor for CD in girls. CD is associated with increased risk for
      academic, psychiatric and sexual behavior problems compared to ADHD girls without
      CD. Given that the therapeutic approaches indicated by ADHD and CD differ, these
      findings highlight the importance of improved efforts aimed at early
      identification and treatment of CD in girls with ADHD.

PMID- 17451628
TI  - Mild cognitive impairment as predictor for Alzheimer's disease in clinical
      practice: effect of age and diagnostic criteria.
AB  - BACKGROUND: We investigated whether the predictive accuracy of mild cognitive
      impairment (MCI) for Alzheimer-type dementia (AD) in a clinical setting is
      dependent on age and the definition of MCI used. METHOD: Non-demented subjects
      older than 40 (n=320) who attended a memory clinic of a university hospital were
      reassessed 5 years later for the presence of AD. MCI was diagnosed according to
      the criteria of amnestic MCI, mild functional impairment (MFI), ageing-associated
      cognitive decline (AACD), and age-associated memory impairment (AAMI). The main
      outcome measure was the area under the curve (AUC) of a receiver operating
      characteristic (ROC) curve. Analyses were conducted on the entire sample and on
      subgroups of subjects aged 40-54, 55-69 and 70-85 years. RESULTS: A diagnosis of
      AD at follow-up was made in 58 subjects. Four of them were in the 40-54 age
      group, 29 in the 55-69 age group and 25 in the 70-85 age group. The diagnostic
      accuracy in the entire sample was low to moderately high with AUCs ranging from
      0.56 (AACD) to 0.75 (amnestic MCI). A good predictive accuracy with an AUC >0.80
      was only observed in subjects aged 70-85 using the criteria of amnestic MCI
      (AUC=0.84). CONCLUSIONS: The predictive accuracy of MCI for AD is dependent on
      age and the definition of MCI used. The predictive accuracy is good only for
      amnestic MCI in subjects 70-85 years. As subjects with prodromal AD are often
      younger than 70, the usefulness of MCI as predictor of AD in clinical practice is
      limited.

PMID- 17451629
TI  - Estrogen, menstrual cycle phases, and psychopathology in women suffering from
      schizophrenia.
AB  - BACKGROUND: Estrogen has been hypothesized to have a protective and antipsychotic
      like effect in women at risk for schizophrenia. The aim of the present study was
      to evaluate the association between menstrual cycle and/or estrogen levels and
      psychotic symptoms in a sample of women with schizophrenia. METHOD: One hundred
      and twenty-five premenopausal women with schizophrenia and regular menses were
      examined. The levels of 17beta-estradiol and other hormones of the gonadal axis
      were assessed in the follicular, peri-ovulatory, and luteal phases of the
      menstrual cycle. The effects of the menstrual cycle phase and/or the estradiol
      level on the Positive and Negative Syndrome Scale (PANSS) and the Brief
      Psychiatric Rating Scale (BPRS) scores were calculated by means of regression
      analyses. RESULTS: Significant improvement in psychotic, but not depressive,
      symptoms was observed during the luteal phase, compared with other days of the
      menstrual cycle. CONCLUSIONS: The present findings indicate that estradiol may
      have specific antipsychotic-like effects on the symptoms of schizophrenia. Thus
      further investigation into the therapeutic effect of estrogen may be worthwhile.

PMID- 17451630
TI  - Inhibitory deficits for negative information in persons with major depressive
      disorder.
AB  - BACKGROUND: Within Beck's cognitive model of depression, little is known about
      the mechanism(s) by which activated self-schemas result in the production of
      negative thoughts. Recent research has demonstrated that inhibitory dysfunction
      is present in depression, and this deficit is likely valence-specific. However,
      whether valence-specific inhibitory deficits are associated with increased
      negative cognition and whether such deficits are specific to depression per se
      remains unexamined. The authors posit the theory that inhibitory dysfunction may
      influence the degree to which activated self-schemas result in the production of
      depressive cognition. METHOD: Individuals with major depressive disorder (MDD,
      n=43) versus healthy (n=36) and non-depressed anxious (n=32) controls were
      assessed on the Prose Distraction Task (PDT), a measure of cognitive inhibition,
      and the Stop-Signal Task (SST), a measure of motor response inhibition. These two
      tasks were modified in order to present emotionally valenced semantic stimuli
      (i.e. negative, neutral, positive). RESULTS: Participants with MDD demonstrated
      performance impairments on the PDT, which were most pronounced for negatively
      valenced adjectives, relative to both control groups. Moreover, these impairments
      correlated with self-report measures of negative thinking and rumination.
      Conversely, the performance of the MDD participants did not differ from either
      control group on the SST. CONCLUSIONS: Implications of these findings for
      understanding the mechanisms underlying the development and maintenance of
      depressive cognition are discussed.

PMID- 17451631
TI  - Label-free detection of Babesia bovis infected red blood cells using impedance
      spectroscopy on a microfabricated flow cytometer.
AB  - Impedance spectroscopy is a powerful tool for label-free analysis and
      characterisation of living cells. In this work, we achieved the detection of
      Babesia bovis infected red blood cells using impedance spectroscopy on a
      microfabricated flow cytometer. The cellular modifications caused by the
      intracellular parasite result in a shift in impedance which can be measured
      dielectrically. Thus, a rapid cell-by-cell detection with microliter amounts of
      reagents is possible. Unlike other diagnostic tests, this method does not depend
      on extensive sample pre-treatment or expensive chemicals and equipment.

PMID- 17451632
TI  - Intraspecific variation within Phlebotomus sergenti Parrot (1917) (Diptera:
      Psychodidae) based on mtDNA sequences in Islamic Republic of Iran.
AB  - An intraspecific study on the morphological and molecular characteristics of
      Phlebotomus sergenti s.l., the main vector of Leishmania tropica, was performed
      on 28 Iranian populations from 11 provinces and a few samples from Greece,
      Morocco, Lebanon, Turkey, Pakistan, and Syria. Three morphotypes were identified
      as A, B and C, with some intermediate forms in the samples under investigation.
      Based on the number of setae and the width of basal lobe of coxite, differences
      between A and B morphotypes were highly significant. Excluding one unusual
      haplotype, sequence analysis of approximately 439 bp of mtDNA (a fragment of
      cytochrome B gene, tRNA for serine gene, and a fragment of NADH1 gene) revealed a
      6-7% genetic distance within the Iranian populations and among the specimens of
      other countries. Neighbor-Joining (NJ) analysis confirmed the existence of three
      main groups within our samples. Although there was no consistency between
      morphotypes and genotypes, but an interrelationship was found between morphometry
      and morphotypes. Morphotype A, which was considered as P. sergenti sergenti, was
      the most prevalent in collection sites. Morphotype B, which was identified as
      Phlebotomus sergenti similis, is the first record of this subspecies in Iran, and
      was found to be sympatric with other morphotypes. Morphotype C had an elongated
      style in comparison with P. sergenti sergenti. Molecular database showed three
      main genetic structures. This is the first combined morphological and molecular
      studies on P. sergenti s.l. in Iran.

PMID- 17451633
TI  - Variables that modulate the spatial distribution of Trypanosoma cruzi and
      Trypanosoma evansi in the Brazilian Pantanal.
AB  - An evaluation was made on how the landscape and cattle ranching affect the
      transmission cycles and the patterns of tripanosomatid infection (Trypanosoma
      cruzi and Trypanosoma evansi) of small wild mammals in the Pantanal. This region
      comprises a large natural environment with a multiplicity of habitats, wide
      variety of biodiversity besides the presence of livestock. T. cruzi and T. evansi
      infections were evaluated by parasitological and serological methods in one
      preserved and one cattle ranching area. The diversity of the small mammal fauna
      showed to be the same in the two studied areas, however, their relative abundance
      was different. Distinct enzootiological scenarios of both trypanosomatids could
      be observed. Transmission of T. cruzi occurred mainly in forested areas, in the
      two study areas, while T. evansi occurred dispersed among all habitats studied in
      the unpreserved area. The arboreal rodent Oecomys mamorae, the most abundant
      species in both areas, displayed high T. cruzi and T. evansi serum prevalence and
      parasitemias. Also, the caviomorph rodent Thrichomys pachyurus was shown to be an
      important host due to its expressive relative abundance, prevalence of infection
      by both trypanosomatid species and a broad range use of habitats. The role of the
      small mammal fauna in the transmission cycle of both trypanosomes species seems
      to be distinct according to land use since we found a broad range of T. evansi
      infected hosts in the preserved area in contrast to cattle ranching area and a
      half number of the rodents species infected with T. cruzi in unpreserved in
      comparison to protect area. The present study showed that cattle ranching in this
      study area did not enhance overall prevalence of T. cruzi infection among small
      wild mammals. Together with the observation that small mammals diversity in FA is
      similar to RN area suggest that ranching activity may also not necessarily
      conduct to biodiversity loss or risk of Chagas disease.

PMID- 17451634
TI  - Energy management displays: a new concept for the civil flight deck.
AB  - There exists a strong rationale for an energy management system onboard civil
      aircraft; this is based on a global move towards greater energy consciousness and
      more specific reasons relating to safety and efficiency in the airline industry.
      This paper considers the design of an interface for an energy management system.
      It reports the development of a number of display designs within the requirements
      and constraints of the flight deck context. Three designs are evaluated both with
      student participants and senior airline pilots. It was found that those displays
      with predictive information elements produced the most accurate decisions
      concerning aircraft energy states. Further investigation into the function of
      these predictive elements (within real-time flight scenarios) is required in
      order to evaluate their efficacy with the end-user group of airline pilots.

PMID- 17451635
TI  - Changing the role of the air traffic controller: how will free flight affect
      memory for spatial events?
AB  - At present, air traffic controllers (ATCOs) exercise strict control over routing
      authority for aircraft movement in airspace. The onset of a free flight
      environment, however, may well result in a dramatic change to airspace
      jurisdictions, with aircraft movements for the large part being governed by
      aircrew, not ATCOs. The present study examined the impact of such changes on
      spatial memory for recent and non-recent locations of aircraft represented on a
      visual display. The experiment contrasted present conditions, in which permission
      for manoeuvres is granted by ATCOs, with potential free flight conditions, in
      which aircrew undertake deviations without explicit approval from ATCOs. Results
      indicated that the ATCO role adopted by participants impacted differently on
      short-term and long-term spatial representations of aircraft manoeuvres. Although
      informing participants of impending deviations has beneficial effects on spatial
      representations in the short term, long-term representations of spatial events
      are affected deleteriously by the presentation of subsequent information
      pertaining to other aircraft. This study suggests strongly that recognition of
      the perceptual and cognitive consequences of changing to a free flight
      environment is crucial if air safety is not to be jeopardized.

PMID- 17451636
TI  - Multiple domains of endopin 2A for serpin cross-class inhibition of papain.
AB  - The serpin endopin 2A inhibits the cysteine protease papain in cross-class
      inhibition. This study demonstrates the novel finding that both the non-RSL NH(2)
      domain and the RSL domain with P1-P1' residues participate in endopin 2A
      inhibition. Production of a chimeric mutant of endopin 2A with replacement of its
      NH(2)-domain with that of endopin 1 resulted in less effective inhibition of
      papain, indicated by its lower k(ass) association rate constant compared to wild
      type endopin 2A. This chimeric mutant formed complexes with papain, but at lower
      levels compared to that with wild-type endopin 2A. Papain degradation of a
      portion of the chimeric mutant suggested a role for the NH(2)-domain in
      regulating relative amounts of endopin 2A that enter the substrate pathway
      compared to the serpin inhibitory pathway. Furthermore, site-directed mutagenesis
      demonstrated that the RSL domain with intact P1-P1' residues was necessary for
      inhibition. These findings indicate that the NH(2)-domain and the RSL region both
      participate in endopin 2A inhibition of papain.

PMID- 17451637
TI  - Down-regulation of N-acetylglucosaminyltransferase-V induces ER stress by
      changing glycosylation and function of GLUT1.
AB  - N-Acetylglucosaminyltransferase-V (GnT-V) is a key enzyme in the processing of N
      glycans during synthesis of glycoproteins. We have reported that down-regulating
      GnT-V could induce endoplasmic reticulum stress (ER stress) in 7721 cells, a
      human hepatocarcinoma cell line. In a search for mechanisms of ER stress, we
      found that there was a prominent decline of glucose uptake in antisense GnT-V
      transfectant, furthermore, a decrease of tri- or tetra-antannary sugar chain of
      glucose transporter 1 (GLUT1). However, distribution of GLUT1 in antisense GnT-V
      transfectant was not affected. Glucose deprivation has been known to activate ER
      stress in tumor cells. Therefore, the data presented in this study indicate that
      the glycosylation change and decrease of transport activity of GLUT1 may be one
      possible mechanism of ER stress induced by down-regulating GnT-V, and GnT-V may
      contribute to the regulation of glucose uptake by modifying glycosylation of
      GLUT1 in some tumor cells.

PMID- 17451638
TI  - Solubility of calcium fluoride and fluorapatite by solid titration.
AB  - OBJECTIVES: The solubility isotherms, S, of two compounds detected after topical
      fluoride treatment - calcium fluoride (CaF(2)) and fluorapatite (FAp) - are of
      fundamental interest in saliva chemistry and in the context of reduction of acid
      dissolution of teeth, whether through the process of caries or from exogenously
      ingested acids. Solid titration has shown its reliability and reproducibility for
      complicated systems that are not suitable for study by the traditional excess
      solid method. The primary aim of this work was to ascertain S[CaF(2)] and S[FAp].
      METHODS: Solid titration was used for CaF(2) (pH 2.3-9.5) and FAp (pH 2.8-5.1) in
      100mM KCl solution at 37.0+/-0.1 degrees C, and further to determine the apparent
      solubility of hydroxyapatite (HAp) in the presence of 1mM fluoride (pH 3.2-4.8).
      RESULTS: Peculiar results were obtained at first which were attributed to the
      adsorption or reaction of fluoride with the reaction vessel glass surface
      interfering with the intended solution equilibria. Wax-lined glass apparatus
      resolved this problem. The solubility isotherm of CaF(2) was then as
      theoretically expected at pH<8, but above this point a new solid species (CaFOH)
      was postulated to account for the data. The position of FAp was as expected
      relative to HAp, being about 0.63x less soluble. FAp was the only detectable
      equilibrium solid at pH 3.2, 3.6 and 4.1. The apparent solubility of HAp was
      depressed somewhat by the presence of 1mM fluoride. CONCLUSION: The solid
      titration method was again found to be reliable once glass interferences were
      eliminated. The interaction of fluoride with borosilicate glass may have affected
      other work in the field; such work may therefore require re-evaluation. The
      S[FAp] is very similar to that of HAp determined by solid titration. Excess-solid
      method results are strongly discrepant from the present determination and may not
      be reliable, primarily due to lack of solution speciation data for that
      calculation.

PMID- 17451640
TI  - Nanosized bilayer disks: attractive model membranes for drug partition studies.
AB  - Stable nanosized bilayer disks were prepared from either 1,2-distearoyl-sn
      glycero-3-phosphocholine (DSPC) and cholesterol, or lipid mixtures with a
      composition reflecting that of the porcine brush border membrane. Two different
      polyethylene glycol (PEG)-grafted lipids, the negatively charged 1,2-distearoyl
      sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-5000] (DSPE
      PEG(5000)) and the neutral N-palmitoyl-sphingosine-1-[succinyl (methoxy
      (polyethylene glycol) 5000] (Ceramide-PEG(5000)), were used to stabilize the
      disks. The disks were employed as model membranes in drug partition studies based
      on a fast chromatography method. Results show that the lipid composition, as well
      as the choice of PEG-lipid, have an important influence on the partition behavior
      of charged drugs. Comparative studies using multilamellar liposomes indicate that
      bilayer disks have the potential to generate more accurate partition data than do
      liposomes. Further, initial investigations using bacteriorhodopsin suggest that
      membrane proteins can be reconstituted into the bilayer disks. This fact further
      strengthens the potential of the bilayer disk as an attractive model membrane.

PMID- 17451639
TI  - Physical properties of the lipid bilayer membrane made of calf lens lipids: EPR
      spin labeling studies.
AB  - The physical properties of a membrane derived from the total lipids of a calf
      lens were investigated using EPR spin labeling and were compared with the
      properties of membranes made of an equimolar 1-palmitoyl-2
      oleoylphosphatidylcholine/cholesterol (POPC/Chol) mixture and of pure POPC.
      Conventional EPR spectra and saturation-recovery curves show that spin labels
      detect a single homogenous environment in all three membranes. Profiles of the
      order parameter, hydrophobicity, and oxygen transport parameter are practically
      identical in lens lipid and POPC/Chol membranes, but differ drastically from
      profiles in pure POPC membranes. In both lens lipid and POPC/Chol membranes, the
      lipids are strongly immobilized at all depths, which is in contrast to the high
      fluidity of the POPC membrane. Hydrophobicity and oxygen transport parameter
      profiles in lens lipid and POPC/Chol membranes have a rectangular shape with an
      abrupt change between the C9 and C10 positions, which is approximately where the
      steroid ring structure of cholesterol reaches into the membrane. At this
      position, hydrophobicity increases from the level of methanol to the level of
      hexane, and the oxygen transport parameter increases by a factor of 2-3. These
      profiles in POPC membranes are bell-shaped. It is concluded that the high level
      of cholesterol in lens lipids makes the membrane stable, immobile, and
      impermeable to both polar and nonpolar molecules.

PMID- 17451641
TI  - PrP106-126 amide causes the semi-penetrated poration in the supported lipid
      bilayers.
AB  - A major hallmark of prion diseases is the cerebral amyloid accumulation of the
      pathogenic PrP(Sc), an abnormally misfolded, protease-resistant, and beta-sheet
      rich protein. PrP106-126 is the key domain responsible for the conformational
      conversion and aggregation of PrP. It shares important physicochemical
      characteristics with PrP(Sc) and presents similar neurotoxicity as PrP(Sc). By
      combination of fluorescence polarization, dye release assay and in situ time
      lapse atomic force microscopy (AFM), we investigated the PrP106-126 amide
      interacting with the large unilamellar vesicles (LUVs) and the supported lipid
      bilayers (SLBs). The results suggest that the interactions involve a poration
      mediated process: firstly, the peptide binding results in the formation of pores
      in the membranes, which penetrate only half of the membranes; subsequently,
      PrP106-126 amide undergoes the poration-mediated diffusion in the SLBs,
      represented by the formation and expansion of the flat high-rise domains (FHDs).
      The possible mechanisms of the interactions between PrP106-126 amide and lipid
      membranes are proposed based on our observations.

PMID- 17451642
TI  - Is cognitive behaviour therapy for chronic fatigue syndrome also effective for
      pain symptoms?
AB  - Patients with chronic fatigue syndrome (CFS) frequently report chronic pain
      symptoms. Cognitive behavioural therapy (CBT) for CFS results in a reduction of
      fatigue, but is not aimed at pain symptoms. In this study, we tested the
      hypothesis that a successful treatment of CFS can also lead to a reduction of
      pain. The second objective was to explore possible mechanisms of changes in pain.
      The third objective was to assess the predictive value of pain for treatment
      outcome. Data from two previous CBT studies were used, one of adult CFS patients
      (n=96) and one of adolescent CFS patients (n=32). Pain severity was assessed with
      a daily self-observation list at baseline and post-treatment. The location of
      pain in adults was assessed with the McGill Pain Questionnaire (MPQ). Patients
      were divided into recovered and non-recovered groups. Recovery was defined as
      reaching a post-treatment level of fatigue within normal range. Recovered adult
      and adolescent CFS patients reported a significant reduction of pain severity
      compared to non-recovered patients. Recovered adult patients also had fewer pain
      locations following treatment. The decrease in fatigue predicted the change in
      pain severity. In adult patients, a higher pain severity at baseline was
      associated with a negative treatment outcome.

PMID- 17451643
TI  - Contextual control of human fear associations in a renewal paradigm.
AB  - The original model of behavior change suggests that extinction is context
      dependent whereas fear acquisition is context independent [Bouton, M. E. &
      Ricker, S. T. (1994). Renewal of extinguished responding in a second context.
      Animal Learning and Behavior, 22, 317-324]. Supportive evidence stems mainly from
      animal studies, showing that after acquisition (conditioned stimulus
      unconditioned stimulus (CS-US)) in Context A and extinction in Context B, fear is
      renewed by presenting the CS in acquisition Context A (ABA renewal) or in a novel
      Context C (ABC renewal). By implication, the model predicts equal ABA and ABC
      renewal. However, there is also evidence to suggest that the context dependency
      of extinction and the context independency of acquisition may be less stringent
      than originally proposed. The present study investigated renewal in humans using
      a differential fear conditioning paradigm with a shock US and online shock
      expectancy ratings and electrodermal responses as dependent variables. Experiment
      1 compared an ABA condition with an AAA condition. Experiment 2 compared three
      conditions: ABA, ABC, and AAA. Both experiments demonstrated ABA renewal. Most
      importantly, Experiment 2 showed larger ABA than ABC renewal. Overall, results
      for expectancy ratings were more convincing than for electrodermal responses. In
      line with the extinction model, the present findings support the context
      dependency of extinction in humans. In contrast to the model, the findings
      suggest that in humans not only extinction learning, but also fear acquisition is
      controlled by its current context.

PMID- 17451644
TI  - L-type calcium channels are preferentially coupled to endocytosis in bovine
      chromaffin cells.
AB  - Exocytosis and endocytosis are Ca(2+)-dependent processes. The contribution of
      high-voltage activated Ca(2+) channels subtypes to exocytosis has been thoroughly
      studied in chromaffin cells. However, similar reports concerning endocytosis are
      unavailable. Thus, we studied here the effects of blockers of L (nifedipine), N
      (omega-conotoxin GVIA) and P/Q (omega-agatoxin IVA) Ca(2+) channel on Ca(2+)
      currents (I(Ca)), Ca(2+) entry (Q(Ca)), as well as on the changes in membrane
      capacitance (C(m)) in perforated-patch voltage-clamped bovine adrenal chromaffin
      cells. Using 500-ms pulses to 0 or +10 mV, given from a holding potential of -80
      mV and 2 mM Ca(2+) we found that omega-conotoxin GVIA affected little the exo
      endocytotic responses while omega-agatoxin IVA markedly blocked those responses.
      However, nifedipine blocked little exocytosis but almost completely inhibited
      endocytosis. We conclude that L-type Ca(2+) channels seem to be selectively
      coupled to endocytosis.

PMID- 17451645
TI  - Identification and characterization of human non-coding RNAs with tissue-specific
      expression.
AB  - We have examined the expression profile of selected non-coding RNAs (ncRNAs) in
      11 human tissues. Among 5489 full-length cDNA clones annotated as non-protein
      coding transcripts in the H-Invitational database, we chose 150 clones for
      further analysis based on their gene structure and EST information. Expression
      profiling using quantitative RT-PCR and Northern blot hybridization revealed that
      the majority of the selected ncRNAs exhibited tissue specificity: 67% are
      predominantly expressed in a restricted subset of tissues. The absolute
      quantification of representative ncRNAs revealed that the majority of ncRNAs are
      expressed as low abundance transcripts. A comparative genomic analysis revealed
      that only 27% of the selected ncRNAs have mouse counterparts. Since the
      expression patterns of the human ncRNAs having no mouse counterparts remain to be
      similar to those of the mouse ncRNAs, the expression patterns of the selected
      ncRNAs may be conserved between human and mouse.

PMID- 17451646
TI  - Nandrolone-induced hippocampal phosphorylation of NMDA receptor subunits and
      ERKs.
AB  - The age-related decline in gonadal steroids is associated with changes in mood
      and memory function. It appears that normal physiological concentrations of the
      steroids are required for adequate synaptic plasticity. However, the effects of
      high levels of androgens subsequent to misuse of anabolic androgenic steroids
      (AAS) are largely unknown. In this study, rats were given i.m. nandrolone as a
      single dose or daily for 14 days and the effects on synaptic components in
      hippocampal synaptoneurosomes were measured 24h after the last injection. Western
      blot analysis revealed that a single injection of AAS increased phosphorylation
      of the NMDA receptor subunits NR2A and NR2B and ERK1/2, while the levels of
      phosphorylated CaMKIIalpha were unaltered. No changes were seen in other synaptic
      proteins tested, i.e., BDNF, Arc, TUC-4, and beta-tubulin III. Daily
      administration of nandrolone for 2 weeks did not affect the content of any of the
      proteins tested. From this in vivo study, it is concluded that important synaptic
      components respond to a single high dose of nandrolone, an effect that may
      influence synapse function.

PMID- 17451647
TI  - Construction and characterization of a high-affinity humanized SM5-1 monoclonal
      antibody.
AB  - SM5-1 is a mouse monoclonal antibody which has a high specificity for melanoma,
      hepatocellular carcinoma, and breast cancer, making it a promising candidate for
      cancer targeting therapy. We have therefore attempted to construct a humanized
      antibody of SM5-1 to minimize its immunogenicity for potential clinical use.
      Using a molecular model of SM5-1 built by computer-assisted homology modeling,
      framework region (FR) residues of potential importance to the antigen binding
      were identified. Then, a humanized version of SM5-1 was generated by transferring
      these mouse key FR residues onto a human framework that was selected based on
      homology to the mouse framework, together with the mouse complementarity
      determining region (CDR) residues. This humanized antibody retained only six
      murine residues outside of the CDRs but was shown to possess affinity and
      specificity comparable to that of the parental antibody, suggesting that it might
      have the potential to be developed for future clinical use.

PMID- 17451648
TI  - PREDetector: a new tool to identify regulatory elements in bacterial genomes.
AB  - In the post-genomic area, the prediction of transcription factor regulons by
      position weight matrix-based programmes is a powerful approach to decipher
      biological pathways and to modelize regulatory networks in bacteria. The main
      difficulty once a regulon prediction is available is to estimate its reliability
      prior to start expensive experimental validations and therefore trying to find a
      way how to identify true positive hits from an endless list of potential target
      genes of a regulatory protein. Here we introduce PREDetector (Prokaryotic
      Regulatory Elements Detector), a tool developed for predicting regulons of DNA
      binding proteins in bacterial genomes that, beside the automatic prediction,
      scoring and positioning of potential binding sites and their respective target
      genes in annotated bacterial genomes, it also provides an easy way to estimate
      the thresholds where to find reliable possible new target genes. PREDetector can
      be downloaded freely at
      http://www.montefiore.ulg.ac.be/~hiard/PreDetector/PreDetector.php.

PMID- 17451649
TI  - A novel osteogenic helioxanthin-derivative acts in a BMP-dependent manner.
AB  - To effectively treat serious bone defects using bone regenerative medicine, there
      is a need for the development of a small chemical compound that potently induces
      bone formation. We now report a novel osteogenic helioxanthin-derivative, TH. TH
      induced osteogenic differentiation in MC3T3-E1 cells, mouse primary osteoblasts,
      and mouse embryonic stem cells. The combination of TH and bone morphogenetic
      protein (BMP) 2 induced the mRNA expression of osteoblast marker genes and
      calcification in primary fibroblasts. The TH induced the mRNA of the inhibitor of
      DNA-binding 1 (Id-1), and its osteogenic effect was inhibited by Smad6 or Noggin.
      Furthermore, TH induced the mRNA expression of Bmp4 and Bmp6. These data suggest
      that TH exerts its potent osteogenic effect in a BMP-dependent manner by
      enhancing the effects of the existing BMPs and/or increasing the expression of
      Bmp4 and Bmp6. TH may help establish a more efficient bone regeneration system.

PMID- 17451650
TI  - Comparative analysis of the catechol 2,3-dioxygenase gene locus in
      thermoacidophilic archaeon Sulfolobus solfataricus strain 98/2.
AB  - A catechol 2,3-dioxygenase (C23O) gene was found from Sulfolobus solfataricus
      strain 98/2. Heterologous thermophilic C23O expressed in Escherichia coli showed
      the highest activity against catechol and 4-chlorocatechol, and at neutral pH.
      The C23O gene located with a putative multicomponent monooxygenase (MM) gene
      cluster that exactly matched with the homologous region of S. solfataricus strain
      P2. Primary sequence comparison identified an insertion sequence (IS) element
      inserted into a putative MM protein A N-terminal fragment gene in strain 98/2.
      Both ends of the transposase gene in the IS element, ISC1234, were flanked by 19
      bp inverted repeat and 4 bp direct repeat sequences which are typical features of
      mobile elements. Our analysis and the two geographically distant origins of
      strains 98/2 and P2 (USA and Italy, respectively) suggest that the two strains
      have evolved from a common ancestor.

PMID- 17451651
TI  - *NO dissociation represents the rate limiting step for O2-mediated oxidation of
      ferrous nitrosylated Mycobacterium leprae truncated hemoglobin O.
AB  - Mycobacterium leprae truncated hemoglobin O (trHbO) protects from nitrosative
      stress and sustains mycobacterial respiration. Here, kinetics of M. leprae
      trHbO(II)-NO denitrosylation and of O(2)-mediated oxidation of M. leprae
      trHbO(II)-NO are reported. Values of the first-order rate constant for *NO
      dissociation from M. leprae trHbO(II)-NO (k(off)) and of the first-order rate
      constant for O(2)-mediated oxidation of M. leprae trHbO(II)-NO (h) are 1.3 x 10(
      4) s(-1) and 1.2 x 10(-4) s(-1), respectively. The coincidence of values of
      k(off) and h suggests that O(2)-mediated oxidation of M. leprae trHbO(II)-NO
      occurs with a reaction mechanism in which *NO, that is initially bound to
      heme(II), is displaced by O(2) but may stay trapped in a protein cavity(ies)
      close to heme(II). Next, M. leprae trHbO(II)-O(2) reacts with *NO giving the
      transient Fe(III)-OONO species preceding the formation of the final product M.
      leprae trHbO(III). *NO dissociation from heme(II)-NO represents the rate limiting
      step for O(2)-mediated oxidation of M. leprae trHbO(II)-NO.

PMID- 17451652
TI  - EHD1 regulates cholesterol homeostasis and lipid droplet storage.
AB  - Endocytic transport is critical for the subcellular distribution of free
      cholesterol and the endocytic recycling compartment (ERC) is an important
      organelle that stores cholesterol and regulates its trafficking. The C-terminal
      EHD protein, EHD1, controls receptor recycling through the ERC and affects free
      cholesterol distribution in the cell. We utilized embryonic fibroblasts from EHD1
      knockout mice (Ehd1(-/-)MEF) and SiRNA in normal MEF cells to assess the role of
      EHD1 in intracellular transport of cholesterol. Surprisingly, Ehd1(-/-)MEFs
      displayed reduced levels of esterified and free cholesterol, which returned to
      normal level upon re-introduction of wild-type, but not dysfunctional EHD1.
      Moreover, triglyceride and cholesterol storage organelles known as 'lipid
      droplets' were smaller in size in cells lacking EHD1, indicating that less
      esterified cholesterol and triglycerides were being stored. Decreased cellular
      cholesterol and reduced lipid droplet size in Ehd1(-/-)MEFs correlated with
      ineffectual cholesterol uptake via LDL receptor, suggesting involvement of EHD1
      in LDL receptor internalization.

PMID- 17451653
TI  - Epigenetic and functional analysis of IGFBP3 and IGFBPrP1 in cellular
      immortalization.
AB  - Carcinogenic transformation of a cell requires bypassing senescence and becoming
      immortalized. A cellular senescence-like phenotype can be induced in immortal Li
      Fraumeni syndrome (LFS) cells by treating them with the DNA methyltransferase
      inhibitor 5-aza-deoxycytidine. Our microarray-based expression profiling studies
      of spontaneously immortalized LFS cell lines identified genes that may provide
      the growth advantage required for the cells to become immortal. Several members
      of the IGFBP superfamily of genes fit the profile of genes involved in
      immortalization: silenced during immortalization and reactivated by 5-aza
      deoxycytidine. Overexpression of IGFBP3 or IGFBPrP1 in the immortal LFS cell
      lines suppressed cell growth and inhibited colony formation. Both genes have the
      expression pattern of an epigenetically regulated gene and contain CpG islands
      suitable for methylation-dependent silencing. Analysis of how IGFBPs regulate
      immortalization will lead to a better understanding of this process and may lead
      to novel methods for the prevention and treatment of cancer.

PMID- 17451654
TI  - A proteomics approach to identify the ubiquitinated proteins in mouse heart.
AB  - There is a growing need for the large-scale identification of the ubiquitinated
      proteins and ubiquitin attachment sites. As part of this effort, we generated a
      transgenic mouse expressing a tagged ubiquitin in the heart. We found that the
      majority of ubiquitinated proteins in mouse heart are insoluble in detergent-free
      buffer and were chemically cleaved after methionine with CNBr. CNBr cleaved the
      proteins into smaller polypeptides while preserving the ubiquitin chains.
      Ubiquitin-conjugated polypeptides were then purified under denaturing conditions,
      digested with Lys-C and trypsin, and analyzed by liquid chromatography-tandem
      mass spectrometry. We identified 121 proteins that were ubiquitinated in mouse
      heart, and we detected 33 ubiquitination sites in 21 of the proteins. Components
      of cardiac muscle and many mitochondrial proteins were identified as substrates
      for ubiquitination, strongly suggesting that proteins related to major heart
      functions such as contraction and energy production are under continuous quality
      control by the ubiquitin system.

PMID- 17451655
TI  - The cross channel activities of spider neurotoxin huwentoxin-I on rat dorsal root
      ganglion neurons.
AB  - In this paper, we investigated the action of huwentoxin-I (HWTX-I) purified from
      the venom of the Chinese bird spider Ornithoctonus huwena on Ca(2+), Na(+)
      channels of adult rat dorsal root ganglion (DRG) neurons. The results showed that
      huwentoxin-I could reduce the peak currents of N-type Ca(2+) channels (IC(50)
      approximately 100 nM) and TTX-S Na(+) channels (IC(50) approximately 55 nM),
      whereas no effect was detected on TTX-R Na(+) channels. The comparative studies
      indicated that the selectivity of HWTX-I on Ca(2+) channels was higher that of
      MVIIA and approximately the same as that of GVIA. HWTX-I is the first discovered
      toxin with the cross channel activities from the spider O. huwena venom similar
      to micro O-conotoxins MrVIA and MrVIB.

PMID- 17451656
TI  - Agonist-stimulated reactive oxygen species formation regulates beta2-adrenergic
      receptor signal transduction.
AB  - Generation of reactive oxygen species (ROS) can occur upon agonist stimulation of
      surface receptors to modulate downstream signaling processes. Here, we show that
      activation of the beta2 adrenergic receptor (beta2AR) by stimulation with the
      agonist isoproterenol leads to generation of ROS that is required for beta2AR
      signal transduction. Specifically, we show that inhibition of NADPH oxidase with
      diphenyliodonium chloride, inhibition of the small GTPase Rac1 with NSC23766, and
      inhibition of formed ROS with the antioxidant N-acetyl-L-cysteine decreases
      beta2AR-mediated cAMP formation, protein kinase A activation, and receptor
      phosphorylation and internalization, but does not impact ligand binding. The
      results also show that inhibition of ROS attenuates active beta2AR-mediated
      binding of GTP to alpha subunits of heterotrimeric G proteins. Based on these
      results, we propose that agonist-dependent ROS formation is needed for beta2AR
      signal transduction, perhaps through stabilization of active receptor conformers
      by redox-mediated modification of receptor and/or Galpha proteins cysteine
      residues.

PMID- 17451657
TI  - Top-down knowledge supports the retrieval of lexical information from degraded
      speech.
AB  - How is it that the human brain is capable of making sense from speech under many
      acoustically compromised conditions? The support through top-down knowledge is
      inevitable but can we identify brain measures of this matching process between
      degraded auditory input and possible meaning? To answer these questions, the
      present study investigated the modulation of the induced gamma-band activity
      (GBA) in the auditory domain in response to degraded speech. During an EEG
      experiment subjects first listened to digitally degraded unintelligible speech
      signals (derived from German nouns). In an exposure sequence, half of the nouns
      were presented in a non-degraded intelligible format and memorized, while in the
      crucial test sequence subjects listened to all degraded speech signals again and
      were asked to identify the words. The induced GBA (40-Hz range) showed an
      increase at left temporal electrode sites around 350 ms only for words correctly
      identified in the test sequence. No differences in induced GBA were evident in
      the baseline sequence; neither did the evoked brain potentials yield any
      comparable effect. We conclude that the observed enhancement in induced gamma
      band activity reflects a matching process of top-down lexical memory traces with
      degraded sensory input to form a comprehendible speech percept. The findings are
      highly corroborant to analogous studies in the visual system. They lend further
      plausibility to a left-lateralized fronto-temporal network enabling lexically
      guided speech perception, and they demonstrate the complementary role of time
      sensitive brain analyses in discerning the functional neuroanatomy of speech.

PMID- 17451658
TI  - Changes in serotoninergic receptors 1A and 2A in the piglet brainstem after
      intermittent hypercapnic hypoxia (IHH) and nicotine.
AB  - We studied the effects of intermittent hypercapnic hypoxia (IHH) and/or nicotine
      on the immunoreactivity of serotoninergic (5-HT) receptors 1A and 2A in the
      piglet brainstem. These exposures were developed to mimic two common risk factors
      for Sudden Infant Death Syndrome (SIDS); prone sleeping (IHH) and cigarette smoke
      exposure (nicotine). Immunoreactivity for 5-HT(1A)R and 5-HT(2A)R were studied in
      four nuclei of the caudal medulla. Three exposure groups were compared to
      controls (n=14): IHH (n=10), nicotine (n=14), and nicotine+IHH (n=14). In control
      piglets, the immunoreactivity of 5-HT(1A)R was highest in the hypoglossal nucleus
      (XII), followed by inferior olivary nucleus (ION), nucleus of the solitary tract
      (NTS) and dorsal motor nucleus of the vagus (DMNV), whereas for 5-HT(2A)R, the
      immunoreactivity was highest in DMNV/NTS and then ION. Compared to controls, IHH
      reduced 5-HT(1A)R immunoreactivity in all studied nuclei (p<0.05) but had no
      effect on 5-HT(2A)R immunoreactivity. Nicotine reduced 5-HT(1A)R immunoreactivity
      in the DMNV, ION and NTS (p<0.001), and reduced 5-HT(2A)R immunoreactivity in
      DMNV/NTS (p<0.05). Nicotine+IHH reduced 5-HT(1A)R in DMNV, ION and NTS (p<0.001)
      but had no effect on 5-HT(2A)R immunoreactivity. Effects of nicotine on the DMNV
      were more significant in males compared to the females. These results show for
      the first time that IHH and/or nicotine can reduce 5-HT receptor immunoreactivity
      within functionally important nuclei of the piglet medulla. The findings support
      our hypothesis that 5-HT receptor abnormalities may be caused by postnatal
      exposures to clinically-relevant stimuli such as cigarette smoke exposure and/or
      prone sleeping.

PMID- 17451659
TI  - Signalling by NO-induced protein S-nitrosylation and S-glutathionylation:
      convergences and divergences.
AB  - The role of nitric oxide in several signalling routes has been clearly
      established. In recent years increasing attention has been paid to its ability to
      produce covalent protein post-translational modifications in conjunction with
      other reactive oxygen and nitrogen species. Among these, the modification of
      cysteine residues has been shown to be of particular importance due to the
      functional relevance of many of them. In this review, we focus on the
      modification of the cysteine thiol by incorporation of a NO moiety (S
      nitrosylation) or of a glutathione moiety (S-glutathionylation). Both
      modifications are produced by different reactions induced by nitric oxide-related
      species. We discuss the differences and similarities of both modifications, and
      their relationships, in regard to the biochemical mechanisms that produce them,
      including the enzymatic activities that may catalyze some of them and their
      subcellular compartmentalization. Even when biochemical knowledge is one step
      ahead of the demonstration of their pathophysiological relevance, we also
      describe the potential role of both modifications in several processes in which
      both post-translational modifications are involved.

PMID- 17451660
TI  - The priority dispute over the function of the lymphatic system and Glisson's
      ghost (the 18th-century Hunter-Monro Feud).
AB  - Basic Immunology has had only two significant public priority disputes. The first
      began in the late 1650s and concerned the recognition of the peripheral network
      of vessels which collects lymph throughout the body. The publication of this
      major anatomical discovery prompted a priority feud discussed in a previous
      paper. The subject of this essay is the second dispute which occurred a century
      later in the late 1750s. It focused on the function of the lymphatic system and
      precipitated a heated war of words between a young Scotch medical graduate
      (Alexander Monro) and a noted London anatomist (William Hunter). Their published
      charges and responses ranged from feigned respect to ad hominen invectives. But
      in retrospect, the priority claims of both were precluded by the observations and
      speculations of an Englishman (Francis Glisson) a full century before. The
      several editions of his work were unknown to Hunter and Monro at the inception of
      their feud.

PMID- 17451661
TI  - High resolution NMR for studying lipid hydrolysis and esterification in cod
      (Gadus morhua) gonads.
AB  - High resolution NMR was applied to study biochemical changes of lipids in cod
      (Gadus morhua) gonads during 7 days storage at 4 degrees C. Changes were observed
      in the (13)C and (1)H resonances of cholesterol which were due to esterification
      of fatty acids at the hydroxyl position in roe and milt. Furthermore, the (13)C
      NMR spectra showed that the lipolytic changes in milt and roe where different.
      New resonances appeared during storage, due to formation of specific free fatty
      acids, with the corresponding changes in resonances of the esterified carbonyls
      and glycerols. The highly unsaturated n-3 fatty acids were hydrolysed from the sn
      1 and sn-2 position of both phosphatidylcholine and phosphatidylethanolamine in
      milt. The lipolytical changes in roe were less prominent compared to the changes
      in milt, however significant levels of sn-1-lysophospholipids was detected both
      in roe and milt. The current data demonstrate that high resolution NMR may be a
      suitable method to non-destructively study hydrolysis and esterification
      reactions occurring in heterogeneous marine lipids in a one step procedure.

PMID- 17451662
TI  - A comparative study of the effects of dimethylsulfoxide and glycerol on the
      bicontinuous cubic structure of hydrated monoolein and its phase behavior.
AB  - Both dimethylsulfoxide (DMSO) and glycerol act cryoprotectants for biological
      systems and materials. Knowledge of molecular interactions of DMSO and glycerol
      with biological lipids is important for understanding of their cryoprotecitive
      mechanisms. In this study, the phase behavior and structures of hydrated
      monoolein were investigated in the presence of DMSO or glycerol, using
      differential scanning calorimetry (DSC) and simultaneous X-ray diffraction/DSC
      measurements. Based on the results obtained by this study, partial phase diagrams
      were constructed as a function of DMSO or glycerol concentrations and
      temperature. DMSO and glycerol hardly affect the enthalpy value for melting
      temperature of lamellar crystal phase of monoolein and the structure. On the
      other hand, DMSO and glycerol greatly affect the phase transformations associated
      with bicontinuous cubic phases of monoolein and the cubic phase structures. DMSO
      expands Im3m/Pn3m cubic phase co-existence region in the phase diagram and
      increases the lattice constant of the Pn3m monoolein cubic phase. Glycerol shows
      opposite effects. The present study suggests that different mechanisms act in the
      cryopreservation by DMSO and glycerol.

PMID- 17451663
TI  - A personal history of markers of myocyte injury [myocardial infarction].
AB  - BACKGROUND: The measurement of proteins in blood to reflect damage to the heart
      is one of the most successful examples of easily measured biomarkers identifying
      a serious major health problem. The concept of using a blood test to reflect
      organ or cell injury requires a substance that is very abundant in the target
      cell, has a means of reaching blood, a reasonable half-life in blood, and ideally
      a specific form reflective only of the target cell in tissue. The myocyte's major
      role is contraction so proteins involved in contraction or the energy to support
      it should be good candidate markers. CONCLUSIONS: All the various biomarkers that
      have been used to detect cardiac damage are involved in contraction or energy
      metabolism, but the markers evolved empirically starting with transaminases in
      the 1950s leading to troponins in the 1990s. This history is reviewed with
      reflections on my experiences with developing assays for CK-MB and Troponin I.

PMID- 17451664
TI  - Induction of antiphospholipid antibodies and antiphospholipid syndrome-like
      autoimmunity in naive mice with antibody against human parvovirus B19 VP1 unique
      region protein.
AB  - BACKGROUND: Previous studies have postulated a connection between human
      parvovirus B19 (B19) infection and anti-phospholipid antibodies (APhL). B19
      infection and anti-phospholipid syndrome (APS) exhibit congruent symptoms.
      Recently, phospholipase A2 (PLA2)-like activity has been linked to the VP1 unique
      region (VP1u) of B19. However, the precise role of B19-VP1u in pathogenesis of
      autoimmunity is still obscure. METHODS: To elucidate the roles of VP1u in B19
      infection and autoimmunity, the reactivity of B19-VP1u proteins with various
      autoantibodies were evaluated by ELISA and immunoblotting. Rabbits were immunized
      with purified recombinant B19-VP1u protein to generate anti-sera. Absorption
      experiments were conducted to determine the binding specificity of rabbit anti
      sera against B19-VP1u, cardiolipin (CL) and beta-2-glycoprotein I (beta2GPI).
      Moreover, the effects of passive transfer of polyclonal rabbit anti-B19-VP1u IgG
      antibodies on platelets, activated partial thromboplastin time (aPTT), and
      autoantibodies were assessed. RESULTS: Autoantibodies against CL, beta2GPI, and
      phospholipid (PhL) in sera from patients with B19 infection, were cross-reactive
      with B19-VP1u. Consistently, sera from rabbits immunized with recombinant B19
      VP1u protein displayed raised detectable immunoglobulins against B19-VP1u, CL,
      beta2GPI and PhL. Additionally, the mice immunized with anti-B19-VP1u IgG
      developed thrombocytopenia, prolongation of aPTT, and autoantibody against
      beta2GPI and PhL. CONCLUSIONS: These experimental results suggested the
      association between B19-VP1u and production of anti-beta2GPI antibodies, APhL,
      and APS-like autoimmunity. Altogether, it may provide a clue in understanding the
      role of B19-VP1u in inducing autoantibodies and B19-associated APS
      manifestations.

PMID- 17451665
TI  - Oxidative stress varies with the mode of delivery in intrauterine growth
      retardation: association with Apgar score.
AB  - OBJECTIVE: To assess if oxidative injury in intrauterine growth retarded and
      healthy newborns is affected by the mode of delivery and whether Apgar score as a
      marker of neonatal survival is dependent on lipid and protein oxidative injury
      assessed by measuring malondialdehyde and protein carbonylation. METHODS: 30 IUGR
      newborns, 15 born by normal vaginal delivery and 15 born by elective caesarean
      section, and 40 healthy control infants, 30 born by normal vaginal delivery and
      10 born by elective caesarean section, were studied at birth. Cord blood was
      collected for determination of malondialdehyde and protein carbonylation.
      RESULTS: IUGR newborns had significantly elevated MDA and protein carbonylation
      than the control group. Apgar scores, both at 1 and 5 min, were significantly
      lower in the IUGR group. These were assessed by independent sample t test. Using
      one-way ANOVA we found that MDA and protein carbonyls levels were not
      statistically different in healthy control group and in IUGR subgroup born by
      caesarean section however they were significantly different in other groups.
      Linear regression analysis revealed that Apgar scores both at 1 min and 5 min
      were dependent on MDA in IUGR newborns. Apgar score was however not dependent on
      protein carbonylation in the same group. CONCLUSION: Apgar score in IUGR newborns
      is dependent on the extent of oxidative injury and elective caesarean section
      minimises the same.

PMID- 17451666
TI  - Differential time-dependent effects of emotion on recollective experience and
      memory for contextual information.
AB  - Emotion has been suggested to slow forgetting via a mechanism that enhances
      memory consolidation. Here, we investigate whether this time dependent process
      influences the subjective experience of recollection as well as the ability to
      retrieve specific contextual details of the study event. To do so we examined
      recognition for emotional and neutral pictures at two retention intervals and
      collected remember/know reports and reports about the task that had been
      performed with the item during encoding. Recollective experience was enhanced for
      emotional compared to neutral photos after a 24-h delay, but not immediately
      after encoding. In contrast, memory for the task performed during encoding did
      not differ between emotional and neutral photos at either time point. The
      findings indicate that emotion slows the effects of forgetting on the
      recollective experience associated with studied events, without necessarily
      slowing the forgetting of specific contextual details of those events.

PMID- 17451667
TI  - Dynamic binding of identity and location information: a serial model of multiple
      identity tracking.
AB  - Tracking of multiple moving objects is commonly assumed to be carried out by a
      fixed-capacity parallel mechanism. The present study proposes a serial model
      (MOMIT) to explain performance accuracy in the maintenance of multiple moving
      objects with distinct identities. A serial refresh mechanism is postulated, which
      makes recourse to continuous attention switching, a capacity-limited episodic
      buffer for identity-location bindings, indexed location information stored in the
      visuospatial short-term memory, and an active role of long-term memory. As
      identity-location bindings are refreshed serially, a location error is inherent
      for all other targets except the focally attended one. The magnitude of this
      location error is a key factor in predicting tracking accuracy. MOMIT's
      predictions were supported by the data of five experiments: performance accuracy
      decreased as a function of target set-size, speed, and familiarity. A
      mathematical version of MOMIT fitted nicely to the observed data with plausible
      parameter estimates for the binding capacity and refresh time.

PMID- 17451668
TI  - Vitrification of human laser treated blastocysts within cut standard straws
      (CSS): novel aseptic packaging and reduced concentrations of cryoprotectants.
AB  - Vitrification of laser treated human blastocysts using reduced concentrations of
      permeable cryoprotectants was carried out by submerging cut standard straws (CSS)
      into liquid nitrogen. The CSS were made by cutting a standard 0.25 ml straw at an
      angle of approximately 45 degrees . After laser assisted hatching, 6 day
      blastocysts (n=250) were loaded into droplets of approximately 0.75 microl in the
      CSS and were either plunged directly into liquid nitrogen or first encased in a
      standard 0.5 ml straw (aseptic technique) before being vitrified. Permeable
      cryoprotectants (ethylene glycol+Me(2)SO) at concentrations of 15% and 20% v:v
      were tested for their effect on post warming re-expansion and post transfer
      pregnancy rates. Our results indicate that the use of reduced concentrations of
      cryoprotectants and aseptic packaging of blastocysts did not have any
      statistically significant impact on the study outcomes.

PMID- 17451669
TI  - Improvement of the quality of boar cryopreservation semen by supplementing with
      low density lipoprotein in diluents.
AB  - Low density lipoprotein was added at concentrations of 6%, 7%, 8%, 9% and 10% to
      the diluents used to freeze boar semen and its effect on the quality of
      cryopreservation was assessed The results indicated that 9% low density
      lipoprotein supplementation significantly improved the total motile sperm
      (p<0.05). The sperm straight-line velocity increased with the concentration of
      low density lipoprotein except at the concentration of 10%, at which
      concentration the sperm velocity declined (p<0.05). Supplementation at 8% and 9%
      low density lipoprotein significantly increased plasma membrane integrity
      (p<0.05). Compared with control, the low density lipoprotein supplementation
      significantly improved the percentage of acrosome integrity (p<0.05). With all
      parameters measured, the concentration of 9% low density lipoprotein showed a
      better effect on the quality of boar cryopreservation semen. The sperm DNA was
      more seriously damaged in the species of Yorkshire than in Duroc.

PMID- 17451670
TI  - The MEK inhibitor, U0126, alters fertilization-induced [Ca2+]i oscillation
      parameters and secretion: differential effects associated with in vivo and in
      vitro meiotic maturation.
AB  - Although mitogen-activated protein kinase (MAPK) is a well-known cell cycle
      regulator, emerging studies have also implicated its activity in the regulation
      of intracellular calcium concentration ([Ca2+](i)) and secretion. Those studies
      raise the hypothesis that MAPK activity during oocyte maturation and early
      fertilization is required for normal egg Ca2+ oscillations and cortical granule
      (CG) secretion. We extend the findings of [Lee, B., Vermassen, E., Yoon, S.-Y.,
      Vanderheyden, V., Ito, J., Alfandari, D., De Smedt, H., Parys, J.B., Fissore,
      R.A., 2006. Phosphorylation of IP(3)R1 and the regulation of [Ca2+](i) responses
      at fertilization: a role for the MAP kinase pathway. Development 133, 4355-4365]
      by demonstrating acute effects on Ca2+ oscillation frequency, amplitude, and
      duration in fertilized mouse eggs matured in vitro with the MAPK inhibitor,
      U0126. Frequency was increased, whereas amplitude and duration were greatly
      decreased. These effects were significantly reduced in eggs matured in vivo and
      fertilized in the presence of the inhibitor. Ionomycin studies indicated that
      intracellular Ca2+ stores were differentially affected in eggs matured in vitro
      with U0126. Consistent with these effects on [Ca2+](i) elevation, fertilization
      induced CG exocytosis and metaphase II exit were also reduced in in vitro-matured
      eggs with U0126, but not in those similarly treated after in vivo maturation.
      These results indicate that MAPK targets Ca2+ regulatory proteins during both
      maturation and fertilization, as well as provide a new hypothesis for MAPK
      function, which is to indirectly regulate events of early development by
      controlling Ca2+ oscillation parameters.

PMID- 17451671
TI  - Cis-regulatory control of the nodal gene, initiator of the sea urchin oral
      ectoderm gene network.
AB  - Expression of the nodal gene initiates the gene regulatory network which
      establishes the transcriptional specification of the oral ectoderm in the sea
      urchin embryo. This gene encodes a TGFbeta ligand, and in Strongylocentrotus
      purpuratus its transcription is activated in the presumptive oral ectoderm at
      about the 30-cell stage. Thereafter Nodal signaling occurs among all cells of the
      oral ectoderm territory, and nodal expression is required for expression of oral
      ectoderm regulatory genes. The cis-regulatory system of the nodal gene transduces
      anisotropically distributed cytoplasmic cues that distinguish the future oral and
      aboral domains of the early embryo. Here we establish the genomic basis for the
      initiation and maintenance of nodal gene expression in the oral ectoderm.
      Functional cis-regulatory control modules of the nodal gene were identified by
      interspecific sequence conservation. A 5' cis-regulatory module functions both to
      initiate expression of the nodal gene and to maintain its expression by means of
      feedback input from the Nodal signal transduction system. These functions are
      mediated respectively by target sites for bZIP transcription factors, and by SMAD
      target sites. At least one SMAD site is also needed for the initiation of
      expression. An intron module also contains SMAD sites which respond to Nodal
      feedback, and in addition acts to repress vegetal expression. These observations
      explain the main features of nodal expression in the oral ectoderm: since the
      activity of bZIP factors is redox sensitive, and the initial polarization of oral
      vs. aboral fate is manifested in a redox differential, the bZIP sites account for
      the activation of nodal on the oral side; and since the immediate early signal
      transduction response factors for Nodal are SMAD factors, the SMAD sites account
      for the feedback maintenance of nodal gene expression.

PMID- 17451672
TI  - Understanding international crime trends: the legacy of preschool lead exposure.
AB  - This study shows a very strong association between preschool blood lead and
      subsequent crime rate trends over several decades in the USA, Britain, Canada,
      France, Australia, Finland, Italy, West Germany, and New Zealand. The
      relationship is characterized by best-fit lags (highest R2 and t-value for blood
      lead) consistent with neurobehavioral damage in the first year of life and the
      peak age of offending for index crime, burglary, and violent crime. The impact of
      blood lead is also evident in age-specific arrest and incarceration trends.
      Regression analysis of average 1985-1994 murder rates across USA cities suggests
      that murder could be especially associated with more severe cases of childhood
      lead poisoning.

PMID- 17451673
TI  - Polychlorinated biphenyls (PCBs) in San Francisco Bay.
AB  - San Francisco Bay is facing a legacy of polychlorinated biphenyls (PCBs) spread
      widely across the land surface of the watershed, mixed deep into the sediment of
      the Bay, and contaminating the Bay food web to a degree that poses health risks
      to humans and wildlife. In response to this persistent problem, water quality
      managers are establishing a PCB total maximum daily load (TMDL) and
      implementation plan to accelerate the recovery of the Bay from decades of PCB
      contamination. This article provides a review of progress made over the past 15
      years in managing PCBs and understanding their sources, pathways, fate, and
      effects in the Bay, and highlights remaining information needs that should be
      addressed in the next 10 years. The phaseout of PCBs during the 1970s and the
      1979 federal ban on sale and production led to gradual declines from the 1970s to
      the present. However, 25 years after the ban, PCB concentrations in some Bay
      sport fish today are still more than ten times higher than the threshold of
      concern for human health. Without further management action it appears that the
      general recovery of the Bay from PCB contamination will take many more decades.
      PCB concentrations in sport fish were, along with mercury, a primary cause of a
      consumption advisory for the Bay and the consequent classification of the Bay as
      an impaired water body. Several sources of information indicate that PCB
      concentrations in the Bay may also be high enough to adversely affect wildlife,
      including rare and endangered species. The greater than 90% reduction in food web
      contamination needed to meet the targets for protection of human health would
      likely also generally eliminate risks to wildlife. PCB contamination in the Bay
      is primarily associated with industrial areas along the shoreline and in local
      watersheds. Strong spatial gradients in PCB concentrations persist decades after
      the release of these chemicals to Bay Area waterways. Through the TMDL process,
      attention is being more sharply focused on the PCB sources that are controllable
      and contributing most to PCB impairment in the Bay. Urban runoff from local
      watersheds is a particularly significant pathway for PCB entry into the Bay.
      Significant loads also enter the Bay through Delta outflow (riverine input).
      Recent studies have shown that erosion of buried sediment is occurring in large
      regions of the Bay, posing a significant problem with respect to recovery of the
      Bay from PCB contamination because the sediments being eroded and remobilized are
      from relatively contaminated buried sediment deposits. In-Bay contaminated sites
      are likely also a major contributor of PCBs to the Bay food web. Dredged material
      disposal, wastewater effluent, and atmospheric deposition are relatively minor
      pathways for PCB loading to the Bay. Priority information needs at present relate
      to understanding the sources, magnitude of loads, and effectiveness of management
      options for urban runoff; the regional influence of in-Bay contaminated sites;
      remobilization of PCBs from buried sediment; historic and present trends; in situ
      degradation rates of PCBs; reliable recovery forecasts under different management
      scenarios; the spatial distribution of PCBs in soils and sediments; and the
      biological effects of PCBs in interaction with other stressors. The slow release
      of pollutants from the watershed and the slow response of the Bay to changes in
      inputs combine to make this ecosystem very slow to recover from pollution of the
      watershed. The history of PCB contamination in the Bay underscores the importance
      of preventing persistent, particle-associated pollutants from entering this
      sensitive ecosystem.

PMID- 17451674
TI  - Possible involvement of spinal noradrenergic mechanisms in the antiallodynic
      effect of intrathecally administered 5-HT2C receptor agonists in the rats with
      peripheral nerve injury.
AB  - Intrathecal administration of serotonin type 2C (5-HT(2C)) receptor agonists
      produces an antiallodynic effect in a rat model of neuropathic pain. In the
      present study, we characterized this effect pharmacologically. Allodynia was
      produced by tight ligation of the fifth (L5) and sixth (L6) lumbar spinal nerves
      on the left side, and was measured by applying von Frey filaments to the left
      hindpaw. 6-chloro-2-(1-piperazinyl)-pyrazine (MK212; 100 microg) and 1-(m
      chlorophenyl)-piperazine (mCPP; 300 microg) were used as 5-HT(2C) receptor
      agonists. Intrathecal administration of these agonists resulted in an
      antiallodynic effect. Intrathecal administration of atropine (30 mug), a
      muscarinic receptor antagonist, and yohimbine (30 microg), an alpha(2)
      adrenoceptor antagonist, reversed the effects of 5-HT(2C) receptor agonists.
      Intrathecal pretreatment with 6-hydroxydopamine, an adrenergic neurotoxin,
      inhibited the antiallodynic effect of MK212. These results suggest that spinal
      noradrenergic mechanisms are involved in the antiallodynic effects of
      intrathecally administered 5-HT(2C) receptor agonists. Previously, we
      demonstrated that intrathecal administration of 5-HT(2A) receptor agonists also
      produced antiallodynic effects, and the effects were not reversed by yohimbine.
      Taken together, these findings suggest that 5-HT(2A) and 5-HT(2C) receptors in
      the dorsal horn of the spinal cord might be involved in alleviating neuropathic
      pain by different mechanisms.

PMID- 17451675
TI  - Functional properties of a novel mutant of staphylokinase with platelet-targeted
      fibrinolysis and antiplatelet aggregation activities.
AB  - The present study was performed to characterize the functional properties of RGD
      SAK, a novel mutant of staphylokinase (SAK). Biochemical analysis indicated that
      RGD-SAK maintained the similar structure and the fibrinolytic function of SAK.
      Measurement of platelet binding activity in vitro demonstrated that RGD-SAK had a
      much higher affinity with platelets than SAK. In vitro platelet-rich clot lysis
      assay demonstrated that the engineered mutant outperformed the non-manipulated
      SAK. The time required for 50% platelet-rich clot lysis was reduced significantly
      across different concentrations of RGD-SAK comparing with SAK. Meanwhile, RGD-SAK
      was found to inhibit ADP-induced platelet aggregation in a concentration
      dependent manner while SAK had negligible effect on platelet aggregation. In
      concordance, further study in a porcine coronary balloon injury model
      demonstrated the efficacy of RGD-SAK for the lysis of platelet-rich coronary
      blood clots and for the prevention of reocclusion after thrombolysis. These
      results suggested that RGD-SAK may serve as a potential thrombolytic agent with
      platelet-targeted fibrinolysis and antiplatelet aggregation activities.

PMID- 17451676
TI  - Early and sharp nitric oxide production and anoxic depolarization in the rat
      hippocampus during transient forebrain ischemia.
AB  - This study was designed to characterize nitric oxide (NO) production and anoxic
      depolarization in the rat hippocampus during transient forebrain ischemia using
      two NO synthase (NOS) inhibitors, L-N(5)-(1-iminoethyl)ornithine (L-NIO), a
      relatively selective endothelial NOS (eNOS) inhibitor, and 7-nitroindazole, a
      relatively selective neuronal NOS (nNOS) inhibitor, and an NO scavenger, [2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide] (carboxy-PTIO). We
      measured the mean arterial blood pressure, hippocampal blood flow, NO
      concentration and direct current potential before, during and after transient
      forebrain ischemia, which was induced by 4-vessel occlusion for 10 min. Saline, L
      NIO (20 mg/kg), 7-nitroindazole (25 mg/kg), L-NIO (20 mg/kg)+7-nitroindazole (25
      mg/kg) or carboxy-PTIO (1 mg/kg) was administered intraperitoneally 20 min before
      the onset of ischemia. We observed early and sharp NO production in the
      hippocampus during ischemia in the saline group. This NO increase during ischemia
      was significantly reduced by L-NIO (20 mg/kg)+7-nitroindazole (25 mg/kg) or
      carboxy-PTIO (1 mg/kg), but not L-NIO (20 mg/kg) or 7-nitroindazole (25 mg/kg).
      On the other hand, NO production after ischemia was significantly reduced by 7
      nitroindazole (25 mg/kg), L-NIO (20 mg/kg)+7-nitroindazole (25 mg/kg) or carboxy
      PTIO (1 mg/kg), but not L-NIO (20 mg/kg). The peak latency of NO production
      during ischemia always preceded the onset latency of anoxic depolarization in
      both the saline group and the carboxy-PTIO group. In the carboxy-PTIO group, the
      onset latency of anoxic depolarization was significantly longer than that in the
      saline group. Moreover, carboxy-PTIO significantly reduced the anoxic
      depolarization amplitude, compared with that of the saline group. These results
      suggest that both NOS-dependent and-independent NO formation contributes to early
      and sharp NO production during ischemia, and that this NO increase is, at least
      in part, related to the triggering of anoxic depolarization.

PMID- 17451677
TI  - Na+/K+-ATPase alpha isoforms expression in stroke-prone spontaneously
      hypertensive rat heart ventricles: effect of salt loading and lacidipine
      treatment.
AB  - Changes in myocardial expression of Na+/K+-ATPase alpha-subunit isoforms have
      been demonstrated in different models of cardiac hypertrophy and hypertension.
      Here we studied the expression of these isozymes in stroke-prone spontaneously
      hypertensive rats (SHRSP) and the influence of high salt diet and treatment with
      the dihydropyridine lacidipine. Adult SHRSP were offered either 1% NaCl or water
      as drinking solution for 6 weeks. Salt-loaded SHRSP were treated or not with 1
      mg/kg/day lacidipine. Compared to Wistar Kyoto (WKY) rats, non-salt-loaded SHRSP
      presented significant hypertension and cardiac hypertrophy. Salt intake markedly
      enhanced cardiac hypertrophy, an effect blunted by lacidipine. [3H]Ouabain
      binding assays on total particulate fractions from heart ventricles revealed the
      existence of two high-affinity sites with Kd approximately 25 and approximately
      200 nM, ascribed to the alpha3 and alpha2 isoforms, respectively. Bmax of alpha3
      was unexpectedly high (40% of total high-affinity binding) in ventricles from WKY
      rats but very low in all groups of SHRSP. On the other hand, Bmax of alpha2 was
      similar in WKY and non-salt-loaded SHRSP; however, salt loading of SHRSP resulted
      in a Bmax reduction of 20% (P<0.05), an effect blocked by lacidipine. These
      effects were largely confirmed by immunoblotting analysis, which, in addition,
      demonstrated that the density of the ubiquitous alpha1 isoform was comparable
      among the experimental groups. In conclusion, WKY rats showed a high myocardial
      expression of the Na+/K+-ATPase alpha3 subunit, which was not found in SHRSP; the
      level of the alpha2 isoform was similar in untreated SHRSP and WKY; salt-loading
      of SHRSP promoted reduction of the alpha2 isoform, and this effect was completely
      hampered by lacidipine.

PMID- 17451678
TI  - Effects of neuropeptide Y2 receptor blockade on ventricular arrhythmias in rats
      with acute myocardial infarction.
AB  - Excessive sympathetic activity is believed to be the key arrhythmogenic factor
      both in the setting of acute myocardial infarction and during chronic heart
      failure. The aim of this study was to evaluate the effect of neuropeptide Y2
      blockade on malignant ventricular arrhythmias in rats with acute myocardial
      infarction. Vagotonic dose-finding study for neuropeptide Y2 receptor antagonist,
      (S)-N2-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b,e]azepin-11-yl]-1-piperazinyl]
      2-oxoethyl] cylopentyl] acetyl]-N-[2-[1,2-dihydro-3,5 (4H)-dioxo-1,2-diphenyl-3H
      1,2,4-triazol-4-yl]ethyl]-argininamid (AR-H05359) was conducted in guinea pigs
      (n=50) and rats (n=3). Induction of postinfarction arrhythmias was conducted in
      Sprague-Dawley rats that were randomized into 3 groups. Neuropeptide Y2
      antagonist treated rats (n=7), placebo group (n=10) and amiodarone treated rats
      (n=8). Myocardial infarction was induced by ligation of the left coronary artery.
      Computerized telemetric ECG tracings were obtained continuously before induction
      of myocardial infarction and up to 120 min postinfarction. Occurrence of
      ventricular arrhythmias was analyzed according to a 10-point arrhythmia score.
      There was no difference in the arrhythmia scores between the neuropeptide Y2 and
      the saline group. The amiodarone treated animals had lower score compared to the
      neuropeptide Y2 and the placebo group (p<0.05). The blockade of receptors does
      not reduce ventricular arrhythmias in the rats with acute myocardial infarction.
      Further studies are needed to evaluate whether increasing vagal tonus during
      sympathetic activation may be valuable anti-arrhythmic strategy to prevent sudden
      death in patients with myocardial infarction and heart failure.

PMID- 17451679
TI  - New movements in neurofilament transport, turnover and disease.
AB  - Revealing the mechanisms by which neurofilament transport and turnover are
      regulated has proven difficult over the years but recent studies have given new
      insight into these processes. Mature neurofilament fibers may incorporate a
      fourth functional subunit, alpha-internexin, as new evidence suggests. Recent
      findings have made the role of phosphorylation in regulating neurofilament
      transport velocity controversial. Kinesin and dynein may transport neurofilaments
      in slow axonal transport as they have been found to associate with
      neurofilaments. Neurofilament transport and turnover rates may be reduced
      depending on the existing stationary neurofilament network. Finally, mutations in
      neurofilament light that have been linked to Charcot-Marie-Tooth disease as well
      as other neurofilament abnormalities in human disease are discussed.

PMID- 17451680
TI  - Proteins that associate with lamins: many faces, many functions.
AB  - Lamin-associated polypeptides (LAPs) comprise inner nuclear membrane proteins
      tightly associated with the peripheral lamin scaffold as well as proteins forming
      stable complexes with lamins in the nucleoplasm. The involvement of LAPs in a
      wide range of human diseases may be linked to an equally bewildering range of
      their functions, including sterol reduction, histone modification,
      transcriptional repression, and Smad- and beta-catenin signaling. Many LAPs are
      likely to be at the center of large multi-protein complexes, components of which
      may dictate their functions, and a few LAPs have defined enzymatic activities.
      Here we discuss the definition of LAPs, review their many binding partners,
      elaborate their functions in nuclear architecture, chromatin organization, gene
      expression and signaling, and describe what is currently known about their links
      to human disease.

PMID- 17451681
TI  - The tandem PDZ domains of syntenin promote cell invasion.
AB  - Syntenin is a tandem PDZ protein that has recently been shown to be overexpressed
      in several cancer cells and tissues, and that might play an active role in tumor
      cell invasion and metastasis. Here we show that overexpression of the tandem PDZ
      domains of syntenin in non-invasive cells is necessary and sufficient to
      stimulate these cells to invade a collagen I matrix, and this effect can be
      regulated by ligand binding to the PDZ domains. Furthermore, we show that
      syntenin-induced invasion requires signaling through ras, rho and PI3K/MAPK
      signaling pathways and involves changes in cell-cell adhesion. Inversely, when we
      used RNA interference to inhibit syntenin expression in different invasive cancer
      cell lines, we observed a drastically decreased ability of these cells to migrate
      and invade into collagen type I or Matrigel. RNAi-treated cells also show
      increased cell aggregation, indicating that syntenin is important for cell-cell
      adhesion in epithelial cells. Together, these results suggest that downregulation
      of syntenin by RNA interference could provide a means of inhibiting tumor
      invasion and possibly metastasis in different cancers, and point to syntenin as a
      potential cancer biomarker and drug target.

PMID- 17451682
TI  - HIF-1alpha expression in response to lipopolysaccaride mediates induction of
      hepatic inflammatory cytokine TNFalpha.
AB  - HIF-1alpha is a transcription factor that acts as a master regulator of gene
      expression induced by hypoxia. Recent studies have demonstrated that the potent
      inflammatory factor, lipopolysaccharide (LPS), can also activate HIF-1alpha in
      myeloid cells. However, the molecular mechanisms at the transcriptional level of
      HIF-1alpha induction by LPS remained undefined. Here, we investigated the
      regulatory mechanism of HIF-1alpha expression by LPS in hepatocytes and
      identified that LPS-induced HIF-1alpha mediate gene transcription of a typical
      inflammatory mediator, tumor-necrosis factor alpha (TNFalpha). Increased HIF
      1alpha gene expression by LPS was defined in a series of hepatic cell lines by RT
      PCR, Western blotting and promoter transactivation assay. The JNK signaling and c
      Jun activation were required to induce the HIF-1alpha gene transcription by LPS.
      The finding that a cascade transcriptional activation of distinct set of
      transcription factors, c-Jun and HIF-1alpha, in response to LPS stimulation
      associates with induction of TNFalpha gene transcription lends new insights into
      the functional mechanisms by which complex patterns of gene regulation on LPS
      derived HIF activation are achieved.

PMID- 17451683
TI  - Invertebrate lamins.
AB  - Lamins are the main component of the nuclear lamina and considered to be the
      ancestors of all intermediate filament proteins. They are localized mainly at the
      nuclear periphery where they form protein complexes with integral proteins of the
      nuclear inner membrane, transcriptional regulators, histones and chromatin
      modifiers. Studying lamins in invertebrate species has unique advantages
      including the smaller number of lamin genes in the invertebrate genomes and
      powerful genetic analyses in Caenorhabditis elegans and Drosophila melanogaster.
      These simpler nuclear lamina systems allow direct analyses of their structure and
      functions. Here we give an overview of recent advances in the field of
      invertebrate nuclear lamins with special emphasis on their evolution, assembly
      and functions.

PMID- 17451685
TI  - Striatal dopamine D2 receptors attenuate neuropathic hypersensitivity in the rat.
AB  - Earlier studies indicate that striatal dopamine D(2) receptors are involved in
      pain regulation in non-neuropathic conditions. We assessed whether striatal
      dopamine D(2) receptors contribute to pain regulation also in neuropathic
      conditions. The spared nerve injury model of neuropathy was induced by unilateral
      ligation of the tibial and common peroneal nerves in the rat. In awake nerve
      injured animals, pain-related withdrawal responses to calibrated monofilaments or
      noxious heating were attenuated following striatal administration of a dopamine
      D(2) receptor agonist quinpirole. Pain-related responses were attenuated only in
      the nerve-injured limb ipsilateral to the injection and in the midline (tail). In
      unoperated controls, striatal administration of quinpirole at an
      antihypersensitive dose did not influence withdrawal responses to mechanical
      stimulation. Attenuation of pain-related responses induced by striatal
      administration of quinpirole was reversed by intrathecal administration of a
      dopamine D(2) receptor antagonist (eticlopride) or a non-selective 5-HT receptor
      antagonist (methysergide), but not by an alpha(2)-adrenoceptor antagonist
      (atipamezole). In the rostroventromedial medulla of lightly anesthetized
      neuropathic animals, striatal administration of quinpirole significantly
      decreased the activity of presumably pronociceptive cells that are activated by
      noxious stimulation. The innocuous H-reflex in lightly anesthetized control
      animals was not suppressed by striatal administration of quinpirole at an
      antihypersensitive dose. The results indicate that striatal dopamine D(2)
      receptors attenuate neuropathic hypersensitivity. The antihypersensitive effect
      induced by striatal dopamine D(2) receptors in peripheral neuropathy involves
      suppression of impulse discharge of presumably pronociceptive neurons in the
      rostroventromedial medulla, and a descending influence acting on spinal 5-HT and
      dopamine D(2) receptors.

PMID- 17451684
TI  - Revisiting nestin expression in retinal progenitor cells in vitro and after
      transplantation in vivo.
AB  - The purpose of this study is to characterize the co-expression of nestin--a
      neuroectodermal stem cell and a reactive glial marker-with various mature retinal
      cell markers in retinal progenitor cells (RPCs) expanded in vitro, followed
      either by in vitro induction or subretinal transplantation. Rat RPCs derived from
      embryonic day (E) 17 rat retina were expanded in serum free defined culture, and
      induced to differentiate by all-trans retinoic acid (RA). Following induction,
      cells were stained for nestin in combination with retinal neuronal and glial
      markers. Cultured cells were collected for quantitative RT-PCR gene expression
      analysis prior to and after induction. In a second series, passage 2 RPCs were
      transplanted into the subretinal space of S334ter-3 retinal degeneration rats at
      postnatal day 28. After 1-4 weeks, sections through the transplant were double
      immunostained for nestin and various retinal specific neuronal markers. The
      cultured RPCs treated with RA exhibited nestin co-expression with various retinal
      specific markers, including protein kinase C alpha (PKC), neurofilament 200
      (NF200), cellular retinaldehyde binding protein (CRALBP), and rhodopsin.
      Following RA induction, quantitative RT-PCR analysis demonstrated downregulation
      of nestin, PAX-6, thy1.1, and PKCalpha, and upregulation of rhodopsin, glial
      fibrillary acidic protein (GFAP), and CrX. No nestin coexpression was observed
      with any of the retinal specific neuronal markers in RPC transplants in vivo
      except for some nestin-immunoreactivity overlapping with GFAP positive cells in
      the host retina. The role of nestin as a unique neural stem/progenitor cell
      marker should be reconsidered. Nestin expression during RPC maturation appears to
      be different in vitro versus in vivo.

PMID- 17451686
TI  - Abnormal expression of mu-crystallin in facioscapulohumeral muscular dystrophy.
AB  - To identify proteins expressed abnormally in facioscapulohumeral muscular
      dystrophy (FSHD), we extracted soluble proteins from deltoid muscle biopsies from
      unaffected control and FSHD patients and analyzed them using two-dimensional
      electrophoresis, mass spectrometry and immunoblotting. Muscles from patients with
      FSHD showed large increases over controls in a single soluble, 34 kDa protein
      (pI=5.08) identified by mass spectrometry and immunoblotting as mu-crystallin
      (CRYM). Soluble fractions of biopsies of several other myopathies and muscular
      dystrophies showed no appreciable increases in mu-crystallin. Mu-crystallin has
      thyroid hormone and NADPH binding activity and so may influence differentiation
      and oxidative stress responses, reported to be altered in FSHD. It is also linked
      to retinal and inner ear defects, common in FSHD, suggesting that its up
      regulation may play a specific and important role in pathogenesis of FSHD.

PMID- 17451687
TI  - Bilateral dorsal funicular lesions alter sensorimotor behaviour in rats.
AB  - Spinal cord injury models often involve damage to the corticospinal tract (CST)
      because of the functional importance of this pathway in humans. In rats, the main
      component of the CST travels in the dorsal funiculus and cannot be damaged
      without concurrent damage to overlying sensory fibers. To distinguish deficits
      due to the loss of CST from those due to sensory fiber damage, we bilaterally
      axotomized ascending sensory fibers in dorsal columns without CST damage in one
      group of rats (ascending sensory pathways, ASP) and compared the results to a
      group with damage to ascending sensory fibers with CST damage (ASP+CST). We
      assessed the ability of rats to perform a skilled reaching task and to walk over
      a horizontal ladder. We also measured the forces exerted on the ground (ground
      reaction forces, GRF) and limb contact patterns produced during overground
      locomotion. After ASP lesions alone, endpoint measurements of reaching success
      and footslip errors on the ladder showed transitory impairments, although
      detailed analysis revealed persistent deficits in skilled forelimb movements.
      ASP+CST lesions caused persistent deficits in reaching success and ladder
      footslips throughout the 8-week post-surgical period. Measurement of GRFs and
      limb timing during overground locomotion revealed differences in both groups at 8
      weeks post-surgery compared to pre-surgical values, but no differences between
      ASP and ASP+CST groups. These results emphasize the normal contribution of both
      ascending sensory axons and CST axons during skilled limb movements and support a
      role for ascending sensory information, but not descending CST input, during
      overground locomotion. These results also illustrate the value of using sensitive
      methods to reveal detailed behavioural changes after spinal injury.

PMID- 17451688
TI  - The role of small RNAs in abiotic stress.
AB  - It was recently discovered that plants respond to environmental stress not only
      with a specific gene expression programme at the mRNA and protein level but also
      small RNAs as response modulators play an important role. The small RNAs lead to
      cleavage or translational inhibition of mRNAs via complementary target sites.
      Different examples are described where small RNAs have been shown to be involved
      in stress responses. A link between hormonal action and small RNA activities has
      frequently been observed thus coupling exogenous factors with endogenous
      transmitters. Using the CDT-1 gene from the desiccation tolerant plant
      Craterostigma plantagineum as an example, it is discussed that generation of
      novel small RNAs could be an evolutionary pathway in plants to adapt to extreme
      environments.

PMID- 17451689
TI  - Crosstalk between xenobiotics metabolism and circadian clock.
AB  - Many aspects of physiology and behavior in organisms from bacteria to man are
      subjected to circadian regulation. Indeed, the major function of the circadian
      clock consists in the adaptation of physiology to daily environmental change and
      the accompanying stresses such as exposition to UV-light and food-contained toxic
      compounds. In this way, most aspects of xenobiotic detoxification are subjected
      to circadian regulation. These phenomena are now considered as the molecular
      basis for the time-dependence of drug toxicities and efficacy. However, there is
      now evidences that these toxic compounds can, in turn, regulate circadian gene
      expression and thus influence circadian rhythms. As food seems to be the major
      regulator of peripheral clock, the possibility that food-contained toxic
      compounds participate in the entrainment of the clock will be discussed.

PMID- 17451690
TI  - Different types of small nerve fibers in eutopic endometrium and myometrium in
      women with endometriosis.
AB  - OBJECTIVE: To investigate types of nerve fibers in endometrium and myometrium in
      women with endometriosis. DESIGN: Laboratory study using human tissue. SETTING:
      University-based laboratory. PATIENT(S): Women with and without endometriosis
      undergoing hysterectomy. INTERVENTION(S): Histologic sections of contiguous
      endometrial and myometrial tissues were prepared from hysterectomies performed on
      women with and without endometriosis. MAIN OUTCOME MEASURE(S): Types and density
      of nerve fibers in endometrium and myometrium in women with and without
      endometriosis were determined using a series of specific markers for neuronal
      structure and function: PGP9.5, NF, SP, CGRP, TH, VAChT, VIP, and NPY. RESULT(S):
      Nerve fibers stained with PGP9.5 and NF in endometrium and myometrium were
      significantly increased in women with endometriosis compared with women without
      endometriosis. Nerve fibers in the functional layer of endometrium in women with
      endometriosis were likely to be sensory C, a mixture of sensory A delta, sensory
      C, and adrenergic fibers in the basal layer of the endometrium, a mixture of
      sensory A delta, sensory C, adrenergic and cholinergic fibers in the myometrium.
      CONCLUSION(S): Increased nerve fiber density in endometrium and myometrium, and
      sensory C fibers and adrenergic nerve fibers in the endometrium in women with
      endometriosis may play an important role in the mechanisms of pain generation in
      this condition.

PMID- 17451691
TI  - Triggering of final oocyte maturation with gonadotropin-releasing hormone agonist
      or human chorionic gonadotropin. Live birth after frozen-thawed embryo
      replacement cycles.
AB  - OBJECTIVE: To report the outcome of frozen-thawed embryo replacement cycles after
      GnRH-agonist triggering of final oocyte maturation in the collecting cycle with
      GnRH-antagonist. DESIGN: Prospective, observational, multicentric clinical study.
      SETTING: Tertiary university-affiliated IVF centers. PATIENT(S): Patients under
      observation previously had been recruited into two concurrently performed,
      independent, randomized controlled trials (comparing hCG with GnRH-agonist for
      triggering final oocyte maturation in GnRH-antagonist multiple-dose protocols in
      normal responder patients) encompassing a total of 228 participants. Surplus
      embryos or oocytes at the pronuclear stage were cryopreserved in 53 patients
      after hCG administration and 32 patients after GnRH-agonist administration on the
      basis of patient choice, pronuclear/embryo availability, and local laws.
      INTERVENTION(S): Transfer of frozen-thawed embryos. MAIN OUTCOME MEASURE(S): Live
      birth rate. RESULT(S): Thirty-one and 23 patients after administration of hCG and
      GnRH-agonist, respectively, started a frozen-embryo replacement cycle by
      September 2005, with 25 and 16 patients eventually undergoing at least one frozen
      thawed ET. Live birth rate per ET was 18.5% (95% confidence interval [CI], 8.2
      36.7) and 30.0% (95% CI, 14.5-51.9) after hCG and GnRH-agonist triggering,
      respectively. Cumulative live birth rate per patient starting a frozen-embryo
      replacement cycle was 16.1% (95% CI, 7.1-32.6) and 26.1% (95% CI, 12.5-46.5) for
      hCG and GnRH-agonist, respectively. CONCLUSION(S): The likelihood of live birth
      in frozen-embryo replacement cycles after GnRH-agonist triggering of final oocyte
      maturation does not appear to be impaired.

PMID- 17451692
TI  - ACTH stimulation test in lean polycystic ovary syndrome patients with insulin
      resistance.
AB  - OBJECTIVE: To determine whether insulin resistance in nonobese polycystic ovarian
      syndrome (PCOS) patients is associated with a higher response to ACTH
      stimulation. DESIGN: Controlled prospective study. SETTING: University hospital
      ambulatory care unit. PATIENT(S): Twenty nonobese PCOS syndrome patients with
      insulin resistance and a body mass index-matched control group of 20 nonobese
      PCOS patients without insulin resistance. INTERVENTION(S): A 75-g oral glucose
      tolerance test and an ACTH stimulation test. MAIN OUTCOME MEASURE(S): Blood
      insulin and glucose levels after ingestion of 75 g oral glucose; blood
      androstenedione (A), 17(OH)-progesterone [17(OH)-P], free and total T, DHEAS, and
      progesterone (P) response to ACTH stimulation. RESULT(S): The proportional
      increases in the blood levels of total and free T, DHEAS, A, 17(OH)-P, and P
      following ACTH stimulation were similar in the two groups. Only the insulin area
      under the curve (AUC) values were significantly different among the two groups.
      The insulin AUC values were positively correlated to the free T blood levels and
      the homeostasis model assessment scores. CONCLUSION(S): Within the population of
      nonobese PCOS patients, insulin resistance is not associated with a more
      pronounced response to ACTH stimulation. The pathogenesis and management of PCOS
      in nonobese patients may be different from in obese patients.

PMID- 17451693
TI  - Unilateral laparoscopic ovarian diathermy in infertile women with clomiphene
      citrate-resistant polycystic ovary syndrome.
AB  - We evaluated the efficacy of unilateral versus bilateral laparoscopic ovarian
      diathermy in infertile women with clomiphene citrate-resistant polycystic ovary
      syndrome. Recall follow-up 18 to 48 months after laparoscopic ovarian diathermy
      showed that unilateral ovarian diathermy was as effective and long lasting as
      bilateral ovarian diathermy in the resumption of menstruation and pregnancy
      rates.

PMID- 17451694
TI  - Identification of a "cryptic mosaicism" involving at least four different small
      supernumerary marker chromosomes derived from chromosome 9 in a woman without
      reproductive success.
AB  - OBJECTIVE: To characterize the small supernumerary marker chromosomes (sSMCs)
      present in the female member of an infertile couple who has no further clinical
      symptoms. DESIGN: Case report. SETTING(S): Faculty of medicine and institute of
      human genetics and anthropology. PATIENT(S): A young, healthy, nonconsanguineous
      couple asked for genetic evaluation for infertility. INTERVENTION(S):
      Intracytoplasmic sperm injection, conventional and molecular cytogenetic
      analyses. MAIN OUTCOME MEASURE(S): We characterized the sSMCs present in a woman,
      who was a member of an infertile couple, by molecular cytogenetic techniques.
      RESULT(S): The G-banding technique showed that a marker chromosome was present in
      some of the examined cells describing the 47,XX,+mar[30]/46,XX[70] karyotype.
      Subsequently, using new fluorescence in situ hybridization (FISH) techniques,
      four distinguishable sSMCs (cryptic mosaicism), all derived from chromosome 9,
      were observed, including minute and ring chromosomes. This heterogeneity was
      impossible to detect by the conventional G-banding technique or conventional FISH
      technique that were used before the new FISH techniques (subcentromere-specific
      multicolor-FISH [subcenM-FISH]) and specific probe for the 9q12 band. In each
      metaphase with sSMCs, only one or two markers were observed. On the basis of the
      FISH analyses, the patient's karyotype was defined as 47,XX,+min(9)(:p12-
      >q12:)/47,XX,+min(9)(:p12-->q12::q12-->p12:)/47,XX,+r(9)(::p12-
      >q12::)/47,XX,+r(9)(::p12-->q12::p12-->q12::)x2/46,XX. CONCLUSION(S): The
      presence of sSMCs derived from chromosome 9 could influence the couple's
      infertility. The new subcenM-FISH techniques are very useful in the
      characterization of cryptic mosaicisms of marker chromosomes. Additionally, the
      hypothesis that the 9p12 chromosomal band is an euchromatic variant region
      without any phenotypic impact other than possible infertility is supported by
      this case study since the woman shows a normal phenotype.

PMID- 17451695
TI  - Sperm count and sperm motility in incidental high-grade varicocele.
AB  - One hundred twenty-four otherwise healthy men with suspected high-grade
      varicocele, comprised of 28 patients with grade 2 and 96 with grade 3 varicocele,
      were referred to us by their primary care providers to determine their exact
      grade so that they could be exempted from the compulsory armed force service if
      they had grade 3 varicocele. In the grade 2 and grade 3 groups, mean sperm
      concentration and mean sperm motility were 80.89 million per milliliter (SD,
      38.98 million/mL; median, 74.5 million/mL; range, 22-210 million/mL) and 78.77
      million per milliliter (SD, 41.34 million/mL; median, 77 million/mL; range, 0-223
      million/mL) and 58.39% (SD, 13.7%; median, 60%; range, 22-75%) and 60.31% (SD,
      16.93%; median 65%; range, 0-80%), respectively, with no statistically
      significant differences between the two groups, no patient with infertility as a
      complaint during a 20-month period, and no patient with sperm concentrations of
      <20 million/mL, but with six patients with sperm motilities <50%. In summary, by
      far the great majority of patients with high grade varicocele have more than
      normal sperm output. Higher grades of varicocele are not associated with more
      pronounced deleterious effects on sperm concentration and percentage motility.
      Incidentally diagnosed high-grade varicocele is not a progressive condition, and
      almost all patients retain normal semen quality, at least over a period of 20
      months.

PMID- 17451696
TI  - Localization of single-stranded DNA in human sperm nuclei.
AB  - OBJECTIVE: To localize foci of single-stranded (ss) DNA in sperm nuclei of
      fertile and infertile men. DESIGN: Prospective, observational study. SETTING:
      University infertility clinic. PATIENT(S): Semen samples from 12 consecutive
      asthenoteratospermic men presenting for infertility evaluation and 5 consecutive
      fertile men presenting for vasectomy. INTERVENTION(S): Semen analysis, semen
      processing, and immunocytochemistry using an antibody targeting ssDNA. MAIN
      OUTCOME MEASURE(S): Sperm nuclear ssDNA immunostaining pattern in whole and
      processed semen samples. RESULT(S): Immunocytochemistry (using ssDNA antibody)
      demonstrated one of two sperm nuclear staining patterns: [1] faint punctated
      staining, and [2] diffuse nuclear staining. Infertile men had a higher proportion
      of spermatozoa exhibiting diffuse ssDNA staining than did fertile men (52 +/- 19
      vs. 14 +/- 13, respectively). The proportion of spermatozoa exhibiting diffuse
      ssDNA staining was significantly higher in whole compared with processed semen.
      Positive (DNAse-treated nuclei) and negative controls (S1 nuclease-treated
      nuclei) were obtained to validate the specificity of the antibody. CONCLUSION(S):
      Human sperm nuclei generally exhibit discrete (presumably peripheral) foci of
      ssDNA. The data also show that infertile men have a higher proportion of sperm
      nuclei with diffuse areas of ssDNA than do fertile men, and suggest that
      spermatozoa with diffuse nuclear staining are abnormal.

PMID- 17451697
TI  - Day-3 embryo morphology predicts euploidy among older subjects.
AB  - OBJECTIVE: To evaluate whether day-3 embryo morphology predicts euploidy. DESIGN:
      Retrospective. SETTING: Private IVF center. PATIENT(S): Subjects (n = 144)
      undergoing in vitro fertilization and preimplantation genetic diagnosis (PGD).
      INTERVENTION(S): Translate day-3 embryo characteristics into a standardized
      score. MAIN OUTCOME MEASURE(S): Day-3 embryo morphology score and PGD
      fluorescence in situ hybridization results for chromosomes: 13, 15, 16, 17, 18,
      21, 22, X, and Y. RESULT(S): Of 1,043 biopsied blastomeres, 67% (n = 696) were
      chromosomally abnormal. Women with advanced maternal age (AMA) were 1.3 times
      more likely to have chromosomal errors (95% CI 1.1-1.4) than younger subjects
      (<38 years old). Morphology predicted PGD results in the AMA group (n = 553), but
      not in younger women. Fragmentation predicted euploidy in both the younger and
      the AMA group, but cell number did not. CONCLUSION(S): Day-3 embryo morphology
      selects for euploidy among AMA subjects but not among younger women who may have
      other factors responsible for embryo dysmorphism. However, cellular fragmentation
      is a sensitive proxy for selecting chromosomally normal embryos in both age
      groups. It is unclear that PGD-aneuploidy screening is a better tool for
      selecting which embryos to transfer than the standard approach of using day-3
      embryo features, particularly among older women, a group for whom this technology
      is targeted.

PMID- 17451698
TI  - A 15-year-old boy with an esophageal pyogenic granuloma and subsequent Barrett's
      esophagus (with videos).

PMID- 17451699
TI  - Gastric relapse of plasma-cell myeloma after stem-cell transplantation.

PMID- 17451700
TI  - Successful endoscopic management of gastrojejunal anastomotic strictures after
      Roux-en-Y gastric bypass.
AB  - BACKGROUND: Roux-en-Y gastric bypass is the most frequently performed bariatric
      surgery for morbid obesity. Gastrojejunal anastomotic strictures are a relatively
      frequent postoperative complication. OBJECTIVE: To evaluate the clinical outcomes
      and therapeutic response to through-the-scope balloon dilation performed to treat
      anastomotic strictures after Roux-en-Y gastric bypass surgery. DESIGN: Single
      center, retrospective study. SETTING: Academic medical center. PATIENTS: Between
      1997 and 2005, 801 patients with morbid obesity underwent Roux-en-Y gastric
      bypass surgery at our institution. MAIN OUTCOME MEASUREMENTS: The development of
      an anastomotic stricture after Roux-en-Y gastric bypass surgery. The response to
      through-the-scope balloon dilation after diagnosis. RESULTS: Forty-three of 801
      patients (5.4%) developed an anastomotic stricture (26 of 294 open surgeries
      [8.8%]; 17 of 507 laparoscopic surgeries [3.4%]; P < .001). Strictures were
      dilated to 15.5 +/- 0.4 mm. There were no perforations or clinically significant
      bleeding after dilation; 93% of the strictures were successfully managed with 1
      or 2 endoscopic sessions. Dilation to at least 15 mm did not affect weight loss
      at 1 year when compared with the group without a stricture (percentage excess
      weight loss: stricture group, 76%; no stricture group, 74%). LIMITATIONS: Single
      center, retrospective study. CONCLUSIONS: Endoscopic balloon dilation is a safe
      and effective method for the management of gastrojejunostomy strictures after
      Roux-en-Y gastric bypass. Dilation to at least 15 mm is safe and decreases the
      need for further endoscopic dilation.

PMID- 17451701
TI  - Endoscopic pyloroplasty with full-thickness transgastric and transduodenal
      myotomy with sutured closure.
AB  - BACKGROUND: Pyloroplasty with myotomy and sutured closure is a surgical treatment
      for gastric outlet obstruction. It has not been previously performed at flexible
      endoscopy. OBJECTIVE: To develop and test a method for performing a sutured
      pyloroplasty at flexible endoscopy. DESIGN: A Heinicke-Miculicz pyloroplasty was
      performed, forming a linear myotomy through the pylorus from the gastric side
      into the duodenal bulb. This was subsequently sutured transversely to increase
      the opening. The operation was performed in 3 nonsurvival studies in pigs. The
      safety and the efficacy was then studied in 7 animals followed for up to 4 weeks
      after the procedure. SETTING: The studies were performed in experimental surgical
      units in Gothenburg, Sweden, and London, UK. INTERVENTIONS: A linear needle-knife
      incision was made through the pylorus; full-thickness sutures, by using a new T
      tag and polypropylene thread suturing system through a flexible gastroscope, were
      placed to close the incision transversely. In 2 pigs, the prepyloric bulge was
      excised before the pyloroplasty. RESULTS: Pyloroplasty was readily accomplished
      at flexible endoscopy in the 3 nonsurvival studies. Six of 7 pigs that survived
      in this study for periods of 7 to 28 days, recovered well, without complications.
      One pig (with bulge removal) developed gastric retention. The pyloric opening was
      increased; it was then easy to enter the duodenum at follow-up endoscopy.
      LIMITATIONS: This method has yet to be studied clinically. CONCLUSIONS:
      Pyloroplasty with full-thickness pyloromyotomy and transverse closure of a linear
      myotomy was accomplished by using a simple flexible endosurgical technique to
      test a new flexible suturing system.

PMID- 17451702
TI  - Emergent band ligation for cardiac variceal bleeding: serial endoscopic images.

PMID- 17451703
TI  - Celiac disease: in vivo diagnosis by confocal endomicroscopy.

PMID- 17451704
TI  - Are dysplasia and colorectal cancer endoscopically visible in patients with
      ulcerative colitis?
AB  - BACKGROUND: Dysplasia and colorectal cancer (CRC) in ulcerative colitis (UC)
      develop via pathways distinct from sporadic CRC and may occur in flat mucosa
      indistinct from surrounding tissue. Surveillance guidelines, therefore, have
      emphasized the ;roach of periodic endoscopic examinations and systematic random
      biopsies of involved mucosa. Given the imperfect nature of this random approach,
      recent work has focused on improved surveillance techniques and suggests that
      neoplasia is endoscopically visible in many patients. OBJECTIVE: To assess the
      endoscopic visibility of dysplasia and CRC in UC. DESIGN: This was a
      retrospective review that used the University of Chicago Inflammatory Bowel
      Disease Registry and the clinical administrative database. All cases of dysplasia
      or CRC in UC between November 1994 and October 2004 were identified. The approach
      to surveillance in these patients included both random biopsies at approximately
      10-cm intervals throughout the involved colon and directed biopsies of polypoid
      lesions, masses, strictures, or irregular mucosa distinct from surrounding
      inflamed tissue. Findings on endoscopy were compared with pathologic findings
      from biopsy or surgical specimens. Visible dysplasia was defined as a lesion
      reported by the endoscopist that led to directed biopsy and that was confirmed by
      pathology. Invisible dysplasia was defined as dysplasia diagnosed on pathology
      but not described on endoscopy. Per-lesion and per-patient sensitivities were
      determined. SETTING: Tertiary referral center. PATIENTS: Database of patients
      with inflammatory bowel disease seen at the University of Chicago. MAIN OUTCOME
      MEASUREMENTS: Endoscopically visible neoplasia. RESULTS: In this database, there
      were 1339 surveillance examinations in 622 patients with UC. Forty-six patients
      were found to have dysplasia or CRC at a median age of 48 years and with median
      duration of disease of 20 years. Of these patients, 77% had pancolitis, 21% had
      left-sided colitis, and 2% had proctitis. These patients had 128 surveillance
      examinations (median 3 per patient; range, 1-9 per patient), and, in 51
      examinations, 75 separate dysplastic or cancerous lesions were identified (mean,
      1.6 lesions per patient; standard deviation, 1.3). Thirty-eight of 65 dysplastic
      lesions (58.5%) and 8 of 10 cancers (80.0%) were visible to the endoscopist as 23
      polyps and masses, 1 stricture, and 22 irregular mucosa. The per-patient
      sensitivities for dysplasia and for cancer were 71.8% and 100%, respectively. The
      overall per-lesion and per-patient sensitivities were 61.3% and 76.1%,
      respectively. LIMITATIONS: Retrospective review of clinical databases and medical
      records. CONCLUSIONS: Dysplasia and cancer in UC are endoscopically visible in
      most patients and may be reliably identified during scheduled examinations.
      Future surveillance guidelines should incorporate this information.

PMID- 17451705
TI  - Salmonella enterocolitis and hemorrhagic shock.

PMID- 17451706
TI  - Gastric outlet obstruction as a complication of argon plasma coagulation for
      watermelon stomach.

PMID- 17451707
TI  - Splenic artery embolization and infarction after cyanoacrylate injection for
      esophageal varices.

PMID- 17451708
TI  - Intraductal US in evaluation of biliary strictures without a mass lesion on CT
      scan or magnetic resonance imaging: significance of focal wall thickening and
      extrinsic compression at the stricture site.
AB  - BACKGROUND AND OBJECTIVE: The clinical utility of intraductal US (IDUS) for
      evaluating biliary strictures has been limited because of a lack of easily
      recognized morphologic criteria to distinguish benign and malignant strictures.
      We studied the clinical value of 2 easily assessed IDUS findings: wall thickness
      and extrinsic compression at the stricture site. DESIGN AND SETTING: A
      retrospective, single-center study. PATIENTS AND METHODS: Forty-five patients
      without an identifiable mass on CT/magnetic resonance imaging, who underwent
      ERCP/IDUS for evaluation of biliary strictures were studied. IDUS pictures were
      reviewed specifically to measure wall thickness and to look for extrinsic
      compression at the stricture site. MAIN OUTCOME MEASUREMENTS AND RESULTS: The
      mean age of the patients was 64.2+/-13.3 years. Thirty patients had jaundice at
      presentation, and in 15 patients a stricture was suspected on imaging. The mean
      length of biliary strictures was 15.1+/-7.8 mm. Strictures were distal (distal
      common bile duct) in 25 patients and proximal (mid/proximal common bile duct or
      common hepatic duct) in 20 patients. Fourteen strictures were finally diagnosed
      to be malignant. Strictures in 20 patients were caused by extrinsic compression,
      and tissue diagnosis was readily obtained by EUS-FNA in all these patients. Of 25
      strictures without extrinsic compression, 6 were malignant (wall thickness 9-16
      mm) and 19 were benign (wall thickness<or=9 mm). Bile duct wall thickness<or=7 mm
      at the stricture site, in the absence of extrinsic compression, had a negative
      predictive value of 100% for excluding malignancy in this cohort. LIMITATIONS:
      Retrospective study and relatively small number of patients. CONCLUSIONS:
      Evaluation of wall thickness and the presence of extrinsic compression at the
      site of biliary strictures by IDUS can help in further management of these
      patients.

PMID- 17451709
TI  - Wireless capsule endoscopy in the diagnosis of helminthiasis.

PMID- 17451710
TI  - Cystic lesion of the pancreas.

PMID- 17451711
TI  - Diagnostic value of micro-CT in comparison with histology in the qualitative
      assessment of historical human postcranial bone pathologies.
AB  - Micro-computed tomography (muCT) is of great interest for palaeopathological
      examination because it is less invasive than histology. This study evaluates the
      diagnostic value of muCT for postcranial macerated bones. We investigated five
      specimens (osteomyelitis, tuberculosis, trauma, osteosarcoma and hypertrophic
      osteoarthropathy) of a pathology reference series by muCT and polarised light
      microscopy. The 3D muCT images allow an easy orientation within the specimen.
      Surface structures, thickness, continuity of the cortex and number, thickness and
      orientation of the trabeculae can be evaluated. The high number of muCT slices
      helps to choose the most interesting areas for further investigations. Grey value
      images display the degree of mineralisation. Yet, the differentiation between
      woven and lamellar bone is only possible using polarised light microscopy. muCT
      is a tool of high value for the examination of postcranial bone disorders. It
      cannot replace histological examinations completely because it cannot assess the
      bone quality (woven or lamellar). For the choice of the optimal location where
      slices for the microscopic investigation are later cut in heterogeneous samples,
      muCT is very useful. Therefore, we suggest performing the muCT examination first,
      followed by histology if necessary.

PMID- 17451712
TI  - "Current thoughts" in electrosurgery.
AB  - The ongoing desire to improve hemostasis and efficiency during surgery is
      manifested in the rapid development of electrosurgical technology. These changes
      have brought about a wide variety of devices available to the practicing surgeon
      during both open and endoscopic cases. Depending on the instrument chosen,
      various clinical effects ranging from simple coagulation to the sealing of large
      vascular bundles are obtained. However potential pitfalls or complications also
      exist. A thorough understanding of the pros and cons of these technological
      advancements can improve the operative experience for both surgeon and patient.

PMID- 17451713
TI  - Access to sexual and reproductive health services: rights, priorities,
      commitments and actions.

PMID- 17451714
TI  - Sexually transmitted infections: key issues for clinical practice.

PMID- 17451715
TI  - Overcoming barriers to the eradication of cervical cancer: women's health and
      rights.

PMID- 17451716
TI  - Measuring nursing competence: development of a self-assessment tool for general
      nurses across Europe.
AB  - In response to the global challenge of providing and delivering effective health
      care, the aim of the European Healthcare Training and Accreditation Network
      project is to work towards improving the transparency of European Union (EU)
      nurse workforce qualifications, competence, skills, experience and culture.
      Currently, there is no detailed or tangible method available for comparison,
      which is perceived as an obstacle to EU nurse workforce mobility. OBJECTIVES:
      Clearly, this is an important issue that needs to be addressed. Accordingly, this
      paper reports on the development and psychometric testing of a nurse competence
      self-assessment questionnaire tool, with the aim of contributing to and enhancing
      the transparency of nurse competence and ultimately facilitating greater nurse
      workforce mobility across the EU. SETTINGS: The project comprises a partnership
      led by a school of nursing in London, operating in collaboration with nursing and
      other academics from institutions in Belgium, Germany, Greece and Spain. METHODS:
      Subsequent to a review of literature on nurse competence, a 108 item, post
      registration nurse competence self-assessment questionnaire was developed. It
      elicits information indicating nurse's self-assessment of their competence in the
      EU country where they trained and qualified and are currently still employed.
      Responses invite a self-reported frequency of nursing function, this being
      recommended as the most accurate and least threatening way of assessing
      competency. During the development process, the questionnaire, constructed from
      EU countries' competence frameworks, was deemed to be relevant to the measurement
      of nurse competence by a group of professors of nursing, senior nurse educators,
      senior nurse managers and other academics thus attesting to the questionnaire's
      content validity. PARTICIPANTS: A convenience sample of 588 post-registration,
      generalist nurses from medical or surgical inpatient wards/units were surveyed
      from acute hospitals in the partner countries (UK n=100, Belgium n=113, Greece
      n=95, Germany n=150, Spain n=130). RESULTS: Psychometric testing, as expressed by
      Cronbach's alpha values and by principal component factor analysis, suggests that
      the questionnaire has an acceptable degree of reliability, construct validity and
      further supports the content validity. CONCLUSION: In the future, it is envisaged
      that nurses will be able to utilise the questionnaire to make more informed
      judgement about the match between their competence and that required of a
      possible host country. Employers will be able to detect any differences in the
      required competence levels of potential employees, thus facilitating greater EU
      nurse workforce mobility.

PMID- 17451717
TI  - Sexual reproduction facilitates the adaptation of parasites to antagonistic host
      environments: Evidence from empirical study in the wheat-Mycosphaerella
      graminicola system.
AB  - Most eukaryotes use sexual reproduction to transmit genetic information from
      generation to generation despite the advantages offered by asexual reproduction.
      One theory to explain the origin and maintenance of sexual reproduction
      hypothesises that sexual recombination generates genetic variation that allows
      faster adaptation to fluctuating and/or stressful environments. We used a
      combination of ecological, molecular genetic, statistical and experimental
      evolution approaches to test this hypothesis in an agricultural plant-pathogen
      system. We inoculated wheat hosts with 10 strains of the fungal pathogen
      Mycosphaerella graminicola in a field experiment and estimated the contributions
      of sexual reproduction, asexual reproduction and immigration to the genetic
      composition of fungal populations sampled from moderately resistant and
      susceptible hosts through the course of an epidemic cycle. We found that a
      significant proportion of the M. graminicola population in the late phase of the
      epidemic originated from sexual reproduction among isolates that had been
      introduced into the field plots at the beginning of the epidemic. Recombinants
      were recovered at a higher frequency on the moderately resistant plant host
      Madsen than on the susceptible host Stephens. By the end of the growing season,
      we estimated that approximately 13% of the strains sampled from the resistant
      host were recombinants, compared with 9% in the samples collected from the
      susceptible host. We also found that pathogen strains originating from the
      resistant cultivar displayed higher levels of fitness, virulence and fungicide
      tolerance than those originating from the susceptible cultivar. Our results
      provide empirical support for the hypothesis that sexual reproduction facilitates
      the evolution of parasites to overcome host resistance.

PMID- 17451718
TI  - Expression and purification of an active cysteine protease of Haemonchus
      contortus using Caenorhabditis elegans.
AB  - Many proteolytic enzymes of parasitic nematodes have been identified as possible
      targets of control. Testing these as vaccine or drug targets is often difficult
      due to the problems of expressing proteases in a correctly folded, active form in
      standard expression systems. In an effort to overcome these difficulties we have
      tested Caenorhabditis elegans as an expression system for a Haemonchus contortus
      cathepsin L cysteine protease, Hc-CPL-1. Recombinant Hc-CPL-1 with a
      polyhistidine tag added to the C-terminal was expressed in an active and
      glycosylated form in C. elegans. Optimal expression was obtained expressing Hc
      cpl-1 under control of the promoter of the homologous C. elegans cpl-1 gene. The
      recombinant protein was purified from liquid cultures by nickel chelation
      chromatography in sufficient amounts for vaccination studies to be carried out.
      This study provides proof of principle that active, post-translationally modified
      parasitic nematode proteases can be expressed in C. elegans and this approach can
      be extended for expression of known protective antigens.

PMID- 17451719
TI  - Resolution of the species problem in African trypanosomes.
AB  - There is a general assumption that eukaryote species are demarcated by
      morphological or genetic discontinuities. This stems from the idea that species
      are defined by the ability of individuals to mate and produce viable progeny. At
      the microscopic level, where organisms often proliferate more by asexual than
      sexual reproduction, this tidy classification system breaks down and species
      definition becomes messy and problematic. The dearth of morphological characters
      to distinguish microbial species has led to the widespread application of
      molecular methods for identification. As well as providing molecular markers for
      species identification, gene sequencing has generated the data for accurate
      estimation of relatedness between different populations of microbes. This has led
      to recognition of conflicts between current taxonomic designations and
      phylogenetic placement. In the case of microbial pathogens, the extent to which
      taxonomy has been driven by utilitarian rather than biological considerations has
      been made explicit by molecular phylogenetic analysis. These issues are discussed
      with reference to the taxonomy of the African trypanosomes, where pathogenicity,
      host range and distribution have been influential in the designation of species
      and subspecies. Effectively, the taxonomic units recognised are those that are
      meaningful in terms of human or animal disease. The underlying genetic
      differences separating the currently recognised trypanosome taxa are not
      consistent, ranging from genome-wide divergence to presence/absence of a single
      gene. Nevertheless, if even a minor genetic difference reflects adaptation to a
      particular parasitic niche, for example, in Trypanosoma brucei rhodesiense, the
      presence of a single gene conferring the ability to infect humans, then it can
      prove useful as an identification tag for the taxon occupying that niche. Thus,
      the species problem can be resolved by bringing together considerations of
      utility, genetic difference and adaptation.

PMID- 17451720
TI  - Liquid chromatographic method development for steroids determination (corticoids
      and anabolics). Application to animal feed samples.
AB  - A LC isocratic separation study of a complex mixture containing 18 steroids
      (corticoids and anabolics), used potentially as growth promoters, was carried
      out. For this purpose, using a Hypersil ODS column at controlled temperature,
      mobile phases (from binary to quaternary) prepared from water and MeOH, ACN or
      THF as organic modifiers and UV detection at 245 nm, were employed
      (dehydroepiandrosterone was detected at 200 nm). The optimum separation was
      achieved using water/acetonitrile (65:35, v/v) as mobile phase at 30 degrees C,
      allowing the separation of 16 out of 18 steroids in about 30 min. The retention
      scale using optimized binary mobile phases was related with steroids
      hydrophobicity and structure, allowing a classification into three groups for
      these compounds. To improve the separation several alkyl-silica packings were
      tested: Type A (Lichrospher C8) and Type B (Luna C18, Kromasil C18, Purospher C18
      and Synergy C12). Taking into account resolution, number of separated compounds
      and run time analysis the Hypersil column was selected as the best choice for
      further applications. Calibration graphs were obtained using fluorocortisone,
      fluoxymesterone or methylprednisolone as internal standard. The optimized
      separation was applied to the analysis of piglet feed samples spiked with
      steroids. The sample preparation process included solvent extraction using
      diethyleter and solid phase extraction using silica cartridges. The recoveries
      were in the range 70-92%. Decision limits and detection capability were in the
      range 34-198 and 41-249 microg/kg, respectively. Repeatability was also
      evaluated.

PMID- 17451721
TI  - Determination of the acid/base properties of MgY and NH4Y molecular sieves by
      inverse gas chromatography.
AB  - The surface characterization of MgY and NH(4)Y zeolites was performed using
      inverse gas chromatography (IGC). The adsorption thermodynamic parameters (the
      standard enthalpy (DeltaH degrees ), standard entropy change (DeltaS degrees ),
      and free energy change of adsorption (DeltaG degrees ), the dispersive component
      of the surface free energies (gamma(S)(d)), and the acid-base character of the
      surface of MgY and NH(4)Y zeolites were estimated using the retention time of
      different non-polar and polar probes at infinite dilution region. The specific
      free energy of adsorption (DeltaG(sp)), the specific enthalpy of adsorption
      (DeltaH(sp)), and the specific entropy of adsorption (DeltaS(sp)) of polar probes
      on MgY and NH(4)Y zeolites were determined. The values of the DeltaH(sp) were
      correlated with both the donor and acceptor numbers of the probes to quantify the
      acidic K(A) and the basic K(D) parameters of the zeolite surfaces. The values
      obtained for the K(A) and K(D) parameters indicated a basic character for the
      surface of MgY and NH(4)Y zeolites.

PMID- 17451722
TI  - Adsorption of monoclonal antibody variants on analytical cation-exchange resin.
AB  - Monoclonal antibody (MAb) variants differing by one or two C-terminal lysine
      residues can be separated by cation-exchange chromatography due to the difference
      in their charge distribution. The adsorption of the three MAb variants on a weak
      cation-exchange resin was characterized using directly the raw mixture in spite
      of the presence of some impurities. The effects of both, pH and eluent salt
      concentration, on the adsorption isotherm were investigated. Under certain
      experimental conditions distorted peak shapes and even peak doubling for single
      variant injections were obtained, in addition to unexpectedly long retention
      times. These observations were explained based on equilibrium theory. The
      separation of the MAb variants was designed for an isocratic and a linear salt
      gradient operation. The corresponding optimal values of pH and salt concentration
      were determined. The use of salt gradients not only allows reducing the process
      time and increasing enrichment of the variants, but also leads to some loss in
      purity. A baseline separation could be obtained under isocratic and strongly
      adsorbing conditions at pH 6.3. A lumped kinetic model and a procedure for
      estimating the corresponding parameters were developed and validated by
      comparison with experimental elution chromatograms in a wide range of operating
      conditions.

PMID- 17451723
TI  - Use of porous graphitic carbon for the analysis of nitrate ester, nitramine and
      nitroaromatic explosives and by-products by liquid chromatography-atmospheric
      pressure chemical ionisation-mass spectrometry.
AB  - A new LC/MS method was developed for the analysis of sixteen different analytes
      including the most common organic explosives encountered in forensic
      investigations. The separation was achieved using a porous graphitic carbon (PGC)
      column with a binary gradient elution. Molecular modeling suggested a possible
      interpretation for the elution order of explosive compounds on PGC. The
      introduction of ammonium formate in the mobile phase resulted in the formation of
      characteristic adduct ions thus enhancing the mass spectrometric detection of
      nitrate ester and nitramine compounds. Atmospheric pressure chemical ionization
      (APCI) and electrospray ionization (ESI) were compared in terms of sensitivity.
      The final LC/APCI-MS method allowed easy identification of investigated compounds
      with limits of detection ranging from 0.04 to 1.06 ng/microl. The analysis of
      simulated forensic samples confirmed the performance of the method.

PMID- 17451724
TI  - A macrocyclic polyamine as an anion receptor in the capillary
      electrochromatographic separation of carbohydrates.
AB  - An analytical approach of the 32-membered macrocyclic polyamine,
      1,5,9,13,17,21,25,29-octaazacyclodotriacontane ([32]ane-N8) was described for the
      capillary electrochromatographic (CEC) separation of derivatized mono- and
      disaccharides. The column displayed reversal electroosmotic flow (EOF) at pH
      below 7.0, while a cathodic EOF was shown at pH above 7.0. The reductive
      amination of saccharides was carried out with p-aminobenzoic acid. Some
      parameters that affect the CEC separations were investigated. Several competitive
      ligands, such as Tris, EDTA and phosphate were also examined for the effect on
      the performance. We achieved a complete separation of all compounds as well as
      the excess derivatizing agent by using borate buffer (pH 9.0) in a mode of
      concentration gradient (60 mM inlet side and 70 mM outlet side). The relative
      standard deviation of the retention time measured for each sample was less than
      4% in six continuous runs, suggesting that the bonded phase along with the
      gradient formed inside the column was quite stable. With the mixing modes of
      anion coordination, anion exchange, and shape discrimination, the interaction
      adequately accomplishes the separation of carbohydrates which are epimers or have
      different glycosidic linkage, although the electrophoretic migration is also
      involved in the separation mechanism.

PMID- 17451725
TI  - Affinity chromatography with immobilized DNA stationary phase for biological
      fingerprinting analysis of traditional Chinese medicines.
AB  - A stationary phase for high performance affinity chromatography with
      immobilization of DNA onto silica gel was prepared and characterized. The effect
      of the ionic strength, concentration of Mg2+, EDTA and CH3CN in the mobile phase
      on the retention of alkaloids were investigated. With this stationary phase,
      biological fingerprinting analysis of traditional Chinese medicines (TCMs) Coptis
      chinensis Franch and Rheum palmatum L. was performed with both one-dimensional (1
      D) and two-dimensional (2-D) chromatography. The 1-D chromatography was performed
      with isocratic and gradient elution and 2-D chromatography was developed with
      immobilized DNA column combined with silica monolithic ODS column. It was found
      that 7 compounds in Coptis chinensis Franch including berberine, palmatine and
      jatrorrhizine, 14 compounds in Rheum palmatum L. including aloe-emodin, rhein,
      emodin, chrysophannol-8-O-glucophranoside and physionl-8-O-glucophranoside were
      active in binding to the immobilized DNA.

PMID- 17451726
TI  - Determination of trazodone in urine and pharmaceuticals using micellar liquid
      chromatography with fluorescence detection.
AB  - A simple and reliable liquid chromatographic procedure is described for the
      determination of trazodone in pharmaceutical formulations and urine samples. The
      optimized procedure uses fluorimetric detection, a C18 column and a micellar
      mobile phase of sodium dodecyl sulfate (SDS) and 1-butanol. The mobile phase
      selected for use was 0.2M SDS and 8% 1-butanol fixed at pH 3 with phosphate
      buffer. The total analysis time was 10 min. For the analysis of urine samples,
      one great advantage of the method is that no extraction step is required. The
      quantification limit was 9.5 ng mL(-1), ensuring the analysis of the drug in
      biological fluids. The procedure shows good accuracy, repeatability and
      selectivity. Repeatability and intermediate precision were tested for several
      concentrations of the drug. Good claim percentages were obtained in the analysis
      of pharmaceutical formulations. Calibration repeatability in urine matrix was
      also studied in the 0.06-22.4 microg mL(-1) range. Good recoveries were obtained
      from spiked urine samples. No interferences from common additives frequently
      administered with trazodone or from endogenous compounds in urine samples were
      found. The results show that the procedure is suitable for routine analysis of
      the drug.

PMID- 17451727
TI  - Enhanced stability of short- and long-chain diselenide self-assembled monolayers
      on gold probed by electrochemistry, spectroscopy, and microscopy.
AB  - Well-ordered, compact, self-assembled monolayers (SAMs) of hexyl and dodecyl
      diselenides have been formed on oriented (111) gold surfaces. Monolayer formation
      has been effected by adsorption from neat diselenides as well as millimolar
      solutions of diselenides in alcohol. The monolayer formation is confirmed using
      electrochemical quartz crystal microbalance studies. The stability and
      permeability of the monolayers at various temperatures have been probed using
      reflection absorption infrared spectroscopy (RAIRS) and electrochemistry. The
      RAIRS studies in the dry state show the formation of highly ordered, compact
      structures when adsorbed from neat compounds compared to the monolayers adsorbed
      in the presence of alcohol. The monolayers adsorbed from neat diselenide are
      quite stable as a function of temperature irrespective of the chain length. The
      electrochemical studies based on the blocking behavior of the monolayers toward
      electron transfer between a diffusing species and the electrode surface reflect
      the stability and the compactness of the structure. The results point out that
      the presence of solvent molecules during the SAM formation hinders the
      organization of the monolayer structure, especially in the case of short-chain
      diselenide monolayers.

PMID- 17451728
TI  - Electrokinetic effect and surface free energy behavior in the adsorption process
      of a reactive dye onto Leacril pretreated with polyethyleneimine ion.
AB  - In a previous paper, we studied the adsorption of a polyelectrolyte,
      polyethyleneimine ion (PEI), onto Leacril in order to increase the amount of the
      reactive dye Remazol Brilliant Blue R (RBBR) taken up by these fibers. We
      observed that this polycation changes the fibers zeta potential sign at low
      concentration, ca. 0.03 g/L, and thus the RBBR adsorption onto Leacril is
      improved when implementing the PEI treatment. The aim of this work is to study
      the PEI effect related to the amount of dye adsorbed by Leacril. For this
      purpose, we present data on streaming potential, adsorption isotherms, and
      surface free energy component determination as a function of the PEI
      concentration used in the pretreatment, as well as a function of the RBBR
      concentration used in the dyeing solutions. Adsorption experimental results show
      that the amount of RBBR taken by the fibers increases with the PEI concentration
      used in the pretreatment, and this effect becomes significant at higher
      concentrations of RBBR solution. The zeta potential increases to positive values
      in the range of low concentrations of dye solution when Leacril fibers have been
      pretreated with the polyelectrolyte. From surface free energy component
      determinations it is worth noting that the electron-donor component, gamma(-),
      decreases with the RBBR concentration in the treatment. The results we have
      obtained suggest that the interaction between the amine group of the PEI
      previously adsorbed and the reactive beta-sulfato-ethysulfonyl group of the dye
      can be responsible for the improvement in dye uptake.

PMID- 17451729
TI  - Formation of complex Langmuir and Langmuir-Blodgett films of water soluble
      rosebengal.
AB  - This communication reports the formation of complex Langmuir monolayer at the air
      water interface by charge transfer types of interaction with the water soluble N
      cetyl N,N,N-trimethyl ammonium bromide (CTAB) molecules doped with rosebengal
      (RB), with the stearic acid (SA) molecules of a preformed SA Langmuir monolayer.
      The reaction kinetics of the formation of RB-CTAB-SA complex monolayer was
      monitored by observing the increase in surface pressure with time while the
      barrier was kept fixed. Completion of interaction kinetics was confirmed by FTIR
      study. This complex Langmuir films at the air-water interface was transferred
      onto solid substrates at a desired surface pressure to form multilayered Langmuir
      Blodgett films. Spectroscopic characterizations reveal some molecular level
      interactions as well as formation of microcrystalline aggregates depending upon
      the molar ratios of CTAB and RB within the complex LB films. Presence of two
      types of species in the complex LB films was confirmed by fluorescence
      spectroscopy.

PMID- 17451730
TI  - Heterogeneous photodegradation of bisphenol A with iron oxides and oxalate in
      aqueous solution.
AB  - To understand the degradation of endocrine disrupting chemicals (EDCs) with
      existence of iron oxides and polycarboxylic acids in the natural environment, the
      photodegradation of bisphenol A (BPA) at the interface of iron oxides under UV
      illumination was conducted. Four iron oxides were prepared by a hydrothermal
      process and then sintered at different temperatures of 65, 280, 310, and 420
      degrees C named "IO-65," "IO-280," "IO-310," and "IO-420," respectively. The
      prepared iron oxides were characterized by X-ray diffraction (XRD) and Brunauer
      Emmett-Teller (BET) methods. The XRD pattern of IO-65 showed a crystal structure
      of lepidocrocite (gamma-FeOOH) and that of IO-420 demonstrated a crystal
      structure of hematite (alpha-Fe(2)O(3)), while IO-280 and IO-310 have the mixed
      crystal structures of maghemite (gamma-Fe(2)O(3)) and hematite. The BET results
      revealed that the specific surface areas decreased with the increase of sintering
      temperature. The results demonstrated that the photodegradation of BPA depends
      strongly on the properties of iron oxides and oxalate, and pH. The properties of
      iron oxides influenced strongly the dependence of the BPA degradation on the
      oxalate concentration. The optimal initial concentrations of oxalate for BPA
      degradation under UV illumination were determined to be 2.0, 2.0, 2.4, and 2.0 mM
      for IO-65, IO-280, IO-310, and IO-420, respectively. The first-order kinetic
      constants k for BPA degradation under UV illumination in the presence of oxalate
      with the optimal initial concentration are ranked as IO-280>IO-310>IO-65>IO-420.
      The experiments demonstrated that the optimal pH value should be in the range of
      3-4. Furthermore, the dependence of BPA degradation should be also attributable
      to the formation of the dissolved Fe-oxalate in the solution and the adsorbed Fe
      oxalate on the surface of iron oxides, and also the formation of hydrogen
      peroxide.

PMID- 17451731
TI  - Saving time when measuring BET isotherms.
AB  - The measurement of adsorption isotherms and the determination of surface
      properties of a solid by means of the BET equation usually takes a lot of time as
      it involves measurement of several dynamic adsorption curves each at a given gas
      pressure. Two different timesaving approaches are suggested: (a) the beginning of
      a single dynamic curve is considered and (b) the beginnings of a number of
      different dynamic curves is considered. Approach (a) is less time consuming than
      approach (b), where approach (b) yields more accurate estimates of the BET
      parameters. A discussion is given of the possibilities of using the time saving
      procedure of Jantti for the two approaches.

PMID- 17451732
TI  - Synthesis and amphiphilic properties of decanoyl esters of tri- and tetraethylene
      glycol.
AB  - Well-defined decanoyl triethylene glycol ester and decanoyl tetraethylene glycol
      ester were synthesized and compared to their ether counterparts (C(10)E(4) and
      C(10)E(3)). Their physicochemical properties i.e. critical micelle concentrations
      (CMC), cloud points, and equilibrium surface tensions were determined. Binary
      water-surfactant phase behavior was also studied by polarized optical microscopy.
      The stability of the ester bond was determined by investigating alkaline
      hydrolysis of the compounds. It was found that CMC, cloud point and equilibrium
      surface tension are roughly the same for corresponding ethers and esters. In the
      binary diagram, the esters form only lamellar phases, the area of which is
      smaller than that of the ether counterparts. These different behaviors can be
      related to the modification of the molecular conformation induced by the
      replacement of the ether group by the ester group.

PMID- 17451733
TI  - Copper- and ligand-free Sonogashira reaction catalyzed by palladium in
      microemulsion: effects of surfactant and alcohol.
AB  - A rapid copper- and ligand-free Sonogashira reaction was performed in an oil-in
      water microemulsion. Palladium nanoparticles can be in situ formed in the
      microemulsion without other reductants. The microemulsion containing in situ
      formed nano-Pd is an efficient system for the Sonogashira reaction. The reactions
      were faster in the microemulsion than in micelles. The effects of surfactant,
      alcohol, and temperature are discussed. Excellent yield of the Sonogashira
      reaction catalyzed by 0.5 mol% palladium could be achieved at 80 degrees C within
      2 min.

PMID- 17451734
TI  - Adsorption of phosphate and nitrate anions on ammonium-functionalized MCM-48:
      effects of experimental conditions.
AB  - In this study, ammonium-functionalized MCM-48 (Mobil Composite Material No. 48)
      was used as an adsorbent to remove nitrate (NO(-)(3)) and monobasic phosphate
      (H(2)PO(-)(4)) anions from aqueous solutions. The effects of operating conditions
      such as temperature, adsorbent loading, initial anion concentration, pH, and the
      presence of competitive ions on the adsorption performances were examined.
      Results showed that adsorption capacity decreased with increasing temperature.
      The adsorption capacity increased with adsorbent loading and initial anion
      concentration. The removal of nitrate was maximum at pH<8, while phosphate
      removal was maximized at pH 5. The adsorption was almost unaffected by the
      presence of competitive ions in the case of phosphate anions. However, their
      presence adversely affected nitrate adsorption. Desorption of both anions was
      rapidly achieved within 10 min using NaOH at 0.01 M. Regeneration tests showed
      that the adsorbent retained its capacity after 5 adsorption-desorption cycles.

PMID- 17451735
TI  - Effect of propyl paraben on the dipalmitoyl phosphatidic acid vesicles.
AB  - The effect of the preservative propyl paraben (PPB) on the phase transition and
      dynamics of dipalmitoyl phosphatidic acid (DPPA)-buffer (pH 7.4/9.3) vesicles has
      been studied using DSC and ((1)H and (31)P) NMR. These investigations were
      carried out with DPPA dispersion in both multilamellar vesicular (MLV) and
      unilamellar vesicular (ULV) forms. DSC results indicate that the mechanism by
      which PPB interact with the DPPA vesicles is similar in MLV and ULV and is
      independent of pH of the buffer used to form the dispersion. However, for a given
      concentration of PPB, the perturbation in DPPA bilayer is more when the
      dispersion is prepared in buffer pH 7.4. PPB affected both the thermotropic phase
      transition and the molecular mobility of the DPPA membrane. In the presence of
      PPB, the gel to liquid crystalline phase transition temperature (T(m)) of the
      DPPA vesicles decreases hence increases membrane fluidity due to reduced
      headgroup-headgroup interaction. For all concentrations, the PPB molecules seem
      to get intercalated between the polar groups of the phospholipids with its alkyl
      chain penetrating into the co-operative region. At high PPB concentration,
      additional transitions are observed whose intensity increases with increasing PPB
      concentration. The large enthalpy values obtained at high PPB concentration
      suggest that presence of PPB makes the DPPA bilayer more ordered (rigid). The
      interesting finding obtained with MLV is that the stable gel phase of DPPA-buffer
      (pH 9.3/7.4) system in the presence of high PPB concentration becomes a
      metastable gel phase, this metastable gel phase on equilibration at 25 degrees C
      or when cooled to -20 degrees C transforms to a stable crystalline phase(s). The
      intensity of this new phase(s) increases with increasing PPB concentration.
      However, the transition temperatures of these new phases are not significantly
      changed with increasing PPB concentration. The effect of inclusion of cholesterol
      in the PPB-free and PPB-doped DPPA dispersion was also studied.

PMID- 17451736
TI  - Solid acid catalysts from clays: preparation of mesoporous catalysts by chemical
      activation of metakaolin under acid conditions.
AB  - Natural kaolin was treated at 850 or 950 degrees C in air flow to give
      respectively the metakaolin samples MK8 and MK9. The obtained materials were
      successively treated at 90 degrees C with a 1 M solution of H(2)SO(4), for
      various time lengths. The acid treatment of MK8 was found to give a high surface
      area microporous material with good catalytic properties related to the high
      density of acid sites, while MK9 gave an ordered mesoporous material with a low
      density of acid sites. The materials were characterized by several techniques, X
      ray powder diffraction, thermogravimetric analysis, N(2) physisorption, scanning
      electron microscopy, and temperature-programmed desorption of ammonia. The 1
      butene isomerization was used as test reaction to evaluate the acidity of the
      samples.

PMID- 17451737
TI  - Silver microflowers and large spherical particles: Controlled preparation and
      their wetting properties.
AB  - In this article, we report a simple wet-chemical method to prepare silver
      microflowers and large spherical particles. The formation of the two different
      microstructures of silver is based on the reduction of AgNO(3) by para
      phenylenediamine in aqueous medium at room temperature. The controlling of the
      silver microstructures can be achieved only by adjusting the concentration of the
      reactants. It is found that the two different silver microstructures display
      opposite wetting properties. Large spherical silver particles exhibit
      superhydrophilic properties with a contact angle (CA) of close to 0 degrees,
      microflower-like silver particles exhibit highly hydrophobic properties with CA
      about 132 degrees. X-ray diffraction (XRD), X-ray photoelectron spectra (XPS) and
      UV-vis spectra are used to characterize the chemical structure of the obtained
      products.

PMID- 17451738
TI  - Flow cytometric assessment of estrogen receptor beta expression in bovine blood
      neutrophils.
AB  - The optimisation of a flow cytometric protocol for the determination of the
      estrogen receptor beta (ERbeta) expression in bovine blood neutrophils is
      described. The following final incubation conditions were obtained: fixation with
      0.25% formaldehyde and 70% methanol, both for 1 h; permeabilisation with 0.05%
      Triton X-100, overnight labelling at 4 degrees C with the primary antibody
      diluted at 10 microg/ml and subsequent labelling for 30 min on ice with the
      fluorescein isothiocyanate-conjugated secondary antibody at 8 microg/ml. Of the
      three anti-human or anti-rat ERbeta primary antibodies evaluated, only PA1-311
      was found to cross-react with bovine cells. Immunoblot analysis supports the
      obtained results. The flow cytometric technique allows reproducible quantitative
      determination of the ERbeta protein in neutrophils and may be a valuable tool for
      future expression studies in these cells of the innate immune system.

PMID- 17451740
TI  - In vitro and in vivo stimulation of extracellular signal-regulated kinase (ERK)
      by the prothoracicotropic hormone in prothoracic gland cells and its
      developmental regulation in the silkworm, Bombyx mori.
AB  - In this study, we investigated activation of the extracellular signal-regulated
      kinase (ERK) by the prothoracicotropic hormone (PTTH) in prothoracic gland cells
      of the silkworm, Bombyx mori. The results showed that the PTTH stimulated ERK
      phosphorylation as this depends on time and dose and ecdysteroidogenic activity.
      The ERK phosphorylation inhibitors, PD 98059 and U0126, blocked both basal and
      PTTH-stimulated ERK phosphorylation and ecdysteroidogenesis. In addition,
      activation of glandular ERK phosphorylation by the PTTH appeared to be
      developmentally regulated with the refractoriness of gland cells to the PTTH
      occurring during the latter stages of both the fourth and last larval instars.
      Moreover, in vitro activation of ERK phosphorylation of prothoracic glands by the
      PTTH was also verified by in vivo experiments: injection of the PTTH into day 6
      last instar larvae greatly increased the activity of glandular ERK
      phosphorylation and ecdysteroidogenesis. These results suggest that development
      specific changes in ERK phosphorylation may play a role in PTTH stimulation of
      ecdysteroidogenesis.

PMID- 17451739
TI  - Optimization and validation of an 8-color intracellular cytokine staining (ICS)
      assay to quantify antigen-specific T cells induced by vaccination.
AB  - Candidate HIV-1 vaccines currently being evaluated in clinical trials are
      designed to elicit HIV-1-specific cellular immunity. Intracellular cytokine
      staining (ICS) assays allow sensitive, quantitative ex vivo assessments of
      antigen-specific T cells including immunophenotyping of responding cells and
      measurement of multiple effector functions. Additionally, the use of banked
      cryopreserved PBMC samples makes this assay attractive in the setting of large
      efficacy trials where it is less feasible to perform immunoassays on freshly
      isolated samples. Here we describe extensive studies to optimize and
      quantitatively validate the 8-color ICS assay for use in clinical trials of
      candidate vaccines, which includes measurement of viable IFN-gamma, IL-2, TNF
      alpha and IL-4 producing CD4+ and CD8+ T cells. We show that omission of
      viability dye staining results in an over-estimate of the true antigen-specific T
      cell response by up to two-fold. After optimization, the 8-color assay was
      validated for specificity, precision, linearity, limit of quantitation and
      robustness. The assay has a lower quantitation limit generally below 0.04%,
      depending on the cytokine subset. Additionally, with appropriate gating, the 8
      color assay gives comparable cytokine-positive responses to those observed with
      the conventional 4-color assay. In conclusion, we provide the first description
      of a quantitatively validated ICS assay, which permits quantitative and
      qualitative evaluation of vaccine-induced immunogenicity and analysis of immune
      correlates of protection.

PMID- 17451741
TI  - Neuro-endocrine correlates of ovarian development and egg-laying behaviors in the
      primitively eusocial wasp (Polistes chinensis).
AB  - To explore the roles of biogenic amines in reproduction in workers in primitively
      eusocial societies, correlations between brain levels of biogenic amines and
      ovarian development or oviposition in workers of the paper wasp Polistes
      chinensis were investigated. Several workers in queenright colonies developed
      ovaries and were potential egg-layers. Maximum ovarian width was significantly
      correlated with brain levels of dopamine, serotonin and their metabolites (N
      acetyldopamine and N-acetylserotonin). Individuals with developed ovaries
      proceeded with yolk formation had significantly higher levels of brain dopamine,
      serotonin and N-acetyldopamine compared with individuals with undeveloped
      ovaries. Brain dopamine levels were higher in egg-laying individuals than in
      other individuals with developed ovaries. Thus, the workers of the paper wasp
      showed quantitative differences in brain dopamine levels correlated with
      reproduction. These results suggest that the brain levels of biogenic amines in
      paper wasp workers correspond to their tasks, and that there is a mechanism for
      promoting reproduction by dopamine, as previously reported in the workers of
      eusocial bees.

PMID- 17451742
TI  - The expression of a sexually selected trait correlates with different immune
      defense components and survival in males of the American rubyspot.
AB  - Recent studies have suggested that courtship trait expression indicates immune
      strength. However, most studies have measured only one immune parameter, have not
      assessed individual differences in immune ability according to time and have not
      controlled for ecological differences among individuals after an immune
      challenge. In this work, we tested this hypothesis and controlled for these
      factors using males of the American rubyspot damselfly which bear a wing red spot
      whose size is evolutionarily maintained via male-male territorial competition.
      Our general hypothesis was that territorial, large-spotted males, had a better
      immune ability compared to nonterritorial, small-spotted males. We expected that
      the following variables were greater in territorial males compared to
      nonterritorial males: spot size, phenoloxidase (PO) and hydrolytic enzymatic (HE)
      activity in males challenged and nonchallenged with a nylon implant, PO and HE
      activity rate; PO activity after a Serratia marcescens challenge, and survival
      after a nylon challenge controlling for activity and feeding differences. We
      found that territorial males showed larger spot areas, greater PO and HE activity
      (independently of whether they were challenged or not), a higher rate of PO and
      HE activity (but only expressed at 8h), greater PO production after the bacterial
      challenge, and a higher survival after the challenge. These results corroborate
      that males with more pronounced sexual traits have a superior immune function.

PMID- 17451743
TI  - vGNM: a better model for understanding the dynamics of proteins in crystals.
AB  - The dynamics of proteins are important for understanding their functions. In
      recent years, the simple coarse-grained Gaussian Network Model (GNM) has been
      fairly successful in interpreting crystallographic B-factors. However, the model
      clearly ignores the contribution of the rigid body motions and the effect of
      crystal packing. The model cannot explain the fact that the same protein may have
      significantly different B-factors under different crystal packing conditions. In
      this work, we propose a new GNM, called vGNM, which takes into account both the
      contribution of the rigid body motions and the effect of crystal packing, by
      allowing the amplitude of the internal modes to be variables. It hypothesizes
      that the effect of crystal packing should cause some modes to be amplified and
      others to become less important. In doing so, vGNM is able to resolve the
      apparent discrepancy in experimental B-factors among structures of the same
      protein but with different crystal packing conditions, which GNM cannot explain.
      With a small number of parameters, vGNM is able to reproduce experimental B
      factors for a large set of proteins with significantly better correlations
      (having a mean value of 0.81 as compared to 0.59 by GNM). The results of applying
      vGNM also show that the rigid body motions account for nearly 60% of the total
      fluctuations, in good agreement with previous findings.

PMID- 17451744
TI  - HotPatch: a statistical approach to finding biologically relevant features on
      protein surfaces.
AB  - We describe a fully automated algorithm for finding functional sites on protein
      structures. Our method finds surface patches of unusual physicochemical
      properties on protein structures, and estimates the patches' probability of
      overlapping functional sites. Other methods for predicting the locations of
      specific types of functional sites exist, but in previous analyses, it has been
      difficult to compare methods when they are applied to different types of sites.
      Thus, we introduce a new statistical framework that enables rigorous comparisons
      of the usefulness of different physicochemical properties for predicting
      virtually any kind of functional site. The program's statistical models were
      trained for 11 individual properties (electrostatics, concavity, hydrophobicity,
      etc.) and for 15 neural network combination properties, all optimized and tested
      on 15 diverse protein functions. To simulate what to expect if the program were
      run on proteins of unknown function, as might arise from structural genomics, we
      tested it on 618 proteins of diverse mixed functions. In the higher-scoring top
      half of all predictions, a functional residue could typically be found within the
      first 1.7 residues chosen at random. The program may or may not use partial
      information about the protein's function type as an input, depending on which
      statistical model the user chooses to employ. If function type is used as an
      additional constraint, prediction accuracy usually increases, and is particularly
      good for enzymes, DNA-interacting sites, and oligomeric interfaces. The program
      can be accessed online (at http://hotpatch.mbi.ucla.edu).

PMID- 17451745
TI  - Crystal structure and allosteric regulation of the cytoplasmic Escherichia coli L
      asparaginase I.
AB  - AnsA is the cytoplasmic asparaginase from Escherichia coli involved in
      intracellular asparagine utilization. Analytical ultracentifugation and X-ray
      crystallography reveal that AnsA forms a tetrameric structure as a dimer of two
      intimate dimers. Kinetic analysis of the enzyme reveals that AnsA is positively
      cooperative, displaying a sigmoidal substrate dependence curve with an [S](0.5)
      of 1 mM L-asparagine and a Hill coefficient (n(H)) of 2.6. Binding of L
      asparagine to an allosteric site was observed in the crystal structure
      concomitant with a reorganization of the quarternary structure, relative to the
      apo enzyme. The carboxyl group of the bound asparagine makes salt bridges and
      hydrogen bonds to Arg240, while the N(delta2) nitrogen interacts with Thr162.
      Mutation of Arg240 to Ala increases the [S](0.5) value to 5.9 mM, presumably by
      reducing the affinity of the site for L-asparagine, although the enzyme retains
      cooperativity. Mutation of Thr162 to Ala results in an active enzyme with no
      cooperativity. Transmission of the signal from the allosteric site to the active
      site appears to involve subtle interactions at the dimer-dimer interface and
      relocation of Gln118 into the vicinity of the active site to position the
      probable catalytic water molecule. These data define the structural basis for the
      cooperative regulation of the intracellular asparaginase that is required for
      proper functioning within the cell.

PMID- 17451746
TI  - Annexin A5 interacts with polycystin-1 and interferes with the polycystin-1
      stimulated recruitment of E-cadherin into adherens junctions.
AB  - Polycystin-1 is the gene product of PKD1, the first gene identified to be
      causative for the condition of autosomal dominant polycystic kidney disease
      (ADPKD). Mutations in PKD1 are responsible for the majority of ADPKD cases
      worldwide. Polycystin-1 is a protein of the transient receptor potential channels
      superfamily, with 11 transmembrane spans and an extracellular N-terminal region
      of approximately 3109 amino acid residues, harboring multiple putative ligand
      binding domains. We demonstrate here that annexin A5 (ANXA5), a Ca(2+) and
      phospholipid binding protein, interacts with the N-terminal leucine-rich repeats
      of polycystin-1, in vitro and in a cell culture model. This interaction is direct
      and specific and involves a conserved sequence of the ANXA5 N-terminal domain.
      Using Madin-Darby canine kidney cells expressing polycystin-1 in an inducible
      manner we also show that polycystin-1 colocalizes with E-cadherin at cell-cell
      contacts and accelerates the recruitment of intracellular E-cadherin to reforming
      junctions. This polycystin-1 stimulated recruitment is significantly delayed by
      extracellular annexin A5.

PMID- 17451747
TI  - Specific recognition of saturated and 4,5-unsaturated hexuronate sugars by a
      periplasmic binding protein involved in pectin catabolism.
AB  - The process of pectin depolymerization by pectate lyases and glycoside hydrolases
      produced by pectinolytic organisms, particularly the phytopathogens from the
      genus Erwinia, is reasonably well understood. Indeed each extracellular and
      intracellular catabolic stage has been identified using either genetic,
      bioinformatic or biochemical approaches. Nevertheless, the molecular details of
      many of these stages remain unknown. In particular, the mechanism and ligand
      binding profiles for the transport of pectin degradation products between
      cellular compartments remain entirely uninvestigated. Here we present the
      structure of TogB, a 45.7 kDa periplasmic binding protein from Yersinia
      enterocolitica. This protein is a component of the TogMNAB ABC transporter
      involved in the periplasmic transport of oligogalacturonides. In addition to the
      unliganded complex (at 2.2 A), we have also determined the structures of TogB in
      complex with digalacturonic acid (at 2.2 A), trigalacturonic acid (at 1.8 A) and
      4,5-unsaturated digalacutronic acid (at 2.3 A). The molecular determinants of
      oligogalacturonide binding include a novel salt-bridge between the non-reducing
      sugar uronate group, selectivity for the unsaturated ligand, and the overall
      sugar configuration. Complementing this are UV difference and isothermal
      titration calorimetry experiments that highlight the thermodynamic basis of
      ligand specificity. The ligand binding profiles of the TogMNAB transporter
      complex nicely complement pectate lyase-mediated pectin degradation, which is a
      significant component of pectin depolymerization reactions.

PMID- 17451748
TI  - Functional and morphological effects of repeated sodium arsenite exposure on rat
      peripheral sensory nerves.
AB  - Exposure to inorganic arsenic (iAs) is known to result in peripheral neuropathy.
      To better understand the functional and morphological consequences of iAs
      exposure, we examined the electrophysiological and histological characteristics
      of the sensory sural nerves in adult Male Wistar rats following 30 days of sodium
      arsenite administration by gavage (10 mg/kg body weight/day). Arsenic (As) levels
      in the peripheral nerves of exposed animals were about 150 times greater than
      those in controls. Lipid peroxidation was also increased in iAs-exposed animals.
      Compound action potentials (CAPs) evoked in iAs-exposed nerves were characterized
      by a slower conduction velocity ( approximately 26%). iAs-exposed nerves also
      showed a trend towards a decreased CAP area ( approximately 35%). These
      electrophysiological changes were consistent with histological alterations such
      as a approximately 56% decrease in myelin thickness. In addition, the perimeter
      and transverse area of axons were reduced to 29% and 45% of control,
      respectively. Our results suggest that accumulation of As produced by iAs
      exposure induces oxidative damage, severe demyelination, and other morphological
      alterations in axons of peripheral nerves. These changes may, in turn, induce
      changes in the generation and propagation of action potentials in peripheral
      nerves, leading to decreased transmission of information from peripheral sensory
      organs to the central nervous system.

PMID- 17451749
TI  - Exploring the role of cation-pi interactions in glycoproteins lipid-binding
      proteins and RNA-binding proteins.
AB  - We have analyzed and compared the influence of cation-pi interactions in
      glycoproteins (GPs), lipid-binding proteins (LBPs) and RNA-binding proteins
      (RBPs) in this study. We observed that all the proteins included in the study had
      profound cation-pi interactions. There is an average of one energetically
      significant cation-pi interaction for every 71 residues in GPs, for every 58
      residues in LBPs and for every 64 residues in RBPs. Long-range contacts are
      predominant in all the three types of proteins studied. The pair-wise cation-pi
      interaction energy between the positively charged and aromatic residues shows
      that Arg-Trp pair energy was the strongest among all six possible pairs in all
      the three types of proteins studied. There were considerable differences in the
      preference of cation-pi interacting residues to different secondary structure
      elements and ASA and these might contribute to differences in biochemical
      functions of GPs, LBPs and RBPs. It was interesting to note that all the five
      residues involved in cation-pi interactions were found to have stabilization
      centers in GPs, LBPs and RBPs. Majority of the cation-pi interacting residues
      investigated in the present study had a conservation score of 6, the cutoff value
      used to identify the stabilizing residues. A small percentage of cation-pi
      interacting residues were also present as stabilizing residues. The cation-pi
      interaction-forming residues play an important role in the structural stability
      of in GPs, LBPs and RBPs. The results obtained in this study will be helpful in
      further understanding the stability, specificity and differences in the
      biochemical functions of GPs, LBPs and RBPs.

PMID- 17451750
TI  - Modeling hepatitis C virus dynamics: liver regeneration and critical drug
      efficacy.
AB  - Mathematical models for hepatitis C viral (HCV) RNA kinetics have provided a
      means of evaluating the antiviral effectiveness of therapy, of estimating
      parameters such as the rate of HCV RNA clearance, and they have suggested
      mechanism of action against HCV for both interferon and ribavirin. Nevertheless,
      the model that was originally formulated by Neumann et al. [1998. Hepatitis C
      viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy.
      Science 282 (5386), 103-107] is unable to explain all of the observed HCV RNA
      profiles under treatment e.g., a triphasic viral decay and a viral rebound to
      baseline values after the cessation of therapy. Further, the half-life of
      productively HCV-infected cells, estimated from the second phase HCV RNA decline
      slope, is very variable and sometimes zero with no clear understanding of why. We
      show that extending the original model by including hepatocyte proliferation
      yields a more realistic model without any of these deficiencies. Further, we
      define and characterize a critical drug efficacy, such that for efficacies above
      the critical value HCV is ultimately cleared, while for efficacies below it, a
      new chronically infected viral steady-state level is reached.

PMID- 17451751
TI  - Medium-term responses of rocky bottoms to sewage discharges from a deepwater
      outfall in the NE Atlantic.
AB  - An investigation on the effects of deepwater outfall discharges on the status of
      rocky reef communities was carried out. The sanitation system was found to be an
      environmentally suitable option for the protection of those habitats situated in
      high energy coastal environments. Sediments occurring between the predominating
      rocky substrates showed low values of the fine fraction (<63microm) and organic
      matter content. In addition, high average concentrations of Cd, Hg and Zn were
      found in these sediments, though these values were similar to those registered in
      non-affected sites, far away from the outfall. On the other hand, those
      assemblages typical of hard substrates that settled near the outfall showed an
      increase in total richness and abundance of macroinvertebrates. Moreover, the
      average number of species of each taxonomic group, a good indicator of the
      maintenance of the previous trophic structure, only varied considerably over time
      at the rip-rap protection. In a global context, those changes were not directly
      related to the discharge disturbances, but to the natural variability or the
      successional processes occurring within those communities. Only communities
      dwelling in the rip-rap protection area were affected by the proximity of the
      discharges.

PMID- 17451752
TI  - Inducible NO synthase (iNOS) in human neutrophils but not pulmonary microvascular
      endothelial cells (PMVEC) mediates septic protein leak in vitro.
AB  - Sepsis-induced acute lung injury (ALI) is characterized by injury of the
      pulmonary microvascular endothelial cells (PMVEC) leading to high-protein
      pulmonary edema. Inducible NO synthase (iNOS) mediates trans-PMVEC protein leak
      in septic mice in vivo and in murine PMVEC under septic conditions in vitro, but
      the role of iNOS in human PMVEC protein leak has not been addressed. We
      hypothesized that iNOS in human neutrophils, but not human PMVEC, mediates septic
      trans-PMVEC protein leak in vitro. We isolated human PMVEC from lung tissue using
      magnetic bead-bound anti-PECAM antibody and assessed Evans blue albumin leak
      across human PMVEC monolayers under septic conditions in the presence/absence of
      human neutrophils. PMVEC were used at passages 3-4, seeded on 3 mum Transwell
      inserts and grown to confluence. Cytomix-stimulated trans-PMVEC albumin leak was
      not attenuated by pre-treatment with 1400 W, a selective iNOS inhibitor, or l
      NAME, a non-selective NOS inhibitor. In neutrophil-PMVEC co-culture, basal
      unstimulated trans-EB-albumin leak was 0.6+/-0.3%, which was increased by cytomix
      stimulation to 11.5+/-4.4%, p<0.01. Cytomix-stimulated EB-albumin leak in
      neutrophil-PMVEC co-cultures was inhibited by pre-treatment with 1400 W (3.8+/
      1.0%, p<0.05) or l-NAME (4.0+/-1.1%, p<0.05). Pre-treatment of neutrophil-PMVEC
      co-cultures with PEG-SOD (superoxide scavenger) and FeTPPS (peroxynitrite
      scavenger) also significantly attenuated neutrophil-dependent cytomix-stimulated
      leak (4.7+/-3.0%, p<0.05; 0.5+/-1.0%, p<0.01, respectively). In conclusion, trans
      human PMVEC albumin leak under septic conditions is dependent on iNOS activity
      specifically in neutrophils, but not in PMVEC themselves. Septic neutrophil
      dependent trans-PMVEC albumin leak may be mediated by peroxynitrite.

PMID- 17451753
TI  - Hyperoxia decreases cutaneous blood flow in high-perfusion areas.
AB  - The mechanism by which hyperoxia decreases blood flow is still not understood.
      Hyperoxemia-induced vasoconstriction is known to occur in many organs, including
      brain and retina, skeletal muscle, and myocardium. Whether this also occurs in
      skin is unknown. This study was conducted in healthy volunteers exposed
      intermittently to 100% oxygen (F(I)O(2) 1.0). Perfusion of forearm skin was
      measured by laser Doppler imaging (LDI). In series 1, it was measured in 7
      subjects before, during, and after 15 min of oxygen breathing. In series 2, flow
      was measured, also during air and O(2) breathing, after perfusion was raised by
      (a) sympathetic blockade (induced by a topically applied local anesthetic) (n=9)
      and by (b) current-induced vasodilation (n=8). In normal unperturbed skin, there
      was no significant change with hyperoxia. When basal perfusion was raised by
      topical anesthesia or by current, there was also no change in mean perfusion
      overall with hyperoxia. However, areas with the highest perfusion (upper decile)
      showed a significant perfusion decrement with hyperoxia (-30% and -20%,
      respectively; p<0.001). Vasoconstriction with hyperoxia has been demonstrated in
      human skin. The fact that it is observed only when flow is increased above basal
      levels and then only in high-flow vessels suggests that cutaneous blood flow
      control is primarily regulated by variables other than oxygen.

PMID- 17451754
TI  - Blockade of GABA(A) receptors within the extended amygdala attenuates D(2)
      regulation of alcohol-motivated behaviors in the ventral tegmental area of
      alcohol-preferring (P) rats.
AB  - The dopamine (DA) mesolimbic pathway, which originates from DA cell bodies within
      the ventral tegmental area (VTA), has been shown by various studies to play a
      role in the mediation of various drugs of abuse including alcohol (EtOH). It has
      been suggested that the VTA's control of EtOH reward is mediated in part by the
      D2 receptors within the VTA. These receptors may be under the regulation of
      reciprocal GABAergic inputs from forebrain components of the mesolimbic path such
      as the nucleus accumbens (NAcc), a classic EtOH reward substrate, and the bed
      nucleus of the stria terminalis, a substrate recently implicated in EtOH
      reinforcement, forming a self-regulating feedback loop. To test this hypothesis,
      D2 regulation of EtOH self-administration (SA) was evaluated by the microinfusion
      of the D2 antagonist eticlopride into the VTA of P rats, which produced profound
      reductions in EtOH SA in the highest (20.0 and 40.0microg) doses tested in both
      BST/VTA and NAcc/VTA implanted P rats. To determine the role of GABA in the
      mediation of EtOH SA, a 32.0ng dose the non-selective GABA antagonist SR 95531
      was microinfused into the BST producing no effect on responding for EtOH and into
      the NAcc which lead to a reduction in EtOH responding. Finally, the hypothesis
      that GABA innervation of the VTA from the mesolimbic forebrain may influence EtOH
      SA was examined by the simultaneous infusion of eticlopride (40.0microg) into the
      VTA and SR 95531 (32.0ng) into either the BST or NAcc. This combination infusion
      completely attenuated the reduction in EtOH SA observed with the 40.0microg dose
      of eticlopride alone in both groups of animals. These results suggest that while
      the D2 receptors within the VTA regulate EtOH-motivated behaviors, this is
      modulated by GABAergic input from the mesolimbic forebrain, specifically from the
      BST and NAcc.

PMID- 17451755
TI  - The GABAB receptor agonist baclofen prevents heroin-induced reinstatement of
      heroin-seeking behavior in rats.
AB  - Opiate addiction is a chronic relapsing disorder characterized by high rates of
      relapse. The gamma-aminobutyric acid GABA(B) receptor agonist baclofen is known
      to affect the reinforcing effects of several drugs of abuse, including heroin, as
      well as to decrease cue-maintained responding for heroin, cocaine and nicotine
      and suppress alcohol deprivation effect in rats. Here we studied the effect of
      baclofen on the reinstatement of extinguished heroin-seeking behavior triggered
      by a priming injection of heroin in abstinent rats trained to stably self
      administer heroin (30 microg/kg per infusion) under a continuous reinforcement
      schedule. Following extinction, the effect of non-contingent non-reinforced
      primings with heroin, baclofen or heroin/baclofen combination on the resumption
      of responding was evaluated. Results indicate that heroin priming (0.25mg/kg)
      promptly reinitiated heroin-seeking behavior, an effect dose-dependently reduced
      by baclofen at doses (0.625 and 1.25mg/kg) not affecting responding per se.
      Importantly, baclofen did not affect locomotion either alone or in combination
      with heroin, dispelling any doubt as to the eliciting of possible non-specific
      (motor) effects. The present results show that GABA(B) receptor activation may
      reduce the propensity to resume drug-induced heroin-seeking behavior thus
      offering a possible approach in maintaining opiate abstinence.

PMID- 17451756
TI  - Error analyses reveal contrasting deficits in "theory of mind":
      neuropsychological evidence from a 3-option false belief task.
AB  - Perspective taking is a crucial ability that guides our social interactions. In
      this study, we show how the specific patterns of errors of brain-damaged patients
      in perspective taking tasks can help us further understand the factors
      contributing to perspective taking abilities. Previous work [e.g., Samson, D.,
      Apperly, I. A., Chiavarino, C., & Humphreys, G. W. (2004). Left temporoparietal
      junction is necessary for representing someone else's belief. Nature
      Neuroscience, 7, 499-500; Samson, D., Apperly, I. A., Kathirgamanathan, U., &
      Humphreys, G. W. (2005). Seeing it my way: A case of a selective deficit in
      inhibiting self-perspective. Brain, 128, 1102-1111] distinguished two components
      of perspective taking: the ability to inhibit our own perspective and the ability
      to infer someone else's perspective. We assessed these components using a new
      nonverbal false belief task which provided different response options to detect
      three types of response strategies that participants might be using: a complete
      and spared belief reasoning strategy, a reality-based response selection strategy
      in which participants respond from their own perspective, and a simplified
      mentalising strategy in which participants avoid responding from their own
      perspective but rely on inaccurate cues to infer the other person's belief. One
      patient, with a self-perspective inhibition deficit, almost always used the
      reality-based response strategy; in contrast, the other patient, with a deficit
      in taking other perspectives, tended to use the simplified mentalising strategy
      without necessarily transposing her own perspective. We discuss the extent to
      which the pattern of performance of both patients could relate to their executive
      function deficit and how it can inform us on the cognitive and neural components
      involved in belief reasoning.

PMID- 17451757
TI  - Multivariate normative comparisons.
AB  - In neuropsychological evaluations and single case research generally a number of
      tests are administered, since the interest is not in a single, but in multiple
      characteristics of a patient. The typical problem is to decide whether or not a
      patient is different from normal controls with respect to one or more of these
      characteristics. Consideration of each characteristic separately entails an
      increased risk of a false positive decision (a wrongful decision that the patient
      is abnormal, or a type 1 error). From a statistical point of view this calls for
      a multivariate analysis. In this paper, we propose two approaches to perform
      normative comparisons for such multivariate data: Bonferroni corrected univariate
      comparisons and a multivariate comparison. Both approaches allow for the testing
      of unidirectional (two-sided) as well as directional (one-sided) hypothesis, i.e.
      the hypothesis that a patient deviates in a negative sense from the norm. Monte
      Carlo simulations were performed to check if the type I error of both approaches
      is adequately controlled, and to investigate the power of both approaches to
      detect deviation from the norm. The results indicate that the type I error rate
      of both approaches is correct, even in small samples. The results also indicate
      that the power is higher for the univariate approach if the normative sample size
      is very small (i.e. just exceeds the number of tests administered). In larger
      samples, the multivariate comparison has in general increased power. We
      illustrate both approaches with a clinical example of patients with Parkinson
      disease, who received deep brain stimulation to alleviate motor symptoms, and who
      were neuropsychologically evaluated to detect possible cognitive side effects.

PMID- 17451758
TI  - Association between auditory and visual symptoms of unilateral spatial neglect.
AB  - Unilateral spatial neglect due to right brain damage (RBD) can occur in several
      different sensory modalities in the same patient. Previous studies of the
      association between auditory and visual neglect have yielded conflicting
      outcomes. Most such studies have compared performance on relatively simple
      clinical measures of visual neglect, such as target cancellation, with that on
      more sophisticated measures of auditory perception. This is problematic because
      such tasks are typically not matched for the cognitive processes they exercise.
      We overcame this limitation by using equivalent visual and auditory versions of
      extinction and temporal-order judgment (TOJ) tasks. RBD patients demonstrated
      lateralized deficits on both visual and auditory tasks when compared with same
      aged, healthy controls. Critically, a significant association between the
      severity of visual and auditory deficits was apparent on the TOJ task but not the
      extinction task, suggesting that even when task demands are matched across
      modalities, dissociations between visual and auditory neglect can be apparent.
      Across the auditory tasks, patients showed more pronounced deficits for verbal
      stimuli than for non-verbal stimuli. These findings have implications for recent
      models proposed to explain the role of spatial attention in multimodal
      perception.

PMID- 17451759
TI  - Supramodal language comprehension: role of the left temporal lobe for listening
      and reading.
AB  - In this fMRI study, we aimed at identifying the cortical areas engaged in
      supramodal processing of language comprehension. BOLD changes were recorded in 19
      healthy right-handed subjects reading or listening to a story. During the visual
      control tasks the volunteers attended to a series of continuous letterstrings or
      a fixation cross, while during the acoustic control tasks either a reversed text
      or white noise were presented. The conjunction of the visual and acoustic story
      processing yielded left-dominant activations which in comparison to language-like
      stimuli focused to the left middle temporal gyrus as well as to the supramarginal
      gyrus. We conclude that the core structure representing supramodal language
      comprehension is the left temporal lobe at both banks of the superior temporal
      sulcus.

PMID- 17451760
TI  - Galactan sulfate of Grateloupia indica: Isolation, structural features and
      antiviral activity.
AB  - Natural compounds offer interesting pharmacological perspectives for antiviral
      drug development with regard to broad-spectrum antiviral properties and novel
      modes of action. In this study, we have analyzed polysaccharide fractions
      isolated from Grateloupia indica. The crude water extract (GiWE) as well as one
      fraction (F3) obtained by anion exchange chromatography had potent anti-HSV
      activity. Their inhibitory concentration 50% (IC50) values (0.12-1.06 microg/ml)
      were much lower than cytotoxic concentration 50% values (>850 microg/ml). These
      fractions, which were effective antiviral inhibitors if added only during the
      adsorption period, had very low anticoagulant activity. Furthermore, they had no
      direct inactivating effect on virions in a virucidal assay. Chemical,
      chromatographic and spectroscopic methods showed that the active polysaccharide,
      which has an apparent molecular mass of 60 kDa and negative specific rotation
      [alpha]D(32) -16 degrees (c 0.2, H2O), contains alpha-(1-->4)- and alpha-(1-->3)
      linked galactopyranose residues. Sulfate groups, if present, are located mostly
      at C-2/6 of (1-->4)- and C-4/6 of (1-->3)-linked galactopyranosyl units, and are
      essential for the anti herpetic activity of this polymer.

PMID- 17451761
TI  - A short history of the Multidisciplinary Public Health Forum.
AB  - The Multidisciplinary Public Health Forum (MPHF) was a 'network of networks' that
      was formed through grass roots public conferences held during the mid 1990s. It
      championed the development of a trained, developed and accredited
      multidisciplinary public health workforce in the UK. This paper draws on
      documentary evidence and from a series of semi-formal interviews held with
      individuals who were involved in the development and work of the Forum, to
      explore why the Forum was influential, the key milestones of the journey and the
      lessons that we might learn for the continued development of the public health
      function.

PMID- 17451762
TI  - Through the glass ceiling - and back again: the experiences of two of the first
      non-medical directors of public health in England.
AB  - In 2001, the English Department of Health announced a radical re-organisation of
      the NHS under the banner of 'shifting the balance of power'. As part of this re
      organisation health authorities were abolished and the main NHS public health
      responsibilities devolved to the new primary care trusts (PCTs) from April 2002.
      Following several years of campaigning by the Multidisciplinary Public Health
      Forum (MPHF), in November 2001 the Acting Minister for Public Health, Lord Hunt,
      announced that PCT director of public health (DPH) posts would be open to
      'suitably qualified' candidates from any discipline. From April 2002 a number of
      new DsPH from backgrounds other than medicine were appointed. This paper reports
      on the experiences of two such DsPH who shared a commitment to multidisciplinary
      public health, but who did not wholly share the objectives of the MPHF. We place
      the opening of PCT DPH posts in the context of tensions within NHS public health
      between a focus on health services versus the wider determinants of health, and
      the development of multidisciplinary public health. The paper reflects on both
      the degree of change this opening represented and the limitations and tensions
      such appointments exposed.

PMID- 17451763
TI  - Sharing the business of public health.

PMID- 17451764
TI  - Multidisciplinary public health: what sort of victory?
AB  - Multidisciplinary public health (MDPH) has been a phenomenon in the UK of the
      1990s and the early 21st century. Its achievement has been seen as a victory for
      non medical interests. While acknowledging this, the paper questions what sort of
      victory this represents. Public health in its sanitary phase in the mid-19th
      century was, after all, what passed for multidisciplinary with its mix of
      engineers, doctors and statisticians. Is the present simply a return to the
      sanitary phase? The paper argues that it is not, and that contemporary public
      health badly needs clearer definition. It identifies three dimensions of recent
      public health. Public health can be an occupation; a discourse or movement, and
      also an institutional location of which public health research is part. Looked at
      in this frame, public health has been multidisciplinary in the post war period.
      The development of public health research out of social medicine in the 1950s was
      multidisciplinary. Public health campaigning, separate from public health
      professionals, has also been multidisciplinary since the 1970s. Public health as
      an occupation has been preoccupied with its professional positioning. Will the
      wider multidisciplinary impetus of public health now be lost in a preoccupation
      with status?

PMID- 17451765
TI  - The normal electrocardiogram of four species of conscious raptors.
AB  - The aim of this study was to describe normal ECG patterns and values in four
      species of conscious raptors (Eurasian kestrel, Griffon vulture, Little owl, and
      Eurasian Eagle owl). Electrocardiograms were carried out in 75 conscious birds
      belonging to four species of raptors. Lead II waveforms were analysed to
      determine amplitudes and durations of waves and intervals. Morphologic patterns
      of P-QRS-T deflections were analysed in the six limb leads. Rhythm, heart rate,
      mean electrical axis, presence of Ta wave, ST slurring, and P-on-T phenomenon
      were also studied. The influence of species, body weight and heart rate in
      electrocardiographic variables were statistically analysed (P < 0.05). Sinus
      rhythm was present in all tracings, showing sinus arrhythmia in four cases. Ta
      wave was present in six tracings and P-on-T phenomenon in four. ST segment could
      be identified in all tracings, being mainly high above baseline. Significant
      differences between species were found for all the electrocardiographic
      parameters. The heart rate and body weight were also found to be a significant
      influence in most parameters. This study provides electrocardiographic data for
      four species of raptors that can be used to establish comparisons for clinical
      purposes.

PMID- 17451766
TI  - Cyanobacteria and their toxins in treated-water storage reservoirs in Abha city,
      Saudi Arabia.
AB  - Occurrence of toxic cyanobacteria in drinking and recreational waters poses human
      health at risk as they can release potent toxins into the water. In the present
      study, open and covered treated-water storage reservoirs as well as their
      relevant tap waters in Abha city, Saudi Arabia, were surveyed for the presence of
      cyanobacteria and their toxins. The results revealed the contamination of most
      open reservoir and tap waters by algae and cyanobacteria, with an abundance of
      toxigenic species of cyanobacteria. Depending on the results of the Limulus
      amebocyte lysate (LAL) assay and enzyme linked immunosorbent assay (ELISA),
      endotoxins and microcystins (MCYSTs) were found in most open reservoir and tap
      waters at concentrations up to 32 EU ml(-1) and 0.3 microg ml(-1), respectively.
      The extracts of axenic cultures of most cyanobacterial species isolated from
      these reservoirs showed activity to LAL assay, with large endotoxin amounts
      obtained in Calothrix parietina (490 EU g(-1)) and Phormidium tenue (210 EU g(
      1)). Based on ELISA and HPLC analysis for these extracts, only C. parietina can
      produce MCYSTs (202 microg g(-1)) with a profile consisting of MCYST-RR and -LR.
      This study suggests that open treated-water storage reservoirs should be covered
      to prevent the presence of cyanobacteria and their toxins in such drinking and
      recreational waters.

PMID- 17451767
TI  - Isolation and functional characterization of a new myotoxic acidic phospholipase
      A(2) from Bothrops pauloensis snake venom.
AB  - This article reports the purification procedure and the biochemical/functional
      characterization of Bp-PLA(2), a new myotoxic acidic phospholipase A(2) from
      Bothrops pauloensis snake venom. It was highly purified through three
      chromatographic steps (ion-exchange on CM-Sepharose, hydrophobic chromatography
      on Phenyl-Sepharose and RP-HPLC on a C8 column). Bp-PLA(2) is a single-chain
      protein of 15.8kDa and pI 4.3. Its N-terminal sequence revealed a high homology
      with other Asp49 acidic PLA(2)s from snake venoms. Its specific activity was
      585.3U/mg. It displayed a high indirect hemolytic activity and inhibited platelet
      aggregation induced by collagen or ADP. It also induced in vivo edema and
      myotoxicity. Pretreatment of Bp-PLA(2) with BPB reduced the enzymatic activity,
      the inhibitory action on platelet aggregation and myotoxicity in vitro.
      Morphological analyses indicated that Bp-PLA(2) induced an intense edema, with
      visible leukocyte infiltrate and damaged muscle cells 24h after injection. Acidic
      myotoxic PLA(2)s from Bothrops snake venoms are still not extensively explored
      and knowledge of their structural and functional features will contribute for a
      better understanding of their action mechanism regarding enzymatic and toxic
      activities.

PMID- 17451768
TI  - Involvement of carrier-mediated transport system in uptake of tetrodotoxin into
      liver tissue slices of puffer fish Takifugu rubripes.
AB  - Although puffer fish contain tetrodotoxin (TTX) at a high concentration mainly in
      liver, the underlying mechanism remains to be elucidated. In the present study,
      uptake of TTX into the liver tissue slices of puffer fish Takifugu rubripes was
      investigated by in vitro incubation experiment. When T. rubripes liver slices
      were incubated with 0-2000microM TTX at 20 degrees C for 60min, the uptake rates
      exhibited non-linearity, suggesting that the TTX uptake into T. rubripes liver is
      carrier-mediated. The TTX uptake was composed of a saturable component (V(max)
      47.7+/-5.9pmol/min/mg protein and K(m) 249+/-47microM) and a non-saturable
      component (P(dif) 0.0335+/-0.0041microL/min/mg protein). The uptake of TTX was
      significantly decreased to 0.4 and 0.6 fold by the incubation at 5 degrees C and
      the replacement of sodium-ion by choline in the buffer, respectively, while it
      was not affected by the presence of 1mM l-carnitine, p-aminohippurate,
      taurocholate or tetraethylammonium. The TTX uptake by black scraper Thamnaconus
      modestus liver slices was much lower than that of T. rubripes and independent of
      the incubation temperature, unlike T. rubripes. These results reveal the
      involvement of carrier-mediated transport system in the TTX uptake by puffer fish
      T. rubripes liver slices.

PMID- 17451770
TI  - Bax-dependent mitochondrial membrane permeabilization enhances IRF3-mediated
      innate immune response during VSV infection.
AB  - An effective type I interferon (IFN-alpha/beta) response is critical for the
      control of many viral infections. Using an oncolytic strain of vesicular
      stomatitis virus, we have examined the cross-talk between virus-induced apoptosis
      and initiation of innate immune response. The intrinsic apoptotic cascade,
      specifically the Bax-Bcl-2-Caspase-9 cascade, was revealed as the primary pathway
      of VSV-induced apoptosis. Cell death was significantly reduced in BaxBak(-/-)
      murine embryonic fibroblasts (MEFs) and in human A549 epithelial cells treated
      with siRNA against Bax. Although inhibition of apoptosis resulted in enhanced
      virus replication in the BaxBak(-/-) MEFs as compared to wild-type cells,
      induction of the IFN antiviral response and expression of cytokine genes were
      attenuated in virus-infected cells. Moreover, Bax but not Bak pro-apoptotic
      protein was required for IRF-3 phosphorylation and activation, further
      substantiating a role for the intrinsic mitochondrial pathway in the innate
      immune response. Therefore, virus-induced apoptosis through a Bax-dependent
      mitochondrial pathway appears to enhance the full development of the IRF-3
      mediated IFN antiviral response.

PMID- 17451769
TI  - Silencing and complementation of reovirus core protein mu2: functional
      correlations with mu2-microtubule association and differences between virus- and
      plasmid-derived mu2.
AB  - A low-copy component of mammalian reovirus particles is mu2, an 83-kDa protein
      encoded by the M1 viral genome segment and packaged within the viral core.
      Previous studies have identified mu2 as a nucleoside triphosphate
      phosphohydrolase (NTPase) as well as an RNA 5'-triphosphate phosphohydrolase
      (RTPase), putatively involved in reovirus RNA synthesis and/or 5'-capping. Other
      studies have identified mu2 as a microtubule-binding protein, which also
      associates with the viral factory matrix protein muNS and thereby anchors the
      factories to cellular microtubules during infections by most reovirus strains. To
      extend studies of mu2 functions during infection, we tested a small interfering
      RNA (siRNA) directed against the M1 plus-strand RNAs of reovirus strains Type 1
      Lang (T1L) and Type 3 Dearing (T3D). The siRNA strongly suppressed mu2 expression
      by either strain and reduced infectious yields in a strain-dependent manner. This
      first strain difference was genetically mapped to the M1 genome segment and
      tentatively assigned to a single mu2 sequence polymorphism, Pro/Ser208, which
      also determines a T1L-T3D strain difference in microtubule association. The siRNA
      based defect in mu2 expression was rescued by plasmids, containing silent
      mutations in the siRNA-targeted sequence, which encoded either T1L or T3D mu2,
      but the growth defect was rescued only by T1L mu2. This second strain difference
      was also mapped to Pro/Ser208, in that swapping this one residue between T1L and
      T3D mu2 reversed the rescue phenotypes. Thus, the T1L-T3D strain difference in
      mu2-microtubule association was correlated not only with the extent of reduction
      in infectious yields by the siRNA but also with the extent of rescue by plasmid
      derived mu2. In addition, the rescue capacity of T1L mu2 was abrogated by
      nocodazole treatment, providing independent evidence for the importance of mu2
      microtubule association in plasmid-based rescue. In two separate cases, the
      results revealed functional differences between virus- and plasmid-derived mu2.
      Ala substitutions within the NTP-binding motif of T1L mu2 also abrogated its
      rescue capacity, suggesting that the NTPase or RTPase activity of mu2 is
      additionally required for effective viral growth.

PMID- 17451771
TI  - High level of genetic heterogeneity in S and P genes of genotype D hepatitis B
      virus.
AB  - The genetic heterogeneity of hepatitis B virus (HBV) genotypes and subgenotypes
      was investigated by directly sequencing amplified PreS, S and P genes of HBV
      isolates obtained from the plasma of 99 subjects with chronic HBV infection.
      Genotype D showed the greatest intragenotypic and intrasubgenotypic divergence:
      in particular, the a determinant was mutated in 58.2% of the genotype D patients,
      two of whom showed prototypic vaccine-induced escape mutants at codon 145.
      Moreover, five sites under significant positive selection were found in the S
      protein of the D isolates: one in the a determinant and four in the highly
      hydrophobic C terminal. Our results suggest that careful surveillance of vaccine
      induced escape mutants should be considered in populations with highly frequent
      genotype D infections, and raise questions concerning the possible relationship
      between the genetic heterogeneity, host immunity and pathogenicity of this HBV
      genotype.

PMID- 17451772
TI  - Evolution of a novel 5-amino-acid insertion in the beta3-beta4 loop of HIV-1
      reverse transcriptase.
AB  - HIV-1 isolates harbouring an insertion in the beta3-beta4 loop of reverse
      transcriptase (RT) confer high-level resistance to nucleoside analogues. We have
      identified a novel 5-amino-acid insertion (KGSNR amino acids 66-70) in a patient
      on prolonged nucleoside combination therapy (didanosine and stavudine) and
      investigated which factors were responsible for its outgrowth. Remarkably, only
      small fold increases in drug resistance to nucleoside analogues were observed
      compared to wild type. The insertion variant displayed a reduced replicative
      capacity in the absence of inhibitor, but had a slight replicative advantage in
      the presence of zidovudine, didanosine or stavudine, resulting in the selection
      and persistence of this insertion in vivo. Mathematical analyses of longitudinal
      samples indicated a 2% in vivo fitness advantage for the insertion variant
      compared to the initial viral population. The novel RT insertion variant
      conferring low levels of resistance was able to evolve towards a high-level
      resistant replication-competent variant.

PMID- 17451773
TI  - Chronic wasting disease of deer and elk in transgenic mice: oral transmission and
      pathobiology.
AB  - To study the pathogenesis of chronic wasting disease (CWD) in deer and elk,
      transgenic (tg) mice were generated that expressed the prion protein (PrP) of
      deer containing a glycine at amino acid (aa) 96 and a serine at aa 225 under
      transcriptional control of the murine PrP promoter. This construct was introduced
      into murine PrP-deficient mice. As anticipated, neither non-tg mice nor PrP ko
      mice were susceptible when inoculated intracerebrally (i.c.) or orally with CWD
      brain material (scrapie pool from six mule deer) and followed for 600+ days
      (dpi). Deer PrP tg mice were not susceptible to i.c. inoculation with murine
      scrapie. In contrast, a fatal neurologic disease occurred accompanied by
      conversion of deer PrPsen to PrPres by western blot and immunohistochemistry
      after either i.c. inoculation with CWD brain into two lines of tg mice studied
      (312+32 dpi [mean+2 standard errors] for the heterozygous tg line 33, 275+46 dpi
      for the heterozygous tg line 39 and 210 dpi for the homozygous tg line 33) or
      after oral inoculation (381+55 dpi for the homozygous tg line 33 and 370+26 dpi
      for the homozygous tg line 39). Kinetically, following oral inoculation of CWD
      brain, PrPres was observed by day 200 when mice were clinically healthy in the
      posterior surface of the dorsum of the tongue primarily in serous and mucous
      glands, in the intestines, in large cells at the splenic marginal zone that
      anatomically resembled follicular dendritic cells and macrophages and in the
      olfactory bulb and brain stem but did not occur in the cerebellum, cerebral
      cortex or hippocampus or in hearts, lungs and livers of infected mice. After 350
      days when mice become clinically ill the cerebellum, cerebral cortex and
      hippocampus became positive for PrPres and displayed massive spongiosis, neuronal
      drop out, gliosis and florid plaques.

PMID- 17451774
TI  - Cloning and analysis of microRNAs encoded by the primate gamma-herpesvirus rhesus
      monkey rhadinovirus.
AB  - Several pathogenic human herpesviruses have recently been shown to express
      virally encoded microRNAs in infected cells. Although the function of these
      microRNAs is largely unknown, they are hypothesized to play a role in mediating
      viral replication by downregulating cellular mRNAs encoding antiviral factors.
      Here, we report the cloning and analysis of microRNAs encoded by Rhesus Monkey
      Rhadinovirus (RRV), an animal virus model for the pathogenic human gamma
      herpesvirus Kaposi's Sarcoma-Associated Herpesvirus (KSHV). RRV expresses several
      microRNAs that are encoded in the same genomic location as the previously
      reported KSHV microRNAs, yet these microRNAs are unrelated in primary sequence.
      These data set the stage for the mutational ablation and phenotypic analysis of
      RRV mutants lacking one or more viral microRNAs.

PMID- 17451775
TI  - Latitude-of-birth and season-of-birth effects on human color vision in the
      Arctic.
AB  - Extreme natural ambient light reduction, in both energy and range of wavelength
      spectrum, occurs during the winter season at very high latitudes (above the
      Arctic Circle or 66 degrees 32' North) that in turn results in increased exposure
      to artificial lighting. In contrast, during the summer months, the sun remains
      above the horizon and there is no darkness or night. Little is known about these
      extreme changes in light exposure on human visual perception. Measuring color
      discriminations with the FM100 Test revealed that Norwegians born above the
      Arctic Circle were less sensitive to yellow-green, green, and green-blue spectrum
      differences whereas they were more sensitive to hue variations in the purple
      range than individuals born below the Arctic Circle. Additionally, it was found
      that the Norwegian individuals born above the Arctic Circle and during autumn
      showed an overall decrease in color sensitivity, whereas those born in the summer
      showed a relative increase. All participants were adults and their color vision
      was tested in the same location (i.e., in Tromso at 69.7 degrees North). These
      findings are consistent with the idea that there is a measurable impact on colour
      vision as adults of the photic environment that individuals born above the Arctic
      Circle and in the autumn experienced during infancy, namely a reduction in
      exposure to direct sunlight and an increase in exposure to twilight and
      artificial lighting.

PMID- 17451776
TI  - Orientation repulsion and attraction in alignment perception.
AB  - Orientation masking induces changes of discrimination thresholds and perceived
      orientation. Studies on alignment discrimination of Vernier stimuli concentrated
      on masking induced changes of discrimination thresholds, without considering
      possible changes of perceived orientation and/or alignment of the two-line
      segments. Measuring both parameters in an orientation discrimination task, we
      confirmed a standard repulsion effect between a single line target and a mask
      grating that co-varied with elevated orientation discrimination thresholds.
      Masking a Vernier stimulus in an alignment discrimination task, we observed a
      strong misperception of alignment that was accompanied with elevated alignment
      discrimination thresholds. Orientation masking on perceived orientation and
      alignment of a Vernier stimulus revealed orientation repulsion and attraction
      that depended on the spatio-orientation configuration of the superimposed
      stimuli. Control of task-dependent effects confirmed that our observed pattern of
      results was independent of attentional or cognitive demands.

PMID- 17451777
TI  - The path of least persistence: object status mediates visual updating.
AB  - On what basis does the visual system use recently sampled information to update
      existing representations of the world? One possibility is that representations
      are updated through an image-based point-for-point replacement process. An
      alternative possibility is that representations are updated on the basis of
      perceptually organized units that reflect objects in the scene rather than
      locations within the visual field. We report a new effect involving a modulation
      of visible persistence that seems to support this alternative possibility. In
      particular, we show that a moving stimulus leaves a visible trace of itself when
      it undergoes an abrupt and transient change in size but does not do so when the
      stimulus does not change. Further we show that this effect is substantially
      reduced when a scene-based reason for the abrupt change in size is provided
      (i.e., the object is shown to be passing behind an occluding surface that has a
      very small window in it through which the stimulus shows briefly). We suggest
      that the visible persistence in the face of change reflects a disruption of the
      normal updating process which is object-based and disrupted because of the
      discontinuity of the object. Providing a scene-based reason for the discontinuity
      allows the object representation to be maintained, and thus does not result in a
      disruption of the updating process.

PMID- 17451778
TI  - Population structure of Cladophora-borne Escherichia coli in nearshore water of
      Lake Michigan.
AB  - We previously reported that the macrophytic green alga Cladophora harbors high
      densities (up to 10(6) colony-forming units/g dry weight) of the fecal indicator
      bacteria, Escherichia coli and enterococci, in shoreline waters of Lake Michigan.
      However, the population structure and genetic relatedness of Cladophora-borne
      indicator bacteria remain poorly understood. In this study, 835 E. coli isolates
      were collected from Cladophora tufts (mats) growing on rocks from a breakwater
      located within the Indiana Dunes National Lakeshore in northwest Indiana. The
      horizontal fluorophore enhanced rep-PCR (HFERP) DNA fingerprinting technique was
      used to determine the genetic relatedness of the isolates to each other and to
      those in a library of E. coli DNA fingerprints. While the E. coli isolates from
      Cladophora showed a high degree of genetic relatedness (92% similarity), in most
      cases, however, the isolates were genetically distinct. The Shannon diversity
      index for the population was very high (5.39). Both spatial and temporal
      influences contributed to the genetic diversity. There was a strong association
      of isolate genotypes by location (79% and 80% for lake- and ditch-side samplings,
      respectively), and isolates collected from 2002 were distinctly different from
      those obtained in 2003. Cladophora-borne E. coli isolates represented a unique
      group, which was distinct from other E. coli isolates in the DNA fingerprint
      library tested. Taken together, these results indicate that E. coli strains
      associated with Cladophora may be a recurring source of indicator bacteria to the
      nearshore beach.

PMID- 17451779
TI  - Solids characterisation in an anaerobic migrating bed reactor (AMBR) sewage
      treatment system.
AB  - The aim of this work was to characterise the solids in an anaerobic sewage
      treatment process. Hindered settling velocity, particle size distributions (PSD),
      influent and effluent COD(P)/SS and discrete settling velocity distributions were
      all measured. The anaerobic migrating bed reactor (AMBR) solids were mainly
      flocculent and had a settling rate equivalent to a good settling activated sludge
      ( approximately SSVI=60 mL/g). The PSD of the anaerobic solids were very
      different to PSD for activated sludge flocs, with the anaerobic solids having a
      modal size an order of magnitude smaller than activated sludge, but a range of
      particle sizes being two orders of magnitude larger. There was a far greater
      range in size and structure in the anaerobic solids. The anaerobic process solids
      were primarily feed solids undergoing VSS destruction (hydrolysis). The
      biological mass was small. The solids seemed to retain their size as the
      volatiles were degraded and the density decreased ('skeletons' of the influent
      particulates). The small fraction of slowly settling solids, which have been
      identified to have a similar modal size but lower density than the mixed solids
      in the reactor, pose a solids retention time (SRT) control problem when relying
      on settling alone for solids retention.

PMID- 17451780
TI  - Cost-efficient operation of a denitrifying activated sludge process.
AB  - In this paper, the choice of optimal set-points and cost minimizing control
      strategies for the denitrification process in an activated sludge process are
      treated. In order to compare different criterion functions, simulations utilizing
      the COST/IWA simulation benchmark are considered. By means of operational maps
      the results are visualized. It is found that it is easy to distinguish set-point
      areas where the process can be said to be efficiently controlled in an economic
      sense. The characteristics of these set-point areas depend on the chosen effluent
      nitrate set-point as well as the distribution of the different operating costs.
      It is also discussed how efficient control strategies may be accomplished.

PMID- 17451781
TI  - Athermal microwave effects for enhancing digestibility of waste activated sludge.
AB  - A bench scale industrial microwave (MW) unit equipped with fiber optic
      temperature and pressure controls within pressure sealed vessels successfully
      simulated conventional heating (CH, in water bath). By identical temporal heat
      temperature profiles for waste activated sludge (WAS) samples, evaluation of the
      athermal effects of MW irradiation on WAS floc disintegration and anaerobic
      digestion was achieved. In a pretreatment range of 50-96 degrees C, both MW and
      CH WAS samples resulted in similar particulate chemical oxygen demand (COD) and
      biopolymer (protein and polysaccharide) solubilization and there was no
      discernable MW athermal effect on the COD solubilization of WAS. However,
      biochemical methane potential (BMP) tests showed improved biogas production for
      MW samples over CH samples indicating that the MW athermal effect had a positive
      impact on the mesophilic anaerobic biodegradability of WAS. BMP tests also showed
      that despite mild inhibition in the first 7d, MW acclimated inoculum digesting
      pretreated (to 96 degrees C) WAS, produced 16+/-4% higher biogas compared to the
      control after 15 d of mesophilic batch digestion. However, initial acute
      inhibition was more severe for non-acclimated inoculum requiring recovery time
      that was two times longer with only 4+/-0% higher biogas production after 17d.
      Inoculum acclimation not only accelerated the production of biogas, but also
      increased the extent of the ultimate mesophilic biodegradation of MW irradiated
      WAS (after 15-27 d).

PMID- 17451782
TI  - Effects of chemical sludge disintegration on the performances of wastewater
      treatment by membrane bioreactor.
AB  - A new wastewater treatment process combining a membrane bioreactor (MBR) with
      chemical sludge disintegration was tested in bench scale experiments. In
      particular, the effects of the disintegration treatment on the excess sludge
      production in MBR were investigated. Two MBRs were operated. In one reactor, a
      part of the mixed liquor was treated with NaOH and ozone gas consecutively and
      was returned to the bioreactor. The flow rate of the sludge disintegration stream
      was 1.5% of the influent flow rate. During the 200 days of operation, the MLSS
      level in the bioreactor with the disintegration treatment was maintained
      relatively constant at the range of 10,000-11,000 mg/L while it increased
      steadily up to 25,000 mg/L in the absence of the treatment. In the MBR with the
      sludge disintegration, relatively constant transmembrane pressures (TMPs) could
      be maintained for more than 6 months while the MBR without disintegration showed
      an abrupt increase of TMP in the later phase of the operation. In conclusion, a
      complete control of excess sludge production in the membrane-coupled bioreactor
      was possible without significant deterioration of the treated water quality and
      membrane performances.

PMID- 17451783
TI  - Effects of four rice herbicides on some metabolic and toxicology parameters of
      teleost fish (Leporinus obtusidens).
AB  - Effects of different herbicides on acetylcholinesterase (AChE), catalase and
      TBARS formation in teleost fish (Leporinus obtusidens) were studied. Fish were
      exposed during 30 days at concentrations of herbicides used in rice field. AChE
      activity in the brain decreased significantly after exposure to the herbicides
      clomazone and quinclorac. However, AChE activity increased significantly in
      muscle tissue after exposure to clomazone, propanil and metsulfuron methyl. Fish
      exposed to quinclorac, propanil and metsulfuron methyl showed TBARS decreased
      levels in brain and muscle tissues. However, TBARS and catalase activity
      increased in liver tissue after clomazone and propanil exposure. This study
      pointed out long-term effects on AChE activity, oxidative stress and antioxidant
      enzyme catalase in tissues of L. obtusidens after exposure to environmentally
      relevant concentrations of rice field herbicides. These parameters have been used
      to monitor fish toxicity in rice field system.

PMID- 17451785
TI  - Recovery and characterization of the humate-like salified polymeric organic
      fraction (lignimerin) from Kraft cellulose mill wastewater.
AB  - A dark and complex salified organic polymeric mixture, named lignimerin, was for
      the first time recovered from Kraft cellulose mill wastewater (KCMW) and
      characterized by chemical, spectroscopic and relative molecular weight (RMW)
      analysis. Lignimerin proved to be composed of polyphenols (57.00%), carbohydrates
      (22.26%) and proteins (7.42%). It also contained metals (6.93%), mainly Ca and,
      to much lower extent, Mg, Na, Al, Fe, K, Mn, Zn and Cu, bound to the carboxylate
      and phenate groups. The distribution of lignimerin RMW was assessed to be
      approximately between 1000 and 8600Da, as well as to consist of lignin and
      tannin, protein and polysaccharide moieties, strongly aggregated each other. H
      lignimerin, its acid derivative, revealed a chemical composition and a RMW
      distribution very close to that of lignimerin, but a marked metal cations
      decreasing (1.60%) with respect to lignimerin (6.93%). The humic acid-like nature
      of both the polymers was assessed. Their potential use as bio-adsorbents of heavy
      metals is briefly discussed.

PMID- 17451786
TI  - Evidence for new Neanderthal teeth in Tabun Cave (Israel) by the application of
      self-organizing maps (SOMs).
AB  - Morphological and metrical study suggested that seven human teeth from Tabun
      Cave, Israel were part of the upper dentition of a single, probably Neanderthal,
      individual renumbered as Tabun BC7. An enamel fragment gave ESR age estimates of
      82+/-14 ka (early U-uptake) and 92+/-18 ka (linear uptake) and an age estimate of
      90(+30)(-16) ka using U-series disequilibrium. Although metrical analyses
      suggested Neanderthal affinities, definitive assessment was difficult as the
      values often fell into the ranges of both Neanderthal and Levantine early modern
      human samples. Therefore, two further classification analyses were conducted
      (neural networks using self-organizing maps and homogeneity analysis). Both
      identify Tabun BC7 as a Neanderthal. Neural networks are a promising tool for
      paleoanthropological studies as they can provide reliable classifications even
      with incomplete data.

PMID- 17451787
TI  - Male rats exhibit higher oxidative protein damage than females of the same
      chronological age.
AB  - The basis of the difference in life expectancy between males and females is still
      unknown. Previous studies have provided compelling evidence for the presence of
      oxidized proteins, and lipids in advanced human atherosclerotic lesions. The
      gender factor responsible for such protein oxidation is unknown and
      controversial. Our aim was to reveal the difference between protein oxidation
      parameters of male and female rats of the same chronological age to understand
      the protein oxidation mechanisms enabling females live longer than males. In the
      current study, we investigated the relation between protein hydroperoxide levels
      (P-OOH) and other protein oxidation parameters such as protein carbonyl (PCO),
      total thiol (T-SH), advanced oxidation protein products (AOPP), and nitrotyrosine
      (NT). Our study also covered other oxidative stress parameters such as lipid
      hydroperoxides (L-OOH), and superoxide dismutase (SOD) activity in the plasma of
      male and female aged rats. Plasma P-OOH and AOPP levels of male rats were
      significantly higher compared with those of the female rats. T-SH levels were
      significantly lower in the aged male rats compared with those of the female rats.
      On the other hand, PCO, NT, and L-OOH levels, and SOD activity were all found to
      be not different. These data support the hypothesis that elevated levels of P-OOH
      and AOPP contribute to the extent of protein, but not lipid, oxidation in plasma
      of aged male rats. Furthermore, the results presented here may also rationalize
      studies, which have shown that protein oxidation is modulated on the basis of
      gender dependency.

PMID- 17451788
TI  - Impact of NOx reduction on long-term ozone trends in an urban atmosphere.
AB  - We investigated the relationships between ambient O(3) concentrations and the
      concentrations of its precursors, NO(x) and NMHC, in Osaka, Japan. The levels of
      O(x)' (where [O(x)']=[O(3)]+[NO(2)]-0.1x[NO(x)] where the last term accounts for
      primary emissions of NO(2)) were uniform within the city even in the
      photochemically active season. We suggested that NO oxidation by peroxy radicals
      was a minor contributor, and that oxidation of locally emitted NO by background
      O(3) in the city was the primary control on NO(2) concentrations. Ozone
      concentrations increased linearly from 1985 to 2002 at a rate of 0.6 ppbv/yr,
      even though O(x)' concentrations remained constant after the mid 1990s. The trend
      for O(x)' concentrations could not be explained in terms of an increase in local
      O(3) production, and the trend was found to reflect background O(3)
      concentrations in Japan. There was a clear relationship between the NO(2)/O(x)'
      ratio and NO(x) concentration: the ratio decreased with decreasing NO(x)
      concentration. As a consequence, O(3) increased with decreasing NO(x)
      concentration. The reduction of NO(x) emissions was deemed to be an important
      factor for the recent trend of increasing O(3) concentrations in Osaka City.

PMID- 17451789
TI  - Delayed effects of environmentally relevant concentrations of 3,3',4,4'
      tetrachlorobiphenyl (PCB-77) and non-polar sediment extracts detected in the
      prolonged-FETAX.
AB  - In the prolonged-FETAX (prolonged-Frog Embryo Teratogenic Assay-Xenopus) tadpoles
      are allowed to develop until metamorphosis after an initial 4 day early life
      stage exposure (FETAX). PCB 77 (3,4,3',4'-tetrachlorobiphenyl) and sediment
      extracts were used in the presented experiments. Concentrations of PCB 77 (0.03
      nM=8.55 ng/L; 3 nM=855 ng/L; 300 nM=85.5 microg/L, 30,000 nM=8.55 mg/L) were
      derived on the basis of dioxin-like toxic equivalency concentrations known to be
      present in pore-water. The results were compared to those obtained with the
      standard FETAX. In the prolonged-FETAX the percentage of animals passing
      metamorphosis within 115 days was significantly decreased in the groups exposed
      to 300 or 30,000 nM PCB 77. Significantly increased percentages of tadpoles were
      halted in thyroid hormone dependent early metamorphic NF stages <or=55 (3 nM PCB
      77) and metamorphic stages 56-60 tadpoles (300 nM PCB 77 and 30,000 nM PCB 77).
      Non-polar sediment extracts from two contaminated Dutch sites significantly
      decreased, and one significantly increased the percentage of animals that passed
      metamorphosis. These results were in accordance with earlier in vitro results in
      a thyroid hormone dependent assay and strongly suggest the presence of thyroid
      hormone disrupting compounds in the aquatic environment. In the classical FETAX
      neither PCB 77 nor non-polar sediment extracts induced any effects. The results
      of the present study indicate that the prolonged-FETAX is an important in vivo
      tool in addition to the in vitro T-screen to assess long-term effects of early
      life-stage exposure to environmentally relevant concentrations of (mixtures of)
      compounds and that affect thyroid hormone dependent physiology.

PMID- 17451790
TI  - Low-temperature formation and degradation of chlorinated benzenes, PCDD and PCDF
      in dust from steel production.
AB  - Dust from thermal processes may catalytically enhance the formation of
      chlorinated aromatic compounds under oxygen-rich conditions. The activities of
      two dust samples from electric arc furnaces and one from iron ore-based
      steelmaking (oxygen converter) were investigated in a laboratory experiment. The
      dust samples were heated at 300 degrees C for 2 h in an air atmosphere. The
      concentrations of chlorinated benzenes did not change greatly upon heating, while
      the concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans
      decreased. The addition of copper in parallel runs resulted in a substantial
      increase in the concentration of chlorinated benzenes, thus indicating that the
      experimental setup was suitable for the evaluation of low-temperature catalysis.
      The outcome of the experiment seems to suggest that results cannot easily be
      extrapolated between different thermal and metallurgical processes. Some measures
      to reduce emissions, such as inhibition of catalytic activity and rapid cooling,
      could possibly be counterproductive when applied to off-gases from the
      steelmaking processes investigated here.

PMID- 17451792
TI  - Experimental arterial thrombosis regulated by androgen and its receptor via
      modulation of platelet activation.
AB  - OBJECTIVES: The aim of our study is to elucidate whether experimental arterial
      thrombosis is regulated by physiological doses of androgen and its receptor via
      modulation of platelet activation. METHODS: Surgical castration was performed in
      male rats and ferric chloride (FeCl(3)), as a stimulator, induced the
      experimental arterial thrombosis. Testosterone was measured directly by
      chemiluminescent immunoassay on the Bayer ADVIA Centaur analyzer.
      Dihydrotestosterone (DHT) was determined by ELISA using a commercially available
      kit. A platelet aggregometer was used to assess aggregation, and a platelet
      adherometer was used to measure adhesion. The contents of TXB(2) and 6-Keto
      PGF(1alpha) were assayed by radio-immunoassay using commercially available kits.
      RESULTS: Our data showed that DHT replaced restored circulating DHT of castrated
      rats to physiological levels, without being altered by treatment with flutamide.
      Castration caused significant increases in the thrombus area and weight in
      castrated rats as compared with control group. In PRP diluted with autologous
      PPP, ADP-induced platelet aggregation rate was only 9.10%. However, in PRP
      diluted with Tyrode's buffer, 1 microM ADP-induced platelet aggregation rate rose
      to 63.65%. In PRP diluted with Tyrode's buffer, and pretreated with DHT (1 nM, 2
      nM), ADP-induced platelet aggregation was significantly lowered again. Platelet
      aggregation in PRP diluted with autologous PPP was enhanced in castrated rats as
      compared with sham-operated rats, and DHT (2 nM) replacement suppressed platelet
      aggregation in castrated PRP to the level similar to that of sham-operated rats.
      However, presence of flutamide (3 microM) significantly increased platelet
      aggregation in PRP diluted with autologous PPP or Tyrode's buffer. DHT (2 nM)
      replacement significantly inhibited the ADP-induced platelet adhesion. However,
      presence of flutamide (3 microM) increased ADP-induced platelet adhesion again.
      DHT replacement obviously reduced the ratio of TXB(2) to 6-keto-PGF(1alpha) in
      castrated rats. However, administration of flutamide and DHT to castrated rats
      caused an increase in the ratio of TxB(2) to 6-keto-PGF1alpha. CONCLUSION:
      Inhibition of experimental arterial thrombosis by androgen at physiological doses
      and its receptor is mediated via modulation of platelet activation.

PMID- 17451793
TI  - The relationship between nutrition and circadian rhythms in mammals.
AB  - The master clock located in the suprachiasmatic nuclei (SCN) of the anterior
      hypothalamus regulates circadian rhythms in mammals. The clock is an
      intracellular, transcriptional mechanism sharing the same molecular components in
      SCN neurons and in peripheral cells, such as the liver, intestine, and retina.
      The circadian clock controls food processing and energy homeostasis by regulating
      the expression and/or activity of enzymes involved in cholesterol, amino acid,
      lipid, glycogen, and glucose metabolism. In addition, many hormones involved in
      metabolism, such as insulin, glucagon, adiponectin, corticosterone, leptin, and
      ghrelin, exhibit circadian oscillation. Furthermore, disruption of circadian
      rhythms is involved in the development of cancer, metabolic syndrome, and
      obesity. Metabolism and food intake also feed back to influence the biological
      clock. Calorie restriction (CR) entrains the SCN clock, whereas timed meals
      entrain peripheral oscillators. Furthermore, the cellular redox state, dictated
      by food metabolism, and several nutrients, such as glucose, ethanol, adenosine,
      caffeine, thiamine, and retinoic acid, can phase-shift circadian rhythms. In
      conclusion, there is a large body of evidence that links feeding regimens, food
      components, and the biological clock.

PMID- 17451794
TI  - 3-O-Formyl-20R,21-epoxyresibufogenin suppresses IL-6-type cytokine actions by
      targeting the glycoprotein 130 subunit: potential clinical implications.
AB  - BACKGROUND: The multifunctional inflammatory cytokine IL-6 regulates the acute
      phase reaction and plays central roles in the pathogenesis of chronic
      inflammatory disorders. OBJECTIVES: Two small chemical compounds, 3-O-formyl
      20R,21-epoxyresibufogenin (TB-2-081) and 3-O-formyl-20S,21-epoxyresibufogenin (TB
      2-082), known isolates from the Chinese toad skin extract drug Ch'an Su, were
      synthesized and tested on the IL-6-induced hepatic acute-phase reaction. METHODS:
      HepG2 cells or rat primary hepatocytes were incubated with the compounds, and the
      effects on IL-6-induced expression of acute-phase molecules were tested. RESULTS:
      TB-2-081, and to a lesser extent TB-2-082, suppressed IL-6-induced alpha1
      antichymotrypsin (AACT) mRNA expression in HepG2 cells, whereas TB-2-081 failed
      to influence the mRNA expression of the TNF-alpha-induced mRNA expression of the
      methionine adenosyltransferase 2A gene in these cells. TB-2-081 suppressed IL-6
      induced mRNA expression of alpha1-acid glycoprotein, alpha2-macroglobulin, and
      beta-fibrinogen in and secretion of the C-reactive protein by rat primary
      hepatocytes. TB-2-081 shifted the IL-6 dose-response curve of the AACT mRNA
      expression right and downward and inhibited IL-6-induced phosphorylation of
      signal transducer and activator of transcription 3. In addition to IL-6, TB-2-081
      inhibited IL-11-stimulated and oncostatin M-stimulated AACT mRNA expression
      independently of the IL-6 receptor subunit. The soluble glycoprotein 130, but not
      the soluble IL-6 receptor, antagonized TB-2-081-induced suppression of IL-6
      stimulated AACT mRNA expression. CONCLUSION: TB-2-081 inhibits IL-6-type cytokine
      action by attenuating the function of the common receptor subunit glycoprotein
      130. CLINICAL IMPLICATIONS: This class of compounds may be beneficial for the
      treatment of diseases in which excessive circulation/production/action of IL-6
      type cytokines play pathologic roles.

PMID- 17451795
TI  - Eosinophils in the new millennium.

PMID- 17451796
TI  - Placebo response in asthma: a robust and objective phenomenon.
AB  - BACKGROUND: Placebos are hypothesized to exert positive effects on medical
      conditions by enhancing patient expectancies. Recent reviews suggest that placebo
      benefits are restricted to subjective responses, like pain, but might be
      ineffective for objective physiologic outcomes. Nevertheless, mind-body links and
      placebo responsivity in asthma are widely believed to exist. OBJECTIVE: We
      carried out a randomized, double-blind investigation to (1) determine whether
      placebo can suppress airway hyperreactivity in asthmatic subjects, (2) quantify
      the placebo effect, (3) identify predictors of the placebo response, and (4)
      determine whether physician interventions modify the placebo response. METHODS:
      In a double-blind, crossover design investigation, 55 subjects with mild
      intermittent and persistent asthma with stable airway hyperreactivity were
      randomized to placebo or salmeterol before serial methacholine challenges.
      Subjects were additionally randomized to physician interactions that communicated
      either positive or neutral expectancies regarding drug effect. RESULTS: Placebo
      bronchodilator administration significantly reduced bronchial hyperreactivity
      compared with baseline (the calculated concentration of methacholine required to
      induce a 20% decrease in FEV(1) nearly doubled); 18% of subjects were placebo
      responders by using conservative definitions. Experimental manipulation of
      physician behavior altered perceptions of the physician but not the magnitude or
      frequency of the placebo response. CONCLUSIONS: Objective placebo effects exist
      in asthma. These responses are of significant magnitude and likely to be
      meaningful clinically. The placebo response was not modulated by alterations in
      physician behavior in this study. CLINICAL IMPLICATIONS: The placebo response in
      patients with asthma is important in understanding the limitations of clinical
      research studies and in maximizing safe and effective therapies. This article
      confirms the existence of a strong placebo response in an objective and
      clinically relevant measure of disease activity.

PMID- 17451797
TI  - Design flaws plus delivery flaws equal faux conclusions.

PMID- 17451798
TI  - Immunomodulatory effects of aqueous birch pollen extracts and phytoprostanes on
      primary immune responses in vivo.
AB  - BACKGROUND: We recently demonstrated that pollen not only function as allergen
      carriers but also as rich sources of bioactive lipids, such as phytoprostanes,
      that modulate human dendritic cell (DC) function in a way that results in an
      enhanced T(H)2 polarization in vitro. OBJECTIVE: Here we analyzed the
      immunomodulatory capacities of Betula alba (white birch) aqueous pollen extracts
      (Bet-APEs) and pollen-associated phytoprostanes in the murine system in vitro and
      in vivo. METHODS: DC function was analyzed in vitro by using BALB/c bone marrow
      derived DCs. T-cell responses were analyzed with DO11.10 peptide 323-339 from
      chicken ovalbumin (OVA)-specific CD4 T cells as responder cells. For in vivo
      studies, OVA-specific CD4 T cells were adoptively transferred into BALB/c mice.
      Twenty-four hours later, mice were challenged by means of intranasal application
      of OVA in the absence or presence of Bet-APEs or phytoprostanes. Polarization of
      T-cell responses in vivo was analyzed in draining lymph node cells. RESULTS: In
      vitro Bet-APEs and E(1)-phytoprostanes dose-dependently inhibited LPS-induced IL
      12p70 of DCs. In addition, Bet-APEs induced a T(H)2 polarization in vitro.
      Similarly, intranasal instillation of Bet-APEs in vivo, together with the
      antigen, lead to increased IL-4, IL-5, and IL-13 secretion and decreased IFN
      gamma secretion from antigen-specific T cells in the draining lymph nodes. In
      contrast, intranasal E1- and F1-phytoprostanes downregulated both T(H)1 and T(H)2
      cytokine production in vivo. CONCLUSION: Pollen release water-soluble factors
      that display T(H)2-polarizing capacities in vivo independently of E(1)- and F(1)
      phytoprostanes. CLINICAL IMPLICATIONS: Identification of the underlying
      mechanisms might open new approaches for pharmacologic intervention.

PMID- 17451799
TI  - Eosinophilia in systemic mastocytosis: clinical and molecular correlates and
      prognostic significance.
AB  - BACKGROUND: In a group of patients with systemic mastocytosis (SM), marked and
      sustained eosinophilia is detectable (SM-eo). OBJECTIVE: Although the molecular
      defect has been defined in some cases, little is known about the impact and
      clinical correlates of eosinophilia. METHODS: In a cohort of 63 patients with SM,
      we identified 9 with permanent eosinophilia (>1500/microL). According to the
      World Health Organization classification, 2 had indolent SM, 1 had smoldering SM,
      2 had SM with associated chronic eosinophilic leukemia (SM-CEL), and 4 had
      aggressive SM. RESULTS: SM-eo was found to be associated with a significantly
      reduced probability of overall and event-free survival compared with SM without
      eosinophilia (P < .05). In the 2 patients with SM-CEL, a CHIC2 deletion was
      found. By contrast, no KIT mutation at codon 816 was detectable in these
      patients. In the other patients with SM-eo, KIT D816V was demonstrable. The 2
      patients with SM-CEL had cardiomyopathy, whereas other organ systems remained
      largely unaffected. By contrast, in all other patients with SM-eo, organopathy,
      if recorded, affected the bone marrow, liver, or/and skeletal system, but not the
      heart, even when eosinophilia persisted for many years. CONCLUSIONS: The
      biochemical basis of eosinophilia in SM is variable and predictive for the type
      of organopathy. CLINICAL IMPLICATIONS: In SM eosinophilia is of prognostic
      significance but is not a final diagnosis and is not invariably associated with
      cardiomyopathy. The latter might be restricted to cases with an associated
      primary eosinophilic disorder (SM-CEL).

PMID- 17451800
TI  - Treatment of airway inflammation improves exercise pulmonary gas exchange and
      performance in asthmatic subjects.
AB  - BACKGROUND: Asthma is an inflammatory disease of the airways that can lead to
      impaired arterial blood oxygenation during exercise. OBJECTIVE: We asked whether
      treatment of airway inflammation in asthmatic subjects would improve arterial
      blood gases during whole-body exercise. METHODS: By using a double-blind parallel
      group design, 19 asthmatic subjects completed treadmill exercise to exhaustion on
      2 occasions: (1) before and (2) after 6 weeks' treatment with an inhaled
      corticosteroid (ICS; n = 9) or placebo (n = 10). RESULTS: The ICS group had
      improved resting pulmonary function, decreased exercise-induced bronchospasm, and
      decreased postexercise sputum histamine during the posttreatment study compared
      with that during the pretreatment study. In the ICS group exercise Pao(2) was
      significantly increased after treatment (84.8 to 93.8 mm Hg). Increased alveolar
      ventilation (arterial Pco(2) decreased from 36.9 to 34.1 mm Hg) accounted for 37%
      of the increased Pao(2) and improved gas exchange efficiency (alveolar-to
      arterial Po(2) difference decreased from 22.5 to 16.3 mm Hg) accounted for the
      remaining 63% of the increased Pao(2) after treatment. In the ICS group exercise
      time to exhaustion was increased from 9.9 minutes during the pretreatment study
      to 14.8 minutes during the posttreatment study. CONCLUSION: Treatment of airway
      inflammation in asthmatic subjects can improve arterial blood oxygenation during
      exercise by (1) improving airway function, thereby allowing increased alveolar
      ventilation during exercise, and (2) improving the efficiency of alveolar-to
      arterial blood O(2) exchange. CLINICAL IMPLICATIONS: In asthmatic patients ICSs
      not only attenuate exercise-induced bronchospasm but also improve arterial blood
      oxygenation during exercise.

PMID- 17451801
TI  - Persistence of proinflammatory response after severe respiratory syncytial virus
      disease in children.

PMID- 17451802
TI  - Prevalence of self-reported food allergy in American adults and use of food
      labels.
AB  - BACKGROUND: Few population-based studies in the United States have determined the
      prevalence of food allergy in adults and the problems these individuals might
      have with reading food labels. OBJECTIVE: The objectives of this study are to
      report the prevalence of self-reported food allergy, to identify the
      characteristics of food allergy reactions, and to describe the use of labels
      among adults with food allergy. METHODS: Questions from the US Food and Drug
      Administration's 2001 Food Safety Survey were analyzed to determine the
      prevalence of food allergy and opinions about food labels in the management of
      food allergy. RESULTS: The prevalence of self-reported food allergy is 9.1% among
      all survey respondents, with 5.3% of all respondents reporting a doctor-diagnosed
      food allergy. The prevalence of food allergy to the 8 most common allergens
      (peanut, tree nuts, egg, milk, wheat, soybeans, fish, and crustacean shellfish)
      is self-reported as 2.7% among respondents with doctors' diagnoses. Several label
      issues, such as words on some ingredient lists being too technical or hard to
      understand and food labels not always alerting persons to new ingredients, were
      reported as serious or very serious obstacles for managing an allergy.
      CONCLUSION: The prevalence of self-reported doctor-diagnosed food allergy among
      US adults is 5.3%, and a large portion of adults with food allergy found certain
      label issues a serious problem for managing their food allergy. CLINICAL
      IMPLICATIONS: The findings provide a needed source of population-based prevalence
      data of food allergy among US adults. Label issues identified are useful in
      understanding the difficulties of managing a food allergy.

PMID- 17451803
TI  - Acute asthma intervention: insights from the STAY study.
AB  - In some patients, asthma control is improved by combining inhaled corticosteroids
      with long-acting beta(2)-agonists. However, fluctuating asthma control and
      exacerbations can still occur. The STAY study evaluated whether, in patients with
      moderate to severe asthma, replacing a short-acting beta(2)-agonist reliever with
      the combination of budesonide/formoterol as reliever would both provide rapid
      symptom relief and reduce asthma exacerbations. The study evaluated 2760 patients
      with asthma (4-80 years) randomized to budesonide 400 microg twice daily (bid)
      and terbutaline as reliever, budesonide/formoterol 100/6 microg bid and
      terbutaline as reliever, or budesonide/formoterol 100/6 microg bid both as
      maintenance and reliever. Children (age 4-11 years) used a once-daily maintenance
      dose. Budesonide/formoterol as maintenance and reliever significantly reduced
      severe exacerbation risk by 45% to 47% compared with the other 2 treatments and
      improved symptoms, awakenings, and lung function. The benefit was seen in
      patients of all ages. Subsequent studies have revealed that this beneficial
      effect of budesonide/formoterol as maintenance and reliever requires both
      components of the combination.

PMID- 17451804
TI  - Obesity prevention in schools: current role and future practice of school nurses.
AB  - OBJECTIVE: To determine responsibilities of school nurses in delivering obesity
      prevention services, assess opinions and beliefs about school-based obesity
      prevention and determine factors associated with school nurses supporting and
      providing obesity prevention services. METHOD: In fall 2005, a self-administered
      survey was mailed to 275 school nurses in Minnesota; 221 were returned (response
      rate=80%). RESULTS: Most (76%) school nurses supported the use of school health
      services (SHS) for obesity prevention. The likelihood of nurses supporting SHS
      for obesity prevention (p=0.009), as well as performing more child- (p=0.016) and
      school-level (p = < 0.001) obesity prevention tasks increased as perceived
      support for school-based obesity prevention from health care providers and school
      administrators, teachers and foodservice staff increased. Nurses supportive of
      school-based height, weight and BMI screening and parent notification were twice
      as likely to perform child-level obesity prevention tasks (p=0.021) and more than
      three times as likely to support using SHS for obesity prevention (p=0.005).
      CONCLUSION: Our study suggests considerable support among school nurses for
      school-based obesity prevention efforts and a growing interest in providing
      primary and secondary preventive care services in the school setting. Study
      findings also speak to the need for preparation, time and support from the school
      and health provider community.

PMID- 17451805
TI  - Artificial insemination in the anoestrous and the postpartum white rhinoceros
      using GnRH analogue to induce ovulation.
AB  - The objective of this study was to develop AI and to achieve first time pregnancy
      in a nulliparous rhinoceros. For this, one 24-year-old irregular cycling female
      white rhinoceros was selected, which had never been mated. The endocrine function
      was monitored by faecal and serum pregnane analysis. Ultrasound determined the
      optimal day for AI by measuring follicle sizes of 2.0, 2.6, 3.0, 3.2 cm on days 
      6, -4, -1, 0 of the induced oestrous cycle, respectively. AI was performed and
      ovulation induced when a pre-ovulatory-sized follicle was present using GnRH
      analogue, deslorelin. Fresh semen was deposited in the uterine horn using a
      patented AI catheter overcoming the hymeneal membrane and torturous cervical
      folds non-surgically. Moreover, ultrasound monitoring of the uterine involution
      and ovarian activity on days 16, 26, 30 postpartum facilitated the induction of
      and the AI on the first postpartum oestrous in a rhinoceros using GnRH analogue.
      Two consecutive pregnancies were achieved by AI for the first time in the
      rhinoceros. Pregnancies were diagnosed by elevated serum and faecal 20-oxo
      pregnane concentrations. In addition ultrasound measured biometric parameters of
      the two foetuses on days 86 and 133 of gestation. Two female calves were born
      after 490 and 502 days of gestation, yet one calf was stillborn. AI in rhinoceros
      might now be used as assisted reproduction technology tool to boost critically
      small captive rhinoceros populations.

PMID- 17451806
TI  - Troponin C-based biosensors: a new family of genetically encoded indicators for
      in vivo calcium imaging in the nervous system.
AB  - Fluorescence imaging represents a powerful approach for the detection of
      intracellular Ca(2+) signals in vivo. With appropriate techniques, Ca(2+) signals
      can be recorded at many levels of complexity, ranging from large scale neuronal
      networks down to individual presynaptic boutons or postsynaptic spines. Here we
      review the applicability of genetically encoded Ca(2+) indicators for in vivo
      Ca(2+) imaging of neural function. We describe some of the recent progress in
      sensor design and evaluate the performance of the new family of Troponin C-based
      Ca(2+) indicators. Further, we analyze properties of Ca(2+) biosensors
      transgenically expressed in various experimental animal models and illustrate
      their use for measuring somatic and dendritic Ca(2+) signals in neurons of the
      mammalian brain.

PMID- 17451807
TI  - Characterization of a shrimp serine protease homolog, a binding protein of yellow
      head virus.
AB  - A serine protease homolog (SPH) cDNA namely SPH516 was identified via a yeast two
      hybrid screen between yellow head virus (YHV) proteins and hemocyte proteins of
      the black tiger shrimp Penaeus monodon. Initially, the C-terminal region of
      SPH516 (SPH516-C) was found to interact with a putative metal ion-binding domain
      (MIB) encoded by open-reading of frame ORF1b of the YHV genome. Subsequently, the
      full-length of SPH516 cDNA was obtained using 5' rapid amplification of cDNA ends
      (5' RACE) and it also bound specifically to the MIB domain only. Primers designed
      based on the SPH516 coding region amplified not only SPH516 but also an
      additional SPH named SPH509 from shrimp hemocytes using reverse transcriptase
      polymerase chain reaction (RT-PCR). These new SPHs had high homology to MasSPH
      previously reported from P. monodon. All shared the same domain features
      including a putative signal peptide, glycine-rich repeat motifs, a clip domain,
      an HDG triad and a trypsin-like serine protease domain. It is interesting that
      these sequences were phylogenetically closer to a prophenoloxidase-activating
      factor (PPAF) from blue crab than to another SPH from the black tiger shrimp
      reported to be involved in cell adhesion. Our SPH transcripts were highly
      expressed in hemocytes and gills and were found to be down-regulated after YHV
      infection. Immunohistochemistry using a polyclonal antibody raised against shrimp
      protein SPH516-C heterologously expressed in Escherichia coli revealed that
      SPH516 was present almost exclusively in the shrimp hemolymph.

PMID- 17451808
TI  - Differential induction of oxidative impairments in brain regions of male mice
      following subchronic consumption of Khesari dhal (Lathyrus sativus) and
      detoxified Khesari dhal.
AB  - Neurolathyrism is a neurodegenerative disease caused by the chronic consumption
      of Khesari dhal (Lathyrus sativus L). It is generally accepted that beta-N
      oxalylamino-l-alanine (b-ODAP), a non-protein amino acid present in the seeds is
      the primary causative agent. Based on in vitro studies with beta-ODAP, both
      excitotoxic and oxidative stress mechanisms have been speculated to be
      responsible for its neurotoxic effects. However, occurrence and the involvement
      of oxidative stress mechanisms in experimental animals following Khesari dhal
      consumption in vivo is less well understood. Accordingly in the present study, we
      have addressed primarily two questions: (i) whether dietary intake of Khesari
      dhal (KD) causes oxidative impairment in specific regions of brain, such as
      cortex and cerebellum and (ii) if there is any significant reduction in the
      oxidative damage induction following consumption of detoxified Khesari dhal
      (DKD). Adult male mice were fed either normal, KD or DKD incorporated diet (30%)
      for a period of 4 or 12 weeks. Biochemical markers of oxidative stress, such as
      lipid peroxidation (LPO), generation of reactive oxygen species (ROS), activity
      of antioxidant enzymes, protein carbonyls in brain regions (cortex, cerebellum)
      were determined. Mice fed KD diet showed enhanced LPO levels and ROS generation
      in brain, while the levels of LPO and ROS were unaltered in DKD mice. Interim
      sampling (4 weeks) also showed a similar trend though the degree of oxidative
      damage was lower. Depletion of reduced GSH, significant alterations in the
      activity of various antioxidant enzymes and enhanced protein carbonyls in brain
      in KD fed mice suggested that a state of oxidative stress exists in vivo.
      Interestingly, no significant induction of oxidative damage was evident in the
      brain of mice fed DKD. However, altered cholinergic function was discernible
      among both treatment groups. KD consumption resulted in a marked reduction of
      brain AChE activity at both sampling times (cortex, 38-43%; cerebellum, 22-41%),
      while DKD consumption resulted in less robust reduction (cortex, 11-17%;
      cerebellum, 11-13%). Taken together, these data suggest that dietary KD has the
      propensity to induce marked oxidative damage in brain of male mice, while DKD
      failed to induce any significant degree of oxidative impairments. Based on these
      results, it is hypothesized that oxidative stress mechanisms may wholly or in
      part contribute towards the development of neuro-degeneration associated with
      human consumption of L. sativus.

PMID- 17451809
TI  - Symptoms of neurasthenia following earthquake trauma: re-examination of a
      discarded syndrome.
AB  - The authors examined symptoms of neurasthenia in the context of trauma through a
      survey conducted 10 months post-earthquake, among a sample of earthquake
      survivors in rural Taiwan. An algorithm closely resembling neurasthenia as
      defined in ICD-10 was designed a priori. Three diagnostic groups were identified,
      including those with "pure" neurasthenia (n=27) who did not exhibit any Axis I
      disorder, those with an Axis I disorder but without neurasthenia (n=46) and
      controls who were without neurasthenia or an Axis I disorder (n=152). Those with
      neurasthenia were demographically similar to non-psychiatrically disordered
      controls and did not differ with respect to impact of trauma. Greater severity of
      intrusive and avoidant/numbing posttraumatic stress disorder (PTSD) symptoms and
      less resilience characterized neurasthenia relative to controls. Morbidity was
      similar for neurasthenia and Axis I disorders, except for the presence of less
      resilience in the neurasthenia group. Thus, "pure" neurasthenia appears to be
      independent from other psychopathology in a significant number of earthquake
      survivors, and was not closely related to the impact of earthquake trauma. The
      meaningful number of subjects meeting criteria for our algorithm of neurasthenia
      suggests that further study of this syndrome employing exact ICD-10 diagnostic
      criteria is warranted.

PMID- 17451810
TI  - Comparison of a standard psychiatric evaluation to rating scales and EEG in the
      differential diagnosis of attention-deficit/hyperactivity disorder.
AB  - The objective was to investigate the effectiveness of rating scales and
      electroencephalography (EEG) in detecting the presence of attention
      deficit/hyperactivity disorder (ADHD) within a diverse clinical sample. A
      standard psychiatric evaluation was used to assess 26 children/adolescents who
      presented to a clinic because a parent suspected the presence of ADHD. EEG data
      was collected in a blinded protocol, and rating scales were collected as well.
      Although all subjects had presented with ADHD-like symptoms, only 62% were
      diagnosed with ADHD, while the remaining 38% had other disorders or no diagnosis.
      Rating scales readily classified inattentive, impulsive, and/or hyperactive
      symptoms as being due to ADHD, regardless of the actual underlying disorder,
      leading to a sensitivity of 81% and a specificity of 22%. Previous studies have
      observed that there is an EEG marker that identifies ADHD vs. controls, and this
      marker was present in 15 out of 16 of the ADHD subjects (sensitivity=94%) and in
      none of the subjects with ADHD-like symptoms due to other disorders
      (specificity=100%). In the detection of ADHD in a diverse clinical sample, rating
      scales and EEG were both sensitive markers, whereas only EEG was specific. These
      results may have important implications to ADHD differential diagnosis.

PMID- 17451811
TI  - Serum amyloid A isoforms in serum and synovial fluid from spontaneously diseased
      dogs with joint diseases or other conditions.
AB  - Serum amyloid A (SAA) is a major acute phase protein in dogs. However, knowledge
      of qualitative properties of canine SAA and extent of its synthesis in
      extrahepatic tissues is limited. The aim of the study was to investigate
      expression of different SAA isoforms in serum and synovial fluid in samples
      obtained from dogs (n=16) suffering from different inflammatory or non
      inflammatory conditions, which were either related or unrelated to joints.
      Expression of SAA isoforms was visualized by denaturing isoelectric focusing and
      Western blotting. Serum amyloid A was present in serum from all dogs with
      systemic inflammatory activity, and up to four major isoforms with apparent
      isoelectric points between 6.1 and 7.9 were identified. In synovial fluid from
      inflamed joints one or more highly alkaline SAA isoforms (with apparent
      isoelectric points above 9.3) were identified, with data suggesting local
      production of these isoforms in the canine inflamed joint.

PMID- 17451812
TI  - Human gammadelta T lymphocytes strip and kill tumor cells simultaneously.
AB  - When human gammadelta lymphocytes bind to tumor cells for killing, they also
      strip their membrane for unknown reasons. Here we investigated this topic using
      the model of human gammadelta lymphocytes co-incubated with anaplastic large cell
      lymphomas, a group of tumors with cytolytic T or null lineage. By using flow
      cytometry and live cell imaging, we show that as soon as both cells were in
      contact, the TCR-mediated activation of gammadelta lymphocytes simultaneously
      triggered their secretion of lytic granules and stripping of lymphoma cell
      membranes, and both activities continued even after their cell death. However
      reciprocally in such conjugates, resistant lymphoma failed to strip gammadelta
      cells and to kill them by untargeted secretion of their own lytic granules. This
      indicated that secretion of lytic granules and target membrane stripping are
      associated in lytic cell conjugates, and that gammadelta T lymphocytes strip and
      kill their targets simultaneously.

PMID- 17451813
TI  - Self-tolerance, dendritic cell (DC)-mediated activation and tissue distribution
      of natural killer (NK) cells.
AB  - Natural killer (NK) cells are lymphocytes of the innate immune system that exert
      a potent function against infected and tumor cells. Although NK cells were
      originally defined by their capacity to lyse target cells and produce interferon
      (IFN)-gamma without prior activation, more recent studies found that NK cells
      display also a potent regulatory function. Following engagement of surface
      receptors by other cells or signalling by soluble molecules, NK cells release
      cytokines able to influence the outcome of an immune response. Since their
      discovery in the 1970s, the biology of NK cells has been deeply investigated;
      nevertheless some aspects of their maturation process, activation mechanisms, and
      tissue distribution remain still obscure. These review will focus on three major
      issues regarding NK cell regulation. In particular we aim to discuss: (i) how NK
      cells become tolerant to self-tissues during their maturation; (ii) how NK cells
      become activated, with a particular attention to dendritic cell (DC)-mediated
      mechanisms of NK cell priming; (iii) where NK cells play their functions and how
      NK cell tissue distribution can favour their capacity to skew T cell responses.

PMID- 17451814
TI  - Antigen specificity of clonally expanded and receptor edited cerebrospinal fluid
      B cells from patients with relapsing remitting MS.
AB  - We re-engineered the immunoglobulin rearrangements from clonally expanded CSF B
      cells of three Multiple Sclerosis patients as Fab fragments, and used three
      methods to test for their antigen (Ag) specificity. Nine out of ten Fab fragments
      were reactive to Myelin Basic Protein (MBP). The one Fab that did not react to
      MBP was a product of receptor editing. Two of the nine MBP reactive Fabs were
      also reactive to GFAP and CNPase, indicating that these clones were polyreactive.
      Targeting the mechanisms that allow these self-reactive B cells to reside in the
      CSF of MS patients may prove to be a potent immunotherapeutic strategy.

PMID- 17451815
TI  - Microarray-based molecular detection of foot-and-mouth disease, vesicular
      stomatitis and swine vesicular disease viruses, using padlock probes.
AB  - The World Organization for Animal Health (Office International des Epizooties,
      OIE) includes the diseases caused by foot-and-mouth disease virus (FMDV), swine
      vesicular disease virus (SVDV), and vesicular stomatitis virus (VSV), as
      "Diseases Notifiable to the OIE". Foot-and-mouth disease (FMD) outbreaks have
      severe economical as well as social effects and cannot be differentiated from the
      diseases caused by the other two viruses on the basis of clinical symptoms.
      Efficient laboratory techniques are therefore required for detection and
      identification of the viruses causing similar vesicular symptoms in swine. A
      rapid method is described using padlock probes and microarrays to detect
      simultaneously and differentiate the three viruses in a single reaction, as well
      as providing serotype information in cases of VSV infection. The padlock
      probe/microarray assay detected successfully and identified 39 cDNA samples of
      different origin representing the three viruses. The results were in complete
      agreement with identities and serotypes determined previously. This novel virus
      detection method is discussed in terms of usefulness and further development.

PMID- 17451816
TI  - Characterization and diagnostic use of a recombinant single-chain antibody
      specific for the gp116 envelop glycoprotein of Yellow head virus.
AB  - Yellow head virus (YHV) is an invertebrate nidovirus that can cause mass
      mortality of the cultured Penaeus monodon shrimp. A single-chain variable
      fragment (scFv) antibody directed against the gp116 envelop glycoprotein of YHV
      was constructed from hybridomas. Variable heavy (V(H)) and light (V(L)) chain
      genes were amplified from cDNA using antibody-specific primers, linked to
      generate a full-length gene via a standard peptide linker, ligated into the
      pET28a expression vector and transformed into E. coli. The expressed insoluble
      scFv antibody was solubilized, purified using immobilized metal affinity
      chromatography and rapid refolded; final yield 1-1.5 mg/l. Solid-phase non
      competitive enzyme-linked immunosorbent assay (non-competitive ELISA) determined
      the affinity constant (K(A)) to be 3.34+/-0.38 x 10(8)l/mol. The sensitivity and
      specificity of scFv antibody was demonstrated by ELISA, dot blot and Western blot
      analysis. The detection limit determined by dot blot and indirect ELISA was 9 ng
      and 45 ng of purified YHV, respectively. Dot-blot assays revealed that the scFv
      antibody could detect YHV-infected shrimp at 24h post-infection and did not cross
      react with White spot syndrome virus (WSSV) and Taura syndrome virus (TSV)
      proteins. The scFv antibody therefore might find application in rapid, simple and
      sensitive diagnostic tests to detect YHV in farmed shrimp.

PMID- 17451818
TI  - Repeated pre-exposure to morphine into the ventral pallidum enhances morphine
      induced place preference: involvement of dopaminergic and opioidergic mechanisms.
AB  - In the present study, the effect of repeated administration of morphine into the
      ventral pallidum (intra-VP) on the conditioned place preference (CPP) induced by
      systemic morphine injection was investigated in male Wistar rats. Subcutaneous
      (s.c.) administration of morphine (2.5, 5 and 7.5mg/kg), during conditioning,
      induced conditioned place preference (CPP). The maximum response was obtained
      with 5mg/kg of morphine. Lower dose of morphine (0.5mg/kg) did not induce CPP,
      but in the animals which had previously, received 3 days intra-VP repeated
      injections of morphine (3 or 5microg/rat) followed by 5 days free of the drug,
      elicited a significant CPP. Moreover, 3 days intraperitoneal (i.p.) pretreatment
      with different doses of naloxone (0.5, 1 and 2mg/kg), SCH 23390 (0.012, 0.025 and
      0.05mg/kg) or sulpiride (6.2, 12.5 and 25mg/kg) in combination with repeated
      injections of morphine (5microg/rat), blocked the opioid response on the
      acquisition of morphine (0.5mg/kg) CPP. On the other hand, our results showed
      that 3 days single repeated administration of different doses of naloxone (0.5, 1
      or 2mg/kg, i.p.), SCH 23390 but not sulpiride followed by 5 days free of the
      drug, significantly decreased the acquisition of morphine (0.5mg/kg) CPP and also
      induced place aversion. Furthermore, the drugs' injections had no effect on
      locomotor activity on the testing phase of CPP. It is concluded that repeated
      intra-VP injections of morphine induces behavioral sensitization, which may be
      due to the opioidrgic and/or dopaminergic mechanism(s).

PMID- 17451817
TI  - Enhanced protective efficacy of H5 subtype avian influenza DNA vaccine with codon
      optimized HA gene in a pCAGGS plasmid vector.
AB  - H5N1 influenza viruses have caused significant disease and deaths in various
      parts of the world in several species, including humans. Vaccination combined
      with culling can provide an attractive method for outbreak containment. Using
      synthesized oligos and overlapping extension PCR techniques, we constructed an H5
      HA gene, optiHA, containing chicken biased codons based on the HA amino acid
      sequence of the highly pathogenic H5N1 virus A/goose/Guangdong/1/96 (GS/GD/96).
      The optiHA and wild-type HA genes were inserted into plasmids pCI or pCAGGS, and
      designated as pCIoptiHA, pCAGGoptiHA, pCIHA and pCAGGHA, respectively. To
      evaluate vaccine efficacy, groups of 3-week-old specific pathogen free (SPF)
      chickens were intramuscularly injected with the four plasmids. Sera were
      collected on a weekly basis post-vaccination (p.v.) for hemagglutination
      inhibition (HI) assays and neutralization (NT) antibody detection. All chickens
      receiving pCAGGoptiHA and pCAGGHA developed high levels of HI and NT antibodies
      at 3 weeks p.v., and were completely protected from lethal H5 virus challenge,
      while only partial protection was induced by inoculation with the other two
      plasmids. A second experiment was conducted to evaluate if a lower dose of the
      pCAGGoptiHA vaccine could be effective, results indicated that two doses of 10
      microg of pCAGGoptiHA could induce complete protection in chickens against H5
      lethal virus challenge. Based on our results, we conclude that construction
      optimization could dramatically increase the H5 HA gene DNA vaccine efficacy in
      chickens, and therefore, greatly decrease the dose necessary for inducing
      complete protection in chickens.

PMID- 17451819
TI  - Enhancing effects of lithium on memory are not by-products of learning or
      attentional deficits.
AB  - We recently reported that chronic lithium (LiCl), at therapeutic plasma levels,
      enhanced spatial working memory and retention of an aversive contingency. Here we
      examine the possibility that these effects be secondary to LiCl effects on the
      ability to ignore irrelevant stimuli or on fear conditioning. In Experiment 1,
      rats subjected to >30 daily intraperitoneal injections of LiCl (2mmol/kg) or
      saline underwent conditioned emotional response training (CER: 2 CS pairings with
      1-s, 1-mA shock) after 40 pre-exposures either to the CS (latent inhibition
      LiCl/latent inhibition-saline, n=8) or to another stimulus (control-LiCl/control
      saline, n=8). In Experiment 2, eight LiCl and eight saline animals were trained
      in on-the-baseline (VI-60s) CER (1-s, 0.15-mA shock in CS-signalled periods) in
      the Skinner box. In Experiment 1, LiCl animals showed normal latent inhibition.
      In both experiments, their fear conditioning was unimpaired. Therefore, the
      previously reported memory improvement under chronic lithium cannot be attributed
      to changes in the ability to ignore irrelevant stimuli or in fear conditioning.

PMID- 17451820
TI  - Hypofunctional glutamatergic neurotransmission in the prefrontal cortex is
      involved in the emotional deficit induced by repeated treatment with
      phencyclidine in mice: implications for abnormalities of glutamate release and
      NMDA-CaMKII signaling.
AB  - In the present study, we investigated the involvement of prefrontal glutamatergic
      neurotransmission in the enhancement of immobility (emotional deficit) in a
      forced swimming test in mice treated with phencyclidine (PCP: 10mg/kg/day for 14
      days) repeatedly, which is regarded as an animal model for negative symptoms. A
      decrease in spontaneous extracellular glutamate release and increase in levels of
      the glutamate transporter GLAST, were observed in the prefrontal cortex (PFC) of
      PCP-treated mice, compared to saline-treated mice. NMDA receptor subunit 1 (NR1)
      and Ca(2+)/calmoduline kinase II (CaMKII) were markedly activated in the PFC of
      saline-treated mice, but not PCP-treated mice, immediately after the forced
      swimming test. The facilitation of the function of NMDA receptors by d
      cycloserine (30mg/kg i.p.), an NMDA receptor glycine-site partial agonist,
      reversed the enhancement of immobility in the forced swimming test and impairment
      of CaMKII activation in the PCP-treated mice. Microinjection of dl-threo-beta
      benzyloxyaspartate (10nmol/site/bilaterally), a potent blocker of glutamate
      transporters, into the PFC of PCP-treated mice also had an attenuating effect. In
      addition, activation of glial cells and a decrease of neuronal cell size were
      observed in the PFC of PCP-treated mice. These results suggest that repeated PCP
      treatment disrupts pre- and post-synaptic glutamatergic neurotransmission and
      induces morphological changes in the PFC and that such changes cause the
      emotional deficits exhibited in PCP-treated mice.

PMID- 17451821
TI  - Molecular and histological evaluation of tributyltin toxicity on spermatogenesis
      in a marine fish, the mummichog (Fundulus heteroclitus).
AB  - There is still concern about the effects of organotin compounds (OTs) on marine
      organisms, and especially on their reproductive systems. We investigated the
      toxicity of tributyltin oxide (TBTO) on spermatogenesis in a marine fish,
      mummichog, Fundulus heteroclitus. TBTO exposure caused serious histological
      damage to the testis, including reduction in counts of spermatids and spermatozoa
      and malformation of somatic cells around the seminal duct. Analysis of the
      incorporation of bromodeoxyuridine into spermatogenic cells revealed inhibition
      of the proliferation of germ cells. To find a biomarker for evaluation of the
      effects of TBTO on fish spermatogenesis, we cloned genes downregulated by TBTO
      exposure in the mummichog testis, and identified mummichog creatine kinase (mCK).
      The cDNA sequence of mCK contained an open reading frame encoding 387 amino acid
      residues (M(r)=43,344). The derived amino acid sequence of mCK was very similar
      to that of the testicular-type CK of the rainbow trout, Oncorhynchus mykiss.
      Furthermore, Northern blot analysis revealed that mCK was produced specifically
      in the testis. We therefore identified mCK in the mummichog as a testicular-type
      CK. Real-time PCR revealed that exposure of the fish to TBTO significantly
      reduced mCK expression in the testis. To some extent, this reduction was
      coincident with that of bromodeoxyuridine incorporation into spermatogenic cells.
      The mCK gene can therefore be used as a biomarker for evaluating the effects of
      TBTO on fish spermatogenesis. In addition, levels of expression of the mCK gene
      in control fish were well correlated with increments in the gonad somatic index
      (GSI) below 4%. Individuals that were thought to have testicular damage caused by
      TBTO could be discriminated from those considered normal. The results suggest
      that TBTO is involved in the suppression of fish spermatogenesis and that
      analysis of both GSI values and mCK gene expression is useful for evaluating the
      levels of xenobiotic pollution in coastal areas.

PMID- 17451822
TI  - Pyrimethamine-resistant dihydrofolate reductase enzymes of Plasmodium falciparum
      are not enzymatically compromised in vitro.
AB  - Plasmodium falciparum, the protozoan that causes the most lethal form of human
      malaria, has been controlled principally by two safe, affordable drugs,
      chloroquine and sulfadoxine-pyrimethamine (SP). Studies in the laboratory and in
      the field have demonstrated that resistance to SP depends on non-synonymous point
      mutations in the dihydrofolate reductase (DHFR), and dihydropteroate synthase
      (DHPS) coding regions. Parasites that carry dhfr genes with 3 or 4 point
      mutations (51I/59R/108N triple mutation or 51I/59R/108N/164L quadruple mutation)
      are resistant to pyrimethamine in vitro and patients infected with these
      parasites respond poorly to SP treatment. The wide spread of these pyrimethamine
      resistant alleles demonstrates the increased fitness over drug-sensitive alleles
      in the presence of the drug. However, it is not clear whether these alleles might
      reduce the fitness of parasites in the absence of drug pressure. As a first step,
      we compared the kinetic properties of the wild type, and three mutant alleles to
      determine whether the native DHFR-thymidylate synthase form of the mutant
      proteins showed compromised activity in vitro. The mutant enzymes had K(m) values
      for their substrate, dihydrofolate that were significantly lower than the wild
      type, k(cat) values in the same range as the wild type enzyme, and k(cat)/K(m)
      values higher than wild type. In contrast, the K(m) values for the NADPH cofactor
      were higher than wild type for the mutant enzymes. These observations suggest
      that the fitness of these parasites may not be compromised relative to those that
      carry the wild type allele, even without sustained SP drug pressure.

PMID- 17451823
TI  - Proteomic analysis of adult S. mansoni gut contents.

PMID- 17451824
TI  - Nitric oxide attenuates hydrogen peroxide-induced barrier disruption and protein
      tyrosine phosphorylation in monolayers of intestinal epithelial cell.
AB  - The intestinal epithelium provides a barrier to the transport of harmful luminal
      molecules into the systemic circulation. A dysfunctional epithelial barrier is
      closely associated with the pathogenesis of a variety of intestinal and systemic
      disorders. We investigated here the effects of nitric oxide (NO) and hydrogen
      peroxide (H(2)O(2)) on the barrier function of a human intestinal epithelial cell
      line, Caco-2. When treated with H(2)O(2), Caco-2 cell monolayers grown on
      permeable supports exhibited several remarkable features of barrier dysfunction
      as follows: a decrease in transepithelial electrical resistance, an increase in
      paracellular permeability to dextran, and a disruption of the intercellular
      junctional localization of the scaffolding protein ZO-1. In addition, an
      induction of tyrosine phosphorylation of numerous cellular proteins including ZO
      1, E-cadherin, and beta-catenin, components of tight and adherens junctions, was
      observed. On the other hand, combined treatment of Caco-2 monolayers with
      H(2)O(2) and an NO donor (NOC5 or NOC12) relieved the damage to the barrier
      function and suppressed the protein tyrosine phosphorylation induced by H(2)O(2)
      alone. These results suggest that NO protects the barrier function of intestinal
      epithelia from oxidative stress by modulating some intracellular signaling
      pathways of protein tyrosine phosphorylation in epithelial cells.

PMID- 17451825
TI  - Compositional analysis of angioscopic yellow plaques with intravascular
      ultrasound radiofrequency data.
AB  - BACKGROUND: To identify subclinical high-risk plaques is potentially important
      because those vulnerable plaques may have a greater likelihood of rupture and
      subsequent thrombosis. The aim of this study is to reveal the histology of
      angioscopic yellow plaques known as vulnerable plaques by intravascular
      ultrasound radiofrequency data analysis. METHODS: Thirty-one coronary plaques in
      21 patients, which were non-culprit, de novo, angiographically non-obstructive
      (<50%) lesions, were analyzed with Virtual Histology - intravascular ultrasound
      (VH-IVUS) and coronary angioscopy. These plaques were prospectively divided into
      4 groups (Grade 0 to 3) by the yellow color intensity and we compared plaque
      morphology, echogenicity and composition among their groups. RESULTS: Morphology
      and echogenicity evaluated by standard gray-scale IVUS were not significantly
      different among those groups. On analyzing plaque composition by VH-IVUS, mean
      percentage of necrotic core was significantly larger in yellow plaque (Grade 2
      and 3) than white plaque (Grade 0). CONCLUSIONS: Angioscopic yellow plaque
      included a larger amount of necrotic core analyzed by VH-IVUS than white plaque.

PMID- 17451826
TI  - Evaluation of peanut genotypes for in vitro plant regeneration using thidiazuron.
AB  - A major limitation with the available protocols for in vitro regeneration of
      peanut (Arachis hypogaea L.) is their narrow application to very few select
      genotypes. Here, we report a protocol that can be applied across a broad spectrum
      of peanut market types, explant types and geographic regions using thidiazuron
      (TDZ). The effect of the timing of TDZ application to the culturing of both
      zygotic embryos and subsequent plantlet explants on MS medium is also reported.
      An extended use of TDZ and at a higher concentration (30 m/l) resulted in the
      greatest explant shoot average (approximately 13). However, a limited application
      of TDZ (10 d) was sufficient to induce shoot formation in peanut. Hypocotyl was
      the best explant type that induced the greatest shoot average (15) across market
      types followed by lamina (7.4). Spanish and Valencia were the most efficient
      market groups that induced shoots across explant types, consistently.

PMID- 17451827
TI  - SARS coronavirus and innate immunity.
AB  - The emergence of the highly pathogenic SARS coronavirus (SARS-CoV) has reignited
      interest in coronavirus biology and pathogenesis. An emerging theme in
      coronavirus pathogenesis is that the interaction between specific viral genes and
      the host immune system, specifically the innate immune system, functions as a key
      determinant in regulating virulence and disease outcomes. Using SARS-CoV as a
      model, we will review the current knowledge of the interplay between coronavirus
      infection and the host innate immune system in vivo, and then discuss the
      mechanisms by which specific gene products antagonize the host innate immune
      response in cell culture models. Our data suggests that the SARS-CoV uses
      specific strategies to evade and antagonize the sensing and signaling arms of the
      interferon pathway. We summarize by identifying future points of consideration
      that will contribute greatly to our understanding of the molecular mechanisms
      governing coronavirus pathogenesis and virulence, and the development of severe
      disease in humans and animals.

PMID- 17451828
TI  - Emerging epidemic dog rabies in coastal South Africa: a molecular epidemiological
      analysis.
AB  - Towards understanding the molecular epidemiology of a severe dog rabies epidemic
      in the KwaZulu Natal province of South Africa, we analyzed a variable 592
      nucleotide genome sequence domain of 170 rabies viruses from KwaZulu Natal and
      surrounding regions. Viruses from the KwaZulu Natal and Eastern Cape provinces
      belonged to a unique lineage, circulating as two independent and expanding
      epidemiological cycles. The first presented as closely related dog cycles along
      the eastern coastal regions of the two provinces, while the second, in northern
      KwaZulu Natal, has entered into at least one wildlife reservoir, the black backed
      jackal. We underline the success and opportunism of rabies in southern Africa, in
      a likely reflection of the emergence and radiation of rabies in new host species
      and locales throughout the larger continent as a whole.

PMID- 17451829
TI  - SARS-CoV replication and pathogenesis in an in vitro model of the human
      conducting airway epithelium.
AB  - SARS coronavirus (SARS-CoV) emerged in 2002 as an important cause of severe lower
      respiratory tract infection in humans and in vitro models of the lung are needed
      to elucidate cellular targets and the consequences of viral infection. The severe
      and sudden onset of symptoms, resulting in an atypical pneumonia with dry cough
      and persistent high fever in cases of severe acute respiratory virus brought to
      light the importance of coronaviruses as potentially lethal human pathogens and
      the identification of several zoonotic reservoirs has made the reemergence of new
      strains and future epidemics all the more possible. In this chapter, we describe
      the pathology of SARS-CoV infection in humans and explore the use of two models
      of the human conducting airway to develop a better understanding of the
      replication and pathogenesis of SARS-CoV in relevant in vitro systems. The first
      culture model is a human bronchial epithelial cell line Calu-3 that can be
      inoculated by viruses either as a non-polarized monolayer of cells or polarized
      cells with tight junctions and microvilli. The second model system, derived from
      primary cells isolated from human airway epithelium and grown on Transwells, form
      a pseudostratified mucociliary epithelium that recapitulates the morphological
      and physiological features of the human conducting airway in vivo. Experimental
      results using these lung epithelial cell models demonstrate that in contrast to
      the pathology reported in late stage cases SARS-CoV replicates to high titers in
      epithelial cells of the conducting airway. The SARS-CoV receptor, human
      angiotensin 1 converting enzyme 2 (hACE2), was detected exclusively on the apical
      surface of cells in polarized Calu-3 cells and human airway epithelial cultures
      (HAE), indicating that hACE2 was accessible by SARS-CoV after lumenal airway
      delivery. Furthermore, in HAE, hACE2 was exclusively localized to ciliated airway
      epithelial cells. In support of the hACE2 localization data, the most productive
      route of inoculation and progeny virion egress in both polarized Calu-3 and
      ciliated cells of HAE was the apical surface suggesting mechanisms to release
      large quantities of virus into the lumen of the human lung. Preincubation of the
      apical surface of cultures with antisera directed against hACE2 reduced viral
      titers by two logs while antisera against DC-SIGN/DC-SIGNR did not reduce viral
      replication levels suggesting that hACE2 is the primary receptor for entry of
      SARS-CoV into the ciliated cells of HAE cultures. To assess infectivity in
      ciliated airway cultures derived from susceptible animal species we generated a
      recombinant SARS-CoV by deletion of open reading frame 7a/7b (ORF 7a/7b) and
      insertion of the green fluorescent protein (GFP) resulting in SARS-CoV GFP. SARS
      CoV GFP replicated to similar titers as wild type viruses in Vero E6, MA104, and
      CaCo2 cells. In addition, SARS-CoV replication in airway epithelial cultures
      generated from Golden Syrian hamster tracheas reached similar titers to the human
      cultures by 72 h post-infection. Efficient SARS-CoV infection of ciliated cell
      types in HAE provides a useful in vitro model of human lung origin to study
      characteristics of SARS-CoV replication and pathogenesis.

PMID- 17451830
TI  - A review of studies on animal reservoirs of the SARS coronavirus.
AB  - In this review, we summarize the researches on animal reservoirs of the SARS
      coronavirus (SARS-CoV). Masked palm civets were suspected as the origin of the
      SARS outbreak in 2003 and was confirmed as the direct origin of SARS cases with
      mild symptom in 2004. Sequence analysis of the SARS-CoV-like virus in masked palm
      civets indicated that they were highly homologous to human SARS-CoV with nt
      identity over 99.6%, indicating the virus has not been circulating in the
      population of masked palm civets for a very long time. Alignment of 10 complete
      viral genome sequences from masked palm civets with those of human SARS-CoVs
      revealed 26 conserved single-nucleotide variations (SNVs) in the viruses from
      masked palm civets. These conserved SNVs were gradually lost from the genomes of
      viruses isolated from the early phase to late phase human patients of the 2003
      SARS epidemic. In 2005, horseshoe bats were identified as the natural reservoir
      of a group of coronaviruses that are distantly related to SARS-CoV. The genome
      sequences of bat SARS-like coronavirus had about 88-92% nt identity with that of
      the SARS-CoV. The prevalence of antibodies and viral RNA in different bat species
      and the characteristics of the bat SARS-like coronavirus were elucidated. Apart
      from masked palm civets and bats, 29 other animal species had been tested for the
      SARS-CoV, and the results are summarized in this paper.

PMID- 17451831
TI  - Rabbits immunised with recombinant BCG expressing the cottontail rabbit
      papillomavirus (CRPV) L2E7E2 genes induces regression of established papillomas.
AB  - We previously demonstrated in a cottontail rabbit papillomavirus (CRPV) challenge
      model that recombinant Bacille Calmette-Guerin (rBCG) could potentially be used
      as a prophylactic vaccine vehicle to deliver papillomavirus proteins. In this
      study we investigated whether regression of CRPV-induced papillomas could be
      achieved following immunisation of out-bred New Zealand White rabbits with rBCG
      expressing CRPVL2, CRPVE2, CRPVE7 or CRPVL2E7E2 proteins. Rabbits immunised with
      rBCG/CRPVL2E7E2 had papillomas that were largely suppressed and were
      significantly smaller compared to the rBCG negative control group (P</=0.01). In
      addition, four of the six rabbits immunised with rBCG/CRPVL2E7E2 had papillomas
      that completely regressed 1.5 weeks post third immunisation. Rabbits immunised
      with rBCG/CRPVL2, rBCG/CRPVE7, or rBCG/CRPVE2 had papillomas that were
      significantly smaller than the negative control rabbits (P</=0.05). The findings
      in this study suggest that BCG could probably be used as a vaccine delivery
      vehicle for human papillomavirus proteins as a possible therapeutic vaccine.

PMID- 17451832
TI  - Effect of interferon-lambda on replication of hepatitis B virus in human hepatoma
      cells.
AB  - The antiviral activity of interferon-lambda (IFN-lambda) against several viruses
      has been reported, but it has not been investigated whether human IFN-lambda can
      affect replication of the hepatitis B virus (HBV) in human hepatocyte-derived
      cells. We found that replication of HBV in a human hepatoma cell line was reduced
      by approximately 30% following treatment with a high concentration of IFN-lambda.
      Furthermore, we showed that replication of HBV in another human hepatoma cell
      line was not suppressed by IFN-lambda. However, these cell lines showed a similar
      level of transcription for the heterodimeric IFN-lambda receptor and the IFN
      lambda-induced antiviral proteins. Our results suggest that the antiviral
      activity of IFN-lambda against HBV may be limited in human cells.

PMID- 17451833
TI  - Synthesis, biodistribution and excretion of radiolabeled poly(2-alkyl-2
      oxazoline)s.
AB  - Here we report on the preparation of well defined water-soluble poly(2-methyl-2
      oxazoline) and poly(2-ethyl-2-oxazoline) terminally equipped with a chelator
      (N,N',N'',N'''-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA)) for
      radionuclide labeling. The tissue distribution and excretion of (111)In-labeled
      poly(2-alkyl-2-oxazoline)s were studied in mice. We found that the hydrophilic
      polymers do not accumulate in tissues and are rapidly cleared from the blood
      pool, predominantly by glomerular filtration in the kidneys. In contrast only a
      small fraction is excreted via the hepatobiliary tract. Only minimal amounts of
      poly(2-alkyl-2-oxazoline)s are taken up by the reticuloendothelial system (RES).
      Scintigraphic studies revealed the feasibility of in vivo imaging of (111)In
      labeled poly(2-oxazoline)s. Since additional functionalities for targeting can
      readily be introduced into poly(2-oxazoline)s via functional monomer units, these
      compounds fulfill fundamental requirements for an application as carrier
      molecules in radionuclide therapy.

PMID- 17451834
TI  - [Quality of life outcome of elderly patients after treatment in intensive care
      unit].

PMID- 17451835
TI  - Both Pdx-1 and NeuroD1 genes are requisite for the maintenance of insulin gene
      expression in ES-derived differentiated cells.
AB  - Embryonic stem (ES) cells can differentiate into many cell types. Recent reports
      have shown that ES cells can differentiate into insulin-producing cells. We have
      established an ES cell line in which exogenous Pdx-1 expression was precisely
      regulated by the Tet-off system integrated into the ROSA26 locus and succeeded to
      produce insulin-producing cells. The Pdx-1 expressing final differentiated
      insulin-positive cells can be maintained for more than 2 months. However, in
      spite of their induced expression of Pdx-1, the repeated passages of cells lost
      their capacity to express insulin and NeuroD1 gene. Forced expression of NeuroD1
      gene by adenoviral vector in these cells restored the expression of insulin.
      These results suggested that maintenance of the property of insulin-producing
      cells derived from ES cells could be achieved by synergistic expression of Pdx-1
      and NeuroD1.

PMID- 17451836
TI  - Genetic factors related to mitochondrial function and risk of diabetes mellitus.
AB  - Mitochondria are the intracellular organelles responsible for the generation of
      ATP by the process of oxidative phosphorylation (OXPHOS) and have their own DNA
      containing genes for 13 subunits of OXPHOS and 2 rRNAs and 22 tRNAs for their
      protein synthesis machinery. Since mitochondrial DNA (mtDNA) has limited coding
      capacity, nuclear genes make a major contribution to mitochondrial architecture,
      metabolic systems and biogenesis. Nowadays, there is a growing body of evidence
      that the mitochondrial dysfunction plays a crucial role in the pathogenesis of
      type 2 diabetes. In this review, we showed that mtDNA copy number in peripheral
      blood cells is associated with various pathophysiological characteristics of type
      2 diabetes such as insulin resistance and insulin secretory defect. In addition,
      peripheral blood mtDNA copy number is a risk factor for the development of type 2
      diabetes. Common polymorphisms in mtDNA and nuclear genes regulating
      mitochondrial function might be associated with type 2 diabetes. Elucidation of
      genetic factors regulating mitochondrial function would be of help to understand
      how mitochondrial dysfunction is linked to the pathogenesis of type 2 diabetes.

PMID- 17451838
TI  - Computational models of myocardial endomysial collagen arrangement.
AB  - Collagen extracellular matrix is one of the factors related to high passive
      stiffness of cardiac muscle. However, the architecture and the mechanical aspects
      of the cardiac collagen matrix are not completely known. In particular,
      endomysial collagen contribution to the passive mechanics of cardiac muscle as
      well as its micro anatomical arrangement is still a matter of debate. In order to
      investigate mechanical and structural properties of endomysial collagen, we
      consider two alternative computational models of some specific aspects of the
      cardiac muscle. These two models represent two different views of endomysial
      collagen distribution: (1) the traditional view and (2) a new view suggested by
      the data obtained from scanning electron microscopy (SEM) in NaOH macerated
      samples (a method for isolating collagen from the other tissue). We model the
      myocardial tissue as a net of spring elements representing the cardiomyocytes
      together with the endomysial collagen distribution. Each element is a viscous
      elastic spring, characterized by an elastic and a viscous constant. We connect
      these springs to imitate the interconnections between collagen fibers. Then we
      apply to the net of springs some external forces of suitable magnitude and
      direction, obtaining an extension of the net itself. In our setting, the ratio
      forces magnitude /net extension is intended to model the stress /strain ratio of
      a microscopical portion of the myocardial tissue. To solve the problem of the
      correct identification of the values of the different parameters involved, we use
      an artificial neural network approach. In particular, we use this technique to
      learn, given a distribution of external forces, the elastic constants of the
      springs needed to obtain a desired extension as an equilibrium position. Our
      experimental findings show that, in the model of collagen distribution structured
      according to the new view, a given stress /strain ratio (of the net of springs,
      in the sense specified above) is obtained with much smaller (w.r.t. the other
      model, corresponding to the traditional view) elasticity constants of the
      springs. This seems to indicate that by an appropriate structure, a given
      stiffness of the myocardial tissue can be obtained with endomysial collagen
      fibers of much smaller size.

PMID- 17451837
TI  - Succinate is a paracrine signal for liver damage.
AB  - BACKGROUND/AIMS: A G-protein-coupled succinate receptor has recently been
      identified in several tissues, including the liver. The objectives of this work
      were to determine the hepatic cell types that express this receptor and to
      determine its physiological role. METHODS: Expression and distribution of the
      succinate receptor was determined by RT-PCR and confocal immunofluorescence.
      Biochemical assays were used to measure succinate and cAMP. Cytosolic Ca2+ was
      monitored in single cells by time-lapse imaging. Western blot was used to study
      the effect of succinate on activation of hepatic stellate cells. RESULTS: The
      succinate receptor was expressed in quiescent hepatic stellate cells, and
      expression decreased with activation. Ischemia induced release of succinate in
      isolated perfused livers. In contrast to what is observed in cell expression
      systems, succinate did not inhibit cAMP production or increase cytosolic Ca2+ in
      primary hepatic stellate cells. However, succinate accelerated stellate cell
      activation. CONCLUSIONS: Hepatic stellate cells express the succinate receptor.
      Succinate may behave as a paracrine signal by which ischemic hepatocytes trigger
      stellate cell activation.

PMID- 17451839
TI  - A software tool for interactive generation, representation, and systematical
      storage of transfer functions for 3D medical images.
AB  - As being a tool that assigns optical parameters, i.e. color, transparency, used
      in interactive visualization, transfer functions have very important effects on
      the quality of volume rendered medical images. However, finding accurate transfer
      functions is a very difficult, tedious, and time consuming task because of the
      variety of all possibilities. By addressing this problem, a software module,
      which can be easily plugged into any visualization program, is developed based on
      the specific expectations of medical experts. Its design includes both a new user
      interface to ease the interactive generation of the volume rendered medical
      images and a volumetric histogram based method for initial generation of transfer
      functions. In addition, a novel file system has been implemented to represent 3D
      medical images using transfer functions based on the DICOM standard. For
      evaluation of the system by various medical experts, the software is installed
      into a DICOM viewer. Based on the feedback obtained from the medical experts,
      several improvements are made, especially to increase the flexibility of the
      program. The final version of the implemented system shortens the transfer
      function design process and is applicable to various application areas.

PMID- 17451840
TI  - Exogenous siRNA delivery using peptide transduction domains/cell penetrating
      peptides.
AB  - The cellular membrane constitutes an effective barrier that offers protection for
      the complex, yet highly ordered, intracellular environment that defines the cell.
      Passage of molecules across this barrier is highly regulated and highly
      restricted, with molecular size being the most significant criteria. Over the
      last 15 years, a class of small cationic peptides has been discovered that can
      defy the rules of membrane passage and can gain access to the intracellular
      environment. Importantly, cellular entrance is also permitted for covalently
      coupled cargo. The cationic nature of these peptides is crucial for their ability
      to bind and traverse the anionic cellular membrane. Cell penetrating peptides
      (CPPs) have been used for the delivery of a wide range of macromolecules
      including peptides, proteins and antisense oligonucleotides. With the recent
      advancement and understanding of RNA interference (RNAi), CPPs offer an
      attractive means for the cellular uptake of double-stranded siRNAs to induce a
      RNAi response. This review focuses on the potential use of CPPs to deliver siRNA
      into cells and the implications of this technology for both gene function
      determination and therapeutic potential.

PMID- 17451841
TI  - Skeletal metastases in non-small cell lung cancer: a retrospective study.
AB  - BACKGROUND: The skeleton is one of the most common sites of metastasis in
      patients with advanced cancer. Bone metastases often cause SREs (skeletal-related
      events). Despite advances in the treatment of primary lung cancer, SREs still
      affect many patients. Therefore, we planned a retrospective study to investigate
      the clinical impact of SREs, and to compare differences in the therapeutic
      outcome between patients with and without skeletal metastases or SRE. PATIENTS
      AND METHODS: We retrospectively investigated the charts of all 259 patients with
      non-small cell lung cancer (NSCLC) who consulted the Department of Medical
      Oncology at Kinki University School of Medicine between February 2002 and January
      2005. We assessed their TNM stage, presence of skeletal metastases (on bone
      scintigraphy, MRI, and plain X-ray films), and outcome parameters such as SREs,
      analgesic use, and survival. RESULTS: A total of 70 patients (30.4%) were found
      to have skeletal metastases during their clinical course and 35 patients (50%)
      out of all 70 patients had SREs. Among 135 stage IV patients, a total of 56 (41%)
      had skeletal metastases, and 25 of these 56 patients (45%) had SREs. The most
      common SREs were the need for radiotherapy (34.3%) and hypercalcemia (20%).
      Patients with SREs tended to have worse survival, while no significant difference
      of survival was observed between patients with and without skeletal metastases.
      CONCLUSION: It seems to be important to prevent SREs during the treatment of
      NSCLC, so further studies evaluating bisphosphonates in combination with
      chemotherapy are warranted.

PMID- 17451842
TI  - National survey of non-small cell lung cancer in the United States: epidemiology,
      pathology and patterns of care.
AB  - PURPOSE: To determine the epidemiology, pathology and patterns of care for
      patients with non-small cell lung cancer (NSCLC) in the United States. METHODS:
      In 2001 the National Cancer Data Base, under direction of the American College of
      Surgeons, conducted a patient care evaluation study in 719 hospitals. We
      collected information on patient demographics and histories, diagnostic and
      staging methods, pathology, and initial treatment. RESULTS: Information on 40,909
      patients was obtained; 93% were smokers. Slightly more than half were older than
      70 years; 58.5% were male and 35% had adenocarcinoma. Comorbid conditions were
      present in 71.8% and 22% had a prior malignancy. A chest CT scan was performed in
      92% of patients and PET scans in 19.3%. Mediastinoscopy was performed in 20.3%.
      67.2% of patients had Stage III or IV disease. More of the Hispanic, Asian or
      Black patients than White had Stage IV disease (p<0.01). Treatment was
      multimodality in a little over 30% of patients. Surgery alone was primarily
      utilized for patients in Stage I or II. Choice of treatment correlated more with
      stage and age than comorbidities. CONCLUSION: Our results substantiated the
      pattern of increasing proportions of women with NSCLC and the increasing
      frequency of adenocarcinoma. Most patients presented with Stage III or IV
      disease. Ethnic minorities were more likely to present in late stage disease than
      Whites. Treatment strategies depended more on stage and age than comorbid burden.
      Older patients were less likely to receive surgery and more likely to be treated
      with radiation only or have no treatment.

PMID- 17451843
TI  - Peptide defenses of the Cascades frog Rana cascadae: implications for the
      evolutionary history of frogs of the Amerana species group.
AB  - The Cascades frog Rana cascadae belongs to the Amerana (or Rana boylii) group
      that includes six additional species from western North America (R. aurora, R.
      boylii, R. draytonii, R. luteiventris, R. muscosa, and R. pretiosa). R. cascadae
      is particularly susceptible to pathogenic microorganisms in the environment and
      populations have declined precipitously in parts of its range so that the
      protection afforded by dermal antimicrobial peptides may be crucial to survival
      of the species. Peptidomic analysis of norepinephrine-stimulated skin secretions
      led to the identification of six peptides with differential cytolytic activities
      that were present in high abundance. Structural characterization showed that they
      belonged to the ranatuerin-2 (one peptide), brevinin-1 (one peptide), and
      temporin (four peptides) families. Ranatuerin-2CSa
      (GILSSFKGVAKGVAKDLAGKLLETLKCKITGC) and brevinin-1CSa (FLPILAGLAAKIVPKLFCLATKKC)
      showed broad spectrum antibacterial activity (MIC</=32microM against Escherichia
      coli and Staphylococcus aureus) but only brevinin-1CSa was strongly hemolytic
      against human erythrocytes (LC(50)=5microM). The taxonomy of ranid frogs is
      currently in a considerable state of flux. The ranatuerin-2 gene is expressed in
      all members of the Amerana group studied to-date and cladistic analysis based
      upon a comparison of the amino acid sequences of this peptide indicates that R.
      cascadae, R. muscosa and R. aurora form a clade that is distinct from one
      containing R. draytonii, R. boylii, and R. luteiventris. This conclusion is
      consistent with previous analyses based upon comparisons of the nucleotide
      sequences of mitochondrial genes.

PMID- 17451844
TI  - Behavioral consequences of ovarian atrophy and estrogen replacement in the APPswe
      mouse.
AB  - Cognitive performance was evaluated in a longitudinal study of APPswe2576
      transgenic mice (APP) and a wildtype (WT) comparison group. Subgroups of the APP
      mice were treated with the ovarian toxicant 4-vinylcyclo-hexene diepoxide (VCD)
      at 60-75 days of age to induce ovarian atrophy and/or given estrogen (estradiol,
      4 microg/day) continuously by pellet from 76 days of age. APP mice had a
      generally poorer radial maze performance than WT at 4.5, 7.5, 10.5 and 15 months
      of age. In separate tests, APP mice had a slight motor impairment, higher
      incidence of homecage stereotypy, hyperactivity in an open field and reduced
      object exploration relative to the WT group. Ovarian atrophy led to better maze
      performance at 7.5 months. The effect of estrogen on maze performance with aging
      could not be effectively evaluated due to poor survival (30%) of these mice. No
      effects of ovarian atrophy or estrogen treatment were identified for amyloid-beta
      accumulation or plaque formation at 15 months. Long-term longitudinal studies in
      animal models are needed to explore the consequences of menopause and hormone
      replacement on Alzheimer's disease, but they are complicated by considerations of
      survival, pre-aging deficits, testing experience and selection of appropriate
      estrogen treatment levels.

PMID- 17451846
TI  - [An abnormal electrocardiogram in a drug addict patient].

PMID- 17451845
TI  - A structural equation modeling investigation of age-related variance in executive
      function and DTI measured white matter damage.
AB  - Cognitive changes in normal aging have been explained by the frontal-executive
      hypothesis, but the assumptions made by this hypothesis concerning the
      neurobiological causes are still a matter of debate. Executive functions (EF) may
      activate neural networks that include disparate grey matter regions, and rely on
      the integrity of white matter connections. In 118 adults (50-90 years old) from
      the GENIE study, white matter integrity was measured using diffusion tensor
      imaging, and information processing speed, fluid intelligence and EF were
      assessed. A theory-driven structural equation model was developed to test
      associations between variables. The model was revised, removing non-significant
      paths. The adjusted model explained well the covariance in our data; and
      suggested that the reduction in white matter integrity associated with age
      directly affected only working memory. Fluid intelligence was mediated by all
      measured cognitive variables. The results suggest that white matter integrity may
      be particularly important for abilities activating complex neural networks, as
      occurs in working memory. Integration of the information processing speed and
      frontal-executive hypotheses may provide important information regarding common,
      unique, and mediating factors in cognitive aging.

PMID- 17451847
TI  - [Gene and cell therapy in lower limb critical ischemia].

PMID- 17451848
TI  - [Pancytopenia related to low-dose methotrexate: study of five cases and review of
      the literature].
AB  - PURPOSE: The aim of this study is to report personal experience of pancytopenia
      related to low-dose methotrexate and to review the literature. METHODS: We
      included retrospectively all cases of pancytopenia related to low-dose
      methotrexate (<25 mg/week), followed between January 1997 and December 2006, in
      the university hospital of Strasbourg, France. RESULTS: Five women, mean age 75.6
      years, were included in the present study. Clinical manifestations included:
      symptomatic anemia (n=4), infection (n=3) and hemorrhagic manifestations (n=2);
      one patient had no feature. Mean hemoglobin concentration was 8,8 g/dl; mean
      white cell and platelet counts were 1,500 /mm(3) and 16,000 /mm(3), respectively.
      Potential risk factors were identified in all patients: renal failure and low
      serum albumin levels (n=5), anti-inflammatory drug intake (n=2), folate
      deficiency (n=4) and cobalamin deficiency (n=1). One patient died of septic and
      hemorrhagic cerebral complications. CONCLUSION: Pancytopenia related to tow-dose
      methotrexate is a rare but life-threatening disorder. Search and prevention of
      potential risk factors are required in all patients; determination of MTHFR
      genotype may be of several interests as folate supplementation.

PMID- 17451849
TI  - [Epidemiology of ischemic cardiovascular disease].

PMID- 17451850
TI  - Impact of a modified-live porcine reproductive and respiratory syndrome virus
      vaccine intervention on a population of pigs infected with a heterologous
      isolate.
AB  - The objectives of this study were to evaluate the effects of a therapeutic
      vaccine intervention with a modified-live porcine reproductive and respiratory
      syndrome virus (PRRSV) vaccine on the dynamics of a heterologous viral infection
      in a population of pigs, and to determine the clinical and virological response
      of previously exposed and vaccinated pigs against a second virulent heterologous
      challenge. A population of 320 pigs were infected with a field isolate, PRRSV MN
      30100, alone or followed by Ingelvac PRRS MLV vaccine administered one to three
      times at 30 days intervals beginning 1 week after infection. Vaccine intervention
      reduced the duration of viral shedding, but did not reduce the viral load in
      tissues or the proportion of persistently infected pigs. A different and highly
      virulent field isolate, MN-184, was then given as a heterologous viral challenge
      at 97 days after first exposure. Previously infected and vaccinated pigs showed a
      significant reduction in clinical signs and enhanced weight gain after the highly
      virulent challenge with PRRSV MN-184, but infection with and shedding of the
      challenge isolate were not prevented.

PMID- 17451851
TI  - Building a place for the father as an ally for breast feeding.
AB  - OBJECTIVE: to analyse the opinions of men and women on the father's participation
      in breast feeding. DESIGN: a qualitative and exploratory study, using the content
      analysis method, on its thematic modality. Data were collected at discussion
      groups that answered the following questions: which meanings and feelings are
      related to father's involvement in breast feeding? Which factors help or obstruct
      the act of breast feeding? How do fathers participate in breast feeding? SETTING:
      three discussion groups took place during the event 'The man as an ally in breast
      feeding process: is that the question?', supported by the Federal University of
      Pernambuco, Brazil. PARTICIPANTS: 11 men and nine women attended the event. Of
      the men, two had more than one child and five had babies who were being breast
      fed. Among the women, all were mothers and three were breast feeding. FINDINGS:
      four thematic nuclei emerged from the performed analysis, which was also based in
      the historical, social and cultural process of fatherhood: involvement in the
      pregnancy-puerperal cycle; feelings and meanings of breast feeding; meanings of
      breast feeding in public; and ways to include father in the breast-feeding
      process. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: fathers participating in
      breast feeding considered it to be a brief period in the process of fatherhood.
      Behaviours of ambivalence, conflict, exclusion, insecurity and concern towards
      breast feeding were revealed. There was a perception of the nursing mother as a
      sexless being. However, the participants also suggested ways of including fathers
      in the process of breast feeding. According to the participants, they could (1)
      provide a favourable environment for the mother and baby; (2) participate more
      during pregnancy and birth; (3) help with domestic chores; (4) develop
      parenthood; and (5) be present during breast feeding. These suggestions may
      function as foundations for health staff to develop programmes, in order to
      involve fathers in breast feeding. This could result in a contribution to improve
      the practice and duration of that process.

PMID- 17451852
TI  - "Life is still going on": reproductive intentions among HIV-positive women and
      men in South Africa.
AB  - This article reports on qualitative research investigating HIV positive
      individuals' reproductive intentions and their influencing factors in Cape Town,
      South Africa. In-depth interviews were held with 61 HIV positive women and men;
      at the time of interview, half had been receiving antiretroviral treatment (ART)
      for over 6 months and half were not receiving ART. Being HIV positive modified
      but did not remove reproductive desires, and diversity existed in reproductive
      intentions. Some HIV positive individuals wished to avoid pregnancy. Fears of
      partner and infant infection and having a previously infected baby were important
      factors deterring some individuals from considering having children. There was
      also strongly perceived community disapproval associated with HIV and
      reproduction. Strong desires to experience parenthood, mediated by prevailing
      social and cultural norms that encouraged childbearing in society more broadly,
      were reported by others. Motherhood was an important component of married women's
      identity and important for women's social status. Family, husbands' and societal
      expectations for childbearing were important influences on women's reproductive
      intentions, for some counterbalancing HIV as a factor discouraging reproduction.
      There was evidence that prevention of perinatal transmission programs in
      combination with ART may alter women and men's attitudes in favour of
      childbearing. Most HIV positive women had not discussed their reproductive
      desires and intentions with health care providers in HIV care or general health
      services because of anticipated negative reactions. The few who had done so
      perceived the counselling environment to be mostly unsupportive of open
      discussion on these issues. The findings highlight the need for explicit policies
      recognizing reproductive rights and choice. They support the need for health
      counselling and service interventions that advance safer and healthier
      reproductive options for HIV positive individuals in this region of the world
      which is experiencing a generalised and advanced HIV/AIDS pandemic.

PMID- 17451853
TI  - Regulating health care in low- and middle-income countries: Broadening the policy
      response in resource constrained environments.
AB  - Regulation is traditionally seen as the use of bureaucratic and administrative
      controls by government to correct market failure. Yet traditional methods such as
      licensing and certification frequently fail to control behaviour because of the
      limited resources available to government in low- and middle-income countries,
      and because of the powerful countervailing incentives that encourage deviant
      behaviour to continue. It is increasingly being realised, therefore, that goals
      of policy can sometimes be achieved more efficiently by involving other actors in
      the regulatory mechanism. In addition, a more flexible view of regulatory tools
      and strategies may enable governments, particularly in resource constrained
      environments, to utilise a much wider range of administrative controls and market
      enhancing incentives. The review suggests a wide range of tools that may be
      utilised to encourage better behaviour. These require that governments become
      aware of the need to reinforce controls with enabling incentives, utilise
      external standards where local measures are deemed inadequate and promote greater
      access to information on standards and services to consumers and providers.

PMID- 17451854
TI  - On physician well being-you'll get by with a little help from your friends.
AB  - This study identifies positive and negative factors associated with physician
      well being. We collected two sets of data from physicians at a university-based
      Department of Medicine in Western Canada. First, we conducted exploratory, in
      depth interviews with 54 physicians to identify factors associated with their
      well being. Participants explained that certain aspects of their work are
      demanding and negatively related to their well being, whereas other 5 factors are
      more enabling and contribute positively. Second, we mailed a structured
      questionnaire including measures of the key factors identified in the physician
      interviews to all physicians in the same Department of Medicine. Multivariate
      analysis was used to assess the extent to which the factors identified in the
      interviews are significantly related to physicians' well being. The findings show
      the importance of co-worker support, both in terms of being directly related to
      physician well being as well as buffering the negative effects of work demands.
      We discuss several important implications for physicians and the organizations
      that employ them in understanding the factors related to physician well being. In
      addition, patient interactions appear to be both a key source of stress and a
      major source of satisfaction in physicians' daily work lives.

PMID- 17451855
TI  - Why are early maturing girls less active? Links between pubertal development,
      psychological well-being, and physical activity among girls at ages 11 and 13.
AB  - Previous research has shown that early maturing girls at age 11 have lower
      subsequent physical activity at age 13 in comparison to later maturing girls.
      Possible reasons for this association have not been assessed. This study examines
      girls' psychological response to puberty and their enjoyment of physical activity
      as intermediary factors linking pubertal maturation and physical activity.
      Participants included 178 girls who were assessed at age 11, of whom 168 were
      reassessed at age 13. All participants were non-Hispanic white and resided in the
      US. Three measures of pubertal development were obtained at age 11 including
      Tanner breast stage, estradiol levels, and mothers' reports of girls' development
      on the Pubertal Development Scale (PDS). Measures of psychological well-being at
      ages 11 and 13 included depression, global self-worth, perceived athletic
      competence, maturation fears, and body esteem. At age 13, girls' enjoyment of
      physical activity was assessed using the Physical Activity Enjoyment Scale and
      their daily minutes of moderate-to-vigorous physical activity (MVPA) were
      assessed using objective monitoring. Structural Equation Modeling was used to
      assess direct and indirect pathways between pubertal development at age 11 and
      MVPA at age 13. In addition to a direct effect of pubertal development on MVPA,
      indirect effects were found for depression, global self-worth and maturity fears
      controlling for covariates. In each instance, more advanced pubertal development
      at age 11 was associated with lower psychological well-being at age 13, which
      predicted lower enjoyment of physical activity at age 13 and in turn lower MVPA.
      Results from this study suggest that programs designed to increase physical
      activity among adolescent girls should address the self-consciousness and
      discontent that girls' experience with their bodies during puberty, particularly
      if they mature earlier than their peers, and identify activities or settings that
      make differences in body shape less conspicuous.

PMID- 17451856
TI  - EEG mu rhythm and imitation impairments in individuals with autism spectrum
      disorder.
AB  - Imitation ability has consistently been shown to be impaired in individuals with
      autism. A dysfunctional execution/observation matching system has been proposed
      to account for this impairment. The EEG mu rhythm is believed to reflect an
      underlying execution/observation matching system. This study investigated
      evidence of differential mu rhythm attenuation during the observation, execution,
      and imitation of movements and examined its relation to behaviorally assessed
      imitation abilities. Fourteen high-functioning adults with autism spectrum
      disorder (ASD) and 15 IQ- and age-matched typical adults participated. On the
      behavioral imitation task, adults with ASD demonstrated significantly poorer
      performance compared to typical adults in all domains of imitation ability. On
      the EEG task, both groups demonstrated significant attenuation of the mu rhythm
      when executing an action. However, when observing movement, the individuals with
      ASD showed significantly reduced attenuation of the mu wave. Behaviorally
      assessed imitation skills were correlated with degree of mu wave attenuation
      during observation of movement. These findings suggest that there is
      execution/observation matching system dysfunction in individuals with autism and
      that this matching system is related to degree of impairment in imitation
      abilities.

PMID- 17451857
TI  - Effects of normal aging on memory for multiple contextual features.
AB  - Twenty-four younger (18-35 years) and 24 older adult participants (65 or older)
      were exposed to three experimental conditions involving the memorization words
      and their associated contextual features, with contextual feature complexity
      increasing from Conditions 1 to 3. In Condition 1, words presented varied only on
      one binary feature (color, size, or character), while in Conditions 2 and 3,
      words presented varied on two and three binary features, respectively. Each
      condition was carried out as follows: (1) learning of a word list; (2) encoding
      of words and their contextual features; (3) delay; and (4) memory for contextual
      features through a discrimination task. Results indicated that young adults
      discriminated more features than older adults on all conditions. In both age
      groups, contextual feature discrimination accuracy decreased as the number of
      features increased. Moreover, older adults demonstrated near floor performance
      when tested with two or more binary features. We conclude that increasing context
      complexity strains attentional resources.

PMID- 17451858
TI  - Aberrant DNA methylation and gene expression in livers of newborn mice
      transplacentally exposed to a hepatocarcinogenic dose of inorganic arsenic.
AB  - Our prior work showed that brief exposure of pregnant C3H mice to inorganic
      arsenic-induced hepatocellular carcinoma (HCC) formation in adult male offspring.
      The current study examined the early hepatic events associated with this
      oncogenic transformation. Pregnant mice were exposed to a known carcinogenic dose
      of arsenic (85 ppm) in the drinking water from gestation days 8 to 18. The dams
      were allowed to give birth and liver samples from newborn males were analyzed for
      arsenic content, global DNA methylation and aberrant expression of genes relevant
      to the carcinogenic process. Arsenic content in newborn liver reached 57 ng/g wet
      weight, indicating arsenic had crossed the placenta, reached the fetal liver and
      that significant amounts remained after birth. Global methylation status of
      hepatic DNA was not altered by arsenic in the newborn. However, a significant
      reduction in methylation occurred globally in GC-rich regions. Microarray and
      real-time RT-PCR analysis showed that arsenic exposure enhanced expression of
      genes encoding for glutathione production and caused aberrant expression of genes
      related to insulin growth factor signaling pathways and cytochrome P450 enzymes.
      Other expression alterations observed in the arsenic-treated male mouse newborn
      liver included the overexpression of cdk-inhibitors and stress response genes
      including increased expression of metallothionein-1 and decreased expression of
      betaine-homocysteine methyltransferase and thioether S-methyltransferase. Thus,
      transplacental exposure to arsenic at a hepatocarcinogenic dose induces
      alterations in DNA methylation and a complex set of aberrant gene expressions in
      the newborn liver, a target of arsenic carcinogenesis.

PMID- 17451860
TI  - Influence of an anion-binding site in the stabilization of halophilic malate
      dehydrogenase from Haloarcula marismortui.
AB  - Halophilic proteins have evolved to be soluble, stable and active in high salt
      concentration. Crystallographic studies have shown that surface enrichment by
      acidic amino acids is a common structural feature of halophilic proteins. In
      addition, ion-binding sites have also been observed in most of the cases. The
      role of chloride-binding sites in halophilic adaptation was addressed in a site
      directed mutagenesis study of tetrameric malate dehydrogenase from Haloarcula
      marismortui. The mutation of K 205, which is involved in an inter-subunit
      chloride-binding site, drastically modified the enzyme stability in the presence
      of KCl, but not in the presence of KF. The oligomeric state of the [K205A] mutant
      changes with the nature of the anion. At high salt concentration, the [K205A]
      mutant is a dimer when the anion is a chloride ion, whereas it is a tetramer when
      the fluoride ion is used. The results highlight the role of anion-binding sites
      in protein adaptation to high salt conditions.

PMID- 17451859
TI  - The in vitro metabolism of a pyrethroid insecticide, permethrin, and its
      hydrolysis products in rats.
AB  - The in vitro metabolism of permethrin and its hydrolysis products in rats was
      investigated. Cis- and trans-permethrin were mainly hydrolyzed by liver
      microsomes, and also by small-intestinal microsomes of rats. trans-Permethrin was
      much more effectively hydrolyzed than the cis-isomer. When NADPH was added to the
      incubation mixture of the liver microsomes, three metabolites, 3-phenoxybenzyl
      alcohol (PBAlc), 3-phenoxybenzaldehyde (PBAld) and 3-phenoxybenzoic acid
      (PBAcid), were formed. However, only PBAlc was formed by rat liver microsomes in
      the absence of cofactors. The microsomal activities of rat liver and small
      intestine were inhibited by bis-p-nitrophenyl phosphate, an inhibitor of
      carboxylesterase (CES). ES-3 and ES-10, isoforms of the CES 1 family, exhibited
      significant hydrolytic activities toward trans-permethrin. When PBAlc was
      incubated with rat liver microsomes in the presence of NADPH, PBAld and PBAcid
      were formed. The NADPH-linked oxidizing activity was inhibited by SKF 525-A. Rat
      recombinant cytochrome P450, CYP 2C6 and 3A1, exhibited significant oxidase
      activities with NADPH. When PBAld was incubated with the microsomes in the
      presence of NADPH, PBAcid was formed. CYP 1A2, 2B1, 2C6, 2D1 and 3A1 exhibited
      significant oxidase activities in this reaction. Thus, permethrin was hydrolyzed
      by CES, and PBAlc formed was oxidized to PBAld and PBAcid by the cytochrome P450
      system in rats.

PMID- 17451861
TI  - The antitumor effects of interferon: a personal history.
AB  - Early experiments showed that administration of mouse interferon preparations
      inhibited the development of viral-induced or spontaneous viral associated
      leukemias in mice. Interferon alpha/beta was also shown to inhibit the growth of
      transplantable tumors of different origins in all strains of mice tested. The
      finding that interferon alpha/beta inhibited the growth of sublines of tumors
      selected for resistance to interferon alpha/beta indicated the role of interferon
      induced host mechanisms in the antitumor effects observed. The different host
      antitumor mechanisms and especially the interaction of interferon alpha/beta with
      the immune system have been briefly discussed. Injection of mice with a
      neutralizing antibody to interferon alpha/beta demonstrated the essential role of
      endogenous interferon alpha/beta in the defense of the mouse against the
      development of syngeneic, allogeneic and xenogeneic tumors.

PMID- 17451862
TI  - The dsRNA protein kinase PKR: virus and cell control.
AB  - The IFN-induced double-stranded RNA-dependent protein kinase (PKR) is one of the
      four mammalian serine-threonine kinases (the three others being HRI, GCN2 and
      PERK) that phosphorylate the eIF2 alpha translation initiation factor, in
      response to stress signals, mainly as a result of viral infections. eIF2 alpha
      phosphorylation results in arrest of translation of both cellular and viral
      mRNAs, an efficient way to inhibit virus replication. The particularity of PKR is
      to activate by binding to dsRNA through two N terminal dsRNA binding motifs
      (dsRBM). PKR activation during a viral infection represents a threat for several
      viruses, which have therefore evolved to express PKR inhibitors, such as the
      Vaccinia E3L and K3L proteins. The function of PKR can also be regulated by
      cellular proteins, either positively (RAX/PACT; Mda7) or negatively (p58IPK,
      TRBP, nucleophosmin, Hsp90/70). PKR can provoke apoptosis, in part through its
      ability to control protein translation, but the situation appears to be more
      complex, as NF-kappaB, ATF-3 and p53 have also been implicated. PKR-induced
      apoptosis involves mainly the FADD/caspase 8 pathway, while the mitochondrial
      APAF/caspase 9 pathway is also engaged. As a consequence of the effects of PKR on
      translation, transcription and apoptosis, PKR can function to control cell growth
      and cell differentiation, and its activity can be controlled by the action of
      several oncogenes.

PMID- 17451863
TI  - Can brain natriuretic peptide predict outcome after cardiac arrest? An
      observational study.
AB  - BACKGROUND: No accurate, independent biomarker has been identified that could
      reliably predict neurological outcome early after cardiac arrest. We speculated
      that brain natriuretic peptide (BNP) measured at hospital admission may predict
      patient outcome. METHODS: BNP-levels were measured in 155 comatose cardiac arrest
      survivors (108 male, 58 years [IQR 49-68]) (median time to ROSC 11min; IQR 20-30)
      during a 6-year study period. Cardiovascular co-morbidities and resuscitation
      history were assessed according to the Utstein-style and patients were followed
      for 6-month neurological outcome measured by cerebral performance category (CPC)
      and survival. RESULTS: Seventy patients (45%) suffered from unfavourable
      neurological outcome and 79 deaths (51%) occurred during the first 6 months. BNP
      was significantly associated with an adverse neurological outcome and mortality,
      independent of the prearrest health condition and cardiac arrest characteristics
      (median 60 pg/ml; IQR 10-230). Adjusted odds ratios for poor neurological outcome
      at 6 months were 1.14 (95% CI 0.51-2.53), 1.76 (95% CI 0.80-3.88) and 2.25 (95%
      CI 1.05-4.81), for increasing quartiles of BNP as compared to the lowest
      quartile. Adjusted odds ratios for mortality until 6 months were 1.09 (95% CI
      0.35-3.40), 2.81 (0.80-9.90) and 4.7 (1.27-17.35) compared to the lowest
      quartile, respectively. CONCLUSION: Brain natriuretic peptide levels on admission
      predict neurological outcome at 6 months and survival after cardiac arrest.

PMID- 17451864
TI  - Ventricular fibrillation induced by transoesophageal cardiac pacing: a new model
      of cardiac arrest in rats.
AB  - OBJECTIVE: To investigate whether transoesophageal cardiac pacing can induce
      ventricular fibrillation (VF) and how long the cardiac pacing has to be sustained
      to prevent the reversion of the VF induced. METHODS: A pacing electrode was
      inserted orally into the oesophagus and high-frequency ventricular pacing was
      performed so as to elicit VF in 25 Sprague-Dawley rats. Incidences of VF and time
      of cardiac pacing were observed and recorded. Four minutes after onset of VF
      cardiopulmonary resuscitation (CPR) was initiated. RESULTS: A short interval of
      high-frequency ventricular pacing caused an immediate drop of blood pressure,
      loss of pulse and increase of right atrial pressure in the same time frame. When
      the cardiac pacing was terminated, VF was elicited at least once or more than
      once in all of the 25 rats. However, the VF elicited by the burst stimulation
      could be defibrillated spontaneously. With the prolongation (120-180 s) of
      cardiac pacing, the incidence of defibrillation of VF decreased from 100 to 0%.
      VF persisted in 19 of 25 animals, developed into asystole in 5 of 25 animals and
      converted into pulseless electrical activity in 1 of 25 animals prior to CPR.
      Following CPR 22 of 25 animals were resuscitated. CONCLUSIONS: Transoesophageal
      cardiac pacing can induce VF in rats. However, the cardiac pacing is required for
      at least 120-180 s to ensure that VF does not spontaneously convert. We can use
      the technique to establish a new and simpler rat cardiac arrest (CA) model, which
      may facilitate experimental investigation on CPR.

PMID- 17451865
TI  - The number, subset and source of cells injected remain critical factors affecting
      engraftment after in-utero stem cell transplantation via the intracelomic route.

PMID- 17451866
TI  - Analysis of insulin amyloid fibrils by Raman spectroscopy.
AB  - The formation of amyloid fibrils from insulin is investigated using drop-coating
      deposition-Raman (DCDR) difference spectroscopy and atomic force microscopy
      (AFM). Fibrils formed using various co-solvents and heating cycles are found to
      induce the appearance of Raman difference peaks in the amide I (approximately
      1675 cm(-1)), amide III (approximately 1220 cm(-1)), and peptide backbone
      (approximately 1010 cm(-1)), consistent with an increase in beta-sheet content.
      Comparisons of results obtained from fibrils in either H2O or D2O suggest that
      the NH/ND stretch bands (at approximately 3300 cm(-1)/ approximately 2400 cm(-1))
      are also enhanced in intensity upon fibril formation. If there is any water
      trapped in the core of the fibrils its OH/OD Raman intensity is too small to be
      detected in the presence of the stronger NH/ND bands which appear in the same
      region. AFM is used to confirm the formation of fibrils of about 5 nm diameter
      (and various lengths).

PMID- 17451867
TI  - Validation of isovolumic relaxation flow propagation velocity as an index of
      ventricular relaxation.
AB  - To test the applicability of isovolumic relaxation flow propagation velocity
      (IRFPV) as an indicator of relaxation, 38 patients undergoing cardiac
      catheterization for chest pain were included. The time constant of isovolumic
      left ventricular (LV) pressure decline (tau) had a significant correlation with
      the LV end-diastolic pressure, the peak negative dp/dt, the LV end-diastolic
      dimension, the fractional shortening, the late diastolic transmitral flow
      velocity, the early and late diastolic mitral annular velocities, the rapid
      filling flow propagation velocity, and the natural logarithms of heart rate,
      ejection fraction, LV end-systolic dimension and IRFPV (r = -0.773, p < 0.001).
      IRFPV was selected as the major independent determinant of tau, explaining 46% of
      its variance. In prediction of tau > or =42 ms, the sensitivity and specificity
      were 100% and 83% for IRFPV < or =104 cm/s, 77% and 67% for the rapid filling
      flow propagation velocity < or =50 cm/s, and 58% and 67% for the early diastolic
      mitral annular velocity < or =8 cm/s, respectively. In conclusion, our data
      suggest that IRFPV could be a better marker of LV relaxation than other
      parameters, as the rapid filling flow propagation velocity or the early diastolic
      mitral annular velocity.

PMID- 17451868
TI  - The onset of microbubble vibration.
AB  - A linear relationship between the relative expansion of an off-resonance
      ultrasound contrast microbubble and low acoustic pressures is expected. In this
      study, high-speed optical recordings of individual phospholipid-coated
      microbubbles were used to investigate this relationship for microbubbles ranging
      from 2 to 11 microm and for acoustic pressures ranging from 20 to 250 kPa at a
      driving frequency of 1.7 MHz. For microbubbles larger than 5 microm, the relative
      expansion (DeltaD/D0) increased linearly with applied acoustic pressure, starting
      at the origin. The response of smaller microbubbles (<5 microm) also increased
      linearly with the applied acoustic pressure. However, linearity started at an
      acoustic pressure threshold value of 30 to 120 kPa for the different individual
      microbubbles. Below these pressure values, little or no oscillation was observed.
      The results may be explained by size-dependent mechanical properties of the
      phospholipid shells. An imaging technique such as power modulation imaging could
      profit from the presence of an acoustic pressure threshold in the microbubble
      response.

PMID- 17451869
TI  - The impact of physiological motion on tissue tracking during radiation force
      imaging.
AB  - The effect of physiological motion on the quality of radiation force elasticity
      images has been investigated. Experimental studies and simulated images were used
      to investigate the impact of motion effects on image quality metrics over a range
      of clinically realistic velocity and acceleration magnitudes. Evaluation criteria
      included motion filter effectiveness, image signal-to-noise ratio (SNR) and the
      contrast-to-noise ratio (CNR) of a stiff inclusion embedded in a homogeneous
      background material. Two transmit frequencies (2.5 and 4.4 MHz) were analyzed and
      contrasted in terms of image quality over a range of target motions. Results
      indicate that situations may exist where liver and cardiac motion magnitudes lead
      to poor image quality, but optimized transducer orientations may help suppress
      motion artifacts if some a priori information concerning target motion
      characteristics is known. In the presence of significant target motion, utilizing
      a lower transmit frequency can improve SNR and CNR in elasticity images.

PMID- 17451870
TI  - Harmonic imaging using multitone nonlinear coding.
AB  - We present a new method that uses nonlinear properties of tissue to improve
      contrast-to-noise ratio. In our novel method, the acoustic source is activated
      with two tone-bursts (2.2 and 4.4 MHz), with specially designed polarization of
      the individual tone-burst. This new approach is called multitone nonlinear coding
      (MNC) because the choice of polarization of both tones (and their amplitudes),
      allowing optimization of the receiving properties, depends on the nonlinear
      properties of tissue. The calculations were done for two tone-bursts propagating
      in the tissue-like glossy medium with absorption of 7 Np/m x MHz. The method was
      experimentally verified by scanning the incident pulses propagating in soft
      tissue and by scanning the thread phantom immersed in water. The concept of the
      virtual fields was introduced to explain abilities and properties of pulse
      inversion and MNC and to compare the two methods. Comparison of the spatial field
      distribution obtained using MNC with the conventional harmonic imaging approach,
      in which the second harmonic is used to reconstruct the image, is presented. It
      was shown that, for the same peak pressure amplitude, the resulting mechanical
      index was about 40% lower for MNC, lateral resolution was 10% to 30% better and,
      what seems to be the most encouraging, the signal gain was up to eight times
      higher than pulse inversion.

PMID- 17451871
TI  - Repeated negative prostate biopsies with persistently elevated or rising PSA: a
      modern urologic dilemma.

PMID- 17451872
TI  - Biomedical implications of information processing in chemical systems: non
      classical approach to photochemistry of coordination compounds.
AB  - Analogies between photoactive nitric oxide generators and various electronic
      devices: logic gates and operational amplifiers are presented. These analogies
      have important biological consequences: application of control parameters allows
      for better targeting and control of nitric oxide drugs. The same methodology may
      be applied in the future for other therapeutic strategies and at the same time
      helps to understand natural regulatory and signaling processes in biological
      systems.

PMID- 17451873
TI  - Cryptogenic localization related epilepsy in children from a tertiary outpatient
      clinic: is neurological and neuropsychological outcome predictable?
AB  - OBJECTIVES: Up to one-third of the children with epilepsy are diagnosed with
      cryptogenic localization related epilepsy (CLRE). As yet, there is a lack of
      studies that specify the short- and long-term prognosis for this group. In this
      study, we systematically established neurological outcome (represented by seizure
      frequency) as well as neuropsychological outcome in a cohort of 68 children with
      CLRE who had been referred to our tertiary outpatient clinic. Also, we analysed
      correlations with risk and prognostic factors. PATIENTS AND METHODS: A systematic
      cross-sectional open clinical and non-randomized design was used including 68
      children admitted to our epilepsy centre in a child neurological programme
      between January 1999 and December 2004. A model was defined, distinguishing risk
      factors with a potential effect on epileptogenesis (history of febrile seizures,
      family history of epilepsy, history of early mild development delay and serious
      diagnostic delay) and prognostic factors, with a potential effect on the course
      of the epilepsy (neurological symptoms or soft signs, age at onset, duration of
      epilepsy, seizure type, percentage of time with epileptiform activity,
      localization of epileptiform activity, treatment history and treatment duration).
      Seizure frequency was used as the primary outcome variable, whereas three
      neuropsychological outcomes (IQ, psychomotor delay and educational delay) were
      used as secondary outcome variables. RESULTS: The children experienced a broad
      range of seizure types with the 'absence-like' complex partial seizure as the
      most commonly occurring seizure type. Almost half of the children of the study
      sample had a high seizure frequency. They experienced several seizures per month,
      week or even daily seizures. Also a substantial impact on neuropsychological
      outcome was observed. Mean full scale IQ was 87.7, mean academic delay was almost
      1 school year and 27 children showed psychomotor delay on the Movement ABC. Only
      'having more than one seizure type' showed a prognostic value for seizure
      frequency, and no factors were found to be correlated with the secondary outcome
      measures. None of the risk factors show a differential impact on seizure outcome.
      CONCLUSION: CLRE has a non-predictable course; clinical variability is high and
      prognosis in many children with CLRE is obscure. Having more than one seizure
      type was the only factor correlated to seizure frequency. Further longitudinal
      studies are needed.

PMID- 17451874
TI  - Expression of the high mobility group A family member p8 is essential to
      maintaining tumorigenic potential by promoting cell cycle dysregulation in
      LbetaT2 cells.
AB  - The mechanism by which the HMGA protein p8 facilitates tumorigenesis may be cell
      cycle dysregulation. Control- (C) LbetaT2 cells, which express p8, form tumors at
      a rate five-times faster than p8-knockdown (p8-KD)-LbetaT2 cells. In association
      with this heightened tumorigenic potential, p8-expressing C-LbetaT2 cells avoid
      G(0)/G(1) arrest and become genetically unstable while p8-KD-LbetaT2 cells arrest
      in G(0)/G(1), become senescent upon overgrowth, and maintain a diploid
      population. These phenotypic changes correspond to altered cell cycle regulation
      at the G(1)-to-S transition that may be due to p8-mediated changes in expression
      of the Cip/Kip family members of cell cycle inhibitors, p21, p27, and p57.

PMID- 17451875
TI  - Electrolytic recovery of chromium salts from tannery wastewater.
AB  - Tannery wastewater collected from a local leather industry in Peshawar, Pakistan
      was subjected to DC electrolysis in a simple cell having two static sheet
      electrodes and stirring assembly after proper dilution and adjustment to desired
      conditions. One percent HNO(3) and 1% NaHCO(3) were used as electrolytes and pH
      adjusters. The latter salt also worked as sodium source for anodic deposition of
      Na(2)Cr(2)O(7). Various combinations of electrodes were tested and conditions
      optimized for best electrode couple with increased recovery and removal of
      chromium in the form of Cr(OH)(3) and/or Na(2)Cr(2)O(7) at cathode and anode,
      respectively. The recovery of 99% chromium was achieved after 2h electrolysis at
      a cell potential of 1.0 V, pH 5.0 and stirring rate of 500 rpm using Pb sheet as
      anode and Cu sheet as cathode. The most interesting and novel finding of this
      work was the recovery of the mentioned salt(s) alone at Cu cathode or Pb anode or
      collectively at both electrodes by proper control of pH. Such treatment not only
      minimizes the environmental water pollution, but results in the formation of
      useful products employed for recycling purpose in tannery or other related
      industry to make the process economical.

PMID- 17451876
TI  - Results of interlaboratory comparisons of column percolation tests.
AB  - Laboratory leaching tests may be used for source term determination as a basis
      for risk assessment for soil-groundwater pathway (leachate forecast) on
      contaminated sites in Germany. Interlaboratory comparisons on the evaluation of
      the reproducibility of column percolation tests were conducted within the
      framework of an integrated R+D program using three waste reference materials. The
      interlaboratory comparisons of column percolation tests showed good
      reproducibility of the results for inorganic and organic parameters as well as
      for the accompanying parameters. This is due to the stipulations concerning the
      time of contact between leachant and sample material as well as the sample
      placement in the columns. Different column dimensions used by the participants of
      the interlaboratory comparisons did not have any substantial influence on the
      column test results.

PMID- 17451877
TI  - Relief of post-herpetic neuralgia by surgical removal of painful skin: 5 years
      later.
AB  - Surgical removal of painful skin was first attempted as a treatment for chronic
      intractable post-herpetic neuralgia (PHN) more than a century ago, but long-term
      follow-up has rarely been reported. A patient who underwent surgical excision of
      294cm(2) of thoracic skin comprising the entire area of pain and allodynia in
      October 2000 has been followed for 5.5years post-surgery. Our initial report
      presented evidence of benefit in the form of reduced pain, elimination of
      allodynia, and reduced medication consumption during the first post-operative
      year. Unfortunately, pain steadily increased and now exceeds pre-surgery levels
      despite increased medication use. Pain topography and characteristics are
      different from pre-surgery and may relate to the pathophysiology of PHN. Skin
      resection cannot be recommended as a treatment for PHN.

PMID- 17451878
TI  - Mental disorders in people with chronic pain: an international perspective.

PMID- 17451879
TI  - Usefulness and limitations of quantitative sensory testing: clinical and research
      application in neuropathic pain states.

PMID- 17451880
TI  - Decision analysis of medical and surgical treatments for trigeminal neuralgia:
      how patient evaluations of benefits and risks affect the utility of treatment
      decisions.
AB  - Trigeminal neuralgia (TN) is a rare form of neuropathic facial pain characterised
      by severe, paroxysmal pains in the face. Little is known about the decision
      process in treatment of TN, and management with anti-epileptic drugs or surgical
      procedures carries risks of side effects, recurrence and complications. One
      hundred fifty-six previously diagnosed TN patients completed an adapted time
      trade-off utility measurement questionnaire to ascertain how they valued the
      potential outcomes from various surgical and medical treatments. The decision
      analysis revealed that microvascular decompression surgery (MVD) offered the best
      chance of improved quality of life or highest maximum expected utility (MEU). MVD
      (MEU=16.08 out of a possible 20) was closely followed by balloon compression
      (MEU=15.97), percutaneous glycerol rhizolysis (MEU=15.61) and then radiofrequency
      thermocoagulation (MEU=14.93). Medication offered the least optimal chance of
      improved quality of life (MEU=14.61). The difference between the highest (MVD)
      and lowest scoring treatments (medication) was 7.3% (1.46/20). These results were
      sensitive to some utility values, meaning the preferred treatment is changed by
      the values patients assign to outcomes. As surgical techniques narrowly offer the
      highest chance of maximising patient quality of life, all patients with TN should
      consider surgery. However, surgery is not right for everyone, and patients should
      be informed about their full range of choices. Treatment decisions must take
      place after careful consideration of the values patients place on benefits and
      risks of treatment.

PMID- 17451881
TI  - Molecular characterization of Cryptosporidium and Giardia isolates from cattle
      from Portugal.
AB  - Fecal samples from 291 calves and 176 adult cattle in Northern Portugal were
      screened for Cryptosporidium and Giardia using a formalin-ethyl acetate
      concentration method. Acid-fast staining techniques for Cryptosporidium oocyst
      identification and direct microscopic observation of fecal smears for Giardia
      cyst identification were performed so as immunofluorescence microscopy
      examination. Polymerase chain reaction methods were employed to determine the
      genotype of each isolate. Molecular characterization was performed using
      amplification and sequencing of the hsp70 and 18SrRNA genes of Cryptosporidium
      and beta-giardin gene and glutamate dehydrogenase for assemblage determination of
      Giardia duodenalis. Seventy-four out of 291 calves (25.4%) and 8 out of 176 adult
      bovines (4.5%) were positive for Cryptosporidium. Forty-one out of 291 calf
      samples (14.1%) and 1 out of 176 adults samples (0.57%) were positive for
      Giardia. From the Cryptosporidium positive samples we obtained 63 isolates from
      calves samples and 7 isolates from adult samples. Additionally, Giardia was
      isolated in 13 out of 41 positive samples from calves and it was also possible to
      isolate Giardia from the positive adult sample. Molecular characterization of the
      Cryptosporidium and Giardia isolates showed us that C. parvum and G. duodenalis
      assemblage E were the prevalent species. C. parvum may infect humans,
      representing a potential public health risk. On the other hand, the assemblages B
      and A2 of Giardia, previously described in humans, were here identified in
      cattle. Further studies will be needed for determine the importance of cattle as
      carrier of zoonotic assemblages of G. duodenalis.

PMID- 17451882
TI  - Isolation and molecular detection of Neospora caninum from naturally infected
      sheep from Brazil.
AB  - Neospora caninum was isolated from a naturally infected sheep from Brazil by
      bioassay in dogs. Approximately 70g of brain from each of two 4-month-old sheep
      with indirect fluorescent antibodies (>or=1:50) to N. caninum was offered to a
      different IFAT negative dog (Sheep n. 302, IFAT 1:400-Dog 1 and Sheep n. 342,
      IFAT 1:50-Dog 2). Parasite DNA was detected in both sheep brains using a PCR
      targeting the Nc-5 gene of N. caninum. Shedding of Neospora-like oocysts was
      noticed only in Dog 1, from 10 days post-inoculation (PI) to 25 days PI (a total
      of approximately 27,600 oocysts). Seventy days after infection, Dog 1 was
      euthanized and brain/cerebellum and medulla were collected and submitted to
      molecular methods, as were the oocysts, to confirm the identity of the isolate.
      Serum samples collected weekly from both dogs from the infection to the end of
      the experimental period had no antibodies anti-N. caninum by IFAT (<1:50).
      Oocysts, brain/cerebellum and medulla specimens of Dog 1 proved positive by a PCR
      assay targeting the Nc-5 gene of N. caninum. In addition, the oocysts have the
      DNA amplified by a PCR based on primers directed to the common toxoplasmatiid
      ITS1 sequence. The PCR products of ITS1 were sequenced, confirming again the
      isolate as N. caninum. Oocysts were also orally inoculated in two Swiss white
      mice two Mongolian gerbils (Meriones ungulatus) and two large vesper mice
      (Calomys callosus) (10(3)oocysts/animal). The rodents were sacrificed 2 months
      PI, and fresh preparations of brains showed Neospora thick-walled cysts in gerbil
      brains, but molecular detection using the Nc-5 PCR assay revealed DNA parasite in
      gerbil and also C. callosus brains. This is the first report of isolation and
      sequencing of N. caninum from a Brazilian sheep and the first report of molecular
      detection of N. caninum from C. callosus.

PMID- 17451883
TI  - Quantitative study of the drug efflux kinetics from sensitive and MDR human
      breast cancer cells.
AB  - Cancer multidrug resistance (MDR) is a major impediment to effective chemotherapy
      in human cancer, in which P-glycoprotein and Multidrug Resistance-Associated
      protein figure prominently. Design and exploitation of novel clinical MDR
      inhibitors is greatly hindered by a lack of understanding of drug efflux dynamics
      in drug-sensitive and resistant cells. The aim of our study was to provide a
      microelectrode method for measuring the multidrug transporter mediated efflux of
      doxorubicin as well as a corresponding data analysis method for quantifying the
      efflux kinetic parameters. We performed experiments using carbon fiber
      microelectrode to detect doxorubicin efflux from a monolayer of human breast
      cancer MCF-7 cells and derived MDR cells (MCF-7/ADR), established a material
      transport model and proposed a novel inverse method to quantitatively
      characterize the diffusion dynamics. The kinetic parameters of doxorubicin efflux
      from MCF-7 and MCF-7/ADR cells in the presence or absence of MDR inhibitors were
      estimated. Our investigations showed the average initial doxorubicin efflux rate
      of MCF-7/ADR that was 5.2 times faster than of MCF-7. After treatment by
      tetramethylpyrazine or verapamil, the drug efflux rate of the MCF-7/ADR cells was
      reduced by about half that of those without inhibitors. The novel methodology
      presented suggests new and expanded applications for computer-aided
      reconstruction of the drug efflux process, microelectrode design, and high
      throughput drug screening.

PMID- 17451884
TI  - Selenocysteine beta-lyase and methylselenol demethylase in the metabolism of Se
      methylated selenocompounds into selenide.
AB  - The lyase activity toward Se-methylated selenoamino acids and the demethylase
      activity toward methylselenol in the metabolism of selenium were characterized in
      vitro. The beta- and gamma-lyase activities toward selenomethionine (SeMet) and
      Se-methylselenocysteine (MeSeCys), respectively, were compared under exactly
      identical conditions by incubating 77Se-SeMet and 76Se-MeSeCys simultaneously in
      a liver supernatant, and then estimated by the decreases in the labeled starting
      selenoamino acids (MeSeCys and SeMet), and also by the increases in the labeled
      enzyme products (methylselenol and selenide) after oxidation to methylseleninic
      acid (MSA(IV)) and selenite, respectively, by HPLC-inductively coupled plasma
      mass spectrometry (ICP-MS). Only 76Se-MeSeCys was decreased and only 76Se
      selenite was produced, suggesting that conversion of MeSeCys to methylselenol by
      beta-lyase followed by that of methylselenol to selenide by demethylase actively
      occurred in the liver supernatant. The demethylase activity was characterized by
      incubating 77Se-methylselenol produced in situ from 77Se-MSA(IV) and glutathione
      in a partially purified enzyme preparation. It was found that demethylation takes
      place directly through an attack by a hydroxide anion on the methyl group of
      methylselenol producing selenide and methanol, selenide being detected on HPLC
      ICP-MS after oxidation to selenite, and methanol on GC-MS. It was concluded that
      beta- but not gamma-lyase activity could be detected in a liver supernatant, and
      that the resulting methylselenol product is demethylated through hydrolysis, with
      methanol and selenide being produced (MeSeCys-->CH3SeH-->HSeH + CH3OH).

PMID- 17451885
TI  - A novel extracellular EF-hand protein involved in the shell formation of pearl
      oyster.
AB  - Mollusk shell formation is a complicated and highly controlled calcium metabolism
      process. Previous studies revealed that several EF-hand calcium-binding proteins
      actively participate in the regulation of shell mineralization. In this study, we
      cloned a full-length cDNA encoding a novel extracellular EF-hand calcium-binding
      protein (named EFCBP) from the pearl oyster, Pinctada fucata, according to the EF
      hand motifs of calmodulin. Although it shares high similarity with the calmodulin
      family in its EF-hand signatures, EFCBP just has two EF-hand motifs and belongs
      to a new separate group from the other EF-hand proteins according to a
      phylogenetic analysis. EFCBP is specifically expressed in shell mineralization
      related tissues, viz. the mantle, the gill, and the hemocytes. Moreover, its
      expression responds quickly only to the shell damage, but not to the damage of
      other tissues and the infection of the lipopolysaccharides from Escherichia coli.
      These results suggest that EFCBP might be an important regulator of shell
      formation. This finding may help better understand the functions of EF-hand
      proteins on the regulation of mollusk shell formation.

PMID- 17451886
TI  - The role of nuclear receptors in pharmacokinetic drug-drug interactions in
      oncology.
AB  - Drug-drug interactions can have a major impact on treatment outcome in cancer
      patients. These patients are at high risk of such interactions, because they are
      treated with combinations of multiple cytotoxic anticancer drugs or hormonal
      agents often co-administered with prophylactic antiemetics and analgesics to
      provide palliation. Interactions between drugs can affect the pharmacokinetics of
      concomitantly administered chemotherapeutic agents. Especially, due to the
      specific properties of anticancer drugs, such as a narrow therapeutic index and
      steep dose-toxicity curve, small pharmacokinetic changes can have significant
      clinical consequences like decreased therapeutic efficacy or increased toxicity.
      An important mechanism that underlies these interactions is the induction of
      enzymes or efflux transporters involved in the biotransformation and clearance of
      anticancer drugs. Several nuclear receptors, like the pregnane X receptor (PXR),
      constitutively androstane receptor (CAR), have been shown to regulate induction.
      Activation of these receptors will lead to induction of important enzymes like
      cytochrome P450 3A4 (CYP3A4), which is involved in the biotransformation of more
      than 50% of all clinically used drugs. Therefore, concomitant administration of
      agents that activate PXR will affect the pharmacokinetics of drugs that are
      substrate for PXRs target genes, which include CYP3A4 and MDR-1. Understanding of
      the molecular mechanisms that underlie enzyme induction and the identification of
      (new) drugs involved in pharmacokinetic drug-drug interactions may contribute to
      the predictability of drug-drug interactions and eventually help to develop safer
      anticancer regimens.

PMID- 17451887
TI  - Alpha-lipoic acid may be a clinically useful therapy in interstitial cystitis.

PMID- 17451888
TI  - Inflammatory myofibroblastic tumor of the perirenal soft tissue misdiagnosed as
      renal cell carcinoma.
AB  - Inflammatory myofibroblastic tumor (IMT) of the kidney or perirenal soft tissue
      is a rare benign lesion that can mimic a malignant renal neoplasm. We describe
      the case of a 51-year-old woman that had originally been misdiagnosed as renal
      cell carcinoma in another hospital. Histologic re-evaluation of the tumor in our
      institution showed that it was in fact an IMT. Awareness of this entity is
      required for rendering the accurate diagnosis. An association with inflammatory
      infiltrate, frequent erythrocyte extravasations, edematous or myxoid stroma,
      absence of atypical mitosis, and the results of a detailed immunohistochemical
      panel might help in the differential diagnosis. Our patient is recurrence-free in
      the 18th month of post-operative follow-up.

PMID- 17451889
TI  - Biochemotherapy with immunomodulating pineal hormones other than melatonin: 5
      methoxytryptamine as a new oncostatic pineal agent.
AB  - Several experiments have demonstrated that pineal gland plays a physiological
      anticancer role. Melatonin (MLT), its most investigated hormone, is a natural
      anticancer agent. However, MLT would not be the only endocrine molecule
      responsible for the anticancer property of the pineal gland. In fact, another
      pineal indole hormone, the 5-methoxytryptamine (5-MTT), has appeared to exert in
      vitro an antitumour activity superior to that of MLT itself. Previous studies
      have already shown the therapeutic anticancer action of MLT in association with
      chemotherapy also in human neoplasms. This study was performed to evaluate the
      influence of 5-MTT at physiological doses (1 mg/day orally during light phase) on
      the efficacy of chemotherapy with cisplatin plus etoposide in advanced non-small
      cell lung cancer patients with respect to that obtained in patients treated by
      chemotherapy alone or chemotherapy plus pharmacological doses of MLT (20 mg/day
      orally during the dark phase of the day). The study included 100 patients, who
      were randomised to receive chemotherapy alone or in association with MLT or 5
      MTT. The overall response rate achieved in both patients concomitantly treated
      with MLT or 5-MTT was significantly higher with respect to that obtained in
      patients treated with chemotherapy alone. Moreover, both MLT and 5-MTT
      significantly reduced some chemotherapy-related toxicities, namely
      thrombocytopenia and neurotoxicity. This preliminary study shows that less known
      pineal hormone 5-MTT may exert at low doses the same anticancer therapeutic
      effect in association with chemotherapy, which may be obtained by pharmacological
      doses of the most investigated pineal hormone MLT.

PMID- 17451890
TI  - Contextual renewal of cocaine seeking in rats and its attenuation by the
      conditioned effects of an alternative reinforcer.
AB  - The present experiment investigated contextual renewal of cocaine seeking and
      potential methods of attenuating this renewal. Rats were first trained in one
      context to self-administer cocaine when a discriminative stimulus (tone) was
      presented. Then, the ABA Group was placed in a second context and responses in
      tone no longer produced cocaine (extinction). The AAA Group received this
      extinction in the original context. For two additional groups, responding to the
      tone was eliminated in a second context by additionally presenting food in tone
      according to a differential-reinforcement-of-other-behavior (DRO Group) schedule
      or independently of the rats' behavior on a fixed-time (FT Group) schedule.
      Renewal of responding to the tone was observed when the ABA Group was returned to
      the original context for a renewal test, but no renewal was observed in the AAA
      Group. Renewal also occurred in the DRO and FT Groups upon returning to the
      original context, but this renewal was significantly less than that of the ABA
      Group. These results suggest that response elimination techniques that are more
      active than simple extinction, such as pairing drug-related stimuli with
      alternative reinforcement, could reduce renewal of drug seeking and thereby help
      prevent relapse.

PMID- 17451892
TI  - The quantification of lipid and protein oxidation in stallion spermatozoa and
      seminal plasma: seasonal distinctions and correlations with DNA strand breaks,
      classical seminal parameters and stallion fertility.
AB  - The goal of this work was to correlate oxidative stress caused by reactive oxygen
      species (ROS) and DNA damage with classic semen parameters in spermatozoa and
      seminal plasma of fertile and subfertile stallions. Oxidation was measured in
      both lipids and proteins, using the thiobarbituric acid reactive species (TBARS)
      assay and the DNPH carbonyl groups assay, respectively. Sperm DNA damage was
      monitored using the TUNEL assay. These parameters were monitored in samples
      obtained during the breeding and the non-breeding seasons. In general, fertile
      stallions showed better classical semen parameters, and those parameters improved
      from the non-breeding to the breeding season, although an increase in sperm
      production was accompanied by a decrease in the semen quality from subfertile
      stallions in the breeding season. In terms of oxidation levels we found that
      there were clear differences whether lipids or proteins were considered. In the
      breeding season there seemed to be a tendency towards normalizing lipid oxidation
      in spermatozoa and seminal plasma, and protein oxidation in the seminal plasma,
      of both fertile and subfertile animals. Thus, differences monitored in the non
      breeding season were no longer visible. Interestingly, a higher level of protein
      oxidation was found in the sperm of fertile animals in the breeding season.
      Considering that there were positive correlations between sperm protein oxidation
      and sperm motility and vitality, these results suggests that the oxidation of
      semen proteins may be important for sperm function. On the other hand, lipid
      oxidation in the seminal plasma seemed to be a general indicator for sperm
      damage. In the non-breeding season positive correlations between lipid and
      protein oxidation levels in both sperm and seminal plasma and several defects in
      sperm function were found, but only for subfertile animals, thus suggesting that
      lipid and protein oxidation may aid in the identification of subfertile stallions
      during the non-breeding season. Levels of ROS production never seemed to result
      in compromised sperm DNA integrity, indicating that measurements were within
      physiological levels and/or that there is an efficient antioxidant activity in
      stallion sperm cells.

PMID- 17451891
TI  - Radial spoke protein 44 (human meichroacidin) is an axonemal alloantigen of sperm
      and cilia.
AB  - To identify novel sperm alloantigens relevant to immune infertility, sera from
      infertile men containing antisperm antibodies (ASA) were employed on 2-D
      immunoblots of human sperm proteins. An immunoreactive protein spot (MW: 44 kDa,
      pI: 4.5) was microsequenced and the related cDNA was cloned yielding a 309 amino
      acid sequence corresponding to a gene currently annotated in Genbank as TSGA2
      homolog (mouse) to signify 'testis specific gene A2'. In Genbank the protein
      deduced from this gene is currently named human meichroacidin, an orthologue of
      meichroacidin previously identified in mouse spermatocytes. Human TSGA2 mapped to
      chromosome 21q22.3. Human meichroacidin (hMCA) contained a single potential
      tyrosine phosphorylation site and five casein kinase phosporylation motifs. The N
      terminus contained a Membrane Occupation Recognition Nexus (MORN) motif found in
      the lipid kinase-phosphatidylinositol 4-phosphate 5-kinase (PIP5K) family and
      junctophilins. However hMCA lacked the characteristic kinase homology domain of
      PIP5K. Northern blot analysis revealed 1.5 kb hMCA transcripts in testis and
      trachea with lower levels in thyroid and spinal cord. A semi-quantitative reverse
      transcription polymerase chain reaction (RT-PCR) analysis demonstrated occurrence
      of the mRNA messages in all the ciliated tissues tested with highest levels of
      messages in testis and trachea. Western blot analysis showed the presence of hMCA
      protein in brain, thyroid and trachea at the identical mass, 44 kDa, as in human
      testis. However, this immunoreactive pattern differed from that of sperm in which
      a 38 kDa form was also evident suggesting that hMCA undergoes proteolytic
      processing. In human testis, hMCA localized to the tails of developing spermatids
      and did not localize to the nucleus of either spermatocytes or spermatids. EM
      immunocytochemistry localized hMCA within the radial spokes of the axonemal
      complex of the sperm flagellum, and immunofluorescence studies revealed h
      meichroacidin in the cilia of epithelial cells in the trachea and ependyma.
      Bioinformatic identification of orthologues of meichroacidin in several lower
      organisms including ciliates and flagellates suggest the protein plays a role in
      flagellar motility across phyla. We propose the term radial spoke protein 44 as
      an accurate designation, preferable to human meichroacidin because it denotes the
      restricted localization of the protein to the radial spokes of the axonemes of
      both sperm and cilia. Further, since the human gene is expressed in brain,
      thyroid, trachea and lung in addition to testis, we suggest that the gene name be
      changed from TSGA2 [testis specific gene A2] to radial spoke protein 44 [RSP44].

PMID- 17451893
TI  - Lower serum DHEAS levels are associated with a higher degree of physical
      disability and depressive symptoms in middle-aged to older African American
      women.
AB  - BACKGROUND: Changes in androgen levels and associations with chronic disease,
      physical and neuropsychological function and disability in women over the middle
      to later years of life are not well understood and have not been extensively
      studied in African American women. AIMS: The present cross-sectional analysis
      reports such levels and associations in community dwelling, African American
      women aged 49-65 years from St. Louis, Missouri. METHODS: A home-based physical
      examination and a health status questionnaire were administered to randomly
      sampled women. Body composition (DEXA), lower limb and hand-grip muscle strength,
      physical and neuropsychological function and disability levels were assessed.
      Blood was drawn and assayed for total testosterone (T), sex hormone-binding
      globulin (SHBG), dehydroepiandrosterone-sulfate (DHEAS), oestradiol (E2),
      adiponectin, leptin, triglycerides, glucose, C-reactive protein (CRP) and
      cytokine receptors (sIL2r, sIL6r, sTNFr1 and sTNFr2). Multiple linear regression
      modelling was used to identify the best predictors of testosterone, DHEAS and
      free androgen index (T/SHBG). RESULTS: Seventy-four percent of women were
      menopausal and a quarter of these were taking oestrogen therapy. DHEAS and E2
      declined between the ages of 49 and 65 years, whereas total T, SHBG and FAI
      remained stable. Total T and DHEAS levels were strongly correlated. In this
      population sample there were no independent associations of either total T or FAI
      with indicators of functional limitations, disability or clinically relevant
      depressive symptoms. Unlike total T and FAI, lower DHEAS levels were
      independently associated with both higher IADL scores (indicating a higher degree
      of physical disability) and higher CESD scores (indicating a higher degree of
      clinically relevant depressive symptoms). CONCLUSION: There is an age-related
      decline in serum DHEAS in African American women. Lower DHEAS levels appear to be
      associated with a higher degree of physical disability and depressive symptoms in
      this population.

PMID- 17451895
TI  - Characterization of human insulin microcrystals and their absorption enhancement
      by protease inhibitors in rat lungs.
AB  - Pulmonary route appears to be an attractive alternative as a non-invasive
      systemic delivery for peptide and protein drugs. An appropriate formulation,
      however, is important for increasing their bioavailability in lung. In this
      study, the human insulin microcrystals were produced. The particle size analysis
      and scanning electron microscopy (SEM) showed that the microcrystals were uniform
      and had a monodispersed size distribution (mean diameter = 0.95 microm) for
      pulmonary delivery. The physicochemical properties of the microcrystals developed
      were similar to those of the commercial crystalline powder in powder X-ray
      diffraction (XRD) and differential scanning calorimetry (DSC) analyses. The
      percentage of high molecular weight proteins (%HMWP), the percentage of other
      insulin related compounds (%OIRC) and the percentage of A-21 desamido insulin
      (%D) of the microcrystals were very low. In addition, the cytotoxicity of
      microcrystals developed and protease inhibitors (aprotinin, bacitracin and
      soybean-trypsin inhibitor) was investigated, and the enhancement of insulin
      absorption in the presence of these protease inhibitors at various concentrations
      was studied. The cell viability of A549 was over 80% at various concentrations of
      aprotinin and soybean-trypsin inhibitor, except for bacitracin (below 60%). The
      percent of decrease in blood glucose (D%) was 42.68+/-1.62% after intratracheal
      instillation of insulin microcrystals (5 U/kg). An enhancement of hypoglycemic
      effect with protease inhibitors was also found. Soybean-trypsin inhibitor
      (48.86+/-3.24% at 10 mg/ml; 55.78+/-0.71% at 5 mg/ml; 51.49+/-5.27% at 1 mg/ml)
      and aprotinin (52.57+/-8.78% at 10 mg/ml; 51.97+/-1.98% at 5 mg/ml; 56.90+/-3.42%
      at 1 mg/ml) were effective for absorption enhancement. These findings suggest
      that the use of insulin microcrystals and protease inhibitors would be useful to
      improve the hypoglycemic effect in pulmonary route.

PMID- 17451894
TI  - Both P-gp and MRP2 mediate transport of Lopinavir, a protease inhibitor.
AB  - Polarized epithelial non-human (canine) cell lines stably transfected with human
      or murine complementary DNA (cDNA) encoding for various efflux transporters (P
      gp/MDR1, MRP1, MRP2, and Bcrp1) were used to study transepithelial transport of
      Lopinavir (LVR) and compare results with the MDCKII-wild type cells. These
      transmembrane proteins cause multidrug resistance by decreasing the total
      intracellular accumulation of drugs. Lopinavir efflux was directional and was
      completely inhibited by MK-571, a selective MRP family inhibitor in the MDCKII
      MRP2 cell line. Similarly, LVR efflux was also inhibited by P-gp inhibitors P-gp
      4008 and GF120918 in the MDCKII-MDR1 cell line. The efflux ratios of LVR in the
      absence of any efflux inhibitors in the MDCK-wild type, MDCKII-MDR1, MDCKII-MRP1
      and MDCKII-MRP2 cell monolayers were 1.32, 4.91, 1.26 and 2.89 respectively. The
      MDCKII-MDR1 and MDCKII-MRP2 cells have significantly increased LVR efflux ratio
      relative to the parental cells due to the apically directed transport by MDR1 and
      MRP2 respectively. The efflux ratios in MRP2 and MDR1 transfected cell lines were
      close to unity in the presence of MK-571 and P-gp-4008, respectively, indicating
      that LVR efflux by MRP2 and P-gp was completely inhibited by their selective
      inhibitors. MDCKII-MRP1 cells did not exhibit a significant reduction in the LVR
      efflux relative to the parental cells, indicating that LVR is not a good
      substrate for MRP1. Transport studies across MDCKII-Bcrp1 cells indicated that
      LVR is not transported by Bcrp1 and is not a substrate for this efflux protein.
      In conclusion, this study presents direct evidence that LVR is effluxed by both P
      gp and MRP2 which may contribute to its poor oral bioavailability and limited
      penetration into the CNS.

PMID- 17451896
TI  - The influence of fluid physicochemical properties on vibrating-mesh nebulization.
AB  - In this study, the effect of fluid physicochemical properties and the vibrating
      mesh mechanism on the aerosols generated from vibrating-mesh nebulizers have been
      evaluated using fluids having a range of viscosity, surface tension and ion
      concentration. Two nebulizers were investigated: the Omron MicroAir NE-U22
      (passively vibrating) and the Aeroneb Pro (actively vibrating) mesh nebulizers.
      For both devices, the total aerosol output was generally unaffected by fluid
      properties. Increased viscosity or ion concentration resulted in a decrease in
      droplet volume median diameter (VMD) and an increase in fine particle fraction
      (FPF). Moreover, increased viscosity resulted in prolonged nebulization and
      reduced output rate, particularly for the Omron nebulizer. Both nebulizers were
      unsuitable for delivery of viscous fluids since nebulization was intermittent or
      completely ceased at >1.92cP. The presence of ions reduced variability
      particularly for the Aeroneb Pro nebulizer. No clear effect of surface tension
      was observed on the performance of nebulizers employing a vibrating-mesh
      technology. However, when viscosity was low, reduced surface tension seemed
      advantageous in shortening the nebulization time and increasing the output rate,
      but for the Omron nebulizer this also increased the droplet VMD and decreased the
      FPF. This study has shown that vibrating-mesh nebulization was highly dependent
      on fluid characteristics and nebulizer mechanism of operation.

PMID- 17451897
TI  - Behavioral recovery following sub-chronic paeoniflorin administration in the
      striatal 6-OHDA lesion rodent model of Parkinson's disease.
AB  - In the present studies, the effect of paeoniflorin (PF), one of the main
      compounds extracted from Paeoniae radix, in alleviating the neurological
      impairment following unilateral striatal 6-hydroxydopamine (6-OHDA) lesion was
      examined in Sprague-Dawley rats. Sub-chronic PF (2.5, 5 and 10 mg/kg, s.c., twice
      daily for 11 days) administration dose-dependently reduced apomorphine (APO)
      induced rotation, suggesting that PF had an ameliorative effect on the 6-OHDA
      induced neurological impairment. Notably, PF had no direct action on dopamine
      D(1) receptor or dopamine D(2) receptor indicated by the competitive binding
      experiments. These results suggest that PF, an active component of Paeoniae
      radix, might provide an opportunity to introduce a non-dopaminergic management of
      Parkinson's disease.

PMID- 17451898
TI  - Digital forensic osteology--possibilities in cooperation with the Virtopsy
      project.
AB  - The present study was carried out to check whether classic osteometric parameters
      can be determined from the 3D reconstructions of MSCT (multislice computed
      tomography) scans acquired in the context of the Virtopsy project. To this end,
      four isolated and macerated skulls were examined by six examiners. First the
      skulls were conventionally (manually) measured using 32 internationally accepted
      linear measurements. Then the skulls were scanned by the use of MSCT with slice
      thicknesses of 1.25 mm and 0.63 mm, and the 33 measurements were virtually
      determined on the digital 3D reconstructions of the skulls. The results of the
      traditional and the digital measurements were compared for each examiner to
      figure out variations. Furthermore, several parameters were measured on the
      cranium and postcranium during an autopsy and compared to the values that had
      been measured on a 3D reconstruction from a previously acquired postmortem MSCT
      scan. The results indicate that equivalent osteometric values can be obtained
      from digital 3D reconstructions from MSCT scans using a slice thickness of 1.25
      mm, and from conventional manual examinations. The measurements taken from a
      corpse during an autopsy could also be validated with the methods used for the
      digital 3D reconstructions in the context of the Virtopsy project. Future aims
      are the assessment and biostatistical evaluation in respect to sex, age and
      stature of all data sets stored in the Virtopsy project so far, as well as of
      future data sets. Furthermore, a definition of new parameters, only measurable
      with the aid of MSCT data would be conceivable.

PMID- 17451899
TI  - Relationships of plant pathogenic enterobacteria based on partial atpD, carA, and
      recA as individual and concatenated nucleotide and peptide sequences.
AB  - Relationships of the genera in the Enterobacteriaceae containing plant pathogenic
      species: Brenneria, Dickeya, Enterobacter, Erwinia, Pantoea, Pectobacterium, and
      Samsonia, were investigated by comparison of their nucleotide and peptide
      sequences of atpD, carA, recA, and the concatenated sequences. Erwinia spp. and
      Pantoea spp., with Pectobacterium cypripedii, formed a group distinct from other
      pathogenic taxa. Pectobacterium, Brenneria, Dickeya, and Samsonia formed a
      contiguous clade. Samsonia was usually concurrent with Pectobacterium. Most
      Brenneria were also close to Pectobacterium, suggesting that these three taxa
      might be better represented as a single genus. Brenneria quercina was not closely
      associated with other members of this genus and may represent a separate genus.
      The sequences representing Dickeya were distinct, further supporting the generic
      status of the taxon. Plant pathogenic Enterobacter spp. display such sequence
      variability that few definite conclusions as to their specific placement could be
      made. These data highlight the difficulty of drawing reliable and robust
      taxonomic conclusions based on comparative analysis of sequence data without some
      independent criterion to calibrate a scale for diversity.

PMID- 17451900
TI  - Functional MR imaging in the awake monkey: effects of motion on dynamic off
      resonance and processing strategies.
AB  - Functional MR imaging of the alert, behaving monkey is being used more and more
      often to detect activation patterns and guide electrophysiological research
      investigating the neural basis of behavior. Several labs have reported fMRI data
      from the awake monkey, but none of them has studied and systematically corrected
      the effects of monkeys' motion on fMRI time series. In this study, a significant
      refinement of acquisition and correction strategies is reported that can be used
      to minimize magnetic susceptibility artifacts induced by respiration and by jaw
      and body movement. Real-time acquisition of sensor signals (e.g., signals induced
      by jaw and body movement) and MR navigator data were combined to optimize fMRI
      signal-correction strategies. Within trials, the artifact-induced off-resonance
      changes were small and mainly reflected the effects of respiration; between
      trials, movements caused major changes of global frequency and shim (>20 Hz/cm).
      Several methods were used to assess the stability of the fMRI series: k-space
      analysis ('dynamic intensity and off-resonance changes in k-space', dubbed DICK
      and DORK) and image analysis using a Laplace operator and a center-of-mass
      metric. The variability between trials made it essential to correct for inter
      trial variations. On the other hand, images were sufficiently stable with our
      approach to perform fMRI evaluations on single trials before averaging of trials.
      Different motion correction strategies were compared: DORK, McFLIRT (rigid body
      model with three translations and three rotations) and 2D image alignment based
      on a center-of-mass detection (in-plane translation). The latter yielded the best
      results and proved to be fast and robust for intra- and inter-trial alignment.
      Finally, fMRI in the behaving monkey was tested for spatial and temporal
      reproducibility on a trial-to-trial basis. Highly activated voxels also displayed
      good reproducibility between trials. On average, the BOLD amplitude response to a
      short 3-s visual stimulus was close to 2%.

PMID- 17451901
TI  - Genetically controlled MRI contrast mechanisms and their prospects in systems
      neuroscience research.
AB  - Application of MRI contrast agents to neural systems research is complicated by
      the need to deliver agents past the blood-brain barrier or into cells, and the
      difficulty of targeting agents to specific brain structures or cell types. In the
      future, these barriers may be wholly or partially overcome using genetic methods
      for producing and directing MRI contrast. Here we review MRI contrast mechanisms
      that have used gene expression to manipulate MRI signal in cultured cells or in
      living animals. We discuss both fully genetic systems involving endogenous
      biosynthesis of contrast agents, and semi-genetic systems in which expressed
      proteins influence the localization or activity of exogenous contrast agents. We
      close by considering which contrast-generating mechanisms might be most suitable
      for applications in neuroscience, and we ask how genetic control machinery could
      be productively combined with existing molecular agents to enable next-generation
      neuroimaging experiments.

PMID- 17451902
TI  - Improved temporal clustering analysis method applied to whole-brain data in
      acupuncture fMRI study.
AB  - Temporal clustering analysis (TCA) has been proposed as a method for detecting
      the brain responses of a functional magnetic resonance imaging (fMRI) time series
      when the time and location of activation are completely unknown. But TCA is not
      suitable for treating the time series of the whole brain due to the existence of
      many inactive pixels. In theory, active pixels are located only in gray matter
      (GM). In this study, SPM2 was used to segment functional images into GM, white
      matter and cerebrospinal fluid, and only the pixels in GM were considered. Thus,
      most of inactive pixels are deleted, so that the sensitivity of TCA is greatly
      improved in the analysis of the whole brain. The same set of acupuncture fMRI
      data was treated using both conventional TCA and modified TCA (MTCA) for
      comparing their analytical ability. The results clearly show a significant
      improvement in the sensitivity achieved by MTCA.

PMID- 17451903
TI  - Diffusion tensor MRI to investigate dementias: a brief review.
AB  - Diffusion tensor magnetic resonance imaging (DT-MRI) is a powerful quantitative
      technique with the ability to detect in vivo microscopic characteristics and
      abnormalities of brain tissue. It has been successfully applied to a number of
      neurological conditions, such as stroke, multiple sclerosis and brain tumors,
      providing information otherwise inaccessible on the pathological substrates. DT
      MRI has also been used to study patients with cognitive decline, mainly those
      with Alzheimer's disease. Several image-analysis approaches have been employed,
      including region of interest, histogram, voxel-based analyses and DT-MRI-based
      tractography. Specific patterns of spatial distribution of tissue damage and
      correlations with neuropsychological measures have been reported. This review
      focuses on the use of DT-MRI to investigate dementias. The main clinical results
      and the different methods of image analysis will be overviewed and discussed.

PMID- 17451904
TI  - Real-time functional magnetic resonance imaging: methods and applications.
AB  - Functional magnetic resonance imaging (fMRI) has been limited by time-consuming
      data analysis and a low signal-to-noise ratio, impeding online analysis. Recent
      advances in acquisition techniques, computational power and algorithms increased
      the sensitivity and speed of fMRI significantly, making real-time analysis and
      display of fMRI data feasible. So far, most reports have focused on the technical
      aspects of real-time fMRI (rtfMRI). Here, we provide an overview of the different
      major areas of applications that became possible with rtfMRI: online analysis of
      single-subject data provides immediate quality assurance and functional
      localizers guiding the main fMRI experiment or surgical interventions. In
      teaching, rtfMRI naturally combines all essential parts of a neuroimaging
      experiment, such as experimental design, data acquisition and analysis, while
      adding a high level of interactivity. Thus, the learning of essential knowledge
      required to conduct functional imaging experiments is facilitated. rtfMRI allows
      for brain-computer interfaces (BCI) with a high spatial and temporal resolution
      and whole-brain coverage. Recent studies have shown that such BCI can be used to
      provide online feedback of the blood-oxygen-level-dependent signal and to learn
      the self-regulation of local brain activity. Preliminary evidence suggests that
      this local self-regulation can be used as a new paradigm in cognitive
      neuroscience to study brain plasticity and the functional relevance of brain
      areas, even being potentially applicable for psychophysiological treatment.

PMID- 17451905
TI  - A multimodality investigation of cerebral hemodynamics and autoregulation in
      pharmacological MRI.
AB  - Pharmacological MRI (phMRI) methods have been widely applied to assess the
      central hemodynamic response to pharmacological intervention as a surrogate for
      changes in the underlying neuronal activity. However, many psychoactive drugs can
      also affect cardiovascular parameters, including arterial blood pressure (BP).
      Abrupt changes in BP or the anesthetic agents used in preclinical phMRI may
      impair cerebral blood flow (CBF) autoregulation mechanisms, potentially
      introducing confounds in the phMRI response. Moreover, relative cerebral blood
      volume (rCBV), often measured in small-animal phMRI studies, may be sensitive to
      BP changes even in the presence of intact autoregulation. We applied laser
      Doppler flowmetry and MRI to measure changes in CBF and microvascular CBV induced
      by increasing doses of intravenous norepinephrine (NE) challenge in the halothane
      anesthetized rat. NE is a potent vasopressor that does not cross the blood-brain
      barrier and mimics the rapid BP changes typically observed with acute drug
      challenges. We found that CBF autoregulation was maintained over a BP range of 60
      120 mmHg. Under these conditions, no significant central rCBV responses were
      observed, suggesting that microvascular rCBV changes in response to abrupt
      changes in perfusion pressure are negligible within the autoregulatory range.
      Larger BP responses were accompanied by significant changes in both CBV and CBF
      that might confound the interpretation of phMRI results.

PMID- 17451906
TI  - How the NPX data format handles EEG data acquired simultaneously with fMRI.
AB  - There is a growing interest in combining EEG and (f)MRI data as they provide
      complementary information: EEG is characterized by a high temporal resolution but
      poor spatial one, while fMRI is characterized by a high spatial resolution but
      low temporal one. However, while a standard file format for storing EEG data is
      available since over a decade, it does not fulfill the needs of modern protocols
      and devices such as those involved in simultaneous EEG and fMRI recordings. The
      main reasons are the limited bit resolution, some difficulties encountered in
      handling and storing acquisition events or trace markers for off-line analyses
      and the impossibility to add some protocol-specific information that is not
      considered in the actual data formats. This, among others, hinders the release of
      free analysis software and makes it difficult to share data across different
      laboratories as every research unit develops its own tools according to its
      needs, stores data in proprietary formats and a lot of time is spent building
      software applications for converting data from one format to another. The NPX
      (NeuroPhysiological signals in eXtensible Markup Language) data format was
      defined to overcome these and other limitations, and here its main
      characteristics are reported as well as how some typical problems occurring in
      simultaneous EEG-fMRI recordings are also treated. Many tools based on the NPX
      technology can be freely downloaded, including a tool for removing artifacts
      occurring during simultaneous EEG-fMRI recordings.

PMID- 17451907
TI  - In vivo MRI reveals the dynamics of pathological changes in the brains of
      cathepsin D-deficient mice and correlates changes in manganese-enhanced MRI with
      microglial activation.
AB  - Cathepsin D (CTSD; EC 3.4.23.5) is essential for normal development and/or
      maintenance of neurons in the central nervous system: its deficiency causes a
      devastating neurological disorder with severely shortened life span in man, sheep
      and mouse. Neuropathologically, the CTSD deficiencies are characterized by
      selective neuronal degeneration, gliosis and accumulation of autofluorescent
      proteinaceous storage material in neurons. Our aim was to study the dynamics
      behind the pathological alterations occurring in the brains of CTSD-deficient
      (CTSD-/-) mice by using in vivo magnetic resonance imaging (MRI) and histology.
      In order to do this, we measured T(2) signal intensity (SI), apparent diffusion
      coefficient, area and volume of multiple brain structures from MR images acquired
      using T(2)-, T(1)- and diffusion-weighted sequences at three time points during
      disease progression. MRI revealed no differences in the brains between CTSD-/-
      and control mice at postnatal day 15+/-1 (P15+/-1), representing an initial stage
      of the disease. In the intermediate stage of the disease, P19(+/-1), SI
      alterations in the thalami of the affected mice became evident in both T(1)- and
      T(2)-weighted images. The terminal stage of the disease, P25, was characterized
      by marked alterations in the T(2) SI, apparent diffusion coefficient and volume
      of multiple brain structures in CTSD-/- mice. In addition, manganese enhanced
      high-resolution T(1)-weighted 3D sequences (MEMRI) and histological stainings
      revealed that the hyperintense signal areas in MEMRI matched perfectly with areas
      of microglial activation in the brains of CTSD-/- mice at the terminal disease
      stage. In conclusion, the SI alterations in the thalami of CTSD-/- mice preceded
      other changes, and the degenerative process was greatly enhanced at the age
      P19(+/-1), leading to severely reduced brain volume in just 6 days.

PMID- 17451908
TI  - Automated sample preparation and purification of homogenized brain tissues.
AB  - A robotic homogenized tissue sample transferring method has been developed by
      using a Packard MultiProbe II 8-tip system. It enables robotically transferring
      homogenized tissue samples from individual test tubes into a 96-well format plate
      for further sample purification and analysis. Extensive validation has been made
      to establish the accuracy and variability of this method. This automatic tissue
      sample transferring approach combined with automatic tissue homogenization, has
      significantly increased the throughput of tissue sample preparation in screening
      of drug candidates using liquid chromatography coupled with highly sensitive and
      selective tandem mass spectrometry (LC-MS/MS).

PMID- 17451909
TI  - Inappropriate dosage instructions in package inserts.
AB  - OBJECTIVE: Regardless of all efforts by the supervisory authority and the
      manufacturers to ensure that package inserts are patient-oriented, they are still
      under discussion. The survey package insert test (PAINT) aimed to examine the
      availability and comprehensibility of the information contained on five package
      inserts and five model versions for the same drugs. METHODS: A questionnaire
      containing 15 questions referring to the package insert contents was developed
      for a written survey. In a cross-over test design, each participant received an
      original package insert and a newly developed model version within an interval of
      4 weeks. RESULTS: One thousand one hundred and five participants gave
      significantly more correct answers (92.6-94.4%) to all 15 questions relating to
      the model package inserts, in comparison to the originals (74.7-85.8%). Most of
      the problems regarding the original versions were associated with the fact that
      the dosage instructions were given in active substance quantities rather than
      "tablet" or "volume", non-quantifiable phrases in the dosage instructions (e.g.
      take 1-3 times 2-4 tablets) and in the frequency of side effects (e.g. rare).
      Information regarding suitable counter measures to possible side effects, was
      also difficult to understand. CONCLUSION: Optimizing package inserts,
      particularly dosage instructions and information regarding possible side effects,
      is essential and achievable. PRACTICE IMPLICATIONS: Our recommendations are as
      follows: (1) every dose should be quantified in number of tablets or in volume;
      (2) use a dosage instruction table; (3) provide short and precise information
      only; (4) do not use non-quantifiable statements.

PMID- 17451910
TI  - The LBP patient perception scale: a new predictor of LBP episode outcomes among
      primary care patients.
AB  - OBJECTIVE: To describe a new tool designed to capture patients' perception of
      their low back pain (LBP) episodes-the patient perception scale (PPS) and test
      its ability to predict episode outcomes. METHODS: Thirty-two family physicians
      recruited 526 low back pain patients during an office visit. Physicians completed
      a short questionnaire at the index visit, which included both their assessments
      of patients' patient perception scale (PPS-doc) and contact information. Patients
      were then interviewed by telephone within 2 weeks after the index visit, with
      follow-up telephone contacts at 2, 4, 8 and 12 months. The patient perception
      scale as reported by the physician (PPS-doc) and patient (PPS-pt), each
      constituent question, and different combinations were analyzed for their ability
      to predict patient outcomes. RESULTS: Patients' responses (PPS-pt) proved
      predictive for all outcome items. PPS-doc was much less predictive. Measures of
      patient centeredness did not perform well in this study. CONCLUSION: By using a
      short scale based on the patient's perception of pain (PPS-pt), it is possible to
      predict adverse outcomes of a low back pain episode. The patient perception scale
      should be evaluated further and perhaps combined with other instruments for
      targeting care and chronicity prevention efforts in low back pain. PRACTICE
      IMPLICATIONS: The PPS-pt could potentially be used as part of the standard
      initial patient evaluation of new LBP patients, as a proxy for "yellow flags"
      (markers of psychosocial risk) where a positive score might be the equivalent to
      high-risk identification. The apparent advantage of this scale is its brevity and
      simplicity of administration. The separation, through this scale of pain episodes
      into simple and complex LBP might be a useful tool for helping direct resources
      and avoiding chronicity.

PMID- 17451911
TI  - [Upper aerodigestive tract carcinoma: therapeutic management].
AB  - Cancers of the upper aerodigestive tract cover the solid tumors of the oral
      cavity, pharynx and larynx. The principal risk factors identified are smoking and
      alcohol. Moreover, the combination of alcohol and smoking increases the relative
      risk by more than simple multiplication. The pretreatment work-up represents the
      starting point in the natural history of the patient's disease and conditions
      recovery and time course; it must be both specific and exhaustive. It leads to a
      TNM classification or staging that is a major prognostic factor and essential to
      determination of the appropriate therapy. Patients with cancer of the upper
      aerodigestive tract must receive cooperative multidisciplinary treatment.
      Conservative treatment strategies must be favored. Treatment is essentially
      surgical and radiological. Prognosis for survival is poor. For all stages and
      sites together, 5-year survival remains between 30 and 40%.

PMID- 17451913
TI  - Enhancement effect of sodium dodecyl benzene sulfonate (SDBS) and its application
      into voltammetric determination of telmisartan.
AB  - A sensitive and rapid electrochemical method was developed for the determination
      of telmisartan based on the enhancement effect of sodium dodecyl benzene
      sulfonate (SDBS). In 0.1 mol L(-1) HClO(4) and in the presence of 7.5x10(-5)mol
      L(-1) SDBS, a well-defined and sensitive oxidation peak was observed for
      telmisartan at the acetylene black (AB) paste electrode. However, the oxidation
      peak is poor-shaped and the peak current is very low in the absence of SDBS,
      suggesting that SDBS shows obvious enhancement effect for the determination of
      telmisartan. After all the experimental parameters were optimized, a sensitive
      and simple electrochemical method was developed for determining telmisartan. The
      oxidation peak current is proportional to the concentration of telmisartan over
      the range from 2.5x10(-7) to 2.0x10(-5)mol L(-1). The detection limit is 7.5x10(
      8)mol L(-1) after 2 min of accumulation. This new voltammetric method was
      successfully used to detect telmisartan in drugs.

PMID- 17451914
TI  - Influence of erythrocytes on the hepatic distribution kinetics of urea and
      thiourea.
AB  - The role of erythrocyte on the hepatic distribution kinetics of urea and thiourea
      was investigated in the in situ isolated perfused rat liver. Perfusion
      experiments were conducted using Krebs-bicarbonate buffer delivered via the
      portal vein in a single pass mode at a total flow rate of 15 ml/min. With urea,
      superimposable unimodal effluent curves were obtained in the presence and absence
      of erythrocytes, indicating that its distribution kinetics is not affected by
      erythrocytes. With thiourea, effluent curves were unimodal in the absence of
      erythrocytes but bimodal in the presence of erythrocytes. The maximum frequency
      output at the first peak increased from 0.017+/-0.002 to 0.042+/-0.006 s(-1) with
      an increase in the bolus hematocrit from 0.40 to 0.75, indicating that some
      thiourea fraction is retained by the erythrocytes on transit through the liver.
      Although the fractional output associated with the first peak was very similar
      (11.9% versus 11.5%), whether the perfusate contained unlabelled thiourea or not,
      this fraction was reduced from 17 to 5% with a decrease in the incubation time
      before injection from 30 min to 40s. However, there was no evidence for a
      capacity limitation; a 30-min period of pre-incubation of either radiolabelled
      thiourea alone or combined with a high concentration of unlabelled thiourea had
      minimal effect on effluent profiles.

PMID- 17451915
TI  - [Painful ophthalmoplegia in children: Tolosa-Hunt syndrome or ophthalmoplegic
      migraine?].
AB  - In children with painful ophthalmoplegia, the diagnosis of Tolosa-Hunt syndrome
      or of ophthalmoplegic migraine should only be considered when tumoral,
      infectious, inflammatory or vascular causes have been excluded by appropriate
      investigations. Both entities are classified as "neuralgia" by the International
      Headache Society, and seem to share a similar pathogenic mechanism. Both diseases
      have many clinical similarities with slight differences concerning pain
      characteristics or ocular associated symptoms. High resolution CT scan or
      contrast enhanced MRI can be necessary to exclude other causes of painful
      ophthalmoplegia. They can sometimes objectify an inflammatory process of the
      cavernous sinus in Tolosa-Hunt syndrome or a reversible enhancement and
      thickening of the cisternal segment of the oculomotor nerve during an
      ophthalmoplegic migraine. Pain and ophthalmoplegia quickly resolve with
      corticosteroids. Such treatment may decrease the risk of recurrence. It is
      important to follow-up these patients for a 2 years period and to repeat the
      etiologic assessment. We report here 2 cases of children with painful
      ophtalmoplegia.

PMID- 17451912
TI  - The cellular prion protein (PrP(C)): its physiological function and role in
      disease.
AB  - Prion diseases are caused by conversion of a normal cell-surface glycoprotein
      (PrP(C)) into a conformationally altered isoform (PrP(Sc)) that is infectious in
      the absence of nucleic acid. Although a great deal has been learned about PrP(Sc)
      and its role in prion propagation, much less is known about the physiological
      function of PrP(C). In this review, we will summarize some of the major proposed
      functions for PrP(C), including protection against apoptotic and oxidative
      stress, cellular uptake or binding of copper ions, transmembrane signaling,
      formation and maintenance of synapses, and adhesion to the extracellular matrix.
      We will also outline how loss or subversion of the cytoprotective or neuronal
      survival activities of PrP(C) might contribute to the pathogenesis of prion
      diseases, and how similar mechanisms are probably operative in other
      neurodegenerative disorders.

PMID- 17451916
TI  - [Transcutaneous bilirubin measurement in preterm infants].
AB  - Transcutaneous bilirubinometry is an effective screening tool for neonatal
      jaundice in full-term babies. But its accuracy is not shown yet in preterm
      infants. METHODOLOGY: We carried out a prospective study in a neonatal intensive
      care unit. The study included 47 preterm infants. From birth, a transcutaneous
      bilirubin measurement (BTc) using the BiliCheck was made on the forehead of each
      newborn every 8 h. Blood sampling for determination of total serum bilirubin (BS)
      was combined with BTc: 1) if value of BTc was higher than limits values for
      phototherapy; 2) on the second day of life and 3) 4 hours after cessation of
      phototherapy. RESULTS: Mean gestational age was 30 week and mean birth weight was
      1419 g. We studied 151 pairs of BTc and BS. Mean values obtained by BTc and BS
      were respectively 160.6+/-50 mumol/L and 190.6+/-61.4 mumol/L. A significant
      correlation between BTc and BS was found. But the limits of agreement were very
      wide. The negative predictive value (NPV) of BTc was above 90% in each group of
      gestational age. DISCUSSION: The need for phototherapy cannot be determined by
      BTc in preterm infants. But the BTc is reliable when its value is under the
      limits for phototherapy. CONCLUSION: With a very high incidence of neonatal
      jaundice (87%) in our cohort, a value of BTc under the limits for phototherapy
      has a good NPV in preterm infants.

PMID- 17451917
TI  - [Secondary right-sided diaphragmatic hernia following neonatal group B
      Streptococcal septicaemia in a preterm infant].
AB  - We report on a case of a secondary right-sided diaphragmatic hernia following
      group B streptococcal (GBS) septicaemia in a very low birth weight infant born at
      30 weeks. After initial improvement, the diagnosis of a secondary right-sided
      diaphragmatic hernia was suspected with the persistent radiological pulmonary
      right-sided image on the chest x-ray and the clinical degradation. The diagnosis
      was confirmed by ultrasonography on day 43. The postoperative course was simple.
      Persistent respiratory distress in a neonate, after a GBS septicaemia associated
      with a right pulmonary opacity on the chest x-ray, should prompt a careful
      evaluation. A secondary right-sided diaphragmatic hernia should be considered.
      Treatment is surgery, the prognosis is good in the absence of pulmonary
      hypoplasia.

PMID- 17451918
TI  - [Vein of Galen aneurysmal malformation: a neonatal case with unusual evolution].
AB  - We report on a neonatal patient case with a cerebral vascular dilation consistent
      with a vein of Galen malformation diagnosed on an antenatal doppler ultrasound
      examination. Antenatal diagnosis was confirmed by fetal MRI scan. After delivery,
      cerebral MRI scan found the same dilatation and showed no cerebral parenchymal
      damage. The infant's condition was stable and particularly there was no
      congestive cardiac failure. Before discharge at ten days of age, clinical
      examination and particularly cardiac examination was normal. At 14 days of age,
      symptoms in relation to a congestive cardiac failure appeared. Echocardiography
      showed a high output cardiac failure with no cardiac malformation. Infectious
      laboratory tests were normal. Evolution was initially favourable after digitalo
      diuretic treatment. Unfortunately, death occurred at 36 days of age due to
      intractable cardiac failure. This case highlights that, unusually, heart failure
      can occur long after the first days of life in cases of Galen vein aneurysmal
      malformation. The optimal time for vascular embolization in neonatal cases of
      Galen vein aneurysmal malformation is discussed.

PMID- 17451919
TI  - [Factor XIII deficiency in a newborn].
AB  - Factor XIII deficiency is an uncommon inherited disorder which is characterized
      by umbilical cord bleeding and an unusually high incidence of intracranial
      hemorrhage. We report here a case of Factor XIII deficiency in a child that
      presented a caput. succedaneum as the first manifestation of the disease and then
      an umbilical cord bleeding. The importance of performing a quantitative FXIII
      assay in the presence of strong clinical suspicion is strengthened because of the
      normality of the standard screening tests and the important therapeutic
      consequences.

PMID- 17451920
TI  - [Adolescent medicine or adolescent psychiatry: clearing up the
      misunderstanding?].

PMID- 17451921
TI  - Automated assessment of myocardial SPECT perfusion scintigraphy: a comparison of
      different approaches of case-based reasoning.
AB  - OBJECTIVE: This study compared the diagnostic accuracy of different approaches of
      case-based reasoning (CBR) for the assessment of coronary artery disease (CAD)
      using thallium-201 myocardial perfusion scintigraphy in comparison with coronary
      angiography. METHODS AND MATERIAL: For each scintigraphic image set, regional
      myocardial tracer uptake was obtained by polar map analysis. CBR algorithms based
      on a similarity measure were employed to identify similar scintigraphic images
      within the case library, where each case contained the scintigraphic data
      together with results of coronary angiography. The angiographic data of retrieved
      cases were then used to determine whether significant CAD was present in one of
      the major coronary arteries. Three different approaches of CBR were compared: (1)
      case retrieval based on a global comparison of polar map data (GLOB), (2) case
      retrieval based on a territorial comparison of polar map data (TER), and (3) case
      retrieval based on a comparison of a given case with eight sub-libraries
      classified according to the involvement of the three major coronary vessels using
      a group similarity measure (GROUP). Two matching algorithms the best-match
      approach and an adapted retrieving approach were combined with all three case
      retrieval methods and their influence on the diagnostic accuracy were
      investigated. RESULTS: For overall detection of significant CAD, the best-match
      approach of both TER and GROUP retrieval methods showed a higher diagnostic
      accuracy than the GLOB retrieval method (75% and 77% versus 70%, respectively).
      ROC analysis for the adapted retrieving approach showed a similar diagnostic
      accuracy for all three methods with an area under the curve of 0.79, 0.8, and 0.8
      for GLOB, TER, and GROUP, respectively. CONCLUSION: The observed improvement in
      the diagnostic accuracy by the new approaches may lead to further improvements of
      CBR systems, which have the potential to offer valuable decision support for
      human readers, especially for less experienced investigators.

PMID- 17451922
TI  - The importance of radiobiology to cancer therapy: current practice and future
      perspectives.

PMID- 17451923
TI  - Cardiovascular risk and adrenergic overdrive in the metabolic syndrome.
AB  - AIMS: This paper will review the role of the sympathetic nervous system in the
      pathogenesis of the metabolic syndrome as well as its importance as target of non
      pharmacologic and pharmacologic treatment. DATA SYNTHESIS: Several indices of
      adrenergic drive, such as plasma norepinephrine, norepinephrine spillover from
      adrenergic nerve terminals and efferent postganglionic muscle sympathetic nerve
      traffic, have all shown an increase in the different conditions clustering in
      metabolic syndrome, such as obesity, hypertension and insulin resistance state.
      This increase: 1) appears to be potentiated in the metabolic syndrome; and 2)
      contributes to a large extent at the cardiovascular structural and functional
      alterations typical of the disease. Based on this evidence, non-pharmacologic
      life-style interventions as well as drug treatment procedures used in the
      therapeutic approach to the metabolic syndrome should be aimed at exerting not
      only favourable haemodynamic and metabolic effects but also pronounced
      sympathoinhibition. CONCLUSION: The data reviewed in this paper strongly support
      the relevance of the sympathetic nervous system in the pathogenesis of the
      metabolic syndrome and the importance of the sympathomodulation as a specific aim
      of therapeutic intervention.

PMID- 17451924
TI  - Solid-state characterization and dissolution profiles of the inclusion complexes
      of omeprazole with native and chemically modified beta-cyclodextrin.
AB  - The aim of this work was to investigate the formation of the inclusion complex
      between omeprazole (OME), a benzimidazolic derivative and a methylated
      cyclodextrin, methyl-beta-cyclodextrin (MbetaCD), with an average degree of
      substitution of 0.5. Inclusion complex between OME and beta-cyclodextrin
      (betaCD), a natural cyclodextrin, was used as reference. In aqueous media,
      apparent stability constants (K(s)), which describe the extent of formation of
      the complexes, have been determined by UV spectroscopy and 1H NMR experiments.
      The stoichiometry of the complexes was found to be 1:1 mol:mol OME:cyclodextrin
      (CD) and the value of K(s) was higher for OME:MbetaCD than for OME:betaCD
      inclusion complexes. Solid binary systems of OME and CDs were prepared by
      different techniques, namely kneading, spray-drying and freeze-drying. The
      formation and physicochemical characterization of solid inclusion complexes were
      investigated by differential scanning calorimetry (DSC), Fourier transform
      infrared (FTIR), X-ray diffractometry (XRD) and scanning electron microscopy
      (SEM). The results show that freeze-drying method produces true inclusion
      complexes between OME and both CDs. In contrast, crystalline drug was detectable
      in kneaded and spray-drying products. The dissolution of OME from the binary
      systems was studied to select the most appropriate system for the development of
      a buccal drug delivery formulation. It was concluded that the preparation
      technique played an important role in the dissolution behaviour of the drug and
      the inclusion complex between OME and MbetaCD obtained by spray-drying and freeze
      drying allowed better performances.

PMID- 17451925
TI  - Development and characterisation of interactive mixtures with a fine-particulate
      mucoadhesive carrier for nasal drug delivery.
AB  - The aim of this study was to investigate whether mucoadhesive interactive
      mixtures can be created using carrier particles in a size range appropriate for
      nasal administration, i.e. 10-50 microm. We also used theoretical models to
      investigate if homogeneity measurements can be used to evaluate the formation of
      interactive mixtures containing carrier particles in this size range. Sodium
      starch glycolate (SSG) was used as carrier material and sodium salicylate (SS) as
      the model fine-particulate drug. The size ranges of SSG particles and amounts of
      SS were varied to find the smallest carrier particle size and highest amount of
      drug that still resulted in an interactive mixture. Visual inspection of the
      mixtures by scanning electron microscopy showed that interactive mixtures could
      be formed with carrier particles as small as 30 microm and containing up to 4%
      (w/w) of SS. Comparisons with theoretical models highlighted the difficulties of
      using homogeneity measurements to determine if interactive mixtures were formed.
      The measured coefficients of variation (CV) for the amount of drug in the samples
      were low and inferior mixtures were associated with only a slight increase. It
      was thus concluded that mucoadhesive interactive mixtures can be created in an
      appropriate size range for nasal administration, but that visual inspection of
      these mixtures is initially necessary to confirm the formation of an interactive
      mixture.

PMID- 17451926
TI  - Evaluation of alginate based mesalazine tablets for intestinal drug delivery.
AB  - The aim of this study was to develop the alginate based mesalazine tablets for
      intestinal delivery. Sodium alginate is a biocompatible, natural polymer with pH
      sensitive gel-forming ability. Matrix tablets were prepared with two types of
      sodium alginate of different amounts. The in vitro release characteristics of
      mesalazine from alginate tablets were compared with those of the commercial
      product (Salofalk). X-ray imaging was used to monitor the tablets throughout the
      gastrointestinal system. Although alginate tablets gave a faster release in an
      acidic medium compared with the commercial product (Salofalk), the cumulative
      amount of released drug of the optimum formulation was found to be almost the
      same as that of the commercial product at the end of 4 h. The alginate type and
      amount in the matrices played an important role in basic media. The release of
      the optimum formulation containing low viscosity alginate was found to be almost
      identical to that of the commercial product in acidic and basic media. Tablets
      were visualized to determine whether they were located in the terminal ileum or
      cecum for 3-6 h. Mesalazine-alginate matrix tablet formulations can deliver the
      drug to the small and large intestine. Thus, the alginate matrix system may be a
      promising system for the treatment of Crohn's disease involving both the ileum
      and large intestine.

PMID- 17451927
TI  - Release of naltrexone on buccal mucosa: permeation studies, histological aspects
      and matrix system design.
AB  - Transbuccal drug delivery has got several well-known advantages especially with
      respect to peroral way. Since a major limitation in buccal drug delivery could be
      the low permeability of the epithelium, the aptitude of NLX to penetrate the
      mucosal barrier was assessed. Ex vivo permeation across porcine buccal mucosa 800
      microm thick was investigated using Franz type diffusion cells and compared with
      in vitro data previously obtained by reconstituted human oral epithelium 100
      microm thick. Both fluxes (Js) and permeability coefficients (K(p)) are in
      accordance, using either buffer solution simulating saliva or natural human
      saliva. Permeation was evaluated also in presence of chemical enhancers or
      iontophoresis. No significant differences in penetration rate were observed using
      chemical enhancers; in contrast, Js and K(p) were extensively affected by
      application of electric fields. Tablets, designed for Naltrexone hydrochloride
      (NLX) administration on buccal mucosa, were developed and prepared by direct
      compression of drug loaded (56%) poly-octylcyanocrylate (poly-OCA) matrices. NLX
      is slowly discharged from buccal tablets following Higuchian kinetic.
      Histologically, no signs of flogosis ascribable to NLX and/or poly-OCA were
      observed, while cytoarchitectural changes due to iontophoresis were detected.
      Buccal tablets containing NLX may represent a potential alternative dosage form
      in addiction management.

PMID- 17451928
TI  - Characterization of the film formation of the dry coating process.
AB  - As the film formation of the dry coating process differs completely from
      conventional coating methods it is of certain interest to define a parameter like
      the minimum film formation temperature (MFT) used for aqueous dispersion based
      processes in order to describe an efficient film formation. Film formation occurs
      mainly during the curing step following the coating phase. Therefore, the film
      formation of the dry coating process was analyzed with regard to the two process
      parameters influencing film formation, namely curing temperature and time.
      Theophylline pellets were coated using the enteric polymer HPMCAS and TEC/Myvacet
      as plasticizer composition. The polymer and the plasticizer were applied to the
      pellets simultaneously, except for the beginning of the coating step when the
      plasticizer has been sprayed 30 s before powder feeding was started. The coated
      pellets were cured for five different time periods at eight different
      temperatures. Drug release was determined in 0.1 N HCl. Their surface and cross
      sectional morphologies were examined by scanning electron microscopy. The glass
      transition temperature of the obtained films as well as of the polymer
      plasticizer mixture obtained by casting a film using an organic solution of the
      coating components was determined by thermomechanical analysis. At higher curing
      temperature and/or extended curing time an enhancement of acid resistance is
      observed. The glass transition temperature of the coating mixture was determined
      to be 51.7+/-3.3 degrees C. It is close to the temperature needed for film
      formation. Enteric resistant pellets are obtained after curing for 0.75 h at 55
      degrees C. However, enteric resistance was achieved as well slightly below the
      glass transition temperature at 45 degrees C applying long curing periods of at
      least 12 h. This may be caused by the plasticizer gradient along the coat which
      is caused by spraying the plasticizer 30 s before starting powder feeding. This
      results in a higher plasticizer concentration of the inner layers of the coat
      relatively to the outer ones. Due to this film formation starts at the inner
      layers even below the glass transition temperature. As the plasticizer diffuses
      to the outer layers during curing according to the plasticizer gradient, film
      formation proceeds.

PMID- 17451929
TI  - Influence of processing parameters and formulation factors on the drug release
      from tablets powder-coated with Eudragit L 100-55.
AB  - The aim of this study was to develop a dry powder coating process for
      chlorpheniramine maleate (CPM) tablets using Eudragit L 100-55 as the delayed
      release polymer. Powder coating, a water and organic solvent-free process, was
      investigated as a method to prevent the migration of an ionizable, highly water
      soluble model drug into the polymeric film during the coating process. Eudragit L
      100-55 was pre-plasticized with triethyl citrate (TEC) using hot-melt extrusion
      at levels of 20%, 30%, and 40%, based on the polymer weight. The extrudate was
      subsequently cut into pellets and cryogenically ground into a fine powder. Talc
      was incorporated into the coating powder as an anti-tack agent. PEG 3350 was used
      as a primer for the powder coating of tablets with pre-plasticized Eudragit L 100
      55. The addition of polyethylene glycol 3350 (PEG 3350) to the pre-plasticized
      Eudragit L 100-55 was necessary to enhance the adhesion of the coating powder to
      the tablet cores. PEG 3350 also improved film formation and coalescence of the
      polymeric particles due to its plasticization effects on the acrylic polymer. For
      comparison, theophylline tablets were also coated with pre-plasticized Eudragit L
      100-55. Theophylline was selected as a less water soluble model drug. The powder
      coating process was performed in a modified laboratory scale spheronizer. The
      drug release rate was dependent both on TEC content and the coating level. The
      stability of the powder-coated CPM tablets was confirmed at 25 degrees C/60% RH
      over a storage time of 12 weeks.

PMID- 17451930
TI  - Construction demolition wastes, Waelz slag and MSWI bottom ash: a comparative
      technical analysis as material for road construction.
AB  - The objective of the study is to analyze the technical suitability of using
      secondary materials from three waste flows (construction and demolition waste
      (CDW), Waelz slag and municipal solid waste incineration (MSWI) bottom ash),
      under the regulations and standards governing the use of materials for road
      construction. A detailed technical characterization of the materials was carried
      out according to Spanish General Technical Specifications for Road Construction
      (PG3). The results show that Waelz slag can be adequate for using in granular
      structural layers, while CDW fits better as granular material in roadbeds.
      Likewise, fresh MSWI bottom ash can be used as roadbed material as long as it
      does not contain a high concentration of soluble salts. This paper also discusses
      the adequacy of using certain traditional test methods for natural soils when
      characterizing secondary materials for use as aggregates in road construction.

PMID- 17451931
TI  - Management of hazardous medical waste in Croatia.
AB  - This article provides a review of hazardous medical waste production and its
      management in Croatia. Even though Croatian regulations define all steps in the
      waste management chain, implementation of those steps is one of the country's
      greatest issues. Improper practice is evident from the point of waste production
      to final disposal. The biggest producers of hazardous medical waste are hospitals
      that do not implement existing legislation, due to the lack of education and
      funds. Information on quantities, type and flow of medical waste are inadequate,
      as is sanitary control. We propose an integrated approach to medical waste
      management based on a hierarchical structure from the point of generation to its
      disposal. Priority is given to the reduction of the amounts and potential for
      harm. Where this is not possible, management includes reduction by sorting and
      separating, pretreatment on site, safe transportation, final treatment and
      sanitary disposal. Preferred methods should be the least harmful for human health
      and the environment. Integrated medical waste management could greatly reduce
      quantities and consequently financial strains. Landfilling is the predominant
      route of disposal in Croatia, although the authors believe that incineration is
      the most appropriate method. In a country such as Croatia, a number of small
      incinerators would be the most economical solution.

PMID- 17451932
TI  - Beyond host-pathogen interactions: microbial defense strategy in the host
      environment.
AB  - Many extracellular pathogenic bacteria colonize human or animal bodies through
      evasion of the host immune system, a process called host-pathogen interaction.
      What happens when other intruders try to invade the same host and try to
      establish themselves in the same niche is largely unknown. In one well-studied
      case, Pseudomonas aeruginosa is known to secrete the protein azurin as a weapon
      against such invaders as cancers, parasites and viruses. The production of such
      weapons by pathogenic bacteria could provide important insights into how a
      pathogen responds in the post-colonization state to impede other intruders for
      its own survival. Moreover, these molecules might find use in the pharmaceutical
      industry as next-generation therapeutics.

PMID- 17451933
TI  - Ex utero intrapartum treatment procedure in a patient with arthrogryposis
      multiplex congenita, using continuous spinal anesthesia and intravenous
      nitroglycerin for uterine relaxation.
AB  - The ex utero intrapartum treatment procedure allows for the controlled management
      of a potentially life-threatening difficult airway in the newborn. General
      anesthesia has previously been reported for the management of this procedure. We
      report the use of continuous spinal anesthesia in conjunction with intravenous
      nitroglycerin for the ex utero intrapartum treatment procedure in a woman with
      arthrogryposis multiplex congenita, a rare syndrome characterized by rigid joints
      and limb contractures.

PMID- 17451934
TI  - Neuraxial anesthesia in a parturient with Leri-Weill dyschondrosteosis.

PMID- 17451935
TI  - Successful spinal blockade in a parturient with myotonia congenita.

PMID- 17451936
TI  - Ca(2+) signaling in dendritic spines.
AB  - Recent studies have revealed that Ca(2+) signals evoked by action potentials or
      by synaptic activity within individual dendritic spines are regulated at multiple
      levels. Ca(2+) influx through glutamate receptors and voltage-sensitive Ca(2+)
      channels located on spines depends on the channel subunit composition, the
      activity of kinases and phosphatases, the local membrane potential and past
      patterns of activity. Furthermore, sources of spine Ca(2+) interact nonlinearly
      such that activation of one Ca(2+) channel can enhance or depress the activity of
      others. These studies have revealed that each spine is a complex and partitioned
      Ca(2+) signaling domain capable of autonomously regulating the electrical and
      biochemical consequences of synaptic activity.

PMID- 17451937
TI  - Homeostatic signaling: the positive side of negative feedback.
AB  - Synaptic homeostasis provides a means for neurons and circuits to maintain stable
      function in the face of perturbations such as developmental or activity-dependent
      changes in synapse number or strength. These forms of plasticity are thought to
      utilize negative feedback signaling to sense some aspect of activity, compare
      this with an internal set point, and then adjust synaptic properties to keep
      activity close to this set point. However, the molecular identity of these
      signaling components has not been firmly established. Recent work suggests that
      there are likely to be multiple forms of synaptic homeostasis, mediated by
      distinct signaling pathways and with distinct expression mechanisms. These
      include presynaptic forms that depend on retrograde signaling to presynaptic
      Ca(2+) channels, and postsynaptic forms influenced by BDNF, TNFalpha and Arc
      signaling. Current challenges include matching signaling elements to their
      functions (i.e. as detectors of activity, as part of the set-point mechanism
      and/or as effectors of synaptic change), and fitting these molecular candidates
      into a unified view of the signaling pathways that underlie synaptic homeostasis.

PMID- 17451938
TI  - Monitoring the treatment efficacy of the vascular disrupting agent CA4P.
AB  - The purpose of this study was to investigate two non-invasive methods for
      determining the treatment efficacy of the vascular disrupting agent (VDA) CA4P:
      gadolinium enhanced dynamic contrast enhanced magnetic resonance imaging (DCE
      MRI) for perfusion analysis and enzyme-linked immunosorbent assay (ELISA) of
      blood samples. Candidate proteins were identified by multi-analyte profile
      analysis of plasma from KHT sarcoma-bearing C3H/HeJ mice after CA4P
      administration. Candidate proteins were further analysed by ELISA of plasma from
      treated C3H/HeJ, BALBc and C57BL6 mice. Changes in selected proteins, tumour
      perfusion and tumour necrotic fraction after CA4P treatment were then compared in
      individual animals. The cytokines KC and MCP-1 were observed to increase after
      CA4P treatment in all tested models. No correlation was found between KC or MCP-1
      levels and tumour necrosis. However, tumour perfusion correlated (r=0.89,
      p<0.00001) with CA4P treatment efficacy as measured by necrotic fraction,
      suggesting that DCE-MRI may have utility in a clinical setting.

PMID- 17451939
TI  - Functional responses and in vivo anti-tumour activity of h7C10: a humanised
      monoclonal antibody with neutralising activity against the insulin-like growth
      factor-1 (IGF-1) receptor and insulin/IGF-1 hybrid receptors.
AB  - A novel humanised monoclonal antibody (Mab, h7C10) was raised against the human
      insulin-like growth factor-1 receptor (IGF-1R); it exhibited potent inhibition of
      tumour growth in animal models. Further evaluation of its inhibitory activity at
      hybrid receptors (Hybrid-Rs) composed of the association between IGF-1R and
      insulin receptor (IR) was performed. Selective, potent and efficacious inhibition
      of [(125)I]IGF-1 binding as well as IGF-1- and IGF-2-mediated receptor
      phosphorylation was demonstrated at both IGF-1R and Hybrid-Rs, without activity
      at IR. Ligand-independent down-regulation of both IGF-1R and Hybrid-Rs was
      obtained upon long-term association with h7C10. In vivo evaluation was performed
      in a MDA-MB-231 xenograft mouse model, showing a 14-fold higher level of Hybrid
      Rs as compared to IGF-1R. A more potent anti-tumoural response was obtained for
      h7C10 as compared to Mabs targeting solely IGF-1R or Hybrid-Rs. The herewith
      described neutralising properties of h7C10 as potent inhibitor of both IGF-1R and
      Hybrid-Rs are likely to participate in its anti-tumoural activities and maybe of
      interest for therapeutic applications.

PMID- 17451940
TI  - Cytotoxic effects of 2-arylbenzofuran phytoestrogens on human cancer cells:
      modulation by adrenal and gonadal steroids.
AB  - Although 2-arylbenzofuran phytoalexins are known for decades, their anticancer
      activity has not been studied systematically. We have previously reported on the
      isolation and the estrogen receptor (ER) modulation properties of three new 2
      arylbenzofurans from Onobrychis ebenoides, ebenfuran I [2-(2,4-dihydroxyphenyl)-5
      hydroxy-6-methoxy-benzofuran], ebenfuran II [2-(2,4-dihydroxyphenyl)-3-formyl-4
      hydroxy-6-methoxy-benzofuran] and ebenfuran III [2-(2,4-dihydroxyphenyl)-3-formyl
      4-hydroxy-6-methoxy-5-(3-methyl-buten-2-yl)-benzofuran]. We now show that, while
      I and II could stimulate the proliferation of MCF-7 cells, III was inhibitory in
      a proliferation-dependent manner. III inhibited the growth of all human cancer
      cells examined, regardless of ER or multidrug resistance status. Estradiol
      rendered MCF-7 cells more sensitive to III, and this coincided with the ability
      of the hormone at concentrations > or = 0.1 nM to bind to the ER of the cells and
      stimulate their proliferation in the presence of III. Cell proliferation
      stimulating concentrations of I and II also enhanced the effect of III on MCF-7
      cells. However, dehydroepiandrosterone and dihydrotestosterone were ineffective
      in this respect. III-treated MCF-7 cells exhibited G1 phase arrest followed by
      detachment-induced cell death and/or apoptosis in the adherent fraction,
      pronounced induction of Bax and suppression of estradiol induction of Bcl-2. Our
      data indicate that the largely unexplored pool of benzofuran phytoalexins
      includes entities potentially suitable for chemoprevention and treatment of human
      cancer.

PMID- 17451941
TI  - The role of ThinPrep cytology in the evaluation of estrogen and progesterone
      receptor content of breast tumors.
AB  - INTRODUCTION: The objective of the current study was to analyze the potential
      value of immunocytochemical analysis on ThinPrep (TP)-processed smears, from fine
      needle aspiration (FNA) biopsies, of breast tumors for the determination of ER
      and PR content as compared with the immunohistochemical analysis performed on
      paraffin-embedded breast tumor specimens. PATIENTS AND METHODS: Percutaneous FNA
      biopsy of focal breast lesions in 119 female adult patients during a 31-month
      period was performed. Subsequently, these patients underwent surgical resection
      of the tumors. ER and PR status of the tumors was determined by
      immunocytochemical analysis on TP-processed smears and by immunohistochemical
      studies in paraffin-embedded sections. RESULTS: With the use of TP technique
      adequate material was observed in all cases. Sensitivity, specificity, positive
      predictive value (PPV), negative predictive value (NPV) and overall accuracy (OA)
      of the TP technique for the ER were 98.95%, 100%, 100%, 95.84% and 99.15%
      respectively. In addition, sensitivity, specificity, PPV, NPV and OA of the TP
      technique for the PR were 100%, 87.5%, 95.60%, 100% and 96.64%, respectively.
      CONCLUSIONS: ER and PR status can be evaluated in FNA material from breast
      carcinomas by using the TP technique. Sample collection and storage is simple and
      permits the assortment of the FNA sample for both morphologic diagnosis and
      ancillary studies. The accuracy of TP technique in the detection of ER and PR
      content is comparable to those of the histological evaluation, and could be of
      paramount importance for the preoperative planning of treatment.

PMID- 17451942
TI  - Non-isothermal thermogravimetric analysis of oil-palm solid wastes.
AB  - Thermal decomposition of oil-palm solid wastes, including oil-palm shell, fibre
      and kernel, was studied by thermogravimetric analysis (TGA). Effect of heating
      rate and sample particle size on the behaviour of thermogram and kinetic
      parameters were investigated. The one-step global model, two-step consecutive
      model and two-parallel reactions model were used to simulate the pyrolysis
      process of the three materials studied. The one-step global model was able to
      describe the fractional weight loss upon pyrolysis of oil-palm kernel reasonably
      well but gave a large deviation for oil-palm shell and fibre. The two-step
      consecutive model could improve the fitting for oil-palm shell and fibre, but it
      cannot account for the inflection characteristic of the thermogram. Prediction by
      the two-parallel reactions model gave the best fitting with the experimental data
      of all oil-palm wastes under all pyrolysis conditions investigated. This proposed
      model was also tested with other biomass materials and proved to be satisfactory.

PMID- 17451943
TI  - Itaconic acid production using sago starch hydrolysate by Aspergillus terreus
      TN484-M1.
AB  - Sago starch was hydrolyzed using either chemical agents, or enzymes at various pH
      and concentrations. Hydrolysis using 5000 AUN/ml (0.5%, w/v) glucoamylase
      exhibited the highest itaconic acid yield up to 0.36 g/g sago starch, whereas
      hydrolysis using nitric acid at pH 2.0 yielded 0.35 g/g sago starch. The medium
      was optimized and the composition was (g/l) 140 sago starch, 1.8 corn steep
      liquor, 1.2 MgSO(4).7H(2)O and 2.9 NH(4)NO(3). When the optimal conditions of
      hydrolysis and medium composition were applied to itaconic acid production in a 3
      l jar fermentor, the itaconic acid production was 48.2 g/l with a yield of 0.34
      g/g sago starch. This was filtered from the cultured broth and 37.1g of itaconic
      acid was recovered with a purity of 97.2%. This result showed that sago starch
      could be converted to a value-added product with only a simple pretreatment.

PMID- 17451944
TI  - Optimization of gelatine extraction from grass carp (Catenopharyngodon idella)
      fish skin by response surface methodology.
AB  - To establish the optimum gelatine extraction conditions from grass carp fish
      skin, response surface methodology (RSM) was adopted in this study. The effects
      of concentration of HCl (%, A), pre-treatment time (h, B), extraction temperature
      ( degrees C, C) and extraction time (h, D) were studied. The responses were yield
      (%) and gel strength (g). A=1.19%, B=24 h, C=52.61 degrees C and D=5.12h were
      determined as the optimum conditions while the predicted responses were 19.83%
      yield and 267 g gel strength. Gelling and melting points were 19.5 degrees C and
      26.8 degrees C, respectively. Moreover, grass carp gelatine showed high contents
      of imino acids (proline and hydroxyproline) 19.47%. RSM provided a powerful tool
      to optimize the extraction parameters and the results may be adapted for
      industrial extraction of gelatine from grass carp fish skins.

PMID- 17451945
TI  - Dehydrogenase activity in Lumbricus terrestris casts and surrounding soil
      affected by addition of different organic wastes and Zn.
AB  - A laboratory experiment was conducted to determine the effects of different
      organic wastes such as wheat straw (WS), tea production waste (TEW), tobacco
      production waste (TOW), cow manure (CM) and hazelnut husk (HH) on dehydrogenase
      activity (DHA) in casts of earthworm Lumbricus terrestris and surrounding soil
      using 5% (dry weight) application rates associated with increasing doses of Zn
      (0, 50, 100, 250, 500 and 1000 microg g(-1)). Twenty one days after treatment of
      Zn and organic wastes, the DHA analyses were carried out on collected casts and
      soil samples. In general, all organic waste treatments influenced the DHA, the
      contents of organic C, N and available Zn in earthworm L. terrestris casts and
      the surrounding soil in comparison with the control. DHA in casts exceeded that
      in the surrounding soil without Zn additions. After Zn application of 50 microg
      Zn g(-1) in all organic waste treatments and the control, the DHA level in casts
      and surrounding soil increased significantly. It decreased by application rates
      of 100, 250, 500 and 1000 microg Zn g(-1) consecutively in all organic waste
      applications. The addition of wastes with low C/N ratio and high Zn content (TEW,
      TOW, CM) inhibited the DHA in both cast and surrounding soil.

PMID- 17451946
TI  - Composting potential of different inoculum sources in the modified SEBAC system
      treatment of municipal solid wastes.
AB  - The aim of the work described here was to analyse the biomethanization process
      for three types of organic fraction of municipal solid waste (OFMSW) using two
      different inoculum sources in a sequential leach-bed anaerobic reactor under
      thermophilic (55 degrees C) and dry conditions (20%TS). The OFMSWs studied were:
      separately collected food waste (SC_OFMSW) from restaurants, synthetic waste
      (ST_OFMSW) and mechanically selected municipal waste (MS_OFMSW). The inoculum
      studied were digested mesophilic sludge (SLUDGE) and digested SC_OFMSW. The
      results show that SLUDGE gave the best performance and this was therefore
      selected for the rest of the experiments. Three assays were performed to analyse
      the biomethanization processes of three types of organic waste. The results
      suggest that all three wastes give rise to an acclimation stage with
      acidogenic/acetogenic activity between days 5 and 20-30 and a stabilization phase
      associated with methanogenic activity. In conclusion, a mixture of OFMSW
      (regardless of its origin) and SWINE arranged in layers in the reactor, as well
      as SLUDGE used with an inoculum source, enhanced the fast start up phase of a
      modified sequential leach-bed system under dry thermophilic conditions.

PMID- 17451947
TI  - Kinetics of organic removal in fixed-bed aerobic biological reactor.
AB  - The process kinetics of a lab-scale upflow aerobic immobilized biomass (UAIB)
      reactor using simulated sugar-manufacturing wastewater as feed was investigated.
      The experimental unit consisted of a 22l reactor filled with high porosity pumice
      stone. The UAIB reactor was tested under different organic loads and different
      hydraulic retention times (HRT) and the substrate loading removal rate was
      compared with prediction of Stover-Kincannon model, second-order model and the
      first order substrate removal model. After obtaining steady-state conditions,
      organic loading rate was increased from 750 to 4500 g COD/m(3) day to resemble
      wastewater from sugar production lines, and hydraulic retention time was
      decreased from 1 to 0.5 days, stepwise. Nine different operational conditions
      were applied changing these two parameters in a certain program. As a result of
      the calculations, Stover-Kincannon model and second-order model known as "Grau"
      model were found to be the most appropriate models for this reactor. Stover
      Kincannon model and Grau second-order model gave high correlation coefficients,
      which were 99.7% and 99.4%, respectively. Therefore, these models could be used
      in predicting the behavior or design of the UAIB reactors.

PMID- 17451948
TI  - Metal accumulation and growth performance of Phaseolus vulgaris grown in fly ash
      amended soil.
AB  - Phytoextraction of heavy metals from fly ash (FA) contaminated soil was evaluated
      using Phaseolus vulgaris var. T55. The results showed that electrical
      conductivity (EC), cation exchange capacity (CEC), organic carbon (OC) and
      organic matter (OM) of different amendments decreased with the addition of FA in
      the soil. The level of diethylene triaminepenta acetic acid (DTPA) extractable
      metals increased with increase in FA amendments up to 25%. However, Cr was found
      below detection limit in both the amendments. The metal accumulation in the plant
      tissues was found in the order of Fe>Zn>Mn>Co>Ni>Pb>Cu>Cd at 25% FA. Accumulation
      of Fe, Mn, Ni, Cu and Co was found more in the roots while Zn, Pb and Cd were
      more in the aerial parts.

PMID- 17451949
TI  - Discovery and SAR development of thienopyridones: a class of small molecule AMPK
      activators.
AB  - AMP-activated protein kinase (AMPK) is well established as a sensor and regulator
      of intracellular and whole-body energy metabolism. A high-throughput screen was
      performed in order to identify chemotypes that are bound by AMPK. A novel
      thienopyridone compound (1) was identified and subsequently optimized. The
      structure-activity relationships that emerged from this effort are described.

PMID- 17451950
TI  - Derivatives of oxoisoaporphine alkaloids: a novel class of selective
      acetylcholinesterase inhibitors.
AB  - A series of 9-aminoalkanamido-1-azabenzanthrones derviatives (3a-i Ar
      NHCO(CH(2))(n)NR(1)R(2)) and their quaternary methiodide salts (4a-g Ar
      NHCO(CH(2))(n)N(+)(CH(3))R(1)R(2)I(-)) were designed and synthesized as
      acetylcholinesterase (AChE) or butyrylcholinesterase (BuChE) inhibitors. The
      synthetic compounds exhibited high AChE inhibitory activity with IC(50) values in
      the nanomolar range and high selectivity for AChE over BuChE (45- to 1980-fold).
      The structure-activity relationships (SARs) were discussed.

PMID- 17451951
TI  - Heterocyclic substituted cantharidin and norcantharidin analogues--synthesis,
      protein phosphatase (1 and 2A) inhibition, and anti-cancer activity.
AB  - Norcantharidin (3) is a potent PP1 (IC(50)=9.0+/-1.4 microM) and PP2A
      (IC(50)=3.0+/-0.4 microM) inhibitor with 3-fold PP2A selectivity and induces
      growth inhibition (GI(50) approximately 45 microM) across a range of human cancer
      cell lines including those of colorectal (HT29, SW480), breast (MCF-7), ovarian
      (A2780), lung (H460), skin (A431), prostate (DU145), neuroblastoma (BE2-C), and
      glioblastoma (SJ-G2) origin. Until now limited modifications to the parent
      compound have been tolerated. Surprisingly, simple heterocyclic half-acid
      norcantharidin analogues are more active than the original lead compound, with
      the morphilino-substituted (9) being a more potent (IC(50)=2.8+/-0.10 microM) and
      selective (4.6-fold) PP2A inhibitor with greater in vitro cytotoxicity (GI(50)
      approximately 9.6 microM) relative to norcantharidin. The analogous
      thiomorpholine-substituted (10) displays increased PP1 inhibition (IC(50)=3.2+/-0
      microM) and reduced PP2A inhibition (IC(50)=5.1+/-0.41 microM), to
      norcantharidin. Synthesis of the analogous cantharidin analogue (19) with
      incorporation of the amine nitrogen into the heterocycle further increases PP1
      (IC(50)=5.9+/-2.2 microM) and PP2A (IC(50)=0.79+/-0.1 microM) inhibition and cell
      cytotoxicity (GI(50) approximately 3.3 microM). These analogues represent the
      most potent cantharidin analogues thus reported.

PMID- 17451952
TI  - Synthesis and local anesthetic activity of fluoro-substituted imipramine and its
      analogues.
AB  - A series of fluoro-substituted imipramines and its analogues, 6a-6e, were
      synthesized and evaluated for their in vitro local anesthetic activity. Compound
      6b was found to have potency, onset, and duration of action comparable to those
      of lidocaine (lidocaine hydrochloride, CAS:6108-05-0). Dissociation constants
      (pK(a)) of these compounds have been determined to be 7.6-7.9.

PMID- 17451953
TI  - N-(3-Triethoxysilylpropyl)-4-(N'-maleimidylmethyl)cyclohexanamide (TPMC): a
      heterobifunctional reagent for immobilization of oligonucleotides on glass
      surface.
AB  - A new heterobifunctional reagent, namely, N-(3-triethoxysilylpropyl)-4-(N'
      maleimidylmethyl)cyclohexanamide (TPMC) was developed and its potentiality for
      fixing of thiol (-SH) modified oligonucleotides were tested. The covalent
      attachment of oligonucleotides with the reagent was achieved through its
      maleimide functionality at one end via stable thioether linkage while the other
      end bearing triethoxysilyl functionality has been utilized for coupling with the
      virgin glass surface with simplified methodologies. Immobilization of
      oligonucleotides was achieved by two alternating ways. The PATH-1 involves
      formation of conjugate of reagent and SH-modified oligonucleotides through
      thioether linkage and was subsequently immobilized on unmodified glass surface
      through triethoxysilyl group and alternatively, PATH-2 involves reaction of
      reagent first with unmodified glass surface to get maleimide functionality on the
      surface and then the SH-modified oligonucleotides were immobilized via thioether
      linkage. The specificity of immobilization was tested by hybridization study with
      complementary fluorescein labeled oligonucleotide strand.

PMID- 17451954
TI  - Scaffold hopping in the rational design of novel HIV-1 non-nucleoside reverse
      transcriptase inhibitors.
AB  - High-throughput screening hit 1 was identified as a potent, broad-spectrum, non
      nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 replication. Analysis
      of the bound conformation of analogs of this inhibitor via molecular modeling and
      NMR contributed to the design of novel tertiary amide, carbamate, and
      thiocarbamate based NNRTIs.

PMID- 17451955
TI  - "About a cupful"--a prospective study into accuracy of volume estimation by
      medical and nursing staff.
AB  - In this prospective study, medical and nursing health care professionals were
      asked to visually estimate various fluid volumes. The aims were to assess overall
      accuracy, and to identify factors that caused error. The effects of fluid volume,
      colour and clinical experience were analysed. 152 doctors and nurses were shown a
      selection of containers filled with five different volumes of fluid, each
      presented in three different colours. Subjects recorded their estimates of volume
      by filling in a questionnaire. There was considerable variation in accuracy
      between subjects. Very large standard deviations were noted, and some subjects
      were found to over-report, to a maximum of 700%. Nurses were more accurate than
      doctors (p=0.0003). Nurses' accuracy was influenced by fluid colour but not
      volume, whereas the opposite was true for doctors. Doctors with more than 20
      years' clinical experience significantly overestimated volumes compared to their
      younger colleagues. This effect was not seen with the nursing group. We conclude
      that visual estimation is unreliable, and recommend against using visual
      estimation in clinical practice.

PMID- 17451956
TI  - The lived experience of working in a mortuary.
AB  - A four year action research study was undertaken in an attempt to foster change
      in the current management of sudden deaths in the Accident and Emergency
      Departments in South Africa. During the phase of interviewing bereaved families
      and health professionals it became apparent that there was a need to involve
      mortuary staff as victims of sudden deaths have to undergo an autopsy. The
      researcher chose an interpretive hermeneutic phenomenological research approach
      to explore the lived experience of working in a mortuary. The mortuary is a place
      of mystery, sadness, grief or repulsion and we all hope, while we are alive, we
      will never need to visit. For families who have lost a loved one to a sudden
      death, this becomes a reality. Working in a mortuary is an extremely stressful
      experience which is made worse in South Africa due to the large number of people
      dying sudden violent deaths due to trauma. The themes which emerged from the
      interviews with mortuary staff were; secondary trauma for families, delays by
      health professionals and dehumanised mortuary staff. There is a need for a change
      in the way bereaved families are being managed as well as revision of the
      environment for the staff working in mortuaries.

PMID- 17451957
TI  - Congenital disorder of glycosylation type 1a: three siblings with a mild
      neurological phenotype.
AB  - We report 3 siblings (1 male and 2 female) recently diagnosed with congenital
      disorder of glycosylation type Ia (CDG-Ia) in their mid-20s. They experience mild
      mental retardation but manage to function independently in society. Their
      professions are library assistant, professional artistic painter and secretarial
      work. All three siblings have cerebellar hypoplasia and ataxia, but are able to
      ambulate easily. Two of the siblings have required strabismus surgical repairs.
      All have antithrombin III deficiency, osteoporosis, and mild dysmorphic features.
      Hypergonadotrophic hypogonadism was a feature of the two female siblings. A type
      1 sialotransferrin pattern and phosphomannomutase (PMM) deficiency have been
      demonstrated. They are compound heterozygotes for R141H and L32R mutations in the
      PMM2 gene. While there is clinical heterogeneity in CDG-Ia, we believe that our
      patients are among the mildest of intellectually affected CDG-Ia patients
      reported to date.

PMID- 17451958
TI  - Loading and gait symmetry during level and stair walking in asymptomatic subjects
      with knee osteoarthritis: importance of quadriceps femoris in reducing impact
      force during heel strike?
AB  - Repetitive impulsive forces during walking are claimed to result in joint
      osteoarthritis (OA). The aim of this study was to investigate impact loading and
      gait symmetry during level and stair walking in asymptomatic elderly subjects
      with knee OA. It was hypothesised that pre-activity of the quadriceps femoris
      muscle (QF) would be an important factor reducing impulsive loading when walking
      on level ground. Subjects [21 female, six men, 66.2 (7.6) years] were studied.
      The subjects had no knee pain or diminished functional capacity, but showed
      radiographically light or moderate bilateral knee OA changes. Ground reaction
      forces (GRFs), plantar pressure distribution, muscle activation pattern [vastus
      medialis (VM), vastus lateralis, biceps femoris and gastrocnemius medialis] and
      asymmetry during level walking and stair walking were evaluated. Almost 20% of
      subjects had a distinct heel-strike transient at maximal speed with lower pre
      activity of VM (P<0.05). The most forceful maximum vertical GRF in the braking
      phase occurred in stair descent [1.52 (0.21) BW]. This was 32.5% (P<0.001) higher
      than seen when walking on the level at normal speed. The loading rate of stair
      descent [10.87 (2.96) BW/s] was significantly stronger (P<0.05) than in level
      walking at normal speed [8.55 (1.93) BW/s]. There was no asymmetry in kinematic
      or kinetic variables in level walking. However, asymmetry increased during stair
      walking. The control of quadriceps femoris prior to heel-strike is possibly an
      important factor that reduces impulsive loading during walking in asymptomatic OA
      subjects. Stair walking is a demanding motor task and the musculoskeletal system
      is loaded more during stair descent than level walking at normal speed.

PMID- 17451959
TI  - Probing the receptor interactions of an H5 avian influenza virus using a
      baculovirus expression system and functionalised poly(acrylic acid) ligands.
AB  - Influenza viruses attach to host cells by binding to terminal sialic acid
      (Neu5Ac) on glycoproteins or glycolipids. Both the linkage of Neu5Ac and the
      identity of other carbohydrates within the oligosaccharide are thought to play
      roles in restricting the host range of the virus. In this study, the receptor
      specificity of an H5 avian influenza virus haemagglutinin protein that has
      recently infected man (influenza strain A/Vietnam/1194/04) has been probed using
      carbohydrate functionalised poly(acrylic acid) polymers. A baculovirus expression
      system that allows facile and safe analysis of the Neu5Ac binding specificity of
      mutants of H5 HA engineered at sites that are predicted to effect a switch in
      host range has also been developed.

PMID- 17451960
TI  - Synthesis and glycogen phosphorylase inhibitor activity of 2,3
      dihydrobenzo[1,4]dioxin derivatives.
AB  - Novel 5-benzyl and 5-benzylidene-thiazolidine-2,4-diones carrying 2,3
      dihydrobenzo[1,4]dioxin pharmacophore were synthesized and their glycogen
      phosphorylase inhibitor activity was also studied.

PMID- 17451961
TI  - Assessing potency of c-Jun N-terminal kinase 3 (JNK3) inhibitors using 2D
      molecular descriptors and binary QSAR methodology.
AB  - JNK3 signaling pathway is gaining interest due to its involvement in many
      neurological disorders. The purpose of this study was to explore for the first
      time the use of a large and diverse dataset in combination with binary QSAR
      methodology for predicting JNK3 activity class. Data were extracted from Aureus
      Pharma' AurSCOPE Kinase knowledge database and active or inactive classes were
      assigned to ligands based on IC50 biological activity. Two sets of 2D molecular
      descriptors (P_VSA and BCUT) were used to build models using different biological
      activity thresholds. The design of the models was preceded by the evaluation of
      the chemical space covered by the datasets and an assessment of its chemical
      diversity. The best model was found using a 100 nM IC50 threshold with surface
      based P_VSA descriptors. This binary QSAR model reached an overall accuracy of
      98% and a leave-one-out cross-validated accuracy of 94%. Most relevant
      descriptors were found to encode size and hydrophobic interactions. These derived
      models can be useful for screening chemical libraries in the search for new JNK3
      inhibitors.

PMID- 17451962
TI  - Structure-based design, synthesis and preliminary evaluation of selective
      inhibitors of dihydrofolate reductase from Mycobacterium tuberculosis.
AB  - Tuberculosis is an increasing threat, owing to the spread of AIDS and to the
      development of resistance of the causative organism, Mycobacterium tuberculosis,
      to the currently available drugs. Dihydrofolate reductase (DHFR) is an important
      enzyme of the folate cycle; inhibition of DHFR inhibits growth and causes cell
      death. The crystal structure of M. tuberculosis DHFR revealed a glycerol tightly
      bound close to the binding site for the substrate dihydrofolate; this glycerol
      binding motif is absent from the human enzyme. A series of pyrimidine-2,4
      diamines was designed with a two-carbon tether between a glycerol-mimicking triol
      and the 6-position of the heterocycle; these compounds also carried aryl
      substituents at the 5-position. These, their diastereoisomers, analogues lacking
      two hydroxy groups and analogues lacking the two-carbon spacing linker were
      synthesised by acylation of the anions derived from phenylacetonitriles with
      ethyl (4S,5R)-4-benzyloxymethyl-2,2-dimethyl-1,3-dioxolane-4-propanoate, ethyl
      (4S,5S)-4-benzyloxymethyl-2,2-dimethyl-1,3-dioxolane-4-propanoate,
      tetrahydrooxepin-2-one and 2,3-O-isopropylidene-d-erythronolactone, respectively,
      to give the corresponding alpha-acylphenylacetonitriles. Formation of the methyl
      enol ethers, condensation with guanidine and deprotection gave the pyrimidine-2,4
      diamines. Preliminary assay of the abilities of these compounds to inhibit the
      growth of TB5 Saccharomyces cerevisiae carrying the DHFR genes from M.
      tuberculosis, human and yeast indicated that 5-phenyl-6-((3R,4S)-3,4,5
      trihydroxypentyl)pyrimidine-2,4-diamine selectively inhibited M. tuberculosis
      DHFR and had little effect on the human or yeast enzymes.

PMID- 17451963
TI  - Radiolabeling of multimeric neurotensin(8-13) analogs with the short-lived
      positron emitter fluorine-18.
AB  - Three methods for (18)F-labeling of dimeric and tetrameric neurotensin(8-13)
      derivatives were evaluated with respect to the labeling yield and the required
      peptide amounts. Labeling using N-succinimidyl-4-[(18)F]fluorobenzoate
      ([(18)F]SFB) gave low radiochemical yield for the dimeric peptides. Coupling of
      the tetramer with [(18)F]SFB was not successful. High yields were obtained for
      labeling of the aminooxy-functionalized neurotensin(8-13) dimer using 4
      [(18)F]fluorobenzaldehyde ([(18)F]FBA) whilst coupling of the corresponding
      tetramer gave only low yields. Labeling of sulfydryl-functionalized neurotensin(8
      13) derivatives using the maleinimide 4-[(18)F]fluorobenzaldehyde-O-[6-(2,5-dioxo
      2,5-dihydro-pyrrol-1-yl)-hexyl]-oxime ([(18)F]FBAM) resulted in high
      radiochemical yields for both, the dimer and the tetramer. Therefore, [(18)F]FBAM
      seems to be the most suitable (18)F-labeling agent for multivalent neurotensin(8
      13) derivatives.

PMID- 17451965
TI  - Immune status evaluation of patients with chronic heart failure.
AB  - Chronic heart failure (CHF) may be considered a state of immune activation and
      persistent inflammation expressed by increased circulating levels of pro- and
      anti-inflammatory cytokines. The purpose of the study was to investigate the
      immune status in patients with CHF compared to normal individuals. We measured
      serum cytokine levels as well as cytokine production after ex vivo LPS
      stimulation of whole blood taken from 14 patients with CHF and 14 healthy
      volunteers. We used 500 pg/ml of LPS for an incubation period of 4h to stimulate
      100 microL of whole blood. Patients with CHF had significantly higher levels of
      TNF-RI, and TNF-RII in serum compared to normal individuals. TNF-alpha, IL-6, and
      IL-10 did not differ significantly. After LPS stimulation, patients with CHF had
      significantly higher levels of TNF-alpha and IL-10, and significantly lower IL-6
      levels compared to normal individuals. TNF-alpha receptors did not differ
      significantly. Patients with CHF may be found in a pro- as well as an anti
      inflammatory state. They also do not develop endotoxin tolerance in an ex vivo
      laboratory model using whole blood stimulated with LPS. They may have increased
      TNF-alpha and IL-10 production after LPS stimulation of whole blood, which may
      contribute to a worsening of heart function, more severe disease presentation and
      a worse outcome during infections.

PMID- 17451966
TI  - Characterization of murine interferon-alpha 12 (MuIFN-alpha12): biological
      activities and gene expression.
AB  - Interferon alpha (IFN-alpha) belongs to the type I interferon family and consists
      of multiple subtypes in many species. In the mouse, there are at least 14 IFN
      alpha genes and 3 IFN-alpha pseudogenes, the most recently identified of which
      are murine interferon-alpha 12 (MuIFN-alpha12), MuIFN-alpha13 and MuIFN-alpha14.
      To further study the biological activities of MuIFN-alpha12, we have produced a
      recombinant MuIFN-alpha12 (rMuIFN-alpha12) protein using COS-1 cells. rMuIFN
      alpha12 was found to inhibit the growth of murine myeloid leukemia JCS cells.
      Flow cytofluorometric analysis with propidium iodide staining showed that the
      growth inhibitory activity of rMuIFN-alpha12 may be caused by the induction of
      apoptosis. Flow cytofluorometric analysis also revealed that rMuIFN-alpha12 was
      able to up-regulate the expression of MHC-I on both JCS cells and primary
      macrophages. Functional studies indicated that a MuIFN-alpha12 transgene could
      induce an anti-viral state in L929 cells against Influenza A virus. Moreover,
      expression of MuIFN-alpha12 was not detectable by RT-PCR in untreated, Influenza
      A virus infected, polyI:polyC induced L929 cells, or in a wide range of normal
      murine tissues. Taken together, this data shows that MuIFN-alpha12 is a protein
      with all the biological traits of a type I IFN.

PMID- 17451964
TI  - Human immunodeficiency virus type-1 protein Tat induces tumor necrosis factor
      alpha-mediated neurotoxicity.
AB  - HIV-1 infection causes, with increasing prevalence, neurological disorders
      characterized in part by neuronal cell death. The HIV-1 protein Tat has been
      shown to be directly and indirectly neurotoxic. Here, we tested the hypothesis
      that a non-neurotoxic epitope of Tat can, through actions on immune cells,
      increase neuronal cell death. Tat(1-72) and a mutant Tat(1-72) lacking the
      neurotoxic epitope (Tat(Delta31-61)) concentration-dependently and markedly
      increased TNF-alpha production in macrophage-like differentiated human U937 and
      THP-1 cells, in mouse peritoneal macrophages and in mouse brain microglia. Tat(1
      72) was but Tat(Delta31-61) was not neurotoxic when applied directly to neurons.
      Supernatants from U937 cells treated with either Tat(1-72) or Tat(Delta31-61)
      were neurotoxic and their immunoneutralization with an anti-TNF-alpha antibody
      decreased Tat(1-72)- and Tat(Delta31-61)-induced neurotoxicity. Together, these
      results demonstrate that the neurotoxic epitope of Tat(1-72) is different from
      the epitope that is indirectly neurotoxic following production of TNF-alpha from
      immune cells, and suggest that therapeutic interventions against TNF-alpha might
      be beneficial against HIV-1 associated neurological disorders.

PMID- 17451967
TI  - High level expression of His-tagged colicin 5 in E. coli and characterization of
      its narrow-spectrum bactericidal activity and pore-forming action.
AB  - Since antibiotics with a broad spectrum of activity would select for resistance
      among the normal flora, colicins having a narrow spectrum of activity can
      potentially be developed as novel antibiotics. Colicin-based bactericidal
      proteins with modified spectra of activity might also be developed by further
      gene fusion or gene modification. To achieve these goals, it is necessary to
      first build an efficient system to produce large amounts of colicin. In the
      presence of an immunity gene, we successfully constructed an expression vector
      pQE30-cfa-cfi producing high levels of His-tagged colicin 5 (60-80 mg/L). We
      found that the purified His-tagged colicin 5 possesses narrow-spectrum
      bactericidal activity against nonimmune Escherichia coli cells. It is highly
      toxic to sensitive E. coli cells at a low concentration of 0.01 microg/ml, while
      it is nontoxic to other tested gram-negative bacteria, gram-positive bacteria and
      yeast at a high concentration of 1000 microg/ml. His-tagged colicin 5 kills
      sensitive cells by permeabilizing their cell membranes. It is not hemolytic to
      rabbit erythrocytes and has no obvious cytotoxicity to other nucleated mammalian
      cells at a high concentration of 500 microg/ml. The His-tagged colicin 5 is
      similar to wild-type colicin 5 in spectrum and bactericidal activity against E.
      coli. It is a potential novel antibiotic particularly for treating human and
      animal infections caused by pathogenic E. coli. Besides producing high level of
      colicin 5, the highly efficient expression vector constructed here might also be
      a useful tool to develop colicin-based artificial bactericidal proteins.

PMID- 17451968
TI  - Cloning, expression and immunogenicty analysis of five outer membrane proteins of
      Vibrio parahaemolyticus zj2003.
AB  - Genes of five outer membrane proteins of Vibrio parahaemolyticus zj2003,
      including OmpW, OmpV, OmpK, OmpU and TolC, were cloned and expressed as N
      terminal His(6)-tagged proteins in Escherichia coli. The recombinant fusion
      proteins were purified with nickel chelate affinity chromatography. To analyze
      the immunogenicity of these proteins, large yellow croaker (Pseudosciaena crocea)
      were immunized by intraperitoneal injection. Antibody response was assessed by
      method of enzyme-linked immunosorbent assay. Titres to all five recombinant
      proteins increased during 4 to 8 weeks post immunization, within the range of log
      2 values of 5.75 to 10.8. Recorded relative survival percent (RPS) of the
      vaccinated groups varied from 80% to 90%, while 10 fish in control group all
      died. Western blot tests were undertaken with the serum of survival fish after
      experimental infection. Except for recombinant TolC, the other four recombinant
      proteins were recognized by the serum. It is indicated that four outer membrane
      proteins of V. parahaemolyticus zj2003, including OmpW, OmpV, OmpU and OmpK, are
      immunogenic during in vivo infection, which would be of some significance in
      developing efficient vaccine in aquaculture. This is the first report of
      successful vaccination against V. parahaemolyticus with purified recombinant
      outer membrane proteins.

PMID- 17451969
TI  - Supplementary note on "A spiking neuron model of cortical broadcast and
      competition".

PMID- 17451970
TI  - On the irrationality of emotion and the rationality of awareness.
AB  - It is argued that one answer to the question of the rationality of emotion hinges
      on the different roles in action selection played by emotions when one is aware
      of them versus when one is not aware of them (awareness being indexed by the
      ability to report one's emotion). When unaware of one's emotions, they are: (a)
      not able to enter into one's deliberations about what to do, and (b) more likely
      to be automatically acted out. This is a problem for rationality because (partly
      due to the logic of signal detection theory) emotional action urges are often
      "false positives". In contrast, awareness of emotions crucially allows emotional
      responses to be inhibited: such inhibition is necessary for truly rational action
      selection. Furthermore, awareness enables Reflective Revision--the modification
      of one's theories and action plans as a result of awareness of inconsistencies
      between theories and data, and action plans and goals.

PMID- 17451971
TI  - Role of the basal ganglia and frontal cortex in selecting and producing
      internally guided force pulses.
AB  - The basal ganglia comprise a crucial circuit involved in force production and
      force selection, but the specific role of each nucleus to the production of force
      pulses and the selection of pulses of different force amplitudes remains unknown.
      We conducted an fMRI study in which participants produced force using a precision
      grip while (a) holding a steady-state force, (b) performing a series of force
      pulses with similar amplitude, and (c) selecting force pulses of different
      amplitude. Region of interest analyses were conducted in the basal ganglia and
      frontal cortex to compare percent signal change during force pulse versus steady
      state force production and compare force amplitude selection to force production
      when selection of force amplitude was not present. There were three novel
      findings in the basal ganglia. First, the caudate nucleus increased activation
      during the selection of different force amplitudes when compared to producing a
      series of similar force pulses. Second, GPi, STN, and posterior putamen increased
      activation during the production of similar force amplitudes when compared to
      holding a steady-state force, and maintained similar activation during the
      production of different force amplitudes in which force selection was required.
      Third, GPe and anterior putamen had increased activation during the production of
      similar force pulses and further increased activation during the selection of
      different force pulses. These findings suggest that anterior basal ganglia nuclei
      are involved in selecting the amplitude of force contractions and posterior basal
      ganglia nuclei regulate basic aspects of dynamic force pulse production.

PMID- 17451972
TI  - Dissociating recollection from familiarity: electrophysiological evidence that
      familiarity for faces is associated with a posterior old/new effect.
AB  - In recognition memory research, a tension exists between dual-process and single
      process models of episodic retrieval. Dual-process models propose that
      'familiarity' assessment and the 'recollection' of contextual information are
      independent processes, while single-process models claim that one common process
      supports retrieval. Event-related potentials (ERPs) have been used to show
      dissociations between the mid frontal and the left parietal ERP old/new effects,
      which have been associated with familiarity and recollection, respectively. While
      much ERP evidence favours dual-process theory, Yovel and Paller [Yovel, G.,
      Paller, K.A., 2004. The neural basis of the butcher-on-the-bus phenomenon: when a
      face seems familiar but is not remembered. NeuroImage 21, 789-800] used faces as
      retrieval cues to demonstrate that posterior old/new effects index both
      familiarity and recollection, a finding consistent with single-process models.
      Here we present evidence supporting Yovel and Paller's claim that a posterior
      old/new effect indexes familiarity for faces, along with a novel finding that
      recollection is associated with an anterior old/new effect. Importantly, and in
      contrast to Yovel and Paller, the old/new effects associated with familiarity and
      recollection were topographically dissociable, consistent with a dual-process
      view of recognition memory. The neural correlates of familiarity and recollection
      identified here for faces appear to be different from those typically observed,
      suggesting that the ERP old/new effects associated with episodic recognition are
      not the same under all circumstances.

PMID- 17451973
TI  - Central control of grasp: manipulation of objects with complex and simple
      dynamics.
AB  - We performed whole-brain fMRI to explore the neural mechanisms that contribute to
      the ability to manipulate an object with complex dynamics. Subjects grasped a
      weighted flexible ruler and balanced it in an unstable equilibrium position as an
      archetype of grasping an object with complex dynamics. This was contrasted with
      squeezing a soft foam ball as an archetype of grasping an object with simple
      dynamics. We hypothesized that changes in activity in primary motor cortex (MI)
      would be similar under the two conditions, since muscle activation was matched,
      which was confirmed. We hypothesized further that the cerebellum would be
      selectively activated when manipulating the flexible ruler because the ability to
      make the adjustments necessary to balance the ruler would require an internal
      dynamics model, represented in the cerebellum. As predicted, the ipsilateral
      cerebellum was strongly activated when balancing the weighted ruler whereas only
      moderate activation was found when squeezing the foam ball. We also found
      evidence for selective activation of areas, previously implicated in tactile
      object recognition, when holding the flexible ruler. We speculate that these
      areas, which include secondary somatosensory cortex (SII), Brodmann area 40 and
      insula, integrate tactile and proprioceptive information in the context of
      controlling the orientation of the flexible ruler and provide appropriate
      feedback to MI. We speculate that the failure to find activation of these areas
      when squeezing the ball was due to the fact that tactile stimulation was entirely
      self-produced, resulting in the attenuation of cortical sensory activity
      (Blakemore, S.-J., Wolpert, D.M., Frith, C.D., 1998. Central cancellation of self
      produced tickle sensation. Nat. Neurosci. 1, 635-640, Blakemore, S.-J., Frith,
      C.D., Wolpert, D.M., 2001. The cerebellum is involved in predicting the sensory
      consequences of action. NeuroReport 12, 1879-1884).

PMID- 17451974
TI  - Adaptation in human visual cortex as a mechanism for rapid discrimination of
      aversive stimuli.
AB  - The ability to react rapidly and efficiently to adverse stimuli is crucial for
      survival. Neuroscience and behavioral studies have converged to show that visual
      information associated with aversive content is processed quickly and accurately
      and is associated with rapid amplification of the neural responses. In
      particular, unpleasant visual information has repeatedly been shown to evoke
      increased cortical activity during early visual processing between 60 and 120 ms
      following the onset of a stimulus. However, the nature of these early responses
      is not well understood. Using neutral versus unpleasant colored pictures, the
      current report examines the time course of short-term changes in the human visual
      cortex when a subject is repeatedly exposed to simple grating stimuli in a
      classical conditioning paradigm. We analyzed changes in amplitude and synchrony
      of large-scale oscillatory activity across 2 days of testing, which included
      baseline measurements, 2 conditioning sessions, and a final extinction session.
      We found a gradual increase in amplitude and synchrony of very early cortical
      oscillations in the 20-35 Hz range across conditioning sessions, specifically for
      conditioned stimuli predicting aversive visual events. This increase for
      conditioned stimuli affected stimulus-locked cortical oscillations at a latency
      of around 60-90 ms and disappeared during extinction. Our findings suggest that
      reorganization of neural connectivity on the level of the visual cortex acts to
      optimize early perception of specific features indicative of emotional relevance.

PMID- 17451975
TI  - Hand bone midshaft enthesophytes: the influence of age, sex, and heritability.
AB  - OBJECTIVE: The aims of the present study were (1) to evaluate whether development
      of enthesophytes is an age- and/or sex-associated phenomenon; (2) to clarify
      whether enthesophyte development is controlled by genetics; (3) to evaluate the
      correlations between the enthesophytes and osteophytes of the hand joints.
      DESIGN: The studied cohort comprised 359 Chuvashian (Russian Federation)
      pedigrees (424 nuclear families) and included 786 males and 723 females aged 18
      90 years. The enthesophyte score (ES) was constructed as the overall number of
      enthesophytes at the midshaft of the phalanges of the second to the fifth fingers
      of both hands. The osteophyte score (OS) was constructed similarly. We used
      variance component (VC) analysis to examine the age-related patterns and compare
      the contribution of the genetic and common environmental factors to ES and OS
      variations. RESULTS AND CONCLUSIONS: After age 25, ES increases with age (on
      average linearly). Age explains 45% of the ES variation in males but only 25% of
      the variation in females, in contrast to about 75% of the variation of OS in both
      sexes. At any age, males showed higher ES than females and the difference between
      sexes increased with age. Genetic components explained 20% of enthesophyte
      development variation. We did not find common additive genetic factors for ES and
      OS. The correlation coefficients between ES and OS were r=0.62 (P=0.0001) in
      males and r=0.50 (P=0.0001) in females. After age adjustment, the correlation
      decreased to r=0.087 (P=0.014) and r=0.14 (P=0.001) correspondingly. Most
      probably, enthesophytes and osteophytes are manifestations of different
      etiological processes.

PMID- 17451976
TI  - Global molecular surveillance reveals novel Fusarium head blight species and
      trichothecene toxin diversity.
AB  - To expand our knowledge of Fusarium head blight (FHB) pathogen and trichothecene
      toxin diversity, a global collection of 2100 isolates was screened for novel
      genetic variation, resulting in the identification of 16 phylogenetically
      divergent FHB isolates. The affinities and taxonomic status of these novel
      isolates were evaluated via phylogenetic analyses of multilocus DNA sequence data
      (13 genes; 16.3 kb/strain) together with analyses of their morphology,
      pathogenicity to wheat, and trichothecene toxin potential. Based on the results
      of these analyses, we formally describe two novel species (Fusarium vorosii and
      Fusarium gerlachii) within the Fusarium graminearum species complex (Fg complex),
      and provide the first published report of Fg complex isolates with either a
      nivalenol or 3-acetyldeoxynivalenol chemotype within the U.S. In addition, we
      describe a highly divergent population of F. graminearum from the Gulf Coast of
      the U.S., and divergent isolates of F. acaciae-mearnsii from Australia and South
      Africa.

PMID- 17451977
TI  - Isolation of Serratia fonticola from skin lesions in a Nile Crocodile (Crocodylus
      niloticus) with an associated septicaemia.
AB  - This paper describes the first isolation of Serratia fonticola in a Nile
      Crocodile (Crocodylus niloticus). This organism was initially isolated from skin
      lesions and blood and subsequently from a variety of organs during necropsy. S.
      fonticola was confirmed as the pathogen causing the infection.

PMID- 17451978
TI  - Subclinical mastitis changes the patterns of maternal-offspring behaviour in
      dairy sheep.
AB  - Subclinical mastitis was induced by inoculating one mammary gland in dairy ewes
      (n=8) with a Staphylococcus simulans isolate; control ewes (n=4) were included.
      The milk yield of inoculated glands decreased (P<0.001), the California Mastitis
      Test (CMT) score increased and the organism could be recovered from the
      inoculated glands. With time, there was significantly increased frequency of
      "hindering sucking" (P=0.016) and "head up posture" (P<0.001) in the control
      ewes. Infected ewes had a significantly increased frequency of "vocalisation"
      (P=0.013) compared to controls. There was a significant difference in the
      frequency of "sucking attempt" and "successful suck" (P<0.05) behaviours between
      lambs of the two groups. Lambs of the challenged ewes also showed significantly
      increased frequency and duration of these behaviours towards the uninoculated
      glands of their dams, rather than to the challenged glands (P<0.05); no such
      difference was evident for the lambs of control ewes. It was concluded that
      subclinical mastitis alters the sucking behaviour of both ewes and lambs.

PMID- 17451979
TI  - Decreased perceptual learning ability in complex regional pain syndrome.
AB  - Recently, several functional imaging studies have shown that sensorimotor
      cortical representations may be changed in complex regional pain syndromes
      (CRPS). Therefore, we investigated tactile performance and tactile learning as
      indirect markers of cortical changes in patients with CRPS type I and controls.
      Patients had significant higher spatial discrimination thresholds at CRPS
      affected extremities compared to both unaffected sides and control subjects.
      Furthermore, in order to improve tactile spatial acuity we used a Hebbian
      stimulation protocol of tactile coactivation. This consistently improved tactile
      acuity, both in controls and patients. However, the gain of performance was
      significantly lower on the CRPS-affected side implying an impaired perceptual
      learning ability. Therefore, we provide further support for an involvement of the
      CNS in CRPS, which may have implications to future neurorehabilitation strategies
      for this disease.

PMID- 17451980
TI  - Placebo response in the prophylaxis of migraine: a meta-analysis.
AB  - BACKGROUND: Migraine constitutes a good model for the study of placebo response.
      It is a well-defined disease, affects a large population and a great number of
      clinical trials have been performed, which have given homogeneous outcomes. AIM:
      The aim of this meta-analysis is to evaluate the placebo response rate in
      migraine prophylaxis in all published clinical trials since 1988 and to estimate
      the influence of study design in response variability. METHODS: A computer-based
      information search was conducted on the Medline database. The outcomes studied
      were patients who improved (reduction in migraine attacks of 50% or more);
      attacks per month, and patients with adverse events. Study design and countries
      in which the study was carried out were also analysed. The meta-analysis was
      computed using the Mantel-Haenszel test. RESULTS: In the final analysis, 32
      papers were considered. The pooled estimate of the placebo response (patients who
      improved) was 21%. The placebo response rates were significantly higher in
      studies with a parallel design than those in cross-over studies (p<0.01). This
      response was also higher in European studies than in those performed in North
      America (p<0.001). Adverse events occurred in 30% of the patients who took a
      placebo, and the percentage of patients with adverse events was significantly
      higher in the North American studies than in those conducted in Europe (p<0.01).
      CONCLUSION: These data reinforce the need to consider the placebo effect when
      ascertaining the true therapeutic effect of any drug, as well as to design any
      clinical trial in the prophylaxis of migraine.

PMID- 17451981
TI  - Targeted-ROI imaging in electron paramagnetic resonance imaging.
AB  - Electron paramagnetic resonance imaging (EPRI) is a technique that has been used
      for in vivo oxygen imaging of small animals. In continuous wave (CW) EPRI, the
      measurement can be interpreted as a sampled 4D Radon transform of the image
      function. The conventional filtered-backprojection (FBP) algorithm has been used
      widely for reconstructing images from full knowledge of the Radon transform
      acquired in CW EPRI. In practical applications of CW EPRI, one often is
      interested in information only in a region of interest (ROI) within the imaged
      subject. It is desirable to accurately reconstruct an ROI image only from partial
      knowledge of the Radon transform because acquisition of the partial data set can
      lead to considerable reduction of imaging time. The conventional FBP algorithm
      cannot, however, reconstruct accurate ROI images from partial knowledge of the
      Radon transform of even dimension. In this work, we describe two new algorithms,
      which are referred to as the backprojection filtration (BPF) and minimum-data
      filtered-backprojection (MDFBP) algorithms, for accurate ROI-image reconstruction
      from a partial Radon transform (or, truncated Radon transform) in CW EPRI. We
      have also performed numerical studies in the context of ROI-image reconstruction
      of a synthetic 2D image with density similar to that found in a small animal
      EPRI. This demonstrates both the inadequacy of the conventional FBP algorithm and
      the success of BPF and MDFBP algorithms in ROI reconstruction. The proposed ROI
      imaging approach promises a means to substantially reduce image acquisition time
      in CW EPRI.

PMID- 17451982
TI  - Stepwise dissection and visualization of the catalytic mechanism of haloalkane
      dehalogenase LinB using molecular dynamics simulations and computer graphics.
AB  - The different steps of the dehalogenation reaction carried out by LinB on three
      different substrates have been characterized using a combination of quantum
      mechanical calculations and molecular dynamics simulations. This has allowed us
      to obtain information in atomic detail about each step of the reaction mechanism,
      that is, substrate entrance and achievement of the near-attack conformation,
      transition state stabilization within the active site, halide stabilization,
      water molecule activation and subsequent hydrolytic attack on the ester
      intermediate with formation of alcohol, and finally product release. Importantly,
      no bias or external forces were applied during the whole procedure so that both
      intermediates and products were completely free to sample configuration space in
      order to adapt to the plasticity of the active site and/or search for an exit.
      Differences in substrate reactivity were found to be correlated with the ease of
      adopting the near-attack conformation and two different exit pathways were found
      for product release that do not interfere with substrate entrance. Additional
      support for the different entry and exit pathways was independently obtained from
      an examination of the enzyme's normal modes.

PMID- 17451983
TI  - Modeling of alphak/gamma2 (k=1, 2, 3 and 5) interface of GABA A receptor and
      docking studies with zolpidem: implications for selectivity.
AB  - The three-dimensional models of the alphak/gamma2 (k=1, 2, 3 and 5) interface of
      GABA(A) receptors, which included the agonist-binding site, were constructed and
      validated by molecular modeling technology. To investigate the mechanism of alpha
      subunit selectivity of zolpidem, docking calculations were used to illustrate the
      potential binding modes of zolpidem with different alpha subtypes. The results
      revealed that there were three reasons resulting in the distinct binding affinity
      of zolpidem to different alpha subtype. Firstly, the number of hydrogen bonds of
      agonist-receptor complex would determine the magnitude of binding affinity.
      Secondly, the His residue in loop A of alpha subunit was indicated as a key role
      of benzodiazepine binding. Thirdly, the side chain of Glu in loop C reduced the
      affinity of zolpidem to those receptors containing alpha2, alpha3 or alpha5
      subunits.

PMID- 17451984
TI  - Effect of precision error on T-scores and the diagnostic classification of bone
      status.
AB  - We quantified confidence intervals (CIs) for T-scores for the lumbar spine and
      hip and determined the practical effect (impact on diagnosis) of variability
      around the T-score cutpoint of -2.5. Using precision data from the literature for
      GE Lunar Prodigy dual-energy X-ray absorptiometry (DXA) systems, the 95% CI for
      the T-score was +/-0.23 at the lumbar spine (L1-L4), +/- 0.20 at the total hip,
      and +/-0.41 at the femoral neck. Thus, T-score variations of +/-0.23 or less at
      the spine, +/-0.20 at the total hip, and +/-0.41 at the femoral neck are not
      statistically significant. When diagnosing osteoporosis, T-scores in the interval
      -2.3 to -2.7 for spine or total hip (after rounding to conform to guidelines from
      the International Society for Clinical Densitometry) and -2.1 to -2.9 for femoral
      neck are not statistically different from -2.5. Better precision values resulted
      in smaller 95% CIs. This concept was applied to actual clinical data using
      Hologic DXA systems. The study cohort comprised 2388 white women with either
      normal or osteopenic spines in whom the densitometric diagnosis of osteoporosis
      would be determined by hip T-scores. When evaluating actual patient T-scores in
      the range -2.5+/-95% CI, we found that the diagnosis was indeterminate in
      approximately 12% of women when T-scores for femoral neck were used and in 4% of
      women when T-scores for total hip were used, with uncertainty as to whether the
      classification was osteopenia or osteoporosis. We conclude that precision
      influences the variability around T-scores and that this variability affects the
      reliability of diagnostic classification.

PMID- 17451985
TI  - Is discordance in bone measurements affected by body composition or
      anthropometry? A comparative study between peripheral and central devices.
AB  - Screening of osteoporosis using peripheral bone measurements has become more
      common, even though diagnostic discrepancies are known to exist between
      peripheral dual-energy X-ray (pDXA) or quantitative ultrasound (QUS) and central
      DXA measurements. Values of diagnostic parameters such as bone mineral density,
      speed of (ultra)sound, and broadband ultrasound attenuation are affected by bone
      size and soft tissue composition. However, their significance for the discordance
      between peripheral and central techniques is unclear. In this study, bone status
      and total body composition of 139 women (mean age 68.3 yr [1.7 SD], mean body
      mass index 26.5 kg/m2 [3.6 SD]) were assessed by 3 GE Lunar devices. Heel pDXA
      and heel QUS were conducted using peripheral instantaneous X-ray imaging (PIXI)
      and Achilles, respectively, and central DXA measurements were taken at the
      posterior-anterior lumbar spine (L2-L4) and at the left femoral neck using
      Prodigy. Positive significant associations were found between body height or fat
      (%) and most DXA or QUS parameters. The discordance between the site-dependent
      DXA or QUS T-score values typically increased (p<0.05) as a function of body
      weight or fat (%), but not with body height. On an average, body adiposity
      accounted for less than 11% of the differences between the techniques; however,
      increase of total body fat from 20% to 45% led to a discrepancy of one T-score
      between DXA(HEEL) and QUS(HEEL). To avoid diagnostic bias, comparative assessment
      of the devices using the same population is recommended.

PMID- 17451986
TI  - Does a 5500-km swim trial stimulate early sexual maturation in the European eel
      (Anguilla anguilla L.)?
AB  - The catadromous European eel (Anguilla anguilla L.) undertakes a 6000-km spawning
      migration from its freshwater habitats to the Sargasso Sea. In large Blazka swim
      tunnels of 127 l, the physiological effect of such a prolonged swimming
      performance on sexual maturation in adult female eels was investigated. Two
      groups of eels were placed in swim tunnels for 173 days, one group was able to
      swim at 0.5 body lengths/second (Swim group) covering a distance of c. 5500-km
      over the experimental period, and one group kept in static (End Control group). A
      control group was sampled at the start of the experiment in order to determine
      the initial stage of reproductive development (Initial Control group). At the end
      of the swim trial, the maturation parameters 11-ketotestosterone, pituitary
      levels of LH and plasma levels of estradiol were higher (although not
      significantly) in the Swim compared to the End Control group. In addition, no
      significant differences were observed in most measured morphometric and
      reproductive parameters, including eye-index, gonadosomatic index, hepatosomatic
      index, and plasma levels of vitellogenin, cortisol and melanophore-stimulating
      hormone (MSH). Also, pituitary levels of both MSH, and adrenocorticotropic
      hormone (ACTH) were unaffected. In contrast, the oocyte diameter was found to be
      significantly higher in the Swim compared to the End Control group. Based on
      these observations we conclude that a period of prolonged swimming might be a
      physiological stimulus necessary for the onset of maturation in the European eel.

PMID- 17451987
TI  - The functional ontogeny of the teleost gill: which comes first, gas or ion
      exchange?
AB  - For most of the last century, the need to obtain sufficient oxygen to meet the
      respiratory requirements of the tissues was viewed as the primary selective
      pressure driving gill development in teleost fish. Recently, however, it has been
      suggested that ionoregulatory pressures may actually be more important. This
      manuscript reviews the theoretical and empirical evidence dealing with the
      functional ontogeny of the gill in the context of the oxygen and ionoregulatory
      hypotheses. Gas and ion exchange are subject to similar geometric constraints in
      developing fish. Both initially are exclusively cutaneous but shift to the gill
      with tissue growth because of declining surface-to-volume ratios. Based on the
      appearance of mitochondria-rich cells (MRCs), ionoregulatory activity shifts to
      the gill in advance of gas exchange. In every species examined to date, MRCs
      appear on the developing gill in advance of secondary lamellae, the definitive
      gas exchange structure of the adult gill. Biochemical and histochemical studies
      indicate that these early branchial MRCs are actively involved in ion exchange.
      In some cases, the specific activity is many times greater than in the adult
      gill. In contrast, O2 microelectrode and hemoglobin ablation experiments suggest
      that the early gill contributes little O2 to the general systemic circulation.
      Any oxygen taken up appears to be consumed locally. Functional ablation
      experiments with zebrafish indicated that the larval gill became essential for
      ion balance well before it was needed for O2 uptake. Similar experiments with
      rainbow trout, however, found that the gill became essential in terms of gas and
      ion exchange at about the same time. On balance, the evidence appears to favour
      the ionoregulatory hypothesis but the oxygen hypothesis cannot be absolutely
      rejected without more information. Some of the major deficiencies in our
      knowledge regarding the transition from cutaneous to branchial gas and ion
      exchange are highlighted and potential implications of the ionoregulatory
      hypothesis are discussed.

PMID- 17451988
TI  - Parvalbumin expression in trout swimming muscle correlates with relaxation rate.
AB  - Rainbow trout (Oncorhynchus mykiss) display longitudinal and developmental shifts
      in muscle relaxation rate. This study aimed to determine the role of variations
      in parvalbumin content in modulating muscle relaxation. Parvalbumin is a low
      molecular weight protein that buffers myoplasmic Ca2+ and enhances muscle
      relaxation. In some fish, longitudinal variations in muscle relaxation have been
      linked to variations in the total amount of parvalbumin present in muscle and in
      the relative expression of two parvalbumin isoforms. We have demonstrated
      previously that anterior slow-twitch or red myotomal muscle relaxes more rapidly
      than that from the posterior for both rainbow and brook trout. Further, younger
      rainbow trout parr have faster red muscle relaxation rates than older smolts.
      Here we report similar results for fast-twitch or white muscle. We quantified the
      parvalbumin expression in red and white muscle from different body positions of
      rainbow trout parr and smolts and for brook trout (Salvelinus fontinalis) adults.
      There was a significant shift in total parvalbumin content of muscle: the faster
      muscle from the anterior myotome contained greater amounts of parvalbumin. For
      brook trout, longitudinal variation in relaxation rate was also associated with
      shifts in the relative expression of the two parvalbumin isoforms. The faster
      muscle of parr contained more parvalbumin. Lastly, trout white muscle tended to
      have higher levels of parvalbumin and greater levels of the Parv2 (relative to
      Parv1) isoform as compared to red muscle. Parvalbumin expression correlated with
      muscle relaxation rate in trout, although there were species-specific differences
      in the importance of altering total parvalbumin content versus shifts in relative
      parvalbumin isoform expression.

PMID- 17451989
TI  - Air-breathing catfish, Clarias batrachus upregulates glutamine synthetase and
      carbamyl phosphate synthetase III during exposure to high external ammonia.
AB  - We assessed the possible upregulation of glutamine synthetase (GS) and typical
      'fish type' carbamyl phosphate synthetase III (CPS III) in detoxification of
      ammonia in different tissues of the walking catfish (Clarias batrachus) during
      exposure to 25 mM NH(4)Cl for 7 days. Exogenous ammonia led to an increase in
      ammonia and urea concentrations in different tissues. The results revealed the
      presence of relatively high levels of GS activity in the brain, liver and kidney,
      unexpectedly, also in the muscle, and even higher levels in the intestine and
      stomach. Exposure to high external ammonia (HEA) caused significant increase of
      activities of GS, CPS III and CPS I-like enzymes, accompanied with the
      upregulation of GS and CPS III enzyme proteins in different tissues. Exposure to
      HEA also led to a sharp rise of plasma cortisol level, suggesting being one of
      the primary causes of upregulation of GS and CPS III enzymes activity. Liver
      perfusion experiments further revealed that exposure to HEA enhances the capacity
      of trapping ammonia to glutamine and urea by the liver of walking catfish. These
      results suggest that the upregulation of GS and CPS III activity in walking
      catfish during exposure to HEA plays critical roles to ameliorate the toxic
      ammonia to glutamine, and also to urea via the induced ornithine-urea cycle
      possibly through the involvement of cortisol.

PMID- 17451990
TI  - Functional expression of prokaryotic and eukaryotic genes in Escherichia coli for
      conversion of glucose to p-hydroxystyrene.
AB  - The chemical monomer p-hydroxystyrene (pHS) is used for producing a number of
      important industrial polymers from petroleum-based feedstocks. In an alternative
      approach, the microbial production of pHS can be envisioned by linking together a
      number of different metabolic pathways, of which those based on using glucose for
      carbon and energy are currently the most economical. The biological process
      conserves petroleum when glucose is converted to the aromatic amino acid L
      tyrosine, which is deaminated by a tyrosine/phenylalanine ammonia-lyase (PAL/TAL)
      enzyme to yield p-hydroxycinnamic acid (pHCA). Subsequent decarboxylation of pHCA
      gives rise to pHS. Bacteria able to efficiently decarboxylate pHCA to pHS using a
      pHCA decarboxylase (PDC) include Bacillus subtilis, Pseudomonas fluorescens and
      Lactobacillus plantarum. Both B. subtilis and L. plantarum possess high levels of
      pHCA-inducible decarboxylase activity and were chosen for further studies. The
      genes encoding PDC in these organisms were cloned and the pHCA decarboxylase
      expressed in Escherichia coli strains co-transformed with a plasmid encoding a
      bifunctional PAL/TAL enzyme from the yeast Rhodotorula glutinis. Production of
      pHS from glucose was ten-fold greater for the expressed L. plantarum pdc gene
      (0.11mM), compared to that obtained when the B. subtilis PDC gene (padC) was
      used. An E. coli strain (WWQ51.1) expressing both tyrosine ammonia-lyase(PAL) and
      pHCA decarboxylase (pdc), when grown in a 14L fermentor and under phosphate
      limited conditions, produced 0.4g/L of pHS from glucose. We, therefore,
      demonstrate pHS production from an inexpensive carbohydrate feedstock by
      fermentation using a novel metabolic pathway comprising genes from E. coli, L.
      plantarum and R. glutinis.

PMID- 17451991
TI  - A prospective investigation of the prevalence and prognostic significance of
      weight loss and changes in body condition in feline cancer patients.
AB  - The objectives of this study were to prospectively identify and characterize
      weight loss and changes in body condition in feline cancer patients and to
      investigate the prognostic significance of these findings. Fifty-seven cats with
      neoplasia were evaluated. Body condition was assessed with a nine-point scoring
      system (BCS) and multiple sites were assessed for muscle and fat mass using four
      point scoring systems. Feline cancer patients had a mean BCS of 4.4+/-2.1 kg
      (1=cachectic, 5=optimal, 9=obese). Fat mass was reduced in both sites assessed in
      60% of the patients. Muscle mass was reduced at all three sites assessed in 91%
      of the patients. Feline cancer patients having a BCS <5 had a median survival
      time (MST) of 3.3 months compared to that of 16.7 months for cats with a BCS of >
      or = 5 (P=0.008).

PMID- 17451992
TI  - [Ambulatory breast surgery. Value of sentinel node biopsy under local anesthesia
      in breast cancer].

PMID- 17451993
TI  - Intracellular labile iron.
AB  - Cells maintain organellar pools of "labile iron" (LI), despite its propensity for
      catalyzing the formation of reactive oxygen species. These pools are identifiable
      by iron-chelating probes and accessible to pharmacological agents. Cytosolic LI
      has been assumed to have a dual function: providing a rapidly adjustable source
      of iron for immediate metabolic utilization, and for sensing by iron-regulatory
      proteins (IRPs) that regulate iron uptake and compartmentalization via
      transferrin receptors and ferritin. However, it now appears that IRPs may respond
      both to fluctuations in LI per se and to secondary signals associated with redox
      active species. Recent information also indicates that iron can be delivered to
      mitochondria via pathways that circumvent cytosolic LI, suggesting possible
      alternative mechanisms of cell iron mobilization and trafficking. We discuss the
      changing views of intracellular LI pools in relation to iron homeostasis and
      cellular distribution in physiological and pathological states.

PMID- 17451994
TI  - Vicia root-mirconucleus and sister chromatid exchange assays on the genotoxicity
      of selenium compounds.
AB  - Selenium (Se) is an important metalloid with industrial, environmental,
      biological and toxicological significance. Excessive selenium in soil and water
      may contribute to environmental selenium pollution, and affect plant growth and
      human health. By using Vicia faba micronucleus (MN) and sister chromatid exchange
      (SCE) tests, possible genotoxicity of sodium selenite and sodium biselenite was
      evaluated in this study. The results showed that sodium selenite, at
      concentrations from 0.01 to 10.0mg/L, induced a 1.9-3.9-fold increase in MN
      frequency and a 1.5-1.6-fold increase in SCE frequency, with a statistically
      significantly difference from the control (P<0.05 and 0.01, respectively). Sodium
      selenite also caused mitotic delay and a 15-80% decrease in mitotic indices (MI),
      but at the lowest concentration (0.005mg/L), it slightly stimulated mitotic
      activity. Similarly, the frequencies of MN and SCE also increased significantly
      in sodium biselenite treated samples, with MI decline only at relatively higher
      effective concentrations. Results of the present study suggest that selenite is
      genotoxic to V. faba root cells and may be a genotoxic risk to human health.

PMID- 17451995
TI  - A review of the mutagenicity and rodent carcinogenicity of ambient air.
AB  - Although ambient air was first shown to be carcinogenic in 1947 and mutagenic in
      1975, no overarching review of the subsequent literature has been produced.
      Recently, Claxton et al. [L.D. Claxton, P.P. Matthews, S.H. Warren, The
      genotoxicity of ambient outdoor air, a review: Salmonella mutagenicity, Mutat.
      Res./Rev. Mutat. Res. 567 (2004) 347-399] reviewed the literature on the
      mutagenicity of urban air in the Salmonella mutagenicity assay. Here, we review
      the literature on the mutagenicity of urban air in other test systems and review
      the carcinogenicity of urban air in experimental systems. Urban air was
      carcinogenic in most of the reports involving rodents. Studies ascribed
      carcinogenic activity primarily to PAHs, nitroarenes, and other aromatic
      compounds. Atmospheric conditions, along with the levels and types of pollutants,
      contributed to the variations in carcinogenic and mutagenic activity of air from
      different metropolitan areas. The majority of the mutagenesis literature was in
      the Salmonella assay (50%), with plant systems accounting for most of the rest
      (31%). The present data give little support to the use of plant systems to
      compare air mutagenicity among multiple sites or studies. Studies in mice have
      shown that particulate air pollution causes germ-cell mutations. Air sheds
      contain similar types and classes of mutagens; however, the levels of these
      compounds vary considerably among air sheds. Combustion emissions were associated
      with much of the mutagenicity and carcinogenicity of urban air. Most studies
      focused on the particulate fraction; thus, additional work is needed on the
      volatile and semi-volatile fractions, metals, and atmospheric transformation.
      Smaller particles have greater percentages of extractable organic material and
      are more mutagenic than larger particles. Although hundreds of genotoxic
      compounds have been identified in ambient air, only a few (<25) are routinely
      monitored, emphasizing the value of coupling bioassay with chemistry in the
      monitoring of air for carcinogenic and mutagenic activities and compounds.

PMID- 17451996
TI  - An iron(III) selective dendrite chelator based on polyamidoamine dendrimer
      modified with 4-bromo-1,8-naphthalimide.
AB  - A new 4-bromo-1,8-naphthalimide-labelled polyamidoamine (PAMAM) dendrimer from
      zero generation has been synthesised and characterised. Its functional
      characteristics, determined in acetonitrile solvent are discussed. The ability of
      the dendrimer to detect metal cations has been evaluated in acetonitrile by
      monitoring the quenching of the fluorescence intensity. Different metal cations
      have been tested Co(2+), Ni(2+), Cu(2+) and Fe(3+) for the purpose. The results
      have shown clearly that only Fe(3+) could be efficiently detected using the
      dendrimer.

PMID- 17451997
TI  - Solvent polarity induced structural changes in 2,6-diamino-9,10-anthraquinone
      dye.
AB  - Photophysical properties of 2,6-diamino-9,10-anthraquinone (2,6-DAAQ) dye have
      been investigated in different solvents and solvent mixtures. The fluorescence
      quantum yields, fluorescence lifetimes, radiative rate constants, nonradiative
      rate constants and absorption and fluorescence spectral characteristics show
      unusual deviations in the lower polarity aprotic solvents in comparison to those
      in other aprotic solvents of medium to higher polarities. The results indicate
      that the dye exists in different structural forms in the lower and in the medium
      to higher polarity solvents. Drawing an analogy with the results reported for
      other amino-substituted dyes, it is inferred that 2,6-DAAQ dye adopts a planar
      intramolecular charge transfer (ICT) structure in medium to higher polarity
      solvents, where the amino lone pairs are in good resonance with the anthraquinone
      pi-cloud. In the lower polarity solvents, however, the dye is inferred to exist
      in a nonplanar structure where the amino lone pairs are not in good resonance
      with the anthraquinone pi-cloud. Due to these structural differences, the dye
      displays significantly different photophysical behavior in the lower polarity
      solvents than in the other solvents of medium to higher polarities. Supportive
      evidence for the above structural changes has been obtained from ab initio
      quantum chemical calculations on the structures of the dye under different
      conditions. Unusual deviations in the photophysical properties of 2,6-DAAQ dye in
      protic solvents in comparison to those in aprotic solvents of similar polarities
      are attributed to the intermolecular hydrogen bonding effect involving the OH
      groups of the protic solvents and the quinonoid oxygens of the dye.

PMID- 17451998
TI  - Solvatochromic study of 1,2-dihydroxyanthraquinone in neat and binary solvent
      mixtures.
AB  - Preferential solvation of a solvatochromic probe has been studied in binary
      mixtures comprising of a non-protic and a protic solvent. The non-protic solvents
      employed are carbon tetrachloride (CCl(4)), acetonitrile (AcN) and N,N-dimethyl
      formamide (DMF) and the protic solvents are methanol (MeOH) and ethanol (EtOH).
      The probe molecule exhibits different spectroscopic characteristics depending
      upon the properties of the solubilizing media. The observed spectral features
      provide an indication of the microenvironment immediately surrounding the probe.
      Solvatochromic shifts of the ground and excited states of the probe were analysed
      by monitoring the charge transfer absorption band and the fluorescence emission
      spectra in terms of the solute-solvent and solvent-solvent interactions.
      Fluorescence emission spectra show the dual emission due to excited state proton
      transfer nature of the probe molecule. The effect of solvent and the excitation
      energy on dual emission are also studied. The observed magnitude of the Stokes
      shift in the above solvents has been used to deduce experimentally the dipole
      moment ratio of the probe molecule for the excited state to the ground state. The
      dipole moment of excited state is higher than the ground state.

PMID- 17451999
TI  - Hepatitis B virus (HBV) genotypes/subgenotypes in China: mutations in core
      promoter and precore/core and their clinical implications.
AB  - BACKGROUND: The association of hepatitis B virus (HBV) genotypes with clinical
      course of infection is increasingly recognized. OBJECTIVES: In order to
      investigate the genetic diversity of HBV and its clinical implications, 241 HBV
      infected patients including 34 with hepatocellular carcinoma (HCC) were enrolled
      in this study. METHODS: HBV genotyping was performed with an ELISA assay. HBV
      subgenotypes were determined by PCR-RFLP. HBV core promoter/precore/core
      mutations were analyzed by direct sequencing. RESULTS: The overall prevalence of
      HBV/B and C was 65% and 33%, respectively. Among HBV/C, 42% were Cs/C1 and 58%
      were Ce/C2. The HBV/C1 was only found in the patients originating from Southern
      China (p=0.0001). Among HCC patients, HBV/C2 was only found in the elder age
      group (> or =51 years; p<0.05) and HBV/Ba was associated with young HCC patients
      (<35 years). Mutations associated with HCC were V1753 and T1762/A1764 (p<0.01).
      The prevalence of the V1753 was higher in HBV/C1 strains (p<0.04), A1898 was only
      found among HBV/C1 (p=0.056). T1762/A1764 was frequently demonstrated in both
      subgenotypes. The T1858 (90%) and A1896 (40%) mutations were most frequent in
      HBV/C2 (p<0.008). CONCLUSIONS: HBV/C1 and HBV/C2 have distinct geographic
      distributions in China. V1753 in addition to T1762/A1764 double mutation in the
      basal core promoter region seems to be associated with HCC development,
      especially in the patients with HBV/C1.

PMID- 17452000
TI  - Performance of six influenza rapid tests in detecting human influenza in clinical
      specimens.
AB  - BACKGROUND: The rapid diagnosis of influenza can alter the management of a
      patient's illness, resulting in reduced antibiotic usage, correct use of
      influenza antivirals and reduced length of stay in hospital emergency
      departments. The rapid tests have also been used to detect outbreaks in
      institutions and may play a role in pandemic influenza control. OBJECTIVES: To
      test six different rapid influenza tests, in a head-to-head comparison for the
      detection of seasonal influenza types A and B, compared to laboratory-based
      tests. STUDY DESIGN: One hundred and seventy-seven clinical specimens taken from
      mostly paediatric patients between June and October 2006 were tested using six
      influenza diagnostic tests and three laboratory-based techniques
      (immunofluorescence, cell culture and real-time RT-PCR). RESULTS AND CONCLUSION:
      Compared with cell culture, five of the rapid tests (Binax Now Influenza A&B,
      Directigen EZ Flu A+B, Denka Seiken Quick Ex-Flu, Fujirebio Espline Influenza A&B
      N, and Quidel QuickVue Influenza A+B Test) demonstrated a similar influenza A
      sensitivity of between 67-71% and a specificity of 99-100%, however one rapid
      test (Rockeby Influenza A Antigen Test) had a significantly lower influenza A
      sensitivity of only 10% (specificity was 100%). For the five kits that detected
      influenza B antigen, sensitivity was considerably lower than that seen for
      influenza A (sensitivity for all the kits was 30%), although the number of
      specimens containing influenza B viruses was low.

PMID- 17452001
TI  - Human respiratory syncytial virus (hRSV) RNA quantification in nasopharyngeal
      secretions identifies the hRSV etiologic role in acute respiratory tract
      infections of hospitalized infants.
AB  - BACKGROUND: Human respiratory syncytial virus (hRSV) detection in nasopharyngeal
      aspirates (NPAs) from infants with acute respiratory tract infection (ARTI) does
      not prove the hRSV etiology of the current ARTI episode. HRSV RNA quantification
      may help in affording this issue. OBJECTIVES: hRSV was detected by quantitative
      reverse transcription-PCR in NPAs taken upon admission to hospital and, whenever
      possible, at discharge and subsequent medical visits. STUDY DESIGN: Prospective
      study, including 63 infants affected by either hRSV upper or lower ARTI. RESULTS:
      Based on the kinetics of viral load, hRSV etiology was identified in 25 infants
      in whom hRSV load dropped from 2.5 x 10(6) upon admission (presence of
      respiratory symptoms) to 7.5 x 10(2)RNAcopies/ml NPA upon discharge (absence of
      symptoms) after a median time of 5 days, and in 19 infants, in whom hRSV load was
      determined at admission only, in association with clinical symptoms (2.4 x
      10(6)copies/ml). Furthermore, low levels of hRSV RNA (<1 x 10(5)copies/ml NPA)
      identified 14 patients with non-hRSV ARTI. Finally, in 14 infants with hRSV
      coinfections or sequential infections, hRSV quantification defined the hRSV role
      in the current ARTI episode. CONCLUSIONS: hRSV RNA quantification is critical in
      defining the hRSV role in respiratory infections.

PMID- 17452002
TI  - Liver enzyme flares and occult hepatitis B in persons with chronic hepatitis C
      infection.
AB  - BACKGROUND: Occult hepatitis B (HBV) has been reported in numerous clinical
      settings, but it remains unclear whether occult HBV contributes to liver damage.
      Given that typical chronic HBV infections often have periodic flairs in viral
      replication and liver damage, we hypothesized that occult HBV may also have
      flares in viral replication that are associated with increased liver enzymes.
      STUDY DESIGN: We screened hepatitis B surface antigen negative injection drug
      users with untreated chronic hepatitis C viral (HCV) infection for unexplained
      ALT/AST flares. To further enrich for individuals with possible occult HBV
      flares, we studied those individuals whose flares were associated with IgM
      antibodies to hepatitis B core antigen. Serum samples were assayed for HBV DNA
      and serologies were performed in serum collected 6 months before, at the time,
      and 6 months after the flare. HCV RNA levels were also determined. Controls
      consisted of individuals who also had ALT/AST flares but who were negative for
      IgM antibodies to hepatitis B core antigen. RESULTS: Seven study cases and eight
      control cases were identified. HBV DNA was detectable during the enzyme flares in
      7/7 study cases versus 3/8 controls, p=0.026. HBV DNA levels during the flare
      were low, averaging 1943 +/- 2341 copies/ml, but were higher in study cases
      versus controls, p=0.002. No change in HCV levels was associated with the flares.
      CONCLUSIONS: In this population at high risk for occult HBV, AST/ALT flares can
      be associated with detection of HBV DNA. These findings may link occult hepatitis
      B to liver injury.

PMID- 17452003
TI  - Effects of spinal cord stimulation on the cortical somatosensory evoked
      potentials in failed back surgery syndrome patients.
AB  - OBJECTIVE: To evaluate the functional activation of the somatosensory cortical
      regions in neuropathic pain patients during therapeutic spinal cord stimulation
      (SCS). METHODS: In nine failed back surgery syndrome patients, the left tibial
      and the left sural nerves were stimulated in two sessions with intensities at
      motor and pain thresholds, respectively. The cortical somatosensory evoked
      potentials were analyzed using source dipole analysis based on 111 EEG signals.
      RESULTS: The short-latency components of the source located in the right primary
      somatosensory cortex (SI: 43, 54 and 65ms) after tibial nerve stimulation, the
      mid-latency SI component (87ms) after sural nerve stimulation, and the mid
      latency components in the right (approximately 161ms) and left (approximately
      168ms) secondary somatosensory cortices (SII) were smaller in the presence of SCS
      than in absence of SCS. The long-latency source component arising from the mid
      cingulate cortex (approximately 313ms) was smaller for tibial and larger for
      sural nerve stimuli during SCS periods compared to periods without SCS.
      CONCLUSIONS: SCS attenuates the somatosensory processing in the SI and SII. In
      the mid-cingulate cortex, the effect of SCS depends on the type of stimulation
      and nerve fibers involved. SIGNIFICANCE: Results suggest that the effects of SCS
      on cortical somatosensory processing may contribute to a reduction of allodynia
      during SCS.

PMID- 17452004
TI  - Fibration, fibrillation, and fasciculation: say what you see.

PMID- 17452005
TI  - Altered soleus responses to magnetic stimulation in pure cerebellar ataxia.
AB  - OBJECTIVE: Transcranial magnetic stimulation (TMS) over the leg motor area
      elicits a soleus primary response (SPR) and a soleus late response (SLR). We
      evaluated the influence of the cerebellofugal pathway on the SPR and SLR in
      patients with 'pure' cerebellar ataxia. METHODS: SPRs and SLRs were recorded from
      11 healthy subjects and 9 patients with 'pure' cerebellar cortical degeneration;
      5 with spinocerebellar ataxia type 6 (SCA6), and 4 with late cortical cerebellar
      ataxia (LCCA). In addition, three patients with localized cerebellar lesions were
      tested. RESULTS: The SPR latency was significantly longer in patients than in
      controls, but primary responses in the tibialis anterior muscle were normal. The
      frequency of abnormal SLR was 38.9% in the supine position and 83.3% in the
      standing position. Two out of three patients with localized cerebellar lesions
      also showed abnormal SLR. CONCLUSIONS: Altered SPRs in patients may result from a
      dysfunction of the primary motor cortex caused by crossed cerebello-cerebral
      diaschisis. In addition, our results suggest that 'pure' cerebellar degeneration
      involves the mechanism responsible for evoking SLR which is related to the
      control of posture. SIGNIFICANCE: SLR can be a useful neurophysiological
      parameter for evaluating cerebellofugal function.

PMID- 17452006
TI  - Cortical sources of awake scalp EEG in eating disorders.
AB  - OBJECTIVE: To investigate quantitative EEG (qEEG) in anorexia nervosa (AN) and
      bulimia nervosa (BN) in comparison with healthy controls. METHODS: Resting EEG
      was recorded in 30 healthy females (age: 27.1+/-5.5), 16-AN females (age: 26.4+/
      9.5) and 12-BN females (age: 27.0+/-6.3). Cortical EEG sources (delta, theta,
      alpha 1, alpha 2, beta 1, beta 2) were modeled by LORETA solutions. The
      statistical analysis was performed considering the factors Group, power Band, and
      region of interest (central, frontal, parietal, occipital, temporal, limbic).
      RESULTS: Alpha 1 sources in central, parietal, occipital and limbic areas showed
      a greater amplitude in Controls versus AN and BN groups. Alpha 2 sources in
      parietal, occipital and limbic areas showed a greater amplitude in Controls than
      in both AN and BN groups. Alpha 1 sources in temporal area showed a greater
      amplitude in Controls compared to both the BN and AN groups as well as in the BN
      group compared to AN group. Central alpha 1 source correlated significantly with
      BMI in patients. CONCLUSIONS: These results support the hypothesis that eating
      disorders are related to altered mechanisms of cortical neural synchronization,
      especially in rolandic alpha rhythms. SIGNIFICANCE: To our knowledge this is the
      first study by LORETA able to detect modifications of cortical EEG activity in
      eating disorders.

PMID- 17452007
TI  - Use of magnetoencephalography in the presurgical evaluation of epilepsy patients.
AB  - Magnetoencephalography (MEG) is used twofold for presurgical evaluation of
      patients with medically intractable partial epilepsy; to identify epileptogenic
      focus and to investigate functions of cortical areas at or near the epileptogenic
      focus or structural lesion. For the precise localization of the current source of
      epileptic discharge, the question as to whether MEG is superior to
      electroencephalography (EEG) is often addressed. To answer this question, so many
      factors, both biologically and technically related, have to be taken into
      consideration. The biological factors include the magnitude of epileptic
      discharge, its distribution over the cortex, depth of its source from the head
      surface, and the proportion of large pyramidal neurons tangentially oriented with
      respect to the head surface within the cortical area. The technical factors
      include the quality of the recording instrument such as the number of sensors and
      the use of gradiometer vs. magnetometer, the employed method of source analysis,
      and availability of experts in each institute. As far as the importance of ictal
      recording is emphasized, long-term video/EEG monitoring is of utmost importance.
      Thus, it is concluded that, once the epileptogenic focus is identified by the
      video/EEG monitoring, then MEG is superior to EEG in order to precisely localize
      the current source of the interictal epileptic discharge. Another question often
      addressed is whether MEG can replace the invasive intracranial EEG recording or
      not. In addition to the above-described factors, different coverage of the
      cortical areas by MEG vs. invasive intracranial EEG recording has to be taken
      into account to explain some of the recent reports related to this question. MEG
      can be effectively applied to the investigation of cortical functions near the
      epileptogenic focus. It is especially so when combined with other non-invasive
      studies like functional magnetic resonance imaging (fMRI). In addition to the
      source analysis of magnetic fields related to various events or tasks, analysis
      of the task-related change of rhythmic cortical oscillations is a useful tool for
      studying higher cortical functions such as language in the presurgical
      evaluation.

PMID- 17452008
TI  - Neurophysiological indices of attention to speech in children with specific
      language impairment.
AB  - OBJECTIVE: The aim was to determine whether children with specific language
      impairment (SLI) differed from children with typical language development (TLD)
      in their allocation of attention to speech sounds. METHODS: Event-related
      potentials were recorded to non-target speech sounds in two tasks (passive-watch
      a video and attend to target tones among speech sounds) in two experiments, one
      using 50-ms duration vowels and the second using 250-ms vowels. The difference in
      ERPs across tasks was examined in the latency range of the early negative
      difference wave (Nd) found in adults. Analyses of the data using selected
      superior and inferior sites were compared to those using electrical field power
      (i.e., global field power or GFP). The topography of the ERP at the maximum GFP
      was also examined. RESULTS: A negative difference, comparable to the adult Nd,
      was observed in the attend compared to the passive task for both types of
      analysis, suggesting allocation of attentional resources to processing the speech
      stimuli in the attend task. Children with TLD also showed greater negativity than
      those with SLI in the passive task for the long vowels, suggesting that they
      allocated more attentional resources to processing the speech in this task than
      the SLI group. This effect was only significant using the GFP analysis and was
      seen as smaller GFP for the TLD than SLI group. The SLI group also showed
      significantly later latency than the TLD group in reaching the maximum GFP. In
      addition, a significantly greater proportion of children with SLI compared to
      those with typical language showed left-greater-than-right frontocentral
      amplitude at the latency determined from each child's maximum GFP peak.
      CONCLUSIONS: Children generally showed greater attention to speech sounds when
      attention is directed to the auditory modality compared to the visual modality.
      However, children with TLD, unlike SLI, also appear to devote some attentional
      resources to speech even in a task in which they are instructed to attend to
      visual information and ignore the speech. SIGNIFICANCE: These findings suggest
      that children with SLI have limited attentional resources, that they are poorer
      at dividing attention, or that they are less automatic in allocating resources to
      speech compared to children with typically developing language skills.

PMID- 17452009
TI  - Focal epileptiform activity described by a large computerised EEG database.
AB  - OBJECTIVE: To study the age-related topographical tendency of expressing
      epileptiform activity, and the effect of focal epileptiform activity (FEA) on the
      general cortical brain activity. METHODS: 1647 consecutive routine EEGs
      containing FEA were visually assessed for FEA location and asymmetry. Background
      activity was compared with that in normal EEGs from 3268 drug-free outpatient
      controls. RESULTS: FEA localisation was age-related (p<0.0005) except for the
      temporal region (p=0.22) where FEA was found equally often in the young and the
      old. The left hemisphere was more prone to FEA (p=0.018). The left-right
      asymmetry varied by age (p=0.013). FEA asymmetry occurred most frequently in EEGs
      from patients older than 80 years, and least frequent in the age-group 20-39
      years. FEA was associated with lower alpha rhythm (AR) frequencies (p=0.0041) and
      higher AR amplitudes (p=0.0023), as well as higher general background activity
      (GBA) amplitude (p<0.0005), while GBA frequencies were the same (p=0.96).
      CONCLUSIONS: Topographical localisation of FEA was age-dependent. There was an
      overall left dominance, but the side asymmetry was modest and varied by age. FEA
      was associated with changes in AR and GBA. SIGNIFICANCE: The results demonstrate
      that FEA is associated with cerebral cortical dysfunction also distant from the
      epileptic focus.

PMID- 17452010
TI  - Changes in measures of motor axon excitability with age.
AB  - OBJECTIVE: Threshold tracking is a novel technique that permits examination of
      the excitability of human axons in vivo. Protocols have been validated for
      sensory and motor axons, but there are limited data on the changes in the
      excitability of motor axons with age. This study aimed to determine such changes
      from the third to the eighth decades. METHODS: Sixty healthy subjects aged 22-79,
      10 per decade, were studied using the TRONDXM4 protocol of the QTRAC threshold
      tracking program to assess motor axon function. The median nerve was stimulated
      at the wrist and the compound muscle action potential was recorded from the
      thenar muscles. RESULTS: There was an increase in threshold in elderly subjects,
      associated with a decrease in slope of the stimulus-response curves. Strength
      duration time constant and threshold electrotonus to depolarising and
      hyperpolarising currents of up to 40% did not change significantly with aging.
      The current-threshold relationship was similar across all decades for
      subthreshold depolarising currents, but the slope of the current-threshold
      relationship was significantly steeper the older the subjects for hyperpolarising
      currents, particularly those greater than 40% of threshold. There was also a
      significant decrease in supernormality in the recovery cycle with increasing age.
      CONCLUSIONS: The threshold of axons increases with age and the extent of
      supernormality decreases. There may also be greater inward rectification in motor
      axons, perhaps due to greater activity of I(H), the hyperpolarisation-activated
      conductance, though this is only significant with hyperpolarising currents
      greater than 40% of the threshold current. SIGNIFICANCE: Many indices of axonal
      excitability, such as strength-duration time constant, the relative refractory
      period, late subnormality, threshold electrotonus and the depolarising side of
      the current-threshold relationship, do not change significantly with age. For
      other indices, age-related changes may be due to a combination of non-neural
      factors that alter current access to the node of Ranvier, changes in the axon and
      its myelination and, possibly, changes in channel activity and/or changes in
      extracellular [K(+)](o).

PMID- 17452011
TI  - Impaired rapid modulation of cerebral hemodynamics during a planning task in
      schizophrenia.
AB  - OBJECTIVE: Patients with schizophrenia show deficits in planning, and the
      Stockings of Cambridge (SOC) is a task that assesses planning performance. This
      study was undertaken to investigate rapid changes of cerebral hemodynamics during
      separate phases of SOC in schizophrenia and normals by means of functional
      transcranial Doppler sonography (fTCD). METHODS: We included 21 patients with
      chronic schizophrenia and a control group of 20 healthy subjects in the study.
      They underwent fTCD of the middle (MCA) and anterior cerebral arteries (ACA)
      during performance of SOC. RESULTS: The main finding was that healthy subjects
      significantly modulated the early cerebral hemodynamic response along distinct
      conditions of SOC, whereas we observed no significant differences in patients.
      Normally, there was an up-regulation of cerebral hemodynamics during mental
      planning, and about zero values were observed during movement execution. Patients
      showed lower development of the early cerebral hemodynamic response during
      planning of SOC. CONCLUSIONS: The findings of this study suggest a uniform
      pattern of cerebral hemodynamic regulation during a planning task in
      schizophrenia, whereas healthy subjects modulated such a response along a
      planning-movement execution sequence. SIGNIFICANCE: We provide novel evidence
      that modulation of cerebral hemodynamics is compromised in schizophrenia, and
      that fTCD constitutes a proper method to measure these alterations.

PMID- 17452012
TI  - No effect of DC brain polarization on verbal fluency in patients with advanced
      frontotemporal dementia.

PMID- 17452013
TI  - Median-radial sensory nerve comparative studies in the detection of median
      neuropathy at the wrist in diabetic patients.
AB  - OBJECTIVE: Median-ulnar comparative studies (MUCS) play an important role in the
      electrodiagnosis of carpal tunnel syndrome, but in diabetes concomitant
      involvement of Guyon's canal (ulnar nerve compression at the wrist) would reduce
      the sensitivity of MUCS. This study tested the utility of median-radial
      comparative studies (MRCS) in diabetic patients. METHODS: Anti-dromic MUCS and
      MRCS were prospectively performed in 120 patients with diabetes, and 64 normal
      controls. In 28 diabetic patients, latent addition using threshold tracking was
      performed in superficial radial sensory axons to estimate persistent nodal sodium
      currents. RESULTS: MUCS was abnormal in 49% of the diabetic patients, and MRCS
      was abnormal in 58%. Median motor distal latencies were prolonged in 38%, and
      median sensory nerve conduction velocities were slowed in 40%. The longer latency
      differences in MRCS were associated with smaller persistent sodium currents,
      suggesting that intra-axonal sodium accumulation mediated by hyperglycemia
      enhances nerve compression. CONCLUSIONS: MRCS appears to be the most sensitive
      electrodiagnostic test in the detection of median neuropathy at the wrist in
      diabetic patients. Nerve conduction slowing across the carpal tunnel may be
      associated with metabolic abnormalities under hyperglycemia. SIGNIFICANCE:
      Assessment of nerve conduction across the common entrapment sites could provide
      new insights into the pathophysiology of diabetic neuropathy related to metabolic
      factors.

PMID- 17452014
TI  - The physicochemistry of endotoxins in relation to bioactivity.
AB  - It is generally accepted that the interaction of bacterial pathogenicity factors
      such as endotoxin (lipopolysaccharide, LPS) with molecules and cells of the human
      immune system, which eventually may lead to pathophysiological effects like
      septic shock, is exerted by isolated molecules after their release from the
      bacteria. Therefore, the study of the direct, physical interaction of LPS with
      target structures by applying biophysical means is of high interest. The
      questions which arise in this context concern the biologically active unit of LPS
      (monomer, multimer, aggregate), the molecular conformation of the single
      molecules, the type of aggregation of LPS polymers, the strength of their binding
      to serum and membrane proteins and/or unspecific binding to membrane
      phospholipids. Here, recent progress is reviewed which has increased our
      understanding of the processes preceding LPS-induced immune cell activation.

PMID- 17452015
TI  - Expression and structural diversity of the lipopolysaccharide of Haemophilus
      influenzae: implication in virulence.
AB  - Lipopolysaccharide (LPS) is a major virulence determinant of the human bacterial
      pathogen Haemophilus influenzae. A characteristic feature of H. influenzae LPS is
      the extensive intra- and inter-strain heterogeneity of glycoform structure which
      is key to the role of the molecule in both commensal and disease-causing
      behaviour of the bacterium. Through the combination of genetics and detailed
      structural analyses, H. influenzae is an exemplar Gram-negative bacterium for
      which now the most extensive and detailed LPS structural data and functional
      correlates are available. LPS from H. influenzae consists of a conserved glucose
      substituted triheptosyl inner-core moiety l-alpha-d-Hepp-(1-->2)-[PEtn-->6]-l
      alpha-d-Hepp-(1-->3)-[beta-d-Glcp-(1-->4)]-l-alpha-d-Hepp linked to lipid A via
      Kdo 4-phosphate. The inner-core unit provides the template for attachment of
      oligosaccharide- and non-carbohydrate substituents. Here, the structure, genetics
      and expression of LPS glycoforms in the outer core are reviewed as well as their
      implication on virulence.

PMID- 17452016
TI  - The host response to endotoxin, antilipopolysaccharide strategies, and the
      management of severe sepsis.
AB  - Endotoxin, more accurately referred to as lipopolysaccharide (LPS), is recognized
      as the most potent microbial mediator implicated in the pathogenesis of sepsis
      and septic shock. Despite its discovery over one century ago, the fundamental
      role of endotoxin in most patients with septic shock remains enigmatic and its
      value as a target for therapeutic intervention continues to be a contentious
      clinical issue. LPS is viewed by the host as an alarm molecule indicating
      microbial invasion by gram-negative bacterial pathogens. The release of large
      quantities of LPS into the bloodstream is clearly deleterious to the host, and
      this event can precipitate the induction of a potentially lethal array of
      inflammatory mediators and procoagulant factors. The host response to highly
      purified LPS can create diffuse endothelial injury, tissue hypo-perfusion,
      disseminated intravascular coagulation, and refractory shock. Numerous attempts
      to block endotoxin activity in clinical trials with septic patients have met with
      inconsistent and largely negative results. The tremendous knowledge gained within
      the past decade into the precise molecular basis for LPS-mediated cellular
      activation and tissue injury has generated a new generation of therapies that
      specifically disrupt LPS signaling. This information should provide the necessary
      insights to specifically target anti-LPS interventions in the ongoing effort to
      improve the management of sepsis.

PMID- 17452017
TI  - The vascular therapist.
AB  - My association with John Uther began when I was appointed as his Cardiology
      Research Fellow at Royal Prince Alfred Hospital in 1976. In 1983 John (then the
      Head of the Cardiology Unit at Westmead Hospital) appointed me as a cardiologist.
      John Uther and David Cody did the first coronary angioplasty at Westmead Hospital
      in 1983. By the end of the 1980s all of the cardiologists were fully trained in
      angioplasty. The first coronary stent was deployed at Westmead Hospital in 1993.
      In the mid to late 1990s coronary artery stenting led to a higher rate of
      procedural success with reduction in early complications and late restenosis. By
      the late 1990s stenting became routine treatment for any coronary artery where a
      stent could be technically placed. Drug eluting stents were developed to further
      reduce the risk of restenosis and the first stent was deployed at Westmead in
      2002. We started primary coronary angioplasty in 1998 for patients presenting
      directly to Westmead Hospital with acute myocardial infarction. From November
      1999 this was expanded as we began transferring patients from peripheral
      hospitals within the Area Health Service. In 1996 we began performing non
      coronary artery angioplasty starting with carotid artery stenting followed by
      renal artery stenting in 1999. From early 2005 we have developed a collaboration
      with the vascular surgeons and we now perform a wide variety of non-coronary
      procedures as a team. In summary, vascular intervention has come a long way since
      John Uther did the first coronary procedure at Westmead Hospital 24 years ago.

PMID- 17452018
TI  - mTOR Complex1-S6K1 signaling: at the crossroads of obesity, diabetes and cancer.
AB  - Recent studies demonstrate that the mammalian target of rapamycin (mTOR) and its
      effector, S6 kinase 1 (S6K1), lie at the crossroads of a nutrient-hormonal
      signaling network that is involved in specific pathological responses, including
      obesity, diabetes and cancer. mTOR exists in two complexes: mTOR Complex1, which
      is rapamycin-sensitive and phosphorylates S6K1 and initiation factor 4E binding
      proteins (4E-BPs), and mTOR Complex2, which is rapamycin-insensitive and
      phosphorylates protein kinase B (PKB, also known as Akt). Both mTOR complexes are
      stimulated by mitogens, but only mTOR Complex1 is under the control of nutrient
      and energy inputs. Thus, to orchestrate the control of homeostatic responses,
      mTOR Complex1 must integrate signals from distinct cues. Here, we review recent
      findings concerning the regulation and pathophysiology associated with mTOR
      Complex1 and S6K1.

PMID- 17452019
TI  - Prehospital delay, contributing aspects and responses to symptoms among Norwegian
      women and men with first time acute myocardial infarction.
AB  - BACKGROUND: In patients with acute myocardial infarction (AMI), the delay between
      the onset of symptoms and hospital admission is a critical factor in reducing
      morbidity and mortality. AIMS: To assess gender differences in prehospital delay
      among women and men with first time AMI, generate more knowledge about aspects
      influencing this delay and investigate responses to acute symptoms. METHODS AND
      RESULT: Of 738 eligible patients, 149 women and 384 men responded to a
      questionnaire (72%). Over half of both women and men waited over one hour before
      they called for medical assistance and more than half the patients had a total
      prehospital delay exceeding two hours. Rapid development of symptoms and symptoms
      matching expectations reduced, self medication and consulting the spouse
      increased patient delay in both genders. Calling the Emergency Medical Service
      (EMS) reduced and calling a general practitioner increased total prehospital
      delay in both genders. ST-ELEVATION: (STEMI), symptoms experienced as unbearable
      and attributed as cardiac reduced patient delay, and symptoms from the back,
      shoulders or between scapulae increased prehospital delay, only in men.
      CONCLUSION: How patients responded to symptoms had vital impact on prehospital
      delay among both genders, but the experience and interpretation of symptoms had
      more influence in men than in women.

PMID- 17452020
TI  - Comparison with manual registration reveals satisfactory completeness and
      efficiency of a computerized cancer registration system.
AB  - Automated software for cancer registration, called Open Registry and developed by
      ourselves was adopted by the Varese (population-based) Cancer Registry starting
      from 1997. Since the use of automated cancer registration is increasing, it is
      important to assess the quality and completeness of the automated data being
      produced. In this study, we assessed the completeness of the automatically
      generated data by comparison with a gold standard of all cases identified by
      manual and automatic systems for the year 1997 when the automated system was
      introduced, and the manual system was still in operation. We also evaluated the
      efficiency of the automated system. 5027 cases were generated automatically; 2959
      (59%) were accepted automatically and 2068 (41%) were flagged for manual
      checking. Sixty-nine cases (1.3%) were not recorded automatically, the most
      common reason (0.8%) being that the incidence record was dated 1998, even though
      the case was incident in 1997. A total of 98.7% of all cases found were picked up
      by the automated system. A completeness figure of 98.7% indicates that the
      automatic procedure is a valid alternative to manual methods for routine case
      generation. The fact that 59% of cases were registered automatically indicates
      that the system can speed up data production and enhance registry efficiency.

PMID- 17452021
TI  - User-centered semantic harmonization: a case study.
AB  - Semantic interoperability is one of the great challenges in biomedical
      informatics. Methods such as ontology alignment or use of metadata neither scale
      nor fundamentally alleviate semantic heterogeneity among information sources. In
      the context of the Cancer Biomedical Informatics Grid program, the Biomedical
      Research Integrated Domain Group (BRIDG) has been making an ambitious effort to
      harmonize existing information models for clinical research from a variety of
      sources and modeling agreed-upon semantics shared by the technical harmonization
      committee and the developers of these models. This paper provides some
      observations on this user-centered semantic harmonization effort and its inherent
      technical and social challenges. The authors also compare BRIDG with related
      efforts to achieve semantic interoperability in healthcare, including UMLS,
      InterMed, the Semantic Web, and the Ontology for Biomedical Investigations
      initiative. The BRIDG project demonstrates the feasibility of user-centered
      collaborative domain modeling as an approach to semantic harmonization, but also
      highlights a number of technology gaps in support of collaborative semantic
      harmonization that remain to be filled.

PMID- 17452022
TI  - Alcohol misuse after bariatric surgery: epiphenomenon or "Oprah" phenomenon?

PMID- 17452023
TI  - A high-resolution anatomical ontology of the developing murine genitourinary
      tract.
AB  - Cataloguing gene expression during development of the genitourinary tract will
      increase our understanding not only of this process but also of congenital
      defects and disease affecting this organ system. We have developed a high
      resolution ontology with which to describe the subcompartments of the developing
      murine genitourinary tract. This ontology incorporates what can be defined
      histologically and begins to encompass other structures and cell types already
      identified at the molecular level. The ontology is being used to annotate in situ
      hybridisation data generated as part of the Genitourinary Development Molecular
      Anatomy Project (GUDMAP), a publicly available data resource on gene and protein
      expression during genitourinary development. The GUDMAP ontology encompasses
      Theiler stage (TS) 17-27 of development as well as the sexually mature adult. It
      has been written as a partonomic, text-based, hierarchical ontology that, for the
      embryological stages, has been developed as a high-resolution expansion of the
      existing Edinburgh Mouse Atlas Project (EMAP) ontology. It also includes group
      terms for well-characterised structural and/or functional units comprising
      several sub-structures, such as the nephron and juxtaglomerular complex. Each
      term has been assigned a unique identification number. Synonyms have been used to
      improve the success of query searching and maintain wherever possible existing
      EMAP terms relating to this organ system. We describe here the principles and
      structure of the ontology and provide representative diagrammatic, histological,
      and whole mount and section RNA in situ hybridisation images to clarify the terms
      used within the ontology. Visual examples of how terms appear in different
      specimen types are also provided.

PMID- 17452024
TI  - Aging-related occurrence in Ashkenazi Jews of leukocyte heteroplasmic mtDNA
      mutation adjacent to replication origin frequently remodeled in Italian
      centenarians.
AB  - Our previous observation that a mitochondrial DNA (mtDNA) homoplasmic C150T
      transition adjacent to the heavy strand replication origin at position 151 is
      greatly increased in frequency in Italian centenarians, as compared to the rest
      of the population, has prompted us to analyze a genetically distinct population
      to determine how robust the association of the C150T mutation with longevity is.
      In particular, we have analyzed leukocyte mtDNA from three groups of an Ashkenazi
      Jew population, namely, a large number (124) of female centenarians and near
      centenarians (95-108 years-old), their mixed gender offspring, and mixed gender
      control subjects. This analysis revealed a very low incidence of the C150T
      transition in the probands and the other two groups, and by contrast, the fairly
      high frequency of a homoplasmic T152C transition and of a homoplasmic T195C
      transition in all three groups of subjects. Furthermore, most significantly, an
      aging-related increase in incidence of the heteroplasmic T152C transition,
      presumably resulting from somatic events, was demonstrated in the Ashkenazi Jews.
      The T152C transition was not associated with a change in the replication origin
      at position 151, unlike the C150T transition in the Italian centenarians.

PMID- 17452025
TI  - Neuroendocrine aging in birds: comparing lifespan differences and conserved
      mechanisms.
AB  - As more comparative data become available, it is clear that the process of aging
      has fundamental similarities across classes of vertebrates. Birds provide a
      fascinating collection of species because of the considerable range in
      reproductive lifespan and variation in reproductive strategies that often relate
      to lifespan. One fascinating aspect of the comparative biology of aging in
      different avian species is the conserved mechanisms that appear very similar to
      those observed in mammals. Despite marked differences in sexual differentiation
      and reproductive function, including a single functional ovary and the internal
      testes, there appears to be remarkable similarity in elements of neuroendocrine
      aging and their end results. Furthermore, although beyond the scope of this
      review, the intense endocrine and energetic demands on many species of temperate
      zone birds for long migration and the accompanying seasonal alterations in
      endocrine responses add an additional layer of complexity in understanding aging.
      It is the purpose of this review to focus on neuroendocrine changes that
      accompany aging in a short-lived bird, with mention of some of the available data
      in field birds and long-lived species. Unfortunately, few neuroendocrine data are
      available for these long-lived avian species. It would be very interesting to
      determine if these long-lived birds somehow manage to delay the cascade of
      changes that contribute to the demise of metabolic and reproductive endocrine
      function. This review will also attempt to integrate the time-related events that
      occur in the responses of the hypothalamus and the gonads, especially relative to
      the neuroregulatory systems that have been implicated in the age-related decline
      in reproductive function. Finally, emerging areas of interest will be considered
      in the context of future research areas.

PMID- 17452026
TI  - Adults with cystic fibrosis report important and unmet needs for disease
      information.
AB  - BACKGROUND: The informational needs of the growing population of adults with
      cystic fibrosis (CF) have not been previously assessed. METHODS: Adults with CF
      enrolled in the Project on Adult Care in CF (PAC-CF) completed a survey including
      22 items in which information topics were rated on the importance of receiving
      more information and the satisfaction with sources of information. Unmet needs
      were defined as those topics rated with both high importance and low satisfaction
      with information sources. RESULTS: The median age of the 233 respondents was 34
      years, median FEV(1) was 68% predicted, and 59% were female. The information
      topics with the highest mean importance ratings were on CF treatments and
      managing infection. The percentage of respondents rating an individual
      information need as unmet ranged from 2-32%. Information on "ways to deal with
      decreased energy, "new CF therapies," and "ways to deal with the unpredictability
      of the future" were reported as unmet by almost one-third of respondents. For all
      but four of the information topics assessed, clinical and socio-demographic
      factors were not significantly associated with increased likelihood of reporting
      unmet informational needs. CONCLUSIONS: Adults with CF rated information on
      treatment topics as most important. In contrast, patients were more likely to
      report information needs on disease self-management and future planning as unmet.
      Clinical and socio-demographic patient characteristics were not systematically
      associated with unmet informational needs. Clinicians caring for adult CF
      patients should not solely rely socio-demographic factors or markers of disease
      severity as signals for providing comprehensive information on disease self
      management and future planning.

PMID- 17452027
TI  - Sensitive liquid chromatography/tandem mass spectrometry method for the
      determination of the lipophilic antipsychotic drug chlorpromazine in rat plasma
      and brain tissue.
AB  - A simple, sensitive and robust liquid chromatography/electrospray ionization
      tandem mass spectrometry (LC-ESI-MS/MS) method was developed and validated for
      quantification of chlorpromazine in rat plasma and brain tissue. Chlorpromazine
      was extracted from rat plasma and brain homogenate using liquid-liquid
      extraction. The compounds were separated on a Waters Atlantis dC-18 (30 mm x 2.1
      mm i.d., 3 microm) column using a mobile phase of acetonitrile/20 mM ammonium
      formate (pH 4.25 adjusted with formic acid) with gradient elution. Chlorpromazine
      was detected in positive ion mode using multiple reaction monitoring (MRM). The
      method was validated and the specificity, linearity, lower limit of quantitation
      (LLOQ), precision, accuracy, recoveries and stability were determined. The LLOQ
      was 0.2 ng/ml for plasma and 0.833 ng/g for brain tissue. The method was linear
      over the concentration range from 0.2 to 200.0 ng/ml for plasma and from 0.833 to
      833.3 ng/g for brain tissue. The correlation coefficient (R(2)) values were more
      than 0.998 for both plasma and brain homogenate. The precision and accuracy for
      intra-day and inter-day were better than 7.54%. The relative and absolute
      recovery was above 84.9% and matrix effects were lower than 5.6%. This validated
      method has been successfully used to quantify the rat plasma and brain tissue
      concentration of chlorpromazine after chronic treatment.

PMID- 17452028
TI  - Simultaneous analysis of cytochrome P450 probes-dextromethorphan, flurbiprofen
      and midazolam and their major metabolites by HPLC-mass-spectrometry/fluorescence
      after single-step extraction from plasma.
AB  - Cytochrome P450 enzymes catalyze oxidative metabolism of most pharmaceutical
      compounds. Consequently dextromethorphan, flurbiprofen, midazolam and other
      compounds are commonly used as probe substrates to evaluate cytochrome P450
      function in humans. A "cocktail" approach employing simultaneous administration
      of two or more of the probe substrates has been used by various investigators in
      recent years. An analytical strategy to simultaneously extract and analyze
      dextromethorphan, flurbiprofen and midazolam and their major metabolites
      (dextrorphan, 4'-hydroxy-flurbiprofen and 1'-hydroxy-midazolam) by HPLC
      MS/fluorescence was developed and is described here. The three probe substrates
      and their major metabolites were extracted simultaneously by means of a solid
      phase (Bond Elut Certify cartridges) extraction procedure from 200 microl of pig
      plasma. The extraction efficiency was more than 79.5% for each of the six
      analytes. The extracted compounds were chromatographically separated on a Luna
      C8(II) column (50 mm Lx3 mm ID) in a single run of 20 min and analyzed by either
      fluorescence (flurbiprofen and 4'-hydroxy-flurbiprofen) or selective ion
      monitoring (dextromethorphan, dextrorphan, midazolam and 1'-hydroxy-midazolam)
      with positive electrospray ionization. The limit of quantification was 2.5 ng/ml
      for midazolam and 5 ng/ml for the other five analytes. The assay was precise and
      accurate (error: -9.1 to 12.1) with total CVs of 13.9% or better for each of the
      6 analytes. This method was used to analyze concentrations of the three probes
      and their metabolites in plasma after intravenous administration to a healthy
      pig.

PMID- 17452029
TI  - Development and validation of a liquid chromatography/tandem mass spectrometry
      assay for the simultaneous determination of D-amphetamine and diphenhydramine in
      beagle dog plasma and its application to a pharmacokinetic study.
AB  - A new drug, quick-acting anti-motion capsule (QAAMC) composed of d-amphetamine
      sulfate, dimenhydrinate and ginger extraction has been studied for anti-motion
      sickness use. We have developed a sensitive, specific liquid chromatography
      tandem mass spectrometry (LC-MS/MS) for the quantitative determination of d
      amphetamine and diphenhydramine, the main effective components of the QAAMC,
      using pseudoephedrine as the internal standard. The analytes and internal
      standard were isolated from 200 microL plasma samples by a simple liquid-liquid
      extraction (LLE). Reverse-phase HPLC separation was accomplished on a Zorbax SB
      C18 column (100 mm x 3.0 mm, 3.5 microm) with a mobile phase composed of methanol
      water-formic acid (65:35:0.5, v/v/v) at a flow rate of 0.2 mL/min. The method had
      a chromatographic total run time of 5 min. A Varian 1200 L electrospray tandem
      mass spectrometer equipped with an electrospray ionization source was operated in
      selected reaction monitoring (SRM) mode with the precursor-to-product ion
      transitions m/z 136.0-->91.0 (D-amphetamine), 256.0-->167.0 (diphenhydramine) and
      166.1-->148.0 (IS) used for quantitation. The method was sensitive with a lower
      limit of quantitation (LLOQ) of 0.5 ng/mL for d-amphetamine and 1 ng/mL for
      diphenhydramine, with good linearity in the range 0.5-200 ng/mL for D-amphetamine
      and 1-500 ng/mL for diphenhydramine (r(2)> or =0.9990). All the validation data,
      such as accuracy, precision, and inter-day repeatability, were within the
      required limits. The method was successfully applied to pharmacokinetic study of
      the QAAMC in beagle dogs.

PMID- 17452030
TI  - Simultaneous determination of residual stilbenes and stilbene metabolites in
      animal tissue by liquid chromatography-tandem mass spectrometry.
AB  - A liquid chromatographic (LC)-tandem mass spectrometry (MS/MS) method was
      developed for simultaneous determination of stilbenes, diethylstilbestrol (DES),
      hexestrol (HEX), and dienoestrol (DEN) in animal tissue. Sample clean-up and
      analyte enrichment was performed by automated solid-phase extraction (ASPE) with
      a silica gel cartridge. Detection capabilities (CCbeta) related to the transition
      products of lowest abundance for the method were 0.04-0.45 ng g(-1) in tissue and
      were achieved using atmospheric pressure chemical ionization (APCI) in negative
      mode. The use of an internal standard in combination with the simplified sample
      preparation led to a sensitive and reliable analytical method. The recovery level
      of the method was 84-108% for DES and DEN between 0.5 and 5 ng g(-1), and 59-87%
      for HEX between 0.25 and 2.5 ng g(-1).

PMID- 17452031
TI  - Application of liquid chromatography-mass spectrometry to measure the
      concentrations and study the synthesis of short chain fatty acids following
      stable isotope infusions.
AB  - A new method involving zinc sulphate deproteinization was developed to study
      short chain fatty acids (SCFA) production in the colon and subsequent occurrence
      of SCFA in blood. SCFA were baseline separated in a 30 min cycle using ion
      exclusion chromatography and detected by mass spectrometry. Concentrations could
      be measured down to 10 microM and isotopomeric distributions could be assessed,
      enabling the conduction of tracer studies to study changes in SCFA synthesis. The
      applicability of the method was tested in an extensively characterized pig model
      yielding portal SCFA concentrations ranging from 70 microM (butyric acid) to 150
      microM (propionic acid) to 440 microM (acetic acid) prior to butyrate tracer
      infusion, reaching butyric acid isotopic steady state within 2 h.

PMID- 17452032
TI  - Pressure effects on the heat-induced aggregation of equine serum albumin by FT-IR
      spectroscopic study: Secondary structure, kinetic and thermodynamic properties.
AB  - Pressure can restrain the heat-induced aggregation and dissociate the heat
      induced aggregates. We investigated the aggregation-preventing pressure effect
      and the aggregates-dissociating pressure effect to characterize the heat-induced
      aggregation of equine serum albumin (ESA) by Fourier transform infrared
      spectroscopy. The results suggest that the alpha-helical structure collapses at
      the beginning of heat-induced aggregation, then the rearrangement of structure
      from partially unfolded structure to the intermolecular beta-sheet takes place
      through the activated state. We determined the activation volume for the heat
      induced aggregation (DeltaV( not equal)=+92+/-8 ml mol(-1)) and the partial molar
      volume difference between native state and heat-induced aggregates (DeltaV(N-
      >HA)=+32 ml mol(-1)). This positive partial molar volume difference suggests that
      the heat-induced aggregates have larger internal voids than the native structure.
      Moreover, the positive volume change implies that the formation of the
      intermolecular beta-sheet is unfavorable under high pressure. We also determined
      the free energy profile of ESA. This energy profile explains the restriction of
      the formation of heat-induced aggregates by pressure. These results explain the
      structural differences between heat-induced aggregates with intermolecular beta
      sheet and pressure-induced aggregates without intermolecular beta-sheet.

PMID- 17452033
TI  - Structural features of the ligand binding site on human complement protein
      C8gamma: a member of the lipocalin family.
AB  - Human C8 is one of five components of the cytolytic membrane attack complex of
      complement. It contains three subunits (C8alpha, C8beta, C8gamma) arranged as a
      disulfide-linked C8alpha-gamma heterodimer that is noncovalently associated with
      C8beta. C8gamma has the distinction of being the only lipocalin in the complement
      system. Lipocalins have a core beta-barrel structure forming a calyx with a
      binding site for a small hydrophobic ligand. A natural ligand for C8gamma has not
      been identified; however previous structural studies indicate C8gamma has a
      typical lipocalin fold that is suggestive of a ligand-binding capability. A
      distinctive feature of C8gamma is the division of its putative ligand binding
      pocket into a hydrophilic upper portion and a large hydrophobic lower cavity.
      Access to the latter is restricted by the close proximity of two tyrosine side
      chains (Y83 and Y131). In the present study, binding experiments were performed
      using lauric acid as a pseudoligand to investigate the potential accessibility of
      the lower cavity. The crystal structure of a C8gamma.laurate complex revealed
      that Y83 and Y131 can move to allow penetration of the hydrocarbon chain of
      laurate into the lower cavity. Introducing a Y83W mutation blocked access but had
      no effect on the ability of C8gamma to enhance C8 cytolytic activity. Together,
      these results indicate that the lower cavity in C8gamma could accommodate a
      ligand if such a ligand has a narrow hydrophobic moiety at one end. Entry of that
      moiety into the lower cavity would require movement of Y83 and Y131, which act as
      a gate at the cavity entrance.

PMID- 17452034
TI  - The coexistence of mitochondrial ND6 T14484C and 12S rRNA A1555G mutations in a
      Chinese family with Leber's hereditary optic neuropathy and hearing loss.
AB  - We report here the clinical, genetic and molecular characterization of one three
      generation Han Chinese family with Leber's hereditary optic neuropathy (LHON) and
      hearing loss. Four of 14 matrilineal relatives exhibited the moderate central
      vision loss at the average age of 12.5 years. Of these, one subject exhibited
      both LHON and mild hearing impairment. Sequence analysis of the complete
      mitochondrial genomes in the pedigree showed the presence of homoplasmic LHON
      associated ND6 T14484C mutation, deafness-associated 12S rRNA A1555 mutation and
      47 other variants belonging to Eastern Asian haplogroup H2. None of other
      mitochondrial variants was evolutionarily conserved and functional significance.
      Therefore, the coexistence of the A1555G mutation and T14484C mutations in this
      Chinese family indicate that the A1555G mutation may play a synergistic role in
      the phenotypic manifestation of LHON associated ND6 T14484C mutation. However,
      the incomplete penetrance of vision and hearing loss suggests the involvement of
      nuclear modifier genes and environmental factors in the phenotypic expression of
      these mtDNA mutations.

PMID- 17452036
TI  - The effect of using different types of periodic contact rate on the behaviour of
      infectious diseases: a simulation study.
AB  - This paper studies the effect of using different types of seasonally varying
      contact rate on the behaviour of the seasonally varying infectious diseases for
      an SEIR epidemic model. Our target is to investigate the long term behaviour of
      the system in response to changes in beta(1), the amplitude parameter of the
      seasonal contact rate, which is our bifurcation parameter. This amplitude
      parameter is used as a filter to plot the length in years of the period of the
      stable endemic periodic solution of the SEIR model. Another main aim of this
      simulation study is to explain how can the type of the contact rate affect the
      behaviour of the disease dynamics. The simulation results have indicated that
      using different functional forms of seasonally varying contact rate generates
      different patterns of solutions for each disease parameter set and type of
      contact rate. So prediction of the type of disease outbreaks depends on the form
      of contact rate. Thus it is important to determine which type of contact rate is
      more likely to match the actual dynamics of each disease. Also these results have
      shown how the dynamics of the disease depend on the amplitude of the seasonally
      varying contact rate. Apart from some of the results for measles with a
      sinusoidal periodic function the simulation results are original and give a clear
      and a much broader insight into the features of the dynamics of these diseases
      [D. Greenhalgh, I.A. Moneim, SIRS epidemic model and simulations using different
      types of seasonal contact rate, Syst. Anal. Modelling Simul. 43(5) (2003) 573
      600; I.A. Moneim, D. Greenhalgh, Threshold and stability results for an SIRS
      epidemic model with a general periodic vaccination strategy, J. Biol. Syst. 13(2)
      (2005), to appear].

PMID- 17452035
TI  - PGD2 metabolism in plasma: kinetics and relationship with bioactivity on DP1 and
      CRTH2 receptors.
AB  - Prostaglandin (PG)D(2), an important mediator in allergic diseases, is rapidly
      transformed in plasma to active metabolites that bind and activate two distinct
      receptors, DP1 and CRTH2. Since the rate of PGD(2) degradation and the
      bioactivity of the resulting metabolites are still unclear, the aim of our study
      was to analyze the kinetics and biological effects of PGD(2) metabolites formed
      in plasma. Eosinophil shape change was taken as a parameter of chemotactic
      activation mediated by CRTH2 whereas inhibition of platelet aggregation served as
      a measure of DP1 activity. PGD(2) was degraded in plasma with an apparent half
      life of approximately 30 min, accompanied by a loss of potency in inhibiting
      platelet aggregation as well as inducing eosinophil stimulation. Incubation of
      PGD(2) in plasma for 120 min caused an increase in the IC(50) for platelet
      aggregation by a factor of 6.5 and an increase of the EC(50) for eosinophil shape
      change by a factor of 7.2. However, tandem mass spectrometry analysis showed that
      incubation of PGD(2) in plasma for 120 min resulted in clearance of PGD(2) of
      more than 92%, which was mirrored by a continuous formation of Delta(12)-PGD(2)
      and Delta(12)-PGJ(2), whereas only small amounts of 15d-PGD(2) and 15d-PGJ(2)
      were detected. Interestingly, a rapid degradation of PGD(2) was also observed in
      serum, which was not prevented by pepsin digestion of serum preceding the
      addition of PGD(2). Therefore, despite extensive non-enzymatic metabolization of
      PGD(2) in plasma, its biological activity with respect to DP1 and CRTH2 is
      maintained through the formation of bioactive metabolites.

PMID- 17452037
TI  - A structural perspective on ClC channel and transporter function.
AB  - The ClC chloride channels and transporters constitute a large family of membrane
      proteins that is involved in a variety of physiological processes. All members
      share a conserved molecular architecture that consists of a complex transmembrane
      transport domain followed by a cytoplasmic domain. Despite the strong
      conservation, the family shows an unusually broad variety of functional behaviors
      as some members work as gated chloride channels and others as secondary active
      chloride transporters. The conservation in the structure and the functional
      resemblance of gating and coupled transport suggests a strong mechanistic
      relationship between these seemingly contradictory transport modes. The
      cytoplasmic domains constitute putative regulatory components that are ubiquitous
      in eukaryotic ClC family members and that in certain cases interact with
      nucleotides thus linking ion transport to nucleotide sensing by yet unknown
      mechanisms.

PMID- 17452038
TI  - Pharmacological inhibition of RhoA signaling prevents connective tissue growth
      factor induction in endothelial cells exposed to non-uniform shear stress.
AB  - Shear stress changes play an important role in atheroma formation. This study
      focussed on atherogenic protein expression under non-uniform shear stress and the
      pharmacological modulation of shear-related endothelial dysfunction. Bifurcating
      flow-through cell culture slides were used to expose HUVECs to steady laminar or
      non-uniform shear stress for 18 h at 10 dyn/cm(2). Protein expression was
      determined by immunofluorescence, and quantified using MetaVue software. Laminar
      shear stress resulted in cell alignment, reduced F-actin fibers, and significant
      induction of endothelial nitric oxide synthase expression. Under non-uniform
      shear stress at bifurcations, minor upregulation of adhesion molecules was
      observed. Connective tissue growth factor (CTGF) was significantly downregulated
      by laminar shear stress and induced in cells exposed to non-uniform shear stress.
      CTGF upregulation by non-uniform shear stress was RhoA-dependent, because it was
      almost completely inhibited in cells transfected with dominant negative RhoA-N19,
      and when cells were treated with 1 micromol/L simvastatin during flow. Pre
      incubation of HUVECs with inhibitors of Rho-associated kinase before exposure to
      flow significantly suppressed the CTGF induction in regions of non-uniform shear
      stress. In conclusion, non-uniform shear stress-dependent CTGF expression
      requires active RhoA and can be prevented pharmacologically. Interference with
      shear stress-induced protein expression may inhibit endothelial dysfunction in
      atheroprone vessel regions.

PMID- 17452039
TI  - Perdeuterated n-alkanes for improved data processing in thermal desorption gas
      chromatography/mass spectrometry I. Retention indices for identification.
AB  - The identification of organic compounds by GC/MS is useful in various areas such
      as fuel, indoor and outdoor air and flavour and fragrance applications. Multi
      compound mixtures often contain isomeric compounds which have similar mass
      spectra and sometimes cannot be unambiguously identified by library search alone.
      Retention indices can help with confirmation of identification if they are
      reproducible. Using perdeuterated n-alkanes as a reference series for calculation
      of retention indices in GC/MS has a clear benefit because of the distinctive ion
      trace of m/z 34. Thermal desorption is useful for analysis of volatile organic
      compounds (VOCs) in air after sampling on appropriate sorbent cartridges.
      Comparison of indices between three systems, consisting of a thermal desorption
      unit, a gas chromatograph and a mass spectrometer, showed good agreement for
      compounds with well-defined peaks, whereas retention times varied.

PMID- 17452040
TI  - Micellar electrokinetic chromatography method for the determination of several
      natural red dyestuff and lake pigments used in art work.
AB  - The identification of organic colorants used in artistic paintings is an
      important information source for reconstructing the working techniques found in a
      particular work and for defining a programme for the restoration and conservation
      of the painting. In this work, sodium dodecyl sulfate (SDS) was used as a
      surfactant in micellar electrokinetic chromatography (MEKC) for separating a
      broad range of red organic pigments, based on their colouring matters: madder
      (colouring matters: alizarin, quinizarin and purpurin), cochineal (colouring
      matter: carminic acid), red sandalwood (colouring matter: santalin), brazilwood
      (colouring matter: brazilin), lac dye (colouring matter: laccaic acid) and
      dragon's blood (colouring matter: dracorhodin). The running electrolyte used was
      20 mM borax (pH 9), containing 20 mM SDS and 10% acetonitrile as organic
      modifier. Separation was carried out by applying a +20 kV voltage at the
      injection end, 25 degrees C and 214 nm/254 nm as detection wavelengths. All
      colorants were separated within less than 13 min with a good baseline resolution.
      The method was applied to the analysis of paint samples obtained from the
      Diocesan Museum of Holy Art of Bilbao.

PMID- 17452041
TI  - Biphasic perimicrovillar membrane production following feeding by previously
      starved Dysdercus peruvianus (Hemiptera: Pyrrhocoridae).
AB  - The development of perimicrovillar membranes (PMM) from midgut cells of starved
      and fed Dysdercus peruvianus was studied by using scanning electron microscopy
      (SEM), transmission electron microscopy (TEM) and assays for specific enzymatic
      markers of the perimicrovillar membranes (alpha-glucosidase), perimicrovillar
      space (aminopeptidase) and microvillar membranes (beta-glucosidase). High
      activities of these enzymes were observed 6h post-feeding and significant
      production of membranes was observed at 30 h post-feeding. In the gut cells of
      starved insects, the rough endoplasmic reticulum was organized in concentric
      bundles, with a greater number of mitochondria in the cellular apex. The presence
      of electron dense double-membrane vesicles and the production of PMM were not
      observed in this condition. Thirty hours post-feeding, a disorganization of the
      rough endoplasmic reticulum was observed, and it was possible to see double
      membrane vesicles close to the cell apex. The membrane system formation was
      evident with a significant development of PMM in the midgut lumen. The luminal
      surface of the midgut during starvation and up to 48 h post-feeding was monitored
      using SEM. It was demonstrated that in the starved condition, the PMM was
      virtually absent from gut cells, except at the base of the microvilli. At 6h post
      feeding, the microvilli were already completely covered with PMM, but with a
      maximum of PMM formation seen at 30 h post-feeding. Signals of PMM degradation
      were observed 48 h after pulse feeding.

PMID- 17452042
TI  - Outside opportunities and costs incurred by others.
AB  - Descriptions of interactions between ants and their 'guests' serve to illustrate
      the thesis that Ewald's theory of the 'evolution of virulence' not only applies
      to interactions between micro-organisms causing infectious diseases and their
      hosts, but also to interactions between individuals belonging to differing
      species. For instance, the prediction is put forward and discussed that guests of
      army ants are, relative to guests of other species of ants, more often parasitic.
      A key variable in Ewald's theory is 'transmissibility'. It shows some resemblance
      to similar variables used in micro-economic theory and in Emerson's sociological
      Power-Dependence Relations theory. In this article, this variable is called
      'outside opportunities'. In an A-B relation, an outside opportunity for A is
      anything which constitutes an alternative to what B can provide. It is concluded
      that in A-B interactions, the more outside opportunities are available to A, the
      more costs are incurred by B. Differences and similarities between this idea and
      Game Theory are discussed.

PMID- 17452043
TI  - Do scale-free regulatory networks allow more expression than random ones?
AB  - In this paper, we compile the network of software packages with regulatory
      interactions (dependences and conflicts) from Debian GNU/Linux operating system
      and use it as an analogy for a gene regulatory network. Using a trace-back
      algorithm we assemble networks from the pool of packages with both scale-free
      (real data) and exponential (null model) topologies. We record the maximum number
      of packages that can be functionally installed in the system (i.e., the active
      network size). We show that scale-free regulatory networks allow a larger active
      network size than random ones. This result might have implications for the number
      of expressed genes at steady state. Small genomes with scale-free regulatory
      topologies could allow much more expression than large genomes with exponential
      topologies. This may have implications for the dynamics, robustness and evolution
      of genomes.

PMID- 17452044
TI  - Electrophysiological correlates of common-onset visual masking.
AB  - In common-onset visual masking (COVM) the target and the mask come into view
      simultaneously. Masking occurs when the mask remains on the screen for longer
      after deletion of the target. Enns and Di Lollo [Enns, J. T., & Di Lollo, V.
      (2000). What's new in visual masking? Trends in Cognitive Sciences, 4(9), 345
      352] have argued that this type of masking can be explained by re-entrant visual
      processing. In the present studies we used high-density event-related brain
      potentials (HD-ERP) to obtain neural evidence for re-entrant processing in COVM.
      In two experiments the participants' task was to indicate the presence or absence
      of a vertical bar situated at the lower part of a ring highlighted by the mask.
      The only difference between the experiments was the duration of the target: 13
      and 40 ms for the first and second experiment respectively. Behavioral results
      were consistent between experiments: COVM was stronger as a joint function of a
      large set size and longer trailing mask duration. Electrophysiological data from
      both studies revealed modulation of a posterior P2 component around 220 ms post
      stimulus onset associated with masking. Further, in the critical experimental
      condition we revealed a significant relation between the amplitude of the P2 and
      behavioural response accuracy. We hypothesize that this re-activation of early
      visual areas reflects re-entrant feedback from higher to lower visual areas,
      providing converging evidence for re-entrance as an explanation for COVM.

PMID- 17452045
TI  - Influence of inorganic nutrition on growth and PSP toxin production of
      Alexandrium minutum (Dinophyceae) from Cork Harbour, Ireland.
AB  - The physiological response of the PSP toxin producing dinoflagellate Alexandrium
      minutum isolated from the Irish coast was assessed after modulating the initial
      concentrations of nitrate and phosphate in batch cultures. The cell growth in
      cultures of strain CK.A02 was primarily controlled by nitrate availability. In
      all experiments, only gonyautoxins 2 and 3 (GTX2 and 3) were synthesized along
      the different growth phases, with GTX3 dominating ( approximately 80%) at all
      stages, making the GTX2-3 toxin profile a possible population marker of A.
      minutum in Cork Harbour. The cellular toxin quotas remained low and relatively
      stable at around 2 pg cell(-1), except when high N:P ratios were initially used
      for culture inoculations; in these conditions PSP toxins accumulated up to 14 pg
      cell(-1). Due to the composition of the toxin profile, the toxicity of strain
      CK.A02 was generally relatively low (from 1.1 to 1.7 pg STX eqcell(-1)) in
      comparison with strains from other geographic areas except when phosphate
      limiting culture conditions were applied (maximum of 12.5 pg STX eq cell(-1)).
      Results showed that sufficient soluble protein quotas were necessary to observe
      the intra-cellular accumulation of PSP toxins in phosphate limiting conditions,
      highlighting also the requirement of adequate nitrogen supplies. The possible
      existence of localized toxicity hot spots in the field, linked to the
      accumulation of PSP toxins within A. minutum cells as a metabolic response to
      adverse environmental conditions, could potentially increase risks for shellfish
      farming operations.

PMID- 17452046
TI  - Maturation of the sensitivity for luminance and contrast modulated patterns
      during development of normal and pathological human children.
AB  - Any object may contain at least two spatio-temporal components referred to as
      first- and second-order, respectively, defined by spatial-temporal luminance
      modulation or by contrast, texture or depth modulation. This study investigates
      form sensitivity of infants, normals, premature or strabismic. A two-alternative
      forced-choice preferential looking procedure was used in monocular and binocular
      condition. Maturation profile for both stimuli was similar in the control group.
      Strabismic infants showed a vertical offset in maturation, which affected the
      second-order more severely. The pre-term group showed a lag of second-order
      sensitivity. Our results underline differences between first- and second-order
      processing.

PMID- 17452047
TI  - On why decreasing protein synthesis can increase lifespan.
AB  - An explanation is offered for the increased lifespan of Caenorhabditis elegans
      when mRNA translation is inhibited due to loss of the initiation factor IFE-2
      [Hansen, M., Taubert, T., Crawford, D., Libina, N., Lee, S.-J., Kenyon, C., 2007.
      Lifespan extension by conditions that inhibit translation in Caenorhabditis
      elegans. Ageing Cell 6, 95-110; Pan, K.Z., Palter, J.E., Rogers, A.N., Olsen, A.,
      Chen, D., Lithgow, G.J., Kapahi, P., 2007. Inhibition of mRNA translation extends
      lifespan in Caenorhabditis elegans. Ageing Cell 6, 111-119; Syntichaki, P.,
      Troulinaki, K., Tavernarakis, N., 2007. eIF4E function in somatic cells modulates
      ageing in Caenorhabditis elegans. Nature 445, 922-926]. It is suggested that the
      general reduction of protein synthesis, due to the decreased frequency of mRNA
      translation, also lowers the cellular load of erroneously synthesized
      polypeptides which the constitutive protein homeostatic apparatus (proteases and
      chaperones proteins) normally eliminates. This situation results in "spare"
      proteolytic and chaperone function which can then deal with those proteins
      modified post-synthetically, e.g. by oxidation and/or glycation, which are
      thought to contribute to the senescent phenotype. This increased availability of
      proteolytic and chaperone functions may thereby contribute to the observed
      increase in organism stress resistance and lifespan.

PMID- 17452048
TI  - Interaction between season and culture with insulin-like growth factor-1 on
      survival of in vitro produced embryos following transfer to lactating dairy cows.
AB  - Culture of bovine embryos in the presence of insulin-like growth factor-1 (IGF-1)
      can increase pregnancy rates following transfer to heat-stressed, lactating dairy
      cows. The objective of the present experiment was to determine whether the effect
      of IGF-1 on post-transfer embryo survival was a general effect or one specific to
      heat stress. Lactating recipients (n=311) were synchronized for timed-embryo
      transfer at four locations. Embryos were produced in vitro and cultured with or
      without 100 ng/mL IGF-1. At Day 7 after anticipated ovulation (Day 0), a single
      embryo was randomly transferred to each recipient. Pregnancy was diagnosed at Day
      21 by elevated plasma progesterone concentrations, at Days 27-32 by
      ultrasonography, and at Days 41-49 by transrectal palpation. Transfers were
      categorized into two seasons, hot or cool (based on the month of transfer). There
      was a tendency (P<0.09) for an interaction between embryo treatment and season
      for pregnancy rate at Day 21; this interaction was significant at Days 30 and 45
      (P<0.02). Recipients receiving IGF-1 treated embryos had higher pregnancy rates
      in the hot season but not in the cool season. There was a similar interaction
      between embryo treatment and season for overall calving rate (P<0.05). There was
      also an interaction between season and treatment affecting pregnancy loss between
      Days 21 and 30; recipients that received IGF-1 treated embryos had less pregnancy
      loss during this time period in the hot season but not in the cool season. The
      overall proportion of male calves born was 77.5%. In conclusion, treatment of
      embryos with IGF-1 improved pregnancy and calving rates following the transfer of
      in vitro produced embryos into lactating recipients, but only under heat-stress
      conditions.

PMID- 17452049
TI  - Role of the oviduct in sperm capacitation.
AB  - Following insemination of spermatozoa pre-ovulation, the mammalian oviduct
      ensures, by the formation of a functional sperm reservoir (SR), that suitable
      (low) numbers of viable and potentially fertile spermatozoa are available for
      fertilization at the ampullary isthmic junction (AIJ). As ovulation approaches, a
      proportion of the SR-stored spermatozoa is continuously distributed towards the
      AIJ and individually activated leading to step-wise capacitation and the
      attainment of hyperactivated motility. This paper reviews in vivo changes in the
      intra-luminal milieu of the oviduct of pigs and cows, in particular the SR and
      the AIJ which relate to the modulation of sperm capacitation around spontaneous
      ovulation. In vivo, most viable spermatozoa in the pre-ovulatory SR are
      uncapacitated. Capacitation rates significantly increase after ovulation,
      apparently not massively but concurrent with the individual, continuous sperm
      dislocation from the SR. Bicarbonate, whose levels differ between the SR and the
      AIJ, appears as the common primary effector of the membrane destabilizing changes
      that encompasses the first stages of capacitation. Sperm activation can be
      delayed or even reversed by co-incubation with membrane proteins of the tubal
      lining, isthmic fluid or specific tubal glycosaminoglycans, such as hyaluronan.
      Although the pattern of response to in vitro induction of sperm activation -
      capacitation in particular - is similar for all spermatozoa, the capacity and
      speed of the response is very individual. Such diversity in responsiveness among
      spermatozoa insures full sperm viability before ovulation and the presence of
      spermatozoa at different stages of capacitation at the AIJ, thus maximizing the
      chances of normal fertilization.

PMID- 17452050
TI  - Changes in numbers of large ovarian follicles, plasma luteinizing hormone and
      estradiol-17beta concentrations and egg production figures in farmed ostriches
      throughout the year.
AB  - In this study we described and analysed changes in the numbers of large ovarian
      follicles (diameter 6.1-9.0 cm) and in the plasma concentrations of luteinizing
      hormone (LH) and estradiol-17beta (E(2)beta) in relation to individual egg
      production figures of farmed ostriches (Struthio camelus spp.) throughout one
      year. Ultrasound scanning and blood sampling for plasma hormone analysis were
      performed in 9 hens on a monthly basis during the breeding season and in two
      periods of the non-breeding season. Our data demonstrated that: (1) large
      follicles were detected and LH concentrations were elevated already 1 month
      before first ovipositions of the egg production season took place; (2) E(2)beta
      concentrations increased as soon as the egg production season started; (3)
      numbers of large follicles, LH and E(2)beta concentrations were elevated during
      the entire egg production season; and that (4) numbers of large follicles, LH and
      E(2)beta concentrations decreased simultaneous with or following the last
      ovipositions of the egg production season. By comparing these parameters during
      the egg production season with their pre-and post-seasonal values, significant
      differences were found in the numbers of large follicles and E(2)beta
      concentrations between the pre-seasonal, seasonal and post-seasonal period; while
      LH concentrations were significantly different between the seasonal and post
      seasonal period. In conclusion, our data demonstrate that changes in numbers of
      large follicles and in concentrations of LH and E(2)beta closely parallel
      individual egg production figures and provide some new cues that egg production
      in ostriches is confined to a marked reproductive season. Moreover, our data
      provide indications that mechanism, initiating, maintaining and terminating the
      egg production season in farmed breeding ostriches are quite similar to those
      already known for other seasonal breeding bird species.

PMID- 17452051
TI  - Antibodies to proteinase 3 prime human monocytic cells via protease-activated
      receptor-2 and NF-kappaB for Toll-like receptor- and NOD-dependent activation.
AB  - Anti-neutrophil cytoplasmic Abs against proteinase 3 (PR3) have been detected in
      relation to a wide range of inflammatory conditions, and the interaction of anti
      PR3 Abs with leukocytes provokes cell activation, although how is not clear. Flow
      cytometric analysis revealed an increase in cell-surface CD14, Toll-like receptor
      (TLR)2, TLR4 and intracellular TLR3, TLR7, TLR8, TLR9, NOD1 and NOD2 expression
      during anti-PR3 priming in human monocytic THP-1 cells. Anti-RP3 Abs markedly
      promoted the release of IL-8 induced by chemically synthesized TLR and NOD
      ligands mimicking bacterial components: TLR2-agonistic lipopeptide (FSL-1), TLR3
      agonistic poly I:C, TLR4-agonistic lipid A (LA-15-PP), TLR7/8-agonistic single
      stranded RNA (ssPolyU), TLR9-agonistic bacterial CpG DNA, NOD1-agonistic
      FK156/565 and NOD2-agonistic muramyldipeptide (MDP) in THP-1 cells and human
      peripheral blood mononuclear cells, although sole incubation with anti-PR3 Abs
      induced only a low level of IL-8. The priming response was evident after 2h of
      preincubation with anti-PR3 Abs and peaked after 6h. Priming was also observed
      for the production of TNF-alpha and monocyte chemoattractant protein-1. An RNA
      interference assay revealed that anti-PR3 Abs activated THP-1 cells in a PR3- and
      protease-activated receptor-2-dependent manner. Furthermore, the anti-PR3 Ab
      mediated cell activation was significantly abolished by RNA interference targeted
      at PR3 mRNA and by inhibition of phospholipase C and NF-kappaB. These results
      suggest that anti-PR3 Abs prime human monocytic cells to produce cytokines upon
      stimulation with various bacterial components by up-regulating the TLR and NOD
      signaling pathway, and that these mechanisms may actively participate in the
      inflammatory process.

PMID- 17452052
TI  - Use of sodium hypochlorite (NaOCl) in laundering stops cross-contamination of
      Bacillus cereus.

PMID- 17452053
TI  - Identification of the neuropeptide content of individual rat neurohypophysial
      terminals.
AB  - The objective of this study was to develop a method that could reliably determine
      the arginine vasopressin (AVP) and/or oxytocin (OT) content of individual rat
      neurohypophysial terminals (NHT) >or=5 microm in diameter, the size used for
      electrophysiological recordings. We used a commercially available, highly
      sensitive enzyme-linked immunoassay (ELISA) kit with a sensitivity of 0.25 pg to
      AVP and of 1.0pg to OT. The NHT content of AVP (2.21+/-0.10 pg) was greater than
      OT (1.77+/-0.08 pg) and increased with terminal size. AVP-positive terminals
      (10.2+/-0.21 microm) were larger in diameter than OT-positive terminals (9.1+/
      0.24 microm). Immunocytochemical techniques indicated that a higher percentage
      (58%) of smaller terminals contained OT, and that a higher percentage (42%) of
      larger NHTs were colabeled. Similar percentages of AVP-positive terminals were
      obtained between immunocytochemical (73%) and ELISA (72%) methods when NHTs were
      assayed for AVP alone, but there was a higher percentage of OT terminals when
      using immunocytochemistry (43%) compared to ELISA (26%). The percent of AVP
      positive (60%) and OT-positive (18%) terminals decreased when NHT were assayed
      for both AVP and OT. Therefore, the best method to reliably identify AVP-positive
      NHTs is to assay only for AVP, since this allows the conclusion that AVP-negative
      terminals contain only OT.

PMID- 17452054
TI  - The effect of age on the dynamics and the level of c-Fos activation in response
      to acute restraint in Lewis rats.
AB  - Recent studies have reported an age-related increase of anxiety in rodents with a
      concomitant decrease in neuronal activity in some of the key structures of the
      fear/anxiety circuit. In the present study we present evidence that distinct
      parts of this circuit are differentially affected by age in Lewis rats. The
      effect of ageing is observed both at the actual level of neuronal activation and
      its time-course. While the structures belonging to the HPA axis react with a
      bigger neuronal activation and almost no change in the shape of dynamics curve in
      response to restraint, the structures involved in higher processing of emotional
      cues (amygdala and hippocampus) become deficiently activated with age despite
      their generally higher basal level of activation.

PMID- 17452056
TI  - Effect of nutrient availability on the uptake of PCB congener 2,2',6,6'
      tetrachlorobiphenyl by a diatom (Stephanodiscus minutulus) and transfer to a
      zooplankton (Daphnia pulicaria).
AB  - The objective of this study was to examine the importance of nutrient status of a
      diatom (Stephanodiscus minutulus) to the uptake of PCB congener #54 (2,2',6,6'
      tetrachlorobiphenyl) and the subsequent transfer of PCB to a pelagic grazing
      zooplankton (Daphnia pulicaria). The algae, which were grown under different
      nutrient treatments, were then fed to a zooplankton to examine the subsequent
      food chain transfer of PCB. Algal cultures were grown for at least 2 weeks in a
      steady state condition in (1) non-limiting, (2) low-Si, (3) low-N or (4) low-P
      media. Steady state algal cultures were dosed with 0.2 microg L(-1) PCB and were
      sampled for PCB uptake after 24h. D. pulicaria were allowed to graze on these
      same cultures for 48 h before being analyzed for PCB body burdens. Low-Si (68% or
      0.135 microg L(-1) of PCB) and low-P cultures (62%) had significantly higher
      percentage uptake of total PCB than the non-limiting (55%) or low-N (52%)
      treatments. When these values were divided by biochemical or elemental
      parameters, PCB per lipids (microg microg(-1)) had one of the lowest coefficients
      of variation (CV) across the four treatments, indicating their importance in PCB
      uptake. When equal biovolumes of the four different treatment cultures were fed
      to zooplankton, both the low-N (13.9 ng PCB mg wet weight(-1)) and the low-P (9.6
      ng PCB mg wet weight(-1)) grazing D. pulicaria had significantly higher PCB per
      wet weight than the low-Si (5.6 ng PCB mg wet weight(-1)) and non-limited (2.6 ng
      PCB mg wet weight(-1)) grazing D. pulicaria. There were no significant
      differences between algal nutrient treatments in PCB per wet weight of
      zooplankton grazing on clean algal food in PCB contaminated media. This study
      indicates that uptake of PCB by phytoplankton can be significantly altered by
      nutrient availability which subsequently affects transfer to zooplankton,
      potentially through such responses as grazing rate and lipid assimilation.

PMID- 17452055
TI  - Social defeat, a paradigm of depression in rats that elicits 22-kHz
      vocalizations, preferentially activates the cholinergic signaling pathway in the
      periaqueductal gray.
AB  - Gene expression profiles in the periaqueductal gray (PAG) of adult Long-Evans
      rats as a function of a stressful social defeat in inter-male fighting encounters
      were examined. This social subordination model mimics prototypical behavioral
      changes that parallel aspects of clinical depression, has been postulated to
      simulate early changes in the onset of depression in the losers, and has been
      successfully utilized for the evaluation of antidepressant activity. The 22-kHz
      ultrasonic vocalizations (USVs) have been shown to reflect negative emotional
      states akin to anxiety and depression. Social defeat is the most robust and
      reliable method of eliciting these calls. The PAG has been shown to be a key
      brain region for the generation of 22-kHz ultrasonic vocalizations, and 22-kHz
      USVs have been shown to be controlled by the mesolimbic cholinergic system. In
      this present study, we examined gene expression changes in the PAG of social
      subordinate rats compared to dominant rats that do not Exhibit 22-kHz USVs. We
      found that social defeat significantly altered the genes associated with
      cholinergic synaptic transmission in the PAG. The most robust of these were the
      increased expression of the beta2 subunit of the nicotinic acetylcholine receptor
      (CHRNB2) and the T subunit of acetylcholinesterase (ACHE) in the subordinate
      animals. These changes were corroborated by quantitative real-time polymerase
      chain reaction (qRT-PCR) and found to be exclusive to the PAG compared to seven
      other brain regions examined. These data suggest that cholinergic transmission in
      the PAG is involved in the generation of 22-kHz USVs and provide potential
      therapeutic targets for the treatment of affective disorders.

PMID- 17452057
TI  - New evaluations of redox regulating system in adipose tissue of obesity.
AB  - During the past several decades, the incidence of obesity has significantly
      increased worldwide. Enormous efforts have been devoted to understanding the
      molecular mechanisms underlying obesity and its related metabolic disorders such
      as type 2 diabetes, cardiovascular disease, atherosclerosis, and hypertension. It
      is now well-established that altered adipocyte metabolism in obese patients is
      closely associated with the induction of various metabolic stresses including
      hyperglycemia, hyperlipidemia, hyperinsulinemia, and chronic inflammation.
      However, the cellular factor(s) which sense metabolic changes and/or initiate the
      pathological progression of obesity-induced metabolic disorders remain to be
      elucidated. In this review, we will discuss the possible roles of cellular
      NADP(+)/NADPH, which function as redox potential regulators, in the induction of
      obesity-associated oxidative stress, chronic inflammation, and insulin resistance
      and suggest G6PD, a NADPH-generating enzyme, as a novel target for treating
      metabolic disorders.

PMID- 17452058
TI  - Role of AMP-activated protein kinase in exercise capacity, whole body glucose
      homeostasis, and glucose transport in skeletal muscle -insight from analysis of a
      transgenic mouse model-.
AB  - To examine the role of muscle AMP-activated protein kinase (AMPK) in maximal
      exercise capacity, whole body glucose homeostasis, and glucose transport in
      skeletal muscle, we generated muscle-specific transgenic mice carrying cDNAs of
      inactive AMPK alpha2 (alpha2i TG). Fed blood glucose was slightly higher in
      alpha2i TG mice compared to wild type littermates, however, the difference was
      not statistically significant. In alpha2i TG mice, glucose tolerance was slightly
      impaired in male, but not in female mice, compared to wild type littermates.
      Maximal exercise capacity was dramatically reduced in alpha2i TG mice, suggesting
      that AMPK alpha2 has a critical role in skeletal muscle during exercise. We
      confirmed that known insulin-independent stimuli of glucose transport including
      mitochondrial respiration inhibition, hyperosmolarity, and muscle contraction
      increased both AMPK alpha1 and alpha2 activities in isolated EDL muscle in wild
      type mice. While, alpha2 activation was severely blunted and alpha1 activation
      was only slightly reduced in alpha2i TG mice by these insulin independent stimuli
      compared to wild type mice. Mitochondrial respiration inhibition-induced glucose
      transport was fully inhibited in isolated EDL muscles in alpha2i TG mice.
      However, contraction- or hyperosmolarity-induced glucose transport was nearly
      normal. These results suggest that AMPK alpha2 activation is essential for some,
      but not all insulin-independent glucose transport.

PMID- 17452059
TI  - Genetics of type 1 diabetes in Asian and Caucasian populations.
AB  - Among candidate genes for type 1 diabetes, HLA, INS, CTLA4, PTPN22 and SUMO4 have
      been shown to be associated with the disease in Caucasian populations. To clarify
      the similarities and differences in the contribution of these genes to type 1
      diabetes between Asian and Caucasian populations, association of these genes with
      type 1 diabetes was studied in a large number of samples in Japanese and Korean
      populations. Class II HLA was strongly associated with type 1 diabetes in both
      Asian and Caucasian populations, but haplotypes associated with type 1 diabetes
      were markedly different due to difference in the presence and absence of
      haplotypes in each population. INS was consistently associated with type 1
      diabetes in both Japanese and Caucasian populations, but frequency of disease
      associated haplotype was markedly high in Japanese general population. CTLA4 was
      associated with type 1 diabetes only in a subset of patients with type 1 diabetes
      complicated with AITD in Japanese. A variant (R620W) of PTPN22 was associated
      with type 1 diabetes and other autoimmune diseases in Caucasians, but the variant
      was absent in Asians. SUMO4 was associated with type 1 diabetes in Asians, but
      not in Caucasian, suggesting a genetic heterogeneity among diverse ethnic groups.
      Trans-racial study with a large number of samples in both Asian and Caucasian
      populations will contribute to genetic dissection of type 1 diabetes and
      identification of causative variants.

PMID- 17452060
TI  - Impact of mitochondrial ROS production on diabetic vascular complications.
AB  - Vascular complications are the leading cause of morbidity and mortality in
      patients with diabetes. Four main molecular mechanisms have been implicated in
      glucose-mediated vascular disease. There are: glucose-induced activation of
      protein kinase C (PKC) isoforms; increased formation of glucose-derived advanced
      glycation end-products (AGE); increased glucose flux through the aldose reductase
      pathway; and increased production of reactive oxygen species (ROS). Here we
      demonstrate that hyperglycemia-induced production of ROS is abrogated by
      inhibitors of mitochondrial metabolism, or by overexpression of uncoupling
      protein-1 or manganese superoxide dismutase. Normalization of mitochondrial ROS
      production by each of these agents prevents glucose-induced activation of PKC,
      formation of AGE, and accumulation of sorbitol in bovine vascular endothelial
      cells. We also claim that 8-hydroxydeoxyguanosine, which represents mitochondrial
      oxidative damage was elevated in patients with either retinopathy, albuminuria or
      increased intima-media thickness of carotid arteries. These results suggest that
      hyperglycemia induces mitochondrial ROS production, and which can associate to
      the pathogenesis of diabetic vascular complications.

PMID- 17452061
TI  - Up-regulation of PTEN at the transcriptional level is an adverse prognostic
      factor in female lung adenocarcinomas.
AB  - In lung adenocarcinomas, genetic alterations of PTEN are relatively rare and
      little has been reported concerning the relationship between PTEN transcriptional
      level and clinicopathologic features or genetic changes. This study was conducted
      to gain insight into clinicopathologic correlations. The transcriptional levels
      of PTEN were examined using real time RT-PCR and analyzed for correlations with
      clinicopathologic features and the mutation status of EGFR and KRAS. After
      confirming significant correlation for PTEN levels between macrodissected and
      microdissected materials (p<0.01), macrodissected samples from 115 lung
      adenocarcinomas were examined. There were no significant difference between the
      PTEN levels, divided into three ranges, and the mutation status of EGFR or KRAS.
      Noteworthy clinicopathologic correlations between PTEN transcriptional up/down
      regulation and young age (p=0.0081, 61.7+/-8.7years versus 66.1+/-8.1years),
      smoking (p=0.032) and less differentiated adenocarcinomas (p=0.013) were
      identified. Whereas male patients demonstrated no prognostic association with
      PTEN levels, female cases with up-regulated PTEN expression had significantly
      worse survival compared with those with normal PTEN levels (p=0.0027). This study
      revealed distinct clinicopathologic correlations with PTEN transcriptional
      up/down-regulation.

PMID- 17452063
TI  - Carbamoyl tetrazoles as inhibitors of endocannabinoid inactivation: a critical
      revisitation.
AB  - We have synthesized a series of 18 1,5- and 2,5-disubstituted carbamoyl
      tetrazoles, including LY2183240 (1) and LY2318912 (7), two compounds previously
      described as potent inhibitors of the cellular uptake of the endocannabinoid
      anandamide, and their regioisomers 2 and 8. We confirm that compound 1 is a
      potent inhibitor of both the cellular uptake and, like the other new compounds
      synthesized here, the enzymatic hydrolysis of anandamide. With the exception of
      9, 12, 15, and the 2,5-regioisomer of LY2183240 2, the other compounds were all
      found to be weakly active or inactive on anandamide uptake. Several compounds
      also inhibited the enzymatic hydrolysis of the other main endocannabinoid, 2
      arachidonoylglycerol, as well as its enzymatic release from sn-1-oleoyl-2
      arachidonoyl-glycerol, at submicromolar concentrations. Four of the novel
      compounds, i.e. 3, 4, 17, and 18, inhibited anandamide hydrolysis potently
      (IC50=2.1-5.4nM) and selectively over all the other targets tested (IC50 >or=
      10microM), thus representing new potentially useful tools for the inhibition of
      fatty acid amide hydrolase.

PMID- 17452064
TI  - Exploring molecular shape analysis of styrylquinoline derivatives as HIV-1
      integrase inhibitors.
AB  - HIV-1 integrase inhibitory activity data of styrylquinoline derivatives have been
      subjected to 3D-QSAR study by molecular shape analysis (MSA) technique using
      Cerius(2) version 4.8 software (Accelrys). For the selection of test set
      compounds, initially a QSAR analysis was done based on topological and structural
      descriptors and K-means clustering technique was used to classify the entire data
      set (n=36). Clusters were formed from the factor scores of the whole data set
      comprising of topological and structural descriptors without the biological
      activity, and based on the clusters, the data set was divided into training and
      test sets (n=26 and n=10, respectively) so that all clusters are properly
      represented in both training and test sets. In the molecular shape analysis, the
      major steps were (1) generation of conformers and energy minimization; (2)
      hypothesizing an active conformer (global minimum of the most active compound);
      (3) selecting a candidate shape reference compound (based on active
      conformation); (4) performing pair-wise molecular superimposition using maximum
      common subgroup [MCSG] method; (5) measuring molecular shape commonality using
      MSA descriptors; (6) determination of other molecular features by calculating
      spatial and conformational parameters; (7) selection of conformers; (8)
      generation of QSAR equations by standard statistical techniques. The best model
      obtained from stepwise regression and GFA techniques shows 51.6% predicted
      variance (leave-one-out) and 57.3% explained variance. In case of FA-PLS
      regression, the best relation shows 54.0% predicted variance and 57.9% explained
      variance. The R(2)(pred) and R(2)(test) values for the GFA derived model are
      0.611 and 0.664, respectively, while the best FA-PLS model has R(2)(pred) and
      R(2)(test) values of 0.602 and 0.656, respectively. These models show the
      importance of Jurs descriptors (total polar surface area, relative polar surface
      area, relative hydrophobic surface area, relative positive charge), fraction area
      of the molecular shadow in the XZ plane (ShadowXZfrac), common overlap steric
      volume and the ratio of common overlap steric volume to volume of individual
      molecules. Statistically reliable MSA models obtained from this study suggest
      that this technique could be useful to design potent HIV-1 integrase inhibitors.

PMID- 17452062
TI  - Longitudinal MRI findings from the vitamin E and donepezil treatment study for
      MCI.
AB  - The vitamin E and donepezil trial for the treatment of amnestic mild cognitive
      impairment (MCI) was conducted at 69 centers in North America; 24 centers
      participated in an MRI sub study. The objective of this study was to evaluate the
      effect of treatment on MRI atrophy rates; and validate rate measures from serial
      MRI as indicators of disease progression in multi center therapeutic trials for
      MCI. Annual percent change (APC) from baseline to follow-up was measured for
      hippocampus, entorhinal cortex, whole brain, and ventricle in the 131 subjects
      who remained in the treatment study and completed technically satisfactory
      baseline and follow-up scans. Although a non-significant trend toward slowing of
      hippocampal atrophy rates was seen in APOE is an element of 4 carriers treated
      with donepezil; no treatment effect was confirmed for any MRI measure in either
      treatment group. For each of the four brain atrophy rate measures, APCs were
      greater in subjects who converted to AD than non-converters, and were greater in
      APOE is an element of 4 carriers than non-carriers. MRI APCs and changes in
      cognitive test performance were uniformly correlated in the expected direction
      (all p<0.000). Results of this study support the feasibility of using MRI as an
      outcome measure of disease progression in multi center therapeutic trials for
      MCI.

PMID- 17452065
TI  - A discourse and Foucauldian analysis of nurses health beliefs: implications for
      nurse education.
AB  - AIMS OF STUDY: The aim of this study was to investigate nurses' constructions of
      health in order to determine what influence these have on their health education
      practices and their implications for nurse education. BACKGROUND: Burgeoning
      literature on health promotion claim that health promotion is central to nursing
      practice. This is a role that has grown in the context of a rapidly ageing
      population, emergence of new diseases and variants of old diseases, ecological
      and environmental concerns and apparent social fragmentation. Within the United
      Kingdom this has led to nurses being identified by agencies, such as the UK
      government, as having a leading role to play in what has become the 'holy grail'
      of patient lifestyle change. But this role has been based on the seemingly
      uncritical assumption that the UK nurse education system engenders the necessary
      knowledge, attitude and skills required by nurses for them to effectively promote
      lifestyle choices. This study draws upon discourse and Foucauldian social
      analysis to uncover, through nurses' narratives, how they construct health and
      enact their health education practices. METHODS: Twelve newly registered UK
      nurses were interviewed using hierarchical focused interviews. Data were analysed
      using discourse analysis. FINDINGS: The process of discourse analysis unearthed
      two opposing value positions held without any feeling of contradiction by
      respondents: a holistic view--the role-based/public account, and a victim blaming
      view--personal agency/private account. CONCLUSION: This dual set of values raises
      important concerns over the teaching of health promotion. Nurse education may
      need to revise its approach to health promotion by taking into account the power
      of private accounts of health promotion that prevail among some nurses.

PMID- 17452066
TI  - Palliative care and end of life issues in UK pre-registration, undergraduate
      nursing programmes.
AB  - Palliative and end of life care topics have traditionally not been in nursing
      school curricula. Only in recent years have these been included. The aim of this
      research was to determine the current status of such an emphasis in programmes in
      the United Kingdom (UK). A mailed survey in 2006 to the 66 undergraduate (pre
      registration) nursing programmes in the UK (return rate of 79%) determined that
      palliative and end of life care play a significant role in these programmes.
      Forty-five teaching hours on average were devoted to these topics. All of the
      schools have some provision on palliative and end of life care, and over 95% of
      students participated in these courses. A nurse was usually the primary
      instructor, although non-nurses were sometimes used. Attitudes toward dying and
      death and communicating with terminally-ill patients and family members were
      emphasised. By highlighting dying and death in the curricula, nursing schools
      appeared to be giving nursing students an opportunity to face the issue of death,
      thus helping them to be better prepared to help their patients and their families
      to do so.

PMID- 17452067
TI  - An in vitro biomechanical study comparing the spiral linking technique against
      the pulvertaft weave for tendon repair.
AB  - A new spiral linking technique for tendon repair in which one end of the tendon
      is spiralled around the other end has been developed. Using pig trotter extensor
      tendons, the Pulvertaft weave technique was compared with this new technique.
      Twenty-five repairs using each technique were tested by tensile loading with an
      Instron testing machine. The spiral linking technique matched the strength of
      Pulvertaft method: the mean peak loads were 102 and 105 N, respectively. The
      Pulvertaft weave was stiffer than the spiral linking technique: mean stiffness of
      11.1 and 6.7 N/mm, respectively. The spiral linking technique also absorbed
      considerably more energy: energy absorbed prior to failure to 90% of peak load,
      1.75 and 1.13 kN mm, respectively. In conclusion, the spiral linking technique
      appears as strong as the Pulvertaft weave and we believe it is easier to perform.

PMID- 17452068
TI  - Evaluation of M-AID, a first aid application for mobile phones.
AB  - BACKGROUND: When performed effectively, cardiopulmonary resuscitation (CPR) by
      bystanders reduces mortality due to sudden cardiac arrest. Telemedicine
      applications offer a means by which bystanders can get specific instructions for
      handling the emergency situation. M-AID, a first aid application for mobile
      phones, uses an intelligent algorithm of 'yes' or 'no' questions to judge the
      ongoing situation and give the user detailed instructions. The aim of this study
      was to evaluate the benefit of this mobile phone application in a scenario of
      sudden cardiac arrest. METHODS: One hundred and nineteen volunteers were assigned
      at random either to the test or the control group. All participants were
      confronted with the same scenario of acute coronary syndrome leading to cardiac
      arrest. The participants were either equipped with a mobile phone running the
      software (test group) or had to handle the situation without support (control
      group). The participants received a certain amount of credits for each action
      taken according to a pre-defined protocol and these credits were added to a score
      and compared between the groups. Participants were divided into subgroups
      according to their medical and technical experience. RESULTS: The test group
      generally achieved a slightly higher average score that was not statistically
      significant (21.11 versus 19.97; p=0.302). In contrast, the performance of the
      individuals in the control group was significantly faster (2.41 min versus 4.24
      min; p<0.001). Use of the mobile phone software did not enhance the chance of
      survival. Subgroup analysis showed that experienced mobile phone users performed
      significantly better than non-experienced individuals, but not as well as
      participants with advanced first aid knowledge. CONCLUSIONS: Experience in the
      use of mobile phones is a prerequisite for the efficient use of the tested M-AID
      version. This application cannot replace skills acquisition by practical
      training. In a subgroup with experience in mobile phone use and basic knowledge
      in CPR, the device improved performance of CPR.

PMID- 17452069
TI  - The relationship between shocks and survival in out-of-hospital cardiac arrest
      patients initially found in PEA or asystole.
AB  - OBJECTIVE: To describe survival rates from out-of-hospital cardiac arrest for
      patients who present with pulseless electrical activity or asystole according to
      whether they remained in a non-shockable rhythm or converted to ventricular
      fibrillation and were shocked appropriately. METHODS:  RESULTS: Observational
      analysis of a cardiac arrest registry collected as part of a randomized trial.
      SETTING: Five urban/suburban cities in the United States and Canada.
      PARTICIPANTS: Trial subjects (adult, treated, non-traumatic) whose first
      documented heart rhythm/state following cardiac arrest was asystole or pulseless
      electrical activity. INTERVENTION: Periodic pauses to assess for shockable
      rhythm. MAIN OUTCOME MEASURE: Survival to hospital discharge. RESULTS: Of 1377
      cardiac arrest patients, 738 presented with an initial arrest rhythm/state of
      either pulseless electrical activity or asystole. Of the 738, 78% (n=574)
      subsequently remained in a non-shockable rhythm/state at each evaluation
      throughout the resuscitation (No-Shock group) while 22% (n=164) converted to
      ventricular fibrillation and were shocked by emergency medical service (Shock
      group). Survival to hospital discharge was significantly greater in the No-Shock
      group (4.9% versus 0.6%, p=0.01). Shock group remained a predictor (odds
      ratios=0.18, p=0.036) of death after adjustment for potential confounders.
      CONCLUSIONS: These results suggest that patients with cardiac arrest who develop
      VF during the course of treatment for initially observed pulseless electrical
      activity or asystole do not benefit from conventional approaches to treatment
      such as defibrillation. Further study is warranted to define the optimal
      treatment of this patient cohort.

PMID- 17452070
TI  - Prospective, randomized trial of the effectiveness and retention of 30-min
      layperson training for cardiopulmonary resuscitation and automated external
      defibrillators: The American Airlines Study.
AB  - OBJECTIVE: A head-to-head trial was conducted to compare laypersons' long-term
      retention of life-saving psychomotor and cognitive skills learned in the
      traditional multi-hour training format for basic cardiopulmonary resuscitation
      and automated external defibrillator use to those learned in an abbreviated (30
      min) course. METHODS: Laypersons were randomized to either: (1) the traditional
      multi-hour Heartsaver-Automated External Defibrillator (Heartsaver-AED) group; or
      (2) the 30-min course group (cardiopulmonary resuscitation, choking, and
      automated external defibrillator use). Immediately after training, and at 6
      months, participants were provided identical individual testing scenarios. In
      addition to audio-video recordings, computerized recordings of compression
      rate/depth, ventilation rates, and related pauses were obtained and subsequently
      rated by blinded reviewers. RESULTS: Performance following 30-min training was
      either equivalent or superior (p<0.007) to the multi-hour Heartsaver-Automated
      External Defibrillator training in all measurements, both immediately and 6
      months after training. Although retention of certain skills deteriorated over the
      6 months among a significant number of participants from both groups, 84% of the
      30-min training group still was judged, overall, to perform cardiopulmonary
      resuscitation adequately. Moreover, 93% still were performing chest compressions
      adequately and 93% continued to apply the automated external defibrillator and
      deliver shocks correctly. CONCLUSIONS: Using innovative learning techniques, 30
      min cardiopulmonary resuscitation and automated external defibrillator training
      is as effective as traditional multi-hour courses, even after 6 months. Thirty
      minute courses should decrease labor intensity, demands on resources, and time
      commitments for cardiopulmonary resuscitation courses, thus facilitating more
      widespread and frequent retraining.

PMID- 17452071
TI  - A systematic review and quality assessment of systematic reviews of fetal
      fibronectin and transvaginal length for predicting preterm birth.
AB  - This systematic review aims to identify reviews of fetal fibronectin and
      transvaginal cervical length for predicting preterm birth, so that these could be
      appraised and the findings from good quality reviews highlighted. Reviews, rather
      than individual studies, are the basis for this systematic review because of the
      proliferation of reviews and the benefits of a single, consistent appraisal and
      assessment of evidence from these reviews, rather than further attempts to find
      and appraise the many individual studies in the literature. Potentially eligible
      reviews were sought primarily through searches of the electronic databases
      MEDLINE (1966-2005), EMBASE (1980-2005), CINHAL (1982-2005), Science Citation
      Index (1970-2005) and The Cochrane Library (Issue 3, 2005). Our systematic review
      consists of a description of the two factors that might be predictive of preterm
      birth and for which at least one relevant review was found. The scope and quality
      of the identified review(s) are described, and their conclusions and the strength
      of these conclusions discussed. Ten reviews were identified, of which seven were
      included in this systematic review of reviews. The quality of each review is
      assessed within the following domains; the extent of searching undertaken,
      description of study selection and inclusion criteria, comparability of included
      studies, assessment of publication bias, assessment of heterogeneity and conduct
      of sensitivity analyses. The reviews we identified show that cervicovaginal fetal
      fibronectin and transvaginal sonographic cervical length measurements are
      clinically useful factors in predicting preterm birth. Consideration might be
      given to the use of both the measurement of cervicovaginal fetal fibronectin and
      transvaginal sonographic assessment of cervical length to identify women at
      increased risk of preterm birth and, potentially, to improve the outcome for
      these women and their babies.

PMID- 17452073
TI  - Metabolic dysfunction and male pelvic health.

PMID- 17452074
TI  - Arsenate removal from water by an alumina-modified zeolite recovered from fly
      ash.
AB  - A cancrinite-type zeolite was synthesized from Class C fly ash by molten-salt
      method. The product (ZFA) was used as the adsorbent for the arsenate removal from
      water. The adsorption equilibriums of arsenate are investigated on various
      adsorbents. ZFA showed a higher adsorption capacity (5.1 mg g(-1)) than activated
      carbon (4.0 mg g(-1)), silica gel (0.46 mg g(-1)), zeolite NaY (1.4 mg g(-1)),
      and zeolite 5A (4.1 mg g(-1)). The relatively higher adsorption capacity of ZFA
      than zeolite NaY and 5A was attributed to the low Si/Al ratio and the mesoporous
      secondary pore structure of ZFA. However, it was found that the adsorption
      capacity of zeolites were generally lower than activated alumina (16.6 mg g(-1)),
      which is ascribed to the small pores in zeolite frameworks. The adsorption
      capacity of ZFA was significantly improved after loaded by alumina via a wet
      impregnation method. The modified ZFA (ZFA-Al(50)) with the optimum alumina
      loading showed an adsorption capacity of 34.5 mg g(-1), which was 2.1 times
      higher than activated alumina. The Toxicity Characteristic Leaching Procedure
      (TCLP) leachability tests indicated that the spent ZFA and alumina-modified ZFA
      complied with the EPA regulations for safe disposal.

PMID- 17452075
TI  - Characterization of dissolved organic matter in leachate discharged from final
      disposal sites which contained municipal solid waste incineration residues.
AB  - The properties of dissolved organic matter (DOM) in the leachates discharged from
      lysimeters and landfill sites containing municipal solid waste incineration
      residues (MSWIRs) were studied. DOM samples were divided into hydrophobic acid,
      base, neutral (Hpo-A, Hpo-B, Hpo-N) and hydrophilic (Hpi) fractions using the
      fractionation method employing DAX-8 resin. Hpi was the smallest fraction of all
      the raw leachate samples. The proportion of Hpo-N increased with increasing
      operating time. Landfill sites containing abundant non-combustible wastes showed
      a higher proportion of Hpo-B than Hpo-A. The molecular weights and functional
      groups of the DOM fractions were studied by using gel permeation chromatography
      and FTIR, respectively. In addition, the fluorescent properties and binding sites
      of the DOM fractions were investigated using fluorescence analysis. In the
      synchronous scan spectra of each DOM fraction, most of DOM fractions showed an
      emission peak for the main fluorophores at around 300 nm or 350 nm, which are
      regarded as aromatic amino acid-like fluorophores. The interaction between the
      DOM fraction and the pollutants (Cu(2+), pyrene and phenanthrene) was
      investigated using the fluorescence quenching method. It was observed that the
      aromatic amino acid-like fluorophores in the DOM fractions could be an important
      factor affecting complexation with the pollutants.

PMID- 17452076
TI  - Down-regulation of UNC5 homologue expression after the spinal cord injury in the
      adult rat.
AB  - UNC5A-D are transmembrane receptors for netrin that plays an important role in
      the development of the spinal cord. However, their function in the adult nervous
      system remains to be established. In the present study, the mRNA expression of
      UNC5 family was investigated in the adult rat spinal cord following a dorsal
      hemisection injury. Reverse transcription-polymerase chain reaction (RT-PCR)
      revealed that mRNA expression of rat UNC5 family was down-regulated in the spinal
      cord within 3 days after the dorsal hemisection. Unc5b-d mRNA expressions
      returned to near normal level after a week, whereas the down-regulation of Unc5a
      mRNA expression was maintained until 1 month after the injury. In situ
      hybridization and immunofluorescent showed that both neurons and non-neuronal
      cells express Unc5a and b mRNAs in the adult spinal cord, and the significant
      long lasting down-regulation of Unc5a mRNA expression was also noticed following
      the spinal cord injury. This result suggests netrin/UNC5 involvement in the
      injury response of the adult spinal cord of the rats.

PMID- 17452078
TI  - Rhythmic leg cycling modulates forearm muscle H-reflex amplitude and
      corticospinal tract excitability.
AB  - Rhythmic arm cycling leads to suppression of H-reflexes in both leg and arm
      muscles, and a reduction in the excitability of corticospinal projections to the
      forearm flexors. It is unknown, however, whether leg cycling modulates
      excitability in neural projections to the arms. Here we studied the extent to
      which rhythmic movement of the legs alters reflex (Experiment 1) and
      corticospinal (Experiment 2) transmission to arm muscles. In experiment 1, flexor
      carpi radialis (FCR) H-reflex recruitment curves were recorded with the legs
      static, and during rhythmic leg movement, while the FCR was both contracted and
      relaxed. The results indicate that rhythmic leg movement suppresses reflex
      transmission, both when FCR is at rest and during tonic contraction, but that the
      effect is not phase-dependent. In experiment 2, we used transcranial magnetic
      stimulation (TMS) to elicit motor-evoked potentials in the contracted and relaxed
      FCR during static leg, and leg cycling conditions. Sub-threshold TMS was also
      used to condition H-reflexes in order to provide specific information about
      cortical excitability during leg cycling. Both resting and tonically contracting
      arm muscles showed a greater corticospinal excitability during leg cycling than
      during the static leg condition. The magnitude of TMS facilitation of H-reflexes
      was similar during leg cycling and rest, suggesting a considerable sub-cortical
      component to the increased corticospinal excitability. The results suggest a
      differential regulation of afferent and descending projections to the arms during
      leg cycling, and are consistent with the idea that there is a loose, but
      significant, neural coupling between the arms and legs during rhythmic movement.

PMID- 17452079
TI  - gamma-Aminobutyric acid in the lateral septal area is involved in mediation of
      the inhibition of hypothalamic angiotensin II-sensitive neurons induced by blood
      pressure increases in rats.
AB  - Previously, we have demonstrated that intravenous phenylephrine-induced increases
      in blood pressure inhibit angiotensin II-sensitive neurons via gamma-aminobutyric
      acid (GABA) inputs in the anterior hypothalamic area (AHA). The lateral septal
      area (LSV) is also demonstrated to be involved in mediation of the baroreceptor
      reflex. To investigate central mechanisms involved in mediating the baroreceptor
      reflex, we examined whether GABA in the LSV is involved in mediation of the
      phenylephrine-induced inhibition of AHA angiotensin II-sensitive neurons.
      Microinjection of GABA into the LSV inhibited angiotensin II-sensitive neurons in
      the AHA of rats. The LSV GABA-induced inhibition of AHA neurons was abolished by
      pressure application of bicuculline onto the same AHA neurons. Intravenous
      injection of phenylephrine also inhibited AHA angiotensin II-sensitive neurons
      and the phenylephrine-induced inhibition of AHA neurons was abolished by
      microinjection of the GABAA receptor antagonist bicuculline into the LSV. In
      contrast, the LSV microinjection of bicuculline did not affect the inhibition of
      firing of AHA neurons induced by GABA pressure-applied in the AHA. These findings
      suggest that intravenous phenylephrine inhibits AHA angiotensin II-sensitive
      neurons via release of GABA in the LSV.

PMID- 17452077
TI  - Cloning and bioinformatics of amphibian mu, delta, kappa, and nociceptin opioid
      receptors expressed in brain tissue: evidence for opioid receptor divergence in
      mammals.
AB  - Opioid agonists produce analgesia in humans and other mammals by binding to three
      distinct types of G protein-coupled receptors; mu (MOR), delta (DOR), and kappa
      (KOR) opioid receptors. A fourth member of the opioid receptor family is the
      nociceptin or orphanin FQ receptor (ORL), however the role of the ORL receptor in
      analgesia is less clear. In the Northern grass frog, Rana pipiens, systemic and
      central administration of morphine and selective MOR, DOR, and KOR agonists
      produced dose-dependent antinociceptive effects blocked by the general opioid
      antagonist, naltrexone. The present study reports on the sequence, expression,
      and bioinformatics of four opioid receptor cDNAs cloned from Rana pipiens; rpMOR,
      rpDOR, rpKOR, and rpORL. These were the first opioid receptors cloned from a
      species of Class Amphibia, are selectively expressed in brain tissue, and show 70
      84% identity to their homologous mammalian opioid receptors. Comparisons within
      species showed that MOR, DOR, and KOR proteins are significantly less divergent
      in earlier-evolved vertebrates compared to humans and other mammals. Among the
      four types of opioid receptors, MOR proteins show the least sequence variation
      among the six vertebrate species. Additionally, phylogenetic analysis supports
      the hypothesis that the family of opioid receptor proteins are coded by four
      genes that arose from two gene duplications of a single ancestral opioid receptor
      gene.

PMID- 17452080
TI  - Gender differences in pain and depressive tendency among Chinese elders with knee
      osteoarthritis.
AB  - The purpose of this study was to explore gender differences in pain experiences,
      pain control beliefs, pain coping strategies, and depressive tendency among
      Chinese elderly with knee osteoarthritis (OA). Participants (N=199) were drawn
      from a previous convenience sample of outpatients with OA in Taiwan. Results
      indicated female elders tended to report higher scores on least pain, current
      pain and overall pain intensity than male elders (all p<0.01). Female elders also
      reported significantly greater pain disturbance than males across each item and
      for the overall score, except for walking. Males and females did not differ
      significantly in scores for pain control beliefs or for either pharmacological or
      non-pharmacological coping strategies. In addition, female elders tended to have
      greater depressive tendency than males. Results of regression analyses suggest
      that depressive tendency was a mediator of gender in predicting overall pain
      intensity and pain disturbance. In summary, this sample of elders showed gender
      differences in depressive tendency and some pain experiences but not in pain
      control beliefs and coping strategies. These results suggest that health care
      providers should be cautious about using gender differences to explain pain
      experiences among Chinese elders. In addition, health care providers may decrease
      these female patients' pain intensity and pain disturbance by treating depressive
      symptoms.

PMID- 17452081
TI  - Genetic variability of Trypanosoma evansi isolates detected by inter-simple
      sequence repeat anchored-PCR and microsatellite.
AB  - Studies on genetic variability in Trypanosoma evansi have been limited by a lack
      of high-resolution techniques. In this study, we have investigated the use of
      inter-simple sequence repeats (ISSR) and microsatellites in revealing
      polymorphism among T. evansi isolates. Twelve ISSR primers and five
      microsatellite loci were used to generate polymorphic bands and alleles,
      respectively, to investigate the genetic variability among T. evansi isolates
      from Africa and Asia. Seven of the twelve ISSR primers showed variability between
      isolates with a total of 71 fragments of which 49(69%) were polymorphic.
      Microsatellite analysis revealed a total of 60 alleles. On average the ISSR
      markers revealed a higher genetic diversity (23%) than microsatellites (21.1%).
      The two techniques showed a strong agreement of r=0.95 for Dice and r=0.91 for
      Jaccard indices in estimating the genetic distances between isolates. The
      distance UPGMA tree revealed two major clusters of T. evansi which correlate with
      the minicircle classification of subtype A and B. The cophenetic correlation
      coefficient between Dice and Jaccard based matrices were r=0.79 for
      microsatellites and r=0.73 for ISSR indicating a strong agreement between
      dendrograms. The results suggest that both ISSR and microsatellites markers are
      useful in detecting genetic variability within T. evansi.

PMID- 17452082
TI  - Freshly generated epithelium may be a donor site for the coverage of deep skin
      defects in the combined skin wounds.

PMID- 17452083
TI  - Food reformulations for improved health: A potential risk for microbial food
      safety?
AB  - While much information is available concerning the health promoting benefits
      associated with dietary reformulations (e.g. replacing sugar with aspartame and
      salt (NaCl) with KCl), to reduce the incidence of obesity and heart disease,
      potential food safety risks arising from such reformulations have received
      considerably less attention. Reformulation inevitably changes the intrinsic
      physico-chemical properties of the food, which may in turn support the growth of
      food-borne pathogens and ultimately their ability to cause disease. Thus, a
      better understanding of the microbiological food safety issues associated with
      product reformulation for increased health are required.

PMID- 17452084
TI  - 'Bioengineered Bugs' - a patho-biotechnology approach to probiotic research and
      applications.
AB  - Given the increasing commercial and clinical relevance of probiotic cultures,
      improving their stress tolerance profile and ability to overcome the
      physiochemical defences of the host is an important biological goal. Pathogenic
      bacteria have evolved sophisticated strategies to overcome host defences,
      interact with the immune system and modulate essential host systems. The 'Patho
      biotechnology' concept promotes the exploitation of these valuable traits for the
      design of more technologically robust and effective probiotic cultures with
      potentially improved biotechnological and clinical applications, as well as the
      development of novel vaccine and drug delivery platforms.

PMID- 17452085
TI  - An in vitro assessment of bioadhesive zinc/carbomer complexes for antimicrobial
      therapy within the oral cavity.
AB  - The effectiveness of antimicrobial agents in the oral cavity is limited by their
      retention at the site of action. In this work the antimicrobial cation zinc was
      complexed with the bioadhesive agent Carbopol 971P, in order to allow an extended
      antimicrobial effect. Zinc ions were shown to form stable complexes with the
      polymer, and were not released into distilled water. However, in the presence of
      other cations, it was possible to displace zinc over an extended period. A low pH
      was seen to enhance zinc release. The complexes were found to have similar
      bioadhesive properties to the polymer alone when tested using a buccal cell
      adsorption model and texture probe analysis. It was concluded that this complex
      shows promise as a means of allowing the extended delivery of zinc ions locally
      within the oral cavity.

PMID- 17452086
TI  - Cationic supported lipid bilayers for antigen presentation.
AB  - Polystyrene sulfate (PSS) particles (301 nm mean diameter) were covered with
      single cationic dioctadecyldimethylammonium bromide (DDA) bilayers and used for
      antigen adsorption and presentation. The antigen was a mixture of purified 18/14
      Taenia crassiceps proteins (18/14-Tcra). Firstly, the DDA/PSS assembly was
      characterized at 1mM NaCl and 5 x 10(9) PSS particles/mL over a range of DDA
      concentrations (0.001-1mM) by means of dynamic light scattering for particle
      sizing and zeta-potential analysis. 0.01 mM DDA is enough to produce homodisperse
      and cationic bilayer-covered particles. Secondly, under these experimental
      conditions, 18/14-Tcra adsorption isotherms onto biomimetic particles or
      aluminium hydroxide (Al(OH)3) yield limiting adsorption of 0.36 and 1.32 mg
      protein/mg biomimetic particles or Al(OH)3, respectively. Finally, in mice,
      superior humoral and cellular immunoresponse from serum IgG and footpad swelling
      was obtained for antigen/biomimetic particles in comparison to conventional
      Al(OH)3. Cationic bilayer-covered particles are a novel, highly organized and,
      possibly, general immunoadjuvant for antigen presentation and subunit vaccine
      design.

PMID- 17452087
TI  - Biochemical pathways generating post-mortem volatile compounds co-detected during
      forensic ethanol analyses.
AB  - In this contribution are presented the fermentations of the main substrates
      present in a decaying corpse, namely carbohydrates, amino acids, glycerol and
      fatty acids, generating the post-mortem volatile compounds that could be detected
      along with ethanol during the forensic ethanol analysis. The available literature
      (preferably reviews) on microbial metabolic pathways (enzymes, substrates,
      conditions) that are implicated in the formation of these volatiles has been
      reviewed. The microbial formation of the following volatiles is supported by the
      presented biochemical data: ethanol, acetaldehyde, acetone, 2-propanol, 1
      propanol, 1-butanol, isobutanol, isoamyl alcohol, d-amyl alcohol, acetate,
      propionate, butyrate, isobutyrate and ethyl esters (mainly ethyl acetate). The
      extracted information was correlated with the existing forensic literature on the
      post-mortem detected volatiles. The significance of the microbial produced
      volatiles on the selection of an appropriate internal standard for the ethanol
      analysis has been considered. Finally, the possible contribution of the presence
      of volatiles in the interpretation of ethanol analysis results in post-mortem
      cases is discussed.

PMID- 17452088
TI  - Migrating and herniating hydatid cysts.
AB  - OBJECTIVE: To present the prevalence and imaging findings of patients with
      hydatid disease (HD) showing features of migration or herniation of the hydatid
      cysts (HCs) and underline the clinical significance of this condition. MATERIALS
      AND METHODS: Between May 2003 and June 2006, 212 patients with HD were diagnosed
      by abdomen and/or thorax CT, searched for migrating or herniating HC. Imaging
      findings of 7 patients (5 women, 2 men with an age range of 19-63 years; mean+/
      S.D., 44+/-19 years) with HD showing transdiaphragmatic migration (6 subjects) or
      femoral herniation (1 subject) were evaluated. Diagnosis of all the patients were
      established by pathologic examination and migration or herniation was confirmed
      by surgery in all patients. RESULTS: Liver HD were identified in 169 (79.7%) of
      212 patients with HD. Transdiaphragmatic migration of HCs were identified in 6
      (3.5%) of the 169 patients with liver HD. In one patient, femoral herniation of
      the retroperitoneal HC into the proximal anterior thigh was identified. All of
      these seven patients exhibiting migration or herniation of HCs had active HCs
      including 'daughter cysts'. Two patients had previous surgery because of liver HD
      and any supradiaphragmatic lesion was not noted before operation. Findings of
      migration or herniation were confirmed by surgery. CONCLUSION: Active HCs may
      show migration or herniation due to pressure difference between the anatomic
      cavities, and in some of the patients, by contribution of gravity. Previous
      surgery may be a complementary factor for migration as seen in two of our
      patients. The possibility of migration or herniation in patients with HD should
      be considered before surgery.

PMID- 17452089
TI  - Efficiency of fluorescence in situ hybridization for bacterial cell
      identification in temporary river sediments with contrasting water content.
AB  - We studied the efficiency of two hybridization techniques for the analysis of
      benthic bacterial community composition under varying sediment water content.
      Microcosms were set up with sediments from four European temporary rivers. Wet
      sediments were dried, and dry sediments were artificially rewetted. The
      percentage of bacterial cells detected by fluorescence in situ hybridization with
      fluorescently monolabeled probes (FISH) significantly increased from dry to wet
      sediments, showing a positive correlation with the community activity measured
      via incorporation of (3)H leucine. FISH and signal amplification by catalyzed
      reporter deposition (CARD-FISH) could significantly better detect cells with low
      activity in dried sediments. Through the application of an optimized cell
      permeabilization protocol, the percentage of hybridized cells by CARD-FISH showed
      comparable values in dry and wet conditions. This approach was unrelated to (3)H
      leucine incorporation rates. Moreover, the optimized protocol allowed a
      significantly better visualization of Gram-positive Actinobacteria in the studied
      samples. CARD-FISH is, therefore, proposed as an effective technique to compare
      bacterial communities residing in sediments with contrasting water content,
      irrespective of differences in the activity state of target cells. Considering
      the increasing frequencies of flood and drought cycles in European temporary
      rivers, our approach may help to better understand the dynamics of microbial
      communities in such systems.

PMID- 17452090
TI  - Reliable Change Index scores for persons over the age of 65 tested on alternate
      forms of the Rey AVLT.
AB  - An issue that often confronts the clinician referred an elderly person for
      neuropsychological assessment is how to interpret the significance of changes in
      test scores over time. In this report, data useful for estimating the statistical
      significance of changes on the Rey Auditory Verbal Learning Test (AVLT) are
      presented. The sample tested comprised 253 healthy persons aged 65 and over
      taking part in a randomized double-blind trial of the effect on cognitive
      performance of lowering homocysteine using dietary supplements. Results were
      based on the full sample because of the absence of any treatment effects. Test
      retest data with a 1-year interval were used to estimate reliability coefficients
      and to calculate reliable change indices. The magnitude of a change necessary for
      a deterioration or improvement in scores at the two-tailed 90% confidence
      interval is given for the full sample, and persons above and below the age of 75.

PMID- 17452091
TI  - Sequencing and analysis of the Escherichia coli serogroup O117, O126, and O146 O
      antigen gene clusters and development of PCR assays targeting serogroup O117-,
      O126-, and O146-specific DNA sequences.
AB  - The O-antigen gene clusters of Escherichia coli serogroups O117, O126, and O146
      were sequenced, and 11, 10, and 11 open reading frames (ORFs) were identified,
      respectively. Genes required for O-antigen sugar biosynthesis, sugar transfer,
      and sugar processing were identified. Multiplex polymerase chain reaction (PCR)
      assays were developed targeting the wzx and wzy genes present in the O-antigen
      gene cluster of these serogroups. The assays were highly serogroup specific when
      tested against strains belonging to serogroups that were isolated from food,
      humans, animals, and environmental sources, as well as against representative
      strains belonging to ca. 165 different E. coli O serogroups and a number of non
      E. coli bacteria. Thus, the results demonstrate that the wzx and wzy gene
      sequences were specific to E. coli O117, O126, and O146 and can be used as
      diagnostic markers for rapid identification and detection of these serogroups.

PMID- 17452092
TI  - A new neural network for solving nonlinear projection equations.
AB  - This paper proposes a new recurrent neural network for solving nonlinear
      projection equations. The proposed neural network has a one-layer structure and
      is suitable for parallel implementation. The proposed neural network is
      guaranteed to be globally convergent to an exact solution under mild conditions
      of the underlying nonlinear mapping. Compared with existing neural networks for
      nonlinear optimization, the asymptotical stability and exponential stability of
      the the proposed network are obtained without the smooth condition of the
      nonlinear mapping. The proposed neural network can be used to find the
      equilibrium point of both the projection neural network and Hopfield-type neural
      network. Therefore, the proposed neural network is a good solver for a wider
      class of optimization and related problems. Illustrative examples further show
      that the proposed neural network can obtain a more accurate solution with a
      faster convergence rate than existing relevant methods.

PMID- 17452093
TI  - Stable carbapenem susceptibility rates among multidrug-resistant Acinetobacter
      spp. strains in a setting of high prevalence of carbapenem-resistant Pseudomonas
      aeruginosa.

PMID- 17452094
TI  - Conditional knock-out reveals that zygotic vezatin-null mouse embryos die at
      implantation.
AB  - Vezatin, a protein associated to adherens junctions in epithelial cells, is
      already expressed in mouse oocytes and during pre-implantation development. Using
      a floxed strategy to generate a vezatin-null allele, we show that the lack of
      zygotic vezatin is embryonic lethal, indicating that vezatin is an essential
      gene. Homozygous null embryos are able to elicit a decidual response but as early
      as day 6.0 post-coitum mutant implantation sites are devoid of embryonic
      structures. Mutant blastocysts are morphologically normal, but only half of them
      are able to hatch upon in vitro culture and the blastocyst outgrowths formed
      after 3.5 days in culture exhibit severe abnormalities, in particular disrupted
      intercellular adhesion and clear signs of cellular degeneration. Notably, the
      junctional proteins E-cadherin and beta-catenin are delocalized and not observed
      at the plasma membrane anymore. These in vitro observations reinforce the idea
      that homozygous vezatin-null mutants die at the time of implantation because of a
      defect in intercellular adhesion. Together these results indicate that the
      absence of zygotic vezatin is deleterious for the implantation process, most
      likely because cadherin-dependent intercellular adhesion is impaired in late
      blastocysts when the maternal vezatin is lost.

PMID- 17452095
TI  - Workshop outcomes report: initiatives to establish a European Network of
      pharmacogenetics/genomics and progress.

PMID- 17452096
TI  - Investigation of an artificial intelligence technology--Model trees. Novel
      applications for an immediate release tablet formulation database.
AB  - This study has investigated an artificial intelligence technology - model trees -
      as a modelling tool applied to an immediate release tablet formulation database.
      The modelling performance was compared with artificial neural networks that have
      been well established and widely applied in the pharmaceutical product
      formulation fields. The predictability of generated models was validated on
      unseen data and judged by correlation coefficient R(2). Output from the model
      tree analyses produced multivariate linear equations which predicted tablet
      tensile strength, disintegration time, and drug dissolution profiles of similar
      quality to neural network models. However, additional and valuable knowledge
      hidden in the formulation database was extracted from these equations. It is
      concluded that, as a transparent technology, model trees are useful tools to
      formulators.

PMID- 17452097
TI  - Solution formulation and lyophilisation of a recombinant fibronectin fragment.
AB  - The 9th-10th type III fibronectin domain pair shows promise in tissue engineering
      and tumour vasculature targeting. Calorimetry and structure-function analysis
      were used to investigate the effects of solution formulation and lyophilisation
      of a mutant ((9-10)FNIII-P). A single endothermic transition for (9-10)FNIII-P in
      solution was observed at pH<8, irrespective of addition of sucrose or PEG. The
      temperature at the maximum heat capacity (T(m)) and enthalpy (deltaH) of the
      transition increased for increasing sucrose concentrations but decreased for
      increasing PEG concentrations. The transition was fitted to a single two-state
      unfolding mechanism (in contrast to unfolding in guanidine. x HCl) and was
      partially reversible only at pH 4, with increasing concentrations of sucrose
      causing a marked fall in deltaH between scans. Circular dichroism spectra for the
      thermal unfolding of (9-10)FNIII-P at pH 4 showed loss of native beta-sheet
      structure and loss of aromatic contributions to the peak centred around 226 nm
      yielding an intermediate conformation, which in the presence of sucrose was more
      disordered. Despite a glass transition (T(g)') for (9-10)FNIII-P(aq) of -70
      degrees C, primary drying at -30 degrees C did not perturb its conformation upon
      reconstitution or its biological activity following lyophilisation; the addition
      of sucrose or PEG had no influence on structure or activity. The main
      consideration in the formulation of (9-10)FNIII-P was therefore pH.

PMID- 17452098
TI  - Melatonin loaded ethanolic liposomes: physicochemical characterization and
      enhanced transdermal delivery.
AB  - The current investigation aims to evaluate the transdermal potential of novel
      ethanolic liposomes (ethosomes) bearing Melatonin (MT), an anti-jet lag agent
      associated with poor skin permeation and long lag time. MT loaded ethosomes were
      prepared and characterized for vesicular shape and surface morphology, vesicular
      size, entrapment efficiency, stability, in vitro skin permeation and in vivo skin
      tolerability. Transmission Electron Microscopy (TEM), Scanning Electron
      Microscopy (SEM), and Dynamic Light Scattering (DLS) defined ethosomes as
      spherical, unilamellar structures having low polydispersity (0.032+/-0.011) and
      nanometric size range (122+/-3.5 nm). % Entrapment efficiency of MT in ethosomal
      carrier was found to be 70.71+/-1.4. Stability profile of prepared system
      assessed for 120 days revealed very low aggregation and growth in vesicular size
      (7.6+/-1.2%). MT loaded ethosomal carriers also provided an enhanced transdermal
      flux of 59.2+/-1.22 microg/cm2/h and decreased lag time of 0.9 h across human
      cadaver skin. Fourier Transform-Infrared (FT-IR) data generated to assess the
      fluidity of skin lipids after application of formulation revealed a greater
      mobility of skin lipids on application of ethosomes as compared to that of
      ethanol or plain liposomes. Skin permeation profile of the developed formulation
      further assessed by confocal laser scanning microscopy (CLSM) revealed an
      enhanced permeation of Rhodamine Red (RR) loaded formulations to the deeper
      layers of the skin (240 microm). Further, a better skin tolerability of ethosomal
      suspension on rabbit skin suggested that ethosomes may offer a suitable approach
      for transdermal delivery of melatonin.

PMID- 17452099
TI  - Development of potent oral nanoparticulate formulation of coenzyme Q10 for
      treatment of hypertension: can the simple nutritional supplements be used as
      first line therapeutic agents for prophylaxis/therapy?
AB  - Coenzyme Q10 (CoQ10) is an antioxidant with well-established pharmacological
      activities against several chronic diseases; however, it is marketed only as a
      nutritional supplement without any claims of its therapeutic activity and one of
      the reasons for this could be the poor oral bioavailability rendering
      difficulties in administering this molecule to achieve therapeutic
      concentrations. Therefore, the present investigation was aimed at improving the
      oral bioavailability of CoQ10 by delivering it as nanoparticulate formulation.
      Biodegradable nanoparticulate formulations based on poly(lactide-co-gylcolide)
      (PLGA) were prepared by emulsion technique using quaternary ammonium salt
      didodecyldimethylammonium bromide (DMAB) as a stabilizer. The effect of initial
      CoQ10 loading on entrapment efficiency and the particle size was studied using 5
      75% initial load resulting in good entrapment efficiency (61-83%) without any
      appreciable increase in the particle size for 5-30% loading (107-110 nm).
      However, 50% and 75% led to increase in particle size with no appreciable changes
      in entrapment efficiency. The intestinal uptake of CoQ10 as a suspension in
      carboxymethylcellulose (CMC), a commercial formulation and the developed
      nanoparticulate formulation was studied in male Sprague-Dawley (SD) rats and
      found to be 45%, 75% and 79%, respectively, suggesting that solubility and
      permeability related problems of CoQ10 were overcome by nanoparticulate
      formulation. Furthermore, the developed nanoparticulate formulation was evaluated
      for its therapeutic potential in renal hypertensive animals (Goldblatt 2K1C
      model), demonstrating improved efficacy at a 60% lowered dose as compared to
      CoQ10 suspension and superior efficacy than the commercial formulation at an
      equal dose. Together, these results indicate the potential of nanotechnology in
      improving the therapeutic value of molecules like CoQ10, facilitating its usage
      as first line therapeutic agent thus revolutionizing its role in current medical
      therapy.

PMID- 17452100
TI  - Recycling of nutrients from organic wastes and treatment options. RAMIRAN'04.

PMID- 17452101
TI  - Extraction of cadmium and tolerance of three annual cut flowers on Cd
      contaminated soils.
AB  - To evaluate the production potential and Cd removal by three flower crops, viz.:
      marigold (Tagetes erecta), chrysanthemum (Chrysanthemum indicum) and gladiolus
      (Gladiolus grandiflorus), an experiment was conducted on differentially
      contaminated soils (DTPA-Cd 0.6-68.4 mg kg(-1)). Biotoxicity of Cd lead to
      reductions in growth and flower yield of marigold at DTPA-Cd >or= 7.9 mg kg(-1)
      soil, while the productivity of chrysanthemum and gladiolus was sustained up to
      21.2 mg kg(-1). DTPA-Cd for 50% yield reduction (C(50)) was 85, 106 and 215 mg
      kg(-1) soil for marigold, chrysanthemum and gladiolus, respectively, that
      indicates a better Cd-tolerance in gladiolus. The uptake of Cd increased with
      contents in soils and the maximum accumulation occurred in leaves. Among the
      economic parts, gladiolus spikes accumulated the highest Cd (7.2) followed by
      flowers of marigold (6.5) and chrysanthemum (4.0 mg kg(-1)). But, because of
      higher biomass, the total Cd removal was the maximum with chrysanthemum (8.3)
      followed by gladiolus (6.0) and the minimum (2.6 mg m(-2)) with marigold.
      Gladiolus with highest tolerance and Cd-content in saleable part holds potential
      to clean up the moderately contaminated soils.

PMID- 17452102
TI  - (Arylpiperazinyl)cyclohexylsufonamides: discovery of alpha(1a/1d)-selective
      adrenergic receptor antagonists for the treatment of Benign Prostatic
      Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS).
AB  - Benign Prostatic Hyperplasia/Lower Urinary Tract Symptoms (BPH/LUTS) can be
      effectively treated by alpha(1)-adrenergic receptor antagonists. Unfortunately,
      all currently marketed alpha(1) blockers produced CV related side effects that
      are caused by the subtype non-selective nature of the drugs. To overcome this
      problem, it was postulated that a alpha(1a/1d) subtype selective antagonist would
      bring more benefit for the treatment of BPH/LUTS. In developing selective
      alpha(1a/1d) ligands, (arylpiperazinyl)cyclohexylsulfonamides were synthesized
      and their binding profiles against three cloned human alpha(1)-adrenergic
      receptor subtypes were evaluated. Many compounds show equal affinity for both
      alpha(1a) and alpha(1d) subtypes with good selectivity against the alpha(1b)
      subtype. They also overcome the problem of dopamine receptor affinity that
      previous analogues had exhibited.

PMID- 17452103
TI  - Oxidative aromatization of Hantzsch 1,4-dihydropyridines in the presence of mixed
      addenda vanadomolybdophosphate heteropolyacid, H6PMo9V3O40.
AB  - A variety of Hantzsch 1,4-dihydropyridines were oxidized to the corresponding
      pyridines in high yields in the presence of H(6)PMo(9)V(3)O(40), a Keggin type
      heteropolyacid, in refluxing acetic acid. The heteropolyacid was found to be
      reusable.

PMID- 17452104
TI  - Strength and corticosteroid responsiveness of mdx mice is unchanged by RAG2 gene
      knockout.
AB  - Corticosteroids improve muscle function in boys with Duchenne muscular dystrophy
      and mdx mice possibly via effects on T-cell and B-cells. We quantified T-cell/B
      cell functional effects and refined prednisolone's therapeutic mechanism in mdx
      mice. RAG2(-/-) mice, which produce no T-cells or B-cells, were crossed with mdx
      mice, which lack dystrophin protein. Strength testing (3-36 weeks) was performed
      on treated and control groups of male mdx RAG2(-/-)and mdx RAG2(+/-) mice.
      Longitudinal grip strength testing and hanging wire testing were assessed.
      Voluntary wheel running and creatine kinase level were measured. The absence of T
      cells/B-cells (RAG2(-/-) mutation) caused no physiologic improvement.
      Prednisolone improved performance in mdx mice, independent of RAG2 gene
      expression (+ or -/-). Prednisolone treatment increased the frequency of muscle
      calcification, while RAG2 genotype had no effect. There was no change in fiber
      type proportions due to RAG2 genotype or prednisolone treatment. Thus, T-cells
      and/or B-cells (and immunoglobulins), while demonstrable in mdx mouse muscle, are
      playing a negligible role in their mdx-related functional outcome. Prednisolone's
      therapeutic effect is through T-cell/B-cell independent mechanisms in mdx mice.

PMID- 17452105
TI  - Penetrating craniocerebral injuries from nail-gun use.
AB  - Three patients with penetrating craniocerebral nail-gun injuries are described.
      In the first patient the nail was impinging on the internal carotid artery (ICA)
      in the carotid canal. On removal of the nail, the patient developed a false
      aneurysm at the site. To our knowledge, this is the first reported case of nail
      gun injury affecting the ICA and also the first case of penetrating head injury
      affecting the ICA in the carotid canal. The second patient had seven intracranial
      nails in the frontal area. Three nails penetrated the left orbit, one of which
      perforated the globe. One nail damaged the optic nerve resulting in optic
      neuropathy. In the third patient the nail extended through the squamous temporal
      bone into the temporal lobe. All three were managed successfully via closed
      gentle traction without craniotomy and/or endovascular intervention. The
      literature is reviewed and management options for penetrating head injuries are
      discussed.

PMID- 17452107
TI  - Synthesis and pharmacological investigation of novel 4-benzyl-1-substituted-4H
      [1,2,4]triazolo[4,3-a]quinazolin-5-ones as new class of H1-antihistaminic agents.
AB  - A series of novel 1-substituted-4-benzyl-4H-[1,2,4]triazolo[4,3-a]quinazolin-5
      ones were synthesized by the cyclization of 2-hydrazino-3-benzyl-3H-quinazolin-4
      one with various one-carbon donors. The starting material 2-hydrazino-3-benzyl-3H
      quinazolin-4-one was synthesized from benzylamine by a new innovative route. When
      tested for their in vivo H1 -antihistaminic activity on guinea pigs, all the test
      compounds protected the animals from histamine induced bronchospasm
      significantly. The compound 1-methyl-4-benzyl-4H-[1,2,4]triazolo[4,3-a]quinazolin
      5-one (II) emerged as the most active compound of the series and it is more
      potent (percent protection 76%) when compared to the reference standard
      chlorpheniramine maleate (percent protection 71%). Compound II showed negligible
      sedation (7%) when compared to chlorpheniramine maleate (30%). Hence it could
      serve as prototype molecule for further development as a new class of H1 
      antihistamines.

PMID- 17452106
TI  - When biochemistry meets structural biology: the cautionary tale of EmrE.
AB  - When biochemistry meets structural biology a more complete understanding of the
      mechanism of biological macromolecules is usually achieved. Several high
      resolution structures of ion-coupled transporters have enriched the understanding
      of mechanisms of substrate recognition, translocation and coupling of substrate
      fluxes. However, two X-ray structures of EmrE, the smallest ion-coupled multi
      drug transporter, raised questions over the veracity of the structural model and
      represented a cautionary tale about the difficulty of determining the 3D
      structures of membrane proteins and the dangers of ignoring biochemical results.
      The 3D structures of EmrE have since been retracted because of faulty software,
      but the suggestion that the protomers in the dimer are in an antiparallel
      topological orientation sparked controversy that is still ongoing.

PMID- 17452108
TI  - Synthesis and antifungal activities of 5-(3,4,5-trimethoxyphenyl)-2-sulfonyl
      1,3,4-thiadiazole and 5-(3,4,5-trimethoxyphenyl)-2-sulfonyl-1,3,4-oxadiazole
      derivatives.
AB  - Starting from the key intermediate 5-(3,4,5-trimethoxyphenyl)-1,3,4-thiadiazole-2
      thiol (4) or the oxadiazole analogue (5), the title compounds 9 and 10 are
      synthesized by a two-step process. Thioetherification reaction of 4 or 5 with an
      organic halide catalyzed by indium or indium tribromide first affords appropriate
      sulfide 7 or 8, which is then converted into title compounds 9 or 10 by hydrogen
      peroxide oxidation catalyzed by ammonium molybdate in ionic liquid [bmim]PF6. The
      structures are unequivocally confirmed by spectroscopic (IR, 1H and 13C NMR) data
      and elemental analyses. The structures of 8d and 10q are further established by X
      ray crystallographic diffraction analysis. The compounds have been shown to be
      fungicidally active. Title compounds 10i and 10j can inhibit mycelia growth by
      approximately 50% (EC50) at 2.9-93.3 microg/mL in vitro against 10 kinds of
      fungi.

PMID- 17452109
TI  - Activity of a cationic carotenoid derivative in a mouse model of protoporphyria.
AB  - Prior work using cell culture has shown that certain synthetic carotenoid
      derivatives are more effective than natural carotenoids in preventing
      photosensitized cell killing. These carotenoid derivatives are either cationic or
      are weak bases. We have now found that of one of these derivatives, the Girard's
      reagent T derivative of beta-apo-8'-carotenal (GRT-carotenal) decreases acute
      photosensitivity in a mouse model of protoporphyria. When GRT-carotenal was added
      to the diet of SKH1 mice, both GRT-carotenal and its metabolites accumulated in
      the skin of the mice. Protoporphyria was induced in SKH1 mice by adding collidine
      to their diet. When the porphyric mice were exposed to 400 nm light (2.6+/-0.1 mW
      cm(-2)) for a period of 2h, the skin on the backs of these animals increased in
      thickness. Increased vascularity also developed in the skin of the mouse ears.
      Animals, that were fed a diet containing both collidine and GRT-carotenal and
      then exposed to light, had significantly smaller increases in skin thickness and
      less prominent increases in the vascular pattern on their ears.

PMID- 17452110
TI  - Microbiological contamination in stem cell cultures.
AB  - Cell therapy and regenerative medicine are potentially two of the most exciting
      aspects of the novel therapeutic methods currently under development. However,
      these treatments present a number of important biosafety issues, like the
      possible transmission of microorganisms to the recipients. The most common
      potential form of contamination in these cell products is by bacteria (including
      Mycoplasma), yeast and fungi. In our study, 32 stem cell lines and feeder cell
      lines were analysed. There were 19 contaminated cell passages (12%). The main
      contaminants were gram positive cocci and Mycoplasma species, followed by gram
      negative rods and gram positive rods. The Mycoplasma contamination rate was 4%.
      Stem cell banks and other research centres aim to screen all processed stem cell
      lines for these microorganisms, and to assure that no contaminants are introduced
      in the banking procedures. It is a standard part of current good practice in stem
      cell banks to carry out routine microbiological controls of the stem cell lines
      and to work in a controlled environment to reduce the probability of
      contamination in the final product.

PMID- 17452111
TI  - Antigen expression of cord blood derived stem cells under osteogenic stimulation
      in vitro.
AB  - Tissue engineering strategies have become a promising option for treating
      musculoskeletal defects in future. Cord blood includes mesenchymal stem cells
      which are able to differentiate into several cell lines under lineage specific
      stimulation including osteoblasts, chondroblasts and adipoblasts. In this study
      the antigen pattern of cord blood stem cells cultivated onto a porous porcine
      collagen I/III scaffold is investigated. The cultures were stimulated with
      osteogenic mixture (dexamethasone, ascorbic acid, glycerolphosphatate [DAG]) over
      21days in vitro. The following antigens and markers served for immuncytochemical
      evaluation: bone sialoprotein, osteocalcin, osteonectin, osteopontin, cartilage
      proteoglycan, chondrogenic oligomeric matrix protein, collagen I/II/III/X, CD13,
      CD 31, CD34, CD44, CD45, CD105, fibroblast growth factor receptor 2, vascular
      endothelial growth factor, vimentin and von-Kossa and HE stainings. We showed
      that a collagen I/III scaffold is an appropriate cellular carrier for cord blood
      progenitor cells and allows for an osteoblastic differentiation. Moreover there
      were differences in antigen pattern, dependent on the location of the adherent
      cells. CD105 and VEGF were only expressed at the bottom of the biomaterial.
      Future investigations should show the role of cytomechanical forces in the
      differentiation of cord blood derived progenitor cells and also if a cell-loaded
      collagen I/III scaffold is appropriate to stimulate bone regeneration in vivo.

PMID- 17452112
TI  - Anti-oxidation and immune responses in mice upon exposure to manganese superoxide
      dismutase expressed in silkworm larvae, Bombyx mori L.
AB  - With manganese superoxide dismutase expressed in silkworm larvae, Bomby mori L,
      we investigate the effects of silkworm larvae powder containing SOD on the
      antioxidation and the immune system of mouse. The contents of MDA both in mice
      plasma or liver organ treated with silkworm larvae powder containing manganese
      superoxide dismutase were reduced compare to control. The superoxide dismutase
      (SOD) and glutathione peroxidase (GSH-Px) activities both in plasma or liver
      organ of the treated mice were significantly higher than that of both control and
      bromobenzene treated mice (group-BM), suggesting the silkworm larvae powder
      containing SOD play a positive role in anti-oxidation in mice. This experiment
      was also designed to investigate the effects of silkworm larvae powder containing
      SOD on the immune system of mouse, focused on hemolysin response,
      hemagglutination against SRBC and the activity of natural killer (NK) cells. All
      treated mice showed significant increase in hemolysin response to SRBC and
      demonstrated an activation of NK cell function by the SOD-contained silkworm
      larvae powder, which suggest a promotion in humoral immunity. The results
      suggested the SOD expressed in silkworm maybe have potential application in
      medicine.

PMID- 17452114
TI  - Knockdown of endothelial NOS by lentivirus-mediated short hairpin RNA in
      hemangioendothelioma cells increases proliferation and tumor formation.
AB  - Endothelial nitric oxide synthase (ecNOS) derived nitric oxide (NO) is a key
      contributor to the angiogenic process. By augmenting angiogenesis NO could
      potentially promote tumor progression. The object of this study was to determine
      how knockdown of ecNOS affects endothelial NO production and the angiogenic
      response in endothelial cells. EOMA cells derived from a spontaneously arising
      murine hemangioendothelioma were genetically manipulated to stably express siRNA
      targeting ecNOS. Knockdown of ecNOS in different stably transfected EOMA cell
      lines was demonstrated by quantitative RT-PCR, Western blot and ecNOS specific
      ELISA. An EOMA cell line with near complete knockdown of ecNOS exhibited
      dramatically altered morphology and changes in the expression of mRNAs encoding
      proteins involved in angiogenesis. This cell line exhibited a 4-fold increase in
      proliferation in vitro, altered tube formation in matrigel and formed tumors in
      mice more rapidly than the parental cells. In contrast, a cell line in which
      ecNOS protein levels were reduced only 5-fold did not show changes in
      proliferation rate, tube formation or tumor growth. These results suggest that
      ecNOS derived nitric oxide reduces the growth of hemangioendothelioma derived
      tumors, and underscore the importance of careful consideration of the tumor type
      when selecting modulation of nitric oxide signaling as a treatment strategy.

PMID- 17452113
TI  - RNA localization signals: deciphering the message with bioinformatics.
AB  - mRNA localization is an important posttranscriptional method of targeting
      proteins to their site of function. The sorting of transcripts to their correct
      intracellular destination is achieved by a number of mechanisms, including
      selective degradation or transport by molecular motors along the cytoskeleton. In
      all cases, this involves mRNA localization signals, or so called zip codes, being
      recognized by trans-acting cellular factors. In a few cases, primary sequence
      motifs for RNA localization can be identified, but in general, localization
      signals operate at the level of secondary (2D) and tertiary (3D) structure. This
      inevitably means that searching for localization signal motifs is a complex task
      requiring specialist knowledge of bioinformatics. Furthermore, the publications
      describing these searching methods tend to be aimed at the bioinformatics
      community. In this review, we have surveyed the major tools for folding,
      comparing, and searching potential mRNA localization signals in transcripts or
      across genomes. Our aim is to provide an overview for biologists, who lack
      specialist computer and bioinformatics training, of the major RNA bioinformatics
      tools that are available. The examples provided are focused on mRNA localization
      signals and RNA stem-loop structures, however, these tools can be applied to the
      study of any RNA signals.

PMID- 17452115
TI  - Down-regulation of matrix metalloproteinase-9 expression by nitric oxide in
      lipopolysaccharide-stimulated rat primary astrocytes.
AB  - Immunologically activated astrocytes over-express matrix metalloproteinase-9 (MMP
      9) and nitric oxide (NO). Because they have both beneficial and detrimental
      effects on the pathophyiological outcomes of several neurological diseases, their
      expression should be tightly regulated in the CNS. NO can modify the activity of
      other proteins either by directly modifying protein structure or regulating the
      expression of target proteins. In this study, we investigated the role of NO on
      the expression of MMPs in rat primary astrocytes. Rat primary astrocytes were
      stimulated with lipopolysaccharide (LPS), resulting in the over-expression of
      both MMP-9 and NO. Inhibition of NO production using nitric oxide synthase
      inhibitor, Nomega-nitro-l-arginine methyl ester (l-NAME), further increased MMP-9
      expression, suggesting NO inhibits MMP-9 expression. In line with this
      observation, exogenous addition of NO donor, sodium nitroprusside (SNP) or S
      nitroso-N-acetylpenicillamine (SNAP), inhibited MMP-9 expression in astrocytes.
      The inhibitory effect of NO was mediated by the down-regulation of mRNA and
      protein levels of MMP-9 but not by the direct modification of the enzymatic
      activity of MMP-9. The effect of NO on MMP-9 expression was mimicked by dibutyryl
      cGMP and inhibited by PKG inhibitor KT5823, suggesting NO regulates MMP-9
      expression via guanylate cyclase-PKG pathway. Finally, SNP or dibutyryl-cGMP
      inhibited the activation of ERK1/2 in LPS-stimulated astrocytes, which is an
      essential regulator of MMP-9 expression in astrocytes. The regulation of MMP-9
      expression by NO may confer additional levels of fine-tuning of the level of MMP
      9 during brain inflammatory conditions.

PMID- 17452116
TI  - An automated method for the measurement of methaemoglobin in avian blood.
AB  - An automated method has been developed for the measurement of methaemoglobin
      (metHb) in blood using a biochemistry analyser. The method was validated using
      blood collected from red-legged partridges exposed in vitro to increasing
      concentrations of nitrite in order to obtain different percentages of metHb.
      Results obtained using the original manual method and those using the new
      automated technique were compared and no significant differences were found.
      Intra-day and inter-day variabilities (8.8% and 2.6%, respectively) were
      acceptable for samples containing high levels (63-81%) of metHb. Methaemoglobin
      measured in blood samples stored in liquid nitrogen was stable for 10 days, but
      increased significantly by day 20 in nitrite-treated samples.

PMID- 17452117
TI  - Flexible therapeutic landscapes of labour and the place of pain relief.
AB  - Flexibility in the design and enactment of spaces of healthcare is important in
      how providers respond to variations in patient expectations and experience.
      Health geographers have contributed to a wide body of literature concerning the
      therapeutic qualities of landscapes and the material, social and symbolic
      orderings of place and their uniqueness for individuals. In this paper, we draw
      upon these findings and a 'culture of place' approach to consider the
      complexities of maternity care and issues of pain relief. Given that pain is
      widely held to be a subjective experience and one that, in an era of patient
      decision making, increasingly demands discretionary approaches to its relief, we
      consider how medical professionals help to construct flexibility in healthcare
      and how this affects therapeutic landscapes. Drawing on analysis of four focus
      groups involving parent educators, midwives, health visitors, anaesthetists and
      obstetricians in the NE of England, we explore the material and discursive
      construction of flexible therapeutic landscapes and pain relief. Our findings
      suggest that flexibility is constrained and fashioned in association with health
      care professional's sense of place as already constituted. We propose that
      providing maternity care professionals with an explicit awareness of how places
      are relationally constructed, may help in expanding the therapeutic qualities of
      particular settings, and support a (more) flexible approach.

PMID- 17452118
TI  - Changes in postural activity of the trunk muscles following spinal manipulative
      therapy.
AB  - Spinal manipulative therapy (SMT) is common in the management of low back pain
      (LBP) and has been associated with changes in muscle activity, but evidence is
      conflicting. This study investigated the effect of SMT on trunk muscle activity
      in postural tasks in people with and without LBP. In 20 subjects (10 with LBP and
      10 controls), EMG recordings were made with fine-wire electrodes inserted into
      transversus (TrA), obliquus internus (OI), and externus (OE) abdominis. Rectus
      abdominis (RA) and anterior deltoid EMG was recorded with surface electrodes.
      Standing subjects rapidly flexed an arm in response to a light, before and after
      a small amplitude end range rotational lumbar mobilization at L4-5. In controls,
      there was no change in trunk muscle EMG during the postural perturbation after
      SMT. In LBP subjects there was an increase in the postural response of OI and an
      overall increase in OE EMG. There was no change in TrA or RA EMG. These results
      indicate that SMT changes the functional activity of trunk muscles in people with
      LBP, but has no effect on control subjects. Importantly, SMT increased the
      activity of the oblique abdominal muscles with no change in the deep trunk muscle
      TrA, which is often the target of exercise interventions.

PMID- 17452119
TI  - Targeting tumor stroma and exploiting mature tumor vasculature to improve anti
      cancer drug delivery.
AB  - The identification of a critical role of tumour stroma in the regulation of
      tumour interstitial fluid pressure and the simultaneous discovery of the impact
      of anti-angiogenic drugs on tumour hemodynamics have provided new potential for
      improving tumour delivery of anti-cancer drugs. Here, we review the most recent
      studies investigating how tumour-associated fibroblasts and macrophages as well
      as the extracellular matrix itself may be targeted to facilitate delivery of both
      low-molecular weight drugs and macromolecules. In addition, we summarize the
      current understanding of the use of vasoactive compounds, radiotherapy and
      vascular-disrupting agents as potential adjuvants to maximize tumour delivery of
      anti-cancer drugs. The impact of these strategies on the diffusive and convective
      modes of drug transport is discussed in the light of Fick's and Starling's laws.
      Finally, we discuss how transcytosis through caveolae may also be exploited to
      optimize the selective delivery of conventional chemotherapy to the
      subendothelial tumour cell compartment.

PMID- 17452120
TI  - Cytogenetic effects of extremely low frequency magnetic field on Wistar rat bone
      marrow.
AB  - In this study, the genotoxic and cytotoxic potential of extremely low frequency
      magnetic fields (ELF-MF) was investigated in Wistar rat tibial bone marrow cells,
      using the chromosomal aberration (CA) and micronucleus (MN) test systems. In
      addition to these test systems, we also investigated the mitotic index (MI), and
      the ratio of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes
      (NCEs). Wistar rats were exposed to acute (1 day for 4h) and long-term (4h/day
      for 45 days) to a horizontal 50Hz, 1mT uniform magnetic field generated by a
      Helmholtz coil system. Mitomycin C (MMC, 2mg/kg BW) was used as positive control.
      Results obtained by chromosome analysis do not show any statistically significant
      differences between the negative control and both acute and long-term ELF-MF
      exposed samples. When comparing the group mean CA of long-term exposure with the
      negative control and acute exposure, the group mean of the long-term exposed
      group was higher, but this was not statistically significant. However, the mean
      micronucleus frequency of the longer-term exposed group was considerably higher
      than the negative control and acutely exposed groups. This difference was
      statistically significant (p<0.01). The results of the MI in bone marrow showed
      that the averages of both A-MF and L-MF groups significantly decreased when
      compared to those in the negative control (p<0.001 and p<0.01, respectively). No
      significant differences were found between the group mean MI of A-MF exposure
      with L-MF. We found that the average of PCEs/NCEs ratios of A-MF exposed group
      was significantly lower than the negative control and L-MF exposed groups
      (p<0.001 and p<0.01, respectively). In addition, the group mean of the PCEs/NCEs
      ratios of L-MF was significantly lower than negative control (p<0.01). We also
      found that the MMC treated group showed higher the number of CA and the frequency
      of MN formation when compared to those in all other each groups (p-values of all
      each groups <0.01) and also MMC treated group showed lower MI and the PCEs/NCEs
      ratios when compared to those in all other each groups (p-values of all groups
      <0.01). These observations indicate the in vivo suspectibility of mammals to the
      genotoxicity potential of ELF-MF.

PMID- 17452121
TI  - The determination of trace lead in Chinese medicinal herbs by flow injection
      analysis in polyethyleneglycol medium.
AB  - In this work, a new flow injection analysis (FIA) for the determination of Pb(2+)
      in Chinese medicinal herbs was developed. In the buffer solution of borax-NaOH
      (pH 10.5), Pb(2+) reacted with 2-[(5-bromo-2-pyridyl)-azo]-5-(diethyl
      amino)phenol (5-Br-PADAP) to form a complex. The experimental results showed that
      the sensitivity was enhanced in the presence of polyethyleneglycol-800 (PG-800).
      The main factors affecting the determination were investigated in detail. Under
      the optimum conditions, the linear range and detection limit is 0.0-0.3microg/mL
      and 1.5ng/mL (correlation coefficient r=0.9996), respectively. The linear
      regression equation is A=-0.005+0.60c (microg/mL). The sample throughout is 10h(
      1). Foreign substrates effects were also investigated. The proposed method has
      been successfully applied to the determination of lead in reference material,
      goldthread and lepidium seed.

PMID- 17452122
TI  - Informal notes to support the asynchronous collaborative activities.
AB  - BACKGROUND: Health care professionals' collaboration is highly important for the
      medical practice. Efficient exchange of information improves good cooperation,
      but remains complex, due to the diversity of the medical activities. Currently,
      the health record is mainly used to manage structured medical information. On the
      one hand, such structure supports treatment that requires the documented
      information. On the other hand, however, the structure also imposes constraints
      on narrative and conversational practices of health care professionals. They use
      other collaboration means through phone, mail, annotations and free texts for
      informal strategies of communication. We focussed on informal written documents.
      Two different studies provided us some materials: home care charts in the context
      of home care and annotations in the context of the hospital health records.
      PURPOSES: We wanted to design a model of the Communication Notes to computerize
      the written notes so as to improve the communication and the coordination of the
      practitioners. METHODS: We compared the results of the two studies about the
      various writing strategies used by the health care professionals to keep traces
      of their exchanges and of their acts. The first study deals with the information
      mentioned by the nurses in a chart during home care situations. We analysed the
      distribution of cooperation activities in action and in planning. The second
      study deals with the annotations which are written by all the practitioners to
      complete the documents of the health record in a paediatric ward. We analysed how
      annotations take part in their collaborations. RESULTS: We found some invariable
      items in these two situations and we proposed a model for these Communication
      Notes which can be used to describe and to index them according to different
      points of view. Some indications on the way such descriptions are used in current
      computerized systems are also reported. The originality of this model comes from
      the way it takes into account a collaborative perspective which is not often used
      in the electronic medical settings. CONCLUSIONS: With our model of Communication
      Notes, we now dispose of a promising setting for managing all the informal and
      unforeseeable information produced by the health care professionals during care.

PMID- 17452123
TI  - Origin of facilitation in repetitive, 1.5ms interval, paired pulse transcranial
      magnetic stimulation (rPPS) of the human motor cortex.
AB  - OBJECTIVE: Repetitive paired-pulse TMS (rPPS) given at an interstimulus interval
      (ISI) of 1.5 ms has been reported to induce a lasting motor evoked potential
      (MEP) facilitation. This after-effect was considered to be a cortical event
      because F-waves were not affected by the same rPPS. To confirm its cortical
      facilitation, we compared the after-effects of rPPS on MEPs to single pulse TMS
      over the motor cortex (motor cortical MEPs) with those to brainstem stimulation
      (brainstem MEPs). METHODS: Subjects were 10 healthy volunteers. Suprathreshold
      paired-pulse TMS at an ISI of 1.5 ms was applied to the motor cortex for 30 min
      at a rate of 0.2 Hz. After intervention, we measured motor cortical MEPs for 30
      min. We also studied brainstem MEPs in five subjects. RESULTS: Motor cortical
      MEPs were facilitated to about 190% of baseline (p<0.001) for 10 min post rPPS
      intervention and returned to the baseline at 10-15 min post intervention.
      Brainstem MEPs were not affected by the intervention. CONCLUSIONS: The
      facilitation of MEPs after rPPS at an interval of 1.5 ms occurs at the motor
      cortex. SIGNIFICANCE: rPPS at an interval of 1.5 ms is an effective method for
      increasing motor cortical excitability.

PMID- 17452124
TI  - Quantification of trunk rotations during turning and walking in Parkinson's
      disease.
AB  - OBJECTIVE: To develop a reliable, objective and sensitive measure of axial trunk
      rotations in PD, which can be applied in an ambulatory setting. METHODS: To
      quantify turning motion, two angular velocity transducers attached to the lower
      back measured angular velocity of the trunk in the yaw plane (i.e., around the
      longitudinal axis) and the roll plane (i.e., medio-lateral movements) in freely
      moving subjects who were instructed to walk and make various types of turning
      movements. RESULTS: Turn duration was longer in PD patients compared to controls.
      Peak yaw and peak roll angular velocities were lower in PD patients compared to
      controls during all turning tasks. CONCLUSIONS: This new approach to measure
      trunk sway during a simple turning task might serve as an instrument to
      objectively quantify turning while walking in PD. SIGNIFICANCE: It proves
      difficult to objectively assess turning performance based upon history taking or
      clinical examination alone. Objective and easy measurement of axial turning in PD
      might be used for clinical evaluation, but also in a domestic setting as outcome
      measure in intervention studies. Further research should focus on the clinical
      relevance of the new quantitative approach described in this paper, e.g., to
      detect freezing of gait episodes.

PMID- 17452125
TI  - The four horsemen of the oscilloscope: dynamic ultrasound, static ultrasound,
      electromyography and nerve conduction studies.

PMID- 17452126
TI  - Advances in sepsis research derived from animal models.
AB  - Inflammation is the basic process by which tissues of the body respond to
      infection. Activation of the immune system normally leads to removal of microbial
      pathogens, and after resolution of the inflammation immune homeostasis is
      restored. This controlled process, however, can be disturbed resulting in
      disease. Therefore, many studies using infection models have investigated the
      participating immune mechanisms aiming at possible therapeutic interventions.
      Defined model substances such as bacterial lipopolysaccharide (endotoxin) have
      been used to mimic bacterial infections and analyze their immune stimulating
      functions. A complex network of molecular mechanisms involved in the recognition
      and activation processes of bacterial infections and their regulation has
      developed from these studies. More complex infection models will now help to
      interpret earlier observations leading to the design of relevant new infection
      models.

PMID- 17452127
TI  - International strategies in children's environmental health.
AB  - In recent years the fact that children need to be protected against environmental
      stressors has been widely accepted by decision- and policy-makers. However, there
      is not yet a good or unified strategy to improve children's health by improving
      their environment. The Policy Interpretation Network on Children's Health and
      Environment (PINCHE) network suggested a range of recommendations to support the
      development of a strategy on children's environmental health on different levels
      of authority: international, national, regional, and local. There clearly are
      indicated bottlenecks in the thematic network approach. Three main challenges for
      success have been identified; first is data comparability. PINCHE identified the
      need for standardisation of environmental assessments, classification of
      childhood respiratory diseases and symptoms, and a format for defining diagnostic
      groups and presentation of data. Second, data accessibility must be addressed.
      Accessibility of the scientific data to the general public, including health
      professionals and policy makers, is important and requires translation that is
      often lacking. Third there is a requirement to harmonise definitions and methods
      to ensure that scientists and authorities speak the same language. Obstacles are
      the subsidiarity principle, fragmentation of available knowledge or lack of
      expertise and purpose at various levels, the lack of political commitment or
      input and economic issues.

PMID- 17452128
TI  - Cardiovascular manifestations in Fabry disease: a clinical and echocardiographic
      study.
AB  - This study reviews the clinical and echocardiographic findings in a cohort of
      Fabry patients (n=12) and compares echocardiographic findings to normal controls.
      Almost all patients had extracardiac manifestations. Five out of 12 patients had
      cardiovascular symptoms. Nine out of 12 patients had left ventricular hypertrophy
      (LVH) on the electrocardiogram (ECG) and one patient had short PR interval. Three
      patients had epicardial coronary disease. Four patients had 'rat-tail' appearance
      on left ventriculogram. Six patients who had myocardial biopsy showed extensive
      vacuolation of the myocytes on light microscopy and concentric, myelinoid
      lamellar cytoplasmic inclusion bodies on electron microscopy. On
      echocardiography, LV mass was significantly increased in the Fabry group compared
      to normal controls. Traditional parameters of diastolic function including peak E
      velocity, peak A velocity and deceleration time were no different to normal
      controls. The IVRT was significantly prolonged in the Fabry subjects. The PV
      atrial reversal duration exceeded that of mitral A wave duration in the Fabry
      group. The septal E' velocity with Doppler tissue imaging (DTI) was significantly
      lower in the Fabry group than the normal controls. Fabry disease should be
      considered in the differential diagnosis in patients with unexplained LVH and
      late onset hypertrophic cardiomyopathy. Extracardiac manifestations are common.

PMID- 17452129
TI  - Differential contributions of the hippocampus and rhinal cortices to verbal
      memory in epilepsy.
AB  - The present study explored the left mesial temporal lobe correlates of verbal
      memory in patients with temporal lobe epilepsy (TLE). An index of structural
      integrity, T2 relaxation time, was measured bilaterally in three mesial temporal
      regions of interest, and correlated with measures of verbal memory. The
      acquisition of verbal arbitrary relational material was most strongly associated
      with left perirhinal T2 signal. In contrast, verbal memory consolidation was
      related to T2 signal in the left hippocampus. Our findings suggest a key role for
      the left perirhinal region in the uptake of arbitrary linkages that underlie new
      learning. The hippocampus, on the other hand, is important for protecting newly
      learned information from the effects of interference. This double dissociation
      provides a neurocognitive account of the left mesial temporal memory syndrome.

PMID- 17452130
TI  - Ventilation-perfusion relationships in pulmonary arterial hypertension: effect of
      intravenous and inhaled prostacyclin treatment.
AB  - In seven patients with idiopathic or secondary pulmonary arterial hypertension
      (PAH), ventilation-perfusion (V (A)/Q ) relationships were measured during a
      right heart catheterization using the multiple inert-gas elimination technique
      before and during intravenous infusion with epoprostenol (EPO), and following 5
      months of 20 microg inhaled iloprost taken three times daily (ILO). Pre-treatment
      pulmonary vascular resistance (PVR) was 9.3+/-5.0 mmHg/l/min and the dispersion
      of perfusion and ventilation for V (A)/Q -ratios was increased. EPO reduced PVR
      by 20%, and increased cardiac output, shunt, and mixed venous oxygenation
      (SV(O2)). The arterial oxygen tension (Pa(O2)) remained unchanged. Basal central
      haemodynamics did not change after 5 months of ILO. Fifteen minutes after ILO,
      PVR decreased by 20%, and the shunt, SV(O2), and Pa(O2) remained unaltered.
      CONCLUSIONS: In secondary PAH with normal lung volumes, significant V (A)/Q
      mismatching occurred. The PVR was reduced to a similar degree during EPO and
      after ILO, but only EPO increased the shunt and SV(O2). EPO and ILO did not
      significantly affect the Pa(O2).

PMID- 17452131
TI  - A HPLC method for determination of nicousamide in dog plasma and its application
      to pharmacokinetic studies.
AB  - A sensitive and reproducible high performance liquid chromatography (HPLC)-UV
      method for determination of nicousamide, an inhibitor of rennin and transforming
      growth factor-beta1 (TGF-beta1) type II receptors, has been developed and
      validated. Following acetonitrile deproteiniation, samples were separated by
      isocratic reversed-phase HPLC on an Aichrom Bond-AQ C(18) column and quantified
      using UV detection at 320 nm. The mobile phase was acetonitrile/water (ratio
      62:38 containing 0.1% H(3)PO(4)), with a flow-rate of 1.0 ml/min. A linear curve
      over the concentration range 5-200 ng/ml (r(2)=0.9978) was obtained. The
      coefficients of the variation for the intra- and inter-day precisions ranged from
      1.4-10.7% and 1.8-7.1%, respectively. The percentage of relative recovery was
      91.56-105.45%. The method was used to determine the plasma concentration-time
      profiles for nicousamide after oral doses of 30, 100 and 300 mg/kg in dogs. A
      nonlinear pharmacokinetics was found in dogs at doses from 30 to 300 mg/kg.
      Following 30 mg/kg oral dose, the C(max) and AUC in females were lower than that
      in male. There is a potential for accumulation in dogs following multiple doses.

PMID- 17452132
TI  - "Infant mortality in Armenia 1992-2003": a comment.
AB  - The purpose of this comment is to counsel caution in some of the conclusions
      drawn in an otherwise fine article recently published in Economics and Human
      Biology on infant mortality in Armenia by Hakobyan, Mkrtchyan and Yepiskoposyan.
      These relate first, to the reliability of estimates and trends in infant
      mortality estimated from DHS data; second, to the interpretation of what the
      authors consider to be a 'low' infant mortality rate in former communist
      countries given their level of economic development; and third, to the role of
      the health care infrastructure in countries of the former Soviet Union in
      producing these 'low' infant mortality levels. This comment argues that trends in
      infant mortality in Armenia and other CIS countries, although probably declining,
      are perhaps less certain than the authors allow, that existing evidence does not
      suggest that they are uniformly low by global standards, or that the health care
      systems in CIS countries are uniformly effective in reducing infant deaths.

PMID- 17452133
TI  - Evolving concepts in the management of the bone gap in the upper limb. Long and
      small defects.
AB  - Vascularised bone graft is a well accepted technique when dealing with long
      defects. Its role in refractory nonunion, in small defects and in the growing
      patient is rarely discussed. In this paper the authors review the different
      alternatives to deal with bone defects in the upper extremity. The indications of
      vascularised corticoperiosteal graft for solving small defects harbouring
      refractory nonunion, and the use of vascularised bone phalanx and metatarsal for
      complex - but small - defects in the fingers is presented. The ability of the
      bone to grow and remodel when a living epiphysis is included, and to maintain the
      cartilage viability when a composite osteochondral graft is transferred are also
      discussed.

PMID- 17452134
TI  - AMPD1 gene polymorphism and survival in patients with stable congestive heart
      failure.

PMID- 17452135
TI  - The impact of the AMPD1 gene polymorphism on exercise capacity, other prognostic
      parameters, and survival in patients with stable congestive heart failure. A
      study on 686 consecutive patients.

PMID- 17452136
TI  - High-quality randomized trial of perioperative beta-blockade.

PMID- 17452138
TI  - Allogeneic blood transfusions and infections after cardiac surgery.

PMID- 17452140
TI  - Letter of comment on "Intracoronary nitroprusside for the prevention of the no
      reflow phenomenon after primary percutaneous coronary intervention in acute
      myocardial infarction. A randomized, double-blind, placebo-controlled clinical
      trial" (Am Heart J 2006;152:887.e9-14).

PMID- 17452142
TI  - Debate on DEBATE.

PMID- 17452144
TI  - Acute myocardial infarction and drug-eluting stents: a green light for their use
      or time for measured restraint?

PMID- 17452145
TI  - Prediction of first coronary events with the Framingham score: a systematic
      review.
AB  - BACKGROUND: Uncertainty exists about the performance of the Framingham risk score
      when applied in different populations. OBJECTIVE: We assessed calibration of the
      Framingham risk score (ie, relationship between predicted and observed coronary
      event rates) in US and non-US populations free of cardiovascular disease.
      METHODS: We reviewed studies that evaluated the performance of the Framingham
      risk score to predict first coronary events in a validation cohort, as identified
      by Medline, EMBASE, BIOSIS, and Cochrane library searches (through August 2005).
      Two reviewers independently assessed 1496 studies for eligibility, extracted
      data, and performed quality assessment using predefined forms. RESULTS: We
      included 25 validation cohorts of different population groups (n = 128,000) in
      our main analysis. Calibration varied over a wide range from under- to
      overprediction of absolute risk by factors of 0.57 to 2.7. Risk prediction for 7
      cohorts (n = 18658) from the United States, Australia, and New Zealand was well
      calibrated (corresponding figures: 0.87-1.08; for the 5 biggest cohorts). The
      estimated population risks for first coronary events were strongly associated
      (goodness of fit: R2 = 0.84) and in good agreement with observed risks
      (coefficient for predicted risk: beta = 0.84; 95% CI 0.41-1.26). In 18 European
      cohorts (n = 109499), the corresponding figures indicated close association (R2 =
      0.72) but substantial overprediction (beta = 0.58, 95% CI 0.39-0.77). The risk
      score was well calibrated on the intercept for both population clusters.
      CONCLUSION: The Framingham score is well calibrated to predict first coronary
      events in populations from the United States, Australia, and New Zealand.
      Overestimation of absolute risk in European cohorts requires recalibration
      procedures.

PMID- 17452146
TI  - Bringing cardiovascular cell-based therapy to clinical application: perspectives
      based on a National Heart, Lung, and Blood Institute Cell Therapy Working Group
      meeting.
AB  - This article reviews the progress in cell therapy for cardiovascular disease and
      examines the opportunities to accelerate the process to clinical application. It
      draws from a meeting of the National Heart, Lung, and Blood Institute Working
      Group on Translation of Cell-based Therapies for Cardiovascular Disease in August
      2004 to assess the status of clinical studies of cell-based therapies for
      cardiovascular disease, to determine the gaps in knowledge and barriers that
      prevent the implementation of well-designed and safe clinical studies, and to
      identify the areas of opportunity to apply cell-based therapies for
      cardiovascular disease to facilitate the clinical implementation of cell-based
      therapies for cardiovascular disease. We present the perspectives of experts in
      stem cell biology, cardiovascular physiology, cardiology, clinical research, and
      regulatory issues confronting the field of cell therapy for cardiovascular
      disease.

PMID- 17452147
TI  - The Cobalt chromium STent with Antiproliferative for Restenosis II (COSTAR II)
      trial study design: advancing the active-control evaluation of second-generation
      drug-eluting stents.
AB  - BACKGROUND: Randomized clinical trials have demonstrated the superiority of drug
      eluting stents (DESs) compared with bare-metal stents in reducing the need for
      revascularization and major adverse cardiac events (MACEs) in low-risk patients
      with single-vessel lesions. Rapid DES uptake has necessitated shifting the
      paradigm to active DES-controlled noninferiority study models with most studies
      using surrogate angiographic measurements to attain adequate statistical power.
      No previous prospective trial has specifically compared a new DES with an active
      control DES in a high-risk patient population using primary clinical end points.
      OBJECTIVE: COSTAR II is designed to compare use of the investigational Costar
      stent (Conor MedSystems, Palo Alto, CA) with the Taxus (Boston Scientific, Maple
      Grove, MN) stent in single- and multivessel percutaneous coronary intervention.
      The primary end point is the clinical composite of MACE at 8 months supported by
      consistent results in the evaluation of 8-month MACE rates in the single- and
      multivessel cohorts and of in-segment late loss in a small angiographic substudy
      at 9 months. METHODS: A total of 1700 patients, 50% with single-vessel and 50%
      with multivessel disease, are randomized in a 3:2 ratio to receive either Costar
      or Taxus stent(s) in this prospective, multicenter, noninferiority study design.
      Because no prior data were available to determine control multivessel MACE rates,
      an imputed placebo statistical analysis plan incorporating a variable delta based
      on actually observed control DES MACE rates will be implemented. The results of
      COSTAR II will provide information about a novel coronary stent device as well as
      unique data regarding both control and test DES use in more complex "real-world"
      patients.

PMID- 17452148
TI  - Meta-analysis of clinical trials on use of drug-eluting stents for treatment of
      acute myocardial infarction.
AB  - BACKGROUND: Recent trials have shown the effects of drug-eluting stents (DES) in
      treatment of acute myocardial infarction (AMI), but data on the clinical outcome
      are still incomplete. METHODS: We performed a meta-analysis of all trials
      comparing DES and bare-metal stents (BMS) in AMI. RESULTS: We found 7 randomized
      trials comparing the effects of DES and BMS in AMI, enrolling a total of 2357
      patients (1177 with DES and 1180 with BMS) with a follow-up of 8 to 12 months.
      Incidence of major cardiac events (death, myocardial infarction, or
      revascularization) was 9.3% in patients treated with DES and 17.6% in patients
      with BMS, with a relative risk (RR) of 0.53 with 95% CI 0.43 to 0.66. Incidence
      of death or myocardial infarction was similar in the two groups, occurring in
      5.8% of patients with DES and 6.9% of patients treated with BMS, with an RR of
      0.84 (95% CI 0.62-1.15). Target lesion revascularization occurred in 4.8% of DES
      and in 12.0% of BMS patients, with an RR of 0.40 (95% CI 0.30-0.54). Stent
      thrombosis occurred in 2.3% in DES versus 2.6% in BMS patients, with an RR of
      0.87 (95% CI 0.53-1.45). There was no heterogeneity among trials in any of the
      analyses (I2 = 0% for all). CONCLUSIONS: Drug-eluting stents significantly reduce
      need for revascularization in patients with AMI, without changes in incidence of
      death or myocardial infarction. Use of DES is not associated with an increased
      risk of stent thrombosis at 1-year follow-up.

PMID- 17452149
TI  - Impact of cardiac and renal dysfunction on inhospital morbidity and mortality of
      patients with acute myocardial infarction undergoing primary angioplasty.
AB  - BACKGROUND: Risk stratification of patients with ST-elevation myocardial
      infarction (STEMI) undergoing primary angioplasty is important in order to
      predict outcomes and to delineate targeted therapeutic strategies. Although the
      prognostic implications of reduced left ventricular ejection fraction (LVEF) and
      creatinine clearance (CrCl) have been recognized, the clinical and prognostic
      impact of their combination has never been prospectively evaluated. METHODS: We
      stratified 467 patients with STEMI undergoing primary angioplasty according to
      LVEF and CrCl values at admission: CrCl > 60 mL/min and LVEF > 40% (group 1, n =
      261); CrCl < or = 60 mL/min and LVEF > 40% (group 2, n = 113); CrCl > 60 mL/min
      and LVEF < or = 40% (group 3, n = 60); CrCl < or = 60 mL/min and LVEF < or = 40%
      (group 4, n = 33). RESULTS: Inhospital mortality was different in the 4 groups
      (1% in group 1, 3% in group 2, 15% in group 3, 30% in group 4) (P < .001). The
      incidence of combined end point of death, acute pulmonary edema, cardiogenic
      shock, and acute renal failure requiring mechanical support increased
      progressively from group 1 to group 4 (5%, 17%, 33%, and 48%, respectively) (P <
      .001). We found a significant gradient of risk in terms of inhospital mortality
      and combined end point when patients outcome was evaluated according to the
      presence of both normal LVEF and CrCl (group 1), impairment in only 1 of these 2
      parameters (group 2 and 3 pooled together), and combined LVEF and CrCl reductions
      (group 4). CONCLUSIONS: Reduced LVEF and CrCl are strong independent predictors
      of increased inhospital morbidity and mortality, and their combined evaluation
      provides a simple tool for early risk stratification in patients with STEMI
      treated with primary angioplasty.

PMID- 17452150
TI  - Reduction of neointimal hyperplasia after coronary stenting by pioglitazone in
      nondiabetic patients with metabolic syndrome.
AB  - BACKGROUND: This study investigates whether pioglitazone reduces neointimal
      hyperplasia after coronary stenting in nondiabetic patients with metabolic
      syndrome (MS) using intravascular ultrasound (IVUS). Pioglitazone, a novel
      insulin-sensitizing thiazolidinedione, has been shown to reduce neointimal
      hyperplasia after coronary stenting in patients with type 2 diabetes. However,
      the effect of pioglitazone on in-stent restenosis in nondiabetic patients with MS
      remains unknown. METHODS AND RESULTS: Twenty-eight nondiabetic patients with MS
      after bare-metal stent implantation were randomized to 6-month treatment with or
      without 30 mg/d of pioglitazone (pioglitazone group [PIO] of 14 patients with 16
      lesions and control group [CONT] of 14 patients with 16 lesions). At baseline and
      at 6-month follow-up, assessment of insulin resistance and visceral fat
      accumulation, quantitative coronary angiographic analysis, and IVUS measurements
      were performed. Pioglitazone treatment improved insulin resistance and decreased
      visceral fat accumulation without significant changes in plasma glucose levels,
      glycosylated hemoglobin A1c levels, and lipid profiles. Intimal index (intimal
      area/stent area) and intimal area were reduced in PIO compared with CONT (13% +/-
      7% vs 21% +/- 13%, P = .033; 1.28 +/- 0.76 mm2 vs 1.90 +/- 1.16 mm2, P = .084;
      respectively). Binary restenosis rate was 0% in PIO versus 31% in CONT (P =
      .043). CONCLUSIONS: This is the first randomized, prospective IVUS study
      demonstrating that pioglitazone reduces neointimal hyperplasia after coronary
      stenting in nondiabetic patients with MS. Our data suggest that pioglitazone
      treatment may represent a novel therapeutic tool to target in-stent restenosis in
      nondiabetic patients with MS.

PMID- 17452151
TI  - Early invasive versus conservative treatment in patients with failed fibrinolysis
      -no late survival benefit: the final analysis of the Middlesbrough Early
      Revascularisation to Limit Infarction (MERLIN) randomized trial.
AB  - BACKGROUND: Early (30 days) and midterm (6 months) clinical outcomes in trials
      comparing rescue angioplasty (rescue percutaneous coronary intervention [rPCI])
      with conservative treatment of failed fibrinolysis complicating ST-segment
      elevation myocardial infarction have shown variable results. Whether early rPCI
      confers late (up to 3 years) clinical benefits is not known. METHODS: The MERLIN
      trial compared rPCI and a conservative strategy in patients with failed
      fibrinolysis complicating ST-segment elevation myocardial infarction. Three
      hundred seven patients with electrocardiographic evidence of failure to reperfuse
      at 60 minutes were included. Patients in cardiogenic shock were excluded. Thirty
      day and 1-year results have been reported. Results of 3 years of follow-up are
      presented. RESULTS: Three-year mortality in the conservative arm and rPCI,
      respectively, was 16.9% versus 17.6% (P = .9, relative difference [RD] -0.8, 95%
      CI [-9.3 to 7.8]). Death rates were similar (3.9% vs 3.2%) between 1- and 3-year
      follow-up, respectively. The incidence of the composite secondary end point of
      death, reinfarction, stroke, unplanned revascularization, or heart failure was
      significantly higher in the conservative arm (64.3% vs 49%, P = .01, RD 15.3, 95%
      CI [4.2-26]). There was no significant difference in the rate of reinfarction
      (0.7% vs 0.7%) or heart failure (1.3% vs 2.7%) between 1 and 3 years between the
      conservative and rPCI arms, respectively. The incidence of subsequent unplanned
      revascularization at 3 years was significantly higher in the conservative arm
      (33.8% vs 14.4%, P < .01, RD 19.4, 95% CI [10-28.7]), most of which occurred
      within 1 year; the rates between 1 and 3 years were 3.9% in the conservative arm
      versus 2% in the rPCI arm. There was a trend toward fewer strokes in the
      conservative arm at 3 years (conservative arm 2.6% vs rPCI 6.5%, P = .1, RD 
      3.9%, 95% CI [-9.4 to 0.8]), with similar stroke rates (1.3% vs 1.3%) between 1-
      and 3-year follow-up. CONCLUSIONS: Rescue angioplasty did not confer a late
      survival advantage at 3 years. The composite end point occurred less often in the
      rPCI arm mainly because of fewer unplanned revascularization procedures in the
      early phase of follow-up. The highest risk of clinical events in patients with
      failed reperfusion is in the first year, beyond which the rate of clinical events
      is low.

PMID- 17452152
TI  - Outcome after prenatal diagnosis of tricuspid atresia: a multicenter experience.
AB  - BACKGROUND: The outcome of prenatally diagnosed tricuspid atresia (TA) is
      undefined. We sought to characterize clinical and echocardiographic features of
      fetal TA and to determine factors associated with mortality. METHODS AND RESULTS:
      All fetuses with TA (n = 88) seen at 3 tertiary care institutions from 1990 to
      2005 were reviewed. There were 58 liveborn infants (median gestational age 38
      weeks, range 24-40 weeks), 4 in utero demises, 25 terminations of pregnancy, and
      1 mother lost to follow-up. Obstruction was present at the pulmonary valve in 27
      (45%), aortic valve in 6 (10%), and aortic arch in 15 (25%). Three neonates
      received compassionate care, 1 died with multiple extracardiac anomalies, 2 were
      lost to follow-up, and 52 liveborns were actively managed with Blalock-Taussig
      shunt (23), Norwood palliation (14), pulmonary artery band (10), bidirectional
      cavopulmonary connection (3), atrial septostomy (1), and right outflow stent (1).
      Of those actively managed, there were 7 (14%) of 52 who died. Kaplan-Meier
      estimates of survival were 91% at 1 month, 87% at 6 months, and 83% at 1 year
      with no subsequent deaths for 13 years. By multivariate analysis, 2 independent
      factors were associated with an increase in time-related mortality in the
      actively managed group: presence of chromosomal anomaly or syndrome (P = .005)
      and use of extracorporeal membrane oxygenation (P = .002). CONCLUSIONS: This is
      the largest study describing TA in fetus. Compared with published observations of
      TA diagnosed postnatally, antenatal diagnosis of TA appears to have similar short
      term survival in pregnancies surviving to birth.

PMID- 17452153
TI  - Atrial septostomy improves survival in select patients with pulmonary
      hypertension.
AB  - BACKGROUND: Atrial septostomy is a palliative treatment for patients with
      pulmonary hypertension (PHTN) refractory to vasodilator therapy. Limited data
      exist in the pediatric population and in patients with repaired congenital heart
      defects. METHODS: We performed a retrospective analysis of hemodynamic and
      symptomatic changes in patients with PHTN who underwent an atrial septostomy at
      our institution. RESULTS: Forty-six atrial septostomies were performed on 43
      patients. Patient ages ranged from 0.3 to 30 years (median 12.5). Of 43 patients,
      29 had primary PHTN, 10 had PHTN associated with repaired congenital heart
      defects, and 4 had other secondary causes of PHTN. Mean baseline pulmonary
      vascular resistance was 35 +/- 17 Wood units, and mean pulmonary artery pressure
      was 74 +/- 19 mm Hg. Patients surviving > or = 30 days had immediate improvement
      in cardiac index (from 2.3 to 2.9 L x min(-1) x m(-2), P < .0001), right atrial
      pressure (RAp) (from 9.9 to 8.3 mm Hg, P < .05), and oxygen delivery (from 424 to
      491 mL O2 per minute, P < .01), with a decrease in systemic oxygen saturation
      (from 93% to 86%, P < .001). Pulmonary artery pressure was unchanged (P = .3).
      New York Heart Association class and symptoms of syncope improved (P < .01).
      Event-free survival at 1, 2, and 3 years was 84%, 77%, and 69%, respectively.
      Using the National Institutes of Health Registry model, predicted survival
      probability significantly improved (P < .001). Ten patients (22%) died within 30
      days of catheterization. Mortality was associated with preceding decompensations
      in the intensive care unit (6/10, P < .001) and a higher RAp (21.4 vs 9.8 mm Hg,
      P < .001). CONCLUSIONS: Atrial septostomy provides symptomatic and hemodynamic
      improvement in cardiac index and RAp. Risk of septostomy is increased in patients
      with preceding decompensation or a RAp > 18 mm Hg.

PMID- 17452154
TI  - Do race-specific models explain disparities in treatments after acute myocardial
      infarction?
AB  - BACKGROUND: Racial differences in healthcare are well known, although some have
      challenged previous research where risk-adjustment assumed covariates affect
      whites and blacks equally. If incorrect, this assumption may misestimate
      disparities. We sought to determine whether clinical factors affect treatment
      decisions for blacks and whites equally. METHODS: We used data from the
      Cardiovascular Cooperative Project for 130,709 white and 8286 black patients
      admitted with an acute myocardial infarction. We examined the rates of receipt of
      6 treatments using conventional common-effects models, where covariates affect
      whites and blacks equally, and race-specific models, where the effect of each
      covariate can vary by race. RESULTS: The common-effects models showed that blacks
      were less likely to receive 5 of the 6 treatments (odds ratios 0.64-1.10). The
      race-specific models displayed nearly identical treatment disparities (odds
      ratios 0.65-1.07). We found no interaction effect, which systematically suggested
      the presence of race-specific effects. CONCLUSIONS: Race-specific models yield
      nearly identical estimates of racial disparities to those obtained from
      conventional models. This suggests that clinical variables, such as hypertension
      or diabetes, seem to affect treatment decisions equally for whites and blacks.
      Previously described racial disparities in care are unlikely to be an artifact of
      misspecified models.

PMID- 17452155
TI  - Outcome after out-of-hospital cardiac arrest in a physician-staffed emergency
      medical system according to the Utstein style.
AB  - BACKGROUND: Despite a large amount of data assessing outcomes of out-of-hospital
      cardiac arrests (OHCAs), little information is available about physician-staffed
      emergency medical service (EMS) systems. The aim of our study was to investigate
      the impact of a physician on the outcome of patients after OHCA. METHODS: This is
      a prospective, observational study that included 539 consecutive patients (63.9
      +/- 19.1 years old; 349 males) with OHCA in the community of Dachau (135,000
      inhabitants) in whom resuscitation was attempted between January 2000 and January
      2006 according to Utstein style. Patients were followed up to hospital discharge.
      The primary end point of the study was that the patients was discharged alive
      from hospital. RESULTS: Of 412 patients with an OHCA, 180 (43.7%) were admitted
      to hospital, and 47 (11.4%) were discharged alive. Resuscitation was started by a
      physician in 117 (28.4%) patients, by a layperson in 118 (28.6%), or by an EMS
      personnel in 177 (43.0%). A total of 18 patients (18.6%) treated by physicians,
      13 patients (8.0%) treated by EMS personnel (P = .02 vs treatment by physician),
      and 16 patients (16.5%) resuscitated by laypersons were discharged from hospital
      (P = .8 vs treatment by physician). In 105 patients with bystander-witnessed OHCA
      of cardiac origin with shockable rhythm, the discharge rate was 32.4% (n = 34).
      Multivariate analysis identified ventricular fibrillation on first
      electrocardiogram, observed OHCA, short response time intervals but not the unit
      that performed the first resuscitation attempt as independent predictors of
      survival. CONCLUSIONS: A physician on board of the advanced life support unit was
      not identified as an independent factor of improved survival.

PMID- 17452156
TI  - Detection of pulmonary vein stenosis by transesophageal echocardiography:
      comparison with multidetector computed tomography.
AB  - OBJECTIVE: The objective of this study is to compare the use of transesophageal
      echocardiography (TEE) vs multidetector computed tomography (MDCT) for detecting
      pulmonary vein stenosis. BACKGROUND: Pulmonary vein isolation is increasingly
      used to treat atrial fibrillation. Pulmonary vein stenosis remains a potential
      complication of pulmonary vein isolation and ideal methods for detection of
      stenosis are still to be determined. METHODS: Thirty-six subjects who underwent
      pulmonary vein isolation returned for follow-up MDCT and TEE. Percent diameter
      loss was reported for each pulmonary vein stenosis by MDCT. A 50% narrowing was
      considered as an indication of a stenosis. Pulsed-wave Doppler using TEE was used
      to measure peak velocities of all pulmonary veins. RESULTS: Multidetector
      computed tomography and TEE were performed in all subjects (58 +/- 10 years) at 4
      +/- 2 months after pulmonary vein isolation. Atrial fibrillation was present in
      14% at time of follow-up. Multidetector computed tomography was able to evaluate
      all 4 (100%) pulmonary veins in 36 subjects, whereas full interrogation by TEE
      was possible in 138 (96%) of 144 veins. Pulmonary vein stenosis >50% by MDCT was
      present in 7 pulmonary veins. Analysis of the receiver operating curve for TEE
      showed that it had optimum detection of pulmonary vein stenosis at peak
      velocities approximately 100 cm/s with 86% sensitivity and 95% specificity. Area
      under the curve for TEE was 0.93. Clinically significant stenosis was observed in
      2 subjects and was detected by both TEE and MDCT. CONCLUSIONS: Transesophageal
      echocardiography was able to detect most pulmonary veins with good sensitivity
      and specificity in comparison to MDCT. Pulmonary veins may be visualized more
      frequently by MDCT; however, TEE provides additional data about the functional
      significance of a pulmonary vein stenosis.

PMID- 17452157
TI  - Polytetrafluoroethylene graft calcification in patients with surgically repaired
      congenital heart disease: evaluation using multidetector-row computed tomography.
AB  - BACKGROUND: Noninvasive determination of calcified prosthetic
      polytetrafluoroethylene (PTFE) is important in improving risk stratification. The
      purpose of this study is to assess the feasibility of multidetector-row computed
      tomography (MDCT) for the evaluation of PTFE calcification in patients with
      surgically repaired congenital heart disease and to evaluate the development and
      characteristics of calcification for specific surgical procedures. METHODS:
      Seventy-six implanted PTFE grafts in 47 patients were evaluated by MDCT
      (Aquillion 16, Toshiba Corporation, Tokyo, Japan). Explanted PTFE grafts were
      evaluated histologically in 4 patients who underwent reoperation after MDCT
      scans. RESULTS: Calcification of prosthetic PTFE was detected in 5 of 29 cases
      (17%) for ventricular septal defect (VSD) patches, 26 of 32 (81%) for right
      ventricular outflow tract (RVOT) prosthesis, 2 of 8 (25%) for atrial septal
      patches of the Fontan procedure, and 7 of 7 (100%) for extracardiac conduits of
      total cavopulmonary connection. The CT attenuation of PTFE revealed significantly
      different values for VSD patches (114 +/- 61 Hounsfield units [HU]), RVOT
      prosthesis (243 +/- 132 HU), atrial septal patches (163 +/- 161 HU), and
      extracardiac conduits (230 +/- 29 HU) (P < .0001). The CT density value of VSD
      patches was significantly lower than those of RVOT grafts and extracardiac
      conduits (P < .05). The MDCT findings were consistent with histologic analysis in
      the evaluation of calcification. CONCLUSIONS: This study demonstrates that MDCT
      enables the evaluation of prosthetic PTFE graft calcification; PTFE grafts in 4
      different implantation sites demonstrated distinctive features and the prevalence
      of calcification.

PMID- 17452158
TI  - Relationship and prognostic value of coronary artery calcification by electron
      beam computed tomography to stress-induced ischemia by single photon emission
      computed tomography.
AB  - BACKGROUND: Stress single photon emission computed tomography (SPECT) is commonly
      performed in patients with abnormal electron beam computed tomography (EBCT) to
      define risk stratification, but the published prognostic data for patients
      undergoing both SPECT and EBCT are limited. The objective of the study was to
      examine the association and prognostic value between EBCT, coronary artery
      calcium score (CACS), and stress SPECT imaging. METHODS: We identified 835
      patients (age 54.8 +/- 10.0 years, 77% male) who underwent EBCT and stress SPECT
      within a 3-month period. Coronary artery calcium score was categorized as normal
      (0), minimal (1-10), mild (11-100), moderate (101-400), and severe (>400). Single
      photon emission computed tomography summed stress score (SSS) was categorized as
      normal, low risk, intermediate risk, and high risk per Cedar Sinai criteria.
      Average follow-up was 4.8 +/- 3.2 years. End points were all-cause death,
      death/myocardial infarction (MI), and death/MI/late revascularization. RESULTS:
      The correlation of CACS to SSS was weak but statistically significant (r = +0.19,
      P < .001). The percentage of high-risk SSS increased with higher CACS scores; 4%
      of patients with normal EBCT and 18% with severe CACS had high-risk SSS. Coronary
      artery calcium score (chi2 = 11.4, P < .001), diabetes mellitus (chi2 = 4.6, P =
      .031), and chest pain class (chi2 = 8.7, P = .003) were independently associated
      with high-risk SPECT. The SSS (chi2 = 6.9, P = .009) and CACS (chi2 = 7.8, P =
      .005) were independently associated with mortality, as well as with both
      secondary end points of death/MI and death/MI/late revascularization. Only CACS
      predicted mortality in the 408 asymptomatic patients (chi2 = 5.2, P = .02), but
      these patients had an annual mortality of only 0.4% over the next 5 years.
      CONCLUSIONS: In selected patients undergoing both EBCT and SPECT, CACS is weakly
      correlated with SPECT SSS, likely reflecting the different information provided
      by EBCT and SPECT. Coronary artery calcium score is independently associated with
      high-risk SPECT after adjustment for clinical variables. Coronary artery calcium
      score and SSS are complementary for the prediction of mortality in symptomatic
      patients. Only CACS predicted mortality in the asymptomatic patients, but they
      had a low annual mortality.

PMID- 17452159
TI  - Prospective assessment after pediatric cardiac ablation: fate of intracardiac
      structure and function, as assessed by serial echocardiography.
AB  - BACKGROUND: Catheter ablation puts cardiac valves at risk of damage, and children
      are of particular concern. METHODS: A multicenter prospective study was performed
      to assess the results and risks associated with radiofrequency (RF) ablation in
      children. Patients were aged 0 to 16 years with supraventricular tachycardia due
      to accessory pathway or atrioventricular node reentry, excluding patients with
      more than trivial congenital heart disease. A total of 481 patients were
      recruited into the prospective cohort and were followed up at 2, 6 and, 12 months
      after ablation. Complete echocardiograms were obtained before and at intervals
      after RF ablation, and they were reviewed by experts who were blinded with
      respect to diagnosis, outcome, pathway site, and study interval. RESULTS:
      Moderate valve insufficiency was quite rare (0.12%), but mild insufficiency was
      common, both before ablation (42.43%) and at 2 months after ablation (40.49%).
      Analysis of paired readings failed to demonstrate a tendency toward increased
      insufficiency of valves adjacent to ablation targets, with the exception of the
      tricuspid valve after the ablation of right freewall pathways and
      atrioventricular node reentry, but the degree of change was small. No clear
      changes in left ventricular systolic or diastolic function were observed, and
      dyskinesis was rare and not related to the ablation target. No intracardiac
      thrombosis was observed. CONCLUSIONS: Serious injury to cardiac valves due to RF
      ablation is very rare, but the tricuspid valve may be mildly affected in some
      cases. We identified no clear effect of RF ablation on cardiac wall motion or on
      left ventricular function.

PMID- 17452160
TI  - Effect of the G-308A polymorphism of the tumor necrosis factor alpha gene on the
      risk of ischemic heart disease and ischemic stroke: a meta-analysis.
AB  - BACKGROUND: Under the hypothesis that the G-308A polymorphism in the promoter
      region of the tumor necrosis factor alpha gene might increase tumor necrosis
      factor alpha expression, several investigations have been performed to examine
      the influence of the -308A allele on the risk of cardiovascular events. The
      results of these studies, however, have been conflicting. To provide a more
      robust estimate of the putative effect of the G-308A polymorphism on the risk of
      cerebrocardiovascular events, we did 2 meta-analyses that examined the role of
      the -308A variant in both ischemic heart disease (IHD) and ischemic stroke.
      METHODS: We applied both fixed- and random-effects models to combine odds ratios
      (OR) and 95% CIs, and publication bias and heterogeneity were explored. RESULTS:
      Data of 17,030 subjects from 23 studies were used. Overall, in populations
      predominantly of European ancestry, no association between the G-308A
      polymorphism and IHD under a dominant model (AA + GA vs GG) was observed: OR,
      1.07; 95% CI, 0.94-1.21; P = .32. Similarly, the -308A allele was not associated
      with ischemic stroke considering all studies: OR, 0.99; 95% CI, 0.70-1.41, P =
      .96. However, analysis by ancestry revealed that Asian subjects harboring the 
      308A variant were approximately 40% less likely to have stroke compared to the GG
      genotype: OR, 0.62; 95% CI, 0.44-0.86; P = .004. CONCLUSIONS: These results
      suggest that the G-308A polymorphism is unlikely to be associated with the
      development of IHD, whereas it might be a protective factor for ischemic stroke
      in Asians only.

PMID- 17452161
TI  - Long-term survival after successful inhospital cardiac arrest resuscitation.
AB  - BACKGROUND: Little is known about long-term outcomes of patients who survive
      inhospital cardiac arrest. METHODS: We examined long-term survival after
      inhospital cardiac arrest and whether procedural changes that improved survival
      to discharge impacted long-term survival. Consecutive inhospital arrests in the
      Atlanta Veterans Affairs Medical Center (Atlanta, GA) from 1995 to 2004 (n = 732)
      were retrospectively analyzed. Data regarding the arrest was obtained, including
      age, left ventricular ejection fraction, medications, and comorbidities,
      presenting rhythm, location of arrest, code duration, and outcomes. Long-term
      mortality data was obtained based on chart and Social Security Death Index
      reviews. Further data was gathered on internal cardioverter-defibrillator
      presence and use in survivors. RESULTS: Overall, 49 subjects (6.6%) survived to
      discharge. Univariate analysis found that ventricular tachycardia/ventricular
      fibrillation and the use of beta-blockers, angiotensin-converting enzyme
      inhibitors, and antiarrhythmics at the time of arrest were associated with
      increased survival, whereas advancing age and comorbidities were associated with
      a higher risk of mortality. Multivariate analysis determined that age, rhythm,
      and comorbidities independently affected survival. Implementation of a
      resuscitation program previously documented to improve survival to discharge did
      not translate to durable long-term survival. Three-year survival rate after
      discharge was only 41%. Alternatively, subjects with internal cardioverter
      defibrillator showed a 36% improvement in 3-year survival rate to 77% (P = .001).
      CONCLUSIONS: Subjects with inhospital cardiac arrest have poor long-term
      prognoses. A strategy that improved inhospital survival did not alter long-term
      mortality rate. Thus, survival to discharge may not be a sufficient end point for
      future resuscitation trials.

PMID- 17452162
TI  - Absence of bilateral vision loss from amiodarone: a randomized trial.
AB  - BACKGROUND: Amiodarone's role as a cause of toxic optic neuropathy is based on
      case reports. Annual frequency estimates of 0.36% to 2.0%, which have been made
      without reference to the dose or duration of treatment, are 12 to 200 times
      higher than those for idiopathic nonarteritic anterior ischemic neuropathy. The
      object of this study was to determine the incidence, dose, and time until onset
      of bilateral vision loss from amiodarone as a secondary end point in an
      investigation of amiodarone's role in preventing sudden death. METHODS:
      Randomized subjects received body weight-determined doses of closed-label
      amiodarone (n = 837) or placebo (n = 832) in a prospective double-masked manner.
      Closed-label amiodarone subjects were followed, unless death occurred, for a
      minimum of 27 months. Median follow-up in survivors was 45.5 months. The end
      point was removal from the study because of bilateral vision loss. RESULTS: No
      subject was removed from the study because of bilateral vision loss. Subjects
      receiving continuous amiodarone for 4 to >60 months at daily doses of >2.0 mg/kg
      (n = 696), >3.0 mg/kg (n = 559), or >4.0 mg/kg (n = 219) had maximum possible
      (95% confidence) annual incidences of bilateral toxic vision loss of 0.23%,
      0.29%, or 0.74%, respectively. The maximum possible annual incidence rate of
      bilateral vision loss from amiodarone in all 837 subjects (median age 60 years)
      receiving a mean daily dose of 3.7 mg/kg (300 mg) was 0.13%. CONCLUSIONS: At the
      doses commonly used clinically, bilateral vision loss from amiodarone toxic optic
      neuropathy occurs infrequently, if at all.

PMID- 17452163
TI  - Improvement in diastolic function and left ventricular filling pressure induced
      by cardiac resynchronization therapy.
AB  - BACKGROUND: Variable results of cardiac resynchronization therapy (CRT) on
      diastolic function have been described. We investigated 3 and 12 months' effect
      of CRT on diastolic function and left ventricular (LV) filling pressures and
      their relation to LV reverse remodeling. METHODS: Fifty-two patients' (36 male,
      69 +/- 8 years, QRS duration 170 +/- 29 milliseconds) echo-Doppler was performed
      before and 3 and 12 months after CRT. Tissue Doppler early diastolic annular (Em)
      and color M-mode-derived flow propagation (Vp) velocities were used to estimate
      LV filling pressures by E/Em and E/Vp ratios. RESULTS: After 12 months, LV
      reverse remodeling (end-systolic volume decrease >15%) was observed in 58%.
      Despite a significantly more compromised baseline diastolic function of patients
      without LV reverse remodeling, multivariate analysis revealed that only LV
      dyssynchrony could predict LV reverse remodeling. Grades 2 and 3 diastolic
      function improved only in LV reverse remodeling patients (from 34% to 13% to
      10%), whereas a nonsignificant increase from 59% to 67% to 72% was observed in
      patients without reverse remodeling. Irrespective of LV volume response, short
      term symptomatic benefit was related to decreased filling pressure. However,
      after 12 months, E/Em and E/Vp only significantly decreased in patients with LV
      reverse remodeling (from 16.0 +/- 6 to 10.4 +/- 4 and 2.2 +/- 0.6 to 1.5 +/- 0.4,
      respectively). CONCLUSIONS: Left ventricular reverse remodeling induced by CRT is
      accompanied by improvement in diastolic function and estimated LV filling
      pressure. Short-term symptomatic benefit was related to decreased filling
      pressure. However, for longer-term symptomatic improvement and decreased filling
      pressures, LV reverse remodeling appeared mandatory.

PMID- 17452164
TI  - Detection of viral genome in the myocardium: lack of prognostic and functional
      relevance in patients with acute dilated cardiomyopathy.
AB  - BACKGROUND: The presence of viral genome in the myocardium of patients with
      dilated cardiomyopathy (DCM) has been suggested as causative for the underlying
      cardiac disease. Nevertheless, the results of present studies are conflicting
      regarding the natural course of heart diseases associated with detection of viral
      genome. This study was undertaken to determine if the detection of viral genome
      in the myocardium of patients with DCM is of functional and prognostic relevance
      under modern treatment strategies of heart insufficiency. METHODS: In 197
      patients with DCM, left ventricular endomyocardial biopsies were performed.
      Analysis for genome of adenovirus, enterovirus (EV), and parvovirus B19 as well
      as enteroviral replication and immunohistology was performed. RESULTS: The
      increase in ejection fraction (EF) was 14.5 +/- 12.4% in the EV-positive group
      compared with 11.1 +/- 14.2 in the EV-negative group (P = not significant [NS])
      after a mean follow-up (FU) of 19.5 and 17.6 months. The increase in EF in the
      virus-positive group (positive for EV, adenovirus, or parvovirus B19) was 15.3 +/
      13.3% compared with 12.3 +/- 11.9% in the virus-negative group (P = NS) after a
      mean FU of 17.6 and 11.5 months. There was no significant difference in the
      change of EF between the EV-positive and virus-negative groups. Detection of
      enteroviral RNA replication (detection of EV minus-strand RNA) did not result in
      a deterioration of left ventricular function compared with the virus-negative
      group (P = NS) after mean FU of 11.2 and 12.0 months. The transplantation-free
      survival of the patients was not influenced by detection of viral genome.
      CONCLUSIONS: Our results favor the view that the presence of viral genome in the
      myocardium of patients with DCM is of no functional and prognostic relevance.

PMID- 17452165
TI  - Exercise oscillatory breathing and increased ventilation to carbon dioxide
      production slope in heart failure: an unfavorable combination with high
      prognostic value.
AB  - BACKGROUND: Increased slope of exercise ventilation to carbon dioxide production
      (VE/VCO2) is an established prognosticator in patients with heart failure.
      Recently, the occurrence of exercise oscillatory breathing (EOB) has emerged as
      an additional strong indicator of survival. OBJECTIVE: The aim of this study is
      to define the respective prognostic significance of these variables and whether
      excess risk may be identified when either respiratory disorder is present.
      METHODS: In 288 stable chronic HF patients (average left ventricular ejection
      fraction, 33 +/- 13%) who underwent cardiopulmonary exercise testing, the
      prognostic relevance of VE/VCO2 slope, EOB, and peak VO2 was evaluated by
      multivariate Cox regression. RESULTS: During a mean interval of 28 +/- 13 months,
      62 patients died of cardiac reasons. Thirty-five percent presented with EOB.
      Among patients exhibiting EOB, 54% had an elevated VE/VCO2 slope. The optimal
      threshold value for the VE/VCO2 slope identified by receiver operating
      characteristic analysis was < 36.2 or > or = 36.2 (sensitivity, 77%; specificity,
      64%; P < .001). Univariate predictors of death included low left ventricular
      ejection fraction, low peak VO2, high VE/VCO2 slope, and EOB presence.
      Multivariate analysis selected EOB as the strongest predictor (chi2, 46.5; P <
      .001). The VE/VCO2 slope (threshold, < 36.2 or > or = 36.2) was the only other
      exercise test variable retained in the regression (residual chi2, 5.9; P = .02).
      The hazard ratio for subjects with EOB and a VE/VCO2 slope > or = 36.2 was 11.4
      (95% confidence interval, 4.9-26.5; P < .001). CONCLUSION: These findings
      identify EOB as a strong survival predictor even more powerful than VE/VCO2
      slope. Exercise oscillatory breathing presence does not necessarily imply an
      elevated VE/VCO2 slope, but combination of either both yields to a burden of risk
      remarkably high.

PMID- 17452166
TI  - A double-blind placebo-controlled pilot study of controlled-release paroxetine on
      depression and quality of life in chronic heart failure.
AB  - BACKGROUND: Depression is frequently observed in patients with heart failure and
      is associated with poor quality of life and adverse prognosis. However, the
      prevalence of depression in heart failure could be overestimated because symptoms
      of depression overlap with those of heart failure. Similarly, the importance of
      depression may be overestimated if depression merely reflects worse heart
      failure. Because the response to depression treatment has not been evaluated in
      this patient population, we evaluated the efficacy of controlled-release
      paroxetine (paroxetine CR), a selective serotonin reuptake inhibitor, on
      depression and quality of life in chronic heart failure. METHODS: A double-blind,
      randomized, placebo-controlled design was used to evaluate reductions in
      depression following 12 weeks of treatment with paroxetine CR (n = 14, age 62.1
      +/- 12.3 years) or placebo (n = 14, age = 61.9 +/- 9.0 years). Patients with
      symptomatic congestive heart failure and a score of at least 10 on the Beck
      Depression Inventory (BDI) were eligible. Beck Depression Inventory was obtained
      at baseline and 4, 8, and 12 weeks of follow-up. Quality of life was assessed
      using the Medical Outcomes Study Short Form and the Minnesota Living with Heart
      Failure Questionnaire. RESULTS: Controlled-release paroxetine resulted in
      significantly more recovery from depression (BDI <10) than placebo (69% vs 23%, P
      = .018) and resulted in lower continuous BDI scores throughout the intervention
      (P = .024). Controlled-release paroxetine was associated with higher general
      health levels compared with placebo on the Medical Outcomes Study 36-Item Short
      Form survey (38 +/- 10 vs 30 +/- 6, P = .016) at 12 weeks of follow-up.
      Reductions in depression were correlated with improvements in psychological
      aspects of quality of life (P < .05) but not with physical quality of life
      measures (P > .10). CONCLUSION: Antidepressant therapy with paroxetine CR results
      in significant reductions in depression among patients with heart failure. The
      reductions in depression with paroxetine CR are accompanied by improvements in
      psychological aspects of quality of life. Larger controlled trials are needed to
      further document the effectiveness of paroxetine CR and other selective serotonin
      reuptake inhibitors in patients with heart failure and to determine patient
      subgroups that are most likely to benefit from antidepressive interventions.

PMID- 17452167
TI  - Results from a phase II multicenter, double-blind placebo-controlled study of Del
      1 (VLTS-589) for intermittent claudication in subjects with peripheral arterial
      disease.
AB  - BACKGROUND: This study compared VLTS-589 (plasmid encoding the angiomatrix
      protein Del-1 in conjunction with poloxamer 188) with poloxamer 188 control, for
      the treatment of intermittent claudication in patients with moderate to severe
      peripheral arterial disease. METHODS: Subjects with bilateral intermittent
      claudication and peak walking time (PWT) between 1 and 10 minutes on 2 qualifying
      (reproducible; within 25% of each other) treadmill tests were enrolled. Patients
      received VLTS-589 or poloxamer 188 control, administered as 21 intramuscular
      injections to each lower extremity (42 mL in each extremity). In addition to
      safety and tolerability, efficacy evaluations compared to baseline included the
      following: change in PWT at 90 days (primary end point), change in claudication
      onset time, change in ankle brachial index (ABI), and change in quality of life
      measures. RESULTS: A total of 105 patients were randomized and treated. During
      the 30, 90, and 180 days follow-up, mean PWT, claudication onset time, and ABI
      were significantly increased compared to baseline values in both treatment groups
      with no significant difference between groups in the primary or secondary end
      points. In addition, both groups demonstrated significantly improved quality of
      life at follow-up vs baseline, with no significant differences between groups.
      Serious adverse events were similar in both groups--none were definitely
      treatment-related. CONCLUSION: Intramuscular delivery of both Del-1 expressing
      plasmid and the control resulted in significant improvement in exercise capacity
      compared to baseline at 30, 90, and 180 days. There was no difference in outcome
      measures associated with the Del-1 plasmid.

PMID- 17452169
TI  - Does "off-label" mean off limits for patient care?

PMID- 17452168
TI  - Elevated ICAM-1 and MCP-1 plasma levels in subjects at high cardiovascular risk
      are diminished by atorvastatin treatment. Atorvastatin on Inflammatory Markers
      study: a substudy of Achieve Cholesterol Targets Fast with Atorvastatin
      Stratified Titration.
AB  - BACKGROUND: Plasma levels of soluble intercellular adhesion molecule 1 (sICAM-1)
      and monocyte chemoattractant protein 1 (sMCP-1) are associated with increased
      risk for future coronary events. However, the effect of statins on these
      inflammatory markers has hardly been studied. We analyzed whether treatment with
      the different doses of atorvastatin affects sICAM-1 and sMCP-1 plasma levels in
      subjects at high cardiovascular risk. METHODS: Achieve Cholesterol Targets Fast
      with Atorvastatin Stratified Titration was a 12-week, prospective, multicenter,
      open-label trial that enrolled a total of 2117 subjects with coronary heart
      disease (CHD), CHD equivalent (defined as diabetes, peripheral vascular disease,
      or cerebrovascular disease), or a 10-year CHD risk >20%. Subjects with low
      density-lipoprotein cholesterol between 100 and 220 mg/dL (2.6-5.7 mmol/L) and
      triglycerides <600 mg/dL (6.8 mmol/L) were assigned to atorvastatin (10-80 mg/d)
      based on low-density-lipoprotein cholesterol at screening. The Atorvastatin on
      Inflammatory Markers study included statin-free patients (N = 1078). RESULTS: At
      baseline, 52%, 14%, 12%, and 22% of subjects were assigned to doses of 10, 20,
      40, and 80 mg, respectively. Levels of sICAM-1 [geometric mean (95% confidence
      interval); 283.8 (278.1-289.6) vs 131.9 (127.2-136.6) ng/mL, P < .0001] and sMCP
      1 [164.1 (159.9-168.2) vs 131.1 (123.1-139.6 pg/mL, P < .0001] were increased in
      subjects at high cardiovascular risk compared to healthy subjects (n = 130). In
      the whole population, sICAM-1 and sMCP-1 levels were reduced by atorvastatin [%
      change (95% confidence interval); -2.2 (-3.8 to -0.6); -4.1 (-6.1 to -2); P =
      .006 and P = .0002, respectively]. All doses of atorvastatin diminished sICAM-1
      and sMCP-1 levels in the highest quartile. CONCLUSIONS: Short treatment with
      atorvastatin reduced sICAM-1 and sMCP-1 plasma levels showing anti-inflammatory
      effects in subjects at high cardiovascular risk.

PMID- 17452170
TI  - Congruency in homonymous hemianopia.

PMID- 17452171
TI  - An international strategic plan to preserve and restore vision: four curricula of
      ophthalmic education.
AB  - PURPOSE: To highlight the four International Curricula of Ophthalmic Education
      developed by the Task Forces of the International Council of Ophthalmology,
      published in Klinische Monatsblatter fur Augenheilkunde in November 2006. DESIGN:
      A global perspective of developing educational curricula as tools to improve eye
      care. METHODS: Review of the experience and conclusions of the four international
      panels. RESULTS: The Task Force on Resident and Specialist Education developed a
      curriculum consisting of 15 topics in basic, standard, and advanced levels to
      provide flexibility of educational programs of the ophthalmic specialist in
      different locations across the world. The curricula were designed to be an
      educational tool to stimulate multiple levels of training of the ophthalmic
      specialist. The Task Force on Ophthalmic Education of Medical Students designed a
      curriculum covering 11 topics and provides illustrative materials for teachers
      and students. The Task Force strongly advocates the ophthalmology curriculum to
      be part of the core program of general medical schools education. The Task Force
      on Para-ophthalmic Vision Specialist Education developed a curriculum to
      highlight the importance of a team approach to eye care, consisting of ophthalmic
      specialists and paraophthalmic personnel to produce maximum efficiency. The Task
      Force on Continuing Medical Education (CME) designed a curriculum exploring the
      principles, elements, categories, and administration of CME activities in a
      variety of topics. CONCLUSIONS: These curricula shifted the traditional
      apprentice system of education to a curriculum-based training program in which
      goals, expectations, competencies, and technical training are defined to improve
      eye care worldwide.

PMID- 17452172
TI  - Comparison of a five-degree visual field between two programs of different
      testing field range.
AB  - PURPOSE: A five-degree visual field with two programs of different testing field
      size was studied, and the visual fields between them were compared. DESIGN:
      Observational study. METHODS: Forty-six patients with open-angle glaucoma were
      tested by Humphrey field analyzer (Carl Zeiss Meditec, Inc, Dublin, California,
      USA) programs 30-2 full threshold and 10-2 full threshold. Forty reliable results
      with both programs were analyzed. RESULTS: Sensitivity of the same position
      within a five-degree field was significantly higher with the 10-2 program than
      with the 30-2 program. Higher sensitivity within a five-degree field with the 10
      2 program significantly correlated with that with the 30-2 program. CONCLUSIONS:
      Visual field determined by automated perimetry was influenced by testing field
      size.

PMID- 17452173
TI  - The impact of glaucoma coding in a large claims database.
AB  - PURPOSE: Coding variation and its impact on identified populations is a major
      concern in database analyses. We assessed potential differences in demographics
      and healthcare charges among patients with open-angle glaucoma identified through
      different International Classification of Diseases, Ninth Revision (ICD-9) coding
      algorithms. DESIGN: Retrospective database analysis. METHODS: Three glaucoma
      cohorts were identified based on hierarchical inclusion of patients with >/=2
      glaucoma ICD-9 codes (PharMetrics, Inc, Watertown, Massachusetts, USA, 1998 to
      2003). Descriptive statistics and healthcare charges were assessed for each
      cohort. RESULTS: The three cohorts included 64,380, 14,705, and 4,225 unique
      patients each. Although significant differences in age, gender, region, payer
      type, product type, and medical comorbidities existed among the three cohorts,
      these differences had little impact on resource consumption when the cohorts were
      combined, given the smaller number of patients outside of the primary cohort.
      CONCLUSIONS: Glaucoma coding variation in administrative data sets has limited
      impact on analyses of resource consumption among open-angle glaucoma patients.

PMID- 17452174
TI  - Rates of glaucoma medication utilization among older adults with suspected
      glaucoma, 1992 to 2002.
AB  - PURPOSE: To determine rates of glaucoma medication utilization among glaucoma
      suspects in the Medicare Current Beneficiary Survey (MCBS) and identify recent
      utilization patterns for various hypotensive drug classes. DESIGN: Cohort study.
      METHODS: By using MCBS data between 1992 and 2002 merged with Medicare claims
      data, utilization rates for glaucoma medication classes were calculated for
      survey participants >/=65 years with suspected glaucoma. Utilization trends over
      the 11-year period were identified. RESULTS: Each year, more than 85% of glaucoma
      suspects used no hypotensive medications. Between 1992 and 2002, utilization
      rates decreased substantially for beta-blockers and miotics and increased for
      alpha-agonists, combination beta-blockers-carbonic-anhydrase inhibitors, and
      prostaglandin analogues. CONCLUSION: This study identifies recent changes in
      patterns of glaucoma suspects' use of hypotensive medications by using patient
      reported information, thus avoiding reliance on third-party databases. Such
      trends over time are important to recognize, because they reflect variations in
      patient care and have economic and clinical implications.

PMID- 17452175
TI  - Anterior segment optical coherence tomography imaging of trabeculectomy blebs
      before and after laser suture lysis.
AB  - PURPOSE: To image trabeculectomy blebs before and after laser suture lysis (LSL)
      using anterior segment optical coherence tomography (AS-OCT). DESIGN: Prospective
      observational study. METHODS: Blebs were imaged with a prototype of the AS-OCT
      (Carl Zeiss Meditec, Inc, Dublin, California, USA) before and after LSL. Blebs
      were assessed for bleb height, bleb wall thickness, apposition of the scleral
      flap to sclera, and patency of the internal ostium. RESULTS: Seven blebs in eyes
      of seven patients were imaged. Pre-LSL, five blebs were low and two were of
      moderate height. After LSL, six of seven eyes (85.7%) showed an increase in total
      bleb height, with increased bleb wall thickness and separation of the scleral
      flap from sclera. In one eye, there was no discernible change in bleb height,
      cavity height, or wall thickness. CONCLUSIONS: AS-OCT was able to demonstrate
      features of bleb morphology that changed after LSL.

PMID- 17452176
TI  - Relationship between foveal threshold and visual acuity using the Humphrey visual
      field analyzer.
AB  - PURPOSE: Evaluate Humphrey visual field (VF) analyzer central 30-2 foveal
      threshold test for best-corrected visual acuity. DESIGN: Consecutive case series.
      METHODS: Both eyes (n = 117) of 59 patients with diseased and healthy eyes
      presenting for VF analysis were evaluated to determine foveal threshold. This was
      compared with uncorrected visual acuity converted to logMAR, determined by
      manifest refraction, or estimated from Snellen visual acuity with pinhole.
      RESULTS: Foveal threshold correlated with logMAR uncorrected visual acuity for
      right (P < .0001) and left eyes (P < .0001) and logMAR best-corrected visual
      acuity for right (P < .0001) and left eyes (P < .0001). Sixty-eight percent of
      eyes with visual acuity <20/50 had foveal threshold of 0 to 30; 47% with visual
      acuity of >20/20 had foveal threshold better than 37. CONCLUSIONS: Foveal
      threshold measurement appears to provide a reliable estimate of best-corrected
      visual acuity. This method may usefully predict visual acuity in eyes with
      possible nonorganic visual acuity loss.

PMID- 17452177
TI  - Anterior segment optical coherence tomography for imaging the anterior chamber
      after laser peripheral iridotomy.
AB  - PURPOSE: To evaluate changes in anterior segment morphology by anterior segment
      optical coherence tomography (OCT) and gonioscopy before and after laser
      peripheral iridotomy (LPI). DESIGN: Prospective comparative observational case
      series. METHODS: Ten eyes of 10 patients with narrow angles were enrolled in the
      study. Angles were assessed by gonioscopy and anterior segment OCT pre- and post
      LPI. The angle opening distance at 500 microm, angle recess area at 500 microm
      and 750 microm, and trabecular-iris space area at 500 microm and 750 microm were
      compared pre- and post-LPI. RESULTS: The mean gonioscopy grade increased
      significantly from 0.56 to 2.6 (P < .001). All OCT parameters increased
      significantly post-LPI. CONCLUSIONS: Changes in the anterior chamber angle
      morphology post-LPI can be imaged and objectively quantified by anterior segment
      OCT.

PMID- 17452178
TI  - A method of measuring anterior chamber volume using the anterior segment optical
      coherence tomographer and specialized software.
AB  - PURPOSE: To describe and evaluate a new method for measuring anterior chamber
      volume (ACV). DESIGN: Observational case series. METHODS: The authors measured
      ACV using the anterior chamber (AC) optical coherence tomographer (OCT) and
      applied image-processing software developed by them. Repeatability was evaluated.
      The ACV was measured in patient groups with normal ACs, shallow ACs, and deep
      ACs. The volume difference before and after laser peripheral iridotomy (LPI) was
      analyzed for the shallow and deep groups. RESULTS: Coefficients of repeatability
      for intraoperator, interoperator, and interimage measurements were 0.406%,
      0.958%, and 0.851%, respectively. The limits of agreement for intraoperator and
      interoperator measurement were -0.911 microl to 1.343 microl and -7.875 microl to
      -2.463 microl, respectively. There were significant ACV differences in normal,
      shallow, and deep AC eyes (P < .001) and before and after LPI in shallow AC (P <
      .001) and deep AC (P = .008) eyes. CONCLUSIONS: The ACV values obtained by this
      method were repeatable and in accord with clinical observation.

PMID- 17452179
TI  - Ultrasound biomicroscopy study of direct and oblique 25-gauge vitrectomy
      sclerotomies.
AB  - PURPOSE: To study 25-gauge sclerotomy healing process in vivo with ultrasound
      biomicroscopy (UBM) in direct and oblique incisions. DESIGN: Prospective
      interventional case series report. METHODS: At our institution, we performed UBM
      studies on 53 sclerotomies during the first 30 days after 25-gauge vitrectomy,
      looking for conjunctival bleb development, sclerotomy healing signs, and vitreous
      incarceration in the wound. RESULTS: Echographical healing signs were completed
      in 77% of patients by day 15 with no differences between direct and oblique
      sclerotomies. By day 30, all but one sclerotomy were closed. Conjunctival blebs
      developed over 64% of direct sclerotomies, and 25% of oblique (P = .0059), but
      all resolved spontaneously by day 15. Vitreous incarceration appeared in 72% of
      sclerotomies. CONCLUSIONS: Twenty-five gauge sclerotomies heal by day 15 in most
      cases with no difference between direct and oblique sclerotomy construction.
      Conjunctival blebs developed more frequently over direct than oblique
      sclerotomies.

PMID- 17452180
TI  - Microrips of the retinal pigment epithelium in polypoidal choroidal vasculopathy.
AB  - PURPOSE: To study the clinical characteristics of microrips of the retinal
      pigment epithelium (RPE) in polypoidal choroidal vasculopathy (PCV). DESIGN:
      Retrospective case series. METHODS: For this study, we retrospectively reviewed
      156 consecutive eyes of 136 patients with PCV. The lesions were examined with
      fluorescein angiography and indocyanine green angiography. RESULTS: Of 156 eyes
      with PCV, 11 (7.1%) had microrips of the RPE at the margin of the pigment
      epithelial detachment. In the early phase of fluorescein angiography, the
      microrips showed pinpoint leakage from the RPE, which increased and pooled within
      the subretinal space in the late phase. Of the 11 eyes with microrips, the rip
      disappeared in 10 eyes (90.9%), and no eyes developed RPE tears during follow-up.
      The mean duration from the first detection of a microrip to resolution was 3.0 +/
      1.6 months. CONCLUSIONS: In eyes with PCV, microrips of the RPE are not
      uncommon, but have minimal clinical relevance.

PMID- 17452182
TI  - Severe retinal thermal injury after indocyanine green-mediated photothrombosis
      for central serous chorioretinopathy.
AB  - PURPOSE: To report severe retinal thermal damage after indocyanine green-mediated
      photothrombosis (IMP) for chronic central serous chorioretinopathy (CSC). DESIGN:
      Interventional case report. METHODS: A 31-year-old white male underwent IMP for
      chronic CSC. RESULTS: During the procedure, retinal whitening was observed in the
      area of the treatment spot. Fluorescein angiography revealed staining of the
      retinal arteries in the treated area. One year later, macular retinal pigment
      epithelial (RPE) changes were seen, accompanied by severe loss of vision.
      CONCLUSIONS: IMP has been described as a relatively safe treatment option for
      persistent CSC. However, we herein report a case in which severe retinal damage
      occurred as a consequence of the treatment. We thus alert clinicians of this
      potential adverse event.

PMID- 17452181
TI  - Purtscher-like retinopathy in a patient with HELLP syndrome.
AB  - PURPOSE: To report the antepartum presentation of Purtscher-like retinopathy and
      hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome that resulted
      in severe permanent visual loss. DESIGN: Interventional case report. METHODS: A
      25-year-old primigravida patient at 38.5 weeks gestation presented with severe
      bilateral loss of vision. Immediate hospitalization with complete evaluation,
      urgent medical treatment, and cesarean section was performed. RESULTS:
      Ophthalmoscopic evaluation showed bilateral Purtscher-like retinopathy.
      Laboratory studies revealed elevated liver enzymes, thrombocytopenia, and
      evidence of intravascular coagulation consistent with HELLP syndrome. Despite the
      successful delivery of a healthy baby, the patient developed permanent visual
      loss. CONCLUSION: Purtscher-like retinopathy with permanent visual loss can occur
      antepartum in patients with HELLP syndrome.

PMID- 17452183
TI  - Age-related macular degeneration in very old individuals with family history.
AB  - PURPOSE: To study age-related macular degeneration (AMD) in old and very old
      individuals with family history of AMD to find the proportion of those with early
      and advanced AMD. DESIGN: Retrospective cross-sectional cohort study of
      individuals with family history of AMD. METHODS: Database of 897 AMD patients
      ages 75 to 102 years with family history of AMD was compiled. Color fundus
      photographs were graded in a masked fashion according to the International
      Classification of AMD. RESULTS: With increasing age, a gradually larger
      proportion of participants had advanced AMD; 54% (469 of 863) of all those 75
      years and older had advanced AMD, 64% (258 of 406) of all those 85 years and
      older, 74% (37 of 50) of all those 95 years and older, and all (eight of eight)
      100 years and older had advanced AMD. CONCLUSIONS: All the centenarians in the
      present study had advanced AMD.

PMID- 17452184
TI  - Evaluation of a stereoscopic camera-based three-dimensional viewing workstation
      for ophthalmic surgery.
AB  - PURPOSE: To evaluate the effectiveness of a prototype stereoscopic camera-based
      viewing system (Digital Microsurgical Workstation, three-dimensional (3D) Vision
      Systems, Irvine, California, USA) for anterior and posterior segment ophthalmic
      surgery. DESIGN: Institutional-based prospective study. METHODS: Anterior and
      posterior segment surgeons performed designated standardized tasks on porcine
      eyes after training on prosthetic plastic eyes. RESULTS: Both anterior and
      posterior segment surgeons were able to complete tasks requiring minimal or
      moderate stereoscopic viewing. The results indicate that the system provides
      improved ergonomics. Improvements in key viewing performance areas would further
      enhance the value over a conventional operating microscope. CONCLUSIONS: The
      performance of the prototype system is not at par with the planned commercial
      system. With continued development of this technology, the three- dimensional
      system may be a novel viewing system in ophthalmic surgery with improved
      ergonomics with respect to traditional microscopic viewing.

PMID- 17452185
TI  - Binasal visual field defects from simultaneous bilateral retinal infarctions in
      sickle cell disease.
AB  - PURPOSE: To report a case of retinal occlusive disease producing binasal visual
      field defects in a patient with sickle cell (SC) disease. DESIGN: Retrospective
      case report. METHODS: A 21-year-old man with SC disease presented with binasal
      field defects and 20/20 acuity in each eye. RESULTS: Initial ophthalmoscopy and
      fluorescein angiography revealed no abnormalities. Optical coherence tomography
      (OCT) demonstrated bilateral temporal inner retinal hyperreflectivity, and
      multifocal electroretinography (mfERG) confirmed retinal dysfunction. Several
      weeks later, ophthalmoscopy and angiography demonstrated macular arteriolar
      occlusive disease. CONCLUSIONS: Simultaneous bilateral macular occlusive events
      are uncommon in patients particularly with SC disease. Although the binasal field
      defects raised the suspicion of a process affecting the optic nerves, the OCT and
      mfERG proved essential in diagnosing retinal rather than optic nerve disease.

PMID- 17452186
TI  - Diagnostic ability of optical coherence tomography with a normative database to
      detect band atrophy of the optic nerve.
AB  - PURPOSE: To evaluate the diagnostic ability of stratus optical coherence
      tomography (OCT) with a normative database to detect band atrophy (BA) of the
      optic nerve. DESIGN: Cross-sectional study. METHODS: StratusOCT retinal nerve
      fiber layer thickness scans were obtained in 37 eyes with BA and permanent
      temporal visual field defect and 37 healthy eyes. The categorization of eyes
      according to the normative database of the instrument and sensitivity and
      specificity values were reported. RESULTS: The average thickness parameter
      demonstrated the highest sensitivity for detection of abnormalities in eyes with
      BA, followed by the parameters related to the temporal and nasal quadrants.
      Values of sensitivity were relatively lower for the 30 degree segments.
      CONCLUSION: StratusOCT with a normative database performed well in detecting
      retinal nerve fiber layer (RNFL) loss in eyes with BA. Clinicians should be aware
      of possible detection failure in the 30 degree segmental analysis, particularly
      at the 3 o'clock meridian.

PMID- 17452187
TI  - Rubella virus-associated uveitis in a nonvaccinated child.
AB  - PURPOSE: To report presumed Fuchs heterochromic uveitis (FHU) associated with
      Rubella virus (RV)-specific intraocular antibody production in a child who was
      not vaccinated against rubella. DESIGN: Observational case report. METHODS: We
      examined a 13-year-old boy with chronic anterior uveitis complicated by mature
      cataract. Two aqueous humor (AH) samples taken with an interval of four weeks
      were analyzed for intraocular antibody production against RV by calculation of
      the Goldmann-Witmer coefficient. RESULTS: The patient showed all the clinical
      signs for FHU: iris atrophy, stellate keratic precipitates, and cataract.
      Analysis of the AH demonstrated intraocular antibody production against RV in two
      sequential samples. CONCLUSIONS: The data show that RV-associated uveitis can
      already present during childhood. Moreover, this finding suggests that
      nonvaccinated children may be at risk to develop uveitis after RV infection.

PMID- 17452188
TI  - Choroidal folds in Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: To analyze choroidal folds in Vogt-Koyanagi-Harada (VKH) disease by
      fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical
      coherence tomography (OCT). DESIGN: Retrospective, consecutive case series.
      METHODS: Records of 95 patients diagnosed with VKH disease from October 2001 to
      July 2006 were reviewed. All patients underwent FA, 17 patients underwent ICGA,
      and 20 underwent OCT. RESULTS: Of the 95 patients, 11 (12.0%) had choroidal folds
      and showed 10 to 15 hypofluorescent bands radiating from the optic disk that were
      similar to the large retinal vessels in shape and number on FA. On ICGA, the
      choroidal folds showed hyperfluorescence at the late stage. OCT showed clear
      folds but the number of folds was larger than on FA and ICGA. CONCLUSIONS:
      Choroidal folds are not uncommon in VKH disease. FA, ICGA, and OCT can help to
      identify their pathogenesis.

PMID- 17452189
TI  - Primary implant placement with evisceration in patients with endophthalmitis.
AB  - PURPOSE: We report the results of 25 patients with endophthalmitis treated with
      evisceration with and without cornea preservation and primary orbital implants.
      DESIGN: Retrospective observational case series. METHODS: The records of 25
      consecutive patients who underwent evisceration for endophthalmitis between June
      1999 and November 2005 were reviewed. Ages ranged between three and 90 years
      (mean 57.6 years). The cause of endophthalmitis and bacterial agents were
      documented. All the patients were treated with topical, intravitreal, and
      intravenous antibiotics for endophthalmitis before evisceration. RESULTS: The
      follow-up period was between two months and 79 months (mean 25.4 months). All
      patients had relief from their pain and were satisfied with their cosmetic
      appearance and motility. Implant exposure was noted in three (12%) patients and
      pyogenic granuloma in one (4%) patient, which were treated successfully. Eighteen
      of the patients had prosthesis fitting at least eight weeks after operation.
      Seven patients elected to not have prosthesis. CONCLUSION: Unless the
      endophthalmitis is secondary to severe devastating trauma in which there is no
      sclera left, primary orbital implant placement with evisceration in these
      patients is an acceptable treatment.

PMID- 17452190
TI  - Hemangiopericytoma of the optic nerve sheath.
AB  - PURPOSE: To report the clinicopathologic findings in patient with optic nerve
      sheath hemangiopericytoma. DESIGN: Clinicopathologic report. METHODS: The
      clinical, histologic, and immunohistochemical findings of a patient with optic
      nerve sheath hemangiopericytoma were reviewed. RESULTS: An excisional biopsy of
      an optic nerve sheath tumor from a 35-year-old woman showed a staghorn vascular
      pattern consisting of CD34-positive tumor cells. CONCLUSIONS: Hemangiopericytoma
      may occur rarely in the optic nerve sheath.

PMID- 17452191
TI  - Comparison of orbital magnetic resonance imaging in duane syndrome and abducens
      palsy.

PMID- 17452193
TI  - Pediatric ophthalmic computed tomographic scanning and associated cancer risk.

PMID- 17452196
TI  - Microbial keratitis following corneal transplantation.

PMID- 17452206
TI  - Selection bias and vitamin E status in cystic fibrosis.

PMID- 17452208
TI  - New rotavirus vaccines: renewed optimism and reason for caution.

PMID- 17452210
TI  - Leadership in academic general pediatrics.

PMID- 17452211
TI  - Serologic testing for celiac disease: primum non nocere!

PMID- 17452212
TI  - Choosing the right fluid and electrolytes prescription in diabetic ketoacidosis.

PMID- 17452213
TI  - Muscle memory.

PMID- 17452214
TI  - Omega-3 long-chain polyunsaturated fatty acids in older children.

PMID- 17452215
TI  - Childhood onset bipolar disorder: a role for early recognition and treatment.

PMID- 17452216
TI  - Impact of celiac autoimmunity on children with type 1 diabetes.
AB  - OBJECTIVE: Children with type 1 diabetes (T1DM) are at increased risk for celiac
      disease (CD); however, the benefits of screening for IgA tissue transglutaminase
      autoantibodies (TG), a marker for CD, are unclear. STUDY DESIGN: We compared 71
      screening-identified TG+ with 63 matched TG- children with TIDM. Growth, bone
      density, and diabetes control measures were obtained. RESULTS: The group was 10
      +/- 3 years of age, 46% male, with TIDM for 4 +/- 3 years. Z scores for weight
      (0.3 +/- 1 vs 0.7 +/- 0.8, P = .024), body mass index (BMI) (0.3 +/- 0.9 vs 0.8
      +/- -0.8, P = .005), and midarm circumference (0.3 +/- 1.1 vs 0.6 +/- 0.9, P =
      .031) were lower in the TG+ group. Bone mineral density and diabetes control
      measures were similar. When limiting the analysis to the 35 TG+ subjects with
      biopsy changes of CD, the BMI Z score was lower than the control group (0.4 +/-
      0.9 vs 0.7 +/- 0.7, P = .05). CONCLUSIONS: In children with TIDM, screening
      identified evidence of CD is associated with altered body composition, but not
      bone mineral density or diabetes control. Further study is needed to determine
      the benefit of early diagnosis and treatment of CD in TIDM children.

PMID- 17452217
TI  - Preventing a drop in effective plasma osmolality to minimize the likelihood of
      cerebral edema during treatment of children with diabetic ketoacidosis.
AB  - OBJECTIVES: To test whether a drop in effective plasma osmolality (P(Eff osm); 2
      x plasma sodium [P(Na)] + plasma glucose concentrations) during therapy for
      diabetic ketoacidosis (DKA) is associated with an increased risk of cerebral
      edema (CE), and whether the development of hypernatremia to prevent a drop in the
      P(Eff osm) is dangerous. STUDY DESIGN: This study is a retrospective comparison
      of a CE group (n = 12) and non-CE groups with hypernatremia (n = 44) and without
      hypernatremia (n = 13). RESULTS: The development of CE (at 6.8 +/- 1.5 hours) was
      associated with a drop in P(Eff osm) from 304 +/- 5 to 290 +/- 5 mOsm/kg (P <
      .001). Control patients did not show this drop in P(Eff osm) at 4 hours (1 +/- 2
      and 2 +/- 2 vs -9 +/- 2 mOsm/kg; P < .01), because of a larger rise in P(Na)
      and/or a smaller drop in plasma glucose. During this period, the CE group
      received more near-isotonic fluids (69 +/- 9 vs 35 +/- 2 and 27 +/- 3 mL/kg; P <
      .001). The CE group had a higher mortality (3/12 vs 0/57; P = .003), and more
      neurologic sequelae (5/12 vs 1/57; P < .001). CONCLUSIONS: CE during therapy for
      DKA was associated with a drop in P(Eff osm). An adequate rise in P(Na) may be
      needed to prevent this drop in P(Eff osm).

PMID- 17452219
TI  - Delayed developmental language milestones in children with Duchenne's muscular
      dystrophy.
AB  - OBJECTIVES: To document the attainment of developmental milestones in children
      with Duchenne's muscular dystrophy (DMD) and to determine whether early delays
      are associated with later performance on measures of cognition. STUDY DESIGN:
      Retrospective parental report was utilized to document the acquisition of 10
      common developmental milestones in children with DMD (n = 130) and their
      unaffected siblings (n = 59). Children completed tests of cognitive functioning.
      RESULTS: Parents rated children with DMD as delayed on achieving both language
      and motor milestones more frequently than their unaffected siblings. Furthermore,
      those children with DMD who were rated as late talkers or late walkers performed
      more poorly on tests of cognitive function than their on-time peers. CONCLUSIONS:
      In addition to the commonly reported delays in motor milestones, the current
      study documents delays in the acquisition of language milestones as well. These
      early delays are associated with significant impairments in later cognitive
      functioning.

PMID- 17452220
TI  - Effect of fish oil supplementation on fatty acid status, coordination, and fine
      motor skills in children with phenylketonuria.
AB  - OBJECTIVE: To investigate effects of long-chain omega-3 polyunsaturated fatty
      acids (LC-PUFA) on motor skills in patients with phenylketonuria (PKU). STUDY
      DESIGN: Thirty-six patients with PKU (1-11 years of age, good metabolic control:
      plasma phenylalanine < or = 360 micromol/L for > or = 6 months). We determined
      plasma phospholipid fatty acids, and in patients > 4 years of age (N = 24) the
      motometric Rostock-Oseretzky Scale (ROS), before and after supplementation with
      fish oil for 3 months (15 mg docosahexaenoic acid [DHA]/kg body weight daily).
      ROS was also assessed in 22 age-matched controls. RESULTS: Patients had low n-3
      LC-PUFA in plasma phospholipids (DHA, 2.37 +/- 0.10%; eicosapentaenoic acid
      [EPA], 0.4 +/- 0.03%) and poorer ROS performance than controls (motor development
      index [MQ] 107 +/- 3 vs 117 +/- 3, P = .010). Supplementation increased
      phospholipid n-3 LC-PUFA (DHA 7.05 +/- 0.24%; EPA 3.31 +/- 0.19%; P < .001),
      decreased n-6 LC-PUFA (arachidonic acid, 9.26 +/- 0.23% vs 6.76 +/- 0.16%; P <
      .001) and improved ROS (MQ 115 +/- 3.54, P = .011, paired t test). ROS was
      unchanged in 11 retested controls (MQ 115 +/- 5.16, P = NS, paired t test
      multivariate analysis of variance [MANOVA] for time by group, P = .027). Patients
      tolerated fish oil well. Plasma phenylalanine remained unchanged. CONCLUSION: In
      patients with PKU, fish oil supplementation enhances n-3 LC-PUFA levels and
      improves motor skills.

PMID- 17452221
TI  - The poor prognosis of childhood-onset bipolar disorder.
AB  - OBJECTIVE: We examined age of onset of bipolar disorder as a potential course-of
      illness modifier with the hypothesis that early onset will engender more severe
      illness. STUDY DESIGN: A total of 480 carefully diagnosed adult outpatients with
      bipolar disorder (mean age, 42.5 +/- 11.6 years) were retrospectively rated for
      age of illness onset, time to first pharmacotherapy, and course of illness.
      Clinicians prospectively rated daily mood fluctuations over 1 year. RESULTS: Of
      the 480 patients, 14% experienced onset in childhood (12 years or younger); 36%
      in adolescence (13 to 18 years); 32% in early adulthood (19 to 29 years); and 19%
      in late adulthood (after 30 years). Childhood-onset bipolar illness was
      associated with long delays to first treatment, averaging more than 16 years. The
      patients with childhood or adolescent onset reported more episodes, more
      comorbidities, and rapid cycling retrospectively; prospectively, they
      demonstrated more severe mania, depression, and fewer days well. CONCLUSIONS:
      This study demonstrates that childhood onset of bipolar disorder is common and is
      associated with long delays to first treatment. Physicians and clinicians should
      be alert to a possible bipolar diagnosis in children in hopes of shortening the
      time to initiating treatment and perhaps ameliorating the otherwise adverse
      course of illness.

PMID- 17452222
TI  - White coat hypertension in childhood: evidence for end-organ effect.
AB  - OBJECTIVE: To evaluate the hypothesis that white coat hypertension (WCH)
      represents a prehypertensive state by correlating ambulatory blood pressure
      monitoring (ABPM) results with BP response to treadmill exercise (TE) and
      echocardiographic measurement of left ventricular mass index (LVMI) in children
      with high blood pressure (HBP). STUDY DESIGN: We evaluated 119 consecutive
      children age 6 to 18 years (mean = 13.3 years; 65% male) referred for HBP. Office
      systolic BP (SBP) exceeded the 95th percentile for age/sex/height in all of the
      children; 10% also had elevated diastolic BP (DBP). WCH was defined as elevated
      office SBP +/- elevated DBP with normal mean awake ABPM-SBP. ABPM classified 62
      subjects as having WCH and 57 as having HBP. RESULTS: Office BP did not differ
      between the 2 groups. As defined, awake ABPM-SBP was lower in the WCH group
      (males: HBP, 142 +/- 12 vs WCH, 124 +/- 5; females: HBP, 137 +/- 8 vs WCH, 121 +/
      5). Awake and asleep DBP and asleep SBP were significantly lower in the WCH
      group. On TE, maximal SBP exceeded norms for age/sex/body surface area in 63% of
      the HBP group and 38% of the WCH group. LVMI exceeded the 95th percentile for
      age/sex in 59% of the males and 90% of the females in the HBP group and in 33% of
      the males and 36% of the females in the WCH group. CONCLUSIONS: Exaggerated
      exercise BP and/or increased LVMI in 62% of those subjects with WCH suggest that
      this diagnosis in children may represent a prehypertensive state.

PMID- 17452224
TI  - Longitudinal relationship of parental hypertension with body mass index, blood
      pressure, and cardiovascular reactivity in children.
AB  - OBJECTIVE: To investigate whether parental hypertension (HTN) affects children's
      body mass index (BMI) and cardiovascular reactivity (CVR) over time. STUDY
      DESIGN: A longitudinal study of 315 students (black: 23 females, 19 males; white:
      142 females, 131 males) was conducted in the public schools of Obion County,
      Tennessee, between 1987 and 1992. BMI and BMI z scores were calculated. The CVR
      task was a series of video games (taking approximately 10 minutes to play) given
      to the same students in their third-, fourth-, fifth-, seventh-, and eighth-grade
      years. CVR was defined as the change in blood pressure (delta_BP) or heart rate
      (delta_HR) between before playing and while playing the video game. Positive
      parental history of HTN (27.6%) was defined as at least 1 parent with HTN.
      Multivariable regression analyses were performed to estimate the effects of
      parental HTN on children's BMI and CVR over time. RESULTS: Children with parental
      HTN had significant higher BMI, BMI z score, and R_BP than did children without
      parental HTN (BMI: 21.6 vs 19.9, P = .001; BMI z score: 1.6 vs 1.1, P = .003;
      R_SBP: 112.6 vs 110.4 mm Hg, P = .01; R_DBP 62.7 vs 60.6 mm Hg, P = .003) after
      adjustment for covariates. Increased CVR was observed in children with parental
      HTN compared with children without parental HTN but was statistically significant
      only for SBP (delta_SBP: 17.2 vs 14.9 mm Hg; P = .01) after adjustment for
      covariates. CONCLUSIONS: Parental HTN independently predicted children's BMI, BMI
      z score, resting BP, and BP reactivity.

PMID- 17452225
TI  - Diastolic filling abnormalities in children with essential hypertension.
AB  - OBJECTIVE: To evaluate whether essential hypertension impacts diastolic function
      in children. STUDY DESIGN: In this cross-sectional study, patients with essential
      hypertension (n = 50) were compared with a normotensive group (n = 53).
      Echocardiographic assessment of diastolic function included measures derived from
      transmitral, color M-mode, and tissue Doppler interrogation. Cardiac dimensions,
      wall thickness, geometry, and systolic function were also assessed. Multiple
      linear regression analysis was performed to identify predictors of altered
      diastolic function. RESULTS: Diastolic filling abnormalities were found in 36% of
      the children with blood pressure elevation. Those subjects with concentric
      hypertrophy were more significantly affected. Abnormalities in indices reflective
      of left ventricular (LV) relaxation occurred more commonly (39%) than those of LV
      compliance (33%). Elevated indexed LV mass was found to be the most significant
      independent predictor of diastolic filling abnormalities. CONCLUSIONS: LV
      diastolic filling abnormalities were found in one-third of the pediatric subjects
      with essential hypertension. Whether these changes represent an adaptive or
      maladaptive response requires further study.

PMID- 17452226
TI  - Validity, reliability, and responsiveness of a new measure of health-related
      quality of life in children with immune thrombocytopenic purpura: the Kids' ITP
      Tools.
AB  - OBJECTIVE: To refine the disease-specific health-related quality of life measure
      in immune (idiopathic) thrombocytopenic purpura (ITP) and to determine its
      validity, reliability, and responsiveness to change. STUDY DESIGN: The initial
      phase involved cognitive debriefing of 12 families, on the basis of which the
      measure was modified and then named Kids' ITP Tools (KIT). The measure was
      administered on 2 occasions with the Pediatric Quality of Life Inventory (PedsQL)
      to 41 patients with acute ITP and 49 patients with chronic ITP, 2 to 18 years
      old, and their parents (proxy-respondents) at 6 North American centers. RESULTS:
      Patients with acute ITP had lower scores when compared with patients with chronic
      ITP (child 64 versus 76, proxy 69 versus 77). The KIT moderately correlated with
      the PedsQL. Child versus proxy KIT scores showed moderate correlation, and the
      KIT was superior to the PedsQL. Test-retest reliability was substantial in the
      child report, but only moderate for the proxy report, similar to the PedsQL. The
      KIT showed a mean score change of 13 in the child and 15 in the proxy, which was
      greater than the PedsQL child's change of 7 and proxy change of 5. CONCLUSION:
      The KIT is valid, with good distinction between acute and chronic ITP and a
      moderate correlation with the PedsQL. The KIT demonstrated reliability comparable
      with that of the PedsQL, yet it was more responsive to change. Therefore the KIT
      can be used as an outcome measure in future clinical trials of childhood ITP.

PMID- 17452227
TI  - Case control study of psychosocial morbidity in beta thalassemia major.
AB  - OBJECTIVES: To assess the prevalence and the spectrum of psychosocial morbidity
      and its correlation with various social and disease-related factors in children
      with beta thalassemia major. STUDY DESIGN: Sixty children with transfusion
      dependent beta thalassemia major were included in the study group who fulfilled
      these inclusion criteria: 1) age 5 to 15 years; 2) both parents alive and living
      together; 3) negative for human immunodeficiency virus; and 4) no family history
      of any chronic illness or psychological illness. The control group consisted of
      60 children of matched age group and social background. A semi-structured
      interview and 2 preformed questionnaires (Pediatric Symptom Checklist [PSC] and
      Childhood Psychopathology Measurement Schedule [CPMS]) were used to assess
      psychosocial morbidity. RESULTS: The mean score of the PSC was 11.63 +/- 3.79
      (range, 7-24) in children with thalassemia, compared with 5.78 +/- 2.572 (range,
      2-13) in the control group (P < .001). The mean score of the CPMS was 11.63 +/-
      3.6 (range, 6-25) compared with 6.08 +/- 2.8 (range, 1-14) in the study and the
      control group, respectively (P < .001). Among the children with thalassemia, 54%
      had a mean CPMS score > or = 10 (which is considered significant for
      psychopathological disorders), compared with 8.3% in the control group (P <
      .001). CONCLUSION: Children with thalassemia have significantly higher
      psychosocial morbidity. Psychosocial aspects need to be addressed in the overall
      treatment of children with thalassemia to prevent the development of clinically
      manifest psychological disease.

PMID- 17452229
TI  - Nasal intermittent mandatory ventilation versus nasal continuous positive airway
      pressure for respiratory distress syndrome: a randomized, controlled, prospective
      study.
AB  - OBJECTIVE: To evaluate whether nasal intermittent mandatory ventilation (NIMV)
      compared with nasal continuous positive airway pressure (NCPAP) would decrease
      the requirement for endotracheal ventilation in the treatment of respiratory
      distress syndrome (RDS) in preterm infants <35 weeks. STUDY DESIGN: Randomized,
      controlled, prospective, single-center study. Forty-one infants were randomized
      to NCPAP and 43 comparable infants to NIMV (birth weight 1533 +/- 603 vs 1616 +/-
      494 g, gestational age 30.6 +/- 3.0 vs 31.1 +/- 2.3 weeks, P = .5, respectively).
      RESULTS: Infants treated with NIMV and with NCPAP had comparable cardio
      respiratory status at study entry. In the total cohort, infants treated initially
      with NIMV needed less endotracheal ventilation than infants treated with NCPAP
      (25% vs 49%, P < .05) with a similar trend in infants <1500 g; 31% vs 62%, P =.
      06). When controlling for weight and gestational age, NIMV was more successful in
      preventing endotracheal ventilation (P < .05). Infants treated with NIMV had a
      decreased incidence of bronchopulmonary dysplasia (BPD) compared with those
      treated with NCPAP (2% vs 17%, P <. 05, in the total cohort and 5% vs 33%, P <.
      05, for infants <1500 g). CONCLUSIONS: NIMV compared with NCPAP decreased the
      requirement for endotracheal ventilation in premature infants with RDS. This was
      associated with a decreased incidence of BPD.

PMID- 17452230
TI  - Low cortical bone density measured by computed tomography in children and
      adolescents with untreated hyperthyroidism.
AB  - OBJECTIVE: To determine whether increased thyroid hormones levels have an effect
      on various bone components (cortical vs cancellous bone). STUDY DESIGN: The
      anthropometric and 3-dimensional quantitative computed tomography (CT) bone
      measurements, including bone density (BD), cross-sectional area (CSA) of the
      lumbar spine and femur, and cortical bone area (CBA) of the femur, of 18 children
      and adolescents with untreated hyperthyroidism were reviewed and compared with
      those of age-, sex-, and ethnicity-matched historical controls. RESULTS: No
      significant differences in height, weight, body mass index (BMI), or pubertal
      staging between patients and controls were found. Cortical BD was significantly
      lower (P < .001) in children and adolescents with hyperthyroidism compared with
      historical controls. After adjusting for weight and height, no difference in
      femur CSA between hyperthyroid children and historical controls was evident. No
      significant correlations among thyroid hormone levels, antithyroid antibody
      levels, and cortical BD values were found. CONCLUSIONS: As determined by CT,
      cortical bone is the preferential site of bone loss in children and adolescents
      with untreated hyperthyroidism.

PMID- 17452231
TI  - Mitochondrial DNA depletion is a prevalent cause of multiple respiratory chain
      deficiency in childhood.
AB  - OBJECTIVE: To determine the actual incidence of mitochondrial DNA (mtDNA)
      depletion syndrome in multiple respiratory chain deficiency. STUDY DESIGN: We
      carried out a real-time polymerase chain reaction quantification of mtDNA in
      liver or muscle tissue of 100 children with unexplained multiple oxidative
      phosphorylation enzyme deficiency. RESULTS: A reduction of mtDNA copy number to
      <35% of control values was found in liver and/or muscle in half of the children
      (50/100). Most of these patients (32/50; 64%) presented with severe neonatal
      onset liver involvement; 7 (14%) had Alpers syndrome, and 11 (22%) exhibited
      various forms of neurologic involvement. Deoxyguanosine kinase or polymerase
      gamma (POLG) mutations could be identified in 11 of 32 patients with liver
      involvement, and POLG mutations were consistently found in all 7 patients with
      Alpers syndrome. Homozygous thymidine kinase 2 and MPV17 gene mutations were
      found in 2 patients. CONCLUSIONS: Our findings show that mtDNA depletion is a
      prevalent cause of multiple respiratory chain deficiency in infancy.

PMID- 17452232
TI  - Truncal distribution of fat mass, metabolic profile and hypothalamic-pituitary
      adrenal axis activity in prepubertal obese children.
AB  - OBJECTIVE: To investigate whether truncal distribution of fat mass (TDFM) is
      associated with variations of the hypothalamic-pituitary-adrenocortical (HPA)
      axis activity in prepubertal obese children. STUDY DESIGN: TDFM, assessed with
      dual energy X-ray absorptiometry and a comprehensive set of measures of HPA axis
      activity and reactivity have been studied in 45 prepubertal obese children aged 6
      to 11 years (girls) and 6 to 13 years (boys). RESULTS: After adjustment for whole
      body fat mass (%) (WBFM), TDFM correlated positively with insulin (r = 0.50, 95%
      CI [0.23; 0.70]) and homeostasis model assessment of insulin resistance (r =
      0.52, 95% CI [0.25; 0.71]). When adjusted for WBFM, TDFM correlated positively
      with morning plasma cortisol (r = 0.38, 95% CI [0.15; 0.64]) in the total
      population. TDFM correlated negatively with the rise of salivary cortisol after a
      standard meal (r = -0.43, 95% CI [-0.71; -0.02]), obviously in girls. When
      adjusted for WBFM and TDFM, morning plasma cortisol correlated positively with
      total cholesterol (r = 0.41, 95% CI [0.11; 0.65]) and triglyceride (r = 0.44, 95%
      CI [0.14; 0.67]). The rise of salivary cortisol after a standard meal was
      negatively (r = -0.56, 95% CI [-0.85; -0.01]) and positively (r = 0.74, 95% CI
      [0.16; 0.94]) correlated with homeostasis model assessment of insulin resistance
      in boys and girls, respectively. CONCLUSIONS: Association exists in prepubertal
      obese children between TDFM and markers of HPA axis activity. These data suggest
      that HPA axis could be involved early in life in obesity associated with
      pejorative metabolic profile.

PMID- 17452233
TI  - Adenotonsillectomy improves sleep, breathing, and quality of life but not
      behavior.
AB  - OBJECTIVE: To obtain parental perspectives on changes in sleep, breathing,
      quality of life (QOL), and neurobehavioral measures after adenotonsillectomy.
      STUDY DESIGN: This retrospective cohort study comprised otherwise healthy
      children evaluated for obstructive sleep apnea syndrome (OSAS) from 1993 to 2001.
      We compared those children who underwent adenotonsillectomy with those children
      who did not. The parents of 473 children (292 boys) 2 years of age and older were
      sent questionnaires to evaluate QOL and clinical and behavioral changes. For 94
      children 3 years of age and older, behavioral changes were evaluated using the
      Conners' Parent Rating Scale-Revised (CPRS-R) for three different periods: pre
      operatively/pre-polysomnography, postoperatively/postpolysomnography, and
      recently. RESULTS: One hundred and sixty-six questionnaires were returned (35%),
      138 of which were complete with written consent provided. Compared with parents
      of unoperated children, parents of children who had adenotonsillectomy were more
      likely to report improvements in sleep, breathing, and QOL but not improvements
      in concentration, school performance, and intellectual or developmental progress.
      Both short and long term, there were no significant effects of adenotonsillectomy
      on any of the CPRS-R behavior subscales. CONCLUSION: From a parental perspective,
      adenotonsillectomy frequently improves sleep, breathing, and QOL but does not
      often improve neurobehavioral outcomes.

PMID- 17452234
TI  - Pediatricians' practices and attitudes about environmental tobacco smoke and
      parental smoking.
AB  - OBJECTIVE: To assess pediatric resident and preceptor environmental tobacco smoke
      (ETS)-reduction practices and attitudes to inform the development of resident
      tobacco intervention training. STUDY DESIGN: Pediatricians in a teaching hospital
      anonymously completed a 65-item survey. RESULTS: Residents' and preceptors' (n =
      93) ETS actions were generally similar. Pediatricians inconsistently intervened
      across treatment settings and when treating different ETS-related illnesses (eg,
      60% "always" assessed during asthma visits, 13% during otitis visits). Less than
      50% "always" explained ETS risks to smoking parents and less than 33% "always"
      advised about creating smoke-free homes. Most pediatricians reported negative
      attitudes toward smoking parents; however, attitudes were not related to actions.
      Most frequently cited barriers to ETS action were lack of time and low confidence
      in effectiveness. CONCLUSION: Understanding barriers to ETS intervention could
      promote transdisciplinary (TD) training and intervention approaches that
      effectively promote pediatrician advice while offloading the time burden of
      intensive smoking intervention. ETS intervention training should foster
      pediatrician confidence and TD relationships with affiliated health professionals
      who could facilitate intervention, referral, and follow-up necessary to sustain
      smoking behavior change.

PMID- 17452235
TI  - Sulfonylurea-responsive diabetes in childhood.
AB  - We describe a family in which 3/6 siblings had transient, relapsing neonatal
      diabetes. The father and another sibling had diabetes diagnosed at 20 and 9 years
      old, respectively. All affected individuals carried the same KCNJ11 gene
      mutation. In all, sulfonylurea treatment permitted cessation of insulin
      treatment, with improved glycemic control.

PMID- 17452236
TI  - Mutations in bile salt export pump (ABCB11) in two children with progressive
      familial intrahepatic cholestasis and cholangiocarcinoma.
AB  - Fatal peripheral cholangiocarcinoma developed in 2 girls with progressive
      familial intrahepatic cholestasis, ABCB11 mutations, and absent bile salt export
      pump (BSEP) expression. BSEP deficiency may cause cholangiocarcinoma through bile
      composition shifts or bile-acid damage within cells capable of
      hepatocytic/cholangiocytic differentiation. This observation suggests the need
      for hepatobiliary-malignancy surveillance and early consideration for liver
      transplantation.

PMID- 17452238
TI  - Morphea (localized scleroderma).

PMID- 17452239
TI  - Physical activity program for preschool children fails to reduce body mass index.

PMID- 17452240
TI  - Hot air is an effective treatment for head lice.

PMID- 17452241
TI  - Antibiotics are effective in acute otitis media in children younger than 2 years
      with bilateral disease and in children with both otorrhea and acute otitis media.

PMID- 17452242
TI  - Duct tape may not be superior to placebo in the treatment of common warts.

PMID- 17452244
TI  - Rapidly evolving Rab GTPase paralogs and reproductive isolation in Drosophila.
AB  - Alterations at the X-linked Hmr gene of Drosophila melanogaster can fully restore
      viability and partially restore fertility in hybrid flies from crosses between D.
      melanogaster and any of its three most closely related species. Although more
      than one gene is expected to be involved in these barriers to reproduction, a
      single DNA-binding protein was recently identified as HMR. The Hmr gene was shown
      to evolve unusually fast, a feature that supports its role in causing genetic
      incompatibility in a hybrid genotype. The current treatment of hybrid genetics
      focuses not only on Hmr but also on the Rab9D gene, which lies only 1kb from Hmr.
      Rab9D is proposed also to influence hybrid viability. This gene has remained
      tightly linked to Hmr for about 10 million years, but it has diverged even more
      than Hmr with regard to D. melanogaster and its most closely related species.
      Furthermore, the 197-amino acid RAB9D protein contains four amino acid
      substitutions in the D. melanogaster-rescuing mutant Hmr1. Rab9D is shown to have
      evolved under very strong positive selection and to be the most recent member of
      a cluster of six paralogs that encode small RAB GTPases. Four of the six paralogs
      are unique to D. melanogaster in which they have diverged considerably, their
      encoded proteins sharing less than 50% amino acid identities with proteins from
      their orthologs in the closest species. Only two Rab orthologs are present in
      these sibling species and none is present in the genomes of more distantly
      related Drosophila species. Rapidly evolving Rab paralogs near the Hmr locus
      probably developed functional specialization of redundant proteins involved in
      trafficking macromolecules between cytoplasm and nucleus. Positive selection
      acting on duplicates of these Rab genes appears to participate in reproductive
      isolation.

PMID- 17452245
TI  - The Neurospora crassa circadian clock.
AB  - The filamentous fungus Neurospora crassa is one of a handful of model organisms
      that has proven tractable for dissecting the molecular basis of a eukaryotic
      circadian clock. Work on Neurospora and other eukaryotic and prokaryotic
      organisms has revealed that a limited set of clock genes and clock proteins are
      required for generating robust circadian rhythmicity. This molecular clockwork is
      tuned to the daily rhythms in the environment via light- and temperature
      sensitive pathways that adjust its periodicity and phase. The circadian clockwork
      in turn transduces temporal information to a large number of clock-controlled
      genes that ultimately control circadian rhythms in physiology and behavior. In
      summarizing our current understanding of the molecular basis of the Neurospora
      circadian system, this chapter aims to elucidate the basic building blocks of
      model eukaryotic clocks as we understand them today.

PMID- 17452246
TI  - Involvement of homologous recombination in carcinogenesis.
AB  - DNA alterations of every type are associated with the incidence of
      carcinogenesis, often on the genomic scale. Although homologous recombination
      (HR) is an important pathway of DNA repair, evidence is accumulating that
      deleterious genomic rearrangements can result from HR. It therefore follows that
      HR events may play a causative role in carcinogenesis. HR is elevated in response
      to carcinogens. HR may also be increased or decreased when its upstream
      regulation is perturbed or components of the HR machinery itself are not fully
      functional. This chapter summarizes research findings that demonstrate an
      association between HR and carcinogenesis. Increased or decreased frequencies of
      HR have been found in cancer cells and cancer-prone hereditary human disorders
      characterized by mutations in genes playing a role in HR, such as ATM, Tp53,
      BRCA, BLM, and WRN genes. Another evidence linking perturbations in HR and
      carcinogenesis is provided by studies showing that exposure to carcinogens
      results in an increased frequency of HR resulting in DNA deletions in yeast,
      human cells, or mice.

PMID- 17452247
TI  - Mutational analysis of the ribosome.
AB  - The ribosome is responsible for protein synthesis, the translation of the genetic
      code, in all living organisms. Ribosomes are composed of RNA (ribosomal RNA) and
      protein (ribosomal protein). Soluble protein factors bind to the ribosome and
      facilitate different phases of translation. Genetic approaches have proved useful
      for the identification and characterization of the structural and functional
      roles of specific nucleotides in ribosomal RNA and of specific amino acids in
      ribosomal proteins and in ribosomal factors. This chapter summarizes examples of
      mutations identified in ribosomal RNA, ribosomal proteins, and ribosomal factors.

PMID- 17452248
TI  - Application of genomics to molecular breeding of wheat and barley.
AB  - In wheat and barley, several generations of selectable molecular markers have
      been included in the genetic maps; and a large number of qualitative and
      quantitative traits were located in the genomes, some of which are being
      routinely selected in marker-assisted breeding programs. In recent years, a large
      number of expressed sequence tags (ESTs) have been generated for wheat and barley
      that have been used for development of functional molecular markers, preparation
      of transcript maps, and construction of cDNA arrays. These functional genomic
      resources combined together with new approaches such as expression genetics,
      association mapping, allele mining, and informatics (bioinformatic tools) possess
      potential to identify genes responsible for a trait and their deployment in
      practical plant breeding. High costs currently limit the implementation of
      functional genomics in breeding programs. The potential applications together
      with some examples as well as challenges for applying genomics research in
      breeding activities are discussed. Genomics research will continue to enhance the
      efficiency and precision for crop improvement but will not replace conventional
      breeding and evaluation methods.

PMID- 17452249
TI  - Interphase fluorescence in situ hybridization in multiple myeloma and monoclonal
      gammopathy of undetermined significance without and with positive plasma cell
      identification: analysis of 192 cases from the Region of Southern Denmark.
AB  - Interphase fluorescence in-situ hybridization (i-FISH) was used to investigate
      192 patients with multiple myeloma (MM; n = 182) and benign monoclonal gammopathy
      of undetermined significance (MGUS; n = 10). Of the 182 MM cases, 132 were
      investigated without and 50 with positive plasma cell identification (PC-ID+);
      134 were investigated at diagnosis, 32 at time of progression, 7 at time of
      relapse, and 9 were investigated with partial remission or no response. The FISH
      analysis detected 11q23 (n = 61), 13q13 approximately q14 (n = 181), 14q32 (n =
      121), 17p13.1 (n = 181), t(4;14) (n = 76), and t(11;14) (n = 73). Of the 132
      patients investigated without PC-ID+, 61 (46%) showed chromosomal abnormalities,
      compared with 45 of 49 of evaluable cases (92%) with PC-ID+. The increase in
      abnormal cases identified was due mainly to the detection of more cases with 13q
      , 17p-, and der(14)(q32). G-banding cytogenetics was performed in 72 patients;
      abnormalities were revealed in 19 cases (26%). Concordance between G-banding and
      i-FISH for one or more aberrations was found in 14 patients. Translocation
      (11;14) was detected by both methods in four of five cases. In four out of seven
      cases with either near-tetraploidy/triploidy or hypoploidy in the G-banded
      karyotypes, the modal number in the G-banded karyotypes could not be elucidated
      with certainty with i-FISH. Three of the 10 MGUS patients showed abnormalities.
      In conclusion, PC-ID+ is important for the detection of structural aberrations
      and disclosing translocations involving 14q32. Of these, translocations t(4;14)
      constituted 9% and t(11;14), 20%. Finally, based on the small number of
      cytogenetically abnormal cases, it is recommended to include cytogenetics (and,
      for example, the DNA index) in the prognostic armamentarium.

PMID- 17452250
TI  - High-resolution analysis of 3p deletion in neuroblastoma and differential
      methylation of the SEMA3B tumor suppressor gene.
AB  - Large-scale hemizygous loss of chromosome 3p is a common event in neuroblastoma,
      occurring preferentially in tumors that exhibit loss of chromosome 11q and lack
      MYCN amplification. Although numerous tumor suppressor genes (TSG) have been
      mapped to the 3p region, the gene or genes contributing to neuroblastoma
      pathogenesis have remained elusive. High-resolution oligonucleotide array CGH
      mapping of chromosome 3p breakpoints relative to the positions of known TSGs
      indicates that more than one gene may contribute to neuroblastoma pathogenesis.
      We evaluated the methylation status of semaphorin 3B (SEMA3B), one of the
      chromosome 3p TSGs, in neuroblastoma tumors with (n = 12) and without (n = 32) 3p
      deletions. A significantly higher percentage of methylated CpG sites in the
      SEMA3B promoter was detected in tumors exhibiting 3p loss (95%), relative to
      tumors without loss (52%), suggestive of a two-hit mechanism of allele
      inactivation. The involvement of methylation in the control of SEMA3B expression
      was confirmed by treatment of neuroblastoma cell lines with the demethylating
      agent 5-aza-2-deoxycytidine. Transcriptional regulation of this locus is complex,
      however; low levels of SEMA3B expression were also seen in tumors with
      unmethylated SEMA3B promoters (n = 4). SEMA3B is known to play an important role
      in the development of normal sympathetic neurons, and interestingly, we found
      higher levels of SEMA3B expression in differentiated tumors with favorable
      histopathology (n = 19) than in tumors with unfavorable histology (n = 22).
      Furthermore, SEMA3B was upregulated in the SK-N-BE neuroblastoma cell line
      following induction of differentiation with retinoic acid. The association of
      SEMA3B expression with neuroblastoma differentiation suggests that this TSG may
      play a role in neuroblastoma pathobiology.

PMID- 17452251
TI  - Complete cytogenetic and molecular response after imatinib treatment for chronic
      myeloid leukemia in a patient with atypical karyotype and BCR-ABL b2a3
      transcript.
AB  - The molecular hallmark of CML is the BCR-ABL fusion gene, usually with specific
      breakpoints within ABL intron 1 and BCR introns b2, b3, and e19. The
      amplification of the BCR-ABL hybrid gene resulting from additional copies of the
      Ph chromosome has been identified as a mechanism for imatinib (IM) resistance.
      Cytogenetic clonal evolution correlates with the accelerated phase of leukemia,
      whereas deletions in the derivative chromosome 9 are associated with a poor
      prognosis. Relevance in IM therapy is unclear. We report a case of a 39-year-old
      male with chronic phase CML. Cytogenetic studies showed a complex karyotype with
      additional copies of the Ph chromosome, sextasomy 8, and ASS gene deletion. An
      unusual aberrant fusion gene product was derived from the joining of BCR exon 13
      (b2) and ABL exon 3 (a3). During IM treatment, the patient was monitored in 3- to
      6-month intervals. Major cytogenetic response was achieved after 5 months;
      complete cytogenetic and molecular remission was reached after 8 months; after 22
      months, normal karyotype and absence of the BCR-ABL product continued. Our data
      seem to confirm the data of others in regards to the b2a3 breakpoint, suggesting
      a better prognosis, regardless of other unfavorable factors.

PMID- 17452252
TI  - Physical mapping of distinct 7q22 deletions in uterine leiomyoma and analysis of
      a recently annotated 7q22 candidate gene.
AB  - Uterine leiomyoma (UL) is a benign, smooth muscle tumor of the uterus affecting a
      significant proportion of women of reproductive age. Deletions involving
      chromosome 7q22 are common in UL and vary in length. Previously reported 7q22
      deletion intervals were physically mapped using information from the recently
      completed human genome sequence. Four distinct deletion intervals, which included
      a microdeletion reported by our laboratory, were identified. This microdeletion
      contains two known genes, ORC5L and LHFPL3. The single deleted marker in the
      microdeletion was mapped within the LHFPL3 locus. The ORC5L gene has been studied
      in UL. Conversely, LHFPL3 has been annotated only recently, and has therefore not
      been studied in UL. The predicted LHFPL3 protein sequence contained a polyalanine
      domain, and a signature sequence for the PMP22 Claudin protein family. Members of
      this family are transmembrane proteins with roles in differentiation,
      proliferation, and extracellular matrix formation, and have been implicated in
      other tumors. Differences in LHFPL3 expression were observed in both human and
      Eker rat UL. Our results provide evidence for four distinct 7q22 deletion
      intervals, each with multiple candidate genes, including the recently identified
      LHFPL3 gene.

PMID- 17452253
TI  - "Home-brew" FISH assay shows higher efficiency than BCR-ABL dual color, dual
      fusion probe in detecting microdeletions and complex rearrangements associated
      with t(9;22) in chronic myeloid leukemia.
AB  - We carried out fluorescence in situ hybridization (FISH) studies on 18 Ph+
      chronic myeloid leukemia (CML) cases with chromosome 22 genomic deletions with
      the Vysis BCR-ABL dual-color/dual-fusion probe (BCR-ABL DC/DF) to compare the
      hybridization patterns obtained with this approach to those obtained with the
      "home brew" BAC/PAC system. Our results are the following: chromosome 22
      microdeletions less than 400 kilobases (Kb) were not detected by the BCR DC/DF
      probe; FISH analysis with the BCR DC/DF probe in cases bearing chromosome 22
      microdeletions ranging from 400 to 700 Kb produced a faint signal on the der(9);
      and the BCR-ABL DC/DF FISH pattern was comparable to the one obtained by the home
      brew probe in the presence of a 900-Kb chromosome 22 microdeletion. Our home-brew
      FISH system represents an accurate method for revealing a subset of CML patients
      with der(9) microdeletions.

PMID- 17452254
TI  - MLL amplification in acute myeloid leukemia.
AB  - The chromosomal alterations at 11q23 that involve the mixed-lineage leukemia gene
      (MLL, HTRX1, HRX, ALL1) are one of the most common cytogenetic abnormalities in
      acute leukemia and have been associated with a poor prognosis. Given that not all
      MLL alterations are seen under conventional cytogenetics or fluorescence in situ
      hybridization (FISH), it is very important to use molecular techniques to
      determine the cause of alteration. In this study, we describe two cases of AML in
      which FISH analysis showed a high-level 11q23 amplification, to confirm if this
      overexpression may be accompanied by partial tandem duplication of the MLL gene
      (MLL-PTD). Both patients showed complex karyotype and an unfavorable clinical
      course. The 11q23 region characterization included conventional cytogenetics,
      FISH, and comparative genomic hybridization analysis to study the expression
      patterns of several oncogenes located within the amplified region and detection
      of partial tandem duplication of the MLL gene by reverse-transcription polymerase
      chain reaction (RT-PCR) and sequencing. MLL-PTD were detected in the two
      patients. Moreover, patient 1 showed amplification of the MLL flanking region.
      Our data suggest that molecular methods such as RT-PCR or sequencing should be
      used to detect MLL alterations, and that amplification of MLL locus may be
      extended to its flanking region.

PMID- 17452256
TI  - Complex karyotypes confer a poor survival in adult acute myeloid leukemia with
      unfavorable cytogenetic abnormalities.
AB  - Cytogenetics represents the most valuable predictor for a poor outcome in
      patients with acute myeloid leukemia (AML), but it encompasses a heterogeneous
      patient population who might have diverse pathogenesis and clinical courses. In
      particular, the significance of complex chromosome aberrations within this cohort
      has seldom been addressed before. We analyzed 48 AML patients with adverse-risk
      cytogenetics in this study. The complex karyotype (three or more
      numerical/structural cytogenetic changes; 29 patients) was found to occur more
      frequently among the elderly than a noncomplex adverse karyotype (19 patients;
      median age, 71 vs. 48; P = 0.005). The patients' performance status was the sole
      independent factor determining the complete remission rate among patients
      receiving standard induction chemotherapy. On survival analysis, two factors
      independently predicted a longer overall survival: noncomplex karyotypes [vs.
      complex karyotypes, hazard ratio (HR) 0.434, 95% confidence interval (CI) 0.189
      0.994, P = 0.048] and achievement of complete remission [(CR) vs. CR not reached,
      HR 0.170, 95% CI 0.051-0.572, P = 0.004)]. In conclusion, among AML patients with
      adverse cytogenetics, complex chromosomal aberrations occurred more frequently
      among the elderly and predicted a poor outcome. These patients should be
      considered as a unique entity and be separated from those with a noncomplex
      adverse cytogenetic change. Exploring the underlying mechanisms of leukemogenesis
      could improve the therapeutic outcome for this group of patients.

PMID- 17452255
TI  - Isodicentric Philadelphia chromosomes in imatinib mesylate (Gleevec)-resistant
      patients.
AB  - Amplification/duplication of the BCR-ABL gene has been found to be one of the key
      factors leading to drug resistance to imatinib mesylate (IM). In the present
      study, we used G-banding to identify the presence of de novo identical
      isodicentric chromosomes in IM-resistant patients. Fluorescence in situ
      hybridization (FISH) analysis on interphase nuclei confirmed the heterogeneity
      and amplification of the fused BCR-ABL gene. FISH analysis superimposed on G
      banding confirmed the presence of isodicentric Philadelphia chromosomes. The
      impact of the isodicentric Philadelphia chromosomes on genomic instability,
      heterogeneity, and amplification of the Philadelphia chromosomes in IM-resistant
      patients is discussed.

PMID- 17452257
TI  - Trisomy 7 in postoperative spindle cell nodules.
AB  - Postoperative spindle cell nodule is a localized, non-neoplastic, reparative
      lesion composed of closely packed proliferating spindle cells and capillaries
      simulating a leiomyosarcoma. The lesion typically develops at the site of a
      recent surgical wound several weeks to months postoperatively. Local recurrence
      of postoperative spindle cell nodules has not been reported, even after
      incomplete resection. We cytogenetically analyzed two postoperative spindle cell
      nodules, one arising in the vulva and the other in the urinary bladder. Trisomy 7
      was identified as the sole karyotypic abnormality in the lesion from the vulva,
      in which cell culturing and G-banding analysis were possible. The other case,
      from the urinary bladder, showed presence of trisomy 7 by interphase-FISH
      performed on nuclei extracted from paraffin-embedded tissue.

PMID- 17452258
TI  - 13q deletions in B-cell lymphoproliferative disorders: frequent association with
      translocation.
AB  - The 13q14 deletion is the most frequent abnormality in chronic lymphocytic
      leukemias/small lymphocytic lymphomas, and this early rearrangement is observed
      from the start of the disease. The systematic use of a panel of interphase
      fluorescence in situ hybridization (FISH) may not reveal some probes (targeting
      chromosomes 11q, 13q, 17p, and chromosome 12) structural abnormalities. In this
      series, we analyzed metaphases by conventional cytogenetics, followed by
      interphase and metaphase fluorescence in situ hybridization. We were able to
      observe 17 cases of 13q translocations with deletions in eight of them. Three
      distinct regions were involved by translocations in association with or without
      deletions: a region centromeric to RB1 (13q11 approximately 13), a zone telomeric
      to D13D25 (13q21 approximately 31), and a 13q14 region deliniated by RB1 and
      D13S25. In this area, the deletion was variable: RB1 alone (one case), D13S319
      approximately D13S25 (five cases), and from RB1 to D13S25 (two cases). The very
      high frequency of 13q14 loss suggests that these deletions are of pathogenetic
      importance, but, the importance of the translocations remains to be determined.

PMID- 17452259
TI  - Lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia with inv(16)(p13q22) as
      a sole genetic abnormality.
AB  - Inversion of chromosome 16, inv(16)(p13q22), juxtaposes the core binding factor
      beta (CBFB) and myosin heavy chain 11 (MYH11) genes, resulting in a myeloid
      leukemic disease phenotype characterized by increased bone marrow and peripheral
      blood blasts with myelomonocytic antigen expression and an accompanying
      eosinophilia. This cytogenetic abnormality has been reported in a variety of
      other neoplasms, in which it generally occurs as part of a complex karyotype,
      including rare B-lineage non-Hodgkin lymphomas. We report a case of clinically,
      morphologically, and immunologically typical lymphoplasmacytic
      lymphoma/Waldenstrom macroglobulinemia in which a majority of the malignant cells
      had an inv(16)(p13q22) as a sole abnormality. We review the literature and
      discuss the possible role of this genetic lesion in B-cell neoplasia.

PMID- 17452260
TI  - Cryptic ins(4;11)(q21;q23q23) detected by fluorescence in situ hybridization: a
      variant of t(4;11)(q21;q23) in an infant with a precursor B-cell acute
      lymphoblastic leukemia report of a second case.
AB  - We report the chromosomal findings in a 4-year-old female with precursor B-cell
      acute lymphoblastic leukemia (ALL). The diagnostic karyotype showed an
      isochromosome 7q, i(7)(q10), as well as questionable rearrangements on 9p and
      11q. Fluorescence in situ hybridization (FISH) studies on both interphase and
      metaphase cells using the MLL "break-apart" and the centromeric chromosome 4
      probes were instrumental in the characterization of an MLL gene rearrangement,
      which was cryptic by conventional cytogenetic analysis. Specifically, the FISH
      pattern was consistent with an insertion of the 5' region of the MLL gene into
      chromosome 4 at band q21, most likely a variant t(4;11)(q21;q23). This is the
      second case of FISH detection of an ins(4;11) in ALL. Our case exemplifies the
      importance of FISH in the further characterization of precursor B-cell ALL cases
      without any apparent prognostically significant chromosomal abnormalities.

PMID- 17452261
TI  - Chromosomal aberrations in oral solitary fibrous tumor.
AB  - The results of cytogenetic analysis of a solitary fibrous tumor (SFT) of the oral
      cavity in a 43-year-old man is reported. The abnormal cells carried a complex
      translocation with the karyotype 46,XY [15
      cells]/46,XYt(1;17;18)(p13;q11.2;q21)[5 cells]. This is the first case reporting
      chromosomal aberrations in an oral SFT.

PMID- 17452262
TI  - Images in emergency medicine. Adult epiglottitis.

PMID- 17452263
TI  - Update on emerging infections from the Centers for Disease Control and
      Prevention. Revised recommendations for HIV testing of adults, adolescents, and
      pregnant women in health-care settings.

PMID- 17452264
TI  - You shall not stand by.

PMID- 17452265
TI  - Evidence-based emergency medicine/critically appraised topic. The role of
      antibiotic prophylaxis for prevention of infection in patients with simple hand
      lacerations.
AB  - STUDY OBJECTIVE: The use of prophylactic antibiotics in patients with simple hand
      lacerations is controversial. This evidence-based emergency medicine review
      evaluates the existing evidence about the utility of prophylactic systemic
      antibiotics for prevention of infection in patients with simple hand lacerations.
      METHODS: MEDLINE, EMBASE, the Cochrane Library, and other databases were
      searched. Studies were selected for possible inclusion in the review if the
      authors stated that they had randomly assigned patients to an antibiotic
      treatment group or a control group and if they followed them up for the
      occurrence of infection. They also had to describe a reasonable method of wound
      cleaning for all subjects, repair the wounds, and exclude hand lacerations that
      involved special tissues such as bone, tendons, nerves, or large vessels.
      Standard criteria to appraise the quality of published trials were used. RESULTS:
      Four randomized trials met the inclusion criteria, of which 3 met minimally
      acceptable quality standards. Relative risks of infection after antibiotic use
      were 1.05 (95% confidence interval [CI] 0.09 to 11.38), 0.73 (95% CI 0.37 to
      1.46), and 1.07 (95% CI 0.07 to 16.80) for the 3 included studies. In these
      trials, the differences in infection rates between antibiotic and control groups
      failed to reach statistical significance. CONCLUSION: No convincing trend toward
      either benefit or harm from administration of antibiotics for uncomplicated hand
      lacerations is apparent. Clinical judgment based on individual cases should be
      used in such settings.

PMID- 17452266
TI  - Evidence-based emergency medicine/editorial. Evidence, values, communication:
      essential ingredients of shared emergency medicine decisionmaking.

PMID- 17452267
TI  - The Zerhouni challenge: defining the fundamental hypothesis of emergency care
      research.

PMID- 17452268
TI  - Report of the Task Force on Residency Training Information (2006-2007), American
      Board of Emergency Medicine.
AB  - The American Board of Emergency Medicine (ABEM) gathers extensive background
      information on emergency medicine residency training programs and the residents
      training in those programs. We present the tenth annual report on the status of
      US emergency medicine residency programs.

PMID- 17452269
TI  - ED doc or soldier?

PMID- 17452270
TI  - Images in emergency medicine. Deep sulcus sign.

PMID- 17452271
TI  - Non-invasive screening for carbon monoxide toxicity in the emergency department
      is valuable.

PMID- 17452273
TI  - Ultrasonographic guidance for all central venous catheter insertions: a
      "desirable practice alternative," or the new standard of care?

PMID- 17452274
TI  - Inadvertent carotid artery cannulation during ultrasound guided central venous
      catheterization.

PMID- 17452275
TI  - Intranasal fentanyl for acute pain: techniques to enhance efficacy.

PMID- 17452276
TI  - The emergency department is not the ideal place for routine HIV testing.

PMID- 17452277
TI  - Selective triage for victims of sexual assault to designated exam facilities.

PMID- 17452278
TI  - Advocating for Certified Emergency Nurses (CENs) in departments of emergency
      medicine.

PMID- 17452279
TI  - Comments on evolution of sleep and the palliopallial connectivity in mammals and
      birds.
AB  - This commentary is referred to the review signed by Rattemborg [N.C. Rattenborg,
      Evolution of slow wave sleep and palliopallial connectivity in mammals and birds.
      A hypothesis. Brain Res. Bull. 69 (2006) 20-29]. We propose that the review
      missed important aspects in relation to the characteristics of sleep in
      poikilotherm vertebrates and in the evolution of sleep. Poikilotherms
      continuously show an EEG dominated by slow waves, but its highest amplitude
      appears not during sleep, but during active waking. In addition, they show an
      arousal reaction which consists in an increase in EEG amplitude and synchrony,
      opposite to mammals and birds. As a consequence, most of the conclusions proposed
      in the review should be rejected.

PMID- 17452280
TI  - Response to commentary on evolution of slow-wave sleep and palliopallial
      connectivity in mammals and birds: a hypothesis.
AB  - Mammals and birds are the only animals that exhibit high-amplitude slow-waves
      (SWs) in the electroencephalogram during sleep. The SWs that characterize slow
      wave sleep (SWS) in mammals and birds reflect the large-scale synchronization of
      slow neuronal activity. In mammals, this synchronization is dependent upon the
      high degree of interconnectivity within the neocortex, a cytoarchitectonic trait
      also found in the avian hyperpallium, but not the reptilian dorsal cortex.
      Consequently, I recently proposed that the presence of SWs in sleeping mammals
      and birds, and their absence in sleeping reptiles, is attributable to the greater
      degree of interconnectivity within the neocortex and hyperpallium when compared
      to the dorsal cortex [N.C. Rattenborg, Evolution of slow-wave sleep and
      palliopallial connectivity in mammals and birds: A hypothesis, Brain Res. Bull.
      69 (2006) 20-29]. Rial et al. (this issue) challenge this hypothesis by noting
      that high-amplitude SWs occur in awake reptiles. Based largely on this
      observation, they suggest that SWS in homeotherms evolved from reptilian
      wakefulness. SWs in awake reptiles do not seem to reflect neural processes
      comparable to those that generate sleep-related SWs in homeotherms, however.
      Moreover, the proposed conversion of reptilian wakefulness into SWS is untenable
      from behavioral, mechanistic and functional perspectives. A more parsimonious
      explanation is that the precursor state to SWS in homeotherms was a state
      comparable to reptilian sleep, rather than wakefulness, with the primary
      difference being that the reptilian dorsal cortex lacks the interconnectivity
      necessary to generate sleep-related SWs in the electroencephalogram.

PMID- 17452281
TI  - Role of presynaptic nicotinic acetylcholine receptors in the regulation of
      gastrointestinal motility.
AB  - Presynaptic nicotinic acetylcholine receptors (nAChRs) located on cholinergic
      terminals facilitate the release of acetylcholine (ACh), thereby constituting a
      fail-safe mechanism at strategic locations, such as the neuromuscular junction,
      where reliable transmission is vital. Accumulating data indicate that myenteric
      neurons in the enteric nervous system possess not only somatodendritic nAChRs,
      which mediate cholinergic transmission between neurons, but also presynaptic
      nAChRs. Functional evidence shows that these receptors mediate a positive
      feedback with respect to ACh release from myenteric motoneurons, and might
      therefore play an important role in the regulation of gastrointestinal motility.
      These presynaptic nAChRs were found to be more sensitive to nicotinic ligands
      than somatodendritic nAChRs and could therefore be primary targets of exogenous
      compounds, such as nicotine. This interaction might provide a neurochemical basis
      for the effect of smoking on gastrointestinal motility. Another important human
      pharmacological implication is based on our recent observation that monoamine
      uptake inhibitor-type antidepressant drugs are able to inhibit presynaptic nAChRs
      in the enteric nervous system. The disruption of the nAChR-mediated positive
      feedback modulation by antidepressants might explain the frequent occurrence of
      constipation, a common side effect, attributed to these drugs. Clarification of
      the role of presynaptic nAChRs in feedback mechanisms in the enteric nervous
      system might be instrumental in the development of new drugs affecting
      gastrointestinal motility.

PMID- 17452282
TI  - Whither withered Golgi? A retrospective evaluation of reticularist and synaptic
      constructs.
AB  - The 100th anniversary of the shared first Nobel prize in neuroscience by Camillo
      Golgi and Ramon y Cajal invites reappraisal of the merits of the arguments
      adduced by these two combative scientists in the light of contemporary knowledge.
      Guided by cogent reasons for reluctance in accepting the inviolable polarity
      principle of the neuron doctrine and concern for explaining cerebral recovery of
      function, Golgi joined the 'reticularists' of his generation. Modern observations
      of axo-axonic and dendro-dendritic synapses, gap-junction interconnections, rules
      for the direction and mode of analog or impulse conduction, the myriad diversity
      of ion channels and gating principles and the complexities of synaptic plasticity
      have eclipsed the polarized neuron doctrine explanations of reflex physiology and
      the 'fixed and immutable' connections successfully championed by Cajal. Without
      violating the cell theory, expanded modes of neuronal and glial communication
      have encompassed reticularist notions and provided insight into the long-term
      changes underlying synaptic and extra-synaptic neural patterns. Both laureates
      espoused operative principles that have survived in different modes and
      distinctive temporal domains. Together, they reflect the roots of our
      contemporary understanding of neural interaction.

PMID- 17452283
TI  - Safety aspects of transcranial direct current stimulation concerning healthy
      subjects and patients.
AB  - Cortical excitability changes induced by tDCS and revealed by TMS, are
      increasingly being used as an index of neuronal plasticity in the human cortex.
      The aim of this paper is to summarize the partially adverse effects of 567 tDCS
      sessions over motor and non-motor cortical areas (occipital, temporal, parietal)
      from the last 2 years, on work performed in our laboratories. One-hundred and two
      of our subjects who participated in our tDCS studies completed a questionnaire.
      The questionnaire contained rating scales regarding the presence and severity of
      headache, difficulties in concentrating, acute mood changes, visual perceptual
      changes and any discomforting sensation like pain, tingling, itching or burning
      under the electrodes, during and after tDCS. Participants were healthy subjects
      (75.5%), migraine patients (8.8%), post-stroke patients (5.9%) and tinnitus
      patients (9.8%). During tDCS a mild tingling sensation was the most common
      reported adverse effect (70.6%), moderate fatigue was felt by 35.3% of the
      subjects, whereas a light itching sensation under the stimulation electrodes
      occurred in 30.4% of cases. After tDCS headache (11.8%), nausea (2.9%) and
      insomnia (0.98%) were reported, but fairly infrequently. In addition, the
      incidence of the itching sensation (p=0.02) and the intensity of tingling
      sensation (p=0.02) were significantly higher during tDCS in the group of the
      healthy subjects, in comparison to patients; whereas the occurrence of headache
      was significantly higher in the patient group (p=0.03) after the stimulation. Our
      results suggest that tDCS applied to motor and non-motor areas according to the
      present tDCS safety guidelines, is associated with relatively minor adverse
      effects in healthy humans and patients with varying neurological disorders.

PMID- 17452284
TI  - Chronic nicotine administration. Analysis of the development of hypertension and
      glutamatergic neurotransmission.
AB  - Among numerous neurotransmitters involved in central cardiovascular control,
      glutamate is one of the most studied transmitters that are related to nicotine
      considering its release and its postsynaptic regulation. However, there are no
      conclusive studies about nicotine effects on glutamatergic system and its
      relevance on hypertension development, which can help to understand the role of
      these two systems in that pathology. In this context, the objective of the
      present study is to evaluate the effects of systemic chronic nicotine exposure on
      hypertension development as well as the interaction between nicotine and the
      glutamatergic system in normotensive and neurogenic hypertensive rats. By means
      of high performance liquid chromatograph, immunohistochemistry, in situ
      hybridization and binding techniques, glutamatergic system was evaluated in SHR
      and Wistar Kyoto (WKY) rats treated with nicotine, delivered subcutaneously
      through nicotine pellets, for 8 weeks. The most important findings in this study
      were that (1) moderate doses of nicotine accelerated the onset and increased
      blood pressure in SHR but not in WKY rats, (2) the nicotine dosage and time of
      treatment employed did not affect body weight, (3) chronic nicotine treatment
      differentially affected glutamatergic system in normotensive and hypertensive
      rats, and (4) spontaneously hypertensive rats seem to be more sensitive to
      peripherally administered nicotine than Wistar Kyoto rats considering blood
      pressure and glutamatergic neurotransmission changes. In conclusion, we have
      demonstrated that a moderate dose of nicotine accelerates the onset and
      exacerbates hypertension in the SHR and that might be, at least in part, related
      to the modulation of glutamatergic neurotransmission.

PMID- 17452285
TI  - Gene expression profile in beta-amyloid-treated SH-SY5Y neuroblastoma cells.
AB  - The beta-amyloid peptide, the major component of the senile plaques in
      Alzheimer's disease (AD), has been probed to be toxic to neurons both in vivo and
      in vitro. Several mechanisms have been proposed to be involved in the amyloid
      induced neurotoxicity; among others it has been suggested that the beta-amyloid
      peptide exerts its toxic effect mainly by activating the surrounding microglia
      population, which in turn induces the synthesis and release of preapoptotic and
      pro-inflammatory factors. In addition, a direct effect of beta-amyloid on neurons
      has been also described. However, the precise mechanisms involved in the amyloid
      induced neurotoxicity have been not yet definitely clarified. To characterize the
      effects directly induced on neurons, we have analyzed the gene expression profile
      induced by the 25-35 beta-amyloid fragment in human SH-SY5Y neuroblastoma cells,
      by using the Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Our results
      confirm that beta-amyloid may directly induce neuronal cell death; activating
      signals that in vivo have been described as causative of Alzheimer's disease.

PMID- 17452287
TI  - Effects of NMDA receptor antagonist memantine on mismatch negativity.
AB  - Mismatch negativity (MMN) and its magnetic counterpart (MMNm) have been shown to
      be altered in patients with various psychiatric and neurological disorders, e.g.
      Alzheimer's disease and schizophrenia, indicating deficits in involuntary
      attention. N-Methyl-D-aspartate (NMDA) receptor-mediated glutamate dysfunction is
      suggested to underlie these deficits. However, the role of NMDA receptors in
      involuntary attention is poorly understood. Memantine is an NMDA receptor
      antagonist that has been demonstrated to be effective in the treatment of
      patients with Alzheimer's disease. We aimed to investigate whether a single dose
      of memantine would affect MMN/MMNm in healthy subjects studied with simultaneous
      electroencephalography (EEG) and magnetoencephalography (MEG). Monaural left-ear
      auditory stimuli were presented in a passive oddball paradigm with infrequent
      deviant tones differing in frequency and duration. Neuronal activity was recorded
      in 13 healthy subjects after oral administration of 30mg of memantine or placebo
      in a randomized, double-blind, cross-over design. MMNm was analyzed using
      equivalent current dipoles. MMN was evaluated from frontocentral electrodes.
      Memantine lowered subjects' arousal level as measured by visual analog scales,
      and enhanced the amplitude of MMN in EEG. No differences in MMN latency were
      observed in MEG or EEG. Memantine did not affect the location, strength,
      amplitude or latency of MMNm, P1m, and N1m components. No changes in amplitude or
      latency were observed for P1 and N1 peaks. These results indicate that memantine
      affects involuntary attention without otherwise changing auditory processing of
      the stimuli. As memantine-induced changes in MMN were detected only in EEG, we
      suggest that the effect is mostly related to the frontal cortex.

PMID- 17452288
TI  - Brain network for passive word listening as evaluated with ICA and Granger
      causality.
AB  - Brain network modeling is probably the biggest challenge in fMRI data analysis.
      Higher cognitive processes in fact, rely on complex dynamics of temporally and
      spatially segregated brain activities. A number of different techniques, mostly
      derived from paradigmatic hypothesis-driven methods, have been successfully
      applied for such purpose. This paper instead, presents a new data-driven analysis
      approach that applies both independent components analysis (ICA) and the Granger
      causality (GC). The method includes two steps: (1) ICA is used to extract the
      independent functional activities; (2) the GC is applied to the independent
      component (IC) most correlated with the stimuli, to indicate its functional
      relation with other ICs. This new method is applied to the analysis of fMRI study
      of listening to high-frequency trisyllabic words, non-words and reversed words.
      As expected, activity was found in the primary and secondary auditory cortices.
      Additionally, a parieto-frontal network of activations, supported by temporal and
      causality relationships, was found. This network is modulated by experimental
      conditions in agreement with the most recent models presented for word
      perception. The results have confirmed the validity of the proposed method, and
      seem promising for the detection of cognitive causal relationships in
      neuroimaging data.

PMID- 17452286
TI  - Comparative developmental neurotoxicity of organophosphates in vivo:
      transcriptional responses of pathways for brain cell development, cell signaling,
      cytotoxicity and neurotransmitter systems.
AB  - Organophosphates affect mammalian brain development through a variety of
      mechanisms beyond their shared property of cholinesterase inhibition. We used
      microarrays to characterize similarities and differences in transcriptional
      responses to chlorpyrifos and diazinon, assessing defined gene groupings for the
      pathways known to be associated with the mechanisms and/or outcomes of
      chlorpyrifos-induced developmental neurotoxicity. We exposed neonatal rats to
      daily doses of chlorpyrifos (1mg/kg) or diazinon (1 or 2mg/kg) on postnatal days
      1-4 and evaluated gene expression profiles in brainstem and forebrain on day 5;
      these doses produce little or no cholinesterase inhibition. We evaluated pathways
      for general neural cell development, cell signaling, cytotoxicity and
      neurotransmitter systems, and identified significant differences for >60% of 252
      genes. Chlorpyrifos elicited major transcriptional changes in genes involved in
      neural cell growth, development of glia and myelin, transcriptional factors
      involved in neural cell differentiation, cAMP-related cell signaling, apoptosis,
      oxidative stress, excitotoxicity, and development of neurotransmitter synthesis,
      storage and receptors for acetylcholine, serotonin, norepinephrine and dopamine.
      Diazinon had similar effects on many of the same processes but also showed major
      differences from chlorpyrifos. Our results buttress the idea that different
      organophosphates target multiple pathways involved in neural cell development but
      also that they deviate in key aspects that may contribute to disparate
      neurodevelopmental outcomes. Equally important, these pathways are compromised at
      exposures that are unrelated to biologically significant cholinesterase
      inhibition and its associated signs of systemic toxicity. The approach used here
      demonstrates how planned comparisons with microarrays can be used to screen for
      developmental neurotoxicity.

PMID- 17452289
TI  - Effect of basal forebrain neuropeptide Y administration on sleep and spontaneous
      behavior in freely moving rats.
AB  - Neuropeptide Y (NPY) is present both in local neurons as well as in fibers in the
      basal forebrain (BF), an area that plays an important role in the regulation of
      cortical activation. In our previous experiments in anaesthetized rats,
      significant EEG changes were found after NPY injections to BF. EEG delta power
      increased while power in theta, alpha, and beta range decreased. The aim of the
      present experiments was to determine whether NPY infusion to BF can modulate
      sleep and behavior in freely moving rats. In this study, microinjections were
      made into the BF. Saline was injected to the control side, while either saline or
      one of two doses of NPY (0.5 microl, 300-500 pmol) to the treated side. EEG as
      well as behavioral changes were recorded. Behavioral elements after the NPY
      injections changed in a characteristic fashion in time and three consecutive
      phases were defined. In phase I (half hour 2), activated behavioral items
      (moving, rearing, grooming) appeared frequently. In phase II (half hours 3 and 4)
      activity decreased, while motionless state increased. Reappearance of activity
      was seen in phase III (half hours 5 and 6). NPY injections caused sleep-wake
      changes. The three phases described for behavioral changes were also reflected in
      the sleep data. During phase I, lower NPY dose increased wakefulness and
      decreased deep sleep. Reduced behavioral activity seen in phase II was partially
      reflected in the sleep. In this phase, wakefulness tended to increase in the
      third half hour, while decreased in the 4th half hour. Deep sleep and total slow
      wave sleep non-significantly decreased in the third and increased in the 4th half
      hour. In most cases, wakefulness was elevated again during Phase III, while sleep
      decreased. Length of single sleep-wake epochs did not change after NPY
      injections. Our results suggest a role for NPY in the integration of sleep and
      behavioral stages via the BF.

PMID- 17452290
TI  - Protein kinase C-regulated cAMP response element-binding protein phosphorylation
      in cultured rat striatal neurons.
AB  - The transcription factor cAMP response element-binding protein (CREB) promotes
      target DNA transcription in response to cellular stimulation in brain neurons.
      Phosphorylation of CREB is regulated by a variety of extracellular and
      intracellular signals. In this study, protein kinase C (PKC)-regulated CREB
      phosphorylation was investigated in cultured rat striatal neurons. We found that
      PKC activation with phorbol 12-myristate 13-acetate (PMA) produced a rapid and
      transient phosphorylation of CREB. The increase in CREB phosphorylation was dose
      dependent and prevented by the two PKC selective inhibitors (chelerythrine and
      Go6983). Interestingly, the PMA-induced CREB phosphorylation was also blocked by
      a calcium/calmodulin-dependent protein kinase inhibitor KN93 and the two mitogen
      activated protein kinase (MAPK) kinase inhibitors PD98059 and U0126, but not by a
      p38 MAPK inhibitor SB203580. PMA activation of PKC markedly increased
      phosphorylation of MAPK/extracellular signal-regulated kinase 1/2. The protein
      kinase A (PKA) inhibitor H89 at a dose that completely blocked the PKA activator
      (8-br-cAMP)-induced CREB phosphorylation partially blocked the PMA-stimulated
      CREB phosphorylation. Furthermore, blockade of NMDA and AMPA glutamate receptors
      and L-type voltage-operated Ca(2+) channels did not alter the ability of PMA to
      induce CREB phosphorylation. These results demonstrate that PKC is among the
      protein kinases that can positively modulate CREB phosphorylation in striatal
      neurons, and the PKC signals to CREB activation are mediated via signaling
      mechanisms involving multiple downstream protein kinases.

PMID- 17452291
TI  - The effect of sevoflurane on the release of [3H]dopamine from rat brain cortical
      slices.
AB  - Dopamine is a neurotransmitter that exerts major control on important brain
      functions and some lines of studies suggest that dopaminergic neurotransmission
      may be a potential target for volatile anesthetics. In the present study, rat
      brain cortical slices were labeled with [(3)H]dopamine to investigate the effects
      of sevoflurane on the release of this neurotransmitter. [(3)H]dopamine release
      was significantly increased in the presence of sevoflurane (0.46 mM) and this
      effect was independent of extracellular or intracellular calcium. In addition,
      [(3)H]dopamine release evoked by sevoflurane was not affected by TTX (blocker of
      voltage-dependent sodium channels) or reserpine (a blocker of the vesicular
      monoamine transporter). These data suggest that the dopamine release induced by
      sevoflurane is non-vesicular, independent of exocytosis and, would be mediated by
      the dopamine transporter (DAT). GBR12909 and nomifensine, inhibitors of DAT,
      decreased the release of [(3)H]dopamine evoked by sevoflurane. The same effect
      was also observed when the brain cortical slices were incubated at low
      temperature and low extracellular sodium. Ouabain, a Na(+)/K(+) ATPase pump
      inhibitor, which is known to induce dopamine release through reverse transport,
      decreased [(3)H]dopamine release induced by sevoflurane. In conclusion, the
      present study suggests that sevoflurane increases [(3)H]dopamine release in brain
      cortical slices that is mediated by DAT located at the plasma membrane.

PMID- 17452292
TI  - Spared place and object-place learning but limited spatial working memory
      capacity in rats with selective lesions of the dentate gyrus.
AB  - We studied the cognitive performance of rats with colchicine-induced lesions of
      the hippocampal dentate gyrus (DG) on a range of spatial, non-spatial and mixed
      spatial/procedural tasks. Rats were assigned to three experimental groups
      receiving large colchicine lesions (7 microg per hippocampus), small colchicine
      lesions (1.75 microg per hippocampus) or sham lesions. Stereological estimates of
      cell density indicated that the colchicine treatments induced dose-dependent
      damage to the DG, while sparing in large part other hippocampal subfields.
      Remarkably, the behavioural results showed that the colchicine lesions did not
      affect the performance of rats in an object discrimination task, in an object
      place associative task in which a familiar object was displaced from a given
      position nor in a spontaneous spatial discrimination task performed in the T
      maze. However, rats in both lesion groups were severely impaired in a reinforced
      non-matching-to-position working memory task conducted in the T-maze.
      Importantly, performance in the working memory task correlated strongly with cell
      density in the DG but not with cell density in the CA1 and CA3 areas. Only rats
      with large-lesions showed a transient deficit in a reinforced rule-based
      conditional discrimination task. These data demonstrated that rats with selective
      lesions of the DG readily acquire and retain neural representations relative to
      objects and places but are specifically impaired in their ability to update
      rapidly and flexibly spatial information that is essential to guide goal-directed
      actions.

PMID- 17452294
TI  - Increased anxiety and other similarities in temperament of alcoholics with and
      without antisocial personality disorder across three diverse populations.
AB  - According to Cloninger's model, type I alcoholics are thought to be innately
      vulnerable to anxiety and depression. In contrast, type II alcoholics are thought
      to have increased likelihood of antisocial personality disorder (ASPD) and
      reduced anxiety. However, allostatic activations of stress, anxiety, and
      dysphoria may be a common thread in alcohol use disorders (AUDs). Our aim was to
      find commonalities and differences in temperament of alcoholics with and without
      ASPD in three diverse populations. By sib-sib comparisons, we also evaluated the
      extent to which the temperament traits were moderated by familial factors
      including inheritance. We compared harm avoidance (HA), novelty seeking (NS), and
      reward dependence (RD) in alcoholics with ASPD, alcoholics without ASPD, and
      controls. Correlations for each temperament dimension were evaluated in pairs of
      siblings concordant and discordant for AUD. Participants were derived from three
      independent populations: Finnish Caucasians (N=453, men=100%, including a sample
      of alcoholic criminals), a Plains American Indian community sample (N=378;
      men=42%), and a subset of the familial and predominantly Caucasian Collaborative
      Study on the Genetics of Alcoholism (COGA) sample (N=967, men=47%). In all the
      three populations, both alcoholics with and without ASPD were higher in HA than
      controls. The increase of HA among alcoholics as compared to controls ranged from
      54% to 12%. In two populations (COGA and Finns), NS was highest in alcoholics
      with ASPD, intermediate in alcoholics without ASPD, and lowest in controls. HA
      levels were correlated in sib-pairs concordant (either affected or unaffected)
      for AUD but not in discordant pairs. In conclusions, despite cultural diversity
      and different modes of ascertainment we found a consistent pattern of elevated HA
      in all groups of alcoholics, including alcoholics with ASPD. Even in alcoholics
      with long-term exposure to the anxiogenic effects of repeated cycles of alcohol
      withdrawal, genetic and other familial influences seem to play a role in
      moderating anxiety.

PMID- 17452295
TI  - Association of EEG alpha variants and alpha power with alcohol dependence in
      Mexican American young adults.
AB  - Several studies support an association between electroencephalogram (EEG) voltage
      and alcohol dependence. However, the distribution of EEG variants also appears to
      differ depending on an individual's ethnic heritage, suggesting significant
      genetic stratification of this EEG phenotype. The present study's aims were to
      investigate the incidence of EEG alpha variants and spectral power in the alpha
      frequency range in Mexican American young adults based on gender, and personal
      and family history of alcohol dependence. Clinical ratings (high-, medium-, and
      low alpha voltage variants) and spectral characteristics of the EEG in the alpha
      frequency range (7.5-12 Hz) were investigated in young adult (age 18-25 years)
      Mexican American men (n=98) and women (n=138) who were recruited from the
      community. Nineteen percent (n=45) of the participants had a low-voltage alpha
      EEG variant, 18% had a high-voltage variant, and 63% had a medium-voltage
      variant. There were no significant differences in the distribution of the EEG
      variants based on family history of alcohol dependence. There was a significant
      relationship between gender and the three alpha variants (chi2=9.7; df=2;
      P<.008), and there were no male participants with alcohol dependence with high
      alpha variants (chi2=5.8; df=2; P<.056). Alcohol dependence, but not a family
      history of alcohol dependence, was associated with lower spectral power in the
      alpha frequency range in the right (F=4.4; df=1,96; P<.04) and left (F=5.3;
      df=1.96; P<.02) occipital areas in the men but not in the women. In conclusion,
      in this select population of Mexican American young adults, male gender and
      alcohol dependence are associated with an absence of high-voltage alpha variants
      and lower alpha power in the EEG. These data suggest that EEG low voltage, a
      highly heritable trait, may represent an important endophenotype in male Mexican
      Americans that may aid in linking brain function with genetic factors underlying
      alcohol dependence in this ethnic group.

PMID- 17452297
TI  - Cue-induced reinstatement of ethanol seeking in Sardinian alcohol-preferring
      rats.
AB  - The purpose of the present study was to characterize cue-induced reinstatement of
      ethanol seeking in selectively bred Sardinian alcohol-preferring (sP) rats
      trained to lever press for ethanol in 30-min self-administration sessions. Four
      responses on an "active" lever led to presentation of 0.1 ml of 15% (vol/vol)
      ethanol by a liquid dipper and concurrent activation of a set of discrete light
      and auditory cues. In a 70-min extinction/reinstatement session, responding was
      first extinguished for 60 min. Subsequently, different stimuli were delivered in
      a noncontingent manner and reinstatement of nonreinforced responding was
      assessed. Fifteen presentations of the ethanol-predictive stimulus complex,
      including the dipper cup containing 5 or 15% ethanol, potently reinstated
      responding on the previously active lever. The magnitude of reinstatement
      increased with the number of stimulus presentations and concentration of ethanol
      presented by the dipper cup. Fifteen presentations of the ethanol-predictive
      stimulus complex, including the dipper cup filled with water (0% ethanol), did
      not produce any reinstatement. These results indicate that (1) noncontingent
      presentations of the ethanol-predictive stimulus complex may reinstate ethanol
      seeking in sP rats and (2) the orosensory properties of ethanol may play an
      important role in reinstatement of ethanol seeking in sP rats. The latter finding
      concurs with clinical observations that odor and taste of alcoholic beverages
      elicit immediate craving responses in abstinent alcoholics.

PMID- 17452296
TI  - Influence of reinforcement schedule on ethanol consumption patterns in non-food
      restricted male C57BL/6J mice.
AB  - Ethanol reinforcement should ideally be evaluated in animals that are not food
      deprived to ensure that the motivation behind its consumption is pharmacological,
      and not caloric, in nature. The objective of this work was to assess the
      influence of reinforcement schedule on ethanol intake in nondeprived mice. Male
      C57BL/6J mice were trained to respond on an ethanol-reinforced lever on a fixed
      ratio 4 reinforcement schedule for 10% ethanol (10E). The appetitive and
      consummatory phases were then procedurally separated by changing the response
      requirement (RR), so that mice were permitted 30-min continuous 10E access after
      completion of either four (RR4) or eight (RR8) responses. Phase separation
      yielded a heightened appetitive drive to acquire 10E access (as indexed by a
      significant decrease in the latency to first active lever and a trend toward a
      decrease in the latency to first sipper contact) and an augmented level of
      drinking (twofold elevation in the ethanol dose consumed). Robust extinction
      responding on the ethanol-appropriate lever indicated that ethanol was effective
      as a behavioral reinforcer. These results suggest that the separation of
      appetitive and consummatory phases of ethanol self-administration may prove
      useful in future evaluations of the pharmacological and genetic bases of ethanol
      reinforcement in mice.

PMID- 17452298
TI  - Differential motivational properties of ethanol during early ontogeny as a
      function of dose and postadministration time.
AB  - While appetitive reinforcement effects of ethanol are easily detected in rat
      neonates, such phenomena rarely have been observed in older infants. Recently,
      Molina et al. [Molina, J. C., Ponce L. F., Truxell, E., & Spear N. E. (2006).
      Infantile sensitivity to ethanol's motivational effects: ethanol reinforcement
      during the third postnatal week. Alcohol Clin Exp Res 30, 1506-1519] reported
      such effects of ethanol in 14-day-olds using a second-order conditioning
      procedure. Infants also appear to be sensitive to biphasic reinforcement or
      general motivational effects of ethanol, with appetitive effects seeming to occur
      early in the state of intoxication and aversive effects predominant during late
      stages, but tests have been inconclusive. The present study examined the
      possibility of biphasic motivational effects of ethanol during infancy through
      the use of second-order conditioning procedures. Preweanling rats (14 days old)
      experienced intraoral water infusions (conditioned stimulus, CS) either 5-20 or
      30-45 min after administration of 0.5 or 2.0 g/kg i.g. ethanol. Pups were then
      exposed to the CS while over a novel texture (second-order phase). Tests of
      tactile preference for that texture followed. Locomotive, thermal, hormonal
      (corticosterone release), and pharmacokinetic patterns likely to underlie the
      acquisition of ethanol-mediated conditioning were also examined in subsequent
      experiments. Intraoral CSs paired with either early or late effects of low-dose
      ethanol (0.5 g/kg, blood ethanol concentration: 40 mg%) became positive second
      order reinforcers. Appetitive effects were also exhibited by pups exposed to the
      CS during commencement of the toxic episode induced by a 2.0 g/kg ethanol dose, 5
      20 min after administration of ethanol, whereas aversions emerged when CS
      presentation occurred 30-45 min postadministration time (blood ethanol
      concentrations: 157 and 200 mg%, respectively). Overall, the results indicate
      that infants rapidly detect differential motivational properties of ethanol as a
      function of dose or drug postadministration time. Relatively neutral stimuli
      associated with these properties are later capable of acting as either positive
      or aversive reinforcers. Thermal and motor responses that accompany ethanol
      intoxication do not seem to be directly associated with differential hedonic
      properties of the drug at this stage of development.

PMID- 17452299
TI  - Lack of aldehyde dehydrogenase ameliorates oxidative stress induced by single
      dose ethanol administration in mouse liver.
AB  - Polymorphism of aldehyde dehydrogenase 2 (ALDH2), denoted ALDH2*2, is far more
      common in East Asian countries. Acetaldehyde, an intermediate metabolite of
      ethanol, is metabolized very slowly in people who have ALDH2*2, as the mutated
      ALDH2 lacks acetaldehyde metabolizing activity. On the other hand, it is well
      established that metabolism of ethanol causes oxidative stress in liver tissue.
      To examine the consequences of this polymorphism on ethanol-induced oxidative
      stress in liver tissue, we conducted a study using Aldh2 knockout mice. Aldh2+/+
      and Aldh2-/- mice were orally administered ethanol at a dose of 5g/kg body
      weight. Levels of malondialdehyde, an indicator of oxidative stress, and
      glutathione, a key antioxidant, in liver tissue were analyzed 0-24h after
      administration. Levels of malondialdehyde were significantly lower in Aldh2-/-
      mice than in Aldh2+/+ mice at 12h after injection, while levels of glutathione
      were higher in Aldh2-/- mice than in Aldh2+/+ mice at 6 and 12h after injection.
      Our results suggest that a lack of ALDH ameliorates ethanol-induced oxidative
      stress in liver tissue.

PMID- 17452300
TI  - The past, presence and future of ADMA in nephrology.
AB  - Kakimoto and Akazawa, first isolated and identified asymmetric dimethylarginine
      (ADMA) from human urine in 1970. They speculated that ADMA, and its structural
      isomer symmetrical dimethylarginine (SDMA), "may be important for the study of
      various pathological states". It took 22 years before this hypothesis
      materialized in form of the seminal paper by Vallance et al. who advanced the
      idea that ADMA accumulation may be a cardiovascular risk factor in chronic kidney
      disease (CKD). In the last 15 years the relationship between ADMA and adverse
      cardiovascular outcomes has been thoroughly investigated in more than 600
      published reports. These studies have shown that ADMA does not only correlate
      with traditional and non-traditional risk factors but also, independently of
      other risk factors, is strongly associated with clinical measures of
      cardiovascular burden such as intima-media thickness (IMT) of the carotid artery
      and left ventricular mass. Furthermore, cohort studies in both the general
      population and the dialysis population demonstrated a strong and independent link
      between ADMA, all-cause mortality and cardiovascular events. Last but not least,
      ADMA predicts the progression of CKD. This burgeoning body experimental and
      clinical studies form a fairly coherent framework indicating that ADMA is not
      only a marker but also a potent mediator of endothelial dysfunction and
      atherosclerosis as well as a solid predictor of mortality in selected patient
      populations. This article reviews the role of ADMA as a marker and mediator in
      cardiovascular disease in the setting of CKD and summarizes the effect of
      different renal replacement therapies as well as the effect on ADMA levels of
      commonly used drugs in nephrology. We conclude with remarks on the usefulness of
      ADMA as a marker in the clinical setting as well as for emerging therapeutic
      strategies.

PMID- 17452301
TI  - [French citizens do not know much about their kidneys... results of a nationwide
      survey on renal diseases].
AB  - Prevalence of chronic renal disease increases in France and in the world mainly
      because of ageing and diabetes mellitus. Early diagnosis and treatment of chronic
      renal disease allows significant slowing of the speed of degradation of
      glomerular filtration rate and may postpone or alleviate initiation of dialysis,
      an expensive and time consuming therapy. For the first time in France in October
      2005, a campaign of information to improve awareness of French citizens on renal
      diseases was organised. A survey was conducted by BVA in a sample of the French
      population to evaluate their degree of knowledge on renal diseases. Our study
      showed that French citizens do not know much about anatomical and physiological
      considerations concerning their kidneys. They are not aware of symptoms revealing
      renal disease or therapy available in case of kidney failure. Almost one third of
      the persons interviewed are directly or indirectly touched by renal diseases. It
      seems that efforts should be made to better information of French citizens on
      renal diseases as a first step towards improvement of chronic renal failure
      treatment strategy.

PMID- 17452302
TI  - [HemoCue: preliminary considerations about its use in hemodialysis].
AB  - HemoCue Hb 201+ is a portable photometric analyser providing easy, rapid and
      accurate determination of hemoglobin from arterial, venous or capillary blood. It
      is worth that dialysis units have knowledge of its use for a close hematologic
      monitoring of their patients and a judicious management of erythropoietin (EPO).
      For the autodialysis <<out hospital>> centers, it allows a flexibility that
      private laboratories cannot have in daily practice. Therefore authors present
      this device and the evaluation they obtained from 148 hemoglobin measures. Then
      they expose the advantages and the indications of its use.

PMID- 17452303
TI  - [Efficiency of rituximab treatment for recurrence of membranous glomerulopathy
      after renal transplantation].
AB  - Idiopathic membranous glomerulonephritis (MGN) is a rare cause of end-stage renal
      failure, which can lead to chronic hemodialysis. This glomerulopathy can recur
      after renal transplantation despite immunosuppressive therapy. To date, there is
      no confirmed therapy for treatment of renal grafts after recurrence of MGN.
      Herein, we report on a 27-year-old man who underwent cadaveric renal
      transplantation for MGN in September 2001. At 2 months posttransplant, a renal
      biopsy showed membranous deposition on immunofluorescence staining evocative of
      recurrence of MGN. Proteinuria developed progressively and, at one year, was
      estimated at 7.65 g/24 h, with hypoalbuminemia of 24 g/l. This persisted despite
      symptomatic treatment with anti-proteinuric agents (enalapril 20 mg/day and
      irbesartan 75 mg/day) and atorvastatin (10 mg/day). By March 2004, his
      proteinuria was 11 g/day; therefore, therapy with rituximab (monoclonal anti
      CD20) at 375 mg/m(2) weekly was initiated for four consecutive weeks, followed by
      the same dosage every four months for one year. Biological controls performed two
      weeks after the fourth infusion of rituximab showed a fall in proteinuria,
      assessed at 1 g/24 h, with albuminemia of 29 g/l and normalized lipidic results.
      A renal biopsy performed 6 months after the first infusion was unchanged. Follow
      up at 30 months showed consistent remission of membranous nephropathy,
      demonstrated by a serum creatinine level of 150 mumol/L, microalbuminuria of 107
      mg/24 h and normal albuminemia of 43.7 g/l. There were no side effects; in
      particular, no infectious complications occurred, despite CD19 lymphocytes being
      still negative after 30 months. Monoclonal CD-20 antibodies have shown efficacy
      against MGN compared to conventional therapies in native kidneys. It has recently
      been shown that CD20 mRNA is overexpressed in the renal interstitium in patients
      suffering from MGN and that the interstitial infiltrates is mainly composed of B
      cell lymphocytes in these patients. These data may explain the efficiency of
      rituximab in these circumstances.

PMID- 17452304
TI  - [A case of renal paradoxical embolism].
AB  - Acute renal failure due to paradoxical embolism is exceptionally reported. A new
      case gives the opportunity to review mechanisms, diagnosis and therapeutic
      issues. A 49-year-old woman without medical history is admitted for crural venous
      thrombosis and acute pulmonary embolism. At day 2, a left flank acute pain with
      fever, doubling of plasma creatinine, and controlateral recurrence at day 12,
      leads to diagnosis of acute bilateral renal infarction only at day 20.
      Paradoxical embolism is then suspected and confirmed by transoesophageal contrast
      echocardiography, disclosing patent foramen ovale with right-to-left shunt. Nine
      months later, successful percutaneous closure of patent foramen ovale with
      Amplatzer PFO occluder 25 mm allows subsequent discontinuation of oral
      anticoagulation. Diagnostic criteria for paradoxical embolism are present in our
      case. If this mechanism is often discussed in cryptogenic cerebrovascular stroke
      of young patients, it is exceptionally reported as responsible for clinical renal
      disease, particularly acute renal failure (whereas anatomical renal involvement
      is not unfrequent). The clue is the difficulty to suspect and confirm renal
      infarction, especially when classical causes of cardiac embolism are lacking. The
      relevance is the opportunity to save renal tissue in the acute phase, and to
      close patent foramen ovale (currently most often percutaneously) weeks or months
      after the acute bout.

PMID- 17452306
TI  - [Management of patients with severe head injury in Hungary, in 2002].
AB  - In Hungary, epidemiological and clinical data regarding brain injury were rather
      scarce. The Hungarian Society for Neurotrauma aimed to make a nation-wide study
      about the number and the mortality of patients with severe head trauma, the
      organization of management, the diagnostics and monitoring in use, and finally
      about the clinical practice of management. A national survey was carried out with
      questionnaires asking about data of 2001, and a prospective, three-month-long
      data collection based on case studies was also executed in 2002. The Hungarian
      National Ambulance and Emergency Service centralized information gathering on
      rescue, and transportation. To collect data of hospital care, a network of
      regional coordinators and hospital communicators was developed. The responders
      covered 76% of the hospital neurotrauma care in the country. The number of brain
      trauma patients was close to 14,000 per year: 71.3% mild, 19.4% moderate, and
      9.4% severe trauma. According to prospective study the mortality of those
      patients who were admitted as severe head injury patients was 55% and the
      mortality of those who got into severe condition later was 35% during the acute
      care. These data showed much worse outcome than those published in Western
      European countries and North America. In the background the authors found
      communication disorder between prehospital and hospital care, extreme long time
      spent until the patients got to the first CT-exam and to the definitive care. The
      implementation of Hungarian and international head trauma guidelines did not
      spread widely.

PMID- 17452307
TI  - [Stem cell theory of colorectal cancer and its connection with molecular
      biological data].
AB  - Colorectal cancer is the second leading cause of death in Hungary as well as in
      the developed countries. The high cancer prevalence of the gastrointestinal tract
      is the result of the rapid turnover of epithelial cells and exposure to dietary
      toxins. Adult stem cells are in the lime-light of the medicine. The adult stem
      cells and tumor cells resemble to each other on the basis of their properties,
      like self-renewal and proliferation. Cancer is believed to be a disease of stem
      cells. Recent years have seen major advances in our understanding of location
      (niche), life cycle, regulation (Wnt/beta-catenin signaling pathway) and markers
      (mathusashi-1, beta-catenin) of gastrointestinal stem cells. The exact role of
      adult stem cells in intestinal carcinogenesis is open for debate. New works
      suggest the role for inflammation-induced engraftment of circulating marrow
      derived stem cells in colorectal carcinogenesis. The causes of malignant
      transformation of local or engrafting bone marrow-derived stem cells are
      mutations (APC, MMR genes) or methylation (CDKN2A, p16/INK4a, MGMT, MLH1). The
      spread of dysplastic cells (bottom-up, top-down hypothesis) is also ambiguous.

PMID- 17452308
TI  - [Evaluation of the EuroSCORE model in the patient population of our department of
      cardiac surgery].
AB  - INTRODUCTION: The objective of current study is the evaluation of the accuracy
      and precision of EuroSCORE in the population of those patients undergone cardiac
      surgery in our department. MATERIAL AND METHODS: We have analyzed the data of
      1839 consecutive patients who had their operations between 1/January 2003 and
      31/December 2005. We have compared the mortality rates predicted preoperatively
      by additive and logistic EuroSCORE with the actual 30-day mortality figures. On
      statistical analysis the discriminative accuracy of the methods has been defined
      with the use of C-statistics. The calibration and precision of the methods have
      been checked by the Hosmer-Lemeshow statistics. RESULTS: The overall mortality
      rate in the above period was 3.3%. Additive and logistic EuroSCORE predicted 4.1
      +/- 2.8 and 4.5 +/- 6.1%, consecutively. Based on the C-statistics the area below
      the Receiver Operating Characteristic curve has measured 0.699 (0.629-0.769) and
      0.711 (0.642-0.779). The kappa 2 value for the Hosmer-Lemeshow statistics has
      proved 6.5 ( p = 0.475) and 12.5 ( p = 0.131). CONCLUSION: Logistic EuroSCORE has
      appropriate discriminative power and satisfactory precision, whilst the accuracy
      of additive EuroSCORE only comes near to the acceptable level, but at the same
      time it has an adequate calibration value. These results suggest that logistic
      EuroSCORE is more suitable for the preoperative risk assessment of these
      patients.

PMID- 17452309
TI  - [Common occurrence of non-alcoholic fatty liver disease and cholecystolithiasis].
AB  - INTRODUCTION: Non-Alcoholic Fatty Liver Disease is an acquired metabolic disease
      of the liver caused by accumulation of triglycerides in hepatocytes that is
      followed by necrobiotic inflammatory reaction, fibrosis and cirrhosis. Obesity,
      insulin resistance, diabetes mellitus and hyperlipidaemia are important
      pathogenetic factors of the process. It is known that among patients with
      cholecystolithiasis and diabetes mellitus in their anamnesis complications of
      cholecystolithiasis occur much more frequently like among patients without
      diabetes. AIM: The aim of the study is observation of the incidence of
      cholecystolithiasis and its complications in patients with Non-Alcoholic Fatty
      Liver Disease and comparison of cholecystolithiasis incidence between healthy
      population and population with Non-Alcoholic Fatty Liver Disease. METHODS:
      Abdominal ultrasonographical findings were analysed in patients hospitalised at
      our department and in outpatients, patients with severe accompanied diseases were
      excluded of the analysis. The analysed basic file of patients could be considered
      as a selected file. The independence of the two examined variables was measured
      by chi(2) test. RESULTS: Steatosis was described in 38% of the examined patients,
      cholecystolithiasis was described in 16% of patients. Cholecystolithiasis and its
      complications occur two times more frequently in patients with Non-Alcoholic
      Fatty Liver Disease (33%) like Non-Alcoholic Fatty Liver Disease in patients with
      cholecystolithiasis (16%). Complications of cholecystolithiasis occur more
      frequently among patients with Non-Alcoholic Fatty Liver Disease like in healthy
      individuals. The chi(2) test did not bring significant results concerning the
      independence of cholecystolithiasis and Non-Alcoholic Fatty Liver Disease.
      CONCLUSION: Pathogenetic factors of Non-Alcoholic Fatty Liver Disease participate
      in the pathogenesis of cholecystolithiasis. Their common pathogenetic factors
      bring about that the formation of cholecystolithiasis is probably faster than the
      progression of steatosis.

PMID- 17452310
TI  - [Gastric micropneumatosis: a rare endoscopic entity].
AB  - The rarely described gastric micropneumatosis is caused by accumulating air in
      the mucus membrane. It may associate mainly with Helicobacter pylori positive
      atrophic gastritis or with pneumatosis due to gas producing bacteria or non
      infectious causes. In our case the disorder was diagnosed in a 69 years old
      patient, taking clopidogrel, living in a nursing home, with history of
      hypertension, general arteriosclerosis, cerebral infarction, who was admitted to
      our department because of melaena and hematemesis. Upper endoscopy revealed a map
      like, slightly raised, palm-sized area with yellowish spots on the posterior wall
      of the markedly inflamed stomach at the level of fundus - corpus border. Based on
      histology findings, that showed empty spaces among corpus glands, 10-20 microm in
      diameter, with no epithelial lining, the diagnosis was gastric micropneumatosis.
      The impaired mucosal integrity caused by mesenteric ischaemia and repeated
      vomiting were supposed as possible etiological factors, because 72 hours after
      the patient had stopped vomiting, control endoscopy showed regression, and the
      empty spaces were no more detectable in the histology samples. By this case
      report the authors would like to draw attention to a seldom diagnosed gastric
      injury, and discuss the factors that may predispose the development of gastric
      micropneumatosis.

PMID- 17452311
TI  - [Chronic hepatitis C].

PMID- 17452313
TI  - [In defence of women against HPV-infection].

PMID- 17452315
TI  - Reovirus binding determinants in junctional adhesion molecule-A.
AB  - Junctional adhesion molecule-A (JAM-A) serves as a serotype-independent receptor
      for mammalian orthoreoviruses (reoviruses). The membrane-distal immunoglobulin
      like D1 domain of JAM-A is required for homodimerization and binding to reovirus
      attachment protein sigma1. We employed a structure-guided mutational analysis of
      the JAM-A dimer interface to identify determinants of reovirus binding. We
      purified mutant JAM-A ectodomains for solution-phase and surface plasmon
      resonance binding studies and expressed mutant forms of full-length JAM-A in
      Chinese hamster ovary cells to assess reovirus binding and infectivity. Mutation
      of residues in the JAM-A dimer interface that participate in salt-bridge or
      hydrogen-bond interactions with apposing JAM-A monomers abolishes the capacity of
      JAM-A to form dimers. JAM-A mutants incapable of dimer formation form complexes
      with the sigma1 head that are indistinguishable from wild-type JAM-A-sigma1 head
      complexes, indicating that sigma1 binds to JAM-A monomers. Residues Glu(61) and
      Lys(63) of beta-strand C and Leu(72) of beta-strand C' in the dimer interface are
      required for efficient JAM-A engagement of strain type 3 Dearing sigma1. Mutation
      of neighboring residues alters the kinetics of the sigma1-JAM-A binding
      interaction. Prototype reovirus strains type 1 Lang and type 2 Jones share
      similar, although not identical, binding requirements with type 3 Dearing. These
      results indicate that reovirus engages JAM-A monomers via residues found mainly
      on beta-strands C and C' of the dimer interface and raise the possibility that
      the distinct disease phenotypes produced in mice following infection with
      different strains of reovirus are in part attributable to differences in contacts
      with JAM-A.

PMID- 17452316
TI  - Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth
      factor-like repeat A of low density lipoprotein receptor decreases receptor
      recycling and increases degradation.
AB  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of
      hepatic low density lipoprotein receptors (LDLR), the major route of clearance of
      circulating cholesterol. Gain-of-function mutations in PCSK9 cause
      hypercholesterolemia and premature atherosclerosis, whereas loss-of-function
      mutations result in hypocholesterolemia and protection from heart disease.
      Recombinant human PCSK9 binds the LDLR on the surface of cultured hepatocytes and
      promotes degradation of the receptor after internalization. Here we localized the
      site of binding of PCSK9 within the extracellular domain of the LDLR and
      determined the fate of the receptor after PCSK9 binding. Recombinant human PCSK9
      interacted in a sequence-specific manner with the first epidermal growth factor
      like repeat (EGF-A) in the EGF homology domain of the human LDLR. Similar binding
      specificity was observed between PCSK9 and purified EGF-A. Binding to EGF-A was
      calcium-dependent and increased dramatically with reduction in pH from 7 to 5.2.
      The addition of PCSK9, but not heat-inactivated PCSK9, to the medium of cultured
      hepatocytes resulted in redistribution of the receptor from the plasma membrane
      to lysosomes. These data are consistent with a model in which PCSK9 binding to
      EGF-A interferes with an acid-dependent conformational change required for
      receptor recycling. As a consequence, the LDLR is rerouted from the endosome to
      the lysosome where it is degraded.

PMID- 17452317
TI  - Association of the Tim14.Tim16 subcomplex with the TIM23 translocase is crucial
      for function of the mitochondrial protein import motor.
AB  - Tim14 and Tim16 are essential components of the import motor of the mitochondrial
      TIM23 preprotein translocase. Tim14 contains a J domain in the matrix space that
      is anchored in the inner membrane by a transmembrane segment. Tim16 is a J
      related protein with a moderately hydrophobic segment at its N terminus. The J
      and J-like domains function in the regulation of the ATPase activity of the Hsp70
      chaperone of the import motor. We report here on the role of the hydrophobic
      segments of Tim16 and Tim14 in the TIM23 translocase. Yeast cells lacking the
      hydrophobic N-terminal segment in either Tim16 or Tim14 are viable but show
      growth defects and decreased import rates of matrix-targeted preproteins into
      mitochondria. The interaction of the Tim14.Tim16 complex with the core complex of
      the TIM23 translocase is destabilized in these cells. In particular, the N
      terminal domain of Tim16 is crucial for the interaction of the Tim14.Tim16
      complex with the TIM23 preprotein translocase. Deletion of hydrophobic segments
      in both, Tim16 and Tim14, is lethal. We conclude that import into the matrix
      space of mitochondria requires association of the co-chaperones Tim16 and Tim14
      with the TIM23 preprotein translocase.

PMID- 17452318
TI  - Nicotinic acid receptor agonists differentially activate downstream effectors.
AB  - Nicotinic acid remains the most effective therapeutic agent for the treatment and
      prevention of atherosclerosis resulting from low high density lipoprotein
      cholesterol. The therapeutic actions of nicotinic acid are mediated by GPR109A, a
      Gi protein-coupled receptor, expressed primarily on adipocytes, Langerhans cells,
      and macrophage. Unfortunately, a severe, cutaneous flushing side effect limits
      its use and patient compliance. The mechanism of high density lipoprotein
      elevation is not clearly established but assumed to be influenced by an
      inhibition of lipolysis in the adipose. The flushing side effect appears to be
      mediated by the release of prostaglandin D2 from Langerhans cells in the skin. We
      hypothesized that the signal transduction pathways mediating the anti-lipolytic
      and prostaglandin D2/flushing pathways are distinct and that agonists may be
      identified that are capable of selectively eliciting the therapeutic, anti
      lipolytic pathway while avoiding the activation of the parallel flush-inducing
      pathway. We have identified a number of GPR109A pyrazole agonists that are
      capable of fully inhibiting lipolysis in vitro and in vivo and not only fail to
      elicit a flushing response but can antagonize the ability of nicotinic acid to
      elicit a flush response in vivo. In contrast to flushing agonists, exposure of
      cells expressing GPR109A to the non-flushing agonists fails to induce
      internalization of the receptor or to activate ERK 1/2 mitogen-activated protein
      kinase phosphorylation.

PMID- 17452319
TI  - Characterization of Arabidopsis thaliana SufE2 and SufE3: functions in
      chloroplast iron-sulfur cluster assembly and Nad synthesis.
AB  - In this study we characterize two novel chloroplast SufE-like proteins from
      Arabidopsis thaliana. Other SufE-like proteins, including the previously
      described A. thaliana CpSufE, participate in sulfur mobilization for Fe-S
      biosynthesis through activation of cysteine desulfurization by NifS-like
      proteins. In addition to CpSufE, the Arabidopsis genome encodes two other
      proteins with SufE domains, SufE2 and SufE3. SufE2 has plastid targeting
      information. Purified recombinant SufE2 could activate the cysteine desulfurase
      activity of CpNifS 40-fold. SufE2 expression was flower-specific and high in
      pollen; we therefore hypothesize that SufE2 has a specific function in pollen Fe
      S cluster biosynthesis. SufE3, also a plastid targeted protein, was expressed at
      low levels in all major plant organs. The mature SufE3 contains two domains, one
      SufE-like and one with similarity to the bacterial quinolinate synthase, NadA.
      Indeed SufE3 displayed both SufE activity (stimulating CpNifS cysteine
      desulfurase activity 70-fold) and quinolinate synthase activity. The full-length
      protein was shown to carry a highly oxygen-sensitive (4Fe-4S) cluster at its NadA
      domain, which could be reconstituted by its own SufE domain in the presence of
      CpNifS, cysteine and ferrous iron. Knock-out of SufE3 in Arabidopsis is
      embryolethal. We conclude that SufE3 is the NadA enzyme of A. thaliana, involved
      in a critical step during NAD biosynthesis.

PMID- 17452320
TI  - An assembled complex IV maintains the stability and activity of complex I in
      mammalian mitochondria.
AB  - In the mammalian mitochondrial electron transfer system, the majority of
      electrons enter at complex I, go through complexes III and IV, and are finally
      delivered to oxygen. Previously we generated several mouse cell lines with
      suppressed expression of the nuclearly encoded subunit 4 of complex IV. This led
      to a loss of assembly of complex IV and its defective function. Interestingly, we
      found that the level of assembled complex I and its activity were also
      significantly reduced, whereas levels and activity of complex III were normal or
      up-regulated. The structural and functional dependence of complex I on complex IV
      was verified using a human cell line carrying a nonsense mutation in the
      mitochondrially encoded complex IV subunit 1 gene. Our work documents that,
      although there is no direct electron transfer between them, an assembled complex
      IV helps to maintain complex I in mammalian cells.

PMID- 17452321
TI  - Identification of a streptococcal octapeptide motif involved in acute rheumatic
      fever.
AB  - Acute rheumatic fever is a serious autoimmune sequela of pharyngitis caused by
      certain group A streptococci. One mechanism applied by streptococcal strains
      capable of causing acute rheumatic fever is formation of an autoantigenic complex
      with human collagen IV. In some geographic regions with a high incidence of acute
      rheumatic fever pharyngeal carriage of group C and group G streptococci prevails.
      Examination of such strains revealed the presence of M-like surface proteins that
      bind human collagen. Using a peptide array and recombinant proteins with targeted
      amino acid substitutions, we could demonstrate that formation of collagen
      complexes during streptococcal infections depends on an octapeptide motif, which
      is present in collagen binding M and M-like proteins of different beta-hemolytic
      streptococcal species. Mice immunized with streptococcal proteins that contain
      the collagen binding octapeptide motif developed high serum titers of anti
      collagen antibodies. In sera of rheumatic fever patients such a collagen
      autoimmune response was accompanied by specific reactivity against the collagen
      binding proteins, linking the observed effect to clinical cases. Taken together,
      the data demonstrate that the identified octapeptide motif through its action on
      collagen plays a crucial role in the pathogenesis of rheumatic fever. Eradication
      of streptococci that express proteins with the collagen binding motif appears
      advisable for controlling rheumatic fever.

PMID- 17452322
TI  - Induction of the gal pathway and cellulase genes involves no transcriptional
      inducer function of the galactokinase in Hypocrea jecorina.
AB  - The Saccharomyces cerevisiae galactokinase ScGal1, a key enzyme for D-galactose
      metabolism, catalyzes the conversion of D-galactose to D-galactose 1-phosphate,
      whereas its catalytically inactive paralogue, ScGal3, activates the transcription
      of the GAL pathway genes. In Kluyveromyces lactis the transcriptional inducer
      function and the galactokinase activity are encoded by a single bifunctional
      KlGal1. Here, we investigated the cellular function of the single galactokinase
      GAL1 in the multicellular ascomycete Hypocrea jecorina (=Trichoderma reesei) in
      the induction of the gal genes and of the galactokinase-dependent induction of
      the cellulase genes by lactose (1,4-O-beta-D-galactopyranosyl-D-glucose). A
      comparison of the transcriptional response of a strain deleted in the gal1 gene
      (no putative transcriptional inducer and no galactokinase activity), a strain
      expressing a catalytically inactive GAL1 version (no galactokinase activity but a
      putative inducer function), and a strain expressing the Escherichia coli galK (no
      putative transcriptional inducer but galactokinase activity) showed that, in
      contrast to the two yeasts, both the GAL1 protein and the galactokinase activity
      are fully dispensable for induction of the Leloir pathway gene gal7 by D
      galactose and that only the galactokinase activity is required for cellulase
      induction by lactose. The data document a fundamental difference in the
      mechanisms by which yeasts and multicellular fungi respond to the presence of D
      galactose, showing that the Gal1/Gal3-Gal4-Gal80-dependent regulatory circuit
      does not operate in multicellular fungi.

PMID- 17452323
TI  - Definition by functional and structural analysis of two malonyl-CoA sites in
      carnitine palmitoyltransferase 1A.
AB  - Carnitine palmitoyltransferase 1 (CPT1) catalyzes the conversion of palmitoyl-CoA
      to palmitoylcarnitine in the presence of l-carnitine, thus facilitating the entry
      of fatty acids to mitochondria, in a process that is physiologically inhibited by
      malonyl-CoA. To examine the mechanism of CPT1 liver isoform (CPT1A) inhibition by
      malonyl-CoA, we constructed an in silico model of both its NH2- and COOH-terminal
      domains. Two malonyl-CoA binding sites were found. One of these, the "CoA site"
      or "A site," is involved in the interactions between NH2- and COOH-terminal
      domains and shares the acyl-CoA hemitunnel. The other, the "opposite-to-CoA site"
      or "O site," is on the opposite side of the enzyme, in the catalytic channel. The
      two sites share the carnitine-binding locus. To prevent the interaction between
      NH2- and COOH-terminal regions, we produced CPT1A E26K and K561E mutants. A
      double mutant E26K/K561E (swap), which was expected to conserve the interaction,
      was also produced. Inhibition assays showed a 12-fold decrease in the sensitivity
      (IC50) toward malonyl-CoA for CPT1A E26K and K561E single mutants, whereas swap
      mutant reverts to wild-type IC50 value. We conclude that structural interaction
      between both domains is critical for enzyme sensitivity to malonyl-CoA inhibition
      at the "A site." The location of the "O site" for malonyl-CoA binding was
      supported by inhibition assays of expressed R243T mutant. The model is also
      sustained by kinetic experiments that indicated linear mixed type malonyl-CoA
      inhibition for carnitine. Malonyl-CoA alters the affinity of carnitine, and there
      appears to be an exponential inverse relation between carnitine Km and malonyl
      CoA IC50.

PMID- 17452324
TI  - Localization of an NH(2)-terminal disease-causing mutation hot spot to the
      "clamp" region in the three-dimensional structure of the cardiac ryanodine
      receptor.
AB  - A region between residues 414 and 466 in the cardiac ryanodine receptor (RyR2)
      harbors more than half of the known NH(2)-terminal mutations associated with
      cardiac arrhythmias and sudden death. To gain insight into the structural basis
      of this NH(2)-terminal mutation hot spot, we have determined its location in the
      three-dimensional structure of RyR2. Green fluorescent protein (GFP), used as a
      structural marker, was inserted into the middle of this mutation hot spot after
      Ser-437 in the RyR2 sequence. The resultant GFP-RyR2 fusion protein, RyR2(S437
      GFP,) was expressed in HEK293 cells and characterized using Ca(2+) release,
      [(3)H]ryanodine binding, and single cell Ca(2+) imaging studies. These functional
      analyses revealed that RyR2(S437-GFP) forms a caffeine- and ryanodine-sensitive
      Ca(2+) release channel that possesses Ca(2+) and caffeine dependence of
      activation indistinguishable from that of wild type (wt) RyR2. HEK293 cells
      expressing RyR2(S437-GFP) displayed a propensity for store overload-induced
      Ca(2+) release similar to that in cells expressing RyR2-wt. The three-dimensional
      structure of the purified RyR2(S437-GFP) was reconstructed using cryo-electron
      microscopy and single particle image processing. Subtraction of the three
      dimensional reconstructions of RyR2-wt and RyR2(S437-GFP) revealed the location
      of the inserted GFP, and hence the NH(2)-terminal mutation hot spot, in a region
      between domains 5 and 9 in the clamp-shaped structure. This location is close to
      a previously mapped central disease-causing mutation site located in a region
      between domains 5 and 6. These results, together with findings from previous
      studies, suggest that the proposed interactions between the NH(2)-terminal and
      central regions of RyR2 are likely to take place between domains 5 and 6 and that
      the clamp-shaped structure, which shows substantial conformational differences
      between the closed and open states, is highly susceptible to disease-causing
      mutations.

PMID- 17452325
TI  - Activation of Mps1 promotes transforming growth factor-beta-independent Smad
      signaling.
AB  - The primary intracellular mediators of TGF-beta signaling are the Smad proteins.
      Phosphorylation of R-Smad at the C-terminal SSXS motif by the activated TGF-beta
      type I receptor kinase triggers a conformation change in R-Smad and facilitates
      complex formation between R-Smad and Smad4, which shuttle into the nucleus where
      they interact with DNA and other transcription factors to regulate gene
      expression. In an attempt to identify proteins interacting with activated Smad
      signaling complex, we discovered that Mps1, a protein kinase that plays important
      roles in normal mitotic progression and mitotic checkpoint signaling, co-purifies
      with this complex. We demonstrated that Smad2 and Smad3 but not Smad4 are
      substrates of Mps1 in vitro and in vivo. Mps1 phosphorylates Smad2 and Smad3 at
      the SSXS motif in their C-terminal regions in vitro and in vivo. Disruption of
      microtubule networks by nocodazole activates Mps1 and promotes TGF-beta
      independent activation of Smad signaling. We found that Mps1 is involved in
      turning on Smad signaling by phosphorylating R-Smads. Our results reveal a novel
      functional link between Mps1 and Smads in a non-canonical Smad signaling pathway.

PMID- 17452326
TI  - The proton electrochemical gradient across the plasma membrane of yeast is
      necessary for phospholipid flip.
AB  - Recently, two members of the P4 family of P-type ATPases, Dnf1p and Dnf2p, were
      shown to be necessary for the internalization (flip) of fluorescent, 7-nitrobenz
      2-oxa-1,3-diazol-4-yl(NBD)-labeled phospholipids across the plasma membrane of
      Saccharomyces cerevisiae. In the current study, we have demonstrated that ATP
      hydrolysis is not sufficient for phospholipid flip in the absence of the proton
      electrochemical gradient across the plasma membrane. This requirement was
      demonstrated by two independent means. First, collapse of the plasma membrane
      proton electrochemical gradient by the protonophore, carbonyl cyanide m
      chlorophenylhydrazone (CCCP) almost completely blocked NBD-phospholipid flip
      while only moderately reducing the cytosolic ATP concentration. Second, strains
      with point mutations in PMA1, which encodes the plasma membrane proton pump that
      generates the proton electrochemical gradient, are defective in NBD-PC flip,
      whereas their cytosolic ATP content is actually increased. These results
      establish that the proton electrochemical gradient is required for NBD
      phospholipid flip across the plasma membrane of yeast and raise the question
      whether it contributes an additional required driving force or whether it
      functions as a regulatory signal.

PMID- 17452327
TI  - Human TRBP and PACT directly interact with each other and associate with dicer to
      facilitate the production of small interfering RNA.
AB  - Mammalian Dicer interacts with double-stranded RNA-binding protein TRBP or PACT
      to mediate RNA interference and micro-RNA processing. TRBP and PACT are
      structurally related but exert opposite regulatory activities on PKR. It is not
      understood whether TRBP and PACT are simultaneously required for Dicer. Here we
      show that TRBP directly interacts with PACT in vitro and in mammalian cells. TRBP
      and PACT form a triple complex with Dicer and facilitate the production of small
      interfering RNA (siRNA) by Dicer. Knockdown of both TRBP and PACT in cultured
      cells leads to significant inhibition of gene silencing mediated by short hairpin
      RNA but not by siRNA, suggesting that TRBP and PACT function primarily at the
      step of siRNA production. Taken together, these findings indicate that human TRBP
      and PACT directly interact with each other and associate with Dicer to stimulate
      the cleavage of double-stranded or short hairpin RNA to siRNA. Our work
      significantly alters the current model for the assembly and function of the Dicer
      containing complex that generates siRNA and micro-RNA in human.

PMID- 17452328
TI  - Calcium inhibition and calcium potentiation of Orai1, Orai2, and Orai3 calcium
      release-activated calcium channels.
AB  - The recent discoveries of Stim1 and Orai proteins have shed light on the
      molecular makeup of both the endoplasmic reticulum Ca(2+) sensor and the calcium
      release-activated calcium (CRAC) channel, respectively. In this study, we
      investigated the regulation of CRAC channel function by extracellular Ca(2+) for
      channels composed primarily of Orai1, Orai2, and Orai3, by co-expressing these
      proteins together with Stim1, as well as the endogenous channels in HEK293 cells.
      As reported previously, Orai1 or Orai2 resulted in a substantial increase in CRAC
      current (I(crac)), but Orai3 failed to produce any detectable Ca(2+)-selective
      currents. However, sodium currents measured in the Orai3-expressing HEK293 cells
      were significantly larger in current density than Stim1-expressing cells.
      Moreover, upon switching to divalent free external solutions, Orai3 currents were
      considerably more stable than Orai1 or Orai2, indicating that Orai3 channels
      undergo a lesser degree of depotentiation. Additionally, the difference between
      depotentiation from Ca(2+) and Ba(2+) or Mg(2+) solutions was significantly less
      for Orai3 than for Orai1 or -2. Nonetheless, the Na(+) currents through Orai1,
      Orai2, and Orai3, as well as the endogenous store-operated Na(+) currents in
      HEK293 cells, were all inhibited by extracellular Ca(2+) with a half-maximal
      concentration of approximately 20 mum. We conclude that Orai1, -2, and -3
      channels are similarly inhibited by extracellular Ca(2+), indicating similar
      affinities for Ca(2+) within the selectivity filter. Orai3 channels appeared to
      differ from Orai1 and -2 in being somewhat resistant to the process of Ca(2+)
      depotentiation.

PMID- 17452329
TI  - Toward understanding the cationicity of defensins. Arg and Lys versus their
      noncoded analogs.
AB  - Human defensins are a family of small antimicrobial proteins found predominantly
      in leukocytes and epithelial cells that play important roles in the innate and
      adaptive immune defense against microbial infection. The most distinct molecular
      feature of defensins is cationicity, manifested by abundant Arg and/or Lys
      residues in their sequences. Sequence analysis indicates that Arg is strongly
      selected over Lys in alpha-defensins but not in beta-defensins. To understand
      this Arg/Lys disparity in defensins, we chemically synthesized human alpha
      defensin 1 (HNP1) and several HNP1 analogs where three Arg residues were replaced
      by each of the following six alpha-amino acids: Lys, ornithine (Orn),
      diaminobutyric acid (Dab), diaminopropionic acid (Dap), N,N-dimethyl-Lys
      ((diMe)Lys), and homo-Arg ((homo)Arg). In addition, we prepared human beta
      defensin 1 (hBD1) and (Lys-->Arg)hBD1 in which all four Lys residues were
      substituted for Arg. Bactericidal activity assays revealed the following. 1) Arg
      containing HNP1 and (Lys-->Arg)hBD1 are functionally better than Lys-HNP1 and
      hBD1, respectively; the difference between Arg and Lys is more evident in the
      alpha-defensin than in the beta-defensin and is more evident at low salt
      concentrations than at high salt concentrations. 2) For HNP1, the Arg/Lys
      disparity is much more pronounced with Staphylococcus aureus than with
      Escherichia coli, and the Arg-rich HNP1 kills bacteria faster than its Lys-rich
      analog. 3) Arg and Lys appear to have optimal chain lengths for bacterial killing
      as shortening Lys or lengthening Arg in HNP1 invariably becomes functionally
      deleterious. Our findings provide insights into the Arg/Lys disparity in
      defensins, and shed light on the cationicity of defensins with respect to their
      antimicrobial activity and specificity.

PMID- 17452330
TI  - Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via
      MAPK signaling pathways.
AB  - Migration and proliferation of smooth muscle cells are key to a number of
      physiological and pathological processes, including wound healing and the
      narrowing of the vessel wall. Previous work has shown links between inflammatory
      stimuli and vascular smooth muscle cell proliferation and migration through
      mitogen-activated protein kinase (MAPK) activation, although the molecular
      mechanisms of this process are poorly understood. Here we report that tribbles-1,
      a recently described modulator of MAPK activation, controls vascular smooth
      muscle cell proliferation and chemotaxis via the Jun kinase pathway. Our findings
      demonstrate that this regulation takes place via direct interactions between
      tribbles-1 and MKK4/SEK1, a Jun activator kinase. The activity of this kinase is
      dependent on tribbles-1 levels, whereas the activation and the expression of
      MKK4/SEK1 are not. In addition, tribbles-1 expression is elevated in human
      atherosclerotic arteries when compared with non-atherosclerotic controls,
      suggesting that this protein may play a role in disease in vivo. In summary, the
      data presented here suggest an important regulatory role for trb-1 in vascular
      smooth muscle cell biology.

PMID- 17452331
TI  - A molecular link between E2F-1 and the MAPK cascade.
AB  - Transcription factor E2F-1 mediates apoptosis and suppresses tumorigenesis. The
      mechanisms by which E2F-1 functions in these processes are largely unclear. We
      report here that E2F-1 acts as a transcriptional regulator of MKP-2 (MAPK
      phosphatase-2), a dual specificity protein phosphatase (DUSP4) with stringent
      substrate specificity for MAPKs. We show that E2F-1 is required for the cellular
      apoptotic response to oxidative damage. MKP-2 is greatly increased following
      oxidative stress, and E2F-1 is necessary for that induction. We found that E2F-1
      is physically associated with the MKP-2 promoter and can transactivate the
      promoter of the MKP-2 gene. Specifically, E2F-1 binds to a perfect palindromic
      motif in the MKP-2 promoter. Finally, we show that this E2F-1/MKP-2 pathway
      mediates apoptosis under oxidative stress and that MKP-2 suppresses tumor
      formation in nude mice. Our findings demonstrate that E2F-1 is a transcriptional
      activator of MKP-2 and that MKP-2 is an essential cell death mediator in the E2F
      1 pathway. Characterization of MKP-2 as a cell death mediator may lead to the
      development of new strategies for cancer treatment.

PMID- 17452332
TI  - Stabilization of p73 by nuclear IkappaB kinase-alpha mediates cisplatin-induced
      apoptosis.
AB  - In response to DNA damage, p53 and its homolog p73 have a function antagonistic
      to NF-kappaB in deciding cell fate. Here, we show for the first time that p73,
      but not p53, is stabilized by physical interaction with nuclear IkappaB kinase
      (IKK)-alpha to enhance cisplatin (CDDP)-induced apoptosis. CDDP caused a
      significant increase in the amounts of nuclear IKK-alpha and p73alpha in human
      osteosarcoma-derived U2OS cells. Ectopic expression of IKK-alpha prolonged the
      half-life of p73 by inhibiting its ubiquitination and thereby enhancing its
      transactivation and pro-apoptotic activities. Consistent with these results,
      small interfering RNA-mediated knockdown of endogenous IKK-alpha inhibited the
      CDDP-mediated accumulation of p73alpha. The kinase-deficient mutant form of IKK
      alpha interacted with p73alpha, but failed to stabilize it. Furthermore, CDDP
      mediated accumulation of endogenous p73alpha was not detected in mouse embryonic
      fibroblasts (MEFs) prepared from IKK-alpha-deficient mice, and CDDP sensitivity
      was significantly decreased in IKK-alpha-deficient MEFs compared with wild-type
      MEFs. Thus, our results strongly suggest that the nuclear IKK-alpha-mediated
      accumulation of p73alpha is one of the novel molecular mechanisms to induce
      apoptotic cell death in response to CDDP, which may be particularly important in
      killing tumor cells with p53 mutation.

PMID- 17452333
TI  - Glutathione is recruited into the nucleus in early phases of cell proliferation.
AB  - We have studied the possible correlation between nuclear glutathione distribution
      and the progression of the cell cycle. The former was studied by confocal
      microscopy using 5-chloromethyl fluorescein diacetate and the latter by flow
      cytometry and protein expression of Id2 and p107. In proliferating cells, when
      41% of them were in the S+G(2)/M phase of the cell cycle GSH was located mainly
      in the nucleus. When cells reached confluence (G(0)/G(1)) GSH was localized in
      the cytoplasm with a perinuclear distribution. The nucleus/cytoplasm fluorescence
      ratio for GSH reached a maximal mean value of 4.2 +/- 0.8 at 6 h after cell
      plating. A ratio higher than 2 was maintained during exponential cell growth. In
      the G(0)/G(1) phase of the cell cycle, the nucleus/cytoplasm GSH ratio decreased
      to values close to 1. We report here that cells concentrate GSH in the nucleus in
      the early phases of cell growth, when most of the cells are in an active division
      phase, and that GSH redistributes uniformly between the nucleus and the cytoplasm
      when cells reach confluence.

PMID- 17452334
TI  - Ubiquitous lens alpha-, beta-, and gamma-crystallins accumulate in anuran cornea
      as corneal crystallins.
AB  - Corneal epithelium is known to have high levels of some metabolic enzymes such as
      aldehyde dehydrogenase in mammals, gelsolin in zebrafish, and alpha-enolase in
      several species. Analogous to lens crystallins, these enzymes and proteins are
      referred to as corneal crystallins, although their precise function is not
      established in any species. Although it is known that after lentectomy, the outer
      cornea undergoes transdifferentiation to regenerate a lens only in anuran
      amphibians, major proteins expressed in an anuran cornea have not been
      identified. This study therefore aimed to identify the major corneal proteins in
      the Indian toad (Bufo melanostictus) and the Indian frog (Rana tigrina). Soluble
      proteins of toad and frog corneas were resolved on two-dimensional gels and
      identified by matrix-assisted laser desorption ionization time-of-flight/time-of
      flight and electrospray ionization quadrupole time-of-flight. We report that
      anuran cornea is made up of the full complement of ubiquitous lens alpha-, beta-,
      and gamma-crystallins, mainly localized in the corneal epithelium. In addition,
      some taxon-specific lens crystallins and novel proteins, such as alpha- or beta
      enolase/tau-crystallin, were also identified. Our data present a unique case of
      the anuran cornea where the same crystallins are used in the lens and in the
      cornea, thus supporting the earlier idea that crystallins are essential for the
      visual functions of the cornea as they perform for the lens. High levels of lens
      alpha-, beta-, and gamma-crystallins have not been reported in the cornea of any
      species studied so far and may offer a possible explanation for their inability
      to regenerate a lens after lentectomy. Our data that anuran cornea has an
      abundant quantity of almost all the lens crystallins are consistent with its
      ability to form a lens, and this connection is worthy of further studies.

PMID- 17452335
TI  - Fukutin-related protein associates with the sarcolemmal dystrophin-glycoprotein
      complex.
AB  - Mutations in fukutin-related protein (FKRP) give rise to mild and more severe
      forms of muscular dystrophy. FKRP patients have reduced glycosylation of the
      extracellular protein dystroglycan, and FKRP itself shows sequence similarity to
      glycosyltransferases, implicating FKRP in the processing of dystroglycan.
      However, FKRP localization is controversial, and no FKRP complexes are known, so
      any FKRP-dystroglycan link remains elusive. Here, we demonstrate a novel FKRP
      localization in vivo; in mouse, both endogenous and recombinant FKRP are present
      at the sarcolemma. Biochemical analyses revealed that mouse muscle FKRP and
      dystroglycan co-enrich and co-fractionate, indicating that FKRP coexists with
      dystroglycan in the native dystrophin-glycoprotein complex. Furthermore, FKRP
      sedimentation shifts with dystroglycan in disease models involving the dystrophin
      glycoprotein complex, and sarcolemmal FKRP immunofluorescence mirrors that of
      dystroglycan in muscular dystrophy mice, suggesting that FKRP localization may be
      mediated by dystroglycan. These data offer the first evidence of an FKRP complex
      in muscle and suggest that FKRP may influence the glycosylation status of
      dystroglycan from within the sarcolemmal dystrophin-glycoprotein complex.

PMID- 17452336
TI  - PO(2)-dependent differential regulation of multidrug resistance 1 gene expression
      by the c-Jun NH2-terminal kinase pathway.
AB  - Hypoxia-induced multidrug resistance 1 (MDR1) gene expression is known to be
      mediated by c-Jun NH(2)-terminal kinase (JNK) activation. However, the molecular
      mechanisms underlying this action of JNK remain elusive. On the contrary, there
      has been increasing evidence for a negative correlation of JNK activity with MDR1
      expression under normoxic conditions. Here, we present evidence that the JNK
      pathway represses MDR1 expression in normoxia and activates MDR1 expression in
      hypoxia. Our data show that JNK pathway-induced MDR1 repression in normoxia is
      mediated by increased c-Jun binding to activator protein 1 site, located in the
      MDR1 promoter, and requires the activity of histone deacetylase 5. In contrast,
      JNK pathway-induced MDR1 activation in hypoxia is independent of the activator
      protein 1 site. Rather, this action is dependent on increased hypoxia-inducible
      factor 1 (HIF1) binding to the hypoxia response element in the MDR1 promoter,
      which is promoted by the interaction of HIF1alpha with c-Jun in the nucleus and
      requires the activity of the p300/CBP (CREB-binding protein) coactivator.

PMID- 17452337
TI  - ELMOD2 is an Arl2 GTPase-activating protein that also acts on Arfs.
AB  - Regulatory GTPases in the Ras superfamily employ a cycle of alternating GTP
      binding and hydrolysis, controlled by guanine nucleotide exchange factors and
      GTPase-activating proteins (GAPs), as essential features of their actions in
      cells. Studies of these GAPs and guanine nucleotide exchange factors have
      provided important insights into our understanding of GTPase signaling and
      biology. Within the Ras superfamily, the Arf family is composed of 30 members in
      mammals, including 22 Arf-like (Arl) proteins. Much less is known about the
      mechanisms of cell regulation by Arls than by Arfs. We report the purification
      from bovine testis of an Arl2 GAP and its identity as ELMOD2, a protein with no
      previously described function. ELMOD2 is one of six human proteins that contain
      an ELMO domain, and a second member, ELMOD1, was also found to have Arl2 GAP
      activity. Surprisingly, ELMOD2 also exhibited GAP activity against Arf proteins
      even though it does not contain the canonical Arf GAP sequence signature. The
      broader specificity of ELMOD2, as well as the previously described role for ELMO1
      and ELMO2 in linking Arf6 and Rac1 signaling, suggests that ELMO family members
      may play a more general role in integrating signaling pathways controlled by Arls
      and other GTPases.

PMID- 17452338
TI  - Structural determinants for ligand-receptor conformational selection in a peptide
      G protein-coupled receptor.
AB  - G protein coupled receptors (GPCRs) modulate the majority of physiological
      processes through specific intermolecular interactions with structurally diverse
      ligands and activation of differential intracellular signaling. A key issue yet
      to be resolved is how GPCRs developed selectivity and diversity of ligand binding
      and intracellular signaling during evolution. We have explored the structural
      basis of selectivity of naturally occurring gonadotropin-releasing hormones
      (GnRHs) from different species in the single functional human GnRH receptor. We
      found that the highly variable amino acids in position 8 of the naturally
      occurring isoforms of GnRH play a discriminating role in selecting receptor
      conformational states. The human GnRH receptor has a higher affinity for the
      cognate GnRH I but a lower affinity for GnRH II and GnRHs from other species
      possessing substitutions for Arg(8). The latter were partial agonists in the
      human GnRH receptor. Mutation of Asn(7.45) in transmembrane domain (TM) 7 had no
      effect on GnRH I affinity but specifically increased affinity for other GnRHs and
      converted them to full agonists. Using molecular modeling and site-directed
      mutagenesis, we demonstrated that the highly conserved Asn(7.45) makes
      intramolecular interactions with a highly conserved Cys(6.47) in TM 6, suggesting
      that disruption of this intramolecular interaction induces a receptor
      conformational change which allosterically alters ligand specific binding sites
      and changes ligand selectivity and signaling efficacy. These results reveal GnRH
      ligand and receptor structural elements for conformational selection, and support
      co-evolution of GnRH ligand and receptor conformations.

PMID- 17452339
TI  - Reaction mechanism of glutathione synthetase from Arabidopsis thaliana: site
      directed mutagenesis of active site residues.
AB  - Glutathione is essential for maintaining the intracellular redox environment and
      is synthesized from gamma-glutamylcysteine, glycine, and ATP by glutathione
      synthetase (GS). To examine the reaction mechanism of a eukaryotic GS, 24
      Arabidopsis thaliana GS (AtGS) mutants were kinetically characterized. Within the
      gamma-glutamylcysteine/glutathione-binding site, the S153A and S155A mutants
      displayed less than 4-fold changes in kinetic parameters with mutations of Glu
      220 (E220A/E220Q), Gln-226 (Q226A/Q226N), and Arg-274 (R274A/R274K) at the distal
      end of the binding site resulting in 24-180-fold increases in the K(m) values for
      gamma-glutamylcysteine. Substitution of multiple residues interacting with ATP
      (K313M, K367M, and E429A/E429Q) or coordinating magnesium ions to ATP
      (E148A/E148Q, N150A/N150D, and E371A) yielded inactive protein because of
      compromised nucleotide binding, as determined by fluorescence titration. Other
      mutations in the ATP-binding site (E371Q, N376A, and K456M) resulted in greater
      than 30-fold decreases in affinity for ATP and up to 80-fold reductions in
      turnover rate. Mutation of Arg-132 and Arg-454, which are positioned at the
      interface of the two substrate-binding sites, affected the enzymatic activity
      differently. The R132A mutant was inactive, and the R132K mutant decreased k(cat)
      by 200-fold; however, both mutants bound ATP with K(d) values similar to wild
      type enzyme. Minimal changes in kinetic parameters were observed with the R454K
      mutant, but the R454A mutant displayed a 160-fold decrease in k(cat). In
      addition, the R132K, R454A, and R454K mutations elevated the K(m) value for
      glycine up to 11-fold. Comparison of the pH profiles and the solvent deuterium
      isotope effects of A. thaliana GS and the Arg-132 and Arg-454 mutants also
      suggest distinct mechanistic roles for these residues. Based on these results, a
      catalytic mechanism for the eukaryotic GS is proposed.

PMID- 17452340
TI  - Arabidopsis Teosinte Branched1-like 1 regulates axillary bud outgrowth and is
      homologous to monocot Teosinte Branched1.
AB  - Axillary bud outgrowth is controlled by developmental and environmental signals
      through the integrated action of hormones and other factors that probably
      regulate the cell cycle in the buds. While hormonal regulators have been studied
      extensively, less is known about downstream mechanisms regulating bud outgrowth.
      The TCP domain protein Teosinte Branched1 (TB1) is a putative transcriptional
      regulator that represses bud outgrowth in grasses. Phylogenetic analyses have
      indicated that three hypothetical Arabidopsis (Arabidopsis thaliana) proteins,
      TCP1, TCP12 and TCP18 [Teosinte Branched1-Like 1 (TBL1)], are closely related to
      monocot TB1 proteins. A reverse genetics approach was used to identify TBL1 and
      TCP12 mutants to assess the function of the hypothetical proteins. No obvious
      phenotype was observed in tcp12 mutants. tbl1 null mutants exhibited a non
      pleiotropic hyperbranching phenotype that was due to enhanced outgrowth of
      primary and secondary buds. The role of TBL1 as a repressor of bud outgrowth was
      supported by TBL1 mRNA accumulation: abundance was high in unelongated buds, and
      decreased to low levels in buds that were elongating. Analyses of TBL1 expression
      in hormone signaling mutants with aberrant branching suggest that TBL1 acts
      downstream of auxin and the MAX-related hormone to coordinate bud outgrowth. The
      data are consistent with Arabidopsis TBL1 providing functionality similar to
      monocot TB1, and highlight the conservation of mechanisms regulating branching
      across large evolutionary distances.

PMID- 17452341
TI  - Regulatory properties of potato-Arabidopsis hybrid ADP-glucose pyrophosphorylase.
AB  - In higher plants, ADP-glucose pyrophosphorylase (ADPGlc-PPase) is a
      heterotetrameric enzyme comprised of two small and two large subunits. Potato
      Arabidopsis hybrid ADPGlc-PPases were generated and their regulatory properties
      analyzed. We show that ADPGlc-PPase subunits from two different species can
      interact, producing active enzymes with new regulatory properties. Depending on
      the subunit combinations, hybrid heterotetramers showed responses to allosteric
      effectors [3-phosphoglycerate (3-PGA) and Pi] in the micromolar or millimolar
      range. While hybrid potato small subunit (PSS) and the Arabidopsis large subunit
      APL1 showed an extremely sensitive response to 3-PGA and Pi, hybrid
      PSS/Arabidopsis APL2 was very insensitive to them. Intermediate responses were
      determined for other subunit combinations.

PMID- 17452342
TI  - Potential role of annexin AnnAt1 from Arabidopsis thaliana in pH-mediated
      cellular response to environmental stimuli.
AB  - Plant annexins, Ca(2+)- and membrane-binding proteins, are probably implicated in
      the cellular response to stress resulting from acidification of cytosol. To
      understand how annexins can contribute to cellular ion homeostasis, we
      investigated the pH-induced changes in the structure and function of recombinant
      annexin AnnAt1 from Arabidopsis thaliana. The decrease of pH from 7.0 to 5.8
      reduced the time of the formation of ion channels by AnnAt1 in artificial lipid
      membranes from 3.5 h to 15-20 min and increased their unitary conductance from 32
      to 63 pS. These changes were accompanied by an increase in AnnAt1 hydrophobicity
      as revealed by hydrophobicity predictions, by an increase in fluorescence of 2-(p
      toluidino)naphthalene-6-sulfonic acid (TNS) bound to AnnAt1 and fluorescence
      resonance energy transfer from AnnAt1 tryptophan residues to TNS. Concomitant
      lipid partition of AnnAt1 at acidic pH resulted in its partial protection from
      proteolytic digestion. Secondary structures of AnnAt1 determined by circular
      dichroism and infrared spectroscopy were also affected by lowering the pH from
      7.2 to 5.2. These changes were characterized by an increase in beta-sheet content
      at the expense of alpha-helical structures, and were accompanied by reversible
      formation of AnnAt1 oligomers as probed by ultracentrifugation in a sucrose
      gradient. A further decrease of pH from 5.2 to 4.5 or lower led to the formation
      of irreversible aggregates and loss of AnnAt1 ionic conductance. Our findings
      suggest that AnnAt1 can sense changes of the pH milieu over the pH range from 7
      to 5 and respond by changes in ion channel conductance, hydrophobicity, secondary
      structure of the protein and formation of oligomers. Further acidification
      irreversibly inactivated AnnAt1. We suggest that the pH-sensitive ion channel
      activity of AnnAt1 may play a role in intracellular ion homeostasis.

PMID- 17452343
TI  - Excessive expression of the plant kinesin TBK5 converts cortical and perinuclear
      microtubules into a radial array emanating from a single focus.
AB  - TBK5 is a plant-specific kinesin constantly expressed in tobacco BY-2 cells. An
      analysis of the distribution of green fluorescent protein-tagged TBK5 (GFP-TBK5)
      transiently expressed in BY-2 protoplasts revealed that TBK5 could associate with
      microtubules in vivo. GFP-TBK5 often assembled to form a single particle when
      accumulated in cells. The particle was located in close proximity to the nucleus,
      and its formation was accompanied by the development of a radial array of
      microtubules emanating from it and the loss of cortical microtubules. Microtubule
      depolymerization by treatment with propyzamide inhibited particle formation and
      stimulated the formation of dispersed aggregates of GFP-TBK5. Through expression
      of different TBK5 mutants as GFP fusions, the motor domain, two separated coiled
      coil domains and the C-terminal domain of TBK5 were identified as the domains
      playing essential roles in particle formation. Mutants with putatively non-motile
      motor domains or lacking the C-terminal domain were localized to cortical and
      perinuclear microtubules, whereas those lacking either of the coiled-coil domains
      were preferentially distributed around the nucleus and along perinuclar
      microtubules. Further, the deletion of one of the coiled-coil domains or the C
      terminal domain was sufficient to inhibit the propyzamide-induced formation of
      dispersed aggregates, whereas the mutation in the motor domain was not. These
      results led us to propose a model in which the particle is formed through the
      microtubule-based movement of GFP-TBK5 toward the nucleus and subsequent
      microtubule-independent aggregation based on coiled-coil interactions. The
      dramatic microtubule rearrangement would be explained if GFP-TBK5 relocated and
      gathered newly formed microtubules and/or microtubule-nucleating units.

PMID- 17452344
TI  - OligoCalc: an online oligonucleotide properties calculator.
AB  - We developed OligoCalc as a web-accessible, client-based computational engine for
      reporting DNA and RNA single-stranded and double-stranded properties, including
      molecular weight, solution concentration, melting temperature, estimated
      absorbance coefficients, inter-molecular self-complementarity estimation and
      intra-molecular hairpin loop formation. OligoCalc has a familiar 'calculator'
      look and feel, making it readily understandable and usable. OligoCalc
      incorporates three common methods for calculating oligonucleotide-melting
      temperatures, including a nearest-neighbor thermodynamic model for melting
      temperature. Since it first came online in 1997, there have been more than
      900,000 accesses of OligoCalc from nearly 200,000 distinct hosts, excluding
      search engines. OligoCalc is available at
      http://basic.northwestern.edu/biotools/OligoCalc.html, with links to the full
      source code, usage patterns and statistics at that link as well.

PMID- 17452345
TI  - PROMALS web server for accurate multiple protein sequence alignments.
AB  - Multiple sequence alignments are essential in homology inference, structure
      modeling, functional prediction and phylogenetic analysis. We developed a web
      server that constructs multiple protein sequence alignments using PROMALS, a
      progressive method that improves alignment quality by using additional homologs
      from PSI-BLAST searches and secondary structure predictions from PSIPRED. PROMALS
      shows higher alignment accuracy than other advanced methods, such as MUMMALS,
      ProbCons, MAFFT and SPEM. The PROMALS web server takes FASTA format protein
      sequences as input. The output includes a colored alignment augmented with
      information about sequence grouping, predicted secondary structures and
      positional conservation. The PROMALS web server is available at:
      http://prodata.swmed.edu/promals/

PMID- 17452346
TI  - Phylemon: a suite of web tools for molecular evolution, phylogenetics and
      phylogenomics.
AB  - Phylemon is an online platform for phylogenetic and evolutionary analyses of
      molecular sequence data. It has been developed as a web server that integrates a
      suite of different tools selected among the most popular stand-alone programs in
      phylogenetic and evolutionary analysis. It has been conceived as a natural
      response to the increasing demand of data analysis of many experimental
      scientists wishing to add a molecular evolution and phylogenetics insight into
      their research. Tools included in Phylemon cover a wide yet selected range of
      programs: from the most basic for multiple sequence alignment to elaborate
      statistical methods of phylogenetic reconstruction including methods for
      evolutionary rates analyses and molecular adaptation. Phylemon has several
      features that differentiates it from other resources: (i) It offers an integrated
      environment that enables the direct concatenation of evolutionary analyses, the
      storage of results and handles required data format conversions, (ii) Once an
      outfile is produced, Phylemon suggests the next possible analyses, thus guiding
      the user and facilitating the integration of multi-step analyses, and (iii) users
      can define and save complete pipelines for specific phylogenetic analysis to be
      automatically used on many genes in subsequent sessions or multiple genes in a
      single session (phylogenomics). The Phylemon web server is available at
      http://phylemon.bioinfo.cipf.es.

PMID- 17452347
TI  - The RNAz web server: prediction of thermodynamically stable and evolutionarily
      conserved RNA structures.
AB  - Many non-coding RNA genes and cis-acting regulatory elements of mRNAs contain RNA
      secondary structures that are critical for their function. Such functional RNAs
      can be predicted on the basis of thermodynamic stability and evolutionary
      conservation. We present a web server that uses the RNAz algorithm to detect
      functional RNA structures in multiple alignments of nucleotide sequences. The
      server provides access to a complete and fully automatic analysis pipeline that
      allows not only to analyze single alignments in a variety of formats, but also to
      conduct complex screens of large genomic regions. Results are presented on a
      website that is illustrated by various structure representations and can be
      downloaded for local view. The web server is available at:
      rna.tbi.univie.ac.at/RNAz.

PMID- 17452348
TI  - eTBLAST: a web server to identify expert reviewers, appropriate journals and
      similar publications.
AB  - Authors, editors and reviewers alike use the biomedical literature to identify
      appropriate journals in which to publish, potential reviewers for papers or
      grants, and collaborators (or competitors) with similar interests. Traditionally,
      this process has either relied upon personal expertise and knowledge or upon a
      somewhat unsystematic and laborious process of manually searching through the
      literature for trends. To help with these tasks, we report three utilities that
      parse and summarize the results of an abstract similarity search to find
      appropriate journals for publication, authors with expertise in a given field,
      and documents similar to a submitted query. The utilities are based upon a
      program, eTBLAST, designed to identify similar documents within literature
      databases such as (but not limited to) MEDLINE. These services are freely
      accessible through the Internet at
      http://invention.swmed.edu/etblast/etblast.shtml, where users can upload a file
      or paste text such as an abstract into the browser interface.

PMID- 17452349
TI  - INFO-RNA--a server for fast inverse RNA folding satisfying sequence constraints.
AB  - INFO-RNA is a new web server for designing RNA sequences that fold into a user
      given secondary structure. Furthermore, constraints on the sequence can be
      specified, e.g. one can restrict sequence positions to a fixed nucleotide or to a
      set of nucleotides. Moreover, the user can allow violations of the constraints at
      some positions, which can be advantageous in complicated cases. The INFO-RNA web
      server allows biologists to design RNA sequences in an automatic manner. It is
      clearly and intuitively arranged and easy to use. The procedure is fast, as most
      applications are completed within seconds and it proceeds better and faster than
      other existing tools. The INFO-RNA web server is freely available at
      http://www.bioinf.uni-freiburg.de/Software/INFO-RNA/

PMID- 17452350
TI  - MolProbity: all-atom contacts and structure validation for proteins and nucleic
      acids.
AB  - MolProbity is a general-purpose web server offering quality validation for 3D
      structures of proteins, nucleic acids and complexes. It provides detailed all
      atom contact analysis of any steric problems within the molecules as well as
      updated dihedral-angle diagnostics, and it can calculate and display the H-bond
      and van der Waals contacts in the interfaces between components. An integral step
      in the process is the addition and full optimization of all hydrogen atoms, both
      polar and nonpolar. New analysis functions have been added for RNA, for
      interfaces, and for NMR ensembles. Additionally, both the web site and major
      component programs have been rewritten to improve speed, convenience, clarity and
      integration with other resources. MolProbity results are reported in multiple
      forms: as overall numeric scores, as lists or charts of local problems, as
      downloadable PDB and graphics files, and most notably as informative, manipulable
      3D kinemage graphics shown online in the KiNG viewer. This service is available
      free to all users at http://molprobity.biochem.duke.edu.

PMID- 17452351
TI  - Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG
      causes distinct replication stalling phenotypes.
AB  - The mechanism of mitochondrial DNA replication is a subject of intense debate.
      One model proposes a strand-asynchronous replication in which both strands of the
      circular genome are replicated semi-independently while the other model proposes
      both a bidirectional coupled leading- and lagging-strand synthesis mode and a
      unidirectional mode in which the lagging-strand is initially laid-down as RNA by
      an unknown mechanism (RITOLS mode). Both the strand-asynchronous and RITOLS model
      have in common a delayed synthesis of the DNA-lagging strand. Mitochondrial DNA
      is replicated by a limited set of proteins including DNA polymerase gamma (POLG)
      and the helicase Twinkle. Here, we report the effects of expression of various
      catalytically deficient mutants of POLG1 and Twinkle in human cell culture. Both
      groups of mutants reduced mitochondrial DNA copy number by severe replication
      stalling. However, the analysis showed that while induction of POLG1 mutants
      still displayed delayed lagging-strand synthesis, Twinkle-induced stalling
      resulted in maturated, essentially fully double-stranded DNA intermediates. In
      the latter case, limited inhibition of POLG with dideoxycytidine restored the
      delay between leading- and lagging-strand synthesis. The observed cause-effect
      relationship suggests that Twinkle-induced stalling increases lagging-strand
      initiation events and/or maturation mimicking conventional strand-coupled
      replication.

PMID- 17452352
TI  - Differential regulation of repeated histone genes during the fission yeast cell
      cycle.
AB  - The histone genes are highly reiterated in a wide range of eukaryotic genomes.
      The fission yeast, Schizosaccharomyces pombe, has three pairs of histone H3-H4
      genes: hht1+-hhf1+, hht2+-hhf2+ and hht3+-hhf3+. While the deduced amino acid
      sequences are identical, it remains unknown whether transcriptional regulation
      differs among the three pairs. Here, we report the transcriptional properties of
      each H3-H4 gene pair during the cell cycle. The levels of transcripts of hht1+
      hhf1+ and hht3+-hhf3+ pairs and hhf2+ are increased at S-phase, while that of
      hht2+ remains constant throughout the cell cycle. We showed that the GATA-type
      transcription factor, Ams2, binds to the promoter regions of core histone genes
      in an AACCCT-box-dependent manner and is required for activation of S-phase
      specific transcription. Furthermore, we found that Ams2-depletion stimulates
      feedback regulation of histone transcripts, mainly up-regulating the basal levels
      of hht2+-hhf2+ transcription, which are normally down-regulated by Hip1 and Slm9,
      homologs of the human histone chaperone, HIRA. These observations provide insight
      into the molecular mechanisms of differential regulation of transcripts from
      repeated histone genes in the fission yeast.

PMID- 17452353
TI  - Genomewide and biochemical analyses of DNA-binding activity of Cdc6/Orc1 and Mcm
      proteins in Pyrococcus sp.
AB  - The origin of DNA replication (oriC) of the hyperthermophilic archaeon Pyrococcus
      abyssi contains multiple ORB and mini-ORB repeats that show sequence similarities
      to other archaeal ORB (origin recognition box). We report here that the binding
      of Cdc6/Orc1 to a 5 kb region containing oriC in vivo was highly specific both in
      exponential and stationary phases, by means of chromatin immunoprecipitation
      coupled with hybridization on a whole genome microarray (ChIP-chip). The oriC
      region is practically the sole binding site for the Cdc6/Orc1, thereby
      distinguishing oriC in the 1.8 M bp genome. We found that the 5 kb region
      contains a previously unnoticed cluster of ORB and mini-ORB repeats in the gene
      encoding the small subunit (dp1) for DNA polymerase II (PolD). ChIP and the gel
      retardation analyses further revealed that Cdc6/Orc1 specifically binds both of
      the ORB clusters in oriC and dp1. The organization of the ORB clusters in the dp1
      and oriC is conserved during evolution in the order Thermococcales, suggesting a
      role in the initiation of DNA replication. Our ChIP-chip analysis also revealed
      that Mcm alters the binding specificity to the oriC region according to the
      growth phase, consistent with its role as a licensing factor.

PMID- 17452354
TI  - Position and distance specificity are important determinants of cis-regulatory
      motifs in addition to evolutionary conservation.
AB  - Computational discovery of cis-regulatory elements remains challenging. To cope
      with the high false positives, evolutionary conservation is routinely used.
      However, conservation is only one of the attributes of cis-regulatory elements
      and is neither necessary nor sufficient. Here, we assess two additional
      attributes--positional and inter-motif distance specificity--that are critical
      for interactions between transcription factors. We first show that for a greater
      than expected fraction of known motifs, the genes that contain the motifs in
      their promoters in a position-specific or distance-specific manner are related,
      both in function and/or in expression pattern. We then use the position and
      distance specificity to discover novel motifs. Our work highlights the importance
      of distance and position specificity, in addition to the evolutionary
      conservation, in discovering cis-regulatory motifs.

PMID- 17452355
TI  - Defining the mode, energetics and specificity with which a macrocyclic
      hexaoxazole binds to human telomeric G-quadruplex DNA.
AB  - Oxazole-containing macrocycles represent a promising class of anticancer agents
      that target G-quadruplex DNA. We report the results of spectroscopic studies
      aimed at defining the mode, energetics and specificity with which a hexaoxazole
      containing macrocycle (HXDV) binds to the intramolecular quadruplex formed by the
      human telomeric DNA model oligonucleotide d(T2AG3)4 in the presence of potassium
      ions. HXDV binds solely to the quadruplex nucleic acid form, but not to the
      duplex or triplex form. HXDV binds d(T2AG3)4 with a stoichiometry of two drug
      molecules per quadruplex, with these binding reactions being coupled to the
      destacking of adenine residues from the terminal G-tetrads. HXDV binding to
      d(T2AG3)4 does not alter the length of the quadruplex. These collective
      observations are indicative of a nonintercalative 'terminal capping' mode of
      interaction in which one HXDV molecule binds to each end of the quadruplex. The
      binding of HXDV to d(T2AG3)4 is entropy driven, with this entropic driving force
      reflecting contributions from favorable drug-induced alterations in the
      configurational entropy of the host quadruplex as well as in net hydration. The
      'terminal capping' mode of binding revealed by our studies may prove to be a
      general feature of the interactions between oxazole-containing macrocyclic
      ligands (including telomestatin) and intramolecular DNA quadruplexes.

PMID- 17452356
TI  - Non-EST-based prediction of novel alternatively spliced cassette exons with cell
      signaling function in Caenorhabditis elegans and human.
AB  - To better understand the complex role that alternative splicing plays in
      intracellular signaling, it is important to catalog the numerous splice variants
      involved in signal transduction. Therefore, we developed PASE (Prediction of
      Alternative Signaling Exons), a computational tool to identify novel alternative
      cassette exons that code for kinase phosphorylation or signaling protein-binding
      sites. We first applied PASE to the Caenorhabditis elegans genome. In this
      organism, our algorithm had an overall specificity of > or =76.4%, including 33
      novel cassette exons that we experimentally verified. We then used PASE to
      analyze the human genome and made 804 predictions, of which 308 were found as
      alternative exons in the transcript database. We experimentally tested 384 of the
      remaining unobserved predictions and discovered 26 novel human exons for a total
      specificity of > or =41.5% in human. By using a test set of known alternatively
      spliced signaling exons, we determined that the sensitivity of PASE is
      approximately 70%. GO term analysis revealed that our exon predictions were found
      in the introns of known signal transduction genes more often than expected by
      chance, indicating PASE enriches for splice variants that function in signaling
      pathways. Overall, PASE was able to uncover 59 novel alternative cassette exons
      in C. elegans and humans through a genome-wide ab initio prediction method that
      enriches for exons involved in signaling.

PMID- 17452357
TI  - The C-terminal loop of the homing endonuclease I-CreI is essential for site
      recognition, DNA binding and cleavage.
AB  - Meganucleases are sequence-specific endonucleases with large cleavage sites that
      can be used to induce efficient homologous gene targeting in cultured cells and
      plants. These enzymes open novel perspectives for genome engineering in a wide
      range of fields, including gene therapy. A new crystal structure of the I-CreI
      dimer without DNA has allowed the comparison with the DNA-bound protein. The C
      terminal loop displays a different conformation, which suggests its implication
      in DNA binding. A site-directed mutagenesis study in this region demonstrates
      that whereas the C-terminal helix is negligible for DNA binding, the final C
      terminal loop is essential in DNA binding and cleavage. We have identified two
      regions that comprise the Ser138-Lys139 and Lys142-Thr143 pairs whose double
      mutation affect DNA binding in vitro and abolish cleavage in vivo. However, the
      mutation of only one residue in these sites allows DNA binding in vitro and
      cleavage in vivo. These findings demonstrate that the C-terminal loop of I-CreI
      endonuclease plays a fundamental role in its catalytic mechanism and suggest this
      novel site as a region to take into account for engineering new endonucleases
      with tailored specificity.

PMID- 17452358
TI  - DNA sequence-specific recognition by a transcriptional regulator requires
      indirect readout of A-tracts.
AB  - The bacteriophage O29 transcriptional regulator p4 binds to promoters of
      different intrinsic activities. The p4-DNA complex contains two identical
      protomers that make similar interactions with the target sequence 5'-AACTTTTT-15
      bp-AAAATGTT-3'. To define how the various elements in the target sequence
      contribute to p4's affinity, we studied p4 binding to a series of mutated binding
      sites. The binding specificity depends critically on base pairs of the target
      sequence through both direct as well as indirect readout. There is only one
      specific contact between a base and an amino acid residue; other contacts take
      place with the phosphate backbone. Alteration of direct amino acid-base contacts,
      or mutation of non-contacted A.T base pairs at A-tracts abolished binding. We
      generated three 5 ns molecular dynamics (MD) simulations to investigate the basis
      for the p4-DNA complex specificity. Recognition is controlled by the protein and
      depends on DNA dynamic properties. MD results on protein-DNA contacts and the
      divergence of p4 affinity to modified binding sites reveal an inherent asymmetry,
      which is required for p4-specific binding and may be crucial for transcription
      regulation.

PMID- 17452359
TI  - The 1.4-A crystal structure of the S. pombe Pop2p deadenylase subunit unveils the
      configuration of an active enzyme.
AB  - Deadenylation is the first and probably also rate-limiting step of controlled
      mRNA decay in eukaryotes and therefore central for the overall rate of gene
      expression. In yeast, the process is maintained by the mega-Dalton Ccr4-Not
      complex, of which both the Ccr4p and Pop2p subunits are 3'-5' exonucleases
      potentially responsible for the deadenylation reaction. Here, we present the
      crystal structure of the Pop2p subunit from Schizosaccharomyces pombe determined
      to 1.4 A resolution and show that the enzyme is a competent ribonuclease with a
      tunable specificity towards poly-A. In contrast to S. cerevisiae Pop2p, the S.
      pombe enzyme contains a fully conserved DEDDh active site, and the high
      resolution allows for a detailed analysis of its configuration, including
      divalent metal ion binding. Functional data further indicates that the identity
      of the ions in the active site can modulate both activity and specificity of the
      enzyme, and finally structural superposition of single nucleotides and poly-A
      oligonucleotides provide insight into the catalytic cycle of the protein.

PMID- 17452360
TI  - Identification of conserved secondary structures and expansion segments in enod40
      RNAs reveals new enod40 homologues in plants.
AB  - enod40 is a plant gene that participates in the regulation of symbiotic
      interaction between leguminous plants and bacteria or fungi. Furthermore, it has
      been suggested to play a general role in non-symbiotic plant development.
      Although enod40 seems to have multiple functions, being present in many land
      plants, the molecular mechanisms of its activity are unclear; they may be
      determined though, by short peptides and/or RNA structures encoded in the enod40
      genes. We utilized conserved RNA structures in enod40 sequences to search
      nucleotide sequence databases and identified a number of new enod40 homologues in
      plant species that belong to known, but also, to yet unknown enod40-containing
      plant families. RNA secondary structure predictions and comparative sequence
      analysis of enod40 RNAs allowed us to determine the most conserved structural
      features, present in all known enod40 genes. Remarkably, the topology and
      evolution of one of the conserved structural domains are similar to those of the
      expansion segments found in structural RNAs such as rRNAs, RNase P and SRP RNAs.
      Surprisingly, the enod40 RNA structural elements are much more stronger conserved
      than the encoded peptides. This finding suggests that some general functions of
      enod40 gene could be determined by the encoded RNA structure, whereas short
      peptides may be responsible for more diverse functions found only in certain
      plant families.

PMID- 17452361
TI  - Solution structure of Domains IVa and V of the tau subunit of Escherichia coli
      DNA polymerase III and interaction with the alpha subunit.
AB  - The solution structure of the C-terminal Domain V of the tau subunit of E. coli
      DNA polymerase III was determined by nuclear magnetic resonance (NMR)
      spectroscopy. The fold is unique to tau subunits. Amino acid sequence
      conservation is pronounced for hydrophobic residues that form the structural core
      of the protein, indicating that the fold is representative for tau subunits from
      a wide range of different bacteria. The interaction between the polymerase
      subunits tau and alpha was studied by NMR experiments where alpha was incubated
      with full-length C-terminal domain (tau(C)16), and domains shortened at the C
      terminus by 11 and 18 residues, respectively. The only interacting residues were
      found in the C-terminal 30-residue segment of tau, most of which is structurally
      disordered in free tau(C)16. Since the N- and C-termini of the structured core of
      tau(C)16 are located close to each other, this limits the possible distance
      between alpha and the pentameric deltatau2gammadelta' clamp-loader complex and,
      hence, between the two alpha subunits involved in leading- and lagging-strand DNA
      synthesis. Analysis of an N-terminally extended construct (tau(C)22) showed that
      tau(C)14 presents the only part of Domains IVa and V of tau which comprises a
      globular fold in the absence of other interaction partners.

PMID- 17452362
TI  - Base-specific spin-labeling of RNA for structure determination.
AB  - To facilitate the measurement of intramolecular distances in solvated RNA
      systems, a combination of spin-labeling, electron paramagnetic resonance (EPR),
      and molecular dynamics (MD) simulation is presented. The fairly rigid spin label
      2,2,5,5-tetramethyl-pyrrolin-1-yloxyl-3-acetylene (TPA) was base and site
      specifically introduced into RNA through a Sonogashira palladium catalyzed cross
      coupling on column. For this purpose 5-iodo-uridine, 5-iodo-cytidine and 2-iodo
      adenosine phosphoramidites were synthesized and incorporated into RNA-sequences.
      Application of the recently developed ACE chemistry presented the main advantage
      to limit the reduction of the nitroxide to an amine during the oligonucleotide
      automated synthesis and thus to increase substantially the reliability of the
      synthesis and the yield of labeled oligonucleotides. 4-Pulse Electron Double
      Resonance (PELDOR) was then successfully used to measure the intramolecular spin
      spin distances in six doubly labeled RNA-duplexes. Comparison of these results
      with our previous work on DNA showed that A- and B-Form can be differentiated.
      Using an all-atom force field with explicit solvent, MD simulations gave results
      in good agreement with the measured distances and indicated that the RNA A-Form
      was conserved despite a local destabilization effect of the nitroxide label. The
      applicability of the method to more complex biological systems is discussed.

PMID- 17452363
TI  - Nucleoside alpha-thiotriphosphates, polymerases and the exonuclease III analysis
      of oligonucleotides containing phosphorothioate linkages.
AB  - The use of DNA polymerases to incorporate phosphorothioate linkages into DNA, and
      the use of exonuclease III to determine where those linkages have been
      incorporated, are re-examined in this work. The results presented here show that
      exonuclease III degrades single-stranded DNA as a substrate and digests through
      phosphorothioate linkages having one absolute stereochemistry, assigned (assuming
      inversion in the polymerase reaction) as S, but not the other absolute
      stereochemistry. This contrasts with a general view in the literature that
      exonuclease III favors double-stranded nucleic acid as a substrate and stops
      completely at phosphorothioate linkages. Furthermore, not all DNA polymerases
      appear to accept exclusively the (R) stereoisomer of nucleoside alpha
      thiotriphosphates [and not the (S) diastereomer], a conclusion inferred two
      decades ago by examination of five Family-A polymerases and a reverse
      transcriptase. This suggests that caution is appropriate when extrapolating the
      detailed behavior of one polymerase from the behaviors of other polymerases.
      Furthermore, these results provide constraints on how exonuclease III
      thiotriphosphate-polymerase combinations can be used to analyze the behavior of
      the components of a synthetic biology.

PMID- 17452365
TI  - RNAmmer: consistent and rapid annotation of ribosomal RNA genes.
AB  - The publication of a complete genome sequence is usually accompanied by
      annotations of its genes. In contrast to protein coding genes, genes for
      ribosomal RNA (rRNA) are often poorly or inconsistently annotated. This makes
      comparative studies based on rRNA genes difficult. We have therefore created
      computational predictors for the major rRNA species from all kingdoms of life and
      compiled them into a program called RNAmmer. The program uses hidden Markov
      models trained on data from the 5S ribosomal RNA database and the European
      ribosomal RNA database project. A pre-screening step makes the method fast with
      little loss of sensitivity, enabling the analysis of a complete bacterial genome
      in less than a minute. Results from running RNAmmer on a large set of genomes
      indicate that the location of rRNAs can be predicted with a very high level of
      accuracy. Novel, unannotated rRNAs are also predicted in many genomes. The
      software as well as the genome analysis results are available at the CBS web
      server.

PMID- 17452364
TI  - Actin-related protein Arp4 functions in kinetochore assembly.
AB  - The actin-related proteins (Arps) comprise a conserved protein family. Arp4p is
      found in large multisubunits of the INO80 and SWR1 chromatin remodeling complexes
      and in the NuA4 histone acetyltransferase complex. Here we show that arp4
      (arp4S23A/D159A) temperature-sensitive cells are defective in G2/M phase
      function. arp4 mutants are sensitive to the microtubule depolymerizing agent
      benomyl and arrest at G2/M phase at restrictive temperature. Arp4p is associated
      with centromeric and telomeric regions throughout cell cycle. Ino80p, Esa1p and
      Swr1p, components of the INO80, NuA4 and SWR1 complexes, respectively, also
      associate with centromeres. The association of many kinetochore components
      including Cse4p, a component of the centromere nucleosome, Mtw1p and Ctf3p is
      partially impaired in arp4 cells, suggesting that the G2/M arrest of arp4 mutant
      cells is due to a defect in formation of the chromosomal segregation apparatus.

PMID- 17452366
TI  - Mechanism for the TtDnaA-Tt-oriC cooperative interaction at high temperature and
      duplex opening at an unusual AT-rich region in Thermoanaerobacter tengcongensis.
AB  - Thermoanaerobacter tengcongensis is an anaerobic low-GC thermophilic bacterium.
      To further elucidate the replication initiation of chromosomal DNA at high
      temperature, the interaction between the replication initiator (TtDnaA) and the
      putative origin (Tt-oriC) in this thermophile was investigated. We found that
      efficient binding of TtDnaA to Tt-oriC at high temperature requires (i) at least
      two neighboring DnaA boxes, (ii) the specific feature of the TtDnaA Domain IV and
      (iii) the self-oligomerization of TtDnaA. Replacement of the TtDnaA Domain IV by
      the counterpart of Escherichia coli DnaA or disruption of its oligomerization by
      amino acid mutations (W9A/L20S) abolished the oriC-binding activity of TtDnaA at
      60 degrees C, but not at 37 degrees C. Moreover, ATP-TtDnaA, but not ADP-TtDnaA
      or the oligomerization-deficient mutants was able to unwind the Tt-oriC duplex.
      The minimal oriC required for this duplex opening in vitro was demonstrated to
      consist of DnaA boxes 1-8 and an unusual AT-rich region. Interestingly, although
      no typical ATP-DnaA box was found in this AT-rich region, it was exclusively
      bound by ATP-TtDnaA and acted as the duplex-opening and replication-initiation
      site. Taken together, we propose that oligomerization of ATP-DnaA and
      simultaneously binding of several DnaA boxes and/or AT-rich region may be
      generally required in replication initiation at high temperature.

PMID- 17452367
TI  - Regulation of B family DNA polymerase fidelity by a conserved active site
      residue: characterization of M644W, M644L and M644F mutants of yeast DNA
      polymerase epsilon.
AB  - To better understand the functions and fidelity of DNA polymerase epsilon (Pol
      epsilon), we report here on the fidelity of yeast Pol epsilon mutants with
      leucine, tryptophan or phenylalanine replacing Met644. The Met644 side chain
      interacts with an invariant tyrosine that contacts the sugar of the incoming
      dNTP. M644W and M644L Pol epsilon synthesize DNA with high fidelity, but M644F
      Pol epsilon has reduced fidelity resulting from strongly increased misinsertion
      rates. When Msh6-dependent repair of replication errors is defective, the
      mutation rate of a pol2-M644F strain is 16-fold higher than that of a strain with
      wild-type Pol epsilon. In conjunction with earlier studies of low-fidelity
      mutants with replacements for the homologous amino acid in yeast Pol alpha
      (L868M/F) and Pol delta (L612M), these data indicate that the active site
      location occupied by Met644 in Pol epsilon is a key determinant of replication
      fidelity by all three B family replicative polymerases. Interestingly, error
      specificity of M644F Pol epsilon is distinct from that of L868M/F Pol alpha or
      L612M Pol delta, implying that each polymerase has different active site
      geometry, and suggesting that these polymerase alleles may generate distinctive
      mutational signatures for probing functions in vivo.

PMID- 17452368
TI  - Guanines are a quartet's best friend: impact of base substitutions on the
      kinetics and stability of tetramolecular quadruplexes.
AB  - Parallel tetramolecular quadruplexes may be formed with short
      oligodeoxynucleotides bearing a block of three or more guanines. We analyze the
      properties of sequence variants of parallel quadruplexes in which each guanine of
      the central block was systematically substituted with a different base. Twelve
      types of substitutions were assessed in more than 100 different sequences. We
      conducted a comparative kinetic analysis of all tetramers. Electrospray mass
      spectrometry was used to count the number of inner cations, which is an indicator
      of the number of effective tetrads. In general, the presence of a single
      substitution has a strong deleterious impact on quadruplex stability, resulting
      in reduced quadruplex lifetime/thermal stability and in decreased association
      rate constants. We demonstrate extremely large differences in the association
      rate constants of these quadruplexes depending on modification position and type.
      These results demonstrate that most guanine substitutions are deleterious to
      tetramolecular quadruplex structure. Despite the presence of well-defined non
      guanine base quartets in a number of NMR and X-ray structures, our data suggest
      that most non-guanine quartets do not participate favorably in structural
      stability, and that these quartets are formed only by virtue of the docking
      platform provided by neighboring G-quartets. Two notable exceptions were found
      with 8-bromo-guanine (X) and 6-methyl-isoxanthopterin (P) substitutions, which
      accelerate quadruplex formation by a factor of 10 when present at the 5' end. The
      thermodynamic and kinetic data compiled here are highly valuable for the design
      of DNA quadruplex assemblies with tunable association/dissociation properties.

PMID- 17452369
TI  - Domain swapping between FEN-1 and XPG defines regions in XPG that mediate
      nucleotide excision repair activity and substrate specificity.
AB  - FEN-1 and XPG are members of the FEN-1 family of structure-specific nucleases,
      which share a conserved active site. FEN-1 plays a central role in DNA
      replication, whereas XPG is involved in nucleotide excision repair (NER). Both
      FEN-1 and XPG are active on flap structures, but only XPG cleaves bubble
      substrates. The spacer region of XPG is dispensable for nuclease activity on flap
      substrates but is required for NER activity and for efficient processing of
      bubble substrates. Here, we inserted the spacer region of XPG between the
      nuclease domains of FEN-1 to test whether this domain would be sufficient to
      confer XPG-like substrate specificity and NER activity on a related nuclease. The
      resulting FEN-1-XPG hybrid protein is active on flap and, albeit at low levels,
      on bubble substrates. Like FEN-1, the activity of FEN-1-XPG was stimulated by a
      double-flap substrate containing a 1-nt 3' flap, whereas XPG does not show this
      substrate preference. Although no NER activity was detected in vitro, the FEN-1
      XPG hybrid displays substantial NER activity in vivo. Hence, insertion of the XPG
      spacer region into FEN-1 results in a hybrid protein with biochemical properties
      reminiscent of both nucleases, including partial NER activity.

PMID- 17452370
TI  - Degenerative phenotypes caused by the combined deficiency of murine HIP1 and
      HIP1r are rescued by human HIP1.
AB  - The members of the huntingtin-interacting protein-1 (HIP1) family, HIP1 and HIP1
      related (HIP1r), are multi-domain proteins that interact with inositol lipids,
      clathrin and actin. HIP1 is over-expressed in a variety of cancers and both HIP1
      and HIP1r prolong the half-life of multiple growth factor receptors. To better
      understand the physiological importance of the HIP1 family in vivo, we have
      analyzed a large cohort of double Hip1/Hip1r knockout (DKO) mice. All DKO mice
      were dwarfed, afflicted with severe vertebral defects and died in early
      adulthood. These phenotypes were not observed during early adulthood in the
      single Hip1 or Hip1r knockouts, indicating that HIP1 and HIP1r compensate for one
      another. Despite the ability of HIP1 and HIP1r to modulate growth factor receptor
      levels when over-expressed, studies herein using DKO fibroblasts indicate that
      the HIP1 family is not necessary for endocytosis but is necessary for the
      maintenance of diverse adult tissues in vivo. To test if human HIP1 can function
      similar to mouse HIP1, transgenic mice with 'ubiquitous' expression of the human
      HIP1 cDNA were generated and crossed with DKO mice. Strikingly, the compound
      human HIP1 transgenic DKO mice were completely free from dwarfism and spinal
      defects. This successful rescue demonstrates that the human HIP1 protein shares
      some interchangeable functions with both HIP1 and HIP1r in vivo. In addition, we
      conclude that the degenerative phenotypes seen in the DKO mice are due mainly to
      HIP1 and HIP1r protein deficiency rather than altered expression of neighboring
      genes or disrupted intronic elements.

PMID- 17452371
TI  - Chikungunya Fever.

PMID- 17452372
TI  - Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia
      in parkinsonian rats.
AB  - In patients with Parkinson's disease, the therapeutic efficacy of L-DOPA
      medication is gradually lost over time, and abnormal involuntary movements,
      dyskinesias, gradually emerge as a prominent side-effect in response to
      previously beneficial doses of the drug. Here we show that dyskinesia induced by
      chronic L-DOPA treatment in rats with 6-hydroxydopamine-induced lesions of the
      nigrostriatal dopamine pathway is critically dependent on the integrity and
      function of the serotonergic system. Removal of the serotonin afferents, or
      dampening of serotonin neuron activity by 5-HT1A and 5-HT1B agonist drugs,
      resulted in a near-complete block of the L-DOPA-induced dyskinesias, suggesting
      that dysregulated dopamine release from serotonin terminals is the prime trigger
      of dyskinesia in the rat Parkinson's disease model. In animals with complete
      dopamine lesions, the spared serotonin innervation was unable to sustain the
      therapeutic effect of L-DOPA, suggesting that dopamine released as a 'false
      transmitter' from serotonin terminals is detrimental rather than beneficial. The
      potent synergistic effect of low doses of 5-HT1A and 5-HT1B agonists to suppress
      dyskinesia, without affecting the anti-parkinsonian effect of L-DOPA in presence
      of spared dopamine terminals, suggests an early use of these drugs to counteract
      the development of dyskinesia in Parkinson's disease patients.

PMID- 17452373
TI  - The poetry of Sir Charles Sherrington.

PMID- 17452374
TI  - Sherrington's philosophical writings--a 'zest for life'.
AB  - Sherrington's late writings are often described as dualistic, yet Sherrington was
      deeply uneasy with theories that radically separate mind and brain. His
      questioning, open-minded and historically-informed approach to their relationship
      eschews dogmatic solutions.

PMID- 17452375
TI  - Clinical features of the DOK7 neuromuscular junction synaptopathy.
AB  - Mutations in DOK7 have recently been shown to underlie a recessive congenital
      myasthenic syndrome (CMS) associated with small simplified neuromuscular
      junctions ('synaptopathy') but normal acetylcholine receptor and
      acetylcholinesterase function. We identified DOK7 mutations in 27 patients from
      24 kinships. Mutation 1124_1127dupTGCC was common, present in 20 out of 24
      kinships. All patients were found to have at least one allele with a frameshift
      mutation in DOK7 exon 7, suggesting that loss of function(s) associated with the
      C-terminal region of Dok-7 underlies this disorder. In 15 patients, we were able
      to study the clinical features in detail. Clinical onset was usually
      characterized by difficulty in walking developing after normal motor milestones.
      Proximal muscles were usually more affected than distal, leading to a 'limb
      girdle' pattern of weakness; although ptosis was often present from an early age,
      eye movements were rarely involved. Patients did not show long-term benefit from
      anticholinesterase medication and sometimes worsened, and where tried responded
      to ephedrine. The phenotype can be distinguished from 'limb-girdle' myasthenia
      associated with tubular aggregates, where DOK7 mutations were not detected and
      patients respond to anticholinesterase treatments. CMS due to DOK7 mutations are
      common within our UK cohort and is likely to be under-diagnosed; recognition of
      the phenotype will help clinical diagnosis, targeted genetic screening and
      appropriate management.

PMID- 17452376
TI  - The role of the ventrolateral frontal cortex in inhibitory oculomotor control.
AB  - It has been proposed that the inferior/ventrolateral frontal cortex plays a
      critical role in the inhibitory control of action during cognitive tasks.
      However, the contribution of this region to the control of eye movements has not
      been clearly established. Here, we describe the performance of a group of 23
      frontal lobe damaged patients in an oculomotor rule switching task for which the
      association between a centrally presented visual cue and the direction of a
      saccade could change from trial to trial. A subset of 16 patients also completed
      the standard antisaccade task. Ventrolateral damage was found to be a significant
      predictor of errors in both tasks. Analysis of the rate at which patients
      corrected errors in the rule switching task also revealed an important
      dissociation between left and right hemisphere damaged patients. Whilst patients
      with left ventrolateral damage usually corrected response errors with secondary
      saccades, those with right hemisphere lesions often failed to do so. The results
      suggest that the inferior frontal cortex forms part of a wider frontal network
      mediating inhibitory control over stimulus elicited eye movements. The critical
      role played by the right ventrolateral region in cognitive tasks may arise due to
      an additional functional specialization for the monitoring and updating of task
      rules.

PMID- 17452377
TI  - Etiolation symptoms in sunflower (Helianthus annuus) cotyledons partially covered
      by the pericarp of the achene.
AB  - BACKGROUND AND AIMS: Etiolation symptoms and the greening process are usually
      studied on dark-germinated seedlings and this raises the question--can these
      results be generalized for plants growing under field conditions? This work
      examines various aspects of the plastid differentiation under the covering of the
      achene wall, which often remains attached to the cotyledons of sunflower
      (Helianthus annuus) seedlings grown under light. METHODS: Cotyledons of 7- to 10
      d-old sunflower seedlings grown in the dark and on light were examined. The
      partially covered cotyledons were sectioned into light-exposed, covered and
      transition zones. Pigment contents, 77 K fluorescence spectroscopy, electron
      microscopy and fluorescence imaging, along with fluorescence kinetic methods,
      were used. KEY RESULTS: The light-exposed zone of the partially covered
      cotyledons was similar to cotyledons developed without achene covering. However,
      some of the plastids had prolamellar bodies among the granal thylakoid membranes;
      despite this no protochlorophyllide was detected. The fully covered, yellowish
      sections contained protochlorophyllide forms emitting at 633 and 655 nm and well
      developed prolamellar bodies, similar to those of etiolated cotyledons. In
      addition, reduced amounts of chlorophyll a, chlorophyll b and stacked thylakoid
      membrane pairs were found in this region. The transitional sections showed a
      mixture of the characteristics of the covered and exposed sections. Various, but
      significantly different values of the photosynthetic activity parameters were
      found in each sector of the partially covered cotyledons. CONCLUSIONS: The
      partial covering of the achene wall shades the cotyledon tissues effectively,
      enough to provoke the appearance of etiolation phenomena, i.e. the permanent
      presence of flash-photoactive protochlorophyllide complexes and prolamellar
      bodies (with or without protochlorophyllide), which proves that these phenomena
      may appear under natural illumination conditions.

PMID- 17452378
TI  - Sorghum roots are inefficient in uptake of EDTA-chelated lead.
AB  - BACKGROUND AND AIMS: Ethylene diamine tetraacetic acid (EDTA)-assisted
      phytoremediation has been developed to clean up lead (Pb)-contaminated soil;
      however, the mechanism responsible for the uptake of EDTA-Pb complex is not well
      understood. In this study, the accumulation process of Pb from EDTA-Pb is
      characterized in comparison to ionic Pb [Pb(NO(3))(2)] in sorghum (Sorghum
      bicolor). METHODS: Sorghum seedlings were exposed to a 0.5 mM CaCl(2) (pH 5.0)
      solution containing 0, 1 mM Pb(NO(3))(2) or EDTA-Pb complexes at a molar ratio of
      1:0.5, 1:1, 1:2 and 1:4 (Pb:EDTA). The root elongation of sorghum at different
      ratios of Pb:EDTA was measured. Xylem sap was collected after the stem was
      severed at different times. The concentration of Pb in the shoots and roots were
      determined by an atomic absorption spectrometer. In addition, the roots were
      stained with Fluostain I for observation of the root structure. KEY RESULTS: Lead
      accumulation in the shoots of the plants exposed to EDTA-Pb at 1:1 ratio was only
      one-fifth of that exposed to ionic Pb at the same concentration. Lead
      accumulation decreased when transpiration was suppressed. The concentration of Pb
      in the xylem sap from the EDTA-Pb-treated plants was about 1/25,000 of that in
      the external solution. Root elongation was severely inhibited by ionic Pb, but
      not by EDTA-Pb at a 1:1 ratio. Root staining showed that a physiological barrier
      was damaged in the roots exposed to ionic Pb, but not in the roots exposed to
      EDTA-Pb. CONCLUSIONS: All these results suggest that sorghum roots are
      inefficient in uptake of EDTA-chelated Pb and that enhanced Pb accumulation from
      ionic Pb was attributed to the damaged structure of the roots.

PMID- 17452379
TI  - Differential responses of lichen symbionts to enhanced nitrogen and phosphorus
      availability: an experiment with Cladina stellaris.
AB  - BACKGROUND AND AIMS: Lichens can be both nitrogen- (N) and phosphorous- (P)
      limited and thus may be susceptible to nutrient enrichment. Nutrient enrichment
      with N and P may have differing impacts on the lichen structure because of
      different physiological responses of fungal and algal partners to these
      nutrients. The hypothesis was tested that the differential responses of lichen
      symbionts to enhanced availability of N and P is reflected in the lichen thallus
      structure and the wall-to-wall interface between the algal and fungal cells.
      METHODS: Lichen cushions of Cladonia stellaris were treated with one P and two N
      concentrations alone and in combination that yielded total depositions of approx.
      300 (moderate) and 1000 (high) mg N m(-2) and 100 (high) mg P m(-2) over an
      experiment lasting 14 weeks. The effects of N and P inputs on the relative
      volumes of fungal and algal cell in the medullary tissue and on the thallus
      structure were studied using light microscopy. The interface between algal and
      fungal cell walls was examined using transmission electron microscopy. KEY
      RESULTS: The influence of excess P on the lichen thallus structure was stronger
      than that of additional N. Addition of P reduced the N : P ratio in podetia, the
      proportion of the medullary layer volume occupied by the algal cells, the thallus
      volume occupied by the internal lumen, and the algal cell-wall area covered by
      fungal hyphae. CONCLUSIONS: Ecologically realistic changes in the availability of
      key macronutrients can alter the growth of symbionts. Reduction in the proportion
      of photobiont cells indicates that the application of P either stimulates fungal
      hyphal growth in the medullary tissue or impairs the cell division of the algal
      cells. The results suggest that both the N and P availability and thallus N : P
      ratio affect the growth rates of lichen symbionts.

PMID- 17452380
TI  - Construction costs and physico-chemical properties of the assimilatory organs of
      Nepenthes species in Northern Borneo.
AB  - BACKGROUND AND AIMS: Species of the Nepenthaceae family are under-represented in
      studies of leaf traits and the consequent view of mineral nutrition and
      limitation in carnivorous plants. This study is aimed to complement existing data
      on leaf traits of carnivorous plants. METHODS: Physico-chemical properties,
      including construction costs (CC), of the assimilatory organs (leaf and pitcher)
      of a guild of lowland Nepenthes species inhabiting heath and/or peat swamp
      forests of Brunei, Northern Borneo were determined. KEY RESULTS: Stoichiometry
      analyses indicate that Nepenthes species are nitrogen limited. Most traits vary
      appreciably across species, but greater variations exist between the assimilatory
      organs. Organ mass per unit area, dry matter tissue concentration (density),
      nitrogen (N), phosphorus (P), carbon, heat of combustion (H(c)) and CC values
      were higher in the leaf relative to the pitcher, while organ thickness, potassium
      (K) and ash showed the opposite trend. Cross-species correlations indicate that
      joint rather than individual consideration of the leaf and the pitcher give
      better predictive relationships between variables, signalling tight coupling and
      functional interdependence of the two assimilatory organs. Across species, mass
      based CC did not vary with N or P, but increases significantly with tissue
      density, carbon and H(c), and decreases with K and ash contents. Area-based CC
      gave the same trends (though weaker in strength) in addition to a significant
      positive correlation with tissue mass per unit area. CONCLUSIONS: The lower CC
      value for the pitcher is in agreement with the concept of low marginal cost for
      carnivory relative to conventional autotrophy. The poor explanatory power of N, P
      or N : P ratio with CC suggests that factors other than production of expensive
      photosynthetic machinery (which calls for a high N input), including
      concentrations of lignin, wax/lipids or osmoregulatory ions like K(+), may give a
      better explanation of the CC variation across Nepenthes species.

PMID- 17452381
TI  - Development and seed number in indeterminate soybean as affected by timing and
      duration of exposure to long photoperiods after flowering.
AB  - BACKGROUND AND AIMS: Long photoperiods from flowering to maturity have been found
      to delay reproductive development in soybean (Glycine max) and to increase the
      number of seeds per unit land area. This study was aimed to evaluate whether
      sensitivity to photoperiod after flowering (a) is quantitatively related to the
      length of exposure to long days and (b) persists throughout the whole pod-setting
      period. It was also evaluated whether seed number was related to changes in the
      duration of post-flowering phenophases. METHODS: Two field experiments were
      conducted with an indeterminate cultivar of soybean of maturity group V. In expt
      1, photoperiods 2 h longer than natural daylength were applied during different
      numbers of days from the beginning pod stage (R3) onwards, while in expt 2 these
      photoperiod extensions were imposed during 9 consecutive days starting at
      different times between R3 and R6 (full seed) stages. KEY RESULTS: There was a
      quantitative response of development to the number of cycles with a long
      photoperiod. The exposure to long photoperiods from R3 to R5 (beginning of seed
      growth) increased the duration of R3-R6 regardless of the timing of exposure. The
      stages of development comprised in the R3-R6 phase were delayed by current as
      well as by previous exposure to long days. A positive relationship was found
      between seed number and the duration of R3-R6, irrespective of the timing and
      length of exposure to the long photoperiod. CONCLUSIONS: Sensitivity to
      photoperiod remained high during the reproductive period and was highly and
      positively coupled with the processes of generation of yield.

PMID- 17452382
TI  - A comparative study of germination ecology of four Papaver taxa.
AB  - BACKGROUND AND AIMS: Comparative studies of closely related taxa can increase
      understanding of adaptations and changes in seed dormancy and germination
      preferences in an evolutionary perspective. For such studies, a method to
      describe and compare the performance of taxa in a general way is needed. The
      germination ecology of four Papaver taxa was studied with the aim of describing
      and comparing their responses to different seasonal temperature regimes. METHODS:
      Germination of Papaver argemone, P. rhoeas, P. dubium ssp. dubium and P. dubium
      ssp. lecoqii was investigated in three different artificial climates over 2.5
      years. Seeds were collected in southern Sweden, and samples from different
      populations were used as replicates of taxa. KEY RESULTS: Despite substantial
      intra-taxa variation, there were clear taxon-specific responses. Most germination
      occurred in the warmest climate. In general, the warmer the climate the more
      germination occurred in autumn instead of spring. Papaver argemone,
      phylogenetically most distant from the other taxa, was, in contrast to the
      others, restricted to germinating only at lower temperatures. CONCLUSIONS: Seed
      dormancy and germination may be described by dormancy pattern, germination
      preferences and dormancy strength. The general dormancy pattern was a common
      feature for these taxa and therefore probably an evolutionary conservative
      character. Germination preferences varied between taxa, resulting in different
      temperature optima and intervals for germination, and dormancy strength was to
      some extent taxon-specific, but highly variable. The dormancy pattern explained
      how the taxa can perform as winter annuals in warmer climates, but mainly as
      summer annuals in colder climates. Hence, there is no need to interpret the
      within-taxon temporal differences in seedling emergence as local adaptations. In
      the field, an entire seed cohort will not germinate during a single season.
      Instead, emergence will be distributed over several seasons, regardless of local
      climate, weather and soil cultivation methods.

PMID- 17452383
TI  - Relationship between the Al resistance of grasses and their adaptation to an
      infertile habitat.
AB  - BACKGROUND AND AIMS: Original data on Al resistance, relative growth rate and
      leaf traits of five European grasses as well as literature data on Al resistance,
      habitat preference and traits of grasses were considered to determine whether (a)
      Al resistance is correlated to a growth conservative strategy and (b) species
      occurrence could be useful to assess Al toxicity in meadows on acid soils.
      METHODS: The Al resistance of 15 species was represented by the Al activity in
      nutrient solution that resulted in a 50 % decrease in root length, [Al(3+)](50),
      or, for published values, in root or plant biomass. The correlations between Al
      resistance and acidity or nitrogen indices and the correlation between Al
      resistance and selected traits (relative growth rate, leaf dry matter content,
      specific leaf area and leaf thickness) were calculated. Principal component
      analysis was used for the characterization of the relationships between Al
      resistance and measured traits. KEY RESULTS: The [Al(3+)](50) values of the
      resistant species Molinia caerulea and Sieglingia decumbens were 13 and 26 microm
      [Al(3+)](50), respectively. The known Al resistance of 15 species that were
      mainly of the intermediate strategy competitor-stress tolerator-ruderal (C-S-R)
      type and of the S type was correlated with Ellenberg's nitrogen and acidity
      indices. For the whole set of species, the correlation between Al resistance and
      traits was not significant. CONCLUSION: The Al resistance of the C-S-R species
      was variable and independent of their traits. S-type species, adapted to acid
      soils and with traits of conservative strategy, displayed Al resistance. The
      large difference in Al resistance between grasses may help assess Al soil
      toxicity by using the abundance of grasses.

PMID- 17452384
TI  - Comparative plant ecology as a tool for integrating across scales.

PMID- 17452385
TI  - Self-assembling plants and integration across ecological scales.
AB  - BACKGROUND AND AIMS: Although individual plants exhibit much complex behaviour in
      response to environmental stimuli, they appear to do so without any identifiable
      centres of organization. We review a special class of model with the aim of
      testing whether plants can effectively be self-assembling, modular-driven
      organisms, in the sense that whole-plant organization and behaviour emerges
      solely from the interactions of much smaller structural elements. We also review
      evidence that still higher-level behaviour, at the population and community
      levels of organization, can emerge from this same source. METHODS: In previous
      work we devised a special cellular automaton (CA) model of plant growth. This
      comprises a section depicting a two-dimensional plant in its above- and below
      ground environments. The whole plant is represented by branching structures made
      up from identical 'modules'. The activity of these modules is driven by
      morphological, physiological and reproductive rulesets derived from comparative
      plant ecology, a feature which lends itself to experimentation at several
      ecological scales. KEY RESULTS: From real experiments using virtual plants we
      show that the model can reproduce a very wide range of whole-plant-, population-
      and community-level behaviour. All of these properties emerge successfully from a
      ruleset acting only at the level of the CA module. CONCLUSIONS: The CA model can,
      with advantage, be driven by C-S-R plant strategy theory. As this theory can
      ascribe a functional classification to any temperate angiosperm on the basis of a
      few simple tests, any community of such plants can be redescribed in terms of its
      'functional signature' and the net environment that it experiences. To a valuable
      first approximation, therefore, a C-S-R version of the CA model can simulate the
      most essential properties both of natural vegetation and of its environment. We
      have thus achieved a position from which we can test a plethora of high-level
      community processes, such as diversity, vulnerability, resistance, resilience,
      stability, and habitat-community heterogeneity--processes which, if investigated
      on the scales truly required for a full understanding, would fall beyond the
      practical scope of even the largest real-life investigation.

PMID- 17452386
TI  - Commentary: Growing up optimally in societies undergoing the nutritional
      transition, public health and research challenges.

PMID- 17452387
TI  - Commentary: the ubiquity of prostate cancer: echoes of the past, implications for
      the present: "what has been will be again, what has been done will be done again;
      there is nothing new under the sun." ECCLESIASTES 1:9.

PMID- 17452389
TI  - Use of administrative data or clinical databases as predictors of risk of death
      in hospital: comparison of models.
AB  - OBJECTIVE: To compare risk prediction models for death in hospital based on an
      administrative database with published results based on data derived from three
      national clinical databases: the national cardiac surgical database, the national
      vascular database and the colorectal cancer study. DESIGN: Analysis of inpatient
      hospital episode statistics. Predictive model developed using multiple logistic
      regression. SETTING: NHS hospital trusts in England. PATIENTS: All patients
      admitted to an NHS hospital within England for isolated coronary artery bypass
      graft (CABG), repair of abdominal aortic aneurysm, and colorectal excision for
      cancer from 1996-7 to 2003-4. MAIN OUTCOME MEASURES: Deaths in hospital.
      Performance of models assessed with receiver operating characteristic (ROC) curve
      scores measuring discrimination (<0.7=poor, 0.7-0.8=reasonable, >0.8=good) and
      both Hosmer-Lemeshow statistics and standardised residuals measuring goodness of
      fit. RESULTS: During the study period 152 523 cases of isolated CABG with 3247
      deaths in hospital (2.1%), 12 781 repairs of ruptured abdominal aortic aneurysm
      (5987 deaths, 46.8%), 31 705 repairs of unruptured abdominal aortic aneurysm
      (3246 deaths, 10.2%), and 144,370 colorectal resections for cancer (10,424
      deaths, 7.2%) were recorded. The power of the complex predictive model was
      comparable with that of models based on clinical datasets with ROC curve scores
      of 0.77 (v 0.78 from clinical database) for isolated CABG, 0.66 (v 0.65) and 0.74
      (v 0.70) for repairs of ruptured and unruptured abdominal aortic aneurysm,
      respectively, and 0.80 (v 0.78) for colorectal excision for cancer. Calibration
      plots generally showed good agreement between observed and predicted mortality.
      CONCLUSIONS: Routinely collected administrative data can be used to predict risk
      with similar discrimination to clinical databases. The creative use of such data
      to adjust for case mix would be useful for monitoring healthcare performance and
      could usefully complement clinical databases. Further work on other procedures
      and diagnoses could result in a suite of models for performance adjusted for case
      mix for a range of specialties and procedures.

PMID- 17452390
TI  - Effectiveness of visits from community pharmacists for patients with heart
      failure: HeartMed randomised controlled trial.
AB  - OBJECTIVE: To test whether a drug review and symptom self management and
      lifestyle advice intervention by community pharmacists could reduce hospital
      admissions or mortality in heart failure patients. DESIGN: Randomised controlled
      trial. SETTING: Home based intervention in heart failure patients. PARTICIPANTS:
      293 patients diagnosed with heart failure were included (149 intervention, 144
      control) after an emergency admission. INTERVENTION: Two home visits by one of 17
      community pharmacists within two and eight weeks of discharge. Pharmacists
      reviewed drugs and gave symptom self management and lifestyle advice. Controls
      received usual care. MAIN OUTCOME MEASURES: The primary outcome was total
      hospital readmissions at six months. Secondary outcomes included mortality and
      quality of life (Minnesota living with heart failure questionnaire and EQ-5D).
      RESULTS: Primary outcome data were available for 291 participants (99%). 136
      (91%) intervention patients received one or two visits. 134 admissions occurred
      in the intervention group compared with 112 in the control group (rate
      ratio=1.15, 95% confidence interval 0.89 to 1.48; P=0.28, Poisson model). 30
      intervention patients died compared with 24 controls (hazard ratio=1.18, 0.69 to
      2.03; P=0.54). Although EQ-5D scores favoured the intervention group, Minnesota
      living with heart failure questionnaire scores favoured controls; neither
      difference was statistically significant. CONCLUSION: This community pharmacist
      intervention did not lead to reductions in hospital admissions in contrast to
      those found in trials of specialist nurse led interventions in heart failure.
      Given that heart failure accounts for 5% of hospital admissions, these results
      present a problem for policy makers who are faced with a shortage of specialist
      provision and have hoped that skilled community pharmacists could produce the
      same benefits. TRIAL REGISTRATION NUMBER: ISRCTN59427925.

PMID- 17452391
TI  - European Union: the seventh Framework Programme resuscitates public health
      research.

PMID- 17452392
TI  - Undergraduate training in geriatric medicine: getting it right.

PMID- 17452393
TI  - Comparison of the frequency of defective sperm-zona pellucida (ZP) binding and
      the ZP-induced acrosome reaction between subfertile men with normal and abnormal
      semen.
AB  - BACKGROUND: The aim of this study was to compare the frequency of defective sperm
      zona pellucida (ZP) binding (DSZPB) and defective ZP-induced acrosome reaction
      (DZPIAR) in subfertile men (i.e. male partners of infertile couples) with normal
      and abnormal semen analyses. METHODS: A total of 1030 subfertile men with normal
      semen analysis (n=255), oligozoospermia (count<20x10(6)/ml, n=136), severe
      teratozoospermia (strict normal morphology<or=5%, n=294) and mild-moderate
      teratozoospermia (morphology 6-14%, n=345) were studied. Unfertilized oocytes
      from clinical in vitro fertilization/intracytoplasmic sperm injection were used
      for sperm-ZP interaction tests. After 2 h incubation of motile sperm with four
      oocytes, sperm tightly bound to the ZP, and the AR of ZP-bound sperm (ZPIAR) were
      assessed. An average of <40 sperm bound/ZP and <16% ZPIAR were used for diagnosis
      of DSZPB or DZPIAR. RESULTS: For the groups of men with normal semen or mild
      moderate teratozoospermia, severe teratozoospermia and oligozoospermia, the
      frequencies of DSZPB were: 13, 21, 29 and 28%, respectively, and in those normal
      SZPB, DZPIAR were 27, 36, 56 and 68%, respectively. Overall DSZPB and ZPIAR were
      36, 49, 68 and 77% for the four groups, respectively. The highest frequencies of
      defective sperm-ZP interaction were in the oligozoospermia and severe
      teratozoospermia groups. In the normal and teratozoospermia groups, subjects with
      a relatively low sperm concentration (20-60x10(6)/ml) had a significantly higher
      frequency of DZPIAR. CONCLUSION: Defective sperm-ZP interaction is a major
      mechanism of male infertility. DZPIAR is more frequent than DSZPB in subfertile
      men with either normal or abnormal semen, suggesting that sequential sperm-ZP
      interaction tests are essential to detect these sperm defects.

PMID- 17452394
TI  - Endometriosis is associated with a decreased risk of pre-eclampsia.
AB  - BACKGROUND: We postulated that impaired endometrial differentiation in women with
      pelvic endometriosis predisposes for pre-eclampsia. METHODS: A retrospective case
      control study set at the University of Ghent IVF centre. The incidence of pre
      eclampsia and pregnancy-induced hypertension (PIH) following the clinical and/or
      laparoscopic diagnosis of endometriosis-associated infertility (case group; n =
      245 pregnancies) was compared with the incidence of these obstetric complications
      in pregnancies following treatment for male-factor infertility (control group; n
      = 274 pregnancies). Pregnancy data were obtained by searching electronic
      databases and postal questionnaires. The case and control groups were matched for
      age, parity and multiple pregnancies. RESULTS: The incidence of pre-eclampsia was
      significantly lower in the case group (0.8%) when compared with control group
      (5.8%) (P = 0.002; odds ratio (OR) = 7.5, 95% confidence interval (CI): 1.7
      33.3). Analysis of obstetric outcome in the subgroup of patients with
      laparoscopic data confirmed the lower risk of pre-eclampsia in the case (1.2%)
      versus control (7.4%) groups (P = 0.032; OR = 6.6, 95% CI: 1.2-37). PIH occurred
      in 3.5% and 8.7% of case and control pregnancies, respectively (P = 0.018; OR =
      2.6, 95% CI: 1.2-6.0). The odds of developing pre-eclampsia were 5.67 times
      higher in the control group than in pregnancies following endometriosis
      associated infertility. In multiple pregnancies, the odds of developing pre
      eclampsia increased 1.93 times per additional child, with or without
      endometriosis. CONCLUSIONS: We found no evidence that endometriosis predisposes
      for pre-eclampsia. Instead, the risk of hypertensive disorder in pregnancy is
      significantly reduced in women with endometriosis-associated infertility.

PMID- 17452395
TI  - Spontaneous pregnancy and normal delivery after repeated autologous bone marrow
      transplantation and GnRH agonist treatment.

PMID- 17452396
TI  - Spontaneous adenomyosis in the chimpanzee (Pan troglodytes): a first report and
      review of the primate literature: case report.
AB  - Adenomyosis is a non-neoplastic condition characterized by the presence of
      ectopic endometrium in the myometrium with hyperplasia of adjacent smooth muscle.
      Common symptoms in women include debilitating pelvic pain and abnormal uterine
      bleeding, and the condition has been paradoxically associated with both
      multiparity and subfertility. Adenomyosis spontaneously occurs in humans and some
      non-human primates, including the baboon and macaque, where it has been
      associated with primary infertility and the presence of endometriosis. No cases
      of adenomyosis have been previously reported in Pongidae such as gorilla,
      orangutan or chimpanzee. We here describe two cases of naturally occurring
      adenomyosis in the chimpanzee (Pan troglodytes) and briefly review the literature
      regarding the presence of adenomyosis in non-human primate species.

PMID- 17452397
TI  - Xenotransplantation of testicular tissue into nude mice can be used for detecting
      leukemic cell contamination.
AB  - BACKGROUND: Xeno-grafting of testicular tissue may allow viable gamete
      maturation. This would be beneficial for prepubertal cancer patients in that it
      may allow restoration of fertility without the risk of a cancer relapse. However
      it is unknown whether cancer cells in the testicular graft can transmit the
      malignancy into the host animal and also if gametes can be retrieved from
      testicular grafts that are contaminated with malignant cells. METHODS: Rat T-cell
      leukemia was employed as the source of leukemic lymphoblasts and testicular
      tissue. This was injected i.p. (lymphoblasts) or grafted s.c. (fresh or
      cryopreserved testicular tissue) into the back skin of intact nude mice. To
      simulate clinical autografting, testicular tissue was also transplanted into
      healthy piebald variegated (PVG) rats. RESULTS: 50-70% of the mice, receiving 200
      or 6000 leukemic lymphoblasts, developed terminal leukemia. All mice, grafted
      with either fresh or cryopreserved testicular tissue from leukemic donor,
      developed generalized leukemia and/or local tumors. All syngenic PVG rats,
      treated in the same manner, died of generalized leukemia. In all of the retrieved
      leukemic grafts, rat spermatogenesis was destroyed and only leukemic infiltration
      was detected. CONCLUSIONS: Grafting testicular tissue contaminated with leukemic
      cells led to tumor growth at the injection site without potential to
      differentiate germline stem cells into gametes. Xenografting could provide a
      novel functional strategy for simultaneous detection of malignant cell
      contamination and spermatogonial potential in testicular xenografts collected for
      fertility preservation.

PMID- 17452399
TI  - Prevention of adhesions in gynaecological endoscopy.
AB  - Adhesions resulting from gynaecological endoscopic procedures are a major
      clinical, social and economic concern, as they may result in pelvic pain,
      infertility, bowel obstruction and additional surgery to resolve such adhesion
      related complications. Although the minimally invasive endoscopic approach has
      been shown to be less adhesiogenic than traditional surgery, at least with regard
      to selected procedures, it does not totally eliminate the problem. Consequently,
      many attempts have been made to further reduce adhesion formation and reformation
      following endoscopic procedures, and a wide variety of strategies, including
      surgical techniques, pharmacological agents and mechanical barriers have been
      advocated to address this issue. The present review clearly indicates that there
      is no single modality proven to be unequivocally effective in preventing post
      operative adhesion formation either for laparoscopic or for hysteroscopic
      surgery. Furthermore, the available adhesion-reducing substances are rather
      expensive. Since excellent surgical technique alone seems insufficient, further
      research is needed on an adjunctive therapy for the prevention and/or reduction
      of adhesion formation following gynaecological endoscopic procedures.

PMID- 17452400
TI  - Analysis of T-wave morphology from the 12-lead electrocardiogram for prediction
      of long-term prognosis in patients initiating haemodialysis.
AB  - BACKGROUND: Cardiovascular disease remains the most common cause of death in end
      stage renal disease (ESRD). Recently, novel descriptors of T-wave morphology have
      been suggested as measures of repolarization heterogeneity and adverse prognosis
      in non-uraemic populations. However, whether these T-wave descriptors provide
      prognostic information in uraemic populations has not been examined. The present
      study aimed to determine the prognostic value of novel T-wave morphology
      variables in predicting total, cardiovascular and arrhythmia-related mortality in
      ESRD patients initiating haemodialysis. METHODS: The study was a retrospective
      cohort of adult ESRD patients starting haemodialysis between 1998 and 2005;
      follow-up was until September 2006. A total of 325 patients were studied. Novel
      ECG variables characterizing repolarization and the T-wave loop were analysed.
      RESULTS: Of 325 patients with technically analysable data, 154 (47.4%) died after
      a mean follow-up of 25.5+/-21.7 months. Direct comparison between cardiovascular
      death and non-cardiovascular death patients showed that the relative T-wave
      residuum (TWR) predicted cardiovascular mortality (0.20+/-0.21% vs 0.24+/-0.17%,
      P=0.005). In Cox modeling, relative TWR was an independent predictor of
      cardiovascular [relative risk (RR)=1.86; P=0.013] and arrhythmia-related
      mortality (RR=2.102; P=0.012). CONCLUSIONS: The heterogeneity of myocardial
      repolarization, measured by the relative T-wave residuum in the ECG, appears to
      be an independent predictor of cardiovascular and arrhythmia-related mortality in
      patients initiating haemodialysis.

PMID- 17452401
TI  - Removal of BNP and inflammatory cytokines by haemodiafiltration in refractory
      heart failure.

PMID- 17452402
TI  - Stability of lipids on peritoneal dialysis in a patient with familial LCAT
      deficiency.

PMID- 17452403
TI  - Renal osteodystrophy manifesting as localized enlargement of the jaw.

PMID- 17452404
TI  - Combined effects of moderately elevated blood glucose and locally produced TGF
      beta1 on glomerular morphology and renal collagen production.
AB  - BACKGROUND: There is a correlation between renal graft rejection and blood
      glucose (BG) levels. Furthermore, diabetic patients may develop non-diabetic
      renal diseases, which in some circumstances progress rapidly. Since transforming
      growth factor-beta1 (TGF-beta) levels are elevated in many renal diseases, the
      accelerated progression may be due to interactions between glucose and locally
      produced TGF-beta1. Therefore, we investigated the effect of mild hyperglycaemia
      on glomerular morphology and collagen production in TGF-beta1 transgenic mice.
      METHODS: To achieve BG concentrations of approximately 15 mmol/l in TGF-beta1
      transgenic and non-transgenic mice, we used multiple streptozotocin (STZ)
      injections, and after 8 weeks, we measured the changes in glomerular morphology
      and total collagen content. We also analysed extracellular matrix (ECM) and
      protease mRNA levels using real-time polymerase chain reaction (PCR) and
      phosphorylated extracellular signal-regulated kinase 1/2 (pERK) expression by
      immunohistochemistry. RESULTS: Mild hyperglycaemia alone had no effect on
      glomerular structure or ECM deposition. Over-expression of TGF-beta1 increased
      basement membrane thickness (BMT) and the mesangial volume fraction. Furthermore,
      it augmented ECM, Matrix metalloproteinase-2 (MMP), MMP-9, plasminogen activator
      inhibitor-1 (PAI) and tissue inhibitor of metalloproteinase-1 (TIMP) gene
      expression and pERK1/2 immunostaining. Elevated BG in combination with TGF-beta1
      resulted in enlargement of glomerular volume, total mesangial volume and renal
      collagen content. Moreover, high BG exaggerated TGF-beta1-induced changes in the
      BMT, MMP-2 and TIMP-1 expression and pERK1/2 staining. CONCLUSION: Even moderate
      elevations in BG accelerate the progression of those kidney diseases in which TGF
      beta1 is involved. This emphasizes the importance of strict BG control in renal
      transplant patients and diabetic patients with renal malfunctions unrelated to
      diabetes.

PMID- 17452405
TI  - T-cell homing receptor expression in IgA nephropathy.
AB  - BACKGROUND: IgA nephropathy (IgAN) is characterized by mesangial deposition of
      polymeric IgA (pIgA). In IgAN, mucosal pIgA production is reduced while systemic
      production is increased, making the latter the likely source of mesangial pIgA,
      and suggesting a displacement of pIgA-producing cells from mucosal to systemic
      sites. Upon activation, lymphocytes migrate through the circulation up-regulating
      homing receptors (HR) which direct their return to appropriate effector
      locations. We investigated the HR expression of T-cell subsets in IgAN, healthy
      adults and membranous nephropathy (MN). METHODS: Peripheral blood cells were
      labelled for CD3, CD4 and CD8, and for L-selectin (naive cells), integrin
      alpha4beta1 (systemically homing cells) and integrin alpha4beta7 (mucosally
      homing cells) and analysed by flow immunocytometry. RESULTS: In IgAN, CD3 T cells
      displayed reduced L-selectin and increased alpha4beta1hi expression, with no
      difference in alpha4beta7. No abnormality of T-cell HR expression was found in
      MN. Both IgAN and healthy adults maintained their patterns of T-cell HR
      expression when studied again at a later time point, and the changes in IgAN were
      entirely accounted for by the CD4 T-cell subset with CD8 HR expression being
      normal. CONCLUSIONS: The consistently reduced L-selectin expression by CD4 T
      cells indicates increased activation of this subset in IgAN. These activated
      cells express alpha4beta1 rather than alpha4beta7, and therefore home to systemic
      effector sites. CD4 T cells regulate antibody production, including IgA. As pIgA
      is overproduced in systemic sites in IgAN, we hypothesize that these activated
      systemic homing CD4 T cells may direct the aberrant systemic pIgA production
      observed in IgAN.

PMID- 17452406
TI  - Long-term outcome of third kidney transplants.
AB  - Third renal transplants are historically associated with a poor prognosis. An
      analysis was undertaken to assess long-term outcomes of third grafts and identify
      variables associated with long-term graft survival. Fifty-six third grafts
      performed between 1974 and 2005 were compared to control groups of 1965 primary
      and 301 second grafts performed during the same period. Kaplan-Meier analysis
      showed a graft survival rate of 91%, 72% and 58% at 1, 5 and 10 years,
      respectively, for third transplants. Graft and patient survival of third grafts
      were similar to those of first and second transplants. Univariate analysis showed
      that HLA-A mismatch (P<0.01), absence of calcineurin inhibitor as part of the
      initial immuno-suppressive regimen (P=0.03), acute rejection (P=0.04) and
      transplantation prior to 1990 (P=0.04) were associated with a poor third graft
      survival. Multivariate analysis indicated that 1 year serum creatinine (HR=1.02,
      P=0.001), 1 year proteinuria (HR=1.84, P=0.01), absence of calcineurin inhibitor
      (HR=10.6, P=0.01) and complete HLA-A match (HR=0.13, P=0.03) were independently
      associated with graft loss. Although third graft recipients have a range of risk
      factors previously associated with poor patient and graft outcome, that remain
      difficult to delineate in a retrospective analysis due to the possible selection
      of the third transplant candidates, these results suggest that third graft and
      patient survival rates could be similar to those of first and second transplants.

PMID- 17452407
TI  - Association between oestrogen receptor alpha gene polymorphism and mortality in
      female end-stage renal disease patients.
AB  - BACKGROUND: In the general population, genetic variations in the oestrogen
      receptor alpha (ERalpha) gene may influence lipid abnormalities, cardiovascular
      disease (CVD), and mortality, but this has not previously been studied in end
      stage renal disease (ESRD) patients. METHODS: A total of 227 ESRD (141 men and 86
      women) patients starting renal replacement therapy (RRT) were genotyped for three
      ERalpha gene polymorphisms (Ser10Ser, PvuII and XbaI) and the associations
      between these polymorphisms and clinical and laboratory parameters and survival
      were analysed. Patients were followed for a median period of 55 months (range 1
      126 months). RESULTS: The PvuII and XbaI polymorphisms were not associated with
      any of the clinical parameters. The ERalpha Ser10Ser CC genotype was present in
      24 (28%) of the female and in 37 (26%) of the male patients. When comparing the
      CC genotype with the CT and TT genotypes, there were significant differences in
      lipid levels and inflammatory marker levels, especially in female patients. In
      female patients, the CC genotype was associated with lower prevalence of protein
      energy wasting (PEW) (17.4% vs 43.1%; P=0.03), lower median serum triglyceride
      (1.7 vs 2.1 mmol/l; P=0.001), higher median serum albumin (34.0 vs 32.5 g/l;
      P=0.03) and lower median high sensitivity-CRP (hsCRP) (2.2 vs 5.5 mg/l; P=0.03)
      levels compared with the CT plus TT genotypes. In male patients only HDL
      cholesterol and ApoA levels were associated with this polymorphism. Whereas this
      polymorphism did not influence survival in males, the mortality was lower in
      female patients with the CC genotype (Kaplan-Meier; Log-rank 2.2, P=0.02).
      Moreover, female patients with the CT plus TT genotypes had a borderline
      significant increased relative risk (Cox hazard model; 6.6, 95% CI: 0.87-49.9
      P=0.06) of death as compared with those with the CC genotype, even after
      adjustment for age and prevalence of CVD. CONCLUSIONS: Female, but not male ESRD
      patients with the ERalpha Ser10Ser CC genotype had lower prevalence of PEW, lower
      serum triglyceride, higher serum albumin and lower hsCRP levels. As this genotype
      was associated with a significantly decreased risk of all-cause death during the
      initial years of RRT, its protective properties need further study.

PMID- 17452408
TI  - Chronic kidney disease and mortality and morbidity among patients with
      established cardiovascular disease: a West of Ireland community-based cohort
      study.
AB  - BACKGROUND: The importance of chronic kidney disease as an independent risk
      factor for morbidity and mortality in patients with cardiovascular disease in the
      community is not widely recognized. METHODS: A retrospective cohort study based
      in the West of Ireland followed a randomized practice-based sample of patients
      with cardiovascular disease. A database of 1609 patients with established
      cardiovascular disease was established in 2000. This was generated from a
      randomized sample of 35 general practices in the West of Ireland. The primary
      endpoint was a cardiovascular composite endpoint, which included death from a
      cardiovascular cause or any of the cardiovascular events of myocardial infarction
      (MI), heart failure, peripheral vascular disease and stroke. The secondary
      endpoint was death from any cause. RESULTS: Of the original community-based
      cohort of 1609 patients with cardiovascular disease, 1272 (79%) had one or more
      serum creatinine measurements during the study period and 31 (1.9%) patients were
      lost to follow-up. Median follow-up was 2.90 years (SD 1.47) and the risk of the
      cardiovascular composite endpoint (total of 219 events) was significantly
      increased in those patients with reduced estimated glomerular filtration rate
      (GFR) [log rank (Mantel-Cox) 26.74, P<0.001] as was the risk of death from any
      cause (total of 214 deaths) [Log Rank (Mantel-Cox) 56.97, P<0.001]. On the basis
      of the proportional hazards model, while adjusting for other significant
      covariates, reduced estimated GFR was associated with a significant increase in
      risk of the primary and secondary outcomes (P<0.01). For every 10 ml decrement in
      estimated GFR there was a corresponding 20% increase in hazard of the
      cardiovascular composite endpoint and a 33% increase in hazard of death from any
      cause. CONCLUSIONS: Estimated GFR appears to discriminate prognosis between
      patients with established cardiovascular disease. These results emphasise the
      importance of recognising chronic kidney disease as a significant risk factor in
      patients with cardiovascular disease in the community.

PMID- 17452409
TI  - Accelerated increase of arteriovenous fistula use in haemodialysis centres:
      results of the multicentre CIMINO initiative.
AB  - BACKGROUND: In the Netherlands, arteriovenous fistulas (AVFs) are used in 60-65%
      of the haemodialysis patients and this compares poorly with the European average.
      A multicentre guidelines implementation programme, CIMINO, was initiated aiming
      at increasing the use of AVFs. METHODS: Physicians and dialysis staff in 11
      participating centres (N=1092 vascular accesses) were strongly and repeatedly
      advised to adhere to current guidelines with extra attention for pre-operative
      duplex examination and salvaging of failing and failed fistulae. Specially
      appointed access nurses prospectively registered all created vascular accesses
      using an internet-linked database. In 22 other centres (N=1566 accesses), the
      CIMINO programme was not offered and they were considered the control group.
      RESULTS: On 1 January 2006, average follow-up time of the CIMINO group and the
      control group were 13.3 months and 34.1 months, respectively. A total of 598 new
      vascular accesses (77% AVFs) were created in the CIMINO group. Prevalent AVF use
      increased from 58.5% (range: 31-79%) to 62.7% (range: 45-83%) in the CIMINO group
      and from 65.5% (range: 31-91%) to 67.3% (range: 42-91%) in the control group. The
      increase in AVF use per year was significantly quicker than in the control group
      (P<0.05). Use of untunnelled catheters decreased whereas that of tunnelled
      catheters increased. CONCLUSIONS: This initiative shows that a multicentre
      guidelines implementation programme results in an accelerated increase of AVF use
      in comparison with a time control group. These data suggest that the choice of
      access placement depends predominantly on centre-specific factors.

PMID- 17452410
TI  - Impact of haemoglobin concentration and chronic kidney disease in patients with
      coronary heart disease undergoing percutaneous coronary interventions.
AB  - BACKGROUND: A few recent studies suggested that anaemia has a marked impact on
      the survival of patients with coronary heart disease (CHD). However, all of these
      analyses did not take into consideration that chronic kidney disease (CKD) plays
      an important role in erythropoiesis and anaemia. Therefore, we assessed in this
      study whether anaemia is an independent predictor of mortality or if its impact
      was confounded by CKD, which is known to have itself a marked impact on outcomes
      of patients with CHD. METHODS: In a retrospective cohort study, we analysed 709
      patients with symptomatic and significant CHD who underwent percutaneous coronary
      interventions. Patients were classified as anaemic using the WHO definition;
      renal function was classified by the estimated glomerular filtration rate (eGFR).
      RESULTS: In comparison with non-anaemic patients, anaemic patients had a
      significantly higher in-hospital mortality (4.9 vs 0.5%, P<0.001). Moreover, 1
      year mortality rates of anaemic patients were significantly higher regardless of
      whether they had a normal eGFR (22 vs 2.8%, P=0.029), an eGFR of 60-89 ml/min (14
      vs 4.2%, P<0.001), an eGFR of 30-59 ml/min (21 vs 3.7%, P<0.001) or an eGFR<30
      ml/min (26 vs 0%, NS). When cumulative mortality was analysed by haemoglobin
      concentrations in steps of 1 g/dl from <11.0 g/dl to >16.9 g/dl, 1-year mortality
      rates were 28, 18, 15, 5.5, 3.8, 5.7, 1.5 and 0%, respectively (P<0.001, log
      rank). Even after adjustment for comorbidities by multivariable Cox regression
      models, haemoglobin remained a significant predictor of long-term mortality
      (hazard rate ratio 0.77, 95% confidence interval (CI): 0.62-0.82, P<0.001) while
      eGFR was not (hazard rate ratio 1.0, 95% CI: 0.99-1.01). CONCLUSIONS: Anaemia was
      found to be a strong and independent predictor of acute and long-term mortality
      in patients with symptomatic CHD, regardless of the presence of CKD.

PMID- 17452412
TI  - A comparative study of methods of estimating kidney length in kidney
      transplantation donors.
AB  - BACKGROUND: Knowledge of kidney size is important for clinical assessment of
      renal disease. However, there are few studies on methods of assessing kidney
      size. The purpose of this study was to determine the usefulness of body index and
      radiological measurements for prediction of kidney size. METHODS: One hundred and
      twenty five donors were enrolled. The sizes of donor kidneys obtained after
      nephrectomies for kidney transplantations were documented and the correlation
      coefficient between kidney length and body index was calculated. Kidney length
      was estimated from the distance between the first and third lumbar vertebrae (L1
      3), intravenous pyelograms (IVPs), abdominal ultrasonography (US), and abdominal
      computed tomography (CT). RESULTS: Normal adult kidneys were 11.08 +/- 0.96 cm
      long, 6.25 +/- 0.67 cm wide, 4.73 +/- 0.65 cm thick and weighed 196.3 +/- 41.0 g.
      Correlation coefficients between kidney length and body height, body weight, body
      surface area and total body water content were 0.29, 0.31, 0.26, and 0.32,
      respectively. The difference between actual and predicted kidney lengths was -0.6
      cm for L1-3, +1.2 cm for IVPs, -0.7 cm for abdominal US, -0.8 cm for transverse
      CT section, and -0.5 cm for coronal CT section. CONCLUSIONS: Abdominal coronal CT
      section predicted kidney length more accurately than other radiological methods,
      but all radiological methods were associated with prediction errors. As kidney
      length was correlated with body index, it is suggested that body index is the
      most useful and simplest method of estimating kidney size as an adjunct to
      treatment decisions concerning renal disease.

PMID- 17452413
TI  - Influence of sirolimus on proteinuria in de novo kidney transplantation with
      expanded criteria donors: comparison of two CNI-free protocols.
AB  - BACKGROUND: The contribution of mammalian target of rapamycin (mTOR) inhibitors
      to proteinuria is controversial. The aim was to analyse proteinuria in suboptimal
      kidney calcineurin inhibitor-(CNI) free de novo immunosuppression. METHODS: All
      patients from our centre with donors >60 years and CNI-free treatment were
      included (n = 108). Patients were divided into two groups: (i) SRL group:
      sirolimus (SRL) + prednisone + mycophenolate mofetil (MMF) + antiCD25; (ii) MMF
      group: prednisone + MMF w/ or w/o antiCD25 (n = 75). Follow-up was 12 months.
      RESULTS: Donors were slightly younger in the SRL group (68 vs 71 years; P <
      0.05), receptor age (67 vs 65 years) was not significantly different. Patient
      survival in the MMF group was 88 vs 94% in the SRL group, however, these
      differences did not reach statistical significance. One-year graft survival
      censored for death was 83% in the MMF group and 94% in the SRL group. Acute
      rejection rate was 45% in the MMF and 15% in the SRL group (P < 0.01). The
      incidence of CNI introduction was higher in the MMF-group (35 vs 5; P < 0.05).
      The intention-to-treat analysis revealed significant differences of proteinuria
      [SRL vs MMF at 12 months: 461 (163-6988) vs 270 (53-3029) mg/day], which did not
      exist in the on-therapy (OT) analysis [SRL vs MMF at 12 months: 357 (199-1428) vs
      279 (53-3029) mg/day]. New onset nephrotic range proteinuria seemed to occur
      slightly more frequently in SRL patients (3/33 vs 1/75; P = 0.049), however, all
      four cases occurred in a context of recurrent disease, or previous drug
      independent damage or non-adherence. All of these patients were converted to CNI.
      CONCLUSION: SRL-based compared with MMF-based treatment in kidney transplantation
      with advanced age donors is associated with an acceptable outcome, however, with
      increased proteinuria in the intention-to-treat analysis. A large subgroup of the
      patients in the MMF group experienced acute rejection and required conversion to
      CNI.

PMID- 17452414
TI  - Mesangiolipidosis in Alagille syndrome--relationship with apolipoprotein A-I.

PMID- 17452415
TI  - Reduced coronary flow reserve in young adults with renal transplant.
AB  - BACKGROUND: Some degree of cardiovascular disease should be suspected in young
      adults who have been paediatric renal transplant recipients also if no systematic
      data collection is routinely performed in clinical setting. The aim of our work
      was to evaluate the degree of cardiovascular damage in these young patients,
      using a minimally invasive technique. We then evaluated coronary flow reserve
      (CFR) and carotid intima-media thickness (IMT) in 25 patients (13 males, median
      age 23.7 years). METHODS: Coronary flow velocity on the left anterior descending
      coronary artery was assessed by transthoracic echocardiography, before and after
      dipyridamole, after standard echocardiography. CFR was compared with that of a
      small control group (n = 16; median age 25 yrs). RESULTS: In this relatively
      young sample, mean CFR was 2.8 +/- 0.6 (median 2.75), and half of the patients
      had reduced coronary reserve (P = 0.01). Mean IMT (0.48 +/- 0.08 mm) was only
      slightly, though significantly larger compared with the reference standard (P <
      0.05) but was significantly thinner in normotensive than in hypertensive patients
      (0.42 +/- 0.06 vs 0.49 +/- 0.05 mm, P < 0.05). The time on dialysis prior to
      transplantation, hypertension and age at the time of CFR evaluation affect CFR.
      IMT did not correlate with CFR. CONCLUSIONS: CFR and IMT abnormalities are common
      in young transplant recipients, in spite of the fact that our paediatric
      population has much less of the atherosclerotic 'legacy' common to adult
      patients.

PMID- 17452416
TI  - Significance of endotoxaemia in chronic kidney disease.

PMID- 17452417
TI  - Impact of genetic knockout of PEPT2 on cefadroxil pharmacokinetics, renal tubular
      reabsorption, and brain penetration in mice.
AB  - The aim of this study was to examine the role of PEPT2, a proton-coupled
      oligopeptide transporter of the SLC15 family, on the disposition of the
      antibiotic cefadroxil in the body, particularly the kidney and brain.
      Pharmacokinetic, tissue distribution, and renal clearance studies were performed
      in wild-type and PEPT2 null mice after intravenous bolus administration of
      [(3)H]cefadroxil at 1, 12.5, 50, and 100 nmol/g body weight. Studies were also
      performed in the absence and presence of probenecid and quinine. Cefadroxil
      disposition kinetics was clearly nonlinear over the dose range studied (1-100
      nmol/g), which was attributed to both saturable renal tubular secretion and
      reabsorption of the antibiotic. After an intravenous bolus dose of 1 nmol/g
      cefadroxil, PEPT2 null mice exhibited a 3-fold greater total clearance and 3-fold
      lower systemic concentrations of drug compared with wild-type animals. Renal
      clearance studies further demonstrated that the renal reabsorption of cefadroxil
      was almost completely abolished in PEPT2 null versus wild-type mice (3% versus
      70%, p < 0.001). Of the 70% of cefadroxil reabsorbed in wild-type mice, PEPT2
      accounted for 95% and PEPT1 accounted for 5% of reabsorbed substrate. Tissue
      distribution studies indicated that PEPT2 had a dramatic effect on cefadroxil
      tissue exposure, especially in brain where the cerebrospinal fluid (CSF)-to-blood
      concentration ratio of cefadroxil was 6-fold greater in PEPT2 null mice compared
      with wild-type animals. These findings demonstrate that renal PEPT2 is almost
      entirely responsible for the reabsorption of cefadroxil in kidney and that
      choroid plexus PEPT2 limits the exposure of cefadroxil (and perhaps other
      aminocephalosporins) in CSF.

PMID- 17452419
TI  - Centrally administered nociceptin/orphanin FQ (N/OFQ) evokes bradycardia,
      hypotension, and diuresis in mice via activation of central N/OFQ peptide
      receptors.
AB  - The present studies examined the cardiovascular and renal responses produced by
      activation of central nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptors in
      conscious mice. To assess this, we examined changes in heart rate (HR), mean
      arterial pressure (MAP), urine output (V), urinary sodium excretion (UNaV), and
      free water clearance (CH(2)O) produced by acute i.c.v. injection of N/OFQ (0.03,
      0.3, 1, or 3 nmol) or isotonic saline vehicle (2 mul) in conscious telemetered
      ICR-CD1 mice. After i.c.v. injection, N/OFQ, but not vehicle, dose dependently
      decreased HR and MAP and increased V. At 3 nmol, N/OFQ reduced HR [control (C),
      672 +/- 23 beats/min; 20 min, 411 +/- 30 beats/min] and MAP (C, 108 +/- 4 mm Hg;
      20 min, 62 +/- 6 mm Hg). In the same telemetered mice, i.c.v. N/OFQ significantly
      elevated V (0.65 +/- 0.03 cc/2 h) compared with levels for the vehicle-treated
      group (0.15 +/- 0.09 cc/2 h). Central N/OFQ/vehicle did not alter UNaV or CH(2)O.
      In separate studies, 2-h i.c.v. pretreatment with the NOP receptor antagonist UFP
      101 ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2)) (10 or 30 nmol) markedly, but
      transiently, reduced HR but not MAP, V, UNaV, or CH(2)O. After 2-h UFP-101 (10 or
      30 nmol) pretreatment, subsequent i.c.v. injection of N/OFQ (1 or 3 nmol) failed
      to alter cardiovascular or renal function. In contrast, in separate mice, 2-h
      pretreatment with N/OFQ (1 or 3 nmol) or vehicle failed to prevent the
      cardiodepressor and diuretic responses to a subsequent i.c.v. injection of the
      same dose of N/OFQ. Together, these findings demonstrate that in conscious mice,
      the central administration of N/OFQ evokes marked bradycardia, hypotension, and
      diuresis by selective activation of central NOP receptors.

PMID- 17452418
TI  - Esterase inhibition by grapefruit juice flavonoids leading to a new drug
      interaction.
AB  - Our previous studies described a newly identified potential of grapefruit juice
      (GFJ) in mediating pharmacokinetic drug interactions due to its capability of
      esterase inhibition. The current study identifies the active components in GFJ
      responsible for its esterase-inhibitory effect. The esterase-inhibitory potential
      of 10 constitutive flavonoids and furanocoumarins toward p-nitrophenylacetate
      (PNPA) hydrolysis was investigated. The furanocoumarins bergamottin, 6',7'
      dihydroxybergamottin, and bergapten, and the glycoside flavonoids naringin and
      hesperidin, at concentrations found in GFJ or higher, did not inhibit the
      hydrolysis of PNPA by purified porcine esterase and human liver microsomes.
      However, the flavonoid aglycones morin, galangin, kaempferol, quercetin, and
      naringenin showed appreciable inhibition of PNPA hydrolysis in purified porcine
      esterase, and human and rat liver systems. In Caco-2 cells, demonstrated to
      contain minimal CYP3A activity, the permeability coefficient of the prodrugs
      lovastatin and enalapril was increased in the presence of the active flavonoids
      kaempferol and naringenin, consistent with inhibition of esterase activity. In
      rats, oral coadministration of kaempferol and naringenin with these prodrugs led
      to significant increases in plasma exposure to the active acids. In addition, in
      portal vein-cannulated rats, coadministration of lovastatin with kaempferol (10
      mg/kg) led to a 154% and a 113% increase in the portal plasma exposure to the
      prodrug and active acid, respectively, compared with coadministration with water.
      The contribution of CYP3A inhibition was demonstrated to be minimal. Overall, a
      series of flavonoids present in GFJ are identified as esterase inhibitors, of
      which kaempferol and naringenin are shown to mediate pharmacokinetic drug
      interaction with the prodrugs lovastatin and enalapril due to their capability of
      esterase inhibition.

PMID- 17452420
TI  - Combination silencer RNA (siRNA) targeting Bcl-2 antagonizes siRNA against
      thymidylate synthase in human tumor cell lines.
AB  - Nonspecific toxicity and resistance to traditional cytotoxic drugs are
      impediments to effective cancer therapy. Development of drugs targeting cellular
      molecules that mediate malignant characteristics may improve therapy. Antisense
      drugs that reduce mRNA and protein on which tumor cells depend for viability and
      treatment resistance are examples of such candidates. In particular, combining
      antisense drugs to simultaneously reduce multiple mRNAs/proteins is predicted to
      enhance antitumor effects. We hypothesized that combined treatment with silencer
      RNAs (siRNAs) targeting molecules mediating both proliferation (thymidylate
      synthase; TS) and survival (Bcl-2) would decrease proliferation and sensitize
      human tumor cells to nonantisense drugs in a greater-than-additive manner. We
      report that simultaneous treatment of human cervical carcinoma (HeLa) and breast
      tumor (MCF-7) cell lines with siRNAs targeting both TS and Bcl-2 had unexpected,
      nonreciprocal antagonistic effects. Two siRNAs targeting different Bcl-2 mRNA
      sequences reduced the capacity of TS siRNA to reduce TS mRNA and protein, with no
      evidence of converse effects by TS siRNA on Bcl-2 mRNA or protein. Moreover,
      treatment of HeLa cells with siRNA targeting Bcl-2 resulted in increased TS mRNA
      and protein. Pretreatment of HeLa and MCF-7 cells with TS siRNA sensitized cells
      to TS-targeting drugs, but addition of antagonistic Bcl-2 siRNA to the
      pretreatment regimen abrogated sensitization. Combined targeting of separate
      physiological pathways by antisense reagents may be a useful approach in
      treatment of cancer, but antagonistic interactions could abrogate advantages or
      reduce effectiveness of other antisense and nonantisense reagents.

PMID- 17452421
TI  - Using hapten design to discover therapeutic monoclonal antibodies for treating
      methamphetamine abuse.
AB  - When generating monoclonal antibodies (mAb) against small molecules, the chemical
      composition and molecular orientation of the drug-like hapten on the antigen is a
      crucial determinant. This is especially important when attempting to discover
      therapeutic mAb against the drugs of abuse (+)-methamphetamine [(+)-METH], (+)
      amphetamine [(+)-AMP], and the related compound (+)-3,4
      methylenedioxymethamphetamine [(+)-MDMA, the plus isomer in the racemic mixture
      known as MDMA or ecstasy]. The goal of these studies was to design and synthesize
      (+)-METH-like haptens with structural attributes that could make them effective
      for generating monoclonal antibodies for treating medical problems associated
      with these stimulant drugs of abuse. Five prototype (+)-METH-like haptens, which
      mimic structural aspects of these drugs, were synthesized and used to generate
      mAb. After screening for anti-(+)-METH IgG antibodies in more than 25,000
      potential mouse hybridoma cell lines, one prototype mAb from each of the five
      haptens was selected and studied in detail for molecular properties and
      preclinical efficacy. The amino acid sequences of the IgG-variable regions,
      structural models, affinity, and ligand specificity of each mAb were then used to
      help elucidate important therapeutic characteristics. Four of these antibodies
      exhibited high affinity and specificity to (+)-METH and (+)-MDMA; whereas one
      antibody (designated mAb4G9) exhibited high affinity and specificity to (+)-METH,
      (+)-MDMA, and (+)-AMP, without significant cross-reactivity against other METH
      like ligands, over-the-counter medications, or endogenous neurotransmitters.
      Considered together, discovery of mAb4G9 and the other antibodies in this report
      represent an important step in understanding the process for custom design of
      drug class-specific therapeutic antibodies for the treatment of drug addiction.

PMID- 17452422
TI  - A genome-wide microsatellite polymorphism database for the indica and japonica
      rice.
AB  - Microsatellite (MS) polymorphism is an important source of genetic diversity,
      providing support for map-based cloning and molecular breeding. We have developed
      a new database that contains 52 845 polymorphic MS loci between indica and
      japonica, composed of ample Class II MS markers, and integrated 18 828 MS loci
      from IRGSP and genetic markers from RGP. Based on genetic marker positions on the
      rice genome (http://rise.genomics.org.cn/rice2/index.jsp ), we determined the
      approximate genetic distances of these MS loci and validated 100 randomly
      selected markers experimentally with 90% success rate. In addition, we recorded
      polymorphic MS positions in indica cv. 9311 that is the most important paternal
      parent of the two-line hybrid rice in China. Our database will undoubtedly
      facilitate the application of MS markers in genetic researches and marker
      assisted breeding. The data set is freely available from
      www.wigs.zju.edu.cn/achievment/polySSR.

PMID- 17452423
TI  - Genome-wide analyses of the structural gene families involved in the legume
      specific 5-deoxyisoflavonoid biosynthesis of Lotus japonicus.
AB  - A model legume Lotus japonicus (Regel) K. Larsen is one of the subjects of genome
      sequencing and functional genomics programs. In the course of targeted approaches
      to the legume genomics, we analyzed the genes encoding enzymes involved in the
      biosynthesis of the legume-specific 5-deoxyisoflavonoid of L. japonicus, which
      produces isoflavan phytoalexins on elicitor treatment. The paralogous
      biosynthetic genes were assigned as comprehensively as possible by biochemical
      experiments, similarity searches, comparison of the gene structures, and
      phylogenetic analyses. Among the 10 biosynthetic genes investigated, six comprise
      multigene families, and in many cases they form gene clusters in the chromosomes.
      Semi-quantitative reverse transcriptase-PCR analyses showed coordinate up
      regulation of most of the genes during phytoalexin induction and complex
      accumulation patterns of the transcripts in different organs. Some paralogous
      genes exhibited similar expression specificities, suggesting their genetic
      redundancy. The molecular evolution of the biosynthetic genes is discussed. The
      results presented here provide reliable annotations of the genes and genetic
      markers for comparative and functional genomics of leguminous plants.

PMID- 17452424
TI  - Activation of the epidermal growth factor signalling pathway by tissue
      plasminogen activator in pancreas cancer cells.
AB  - BACKGROUND: Tissue plasminogen activator (tPA) is the major activator of
      plasminogen in plasma. This serine protease is overexpressed by exocrine pancreas
      tumour cells, where it promotes tumour cell proliferation, growth, and invasion.
      Here we have explored the signalling pathways used by tPA to activate the
      proliferation of pancreatic cancer cells. METHODS: Transcriptional profiling on
      cDNA micro arrays was used to analyse the pattern of gene expression in response
      to tPA compared to the response to epidermal growth factor (EGF) and platelet
      derived growth factor (PDGF). Results were confirmed using different biochemical
      assays in which specific kinase inhibitors or RNA interference were used.
      RESULTS: Transcriptional profiling showed that tPA modulates the expression of a
      set of genes commonly regulated by EGF, but distinct from the major set of genes
      modulated by PDGF. This suggested that tPA and EGF share common signalling
      pathways, a conclusion supported by further experimental evidence. Firstly, we
      found that tPA induced a rapid and transient phosphorylation of the EGFR.
      Secondly, specific EGFR kinase inhibitors, but not PDGFR kinase inhibitors,
      abolished the tPA induced phosphorylation of the ERK1/2 kinases and cell
      proliferation. The mitogenic activity of tPA was also inhibited by siRNA
      depletion of EGFR, thus confirming the involvement of this receptor in tPA
      triggered signalling. Thirdly, we show that the signalling and mitogenic effects
      of tPA require its proteolytic activity, the activity of the metalloprotease-9
      and active hb-EGF. CONCLUSION: Our results suggest that tPA induces proliferation
      by triggering a proteolytic cascade that sequentially activates plasmin,
      metalloprotease-9 (MMP-9) and hb-EGF. These events are required to activate the
      EGFR signalling pathway and cell proliferation.

PMID- 17452425
TI  - MELD score and serum sodium in the prediction of survival of patients with
      cirrhosis awaiting liver transplantation.
AB  - BACKGROUND/AIMS: Serum sodium predicts prognosis in cirrhosis and may improve the
      prognostic accuracy of the model for end-stage liver disease (MELD) score, but
      the available information is limited. The aim of the present study was to assess
      the prognostic value of serum sodium in the prediction of survival at 3 and 12
      months after listing in patients with cirrhosis awaiting liver transplantation,
      and to compare its predictive value with that of the MELD score. PATIENTS AND
      METHODS: 308 consecutive patients with cirrhosis listed for transplantation
      during a 5-year period were included in the study. The end-point was survival at
      3 and 12 months before transplantation. Variables obtained at the time of listing
      were analysed for prognostic value using multivariable analysis. Accuracy of
      prognostic variables was analysed by receiver operating characteristic (ROC)
      curves. RESULTS: The MELD score and serum sodium concentration were the only
      independent predictors of survival at 3 and 12 months after listing. Low serum
      sodium was associated with an increased risk of death in all subpopulations of
      patients with cirrhosis categorised according to the major complication developed
      before listing. The area under the ROC curves for serum sodium and MELD score was
      not significantly different both at 3 months (0.83 vs 0.79, respectively) and at
      12 months (0.70 vs 0.77, respectively). The addition of serum sodium did not
      significantly improve the accuracy of the MELD score in the prediction of
      survival at 3 and 12 months. CONCLUSION: In patients with cirrhosis awaiting
      liver transplantation, serum sodium and MELD were found to be independent
      predictors of survival. Larger studies are needed to determine whether the
      addition of serum sodium to MELD can improve its prognostic accuracy.

PMID- 17452426
TI  - Efficacy and safety of gemcitabine monotherapy in patients with transitional cell
      carcinoma after Cisplatin-containing therapy: a Japanese experience.
AB  - BACKGROUND: In Japan, the standard chemotherapy for advanced transitional cell
      carcinoma (TCC) of the urothelium is MVAC (methotrexate, vinblastine, adriamycin,
      cisplatin). However, a second-line therapy is still required for patients with
      recurrent TCC who discontinued MVAC because of toxicity or have MVAC refractory
      tumors. METHODS: We evaluated gemcitabine monotherapy in patients with advanced
      TCC who were previously treated with a platinum-based regimen. Gemcitabine (1000
      mg/m2) was given once a week for three consecutive weeks followed by a week of
      rest. This cycle was repeated at least three times, or until disease progression
      or intolerable adverse events were observed. RESULTS: Of the 46 patients entered
      into this study, 44 received gemcitabine. Performance status (PS) at study entry
      was: PS 0 (30 patients), PS 1 (12 patients) and PS 2 (2 patients). Stages III/IV
      were observed in 1/9 patients; the other 34 patients had relapsed after surgery.
      All 44 patients had been previously treated with a platinum-based regimen. The
      overall response rate was 25%, 1-year survival rate 52.3%, median survival time
      12.6 months and median progression free survival 3.1 months. The major grade 3/4
      hematological toxicity was neutropenia (47.7%), and the major grade 3/4 non
      hematological toxicity was anorexia (9.1%). All adverse drug reactions seen in
      the study were manageable. CONCLUSION: Gemcitabine monotherapy is a sufficiently
      active and well-tolerated therapy for patients who have previously undergone
      chemotherapy with a platinum-based regimen.

PMID- 17452427
TI  - Phase I study of cisplatin analogue nedaplatin, paclitaxel, and thoracic
      radiotherapy for unresectable stage III non-small cell lung cancer.
AB  - BACKGROUND: The standard treatment of unresectable stage III non-small cell lung
      cancer is concurrent chemoradiotherapy in patients in good general condition, but
      where the optimal chemotherapeutic regimen has not been determined. METHODS:
      Patients with unresectable stage III non-small cell lung cancer received
      nedaplatin (80 mg/m2) and paclitaxel on day 1 every 4 weeks for 3-4 cycles and
      concurrent thoracic radiotherapy (60 Gy/30 fractions for 6 weeks) starting on day
      1. The dose of paclitaxel was escalated from 120 mg/m2 in level 1, 135 mg/m2 in
      level 2 to 150 mg/m2 in level 3. RESULTS: A total of 18 patients (14 males and 4
      females, with a median age of 62.5 years) were evaluated in this study. Full
      cycles of chemotherapy were administered in 83% of patients in level 1, and in
      50% of patients in levels 2 and 3. No more than 50% of patients developed grade 4
      neutropenia. Transient grade 3 esophagitis and infection were noted in one
      patient, and unacceptable pneumonitis was noted in three (17%) patients, two of
      whom died of the toxicity. Dose-limiting toxicity (DLT), evaluated in 15
      patients, noted in one of the six patients in level 1, three of the six patients
      in level 2 and one of the three patients in level 3. One DLT at level 2 developed
      later as radiation pneumonitis. Thus, the maximum tolerated dose was determined
      to be level 1. The overall response rate (95% confidence interval) was 67% (41
      87%) with 12 partial responses. CONCLUSION: The doses of paclitaxel and
      nedaplatin could not be escalated as a result of severe pulmonary toxicity.

PMID- 17452429
TI  - The experience of massage during chemotherapy treatment in breast cancer
      patients.
AB  - This study aimed to describe the experience of massage for breast cancer patients
      during chemotherapy treatment. Ten patients received massage at five occasions.
      They were interviewed and analysis was conducted using Giorgi's ideas of
      phenomenological research. The essential meaning of getting massage during
      chemotherapy was described as a retreat from the feeling of uneasiness toward
      chemotherapy. Results revealed five themes: the patients experienced distraction
      from the frightening experience, a turn from negative to positive, a sense of
      relaxation, a confirmation of caring, and finally they just felt good. In
      conclusion, the findings of this study show that massage offered a retreat from
      uneasy, unwanted, negative feelings connected with chemotherapy treatment. It is
      a treatment that can be added to the arsenal of treatment choices available to
      the oncological staff.

PMID- 17452430
TI  - Investigating the removal of body piercings.
AB  - Although body piercing procurement continues to increase, 13% to 18% of them are
      removed. Reasons for piercing removal in college students were examined with
      three groups: (a) those who kept all their piercings, (b) those who removed some,
      or (c) those who removed all of their body piercings. Of the sample, 41% were
      still pierced; 50% in their lifetime. Their major purpose for the body piercing
      was "helped them feel unique." Females obtained more (in high school) and then
      removed more, usually as upperclassmen. Males and females reported themselves as
      risk takers at procedure time and currently; however, only 10% cited deviancy as
      a reason for the body piercing(s). Only removal elements of "I just got tired of
      it" and "I just decided to remove it" were present, especially with the Some
      Removed Group. Further examination of body piercing building personal
      distinctiveness and self-identity to promote their need of uniqueness is
      suggested.

PMID- 17452431
TI  - Predictors of patient satisfaction with telephone nursing services.
AB  - Patient satisfaction has been shown to be a factor in clinical outcomes, health
      care quality, and patient follow-through. Thus, a high level of satisfaction is a
      desired outcome of patient care. This article examines predictors of patient
      satisfaction with telephone nursing services among a sample of 1,939 respondents,
      using a conceptual model derived from the literature and preliminary work. The
      study was conducted in medical offices and call centers of a large national
      health maintenance organization. Calls were taped and content coded and then
      matched with caller questionnaire data. In the final multivariate predictive
      models, patient health status; caller ratings of expectations met by the nurse
      for listening, clarity, and collaboration; and nurse competence were the
      strongest predictors of satisfaction. Consistent with the literature, findings
      suggest that nurses should expand interpersonal communication skills, and systems
      should reduce barriers to effective listening, clarity, and collaboration with
      callers.

PMID- 17452432
TI  - Weight, exercise, and health: children's perceptions.
AB  - Childhood overweight is increasing, yet limited information is available on
      children's perspectives of overweight. The purpose of this investigation was to
      identify children's perspective of their weight, exercise, and health status.
      Participants were 17 children, 8 to 12 years of age, with body mass indexes > or
      = 95% for age and gender. A qualitative investigation using a phenomenological
      approach was conducted with a thematic analysis. Themes that emerged included
      intellectual disconnect, body image incongruence, social importance, and exercise
      perspectives. Children correctly identified healthy and unhealthy behaviors:
      dietary intake and physical activity. Children's knowledge about healthy dietary
      intake and physical activities disconnected from actual health practices.
      Children demonstrated confusion about physical activity requirements: frequency,
      intensity, and duration. Nurses need to develop strategies to bridge disconnect
      between what children know and actual dietary intake and physical activities.
      Nurses are fundamental to increasing children's knowledge of physical activity
      requirements for health promotion and disease prevention.

PMID- 17452433
TI  - Intrasubject medication adherence patterns.
AB  - The purpose of this prospective descriptive study was to explore the patterns of
      intrasubject (between medication) adherence of two similarly timed, twice-daily
      medications using the Medication Event Management System electronic monitoring
      cap. Medication adherence was measured for 6 months using electronic monitoring
      in 25 adult renal-transplant recipients. Data were available from 7,119
      electronic medication events. Results indicated that two twice-daily medications
      scheduled to be taken simultaneously were taken within 5 min of each other 77% of
      the time and within 10 min, 92% of the time. When only the first scheduled dose
      of the day was examined, the results are 79% and 95%, respectively. These
      findings are important to researchers and clinicians who must evaluate medication
      adherence in transplant recipients while balancing cost and subject burden. This
      study provides empirical support for monitoring a single immunosuppressive
      medication electronically to estimate medication adherence with double or triple
      immunosuppressive drug therapy.

PMID- 17452434
TI  - Alternative antibody Fab' fragment PEGylation strategies: combination of strong
      reducing agents, disruption of the interchain disulphide bond and disulphide
      engineering.
AB  - Antigen-binding fragments (Fab') of antibodies can be site specifically PEGylated
      at thiols using cysteine reactive PEG-maleimide conjugates. For therapeutic Fab'
      PEG, conjugation with 40 kDa of PEG at a single hinge cysteine has been found to
      confer appropriate pharmacokinetic properties to enable infrequent dosing.
      Previous methods have activated the hinge cysteine using mildly reducing
      conditions in order to retain an intact interchain disulphide. We demonstrate
      that the final Fab-PEG product does not need to retain the interchain disulphide
      and also therefore that strongly reducing conditions can be used. This
      alternative approach results in PEGylation efficiencies of 88 and 94% for human
      and murine Fab, respectively. It also enables accurate and efficient site
      specific multi-PEGylation. The use of the non-thiol reductant tris(2
      carboxyethyl) phosphine combined with protein engineering enables us to
      demonstrate the mono-, di- and tri-PEGylation of Fab fragments with a range of
      PEG size. We present evidence that PEGylated and unPEGylated Fab' molecules that
      lack an interchain disulphide bond retain very high levels of chemical and
      thermal stability and normal performance in PK and efficacy models.

PMID- 17452435
TI  - Phage display selection of Affibody molecules with specific binding to the
      extracellular domain of the epidermal growth factor receptor.
AB  - Affibody molecules specific for the epidermal growth factor receptor (EGFR) have
      been selected by phage display technology from a combinatorial protein library
      based on the 58-residue, protein A-derived Z domain. EGFR is overexpressed in
      various malignancies and is frequently associated with poor patient prognosis,
      and the information provided by targeting this receptor could facilitate both
      patient diagnostics and treatment. Three selected Affibody variants were shown to
      selectively bind to the extracellular domain of EGFR (EGFR-ECD). Kinetic
      biosensor analysis revealed that the three monomeric Affibody molecules bound
      with similar affinity, ranging from 130 to 185 nM. Head-to-tail dimers of the
      Affibody molecules were compared for their binding to recombinant EGFR-ECD in
      biosensor analysis and in human epithelial cancer A431 cells. Although the
      dimeric Affibody variants were found to bind in a range of 25-50 nM affinities in
      biosensor analysis, they were found to be low nanomolar binders in the cellular
      assays. Competition assays using radiolabeled Affibody dimers confirmed specific
      EGFR-binding and demonstrated that the three Affibody molecules competed for the
      same epitope. Immunofluorescence microscopy demonstrated that the selected
      Affibody dimers were initially binding to EGFR at the cell surface of A431, and
      confocal microscopy analysis showed that the Affibody dimers could thereafter be
      internalized. The potential use of the described Affibody molecules as targeting
      agents for radionuclide based imaging applications in various carcinomas is
      discussed.

PMID- 17452436
TI  - The intimidation of American physicians--banning partial-birth abortion.

PMID- 17452437
TI  - The partial death of abortion rights.

PMID- 17452438
TI  - Government in medicine.

PMID- 17452439
TI  - Audio interview: expanding federal funding for embryonic stem-cell research.
      Interview by Rachel Gotbaum.

PMID- 17452440
TI  - Mammalian DET1 regulates Cul4A activity and forms stable complexes with E2
      ubiquitin-conjugating enzymes.
AB  - DET1 (de-etiolated 1) is an essential negative regulator of plant light
      responses, and it is a component of the Arabidopsis thaliana CDD complex
      containing DDB1 and COP10 ubiquitin E2 variant. Human DET1 has recently been
      isolated as one of the DDB1- and Cul4A-associated factors, along with an array of
      WD40-containing substrate receptors of the Cul4A-DDB1 ubiquitin ligase. However,
      DET1 differs from conventional substrate receptors of cullin E3 ligases in both
      biochemical behavior and activity. Here we report that mammalian DET1 forms
      stable DDD-E2 complexes, consisting of DDB1, DDA1 (DET1, DDB1 associated 1), and
      a member of the UBE2E group of canonical ubiquitin-conjugating enzymes. DDD-E2
      complexes interact with multiple ubiquitin E3 ligases. We show that the E2
      component cannot maintain the ubiquitin thioester linkage once bound to the DDD
      core, rendering mammalian DDD-E2 equivalent to the Arabidopsis CDD complex. While
      free UBE2E-3 is active and able to enhance UbcH5/Cul4A activity, the DDD core
      specifically inhibits Cul4A-dependent polyubiquitin chain assembly in vitro.
      Overexpression of DET1 inhibits UV-induced CDT1 degradation in cultured cells.
      These findings demonstrate that the conserved DET1 complex modulates Cul4A
      functions by a novel mechanism.

PMID- 17452441
TI  - Translocation of mitochondrially synthesized Cox2 domains from the matrix to the
      intermembrane space.
AB  - The N-terminal and C-terminal domains of mitochondrially synthesized cytochrome c
      oxidase subunit II, Cox2, are translocated through the inner membrane to the
      intermembrane space (IMS). We investigated the distinct mechanisms of N-tail and
      C-tail export by analysis of epitope-tagged Cox2 variants encoded in
      Saccharomyces cerevisiae mitochondrial DNA. Both the N and C termini of a
      truncated protein lacking the Cox2 C-terminal domain were translocated to the IMS
      via a pathway dependent upon the conserved translocase Oxa1. The topology of this
      Cox2 variant, accumulated at steady state, was largely but not completely
      unaffected in mutants lacking proteins required for export of the C-tail domain,
      Cox18 and Mss2. C-tail export was blocked by truncation of the last 40 residues
      from the C-tail domain, indicating that sequence and/or structural features of
      this domain are required for its translocation. Mss2, a peripheral protein bound
      to the inner surface of the inner membrane, coimmunoprecipitated with full-length
      newly synthesized Cox2, whose leader peptide had already been cleaved in the IMS.
      Our data suggest that the C-tail domain is recognized posttranslationally by a
      specialized translocation apparatus after the N-tail has been translocated by
      Oxa1.

PMID- 17452442
TI  - Linear derivatives of Saccharomyces cerevisiae chromosome III can be maintained
      in the absence of autonomously replicating sequence elements.
AB  - Replication origins in Saccharomyces cerevisiae are spaced at intervals of
      approximately 40 kb. However, both measurements of replication fork rate and
      studies of hypomorphic alleles of genes encoding replication initiation proteins
      suggest the question of whether replication origins are more closely spaced than
      should be required. We approached this question by systematically deleting
      replicators from chromosome III. The first significant increase in loss rate
      detected for the 315-kb full-length chromosome occurred only after all five
      efficient chromosomal replicators in the left two-thirds of the chromosome
      (ARS305, ARS306, ARS307, ARS309, and ARS310) had been deleted. The removal of the
      inefficient replicator ARS308 from this originless region caused little or no
      additional increase in loss rate. Chromosome fragmentations that removed the
      normally inactive replicators on the left end of the chromosome or the
      replicators distal to ARS310 on the right arm showed that both groups of
      replicators contribute significantly to the maintenance of the originless
      chromosome. Surprisingly, a 142-kb derivative of chromosome III, lacking all
      sequences that function as autonomously replicating sequence elements in
      plasmids, replicated and segregated properly 97% of the time. Both the
      replication initiation protein ORC and telomeres or a linear topology were
      required for the maintenance of chromosome fragments lacking replicators.

PMID- 17452443
TI  - Adiponectin secretion is regulated by SIRT1 and the endoplasmic reticulum
      oxidoreductase Ero1-L alpha.
AB  - Adiponectin is secreted from adipose tissue in response to metabolic effectors in
      order to sensitize the liver and muscle to insulin. Reduced circulating levels of
      adiponectin that usually accompany obesity contribute to the associated insulin
      resistance. The molecular mechanisms controlling the production of adiponectin
      are essentially unknown. In this report, we demonstrate that the endoplasmic
      reticulum (ER) oxidoreductase Ero1-L alpha and effectors modulating peroxisome
      proliferator-activated receptor gamma (PPAR gamma) and SIRT1 activities regulate
      secretion of adiponectin from 3T3-L1 adipocytes. Specifically, adiponectin
      secretion and Ero1-L alpha expression are induced during the early phase of
      adipogenesis but are then down-regulated during the terminal phase, coincident
      with an increased expression of SIRT1. Suppression of SIRT1 or activation of PPAR
      gamma enhances Ero1-L alpha expression and stimulates secretion of high-molecular
      weight complexes of adiponectin in mature adipocytes. Suppression of Ero1-L alpha
      through expression of a corresponding small interfering RNA reduces adiponectin
      secretion during the differentiation of 3T3-L1 preadipocytes. Moreover, ectopic
      expression of Ero1-L alpha in Ero1-L alpha-deficient 3T3 fibroblasts stimulates
      the secretion of adiponectin following their conversion into adipocytes and
      prevents the suppression of adiponectin secretion in response to activation of
      SIRT1 by exposure to resveratrol. These findings provide a framework to
      understand the mechanisms by which adipocytes regulate secretion of adiponectin
      in response to various metabolic states.

PMID- 17452444
TI  - Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with muscle
      specific kinase.
AB  - Shc family proteins serve as phosphotyrosine adaptor molecules in various
      receptor-mediated signaling pathways. In mammals, three distinct Shc genes have
      been described that encode proteins characterized by two phosphotyrosine
      interaction modules, an amino-terminal phosphotyrosine binding (PTB) domain and a
      carboxy-terminal Src homology 2 domain. Here, we report the analysis of an
      uncharacterized fourth Shc family protein, ShcD/Shc4, that is expressed in adult
      brain and skeletal muscle. Consistent with this expression pattern, we find that
      ShcD can associate via its PTB domain with the phosphorylated muscle-specific
      kinase (MuSK) receptor tyrosine kinase and undergo tyrosine phosphorylation
      downstream of activated MuSK. Interestingly, additional sites of tyrosine
      phosphorylation, including a novel Grb2 binding site, are present on ShcD that
      are not found in other Shc family proteins. Activation of MuSK upon agrin binding
      at the neuromuscular junction (NMJ) induces clustering and tyrosine
      phosphorylation of acetylcholine receptors (AChRs) required for synaptic
      transmission. ShcD is coexpressed with MuSK in the postsynaptic region of the
      NMJ, and in cultured myotubes stimulated with agrin, expression of ShcD appears
      to be important for early tyrosine phosphorylation of the AChR. Thus, we have
      characterized a new member of the Shc family of docking proteins, which may
      mediate a specific aspect of signaling downstream of the MuSK receptor.

PMID- 17452445
TI  - Ubiquitination-induced conformational change within the deiodinase dimer is a
      switch regulating enzyme activity.
AB  - Ubiquitination is a critical posttranslational regulator of protein stability
      and/or subcellular localization. Here we show that ubiquitination can also
      regulate proteins by transiently inactivating enzymatic function through
      conformational change in a dimeric enzyme, which can be reversed upon
      deubiquitination. Our model system is the thyroid hormone-activating type 2
      deiodinase (D2), an endoplasmic reticulum-resident type 1 integral membrane
      enzyme. D2 exists as a homodimer maintained by interacting surfaces at its
      transmembrane and globular cytosolic domains. The D2 dimer associates with the
      Hedgehog-inducible ubiquitin ligase WSB-1, the ubiquitin conjugase UBC-7, and VDU
      1, a D2-specific deubiquitinase. Upon binding of T4, its natural substrate, D2 is
      ubiquitinated, which inactivates the enzyme by interfering with D2's globular
      interacting surfaces that are critical for dimerization and catalytic activity.
      This state of transient inactivity and change in dimer conformation persists
      until deubiquitination. The continuous association of D2 with this regulatory
      protein complex supports rapid cycles of deiodination, conjugation to ubiquitin,
      and enzyme reactivation by deubiquitination, allowing tight control of thyroid
      hormone action.

PMID- 17452446
TI  - Potential interface between ribosomal protein production and pre-rRNA processing.
AB  - It has become clear that in Saccharomyces cerevisiae the transcription of
      ribosomal protein genes, which makes up a major proportion of the total
      transcription by RNA polymerase II, is controlled by the interaction of three
      transcription factors, Rap1, Fhl1, and Ifh1. Of these, only Rap1 binds directly
      to DNA and only Ifh1 is absent when transcription is repressed. We have examined
      further the nature of this interaction and find that Ifh1 is actually associated
      with at least two complexes. In addition to its association with Rap1 and Fhl1,
      Ifh1 forms a complex (CURI) with casein kinase 2 (CK2), Utp22, and Rrp7. Fhl1 is
      loosely associated with the CURI complex; its absence partially destabilizes the
      complex. The CK2 within the complex phosphorylates Ifh1 in vitro but no other
      members of the complex. Two major components of this complex, Utp22 and Rrp7, are
      essential participants in the processing of pre-rRNA. Depletion of either
      protein, but not of other proteins in the early processing steps, brings about a
      substantial increase in ribosomal protein mRNA. We propose a model in which the
      CURI complex is a key mediator between the two parallel pathways necessary for
      ribosome synthesis: the transcription and processing of pre-rRNA and the
      transcription of ribosomal protein genes.

PMID- 17452447
TI  - Yra1 is required for S phase entry and affects Dia2 binding to replication
      origins.
AB  - The Saccharomyces cerevisiae F-box protein Dia2 is important for DNA replication
      and genomic stability. Using an affinity approach, we identified Yra1, a
      transcription-coupled mRNA export protein, as a Dia2 interaction partner. We find
      that yra1 mutants are sensitive to DIA2 expression levels. Like Dia2, Yra1
      associates with chromatin and binds replication origins, suggesting that they may
      function together in DNA replication. Consistent with this idea, Yra1 and Dia2
      coimmunoprecipitate with Hys2, a subunit of DNA polymerase delta. The C terminus
      of Yra1 is required to interact with Dia2. A yra1 mutant that lacks this domain
      is temperature sensitive yet has no apparent defect in RNA export. Remarkably,
      this mutant also fails to enter S phase at the nonpermissive temperature.
      Significantly, other mutants in transcription-coupled export do not exhibit S
      phase entry defects or sensitivity to DIA2 expression levels. Together, these
      results indicate that Yra1 has a role in DNA replication distinct from its role
      in mRNA export. Furthermore, Dia2 binding to replication origins is significantly
      reduced when association with Yra1 is compromised, suggesting that one aspect of
      the role of Yra1 in DNA replication may involve recruiting Dia2 to chromatin.

PMID- 17452448
TI  - CpG hypomethylation in a large domain encompassing the embryonic beta-like globin
      genes in primitive erythrocytes.
AB  - There is little evidence addressing the role of CpG methylation in
      transcriptional control of genes that do not contain CpG islands. This is
      reflected in the ongoing debate about whether CpG methylation merely suppresses
      retroelements or if it also plays a role in developmental and tissue-specific
      gene regulation. The genes of the beta-globin locus are an important model of
      mammalian developmental gene regulation and do not contain CpG islands. We have
      analyzed the methylation status of regions in the murine beta-like globin locus
      in uncultured primitive and definitive erythroblasts and other cultured primary
      and transformed cell types. A large ( approximately 20-kb) domain is
      hypomethylated only in primitive erythroid cells; it extends from the region just
      past the locus control region to before beta-major and encompasses the embryonic
      genes Ey, beta h1, and beta h0. Even retrotransposons in this region are
      hypomethylated in primitive erythroid cells. The existence of this large
      developmentally regulated domain of hypomethylation supports a mechanistic role
      for DNA methylation in developmental regulation of globin genes.

PMID- 17452449
TI  - A DOUBLETIME kinase binding domain on the Drosophila PERIOD protein is essential
      for its hyperphosphorylation, transcriptional repression, and circadian clock
      function.
AB  - A common feature of animal circadian clocks is the progressive phosphorylation of
      PERIOD (PER) proteins from hypo- to hyperphosphorylated species, events that are
      highly dependent on casein kinase 1 epsilon (termed DOUBLETIME [DBT] in
      Drosophila melanogaster) and necessary for normal clock progression. Drosophila
      PER (dPER) functions in the negative limb of the clockworks by presumably binding
      to the transcription factor CLOCK (CLK) and inhibiting its transactivation
      activity. Here, we identify a small region on dPER that is conserved with
      mammalian PERs and contains the major in vivo DBT binding domain, termed dPDBD
      (for dPER DBT binding domain). This domain is required for the manifestation of
      molecular and behavioral rhythms in vivo. In the absence of the dPDBD, the dPER
      protein is present at constant high levels throughout a daily cycle, undergoes
      little phosphorylation, and is severely impaired in its ability to function as a
      transcriptional repressor. Our findings indicate that the binding of dPER to CLK
      is not sufficient for transcriptional inhibition, implicating a more indirect
      mode of action whereby dPER acts as a molecular bridge to "deliver" DBT and/or
      other factors that directly repress CLK-dependent gene expression.

PMID- 17452450
TI  - Depletion of mammalian CCR4b deadenylase triggers elevation of the p27Kip1 mRNA
      level and impairs cell growth.
AB  - The stability of mRNA influences the abundance of cellular transcripts and
      proteins. Deadenylases play critical roles in mRNA turnover and thus are
      important for the regulation of various biological events. Here, we report the
      identification and characterization of CCR4b/CNOT6L, which is homologous to yeast
      CCR4 mRNA deadenylase. CCR4b is localized mainly in the cytoplasm and displays
      deadenylase activity both in vitro and in vivo. CCR4b forms a multisubunit
      complex similar to the yeast CCR4-NOT complex. Suppression of CCR4b by RNA
      interference results in growth retardation of NIH 3T3 cells accompanied by
      elevation of both p27(Kip1) mRNA and p27(Kip1) protein. Reintroduction of wild
      type CCR4b, but not mutant CCR4b lacking deadenylase activity, restores the
      growth of CCR4b-depleted NIH 3T3 cells. The data suggest that CCR4b regulates
      cell growth in a manner dependent on its deadenylase activity. We also show that
      p27(Kip1) mRNA is stabilized and its poly(A) tail is preserved in CCR4b-depleted
      cells. Our findings provide evidence that CCR4b deadenylase is a constituent of
      the mammalian CCR4-NOT complex and regulates the turnover rate of specific target
      mRNAs. Thus, CCR4b may be involved in various cellular events that include cell
      proliferation.

PMID- 17452451
TI  - Induction of Mxi1-SR alpha by FOXO3a contributes to repression of Myc-dependent
      gene expression.
AB  - Forkhead transcription factors of the O class (FOXOs) are important targets of
      the phosphatidylinositol 3-kinase (PI3-kinase)/Akt pathway. FOXOs have been
      implicated in the regulation of cell cycle progression, oxidative stress
      resistance, and apoptosis. Using DNA microarrays, we analyzed the transcriptional
      response to FOXO3a activation by gene expression analysis in DLD-1 colon cancer
      cells stably expressing a FOXO3a.A3-ER fusion protein. We found that activation
      of FOXO3a resulted in repression of a number of previously identified Myc target
      genes. Furthermore, FOXO3a activation induced expression of several members of
      the Mad/Mxd family of transcriptional repressors, most notably Mxi1. The
      induction of Mxi1 by FOXO3a was specific to the Mxi1-SR alpha isoform and was
      mediated by three highly conserved FOXO binding sites within the first intron of
      the gene. Activation of FOXO3a in response to inhibition of Akt also resulted in
      activation of Mxi1-SR alpha expression. Silencing of Mxi1 by small interfering
      RNA (siRNA) reduced FOXO3a-mediated repression of a number of Myc target genes.
      We also observed that FOXO3a activation induced a switch in promoter occupancy
      from Myc to Mxi1 on the E-box containing promoter regions of two Myc target
      genes, APEX and FOXM1. siRNA-mediated transient silencing of Mxi1 or all Mad/Mxd
      proteins reduced exit from S phase in response to FOXO3a activation, and stable
      silencing of Mxi1 or Mad1 reduced the growth inhibitory effect of FOXO3a. We
      conclude that induction of Mad/Mxd proteins contributes to the inhibition of
      proliferation in response to FOXO3a activation. Our results provide evidence of
      direct regulation of Mxi1 by FOXO3a and imply an additional mechanism through
      which the PI3-kinase/Akt/FOXO pathway can modulate Myc function.

PMID- 17452452
TI  - Epigenetic programming of the rRNA promoter by MBD3.
AB  - Within the human genome there are hundreds of copies of the rRNA gene, but only a
      fraction of these genes are active. Silencing through epigenetics has been
      extensively studied; however, it is essential to understand how active rRNA genes
      are maintained. Here, we propose a role for the methyl-CpG binding domain protein
      MBD3 in epigenetically maintaining active rRNA promoters. We show that MBD3 is
      localized to the nucleolus, colocalizes with upstream binding factor, and binds
      to unmethylated rRNA promoters. Knockdown of MBD3 by small interfering RNA
      results in increased methylation of the rRNA promoter coupled with a decrease in
      RNA polymerase I binding and pre-rRNA transcription. Conversely, overexpression
      of MBD3 results in decreased methylation of the rRNA promoter. Additionally,
      overexpression of MBD3 induces demethylation of nonreplicating plasmids
      containing the rRNA promoter. We demonstrate that this demethylation occurs
      following the overexpression of MBD3 and its increased interaction with the
      methylated rRNA promoter. This is the first demonstration that MBD3 is involved
      in inducing and maintaining the demethylated state of a specific promoter.

PMID- 17452453
TI  - A small conserved domain of Drosophila PERIOD is important for circadian
      phosphorylation, nuclear localization, and transcriptional repressor activity.
AB  - We identify in this study a 27-amino-acid motif which is conserved between the
      Drosophila melanogaster period protein (PER) and the three mammalian PERs.
      Characterization of PER lacking this motif (PER Delta) shows that it is important
      for phosphorylation of Drosophila PER by casein kinase I epsilon (CKI epsilon;
      doubletime protein or DBT) and CKII. S2 cell assays indicate that the domain also
      contributes significantly to PER nuclear localization as well as to PER
      transcriptional repressor activity. These two phenomena appear linked, since PER
      Delta transcriptional repressor activity in S2 cells was restored when nuclear
      localization was facilitated. Two less direct assays of PER Delta activity in
      flies can be interpreted similarly. The separate assay of nuclear import and
      export suggests that the domain functions in part to facilitate PER
      phosphorylation within the cytoplasm, which in turn promotes nuclear entry. As
      there is evidence that the kinases also function within the nucleus to promote
      transcriptional repression, we suggest that there is a subsequent collaboration
      between phosphorylated PER and the kinases to repress CLK-CYC activity, probably
      through the phosphorylation of CLK. This is then followed by additional PER
      phosphorylation, which occurs within the nucleus and leads to PER degradation.

PMID- 17452454
TI  - Unique requirement for Rb/E2F3 in neuronal migration: evidence for cell cycle
      independent functions.
AB  - The cell cycle regulatory retinoblastoma (Rb) protein is a key regulator of
      neural precursor proliferation; however, its role has been expanded to include a
      novel cell-autonomous role in mediating neuronal migration. We sought to
      determine the Rb-interacting factors that mediate both the cell cycle and
      migration defects. E2F1 and E2F3 are likely Rb-interacting candidates that we
      have shown to be deregulated in the absence of Rb. Using mice with compound null
      mutations of Rb and E2F1 or E2F3, we asked to what extent either E2F1 or E2F3
      interacts with Rb in neurogenesis. Here, we report that E2F1 and E2F3 are both
      functionally relevant targets in neural precursor proliferation, cell cycle exit,
      and laminar patterning. Each also partially mediates the Rb requirement for
      neuronal survival. Neuronal migration, however, is specifically mediated through
      E2F3, beyond its role in cell cycle regulation. This study not only outlines
      overlapping and distinct functions for E2Fs in neurogenesis but also is the first
      to establish a physiologically relevant role for the Rb/E2F pathway beyond cell
      cycle regulation in vivo.

PMID- 17452455
TI  - Yeast Rpb9 plays an important role in ubiquitylation and degradation of Rpb1 in
      response to UV-induced DNA damage.
AB  - Rpb9, a nonessential subunit of RNA polymerase II (Pol II), has multiple
      transcription-related functions in Saccharomyces cerevisiae, including
      transcription elongation and transcription-coupled repair (TCR). Here we show
      that, in response to UV radiation, Rpb9 also functions in promoting
      ubiquitylation and degradation of Rpb1, the largest subunit of Pol II. This
      function of Rpb9 is not affected by any pathways of nucleotide excision repair,
      including TCR mediated by Rpb9 itself and by Rad26. Rpb9 is composed of three
      distinct domains: the N-terminal Zn1, the C-terminal Zn2, and the central linker.
      The Zn2 domain, which is dispensable for transcription elongation and TCR
      functions, is essential for Rpb9 to promote Rpb1 degradation, whereas the Zn1 and
      linker domains, which are essential for transcription elongation and TCR
      functions, play a subsidiary role in Rpb1 degradation. Coimmunoprecipitation
      analysis suggests that almost the full length of Rpb9 is required for a strong
      interaction with the core Pol II: deletion of the Zn2 domain causes dramatically
      weakened interaction, whereas deletion of Zn1 and the linker resulted in
      undetectable interaction. Furthermore, we show that Rpb1, rather than the whole
      Pol II complex, is degraded in response to UV radiation and that the degradation
      is primarily mediated by the 26S proteasome.

PMID- 17452456
TI  - Contribution of polycomb homologues Bmi-1 and Mel-18 to medulloblastoma
      pathogenesis.
AB  - Bmi-1 and Mel-18 are structural homologues that belong to the Polycomb group of
      transcriptional regulators and are believed to stably maintain repression of gene
      expression by altering the state of chromatin at specific promoters. While a
      number of clinical and experimental observations have implicated Bmi-1 in human
      tumorigenesis, the role of Mel-18 in cancer cell growth has not been
      investigated. We report here that short hairpin RNA-mediated knockdown of either
      Bmi-1 or Mel-18 in human medulloblastoma DAOY cells results in the inhibition of
      proliferation, loss of clonogenic survival, anchorage-independent growth, and
      suppression of tumor formation in nude mice. Furthermore, overexpression of both
      Bmi-1 and Mel-18 significantly increases the clonogenic survival of Rat1
      fibroblasts. In contrast, stable downregulation of Bmi-1 or Mel-18 alone does not
      affect the growth of normal human WI38 fibroblasts. Proteomics-based
      characterization of Bmi-1 and Mel-18 protein complexes isolated from cancer cells
      revealed substantial similarities in their respective compositions. Finally, gene
      expression analysis identified a number of cancer-relevant pathways that may be
      controlled by Bmi-1 and Mel-18 and also showed that these Polycomb proteins
      regulate a set of common gene targets. Taken together, these results suggest that
      Bmi-1 and Mel-18 may have overlapping functions in cancer cell growth.

PMID- 17452457
TI  - Essential role of ubiquitin-specific protease 8 for receptor tyrosine kinase
      stability and endocytic trafficking in vivo.
AB  - Posttranslational modification by ubiquitin controls multiple cellular functions
      and is counteracted by the activities of deubiquitinating enzymes. UBPy (USP8) is
      a growth-regulated ubiquitin isopeptidase that interacts with the HRS-STAM
      complex. Using Cre-loxP-mediated gene targeting in mice, we show that lack of
      UBPy results in embryonic lethality, whereas its conditional inactivation in
      adults causes fatal liver failure. The defect is accompanied by a strong
      reduction or absence of several growth factor receptor tyrosine kinases (RTKs),
      like epidermal growth factor receptor, hepatocyte growth factor receptor (c-met),
      and ERBB3. UBPy-deficient cells exhibit aberrantly enlarged early endosomes
      colocalizing with enhanced ubiquitination and have reduced levels of HRS and
      STAM2. Congruently immortalized cells gradually stop proliferation upon induced
      deletion of UBPy. These results unveil a central and nonredundant role of UBPy in
      growth regulation, endosomal sorting, and the control of RTKs in vivo.

PMID- 17452458
TI  - Cyclin D2 translocates p27 out of the nucleus and promotes its degradation at the
      G0-G1 transition.
AB  - The nuclear export and cytoplasmic degradation of the cyclin-dependent kinase
      inhibitor p27 are required for effective progression of the cell cycle through
      the G(0)-G(1) transition. The mechanism responsible for this translocation of p27
      has remained unclear, however. We now show that cyclin D2 directly links growth
      signaling with the nuclear export of p27 at the G(0)-G(1) transition in some cell
      types. The up-regulation of cyclin D2 in response to mitogenic stimulation was
      found to occur earlier than that of other D-type cyclins and in parallel with
      down-regulation of p27 at the G(0)-G(1) transition. RNA interference-mediated
      depletion of cyclin D2 inhibited the nuclear export of p27 and delayed its
      degradation at the G(0)-G(1) transition. In contrast, overexpression of cyclin D2
      in G(0) phase shifted the localization of p27 from the nucleus to the cytoplasm
      and reduced the stability of p27. Overexpression of the cyclin D2(T280A) mutant,
      whose export from the nucleus is impaired, prevented the translocation and
      degradation of p27. These results indicate that cyclin D2 translocates p27 from
      the nucleus into the cytoplasm for its KPC-dependent degradation at the G(0)-G(1)
      transition.

PMID- 17452459
TI  - Transcriptional activity of androgen receptor is modulated by two RNA splicing
      factors, PSF and p54nrb.
AB  - Nuclear receptors regulate gene activation or repression through dynamic
      interactions with coregulators. The interactions between nuclear receptors and
      RNA splicing factors link gene transcription initiation with pre-mRNA splicing,
      providing a coordinated control of the products of gene transcription. Here we
      report that two RNA splicing factors, PTB-associated splicing factor (PSF) and
      p54nrb, synergistically form protein complexes with the androgen receptor (AR) in
      a ligand-independent manner and inhibit its transcriptional activity. PSF does
      not affect AR protein stability, as in the case of the progesterone receptor, but
      impedes the interaction of AR with the androgen response element. Both splicing
      factors interact directly with mSin3A and attract mSin3A to the AR complex in a
      synergistic manner. The suppression of AR transcriptional activity by PSF and
      p54nrb is reversed by the inhibition of histone deacetylase activity. These data
      demonstrated that PSF and p54nrb complex with AR and play a key role in
      modulating AR-mediated gene transcription.

PMID- 17452460
TI  - HOXA9 participates in the transcriptional activation of E-selectin in endothelial
      cells.
AB  - The homeobox gene HOXA9 has recently been shown to be an important regulator of
      endothelial cell (EC) differentiation and activation in addition to its role in
      embryonic development and hematopoiesis. In this report, we have determined that
      the EC-leukocyte adhesion molecule E-selectin is a key target for HOXA9. The
      depletion of HOXA9 protein in ECs resulted in a significant and specific decrease
      in tumor necrosis factor alpha (TNF-alpha)-induced E-selectin gene expression. In
      addition, HOXA9 specifically activated the E-selectin gene promoter in ECs.
      Progressive deletional analyses together with site-specific mutagenesis of the E
      selectin promoter indicated that the Abd-B-like HOX DNA-binding motif,
      CAATTTTATTAA, located in the proximal region spanning bp -210 to -221 upstream of
      the transcription start site was crucial for the promoter induction by HOXA9.
      Both HOXA9 in EC nuclear extract and recombinant HOXA9 protein bound to this
      sequence in vitro. Moreover, we showed that HOXA9 binds temporally, in a TNF
      alpha-dependent manner, to the region containing this Abd-B-like element in vivo.
      We have thus identified a novel and functionally critical cis-regulatory element
      for TNF-alpha-mediated transient expression of the E-selectin gene. Further, we
      provide evidence that HOXA9 acts as an obligate proinflammatory factor by
      mediating cytokine induction of E-selectin.

PMID- 17452461
TI  - Potentiation of astrogliogenesis by STAT3-mediated activation of bone
      morphogenetic protein-Smad signaling in neural stem cells.
AB  - Astrocytes play important roles in brain development and injury response.
      Transcription factors STAT3 and Smad1, activated by leukemia inhibitory factor
      (LIF) and bone morphogenetic protein 2 (BMP2), respectively, form a complex with
      the coactivator p300 to synergistically induce astrocytes from neuroepithelial
      cells (NECs) (K. Nakashima, M. Yanagisawa, H. Arakawa, N. Kimura, T. Hisatsune,
      M. Kawabata, K. Miyazono, and T. Taga, Science 284:479-482, 1999). However, the
      mechanisms that govern astrogliogenesis during the determination of the fate of
      neural stem cells remain elusive. Here we found that LIF induces expression of
      BMP2 via STAT3 activation and leads to the consequent activation of Smad1 to
      efficiently promote astrogliogenic differentiation of NECs. The BMP antagonist
      Noggin abrogated LIF-induced Smad1 activation and astrogliogenesis by inhibiting
      BMPs produced by NECs. NECs deficient in suppressor of cytokine signaling 3
      (SOCS3), a negative regulator of STAT3, readily differentiated into astrocytes
      upon activation by LIF not only due to sustained activation of STAT3 but also
      because of the consequent activation of Smad1. Our study suggests a novel LIF
      triggered positive regulatory loop that enhances astrogliogenesis.

PMID- 17452462
TI  - Noncanonical function of MEKK2 and MEK5 PB1 domains for coordinated extracellular
      signal-regulated kinase 5 and c-Jun N-terminal kinase signaling.
AB  - MEKK2 and MEK5 encode Phox/Bem1p (PB1) domains that heterodimerize with one
      another. MEKK2, MEK5, and extracellular signal-related kinase 5 (ERK5) form a
      ternary complex through interactions involving the MEKK2 and MEK5 PB1 domains and
      a 34-amino-acid C-terminal extension of the MEK5 PB1 domain. This C-terminal
      extension encodes an ERK5 docking site required for MEK5 activation of ERK5. The
      PB1 domains bind in a front-to-back arrangement, with a cluster of basic amino
      acids in the front of the MEKK2 PB1 domain binding to the back-end acidic
      clusters of the MEK5 PB1 domain. The C-terminal moiety, including the acidic
      cluster of the MEKK2 PB1 domain, is not required for MEK5 binding and binds MKK7.
      Quiescent MEKK2 preferentially binds MEK5, and MEKK2 activation results in ERK5
      activation. Activated MEKK2 binds and activates MKK7, leading to JNK activation.
      The findings define how the MEKK2 and MEK5 PB1 domains are uniquely used for
      differential binding of two mitogen-activated protein kinase kinases, MEK5 and
      MKK7, for the coordinated control of ERK5 and c-Jun N-terminal kinase activation.

PMID- 17452463
TI  - Regulation of P-TEFb elongation complex activity by CDK9 acetylation.
AB  - P-TEFb, comprised of CDK9 and a cyclin T subunit, is a global transcriptional
      elongation factor important for most RNA polymerase II (pol II) transcription. P
      TEFb facilitates transcription elongation in part by phosphorylating Ser2 of the
      heptapeptide repeat of the carboxy-terminal domain (CTD) of the largest subunit
      of pol II. Previous studies have shown that P-TEFb is subjected to negative
      regulation by forming an inactive complex with 7SK small RNA and HEXIM1. In an
      effort to investigate the molecular mechanism by which corepressor N-CoR mediates
      transcription repression, we identified HEXIM1 as an N-CoR-interacting protein.
      This finding led us to test whether the P-TEFb complex is regulated by
      acetylation. We demonstrate that CDK9 is an acetylated protein in cells and can
      be acetylated by p300 in vitro. Through both in vitro and in vivo assays, we
      identified lysine 44 of CDK9 as a major acetylation site. We present evidence
      that CDK9 is regulated by N-CoR and its associated HDAC3 and that acetylation of
      CDK9 affects its ability to phosphorylate the CTD of pol II. These results
      suggest that acetylation of CDK9 is an important posttranslational modification
      that is involved in regulating P-TEFb transcriptional elongation function.

PMID- 17452464
TI  - Functional role of CREB-binding protein in the circadian clock system of
      Drosophila melanogaster.
AB  - Rhythmic histone acetylation underlies the oscillating expression of clock genes
      in the mammalian circadian clock system. Cellular factors that contain histone
      acetyltransferase and histone deacetylase activity have been implicated in these
      processes by direct interactions with clock genes, but their functional relevance
      remains to be assessed by use of appropriate animal models. Here, using
      transgenic fly models, we show that CREB-binding protein (CBP) participates in
      the transcriptional regulation of the Drosophila CLOCK/CYCLE (dCLK/CYC)
      heterodimer. CBP knockdown in pigment dispersing factor-expressing cells
      lengthens the period of adult locomotor rhythm with the prolonged expression of
      period and timeless genes, while CBP overexpression in timeless-expressing cells
      causes arrhythmic circadian behaviors with the impaired expression of these
      dCLK/CYC-induced clock genes. In contrast to the mammalian circadian clock
      system, CBP overexpression attenuates the transcriptional activity of the
      dCLK/CYC heterodimer in cultured cells, possibly by targeting the PER-ARNT-SIM
      domain of dCLK. Our data suggest that the Drosophila circadian clock system has
      evolved a distinct mechanism to tightly regulate the robust transcriptional
      potency of the dCLK/CYC heterodimer.

PMID- 17452465
TI  - Evidence of endogenous mu opioid receptor regulation by epigenetic control of the
      promoters.
AB  - The pharmacological effect of morphine as a painkiller is mediated mainly via the
      mu opioid receptor (MOR) and is dependent on the number of MORs in the cell
      surface membrane. While several studies have reported that the MOR gene is
      regulated by various cis- and trans-acting factors, many questions remain
      unanswered regarding in vivo regulation. The present study shows that epigenetic
      silencing and activation of the MOR gene are achieved through coordinated
      regulation at both the histone and DNA levels. In P19 mouse embryonal carcinoma
      cells, expression of the MOR was greatly increased after neuronal
      differentiation. MOR expression could also be induced by a demethylating agent
      (5'-aza-2'-deoxycytidine) or histone deacetylase inhibitors in the P19 cells,
      suggesting involvement of DNA methylation and histone deacetylation for MOR gene
      silencing. Analysis of CpG DNA methylation revealed that the proximal promoter
      region was unmethylated in differentiated cells compared to its hypermethylation
      in undifferentiated cells. In contrast, the methylation of other regions was not
      changed in either cell type. Similar methylation patterns were observed in the
      mouse brain. In vitro methylation of the MOR promoters suppressed promoter
      activity in the reporter assay. Upon differentiation, the in vivo interaction of
      MeCP2 was reduced in the MOR promoter region, coincident with histone
      modifications that are relevant to active transcription. When MeCP2 was disrupted
      using MeCP2 small interfering RNA, the endogenous MOR gene was increased. These
      data suggest that DNA methylation is closely linked to the MeCP2-mediated
      chromatin structure of the MOR gene. Here, we propose that an epigenetic
      mechanism consisting of DNA methylation and chromatin modification underlies the
      cell stage-specific mechanism of MOR gene expression.

PMID- 17452466
TI  - Production of high-affinity human monoclonal antibody fab fragments to the 19
      kilodalton C-terminal merozoite surface protein 1 of Plasmodium falciparum.
AB  - A combinatorial immunoglobulin gene library was constructed from peripheral blood
      lymphocytes of eight patients infected with Plasmodium falciparum and was
      screened for the production of human monoclonal antibody Fab fragments to the C
      terminal 19-kDa fragment of P. falciparum merozoite surface protein 1 (MSP
      1(19)). Three Fab clones recognized recombinant MSP-1(19) under nonreducing
      conditions. Indirect immunofluorescence microscopy demonstrated that three Fab
      clones stained the surfaces of late trophozoites/schizonts and merozoites of the
      FCR3 and 3D7 strains, suggesting the Fabs' reactivities to a conserved epitope.
      Sequence analysis of the heavy-chain genes revealed that the closest germ line V
      segments were VH1-8 and VH7-81, with 91% to 98% homology. The closest germ line D
      segment was D3-10, and the closest germ line J segment was JH4 or JH5, with 90%
      to 97% homology. In the light-chain genes, the closest germ line V segment was
      A27 for the Jkappa2, Jkappa4, and Jkappa5 segments. The dissociation constants of
      these Fab fragments for recombinant MSP-1(19) ranged from 1.09 x 10(-9) to 2.66 x
      10(-9) M. The binding of the three Fab fragments to MSP-1(19) was competitively
      inhibited by the anti-MSP-1(19) mouse monoclonal antibody 12.8, which inhibits
      erythrocyte invasion by merozoites. However, the human Fab fragment with the
      highest affinity did not inhibit in vitro growth of P. falciparum. This is the
      first report of gene analysis and bacterial expression of human monoclonal
      antibodies to P. falciparum MSP-1(19). The combinatorial immunoglobulin gene
      library derived from malaria patients provides a potential tool for producing
      high-affinity human antibodies specific for P. falciparum.

PMID- 17452467
TI  - Dynamics in prophage content of invasive and noninvasive M1 and M28 Streptococcus
      pyogenes isolates in The Netherlands from 1959 to 1996.
AB  - Invasive group A streptococcal (GAS) disease re-emerged in The Netherlands in the
      late 1980s. To seek an explanation for this resurgence, the genetic compositions
      of 22 M1 and 19 M28 GAS strains isolated in The Netherlands between 1960s and the
      mid-1990s were analyzed by using a mixed-genome DNA microarray. During this four
      decade period, M1 and especially M28 strains acquired prophages on at least eight
      occasions. All prophages carried a superantigen (speA2, speC, speK) or a
      streptodornase (sdaD2, sdn), both associated with invasive GAS disease. Invasive
      and noninvasive GAS strains did not differ in prophage acquisition, suggesting
      that there was an overall increase in the pathogenicity of M1 and M28 strains
      over the last four decades rather than emergence of hypervirulent subclones. The
      increased overall pathogenic potential may have contributed to the reemergence of
      invasive GAS disease in The Netherlands.

PMID- 17452468
TI  - Identification of an orphan response regulator required for the virulence of
      Francisella spp. and transcription of pathogenicity island genes.
AB  - Francisella tularensis is a category A agent of biowarfare/biodefense. Little is
      known about the regulation of virulence gene expression in Francisella spp.
      Comparatively few regulatory factors exist in Francisella, including those
      belonging to two-component systems (TCS). However, orphan members of typical TCS
      can be identified. To determine if orphan TCS members affect Francisella gene
      expression, a gene encoding a product with high similarity to the Salmonella PmrA
      response regulator (FTT1557c/FNU0663.2) was deleted in Francisella novicida (a
      model organism for F. tularensis). The F. novicida pmrA mutant was defective in
      survival/growth within human and murine macrophage cell lines and was 100%
      defective in virulence in mice at a dose of up to 10(8) CFU. In addition, the
      mutant strain demonstrated increased susceptibility to antimicrobial peptide
      killing, but no differences were observed between the lipid A of the mutant and
      the parental strain, as has been observed with pmrA mutants of other microbes.
      The F. novicida pmrA mutant was 100% protective as a single-dose vaccine when
      challenge was with 10(6) CFU of F. novicida but did not protect against type A
      Schu S4 wild-type challenge. DNA microarray analysis identified 65 genes
      regulated by PmrA. The majority of these genes were located in the region
      surrounding pmrA or within the Francisella pathogenicity island (FPI). These FPI
      genes are also regulated by MglA, but MglA does not regulate pmrA, nor does PmrA
      regulate MglA. Thus, the orphan response regulator PmrA is an important factor in
      controlling virulence in F. novicida, and a pmrA mutant strain is an effective
      vaccine against homologous challenge.

PMID- 17452469
TI  - Human monoclonal antibody AVP-21D9 to protective antigen reduces dissemination of
      the Bacillus anthracis Ames strain from the lungs in a rabbit model.
AB  - Dutch-belted and New Zealand White rabbits were passively immunized with AVP
      21D9, a human monoclonal antibody to protective antigen (PA), at the time of
      Bacillus anthracis spore challenge using either nasal instillation or aerosol
      challenge techniques. AVP-21D9 (10 mg/kg) completely protected both rabbit
      strains against lethal infection with Bacillus anthracis Ames spores, regardless
      of the inoculation method. Further, all but one of the passively immunized
      animals (23/24) were completely resistant to rechallenge with spores by either
      respiratory challenge method at 5 weeks after primary challenge. Analysis of the
      sera at 5 weeks after primary challenge showed that residual human anti-PA levels
      decreased by 85 to 95%, but low titers of rabbit-specific anti-PA titers were
      also measured. Both sources of anti-PA could have contributed to protection from
      rechallenge. In a subsequent study, bacteriological and histopathology analyses
      revealed that B. anthracis disseminated to the bloodstream in some naive animals
      as early as 24 h postchallenge and increased in frequency with time. AVP-21D9
      significantly reduced the dissemination of the bacteria to the bloodstream and to
      various organs following infection. Examination of tissue sections from infected
      control animals, stained with hematoxylin-eosin and the Gram stain, showed edema
      and/or hemorrhage in the lungs and the presence of bacteria in mediastinal lymph
      nodes, with necrosis and inflammation. Tissue sections from infected rabbits
      dosed with AVP-21D9 appeared comparable to corresponding tissues from uninfected
      animals despite lethal challenge with B. anthracis Ames spores. Concomitant
      treatment with AVP-21D9 at the time of challenge conferred complete protection in
      the rabbit inhalation anthrax model. Early treatment increased the efficacy
      progressively and in a dose-dependent manner. Thus, AVP-21D9 could offer an
      adjunct or alternative clinical treatment regimen against inhalation anthrax.

PMID- 17452470
TI  - Toll-like receptor 2-dependent NF-kappaB activation is involved in nontypeable
      Haemophilus influenzae-induced monocyte chemotactic protein 1 up-regulation in
      the spiral ligament fibrocytes of the inner ear.
AB  - Inner ear dysfunction secondary to chronic otitis media (OM), including high
      frequency sensorineural hearing loss or vertigo, is not uncommon. Although
      chronic middle ear inflammation is believed to cause inner ear dysfunction by
      entry of OM pathogen components or cytokines from the middle ear into the inner
      ear, the underlying mechanisms are not well understood. Previously, we
      demonstrated that the spiral ligament fibrocyte (SLF) cell line up-regulates
      monocyte chemotactic protein 1 (MCP-1) expression after treatment with
      nontypeable Haemophilus influenzae (NTHI), one of the most common OM pathogens.
      We hypothesized that the SLF-derived MCP-1 plays a role in inner ear inflammation
      secondary to OM that is responsible for hearing loss and dizziness. The purpose
      of this study was to investigate the signaling pathway involved in NTHI-induced
      MCP-1 up-regulation in SLFs. Here we show for the first time that NTHI induces
      MCP-1 up-regulation in the SLFs via Toll-like receptor 2 (TLR2)-dependent
      activation of NF-kappaB. TLR2(-/-)- and MyD88(-/-)-derived SLFs revealed
      involvement of TLR2 and MyD88 in NTHI-induced MCP-1 up-regulation. Studies using
      chemical inhibitors and dominant-negative constructs demonstrated that it is
      mediated by the IkappaKbeta-dependent IkappaBalpha phosphorylation and NTHI
      induced NF-kappaB nuclear translocation. Furthermore, we demonstrated that the
      binding of NF-kappaB to the enhancer region of MCP-1 is involved in this up
      regulation. In addition, we have identified a potential NF-kappaB motif that is
      responsive and specific to certain NTHI molecules or ligands. Further studies are
      necessary to reveal specific ligands of NTHI that activate host receptors. These
      results may provide us with new therapeutic strategies for prevention of inner
      ear dysfunction secondary to chronic middle ear inflammation.

PMID- 17452471
TI  - Fungicidal monoclonal antibody C7 binds to Candida albicans Als3.
AB  - Monoclonal antibody (MAb) C7 reacted with a >200-kDa component from the Candida
      albicans cell wall identified by matrix-assisted laser desorption ionization-time
      of-flight mass spectrometry as Als3. It also bound the recombinant N terminus of
      Als3. Binding of MAb C7 to Als3 may explain the biological activities exerted by
      the MAb on C. albicans.

PMID- 17452472
TI  - Use of a genetically defined double mutant strain of Bordetella bronchiseptica
      lacking adenylate cyclase and type III secretion as a live vaccine.
AB  - While most vaccines consisting of killed bacteria induce high serum antibody
      titers, they do not always confer protection as effective as that induced by
      infection, particularly against mucosal pathogens. Bordetella bronchiseptica is a
      gram-negative respiratory pathogen that is endemic in many nonhuman mammalian
      populations and causes substantial disease in a variety of animals. At least 14
      different live attenuated vaccines against this pathogen are available for use in
      a variety of livestock and companion animals. However, there are few published
      data on the makeup or efficacy of these vaccines. Here we report the use of a
      genetically engineered double mutant of B. bronchiseptica, which lacks adenylate
      cyclase and type III secretion, as a vaccine candidate. This strain is safe at
      high doses, even for highly immunocompromised animals, and induces immune
      responses that are protective against highly divergent B. bronchiseptica strains,
      preventing colonization in the lower respiratory tract and decreasing the
      bacterial burden in the upper respiratory tract. This novel B. bronchiseptica
      vaccine candidate induces strong local immunity while eliminating damage caused
      by the two predominant cytotoxic mechanisms.

PMID- 17452473
TI  - Adapter protein SH2-Bbeta stimulates actin-based motility of Listeria
      monocytogenes in a vasodilator-stimulated phosphoprotein (VASP)-dependent
      fashion.
AB  - SH2-Bbeta (Src homology 2 Bbeta) is an adapter protein that is required for
      maximal growth hormone-dependent actin reorganization in membrane ruffling and
      cell motility. Here we show that SH2-Bbeta is also required for maximal actin
      based motility of Listeria monocytogenes. SH2-Bbeta localizes to Listeria-induced
      actin tails and increases the rate of bacterial propulsion in infected cells and
      in cell extracts. Furthermore, Listeria motility is decreased in mouse embryo
      fibroblasts from SH2-B(-/-) mice. Both recruitment of SH2-Bbeta to Listeria and
      SH2-Bbeta stimulation of actin-based propulsion require the vasodilator
      stimulated phosphoprotein (VASP), which binds ActA at the surfaces of Listeria
      cells and enhances bacterial actin-based motility. SH2-Bbeta enhances actin-based
      movement of ActA-coated beads in a biomimetic actin-based motility assay,
      provided that VASP is present. In vitro binding assays show that SH2-Bbeta binds
      ActA but not VASP; however, binding to ActA is greater in the presence of VASP.
      Because VASP also plays an essential regulatory role in actin-based processes in
      eukaryotic cells, the present results provide mechanistic insight into the
      functions of both SH2-Bbeta and VASP in motility and also increase our
      understanding of the fundamental mechanism by which Listeria spreads.

PMID- 17452474
TI  - Regulation of P-fimbrial phase variation frequencies in Escherichia coli CFT073.
AB  - Adherence of uropathogenic Escherichia coli to host tissue is required for
      infection and is mediated by fimbriae, such as pyelonephritis-associated pili
      (Pap). Expression of P fimbriae is regulated by phase variation, and to date,
      phase transition frequencies have been measured only for pap regulatory region
      constructs integrated into the E. coli K-12 chromosome. The aim of this work was
      to measure P phase transition frequencies in clinical isolates for the first
      time, including frequencies for the sequenced strain E. coli CFT073. P
      fimbriation and associated phase transition frequencies were measured for two E.
      coli clinical isolates and compared with levels for homologous pap constructs in
      E. coli K-12. Fimbriation and off-to-on transition frequencies were always higher
      in the clinical isolate. It was concluded that the regulatory inputs controlling
      papI expression are likely to be different in E. coli CFT073 and E. coli K-12 as
      (i) phase variation could be stimulated in E. coli K-12 by induction of papI and
      (ii) the level of expression of a papI::gfp(+) fusion was higher in E. coli
      CFT073 than in E. coli K-12. Furthermore, phase transition frequencies for the
      two E. coli CFT073 pap clusters were shown to be different depending on the
      culture conditions, indicating that there is a hierarchy of expression depending
      on signal inputs.

PMID- 17452475
TI  - Vacuolating cytotoxin in Helicobacter pylori water-soluble proteins upregulates
      chemokine expression in human eosinophils via Ca2+ influx, mitochondrial reactive
      oxygen intermediates, and NF-kappaB activation.
AB  - Helicobacter pylori-infected gastric mucosa is characterized by infiltration of
      inflammatory cells such as neutrophils and eosinophils. However, little
      information is available on the relationship between H. pylori virulence factors
      and chemokine expression in eosinophils. This study investigates the role of
      vacuolating cytotoxin (VacA) in chemokine expression from human eosinophils.
      Eosinophils were isolated from the peripheral blood of healthy volunteers using a
      magnetic cell separation system. VacA(+) H. pylori water-soluble proteins (WSP)
      induced higher expression of interleukin-8, growth-related oncogene alpha,
      monocyte chemotactic protein 1, and RANTES (regulated on activation, normal, T
      cell expressed and secreted) than Vac(-) WSP in human eosinophils, as assessed by
      quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay.
      Purified VacA not only increased chemokine expression but also activated p65/p50
      NF-kappaB heterodimers and phosphorylated IkappaB kinase (IKK) alpha/beta signals
      in human eosinophils. Inhibition of NF-kappaB and IKK significantly decreased the
      chemokine expression in VacA-stimulated eosinophils. Furthermore, VacA-induced NF
      kappaB activation and chemokine release from eosinophils were dependent on Ca(2+)
      influx and mitochondrial generation of reactive oxygen intermediates (ROI). These
      results suggest that NF-kappaB and IKK signals via Ca(2+) influx and
      mitochondrial ROI play a role in the up-regulation of chemokine expression in
      eosinophils stimulated with H. pylori VacA.

PMID- 17452476
TI  - Interactions between epithelial cells and leukocytes in immunity and tissue
      homeostasis.
AB  - Epithelial cells (ECs) cover the surfaces of the body such as skin, airways, or
      the intestinal tract and provide an important link between the outside
      environment and the body interior. Leukocytes play a critical role in immunity,
      as they are the predominant cell population involved in inflammation and the only
      cells providing adaptive immune response to pathogenic microorganisms. ECs and
      leukocytes form a complex network, which regulates processes such as host
      defense, immunity, inflammation, tissue repair, and cancer growth. One of the
      most critical functions of ECs is to keep up a barrier to the outside and to
      protect the sensitive immune system from continuous contact with external
      microorganisms. An appropriate response to wounding or danger involves not only
      killing of microbes but also regulation of tissue repair and reconstitution of
      the barrier system. Dysregulated response to damage represents a
      pathophysiological mechanism, which leads to autoimmunity, chronic inflammatory
      diseases, and cancer development. The networks described here are involved in
      virtually all diseases that take place at body surfaces. In this article, we
      develop a concept of epithelial barrier as a critical regulator of leukocyte
      function and discuss how host defense processes modulate epithelial homeostasis.

PMID- 17452477
TI  - AM3 modulates dendritic cell pathogen recognition capabilities by targeting DC
      SIGN.
AB  - AM3 (Inmunoferon) is an orally effective immunomodulator that influences the
      regulatory and effector functions of the immune system whose molecular mechanisms
      of action are mostly unknown. We hypothesized that the polysaccharide moiety of
      AM3 (IF-S) might affect immune responses by modulating the lectin-dependent
      pathogen recognition abilities of human dendritic cells. IF-S inhibited binding
      of viral, fungal, and parasite pathogens by human monocyte-derived dendritic
      cells in a dose-dependent manner. IF-S specifically impaired the pathogen
      recognition capabilities of DC-SIGN, as it reduced the attachment of Candida,
      Aspergillus, and Leishmania to DC-SIGN transfectants. IF-S also inhibited the
      interaction of DC-SIGN with both its cellular counterreceptor (intercellular
      adhesion molecule 3) and the human immunodeficiency virus (HIV) type 1 gp120
      protein and blocked the DC-SIGN-dependent capture of HIV virions and the HIV
      trans-infection capability of DC-SIGN transfectants. IF-S promoted DC-SIGN
      internalization in DCs without affecting mannose receptor expression, and (1)D
      saturation transfer difference nuclear magnetic resonance demonstrated that IF-S
      directly interacts with DC-SIGN on the cell surface. Therefore, the
      polysaccharide moiety of AM3 directly influences pathogen recognition by
      dendritic cells by interacting with DC-SIGN. Our results indicate that DC-SIGN is
      the target for an immunomodulator and imply that the adjuvant and
      immunomodulatory actions of AM3 are mediated, at least in part, by alteration of
      the DC-SIGN functional activities.

PMID- 17452478
TI  - Modular structure of microcin H47 and colicin V.
AB  - Microcins are gene-encoded peptide antibiotics produced by enterobacteria that
      act on strains of gram-negative bacteria. In this work, we concentrated on higher
      molecular-mass microcins, i.e., those possessing 60 or more amino acids. They can
      be subdivided into unmodified and posttranslationally modified peptides. In both
      cases, they exhibit conserved C-terminal sequences that appear to be
      characteristic of each subgroup. In the hypothesis that these sequences could
      correspond to domains, gene fusions between the activity genes for the unmodified
      microcin colicin V and the modified microcin H47 were constructed. These two
      microcins differ in their mode of synthesis, uptake, target, and specific
      immunity. Through this experimental approach, chimeric peptides with exchanged C
      terminal sequences were encoded. Cells carrying the fusions in different genetic
      contexts were then assayed for antibiotic production. Many of them produced
      antibiotic activities with recombinant properties: the toxicity of one microcin
      and the mode of uptake of the other. The results led to the identification of a
      modular structure of colicin V and microcin H47, with the recognition of two
      domains in their peptide chains: a toxic N-terminal domain and an uptake C
      terminal domain. This modular design would be shared by other microcins from each
      subgroup.

PMID- 17452479
TI  - Enterobacteriaceae bloodstream infections: presence of integrons, risk factors,
      and outcome.
AB  - A prospective observational study was conducted to identify factors associated
      with bloodstream infections (BSIs) caused by integron-carrying Enterobacteriaceae
      and to evaluate the clinical significance of integron carriage. Consecutive
      patients with Enterobacteriaceae BSIs were identified and followed up until
      discharge or death. Identification of blood isolates and susceptibility testing
      were performed by the Wider I automated system. int-1-specific PCR, conserved
      segment PCR, and DNA sequencing were used to determine the presence, length, and
      content of integrons. The relatedness among the isolates was examined by pulsed
      field gel electrophoresis. Two hundred fifty episodes of Enterobacteriaceae BSI
      occurred in 233 patients; 109 (43.6%) were nosocomial, 82 (32.8%) were community
      acquired, and 59 (23.6%) were health care associated. Integrons were detected in
      11 (13.4%) community-acquired, 24 (40.7%) health care-associated, and 46 (42.2%)
      nosocomial isolates. Integron-carrying organisms were more likely to exhibit
      resistance to three or more classes of antimicrobials (odds ratio [OR], 9.84; 95%
      confidence interval [95% CI], 5.31 to 18.23; P < 0.001) or to produce extended
      spectrum beta-lactamases (OR, 5.75; 95% CI, 2.38 to 13.89; P < 0.001) or a VIM
      type metallo-beta-lactamase (P, 0.003). Inter- or intraspecies integron transfer
      and cross-transmission of integron-carrying clones were observed. Use of
      cotrimoxazole (OR, 4.77; 95% CI, 1.81 to 12.54; P < 0.001) and a nosocomial or
      other health care setting (OR, 3.07; 95% CI, 1.30 to 7.22; P, 0.01) were
      independently associated with BSIs caused by integron-carrying
      Enterobacteriaceae. Patients with a nonurinary source of bacteremia (OR, 9.46;
      95% CI, 2.77 to 32.32; P < 0.001) and a Pitt bacteremia score of > or =4 (OR,
      23.36; 95% CI, 7.97 to 68.44; P < 0.001) had a significantly higher 14-day
      mortality rate, whereas integron carriage did not affect clinical outcomes. These
      findings may have implications affecting antibiotic policies and infection
      control measures.

PMID- 17452480
TI  - Role of the ABC transporter PRP1 (ABCC7) in pentamidine resistance in Leishmania
      amastigotes.
AB  - Pentamidine is a second-line agent in the treatment of leishmaniasis whose mode
      of action and resistance mechanism are not well understood. In this work, we show
      that the intracellular ABC protein PRP1 (pentamidine resistance protein 1)
      (ABCC7) can confer resistance to pentamidine in Leishmania sp. parasites in the
      intracellular stage.

PMID- 17452481
TI  - In vitro susceptibilities of 217 clinical isolates of zygomycetes to conventional
      and new antifungal agents.
AB  - We evaluated the in vitro susceptibilities of 217 zygomycetes to amphotericin B,
      ketoconazole, fluconazole, itraconazole, voriconazole, posaconazole, caspofungin,
      and flucytosine. The significant in vitro activity of posaconazole against
      several species appears to support its reported clinical efficacy. Decreased
      susceptibility to amphotericin B was noted with Cunninghamella bertholletiae.

PMID- 17452482
TI  - Vibrio splendidus as the source of plasmid-mediated QnrS-like quinolone
      resistance determinants.

PMID- 17452483
TI  - Sultam thiourea inhibition of West Nile virus.
AB  - We have identified sultam thioureas as novel inhibitors of West Nile virus (WNV)
      replication. One such compound inhibited WNV, with a 50% effective concentration
      of 0.7 microM, and reduced reporter expression from cells that harbored a WNV
      based replicon. Our results demonstrate that sultam thioureas can block a
      postentry, preassembly step of WNV replication.

PMID- 17452484
TI  - A novel fluorescence intensity screening assay identifies new low-molecular
      weight inhibitors of the gp41 coiled-coil domain of human immunodeficiency virus
      type 1.
AB  - A metallopeptide-based fluorescence assay has been designed for the detection of
      small-molecule inhibitors of human immunodeficiency virus type 1 gp41, the viral
      protein involved in membrane fusion. The assay involves two peptides representing
      the inner N-terminal-heptad-repeat (HR1) coiled coil and the outer C-terminal
      heptad-repeat (HR2) helical domains of the gp41 six-helix bundle which forms
      prior to fusion. The two peptides span a hydrophobic pocket previously defined in
      the literature. The HR1 peptide is modified with a metal-ligated dye complex,
      which maintains structural integrity and permits association with a fluorophore
      labeled HR2 peptide to be followed by fluorescence quenching. Compounds able to
      disrupt six-helix bundle formation can act as fusion inhibitors, and we show that
      they can be detected in the assay from an increase in the fluorescence that is
      correlated with the potency of the compound. Assay optimization and validation
      have resulted in a simple quantitative competitive inhibition assay for fusion
      inhibitors that bind in the hydrophobic pocket. The assay has an assay quality
      factor (Z') of 0.88 and can rank order inhibitors at 10 microM concentration with
      K(i)s in the range of 0.2 microM to 30 microM, an ideal range for drug discovery.
      Screening of a small peptidomimetic library has yielded three new low-molecular
      weight gp41 inhibitors. In vitro syncytium inhibition assays confirmed that the
      compounds inhibited cell-cell fusion in the low micromolar range. These lead
      compounds provide a new molecular scaffold for the development of fusion
      inhibitors.

PMID- 17452485
TI  - Defining limits of treatment with humanized neutralizing monoclonal antibody for
      West Nile virus neurological infection in a hamster model.
AB  - A potent anti-West Nile virus (anti-WNV)-neutralizing humanized monoclonal
      antibody, hE16, was previously shown to improve the survival of WNV-infected
      hamsters when it was administered intraperitoneally (i.p.), even after the virus
      had infected neurons in the brain. In this study, we evaluated the therapeutic
      limit of hE16 for the treatment of WNV infection in hamsters by comparing single
      dose peripheral (i.p.) therapy with direct administration into the pons through a
      convection-enhanced delivery (CED) system. At day 5 after infection, treatments
      with hE16 by the peripheral and the CED routes were equally effective at reducing
      morbidity and mortality. In contrast, at day 6 only the treatment by the CED
      route protected the hamsters from lethal infection. These experiments suggest
      that hE16 can directly control WNV infection in the central nervous system. In
      support of this, hE16 administered i.p. was detected in a time-dependent manner
      in the serum, cerebrospinal fluid (CSF), cerebral cortex, brain stem, and spinal
      cord in CSF. A linear relationship between the hE16 dose and the concentration in
      serum was observed, and maximal therapeutic activity occurred at doses of 0.32
      mg/kg of body weight or higher, which produced serum hE16 concentrations of 1.3
      microg/ml or higher. Overall, these data suggest that in hamsters hE16 can
      ameliorate neurological disease after significant viral replication has occurred,
      although there is a time window that limits therapeutic efficacy.

PMID- 17452486
TI  - Pharmacokinetics and tolerability of a higher rifampin dose versus the standard
      dose in pulmonary tuberculosis patients.
AB  - Rifampin is a key drug for tuberculosis (TB) treatment. The available data
      suggest that the currently applied 10-mg/kg of body weight dose of rifampin may
      be too low and that increasing the dose may shorten the treatment duration. A
      double-blind randomized phase II clinical trial was performed to investigate the
      effect of a higher dose of rifampin in terms of pharmacokinetics and
      tolerability. Fifty newly diagnosed adult Indonesian TB patients were randomized
      to receive a standard (450-mg, i.e., 10-mg/kg in Indonesian patients) or higher
      (600-mg) dose of rifampin in addition to other TB drugs. A full pharmacokinetic
      curve for rifampin, pyrazinamide, and ethambutol was recorded after 6 weeks of
      daily TB treatment. Tolerability was assessed during the 6-month treatment
      period. The geometric means of exposure to rifampin (area under the concentration
      time curve from 0 to 24 h [AUC(0-24)]) were increased by 65% (P < 0.001) in the
      higher-dose group (79.7 mg.h/liter) compared to the standard-dose group (48.5
      mg.h/liter). Maximum rifampin concentrations (C(max)) were 15.6 mg/liter versus
      10.5 mg/liter (49% increase; P < 0.001). The percentage of patients for whom the
      rifampin C(max) was > or =8 mg/liter was 96% versus 79% (P = 0.094). The
      pharmacokinetics of pyrazinamide and ethambutol were similar in both groups. Mild
      (grade 1 or 2) hepatotoxicity was more common in the higher-dose group (46 versus
      20%; P = 0.054), but no patient developed severe hepatotoxicity. Increasing the
      rifampin dose was associated with a more than dose-proportional increase in the
      mean AUC(0-24) and C(max) of rifampin without affecting the incidence of serious
      adverse effects. Follow-up studies are warranted to assess whether high-dose
      rifampin may enable shortening of TB treatment.

PMID- 17452487
TI  - Combined therapies in a murine model of blastoschizomycosis.
AB  - In a murine model of blastoschizomycosis, amphotericin B combined with
      micafungin, flucytosine or voriconazole did not improve the efficacy of
      fluconazole. However, such combinations can constitute therapeutic options for
      those cases where fluconazole fails.

PMID- 17452488
TI  - Vancomycin in vitro bactericidal activity and its relationship to efficacy in
      clearance of methicillin-resistant Staphylococcus aureus bacteremia.
AB  - We examined the relationship between the time to clearance of methicillin
      resistant Staphylococcus aureus (MRSA) bacteremia while patients were receiving
      vancomycin therapy and the in vitro bactericidal activity of vancomycin.
      Vancomycin killing assays were performed with 34 MRSA bloodstream isolates (17
      accessory gene regulator group II [agr-II] and 17 non-agr-II isolates) from 34
      different patients with MRSA bacteremia for whom clinical and microbiological
      outcomes data were available. Vancomycin doses were prospectively adjusted to
      achieve peak plasma concentrations of 28 to 32 mug/ml and trough concentrations
      of 8 to 12 microg/ml. Bactericidal assays were performed over 24 h with
      approximately 10(7) to 10(8) CFU/ml in broth containing 16 microg/ml vancomycin.
      The median time to clearance of bacteremia was 6.5 days for patients with MRSA
      isolates demonstrating > or =2.5 reductions in log(10) CFU/ml at 24 h and >10.5
      days for patients with MRSA isolates demonstrating <2.5 log(10) CFU/ml by 24 h (P
      = 0.025). The median time to clearance was significantly longer with MRSA
      isolates with vancomycin MICs of 2.0 microg/ml compared to that with MRSA
      isolates with MICs of < or =1.0 microg/ml (P = 0.019). The bacteremia caused by
      MRSA isolates with absent or severely reduced delta-hemolysin expression was of a
      longer duration of bacteremia (10 days and 6.5 days, respectively; P = 0.27) and
      had a decreased probability of eradication (44% and 78%, respectively; P =
      0.086). We conclude that strain-specific microbiological features of MRSA, such
      as increased vancomycin MICs and decreased killing by vancomycin, appear to be
      predictive of prolonged MRSA bacteremia while patients are receiving vancomycin
      therapy. Prolonged bacteremia and decreased delta-hemolysin expression may also
      be related. Evaluation of these properties may be useful in the consideration of
      antimicrobial therapies that can be used as alternatives to vancomycin for the
      treatment of MRSA bacteremia.

PMID- 17452489
TI  - Multiple-dose escalation study of the safety, pharmacokinetics, and biologic
      activity of oral AMD070, a selective CXCR4 receptor inhibitor, in human subjects.
AB  - AMD070 is an oral CXCR4 antagonist with in vitro activity against X4-tropic human
      immunodeficiency virus type 1. Thirty fasting healthy male volunteers received
      oral doses of AMD070 ranging from a single 50-mg dose to seven 400-mg doses given
      every 12 h (q12h). Nine subjects received a 200-mg dose during fasting and prior
      to a meal. Subjects were monitored for safety and pharmacokinetics. AMD070 was
      well tolerated, without serious adverse events. Transient headaches (13 subjects)
      and neurocognitive (8 subjects) and gastrointestinal (7 subjects) symptoms were
      the most common complaints. Seven subjects had sinus tachycardia, and two were
      symptomatic. AMD070 plasma concentrations peaked 1 to 2 h after patient dosing.
      The estimated terminal half-life ranged from 11.2 to 15.9 h among cohorts. Dose
      proportionality was not demonstrated. Less than 1% of the drug appeared unchanged
      in the urine. Food reduced the maximum concentration of drug in serum and the
      area under the concentration-time curve from 0 to 24 h by 70% and 56%,
      respectively (P < or = 0.01). A dose-dependent elevation of white blood cells
      (WBC) demonstrated a maximum twofold increase over baseline (95% confidence
      interval, 2.0- to 2.1-fold) in an E(max) model. In healthy volunteers, AMD070 was
      well tolerated and demonstrated mixed-order pharmacokinetics, and food reduced
      drug exposure. AMD070 induced a dose-related elevation of WBC which was
      attributed to CXCR4 blockade. Using leukocytosis as a surrogate marker for CXCR4
      inhibition, this dose-response relationship suggests that the doses used in this
      study were active in vivo, though not maximal, throughout the dosing interval.
      Trough concentrations with the 400-mg dose q12h exceeded the antiviral in vitro
      90% effective concentration of AMD070.

PMID- 17452491
TI  - Upper-limb botulinum toxin A injection and occupational therapy in children with
      hemiplegic cerebral palsy identified from a population register: a single-blind,
      randomized, controlled trial.
AB  - OBJECTIVES: The purpose of this work was to assess the effect of botulinum toxin
      A and occupational therapy compared with occupational therapy alone on body
      structure, activities participation, and self-perception in a sample of children
      (aged 3-16 years) with hemiplegic cerebral palsy recruited from a statewide
      register. PATIENTS AND METHODS: Participants of this single-blind, randomized,
      controlled trial identified from a population-based cerebral palsy register
      received either an individually prescribed and localized injection of botulinum
      toxin A with 4 sessions of occupational therapy over 4 weeks (intervention) or
      occupational therapy alone (control). Outcomes were assessed from 2 domains of
      the World Health Organization International Classification of Functioning,
      Disability, and Health: body structure (Modified Ashworth Scale and Tardieu
      Scale) and activities participation (Assessment of Motor and Process Skills, Goal
      Attainment Scale, Pediatric Evaluation of Disability Inventory, and Pediatric
      Quality of Life Inventory). Self-perception was also measured. RESULTS: All of
      the participants (intervention: n = 21; control: n = 22) provided data at
      baseline and 3 and 6 months. Mean age was 8.6 years; 23 were boys and 20 were
      girls. At 3 months, children allocated to receive the intervention performed
      significantly better in terms of body structure and activities participation.
      They reported improvements in self-perception for the global self-worth domain.
      At 6 months, the differences between the intervention and control groups
      persisted for the measures of body structure but not for activities participation
      or self-perception. CONCLUSION: Botulinum toxin A injection combined with a low
      intensity occupational therapy program achieves significant improvements in body
      structure, activity participation, and self-perception.

PMID- 17452490
TI  - Heparin-mimicking sulfonic acid polymers as multitarget inhibitors of human
      immunodeficiency virus type 1 Tat and gp120 proteins.
AB  - Human immunodeficiency virus (HIV) Tat and gp120 intriguingly share the feature
      of being basic peptides that, once released by HIV(+) cells, bind to polyanionic
      heparan sulfate proteoglycans (HSPGs) on target uninfected cells, contributing to
      the onset of AIDS-associated pathologies. To identify multitarget anti-HIV
      prodrugs, we investigated the gp120 and Tat antagonist potentials of a series of
      polyanionic synthetic sulfonic acid polymers (SSAPs). Surface plasmon resonance
      revealed that SSAPs inhibit with a competitive mechanism of action the binding of
      Tat and gp120 to surface-immobilized heparin, an experimental condition that
      resembles binding to cellular HSPGs. Accordingly, SSAPs inhibited HSPG-dependent
      cell internalization and the transactivating activity of Tat. Little is known
      about the binding of free gp120 to target cells. Here, we identified two classes
      of gp120 receptors expressed on endothelial cells, one of which was consistent
      with an HSPG-binding, low-affinity/high-capacity receptor that is inhibited by
      free heparin. SSAPs inhibited the binding of free gp120 to endothelial cells, as
      well as its capacity to induce apoptosis in the same cells. In all the assays,
      poly(4-styrenesulfonic acid) (PSS) proved to be the most potent antagonist of Tat
      and gp120. Accordingly, PSS bound both proteins with high affinity. In
      conclusion, SSAPs represent an interesting class of compounds that bind both
      gp120 and Tat and inhibit their HSPG-dependent cell surface binding and
      pathological effects. As these activities contribute to both AIDS progression and
      associated pathologies, SSAPs can be considered prototypic molecules for the
      development of multitarget drugs for the treatment of HIV infection and AIDS
      associated pathologies.

PMID- 17452492
TI  - Predicting pediatric distress during radiation therapy procedures: the role of
      medical, psychosocial, and demographic factors.
AB  - OBJECTIVES: The purpose of this work was to identify demographic, medical, and
      psychosocial variables that predict radiation therapy-related distress among
      pediatric patients with cancer. PATIENTS AND METHODS: Seventy-nine children
      between the ages of 2 and 7 years were consecutively enrolled in the study.
      Radiation therapy-related distress was measured by rates of anesthesia, observed
      behavioral distress, and heart rate. RESULTS: Younger age and higher observed
      behavioral distress predicted the use of anesthesia, higher baseline heart rate
      predicted lower initial observed behavioral distress, and prone treatment
      position was associated with increases in both observed behavioral distress and
      heart rate relative to baseline. CONCLUSIONS: Modifiable treatment and
      psychological variables directly relate to pediatric radiation therapy-related
      distress. Implementation of developmentally appropriate and cost-effective
      interventions to reduce procedural radiation therapy distress is warranted.

PMID- 17452493
TI  - Hospital-based directly observed therapy for HIV-infected children and
      adolescents to assess adherence to antiretroviral medications.
AB  - BACKGROUND: The introduction of highly active antiretroviral therapy for HIV led
      to significant declines in HIV-associated morbidity and mortality in children.
      Nonadherence to antiretroviral therapy is the leading cause of treatment failure
      in HIV-infected patients. The ability to recognize nonadherence is suboptimal,
      and differentiating it from other causes of inadequate viral suppression may be
      difficult. OBJECTIVES: The purpose of this work was to examine the efficacy of
      hospital-based directly observed therapy in assessing adherence to antiretroviral
      medications in HIV-infected children and adolescents suspected of nonadherence
      and failing other interventions. METHODS: The medical charts of all HIV-infected
      patients admitted to the University of Chicago Comer Children's Hospital for
      directly observed therapy from July 2004 to June 2006 were reviewed. Patients
      were hospitalized for 7 days. Data collected included demographics, clinical and
      immune class category, previous and current antiretroviral medications, viral
      resistance tests, HIV-1 RNA viral load, and CD4+ T-cell number and percentage
      before and after directly observed therapy. RESULTS: There were 9 perinatally
      infected patients with a total of 13 admissions. The median age was 13 years, and
      8 had been treated with multiple antiretroviral regimens. Three common patterns
      of changes in the viral load over time were observed. In the first, the viral
      load dropped at the end of the directly observed therapy period and stayed low
      thereafter. In the second, the drop in the viral load seen at the end of the
      period was not sustained. In the third, there was no change in the viral load
      during or after the directly observed therapy period. Compared with the viral
      load at admission, the viral load at the end of directly observed therapy was
      lower in 8 patients with a mean +/- SD decrease of 0.8 +/- 0.55 log10 copies per
      mL. CONCLUSIONS: Short, hospital-based directly observed therapy was helpful in
      confirming nonadherence to antiretroviral medications, therefore impacting future
      therapeutic decisions in HIV-infected children and adolescents. Short, hospital
      based directly observed therapy should be considered in patients with poor
      virological control for whom outpatient interventions have failed.

PMID- 17452494
TI  - Serotonin inhibits neuronal excitability by activating two-pore domain k+
      channels in the entorhinal cortex.
AB  - The entorhinal cortex (EC) is regarded as the gateway to the hippocampus; the
      superficial layers (layers I-III) of the EC convey the cortical input projections
      to the hippocampus, whereas deep layers of the EC relay hippocampal output
      projections back to the superficial layers of the EC or to other cortical
      regions. The superficial layers of the EC receive strong serotonergic projections
      from the raphe nuclei. However, the function of serotonin in the EC is still
      elusive. In the present study, we examined the molecular and cellular mechanisms
      underlying serotonin-mediated inhibition of the neuronal excitability in the
      superficial layers (layers II and III) of the EC. Application of serotonin
      inhibited the excitability of stellate and pyramidal neurons in the superficial
      layers of the EC by activating the TWIK-1 type of the two-pore domain K(+)
      channels. The effects of 5-HT were mediated via 5-HT(1A) receptors and required
      the function of Galpha(i3) subunit and protein kinase A. Serotonin-mediated
      inhibition of EC activity resulted in an inhibition of hippocampal function. Our
      study provides a cellular mechanism that might at least partially explain the
      roles of serotonin in many physiological functions and neurological diseases.

PMID- 17452495
TI  - Structure-activity relationship of 1,4-dihydropyridines as potentiators of the
      cystic fibrosis transmembrane conductance regulator chloride channel.
AB  - Mutations occurring in the CFTR gene, encoding for the cystic fibrosis
      transmembrane conductance regulator chloride channel, cause cystic fibrosis (CF).
      Mutations belonging to class II, such as DeltaPhe508, give rise to a protein with
      both a defective maturation and altered channel gating. Mutations belonging to
      class III, such as G551D and G1349D, cause only a gating defect. We have
      previously identified antihypertensive 1,4-dihydropyridines (DHPs), a class of
      drugs that block voltage-dependent Ca(2+) channels, as effective potentiators of
      CFTR gating, able to correct the defective activity of CFTR mutants (Mol
      Pharmacol 68:1736-1746, 2005). However, optimization of potency for CFTR versus
      Ca(2+) channels is required to design selective compounds for CFTR
      pharmacotherapy. In the present study, we have established DHP structure-activity
      relationship for both CFTR potentiation and Ca(2+) channel inhibition using cell
      based assays for both types of channels. A panel of 333 felodipine analogs was
      studied to understand the effect of various substitutions and modifications in
      the DHP scaffold. Our results show that alkyl substitutions at the para position
      of the 4-phenyl ring lead to compounds with very low activity on Ca(2+) channels
      and strong effect as potentiators on the DeltaPhe508, G551D, and G1349D CFTR
      mutants.

PMID- 17452496
TI  - Site-specific inhibition of glomerulonephritis progression by targeted delivery
      of dexamethasone to glomerular endothelium.
AB  - Glomerulonephritis represents a group of renal diseases with glomerular
      inflammation as a common pathologic finding. Because of the underlying
      immunologic character of these disorders, they are frequently treated with
      glucocorticoids and cytotoxic immunosuppressive agents. Although effective, use
      of these compounds has limitations as a result of toxicity and systemic side
      effects. In the current study, we tested the hypothesis that targeted delivery of
      dexamethasone (dexa) by immunoliposomes to activated glomerular endothelium
      decreases renal injury but prevents its systemic side effects. E-selectin was
      chosen as a target molecule based on its disease-specific expression on activated
      glomerular endothelium in a mouse anti-glomerular basement membrane
      glomerulonephritis. Site-selective delivery of Ab(Esel) liposome-encapsulated
      dexamethasone strongly reduced glomerular proinflammatory gene expression without
      affecting blood glucose levels, a severe side effect of administration of free
      dexamethasone. Dexa-Ab(Esel) liposomes reduced renal injury as shown by a
      reduction of blood urea nitrogen levels, decreased glomerular crescent formation,
      and down-regulation of disease-associated genes. Immunoliposomal drug delivery to
      glomerular endothelium presents a powerful new strategy for treatment of
      glomerulonephritis to sustain efficacy and prevent side effects of potent anti
      inflammatory drugs.

PMID- 17452498
TI  - Differential effects of 17beta-estradiol on function and expression of estrogen
      receptor alpha, estrogen receptor beta, and GPR30 in arteries and veins of
      patients with atherosclerosis.
AB  - Venous complications have been implicated in the adverse effects of hormone
      replacement therapy. This study investigated acute effects of the natural
      estrogen, 17beta-estradiol, on function, estrogen receptors/GPR30 expression, and
      kinase activation in vascular rings and cultured smooth muscle cells from
      arteries and veins of patients with coronary artery disease. Changes in vascular
      tone of internal mammary arteries and saphenous veins exposed to the steroid were
      recorded. 17Beta-estradiol caused concentration-dependent, endothelium
      independent relaxation in arteries (P<0.05 versus solvent control) but not in
      veins (P not significant). 17Beta-estradiol enhanced contractions to endothelin-1
      in veins but not in arteries. The novel membrane estrogen receptor GPR30 was
      detected in both vessels. Moreover, gene expression of estrogen receptor beta was
      10-fold higher than that of estrogen receptor alpha or GPR30 (P<0.05). Expression
      of all 3 of the receptors was reduced after exposure to 17beta-estradiol in
      arteries but not in veins (P<0.05). Basal phosphorylation levels of extracellular
      signal-regulated kinase were higher in venous than in arterial smooth muscle
      cells and were increased by 17beta-estradiol in arterial cells only. In summary,
      this is the first study to report that, in human arteries but not in veins,
      17beta-estradiol acutely affects vascular tone, estrogen receptor expression,
      including GPR30, and extracellular signal-regulated kinase phosphorylation. These
      data indicate that effects of natural estrogens in humans differ between arterial
      and venous vascular beds, which may contribute to the vascular risks associated
      with menopause or hormone therapy.

PMID- 17452499
TI  - Proinflammatory profile within the grossly normal aged human aortic wall.
AB  - Studies in animal models demonstrate that angiotensin II and its downstream
      signaling molecules, that is, matrix metalloproteinases and monocyte
      chemoattractant protein-1, increase within the diffusely thickened intima of
      central arteries with aging. Whether such age-related changes occur within the
      human arterial wall is unknown. We harvested "grossly normal thoracic aortas"
      from 5 young (20+/-3 years) and 5 old white males (65+/-6 years) at necropsy,
      after death from traumatic causes. The intimae of older samples were markedly and
      diffusely thickened compared with younger intimae and contained increased levels
      of angiotensin-converting enzyme, angiotensin II, angiotensin II receptor type 1,
      matrix metalloproteinases 2/9, monocyte chemoattractant protein-1, and collagen I
      and III proteins. In situ activities of metalloproteinases 2/9 were also
      significantly enhanced within old, normal aortas. The thickened intima of older
      aortas also contained a 5-fold increase in the embryonic form of smooth muscle
      myosin heavy chain-labeled cells than that of younger aortas, and these fetal
      type cells were colocalized with angiotensin II protein staining. The ability of
      isolated smooth muscle cells to invade an artificial basement membrane in
      response to a monocyte chemoattractant protein-1 gradient increased with age.
      Furthermore, angiotensin II increased the invasive capacity of young smooth
      muscle cells, and this effect was reduced by a metalloproteinase inhibitor or an
      angiotensin II receptor blocker. Thus, in the absence of lipid infiltration, the
      aged human aortic wall exhibits a proinflammatory profile that renders it a
      fertile substrate for the development of arterial disease, for example,
      atherosclerosis and hypertension.

PMID- 17452500
TI  - Modifications of arterial phenotype in response to amine oxidase inhibition by
      semicarbazide.
AB  - Semicarbazide-sensitive amine oxidase (SSAO)-deficient mice present no alteration
      in elastin cross-linking processes and carotid mechanical properties. In
      contrast, previous studies have shown that SSAO inhibitors induced marked
      anomalies in arterial structure and function. The aim of the present study was to
      examine the effect of semicarbazide (SCZ), an efficient SSAO inhibitor, on the
      arterial phenotype of the carotid artery in relation to modulation of SSAO and
      lysyl oxidase activities in growing rats. We first show that after 6 weeks of SCZ
      treatment (100 mg/kg per day), SSAO activity was reduced by 90%, whereas lysyl
      oxidase activity was only partially inhibited (<60%) in carotid artery, compared
      with controls. There was significant growth inhibition and no difference in mean
      arterial pressure but an increase in pulse pressure with a smaller arterial
      diameter in SCZ-treated rats. SCZ decreased aortic insoluble elastin without a
      change in total collagen. In addition, extracellular proteins other than
      insoluble elastin and collagen were increased in SCZ-treated rats. All of the
      elastic lamellae presented globular masses along their periphery, and focal
      disorganization was observed in the ascending aorta. Carotid artery mechanical
      strength was lower in SCZ-treated rats, and the elastic modulus-wall stress curve
      was shifted leftward compared with controls, indicating increased stiffness.
      Thus, SCZ modifies arterial geometry and mechanical properties, alters elastic
      fiber structure, and reduces the content of cross-linked elastin. Because these
      abnormalities are essentially absent in SSAO-deficient mice, our results suggest
      that lysyl oxidase inhibition is responsible for the major part of the vascular
      phenotype of SCZ-treated rats.

PMID- 17452501
TI  - Heparin impairs glycocalyx barrier properties and attenuates shear dependent
      vasodilation in mice.
AB  - The endothelial glycocalyx is a hydrated mesh of polysaccharides and adsorbed
      plasma proteins that forms the true interface between the flowing blood and the
      endothelium. We hypothesized in the present study that competitive binding of
      heparin to glycocalyx-associated proteins would affect glycocalyx barrier
      properties and mechanotransduction of shear stress to the endothelium. In
      anesthetized mice, the clearance of 70-kDa dextrans from the circulation was
      increased (P<0.05 versus saline) 1 hour after heparin (1.25 U) and glycocalyx
      degradation with hyaluronidase (35 U; amount cleared in 30 minutes after saline:
      11+/-5%; after heparin: 45+/-8%; after hyaluronidase: 30+/-3%). Clearance of 40
      kDa dextrans increased (P<0.05 versus saline) to a lesser extent after both
      treatments (saline: 46+/-3%; heparin: 60+/-5%; hyaluronidase: 60+/-2%). The
      dilator response of second-order arterioles in cremaster muscle during reactive
      hyperemia was reduced for < or =90 minutes after heparin as reflected by a
      decrease (P=0.008) in t(50) of diameter recovery, and this effect was associated
      with a diminished NO bioavailability. Infusion of hyaluronidase resulted in
      reductions (P<0.05) in baseline and peak reactive hyperemic diameter, whereas,
      despite an increase in wall shear rate at the beginning of reactive hyperemia,
      t(50) of diameter recovery was not affected. In conclusion, our data in mice show
      that a heparin challenge is associated with increased vascular leakage of
      dextrans and impaired arteriolar vasodilation during reactive hyperemia. Our data
      suggest that protein-heparan sulfate interactions are important for a functional
      glycocalyx.

PMID- 17452502
TI  - Long-term prognostic value of blood pressure variability in the general
      population: results of the Pressioni Arteriose Monitorate e Loro Associazioni
      Study.
AB  - The hypothesis has been advanced that cardiovascular prognosis is related not
      only to 24-hour mean blood pressure but also to blood pressure variability. Data,
      however, are inconsistent, and no long-term prognostic study is available. In
      2012 individuals randomly selected from the population of Monza (Milan), 24-hour
      ambulatory blood pressure (Spacelabs 90207) was measured via readings spaced by
      20 minutes. Systolic and diastolic blood pressure variability was obtained by
      calculating the following: (1) the SD of 24-hour, day, and night mean values; (2)
      the day-night blood pressure difference; and (3) the residual or erratic blood
      pressure variability (Fourier spectral analysis). Fatal cardiovascular and
      noncardiovascular events were registered for 148 months. When adjusted for age,
      sex, 24-hour mean blood pressure, and other risk factors, there was no
      relationship between the risk of death and 24-hour, day, and night blood pressure
      SDs. In contrast, the adjusted risk of cardiovascular death was inversely related
      to day-night diastolic BP difference (beta coefficient=-0.040; P<0.02) and showed
      a significant positive relationship with residual diastolic blood pressure
      variability (beta coefficient=0.175; P<0.002). Twenty-four-hour mean blood
      pressure attenuation of nocturnal hypotension and erratic diastolic blood
      pressure variability all independently predicted the mortality risk, with the
      erratic variability being the most important factor. Our data show that the
      relationship of blood pressure to prognosis is complex and that phenomena other
      than 24-hour mean values are involved. They also provide the first evidence that
      short-term erratic components of blood pressure variability play a prognostic
      role, with their increase being accompanied by an increased cardiovascular risk.

PMID- 17452503
TI  - Hypoadiponectinemia: a novel link between obesity and hypertension?

PMID- 17452504
TI  - Hypoadiponectinemia as a predictor for the development of hypertension: a 5-year
      prospective study.
AB  - Low circulating levels of adiponectin, an adipokine with insulin-sensitizing,
      antiatherogenic, and anti-inflammatory properties, are found in hypertensive
      patients. Adiponectin replenishment ameliorated hypertension in adiponectin
      deficient mice or obese, hypertensive mice with hypoadiponectinemia, suggesting
      an etiologic role of adiponectin in hypertension. We aimed to determine, in this
      5-year prospective study, whether hypoadiponectinemia could predict the
      development of hypertension in a nondiabetic Chinese cohort. A total of 577
      subjects (249 men and 328 women) were recruited from the population-based Hong
      Kong Cardiovascular Risk Factor Prevalence Study and prospectively followed up
      for 5 years. The relationship of serum adiponectin with the development of
      hypertension (sitting blood pressure >or=140/90 mm Hg) was investigated in a
      nested case-control study consisting of 70 subjects who had developed
      hypertension on follow-up and 140 age- and sex-matched control subjects who were
      normotensive both at baseline and at year 5. At baseline, serum adiponectin level
      in the lowest sex-specific tertile was more likely to be associated with
      hypertension (P=0.003 versus the highest tertile, after adjusting for age, body
      mass index, fasting insulin, and high-sensitivity C-reactive protein). At year 5,
      baseline serum adiponectin was a significant independent predictor of incident
      hypertension in the nested case-control study (P=0.015; age adjusted), together
      with mean arterial pressure (P<0.001), high-sensitivity C-reactive protein
      (P=0.018), and body mass index (P=0.004). Normotensive subjects with baseline
      serum adiponectin levels in the lowest sex-specific tertile had an increased risk
      of becoming hypertensive (adjusted odds ratio: 2.76; 95% CIs: 1.06 to 7.16;
      P=0.037 versus highest tertile). Our data suggest that hypoadiponectinaemia may
      be involved in the pathogenesis of hypertension in humans.

PMID- 17452505
TI  - Long-term trandolapril treatment is associated with reduced aortic stiffness: the
      prevention of events with angiotensin-converting enzyme inhibition hemodynamic
      substudy.
AB  - The Prevention of Events with Angiotensin Converting Enzyme inhibition (PEACE)
      trial evaluated angiotensin-converting enzyme inhibition with trandolapril versus
      placebo added to conventional therapy in patients with stable coronary disease
      and preserved left ventricular function. The PEACE hemodynamic substudy evaluated
      effects of trandolapril on pulsatile hemodynamics. Hemodynamic studies were
      performed in 300 participants from 5 PEACE centers a median of 52 months (range,
      25 to 80 months) after random assignment to trandolapril at a target dose of 4 mg
      per day or placebo. Central pulsatile hemodynamics and carotid-femoral pulse wave
      velocity were assessed by using echocardiography, tonometry of the carotid and
      femoral arteries, and body surface transit distances. Patients randomly assigned
      to trandolapril tended to be older (mean+/-SD: 64.2+/-7.9 versus 62.9+/-7.7
      years; P=0.14), with a higher body mass index (28.5+/-4.0 versus 27.8+/-3.9
      kg/m(2); P=0.09) and lower ejection fraction (57.1+/-8.1% versus 58.7+/-8.4%;
      P<0.01). At the time of the hemodynamic substudy, the trandolapril group had
      lower mean arterial pressure (93.1+/-10.2 versus 96.3+/-11.3 mm Hg; P<0.01) and
      lower carotid-femoral pulse wave velocity (geometric mean [95% CI]: 10.4 m/s
      [10.0 to 10.9 m/s] versus 11.2 m/s [10.7 to 11.8 m/s]; P=0.02). The difference in
      carotid-femoral pulse wave velocity persisted (P<0.01) in an analysis that
      adjusted for baseline characteristics and follow-up mean pressure. In contrast,
      there was no difference in aortic compliance, characteristic impedance,
      augmentation index, or total arterial compliance. Angiotensin-converting enzyme
      inhibition with trandolapril produced a modest reduction in carotid-femoral pulse
      wave velocity, a measure of aortic wall stiffness, beyond what would be expected
      from blood pressure lowering or differences in baseline characteristics alone.

PMID- 17452506
TI  - Childhood growth and hypertension in later life.
AB  - Few studies have examined the effects of both prenatal and postnatal growth on
      hypertension. We report on hypertension in 2003 people aged 62 years who were
      randomly selected from the Helsinki birth cohort and examined in a clinic. Their
      heights and weights had been recorded serially up to age 11 years. A total of 644
      had already been diagnosed with hypertension. Compared with normotensive people,
      they were obese and insulin resistant. At birth they were thin and short, and
      they gained weight slowly up to age 2 years; thereafter they grew rapidly so that
      at age 11 years their body size was around the average. The odds ratio associated
      with each kilogram of birthweight was 0.42 (95% CI: 0.32 to 0.56); with each 10
      kg of current weight it was 1.85 (95% CI: 1.66 to 2.05). The blood pressures of
      another 802 people were classified as hypertensive under current definitions.
      They were overweight and had an atherogenic lipid profile. At birth they were
      short, and after birth they grew slowly so that at age 11 years they were short
      and thin. The odds ratio associated with each kilogram of weight at age 2 years
      was 0.75 (95% CI: 0.68 to 0.84); with each 10 kg of current weight it was 1.42
      (95% CI: 1.28 to 1.57). We conclude that 2 different paths of childhood growth
      precede the development of hypertension. We suggest that they lead to
      hypertension through different biological mechanisms and may respond differently
      to medication.

PMID- 17452507
TI  - Angiotensin-converting enzyme I/D and alpha-adducin Gly460Trp polymorphisms: from
      angiotensin-converting enzyme activity to cardiovascular outcome.
AB  - The angiotensin-converting enzyme (ACE) I/D and the alpha-adducin (ADD1)
      Gly460Trp polymorphisms are associated with cardiovascular risk factors. In a
      prospective population study and in cell models, we investigated the combined
      effects of these 2 polymorphisms. We randomly recruited 1287 white subjects
      (women: 50.0%; mean age: 55.9 years). We obtained outcomes from registries and
      repeat examinations (median 3). Over 9.0 years (median), 178 fatal or nonfatal
      cardiovascular events occurred. In ADD1 Trp allele carriers, the multivariate
      adjusted hazard ratios associated with ACE DD versus I were 1.72 (P=0.007) for
      total mortality, 2.35 (P=0.02) for cardiovascular mortality, 2.02 (P=0.005) for
      all cardiovascular events, and 2.59 (P=0.03) for heart failure. In contrast,
      these hazard ratios did not reach significance in ADD1 GlyGly homozygotes
      (0.08<or=P<or=0.90). The positive predictive value and attributable risk
      associated with ACE DD homozygosity combined with mutated ADD1 were 36.2% and
      10.3%, respectively. To clarify our epidemiological observations, we investigated
      the effects of mutated human ADD1 on the membrane-bound ACE activity in
      fibroblasts from 51 volunteers and in transfected human embryonic kidney cells
      (31 experiments). In fibroblasts (5.10 versus 3.63 nanomoles of generated
      hippuric acid per milligram of protein per minute; P=0.0021) and human embryonic
      kidney cells (1.086 versus 0.081 nmol/mg per minute; P=0.017), the membrane-bound
      ACE activity increased in the presence but not absence of the ADD1 Trp allele. In
      conclusion, the combination of ACE DD homozygosity and mutated ADD1 worsened
      cardiovascular prognosis to a similar extent as classic risk factors, possibly
      because of increased membrane-bound ACE activity in subjects carrying the ADD1
      Trp allele.

PMID- 17452508
TI  - Recent advances in arterial stiffness and wave reflection in human hypertension.

PMID- 17452509
TI  - Is angiotensin II a direct mediator of left ventricular hypertrophy? Time for
      another look.

PMID- 17452510
TI  - Natriuretic peptides: update on Peptide release, bioactivity, and clinical use.

PMID- 17452511
TI  - Risk of tearing the intact anterior cruciate ligament in the contralateral knee
      and rupturing the anterior cruciate ligament graft during the first 2 years after
      anterior cruciate ligament reconstruction: a prospective MOON cohort study.
AB  - BACKGROUND: The risk of tear of the intact anterior cruciate ligament in the
      contralateral knee after anterior cruciate ligament reconstruction of the
      opposite knee and the incidence of rupturing the anterior cruciate ligament graft
      during the first 2 years after surgery have not been extensively studied in a
      prospective manner. Clinicians have hypothesized that the opposite normal knee is
      at equal or increased risk compared with the risk of anterior cruciate ligament
      graft rupture in the operated knee. HYPOTHESIS: The risk of anterior cruciate
      ligament graft rupture and contralateral normal knee anterior cruciate ligament
      rupture at 2-year follow-up is equal. STUDY DESIGN: Cohort study; Level of
      evidence, 2. METHODS: The Multicenter Orthopaedic Outcome Network (MOON) database
      of a prospective longitudinal cohort of anterior cruciate ligament
      reconstructions was used to determine the number of anterior cruciate ligament
      graft ruptures and tears of the intact anterior cruciate ligament in the
      contralateral knee at 2-year follow-up. Two-year follow-up consisted of a phone
      interview and review of operative reports. RESULTS: Two-year data were obtained
      for 235 of 273 patients (86%). There were 14 ligament disruptions. Of these, 7
      were tears of the intact anterior cruciate ligament in the contralateral knee
      (3.0%) and 7 were anterior cruciate ligament graft failures (3.0%). CONCLUSION:
      The contralateral normal knee anterior cruciate ligament is at a similar risk of
      anterior cruciate ligament tear (3.0%) as the anterior cruciate ligament graft
      after primary anterior cruciate ligament reconstruction (3.0%).

PMID- 17452512
TI  - The effects of common anti-inflammatory drugs on the healing rat patellar tendon.
AB  - BACKGROUND: Tendon injuries that occur at the osteotendinous junction are
      commonly seen in clinical practice and range from acute strain to rupture.
      Nonsteroidal anti-inflammatory drugs are often prescribed in the treatment of
      these conditions, but the effect that these agents may have on the healing
      response at the bone-tendon junction is unclear. HYPOTHESIS: In response to an
      acute injury at the osteotendinous junction, the healing patellar tendon will
      have inferior biomechanical properties with administration of anti-inflammatory
      drugs as compared with acetaminophen and control. STUDY DESIGN: Controlled
      laboratory study. METHODS: A total of 215 Sprague-Dawley rats underwent
      transection of the patellar tendon at the inferior pole of the patella, which was
      subsequently stabilized with a cerclage suture. The animals were then randomized
      into 7 groups and administered 1 of the following analgesics for 14 days:
      ibuprofen, acetaminophen, naproxen, piroxicam, celecoxib, valdecoxib, or control.
      At 14 days, all animals were sacrificed, and the extensor mechanism was isolated
      and loaded to failure. Biochemical analysis of the repair site tissue was
      performed. Animal activity throughout the study was monitored using a
      photoelectric sensor system. RESULTS: The control group demonstrated greater
      maximum load compared with the celecoxib, valdecoxib, and piroxicam groups (P <
      .05). The acetaminophen and ibuprofen groups were also significantly stronger
      than the celecoxib group (P < .05) but not statistically different than the
      control group. A total of 23 specimens had failure of the cerclage suture with
      the following distribution: control (0/23), ibuprofen (0/23), acetaminophen
      (0/24), naproxen (3/24), piroxicam (4/24), celecoxib (6/22), and valdecoxib
      (10/24). The difference in distribution of the failures was significant (P <
      .001). CONCLUSIONS: Anti-inflammatory drugs, with the exception of ibuprofen, had
      a detrimental effect on healing strength at the bone-tendon junction as
      demonstrated by decreased failure loads and increased failures of the cerclage
      suture. Acetaminophen had no effect on healing strength. The biomechanical
      properties paralleled closely with the total collagen content at the injury site,
      suggesting that these agents may alter healing strength by decreasing collagen
      content. CLINICAL RELEVANCE: Selective and nonselective cyclooxygenase (COX)
      inhibitors should be used judiciously in the acute period after injury or
      surgical repair at the bone-tendon junction.

PMID- 17452513
TI  - Can a double-row anchorage technique improve tendon healing in arthroscopic
      rotator cuff repair?: A prospective, nonrandomized, comparative study of double
      row and single-row anchorage techniques with computed tomographic arthrography
      tendon healing assessment.
AB  - BACKGROUND: Increasing the rate of watertight tendon healing has been suggested
      as an important criterion for optimizing clinical results in rotator cuff
      arthroscopic repair. HYPOTHESIS: A double-row anchorage technique for rotator
      cuff repair will produce better clinical results and a better rate of tendon
      healing than a single-row technique. STUDY DESIGN: Cohort study; Level of
      evidence, 2. METHODS: We compared 31 patients undergoing surgery with a double
      row anchorage technique using Panalok anchors and Cuff Tack anchors and 35
      patients with rotator cuff tear undergoing surgery with a single-row anchorage
      arthroscopic technique using Panalok anchors. We compared pre- and postoperative
      Constant score and tendon healing, as evaluated by computed tomographic
      arthrography 6 months after surgery, in these 2 groups. RESULTS: The Constant
      score increased significantly in both groups, with no difference between the 2
      groups (P = .4). Rotator cuff healing was judged anatomic in 19 patients with
      double-row anchorage and in 14 patients with single-row anchorage; this
      difference between the groups was significant (P = .03). CONCLUSION: In this
      first study comparing double- and single-row anchorage techniques, we found no
      significant difference in clinical results, but tendon healing rates were better
      with the double-row anchorage. Improvements in the double-row technique might
      lead to better clinical and tendon healing results.

PMID- 17452514
TI  - The epidemiology of shoulder injuries in English professional rugby union.
AB  - BACKGROUND: Shoulder injuries constitute a considerable risk to professional
      rugby union players; however, there is a shortage of detailed epidemiologic
      information about injuries in this population. PURPOSE: To describe the
      incidence, severity, and risk factors associated with shoulder injuries in
      professional rugby union. STUDY DESIGN: Descriptive epidemiology study. METHOD:
      Medical personnel prospectively reported time-loss injuries in professional rugby
      union in England, and the shoulder injuries were evaluated. RESULTS: The
      incidence of shoulder injuries was significantly lower during training (0.10/1000
      player-training hours) compared with matches (8.9/1000 player-match hours). The
      most common match injury was acromioclavicular joint injury (32%); the most
      severe was shoulder dislocation and instability (mean severity, 81 days absent),
      which also caused the greatest proportion of absence (42%) and had the highest
      rate of recurrence (62%). The majority of match shoulder injuries were sustained
      in the tackle (65%), and outside backs were the most likely to sustain an injury
      from tackling (2.4/1000 player-tackles). Injuries sustained during training were
      significantly more severe (61 days) than were those sustained during match play
      (27 days), and defensive training sessions carried the highest risk of injury
      (0.45/1000 player-hours; mean severity, 67 days). A mean of 241 player-days per
      club per season were lost to shoulder injuries. CONCLUSION: Results suggest the
      potential to reduce this injury burden by modifying training activities and
      implementing "pre-habilitation" strategies in an effort to minimize the risk of
      shoulder dislocation/instability.

PMID- 17452515
TI  - High-dose immunosuppressive therapy and autologous hematopoietic cell
      transplantation for severe systemic sclerosis: long-term follow-up of the US
      multicenter pilot study.
AB  - More effective therapeutic strategies are required for patients with poor
      prognosis systemic sclerosis (SSc). A phase 2 single-arm study of high-dose
      immunosuppressive therapy (HDIT) and autologous CD34-selected hematopoietic cell
      transplantation (HCT) was conducted in 34 patients with diffuse cutaneous SSc.
      HDIT included total body irradiation (800 cGy) with lung shielding,
      cyclophosphamide (120 mg/kg), and equine antithymocyte globulin (90 mg/kg).
      Neutrophil and platelet counts were recovered by 9 (range, 7 to 13) and 11
      (range, 7 to 25) days after HCT, respectively. Seventeen of 27 (63%) evaluable
      patients who survived at least 1 year after HDIT had sustained responses at a
      median follow-up of 4 (range, 1 to 8) years. There was a major improvement in
      skin (modified Rodnan skin score, -22.08; P < .001) and overall function
      (modified Health Assessment Questionnaire Disability Index, -1.03; P < .001) at
      final evaluation. Importantly, for the first time, biopsies confirmed a
      statistically significant decrease of dermal fibrosis compared with baseline (P <
      .001). Lung, heart, and kidney function, in general, remained clinically stable.
      There were 12 deaths during the study (transplantation-related, 8; SSc-related,
      4). The estimated progression-free survival was 64% at 5 years. Sustained
      responses including a decrease in dermal fibrosis were observed exceeding those
      previously reported with other therapies. HDIT and autologous HCT for SSc should
      be evaluated in a randomized clinical trial.

PMID- 17452516
TI  - TREM-1 ligand expression on platelets enhances neutrophil activation.
AB  - The triggering receptor expressed on myeloid cells 1 (TREM-1) plays an important
      role in the innate immune response related to severe infections and sepsis.
      Modulation of TREM-1-associated activation improves the outcome in rodent models
      for pneumonia and sepsis. However, the identity and occurrence of the natural
      TREM-1 ligands are so far unknown, impairing the further understanding of the
      biology of this receptor. Here, we report the presence of a ligand for TREM-1 on
      human platelets. Using a recombinant TREM-1 fusion protein, we demonstrate
      specific binding of TREM-1 to platelets. TREM-1-specific signals are required for
      the platelet-induced augmentation of polymorphonuclear leukocyte (PMN) effector
      functions (provoked by LPS). However, TREM-1 interaction with its ligand is not
      required for platelet/PMN complex formation, which is dependent on integrins and
      selectins. Taken together, the results indicate that the TREM-1 ligand is
      expressed by platelets, and the TREM-1/ligand interaction contributes to the
      amplification of LPS-induced PMN activation. Our results shed new light on our
      understanding of TREM-1 and its role in the innate inflammatory response in
      infections and might contribute to the development of future concepts to treat
      sepsis.

PMID- 17452517
TI  - The C-MYB locus is involved in chromosomal translocation and genomic duplications
      in human T-cell acute leukemia (T-ALL), the translocation defining a new T-ALL
      subtype in very young children.
AB  - The C-Myb transcription factor is essential for hematopoiesis, including in the T
      cell lineage. The C-Myb locus is a common site of retroviral insertional
      mutagenesis, however no recurrent genomic involvement has been reported in human
      malignancies. Here, we identified 2 types of genomic alterations involving the C
      MYB locus at 6q23 in human T-cell acute leukemia (T-ALL). First, we found a
      reciprocal translocation, t(6;7)(q23;q34), that juxtaposed the TCRB and C-MYB
      loci (n = 6 cases). Second, a genome-wide copy-number analysis by array-based
      comparative genomic hybridization (array-CGH) identified short somatic
      duplications that include C-MYB (MYB(dup), n = 13 cases of 84 T-ALL, 15%).
      Expression analysis, including allele-specific approaches, showed stronger C-MYB
      expression in the MYB-rearranged cases compared with other T-ALLs, and a
      dramatically skewed C-MYB allele expression in the TCRB-MYB cases, which suggests
      that a translocation-driven deregulated expression may overcome a cellular
      attempt to down-regulate C-MYB. Strikingly, profiling of the T-ALLs by clinical,
      genomic, and large-scale gene expression analyses shows that the TCRB-MYB
      translocation defines a new T-ALL subtype associated with a very young age for T
      cell leukemia (median, 2.2 years) and with a proliferation/mitosis expression
      signature. By contrast, the MYB(dup) alteration was associated with the
      previously defined T-ALL subtypes.

PMID- 17452518
TI  - JAK2 617V>F positive polycythemia rubra vera maintained by approximately 18
      stochastic stem-cell divisions per year, explaining age of onset by a single rate
      limiting mutation.
AB  - As the rates of most cancers are proportional to the fourth to fifth power of age
      ("log-log" behavior), it is widely believed that 5 to 6 independent mutations are
      necessary for malignant transformation. Conversely, the peak incidences of most
      cancers are similar to stem-cell mutation rates at single loci, implying only one
      rate-limiting mutation. Here, flow cytometrically measured red blood cells
      mutated at a selectively neutral locus, glycophorin A, allow observation of
      individual stem-cell differentiation events in a log-log malignancy, polycythemia
      rubra vera. Contrary to predictions from multistep models, the clone is driven by
      infrequent (< annual) and rare ( approximately 18 per year) differentiation
      events. These parameters imply that malignant stem cells have a modest selective
      advantage. Correspondingly minor, typically less than 20%, increases in
      stochastic self-renewal ratios are modeled to show that single mutations can
      result in the observed fourth power relationship with age. The conundrum between
      log-log behavior and mutation rate is thereby reconcilable, with the age of onset
      arising not from the requirement for multiple, independent mutations but from
      infrequent, stochastic stem-cell division rates and single mutations causing
      initially minor effects, but initiating a clone whose expected number increases
      successively with age--an "exponential phenotype."

PMID- 17452519
TI  - Increased frequencies of CD4+ CD25(high) regulatory T cells in acute dengue
      infection.
AB  - Dengue virus infection is an increasingly important tropical disease, causing 100
      million cases each year. Symptoms range from mild febrile illness to severe
      hemorrhagic fever. The pathogenesis is incompletely understood, but
      immunopathology is thought to play a part, with antibody-dependent enhancement
      and massive immune activation of T cells and monocytes/macrophages leading to a
      disproportionate production of proinflammatory cytokines. We sought to
      investigate whether a defective population of regulatory T cells (T reg cells)
      could be contributing to immunopathology in severe dengue disease.
      CD4(+)CD25(high)FoxP3(+) T reg cells of patients with acute dengue infection of
      different severities showed a conventional phenotype. Unexpectedly, their
      capacity to suppress T cell proliferation and to secrete interleukin-10 was not
      altered. Moreover, T reg cells suppressed the production of vasoactive cytokines
      after dengue-specific stimulation. Furthermore, T reg cell frequencies and also T
      reg cell/effector T cell ratios were increased in patients with acute infection.
      A strong indication that a relative rise of T reg cell/effector T cell ratios is
      beneficial for disease outcome comes from patients with mild disease in which
      this ratio is significantly increased (P < 0.0001) in contrast to severe cases (P
      = 0.2145). We conclude that although T reg cells expand and function normally in
      acute dengue infection, their relative frequencies are insufficient to control
      the immunopathology of severe disease.

PMID- 17452520
TI  - Regulation of AID expression in the immune response.
AB  - The B cell-specific enzyme activation-induced cytidine deaminase (AID) has been
      shown to be essential for isotype switching and affinity maturation of antibody
      genes during the immune response. Conversely, AID activity has also been linked
      to autoimmunity and tumorigenesis. Determining how AID expression is regulated in
      vivo is therefore central to understanding its role in health and disease. Here
      we use phylogenetic footprinting and high-resolution histone acetylation mapping
      to accurately demarcate AID gene regulatory boundaries. Based on this strategy,
      we identify a novel, positive regulatory element required for AID transcription.
      Furthermore, we generate two AID indicator mouse strains using bacterial
      artificial chromosomes that faithfully recapitulate endogenous AID expression.
      The first strain uses a green fluorescent protein reporter to identify B cells
      that actively express AID during the immune response. In the second strain, AID
      transcription affects the permanent expression of a yellow fluorescent protein
      reporter in post-germinal center and terminally differentiated lymphocytes. We
      demonstrate the usefulness of these novel strains by resolving recent
      contradictory observations on AID expression during B cell ontogeny.

PMID- 17452521
TI  - Mature natural killer cell and lymphoid tissue-inducing cell development requires
      Id2-mediated suppression of E protein activity.
AB  - The Id2 transcriptional repressor is essential for development of natural killer
      (NK) cells, lymphoid tissue-inducing (LTi) cells, and secondary lymphoid tissues.
      Id2 was proposed to regulate NK and LTi lineage specification from multipotent
      progenitors through suppression of E proteins. We report that NK cell progenitors
      are not reduced in the bone marrow (BM) of Id2(-/-) mice, demonstrating that Id2
      is not essential for NK lineage specification. Rather, Id2 is required for
      development of mature (m) NK cells. We define the mechanism by which Id2
      functions by showing that a reduction in E protein activity, through deletion of
      E2A, overcomes the need for Id2 in development of BM mNK cells, LTi cells, and
      secondary lymphoid tissues. However, mNK cells are not restored in the blood or
      spleen of Id2(-/-)E2A(-/-) mice, suggesting a role for Id2 in suppression of
      alternative E proteins after maturation. Interestingly, the few splenic mNK cells
      in Id2(-/-) and Id2(-/-)E2A(-/-) mice have characteristics of thymus-derived NK
      cells, which develop in the absence of Id2, implying a differential requirement
      for Id2 in BM and thymic mNK development. Our findings redefine the essential
      functions of Id2 in lymphoid development and provide insight into the dynamic
      regulation of E and Id proteins during this process.

PMID- 17452522
TI  - Expression of lymphotoxin-alphabeta on antigen-specific T cells is required for
      DC function.
AB  - During an immune response, activated antigen (Ag)-specific T cells condition
      dendritic cells (DCs) to enhance DC function and survival within the inflamed
      draining lymph node (LN). It has been difficult to ascertain the role of the
      tumor necrosis factor (TNF) superfamily member lymphotoxin-alphabeta
      (LTalphabeta) in this process because signaling through the LTbeta-receptor
      (LTbetaR) controls multiple aspects of lymphoid tissue organization. To resolve
      this, we have used an in vivo system where the expression of TNF family ligands
      is manipulated only on the Ag-specific T cells that interact with and condition
      Ag-bearing DCs. We report that LTalphabeta is a critical participant required for
      optimal DC function, independent of its described role in maintaining lymphoid
      tissue organization. In the absence of LTalphabeta or CD40L on Ag-specific T
      cells, DC dysfunction could be rescued in vivo via CD40 or LTbetaR stimulation,
      respectively, suggesting that these two pathways cooperate for optimal DC
      conditioning.

PMID- 17452523
TI  - Type I interferon signaling is required for activation of the inflammasome during
      Francisella infection.
AB  - Francisella tularensis is a pathogenic bacterium whose virulence is linked to its
      ability to replicate within the host cell cytosol. Entry into the macrophage
      cytosol activates a host-protective multimolecular complex called the
      inflammasome to release the proinflammatory cytokines interleukin (IL)-1beta and 
      18 and trigger caspase-1-dependent cell death. In this study, we show that
      cytosolic F. tularensis subspecies novicida (F. novicida) induces a type I
      interferon (IFN) response that is essential for caspase-1 activation,
      inflammasome-mediated cell death, and release of IL-1beta and -18. Extensive type
      I IFN-dependent cell death resulting in macrophage depletion occurs in vivo
      during F. novicida infection. Type I IFN is also necessary for inflammasome
      activation in response to cytosolic Listeria monocytogenes but not vacuole
      localized Salmonella enterica serovar Typhimurium or extracellular adenosine
      triphosphate. These results show the specific connection between type I IFN
      signaling and inflammasome activation, which are two sequential events triggered
      by the recognition of cytosolic bacteria. To our knowledge, this is the first
      example of the positive regulation of inflammasome activation. This connection
      underscores the importance of the cytosolic recognition of pathogens and
      highlights how multiple innate immunity pathways interact before commitment to
      critical host responses.

PMID- 17452526
TI  - Michael Rape interviewed by William A. Wells about the biology of destruction.
AB  - Michael Rape says that ubiquitination's diversity and adaptability makes it an
      ideal entry point for understanding vast swaths of biology.

PMID- 17452527
TI  - Ubiquitination of the peroxisomal import receptor Pex5p is required for its
      recycling.
AB  - Pex5p, which is the import receptor for peroxisomal matrix proteins harboring a
      type I signal sequence (PTS1), is mono- and polyubiquitinated in Saccharomyces
      cerevisiae. We identified Pex5p as a molecular target for Pex4p-dependent
      monoubiquitination and demonstrated that either poly- or monoubiquitination of
      the receptor is required for the ATP-dependent release of the protein from the
      peroxisomal membrane to the cytosol as part of the receptor cycle. Therefore, the
      energy requirement of the peroxisomal import pathway has to be extended by a
      second ATP-dependent step, namely receptor monoubiquitination.

PMID- 17452528
TI  - Three microtubule severing enzymes contribute to the "Pacman-flux" machinery that
      moves chromosomes.
AB  - Chromosomes move toward mitotic spindle poles by a Pacman-flux mechanism linked
      to microtubule depolymerization: chromosomes actively depolymerize attached
      microtubule plus ends (Pacman) while being reeled in to spindle poles by the
      continual poleward flow of tubulin subunits driven by minus-end depolymerization
      (flux). We report that Pacman-flux in Drosophila melanogaster incorporates the
      activities of three different microtubule severing enzymes, Spastin, Fidgetin,
      and Katanin. Spastin and Fidgetin are utilized to stimulate microtubule minus-end
      depolymerization and flux. Both proteins concentrate at centrosomes, where they
      catalyze the turnover of gamma-tubulin, consistent with the hypothesis that they
      exert their influence by releasing stabilizing gamma-tubulin ring complexes from
      minus ends. In contrast, Katanin appears to function primarily on anaphase
      chromosomes, where it stimulates microtubule plus-end depolymerization and Pacman
      based chromatid motility. Collectively, these findings reveal novel and
      significant roles for microtubule severing within the spindle and broaden our
      understanding of the molecular machinery used to move chromosomes.

PMID- 17452529
TI  - Regulation of the G2-M cell cycle progression by the ERK5-NFkappaB signaling
      pathway.
AB  - Elucidation of mechanisms regulating cell cycle progression is of fundamental
      importance for cell and cancer biology. Although several genes and signaling
      pathways are implicated in G1-S regulation, less is known regarding the
      mechanisms controlling cell cycle progression through G2 and M phases. We report
      that extracellular signal-regulated kinase 5 (ERK5), a member of the mitogen
      activated protein kinases, is activated at G2-M and required for timely mitotic
      entry. Stimulation of ERK5 activated nuclear factor kappaB (NFkappaB) through
      ribosomal S6 kinase 2 (RSK2)-mediated phosphorylation and degradation of IkappaB.
      Furthermore, selective inhibition of NFkappaB at G2-M phases substantially
      delayed mitotic entry and inhibited transcription of G2-M-specific genes,
      including cyclin B1, cyclin B2, Plk-1, and cdc25B. Moreover, inhibition of
      NFkappaB at G2-M diminished mitosis induced by constitutive activation of ERK5,
      providing a direct link between ERK5, NFkappaB, and regulation of G2-M
      progression. We conclude that a novel ERK5-NFkappaB signaling pathway plays a key
      role in regulation of the G2-M progression.

PMID- 17452530
TI  - The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is
      crucial for TLR signaling.
AB  - Toll-like receptors (TLRs) sense the presence of microbial and viral pathogens by
      signal transduction mechanisms that remain to be fully elucidated. A single point
      mutation (H412R) in the polytopic endoplasmic reticulum (ER)-resident membrane
      protein UNC93B abolishes signaling via TLR3, 7, and 9. We show that UNC93B
      specifically interacts with TLR3, 7, 9, and 13, whereas introduction of the point
      mutation H412R in UNC93B abolishes their interactions. We establish the physical
      interaction of the intracellular TLRs with UNC93B in splenocytes and bone marrow
      derived dendritic cells. Further, by expressing chimeric TLRs, we show that TLR3
      and 9 bind to UNC93B via their transmembrane domains. We propose that a physical
      association between UNC93B and TLRs in the ER is essential for proper TLR
      signaling.

PMID- 17452531
TI  - Mitochondrial permeabilization relies on BH3 ligands engaging multiple
      prosurvival Bcl-2 relatives, not Bak.
AB  - The Bcl-2 family regulates apoptosis by controlling mitochondrial integrity. To
      clarify whether its prosurvival members function by sequestering their Bcl-2
      homology 3 (BH3)-only ligands or their multidomain relatives Bak and Bax, we
      analyzed whether four prosurvival proteins differing in their ability to bind
      specific BH3 peptides or Bak could protect isolated mitochondria. Most BH3
      peptides could induce temperature-dependent cytochrome c release, but
      permeabilization was prevented by Bcl-x(L), Bcl-w, Mcl-1, or BHRF1. However,
      their protection correlated with the ability to bind Bak rather than the added
      BH3 peptide and could be overcome only by BH3 peptides that bind directly to the
      appropriate prosurvival member. Mitochondria protected by both Bcl-x(L)-like and
      Mcl-1 proteins were disrupted only by BH3 peptides that engage both. BH3-only
      reagents freed Bak from Bcl-x(L) and Mcl-1 in mitochondrial and cell lysates. The
      findings support a model for the control of apoptosis in which certain
      prosurvival proteins sequester Bak/Bax, and BH3-only proteins must neutralize all
      protective prosurvival proteins to allow Bak/Bax to induce mitochondrial
      disruption.

PMID- 17452532
TI  - Dissection of the pathway required for generation of vitamin A and for Drosophila
      phototransduction.
AB  - Dietary carotenoids are precursors for the production of retinoids, which
      participate in many essential processes, including the formation of the
      photopigment rhodopsin. Despite the importance of conversion of carotenoids to
      vitamin A (all-trans-retinol), many questions remain concerning the mechanisms
      that promote this process, including the uptake of carotenoids. We use the
      Drosophila visual system as a genetic model to study retinoid formation from beta
      carotene. In a screen for mutations that affect the biosynthesis of rhodopsin, we
      identified a class B scavenger receptor, SANTA MARIA. We demonstrate that SANTA
      MARIA functions upstream of vitamin A formation in neurons and glia, which are
      outside of the retina. The protein is coexpressed and functionally coupled with
      the beta, beta-carotene-15, 15'-monooxygenase, NINAB, which converts beta
      carotene to all-trans-retinal. Another class B scavenger receptor, NINAD,
      functions upstream of SANTA MARIA in the uptake of carotenoids, enabling us to
      propose a pathway involving multiple extraretinal cell types and proteins
      essential for the formation of rhodopsin.

PMID- 17452533
TI  - Coupling Ca2+ store release to Icrac channel activation in B lymphocytes requires
      the activity of Lyn and Syk kinases.
AB  - Activation of the B cell receptor complex in B lymphocytes causes Ca(2+) release
      from intracellular stores, which, in turn, activates ion channels known as Icrac.
      We investigated the mechanisms that link Ca(2+) store release to channel gating
      in DT40 B lymphocyte cell lines genetically manipulated to suppress the
      expression of several tyrosine kinases: Btk, Lyn, Syk, and the Blnk adaptor
      molecule. The simultaneous but not the independent suppression of Lyn and Syk
      expression prevents the activation of Icrac without interfering with thapsigargin
      sensitive Ca(2+) store release. Icrac activation by Ca(2+) is reversed in mutant
      cells by the homologous expression of the missing kinases. Pharmacological
      inhibition of kinase activity by LavendustinA and PP2 cause the same functional
      deficit as the genetic suppression of enzyme expression. Biochemical assays
      demonstrate that kinase activity is required as a tonic signal: targets must be
      phosphorylated to link Ca(2+) store release to Icrac gating. The action of
      kinases on Icrac activation does not arise from control of the expression level
      of the stromal interaction molecule 1 and Orai1 proteins.

PMID- 17452534
TI  - PtdIns(4,5)P2 turnover is required for multiple stages during clathrin- and actin
      dependent endocytic internalization.
AB  - The lipid phosphatidylinositol-4,5-bisphosphate (PtdIns[4,5]P(2)) appears to play
      an important role in endocytosis. However, the timing of its formation and
      turnover, and its specific functions at different stages during endocytic
      internalization, have not been established. In this study, Sla2 ANTH-GFP and Sjl2
      3GFP were expressed as functional fusion proteins at endogenous levels to
      quantitatively explore PtdIns(4,5)P(2) dynamics during endocytosis in yeast. Our
      results indicate that PtdIns(4,5)P(2) levels increase and decline in conjunction
      with coat and actin assembly and disassembly, respectively. Live-cell image
      analysis of endocytic protein dynamics in an sjl1Delta sjl2Delta mutant, which
      has elevated PtdIns(4,5)P(2) levels, revealed that the endocytic machinery is
      still able to assemble and disassemble dynamically, albeit nonproductively. The
      defects in the dynamic behavior of the various endocytic proteins in this double
      mutant suggest that PtdIns(4,5)P(2) turnover is required for multiple stages
      during endocytic vesicle formation. Furthermore, our results indicate that
      PtdIns(4,5)P(2) turnover may act in coordination with the Ark1/Prk1 protein
      kinases in stimulating disassembly of the endocytic machinery.

PMID- 17452535
TI  - Obesity, disability, and mortality: a puzzling link.

PMID- 17452536
TI  - Measuring drug burden: a step forward.

PMID- 17452537
TI  - The impact of continuous positive airway pressure on blood pressure in patients
      with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo
      controlled randomized trials.
AB  - BACKGROUND: Continuous positive airway pressure (CPAP) in patients with
      obstructive sleep apnea syndrome (OSAS) might lower blood pressure, but evidence
      from clinical studies is inconsistent, perhaps as a result of small sample size
      or heterogeneity in study design. This study aimed to assess whether CPAP reduces
      ambulatory blood pressure in patients with OSAS, to quantify the effect size with
      precision, and to identify trial characteristics associated with the greatest
      blood pressure reductions. METHODS: We identified randomized controlled trials of
      CPAP vs placebo in patients with OSAS specifically reporting 24-hour ambulatory
      mean blood pressure (MBP). RESULTS: We included a total of 572 patients from 12
      randomized controlled trials. According to a random-effects model, the pooled
      estimate of the effect of the CPAP intervention was a net decrease of 1.69 mm Hg
      in 24-hour MBP (95% confidence interval, -2.69 to -0.69). Statistical
      heterogeneity was moderate (I(2) = 41%). Predefined metaregression analyses
      estimated that 24-hour MBP would decrease by 0.89 mm Hg per 10-point increase in
      apnea-hypopnea index at entry (P = .006), by 0.74 mm Hg for each increase of 10
      arousal events per hour slept (P = .008), and by 1.39 mm Hg for each 1-hour
      increase in effective nightly use of the CPAP device (P = .01). CONCLUSIONS:
      Among patients with OSAS, CPAP reduces 24-hour ambulatory MBP, with greater
      treatment-related reductions in ambulatory MBP among patients with a more severe
      degree of OSAS and a better effective nightly use of the CPAP device. These
      reductions in blood pressure are likely to contribute to a better prognosis in
      terms of adverse cardiovascular events.

PMID- 17452538
TI  - Obesity and workers' compensation: results from the Duke Health and Safety
      Surveillance System.
AB  - BACKGROUND: Obese individuals have increased morbidity and use of health
      services. Less is known about the effect of obesity on workers' compensation. The
      objective of this study was to determine the relationship between body mass index
      (BMI) (calculated as weight in kilograms divided by height in meters squared) and
      number and types of workers' compensation claims, associated costs, and lost
      workdays. METHODS: Retrospective cohort study. Participants included 11 728
      health care and university employees (34 858 full-time equivalents [FTEs]) with
      at least 1 health risk appraisal between January 1, 1997, and December 31, 2004.
      The main outcome measures were stratified rates of workers' compensation claims,
      associated costs, and lost workdays, calculated by BMI, sex, age, race/ethnicity,
      smoking status, employment duration, and occupational group. The body part
      affected, nature of the illness or injury, and cause of the illness or injury
      were also investigated. Multivariate Poisson regression models examined the
      effects of BMI, controlling for demographic and work-related variables. RESULTS:
      There was a clear linear relationship between BMI and rate of claims. Employees
      in obesity class III (BMI >/=40) had 11.65 claims per 100 FTEs, while recommended
      weight employees had 5.80; the effect on lost workdays (183.63 vs 14.19 lost
      workdays per 100 FTEs), medical claims costs ($51 091 vs $7503 per 100 FTEs), and
      indemnity claims costs ($59 178 vs $5396 per 100 FTEs) was even stronger. The
      claims most strongly affected by BMI were related to the following: lower
      extremity, wrist or hand, and back (body part affected); pain or inflammation,
      sprain or strain, and contusion or bruise (nature of the illness or injury); and
      falls or slips, lifting, and exertion (cause of the illness or injury). The
      combination of obesity and high-risk occupation was particularly detrimental.
      CONCLUSIONS: Maintaining healthy weight not only is important to workers but
      should also be a high priority for their employers given the strong effect of BMI
      on workers' injuries. Complementing general interventions to make all workplaces
      safer, work-based programs targeting healthy eating and physical activity should
      be developed and evaluated.

PMID- 17452539
TI  - The effect of obesity on disability vs mortality in older Americans.
AB  - BACKGROUND: The association between obesity and mortality is reduced or
      eliminated in older subjects. In addition to mortality, disability is an
      important health outcome. The objectives of this study were to examine the
      association between body mass index (BMI), calculated as weight in kilograms
      divided by height in meters squared, and subsequent disability and mortality
      among older Americans, as well as to estimate the effect of BMI on life
      expectancy and disability-free life expectancy among older Americans. METHODS: We
      studied 8359 non-Hispanic white Americans, 1931 African Americans, and 2435
      Mexican Americans 65 years or older who were not disabled at baseline from 5
      sites of the Established Populations for Epidemiologic Studies of the Elderly.
      Measures included BMI, medical conditions, activities of daily living, and
      demographic information. Cox proportional hazards regression analysis was used to
      estimate the hazard ratios (HRs) for subsequent disability and mortality during 7
      years of follow-up. Total life expectancy and disability-free life expectancy
      were estimated using the interpolation of Markov chain approach. RESULTS: The
      lowest HR (1.02; 95% confidence interval [CI], 0.94-1.10) for disability was at a
      BMI of 25 to less than 30. Subjects with BMIs of lower than 18.5 or 30 or higher
      at baseline were significantly more likely to experience disability during the
      follow-up period. In contrast, the lowest HRs for mortality were seen among
      subjects with BMIs of 25 to less than 30 (HR, 0.78; 95% CI, 0.72-0.85) and 30 to
      less than 35 (HR, 0.80; 95% CI, 0.72-0.90), with subjects with BMIs of lower than
      25 or 35 or higher experiencing higher hazards for mortality. Disability-free
      life expectancy is greatest among subjects with a BMI of 25 to less than 30.
      CONCLUSION: Assessments of the effect of obesity on the health of older Americans
      should account for mortality and incidence of disability.

PMID- 17452540
TI  - A drug burden index to define the functional burden of medications in older
      people.
AB  - BACKGROUND: Older people carry a high burden of illness for which medications are
      indicated, along with increased risk of adverse drug reactions. We developed an
      index to determine drug burden based on pharmacologic principles. We evaluated
      the relationship of this index to physical and cognitive performance apart from
      disease indication. METHODS: Data from the Health, Aging, and Body Composition
      Study on 3075 well-functioning community-dwelling persons aged 70 to 79 years
      were analyzed by multiple linear regression to assess the cross-sectional
      association of drug burden index with a validated composite continuous measure
      for physical function, and with the Digit Symbol Substitution Test for cognitive
      performance. RESULTS: Use of anticholinergic and sedative medications was
      associated with poorer physical performance score (anticholinergic exposure, 2.08
      vs 2.21, P<.001; sedative exposure, 2.09 vs 2.19, P<.001) and cognitive
      performance on the Digit Symbol Substitution Test (anticholinergic exposure, 34.5
      vs 35.5, P = .045; sedative exposure, 34.0 vs 35.5, P = .01). Associations were
      strengthened when exposure was calculated by principles of dose response. An
      increase of 1 U in drug burden index was associated with a deficit of 0.15 point
      (P<.001) on the physical function scale and 1.5 points (P = .01) on the Digit
      Symbol Substitution Test. These values were more than 3 times those associated
      with a single comorbid illness. CONCLUSIONS: The drug burden index demonstrates
      that anticholinergic and sedative drug exposure is associated with poorer
      function in community-dwelling older people. This pharmacologic approach provides
      a useful evidence-based tool for assessing the functional effect of exposure to
      medications in this population.

PMID- 17452541
TI  - Cost-benefit analysis of a hospital pharmacy bar code solution.
AB  - BACKGROUND: Bar coding can reduce hospital pharmacy dispensing errors, but it is
      unclear if the benefits of this technology justify its costs. The purpose of this
      study was to assess the costs and benefits and determine the return on investment
      at the institutional level for implementing a pharmacy bar code system. METHODS:
      We performed a cost-benefit analysis of a bar code-assisted medication-dispensing
      system within a large, academic, nonprofit tertiary care hospital pharmacy. We
      took the implementing hospital's perspective for a 5-year horizon. The primary
      outcome was the net financial cost and benefit after 5 years. The secondary
      outcome was the time until total benefits equaled total costs. Single-variable, 2
      variable, and multiple-variable Monte Carlo sensitivity analyses were performed
      to test the stability of the outcomes. RESULTS: In inflation- and time value
      adjusted 2005 dollars, total costs during 5 years were $2.24 million ($1.31
      million in 1-time costs during the initial 3.5 years and $342 000 per year in
      recurring costs starting in year 3). The primary benefit was a decrease in
      adverse drug events from dispensing errors (517 events annually), resulting in an
      annual savings of $2.20 million. The net benefit after 5 years was $3.49 million.
      The break-even point for the hospital's investment occurred within 1 year after
      becoming fully operational. A net benefit was achieved within 10 years under
      almost all sensitivity scenarios. In the Monte Carlo simulation, the net benefit
      during 5 years was $3.2 million (95% confidence interval, -$1.2 million to $12.1
      million), and the break-even point for return on investment occurred after 51
      months (95% confidence interval, 30 to 180 months). CONCLUSION: Implementation of
      a bar code-assisted medication-dispensing system in hospital pharmacies can
      result in a positive financial return on investment for the health care
      organization.

PMID- 17452542
TI  - Migraine and risk of cardiovascular disease in men.
AB  - BACKGROUND: The vascular component of the migraine-specific physiologic profile
      and the observed adverse cardiovascular risk profile in migraineurs suggest an
      association between migraine and cardiovascular disease (CVD). In women, migraine
      has been associated with increased risk of CVD, including coronary events.
      Compatible data in men are lacking. METHODS: Prospective cohort study of 20 084
      men aged 40 to 84 years participating in the Physicians' Health Study. In yearly
      questionnaires, men were asked for information on migraine, risk factors, and the
      occurrence of study end points. We classified men as having migraine if they
      indicated migraine during the first 5 years, after which time follow-up began.
      Information on aura was not available. All the men were free of CVD at the start
      of follow-up. During a mean of 15.7 years, we followed up participants for the
      occurrence of a first major CVD event (nonfatal ischemic stroke, nonfatal
      myocardial infarction, or death from ischemic CVD). We also evaluated the
      individual end points, coronary revascularization, and angina. RESULTS: A total
      of 1449 men (7.2%) reported migraine, and during follow-up, 2236 major CVD events
      occurred. Compared with nonmigraineurs, men who reported migraine had
      multivariable-adjusted hazard ratios (95% confidence intervals) of 1.24 (1.06
      1.46; P = .008) for major CVD, 1.12 (0.84-1.50; P = .43) for ischemic stroke,
      1.42 (1.15-1.77; P<.001) for myocardial infarction, 1.05 (0.89-1.24; P = .54) for
      coronary revascularization, 1.15 (0.99-1.33; P = .068) for angina, and 1.07 (0.80
      1.43; P = .65) for ischemic cardiovascular death. CONCLUSION: In this large
      prospective cohort of apparently healthy men, migraine was associated with
      increased risk of major CVD, which was driven by increased risk of myocardial
      infarction.

PMID- 17452543
TI  - Longitudinal association between depressive symptoms and incident type 2 diabetes
      mellitus in older adults: the cardiovascular health study.
AB  - BACKGROUND: Prospective studies indicate that a single self-report of high
      depressive symptoms is associated with an increased risk of developing type 2
      diabetes mellitus. METHODS: We tested whether a single report of high depressive
      symptoms, an increase in depressive symptoms, or persistently high depressive
      symptoms over time were associated with the development of diabetes in adults 65
      years and older. Participants from the Cardiovascular Health Study completed the
      10-item Center for Epidemiological Studies-Depression Scale (CES-D) annually from
      1989 to 1999. A single report of high depressive symptoms (CES-D score, >/=8), an
      increase in symptoms during follow-up (>/=5 from baseline), and persistently high
      symptoms (2 consecutive scores >/=8) were each studied in relation to incident
      diabetes, defined by initiation of diabetes control medications among
      participants who were free from diabetes at baseline (n = 4681). RESULTS: The
      mean CES-D score at baseline was 4.5 (SD, 4.5). The incidence rate of diabetes
      was 4.4 per 1000 person-years. Following adjustment for baseline demographic
      characteristics and measures of physical activity, smoking, alcohol intake, body
      mass index, and C-reactive protein during follow-up, each measure of depressive
      symptoms was significantly associated with incident diabetes (high baseline CES-D
      score: hazard ratio, 1.6 [95% confidence interval, 1.1-2.3]; CES-D score
      increase: hazard ratio, 1.5 [95% confidence interval, 1.1-2.2]; and persistently
      high symptoms: hazard ratio, 1.5 [95% confidence interval, 1.1-2.3]). CONCLUSION:
      Older adults who reported higher depressive symptoms were more likely to develop
      diabetes than their counterparts; this association was not fully explained by
      risk factors for diabetes.

PMID- 17452544
TI  - Coronary angiography following acute myocardial infarction in Ontario, Canada.
AB  - BACKGROUND: The role of scientific evidence in shaping recommendations on
      capacity targets and cardiovascular technology utilization is unclear. METHODS:
      The temporal growth in the use of coronary angiography services and the use of
      statins after an acute myocardial infarction (AMI) was determined for all
      patients older than 65 years admitted to any hospital in Ontario, Canada, between
      1992 and 2004. A Bayesian change-point regression model was used to determine the
      rate of maximum uptake (inflection point) for use of cardiac catheterization
      service and statins after AMI. The inflection points were compared with the
      corresponding publication dates of the first positive evidence for outcome
      efficacy of use of cardiac catheterization service and statins after AMI as
      obtained from randomized control trials. RESULTS: The use of post-AMI coronary
      angiography closely mirrored overall temporal increases in cardiac
      catheterization capacity between 1992 and 2004 (r = 0.95, P<.001). The inflection
      point for post-AMI angiography service use was September 1998, 11 months before
      the publication of the first positive randomized controlled trial demonstrating
      benefit of routine post-AMI angiography. Conversely, the inflection point for
      statin therapy occurred in October 1998, 47 months after the publication of the
      first positive randomized controlled trial demonstrating the benefits of statin
      therapy for the secondary prevention of coronary artery disease. These findings
      were consistent regardless of the presence of on-site cardiac catheterization
      facilities at the admitting AMI institution and patient illness severity levels.
      CONCLUSION: The proliferation of cardiac catheterization in Ontario is
      attributable to factors other than the emergence of published scientific
      evidence.

PMID- 17452545
TI  - Induced and spontaneous abortion and incidence of breast cancer among young
      women: a prospective cohort study.
AB  - BACKGROUND: Induced abortion has been inconsistently associated with breast
      cancer risk in case-control studies. Retrospective cohort studies using registry
      information in Scandinavia have not suggested an increase in the incidence of
      breast cancer, although data on individual reproductive factors were not
      accounted for. METHODS: We examined the association between induced and
      spontaneous abortion and the incidence of breast cancer in a prospective cohort
      of young women, the Nurses' Health Study II. The study included 105 716 women 29
      to 46 years old at the start of follow-up in 1993. Information on induced or
      spontaneous abortions was collected in 1993 and updated biennially. During 973
      437 person-years of follow-up between 1993 and 2003, 1458 newly diagnosed cases
      of invasive breast cancer were ascertained. RESULTS: A total of 16 118
      participants (15%) reported a history of induced abortion, and 21 753 (21%)
      reported a history of spontaneous abortions. The hazard ratio for breast cancer
      among women who had 1 or more induced abortions was 1.01 (95% confidence
      interval, 0.88-1.17) after adjustment for established breast cancer risk factors;
      among women with 1 or more spontaneous abortions, the covariate-adjusted hazard
      ratio was 0.89 (95% confidence interval, 0.78-1.01). The relation between induced
      abortion and the incidence of breast cancer did not differ materially by number
      of abortions (P for trend = .98), age at abortion (P for trend = .68), parity (P
      for interaction = .54), or timing of abortion with respect to a full-term
      pregnancy (P for interaction = .10). CONCLUSION: Among this predominantly
      premenopausal population, neither induced nor spontaneous abortion was associated
      with the incidence of breast cancer.

PMID- 17452546
TI  - Inverse associations of Helicobacter pylori with asthma and allergy.
AB  - BACKGROUND: Acquisition of Helicobacter pylori, which predominantly occurs before
      age 10 years, may reduce risks of asthma and allergy. METHODS: We evaluated the
      associations of H pylori status with history of asthma and allergy and with skin
      sensitization using data from 7663 adults in the Third National Health and
      Nutrition Examination Survey. Adjusted odds ratios (ORs) for currently and ever
      having asthma, allergic rhinitis, allergy symptoms in the previous year, and
      allergen-specific skin sensitization were computed comparing participants
      seropositive for cagA(-) or cagA(+) strains of H pylori with those without H
      pylori. RESULTS: The presence of cagA(+) H pylori strains was inversely related
      to ever having asthma (OR, 0.79; 95% confidence interval [CI], 0.63-0.99), and
      the inverse association of cagA positivity with childhood-onset (age </=15 years)
      asthma was stronger (OR, 0.63; 95% CI, 0.43-0.93) than that with adult-onset
      asthma (OR, 0.97; 95% CI, 0.72-1.32). Colonization with H pylori, especially with
      a cagA(+) strain, was inversely associated with currently (OR, 0.77; 95% CI, 0.62
      0.96) or ever (OR, 0.77; 95% CI, 0.62-0.94) having a diagnosis of allergic
      rhinitis, especially for childhood onset (OR, 0.55; 95% CI, 0.37-0.82).
      Consistent inverse associations were found between H pylori colonization and the
      presence of allergy symptoms in the previous year and sensitization to pollens
      and molds. CONCLUSION: These observations support the hypothesis that childhood
      acquisition of H pylori is associated with reduced risks of asthma and allergy.

PMID- 17452547
TI  - Using video images of dementia in advance care planning.
AB  - BACKGROUND: Advance care planning is a process by which patients plan for future
      medical care under circumstances of impaired decision-making. Central to this
      process is the patient's understanding and ability to imagine future health
      states. METHODS: A before and after oral survey was used to compare the effect of
      a video depiction with that of a verbal description of a patient with advanced
      dementia for individuals selecting level of medical care at 7 primary care
      clinics at 2 US medical centers. The study enrolled 120 adults, half of whom were
      nonwhite. RESULTS: A total of 120 subjects completed the interview. Before
      watching the video, 60 (50.0%) subjects preferred comfort care, 25 (20.8%)
      desired life-prolonging care, 22 (18.3%) chose limited care, and 13 (10.8%) were
      unsure of their preferences. Subject preferences changed significantly after the
      video: 107 (89.2%) of the subjects chose comfort care, none desired life
      prolonging care, 10 (8.3%) chose limited care, and 3 (2.5%) were unsure of their
      preferences (P < .001). Unadjusted analysis revealed a statistically significant
      difference regarding preferences, based on race/ethnicity, before watching the
      video: 40% of African Americans and 43% of Latinos chose comfort care, compared
      with 58% of whites (P = .04). Differences were also noted for educational level
      (P = .03). After the video, differences in preferences based on race/ethnicity
      and educational level disappeared. CONCLUSIONS: Watching the video significantly
      changed preferences for care, transcending apparent differences in preferences
      associated with race/ethnicity and educational level. This study suggests that
      using video in addition to improved verbal communication may lead to more
      informed advance care planning by enhancing the ability of patients to imagine a
      hypothetical health state.

PMID- 17452548
TI  - Age- and sex-associated trends in bloodstream infection: a population-based study
      in Olmsted County, Minnesota.
AB  - BACKGROUND: Despite increasing concerns about antimicrobial resistance and
      emerging pathogens among blood culture isolates, contemporary population-based
      data on the age- and sex-specific incidence of bloodstream infections (BSIs) are
      limited. METHODS: Retrospective, population-based, cohort study of all residents
      of Olmsted County, Minnesota, with a BSI between January 1, 2003, and December
      31, 2005. The medical record linkage system of the Rochester Epidemiology Project
      and microbiology records were used to identify incident cases. RESULTS: A total
      of 1051 unique patients with positive blood culture results were identified; 401
      (38.2%) were classified as contaminated. Of 650 patients with cultures deemed
      clinically relevant, the mean +/- SD age was 63.1 +/- 23.1 years, and 52.5% were
      male. The most common organisms identified were Escherichia coli (in 163 patients
      with BSIs [25.1%]) and Staphylococcus aureus (in 108 patients with BSIs [16.6%]).
      Nosocomial BSIs were more common in males than females (23.8% vs 13.9%; P =
      .002). The age-adjusted incidence rate of BSI was 156 per 100 000 person-years
      for females and 237 per 100 000 person-years for males (P<.001), with an age- and
      sex-adjusted rate of 189 per 100 000 person-years. Rates of BSI due to gram
      positive cocci were 64 per 100 000 person-years for females and 133 per 100 000
      person-years for males (P<.001); gram-negative bacillus BSI rates (85/100 000
      person-years for females and 79/100 000 person-years for males) were not
      significantly different between sexes (P = .79). The rate of S aureus BSI was 23
      per 100 000 person-years for females and 46 per 100 000 person-years for males (P
      = .005). CONCLUSIONS: There are significant differences in the age and sex
      distribution of organisms among patients with BSIs. The incidence of BSI
      increases sharply with increasing age and is significantly higher in males,
      mainly because of nosocomial organisms, including S aureus.

PMID- 17452549
TI  - Nononcologic use of human recombinant erythropoietin therapy in hospitalized
      patients.
AB  - BACKGROUND: Human recombinant erythropoietin (rHuEPO) is widely used to stimulate
      red blood cell production in patients with anemia due to cancer, renal disease,
      and other medical conditions, but concern has grown about its overuse and
      potential for harm. Little is known about the nature of rHuEPO use in
      hospitalized patients who receive rHuEPO therapy for nononcologic indications.
      METHODS: We reviewed the drug utilization data from a large academic medical
      center for all patients admitted during 3 years to identify all patients without
      cancer who received at least 1 dose of rHuEPO, including their age and sex;
      diagnoses; hematocrit and hemoglobin and iron levels; and use of supplemental
      iron. We also compared the rates of laboratory testing and iron supplementation
      in patients with and without chronic kidney disease (CKD). RESULTS: A total of
      1360 distinct patients with 3094 hospitalizations received at least 1 dose of
      rHuEPO. In 2959 admissions for which hematocrit was determined within 14 days
      before rHuEPO use, mean values were less than 33% in 1792 (61%) and greater than
      36% in 553 (19%). Patients with CKD were more likely than patients without CKD to
      receive rHuEPO with hematocrit greater than 36% (22% vs 8%; P<.001). Monitoring
      of iron status was more common in patients with CKD than in those without CKD
      (64% vs 45%; P <.001). Almost one fourth (23%) of rHuEPO recipients in whom iron
      levels were measured had absolute iron deficiency (serum ferritin concentration
      <100 ng/mL). In patients with CKD, only about half (54%) had adequate iron stores
      at the time of rHuEPO administration; this rate was even lower in patients
      without CKD (33%; P<.001). Only 66% of patients with documented iron deficiency
      who were receiving rHuEPO also received concomitant iron supplementation; this
      rate did not differ between patients with or without CKD. CONCLUSIONS: There is
      significant variability in the degree of anemia, completeness of iron
      measurement, and use of iron supplementation in hospitalized patients without
      cancer who are prescribed rHuEPO. Our results identify potential targets for
      quality improvement in patients both with and without CKD.

PMID- 17452550
TI  - Physician follow-up and provider continuity are associated with long-term
      medication adherence: a study of the dynamics of statin use.
AB  - BACKGROUND: Many patients who initiate statin (3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitor) therapy discontinue treatment within 1 year. We
      sought to estimate the rate at which patients reinitiate treatment after long
      periods of nonadherence and to determine whether reinitiation of treatment is
      linked to potentially modifiable factors such as physician visits, cholesterol
      testing, or other encounters with the health care system. METHODS: We studied new
      users of statins in British Columbia, Canada, who initiated treatment between
      January 1, 1997, and June 30, 2004, and who had an extended period of
      nonadherence, defined as at least 90 days after the completion of 1 prescription
      in which no refill for any statin medication was obtained. Survival analysis was
      used to estimate the rate of reinitiation of statin therapy. Case-crossover
      analysis was used to evaluate the predictors of reinitiation. RESULTS: We
      identified 239 911 new users of statins, of whom 129 167 (53.8%) had a period of
      nonadherence that lasted for at least 90 days. Of these patients, an estimated
      48% restarted treatment within 1 year and 60% restarted treatment within 2 years.
      Case-crossover analysis revealed events that were associated with a return to
      adherence, including visits with the physician who initiated the statin regimen
      (odds ratio [OR], 6.1; 95% confidence interval [CI], 5.9-6.3), a visit with
      another physician (OR, 2.9; 95% CI, 2.8-3.0), and a cholesterol test (OR, 1.5;
      95% CI, 1.4-1.5). Incident myocardial infarction (OR, 12.2; 95% CI, 8.9-16.9) and
      other cardiovascular disease-related hospitalizations (OR, 3.6; 95% CI, 3.1-4.3)
      were also strong predictors of reinitiation of treatment. CONCLUSIONS: Physicians
      should be aware that statin use is dynamic and that many patients have long
      periods of nonadherence. A follow-up visit with the physician who wrote the
      initial statin prescription and having a cholesterol test predicted reinitiation
      of statin therapy. Our results suggest that continuity of care combined with
      increased follow-up and cholesterol testing could promote long-term adherence by
      shortening or eliminating long gaps in statin use. This hypothesis should be
      confirmed in a randomized experiment.

PMID- 17452551
TI  - Passive transfer of peanut hypersensitivity by fresh frozen plasma.

PMID- 17452552
TI  - Community-associated methicillin-resistant Staphylococcus aureus skin and soft
      tissue infections in men who have sex with men in New York City.

PMID- 17452553
TI  - Exogenous insulin use and hypertension.

PMID- 17452554
TI  - It is time we ended the myth of insulin as an atherogenic hormone.

PMID- 17452555
TI  - Medication adherence and physician communication skills.

PMID- 17452556
TI  - The National Student Research Group of the AADR--an introduction.
AB  - The 2005-06 officers of the National Student Research Group (NSRG) of the
      American Association for Dental Research (AADR) have summarized their activities
      in developing the NSRG into an effective organization aimed at fostering future
      dental researchers. The officers have focused their efforts on establishing
      opportunities for the pre-doctoral dental student members of the AADR to
      participate in and formally present their research during dental school. In
      addition to the many research awards and fellowships already sponsored by the
      NSRG and the AADR, the NSRG has established new travel awards for students to
      present at specialty groups' annual meetings. Other recent initiatives have
      included a contact list of all dental schools, along with local student research
      group (SRG) leadership contacts, advice during the creation of a new teaching
      fellowship opportunity, fundraising efforts to support student research and the
      NSRG infrastructure, and successfully pursuing a student voting position on the
      AADR Board. A brief addendum detailing recent activities and future initiatives
      is also included. The article describes membership requirements, selection of
      officers, and contacts for additional information. We hope that this Discovery!
      will serve to increase the awareness of students, researchers, and administrators
      regarding the role of the NSRG.

PMID- 17452557
TI  - Hereditary dentin defects.
AB  - By the Shields classification, articulated over 30 years ago, inherited dentin
      defects are divided into 5 types: 3 types of dentinogenesis imperfecta (DGI), and
      2 types of dentin dysplasia (DD). DGI type I is osteogenesis imperfecta (OI) with
      DGI. OI with DGI is caused, in most cases, by mutations in the 2 genes encoding
      type I collagen. Many genes are required to generate the enzymes that catalyze
      collagen's diverse post-translational modifications and its assembly into fibers,
      fibrils, bundles, and networks. Rare inherited diseases of bone are caused by
      defects in these genes, and some are occasionally found to include DGI as a
      feature. Appreciation of the complicated genetic etiology of DGI associated with
      bony defects splintered the DGI type I description into a multitude of more
      precisely defined entities, all with their own designations. In contrast, DD-II,
      DGI-II, and DGI-III, each with its own pattern of inherited defects limited to
      the dentition, have been found to be caused by various defects in DSPP (dentin
      sialophosphoprotein), a gene encoding the major non-collagenous proteins of
      dentin. Only DD-I, an exceedingly rare condition featuring short, blunt roots
      with obliterated pulp chambers, remains untouched by the revolution in genetics,
      and its etiology is still a mystery. A major surprise in the characterization of
      genes underlying inherited dentin defects is the apparent lack of roles played by
      the genes encoding the less-abundant non-collagenous proteins in dentin, such as
      dentin matrix protein 1 (DMP1), integrin-binding sialoprotein (IBSP), matrix
      extracellular phosphoglycoprotein (MEPE), and secreted phosphoprotein-1, or
      osteopontin (SPP1, OPN). This review discusses the development of the dentin
      extracellular matrix in the context of its evolution, and discusses the
      phenotypes and clinical classifications of isolated hereditary defects of tooth
      dentin in the context of recent genetic data respecting their genetic etiologies.

PMID- 17452558
TI  - Obesity, inflammation, and periodontal disease.
AB  - The prevalence of obesity has increased substantially over the past decades in
      most industrialized countries. Obesity is a systemic disease that predisposes to
      a variety of co-morbidities and complications that affect overall health. Cross
      sectional studies suggest that obesity is also associated with oral diseases,
      particularly periodontal disease, and prospective studies suggest that
      periodontitis may be related to cardiovascular disease. The possible causal
      relationship between obesity and periodontitis and potential underlying
      biological mechanisms remain to be established; however, the adipose tissue
      actively secretes a variety of cytokines and hormones that are involved in
      inflammatory processes, pointing toward similar pathways involved in the
      pathophysiology of obesity, periodontitis, and related inflammatory diseases. We
      provide an overview of the definition and assessment of obesity and of related
      chronic diseases and complications that may be important in the periodontist's
      office. Studies that have examined the association between obesity and
      periodontitis are reviewed, and adipose-tissue-derived hormones and cytokines
      that are involved in inflammatory processes and their relationship to
      periodontitis are discussed. Our aim is to raise the periodontist's awareness
      when treating obese individuals.

PMID- 17452559
TI  - Effectiveness of fluoride in preventing caries in adults.
AB  - To date, no systematic reviews have found fluoride to be effective in preventing
      dental caries in adults. The objective of this meta-analysis was to examine the
      effectiveness of self- and professionally applied fluoride and water fluoridation
      among adults. We used a random-effects model to estimate the effect size of
      fluoride (absolute difference in annual caries increment or relative risk ratio)
      for all adults aged 20+ years and for adults aged 40+ years. Twenty studies were
      included in the final body of evidence. Among studies published after/during
      1980, any fluoride (self- and professionally applied or water fluoridation)
      annually averted 0.29 (95%CI: 0.16-0.42) carious coronal and 0.22 (95%CI: 0.08
      0.37) carious root surfaces. The prevented fraction for water fluoridation was
      27% (95%CI: 19%-34%). These findings suggest that fluoride prevents caries among
      adults of all ages.

PMID- 17452560
TI  - Gene polymorphisms and the prevalence of key periodontal pathogens.
AB  - Growing evidence suggests that individual genetic susceptibility may influence
      the host's response to infections. The aim of this project was to study whether
      gene polymorphisms of inflammatory markers are associated with the presence of
      viable periodontopathogenic bacteria. We extracted genomic DNA from 45 young
      adults diagnosed with generalized aggressive periodontitis to study Fc receptors,
      formyl peptide receptor, Interleukin-6, tumor necrosis factor-alpha, and vitamin
      D receptor polymorphisms. The presence and viable numbers of Actinobacillus
      actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythensis were
      determined by culture, and their identities confirmed by PCR. Multiple logistic
      regressions revealed that both Fcgamma receptor and IL-6 -174 polymorphisms were
      associated with increased odds of detecting A. actinomycetemcomitans, P.
      gingivalis, and T. forsythensis after adjustment for age, ethnicity, smoking, and
      periodontitis extent. These findings support the hypothesis that complex
      interactions between the microbiota and host genome may be at the basis of
      susceptibility to aggressive periodontitis.

PMID- 17452561
TI  - Sequence of oral bacterial co-adhesion and non-contact brushing.
AB  - Non-contact plaque removal offers advantages in interproximal spaces, fissures,
      and pockets. It requires the generation of strong fluid flows and the inclusion
      of air bubbles to become effective. A pair of co-adhering streptococci and
      actinomyces has been used previously to demonstrate non-contact removal by sonic
      brushing. Here we determined the influence of the sequence of co-adhesion of
      streptococci and actinomyces on non-contact removal from a salivary pellicle by
      rotary and sonic brushing. After bacterial adhesion, pellicles were brushed in a
      wet and immersed state, with a distance up to 4 mm to the bristle tips. Bacteria
      adhering to pellicles from the sequence streptococci followed by actinomyces
      appeared more difficult to remove and left more large co-aggregates than from the
      sequence actinomyces followed by streptococci. At contact, rotary and sonic
      brushing performed equally well in bacterial removal, while at 4 mm, both had
      lost some efficacy.

PMID- 17452562
TI  - Self-assembling peptide scaffolds promote enamel remineralization.
AB  - Rationally designed beta-sheet-forming peptides that spontaneously form three
      dimensional fibrillar scaffolds in response to specific environmental triggers
      may potentially be used in skeletal tissue engineering, including the
      treatment/prevention of dental caries, via bioactive surface groups. We
      hypothesized that infiltration of caries lesions with monomeric low-viscosity
      peptide solutions would be followed by in situ polymerization triggered by
      conditions of pH and ionic strength, providing a biomimetic scaffold capable of
      hydroxyapatite nucleation, promoting repair. Our aim was to determine the effect
      of an anionic peptide applied to caries-like lesions in human dental enamel under
      simulated intra-oral conditions of pH cycling. Peptide treatment significantly
      increased net mineral gain by the lesions, due to both increased remineralization
      and inhibition of demineralization over a five-day period. The assembled peptide
      was also capable of inducing hydroxyapatite nucleation de novo. The results
      suggest that self-assembling peptides may be useful in the modulation of mineral
      behavior during in situ dental tissue engineering.

PMID- 17452563
TI  - Protection offered by root-surface restorative materials against biofilm
      challenge.
AB  - The prevalence of root-surface caries is increasing. We hypothesized that some
      restorative materials are protective against cariogenic challenge on root
      surfaces. Our goal was to study the effects of different restorative materials on
      root surfaces incubated with an oral biofilm generated in an artificial mouth. A
      biofilm of Streptococcus mutans, Streptococcus sobrinus, Lactobacillus rhamnosus,
      and Actinomyces naeslundii was co-cultured for 21 days on 24 glass-ionomer
      cement, resin-modified glass-ionomer cement, or resin-composite-restored root
      surfaces. These surfaces were then examined with Fourier transform infrared
      spectroscopy and scanning electron energy-dispersive spectroscopy. Only glass
      ionomer restorations showed a significant increase in log calcium-to-phosphorus
      ratio (P < 0.01), and a significantly lower log amide I-to-hydrogen phosphate
      ratio on the root surface after incubation in the artificial mouth. Glass-ionomer
      restoratives conferred a preventive effect on the root surfaces against initial
      cariogenic challenge with a mixed-species oral biofilm without therapeutic
      intervention.

PMID- 17452564
TI  - Zymographic analysis and characterization of MMP-2 and -9 forms in human sound
      dentin.
AB  - The role and function of dentin matrix metalloproteinases (MMPs) are not well
      understood, but they may play a key role in dentinal caries and the degradation
      of resin-bonded dentin matrices. To test the null hypothesis that MMP-9 is not
      found in dentin matrix, we used gelatin zymography to extract and isolate all
      molecular forms of gelatinolytic MMPs in demineralized mature sound dentin powder
      obtained from extracted human molars, characterizing and identifying the enzymes
      by Western blotting. Gelatinolytic MMPs were detected in extracts of
      demineralized dentin matrix and identified as MMP-2 and MMP-9. Acidic extracts
      (pH 2.3) yielded 3-8 times more MMP activity than did EDTA (pH 7.4). Their
      activation may contribute to dentin matrix degradation, which occurs during
      caries progression and following resin bonding. Inhibition of MMP-2 and -9
      proteolytic activity may slow caries progression and increase the durability of
      resin-dentin bonds.

PMID- 17452565
TI  - In vitro evaluation of corrosion and cytotoxicity of orthodontic brackets.
AB  - The corrosion resistance of AISI 304 stainless steel (AISI 304 SS) and manganese
      stainless steel (low-nickel SS) brackets in artificial saliva was investigated.
      The cytotoxic effects of their corrosion products on L929 cell culture were
      compared by two assays, crystal violet, to evaluate cell viability, and MTT (3
      [4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide), for cell metabolism
      and proliferation. The atomic absorption spectroscopic analysis of the corrosion
      products demonstrated that nickel and manganese ion concentrations were higher
      for the AISI 304 SS-bracket immersion solution as compared with the low-nickel SS
      brackets. Scanning electron microscopy and energy-dispersive spectroscopy
      demonstrated less corrosion resistance for the AISI 304 SS brackets. Although
      none of the bracket extracts altered L929 cell viability or morphology, the AISI
      304 SS-bracket extracts decreased cellular metabolism slightly. The results
      indicated that the low-nickel SS presents better in vitro biocompatibility than
      AISI 304 SS brackets. Abbreviations used: AISI, American Iron and Steel
      Institute; EDS, energy-dispersive spectroscopy; OD, optical density; ISO,
      International Organization for Standardization; MTT, (3-{4,5 dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide; NiSO(4), nickel sulfate; SEM, standard error
      of the mean; WHO, World Health Organization; and TNF, tumor necrosis factor.

PMID- 17452566
TI  - Arg-gingipain A DNA vaccine prevents alveolar bone loss in mice.
AB  - One major pathogenic factor of Porphyromonas gingivalis is Arg-gingipain (Rgp),
      an arginine-specific cysteine proteinase. To clarify the effect of rgpA DNA
      vaccine, we immunized BALB/c mice via the abdomen with a Gene Gun or via the
      nasal cavity weekly for 6 weeks. After immunization, the mice were challenged
      orally with P. gingivalis. Immunization elicited IgG responses against P.
      gingivalis in both groups. Nasal immunization also induced sIgA against P.
      gingivalis, although Gene Gun immunization did not. Reduction of alveolar bone
      loss was observed in both groups at 42 days following initial infection. This
      effect was more pronounced in the intranasal immunization group than in the Gene
      Gun group. The results of this study suggest that immunization with rgpA DNA
      vaccine via the nasal cavity is an effective method for preventing alveolar bone
      loss incurred by infection with P. gingivalis.

PMID- 17452567
TI  - Effect of aqueous ozone on the NF-kappaB system.
AB  - Ozone has been proposed as an alternative oral antiseptic in dentistry, due to
      its antimicrobial power reported for gaseous and aqueous forms, the latter
      showing a high biocompatibility with mammalian cells. New therapeutic strategies
      for the treatment of periodontal disease and apical periodontitis should consider
      not only antibacterial effects, but also their influence on the host immune
      response. Therefore, our aim was to investigate the effect of aqueous ozone on
      the NF-kappaB system, a paradigm for inflammation-associated
      signaling/transcription. We showed that NF-kappaB activity in oral cells
      stimulated with TNF, and in periodontal ligament tissue from root surfaces of
      periodontally damaged teeth, was inhibited following incubation with ozonized
      medium. Under this treatment, IkappaBalpha proteolysis, cytokine expression, and
      kappaB-dependent transcription were prevented. Specific ozonized amino acids were
      shown to represent major inhibitory components of ozonized medium. In summary,
      our study establishes a condition under which aqueous ozone exerts inhibitory
      effects on the NF-kappaB system, suggesting that it has an anti-inflammatory
      capacity.

PMID- 17452568
TI  - Matrix metalloproteinase-3 differences in oral and skin fibroblasts.
AB  - While skin wounds heal by scarring, wounds of oral mucosa show privileged healing
      with minimal scar formation. Our hypothesis was that phenotypic differences
      between oral and skin fibroblasts underlie these differences in healing. The aims
      of this study were to compare MMP-3 expression by oral and skin fibroblasts and
      investigate a role for MMP-3 in mediating collagen gel contraction. Oral
      fibroblasts induced significantly greater gel contraction than did paired skin
      cells. Inhibition of MMP activity significantly inhibited gel contraction by both
      cell types. Specific inhibition of MMP-3 activity reduced gel contraction by
      oral, but not skin, fibroblasts. Oral fibroblasts produced significantly higher
      levels of MMP-3 than did skin fibroblasts at all levels studied. TGF-beta1 and 
      beta3 isoforms stimulated MMP-3 expression at mRNA, protein, and activity levels
      by both fibroblast populations. Results suggest that increased MMP-3 production
      by oral fibroblasts may underlie the differences in wound-healing outcome seen in
      skin and oral mucosa.

PMID- 17452569
TI  - Mouse molar dentin size/shape is dependent on growth hormone status.
AB  - Growth hormone (GH) status affects dental development, but how GH influences
      tooth size/shape is unclear. Since GH affects dental epithelial proliferation, we
      hypothesized that GH influences the tooth crown and root dimensions. Dentin
      matrix dimensions were measured in longitudinal sections of decalcified first
      mandibular molars from 3 genetically modified mice: giant (GH-Excess) mice and
      dwarf (GH-Antagonist and GH-Receptor-Knockout) mice. GH status was found to
      influence crown width, root length, and dentin thickness. Analysis of these data
      suggests that GH influences both tooth crown and root development prior to
      dentinogenesis as well as during appositional growth of dentin. This is
      concordant with the expression of paracrine GH and GH receptors during tooth bud
      morphogenesis, and of GH receptors in the enamel organ, dental papilla, and
      Hertwig's epithelial root sheath during dentinogenesis. Based on prior studies,
      these GH morphogenetic actions may be mediated by the induction of both bone
      morphogenetic protein and insulin-like growth factor-1 expression.

PMID- 17452570
TI  - Hard tissue formation in subcutaneously transplanted rat dental pulp.
AB  - While dental pulp appears to be able to form mineralized matrices that do not
      always resemble dentin, the precise characteristics of the hard tissue and the
      mechanism of its induction remain unknown. Therefore, we evaluated hard tissue
      induced by transplantation of pulp into subcutaneous tissue. Seven days after
      transplantation, initial hard tissue was formed at the inner periphery of the
      pulp. After 14 days, this hard tissue expanded inwardly. Mineralized matrix was
      immunopositive for osteocalcin, osteopontin, and bone sialoprotein, but negative
      for dentin sialoprotein. Transplantation of GFP-labeled pulp into wild-type rats
      showed these formative cells to have been derived from the transplant. TEM
      observation revealed apatite crystals within necrotic cells and matrix vesicles
      at the initial stage of calcification. These results indicate that pulp cells
      possess the ability to form a bone- or cementum-like matrix. Calcification of the
      matrix may occur in necrotic cells and matrix vesicles, followed by collagenous
      calcification.

PMID- 17452571
TI  - Effects of COX-2 inhibitor in temporomandibular joint acute inflammation.
AB  - Since it is recognized that cyclo-oxygenase-2 mediates nociception and the sleep
      wake cycle as well, and that acute inflammation of the temporomandibular joint
      (TMJ) results in sleep disturbances, we hypothesized that cyclo-oxygenase-2
      inhibitor would restore the sleep pattern in this inflammatory rat model. First,
      sleep was monitored after the injection of Freund's adjuvant (FA group) or saline
      (SHAM group) into the rats' temporomandibular joint. Second, etoricoxib was co
      administered in these groups. The Freund's adjuvant group showed a reduction in
      sleep efficiency, in rapid eye movement (REM), and in non-REM sleep, and an
      increase in sleep and REM sleep latency when compared with the SHAM group, while
      etoricoxib substantially increased sleep quality in the Freund's adjuvant group.
      These parameters returned progressively to those found in the SHAM group.
      Etoricoxib improved the sleep parameters, suggesting the involvement of the cyclo
      oxygenase-2 enzyme in acute inflammation of the TMJ, specifically in REM sleep.

PMID- 17452572
TI  - How migraines affect cognitive function.

PMID- 17452575
TI  - Head-shaking nystagmus and new technology.

PMID- 17452576
TI  - Better late than never?: the story of arterial recanalization in acute ischemic
      stroke.

PMID- 17452577
TI  - Head-shaking nystagmus in lateral medullary infarction: patterns and possible
      mechanisms.
AB  - OBJECTIVE: Horizontal head shaking at 2 to 3 Hz can induce nystagmus in patients
      with central as well as in patients with peripheral vestibulopathy. However, the
      characteristics and diagnostic value of this post-head-shaking nystagmus (HSN)
      have not been studied systematically in central vestibulopathy, and little is
      known of the mechanisms involved. METHODS: We analyzed spontaneous and HSN and
      the effects of baclofen, a GABA(B) agonist, in 16 patients with acute lateral
      medullary infarction. RESULTS: These patients showed several characteristics of
      HSN unlike those observed in peripheral vestibulopathy. HSN was observed in 14 of
      16 patients (87.5%), and in all cases, the horizontal component beats toward the
      lesion side, i.e., was ipsilesional. Even in the eight patients with
      contralesional spontaneous horizontal nystagmus, the HSN was opposite to the
      spontaneous nystagmus. Three patients showed unusually strong HSN with a maximum
      slow-phase velocity greater than 60 degrees/second. Visual fixation markedly
      suppressed HSN and baclofen reduced HSN. In most of the patients, MRI showed
      infarctions in the caudal or middle portion of the medulla and spared the rostral
      portion. CONCLUSIONS: We propose that head-shaking nystagmus in lateral medullary
      infarction is due to unilaterally impaired nodulouvular inhibition of the
      velocity storage. This proposal is consistent with the results of neuroanatomic
      studies that demonstrate that Purkinje cells controlling velocity storage in the
      nodulus and ventral uvula project to the caudal or middle portion of the
      vestibular nuclei, whereas those subserving visual-vestibular interactions in the
      flocculus project to the more rostral portion.

PMID- 17452578
TI  - Is DBS-STN appropriate to treat severe Parkinson disease in an elderly
      population?
AB  - OBJECTIVE: To assess the role of age in the results of bilateral deep brain
      stimulation in the subthalamic nucleus (DBS-STN), we carried out a study of two
      groups of patients regarding age at time of surgery. METHODS: We compared, up to
      2 years after surgery, the clinical effects, safety, and quality of life in
      parkinsonian patients younger than 65 years old (young patients) vs parkinsonian
      patients 65 years old or older (old patients). RESULTS: The mean age was 57.4 +/-
      4.9 years (n = 53) in young patients and 68.8 +/- 2.8 years (n = 34) in old
      patients. A dramatic improvement in motor complications was equally observed in
      both groups of patients. There was no significant difference between the groups
      regarding acute effects of DBS-STN on the motor score of the Unified Parkinson's
      Disease Rating Scale part III (UPDRS III). Time course evolution of UPDRS the
      motor score (p < 0.0001) and axial score (p = 0.0001) assessed postoperatively in
      "on" medication and "on" stimulation conditions appeared worse in old patients as
      compared to young patients. Improvement in the Schwab and England Scale score was
      better in young patients in "on" (p < 0.0003) and "off" state (p < 0.001).
      Quality of life assessed with the 39-item Parkinson's Disease Questionnaire
      showed an improvement in subscales evaluating mobility (p < 0.0001), activities
      of daily life (p < 0.0001), emotion and stigma (p = 0.0004), cognition (p <
      0.0074), and communication (p = 0.0029) in young patients as compared to old
      patients. Side effects were similar in the two groups. CONCLUSIONS: Although deep
      brain stimulation in the subthalamic nucleus reduces motor complications equally
      in both groups of patients, postoperative quality of life improved only in young
      patients.

PMID- 17452579
TI  - Quetiapine for agitation or psychosis in patients with dementia and parkinsonism.
AB  - OBJECTIVE: To assess the efficacy and tolerability of quetiapine for agitation or
      psychosis in patients with dementia and parkinsonism. METHODS: Multicenter
      randomized, double-blind, placebo-controlled parallel groups clinical trial
      involving 40 patients with dementia with Lewy bodies (n = 23), Parkinson disease
      (PD) with dementia (n = 9), or Alzheimer disease with parkinsonian features (n =
      8). The main outcome measure for efficacy was change in the Brief Psychiatric
      Rating Scale (BPRS) from baseline to 10 weeks of therapy. For tolerability it was
      change in the Unified PD Rating Scale (UPDRS) motor section over the same time
      period. The trial was confounded by the need for a design change and incomplete
      recruitment. RESULTS: No significant differences in the primary or secondary
      outcome measures of efficacy were observed. An unexpectedly large placebo effect,
      inadequate dosage (mean 120 mg/day), and inadequate power may have contributed to
      lack of demonstrable benefit. Quetiapine was generally well-tolerated and did not
      worsen parkinsonism, but was associated with a trend toward a decline on a
      measure of daily functioning. CONCLUSIONS: Quetiapine was well-tolerated and did
      not worsen parkinsonism. Although conclusions about efficacy may be limited, the
      drug in the dosages used did not show demonstrable benefit for treating agitation
      or psychosis in patients with dementia and parkinsonism. These findings are in
      keeping with prior studies reporting limited efficacy of various medications for
      reducing behavioral problems in demented patients.

PMID- 17452580
TI  - Recanalization after intravenous thrombolysis: does a recanalization time window
      exist?
AB  - BACKGROUND: To evaluate the time course of major vessel recanalization under IV
      thrombolysis in relation to functional outcome in acute ischemic stroke. METHODS:
      A total of 99 patients with an acute anterior circulation vessel occlusion who
      underwent IV thrombolysis were included. All patients had a standardized
      admission and follow-up procedure. Color-coded duplex sonography was performed on
      admission, 30 minutes after thrombolysis, and at 6 and 24 hours after onset of
      symptoms. Recanalization was classified as complete, partial, and absent.
      Functional outcome was rated with the modified Rankin Scale on day 30. RESULTS:
      Complete recanalization occurred significantly more frequently in patients with
      multiple branch occlusions compared to those with mainstem occlusion (OR 5.33;
      95% CI, 2.18 to 13.05; p < 0.0001) and was associated with lower NIH Stroke Scale
      (NIHSS) scores (p < 0.001). Not the specific time point of recanalization at 6 or
      24 hours after stroke onset, but recanalization per se within 24 hours (OR 7.8;
      95% CI 2.2 to 28.2; p = 0.002) was significantly associated with a favorable
      outcome. Multivariate analysis revealed recanalization at any time within 24
      hours and NIHSS scores on days 1 and 7 together explaining 75% of the functional
      outcome variance 30 days after stroke. CONCLUSIONS: Complete recanalization up to
      24 hours after stroke onset is significantly associated with the short-term
      clinical course and functional outcome 30 days after acute stroke.

PMID- 17452581
TI  - Hepatic disease as the first manifestation of progressive myoclonus epilepsy of
      Lafora.
AB  - BACKGROUND: Lafora disease (LD; progressive myoclonus epilepsy type 2; EPM2) is
      an autosomal recessive disorder caused by mutations in the EPM2A and EPM2B genes.
      LD is characterized by the presence of strongly PAS-positive intracellular
      inclusions (Lafora bodies) in several tissues. Glycogen storage disease type IV
      (GSD-IV; Andersen disease) is an autosomal recessive disorder characterized by
      cirrhosis leading to severe liver failure. GSD-IV has been associated with
      mutations in the glycogen branching enzyme gene (GBE). Histopathologic changes of
      the liver in both diseases show an identical appearance, although cirrhosis has
      never been described in patients with LD. We report a LD family in which the
      proband presented severe liver failure at onset of the disease. METHODS: Clinical
      histories, physical and neurologic examination, laboratory tests, EEGs, MRI of
      the brain, and liver or axillary skin biopsies were performed in the two affected
      siblings. The diagnosis was confirmed by molecular genetic analysis of the EPM2A,
      EPM2B, and GBE genes and loci. RESULTS: During the first decade of life,
      abnormalities in liver function tests were detected in the two affected siblings.
      The proband's liver dysfunction was severe enough to require liver
      transplantation. Subsequently, both sibs developed LD. Mutation analysis of EPM2A
      revealed a homozygous Arg241stop mutation in both patients. CONCLUSIONS: This is
      the first description of severe hepatic dysfunction as the initial clinical
      manifestation of LD. The phenotypic differences between the two affected siblings
      suggest that modifier genes must condition clinical expression of the disease
      outside the CNS.

PMID- 17452582
TI  - New locus for febrile seizures with absence epilepsy on 3p and a possible
      modifier gene on 18p.
AB  - OBJECTIVE: To report a clinical and genetic study of a large family with febrile
      seizures (FS) and childhood absence epilepsy (CAE). METHODS: This family was
      identified through a French campaign for familial epilepsies. It spans four
      generations and consists of 51 members, 13 of whom were affected. The medical
      history of all members was obtained by personal information and by consulting the
      medical files of affected members. All family members gave written consent to
      participate in the study. RESULTS: All affected members presented FS, with CAE in
      five and temporal lobe epilepsy (TLE) in one. FS stopped before age 6 years in
      all but one patient. FS were simple, except in one patient who had a long-lasting
      complex FS at 8 months of age. He later presented pharmacoresistant TLE and left
      hippocampal sclerosis was visible on brain MRI. Patients presenting CAE had
      recorded absences and characteristic EEGs with 3 Hz spike waves. After exclusion
      of reported loci for FS and generalized epilepsy with FS plus, a genome-wide
      search allowed us to map a new locus for FS on 3p. We could not exclude another
      genomic segment on chromosome 18p and all patients presenting epilepsy (CAE and
      TLE) shared a common haplotype at this locus in addition to the haplotype on 3p.
      CONCLUSION: These findings emphasize the genetic heterogeneity of febrile
      seizures. Furthermore, epilepsy in association with febrile seizures might result
      in this family from an interaction between at least two genes: the gene on 3p and
      a possible modifier gene on 18p.

PMID- 17452583
TI  - FAME 3: a novel form of progressive myoclonus and epilepsy.
AB  - BACKGROUND: Familial adult myoclonic epilepsy (FAME) is associated with
      myoclonus, tremor, and rare seizures, and is a nonprogressive disorder linked to
      the FAME 1 locus. A similar disorder has been linked to the FAME 2 locus.
      METHODS: Seventeen patients from two families with myoclonus and epilepsy were
      evaluated clinically and underwent EEG, EMG, jerk-locked averaging, and MRI
      scanning. Three had responses to magnetic stimulation assessed. Linkage was
      assessed for microsatellite markers across the FAME 1 and 2 loci. RESULTS: The
      median age at onset was 20 years, with many patients having frequent seizures,
      cognitive impairment, and cerebellar dysfunction. Electrophysiologic features of
      cortical myoclonus were typically present, but photosensitivity was uncommon. MRI
      frequently demonstrated cerebellar atrophy. Pathology of a single case showed
      Purkinje cell loss, dentate atrophy, and neuronal loss and gliosis in the olives
      and pallidum. Analysis of genotypes for markers at the FAME 1 and FAME 2 loci
      excluded these as the region containing the same locus in one family, but only
      the FAME 2 locus was excluded in the other family. CONCLUSIONS: This form of
      familial adult myoclonic epilepsy does not show linkage to either of the known
      familial adult myoclonic epilepsy loci, and is characterized in some members by
      frequent seizures, cerebellar ataxia, dementia, and progression of the disease.
      This may represent a new form of progressive myoclonus and epilepsy, which we
      have termed familial adult myoclonic epilepsy type 3.

PMID- 17452584
TI  - MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS.
AB  - BACKGROUND: In a 2-year, placebo-controlled trial (the Natalizumab Safety and
      Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] study), involving 942
      patients with relapsing multiple sclerosis (MS), natalizumab significantly
      reduced the relapse rate by 68% and progression of sustained disability by 42% vs
      placebo. We report the effect of natalizumab on MRI measures from the AFFIRM
      study. METHODS: The number and volume of gadolinium (Gd)-enhancing, new or
      enlarging T2-hyperintense, and new T1-hypointense lesions and brain parenchymal
      fraction were measured from annual scans obtained at baseline, 1 year, and 2
      years. RESULTS: Compared with placebo, natalizumab produced a 92% decrease in Gd
      enhancing lesions (means 2.4 vs 0.2; p < 0.001), an 83% decrease in new or
      enlarging T2-hyperintense lesions (means 11.0 vs 1.9; p < 0.001), and a 76%
      decrease in new T1-hypointense lesions (means 4.6 vs 1.1; p < 0.001) over 2
      years. Median T2-hyperintense lesion volume increased by 8.8% in the placebo
      group and decreased by 9.4% in the natalizumab group (p < 0.001); median T1
      hypointense lesion volume decreased by 1.5% in the placebo group and decreased by
      23.5% in the natalizumab group (p < 0.001). Brain atrophy was greater in year 1
      and less in year 2 in natalizumab-treated patients. CONCLUSION: Natalizumab has a
      sustained effect in preventing the formation of new lesions in patients with
      relapsing multiple sclerosis.

PMID- 17452585
TI  - Quantitative objective markers for upper and lower motor neuron dysfunction in
      ALS.
AB  - OBJECTIVE: To investigate the value of objective biomarkers for upper (UMN) and
      lower (LMN) motor neuron involvement in ALS. METHODS: We prospectively studied 64
      patients with ALS and its subsets using clinical measures, proton MR
      spectroscopic imaging ((1)H MRSI), diffusion tensor imaging, transcranial
      magnetic stimulation, and the motor unit number estimation (MUNE) at baseline and
      every 3 months for 15 months and compared them with control subjects. RESULTS:
      (1)H MRSI measures of the primary motor cortex N-acetyl-aspartate (NAA)
      concentration were markedly reduced in ALS (p = 0.009) and all UMN syndromes
      combined (ALS, familial ALS [fALS], and primary lateral sclerosis; p = 0.03) vs
      control values. Central motor conduction time to the tibialis anterior was
      prolonged in ALS (p < 0.0005) and combined UMN syndromes (p = 0.001). MUNE was
      lower in ALS (p < 0.0005) and all LMN syndromes combined (ALS, fALS, and
      progressive muscular atrophy; p = 0.001) vs controls. All objective markers
      correlated well with the ALS Functional Rating Scale-Revised, finger and foot
      tapping, and strength testing, suggesting these markers related to disease
      activity. Regarding changes over time, MUNE changed rapidly, whereas neuroimaging
      markers changed more slowly and did not significantly differ from baseline.
      CONCLUSIONS: (1)H MR spectroscopic imaging measures of the primary motor cortex N
      acetyl-aspartate (NAA) concentration and ratio of NAA to creatine, central motor
      conduction time to the tibialis anterior, and motor unit number estimation
      significantly differed between ALS, its subsets, and control subjects, suggesting
      they have potential to provide insight into the pathobiology of these disorders.

PMID- 17452586
TI  - Course of cerebral amyloid angiopathy-related inflammation.
AB  - BACKGROUND: A subset of patients with cerebral amyloid angiopathy (CAA) present
      with cognitive symptoms, seizures, headaches, T2-hyperintense MRI lesions, and
      neuropathologic evidence of CAA-associated vascular inflammation. OBJECTIVE: To
      analyze the risk factors, diagnostic characteristics, and long-term course of
      this disorder. METHODS: We assessed 14 consecutive patients with pathologically
      diagnosed CAA-related inflammation, 12 with available neuroimaging and follow-up
      data. Patients were evaluated for MRI appearance, APOE genotype, and clinical
      course over a 46.8 +/- 29.1-month follow-up. RESULTS: Baseline MRI scans were
      characterized by asymmetric T2-hyperintense lesions extending to the subcortical
      white matter and occasionally the overlying gray matter, with signal properties
      suggesting vasogenic edema. Subjects could be divided into three groups based on
      response to immunosuppressive treatment: monophasic improvement (7/12), initial
      improvement followed by symptomatic relapse (3/12), and no evident response to
      treatment (2/12). The volume of MRI hyperintensities correlated with the severity
      of clinical symptoms. One patient experienced symptomatic intracerebral
      hemorrhage within a region of recurrent MRI hyperintensity. The APOE
      epsilon4/epsilon4 genotype was strongly associated with CAA-related inflammation,
      present in 76.9% (10/13) of subjects vs 5.1% (2/39) with symptomatic but
      noninflammatory CAA (p < 0.0001). CONCLUSION: Cerebral amyloid angiopathy-related
      inflammation represents a clinically, pathologically, radiographically, and
      genetically distinct disease subtype with implications for clinical practice and
      ongoing immunotherapeutic approaches to Alzheimer disease.

PMID- 17452588
TI  - AAN Board of Directors recommends formation of a companion association to
      establish a political action committee.

PMID- 17452587
TI  - How migraines impact cognitive function: findings from the Baltimore ECA.
AB  - OBJECTIVE: To examine the cross-sectional and longitudinal relationship between
      migraine headaches and cognitive functioning. METHODS: The data were from Waves
      III (1993 through 1996) and IV (2004 through 2005) of the Baltimore Epidemiologic
      Catchment Area Study. Migraine headaches were diagnosed according to modified
      criteria of the International Headache Society. Scores on the immediate and
      delayed recall tests and the Mini-Mental State Examination (MMSE) were compared
      for migraineurs (n = 204) vs nonmigraineurs (n = 1,244). The longitudinal
      association between migraine and cognitive changes was assessed by generalized
      estimating equations. RESULTS: Migraineurs scored lower on tests of immediate and
      delayed memory at baseline, but declined by less over time than nonmigraineurs.
      These associations were specific to migraineurs with aura, who declined by 1.26
      (p < 0.01) and 1.47 (p < 0.01) words less on the immediate and delayed recall
      tests over the 12 years of follow-up. The effects of migraine, specifically with
      aura, on the MMSE were restricted to those older than 50 years. Among those
      younger than 50 years, migraineurs with aura declined at the same rate on the
      MMSE as nonmigraineurs. However, among those older than 50 years, migraineurs
      with aura declined by 0.99 points (p < 0.01) less over the follow-up.
      CONCLUSIONS: Migraineurs, specifically those with aura, exhibited less decline on
      cognitive tests over time vs nonmigraineurs. For the Mini-Mental State
      Examination, these effects were only apparent among those who were older than 50
      years.

PMID- 17452589
TI  - Pilot trial of diltiazem in facioscapulohumeral muscular dystrophy.

PMID- 17452590
TI  - NARP mitochondriopathy: an unusual cause of progressive myoclonic epilepsy.

PMID- 17452591
TI  - Diagnostic value of ultrastructural skin biopsy studies in CADASIL.

PMID- 17452593
TI  - Impaired ipsilateral smooth pursuit and gaze-evoked nystagmus in paramedian
      pontine lesion.

PMID- 17452594
TI  - CT angiography and CT perfusion in post-CEA hyperperfusion syndrome.

PMID- 17452595
TI  - CSF tau protein: a new prognostic marker for Guillain-Barre syndrome.

PMID- 17452596
TI  - Quantification of neurometabolites in subacute sclerosing panencephalitis by 1H
      MRS.

PMID- 17452597
TI  - CSF opening pressure: reference interval and the effect of body mass index.

PMID- 17452598
TI  - Vitamins and entacapone in levodopa-induced hyperhomocysteinemia: a randomized
      controlled study.

PMID- 17452599
TI  - Treatment of childhood migraine attacks with oral zolmitriptan and ibuprofen.

PMID- 17452601
TI  - Does the 15-minute (or less) family interview influence family nursing practice?
AB  - A quasi-experimental, pretest/posttest study was conducted to explore nurses'
      perceptions of the impact of the 15-minute family interview on the pediatric
      hospital admission process. The intervention consisted of two in-depth teaching
      sessions, and hands-on coaching in the use of the 15-minute family interview.
      Each of the 6 nurses was interviewed twice using a semi-structured questionnaire:
      once before receiving the intervention and once after they had completed 6 family
      interviews. In addition, nurses kept field notes on their impressions of the
      family interviewing process. A thematic analysis of the data was conducted.
      Findings revealed that the nurses perceived the genogram, therapeutic questions,
      and commendations as having a positive impact on their ability to conduct family
      assessment and family interventions. Overall, nurses felt that the 15-minute
      family interview should be routinely incorporated into practice at the time of a
      child's admission.

PMID- 17452600
TI  - Distinguished contribution to Family Nursing Award: Dr. Shirley May Harmon Hanson
      for: Family health care nursing: theory, practice, and research (1996, 2001,
      2005).

PMID- 17452602
TI  - Mothers' and fathers' views of the interdependence of their relationships with
      their infant: a systems perspective on early family relationships.
AB  - This study examined the interrelatedness of mother-infant and father-infant
      relationships as they develop over the first 4 months postpartum as well as the
      dynamics used by the couple to balance these relationships. First-time mother
      father couples (n = 18) were interviewed separately at 1, 6, and 16 weeks
      postpartum using the Parent-Infant Relationship Interview. The data were analyzed
      using in-depth qualitative strategies. The parents' core themes of their early
      family relationships ranged from an undifferentiated unit at 1 week, to being a
      highly disorganized unit at 6 weeks, to a more integrated unit at 16 weeks. These
      results suggest that one should be thinking of early family relationships and
      parenting in terms of "messy processes" out of which new ways of being together
      are created. This disorganization plays a fundamental role in the establishment
      of early family relationships and warrants further empirical and clinical
      attention.

PMID- 17452603
TI  - Decision making at end of life among Japanese American families.
AB  - This exploratory study describes decision making at end of life among Japanese
      American families. Using qualitative methods including a one-time, semistructured
      interview, 16 Japanese American family participants described their experiences
      with the death of 22 family members. A grounded theory analysis led to the
      development of a model of a process that reflected the influence of age-cohort
      generational differences and health care providers' involvement. The model also
      included four dimensions of family understanding. The four dimensions were
      awareness of the seriousness of the family members' condition, decision making
      about life-sustaining treatment, readiness for impending death, and experience of
      the dying process. Each dimension reflected a continuum from low to high
      understanding. The results suggest that nurses and other health care providers
      can impact the level of understanding within each of the dimensions in culturally
      sensitive ways and contribute to improving the experience with end-of-life
      decision making for Japanese Americans.

PMID- 17452604
TI  - A family's beliefs about cancer, dying, and death in the end of life.
AB  - The purpose of this case study was to describe the beliefs over time of a Swedish
      family and individual family members about cancer and death and how these beliefs
      affected their daily lives. Data were collected over 10 months using interviews,
      conversations, and diary notations. The beliefs were aggregated into eight main
      beliefs and four themes: Cancer is a deadly threat/death is a liberator, death
      can be held at bay/death can be lived near, dying is done alone/dying should not
      be done alone, and life has an end/life is endless. These beliefs appear to
      oscillate between seemingly contrasting poles. Some beliefs were shared by all
      family members, whereas others were described by only one or more members of the
      family. The complexity of daily life in families experiencing life-shortening
      illness underscores the need of individualized nursing care with openness to
      difference and collaboration as guiding principles.

PMID- 17452605
TI  - Institutional placement of persons with dementia: what predicts occurrence and
      timing?
AB  - The decision to place an individual with dementia in an institutional care
      facility is often one of the most difficult judgments made in families. The
      purpose of this study was to determine the key variables that affect the
      occurrence and timing of institutional placement for families caring for an
      individual with dementia. The results of this study indicated that the most
      salient variables affecting the occurrence and timing of institutional placement
      for persons with dementia were the caregivers' depression scores and the care
      recipients' behavior change scores over time. These results indicate the need to
      screen for behavior change in the person with dementia and symptoms of depression
      in the caregivers to help families predict the need for institutional placement.

PMID- 17452607
TI  - Development of a ventilatory classification system in patients with heart
      failure.
AB  - BACKGROUND: Ventilatory efficiency, commonly assessed by the minute ventilation
      (VE)-carbon dioxide production (VCO2) slope, is a powerful prognostic marker in
      the heart failure population. The purpose of the present study is to refine the
      prognostic power of the VE/VCO2 slope by developing a ventilatory class system
      that correlates VE/VCO2 cut points to cardiac-related events. METHODS AND
      RESULTS: Four hundred forty-eight subjects diagnosed with heart failure were
      included in this analysis. The VE/VCO2 slope was determined via cardiopulmonary
      exercise testing. Subjects were tracked for major cardiac events (mortality,
      transplantation, or left ventricular assist device implantation) for 2 years
      after cardiopulmonary exercise testing. There were 81 cardiac-related events (64
      deaths, 10 heart transplants, and 7 left ventricular assist device implantations)
      during the 2-year tracking period. Receiver operating characteristic curve
      analysis revealed the overall VE/VCO2 slope classification scheme was significant
      (area under the curve: 0.78 [95% CI, 0.73 to 0.83], P<0.001). On the basis of
      test sensitivity and specificity, the following ventilatory class system was
      developed: (1) ventilatory class (VC) I: < or = 29; (2) VC II: 30.0 to 35.9; (3)
      VC III: 36.0 to 44.9; and (4) VC IV: > or = 45.0. The numbers of subjects in VCs
      I through IV were 144, 149, 112, and 43, respectively. Kaplan-Meier analysis
      revealed event-free survival for subjects in VC I, II, III, and IV was 97.2%,
      85.2%, 72.3%, and 44.2%, respectively (log-rank 86.8; P<0.001). CONCLUSIONS: A
      multiple-level classificatory system based on exercise VE/VCO2 slope stratifies
      the burden of risk for the entire spectrum of heart failure severity. Application
      of this classification is therefore proposed to improve clinical decision making
      in heart failure.

PMID- 17452608
TI  - Brachial flow-mediated dilation predicts incident cardiovascular events in older
      adults: the Cardiovascular Health Study.
AB  - BACKGROUND: The relationship between impaired brachial flow-mediated dilation
      (FMD) and subsequent clinical cardiovascular events is not well established,
      especially in older adults whose FMD is often diminished. We assessed the
      hypothesis that FMD predicts incident cardiovascular events in a population-based
      cohort of older adults. METHODS AND RESULTS: FMD was measured at the 1997 to 1998
      Cardiovascular Health Study clinic visit in 2792 adults aged 72 to 98 years
      (82.7% white, 58.6% women) recruited at 4 clinic sites in the United States. Log
      rank test and Cox proportional hazard models were used to examine the association
      between FMD and adjudicated cardiovascular events. A total of 674 subjects
      (24.1%) had an adjudicated event over the 5-year follow-up period. Event-free
      survival rates for cardiovascular events were significantly higher in subjects
      with FMD greater than the sex-specific medians than in subjects with FMD less
      than or equal to the sex-specific medians (78.3% versus 73.6%, log-rank P=0.006).
      FMD remained a significant predictor of cardiovascular events after adjustment
      for age, gender, diabetes mellitus, cigarette smoking, systolic and diastolic
      blood pressure, baseline cardiovascular disease status, and total cholesterol
      (hazard ratio, 0.91 [95% CI, 0.83 to 0.99], P=0.02 per unit SD of FMD) but added
      only approximately 1% to the prognostic accuracy of the best Cox model. Brachial
      artery diameter was also predictive of CV events in the adjusted Cox proportional
      hazard model (hazard ratio, 1.12 [95% CI, 1.02 to 1.28], P=0.025) and also added
      approximately 1% to the accuracy of our best Cox model. CONCLUSIONS: FMD is a
      predictor of future cardiovascular events but adds very little to the prognostic
      accuracy of traditional cardiovascular risk scores/factors in older adults. FMD
      and brachial artery diameter may have similar predictive values for
      cardiovascular events in older adults.

PMID- 17452609
TI  - Incremental benefit and cost-effectiveness of high-dose statin therapy in high
      risk patients with coronary artery disease.
AB  - BACKGROUND: Recent clinical trials found that high-dose statin therapy, compared
      with conventional-dose statin therapy, reduces the risk of cardiovascular events
      in patients with acute coronary syndromes (ACS) and stable coronary artery
      disease (CAD). However, the actual benefit and cost-effectiveness of high-dose
      statin therapy are unknown. METHODS AND RESULTS: We designed a Markov model to
      compare daily high-dose with conventional-dose statin therapy for hypothetical 60
      year-old cohorts with ACS and stable CAD over patient lifetime. Pooled estimates
      for major clinical end points (all-cause mortality, myocardial infarction,
      stroke, rehospitalization, and revascularization) from relevant clinical trials
      were incorporated. Incremental benefit was quantified as quality-adjusted life
      years (QALYs). Threshold analyses determined at what price difference high-dose
      statins would yield incremental cost-effective ratios below $50,000, $100,000,
      and $150,000 per QALY gained. In ACS patients, a high-dose versus conventional
      dose statin strategy resulted in a gain of 0.35 QALYs. In threshold analyses, a
      high-dose statin strategy consistently yielded incremental cost-effective ratios
      below $30,000 per QALY even under conservative model assumptions. In stable CAD
      patients, a high-dose statin strategy yielded a gain of only 0.10 QALYs and was
      sensitive to model assumptions about statin efficacy. The daily cost difference
      between a high- and conventional-dose statin would need to be <$1.70, $2.65, and
      $3.55 to yield incremental cost-effective ratios below $50,000, $100,000, and
      $150,000 per QALY. CONCLUSIONS: High-dose statin therapy is potentially highly
      effective and cost-effective in patients with ACS. In patients with stable CAD,
      however, the cost-effectiveness of high-dose statin therapy is highly sensitive
      to model assumptions about statin efficacy and cost. Use of high-dose statins can
      be supported on health economic grounds in patients with ACS, but the case is
      less clear for patients with stable CAD.

PMID- 17452610
TI  - Evidence for microvascular dysfunction in hypertrophic cardiomyopathy: new
      insights from multiparametric magnetic resonance imaging.
AB  - BACKGROUND: Microvascular dysfunction in hypertrophic cardiomyopathy (HCM) may
      create an ischemic substrate conducive to sudden death, but it remains unknown
      whether the extent of hypertrophy is associated with proportionally poorer
      perfusion reserve. Comparisons between magnitude of hypertrophy, impairment of
      perfusion reserve, and extent of fibrosis may offer new insights for future
      clinical risk stratification in HCM but require multiparametric imaging with high
      spatial and temporal resolution. METHODS AND RESULTS: Degree of hypertrophy,
      myocardial blood flow at rest and during hyperemia (hMBF), and myocardial
      fibrosis were assessed with magnetic resonance imaging in 35 HCM patients (9
      [26%] male/26 female) and 14 healthy controls (4 [29%] male/10 female), aged 18
      to 78 years (mean+/-SD, 42+/-14 years) with the use of the American Heart
      Association left ventricular 16-segment model. Resting MBF was similar in HCM
      patients and controls. hMBF was lower in HCM patients (1.84+/-0.89 mL/min per
      gram) than in healthy controls (3.42+/-1.76 mL/min per gram, with a difference of
      -0.95+/-0.30 [SE] mL/min per gram; P<0.001) after adjustment for multiple
      variables, including end-diastolic segmental wall thickness (P<0.001). In HCM
      patients, hMBF decreased with increasing end-diastolic wall thickness (P<0.005)
      and preferentially in the endocardial layer. The frequency of endocardial hMBF
      falling below epicardial hMBF rose with wall thickness (P=0.045), as did the
      incidence of fibrosis (P<0.001). CONCLUSIONS: In HCM the vasodilator response is
      reduced, particularly in the endocardium, and in proportion to the magnitude of
      hypertrophy. Microvascular dysfunction and subsequent ischemia may be important
      components of the risk attributable to HCM.

PMID- 17452611
TI  - Images in cardiovascular medicine. Magnetic resonance imaging guiding pacemaker
      implantation for severe sinus node dysfunction due to cardiac involvement in
      Erdheim-Chester disease.

PMID- 17452612
TI  - Images in cardiovascular medicine. Metastatic extracavitary cardiac melanoma: the
      role of contemporary imaging techniques in diagnosis and surgical planning.

PMID- 17452613
TI  - Images in cardiovascular medicine. Percutaneous epicardial mapping and ablation
      of a posteroseptal accessory pathway.

PMID- 17452614
TI  - Letter by Vogt regarding article, "Reduction in the incidence of acute myocardial
      infarction associated with a citywide smoking ordinance".

PMID- 17452615
TI  - A view from Bosnia and Herzegovina. Interview by Emma Wilkinson.

PMID- 17452616
TI  - New international measuring stick for defining obesity in non-Europeans.

PMID- 17452617
TI  - Ambulatory blood pressure for cardiovascular risk stratification.

PMID- 17452618
TI  - Variable platelet response to aspirin and clopidogrel in atherothrombotic
      disease.

PMID- 17452619
TI  - Interventional electrophysiology and cardiac resynchronization therapy:
      delivering electrical therapies for heart failure.
AB  - Implantable devices have become a readily available option for patients with
      heart failure. Not only do these patients develop bradycardia and ventricular
      tachycardia, but their ventricular dysfunction can often improve with cardiac
      resynchronization therapy. However, this is a complex and rapidly developing
      clinical science for which the physician chooses techniques and selects patients
      on the basis of the results of clinical trials, clinical experience, and rapidly
      evolving tools. The results depend on the interplay of these complex variables.
      Placement of the left ventricular lead has forced the device physician to develop
      new skills and/or interdisciplinary relationships with physicians with vascular
      intervention, imaging, and surgical skills. Familiarity with the cardiac venous
      anatomy, occlusive venography, venoplasty, guide wire tools, guiding catheters,
      stenting, and new intracardiac visualization and magnetic intracardiac lead
      positioning tools are examples of just a few of the novel skills that are useful
      in the delivery of cardiac resynchronization therapy. Beyond implantation, these
      patients and devices require specialized follow-up with continued medical therapy
      and echo-guided adjustments of device programming. Finally, there are ongoing
      controversies and many as yet unanswered questions that are the subject of
      ongoing and planned clinical trials.

PMID- 17452620
TI  - Leading the elephant out of the corner: the future of health care: presidential
      address at the American Heart Association 2006 scientific sessions.

PMID- 17452621
TI  - JCS Prize. 2006 winner: Satomi Matsuoka.

PMID- 17452622
TI  - Epithelial tight junctions, gene expression and nucleo-junctional interplay.
AB  - Tight junctions are components of the junctional complex linking neighbouring
      epithelial cells and are important for barrier formation. Recent evidence
      suggests that tight junctions also participate in signal transduction mechanisms
      that regulate epithelial cell proliferation, gene expression, differentiation and
      morphogenesis. One important class of tight-junction-associated signal
      transduction mechanism is based on dual localisation of certain proteins both at
      junctions and in the nucleus. These proteins and their partners participate in
      various steps of gene expression, ranging from regulation of transcription and
      chromatin structure to mRNA processing and translation. In cancer tissues, their
      expression is often deregulated in a manner that suggests that tight junctions
      function as suppressors of proliferation and transformation.

PMID- 17452623
TI  - YWK-II protein as a novel G(o)-coupled receptor for Mullerian inhibiting
      substance in cell survival.
AB  - Mullerian inhibiting substance (MIS) has recently been implicated in multiple
      cellular functions including promotion of cell survival, but the receptor(s) and
      signaling pathways involved remain elusive. We have investigated the possibility
      of YWK-II protein, previously shown to interact physically with MIS and G(o)
      protein, being a receptor mediating the cell survival effect of MIS. In YWK-II
      overexpressing CHO cells, MIS activates the G(o)-coupled ERK1/2 signaling pathway
      and promotes cell survival with altered levels of p53 and caspase-3. YWK-II
      antibody is found to interfere with the ability of MIS to promote viability of
      mouse sperm and affect MIS-activated ERK1/2 phosphorylation. In vivo studies
      involving injection of YWK-II antibody into the seminiferous tubule of the mouse
      testis, where MIS is known to be produced, show significant reduction in the
      sperm count with accumulation of p53 and cleaved caspase-3 in testicular nuclei.
      Taken together, the present study has demonstrated a new G(o)-coupled receptor
      for MIS in mediating ERK1/2 activation leading to anti-apoptotic activity or cell
      survival.

PMID- 17452624
TI  - Traction force microscopy in Dictyostelium reveals distinct roles for myosin II
      motor and actin-crosslinking activity in polarized cell movement.
AB  - Continuous cell movement requires the coordination of protrusive forces at the
      leading edge with contractile forces at the rear of the cell. Myosin II is
      required to generate the necessary contractile force to facilitate retraction;
      however, Dictyostelium cells that lack myosin II (mhcA-) are still motile. To
      directly investigate the role of myosin II in contractility we used a gelatin
      traction force assay to measure the magnitude and dynamic redistribution of
      traction stresses generated by randomly moving wild-type, myosin II essential
      light chain null (mlcE-) and mhcA- cells. Our data show that for each cell type,
      periods of rapid, directed cell movement occur when an asymmetrical distribution
      of traction stress is present, in which traction stresses at the rear are
      significantly higher than those at the front. We found that the major
      determinants of cell speed are the rate and frequency at which traction stress
      asymmetry develops, not the absolute magnitude of traction stress. We conclude
      that traction stress asymmetry is important for rapid, polarized cell movement
      because high traction stresses at the rear promote retraction, whereas low
      traction at the front allows protrusion. We propose that myosin II motor activity
      increases the rate and frequency at which traction stress asymmetry develops,
      whereas actin crosslinking activity is important for stabilizing it.

PMID- 17452625
TI  - Acetylation regulates tropomyosin function in the fission yeast
      Schizosaccharomyces pombe.
AB  - Tropomyosin is an evolutionarily conserved alpha-helical coiled-coil protein that
      promotes and maintains actin filaments. In yeast, Tropomyosin-stabilised
      filaments are used by molecular motors to transport cargoes or to generate motile
      forces by altering the dynamics of filament growth and shrinkage. The
      Schizosaccharomyces pombe tropomyosin Cdc8 localises to the cytokinetic
      actomyosin ring during mitosis and is absolutely required for its formation and
      function. We show that Cdc8 associates with actin filaments throughout the cell
      cycle and is subjected to post-translational modification that does not vary with
      cell cycle progression. At any given point in the cell cycle 80% of Cdc8
      molecules are acetylated, which significantly enhances their affinity for actin.
      Reconstructions of electron microscopic images of actin-Cdc8 filaments establish
      that the majority of Cdc8 strands sit in the 'closed' position on actin
      filaments, suggesting a role in the regulation of myosin binding. We show that
      Cdc8 regulates the equilibrium binding of myosin to actin without affecting the
      rate of myosin binding. Unacetylated Cdc8 isoforms bind actin, but have a reduced
      ability to regulate myosin binding to actin. We conclude that although
      acetylation of Cdc8 is not essential, it provides a regulatory mechanism for
      modulating actin filament integrity and myosin function.

PMID- 17452626
TI  - TGFbeta3 inhibits E-cadherin gene expression in palate medial-edge epithelial
      cells through a Smad2-Smad4-LEF1 transcription complex.
AB  - Dissociation of medial-edge epithelium (MEE) during palate development is
      essential for mediating correct craniofacial morphogenesis. This phenomenon is
      initiated by TGFbeta3 upon adherence of opposing palatal shelves, because loss of
      E-cadherin causes the MEE seam to break into small epithelial islands. To
      investigate the molecular mechanisms that cause this E-cadherin loss, we isolated
      and cultured murine embryonic primary MEE cells from adhered or non-adhered
      palates. Here, we provide the first evidence that lymphoid enhancer factor 1
      (LEF1), when functionally activated by phosphorylated Smad2 (Smad2-P) and Smad4
      (rather than beta-catenin), binds with the promoter of the E-cadherin gene to
      repress its transcription in response to TGFbeta3 signaling. Furthermore, we
      found that TGFbeta3 signaling stimulates epithelial-mesenchymal transformation
      (EMT) and cell migration in these cells. LEF1 and Smad4 were found to be
      necessary for up-regulation of the mesenchymal markers vimentin and fibronectin,
      independently of beta-catenin. We proved that TGFbeta3 signaling induces EMT in
      MEE cells by forming activated transcription complexes of Smad2-P, Smad4 and LEF1
      that directly inhibit E-cadherin gene expression.

PMID- 17452627
TI  - The P2Y2 nucleotide receptor requires interaction with alpha v integrins to
      access and activate G12.
AB  - The P2Y2 nucleotide receptor (P2Y2R) interacts with alpha v integrins to activate
      G(o) and induce chemotaxis in human 1321N1 astrocytoma cells. In this study, it
      was determined that the P2Y2R also requires interaction with alpha v integrins to
      activate G12 and associated signaling pathways that control chemotaxis in 1321N1
      cells. Mutation of the Arg-Gly-Asp (RGD) integrin-binding sequence in the first
      extracellular loop of the human P2Y2R to Arg-Gly-Glu (RGE), which prevents
      integrin interaction, did not inhibit G(q) or ERK1/2 signaling by the P2Y2R
      agonist UTP but completely inhibited activation of G12 and G12-mediated events,
      including Rho activation, cofilin and myosin light chain-2 phosphorylation,
      stress fiber formation and chemotaxis towards UTP. The involvement of G12 in all
      these events was verified by using a dominant negative G alpha12 construct. G12
      activation by the P2Y2R also was inhibited by anti-alpha v beta5 integrin
      antibodies and alpha v integrin antisense oligonucleotides, suggesting that alpha
      v integrin activity and expression are required for the P2Y2R to activate G12. Co
      immunoprecipitation experiments confirmed that G alpha12 protein associates with
      the wild-type P2Y2R and with alpha v integrins but not with the RGE mutant P2Y2R
      or with alpha3 integrins. Collectively, these results suggest that alpha v
      integrin complexes provide the P2Y2R with access to G12, thereby allowing
      activation of this heterotrimeric G protein that controls actin cytoskeletal
      rearrangements required for chemotaxis.

PMID- 17452628
TI  - Self-association and BiP dissociation are not sufficient for activation of the ER
      stress sensor Ire1.
AB  - Ire1 is a type I transmembrane protein located on the endoplasmic reticulum (ER).
      Upon ER stress, Ire1 releases the ER chaperone BiP and self-associates. This
      activates Ire1 and triggers the unfolded protein response in the yeast
      Saccharomyces cerevisiae. We isolated and characterized an Ire1 luminal domain
      mutant lacking both the N-terminal and the juxtamembrane loosely folded
      subregions. Although this 'core' mutant was able to self-associate and failed to
      bind BiP even under nonstressed conditions, its activation was still dependent on
      ER stress. Furthermore, although substitution of Pro for Ser103 (S103P) in the
      luminal domain of full-length Ire1 caused neither BiP dissociation nor a change
      in self-association, the substitution in combination with the core mutation
      resulted in constitutive activation. This phenotype of the S103P mutation
      required a cluster of positively charged amino acid residues (Arg or Lys) located
      close to the mutation site in the Ire1 sequence. These observations indicate that
      in addition to BiP dissociation and self-association of Ire1, another unknown
      change on the luminal side is crucial for Ire1 activation.

PMID- 17452629
TI  - Transition from a nucleosome-based to a protamine-based chromatin configuration
      during spermiogenesis in Drosophila.
AB  - In higher organisms, the chromatin of sperm is organised in a highly condensed
      protamine-based structure. In pre-meiotic stages and shortly after meiosis,
      histones carry multiple modifications. Here, we focus on post-meiotic stages and
      show that also after meiosis, histone H3 shows a high overall methylation of K9
      and K27 and we hypothesise that these modifications ensure maintenance of
      transcriptional silencing in the haploid genome. Furthermore, we show that
      histones are lost during the early canoe stage and that just before this stage,
      hyper-acetylation of histone H4 and mono-ubiquitylation of histone H2A occurs. We
      believe that these histone modifications within the histone-based chromatin
      architecture may lead to better access of enzymes and chromatin remodellers. This
      notion is supported by the presence of the architectural protein CTCF, numerous
      DNA breaks, SUMO, UbcD6 and high content of ubiquitin, as well as testes-specific
      nuclear proteasomes at this time. Moreover, we report the first transition
      protein-like chromosomal protein, Tpl(94D), to be found in Drosophila. We propose
      that Tpl(94D)--an HMG box protein--and the numerous DNA breaks facilitate
      chromatin unwinding as a prelude to protamine and Mst77F deposition. Finally, we
      show that histone modifications and removal are independent of protamine
      synthesis.

PMID- 17452630
TI  - Poor prognosis in carcinoma is associated with a gene expression signature of
      aberrant PTEN tumor suppressor pathway activity.
AB  - Pathway-specific therapy is the future of cancer management. The oncogenic
      phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in solid
      tumors; however, currently, no reliable test for PI3K pathway activation exists
      for human tumors. Taking advantage of the observation that loss of PTEN, the
      negative regulator of PI3K, results in robust activation of this pathway, we
      developed and validated a microarray gene expression signature for
      immunohistochemistry (IHC)-detectable PTEN loss in breast cancer (BC). The most
      significant signature gene was PTEN itself, indicating that PTEN mRNA levels are
      the primary determinant of PTEN protein levels in BC. Some PTEN IHC-positive BCs
      exhibited the signature of PTEN loss, which was associated to moderately reduced
      PTEN mRNA levels cooperating with specific types of PIK3CA mutations and/or
      amplification of HER2. This demonstrates that the signature is more sensitive
      than PTEN IHC for identifying tumors with pathway activation. In independent data
      sets of breast, prostate, and bladder carcinoma, prediction of pathway activity
      by the signature correlated significantly to poor patient outcome. Stathmin,
      encoded by the signature gene STMN1, was an accurate IHC marker of the signature
      and had prognostic significance in BC. Stathmin was also pathway-pharmacodynamic
      in vitro and in vivo. Thus, the signature or its components such as stathmin may
      be clinically useful tests for stratification of patients for anti-PI3K pathway
      therapy and monitoring therapeutic efficacy. This study indicates that aberrant
      PI3K pathway signaling is strongly associated with metastasis and poor survival
      across carcinoma types, highlighting the enormous potential impact on patient
      survival that pathway inhibition could achieve.

PMID- 17452631
TI  - Circadian desynchronization of core body temperature and sleep stages in the rat.
AB  - Proper functioning of the human circadian timing system is crucial to physical
      and mental health. Much of what we know about this system is based on
      experimental protocols that induce the desynchronization of behavioral and
      physiological rhythms within individual subjects, but the neural (or extraneural)
      substrates for such desynchronization are unknown. We have developed an animal
      model of human internal desynchrony in which rats are exposed to artificially
      short (22-h) light-dark cycles. Under these conditions, locomotor activity, sleep
      wake, and slow-wave sleep (SWS) exhibit two rhythms within individual animals,
      one entrained to the 22-h light-dark cycle and the other free-running with a
      period >24 h (tau(>24 h)). Whereas core body temperature showed two rhythms as
      well, further analysis indicates this variable oscillates more according to the
      tau(>24 h) rhythm than to the 22-h rhythm, and that this oscillation is due to an
      activity-independent circadian regulation. Paradoxical sleep (PS), on the other
      hand, shows only one free-running rhythm. Our results show that, similarly to
      humans, (i) circadian rhythms can be internally dissociated in a controlled and
      predictable manner in the rat and (ii) the circadian rhythms of sleep-wake and
      SWS can be desynchronized from the rhythms of PS and core body temperature within
      individual animals. This model now allows for a deeper understanding of the human
      timekeeping mechanism, for testing potential therapies for circadian
      dysrhythmias, and for studying the biology of PS and SWS states in a
      neurologically intact model.

PMID- 17452632
TI  - European early modern humans and the fate of the Neandertals.
AB  - A consideration of the morphological aspects of the earliest modern humans in
      Europe (more than approximately 33,000 B.P.) and the subsequent Gravettian human
      remains indicates that they possess an anatomical pattern congruent with the
      autapomorphic (derived) morphology of the earliest (Middle Paleolithic) African
      modern humans. However, they exhibit a variable suite of features that are either
      distinctive Neandertal traits and/or plesiomorphic (ancestral) aspects that had
      been lost among the African Middle Paleolithic modern humans. These features
      include aspects of neurocranial shape, basicranial external morphology,
      mandibular ramal and symphyseal form, dental morphology and size, and
      anteroposterior dental proportions, as well as aspects of the clavicles,
      scapulae, metacarpals, and appendicular proportions. The ubiquitous and variable
      presence of these morphological features in the European earlier modern human
      samples can only be parsimoniously explained as a product of modest levels of
      assimilation of Neandertals into early modern human populations as the latter
      dispersed across Europe. This interpretation is in agreement with current
      analyses of recent and past human molecular data.

PMID- 17452633
TI  - Political polarization.
AB  - Failures of government policies often provoke opposite reactions from citizens;
      some call for a reversal of the policy, whereas others favor its continuation in
      stronger form. We offer an explanation of such polarization, based on a natural
      bimodality of preferences in political and economic contexts and consistent with
      Bayesian rationality.

PMID- 17452634
TI  - Pigeons combine compass and landmark guidance in familiar route navigation.
AB  - How do birds orient over familiar terrain? In the best studied avian species, the
      homing pigeon (Columba livia), two apparently independent primary mechanisms are
      currently debated: either memorized visual landmarks provide homeward guidance
      directly, or birds rely on a compass to home from familiar locations. Using
      miniature Global Positioning System tracking technology and clock-shift
      procedures, we set sun-compass and landmark information in conflict, showing that
      experienced birds can accurately complete their memorized routes by using
      landmarks alone. Nevertheless, we also find that route following is often
      consistently offset in the expected compass direction, faithfully reproducing the
      shape of the track, but in parallel. Thus, we demonstrate conditions under which
      compass orientation and landmark guidance must be combined into a system of
      simultaneous or oscillating dual control.

PMID- 17452635
TI  - Multiple molecular evidences for a living mammalian fossil.
AB  - Laonastes aenigmamus is an enigmatic rodent first described in 2005. Molecular
      and morphological data suggested that it is the sole representative of a new
      mammalian family, the Laonastidae, and a member of the Hystricognathi. However,
      the validity of this family is controversial because fossil-based phylogenetic
      analyses suggest that Laonastes is a surviving member of the Diatomyidae, a
      family considered to have been extinct for 11 million years. According to these
      data, Laonastes and Diatomyidae are the sister clade of extant Ctenodactylidae
      (i.e., gundies) and do not belong to the Hystricognathi. To solve the
      phylogenetic position of Laonastes, we conducted a large-scale molecular
      phylogeny of rodents. The analysis includes representatives of all major rodent
      taxonomic groups and was based on 5.5 kb of sequence data from four nuclear and
      two mitochondrial genes. To further validate the obtained results, a short
      interspersed element insertion analysis including 11 informative loci was also
      performed. Our molecular data based on sequence and short interspersed element
      analyses unambiguously placed Laonastes as a sister clade of gundies. All
      alternative hypotheses were significantly rejected based on Shimodaira-Hasegawa
      tests, supporting the idea that Laonastes does not belong to the Hystricognathi.
      Molecular dating analysis also supports an ancient divergence, approximately 44
      Mya ago, between Ctenodactylidae and Laonastes. These combined analyses support
      the hypothesis that Laonastes is indeed a living fossil. Protection of this
      surviving species would conserve an ancient mammalian family.

PMID- 17452636
TI  - Characterization of a UBC13 kinase in Plasmodium falciparum.
AB  - Protein kinases are generally recognized as attractive drug targets to treat a
      variety of human diseases. Recent analysis of the Plasmodium falciparum kinome
      identified several kinases that are entirely unique to Plasmodium species. The
      specific functions and targets of most of these enzymes remain largely unknown.
      Here, we have identified a P. falciparum kinase (PfPK9/PF13_0085 ORF) that does
      not cluster with any of the typical eukaryotic protein kinases. PfPK9 protein
      expression was induced approximately 18 h after red blood cell infection, and was
      mainly localized to the parasitophorous vacuolar membrane as well as the cytosol.
      Recombinant PfPK9 autophosphorylated in vitro and specifically phosphorylated the
      exogenous substrate histone H1, indicating that it is catalytically active.
      Phosphopeptide mapping studies showed that autophosphorylation occurred at three
      residues: T082, T265, and T269. We identified a P. falciparum homolog of the E2
      ubiquitin-conjugating enzyme 13 (UBC13) as an endogenous substrate for PfPK9.
      PfPK9 phosphorylated UBC13 at S106, a highly conserved residue among eukaryotic
      E2s, and suppressed its ubiquitin-conjugating activity. Our findings not only
      describe a previously uncharacterized Plasmodium kinase and its likely in vivo
      target, but also suggest that modulation of UBC13 activity by phosphorylation may
      be a common regulatory mechanism in eukaryotes.

PMID- 17452637
TI  - A monomeric G protein-coupled receptor isolated in a high-density lipoprotein
      particle efficiently activates its G protein.
AB  - G protein-coupled receptors (GPCRs) respond to a diverse array of ligands,
      mediating cellular responses to hormones and neurotransmitters, as well as the
      senses of smell and taste. The structures of the GPCR rhodopsin and several G
      proteins have been determined by x-ray crystallography, yet the organization of
      the signaling complex between GPCRs and G proteins is poorly understood. The
      observations that some GPCRs are obligate heterodimers, and that many GPCRs form
      both homo- and heterodimers, has led to speculation that GPCR dimers may be
      required for efficient activation of G proteins. However, technical limitations
      have precluded a definitive analysis of G protein coupling to monomeric GPCRs in
      a biochemically defined and membrane-bound system. Here we demonstrate that a
      prototypical GPCR, the beta2-adrenergic receptor (beta2AR), can be incorporated
      into a reconstituted high-density lipoprotein (rHDL) phospholipid bilayer
      particle together with the stimulatory heterotrimeric G protein, Gs. Single
      molecule fluorescence imaging and FRET analysis demonstrate that a single beta2AR
      is incorporated per rHDL particle. The monomeric beta2AR efficiently activates Gs
      and displays GTP-sensitive allosteric ligand-binding properties. These data
      suggest that a monomeric receptor in a lipid bilayer is the minimal functional
      unit necessary for signaling, and that the cooperativity of agonist binding is
      due to G protein association with a receptor monomer and not receptor
      oligomerization.

PMID- 17452638
TI  - Nonrandom variations in human cancer ESTs indicate that mRNA heterogeneity
      increases during carcinogenesis.
AB  - Virtually all cancer biological attributes are heterogeneous. Because of this, it
      is currently difficult to reconcile results of cancer transcriptome and proteome
      experiments. It is also established that cancer somatic mutations arise at rates
      higher than suspected, but yet are insufficient to explain all cancer cell
      heterogeneity. We have analyzed sequence variations of 17 abundantly expressed
      genes in a large set of human ESTs originating from either normal or cancer
      samples. We show that cancer ESTs have greater variations than normal ESTs for
      >70% of the tested genes. These variations cannot be explained by known and
      putative SNPs. Furthermore, cancer EST variations were not random, but were
      determined by the composition of the substituted base (b0) as well as that of the
      bases located upstream (up to b - 4) and downstream (up to b + 3) of the
      substitution event. The replacement base was also not randomly selected but
      corresponded in most cases (73%) to a repetition of b - 1 or of b + 1. Base
      substitutions follow a specific pattern of affected bases: A and T substitutions
      were preferentially observed in cancer ESTs. In contrast, cancer somatic
      mutations [Sjoblom T, et al. (2006) Science 314:268-274] and SNPs identified in
      the genes of the current study occurred preferentially with C and G. On the basis
      of these observations, we developed a working hypothesis that cancer EST
      heterogeneity results primarily from increased transcription infidelity.

PMID- 17452639
TI  - An information-theoretic framework for resolving community structure in complex
      networks.
AB  - To understand the structure of a large-scale biological, social, or technological
      network, it can be helpful to decompose the network into smaller subunits or
      modules. In this article, we develop an information-theoretic foundation for the
      concept of modularity in networks. We identify the modules of which the network
      is composed by finding an optimal compression of its topology, capitalizing on
      regularities in its structure. We explain the advantages of this approach and
      illustrate them by partitioning a number of real-world and model networks.

PMID- 17452640
TI  - Physical interaction between the serotonin transporter and neuronal nitric oxide
      synthase underlies reciprocal modulation of their activity.
AB  - The spatiotemporal regulation of neurotransmitter transporters involves proteins
      that interact with their intracellular domains. Using a proteomic approach, we
      identified several proteins that interact with the C terminus of the serotonin
      transporter (SERT). These included neuronal nitric oxide synthase (nNOS), a PSD
      95/Disc large/ZO-1 (PDZ) domain-containing protein recruited by the atypical PDZ
      binding motif of SERT. Coexpression of nNOS with SERT in HEK293 cells decreased
      SERT cell surface localization and 5-hydroxytryptamine (5-HT) uptake. These
      effects were absent in cells transfected with SERT mutated in its PDZ motif to
      prevent physical association with nNOS, and 5-HT uptake was unaffected by
      activation or inhibition of nNOS enzymatic activity. 5-HT uptake into brain
      synaptosomes was increased in both nNOS-deficient and wild-type mice i.v.
      injected with a membrane-permeant peptidyl mimetic of SERT C terminus, which
      disrupted interaction between SERT and nNOS, suggesting that nNOS reduces SERT
      activity in vivo. Furthermore, treating cultured mesencephalic neurons with the
      mimetic peptide similarly increased 5-HT uptake. Reciprocally, indicating that 5
      HT uptake stimulates nNOS activity, NO production was enhanced on exposure of
      cells cotransfected with nNOS and SERT to 5-HT. This effect was abolished by 5-HT
      uptake inhibitors and absent in cells expressing SERT mutated in its PDZ motif.
      In conclusion, physical association between nNOS and SERT provides a molecular
      substrate for their reciprocal functional modulation. In addition to showing that
      nNOS controls cell surface localization of SERT, these findings provide evidence
      for regulation of cellular signaling (NO production) by a substrate-carrying
      transporter.

PMID- 17452641
TI  - Targeting the beta-catenin/TCF transcriptional complex in the treatment of
      multiple myeloma.
AB  - Multiple myeloma (MM) is an invariably fatal form of cancer characterized by
      clonal proliferation of malignant plasma cells in the bone marrow. The canonical
      Wnt signaling pathway is activated in MM cells through constitutively active beta
      catenin, a messenger molecule relevant to growth, survival, and migration of MM
      cells. The identification of a number of small molecular compounds, such as
      PKF115-584, which disrupt the interaction of the transcriptionally active beta
      catenin/TCF protein complex, provides valuable new therapeutic tools to target an
      alternative pathway in MM independent of the proteasome. Here we evaluated the
      transcriptional, proteomic, signaling changes, and biological sequelae associated
      with the inhibition of Wnt signaling in MM by PKF115-584. The compound blocks
      expression of Wnt target genes and induces cytotoxicity in both patient MM cells
      and MM cell lines without a significant effect in normal plasma cells. In
      xenograft models of human MM, PKF115-584 inhibits tumor growth and prolongs
      survival. Taken together, these data demonstrate the efficacy of disrupting the
      beta-catenin/TCF transcriptional complex to exploit tumor dependence on Wnt
      signaling as a therapeutic approach in the treatment of MM.

PMID- 17452642
TI  - The cidA murein hydrolase regulator contributes to DNA release and biofilm
      development in Staphylococcus aureus.
AB  - The Staphylococcus aureus cidA and lrgA genes have been shown to affect cell
      lysis under a variety of conditions during planktonic growth. It is hypothesized
      that these genes encode holins and antiholins, respectively, and may serve as
      molecular control elements of bacterial cell lysis. To examine the biological
      role of cell death and lysis, we studied the impact of the cidA mutation on
      biofilm development. Interestingly, this mutation had a dramatic impact on
      biofilm morphology and adherence. The cidA mutant (KB1050) biofilm exhibited a
      rougher appearance compared with the parental strain (UAMS-1) and was less
      adherent. Propidium iodide staining revealed that KB1050 accumulated more dead
      cells within the biofilm population relative to UAMS-1, indicative of reduced
      cell lysis. In agreement with this finding, quantitative real-time PCR
      experiments demonstrated the presence of 5-fold less genomic DNA in the KB1050
      biofilm relative to UAMS-1. Furthermore, treatment of the UAMS-1 biofilm with
      DNase I caused extensive cell detachment, whereas similar treatment of the KB1050
      biofilm had only a modest effect. These results demonstrate that cidA-controlled
      cell lysis plays a significant role during biofilm development and that released
      genomic DNA is an important structural component of S. aureus biofilm.

PMID- 17452643
TI  - Fatal gastrointestinal obstruction and hypertension in mice lacking nitric oxide
      sensitive guanylyl cyclase.
AB  - The signaling molecule nitric oxide (NO), first described as endothelium-derived
      relaxing factor (EDRF), acts as physiological activator of NO-sensitive guanylyl
      cyclase (NO-GC) in the cardiovascular, gastrointestinal, and nervous systems.
      Besides NO-GC, other NO targets have been proposed; however, their particular
      contribution still remains unclear. Here, we generated mice deficient for the
      beta1 subunit of NO-GC, which resulted in complete loss of the enzyme. GC-KO mice
      have a life span of 3-4 weeks but then die because of intestinal dysmotility;
      however, they can be rescued by feeding them a fiber-free diet. Apparently, NO-GC
      is absolutely vital for the maintenance of normal peristalsis of the gut. GC-KO
      mice show a pronounced increase in blood pressure, underlining the importance of
      NO in the regulation of smooth muscle tone in vivo. The lack of an NO effect on
      aortic relaxation and platelet aggregation confirms NO-GC as the only NO target
      regulating these two functions, excluding cGMP-independent mechanisms. Our
      knockout model completely disrupts the NO/cGMP signaling cascade and provides
      evidence for the unique role of NO-GC as NO receptor.

PMID- 17452644
TI  - Transmembrane protein Sun2 is involved in tethering mammalian meiotic telomeres
      to the nuclear envelope.
AB  - Dynamic repositioning of telomeres is a unique feature of meiotic prophase I that
      is highly conserved among eukaryotes. At least in fission yeast it was shown to
      be required for proper alignment and recombination of homologous chromosomes. On
      entry into meiosis telomeres attach to the nuclear envelope and transiently
      cluster at a limited area to form a chromosomal bouquet. Telomere clustering is
      thought to promote chromosome recognition and stable pairing of the homologs.
      However, the molecular basis of telomere attachment and movement is largely
      unknown. Here we report that mammalian SUN-domain protein Sun2 specifically
      localizes to the nuclear envelope attachment sites of meiotic telomeres. Sun2
      telomere association is maintained throughout the dynamic movement of telomeres.
      This association does not require the assembly of chromosomal axial elements or
      the presence of A-type lamins. Detailed EM analysis revealed that Sun2 is part of
      a membrane-spanning fibrillar complex that interconnects attached telomeres with
      cytoplasmic structures. Together with recent findings in fission yeast, our study
      indicates that the molecular mechanisms required for tethering meiotic telomeres
      and their dynamic movements during bouquet formation are conserved among
      eukaryotes.

PMID- 17452645
TI  - Synchronous cycles of domestic dog rabies in sub-Saharan Africa and the impact of
      control efforts.
AB  - Rabies is a fatal neurological pathogen that is a persistent problem throughout
      the developing world where it is spread primarily by domestic dogs. Although the
      disease has been extensively studied in wildlife populations in Europe and North
      America, the dynamics of rabies in domestic dog populations has been almost
      entirely neglected. Here, we demonstrate that rabies epidemics in southern and
      eastern Africa cycle with a period of 3-6 years and show significant synchrony
      across the region. The observed period is shorter than predictions based on
      epidemiological parameters for rabies in domestic dogs. We find evidence that
      rabies prevention measures, including vaccination, are affected by disease
      prevalence and show that a simple model with intervention responses can capture
      observed disease periodicity and host dynamics. We suggest that movement of
      infectious or latent animals combined with coordinated control responses may be
      important in coupling populations and generating synchrony at the continental
      scale. These findings have important implications for rabies prediction and
      control: large-scale synchrony and the importance of intervention responses
      suggest that control of canine rabies in Africa will require sustained efforts
      coordinated across political boundaries.

PMID- 17452646
TI  - Demonstration of artificial visual percepts generated through thalamic
      microstimulation.
AB  - Electrical stimulation of the visual system might serve as the foundation for a
      prosthetic device for the blind. We examined whether microstimulation of the
      dorsal lateral geniculate nucleus of the thalamus can generate localized visual
      percepts in alert monkeys. To assess electrically generated percepts, an eye
      movement task was used with targets presented on a computer screen (optically) or
      through microstimulation of the lateral geniculate nucleus (electrically).
      Saccades (fast, direct eye movements) made to electrical targets were comparable
      to saccades made to optical targets. Gaze locations for electrical targets were
      well predicted by measured visual response maps of cells at the electrode tips.
      With two electrodes, two distinct targets could be independently created. A
      sequential saccade task verified that electrical targets were processed not in
      motor coordinates, but in visual spatial coordinates. Microstimulation produced
      predictable visual percepts, showing that this technique may be useful for a
      visual prosthesis.

PMID- 17452647
TI  - Bradykinin B1 and B2 receptors both have protective roles in renal
      ischemia/reperfusion injury.
AB  - To explore the role of the kallikrein-kinin system in relation to
      ischemia/reperfusion injury in the kidney, we generated mice lacking both the
      bradykinin B1 and B2 receptor genes (B1RB2R-null, Bdkrb1-/-/Bdkrb2-/-) by
      deleting the genomic region encoding the two receptors. In 4-month-old mice,
      blood pressures were not significantly different among B1RB2R-null, B2R-null
      (Bdkrb2-/-), and WT mice. After 30 min of bilateral renal artery occlusion and 24
      h of reperfusion, mortality rates, renal histological and functional changes, 8
      hydroxy-2'-deoxyguanosine levels in total DNA, mtDNA deletions, and the number of
      TUNEL-positive cells in the kidneys increased progressively in the following
      order (from lowest to highest): WT, B2R-null, and B1RB2R-null mice. Increases in
      mRNA levels of TGF-beta1, connective tissue growth factor, and endothelin-1 after
      ischemia/reperfusion injury were also exaggerated in the same order (from lowest
      to highest): WT, B2R-null, and B1RB2R-null. Thus, both the B1 and B2 bradykinin
      receptors play an important role in reducing DNA damage, apoptosis, morphological
      and functional kidney changes, and mortality during renal ischemia/reperfusion
      injury.

PMID- 17452648
TI  - BetaKlotho is required for metabolic activity of fibroblast growth factor 21.
AB  - Fibroblast growth factor 21 (FGF21) is a liver-derived endocrine factor that
      stimulates glucose uptake in adipocytes. Here, we show that FGF21 activity
      depends on betaKlotho, a single-pass transmembrane protein whose expression is
      induced during differentiation from preadipocytes to adipocytes. BetaKlotho
      physically interacts with FGF receptors 1c and 4, thereby increasing the ability
      of these FGF receptors to bind FGF21 and activate the MAP kinase cascade.
      Knockdown of betaKlotho expression by siRNA in adipocytes diminishes glucose
      uptake induced by FGF21. Importantly, administration of FGF21 into mice induces
      MAP kinase phosphorylation in white adipose tissue and not in tissues without
      betaKlotho expression. Thus, betaKlotho functions as a cofactor essential for
      FGF21 activity.

PMID- 17452649
TI  - On-beam synchrony in the cerebellum as the mechanism for the timing and
      coordination of movement.
AB  - In trained reaching rats, we recorded simple spikes of pairs of Purkinje cells
      that, with respect to each other, were either aligned on a beam of shared
      parallel fibers or instead were located off beam. Rates of simple spike firing in
      both on-beam and off-beam Purkinje cell pairs commonly showed great variety in
      depth of modulation during reaching behavior. But with respect to timing, on-beam
      Purkinje cell pairs had simple spikes that were tightly time-locked to each other
      (either delayed or simultaneous) and to movement, despite the variability in
      rate. By contrast, off-beam Purkinje cell pairs had simple spikes that were not
      time-locked to each other, neither delayed nor simultaneous. We discuss the
      implications of these observations for the cerebellar role in timing and
      coordinating movement.

PMID- 17452650
TI  - Water surface is acidic.
AB  - Water autoionization reaction 2H2O --> H3O- + OH- is a textbook process of basic
      importance, resulting in pH = 7 for pure water. However, pH of pure water surface
      is shown to be significantly lower, the reduction being caused by proton
      stabilization at the surface. The evidence presented here includes ab initio and
      classical molecular dynamics simulations of water slabs with solvated H3O+ and OH
      ions, density functional studies of (H2O)(48)H+ clusters, and spectroscopic
      isotopic-exchange data for D2O substitutional impurities at the surface and in
      the interior of ice nanocrystals. Because H3O+ does, but OH- does not, display
      preference for surface sites, the H2O surface is predicted to be acidic with pH <
      4.8. For similar reasons, the strength of some weak acids, such as carbonic acid,
      is expected to increase at the surface. Enhanced surface acidity can have a
      significant impact on aqueous surface chemistry, e.g., in the atmosphere.

PMID- 17452652
TI  - Canada's fevered failure on malaria.

PMID- 17452653
TI  - Health Canada proposes new regulatory regime for drugs.

PMID- 17452651
TI  - Phase II study of metronomic chemotherapy for recurrent malignant gliomas in
      adults.
AB  - Preclinical evidence suggests that continuous low-dose daily (metronomic)
      chemotherapy may inhibit tumor endothelial cell proliferation (angiogenesis) and
      prevent tumor growth. This phase II study evaluated the feasibility of this
      antiangiogenic chemotherapy regimen in adults with recurrent malignant gliomas.
      The regimen consisted of low-dose etoposide (35 mg/m2 [maximum, 100 mg/day] daily
      for 21 days), alternating every 21 days with cyclophosphamide (2 mg/kg [maximum,
      100 mg/day] daily for 21 days), in combination with daily thalidomide and
      celecoxib, in adult patients with recurrent malignant gliomas. Serum and urine
      samples were collected for measurement of angiogenic peptides. Forty-eight
      patients were enrolled (15 female, 33 male). Twenty-eight patients had
      glioblastoma multiforme (GBMs), and 20 had anaplastic gliomas (AGs). Median age
      was 53 years (range, 33-74 years), and median KPS was 70 (range, 60-100). Therapy
      was reasonably well tolerated in this heavily pretreated population. Two percent
      of patients had partial response, 9% had a minor response, 59% had stable
      disease, and 30% had progressive disease. For GBM patients, median progression
      free survival (PFS) was 11 weeks, six-month PFS (6M-PFS) was 9%, and median
      overall survival (OS) was 21 weeks. For AG patients, median PFS was 14 weeks, 6M
      PFS was 26%, and median OS was 41.5 weeks. In a limited subset of patients, serum
      and urine angiogenic peptides did not correlate with response or survival (p >
      0.05). Although there were some responders, this four-drug, oral metronomic
      regimen did not significantly improve OS in this heavily pretreated group of
      patients who were generally not eligible for conventional protocols. While
      metronomic chemotherapy may not be useful in patients with advanced disease,
      further studies using metronomic chemotherapy combined with more potent
      antiangiogenic agents in patients with less advanced disease may be warranted.

PMID- 17452654
TI  - Need to lobby for access to asthma medications.

PMID- 17452655
TI  - UK doctors may lose self-regulation.

PMID- 17452658
TI  - A 48-year-old woman with lymphangioleiomyomatosis.

PMID- 17452659
TI  - Behcet's disease.

PMID- 17452660
TI  - Pathergy.

PMID- 17452661
TI  - The influence of a disaster on the health of rescue workers: a longitudinal
      study.
AB  - BACKGROUND: Rescue workers strive, after disasters, to help victims and restrict
      damage, often in dangerous circumstances. We examined the effect of a disaster on
      the physical and psychological health of rescue workers (firefighters, police
      officers and medical emergency services personnel) who provided assistance after
      the explosion of a fireworks depot in the Netherlands in May 2000. METHODS: We
      carried out a 4-year longitudinal study of 1403 rescue workers employed in or
      near the affected neighbourhood (the study group) and a control group of 1650
      uninvolved rescue workers (from another city of similar size and urbanization).
      Health outcomes were measured as prevalence, incidence (both measured as the
      percent of workers who took sick leave), frequency of the absences and number of
      sick days (both per 100 workers), and duration (mean length of sickness absences,
      in days). RESULTS: Sick leave among the study workers increased substantially
      during the 18 months after the explosion. For example, the prevalence of absences
      attributed to psychological problems increased from 2.5% of workers during the 6
      months before the disaster to 4.6% during the first 6-month period after the
      explosion and 5.1% during the second. That for respiratory problems rose from
      5.4% predisaster to 14.9% 6-12 months afterward. In comparison with controls,
      immediate increases occurred in musculoskeletal, psychological, respiratory and
      nonspecific ill health (e.g., malaise, fatigue) during the first year
      postdisaster. Rates of sick leave for musculoskeletal and respiratory reasons
      remained elevated until 3 years postdisaster, whereas leave for psychological
      problems and other ill health had returned to predisaster levels by then.
      Neurological problems increased after a 1-year delay. No significant increase in
      gastrointestinal problems was observed among the study workers, in comparison
      with controls. INTERPRETATION: Many health problems arise immediately after a
      disaster and may persist for years. Health care workers should realize, however,
      that some disaster-related effects may not emerge until a year or more after the
      event.

PMID- 17452662
TI  - The consequences of waiting for cataract surgery: a systematic review.
AB  - BACKGROUND: Cataract surgery is the most common operative procedure performed in
      Canada, and how patients are affected by wait times for this surgery has
      important clinical, public health and health policy considerations. We conducted
      a systematic review to understand the relation between wait time for cataract
      surgery and patient outcomes and the variables that modify this relation.
      METHODS: We performed an electronic search of 11 databases and the proceedings of
      4 conferences. The search was restricted to studies published after the
      transition to phacoemulsification (1990). We assessed the quality of the included
      studies using the Jadad Scale for randomized controlled trials and the Newcastle
      Ottawa Scale for cohort and case-control studies. The data were found to be
      inappropriate for meta-analysis, thus we performed a qualitative synthesis.
      RESULTS: We found a total of 27 studies that met our inclusion criteria. When
      these studies were reviewed, a dichotomy was observed for the wait time-outcome
      relation: outcomes associated with wait times of <or= 6 weeks were better than
      outcomes associated with wait times of >or= 6 months. Patients who waited more
      than 6 months to receive cataract surgery experienced more vision loss, a reduced
      quality of life and had an increased rate of falls compared with patients who had
      wait times of less than 6 weeks. The outcomes associated with wait times between
      6 weeks and 6 months remain unclear. INTERPRETATION: Patients who wait more than
      6 months for cataract surgery may experience negative outcomes during the wait
      period, including vision loss, a reduced quality of life and an increased rate of
      falls.

PMID- 17452663
TI  - The long-term health consequences of disasters and mass traumas.

PMID- 17452664
TI  - Evolution in the practice of pharmacy--not a revolution!

PMID- 17452665
TI  - Sleep and aging: 1. Sleep disorders commonly found in older people.
AB  - Aging is associated with several well-described changes in patterns of sleep.
      Typically, there is a phase advance in the normal circadian sleep cycle: older
      people tend to go to sleep earlier in the evening but also to wake earlier. They
      may also wake more frequently during the night and experience fragmented sleep.
      The prevalence of many sleep disorders increases with age. Insomnia, whether
      primary or secondary to coexistant illness or medication use, is very common
      among elderly people. Rapid eye movement (REM) sleep behaviour disorder and
      narcolepsy, although less common, are frequently not considered for this
      population. Periodic leg-movement disorder, a frequent cause of interrupted
      sleep, can be easily diagnosed with electromyography during nocturnal
      polysomnography. Restless legs syndrome, however, is diagnosed clinically.
      Snoring is a common sleep-related respiratory disorder; so is obstructive sleep
      apnea, which is increasingly seen among older people and is significantly
      associated with cardio-and cerebrovascular disease as well as cognitive
      impairment.

PMID- 17452666
TI  - Fundamental problem with opioid trials for chronic pain.

PMID- 17452668
TI  - Auricular acupuncture.

PMID- 17452669
TI  - Public involvement in guideline development.

PMID- 17452672
TI  - Sudden infant death syndrome.

PMID- 17452673
TI  - Clarification of the CMA's position concerning induced abortion.

PMID- 17452674
TI  - Problems with the progesterone receptor in practice?

PMID- 17452675
TI  - Lessons learned in the management of advanced pancreatic cancer.

PMID- 17452676
TI  - Efficacy of letrozole extended adjuvant therapy according to estrogen receptor
      and progesterone receptor status of the primary tumor: National Cancer Institute
      of Canada Clinical Trials Group MA.17.
AB  - PURPOSE: Controversy exists regarding estrogen (ER) and progesterone (PgR)
      receptor expression on efficacy of adjuvant endocrine therapy. In the ATAC
      (Arimidex, Tamoxifen, Alone or in Combination) trial, the benefit of anastrozole
      over tamoxifen was substantially greater in ER+/PgR-than ER+/PgR+ tumors. In BIG
      1-98 (Breast International Group), the benefits of letrozole over tamoxifen were
      the same in ER+ tumors irrespective of PgR. MA.17 randomized postmenopausal women
      after 5 years of tamoxifen, to letrozole or placebo. We present outcomes
      according to tumor receptor status. PATIENTS AND METHODS: Disease-free survival
      (DFS) and other outcomes were assessed in subgroups by ER and PgR status using
      Cox's proportional hazards model, adjusting for nodal status and prior adjuvant
      chemotherapy. RESULTS: The DFS hazard ratio (HR) for letrozole versus placebo in
      ER+/PgR+ tumors (N = 3,809) was 0.49 (95% CI, 0.36 to 0.67) versus 1.21 (95% CI,
      0.63 to 2.34) in ER+/PgR-tumors (n = 636). ER+/PgR+ letrozole patients
      experienced significant benefit in distant DFS (DDFS; HR = 0.53; 95% CI, 0.35 to
      0.80) and overall survival (OS; HR = 0.58; 95% CI, 0.37 to 0.90). A statistically
      significant difference in treatment effect between ER+/PgR+ and ER+/PgR-subgroups
      for DFS was observed (P = .02), but not for DDFS (P = .06) or OS (P = .09).
      CONCLUSION: These results suggest greater benefit for letrozole in DFS, DDFS, and
      OS in patients with ER+/PgR+ tumors, implying greater activity of letrozole in
      tumors with a functional ER. However, because this is a subset analysis and
      receptors were not measured centrally, we caution against using these results for
      clinical decision making.

PMID- 17452677
TI  - Erlotinib plus gemcitabine compared with gemcitabine alone in patients with
      advanced pancreatic cancer: a phase III trial of the National Cancer Institute of
      Canada Clinical Trials Group.
AB  - PURPOSE: Patients with advanced pancreatic cancer have a poor prognosis and there
      have been no improvements in survival since the introduction of gemcitabine in
      1996. Pancreatic tumors often overexpress human epidermal growth factor receptor
      type 1 (HER1/EGFR) and this is associated with a worse prognosis. We studied the
      effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in
      patients with unresectable, locally advanced, or metastatic pancreatic cancer.
      PATIENTS AND METHODS: Patients were randomly assigned 1:1 to receive standard
      gemcitabine plus erlotinib (100 or 150 mg/d orally) or gemcitabine plus placebo
      in a double-blind, international phase III trial. The primary end point was
      overall survival. RESULTS: A total of 569 patients were randomly assigned.
      Overall survival based on an intent-to-treat analysis was significantly prolonged
      on the erlotinib/gemcitabine arm with a hazard ratio (HR) of 0.82 (95% CI, 0.69
      to 0.99; P = .038, adjusted for stratification factors; median 6.24 months v 5.91
      months). One-year survival was also greater with erlotinib plus gemcitabine (23%
      v 17%; P = .023). Progression-free survival was significantly longer with
      erlotinib plus gemcitabine with an estimated HR of 0.77 (95% CI, 0.64 to 0.92; P
      = .004). Objective response rates were not significantly different between the
      arms, although more patients on erlotinib had disease stabilization. There was a
      higher incidence of some adverse events with erlotinib plus gemcitabine, but most
      were grade 1 or 2. CONCLUSION: To our knowledge, this randomized phase III trial
      is the first to demonstrate statistically significantly improved survival in
      advanced pancreatic cancer by adding any agent to gemcitabine. The recommended
      dose of erlotinib with gemcitabine for this indication is 100 mg/d.

PMID- 17452678
TI  - The reformation of sports medicine.

PMID- 17452684
TI  - Consensus statement on injury definitions and data collection procedures for
      studies of injuries in rugby union.
AB  - Wide variations in the definitions and methodologies used for studies of injuries
      in rugby union have created inconsistencies in reported data and made interstudy
      comparisons of results difficult. The International Rugby Board established a
      Rugby Injury Consensus Group (RICG) to reach an agreement on the appropriate
      definitions and methodologies to standardise the recording of injuries and
      reporting of studies in rugby union. The RICG reviewed the consensus definitions
      and methodologies previously published for football (soccer) at a meeting in
      Dublin in order to assess their suitability for and application to rugby union.
      Following this meeting, iterative draft statements were prepared and circulated
      to members of the RICG for comment; a follow-up meeting was arranged in Dublin,
      at which time all definitions and procedures were finalised. At this stage, all
      authors confirmed their agreement with the consensus statement. The agreed
      document was presented to and approved by the International Rugby Board Council.
      Agreement was reached on definitions for injury, recurrent injury, non-fatal
      catastrophic injury, and training and match exposures, together with criteria for
      classifying injuries in terms of severity, location, type, diagnosis and
      causation. The definitions and methodology presented in this consensus statement
      for rugby union are similar to those proposed for football. Adoption of the
      proposals presented in this consensus statement should ensure that more
      consistent and comparable results will be obtained from studies of injuries
      within rugby union.

PMID- 17452686
TI  - Flecainide cardiotoxicity precipitated by electrolyte imbalance. Caution with
      thiazide diuretics.
AB  - A man presented with recurrent syncope, weakness and fatigue. His ECG showed
      marked QRS widening and he had gross hyponatraemia and hypokalaemia. His
      medications included bendroflumethiazide (long term) and flecainide (started 2
      months previously). This presentation was consistent with flacainide
      cardiotoxicity exacerbated by electrolyte disturbance. The syncopal episodes
      probably represented life-threatening arrhythmias. The ECG and symptoms resolved
      completely once the electrolytes were corrected. Increased cardiotoxicity with
      hypokalaemia is documented, but not widely recognised. Hyponatraemia-induced
      flecainide cardiotoxicity has not been documented. The clinical effects of
      flecainide are due to use-dependent block of sodium channels. There are reports
      that support the use of hypertonic sodium salts to reverse flecainide toxicity
      via antagonism at the receptor. By this rationale, hyponatraemia would lead to
      Flecainide toxicity. Flecainide has been shown to reduce salt absorption in
      animal bowel. It is possible that in combination with bendroflumethiazide it
      acted synergistically to produce profound electrolyte disturbance. Flecainide
      cardiotoxicity has a significant mortality and can present non-specifically.
      Thus, early recognition is essential. This case demonstrates the importance of
      strict electrolyte control in patients who are on flecainide. We would discourage
      concomitant use of flecainide and bendroflumethiazide.

PMID- 17452687
TI  - Out-of-hospital use of intubating laryngeal mask airway for difficult intubation
      caused by cervical dislocation.

PMID- 17452688
TI  - An uncommon cause of epistaxis: cartoid cavernous fistula.
AB  - We report on an uncommon cause of epistaxis presenting to the emergency room.
      Epistaxis is not an uncommon presentation to emergency rooms across the world.
      The majority are easily controlled and have low mortality. We present a case of a
      carotid-cavernous fistula presenting with massive epistaxis culmination in
      cardiovascular collapse and death. Awareness of this entity will reduce the
      frequency of this condition resulting in major morbidity and mortality.

PMID- 17452689
TI  - A cause for concern? Osteopoikilosis found incidentally in the emergency
      department: a case report.
AB  - Osteopoikilosis is a rare, inherited bone disorder, which is usually found
      incidentally on x ray. It may be mistaken for other, more serious disorders such
      as bony metastases, causing undue distress to the doctor and patient.

PMID- 17452690
TI  - Acute myeloid leukaemia presenting as faecal incontinence.
AB  - Epidural sacral nerve compression as an initial feature of leukaemia is a rare
      complication. The findings in a 16-year-old boy who presented to an emergency
      department with symptoms of faecal incontinence are reported herein. Radiological
      imaging demonstrated soft-tissue masses in the sacral epidural space. The
      diagnosis of acute myeloid leukaemia was confirmed on bone marrow aspirate. The
      characteristics and management of extramedullary leukaemia are discussed.

PMID- 17452691
TI  - Death from paracetamol overdose despite appropriate treatment with N
      acetylcysteine.
AB  - A case of death from severe paracetamol poisoning which presented early and
      received appropriate treatment according to evidence-based guidelines is
      presented here. It is very rare for patients to die from paracetamol poisoning
      when they receive N-acetylcysteine (NAC) within 8 h of ingestion. The patient had
      a marked lactic acidosis on presentation to hospital. This case demonstrates that
      a patient can die from paracetamol poisoning despite early and appropriate
      treatment, and raises the question whether lactic acidosis in a patient following
      paracetamol overdose should prompt the initiation of NAC treatment while awaiting
      paracetamol levels.

PMID- 17452693
TI  - First do no harm; then try to prevent it.

PMID- 17452692
TI  - The use of a cardiac output monitor to guide the initial fluid resuscitation in a
      patient with burns.
AB  - A case of initial resuscitation of a patient with severe burns is described. Such
      patients can have hypotension and reduced organ perfusion for a number of
      reasons, and can remain in the emergency department for many hours while awaiting
      transfer to specialist centres. The case provides a comparison between
      resuscitation using traditional burns formulae and a relatively new and simple-to
      use cardiac output (CO) monitor--the Vigileo monitor (Edwards Lifesciences,
      Irvine, California, USA). The case demonstrates that relying on fluid regimes
      alone can lead to insufficient resuscitation. We suggest that using technologies
      such as those mentioned in this article, which have the potential to be used in
      the emergency department, could improve the initial resuscitation of patients
      with burns.

PMID- 17452694
TI  - Do we need new clinical standards in management of acute myocardial infarction?

PMID- 17452696
TI  - Recall after procedural sedation in the emergency department.
AB  - BACKGROUND: Procedural sedation (PS) is common in the emergency department (ED)
      and ideally patients should have no recall of the procedure. AIM: To determine
      the incidence of recall. METHODS: A prospective observational study in an
      university ED of all patients undergoing PS. Data were collected on a pre
      formatted data sheet. Levels of satisfaction with the sedation by the treating
      physician and nurse were recorded on a 10 cm visual analogue scale. On recovery,
      the patient was asked a validated questionnaire to determine the rate of
      immediate recall and at telephone follow-up for delayed recall. RESULTS: 125
      patients (88 male, 70%) were enrolled and 110 had completed follow-up. Mean
      (range) age was 51.6 (13-91) years. Procedures included 84 (67%) orthopaedic
      reductions and 41 (33%) cardioversions. A wide range of drug combinations were
      used, including fentanyl/propofol 32 (25.6%), fentanyl/midazolam 30 (24%),
      fentanyl/midazolam/propofol 16 (12.8%), propofol 13 (10.4%). 87.2% of procedures
      were successful. A grimace/groan was observed in 61 of 125 (49%). Immediate
      recall occurred in 9 of 121 (7.4%; 95% CI 3.7 to 14.0) and delayed recall in 5 of
      110 (4.5%; 95% CI 1.7 to 10.8). No drug combination was correlated with recall
      (Spearman's rho = 0.149), nor the presence of a grimace/groan (r = -0.039).
      Median sedation satisfaction scores were physician 9.0, nurse 10, patient 10.
      Correlation of delayed recall with patient satisfaction was -0.471 (p<0.001).
      CONCLUSIONS: Recall following PS in ED is uncommon. There is no association of
      recall with drugs used or the presence of a grimace/groan. There is high patient
      satisfaction with PS in the ED.

PMID- 17452695
TI  - A randomised, double-blind, placebo-controlled study to evaluate the role of
      formoterol in the management of acute asthma.
AB  - AIM: To evaluate the efficacy and tolerability of formoterol delivered by
      Aerolizer in the emergency department. METHODS: A single-centre, double-blind,
      randomised, placebo-controlled, parallel group study was conducted in patients
      seeking emergent care for an acute exacerbation of asthma. Patients were randomly
      assigned to one of two groups: group 1 (salbutamol), receiving a total dose of
      600 microg salbutamol (200+200+200) delivered by a meter-dose inhaler into a
      spacer device as two puffs at 20 min intervals; and group 2 (formoterol),
      receiving formoterol 24 microg (12+12) as two dry powder capsules each containing
      12 microg of formoterol via Aerolizer at 20 min intervals. The peak expiratory
      flow rate (PEFR) was measured at baseline and 5 min after the second and third
      doses. RESULTS: 60 subjects receiving salbutamol (n = 28) or formoterol (n = 32)
      completed the study. Age, gender, baseline PEFR, duration of asthma and previous
      medication were balanced between the two groups. Mean PEFR increased
      significantly over baseline values in both the salbutamol and formoterol groups
      (63% in the salbutamol group, p = 0.001, and 55% in the formoterol group, p =
      0.001). No significant difference was observed in the increase in PEFR between
      the groups (p = 0.99, 95% CI -29.62 to 29.59). The proportion of patients
      reporting adverse events was similar in the two groups. CONCLUSION: Formoterol
      was found to be well tolerated and as effective as salbutamol in the management
      of acute asthma. Further studies are needed to follow the patients after
      discharge from the emergency room to compare the long-term effect of formoterol
      on patients' stability.

PMID- 17452697
TI  - A study of blood product use in patients with major trauma in Scotland: analysis
      of a major trauma database.
AB  - OBJECTIVES: (1) To define blood product requirements in patients with trauma
      whose underlying injuries are consistent with major blood loss; (2) to use these
      data to estimate the annual number of patients in Scotland who sustain
      significant trauma and require substantial blood product replacement; and (3) to
      place these data in the context of recent findings concerning the efficacy of
      recombinant factor VIIa in patients with major trauma. METHODS: A retrospective
      case note review study was conducted for patients who presented with trauma at
      each of four Scottish hospitals. The four sites were selected from the 26
      hospitals that were the source of data for the Scottish Trauma Audit Group (STAG)
      database. Collected between 1991 and 2002, STAG encompasses approximately 53 000
      patients. 129 patients whose trauma codes were likely to be linked to injuries
      associated with major blood loss were selected. Data on the use of blood products
      for each patient were collected and analysed for three periods: (1) time spent in
      the emergency department (ED); (2) time from leaving the ED to the end of the
      first 24 h; and (3) time from the end of the first 24 h to 7 days. Blood product
      use for each period and for the entire first week of care was described for all
      patients and for blunt and penetrating injury subgroups. Using national
      population data estimates, the incidence of major trauma requiring blood
      transfusion was calculated for Scotland. RESULTS: Among the patients with trauma
      codes predicting significant blood loss, the proportion of patients requiring any
      blood transfusion within the first 7 days was 53.9%. 27.4% of patients received >
      or =8 units of red cell concentrate (RCC) within the first 24 h of
      hospitalisation. By direct extrapolation, we estimated that the annual number of
      Scotland's patients (aged >13 years) with a significant blood transfusion
      requirement secondary to traumatic injury was 67. Of these, 35 patients would
      require > or =8 units of RCC within the first 24 h. CONCLUSION: In summary, this
      study estimates that approximately 67 patients annually in Scotland, above the
      age of 13 years, require blood transfusion as a direct result of significant
      traumatic injury. Of these 67 patients, an estimated 35 patients (28 of whom had
      a blunt form of trauma) require > or =8 units of RCC during the first 24 h in
      hospital. On the basis of the current limited trial evidence, the potential
      benefit in using recombinant factor VIIa in such patients, in Scotland, is small
      approximately seven patients per million population aged >13 years, per year.

PMID- 17452698
TI  - A survey of information given to head-injured patients on direct discharge from
      emergency departments in Scotland.
AB  - AIM: To survey the information provided to head-injured patients on discharge
      from emergency departments (EDs) in Scotland. METHODS: EDs throughout Scotland
      were asked to supply a copy of their head injury advice pamphlet for analysis.
      Each pamphlet was assessed against a template and an Excel spreadsheet was
      created. RESULTS: All 30 (100%) Scottish EDs responded. The frequency with which
      specific features appeared varied widely, with most pamphlets concentrating on
      emergency features, with less emphasis on postconcussion symptoms. CONCLUSIONS:
      Head injury discharge advice should be standardised throughout EDs, with more
      emphasis given to postconcussion features.

PMID- 17452699
TI  - Identifying traumatic brain injury in patients with isolated head trauma: are
      arterial lactate and base deficit as helpful as in polytrauma?
AB  - BACKGROUND: Increase in lactate (LAC) within the central nervous system after
      head trauma is an established marker of traumatic brain injury (TBI). OBJECTIVE:
      To investigate the utility of arterial base deficit (BD) and LAC in identifying
      TBI in patients with isolated head injury (IHI). MATERIALS AND METHODS: TBI was
      defined as Glasgow Coma Scale < or =8, head Abbreviated Injury Severity Score >2
      or brain haematoma on CT scan. Patients were divided into two groups: IHI with
      and without TBI. Data were reported as means (SDs). 131 patients with IHI were
      studied (mean (SD) age 39 (19) years, 78% male). RESULTS: 17% of the patients
      sustained TBI. The mean differences for arterial BD (0.65 mmol/l, 95% CI -0.8 to
      2.1) and LAC (0.34 mmol/l, 95% CI -0.7 to 1.4) in patients with and without TBI
      were not significant. Analysis of receiver operating characteristic curves
      confirmed that arterial BD and LAC were unable to detect TBI in patients with
      IHI. CONCLUSION: Arterial BD and LAC are poor predictors of TBI in isolated head
      trauma.

PMID- 17452700
TI  - A simple screening tool for identification of community-acquired pneumonia in an
      inner city emergency department.
AB  - OBJECTIVES: To evaluate the performance of a simple screening tool for chest
      radiography for identification of community-acquired pneumonia (CAP) among
      emergency department (ED) patients who present with respiratory-related
      complaints. Our screening tool is a modification of a previously published
      guideline, which relied only on the presence of vital-sign abnormality (97%
      sensitivity, 19% specificity). We included respiratory symptoms to improve the
      specificity, defining our screening tool as the presence of any one respiratory
      symptom (cough, chest pain or shortness of breath) and any abnormality of the
      vital signs (temperature >38 degrees C, heart rate >100 beats/min, respiration
      rate >20 breaths/min, or pulse oximetry <95%). METHODS: This was a 3-month
      retrospective chart review of all ED visits from an inner city teaching hospital.
      CAP was defined as the presence of a new radiographic infiltrate compatible with
      CAP. Patients with asthma were excluded. RESULTS: Of 8811 patient visits
      evaluated, 1948 presented with a respiratory symptom. Of these, 198 had
      definitive CAP. Sensitivity, specificity, positive and negative predictive values
      of the ED screening tool were 90% (95% CI 85% to 94%), 76% (95% CI 74% to 78%),
      30% and 99%, respectively. Positive and negative likelihood ratios were 3.72 (95%
      CI 3.38 to 4.09) and 0.13 (95% CI 0.08 to 0.19), respectively. CONCLUSIONS: A
      simple screening tool with high sensitivity and specificity was used in an urban
      inner city ED to decide on the requirement for chest radiographs for patients
      with respiratory symptoms for identification of CAP. Validation studies are
      required to determine the utility of this screening tool for improving time to
      diagnosis and treatment.

PMID- 17452701
TI  - Emergency department follow-up of bereaved relatives: an audit of one particular
      service.
AB  - BACKGROUND: Although much has been written about the treatment of bereaved
      relatives in emergency departments, very little has been published about their
      follow-up after they have left the department. METHODS: One model of follow-up is
      described, in which relatives are invited to a meeting in the department 4-6
      weeks after their loss. In this model, it is emphasised that the follow-up is not
      a counselling session but an opportunity to ask questions, and an audit of the
      service is presented. RESULTS AND CONCLUSION: It is suggested that the provision
      of information is theoretically beneficial to the bereavement process.

PMID- 17452702
TI  - Cut-off values of B-type natriuretic peptide for the diagnosis of congestive
      heart failure in patients with dyspnoea visiting emergency departments: a study
      on Korean patients visiting emergency departments.
AB  - OBJECTIVES: To determine the optimal cut-off values of B-type natriuretic peptide
      (BNP) for the diagnosis of congestive heart failure (CHF) in 1040 Korean patients
      with dyspnoea visiting emergency departments. METHODS: BNP values were measured
      for 662 patients without CHF to examine whether significant relationships existed
      between the BNP values and age, gender or underlying disease. In 378 patients
      with CHF, a similar analysis was performed in addition to the examination of the
      relationship between the mean BNP values and CHF severity. RESULTS: The optimal
      threshold for the detection of heart failure was a BNP concentration of 296.5
      pg/mL, regardless of age, sex and underlying disease among the Korean study
      population. In the non-CHF patients, women showed significantly higher mean BNP
      values than did men. Further, in these patients, the mean BNP values of men with
      underlying disease (hypertension, angina pectoris, chronic renal failure, chronic
      obstructive pulmonary disease) and those with at least two underlying diseases,
      one of which was hypertension, was higher than those without underlying disease,
      whereas no difference was observed between women with and without underlying
      disease. Based on the New York Heart Association classification, echocardiography
      findings and mortality rate of the CHF patients, the BNP value was found to be
      related to both the severity of heart failure and its prognosis. CONCLUSIONS: The
      BNP concentration used for the diagnosis of CHF in Korean people is considerably
      higher than the normal cut-off value of 100 pg/mL. In the non-CHF patients, the
      BNP values of women were influenced less by underlying disease. This suggests
      that the factors that influence BNP values in women are different from those in
      men.

PMID- 17452704
TI  - Medical training in the UK fire service.
AB  - In 2005 the Faculty of Prehospital Care (Royal College of Surgeons of Edinburgh)
      were approached by two UK fire services for advice on trauma training relevant to
      their practice. No national standard was found regarding the medical knowledge,
      skills or equipment required for a UK firefighter. A paper survey was sent to the
      chief fire officer of the 62 fire services in the UK asking which medical skills
      were currently taught and practised in their service. The response rate was 84%
      and there was little consensus in utilised skills. The Faculty of Prehospital
      Care supports the development of a national standard and training model for
      medical training in the UK fire service, which should cover non-invasive
      techniques of resuscitation suggested in this article.

PMID- 17452703
TI  - Cardiac monitoring of high-risk patients after an electrical injury: a
      prospective multicentre study.
AB  - OBJECTIVE: To report our experience monitoring patients with previously
      identified theoretical risk factors of significant electrical injury. METHODS:
      Patients who presented to one of 21 emergency departments between October 2000
      and November 2004 were eligible to be enrolled in a prospective observational
      cohort study if after an electric shock they had one of several risk factors
      (transthoracic current, tetany, loss of consciousness or voltage source > or
      =1000 V) and therefore needed cardiac monitoring. RESULTS: Of the 134 patients
      enrolled, most were monitored because of transthoracic current (n = 60),
      transthoracic current and tetany (n = 39), tetany (n = 10), or voltage > or =1000
      V (n = 10). There were 15/134 (11%) patients with abnormal initial ECGs. No
      patient developed potentially lethal late arrhythmia during the 24 hours of
      cardiac monitoring. CONCLUSION: Although only patients deemed at risk of late
      arrhythmias were monitored, none developed potentially lethal late arrhythmias.
      Asymptomatic patients with transthoracic current and/or tetany and a normal
      initial ECG do not require cardiac monitoring after an electrical injury with
      voltage <1000 V and no loss of consciousness.

PMID- 17452705
TI  - Thyroid storm induced by trauma due to spear fishing-gun trident impaction in the
      neck.
AB  - A rare case of thyroid storm induced by thyroid gland injury because of
      penetrating neck trauma is reported. The injury was because of a spear fishing
      gun trident impaction in the neck. The diagnosis of thyroid gland injury was
      suspected by preoperative clinical examination and established during neck
      exploration in the theatre. The gland injury led to thyroid storm owing to the
      rupture of acini and liberation of T4 into the bloodstream. Withdrawal of the
      impacted trident along with subtotal thyroid lobectomy and repair of soft tissue
      damage in addition to supported treatments, which corrected the hyperthyroid
      state, led to uneventful recovery.

PMID- 17452706
TI  - Airway Scope versus Macintosh laryngoscope: a manikin study.
AB  - OBJECTIVE: To compare the performance of the Airway Scope for tracheal intubation
      with that of the Macintosh laryngoscope for direct laryngoscopy. METHODS: 10
      anaesthetists, 10 residents, 10 nurses and 10 students intubated the trachea of a
      manikin using the Airway Scope or the Macintosh laryngoscope in each of 4
      laryngoscopy scenarios. RESULTS: Within each group of operators, there was no
      significant difference in the time taken for intubation between the Airway Scope
      and the Macintosh laryngoscope. However, the overall number of teeth clicks was
      less in the Airway Scope, and the Airway Scope scored better on the visual
      analogue scale than did the Macintosh laryngoscope. CONCLUSION: The Airway Scope
      performed as well as and perhaps better than the Macintosh laryngoscope when used
      on a manikin.

PMID- 17452707
TI  - Ultrasound scanning in the diagnosis of acute appendicitis in pregnancy.

PMID- 17452709
TI  - Buscopan for oesophageal food bolus impaction.

PMID- 17452710
TI  - Atropine: re-evaluating its use during paediatric RSI.

PMID- 17452711
TI  - U cast or functional bracing following fractures of the shaft of humerus.

PMID- 17452712
TI  - Introduction of an electronic debrief and governance tool in prehospital care.
AB  - BACKGROUND: The Tayside Trauma Team is a mobile medical team that is deployed
      from Ninewells Hospital, Dundee, UK at the request of the ambulance service. AIM:
      To describe the implementation of a formal debrief and governance tool to ensure
      the ongoing provision of a high-quality prehospital service. METHODS: A
      questionnaire was devised to examine key issues relating to clinical governance
      and distributed to all members of staff involved in the provision of prehospital
      care. RESULTS: A number of areas of concern were revealed, including a lack of
      understanding on how to report critical incidents occurring in this field and a
      low level of opportunity to fully discuss events and vocalise concerns. These
      areas of concern were used to formulate an electronic debrief tool to be
      available to staff after each incident attended. Reports were considered and
      actioned and data collected for audit purposes and to provide a framework for
      discussion at monthly morbidity and mortality meetings. CONCLUSION: Any patient
      requiring the services of a healthcare professional in the prehospital setting
      has a right to expect the same level of quality of care that they would receive
      within the hospital. The development of a debrief tool will achieve ongoing
      quality of care in this specialised area of healthcare.

PMID- 17452713
TI  - Dissection of the carotid artery as a cause of fatal airway obstruction.
AB  - Carotid artery dissection is a rare entity, and most cases are attributable to
      causative factors, which include trauma and local malignancy. The vast majority
      of dissections present with cerebral infarct; those few that present with local
      mass effect and respiratory compromise may deteriorate rapidly, requiring urgent
      resuscitation and consideration of endotracheal intubation, which is often
      dangerous and/or impossible. The case of a spontaneous internal carotid artery
      dissection in an otherwise healthy young man, leading to gross mass effect and
      eventual fatal airway obstruction, is presented here. The need for a high index
      of suspicion for cervical vascular injury in cases of neck injury (even trivial),
      known head and neck malignancy/irradiation, or coagulopathy is highlighted.
      Patients presenting with unilateral neck swelling and symptoms related to mass
      effect must be assumed to have progressive airway obstruction, and difficult
      intubation should be anticipated.

PMID- 17452714
TI  - Small bowel obstruction.

PMID- 17452715
TI  - An unusual fracture of the scapular body.

PMID- 17452716
TI  - Trans-oculofacial injury from airgun pellet.

PMID- 17452717
TI  - Pneumothorax due to electrical burn injury.

PMID- 17452718
TI  - Technique for upgauging peripheral venous cannulae in volume resuscitation.

PMID- 17452719
TI  - Differences in trauma team activation criteria used by hospitals in the South
      West Peninsula.

PMID- 17452720
TI  - Reviewing blood test results: a worthwhile chore or a waste of time?

PMID- 17452721
TI  - Need for knowledge of local scanners for patients with morbid obesity.

PMID- 17452722
TI  - Liver rupture following delivery: HELLP needed.

PMID- 17452723
TI  - Retraction notice. Duplicate publication of short report.

PMID- 17452725
TI  - Liver X receptor alpha associates with human life span.
AB  - In the nematode Caenorhabditis elegans, nuclear hormone receptor DAF-12 regulates
      the decision to go into a resistant dauer diapause, in which the worm exhibits a
      decreased rate of aging. Using sequence similarity searches, we previously
      identified the liver X receptor alpha (LXRalpha) as one of the human nuclear
      hormone receptors the protein sequence of which is most similar to C. elegans DAF
      12. Here, we studied whether variation in the gene encoding LXRalpha associates
      with human life span. In the Leiden 85-Plus Study, a population-based prospective
      follow-up study, we genotyped four polymorphisms spanning the gene coding for
      LXRalpha (NR1H3) and tagged four common haplotypes. Among 563 participants,
      haplotype 2 associated with reduced mortality during the 7-year follow-up (hazard
      ratio 0.78; p =.015), predominantly caused by reduced mortality from infectious
      disease (hazard ratio 0.31; p =.023). Haplotype 2 also associated with higher
      levels of plasma apolipoprotein E, a target gene of the LXRalpha (p =.018), and
      higher levels of triglycerides (p =.041). Genetic variation in the gene coding
      for the LXRalpha (NR1H3) associates with human life span.

PMID- 17452726
TI  - Genetic association between Notch4 polymorphisms and Alzheimer's disease in the
      Japanese population.
AB  - It is shown that Notch 4 plays important roles in the pathogenesis of Alzheimer's
      disease (AD). To investigate whether three single nucleotide polymorphisms (SNPs)
      of the Notch4 gene are associated with AD, the three SNPs were genotyped by a
      polymerase chain reaction-restriction fragment length polymorphism method for 243
      AD patients and 130 age-matched controls. We also confirmed the linkage
      disequilibrium among these three SNPs of the gene using the EH program. The three
      SNPs did not seem to alter risk for AD. Our study suggests that SNPs studied are
      not associated with AD. The linkage disequilibrium of this locus indicates that
      there is genetic heterogeneity in the Notch4 gene. We could not confirm the
      previous synergetic associations of the 5' untranslated region (rs367398) C/C
      genotype in apolipoprotein E epsilon4 bearers in AD patients. Potential markers
      nearby the 5' untranslated region polymorphism might affect risk for AD.

PMID- 17452727
TI  - Dietary protein restriction decreases oxidative protein damage, peroxidizability
      index, and mitochondrial complex I content in rat liver.
AB  - Caloric restriction (CR) decreases oxidative damage, which contributes to the
      slowing of aging rate. It is not known if such decreases are due to calories
      themselves or specific dietary components. In this work, the ingestion of
      proteins of Wistar rats was decreased by 40% below that of controls. After 7
      weeks, the liver of the protein-restricted (PR) animals showed decreases in
      oxidative protein damage, degree of membrane unsaturation, and mitochondrial
      complex I content. The results and previous information suggest that the decrease
      in the rate of aging induced by PR can be due in part to decreases in
      mitochondrial reactive oxygen species production and DNA and protein oxidative
      modification, increases in fatty acid components more resistant to oxidative
      damage, and decreased expression of complex I, analogously to what occurs during
      CR. Recent studies suggest that those benefits of PR could be caused, in turn, by
      the lowered methionine intake of that dietary manipulation.

PMID- 17452728
TI  - Age-related changes in salivary antioxidant profile: possible implications for
      oral cancer.
AB  - Oral cancer's much higher prevalence among older people may be due to an age
      related reduction in protective salivary antioxidant mechanisms and/or an age
      related increase in the magnitude of oral carcinogen attack, such as reactive
      oxygen species (ROS) and reactive nitrogen species (RNS), causing DNA
      aberrations. This study found a significantly reduced total value of salivary
      antioxidant capacity in elderly persons (as measured by overall antioxidant
      capacity [ImAnOx] assay), (46% of healthy individuals, p =.004), increased
      oxidative stress (86% increase in carbonyl concentrations--indicators of enhanced
      ROS attack, p =.001), and increased salivary concentrations and total values of
      RNS (7-fold and 3-fold higher respectively, p =.001), all contributing to
      increased DNA oxidation of oral epithelial cells. Salivary oxidative stress
      related changes in the intimately related saliva and oral epithelium compounded
      with higher viscosity of saliva may explain the higher prevalence of oral cancer
      in the elderly population. Administration of local therapeutic agents (i.e.,
      antioxidants) to the oral cavity should be considered.

PMID- 17452729
TI  - Telomere dynamics in macaques and humans.
AB  - In humans, telomere length in proliferating tissues shortens with age--a process
      accelerated with age-related diseases. Thus, telomere length and attrition with
      age in the nonhuman primate may serve as a useful paradigm for understanding
      telomere biology in humans. We examined telomere parameters in tissues of young
      and old Macaca fascicularis and compared them with several tissues from humans.
      Macaque telomeres were variable in length and exhibited partial synchrony
      (equivalence) within animals. They were longer than humans, partially because of
      longer subtelomeric segments. As skeletal muscle telomere length was unchanged
      with age, we used it as an internal reference to offset interanimal variation in
      telomere length. We identified age-dependent telomere attrition in lung,
      pancreas, skin, and thyroid. Similar to humans, telomerase activity was detected
      in spleen, thymus, digestive tract, and gonads. We conclude that factors that
      modify telomere attrition and aging in humans may also operate in the macaque.

PMID- 17452730
TI  - Single skeletal muscle fiber elastic and contractile characteristics in young and
      older men.
AB  - The current investigation was designed to: (a) assess the impact of aging on
      elastic characteristics of single skeletal muscle fibers from young (N = 6) and
      older men (N = 6); and (b) correlate the potential changes, with the fiber
      contractile properties. Chemically skinned single muscle fibers (n = 235) from
      vastus lateralis muscle were maximally activated. Maximal force and cross
      sectional area were measured, and specific force calculated. The slack test was
      used to measure maximal unloaded shortening velocity. A quick release of 0.15% of
      fiber length was applied to determine instantaneous stiffness. The myosin heavy
      chain isoform composition of each single fiber was determined by sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Aging induces changes in
      both fiber elasticity (i.e., increased instantaneous stiffness) and contractility
      (i.e., reduced specific force and unloaded shortening velocity) in type I and IIa
      fibers. However, the changes in fiber stiffness may not directly influence
      contractile characteristics alterations.

PMID- 17452731
TI  - Aldosterone antagonism fails to attenuate age-associated left ventricular
      fibrosis.
AB  - Collagen accumulates disproportionately in cardiac remodeling induced by
      hypertension and associated with advancing age. Spironolactone (Spiro), an
      aldosterone antagonist, attenuates the accumulation of collagen induced by
      hypertension. It was hypothesized that Spiro would attenuate the age-associated
      increase in percent collagen in the heart. Female Fisher 344 rats at 3 months
      (Y), 12 months (M), and 21 months (O) of age were treated with Spiro (30 mg/kg/d)
      or vehicle (Veh) for 2 months, yielding six groups: Y-Veh, Y-Spiro, M-Veh, M
      Spiro, O-Veh, and O-Spiro. Hearts were harvested for immunoblotting, RNA
      blotting, and biochemical analysis. Percent collagen in the left ventricle and
      septum was greatest in the oldest rats. Spiro did not significantly attenuate the
      age-associated increase in collagen fraction or the age-associated increases in
      expression of atrial natriuretic factor and beta-myosin heavy chain messenger
      RNA. Chronic aldosterone antagonism does not attenuate the age-associated
      increase in collagen fraction in the female Fisher 344 rat heart.

PMID- 17452732
TI  - Improving end-of-life care for older adults: an international challenge.

PMID- 17452733
TI  - Prevalence of patients with do-not-resuscitate status on acute geriatric wards in
      Flanders, Belgium.
AB  - BACKGROUND: Elderly hospitalized patients have low survival rates after
      cardiopulmonary resuscitation, especially in the long term. This study aims to
      investigate the prevalence of patients with do-not-resuscitate (DNR) status on
      acute geriatric wards and the characteristics of the preceding decision-making
      process. METHODS: On all 94 geriatric wards in Flanders, Belgium (2002), the
      geriatrician who performed the bulk of clinical work was asked to fill in a
      retrospective structured mail questionnaire. RESULTS: The response rate was
      72.3%. A DNR status was attributed to 20.3% of patients. A significant higher
      prevalence of patients with DNR status was found on wards with a geriatrician who
      had been active in patient care for 15 years or less and on wards with a DNR
      policy. Mostly, DNR status was attributed when the patient's condition declined
      (34.0%) or became critical (29.0%). Geriatricians consulted at least one person
      in 81.0% of the cases: (head) nurses in 72.2%, next of kin in 61.9%, the
      patient's general practitioner in 22.6%, and the patient him- or herself in
      15.7%. Reasons stated to make a DNR decision were the prognosis (68.1%) and the
      physical condition of the patient (62.2%). Age was mentioned in only 21.1% of the
      cases, always in combination with other reasons. CONCLUSIONS: One fifth of
      patients on acute geriatric wards in Flanders have DNR status. The decision to
      attribute DNR status is most often made late in the course of the disease. (Head)
      nurses and the patient's next of kin are often consulted, the patient and his or
      her general practitioner rarely.

PMID- 17452734
TI  - Health care use at the end of life among older adults: does it vary by age?
AB  - BACKGROUND: Issues around end-of-life health care have attracted increasing
      attention in the last decade. One question that has arisen is whether very
      elderly individuals receive overly aggressive treatment at the end of life. The
      purpose of this study was to address this issue by examining whether health care
      use at the end life varies by age. METHODS: The study included all adults 65
      years old or older who died in Manitoba, Canada in 2000 (N = 7678). Measures were
      derived from administrative data files and included location of death,
      hospitalizations, intensive care unit (ICU) admission, long-term care (LTC) use,
      physician visits, and prescription drug use in the last 30 days versus 180 days
      before death, respectively. RESULTS: Individuals 85 years old or older had
      increased odds of being in a LTC institution and also dying there than did
      individuals 65-74 years old. They had, correspondingly, lower odds of being
      hospitalized and being admitted to an ICU. Although some statistically
      significant age differences emerged for physician visits, the effects were small.
      Prescription drug use did not vary by age. CONCLUSIONS: These findings indicate
      that very elderly individuals tended to receive care within LTC settings, with
      care that might be considered aggressive declining with increasing age. However,
      health care use among all age groups was substantial. A critical issue that needs
      to be examined in future research is how to ensure quality end-of-life care in a
      variety of clinical contexts and care settings for individuals of all ages.

PMID- 17452735
TI  - The burden of diseases on disability-free life expectancy in later life.
AB  - BACKGROUND: The consequences of diseases in later life have been judged
      predominantly through mortality, resulting in an emphasis on the fatal rather
      than the nonfatal disabling conditions. We use a longitudinal study with follow
      up at 2, 6, and 10 years to assess the impact of different diseases on both total
      life expectancy (TLE) and disability-free life expectancy (DFLE). METHODS: The
      Medical Research Council Cognitive Function and Ageing Study investigators
      interviewed 13,004 people aged 65 years and older from five U.K. centers starting
      in 1991. Persons aged 75 years and older were oversampled. Disability (mild,
      moderate, and severe) was assessed through basic Activities of Daily Living (ADL)
      and Instrumental ADL (IADL) scales at baseline and at follow-ups at 2, 6, and 10
      years. TLE and DFLE were compared for persons with and without each of nine
      conditions. RESULTS: At age 65, men had a TLE of 15.3 years of which 12.1 (79%)
      were free of any disability, whereas women of the same age had an average TLE of
      19.4 years, 11.0 years (57%) disability-free. Men (women) aged 65 years without
      stroke had 4.8 (4.6) more years of TLE and 6.5 (5.8) more years DFLE. Without
      diabetes, men (women) lived 4.4 (5.6) years longer and had 4.1 (5.1) years
      disability-free. CONCLUSIONS: More disability-free years were gained than total
      life years in persons free of stroke, cognitive impairment, arthritis, and/or
      visual impairment at baseline. This finding suggests that elimination of these
      conditions would result in a compression of disability.

PMID- 17452736
TI  - Utility of the mean cumulative function in the analysis of fall events.
AB  - BACKGROUND: Falls are the most common cause of injury among elderly people; half
      of those people fall recurrently. The objective of these simulation studies was
      to describe the Mean Cumulative Function (MCF) and to evaluate the utility of the
      MCF in detecting differences between groups experiencing different patterns of
      event intensities. METHODS: We specified 250 participants per group with a
      maximum follow-up time of 365 days. A participant could experience 0, 1, 2, 3, or
      4 falls. In the baseline experiment, Groups A and B had an average intensity of
      60 and 90 days to the first fall event. These event intensities remained constant
      for events 2-4. Group C represents a short term "strong" initial impact of the
      intervention modeled for falls 1 and 2, with an average intensity of one fall per
      117 days; however, the intervention wanes to "moderate" for falls 3 and 4 with an
      average intensity of one fall per 90 days. Group D represents a long-term
      "strong" impact of the intervention modeled by an average intensity of one fall
      per 117 days for all subsequent events. RESULTS: The MCF was able to detect
      differences between groups that had varying intensities of subsequent falls. In
      Group A, all participants experienced at least one fall, whereas Groups B, C, and
      D had 4, 9, and 15 participants, respectively, who did not experience any falls.
      The proportion of participants who had 4 falls declined from 84% to 40% in Groups
      A and D, respectively. When Group A was compared to Group D, the MCF difference
      detected the prevention of, on average, one fall per person within 175 days.
      Discussion. A novel instrument for this field of clinical research--the MCF-
      allows investigators to compare the average number of falls per participant when
      the intervention reduces the intensity of subsequent falls.

PMID- 17452737
TI  - Cytokines and C-reactive protein production in hip-fracture-operated elderly
      patients.
AB  - BACKGROUND: The study aim was to determine the kinetics of serum pro- and anti
      inflammatory cytokines and C-reactive protein (CRP) in hip-fracture patients over
      a month postfracture, and their relationship to postoperative (postop)
      complications and cognitive level. METHODS: Forty-one elderly hip-fracture
      patients were prospectively followed. Serum was obtained during the first 10
      hours postfracture and presurgery, 48-60 hours postop, 7 and 30 days postop,
      measuring CRP, interleukin-1beta (IL-1beta), IL-6, IL-8, tumor necrosis factor
      alpha (TNF-alpha), IL-10, and IL-1 receptor antagonist (IL-1RA). RESULTS: A
      significant increase was found postop for CRP, IL-6, TNF-alpha, IL-1RA (p <.001),
      IL-10 (p <.002), and IL-8 (p =.05). CRP kinetics curves were higher in patients
      with complications as a group, and in those suffering from infections, delirium,
      and cardiovascular complications (p <.05). IL-6 increase in patients with
      complications approached significance. Additional complications appeared in
      patients with impaired mental status (IMS) versus cognitively normal patients (p
      =.037). Higher kinetics curves in the IMS patients were found for CRP and IL-6 (p
      <.05). Analyzing the interaction effect of complications and IMS on CRP and
      cytokines production demonstrated that the increase in CRP was independently
      related to complications and IMS. IL-6, IL-8, and IL-10 were higher in IMS
      patients but not in patients with complications without IMS (p <.05).
      CONCLUSIONS: Serum CRP and cytokines increased drastically in postop hip-fracture
      elderly patients. Only CRP significantly and independently increased in IMS
      patients and in patients with complications, whereas cytokines significantly
      increased only in IMS patients. This study raises questions about possible
      effects that cytokine generation, after hip-fracture repair, might have on
      cognition and complications.

PMID- 17452738
TI  - Circulating glycotoxins and dietary advanced glycation endproducts: two links to
      inflammatory response, oxidative stress, and aging.
AB  - BACKGROUND: Oxidative stress (OS) and inflammatory mediators increase with aging.
      The levels of advanced glycation endproducts (AGEs), prooxidant factors linked to
      chronic diseases such as diabetes, cardiovascular disease, and renal disease,
      also increase with aging. AGEs are readily derived from heat-treated foods. We
      propose that the excess consumption of certain AGEs via the diet enhances OS and
      inflammatory responses in healthy adults, especially in elderly persons. METHODS:
      We examined 172 young (<45 years old) and older (>60 years old) healthy
      individuals to determine whether the concentration of specific serum AGEs
      (N(epsilon)-carboxymethyl-lysine [CML] or methylglyoxal [MG] derivatives) were
      higher in older compared to younger persons and whether, independent of age, they
      correlated with the intake of dietary AGEs, as well as with circulating markers
      of OS and inflammation. RESULTS: Body weight, body mass index (BMI), and serum
      AGE, CML, and MG derivatives were higher in older participants, independent of
      gender. Serum CML correlated with levels of 8-isoprostanes (r = 0.448, p =.0001)
      as well as with Homeostasis Model Assessment index (HOMA), an index of insulin
      resistance (r = 0.247, p =.044). The consumption of dietary AGEs, but not of
      calories, correlated independently with circulating AGEs (CML: r = 0.415, p
      =.0001 and MG: r = 0.282, p =.002) as well as with high sensitivity C-reactive
      protein (hsCRP) (r = 0.200, p =.042). CONCLUSIONS: Circulating indicators of AGEs
      (CML and MG derivatives), although elevated in older participants, correlate with
      indicators of inflammation and OS across all ages. Indicators of both AGEs and OS
      are directly influenced by the intake of dietary AGEs, independent of age or
      energy intake. Thus, reduced consumption of these oxidants may prove a safe
      economic policy to prevent age-related diseases, especially in an aging
      population.

PMID- 17452739
TI  - Relationship of homocysteine levels to quadriceps strength, gait speed, and late
      life disability in older adults.
AB  - BACKGROUND: Elevated homocysteine, causing tissue injury by such mechanisms as
      oxidative stress, endothelial damage, and protein homocysteinylation, is
      associated with multiple age-related problems including cardiovascular diseases,
      dementia, and osteoporotic fracture. Disability is one of the most common
      features in older adults. However, little is known about the role of homocysteine
      in physical disability among older adults. METHODS: Participants (>60 years, N =
      1677) were from the National Health and Nutrition Examination Survey (NHANES)
      1999-2002. Nineteen questionnaires in five major domains were administered to
      assess the level of difficulty in performing various tasks: activities of daily
      living (ADL), instrumental ADL (IADL), leisure and social activities (LSA), lower
      extremity mobility (LEM), and general physical activities (GPA). Peak quadriceps
      strength was obtained by using an isokinetic dynamometer. Habitual gait speed was
      obtained from a 20-foot timed walk. Homocysteine levels were measured by the
      Abbott homocysteine assay, an automated fluorescence polarization immunoassay
      (FPIA). RESULTS: Elevated homocysteine was associated with disability in ADL,
      IADL, LSA, and GPA after multivariate adjustment. The odds ratios (ORs) for
      disability in these domains comparing participants in the highest quartile of
      homocysteine to those in the lowest were 2.18 (95% confidence interval [CI], 1.32
      3.59) for ADL; 1.62 (95% CI, 1.02-2.57) for IADL; 2.00 (95% CI, 1.14-3.51) for
      LSA; and 1.52 (95% CI, 1.05-2.21) for GPA. The strength of associations weakened
      somewhat after additional adjustment of quadriceps strength and/or gait speed,
      suggesting a mediating role of quadriceps strength and gait speed in the
      association between homocysteine and disability. Homocysteine had an inverse
      relationship to quadriceps strength and gait speed. Likewise, quadriceps strength
      seemed to mediate the inverse association between homocysteine and gait speed.
      CONCLUSIONS: Elevated homocysteine is associated with multiple domains of
      disability mediated in part by muscle strength and gait speed. The results
      suggest that homocysteine levels may be important indicators of performance
      status in older adults.

PMID- 17452741
TI  - Genetic and environmental influences on hearing in older women.
AB  - BACKGROUND: This study examined the relative contribution of genetic and
      environmental effects on the air-conducted hearing threshold level (0.5-4 kHz)
      and speech recognition threshold level of the better ear as well as self-reported
      hearing in older women. METHODS: Hearing was measured as a part of the Finnish
      Twin Study on Aging in 103 monozygotic (MZ) and 114 dizygotic (DZ) female twin
      pairs aged 63-76 years. Audiometric measured hearing was tested using
      standardized methods in soundproof conditions. Self-reported hearing was assessed
      by a structured question. Quantitative genetic modeling was used for data
      analyses. RESULTS: No significant differences in age, exposure to noise, hearing
      aid use, auditory diseases or accidents, or number of self-reported chronic
      conditions or prescription medicines were observed between the MZ and DZ twins. A
      genetic component in common accounted for 75% (95% confidence interval [CI], 67%
      81%) of the variance in the better ear's hearing threshold level and 54% (95% CI,
      43%-64%) in the better ear's speech recognition threshold level, according to a
      bivariate genetic analysis. In addition, 10% (95% CI, 4%-15%) of the variance in
      the better ear's speech recognition threshold level was explained by its specific
      genetic component. CONCLUSION: Individual differences in audiometrically measured
      air-conducted hearing threshold level (0.5-4 kHz) and speech recognition
      threshold level in the better ear were largely accounted for by genetic
      differences between individuals. In contrast, self-reported hearing appears to be
      accounted for solely by environmental factors.

PMID- 17452742
TI  - Age-related changes in skeletal muscle as detected by diffusion tensor magnetic
      resonance imaging.
AB  - BACKGROUND: Loss of muscle mass and strength is a common symptom in the elderly
      population. This is partly a result of the structural changes that occur during
      the aging process. We applied diffusion tensor magnetic resonance imaging (DTMRI)
      to determine if water diffusivity in skeletal muscle changes with age. METHODS:
      Thirty-eight healthy men, ranging from 27 to 67 years of age, were recruited for
      this study. The total population was grouped by age (Young < mean age 46.4: n =
      20; Old > or = mean age 46.4: n = 18) and body mass index (BMI; Normal < 25: n =
      20; Over > or =25: n = 18). The principal, second, and third eigenvalues
      (lambda(1) > or = lambda(2) > or = lambda(3)), and fractional anisotropy (FA),
      were calculated from the diffusion tensor of the soleus, lateral and medial
      gastrocnemius, and anterior tibialis (AT). Analyses included comparison of groups
      and linear regressions. RESULTS: The older adults showed a significant reduction
      in the eigenvalues of the plantar flexors ( approximately 7%, p <.05) and FA of
      AT ( approximately 10%, p <.05) from that of the younger adults. No age
      differences were observed in the FA of the plantar flexors or eigenvalues of AT.
      lambda(1) and lambda(2) had a linear dependence on age in the plantar flexors,
      whereas AT showed age dependence in lambda(3) and FA. CONCLUSIONS: We
      demonstrated that DTMRI is sensitive to age-related changes in muscle, and that
      the effects of aging differ between the plantar flexors and AT.

PMID- 17452740
TI  - Association between vitamin D status and physical performance: the InCHIANTI
      study.
AB  - BACKGROUND: Vitamin D status has been hypothesized to play a role in
      musculoskeletal function. Using data from the InCHIANTI study, we examined the
      association between vitamin D status and physical performance. METHODS: A
      representative sample of 976 persons aged 65 years or older at study baseline
      were included. Physical performance was assessed using a short physical
      performance battery (SPPB) and handgrip strength. Multiple linear regression was
      used to examine the association between vitamin D (serum 25OHD), parathyroid
      hormone (PTH), and physical performance adjusting for sociodemographic variables,
      behavioral characteristics, body mass index, season, cognition, health
      conditions, creatinine, hemoglobin, and albumin. RESULTS: Approximately 28.8% of
      women and 13.6% of men had vitamin D levels indicative of deficiency (serum 25OHD
      < 25.0 nmol/L) and 74.9% of women and 51.0% of men had vitamin D levels
      indicative of vitamin D insufficiency (serum 25OHD < 50.0 nmol/L). Vitamin D
      levels were significantly associated with SPPB score in men (beta coefficient
      [standard error (SE)]: 0.38 [0.18], p =.04) and handgrip strength in men (2.44
      [0.84], p =.004) and women (1.33 [0.53], p =.01). Men and women with serum 25OHD
      < 25.0 nmol/L had significantly lower SPPB scores whereas those with serum 25OHD
      < 50 nmol/L had significantly lower handgrip strength than those with serum 25OHD
      > or =25 and > or =50 nmol/L, respectively (p <.05). PTH was significantly
      associated with handgrip strength only (p =.01). CONCLUSIONS: Vitamin D status
      was inversely associated with poor physical performance. Given the high
      prevalence of vitamin D deficiency in older populations, additional studies
      examining the association between vitamin D status and physical function are
      needed.

PMID- 17452743
TI  - Evaluation of oxidative stress and effectiveness of low-dose glucocorticoid
      therapy on exacerbation of chronic obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) and its exacerbation are
      considered to be related to oxidative stress. We determined the levels of
      reactive oxygen metabolites (ROM) and a biological antioxidant potential (BAP) in
      blood before and after the exacerbation. METHODS: For these determinations, the
      Free Radical Analytical System 4 was used. Twenty-one male patients were divided
      into two groups. RESULTS: Group A patients (n = 11, for whom the disease was end
      stage) showed high ROM levels and low BAP levels. Meanwhile, Group B patients (n
      = 10, for whom the disease was not end-stage but the exacerbation was repeated)
      exhibited variable ROM levels corresponding to the symptoms. Before the
      exacerbation, ROM levels increased. After administering high-dose
      glucocorticoids, the exacerbation disappeared and ROM levels decreased to the
      baseline. To suppress the relapse, the Group B patients were medicated with low
      dose glucocorticoids by inhalation and systemic administration. Then, ROM levels
      did not increase or the relapse did not occur. BAP levels continued to be low,
      and were restored after a stable state was obtained. CONCLUSION: Overproduction
      of ROM may precede exacerbation of COPD, and the low-dose glucocorticoid therapy
      may be effective to suppress its overproduction and to preserve COPD in a stable
      state.

PMID- 17452744
TI  - High cognitive dietary restraint is associated with increased cortisol excretion
      in postmenopausal women: a comment.

PMID- 17452746
TI  - SREBP-1 regulates the expression of heme oxygenase 1 and the phosphatidylinositol
      3 kinase regulatory subunit p55 gamma.
AB  - Sterol-regulatory element binding proteins (SREBPs) control the expression of
      genes involved in fatty acid and cholesterol biosynthesis. Using microarrays, we
      observed that mature SREBP-1 also induced the expression of genes unrelated to
      lipid metabolism, such as heme oxygenase 1 (HMOX1), plasma glutathione
      peroxidase, the phosphatidylinositol-3 kinase regulatory subunit p55 gamma,
      synaptic vesicle glycoprotein 2A, and COTE1. The expression of these genes was
      repressed upon addition of sterols, which block endogenous SREBP cleavage, and
      was induced by the statin drug mevinolin. Stimulation of fibroblasts with
      platelet-derived growth factor, which activates SREBP-1, had a similar effect.
      Fasted mice that were refed with a high-carbohydrate diet presented an increased
      expression of HMOX1 and p55 gamma in the liver. Overall, the transcriptional
      signature of SREBP-1 in fibroblasts stimulated by growth factors was very similar
      to that described in liver cells. We analyzed the HMOX1 promoter and found one
      SREBP binding site of the E-box type, which was required for regulation by SREBP
      1a and SREBP-1c but was insensitive to SREBP-2. In conclusion, our data suggest
      that SREBP-1 regulates the expression of stress response and signaling genes,
      which could contribute to the metabolic response to insulin and growth factors in
      various tissues.

PMID- 17452747
TI  - Cytoplasmic lipid droplet accumulation in developing mammary epithelial cells:
      roles of adipophilin and lipid metabolism.
AB  - PAT proteins (perilipin, adipophilin, and TIP47) are hypothesized to be critical
      regulators of lipid accumulation in eukaryotic cells. We investigated the
      developmental relationships between the expression of these proteins and
      cytoplasmic lipid droplet (CLD) accumulation in differentiating secretory
      epithelial cells in mouse mammary glands. Adipophilin (ADPH) specifically
      localized to CLD in differentiating and lactating mammary glands and was found
      exclusively in the secreted lipid droplet fraction of mouse milk. ADPH
      transcripts were selectively detected in secretory epithelial cells, and steady
      state levels of both ADPH mRNA and protein increased during secretory
      differentiation in patterns consistent with functional linkage to CLD
      accumulation. TIP47 also was detected in secretory epithelial cells; however, it
      had a diffuse punctate appearance, and its mRNA and protein expression patterns
      did not correlate with CLD accumulation. Perilipin-positive adipose cells and
      steady-state levels of perilipin mRNA and protein decreased during mammary gland
      differentiation, suggesting a progressive loss of adipose lipid storage during
      this process. Collectively, these data demonstrate that increased ADPH expression
      is a specialized property of differentiated secretory epithelial cells and
      provide developmental evidence specifically linking increased ADPH expression to
      increased CLD accumulation. In addition, evidence is presented that the
      epithelial and adipose compartments of the mammary gland undergo concerted,
      developmentally regulated shifts in lipid metabolism that increase the
      availability of fatty acids necessary for lipid synthesis by milk-secreting
      cells.

PMID- 17452748
TI  - Ethylene-sensitive and insensitive regulation of transcription factor expression
      during in vitro tomato sepal ripening.
AB  - Tomato (Solanum lycopersicum, formerly Lycopersicon esculentum) cv. VFNT Cherry
      sepals, when cultured in vitro between 16 degrees C and 22 degrees C, change
      their genetic programme to that of ripening fruit. Previously regulation of a
      number of transcription factors and a putative G-protein-coupled receptor that
      may be involved in tomato fruit ripening and cool-temperature sepal morphogenesis
      had been revealed. Many of those genes such as TAG1, TM4, TM6, AP2-like
      (LeAP2FR), YABBY2-like (LeYAB2), and LeCOR413-PM1 have not been investigated for
      ethylene regulation. Ethylene-independent, regulated transcripts may be part of
      an early signalling process induced or de-repressed by cool temperature that
      causes a switch in the genetic programme of the sepals. In this paper, ethylene
      regulation of a number of these and other putative signalling factors are
      investigated during cool-temperature-induced sepal morphogenesis. 1
      Methylcyclopropene was used to block ethylene-induced gene expression by
      interrupting the ethylene signal transduction pathway that occurs in ripening
      tomato fruits and presumably in ripening sepals. Transcripts of several putative
      transcription factors previously shown to be up-regulated during cool-temperature
      induced sepal morphogenesis (TAG1, TM4, LeAP2FR) were only slightly or not
      induced in 1-methylcyclopropene-treated sepals, indicating either direct or
      indirect ethylene regulation. Two genes, VAHOX1, a homeobox domain leucine-zipper
      encoding gene, and LeYAB2, a putative zinc-finger transcription factor-encoding
      gene, increased in treated and untreated sepals indicating regulation by cool
      temperatures independently of ethylene.

PMID- 17452749
TI  - Medicago truncatula ENOD40-1 and ENOD40-2 are both involved in nodule initiation
      and bacteroid development.
AB  - The establishment of a nitrogen-fixing root nodule on legumes requires the
      induction of mitotic activity of cortical cells leading to the formation of the
      nodule primordium and the infection process by which the bacteria enter this
      primordium. Several genes are up-regulated during these processes, among them
      ENOD40. Here it is shown, by using gene-specific knock-down of the two Medicago
      truncatula ENOD40 genes, that both genes are involved in nodule initiation.
      Further, during nodule development, both genes are essential for bacteroid
      development.

PMID- 17452750
TI  - Role of DNA endoreduplication, lipotubuloids, and gibberellic acid in epidermal
      cell growth during fruit development of Ornithogalum umbellatum.
AB  - Cytophotometry of individual nuclei was used to examine the level of
      endoreduplication in epidermal cells from the upper and lower parts of the ovary
      during Ornithogalum umbellatum flower and fruit development. An increase in DNA
      content from 2-4C to 2-8C in both parts of the ovary was observed, while the
      epidermal cell surface area grew about 6-fold and 15-fold in the lower and upper
      parts of the ovary, respectively. However, the correlation between mean epidermal
      cell size and ploidy was distinct during epidermis growth. Lipotubuloids became
      bigger in the upper than in the lower part during ovary and fruit development. In
      addition, more dynamic growth of the epidermal cells of the upper than of the
      lower part of the ovary was connected to the higher content of gibberellic acid.
      A hypothesis has been put forward that the role of DNA endoreduplication in
      epidermal cell growth was modulated by the function of lipotubuloids and the
      gradient of gibberellin.

PMID- 17452751
TI  - Characterization of a cinnamoyl-CoA reductase that is associated with stem
      development in wheat.
AB  - Cinnamoyl-CoA reductase (CCR) is responsible for the CoA ester to aldehyde
      conversion in monolignol biosynthesis, which diverts phenylpropanoid-derived
      metabolites into the biosynthesis of lignin. To gain a better understanding of
      lignin biosynthesis and its biological function, a cDNA encoding CCR was
      identified from wheat (Triticum aestivum L.), and designated as Ta-CCR1.
      Phylogenetic analysis indicated that Ta-CCR1 grouped together with other monocot
      CCR sequences while it diverged from Ta-CCR2. DNA gel-blot and mapping analyses
      demonstrated that Ta-CCR1 is present as a single copy gene in the wheat genome.
      Recombinant Ta-CCR1 protein converted feruloyl CoA, 5-OH-feruloyl CoA, sinapoyl
      CoA, and caffeoyl CoA, but feruloyl-CoA was the best substrate, suggesting the
      preferential biosynthesis of G-type lignin. RNA gel-blot analysis indicated that
      Ta-CCR1 was highly expressed in stem, with lower expression in leaves, and
      undetectable expression in roots. CCR enzyme activity was increased progressively
      along with the lignin biosynthesis and stem maturity. During stem development, Ta
      CCR1 mRNA levels remained high at elongation, heading, and milky stages in the
      wheat H4564 cultivar, while they declined dramatically at the heading and milky
      stages in stems of the C6001 cultivar. Ta-CCR1 mRNA expression paralleled
      extractable CCR enzyme activity in these two cultivars. Furthermore, high Ta-CCR1
      mRNA levels and high CCR enzyme activity in wheat stem were correlated with a
      higher Klason lignin content and greater stem mechanical strength in the H4564
      cultivar. This suggests that Ta-CCR1 and its related CCR enzyme may be involved
      in the regulation of lignin biosynthesis during stem maturity and then
      contributes to stem strength support in wheat.

PMID- 17452752
TI  - Isolation, functional characterization, and expression analysis of grapevine
      (Vitis vinifera L.) hexose transporters: differential roles in sink and source
      tissues.
AB  - Three hexose transporters (VvHT3, VvHT4, and VvHT5) were cloned from Vitis
      vinifera L. and functionally characterized in the hexose transport-impaired
      Saccharomyces cerevisiae mutant EBY.VW4000. Both VvHT4 and VvHT5 facilitated
      glucose uptake, with K(m)s of 137 muM and 89 muM, respectively. VvHT3 was not
      functional in the yeast system but a VvHT3:GFP (green fluorescent protein) fusion
      protein was targeted to the plasma membrane in plant cells. In young 'sink'
      leaves, transcript levels of all five VvHTs and a cell wall invertase (VvcwINV)
      were low. In mature leaves, there were increased levels of VvHT1, VvHT3, VvHT5,
      and VvcwINV transcripts, suggesting that mature leaves may have an increased
      capacity for apoplastic sucrose hydrolysis and hexose retrieval. In grape
      berries, VvHT1, VvHT2, and VvHT3 transcript levels were found to be significantly
      higher than those of VvHT4 and VvHT5. VvHT1 was most highly expressed early in
      berry development but decreased during the period of rapid sugar accumulation,
      while VvHT2 and VvHT3 expression remained high during this accumulation phase.
      VvcwINV expression occurred throughout berry development but peaked just prior to
      veraison. It is clear that the machinery to transport the hexose molecules
      produced through the cleavage of sucrose, by cell wall invertase, is present in
      the berry. This agrees with the suggestion that hexose accumulation to high
      levels during the ripening phase occurs through an apoplastic pathway.
      Interestingly, there is no direct relationship between VvHT gene expression and
      hexose accumulation, which suggests either that transcription is not the main
      determinant of transport activity or that other transport pathways are also
      active.

PMID- 17452753
TI  - Salt tolerance, salt accumulation, and ionic homeostasis in an epidermal bladder
      cell-less mutant of the common ice plant Mesembryanthemum crystallinum.
AB  - The aerial surfaces of the common or crystalline ice plant Mesembryanthemum
      crystallinum L., a halophytic, facultative crassulacean acid metabolism species,
      are covered with specialized trichome cells called epidermal bladder cells
      (EBCs). EBCs are thought to serve as a peripheral salinity and/or water storage
      organ to improve survival under high salinity or water deficit stress conditions.
      However, the exact contribution of EBCs to salt tolerance in the ice plant
      remains poorly understood. An M. crystallinum mutant lacking EBCs was isolated
      from plant collections mutagenized by fast neutron irradiation. Light and
      electron microscopy revealed that mutant plants lacked EBCs on all surfaces of
      leaves and stems. Dry weight gain of aerial parts of the mutant was almost half
      that of wild-type plants after 3 weeks of growth at 400 mM NaCl. The EBC mutant
      also showed reduced leaf succulence and leaf and stem water contents compared
      with wild-type plants. Aerial tissues of wild-type plants had approximately 1.5
      fold higher Na(+) and Cl(-) content than the mutant grown under 400 mM NaCl for 2
      weeks. Na(+) and Cl(-) partitioning into EBCs of wild-type plants resulted in
      lower concentrations of these ions in photosynthetically active leaf tissues than
      in leaves of the EBC-less mutant, particularly under conditions of high salt
      stress. Potassium, nitrate, and phosphate ion content decreased with
      incorporation of NaCl into tissues in both the wild type and the mutant, but the
      ratios of Na(+)/K(+) and Cl(-)/NO(3)(-)content were maintained only in the leaf
      and stem tissues of wild-type plants. The EBC mutant showed significant
      impairment in plant productivity under salt stress as evaluated by seed pod and
      seed number and average seed weight. These results clearly show that EBCs
      contribute to succulence by serving as a water storage reservoir and to salt
      tolerance by maintaining ion sequestration and homeostasis within
      photosynthetically active tissues of M. crystallinum.

PMID- 17452754
TI  - Protection mechanisms in the resurrection plant Xerophyta viscosa (Baker): both
      sucrose and raffinose family oligosaccharides (RFOs) accumulate in leaves in
      response to water deficit.
AB  - Changes in water-soluble carbohydrates were examined in the leaves of the
      resurrection plant Xerophyta viscosa under conditions of water deficit. Sucrose
      and raffinose family oligosaccharides (RFOs), particularly raffinose, increased
      under these conditions, with the highest concentrations evident at 5% relative
      water content [RWC; 23.5 mg g(-1) dry weight (DW) and 17.7 mg g(-1) DW,
      respectively]. Importantly, these effects were reversible, with concentrations
      returning to levels comparable with that of the full turgor state 7 d after water
      deficit conditions were alleviated, providing evidence that both sucrose and RFOs
      may play a protective role in desiccated leaf tissue of X. viscosa. Further,
      because the sucrose-to-raffinose mass ratio of 1.3:1 observed in the dehydrated
      state was very low, compared with published data for other resurrection plants
      (always >5), it is suggested that, in X. viscosa leaves, RFOs serve the dual
      purpose of stress protection and carbon storage. XvGolS, a gene encoding a
      galactinol synthase enzyme responsible for the first catalytic step in RFO
      biosynthesis, was cloned and functionally expressed. In leaf tissue exposed to
      water deficit, XvGolS transcript levels were shown to increase at 19% RWC. GolS
      activity in planta could not be correlated with RFO accumulation, but a negative
      correlation was observed between RFO accumulation and myo-inositol depletion,
      during water deficit stress. This correlation was reversed after rehydration,
      suggesting that during water deficit myo-inositol is channelled into RFO
      synthesis, but during the rehydration process it is channelled to metabolic
      pathways related to the repair of desiccation-induced damage.

PMID- 17452755
TI  - Loss of anthocyanins in red-wine grape under high temperature.
AB  - To determine the mechanism of inhibition of anthocyanin accumulation in the skin
      of grape berries due to high temperature, the effects of high temperature on
      anthocyanin composition and the responses in terms of gene transcript levels were
      examined using Vitis vinifera L. cv. Cabernet Sauvignon. High temperature
      (maximum 35 degrees C) reduced the total anthocyanin content to less than half of
      that in the control berries (maximum 25 degrees C). HPLC analysis showed that the
      concentrations of anthocyanins, with the exception of malvidin derivatives (3
      glucoside, 3-acetylglucoside, and 3-p-coumaroylglucoside), decreased considerably
      in the berries grown under high temperature as compared with the control.
      However, Affymetrix Vitis GeneChip microarray analysis indicated that the
      anthocyanin biosynthetic genes were not strongly down-regulated at high
      temperature. A quantitative real time PCR analysis confirmed this finding. To
      demonstrate the possibility that high temperature increases anthocyanin
      degradation in grape skin, stable isotope-labelled tracer experiments were
      carried out. Softened green berries of Cabernet Sauvignon were cut and
      aseptically incubated on filter paper with 1 mM aqueous L-[1-(13)C]phenylalanine
      solution for 1 week. Thereafter, the changes in (13)C-labelled anthocyanins were
      examined under different temperatures (15, 25, and 35 degrees C). In the berries
      cultured at 35 degrees C, the content of total (13)C-labelled anthocyanins that
      were produced before exposure to high temperature was markedly reduced as
      compared with those cultured at 15 degrees C and 25 degrees C. These data suggest
      that the decrease in anthocyanin accumulation under high temperature results from
      factors such as anthocyanin degradation as well as the inhibition of mRNA
      transcription of the anthocyanin biosynthetic genes.

PMID- 17452756
TI  - Class prediction of closely related plant varieties using gene expression
      profiling.
AB  - In recent years, class prediction experiments have been largely developed in
      cancer research with the aim of classifying unknown samples by examining their
      expression signature. In natural populations, a significant component of gene
      expression variability is also heritable. Citrus species are an ideal model to
      accomplish the study of these questions in plants, due to the existence of
      varieties derived from somatic mutations that are likely to differ from each
      other by one or a few point mutations but are phenotypically indistinguishable at
      early vegetative stages. The small genetic variability existing among these
      varieties makes molecular markers ineffective in distinguishing genotypes within
      a particular species. Gene expression profiles have been used to predict mandarin
      clementine varieties (Citrus clementina Hort. ex Tan.) by means of two
      independent supervised learning algorithms: Support Vector Machines and
      Prediction Analysis of Microarrays. The results show that transcriptional
      variation is variety-dependent in citrus, and supervised clustering methods may
      correctly assign blind samples to varieties when both training and test samples
      are under the same experimental conditions.

PMID- 17452757
TI  - Physiological relationships among physical, sensory, and morphological attributes
      of texture in tomato fruits.
AB  - Tomato texture is one of the critical components for the consumer's perception of
      fruit quality. Texture is a complex character composed of several attributes that
      are difficult to evaluate and which change during fruit ripening. This study
      investigated the texture of tomato fruits at the rheological, sensory,
      morphological, and genetic levels, and attempted to correlate several parameters.
      Analyses were performed on tomato fruits from introgressed lines carrying
      quantitative trait loci (QTLs) associated with texture traits localized on
      different chromosomes, in two genetic backgrounds. Rheological measurements were
      used to determine resistance to deformation and fruit elasticity. Sensory
      analysis was used to assess flesh firmness, juiciness, mealiness, and skin
      toughness. Image analysis was used to study fruit morphology and to define the
      cellular structure and heterogeneity of the pericarp. A highly significant
      correlation was observed between instrumental and sensory firmness. Moreover,
      correlations were also established between some texture traits and parameters of
      the pericarp cellular structure. Compared with QTLs detected in a previous study,
      the phenotypic effects expected for mealiness were confirmed in all lines,
      whereas, for firmness, they were not confirmed. Significant interactions between
      QTL and genetic background were observed for several traits. In addition, kinetic
      analysis showed that differences in firmness occurred from the early stages of
      fruit development. These results provide both a broad description of texture
      components and preliminary information to understand their genetic control.

PMID- 17452759
TI  - Independent medical research.

PMID- 17452760
TI  - Causes and consequences of a non-dipping blood pressure profile.
AB  - The development and clinical application of ambulatory blood pressure monitoring
      (ABP M) has brought several of the main features of the circadian blood pressure
      (BP) rhythm to light. ABP M has shown to be a very useful method in
      cardiovascular risk assessment and remains the only method of diagnosing a non
      dipping blood pressure profile. A 'non-dipping' BP profile is currently regarded
      as a risk factor in its own right for cardiovascular (CV) events and target organ
      damage. Nevertheless, the reliability of ABP M in assessing dipping status is
      still being questioned. Furthermore, a clear-cut definition of 'non-dipping' has
      not been established so far. The pathophysiological mechanism(s) of a non-dipping
      profile might involve abnormalities in extracellular volume and/or vascular
      resistance regulation. In addition, differences in daytime and nighttime
      activity, sleep quality and body position during sleep are involved as well. A
      reduction in cardiovascular risk by a pharmacologically induced switch from a non
      dipper to a dipper status might be expected, but remains to be proven.

PMID- 17452761
TI  - Ewing's sarcoma and primitive neuroectodermal tumour in adults: single-centre
      experience in The Netherlands.
AB  - BACKGROUND: Ewing's sarcoma and peripheral primitive neuroectodermal tumours
      (PNET) are rare tumours and closely related. They occur most often in children
      and adolescents. Few studies have been published on treatment outcome in adult
      patients. METHODS: We performed a retrospective analysis of patients aged >16
      years who were primarily treated at our university hospital for Ewing's sarcoma
      or PNET. In general, treatment consisted of long-term multiagent chemotherapy,
      interrupted by individualised local treatment consisting of surgery and/or
      radiotherapy. We reviewed clinical features and outcomes to present our
      experience with Ewing's sarcoma and PNET in adults. RESULTS: From 1979 to 2002,
      27 patients with Ewing's sarcoma (20) or PNET (7) were treated. There were 22 men
      and 5 women, with a median age of 25 years (range 17-49). Ten patients presented
      with metastases predominantly in lungs (4) or bones (6). Combination therapy
      consisted of chemotherapy (27), surgery (16) and radiotherapy (16). After a
      median follow-up of ten years, 14 patients have died (toxicity = 2, progressive
      disease = 12) and 13 patients are alive and free of disease. Five-year overall
      survival was 58%. All four patients with bone metastases died, while all five
      patients presenting with lung metastases are disease-free. CONCLUSION: The five
      year overall survival of 58% in this small series on adult patients is in line
      with paediatric study outcomes. Patients with lung metastases may even be cured
      by multimodality therapy. We therefore strongly advocate referral of patients
      with this rare disease to a specialised oncology centre.

PMID- 17452762
TI  - Cushing's syndrome and bone mineral density: lowest Z scores in young patients.
AB  - BACKGROUND: Patients with Cushing's syndrome have a high prevalence of
      osteoporotic fractures. Little is known about factors determining bone mineral
      density (BMD) in these patients. OBJECTIVE: To evaluate which factors influence
      BMD at the time of diagnosis of Cushing's syndrome. METHODS: In 77 consecutive
      patients with Cushing's syndrome with a median age of 41.1 (interquartile range
      31.1 to 52.2) years we measured BMD of the lumbar spine and the femoral neck at
      the time of diagnosis. From the medical records we obtained information on
      possible predictors of BMD. We compared BMD with a reference population by means
      of the Z score. Adjustment for other variables than age and sex was made with
      linear regression models. RESULTS: Patients with Cushing's syndrome had a low Z
      score in both the lumbar spine (-1.07 SD (95% CI -1.43 to -0.71 SD )) and in the
      femoral neck (-0.81 SD (95% CI -1.06 to -0.55 SD )). 82% of patients had
      osteopenia at one or both sites (T score lower than -1 SD ), including 31% with
      osteoporosis (T score -2.5 SD or lower). The main determinant of the Z score at
      both sites and for both sexes was age. Z score increased by about 0.4 SD per
      decade. 81% of patients.

PMID- 17452763
TI  - Coma with ECG abnormalities: consider tricyclic antidepressant intoxication.
AB  - Two comatose patients with a psychiatric history were admitted to our hospital.
      On admission both presented with major cardiovascular instability and needed
      urgent intensive care treatment. Although initially not suspected, the coma was
      caused by tricyclic antidepressant intoxication (TCA). Serious neurological,
      anticholinergic and cardiovascular effects may occur in TCA intoxication. In any
      comatose patient with ECG changes and a psychiatric history, TCA intoxication
      should be strongly suspected.

PMID- 17452764
TI  - Successful management of chronic myeloid leukaemia with leucapheresis during a
      twin pregnancy.
AB  - We present a 36-year-old woman in whom chronic myeloid leukaemia (CML) was
      diagnosed during a twin pregnancy. Because of hyperleucocytosis, we started
      leucapheresis also with the goal of gaining time for discussing treatment
      options. As this strategy was so effective and our patient was reluctant to take
      medication, we decided to continue this treatment.

PMID- 17452765
TI  - A woman with Cushing's syndrome after use of an Indonesian herb: a case report.
AB  - A 69-year-old woman developed Cushing's syndrome after long-term use of Sinatren,
      an Indonesian over the-counter drug, which was pharmacologically analysed three
      times before the correct content was discovered. After discontinuation she
      developed adrenal insufficiency, for which she needed substitution of steroids.
      Physicians should be aware of the presence of corticosteroids in over-the-counter
      products, that are not mentioned on the instruction leaflet.

PMID- 17452766
TI  - Photo quiz. Sine waves.

PMID- 17452767
TI  - Extensive jejunal diverticulosis in a family, a matter of inheritance?
AB  - Diverticulosis of the jejunum is a rare finding (0.06 to 1.3%). Possible
      complications are bacterial overgrowth, malabsorption, bleeding, mechanical
      obstruction, volvulus and perforation. At present only one case report on
      familial jejunal diverticulosis has been published. We describe three patients
      with jejunal diverticulosis within one family, which might suggest inheritance.

PMID- 17452769
TI  - The 13th Fanconi anemia gene identified: FANCI--importance of the 'Fanconi anemia
      pathway' for cellular oncology.

PMID- 17452770
TI  - The molecular basis of retinoids' use in breast cancer chemoprevention.

PMID- 17452771
TI  - Population screening for colorectal cancer: faeces, endoscopes or X-rays?
AB  - Colorectal carcinoma (CRC) is a common cancer and the second most common cause of
      death. The therapeutic costs for this disease will continue to rise due to an
      increasing incidence and the introduction of new chemotherapeutic modalities.
      Colorectal carcinoma is preceded by precursor lesions, which can be used as a
      target for early detection and therapy. Biennial population screening with faecal
      occult blood tests (FOBT) lowers CRC mortality with 14-18%. Five year screening
      with flexible sigmoidoscopy is a cost-effective alternative, which yields a
      higher preventive effect when similar participation rates are achieved. Screening
      colonoscopy has the advantage of examination of the complete colon but
      disadvantages are the high participant burden and the higher demand for
      endoscopic personnel and endoscopy units. Future screening modalities like faecal
      DNA markers and CT colonography are promising but need further improvement. In
      Europe, faecal occult blood testing and flexible sigmoidoscopy are currently the
      most suitable screening modalities for colorectal cancer screening.

PMID- 17452772
TI  - Emerging concepts of apolipoprotein D with possible implications for breast
      cancer.
AB  - Apolipoprotein D (ApoD) is a small glycoprotein of 24 kD, and a member of the
      lipocalin family. ApoD exerts several intracellular mechanistic roles, especially
      ligand binding. Some putative ligands are arachidonic acid, progesterone, and
      tamoxifen. It probably has a binding/reservoir function of these ligands in the
      cytoplasm. Furthermore, ApoD has features compatible with endosomal trafficking,
      proteolytic activity and interactions in cellular signal pathways. ApoD inhibits
      translocation of phosphorylated MAPK into the nucleus. Moreover, ApoD is
      associated with reduced proliferative activity of cancer cells, and is abundantly
      raised in senescent cells. In breast cancer, ApoD expression is associated with
      favourable histology and clinical stage, whereas in adjacent tumour stroma ApoD
      expression is a marker of adverse prognosis. Oestrogen receptor expression in
      breast cancer is inversely related to ApoD expression. Therefore, a combined
      oestrogen receptor positivity/ApoD positivity, could reflect a non-functional
      oestrogen receptor pathway, and this subset of breast cancer patients does not
      react to adjuvant tamoxifen treatment. The triangular relationship between
      oestrogen receptor, tamoxifen and ApoD should be further explored.

PMID- 17452773
TI  - Identification of the Fanconi anemia complementation group I gene, FANCI.
AB  - To identify the gene underlying Fanconi anemia (FA) complementation group I we
      studied informative FA-I families by a genome-wide linkage analysis, which
      resulted in 4 candidate regions together encompassing 351 genes. Candidates were
      selected via bioinformatics and data mining on the basis of their resemblance to
      other FA genes/proteins acting in the FA pathway, such as: degree of evolutionary
      conservation, presence of nuclear localization signals and pattern of tissue
      dependent expression. We found a candidate, KIAA1794 on chromosome 15q25-26, to
      be mutated in 8 affected individuals previously assigned to complementation group
      I. Western blots of endogenous FANCI indicated that functionally active KIAA1794
      protein is lacking in FA-I individuals. Knock-down of KIAA1794 expression by
      siRNA in HeLa cells caused excessive chromosomal breakage induced by mitomycin C,
      a hallmark of FA cells. Furthermore, phenotypic reversion of a patient-derived
      cell line was associated with a secondary genetic alteration at the KIAA1794
      locus. These data add up to two conclusions. First, KIAA1794 is a FA gene.
      Second, this gene is identical to FANCI, since the patient cell lines found
      mutated in this study included the reference cell line for group I, EUFA592.

PMID- 17452774
TI  - Hypoxia and angiogenesis in endometrioid endometrial carcinogenesis.
AB  - BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1alpha) plays an essential role
      in the adaptive response of cells to hypoxia, triggering biologic events
      associated with aggressive tumor behavior. METHODS: Expression of HIF-1alpha and
      proteins in the HIF-1alpha pathway (Glut-1, CAIX, VEGF) in paraffin-embedded
      specimens of normal (n=17), premalignant (n=17) and endometrioid endometrial
      carcinoma (n=39) was explored by immunohistochemistry, in relation to microvessel
      density (MVD). RESULTS: HIF-1alpha overexpression was absent in inactive
      endometrium but present in hyperplasia (61%) and carcinoma (87%), with increasing
      expression in a perinecrotic fashion pointing to underlying hypoxia. No
      membranous expression of Glut-1 and CAIX was noticed in inactive endometrium, in
      contrast with expression in hyperplasia (Glut-1 0%, CAIX 61%, only focal and
      diffuse) and carcinoma (Glut-1 94.6%, CAIX 92%, both mostly perinecrotically).
      Diffuse HIF-1alpha was accompanied by activation of downstream targets. VEGF was
      significantly higher expressed in hyperplasias and carcinomas compared to
      inactive endometrium. MVD was higher in hyperplasias and carcinomas than in
      normal endometrium (p<0.001). CONCLUSION: HIF-1alpha and its downstream genes are
      increasingly expressed from normal through premalignant to endometrioid
      adenocarcinoma of the endometrium, paralleled by activation of its downstream
      genes and increased angiogenesis. This underlines the potential importance of
      hypoxia and its key regulator HIF-1alpha in endometrial carcinogenesis.

PMID- 17452775
TI  - Stromal expression of hypoxia regulated proteins is an adverse prognostic factor
      in colorectal carcinomas.
AB  - BACKGROUND: Hypoxia modifies the phenotype of tumors in a way that promotes tumor
      aggressiveness and resistance towards chemotherapy and radiotherapy. However, the
      expression and influence of hypoxia-regulated proteins on tumor biology are not
      well characterized in colorectal tumors. We studied the role of protein
      expression of hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, carbonic
      anhydrase 9 (CA9) and glucose transporter 1 (GLUT1) in patients with colorectal
      adenocarcinomas. METHODS: Expression of HIF-1alpha, HIF-2alpha, CA9 and GLUT1 was
      quantified by immunohistochemistry in 133 colorectal adenocarcinomas. The
      expression of hypoxia markers was correlated with clinicopathological variables
      and overall patient survival. RESULTS: Expression of these hypoxia markers was
      detected in the epithelial compartment of the tumor cells as well as in tumor
      associated stromal cells. Although tumor cells frequently showed expression of
      one or more of the investigated hypoxia markers, no correlation among these
      markers or with clinical response was found. However, within the tumor stroma,
      positive correlations between the hypoxia markers HIF-2alpha, CA9 and GLUT1 were
      observed. Furthermore expression of HIF-2alpha and CA9 in tumor-associated stroma
      were both associated with a significantly reduced overall survival. In the Cox
      proportional hazard model, stromal HIF-2alpha expression was an independent
      prognostic factor for survival. CONCLUSION: These observations show, that
      expression of hypoxia regulated proteins in tumor-associated stromal cells, as
      opposed to their expression in epithelial tumor cells, is associated with poor
      outcome in colorectal cancer. This study suggests that tumor hypoxia may
      influence tumor-associated stromal cells in a way that ultimately contributes to
      patient prognosis.

PMID- 17452776
TI  - 655Val and 1170Pro ERBB2 SNPs in familial breast cancer risk and BRCA1
      alterations.
AB  - Human ERBB2 presents several SNPs. One of these, Ile655Val, introduces a
      structural change in the transmembrane region of ERBB2 and has been the focus of
      debate over its potential role as a susceptibility marker for breast cancer risk.
      Another SNP, Ala1170Pro, introduces a structural change in the carboxyl-terminal
      regulatory domain of the protein, but its clinical and biological importance
      remains undefined. The aim of this study was to investigate the association of
      rare alleles of both SNPs and the risk of developing breast cancer, BRCA1
      alterations and clinical-pathological features of Caucasian breast cancer
      patients with familial history of breast/ovarian cancer. The originality of the
      present paper is that it is the only specifically focusing on the relationship
      between ERBB2 SNPs and familiarity/BRCA1 characteristics. A consecutive series of
      628 patients with first diagnosis of breast cancer and 169 healthy people had DNA
      analyzed for both SNPs. Genotypic or allelic frequencies of ERBB2 SNPs in breast
      cancer patients were similar than in controls. The variant allele 655Val was
      significantly associated with younger age (p=0.009) particularly associated with
      patient family history of breast cancer (p=0.02). The 655Val allele was also more
      commonly found in invasive, while the variant 1170Pro in estrogen receptor
      positive breast cancers. Furthermore, this last SNP seems to be strictly
      associated with the presence of BRCA1 polymorphisms. In conclusion, these
      findings point to the existence of an association of ERBB2 allelic variants at
      both loci with specific breast tumor phenotypes and to the need of deeply
      investigate different gene SNPs association for risk defining.

PMID- 17452777
TI  - TNFalpha-308G/A polymorphism as a risk factor for HPV associated cervical cancer
      in Indian population.
AB  - BACKGROUND: Investigation of the potential association of single nucleotide
      polymorphisms (SNPs) at -308 G/A and -238 G/A of Tumor necrosis factor alpha
      (TNFalpha) with susceptibility to HPV-16 associated cervical cancer in Indian
      women. METHODS: The study included 165 histologically confirmed cases with 45
      precancer and 120 cancer patients and an equal number (165) of healthy controls
      with normal cervical cytology. PCR-RFLP was employed to analyze TNFalpha promoter
      polymorphisms, which were confirmed by direct sequencing. Both patients and
      controls were screened for Human Papillomavirus (HPV) infection. RESULTS: The
      frequency of -308 A allele in TNFalpha was significantly higher in cases compared
      with control subjects (21% in cases vs. 9% in controls; p<0.01), with an odds
      ratio of 2.7 (95% CI = 1.41-5.15). Also, women carrying A allele for this locus
      presented 3 times increased susceptibility to HPV 16 infection as evident from
      carrier genotype distribution between HPV positive cases and control subjects
      (24% in HPV positive cases vs. 9% in controls; p<0.01; OR = 3.1; 95% CI = 1.60
      6.03). No such association was found for TNFalpha-238 (G/A) polymorphism with the
      risk of development of cervical cancer. CONCLUSION: It suggests that SNP at -308
      (G/A) of TNFalpha promoter may represent an increased risk for HPV infection and
      development of cervical cancer in Indian women.

PMID- 17452778
TI  - EGFR and K-ras mutation analysis in non-small cell lung cancer: comparison of
      paraffin embedded versus frozen specimens.
AB  - BACKGROUND: Mutational analysis of the Epidermal Growth Factor Receptor (EGFR)
      and K-ras genes to select non-small cell lung cancer (NSCLC) patients for
      treatment with novel EGFR tyrosine kinase inhibitors is an appealing possibility
      currently under investigation. Although frozen tumor tissue would probably be the
      optimal source for analysis, the most common source of tumor material is fixed
      and paraffin embedded (FPE) archival specimens. Here, we evaluate how different
      procedures of tissue sample processing and preservation may affect the outcome of
      EGFR and K-ras mutation analysis. Furthermore, we compare the sensitivity of the
      analysis using genomic DNA (gDNA) versus RNA. METHODS: We used PCR amplification
      and direct sequencing to analyze EGFR and K-ras genes in paired FPE and frozen
      tumor samples corresponding to 47 NSCLC patients. In frozen samples, the analysis
      was carried out using both gDNA and RNA extracted in parallel. RESULTS: Whereas
      100% of frozen samples were successfully amplified, the rate of successful PCR
      amplification in FPE samples was approximately 50%. We detected three previously
      described EGFR point mutations in 2 samples. In ten other samples, a K-ras
      mutation was observed. These mutations were detected in DNA extracted from frozen
      samples as well as in DNA obtained from FPE tissue. In addition, 10 nucleotide
      changes, were detected in FPE samples that were not detected in the frozen
      specimens. Upon re-analysis, these nucleotide changes could not be confirmed and
      were most likely the result of paraffin embedding and fixation procedures. All
      mutations found in gDNA were also detected in the corresponding RNA and, in two
      cases, the presence of the mutant allele was easier to identify by using RNA.
      CONCLUSIONS: Our results indicate that RNA extracted from frozen tissue is the
      preferred source for EGFR and K-ras mutation testing. When analyzing FPE samples,
      reducing the size of the amplified fragments would increase PCR success rate, and
      care should be taken to control for false-positive results.

PMID- 17452779
TI  - Silencing human Rb2/p130 with shRNA.

PMID- 17452780
TI  - Structure of the mexicain-E-64 complex and comparison with other cysteine
      proteases of the papain family.
AB  - Mexicain is a 23.8 kDa cysteine protease from the tropical plant Jacaratia
      mexicana. It is isolated as the most abundant product after cation-exchange
      chromatography of the mix of proteases extracted from the latex of the fruit. The
      purified enzyme inhibited with E-64 [N-(3-carboxyoxirane-2-carbonyl)-leucyl
      amino(4-guanido)butane] was crystallized by sitting-drop vapour diffusion and the
      structure was solved by molecular replacement at 2.1 A resolution and refined to
      an R factor of 17.7% (R(free) = 23.8%). The enzyme belongs to the alpha+beta
      class of proteins and the structure shows the typical papain-like fold composed
      of two domains, the alpha-helix-rich (L) domain and the beta-barrel-like (R)
      domain, separated by a groove containing the active site formed by residues Cys25
      and His159, one from each domain. The four monomers in the asymmetric unit show
      one E-64 molecule covalently bound to Cys25 in the active site and differences
      have been found in the placement of E-64 in each monomer.

PMID- 17452781
TI  - Heterogeneous nucleation of three-dimensional protein nanocrystals.
AB  - Nucleation is the rate-limiting step in protein crystallization. Introducing
      heterogeneous substrates may in some cases lower the energy barrier for
      nucleation and thereby facilitate crystal growth. To date, the mechanism of
      heterogeneous protein nucleation remains poorly understood. In this study, the
      nucleating properties of fragments of human hair in crystallization experiments
      have been investigated. The four proteins that were tested, lysozyme, glucose
      isomerase, a polysaccharide-specific Fab fragment and potato serine protease
      inhibitor, nucleated preferentially on the hair surface. Macrocrystals and
      showers of tiny crystals of a few hundred nanometres thickness were obtained also
      under conditions that did not produce crystals in the absence of the nucleating
      agent. Cryo-electron diffraction showed that the nanocrystals diffracted to at
      least 4 A resolution. The mechanism of heterogeneous nucleation was studied using
      confocal fluorescent microscopy which demonstrated that the protein is
      concentrated on the nucleating surface. A substantial accumulation of protein was
      observed on the sharp edges of the hair's cuticles, explaining the strong
      nucleating activity of the surface.

PMID- 17452782
TI  - Structures of vaccinia virus dUTPase and its nucleotide complexes.
AB  - Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) catalyzes the hydrolysis
      of dUTP to dUMP and pyrophosphate in the presence of Mg(2+) ions. The enzyme
      plays multiple cellular roles by maintaining a low dUTP:dTTP ratio and by
      synthesizing the substrate for thymidylate synthase in the biosynthesis of dTTP.
      Although dUTPase is an essential enzyme and has been established as a valid
      target for drug design, the high degree of homology of vaccinia virus dUTPase to
      the human enzyme makes the identification of selective inhibitors difficult. The
      crystal structure of vaccinia virus dUTPase has been solved and the active site
      has been mapped by crystallographic analysis of the apo enzyme and of complexes
      with the substrate-analog dUMPNPP, with the product dUMP and with dUDP, which
      acts as an inhibitor. Analyses of these structures reveal subtle differences
      between the viral and human enzymes. In particular, the much larger size of the
      central channel at the trimer interface suggests new possibilities for structure
      based drug design. Vaccinia virus is a prototype of the poxviruses.

PMID- 17452783
TI  - Structure of the equine arteritis virus nucleocapsid protein reveals a dimer
      dimer arrangement.
AB  - Equine arteritis virus (EAV) is an enveloped positive-sense RNA virus belonging
      to the Arteriviridae family, which also includes the porcine pathogen PRRSV and
      is genetically and structurally related to the coronaviruses. EAV is an important
      equine pathogen that has caused significant economic losses to the horse-breeding
      industry and has been difficult to control. The EAV virion consists of a genome
      containing nucleocapsid core made of nucleocapsid (N) protein surrounded by a
      lipid envelope containing several membrane proteins. Here, the crystal structure
      of the capsid-forming domain of the EAV N protein is presented at 2.0 A
      resolution. The dimeric N-protein structure is similar to the previously
      determined structure of the N protein from PRRSV, with most differences localized
      to the terminal helices and flexible loops. The N protein is organized as dimers
      of dimers in the crystal, which may reflect the arrangement of the protein in the
      viral nucleocapsid.

PMID- 17452784
TI  - Structure of a CBS-domain pair from the regulatory gamma1 subunit of human AMPK
      in complex with AMP and ZMP.
AB  - AMP-activated kinase (AMPK) is central to sensing energy status in eukaryotic
      cells via binding of AMP and ATP to CBS (cystathionine beta-synthase) domains in
      the regulatory gamma subunit. The structure of a CBS-domain pair from human AMPK
      gamma1 in complex with the physiological activator AMP and the pharmacological
      activator ZMP (AICAR) is presented.

PMID- 17452785
TI  - Interpretation of ensembles created by multiple iterative rebuilding of
      macromolecular models.
AB  - Automation of iterative model building, density modification and refinement in
      macromolecular crystallography has made it feasible to carry out this entire
      process multiple times. By using different random seeds in the process, a number
      of different models compatible with experimental data can be created. Sets of
      models were generated in this way using real data for ten protein structures from
      the Protein Data Bank and using synthetic data generated at various resolutions.
      Most of the heterogeneity among models produced in this way is in the side chains
      and loops on the protein surface. Possible interpretations of the variation among
      models created by repetitive rebuilding were investigated. Synthetic data were
      created in which a crystal structure was modelled as the average of a set of
      ;perfect' structures and the range of models obtained by rebuilding a single
      starting model was examined. The standard deviations of coordinates in models
      obtained by repetitive rebuilding at high resolution are small, while those
      obtained for the same synthetic crystal structure at low resolution are large, so
      that the diversity within a group of models cannot generally be a quantitative
      reflection of the actual structures in a crystal. Instead, the group of
      structures obtained by repetitive rebuilding reflects the precision of the
      models, and the standard deviation of coordinates of these structures is a lower
      bound estimate of the uncertainty in coordinates of the individual models.

PMID- 17452786
TI  - Stereochemical restraints revisited: how accurate are refinement targets and how
      much should protein structures be allowed to deviate from them?
AB  - The Protein Data Bank and Cambridge Structural Database were analyzed with the
      aim of verifying whether the restraints that are most commonly used for protein
      structure refinement are still appropriate 15 years after their introduction.
      From an analysis of selected main-chain parameters in well ordered fragments of
      ten highest resolution protein structures, it was concluded that some of the
      currently used geometrical target values should be adjusted somewhat (the C-N
      bond and the N-C(alpha)-C angle) or applied with less emphasis (peptide
      planarity). It was also found that the weighting of stereochemical information in
      medium-resolution refinements is often overemphasized at the cost of the
      experimental information in the diffraction data. A correctly set balance will be
      reflected in root-mean-square deviations from ideal bond lengths in the range
      0.015-0.020 A for structures refined to R factors of 0.15-0.20. At ultrahigh
      resolution, however, the diffraction terms should be allowed to dominate, with
      even higher acceptable deviations from idealized standards in the well defined
      fragments of the protein. It is postulated that modern refinement programs should
      accommodate variable restraint weights that are dependent on the occupancies and
      B factors of the atoms involved.

PMID- 17452787
TI  - Probing the oxygen-binding site of the human formylglycine-generating enzyme
      using halide ions.
AB  - The catalytic residue in sulfatases is a unique formylglycine that is post
      translationally generated by oxidation of a cysteine or serine precursor.
      Molecular oxygen oxidizes the cysteine precursor in eukaryotic sulfatases, a
      reaction that is catalysed by the formylglycine-generating enzyme FGE.
      Previously, FGE was crystallized in complex with a chloride ion which, based on
      its similar polarizability and hydrophobicity, indicates the site of molecular
      oxygen binding. Here, two structures of FGE in complex with bromide and iodide
      were determined in order to further delineate the volume and stereochemical
      restraints of the oxygen-binding site for potential reaction intermediates.
      Anomalous difference density maps unambiguously assigned the nature of the halide
      ions. Unexpectedly, data collected at a wavelength of 1.54 A from the iodide
      containing crystal and data collected at a wavelength of 0.8 A from a bromide
      containing crystal were sufficient for SIRAS phasing.

PMID- 17452788
TI  - A Rac1-GDP trimer complex binds zinc with tetrahedral and octahedral
      coordination, displacing magnesium.
AB  - The Rho family of small GTPases represent well characterized signaling molecules
      that regulate many cellular functions such as actin cytoskeletal arrangement and
      the cell cycle by acting as molecular switches. A Rac1-GDP-Zn complex has been
      crystallized in space group P3(2)21 and its crystal structure has been solved at
      1.9 A resolution. These trigonal crystals reveal the unexpected ability of Rac1
      to coordinate Zn atoms in a tetrahedral fashion by use of its biologically
      relevant switch I and switch II regions. Upon coordination of zinc, the switch I
      region is stabilized in the GDP-bound conformation and contributes to a Rac1
      trimer in the asymmetric unit. Zinc coordination causes switch II to adopt a
      novel conformation with a symmetry-related molecule. Additionally, zinc was found
      to displace magnesium from its octahedral coordination at switch I, although GDP
      binding remained stable. This structure represents the first reported Rac1-GDP-Zn
      complex, which further underscores the conformational flexibility and versatility
      of the small GTPase switch regions.

PMID- 17452789
TI  - Protein crystallization by surface entropy reduction: optimization of the SER
      strategy.
AB  - A strategy of rationally engineering protein surfaces with the aim of obtaining
      mutants that are distinctly more susceptible to crystallization than the wild
      type protein has previously been suggested. The strategy relies on replacing
      small clusters of two to three surface residues characterized by high
      conformational entropy with alanines. This surface entropy reduction (or SER)
      method has proven to be an effective salvage pathway for proteins that are
      difficult to crystallize. Here, a systematic comparison of the efficacy of using
      Ala, His, Ser, Thr and Tyr to replace high-entropy residues is reported. A total
      of 40 mutants were generated and screened using two different procedures. The
      results reaffirm that alanine is a particularly good choice for a replacement
      residue and identify tyrosines and threonines as additional candidates that have
      considerable potential to mediate crystal contacts. The propensity of these
      mutants to form crystals in alternative screens in which the normal
      crystallization reservoir solutions were replaced with 1.5 M NaCl was also
      examined. The results were impressive: more than half of the mutants yielded a
      larger number of crystals with salt as the reservoir solution. This method
      greatly increased the variety of conditions that yielded crystals. Taken
      together, these results suggest a powerful crystallization strategy that combines
      surface engineering with efficient screening using standard and alternate
      reservoir solutions.

PMID- 17452790
TI  - Crystallization by capillary counter-diffusion and structure determination of the
      N114A mutant of the SH3 domain of Abl tyrosine kinase complexed with a high
      affinity peptide ligand.
AB  - The recognition of proline-rich ligands by SH3 domains is part of the process
      leading to diseases such as cancer or AIDS. Understanding the molecular
      determinants of the binding affinity and specificity of these interactions is
      crucial for the development of potent inhibitors with therapeutic potential. In
      this study, the crystallographic structure of the N114A mutant of the SH3 domain
      of the Abelson leukaemia virus tyrosine kinase complexed with a high-affinity
      peptide is presented. The crystallization was carried out using the capillary
      counter-diffusion technique, which facilitates the screening, manipulation and
      transport of the crystals and allows the collection of X-ray data directly from
      the capillary in which the crystals were grown. The crystals of the N114A mutant
      belong to the orthorhombic P2(1)2(1)2(1) space group, with unit-cell parameters a
      = 48.2, b = 50.1, c = 56.4 A. The quality of the diffraction data set has allowed
      the structure of the complex to be determined at a resolution limit of 1.75 A.

PMID- 17452791
TI  - High-pressure cryocooling for capillary sample cryoprotection and diffraction
      phasing at long wavelengths.
AB  - Crystal cryocooling is usually employed to reduce radiation damage during X-ray
      crystallography. Recently, a high-pressure cryocooling method has been developed
      which results in excellent diffraction-quality crystals without the use of
      penetrative cryoprotectants. Three new developments of the method are presented
      here: (i) Xe-He high-pressure cryocooling for Xe SAD phasing, (ii) native sulfur
      SAD phasing and (iii) successful cryopreservation of crystals in thick-walled
      capillaries without additional cryoprotectants other than the native mother
      liquor. These developments may be useful for structural solution of proteins
      without the need for selenomethionine incorporation and for high-throughput
      protein crystallography.

PMID- 17452792
TI  - Notes of a protein crystallographer: quo vadis structural biology?

PMID- 17452793
TI  - [The progress in research on the reduced nicotinamide adenine di(tri)-nucleotide
      phosophate [NAD(P)H] dehydrogenase complex and chlororespiration].
AB  - Besides the non-cyclic electron transport driven by the two photosystems (PSII
      and PSI), the cyclic electron transport pathways around PSI are also essential
      for efficient photosynthesis. As one of these pathways, the NAD(P)H dehydrogenase
      complex (NDH complex) mediated cyclic electron transport has been well studied.
      Along with the identification of the plastid terminal oxydase (PTOX), the
      functions of NDH-mediated cyclic and chlororepiratory electron transport in
      energy supply for photosynthesis as well as in the resistance to photooxidative
      stress have increasingly been brought to the researchers' attention. In the
      present paper, the structural characteristics of NDH complex, the regulatory
      mechanism, and the physiological significance of NDH mediated cyclic electron
      transport and chlororespiration are reviewed.

PMID- 17452794
TI  - [Application of selective microelectrode in plant physiological research].
AB  - Selective microelectrode technique, known as an electrophysiological approach,
      can be used to measure directly specific information on ion or molecule
      distribution and movement both inside and outside of living organelle, biological
      cells, tissue and organs. It has several advantages over other methods in
      measuring ionic or molecular information, e.g. easy to handle, fast response,
      high sensitivity (10(-12) moles cm(-2) s(-1)) and non-invasive to the samples in
      addition to continuous measurement and automatic monitoring. Microscopic-scale
      selective electrode (with a tip diameter of 0.5-5 microm) can be used to measure
      net fluxes of ions or molecules outside of growing biological cells, tissues and
      organs, to measure activities of ions or molecules inside of growing organelle
      and biological cells. Thus, it has many applications in various research fields.
      The technical principle of design and use of selective microelectrode and its
      progress and development prospect in plant physiological research are summarized.

PMID- 17452795
TI  - Salt and drought tolerance of transgenic salvia miltiorrhiza Bunge with the
      TaLEA1 gene.
AB  - TaLEA1, a gene encoding a late-embryogenesis-abundant protein, was cloned from
      wheat and was transformed into Salvia Miltiorrhiza Bunge by Agrobacterium
      mediated leaf-disk transformation method. Seven transgenic lines were obtained
      after kanamycin (50 mg/L) screening. Six positive lines were obtained by PCR
      amplification, and after four additional generations, one stable line was
      obtained by Southern hybridization. Transgenic plants had better growth states
      than control plants on mediums containing 1% NaCl and 8% PEG6000, which
      demonstrated that TaLEA1 played an important role in increasing the salt and
      drought tolerance of S. miltiorrhiza.

PMID- 17452796
TI  - The co-localization and possible interactions of integrin-like protein and alpha
      tubulin in the root cells of Zea mays.
AB  - Plant cell wall-plasma membrane-cytoskeleton (CW-PM-CSK) continuum plays
      important roles in the regulation of plant responses to environmental cues. It
      has been found in our previous study that an integrin-like protein identified in
      Arabidopsis and Zea mays plasma membrane mediates the interactions between cell
      wall and plasma membrane and cell responses to osmotic stress. In the present
      study, the co-localization of integrin-like protein and alpha-tubulin and their
      possible interactions were investigated in the root cells of maize using an
      indirect immunofluorescence technique combined with pharmacological approach. As
      compared with the control, after treatment with GRGDS, a synthetic peptide
      contained the RGD domain which binds specifically to integrin-like protein, the
      integrin-like protein was distributed more evenly over the plasma membrane and
      the density of alpha-tubulin array became lower. However, treatment with SDGRG, a
      GRGDS analog which does not contain the RGD domain, had no influences on them.
      Microtubule-depolymering or -stabilizing reagents exerted their effects either on
      the distribution over the plasma membrane or on the expression of integrin-like
      protein. The above results showed that the distribution of integrin-like protein
      on plasma membrane was closely linked to the alignment of microtubule arrays.
      Integrin-like protein mediates the interaction between cell wall and plasma
      membrane, and this interaction in return affected the alignment of microtubule
      arrays. Changes in cytoskeleton dynamics had significant effect on the
      distribution of integrin-like protein on the plasma membrane. These results
      strongly suggest that there are interactions between integrin-like protein and
      cytoskeleton in plant cells which are very complicated. It is worthy of extensive
      study to work out the mechanisms of plant responses to intracellular and
      extracellular signals.

PMID- 17452797
TI  - Starch accumulation and activities of key enzymes involved in starch synthesis in
      the grains of maize inbred lines with different starch contents.
AB  - Amylose, amylopectin and starch dynamic accumulation and key enzymes activities
      in the grains of 4 maize inbred lines (two high-starch ones and two low-starch
      ones) were studied. The amounts of amylose, amylopectin and starch in the grains
      of 4 maize inbred lines increased as sigmoid curves during grain filling period.
      The changes in amylose, amylopectin and starch accumulation rates followed single
      peaked curves, and reached their peaks in the 25-30 days after pollination (DAP).
      Changes in activities of adenosine diphosphoglucose pyrophosphorylase (ADPG
      PPase, EC 2.7.7.27), soluble starch synthase (SSS, EC 2.4.1.21) and starch
      granule-bound synthase (GBSS, EC 2.4.1.21) in the grains of 4 inbred lines
      appeared single-peaked curves with the peaks appearing 20-30 DAP. Changes in
      activities of starch-branching enzyme (Q-enzyme, EC 2.4.1.18) in the grains of
      high-starch inbred lines appeared single-peaked curves with the peak values at 20
      DAP, while the two low-starch inbred lines showed double-peaked curves with the
      peak values in the 15-20 DAP and 30-35 DAP. There was significant correlation
      between ADPG-PPase, SSS and GBSS activities. The results indicated that the Q
      enzyme had different expression in high- and low-starch maize inbred lines, and
      verified that ADPG-PPase, SSS and GBSS activities were significantly and
      positively correlated with amylose, amylopectin and starch accumulation rates.

PMID- 17452798
TI  - Changes in alpha-L-arabinofuranosidase activity in peel and pulp of banana (Musa
      sp.) fruits during ripening and softening.
AB  - Arabinose is one of the most dynamic cell wall glycosyl residues released during
      fruit ripening, alpha-L-arabinofuranosidase (alpha-Arab) are major glycosidases
      that may remove arabinose units from fruit cell wall polysaccharides. To find out
      whether alpha-Arab plays important roles in banana fruit softening, the enzyme
      activities in peel and pulp, fruit firmness, respiration rate and ethylene
      release rate were assayed during banana softening. The results showed that alpha
      Arab activities in banana pulp and peel increased slightly at the beginning of
      storage and reached their maxima when the fruit firmness decreased drastically,
      alpha-Arab activity increased by more than ten folds in both pulp and peel during
      ripening and alpha-Arab activities were higher in pulp than in peel. Treatment of
      banana fruits with ethylene absorbent postponed the time of reaching of its
      maxima of respiration and ethylene, enhanced the firmness of pup and decreased
      alpha-Arab activity in the peel and pulp. These results suggest that alpha-Arab
      induced the decrease of fruit firmness and played an important role in banana
      fruit softening, and its activity was regulated by ethylene.

PMID- 17452799
TI  - [Changes in cell wall components and cell wall-degrading enzyme activities of
      postharvest longan fruit during aril breakdown].
AB  - Longan (Dimocarpus longan Lour.) fruits are very susceptible to pericarp browning
      and aril breakdown, and postharvest aril breakdown is one of the most important
      factors degrading the quality and shorting storage life of longan fruit. Changes
      in aril breakdown index, cell wall components and cell wall-degrading enzyme
      activities in aril of longan cv. Fuyan fruits using sealed polyethylene film bags
      (0.015 mm thick) at (10+/-1) degrees C were investigated. The main results were
      as follows. Development of aril breakdown was higher with storage time (from day
      0 to day 36). Aril breakdown index was positively and significantly correlated
      with storage time (P<0.01). During development of aril breakdown, the total dry
      weight of the cell wall materials, protopectin, cellulose, semicellulose and cell
      wall protein contents of aril decreased progressively. The total dry weight of
      the cell wall materials, contents of protopectin, cellulose, semicellulose and
      cell wall protein of aril were all negatively correlated with aril breakdown
      index. There were low beta-galactosidase activity, and high activities of
      pectinesterase (PE), polygalacturonase (PG) and cellulase in aril of harvested
      fruit. PE activity in aril gradually decreased during development of aril
      breakdown. The activities of PG and cellulase in aril increased significantly
      during storage from day 6 to day 12 and from day 0 to day 12, respectively. The
      peaks enzyme activities of both PG and cellulase appeared on the 12th day after
      harvest, then the enzyme activity decreased; whereas, the activities of PE, PG
      and cellulase changed little from day 0 to day 24, and then rapidly decreased.
      The beta-galactosidase activity in aril decreased slightly during storage from
      day 0 to day 24. However, the beta-galactosidase activity increased significantly
      after day 24. Especially, the beta-galactosidase activity increased rapidly after
      30 d of storage, in the meantime, the activities of PE, PG and cellulase almost
      disappeared. From the results it can be seen that the development of aril
      breakdown was due to the degradation of cell wall components such as protopectin,
      cellulose, semicellulose and cell wall protein. The early and middle phases of
      development of aril breakdown were mainly brought about by the action of PE, PG
      and cellulase, whereas, beta-galactosidase played the key role at the late phase
      of aril breakdown.

PMID- 17452800
TI  - [Analysis of nonenzymic source of superoxide anion in pathogenic Xanthomonas
      oryzae pv. oryzae].
AB  - With electron spin resonance and chemical assay, the production of superoxide
      anion in the Xanthomonas oryzae pv. oryzae strain OS-14 suspension is
      extracellularly localized. It was found that superoxide anion produced in the
      filtrate. It was confirmed that peptide or enzyme did not contribute to the
      production of superoxide anion in the filtrate of OS-14. Organic acids were shown
      to be the primary source of superoxide anion produced in the filtrate of OS-14.
      These results indicated that non-enzymic molecules might be another source of
      superoxide anion produced by Xanthomonas oryzae pv. oryzae, in addition to
      enzymes, which suggested the multiform generation of superoxide anion.

PMID- 17452801
TI  - [Physiological function of the qPGWC-9 related to high percentage of rice grains
      with Chalkiness].
AB  - Percentage of grains with chalkiness (PGWC), one of the important traits
      assessing rice grain appearance quality, belonged to qualitative trait controlled
      by many genes. Our previous study identified a novel quantitative trait locus
      (QTL), namely qPGWC-9, related to high PGWC using chromosomal segment
      substitution line (CSSL) population. qPGWC-9 was shown to be expressed stably in
      eight environments. AIS82 which carried a IR24 chromosomal segment corresponding
      to qPGWC-9 in the Asominori genetic background was selected and analyzed to
      clarify the physiological function of qPGWC-9 from the relationship of source and
      sink of carbohydrates. It showed that AIS82 had higher PGWC than Asominori
      (control variety with low PGWC). The net photosynthetic rate of flag leaf of
      AIS82 showed no significant difference from that of Asominori, so photosynthetic
      ability in flag leaf was not directly related with high PGWC in AIS82. But, the
      changes in pattern of activity of the key enzymes associated with starch
      synthesis were different in these plants. Activities of some key enzymes in
      starch synthesis in AIS82 changed more radically than those in Asominori. These
      results suggest that qPGWC-9 might determine the activities of some enzymes
      associated with starch synthesis and therefore affect the degree of grain
      chalkiness.

PMID- 17452802
TI  - [A highly efficient system for induction of female flowers in derooted seedlings
      of Cucumis sativus L. grown on the medium].
AB  - This paper reported the synergistic effect of KT and IAA, and the effects of age
      of seedlings, length of hypocotyls, nitrogen contents and NH(+)(4)-N/TN ratio on
      the induction of female flowers in derooted seedlings of Cucumis sativus L. for
      the establishment of an efficient system for the induction of female flowers.
      When cultured on MS basal medium supplemented with KT 3.0 mg/L and IAA 0.01 mg/L,
      an induction rate of 28% was obtained for the 7-day-old derooted seedlings with
      1/2 hypocotyl, 12% and 26% higher than when cultured with KT 3.0 mg/L alone and
      IAA 0.01 mg/L alone, respectively, while no female flowers was formed on the
      control medium, which indicates that KT and IAA have an evident synergistic
      effect on the induction of female flowers. Experiment was done with N
      concentration of 60-90 mmol/L or with NH(+)(4)-N/TN ratio of 12.5%-50% (total N
      kept at 80 mmol/L), with lengths of hypocotyls of 0-4/4, and with different ages
      of seedlings of 5-8-day-old, the highest induction rate of 40%, 48% and 57% for
      female flowers was achieved on medium of N 80 mmol/L (NH(+)(4)-N/TN 37.5%), from
      seedlings with 1/4 hypocotyl and from the treatment using 6-day-old seedlings
      respectively.

PMID- 17452803
TI  - [Effects of salt stress on the contents of chlorophyll and organic solutes in
      Aeluropus littoralis var. sinensis Debeaux].
AB  - After seedlings of Aeluropus sinensis var. sinensis Debeaux were treated with
      different NaCl concentrations (0-200 mmol/L) for 14 days, some physiological
      indexes were measured. The higher the NaCl concentration, the more the growth of
      A. sinensis was inhibited. The increase in root/shoot ratio suggests that the
      shoots are more sensitive to salinity than the roots. The diminished leaf area
      may reduce the transpiration rate, and the root mainly grew longitudinally, which
      may help the root to reach the water source under the high salinity conditions.
      Chl a contents increased, so did Chl b, but the Chl a/Chl b ratio declined, which
      implies the stimulation of Chl a accepted from NaCl is smaller than that of Chl
      b. After salt treatment, the organic solute contents increased (P<0.05), the
      proline, amino acids and soluble sugar contents increased more than organic
      acids, the increase in soluble carbohydrate may inhibit photosynthesis in
      feedback. The percentage of sucrose in soluble carbohydrates increased too.
      Although the organic dry weight of whole plant declined, the proportion of
      organic dry weight in total dry weight increased, and the osmotic potential of
      plant cell juice declined, which implies that the contribution of organic matter
      to osmotic adjustment increased with salinity. That is, A. sinensis had ability
      to tolerate salinity to a certain degree.

PMID- 17452804
TI  - [Function of the putative Na+/H+ antiporter gene PeNhaD1 from salt-resistant
      Populus euphratica Oliv].
AB  - Yeast complementation experiments were carried out to define the possible
      function of PeNhaD1, a Na(+)/H(+) antiporter gene from Populus euphratica Oliv.,
      a salt resistant tree. PeNhaD1 was introduced to the Saccharomyces cerevisiae
      mutant strain ANT3 (Deltaena1-4::HIS3 Deltanha1::LEU2), which lacks the plasma
      membrane Na(+)/H(+) antiporter gene ScNHA1 or GX1 (Deltanhx1::TRP1), which lacks
      tonoplast Na(+)/H(+) antiporter gene ScNHX1. Our results showed that PeNhaD1
      rescued the normal growth of ANT3 in the presence of high salt (80 mmol/L NaCl on
      solid medium or 400 mmol/L in liquid medium, pH 6.0), but not that of GX1,
      suggesting that PeNhaD1 may play a role in salt tolerance of Populus euphratica
      by maintaining the capacity for salt exclusion under saline condition.

PMID- 17452805
TI  - Improvement of postischemic dopaminergic dysfunction by edaravone, a free radical
      scavenger.
AB  - Effects of a free radical scavenger, edaravone (3-methyl-1-phenyl-2-pyrazolin-5
      one), on ischemia/reperfusion-induced dysfunctions of rat striatal dopaminergic
      neurons were examined using in vivo brain microdialysis. During transient
      forebrain ischemia, dopamine levels in dialysates were elevated 140-fold above
      controls but rapidly recovered after reperfusion. The increase in dopamine levels
      induced by high K+ stimulation after reperfusion was far smaller than that of the
      controls. Pretreatment with edaravone but not post-treatment dose-dependently
      improved the response to high K+ but not the massive dopamine increase during
      ischemia. These results suggest that free radicals produced during ischemia play
      more important roles in ischemia/reperfusion-induced dysfunctions of dopaminergic
      neurons.

PMID- 17452806
TI  - Cell-cycle-dependent regulation of Ca2+-activated K+ channel in Jurkat T
      lymphocyte.
AB  - Small-conductance Ca2+-activated K+ (SK2) channel plays an important role in the
      activation of Jurkat T-lymphocytes by maintaining electrical gradients for the
      sustained Ca2+ influx. Apamin-sensitive K+ current was significantly decreased
      with cell-cycle progression from G0/G1 into G2/M phases, and protein expression
      of SK2 channels showed parallel down-regulation, with its highest expression at
      early G0/G1 phase. In the G0/G1 phase, the apamin-sensitive component of
      thapsigargin-induced Ca2+ influx was significantly larger than that in the G2/M
      phase. These observations suggest that SK2-channel activation may largely
      contribute to the sustained Ca2+ influx in the G0/G1 phase in comparison of that
      in the G2/M phase in Jurkat T-lymphocytes.

PMID- 17452807
TI  - Nitric oxide-independent cGMP efflux in the striatum of rats exposed to carbon
      monoxide as determined by microdialysis.
AB  - Extracellular cGMP in the striatum of rats exposed to 3000 ppm carbon monoxide
      (CO) or 8% O2 was decreased during the early period of exposure. Thereafter,
      extracellular cGMP in rats exposed to CO, but not 8% O2, was transiently
      increased. A nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine, strongly
      reduced the steady-state level of extracellular cGMP in the striatum, indicating
      a primary role of NO in cGMP production. However, it failed to suppress the CO
      induced increase in extracellular cGMP in the striatum. These findings suggest
      that CO may stimulate cGMP production in rat striatum independently of NO and
      hypoxia.

PMID- 17452808
TI  - Effects of certain antiepileptics on behavioral and electromyographic seizure
      patterns induced by maximal electroshock in mice.
AB  - The changes of electromyographic activity (EMG seizure) induced by maximal
      electroshock were studied in comparison with those of behavioral seizures in
      mice. In addition, the effects of certain antiepileptics on behavioral seizures
      and EMG seizure induced by maximal electroshock were also studied. High amplitude
      with high frequency EMG seizure was observed in parallel with the appearance of
      tonic extensor (TE) seizure and an intimate relationship was observed between the
      two parameters. On the other hand, to investigate the intensity of TE seizure,
      the product of the amplitude and the duration in EMG seizure was calculated, and
      the effects of antiepileptics on the magnitude of EMG seizure were investigated.
      As a result, a significant difference was observed at the doses of antiepileptics
      that showed no significant effects on the durations of TE and EMG seizures; that
      is, phenytoin, phenobarbital, topiramate, and carbamazepine showed significant
      effects on the magnitude of EMG seizure at doses of 5, 2, 10, and 5 mg/kg,
      respectively. From these findings, it may be concluded that this index, that is,
      the magnitude of EMG seizure induced by maximal electroshock, is a more reliable
      and highly sensitive method for the assessment of the potential activity of
      antiepileptics.

PMID- 17452809
TI  - Role of caspase-12 in amyloid beta-peptide-induced toxicity in organotypic
      hippocampal slices cultured for long periods.
AB  - Amyloid beta (Abeta) toxicity has been implicated in cell death in the
      hippocampus, but its specific mechanisms are poorly understood. In this study,
      Abeta-induced cell death was investigated in organotypic hippocampal slice
      cultures (OHCs) that were cultured for various periods in vitro. There were no
      obvious histological differences among slices cultured for 3 to 7 weeks in vitro.
      Although there was little neurotoxicity after treatment with Abeta25-35 in OHCs
      cultured for relatively shorter periods (3-5 weeks), age-dependent cell death was
      evident in OHCs cultured for relatively longer periods (6-7 weeks) after exposure
      to Abeta25-35. In OHCs cultured for 7 weeks, S-allyl-L-cysteine (SAC), a
      component of aged garlic extract, protected the cells in areas CA1 and CA3 and
      the dentate gyrus from Abeta25-35-induced toxicity. The immunoreactivity of
      cleaved caspase-12 was increased whereas that of glucose-regulated protein 78 was
      not altered after exposure to Abeta25-35. The increases in the cleaved caspase-12
      were also reversed by simultaneously applied SAC. These results suggest that OHCs
      cultured for relatively longer periods are more susceptible to Abeta-induced
      toxicity and that the Abeta-induced cell death involves caspase-12-dependent
      pathways. It is also suggested that SAC is able to protect against the Abeta
      induced neuronal cell death through the inhibition of the caspase-12-dependent
      pathway.

PMID- 17452810
TI  - Intrathecally administered D-cycloserine produces nociceptive behavior through
      the activation of N-methyl-D-aspartate receptor ion-channel complex acting on the
      glycine recognition site.
AB  - Intrathecal (i.t.) administration of D-cycloserine (100 and 300 fmol), a partial
      agonist of the glycine recognition site on the N-methyl-D-aspartate (NMDA)
      receptor ion-channel complex, produced a behavioral response mainly consisting of
      biting and/or licking of the hindpaw and the tail along with slight hindlimb
      scratching directed toward the flank in mice, which peaked at 5 - 10 min and
      almost disappeared at 15 min after the injection. The behavior induced by D
      cycloserine (300 fmol) was dose-dependently inhibited by an intraperitoneal
      injection of morphine (0.5-2 mg/kg), suggesting that the behavioral response is
      related to nociception. The nociceptive behavior was also dose-dependently
      inhibited by i.t. co-administration of 7-chlorokynurenic acid (0.25-4 nmol), a
      competitive antagonist of the glycine recognition site on the NMDA receptor ion
      channel complex; D-(-)-2-amino-5-phosphonovaleric acid (62.5-500 pmol), a
      competitive NMDA receptor antagonist; MK-801 (62.5-500 pmol), an NMDA ion-channel
      blocker; ifenprodil (0.5-8 nmol); arcaine (31-125 pmol); and agmatine (0.1-10
      pmol), all being antagonists of the polyamine recognition site on the NMDA
      receptor ion-channel complex. However, [D-Phe7,D-His9]-substance P(6-11), a
      specific antagonist for substance P (NK1) receptors, and MEN-10,376, a tachykinin
      NK2-receptor antagonist, had no effect on D-cycloserine-induced nociceptive
      behavior. These results in the mouse spinal cord suggest that D-cycloserine
      induced nociceptive behavior is mediated through the activation of the NMDA
      receptor ion-channel complex by acting on the glycine recognition site and that
      it does not involve the tachykinin receptor mechanism.

PMID- 17452811
TI  - Prolonged esophagitis after primary dysfunction of the pyloric sphincter in the
      rat and therapeutic potential of the gastric pentadecapeptide BPC 157.
AB  - Seven or fourteen days or twelve months after suturing one tube into the pyloric
      sphincter (removed by peristalsis by the seventh day), rats exhibit prolonged
      esophagitis with a constantly lowered pressure not only in the pyloric, but also
      in the lower esophageal sphincter and a failure of both sphincters. Throughout
      the esophagitis experiment, gastric pentadecapeptide BPC 157 (PL 14736) is given
      intraperitoneally once a day (10 microg/kg, 10 ng/kg, last application 24 h
      before assessment), or continuously in drinking water at 0.16 microg/ml, 0.16
      ng/ml (12 ml/rat per day), or directly into the stomach 5 min before pressure
      assessment (a water manometer connected to the drainage port of a Foley catheter
      implanted into the stomach either through an esophageal or duodenal incision).
      This treatment alleviates i) the esophagitis (macroscopically and
      microscopically, at either region or interval), ii) the pressure in the pyloric
      sphincter, and iii) the pressure in the lower esophageal sphincter (cmH2O). In
      the normal rats it increases lower esophageal sphincter pressure, but decreases
      the pyloric sphincter pressure. Ranitidine, given using the same protocol (50
      mg/kg, intraperitoneally, once daily; 0.83 mg/ml in drinking water; 50 mg/kg
      directly into the stomach) does not have an effect in either rats with
      esophagitis or in normal rats.

PMID- 17452812
TI  - Vasodilating mechanisms of levosimendan: involvement of K+ channels.
AB  - Levosimendan, a novel agent developed for the treatment of acute and
      decompensated heart failure, exerts potent positive inotropic action and
      peripheral vasodilatory effects. The mechanism of vasodilation by levosimendan
      may involve reduction of Ca2+ sensitivity of contractile proteins in vascular
      smooth muscle, the lowering of intracellular free Ca2+, the potential inhibition
      of phosphodiesterase (PDE) III, and an opening of K+ channels. Although the
      importance and relative contribution of each of these mechanisms of
      vasorelaxation is unclear and may be different in various vessels and dependent
      on the dose of levosimendan, the important roles of K+-channel opening and Ca2+
      desensitization in vascular smooth muscle are obvious, whereas the role of PDE
      inhibition remains to be defined. This review article briefly discusses the
      current research data on the mechanism of levosimendan-induced vasodilation with
      an emphasis on the types of the blood vessels and the K+ channels. It also
      summarizes the current experimental and clinical knowledge of the use of
      levosimedan in the treatment of heart failure.

PMID- 17452813
TI  - From Krukenberg to today: the ever present problems posed by metastatic tumors in
      the ovary. Part II.
AB  - This is the second of a two-part consideration of metastatic tumors to the ovary.
      Here, the matter is considered in 16 categories, largely site-specific. The first
      tumor discussed is gastric carcinoma of intestinal-type whose ovarian
      manifestations have been the subject of a recent paper which emphasized its
      differences from the Krukenberg tumor. Coverage of intestinal adenocarcinoma
      emphasizes the landmark 1987 paper of RH Lash and WR Hart. The section on
      pancreatic neoplasms reemphasizes the problems caused by metastatic ductal
      carcinoma, considered primarily in Part I, and discusses less common issues such
      as spread of neuroendocrine and acinar cell carcinomas. The limited information
      on spread of tumors of the gallbladder and extrahepatic bile ducts is then
      reviewed before more detailed consideration of hepatic neoplasms, prompted by
      recent contributions on hepatocellular carcinoma and intrahepatic
      cholangiocarcinoma, the latter based on significant experience with this problem
      in Thailand. The section on appendiceal neoplasms highlights ovarian spread of
      diverse tumors ranging from typical intestinal-type adenocarcinoma to signet-ring
      cell carcinomas with various patterns which in the ovary may prompt diagnoses
      such as a goblet cell (mucinous) carcinoid tumor, but whose ovarian features
      place them in the category of a Krukenberg tumor. The diverse problems in
      differential diagnosis of carcinoid tumor (provoked by nested, acinar, and other
      patterns, including folliclelike spaces) are then reviewed. The section on breast
      cancer emphasizes that, although usually a manifestation of late stage disease
      and often not bulky in the ovaries, metastatic breast cancer may form large
      masses which can represent the clinical presentation. That patients with breast
      cancer have an increased risk of primary ovarian cancer and that the latter is
      more common than secondary spread of breast cancer is noted. The section on lung
      tumors largely reflects information in a recent paper that small cell carcinoma
      and adenocarcinoma are the lung cancers that spread to the ovary most commonly.
      The extremely broad differential diagnosis posed by metastatic malignant melanoma
      ranging from that of an oxyphilic tumor, to a small cell tumor, to a follicle
      forming neoplasm, is then considered. The sections on renal cell carcinoma and
      other urinary tract neoplasms emphasize the differential diagnosis of metastatic
      clear cell carcinoma and primary clear cell carcinoma, an issue usually
      resolvable by an awareness of the various features of the ovarian variant, rarely
      or never seen in the renal variant. The section on metastatic sarcomas discusses
      endometrial stromal sarcomas, gastrointestinal stromal neoplasms, and
      miscellaneous other sarcomas. The endometrial stromal tumors are problematic
      largely because the history of a primary tumor may be remote, in the ovaries the
      typical growth and vascular pattern of endometrial stromal neoplasms is not
      always conspicuous, and some endometrial stromal sarcomas in the ovary show sex
      cordlike patterns of growth. Recent information has indicated that
      gastrointestinal stromal tumors may rarely have significant ovarian
      manifestations and if the primary neoplasm is overlooked, the ovarian tumor may
      be misdiagnosed, usually as an ovarian fibromatous tumor, but potentially as
      another primary neoplasm. The sections on ovarian spread of uterine carcinomas
      emphasize the problems owing to cervical adenocarcinomas, which have a greater
      tendency to involve the ovaries than squamous cell carcinomas and can simulate
      primary mucinous or endometrioid cancers. The final neoplasms considered are
      malignant mesothelioma and the desmoplastic small round cell tumor. The
      microscopic features of malignant mesothelioma are so different from those of
      primary ovarian carcinoma in most instances that the diagnosis should be readily
      established on routine microscopic evaluation. The differential diagnosis of the
      desmoplastic small round cell tumor is more complex because of the greater
      overlap with the many other small cell malignant tumors that may involve the
      ovaries primarily or secondarily. Nonetheless, differences exist in most cases
      and awareness of the entity should lead to consideration of the desmoplastic
      neoplasm, particularly in a young female. In this area, as in a number of others
      considered in the review, immunohistochemistry may play a significant, sometimes
      crucial, role. However, as pointed out in brief concluding remarks, despite the
      aid of that modality, as in surgical pathology overall, careful consideration of
      the clinical background, distribution of disease, gross characteristics and
      spectrum of routine microscopic findings, will lead to the correct diagnosis in
      the majority of cases and at the very least lead to formulation of a considered
      differential diagnosis such that use of special techniques may be judicious and
      those results placed in context of the time-honored clinical and pathologic
      features.

PMID- 17452814
TI  - Distinguishing gastrointestinal stromal tumors from their mimics: an update.
AB  - Since the discovery of activating KIT mutations in gastrointestinal stromal
      tumors (GISTs) in 1998 and the subsequent demonstration that some malignant GISTs
      respond to targeted therapy with imatinib, it has become increasingly important
      for pathologists to correctly diagnose GISTs and separate them from their
      potential mimics in the gastrointestinal tract and abdominal cavity. Some
      mesenchymal tumors, such as leiomyomas of the muscularis mucosae, are easily
      distinguished from GIST on the basis of their anatomic location and morphologic
      appearance. Others, such as gastrointestinal schwannomas, can significantly
      overlap with GIST in their gross appearance and morphology and require a panel of
      immunostains for correct diagnosis. This article will review the most common
      mimics of GISTs: desmoid tumors, smooth muscle tumors (leiomyomas and
      leiomyosarcomas), gastrointestinal schwannomas, inflammatory fibroid polyps, and
      solitary fibrous tumors. Pertinent differences between each of these tumors and
      GIST in terms of gross appearance, histologic features, and immunophenotype will
      be emphasized. It is important to separate GISTs from these potential mimics
      because their treatment and prognosis can differ markedly.

PMID- 17452815
TI  - Immunodeficiency-related Hodgkin lymphoma and its mimics.
AB  - Classic Hodgkin lymphoma (CHL) in patients with underlying immunodeficiency
      disorders frequently differs from that in the immune competent population in
      terms of its clinical behavior and pathologic features. Moreover, differential
      from Hodgkin-like lymphoid proliferations may be problematic. Topics under review
      include: (a) CHL posttransplant lymphoproliferative disorders, (b) CHL in
      HIV/AIDS, (c) Hodgkin variant of Richter syndrome in chronic lymphocytic leukemia
      in association with fludarabine therapy, (d) CHL in other immunodeficiency states
      including methotrexate-associated lymphoproliferative disorder in patients with
      rheumatoid arthritis and primary immune deficiencies, and (e) Hodgkin-like
      lymphoid proliferations including senile Epstein-Barr virus+ B-cell
      lymphoproliferative disorder. Also under consideration is the pathogenesis of
      these disorders with an emphasis on the role of Epstein-Barr virus.

PMID- 17452816
TI  - Angiotropic melanoma and extravascular migratory metastasis: a review.
AB  - How metastases develop is poorly understood. The concept of intravascular
      dissemination of cancer cells has been widely accepted as a central paradigm. In
      addition to this explanation, however, other mechanisms may be operable.
      Ultrastructural studies have identified in malignant melanoma an angio-tumoral
      complex, in which tumor cells are linked to endothelium by a matrix containing
      laminin without evidence of intravasation. This observation has suggested that
      melanoma cells may migrate along the external surface of vessels and other
      anatomic structures, a mechanism termed "extravascular migratory metastasis"
      (EVMM). Angiotropism (melanoma cells cuffing the external surface of vessels) is
      the histopathologic counterpart of the angio-tumoral complex. The authors have
      recently drawn attention to the importance of angiotropism as a biologic
      phenomenom and prognostic factor in melanoma and as a likely correlate of EVMM.
      In addition, recent experimental studies strongly suggest a correlation of
      angiotropism of melanoma cells with EVMM. These studies, including cocultures of
      melanoma cells with capillarylike structures in vitro and the growth of green
      fluorescent protein-labeled melanoma cells in the shell-less chick
      chorioallantoic membrane model, have demonstrated the migration of angiotropic
      melanoma cells along the vascular channels, supporting the concept of EVMM. The
      new field of EVMM reviewed in this paper may prove useful in elucidating the
      molecular interactions involved in melanoma metastasis.

PMID- 17452817
TI  - Renal pathology in the pediatric transplant patient.
AB  - Renal transplantation is a therapeutic goal for children with advanced chronic
      kidney disease. There are many causes of renal dysfunction in children with
      allografts--the transplanted kidney can develop a variety of morphologic
      alterations leading to dysfunction. Evaluation of the kidney biopsy is one of the
      best methods of determining the cause of graft dysfunction. Rejection is a major
      cause of renal allograft failure in children. The morphologic hallmarks of acute
      antibody-mediated and cell-mediated rejection and chronic allograft nephropathy
      have been codified in classification strategies that are useful in adults and
      children. Viral infection and Epstein-Barr virus-driven posttransplant
      lymphoproliferative disease also occur in the pediatric transplanted kidney. Drug
      toxicity from immunosuppressive agents also causes characteristic morphologic
      alterations in the renal allograft. As the survival of pediatric heart and liver
      transplant patients improves, the incidence of immunosuppression therapy-related
      disease in the native kidney in these patients will likely become more important
      clinically. In addition to renal lesions related to the allograft state,
      glomerular disease can recur or occur de novo in renal allografts. Here, we
      describe the pathology of the more common morphologic lesions in kidneys of
      children with a renal allograft.

PMID- 17452818
TI  - Review of the clinicopathologic features of fibrolamellar carcinoma.
AB  - Since its first description 50 years ago, fibrolamellar carcinomas (FLCs) have
      been recognized as a unique type of primary liver cancer. FLCs occur principally
      in children and young adults and are not associated with chronic liver disease.
      Their etiology is unknown. The tumor is made up of large polygonal cells
      containing abundant eosinophilic cytoplasm, large vesiculated nuclei, and large
      nucleoli, with tumor cells that are embedded in lamellar bands of fibrosis.
      Although rare, the most common variant of FLC shows areas of glandular type
      differentiation with mucin production. The uniqueness of FLC extends to their
      molecular findings, as they show no evidence for involvement by many of the major
      pathways and genes that are dysregulated in typical hepatocellular carcinoma,
      including alpha-fetoprotein, TP53 mutations, and beta catenin mutations. FLCs are
      not indolent tumors, but have an overall better prognosis than hepatocellular
      carcinomas of the usual sort because of the younger age at presentation and lack
      of cirrhosis. The most important prognostic feature is resectability. Although
      their morphologic appearance on routine stains is well defined, their etiology is
      still unknown and much of their molecular biology remains poorly described and
      awaits future investigation.

PMID- 17452819
TI  - Gastric mucosal calcinosis: clinicopathologic considerations.
AB  - Generally, gastric mucosal calcinosis (GMC) is only rarely encountered in routine
      biopsies. GMC may be classified as dystrophic, metastatic, or idiopathic.
      Metastatic calcification represents the most frequently encountered subtype, and
      refers to the deposition of calcium salts on largely normal tissues in the
      setting of an abnormal serum biochemical environment (hypercalcemia,
      hyperphosphatemia, and/or an elevated CaxPO4 product). In contrast, dystrophic
      calcification implies calcification in inflammed, fibrotic, or otherwise altered
      tissue in the setting of a normal biochemical environment. The gastric mucosa,
      along with the kidneys and lungs, are preferential sites for metastatic
      calcification, a finding that has been attributed to the relative intracellular
      alkalinity at these sites. In addition to the wide variety of hypercalcemia
      and/or hyperphosphatemia-causing clinical conditions, GMC has also been
      associated with atrophic gastritis, hypervitaminosis A, organ transplantation,
      gastric neoplasia, uremia with eucalcemia/euphosphatemia, and the use of aluminum
      containing antacids, citrate-containing blood products, isotretinoin, and
      sucralfate. Although GMC has rarely been associated with epigastric pain and/or
      dyspepsia, most come to clinical attention owing to their accumulation of bone
      seeking radiopharmaceuticals or represent a postmortem finding. The precise
      significance or mechanistic basis for GMC remains to be elucidated. However,
      their presence in gastric biopsies should be reported, as they may serve as an
      indicator for generalized metastatic calcification, especially in organs where
      they may be fatal, such as the heart. Furthermore, some examples of systemic
      calcification are reversible with normalization of biochemical parameters, which
      highlights the need for pathologists to report this finding when encountered in a
      premortem gastric biopsy.

PMID- 17452827
TI  - An objective assessment of botulinum toxin A effect on superficial skin texture.
AB  - The botulinum toxin A (BTX-A) role on elimination of hyperkinetic wrinkles is
      consolidated, although relying on subjective methods of assessment. A prospective
      open-label study was performed on 10 patients to objectively analyze superficial
      skin texture changes caused by BTX-A in the glabellar area. Skin areas were
      reproduced by silicon replica technique at baseline, 1 month, and 6 months after
      treatment. Takahashi's parameters (roughness, anisotropy, microsulcus number, and
      width) were obtained from scanning electron microscopy (SEM) analysis and
      compared using the Wilcoxon signed rank test. SEM images showed skin texture
      changes, and software analysis gave parameters for statistical analysis, allowing
      an objective evaluation. Statistically significant parameter modifications were
      evidenced. BTX-A effectiveness in wrinkle treatment was confirmed, and no
      differences in skin texture parameters from baseline to toxin action end were
      noted.

PMID- 17452828
TI  - Botulinum toxin in closed treatment of mandibular condylar fracture.
AB  - BACKGROUND: The topic of condylar injury in adults has generated more discussion
      and controversy than any other in the field of maxillofacial trauma. The
      treatment of condylar fractures in adults is still a highly debated theme.
      METHODS: Patients with unilateral subcondylar or condylar neck fractures of the
      mandibula without any significant angulation of the condylar head were managed
      with closed-treatment protocol. Closed treatment was applied through the
      injection of 100 units of botulinum toxin A, diluted to a concentration of 20
      IU/mL, into the muscles of mastication of the fractured side. Masseter and
      anterior fibers of temporalis muscles were reached through percutaneous extraoral
      route and 30 IU of the toxin was injected to each muscle. Additional 40 IU of the
      toxin was injected around the fractured bone fragments through transmucosal
      intraoral route to paralyze medial and lateral pterygoid muscles as much as
      possible. An asymmetric occlusal splint was applied for maxillomandibular
      fixation to restore the vertical height for 10 days. Functional therapy with
      intermaxillary guiding elastics was advocated for 2 months. RESULTS: There were
      no complications related to either toxin injections or splint application
      procedures. The toxin was effective on all occasions. Fractured condylar process
      and ramus of the mandibula were in good approximation and remained in reduced
      positions. None of the patients had any occlusal disturbance, mandibular
      asymmetry, or joint dysfunction in the follow-up period. CONCLUSIONS: We believe
      that modification of treatment options concerning the clinical situation of the
      patients is the best method for condylar injury. The purpose of this study is to
      present and discuss the results achieved in closed treatment of a selected group
      of patients with mandibular condylar fractures to whom botulinum toxin A was
      injected to relieve the spasm of muscles of mastication, along with special
      splint application.

PMID- 17452829
TI  - Flap choices to treat complex severe postburn hand contracture.
AB  - Many regions of the hand are affected seriously in the patients with complex
      severe postburn hand contractures. Multiple flap choices should be in count to
      treat complex severe postburn hand contractures affectively. We preferred dorsal
      ulnar flap for palmar region, cross-finger flap, side finger flap, and combined
      use of both for flexion contracture of the fingers, and rhomboid flap for web
      contractures. Eight patients having complex severe postburn hand contractures
      were treated between November 2001 and February 2005. The maximum improvements of
      the joint extensions were 75 degrees for median of digits metacarpophalangeal
      joint and 105 degrees for proximal interphalangeal joint. Grasp function of the
      hand dramatically improved, and the bulk of the flap did not interfere grasping.
      Complex severe postburn hand contracture can be treated sufficiently with dorsal
      ulnar flap, combined use of cross-finger and side finger transposition flap, and
      rhomboid flap.

PMID- 17452830
TI  - The Suzuki frame for complex intra-articular fractures of the proximal
      interphalangeal joint of the fingers.
AB  - In 1994, Suzuki et al proposed the pins-and-rubbers traction system, a new
      dynamic distraction technique for difficult complex intra-articular fractures of
      the digits of the hand. From February 1999 to April 2003, we used the Suzuki
      frame for 15 complex fractures of the proximal interphalangeal joint of the
      fingers. The mean follow-up period was 18 months. Four patients missed their
      follow-up. In the remaining 11 patients, the mean active range of motion achieved
      following treatment was 84 degrees in the proximal interphalangeal joint finger
      injuries.

PMID- 17452831
TI  - Avoiding pitfalls of the pins and rubbers traction technique for fractures of the
      proximal interphalangeal joint.
AB  - Treatment of comminuted intra-articular fractures of the digits with the Pins and
      Rubbers Traction System (PRTS) has been reported in many small series to give
      good results. Our experience in more than 40 cases with this technique, however,
      has not always been favorable. We analyzed outcomes and complications of PRTS
      treatment in 25 patients with proximal interphalangeal joint fractures reviewed
      at a mean 13 months (range, 6-52 months) after surgery. Mean arc of motion at
      this joint was 67.2 degrees (range, 35-110 degrees ) and at the distal
      interphalangeal joint 40.7 degrees (range, 0-90 degrees ). The latter was
      immobile in 3 (12%) and 7 patients (28%) had superficial pin track infections.
      Loss of extension at both joints was a major factor in poor outcomes. Based on
      this experience, we suggest ways of avoiding common pitfalls of PRTS treatment.
      Concurrent internal fixation impacts significantly on interphalangeal joint
      stiffness.

PMID- 17452832
TI  - A new surgical technique for the correction of pincer nail deformity.
AB  - BACKGROUND: Pincer nail is a rare deformity characterized by transverse
      overcurvature of the nail that increases distally. Many conservative and surgical
      treatment modalities have been recommended, but there is not a worldwide accepted
      technique for long lasting treatment of this deformity yet. PURPOSE: A new
      surgical technique for the treatment of pincer nail deformity is described.
      MATERIAL AND METHOD: In this procedure, after the osteophyte located on the
      dorsal surface of the distal phalanx is removed to provide a flat surface for the
      nail bed, the distal part of the nail bed is enlarged in a transverse direction
      by using a modified 5-flap z-plasty technique. Over 2 years, this technique has
      been performed on 15 toes in 8 patients. RESULTS: In all patients, the deformity
      was eliminated successfully with no recurrence in 2 years of follow up. The
      growing nail turned back into its natural form and all clinical signs and
      symptoms of the pincer nail deformity were relieved. CONCLUSIONS: Widening and
      flattening the nail bed provide a longlasting effective treatment of the pincer
      nail deformity with an excellent esthetic result. Pain and episodes of infection
      is relieved perfectly with this new technique.

PMID- 17452833
TI  - Freestyle perforator-based V-Y advancement flap for reconstruction of soft tissue
      defects at various anatomic regions.
AB  - BACKGROUND: Perforator flap surgery has gained great popularity in the last
      decade because surgeons can prepare freestyle flaps in anywhere on the body if
      they find a perforator supplied to the flap. One of the basic principles of
      reconstructive surgery is that superior results can be obtained for color and
      texture match if immediately adjacent soft tissue is used to repair a defect. V-Y
      advancement flaps are used successfully based on this principle, but the degree
      of mobility of a V-Y advancement flap is dependent on the laxity of the
      underlying subcutaneous tissue. This is an important disadvantage of traditional
      V-Y advancement flap and limits its use. METHODS: We used V-Y advancement flaps
      as perforator-based to overcome mobility restriction problem. The authors used 26
      perforator-based V-Y advancement flaps in 24 consecutive patients for coverage of
      defects located at sacral (4), thigh (6), abdominal wall (3), inguinal (3), back
      (4), leg (2), and trochanter (2) regions. There were 14 female and 10 male
      patients with a mean age of 48.3 years (range, 22-70 years). RESULTS: The
      patients were followed up for a mean period of 14.2 months (range, 9-21 months).
      The size of the defects ranged from 3 x 5 cm to 15 x 20 cm. All flaps survived
      completely (92.4%) except 2 in which one of them had undergone total necrosis and
      the other had marginal necrosis. Fifteen flaps (57.6%) were elevated based on 2
      perforators, 7 flaps (26.9%) were used with only one perforator, and the
      remaining 4 (15.5%) had 3 perforators. CONCLUSIONS: Perforator-based V-Y
      advancement flaps are safe and very effective for coverage of defects in which
      closure is impossible with a standard V-Y advancement flap. Dissection of the
      perforator or perforators offers remarkable excursion to the V-Y flap with
      minimal donor site morbidity. These axial pattern flaps can be used successfully
      with good esthetic and functional results at various regions of the body if there
      is any detectable perforator.

PMID- 17452834
TI  - Our experience in lower limb reconstruction with perforator flaps.
AB  - The application of Taylor's concept about body angiosomes, referred to tissue
      transfers, has meant that the development of the perforator flaps and muscles is
      no longer needed as a carrier of skin flap vascularity. In this paper, we revise
      59 lower limb reconstructions with local and free perforator flaps performed in
      the last 5 years, and a basic reconstructive algorithm is also suggested to help
      with the management of the lower limb soft tissue reconstruction with perforator
      flaps. The advantages of the perforator flaps are (1) muscles and their function
      are preserved; (2) the main vascular trunks are spared; (3) it is possible to
      make a more specific reconstruction, replacing "like with like" (even performing
      compound or chimeric flaps); (4) the donor site can often be closed primarily;
      (5) the general morbidity is reduced; (6) a better cosmetic result can be
      achieved.

PMID- 17452835
TI  - The reverse sural fasciomusculocutaneous "mega-high" flap: a study of 20
      consecutive flaps for lower-limb reconstruction.
AB  - The reverse sural artery flap was initially described as a fasciocutaneous flap
      and has become an acceptable technique of lower-limb reconstruction. The flap was
      recently modified to include a midline gastrocnemius muscle cuff around the sural
      pedicle in the upper part of the leg, and hence improving its blood supply. Large
      lower-limb defects require "mega" flaps (including the whole width of the calf)
      harvested "high" all the way up to the popliteal fossa. The following study was
      designed to answer the following question: Is this "mega-high" reverse sural
      fasciomusculocutaneous flap reliable? A total of 20 consecutive male patients
      with large lower-limb defects who were reconstructed with this flap were
      included. The skin of the whole width of the upper calf (extending 2-3 cm below
      the popliteal fossa crease line) was harvested without delay in every case.
      Primary wound healing of the flap was noted in all patients confirming its
      reliability. Indications and technical hints to ensure successful reconstruction
      are discussed.

PMID- 17452836
TI  - An anatomic study and clinical application of medial pedis flap in Asians.
AB  - Several investigators have reported their clinical experience with medial pedis
      flaps for reconstruction of soft tissue defects of the hand and digits. In a
      cadaveric study in 1997, Jayme and Hamilton described the anatomy of the medial
      branch of the deep division of the medial plantar artery, which is used in the
      medial pedis flap. However, they had only a few cases where this flap was used.
      There have been no such anatomic studies in Korea to date. We found the medial
      pedis flap to be a reliable option for reconstruction of soft tissue defects of
      the hand and digits, based on an anatomic study with 10 dissected fresh cadavers
      (20 cases) and analyzing the clinical outcomes in 17 patients. An anatomic study
      revealed that there were some racial differences in the diameter and length of
      the vessels. The diameter of vessels in the Korean population is larger than that
      in whites. Using a thin, flexible medial pedis flap, which has skin and
      subcutaneous tissue similar to that of the volar aspect of the hand and digits,
      we harvested and performed the reconstruction on 17 patients with soft tissue
      defects of the hands and digits. The vessels used for this flap were the medial
      branch of the deep division of the medial plantar artery and vena comitantes, or
      subcutaneous veins. The mean size of the flap was 2.82 cm x 4.15 cm. All flaps
      were successful without any significant complications. The medial pedis flap
      possesses several advantages: (1) it is very thin in comparison to other standard
      free flaps; (2) it has 2 draining venous pathways; (3) it provides a good color
      and texture match for the hand and fingers; (4) it has a satisfactory recovery of
      protective sensation.

PMID- 17452837
TI  - Prognostic factors in necrotizing fasciitis and myositis: analysis of 16
      consecutive cases at a single institution in Switzerland.
AB  - Necrotizing fasciitis and myositis are life-threatening infections involving the
      superficial fascia and musculature, respectively. Outcome depends on early
      diagnosis and aggressive treatment. Here, we aimed to determine prognostic
      factors for necrotizing soft tissue infections.The medical records of 16
      consecutive patients diagnosed with necrotizing fasciitis (n = 13) and
      necrotizing myositis (n = 3) from 1999 to 2004 were retrospectively reviewed.
      Overall survival was 81.3% for necrotizing soft tissue infections, 84.6% for
      necrotizing fasciitis, and 66.7% for necrotizing myositis. Injection drug use was
      the most common cause of infection (31.3%). Frequent comorbidities were diabetes
      mellitus and hepatitis B and C (25.0%). As infectious agents, group A
      streptococci (GAS) were identified in 10 patients and multiple pathogens in 6
      patients. Lethal outcome was always associated with GAS infection and
      streptococcal toxic shock syndrome (STSS). In our patients, myonecrosis, GAS
      infection, and STSS appeared to be negative prognostic factors for survival in
      necrotizing soft tissue infections.

PMID- 17452838
TI  - Use of the internal mammary vessels as recipient vessels for an omental flap in
      head and neck reconstruction.
AB  - The availability of reliable recipient vessels for free flap transfer in head and
      neck reconstruction may be limited in cases of prior neck dissection or radiation
      therapy. One solution is to use the internal mammary vessels as recipients for a
      free omental flap. Five patients were treated with free omental flap transfer
      using the internal mammary vessels as recipient vessels during head and neck
      reconstruction. Two patients presented with a pharyngocutaneous fistula, 1 had
      mandibular osteomyelitis, 1 had primary esophageal cancer, and 1 had bilateral
      cervical radiation ulcers. All patients had received radiation therapy previously
      (average dose, 75.4 Gy), and 4 had undergone neck dissection (3 bilateral and 1
      ipsilateral). All patients were reconstructed using a free omental flap. Four
      patients had a second free flap combined with the free omental flap (3 free
      jejunal flaps and 1 free fibular osteocutaneous flap). The mean follow-up was
      26.4 months. All free flaps took entirely, the only complication ileus requiring
      reoperation in 1 patient. The internal mammary vessels are reliable recipient
      vessels for a free omental flap in head and neck reconstruction. This procedure
      is a good option for patients in whom previous surgery or radiation therapy has
      compromised local recipient vessels.

PMID- 17452839
TI  - Efficacy of negative pressure therapy to enhance take of 1-stage allodermis and a
      split-thickness graft.
AB  - Negative pressure therapy has been used in various conditions to promote wound
      healing. It has also been used to secure a skin graft by improving
      microcirculation and providing tight adhesion between the graft and the recipient
      bed. The authors coupled the idea of negative pressure therapy for 1-stage
      allodermis and a split-thickness skin graft. This prospective study presents 47
      cases of skin defects treated by 1-stage allodermis and a split-thickness skin
      graft. The patients were divided into 2 groups either treated with simultaneous
      aid of negative pressure therapy for 5 days (group 1, n = 37) or a classic
      tieover dressing (group 2, n = 10). In group 1, 97.8% graft take was noted at day
      5 and the mean time until complete healing was 5.8 days. In group 2, 84% graft
      take was noted at day 5 and mean time until complete healing was 8.9 days with an
      average number of 3.2 dressings. Statistically significant graft take (day 5) and
      time until complete healing was noted (P < 0.05). Good aesthetic and functional
      result mimicking a full-thickness skin graft was achieved in both groups.
      However, frequent dressings, longer time to heal, and more restriction to the
      graft site were needed for group 2. Split-thickness skin added to allodermis
      provided a sufficient amount of dermis to prevent contracture, and the negative
      pressure therapy ensured fast and complete take of the 2-layered composite graft.
      This option can be used to achieve healing mimicking a full-thickness skin graft
      without requiring large full-thickness donor sites.

PMID- 17452840
TI  - The use of bioimpedance analysis to evaluate lymphedema.
AB  - BACKGROUND: Lymphedema, a chronic disfiguring condition resulting from lymphatic
      dysfunction or disruption, can be difficult to accurately diagnose and manage. Of
      particular challenge is identifying the presence of clinically significant limb
      swelling through simple and noninvasive methods. Many historical and currently
      used techniques for documenting differences in limb volume, including volume
      displacement and circumferential measurements, have proven difficult and
      unreliable. Bioimpedance spectroscopy analysis, a technology that uses resistance
      to electrical current in comparing the composition of fluid compartments within
      the body, has been considered as a cost-effective and reproducible alternative
      for evaluating patients with suspected lymphedema. PATIENTS AND METHODS: All
      patients were recruited through the Beth Israel Deaconess Medical Center
      Lymphedema Clinic. A total of 15 patients (mean age: 55.2 years) with upper
      extremity or lower-extremity lymphedema as documented by lymphoscintigraphy
      underwent bioimpedance spectroscopy analysis using an Impedimed SFB7 device.
      Seven healthy medical students and surgical residents (mean age: 26.9 years) were
      selected to serve as normal controls. All study participants underwent analysis
      of both limbs, which allowed participants to act as their own controls. The
      multifrequency bioimpedance device documented impedance values for each limb,
      with lower values correlating with higher levels of accumulated protein-rich
      edematous fluid. RESULTS: The average ratio of impedance to current flow of the
      affected limb to the unaffected limb in lymphedema patients was 0.9 (range: 0.67
      to 1.01). In the control group, the average impedance ratio of the participant's
      dominant limb to their nondominant limb was 0.99 (range: 0.95 to 1.02) (P =
      0.01). CONCLUSIONS: Bioimpedance spectroscopy can be used as a reliable and
      accurate tool for documenting the presence of lymphedema in patients with either
      upper- or lower-extremity swelling. Measurement with the device is quick and
      simple and results are reproducible among patients. Given significant limitations
      with other methods of evaluating lymphedema, the use of bioimpedance analysis may
      aid in the diagnosis of lymphedema and allow for tracking patients over time as
      they proceed with treatment of their disease.

PMID- 17452841
TI  - New technique of total phalloplasty with reinnervated latissimus dorsi
      myocutaneous free flap in female-to-male transsexuals.
AB  - From December 2001 to September 2005, the technique of total penile
      reconstruction with a reinnervated free latissimus dorsi myocutaneous flap was
      used in 22 patients (24-38 years old) with gender dysphoria. These patients were
      followed up for at least 11 months (range, 11-44 months). All flaps survived.
      Complications include hematoma (7 cases), vascular thrombosis (2 cases), partial
      necrosis (1 case), excessive swelling of the neophallus (3 cases), and skin graft
      loss at the donor site (1 case). Of the 19 patients included in the final
      evaluation, the transplanted muscle was able to obtain contraction in 18 (95%)
      cases and 8 patients (42%) had sexual intercourse by contracting the muscle to
      stiffen and move the neopenis. The described technique of neophalloplasty proved
      to be a reliable technique and the muscle movement in the neophallus can be
      expected in almost all cases. The muscle contraction in the neophallus leads to
      "paradox" erection-stiffening, widening, and shortening of the neopenis, which
      allows for sexual intercourse in some patients. Subsequent reconstruction of the
      urethra is possible.

PMID- 17452842
TI  - A randomized, controlled, double-blind study evaluating melanin-encapsulated
      liposomes as a chromophore for laser hair removal of blond, white, and gray hair.
AB  - INTRODUCTION: Laser hair removal of blond and white hair is a complicated task
      with often unsatisfactory results as a result of a lack of laser-absorbing
      chromophore. In the present study, we investigated if repetitive external
      application of liposomal melanin (Lipoxome; Dalton Medicare B.V., Zevenbergschen
      Hoek, The Netherlands) enables removal of blond/white and gray hair with a diode
      laser. METHODS: Forty-two areas of blond, gray, or white facial and body hair of
      16 patients were treated with a liposomal melanin spray (Lipoxome) and 3 cycles
      of 800 nm diode laser at intervals of 8 weeks (28-40 J/cm). A control group of 16
      patients applied physiological saline spray before diode laser treatment. Hair
      regrowth was measured 8 weeks after each cycle and additionally 6 months after
      the last treatment by counting the number of terminal hairs compared with
      baseline pretreatment values. Complications and treatment outcomes were
      documented. RESULTS: Mean regrowth in the liposomal melanin group was 83% after 3
      treatment cycles. Six months after therapy, average terminal hair count compared
      with baseline pretreatment showed 14% reduction. Although significant difference
      was seen compared with the control group showing a 10% reduction of hair growth
      after 6 months (P < 0.05), the clinical outcome was disappointing. CONCLUSIONS:
      Melanin-encapsulated liposomal spray in combination with diode laser treatment
      showed significant higher efficacy in the treatment of white and blond hair
      compared with a control group. However, the clinically observed hair reduction
      was so weak that additional effort as well as higher costs argues against the
      application of the tested formulation.

PMID- 17452843
TI  - V.A.C. Therapy normalizes vascular response of injured tissue in full-thickness
      wounds in rabbits.
AB  - V.A.C. Therapy applied to a cutaneous wound was hypothesized to alter vascular
      regulation in underlying tissue. Two full-thickness wounds were created on the
      dorsum of 7 New Zealand albino rabbits. One site was treated with V.A.C. Therapy;
      the other, with saline-moistened gauze. Local perfusion levels in the muscle were
      measured using laser Doppler flowmetry. Using vena caval occlusion, blood
      pressure was decreased progressively from baseline under vasonormal conditions
      and during systemic infusion of a vasodilator and a vasoconstrictor. The pressure
      flow relationships for the carotid and V.A.C. Therapy-treated wound sites showed
      3 distinct curves, with vasodilator curves shifted upwards and vasoconstrictor
      curves downwards relative to vasonormal curves (P < 0.05). By contrast,
      vasodilator curves in the saline-gauze treated sites were indistinguishable from
      vasonormal curves. Thus, in a rabbit model, application of V.A.C. Therapy to
      cutaneous wounds normalized the vascular response to vasoactive drugs in a manner
      similar to undisturbed carotid circulation.

PMID- 17452844
TI  - Combined bone allograft and adipose-derived stem cell autograft in a rabbit
      model.
AB  - Currently available options for the repair of bony defects have substantial
      limitations. Much work has looked to the possibility of engineering bone using
      stem cells. These tissue-engineering efforts have focused on calvarial defect
      models, which have the advantages of minimal load-bearing and a large surface
      area. This study aims to solve the somewhat more challenging problem of repairing
      segmental bony defects such as those of the mandible and long bones. Four groups
      of decellularized bone tubes with cortical perforations were implanted
      subcutaneously in a rabbit model: empty bone tubes, bone tubes containing fibrin
      glue alone, bone tubes containing fibrin glue and freshly isolated autologous
      adipose-derived stem cells (ASCs), and bone tubes containing fibrin glue and
      predifferentiated autologous ASCs. Results showed a foreign body response
      characterized by fibrous capsule formation with minimal angiogenesis and no
      evidence of osteoblastic activity. Substantial changes are needed if this model
      is to become viable.

PMID- 17452845
TI  - Comparison of various methods and materials for treatment of skin laceration by a
      3-dimensional measuring technique in a pig experiment.
AB  - BACKGROUND: The ability to obtain an objective comparison of scar formations by
      reproducible and quantitatively measurable results have posed a longstanding
      problem. This was especially troublesome when conclusions were to be drawn about
      the materials and methods applied. Two-dimensional methods (photography) gave no
      plastic impression about the spatial coherences in an examined scar. However, a
      quantifiable and reproducible recording of volumes and a 3-dimesional
      visualization of scars should provide the basis of any evaluation of methods and
      materials. METHODS: The OPTOCAT 3-dimensional scanning technique that was used
      was provided by the Breuckmann GmbH Company (Meersburg, Germany), and it permits
      a 3-dimensional, contact-free recording of data. The experiment animal was the
      Goettinger minipig. A total of 10 animals were used to examine the process of
      wound healing and scar development in full skin incisions. Every animal was
      incised 20 times with a 10-cm long and 20 times with a 2-cm long wound. In our
      investigation, comparable suture materials (skin adhesive, absorbing and
      nonabsorbing suture materials) of the companies Braun (Histaocryl, Monosyn,
      Safil, Premilene) and Ethicon (Dermabond, Monocryl, Vicryl, Prolene) as well as
      various suture techniques were used (continuous, mattress suture, and over-and
      over/interrupted suture; each once with and once without an intracutaneous
      suture). In the course of the trial, numerous images of all wounds-a total 1200
      were taken. Thanks to the 3-dimensional software, the resulting scar volumes of
      lacerations, which received different wound management, were quantifiably
      recorded, compared, and evaluated. RESULTS: In total, dehiscence occurred in 2.5%
      of all treated wounds. The greatest share (15%) fell to wounds treated with
      Histoacryl skin adhesive. In the end, skin adhesive, mattress, and interrupted
      suture all delivered similar results. An additional intracutaneous suture had,
      with an increasing wound length, a positive effect on the intention/wound
      healing, especially in connection with the application of skin adhesive. Except
      the combination of continuous absorbable suture and intracutaneous suture, the
      scar volume dwindled over time and adapted to the surrounding skin level.
      Continuous sutures were, by comparison, more inclined to an increased scarring
      (absorbable suture > nonabsorbable suture). It did not escape our notice that in
      case of small wounds, all various suturing materials and methods led to almost
      identical results. With respect to scarring, no significant difference regarding
      the suturing material was proven. CONCLUSIONS: If possible, the wound closure,
      treated with common suturing techniques and especially with skin adhesive, should
      be enhanced by an intracutaneous suture with an increasing length of the wound.
      Under certain circumstances, skin adhesive is an adequate substitute for common
      suturing materials and methods. The final decision about the method and material
      is as much closely related to the length and localization of the wound as to time
      exposure, efficiency, and the comfort of the patient. SUMMARY: For objective
      comparison of intention and scarring, a scanning technique was used that permits
      a quantifiable, contact-free, single-session recording of volume differences. For
      this purpose, various suture materials and methods were used. Altogether, it
      could be shown that, if possible, wound closure treated with common suturing
      techniques, and especially with skin adhesive, should be enhanced by an
      intracutaneous suture with an increase in wound length. At the same time and
      under certain circumstances, skin adhesive poses an adequate substitute for the
      common suturing materials and methods. In the end, however, the final decision
      about the choice of method and material should be made depending on the
      localization and expanse of the wound as well as on the comfort of the patient
      (eg, absorbable suture/nonabsorbable suture), the time of exposure (eg, skin
      adhesive vs suture), and the economic efficiency (eg, producer of suture
      material).

PMID- 17452846
TI  - Securing skin grafts to microvascular free flaps using the vacuum-assisted
      closure (VAC) device.
AB  - We performed microvascular free muscle flaps on 5 patients using the vacuum
      assisted closure (VAC) device (KCI, San Antonio, TX) to secure a split-thickness
      skin graft to the external surface of the flap in each case. This method of skin
      graft fixation was selected in each case because of the complex 3-dimensional
      shape of the flap or because of concerns of inadequate fixation provided by
      conventional tie-over bolster techniques in regions that experience a significant
      amount of shear stress. All 5 flaps remained viable throughout the treatment
      course and all 5 patients experienced excellent skin-graft take. Also, decreased
      edema was noted in all 5 flaps. We conclude that the VAC device is a useful tool
      in the fixation of skin grafts to microvascular free flaps and that its use does
      not compromise free-flap viability.

PMID- 17452847
TI  - Frontalis slings with palmaris tendon as an adjuvant treatment for myasthenic
      blepharoptosis: a case report.
AB  - Ocular myasthenia (OMG) is a special form of general myasthenia gravis (MG),
      characterized by unilateral or bilateral ptosis. Although medical management
      remains the first line of therapy for the ocular manifestations of MG, the
      limitations of anticholinesterases and immunosuppressive therapy are well
      documented. We report one patient who did not achieve symptom control with
      medical therapy. The ptosis was corrected alternatively by bilateral frontalis
      slings with autogenous palmaris longus (PL) tendon. The eyelids were in good
      position 12 months postoperatively, with good eyelid closure. The surgical result
      has been stable for more than 2 years. For patients who have failed to respond to
      medical therapy for MG, frontalis sling procedure is an appropriate adjuvant
      treatment option.

PMID- 17452848
TI  - The sandwich design: a new method to close a high-output enterocutaneous fistula
      and an associated abdominal wall defect.
AB  - Fistulas draining through large abdominal wall defects are exceptionally
      difficult to treat and are associated with a very high mortality. This case
      report describes a new method for closure of these fistulas where prior
      conservative and surgical treatment had failed. Initial use of a vacuum-assisted
      closure (VAC) system optimized wound care and led to coverage of the exposed
      intestines with granulation tissue. The serratus muscle of a composite free
      latissimus dorsi-serratus flap was used to close the fistula, while the large
      abdominal wall defect was closed with the musculocutaneous latissimus dorsi flap.
      Temporary placement of a VAC system between the serratus muscle and the
      latissimus dorsi muscle immobilized the serratus to the fistula and counteracted
      changes in abdominal pressure. The layering of muscle, VAC system, and muscle
      resembles a sandwich. The advantage of the sandwich design is an extraperitoneal
      approach that provides tension-free closure of the fistula and abdominal wall,
      with well-vascularized tissue.

PMID- 17452849
TI  - The use of reinforced adhesive tape in supporting pendulous upper eyelid lesions.
AB  - Prolonged interference in the conjugate vision of an infant by monocular
      occlusion of the visual axis produces a significant risk of the development of
      stimulus deprivation amblyopia. Any clinician dealing with a large number of
      children's vascular lesions in the periorbital region will encounter cases where
      vision is threatened in this way. We have used a simple technique to help avoid
      interference with the visual axis while awaiting responses to conventional
      treatments of vascular lesions including laser and more rarely systemic steroid
      therapy. This involves the use of a reinforced adhesive tape.

PMID- 17452852
TI  - A mastopexy with lateral intercostal artery perforator (LICAP) flaps for patients
      after massive weight loss.

PMID- 17452854
TI  - Basal cell carcinoma and therapeutic radiation in childhood: methodological
      issues.

PMID- 17452856
TI  - Comment on "Closure of massive abdominal wall defects: a case report using the
      abdominal reapproximation anchor (ABRA) system".

PMID- 17452857
TI  - Microsurgery training on omentum: pickled vessels.

PMID- 17452858
TI  - Efficient dissection of an intramuscular perforator using bipolar forceps.

PMID- 17452859
TI  - Late artecoll granulomas aggravated by pregnancy.

PMID- 17452860
TI  - Low-dose oral propranolol could reduce brown adipose tissue F-18 FDG uptake in
      patients undergoing PET scans.
AB  - Fluorine-18 fluoro-2-deoxy-D-glucose (FDG) uptake in brown adipose tissue (BAT)
      may generate FDG-PET scan misinterpretation. Recent studies have shown reduced
      FDG uptake in BAT in rats treated with high doses of the beta-blocker
      propranolol. The aim of this observational study was to present a cohort of
      patients with high FDG uptake in BAT who underwent a second scan after receiving
      a low dose of propranolol, to determine whether the use of this premedication
      could improve the diagnostic confidence of FDG-PET scans by inhibition FDG uptake
      in BAT, and also whether administration of this drug affects tracer uptake in
      tumors. METHODS: Twenty-six cancer patients, presenting with increased BAT FDG
      uptake, were selected prospectively. On a different day, patients were given
      propranolol 20 mg orally 60 minutes prior to FDG administration 185-277.5 MBq (5
      7.5 mCi) and were scanned again. Basal and postpropranolol BAT SUVmax, and tumor
      SUVmax (when present) were measured. RESULTS: Mean basal BAT SUVmax was 5.52+/
      2.3. Mean postpropranolol SUVmax was 1.39+/-0.42 (P<0.0001). In 11 patients, the
      basal mean tumor SUVmax was 8.07+/-6.4, and 7.88+/-5.9 in postpropranolol scans
      (P=0.53). Nine patients showed mediastinal FDG uptake in the basal scan,
      affecting image interpretation. This was not observed in postpropranolol scans.
      No adverse effects due to propranolol were encountered. CONCLUSIONS: In this
      patient cohort, there was significant reduction of FDG uptake in BAT following
      propranolol administration, allowing for adequate interpretation of FDG-PET and
      software-fused FDG-PET with CT images, particularly in the mediastinal area,
      without affecting tumor tracer uptake.

PMID- 17452861
TI  - Radioguided parathyroidectomy for recurrent parathyroid cancer.
AB  - We report a case of radioguided parathyroidectomy in a patient with parathyroid
      carcinoma. A 61-year-old woman presented to our center with persistent
      hypercalcemia (17.2 mg/dL) and hyperparathyroidism (PTH=324 pg/mL) following her
      second neck resection for recurrent parathyroid carcinoma at an outside facility.
      Her elevated serum calcium had not responded to treatment with intravenous
      bisphosphonates, furosemide, or calcitonin. Calcimemetic therapy (Cinacalcet) was
      effective but had to be discontinued due to GI intolerance. She requested a
      second opinion at our center after being referred for palliative radiation
      therapy for presumed inoperable disease. On presentation, she remained
      symptomatic with bone and joint pain, diffuse abdominal pain and fatigue. Repeat
      technetium-99m sestamibi (Tc-99m sestamibi) scintigraphy showed a faint area of
      uptake near the right clavicular head, adjacent to the site of her previous
      resections. With the intraoperative guidance of a hand-held gamma probe, a 2 cm
      recurrent parathyroid carcinoma was located and successfully excised.
      Intraoperative PTH levels confirmed surgical cure of this previously undetected
      foci of disease. The use of radioguidance and intraoperative PTH monitoring were
      the keys to a successful resection, and our patient remains disease free with 17
      months of follow-up.

PMID- 17452862
TI  - F-18 FDG PET demonstration of a thyroid metastasis in a patient with colon
      cancer.
AB  - A 51-year-old man with a history of surgical removal of sigmoid colon cancer
      underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to
      search for distant metastases and/or local recurrence because the
      carcinoembryonic antigen level was elevated. F-18 FDG PET images showed increased
      focal FDG uptake in the left lobe of the thyroid. Computed tomography images
      showed thyroid tumor in the left lobe as well as F-18 FDG PET images. Thereafter
      he underwent thyroidectomy and the resected specimen was histopathlogically shown
      to have thyroid metastasis from colon cancer. F-18 FDG PET was useful to detect
      thyroid metastasis from colon cancer as well as the most frequently seen
      metastatic sites such as liver, lungs, and lymph nodes.

PMID- 17452863
TI  - Role of salivary gland scintigraphy with Tc-99m pertechnetate in determining
      treatment of solitary parotid gland tumors: a retrospective study.
AB  - PURPOSE OF THE REPORT: Although salivary gland scintigraphy has been useful for
      the diagnosis of Warthin's tumor (WT), there are no reports concerning the
      clinical impact of this scintigraphy. MATERIALS AND METHODS: We retrospectively
      investigated 127 patients with solitary parotid tumors who had undergone salivary
      gland scintigraphy. RESULTS: For patients who had surgery, the sensitivity,
      specificity, and accuracy of differentiating WT from non-WTs were 95%, 91%, and
      92%, respectively. There was a significant correlation between scintigraphic
      results and the treatment decisions made for the 127 patients (chi2=16.5,
      P=0.00026). The proportion of WT patients among those who underwent surgery was
      19%, whereas 42% of those who were suspected to have WT from scintigraphy were
      followed without surgical intervention. The main reasons for clinical observation
      in these patients were comorbidity, refusal of surgery, and age. CONCLUSIONS: The
      high percentage of nonsurgical patients suspected to have WT can be explained by
      the high diagnostic accuracy of salivary gland scintigraphy, which is useful for
      determining further management when surgery is contraindicated or is refused by
      the patient.

PMID- 17452864
TI  - Tc-99m ciprofloxacin scans for detection of tubercular bone infection.
AB  - Tc-99m MDP and Tc-99m ciprofloxacin scans were performed in 14 patients with
      suspected tubercular bone disease and in 2 cases of nontubercular bone infection.
      In 5 patients the findings were true negative. There were no false positives and
      1 was false negative. The sensitivity, specificity, and positive predictive value
      were found to be 93, 71, and 87.5%, respectively, for detection of bone
      tubercular lesions. However, the test does not distinguish TB osteomyelitis from
      other types of osteomyelitis. Delayed 24 hour scans were found useful to
      differentiate between inflammatory and infective lesions. The aim of this study
      was to evaluate the usefulness of the Tc-99m ciprofloxacin scan as a means to
      detect tubercular bone disease.

PMID- 17452865
TI  - Concordant F-18 FDG PET and Y-90 Bremsstrahlung scans depict selective delivery
      of Y-90-microspheres to liver tumors: confirmation with histopathology.
AB  - Selective Internal Radiation Therapy using yttrium-90 (Y-90) microspheres is a
      novel method for the treatment of advanced liver cancer. The procedure involves
      intrahepatic arterial delivery of the Y-90 microspheres. Since hepatic tumors
      derive their blood supply mainly from the hepatic arteries, it is assumed that
      the microspheres will be preferentially delivered to tumor cells. However, this
      has not been confirmed at histology. We report a case of hepatic metastasis from
      an unknown primary, where treatment with Y-90 microspheres was the only available
      option due to inoperability and low tolerance to chemotherapy. Pretherapy F-18
      FDG-PET scan defined the distribution of the active tumor within the liver.
      Following the injection of Y-90 microspheres, Bremsstrahlung imaging showed
      uptake only in the F-18 FDG-PET-defined tumor area. Post therapy debulking
      surgery was performed and histopathology of tumor samples confirmed the
      preferential distribution of the injected microspheres in the hepatic tumor
      circulation with very little in the healthy liver tissue. The case confirms the
      preferential blood flow to hepatic tumors as depicted by the distribution of Y-90
      microspheres injected directly in the hepatic arteries. It also demonstrates that
      concordance between F-18 FDG-PET and Y-90 Bremsstrahlung scans can be a useful
      clue to the in vivo distribution of microspheres.

PMID- 17452866
TI  - Timing of iodine-123 scintigraphy following use of recombinant human thyrotropin
      in differentiated thyroid carcinoma.

PMID- 17452867
TI  - Thyroid C-cell hyperplasia shown by combined In-111 pentetreotide, Tc-99m
      pertechnetate, and Tc-99m MIBI scintigraphy.

PMID- 17452868
TI  - Benign struma ovarii in a patient with invasive papillary thyroid cancer:
      detection with I-131 SPECT-CT.

PMID- 17452869
TI  - FDG uptake in metastatic spreading mucoepidermoid carcinoma of the thyroid.

PMID- 17452870
TI  - Metastatic malignant melanoma to the thyroid gland detected by FDG-PET imaging.

PMID- 17452871
TI  - Laryngeal giant cell tumor mimicking thyroid cancer demonstrated by PET/CT.

PMID- 17452872
TI  - Atrial metastasis of esophageal carcinoma detected by follow-up FDG PET/CT.

PMID- 17452873
TI  - Visualization of contralateral axillary sentinel node in breast cancer in a
      patient with a history of sternotomy.

PMID- 17452874
TI  - Paraneoplastic ACTH secretion: bronchial carcinoid overlooked by planar indium
      111 pentetreotide scintigraphy and accurately localized by SPECT/CT acquisition.

PMID- 17452875
TI  - F-18-FDG-PET/CT leads to diagnosis of cryptococcal pneumonia where recurrent
      metastatic rhabdomyosarcoma was suspected.

PMID- 17452876
TI  - Gated myocardial perfusion SPECT in patients with a small heart: effect of
      zooming and filtering.

PMID- 17452877
TI  - Avid FDG uptake in the right ventricle coupled with enhanced intercostal muscle
      hypermetabolism in pneumoconiosis.

PMID- 17452878
TI  - Misdiagnosis of multiple bone metastases due to increased FDG uptake in
      polyostotic fibrous dysplasia.

PMID- 17452879
TI  - Additional benefit of SPECT/CT in bone scanning of metastatic renal cell
      carcinoma.

PMID- 17452880
TI  - PET monitoring of clear cell sarcoma of tendons and aponeuroses.

PMID- 17452882
TI  - Current readings in nuclear medicine.

PMID- 17452881
TI  - An unusual presentation of abdominal aortic aneurysm on static renal Tc-99m DMSA
      scintigraphy.

PMID- 17452883
TI  - Epigenetics--a science of heritable biological adaptation.

PMID- 17452884
TI  - Registry of randomized controlled trials in transplantation: January 1 to June
      30, 2006.

PMID- 17452888
TI  - Can old be too old for kidney transplantation?

PMID- 17452889
TI  - Cardiac statins more than just lipid busters.

PMID- 17452890
TI  - Isolation of large numbers of mesenchymal stem cells from the washings of bone
      marrow collection bags: characterization of fresh mesenchymal stem cells.
AB  - BACKGROUND: Bone marrow (BM) is an excellent source of mesenchymal stem cells
      (MSC) which can be expanded in vitro for further use. However, large volumes of
      BM specimens are not routinely available. We hypothesized that the normally
      discarded BM collection kits might be a convenient source of large numbers of
      MSC. METHODS: Marrow specimens were isolated from used Fenwal collection kits.
      Purified mononuclear cells (MNC) were screened by multiparameter flow cytometry
      to identify MSC, which were later expanded by in vitro culture. Immunophenotyping
      and differentiation assays were performed initially and at subculture. Both fresh
      and frozen BM were tested. RESULTS: An average of 9.62E+08 MNC were collected. In
      this, a cell population was identified that was CD44+, CD73+, CD90+ and CD105+,
      but negative for hematopoietic markers. This population represented on average
      0.015% of the total BM MNC fraction, or on average 1 in 6,666 MNC. The population
      was considered to be MSC based on its immunophenotype profile, suppressive
      ability in mixed lymphocyte cultures, morphology, and ability to differentiate
      into bone and fat cells. CONCLUSIONS: This study demonstrates that large numbers
      of MSC can be obtained from the normally discarded collection devices following
      harvest of BM for clinical transplant. This novel method offers potential for
      obtaining large numbers of MSC for potential therapeutic or investigational
      purposes following their in vitro expansion.

PMID- 17452891
TI  - Diabetic complications associated with new-onset diabetes mellitus in renal
      transplant recipients.
AB  - BACKGROUND: Data are scarce regarding the incidence and risk factors for
      complications of new-onset diabetes mellitus (NODM) in renal transplant patients.
      METHODS: United States Renal Data System (USRDS) data from primary renal
      transplant recipients during 1995-2001 who developed NODM was used to examine
      diabetic complications over the first three years posttransplant. Prognostic
      models were used to evaluate patient characteristics and treatment choices
      associated with risk of each class of complications. Propensity scores for choice
      of calcineurin inhibitor were included in multivariate analyses. RESULTS: The
      analysis included 21,489 patients, of whom 4,105 developed NODM by 3 years
      posttransplant. One or more NODM complications developed in 2,393 patients (58.3%
      of all patients with NODM), comprising ketoacidosis (334, 8.1%), hyperosmolarity
      (131, 3.2%), renal complications (1,286, 31.3%), ophthalmic complications (340,
      8.3%), neurological complications (665, 16.2%), peripheral circulatory disorders
      (170, 4.1%) and hypoglycemia/shock (301, 7.3%). Complications developed within a
      mean of 500 to 600 days from diagnosis of NODM. Multivariate analysis showed that
      increased recipient age, higher body mass index, African-American race, hepatitis
      C infection, hypertension as cause of end-stage renal disease, cold ischemia
      >or=30 hours, and use of tacrolimus each increased risk of complications.
      CONCLUSION: NODM is associated with similar complications to those seen in the
      general population, but these appear to develop at an accelerated rate. Obesity
      and use of tacrolimus are the only modifiable factors that appear to affect risk
      of NODM or its complications.

PMID- 17452892
TI  - Evaluation of hepatocyte growth factor as a sensitive marker for early detection
      of acute renal allograft rejection.
AB  - BACKGROUND: It has been shown that hepatocyte growth factor (HGF), besides its
      well-established hepatotrophic effect in liver regeneration, is involved in the
      regeneration of the kidney after injury. In the present study we investigated
      whether HGF can serve as a marker for detection of acute rejection in the early
      posttransplantation period. METHODS: HGF levels were determined in pre- and
      posttransplant sera (up to day 21) of 26 recipients with biopsy-proven acute
      rejection, 30 recipients with acute tubular necrosis (ATN), and 32 recipients
      without posttransplant complications. RESULTS: Although no association was found
      between pretransplant HGF and death-censored functional graft survival, receiver
      operating characteristic (ROC) curves demonstrated that HGF measured during the
      entire posttransplant study period, and especially on days 3 to 5, was a good
      marker for differentiating recipients who subsequently developed acute rejection
      from recipients with an uncomplicated course (P<0.0001, specificity 87%,
      sensitivity 84%). HGF measured from day 3 until day 21 posttransplantation, and
      especially on days 7 to 9, was also a sensitive marker for differentiating
      recipients with ATN from recipients with an uncomplicated course (P<0.0001). If
      considered in combination with sCD30, the diagnostic value of HGF was further
      improved. While 73% of samples from patients with impending rejection were
      positive for both HGF and sCD30, 94% of samples from nonrejecting patients were
      double-negative and none of the samples from this group fell into the double
      positive category (P<0.0001). CONCLUSIONS: Our data suggest that HGF measured
      during the early posttransplant period might be a useful parameter for early
      detection of acute renal allograft rejection.

PMID- 17452893
TI  - Maintenance immunosuppression with mycophenolate mofetil and corticosteroids in
      pediatric kidney transplantation: temporary benefit but not without risk.
AB  - BACKGROUND: Aiming at reducing cyclosporine toxicity, we investigated safety and
      efficacy of mycophenolate mofetil (MMF) as an immunosuppressive drug in pediatric
      kidney transplantation compared with cyclosporine (CsA), both in combination with
      corticosteroids. METHODS: One year after kidney transplantation, children on
      triple immunosuppression, having experienced no more than one, steroid-sensitive,
      acute rejection episode, were randomized to withdrawal of either CsA or MMF and
      were followed for 2 yr. RESULTS: In each group, two patients had an acute
      rejection episode during withdrawal. Treatment failure occurred in 3 of 21 MMF
      and 5 of 23 CsA patients. Final analysis was for 18 patients in either group. A
      larger than 10 mL/min 1.73 m decrease in glomerular filtration rate was observed
      in more patients on CsA than on MMF (73% vs. 29%, P=0.019). No differences in
      blood pressure or nightly decrease of blood pressure were noted.
      Hypercholesterolism improved in the MMF (-16%), but not the CsA group (+5%,
      P<0.05), over the first, but not over both study years. Differences in
      triglycerid levels between groups were not shown. At study end, MMF patients
      tended to have lower hemoglobin levels than patients on CsA. Two MMF patients
      experienced a first acute rejection episode during the second study year,
      resulting in chronic transplant glomerulopathy with graft loss in one and
      deterioration of kidney function in the other. CONCLUSION: In pediatric kidney
      transplantation, maintenance immunosuppression with MMF together with
      corticosteroids has short-term benefits for kidney function and lipid pattern
      compared with CsA but is not without risk of complications.

PMID- 17452894
TI  - Gene-expression profiles and age of donor kidney biopsies obtained before
      transplantation distinguish medium term graft function.
AB  - BACKGROUND: Donor factors such as age profoundly influence long-term graft
      function after cadaveric renal transplantation, but the molecular signature of
      these aspects in the allograft remains unknown. METHODS: We analyzed the genome
      wide gene expression signature of donor kidney biopsies of different ages
      obtained before transplantation. Subsequent analysis compared expression profiles
      from allografts with excellent function versus impaired function at 1 yr after
      engraftment. Differential expression profiles were analyzed on the level of
      molecular function and biologic role, as well as by analysis of co-regulation
      through transcription factors, regulatory networks, and protein-protein
      interaction data utilizing extended bioinformatics. RESULTS: The 15 subjects with
      excellent transplant function defined as calculated GFR>or=45 mL/min/1.73 m2 at 1
      yr exhibited a distinctly different gene expression profile than the matched 16
      subjects with impaired function defined as calculated GFR<45 mL/min/1.73 m2.
      Donor kidneys from recipients with impaired allograft function showed activation
      of genes mainly belonging to the functional classes of immunity, signal
      transduction, and oxidative stress response. Two-thirds of these genes exhibited
      at least one protein interacting partner, suggesting choreographed intracellular
      events differentiating the two recipient groups. However, donor age may have
      confounded some of the associations found between gene profiles and graft
      function. CONCLUSION: In summary, a distinctive gene expression profile in the
      donor kidney at transplantation together with donor age predicts medium term
      allograft function in recipients of cadaveric allografts.

PMID- 17452895
TI  - No association of factor V Leiden, prothrombin G20210A, and MTHFR C677T gene
      polymorphisms with kidney allograft survival: a multicenter study.
AB  - BACKGROUND: It has been proposed that inherited risk factors of venous
      thromboembolism, such as factor V G1691A (FV-Leiden), prothrombin G20210A, and
      methylenetetrahydrofolate reductase (MTHFR) C677T, might be associated with
      poorer survival rates of transplanted kidneys. On the basis of this hypothesis,
      we performed a multicenter study, involving recipients of primary and repeat
      kidney transplants, to investigate the potential effect of these three single
      nucleotide polymorphisms (SNP) on graft survival. METHODS: The study consisted of
      676 first and 651 retransplant patients. Using the polymerase chain reaction
      sequence specific primers method, we typed all patients for the three SNP and
      analyzed graft survival. RESULTS: We could not find a statistically significant
      association between graft survival and factor V Leiden or MTHFR C677T genotypes.
      A better 3-yr graft survival was found for first transplant recipients with the
      genotype prothrombin 20210 G/G as compared to those with the G/A genotype
      (P=0.031). However, Bonferroni correction for the three SNPs investigated in this
      series rendered the P value insignificant (P(corrected)=0.093). CONCLUSION: We
      did not find a statistically significant association of SNP factor V Leiden
      G1691A and MTHFR C677T with renal graft survival. Prothrombin G20210A resulted in
      a significant association that was not sustained after Bonferroni correction.
      This SNP might be an interesting candidate for future studies.

PMID- 17452896
TI  - The functional, metabolic, and anabolic responses to exercise training in renal
      transplant and hemodialysis patients.
AB  - BACKGROUND: Exercise intolerance is common in hemodialysis (HD) and renal
      transplant (RTx) patients and is related to muscle weakness. Its pathogenesis may
      vary between these groups leading to a different response to exercise. The aim of
      the study was to compare intrinsic muscular parameters between HD and RTx
      patients and controls, and to assess the response to exercise training on
      exercise capacity and muscular structure and function in these groups. METHODS:
      Quadriceps function (isokinetic dynamometry), body composition (dual-energy x-ray
      absorptiometry), and vastus lateralis muscle biopsies were analyzed before and
      after a 12-week lasting training-program in 35 RTx patients, 16 HD patients, and
      21 healthy controls. RESULTS: At baseline, myosin heavy chain (MyHC) isoform
      composition and enzyme activities were not different between the groups. VO2peak
      and muscle strength improved significantly and comparably over the training
      period in RTx, HD patients and controls (p(time)<0.05). The proportion of MyHC
      type I isoforms decreased (p(time)<0.001) and type IIa MyHC isoforms increased
      (p(time)<0.05). The 3-hydroxyacyl-CoA-dehydrogenase activity increased
      (p(time)=0.052). Intrinsic muscular changes were not significantly different
      between groups. In the HD group, changes in lean body mass were significantly
      related to changes in muscle insulin-like growth factor (IGF)-II and IGF binding
      protein-3. CONCLUSIONS: Abnormalities in metabolic enzyme activities or muscle
      fiber redistribution do not appear to be involved in muscle dysfunction in RTx
      and HD patients. Exercise training has comparable beneficial effects on
      functional and intrinsic muscular parameters in RTx patients, HD patients, and
      controls. In HD patients, the anabolic response to exercise training is related
      to changes in the muscle IGF system.

PMID- 17452897
TI  - Renal transplantation in elderly patients older than 70 years of age: results
      from the Scientific Registry of Transplant Recipients.
AB  - BACKGROUND: Elderly patients (ages 70 yr and older) are among the fastest-growing
      group starting renal-replacement therapy in the United States. The outcomes of
      elderly patients who receive a kidney transplant have not been well studied
      compared with those of their peers on the waiting list. METHODS: Using the
      Scientific Registry of Transplant Recipients, we analyzed data from 5667 elderly
      renal transplant candidates who initially were wait-listed from January 1, 1990
      to December 31, 2004. Of these candidates, 2078 received a deceased donor
      transplant, and 360 received a living donor transplant by 31 December 2005. Time
      to-death was studied using Cox regression models with transplant as a time
      dependent covariate. Mortality hazard ratios (RRs) of transplant versus waiting
      list were adjusted for recipient age, sex, race, ethnicity, blood type, panel
      reactive antibody, year of placement on the waiting list, dialysis modality,
      comorbidities, donation service area, and time from first dialysis to first
      placement on the waiting list. RESULTS: Elderly transplant recipients had a 41%
      lower overall risk of death compared with wait-listed candidates (RR=0.59;
      P<0.0001). Recipients of nonstandard, that is, expanded criteria donor, kidneys
      also had a significantly lower mortality risk (RR=0.75; P<0.0001). Elderly
      patients with diabetes and those with hypertension as a cause of end-stage renal
      disease also experienced a large benefit. CONCLUSIONS: Transplantation offers a
      significant reduction in mortality compared with dialysis in the wait-listed
      elderly population with end-stage renal disease.

PMID- 17452898
TI  - Transfer of allograft specific tolerance requires CD4+CD25+T cells but not
      interleukin-4 or transforming growth factor-beta and cannot induce tolerance to
      linked antigens.
AB  - BACKGROUND: The mechanisms by which CD4+T cells, especially CD4+ CD25+T cells,
      transfer allograft specific tolerance are poorly defined. The role of cytokines
      and the effect on antigen-presenting cells is not resolved. METHODS: Anti-CD3
      monoclonal antibody (mAb) therapy induced tolerance to PVG heterotopic cardiac
      transplantation in DA rats. Peripheral CD4+T cells or CD4+ CD25+ and CD4+ CD25-T
      cell subsets were adoptively transferred to irradiated DA hosts grafted with PVG
      heart grafts. For specificity studies, tolerant CD4+T cells were transferred to
      hosts with Lewis or (PVGxLewis)F1 heart grafts. Cytokine mRNA induction and the
      requirement for interleukin (IL)-4 and transforming growth factor (TGF)-beta in
      the transfer of tolerance was assessed. RESULTS: CD4+T cells transferred specific
      tolerance and suppressed naive CD4+T cells capacity to effect rejection of PVG
      but not Lewis grafts. (PVGxLewis)F1 grafts had a major rejection episode but
      recovered. Later these hosts accepted PVG but not Lewis skin grafts. Adoptive
      hosts restored with tolerant or naive cells had similar levels of mRNA expression
      for all Th1 and Th2 cytokines and effector molecules assayed. Transfer of
      tolerance by CD4+T cells was not blocked by mAb to IL-4 or TGF-beta. CD4+ CD25-T
      cells from either naive or tolerant hosts effected rejection. In contrast neither
      tolerant nor naive CD4+ CD25+T cells restored rejection. CONCLUSIONS: Specific
      tolerance transfer required CD4+ containing CD4+ CD25+T cells. An inflammatory
      response with induction of mRNA for Th1 and Th2 cytokines plus cytotoxic effector
      molecules occurred, but IL-4 and TGF-beta were not essential. Inhibition of
      antigen presenting cells was not the sole mechanism as there was no linked
      tolerance.

PMID- 17452899
TI  - Successful islet transplantation to two recipients from a single donor by
      targeting proinflammatory cytokines in mice.
AB  - BACKGROUND: Currently, the inability to achieve successful islet transplantation
      from one donor to one recipient is a major obstacle facing clinical islet
      transplantation. We herein determined whether this limitation could be overcome
      by targeting pro-inflammatory cytokines with the prevention of immediate islet
      graft loss in association with engraftment in mice. METHODS: Isolated islets were
      grafted into the liver of streptozotocin-induced diabetic mice and the role of
      proinflammatory cytokines in the engraftment of islets was evaluated with the use
      of interferon (IFN)-gamma-/- mice and monoclonal antibodies against
      proinflammatory cytokines. RESULTS: Hyperglycemia in streptozotocin-induced
      diabetic mice receiving 200 syngenic islets, which were isolated from a single
      mouse pancreas, was ameliorated when IFN-gamma-/-, but not wild-type mice, were
      used as recipients. The treatment with anti-IFN-gamma antibody produced
      normoglycemia in diabetic wild-type mice receiving 200, but not 100 islets.
      However, when anti-tumor necrosis factor-alpha and anti-interleukin-1beta
      antibodies were administered in conjunction with anti-IFN-gamma antibody, wild
      type diabetic mice receiving 100 islets became normoglycemic after
      transplantation. In addition, the favorable effect of the combined use of
      antibodies was similarly achieved in mice receiving islet allografts when
      rejection was prevented with anti-CD4 antibody treatment. CONCLUSIONS: These
      findings clearly demonstrate that successful islet transplantation from one donor
      to two recipients is feasible by targeting pro-inflammatory cytokines in mice,
      thus suggesting a potential application in clinical islet transplantation if
      similar mechanisms of islet graft loss could be mediated in humans.

PMID- 17452900
TI  - Pitavastatin suppresses acute and chronic rejection in murine cardiac allografts.
AB  - INTRODUCTION: HMG-CoA reductase inhibitors play several roles in the maintenance
      of organ transplants. We investigated the role of pitavastatin, a potent and
      newly developed HMG-CoA reductase inhibitor, in cardiac allograft rejection and
      mechanism of graft arterial disease (GAD) suppression. METHODS: Balb/c mice
      hearts were transplanted into C3H/He mice (a full allomismatch combination) to
      assess acute rejection or C57BL/6 hearts into B6.C-H2(<bm12>)KhEg (a class II
      mismatch combination) to examine the extent of GAD. Pitavastatin was administered
      orally to mice everyday (3 mg/kg/day). To assess the effect in acute rejection,
      mixed lymphocyte reaction was performed and cytokine mRNA expression was examined
      with ribonuclease protection assay. RESULTS: Pitavastatin significantly prolonged
      allograft survival. Lymphocyte proliferation was inhibited by pitavastatin, and
      RPA showed down-regulation of interleukin-6 in pitavastatin-treated cardiac
      allografts. Allografts in the pitavastatin-treated group after 8 weeks showed
      less GAD compared with the control group. In vitro, pitavastatin suppressed the
      smooth muscle cell proliferation in response to activated T cells and inhibited
      extracellular signal-regulated kinase 1/2 activation. CONCLUSION: Pitavastatin
      could be effective in the suppression of acute rejection and GAD development in
      cardiac transplantation.

PMID- 17452901
TI  - Rapamycin enhances the number of alloantigen-induced human CD103+CD8+ regulatory
      T cells in vitro.
AB  - BACKGROUND: Regulatory T cells (T(reg) cells) may be operational in both the
      induction and maintenance of transplantation tolerance. We recently showed that
      alloantigen-induced CD103+ CD8+ T cells strongly suppressed T-cell proliferation
      in mixed lymphocyte culture (MLC) via a contact-dependent mechanism. CD103
      directs T lymphocytes to their ligand E-cadherin, which is expressed on renal
      tubular epithelial cells, and CD103+ CD8+ T cells have been described to be
      present in late renal allograft rejection. METHODS: We studied the influence of
      prednisolone, cyclosporin, tacrolimus, CD25 monoclonal antibodies, rapamycin, and
      mycophenolate mofetil (MMF) on the development and functional activity of
      alloantigen-activated CD103+ CD8+ T cells in MLC. RESULTS: Calcineurin
      inhibitors, MMF, and CD25mAb did not influence the number of CD103 expressing
      CD8+ T cells. In contrast, corticosteroids diminished CD103 expression on
      alloactivated CD8+ T cells, which appeared to be caused by their inhibitory
      action on myeloid dendritic cells. Addition of rapamycin to allocultures led to
      an increased percentage of CD103+ CD8+ alloreactive T cells. Moreover, in the
      presence of rapamycin, these cells tended to show higher suppressive capacity.
      CONCLUSIONS: Alloreactive CD103+ CD8+ T(reg) cells may expand and exert their
      suppressive function during immunosuppressive treatment with rapamycin. These
      data are relevant in the design of immunosuppressive drug regimens intended to
      induce and/or maintain transplantation tolerance.

PMID- 17452902
TI  - Regulatory T-cells in the graft and the risk of acute graft-versus-host disease
      after allogeneic stem cell transplantation.
AB  - BACKGROUND: FOXP3+ regulatory T-cells (Treg) are important regulators of allo
      reactivity and may therefore represent an important predictor for the risk of
      graft versus-host disease (GVHD) after allogeneic stem cell transplantation.
      METHODS: To determine the clinical significance of Treg-content in stem cell
      grafts, we analyzed 58 human leukocyte antigen (HLA)-identical sibling donors (34
      patients received myeloablative and 24 patients reduced intense conditioning
      regimens) and correlated the Treg frequency with clinical outcome after stem cell
      transplantation (SCT). RESULTS: A mean value of 9.1 x 10(6) CD4+ FOXP3+ Treg per
      kg body weight (bw) of the recipient was transplanted (ranging from 0.7 to 33.7 x
      10(6) Treg/kg bw). Graft content of Treg correlated with mononuclear cells and
      CD3+ T-cells. Patients receiving low numbers of Treg (Treg(low)) after
      myeloablative conditioning for SCT had a significantly increased cumulative
      incidence of 76% for acute GVHD when compared with 23% for individuals receiving
      high numbers of Treg (Treg(high)). This observation, however, was not made in
      patients after reduced intense conditioning-SCT. Notably, relapse rate was not
      significantly different between Treg(low) and Treg(high) patients in either
      patient group and overall survival was even increased in Treg(high) patients
      after myeloablative SCT. Finally, low Treg graft levels represent an independent
      prognostic factor in multivariate analysis for the appearance of acute GHVD.
      CONCLUSION: Donor-derived Treg might be of particular significance for the
      development of acute GVHD after myeloablative SCT using HLA-identical sibling
      donors.

PMID- 17452903
TI  - Rapamycin inhibits proliferation of Epstein-Barr virus-positive B-cell lymphomas
      through modulation of cell-cycle protein expression.
AB  - BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious
      complication of solid organ and bone marrow transplantation and is closely
      associated with Epstein-Barr virus (EBV) infection. We have previously shown that
      rapamycin (RAPA) directly inhibits the in vitro and in vivo proliferation of EBV
      infected B lymphoblastoid cell lines (SLCL), derived from patients with PTLD, by
      arresting cells in the G1 phase of the cell cycle. The aim of this study is to
      elucidate the mechanism by which RAPA causes cell cycle arrest in EBV+ B cells.
      METHODS: SLCL were cultured without or with RAPA (10 ng/ml) and G1-associated
      cell cycle proteins were analyzed by immunoblot and densitometric analysis. CDK
      complexes were immunoprecipitated and incubated with retinoblastoma protein (Rb)
      substrate. Kinase activity of the complex was determined by Western blot with
      anti-phospho-Rb antibodies. RESULTS: We show that RAPA decreased both Cyclin D2
      and Cyclin D3 protein levels. Furthermore, RAPA decreased the protein levels of
      cyclin dependent kinase 4 (CDK4) and increased the expression of the CDK
      inhibitor p27. In contrast, expression of the CDK inhibitor p21 was markedly
      inhibited by RAPA in the SLCL. Finally, in vitro kinase assays revealed that
      downstream hyperphosphorylation of Rb by CDK complexes was also decreased by
      RAPA. CONCLUSION: The results presented here elucidate key targets of RAPA
      induced cell cycle arrest, provide insight into the growth pathways of EBV+ B
      cell lymphomas, and demonstrate the potential for RAPA as a therapeutic option in
      the treatment of PTLD and other EBV+ lymphomas.

PMID- 17452904
TI  - Experimental and clinical significance of antinuclear antibodies in liver
      transplantation.
AB  - Histone H1 and high-mobility group box 1 (HMGB1) proteins are known to initiate
      an immune reaction, and the corresponding antibodies (Abs) possess
      immunosuppressive activity. In the present study, we aimed to evaluate the
      immunological role of antinuclear Abs in experimental and clinical liver
      transplantation. In a rat tolerogenic orthotopic liver transplantation (OLT)
      model, antihistone H1 and HMGB1 titers were induced during the rejection and
      tolerance induction phases, respectively. Those Ab responses also were confirmed
      in a drug-induced tolerance model (acute rejection model + cyclosporin A [0 to 14
      days after OLT]). We also found a similar tendency in our clinical drug-free
      patient (who experienced complete cessation of any immunosuppressive treatments)
      and that antinuclear Abs induced in the serum after cessation of
      immunosuppressants play a part of immune privilege in this patient. These results
      suggest that antinuclear Abs are important factors for overcoming rejection and
      the subsequent tolerance induction in liver transplantation.

PMID- 17452905
TI  - Antibodies against glutathione S-transferase T1 (GSTT1) in patients with GSTT1
      null genotype as prognostic marker: long-term follow-up after liver
      transplantation.
AB  - An objective to improve the evolution of transplants is to identify risk
      biomarkers of morbidity and loss of allograft. In liver transplant (LTX)
      recipients, an association has been demonstrated between the presence of mismatch
      for glutathione S-transferase T1 (GSTT1) and the development of de novo immune
      hepatitis (IH). In 419 LTX patients we analyzed, for a period of 1 to 14 years,
      the development of "atypical" autoantibodies directed against GSTT1 and their
      relationship with the mismatch for GSTT1 genotype and with the risk for
      developing de novo IH. A total of 6.9% LTX recipients had "atypical"
      autoantibodies and 24 showed mismatch (recipient/donor) for GSTT1 genotype. From
      this last group, up to 70% developed de novo IH and graft dysfunction after LTX
      (95% confidence interval: 17.4-37.5 months). In LTX recipients with a GSTT1 null
      genotype, the evaluation of "atypical" autoantibodies is useful for monitoring
      the development of de novo IH.

PMID- 17452906
TI  - Blood concentration curve of cyclosporine: impact of itraconazole in lung
      transplant recipients.
AB  - Although the influence of cytochrome P450 inhibitory drugs on the area under the
      curve (AUC) of cyclosporine (CsA) has been described, data concerning the impact
      of these substances on the shape of the blood concentration curve are scarce. By
      assessment of CsA blood levels before and 1, 2, and 4 hr after oral intake (C0,
      C1, C2, and C4, respectively) CsA profiling examinations were performed in 20
      lung transplant recipients taking 400 mg, 200 mg, and no itraconazole,
      respectively. The three groups showed comparable results for C0, C2, and AUC(0
      12). Greater values were found for Cmax, Cmax-C0, peak-trough fluctuation and
      rise to Cmax in favor of the non-itraconazole group. Additionally, tmax was
      shorter in the non-itraconazole group. Comedication with the metabolic inhibitor
      itraconazole is associated with a flattening of the CsA blood concentration
      profile in lung transplant recipients. These changes cannot be assessed by
      isolated C0, C2, or AUC(0-12) values alone.

PMID- 17452907
TI  - Cold heparinized lactated Ringers with procaine (HeLP) preservation fluid in 266
      living donor kidney transplantations.
AB  - Since the 1960s simple inexpensive cold lactated Ringers with additives has been
      used for short-term cold preservation of kidneys from living donors. We performed
      266 living donor kidney transplantations from January 22, 2003 to October 30,
      2006. Donor allografts were recovered laparoscopically and flushed with cold
      heparin, lactated Ringer's and procaine (HeLP) solution. Warm and cold ischemic
      times were typically <45 min and <90 min, respectively. The mean follow up was
      21.6+/-12.2 months. There was no delayed graft function. Actuarial 1-year patient
      and graft survival were 98.6% and 98.1%, respectively. The creatinine at 1 year
      was 1.46+/-0.51 mg/dL. The cumulative incidences of acute cellular rejection at
      6, 12, 18, and 24 months were 3.0%, 7.1%, 10.2%, and 11.7%. There were no
      identifiable side effects attributed to the HeLP solution. This study documents
      the effectiveness of cold HeLP as a flushing and short-term preservation fluid
      for living donor kidney transplantation with excellent results and significant
      cost benefit because of its low cost.

PMID- 17452908
TI  - Interventional trials involving patients cannot be performed safely without a
      control group treated with the standard of care.

PMID- 17452911
TI  - Race and living kidney donors.

PMID- 17452912
TI  - A report of the Lisbon Conference on the care of the kidney transplant recipient.

PMID- 17452913
TI  - A novel double-row rotator cuff repair exceeds strengths of conventional repairs.
AB  - Double-row rotator cuff repairs are becoming popular because of their ability to
      improve initial ultimate failure load for full-thickness rotator cuff tears,
      especially in middle-aged to elderly patients. We hypothesized a quasi-double-row
      repair using a combination of transosseous sutures, anchors, and double knots
      (TOAK technique) would exceed the clinically relevant 250-N load threshold and
      the initial mean ultimate failure loads of anchor-only and transosseous suture
      only fixation. In simulated full-thickness supraspinatus tears in cadavers (mean
      age, 62 years; range, 50-77 years), failure loads of two repair techniques were
      compared with a TOAK repair using sutures and bioabsorbable anchors. Radiographic
      densitometry was conducted on all humeral heads. Testing was performed at 6 mm
      per minute in 18 bones in the following three groups (n = 6 per group): (1)
      transosseous suture-only with weave-type stitch and single-knot fixation; (2)
      anchor-only with horizontal mattress stitch and single-knot fixation; and (3)
      TOAK. The mean ultimate failure load was 238 N for the transosseous suture-only
      group and 215 N for the anchor-only group. Although the bones had lower density,
      TOAK specimens failed at 55% to 67% higher loads (mean, 404 N) than the other
      groups. These data support further evaluation of the TOAK technique for full
      thickness supraspinatus tears in middle-aged to elderly patients.

PMID- 17452914
TI  - Perioperative antibiotics should not be withheld in proven cases of
      periprosthetic infection.
AB  - Intraoperative tissue or fluid culture remains the gold standard in diagnosing
      periprosthetic infection. However, an organism is not always isolated from
      intraoperative cultures. We asked whether preoperative antibiotics interfered
      with the isolation of organisms from intraoperative tissue samples. We
      hypothesized organisms isolated from preoperative joint aspirate correspond to
      those cultures from intraoperative specimens. We retrospectively reviewed 171
      patients undergoing TKA, diagnosed with periprosthetic infections from 2000 to
      2005, who had a positive preoperative aspiration culture. The details of any
      antibiotics given to the patients preoperatively were documented. Seventy-two of
      171 patients received preoperative antibiotics before surgery. Intraoperative
      culture was negative in nine of the 72 patients who received antibiotics: a false
      negative rate of 12.5%. An organism could not be isolated from intraoperative
      samples in eight of the 99 patients who did not receive preoperative antibiotics:
      a false-negative rate of 8%. We observed no difference in the incidence of false
      negative cultures between the two groups. The organisms isolated from the
      aspirate culture were identical to their intraoperative counterparts in 97% of
      the cases. Administration of preoperative antibiotics to patients with a positive
      preoperative joint aspirate did not interfere with the isolation of the infecting
      organism from intraoperative culture samples more than when antibiotics were
      withheld.

PMID- 17452915
TI  - Sterilization wrap inspections do not adequately evaluate instrument sterility.
AB  - Orthopaedic procedures rely on strict sterilization techniques to prevent
      surgical site infections. Surgical instrument trays are wrapped for
      sterilization, and these wraps routinely are inspected by operating room
      personnel to evaluate for breaches before using the contained instruments. The
      sensitivity of this practice for detecting wrap defects has not been established.
      We divided 90 sterilization wraps into groups with no defect and with six sizes
      of defects ranging from 1.1 to 10.0 mm in diameter. Puncture-type defects were
      created using nails of known diameter. All wraps were evaluated by medical
      personnel for evidence of a breach. Detection rates ranged from 6.7% to 96.7%
      from the smallest to largest defects, respectively. The potential for bacterial
      transmission through wrap defects also was evaluated, and contaminated nails of
      the smallest size transmitted bacterial contaminants through the wrap during the
      creation of puncture defects. Thus, substantial perforations in sterilization
      wraps frequently are missed when evaluated with commonly used techniques. Defects
      with a diameter approximately that of a pencil (6.7 mm) were missed 18% of the
      time, although contamination can be transmitted by a nail with the diameter of a
      pin (1.1 mm). These results raise questions about a common screening method.

PMID- 17452916
TI  - Anterior lumbar fusion in Pott's disease.
AB  - Although most lumbar lesions associated with spinal tuberculosis can be
      satisfactorily resolved with nonoperative treatment, there are cases in which
      surgery is indicated. Between July 1982 and December 2003 we retrospectively
      reviewed 51 patients who were operated by anterior debridement and fusion. Twelve
      patients were lost to followup and one died due to inferior vena cava tear.
      Followup of 38 patients ranged from 2 to 10 years (average 4 years). There were
      22 male and 16 female patients, average age 35 years (range, 8-65 years); upper
      lumbar area (L1-L3) was involved in 17 cases, lower lumbar (L3-L5) in 19 and
      lumbosacral area in two patients; 28 patients had two-body and 10 had three-body
      involvement. In 35 patients we performed single stage debridement and fusion.
      More recently three patients had two stage (instrumentation plus debridement and
      fusion) procedure. Followup was based on subjective relief, recovery of neural
      deficit and consolidation at fusion site. Thirty-six out of 38 patients had
      complete relief from pain and discomfort along with radiographic fusion. Five
      patients who had neural deficit recovered completely. Surgical treatment of
      lumbar spinal tuberculosis in selected cases gives satisfactory results.

PMID- 17452917
TI  - Treatment of intraspinal tuberculoma.
AB  - Neurological manifestations in spinal tuberculosis often occur secondary to
      vertebral involvement. However, tuberculoma of the spinal cord or extradural
      granuloma without radiological evidence of vertebral involvement may be
      responsible for neurological complications. We report 22 patients with
      intraspinal tuberculoma (19 extradural, three intramedullary) ranging in age from
      17 to 70 years. Three patients had a history of paraplegia of acute onset (within
      12 hours of the appearance of neural deficit). Only four patients had spinal
      tenderness, and bone involvement could be seen on plain radiographs in only three
      patients. Extradural tubercular granuloma without vertebral involvement is
      uncommon. Of the 15 extradural tuberculoma patients who had a CT scan and/or MRI,
      only five had no osseous involvement. Laminectomy and surgical decompression was
      performed in all 19 patients with extradural granuloma. Thirteen patients showed
      complete neural recovery within 2 years. Of the three patients with
      intramedullary involvement, one underwent myelotomy and decompression and died
      within 2 months of surgery. The other two patients were treated nonoperatively
      with antitubercular therapy and showed complete neural recovery. All patients
      received antitubercular therapy for a minimum of 1 year. Intraspinal tubercular
      granuloma should be considered in the differential diagnosis when a case of
      spinal tumor syndrome is encountered in an endemic zone of tuberculosis.

PMID- 17452918
TI  - Anterior instrumentation in tuberculous spondylitis: is it effective and safe?
AB  - Radical anterior debridement and strut grafting is the gold standard in the
      surgical treatment of tuberculosis spondylitis. For many years anterior
      instrumentation was avoided due to concerns about infection until recently. We
      investigated the effectiveness and safety of anterior instrumentation for
      different sites of involvement, number of involved levels, and different age
      groups in 100 consecutive patients (mean age, 44.3 +/- 12.4). We measured
      preoperative, postoperative, and final kyphotic deformities radiographically and
      looked for the presence of fusion. Patients had a minimum followup of 3 years
      (average, 4.5 years; range, 3-6 years). Addition of anterior instrumentation was
      effective in the correction of kyphotic deformity (19.8 degrees +/- 7.3 degrees)
      and facilitated solid fusion, with an average loss of 1.6 degrees +/- 1.8
      degrees. Of the 44 patients with neurologic symptoms, 40 (90.9%) achieved full
      and four (9.1%) achieved partial recovery. There were no apparent pseudarthroses
      and implant failures. All patients demonstrated clinical healing of tuberculosis
      without recurrence and reactivation. All domains of the SRS-22 questionnaire
      showed improvements at the last followup. Anterior instrumentation represents a
      safe and effective method for the treatment of tuberculosis spondylitis, and it
      may be the ideal stabilization method thanks to less segment fusion, single
      approach, and obviating the need for external immobilization.

PMID- 17452919
TI  - Curettage of biopsy-diagnosed grade 1 periacetabular chondrosarcoma.
AB  - Intralesional excision of intraosseous grade 1 periacetabular chondrosarcoma may
      seem an attractive alternative to the current recommendation of joint
      sacrificing, en bloc resection. We report eight patients who initially underwent
      this treatment to identify if local tumor control can be achieved consistently.
      All patients had a percutaneous biopsy that was interpreted as grade 1
      chondrosarcoma. The final histology after curettage indicated Grade 1
      chondrosarcoma in five patients, Grade 2 in two, and dedifferentiated
      chondrosarcoma in one. Three of the five patients with true grade 1
      chondrosarcoma have been free of disease at a median followup of 108 months. The
      other two patients with grade 1 chondrosarcoma on the curettage specimen recurred
      as higher-grade tumors. Three patients died of high-grade chondrosarcoma at a
      median of 23 months (range 17-72 months). Overall, the majority of patients in
      this cohort had either a misdiagnosis or recurrence of higher-grade disease.
      Based on these observations, in the absence of a predictable method to identify
      the true intraosseous grade 1 chondrosarcomas of the pelvis, curettage must be
      undertaken with the understanding that a percutaneous biopsy may misrepresent the
      histologic grade and that curettage may result in a higher risk of recurrence.

PMID- 17452920
TI  - Disease- and recurrence-free survival after surgical resection of solitary bone
      metastases of the pelvis.
AB  - For patients with advanced cancer who present with or develop a bone lesion as
      the only focus of cancer beyond the primary site, en bloc resection of the
      metastasis may optimize local tumor control, provide durable pain relief, and
      possibly prolong patient survival. For patients with pelvic metastasis, however,
      this surgery can be associated with a high risk of complications. We analyzed
      fourteen consecutive patients with a solitary metastasis to the bony pelvis who
      underwent en bloc resection to determine if the benefits of surgery outweigh the
      surgical morbidity. The epicenter of the tumor was isolated to the ilium (four
      patients), the pubis (one patient), and the ischium (three patients), or to the
      periacetabular region (six patients). Surgical margins were negative for tumor in
      13 of 14 patients. No local recurrence developed at last follow-up for six
      survivors (median 74.5 months) and eight non-survivors (median 53 months). Local
      pain relief was achieved in all patients. For patients with a solitary pelvic
      metastasis, the favorable median patient survival justifies consideration of a
      radical surgical approach to achieve pain palliation and tumor control.

PMID- 17452921
TI  - Reconstruction with modular hemipelvic prostheses for periacetabular tumor.
AB  - Periacetabular resections for primary bone sarcoma and metastatic disease require
      reconstruction to restore weight-bearing along anatomic axes. We designed a
      modular hemipelvic prosthetic system to reconstruct the pelvis and evaluated the
      early clinical outcome of the prosthesis using 3-year survival rate, local
      recurrence rate, Musculoskeletal Tumor Society (MSTS) 93 function score, and
      complications. We retrospectively reviewed 28 patients who had pelvic tumor
      resections and reconstructions using the new hemipelvic prostheses between 2001
      and 2005. Sixteen (57.1%) patients had Types II and III (periacetabular and
      pubis) pelvic resections, seven had Types I and II (periacetabular and ilium)
      pelvic resections, and five had Type II (periacetabular) pelvic resection. Six
      patients with osteosarcoma had chemotherapy. None received radiation therapy.
      Patient survival status, function, and complications were evaluated at a mean
      followup of 30 months (range, 10-59 months). Fifteen patients were free of
      disease, eight patients died of disease, and five patients were alive with
      disease. The overall survival rate was 67.1% at 3 years. Twenty-five percent had
      local recurrence and 21% had metastasis. The mean MSTS 93 score was 60. Deep
      infection occurred in four patients; dislocation occurred in one patient. The
      results are encouraging because of the acceptable complication rate and
      satisfactory functional outcome.

PMID- 17452922
TI  - Soft tissue sarcoma resection volume associated with wound-healing complications.
AB  - Limb-salvage surgery has become the standard of care for most soft tissue
      sarcomas. While primary closure is often possible, it is frequently complicated
      by wound-healing complications in the setting of previously irradiated tissue and
      surgical wounds closed under tension. We sought to identify a relationship
      between the volume of resected soft tissue and the rate of wound-healing
      complications. We retrospectively reviewed 108 patients who were treated over a
      17-month period for soft-tissue sarcomas using limb-salvage methods. Of these, 87
      patients were treated with primary wound closure and 21 patients underwent
      primary muscle flap closure at the time of wide surgical excision. Of the 87
      patients treated with primary wound closure, the mean volume of resected tissue
      in the group with wound-healing complications was greater than that the group
      that healed without complications. The mean volume of resected tissue in the
      group with wound-healing complications was 919 cm3 +/- 1173 cm3 and the mean
      volume of resected tissue in the group without wound-healing complications was
      456 cm3 +/- 704 cm3. Mean volume of resected tissue in the group of patients
      treated with primary flap coverage was 1908 cm3, over twice as large as the mean
      volume of resected tissue in the group of patients treated with primary closure.

PMID- 17452923
TI  - Kyphus correction in spinal tuberculosis.
AB  - Late-onset paraplegia is best avoided by correcting severe kyphosis in the
      active, healing, or healed stages of spinal tuberculosis. We report 16 patients
      with dorsal or dorsolumbar spinal TB--nine with paraplegia, seven without
      paraplegia--who underwent kyphus correction. Nine patients had active, five
      partially treated, and two healed disease. The patients ranged in age from 3 to
      38 years and had a mean kyphosis of 58.5 degrees (range, 35 degrees-76 degrees).
      Mean vertebral body involvement on computed tomography was 4.2 (2-9), and mean
      initial vertebral body loss was 1.76 (1-2.6). The sequential steps for kyphus
      correction were anterior corpectomy, shortening of the posterior column,
      posterior instrumentation and anterior gap grafting, and posterior fusion as a
      single-stage procedure by the extrapleural anterolateral (costotransversectomy)
      approach. Minimum followup was 3 months (range, 3-36 months). All but one patient
      with neural deficit showed complete neural recovery. Mean kyphosis correction was
      27.3 degrees (range, 9 degrees-42 degrees). Mean correction loss on 1-year
      followup was 1.4 degrees (range, 0 degrees-4 degrees).

PMID- 17452924
TI  - Fluid support worsens outcome and negates the benefit of protective antigen
      directed monoclonal antibody in a lethal toxin-infused rat Bacillus anthracis
      shock model.
AB  - OBJECTIVE: The aim of this study was to test the effects of normal saline
      treatment either alone or in combination with protective antigen-directed
      monoclonal antibody in a lethal toxin-infused rat model of anthrax sepsis.
      DESIGN: Prospective controlled animal study. SETTING: Animal research laboratory.
      SUBJECTS: Sprague-Dawley rats (n = 539). INTERVENTIONS: We initially tested the
      efficacy of three normal saline doses (5, 10, or 20 mL/kg/hr intravenously for 24
      hrs) or none (controls) started when rats were treated with either lethal toxin
      (24-hr infusion) or, for comparison, lipopolysaccharide (24-hr infusion) or
      Escherichia coli (intravenous bolus). We then investigated delaying normal saline
      for 6 hrs or combining it with protective antigen-directed monoclonal antibody
      following lethal toxin challenge. MEASUREMENTS AND MAIN RESULTS: Dose did not
      alter the effects of normal saline with any challenge (p not significant for all)
      or when combined with protective antigen-directed monoclonal antibody, so this
      variable was averaged in analysis. In initial studies, normal saline decreased
      mortality (mean hazards ratio of survival +/- SE) significantly with E. coli
      challenge (-0.66 +/- 0.25, p = .009 averaged over normal saline dose) but not
      lipopolysaccharide (-0.17 +/- 0.20). In contrast, normal saline increased
      mortality significantly with lethal toxin (0.69 +/- 0.20, p = .001) in a pattern
      different from E. coli and lipopolysaccharide (p <or= .002 for each). In
      subsequent studies, normal saline alone once again increased mortality (0.8 +/-
      0.3, p = .006), protective antigen-directed monoclonal antibody alone reduced it
      (-1.7 +/- 0.8, p = .03), and the combination had intermediate effects that were
      not significant (0.04 +/- 0.3). CONCLUSIONS: These findings raise the possibility
      that normal saline treatment may actually worsen outcome with anthrax lethal
      toxin. Furthermore, lethal toxin-directed therapies may not be as beneficial when
      used in combination with this type of fluid support.

PMID- 17452925
TI  - Static and dynamic components of esophageal and central venous pressure during
      intra-abdominal hypertension.
AB  - OBJECTIVE: To investigate the effects of intra-abdominal hypertension on
      esophageal and central venous pressure considering values obtained at end
      expiration (i.e., in static conditions) and during tidal volume delivery (i.e.,
      in dynamic conditions). DESIGN: Retrospective (pigs) and prospective, randomized,
      controlled (rats) trial. SETTING: Animal laboratory of a university hospital.
      SUBJECTS: Six female pigs and 15 Sprague Dawley male rats. INTERVENTIONS: During
      anesthesia and paralysis, animals' abdomens were inflated with helium.
      MEASUREMENTS AND MAIN RESULTS: Abdominal pressure was measured by intraperitoneal
      catheter. In pigs, esophageal pressure and central venous pressure were
      continuously measured while inflating the abdomen together with hemodynamic
      assessment. In rats, the abdomen was inflated after the random application of
      three levels of positive end-expiratory pressure. Data are shown as mean +/- SD.
      At end-expiration, esophageal pressures were similar before and after abdominal
      inflation (p = .177). In contrast, the dynamic component significantly rose after
      intra-abdominal hypertension, from 3.2 +/- 0.7 cm H2O to 10.0 +/- 2.3 cm H2O (p <
      .001), and was correlated with peritoneal pressure (linear regression, R2 = .708,
      p < .001). Positive end-expiratory pressure significantly influenced static
      esophageal pressure during intra-abdominal hypertension (p = .002) but not
      dynamic pressures. Static central venous pressure rose with intra-abdominal
      hypertension from 4.1 +/- 1.5 cm H2O to 6.7 +/- 1.8 cm H2O (p = .043), more so
      the dynamic component (from 2.9 +/- 0.8 cm H2O to 9.3 +/- 3.1 cm H2O, p = .02).
      Dynamic changes of esophageal pressures correlated with dynamic changes of
      central venous pressure (linear regression, R2 = .679, p < .001). Mean values of
      central venous pressure significantly increased with intra-abdominal hypertension
      from 7.7 +/- 1.5 cm H2O to 12.7 +/- 2.6 cm H2O (p = .006), whereas transmural
      central venous pressure and intrathoracic blood volume did not change
      significantly. CONCLUSIONS: Dynamic changes of esophageal pressure occurred
      during intra-abdominal hypertension, whereas end-expiratory pressure was affected
      by high positive end-expiratory pressure levels. Provided that central venous
      pressure changes reflect esophageal pressure, central venous pressure itself
      cannot be relied on to guide resuscitation in patients with intra-abdominal
      hypertension, particularly when abdominal pressures are changing over short
      periods of time.

PMID- 17452926
TI  - The association of nicotine replacement therapy with mortality in a medical
      intensive care unit.
AB  - OBJECTIVE: Smokers admitted to the intensive care unit may receive nicotine
      replacement therapy to prevent withdrawal. However, the safety of nicotine
      replacement in the critically ill has not been studied. The objective of this
      study was to determine the impact of nicotine replacement on the outcome of
      critically ill patients. DESIGN: Retrospective, case-control. SETTING: The
      medical intensive care unit of a tertiary academic hospital. PATIENTS: Patients
      who were active smokers at admission to the intensive care unit were included in
      the study. Those who received nicotine replacement therapy were considered as
      cases, and those who did not receive nicotine replacement were considered as
      controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For each of the 90
      cases, one control smoker who did not receive nicotine replacement therapy was
      selected based on the severity of illness and then age. Outcome was measured by
      hospital mortality and 28-day intensive care unit-free days, defined as the
      number of days spent outside of intensive care or without mechanical ventilation
      by a living patient following admission to intensive care. The mean mortality
      rate predicted by the Acute Physiology and Chronic Health Evaluation III was 9.2%
      for the cases compared with 10.3% for the controls (p = .7127). The observed
      hospital mortality rate was 20% in the cases vs. 7% in the control group (p =
      .0085). When adjusted for the severity of illness and invasive mechanical
      ventilation, nicotine replacement therapy was independently associated with
      increased mortality (odds ratio, 24.6; 95% confidence interval, 3.6-167.6; p =
      .0011). The mean (sd) 28-day intensive care unit-free days were 20.7 (10.5) in
      the case group compared with 23.4 (7.1) in the control group (p = .0488).
      CONCLUSIONS: Our study shows that nicotine replacement therapy is associated with
      increased hospital mortality in critically ill patients. However, because of the
      limitations of the study, a future study based on a better case-control design is
      warranted.

PMID- 17452927
TI  - Pronounced elevation of resistin correlates with severity of disease in severe
      sepsis and septic shock.
AB  - OBJECTIVE: Resistin induces insulin resistance in mice. In humans, recent data
      suggest that resistin functions as a proinflammatory cytokine. Here, we studied
      resistin up to 2 wks after admission in patients with septic shock and/or severe
      sepsis. DESIGN: Two prospective studies of patients with sepsis and in vitro
      studies of resistin interaction with monocytes. SETTING: Intensive care unit at
      Karolinska University Hospital and Center for Infectious Medicine, Karolinska
      Institute, Huddinge, Sweden. PATIENTS: Twenty-nine patients with severe sepsis
      and 66 with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Ninety-five patients were studied, 25 of whom died within 28 days. Resistin and
      cytokine levels and routine biochemistry were measured at three to six defined
      time points during the first 2 wks after admission and were correlated to other
      cytokines, glucose levels, body mass index, Acute Physiology and Chronic Health
      Evaluation II, and Sepsis-related Organ Failure Assessment scores. Serum resistin
      was significantly elevated compared with healthy controls (p < .000001) and
      correlated with severity of disease as measured by Acute Physiology and Chronic
      Health Evaluation II and Sepsis-related Organ Failure Assessment scores, with an
      increasingly strong degree of correlation over time. Median levels were four- to
      eight-fold higher than controls and remained high up to 2 wks after admission to
      the intensive care unit. Levels correlated with interleukin-6, interleukin-8,
      interleukin-10, tumor necrosis factor-alpha, creatinine, D-dimer, and lactate,
      but not with p-glucose or body mass index. In vitro, resistin was released from
      monocytes after stimulation with either lipopolysaccharide or high mobility group
      box 1 protein. Recombinant resistin itself up-regulated intercellular adhesion
      molecule-1 on monocytes. CONCLUSIONS: This is the first study assessing systemic
      levels of resistin in patients with septic shock/severe sepsis. We show that
      resistin is a marker of severity of disease and possibly a mediator of the
      prolonged inflammatory state seen in infected critically ill patients. Further
      exploration of resistin as a therapeutic target and marker of disease is merited.

PMID- 17452928
TI  - Gender differences in the innate immune response and vascular reactivity
      following the administration of endotoxin to human volunteers.
AB  - OBJECTIVE: To determine gender differences in the innate immune response and
      vascular reactivity during human endotoxemia. DESIGN: Clinical experimental
      study. SETTING: University medical center intensive care research unit. SUBJECTS:
      Fifteen female and 15 male volunteers. INTERVENTIONS: Intravenous injection of 2
      ng/kg Escherichia coli lipopolysaccharide. MEASUREMENTS AND MAIN RESULTS: C
      reactive protein, leukocytes, and cytokines were measured at regular time
      intervals as indicators of inflammation. Heart rate and blood pressure were
      continuously monitored. Forearm blood flow and the responsiveness of forearm
      vessels to the intrabrachial infusion of norepinephrine (1-3-10-30 ng/min/dL)
      were measured before and 4 hrs after the administration of endotoxin using venous
      occlusion plethysmography. Differences were tested with repeated-measures
      analysis of variance. Females showed a more proinflammatory response to
      lipopolysaccharide than males, illustrated by a higher rise in C-reactive protein
      (42 +/- 3 vs. 29 +/- 3 mg/L, p = .002) and more leukocyte sequestration
      (leukopenia 1.8 +/- 0.1 x 10 vs. 2.4 +/- 0.1 x 10, p = .003). The increase in
      cytokine levels showed a more proinflammatory pattern in females as reflected by
      a higher increase in tumor necrosis factor-alpha (965 +/- 193 vs. 411 +/- 35
      pg/mL, p < .0001), whereas the increase of the anti-inflammatory interleukin-10
      was not significantly different (95 +/- 15 pg/mL in females vs. 129 +/- 15 pg/mL
      in males, p = .288). Females exhibited higher baseline levels (9.9 +/- 1.1 vs.
      7.0 +/- 0.8 pg/mL in males, p = .042) and an augmented increase in
      lipopolysaccharide-binding protein, which may explain the more pronounced
      inflammatory response in females. The lipopolysaccharide-induced change in heart
      rate was not significantly different between the genders, whereas blood pressure
      decreased more in females (p < .0001). Lipopolysaccharide administration
      significantly attenuated the norepinephrine sensitivity in males (p = .002),
      whereas no lipopolysaccharide-induced effect was observed in females (p = .552;
      difference between groups, p = .045). CONCLUSIONS: During experimental human
      endotoxemia, females showed a more pronounced proinflammatory innate immune
      response associated with less attenuation of norepinephrine sensitivity. These
      findings may be relevant in view of the profound and incompletely explained
      differences in incidence and outcome of sepsis among male and female patients.

PMID- 17452929
TI  - Evaluation of tris-hydroxymethylaminomethane on reversing coagulation
      abnormalities caused by acidosis in pigs.
AB  - OBJECTIVE: To investigate the effect of tris-hydroxymethylaminomethane (THAM) pH
      neutralization on reversing coagulation abnormalities caused by acidosis. DESIGN:
      Random and controlled study. SETTING: Animal research facility and laboratory.
      SUBJECTS: Yorkshire swine (n = 18). INTERVENTIONS: Acidosis was induced in 12
      pigs by infusing 0.2 M hydrochloric acid (HCl). When the target pH of 7.1 was
      achieved, the pigs were infused with either 0.3 M THAM to achieve pH of 7.4
      (intervention group) or an equal volume of lactated Ringer's solution (acid
      control group). MEASUREMENTS AND MAIN RESULTS: Blood samples were taken at
      baseline, 15 mins after reaching pH of 7.1, and 15 mins after THAM pH
      neutralization. Coagulation function was assessed by thrombin generation,
      prothrombin time, activated partial thromboplastin time, activated clotting time,
      and thromboelastography (maximum clot formation time [R+K], clotting rapidity
      [alpha], and clot strength [maximum amplitude]). An additional six pigs (sham
      group) were infused with THAM, and an equal volume of fluid as the 12
      coagulopathic pigs was given to assess effects of THAM and hemodilution.
      Comparisons were made using a mixed model analysis of variance. No change in any
      indexes of coagulation was observed in sham pigs. Compared with baseline,
      acidosis of pH 7.1 decreased base excess from 6.6 +/- 0.5 mM to -12.4 +/- 0.5 mM;
      reduced fibrinogen levels to 72% +/- 2%, platelet counts to 53% +/- 3%, thrombin
      generation to 58% +/- 4%, alpha to 84% +/- 2%, and maximum amplitude to 75% +/-
      3%; and prolonged prothrombin time to 113% +/- 2%, partial thromboplastin time to
      122% +/- 4%, activated clotting time to 124% +/- 3%, and R + K to 119% +/- 3%
      (all p < .05). THAM infusion corrected pH to 7.40 +/- 0.02 and base excess to 2.6
      +/- 0.9 mM (p < .05). However, there were no differences in thrombin generation,
      prothrombin time, partial thromboplastin time, activated clotting time, R+K,
      alpha, or maximum amplitude between the groups with or without pH correction.
      CONCLUSIONS: Acidosis impaired coagulation by depleting clotting factors,
      inhibiting thrombin generation, and affecting clot strength and stability. THAM
      corrected acid-base deficit but did not acutely reverse the coagulation
      abnormalities in the model.

PMID- 17452930
TI  - Proactive palliative care in the medical intensive care unit: effects on length
      of stay for selected high-risk patients.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of proactive
      palliative care consultation on length of stay for high-risk patients in the
      medical intensive care unit (MICU). DESIGN: A prospective pre/post nonequivalent
      control group design was used for this performance improvement study. SETTING:
      Seventeen-bed adult MICU. PATIENTS: Of admissions to the MICU, 191 patients were
      identified as having a serious illness and at high risk of dying: 65 patients in
      the usual care phase and 126 patients in the proactive palliative care phase. To
      be included in the sample, a patient had to meet one of the following criteria:
      a) intensive care admission following a current hospital stay of >or=10 days; b)
      age >80 yrs in the presence of two or more life-threatening comorbidities (e.g.,
      end-stage renal disease, severe congestive heart failure); c) diagnosis of an
      active stage IV malignancy; d) status post cardiac arrest; or e) diagnosis of an
      intracerebral hemorrhage requiring mechanical ventilation. INTERVENTIONS:
      Palliative care consultations. MEASUREMENTS AND MAIN RESULTS: Primary measures
      were patient lengths of stay a) for the entire hospitalization; b) in the MICU;
      and c) from MICU admission to hospital discharge. Secondary measures included
      mortality rates and discharge disposition. There were no significant differences
      between the usual care and proactive palliative care intervention groups in
      respect to age, gender, race, screening criteria, discharge disposition, or
      mortality. Patients in the proactive palliative care group had significantly
      shorter lengths of stay in the MICU (8.96 vs. 16.28 days, p = .0001). There were
      no differences between the two groups on total length of stay in the hospital or
      length of stay from MICU admission to hospital discharge. CONCLUSIONS: Proactive
      palliative care consultation was associated with a significantly shorter MICU
      length of stay in this high-risk group without any significant differences in
      mortality rates or discharge disposition.

PMID- 17452931
TI  - Norepinephrine increases tolerance to acute anemia.
AB  - OBJECTIVE: Extreme anemia threatens myocardial oxygen supply by 1) a decline of
      arterial oxygen content and 2) by a decline of mean aortic pressure (MAP) and
      thus coronary perfusion pressure. Standard treatment of low arterial oxygen
      content includes ventilation with pure oxygen and the transfusion of red blood
      cells. However, it is unknown whether the stabilization of MAP and coronary
      perfusion pressure with norepinephrine as the sole therapeutic modality may also
      increase tolerance to extreme anemia and thus improve outcome. DESIGN:
      Prospective, randomized, controlled study. SETTING: Experimental animal
      laboratory of a university hospital. SUBJECTS: A total of 28 anesthetized,
      mechanically ventilated pigs. INTERVENTIONS AND MEASUREMENTS: In the first
      protocol, 14 anesthetized pigs were hemodiluted by exchange of whole blood for 6%
      hydroxyethyl starch (200,000:0.5) until the individual critical hemoglobin
      concentration was reached. For the next 6 hrs, animals were either observed
      without any further intervention (control group) or their MAP was maintained by
      adapted infusion of norepinephrine (norepinephrine group). The main outcome
      variable of this protocol was the 6-hr mortality in both groups. In the second
      protocol, 14 anesthetized pigs received hemodilution until death. In seven
      animals, no intervention was performed during the hemodilution procedure, whereas
      in the other seven animals, MAP was maintained at >60 mm Hg by adapted infusion
      of norepinephrine. The main outcome variable of this protocol was the maximum
      exchangeable blood volume until death. MAIN RESULTS: MAP stabilization with
      norepinephrine reduced the 6-hr mortality at the critical hemoglobin
      concentration from 100% to 14%. Maintaining MAP by adapted norepinephrine
      infusion during the hemodilution procedure allowed for the exchange of 125
      (110/126) (median [quartile 1/quartile 3]) mL/kg blood (163% of blood volume) in
      the norepinephrine group, whereas only 76 (73/91) mL/kg blood (104% of blood
      volume) could be exchanged in the control group. CONCLUSIONS: Application of
      norepinephrine can be judged a first-line intervention to bridge acute anemia via
      a stabilization of MAP and coronary perfusion pressure. However, due to the
      relevant side effects of norepinephrine, its sole long-term use during extreme
      anemia without concomitant transfusion of erythrocytes is not advised.

PMID- 17452932
TI  - Combination antibiotic therapy improves survival in patients with community
      acquired pneumonia and shock.
AB  - OBJECTIVE: To assess whether combination antibiotic therapy improves outcome of
      severe community-acquired pneumonia in the subset of patients with shock. DESIGN:
      Secondary analysis of a prospective observational, cohort study. SETTING: Thirty
      three intensive care units (ICUs) in Spain. PATIENTS: Patients were 529 adults
      with community-acquired pneumonia requiring ICU admission. INTERVENTIONS: None.
      MEASUREMENT AND MAIN RESULTS: Two hundred and seventy (51%) patients required
      vasoactive drugs and were categorized as having shock. The effects of combination
      antibiotic therapy and monotherapy on survival were compared using univariate
      analysis and a Cox regression model. The adjusted 28-day in-ICU mortality was
      similar (p = .99) for combination antibiotic therapy and monotherapy in the
      absence of shock. However, in patients with shock, combination antibiotic therapy
      was associated with significantly higher adjusted 28-day in-ICU survival (hazard
      ratio, 1.69; 95% confidence interval, 1.09-2.60; p = .01) in a Cox hazard
      regression model. Even when monotherapy was appropriate, it achieved a lower 28
      day in-ICU survival than an adequate antibiotic combination (hazard ratio, 1.64;
      95% confidence interval, 1.01-2.64). CONCLUSIONS: Combination antibiotic therapy
      does not seem to increase ICU survival in all patients with severe community
      acquired pneumonia. However, in the subset of patients with shock, combination
      antibiotic therapy improves survival rates.

PMID- 17452933
TI  - Continuous cardiac output monitoring via arterial pressure waveform analysis
      following severe hemorrhagic shock in dogs.
AB  - OBJECTIVES: To determine agreement and correlation between cardiac output
      determined by arterial pressure waveform analysis (PulseCO) and the lithium
      dilution indicator technique (LiDCO) during severe hemorrhagic shock and after
      fluid resuscitation in dogs. DESIGN: Prospective experimental study. SETTING:
      University research laboratory. SUBJECTS: Twelve adult mongrel dogs.
      INTERVENTIONS: Dogs were anesthetized, and selected arteries and veins were
      catheterized. Baseline cardiac output was determined by LiDCO and used to
      calibrate the PulseCO. Hemorrhagic shock was induced by withdrawing blood to
      achieve and maintain a mean arterial pressure of 30-40 mm Hg for 60 mins, and
      cardiac output was measured again using both methods. All dogs were resuscitated
      by administering lactated Ringer's solution intravenously to achieve and maintain
      a mean arterial pressure between 60 and 70 mm Hg. PulseCO and LiDCO values were
      measured at 10 and 120 mins after resuscitation. MEASUREMENTS AND MAIN RESULTS:
      Mean baseline cardiac output was 2.93 +/- 0.45 L/min. PulseCO values
      overestimated cardiac output compared with LiDCO during hemorrhagic shock (2.25
      vs. 0.78 L/min). There were no differences in cardiac output determined by
      PulseCO and LiDCO at 10 and 120 mins after fluid resuscitation. Bland-Altman
      analysis suggested that PulseCO values were inaccurate after hemorrhage,
      producing significant bias with wide limits of agreement and percentage error
      (1.47 +/- 1.46 L/min; 97%). Bias was small but the limits of agreement and
      percentage error were large for cardiac output at 10 and 120 mins after
      resuscitation (-0.1 +/- 1.88 [98%] and -0.17 +/- 1.32 [71%] L/min, respectively).
      There appeared to be a negative but not significant correlation after hemorrhage
      (r = -.45; p = .15). CONCLUSIONS: PulseCO determination of cardiac output does
      not accurately predict rapid decreases in cardiac output or the effects of fluid
      resuscitation in dogs. Recalibration of PulseCO may be necessary after any
      apparent or suspected decrease in cardiac preload, afterload, or contractility.

PMID- 17452935
TI  - ADDRESS (ADministration of DRotrecogin alfa [activated] in Early stage Severe
      Sepsis) long-term follow-up: one-year safety and efficacy evaluation.
AB  - OBJECTIVE: To demonstrate that drotrecogin alfa (activated) has an acceptable
      safety profile 1 yr from randomization. DESIGN: One-year follow-up of patients
      participating in a placebo-controlled clinical study of drotrecogin alfa
      (activated) in severe sepsis patients at low risk of death (the ADDRESS study).
      SETTING: The study was conducted at 516 hospitals in 34 countries. PATIENTS: The
      study included 2,640 patients. INTERVENTIONS: One-year follow-up was performed as
      an addendum to the placebo-controlled ADDRESS study. Treatment groups were
      compared using the chi-square test and Kaplan-Meier estimates. MEASUREMENTS AND
      MAIN RESULTS: Survival status at 1 yr was obtained for 90% of patients enrolled
      in the study (n = 2,376). The difference in mortality rate between drotrecogin
      alfa (activated) and placebo patients was numerically smaller at 1 yr (34.2% and
      34.0%, respectively, p = .94) than at 28 days (18.5% and 17.0%, respectively, p =
      .34). In the subgroups defined by organ dysfunction class (single or multiple)
      and Acute Physiology and Chronic Health Evaluation II score (<25 or >or=25), the
      differences in mortality rate between treatment groups at 1 yr were consistent
      with those observed at 28 days; no significant differences in mortality rates
      between treatment groups were observed. No additional serious adverse events were
      reported during the period between hospital discharge and 1 yr. CONCLUSIONS: No
      increased risk of death or evidence of harm at 1 yr was associated with
      drotrecogin alfa (activated) administration in patients with severe sepsis at
      lower risk of death.

PMID- 17452936
TI  - Sustained activation of nuclear factor-kappaB by reactive oxygen species is
      involved in the pathogenesis of stress-induced gastric damage in rats.
AB  - OBJECTIVE: Stress ulceration is a common complication in critically ill patients,
      but the mechanisms involved are poorly understood. In this study we investigated
      the temporal activation of the redox-sensitive transcription factor nuclear
      factor-kappaB and its roles in an experimental model of cold immobilization
      stress-induced gastric mucosal lesions. DESIGN: Prospective, controlled, and
      randomized animal study. SETTING: University research laboratory. SUBJECTS: Male
      Sprague-Dawley rats. INTERVENTIONS: The rats were subjected to cold
      immobilization stress for a total of 6 hrs. The temporal profiles of nuclear
      factor-kappaB activation and expression of tumor necrosis factor-alpha,
      interleukin-1beta, cytokine-induced neutrophil chemoattractant-1 (CINC-1),
      intercellular adhesion molecule-1 (ICAM-1), and inducible nitric oxide synthase
      (iNOS) were determined in the gastric corpus mucosa of stressed rats. To study
      the roles of nuclear factor-kappaB activation, rats received an intravenous bolus
      of a specific nuclear factor-kappaB inhibitor Bay 11-7082 (20 mg/kg) 1 hr before
      stress. For antioxidant administration, rats were treated with intravenous
      injection of a free radical scavenger pyrrolidine dithiocarbamate (50, 100, and
      200 mg/kg) 1 hr before stress. MEASUREMENTS AND MAIN RESULTS: Exposure of rats to
      6 hrs of stress led to a rapid and persistent activation of nuclear factor
      kappaB, which was associated with transient degradation of inhibitory protein
      IkappaBalpha and slower but sustained degradation of IkappaBbeta. Nuclear factor
      kappaB activation preceded the induction of tumor necrosis factor-alpha,
      interleukin-1beta, CINC-1, ICAM-1, and iNOS messenger RNAs, all of which were
      linearly increased with the duration of stress. Bay 11-7082 selectively blocked
      the stress-induced nuclear factor-kappaB activation and up-regulation of tumor
      necrosis factor-alpha, interleukin-1beta, CINC-1, ICAM-1, and iNOS messenger
      RNAs. Inhibition of expression of these proinflammatory genes prevented the
      increases in myeloperoxidase activity (an indicator of neutrophil infiltration)
      in gastric mucosa and the development of gastric damage. Pyrrolidine
      dithiocarbamate dose-dependently inhibited the stress-induced nuclear factor
      kappaB pathway activation and consequential proinflammatory gene expression,
      neutrophil infiltration, and gastric damage, suggesting the involvement of
      reactive oxygen species in these processes. CONCLUSIONS: Sustained activation of
      nuclear factor-kappaB by reactive oxygen species is an important in vivo
      mechanism mediating stress-induced gastric inflammatory damage in rats.

PMID- 17452937
TI  - Automatic control of tracheal tube cuff pressure in ventilated patients in
      semirecumbent position: a randomized trial.
AB  - OBJECTIVE: The aspiration of subglottic secretions colonized by bacteria pooled
      around the tracheal tube cuff due to inadvertent deflation (<20 cm H2O) of the
      cuff plays a relevant role in the pathogenesis of ventilator-associated
      pneumonia. We assessed the efficacy of an automatic, validated device for the
      continuous regulation of tracheal tube cuff pressure in preventing ventilator
      associated pneumonia. DESIGN: Prospective randomized controlled trial. SETTING:
      Respiratory intensive care unit and general medical intensive care unit.
      PATIENTS: One hundred and forty-two mechanically ventilated patients (age, 64 +/-
      17 yrs; Acute Physiology and Chronic Health Evaluation II score, 18 +/- 6)
      without pneumonia or aspiration at admission. INTERVENTIONS: Within 24 hrs of
      intubation, patients were randomly allocated to undergo continuous regulation of
      the cuff pressure with the automatic device (n = 73) or routine care of the cuff
      pressure (control group, n = 69). Patients remained in a semirecumbent position
      in bed. MEASUREMENTS AND MAIN RESULTS: The primary end point variable was the
      incidence of ventilator-associated pneumonia. Main causes for intubation were
      decreased consciousness (43, 30%) and exacerbation of chronic respiratory
      diseases (38, 27%). Cuff pressure <20 cm H2O was more frequently observed in the
      control than the automatic group (45.3 vs. 0.7% determinations, p < .001).
      However, the rate of ventilator-associated pneumonia with clinical criteria (16,
      22% vs. 20, 29%) and microbiological confirmation (11, 15% vs. 10, 15%), the
      distribution of early and late onset, the causative microorganisms, and intensive
      care unit (20, 27% vs. 16, 23%) and hospital mortality (30, 41% vs. 23, 33%) were
      similar for the automatic and control groups, respectively. CONCLUSIONS: Cuff
      pressure is better controlled with the automatic device. However, it did not
      result in additional benefits to the semirecumbent position in preventing
      ventilator-associated pneumonia.

PMID- 17452938
TI  - Efficacy of colistin/rifampin combination in experimental rat models of sepsis
      due to a multiresistant Pseudomonas aeruginosa strain.
AB  - OBJECTIVE: To investigate the efficacy of rifampin and colistin in three
      experimental rat models of Pseudomonas aeruginosa sepsis. DESIGN: Prospective,
      randomized, controlled animal study. SETTING: Research laboratory in a university
      hospital. SUBJECTS: Adult male Wistar rats. INTERVENTIONS: Adult male Wistar rats
      were given a) an intraperitoneal injection of 1 mg of P. aeruginosa 10
      lipopolysaccharide; b) 2 x 10(10) colony-forming units of P. aeruginosa ATCC
      27853; and c) 2 x 10(10) colony-forming units of one clinically multiresistant
      strain of P. aeruginosa. For each model, all animals were randomized to receive
      intravenously isotonic sodium chloride solution, 10 mg/kg rifampin, 1 mg/kg
      colistin, and 10 mg/kg rifampin plus 1 mg/kg colistin. MEASUREMENTS AND MAIN
      RESULTS: Lethality, bacterial growth in blood and peritoneum, and endotoxin and
      tumor necrosis factor-alpha concentrations in plasma were measured. Colistin
      exerted a strong antimicrobial activity and achieved a significant reduction of
      plasma endotoxin and tumor necrosis factor-alpha concentration compared with
      control and rifampin-treated groups. Rifampin exhibited no antimicrobial activity
      with no substantial impact on endotoxin and tumor necrosis factor-alpha plasma
      concentrations. The combination of colistin and rifampin resulted in a
      significant reduction in bacterial count compared with colistin monotherapy,
      whereas no significant difference was found in positive hem cultures and
      mortality rates between the two groups. CONCLUSIONS: Colistin and rifampin might
      have a role in the therapy of multiresistant P. aeruginosa infection.

PMID- 17452939
TI  - A systematic review of urinary findings in experimental septic acute renal
      failure.
AB  - OBJECTIVE: In experimental septic acute renal failure, urinary analysis is used
      to help diagnose and classify renal injury. However, the scientific basis for
      such use has not been systematically evaluated. Thus, we appraised the value of
      common urinary findings for the diagnosis and classification of experimental
      septic acute renal failure. DESIGN: Systematic review. SETTING: Academic medical
      center and university-based research laboratory. SUBJECTS: Experimental studies
      describing urinary biochemistry, derived indexes, and microscopy in septic acute
      renal failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Twenty-seven
      articles fulfilled all inclusion criteria. Due to heterogeneity, no formal
      quantitative analysis was possible. The methods for induction of sepsis and
      models were variable. The urinary sodium, fractional excretion of sodium, and
      urine osmolality were reported in only four (15%), 21 (78%), and seven (26%)
      studies, respectively. The fractional excretion of sodium exhibited a decrease,
      no change, or an increase from baseline in 11 (52%), five (24%), and five (24%)
      studies, respectively. The urine osmolality decreased from baseline in all
      endotoxin-induced models but showed an early transient increase in six (22%)
      studies of cecal-ligation perforation. Proteinuria or urinary enzymuria was
      reported in only seven (26%) studies. Urinary microscopy was described in one
      study. Only ten studies (37%) simultaneously reported on histopathology. In all
      these studies, histology either was normal or showed minor ultrastructural
      changes on electron microscopy. CONCLUSIONS: No conclusions are possible on how
      several urinary tests perform in diagnosing or classifying acute renal failure or
      in predicting the presence of acute tubular necrosis in experimental sepsis.
      Additional research is necessary to define the diagnostic and prognostic value of
      urinalysis in experimental sepsis.

PMID- 17452940
TI  - Mechanisms of sepsis-induced cardiac dysfunction.
AB  - OBJECTIVES: To review mechanisms underlying sepsis-induced cardiac dysfunction in
      general and intrinsic myocardial depression in particular. DATA SOURCE: MEDLINE
      database. DATA SYNTHESIS: Myocardial depression is a well-recognized
      manifestation of organ dysfunction in sepsis. Due to the lack of a generally
      accepted definition and the absence of large epidemiologic studies, its frequency
      is uncertain. Echocardiographic studies suggest that 40% to 50% of patients with
      prolonged septic shock develop myocardial depression, as defined by a reduced
      ejection fraction. Sepsis-related changes in circulating volume and vessel tone
      inevitably affect cardiac performance. Although the coronary circulation during
      sepsis is maintained or even increased, alterations in the microcirculation are
      likely. Mitochondrial dysfunction, another feature of sepsis-induced organ
      dysfunction, will also place the cardiomyocytes at risk of adenosine triphosphate
      depletion. However, clinical studies have demonstrated that myocardial cell death
      is rare and that cardiac function is fully reversible in survivors. Hence,
      functional rather than structural changes seem to be responsible for intrinsic
      myocardial depression during sepsis. The underlying mechanisms include down
      regulation of beta-adrenergic receptors, depressed postreceptor signaling
      pathways, impaired calcium liberation from the sarcoplasmic reticulum, and
      impaired electromechanical coupling at the myofibrillar level. Most, if not all,
      of these changes are regulated by cytokines and nitric oxide. CONCLUSIONS:
      Integrative studies are needed to distinguish the hierarchy of the various
      mechanisms underlying septic cardiac dysfunction. As many of these changes are
      related to severe inflammation and not to infection per se, a better
      understanding of septic myocardial dysfunction may be usefully extended to other
      systemic inflammatory conditions encountered in the critically ill. Myocardial
      depression may be arguably viewed as an adaptive event by reducing energy
      expenditure in a situation when energy generation is limited, thereby preventing
      activation of cell death pathways and allowing the potential for full functional
      recovery.

PMID- 17452943
TI  - [DNA microarray technology: principles and applications to the study of
      neurological disorders].
AB  - INTRODUCTION: DNA microarray is a powerful technology which can rapidly provide a
      high throughput and detailed view of the entire genome and transcriptome. In this
      review we discuss the basic principles behind gene expression microarrays, CGH
      arrays and DNA microarray genotyping, and their potential applications to
      neurological diseases. STATE OF THE ART: Microarray gene expression profiling is
      a reliable technology that has already been used with great success in the
      molecular classification of cancer. It is a very promising technology in the
      field of Neurooncology. One of the interesting characteristics of DNA microarrays
      is also that they can be used in a non-hypothesis-driven manner to discover new
      genomic characteristics that will enable to establish new pathophysiological
      hypotheses. Such a strategy has already yielded interesting new insights in the
      study of multiple sclerosis, Alzheimer disease or neuromuscular diseases. With
      DNA microarray genotyping it is now possible to detect mutations in many genes
      simultaneously. CONCLUSIONS: In Neurooncology DNA microarrays should help to
      establish a more accurate classification of brain tumors and recent studies have
      shown how gene expression profiling of brain tumors allows to uncover previously
      unrecognized patient subsets that differ in their survival. The applications of
      microarrays for the study of neurological diseases, like multiple sclerosis,
      Alzheimer disease or neuromuscular diseases are also promising both for
      generating new pathophysiological hypotheses and for enabling new molecular
      classifications. DNA microarray genotyping is a powerful technology that should
      help to discover genetic factors associated with multifactorial neurological
      disorders and help to diagnose complex neurogenetic diseases. This technology
      should also facilitate the realization of pharmacogenomic studies in neurological
      diseases.

PMID- 17452944
TI  - [Oscillopsia: pathophysiological mechanisms and treatment].
AB  - Oscillopsia is an illusion of an unstable visual world. It is associated with
      poor visual acuity and is a disabling and stressful symptom reported by numerous
      patients with neurological disorders. The goal of this paper is to review the
      physiology of the systems subserving stable vision, the various
      pathophysiological mechanisms of oscillopsia and the different treatments
      available. Visual stability is conditioned by two factors. First, images of the
      seen world projected onto the retina have to be stable, a sine qua non condition
      for foveal discriminative function. Vestibulo-ocular and optokinetic reflexes act
      to stabilize the retinal images during head displacements; ocular fixation tends
      to limit the occurrence of micro ocular movements during gazing; a specific
      system also acts to maintain the eyes stable during eccentric gaze. Second,
      although we voluntary move our gaze (body, head and eye displacements), the
      visual world is normally perceived as stable, a phenomenon known as space
      constancy. Indeed, complex cognitive processes compensate for the two sensory
      consequences of gaze displacement, namely an oppositely-directed retinal drift
      and a change in the relationship between retinal and spatial (or subject
      centered) coordinates of the visual scene. In patients, oscillopsia most often
      results from abnormal eye movements which cause excessive motion of images on the
      retina, such as nystagmus or saccadic intrusions or from an impaired vestibulo
      ocular reflex. Understanding the exact mechanisms of impaired eye stability may
      lead to the different treatment options that have been documented in recent
      years. Oscillopsia could also result from an impairment of spatial constancy
      mechanisms that in normal condition compensate for gaze displacements, but
      clinical data in this case are scarce. However, we suggest that some visuo
      perceptive deficits consecutive to temporo-parietal lesions resemble oscillopsia
      and could result from a deficit in elaborating spatial constancy.

PMID- 17452945
TI  - [Phenotypical aspects and clinical course of multiple sclerosis in 76 patients
      with a North African ethnic background followed at the Nice University Hospital].
AB  - AIMS: In the European multiple sclerosis (MS) database registered in Nice, about
      8p.cent of the patients have a North African ethnic background. PATIENTS AND
      METHODS: We performed a descriptive retrospective study of a cohort of 76 MS
      patients with a North African ethnic background followed in the Neurology
      Department of Nice University Hospital. This group was compared with a regional
      MS cohort (n=968) from our EDMUS database. Statistical analysis enabled
      classification of patients into three subgroups which had been submitted to
      different environmental factors according to where they were born and their age
      at immigration. There were prognostic aspects specific to each group. RESULTS:
      Regarding the entire cohort, poor prognostic factors included male gender, onset
      with sequellae, and substantial brain lesions on initial T2-weighted MRI. For the
      subgroups, prognostic aspects specific to each group were: 1) patients of North
      African origin born in France had an early age of onset, delayed diagnosis,
      remission between two long initial expressions of MS, and rapidly developed
      cerebellar problems with a secondary progressive course: 2) patients having
      migrated after age 15 had a late age of onset, delayed diagnosis, remission
      between two short initial expressions of MS, an onset characterized by one
      symptom, which was often a motor symptom involving the spinal cord or brain stem,
      but late-developing cerebellar problems and secondary progressive course are
      frequent; 3) patients having migrated before age 15 had an onset characterized by
      one symptom, often a visual problem, with sequellae and rapid development of
      cerebellar problems. CONCLUSION: The present study was consistent with the more
      unfavorable course of MS in patients of North African ethnic background
      previously reported in the literature. One should distinguish the subgroups to
      improve management of MS. Early administration of treatment should be considered
      for these patients, including earlier and more frequent use of immunosuppressive
      agents.

PMID- 17452946
TI  - [Oligodendroglial defect and insufficiency of remyelination during MS:
      anatomoclinical and experimental comparative study].
AB  - INTRODUCTION: The mechanisms responsible for the failure of remyelination during
      MS are poorly understood. We have analyzed in which way oligodendrocytes (OL)
      could be involved. METHODS: The number of remyelinated fiber per OL has been
      determined in 18 chronic MS lesions and compared to normal appearing white matter
      (NAWM), as well as in the center of lysophosphatidyl choline (LPC)-induced
      lesions in adult rats in which remyelination was accelerated by microinjection of
      neurotrophin-3 (NT-3). RESULTS: In chronic MS lesions and in LPC-induced lesions
      the number of myelinated fibers per OL was strongly decreased compared to NAWM
      and to animals treated with NT-3 respectively. CONCLUSION: Our results suggest
      that the capacity of OL to remyelinate axons could be impaired, due to successive
      relapses, during MS.

PMID- 17452947
TI  - [Use of generic anti-epilepsy drugs in France: survey of neurologists and review
      of the literature].
AB  - INTRODUCTION: The use of generic substitution for antiepileptic drugs is more and
      more frequent but remains controversial. PURPOSE AND METHODS: This survey aimed
      to assess physicians' feelings towards effectiveness, tolerability and clinical
      impact of generic substitution of antiepileptic drugs on their patients. A
      questionnaire was sent to all French private neurologists and hospital
      specialists in epilepsy. Their responses were recorded from December 2005 to
      March 2006. RESULTS: A total of 312 neurologists responded. A few prescribed
      generic antiepileptic drugs; but a few as well indicated not to switch their
      prescription. Most of them felt discomfort by generic substitution. One third
      reported breakthrough seizures or new adverse events after generic substitution
      and 70p.cent extra phone consultation. DISCUSSION: Neurologists' reluctance with
      prescribing generic AEDs may be explained by several different facts: no
      controlled study about the safety and efficacy of generic AEDs as compared with
      brand name drugs, substitutions by pharmacists without their agreement, lack of
      medical information about generic AEDs, symbolic dimension of the treatment, and,
      most of all, the fear of breakthrough seizures in patients good controlled.
      CONCLUSION: A prospective controlled evaluation of the safety and efficacy of
      generic substitution in epilepsy needs to be performed.

PMID- 17452948
TI  - [T-cell lymphoma revealed by a mononeuritis multiplex: case report and review of
      literature].
AB  - INTRODUCTION: Lymphoma occasionally affects the peripheral nervous system.
      Neuropathy usually appears in patients with known lymphoma but rarely represents
      the initial manifestation of underlying malignancy. We report a case in which
      mononeuritis multiplex (MM) was the dominant feature in the clinical presentation
      of a peripheral T-cell non-Hodgkin lymphoma (NHL). OBSERVATION: A 32-year-old man
      suffered from an asymmetric progressive sensory-motor peripheral neuropathy. The
      left peroneal nerve was affected first, then the left median nerve after one
      month, followed by the left trigeminal nerve ten months later. The
      electrophysiological study confirmed the diagnosis of axonal sensory-motor MM.
      Mediastinal adenopathies, splenomegaly, pancytopenia and inflammatory syndrome
      were also found. An osteo-medullary biopsy showed a T-cell NHL. Nerve biopsy
      study found an inflammatory lymphoid infiltration without malignant cell
      supporting the hypothesis of an inflammatory pathogenic process. Chemotherapy
      including cyclophosphamide, hydralazine, vincristine and prednisone were
      administered monthly during 8 months. No improvement was obtained. DISCUSSION: It
      must be emphasised that this case is an uncommon one. On the one hand, NHL is
      rarely associated with MM and on the other hand, it can exceptionally be revealed
      by a MM. We were able to find 30 reported cases of distal neuropathy revealing a
      NHL including, 8 mononeuritis simplex, 9 MM and 13 polyneuropathies.
      Polyradiculoneuritis cases were excluded from this study because the neuropathy
      is usually caused by a meningeal infiltration. The neuropathy was in the majority
      of the cases chronic and axonal. The lymphoma was more often B-cell than T-cell.
      The B-cell lymphoma was frequently associated with a poor prognosis. All
      mechanisms were present with a predominance of neurolymphomatosis.

PMID- 17452949
TI  - [Neurosarcoidosis treated with mycophenolate mofetil: two cases].
AB  - INTRODUCTION: Neurosarcoidosis is a rare (5 cases for one million) immune
      mediated disease generally observed in young adults. Neurological symptoms are
      present in the half of patients, and symptoms remain limited to neurological
      system in 10p.cent. Histological criteria are mandatory to prove the diagnosis.
      The sensitivity and complications of biopsy are variable. The best sensitivity
      appears to be achieved with muscle biopsies which in addition have a lower risk
      of complications. Neurosarcoidosis is usually treated with corticosteroid therapy
      and immunosuppressive drugs (cyclophosphamide, cyclosporine, aziathoprine,
      methotrexate), but frequently resists standard schedules. In addition the many
      contraindications, side effects and cumulated toxicities of immunosuppressive
      drugs compromises their use. Knowledge of the effectiveness of other treatments
      would therefore be useful. Mycophenolate mofetil (MMF) has been used for
      treatment of many immune-mediated neurological diseases, like polymyositis,
      multifocal motor neuropathy, myasthenia or chronic inflammatory demyelinating
      polyradiculoneuropathy. MMF is efficient and well tolerated, but there is no case
      report about neurosarcoidosis. CASE REPORT: We report two observations of young
      patients (14 and 27 years) with a diagnosis of resistant neurosarcoidosis treated
      with MMF (2 g/j) and corticosteroids. A significant and rapid effectiveness was
      clinically and radiologically observed, with good clinical and hematologic
      tolerance. CONCLUSION: The MMF seems to be an interesting rescue treatment for
      neurosarcoidosis. Further evaluation is needed.

PMID- 17452950
TI  - [Familial spastic paraplegia with severe amyotrophy of the hands. (Silver
      syndrome?)].
AB  - Familial spastic paraplegia (FSP) with severe muscular atrophy of hands and feet
      is exceptional. Autosomal dominant forms were initially described by Silver in
      1966. We report two cases, from the same Tunisian family, presenting FSP with
      severe amyotrophy of the hands. A brother and his sister, aged respectively 37
      and 36 years old, presented practically the same clinical picture. Their parents
      were cousins. The female patient was hospitalized. Both patients developed gait
      disorders around the age of three years. Muscular atrophy of the hands arose much
      later, around the age of 20 years. The neurological examination disclosed a
      spastic gait with distal amyotrophy, severe in the hands and moderate in the
      feet. Sensitivity was preserved and there was no fasciculation. The spinal cord
      and cerebral MRI was normal. Electromyography (EMG) showed a neurogenic pattern
      in the distal muscles. Stimulation of the median, ulnar and sciatica nerves was
      ineffective. The somatosensory evoked potentials (EP) were delayed (upper limb)
      or desynchronised (lower limb). The auditory and visual EP were normal. The
      cerebrospinal fluid contained 1 mononuclear cell/mm3 and 10 mg protein/100 ml.
      Abnormalities of the cranio-vertebral junction, Arnold-Chiari malformation,
      syringomyelia and familial juvenile amyotrophic lateral sclerosis (ALS) were
      excluded and the diagnosis of Silver's syndrome was evoked.

PMID- 17452951
TI  - [Electrophysiological aspects of intermediate syndrome in organophosphate
      poisonings].
AB  - Acute organophosphate poisoning, whether accidental or suicidal, is frequent in
      developing countries and produces significant morbidity and mortality.
      Organophosphates inhibit cholinesterase activity at the neuromuscular junction
      and cause extensive muscle paralysis, particularly for respiratory function.
      Poisonings evolve in three stages: cholinesterase crisis, intermediate syndrome
      and delayed neuropathy. Electrophysiological aspects have been poorly studied. We
      report the case of a 25-year-old woman admitted to intensive care unit with
      muscarinic signs and respiratory failure after attempted suicidal organophosphate
      poisoning. Cholinesterase activity was low and the electrophysiological study
      disclosed the characteristic aspect of intermediate syndrome. The patient died
      due to septic complications. This syndrome is exceptional with a poorly
      understood pathophysiology. The electrophysiological study is essential for
      diagnosis.

PMID- 17452952
TI  - [Radiological diagnosis of a lipoma in the posterior fossa].

PMID- 17452953
TI  - [Do chorea and ballism constitute poles of a symptom continuum?].

PMID- 17452954
TI  - Burning mouth syndrome and personality profiles.
AB  - AIM: The burning mouth syndrome (BMS) is an oral disorder that consists of a
      burning pain in the mouth without any visible clinical manifestations: its
      etiology is still unclear and the etiological factors have been classified as
      local, systemic and psychogenic. In this study, we reported the evaluation of the
      psychological profile of BMS and non-BMS subjects in order to identify any
      psychological disease affecting these patients and to evaluate a possible
      psychological factor in the ethiopathogenesis of BMS. METHODS: Twenty-eight
      patients affected by BMS, evaluated at the Section of Dentistry of the University
      of Parma, and 24 matched control subjects were evaluated for their personality
      profile using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), a
      questionnaire which analyses various aspects of personality through 10 scales:
      hypochondriasis, depression, hysteria, psychopathic deviation, masculinity
      femininity, paranoia, psychasthenia, schizophrenia, hypomania, social
      introversion. From this study, 7 BMS patients and 12 control subjects were
      excluded due to high scores reported in one or more of the 3 control scales. The
      t-test and the Mann-Whitney test were used to compare the 2 groups and the
      results were considered statistically significant with P<0.01. RESULTS: The
      results show no significant differences in personality profiles between the BMS
      and the control subjects suggesting an etiology for BMS different from the
      psychogenic hypothesis. CONCLUSIONS: Further researches and the evaluation of
      larger BMS subjects groups are necessary in order to validate the hypothesis of
      the neurological etiology of BMS.

PMID- 17452955
TI  - Periodontal pathogens in periodontal pockets and in carotid atheromatous plaques.
AB  - AIM: In the last years the relationship between periodontitis and cardiovascular
      diseases has been a subject of increasing research. The identification of
      periodontopathic bacteria in atheromas can contribute to our knowledge of such an
      association. The aim of our study was to assess the concomitant presence of 5
      periodontal pathogens (Actinobacillus actinomycetemcomitans, Prevotella
      intermedia, Porphyromonas gingivalis, Treponema denticola, and Tannerella
      forsythia) in periodontal pockets and in carotid atheromas recovered from the
      same individuals. METHODS: Twenty-one patients with chronic periodontitis
      scheduled for endarterectomy for carotid stenosis were enrolled in the study.
      Subgingival plaque samples and carotid atheromas were examined using the
      polymerase chain reaction and reverse hybridization techniques by means of
      specific probes for periodontal bacteria. Human beta-globin amplification was
      used as internal polymerase chain reaction efficiency control. RESULTS: Three
      patients were excluded because the endarterectomy specimens were negative to DNA
      amplification. All subgingival plaque samples were positive for at least one
      target micro-organism. The prevalence of Tannerella forsythia, Porphyromonas
      gingivalis, Prevotella intermedia, Treponema denticola, and Actinobacillus
      actinomycetemcomitans was 72.22%, 61.11%, 55.56%, 50%, and 33.33%, respectively.
      No periodontal bacteria DNA was detected in any endarterectomy specimen.
      CONCLUSIONS: The presence of periodontal bacteria in atheromatous plaques was not
      confirmed by this investigation and, thus, no correlation between periodontitis
      bacteria and micro-organisms involved in the atherosclerotic lesions could be
      drawn.

PMID- 17452956
TI  - Treatment of severe bilateral temporomandibular joint ankylosis in adults: our
      protocol.
AB  - AIM: In order to evaluate the reliability of interpositional gap arthroplasty
      with temporalis myofascial flap the authors retrospectively analysed the data of
      5 patients suffering from bilateral temporomandibular ankylosis operated on with
      this technique. METHODS: The preoperative assessment included evaluation of pain
      during function, interference with eating and the maximal interincisal distance.
      All patients received bony ankylosis removal, interposition of a finger-shaped
      temporalis myofascial flap in the articular gap and coverage with temporoparietal
      fascial flap as a new capsule. In the postoperative period an aggressive
      physiotherapy was carried on for at least 6 months. RESULTS: All cases
      experimented release of pain (evaluated by a Visual Analogue Scale method), a
      return to a normal diet and a stable improvement in mouth opening during the
      follow-up period. CONCLUSIONS: This technique should be considered a reliable
      method to avoid relapse of ankylosis and to stabilize postoperative results.

PMID- 17452957
TI  - Professional clinical bleaching with Pola Office: 6-month clinical results with
      spectrophotometric analysis.
AB  - AIM: The aim of the study was to evaluate the efficacy of the professional
      bleaching treatment with Pola Office (SDI): the shade, chroma and value
      parameters of the anterior upper elements were analysed. METHODS: At the
      Prosthetic Unit of the Modena and Reggio Emilia University, 10 patients were
      selected. All patients underwent oral hygiene treatment and spectrophotometric
      analysis (Spectro-Shade) of the 6 front elements: the variables L (value), c
      (chroma), and h (shade) were examined in the cervical, mesial and incisal
      sections. Spectrophotometric analysis was repeated 6 months after initial
      bleaching. The patients were asked to report the degree of sensitivity after 3,
      6, 12 and 24 h and after 3, 6, 7, and 10 days. RESULTS: The value (L) of the
      treated elements increases after bleaching, the chroma parameter (c) showed lower
      values than those prior to treatment (except for the first patient); this means a
      shift towards a lower degree of saturation. The course of the shade parameter is
      uniform and constant for all patients, with a shift towards yellow chroma values.
      Postoperative sensitivity was confined to the first 3 h after treatment, after
      which it showed a steady decrease over 24 h. CONCLUSIONS: Esthetic results
      obtained using the Pola Office bleaching procedure were visibly significant;
      confirmed by colorimeter analysis. The harmony between chroma, shade and value
      remained 6 months after the bleaching treatment; the sensitivity is particularly
      high in the first hour, however after 24 h sensitivity is greatly reduced.

PMID- 17452958
TI  - Analysis of the diametral compressive bond strength between composite resin and
      amalgam in different stages of oxidation.
AB  - AIM: Amalcomp is a technique that combines composite resin to amalgam in
      restorative procedures to improve esthetics and minimize the negative effects of
      polymerization on dental tissues. The objective of this in vitro study was to
      measure the diametral compressive bond strength between Fill Magic composite
      (Vigodent) versus Permite (DFL) or Velvalloy (SS White) amalgams in different
      oxidation stages. METHODS: Twenty-four cylinders of each amalgam brand were
      fabricated using a Teflon matrix and divided into 3 groups according to the
      immersion period in artificial saliva for oxidation: A (1 day), B (7 days) and C
      (30 days). After immersion, the amalgam cylinders were bonded to the composite
      specimens using the Scotch Bond Multi Use Plus (3M) bonding system. Diametral
      compression assays were then carried out in an EMIC-MEM 2000 universal testing
      machine set to 0.5 mm/min. Statistical analysis was performed using ANOVA and
      Tukey's test. RESULTS: The mean recorded strength (MPa) for each oxidation group
      was: A=9.71, B=8.21 and C=6.98 (A>B = C; P<0.01). Permite (7.24) provided
      significantly less adhesion to the composite than Velvalloy (9.36; P<0.05). There
      was no interaction between the factors alloy, resin and time. CONCLUSIONS: Under
      the conditions of this study, the less oxidized amalgam showed the greatest
      diametral compressive strength values.

PMID- 17452959
TI  - Pemphigus vulgaris: recent advances in our understanding of its pathogenesis.
AB  - Pemphigus, a group of bullous diseases affecting the oral mucosa and the skin, is
      caused by antibody-mediated autoimmune reaction to desmogleins (Dsg), desmosomal
      transmembrane glycoproteins, leading to acantholysis. Pemphigus is classified
      into pemphigus vulgaris (PV), with suprabasal acantholysis, and pemphigus
      foliaceus (PF), with acantholysis in the more superficial epidermis. Pemphigus
      vulgaris is characterized by IgG autoantibodies against desmoglein 3 (Dsg 3),
      whereas the target of PF is Dsg1, although about 50% of PV patients also have
      Dsg1 autoantibodies. The clinical phenotype appears to be determined by the
      distribution of Dsg1 and Dsg3. PV patients with oral mucosal lesions have
      predominantly Dsg3 autoantibodies. Lesion distribution is related to the location
      of the antigen (Dgs 3 and/or Dgs 1) in the epithelium and specific autoantibody
      production. Coexpression of Dsg 1 and Dsg 3 in keratinocytes protects against
      blister formations in the presence of antibodies against only one of the two
      desmogleins. Recent molecular studies have shown that acantholysis can occur also
      in the presence of antibodies against 9 alpha nicotinic acetylcholine receptor
      (AChR). Cholinergic agonists can protect keratinocyte monolayers against anti-Dsg
      antibody-induced acantholysis and reverse acantholysis produced by PV IgGs.

PMID- 17452960
TI  - Male breast cancer with mandibular metastasis. A case report.
AB  - Female breast cancer is one of the major causes of death among women while male
      breast cancer is relatively uncommon and accounts for about 1% of all breast
      cancers in both sexes. Influencing factors are: gynecomasty, familiarity for male
      breast cancer, Jewish and African-American male population. From the histological
      point of view, it is not different from the female breast cancer, except for the
      infiltrant ductal carcinoma, but with a much severe prognosis. Breast cancer
      metastases to the jaws are rare, only 1%; the most common sites of metastases
      are: lungs(59-69%), liver (58-65%), bone (44-71%), pleura (23-37%), brain (9-22%)
      and kidney (4-17%). At present, based on a literature research (May 2006), there
      have been just two other case reports of male breast cancer metastasis to the
      maxillofacial region, both to the mandible. The case of a 69-year-old white man
      who in 2001 underwent a radical mastectomy due to ductal breast cancer is
      reported. In 2005 the patient was referred to our department by his oncologist
      for multiple oral fistula. A mandibular TC revealed osteolytic lesions and the
      patient underwent mandibular surgery to remove the lesions and clean up the area.
      The histological examination was consistent with that of a metastatic deposit of
      adenocarcinoma of the breast. In June 2006 the patient died due to worsening of
      the general clinical conditions, in particular due to ascites and hepatic
      insufficiency.

PMID- 17452961
TI  - Kirschner wire as a guide to secondary reconstruction of the deformities of the
      zygoma. A technical note.
AB  - Mistreated fractures of the zygomatic complex may result in facial enlargement,
      loss of zygomatic projection, increase of orbitary volume, diplopy, enophthalmy,
      neuropraxy of the infraorbitary nerve and limited mouth opening. Hence, the
      treatment of sequelae demands accurate planning, through approaches that evaluate
      the degree of the existing displacement, bone repositioning and the need of
      grafts. Surgery is difficult due to lack of anatomical references as guides for
      bone repositioning. Some techniques have been described in the literature as
      alternatives for evaluating the degree of bone displacement and necessary
      correction. We believe that a greater number of anatomical references may
      contribute to a better final result. The aim of this paper is to present a simple
      technique using three Kirschner wires as spacial parameters-guides that aid
      secondary reconstructions of fractures of the zygomatic complex. After osteotomy,
      it becomes possible to compare and transfer the measures of the non-affected bone
      for re-establishing an adequate anatomical position for the affected side. This
      approach is proposed as a useful tool for obtaining 3-D references, helping to
      obtain a better bone positioning.

PMID- 17452962
TI  - Is pramlintide a safe and effective adjunct therapy for patients with type 1
      diabetes?

PMID- 17452964
TI  - Pheochromocytoma-quo vadis?

PMID- 17452965
TI  - The participation of children in nontherapeutic diabetes research in the US.

PMID- 17452966
TI  - Management of Graves' ophthalmopathy.
AB  - Management of Graves' ophthalmopathy is preferably done in a multidisciplinary
      setting. Smoking is associated with worse disease outcome. (131)I therapy for
      hyperthyroidism can also worsen ophthalmopathy, especially if administered during
      active disease or to patients who smoke or have severe hyperthyroidism, or those
      with high levels of TSH-receptor-binding inhibitory immunoglobulins.
      Coadministration of steroids and (131)I therapy is recommended for such high-risk
      patients. (131)I therapy is safe for patients with inactive Graves'
      ophthalmopathy. Subtotal thyroidectomy and antithyroid drugs show no benefit or
      harm to eye changes. There is no good evidence that total thyroid ablation has
      additional benefit. Artificial teardrops, dark glasses and prisms are very
      helpful. Dysthyroid optic neuropathy is best treated with intravenous pulsed
      methylprednisolone; if visual functions do not recover, urgent surgical
      decompression is indicated. A wait-and-see policy is recommended in mild Graves'
      ophthalmopathy because the natural history of this condition reveals a tendency
      to resolve spontaneously. Active, moderately severe Graves' ophthalmopathy
      qualifies for immunosuppression: intravenous pulsed methylprednisolone is more
      efficacious and has fewer side effects than oral steroids. Once the disease is
      inactive, rehabilitative surgery has much to offer. Quality of life is seriously
      limited in patients with Graves' ophthalmopathy, and remains restricted even
      after all treatments. Consequently, there is an urgent need for improved
      treatment modalities, and antibody therapy has shown promise in this respect.

PMID- 17452967
TI  - Prenatal diagnosis and treatment of congenital adrenal hyperplasia owing to 21
      hydroxylase deficiency.
AB  - Classical forms of congenital adrenal hyperplasia are caused by a severe
      deficiency of 21-hydroxylase, an enzyme involved in steroid biosynthesis, which
      triggers excessive androgen production before birth. Affected females experience
      virilization both physically and psychologically. Prenatal diagnosis and
      treatment of congenital adrenal hyperplasia has been implemented for more than 20
      years. In utero gene-specific diagnosis is now feasible for fetal cell samples
      derived from chorionic villi or amniotic cells in culture, and this gene-specific
      diagnosis guides the treatment of the affected female fetus. Appropriate
      dexamethasone administration to the at-risk pregnant mother is effective in
      reducing genital virilization in the fetus, and thus avoids unnecessary
      genitoplasty in affected females. Current data from large human studies show the
      benefit and safety of prenatal treatment. Long-term follow-up of the safety of
      prenatal treatment is currently underway. This practice is a rare example of
      effective prenatal treatment to prevent a malformation caused by an inborn error
      of metabolism.

PMID- 17452968
TI  - Recognizing rare disorders: aromatase deficiency.
AB  - Aromatase deficiency is rare in humans. Affected individuals cannot synthesize
      endogenous estrogens. Aromatase is the enzyme that catalyzes conversion of
      androgens into estrogens, and if aromatase is nonfunctional because of an
      inactivating mutation, estrogen synthesis cannot occur. If the fetus lacks
      aromatase activity, dehydroepiandrosterone sulfate produced by the fetal adrenal
      glands cannot be converted to estrogen by the placenta, so is converted to
      testosterone peripherally and results in virilization of both fetus and mother.
      Virilization manifests as pseudohermaphroditism in female infants, with hirsutism
      and acne in the mother; the maternal indicators resolve following delivery. To
      date, only seven males and seven females with aromatase deficiency have been
      reported. Affected females are typically diagnosed at birth because of the
      pseudohermaphroditism. Cystic ovaries and delayed bone maturation can occur
      during childhood and adolescence in these girls, who present at puberty with
      primary amenorrhea, failure of breast development, virilization, and
      hypergonadotrophic hypogonadism. Affected males, on the other hand, do not
      present with obvious defects at birth, so are diagnosed much later in life,
      presenting with clinical symptoms, which include tall stature, delayed skeletal
      maturation, delayed epiphyseal closure, bone pain, eunuchoid body proportions and
      excess adiposity. Estrogen replacement therapy reverses the symptoms in male and
      female patients.

PMID- 17452969
TI  - Mechanisms of Disease: molecular genetics of childhood thyroid cancers.
AB  - Childhood thyroid cancers are uncommon and have a fairly good prognosis.
      Papillary adenocarcinoma is the most prevalent malignant tumor of the thyroid in
      children and adults with radiation-induced or sporadic cancer. The incidence of
      thyroid cancer in children increased dramatically in the territories affected by
      the Chernobyl nuclear accident; this increase is probably attributable to (131)I
      and other short-lived isotopes of iodine released into the environment. There was
      a broad range of latency periods in children who developed thyroid cancer; some
      periods were less than 5 years. The mutational spectrum of childhood thyroid
      cancers demonstrates that gene rearrangements that lead to the activation of
      mitogen-activated protein kinase signaling seem to have a pivotal role; point
      mutations are rare. So far none of the cancer genes or tumor suppressors, or a
      peculiar gene expression pattern, has been specifically implicated in radiation
      induced thyroid carcinogenesis. The frequency of certain oncogenes does, however,
      vary in tumors that develop after different periods of latency. Such differences
      in the distribution of gene abnormalities in radiation-related cancers implies
      that they associate with patients' age at exposure and diagnosis,
      clinicopathological manifestations of disease and depend on an individual's
      genetic characteristics. Here we review results of pathological and molecular
      studies in childhood thyroid cancer.

PMID- 17452970
TI  - A treatment strategy for Graves' orbitopathy.
AB  - BACKGROUND: A 59-year-old woman with a history of nodular goiter developed
      thyrotoxic symptoms while on levothyroxine therapy. Her thyrotoxicosis persisted
      after levothyroxine withdrawal, so she was given methimazole and, once euthyroid,
      underwent near-total thyroidectomy. Histological examination revealed a nodular
      variant of Graves' disease. Proptosis, eyelid swelling and diplopia appeared 2
      months after surgery. These symptoms worsened, and the patient was initially
      given four intravenous pulses of glucocorticoids, which resulted in a transient
      amelioration of her eye symptoms. After glucocorticoid withdrawal, however, the
      patient's eye motility worsened and there was a reduction of visual acuity in the
      left eye. She was then referred to our hospital for further advice and treatment.
      INVESTIGATIONS: Complete thyroid and ophthalmological evaluation, computerized
      visual field analysis, CT scan of the orbits, routine blood tests, search for
      occult fecal blood, blood tests for hepatitis B and C virus markers, measurements
      of serum non-organ-specific autoantibodies and serum anti-TSH-receptor
      antibodies, and liver ultrasonography. DIAGNOSIS: Nodular Graves' disease with
      severe, active Graves' orbitopathy complicated by optic neuropathy. MANAGEMENT:
      Intravenous glucocorticoid therapy for 3 consecutive days, followed by once
      weekly pulses of intravenous glucocorticoids over a 10-week period, and then by
      oral prednisone treatment on alternate days for 2 months. During the first 2
      weeks of intravenous glucocorticoid therapy the patient received orbital
      irradiation. Therapy resulted in optimized visual acuity and a moderate
      improvement of soft-tissue inflammatory signs and symptoms, whereas proptosis and
      eye motility improved only slightly. The patient is now scheduled for orbital
      decompression and rehabilitative surgery.

PMID- 17452971
TI  - A second-generation profiling system for quantitative methylation analysis of
      multiple gene promoters: application to lung cancer.
AB  - Cancer-specific gene promoter methylation has been described in many types of
      cancers, and various semi-quantified results have shown their usefulness. Here,
      we show a more sensitive and specific second-generation system for profiling the
      DNA methylation status. This method is based on bisulfite reaction of DNA and
      real-time PCR using two TaqMan MGB probes labeled with different fluorescence,
      followed by clustering analysis. Primers were designed with CpG-less sequences,
      and TaqMan MGB probes were designed to contain three or four CpG sites and to be
      shorter than conventional TaqMan probes. We have added new criteria for primer
      and probe design for further specificity. We confirmed the reliability of this
      system and applied it to analysis of lung cancers. Using 10 promoters, 90 primary
      lung cancers were clustered into six groups consisting of cases having similar
      smoking status and pathological findings. EGFR mutation and p16 promoter DNA
      methylation were exclusive, as previously reported; however, DNA methylation in
      other genes was unrelated to EGFR mutation. This system was also useful to
      distinguish double primary lung cancers from a single cancer with intrapulmonary
      metastasis. As above, our system has widespread availability in clinical use and
      biological research.

PMID- 17452972
TI  - Antizyme1 mediates AURKAIP1-dependent degradation of Aurora-A.
AB  - Overexpression of Aurora-A oncogene has been shown to induce genomic instability
      and tumorigenesis. Cellular levels of Aurora-A are regulated by multiple
      mechanisms including the proteasome-dependent degradation of Aurora-A protein.
      Cell-cycle-dependent turnover of Aurora-A protein is mediated by cdh1 through
      ubiquitin (Ub)- and proteasome-dependent pathway. However, Aurora-A kinase
      interacting protein 1 (AURKAIP1), a negative regulator of Aurora-A, also promotes
      proteasome-dependent Aurora-A degradation through an Ub-independent mechanism. In
      an attempt to understand how AURKAIP1 promotes Aurora-A degradation through Ub
      independent pathway, we demonstrate here that antizyme1 (Az1), a well-studied
      mediator of Ub-independent protein degradation pathway, regulates Aurora-A
      protein stability. We show that ectopic or polyamine-induced expression of Az1
      can lower the steady-state levels of Aurora-A. The effect of Az1 on Aurora-A
      turnover was shown to be proteasome-dependent, but Ub-independent. Az1 interacts
      with Aurora-A in vivo and the interaction between Aurora-A and Az1 is essential
      for the Az1-mediated Aurora-A degradation. Furthermore, we observed that AURKAIP1
      could not promote degradation of Aurora-A mutant, which is defective in Az1
      interaction. Coexpression of the Az inhibitor (AzI), which downregulates Az1
      functions, also abrogated AURKAIP1-mediated degradation of Aurora-A. We further
      demonstrated that AURKAIP1, Az1 and Aurora-A could exist as a ternary complex and
      AURKAIP1 enhances the interaction between Az1 and Aurora-A. We propose that
      AURKAIP1 might function upstream of the Az1 by enhancing the binding affinity of
      Az1 to Aurora-A to promote recognition, targeting to proteasome and subsequent
      degradation.

PMID- 17452973
TI  - Interferon regulatory factor-1-induced apoptosis mediated by a ligand-independent
      fas-associated death domain pathway in breast cancer cells.
AB  - Interferon (IFN) regulatory factor-1 (IRF-1) is a transcription factor that has
      apoptotic anti-tumor activity. In breast cancer cell types, IRF-1 is implicated
      in mediating apoptosis by both novel and established anti-tumor agents, including
      the anti-estrogens tamoxifen and faslodex. Here we demonstrate that in MDA468
      breast cancer cells, apoptosis by IFN-gamma is mediated by IRF-1 and IFN-gamma,
      and IRF-1-induced apoptosis is caspase-mediated. IRF-1 induction results in
      cleavage of caspase-8, -3 and -7, and application of caspase inhibitors attenuate
      activated cleavage products. IRF-1-induced apoptosis involves caspase-8 since
      apoptosis is significantly decreased by the caspase-8-specific inhibitor IETD, c
      FLIP expression and in caspase-8-deficient cancer cells. Furthermore, we
      demonstrate that IRF-1-induced apoptosis requires fas-associated death domain
      (FADD) since dominant-negative FADD expressing cells resist IRF-1-induced
      apoptosis and activated downstream products. Immunofluorescent studies
      demonstrate perinuclear colocalization of FADD and caspase-8. Despite the known
      role of FADD in mediating death-ligand induced apoptosis, neutralizing antibodies
      against classical death receptors do not inhibit IRF-1 induced apoptosis, and no
      secreted ligand appears to be involved since MDA468 coincubated with IRF-1
      transfected cells do not apoptose. Therefore, we demonstrate that IRF-1 induces a
      ligand-independent FADD/caspase-8-mediated apoptosis in breast cancer cells.

PMID- 17452974
TI  - Gadd45a regulates beta-catenin distribution and maintains cell-cell
      adhesion/contact.
AB  - Gadd45a, a growth arrest and DNA-damage gene, plays important roles in the
      control of cell cycle checkpoints, DNA repair and apoptosis. We show here that
      Gadd45a is involved in the control of cell contact inhibition and cell-cell
      adhesion. Gadd45a can serve as an adapter to enhance the interaction between beta
      catenin and Caveolin-1, and in turn induces beta-catenin translocation to cell
      membrane for maintaining cell-cell adhesion/contact inhibition. This is coupled
      with reduction of beta-catenin in cytoplasm and nucleus following Gadd45a
      induction, which is reflected by the downregulation of cyclin D1, one of the beta
      catenin targeted genes. Additionally, Gadd45a facilitates ultraviolet radiation
      induced degradation of cytoplasmic and nuclear beta-catenin in a p53-dependent
      manner via activation of p38 kinase. These findings define a novel link that
      connects Gadd45a to cell-cell adhesion and cell contact inhibition, which might
      contribute to the role of Gadd45a in inhibiting tumorigenesis.

PMID- 17452975
TI  - Loss of suppressor-of-fused function promotes tumorigenesis.
AB  - The Sonic Hedgehog (SHH) signaling pathway is indispensable for development, and
      functions to activate a transcriptional program modulated by the GLI
      transcription factors. Here, we report that loss of a regulator of the SHH
      pathway, Suppressor of Fused (Sufu), resulted in early embryonic lethality in the
      mouse similar to inactivation of another SHH regulator, Patched1 (Ptch1). In
      contrast to Ptch1+/- mice, Sufu+/- mice were not tumor prone. However, in
      conjunction with p53 loss, Sufu+/- animals developed tumors including
      medulloblastoma and rhabdomyosarcoma. Tumors present in Sufu+/-p53-/- animals
      resulted from Sufu loss of heterozygosity. Sufu+/-p53-/- medulloblastomas also
      expressed a signature gene expression profile typical of aberrant SHH signaling,
      including upregulation of N-myc, Sfrp1, Ptch2 and cyclin D1. Finally, the
      Smoothened inhibitor, hedgehog antagonist, did not block growth of tumors arising
      from Sufu inactivation. These data demonstrate that Sufu is essential for
      development and functions as a tumor suppressor.

PMID- 17452976
TI  - Involvement of upregulation of DEPDC1 (DEP domain containing 1) in bladder
      carcinogenesis.
AB  - In an attempt to disclose mechanisms of bladder carcinogenesis and discover novel
      target molecules for development of treatment, we applied a cDNA microarray to
      screen genes that were significantly transactivated in bladder cancer cells.
      Among the upregulated genes, we here focused on a novel gene, (DEPDC1) DEP domain
      containing 1, whose overexpression was confirmed by northern blot and
      immunohistochemical analyses. Immunocytochemical staining analysis detected
      strong staining of endogenous DEPDC1 protein in the nucleus of bladder cancer
      cells. Since DEPDC1 expression was hardly detectable in any of 24 normal human
      tissues we examined except the testis, we considered this gene-product to be a
      novel cancer/testis antigen. Suppression of DEPDC1 expression with small
      interfering RNA significantly inhibited growth of bladder cancer cells. Taken
      together, these findings suggest that DEPDC1 might play an essential role in the
      growth of bladder cancer cells, and would be a promising molecular-target for
      novel therapeutic drugs or cancer peptide-vaccine to bladder cancers.

PMID- 17452977
TI  - The LIM-only factor LMO4 regulates expression of the BMP7 gene through an HDAC2
      dependent mechanism, and controls cell proliferation and apoptosis of mammary
      epithelial cells.
AB  - The nuclear LIM-only protein 4 (LMO4) is upregulated in breast cancer, especially
      estrogen receptor-negative tumors, and its overexpression in mice leads to
      hyperplasia and tumor formation. Here, we show that deletion of LMO4 in the
      mammary glands of mice leads to impaired lobuloalveolar development due to
      decreased epithelial cell proliferation. With the goal of discovering potential
      LMO4-target genes, we also developed a conditional expression system in MCF-7
      cells for both LMO4 and a dominant negative (DN) form of its co-regulator,
      cofactor of LIM domains (Clim/Ldb/Nli). We then used DNA microarrays to identify
      genes responsive to LMO4 and DN-Clim upregulation. One of the genes common to
      both data sets was bone morphogenic protein 7 (BMP7), whose expression is also
      significantly correlated with LMO4 transcript levels in a large dataset of human
      breast cancers, suggesting that BMP7 is a bona fide target gene of LMO4 in breast
      cancer. Inhibition of BMP7 partially blocks the effects of LMO4 on apoptosis,
      indicating that BMP7 mediates at least some functions of LMO4. Gene transfer
      studies show that LMO4 regulates the BMP7 promoter, and chromatin
      immunoprecipitation studies show that LMO4 and its cofactor Clim2 are recruited
      to the BMP7 promoter. Furthermore, we demonstrate that HDAC2 recruitment to the
      BMP7 promoter is inhibited by upregulation of LMO4 and that HDAC2 knockdown
      upregulates the promoter. These studies suggest a novel mechanism of action for
      LMO4: LMO4, Clim2 and HDAC2 are part of a transcriptional complex, and increased
      LMO4 levels can disrupt the complex, leading to decreased HDAC2 recruitment and
      increased promoter activity.

PMID- 17452978
TI  - KIT oncoprotein interactions in gastrointestinal stromal tumors: therapeutic
      relevance.
AB  - Most gastrointestinal stromal tumors (GISTs) express oncogenic and constitutively
      active forms of the KIT or platelet-derived growth factor receptor alpha (PDGFRA)
      receptor tyrosine kinase proteins, and these kinase oncoproteins serve as targets
      for effective therapies. Given that mutant KIT oncoproteins serve crucial
      transforming roles in GISTs, we evaluated interactions with the KIT oncoproteins
      and determined signaling pathways that are dependent on KIT oncogenic activation
      in GISTs. Tyrosine-phosphorylated KIT oncoproteins interacted with PDGFRA,
      PDGFRB, phosphatidylinositol 3-kinase (PI3-K) and PKCtheta in GIST cells, and
      these interactions were abolished by KIT inhibition with imatinib or PKC412 or
      KIT RNAi. Notably, tyrosine-phosphorylated PDGFRA was prominent in frozen GIST
      tumors expressing KIT oncoproteins, suggesting that KIT-mediated PDGFRA
      phosphorylation is an efficient and biologically consequential mechanism in
      GISTs. Activated signaling intermediates were identified by immunoaffinity
      purification of tyrosine-phosphorylated proteins in GIST cells before and after
      treatment with KIT inhibitors, and these analyses show that GRB2, SHC, CBL and
      MAPK activation are largely KIT dependent in GISTs, whereas PI3-K, STAT1 and
      STAT3 activation are partially KIT dependent. In addition, we found that
      phosphorylation of several tyrosine kinase proteins - including JAK1 and EPHA4 -
      did not depend on KIT activation. Likewise, paxillin activation was independent
      of the KIT oncogenic signal. These studies identify signaling pathways that can
      provide both KIT-dependent and KIT-independent therapeutic synergies in GIST, and
      thereby highlight clinical strategies that might consolidate GIST therapeutic
      response to KIT/PDGFRA inhibition.

PMID- 17452979
TI  - An osteopontin fragment is essential for tumor cell invasion in hepatocellular
      carcinoma.
AB  - Tumor cell invasion is a primary event in the metastatic progression of
      hepatocellular carcinoma (HCC). Our recent results indicate a concordant elevated
      expression of osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) in primary
      metastatic HCC. This study hypothesizes an MMP-9-directed cleavage of OPN that
      biologically contributes to HCC metastasis. We found that MMP-9 cleaved OPN into
      specific fragments in vitro, of which three could be identified by Edman
      degradation amino-acid sequencing. One of these fragments (OPN-5 kDa, residues
      167-210) induced low-metastatic HCC cellular invasion via CD44 receptors, which
      was effectively blocked by the addition of small peptides within the region of
      OPN-5 kDa. Increased expression of an OPN splice variant (OPN-c) was associated
      with clinical metastatic HCC. Overexpression of OPN-c with physiological levels
      of MMP-9 enhanced cellular invasion and coincided with elevated OPN-5 kDa levels.
      Our data suggest that an alternative splicing event (OPN-c) promotes
      extracellular cleavage of OPN by MMP-9, thus releasing a distinct region of OPN
      (OPN-5 kDa) that is essential for HCC cellular invasion and appears to correlate
      with metastatic potential. The findings of this study may help to improve
      advanced-stage HCC prognosis and suggest the utility of small peptides for novel
      therapies.

PMID- 17452980
TI  - hAda3 regulates p14ARF-induced p53 acetylation and senescence.
AB  - Acetylation is thought to be a key event for p53 activation. We demonstrate that
      p14ARF-induced senescence of human mammary epithelial cells (MEC) is associated
      with p53 acetylation and requires hAda3, a component of histone acetyltransferase
      complexes and a p53 transcriptional coactivator. Expression of the N-terminal
      domain of hAda3 that binds p53 but not p300 blocked p14ARF-induced p53
      acetylation and protected MECs from senescence. Consistent with these findings,
      the human papillomavirus 16 E6 mutant Y54D, which selectively targets hAda3 but
      not p53 for degradation and protects MECs from p14ARF-induced senescence,
      inhibited p53 acetylation. In H1299 cells, hAda3 overexpression increased p300
      mediated p53 acetylation, which conversely decreased following small interfering
      RNA (siRNA) knockdown of hAda3. Moreover, depletion of hAda3 by siRNA inhibited
      endogenous p53 acetylation and accumulation of p21cip1 in response to ectopic
      p14ARF. These studies reveal that, in addition to its known ability to inhibit
      Mdm2-mediated p53 degradation, p14ARF signals through hAda3 to stimulate p53
      acetylation and the induction of cell senescence.

PMID- 17452981
TI  - Hypermethylation of the nel-like 1 gene is a common and early event and is
      associated with poor prognosis in early-stage esophageal adenocarcinoma.
AB  - The nel-like1 (NELL1) gene maps to chromosome 11p15, which frequently undergoes
      loss of heterozygosity in esophageal adenocarcinoma (EAC). NELL1 promoter
      hypermethylation was examined by real-time methylation-specific polymerase chain
      reaction in 259 human esophageal tissues. Hypermethylation of this promoter
      showed highly discriminative receiver-operator characteristic curve profiles,
      clearly distinguishing esophageal squamous cell carcinoma (ESCC) and EAC from
      normal esophagus (NE) (P<0.001). NELL1 normalized methylation values were
      significantly higher in Barrett's metaplasia (BE), dysplastic Barrett's (D) and
      EAC than in NE (P<0.0000001). NELL1 hypermethylation frequency was zero in NE but
      increased early during neoplastic progression, to 41.7% in BE from patients with
      Barrett's alone, 52.5% in D and 47.8% in EAC. There was a significant correlation
      between NELL1 hypermethylation and BE segment length. Three (11.5%) of 26 ESCCs
      exhibited NELL1 hypermethylation. Survival correlated inversely with NELL1
      hypermethylation in patients with stages I-II (P=0.0264) but not in stages III-IV
      (P=0.68) EAC. Treatment of KYSE220 ESCC and BIC EAC cells with 5-aza-2'
      deoxycytidine reduced NELL1 methylation and increased NELL1 mRNA expression.
      NELL1 mRNA levels in EACs with an unmethylated NELL1 promoter were significantly
      higher than those in EACs with a methylated promoter (P=0.02). Promoter
      hypermethylation of NELL1 is a common, tissue-specific event in human EAC, occurs
      early during Barrett's-associated esophageal neoplastic progression, and is a
      potential biomarker of poor prognosis in early-stage EAC.

PMID- 17452982
TI  - Roles of BCCIP in chromosome stability and cytokinesis.
AB  - The BRCA2 gene is involved in recombinational DNA repair and cytokinesis. BRCA2
      defects are associated with chromosomal abnormalities, which is a hallmark of
      genomic instability that contributes to tumorigenesis. Here, we show that
      downregulation of a BRCA2 interacting protein (BCCIP) in HT1080 cells leads to
      chromosomal polyploidization, centrosome amplification and abnormal mitotic
      spindle formation. The BCCIP knockdown cells can enter mitosis and retain spindle
      checkpoint, but fail to complete cytokinesis. Our data suggest an essential role
      of BCCIP in the maintenance of genomic integrity.

PMID- 17452983
TI  - 53BP1 deficiency in intestinal enterocytes does not alter the immediate response
      to ionizing radiation, but leads to increased nuclear area consistent with
      polyploidy.
AB  - The p53-binding protein 53BP1 has been implicated in the DNA damage response and
      genomic instability. Previous reports have highlighted these roles in vivo in
      haematopoietic lineages. To investigate the importance of 53BP1 to the DNA damage
      response in epithelial cells in vivo, we have investigated the role of 53BP1 in
      mediating apoptosis and proliferation within the murine small intestine following
      gamma-irradiation. 53BP1 deficiency does not affect the immediate response to
      gamma-irradiation with normal levels of apoptosis, proliferation and p53 and p21
      accumulation. However, 48 h post-gamma-irradiation there was a significant
      accumulation of cells with much larger nuclei marked by p53 and p21 accumulation.
      These data reflect increases in polyploidy observed 53BP1-/- deficient
      fibroblasts following gamma-irradiation. At 72 h post-irradiation both the 4N and
      8N populations were significantly increased in 53BP1-/- MEFS. Taken together,
      these results show that following in vivo exposure to gamma-irradiation, 53BP1 is
      dispensable for signalling apoptosis and cell-cycle arrest in the intestinal
      epithelium. However, it is important for prevention of genomic instability within
      this epithelial cell population.

PMID- 17452984
TI  - Tumor progression in Apc(1638N) mice with Exo1 and Fen1 deficiencies.
AB  - Flap endonuclease 1 (Fen1) and exonuclease 1 (Exo1) have sequence homology and
      similar nuclease capabilities. Both function in multiple pathways of DNA
      metabolism, but appear to have distinct in vivo nucleic acid substrates, and
      therefore distinct metabolic roles. When combined with Apc(1638N), Fen1 promotes
      tumor progression. Because of functional similarity to Fen1, and because Exo1 is
      involved in DNA mismatch repair (MMR) by interaction with Msh2 and Mlh1, genes
      that cause hereditary nonpolyposis colorectal cancer (HNPCC), we investigated the
      possibility that Exo1 might also act as a modifier to Apc(1638N). We present
      evidence that mice with combined mutations in Apc(1638N) and Exo1 and Apc(1638N),
      Exo1 and Fen1 genes show moderate increased tumor incidence and multiplicity in
      comparison to Apc(1638N) siblings, implying a low penetrance role for Exo1 in
      early gastrointestinal (GI) tumorigenesis. Despite a decrease in median survival
      (10 months) in Apc(1638N) Exo1 mice, their tumors do not progress any more
      rapidly than those of Apc(1638N). Instead these animals die from infections that
      are the result of impaired immune response. Apc(1638N) Exo1 Fen1 mice survive
      longer (18 months), and therefore appear relatively immune competent. They die of
      invasive GI tumors that display microsatellite instability (MSI). Our results
      show that Exo1 has a modest tumor suppressor function.

PMID- 17452985
TI  - Loss of the retinoblastoma tumor suppressor: differential action on
      transcriptional programs related to cell cycle control and immune function.
AB  - Functional inactivation of the retinoblastoma tumor suppressor gene product (RB)
      is a common event in human cancers. Classically, RB functions to constrain
      cellular proliferation, and loss of RB is proposed to facilitate the hyperplastic
      proliferation associated with tumorigenesis. To understand the repertoire of
      regulatory processes governed by RB, two models of RB loss were utilized to
      perform microarray analysis. In murine embryonic fibroblasts harboring germline
      loss of RB, there was a striking deregulation of gene expression, wherein
      distinct biological pathways were altered. Specifically, genes involved in cell
      cycle control and classically associated with E2F-dependent gene regulation were
      upregulated via RB loss. In contrast, a program of gene expression associated
      with immune function and response to pathogens was significantly downregulated
      with the loss of RB. To determine the specific influence of RB loss during a
      defined period and without the possibility of developmental compensation as
      occurs in embryonic fibroblasts, a second system was employed wherein Rb was
      acutely knocked out in adult fibroblasts. This model confirmed the distinct
      regulation of cell cycle and immune modulatory genes through RB loss. Analyses of
      cis-elements supported the hypothesis that the majority of those genes
      upregulated with RB loss are regulated via the E2F family of transcription
      factors. In contrast, those genes whose expression was reduced with the loss of
      RB harbored different promoter elements. Consistent with these analyses, we found
      that disruption of E2F-binding function of RB was associated with the
      upregulation of gene expression. In contrast, cells harboring an RB mutant
      protein (RB-750F) that retains E2F-binding activity, but is specifically
      deficient in the association with LXCXE-containing proteins, failed to upregulate
      these same target genes. However, downregulation of genes involved in immune
      function was readily observed with disruption of the LXCXE-binding function of
      RB. Thus, these studies demonstrate that RB plays a significant role in both the
      positive and negative regulations of transcriptional programs and indicate that
      loss of RB has distinct biological effects related to both cell cycle control and
      immune function.

PMID- 17452986
TI  - The melanoma tumor antigen, melanotransferrin (p97): a 25-year hallmark--from
      iron metabolism to tumorigenesis.
AB  - Melanotransferrin (MTf) or melanoma tumor antigen p97 is a transferrin (Tf)
      homolog that is found predominantly bound to the cell membrane via a glycosyl
      phosphatidylinositol anchor. The molecule is a member of the Tf superfamily and
      binds iron through a single high-affinity iron(III)-binding site. Since its
      discovery on the plasma membrane of melanoma cells, the function of MTf has
      remained intriguing, particularly in relation to its role in cancer cell iron
      transport. In fact, considering the crucial role of iron in many metabolic
      pathways, e.g., DNA synthesis, it was important to understand the function of MTf
      in the transport of this vital nutrient. MTf has also been implicated in diverse
      physiological processes, such as plasminogen activation, angiogenesis and cell
      migration. However, recent studies using a knockout mouse and post
      transcriptional gene silencing have demonstrated that MTf is not involved in iron
      metabolism, but plays a vital role in melanoma cell proliferation and
      tumorigenesis. In this review, we discuss the possible biological functions of
      MTf, particularly in relation to cancer.

PMID- 17452987
TI  - Human adipocytes induce an ERK1/2 MAP kinases-mediated upregulation of
      steroidogenic acute regulatory protein (StAR) and an angiotensin II-sensitization
      in human adrenocortical cells.
AB  - OBJECTIVES: Hypertension is a major complication of overweight with frequently
      elevated aldosterone levels in obese patients. Our previous work suggests a
      direct stimulation of adrenal aldosterone secretion by adipocytes. Owing to
      aldosterone's important role in maintaining blood pressure homeostasis, its
      regulation in obesity is of major importance. One objective was to determine the
      signaling mechanisms involved in adipocyte-induced aldosterone secretion. In
      addition to a direct stimulation, a sensitization toward angiotensin II (AngII)
      might be involved. The second objective was to determine a possible adipokines
      induced sensitization of human adrenocortical cells to AngII. DESIGN: Human
      subcutaneous adipocytes and adrenocortical cells, and the adrenocortical cell
      line NCI-H295R were used. Adrenocortical cells were screened for signal
      transduction protein expression and phosphorylation. Subsequently, steroidogenic
      acute regulatory protein (StAR), cAMP response element-binding protein (CREB),
      cAMP and phosphorylated extracellular regulated kinase were analyzed by Western
      blot, enzyme-linked immunosorbent assay, quantitative PCR, reporter gene assay
      and confocal microscopy to investigate their role in adipocyte-mediated
      aldosterone secretion. RESULTS: AngII-mediated aldosterone secretion was largely
      increased by preincubating H295R cells with adipocyte secretory products. StAR
      mRNA and StAR protein were upregulated in a time-dependent way. This
      steroidogenic effect was independent of the cAMP-protein kinase A (PKA) pathway
      as cellular cAMP was unaltered and inhibition of PKA by H89 failed to reduce
      aldosterone secretion. However, CREB reporter gene activity was moderately
      elevated. Upregulation of StAR was accompanied by ERK1/2 MAP kinase activation
      and nuclear translocation of the kinases. Inhibition of MAP kinase by UO126
      abolished adipokine-stimulated aldosterone secretion from primary human
      adrenocortical and H295R cells, and inhibited StAR gene activity. Adipokines
      stimulated steroidogenesis also in primary human adrenocortical cells, supporting
      a role in human physiology and/or pathology. CONCLUSIONS: Adipokines induce
      aldosterone secretion from human adrenocortical cells and sensitization of the
      cells to stimulation by AngII, possibly mediated via ERK1/2-dependent
      upregulation of StAR activity. This stimulation of aldosterone secretion could be
      one link between overweight and inappropriately elevated aldosterone levels.

PMID- 17452988
TI  - What is the quality of reporting in weight loss intervention studies? A
      systematic review of randomized controlled trials.
AB  - BACKGROUND: Despite the large number of randomized controlled trials (RCTs)
      assessing weight loss interventions, no study has assessed the quality of
      reporting in these trials. PURPOSE: To assess the quality of reporting of RCTs of
      weight loss interventions and to identify predictors of reporting quality.
      METHODS: The RCTs assessed were derived from a published systematic review of
      trials investigating the efficacy of weight loss interventions. For our study,
      two reviewers independently rated the quality of reporting in these trials, based
      on the Consolidated Standards for Reporting of Trials (CONSORT) Statement. We
      describe the quality of reporting using number (percent) of studies satisfying
      each of the 44 CONSORT criteria. We use generalized estimating equations (GEE) to
      fit a multivariable regression model to determine factors that are associated
      with the overall quality reporting score. RESULTS: We assessed 63 RCTs, of which
      25 were dietary-lifestyle trials, 22 were pharmacological trials and 16 were
      behavior-cognitive, exercise-lifestyle, or surgical trials. Less than half (46%)
      of the trials defined the primary outcome of the study; about 10% provided the
      description of the method of allocation concealment. Multivariable GEE results
      showed that the sample size, type of intervention (non-pharmacologic trials
      having lower scores than pharmacologic trials), and publication time relative to
      the CONSORT Statement publication in 1996 (publications after 1996 having higher
      scores) were strong predictors of the quality reporting score. Reporting a
      statistically significant result on the primary outcome was not significantly
      associated with the quality score. CONCLUSION: While the overall quality in
      reporting seemed to have improved since the publication of the revised CONSORT
      Statement in 1996, the reporting of some key methodologic aspects, such as clear
      description of primary outcome and method of allocation concealment, still
      requires improvements. Factors that are significantly associated with the overall
      quality reporting score can be used as surrogates in the review of protocols to
      enhance the quality of the final reports.

PMID- 17452989
TI  - Body mass index, physical activity and erectile dysfunction: an U-shaped
      relationship from population-based study.
AB  - OBJECTIVE: To investigate the relationships between body mass index (BMI),
      physical activity and erectile dysfunction (ED). DESIGN AND SUBJECTS: A
      population representative cross-sectional analytic study of ED in Hong Kong, with
      two-stage stratified random sampling, and face-to-face interviews conducted by
      trained interviewers with structured questionnaires. Study subjects were 1506 men
      aged 26-70. RESULTS: Age (odds ratio (OR)=1.30; 95% confidence interval (CI) 1.20
      1.40), physical activity (OR=0.91 per 500 kcal/week; 95% CI 0.84-0.98), and
      general psychological distress (OR=1.03 per GHQ score; 95% CI 1.00-1.06) were
      independently associated with ED after multivariate adjustments. An U-shaped
      relationship between BMI and ED was observed only among men with no exercise
      (<once/week): BMI <18.5 (OR=2.99; 95% CI 1.01-8.86), 18.5-19.9 (OR=2.66; 95% CI
      1.04-6.79), 20.0-20.9 (OR=1.37; 95% CI 0.49-3.79), 22.0-22.9 (OR=1.36; 95% CI
      0.58-3.17), 23.0-24.9 (OR=1.66; 95% CI 0.70-3.93), > or =25.0 (OR=2.47; 95% CI
      1.08-5.67) using BMI 21.0-21.9 as reference, adjusted for age, GHQ and smoking
      status. Being physically active (> or =1000 kcal/week) only reduced the risk of
      ED (OR=0.40, 95% CI 0.16-0.95) in men who were obese, adjusted for age, GHQ,
      smoking status and BMI. CONCLUSIONS: BMI and physical activity independently and
      differentially affected ED risk. BMI had greatest influence with low physical
      activity, and physical activity exerted greatest influence when BMI was high.
      This is the first study to demonstrate an U-shaped relationship between BMI and
      ED risk, but only in men with no exercise, and to identify underweight as a risk
      factor for ED. This relationship has clinical implications for obese as well as
      underweight individuals.

PMID- 17452990
TI  - Increased expression of the macrophage markers and of 11beta-HSD-1 in
      subcutaneous adipose tissue, but not in cultured monocyte-derived macrophages, is
      associated with liver fat in human obesity.
AB  - OBJECTIVE: To determine whether increased expression of macrophage markers and of
      inflammatory markers in subcutaneous adipose tissue is associated with liver fat
      in human obesity. We also determined whether expression of TNF (gene encoding TNF
      alpha), HSD11B1 (gene encoding 11beta-HSD-1) and RETN (gene encoding resistin) in
      cultured monocyte-derived macrophages differs between obese/overweight and non
      obese subjects. DESIGN: Cross-sectional comparison of obese/overweight and non
      obese subjects with respect to adipose tissue gene expression, gene expression in
      monocyte-derived macrophages, liver fat content and in vivo insulin sensitivity.
      SUBJECTS: Adipose tissue gene expression, gene expression in monocyte-derived
      macrophages, liver fat content and in vivo insulin sensitivity: 10 healthy non
      obese (24.2+/-1.0 kg/m(2)) and 10 healthy obese/overweight (33.1+/-1.7 kg/m(2))
      women. Gene expression in monocyte-derived macrophages: seven healthy non-obese
      (22.1+/-0.7 kg/m(2)) and seven healthy obese/overweight (36.9+/-2.2 kg/m(2))
      women. MEASUREMENTS: Adipose tissue biopsies and blood samples for isolation of
      peripheral mononuclear cells were taken after an overnight fast. Liver fat
      content was measured using magnetic resonance proton spectroscopy. Whole body
      insulin sensitivity was measured using the hyperinsulinemic euglycemic clamp
      technique. Expression levels of TNF, HSD11B1, RETN and the macrophage markers
      CD68 and ITGAM were determined by real-time PCR. RESULTS: In adipose tissue,
      expression of HSD11B1, ITGAM and CD68 was significantly increased in the
      obese/overweight as compared to the non-obese group. Expression of all these
      genes was closely positively correlated with liver fat content and inversely
      correlated with whole body insulin sensitivity. The associations between
      expression of CD68, ITGAM and HSD11B1 and liver fat were independent of obesity.
      There were no differences in TNF, HSD11B1, RETN or CD68 gene expression basally
      or after stimulation with lipopolysaccharide in monocyte-derived macrophages
      between obese/overweight and non-obese subjects. CONCLUSION: Accumulation of fat
      in the liver is associated with increased adipose tissue inflammation independent
      of obesity.

PMID- 17452991
TI  - The gender insulin hypothesis: a response to Wilkin and Murphy (2006).

PMID- 17452992
TI  - Truncal fat in relation to total body fat: influences of age, sex, ethnicity and
      fatness.
AB  - OBJECTIVE: To investigate the influence of age, sex, ethnicity and total fatness
      on central obesity in four ethnic populations. DESIGN: Cross-sectional analysis
      of study subjects enrolled from 1993 to 2005. SUBJECTS: A multi-ethnic (Caucasian
      (CA), African-American (AA), Hispanic-American (HA) and Asian (As)) convenience
      sample of 604 men and 1192 women (aged 18-96 years, body mass index 15.93-45.80
      kg/m(2)). MEASUREMENTS: Total body fat (TBF) and truncal fat were measured by
      dual-energy X-ray absorptiometry. General linear regression models were used to
      test for independent associations with log(10)-transformed truncal fat. RESULTS:
      For all ethnicities, men had a lower percent body fat and more truncal fat than
      women. Log(10-)transformed truncal fat increased with TBF approximately as a
      square root function. At older ages, there was a greater amount of truncal fat in
      CA, HA and As men (approximately 0.20-0.25 kg/decade) with the effect more
      pronounced in AA men ( approximately 0.33 kg/decade). For women, the increment of
      truncal fat per decade was reduced in CA and AA women (approximately 0.07 kg)
      compared with As and HA women (approximately 0.33 kg). Adjusted for mean values
      of covariates in our sample, AA had less truncal fat than As. CONCLUSION: The
      accumulation of truncal fat is strongly related to age, ethnicity and total
      fatness in both men and women.

PMID- 17452993
TI  - A longitudinal study of infant feeding and obesity throughout life course.
AB  - BACKGROUND: The Centers for Disease Control and Prevention and the US Department
      of Health and Human Services promote breastfeeding as a strategy for reducing
      childhood overweight. We evaluated the relation between infant feeding and the
      development of overweight and obesity throughout life course. METHODS: We
      investigated the association between infant feeding and obesity among 35,526
      participants in the Nurses' Health Study II who were followed prospectively from
      1989 to 2001. Mothers of participants provided information by mailed
      questionnaires on the duration of breast- and bottle-feeding, as well as the type
      of milk or milk substitute in the bottle. Information on body shape at ages 5 and
      10, weight at age 18, current weight between 1989 and 2001, and height was
      reported by the participants. RESULTS: The duration of breastfeeding, including
      exclusive breastfeeding, was not related to being overweight (25< or = body mass
      index (BMI) <30 kg/m(2)) or obese (BMI> or =30 kg/m(2)) during adult life. Women
      who were exclusively breastfed for more than 6 months had a risk of 0.94 (95%
      confidence interval (CI) 0.83-1.07) of becoming obese as adults compared with
      women who were not breastfed. Exclusive breastfeeding for more than 6 months was
      associated with leaner body shape at age 5 (odds ratio (OR)=0.81; 95% CI 0.65
      1.01 for the highest vs the lowest category of body shape) compared to women who
      were not breastfed or breastfed for less than 1 week, but this association did
      not persist during adolescence or adulthood. CONCLUSIONS: We did not find that
      having been breastfed was associated with women's likelihood of becoming
      overweight or obese throughout life course. Although breastfeeding promotes the
      health of mother and child, it is unlikely to play an important role in
      controlling the obesity epidemic.

PMID- 17452996
TI  - Fast food: unfriendly and unhealthy.
AB  - Although nutrition experts might be able to navigate the menus of fast-food
      restaurant chains, and based on the nutritional information, compose apparently
      'healthy' meals, there are still many reasons why frequent fast-food consumption
      at most chains is unhealthy and contributes to weight gain, obesity, type 2
      diabetes and coronary artery disease. Fast food generally has a high-energy
      density, which, together with large portion sizes, induces over consumption of
      calories. In addition, we have found it to be a myth that the typical fast-food
      meal is the same worldwide. Chemical analyses of 74 samples of fast-food menus
      consisting of French fries and fried chicken (nuggets/hot wings) bought in
      McDonalds and KFC outlets in 35 countries in 2005-2006 showed that the total fat
      content of the same menu varies from 41 to 65 g at McDonalds and from 42 to 74 g
      at KFC. In addition, fast food from major chains in most countries still contains
      unacceptably high levels of industrially produced trans-fatty acids (IP-TFA). IP
      TFA have powerful biological effects and may contribute to increased weight gain,
      abdominal obesity, type 2 diabetes and coronary artery disease. The food quality
      and portion size need to be improved before it is safe to eat frequently at most
      fast-food chains.

PMID- 17452994
TI  - Intermuscular adipose tissue rivals visceral adipose tissue in independent
      associations with cardiovascular risk.
AB  - BACKGROUND: The metabolic implications of intermuscular adipose tissue (IMAT) are
      poorly understood compared to those of visceral adipose tissue (VAT) even though
      the absolute quantities of both depots are similar in many individuals.
      OBJECTIVE: The aim was to determine the independent relationship between whole
      body IMAT and cardiovascular risk factor parameters. DESIGN: Whole body magnetic
      resonance imaging (MRI) was used to quantify total skeletal muscle (SM), total
      adipose tissue (TAT) of which IMAT, defined as the AT visible by MRI within the
      boundary of the muscle fascia, is a sub-component. Fasting serum measures (n=262)
      of glucose, total cholesterol (T-Chol), high-density lipoprotein cholesterol (HDL
      Chol), triglycerides (TG), protein bound glucose (PBG, n=206) and insulin (n=119)
      were acquired in healthy African-American (AA, n=78) and Caucasian (Ca, n=109)
      women (body mass index (BMI) 26.5+/-5.7 kg/m(2); 44.4+/-16.4 years) and men (39
      AA, 62 Ca; BMI 25.6+/-3.5 kg/m(2); 45.6+/-17.4 years). General linear models
      identified the independent effects of IMAT after covarying for SM, VAT, TAT,
      race, sex and two-way interactions. RESULTS: Significant independent associations
      were observed for IMAT with glucose (P<0.001), PBG (P<0.001) and T-Chol (P<0.05).
      The association of IMAT with cholesterol differed by race in such a manner that
      for a unit increase in IMAT, T-Chol increased more rapidly in Ca compared to AA
      (P<0.05). TG, HDL-Chol and insulin had no independent association with IMAT.
      CONCLUSION: The strong independent associations of IMAT with fasting glucose and
      PBG suggest that IMAT may be related to glucose metabolism; however, IMAT is also
      associated with T-Chol in Ca.

PMID- 17452997
TI  - Bcl-2 cleavages at two adjacent sites by different caspases promote cisplatin
      induced apoptosis.
AB  - The protein encoded by bcl-2 proto-oncogene plays an important role in the
      mitochondria-mediated apoptotic pathway. Although the general role of Bcl-2 is
      anti-apoptotic, previous work showed that Bcl-2 fragments cleaved by caspases
      could promote apoptotic process. We report herein that Bcl-2 protein was cleaved
      to produce two fragments of around 23 kDa in human hepatocarcinoma BEL-7404 cells
      or in Bcl-2 overexpressing CHO cells induced by cisplatin. Treating cells with
      the general caspase inhibitor z-VAD-fmk blocked the induced cleavage of Bcl-2.
      Mutagenesis analyses showed that Bcl-2 was cleaved by caspases at two adjacent
      recognition sites in the loop domain (YEWD(31) decrease AGD(34) decrease V),
      which could be inhibited by caspase-8 and -3 inhibitors, respectively.
      Overexpression of the carboxyl terminal 23 kDa fragments increased the
      sensitivity of CHO cells to cisplatin-induced apoptosis. These results indicate
      that Bcl-2 can be cleaved into two close fragments by different caspases during
      cisplatin-induced apoptosis, both of which contribute to the acceleration of
      apoptotic process.

PMID- 17452998
TI  - A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates
      inflammatory responses.
AB  - CD4+ helper T (TH) cells play crucial roles in immune responses. Recently a novel
      subset of TH cells, termed TH(IL-17), TH17 or inflammatory TH (THi), has been
      identified as critical mediators of tissue inflammation. These cells produce IL
      17 (also called IL-17A) and IL-17F, two most homologous cytokines sharing similar
      regulations. Here we report that when overexpressed in 293T cells, IL-17 and IL
      17F form not only homodimers but also heterodimers, which we name as IL-17A/F.
      Fully differentiated mouse THi cells also naturally secrete IL-17A/F as well as
      IL-17 and IL-17F homodimeric cytokines. Recombinant IL-17A/F protein exhibits
      intermediate levels of potency in inducing IL-6 and KC (CXCL1) as compared to
      homodimeric cytokines. IL-17A/F regulation of IL-6 and KC expression is dependent
      on IL-17RA and TRAF6. Thus, IL-17A/F cytokine represents another mechanism
      whereby T cells regulate inflammatory responses and may serve as a novel target
      for treating various immune-mediated diseases.

PMID- 17452999
TI  - The role of water channel proteins and nitric oxide signaling in rice seed
      germination.
AB  - Previous studies have demonstrated the possible role of several aquaporins in
      seed germination. But systematic investigation of the role of aquaporin family
      members in this process is lacking. Here, the developmental regulation of plasma
      membrane intrinsic protein (PIP) expression throughout germination and post
      germination processes in rice embryos was analyzed. The expression patterns of
      the PIPs suggest these aquaporins play different roles in seed germination and
      seedling growth. Partial silencing of the water channel genes, OsPIP1;1 and
      OsPIP1;3, reduced seed germination while over-expression of OsPIP1;3 promoted
      seed germination under water-stress conditions. Moreover, spatial expression
      analysis indicates that OsPIP1;3 is expressed predominantly in embryo during seed
      germination. Our data also revealed that the nitric oxide (NO) donors, sodium
      nitroprusside (SNP) and S-nitrosoglutathione (GSNO), promoted seed germination;
      furthermore, the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline
      1-oxyl-3-oxide, inhibited germination and reduced the stimulative effects of SNP
      and GSNO on rice germination. Exogenous NO stimulated the transcription of
      OsPIP1;1, OsPIP1;2, OsPIP1;3 and OsPIP2;8 in germinating seeds. These results
      suggest that water channels play an important role in seed germination, acting,
      at least partly, in response to the NO signaling pathway.

PMID- 17453000
TI  - Alteration of the serum levels of the epidermal growth factor receptor and its
      ligands in patients with non-small cell lung cancer and head and neck carcinoma.
AB  - Serum levels of the soluble epidermal growth factor receptor (sEGFR) and its
      ligands epidermal growth factor (EGF), transforming growth factor-alpha (TGF
      alpha) and amphiregulin (AR) were measured in healthy donors and patients with
      non-small cell lung cancer (NSCLC) and head and neck carcinoma (HNC). In NSCLC,
      we found sEGFR and EGF levels significantly lowered in patients with respect to
      healthy donors. In HNC patients, significantly diminished levels were found in
      the case of sEGFR, EGF and also AR. In both malignancies, no significant
      association was found between the serum levels of the molecules and the patients'
      gender, age or smoking habit. Only a significant association was found between
      the decrease of sEGFR and the absence of distant metastasis in NSCLC and the
      tumour stage in HNC. The most interesting result was that combining sEGFR and
      EGF, sensitivities of 88% in NSCLC and 100% in HNC were reached without losing
      specificity (97.8% in both cases). The use of discriminant analysis and logistic
      regression improved the sensitivity for NSCLC and the specificity for HNC. These
      data demonstrate a potentially interesting value of the serum levels of sEGFR and
      EGF, especially when combined, as markers for NSCLC and HNC.

PMID- 17453001
TI  - In silico mining identifies IGFBP3 as a novel target of methylation in prostate
      cancer.
AB  - Promoter hypermethylation is central in deregulating gene expression in cancer.
      Identification of novel methylation targets in specific cancers provides a basis
      for their use as biomarkers of disease occurrence and progression. We developed
      an in silico strategy to globally identify potential targets of promoter
      hypermethylation in prostate cancer by screening for 5' CpG islands in 631 genes
      that were reported as downregulated in prostate cancer. A virtual archive of 338
      potential targets of methylation was produced. One candidate, IGFBP3, was
      selected for investigation, along with glutathione-S-transferase pi (GSTP1), a
      well-known methylation target in prostate cancer. Methylation of IGFBP3 was
      detected by quantitative methylation-specific PCR in 49/79 primary prostate
      adenocarcinoma and 7/14 adjacent preinvasive high-grade prostatic intraepithelial
      neoplasia, but in only 5/37 benign prostatic hyperplasia (P < 0.0001) and in 0/39
      histologically normal adjacent prostate tissue, which implies that methylation of
      IGFBP3 may be involved in the early stages of prostate cancer development.
      Hypermethylation of IGFBP3 was only detected in samples that also demonstrated
      methylation of GSTP1 and was also correlated with Gleason score > or =7 (P=0.01),
      indicating that it has potential as a prognostic marker. In addition,
      pharmacological demethylation induced strong expression of IGFBP3 in LNCaP
      prostate cancer cells. Our concept of a methylation candidate gene bank was
      successful in identifying a novel target of frequent hypermethylation in early
      stage prostate cancer. Evaluation of further relevant genes could contribute
      towards a methylation signature of this disease.

PMID- 17453002
TI  - The role of versican isoforms V0/V1 in glioma migration mediated by transforming
      growth factor-beta2.
AB  - Versican is a large chondroitin sulphate proteoglycan produced by several tumour
      cell types, including high-grade glioma. The increased expression of certain
      versican isoforms in the extracellular matrix (ECM) plays a role in tumour cell
      growth, adhesion and migration. Transforming growth factor-beta2 (TGF-beta2) is
      an important modulator of glioma invasion, partially by remodeling the ECM.
      However, it is unknown whether it interacts with versican during malignant
      progression of glioma cells. Here, we analysed the effect of TGF-beta2 on the
      expression of versican isoforms. The expression of versican V0/V1 was upregulated
      by TGF-beta2 detected by quantitative polymerase chain reaction and
      immunoprecipitation, whereas V2 was not induced. Using time-lapse scratch and
      spheroid migration assays, we observed that the glioma migration rate is
      significantly increased by exogenous TGF-beta2 and inhibited by TGF-beta2
      specific antisense oligonucleotides. Interestingly, an antibody specific for the
      DPEAAE region of glycosaminoglycan-beta domain of versican was able to reverse
      the effect of TGF-beta2 on glioma migration in a dose-dependent manner. Taken
      together, we report here that TGF-beta2 triggers the malignant phenotype of high
      grade gliomas by induction of migration, and that this effect is, at least in
      part, mediated by versican V0/V1.

PMID- 17453003
TI  - Human papillomavirus in high- and low-risk areas of oesophageal squamous cell
      carcinoma in China.
AB  - To examine the potential roles of human papillomavirus (HPV) in oesophageal
      squamous cell carcinoma (ESCC) development, we examined the presence of HPV DNA
      in paraffin-embedded ESCC tissues collected from two areas with different ESCC
      incidence rates in China, that is, Gansu (n=26) and Shandong (n=33), using PCR
      with SPF10 primers, or PCR with GP5+/GP6+ primers combined with Southern blot
      hybridisation. HPV genotype was determined by the INNO-LiPA HPV genotyping kit.
      HPV DNA was detected in 17 cases (65%) in Gansu, where ESCC incidence is much
      higher than in Shandong, where HPV was positive in two samples (6%). HPV
      genotypes 16 and 18 were detected in 79 and 16% of HPV-positive samples,
      respectively. Real-time PCR analysis suggested the presence of integrated form of
      HPV DNA in all the HPV-16-positive samples, but its viral load was estimated to
      be only <1-2 copies cell(-1). We could not detect HPV 16/18 E6 protein expression
      by immunostaining in any of the HPV-16-positive samples. Neither p16(INK4a) nor
      p53 expression was related to HPV presence in ESCCs. Further studies seem
      warranted to examine the possible aetiological roles of HPV in ESCC.

PMID- 17453004
TI  - BRAF V600E mutation in anaplastic thyroid carcinomas and their accompanying
      differentiated carcinomas.
AB  - Frequency of a BRAF V600E mutation in anaplastic thyroid carcinoma, which is
      thought to be derived mainly from papillary carcinoma by multi-step
      carcinogenesis, is much lower than that in papillary carcinomas. To clarify this
      phenomenon, we analysed BRAF V600E mutation in 20 cases of anaplastic carcinoma
      and 13 accompanying differentiated carcinomas. Among twenty cases of anaplastic
      carcinomas, nine and four accompanied papillary and follicular carcinomas,
      respectively. BRAF V600E mutation was found in four (20%) cases. BRAF V600E
      mutation was found in three of nine (33.3%), none of four and one of seven
      (14.3%) anaplastic carcinomas with papillary carcinoma, follicular carcinoma and
      without differentiated components, respectively. All three papillary carcinomas
      accompanied by anaplastic carcinoma with a BRAF V600E mutation were also shown to
      have a BRAF V600E mutation. In summary, BRAF V600E mutation was occasionally
      observed in anaplastic carcinomas with papillary carcinoma, and the low frequency
      of BRAF V600E mutation in anaplastic carcinoma was thought to be due to the low
      frequency of anaplastic carcinomas with papillary carcinoma. These findings raise
      a question about the classical model of anaplastic transformation and suggest
      some roles of thyroid cancer stem cells in the generation of anaplastic
      carcinoma.

PMID- 17453005
TI  - Cancer, cardiovascular disease and diabetes mortality among women with a history
      of endometrial cancer.
AB  - Among 7182 women with endometrial cancer in Scotland, standardised mortality
      ratios (and 95% confidence intervals (CI)) were 6.38 (5.74-7.15) for all cancers
      and 1.10 (1.00-1.22) for circulatory diseases as underlying cause of death and
      2.81 (2.19-3.70) for diabetes as underlying/contributory cause of death.

PMID- 17453006
TI  - Number of siblings and the risk of solid tumours: a nation-wide study.
AB  - We analysed the effects of number of siblings on the risk of solid tumours using
      the Swedish Family-Cancer Database, including population-based information on
      over 11 million individuals and more than 178,000 cancer patients diagnosed
      between 1958 and 2004. Incidence rate ratios (RRs), estimated by Poisson
      regression models, were adjusted for age, sex, birth cohort, area of residence
      and socioeconomic status. Having eight or more siblings vs none increased the
      risk of stomach cancer (RR=1.83, 95% confidence interval (CI), 1.44-2.34). Anal
      cancer diagnosed before age 40 showed the strongest association with the total
      siblings (RR=3.27, 95% CI, 2.04-5.26 for five or more siblings vs none).
      Endometrial (RR=0.76, 95% CI, 0.70-0.82), testicular (RR=0.71, 95% CI, 0.62
      0.82), skin cancer (RR=0.82, 95% CI, 0.69-0.97) and melanoma (RR=0.72, 95% CI,
      0.65-0.79) showed strong decreased risks for five or more siblings vs none.
      Prostate cancer risk for those with five or more older siblings vs none was 1.38
      (95% CI, 1.23-1.55). Having five or more younger siblings was most strongly
      associated with stomach cancer (RR=1.59, 95% CI, 1.29-1.95) and melanoma
      (RR=0.68, 95% CI, 0.59-0.79). We conclude that sibship characteristics are strong
      correlates of cancer risk at several sites; plausible interpretations include
      socioeconomic status.

PMID- 17453007
TI  - Sensitivity of latex agglutination faecal occult blood test in the Florence
      District population-based colorectal cancer screening programme.
AB  - We evaluated the sensitivity for colorectal cancer (CRC) of the latex
      agglutination test (LAT), an immunochemical test routinely used in the Florence
      District screening programme since 2000. Sensitivity was calculated by the
      proportional interval cancer incidence method in a population of 27,503
      consecutive subjects screened in 2000-2002, interval cancers being identified by
      linkage to the Tuscany Cancer Registry files. Sensitivity was calculated overall
      and by gender, age, time since last negative LAT, CRC site, and rank of
      screening. Overall 1- and 2-year sensitivity estimates were 80.7 and 71.5%,
      respectively, suggesting that faecal occult blood testing screening sensitivity
      may be suboptimal due to testing or programme quality problems. Increasing
      screening sensitivity might be achieved if the detection rate of advanced
      adenomas could be increased without unacceptable loss in specificity.

PMID- 17453009
TI  - Patients with an unexplained microsatellite instable tumour have a low risk of
      familial cancer.
AB  - The cancer risk is unknown for those families in which a microsatellite instable
      tumour is neither explained by MLH1 promoter methylation nor by a germline
      mutation in a mismatch repair (MMR) gene. Such information is essential for
      genetic counselling. Families suspected of Lynch syndrome (n = 614) were analysed
      for microsatellite instability, MLH1 promoter methylation and/or germline
      mutations in MLH1, MSH2, MSH6, and PMS2. Characteristics of the 76 families with
      a germline mutation (24 MLH1, 2 PMS2, 32 MSH2, and 18 MSH6) were compared with
      those of 18 families with an unexplained microsatellite instable tumour. The mean
      age at diagnosis of the index patients in both groups was comparable at 44 years.
      Immunohistochemistry confirmed the loss of an MMR protein. Together this suggests
      germline inactivation of a known gene. The Amsterdam II criteria were fulfilled
      in 50/75 families (66%) that carried a germline mutation in an MMR gene and in
      only 2/18 families (11%) with an unexplained microsatellite instable tumour
      (P<0.0001). Current diagnostic strategies can detect almost all highly penetrant
      MMR gene mutations. Patients with an as yet unexplained microsatellite instable
      tumour likely carry a different type of mutation that confers a lower risk of
      cancer for relatives.

PMID- 17453010
TI  - A probabilistic view of immunology: drawing parallels with physics.
AB  - Regulating the strength and class of an immune response requires lymphocytes to
      act as complex signal integrating "machines", taking information from multiple
      sources while making decisions that affect the final outcome. Describing and
      understanding the decision-making behaviour of lymphocytes within the context of
      the dynamic multifaceted immune system appears immensely complicated. In this
      article I contrast two alternative frameworks, the deterministic and the
      probabilistic as competing paths to achieve successful quantitative immune
      models. As the two alternatives are traditional scientific rivals, I use the
      probabilistic fields in physics to highlight the potential value of the
      probabilistic perspective in immunology.

PMID- 17453008
TI  - Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published
      studies involving 12,155 patients.
AB  - The Ki-67 antigen is used to evaluate the proliferative activity of breast cancer
      (BC); however, Ki-67's role as a prognostic marker in BC is still undefined. In
      order to better define the prognostic value of Ki-67/MIB-1, we performed a meta
      analysis of studies that evaluated the impact of Ki-67/MIB-1 on disease-free
      survival (DFS) and/or on overall survival (OS) in early BC. Sixty-eight studies
      were identified and 46 studies including 12 155 patients were evaluable for our
      meta-analysis; 38 studies were evaluable for the aggregation of results for DFS,
      and 35 studies for OS. Patients were considered to present positive tumours for
      the expression of Ki-67/MIB-1 according to the cut-off points defined by the
      authors. Ki-67/MIB-1 positivity is associated with higher probability of relapse
      in all patients (HR=1.93 (95% confidence interval (CI): 1.74-2.14); P<0.001), in
      node-negative patients (HR=2.31 (95% CI: 1.83-2.92); P<0.001) and in node
      positive patients (HR=1.59 (95% CI: 1.35-1.87); P<0.001). Furthermore, Ki-67/MIB
      1 positivity is associated with worse survival in all patients (HR=1.95 (95% CI:
      1.70-2.24; P<0.001)), node-negative patients (HR=2.54 (95% CI: 1.65-3.91);
      P<0.001) and node-positive patients (HR=2.33 (95% CI: 1.83-2.95); P<0.001). Our
      meta-analysis suggests that Ki-67/MIB-1 positivity confers a higher risk of
      relapse and a worse survival in patients with early BC.

PMID- 17453011
TI  - Evaluation of an occupational therapy program for patients with spinal cord
      injury.
AB  - STUDY DESIGN: Clinical controlled trial. OBJECTIVES: To evaluate the
      effectiveness of an occupational therapy (OT) program combined with neuromotor
      rehabilitation, by assessing the degree of functional independence reached by
      patients with spinal cord injuries at first hospitalization. SETTINGS: Subjects
      selected from the Spinal Cord Unit of the Rehabilitation Institute of Montecatone
      (Imola, Italy). PARTICIPANTS: Thirty-six male patients below age 60, with
      complete paraplegia (ASIA-A) in thoracic-lumbar level, at first hospitalization.
      METHODS: Patients were divided into experimental and control groups. Subjects in
      the experimental group underwent neuromotor rehabilitation coupled with an OT
      program, whereas those in the control group followed neuromotor rehabilitation
      only. Increase in functional independence at discharge was evaluated by the
      Valutazione Funzionale Mielolesi (VFM) assessment scale. RESULTS: Patients in the
      experimental group showed a significant increase in the total VFM score, and in
      domains concerning transfers and wheelchair use. A significant improvement was
      observed in unmarried patients as compared to married ones. CONCLUSION: An OT
      service within a Spinal Cord Unit allows us to achieve a higher level of
      functional independence.

PMID- 17453012
TI  - Botulinum toxin for treatment of urinary incontinence due to detrusor
      overactivity: a systematic review of effectiveness and adverse effects.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To evaluate effectiveness and adverse
      effects of botulinum toxin (BTX) for treatment of urinary incontinence (UI) due
      to detrusor overactivity (DO). METHODS: Randomized controlled trials published in
      English before November 2006 were included if they enrolled subjects with UI
      caused by DO and reported incontinence outcomes. RESULTS: Three trials totaling
      104 subjects with DO refractory to antimuscarinic treatment were included. Two
      BTX-A trials enrolled primarily patients with NDO secondary to spinal cord injury
      (SCI) (93%). BTX-A decreased daily UI episodes compared to placebo but the
      reductions were only significantly different at a few of the time intervals
      during 24 weeks of follow-up. BTX-A was superior in reducing daily UI episodes in
      SCI subjects compared to intravesical resiniferatoxin at 12 and 18 months after
      injections. A small crossover study found BTX-B significantly more effective than
      placebo in reducing weekly UI episodes in subjects with predominately idiopathic
      DO. Adverse events (AEs) in BTX-A-treated subjects included urinary tract
      infection, pain at the injection site, hematuria and autonomic dysreflexia. Four
      subjects treated with BTX-B reported autonomic AEs. CONCLUSIONS: BTX may improve
      UI for subjects with refractory DO. The preferred dose and type of BTX is not
      known. Long-term efficacy and safety remain unclear and require conduct of larger
      RCT using standardized and validated clinical outcomes measures.

PMID- 17453014
TI  - Transcriptional regulation of vertebrate axon guidance and synapse formation.
AB  - The establishment of functional neural connections requires the growth of axons
      to specific target areas and the formation of synapses with appropriate synaptic
      partners. Several molecules that regulate axon guidance and synapse formation
      have been identified in the past decade, but it is unclear how a relatively
      limited number of factors can specify a large number of connections. Recent
      evidence indicates that transcription factors make a crucial contribution to the
      specification of connections in the nervous system by coordinating the response
      of neurons to guidance molecules and neurotransmitters.

PMID- 17453015
TI  - Drosophila olfactory memory: single genes to complex neural circuits.
AB  - A central goal of neuroscience is to understand how neural circuits encode memory
      and guide behaviour. Studying simple, genetically tractable organisms, such as
      Drosophila melanogaster, can illuminate principles of neural circuit organization
      and function. Early genetic dissection of D. melanogaster olfactory memory
      focused on individual genes and molecules. These molecular tags subsequently
      revealed key neural circuits for memory. Recent advances in genetic technology
      have allowed us to manipulate and observe activity in these circuits, and even
      individual neurons, in live animals. The studies have transformed D. melanogaster
      from a useful organism for gene discovery to an ideal model to understand neural
      circuit function in memory.

PMID- 17453016
TI  - Epigenetic regulation in psychiatric disorders.
AB  - Many neurological and most psychiatric disorders are not due to mutations in a
      single gene; rather, they involve molecular disturbances entailing multiple genes
      and signals that control their expression. Recent research has demonstrated that
      complex 'epigenetic' mechanisms, which regulate gene activity without altering
      the DNA code, have long-lasting effects within mature neurons. This review
      summarizes recent evidence for the existence of sustained epigenetic mechanisms
      of gene regulation in neurons that have been implicated in the regulation of
      complex behaviour, including abnormalities in several psychiatric disorders such
      as depression, drug addiction and schizophrenia.

PMID- 17453017
TI  - Cell cycle regulation in the postmitotic neuron: oxymoron or new biology?
AB  - Adult CNS neurons are typically described as permanently postmitotic but there is
      probably nothing permanent about the neuronal cell cycle arrest. Rather, it
      appears that these highly differentiated cells must constantly keep their cell
      cycle in check. Relaxation of this vigilance leads to the initiation of a cell
      cycle and entrance into an altered and vulnerable state, often leading to death.
      There is evidence that neurons which are at risk of neurodegeneration are also at
      risk of re-initiating a cell cycle process that involves the expression of cell
      cycle proteins and DNA replication. Failure of cell cycle regulation might be a
      root cause of several neurodegenerative disorders and a final common pathway for
      others.

PMID- 17453018
TI  - Binocular depth perception and the cerebral cortex.
AB  - Our ability to coordinate the use of our left and right eyes and to make use of
      subtle differences between the images received by each eye allows us to perceive
      stereoscopic depth, which is important for the visual perception of three
      dimensional space. Binocular neurons in the visual cortex combine signals from
      the left and right eyes. Probing the roles of binocular neurons in different
      perceptual tasks has advanced our understanding of the stages within the visual
      cortex that lead to binocular depth perception.

PMID- 17453028
TI  - Pharmacological approaches to the management of pain in the neonatal intensive
      care unit.
AB  - Effective and consistent management of neonatal pain remains a controversial
      issue. Premature infants are repeatedly subjected to painful tests and procedures
      or suffer painful conditions when they are most vulnerable. With different
      mechanisms transducing various types of pain the practice of 'one-drug fits all'
      becomes questionable. Clinicians must use the latest non-pharmacologic and
      pharmacologic therapies for effective management of neonatal pain, distress, or
      agitation. Pharmacologic strategies for dealing with neonatal pain in the
      neonatal intensive care unit are described. Opioid therapy, once considered the
      mainstay for neonatal analgesia, may not be as effective as previously thought.
      Morphine infusions do not alter the neurological outcomes of preterm neonates and
      may not be effective against acute pain. Alternative approaches with methadone,
      ketamine, or local anesthetics should be considered. Clinicians must understand
      the contextual circumstances underlying pain in individual neonates and tailor
      therapy accordingly, using the most current evidence related to neonatal pain
      assessment and management.

PMID- 17453037
TI  - Gestational diabetes mellitus: what is the optimal treatment modality?

PMID- 17453038
TI  - Earlier markers for cerebral palsy and clinical research in premature infants.
AB  - The diagnosis of cerebral palsy is based on evidence of impairment of the motor
      system, but symptoms become evident only as a premature infant matures. The
      diagnosis is made typically at 18 to 24 months of age, corrected for gestational
      age at birth. An earlier and more accurate way to identify infants destined to
      develop cerebral palsy may help improve the prognosis for this vulnerable
      population. For now, no antenatal, perinatal or postnatal test can predict
      cerebral palsy with a degree of certainty high enough to help providers or
      parents plan for an infant's future or make the best use of early intervention
      resources.

PMID- 17453039
TI  - Predicting proteinuria in hypertensive pregnancies with urinary protein
      creatinine or calcium-creatinine ratio.
AB  - OBJECTIVE: Evaluate the value of random urinary protein-creatinine (PrCr) and
      calcium-creatinine (CaCr) ratios to predict 24-h proteinuria in hypertensive
      pregnancies. STUDY DESIGN: Spot urine samples were collected before routine 24-h
      urine collections from consecutive pregnant women with hypertension (n=83).
      Reliability of spot urinary PrCr and CaCr to detect significant proteinuria
      (>or=300 mg/day) using 24-h urine protein as 'gold-standard' was assessed by
      receiver-operating characteristic (ROC) curve. RESULTS: Fifty-one patients
      (61.4%) had significant proteinuria (45 pre-eclampsia, 5 superimposed pre
      eclampsia, 1 renal hypertension). Area under ROC curve to predict proteinuria was
      0.82 (95% confidence interval (CI) 0.73 to 0.92, P<0.001) for PrCr and 0.55 (95%
      CI 0.43 to 0.68, P=0.2) for CaCr. A cutoff value of >0.19 for PrCr best predicted
      significant proteinuria with sensitivity, specificity, positive and negative
      predictive values and likelihood ratios (positive and negative), respectively, of
      80.4, 68.8, 80.4, 68.8%, 2.57 and 3.51. CONCLUSION: Spot urinary PrCr predicts
      total urinary protein excretion in hypertensive pregnancies.

PMID- 17453040
TI  - Global notes: instinctive resuscitation of a newborn by mother: a lesson to be
      learned.
AB  - The fact is that mother is the best combined pediatrician and neonatologist in
      the world. She is the most passionate and vested caregiver for the newborn,
      whether living and delivering in a modern hospital in a developed country or in a
      village in the remotest part of the globe; whether she is literate or illiterate.
      Let us focus our efforts on providing mothers the additional skills in caring for
      the baby in difficult situations immediately after birth.

PMID- 17453041
TI  - An unusual case of retinopathy of prematurity.
AB  - AIMS: Stage 3 retinopathy of prematurity (ROP) usually develops in the very small
      babies. An infant born at 30 (2) weeks' gestation and of birth weight 2102 g was
      found to have stage 3 ROP bilaterally. The unusual severity of the disease in a
      child of birth weight >2000 g prompted further investigation. The aim was to look
      for any genetic causes for ROP. METHODS: Chromosomal analysis followed by
      vasculoendothelial growth factor (VEGF) analysis. RESULTS: Unbalanced
      translocation 18p (monosomy) and 6p (trisomy). Overexpression of VEGF.
      CONCLUSIONS: Overexpression of VEGF contributed to the unusual severity of ROP in
      this relatively large baby.

PMID- 17453042
TI  - Pericardial effusion associated with an appropriately placed umbilical venous
      catheter.
AB  - Central venous catheterization is widely used in neonatal intensive care units to
      support tiny preterm babies. Pericardial effusion (PCE) and cardiac tamponade are
      uncommon but potentially fatal complications of percutaneous, umbilical and
      surgically placed central venous catheters related to intracardiac position or
      migration. This report describes a case of PCE arising from fluid infused via
      umbilical venous catheter. The case study highlights two important aspects: one,
      occurrence of PCE in a baby with satisfactory position of the umbilical catheter,
      and second, the life-saving application of basic echocardiography by bedside
      caregivers for the diagnosis and treatment of this critical condition.

PMID- 17453043
TI  - An unusual cause of neonatal coagulopathy and liver disease.
AB  - Congenital thyrotoxicosis is a rare and potentially fatal illness. We report a
      case in a preterm infant delivered to a mother known to have autoimmune endocrine
      disease. Diagnosis was difficult because the infant's presenting symptoms and
      signs closely resembled congenital viral infection with co-existent hepatic
      dysfunction and coagulopathy. The associated hepatic dysfunction was so severe
      that liver biopsy was scheduled before the diagnosis emerged. A high degree of
      clinical suspicion coupled with prenatal identification of pregnancies at risk of
      complication by congenital thyrotoxicosis is imperative to facilitate prompt
      diagnosis and treatment.

PMID- 17453044
TI  - Aicardi syndrome choroid plexus cysts.

PMID- 17453046
TI  - Assessment of neonatal anemia.

PMID- 17453047
TI  - Genome-wide transcriptional plasticity underlies cellular adaptation to novel
      challenge.
AB  - Cells adjust their transcriptional state to accommodate environmental and genetic
      perturbations. An open question is to what extent transcriptional response to
      perturbations has been specifically selected along evolution. To test the
      possibility that transcriptional reprogramming does not need to be 'pre-designed'
      to lead to an adaptive metabolic state on physiological timescales, we confronted
      yeast cells with a novel challenge they had not previously encountered. We
      rewired the genome by recruiting an essential gene, HIS3, from the histidine
      biosynthesis pathway to a foreign regulatory system, the GAL network responsible
      for galactose utilization. Switching medium to glucose in a chemostat caused
      repression of the essential gene and presented the cells with a severe challenge
      to which they adapted over approximately 10 generations. Using genome-wide
      expression arrays, we show here that a global transcriptional reprogramming
      (>1200 genes) underlies the adaptation. A large fraction of the responding genes
      is nonreproducible in repeated experiments. These results show that a nonspecific
      transcriptional response reflecting the natural plasticity of the regulatory
      network supports adaptation of cells to novel challenges.

PMID- 17453048
TI  - Chance and necessity in cellular response to challenge.

PMID- 17453049
TI  - Revealing static and dynamic modular architecture of the eukaryotic protein
      interaction network.
AB  - In an effort to understand the dynamic organization of the protein interaction
      network and its role in the regulation of cell behavior, positioning of proteins
      into specific network localities was studied with respect to their expression
      dynamics. First, we find that constitutively expressed and dynamically co
      regulated proteins cluster in distinct functionally specialized network
      neighborhoods to form static and dynamic functional modules, respectively. Then,
      we show that whereas dynamic modules are mainly responsible for condition
      dependent regulation of cell behavior, static modules provide robustness to the
      cell against genetic perturbations or protein expression noise, and therefore may
      act as buffers of evolutionary as well as population variations in cell behavior.
      Observations in this study refine the previously proposed model of dynamic
      modularity in the protein interaction network, and propose a link between the
      evolution of gene expression regulation and biological robustness.

PMID- 17453050
TI  - Silencing debate over autism.

PMID- 17453052
TI  - ALS: astrocytes move in as deadly neighbors.

PMID- 17453053
TI  - Something old, something new: BDNF-induced neuron survival requires TRPC channel
      function.

PMID- 17453054
TI  - The feeling of looking.

PMID- 17453055
TI  - Of sleep, memories and trauma.

PMID- 17453056
TI  - Serotonin guides the way.

PMID- 17453057
TI  - Paternal age and autism are associated in a family-based sample.

PMID- 17453058
TI  - Mapping regulatory variants for the serotonin transporter gene based on allelic
      expression imbalance.

PMID- 17453059
TI  - Rare plus common SERT variants in obsessive-compulsive disorder.

PMID- 17453060
TI  - Gene-environment correlations: a review of the evidence and implications for
      prevention of mental illness.
AB  - Family studies have demonstrated genetic influences on environmental exposure:
      the phenomenon of gene-environment correlation (rGE). A few molecular genetic
      studies have confirmed the results, but the identification of rGE in studies that
      measure genes and environments faces several challenges. Using examples from
      studies in psychology and psychiatry, we integrate the behavioral and molecular
      genetic literatures on rGE, describe challenges in identifying rGE and discuss
      the implications of molecular genetic findings of rGE for future research on gene
      environment interplay and for attempts to prevent disease by reducing
      environmental risk exposure. Genes affect environments indirectly, via behavior
      and personality characteristics. Associations between individual genetic variants
      and behaviors are typically small in magnitude, and downstream effects on
      environmental risk are further attenuated by behavioral mediation. Genotype
      environment associations are most likely to be detected when the environment is
      behaviorally modifiable and highly specified and a plausible mechanism links gene
      and behavior. rGEs play an important causal role in psychiatric illness. Although
      research efforts should concentrate on elucidating the genetic underpinnings of
      behavior rather than the environment itself, the identification of rGE may
      suggest targets for environmental intervention even in highly heritable disease.
      Prevention efforts must address the possibility of confounding between rGE and
      gene-environment interaction (G x E).

PMID- 17453061
TI  - Association of the DRD2 gene Taq1A polymorphism and alcoholism: a meta-analysis
      of case-control studies and evidence of publication bias.
AB  - We investigated the association of the dopamine D2 receptor (DRD2) Taq1A
      polymorphism and alcoholism, using meta-analytic techniques, and specifically
      undertook an investigation of possible publication bias. Potential publication
      bias represents a genuine risk to the integrity of published research, but its
      impact has rarely been documented. We observed a small effect of the DRD2 Taq1A
      polymorphism on risk of alcoholism, indicating increased alcoholism in
      individuals possessing the A1 allele of the Taq1A polymorphism (OR=1.21, 95% CI
      1.13-1.30, P<0.001). This association remained significant when data from samples
      of European and East Asian ancestry were analyzed separately. We did not find
      evidence for association in high-severity alcoholism compared to low-severity
      alcoholism. Removing the first published study significantly reduced the
      magnitude of the pooled effect size estimate, although the association remained
      significant. In addition, we observed evidence for possible publication bias and
      for the strength of individual study effect size to be inversely related to year
      of publication. These results support the association of the DRD2 Taq1A
      polymorphism with alcoholism. This conclusion is qualified by the possibility of
      publication bias in the literature and the observed between-study heterogeneity,
      which indicates that the observed association may differ in strength between
      populations or may not exist at all in some populations.

PMID- 17453062
TI  - Convergent genetic modulation of the endocrine stress response involves
      polymorphic variations of 5-HTT, COMT and MAOA.
AB  - Highly prevalent stress-related disorders such as major depression (MD) are
      characterised by a dysregulation of the neuroendocrine system. Although
      heritability for these disorders is high, the role of genes in the underlying
      pathophysiology is poorly understood. Here, we show that polymorphic variations
      in genes coding for serotonin transporter (5-HTT), catechol-O-methyl transferase
      (COMT) and monoamine oxidase A (MAOA) as well as sex differences influence the
      regulation of hypothalamic-pituitary-adrenal (HPA)-axis response to acute
      psychological and endocrine challenges. In our sample, the effects of COMT on the
      release of adrenocorticotrophin hormone (ACTH) depend on the presence of the low
      expression MAOA variant in the same individual. By including individuals varying
      in their degree of susceptibility to MD, we showed evidence of interactions
      between 5-HTT and MD susceptibility in baseline cortisol, and between MAOA and MD
      susceptibility in baseline ACTH measures, indicating a role for these genotypes
      in stable-state endocrine regulation. Collectively, these results indicate that
      the simultaneous investigation of multiple monoaminergic genes in interaction
      with gender have to be measured to understand the endocrine regulation of stress.
      These findings point towards a genetic susceptibility to stress-related
      disorders.

PMID- 17453063
TI  - Tryptophan hydroxylase 2 (TPH2) haplotypes predict levels of TPH2 mRNA expression
      in human pons.
AB  - Tryptophan hydroxylase isoform 2 (TPH2) is expressed in serotonergic neurons in
      the raphe nuclei, where it catalyzes the rate-limiting step in the synthesis of
      the neurotransmitter serotonin. In search for functional polymorphisms within the
      TPH2 gene locus, we measured allele-specific expression of TPH2 mRNA in sections
      of human pons containing the dorsal and median raphe nuclei. Differences in
      allelic mRNA expression--referred to as allelic expression imbalance (AEI)--are a
      measure of cis-acting regulation of gene expression and mRNA processing. Two
      marker SNPs, located in exons 7 and 9 of TPH2 (rs7305115 and rs4290270,
      respectively), served for quantitative allelic mRNA measurements in pons RNA
      samples from 27 individuals heterozygous for one or both SNPs. Significant AEI
      (ranging from 1.2- to 2.5-fold) was detected in 19 out of the 27 samples,
      implying the presence of cis-acting polymorphisms that differentially affect TPH2
      mRNA levels in pons. For individuals heterozygous for both marker SNPs, the
      results correlated well (r=0.93), validating the AEI analysis. AEI is tightly
      associated with the exon 7 marker SNP, in 17 of 18 subjects. Remarkably,
      expression from the minor allele exceeded that of the major allele in each case,
      possibly representing a gain-of-function. Genotyping of 20 additional TPH2 SNPs
      identified a haplotype block of five tightly linked SNPs for which heterozygosity
      is highly correlated with AEI and overall expression of TPH2 mRNA. These results
      reveal the presence of a functional cis-acting polymorphism, with high frequency
      in normal human subjects, resulting in increased TPH2 expression levels. The SNPs
      that correlate with AEI are closely linked to TPH2 SNPs previously shown to
      associate with major depression and suicide.

PMID- 17453064
TI  - The face of fear: Effects of eye gaze and emotion on visual attention.
AB  - We investigated whether a fearful expression enhances the effect of another's
      gaze in directing the attention of an observer. Participants viewed photographs
      of faces whose gaze was directed ahead, to the left or to the right. Target
      letters then appeared unpredictably to the left or right. As expected, targets in
      the location indicated by gaze were detected more rapidly. In nonanxious
      volunteers the effects of fearful gaze did not differ from neutral gaze, but
      fearful expression had a more powerful influence in a selected high anxious
      group. Attention is thus more likely to be guided by the direction of fearful
      than neutral gaze, but only in anxiety-prone individuals.

PMID- 17453065
TI  - [Profesor Doctor Antonio Del Solar Valenzuela].

PMID- 17453066
TI  - [Evaluation of a multiplex PCR assay to differentiate mycobacteria of the
      Mycobacterium tuberculosis complex in a reference laboratory].
AB  - Mycobacteria that cause tuberculosis in animals and humans belong to the
      Mycobacterium tuberculosis complex. Techniques for conventional diagnosis are
      time-consuming and do not differentiate between different strains belonging to
      the M. tuberculosis complex. The aim of this study was to evaluate a multiplex
      PCR assay applicable to mycobacteria in culture with the capacity to
      differentiate different strains belonging to the M. tuberculosis complex in a
      reference laboratory. Primers based on genomics regions of difference (RD)
      consisting in DNA segments that are present in M. tuberculosis, but
      differentially deleted in several members of M. tuberculosis complex were used in
      a PCR assay. The test was applied to 86 clinical isolates of mycobacteria. The
      pattern of amplification allowed differentiating between M. tuberculosis, M.
      bovis and M. bovis BCG in a single PCR reaction. This PCR multiplex assay may be
      used in a Reference Laboratory of Tuberculosis Diagnosis as a complementary test
      to differentiate mycobacteria strains belonging to the M. tuberculosis complex.
      This test significantly reduces the time period between culture and strain
      identification, and thus for could favor the adoption of better strain specific
      antimycobacterial regimens as well as identification of zoonotic transmission of
      M. bovis to humans.

PMID- 17453067
TI  - [Erroneous prescriptions of aciclovir and valaciclovir in herpes zoster
      treatment].
AB  - Medical prescription errors are frequent in community settings and information
      exploring its magnitude during antiviral treatment of herpes zoster is scarce. A
      questionnaire was applied to 31 physicians working in hospital- or community
      based settings in Santiago, Chile in order to characterize their dosing and
      timing preferences for aciclovir or valaciclovir prescriptions. Aciclovir was
      more often prescribed than valaciclovir (71.9 and 28.1%, respectively), but less
      than a third of prescription (27.3%) fulfilled the minimal aciclovir dosing and
      timing criteria for clinical efficacy (4 gr per day and <72 hours since rash
      initiation). The limited size of the simple prevented exploring factors linked to
      a misleading prescription. Appropriate knowledge on dosing and timing of
      aciclovir/valaciclovir therapy for herpes zoster was infrequent in a sample of
      physicians working in various clinical settings in Chile.

PMID- 17453068
TI  - [Neonatal sepsis in the era of antenatal antibiotic prophylaxis].
AB  - The aim of this study was to compare incidence, bacteriology and associated
      mortality of neonatal sepsis in a neonatal unit, after (2001-2004) and before
      (1995-1996) implementation of universal screening for prevention of Group B
      Streptococcus diseases. Early onset sepsis incidence decreased from 2.5 to 1 per
      1000 live births (p=0.03), with a decrease in the proportion of Group B
      Streptococcus cases from a 54% to 11% (p<0.01). In late onset sepsis, coagulase
      negative Staphylococci continued to be the predominant pathogen (49% of cases),
      and Candida albicans emerged as the second etiologic agent in the postscreening
      period. Sepsis associated mortality was low in both periods (2.2%).

PMID- 17453070
TI  - [Cost and outcome of hip's arthroplasty nosocomial infection. Case and control
      study].
AB  - Case-control study for evaluation of cost and outcome of nosocomial surgical site
      infection in primary hip arthroplasty during a period of 5 years. Mean
      hospitalization time in the orthopedic service was 54 days for cases, and 13 days
      for control (p<0.05). Mean hospitalization time in Intensive Care Unit (ICU) was
      1.1 days for cases. There were 0.83 post primary surgery interventions in cases,
      and a mean of 2.08 bacteriological cultures in each case. Controls didn't have
      hospitalizations in the ICU surgical reinterventions nor cultures necessary. The
      mean cost of infected patients was US $: 6,174.8. Mean cost in controls was US $:
      2,354.7. The excess of cost due to infections was US $: 2,354.7 on the average.
      Outcomes in cases were: normal function 30.8%; moderate or serious sequelae
      46.2%; death rate 15, 4%. The measured parameters contributed to raise case
      costs, and they caused an unsatisfactory outcome for two third of the patients.

PMID- 17453069
TI  - [Lymphomas and HIV infection in a reference hospital of Santiago, Chile: 1990
      2002: report of 14 cases and review].
AB  - The association of HIV infection and lymphoma in patients attending at the South
      Health Metropolitan Reference Centre is presented. OBJECTIVE: To analyse its
      incidence, clinical and pathologic manifestations, treatment and outcome. PERIOD
      OF STUDY: January 1990 to December 2002. RESULTS: 14 cases were detected, 10 non
      Hodgkin lymphoma patients (7 with high malignancy and 50% in stages III-IVB) and
      4 with Hodgkin lymphoma (3 with mixed cellularity, 2 in stage IVB). The annual
      incidence was 0.68%. Ten patients were classified under stage C3 of AIDS CDC
      criteria, the mean CD4 count was 139 cells/mm3 and mean CV was 5,32 log. Eighty
      six percent of patients presented with unique or multiples lymphonodes, with
      predominance of advanced lymphoma stage. Conventional CHOP chemotherapy was the
      treatment for high risk and extended non Hodgkin lymphomas and for extended
      Hodgkin lymphomas the ABVD protocol was administered. Six patients received
      antiretroviral therapy, 4 simultaneously with chemotherapy. Global mortality in
      this series was 71%, attributable to tumor disease per se or to sepsis. Four
      patients survived (18 to 50 months) in complete remission, 2 non Hodgkin
      lymphomas and 2 Hodgkin lymphomas. The low incidence of lymphoma and AIDS
      association and the high frequency of lymphomas with localized or generalized
      lymphonodes in this series are remarkable.

PMID- 17453071
TI  - [Etiology of ventilator-associated pneumonia in a university hospital.
      Association with comorbidity, previous use of antibiotics and mortality].
AB  - Ventilator-associated pneumonia (VAP) is a complication with an increased risk of
      morbidity and mortality. Inadequate antibiotic treatment is a risk factor of
      mortality which can be improved. For this reason it is important to know the
      local etiology of VAP. During a one year-period we investigated the etiology of
      VAP in a teaching hospital. Forty eight VAP were included, of which 19 were
      women. The median age was 59.5 (range 17-91 years), twelve VAP were early onset.
      Methicillin resistant Staphylococcus aureus (MRSA) was the main microorganism
      isolated, regardless of timing of diagnosis of VAP, followed by polimicrobial
      etiology, Acinetobacter sp and P. aeruginosa. Etiology was not associated with
      comorbidity; however previous antibiotic use was related with MRSA and
      polymicrobial etiology. Mortality was 35% and was mainly associated with P.
      aeruginosa isolation. CONCLUSION: MRSA was the main cause of VAP regardless of
      the timing of its occurrence.

PMID- 17453072
TI  - [Extended spectrum beta lactamases (ESBL) production in Acinetobacter baumannii
      strains isolated from Chilean hospitals belonging to VIII Region].
AB  - The resistance of Acinetobacter baumannii to ss-lactam antibiotics is mainly due
      to the synthesis of ss-lactamases. From a clinical point of view, this bacteria
      and others, grouped under the acronym SPACE (S: Serratia, P: Pseudomonas, A:
      Acinetobacter, C: Citrobacter, E: Enterobacter) are essentially Amp-C ss
      lactamases producers. There is no local information about ESBL presence in
      Acinetobacter. We studied ESBL production using the Ho and col. technique
      modified by adding cloxacillin as chromosomal ss-lactamases inhibitor. From 69
      isolates, with resistance to at least one third generation cephalosporin, only 7
      showed positive synergy test. Four of these amplified for TEM family gene, and
      one of these amplified also for the OXA family. Our study found a low ESBL
      production percentage, which agrees with the premise of Amp-C as the main
      mechanism of resistance to ss-lactam antibiotics in A. baumannii. However, the
      ESBL description in these bacteria emphasizes the capacity of expressing multiple
      resistance mechanisms.

PMID- 17453073
TI  - [Exfoliative erythroderma and infective dermatitis in an infant infected with
      human T-lymphotropic virus type I (HTLV I)].
AB  - We report a HTLV-I positive infant, whose infection was confirmed by polymerase
      chain reaction. The infant presented with an acute, severe, generalized eczema,
      exfoliation and severe erythroderma that yielded to an acute proteic malnutrition
      and frequent staphylococcal infections, unresponsive to treatment, since the
      second month of life. Immunodeficiencies from other origin and other causes of
      erythroderma were ruled out. The histopathology studies and clinical course
      yielded to the diagnosis of infective dermatitis associated to HTLV-I. A review
      of the literature is performed.

PMID- 17453074
TI  - [Mediastinal hydatid cyst. Case report and review].
AB  - Hydatid disease is caused by the larval stages of a cestodes belonging to the
      genus Echinococcus. In humans, hydatid larva and cysts are located >90% in the
      liver and/or lungs. Primary mediastinal location, with absence of documented lung
      infection, is extremely rare and has not been previously reported in Chile. We
      report the first case of a primary mediastinal hydatid cyst in Chile and review
      the literature. A 38 year old woman was admitted because of a painful right
      supraclavicular mass, dyspnea on exertion and logical dysphagia. Presurgical
      evaluation evidenced a mediastinal tumor extending to the cervical region that
      was successfully removed. The diagnosis of mediastinal hydatid cyst was confirmed
      macroscopically and by biopsy.

PMID- 17453075
TI  - [Diagnosis and treatment of the hydatidosis].

PMID- 17453076
TI  - [Bacillary angiomatosis caused by Bartonella quintana in an human
      immunodeficiency virus positive patient].
AB  - We report the first case of bacillary angiomatosis due to Bartonella quintana
      affecting a Chilean a HIV positive patient in Chile. He was a 27 years old,
      heterosexual male, indigent man known to be HIV positive serological status known
      from September, 2003, under irregular medical control. On April, 2005, he
      presented a progressive abscess in the frontal region and erythematous papules in
      the extremities, that extended to face, thorax and mucoses, becoming nodular and
      violaceous lesions. Bacillary angiomatosis diagnosis was initially sustained on
      account of the clinical manifestations, and was confirmed by serology and Warthin
      Starry staining from a skin biopsy. The etiological agent was identified as
      Bartonella quintana through universal RPC performed from a cutaneous nodule to
      detect 16S rRNA gen. Azithromycin plus ciprofloxacin was started, besides of anti
      retroviral therapy antiretroviral, with the lesions being progressively
      disappearing.

PMID- 17453077
TI  - [Foot and mouth disease in human beings. A human case in Chile].
AB  - Foot and mouth disease (FMD) of cattle can cause a significant economic burden
      and is thus for one of the most feared of cattle disease. FMD is endemic in South
      America, Africa, Asia and parts of Europe and it is characterized by vesicles in
      different locations, mainly mouth, feet and teats leading to severe animal
      weakness. Currently most countries refuse to import livestock and livestock
      products from FMD areas. North and Central America are currently free of FMD and
      Chile is free of FMD from 1987. Approximately 40 cases of human infection with
      FMD virus have been reported, mostly in Europe, and confirmed by virus isolation
      and the detection of a specific immune response. We discuss the case of a human
      infection with FMD virus occurred in Chile in 1961 and other relevant cases
      reported. FMD does not currently present a threat to public health. Even though
      the FMD virus has the potential to mutate rapidly and emerge as a significant
      human zoonosis; the rarity of the disease in humans despite a long history of
      close contact with FMD infected animals suggests that the risk is highly
      improbable. Then FMD should not be managed as a zoonosis.

PMID- 17453079
TI  - [About infection agents, zoophytes, animalcules and infusories].
AB  - By definition, zoophytes are organisms with characteristics which are
      intermediate between plants and animals. The concept is already outlined by
      Aristotle in his Historia Animalium. In the XVIII century, the great Swedish
      naturalist Carolus Linnaeus, in the tenth edition of his Systema Naturae,
      included the order Zoophyta within the class of Vermes. In this classification,
      for the first time the curious animalcules (infusories), discovered by van
      Leeuwenhoek in the late XVII century, were formally classified as zoophytes and
      were incorporated specifically into the genus Chaos. Audaciously, Linnaeus also
      conjectured that the infectious agents could be related to the animalcules
      infusories, though he left the corresponding demonstration to posterity.

PMID- 17453080
TI  - Effect of lycopene from cooked tomatoes on serum antioxidant enzymes, lipid
      peroxidation rate and lipid profile in coronary heart disease.
AB  - INTRODUCTION: This present study aims to evaluate the beneficial effect of
      tomatoes, a rich source of lycopene, which is a relatively new carotenoid known
      to play an important role in human health and disease. METHODS: We investigated
      the lipid peroxidation rate by estimating malondialdehyde (MDA), levels of serum
      enzymes involved in antioxidant activities such as superoxide dismutase,
      glutathione peroxidase, glutathione reductase, reduced glutathione and lipid
      profile, which includes total cholesterol, triglycerides, high density
      lipoprotein, low density lipoprotein and very low density lipoprotein in a
      coronary heart disease (CHD) group and an age-matched control group. RESULTS: We
      observed significantly lower levels of serum antioxidant enzymes and very high
      lipid peroxidation rate in the CHD group, when compared to the controls (p-value
      is less than 0.001). At the same time, we observed significantly higher levels of
      lipids in the CHD group, when compared to the controls (p-value is less than
      0.001). 60 days of tomato supplementation in the CHD group showed a significant
      improvement in the levels of serum enzymes involved in antioxidant activities and
      decreased lipid peroxidation rate (p-value is less than 0.001), but there were no
      significant changes in lipid profile (p-value is greater than 0.10). CONCLUSION:
      These findings suggest that tomato lycopene may have considerable therapeutic
      potential as an antioxidant but may not be used as a hypolipidaemic agent in CHD.

PMID- 17453081
TI  - Intracardiac blood-filled cysts of the heart: a rare cause of embolic stroke.
AB  - Intracardiac blood cysts are thin-walled congenital cysts located in the
      endocardium and are seen predominantly in infants. They are rare in adults and
      are typically asymptomatic. However, complications such as valve dysfunction and
      left ventricular outflow tract obstruction have been reported in adults. We
      report a 42-year-old woman who developed an embolic stroke in association with
      intracardiac blood cysts. To the best of our knowledge, this is the first case
      report of intracardiac blood cysts manifesting as an embolic stroke.

PMID- 17453082
TI  - Low velocity traumatic dissection of the internal carotid artery presenting as a
      stroke after a slash injury.
AB  - Low velocity traumatic dissection of the carotid artery is an infrequent but
      serious complication of blunt cranio-cervical injury. A 25-year-old man was hit
      by a blunt sickle over his chest and left side of his neck, and sustained open
      wounds over zone II of the neck. At that time, he had no neurological deficits
      and the wounds were sutured primarily. On the sixth day, while he was undergoing
      a change of dressing for the wounds, he suddenly became unconscious, and on
      recovery hours later, he was aphasic. Computed tomography showed a left posterior
      fronto-temporal ischaemic infarct in the territory of the middle cerebral artery.
      Colour Doppler ultrasonography showed an intimal tear and thrombus in the left
      common carotid artery. We discuss the possible mechanism of neurological deficits
      and also emphasise that in any patient with blunt injury to the neck, new
      neurological deficits should prompt us to suspect carotid artery injuries.

PMID- 17453083
TI  - Induction of atrioventricular nodal reentry tachycardia with intravenous
      adenosine.
AB  - Adenosine, used to terminate paroxysmal supraventricular tachycardia (SVT), is
      often useful in understanding the mechanism of tachycardia. This case report
      describes induction of SVT with adenosine in a 36-year-old man presenting with
      recurrent palpitations. After a short run of conduction via both slow and fast
      pathways, SVT was induced following a long PR interval. The long PR interval
      resulted by conduction via the slow pathway due to the preferential conduction
      block by adenosine over fast pathway. The notching at the terminal part of QRS
      during antegrade slow pathway conduction and during tachycardia indicated
      activation of the atrium via retrograde fast pathway. This electrocardiographical
      feature confirmed the mechanism of the tachycardia as atrioventricular nodal
      reentrant tachycardia.

PMID- 17453084
TI  - Ebstein's anomaly, Wolff-Parkinson-White syndrome and rheumatic mitral stenosis:
      role for combined electrophysiological and surgical management.
AB  - The coexistence of rheumatic mitral stenosis, Ebstein's anomaly and Wolff
      Parkinson-White syndrome is an uncommon entity. To our knowledge, the successful
      management of this combination of lesions has not been previously described. We
      report a 23-year-old woman with the combination of these abnormalities. She was
      managed with preoperative electrophysiological study, followed by mitral valve
      replacement and Danielson's repair of tricuspid valve. The management issues
      involved are discussed in detail.

PMID- 17453085
TI  - Congenital diaphragmatic eventration in an adult: a diagnostic dilemma.
AB  - Eventration of the diaphragm is a rare condition where the muscle is permanently
      elevated, but retains its continuity and attachments to the costal margins. It is
      seldom symptomatic and often requires no treatment, but may be confused with a
      traumatic rupture of the diaphragm. We present a 51-year-old man with previously
      undiagnosed congenital eventration, mimicking traumatic rupture of the diaphragm.
      The role of clinical examination, imaging and diagnostic laparoscopy to
      differentiate between eventration and traumatic rupture of the diaphragm are
      discussed.

PMID- 17453086
TI  - Dislocation after total knee arthroplasty.
AB  - Two cases of dislocation of total knee arthroplasty presented to us within the
      same week. The first patient is a 71-year-old woman who underwent bilateral
      primary total knee arthroplasty. The left knee dislocated three weeks after the
      surgery. Due to failure of conservative measures, she underwent revision total
      knee arthroplasty. The other patient is a 72-year-old woman presenting ten years
      after primary total knee arthroplasty, with a traumatic dislocation of the knee
      joint. She was treated as an outpatient with closed manipulative reduction.

PMID- 17453087
TI  - Extended double pedicle free tensor fascia latae myocutaneous flap for abdominal
      wall reconstruction.
AB  - Extensive full thickness anterior abdominal wall defects pose a difficult
      challenge to the reconstructive surgeon. The objectives of reconstruction are the
      support of the intra-abdominal structures in order to preserve the functional
      integrity and achieve an aesthetically-acceptable appearance. Autologous tissues
      are versatile and provide the best reconstructive option in this type of defects.
      The tensor fascia latae myocutaneous flap provides identical abdominal wall
      musculofascial cover for full thickness defects. In extensive defects, the
      extended tensor fascia latae flap is a versatile option with a second
      microvascular anastomosis at the distal end of the flap. A total anterior
      abdominal wall soft tissue tumour resection defect was reconstructed with the use
      of the double pedicle extended free tensor fascia latae myocutaneous flap in a 60
      year-old man. The patient however succumbed to the disease process six months
      post-reconstruction. During the follow-up period, there was no evidence of hernia
      at the anterior abdominal wall.

PMID- 17453088
TI  - Two cases of isochromosome 18q syndrome.
AB  - Patients with isochromosome 18q, a rare cytogenetic abnormality, also reported as
      Edwards syndrome, is the second most common autosomal trisomy. However, the
      phenotypic features and survival of these patients are not uniform and depend
      upon the portion of chromosomes getting duplicated or deleted. The survival of
      these children may be longer, hence a good cytogenetic diagnosis is a must.
      Morphological characteristics of isochromosome 18q are not yet fully delineated
      because of the rarity of the cases and as most cases are aborted medically or
      terminate spontaneously. We report two cases of isochromosome 18q, one male aged
      two years old and the other a male aged eight months old, and review the
      literature on this rare syndrome.

PMID- 17453089
TI  - Progressive pseudorheumatoid chondrodysplasia of childhood.
AB  - Progressive pseudorheumatoid chondrodysplasia is an autosomal recessively
      inherited skeletal dysplasia, characterised by platyspondyly and progressive
      arthropathy. We report a 26-year-old woman who presented with a history of
      waddling gait, progressive restriction of movements of several joints and
      swelling of interphalangeal joints since her late childhood. She was diagnosed to
      have progressive pseudorheumatoid chondrodysplasia associated with synovial
      osteochondromatosis.

PMID- 17453090
TI  - Intracranial metastases from carcinoma of the cervix.
AB  - Uterine cervix carcinoma usually spread by local extension and through the
      lymphatics to the retroperitoneal lymph nodes. Brain metastases are extremely
      rare in the course, are usually seen late and have poor prognosis. We report a 49
      year-old woman with squamous cell carcinoma of the cervix who developed right
      parieto-occipital lobe metastasis after three years of treatment of the primary
      disease. The presenting symptoms of the metastatic disease were hemiparesis,
      headache, and vomiting. Her hemiparesis improved after surgical excision of the
      metastasis. Treatment in these cases is mainly palliative but may offer
      symptomatic relief and improvement in the quality of life.

PMID- 17453091
TI  - Women's mental health: an overrated issue or unrecognised need?

PMID- 17453092
TI  - Of pruritus and terrorism...

PMID- 17453093
TI  - Jean-Martin Charcot (1825-1893): pathologist who shaped modern neurology.

PMID- 17453094
TI  - Gender differences in mental health.
AB  - Effective strategies for mental disorders prevention and its risk factors'
      reduction cannot be gender neutral, while the risks themselves are gender
      specific. This paper aims to discuss why gender matters in mental health, to
      explain the relationship of gender and health-seeking behaviour as a powerful
      determinant of gender differences, to examine the gender differences in common
      mental health disorders, namely, depressive and anxiety disorders, eating
      disorders, schizophrenia, and domestic violence, and finally, to raise some
      recommendations stemming from this review.

PMID- 17453095
TI  - Phenol and menthol in the treatment of chronic skin lesions following mustard gas
      exposure.
AB  - INTRODUCTION: Chronic skin lesions are common late complications of sulphur
      mustard exposure in veterans injured in chemical warfare. Pruritus is the most
      common complaint in the chronic phase, with significant effects on the patient's
      quality of life. The current study evaluated the efficacy of a combination of one
      percent phenol and one percent menthol in the control of pruritus in these
      affected patients. METHODS: This randomised, double-blinded clinical trial was
      performed in chemical warfare-injured veterans with mustard gas-induced pruritus.
      80 subjects were selected randomly and divided into two equal groups. One group
      was treated with a combination of one percent phenol and one percent menthol
      twice a day, while the other group received a placebo. The therapeutic effects
      and side effects were evaluated during a six-week treatment course. Pruritus
      score with a range of 1-48 points was used to calculate the severity of pruritus
      before and after treatment in both groups. RESULTS: The final pruritus score in
      the drug group was significantly different, compared with the placebo group (p
      value equals 0.03). There was also a statistically-significant difference between
      the pre-treatment (19 points) and post-treatment (15.5 points) pruritus scores in
      the drug group (p-value equals 0.001), but there was no significant difference in
      the response in the placebo group (p-value equals 0.66). Only a few patients had
      complaints about the drug, and these were generally minor. The most common
      complaints were of the greasy nature of the drug and its intolerable odour.
      CONCLUSION: A phenol one percent and menthol one percent combination has
      significant therapeutic effects for mustard gas-induced pruritus in chemical
      warfare-injured veterans, in comparison with the placebo.

PMID- 17453096
TI  - Leukoaraiosis as a predictor for mortality and morbidity after an acute ischaemic
      stroke.
AB  - INTRODUCTION: Leukoaraiosis (LA) is a term that defines an abnormal appearance of
      the subcortical white matter of the brain on neuroimaging. This study was done to
      evaluate the predictive value of LA in terms of mortality, disability and
      cognitive decline at three months post-stroke and also to identify the risk
      factors that are independently associated with LA in a stroke population.
      METHODS: This was a prospective observational study of all patients with acute
      ischaemic stroke who were admitted to Hospital Universiti Kebangsaan Malaysia
      from June to November 2004. A single observer using the pre-defined diagnostic
      criteria recorded the information on demography, Barthel Index and mini-mental
      state examination. LA was diagnosed on brain computed tomography alone. RESULTS:
      60 patients were recruited into the study. Three patients (five percent) died and
      LA was present in 29 patients (48 percent). There was no significant association
      between LA and mortality (p-value equals 0.89). The independent risk factors that
      were associated with LA were age (odds-ratio [OR] 4.43; 95 percent confidence
      interval [CI] 1.28-15.27) and hypertension (OR 14.3; 95 percent CI 1.40-147.42).
      There was a significant association between LA with early dementia (OR 3.53; 95
      percent CI 1.19-10.49). However, LA did not significantly predict any functional
      disability (Barthel Index is less than 60) in the study population (p-value
      equals 0.45). CONCLUSION: Development of LA correlates significantly with ageing
      and hypertension. The presence of LA can also predict early cognitive dysfunction
      but is not associated with functional disability at three months post-stroke.

PMID- 17453097
TI  - Determinants of length of stay during post-stroke rehabilitation in community
      hospitals.
AB  - INTRODUCTION: Length of stay (LOS) in hospitals is the largest contributor of
      direct stroke care cost. Rehabilitation accounts for 16 percent of healthcare
      cost in the six-month post-stroke period. It is important to determine factors
      extending LOS in rehabilitation hospitals to identify focus areas of cost-control
      strategies. The aim of the study was to ascertain the predictors of LOS of post
      stroke patients admitted into two community hospitals offering rehabilitation.
      METHODS: An observational cohort study was conducted on 200 stroke patients
      admitted from acute hospitals into two community hospitals. Data collected
      included baseline sociodemographical variables, and the National Institute of
      Health Stroke Scale, Abbreviated Mental Test, Geriatric Depression Scale and
      Barthel Index were used to assess neurological impairment, cognitive impairment,
      depressive symptoms and functional disability, respectively. Medical
      complications (defined as new or exacerbated medical problems that generated
      additional physician evaluation, a change in medication or additional medical
      intervention), after patients were admitted to the community hospitals until
      discharged, were recorded. The outcome variables measured were length and cost of
      stay. RESULTS: The mean LOS in our study was 34.4 (standard deviation [SD] 18.4)
      days, and the mean cost of hospital stay was S$2,410.83 (SD S$2,167.26). Length
      and cost of hospital stay were significantly correlated (r equals 0.52; p-value
      is less than 0.01). On multiple linear regression analysis, the significant
      variables positively associated with LOS were medical complications and
      functional dependence on admission. Significant variables negatively associated
      with LOS were unplanned discharge and recurrent strokes. CONCLUSION: Medical
      complication is a key reversible determinant of increased LOS of post-stroke
      patients receiving rehabilitation in community hospitals. Strategies for
      prevention, early detection and treatment of medical complications during stroke
      rehabilitation are discussed.

PMID- 17453098
TI  - Heart failure cohort in Singapore with defined criteria: clinical characteristics
      and prognosis in a multi-ethnic hospital-based cohort in Singapore.
AB  - INTRODUCTION: There are limited data on heart failure (HF) cohorts with objective
      clinical definition of HF. Many observational HF studies were based on discharge
      diagnosis codes, making them subjective. Many did not have contemporaneous left
      ventricular function assessment. This study was done to evaluate the
      characteristics and one-year prognosis of a single centre multi-ethnic Asian
      inpatient HF cohort, with these limitations addressed, with the aim of yielding a
      more accurate picture of true HF. METHODS: This was an observational prospective
      study. Patients who fulfilled the modified Framingham criteria for clinical HF
      and study inclusion criteria of serum creatinine level less than 267 micromol/L,
      serum albumin level greater than 28 g/L, and a contemporaneous trans-thoracic
      echocardiography (TTE) study were enrolled. TTE studies ordered were attempted
      within 72 hours. RESULTS: 173 patients were enrolled into the study. TTE was done
      within 72 hours of admission for 86.1 percent (n = 149) of the participants.
      Diastolic HF constituted 22.0 percent of the cohort. The mean age of the
      participants was 68.7 (standard deviation, 12.0) years. The prevalence of elderly
      patients, diabetes mellitus, hypertension and ischaemic cardiomyopathy were high.
      The one-year mortality rate was 20.8 percent (n = 36). The one-year death or
      readmission for any cause rate was 69.4 percent (n = 120). The mean time in
      hospital for any cause within the one year was 11.8 +/- 17.9 days. Ethnicity had
      prognostic implications. Being elderly, having elevated random blood glucose or
      serum creatinine levels were associated with a worse prognosis. CONCLUSION: With
      strict methodology, HF is truly a disease of the elderly, with significant one
      year mortality and morbidity consequences. Prognostic characteristics are
      reviewed.

PMID- 17453099
TI  - Exchange transfusion in neonatal hyperbilirubinaemia: experience in Isfahan,
      Iran.
AB  - INTRODUCTION: This study aims to determine the aetiology and complications of
      exchange transfusion (ET) performed for neonatal hyperbilirubinaemia in Isfahan,
      Iran. METHODS: A retrospective chart review of 68 term and near-term newborns who
      underwent ET at two perinatal centres in Isfahan, Iran between January 2001 and
      January 2004, was performed. RESULTS: Of the 68 patients who underwent ET, nine
      (13.2 percent) required more than one ET. The most common causes of ET overall
      were ABO incompatibility (22.1 percent) and glucose-6-phosphate dehydrogenase
      deficiency (19.1 percent). The maximum total serum bilirubin concentration was
      25.9 +/- 7.5 mg/dL. ET complications occurred in 14 neonates (20.9 percent), the
      most common being thrombocytopenia (6 percent). One (1.5 percent) of the 68
      patients died of complications, probably attributable to ET. CONCLUSION: ET
      causes high morbidity, even in term and near-term newborns. Therefore, it should
      be initiated only when the benefit of preventing kernicterus outweighs the
      complications associated with the procedure.

PMID- 17453100
TI  - Evaluation of neonatal indirect hyperbilirubinaemia at Zanjan Province of Iran in
      2001-2003: prevalence of glucose-6-phosphate dehydrogenase deficiency.
AB  - INTRODUCTION: Neonatal hyperbilirubinaemia, defined as a total serum bilirubin
      level above 5 mg/dL, is a frequent problem. This condition accounts for up to 75
      percent of hospital readmissions in the first week of life. The purpose of this
      study was to evaluate the aetiology of indirect hyperbilirubinaemia and the
      prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in newborns who
      were admitted to Vali-e-Asr Hospital in Zanjan City during the period 2001-2003.
      METHODS: Medical records of 376 newborns who had been admitted for management of
      indirect hyperbilirubinaemia were reviewed. All necessary information, including
      the results of G6PD activity test (expressed as unit per gramme haemoglobin),
      were recorded on standardised questionnaires. RESULTS: The subject group included
      159 (42.3 percent) boys and 217 (57.7 percent) girls. The prevalence of sepsis,
      ABO incompatibility, Rhesus incompatibility, and cephalhaematoma, G6PD deficiency
      was 15.7 percent (59 neonates), 3.7 percent (14 neonates), 2.1 percent (eight
      neonates), 0.5 percent (two neonates), and 2.1 percent (eight neonates),
      respectively. The median (interquartile range) of the highest total bilirubin
      level was 18 (15.8-20) mg/dL and 18.4 (16.3-19.5) mg/dL in normal G6PD and G6PD
      deficient newborns, respectively (p-value equals 0.7). CONCLUSION: We recommend
      performing G6PD testing in all Iranian and Mediterranean newborns with indirect
      hyperbilirubinaemia, unless other investigators ascertain and document that this
      is unnecessary as a routine test.

PMID- 17453101
TI  - Periprocedural complications associated with endovascular embolisation of
      intracranial ruptured aneurysms with matrix coils.
AB  - INTRODUCTION: Matrix is a type of bioactive coil expected to produce healing of
      cerebral aneurysms. We reviewed periprocedural complications associated with
      endovascular embolisation of ruptured intracranial aneurysms with matrix coils
      and evaluated the effects of matrix coils. METHODS: From October 2003 to
      September 2005, a total of 102 patients with 102 ruptured aneurysms and ten
      unruptured aneurysms underwent embolisations with matrix coils. We reviewed the
      medical records, radiographical studies and endovascular procedures to evaluate
      the morbidity and mortality related to ruptured aneurysm coiling. RESULTS: 16
      complications (15.7 percent) occurred, of which 14 were in the anterior
      circulation and two in the posterior circulation. Complications included nine
      intraprocedural ruptures (8.8 percent), three thromboembolism (2.9 percent), one
      coil migration (1.0 percent) and three parent vessel occlusions (2.9 percent).
      Six complications had no neurological consequences, three were with transient
      deficits, six resulted in persistent neurological deficits, and one caused the
      patient to die. No complication was associated with balloon remodelling
      technique, and coil migration occurred during one of the neuroform-assisted
      embolisations. Procedural-related neurological morbidity and mortality for all
      102 embolisations of ruptured aneurysms were 5.9 percent and 1.0 percent,
      respectively. CONCLUSION: Endovascular treatment of ruptured intracranial
      aneurysms with matrix coils is as safe as with bare platinum coils. Matrix coil
      does not increase the risk of thromboembolism. However, we must be cautious when
      we embolise small aneurysms with matrix coils, especially when the aneurysms are
      less than 5 mm in diameter.

PMID- 17453102
TI  - Ascites in the state of Qatar: aetiology and diagnostic value of ascitic fluid
      analysis.
AB  - INTRODUCTION: Ascites is common and represents an important feature of liver
      disease and other diseases. The aim of this study is to determine the causes of
      ascites in Qatar, and to evaluate the value of ascitic fluid analysis in
      different types of ascites. METHODS: This is a descriptive, prospective study of
      all patients admitted to the medical department at Hamad General Hospital with
      ascites between January 2004 and January 2005. RESULTS: Of the 104 patients
      enrolled in the study, 70 (67.3 percent) were males and 34 (32.7 percent) were
      females, with a mean age of 52.9 (+/-14.8) years. Liver cirrhosis was the most
      frequent cause of ascites in 62 patients (59.6 percent), while chronic alcoholism
      was the main cause of liver cirrhosis. Other frequent causes of ascites were
      malignant ascites in 12 patients (11.5 percent), malignancy-related ascites in
      ten patients (9.6 percent), and tuberculous peritonitis in eight patients (7.7
      percent). Based on the serum-ascites albumin gradient (SAAG), different causes of
      ascites were divided into two main groups. The first group was characterised by a
      mean SAAG of 1.1 or higher, and the second group was characterised by a mean SAAG
      of less than 1.1. The most common cause of high gradient ascites was liver
      cirrhosis, while the most common causes of low gradient ascites were
      carcinomatous peritonitis and tuberculous peritonitis. The mean ascitic lactate
      dehydrogenase (LDH) level was higher in cancer patients than in tuberculous
      patients (p-value is less than 0.05), while the mean ascitic glucose
      concentration was significantly lower in peritoneal tuberculosis than in
      carcinomatous peritonitis (p-value is less than 0.05). CONCLUSION: Liver
      cirrhosis is the main cause of ascites in Qatar. SAAG is a better distinguishing
      marker for separating ascites related to portal hypertension from other causes of
      ascites without portal hypertension. In patients with low gradient ascites,
      ascitic fluid glucose and LDH level are useful indicators for separating
      tuberculous from malignant ascites.

PMID- 17453103
TI  - Diagnostic markers in the structures of human biological liquids.
AB  - INTRODUCTION: To date, morphology research in laboratory diagnostics has referred
      only to cell tissues and excluded biological fluids. Our new technology is based
      on the study of structures of biological fluids formed during transition from
      liquid to solid state by dehydration under special conditions. These structures
      are formed due to the special "mosaic" configuration of molecules and
      microaggregates of the substance (protein and others) dissolved in the studied
      fluids. It should be considered as well that the specific structure of protein
      molecules is a fundamental basis of anatomical and physiological peculiarities of
      an organism. All pathological processes are initiated by the changes in the
      spatial configuration of protein molecules. METHODS: We have developed a special
      method named "cuneiform dehydration of biological liquids" to obtain thin films
      which possess specific structures. During the transition of a biological liquid
      into a solid, organic molecules build specific macrostructures in conformity with
      their configuration. RESULTS: Studies of the solid phase structures of different
      biological liquids allow us to find specific markers of various pathological
      processes in the human organism. In blood serum, we discovered markers of
      inflammation, sclerosis, chronic intoxication; in tear--markers of different
      stages of glaucoma; and in synovial fluid--markers of different stages of
      osteoarthrosis. In our investigation of 143 healthy people and 1,419 patients, a
      high rate of compliance of the discovered markers with the results of routine
      clinical and laboratory methods were observed. As the suggested technology has a
      higher sensitivity, the results obtained by this technology and routine methods
      do not always coincide. CONCLUSION: The developed technology gives new
      information about the state of the human organism and may be used in practice for
      diagnostics of various pathological processes and at pre-clinical studies of
      their development, as well as for the evaluation of the efficacy of medical
      treatment.

PMID- 17453104
TI  - Cytokine gene polymorphisms and the pathology of chronic gastritis.
AB  - INTRODUCTION: Helicobacter pylori (H. pylori) infection is associated with
      divergent clinical outcomes and these outcomes are largely influenced by the
      levels of cytokines in the gastric mucosa. The levels of these cytokines are
      dependant on cytokine gene polymorphisms. Pro-inflammatory cytokine polymorphisms
      are strongly associated with severe histological changes in the gastric mucosa in
      Caucasian populations. METHODS: In this study, we evaluated the role of cytokine
      gene polymorphisms in influencing the pathological severity of gastritis. 120
      patients were evaluated. Cytokine gene polymorphisms of interleukin-1 (IL-1)
      beta, tumour necrosis factor alpha and the IL-1 receptor antagonist genes were
      done using polymerase chain reaction (PCR) restriction fragment length
      polymorphism and PCR variable number of tandem repeats markers typed on the
      deoxyribonucleic acid obtained from the peripheral blood. Histological analysis
      was done by using the revised Sydney system. RESULTS: There was no association
      between pro-inflammatory cytokine gene polymorphisms and severity of gastritis.
      CONCLUSION: This data suggests that high cytokine levels are not seen in the
      gastric mucosa in Indians in spite of H. pylori colonisation. IL-1 beta is a
      potent proinflammatory cytokine which causes a partial clearance of the organism
      as well as hypochlorhydria. Corporal hypochlorhydria causes a persistent
      colonisation by H. pylori followed by the development of gastric atrophy and
      later carcinoma. This lack of association with a pro-inflammatory polymorphism
      suggests that only low levels of IL-1 beta are present in the gastric mucosa.
      This causes a low clearance of the organism and a high incidence of duodenal
      ulceration because of hyperchlorhydria. However, it is protective against the
      development of gastric carcinoma. This would explain the "Indian Paradox" of the
      apparent discrepancy of a high degree of colonisation by H. pylori and a low
      incidence of gastric carcinoma in the Indian population.

PMID- 17453105
TI  - Clinical usefulness of endoscopic ultrasonography-guided fine-needle aspiration
      in the diagnosis and staging of lung cancer.
AB  - Lung cancer is the most common cause of cancer-related mortality in Singapore,
      and accurate staging of lung cancer is therefore of paramount importance. Several
      non-invasive and invasive modalities can be used to stage lung cancer. Endoscopic
      ultrasonography-guided fine-needle aspiration (EUS-FNA) is a safe procedure that
      is performed under conscious sedation and has a sensitivity of up to 90-98
      percent in expert hands. In addition, nodal groups that are inaccessible by
      cervical mediastinoscopy (such as the aortopulmonary window lymph nodes) can be
      sampled by EUS-FNA. We present three cases in which EUS-FNA was used successfully
      to diagnose and stage lung cancer, thus avoiding surgery.

PMID- 17453106
TI  - Akinetic mutism after right internal watershed infarction.
AB  - We describe a 72-year-old man who developed akinetic mutism following a
      cerebrovascular accident involving his right internal watershed area and
      responded well to dopaminergic agonists. We discuss this rare condition and the
      unusual unilateral location of the lesion.

PMID- 17453107
TI  - Clinics in diagnostic imaging (116). Ruptured hepatocellular carcinoma.
AB  - A 37-year-old Chinese man with chronic hepatitis B, who frequently defaulted past
      follow-up appointments, was admitted for acute abdomen and shock. Computed
      tomography of the abdomen revealed a ruptured hepatocellular carcinoma involving
      the left lobe. After fluid resuscitation, gelfoam embolisation was performed to
      arrest the bleeding, followed by segmental resection of the hepatic lesion. There
      was aggressive recurrence following left segmental hepatectomy, and despite two
      courses of transarterial chemoembolisation, the patient died of local and
      pulmonary recurrences five months after his initial presentation. The management
      of hepatocellular carcinoma rupture is discussed.

PMID- 17453108
TI  - Electrocardiographical case. Elderly man with acute breathlessness. Atrial
      tachycardia with variable AV conduction block and transient hyperkalaemia-induced
      aberrant conduction.
AB  - A 67-year-old Chinese man presented to the emergency department with a history of
      abdominal bloating and shortness of breath. Initial electrocardiogram (ECG)
      showed atrial tachycardia (AT) with 2:1 atrioventricular (AV) conduction block.
      Six days after admission, he developed acute dyspnoea and confusion. Repeat ECG
      demonstrated a regular wide-complex tachycardia. Serum analysis revealed
      hyperkalaemia secondary to acute on chronic renal failure. Emergency treatment
      with intravenous calcium gluconate, 50% dextrose solution and short-acting
      insulin was instituted. The ECG promptly reverted to a narrow-complex AT with 2:1
      AV conduction block. The diagnosis and treatment of AT are discussed.

PMID- 17453109
TI  - Psychiatric morbidity in patients referred to an insomnia clinic.

PMID- 17453112
TI  - Can chlorpheniramine cause serotonin syndrome?

PMID- 17453113
TI  - Clinical spectrum of Parkinson's disease.

PMID- 17453115
TI  - Mucormycosis in patients with complicated cirrhosis.

PMID- 17453117
TI  - Published hospital bill sizes and healthcare costs: what was the effect of SARS?

PMID- 17453120
TI  - Determination of toxic metals in petroleum, cultivated land and ore samples using
      laser-induced breakdown spectroscopy.

PMID- 17453121
TI  - Tissue-related polychlorinated biphenyls accumulation in mediterranean cetaceans:
      assessment of toxicological status.

PMID- 17453122
TI  - Distribution and risk assessment of polycyclic aromatic hydrocarbons in household
      drinking water.

PMID- 17453123
TI  - Cadmium, lead, mercury and copper in fish from the Marmara Sea, Turkey.

PMID- 17453124
TI  - Bone density and breaking strength in UK raptors exposed to second generation
      anticoagulant rodenticides.

PMID- 17453125
TI  - N(2)O emissions under different moisture and temperature regimes.

PMID- 17453126
TI  - Association of cutis laxa and genital prolapse: a case report.
AB  - Cutis laxa (CL) is an extremely inherited or acquired connective tissue disorder
      characterised by a markedly reduced systemic elastin content. Genital
      abnormalities in patients with CL have been rarely reported. We report such a
      case in a 48-year-old CL patient affected by genital prolapse, focusing on
      immunohistological and molecular biology assessment of elastin and collagen type
      I, III, VI content in the main uterine ligaments. The woman was referred to our
      department for the onset of a rapidly progressing genital prolapse and urinary
      incontinence. The patient underwent total abdominal hysterectomy with bilateral
      salpingo-oophorectomy and sacrocolpopexy. Punch biopsies from both cardinal and
      uterosacral ligaments revealed a dramatic reduction in elastin and an increase in
      collagen type VI content. The present report seems to underline the central role
      exerted primarily by elastin in the supportive connective tissue and might
      contribute to the knowledge of extracellular matrix abnormalities at the basis of
      genital abnormalities in CL patients.

PMID- 17453127
TI  - Intentional single-stage revascularization of two different vascular beds in
      patients with vascular multimorbidity; a feasibility study.
AB  - AIMS: The aim of this retrospective study was to assess the feasibility of
      catheter-based interventions in two different vascular beds performed in a single
      stage in patients with vascular multimorbidity. METHODS AND RESULTS: Fifty
      patients, 28 males, mean age 68.6 (+/- 9.2) years and 22 females, mean ages 72.2
      (+/- 6.4) years were studied. At least one major cardiovascular risk factor was
      present in 48 (94%) of all patients. The most frequent combination of
      interventions was coronary artery disease (CAD) and renovascular disease (RVD)
      (20 patients, 40%) followed by CAD and peripheral artery disease (PAD) (17
      patients, 34%). In all patients technical success, defined as residual stenosis <
      or = 30% diameter, and procedural success, defined as lack of major adverse
      cardiac and cerebrovascular events (MACCE) during the in-hospital period, were
      achieved. In two patients surgical revision of the access site was required and
      in two additional patients minor local bleeding was observed. CONCLUSIONS:
      Sequential vascular interventions in different vascular beds may be performed in
      a single stage with high success rates, however, compared to historical controls
      possibly at a higher rate of access site complications. A larger study using
      controls is needed to assess the medical benefits and cost efficacy of a single
      stage approach in patients with clinically relevant vascular multimorbidity.

PMID- 17453128
TI  - Quantitating loss of life by smoking a single cigarette.

PMID- 17453129
TI  - Late relapse of Q fever endocarditis.

PMID- 17453131
TI  - Coronary plaque classification using intravascular ultrasound -- radiofrequency
      analysis in a patient with severe coronary vasospasm.

PMID- 17453130
TI  - Novel insights into an old controversy: is coronary artery ectasia a variant of
      coronary atherosclerosis?
AB  - Coronary artery ectasia (CAE) is defined as a localized or diffuse non
      obstructive lesion of the epicardial coronary arteries with a luminal dilation
      exceeding 1.5-fold the diameter of the normal adjacent arterial segment. The
      incidence of CAE has been reported to range between 2% and 4%, which might be an
      overestimation of the true frequency. The coincidence of CAE with other systemic
      vascular dilatations has suggested that the mechanism underlying CAE is not only
      localized to coronary arteries, but also to other vascular compartments such as
      aorta or peripheral veins. Although the pathophysiology of CAE remains largely
      unknown, it was supposed to represent a variant of coronary atherosclerosis. This
      review focuses on this controversy of whether CAE and coronary artery disease
      (CAD) are two manifestations of the same underlying process. There are clear
      differences between CAD and CAE with respect to cardiovascular risk factors such
      as diabetes mellitus, and pathogenic steps in disease progress such as
      inflammation or extracellular matrix remodeling. As this review will underscore,
      the current knowledge of the field is insufficient to finally clarify the
      causative interrelation between CAE and CAD. The clinical course and treatment of
      CAE mainly depends on its coexistence with CAD. When coexisting with CAD, the
      prognosis and treatment of CAE are the same as for CAD alone. In isolated CAE,
      prognosis is better and anti-platelet drugs are the mainstay of treatment.
      Surgical treatment can be considered in selected patients. For clarifying the
      mechanism underlying CAE, additional clinical, histopathological and
      pathophysiological investigations are required. In fact, every patient with CAE
      should be evaluated systematically for pathological changes in other vascular
      territories, both in the arterial system as well as in the venous system, which
      might occur in the disease process.

PMID- 17453132
TI  - Improvement of the primary success rate of recanalization of chronic total
      coronary occlusions with the Safe-Cross system after failed conventional wire
      attempts.
AB  - BACKGROUND: In view of the improved long-term patency with drug-eluting stents,
      the challenge with chronic total coronary occlusion (CTO) remains the low primary
      success rate. Improved guide wires have increased this rate, but alternative
      devices may be of additional value. The goal of the present study was to
      determine the additional benefit of a new penetration device in CTOs after an
      extensive conventional wire approach. METHODS AND RESULTS: In 148 consecutive
      patients the recanalization of a CTO of >3 months was attempted. A conventional
      wire approach was used with recent dedicated recanalization wires, which was
      successful in 104 patients (70%). If after at least 20 min of fluoroscopic time
      no crossing of the wire was achieved, the Safe-Cross wire (SC) (Intralumina) was
      used which enables verification of the intraluminal wire position via optical
      reflectometry, and crossing of resistent occlusion caps by radiofrequency
      ablation. Due to severe dissections after the conventional approach, the SC was
      not used in 10 patients. In 34 patients the SC wire was applied, leading to
      successful lesion crossing in 14 patients (41%). Thus, the primary success rate
      was improved from 70.2% to 79.7%. No periprocedural major adverse events were
      observed with the SC wire. The successful attempts with the SC wire were
      predominantly in blunt occlusions. All patients with successful wire passage
      could be treated with one or more stents. CONCLUSIONS: In a real world cohort of
      patients with CTO, the SC wire could increase the primary success rate after
      failed extensive conventional wire attempt. In these worst case patients the SC
      success rate was 41%. This new wire appears to have additional potential in
      failures of a conventional wire approach.

PMID- 17453133
TI  - Partial anomalous pulmonary venous drainage of the left upper pulmonary vein --
      catheter interventional treatment is sometimes possible.

PMID- 17453134
TI  - Transient sirolimus serum levels after implantation of a sirolimus eluting stent
      in an infant.

PMID- 17453135
TI  - Interatrial lipoma: catheter ablation of an atrial tachycardia originating from a
      dislodged arrhythmogenic substrate assisted by a three-dimensional mapping system
      with a combined synchronized three-dimensional CT reconstruction.

PMID- 17453136
TI  - Inappropriate implantable cardioverter-defibrillator shock induced by
      electromagnetic interference while taking a shower.

PMID- 17453137
TI  - Percutaneous coronary interventions in Europe: prevalence, numerical estimates,
      and projections based on data up to 2004.
AB  - AIMS: A registry mandated by the European Society of Cardiology collects data on
      trends in interventional cardiology within Europe. Special interest focuses on
      relative increases and ratios in new techniques and their distributions across
      Europe. We report the data through 2004 and give an overview of the development
      of coronary interventions since the first data collection in 1992. METHODS AND
      RESULTS: Questionnaires were distributed yearly to delegates of all national
      societies of cardiology represented in the European Society of Cardiology. The
      goal was to collect the case numbers of all local institutions and operators. The
      overall numbers of coronary angiographies increased from 1992 to 2004 from 684
      000 to 2 238 000 (from 1250 to 3930 per million inhabitants). The respective
      numbers for percutaneous coronary interventions (PCIs) and coronary stenting
      procedures increased from 184 000 to 885 000 (from 335 to 1550) and from 3000 to
      770 000 (from 5 to 1350), respectively. Germany was the most active country with
      712 000 angiographies (8600), 249 000 angioplasties (3000), and 200 000 stenting
      procedures (2400) in 2004. The indication has shifted towards acute coronary
      syndromes, as demonstrated by rising rates of interventions for acute myocardial
      infarction over the last decade. The procedures are more readily performed and
      perceived safer, as shown by increasing rate of "ad hoc" PCIs and decreasing need
      for emergency coronary artery bypass grafting (CABG). In 2004, the use of drug
      eluting stents continued to rise. However, an enormous variability is reported
      with the highest rate in Switzerland (70%). If the rate of progression remains
      constant until 2010 the projected number of coronary angiographies will be over
      three million, and the number of PCIs about 1.5 million with a stenting rate of
      almost 100%. CONCLUSION: Interventional cardiology in Europe is ever expanding.
      New coronary revascularization procedures, alternative or complementary to
      balloon angioplasty, have come and gone. Only stenting has stood the test of time
      and matured to the default technique. Facilitated access to PCI, more complete
      and earlier detection of coronary artery disease promise continued growth of the
      procedure despite the uncontested success of prevention.

PMID- 17453138
TI  - Perceived psychosocial stress and cardiovascular risk factors in obese and non
      obese patients.
AB  - BACKGROUND: Patients after their first myocardial infarction are characterized by
      increased levels of perceived stress and abdominal obesity compared to a matched
      control group. In the setting of primary prevention, the association of stress
      and cardiovascular risk factors in obese and non-obese individuals is not known.
      METHODS AND RESULTS: For this prospective cross-sectional study, primary care
      physicians recruited consecutive patients with BMI >30 and the next two
      individuals presenting with a BMI < 30 as controls (n=414). The 10-year risk of
      death from cardiovascular disease determined by the European Society of
      Cardiology HeartScore Germany was associated with BMI (p<0.0001). However, waist
      circumference and waist-to-hip ratio predicted the calculated cardiovascular risk
      better than BMI. Psychosocial risk factors were determined using the INTERHEART
      questionnaire. Obesity was positively associated with depression (p=0.005) but
      not with perceived stress. In contrast to obesity or depression, the extent of
      perceived general stress inversely correlated with cardiovascular risk (never
      stress: 4.4+/-2.8%, some period: 2.4+/-2.7%, several periods: 1.4+/-2.3% and
      permanent: 0.65+/-0.5%; p=0.0001). Similarly, additional parameters of stress
      (stress at home, stress at work, financial stress, stressful life events) as well
      as locus of control were inversely associated with cardiovascular risk factors. A
      medical history of general stress was correlated with younger age and increased
      smoking. CONCLUSIONS: Waist to hip ratio powerfully predicts the cardiovascular
      risk estimated by HeartScore in primary prevention. Perceived stress assessed by
      a standardized questionnaire does not positively correlate with traditional
      cardiovascular risk factors and warrants further evaluation as a routine tool for
      primary care physicians.

PMID- 17453139
TI  - Takotsubo cardiomyopathy with an unusual pattern of regional left ventricular
      wall motion abnormalities.

PMID- 17453140
TI  - Low-grade albuminuria and cardiovascular risk : what is the evidence?
AB  - Microalbuminuria (MA), conventionally defined as a urinary albumin excretion
      (UAE) of 30-300 mg/day, is recognised as a marker of endothelial dysfunction.
      Furthermore, it represents an established risk factor for cardiovascular
      morbidity and mortality and for end-stage renal disease in individuals with an
      adverse cardiovascular risk profile. It is common in the general population,
      particularly in patients with diabetes mellitus or arterial hypertension. There
      is growing evidence from prospective observational trials that UAE levels well
      below the current MA threshold ("lowgrade MA") are also associated with an
      increased risk of incident cardiovascular disease and allcause mortality. Even in
      apparently healthy individuals (without diabetes or hypertension), such an
      association has been shown. As albuminuria screening assays that are reliable
      even in the lower ranges are commercially available, there may be an important
      clinical role for MA in disease screening, comparable to the role of blood
      pressure and lipid screening. MA is modifiable, and the inhibition of the renin
      angiotensin system by ACE inhibitors and AT1 receptor antagonists has been shown
      to result in a lower incidence of cardiovascular events.

PMID- 17453141
TI  - Cardiospecificity of the 3rd generation cardiac troponin T assay during and after
      a 216 km ultra-endurance marathon run in Death Valley.
AB  - BACKGROUND: The reasons for the appearance of cardiacspecific troponin (cTnT)
      after strenuous exercise are unclear. The aim of the present study was to
      evaluate the cardiospecificity of the 3(rd) generation cardiac cTnT assay during
      and after an ultra-endurance race of 216 km at extreme environmental conditions
      in Death Valley. STUDY DESIGN AND METHODS: We measured serially cTnT, creatine
      kinase (CK), activity and mass of the isoenzyme MB of CK (CK-MB(act) and CK
      MB(mass)), and myoglobin in 10 well-trained athletes before, repeatedly during
      and after the race. RESULTS: Six of 10 participants finished the race within a
      preset time of 60 hours. Postrace values of biochemical markers CK, CK-MB(act),
      CKMB(mass), and myoglobin were significantly increased compared to baseline
      (p<0.05). CK-MB(act) increased from (median (25(th)/ 75(th)percentile) 12 (10/13)
      U/L to 72 (32/110) U/L, CK-MB(mass) from 3.9 (2.9/5.6) U/L to 65 (18/80) U/L and
      CK increased from median 136 (98/ 228) U/L to 3,570 (985/6,884) U/L respectively.
      Pre-race myoglobin was 27 (22/31) microg/l compared to 530 (178/657) microg/l
      after the run. One runner developed significant exercise-induced rhabdomyolysis
      with spontaneous recovery. cTnT values remained below the 99(th) percentile
      reference limit in all athletes including the runner who developed significant
      rhabdomyolysis (peak CK 27,951 U/L). CONCLUSIONS: Strenuous endurance exercise,
      even under extreme environmental conditions, does not result in structural
      myocardial damage in well-trained ultra-endurance athletes. We found no
      crossreactivity between cTnT and CK, neither in exercise-induced skeletal muscle
      trauma nor after rhabdomyolysis underscoring the excellent analytical performance
      of 3(rd) generation cTnT assay.

PMID- 17453142
TI  - The corticotropin-releasing factor (CRF) family of peptides as local modulators
      of adrenal function.
AB  - Corticotropin-releasing factor (CRF), also termed corticotropin-releasing hormone
      (CRH) or corticoliberin, is the major regulator of the adaptive response to
      internal or external stresses. An essential component of the adaptation mechanism
      is the adrenal gland. CRF regulates adrenal function indirectly through the
      central nervous system (CNS) via the hypothalamic-pituitary-adrenal (HPA) axis
      and via the autonomic nervous system by way of locus coeruleus (LC) in the brain
      stem. Accumulating evidence suggests that CRF and its related peptides also
      affect the adrenals directly, i.e. not through the CNS but from within the
      adrenal gland where they form paracrine regulatory loops. Indeed, CRF and its
      related peptides, the urocortins (UCNs: UCN1, UCN2 and UCN3), their receptors CRF
      type 1 (CRF(1)) and 2 (CRF(2)) as well as the endogenous pseudo-receptor CRF
      binding protein (CRF-BP) are all expressed in adrenal cortical, medullary
      chromaffin and resident immune cells. The intra-adrenal CRF-based regulatory
      system is complex and depends on the balance between the local concentration of
      CRF ligands and the availability of their receptors.

PMID- 17453143
TI  - Molecular mechanisms of nitrosative stress-mediated protein misfolding in
      neurodegenerative diseases.
AB  - Nitrosative and oxidative stress, associated with the generation of excessive
      reactive oxygen or nitrogen species, are thought to contribute to
      neurodegenerative disorders. Many such diseases are characterized by
      conformational changes in proteins that result in their misfolding and
      aggregation. Accumulating evidence implies that at least two pathways affect
      protein folding: the ubiquitin-proteasome system (UPS) and molecular chaperones.
      Normal protein degradation by the UPS can prevent accumulation of aberrantly
      folded proteins. Molecular chaperones - such as protein-disulfide isomerase,
      glucose-regulated protein 78, and heat shock proteins - can provide
      neuroprotection from aberrant proteins by facilitating proper folding and thus
      preventing their aggregation. Our recent studies have linked nitrosative stress
      to protein misfolding and neuronal cell death. Here, we present evidence for the
      hypothesis that nitric oxide contributes to degenerative conditions by S
      nitrosylating specific chaperones or UPS proteins that would otherwise prevent
      accumulation of misfolded proteins.

PMID- 17453144
TI  - RNA and protein-dependent mechanisms in tauopathies: consequences for therapeutic
      strategies.
AB  - Tauopathies are a group of neurodegenerative diseases characterised by
      intracellular deposits of the microtubule-associated protein tau. The most
      typical example of a tauopathy is Alzheimer's disease. The importance of tau in
      neuronal dysfunction and degeneration has been demonstrated by the discovery of
      dominant mutations in the MAPT gene, encoding tau, in some rare dementias. Recent
      developments have shed light on the significance of tau phosphorylation and
      aggregation in pathogenesis. Furthermore, emerging evidence reveals the central
      role played by tau pre-mRNA processing in tauopathies. The present review focuses
      on the current understanding of tau-dependent pathogenic mechanisms and how
      realistic therapies for tauopathies can be developed.

PMID- 17453145
TI  - How do Shp2 mutations that oppositely influence its biochemical activity result
      in syndromes with overlapping symptoms?
AB  - Activating and inactivating mutations of SHP-2 are responsible, respectively, for
      the Noonan (NS) and the LEOPARD (LS) syndromes. Clinically, these developmental
      disorders overlap greatly, resulting in the apparent paradox of similar diseases
      caused by mutations that oppositely influence SHP-2 phosphatase activity. While
      the mechanisms remain unclear, recent functional analysis of SHP-2, along with
      the identification of other genes involved in NS and in other related syndromes
      (neurofibromatosis-1, Costello and cardio-facio-cutaneous syndromes), strongly
      suggest that Ras/MAPK represents the major signaling pathway deregulated by SHP-2
      mutants. We discuss the idea that, with the exception of LS mutations that have
      been shown to exert a dominant negative effect, all disease-causing mutations
      involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced
      MAPK activation. This suggests that a narrow range of MAPK signaling is required
      for appropriate development. We also discuss the possibility that LS mutations
      may not simply exhibit dominant negative activity.

PMID- 17453146
TI  - Loss of heterozygosity studies in extracranial metastatic meningiomas.
AB  - Although most meningiomas are slow-growing tumours associated with favourable
      prognosis, they often present local recurrence after surgical treatment; by
      contrast, extracranial metastatic meningiomas are rare, occurring in less than 1%
      of the cases. Risk factors for distal spread remain largely unknown. We report
      three cases with lung or bone metastases from intracranial recurrent meningiomas.
      Loss of heterozygosity (LOH) analysis on 1p, 9p, 10q, 14q, and 22q was conducted
      in available primary, recurrent and metastatic lesions, showing the same LOH
      pattern in the distal metastases and in the intracranial meningioma. LOH at 1p,
      14q and 9p, known to be associated with increased aggressiveness, were found. The
      results highlight the potential clinical relevance of integrating
      histopathological studies with molecular genetic analysis in the follow-up of
      patients with different types of meningiomas.

PMID- 17453147
TI  - All-trans-retinoic acid induces cell growth arrest in a human medulloblastoma
      cell line.
AB  - Medulloblastomas (MBs) are the most common malignant brain tumors of childhood.
      Antitumor agents promoting long-term survival with limited toxicities are thus
      far lacking. Preliminary findings suggest that retinoic acid (RA) derivatives
      (retinoids) exert antitumor effects by inhibiting cell proliferation and inducing
      cell differentiation, apoptosis, and growth arrest, and RAs have been
      specifically shown to induce apoptosis in some MB cells. However, there is no
      conclusive evidence of retinoids inducing cell growth arrest in MBs. The aim of
      this study is to investigate whether retinoids play a role in cell-cycle arrest
      of MB cells. All-trans-retinoic acid (ATRA) was selected for these studies as it
      is known to have the capacity of inducing cell cycle arrest and apoptosis in
      other types of cancer cells. Three MB cell lines (DAOY, D283 and D341) were
      subjected to ATRA treatment. The proportions of cells in the G0/G1 phase of cell
      cycle and in apoptosis were evaluated. The results showed that cell growth
      arrest, rather than apoptosis, was the main mechanism by which RA inhibited cell
      proliferation in the MB cell line DAOY, but not in the others (D283 and D341).
      Decreased expression of CyclinD1 and C-myc which regulate the transition of cell
      cycle was observed in DAOY cells following drug treatment, suggesting that these
      genes might be involved in ATRA retardation of cell cycle progression. Expression
      of RARbeta, a mediator of the action of retinoids, was also induced by RA in DAOY
      cells, implying that RAR-beta might also be involved in the mechanism of RA
      induced cell cycle arrest. In conclusion, we have provided evidence for the first
      time that RA may induce cell cycle arrest in vitro in DAOY MB cells via
      inhibition of CyclinD1 or C-myc.

PMID- 17453148
TI  - Discovery of serum biomarkers in astrocytoma by SELDI-TOF MS and proteinchip
      technology.
AB  - OBJECTIVE: To discover serum biomarkers in astrocytoma patients for early
      detection of glioma and evaluation of prognosis. METHODS: A total of 140 serum
      samples were analyzed using the weak cation-exchange (WCX) chips. Among those, 73
      were sera from astrocytoma patients, 56 from normal controls, and 11 from other
      brain tumors. For building a diagnosis model, the samples were randomly split
      into a training set and a test set with similar distribution of case and control
      samples. Proteomics profiles were obtained using a PBSII instrument and the data
      were analyzed with the accompanying software. RESULTS: Seven serum biomarkers
      were significantly deregulated in astrocytoma group comparing to the normal
      control group. Among them, four were up-regulated and three were down-regulated.
      A decision tree classification method were developed using these seven markers. A
      sensitivity of 84.6% and a selectivity of 84.6% were achieved to discriminate
      astrocytoma from normal controls. In addition, a correlation of these markers
      with the astrocytoma malignancy was observed. CONCLUSIONS: Proteomics approaches
      such as SELDI-TOF mass spectrometry could greatly facilitate the discovery of
      serum biomarkers in astrocytoma. The discovered biomarkers might show great
      potential for early detection of astrocytoma and evaluation of prognosis for
      those clinical suspect astrocytoma patients. However, this need warrant further
      study.

PMID- 17453149
TI  - Dexamethasone inhibits proliferation and stimulates ecto-5'-nucleotidase/CD73
      activity in C6 rat glioma cell line.
AB  - Malignant gliomas are the most common and devastating primary tumors of the adult
      central nervous system. Dexamethasone, a synthetic glucocorticoid, is commonly co
      administered to control edema in the management of brain tumors during
      chemotherapy and radiotherapy. In the present study, the effect of dexamethasone
      on proliferation and ectonucleotidase activities in rat C6 glioma cell line was
      investigated. Dexamethasone concentrations ranging from 0.001 to 10 microM
      induced a time- and concentration-dependent inhibition of C6 rat glioma cell
      proliferation after 24, 48 and 72-h treatment. The tetrazolium reduction assay
      (MTT) indicated a reduction of in cell viability (44 +/- 7.6%) after 48-h
      treatment with 1 microM dexamethasone. Pretreatment with 10 microM of RU38486, an
      antagonist of glucocorticoid receptors, abolished the effect of 1 microM
      dexamethasone by 78 +/- 9.8% after 48 h of treatment, indicating that this action
      is mediated via the glucocorticoid receptor. Members of the E-NTPDase family and
      ecto-5'-nucleotidase/CD73 can modulate extracellular ATP degradation and
      adenosine formation, both of which have been described as proliferation factors.
      Treatment of C6 glioma cells for 48 h with 1 microM dexamethasone increased in 38
      +/- 8.09% the AMP hydrolysis and in 3.7-fold the ecto-5'-nucleotidase/CD73
      expression, suggesting an increase in adenosine formation and, therefore, a
      possible modulatory role in the elicitation of cell death responses. In addition,
      pretreatment with 5 microM GF 109203X, a protein kinase C (PKC) inhibitor,
      abolished the effect of dexamethasone on cell proliferation and on ecto-5'-NT
      activity, suggesting that dexamethasone could exert this action via PKC. The
      alterations in the catabolism of extracellular purines induced by dexamethasone
      treatment in glioma C6 cells could be related to its pharmacological effects.

PMID- 17453150
TI  - Signal transduction in monocytes: the role of zinc ions.
AB  - The availability of zinc has a regulatory role in the immune system. It can have
      either pro- or anti-inflammatory effects, which both seem to be a consequence of
      a direct interaction of zinc with the cytokine secretion by monocytes. In this
      review, the molecular basis for this effect, the interaction of zinc with the
      signal transduction of monocytes, is discussed. In particular, zinc seems to
      activate or inhibit several signaling pathways that interact with the signal
      transduction of pathogen sensing receptors, the so-called Toll-like receptors
      (TLR), which sense pathogen-derived molecular structures and, upon activation,
      lead to secretion of pro-inflammatory cytokines. The interaction of zinc with
      protein tyrosine phosphatases and protein kinase C, and a direct modulation of
      lipopolysaccharide binding to its receptor (TLR-4) all result in enhanced
      cytokine production. On the other hand, a complex interaction between zinc, NO
      and cyclic nucleotide signaling, and inhibition of interleukin-1 receptor
      associated kinase-1, and inhibitor of kappa B kinase all counteract the
      production of pro-inflammatory cytokines. A role for the zinc binding protein
      metallothionein as a regulator for intracellular zinc signaling is discussed. By
      acting on all these signaling molecules, the zinc status of monocytes can have a
      direct effect on inflammation.

PMID- 17453151
TI  - Two-year results of intravitreal triamcinolone acetonide injection for the
      treatment of diabetic macular edema.
AB  - PURPOSE: To investigate 2-year results of intravitreal triamcinolone acetonide
      injection for the treatment of diffuse diabetic macular edema unresponsive to
      previous laser photocoagulation. METHOD: The study included 75 eyes of 75
      diabetic patients with clinically significant diffuse macular edema that had
      failed to respond to previous laser photocoagulation. An intravitreal injection
      of triamcinolone acetonide at the dose of 4 mg/0.1 ml was administered. Best
      corrected visual acuity was measured as the logarithm of the minimum angle of
      resolution (logMAR), and central macular thickness was obtained by optical
      coherence tomography at each visit. Intraocular pressure and lenticular status
      were also evaluated. Differences among measurements were evaluated by Friedman
      two-way analysis of variance by ranks. Mean follow-up period was 24.7 +/- 5.9
      months. RESULTS: The mean central macular thickness, which was obtained 3 days, 1
      month, 3 months, 6 months, 9 months, 12 months, 18 months and 24 months
      postoperatively, was significantly different from the baseline measurement (P <
      0.001). Mean best-corrected logMAR visual acuity improved significantly from
      baseline at the 1- month and 3-month follow-up intervals (P < 0.05), but there
      was no significant change at the 6- month, 9-month, 12-month, 18-month or 24
      month follow-up periods (P > 0.05). During the follow-up, 29 (38.7%) eyes
      received re-injection of intravitreal triamcinolone. Twenty-one (28%) eyes
      developed intraocular pressure values higher than 21 mmHg, and 18 (24%) eyes
      developed cataract. Thirteen (17.3%) eyes required cataract and/or glaucoma
      surgery. CONCLUSIONS: In refractory diabetic macular edema, intravitreal
      triamcinolone effectively reduces foveal thickness and improves visual acuity in
      the short term, but with the extended follow-up, the number of recurrences and
      steroid-related complications were shown to increase. Nevertheless, it may be a
      therapeutic option in some patients that do not respond to previous laser
      photocoagulation.

PMID- 17453152
TI  - Microbial keratitis in West Anatolia, Turkey: a retrospective review.
AB  - PURPOSE: To analyze the clinical and microbiological characteristics of microbial
      keratitis in West Anatolia, Turkey during a 16-year period. METHODS: This is a
      retrospective study in which medical records were reviewed for all eyes with
      clinically diagnosed microbial keratitis presenting at the Izmir Ataturk Training
      and Research Hospital from January 1990 to December 2005. Risk factors, microbial
      isolations and clinical features were analyzed. RESULTS: Microbial keratitis was
      diagnosed for 620 eyes in 620 patients (250 women and 370 men; mean age: 54.13
      years +/- 20.06). Pathogens from cultures were identified for 225 eyes (36.2%)
      and included Gram-negative (8.9%) and Gram-positive micro-organisms (68.8%) and
      fungi (22.3%). Staphylococcus epidermidis was the most commonly isolated micro
      organism (26.6%), followed by S. aureus (24.4%), Streptococci pneumoniae (15.5%),
      fungi (22.3%), Pseudomonas species (6.6%), Enterobacter (2.2%) and
      Corynebacterium (2.2%). Ocular trauma was the most common predisposing factor
      (26.6%). Mean duration from onset of symptoms to diagnosis was 11.68 +/- 11.29
      days. CONCLUSION: Staphylococci are the most commonly isolated microbial agents
      in cases of infectious keratitis in West Anatolia, Turkey. These findings will
      provide valuable background information and facilitate successful treatment in
      this region, and they will be useful as reference data for the particular
      population in this region as a basis for empirical antibiotic therapy.

PMID- 17453153
TI  - Congenital cystic eye with intracranial anomalies: a clinicopathologic study.
AB  - PURPOSE: To describe clinical, imaging and histopathologic findings of congenital
      cystic eyes associated with intracranial malformations. METHODS: Retrospective,
      noncomparative, interventional, clinicopathologic case reports of two female
      children (ages 15 days and six months) who were found to have non-discernable eye
      globes at birth. The patients underwent complete clinical examination, imaging
      studies, surgical exploration and histopathological evaluation of the excised
      orbital cystic structures. RESULTS: The fellow socket in one patient was found to
      be anophthalmic and the fellow eye in the second patient was highly myopic.
      Clinical, imaging [ultrasonography, computerized tomography (CT) scan and
      magnetic resonance imaging (MRI)], and histopathologic evaluations were
      consistent with the diagnosis of congenital cystic eye in both cases.
      Intracranial abnormalities were found in both patients, requiring
      ventroperitoneal shunting. Orbital cysts in both patients were excised and no
      recognizable eye structures were identified at the time of surgery.
      Histopathologic study in each case revealed a cyst externally surrounded by dense
      fibrous connective tissue with the inner aspect of the cyst lined by primitive
      neuroglial tissue in one case and immature and dysplastic retinal elements in the
      other. No recognizable ocular structures or microphthalmos were identified in
      either case. Immunohistochemical staining for glial fibrillary acidic protein,
      neuron-specific enolase and neurofilament protein were positive without evidence
      of normal elements of cornea, lens, ciliary body, choroid or retina. CONCLUSION:
      Congenital cystic eye should be suspected in patients with an unrecognizable eye
      globe and the possible association with intracranial malformation investigated.
      Early recognition of the association may help in the diagnosis and treatment of
      anophthalmic socket and intracranial anomalies.

PMID- 17453154
TI  - Improved drought tolerance without undesired side effects in transgenic plants
      producing trehalose.
AB  - Most organisms naturally accumulating trehalose upon stress produce the sugar in
      a two-step process by the action of the enzymes trehalose-6-phosphate synthase
      (TPS) and trehalose-6-phosphate phosphatase (TPP). Transgenic plants
      overexpressing TPS have shown enhanced drought tolerance in spite of minute
      accumulation of trehalose, amounts believed to be too small to provide a
      protective function. However, overproduction of TPS in plants has also been found
      combined with pleiotropic growth aberrations. This paper describes three
      successful strategies to circumvent such growth defects without loosing the
      improved stress tolerance. First, we introduced into tobacco a double construct
      carrying the genes TPS1 and TPS2 (encoding TPP) from Saccharomyces cerevisiae.
      Both genes are regulated by an Arabidopsis RuBisCO promoter from gene AtRbcS1A
      giving constitutive production of both enzymes. The second strategy involved
      stress-induced expression by fusing the coding region of ScTPS1 downstream of the
      drought-inducible Arabidopsis AtRAB18 promoter. In transgenic tobacco plants
      harbouring genetic constructs with either ScTPS1 alone, or with ScTPS1 and ScTPS2
      combined, trehalose biosynthesis was turned on only when the plants experienced
      stress. The third strategy involved the use of AtRbcS1A promoter together with a
      transit peptide in front of the coding sequence of ScTPS1, which directed the
      enzyme to the chloroplasts. This paper confirms that the enhanced drought
      tolerance depends on unknown ameliorated water retention as the initial water
      status is the same in control and transgenic plants and demonstrates the
      influence of expression of heterologous trehalose biosynthesis genes on
      Arabidopsis root development.

PMID- 17453155
TI  - UDN glycoprotein inhibits activator protein-1 and matrix metalloproteinase-9 via
      blocking of oxygen radicals in HT-29 cells.
AB  - The present study was performed to investigate the anti-inflammatory potential of
      a 116-kDa glycoprotein isolated from Ulmus davidiana Nakai (UDN glycoprotein) in
      lipopolysaccaride (LPS)-treated cancerous human colon epithelial cells (HT-29
      cells). UDN glycoprotein inhibited the production of intracellular superoxide
      anion (O (2) (.-) ), hydrogen peroxides (H(2)O(2)), and nitric oxide (NO),
      whereas normalized the activity of anti-oxidant enzymes [superoxide dismutase
      (SOD), catalase (CAT), and glutathione peroxidase (GPX)], accompanying the
      inhibition of manganese-superoxide dismutases (Mn-SOD) activity in LPS-treated HT
      29 cells. In addition, UDN glycoprotein blocked the DNA binding activity of
      activator protein-1 (AP-1) through suppression of c-Jun and c-Fos activities,
      respectively. We also evaluated the anti-inflammatory potential of UDN
      glycoprotein based on the activity of the pro-inflammatory signal mediators
      [inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and matrix
      metalloproteinases-9 (MMP-9)]. The results showed that UDN glycoprotein (200
      mug/ml) has an inhibitory effect on the activation of iNOS, COX-2, and MMP-9
      proteins in the LPS-treated HT-29 cells. From these results, we suggest that UDN
      glycoprotein is one of the potential anti-inflammatory agents that blocks LPS
      mediated inflammatory signal pathway in HT-29 cells. Here, we speculate that UDN
      glycoprotein could be used as an antioxidative agent for inflammatory
      gastrointestinal cancers.

PMID- 17453156
TI  - The permeability transition pore in cell death.
AB  - The permeability transition pore (PT-pore) is a multi-component protein aggregate
      in mitochondria that comprises factors in the inner as well as in the outer
      mitochondrial membrane. This complex has two functions: firstly, it regulates the
      integration of oxidative phosphorylation into the cellular energy household and
      secondly, it induces cell death when converted into an unspecific channel. The
      latter causes a collapse of the mitochondrial membrane potential and activates a
      chain of events that culminate in the demise of the cell. It has been
      controversial for some time whether the PT-pore is causative for or only
      amplifies a signal of cell death but novel results confirm a central role of this
      protein complex for cell death induction. While a considerable body of data exist
      on its subunit composition, recent genetic knock-out experiments suggest that the
      identity of the core factors of the PT-pore is still unresolved. Moreover,
      accumulating evidence point to a much more complex composition of this protein
      complex than anticipated. Here, we review the current knowledge of its subunit
      composition, the evidence of a role in cell death, and we propose a model for the
      activation of the PT-pore for cell death.

PMID- 17453157
TI  - Mitochondrial carriers and pores: key regulators of the mitochondrial apoptotic
      program?
AB  - Mitochondria play a pivotal role in the process of apoptosis. Alterations in
      mitochondrial structure and function during apoptosis are regulated by proteins
      of the BCL-2 family, however their exact mechanism of action is largely unknown.
      Mitochondrial carriers and pores play an essential role in maintaining the normal
      function of mitochondria, and BCL-2 family members were shown to interact with
      several mitochondrial carriers/pores and to affect their function. This review
      focuses on the involvement of several of these mitochondrial carriers/pores in
      the regulation of the mitochondrial death pathway.

PMID- 17453158
TI  - Bax activation and mitochondrial insertion during apoptosis.
AB  - The mitochondrial apoptotic pathway is a highly regulated biological mechanism
      which determines cell fate. It is defined as a cascade of events, going from an
      apoptotic stimulus to the MOM permeabilization, resulting in the activation of
      the so-called executive phase. This pathway is very often altered in cancer
      cells. The mitochondrial permeabilization is under the control of the Bcl-2
      family of proteins (pBcls). These proteins share one to four homology domains
      (designed BH1-4) with Bcl-2, and are susceptible of homo- and/or hetero
      dimerization. In spite of a poor amino-acid sequence homology, these proteins
      exhibit very similar tertiary structures. Strikingly, while some of these
      proteins are anti-apoptotic, the others are pro-apoptotic. Pro-apoptotic proteins
      are further divided in two sub-classes: multi-domains proteins, among which Bax
      and Bak, which exhibit BH1-3 domains, and BH3-only proteins (or BOPs).
      Schematically, BOPs and anti-apoptotic proteins antagonistically regulate the
      activation of the multi-domain proteins Bax and Bak and their oligomerization in
      the MOM, the latter process being responsible for the apoptotic mitochondrial
      permeabilization. Considering the critical role of Bax in cancer cells apoptosis,
      we focus in this review on the molecular events of Bax activation through its
      interaction with the other proteins from the Bcl-2 family. The mechanism by which
      Bax triggers the MOM permeabilization once activated will be discussed in some
      other reviews in this special issue.

PMID- 17453160
TI  - Mitochondria, oxidative stress and cell death.
AB  - In addition to the well-established role of the mitochondria in energy
      metabolism, regulation of cell death has recently emerged as a second major
      function of these organelles. This, in turn, seems to be intimately linked to
      their role as the major intracellular source of reactive oxygen species (ROS),
      which are mainly generated at Complex I and III of the respiratory chain.
      Excessive ROS production can lead to oxidation of macromolecules and has been
      implicated in mtDNA mutations, ageing, and cell death. Mitochondria-generated ROS
      play an important role in the release of cytochrome c and other pro-apoptotic
      proteins, which can trigger caspase activation and apoptosis. Cytochrome c
      release occurs by a two-step process that is initiated by the dissociation of the
      hemoprotein from its binding to cardiolipin, which anchors it to the inner
      mitochondrial membrane. Oxidation of cardiolipin reduces cytochrome c binding and
      results in an increased level of "free" cytochrome c in the intermembrane space.
      Conversely, mitochondrial antioxidant enzymes protect from apoptosis. Hence,
      there is accumulating evidence supporting a direct link between mitochondria,
      oxidative stress and cell death.

PMID- 17453161
TI  - Dynamics of lipid raft components during lymphocyte apoptosis: the paradigmatic
      role of GD3.
AB  - Several investigations have been carried out since many years in order to
      precisely address the function of lipid rafts in cell life and death. On the
      basis of the biochemical nature of lipid rafts, composed by sphingolipids,
      including gangliosides, sphingomyelin, cholesterol and signaling proteins, a
      plethora of possible interactions with various subcellular structures has been
      suggested. Their structural and functional role at the plasma membrane as well as
      in cell organelles such as endoplasmic reticulum and Golgi apparatus has been
      analyzed in detail in several studies. In particular, a specific activity of
      lipid rafts has been hypothesized to contribute to cell death by apoptosis.
      Although detected in various cell types, the role of lipid rafts in apoptosis has
      however been mostly studied in lymphocytes where the physiological apoptotic
      program occurs after CD95/Fas triggering. In this review, the possible
      contribution of lipid rafts to the cascade of events leading to T cell apoptosis
      after CD95/Fas ligation are summarized. Particular attention has been given to
      the mitochondrial raft-like microdomains, which may represent preferential sites
      where some key reactions can take place and can be catalyzed, leading to either
      survival or death of T cells.

PMID- 17453159
TI  - Embedded together: the life and death consequences of interaction of the Bcl-2
      family with membranes.
AB  - Permeabilization of the outer mitochondrial membrane is the point of no return in
      most programmed cell deaths. This critical step is mainly regulated by the
      various protein-protein and protein-membrane interactions of the Bcl-2 family
      proteins. The two main models for regulation of mitochondrial outer membrane
      permeabilization, direct activation and displacement do not account for all of
      the experimental data and both largely neglect the importance of the membrane. We
      propose the embedding together model to emphasize the critical importance of Bcl
      2 family protein interactions with and within membranes. The embedding together
      model proposes that both pro- and anti-apoptotic Bcl-2 family proteins engage in
      similar dynamic interactions that are governed by membrane dependent
      conformational changes and culminate in either aborted or productive membrane
      permeabilization depending on the final oligomeric state of pro-apoptotic Bax
      and/or Bak.

PMID- 17453162
TI  - HIV protease inhibitors modulate apoptosis signaling in vitro and in vivo.
AB  - HIV protease inhibitors are an integral part of effective anti-HIV therapy. The
      drugs block HIV protease, prevent proper packaging of HIV virions, and decrease
      the HIV viral burden in the peripheral blood of infected individuals. In addition
      to direct anti-viral effects, the HIV protease inhibitors also modulate
      apoptosis. A growing body of work demonstrates the anti-apoptotic effects of HIV
      protease inhibitors on CD4+ and CD8+ T cells during HIV infection. The mechanism
      of this apoptosis inhibition is supported by several proposed hypotheses for how
      they alter the fate of the cell, including preventing adenine nucleotide
      translocator pore function, which consequently prevents loss of mitochondrial
      transmembrane potential. More recently, the anti-apoptotic effects of the HIV
      protease inhibitors have been tested in non-HIV, non-immune cell, whereby
      protease inhibitors prevent apoptosis, and disease in animal models of sepsis,
      hepatitis, pancreatitis and stroke. Interestingly, when HIV protease inhibitors
      are used at supra-therapeutic concentrations, they exert pro-apoptotic effects.
      This has been demonstrated in a number of tumor models. Although it is unclear
      how HIV protease inhibitors can induce apoptosis at increased concentrations,
      future research will define the targets of the immunomodulation and reveal the
      full clinical potential of this intriguing class of drugs.

PMID- 17453163
TI  - Mitochondrial dynamics in the regulation of neuronal cell death.
AB  - Mitochondria undergo continuous fission and fusion events in physiological
      situations. Fragmentation of mitochondria during cell death has been shown to
      play a key role in cell death progression, including release of the mitochondrial
      apoptotic proteins. Ultrastructural changes in mitochondria, such as cristae
      remodeling, is also involved in cell death initiation. Here, we emphasize the
      important role of mitochondrial fission/fusion machinery in neuronal cell death.
      Unlike many other cell types such as immortalized cell lines, neurons are
      distinct morphologically and functionally. We will discuss how this uniqueness
      presents special challenges in the cellular response to neurotoxic stresses, and
      how this affects the mitochondrial dynamics in the regulation of cell death in
      neurons.

PMID- 17453164
TI  - Pathological apoptosis in the developing brain.
AB  - More than half of the initially-formed neurons are deleted in certain brain
      regions during normal development. This process, whereby cells are discretely
      removed without interfering with the further development of remaining cells, is
      called programmed cell death (PCD). The term apoptosis is used to describe
      certain morphological manifestations of PCD. Many of the effectors of this
      developmental cell death program are highly expressed in the developing brain,
      making it more susceptible to accidental activation of the death machinery, e.g.
      following hypoxia-ischemia or irradiation. Recent evidence suggests, however,
      that activation and regulation of cell death mechanisms under pathological
      conditions do not exactly mirror physiological, developmentally regulated PCD. It
      may be argued that the conditions after e.g. ischemia are not even compatible
      with the execution of PCD as we know it. Under pathological conditions cells are
      exposed to various stressors, including energy failure, oxidative stress and
      unbalanced ion fluxes. This results in parallel triggering and potential
      overshooting of several different cell death pathways, which then interact with
      one another and result in complex patterns of biochemical manifestations and
      cellular morphological features. These types of cell death are here called
      "pathological apoptosis," where classical hallmarks of PCD, like pyknosis,
      nuclear condensation and caspase-3 activation, are combined with non-PCD features
      of cell death. Here we review our current knowledge of the mechanisms involved,
      with special focus on the potential for therapeutic intervention tailored to the
      needs of the developing brain.

PMID- 17453165
TI  - The mitochondrial pathway in yeast apoptosis.
AB  - Mitochondria are not only important for the energetic status of the cell, but are
      also the fatal organelles deciding about cellular life and death. Complex
      mitochondrial features decisive for cell death execution in mammals are present
      and functional in yeast: AIF and cytochrome c release to the cytosol,
      mitochondrial fragmentation as well as mitochondrial hyperpolarisation followed
      by an oxidative burst, and breakdown of mitochondrial membrane potential. The
      easy accessibility of mitochondrial manipulations such as repression of
      respiration by growing yeast on glucose or deletion of mitochondrial DNA (rho(0))
      on the one hand and the unique ability of yeast cells to grow on non-fermentable
      carbon sources by switching on mitochondrial respiration on the other hand have
      made yeast an excellent tool to delineate the necessity for mitochondria in cell
      death execution. Yeast research indicates that the connection between
      mitochondria and apoptosis is intricate, as abrogation of mitochondrial function
      can be either deleterious or beneficial for the cell depending on the specific
      context of the death scenario. Surprisingly, mitochondrion dependent yeast
      apoptosis currently helps to understand the aetiology (or the complex biology) of
      lethal cytoskeletal alterations, ageing and neurodegeneration. For example,
      mutation of mitochondrial superoxide dismutase or CDC48/VCP mutations, both
      implicated in several neurodegenerative disorders, are associated with
      mitochondrial impairment and apoptosis in yeast.

PMID- 17453166
TI  - [Bevacizumab (Avastin) related surgical complications: comment to Abbrederis K et
      al. (2007)].

PMID- 17453167
TI  - [Ischemic anastomotic bowel perforation during treatment with bevacizumab 10
      months after surgery].
AB  - BACKGROUND: Bevacizumab (Avastin) is a monoclonal antibody against vascular
      endothelial growth factor (VEGF) receptor that has demonstrated increased overall
      survival when added to standard chemotherapy regimens in patients with metastatic
      colorectal cancer. Gastrointestinal perforation is a known risk factor of unknown
      etiology associated with the use of bevacizumab. OBJECTIVE: We report a 61-year
      old woman with adenocarcinoma of the colon ascendens who underwent hemicolectomy
      and adjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin. Eight
      months after the operation, we started therapy with bevacizumab combined with
      irinotecan, 5-fluorouracil, and leucovorin due to disease progression. Two months
      after completion of this therapy, ischemic anastomotic bowel perforation occurred
      and a resection of the anastomosis was performed. Because of anastomotic
      insufficiency 8 days later, a further revision had to be done and the terminal
      ileum and the colon were brought out through a stoma. DISCUSSION: This case is
      unusual because the time interval between the primary operation and the
      application of bevacizumab is regarded as safe with regard to the risk of
      perforation. An ischemic genesis of the perforation was considered on the basis
      of the histopathological workup. In case of perforations during therapy with
      bevacizumab, a safe surgical approach should be preferred, i.e., a transient
      stoma instead of a primary reconstruction of the bowel passage.

PMID- 17453168
TI  - [Hypocomplementemic urticarial vasculitis syndrome. Successful therapy with
      intravenous immunoglobulins].
AB  - Autoimmune diseases can initially present as chronic urticaria. We describe the
      course of a patient with hypocomplementemic urticarial vasculitis syndrome (HUVS)
      as well as his successful treatment with high-dose intravenous immunoglobulins
      (IVIG). HUVS was diagnosed clinically and confirmed by histology and laboratory
      studies. After only one cycle with IVIG (2 g/kg) all HUVS symptoms were
      significantly decreased.

PMID- 17453169
TI  - EWS/FLI-1 oncoprotein subtypes impose different requirements for transformation
      and metastatic activity in a murine model.
AB  - Ewing sarcoma/primitive neuroectodermal tumors (EWS/PNET) are characterized by
      specific chromosomal translocations most often generating a chimeric EWS/FLI-1
      gene. Depending on the number of juxtaposed exons assembled, several fusion types
      have been described with different incidences and prognoses. To assess the impact
      of each fusion type on the specific phenotypic, tumorigenic, and metastatic
      features of EWS/PNET, we developed an amenable system using a murine mesenchymal
      multipotent C3H10T1/2 cell line. Upon transduction of EWS/FLI-1, cells acquired
      dramatic morphological changes in vitro, including a smaller size and "neurite
      like" membrane elongations. Chimeric fusion proteins conferred oncogenic
      properties in vitro, including anchorage-independent growth and an increased rate
      of proliferation. Furthermore, EWS/FLI-1 expression blocked mineralization, with
      concomitant repression of osteoblastic genes, and induced a dramatic repression
      of the adipocytic differentiation program. Moreover, EWS/FLI-1 promoted an
      aberrant neural phenotype by the de novo expression of specific neural genes. The
      intramuscular injection of transduced cells led to tumor development and the
      induction of overt osteolytic lesions. Analogously, to what was observed in human
      tumors, type 2 EWS/FLI-1 cells formed primary tumors in immunodeficient mice with
      a higher incidence and a lower latency than cells bearing types 1 and 3 fusions.
      By contrast, cells expressing types 2 and 3 fusions showed specific metastatic
      activity with a higher number of macroscopic metastases in soft tissues and
      osteolytic lesions in the limbs as compared to type-1-expressing cells.
      Therefore, the structure of each oncoprotein strongly influenced its
      tumorigenicity and metastagenicity. Thus, this model provides a basis for
      understanding the genetic determinants involved in Ewing tumor development and
      metastatic activity and represents a cellular system to analyze other
      oncoproteins involved in human sarcomagenesis.

PMID- 17453170
TI  - [Prevention of osteoporosis--important for the urologist?].
AB  - Osteoporosis is a systemic disease of the bones with increasing incidence in the
      elderly. Over the age of 50 years bone mineral density continuously decreases
      resulting in osteoporotic fracture. Osteoporosis is positively correlated with
      late-onset hypogonadism and increases under androgen deprivation therapy. The
      evaluation of osteoporosis should be done in cooperation with an endocrinologist.
      Measurement of bone mineral density is recommended before starting androgen
      deprivation therapy. Patients with fracture and/or decreased bone mineral density
      2.5 or more standard deviations below normal peak bone mass of young men should
      be treated. The appropriate treatment is calcium and vitamin D substitution
      combined with oral or i.v. administration of bisphosphonates.

PMID- 17453171
TI  - [Energy ablative therapy of renal tumours].
AB  - Solid renal tumours with a diameter <4 cm may be effectively cured by partial
      nephrectomy but this is associated with a complication rate of 15-20%. In
      addition, these tumours are more frequently diagnosed in the elderly (<70 years)
      and 26% are aggressive G3 and potentially hazardous tumours. Since these tumours
      are frequently unifocal, spherical, peripherally located and easily accessible
      for minimally invasive approaches, energy ablative techniques are attractive less
      invasive therapeutic options. These tumours may be treated by freezing
      (cryoablation) or by heat (radiofrequency ablation, high intensified focused
      ultrasound). Cryoablation seems to be the most reliable technique with a 1.6%
      recurrence rate over 3 years follow-up but only 1.8% complications. Conversely
      skipping renders RFA unreliable in highly vascularised tumours >3 cm with 23%
      vital tumours to be found at histological work-up. Laparoscopic HIFU is still
      experimental. Percutaneous techniques are less effective as compared with
      laparoscopy with recurrence rates ranging between 13-21% (cryoablation) and 14
      18% (RFA). In addition, oncological follow-up relies solely on radiological
      measurements, frequently without histological verification thus making
      percutaneous techniques unpredictable.

PMID- 17453172
TI  - Heterotic patterns in rapeseed (Brassica napus L.): I. Crosses between spring and
      Chinese semi-winter lines.
AB  - Chinese semi-winter rapeseed is genetically diverse from Canadian and European
      spring rapeseed. This study was conducted to evaluate the potential of semi
      winter rapeseed for spring rapeseed hybrid breeding, to assess the genetic
      effects involved, and to estimate the correlation of parental genetic distance
      (GD) with hybrid performance, heterosis, general combining ability (GCA) and
      specific combining ability (SCA) in crosses between spring and semi-winter
      rapeseed lines. Four spring male sterile lines from Germany and Canada as testers
      were crossed with 13 Chinese semi-winter rapeseed lines to develop 52 hybrids,
      which were evaluated together with their parents and commercial hybrids for seed
      yield and oil content in three sets of field trials with 8 environments in Canada
      and Europe. The Chinese parental lines were not adapted to local environmental
      conditions as demonstrated by poor seed yields per se. However, the hybrids
      between the Chinese parents and the adapted spring rapeseed lines exhibited high
      heterosis for seed yield. The average mid-parent heterosis was 15% and ca. 50% of
      the hybrids were superior to the respective hybrid control across three sets of
      field trials. Additive gene effects mainly contributed to hybrid performance
      since the mean squares of GCA were higher as compared to SCA. The correlation
      between parental GD and hybrid performance and heterosis was found to be low
      whereas the correlation between GCA((f + m)) and hybrid performance was high and
      significant in each set of field trials, with an average of r = 0.87 for seed
      yield and r = 0.89 for oil content, indicating that hybrid performance can be
      predicted by GCA((f + m)). These results demonstrate that Chinese semi-winter
      rapeseed germplasm has a great potential to increase seed yield in spring
      rapeseed hybrid breeding programs in Canada and Europe.

PMID- 17453173
TI  - Cell surface structure enhancing uptake of polyvinyl alcohol (PVA) is induced by
      PVA in the PVA-utilizing Sphingopyxis sp. strain 113P3.
AB  - Polyvinyl alcohol (PVA)-utilizing Sphingopyxis sp. 113P3 (re-identified from
      Sphingomonas sp. 113P3) removed almost 0.5% PVA from culture supernatants in 4
      days. Faster degradation of 0.5% PVA was performed by the periplasmic fraction.
      The average molecular size of PVA in the culture supernatant or cell-bound PVA
      was gradually shifted higher, suggesting that lower molecular size molecules are
      degraded faster. Depolymerized products were found in neither the culture
      supernatant nor the cell-bound fraction; however they were recovered from the
      periplasmic fraction. As extracellular or cell-associated PVA oxidase activity
      was almost undetectable in strain 113P3, degradation of PVA must be performed by
      periplasmic PVA dehydrogenase after uptake into the periplasm. Following the
      consumption of PVA, a dent appeared on the cell surface on day 2 and increased in
      size and depth for 4 days and was maintained for 8 days. Ultrastructural change
      on the cell surface was only observed in PVA medium, but not in nutrient broth
      (NB), suggesting that the change is induced by PVA. Fluorescein-4-isothiocyanate
      labeled PVA was bound more to cells grown in PVA than to cells grown in NB. No
      binding was found with PVA-grown cells treated with formaldehyde. Thus, a dent on
      the cell surface seems to be related to the uptake of PVA.

PMID- 17453174
TI  - Isolation of transposon mutants and characterization of genes involved in biofilm
      formation by Pseudomonas fluorescens TC222.
AB  - Biofilm formation mutants are often found to have defective or altered motility.
      The motility phenotype was exploited to identify Pseudomonas fluorescens biofilm
      formation mutants. Fourteen motility mutants were obtained from P. fluorescens
      isolate TC222 and eight stable mutants were studied further. The eight transposon
      insertion mutants showed altered ability to form biofilm compared with the
      parent. Five Tn5-inserted genes from these mutants were cloned and sequenced.
      Genetic analysis showed that two insertions were located in genes affecting
      multiple cell surface characteristics, including lipopolysaccharide (rfbD) and
      polar flagella (fliR). Three genes encoding for a putative Mig-14 family protein
      (epsB), a probable bacteriophage signal peptide protein (bspA) and a soluble
      pyridine nucleotide transhydrogenase (pyrA) were reported for the first time to
      be involved in biofilm formation. Complementation experiments of rfbD and epsB
      genes proved that biofilm formation of the corresponding mutants could be
      restored. Further semi-quantitative reverse transcription-PCR analysis showed
      that both rfbD and epsB can express their transcripts much higher in the
      complemented strains than that in wild-type strains. The transcripts of both
      genes in their mutants could not be detected.

PMID- 17453175
TI  - F15063, a potential antipsychotic with dopamine D(2)/D(3) antagonist, 5-HT(1A)
      agonist and D(4) partial agonist properties: (IV) duration of brain D2-like
      receptor occupancy and antipsychotic-like activity versus plasma concentration in
      mice.
AB  - F15063 (N-[(2,2-dimethyl-2,3-dihydro-benzofuran-7-yloxy)ethyl]-3-(cyclopent-1
      enyl)-benzylamine fumarate salt) is a novel potential antipsychotic with dopamine
      D(2)/D(3) blocking properties and agonist activity at 5-HT(1A) and D(4)
      receptors. The pertinent parameter for pharmacological activity of antipsychotics
      appears to be central D2-like receptor occupancy. However, its duration is not
      necessarily correlated with drug plasma levels, on which clinical dosing regimens
      are often based. Thus, we compared in mice the duration of actions of F15063 and
      haloperidol to (1) inhibit apomorphine-induced climbing and sniffing (behavioural
      measures of D2-like receptor antagonism) and (2) occupy D2-like receptors in vivo
      in the striatum and olfactory tubercles (inhibition of [(3)H]nemonapride
      binding). Finally, we measured plasma levels of F15063. D2-like receptor
      occupancy in the striatum remained elevated at 1, 4 and 8 h postadministration,
      with both F15063 (ID(50): 7.1, 3.6 and 16.5 mg/kg p.o., respectively) and the
      typical antipsychotic, haloperidol (ID(50): 1.4, 0.52 and 0.53 mg/kg p.o.,
      respectively). This was paralleled by a protracted inhibition of apomorphine
      induced climbing (ED(50): 0.9, 2.8 and 3.6 mg/kg p.o., and 0.21, 0.37 and 0.87
      mg/kg p.o., respectively, for F15063 and haloperidol). In contrast, after
      administration of 10 mg/kg p.o. of F15063, its plasma levels decreased rapidly:
      15.2, 2.1 and 0.6 ng/ml, 1, 4 and 8 h after administration, respectively. A
      similar pattern of results was observed when F15063 and haloperidol were
      administered i.p. and s.c., respectively. To summarise, the time-course of D2
      like receptor occupancy and inhibition of apomorphine-climbing (and sniffing)
      behaviours was similarly long lasting with F15063 and haloperidol. In addition,
      the durations of action of F15063 and haloperidol in a behavioural model of
      antipsychotic-like activity were closely correlated to their occupancy of central
      D2-like receptors, and much longer than their presence in plasma.

PMID- 17453176
TI  - Biosensors based on screen-printing technology, and their applications in
      environmental and food analysis.
AB  - This review summarizes scientific research activity on biosensors, especially
      screen-printed, electrode-based biosensors. The basic configurations of
      biosensors based on screen-printing technology are discussed and different
      procedures for immobilization of the biorecognition component are reviewed.
      Theoretical aspects are exemplified by practical environmental and food-analysis
      applications of screen-printed, electrode-based biosensors.

PMID- 17453177
TI  - Microplasma-based atomic emission detectors for gas chromatography.
AB  - This paper is an update on the development of microplasmas as detectors for gas
      chromatography. Direct current (dc), alternating current (ac), and radio
      frequency (rf) microplasmas developed in recent years will be described with
      their significant analytical results, which mostly concern the detection of
      halogens and sulfur. New results will be added which employ a microhollow cathode
      discharge (MHCD) as excitation source. Emphasis will be given to this microplasma
      which has already been implemented as an element-selective detector for emission
      spectrometry and as ionization source for mass spectrometry. The possibility to
      use it as a multielement-selective detector for gas chromatography will be
      presented. A discussion of the published detection limits of all these
      microplasmas is given.

PMID- 17453178
TI  - Optimization of analytical conditions and validation of a fluorescence method for
      the determination of sulfadiazine in milk.
AB  - This paper describes optimization and validation of a method for sulfadiazine
      determination in milk samples based on sulfadiazine derivatization with
      fluorescamine followed by excitation-emission (fluorescence) measurement. For
      both the optimization and the validation, a comparison between zero-order and
      first-order signals has been made, showing the advantages of using first-order
      signals. In the optimization the effects of the temperature of the derivatization
      reaction, the amount of fluorescamine and the derivatization time on the
      instrumental signal (maximum intensity or the net analyte signal) are studied by
      a factorial experimental design, with the optimal values of these factors which
      give the highest signal being 22 degrees C for the reaction temperature, 50
      microl fluorescamine and 20 min of derivatization time. The validation of the
      method under the optimal experimental conditions shows that the analytical method
      is fit-for-purpose, with values of the capability of detection (CCbeta) of 4.3
      microg l(-1) at a sulfadiazine concentration of zero and with probabilities of a
      false positive and a false negative of 5%. Around the permitted limit
      (established for the sulfonamides at 100 microg l(-1)), CCbeta is 112 microg l(
      1). The precision, as the intermediate reproducibility, was established as 1.2
      and 3.3 microg l(-1) around 0 and 100 microg l(-1), respectively. In the
      application to milk samples spiked with sulfadiazine a mean recovery of around
      90% was obtained with a standard deviation of about 8% (14 samples of different
      concentrations).

PMID- 17453179
TI  - CTA in the detection and quantification of vertebral artery pathologies: a
      correlation with color Doppler sonography.
AB  - INTRODUCTION: We evaluated the feasibility of multidetector CT angiography
      (MDCTA) in the examination of vertebral artery (VA) pathologies and correlated
      the results with those of color Doppler sonography (CDS). METHODS: In this
      retrospective cohort analysis, we identified 65 patients with suspected
      cerebrovascular disease, who underwent MDCTA and CDS of the supraaortic vessels
      within a maximum period of 1 month. We evaluated the feasibility and image
      quality of MDCTA in this indication, compared the value of reformatted images and
      axial source images in the grading of stenoses and correlated these results with
      those of CDS. RESULTS: The image quality of the MDCTA examination was classified
      as good in 64 patients (98.5%) and as moderate in 1 patient (1.5%). Axial source
      images and reformatted images agreed perfectly in terms of stenosis detection and
      grading as well as the detection of hypoplastic VAs (kappa = 1). The correlation
      between MDCTA and CDS was moderate (kappa = 0.56) in terms of stenosis detection
      and quantification and poor (kappa = 0.35) in terms of detection of hypoplasia of
      the VA. CONCLUSION: MDCTA is a feasible method for the evaluation of VA
      pathologies providing a good image quality. Image reformatting does not add any
      diagnostic value to the interpretation of axial source images. The correlation
      between MDCTA and CDS is only moderate, reflecting the clinically important
      limitations of CDS in this indication.

PMID- 17453184
TI  - Clinical outcome of ureteroscopic lithotripsy for 2,129 patients with ureteral
      stones.
AB  - The objective of this study was to retrospectively analyze the clinical outcomes
      of ureteroscopic lithotripsy (USL) performed in patients with ureteral stones,
      and to investigate the factors associated with therapeutic outcomes. This study
      included a total of 2,129 patients with ureteral stones who underwent USL between
      December 1985 and March 2006 in a single institution in Japan. In this series,
      ultrasonic lithotripsy was primarily performed, and forceps and/or baskets were
      occasionally used for the removal of stones. Complete removal was defined as
      total clearance 1 day after the initial USL. The initial stone-free rate
      following a single treatment with USL was 73.3%. Of 569 patients diagnosed as
      having fragmentation of residual stones, additional therapy was not performed for
      115 with stones likely to pass spontaneously, while the remaining 454
      subsequently underwent extracorporeal shock wave lithotripsy. Thereafter,
      ureterolithotomy or percutaneous nephrolithotripsy was further added in 14.
      Ureteral perforation occurred in 14 patients, of whom 2 underwent nephrectomy;
      however, there were no other serious complications that could not be managed by
      conservative treatment. Whether ureteral stones were completely removed by an
      initial USL was significantly associated with the history of ureteral stone,
      severity of clinical symptoms, number of stones, localization of stones and
      maximal diameter of stones. Furthermore, multivariate analysis identified the
      severity of clinical symptoms, number of stones, localization of stones and
      maximal diameter of stones as independent predictors for complete removal of
      ureteral stones by the initial USL application. These findings suggest that USL
      could be a safe and effective treatment option for ureteral stones; however,
      other therapeutic strategies should also be considered in patients with currently
      identified risk factors associated with treatment failure following a single USL
      procedure.

PMID- 17453185
TI  - The effects of shock waves on lung tissue in acute period: an in vivo study.
AB  - The acute effects of extracorporeal shock waves on lung morphology were studied
      by light microscopy in 30 New Zealand rabbits. The left kidneys of the ten
      animals were exposed to 2,000 shockwaves at 18 kV under anesthesia (ESWL group).
      Ten rabbits were in the control group; an intramuscular anesthetic agent
      (ketamine) and intravenous contrast media were administered to ten animals in the
      sham group. Localization of the left kidneys was achieved following contrast
      medium injection through an ear vein under fluoroscopic control. The animals were
      killed after the ESWL procedures and the lungs were removed. Edema, emphysema,
      hemorrhage, congestion, inflammation, loss of normal structure, and epithelial
      desquamation were determined and graded between 0 and 3 in all areas of both
      lungs. In order to determine whether proximity has any effect on the
      histopathological changes, left and right lungs were evaluated separately as well
      as upper and lower lobes. We found that ESWL exposed to kidney also affects all
      areas of the lungs in a rabbit model.

PMID- 17453186
TI  - Sonographic appearance of canal of Nuck hydrocele.
AB  - We present a case of a relatively uncommon entity in a 17-year-old girl who
      presented to the emergency department with right inguinal pain and discomfort. On
      sonography, she was thought to have a hydrocele of a patent processus vaginalis,
      although differentials could not be excluded. The hydrocele was subsequently
      confirmed at surgery. Because this is an uncommonly reported condition, a high
      index of suspicion must be maintained in the appropriate clinical setting. We
      present various sonographic appearances and techniques that have been proposed in
      the literature.

PMID- 17453187
TI  - Intracranial vertebral artery dissection with subarachnoid hemorrhage following
      child abuse.
AB  - Child abuse is often suspected based on particular patterns of injury. We report
      a case of intracranial vertebral artery dissection with subarachnoid hemorrhage
      (SAH) in a 3-month-old boy following child abuse. The mechanisms of injury and
      the clinical and imaging findings are discussed. This particular pattern of
      injury has rarely been reported in association with child abuse. We hope to raise
      physician awareness of child abuse when faced with these imaging findings.

PMID- 17453188
TI  - DNA damage and cellular death in oral mucosa cells of children who have undergone
      panoramic dental radiography.
AB  - BACKGROUND: Despite wide use as a diagnostic tool in medical and dental practice,
      radiography can induce cytotoxic effects and genetic damage. OBJECTIVE: To
      evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and
      karyorrhexis) in exfoliated buccal mucosa cells taken from healthy children
      following exposure to radiation during dental radiography. MATERIALS AND METHODS:
      A total of 17 children who had undergone panoramic dental radiography were
      included. RESULTS: We found no statistically significant differences (P > 0.05)
      between micronucleated oral mucosa cells in children before and after exposure to
      radiation. On the other hand, radiation did cause other nuclear alterations
      closely related to cytotoxicity including karyorrhexis, pyknosis and karyolysis.
      CONCLUSION: Taken together, these results indicate that panoramic dental
      radiography might not induce chromosomal damage, but may be cytotoxic. Overall,
      the results reinforce the importance of evaluating the health side effects of
      radiography and contribute to the micronucleus database, which will improve our
      understanding and practice of this methodology in children.

PMID- 17453189
TI  - MRI characterization of the glenohumeral joint in Apert syndrome.
AB  - The features of craniosynostosis, facial dysmorphism, and distal extremity
      syndactyly in Apert syndrome are well known. However, there have been limited
      descriptions of the associated glenohumeral joint findings. We report the
      radiographic and MRI abnormalities of the glenohumeral joints in a 10-month-old
      girl with Apert syndrome. The MRI findings in the girl support the hypothesis
      that the pathogenesis of Apert syndrome is caused by defective cartilage
      segmentation with premature and abnormal ossification of a cartilage bar within a
      joint space. The resultant shoulder joint deformity is related to glenoid
      hypoplasia and growth arrest of the medial aspect of the humeral head.

PMID- 17453190
TI  - High-attenuation mucus plugs on MDCT in a child with cystic fibrosis: potential
      cause and differential diagnosis.
AB  - High-attenuation mucus plugging is a rare finding in both adults and children.
      When it occurs, the field of differential diagnoses is typically quite small and
      includes acute hemorrhage, aspiration of radiodense material, and allergic
      bronchopulmonary aspergillosis (ABPA). The last of these three diagnoses is the
      most difficult to make, although ABPA is more commonly seen in children with
      cystic fibrosis (CF) or asthma. ABPA is radiographically characterized by
      recurrent mucus plugging, atelectasis, and central bronchiectasis. Thus far, high
      attenuation mucus plugs have only been reported in adults. We report a rare case
      of a child with CF who had high-attenuation mucus plugs and atelectasis that
      raised the possibility of ABPA. We discuss the differential diagnoses of this
      finding and the role of multidetector CT in these children.

PMID- 17453191
TI  - Multiple craniofacial giant cell lesions.

PMID- 17453192
TI  - Microbial asymmetric oxidation of 2-butyl-1,3-propanediol.
AB  - Microbial asymmetric oxidation of 2-butyl-1,3-propanediol was investigated for an
      efficient synthesis of S- and R-enantiomers of 2-hydroxymethylhexanoic acid (2
      HMHA). From an intensive survey of the stocked bacterial strains, Acetobacter
      pasteurianus IAM 12073 and Pseudomonas putida IFO 3738 were found to show the
      highest S- and R-2-HMHA-producing activity, respectively. Under optimized
      conditions, A. pasteurianus (351 mg dry cell weight) and P. putida (642 mg dry
      cell weight) cells produced 12.0 g l(-1) S-2-HMHA with 89% enantiomeric excess
      (e.e.) at 24 h of incubation and 5.1 g l(-1) R-2-HMHA with 94% e.e. at 35 h of
      incubation from 2-butyl-1,3-propanediol.

PMID- 17453193
TI  - Enhanced iturin A production by Bacillus subtilis and its effect on suppression
      of the plant pathogen Rhizoctonia solani.
AB  - Enhanced production of the antibiotic iturin A by Bacillus subtilis RB14-CS
      reached 4.4 g L(-1) in SM medium containing soybean meal and maltose, which was
      16-fold and 2.2-fold higher than that in original and modified number 3S media,
      respectively. When various volumes of RB14-CS cultures grown in SM medium were
      applied to pot tests of tomato damping-off caused by Rhizoctonia solani, damping
      off was dose-dependently suppressed by the cultures. Suppression by SM-grown
      cultures was significantly more effective than that by cultures grown in original
      or modified number 3S media. The iturin A concentrations in soil decreased to
      undetectable levels after 17 days of cultivation in pot tests, indicating that
      iturin A has a low persistence in soil.

PMID- 17453194
TI  - Bioreduction of Pt (IV) from aqueous solution using sulphate-reducing bacteria.
AB  - The aims of this study were to investigate the role of sulphate-reducing bacteria
      in facilitating Pt removal from aqueous solutions and to investigate the role of
      a hydrogenase enzyme in Pt reduction in vitro. To avoid precipitation of Pt as Pt
      sulphide, a resting (non-growing) mixed culture was used. A pH-dependent rate of
      Pt removal from aqueous solution was observed, indicating that metal speciation
      was the main factor for its removal from solution. The maximum initial
      concentration of Pt(IV) that the cells can effectively remove from solution was
      50 mg/l, while the maximum capacity was only 4 mg of Pt per gram of resting
      biomass. Transmission electron microscopy and energy dispersive X-ray analyses
      indicated that Pt was being precipitated in the periplasm, a major area of
      hydrogenase activity in the cells. In vitro investigation of Pt reduction with
      hydrogen as the electron donor showed that 49% was removed within 1 h when a
      relatively pure hydrogenase extract was used, 31% was removed with a cell-free
      soluble extract and 70% removed by live cells.

PMID- 17453195
TI  - Molecular and biochemical characterization of Ba-EGA, a cellulase secreted by
      Bacillus sp. AC-1 from Ampullaria crosseans.
AB  - A novel gene (Ba-ega) of Bacillus sp. AC-1, encoding an endoglucanase (Ba-EGA),
      was cloned and expressed in Escherichia coli. Ba-ega, containing a 1,980-bp open
      reading frame (ORF), encoded a protein of 659 amino acids and had a molecular
      mass of 74.87 kDa. Ba-EGA was a modular enzyme composed of a family-9 glycosyl
      hydrolase catalytic module (CM9) and a family-3 carbohydrate-binding module
      (CBM3). To investigate the functions of the CBM3 and CM9, a number of truncated
      derivatives of Ba-EGA were constructed, and all were active. The catalytic module
      (rCM9) alone was less stable at high temperature than the recombinant Ba-EGA (rBa
      EGA). The temperature stability for the complex of rCM9 and rCBM3 was still lower
      than rBa-EGA, but higher than rCM9 alone. These observations indicated the
      existence of a non-covalent interaction between CM9 and CBM3 that might
      strengthen the stability of CM9. However, this interaction is not strong enough
      to mimic the protective effect of the CBM in the wild-type enzyme.

PMID- 17453196
TI  - Comparative analysis of twin-arginine (Tat)-dependent protein secretion of a
      heterologous model protein (GFP) in three different Gram-positive bacteria.
AB  - In contrast to the general protein secretion (Sec) system, the twin-arginine
      translocation (Tat) export pathway allows the translocation of proteins across
      the bacterial plasma membrane in a fully folded conformation. Due to this
      feature, the Tat pathway provides an attractive alternative to the secretory
      production of heterologous proteins via the Sec system. In this study, the
      potential for Tat-dependent heterologous protein secretion was compared in the
      three Gram-positive bacteria Staphylococcus carnosus, Bacillus subtilis, and
      Corynebacterium glutamicum using green fluorescent protein (GFP) as a model
      protein. In all three microorganisms, fusion of a Tat signal peptide to GFP
      resulted in its Tat-dependent translocation across the corresponding cytoplasmic
      membranes. However, striking differences with respect to the final localization
      and folding status of the exported GFP were observed. In S. carnosus, GFP was
      trapped entirely in the cell wall and not released into the supernatant. In B.
      subtilis, GFP was secreted into the supernatant, however, in an inactive form. In
      contrast, C. glutamicum effectively secreted active GFP. Our results clearly
      demonstrate that a comparative evaluation of different Gram-positive host
      microorganisms is a crucial step on the way to an efficient Tat-mediated
      secretory production process for a desired heterologous target protein.

PMID- 17453197
TI  - Fermentation process development for the production of medium-chain-length poly-3
      hyroxyalkanoates.
AB  - This paper presents a review of the existing fermentation processes for the
      production of medium-chain-length poly-3-hydroxyalkanoates (MCL-PHAs). These
      biodegradable polymers are usually produced most efficiently from structurally
      related carbon sources such as alkanes and alkanoic acids. Unlike alkanoic acids,
      alkanes exhibit little toxicity but their low aqueous solubility limits their use
      in high density culture. Alkanoic acids pose little mass transfer difficulty, but
      their toxicity requires that their concentration be well controlled. Using
      presently available technology, large-scale production of MCL-PHA from octane has
      been reported to cost from US $5 to 10 per kilogram, with expenditures almost
      evenly divided between carbon source, fermentation process, and the separation
      process. However, MCL-PHAs, even some with functional groups in their subunits,
      can also be produced from cheaper unrelated carbon sources, such as glucose.
      Metabolic engineering and other approaches should also allow increased PHA
      cellular content to be achieved. These approaches, as well as a better
      understanding of fermentation kinetics, will likely result in increased
      productivity and lower production costs.

PMID- 17453198
TI  - Cell-penetrating peptides and antibodies: a new direction for optimizing
      radioimmunotherapy.

PMID- 17453210
TI  - Primary cardiac lymphoma presenting with right heart mass and bradycardia.

PMID- 17453213
TI  - Arabidopsis rd29A::DREB1A enhances freezing tolerance in transgenic potato.
AB  - The freezing tolerance of 38 independent transgenic potato lines derived from the
      cultivar Desiree was tested in vitro using plantlets. The lines were transgenic
      for the DREB1A gene under control of the rd29A promoter, both of which were
      derived from Arabidopsis thaliana. The level of damage caused by freezing varied
      significantly among the transgenic clones and a non-transgenic control (cv.
      Desiree). Phenotypic evaluation indicated that the variable responses to freezing
      were attributable to genotypic variation, but freezing tolerance was not
      dependent on the number of insertions. Northern blot analysis using a DREB1A cDNA
      probe revealed high levels of DREB1A expression among the transgenic clones
      during the initial cold exposure at 4 degrees C (after 2 h) and in the early
      stages of freezing (-20 degrees C, 1-10 min). Furthermore, a linear correlation
      was detected between the level of expression and the phenotypic response for all
      lines except D138. Thus, in the case of potato, a significant increase in
      freezing tolerance was observed in vitro on a small scale following the
      introduction of rd29A::DREB1A. Additional testing will show whether this strategy
      can be used for tolerance breeding in potato and to increase the freezing
      tolerance of other agriculturally important crops.

PMID- 17453214
TI  - Transgenic Nicotiana benthamiana plants resistant to cucumber green mottle mosaic
      virus based on RNA silencing.
AB  - RNA silencing technology was used to confer resistance to cucumber green mottle
      mosaic virus (CGMMV). Nicotiana benthamiana was transformed with a transgene
      designed to produce an inverted repeat RNA containing CGMMV-coat protein gene
      (CP) sequences, which were separated by an intron sequence, under the control of
      the cauliflower mosaic virus 35S promoter. We attempted to confirm the resistance
      of seven independent transgenic lines; five lines showed resistance to CGMMV
      infection. The systemic spread of virus was prevented after the inoculation of
      CGMMV, and the CP-specific short interfering RNA (siRNA) was detected in
      resistant lines. Thus, the resistance against CGMMV through RNA silencing is
      strong and efficient.

PMID- 17453215
TI  - Rubidium chloride tolerant callus cultures of rice (Oryza sativa L.) accumulate
      more potassium and cross tolerate to other salts.
AB  - Callus cultures from salt tolerant (CSR-10) and susceptible (Swarnadhan)
      varieties of Oryza sativa L. were established in Murashige and Skoog's (MS)
      medium containing lethal concentrations (50 mM) of rubidium chloride (RbCl) as a
      selective agent. While 95-100% cells were viable in callus cultures grown without
      RbCl, viability was 75% in 50 mM RbCl selected cultures. Growth of RbCl selected
      calli in presence of salt was comparable to that of callus grown without it.
      Cells tolerant to RbCl showed more vacuoles and accumulated more K(+) in
      comparison with their corresponding controls. Suspension cultures were
      established and uptake of (86)Rb(+) was measured at 10 and 20 min intervals,
      which revealed a linear relationship between the absorption of K(+) and time.
      Callus cultures (560-day-old) tolerant to 50 mM RbCl regenerated shoots with 35
      40% frequencies in both the varieties, but the same age-old callus grown in the
      medium devoid of RbCl did not show any organogenesis. Callus cultures that are
      tolerant to 50 mM RbCl when exposed to 25 mM LiCl, 50 mM NaCl, 50 mM KCl and 25
      mM CsCl also exhibited cross tolerance in both the varieties. This is the first
      time that a callus line of rice resistant to RbCl was raised and shown to
      accumulate a major cation K(+ )and also an increased influx of it.

PMID- 17453216
TI  - Agrobacterium-mediated transformation of the dwarf pomegranate (Punica granatum
      L. var. nana).
AB  - The dwarf pomegranate (Punica granatum L. var. nana) is a dwarf ornamental plant
      that has the potential to be the model plant of perennial fruit trees because it
      bears fruits within 1 year of seedling. We established an Agrobacterium-mediated
      transformation system for the dwarf pomegranate. Adventitious shoots regenerated
      from leaf segments were inoculated with A. tumefaciens strain EHA105 harboring
      the binary vector pBin19-sgfp, which contains neomycin phosphotransferase (npt
      II) and green fluorescent protein (gfp) gene as a selectable and visual marker,
      respectively. After co-cultivation, the inoculated adventitious shoots were cut
      into small pieces to induce regeneration, and then selected on MS medium
      supplemented with 0.5 muM alpha-naphthaleneacetic acid (NAA), 5 muM N(6)
      benzyladenine (BA), 0.3% gellan gum, 50 mg/l kanamycin, and 10 mg/l meropenem.
      Putative transformed shoots were regenerated after 6-8 months of selection. PCR
      and PCR-Southern blot analysis revealed the integration of the transgene into the
      plant genome. Transformants bloomed and bore fruits within 3 months of being
      potted, and the inheritance of the transgene was confirmed in T(1) generations.
      The advantage of the transformation of dwarf pomegranate was shown to be the high
      transformation rate. The establishment of this transformation system is
      invaluable for investigating fruit-tree-specific phenomena.

PMID- 17453217
TI  - Quantitative evaluation of muscle perfusion with CEUS and with MR.
AB  - Functional imaging might increase the role of imaging in muscular diseases, since
      alterations of muscle morphology alone are not specific for a particular disease.
      Perfusion, i.e., the blood flow per tissue and time unit including capillary
      flow, is an important functional parameter. Pathological changes of skeletal
      muscle perfusion can be found in various clinical conditions, such as
      degenerative or inflammatory myopathies or peripheral arterial occlusive disease.
      This article reviews the theoretical basics of functional radiological techniques
      for assessing skeletal muscle perfusion and focuses on contrast-enhanced
      ultrasound (CEUS) and magnetic resonance imaging (MRI) techniques. Also, the
      applications of microvascular imaging, such as in detection of myositis and for
      discriminating myositis from other myopathies or evaluating peripheral arterial
      occlusive disease, are presented, and possible clinical indications are
      discussed. In conclusion, dedicated MR and CEUS methods are now available that
      visualize and quantify (patho-)physiologic information about microcirculation
      within skeletal muscles in vivo and hence establish a useful diagnostic tool for
      muscular diseases.

PMID- 17453218
TI  - [Unilateral granulomatous keratoconjunctivitis].

PMID- 17453219
TI  - Colonic perforation caused by anorectal manometry.

PMID- 17453220
TI  - Scleroderma -- news to tell.
AB  - Scleroderma is a chronic fibrosing disease, in which an early inflammatory
      reaction precedes the fibrotic response. Systematic analysis of the pathways
      involved in the development of the disease together with information derived from
      novel animal models have helped to better understand the mechanisms that trigger
      and sustain fibrotic reactions.

PMID- 17453221
TI  - Randomized comparison of second trimester pregnancy termination utilizing saline
      moistened or dry misoprostol.
AB  - OBJECTIVE: The aim of this randomized prospective study was to compare efficacy
      and side effects of saline moistened misoprostol with dry misoprostol,
      administered 800 mug intravaginally every 6 h up to a maximum of 3 doses in 24 h
      for second trimester pregnancy termination. MATERIALS AND METHODS: A total of 81
      women seeking termination of second trimester pregnancy (55 fetal death, 17 fetal
      structural anomaly, 5 chromosomal abnormality, 4 other reasons) were randomly
      assigned to one of two treatment groups: (1) intravaginal non-moistened (dry)
      misoprostol in group A (n = 40) or (2) misoprostol moistened with 3 ml of saline
      in group B (n = 41). RESULTS: All of the patients in either group aborted within
      48 h (100% success rate). Delivery was achieved in a median (interquartile range)
      of 13 (40) h with the group A protocol and 12 (36) h with the group B protocol (P
      = 0.652). Delivery with first dose, delivery within 12 h and delivery within 24 h
      were similar (P > 0.05) in group B (34.1, 87.5 and 60%, respectively) and group A
      (25, 82.9, 46.3, respectively). Both treatment regimens were tolerable and with
      similar side effects. CONCLUSION: Misoprostol moistened with saline was not more
      effective than dry misoprostol for second trimester pregnancy termination.

PMID- 17453222
TI  - Clinical significance of isolated mega cisterna magna.
AB  - OBJECTIVE: The prevalence and clinical significance of isolated mega cisterna
      magna in both fetuses and adults is not yet well defined. It is therefore
      difficult to provide reliable parental counseling in cases of a fetal sonographic
      diagnosis of this anomaly. The aim of the present study was to, determine the
      cognitive profile of adults with isolated mega cisterna magna. METHODS: We
      reviewed 19,301 consecutive CT/MRI of the brain. Isolated mega cisterna magna was
      observed in 49 cases. A battery of neuropsychological tests was performed in 18
      adults with this anomaly and in 18 controls who had no brain anomaly on CT/MRI.
      RESULTS: Subjects with isolated mega cisterna magna had a lower performance on
      memory tasks [RAVLT saving score (0.8 +/- 0.2 vs. 1.02 +/- 0.2, P = 0.003)] and
      verbal fluency [phonemic fluency (9.4 +/- 4.5 vs. 13.6 +/- 5.3, P = 0.02),
      semantic fluency (19.8 +/- 5.8 vs. 24.4 +/- 7.5, P = 0.05)]. They did not differ
      from controls in regard to the Raven similarity tests indicating that this brain
      anomaly is not associated with impairment of general cognitive abilities.
      CONCLUSION: Adults with isolated mega cisterna have an overall normal cognitive
      functioning but may score inferior to controls on some parameters of memory and
      verbal fluency. Although application of adult cases to the fetuses is not well
      established, this information might be of value in parental counseling in cases
      of a fetus with this anomaly.

PMID- 17453223
TI  - Sonoembryology by three-dimensional ultrasonography: pictorial essay.
AB  - CONTEXT: Three-dimensional ultrasonography in obstetrics has evolved in the last
      years, and nowadays it is a methodology that greatly helps prenatal diagnosis.
      Through its rendering mode it allows the careful evaluation of fetal face and
      limbs, and in multiplanar mode it allows the assessment of the anatomy through
      the many possible planes. In the first trimester of gestation, three-dimensional
      ultrasonography permits the detailed evaluation of embryonic development. Its
      main advantages over two-dimensional ultrasonography are shorter examination time
      and the possibility of storage of the volumes for later processing and analysis.
      AIM: We present a pictorial essay with normal embryo development in the first
      trimester of pregnancy by three-dimensional ultrasonography, from the fifth to
      ninth week.

PMID- 17453224
TI  - Knowledge and practice of family planning and HIV-prevention behaviour among just
      delivered adolescents in Ecuador: the problem of adolescent pregnancies.
AB  - BACKGROUND: Adolescents constitute a high risk population for the spreading of
      sexually transmitted diseases, among them HIV/AIDS. Knowledge regarding
      reproductive issues among them is a key point in order to establish appropriate
      prevention programs. OBJECTIVE: Obtain information regarding the knowledge and
      practice related to family planning and HIV-prevention behaviour among
      adolescents of low income. METHODS: Adolescents aged 19 or less delivering at the
      Enrique C. Sotomayor Obstetrics and Gynecology Hospital, Guayaquil, Ecuador were
      surveyed in the immediate postpartum period with a structured questionnaire
      designed for the purpose. RESULTS: During the study period, 357 pregnant
      adolescents were surveyed. Mean age was 17.2 +/- 1.4 years, 30.8% were aged 16 or
      less. Demographical and obstetrical history differences were found when comparing
      adolescents in relation to age and educational level. A high rate of mothers had
      unplanned pregnancies (63.3%) or did not know what family planning was (49.6%).
      Despite high knowledge of what a condom or an oral contraceptive was, few had
      used them in the past. The most frequently known family planning methods in this
      series, which was age dependent, were: oral contraceptives (90.2%), condoms
      (84.9%), parenteral (66.7%) and intrauterine devices (63.3%). The majority knew
      what HIV/AIDS infection was, the most important sources of knowledge being:
      television, high school source, and family or relatives. A high rate of
      adolescents had never had an HIV test performed in the past with one prior tested
      adolescent resulting in a positive result. There was a high rate of knowledge
      regarding the most frequent HIV transmission routes: sexual intercourse, contact
      with infected blood and vertical transmission. In this series, although condom
      use was the most known way for HIV protection, only 22.2% answered having
      intercourse protected with this method. CONCLUSION: In this adolescent series,
      older age was related to higher knowledge in family planning methods; in global
      despite finding a relatively high knowledge in family planning and HIV related
      issues, contraception use and HIV protection behaviour was low.

PMID- 17453225
TI  - KTP-532 laser-assisted microvascular anastomosis (experimental animal study).
AB  - Former animal studies on laser-assisted microvascular anastomosis performed with
      CO(2)-, argon-, diode-, Holmium:YAG- and Nd:YAG-lasers had already proven the
      stability of the anastomotic sites. Tissue damage remained minimal along the
      anastomosis, while duration of the surgeries decreased significantly compared to
      that of traditionally implemented microvascular sutures. In addition to this,
      foreign body reaction next to end-to-end anastomosis appeared to be minimal due
      to fewer traditional stitches. This animal study was designed in order to
      investigate the durability and the histological properties of microvascular
      anastomosis assisted by KTP-532 laser. Twenty-one Wistar albino rats were used:
      in nine animals the KTP-laser-assisted microvascular anastomosis was carried out
      on the femoral artery. Those nine animals were divided into three groups and each
      of them consisted of three rats. The animals in these three groups were
      sacrificed 4 h, 1 and 4 weeks following the surgery, respectively. In three
      additional animals laser-assisted microvascular anastomosis was done on the
      abdominal aorta. Conventional microvascular sutures were carried out on femoral
      arteries of further nine animals in the control group. The healing process of the
      femoral arteries is documented with figures of histological slides both in the
      laser-treated and in the conventionally operated group of rats. The KTP-laser
      assisted microvascular anastomosis failed on the abdominal aorta, as strong
      bleedings occurred after the traditional sutures had been taken out. However, the
      coagulative effect of the KTP-laser could still be used. The authors share the
      opinion that the success of the laser-assisted end-to-end microvascular
      anastomosis does not depend on the wavelength of the applied laser, but can be
      affected by both the calibre of the vessel and the intraluminal pressure.

PMID- 17453226
TI  - The role of barium swallow in the management of the globus pharyngeus.
AB  - Globus pharyngeus is a common benign condition with controversial management.
      Patients with globus pharyngeus are usually investigated to exclude the
      possibility of upper aerodiagestive malignancies. There is a great debate about
      the role of barium swallow in the management of this condition. Review of 1,145
      barium swallow repourts of patients presented with globus pharyngeus between 1999
      and 2004 has failed to diagnose any patient with pharyngeal or oesophageal
      cancer. We conclude that barium swallow should not be requested systematically as
      part of management of globus pharyngeus patients. This approach will reduce the
      cost and radiation effect of unnecessary investigations.

PMID- 17453227
TI  - A validation study of nasal spectroscopy: Rhinolux.
AB  - This study is the first to validate the Rhinolux against acoustic rhinometry in
      detecting nasal mucosal swelling when changing body position from sitting to
      supine. The Rhinolux (Rhios GmbH, Germany) is a new device using a light
      absorption technique called nasal spectroscopy and to measure changes in nasal
      blood volume as a sign of nasal mucosal swelling in real time. The relationship
      between the changes in nasal blood volume measured with the Rhinolux and changes
      in nasal mucosal swelling has however, not previously been validated objectively.
      To evaluate this relationship we compared the Rhinolux to acoustic rhinometry
      following the change in body position from sitting to supine. The study
      population consisted of 20 healthy subjects (7 women, 13 men, mean age 34.7 +/-
      9.3 years). The Rhinolux was applied sitting in the upright position followed by
      5 min in the supine position. Acoustic rhinometry was measured sitting in the
      upright position and after 5 min in the supine position. In seven subjects the
      measurements were repeated on three different days to assess the repeatability.
      The mean change from baseline in minimal cross sectional area DeltaMCA measured
      with acoustic rhinometry was -0.12(+/-0.19) cm2 (right + left side), P = 0.013
      but DeltaE (change in light extinction from baseline) measured with the Rhinolux
      was unchanged 0.02(+/-0.18) optical densities (OD), P = 0.56. There was no
      correlation between DeltaE and DeltaMCA r = 0.028, P = 0.9. The mean DeltaE
      result from repeated measurements on different days was 0.05(+/-0.08) OD, P =
      0.09 and the DeltaMCA was -0.1(+/-0.11) cm2, P = 0.02. This study showed that the
      changes in nasal blood volume measured with the Rhinolux did not reflect changes
      in nasal mucosal swelling measured with acoustic rhinometry when changing body
      position from sitting to supine. The results indicate that the utility of the
      Rhinolux in assessing nasal mucosal reactions has to be evaluated further.

PMID- 17453229
TI  - Coronary heart disease mortality and radon exposure in the Newfoundland fluorspar
      miners' cohort, 1950-2001.
AB  - Kreuzer and coworkers recently reported no association between cumulative
      exposure to radiation and death from cardiovascular disease in a cohort of German
      uranium miners. Here, we report on the relationship between cumulative exposure
      to radon progeny and coronary heart disease among Newfoundland fluorspar miners.
      Previous analyses in this cohort found elevated death rates from coronary heart
      disease among those with higher cumulative radon exposure. However, this finding
      was based on a relatively small number of deaths and was not statistically
      significant. Since then, the follow-up of this cohort has been extended by 10
      years until the end of 2001. Among the 2,070 miners in our study, 267 died from
      coronary heart disease. There was no trend evident between cumulative exposure to
      radon and the relative risk of death from coronary heart disease (P = 0.63). This
      finding was unchanged after adjusting for the lifetime smoking status that was
      available for approximately 54% of the cohort. Similarly, the cumulative radon
      exposure was found to be unrelated to deaths of the circulatory system, acute
      myocardial infarction, and cerebrovascular disease. These findings are consistent
      with those recently reported by Kreuzer and colleagues. We share their view that
      uncontrolled confounding for other coronary heart disease risk factors hinders
      the interpretation of the risk estimates.

PMID- 17453230
TI  - Comparative study on the effect of ethnicity on wisdom tooth eruption.
AB  - The current knowledge base for evaluating the influence of ethnic origin on
      wisdom tooth eruption is still inadequate. We therefore analyzed and compared the
      chronology of wisdom tooth eruption in three ethnic populations-German, Japanese,
      and black South African-based on evidence from 2,482 conventional
      orthopantomograms. The investigated German population ranked in the middle in
      terms of the age of wisdom tooth eruption. The black South African population was
      the fastest and the Japanese population the slowest in terms of reaching the
      respective eruption stages. Population-specific reference data should be used
      when evaluating wisdom tooth eruption for the purpose of forensic age estimation.

PMID- 17453231
TI  - Can transplantation of photoreceptor cells restore vision?

PMID- 17453232
TI  - Visual fixation development in children.
AB  - BACKGROUND: The ability to keep steady fixation on a target is one of several
      aspects of good visual function. However, there are few reports on visual
      fixation during childhood in healthy children. METHODS: An infrared eye-tracking
      device (Orbit) was used to analyse binocular fixation behaviour in 135 non
      clinical participants aged 4-15 years. The children wore goggles and their heads
      were restrained using a chin and forehead rest, while binocularly fixating a
      stationary target for 20 s. RESULTS: The density of fixations around the centre
      of gravity increased with increasing age (p < 0.01), and the time of fixation
      without intruding movements increased with increasing age (p = 0.02), while
      intruding saccades decreased with increasing age (p < 0.01). The number of blinks
      and drifts did not differ between 4 and 15 years, and there were no significant
      differences with regard to gender or laterality in any of the investigated
      variables. No nystagmus was observed. CONCLUSION: This study establishes values
      for visual fixation behaviour in a non-clinical population aged 4-15 years, which
      can be used for identifying children with fixation abnormalities.

PMID- 17453233
TI  - The influence of strength-endurance training on the oxygenation of isometrically
      contracted forearm muscles.
AB  - Ice-climbers frequently use the squeezing of rubber rings for increasing their
      isometric strength-endurance in the forearm muscles. The aim of this study was to
      ascertain whether such training influences oxygenation and endurance of forearm
      muscles at higher as well as lower testing intensities. Fourteen healthy young
      ice-climbers were divided and randomized into two groups. Group A performed a
      specific ice-climbing test, an ice-axe-grasping (axe weight 750 g) until fatigue.
      Group B performed 150 N isometric hand-squeezing of dynamometer until fatigue.
      Both groups performed similar training of squeezing a rubber ring at 30% of
      Maximal Voluntary Contraction (MVC) for 6 weeks. The forearm oxygenation was
      assessed by relative saturation of oxygen (RSO(2)), total hemoglobin
      concentration (RTOTHb), the concentration of oxygenated hemoglobin (ROXYHb) and
      concentration of deoxygenated hemoglobin (RDEOXYHb). The results revealed that
      muscle strength-endurance training increased performance of forearm muscles
      during 150 N contraction with an accompanied increase in oxygenation of the
      exercising muscles. In contrast, the same training did not influence the
      performance of forearm muscles during ice-axe-grasping in spite of increased
      oxygenation. Muscle oxygenation during intense isometric contraction is low in
      spite of an increase observed in training. This may be due to oxygenation levels
      that were below the limit where oxygenation may influence the duration of the
      contraction. Increased oxygenation may have occurred due to an increased blood
      flow and perfusion through superficial muscles or layers may not have contributed
      to the generation of the force of the contraction, as would be the case in deeper
      muscle layers.

PMID- 17453234
TI  - Time resolved kinetics of the guinea pig Na-Ca exchanger (NCX1) expressed in
      Xenopus oocytes: voltage and Ca(2+) dependence of pre-steady-state current
      investigated by photolytic Ca (2+)concentration jumps.
AB  - Kinetic properties of the Na-Ca exchanger (guinea pig NCX1) expressed in Xenopus
      oocytes were investigated by patch clamp techniques and photolytic Ca(2+)
      concentration jumps. Current measured in oocyte membranes expressing NCX1 is
      almost indistinguishable from current measured in patches derived from cardiac
      myocytes. In the Ca-Ca exchange mode, a transient inward current is observed,
      whereas in the Na-Ca exchange mode, current either rises to a plateau, or at
      higher Ca(2+) concentration jumps, an initial transient is followed by a plateau.
      No comparable current was observed in membrane patches not expressing NCX1,
      indicating that photolytic Ca(2+) concentrations jumps activate Na-Ca exchange
      current. Electrical currents generated by NCX1 expressed in Xenopus oocytes are
      about four times larger than those obtained from cardiac myocyte membranes
      enabling current recording with smaller concentration jumps and/or higher time
      resolution. The apparent affinity for Ca(2+) of nonstationary exchange currents
      (0.1 mM) is much lower than that of stationary currents (6 muM). Measurement of
      the Ca(2+) dependence of the rising phase provides direct evidence that the
      association rate constant for Ca(2+) is about 5 x 10(8) M(-1) s(-1) and voltage
      independent. In both transport modes, the transient current decays with a voltage
      independent but Ca(2+)-dependent rate constant, which is about 9,000 s(-1) at
      saturating Ca(2+) concentrations. The voltage independence of this relaxation is
      maintained for Ca(2+) concentrations far below saturation. In the Ca-Ca exchange
      mode, the amount of charge translocated after a concentration jump is independent
      of the magnitude of the jump but voltage dependent, increasing at negative
      voltages. The slope of the charge-voltage relation is independent of the Ca(2+)
      concentration. Major conclusions are: (1) Photolytic Ca(2+) concentration jumps
      generate current related to NCX1. (2) The dissociation constant for Ca(2+) at the
      cytoplasmic transport binding site is about 0.1 mM. (3) The association rate
      constant of Ca(2+) at the cytoplasmic transport sites is high (5 x 10(-8) M(-1)s(
      1)) and voltage independent. (4) The minimal five-state model (voltage
      independent binding reactions, one voltage independent conformational transition
      and one very fast voltage dependent conformational transition) used before to
      describe Ca(2+) translocation at saturating Ca(2+) concentrations is valid for
      Ca(2+) concentrations far below saturation.

PMID- 17453235
TI  - Solid type clear cell carcinoma of the pancreas: differential diagnosis of an
      unusual case and review of the literature.
AB  - Pancreatic neoplasms have been reliably classified on the basis of their
      histopathology and immunophenotype. In this study, we report on a pancreatic
      tumor whose phenotype and genotype could not be assigned to any known tumor
      entity. The tumor was observed in the pancreatic head of a 54-year-old woman. It
      was found to be a solid infiltrating carcinoma with abundant clear cells. Apart
      from cytokeratin, the tumor cells expressed vimentin, S100, and MUC-1. DNA
      microarray analysis revealed a transcription profile clearly differing from that
      of normal pancreatic tissue and pancreatic ductal adenocarcinoma. Despite
      metastatic behavior, the tumor displayed a more favorable course than
      conventional pancreatic ductal adenocarcinoma. We suggest that this tumor be
      called solid type clear cell carcinoma of the pancreas.

PMID- 17453238
TI  - Collagenous gastritis: a case report and review.
AB  - In this article, we report a case of collagenous gastritis in a child and review
      the paediatric cases reported to date. Collagenous gastritis is a rare entity,
      with only less than 30 cases reported so far, including 12 children, since the
      first description of this entity by Colletti and Trainer in 1989. This is a
      histological diagnosis characterised by a dramatically thickened subepithelial
      collagen band in the gastric mucosa associated with an inflammatory infiltrate.
      Children with this condition often present with epigastric pain and severe
      anaemia, with no evidence of extragastric involvement, in contrast to the adult
      patients, where chronic watery diarrhoea is the main presentation due to
      associated collagenous colitis. A macroscopic pattern of gastritis with
      nodularity of gastric mucosa, erythema and erosions are characteristic endoscopic
      findings in paediatric patients. Specific therapy has not been established and
      resolution of the abnormalities, either endoscopic or histological, has not been
      documented. In conclusion, collagenous gastritis is a rare entity of unknown
      aetiology, pathogenesis and prognosis. Gastroenterologists and pathologists need
      to be aware of this condition when evaluating a child with epigastric pain,
      anaemia and upper gastrointestinal bleeding, particularly when endoscopy reveals
      the nodularity of gastric mucosa. The identification, reporting and long-term
      follow-up of cases will shed more light on this puzzling condition.

PMID- 17453237
TI  - Steep increase of incidence of childhood diabetes since 1999 in Austria. Time
      trend analysis 1979-2005. A nationwide study.
AB  - In a prospective population-based incidence study all newly diagnosed type 1
      diabetic patients 0-<15 years of age were registered by the Austrian Diabetes
      Incidence Study Group. The nationwide incidence of type 1 diabetes between 2000
      2005 was compared with the previously published incidence rates. Long-term trends
      as well as seasonal trends were estimated by Poisson regression models. A total
      of 3,599 incident cases (1,908 boys; 1,691 girls) were identified. Case
      ascertainment was >92%. The overall incidence rate doubled from 7.3 (95% CI; 6.8
      7.9)/100,000 in the period 1979-84 to 14.6 (95% CI, 13.7-15.4)/100,000 in the
      time period 2000-2005. A significant increase during the observation period of 26
      years could be demonstrated in all age groups and both sexes (p<0.01), with the
      steepest increment during the last 5 years. Until 1994 the incidence rate in
      children 0-<5 years was rather stable, but afterwards increased dramatically with
      9.2% (95% CI, 5.2-13.4) annually. Despite this steep increase in time trend, we
      did not observe a seasonal variation in this age group (0-<5) in contrast to
      significant seasonal variations in the groups 5-<10 and 10-<15 years of age. Over
      the past 26 years incidence of type 1 diabetes in childhood increased clearly in
      Austria. The steepest rise was observed in the last 5 years and in the younger
      age groups.

PMID- 17453239
TI  - Primary intestinal lymphangiectasia diagnosed by endoscopy following the intake
      of a high-fat meal.

PMID- 17453240
TI  - Therapeutic strategy of untreated de novo acute myeloid leukemia in the elderly:
      the efficacy of continuous drip infusion with low dose cytarabine and etoposide.
AB  - PURPOSE: To evaluate the efficacy and safety of a novel low dose chemotherapy as
      a remission induction regimen for elderly de novo AML patients ineligible for
      intensive chemotherapy. METHOD: Fifty consecutive patients, aged 60 to 85, with
      untreated de novo AML were enrolled. Patients with poor PS or defined non
      hematological complications were given continuous drip infusion of low dose
      cytarabine (Ara-C), 20 mg/body and etoposide (VP-16), 50 mg/body for 10 days (AV
      group). Patients without those comorbidities were given intensive induction
      therapy (S group). After achieving complete remission (CR), S group patients and
      those with improved PS in AV group received consolidation chemotherapy with
      intensive regimen (S-S or AV-S group), and other patients received AV regimen
      repeatedly (AV-AV group). RESULTS: Eighteen (64%; 95% confidence interval (CI),
      0.47-0.82) of 28 patients in AV group and 16 (73%; 95% CI, 0.54-0.91) of 22
      patients in S group achieved CR, respectively. The 1-year OS rates of the
      patients in the AV-AV group (n = 9), AV-S group (n = 9), and S-S group (n = 16)
      were 22, 81, and 78%, respectively. Although the sample size was small, no
      significant difference was observed for the 1-year OS rate between the AV-S and S
      S groups. Regimen related death were 4 patients in S group, while no patient in
      AV group. CONCLUSION: Therapeutic strategy consisting of remission induction
      using AV regimen and consolidation using intensive regimen after improving PS is
      beneficial in the management of elderly AML patients who have difficulty in
      tolerating for intensive induction chemotherapy.

PMID- 17453241
TI  - The association between breastfeeding and breast cancer occurrence among Israeli
      Jewish women: a case control study.
AB  - PURPOSE: Breast cancer remains the major malignant disease among Israeli women,
      with about 4,000 new cases diagnosed annually, and a steadily increasing
      incidence rates. Early in this century investigators noted that nulliparity and a
      history of never having breastfed were more common in women with breast cancer
      than without the disease. Epidemiological evidence on those issues remains
      controversial. The purpose of this study was to clarify those controversial.
      METHODS: A hospital-based case control study was carried out at Nahariya hospital
      (North of Israel) to assess the risk of breast cancer in relation to
      breastfeeding history. A total of 256 recent cases of breast cancer (diagnosed
      between January 1999 and February 2005) and 536 controls were included. Detailed
      information regarding breastfeeding, menstruation, reproductive factors and
      confounders was collected. Adjusted odds ratios and 95% confidence intervals were
      calculated. RESULTS: Short duration of lifetime breastfeeding, late age at first
      breastfeeding and experience of insufficient milk were found to increase breast
      cancer risk. When women who had ever breastfed their infants were compared with
      females who had not, breastfeeding was found to be protective (OR of 0.39; 95% CI
      0.26-0.59). CONCLUSIONS: These findings may have significant impact on
      intervention planning aimed towards breast cancer reduction among Israeli Jewish
      women.

PMID- 17453242
TI  - Control of aggressive fibromatosis by treatment with imatinib mesylate. A case
      report and review of the literature.
AB  - OBJECTIVE: There has been only one report available that focuses on the treatment
      with imatinib mesylate of two individual persons with aggressive fibromatosis.
      The authors concluded that after long-term treatment, for 9 and 11 months, with
      imatinib mesylate, both patients demonstrated radiographic and clinical
      responses. The novel therapy should be considered as salvage in patients with
      aggressive fibromatosis expressed platelet-derived growth factor receptor-alfa,
      beta (PDGFR-alfa, PDGFR-beta), and/or c-kit, whose tumors are uncontrollable by
      the standard management. On the other hand, the number of kinases blocked by
      imatinib mesylate is notching up, for instance the tyrosine kinase, which is
      associated with macrophage-colony stimulating factor receptor (M-CSFR). METHODS:
      The patient was suffering from aggressive fibromatosis after prior therapy
      including surgery (R2), radiotherapy, and systemic treatment with combination of
      tamoxifen and sulindac. The tumor specimen was immunostained for PDGFR-beta and c
      kit (CD117), and PDGFR-alfa and cytokines platelet-derived growth factor-alfa and
      beta were not assessed. The tests for both assessed molecules revealed negative
      results. In spite of this, the patient underwent a unique treatment with imatinib
      mesylate at the dose of 400 mg orally once daily for 3 years and 2 months.
      RESULTS: After three months of the therapy, radiographic (met criteria of SD but
      small decrease of the tumor was noted) and clinical responses were recorded for
      the first time. The same was seen after 6 and 13 months of therapy continuation
      with imatinib mesylate. Currently, the patient is treated with imatinib mesylate
      (400 mg orally once daily) without any toxicity effects. The last MRI revealed
      readily a smaller tumor (35 x 20 mm) after such a therapy lasted more than 3
      years. CONCLUSIONS: Treatment with imatinib mesylate has been a well-accepted
      therapy for chronic myelogenous leukemia (CML) and gastrointestinal stromal
      tumors (GIST). There have been established four kinases (p210(bcr/abl), c-kit,
      PDGFR-alfa, PDGFR-beta) suggested as the target for imatinib mesylate. Other
      potential targets will be discovered as it has lately been determined that M-CSFR
      kinase activity was blocked by imatinib mesylate. The salvage therapy for
      aggressive fibromatosis with imatinib mesylate seems to be an attractive
      opportunity for patients with the advanced disease, whose prior therapy failed.

PMID- 17453243
TI  - A fine functional homology between chitinases from host and parasite is relevant
      for malaria transmissibility.
AB  - High levels of plasma chitotriosidase are a marker of macrophage activation in
      several pathologies and, in particular, in human malaria. Plasmodium falciparum,
      during its maturative cycle in the midgut of the Anopheles mosquito, secretes a
      chitinase to disrupt the peritrophic membrane, a necessary step in the migration
      of the parasite from the midgut to the salivary glands of malaria's vector. The
      cooperation between human chitotriosidase (Chit) and the chitinase from P.
      falciparum in attacking the peritrophic membranes in the Anopheles midgut has
      been recently demonstrated by in vivo experiments. The present study confirms, by
      computational methods, this functional homology. A simple sequence analysis
      method, potentially useful to assess fine textual closeness in families of
      homologous proteins, is reported here and applied to a set of chitinases from
      mammals and plasmodia. This analysis confirms the clustering and the phylogenetic
      relationships obtained with well-known alignment methods, but also shows that the
      sequences of chitinases from malaria hosts and malaria parasites are correlated.
      This correlation, a sign of functional homology, is discussed as a condition for
      the spreading of different forms of malaria. From this perspective, one can get
      insight into the origins of malaria and its genetic or pharmacological control.

PMID- 17453244
TI  - Survival and integration of tissue-engineered corneal stroma in a model of
      corneal ulcer.
AB  - Tissue-engineered replacement of diseased or damaged tissue has become a reality
      for some types of tissue, such as skin and cartilage. Tissue-engineered corneal
      stroma represents a promising concept to overcome the limitations of cornea
      replacement with allograft. In this study, porcine cornea was decellularized by a
      series of extraction methods, and the in vivo biocompatibility of the scaffold
      was measured subcutaneously in rabbits (n = 8). These were not acutely rejected
      and no abscesses were observed by hematoxylin and eosin staining at the 8th week,
      indicating that the scaffolds had good biocompatibility. To investigate the
      potential value of clinical applications, rabbit stromal keratocytes were
      implanted onto decellularized scaffolds to fabricate tissue-engineered corneal
      stroma. Allograft, tissue-engineered corneal stroma, or scaffolds were implanted
      into a model of corneal ulcer. The survival and reconstruction of corneal
      transplantation were morphologically evaluated by light and electron microscopy
      until the 32nd week after implantation. Experiments involving transplantation
      indicated that the epithelial and stromal defect healed quickly, with improvement
      in corneal clarity. The integration of the graft was accompanied by neurite
      ingrowth from the host tissue. By 16 weeks after transplantation, the cornea had
      gradually regained an intact state similar to that of normal cornea. Our results
      demonstrate that the tissue-engineered corneal stroma with allogenetic cells is a
      promising therapeutic method for corneal injury.

PMID- 17453245
TI  - Treatment of diabetic wounds with fetal murine mesenchymal stromal cells enhances
      wound closure.
AB  - Diabetes impairs multiple aspects of the wound-healing response. Delayed wound
      healing continues to be a significant healthcare problem for which effective
      therapies are lacking. We have hypothesized that local delivery of mesenchymal
      stromal cells (MSC) at a wound might correct many of the wound-healing
      impairments seen in diabetic lesions. We treated excisional wounds of genetically
      diabetic (Db-/Db-) mice and heterozygous controls with either MSC, CD45(+) cells,
      or vehicle. At 7 days, treatment with MSC resulted in a decrease in the
      epithelial gap from 3.2 +/- 0.5 mm in vehicle-treated wounds to 1.3 +/- 0.4 mm in
      MSC-treated wounds and an increase in granulation tissue from 0.8 +/- 0.3 mm(2)
      to 2.4 +/- 0.6 mm(2), respectively (mean +/- SD, P < 0.04). MSC-treated wounds
      also displayed a higher density of CD31(+) vessels and exhibited increases in the
      production of mRNA for epidermal growth factor, transforming growth factor beta
      1, vascular endothelial growth factor, and stromal-derived growth factor 1-alpha.
      MSC also demonstrated greater contractile ability than fibroblast controls in a
      collagen gel contraction assay. The effects of locally applied MSC are thus
      sufficient to improve healing in diabetic mice. Possible mechanisms of this
      effect include augmented local growth-factor production, improved
      neovascularization, enhanced cellular recruitment to wounds, and improved wound
      contraction.

PMID- 17453246
TI  - Vagal innervation of intestines: afferent pathways mapped with new en bloc
      horseradish peroxidase adaptation.
AB  - Neural tracers have not typically been employed to determine the pathways
      followed by axons between their perikarya and target tissues. We have adapted the
      tetramethylbenzidine method for horseradish peroxidase (HRP) to stain fibers en
      bloc in organs and thus to delineate axonal trajectories. We have also applied
      this protocol to characterize the pathways that vagal afferents follow to the
      intestines. The protocol confirms that the proximal segment of the duodenum
      receives afferents carried in the vagal hepatic branch and demonstrates that
      vagal afferents innervating the remainder of the small and large intestines
      course through multiple fascicles derived from the celiac branches of the
      abdominal vagus. These fascicles divide, intermingle, and reorganize along the
      abdominal aorta and superior mesenteric artery (SMA), but not along the inferior
      mesenteric artery, and then project to the intestines with secondary arteries
      that branch from the SMA. The inferior pancreaticoduodenal, jejunal, middle
      colic, right colic, and ileocecocolic arteries all carry vagal afferents to
      segments of the intestines. As the arteries derived from the SMA divide
      repeatedly into successively finer branches and course to the intestines, the
      vagal afferent fascicles (typically a pair) running with each arterial branch
      also divide. These divisions generate sets/pairs of finer fascicles coursing with
      even the highest order arterial radicles. The vagal fascicles enter the
      intestinal wall with the vessels and appear to innervate the organ near the point
      of entry. The results verify the practicality and sensitivity of the en bloc HRP
      technique and suggest that the protocol could delineate other peripheral
      pathways.

PMID- 17453247
TI  - Cross-induction of systemic induced resistance between an insect and a fungal
      pathogen in Austrian pine over a fertility gradient.
AB  - Evidence for cross-induction of systemic resistance or susceptibility in plant
      fungus-herbivore interactions is mostly derived from herbaceous model systems and
      not perennial woody plants. Furthermore, the effects of environmental variables
      such as soil fertility on these tripartite interactions are generally unknown.
      This study examined cross-induction of systemic resistance in Pinus nigra
      (Austrian pine) to infection by Sphaeropsis sapinea (a fungal pathogen), or
      feeding by Neodiprion sertifer (European pine sawfly), by prior induction with
      either S. sapinea or N. sertifer, over a fertility gradient. In a replicated 3
      year study, cross-induction of systemic induced resistance (SIR) was found to be
      both asymmetric within a single year and variable between years. Prior induction
      with insect defoliation induced SIR to subsequent fungal challenge in 2006 but
      not in 2005. In 2005, a fertility-independent negative systemic effect of the
      fungal infection on herbivore growth was detected while herbivore survival was
      affected by a significant interaction between induction treatment and fertility
      level in 2006. Prior infection by the fungus induced SIR against the same fungus
      in both years regardless of fertility levels. This is the first report of whole
      plant SIR against a defoliating insect induced by a fungal pathogen and vice
      versa, under variable nutrient availability, in a conifer or any other tree.

PMID- 17453248
TI  - Plasticity in hydraulic architecture of Scots pine across Eurasia.
AB  - Widespread tree species must show physiological and structural plasticity to deal
      with contrasting water balance conditions. To investigate these plasticity
      mechanisms, a meta-analysis of Pinus sylvestris L. sap flow and its response to
      environmental variables was conducted using datasets from across its whole
      geographical range. For each site, a Jarvis-type, multiplicative model was used
      to fit the relationship between sap flow and photosynthetically active radiation,
      vapour pressure deficit (D) and soil moisture deficit (SMD); and a logarithmic
      function was used to characterize the response of stomatal conductance (G(s)) to
      D. The fitted parameters of those models were regressed against climatic
      variables to study the acclimation of Scots pine to dry/warm conditions. The
      absolute value of sap flow and its sensitivity to D and SMD increased with the
      average summer evaporative demand. However, relative sensitivity of G(s) to D
      (m/G (s,ref), where m is the slope and G(s,ref) is reference G(s) at D = 1 kPa)
      did not increase with evaporative demand across populations, and transpiration
      per unit leaf area at a given D increased accordingly in drier/warmer climates.
      This physiological plasticity was linked to the previously reported climate- and
      size-related structural acclimation of leaf to sapwood area ratios. G (s,ref),
      and its absolute sensitivity to D(m), tended to decrease with age/height of the
      trees as previously reported for other pine species. It is unclear why Scots
      pines have higher transpiration rates at drier/warmer sites, at the expense of
      lower water-use efficiency. In any case, our results suggest that these
      structural adjustments may not be enough to prevent lower xylem tensions at the
      driest sites.

PMID- 17453249
TI  - Dietary restriction in two rotifer species: the effect of the length of food
      deprivation on life span and reproduction.
AB  - According to resource allocation theory, animals face a trade off between the
      allocation of resources into reproduction and into individual growth/maintenance.
      This trade off is reinforced when food conditions decline. It is well established
      in biological research that many animals increase their life span when food is in
      suboptimal supply for growth and/or reproduction. Such a situation of reduced
      food availability is called dietary restriction. An increase in life span under
      dietary restricted conditions is seen as a strategy to tolerate periods of food
      shortage so that the animals can start reproduction again when food is in greater
      supply. In this study, the effect of dietary restriction on life span and
      reproduction in two rotifer species, Cephalodella sp. and Elosa worallii, was
      investigated using life table experiments. The food concentration under dietary
      restricted conditions was below the threshold for population growth. It was (1)
      tested whether the rotifers start reproduction again after food replenishment,
      and (2) estimated whether the time scale of dietary restricted conditions is
      relevant for the persistence of a population in the field. Only E. worallii
      responded to dietary restriction with an increase in life span at the expense of
      reproduction. After replenishment of food, E. worallii started to reproduce again
      within 1 day. With an increase in the duration of dietary restricted conditions
      of up to 15 days, which is longer than the median life span of E. worallii under
      food saturation, the life span increased and the life time reproduction
      decreased. These results suggest that in a temporally (or spatially) variable
      environment, some rotifer populations can persist even during long periods of
      severe food deprivation.

PMID- 17453250
TI  - Growing and shrinking in the smallest tortoise, Homopus signatus signatus: the
      importance of rain.
AB  - Climate change models predict that the range of the world's smallest tortoise,
      Homopus signatus signatus, will aridify and contract in the next decades. To
      evaluate the effects of annual variation in rainfall on the growth of H. s.
      signatus, we recorded annual growth rates of wild individuals from spring 2000 to
      spring 2004. Juveniles grew faster than did adults, and females grew faster than
      did males. Growth correlated strongly with the amount of rain that fell during
      the time just before and within the growth periods. Growth rates were lowest in
      2002-2003, when almost no rain fell between September 2002 and August 2003. In
      this period, more than 54% of the tortoises had negative growth rates for their
      straight carapace length (SCL), shell height (SH), and shell volume (SV); maximum
      shrinking for SCL, SH, and SV was 4, 11, and 12%, respectively. The shell of H.
      s. signatus has some flexibility dorso-ventrally, so a reduction in internal
      matter due to starvation or dehydration may have caused SH to shrink. Because the
      length and width of the shell seem more rigid, reversible bone resorption may
      have contributed to shrinkage, particularly of the shell width and plastron
      length. Based on growth rates for all years, female H. s. signatus need 11-12
      years to mature, approximately twice as long as would be expected allometrically
      for such a small species. However, if aridification lowers average growth rates
      to the level of 2002-2003, females would require 30 years to mature.
      Additionally, aridification would lower average and maximum female size,
      resulting in smaller eggs and hatchlings. These projected life history responses
      to aridification heighten the threat posed by the predicted range contraction of
      this red-listed species.

PMID- 17453251
TI  - Plant architecture and meristem dynamics as the mechanisms determining the
      diversity of gall-inducing insects.
AB  - Plant architecture is considered to affect herbivory intensity, but it is one of
      the least studied factors in plant-insect interactions, especially for gall
      inducing insects. This study aimed to investigate the influence of plant
      architecture on the speciose fauna of gall-inducing insects associated with 17
      species of Baccharis. Five architectural variables were evaluated: plant height,
      number of fourth-level shoots, biomass, average level and number of
      ramifications. The number of galling species associated with each host plant
      species was also determined. To test the effects of plant architecture on gall
      richness at the individual level, we used another data set where the number of
      fourth-level shoots and gall richness were determined for B. concinna, B.
      dracunculifolia, and B. ramosissima every 3 weeks during 1 year. The average
      similarity between host species based on gall fauna was low (9%), but plants with
      the same architectural pattern tended to support similar gall communities. The
      most important architectural trait influencing gall richness at the species level
      was the number of fourth-level shoots, which is indicative of the availability of
      plant meristems, a fundamental tissue for gall induction and development. This
      variable also showed a positive correlation with gall richness at the individual
      level. We propose that variations in gall richness among host species are driven
      by interspecific differences in plant architecture via availability of young,
      undifferentiated tissue, which is genetically controlled by the strength of the
      apical dominance. Plant architecture should have evolutionary consequences for
      gall communities, promoting insect radiation among architecturally similar plants
      through host shift and sympatric speciation. We also discuss the role of plant
      architecture in the global biogeography of gall-inducing insects.

PMID- 17453252
TI  - Growth of ectomycorrhizal mycelia and composition of soil microbial communities
      in oak forest soils along a nitrogen deposition gradient.
AB  - Deciduous forests may respond differently from coniferous forests to the
      anthropogenic deposition of nitrogen (N). Since fungi, especially ectomycorrhizal
      (EM) fungi, are known to be negatively affected by N deposition, the effects of N
      deposition on the soil microbial community, total fungal biomass and mycelial
      growth of EM fungi were studied in oak-dominated deciduous forests along a
      nitrogen deposition gradient in southern Sweden. In-growth mesh bags were used to
      estimate the production of mycelia by EM fungi in 19 oak stands in the N
      deposition gradient, and the results were compared with nitrate leaching data
      obtained previously. Soil samples from 154 oak forest sites were analysed
      regarding the content of phospholipid fatty acids (PLFAs). Thirty PLFAs
      associated with microbes were analysed and the PLFA 18:2omega6,9 was used as an
      indicator to estimate the total fungal biomass. Higher N deposition (20 kg N ha(
      1)y(-1) compared with 10 kg N ha(-1)y(-1)) tended to reduce EM mycelial growth.
      The total soil fungal biomass was not affected by N deposition or soil pH, while
      the PLFA 16:1omega5, a biomarker for arbuscular mycorrhizal (AM) fungi, was
      negatively affected by N deposition, but also positively correlated to soil pH.
      Other PLFAs positively affected by soil pH were, e.g., i14:0, a15:0, 16:1omega9,
      a17:0 and 18:1omega7, while some were negatively affected by pH, such as i15:0,
      16:1omega7t, 10Me17:0 and cy19:0. In addition, N deposition had an effect on the
      PLFAs 16:1omega7c and 16:1omega9 (negatively) and cy19:0 (positively). The
      production of EM mycelia is probably more sensitive to N deposition than total
      fungal biomass according to the fungal biomarker PLFA 18:2omega6,9. Low amounts
      of EM mycelia covaried with increased nitrate leaching, suggesting that EM
      mycelia possibly play an important role in forest soil N retention at increased N
      input.

PMID- 17453253
TI  - Effects of fire alone or combined with thinning on tissue nutrient concentrations
      and nutrient resorption in Desmodium nudiflorum.
AB  - This study examined tissue nutrient responses of Desmodium nudiflorum to changes
      in soil total inorganic nitrogen (TIN) and available phosphorus (P) that occurred
      as the result of the application of alternative forest management strategies,
      namely (1) prescribed low-intensity fire (B), (2) overstory thinning followed by
      prescribed fire (T + B), and (3) untreated control C), in two Quercus-dominated
      forests in the State of Ohio, USA. In the fourth growing season after a first
      fire, TIN was significantly greater in the control plots (9.8 mg/kg) than in the
      B (5.5 mg/kg) and T + B (6.4 mg/kg) plots. Similarly, available P was greater in
      the control sites (101 microg/g) than in the B (45 microg/kg) and T + B (65
      microg/kg) sites. Leaf phosphorus ([P]) was higher in the plants from control
      site (1.86 mg/g) than in either the B (1.77 mg/g) or T + B plants (1.73 mg/g).
      Leaf nitrogen ([N]) and root [N] showed significant site-treatment interactive
      effects, while stem [N], stem [P], and root [P] did not differ significantly
      among treatments. During the first growing season after a second fire, leaf [N],
      stem [N], litter [P] and available soil [P] were consistently lower in plots of
      the manipulated treatments than in the unmanaged control plot, whereas the B and
      T + B plots did not differ significantly from each other. N resorption efficiency
      was positively correlated with the initial foliar [N] in the manipulated (B and T
      + B) sites, but there was no such relation in the unmanaged control plots. P
      resorption efficiency was positively correlated with the initial leaf [P] in both
      the control and manipulated plots. Leaf nutrient status was strongly influenced
      by soil nutrient availability shortly after fire, but became more influenced by
      topographic position in the fourth year after fire. Nutrient resorption
      efficiency was independent of soil nutrient availability. These findings enrich
      our understanding of the effects of ecosystem restoration treatments on soil
      nutrient availability, plant nutrient relations, and plant-soil interactions at
      different temporal scales.

PMID- 17453254
TI  - Predator-prey encounter rates in freshwater piscivores: effects of prey density
      and water transparency.
AB  - One of the most fundamental components of predator-prey models is encounter rate,
      modelled as the product of prey density and search efficiency. Encounter rates
      have, however, rarely been measured in empirical studies. In this study, we used
      a video system approach to estimate how encounter rates between piscivorous fish
      that use a sit-and-wait foraging strategy and their prey depend on prey density
      and environmental factors such as turbidity. We first manipulated prey density in
      a controlled pool and field enclosure experiments where environmental factors
      were held constant. In a correlative study of 15 freshwater lakes we then
      estimated encounter rates in natural habitats and related the results to both
      prey fish density and environmental factors. We found the expected positive
      dependence of individual encounter rates on prey density in our pool and
      enclosure experiments, whereas the relation between school encounter rate and
      prey density was less clear. In the field survey, encounter rates did not
      correlate with prey density but instead correlated positively with water
      transparency. Water transparency decreases with increasing prey density along the
      productivity gradient and will reduce prey detection distance and thus predator
      search efficiency. Therefore, visual predator-prey encounter rates do not
      increase, and may even decrease, with increasing productivity despite increasing
      prey densities.

PMID- 17453255
TI  - An analysis of the relative roles of plasticity and natural selection in the
      morphology and performance of a lizard (Urosaurus ornatus).
AB  - Evolutionary ecologists have devoted substantial attention to understanding which
      factors dictate processes of mortality within populations. Our goal was to
      understand the dynamics of natural selection on two performance traits (bite
      force and sprint speed) and associated morphological variables. We first
      quantified performance and morphology for a sample of marked tree lizards
      (Urosaurus ornatus) at the middle of the breeding season. We then sampled the
      same population in the nonbreeding season to determine which of the original
      lizards survived, and we also remeasured morphological and performance variables
      for surviving lizards. We found evidence for directional selection favoring fast
      sprinters in male lizards, but also a nonsignificant stabilizing trend that
      disfavored the very fastest lizards. However, we also detected substantial
      seasonal plasticity in bite force and head width, suggesting that an analysis of
      selection on only preselection (breeding season) values may be overly simplistic.
      Urosaurus males and females with low bite forces (and narrow heads) in the
      breeding season generally increased their bite forces and head widths during the
      nonbreeding season. In contrast, lizards that were initially strong biters in the
      breeding season diminished in head width and declined dramatically in bite force
      (up to about 35%). We suggest that seasonal plasticity could act as a retarding
      force for selection on performance, and could dampen seasonal and year-to-year
      fluctuations in selective pressures. We argue that this phenomenon may be
      particularly likely for performance traits important for social interactions
      related to breeding, such as bite force.

PMID- 17453256
TI  - Physiological and morphological correlates of whole-plant light compensation
      point in temperate deciduous tree seedlings.
AB  - A range of traits, including metabolic costs, biomass allocation and seed
      reserves, may contribute to interspecific variation in the shade tolerance of
      tree seedlings. In addition, shade tolerance may be affected by differential
      responses of species to soil resource availability at low light. We used a custom
      built whole-plant gas-exchange chamber to quantify instantaneous whole-plant
      light compensation point (WPLCP) and to parameterize whole-plant daily C gain
      models for seedlings of eight temperate deciduous tree species. We examined the
      relationship of WPLCP to growth, biomass allocation and gas-exchange under high
      and low light and nutrient availabilities and compared it to WPCLP of naturally
      recruited saplings. For species showing a response, both increased light and
      nutrient availability resulted in increased WPLCP. However, species' responses to
      resource availability did not correspond closely with shade tolerance as has
      generally been predicted. Variation in WPLCP within species was best predicted by
      whole-plant dark respiration rates, leaf-level light compensation point and leaf
      mass per area. Among species, seed size was a strong negative correlate of WPLCP,
      explaining 66% of the variation. Species with the lowest WPLCP maintained lower
      growth rates across treatments but greater biomass in the low-light treatment
      compared with more light-demanding species. These data suggest that a number of
      traits, in particular metabolic costs and seed size, contribute to WPLCP.
      However, gas-exchange-based WPLCP was 1.5-3.5 times lower than corresponding
      growth-based field estimates of WPLCP, suggesting that other factors such as
      biotic interactions or ontogenetic shifts in whole-plant light requirements may
      substantially increase species' WPLCP under natural conditions.

PMID- 17453257
TI  - Production and purification of recombinant human granulocyte-macrophage colony
      stimulating factor (GM-CSF) from high cell density cultures of Pichia pastoris.
AB  - Granulocyte-macrophage colony stimulating factor (GM-CSF) is a hematopoietic
      growth factor, which has been used as a therapeutic agent in clinical cases like
      neutropenia. In this study, we report the production of recombinant human GM-CSF
      in the methylotrophic yeast Pichia pastoris through secretory expression using
      the inducible AOX1 promoter. Recombinant P. pastoris GS115 cells were grown in
      fed batch cultures to obtain a biomass density of 55.6 gDCW L(-1) and a high
      volumetric activity of 131 mg L(-1) of GM-CSF. The protein migrated as a diffuse
      band on SDS-PAGE at the range of 28-35 kDa indicating differential glycosylation.
      The secreted protein was purified to 95% in two steps using cation exchange and
      size exclusion chromatography.

PMID- 17453258
TI  - A single fracture in the ring of vertebrae below the atlas: report of four cases.
AB  - A single fracture of the ring of a vertebra is a rare injury of the spine. In
      this report, we present five single fractures of the posterior ring of the
      cervical spine below the atlas from four patients after motor vehicle accidents.
      Initial radiographs failed to show any of these fractures; all were detected by
      computed tomography. Single ring fractures are stable and none of our patients
      presented with a neurological deficit. Patients were treated conservatively with
      a cervical collar or a cervicothoracic brace. They all recovered without any
      neurological abnormalities.

PMID- 17453259
TI  - Spectrum of biliary abnormalities in hepatic hereditary hemorrhagic
      telangiectasia: demonstration by multidetector computed tomography.
AB  - We present a case in which multidetector computed tomography demonstrated a
      specific pattern of biliary disease associated with hepatic hereditary
      hemorrhagic telangiectasia: multiple intrahepatic stenoses, focal cystic
      dilatations along the course of the intrahepatic ducts, and large biliary cysts
      in conjunction with a normal-appearing extrahepatic bile duct.

PMID- 17453261
TI  - Eligibility for free GP care, "need" and GP visiting in Ireland.
AB  - The determinants of general practitioner (GP) visiting patterns in Ireland, in
      particular the role of eligibility for free GP care, are examined using microdata
      from a nationally representative survey of the population in 2001. Whereas most
      studies find that need factors such as age and health status are most important
      in determining GP visiting rates, the Irish situation is complicated by the
      distinction between medical card patients, who receive free GP visits, and
      private patients, who must pay for each visit. Controlling for a variety of need
      related and other factors, the results show that health status and medical card
      eligibility are consistently most important in explaining differences in GP
      visiting patterns. The medical card result is particularly noteworthy; even when
      differences in age and other observable characteristics between medical card and
      private patients are taken into account, medical card patients are both more
      likely than private patients to visit their GP, and they visit more frequently
      when they do. In addition, we investigated whether individuals just above the
      income threshold for a medical card are disadvantaged in terms of accessing GP
      services in comparison with other private patients on higher incomes. We found
      that there is little significant difference among private patients in GP visiting
      rates as we move up the income distribution.

PMID- 17453260
TI  - Emergency percutaneous treatment of arterial iliac axis ruptures.
AB  - The objective of this paper is to assess the feasibility and effectiveness of
      emergency percutaneous treatment of ruptures of the iliac axis. In 5 years, we
      observed 13 patients (mean age, 62.1 years), 11 with rupture of the external
      iliac artery and two with rupture of the common iliac artery (six traumatic and
      seven iatrogenic). All patients were treated with stent grafts. A follow-up was
      performed with a color Doppler ultrasound at 1, 3, 6, and 12 months during the
      first year and then yearly. Immediate technical success was obtained in all
      cases. During a mean follow-up of 22.3 months, one stent-graft occlusion and one
      infection of a retroperitoneal hematoma occurred. The primary patency rate is
      92.3%. Percutaneous treatment is a feasible and safe tool for iliac axis ruptures
      because it can provide a fast and definitive exclusion of bleeding with a patency
      rate comparable to surgery and less major morbidity and mortality.

PMID- 17453262
TI  - Costing maternal health services in South Tanzania: a case study from Mtwara
      Urban District.
AB  - The following paper presents the methodology and results of a costing exercise of
      maternal health services in Tanzania. The main objective of this study was to
      determine the actual costs of antenatal and obstetric care in different health
      institutions in a district in Tanzania as a basis of more efficient resource
      allocation. A costing tool was developed that allows the calculation of costs of
      service units, such as deliveries and antenatal care, and separates these costs
      from the costs of other services. Time consumed by each activity was used as an
      allocation key. For that purpose, we recorded the personnel consumption with
      different time-study methodologies. This approach was tested and implemented in
      Mtwara Urban District, South Tanzania. The results were analyzed by a spreadsheet
      program. The paper presents average costs for different costing units of maternal
      care. Among other findings, we found that the cost of a normal vaginal delivery
      is US $12.30 in a dispensary and US $6.30 in the hospital--a result that needs
      explanation, as usually one would expect that hospitals are more cost-intensive
      than first-line facilities. However, dispensaries are grossly underutilized so
      that the costs per service unit are rather high. The cost for surgical delivery
      (only in hospitals) was found to be US $69.26 and the average cost per antenatal
      care consultation (only at dispensaries) was US $2.50. We conclude that improved
      planning of elective services is a prerequisite for more effective and efficient
      use of personnel resources. In addition, the definition of medically and
      economically sound standards, in particular staffing standards, is critical to
      make cost analysis an effective management tool to guide rational resource
      allocation.

PMID- 17453263
TI  - Are physician estimates of asthma severity less accurate in black than in white
      patients?
AB  - BACKGROUND: Racial differences in asthma care are not fully explained by
      socioeconomic status, care access, and insurance status. Appropriate care
      requires accurate physician estimates of severity. It is unknown if accuracy of
      physician estimates differs between black and white patients, and how this
      relates to asthma care disparities. OBJECTIVE: We hypothesized that: 1) physician
      underestimation of asthma severity is more frequent among black patients; 2)
      among black patients, physician underestimation of severity is associated with
      poorer quality asthma care. DESIGN, SETTING AND PATIENTS: We conducted a cross
      sectional survey among adult patients with asthma cared for in 15 managed care
      organizations in the United States. We collected physicians' estimates of their
      patients' asthma severity. Physicians' estimates of patients' asthma as being
      less severe than patient-reported symptoms were classified as underestimates of
      severity. MEASUREMENTS: Frequency of underestimation, asthma care, and
      communication. RESULTS: Three thousand four hundred and ninety-four patients
      participated (13% were black). Blacks were significantly more likely than white
      patients to have their asthma severity underestimated (OR = 1.39, 95% CI 1.08
      1.79). Among black patients, underestimation was associated with less use of
      daily inhaled corticosteroids (13% vs 20%, p < .05), less physician instruction
      on management of asthma flare-ups (33% vs 41%, p < .0001), and lower ratings of
      asthma care (p = .01) and physician communication (p = .04). CONCLUSIONS: Biased
      estimates of asthma severity may contribute to racially disparate asthma care.
      Interventions to improve physicians' assessments of asthma severity and patient
      physician communication may minimize racial disparities in asthma care.

PMID- 17453264
TI  - Process of care and outcomes in patients with peripheral arterial disease.
AB  - BACKGROUND: We investigated the association of process of care measures with
      adverse limb and systemic events in patients with peripheral arterial disease
      (PAD). METHODS: We conducted a retrospective cohort study of patients with PAD,
      as defined by an ankle-brachial index (ABI) <0.9. The index date was defined as
      the date, during 1995 to 1998, when the patient was seen in the Michael E.
      DeBakey VA Medical Center noninvasive vascular laboratory and found to have PAD.
      We conducted a chart review for process of care variables starting 3 years before
      the index date and ending at the time of the first event or the final visit
      (December 31, 2001), whichever occurred first. We examined the association
      between PAD process of care measures, including risk factor control, and
      prescribing of medication, with time of the patient's first major limb event or
      death. RESULTS: Of the 796 patients (mean age, 65 +/- 9.9 years), 230 (28.9%
      experienced an adverse limb event (136 lower-extremity bypass, 94 lower-extremity
      amputation), and 354 (44.5%) died. Of the patients who died, 247 died without a
      preceding limb event. Glucose control was protective against death or a limb
      event with a hazard ratio (HR) of 0.74 (95% confidence limits [CL] 0.60, 0.91, P
      = 0.004). African Americans were at 2.8 (95% CL 1.7, 4.5) times the risk of
      Whites or Hispanics for an adverse limb event. However, this risk was no longer
      significant if their glucose was controlled. For process measures, the dispensing
      of PAD specific medication (HR 1.4, 95% CL 1.1, 1.7) was associated an increased
      risk for an adverse outcome. CONCLUSIONS: Our data suggest that glucose control
      is key to reducing the risk for adverse outcomes, particularly limb events in
      African Americans. Certain process of care measures, as markers of disease
      severity and disease management, are associated with poor outcomes in patients
      with PAD. Further work is needed to determine the role of early disease
      intervention to reduce poor outcomes in patients with PAD.

PMID- 17453265
TI  - Cognitive assessment of older primary care patients with and without memory
      complaints.
AB  - BACKGROUND: Dementia screening is currently recommended only for symptomatic
      patients. OBJECTIVE: To evaluate memory complaints, a mental status test, and
      several cognitive tests as dementia screens in primary care. DESIGN: Cross
      sectional clinical epidemiologic study. PARTICIPANTS: Three hundred thirty-nine
      comprehensively assessed, primary care patients aged > or = 65 years.
      MEASUREMENTS: Memory complaints were abstracted from chart review. Scores on Mini
      Mental State Examination (MMSE) and domain-specific cognitive testing were
      compared to a dementia diagnosis based on Clinical Dementia Rating score > or =
      1, and areas under the receiver operating characteristic curves (AUC) were
      calculated. Classification and regression tree analyses were performed on memory
      complaints and tests with the highest AUCs. RESULTS: Of 33 patients with
      dementia, only 5 had documented memory complaints. In 25 patients with documented
      memory complaints, no cognitive tests further improved identification of the 5
      with dementia. In 28 patients with dementia but without memory complaints, an
      MMSE score < 20 identified 8 cases; among those with MMSE scores 20-21, a visual
      memory test identified a further 11 cases. Further cognitive testing could not
      detect 9 dementia cases without memory complaints and with MMSE scores > or = 22.
      CONCLUSIONS: In older primary care patients with memory complaints, cognitive
      screening does not help identify those who require further examination for
      dementia. Most patients with dementia do not report memory complaints. In these
      asymptomatic individuals, general mental status testing, supplemented by a memory
      test when the mental status score is equivocal, will identify lower-scoring
      patients who need dementia assessment. However, high-scoring asymptomatic
      dementia cases will remain undetected.

PMID- 17453272
TI  - Modeling the impacts of farming practices on water quality in the Little Miami
      River Basin.
AB  - Since intensive farming practices are essential to produce enough food for the
      increasing population, farmers have been using more inorganic fertilizers,
      pesticides, and herbicides. Agricultural lands are currently one of the major
      sources of non-point source pollution. However, by changing farming practices in
      terms of tillage and crop rotation, the levels of contamination can be reduced
      and the quality of soil and water resources can be improved. Thus, there is a
      need to investigate the amalgamated hydrologic effects when various tillage and
      crop rotation practices are operated in tandem. In this study, the Soil Water
      Assessment Tool (SWAT) was utilized to evaluate the individual and combined
      impacts of various farming practices on flow, sediment, ammonia, and total
      phosphorus loads in the Little Miami River basin. The model was calibrated and
      validated using the 1990-1994 and 1980-1984 data sets, respectively. The
      simulated results revealed that the SWAT model provided a good simulation
      performance. For those tested farming scenarios, no-tillage (NT) offered more
      environmental benefits than moldboard plowing (MP). Flow, sediment, ammonia, and
      total phosphorus under NT were lower than those under MP. In terms of crop
      rotation, continuous soybean and corn-soybean rotation were able to reduce
      sediment, ammonia, and total phosphorus loads. When the combined effects of
      tillage and crop rotation were examined, it was found that NT with continuous
      soybean or corn-soybean rotation could greatly restrain the loss of sediments and
      nutrients to receiving waters. Since corn-soybean rotation provides higher
      economic revenue, a combination of NT and corn-soybean rotation can be a viable
      system for successful farming.

PMID- 17453266
TI  - Initiation of benzodiazepines in the elderly after hospitalization.
AB  - OBJECTIVE: To estimate the rate of new chronic benzodiazepine use after
      hospitalization in older adults not previously prescribed with benzodiazepines.
      DESIGN: Retrospective cohort study using linked, population-based administrative
      data. SETTING: Ontario, Canada between April 1, 1992 and March 31, 2005.
      PARTICIPANTS: Community-dwelling seniors who had not been prescribed
      benzodiazepine drugs in the year before hospitalization were selected from all
      1.4 million Ontario residents aged 66 years and older. MAIN OUTCOME MEASURES: New
      chronic benzodiazepine users, defined as initiation of benzodiazepines within 7
      days after hospital discharge and an additional claim within 8 days to 6 months.
      We used multivariate logistic regression to examine for the effect of
      hospitalization on the primary outcome after adjusting for confounders. RESULTS:
      There were 405,128 patient hospitalizations included in the cohort.
      Benzodiazepines were prescribed to 12,484 (3.1%) patients within 7 days of being
      discharged from hospital. A total of 6,136 (1.5%) patients were identified as new
      chronic benzodiazepine users. The rate of new chronic benzodiazepine users
      decreased over the study period from 1.8% in the first year to 1.2% in the final
      year (P < .001). Multivariate logistic regression found that women, patients
      admitted to the intensive care unit or nonsurgical wards, those with longer
      hospital stays, higher overall comorbidity, a prior diagnosis of alcoholism, and
      those prescribed more medications had significantly elevated adjusted odds ratios
      for new chronic benzodiazepine users. Older individuals had a lower risk for the
      primary outcome. CONCLUSION: New benzodiazepine prescription after
      hospitalization occurs frequently in older adults and may result in chronic use.
      A systemic effort to address this risky practice should be considered.

PMID- 17453273
TI  - Intelligent databases assist transparent and sound economic valuation of
      ecosystem services.
AB  - Assessment and economic valuation of services provided by ecosystems to humans
      has become a crucial phase in environmental management and policy-making. As
      primary valuation studies are out of the reach of many institutions, secondary
      valuation or benefit transfer, where the results of previous studies are
      transferred to the geographical, environmental, social, and economic context of
      interest, is becoming increasingly common. This has brought to light the
      importance of environmental valuation databases, which provide reliable valuation
      data to inform secondary valuation with enough detail to enable the transfer of
      values across contexts. This paper describes the role of next-generation,
      intelligent databases (IDBs) in assisting the activity of valuation. Such
      databases employ artificial intelligence to inform the transfer of values across
      contexts, enforcing comparability of values and allowing users to generate custom
      valuation portfolios that synthesize previous studies and provide aggregated
      value estimates to use as a base for secondary valuation. After a general
      introduction, we introduce the Ecosystem Services Database, the first IDB for
      environmental valuation to be made available to the public, describe its
      functionalities and the lessons learned from its usage, and outline the remaining
      needs and expected future developments in the field.

PMID- 17453274
TI  - Sound and fury signifying nothing: using geoinformatics to inform resource policy
      in the Gulf of California, Mexico.
AB  - In this issue of Environmental Management, Glenn and others posit that a previous
      study had analytical and interpretive errors in analysis of shrimp fishing in the
      Upper Gulf of California, Mexico. Unfortunately, much of their evidence is too
      indirect and of insufficient scale to address the central question of salinity in
      the Upper Gulf. Also, many of their suppositions did not include direct
      interviews with local officials or a robust understanding of remote sensing
      literature. This response to their rebuttal presents a set of figures and
      analysis demonstrating that the Colorado River flows into a closed evaporative
      basin known as the Laguna Salada and thus cannot flow into the Gulf of
      California. Readers are asked to examine the images and interpret their meaning
      for themselves.

PMID- 17453275
TI  - Mapping locust habitats in the Amudarya River Delta, Uzbekistan with multi
      temporal MODIS imagery.
AB  - Reed beds of Phragmites australis in the River Amudarya delta near the Aral Sea
      constitute permanent breeding areas of the Asian Migratory locust, Locusta
      migratoria migratoria. Every year, thousands of hectares are treated with broad
      spectrum insecticides to prevent locust swarms from damaging crops in adjacent
      areas. To devise efficient locust monitoring and management plans, accurate and
      updated information about the spatial distribution of reeds is necessary. Given
      the vast geographic extent of the delta, traditional, ground survey methods are
      inadequate. Remotely sensed data collected by the MODIS sensor aboard the TERRA
      satellite provide a useful tool to characterize the spatial distribution of
      reeds. Multi-temporal MODIS data, collected at different times of the growing
      season, were used to generate spectral-temporal signatures for reeds and other
      land cover classes. These spectral-temporal signatures were matched with reed
      phenology. MODIS information was digitally classified to generate a land cover
      map with an overall accuracy of 74%. MODIS data captured 87% of the ground
      verified reed locations. Estimates derived from MODIS data indicate that 18% of
      the study area was covered by reeds. However, high commission error resulted from
      misclassification of reeds mixed with shrubs class and shrubs class as reeds.
      This could have resulted in overprediction of the area covered by reeds.
      Additional research is needed to minimize the overlap between reeds and other
      vegetation classes (shrubs, and reed and shrub mix). Nevertheless, despite its
      relatively low spatial resolution (250 m), multi-temporal MODIS data were able to
      adequately capture the distribution of reeds. Instead of blanketing the fragile
      wetland ecosystem of the Amudarya delta with chemical anti-locust treatments,
      plant protection specialists can use this information to devise ecologically
      sound pest management plans aimed at reducing the adverse environmental impact in
      the zone of the Aral Sea ecological catastrophe. MODIS methodology to identify
      reed stands can be applicable to the Migratory locust habitats in other
      geographic areas.

PMID- 17453276
TI  - Emerging governance approaches for tourism in the protected areas of china.
AB  - This paper examines the recent evolution in the governance of protected area
      tourism in China. China now sees cooperation in the form of public-private
      partnerships occurring between authorized private tourism enterprises in various
      organizational forms and the public managers from specific portfolio departments
      of governments at different levels. Three types of governance models are visible:
      the Leasing Model, the Non-listed Share-holding Model, and the Public-listed
      Share-holding Model. Theories of corporate governance were applied to these
      models to analyze the internal and external mechanisms of supervision and
      incentives for both the government agencies and the authorized tourism
      enterprises for nature-based tourism operations. The Principal-Agent problem and
      the supervision mechanism are the focus of the analysis. The emerging governance
      approaches for tourism in protected areas of China are all theoretically viable,
      as explained by the theory of property rights and corporate governance, and
      practically viable as elaborated in the cases of the three types of governance
      models summarized in this paper.

PMID- 17453277
TI  - Early vegetation development on an exposed reservoir: implications for dam
      removal.
AB  - The 4-year drawdown of Horsetooth Reservoir, Colorado, for dam maintenance,
      provides a case study analog of vegetation response on sediment that might be
      exposed from removal of a tall dam. Early vegetation recovery on the exposed
      reservoir bottom was a combination of (1) vegetation colonization on bare, moist
      substrates typical of riparian zones and reservoir sediment of shallow dams and
      (2) a shift in moisture status from mesic to the xeric conditions associated with
      the pre-impoundment upland position of most of the drawdown zone. Plant
      communities changed rapidly during the first four years of exposure, but were
      still substantially different from the background upland plant community.
      Predictions from the recruitment box model about the locations of Populus
      deltoides subsp. monilifera (plains cottonwood) seedlings relative to the water
      surface were qualitatively confirmed with respect to optimum locations. However,
      the extreme vertical range of water surface elevations produced cottonwood seed
      regeneration well outside the predicted limits of drawdown rate and height above
      late summer stage. The establishment and survival of cottonwood at high
      elevations and the differences between the upland plant community and the
      community that had developed after four years of exposure suggest that vegetation
      recovery following tall dam removal will follow a trajectory very different from
      a simple reversal of the response to dam construction, involving not only long
      time scales of establishment and growth of upland vegetation, but also possibly
      decades of persistence of legacy vegetation established during the reservoir to
      upland transition.

PMID- 17453278
TI  - Rice and bricks: environmental issues and mapping of the unusual crop rotation
      pattern in the Kathmandu Valley, Nepal.
AB  - The Kathmandu Valley in Nepal has experienced a very rapid increase in population
      resulting in considerable land use/land cover change and also a series of
      environmental problems. One of the results of the population increase is an
      expansion of brick manufacturing within the Valley because most structures are
      brick. The brick kilns are intense in several locations of the Valley and have an
      interesting pattern of using the same lands for bricks during the dry season and
      then conversion to rice during the wet, summer monsoon months. The increase in
      brick production has contributed to environmental problems including decreased
      soil productivity, lowered ground water levels, and particularly air pollution.
      Brick manufacturing has little, if any, effective regulation. There is a lack of
      current, accurate data on brick production that could be resolved by remote
      sensing methods. Controls should be established and more information acquired on
      the location and impacts of brick production.

PMID- 17453279
TI  - Solar and tidal modulations of fecal indicator bacteria in coastal waters at
      Huntington Beach, California.
AB  - The coastal waters at many beaches in California and the United States are
      afflicted with fecal pollution, which poses a health risk for people exposed to
      the water through recreational activities such as swimming, surfing, and diving.
      Identifying sources of pollution is complicated by oceanographic transport/mixing
      processes and the nonconservative behavior of microorganisms exposed to sunlight
      and hostile marine conditions. This article investigates the variation of fecal
      indicator bacteria (FIB) concentrations in the surf zone and the adjacent coastal
      marsh by applying autocorrelation and cross-correlation analyses that illustrate
      solar and tidal modulations. A steady state bioreactor model was developed to
      explain solar inactivation in the surf zone, whereas a dynamic model was applied
      to explain tidally influenced disturbances in the coastal marsh. These models
      applied to intensive monitoring datasets on FIB and environmental variables have
      provided insights into the biologic and physical processes controlling coastal
      water quality, specifically the influence of sunlight and tides on bacterial
      levels.

PMID- 17453280
TI  - Application of zoning and "limits of acceptable change" to manage snorkelling
      tourism.
AB  - Zoning and applying Limits of Acceptable Change (LAC) are two promising
      strategies for managing tourism in Marine Protected Areas (MPAs). Typically,
      these management strategies require the collection and integration of ecological
      and socioeconomic data. This problem is illustrated by a case study of Koh Chang
      National Marine Park, Thailand. Biophysical surveys assessed coral communities in
      the MPA to derive indices of reef diversity and vulnerability. Social surveys
      assessed visitor perceptions and satisfaction with conditions encountered on
      snorkelling tours. Notably, increased coral mortality caused a significant
      decrease in visitor satisfaction. The two studies were integrated to prescribe
      zoning and "Limits of Acceptable Change" (LAC). As a biophysical indicator, the
      data suggest a LAC value of 0.35 for the coral mortality index. As a social
      indicator, the data suggest that a significant fraction of visitors would find a
      LAC value of under 30 snorkellers per site as acceptable. The draft zoning plan
      prescribed four different types of zones: (I) a Conservation Zone with no access
      apart from monitoring or research; (II) Tourism Zones with high tourism
      intensities at less vulnerable reefs; (III) Ecotourism zones with a social LAC
      standard of <30 snorkellers per site, and (IV) General Use Zones to meet local
      artisanal fishery needs. This study illustrates how ecological and socioeconomic
      field studies in MPAs can be integrated to craft zoning plans addressing multiple
      objectives.

PMID- 17453281
TI  - Ecological feasibility studies in restoration decision making.
AB  - The restoration of degraded systems is essential for maintaining the provision of
      valuable ecosystem services, including the maintenance of aesthetic values.
      However, restoration projects often fail to reach desired goals for a variety of
      ecologic, financial, and social reasons. Feasibility studies that evaluate
      whether a restoration effort should even be attempted can enhance restoration
      success by highlighting potential pitfalls and gaps in knowledge before the
      design phase of a restoration. Feasibility studies also can bring stakeholders
      together before a restoration project is designed to discuss potential
      disagreements. For these reasons, a feasibility study was conducted to evaluate
      the efficacy of restoring a tidal freshwater marsh in the Potomac River near
      Alexandria, Virginia. The study focused on science rather than engineering
      questions, and thus differed in approach from other feasibility studies that are
      mostly engineering driven. The authors report the framework they used to conduct
      a feasibility study to inform other potential restoration projects with similar
      goals. The seven steps of the framework encompass (1) initiation of a feasibility
      study, (2) compilation of existing data, (3) collection of current site
      information, (4) examination of case studies, (5) synthesis of information in a
      handbook, (6) meeting with selected stakeholders, and (7) evaluation of meeting
      outcomes. By conducting a feasibility study using the seven-step framework, the
      authors set the stage for conducting future compliance studies and enhancing the
      chance of a successful restoration.

PMID- 17453282
TI  - Geyser decline and extinction in New Zealand: energy development impacts and
      implications for environmental management.
AB  - Geysers are rare natural phenomena that represent increasingly important
      recreation, economic, and scientific resources. The features of geyser basins,
      including hot springs, mud pots, and fumaroles, are easily damaged by human
      development. In New Zealand, the extinction of more than 100 geysers provides
      important lessons for the environmental management of the world's remaining
      geyser basins. The impacts on New Zealand's geysers are described in sequential
      "phases," including the following: the first use of geothermal resources by the
      indigenous people-the Maori; early European-style tourism and spa development;
      streamside geyser decline caused by river level modification at the Spa geyser
      basin; multiple geyser basin extinctions caused by industrial-scale geothermal
      well withdrawal at Wairakei; the drowning of geysers at Orakeikorako after the
      filling of a hydroelectric reservoir; and geyser decline caused by geothermal
      well heating systems in Rotorua City. The crisis in Rotorua prompted preservation
      of the few remaining geysers at Whakarewarewa -- the last major geyser basin in
      New Zealand. The New Zealand government ordered the geothermal wells within 1.5
      km of Pohutu Geyser, Whakarewarewa, to be closed, which was a locally
      controversial measure. The well closure program resulted in a partial recovery of
      the Rotorua geothermal reservoir, but no extinct geysers recovered. The
      implications of recent geothermal computer modeling and future planning are
      discussed. The New Zealand case suggests that the protection of geysers requires
      strong regulations that prevent incompatible development at the outset, a
      prescription that is especially relevant for the future management of the
      geothermal fields adjacent to the geyser basins of Yellowstone National Park,
      U.S.A.

PMID- 17453283
TI  - Left renal vein graft for vascular reconstruction in abdominal malignancy.
AB  - BACKGROUND: Advanced abdominal malignancies are occasionally invasive for the
      major blood vessels, such as the portal vein (PV), inferior vena cava (IVC), and
      major hepatic veins (HVs), and complete removal of the tumors is required for
      patients undergoing vascular resection and reconstruction. We used left renal
      vein (LRV) grafts for vascular reconstruction in patients with these malignancies
      and evaluated their clinical relevance. METHODS: A total of 113 patients
      underwent vascular resection including the PV (42 patients), IVC (68 patients),
      and HV (3 patients) for hepatobiliary-pancreatic or abdominal tumor resection. Of
      these, 11 patients underwent vascular reconstruction with a LRV graft of the PV,
      superior mesenteric vein (SMV), and HVs in 3 patients each, and the IVC in 2
      patients. The HVs were resected with segmentectomy involving Couinaud's segments
      VII, VIII, and IV; VII, VIII, and II; or III, IV, VIII in each patient. The PV
      and SMV were resected in 5 patients undergoing pancreaticoduodenectomy for
      pancreatic carcinoma, and in 1 patient being treated with extended right
      hepatectomy and pancreaticoduodenectomy for hepatic hilar carcinoma. The IVC was
      partially resected in 1 patient with advanced colon cancer and 1 with malignant
      schwannoma. RESULTS: The mean graft length of LRV obtained was 3.6 (3.5-4.0) cm.
      The graft was used as a tube in 9 patients, and as a patch in 2 patients. The
      mean duration of clamping time was 41.9 (35-60) min. Portal vein thrombosis was
      encountered in 2 patients, and anastomotic stenosis in 1 patient. Other morbidity
      was not related to vascular reconstruction. One patient who underwent extended
      right hepatectomy and pancreaticoduodenectomy died of liver failure in the
      hospital. The serum creatinine level after surgery did not deteriorate except in
      the one patient who died in the hospital. Graft patency was maintained during the
      follow-up period in all patients. CONCLUSIONS: A LRV graft may enhance the
      possibility of vascular reconstruction without deteriorating serum creatinine
      level, and it provides sound graft patency.

PMID- 17453284
TI  - An anterior or posterior approach to partial fundoplication? Long-term results of
      a randomized trial.
AB  - BACKGROUND: Partial fundoplications have been popularized by their lower risk of
      mechanical side effects. The question then emerges whether a similar partial wrap
      should be done posterior or anterior to the distal esophagus? We therefore
      conducted a study to compare the long-term outcome of laparoscopic partial
      fundoplications constructed either as anterior (AF) or posterior (PF) repairs.
      PATIENTS AND METHODS: Ninety-five patients were enrolled in a randomized clinical
      trial. After a mean follow up of 65 months, 43 AF and 45 PF patients remained in
      the study. The levels of reflux control and postfundoplication complaints were
      assessed by use of validated instruments. RESULTS: A posterior fundoplication was
      found to provide significantly better control of reflux related symptoms
      (heartburn p < 0.0001, acid regurgitation p < 0.0001). This was also reflected in
      a significantly lower number of reoperations and need for antisecretory drug
      therapy. The earlier postoperative difference in postfundoplication symptoms had
      disappeared. CONCLUSIONS: A laparoscopic posterior partial fundoplication offers
      a high and durable level of disease control with few side effects. The current
      anterior type of repair cannot be recommended due to insufficient reflux control.

PMID- 17453285
TI  - Surgical resection of hilar cholangiocarcinoma: analysis of survival and
      postoperative complications.
AB  - BACKGROUND: Surgery is the only potentially curative treatment for hilar bile
      duct cancer. This study sought to evaluate the efficacy and feasibility of
      surgical management of hilar bile duct carcinoma, including radical hepatectomy,
      at a single institution. METHODS: We performed a retrospective review of 49
      consecutive patients who underwent surgery at our hospital between 1990 and 2003.
      RESULTS: Altogether, 44 of 49 patients underwent radical hepatectomy combined
      with caudate lobectomy and lymphadenectomy. One and four patients underwent
      partial hepatectomy or bile duct resection, respectively. No patients underwent
      preoperative portal vein embolization. The 5-year survival rate was 39.7%, with a
      median survival time of 3.75 years. The postoperative morbidity and mortality
      rates were 46.8% and 2.0%, respectively. Cox's proportional hazard model revealed
      that lymph node status and the residual tumor factor were independent prognostic
      factors. Multivariate analysis revealed that preoperative hyperbilirubinemia,
      postoperative complications, and extended surgical procedures were independently
      associated with postoperative hyperbilirubinemia. After potentially curative
      resection, 39.4% of patients suffered from disease recurrence. In 60% of the
      total cases, the sites of recurrence were distant metastases. CONCLUSION:
      Surgery, including radical hepatectomy combined with caudate lobectomy and lymph
      node dissection, is a feasible, effective treatment for hilar bile duct cancer.

PMID- 17453287
TI  - Comparison of the sensitivity of physical and virtual laparoscopic surgical
      training simulators to the user's level of experience.

PMID- 17453286
TI  - Genotype-phenotype based surgical concept of hereditary medullary thyroid
      carcinoma.
AB  - BACKGROUND: Since DNA tests have enabled reliable identification of asymptomatic
      RET (rearranged during transfection) gene carriers, myriads of publications have
      appeared on genotype-phenotype relationships. A comprehensive appraisal of this
      body of evidence using evidence-based methodology is pending. METHODS: This study
      was based on systematic evaluation of the literature using evidence-based
      criteria. RESULTS: (1) There is a distinct age-related progression of hereditary
      medullary thyroid carcinoma (MTC) in carriers of RET mutations (grade C). (2)
      Among the high-risk RET mutations, those in codon 634 cause higher penetrance
      rates of the multiple endocrine neoplasia 2A phenotype (MTC, pheochromocytoma,
      and parathyroid hyperplasia/adenoma) than mutations in codons 609, 611, 618, and
      620, irrespective of the amino acid substituting for cysteine (grade C). (3) DNA
      based screening is superior to calcitonin-based screening in asymptomatic RET
      carriers (grade C). (4) Using a worst-case scenario, i.e., considering the
      earliest finding of MTC in asymptomatic RET carriers, pre-emptive thyroidectomy
      should be performed before that time (grade C) to be truly prophylactic.
      Specifically, for carriers of highest-risk mutations (codon 918): within the
      first year of life; for carriers of high-risk mutations (codon 609, 611, 618,
      620, 630, and 634): before the age of 5 years; and for carriers of least-high
      risk mutations (codon 768, 790, 791, 804, and 891): before the age of 5-10 years.
      Strict adherence to these grade C recommendations can result in undertreatment of
      the former (codon 634) and overtreatment of the latter. CONCLUSIONS: These
      genotype-phenotype correlations provide a solid foundation on which to base
      surgical concepts, leaving little room for randomized controlled clinical trials.

PMID- 17453288
TI  - Laparoscopic transhiatal esophagectomy: outcomes.
AB  - BACKGROUND: Laparoscopic transhiatal esophagectomy, indicated for benign and
      malignant esophageal diseases, is a complex operation, often associated with a
      high rate of morbidity and mortality. During the past decade this technique has
      became well accepted among specialized surgeons for the treatment of esophageal
      cancer, avoiding thoracotomy and reducing open access complications. The aim of
      the present study was to retrospectively analyze patients with esophageal cancer
      who underwent laparoscopic transhiatal esophagectomy. METHODS: From November 1993
      to August 2006, 78 patients underwent laparoscopic transhiatal esophagectomy.
      There were 68 cases of esophageal cancer (57 males and 21 females, age range = 28
      73 years) with a predominant rate of squamous cell carcinoma (60.2%). RESULTS:
      The conversion rate was 6.4%. The mean operative time was 153 min with a 12.8%
      rate of cervical leak and a postoperative (30-day) mortality rate of 5.1%. The
      four-year survival rate was 19% as determined within a subgroup of 21 patients
      whose followup during the period was possible. CONCLUSIONS: Laparoscopic
      transhiatal esophagectomy is a safe alternative for experienced professionals.
      This access can improve mortality, hospital stay, and other outcomes when
      compared with open methods.

PMID- 17453289
TI  - Colonoscopic perforations: a review of 30,366 patients.
AB  - BACKGROUND: Although the incidence of perforation after endoscopic procedures of
      the colon is low, the rising number of procedures could pose relevant health
      problems. Recognizing risk factors and optimizing treatment may reduce
      perforation incidence and the probability of (severe) complications. This study
      aimed to determine perforation frequency and the management of endoscopic
      colonoscopic perforation. METHODS: A retrospective review of patient records was
      performed for all patients with iatrogenic colonic perforations after
      sigmoido/colonoscopy between 1990 and 2005. The patients' demographic data,
      endoscopic procedural information, perforation location, therapy, and outcome
      were recorded. RESULTS: In the 16-year period, 30,366 endoscopic colonic
      procedures were performed. In total, 35 colonic perforations occured (0.12%). All
      the patients underwent a laparotomy: for primary repair in 18 cases (56%), for
      resection with anastomosis in 8 cases (25%), and for resection without
      anastomosis in 6 cases (19%). In three patients (8.6%), no perforation was found.
      The postoperative course was uncomplicated in 21 cases (60%) and complicated in
      14 cases (40%), including mortality for 3 patients (8.6% resulting from
      perforations and 0.01% resulting from total endoscopic colon procedures). The
      relative risk ratio of colonoscopic and sigmoidoscopic procedures for
      perforations was 4. Therapeutic procedures show a delay in presentation and
      diagnosis compared with diagnostic procedures. Of the 35 perforations, 26 (74%)
      occurred in the sigmoid colon. CONCLUSION: Iatrogenic colonic perforation is a
      serious but rare complication of colonoscopy. A perforation risk of 0.12% was
      found. The perforation risk was higher for colonoscopic procedures than for
      sigmoidoscopic procedures. The sigmoid colon is the area at greatest risk for
      perforation. Immediate operative management, preferably primary repair and
      sometimes resection, appears to be a good strategy for most patients.

PMID- 17453290
TI  - Establishing a simulation center for surgical skills: what to do and how to do
      it.

PMID- 17453291
TI  - Endoscopic therapy of the buried bumper syndrome: a clinical algorithm.
AB  - BACKGROUND: Buried bumper syndrome is a rare complication of percutaneous
      endoscopic gastrostomy with an overgrowth of the inner flange of the tube.
      Various therapeutic approaches in case studies in the literature are described.
      METHODS: We present the prospective data collection and analysis of 18 cases of
      buried bumper syndrome treated in our institution between 1 January 1998 and 31
      December 2005. RESULTS: The median length of time after the first percutaneous
      endoscopic gastrostomy (PEG) tube insertion was 35 months (range = 1-168 months).
      In 37 endoscopic interventions all ingrown PEG's could be removed or replaced.
      Our experience resulted in a structured clinical treatment algorithm. CONCLUSION:
      In all cases inadequate gastrostomy care must be assumed as the reason for bumper
      overgrowth. Following ESPEN guidelines for PEG care may prevent BBS. BBS can
      routinely be diagnosed and treated by upper gastrointestinal endoscopy in a
      minimally invasive manner.

PMID- 17453292
TI  - Pancreatic cancer epidermal growth factor receptor (EGFR) intron 1 polymorphism
      influences postoperative patient survival and in vitro erlotinib response.
AB  - BACKGROUND: Epidermal growth factor receptor (EGFR) has a highly polymorphic CA
      repeat region that affects transcription efficiency and anti-EGFR drug
      sensitivity in carcinomas. Erlotinib is an EGFR tyrosine kinase inhibitor
      approved for pancreatic cancer treatment. We analyzed the impact of EGFR intron 1
      CA repeat lengths in pancreatic cancer clinical outcome and in vitro response to
      erlotinib. METHODS: Allele-specific EGFR intron 1 lengths were analyzed in 30
      microdissected pancreatic cancer surgical specimens, matched peripheral blood
      samples, and 9 pancreatic cancer cell lines treated with erlotinib. CA repeat
      lengths were correlated with survival, tumor parameters, molecular markers of
      EGFR pathway activation, and in vitro antiproliferative effects of erlotinib.
      RESULTS: Both patient samples and cell lines displayed the full spectrum of EGFR
      CA repeat lengths (14-22 per allele). Patients with shorter sum of total CA
      repeats (<36) had worse median survival than patients with >or=36 repeats (13.7
      vs 30.6 months, P = .002). Shorter patient EGFR intron 1 length correlated with
      EGFR expression (P = .026). Tumor intron 1 length was identical to that of
      matched peripheral blood specimens. There was no correlation between EGFR intron
      1 length and pancreatic cancer stage, nodal status, grade, or expression of p
      EGFR, p-ERK and p-Akt. Shorter EGFR intron 1 length was associated with in vitro
      response to erlotinib treatment (P = .02). CONCLUSIONS: Shorter EGFR intron 1 CA
      repeat length is associated with worse pancreatic cancer clinical prognosis and
      in vitro response to erlotinib. EGFR intron 1 length can be reliably measured in
      peripheral blood and may translate into a quantitative predictive marker of both
      pancreatic cancer aggressiveness and erlotinib sensitivity.

PMID- 17453293
TI  - Patients with locally advanced esophageal carcinoma nonresponder to
      radiochemotherapy: who will benefit from surgery?
AB  - BACKGROUND: In patients who are nonresponders to primary radiochemotherapy (RCT),
      prognosis is poor, leading mostly to palliation. Salvage surgery may have a
      survival benefit otherwise complete. Our aim was to identify predictors of R0
      resection in these patients. METHODS: In 98 nonresponders with locally advanced
      infracarinal tumors, curative salvage surgery was attempted. Resection was R0 in
      62.2% and incomplete in 37.8% of cases. Univariate and multivariate analyses
      included pre-RCT and post-RCT variables collected prospectively. RESULTS: Overall
      survival was higher in the R0 resection group (18.4 vs 8.6 months, P < .001).
      Independent predictors of R0 resection were tumor height <or= 5 cm on barium
      swallow (P = .045) and aortic contact <or= 90 degrees on computed tomography (P =
      .039) evaluated after RCT. Three groups of patients were constructed: 1, tumor
      height <or= 5 cm with aortic contact <or= 90 degrees (n = 43); 2, tumor height
      between 6 and 10 cm with aortic contact <or= 90 degrees (n = 32); and 3, aortic
      contact > 90 degrees , irrespective of tumor height (n = 23). Rates of R0
      resection were 81%, 53%, and 39%, respectively (P = .001). CONCLUSION: Salvage
      esophagectomy should be systematically attempted in nonresponders with tumor
      height <or= 5 cm on barium swallow and aortic contact <or= 90 degrees on computed
      tomography and discussed case by case for other patients.

PMID- 17453294
TI  - Yield and predictors of radiologic studies for identifying distant metastases in
      melanoma patients with a positive sentinel lymph node biopsy.
AB  - BACKGROUND: It is common to obtain radiological studies around the time of a
      positive sentinel lymph node biopsy (SLNB) to exclude patients with distant
      metastases from completion lymph node dissection. The yield of such a work-up is
      unknown. METHODS: Patients were identified from a prospectively maintained
      database. Medical records were reviewed. RESULTS: Over an 8-year period, 181
      patients had a positive SLNB. At least one study (computed tomography or magnetic
      resonance imaging of the brain; chest x-ray; computed tomography of the thorax,
      abdomen, or pelvis; positron-emission tomography scan; or bone scan) was obtained
      around the time of SLNB in 178 patients (98%). Studies were obtained after SLNB
      in 107 patients (59%). Studies ordered after SLNB resulted in indeterminate
      findings in 51 patients (48% of those studied). Among patients tested after SLNB,
      four were found to have metastatic disease (positive rate 3.7%). All of these
      patients had both a thick melanoma and macrometastasis within the SLN. The number
      of patients with indeterminate findings would be decreased and the yield of the
      work-up increased by 4 fold, by restricting the work-up to those with thick
      melanoma and macrometastasis. CONCLUSIONS: Radiological studies obtained after a
      positive SLN produce indeterminate findings in about half of the patients and
      identify distant disease in 3.7%. Restricting work-up to patients with thick
      melanoma and macrometastasis on SLNB would spare patients from indeterminate
      findings and increase the yield of the evaluation.

PMID- 17453295
TI  - The role of growth differentiation factor-9 (GDF-9) and its analog, GDF-9b/BMP
      15, in human breast cancer.
AB  - BACKGROUND: There has been a recent surge of interest in the role of growth
      differentiation factors and other bone morphogenic proteins in the development
      and spread of cancer. In this study we have provided evidence that highlights the
      significance of growth and differentiation factor-9a (GDF-9a) and GDF-9b (bone
      morphogenic protein-15, BMP-15) in breast cancer development and progression.
      METHODS: Primary breast cancer samples (n = 109) and matched background tissues
      from same patients (n = 33) were processed for frozen section and RNA extraction.
      Frozen sections from matched tissues were immunostained with GDF-9a and GDF-9b
      antibodies. Staining intensity was analyzed by computer image analysis. RNA was
      reverse transcribed and quantified before analysis by quantitative polymerase
      chain reaction (Q-PCR). Results were expressed as number of transcripts
      (standardized by beta-actin). The data were compared with the clinical outcome of
      the disease. The biological effects of the molecule were studied using in vitro
      assays after forced expression in breast cancer cells. RESULTS: Highly aggressive
      breast cancer cells did not express GDF-9a. On forced expression of GDF-9a,
      breast cancer cells became less invasive. These laboratory findings were analyzed
      against the clinical information. Primary breast cancer samples with good
      predicted prognosis had a significantly higher level of GDF-9a than in samples
      with poor predicted prognosis (P = .004). Patients who remained disease-free at
      the end of a 10-year follow-up had significantly higher levels of both GDF-9a and
      GDF-9b in their tissue than those with poor clinical outcome (P = .001 and .014,
      respectively). CONCLUSION: Growth differentiation factor-9 family expressed in
      breast cancer has an inhibitory effect on the progression of human breast cancer.

PMID- 17453296
TI  - Pathological and biological differences between screen-detected and interval
      ductal carcinoma in situ of the breast.
AB  - BACKGROUND: The incidence of ductal carcinoma in situ (DCIS) has risen
      dramatically with the introduction of screening mammography. The aim was to
      evaluate differences in pathological and biological characteristics between
      patients with screen-detected and interval DCIS. METHODS: From January 1992 to
      December 2001, 128 consecutive patients had been treated for pure DCIS at our
      institute. From these, 102 had been attending the Dutch breast cancer screening
      program. Sufficient paraffin-embedded tissue was available in 74 out of the 102
      cases to evaluate biological marker expression (Her2/neu, ER, PR, p53 and cyclin
      D1) on tissue microarrays (TMA group). Differences in clinicopathological
      characteristics and marker expression between screen-detected and interval
      patients were evaluated. Screen-detected DCIS was classified as DCIS detected by
      screening mammography, when the two-year earlier examination failed to reveal an
      abnormality. Interval patients were classified as patients with DCIS detected
      within the two-year interval between two subsequent screening rounds. RESULTS:
      Screen-detected DCIS was related with linear branching and coarse granular
      microcalcifications on mammography (p < .001) and with high-grade DCIS according
      to the Van Nuys classification (p = .025). In univariate analysis, screen
      detected DCIS was related with Her2/neu overexpression (odds ratio [OR] = 6.5;
      95%CI 1.3-31.0; p = .020), and interval DCIS was associated with low-grade (Van
      Nuys, OR = 7.3; 95% CI 1.6-33.3; p = .010) and PR positivity (OR = 0.3; 95%CI 0.1
      1.0; p = .042). The multivariate analysis displayed an independent relation of
      Her2/neu overexpression with screen-detected DCIS (OR = 12.8; 95%CI 1.6-104.0; p
      = .018). CONCLUSIONS: These findings suggest that screen-detected DCIS is
      biologically more aggressive than interval DCIS and should not be regarded as
      overdiagnosis.

PMID- 17453297
TI  - Changing perspectives in the assessment of resectability of hilar
      cholangiocarcinoma.

PMID- 17453298
TI  - A randomized phase 2 trial of neoadjuvant chemotherapy in resectable pancreatic
      cancer: gemcitabine alone versus gemcitabine combined with cisplatin.
AB  - BACKGROUND: Survival after surgery for pancreas cancer remains low. This improves
      with adjuvant chemotherapy, but up to 30% patients do not receive the prescribed
      treatment. Neoadjuvant therapy may increase the proportion of patients who
      receive all treatment components, may downstage disease before surgery, and may
      provide early treatment of micrometastases. This randomized phase 2 study
      compares gemcitabine-based chemotherapy regimens to identify the most promising
      regimen for future study. METHODS: Fifty patients with potentially resectable
      pancreas lesions were enrolled onto the study. Twenty-four patients were
      randomized to gemcitabine (1000 mg/m(2)) every 7 days for 43 days; 26 patients
      were randomized to gemcitabine (1000 mg/m(2)) and cisplatin (25 mg/m(2)), 7 to
      the original schedule (omitting day 22) and 19 to a revised schedule due to
      neutropenia (omitting days 15 and 36). The primary outcome measure was resection
      rate. RESULTS: Patients who were allocated to gemcitabine received a median of
      85% of the planned dose. Patients who were allocated to combination treatment
      received a median of 88% and 92% of the planned gemcitabine and cisplatin doses,
      respectively. There were 10 episodes of grade III/IV hematological toxicity in
      each group. Twenty-seven patients (54%) underwent pancreatic resection, 9 (38%)
      in the gemcitabine arm and 18 (70%) in the combination arm, with no increase in
      surgical complications. To date, 34 patients (68%) have died. Twelve-month
      survival for the gemcitabine and combination groups was 42% and 62%. CONCLUSIONS:
      Chemotherapy can be safely administered before pancreatic surgery. Combination
      therapy with gemcitabine and cisplatin is associated with a high resection rate
      and an encouraging survival rate, suggesting that further study is warranted.

PMID- 17453299
TI  - An evolving role of perioperative intraperitoneal chemotherapy after
      cytoreductive surgery for colorectal peritoneal carcinomatosis.

PMID- 17453300
TI  - Efficacy of different technical procedures for sentinel lymph node biopsy in
      gastric cancer staging.
AB  - BACKGROUND: The clinical impact of sentinel lymph node biopsy (SLNB) in gastric
      cancer is controversial. We performed a prospective trial to compare different
      methods: radiocolloid method (RM), dye method (DM), and both methods
      simultaneously (dual method, or DUM) for reliability and therapeutic
      consequences. METHODS: RM and DM were applied in 35 gastric cancer patients.
      After endoscopic peritumoral injection of (99m)Tc-colloid and Patent Blue V, the
      positions of all blue sentinel lymph nodes (SLNs) were recorded, and the SLNs
      microscopically examined by hematoxylin and eosin, step sections, and
      immunohistochemistry. RESULTS: RM, DM, and DUM identified the SLNs in 34 (97%) of
      35 patients. The sensitivity for the prediction of positive lymph node status for
      RM was 22 (92%) of 24, for DM 16 (66%) of 24, and for DUM 22 (92%) of 24. In 7 of
      17 (RM), 5 of 15 (DM), and 7 of 17 (DUM) patients classified as N0 by routine
      hematoxylin and eosin staining, micrometastases or isolated tumor cells were
      found in the SLN (upstaging) after focused examination. If only a limited lymph
      node dissection of the SLN basins would have been performed in patients, residual
      lymph node metastases were left in 9 of 24 (RM), in 7 of 34 (DM), and in 5 of 24
      (DUM) of patients with node-positive disease. CONCLUSIONS: Use of RM was
      superior. DUM did not further increase the sensitivity. A limited lymph node
      dissection-i.e., lymphatic basin in patients with SLN-positive disease-is
      associated with a high risk of residual metastases. Patients with negative SLNs
      may be selected for a limited surgical procedure if they meet certain criteria.

PMID- 17453302
TI  - The origin of two sexes through optimization of recombination entropy against
      time and energy.
AB  - Sexual reproduction in nature requires two sexes, which raises the question why
      the reproductive scheme did not evolve to have three or more sexes. Here we
      construct a constrained optimization model based on the communication theory to
      analyze trade-offs among reproductive schemes with arbitrary number of sexes.
      More sexes on one hand lead to higher reproductive diversity, but on the other
      hand incur greater cost in time and energy for reproductive success. Our model
      shows that the two-sexes reproduction scheme maximizes the recombination entropy
      to-cost ratio, and hence is the optimal solution to the problem.

PMID- 17453303
TI  - Soft tissue modelling of cardiac fibres for use in coupled mechano-electric
      simulations.
AB  - The numerical solution of the coupled system of partial differential and ordinary
      differential equations that model the whole heart in three dimensions is a
      considerable computational challenge. As a consequence, it is not computationally
      practical--either in terms of memory or time--to repeat simulations on a finer
      computational mesh to ensure that convergence of the solution has been attained.
      In an attempt to avoid this problem while retaining mathematical rigour, we
      derive a one dimensional model of a cardiac fibre that takes account of
      elasticity properties in three structurally defined axes within the myocardial
      tissue. This model of a cardiac fibre is then coupled with an
      electrophysiological cell model and a model of cellular electromechanics to allow
      us to simulate the coupling of the electrical and mechanical activity of the
      heart. We demonstrate that currently used numerical methods for coupling
      electrical and mechanical activity do not work in this case, and identify
      appropriate numerical techniques that may be used when solving the governing
      equations. This allows us to perform a series of simulations that: (i)
      investigate the effect of some of the assumptions inherent in other models; and
      (ii) reproduce qualitatively some experimental observations.

PMID- 17453304
TI  - Estimation of dynamic rate parameters in insect populations undergoing sublethal
      exposure to pesticides.
AB  - With newer, more environmentally friendly and, subsequently less lethal,
      pesticides in use, evaluating efficacy of a pesticide now requires more than
      simply counting deaths after treatment. A discrete, age-structured matrix model
      that incorporates a species' life history traits (such as birth rate, death rate
      and fecundity) has previously been used by ecologists. This model will be
      presented and discussed along with an alternative continuous, age-structured
      model which offers significant advantage in considering sublethal damage. We use
      this continuous model to estimate time-dependent mortality parameters in an
      ordinary least-squares technique. Confidence intervals are given and results from
      tests for statistical significance of added parameters are presented.

PMID- 17453306
TI  - Age and sex structured model for assessing the demographic impact of mother-to
      child transmission of HIV/AIDS.
AB  - Age and sex structured HIV/AIDS model with explicit incubation period is proposed
      as a system of delay differential equations. The model consists of two age groups
      that are children (0-14 years) and adults (15-49 years). Thus, the model
      considers both mother-to-child transmission (MTCT) and heterosexual transmission
      of HIV in a community. MTCT can occur prenatally, at labour and delivery or
      postnatally through breastfeeding. In the model, we consider the children age
      group as a one-sex formulation and divide the adult age group into a two-sex
      structure consisting of females and males. The important mathematical features of
      the model are analysed. The disease-free and endemic equilibria are found and
      their stabilities investigated. We use the Lyapunov functional approach to show
      the local stability of the endemic equilibrium. Qualitative analysis of the model
      including positivity and boundedness of solutions, and persistence are also
      presented. The basic reproductive number ([Symbol: see text](0)) for the model
      shows that the adult population is responsible for the spread HIV/AIDS epidemic,
      thus up-to-date developed HIV/AIDS models to assess intervention strategies have
      focused much on heterosexual transmission by the adult population and the
      children population has received little attention. We numerically analyse the
      HIV/AIDS model to assess the community benefits of using antiretroviral drugs in
      reducing MTCT and the effects of breastfeeding in settings with high HIV/AIDS
      prevalence ratio using demographic and epidemiological parameters for Zimbabwe.

PMID- 17453305
TI  - Relative effects of barrier precautions and topical antibiotics on nosocomial
      bacterial transmission: results of multi-compartment models.
AB  - Nosocomial bacterial infections in critically ill patients are generally preceded
      by asymptomatic carriage (i.e. colonization) at one, or even several, body sites
      such as the skin, the gastro-intestinal and the respiratory tract. Different
      routes of transmission between the colonized sites create a complex epidemiology,
      which is additionally complicated by the smallness of the patient population size
      and the rapid patient turnover, characteristic for intensive care units (ICUs).
      Naturally occurring large fluctuations in the prevalence of colonization make it
      very difficult to determine the efficacy of control measures that aim to reduce
      the prevalence of antibiotic-resistant bacteria in ICUs. Theoretical models can
      sharpen our intuition through carefully designed thought experiments. In this
      spirit, we introduce and investigate two models that incorporate the fact that
      patients may be colonized at multiple body sites. Our study can be applied to
      several pathogens commonly found in ICUs, such Pseudomonas Aeruginosa, enteric
      Gram-negative bacteria, MRSA and enterococci. We evaluate the effects of barrier
      precautions (improved hygiene, use of gloves and gowns, etc.) and of
      administration of nonabsorbable antibiotics on the prevalence of colonization in
      ICUs and find that the effect of the controversial, though widely used,
      antibiotic prophylaxis can only be substantial if the patient-to-patient
      transmission has already been reduced to a subcritical level by barrier
      precautions. Taking into account that the very use of antibiotics may increase
      the selection for resistant strains and may thereby only add to the ever
      increasing problem of antibiotic resistance, our findings hence represent a firm
      theoretical argument against the routine use of topical antimicrobial prophylaxis
      for infection control.

PMID- 17453307
TI  - Age-related decline in Kv3.1b expression in the mouse auditory brainstem
      correlates with functional deficits in the medial olivocochlear efferent system.
AB  - Kv3.1b channel protein is widely distributed in the mammalian auditory brainstem,
      but studies have focused mainly on regions critical for temporal processing,
      including the medial nucleus of the trapezoid body (MNTB) and anteroventral
      cochlear nucleus (AVCN). Because temporal processing declines with age, this
      study was undertaken to determine if the expression of Kv3.1b likewise declines,
      and if changes are specific to these nuclei. Immunocytochemistry using an anti
      Kv3.1b antibody was performed, and the relative optical density of cells and
      neuropil was determined from CBA/CaJ mice of four age groups. Declines in
      expression in AVCN, MNTB, and lateral superior olive (35, 26, and 23%) were
      found, but changes were limited to neuropil. Interestingly, cellular optical
      density declines were found in superior paraolivary nucleus, ventral nucleus of
      the trapezoid body, and lateral nucleus of the trapezoid body (24, 29, and 26%),
      which comprise the medial olivocochlear (MOC) feedback system. All declines
      occurred by middle age (15 months old). No age-related changes were found in the
      remaining regions of cochlear nucleus or in the inferior colliculus.
      Contralateral suppression of distortion-product otoacoustic emission amplitudes
      of age-matched littermates also declined by middle age, suggesting a correlation
      between Kv3.1 expression and MOC function. In search of more direct evidence for
      such a correlation, Kv3.1b knockout mice were examined. Knockouts show poor MOC
      function as compared to +/+ and +/- genotypes. Thus, Kv3.1b expression declines
      in MOC neurons by middle age, and these changes appear to correlate with
      functional declines in efferent activity in both middle-aged CBA mice and Kv3.1b
      knockout mice.

PMID- 17453308
TI  - Visually-guided attention enhances target identification in a complex auditory
      scene.
AB  - In auditory scenes containing many similar sound sources, sorting of acoustic
      information into streams becomes difficult, which can lead to disruptions in the
      identification of behaviorally relevant targets. This study investigated the
      benefit of providing simple visual cues for when and/or where a target would
      occur in a complex acoustic mixture. Importantly, the visual cues provided no
      information about the target content. In separate experiments, human subjects
      either identified learned birdsongs in the presence of a chorus of unlearned
      songs or recalled strings of spoken digits in the presence of speech maskers. A
      visual cue indicating which loudspeaker (from an array of five) would contain the
      target improved accuracy for both kinds of stimuli. A cue indicating which time
      segment (out of a possible five) would contain the target also improved accuracy,
      but much more for birdsong than for speech. These results suggest that in real
      world situations, information about where a target of interest is located can
      enhance its identification, while information about when to listen can also be
      helpful when targets are unfamiliar or extremely similar to their competitors.

PMID- 17453316
TI  - Comment on Clowes et al.: device-specific thresholds to diagnose osteoporosis at
      the proximal femur: an approach to interpreting peripheral bone measurements in
      clinical practice.

PMID- 17453321
TI  - Urology out-patient non-attenders: are we wasting our time?
AB  - BACKGROUND: Out-patient non-attendance leads to inefficiency and patient
      morbidity. AIMS AND METHODS: A phone survey of urology out-patient non-attenders
      over 1-month was performed to determine reasons for non-attendance, to identify
      patients who could be discharged, and the manner in which patients want
      reminders. RESULTS: Seventy-six non-attenders were contacted. Fourteen were GP
      referred new patients. The reason for non-attendance (n = 10) was due to patient
      issues. Of the patients due for review (n = 62), it was a first non-attendance in
      56. Only 41 (66%) claimed to have received notification or appointment cards.
      Eight patients said they were written to and 13 (21%) denied either receiving a
      written notification or an appointment card. Only eight patients rang to
      confirm/change their appointment. Ninety-nine percent said that they would like a
      further appointment by text message (34%), phone (37%), letter (36%) or email
      (6%). CONCLUSIONS: We now hope to implement a number of methods to further reduce
      non-attendance rates based on the findings in this study.

PMID- 17453322
TI  - The circadian nuances of hypertension: a reappraisal of 24-h ambulatory blood
      pressure measurement in clinical practice.
AB  - Ambulatory blood pressure measurement has been in use in clinical practice for
      nearly half a century. However, despite the benefits the technique brings to
      managing patients with hypertension it is much under-used in practice. The
      purpose of this review is to examine critically the information that can be
      derived from the technique and to highlight the application of this evidence in
      clinical practice.

PMID- 17453323
TI  - A male-produced sex pheromone from the neotropical redbanded stink bug,
      Piezodorus guildinii (W).
AB  - The male-produced sex pheromone of the neotropical redbanded stink bug,
      Piezodorus guildinii (W.) (Hemiptera: Pentatomidae), a serious pest of soybean in
      Central and South America, was identified as the sesquiterpene hydrocarbon beta
      sesquiphellandrene by coupled gas chromatography-mass spectrometry and laboratory
      bioassays. The identity was confirmed by comparison with an authentic standard,
      and its absolute configuration was determined to be (7R)-(+)-beta
      sesquiphellandrene. The mean rate of release was approximately 40 ng d(-1) male(
      1). The compound was found only in extracts from sexually mature males.
      Laboratory olfactometer bioassays showed that 200 ng of the synthetic compound
      applied to a filter paper strip was as attractive to female bugs as odors from
      five 15-d-old live males, an airborne extract from males, or the fraction of the
      extract that contained (7R)-(+)-beta-sesquiphellandrene.

PMID- 17453324
TI  - Predatory behavior of Polistes dominulus wasps in response to cardenolides and
      glucosinolates in Pieris napi caterpillars.
AB  - To examine how plant allelochemicals in prey affect foraging choices made by
      generalist predator paper wasps, Polistes dominulus (Vespidae), we compared
      predation on Pieris napi (Pieridae) caterpillars reared on host plants with
      different allelochemicals. In naturalistic behavioral choice experiments, free
      flying wasps chose between living pierids reared on cabbage (Brassica oleracea),
      which lacks deterrent allelochemicals, or alternate host plants with potentially
      deterrent allelochemicals. The alternative host plants were: wormwood mustard,
      (Erysimum cheiranthoides: Brassicaceae), which contains cardenolides; nasturtium
      (Tropaeolum majus: Tropaeolaceae) with high concentrations of chlorogenic acid;
      and black mustard (Brassica nigra: Brassicaceae) with high concentrations of the
      aliphatic glucosinolate, sinigrin. Although wasps captured equal numbers of
      caterpillars reared on cabbage and each alternate host plant, they spent
      significantly longer handling prey from the alternate host plants as they
      selectively removed the caterpillar's gut, which contained the plant material.
      This was true even if the caterpillar did not sequester toxins in its tissues, as
      revealed by high performance liquid chromatography (HPLC) analysis of Erysimum
      reared pierids. Because handling time is longer, predators that capture pierids
      containing non-sequestered allelochemicals experience an overall reduction in
      foraging rate that may translate into a fitness cost.

PMID- 17453325
TI  - Examining DSM-IV criteria for pathological gambling: psychometric properties and
      evidence from cognitive biases.
AB  - We examined the DSM-IV criteria for pathological gambling as assessed with the
      DSM-IV-based Diagnostic Interview for Gambling Severity (DIGS; Winters, Specker,
      & Stinchfield, 2002). We first analyzed the psychometric properties of the DIGS,
      and then assessed the extent to which performance on two judgment and decision
      making tasks, the Georgia Gambling Task (Goodie, 2003) and the Iowa Gambling Task
      (Bechara, Damasio, Damasio, & Anderson, 1994), related to higher reports of
      gambling pathology. In a sample of frequent gamblers, we found strong
      psychometric support for the DSM-IV conception of pathological gambling as
      measured by the DIGS, predictive relationships between DIGS scores and all
      cognitive performance measures, and significant differences in performance
      measures between individuals with and without pathological gambling. Analyses
      using suggested revisions to the pathological gambling threshold (Stinchfield,
      2003) revealed that individuals meeting four of the DSM-IV criteria aligned
      significantly more with pathological gamblers than with non-pathological
      gamblers, supporting the suggested change in the cutoff score from five to four
      symptoms. Discussion focuses on the validity of the DSM-IV criteria as assessed
      by the DIGS and the role of cognitive biases in pathological gambling.

PMID- 17453326
TI  - GPs and problem gambling: can they help with identification and early
      intervention?
AB  - General Practitioners (GPs) are well placed to identify problem gamblers and
      provide early intervention. To date there is no evidence to suggest that GP's are
      routinely screening patients for potential gambling problems. This paper
      discusses the prevalence of problem gambling, the links with other health
      problems and ways that GPs can assist. Results from a pilot project that provided
      educational resources to GPS are also discussed. Suitable screening tools are
      available that could easily be used by GPs to assess the possibility of gambling
      problems in patients who may be at increased risk but do not seek help. Early
      identification and intervention may help prevent a gambling habit escalating to a
      serious problem. More work needs to be done to increase awareness with GPs of the
      extent of problem gambling in our community and to alert patients to the fact
      that gambling can affect their health and that GPs can help.

PMID- 17453327
TI  - Single-molecule detection of reactive oxygen species: application to
      photocatalytic reactions.
AB  - In this review, we have focused on the oxidation reactions of single dye
      molecules by reactive oxygen species (ROS). The methodologies for the single
      molecule detection of ROS, such as hydroxyl radical (HO*), singlet oxygen
      (O(2)(a(1)Delta(g))), and hydrogen peroxide (H2O2), have been introduced together
      with examples. In particular, a successful application using the single-molecule
      fluorescence technique for the investigation of the TiO2 photocatalytic oxidation
      reactions is demonstrated in detail.

PMID- 17453328
TI  - Mediating variables in a parent based intervention to reduce skin cancer risk in
      children.
AB  - The present study examined theoretical mediators of a parent-based intervention
      on sunbathing tendencies and sunburn frequencies based on the work of Turrisi et
      al. [Turrisi, R., Hillhouse, J., Heavin, S., Robinson, J., Adams, M., & Berry, J.
      (2004). Journal of Behavioral Medicine, 27, 393-412.]. Three hundred and forty
      parents in two regions of the United States were educated about the dangers of
      risky sun behavior and how to convey information about skin cancer prevention to
      their children. Attitudes toward sunbathing, health beliefs, appearance beliefs,
      and social normative beliefs were examined and found to be significant mediators
      of program effects on sunbathing tendencies and sunburn frequencies. The findings
      are discussed with respect to maximizing the effectiveness of future skin cancer
      interventions with children.

PMID- 17453329
TI  - Forgiveness, health, and well-being: a review of evidence for emotional versus
      decisional forgiveness, dispositional forgivingness, and reduced unforgiveness.
AB  - The extant data linking forgiveness to health and well-being point to the role of
      emotional forgiveness, particularly when it becomes a pattern in dispositional
      forgivingness. Both are important antagonists to the negative affect of
      unforgiveness and agonists for positive affect. One key distinction emerging in
      the literature is between decisional and emotional forgiveness. Decisional
      forgiveness is a behavioral intention to resist an unforgiving stance and to
      respond differently toward a transgressor. Emotional forgiveness is the
      replacement of negative unforgiving emotions with positive other-oriented
      emotions. Emotional forgiveness involves psychophysiological changes, and it has
      more direct health and well-being consequences. While some benefits of
      forgiveness and forgivingness emerge merely because they reduce unforgiveness,
      some benefits appear to be more forgiveness specific. We review research on
      peripheral and central nervous system correlates of forgiveness, as well as
      existing interventions to promote forgiveness within divergent health settings.
      Finally, we propose a research agenda.

PMID- 17453330
TI  - Negative thinking as a coping strategy mediator of pain and internalizing
      symptoms in adolescents with sickle cell disease.
AB  - The objective of this study was to examine the role of coping strategies,
      specifically negative thinking, in mediating the association of pain with
      symptoms of anxiety and depression in adolescents with sickle cell disease. Fifty
      two 12-18-year-old adolescents with sickle cell disease completed a daily pain
      diary and paper-and-pencil measures of pain, pain coping, depression and anxiety.
      Symptoms of depression and anxiety were within the non-clinical range.
      Preliminary analyses indicated that lower family income was associated with
      higher reports of pain and negative thinking. Mediation regression analyses
      supported negative thinking as mediating the association of: (1) pain intensity
      with depression, and (2) pain interference with daily activities with anxiety.
      Findings highlight negative thinking as a factor compromising adolescents'
      adaptation to sickle cell pain; however, further investigation is required to
      determine the mediating influence of pain coping. Associations for lower income
      emphasize the multiple risk factors experienced by many of these adolescents.

PMID- 17453331
TI  - Twin pair resemblance for psychiatric hospitalization in the Swedish Twin
      Registry: a 32-year follow-up study of 29,602 twin pairs.
AB  - BACKGROUND: Allgulander et al. (Allgulander C, Nowak J, Rice JP (1991) Acta
      Psychiatr Scand 83, 12) published twin pair analyses of psychiatric
      hospitalization for like-sex pairs from the Swedish Twin Registry born 1926-1958.
      As noted in a subsequent letter (Allgulander C, Nowak J, Rice JP (1992) Acta
      Psychiatr Scand 86, 421), several features of the original study resulted in
      under-ascertainment of cases and underestimated heritability, particularly for
      alcoholism. The present report updates the prior results by using 17 additional
      years of follow-up, including members of opposite-sex twin pairs, and addressing
      biases arising from cohort effects and from excluding pairs with unknown
      zygosity. METHODS: Registry records for 29,602 twin pairs born 1926-1958 were
      matched against national databases of psychiatric and medical hospitalizations
      from 1972-2000 to obtain ICD diagnostic codes. Zygosity was known for 10,903
      opposite-sex pairs and 15,401 like-sex pairs who participated previously in
      research. Twin-pair resemblance and genetic and environmental variance
      proportions were estimated for hospitalization for alcoholism, affective
      disorders, psychosis, and (in females) anxiety disorders. RESULTS:
      Hospitalization rates during the ascertainment window were: alcoholism: males =
      3.67%, females = 0.94%; affective disorders: males = 1.99%, females = 2.75%;
      anxiety disorders: males = 0.46%, females = 0.74%; and psychotic disorders: males
      = 1.70%, females = 1.96%. Twins from like-sex pairs with unknown zygosity had
      significantly higher prevalences than those with known zygosity. Tetrachoric
      correlations and heritability estimates were affected by the method used to model
      unknown zygosity and cohort effects. CONCLUSIONS: Inclusion of additional follow
      up information, opposite-sex twin pairs, age-adjustment, and use of current ICD
      definitions yielded higher heritability estimates for alcoholism, anxiety
      disorders, and psychosis than previously published for this nationally
      representative sample of twins from Sweden. The results show that relatively
      small selection biases can alter twin study results and underscore the importance
      of addressing under-ascertainment of cases in genetic research based on
      volunteers.

PMID- 17453332
TI  - The feasibility of computerized patient self-assessment at mental health clinics.
AB  - OBJECTIVES: Improving the quality of care for severe mental illness (SMI) has
      been difficult because patients' clinical information is not readily available.
      Audio computer-assisted self-interviewing (ACASI) supports data collection by
      asking patients waiting for appointments clinical questions visually and aurally.
      It has improved outcomes for many disorders. While reliable and accurate for SMI
      in research settings, this study assesses questions about ACASI's feasibility in
      usual care. DESIGN: Patient and provider surveys and provider focus groups after
      12 months of ACASI implementation. SETTING: Two outpatient mental health clinics
      in Los Angeles, one run by the Department of Veterans Affairs and the other by
      Los Angeles County Department of Mental Health. PARTICIPANTS: 266 patients with
      SMI and 14 psychiatrists. INTERVENTION: Patients completed an ACASI survey on
      symptoms, drug use, medication adherence and side-effects by internet using a
      touch-screen monitor. A 1-page report summarizing each patient's results was
      printed and given to providers by patients during appointments. MAIN OUTCOME
      MEASURE: Feedback surveys (patients and psychiatrists) and focus groups and
      interviews (psychiatrists) assessed usability, usefulness, effects on treatment,
      and barriers to sustaining ACASI. RESULTS: Patients believed the PAS was
      enjoyable, easy to learn and use, and that it improved communication with their
      psychiatrists. Providers believed the PAS was easy to use, had a small impact on
      care, could be improved by being more detailed and comprehensive, and requires
      outside support to continue its use. CONCLUSIONS: ACASI was easy to use and
      enhanced communication. Systems like this can be a valuable part of quality
      improvement projects.

PMID- 17453333
TI  - Isolation and sequence analysis of wheat NBS-LRR type disease resistance gene
      analogs using degenerate PCR primers.
AB  - Isolation of disease resistance gene analogs (RGAs) using the conserved motifs of
      the resistance genes has attracted considerable attention since it was first
      reported more than a decade ago. In this study, RGAs are isolated using homology
      based PCR to target the nucleotide binding site (NBS) conserved regions from
      hexaploid wheat varieties and a few accessions of wild types. Based on sequence
      similarity analysis, 83 of the sequenced clones were clustered as groups. Of
      these RGAs, 40 were in the NBS-LLR class, containing kinase-1a (GGVGKTT or
      GGVGKTA), kinase-2 (KRFLIVLDDXW), kinase-3a (GSXIVVITTR or GCXVLATTR), and the
      GLPL motif of the NBS-spanning region. Among these, 15 contained possible intron
      regions, similar to Avena sativa O2 NBS-LLR type disease resistance gene
      (AF078874), and one to Rpm1 of rice and Yr10 and Lr10 of wheat. To our knowledge,
      this is the first observation of an intronic site within the P-loop domain of
      wheat RGAs. We detected an unspecified motif (VMVCVS) between the kinase-1a and
      kinase-2 domains within our clones. Additionally, one of the clones showed
      replacement with the kinase-3a motif with an undefined sequence.

PMID- 17453334
TI  - Transactivation of ERalpha by Rosiglitazone induces proliferation in breast
      cancer cells.
AB  - In the present study, we demonstrate that Rosiglitazone (Rosi), a
      thiazolidinedione and PPARgamma agonist, induces ERE (Estrogen Receptor Response
      Element) reporter activity, pS2 (an endogenous ER gene target) expression, and
      proliferation of ER positive breast cancer (MCF-7) cells. By performing a dose
      response assay, we determined that high concentrations of Rosi inhibit
      proliferation, while low concentrations of Rosi induce proliferation. Using the
      anti-estrogen ICI, ER negative breast cancer (MDA-MB-231) cells, and a prostate
      cancer cell line (22Rv1) deficient in both ERalpha and PPARgamma, we determined
      that Rosiglitazone-induced ERE reporter activation and proliferation is through
      an ERalpha dependent mechanism. Rosiglitazone-induced ERE activation is also
      dependent on activation of the Extracellular Signal-Regulated Kinase-Mitogen
      Activated Protein Kinase (ERK-MAPK) pathway, since it is inhibited by co
      treatment with U0126, a specific inhibitor of this pathway. We also demonstrate
      that when ERalpha and PPARgamma are both present, they compete for Rosi,
      inhibiting each others transactivation. To begin to unravel the pharmacological
      mechanism of Rosi-induced ER activation, sub-maximally effective concentrations
      of E(2) were used in combination with increasing concentrations of Rosi in
      luciferase reporter assays. From these assays it appears that E(2) and Rosi both
      activate ERalpha via similar pharmacological mechanisms. Furthermore sub
      maximally effective concentrations of E(2) and Rosi additively increase both ERE
      reporter activity and MCF-7 cell proliferation. The results of this study may
      have clinical relevancy for Rosi's use both as an anti-diabetic in post
      menopausal women and as an anti-cancer drug in women with ER positive breast
      cancer.

PMID- 17453335
TI  - Greek BRCA1 and BRCA2 mutation spectrum: two BRCA1 mutations account for half the
      carriers found among high-risk breast/ovarian cancer patients.
AB  - 127 Greek breast/ovarian cancer families were screened for germline BRCA1/2
      mutations by dHPLC followed by direct sequencing. Our results indicated 16 and 5
      breast/ovarian cancer families bearing deleterious mutations in the BRCA1 and
      BRCA2 genes, respectively. Two novel BRCA2 germline mutations (G4X and 3783del10)
      are reported here for the first time. Subsequent compilation of our present
      findings with previously reported mutation data reveals that in a total of 287
      Greek breast/ovarian cancer families, 46 and 13 carry a deleterious mutation in
      BRCA1 and BRCA2, respectively. It should be noted that two BRCA1 mutations,
      5382insC and G1738R, both located in exon 20, account for 46% of the families
      found to carry a mutation. Based on our mutation analysis results, we propose
      here a hierarchical, cost-effective BRCA1/2 mutation screening protocol for
      individuals of Greek ethnic origin. The suggested protocol can impact on the
      clinical management of breast-ovarian cancer families on a national healthcare
      system level.

PMID- 17453336
TI  - Decline in breast cancer incidence after decrease in utilisation of hormone
      replacement therapy.
AB  - Hormone replacement therapy (HRT) has been implicated as a risk factor for breast
      cancer and the use of HRT has decreased substantially in general population over
      the last years. Recently, there are first indications that breast cancer
      incidence has started declining. We examined recent breast cancer incidence and
      actual data on HRT utilisation in Schleswig-Holstein, Germany, to find out
      population based evidence on decreasing breast cancer incidence and its possible
      relationship with reduced HRT usage. Breast cancer incidence is taken from the
      population based cancer registry of Schleswig-Holstein. HRT data was extracted
      from a cohort of 102,000 women taking part in a quality assurance project in
      breast cancer diagnosis for the years 2001-2005. The annual percentage change in
      incidence of breast cancer and HRT utilisation was measured by linear regression.
      There is a linear decline in HRT utilisation among less than 50 years group, 50
      69 years group and all age group women between the years 2001 and 2005. Breast
      cancer incidence decreased between the years 2001 and 2005 for more than 50 years
      old and all age group, but not in the younger than 50 years women. The decline of
      breast cancer incidence started about two years after the HRT decline. Breast
      cancer incidence decline and decreased HRT utilisation showed a high correlation.
      A drastic change in age-incidence relationship in breast cancer has taken place,
      the change is likely to continue and in future it has to be monitored closely
      with HRT use and other possible explanations.

PMID- 17453338
TI  - Methylenetetrahydrofolate reductase (MTHFR) and breast cancer risk: a nested-case
      control study and a pooled meta-analysis.
AB  - Encouraged by recent studies on the MTHFR 677C>T polymorphism and breast cancer
      risk that suggested an association of the 677 TT genotype with increased breast
      cancer susceptibility in premenopausal women, we performed an analysis of the
      relationship between breast cancer risk and the MTHFR 677C>T polymorphism in 210
      premenopausal breast cancer patients and sex- and agematched healthy control
      subjects. Our data show a trend for a higher MTHFR 677T allele frequency in
      breast cancer cases (61.9%) than in controls (51.5%, P = 0.082) supporting the
      results of previous studies.

PMID- 17453337
TI  - Non-synonymous polymorphisms in the circadian gene NPAS2 and breast cancer risk.
AB  - Three known non-synonymous polymorphisms (Ala394Thr, Ser471Leu and Pro690Ala) in
      the largest circadian gene, Neuronal PAS domain protein 2 (NPAS2), were genotyped
      in a breast cancer case-control study conducted in Connecticut, USA (431 cases
      and 476 controls). We found that women with the heterozygous Ala394Thr genotype
      were significantly associated with breast cancer risk compared to those with the
      common homozygous Ala394Ala (OR = 0.61, 0.46-0.81, P = 0.001). This is the first
      evidence demonstrating a role of the circadian gene NPAS2 in human breast cancer,
      suggesting that genetic variations in circadian genes might be a novel panel of
      biomarkers for breast cancer risk.

PMID- 17453339
TI  - Unique resistance of breast carcinoma cell line T47D to TRAIL but not anti-Fas is
      linked to p43cFLIP(L).
AB  - The majority of breast cancer cell lines are resistant to tumor necrosis factor 
      related apoptosis inducing ligand (TRAIL) induced apoptosis. TRAIL and Fas
      receptor death-inducing signaling complex (DISCs) formation are similar and
      involve ligand-dependent recruitment of FADD and caspase-8. We have found that
      the breast carcinoma cell line T47D is an unusual example of selective
      sensitivity to anti-Fas mAb treatment but resistant to TRAIL. Therefore, a
      detailed comparison of these two signaling pathways in one cell line should
      provide insight into the mechanism of TRAIL resistance. We observed that only
      anti-Fas mAb induces caspase activation and cell death in T47D. Further, FADD and
      caspase-8 interact with both TRAIL-R1 and TRAIL-R2, and that the amount of
      caspase-8 recruited by Fas-, TRAIL-R1 and TRAIL-R2 are the same. cFLIP(S) and
      cFLIP(R )isoforms block death receptor-induced apoptosis by inhibiting caspase-8
      activation at the DISC; the role of cFLIP(L )at the DISC is still controversial.
      It has been suggested that the presence of the cleaved form of FLIP(L)-p43 at the
      DISC prevents caspase-8 cleavage. We found that both TRAIL and anti-Fas mAb
      induced DISCs contain the cleaved form of p43 cFLIP(L) and its amount at the Fas
      DISC was higher compared to the TRAIL DISC. We also found that inhibition of
      cFLIP(L) expression in T47D cells decreased Fas-mediated caspase-8 activation and
      activation of effector caspases. We propose that in T47D p43 cFLIP(L) in the Fas
      DISC may promote caspase-8 activation. The mechanism by which different amounts
      of p43cFLIP(L) regulates caspase-8 activation remains to be investigated.

PMID- 17453340
TI  - Estrogen receptor alpha polymorphisms and postmenopausal breast cancer risk.
AB  - BACKGROUND: The estrogen receptor alpha (ESR1) is a mediator of estrogen response
      in the breast. The most studied variants in this gene are the PvuII and XbaI
      polymorphisms, which have been associated to lower sensitivity to estrogen. We
      evaluated whether these polymorphisms were associated with breast cancer risk by
      means of an association study in a population of Caucasian postmenopausal women
      from the Rotterdam study and a meta-analysis of published data. METHODS: The
      PvuII and XbaI polymorphisms were genotyped in 3,893 women participants of the
      Rotterdam Study. Baseline information was obtained through a questionnaire. We
      conducted logistic regression analyses to assess the risk of breast cancer by
      each of the ESR1 genotypes. Meta-analyses of all publications on these relations
      were done by retrieving literature from Pubmed and by further checking the
      reference lists of the articles obtained. RESULTS: There were 38 women with
      previously diagnosed breast cancer. During follow-up, 152 were additionally
      diagnosed. The logistic regression analyses showed no difference in risk for
      postmenopausal breast cancer in carriers of the PvuII or XbaI genotypes neither
      in overall, incident or prevalent cases. No further evidence of a role of these
      variants was found in the meta-analysis. CONCLUSIONS: Our results suggest that
      the ESR1 polymorphisms do not play a role in breast cancer risk in Caucasian
      postmenopausal women.

PMID- 17453341
TI  - EZH2 regulates the transcription of estrogen-responsive genes through association
      with REA, an estrogen receptor corepressor.
AB  - Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase polycomb group
      (PcG) protein, which has been implicated in the process of cellular
      differentiation and cancer progression for both breast and prostate cancer.
      Although transcriptional repression by histone modification appears to contribute
      to the process of cellular differentiation, it is unclear what mediates the
      specificity of PcG proteins. Since EZH2 requires a binding partner for its
      histone methyltransferase activity, we surmised that evaluating interacting
      proteins might shed light on how the activity of EZH2 is regulated. Here we
      describe the identification of a novel binding partner of EZH2, the repressor of
      estrogen receptor activity (REA). REA functions as a transcriptional corepressor
      of the estrogen receptor and can potentiate the effect of anti-estrogens. REA
      expression levels have also previously been associated with the degree of
      differentiation of human breast cancers. We show here that EZH2 can also mediate
      the repression of estrogen-dependent transcription, and that moreover, the
      ability of both REA and EZH2 to repress estrogen-dependent transcription are
      mutually dependent. These data suggest that EZH2 may be recruited to specific
      target genes by its interaction with the estrogen receptor corepressor REA. The
      identification of a novel interaction between EZH2 and REA, two transcription
      factors that have been linked to breast cancer carcinogenesis, may lead to
      further insights into the process of deregulated gene expression in breast
      cancer.

PMID- 17453342
TI  - Exploring the two-gene ratio in breast cancer--independent roles for HOXB13 and
      IL17BR in prediction of clinical outcome.
AB  - BACKGROUND: The two-gene expression ratio HOXB13:IL17BR has been proposed to
      predict the outcome of tamoxifen-treated breast cancer patients. We intended to
      examine whether this ratio can predict the benefit of 5 years vs. 2 years of
      tamoxifen treatment of postmenopausal patients. A further objective was to
      investigate any prognostic effects of the ratio in systematically untreated
      premenopausal patients. Based on the current knowledge of HOXB13 and IL17BR, we
      hypothesized that these genes may have individual prognostic or predictive power.
      PATIENTS AND METHODS: Expression of HOXB13 and IL17BR were quantified by real
      time PCR in tumors from 264 randomized postmenopausal patients and 93
      systemically untreated premenopausal patients. RESULTS: A high HOXB13:IL17BR
      ratio was associated with aggressive tumor characteristics, as were low levels of
      IL17BR alone. The ratio and HOXB13 alone predicted recurrence-free survival after
      endocrine treatment, with a benefit of prolonged treatment in estrogen receptor
      positive patients correlated to a low ratio (recurrence rate ratio: RR = 0.39; P
      = 0.030), or low expression of HOXB13 (RR = 0.37; P = 0.015). No difference in
      recurrence-free survival was seen for the high ratio or high HOXB13 subgroups.
      The predictive value of HOXB13 and HOXB13:IL17BR was significant in multivariate
      analysis. In the systemically untreated cohort, only IL17BR showed independent
      prognostic significance. CONCLUSION: We conclude that the ratio or HOXB13 alone
      can predict the benefit of endocrine therapy, with a high ratio or a high
      expression rendering patients less likely to respond. We have also shown that
      IL17BR might be an independent prognostic factor in breast cancer.

PMID- 17453344
TI  - Acute heart failure: is there a role for surgery?
AB  - Many of the disorders and lesions leading to acute heart failure can be treated
      surgically. Modern surgical techniques like the off pump coronary surgery, newer
      techniques for the surgical treatment of the mechanical complications of acute MI
      and valvular reparative techniques have been added to the surgical armamentarium
      in recent years. Modern ventricular assist devices have started their career in
      the clinical arena promising to be less invasive. At the same time the spectrum
      of indications for mechanical circulatory support continues to witness a rapid
      expansion. Technical advances have led to an evolution of surgical strategies.
      Heart failure surgery is now in a position to offer improved outcomes, avoidance
      of recurrence of acute heart failure or the development of advanced chronic heart
      failure.

PMID- 17453345
TI  - History of trauma and dissociative symptoms among patients with obsessive
      compulsive disorder and social anxiety disorder.
AB  - We aimed to compare the history of trauma and the profile and severity of
      dissociative symptoms of patients with obsessive-compulsive disorder (OCD) to
      those of patients with social anxiety disorder (SAD). Patients with OCD (n = 34)
      and patients with SAD (n = 30) were examined with the following instruments:
      Trauma History Questionnaire (THQ), Dissociative Experience Scale (DES),
      Obsessive-Compulsive Inventory (OCI), Liebowitz Social Anxiety Scale (LSAS), Beck
      Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Patients with OCD
      reported significantly lower rates of exposure to traumatic events. Nevertheless,
      the severity of dissociative symptoms was not significantly different between the
      groups. Regression analyses showed that, while the OCI scores better predicted
      the variance on DES scores in the OCD sample, the LSAS and the BAI better
      predicted the variance on the DES among patients with SAD. Patients with OCD are
      probably less vulnerable to some types of traumatic experiences. Dissociative
      symptoms may cut across different anxiety disorders.

PMID- 17453346
TI  - Protein interfacial pocket engineering via coupled computational filtering and
      biological focusing criterion.
AB  - To engineer bio-macromolecular systems, protein-substrate interactions and their
      configurations need to be understood, harnessed, and utilized. Due to the
      inherent large numbers of combinatorial configurations and conformational
      complexity, methods that rely on heuristics or stochastics, such as practical
      computational filtering (CF) or biological focusing (BF) criterions, when used
      alone rarely yield insights into these complexes or successes in (re)designing
      them. Here we use a coupled CF-BF criterion upon an amenable interfacial pocket
      (IP) of a protein scaffold complexed with its substrate to undergo residue
      replacement and R-group refinement (R4) to filter out energetically unfavorable
      residues and R-group conformations, and focus in on those that are evolutionarily
      favorable. We show that this coupled filtering and focusing can efficiently
      provide a putative engineered IP candidate and validate it computationally and
      empirically. The CF-BF criterion may permit holistic understanding of the nuances
      of existing protein IPs and their scaffolds and facilitate bioengineering efforts
      to alter substrate specificity. Such approach may contribute to accelerated
      elucidation of engineering principles of bio-macromolecular systems.

PMID- 17453347
TI  - Mapping melanoma lymphoscintigraphy data onto a 3D anatomically based model.
AB  - This study describes three-dimensional (3D) visualization of two-dimensional (2D)
      melanoma lymphatic mapping data, to provide a framework for analysis of melanoma
      spread patterns and a platform for recording new lymphoscintigraphy (LS) data
      more accurately in 3D. Specifically, the Sydney Melanoma Unit's LS database of
      over 5000 patients' primary cutaneous melanoma sites and sentinel lymph nodes
      have been mapped from 2D images onto a 3D anatomically based model. Anatomically
      accurate model geometries were created using the Visible Human dataset, giving a
      bicubic finite element skin mesh and discrete sentinel lymph node model. The full
      dataset of 2D melanoma site coordinates, excluding the head and neck, has been
      transformed onto this 3D skin mesh via free-form deformation and projection
      techniques. Sentinel lymph nodes were mapped onto the generic lymph node model
      for each patient. Preliminary spatial analysis indicates that a patient with a
      primary melanoma on the torso around the waist (on the standardized 3D model this
      region is 180 mm above and 130 mm below the umbilicus) with lymphatic drainage to
      the left axilla or left groin, will have a 17.7% probability of dual drainage to
      both node fields, with 95% confidence limits between 14.5 and 21.0%.

PMID- 17453348
TI  - Relative contributions of collagen and elastin to elasticity of the vocal fold
      under tension.
AB  - This study examined the contributions of collagen and elastin to the tensile
      elastic properties of the vocal fold lamina propria. Uniaxial stress-strain
      responses of vocal fold cover and vocal ligament specimens from 20 human larynges
      (12 males, 8 females) were quantified with sinusoidal stretch-release deformation
      in vitro. Mid-coronal sections of 12 specimens were examined histologically with
      Masson's trichrome and elastin van Gieson stain to quantify the relative
      densities of collagen and elastin fibers. Results showed that significantly
      higher levels of collagen were found in the male vocal fold than female, for both
      the cover and the ligament. For male there was a significantly higher level of
      elastin in the cover than in the ligament. On average, the elastic modulus of the
      male cover was about twice that of the female at high-tensile strain (35-40%),
      whereas the male ligament was 3-5 times stiffer than the female in the same
      range. The ligament was stiffer than the cover for male, but the opposite was
      observed for female. These findings suggested that collagen and elastin could
      contribute differentially to elasticity of the cover and the ligament. The data
      may provide guidance for surgical reconstruction and tissue engineering of
      different lamina propria layers.

PMID- 17453349
TI  - Emerging disease burdens and the poor in cities of the developing world.
AB  - Patterns of future urban growth, combined with advances in the treatment of
      traditional scourges of communicable diseases, will cause a shift in the burden
      of disease toward category 2 (noncommunicable) and 3 (injury) conditions over the
      next 30 years. Communicable diseases, particularly HIV/AIDs, will continue to be
      the most important killers among the poor. However, new risks will emerge for
      several reasons. First, the marked sprawl of cities in the developing world will
      make access to care more difficult. Second, increasing motor vehicles and the
      likelihood of inadequate infrastructure will make air pollution and accidents in
      road traffic more common than in the past. Third, impoverished urban populations
      have already shown a propensity toward undernourishment, and its obverse,
      obesity, is already emerging as a major risk. Also, the large projected increase
      in slums suggests that violence and homicide will become a more important burden
      of health, and very large hazards will be created by fire-prone, insubstantial
      dwellings that will house nearly two billion people by 2030. In addition,
      decentralized governance will exacerbate the tensions and discontinuities that
      have plagued the management of health issues on the urban fringe over the past
      decade. Accordingly, public health agencies will need to adjust to the regional
      and country-specific factors to address the changing profile of risk. This
      analysis suggests that four factors--levels of poverty, speed of city growth,
      sprawl in cities, and degree of decentralization--will have importance in shaping
      health strategies. These factors vary in pace and intensity by region, suggesting
      that health care strategies for Category II and III conditions will need to be
      differentiated by region of the world. Also, interventions will have to rely
      increasingly on actors outside the ranks of public health specialists.

PMID- 17453350
TI  - Role of undecan-2-one on ethanol-induced apoptosis in HepG2 cells.
AB  - Based on the reduced expression of ethanol-oxidizing enzymes in human
      hepatocellular carcinoma (HepG2) cells, we analyzed the role of nonoxidative
      metabolites in ethanol-induced apoptosis in HepG2 cells. For this purpose, an
      analysis of volatile metabolites of ethanol using ion-mobility spectrometry and
      gas chromatography-mass spectrometry was performed. HepG2 cells exposed to 1
      mmol/L ethanol exhibited significant synthesis of undecan-2-one compared to
      untreated cells. Undecan-2-one is a fatty acid ethyl ester metabolite synthesized
      through a nonoxidative pathway. Undecan-2-one had a dose-dependent cytotoxic
      effect on HepG2 cells as shown by release of lactate dehydrogenase (LDH). The
      most notable finding of this study was the potentiation of ethanol-induced
      apoptosis demonstrated by an increased apoptotic rate induced by undecan-2-one in
      ethanol-treated HepG2 cells. The data presented in this study contribute to the
      better understanding of the molecular mechanisms of ethanol exposure at low
      concentration in HepG2 cells, a human hepatocellular carcinoma-derived cell line.

PMID- 17453351
TI  - Combined administration of iron and monoisoamyl-DMSA in the treatment of chronic
      arsenic intoxication in mice.
AB  - Co-administration of iron in combination with monoisoamyl dimercaptosuccinic acid
      (MiADMSA) against chronic arsenic poisoning in mice was studied. Mice preexposed
      to arsenic (25 ppm in drinking water for 6 months) mice were treated with MiADMSA
      (50 mg/kg, intraperitoneally) either alone or in combination with iron (75 or 150
      mg/kg, orally) once daily for 5 days. Arsenic exposure led to a significant
      depletion of blood delta-aminolevulinic acid dehydratase (ALAD) activity,
      hematocrit, and white blood cell (WBC) counts accompanied by small decline in
      blood hemoglobin level. Hepatic reduced glutathione (GSH) level, catalase and
      superoxide dismutase (SOD) activities showed a significant decrease while,
      oxidized glutathione (GSSG) and thiobarbituric acid-reactive substances (TBARS)
      levels increased on arsenic exposure, indicating arsenic-induced hepatic
      oxidative stress. Liver aspartate and alanine transaminases (AST and ALT)
      activities also decreased significantly on arsenic exposure. Kidney GSH, GSSG,
      catalase level and SOD activities remained unchanged, while, TBARS level
      increased significantly following arsenic exposure. Brain GSH, glutathione
      peroxidase (GPx), and SOD activities decreased, accompanied by a significant
      elevation of TBARS level after chronic arsenic exposure. Treatment with MiADMSA
      was marginally effective in reducing ALAD activity, while administration of iron
      was ineffective when given alone. Iron when co-administered with MiADMSA restored
      blood ALAD activity. Administration of iron alone had no beneficial effects on
      hepatic oxidative stress, while in combination with MiADMSA it produced
      significant decline in hepatic TBARS level compared to the individual effect of
      MiADMSA. Renal biochemical variables were insensitive to any of the treatments.
      Combined administration of iron with MiADMSA also had no additional beneficial
      effect over the individual protective effect of MiADMSA on brain oxidative
      stress. Interestingly, combined administration of iron with MiADMSA provided more
      pronounced depletion of blood arsenic, while no additional beneficial effects on
      tissue arsenic level over the individual effect of MiADMSA were noted. The
      results lead us to conclude that iron supplementation during chelation has some
      beneficial effects particularly on heme synthesis pathway and blood arsenic
      concentration.

PMID- 17453352
TI  - Modulation of multidrug resistance protein (MRP1/ABCC1) expression: a novel
      physiological role for ouabain.
AB  - Besides being a (Na(+),K(+))-ATPase inhibitor, high doses of the hormone ouabain
      have also been reported to modulate both the expression and activity of proteins
      belonging to the ATP binding cassette family of transporters, such as ABCC7
      (CFTR), ABCB1 (P-glycoprotein), and ABCC1 (MRP1). Although these proteins are
      present in the kidney, only ABCB1 has a putative physiological role in this
      organ, secreting endobiotics and xenobiotics. In the present work, we studied the
      relationship between ouabain and ABCC1 expression and function, aiming to
      establish a physiological role for ouabain. It was observed that prolonged (24 h)
      but not short (30 min) incubation with 1 nmol/L or higher ouabain concentrations
      decreased the expression of ABCC1 protein and induced its mRNA expression. This
      decrease was rapidly reversible, reaching control levels after incubation of
      cells in ouabain-free medium for 3 h, denoting a hormonal action. Moreover,
      concentrations equal or higher than 100 nmol/L ouabain also induced impairment of
      ABCC1 activity, increasing the accumulation of carboxyfluorescein diacetate, an
      ABCC1 fluorescent substrate. Because ouabain is now accepted as an endogenous
      hormone, our results suggest that ABCC1 is regulated by hormones related to body
      volume control, which may have implications for the treatment of hypertensive
      cancer patients. Moreover, providing ABCC1 is expressed in several other tissues,
      such as brain, testis, and the immune system, and is related to the transport of
      glutathione, it is possible that ouabain release may control a number of
      functions within these organs and tissues by modulating both the expression and
      the activity of ABCC1.

PMID- 17453353
TI  - Fenugreek seed (Trigonella foenum graecum) polyphenols inhibit ethanol-induced
      collagen and lipid accumulation in rat liver.
AB  - Chronic alcoholism is associated with fatty liver and fibrosis characterized by
      collagen accumulation. Seeds of fenugreek, an annual herb, are reported to
      possess hepatoprotective activity. The study aims to investigate the effects of
      fenugreek seed polyphenol extract (FPEt) on liver lipids and collagen in
      experimental hepatotoxic rats. Hepatotoxicity was induced in male albino Wistar
      rats by administrating ethanol (6 g/kg per day) for 30 days. Control rats were
      given isocaloric glucose solution. FPEt was co-administered with ethanol at a
      dose of 200 mg/kg per day for the next 30 days. Silymarin was used as a positive
      control. Ethanol treatment caused increase in plasma and liver lipids, together
      with alterations in collagen content and properties. Administration of FPEt to
      alcohol-fed rats significantly improved lipid profile and reduced collagen
      content, crosslinking, aldehyde content and peroxidation. The effects were
      comparable with that of silymarin. FPEt administration had a positive influence
      on both lipid profile and on the quantitative and qualitative properties of
      collagen in alcoholic liver disease. The protective effect is presumably due to
      the bioactive phytochemicals in fenugreek seeds.

PMID- 17453354
TI  - Tuberculous lymphadenitis in patients undergoing continuous ambulatory peritoneal
      dialysis.
AB  - The aim of this study was to review the clinical features of tuberculous (TB)
      lymphadenitis in patients undergoing continuous ambulatory peritoneal dialysis
      (CAPD). Nine cases of TB lymphadenitis were diagnosed among 910 patients over a
      period of 10 years. There were five men and four women with a mean age of 51 +/-
      15.5 years. The TB lymphadenitis involved the cervical lymph nodes in six
      patients, supraclavicular lymph nodes in two patients and mediastinal lymph nodes
      in one patient. Six patients presented with clinically enlarged lymph nodes of
      whom four also had fever. Three other patients were incidentally found to have
      enlarged lymph nodes on routine chest X-ray or ultrasound examination of the
      neck. Diagnosis of TB lymphadenitis was made by demonstrating caseating
      granulomata with or without positive acid-fast bacilli on excisional lymph node
      biopsy. All patients were cured with standard anti-tuberculosis drugs for 12
      months. No recurrence of the TB lymphadenitis was observed after a mean follow-up
      of 59 +/- 30 months. We conclude that TB lymphadenitis is not uncommon among
      patients on CAPD. A high index of suspicion is needed for early diagnosis of this
      condition. Prompt initiation of anti-tuberculosis treatment is associated with
      good prognosis.

PMID- 17453355
TI  - Age-related change of endocytic receptors megalin and cubilin in the kidney in
      rats.
AB  - Megalin and cubilin are the major endocytic receptors responsible for resorption
      of glomerular filtrate proteins, particularly albumin, in the renal proximal
      tubule. In order to better understand the mechanism of the development of
      albuminuria with age in rats, we investigated age-related change of the amount
      and cellular localization of both receptors in the kidney. Immunoblot analysis of
      the kidney extracts showed that the amount of megalin significantly decreased
      with age. Although there was no age-related change in the amount of intact
      cubilin, the amount of cubilin fragments increased with age. Immunohistochemical
      study revealed that megalin and cubilin were predominantly localized in brush
      border membrane of proximal tubular cells in young rats, but the receptors tended
      to diffuse into the cytoplasm in the old rats. Interestingly, low but significant
      amounts of megalin and cubilin were present in the glomerular cells in addition
      to the proximal tubular cells. The quantity of receptors progressively increased
      in the glomerulus with age. This age-related increase might be to compensate for
      the age-related defect of the uptake of albumin by the proximal tubules. Thus,
      although it is unclear whether megalin and cubilin in the glomerulus contribute
      to the uptake of albumin in primary urine, the age-related increase in the amount
      of albumin in urine might at least partly be due to quantitative and qualitative
      alterations of both receptors in the proximal tubule.

PMID- 17453356
TI  - Quantity and quality of potential drug interactions with coumarin anticoagulants
      in the Netherlands.
AB  - OBJECTIVE: Coumarin anticoagulants are prone to potentially life-threatening drug
      drug interactions due to a combination of unfavorable properties. However, real
      life data on the actual occurrence are scarce. The aim of this study was to
      quantify and qualify potential drug interactions with coumarin anticoagulants in
      daily practice. METHODS: A cohort study including all users of phenprocoumon or
      acenocoumarol during the period 1991-2003 in the PHARMO Record Linkage System.
      All 24 individual drugs and 11 drug groups interacting with coumarins according
      to central database used in the Dutch pharmacies were considered. MAIN OUTCOME
      MEASURE: Frequency and type of potential drug interactions during anticoagulant
      therapy with coumarins. RESULTS: 48,627 out of 76,455 mainly acenocoumarol-users
      (64%) were dispensed at least one potentially interacting drug (PID) during
      anticoagulant therapy. About 35% of these cases were dispensed a (very) strongly
      interacting drug, whereas 3% were dispensed a contraindicated drug. Antibacterial
      drugs and NSAIDs (39% and 37% of all users, respectively) were the most
      frequently dispensed PIDs. CONCLUSION: Potential drug interactions with coumarins
      frequently occur in daily practice, confronting two-thirds of patients with an
      increased risk of bleeding. To a large part, this is attributable to commonly
      prescribed medication like antibacterial drugs and NSAIDs. This situation
      substantiates the need for proper monitoring or new anticoagulants with less drug
      drug interactions.

PMID- 17453357
TI  - Nocardiosis in a tertiary care hospital in North India and review of patients
      reported from India.
AB  - Nocardiosis, an uncommon infection of the past, is being increasingly reported in
      recent years with rise of immunosuppressed patients. In India, very few centers
      have reported this disease. The present report describes twelve consecutive cases
      of nocardiosis reported over a period of 26 months (January 2004 to March 2006)
      from a tertiary care center in north India. The patients were predominantly males
      (75%) with age range of 8-65 years and mean age of 38.4 years. Eleven patients
      had known underlying illness including renal transplantation, human
      immunodeficiency virus infection, and long-term steroid therapy. One patient with
      cerebral nocardiosis had no detectable predisposing factor. Infection involved
      central nervous system (3 cases), lungs (5 cases), subcutaneous tissue (1 case),
      and anterior mediastinum (1 case). Disseminated infection was documented in two
      patients. Nocardia asteroides complex was incriminated in six patients, N.
      brasiliensis in five and N. otitidiscaviarum in one patient. All the isolates
      were sensitive to co-trimoxazole, amikacin, cefotaxime and imipenem. Good
      therapeutic response was observed in 10 (90.9%) of 11 patients treated with
      antibiotics including co-trimaxazole, cephalosporins, amikacin, and imipenem
      alone or in combination. The series of nocardiosis reported from India has also
      been reviewed.

PMID- 17453359
TI  - Abstracts of the European Epidemiology Federation of the International
      Epidemiological Association (IEA-EEF) European Congress of Epidemiology 2006.
      June 28-July 1, 2006. Utrecht, The Netherlands.

PMID- 17453358
TI  - Incorporation of somatic BRAF mutation testing into an algorithm for the
      investigation of hereditary non-polyposis colorectal cancer.
AB  - Patients suspected on clinical grounds to have hereditary non-polyposis
      colorectal cancer (HNPCC) may be offered laboratory testing in order to confirm
      the diagnosis and to facilitate screening of pre-symptomatic family members.
      Tumours from an affected family member are usually pre-screened for
      microsatellite instability (MSI) and/or loss of immunohistochemical expression of
      mismatch repair (MMR) genes prior to germline MMR gene mutation testing. The
      efficiency of this triage process is compromised by the more frequent occurrence
      of sporadic colorectal cancer (CRC) showing high levels of MSI (MSI-H) due to
      epigenetic loss of MLH1 expression. Somatic BRAF mutations, most frequently
      V600E, have been described in a significant proportion of sporadic MSI-H CRC but
      not in HNPCC-associated cancers. BRAF mutation testing has therefore been
      proposed as a means to more definitively identify and exclude sporadic MSI-H CRC
      cases from germline MMR gene testing. However, the clinical validity and utility
      of this approach have not been previously evaluated in a familial cancer clinic
      setting. Testing for the V600E mutation was performed on MSI-H CRC samples from
      68 individuals referred for laboratory investigation of suspected HNPCC. The
      V600E mutation was identified in 17 of 40 (42%) tumours showing loss of MLH1
      protein expression by immunohistochemistry but in none of the 28 tumours that
      exhibited loss of MSH2 expression (P < 0.001). The assay was negative in all
      patients with an identified germline MMR gene mutation. Although biased by the
      fact that germline testing was not pursued beyond direct sequencing in many cases
      lacking a high clinical index of suspicion of HNPCC, BRAF V600E detection was
      therefore considered to be 100% specific and 48% sensitive in detecting sporadic
      MSI-H CRC amongst those cases showing loss of MLH1 protein expression, in a
      population of patients with MSI-H CRC and clinical features suggestive of HNPCC.
      Accordingly, we recommend the incorporation of BRAF V600E mutation testing into
      the laboratory algorithm for pre-screening patients with suspected HNPCC, whose
      CRCs show loss of expression of MLH1. In such tumours, the presence of a BRAF
      V600E mutation indicates the tumour is not related to HNPCC and that germline
      testing of MLH1 in that individual is not warranted. We also recommend that in
      families where the clinical suspicion of HNPCC is high, germline testing should
      not be performed on an individual whose CRC harbours a somatic BRAF mutation, as
      this may compromise identification of the familial mutation.

PMID- 17453361
TI  - Long-term follow-up of the randomized Stockholm trial on adjuvant tamoxifen among
      postmenopausal patients with early stage breast cancer.
AB  - The Stockholm Breast Cancer Study Group conducted a randomized trial during 1976
      through 1990 comparing adjuvant tamoxifen versus control. A total of 2,738
      postmenopausal women with invasive, early stage disease were randomised between
      tamoxifen for 2 or 5 years, or no adjuvant endocrine therapy. Among high-risk
      patients the treatment was given against a background of either postoperative,
      locoregional radiation or CMF-type chemotherapy. The median follow up was 18
      years (range 11-25 years). There was a statistically significant (p =0.001)
      interaction between ER status and tamoxifen with no treatment benefit among
      receptor negatives. PgR-status had little additional predictive value. Among ER
      positive patients tamoxifen reduced locoregional recurrences by 48%,
      contralateral breast cancers by 54%, distant metastases by 28%, and all events by
      24% (p <0.001). On the other hand, there was a substantial increase of
      endometrial cancer associated with tamoxifen. There was no effect of tamoxifen on
      intercurrent mortality whereas breast cancer deaths were reduced by 31% (p
      <0.001) and overall mortality by 15% (p =0.01). Tamoxifen produced long-term
      benefits among estrogen receptor positive patients in terms of breast cancer
      related events, but also an increased incidence of endometrial cancer. Despite
      long-term follow-up we observed no benefit with tamoxifen in terms of
      cardiovascular mortality.

PMID- 17453362
TI  - Cost-effectiveness of intensive adjuvant chemotherapy for high-risk breast
      cancer: is tailored and dose-escalated chemotherapy with growth factor support
      (GFS) more costly and less effective than marrow-supported high-dose chemotherapy
      - results from a randomized study.
AB  - Based on randomized studies bone-marrow supported (BMS) high-dose chemotherapy
      (HDCT) is not superior to conventional CT as adjuvant treatment for high-risk
      breast cancer. To compare the cost-effectiveness of these treatments we examined
      the data of Finnish patients in the SBG9401 trial 1. Patients were randomized to
      receive either dose-escalated (de FEC) (group A, n =59) or FEC and HDCT+BMS
      (group B, n =70). They received adjuvant radiotherapy (RT) + tamoxifen. All
      direct health care costs of first line treatment at the oncology units were
      considered as well as productivity costs within the first 3 years of follow-up.
      Effectiveness was measured by the number of survival days during 5 years of
      follow-up. The mean direct health care costs were significantly higher in group B
      (25829 euro in group A vs. 36605 euro in group B, p <0.001), mainly due to a
      higher number of hospital days. Half of the costs in group A was due to the use
      of filgrastim (15335 euro in A and 2969 euro in B, p <0.001). The costs of RT
      were only 5% of total costs. There was no statistically significant difference
      between the groups in the number of survival days, but sensitivity analysis based
      on bootstrapping suggested that treatment A would be a less costly and more
      effective alternative in a great majority of cases.

PMID- 17453363
TI  - Trastuzumab in adjuvant breast cancer therapy. A model based cost-effectiveness
      analysis.
AB  - Trastuzumab has shown activity in early breast cancer patients that overexpress
      HER2. Significant resources have to be allocated to finance this therapy,
      underlining the need for cost-effectiveness analysis. A model was set up,
      societal costs were calculated and the discount rate was 3%. Life expectancy data
      were based on the literature and prolonged according to qualified guess (10% and
      20% absolute improvement in overall survival (OS)). The comparator was the
      FEC(100) regimen. The median additional health care cost per patient treated was
      33,597 euros. The yielding cost per life year gained (LYG) was 15,341 euros with
      a 20% improved OS and 35,947 euros with 10% improved OS. The corresponding net
      health care cost per quality adjusted life year (QALY) was 19,176 euros and
      44,934 euros. Including all resource use the figures were 8148 euros and 30,290
      euros per LYG. Sensitivity analyses documented survival gain, price of
      trastuzumab, production gain and discount rate to be the major factors
      influencing cost-effectiveness ratio. Trastuzumab is indicated cost effective in
      Norway.

PMID- 17453364
TI  - Individually tailored toxicity-based 5-fluorouracil, epirubicin and
      cyclophosphamide (FEC) therapy of metastatic breast cancer.
AB  - Chemotherapy dosing only based on body surface area (BSA) results in marked
      pharmacokinetic and toxicity variations, which may result in an inferior outcome
      for some patients. A toxicity-based dosing schedule for individually tailored
      treatment with granulocyte colony-stimulating factor (G-CSF) supported 5
      fluorouracil (F), epirubicin (E) and cyclophosphamide (C) (dFEC) was developed
      and studied in patients with metastatic breast cancer with the purpose to
      determine its efficiency and toxicity. Twenty-six women, median age 48 years,
      were included and the individual E and C doses were tailored stepwise based on
      the recorded hematological toxicity. Twenty-one patients (81%; 95% confidence
      interval (CI), 66% to 96%) had an objective response, including six complete
      responses (23%; CI, 7%-39%). At median follow-up of 113 months, the median time
      to progression and median overall survival were 14 and 36 months, respectively.
      The delivered dose intensity was high but varied substantially between patients
      (ranges F 126-202, E 14.4-36.0, C 160-510 mg/m(2)/w). The dominating grade III/IV
      toxicity was nausea (12% of patients) and febrile neutropenia (31% of patients).
      The tailored and dose-escalated FEC was highly active and feasible in metastatic
      breast cancer and may provide a pragmatic way of overcoming the shortcomings of
      standard BSA-based dosing.

PMID- 17453365
TI  - Differences in outcome for positive margins in a large cohort of breast cancer
      patients treated with breast-conserving therapy.
AB  - A study of the possible difference in outcome for positive margins for invasive
      carcinoma (IC) versus ductal carcinoma in situ (DCIS), and with regard to
      different age categories in a large prospective cohort of patients with invasive
      breast cancer. A total of 2 291 BCT were analyzed. Margins were positive for IC
      in 8.7% and for DCIS in 4.6%. The median follow-up was 83 months. The 10-year
      local recurrence-free survival for negative margins vs. positive margins for IC
      vs. positive for DCIS for women < or = 40 years were 84.4% vs. 34.6% (HR 4.5) vs.
      67.5%, and for women >40 years 94.7% vs. 92.6% vs. 82.6% (HR4.2). The 10-year
      distant disease-free survival for negative margins vs. positive margins for IC
      vs. positive for DCIS women < or = 40 years were 72.0% vs. 39.7% (HR 3.4) vs.
      77.8%. The disease-specific survival showed a significant relation to positive
      margins for IC in young women. The effect of positive margin for IC seems to be
      limited to young women only, and is not only restricted to local control, but
      also to distant metastasis and survival. On the other hand a positive margin for
      DCIS is a risk factor for local control in women >40 years.

PMID- 17453366
TI  - Effect of a vigorous aerobic regimen on physical performance in breast cancer
      patients - a randomized controlled pilot trial.
AB  - This randomized, controlled pilot trial was carried out to assess the feasibility
      and efficacy of an aerobic exercise in enhancing physical performance of breast
      cancer patients after adjuvant treatments. The potential of the training regimen
      to prevent accompanying bone loss was also assessed. Thirty patients, 41-65 years
      of age, were randomly assigned into training or control groups shortly after
      adjuvant chemo- or radiotherapy. The 12-week training included a guided aerobic
      exercise session once a week (the effective part being either step aerobic- or
      circuit-training in alternate weeks) and similar home exercise sessions twice a
      week. Adherence to the guided sessions was 78%, while home training was performed
      an average 2.1 times per week. Agility assessed with figure-8 running test and
      peak jumping power showed significant between-group treatment-effects
      (approximately 5% and approximately 10%, respectively). Judged from the
      accelerometer data, reaction forces up to six times body weight occurred during
      the training, which implies that the training could also have potential to affect
      bone mass. The present exercise regimen turned out to be feasible and effective
      among breast cancer patients in terms of physical performance. Large controlled
      trials are necessary to confirm these findings.

PMID- 17453367
TI  - Quantitative assessment of lung density changes after 3-D radiotherapy for breast
      cancer.
AB  - Our aim was to reduce the rates of clinical and radiological pneumonitis in local
      regional radiotherapy (RT) for breast cancer compared to a previous treatment
      series by applying a pre-planned lung dose volume constraint. 3-D dose planning
      was performed in 66 women with the aim of not exceeding an ipsilateral V20 of
      30%. The patients were followed for short-term signs/symptoms of post-RT
      pneumonitis and radiological changes on chest CT 4 months after RT. Radiological
      abnormalities were scored with a CT-adapted modification of a semi-quantitative
      classification system originally proposed by Arriagada which accounts for
      severity and affected lung regions. The abnormal subvolumes were contoured and
      the mean doses were calculated. Three cases of mild and one case of moderate
      symptomatic pneumonitis were diagnosed. The mean V20 was higher in symptomatic
      than in unaffected patients, 29% vs. 24% (p =0.04). Mild/moderate radiological
      changes were frequently observed on CT in regions with average doses >30 Gy.
      According to multivariate modeling, a trend for association was found between the
      studied dosimetric factors V13, V20, V30 and mean lung dose, and moderate-severe
      changes on CT but not with patient specific covariates, e.g. chemotherapy or
      tamoxifen exposure. 3-D planned local-regional RT with a preplanned lung dose
      volume constraint of V20 <30% resulted in few cases of moderate symptomatic
      pneumonitis. Mild/moderate radiological changes were still detectable on CT in
      subvolumes receiving doses >30 Gy. Long-term follow-up for evaluation of possible
      late morbidity is warranted.

PMID- 17453368
TI  - Hormone therapy and estrogen receptor expression in breast cancer.
AB  - Postmenopausal hormone therapy (HT) may increase breast cancer risk and influence
      tumor characteristics. We investigated 321 postmenopausal women aged 50-65 years,
      with breast cancer, diagnosed and treated at Radiumhemmet, Karolinska Hospital,
      during 1993-1997. In women using HT (n =90) estrogen receptor concentration (ER)
      at diagnosis were lower than in non-users (n =135) (1.17 vs 1.70 fmol/microg; p
      <0.05). HT users also had a tendency to less multifocal (5 vs 12%) (p <0.05) and
      metastatic disease (5% vs 2%) however this was not statistically significant. The
      estrogen receptor expression is always considered in the judgement on hormone
      dependency and the clinical decision on adjuvant endocrine therapy. A suppression
      of ER during HT could tentatively influence the treatment decisions in breast
      cancer patients and maybe disregard patients from endocrine treatment.

PMID- 17453369
TI  - Amplification of TOP2A and HER-2 genes in breast cancers occurring in patients
      harbouring BRCA1 germline mutations.
AB  - BRCA1 associated tumours are found to express an oestrogen receptor negative
      "basal epithelial-like" phenotype. In contrast to ER negative tumours in general,
      such tumours rarely harbour amplification of the HER-2 gene. However, little is
      known about TOP2A gene amplification status in BRCA1-associated tumours. Such
      information may be of importance to therapy, as amplification of TOP2A has been
      associated with dose-dependent sensitivity to anthracycline therapy in breast
      cancer. We examined 40 breast carcinomas from BRCA1 mutation carriers and 40
      sporadic breast carcinomas matched for age, tumour diameter and histological
      grade for HER-2 and TOP2A amplification status using fluorescence in situ
      hybridisation (FISH). Co-amplification of TOP2A and HER-2 was found in four of
      the mutation carriers and in three of the controls. While six tumours in the
      control group harboured HER-2 amplifications with normal TOP2A, this occurred in
      three of the BRCA1 associated tumours only. In contrast, three of the BRCA1
      associated tumours but none of the controls harboured TOP2A amplification despite
      normal HER-2 status. Our findings have potential therapeutic implications. HER-2
      assessment is routinely used to select breast cancer patients for trastuzumab but
      also dose-intensive anthracycline therapy. Our data suggest that BRCA1-associated
      breast cancers also need to be tested for TOP2A amplification.

PMID- 17453370
TI  - Oestrogen and progesterone receptor status of individual foci in multifocal
      invasive ductal breast cancer.
AB  - Widespread acceptance of breast conserving surgery for early breast cancer has
      led to renewed interest in multifocality, which is seen in 13-63% of breast
      cancers. According to current guidelines, oestrogen/progesterone receptor status
      is assessed on the sample obtained at initial core biopsy or the main tumour
      focus in multifocal breast cancer (more than one distinct tumour focus in a
      quadrant). We assessed receptor status of individual foci in multifocal breast
      cancer. Mastectomy specimens for 18 cases of multifocal breast cancer were
      identified. Immunohistochemical staining for oestrogen and progesterone receptors
      was performed on all tumour foci. On histological examination 11 patients
      demonstrated two independent tumour foci, three demonstrated three foci and four
      demonstrated four foci. Minor differences in oestrogen receptor score were seen
      between foci (attributed to the subjective nature of the scoring system), which
      did not affect the overall positive/negative classification. Sixteen patients
      (88%) were oestrogen receptor-positive. Progesterone receptor staining showed
      more variability between foci in two patients but, since the tumours were
      oestrogen receptor-positive this would not have affected clinical decision
      making. No major differences in oestrogen receptor status between multiple tumour
      foci in the same quadrant were found in this pilot study.

PMID- 17453371
TI  - Phase II trial of pegylated liposomal doxorubicin (Caelyx) plus Gemcitabine in
      chemotherapeutically pretreated patients with advanced breast cancer.
AB  - A phase II trial was performed to investigate the efficacy and tolerance of
      combined gemcitabine and liposomal doxorubicin +/- recombinant human granulocyte
      colony-stimulating factor (G-CSF) in patients with chemotherapeutically
      pretreated metastatic breast cancer. Thirty-four patients were entered in this
      trial. Chemotherapy consisted of gemcitabine and liposomal doxorubicin +/- G-CSF.
      Twenty seven patients received this regimen as 2nd line therapy, five patients as
      3rd line and two patients as 4th line therapy after having failed taxane- and/or
      anthracycline-based chemotherapy or other drug combinations. After a median of
      six courses, an overall response rate of 26% (9 PR in 34 enrolled patients) was
      observed; 14 patients had disease stabilization (41%), and eight (24%)
      progressed. Three patients were not evaluable for response due to anaphylaxis
      after the first course and protracted thrombocytopenia. The median TTP was 7.5
      months, and median overall survival was 15 months. Myelosuppression was the most
      frequently observed toxicity. Non-haematological side effects were generally mild
      to moderate. Our data suggest that gemcitabine and liposomal doxorubicin +/- G
      CSF is an effective and fairly well tolerated regimen for chemotherapeutically
      pretreated patients with advanced breast cancer.

PMID- 17453372
TI  - Nasopharyngeal carcinoma. Treatment planning with IMRT and 3D conformal
      radiotherapy.
AB  - The study was undertaken in order to compare dose plans for intensity-modulated
      radiotherapy (IMRT) with 3D conformal radiotherapy (3D-CRT) dose plans in
      patients with nasopharyngeal carcinoma (NPC). Clinical data from 20 consecutive
      patients treated with IMRT are presented. For 11 patients 3D-CRT plans were made
      and compared to the IMRT plans with respect to doses to the planning target
      volumes (PTVs) and to organs at risk (OARs). For comparison of the conformation
      of dose to defined target volumes the conformity index (CI) was used. Target
      volume coverage and critical organ protection were significantly improved with
      IMRT compared to 3D-CRT. One-year loco-regional control, distant metastasis-free
      survival, and overall survival were 79%, 72%, and 80%. Two patients have had
      recurrence in the clinical target volume (CTV) only and seven patients have
      relapsed in distant organs and/or in head-and-neck areas outside the target
      areas. The study confirms that IMRT is superior to 3D-CRT in the treatment of
      NPC. As locoregional control of NPC improves we are facing an increasing number
      of recurrences outside the irradiated area.

PMID- 17453373
TI  - Abnormal bone remodeling process is due to an imbalance in the receptor activator
      of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) axis in patients
      with solid tumors metastatic to the skeleton.
AB  - The role of receptor activator of nuclear factor-kappaB ligand
      (RANKL)/osteoprotegerin (OPG) system, and osteopontin (OPN) was studied in
      patients with solid tumors metastatic to the bone in relation to the type of
      malignancy and the neoplastic burden to the skeleton. Levels of soluble RANKL
      (sRANKL), OPG and OPN were assessed in 61 patients with breast, lung and prostate
      cancer with newly-diagnosed metastasis to the bone, in parallel with bone
      resorption [C-telopeptide of type-I collagen (CTX), tartrate-resistant acid
      phosphatase-5b (TRACP-5b)] and bone formation markers [bone-alkaline phosphatase
      (bALP), osteocalcin (OC), and C-terminal propeptide of collagen type-I (CICP)].
      Patients had elevated serum levels of sRANKL, OPG, OPN, TRACP-5b, and bALP, and
      reduced OC levels compared to controls. OPG correlated with the extent of
      metastatic bone burden. Patients with breast and lung cancer shared increased
      levels of sRANKL, OPG, and OPN whereas prostate cancer patients had elevated
      values of OPG and bALP only. These results suggest that patients with solid
      tumors metastatic to the bone have severe disruption of the sRANKL/OPG axis.
      Breast and lung cancer seem to exert their osteolytic action through upregulation
      of the sRANKL/OPG system and OPN, whereas prostate cancer seems to provoke
      profound elevation of OPG levels only, thus leading to increased osteoblastic
      activity.

PMID- 17453374
TI  - Efficacy of pegylated liposomal doxorubicin in patients with advanced
      hepatocellular carcinoma.
AB  - Presently, no effective systemic therapy is available for patients with advanced
      hepatocellular carcinoma (aHCC). We sought to determine whether systemic
      treatment with pegylated liposomal doxorubicin (PLD) would yield a response rate
      of 20% in chemotherapy naive patients with aHCC. The study was designed according
      to the phase II Gehan two-step procedure with a precision of 10%. Enrollment
      criteria included histological diagnosis and radiological documentation of
      unresectable/metastatic HCC, WHO PS 0-2, relatively normal organ function, life
      expectancy greater than three months, lack of cardiomyopathy and active cardiac
      disease NYHA > or = II. PLD (40 mg/m(2) IV 1h-infusion) was administered on d1 q
      4 wk and response to treatment was evaluated radiologically every 3rd cycle (WHO
      criteria). Secondary endpoints included overall (OS) and progression free
      survival (PFS) and registration of toxicity. The median number of administered
      PLD cycles was 3. The best radiological response among the first 14 patients was
      1 PR, 5 SD, 3 PD, and 6 NE due to progressive disease clinically (Step 1). The
      15th patient did not respond to the PLD-therapy and the study was closed for
      accrual as the pre-planned analysis could be executed (Step 2). A response rate >
      or = 20% could be ruled out. The median PFS and OS survival was 82 days and 130
      days, respectively. Adverse events were generally mild in the subgroup of
      patients without signs of moderate hepatic failure at base line. Patients with
      WHO PS 2, liver tumour involvement >50%, bilirubin > or = 34 micromol/L, albumin
      <33 g/L, and/or Child Pugh B were unlikely to survive >90 days. PLD can be
      delivered safely in patients with aHCC and no signs of moderate hepatic failure.
      The therapy resulted, however, in few responses or cases of disease stabilization
      and has thus very limited activity in aHCC. Future studies on systemic
      chemotherapy should focus on patients without moderate hepatic failure, with WHO
      PS <2, and with liver tumour involvement <50%.

PMID- 17453375
TI  - Multi-centre phase II trial of Thalidomide in the treatment of unresectable
      hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is a hypervascular tumour, which overexpresses
      vascular endothelial growth factor. Thalidomide is an antiangiogenic agent with
      activity in refractory multiple myeloma. The purpose of this multi-centre phase
      II study was to evaluate the efficacy and toxicity of thalidomide in patients
      with advanced HCC. From February 2000 to November 2001, 37 patients with
      histologically proven, bi-dimensionally measurable advanced, unresectable HCC
      were enrolled. The starting dose of Thalidomide was 100 mg per day and escalated
      weekly by 100 mg to a maximum dose of 800 mg/day according to individual patient
      tolerance. Radiological tumour response and treatment related toxicities were
      prospectively assessed. Thirty-seven patients were evaluable for toxicity and 24
      patients were evaluable for response. The median Thalidomide dose was 400 mg/day.
      There was no complete response (CR). One patient had a radiological partial
      response (PR) (3%; 95% confidence interval [95% CI], 0% to 8%) and six (16%)
      patients had stable disease for more than 6 months. Somnolence and fatigue were
      the most common side effects, occurring in 84% and 73% of patients respectively.
      Thalidomide monotherapy is tolerable and associated with modest antitumour
      activity in advanced HCC.

PMID- 17453376
TI  - Demographic, clinical and treatment related predictors for event-free probability
      following low-dose radiotherapy for painful heel spurs - a retrospective
      multicenter study of 502 patients.
AB  - A total of 502 patients treated between 1990 and 2002 with low-dose radiotherapy
      (RT) for painful heel spurs were analysed for prognostic factors for long-term
      treatment success. The median follow-up was 26 months, ranging from 1 to 103
      months. Events were defined as (1) slightly improved or unchanged pain after
      therapy, or (2) recurrent pain sensations during the follow-up period. Overall 8
      year event-free probability was 60.9%. Event-free probabilities of patients with
      one/two series (414/88) were 69.7%/32.2% (p<0.001); >58/ < or = 58 years
      (236/266), 81.3%/47.9% (p=0.001); high voltage/orthovoltage (341/161),
      67.9%/60.6% (p=0.019); pain anamnesis < or = 6 months/ >6 months (308/194),
      76.3%/43.9% (p=0.001); single dose 0.5/1.0 Gy (100/401), 86.2%/55.1% (p=0.009);
      without/with prior treatment (121/381), 83.1%/54.9% (p=0.023); men/women
      (165/337), 61.2%/61.5% (p=0.059). The multivariate Cox regression analysis with
      inclusion of the number of treatment series, age, photon energy, pain history,
      single-dose and prior treatments revealed patients with only one treatment series
      (p<0.001), an age >58 years (p=0.011) and therapy with high voltage photons
      (p=0.050) to be significant prognostic factors for pain relief. Overall low-dose
      RT is a very effective treatment in painful heel spurs.

PMID- 17453377
TI  - Concomitant presentation of acute myeloid leukemia with T-cell large granular
      lymphocytic leukemia.
AB  - T-cell large granular lymphocyte leukemia (T-LGL) also known as T-cell chronic
      lymphocytic leukemia is rare and comprises a small minority of all small
      lymphocytic leukemias. The concomitant presentation of T-LGL with acute myeloid
      leukemia (AML) has not been previously reported. We present an elderly gentleman
      with concomitant T-LGL and AML (non-M3) diagnosed by a combination of morphologic
      evaluation, immunophenotyping by flow cytometry, and T-cell gene rearrangement
      studies. The patient was managed with combination AML chemotherapy. He remains
      alive and well seven months after initial diagnosis. A brief review of literature
      is also presented.

PMID- 17453378
TI  - Helical tomotherapy targeting total bone marrow - first clinical experience at
      the University of Minnesota.

PMID- 17453379
TI  - An inflammatory response with worsening of pleural effusion on treatment with
      erlotinib in non-small cell lung cancer.

PMID- 17453380
TI  - Aggressive osteoblastoma of clavicle a rare tumor at previously undescribed site.

PMID- 17453381
TI  - Effective combination therapy of bortezomib and dexamethasone for a plasma cell
      leukemia patient with multiple osteolytic lesions and extramedullary involvement.

PMID- 17453382
TI  - Schwannoma of tongue - a case report and short review of literature.

PMID- 17453386
TI  - Misconceptions about practicing evidence-based orthopedic surgery.

PMID- 17453387
TI  - "To whom do the results of this trial apply?" External validity of a randomized
      controlled trial involving 130 patients scheduled for primary total hip
      replacement.
AB  - BACKGROUND: Although the randomized controlled trial (RCT) is regarded as the
      gold standard for evaluation of the effect of an intervention, its external
      validity has been questioned. RCTs cannot be expected to produce results that are
      directly relevant to all patients and all settings, but they should at least
      allow patients and clinicians to judge to whom trial results can reasonably be
      applied. We assessed the external validity of an RCT investigating the efficacy
      of a fast-track program after total hip replacement. METHODS: 130 patients were
      identified as potential participants.18 patients were excluded, 33 enrolled
      patients declined to participate, and 79 patients were enrolled and randomized.
      We studied the distribution of preoperative characteristics and postoperative
      clinical variables in these 3 groups. RESULTS: A significant difference was found
      in both preoperative characteristics and clinical outcome variables. The non
      consenters were older, less healthy, and needed more help from the home care
      system. Furthermore, they were hospitalized longer and were more often
      transferred to a rehabilitation ward. INTERPRETATION: Our findings demonstrate
      the importance of patient inclusion criteria in RCTs. Moreover, they may account
      for the lack of reproducibility of RCT results in clinical practice dealing with
      fast-track programs.

PMID- 17453388
TI  - Bone grafting: historical and conceptual review, starting with an old manuscript
      by Vittorio Putti.
AB  - Vittorio Putti has been recognized as one of the founders of orthopedic science.
      He wrote a number of original papers on different topics from his vast experience
      of orthopedics. In a paper on bone grafting dated 1912, Putti demonstrated his
      modern way of thinking by his ability to study past experiences critically and by
      his willingness to compare his own experiences with those of other orthopedic
      surgeons. Putti's paper proposes principles that still apply today, and which can
      be considered as the basis of the modern science of grafting. The results of his
      work can be summarized as follows: a) The uniformity of bone graft integration
      processes, and a marked reduction in integration capacity in heteroplastic
      grafts. b) The osteogenetic incapability of the graft as opposed to the
      osteogenetic capability of the periosteum. c) Marked reduction in the biological
      capability of bone that has been treated with preservatives, boiled, or
      macerated. d) The importance of the quality of the tissues in which the bone
      graft is inserted, including the mechanical characteristics of the graft and its
      fixation. e) The importance of asepsis. f) The importance of functional exercise.
      These important experiences were achieved without Putti having any knowledge of
      immunology, vascular surgery, tissue preservation or non decalcified histology
      techniques.

PMID- 17453389
TI  - Viable cells survive in fresh frozen human bone allografts.
AB  - BACKGROUND: Fresh frozen bone allograft is available for human recipients after
      at least 6 months of quarantine at -80 degrees C. It is assumed that
      cryopreservation without cryoprotectant removes all viable donor cells. METHODS:
      We studied the in vitro cell growth from samples of fresh frozen human femoral
      head allografts after they had been released for patient use, and compared it
      with cell growth from a control group of fresh cancellous bone specimens from
      excised femoral heads (8 samples in each group). RESULTS: Cell outgrowths were
      seen in all of the fresh cancellous bone specimens (100% of replicates, 48
      replicates per specimen) but only in a small minority of replicates from 4 of the
      allograft samples (mean 3.1%). Reverse transcription quantitative polymerase
      chain reaction (RT-qPCR) investigations revealed that cell outgrowths from both
      groups contained mRNA for transcription factors Runx2 and Osterix, and also for
      matrix proteins collagen type I, osteocalcin and bone sialoprotein. This is
      consistent with the cells being osteoblast-related. INTERPRETATION: This study
      confirms that fresh frozen human bone allograft cells have the potential to grow
      in vitro, but the significance of this in recipients is currently unknown.

PMID- 17453390
TI  - Irradiation has no effect on the incorporation of impacted morselized bone: a
      bone chamber study in goats.
AB  - BACKGROUND: Gamma irradiation has been widely used for sterilization of bone
      allografts. However, gamma irradiation alters proteins. This is favorable when it
      reduces immunogenicity, but is undesirable when osteoinductive proteins are
      damaged. Although the effect of gamma irradiation on BMPs has been studied, the
      effect of irradiation on the process of incorporation of morselized bone chips
      remains unclear. We studied the effects of sterilization by gamma irradiation on
      the incorporation of impacted morselized allografts. METHODS: Bone chambers with
      impacted allografts, rinsed impacted allografts, allografts that were rinsed and
      subsequently irradiated, and an empty control were implanted in proximal medial
      tibiae of goats. Incorporation was evaluated using histology and
      histomorphometry. RESULTS: Histology revealed evidence of bone graft
      incorporation, which proceeded in a similar way in unprocessed, rinsed, and both
      rinsed and irradiated bone grafts. After 12 weeks, no difference in bone and
      tissue ingrowth was found between the unprocessed, the rinsed, and the rinsed and
      subsequently irradiated allografts. The amount of unresorbed graft remnant was
      highest in the unprocessed bone grafts. INTERPRETATION: We conclude that
      sterilization with gamma irradiation does not influence the incorporation of
      impacted rinsed bone allografts.

PMID- 17453391
TI  - Mice expressing a constitutively active PTH/PTHrP receptor in osteoblasts show
      reduced callus size but normal callus morphology during fracture healing.
AB  - BACKGROUND: The parathyroid hormone-/parathyroid hormone-related protein
      (PTH/PTHrP) receptor plays a crucial role in endochondral bone formation and
      possibly also in fracture healing. Patients with Jansen's metaphysial
      chondrodysplasia (JMC) have a gain-of-function mutation in the PTH/PTHrP
      receptor. Transgenic mice expressing JMC PTH/PTHrP receptor mutants in
      osteoblasts are characterized by increased trabecular bone formation and reduced
      osteoblastic activity at periosteal sites. We have analyzed the bone phenotype
      and studied the fracture healing process in this model. METHODS: We performed
      bone density analysis of tibiae from 17-week-old transgenic mice and controls.
      Also, tibial fractures were produced in 14-week-old mice. Fracture healing was
      examined by radiographic and histological analysis. RESULTS: Transgenic mice had
      a lower total bone mineral content (BMC), by a factor of one-third. The changes
      were bone compartment-specific with an increase in trabecular bone volume and a
      decrease in cortical thickness. The calluses in the transgenic mice were smaller,
      with a reduction in BMC and mean cross-sectional area by a factor of one-half.
      Despite the smaller size, however, the morphology and progression through the
      healing process were similar in both transgenic and wild-type littermates.
      INTERPRETATION: We conclude that the constitutively active PTH/PTHrP receptor has
      compartment-specific effects on bone formation when expressed in osteoblasts.
      During fracture healing, however, both the periosteal and the endochondral
      processes are activated, leading to fracture healing that is temporally and
      morphologically normal, although the callus tissue is less prominent.

PMID- 17453392
TI  - A novel rat model for the study of deficits in bone formation in type-2 diabetes.
AB  - BACKGROUND: There is evidence to suggest that impairment in bone formation and/or
      turnover is associated with the metabolic abnormalities characteristic of type-2
      diabetes mellitus. However, bone regeneration/repair in type-2 diabetes has not
      been modeled. Using Zucker Diabetic Fatty (ZDF) rats (a model of type-2 diabetes)
      for tibial distraction osteogenesis (DO), we hypothesized that bone formation
      within the distraction gap would be impaired. ANIMALS AND METHODS: Rats were
      examined for body weight, glycosuria, and glycosemia to confirm the diabetic
      condition during the study. The rats received placement of the external fixators
      and osteotomies on the left tibia. Distraction was initiated the following day at
      0.2 mm twice a day and continued for 14 days. The lengthened tibiae were
      harvested and distraction gaps were examined radiographically and histologically.
      RESULTS: We found significant reduction in new bone formation in the distraction
      gaps of the ZDF rats, both radiographically and histologically, compared to lean
      rats. We found a decrease in a marker of cellular proliferation in the
      distraction gaps and increased adipose volume in adjacent bone marrow of the ZDF
      rats. INTERPRETATION: Our findings suggest that this model might be used to study
      the contributions of leptin resistance, insulin resistance and/or hyperglycemia
      to impaired osteoblastogenesis in vivo.

PMID- 17453393
TI  - Blood flow and microdialysis in the human femoral head.
AB  - BACKGROUND: If it would be possible to detect lack of flow and/or the development
      of ischemia in bone, we might have a way of predicting whether a broken bone will
      heal. We established microdialysis (MD) and laser Doppler (LD) flow measurement
      in the human femoral head in order to be able to detect ischemia and measure
      changes in blood flow. MATERIAL AND METHODS: In 9 patients undergoing total hip
      arthroplasty for primary osteoarthrosis, two MD catheters were inserted into the
      femoral head through two drill holes after the blood flow had been visualized by
      LD. Then primary samples were collected with the femoral head in situ;
      thereafter, the head was removed and samples were collected over the following 4
      hours ex vivo. The variables obtained by MD were concentrations of glucose,
      lactate, pyruvate, and glycerol in extracellular fluid. RESULTS: The results
      showed development of ischemia with a statistically significant decrease in
      glucose concentration and elevation of the lactate/pyruvate ratio over time. The
      LD showed flow with the femoral head in situ and lack of flow when the femoral
      head was removed. INTERPRETATION: The use of MD was established in the human
      femoral head. Ischemic levels were detected within 2 h of cessation of blood flow
      in most patients.

PMID- 17453394
TI  - Local application of basic fibroblast growth factor increases the risk of local
      infection after trauma: an in-vitro and in-vivo study in rats.
AB  - INTRODUCTION: Local application of growth factors to stimulate wound and fracture
      healing is attracting increasing interest. We studied the effect of local
      application of a potent angiogenic growth factor, basic fibroblast growth factor
      (bFGF), on resistance to local infection after soft tissue trauma. METHODS: For
      in-vitro and in-vivo experiments, we used recombinant human bFGF. The in-vitro
      investigations were performed by isolation of human leukocyte fractions, cytokine
      analysis, phagocytosis assay, flow cytometry, and LDH assay. For the in-vivo
      investigation, a paired comparison of infection rates was carried out on Sprague
      Dawley rats after standardized, closed soft tissue trauma and local, percutaneous
      bacterial inoculation of different concentrations of Staphylococcus aureus (2 x
      10(4) to 2 x 10(7) colony-forming units (cfu)). The lower leg was treated with 1,
      10 or 100 ng bFGF (16 animals for each concentration) and without bFGF (16
      animals). RESULTS: Cytotoxic reactions due to the concentrations of bFGF used
      could be excluded in the in-vitro tests since incubations of isolated peripheral
      blood mononuclear cells (PBMCs) with increasing concentrations of bFGF for 24 h
      did not lead to an increase in the release of lactate dehydrogenase in the
      culture supernatants compared to corresponding control incubations without any
      bFGF added. A significant increase in cytokine release was observed after the co
      incubation of PBMCs with 100 or 200 ng of the same bFGF that was used for the
      animal experiments. Furthermore, the capacity of phagocytes in whole blood to
      phagocytose bacteria was suppressed in the presence of 100 ng exogenously added
      bFGF. We found continuously reduced granulocytic phagocytosis in FGF-supplemented
      blood compared to non-supplemented blood. In the in-vivo investigation, the
      infection rate for the group without bFGF was 0.25. In the groups with 1, 10 and
      100 ng bFGF, the infection rates were 0.5, 0.7 and 0.8, respectively. A dose
      dependent increase in infection rate was observed after local application of
      bFGF, compared to the untreated control group. The difference in infection rates
      for the groups in which 10 and 100 ng bFGF was used, relative to the group
      without bFGF, was statistically significant. INTERPRETATION: If these initial
      results are confirmed for other potent angiogenic growth factors, then the local
      use of growth factors for stimulation of wound and bone healing--a main focus of
      current research in traumatology--will have to be reconsidered and preceded with
      a strict evaluation of the risks and benefits.

PMID- 17453395
TI  - Preoperative gait analysis has a substantial effect on orthopedic decision making
      in children with cerebral palsy: comparison between clinical evaluation and gait
      analysis in 60 patients.
AB  - BACKGROUND: There is still some debate regarding the role of 3-dimensional gait
      analysis in routine preoperative evaluation of children with cerebral palsy. The
      aim of this prospective study was to evaluate to what extent introduction of 3-D
      gait analysis changes preoperative surgical planning. METHOD: Before gait
      analysis, 60 ambulatory children aged 10 (4-18) years with spastic cerebral palsy
      had a specific surgical plan outlined, based on clinical examination by
      orthopedic surgeons. After gait analysis, the proposed surgical procedures were
      reviewed to determine the frequency with which the treatment plans changed. A
      multidisciplinary team assessed the gait analysis. RESULTS: Treatment plans for
      42 of the 60 patients were altered after gait analysis. Surgical treatment was
      recommended for 49 patients whereas 11 were recommended non-surgical treatment.
      Of the 253 specific surgical procedures proposed, 97 procedures were not
      recommended after gait analysis and 65 additional procedures were recommended
      after the analysis. Thus, the number of procedures proposed was reduced by 13%. A
      total of 318 specific surgical procedures were proposed either clinically, by
      gait analysis, or both. There was overall agreement between the referring
      orthopedic surgeons and gait analysis in 156 of these 318 procedures (49%). Gait
      analysis proposed more surgery for psoas tenotomy and rectus femoris transfer,
      whereas less surgery was proposed for other soft tissue and bony procedures.
      There was good accordance between gait analysis recommendations and the surgery
      performed subsequently (92%). INTERPRETATION: Gait analysis provided important
      additional information that modified preoperative surgical planning to a high
      degree. The high accordance between recommendations and surgery performed
      suggests that surgeons seriously consider the gait data and treatment
      recommendations.

PMID- 17453396
TI  - Sonography after total hip replacement: reproducibility and normal values in 47
      clinically uncomplicated cases.
AB  - BACKGROUND AND PURPOSE: Interpretation of sonographic data is difficult when
      hematoma after total hip replacement is suspected, as there are no normative
      data. We describe the normal sonographic image, focusing on the amount and
      location of postoperative fluid collections after a clinically uncomplicated,
      primary total hip replacement by the posterior approach. Inter- and intraobserver
      reproducibility is also considered. PATIENTS AND METHODS: We performed sonography
      of the hip in 47 patients between the second and the fifth postoperative day.
      Bone-to-capsule distance and deep and superficial extraarticular fluid
      collections were measured. Intraclass correlation coefficients were calculated.
      RESULTS: The normal values of bone-to-capsule distance and amount of
      extraarticular fluid after total hip replacement were established from the upper
      bound of the 95% confidence interval. The upper bound for bone-capsule distance
      was 6 mm, for deep fluid collections 21 mm, and for superficial fluid collections
      28 mm. In this clinically normal patient group, 4 patients had an extreme value
      (< 3 SD) for bone-to-capsule distance. For the deep and superficial fluid
      collections, no extremes were found. No correlation was found between bone-to
      capsule distance and whether or not there was extraarticular fluid. Intraclass
      correlation coefficients were 0.98 for bone-to-capsule distance and 0.99 for
      fluid collection measurements. INTERPRETATION: Sonography is a reproducible
      method for the evaluation of fluid collections after total hip replacement. The
      values measured can be helpful in decision making when there is clinical
      suspicion of postoperative hematoma after hip replacement by the posterior
      approach.

PMID- 17453397
TI  - Minimally invasive anterolateral approach to the hip: risk to the superior
      gluteal nerve.
AB  - BACKGROUND: Minimally invasive approaches to the hip show promise of less muscle
      trauma compared to conventional approaches. What is the risk of damage to the
      superior gluteal nerve? We studied the course of the superior gluteal nerve.
      METHOD: 20 legs of 11 formalin-fixed Caucasian cadavers were dissected and the
      course and the distances of the superior gluteal nerve branches from the tip of
      the greater trochanter were documented. RESULTS: The branch of the gluteal
      superior nerve leading to the gluteal minimus muscle was 33 (20-50) mm from the
      tip of the greater trochanter, within a deeper layer. The nearest point of the
      superior gluteal nerve branches from the tip of the greater trochanter in the
      posterior region was 19 (10-30) mm, in the middle region 20 (20-30) mm and in the
      anterior region 20 (10-35) mm. In half of the cases, a distal intermuscular
      branch between gluteal medius and tensor fasciae latae muscle could be found,
      mean 27 (10-40) mm caudal and 38 (25-60) mm ventral to the tip of the greater
      trochanter. This distal branch is considered to create a loop with upper branches
      of the superior gluteal nerve within the tensor fasciae muscle. INTERPRETATION:
      The safe zone for the superior gluteal nerve was smaller than previously
      reported. Use of a minimal direct lateral approach puts the inferior branches
      within the gluteal medius at risk; however, a minimal anterolateral approach to
      the hip may compromise branches of the superior gluteal nerve to the tensor
      fasciae latae muscle.

PMID- 17453398
TI  - Similar effects of rofecoxib and indomethacin on the incidence of heterotopic
      ossification after hip arthroplasty.
AB  - BACKGROUND: Although indomethacin is effective in preventing heterotopic
      ossification (HO) after primary total hip arthroplasty, side effects are
      frequently observed. In the last decade a new class of drugs--the COX-2 selective
      nonsteroidal anti-inflammatory drugs--has been developed. To investigate the
      effect of these COX-2 selective NSAIDs on heterotopic ossification (HO) after
      primary total hip arthroplasty (THA), we conducted a randomized controlled trial
      using either indomethacin or rofecoxib for 7 days. METHODS: 186 patients received
      either indomethacin 3 times daily, or rofecoxib twice, and 1 placebo, daily for 7
      days. HO was graded according to the 1-year postoperative radiographs according
      to the Brooker classification. RESULTS: 12 of the 186 patients included
      discontinued their medication before the end of the trial due to side effects.
      The remaining 174 patients were included in the analysis. In the indomethacin
      group (n = 89), 77 patients (87%) showed no HO, 9 showed HO of grade 1 and 3
      showed HO of grade 2 according to the Brooker classification. In the rofecoxib
      group (n = 85) 73 patients (86%) showed no ossification, 9 showed grade 1, and 3
      showed grade 2. INTERPRETATION: The prophylactic effect of rofecoxib for 7 days
      in preventing heterotopic ossification after primary total hip arthroplasty is
      comparable to the effect of indomethacin given for 7 days. These results indicate
      that the development of HO follows a COX-2 pathway.

PMID- 17453399
TI  - Selective COX-2 inhibitor versus indomethacin for the prevention of heterotopic
      ossification after hip replacement: a double-blind randomized trial of 100
      patients with 1-year follow-up.
AB  - INTRODUCTION: Recent reports have suggested that selective COX-2 inhibition may
      be sufficient for the prevention of heterotopic ossification. METHODS: We
      performed a randomized controlled study to evaluate the effect of the selective
      COX-2 inhibitor rofecoxib compared to that of indomethacin on the incidence and
      extent of heterotopic ossification in patients who had undergone hip replacement
      surgery. 50 patients received a daily dose of 25 mg rofecoxib and 50 patients
      received a daily dose of 100 mg indomethacin (25, 25, and 50 mg). RESULTS: No
      ossifications were found in 48 patients. Grade-II ossifications were seen in 5/46
      patients in the rofecoxib group and in 6/50 patients in the indomethacin group.
      Grade-III and grade-IV ossifications were seen in 3/46 patients in the rofecoxib
      group only. The differences were not statistically significant. The study
      medication had to be discontinued in 2 patients in the indomethacin group, due to
      dyspepsia. INTERPRETATION: After short-term administration, the selective COX-2
      inhibitor rofecoxib was effective in preventing heterotopic ossification after
      total hip arthroplasty.

PMID- 17453400
TI  - The effect of middle-age body weight and physical activity on the risk of early
      revision hip arthroplasty: a cohort study of 1,535 individuals.
AB  - BACKGROUND: Overweight and a high level of physical activity are known risk
      factors for loosening of a total hip arthroplasty (THA) due to primary
      osteoarthritis. We wanted to investigate how these factors, together with age and
      sex, affect the risk of revision surgery. PATIENTS AND METHODS: We matched data
      from the Norwegian Arthroplasty Register with information on risk factors
      collected at a cardiovascular screening. We identified 1,535 primary THAs in the
      screened cohort (930 cemented implants using well-documented cement). Of the
      participants included, 969 were female. Mean age at screening was 49 years, at
      primary THA 63 years, and 69 years at the end of follow-up. We used Cox
      regression analysis to estimate relative risks (RRs). Event was defined as
      implant revision due to aseptic loosening of cup, stem or both. Follow-up was
      time from primary THA to event or censoring. RESULTS: Men were at greater risk
      than women of loosening of the femoral stem (RR 2.0, 95% CI 1.3-3.2). Both men
      and women with upper-quartile body weight were at increased risk of revision due
      to loosening of the stem (RR 2.5 and 2.7, respectively). Men with a high level of
      physical activity during leisure time were at increased risk of revision due to
      loosening of the cup (RR 4.8, 95% CI 1.3-18). In the multivariate model with
      adjustment for activity, there was little association between age at primary THA
      and risk of revision due to loosening. INTERPRETATION: We found that body weight
      and physical activity recorded long before THA affected the survival of total hip
      arthroplasties. Controlling for these variables weakened the association between
      age at primary surgery and aseptic loosening. Men had an increased risk of
      loosening of the femoral stem, also after controlling for lifestyle factors.

PMID- 17453401
TI  - Effectiveness of hip or knee replacement surgery in terms of quality-adjusted
      life years and costs.
AB  - BACKGROUND: Concurrent head-to-head comparisons of healthcare interventions
      regarding cost-utility are rare. The concept of favorable cost-effectiveness of
      total hip or knee arthroplasty is thus inadequately verified. PATIENTS AND
      METHODS: In a trial involving several thousand patients from 10 medical
      specialties, 223 patients who were enrolled for hip or knee replacement surgery
      were asked to fill in the 15D health-related quality of life (HRQoL) survey
      before and after operation. RESULTS: Mean (SD) HRQoL score (on a 0-1 scale)
      increased in primary hip replacement patients (n = 96) from 0.81 (0.084)
      preoperatively to 0.86 (0.12) at 12 months (p < 0.001). In revision hip
      replacement (n = 24) the corresponding scores were 0.81 (0.086) and 0.82 (0.097)
      respectively (p = 0.4), and in knee replacement (n = 103) the scores were 0.81
      (0.093) and 0.84 (0.11) respectively (p < 0.001). Of 15 health dimensions, there
      were statistically significant improvements in moving, usual activities,
      discomfort and symptoms, distress, and vitality in both primary replacement
      groups. Mean cost per quality-adjusted life year (QALY) gained during a 1-year
      period was euro 6,710 for primary hip replacement, euro 52,274 for revision hip
      replacement, and euro 13,995 for primary knee replacement. INTERPRETATION: Hip
      and knee replacement both improve HRQoL. The cost per QALY gained from knee
      replacement is twice that gained from hip replacement.

PMID- 17453402
TI  - Effect of bone marrow grafting on the titanium porous-coated implant in bilateral
      total knee arthroplasty.
AB  - BACKGROUND AND PURPOSE: Poor bone ingrowth into the porous coating of tibial
      components has been reported. We hypothesized that iliac marrow grafting might be
      useful to enhance bone ingrowth into a porous-coated implant. The first part of
      this study was to examine the presence of fibroblast colony-forming units (CFUF)
      containing osteogenic precursor cells in tibial bone marrow and iliac bone
      marrow. The second aim was to compare the clinical and radiographic results after
      bilateral total knee arthroplasty (TKA) with and without autologous bone marrow
      transplantation to the bone-implant interface. METHODS: Simultaneous bilateral
      TKA was performed in 21 patients with osteoarthritis. Aspirated iliac bone marrow
      was transplanted to the interface of one randomly selected porous-coated tibial
      component in each patient, and contralateral knees served as controls. All of the
      21 patients were followed for 5 years. RESULTS: The average number of CFU-F was
      significantly lower in tibial marrow than in iliac marrow (p = 0.008). The final
      fluoroscopically-guided radiographs revealed a decrease in the number of knees
      with radiolucent lines after marrow grafting compared to those without grafting
      (p = 0.004). INTERPRETATION: Iliac bone marrow is useful as a bone grafting
      material to enhance the biological fixation in porous-coated implants.

PMID- 17453403
TI  - The trochlea is medialized by total knee arthroplasty: an intraoperative
      assessment in 61 patients.
AB  - BACKGROUND: A medialization of the femoral component in a total knee arthroplasty
      (TKA) causes abnormal patellar tracking, which could result in patellar
      instability, pain, wear, and failure. Previous reports defined medialization in
      relation to the neutral position of the femoral component, but omitted to compare
      it to the anatomical position of the trochlea. We assessed intraoperatively
      whether there is a systematic error of the position of the prosthetic groove
      relative to the anatomical trochlea. MATERIAL AND METHODS: A special instrument
      was developed to measure consecutively the mediolateral position of the
      anatomical trochlea and the mediolateral position of the prosthetic groove. 3
      experienced knee surgeons determined the mediolateral error of the prosthetic
      groove in primary TKAs in 61 patients. RESULTS: There was a significant medial
      error of the prosthetic groove relative to the preoperative position of the
      trochlea, with a mean medial error of 2.5 mm (SD 3.3) INTERPRETATION: Our
      findings indicate that the trochlea is medialized by TKA. Because a conscious
      medialization of the femoral component in a TKA produces abnormal patellar
      tracking patterns, further investigations will be needed to analyze the clinical
      consequences of this medialization of the trochlea.

PMID- 17453404
TI  - Unicondylar knee replacement for primary osteoarthritis: a prospective follow-up
      study of 1,819 patients from the Finnish Arthroplasty Register.
AB  - BACKGROUND: The choice and use of unicondylar knee arthroplasty (UKA) has gone
      through a nation wide resurgence at the start of the 21st century in Finland. We
      evaluated the population-based survival of UKA in patients with primary
      osteoarthritis (OA) in Finland, and the factors affecting their survival. METHOD:
      The Finnish Arthroplasty Register was established in 1980. During the years 1985
      2003, 1,928 primary UKAs were recorded in the register; 1,819 of these were
      performed for primary OA. Of these 1,819 UKAs, we selected for further analysis
      implants that had been used in more than 100 operations during the study period.
      The survival rates of UKAs were analyzed using Kaplan-Meier analysis and the Cox
      regression model. RESULTS: Analysis of the whole study period showed that UKAs
      had a 73% (95% CI: 70-76) survival rate at 10 years, with revision for any reason
      as the end point. Those patients who received the Oxford menisceal bearing
      unicondylar (n = 1145) had a survival rate of 81% (95% CI: 72-89) at 10 years.
      The group that received the Miller-Galante II unicondylar (n = 330) had a 79%
      survival rate (95% CI: 71-87) at 10 years, whereas the Duracon (n = 196) had a
      survival rate of 78% (95% CI: 72-84) and the PCA (n = 146) had a survival rate of
      53% (95% CI: 45-60) at 10 years. The number of UKA operations in Finland has
      increased markedly in recent years. At the time of operation, the mean age of the
      patients was 65 (38-91) years. Younger patients (<or= 65 years of age) were found
      to have a 1.5-fold (95% CI: 1.1-2.0; p = 0.04) increased risk of revision
      compared to older patients (< 65 years). INTERPRETATION: UKA is a viable option
      for the treatment of unicompartmental osteoarthritis of the knee. However,
      patients should be made aware of the lower survival of the UKAs compared with
      total knee arthroplasties.

PMID- 17453405
TI  - Chronic compartment syndrome also affects nonathletic subjects: a prospective
      study of 63 cases with exercise-induced lower leg pain.
AB  - BACKGROUND: Chronic exertional compartment syndrome is most often reported in
      young and physically active people. PATIENTS AND METHODS: We studied 73
      consecutive patients (mean age 39 (16-77) years, 45 women) with a history of
      exercise-induced pain and suspicion of chronic exertional compartment syndrome
      (CECS) of the lower leg--clinically, radiographically and with intramuscular
      pressure measurements. RESULTS: Intramuscular pressure increased with
      reproduction of symptoms and fulfilled the criteria for diagnosis of CECS in 36
      patients (mean age 36 (16-65) years, 22 women), with engagement of 66 anterior, 2
      lateral and 7 posterior muscle compartments in 72 legs. The patients with CECS of
      the lower leg were divided into 4 etiological groups: 18 with overuse, 10 with
      earlier trauma, 4 insulin-treated diabetics, and 4 others. Two-thirds of the
      patients had pain during walking. The outcome after fasciotomy was excellent or
      good in 41/57 of the legs. INTERPRETATION: CECS of the lower leg probably has a
      multifactorial etiology and is more common in sedentary individuals than has been
      recognized previously. Fasciotomy appears to be beneficial in these cases also.

PMID- 17453406
TI  - Compression-locked nailing of the humerus: a mechanical analysis.
AB  - BACKGROUND: In the treatment of humeral fractures, reamed nailing and compression
      have been reported to give higher stability. In this cadaver study, we compared
      the Unreamed Humeral Nail (UHN) with the (reamed) Telescopic Locking Nail (TLN)
      to find out whether any differences exist concerning bending and rotational
      stability, both with and without compression. METHODS: Nails were tested in a
      paired set-up with 8 pairs of fresh frozen cadaveric humeri. The nail-bone
      constructs were submitted to axial distraction to test compression, four-point
      bending and torsion. After creating a bone defect simulating an unstable
      fracture, bending and torsional tests were run again RESULTS: After cyclic
      loading, distraction under compression with the TLN was significantly less than
      with the UHN: 0.10 (SD 0.06) vs. 0.31 (SD 0.18) mm (difference = -67%, 95% CI = 
      84% to -37%; p = 0.01). In bending, the constructs with TLN under compression
      were stiffer than those with the UHN: 0.96 (SD 0.25) vs. 0.80 (SD 0.25) kN/mm
      (difference = 0.16, 95% CI = 0.07 to 0.25; p = 0.01). In torsion and with a bone
      defect, no significant differences were found. INTERPRETATION: Both nails are
      capable of resisting physiological forces acting on the humerus. The constructs
      with the TLN under compression are more stable in bending. Compression with an
      axial set screw is the more stable option.

PMID- 17453407
TI  - Reconstruction of Mason type-III and type-IV radial head fractures with a new
      fixation device: 23 patients followed 1-4 years.
AB  - BACKGROUND: Treatment options in radial head fractures of Mason types III and IV
      range from open reduction and internal fixation (ORIF) to radial head resection
      with or without prosthetic replacement. PATIENTS: In a prospective study, the
      radiographic and clinical outcome was evaluated in 23 patients (age median 51
      years) with 23 complex radial head fractures median 2 (1-4) years after ORIF
      using a new fixation device (FFS; Orthofix). 14 Mason type-III fractures with 2
      concomitant olecranon fractures and 1 ulnar nerve lesion, and 11 type-IV
      fractures with 2 olecranon fractures and 2 fractures of the coronoid process were
      treated. 2 patients were lost to follow-up. In 7 cases of joint instability, an
      elbow fixator with motion capacity was applied after ORIF of the radial head.
      RESULTS: No radial head resection was necessary. No secondary dislocations or
      nonunion occurred. The Morrey elbow score was excellent in 8 and good in 4 Mason
      type-III fractures and excellent in 5, good in 3, and fair in 3 Mason type-IV
      fractures. INTERPRETATION: Reconstruction of comminuted radial head fractures can
      be performed with this device and radial head resection can be avoided.

PMID- 17453408
TI  - Use of a syringe as a drill sleeve for core decompression of the femoral head in
      osteonecrosis.

PMID- 17453409
TI  - Cholesterol depletion activates rapid internalization of submicron-sized
      acetylcholine receptor domains at the cell membrane.
AB  - Novel effects of cholesterol (Chol) on nicotinic acetylcholine receptor (AChR)
      cell-surface stability, internalization and function are reported. AChRs are
      shown to occur in the form of submicron-sized (240-280 nm) domains that remain
      stable at the cell-surface membrane of CHO-K1/A5 cells over a period of hours.
      Acute (30 min, 37 degrees C) exposure to methyl-beta-cyclodextrin (CDx), commonly
      used as a diagnostic tool of endocytic mechanisms, is shown here to enhance AChR
      internalization kinetics in the receptor-expressing clonal cell line. This
      treatment drastically reduced ( approximately 50%) the number of receptor domains
      by accelerating the rate of endocytosis (t(1/2) decreased from 1.5-0.5 h). In
      addition, Chol depletion produced ion channel gain-of-function of the remaining
      cell-surface AChR, whereas Chol enrichment had the opposite effect. Fluorescence
      measurements under conditions of direct excitation of the probe Laurdan and of
      Forster-type resonance energy transfer (FRET) using the intrinsic protein
      fluorescence as donor both indicated an increase in membrane fluidity in the bulk
      membrane and in the immediate environment of the AChR protein upon Chol
      depletion. Homeostatic control of Chol content at the plasmalemma may thus
      modulate cell-surface organization and stability of receptor domains, and fine
      tune receptor channel function to temporarily compensate for acute AChR loss from
      the cell surface.

PMID- 17453410
TI  - Apical phosphatidylserine externalization in auditory hair cells.
AB  - In hair cells of the inner ear, phosphatidylserine (PS), detected with
      fluorescent annexin V labeling, was rapidly exposed on the external leaflet of
      apical plasma membranes upon dissection of the organ of Corti. PS externalization
      was unchanged by caspase inhibition, suggesting that externalization did not
      portend apoptosis or necrosis. Consistent with that conclusion, mitochondrial
      membrane potential and hair-cell nuclear structure remained normal during
      externalization. PS externalization was triggered by forskolin, which raises
      cAMP, and blocked by inhibitors of adenylyl cyclase. Blocking Na(+) influx by
      inhibiting the mechanoelectrical transduction channels and P2X ATP channels also
      inhibited external PS externalization. Diminished PS externalization was also
      seen in cells exposed to LY 294002, which blocks membrane recycling in hair cells
      by inhibiting phosphatidylinositol 3-kinase. These results indicate that PS
      exposure on the external leaflet, presumably requiring vesicular transport,
      results from elevation of intracellular cAMP, which can be triggered by Na(+)
      entry into hair cells.

PMID- 17453411
TI  - Identification and characterization of autotransporter proteins of Yersinia
      pestis KIM.
AB  - Yersinia pestis is a Gram-negative bacterium that causes plague. Currently,
      plague is considered a re-emerging infectious disease and Y. pestis a potential
      bioterrorism agent. Autotransporters (ATs) are virulence proteins translocated by
      a variety of pathogenic Gram-negative bacteria across the cell envelope to the
      cell surface or extracellular environment. In this study, we screened the genome
      of Yersinia pestis KIM for AT genes whose expression might be relevant for the
      pathogenicity of this plague-causing organism. By in silico analyses, we
      identified ten putative AT genes in the genomic sequence of Y. pestis KIM; two of
      these genes are located within known pathogenicity islands. The expression of all
      ten putative AT genes in Y. pestis KIM was confirmed by RT-PCR. Five genes,
      designated yapA, yapC, yapG, yapK and yapN, were subsequently cloned and
      expressed in Escherichia coli K12 for protein secretion studies. Two forms of the
      YapA protein (130 kDa and 115 kDa) were found secreted into the culture medium.
      Protease cleavage at the C terminus of YapA released the protein from the cell
      surface. Outer membrane localization of YapC (65 kDa), YapG (100 kDa), YapK (130
      kDa), and YapN (60 kDa) was established by cell fractionation, and cell surface
      localization of YapC and YapN was demonstrated by protease accessibility
      experiments. In functional studies, YapN and YapK showed hemagglutination
      activity and YapC exhibited autoagglutination activity. Data reported here
      represent the first study on Y. pestis ATs.

PMID- 17453412
TI  - CLIC4 (p64H1) and its putative transmembrane domain form poorly selective, redox
      regulated ion channels.
AB  - Despite being synthesized in the cytosol without a leader sequence, the soluble
      253-residue mammalian protein CLIC4 (Chloride Intracellular Channel 4, or p64H1),
      a structural homologue of Omega-type glutathione-S-transferase, autoinserts into
      membranes to form an integral membrane protein with ion channel activity. A
      predicted transmembrane domain (TMD) near the N-terminus of CLIC4 could mediate
      membrane insertion, and contribute to oligomeric pores, with minimal
      reorganization of the soluble protein structure. We tested this idea by
      reconstituting recombinant CLIC4 in planar bilayers containing
      phosphatidyethanolamine, phosphatidylserine and cholesterol, recording ion
      channels with a maximum conductance of approximately 15 pS in KCl under both
      oxidizing and reducing conditions. The channels discriminated poorly between
      anions and cations, incompatible with the current "CLIC" nomenclature, and their
      conductance was modified by the trans (external or luminal) redox potential, as
      previously observed for CLIC1. We then reconstituted a truncated version of the
      protein, limited to the first 61 residues containing the predicted TMD. This
      included a single trans cysteine residue in the putative pore-forming subunits,
      at the external entrance to the pore. The truncated protein formed non-selective
      channels with a reduced conductance, but they retained their trans-redox
      sensitivity, and could still be blocked or inactivated by trans (not cis) thiol
      reative dithiobisnitrobenzoic acid. We suggest that oligomers containing the
      putative TMD are essential components of the CLIC4 pore. However, the pore is
      inherently non-selective, and any ionic selectivity in CLIC4 (and other membrane
      CLICs) may be attributable to other regions of the protein, including the channel
      vestibules.

PMID- 17453413
TI  - Cation coupling properties of human concentrative nucleoside transporters hCNT1,
      hCNT2 and hCNT3.
AB  - The SLC28 family of concentrative nucleoside transporter (CNT) proteins in
      mammalian cells contains members of two distinct phylogenic subfamilies. In
      humans, hCNT1 and hCNT2 belong to one subfamily, and hCNT3 to the other. All
      three CNTs mediate inwardly-directed Na(+)/nucleoside cotransport, and are either
      pyrimidine nucleoside-selective (hCNT1), purine nucleoside-selective (hCNT2), or
      broadly selective for both pyrimidine and purine nucleosides (hCNT3). While
      previous studies have characterized cation interactions with both hCNT1 and
      hCNT3, little is known about the corresponding properties of hCNT2. In the
      present study, heterologous expression in Xenopus oocytes in combination with
      radioisotope flux and electrophysiological techniques has allowed us to undertake
      a side-by-side comparison of hCNT2 with other hCNT family members. Apparent K
      (50) values for Na(+) activation were voltage-dependent, and similar in magnitude
      for all three transporters. Only hCNT3 was also able to couple transport of
      uridine to uptake of H(+). The Na(+)/nucleoside stoichiometry of hCNT2, as
      determined from both Hill coefficients and direct charge/flux measurements, was
      1:1. This result was the same as for hCNT1, but different from that of hCNT3
      (2:1). The charge-to-(22)Na(+) uptake stoichiometry was 1:1 for all three hCNTs.
      In parallel with their division into two separate CNT subfamilies, hCNT2 shares
      common cation specificity and coupling characteristics with hCNT1, which differ
      markedly from those of hCNT3.

PMID- 17453414
TI  - Effect of block deletions in the C-terminus on the functional expression of human
      anion exchanger 1 (AE1).
AB  - The human anion exchanger 1 (AE1) is the most abundant integral membrane protein
      in red cells and is responsible for the exchange of Cl(-) for HCO(3)(-). However,
      the detailed role played by the AE1 C-terminal region in the anion translocation
      and membrane trafficking process remains unclear. In this paper, we created four
      mutants in the human AE1 C-terminus by deletion of the residues Ala(891)
      Phe(895), Asp(896)-Glu(899), Asp(902)-Glu(906) and Val(907)-Val(911), to
      investigate the role of these sequences in functional expression of AE1. WT AE1
      and its deletion mutant constructs were expressed in HEK 293 cells. Western
      blotting showed that deletions of Ala(891)-Phe(895), Asp(896)-Glu(899), and
      Val(907)-Val(911) induced high expression of AE1, whereas loss of Asp(902)
      Glu(906) results in stable low expression. Pulse chase assays of WT AE1 and its
      mutants showed that the stability of protein is unaffected by the levels of
      expression of the AE1 and its mutants. Ala(891)-Phe(895), Asp(902)-Glu(906) and
      Val(907)-Val(911) mutants exhibited lower levels of trafficking to the plasma
      membrane compared with WT AE1, while the Asp(896)-Glu(899) mutant was more highly
      expressed at the plasma membrane. The decreased ability of the mutants to mediate
      Cl(-)/HCO(3)(-) exchange in transfected cells revealed that the deletion
      sequences have an important role in transport activity. These results demonstrate
      that the studied residues in the AE1 C-terminus differently affect the
      expression, membrane trafficking and functional folding of AE1.

PMID- 17453415
TI  - Topology and endoplasmic reticulum retention signals of the lysosomal storage
      disease-related membrane protein CLN6.
AB  - CLN6 is a polytopic membrane protein of unknown function resident in the
      endoplasmic reticulum (ER). Mutant CLN6 causes the lysosomal storage disorder
      neuronal ceroid lipofuscinosis. Defining the topology of CLN6, and the structural
      domains and motifs required for interaction with cytosolic and luminal proteins
      may allow insights into its function. In this study we analysed the topology, ER
      retention and oligomerization of CLN6. We demonstrated, by differential membrane
      permeabilization of transfected BHK cells using specific detergents and two
      distinct antibodies, that CLN6 contains an N-terminal cytoplasmic domain, seven
      transmembrane domains, and a luminal C terminus. Mutational analyses and confocal
      immunofluorescence microscopy showed that changes of potential ER localization
      signals in the N- or C-terminal domain (a triple arginine cluster, and a
      dileucine motif) did not alter the subcellular localization of CLN6. The deletion
      of a dilysine motif impaired partially the ER localization of CLN6. Furthermore,
      expression analyses of fusion and deletion constructs in non-neuronal and
      neuronal cells suggested that two portions of CLN6 contributed to its retention
      within the ER. We showed that the N-terminal domain was necessary but not
      sufficient for ER retention of CLN6 and that deletion of transmembrane domains 6
      and 7 was accompanied with the loss of ER localization and, in some instances,
      trafficking to the cisGolgi. From these data we concluded that CLN6 maintains its
      ER localization by expressing retention signals present in both the N-terminal
      cytosolic domain and in the carboxy-proximal transmembrane domains 6 and 7.
      Additionally, the ability of CLN6 to homodimerize may also prevent exit from the
      ER via an interaction with membrane-associated factors.

PMID- 17453416
TI  - The involvement of lipid rafts in epidermal growth factor-induced chemotaxis of
      breast cancer cells.
AB  - Metastasis is the major cause of morbidity and mortality in cancer. Recent
      studies reveal a role of chemotaxis in cancer cell metastasis. Epidermal growth
      factor receptors (EGFR) have potent chemotactic effects on human breast cancer
      cells. Lipid rafts, organized microdomain on plasma membranes, regulate the
      activation of many membrane receptors. In the current study, we investigated the
      role of lipid rafts in EGFR-mediated cancer cell chemotaxis. Our confocal
      microscopy results suggested that EGFR co-localized with GM1-positive rafts.
      Disrupting rafts with methyl-beta-cyclodextrin (mbetaCD) inhibited EGF-induced
      chemotaxis of human breast cancer cells. Supplementation with cholesterol
      reversed the inhibitory effects. Pretreatment with mbetaCD also impaired
      directional migration of cells in an in vitro "wound healing" assay, EGF-induced
      cell adhesion, actin polymerization, Akt phosphorylation and protein kinase Czeta
      (PKCzeta) translocation. Taken together, our study indicated that integrity of
      lipid rafts was critical in EGF-induced chemotaxis of human breast cancer cells.

PMID- 17453417
TI  - Self-aggregation--an intrinsic property of G(M1) in lipid bilayers.
AB  - We demonstrate that the ganglioside G(M1) in lipid bilayers of 1,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC) exhibits a non-uniform lateral distribution,
      i.e., enriched regions of GM(1) molecules are formed, which is an argument in
      favour of self-aggregation of G(M1) being an intrinsic property of G(M1)
      ganglioside. This was concluded from energy transfer/migration studies of BODIPY
      labelled gangliosides by means of time-resolved fluorescence lifetime and
      depolarization experiments. Three fluorophore-labelled gangliosides were
      synthesized to include either of two spectroscopically different BODIPY groups.
      These were specifically localized either in the polar headgroup region or in the
      non-polar region of the lipid bilayer. An eventual ganglioside-ganglioside
      affinity/aggregation induced by the BODIPY groups was experimentally excluded,
      which suggests their use in examining the influence of G(M1) in more complex
      systems.

PMID- 17453418
TI  - The oligomeric state of Derlin-1 is modulated by endoplasmic reticulum stress.
AB  - The endoplasmic reticulum (ER) is a major site of protein synthesis in
      eukaryotes. Newly synthesized proteins are monitored by a process of quality
      control, which removes misfolded or unassembled polypeptides from the ER for
      degradation by the proteasome. This requires the retrotranslocation of the
      misfolded proteins from the ER lumen into the cytosol via a pathway that, for
      some substrates, involves members of the recently discovered Derlin family. The
      Derlin-1 isoform is present as a dimer in the ER, and we now show that its
      dimerization is modulated by ER stress. Three distinct types of chemically
      induced ER stress substantially reduce the levels of Derlin-1 dimer as assayed by
      both cross-linking and co-immunoprecipitation. The potential function of the
      different Derlin-1 populations with respect to ER quality control is investigated
      by analysing their capacity to associate with a misfolded membrane protein
      fragment. We show for the first time that Derlin-1 can associate with an aberrant
      membrane protein fragment in the absence of the viral component US11, and
      conclude that it is the monomeric form of Derlin-1 that interacts with this
      potential ER-associated degradation substrate. On the basis of these data we
      propose a model where the pool of active Derlin-1 in the ER membrane can be
      modulated in response to ER stress.

PMID- 17453419
TI  - Lysenin-His, a sphingomyelin-recognizing toxin, requires tryptophan 20 for cation
      selective channel assembly but not for membrane binding.
AB  - Lysenin is 297 amino acid long toxin derived from the earthworm Eisenia foetida
      which specifically recognizes sphingomyelin and induces cell lysis. We
      synthesized lysenin gene supplemented with a polyhistidine tag, subcloned it into
      the pT7RS plasmid and the recombinant protein was produced in Escherichia coli.
      In order to obtain lysenin devoid of its lytic activity, the protein was mutated
      by substitution of tryptophan 20 by alanine. The recombinant mutant lysenin-His
      did not evoke cell lysis, although it retained the ability to specifically
      interact with sphingomyelin, as demonstrated by immunofluorescence microscopy and
      by dot blot lipid overlay and liposome binding assays. We found that the lytic
      activity of wild-type lysenin-His was correlated with the protein oligomerization
      during interaction with sphingomyelin-containing membranes and the amount of
      oligomers was increased with an elevation of sphingomyelin/lysenin ratio. Blue
      native gel electrophoresis indicated that trimers can be functional units of the
      protein, however, lysenin hexamers and nanomers were stabilized by chemical cross
      linking of the protein and by sodium dodecyl sulfate. When incorporated into
      planar lipid bilayers, wild type lysenin-His formed cation-selective channels in
      a sphingomyelin-dependent manner. We characterized the channel activity by
      establishing its various open/closed states. In contrast, the mutant lysenin-His
      did not form channels and its correct oligomerization was strongly impaired.
      Based on these results we suggest that lysenin oligomerizes upon interaction with
      sphingomyelin in the plasma membrane, forming cation-selective channels. Their
      activity disturbs the ion balance of the cell, leading eventually to cell lysis.

PMID- 17453420
TI  - Ion channels of glutamate receptors: structural modeling.
AB  - Ionotropic glutamate receptors belong to the superfamily of P-loop channels as
      well as K(+), Na(+), and Ca(2+) channels. However, the structural similarity
      between ion channels of the glutamate receptors and K(+) channels is a matter of
      discussion. The aim of this study was to analyze differences between the
      structures of K(+) channels and glutamate receptor channels. For this purpose,
      homology models of NMDA and AMPA receptor channels (M2 and M3 segments) were
      built using X-ray structures of K(+) channels as templates. The models were
      optimized and used to reproduce specific data on the structure of glutamate
      receptor channels. Particular attention was paid to the data of the binding of
      channel blockers and to the results of scanning mutagenesis. The modeling
      demonstrates that properties of glutamate receptor channel can be reproduced
      assuming only local structural deformations of the K(+) channel templates. The
      most valuable differences were found in the selectivity-filter region, whereas
      helical parts of M2 and M3 segments could have similar spatial organization with
      homologous segments in K(+) channels. It is concluded that the current
      experimental data on glutamate receptor channels does not reveal global
      structural differences with K(+) channels.

PMID- 17453421
TI  - Voltage-dependent anion channel (VDAC) participates in amyloid beta-induced
      toxicity and interacts with plasma membrane estrogen receptor alpha in septal and
      hippocampal neurons.
AB  - Voltage-dependent anion channel (VDAC) is a porin known by its role in metabolite
      transport across mitochondria and participation in apoptotic processes. Although
      traditionally accepted to be located within mitochondrial outer membrane, some
      data has also reported its presence at the plasma membrane level where it seems
      to participate in regulation of normal redox homeostasis and apoptosis. Here,
      exposure of septal SN56 and hippocampal HT22 cells to specific anti-VDAC
      antibodies prior to amyloid beta (Abeta) peptide was observed to prevent
      neurotoxicity. In these cell lines, we identified a VDAC form associated with the
      plasma membrane that seems to be particularly abundant in caveolae. The two
      membrane-related isoforms of estrogen receptor alpha (mERalpha) (80 and 67 kDa),
      known in SN56 cells to participate in estrogen-induced neuroprotection against
      Abeta injury, were also observed to be present in caveolae. Interestingly, we
      demonstrated for the first time that both VDAC and mERalpha interact at the
      plasma membrane of these neurons as well as in microsomal fractions of the
      corresponding murine septal and hippocampal tissues. These proteins were also
      shown to associate with caveolin-1, thereby corroborating their presence in
      caveolar microdomains. Taken together, these results suggest that VDAC-mERalpha
      association at the plasma membrane level may participate in the modulation of
      Abeta-induced cell death.

PMID- 17453422
TI  - The conserved carboxy-terminal region of the ammonia channel AmtB plays a
      critical role in channel function.
AB  - The ammonium transport (Amt) proteins are a highly conserved family of integral
      membrane proteins found in eubacteria, archaea, fungi and plants. Genetic,
      biochemical and bioinformatic analyses suggest that they have a common tertiary
      structure comprising eleven trans-membrane helices with an N-out, C-in topology.
      The cytoplasmic C-terminus is variable in length but includes a core region of
      some 22 residues with considerable sequence conservation. Previous studies have
      indicated that this C-terminus is not absolutely required for Amt activity but
      that mutations that alter C-terminal residues can have very marked effects. Using
      the Escherichia coli AmtB protein as a model system for Amt proteins, we have
      carried out an extensive site-directed mutagenesis study to investigate the
      possible role of this region of the protein. Our data indicate that nearly all
      mutations fall into two phenotypic classes that are best explained in terms of
      two distinct effects of the C-terminal region on AmtB activity. Residues within
      the C-terminus play a significant role in normal AmtB function and the C-terminal
      region might also mediate co-operativity between the three subunits of AmtB.

PMID- 17453423
TI  - Dental fluorosis in children in areas with fluoride-polluted air, high-fluoride
      water, and low-fluoride water as well as low-fluoride air: a study of deciduous
      and permanent teeth in the Shaanxi province, China.
AB  - OBJECTIVE: The aim of the study was to assess dental fluorosis (DF) in the
      deciduous and permanent teeth of children in areas with high-F coal (area A) and
      high-F water (area C) compared to children from area B, with low-F water and
      coal. MATERIAL AND METHODS: 596 children were examined. DF was assessed by TF
      score. F-content of indoor air, drinking water, coal, tea, rice, and maize was
      analyzed. RESULTS: F-content of air and coal ranged from 3.2 microg/m(3) and 25.8
      mg/kg (area B), 3.8 microg/m(3) and 36.3 mg/kg (area C) to 56.8 microg/m(3) and
      713.1 mg/kg (area A). Likewise, mean F-content of water ranged from approximately
      0.50 mg/l (areas A and B) to 3.64 mg/l (area C). F-content of tea leaves was
      similar in all three areas. Maize and rice contained <5 mg F/kg. Prevalence of
      primary teeth with DF was 49.1%, 2.0%, and 66.8% in areas A, B, and C,
      respectively. Similarly, DF was found in 96.7% (area A), 19.6% (area B), and
      94.4% (area C) of the permanent teeth. Severe fluorosis (TF > or = 5) was found
      in area A (47.0%) and area C (36.1%) (p<0.01). Early erupting teeth had slightly
      higher mean TF-scores in area A than in area C. CONCLUSIONS: DF was prevalent in
      both dentitions in areas A and C. Similarity in percentages of DF may indicate
      that indoor air with approximately 60 microg F/m(3) and drinking water with 3.6
      mg F/L are similarly toxic to developing permanent teeth. The percentage of
      deciduous teeth with DF was significantly lower in area A compared to area C.
      Where low-F coal and low-F water were used (area B), approximately 20% of
      permanent teeth had DF, indicating a relatively low tolerance to fluoride in
      Chinese children brought up under the present living conditions.

PMID- 17453424
TI  - Changes in caries experience among 35-year-old Oslo citizens, 1973-2003.
AB  - OBJECTIVE: The aims of the present study were to describe caries experience among
      35-year-olds in Oslo in 2003 and to assess changes in caries experience during
      the past 30 years using data from cross-sectional studies performed in 1973,
      1984, and 1993. MATERIAL AND METHODS: The dental status of 149 randomly selected
      35-year-olds in Oslo was examined in 2003 (response rate 64%) and the data were
      compared with available data from earlier studies. Dental caries was registered
      clinically and radiographically at the surface level, applying the same criteria
      as used in previous studies, and recorded as DMFS/T. RESULTS: The results
      indicate a gradual decrease in the mean DMFS scores by 62% from 68.2 in 1973 to
      26.1 in 2003. There was an 83% decrease in the mean number of DS, a 73% decrease
      in the mean number of MS, and a 56% decrease in the mean number of FS during this
      30-year period. The proportion of individuals with DS = 0 gradually increased
      from 5% in 1973 to 54% in 2003. There was also a significant decrease in the
      prevalence of recurrent caries from 2.8% in 1984 to 1.2% in 2003. While a
      statistically significant reduction in the number of decayed, missing, and filled
      surfaces was observed during the period 1984-1993, in the past decade (1993-2003)
      a significant decrease appeared only in the case of the filled surfaces.
      CONCLUSIONS: The results indicate that dental health among 35-year-olds in Oslo,
      measured as a reduction in caries experience, has improved substantially from
      1973 to 2003.

PMID- 17453425
TI  - Tooth loss in the elderly and its association with nutritional status, socio
      economic and lifestyle factors.
AB  - OBJECTIVE: Tooth loss impacts on general health and is a risk factor for
      malnutrition, disability, loss of self-sufficiency, and deterioration in quality
      of life. The present study was carried out to evaluate the prevalence of
      edentulism and its association with social and lifestyle factors in a population
      of elderly Italians. MATERIAL AND METHODS: Dental, social, and disease conditions
      were evaluated in a large community-based cohort (3054) of elderly subjects (> or
      =65 years) of both sexes in northern Italy. Logistic regression analyses with
      stepwise forward selection were performed to estimate the independent
      contribution of nutritional, socio-economic, and lifestyle variables to dental
      status. Adjusted ORs and 95% CI were estimated for variables significantly
      associated with edentulism. RESULTS: The prevalence of edentulism was about
      44.0%. It was more pronounced in females and it was twice as prevalent in the 90+
      years age group. Among edentulous subjects, 17.5% wore no prostheses.
      Difficulties in chewing and in swallowing were reported by 47.6% and 13.7% of the
      subjects, respectively. Multivariate analysis indicates that edentulism was
      associated with age in both sexes. For women, independently associated risk
      factors were: years since menopause >23 (OR = 1.81; 95% CI: 1.37-2.40), number of
      children >3 (OR = 1.95; 95% CI: 1.36-2.80), and living alone (OR = 1.47; 95% CI:
      1.15-1.88). For men, these were serum albumin <40 g/l (OR = 1.79; 95% CI: 1.22
      2.63), current smoking (OR = 4.01; 95% CI: 2.59-6.20), and former smoking (OR =
      3.42; 95% CI: 2.42-4.82). CONCLUSIONS: The prevalence of edentulism among the
      elderly Italian population studied was at the high end among Western countries,
      and higher in women than in men. In women, tooth loss correlated with aging,
      female events (pregnancies, menopausal status), and living alone. In men, aging
      and smoking are important determinants of edentulism, which is associated with
      the risk condition of hypoalbuminemia. Difficulty in chewing was associated with
      dentition type. In our study, the high prevalence of edentulous subjects without
      prostheses suggests a need for educational and social measures to improve
      patients' attitudes to dental care and to encourage the use of prostheses among
      the elderly.

PMID- 17453426
TI  - Oral health-related knowledge, attitudes, behavior, and family characteristics
      among Finnish schoolchildren with and without active initial caries lesions.
AB  - OBJECTIVE: The aim of this study was to determine whether the presence of active
      initial caries lesions among 11 to 12-year-old schoolchildren is associated with
      parental and child-related factors and whether there are gender differences in
      these associations. MATERIAL AND METHODS: The data were gathered by
      questionnaires from children and their parents, who replied without knowing the
      other's answers. All the children were invited to participate in a screening for
      the presence or absence of active initial caries lesions. Factors associated with
      children's initial caries were studied with logistic regression analyses.
      RESULTS: The parents' self-assessed poor dental health, the parents' and the
      child's poor oral health-related behavior, and the child's response "I don't
      know" to the question concerning his/her parents' possible dental caries were
      associated with the presence of active initial caries lesions. The results of
      logistic regression analyses were different between girls and boys. Among the
      girls, many parent-related factors were associated with the presence of initial
      caries. Among the boys, most factors were related to the child; and of the parent
      related factors, only parents' poor self-assessed dental health was associated
      with initial caries; the effect was modified by the father's occupational level.
      CONCLUSIONS: Parental factors affect boys' and girls' dental health differently.
      Among boys, the effect of the fathers was seen as the father's occupational
      level; among girls, parental knowledge and behavior were important. When school
      interventions to promote health are planned, the important role of the parents
      should be emphasized.

PMID- 17453427
TI  - Dental fear among population aged 30 years and older in Finland.
AB  - OBJECTIVE: The aim of the study was to examine how the percentage of subjects
      reporting dental fear varied in accordance with age, gender, level of educational
      attainment, and marital status in a nationally representative sample of the adult
      population in Finland. MATERIAL AND METHODS: The two-stage stratified cluster
      sample (n=8028) represented the population aged 30 years or older living in
      Finland. Of this nationwide sample, 88% participated. Dental fear was measured
      with the question: "How afraid are you of visiting a dentist?" The reply
      alternatives were: "Not at all", "Somewhat", and "Very much". Age-specific
      multiple logistic regression analyses were used to explore the associations
      between dental fear and age, gender, marital status, and level of educational
      attainment. RESULTS: Overall prevalence of being somewhat or very afraid of
      visiting a dentist among adults in Finland was high (37%), particularly among 30
      to 34-year-olds (47%). Among men and women of different ages, 5% to 19% were very
      afraid and 16% to 59% at least somewhat afraid of visiting a dentist. Female
      gender was the best determinant of dental fear. Those with higher educational
      attainment were about half as likely to be very much afraid of dentistry compared
      to those with secondary educational attainment. Among the youngest age group, non
      singles were more likely to report being very much afraid of dentistry than
      single subjects. CONCLUSIONS: The fairly high prevalence of reported dental fear
      among adults, especially in the youngest age group, presents a challenge to
      dental personnel in Finland.

PMID- 17453428
TI  - Relationship between cognitive impairment and oral health: results of the Health
      2000 Health Examination Survey in Finland.
AB  - OBJECTIVE: The aim was to study oral health in relation to cognitive impairment
      in the general population. MATERIAL AND METHODS: The study population comprised
      2320 persons aged 55 years or older who participated in a nationally
      representative Health 2000 Health Examination Survey in Finland. The data were
      collected by interviews and clinical oral examinations. Cognition was assessed
      using a shortened version of the Mini-Mental State Examination (score 0-16).
      Poisson regression models were used to estimate the relative risk (RR) for
      continuous variables and logistic regression models to estimate the odds ratio
      (OR) for dichotomized variables. RESULTS: The results show that individuals with
      cognitive impairment have more carious teeth (MMSE 11-10: RR: 1.3, CI: 0.9-1.7,
      MMSE 9-0: RR: 1.5 CI: 1.0-2.4) than healthy persons. Furthermore, compared to
      cognitively healthy subjects, those with MMSE 9-0 more often have no teeth and no
      dentures (OR: 5.2, CI: 1.0-26.6) and less often good denture hygiene (OR: 0.4,
      CI: 0.2-0.7). CONCLUSION: Cognitively impaired subjects among older adults in
      Finland have more carious teeth, are more often edentulous without using a
      denture, and have poorer denture hygiene than cognitively healthy persons.

PMID- 17453429
TI  - Validation and improvement of a predictive model for treatment outcome in
      patients with temporomandibular disorders.
AB  - OBJECTIVE: To examine whether it was possible to improve individual prediction of
      treatment outcome in patients with temporomandibular disorders (TMD) through
      continuous quality improvement registrations and implementation of changes in
      clinical routines. MATERIAL AND METHODS: All 5777 patients referred to a
      specialist clinic for stomatognathic physiology; 2187 TMD patients started
      treatment. The patients were divided into Muscle or Mainly TMJ symptom groups.
      Actual treatment outcome was predicted as Good or Dubious based on patient
      history and clinical findings. The degree of improvement of initial symptoms was
      graded using a numeric rating scale 0-100. Improvement in initial complaints of
      50% or more was judged as a clinically important difference (CID); 989 patients
      (76%) completed treatment 1992-1998 (Sample 1) and 769 (86%) treatment 1999-2004
      (Sample 2). RESULTS: For patients with Muscle symptoms in Sample 1, CID was
      reached by 90% of those predicted Good and by 56% of those predicted Dubious. In
      Sample 2, the figures were Good 93% and Dubious 57%. In subgroup Mainly TMJ
      symptoms, CID was reached by 94% of those predicted Good and by 88% if predicted
      Dubious in Sample 1. In Sample 2, the figures were the same for those predicted
      Good, i.e. 94%, and Dubious, 73%. CONCLUSION: Continuous quality improvement
      registrations and implementation of changes in clinical routines improved the
      ability to predict individually the actual treatment outcome between patients
      predicted Good or Dubious, respectively. Rheumatic disease turned out not to be a
      negative predictor for treatment outcome.

PMID- 17453430
TI  - Incidence and prevalence of temporomandibular joint pain and dysfunction. A one
      year prospective study of university students.
AB  - OBJECTIVE: The aims of this study were to investigate the incidence and recovery
      of temporomandibular joint (TMJ) pain and dysfunction during a 1-year period, and
      to examine factors associated with TMJ signs and symptoms. MATERIAL AND METHODS:
      The study population comprised 371 dental students examined at the start of
      education, out of which 308 were re-examined after 1 year. Case histories were
      collected with the aid of a questionnaire. The clinical examination involved TMJ
      mobility, TMJ pain, TMJ sounds, morphological and functional dental occlusion.
      RESULTS: The 1-year incidence of TMJ signs and/or symptoms was 12%, with no
      statistically significant difference between men and women. Reported TMJ sounds
      (10%) and clinically registered TMJ pain (8%) reached the highest incidence
      rates. Approximately a quarter of those who had TMJ signs and/or symptoms at
      baseline had recovered at follow-up. Subjects with a non-symptomatic TMJ were
      significantly more often found among men and among those with bilateral contacts
      in centric relation, a normal transverse inter-maxillary relationship, and a
      stabile mandibular position in centric occlusion. CONCLUSION: The 1-year
      incidence of TMJ pain and/or dysfunction was high among 1st-year university
      students. The persistence of signs and symptoms during the observation period was
      related to gender, while incidence and disappearance of symptoms were not. Dental
      occlusion was not rejected as a possible concurrent factor in relation to TMJ
      pain and/or dysfunction among university students.

PMID- 17453433
TI  - Non-organic hearing loss.
AB  - CONCLUSION: Most non-organic hearing loss (NOHL) patients were young females. The
      discrepancy between the results of pure tone audiometry and objective auditory
      testing suggests NOHL. The diagnostic problem is that objective audiometry is not
      included in routine examinations and we have to suspect NOHL in order to perform
      further examination. The correct diagnosis can be difficult in patients who
      present with unilateral sudden hearing loss or who also have moderate to profound
      organic hearing loss. OBJECTIVE: Symptoms and results of auditory tests for NOHL
      patients were reviewed. PATIENTS AND METHODS: This study comprised 31 patients
      with NOHL. Age, symptoms, and the results of subjective and objective audiometry
      were collected. RESULTS: Twenty-four patients were female and 7 were male. The
      age at attendance ranged from 7 to 39 years old, with an average age of 16.6
      years. Eight patients received steroids before the correct diagnosis was made.
      Six of them presented with unilateral sudden hearing loss, and the other two
      patients had accompanying bilateral organic hearing loss.

PMID- 17453434
TI  - c-Fos expression in the mouse brainstem after unilateral labyrinthectomy.
AB  - CONCLUSION: The results indicated that the vestibular, prepositus hypoglossal,
      and inferior olive nuclei were activated after unilateral labyrinthectomy in mice
      like in other species. It is expected that the application of the present
      procedure to appropriate gene-deficient mice will elucidate the mechanism of the
      process of vestibular compensation. OBJECTIVE: Vestibular compensation is
      attributed to functional and structural reorganization of neural networks in the
      central vestibular system, but its precise mechanism is still not clear. c-Fos
      protein is used as a marker of neuronal activation, because of its very limited
      expression in the normal state and rapid appearance after external stimulation.
      Previous reports, investigating c-Fos expression after unilateral labyrinthectomy
      were made in rats and guinea pigs, but not in the mouse brainstem. MATERIALS AND
      METHODS: For future application to the gene knockout mouse, we examined c-Fos
      expression in the mouse after unilateral labyrinthectomy. RESULTS: Twenty-four
      hours after surgery, significantly increased c-Fos positive cells were observed
      in the bilateral medial vestibular nucleus (MVe), bilateral spinal vestibular
      nucleus (SpVe), contralateral prepositus hypoglossal nucleus (PrH), and
      contralateral inferior olive nucleus (IO).

PMID- 17453435
TI  - Vertigo as the sole presenting symptom of cerebellopontine angle meningioma.
AB  - We report a rare case of cerebellopontine angle (CPA) meningioma whose sole
      symptom was severe vertigo. A 39-year-old woman with right CPA meningioma was
      referred for surgery. She experienced severe vertigo for 2 years without any
      other symptoms. Caloric test indicated right canal paresis of 90%. Her audiogram
      was normal. After surgery, vertigo symptoms disappeared dramatically. The
      mechanisms of restoration from vertigo are discussed.

PMID- 17453436
TI  - A case of cochlear implant with internal mechanical failure.
AB  - Cochlear implantation has been performed since the 1970s and has been proven to
      be an effective treatment for profoundly deaf people. In some cases re
      implantation has also been reported due to trauma causing implant damage,
      mechanical failure, extrusion, and wound infections, or device upgrade. We
      present a case of a 9-year-old boy with a cochlear implant in which mechanical
      failure occurred after a blow to his temporal region. The clinical presentation
      and radiographic imaging findings suggested that the cause of mechanical failure
      was internal failure. We performed cochlear re-implantation to the same ear and
      it worked well. The explanted device analysis by the manufacturer concluded that
      the device had failed due to a cracked hybrid integrated circuit.

PMID- 17453437
TI  - Cochlear implants in post-lingually deafened patients.
AB  - CONCLUSION: Post-lingually deafened patients had good speech intelligibility
      scores with cochlear implantation. The age at the operation, duration of
      deafness, and the number of electrodes outside the cochlea showed only weak
      correlation with the postoperative performance, which warrants cochlear
      implantation in elderly patients and patients with a long history of deafness and
      leaving dummy electrodes outside the cochlea. Patients with cochlear obstruction
      showed comparable performance to patients with an open cochlea. OBJECTIVE: To
      evaluate the background and performance of post-lingually deafened cochlear
      implantation recipients. PATIENTS AND METHODS: Preoperative and intraoperative
      factors were collected for 109 cochlear implant subjects. Speech intelligibility
      scores were obtained and the effects of preoperative and intraoperative factors
      on postoperative performance were evaluated. RESULTS: The average speech
      intelligibility score was 85.1% for vowels, 41.1% for consonant-vowel (CV)
      syllables, and 80.4% for phrases. The correlation coefficient between the age at
      the operation, the duration of deafness, and the number of electrodes outside the
      cochlea and the postoperative performance was between 0.03 and -0.27. Patients
      with cochlear obstruction and patients with open cochlea did not show significant
      differences in speech intelligibility tests. The onset of deafness (progressive
      vs sudden) did not have an effect on the speech intelligibility test.

PMID- 17453438
TI  - Clinical characteristics of delayed endolymphatic hydrops: long-term results of
      hearing and efficacy of hyperbaric oxygenation therapy.
AB  - CONCLUSION: Diuretics significantly improved hearing in patients with
      contralateral-type DEH, whereas they did not inpatients with ipsilateral-type
      DEH. OBJECTIVE: We report a review of 26 cases of DEH treated in recent 6 years.
      PATIENTS AND METHODS: The study group comprised 22 contralateral and 4
      ipsilateral types of DEH. The efficacy of diuretics on the improvement in hearing
      was examined quantitatively. The efficacy of hyperbaric oxygenation therapy (HBO)
      on hearing was examined in six patients. RESULTS: The general properties of these
      cases were similar to those reported previously, except for the high proportion
      of patients with contralateral-type DEH. Diuretics significantly improved the
      hearing of patients with contralateral-type DEH. In contrast, no significant
      improvement by diuretics was noted in ipsilateral-type DEH.

PMID- 17453439
TI  - Severe acoustic trauma in adult rats induced by short duration high intensity
      sound.
AB  - CONCLUSION: Short duration high intensity sound (SDHIS) induced severe functional
      damage in adult rats. OBJECTIVE: Previous reports showed that SDHIS induced
      severe histological changes in the cochleae of guinea pigs. This study examined
      the hearing functions of rats exposed to SDHIS. MATERIALS AND METHODS: Animals
      were exposed for 1 min to a 137 dB sound pressure level (SPL) broadband noise.
      Auditory functions of the experimental animals were assessed using an auditory
      brainstem response (ABR) measurement system at frequencies of 8, 16, and 32 kHz
      before and 14 days after exposure to SDHIS. RESULTS: After SDHIS, none of the
      experimental animals showed any response when stimulated by maximum SPLs at all
      frequencies of our ABR system.

PMID- 17453440
TI  - Drug delivery systems for the treatment of sensorineural hearing loss.
AB  - Sensorineural hearing loss is one of the most common disabilities in our society.
      Experimentally, many candidates for therapeutic molecules have been discovered.
      However, the lack of safe and effective methods for drug delivery to the cochlea
      has been a considerable obstacle to clinical application. Local application of
      therapeutic molecules into the cochlea has been used in clinic and in animal
      experiments. Advances in pharmacological technology provide various drug delivery
      systems via biomaterials, which can be utilized for local drug delivery to the
      cochlea. Recent studies in the field of otology have demonstrated the potential
      of synthetic and natural biomaterials for local drug delivery to the cochlea.
      Although problems still remain to be resolved for clinical application,
      introduction into clinical practice of these controlled-release systems may be
      reasonable because of their certain advantages over previous methods.

PMID- 17453441
TI  - Effects of bone morphogenetic protein 4 on differentiation of embryonic stem
      cells into myosin VIIa-positive cells.
AB  - CONCLUSION: Our results indicate that myosin VIIa-positive cells are generated
      from embryonic stem cells (ESCs) co-cultured with PA6 cells; however, bone
      morphogenetic protein 4 (BMP4) may not be a key molecule for induction of myosin
      VIIa-positive cells from the ESCs. BACKGROUND: ESCs have been considered as a
      basis for cell therapy in a range of organs, because of their potential for self
      renewal and pluripotency. Co-culture with PA6 stromal cells can induce
      differentiation of ESCs into various types of ectodermal cells including sensory
      progenitors. BMP4 plays an essential role in the development of sensory hair
      cells in the inner ear. MATERIALS AND METHODS: We examined effects of BMP4 on
      differentiation of ESCs into the hair cell immunophenotype. BMP4 was supplemented
      at different time points to ESCs co-cultured on PA6 stromal cells. The ESCs were
      then collected and examined for the expression of myosin VIIa, a hair cell
      marker, and betaIII-tubulin, a neural marker. The expression of myosin VIIa and
      betaIII-tubulin was identified. RESULTS: Quantitative assessments revealed that
      exogenous BMP4 has significant effects on the expression of betaIII-tubulin, but
      not of myosin VIIa.

PMID- 17453442
TI  - Bilateral congenital ossicular chain disruption mimicking otosclerosis.
AB  - A rare case of bilateral congenital ossicular chain disruption whose history and
      findings mimicked those of otosclerosis is reported. A 54-year-old male consulted
      us for slowly progressing hearing loss. Audiogram showed bilateral intermediate
      mixed hearing loss. The stapedial reflex was negative and the tympanogram was
      normal A-type. Based on the diagnosis of otosclerosis, stapes surgery was planned
      for the left side. Surgical findings revealed normal mobility of the stapes and a
      small disruption at the incudostapedial joint with connection of intact mucosa.
      The disruption was repaired with auto-bone columella. The patient's hearing
      improved after surgery. The surgery for the other side was performed
      successively, and similar ossicular disruption was observed. The mechanisms of
      findings that misled the preoperative diagnosis are discussed.

PMID- 17453443
TI  - Stabilization technique for columella using trimmed autologous temporal fascia in
      type III and IV tympanoplasty--Muffler method.
AB  - CONCLUSION: High success rates of recovery of hearing level in type III and IV
      tympanoplasty could be achieved by this stabilization technique for columella
      using trimmed autologous temporal fascia. OBJECTIVE: The aim of this study was to
      evaluate a new stabilization technique for columella using trimmed autologous
      temporal fascia in type III and IV tympanoplasty. PATIENTS AND METHODS: A total
      of 55 patients (21 male, 34 female, aged 4-85 years) with chronic otitis media
      (n=16) and cholesteatoma (n=39) underwent tympanoplasty using this new
      stabilization technique for columella. Thirty-one patients underwent type III
      tympanoplasty and 24 patients underwent type IV tympanoplasty. Forty-two patients
      underwent a staged operation and 13 patients underwent a single operation. The
      observation period was 3.5 years from 6 months after the last operation. RESULTS:
      The overall success rates in type III and IV tympanoplasty were 87.1% (27/31) and
      83.3% (20/24), respectively. Two of eight patients for whom the procedure was
      unsuccessful underwent reoperation and they acquired good hearing.

PMID- 17453444
TI  - Cholesterol granuloma of the posterior ethmoid sinus mimicking meningocele.
AB  - Cholesterol granuloma is usually associated with chronic middle ear disease, less
      common in the orbit, and rare in the paranasal sinus. Cholesterol granuloma is
      thought to be initiated by hemorrhage, impaired drainage, and interruption of
      aeration. Here we report a case of cholesterol granuloma arising in the posterior
      ethmoid sinus mimicking meningocele. Magnetic resonance imaging is useful for
      differential diagnosis, and endoscopic surgery is effective for the management of
      cholesterol granuloma arising in the ethomoid sinus.

PMID- 17453445
TI  - Endoscopic modified Lothrop procedure for postoperative frontal mucocele.
AB  - CONCLUSION: The endoscopic modified Lothrop procedure was found to be useful for
      management of postoperative frontal mucocele. OBJECTIVE: The aim of this study
      was to evaluate the efficacy of the endoscopic modified Lothrop procedure, in
      which bone resection in the lateral aspect of the frontal recess and frontonasal
      duct was avoided, for management of postoperative frontal mucocele. PATIENTS AND
      METHODS: The study prospectively assessed six patients who underwent an
      endoscopic modified Lothrop procedure. Patients had undergone a mean of two
      previous sinus surgical procedures. In our procedure, the mucosa and bone of the
      lateral aspect of the frontal recess and frontonasal duct were preserved, while a
      median drainage in the frontal sinus floor was created as large as possible.
      RESULTS: All patients had a patent median drainage pathway and were free from
      preoperative symptoms with an average follow-up of 24.5 months. Although scar
      formation in the anterior aspects of the frontal recess was observed, no patients
      required revision surgery.

PMID- 17453446
TI  - A rare case of hyperfunctioning papillary carcinoma of the thyroid gland.
AB  - We report a rare case of hyperfunctioning papillary carcinoma of the thyroid. A
      32-year-old man was referred to our hospital for the treatment of a painless mass
      in the left neck, which had been detected on routine physical check-up. Cervical
      ultrasonography and computed tomography showed a solid tumor with calcification
      in the left lobe of the thyroid gland. Serum examinations demonstrated
      hyperthyroidism with a high level of thyroglobulin. Fine needle aspiration biopsy
      revealed a cytological diagnosis of class II. Tc-99m scintigraphy showed a hot
      nodule in the left lobe, which implied that the tumor was a hyperfunctioning
      thyroid tumor. Left lobectomy of the thyroid gland was performed to treat the
      hyperfunctioning tumor. Postoperative pathological examinations revealed a
      follicular variant papillary carcinoma. Postoperative thyroid function became
      within the normal range. Although hyperfunctioning thyroid carcinomas are rare,
      it is important to correctly diagnose them and to perform appropriate surgical
      interventions.

PMID- 17453447
TI  - Therapeutic outcomes of oral cancers at Kyoto University Hospital.
AB  - CONCLUSION: The results suggest that early diagnosis and treatment are the most
      important factors to improve the prognosis in oral cancer patients. OBJECTIVE: In
      this retrospective study we analyzed the therapeutic outcome of oral cancers at
      out institute. PATIENTS AND METHODS: Thirty-one patients with oral cancers were
      treated between January 2000 and December 2004 at the Department of
      Otolaryngology-Head and Neck Surgery, Kyoto University Hospital. Transoral
      resection of tumor with or without neck dissection was performed for early oral
      cancers (stage I and II), while more extensive resection and radical neck
      dissection followed by postoperative radiotherapy was performed for advanced
      cases (stage IIII and IV). In the treatment of early tongue cancer, either
      partial glossectomy or brachytherapy was selected. The 3-year disease-specific
      survival rates of all patients, early-staged, and advanced-staged patients were
      82.2%, 92.9%, and 63.5%, respectively. The prognosis was significantly related to
      the clinical stage of the tumor.

PMID- 17453448
TI  - Therapeutic outcomes of laryngeal cancer at Kyoto University Hospital for 10
      years.
AB  - CONCLUSION: It is important to prevent regional lymph node recurrence and distant
      metastasis to achieve better survival of laryngeal cancer. OBJECTIVE: Therapeutic
      outcomes of 130 cases with laryngeal cancer treated at Kyoto University Hospital
      between 1995 and 2004 were reviewed. PATIENTS AND METHODS: In all, 121 males and
      9 females were involved. Their ages ranged from 40 years to 92 years (average 66
      years). All tumors were squamous cell carcinoma - arising at the glottis in 111
      cases, the supraglottis in 18, and the subglottis in 1 case. Most glottic cancers
      (77.5%) were classified as stage I or II, while most supraglottic cancers (77.8%)
      were at stage III or IV. Stage I/II cancers were basically treated by
      conventional radiotherapy (60-66 Gy) and twice-daily hyperfractionated
      radiotherapy (70-74 Gy), respectively, attempting to preserve the larynx. Total
      laryngectomy with neck dissection was performed in the treatment of stage III/IV
      cases. RESULTS: Five-year disease-specific survival rates were 100%, 96%, 100%,
      and 68% for stage I, II, III, and IV, respectively. Five-year laryngeal
      preservation rates were 98%, 100%, 86%, 0%, and 0% for T1a, T1b, T2, T3, and T4
      of glottic cancer, respectively. Local recurrence occurred in five cases of stage
      I/II glottic cancer, which was successfully salvaged. Regional lymph node
      recurrence occurred in five cases including four patients with glottic cancer and
      one with supraglottic cancer. Two of them died of disease despite undergoing
      salvage therapy. Distant metastasis occurred in the lung in four cases including
      one glottic and three supraglottic cancer patients after initial treatment.

PMID- 17453449
TI  - Experimental regeneration of canine larynx: a trial with tissue engineering
      techniques.
AB  - CONCLUSION: Since this tissue engineering technique is cost-effective and is less
      invasive to patients, it may replace conventional approaches in laryngeal
      reconstructive surgeries. OBJECTIVE: Laryngeal cancer is one of the most
      prevalent cancers in the head and neck region, and frequently requires surgical
      resection. Although there are many ways to reconstruct the larynx after
      resection, donor tissue is usually required. Recently, tissue engineering
      techniques have become widely accepted in clinical medicine and have already been
      applied to some organs. This animal experiment was designed to elucidate the
      efficacy of laryngeal regeneration using tissue engineering technique. MATERIALS
      AND METHODS: A bioartificial scaffold was designed from a replica of a canine
      larynx. A dental cast was used to replicate the intricate inside shape of the
      larynx. After copying its shape on a polypropylene mesh sheet, this sheet was
      coated with spongy collagen from porcine skin. A hemilaryngectomy was performed
      on beagle dogs under general anesthesia. Then the scaffold, preclotted with a
      mixture of peripheral blood and bone marrow-derived stromal cells, was implanted
      and fixed. The postoperative status was examined fiberscopically. RESULTS: On the
      eighth day after the operation, the surface of the implant was covered with soft
      tissue. Finally, the implant was completely covered with regenerated mucosa.

PMID- 17453450
TI  - Granular cell tumor of hypopharynx: report of a rare case.
AB  - Granular cell tumor is a rare tumor, probably of Schwann cell origin. The head
      and neck are most frequently affected, but hypopharyngeal lesion is extremely
      rare. We report the seventh case of hypopharyngeal granular cell tumor.
      Immunohistochemical staining for S100 protein is helpful for the correct
      diagnosis. There is some possibility of malignancy despite absence of
      histological evidence, thus the treatment is exclusively surgical resection. The
      microlaryngoscopic approach is feasible for hypopharyngeal lesions in most cases.
      Recurrence can occur even after appropriate resection.

PMID- 17453451
TI  - Gene expression and plasticity in the rat auditory cortex after bilateral
      cochlear ablation.
AB  - CONCLUSION: The plastic changes in the auditory cortex after bilateral cochlear
      ablation are related to the immediate early genes as well as the neural
      plasticity-related genes. In addition, cross-modal plasticity may play an
      important role in the early changes in the auditory cortex after bilateral
      cochlear ablation. OBJECTIVES: The purpose of this study was to identify
      candidate genes involved in the normal development of primary auditory cortex
      during the critical period as well as those genes specifically modulated under
      conditions of sensory deafferentation by bilateral cochlear ablation. MATERIALS
      AND METHODS: We produced a bilaterally deaf rat model and used DNA microarray
      technology to analyze differential gene expression in the primary auditory cortex
      of bilateral cochlear ablated and sham-operated age-matched control rats. Gene
      expression in the auditory cortex was compared at 2, 4, and 12 weeks after
      surgery. For selected genes, the changes in gene expression were confirmed by
      real-time polymerase chain reaction (PCR). RESULTS: In the cochlear ablation
      groups, the expression of immediate early genes (Egr1, 2, 3, 4, c-fos, etc.) and
      neural plasticity-related genes (Arc, Syngr1, Bdnf, etc.) was decreased at 2
      weeks and increased at 4 weeks. The expression of neurotransmission-related genes
      (Gabra5, Chrnb3, Chrne, etc.) was decreased at 12 weeks.

PMID- 17453452
TI  - Dendritic and spinal pathology in the acoustic cortex in Alzheimer's disease:
      morphological and morphometric estimation by Golgi technique and electron
      microscopy.
AB  - CONCLUSIONS: The morphological and morphometric estimation of the dendrites and
      the dendritic spines in the acoustic cortex in Alzheimer's disease revealed
      substantial alterations of the dendritic arborization and marked loss of the
      dendritic spines. This may be related to communication impairment even in early
      cases of Alzheimer's disease. OBJECTIVES: Alzheimer's disease is characterized by
      progressive loss of memory, impairment of judgment, and decline in communication
      and speech eloquence. In the present study we attempted to describe the
      morphological and morphometric alterations of the dendrites and the dendritic
      spines in the acoustic cortex in early cases of Alzheimer's disease, in order to
      approach the communication impairment of patients suffering from Alzheimer's
      disease, from the neuropathological point of view. MATERIALS AND METHODS: We
      studied the acoustic cortex in 22 cases of Alzheimer's disease by Golgi technique
      and electron microscopy. RESULTS: The morphological and morphometric estimation
      of the acoustic cortex revealed loss of Cajal-Retzius cells in layer I, as well
      as an impressive abbreviation of the dendritic fields associated with loss of
      dendritic spines in all layers of the cortex. Numerous distorted, dystrophic and
      degenerated dendritic spines were also seen, which were intermixed with a
      considerable number of giant spines. The dendritic and spinal alterations were
      closely associated with mitochondrial alterations.

PMID- 17453453
TI  - Unusual cases of delayed endolymphatic hydrops.
AB  - The objective of this report is to emphasize the clinical features of delayed
      endolymphatic hydrops in comparison with Meniere's disease. Four cases were
      selected from a series of 16 examined between the years 1993 and 2005, due to
      their unusual characteristics. A short clinical history and significant tests are
      presented for each of the four cases. The cases of delayed endolymphatic hydrops
      discussed in this article suggest that hydrops is the most important underlying
      pathology that causes the hearing loss and the vestibular symptoms both in the
      better ear and in the ear with severe hearing loss. They also suggest that this
      condition probably occurs in patients with congenitally sensitive ears that make
      them prone to the development of the late hydrops.

PMID- 17453454
TI  - Intraoperative ossicular loading with the Otologics fully implantable hearing
      device.
AB  - CONCLUSIONS: Use of the recently introduced intraoperative loading
      instrumentation during surgery improves the coupling efficiency and consistency
      of a fully implantable hearing device to the ossicles and ultimately leads to
      better patient performance with the device. BACKGROUND: Patient performance with
      an implantable hearing device is dependent on effective coupling of the implant
      to the middle ear ossicles. New intraoperative instrumentation aids the surgeon
      in coupling the implantable hearing device and consistently optimizes patient
      performance. MATERIALS AND METHODS: The middle ear transfer function for the
      Otologics MET Ossicular Stimulator (METF(MET)) is a measure of transducer
      coupling efficiency, defined as acoustic threshold (in dB HL) minus implant
      threshold (in dB MET). This transfer function was measured in the Otologics US
      Phase I Semi-Implantable Clinical Trial without intraoperative loading
      instrumentation and in the Otologics US Phase I Fully Implantable Clinical Trial
      with intraoperative loading instrumentation. The same operative techniques and
      transducer design were used in both studies. The theory of operation and surgical
      technique for using this instrumentation are described. RESULTS: In the semi
      implantable clinical trials, METF(MET) was -10 to -15 dB for frequencies above 1
      kHz, and dropped to -15 to -20 dB for lower frequencies. Fully implantable
      clinical trial results were 10-20 dB better than the semi-implantable trial
      results, with less variability at all frequencies. These findings indicate more
      consistent and better coupling efficiency of the transducer to the ossicles.

PMID- 17453455
TI  - Recognition of lexical tone production of children with an artificial neural
      network.
AB  - CONCLUSION: This study demonstrated that the artificial neural network can
      successfully classify Mandarin Chinese tone patterns produced by multiple
      children. The neural network can be used as an objective way of evaluating tone
      production of children. OBJECTIVES: Traditionally, tone production is evaluated
      subjectively using human listeners. The aim of the present study was to
      investigate the efficacy of using an artificial neural network in evaluating tone
      production of Mandarin-speaking children. SUBJECTS AND METHODS: Speech materials
      were recorded from 61 normal-hearing children. The fundamental frequency (F0) of
      each monosyllabic word was extracted and then used as inputs to a feed-forward
      backpropagation artificial neural network. The number of inputs was set at 12,
      whereas the number of hidden neurons was set at 16 in the neural network. The
      output layer consisted of four neurons representing the four Mandarin tone
      patterns. The tone recognition performance of the neural network was further
      compared with that of native Mandarin-speaking adult listeners. RESULTS: The
      neural network successfully classified the tone patterns of the 61 child speakers
      with an accuracy of about 85% correct. This high accuracy exceeded the tone
      recognition performance by the adult listeners. Individual child speakers showed
      varied tone production accuracy as recognized by the adult listeners or by the
      neural network.

PMID- 17453456
TI  - Differences between electrode-assigned frequencies and cochlear implant recipient
      pitch perception.
AB  - CONCLUSION: This study demonstrated an evident mismatch between frequencies
      assigned to electrodes and frequencies evoked by stimulation of those same
      electrodes in implanted patients. We propose that the mapping procedures should
      include, whenever possible, a comparison with homolateral residual hearing in
      order to obtain an appropriate frequency range assignation for each electrode.
      OBJECTIVES: The study aimed to investigate the correspondence between the
      frequencies assigned to each electrode and those actually perceived by the
      cochlear implant patient. PATIENTS AND METHODS: We studied five post-lingually
      deaf adults with detectable residual hearing in the implanted and in the
      contralateral ear, who had each received a Cochlear implant. An ACE standard
      setting was used for mapping. The patients were asked to match the electric pitch
      with the acoustic one following presentation of pure tones to both the implanted
      and the contralateral ear. RESULTS: In almost all patients the two most apical
      electrodes evoked higher frequencies than those assigned by the mapping software
      (E22 = 188-313, E21 = 313-438 Hz). Therefore, electric stimulation seems not to
      determine pitch sensations for frequencies <500 Hz. For most electrodes there is
      no correspondence between the acoustic pitch and the assigned frequency ranges.
      Moreover, these results were almost always different when stimulating the
      implanted and the contralateral ear.

PMID- 17453457
TI  - The effect of perimodiolar placement on speech perception and frequency
      discrimination by cochlear implant users.
AB  - CONCLUSION: Neither speech understanding nor frequency discrimination ability was
      better in Nucleus Contour users than in Nucleus 24 straight electrode users.
      Furthermore, perimodiolar electrode placement does not result in better frequency
      discrimination. OBJECTIVES: We addressed three questions related to perimodiolar
      electrode placement. First, do patients implanted with the Contour electrode
      understand speech better than with an otherwise identical device that has a
      straight electrode? Second, do these groups have different frequency
      discrimination abilities? Third, is the distance of the electrode from the
      modiolus related to frequency discrimination ability? SUBJECTS AND METHODS:
      Contour and straight electrode users were matched on four important variables. We
      then tested these listeners on CNC word and HINT sentence identification tasks,
      and on a formant frequency discrimination task. We also examined X-rays and
      measured the distance of the electrodes from the modiolus to determine whether
      there is a relationship between this factor and frequency discrimination ability.
      RESULTS: Both speech understanding and frequency discrimination abilities were
      similar for listeners implanted with the Contour vs a straight electrode.
      Furthermore, there was no linear relationship between electrode-modiolus distance
      and frequency discrimination ability. However, we did note a second-order
      relationship between these variables, suggesting that frequency discrimination is
      worse when the electrodes are either too close or too far away from the modiolus.

PMID- 17453458
TI  - Correlation of hearing screening with developmental outcomes in infants over a 2
      year period.
AB  - CONCLUSION: Evoked otoacoustic emission (OAE) and auditory brainstem response
      (ABR) results for hearing screening among infants have good concordance. However,
      good correlation with the Griffiths Developmental Scales remains to be desired.
      OBJECTIVE: To correlate hearing screening outcomes of a cohort of infants with
      developmental outcomes at 6 and 12 months. SUBJECTS AND METHODS: A cohort of
      pregnant women was identified in several communities in a rural area (Bulacan
      province) from April 2002 to February 2003 as part of a population-based study
      determining maternal exposure to pollutants and infant outcomes, with a total
      follow-up of 2 years. Pregnant mothers were identified and followed up until
      delivery at a secondary, provincial hospital. Hearing screening was performed
      with OAEs and ABR. Mental development of infants was assessed at 6 and 12 months
      using Griffiths Mental Developmental Scales - locomotor, personal-social, hearing
      and speech, hand and eye coordination, performance tests. RESULTS: Among the 1086
      babies recruited, there were 724 with hearing assessment. Of these 724 babies,
      565 had both OAE testing and ABR. Overall in 1130 ears, OAE and ABR testing
      showed an observed agreement of 99%, agreement due to chance of 96%, and kappa
      agreement of 79% (p=0.00) in diagnosing bilateral hearing losses. OAEs had a
      sensitivity of 86.4% (95% CI 64-96.4%) and a specificity of 99.4% (95% CI 98.6
      99.7%). At the end of the study, there were 708/724 (97.8%) infants with normal
      hearing, 7/724 (1.0%) with unilateral hearing loss, 8/724 (1.1%) with bilateral
      mild hearing loss, and 1/724 (0.1%) with bilateral profound hearing loss, who
      demonstrated consistent mental delay throughout. Follow-up rates for
      developmental examinations at 6 and 12 months were 98% and 81.25%, respectively.
      In these groups, there were 8 (1%) infants at 6 months and 18 (2.4%) at 12 months
      with developmental delay (Griffiths Mental Developmental Scales).

PMID- 17453459
TI  - Initial experiments to develop a MEMS transducer for a new implantable
      audioprosthesis to substitute the tympanic-ossicular system.
AB  - CONCLUSION: We tested one prototype of a new audioprosthesis including the
      audioprocessor, the implemented algorithms and fitting platform in a small group
      of selected patients with mixed hypoacusis due to earlier bilateral radical
      mastoidectomy. It was effective to compensate the conductive and the neurosensory
      components of those patients. Results regarding the energy, frequency and other
      requirements of the output transduction make it possible to develop a suitable
      actuator with the available Micro-Electromechanic-Machine-System (MEMS)
      technology to substitute the conventional transducer of the prototype.
      OBJECTIVES: The objectives were: a) to evaluate the effectiveness of the whole
      fitting system, and b) to obtain information about the required energy to design
      the MEMS actuator. MATERIALS AND METHODS: The experiments were conducted with the
      A prototype of the prosthesis equipped with an output transducer coupled to the
      oval window. Two algorithms and three cases were tested. RESULTS: The
      audioprocessor with the implemented FIR filter-67 coefficients paradigm
      algorithms, and the fitting system were shown to be adequate for clinical use.
      Effectiveness parameters were: pure tone average gains 20-33.3 dB; gap closure
      25.5-31.8 dB; speech reception thresholds improvement 15-20 dB. Required gain: 5
      40 dB. Subjectively, patients considered the results very satisfactory.

PMID- 17453460
TI  - Expression of Toll-like receptors in cultured nasal epithelial cells.
AB  - CONCLUSIONS: Nasal epithelial cells are constitutively equipped with all Toll
      like receptors (TLRs) which are essential for innate immunity. Both mRNA and
      protein levels of TLR3 expression increased in more differentiated nasal
      epithelial cells. Considering that the ligand for TLR3 is viral dsRNA, this
      result is in good accordance with previous reports demonstrating that more
      differentiated airway epithelial cells have increased resistance to rhinovirus
      infection. OBJECTIVE: Nasal epithelial cells use innate immune responses to
      combat inspired potential pathogens. TLRs are receptors that recognize pathogen
      associated molecular patterns of microbes. Therefore, we investigated the
      expression of TLRs in cultured nasal epithelial cells obtained from nasal polyps.
      MATERIALS AND METHODS: Submerged single layer (SSL) and air-liquid interface
      (ALI) nasal epithelial cell cultures with or without 10(-7) M retinoid acid (+/-
      RA) were created. RESULTS: ALI + RA culture developed ciliary differentiation as
      observed by light and scanning electron microscopic examination in 3 weeks. It
      had higher interleukin (IL)-8 basal secretion (21.9 vs 0.82-1.45 ng/ml) and
      transepithelial potential (-20.4 mV). TLR1-10 mRNA expression in cultured nasal
      epithelial cells was determined by RT-PCR. Only TLR3 mRNA significantly increased
      at day 20 vs day 1 (n=5, p=0.02) in ALI + RA cell culture. Higher TLR3 protein
      was also expressed at day 20 in ALI + RA cell culture but not in SSL culture by
      western blotting.

PMID- 17453461
TI  - Impact of a self-developed planning and self-constructed navigation system on
      skull base surgery: 10 years experience.
AB  - CONCLUSION: Our self-developed planning and navigation system has proven its
      capacity for accurate surgery on the anterior and lateral skull base. With the
      incorporation of augmented reality, image-guided surgery will evolve into
      'information-guided surgery'. OBJECTIVE: Microscopic or endoscopic skull base
      surgery is technically demanding and its outcome has a great impact on a
      patient's quality of life. The goal of the project was aimed at developing and
      evaluating enabling navigation surgery tools for simulation, planning, training,
      education, and performance. This clinically applied technological research was
      complemented by a series of patients (n=406) who were treated by anterior and
      lateral skull base procedures between 1997 and 2006. MATERIALS AND METHODS:
      Optical tracking technology was used for positional sensing of instruments. A
      newly designed dynamic reference base with specific registration techniques using
      fine needle pointer or ultrasound enables the surgeon to work with a target error
      of < 1 mm. An automatic registration assessment method, which provides the user
      with a color-coded fused representation of CT and MR images, indicates to the
      surgeon the location and extent of registration (in)accuracy. Integration of a
      small tracker camera mounted directly on the microscope permits an advantageous
      ergonomic way of working in the operating room. Additionally, guidance
      information (augmented reality) from multimodal datasets (CT, MRI, angiography)
      can be overlaid directly onto the surgical microscope view. The virtual simulator
      as a training tool in endonasal and otological skull base surgery provides an
      understanding of the anatomy as well as preoperative practice using real patient
      data. RESULTS: Using our navigation system, no major complications occurred in
      spite of the fact that the series included difficult skull base procedures. An
      improved quality in the surgical outcome was identified compared with our control
      group without navigation and compared with the literature. The surgical time
      consumption was reduced and more minimally invasive approaches were possible.
      According to the participants' questionnaires, the educational effect of the
      virtual simulator in our residency program received a high ranking.

PMID- 17453462
TI  - Medical education by bedside learning - helping medical students to interact with
      patients who have head and neck cancer.
AB  - CONCLUSION: Our bedside interviews with patients with head neck cancer are unique
      and valuable educational experiences for undergraduate medical students.
      OBJECTIVE: How can we help medical students to understand patients' thoughts and
      feelings? We believe that students can learn and practice empathy at the
      patient's bedside. SUBJECTS AND METHODS: Sixty medical students in their final
      year at the University of Tokyo and 10 patients with head and neck cancer were
      supervised by a professor and senior head and neck surgeons. Questionnaires were
      delivered to each student before and after bedside teaching, to investigate their
      impressions on thoughts and feelings of patients with head and neck cancer.
      Questions to patients were composed of: 1) backgrounds: birthplace, education,
      occupation and hobby; 2) cancer: the time of the first visit to clinic and the
      time of referral to the University of Tokyo Hospital; 3) preoperative feelings;
      4) impression of surgical treatment and postoperative care; and 5) messages to
      medical students from the patient. Medical students also asked additional
      questions. RESULTS: Before the bedside teaching our medical students believed
      that it must be important to listen to patients (100%); and that it must be
      possible to encourage patients (50%). After the bedside teaching they noticed
      that a medical interview could have a positive influence on the patient (93%),
      probably because of general conversation (45%), the patient's personality (50%),
      listening to information about the patient's birthplace, education, occupation
      and hobby (48%), and the instructor's life experiences (25%). Most patients asked
      medical students to be good doctors who can understand their thoughts and
      feelings.

PMID- 17453463
TI  - The history of the glomus tumors - nonchromaffim chemodectoma: a glimpse of
      biomedical Camelot.
AB  - CONCLUSIONS: Guild's initial 231 word report was the source of a stream of
      positive consequences; the glomus story is a paradigm of the utility of basic
      science. BACKGROUND: The glomus tumor has had a number of different names,
      including glomus jugulare, glomus tympanicum, nonchromaffin paraganglioma, and
      carotid body tumor. Although they have occurred throughout the ages, glomus
      tumors were neither recognized nor understood until Harry Rosenwasser read Stacy
      Guild's report of 1941. MATERIALS AND METHODS: The pertinent literature from the
      18th century to the present was reviewed. RESULTS: Stacy Guild's pursuit of basic
      scientific knowledge laid the foundation for a chain of clinical and scientific
      advances that continue to the present and will continue to have positive effects
      into the future. Guild's brief basic science note of 1941 was used through the
      scholarship of Rosenwasser to define a clinical entity that had not been
      recognized. This new nosology, rapidly adopted worldwide, provided a biological
      basis for the rational grouping of patients and analysis of their ills.
      Subsequent to this, it was noted that many of these tumors occurred in families,
      apparently transmitted as an autosomal dominate but occurring primarily in the
      males. Further study based on these observations led to the identification of a
      genetic mechanism of inheritance: genomic imprinting. A further advance of the
      synergetic relationship between the environment - oxygen tension/altitude - and
      the mutation explains Guild's 1953 observations that all patients, without any
      sexual predominance, have glomus bodies but not all have tumors.

PMID- 17453464
TI  - The importance of improved nasal breathing: a review of the Nozovent nostril
      dilator.
AB  - The Nozovent nostril dilator improves nasal breathing to the same degree as
      topical decongestants and reduces mouth dryness at night in 51% of nocturnal
      mouth breathers. It does not help every snorer but reduces the snoring heard by
      the sleeping partner in about 50%, improves the respiratory disturbance index
      significantly in 19% and gives less morning and daytime tiredness in 40% of
      snorers. The medium CPAP pressure can be significantly reduced with the dilator.

PMID- 17453465
TI  - Survival signaling and terminal differentiation in cholesteatoma epithelium.
AB  - CONCLUSION: There is a strong indication that epithelial keratinocytes in
      cholesteatoma are protected against apoptosis. The late terminal differentiation
      program in cholesteatoma epithelium is disturbed. OBJECTIVES: Previously, minimal
      apoptosis has been demonstrated in cholesteatoma epithelium. The phosphoinositide
      3-kinase/Akt/protein kinase B (PI3K/Akt/PKB) and the mitogen activated protein
      kinases (MAPK) signaling transduction pathways have been reported to protect
      epithelial cells against apoptosis. Both pathways have also been proven to
      regulate late terminal differentiation of keratinocytes. In cholesteatoma
      epithelium, MAPK activation has been shown to be associated with terminal
      differentiation. The purpose of this study was to investigate whether in human
      cholesteatoma epithelium protection against programmed cell death by means of
      PI3K/Akt survival signaling is present and associated with MAPK activation and
      terminal differentiation. MATERIALS AND METHODS: Fifteen human cholesteatoma and
      patient-matched retro-auricular skin samples were immunohistochemically stained
      for pAkt/PKB, phosphorylated extracellular regulated kinase1/2 (pERK1/2),
      phosphorylated JNK/SAPK, phosphorylated p38, involucrin and filaggrin. Positive
      cells were counted by computer-assisted digital image analysis. RESULTS: Protein
      expressions of pAkt/PKB, pERK1/2, pp38, and involucrin in cholesteatoma
      epithelium were significantly increased when compared with retro-auricular skin
      (p<0.01). Filaggrin expression was significantly decreased (p=0.03). The positive
      correlation was confirmed between both pERK1/2 and pp38, and involucrin (p < or =
      0.05).

PMID- 17453466
TI  - Effects of selective cochlear toxicity and vestibular deafferentation on
      vestibular evoked myogenic potentials in guinea pigs.
AB  - CONCLUSION: The findings suggest that sound-evoked myogenic potentials on the
      guinea pig sternocleidomastoid muscle (SM) originate from the vestibular end
      organ and not from the cochlea of the inner ear. OBJECTIVE: Studies in animals of
      the sound evoked vestibular myogenic potentials on the SM should aid in
      elucidating the pathway of the vestibular-evoked myogenic potential (VEMP).
      However, details of the pathway of the VEMP remain to be elucidated. This study
      aimed to clarify aspects of this pathway. MATERIALS AND METHODS: In the present
      study, short latency biphasic myogenic potentials on the SM in guinea pigs were
      induced by an intense brief sound. RESULTS: The thresholds of the potentials were
      67 dB SPL above those of the auditory brainstem response (ABR). The potentials
      were eliminated by a vestibular deafferentation, but were observed after
      selective cochlea toxicity using an amikacin injection.

PMID- 17453467
TI  - Evaluation of the combined medical and surgical treatment in nasal polyposis. I:
      functional results.
AB  - CONCLUSION: This prospective study is the first in the literature to present long
      term results of a combined medical and surgical treatment in patients with nasal
      polyposis (NP) including strict inclusion criteria, analysis of the results in
      terms of clinical amelioration, polyp size reduction, and steroid consumption.
      The results of the present study show that combined surgery and corticosteroid
      therapy is effective in the treatment of NP. OBJECTIVE: Most publications on
      outcome after functional endoscopic sinus surgery (FESS) include patients with
      various pathologies. The aim of this study was to provide reference information
      for FESS in patients with NP with strict inclusion and exclusion criteria.
      MATERIALS AND METHODS: This was a prospective study involving 194 consecutive
      patients. Clinical symptoms, polyp size, and steroid consumption were evaluated
      before and after FESS (mean follow-up, 74 months). An actuarial analysis using
      the Kaplan Meier life table method was performed with regard to the 3- and 5-year
      symptoms control rates. RESULTS: All symptoms were improved after FESS. The 5
      year actuarial nasal obstruction control rate was 65.8%. The 5-year actuarial
      severe posterior rhinorrhea control rate was 82.9%. The 5-year actuarial smell
      loss and anosmia control rates were 17.7% and 65.8%, respectively. Polyp volume
      and steroid consumption decreased significantly after FESS.

PMID- 17453468
TI  - Transmucosal coil migration after endovascular management for carotid artery
      pseudoaneurysm: a late complication.

PMID- 17453469
TI  - Paroxysmal positional vertigo after cochlear implantation.
AB  - CONCLUSIONS: We observed 4 cases of paroxysmal positional vertigo (PPV) among 62
      cochlear implant (CI) recipients. They occurred in the implanted ear without
      chronological relation with the surgical procedure or the implant's activation.
      All of them relapsed within 3 months after an initially successful repositioning
      maneuver, and finally recovered after the second one. None of the patients showed
      labyrinthine weakness in the implanted ear. The outbreak of PPV did not affect
      the patients' speech perception performances. OBJECTIVES: To report and discuss
      the occurrence of PPV after cochlear implantation. PATIENTS AND METHODS: Among 32
      adult patients who received a Nucleus CI, 4 suffered from PPV on the basis of Dix
      Hallpike's maneuvers. After a Semont's repositioning maneuver, recurrences were
      similarly addressed. An electro-nystagmography (ENG) recording of caloric
      irrigation tests was obtained once the symptoms subsided. RESULTS: The observed
      incidence of 12.5% exceeds the figures reported in the literature. No anatomic
      abnormalities were identified in these patients, nor were any intraoperative or
      postoperative complications reported. PPV developed 1-12 months after CI surgery
      in the posterior canal and relapsed within 3 months. ENG showed a normal
      reflectivity in two patients, while the other two had a significant prevalence of
      the implanted side. The outcomes of the speech perception tests after CI in all
      the four patients matched those of their corresponding categories.

PMID- 17453470
TI  - Differential gene expression profiles in salicylate ototoxicity of the mouse.
AB  - CONCLUSION: This study demonstrated differential gene expression profiles in
      salicylate ototoxicity with oligonucleotide microarray. This study may also
      provide basic information on candidate genes associated with hearing loss and/or
      tinnitus or recovery after salicylate-induced cochlear dysfunction. OBJECTIVES:
      Salicylate ototoxicity is accompanied by temporary hearing loss and tinnitus. The
      purpose of the present study was to evaluate the gene expression profiles in the
      mouse cochlea with salicylate ototoxicity using DNA microarray. MATERIALS AND
      METHODS: The subject mice were injected intraperitoneally with 400 mg/kg of
      sodium salicylate; an approximate 30 dB threshold shift that was observed by
      auditory brainstem response was achieved 3 h after an injection of sodium
      salicylate and the hearing threshold returned to within normal range at 3 days.
      Differential gene expression profiles at 3 h after salicylate injection in
      comparison to the normal cochlea were analyzed with DNA microarray technology.
      RESULTS: No ultrastructural changes in the mice cochlea were observed by TEM at 3
      h after salicylate injection. Microarray revealed that 87 genes were up-regulated
      twofold or more in the mouse cochlea with salicylate ototoxicity in comparison to
      the normal cochlea. Among these genes, increased expression levels of 30
      functional genes were confirmed by semi-quantitative RT-PCR.

PMID- 17453471
TI  - Prediction of gastroesophageal reflux in otitis media with effusion in adults.
AB  - CONCLUSIONS: The measurement of pepsinogen I (PGI) in middle-ear effusions (MEEs)
      and a questionnaire on the frequency symptoms of gastroesophageal reflux (GER)
      disease are tools that can be used to screen for the existence of GER. OBJECTIVE:
      To seek methods that would be beneficial as a screen for the presence of GER
      among adult patients with OME. MATERIALS AND METHODS: Fifty-eight adult
      outpatients with OME were asked to answer a questionnaire of the frequency scale
      for symptoms of GER disease. Samples of MEEs were obtained from each subject and
      were measured for concentrations of PGI and PGII. Some patients were followed up
      after being treated with a proton pump inhibitor. RESULTS: The percentage of
      patients with high PGI concentrations in their MEEs was higher in those with GER
      related symptoms than in those without GER-related symptoms. Moreover, OME was
      present bilaterally in a higher percentage of patients with GER-related symptoms.
      There were patients in whom PGI levels decreased after receiving treatment for
      GER.

PMID- 17453472
TI  - Results of hearing tests after total middle ear reconstruction.
AB  - CONCLUSIONS: Patients treated by mastoidectomy in the past often present with
      hearing loss and cavity problems such as pus discharge. Total middle ear
      reconstruction (TMER) improves the hearing of these patients by correcting cavity
      problems and resolution of ear discharge, which facilitates ossicular chain
      reconstruction such as type III or type IV tympanoplasty. OBJECTIVE: To evaluate
      the effectiveness of TMER in improving hearing. PATIENTS AND METHODS: We reviewed
      the audiograms of 56 ears of 48 patients who underwent TMER in combination with
      either type III or type IV tympanoplasty. Audiometric pure tone thresholds
      averaged over three frequencies (500, 1000, and 2000, pure tone average) were
      measured and compared before and after surgery. Successful outcome was defined as
      improvement of 15 dB or more. The mean follow-up was 5.7 years (range 1.1-12.6).
      We also analyzed the relations between hearing improvement and factors such as
      type of tympanoplasty (types III and IV), choice between one-stage and two-stage
      operation, and the interval between original mastoidectomy and final operation.
      RESULTS: The mean hearing gain was 13.6 (+/-11.9) dB. Twenty-seven procedures
      (48.2%) were considered successful, with improvement of 15 dB or more. The
      results of type III tympanoplasty group were significantly superior to those of
      type IV (p<0.05, Student's t test). One- and two-stage surgery did not
      significantly influence outcome. The interval between the initial operation
      correlated weakly and negatively (r = - 0.266, p<0.05) with hearing gain.

PMID- 17453473
TI  - Acute otitis media in schoolchildren: allergic diseases and skin prick test
      positivity.
AB  - CONCLUSIONS: Single and repeated episodes of acute otitis media (AOM) in 10-year
      old children were associated with reported allergic disease. Further, skin prick
      test (SPT)-negative children with reported asthma and allergic
      rhinoconjunctivitis had increased risk of AOM. We suggest that optimal treatment
      of allergic symptoms may have an effect on AOM in school children. OBJECTIVE: The
      objective of the study was to estimate associations between AOM, allergic
      diseases and SPT positivity in 10-year-old children. MATERIALS AND METHODS:
      Population-based cross-sectional study of 3406 10-year-old children living in
      Oslo. Main outcome measures were questionnaire-based information on AOM and
      reported physician-diagnosed allergic diseases with symptoms during the last
      year. In addition, 2657 children were skin prick tested. Logistic regression
      analyses were performed to estimate associations and control for potential
      confounders. RESULTS: One or more episodes of AOM were present in 13.8% (n=470)
      of the children; 9.7% (n=331) had single episodes, while 4.1% (n=139) had two or
      more infections. We found a statistically significant association between AOM and
      reported allergic diseases, strongest for AOM and asthma with odds ratio 2.7 (95%
      confidence interval 1.8-4.0) and 2.3 (95% confidence interval 1.3-4.3) for single
      and two or more episodes of AOM, respectively. The risk for AOM was increased in
      asthmatic SPT-negative children compared with asthmatic SPT-positive children,
      the odds ratios were 3.0 (1.7-5.4) and 1.5 (0.8-2.8), respectively. The same
      tendency was found for allergic rhinoconjunctivitis.

PMID- 17453474
TI  - Transsynaptic delivery of nanoparticles to the central auditory nervous system.
AB  - CONCLUSION: Silica nanoparticles may serve as a nonviral delivery system to the
      sensory hair cells, spiral ganglion cells within the cochlea, and the vestibular
      organ, as well as the cochlear nucleus. OBJECTIVES: At present there are no
      targeted therapeutics for inner ear disease. A variety of viral vector systems
      have been tested in the inner ear with variable efficacy but they are still not
      regarded as safe systems for inner ear delivery. Nanoparticles are a nonviral
      method of delivering a variety of macromolecules that potentially can be used for
      delivery within the auditory system. In this study, we evaluated the distribution
      and safety of nanoparticles in the inner ear. MATERIALS AND METHODS: Cy3-labeled
      silica nanoparticles were placed on the round window membrane of adult mice.
      Hearing thresholds were determined after nanoparticle delivery by auditory
      brainstem responses (ABRs). Distribution of particles was determined by
      histological evaluation of the cochlea, vestibular organs, and brain stem.
      RESULTS: Fluorescent microscopy demonstrated Cy3-labeled nanoparticles signals in
      the sensory hair cells and the spiral ganglion neurons of both the treated and
      contralateral inner ears. Additionally, the distal part of the central auditory
      pathway (dorsal cochlear nucleus, superior olivary complex) was found to be
      labeled with the Cy3-linked silica nanoparticles, indicating a retrograde axonal
      transport. No hearing loss or inflammation was noted in the treated cochlea.

PMID- 17453475
TI  - Clinical results of rehabilitation for accessory nerve palsy after radical neck
      dissection.
AB  - CONCLUSIONS: Occupational therapy significantly improves shoulder range of motion
      in patients with accessory nerve palsy after radical neck dissection, but it has
      limited effects on the associated pain. OBJECTIVE: To evaluate the outcome of
      occupational therapy rehabilitation for patients with accessory nerve palsy.
      PATIENTS AND METHODS: The occupational therapy group involved 35 shoulders of 29
      patients with accessory nerve palsy after radical neck dissection; the control
      group included 10 shoulders of 9 patients who did not receive occupational
      therapy. All patients had a malignant tumor in the head or neck that necessitated
      radical neck dissection. We collected data pertaining to resting pain, motion
      pain, and the active and passive range of motion during shoulder flexion and
      abduction. RESULTS: Occupational therapy did not adequately relieve resting or
      motion pain, but all patients achieved independence in activities of daily living
      and housekeeping activities. Although occupational therapy significantly improved
      shoulder elevation for all movements, shoulder elevation was significantly better
      for flexion than for active and passive abduction.

PMID- 17453476
TI  - Brainstem mediation of the stapedius muscle reflex in hydranencephaly.
AB  - Hydranencephaly is a rare condition in which the cerebral hemispheres are absent
      at birth and are replaced by membranous sacs in a cerebrospinal fluid-filled
      cranium. Surviving hydranencephalic patients have a functional brainstem and
      possible remnants of the cerebral cortex. This case report examines hearing
      function and the integrity of the brainstem mediated stapedius muscle reflex
      (SMR) in an adult with hydranencephaly, using middle ear impedance change
      measures. The brainstem mediated ipsilateral and cross-brainstem contralateral
      SMRs were elicited in the right ear at normal threshold levels for noise bands of
      0.25-1.0, 1.0-4.0, and 0.25-4.0 kHz (broadband), and at the sinusoidal
      frequencies of 0.5, 1.0, and 2.0 kHz. The ipsilateral and contralateral SMR decay
      rates were normal. The growth in the SMR amplitude in response to noise and pure
      tone stimuli from threshold to saturation over a 15-20 dB range was normal and
      showed essentially sigmoidal curves. The normal ipsilateral and crossed brainstem
      contralateral electrophysiological SMR in this hydranencephalic patient
      demonstrated the preservation of peripheral hearing reception and functional
      brainstem auditory afferent and efferent tracts and nuclei in the absence of
      corticofugal influence.

PMID- 17453477
TI  - Continuous improvement in Mandarin lexical tone perception as the number of
      channels increased: a simulation study of cochlear implant.
AB  - CONCLUSION: With reference to English phoneme recognition, where performance
      usually does not improve after six or eight channels in cochlear implants (CIs),
      increasing total channel numbers continuously improved perception of Mandarin
      tones. OBJECTIVE: To test our hypothesis that current CI strategies might be
      modified to improve Mandarin lexical tonal perception. MATERIALS AND METHODS:
      Lexical tonal perception tests using 48 monosyllables in Mandarin Chinese were
      conducted in 32 native Mandarin speakers with normal hearing. The performance of
      tonal perception was compared among the controlled factors, which were total
      channel number, number of channels allocated to the F0 spectrum, and whether
      there were spectral shifts in the electrode configuration. The experimental
      condition that preserves fine structure was used as a comparison. RESULTS: The
      signal processing strategy using 16 channels--which is technically possible with
      current CI devices--produced better tonal perception than those using 12 or 8
      channels. Increasing the number of fundamental channels did not improve tonal
      perception, and spectral shifts did not change tonal perception. An experimental
      condition (FiC12) that preserves the fine structure produced significantly better
      overall scores for tone perception than other experimental conditions with
      envelope strategies.

PMID- 17453478
TI  - Radiographic assessment of inverted papilloma.
AB  - CONCLUSION: Both CT and MRI defined the extent of histologically proven recurrent
      disease, although it was impossible to radiographically distinguish recurrent
      disease from postoperative scar tissue or mucoperiosteal thickening. OBJECTIVE: A
      retrospective analysis of radiographic findings of patients with known inverted
      papilloma (IP) was performed to identify those characteristics that should prompt
      preoperative biopsy in patients with polypoid nasal masses. MATERIALS AND
      METHODS: The radiologic studies from a group of 77 patients with biopsy-proven IP
      of the nasal cavity or paranasal sinuses were reviewed. Fifty-three computed
      tomography (CT) scans, 17 cases of plain sinus radiography and 7 cases of
      magnetic resonance imaging (MRI) were analyzed. RESULTS: Although no preoperative
      MRI examinations were available for comparison, CT was the most helpful study for
      evaluation of primary, nonrecurrent inverted papilloma. CT demonstrated disease
      related abnormalities in 90% of studies. The finding of frequent unilateral bony
      remodeling was demonstrated in 43% of scans. Plain sinus X-rays were abnormal in
      70% of cases of primary tumor, with all positive studies showing nonspecific
      unilateral opacification of the maxillary antrum.

PMID- 17453479
TI  - Eosinophil infiltration and activation in nasal polyposis.
AB  - Conclusions. Infiltration and activation of eosinophils is a characteristic of
      nasal polyposis. Allergic reaction is a risk factor for the accumulation of
      eosinophils in this disease. T-cell-derived interleukin 5 (IL-5) and
      autosecretion of IL-5 from activated eosinophils may be causative reasons for the
      extension and persistence of eosinophil inflammation. Objectives. To investigate
      whether eosinophils were accumulated and activated in nasal polyposis, and the
      roles of IL-5, eotaxin, and T cells in this process. Materials and methods. A
      retrospective study was conducted on 17 tissue samples from patients with nasal
      polyposis with allergy and 26 cases of non-allergic polyposis.
      Immunohistochemical staining by specific antibodies was carried out using the
      alkaline phosphatase anti-alkaline phosphatase method and the avidin-biotin
      complex technique.Results. The number of EG1-positive cells (pan eosinophil
      marker) was similar to the number of EG2-positive cells (activated eosinophil
      marker) in all tissue samples, although EG1- and EG2-positive cells were richer
      in allergic patients than those in non-allergic patients. Both EG1- and EG2
      positive cells were correlated with CD3-positive cells (pan T cell marker) and IL
      5-producing cells in allergic or non-allergic polyposis. A large proportion of IL
      5 producing cells were eosinophils. Eotaxin protein was detected in all tissue
      samples and dominantly located in epithelial cells. Eotaxin expression between
      allergic and non-allergic subjects was not significantly different.

PMID- 17453480
TI  - Soft palate implants as a minimally invasive treatment for mild to moderate
      obstructive sleep apnea.
AB  - CONCLUSION: The palatal implant method originally designed to reduce snoring can
      significantly reduce the apnea-hypopnea index (AHI) in some patients with mild to
      moderate obstructive sleep apnea (OSA) in a single office-based procedure.
      OBJECTIVE: An initial study designed to evaluate the short-term efficacy and
      safety of palatal implants as primary treatment for patients with mild to
      moderate OSA. MATERIALS AND METHODS: This was a prospective, non-randomized study
      of 16 previously untreated and undiagnosed patients with sleep apnea. The
      inclusion criteria were an AHI of 10-30/h and a body mass index (BMI) < or = 30.
      RESULTS: The mean AHI was reduced following implantation, from 16.1 to 11.8
      (p<0.01). A reduction in AHI was achieved in 13 patients (81%). Ten of 16
      patients had their AHI reduced to <10.0. Snoring intensity decreased from 8.3+/
      1.8 to 4.7+/-2.5 on a visual analog scale (p<0.001) and daytime sleepiness
      dropped from 7.2+/-2.5 to 4.6+/-3.2 on the Epworth Sleepiness Scale (p<0.05). No
      significant adverse events were reported.

PMID- 17453481
TI  - Tumour-associated macrophages secrete IL-6 and MCP-1 in head and neck squamous
      cell carcinoma tissue.
AB  - Conclusion. Tumour-associated macrophages (TAMs) in head and neck squamous cell
      carcinomas (HNSCCs) secrete interleukin 6 (IL-6) and monocyte chemotactic protein
      (MCP-1) that can be down-regulated by L-leucine-methylester (LLME); however,
      there is no qualitative difference between function of TAMs and tissue
      macrophages in mucosa as measured by IL-6 and MCP-1 secretion. Objectives. TAMs
      play an important role in the interaction with tumour cells in malignant tumours.
      The cells in the tumours that are the main sources of the various signal
      substances need to be further elucidated. The aim of this investigation was to
      reveal whether TAMs in HNSCCs secrete IL-6 and MCP-1. These cytokines influence
      tumour cell growth and macrophage influx in tumours, respectively. Materials and
      methods. In order to inhibit macrophage function in F-spheroids, in some
      experiments the tissue fragments were initially incubated with LLME, a substance
      that selectively inhibits function of phagocytes. IL-6 and MCP-1 secretion from
      untreated F-spheroids was compared to cytokine secretion from LLME-treated F
      spheroids as measured by ELISA. Results. LLME did not affect the viability of F
      spheroids and reduced IL-6 and MCP-1 secretion from monocyte-derived macrophages
      in vitro. F-spheroids from LLME-treated tissue fragments showed lower IL-6 and
      MCP-1 secretion compared with F-spheroids from tissue fragment untreated with
      LLME.

PMID- 17453482
TI  - Cell proliferation, apoptosis, and apoptosis inhibition in malignant
      transformation of sinonasal inverted papilloma.
AB  - CONCLUSION: Increasing cell proliferation seems to be a very important factor in
      the development of inverted papilloma (IP). Apoptosis that was increased but
      weakly inhibited by Bcl-2 did not cause imbalance in the cell proliferation.
      Further increased cell proliferation in IP with dysplasia was an important
      mechanism of growth in dysplastic areas. OBJECTIVES: The purpose of this study
      was to compare cell proliferation, apoptosis, and apoptosis inhibition by Bcl-2
      in IP. PATIENTS AND METHODS: Cell proliferation and apoptosis inhibition were
      detected by immunohistochemical staining with monoclonal antibodies to Ki-67 and
      Bcl-2. Apoptosis was detected by the transferase-mediated dUTP nick end-labeling
      (TUNEL) method. RESULTS: As regards the Ki-67 index (KI), a significant increase
      was observed in IP with severe dysplasia, IP with carcinoma and invasive squamous
      cell carcinoma (SCC) compared with EP and IP with mild and moderate dysplasia.
      For the apoptosis index (AI), a significant increase was observed in IP with mild
      and moderate dysplasia compared with IP with carcinoma, invasive SCC and EP. For
      the Bcl-2 index (BI), a significant increase in expression was observed in IP
      with severe dysplasia and carcinoma and invasive SCC compared with control, EP
      and IP with mild dysplasia. Among IP, the KI (average 18.2%) was much higher than
      the AI (6.4%) and BI (4.1%).

PMID- 17453483
TI  - 3D-FLAIR MRI findings in a patient with Ramsay Hunt syndrome.
AB  - Three-dimensional, fluid-attenuated inversion recovery (3D-FLAIR) of magnetic
      resonance imaging (MRI) has recently been developed to detect hemorrhage or high
      concentrations of protein. We present a patient with Ramsay Hunt syndrome, in
      whom high signals in the cochlear and vestibular apparatus were identified with
      3D-FLAIR. The high signal areas in 3D-FLAIR were not detected by T1- and T2
      weighted MRI in this case. This is the first report of high concentrations of
      protein in the inner ear in Ramsay Hunt syndrome using 3D-FLAIR, and suggests
      that high concentrations of protein in the inner ear are associated with hearing
      deterioration in some patients with Ramsay Hunt syndrome. 3D-FLAIR could be a
      useful diagnostic tool in the early stages of Ramsay Hunt syndrome.

PMID- 17453484
TI  - Actinomycosis of the larynx.
AB  - Actinomycosis is a rare chronic granulomatous disease that involves the upper
      airway and gastrointestinal tract. Approximately 40-55% of actinomycosis
      comprises the cervicofacial form. It presents a challenging clinical diagnostic
      dilemma because of variable presentations in the head and neck. Herein, we report
      a rare case of actinomycosis presenting as a vocal cord nodule in a healthy 21
      year-old man who was not immunocompromised and had no other known medical
      disease.

PMID- 17453485
TI  - Tuberculous meningitis-induced unilateral sensorineural hearing loss: a temporal
      bone study.
AB  - The relationship between meningitis and sensorineural hearing loss (SNHL) has
      long been studied. Many histopathological studies of animal models and human
      temporal bones with respect to bacterial meningitis have been carried out.
      However, the relationship between SNHL and tuberculous meningitis was seldom
      addressed and the pathophysiology remains unclear. We carried out temporal bone
      studies on material from a 22-year-old patient who developed a right unilateral
      SNHL before dying from tuberculous meningitis. The histopathological findings for
      the right temporal bone were as follows: (1) inflammation mainly appeared in the
      internal auditory canal, modiolus and Rosenthal's canal and extended to the
      osseous spiral ligament, whereas the perilymphatic spaces were less involved; (2)
      the organ of Corti, cochlear nerve fibres and spiral ganglion cells were severely
      degenerated, particularly in the basal and middle turns; (3) the contralateral
      side (for which the patient had no complaints) showed an inner space free from
      inflammation, but some granulomatous formations were observed in the middle ear
      cavity. We conclude that the modiolus and cochlear aqueduct are the main routes
      for the spread of infection from the meninges to the inner ear. The progression
      of hearing loss resembles that of bacterial meningitis and shares attributes of
      retrocochlear SNHL.

PMID- 17453486
TI  - A new reduction glossoplasty technique for macroglossia.

PMID- 17453488
TI  - Magnetic resonance elastography of brain tumors.

PMID- 17453489
TI  - Radiofrequency ablation of liver metastases improves the survival rate of
      patients with metastatic colorectal disease.

PMID- 17453490
TI  - Xenia Forsselliana 2006.

PMID- 17453491
TI  - Radiofrequency ablation of colorectal liver metastases: long-term survival.
AB  - PURPOSE: To evaluate the results of radiofrequency ablation (RFA) therapy with
      regard to long-term survival and rate of complications in patients with liver
      metastases from colorectal carcinoma. MATERIAL AND METHODS: A total of 102
      patients were included and treated with RFA. In 100 patients, resection was not
      possible; two patients refused surgery. The patients had a total of 332
      colorectal liver metastases. Pre- and post-treatment evaluation was performed
      with contrast-enhanced computed tomography. Survival from time of diagnosis of
      liver metastases was calculated by Kaplan-Meier analysis. Complications were
      recorded as minor or major in accordance with the definitions of the Society for
      Cardiovascular and Interventional Radiology. RESULTS: Estimated median survival
      from time of diagnosis of liver metastases was 52 months (95% CI 34-82).
      Estimated 1-, 2-, 3-, 4-, and 5-year survival was 96%, 79%, 64%, 52%, and 44%,
      respectively. Minor complications were recorded following seven RFA treatments
      (4.0%) and major complications following 12 RFA treatments (6.9%). CONCLUSION:
      RFA is an effective method to treat liver metastases from colorectal carcinoma.
      Survival is improved and comparable with survival following surgical resection.
      The rate of complications is low.

PMID- 17453492
TI  - Cost-effectiveness of computed tomographic colonography: a prospective comparison
      with colonoscopy.
AB  - PURPOSE: To estimate the cost-effectiveness of detecting colorectal polyps with
      computed tomographic colonography (CTC) and subsequent polypectomy with primary
      colonoscopy (CC), using CC as the alternative strategy. MATERIAL AND METHODS: A
      marginal analysis was performed regarding 103 patients who had had CTC prior to
      same-day CC at two hospitals, H-I (n = 53) and H-II (n = 50). The patients were
      randomly chosen from surveillance and symptomatic study populations (148 at H-I
      and 231 at H-II). Populations, organizations, and procedures were compared. Cost
      data on time consumption, medication, and minor equipment were collected
      prospectively, while data on salaries and major equipment were collected
      retrospectively. The effect was the (previously published) sensitivities of CTC
      and CC for detection of colorectal polyps > or = 6 mm (H-I, n = 148) or > or = 5
      mm (H-II, n = 231). RESULTS: Thirteen patients at each center had at least one
      colorectal polyp > or = 6 mm or > or = 5 mm. CTC was the cost-effective
      alternative at H-I (euro187 vs. euro211), while CC was the cost-effective
      alternative at H-II (euro239 vs. euro192). The cost-effectiveness (costs per
      finding) mainly depended on the sensitivity of CTC and CC, but the depreciation
      of equipment and the staff's use of time were highly influential as well.
      CONCLUSION: Detection of colorectal polyps > or = 6 mm or > or = 5 mm with CTC,
      followed by polypectomy by CC, can be performed cost-effectively at some
      institutions with the appropriate hardware and organization.

PMID- 17453494
TI  - Ultrasound, computed tomography, and laboratory findings in the diagnosis of
      appendicitis.
AB  - PURPOSE: To determine the diagnostic accuracy and the clinical impact of
      ultrasound (US) and computed tomography (CT) in diagnosing appendicitis, and to
      evaluate the impact of laboratory tests on the treatment of acute appendicitis.
      MATERIAL AND METHODS: All patients who, during 2005, underwent an acute
      ultrasound or CT investigation due to suspected appendicitis, or were diagnosed
      and/or surgically treated for appendicitis at Umea University Hospital, Umea,
      were included. The type of radiological investigation, its findings, the choice
      of treatment, final diagnosis, C-reactive protein (CRP), leukocyte particle count
      (LPC), body temperature, age, and sex were recorded for each patient. The
      histological result from surgery was considered the gold standard. RESULTS: The
      material included 305 cases with an overall appendicitis prevalence of 58%. Fifty
      two percent of the patients were female. The mean age was 29 years, with a total
      range of 2-94 years. Twenty percent (60/305) underwent a CT investigation, 40%
      (123/305) underwent an US investigation, 5% (14/305) underwent both a CT and an
      US investigation, and 35% (108/305) of patients did not undergo any radiological
      investigation at all. The sensitivities and specificities were 91% and 94% for
      CT, and 83% and 98% for US, respectively. The positive likelihood ratio was 15.1
      and 45.5 for CT and US, and the negative likelihood ratio was 0.09 and 0.18 for
      CT and US, respectively. It was not possible to visualize the appendix in 31% of
      patients examined with US. The prevalence of appendicitis in this group was the
      same as the prevalence among patients where it was possible to see the appendix,
      i.e., 35%. The mean CRP for all patients with appendicitis was 59 (95% CI 10-491)
      mg/l, and the mean LPC was 11.1 (95% CI 2.6-28.1) x10(-9)/l. The mean LPC level
      was significantly higher for the appendicitis patients. Body temperature could
      not significantly verify or exclude appendicitis. The overall negative
      appendectomy rate was 9% (16/176), and it was higher in women, i.e., 11% (9/79).
      The negative appendectomy rate was slightly higher in the group that was examined
      by CT and/or US, i.e., 12% (8/69) compared to 7% (8/107) in the group not
      examined radiologically. CONCLUSION: Diagnostic accuracy was high for US as well
      as for CT. US was better for diagnosing positive findings, while CT was better
      for excluding diagnosis of appendicitis. The diagnostic accuracy of LPC, CRP, and
      body temperature was low. By combining findings from the radiological examination
      with the results from the clinical examination and laboratory values, a low
      negative appendectomy rate can be achieved.

PMID- 17453495
TI  - Renal artery aneurysm: diagnosis and surveillance with multidetector-row computed
      tomography.
AB  - PURPOSE: To investigate the prevalence of renal artery aneurysms, and to assess
      the value of multidetector-row computed tomography (MDCT) in diagnosing renal
      artery aneurysms. MATERIAL AND METHODS: Altogether, 862 patients underwent
      arterial-phase contrast-enhanced CT scan of the abdomen in the period November
      2003 to October 2005. A search for renal artery aneurysms was performed in our
      reporting system and revealed six patients with renal artery aneurysm (RAA).
      RESULTS: The incidence of RAA was 0.7%. All renal artery aneurysms were solitary,
      located in the main trunk or the first branch of the renal artery, with sizes
      from 1.5 cm to 3.4 cm. Five aneurysms were saccular, one fusiform. No underlying
      thrombosis was seen. Extensive calcification was found in one aneurysm. Three
      aneurysms were diagnosed using axial images, while three aneurysms were only
      displayed by volume rendering and maximum-intensity projection images.
      CONCLUSION: This study demonstrates a 0.7% incidence of renal artery aneurysms in
      a total of 862 patients. MDCT has an important role in detecting and assessing
      renal artery aneurysms. Some aneurysms can only be displayed by post-processing
      techniques such as volume rendering and maximum-intensity projection.

PMID- 17453496
TI  - Embolization of accessory left gastric artery to prevent acute gastric mucosal
      lesions in patients undergoing repeated hepatic arterial infusion chemotherapy.
AB  - PURPOSE: To retrospectively evaluate results of selective embolization of the
      accessory left gastric artery prior to repeated hepatic arterial infusion
      chemotherapy using a port-catheter system. MATERIAL AND METHODS: Of 22 patients
      with unresectable advanced liver cancer who underwent percutaneous implantation
      of a port-catheter system, an accessory left gastric artery was revealed by
      arteriography in 16 patients before and in six patients after port-catheter
      implantation. The right gastric artery was embolized to prevent gastric mucosal
      lesions in all 22 patients. In addition, the accessory left gastric artery was
      selectively embolized for the same purpose using from one to six microcoils,
      which were from 3 to 5 mm in diameter. Within 10 days after implantation,
      arteriography was performed while contrast material was infused via the port.
      RESULTS: Selective embolization of the accessory left gastric artery was
      successful in all 22 patients. No complication related to embolization of this
      artery occurred in any patient. A gastrointestinal mucosal lesion developed in
      only one case during hepatic arterial infusion chemotherapy, but was unrelated to
      the accessory left gastric artery. CONCLUSION: Prophylactic embolization of the
      accessory left gastric artery is useful to avoid development of a
      gastrointestinal mucosal lesion resulting from hepatic arterial infusion
      chemotherapy.

PMID- 17453498
TI  - The exactness of left ventricular segmentation in cine magnetic resonance imaging
      and its impact on systolic function values.
AB  - PURPOSE: To evaluate the impact of exactness of the segmentation of the left
      ventricle (LV), using cine magnetic resonance imaging (MRI). MATERIAL AND
      METHODS: Steady-state free-precession cine MRI was performed on 100 randomly
      selected subjects. Myocardial borders were outlined on short-axis images using
      three methods: method 1 was computer assisted, excluding papillary muscles from
      the left ventricular mass (LVM); method 2 was similar but included papillary
      muscles; and method 3 was manually traced including papillary muscles. LV end
      systolic (ES) and end-diastolic (ED) masses and volumes, ejection fraction (EF),
      stroke volume (SV), and cardiac output (CO) were calculated from these
      measurements. The difference between the ES and ED LVM was used to estimate the
      exactness of the methods. RESULTS: Method 3 was the most exact, and method 1 was
      the least exact. The three methods generated differing EF, SV, and CO
      measurements. With an ES-ED LVM difference exceeding 20 g, the mean SV
      measurement error was 8.8+/-3.6 ml. CONCLUSION: Manual tracing proved more exact
      than computer-assisted quantification. Exactness had an impact on EF, SV, and CO
      measurements, and the ES-ED LVM difference can be used to identify assessments
      that would benefit from more exact segmentation.

PMID- 17453499
TI  - Influence of radiographic contrast media on myocardial oxygen tension: a
      randomized, NaCl-controlled comparative study of iodixanol versus iomeprol in
      pigs.
AB  - PURPOSE: To examine how a one-time bolus injection of radiographic contrast media
      (RCM; iodixanol 320 and iomeprol 350) into the left coronary artery of six pigs
      affects tissue oxygen tension in the artery's supply area (pO(2 )LAD) compared to
      a 0.9% sodium-chloride (NaCl) bolus. MATERIAL AND METHODS: Each animal received a
      total of three boluses: one iodixanol, one iomeprol, and one NaCl (10 ml each).
      The radiographic contrast media and NaCl boluses were randomly assigned, and
      pO(2) profiles were recorded. RESULTS: 26.7+/-16.4 s after iodixanol injection,
      pO(2) LAD had declined by 3.5% from 42.2+/-5.6 mmHg to 40.7+/-5.9 mmHg (P =
      0.0357). After 53+/-16.7 s, the initial value was restored. The pO(2) LAD was
      41.9+/-7.4 mmHg before iomeprol injection, and, 303.3+/-58.9 s after injection,
      pO(2) LAD had declined by 13.1% to 36.4+/-7.5 mmHg (P = 0.0001). After 577+/-22
      s, the initial value was restored. The bolus application of an isotonic NaCl
      solution resulted in no effect on pO(2) LAD. Immediately after injection, it
      increased by 3%. In the supply area of the right coronary artery and the
      peripheral skeletal muscle, no effect of the RCM or NaCl on tissue oxygen tension
      was observed. Furthermore, no effect on tissue temperature, heart rate, systolic
      and diastolic blood pressure, or cardiac output per minute occurred. CONCLUSION:
      The injection of RCM in a coronary artery can result in a significant local
      contrast-medium-induced microcirculation disorder. The high viscosity of
      iodixanol led to a very short-term insignificant effect on the microcirculation,
      while iomeprol induced a slight time-delayed pO(2) decrease, which might be
      caused by the rigidification of erythrocytes. In comparison to a previous study
      with iopromide, the influence of iodixanol and iomeprol on myocardial oxygen
      tension was markedly less pronounced.

PMID- 17453500
TI  - Noninvasive coronary angiography using 64-detector-row computed tomography in
      patients with a low to moderate pretest probability of significant coronary
      artery disease.
AB  - PURPOSE: To evaluate the value of 64-detector-row computed tomography for ruling
      out high-grade coronary stenoses in patients with a low to moderate pretest
      probability of significant coronary artery disease. MATERIAL AND METHODS: The
      study included 61 patients with a suspicion of coronary artery disease on the
      basis of atypical angina or ambiguous findings in noninvasive stress testing and
      a class II indication for invasive coronary angiography (ICA). All patients were
      examined by 64-detector-row computed tomography angiography (CTA) and ICA. On a
      coronary segmental level, the presence of significant (> or = 50% diameter)
      stenoses was examined. RESULTS: In a total of 915 segments, CTA detected 62
      significant stenoses. Thirty-four significant stenoses were confirmed by ICA,
      whereas 28 stenoses could not be confirmed by ICA. Twenty-two of them showed wall
      irregularities on ICA, and six were angiographically normal. Accordingly, on a
      coronary segmental basis, 28 false-positive and 0 false-negative findings
      resulted in a sensitivity of 100%, a specificity of 96.8%, a positive predictive
      value of 54.8%, and a negative predictive value of 100%. The diagnostic accuracy
      was 96.9%. CONCLUSION: Sixty-four-detector-row computed tomography reliably
      detects significant coronary stenoses in patients with suspected coronary artery
      disease and appears to be helpful in the selection of patients who need to
      undergo ICA. Calcified and non-calcified plaques are detected. Grading of
      stenoses in areas with calcification is difficult. Frequently, stenosis severity
      is overestimated by 64-detector-row computed tomography.

PMID- 17453502
TI  - Magnetic resonance imaging of the femoral neck cortex.
AB  - PURPOSE: To determine the in vivo precision and accuracy of magnetic resonance
      imaging (MRI) in evaluating the thin (approximately mm) femoral neck cortex.
      MATERIAL AND METHODS: Hip regions of 30 volunteers were scanned with standard 1.5
      T MRI twice with repositioning, and the images of the narrow-neck cross-sections
      were obtained. Two radiologists independently delineated periosteal and endosteal
      cortical boundaries, and several structural variables were determined. For
      precision, 95% limits of agreement and coefficients of variation were calculated.
      Accuracy was determined with phantoms. RESULTS: In vivo precision of the directly
      delineated measurements varied from 0.9% (periosteal circumference) to 1.6%
      (total area), while the precision of the calculated variables remained poorer,
      from 7.3% (cortical to total area ratio) to 15.1% (torsional rigidity). The root
      mean-square error of the cortical thickness measurement was 0.15 mm. CONCLUSION:
      Thin cortical bone at the narrowest location of the femoral neck can be
      delineated precisely and accurately with a standard clinical 1.5 T MRI device.
      MRI provides a feasible tool for the assessment of mechanically important
      cortical bone at the femoral neck and may be of clinical utility in assessing hip
      fragility.

PMID- 17453503
TI  - Vertebroplasty: magnetic resonance findings related to cement leakage risk.
AB  - PURPOSE: To find magnetic resonance (MR) findings predicting cement leakage in
      patients receiving percutaneous vertebroplasty (PVP) due to osteoporotic
      compression fractures. MATERIAL AND METHODS: MR was done in 43 patients (age 52
      89 years) before PVP (56 vertebrae), which was done via a bipedicular approach
      with fluoroscopic monitoring. Shortly after the procedure, a non-contrast
      enhanced computed tomography (CT) scan was done at the vertebroplasty sites for
      evaluation of bone cement leakage. The following MR findings of fractured
      vertebral bodies were retrospectively reviewed for correlation with leakage risk:
      severity of bone-marrow edema, presence of a T2-weighted low-signal-intensity
      line, percentage residual vertebral body height, presence of either a vacuum or
      cystic change within the vertebral body, and presence of a cortical disruption.
      RESULTS: After PVP, cement leakage was detected in 35 vertebrae (62.5%). Leakage
      was most frequently observed in the anterior external vertebral venous plexus
      (46%). Cement leakage rate increased when there was a cortical disruption (P =
      0.037), especially at the endplates, while it decreased when there was a vacuum
      or a cystic change within the fractured vertebra (P = 0.019). Other MR findings
      were not related to the risk of cement leakage. CONCLUSION: The risk of cement
      leakage in PVP increases when MR shows cortical disruption in a fractured
      vertebral body, especially at the endplates. It decreases when MR shows a vacuum
      or cystic change within the body.

PMID- 17453504
TI  - Preoperative embolization of lower-falx meningiomas with ethylene vinyl alcohol
      copolymer: technical and anatomical aspects.
AB  - PURPOSE: To report the feasibility of using ethylene vinyl alcohol copolymer
      (EVAC) for embolization of lower-falx meningiomas. MATERIAL AND METHODS: Three
      patients were treated. The procedures were done under general anesthesia. A
      terminal branch of the middle cerebral artery in the proximity of the tumor was
      catheterized as near as possible or into the pre-falcine arterial anastomotic
      network around the superior sagittal sinus, and embolization with EVAC was
      performed with a standard injection technique. RESULTS: This technique resulted
      in filling of the tumor-supplying dural arteries including all collaterals from
      both sides, filling of the dural territory of the tumor circulation, and some
      obliteration of the tumor's pial supply. On later operation, the tumors could be
      removed from the inside out with minimal brain retraction. CONCLUSION: Effective
      preoperative embolization of lower-falx meningiomas using EVAC is feasible. This
      technique has a sound anatomical basis, and it can be used with benefit even in
      falx meningiomas with predominantly pial vascular supply.

PMID- 17453505
TI  - Magnetic resonance elastography of brain tumors: preliminary results.
AB  - PURPOSE: To investigate the potential value of magnetic resonance elastography
      (MRE) in evaluating the consistency of brain tumors. MATERIAL AND METHODS: Six
      patients with known solid brain tumor underwent brain MRE studies. Consistency of
      brain tumors was evaluated at surgery. Correspondence of MRE evaluation with
      operative result was studied. RESULTS: The elasticity of tumors in six patients
      evaluated by MRE agreed with the tumor consistency given by the operative
      results. CONCLUSION: MRE could be used as an imaging technique for noninvasive
      assessment of the consistency of brain tumor in vivo.

PMID- 17453506
TI  - Rosai-Dorfman disease with epidural and spinal bone marrow involvement: magnetic
      resonance imaging and diffusion-weighted imaging features.
AB  - Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman
      disease, is a rare histiocytic disorder that typically presents with chronic,
      self-limiting cervical lymphadenopathy. Although this disease mainly affects
      histiocytes, there are a few reports of bone marrow infiltration. Diffusion
      weighted imaging (DWI) is a promising technology in differentiating between
      various bone marrow pathologies. We here present conventional magnetic resonance
      imaging and DWI features of a patient with SHML and bone marrow involvement.

PMID- 17453507
TI  - Dynamic susceptibility contrast perfusion magnetic resonance imaging in patients
      with symptomatic unilateral middle cerebral artery stenosis or occlusion.
AB  - PURPOSE: To evaluate cerebral hemodynamic disturbance in patients with
      symptomatic unilateral middle cerebral artery (MCA) high-grade stenosis or
      occlusion using dynamic susceptibility contrast perfusion magnetic resonance
      imaging (DSC-pMRI). MATERIAL AND METHODS: DSC-pMRI was performed in 28 patients
      with symptomatic unilateral MCA high-grade stenosis or occlusion. Hemodynamic
      parameters including relative cerebral blood flow (rCBF), relative cerebral blood
      volume (rCBV), relative mean transit time (rMTT), and time to peak (TTP) were
      calculated and compared between the stenosed or occluded side and contralateral
      side. Seven of the 28 patients underwent surgery or interventional therapy, and
      hemodynamic changes between pre- and post-therapy were investigated. RESULTS:
      Prolonged rMTT and TTP were found in the stenosed or occluded MCA territories in
      all 28 patients. Significant differences were found in rCBV (P<0.05), rMTT
      (P<0.001), and TTP (P<0.001) between the stenosed or occluded side and the
      contralateral side. However, no significant difference was observed in rCBF
      (P>0.05). In the seven patients with surgical or interventional therapy, the
      values of rMTT and TTP significantly decreased after surgery or interventional
      therapy (P<0.001). CONCLUSION: DSC-pMRI may be a useful tool for evaluating and
      monitoring cerebral hemodynamic disturbance in patients with symptomatic
      unilateral MCA high-grade stenosis or occlusion.

PMID- 17453508
TI  - Detection of early vessel leakiness in acute ischemic stroke using computed
      tomography perfusion may indicate hemorrhagic transformation.
AB  - This short communication presents significantly increased permeability in two
      patients with acute stroke, indicating an early blood-brain barrier disruption.
      Neither of the patients had undergone any thrombolytic therapy and hemorrhaged
      later. Increased permeability was assessed in both patients using a distributed
      parameter model of capillary-tissue exchange. Our findings indicate that early
      physiologic imaging in stroke may identify patients with a high risk of
      hemorrhagic transformation by revealing pathologic vascular changes and, thus,
      guide therapeutic options.

PMID- 17453509
TI  - Radiological findings and their clinical correlations in nephropathia epidemica.
AB  - Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal
      syndrome (HFRS). Its course varies from asymptomatic to fatal. The etiologic
      agent, Puumala virus, belongs to the Hantavirus genus of the Bunyaviridae family.
      Respiratory symptoms, from common cold to respiratory distress, occur in NE.
      Acute renal failure (ARF) is evident in over 90% of hospital-treated NE patients.
      In this review article, special attention is paid to radiological lung and renal
      involvement to investigate the occurrence and type of manifestations during the
      acute phase of infection and recovery.

PMID- 17453510
TI  - Superselective arterial embolization for patients with high-flow priapism:
      results of follow-up for five or more years.
AB  - PURPOSE: To retrospectively evaluate the long-term results of transcatheter
      arterial embolization for high-flow priapism. MATERIAL AND METHODS: The study
      comprised six patients with high-flow priapism treated by superselective
      embolization of the internal pudendal arteries at our institution. The cause of
      priapism was traumatic in five patients and idiopathic in one. Follow-up was > or
      = 5 years in all cases. RESULTS: A total of nine embolizations were performed in
      the six patients. Embolization was performed once in three patients, while
      repeated embolizations were performed in the remaining three. Eleven arteries
      were altogether treated. Embolic materials used were gelatin sponge in nine
      arteries, gelatin sponge and microcoils in one, and microcoils alone in one.
      Embolization of the internal pudendal arteries on both sides in one single
      session was performed in one patient. In one patient, complete occlusion of the
      pseudoaneurysm was not achieved. However, restoration of erectile function and
      detumescence were noted during follow-up. Complications during the procedure were
      not registered. At follow-up > or = 5 years after successful embolization, all
      six patients experienced detumescence as well as normal erectile function.
      CONCLUSION: Superselective embolization of the internal pudendal artery is the
      procedure of choice for treatment of high-flow priapism.

PMID- 17453511
TI  - Retroaortic left renal vein: multidetector computed tomography angiography
      findings and its clinical importance.
AB  - PURPOSE: To evaluate the appearance, type, frequency, and clinical importance of
      retroaortic left renal vein (RLRV) in patients examined with multidetector
      computed tomography (MDCT) angiography. MATERIALS AND METHODS: A total of 1856
      patients who underwent CT with urological symptoms (hematuria, flank and
      abdominal pain, left gonadal vein varicocele) (n = 889) or with symptoms other
      than urological ones (n = 967) were prospectively evaluated for the presence of
      RLRV. CT was performed with 110 ml of iodinated contrast material through the
      antecubital vein at a rate of 3.5 ml/s. Late arterial and early venous phase
      volumetric data sets were acquired at 30 and 65 s, respectively, from the start
      of the intravenous injection of contrast medium. In addition to axial images,
      multiplanar reconstructions (MPR), maximum-intensity projection (MIP), and three
      dimensional volume-rendering (3D VR) images were used to assess left renal vein
      anomalies. Left renal vein anomalies were classified into four types according to
      their appearance: I) RLRV joining the inferior vena cava (IVC) in the orthotopic
      position; II) RLRV joining the IVC at level L4-L5; III) circumaortic or collar
      left renal vein; IV) RLRV joining the left common iliac vein. RESULTS: RLRV was
      detected in 68 (3.6%) of the 1856 patients, with 26, 22, 17, and three of types
      I, II, III, and IV, respectively. Forty-four of the 68 patients with RLRV (65%)
      were in the group with urological symptoms, while 24 patients (35%) were in the
      group without urological symptoms. Compression of the RLRV was found in 16
      patients in the urological symptoms group, while compression was detected in only
      three patients in the other group. This difference was statistically significant
      (P<0.05). The most common urological symptom was hematuria. The frequency of
      urological symptoms was higher in groups II and IV compared to the other groups.
      CONCLUSION: MDCT angiography with axial, MPR, MIP, and 3D VR images is effective
      in the detection of vascular renal anomalies such as RLRV. Diagnosing RLRV and
      differentiating it from other pathologic conditions causing hematuria is
      important in order to avoid complications during retroperitoneal surgery or
      interventional procedures.

PMID- 17453512
TI  - Detection of liver metastasis: modality of choice?

PMID- 17453513
TI  - Contrast-enhanced magnetic resonance cholangiography with Gd-BOPTA and Gd-EOB
      DTPA in healthy subjects.
AB  - PURPOSE: To evaluate the biliary enhancement dynamics of the two gadolinium
      chelates Gd-BOPTA (MultiHance) and Gd-EOB-DTPA (Primovist) in normal healthy
      subjects. MATERIAL AND METHODS: Ten healthy volunteers were evaluated with both
      agents by magnetic resonance (MR) imaging at 1.5T using a breath-hold gradient
      echo T1-weighted VIBE sequence. The relative signal intensity (SI) differences
      between the common hepatic duct (CHD) and liver parenchyma were measured before
      and 10, 20, 30, 40, 130, 240, and 300 min after contrast medium injection.
      RESULTS: Biliary enhancement was obvious 10 min post-injection for Gd-EOB-DTPA
      and was noted at 20 min for Gd-BOPTA. At 40 min delay, Gd-BOPTA reached its peak
      biliary enhancement, but at neither 30 nor 40 min delay was there any significant
      difference compared with that of Gd-EOB-DTPA. At later delays, the contrast
      between CHD and liver continued to increase for Gd-EOB-DTPA, whereas it decreased
      for Gd-BOPTA. CONCLUSION: The earlier onset and longer duration of a high
      contrast between CHD and liver for Gd-EOB-DTPA facilitates examination of
      hepatobiliary excretion. Therefore, Gd-EOB-DTPA may provide adequate
      hepatobiliary imaging within a shorter time span than Gd-BOPTA and facilitate
      scheduling at the MR unit. Further studies in patients are required to compare
      the imaging advantages of Gd-EOB-DTPA and Gd-BOPTA in clinical practice.

PMID- 17453514
TI  - Contrast-enhanced FDG-PET/CT vs. SPIO-enhanced MRI vs. FDG-PET vs. CT in patients
      with liver metastases from colorectal cancer: a prospective study with
      intraoperative confirmation.
AB  - BACKGROUND: The choice of imaging before liver surgery is debated regarding the
      use of magnetic resonance (MR) imaging, computed tomography (CT), and positron
      emission tomography (PET). No studies have compared contrast-enhanced PET/CT with
      superparamagnetic iron oxide (SPIO)-enhanced MR imaging. PURPOSE: To compare
      PET/CT with superparamagnetic iron oxide (SPIO)-enhanced MR imaging, PET, and CT
      in the detection of liver metastases (LM) and extrahepatic tumor from colorectal
      cancer (CRC). MATERIAL AND METHODS: Thirty-five patients with suspected LM
      underwent PET/CT with a contrast-enhanced CT protocol and SPIO-enhanced MR
      imaging. Readers independently analyzed images from MR imaging, PET/CT, and the
      CT part and PET part of the PET/CT study. Imaging findings were compared with
      surgical and histological findings. RESULTS: Lesion-by-lesion sensitivity and
      accuracy for liver lesions was 54% and 77% for PET alone, 66% and 83% for PET/CT,
      82% and 82% for SPIO-enhanced MR imaging, and 89% and 77% for CT alone,
      respectively. CT and SPIO-enhanced MR imaging were less specific but
      significantly more sensitive than PET (P<0.0001). For extrahepatic tumor,
      sensitivity and specificity was 83% and 96% for PET/CT and 58% and 87% for CT,
      respectively. CONCLUSION: CT and SPIO-enhanced MR imaging are more sensitive but
      less specific than PET in the detection of LM. PET/CT can detect more patients
      with extrahepatic tumor than CT alone.

PMID- 17453515
TI  - Magnetic resonance imaging in suspected rectal cancer: determining tumor
      localization, stage, and sphincter-saving resectability at 3-Tesla-sustained high
      resolution.
AB  - PURPOSE: To assess image quality and overall accuracy of 3-Tesla (3T)-sustained
      high-resolution magnetic resonance (MR) imaging for diagnostic preoperative
      workup in suspected rectal carcinoma. MATERIAL AND METHODS: Twenty-three patients
      with suspected rectal cancer underwent unenhanced and contrast-enhanced fat
      suppressed pelvic high-resolution MR imaging using a four-channel phased-array
      pelvic coil at 3T. Image quality, tumor stage, distance from the anorectal
      margin, and sphincter-saving resectability were prospectively assessed by two
      blinded readers. The results were correlated with clinical, surgical, and
      histopathologic findings. RESULTS: In all 23 patients, MR images were of
      diagnostic quality, and malignancy was correctly identified in 21 patients. The
      accuracy for determining sphincter-saving resectability was 100% (19/19). T stage
      and N stage were correctly diagnosed in 95% and 91%, respectively. MRI allowed
      correct identification of tumor extension and its relation to surgically relevant
      pelvic structures including the anorectal margin and mesorectal fascia.
      Transverse T2-weighted fast spin-echo images compared superiorly to all other
      sequences for the diagnosis of mesorectal infiltration and lymph node
      involvement. Moreover, transverse fat-suppressed contrast-enhanced T1-weighted
      images were valuable for identifying tumor infiltration, while sagittal sections
      were useful for the detection of longitudinal tumor extension. CONCLUSION: MR
      imaging with phased-array receiver coils at 3T facilitated both visualization of
      different pathologic conditions of the rectum and accurate determination of tumor
      stage in rectal carcinomas. Thus, this noninvasive diagnostic approach appeared
      highly suitable for the assessment of patients with suspected rectal carcinoma.

PMID- 17453516
TI  - Percutaneous thrombin embolization of a hepatic artery mycotic aneurysm.

PMID- 17453518
TI  - Mammographic features of local recurrence after conservative surgery and
      radiation therapy: comparison with that of the primary tumor.
AB  - PURPOSE: To compare the mammographic features of recurrent breast cancer with
      those of the primary tumor and to determine whether certain mammographic features
      are associated with a higher risk of local recurrence after breast-conserving
      therapy. MATERIAL AND METHODS: A retrospective review of mammograms of 421
      patients who were treated with conservative surgery and radiotherapy revealed 41
      recurrent tumors. Mammographic findings, location, and histopathologic
      characteristics were retrospectively compared between primary and recurrent
      tumors. RESULTS: Recurrent tumors were similar in mammographic appearance to
      primary tumors in 27 (66%) cases. Of 27 primary tumors that occurred as masses
      without calcifications, 19 (70%) recurred as a mass, and of the six isolated
      calcifications, five (83%) recurred with calcifications. Ten (53%) of the 19
      recurrent masses and five (100%) of the five recurrent calcifications had
      morphologic features that were similar to those of the primary tumor. Ninety-two
      percent (11/12) of the recurrences containing microcalcifications (isolated or
      associated with a mass) had microcalcifications in their primary tumor. Of 27
      masses that recurred, the morphology of the primary tumor was obscured in 13
      (48%), ill defined in 10 (37%), and spiculated in four (15%) of the masses.
      Seventy-six percent (31/41) of recurrences were within the lumpectomy quadrant.
      In 25 (61%) cases, the histologic findings from the primary tumor and the
      recurrence were identical. CONCLUSION: The majority of recurrent tumors appear to
      be mammographically similar to primary tumors. Therefore, it is important to
      review preoperative mammograms during follow-up of these patients. Although the
      study population is small, it was noted that mass with spiculated contour is
      associated with a lower risk for local recurrence.

PMID- 17453519
TI  - Bilateral severe mammary duct ectasia.
AB  - We present the imaging findings of severe bilateral mammary duct ectasia in a
      postmenopausal woman. Mammographic, ultrasonographic, and magnetic resonance
      findings are described. Needle biopsy was used to confirm the diagnosis.
      Etiology, clinical significance, and management strategies for this lesion are
      discussed.

PMID- 17453520
TI  - Traumatic lumbar artery arteriovenous fistula: preclinically detected by 16
      multidetector-row computed tomography and post-processing techniques.
AB  - We report a 21-year-old woman with a penetrating abdominal wound. Injuries of the
      abdominal aorta and alimentary tract were found during emergency surgery. The
      patient had a follow-up computed tomography (CT) scan 3 months after surgery.
      Arterial-phase 16-row multidetector computed tomography (MDCT) showed a
      suspicious dilated vessel adjacent to the repaired aorta on 5-mm transverse
      images. A fistula between a lumbar artery and the inferior vena cava was clearly
      demonstrated on images reformatted with two- (2D) and three-dimensional (3D)
      techniques. The patient suffered from symptoms of high-output heart failure 8
      months after surgery.

PMID- 17453521
TI  - Lung cancer detection with low-dose spiral computed tomography in chronic
      obstructive pulmonary disease patients.
AB  - PURPOSE: To determine whether low-dose spiral computed tomography (LDCT) can
      improve the lung cancer detection rate in chronic obstructive pulmonary disease
      (COPD) subjects. MATERIAL AND METHODS: From October 1999 to December 2003, 374
      COPD patients underwent LDCT for lung carcinoma screening. All subjects with an
      abnormal baseline CT scan were followed with serial CT scans as part of our
      protocol. Follow-up was continued until the demonstration of no change over a
      minimum of 24 months, or resolution. Sputum samples were also obtained for
      cytological analysis. RESULTS: On the baseline spiral CT scan, 132 of 374
      patients (35.2%) had at least one non-calcified nodule that required periodic
      follow-up with CT scans. The median follow-up time was 21 months (range 2-48
      months). Of the 374 COPD subjects, nine patients with primary lung cancer (2.4%)
      were detected: six were squamous cell carcinomas, two were small-cell lung
      carcinomas (SCLC), and one was adenosquamous carcinoma. Three of the nine tumors
      were in stage IA, two in stage IIB, two in stage IIIA, and two were limited SCLC.
      Potentially curative pulmonary resection was performed in four patients,
      pulmonary lobectomy in three, and wedge excision in one. One subject with stage
      IA squamous cell carcinoma received radiotherapy, as pulmonary function was
      severely impaired. In addition, four patients underwent removal of benign
      lesions. Sputum was collected in 205 (54.8%) of 374 patients. There were 154 (75
      %) metaplasia, 14 (6%) moderate dysplasia, and one (0.4%) malignant case.
      CONCLUSION: LDCT increases early lung carcinoma detection rate in COPD patients,
      but pulmonary function impairment may reduce its benefit.

PMID- 17453522
TI  - Differentiation between the two types of amiodarone-associated thyrotoxicosis
      using duplex and amplitude Doppler sonography.
AB  - PURPOSE: To evaluate the usefulness of Doppler parameters in the differentiation
      between the two types of amiodarone-associated thyrotoxicosis (AAT). MATERIAL AND
      METHODS: One hundred thirty-seven individuals were selected at our institution.
      They were divided into four groups: 84 normal subjects (N), 30 euthyroids taking
      amiodarone (A), 14 AAT type 1 patients (AAT1), and nine AAT type 2 patients
      (AAT2). Each AAT type was classified according to (131)I uptake and clinical
      outcome. Blindly, the resistance and pulsatility indexes (RI, PI), systolic peak
      velocity, and color pixel density (CPD) were calculated. RESULTS: AAT1 had
      greater CPD than AAT2 (P = 0.02). The latter group had similar vascularization to
      the N and A groups (P = 0.45). The area under the receiver operating
      characteristic (ROC) curve showed that systolic peak velocity in the inferior
      thyroid arteries and CPD were the best parameters in the differentiation between
      AAT type 1 and AAT type 2 (Az = 0.83 and 0.84, respectively). Impedance indexes
      were useless. CONCLUSION: Our results demonstrate that objective tests such as
      systolic peak velocities in the thyroid arteries and CPD are reliable parameters
      for differentiating between the two types of AAT.

PMID- 17453524
TI  - Correlation of femoral artery flow velocity waveform with ipsilateral iliac
      artery stenoses assessed with magnetic resonance imaging.
AB  - BACKGROUND: Magnetic resonance (MR) permits quantitative flow velocity
      measurements that could be used to detect changes in the curve profile downstream
      of a high-grade stenosis. PURPOSE: To assess whether MR flow measurements can be
      used to detect iliac artery stenoses. MATERIAL AND METHODS: Contrast-enhanced
      magnetic resonance angiography (MRA) and quantitative flow measurements in the
      lower aorta and proximal femoral arteries were performed in 29 patients with
      suspected iliac artery stenoses. Stenoses were graded into five degrees: 0%, 1
      49%, 50-74%, 75-99%, and 100% diameter reduction. The femoral artery waveforms
      were evaluated qualitatively by two independent reviewers regarding peak systolic
      velocity (PSV), aortofemoral difference in time-to-peak (DeltaTTP), systolic
      acceleration (SA), curve-shape index (CSI), and the presence of an early
      diastolic flow reversal. The correlation between these parameters and the degree
      of stenosis was assessed. RESULTS: A significant correlation with degree of
      stenosis was observed for the qualitative flow waveform evaluations, with a high
      degree of interobserver agreement (kappa = 0.84). A significant correlation was
      also found between degree of stenosis and PSV, DeltaTTP, SA, CSI, and presence of
      diastolic flow reversal. The flow velocity pattern, however, remained unchanged,
      both qualitatively and quantitatively, up to a stenosis degree of at least 75%.
      CONCLUSION: Iliac artery stenoses cause femoral artery flow waveform changes that
      can be detected with MRI, but only at high-grade levels.

PMID- 17453525
TI  - Do contrast media (iomeprol, gadopentetate dimeglumine) deteriorate
      ischemia/reperfusion injury of the liver?
AB  - BACKGROUND: Hepatic microcirculation is a main determinant of reperfusion injury
      and graft quality in liver transplantation. One of the important diagnostic
      procedures to recognize reperfusion failure is contrast-enhanced computed
      tomography or magnetic resonance imaging. PURPOSE: To examine the additional
      effect of contrast media (iomeprol and gadopentetate dimeglumine) on hepatic
      microcirculation and hepatic cellular damage in the phase of early
      ischemia/reperfusion injury of the rat liver. MATERIAL AND METHODS: The partial
      warm ischemia-reperfusion injury model of rat liver was used. Microcirculation
      and leukocyte-endothelium interaction were measured by intravital microscopy.
      Hepatic cellular damage was indicated by liver enzyme activity in the sera. The
      evaluation parameters were measured at baseline and at 30, 60, and 90 min after
      reperfusion. The contrast media (iomeprol group, n = 6; gadopentetate dimeglumine
      group, n = 6) or Ringer's solution (control group, n = 8) were applied after 30
      min of reperfusion. RESULTS: No additional injury to the ischemia/reperfusion
      injury of the liver after intravenous application of radiographic contrast media
      was found. Some protective effect was even recorded after application of
      iodinated contrast media. CONCLUSION: The use of contrast media during diagnostic
      procedure of the liver seems to be relatively safe, even in the stage of early
      reperfusion after liver transplantation.

PMID- 17453526
TI  - Creatine depletion and altered fatty acid metabolism in diseased human hearts:
      clinical investigation using 1H magnetic resonance spectroscopy and 123I BMIPP
      myocardial scintigraphy.
AB  - BACKGROUND: In the heart, the creatine kinase system plays an important role in
      energy reserves, and myocardial energy production essentially depends upon fatty
      acid metabolism. PURPOSE: To examine myocardial creatine (CR) concentration and
      altered cardiac fatty acid metabolism in various forms of heart disease. MATERIAL
      AND METHODS: Myocardial CR concentration of the septum was measured by gated 1H
      magnetic resonance spectroscopy (MRS), applying a point-resolved spectroscopy
      (PRESS) sequence in 34 patients with heart disease. Of these patients, 14
      underwent 123I BMIPP (radioactive fatty acid analogue) myocardial scintigraphy to
      evaluate myocardial fatty acid metabolism. Cardiac 123I BMIPP uptake was
      calculated as the heart-to-mediastinum count ratio. RESULTS: Myocardial CR
      concentration correlated positively with the left ventricular ejection fraction
      (LVEF) by echocardiography (R = 0.61, P<0.001, n = 34), suggesting that the
      degree of reduced CR is related to the severity of contractile dysfunction.
      Cardiac 123I BMIPP uptake also correlated positively with LVEF (initial image, R
      = 0.60, P<0.05; delayed image, R = 0.63, P<0.05; n = 14). There was a significant
      correlation between myocardial CR and cardiac 123I BMIPP uptake (initial image, R
      = 0.77, P<0.01; delayed image, R = 0.82, P<0.001; n = 14). CONCLUSION: Our study
      suggests an association between CR depletion and impaired fatty acid metabolism
      in various forms of heart diseases.

PMID- 17453527
TI  - Patellar cartilage lesions: comparison of magnetic resonance imaging and T2
      relaxation-time mapping.
AB  - PURPOSE: To evaluate the detection and the size of focal patellar cartilage
      lesions in T2 mapping as compared to standard clinical magnetic resonance imaging
      (MRI) at 1.5T. MATERIAL AND METHODS: Fifty-five consecutive clinical patients
      referred to knee MRI were imaged both with a standard knee MRI protocol (proton
      density-weighted sagittal and axial series, T2-weighted sagittal and coronal
      series, and T1-weighted coronal series) and with an axial multislice multi-echo
      spin-echo measurement to determine the T2 relaxation time of the patellar
      cartilage. MR images and T2 maps of patellar cartilage were evaluated for focal
      lesions. The lesions were evaluated for lesion width (mm), lesion depth (1/3,
      2/3, or 3/3 of cartilage thickness), and T2 value (20-40 ms, 40-60 ms, or 60-80
      ms) based on visual evaluation. RESULTS: Altogether, 36 focal patellar cartilage
      lesions were detected from 20 human subjects (11 male, nine female, mean age 40+/
      15 years). Twenty-eight lesions were detected both on MRI and T2 maps, while
      eight lesions were only visible on T2 maps. Cartilage lesions were significantly
      wider (P = 0.001) and thicker (P<0.001) on T2 maps as compared to standard knee
      MRI. Most lesions 27 had moderately (T2 40-60 ms) increased T2 values, while two
      lesions had slightly (T2 20-40 ms) and seven lesions remarkably (T2 60-80 ms)
      increased T2 relaxation times. CONCLUSION: T2 mapping of articular cartilage is
      feasible in the clinical setting and may reveal early cartilage lesions not
      visible with standard clinical MRI.

PMID- 17453528
TI  - Multidetector computed tomography imaging of facial trauma in accidental falls
      from heights.
AB  - PURPOSE: To assess multidetector computed tomography (MDCT) findings in facial
      trauma in adults who accidentally fall from heights. MATERIAL AND METHODS: Of the
      MDCT scans of 2413 cases requested by emergency-room physicians for suspected
      facial injury, 155 (age 15.3-76.7, mean 42.0 years; 134 male, 21 female) met the
      criteria of falling from heights. These were reviewed by two researchers by
      consensus. RESULTS: Of these 155, 118 (104 male, 14 female) had 247 fractures,
      while 37 had no fracture. The fractures were classified into 13 categories, the
      zygomatic complex being the region most frequently involved. Mean falling height,
      known in 132 of 155 cases, was 5.7 m (range 0.4-25) in all, 6.0 m (0.4-25) in
      those suffering a fracture, and 5.0 m (range 0.4-13) in those without a fracture.
      Patients with Le Fort II, Le Fort III, or frontal bone fractures had fallen
      higher and frequently had associated skull base fractures, but with considerable
      overlap in falling heights. Zygomatic arch and nasal bone fractures rarely
      occurred solitarily. CONCLUSION: In a fall-from-height injury, nasal bone and
      zygomatic arch fractures indicate the presence of more severe fractures. Height
      cannot solely predict injury probability. Clear sinus sign is a valuable aid in
      assessing midface trauma in falls from heights.

PMID- 17453529
TI  - Thin-section diffusion-weighted magnetic resonance imaging of the brain with
      parallel imaging.
AB  - BACKGROUND: Thin-section diffusion-weighted imaging (DWI) is known to improve
      lesion detectability, with long imaging time as a drawback. Parallel imaging (PI)
      is a technique that takes advantage of spatial sensitivity information inherent
      in an array of multiple-receiver surface coils to partially replace time
      consuming spatial encoding and reduce imaging time. PURPOSE: To prospectively
      evaluate a 3-mm-thin-section DWI technique combined with PI by means of
      qualitative and quantitative measurements. MATERIAL AND METHODS: 30 patients
      underwent conventional echo-planar (EPI) DWI (5-mm section thickness, 1-mm
      intersection gap) without parallel imaging, and thin-section EPI-DWI with PI (3
      mm section thickness, 0-mm intersection gap) for a b value of 1000 s/mm(2), with
      an imaging time of 40 and 80 s, respectively. Signal-to-noise ratio (SNR),
      relative signal intensity (rSI), and apparent diffusion coefficient (ADC) values
      were measured over a lesion-free cerebral region on both series by two
      radiologists. A quality score was assigned for each set of images to assess the
      image quality. When a brain lesion was present, contrast-to-noise ratio (CNR) and
      corresponding ADC were also measured. Student t-tests were used for statistical
      analysis. RESULTS: Mean SNR values of the normal brain were 33.61+/-4.35 and
      32.98+/-7.19 for conventional and thin-slice DWI (P>0.05), respectively. Relative
      signal intensities were significantly higher on thin-section DWI (P<0.05). Mean
      ADCs of the brain obtained by both techniques were comparable (P>0.05). Quality
      scores and overall lesion CNR were found to be higher in thin-section DWI with
      parallel imaging. CONCLUSION: A thin-section technique combined with PI improves
      rSI, CNR, and image quality without compromising SNR and ADC measurements in an
      acceptable imaging time.

PMID- 17453530
TI  - Diffusion-weighted magnetic resonance imaging in rhombencephalitis due to
      Listeria monocytogenes.
AB  - We present diffusion-weighted imaging findings of a case of rhombencephalitis due
      to Listeria monocytogenes. It is a rare, life-threatening disorder. The diagnosis
      is difficult by clinical findings only. In this report, we aim to draw attention
      to the role of conventional and diffusion-weighted magnetic resonance imaging
      findings. To our knowledge, this is the first case report in the literature with
      apparent diffusion coefficient values of diseased brain parenchyma.

PMID- 17453531
TI  - Imaging of brown fat associated with adrenal pheochromocytoma.
AB  - The association of adrenal pheochromocytoma and brown fat has been described in
      the pathology literature and scantily in the radiology literature. We present a
      case of diffuse collection of brown fat in both perinephric spaces associated
      with left adrenal pheochromocytoma, and describe the computed tomography and
      magnetic resonance imaging findings.

PMID- 17453533
TI  - Multimarker strategy in acute coronary syndrome--pro-multimarker.

PMID- 17453534
TI  - Early pharmacological treatment of acute heart failure syndromes: a systematic
      review of clinical trials.
AB  - CONTEXT: Acute Heart Failure Syndromes (AHFS) is a common admission diagnosis
      associated with high mortality and hospital readmissions. Given the mixed results
      of recent clinical trials, the early management of AHFS remains controversial.
      OBJECTIVE: To review the recent evidence regarding current and investigational
      therapies for the early management of AHFS. DATA SOURCES: A systematic search of
      peer-reviewed publications was performed on MEDLINE and EMBASE from January 1990
      to August 2006. The results of unpublished or ongoing trials were obtained from
      presentations at national and international meetings and pharmaceutical industry
      releases. Bibliographies from these references were also reviewed, as were
      additional articles identified by content experts. STUDY SELECTION AND DATA
      EXTRACTION: Criteria used for study selection were controlled study design,
      relevance to clinicians and validity based on venue of publication and power
      analysis. DATA SYNTHESIS: Although all current intravenous therapies for the
      early management of AHFS appear to improve hemodynamics, this may not always
      translate into short-term clinical benefit. CONCLUSION: The results of the trials
      conducted to date in AHFS have generally been disappointing. There is, therefore,
      an unmet need for new therapeutic approaches for the early management of AHFS
      that may improve the short-term and long-term outcomes.

PMID- 17453535
TI  - ST elevation myocardial infarction and renal impairment. Does it matter how we
      reperfuse?
AB  - The treatment of patients with ST elevation acute myocardial infarction (STEAMI)
      and renal failure (RF) represents one of the most challenging problems with which
      the cardiologists are faced. It has been well established that patients suffering
      of acute coronary syndromes with concomitant renal failure have a worse outcome
      as compared with those with normal renal function. Leading causes for this
      adverse outcome are excess comorbidities in patients with renal failure, lesser
      use of beneficial therapies and the unique pathophysiology involved in the
      diseased kidney. The entire setup of abnormalities in coagulation, fibrinolysis,
      platelet aggregation, lipids metabolism, endothelial function and a high
      inflammatory state, is responsible for the increased risk of restenosis,
      recurrent myocardial infarction, congestive heart failure, and cardiovascular
      death among cardiac patients with impaired renal function. The results provided
      by the very small number of studies in literature evaluating methods of
      reperfusion in patients with ST elevation myocardial infarction and impaired
      renal function are very sparse, and a prospective trial to solve this therapeutic
      dilemma that clinicians are faced with, at the bedside of patients with STEAMI
      and RF is needed.

PMID- 17453536
TI  - Causes of death and re-hospitalization in cardiogenic shock.
AB  - BACKGROUND: In cardiogenic shock, causes of death usually are cardiac. However, a
      systemic inflammatory response syndrome may influence outcome. METHODS: SHould we
      emergently revascularize Occluded Coronaries in cardiogenic shocK? (SHOCK) Trial
      patients (n = 302) were analyzed regarding cause of death and re-hospitalization.
      RESULTS: Deaths (n = 180) occurred < or =30 days in 86% and >30 days in 14%.
      Known causes of death < or =30 days were cardiac in 88% (37% arrhythmic) and non
      cardiac in 12% (29% septic). Non-cardiac deaths < or =30 days occurred later (206
      [91,394] versus 41 [15,156] h, P<0.01) and were more frequently associated with
      signs of inflammation (43 versus 12%, P = 0.01) than cardiac deaths < or =30
      days. Known causes of in-hospital death >30 days (n = 19) were cardiac in 58% and
      non-cardiac in 42%. Among deaths < or =30 days systemic vascular resistance index
      was higher (2,666+/-1,063 versus 2,090+/-731 dynes.sec.cm(-5) m(2), P = 0.05)
      than among deaths >30 days. Among the 116 survivors of the initial
      hospitalization with data available, 52 (45%) were readmitted, most of which due
      to heart failure (n = 22, 42%) and myocardial ischemia (n = 16, 31%).
      CONCLUSIONS: In CS, early deaths < or =30 days are mainly cardiac. Non-cardiac
      deaths are associated with signs of inflammation. In survivors of the initial
      hospitalization, re-hospitalizations are due to heart failure and myocardial
      ischemia.

PMID- 17453537
TI  - Impact of renal dysfunction and glucometabolic status on one month mortality
      after acute myocardial infarction.
AB  - Patients with impaired glucometabolic status or renal function have a higher
      mortality after acute myocardial infarction. It is unclear whether this higher
      risk is independent or related to the quality of care. In a prospective registry,
      stress hyperglycaemia (SH) was defined as glucose level>140 mg/dl. Renal function
      was assessed by the glomerular filtration rate (GFR): normal (>/=60), mild (30
      60) and severe dysfunction (<30 ml/min/1.72 m(2)). The level of risk was assessed
      by the TIMI risk index and the quality of care by the rate of use of five
      guidelines-recommended treatments. Among the 1388 patients included, 23% had
      diabetes, 16% had SH, renal function was normal in 55%, mildly impaired in 35%
      and severely impaired in 9.5%. At one month, the mortality rate was higher in
      patients with SH (18%) as compared with diabetics (9%) or those with normal
      glucometabolic status (5%). Similarly, the mortality rate was higher in those
      with impaired renal function. Multivariable analysis identified SH, GFR group,
      TIMI risk index, ST segment elevation MI and quality of care as independent
      predictors of one-month mortality. In patients with acute MI, SH and GFR<30
      ml/min/m(2) are independent predictors of mortality after adjustment for the
      level of risk and acute care.

PMID- 17453538
TI  - Gender differences in mortality after acute myocardial infarction with mild to
      moderate heart failure.
AB  - BACKGROUND: Heart failure (HF) is associated with poor outcome after acute
      myocardial infarction (AMI). Women have higher mortality rate than men after AMI,
      however, it is unknown whether women with HF after AMI have different prognosis
      than men. AIM: To compare the prognosis of men and women with AMI and mild
      moderate HF. METHODS: We analyzed data of 3456 consecutive patients with AMI
      hospitalized in all cardiac care units in Israel during two nationwide surveys.
      RESULTS: Among patients with AMI and HF on admission: women were older, had more
      risk factors, and were less likely to undergo percutaneous coronary
      angiography/intervention. Women with HF had higher (7-days, 30-days, and 1-year)
      crude mortality rates than men. However, adjusted mortality rates were not
      significantly different between genders. CONCLUSIONS: Women with AMI complicated
      by HF had higher crude mortality rate than men that was eliminated after
      multivariate analysis, suggesting that the higher mortality rate may be
      attributed to increased prevalence of risk factors and lower rate of
      revascularization and medical therapies among women. Women with AMI and HF should
      be considered as a high-risk subgroup with adverse outcome. It remains to be
      determined whether more intensive management will improve their prognosis.

PMID- 17453539
TI  - Differences in plaque composition and distribution in stable coronary artery
      disease versus acute coronary syndromes; non-invasive evaluation with multi-slice
      computed tomography.
AB  - BACKGROUND: Plaque composition rather than degree of luminal narrowing may be
      predictive of acute coronary syndromes (ACS). The purpose of the study was to
      compare plaque composition and distribution with multi-slice computed tomography
      (MSCT) between patients presenting with either stable coronary artery disease
      (CAD) or ACS. METHODS: MSCT was performed in 22 and 24 patients presenting with
      ACS or stable CAD, respectively. Coronary lesions were classified as calcified,
      non-calcified or mixed while signal intensity (SI) was measured. RESULTS: In
      patients with stable CAD, the majority of lesions were calcified (89%). In
      patients with ACS, less calcifications were observed with a greater proportion of
      non-calcified (18%) or mixed (36%) lesions (P<0.001). Accordingly, mean SI of
      plaques was significantly less in ACS (320+/-201 HU versus 620+/-256 HU in stable
      CAD, P<0.001). Dividing lesions in the ACS group according to culprit versus non
      culprit vessel location resulted in no significant difference in average SI
      between these two groups while still lower as compared to stable CAD (P<0.001).
      CONCLUSIONS: In patients with ACS, significantly less calcifications were present
      as compared to stable CAD. Moreover, even in non-culprit vessels, multiple non
      calcified plaques were detected, indicating diffuse rather than focal
      atherosclerosis in ACS.

PMID- 17453540
TI  - Initial experience with the Amplatzer membranous septal occluder in adults.
AB  - OBJECTIVES: Most perimembranous ventricular septal defects (pmVSD) that are still
      patent in adult life are small, hemodynamically and clinically unimportant, and
      do not require any intervention. However, surgery in adulthood for those that
      need to be closed carries significant morbidity. A trans-catheter technique for
      closing pmVSDs has been developed, and this paper describes our initial
      experience using the Amplatzer membranous septal occluder (AMSO).
      PATIENTS/METHODS: Twelve patients, 9 female and 3 male, median age 34.5 years
      (range: 21-67) underwent catheterization for attempted pmVSD closure. Ten of the
      defects were native and 2 were post-operative residual defects. Transcatheter VSD
      closure was performed as previously described, under general anesthesia and with
      trans-esophageal echocardiographic (TEE) monitoring. Patients had a moderate to
      large left to right shunt (mean Qp/Qs = 2.0+/-0.4) with mild left heart volume
      overload and near normal pulmonary pressure. All 10 native pmVSDs were closed
      successfully, 9 with AMSO and one with an Amplatzer muscular VSD occluder, after
      failure to implant the AMSO. There was one post procedural complication--self
      limiting retroperitoneal bleeding. Three patients had a residual leak. Attempted
      VSD closure in the 2 patients with post surgery residual shunt was unsuccessful.
      CONCLUSION: We conclude that transcatheter mVSD closure with the AMSO is an
      efficient and safe alternative to surgery in carefully selected adult patients
      with native pmVSDs.

PMID- 17453541
TI  - Device closure of membranous ventricular septal defects in adults: an alternative
      to surgical closure.

PMID- 17453542
TI  - An abnormal finding in an angiogram.
AB  - An 80 year old Chinese gentleman was admitted with NSTEACS characterized by
      anterior T wave inversion and raised Troponin T. His coronary angiogram showed
      stenosis of the proximal LAD. He underwent PCI to LAD lesion. The RCA was large
      and there was large collateral between, RCA and PA (fig 1,2), which was not
      intervened. He made good recovery and has been asymptomatic for over 2 years.
      Coronary artery anomalies are found in 1% of the population, RCA is the most
      commonly involved. Best approach would be to observe the patients, as most of
      them do not develop any symptoms.

PMID- 17453543
TI  - Hemodilution during cardiopulmonary bypass: optimal hematocrit for safe outcome.
AB  - Studies have implicated hemodilution during cardiopulmonary bypass (CPB) as an
      independent risk factor for perioperative morbidity and mortality, however, it is
      plausible that the variability in results so far quoted are species-specific or
      blood product covariate dependent. Nevertheless, obvious debate regarding the
      optimal degree of hemodilution during CPB with regard to patients' outcome still
      prevails in the modern cardiac surgery era. We agree from the reported arguments
      that the range of absolute differences in the perioperative hematocrit (HCT) seem
      more reasonable to use than individual values yet we present a new avatar of
      evidence in this letter regarding the optimal HCT to be used during
      normo/hypothermic CPB.

PMID- 17453544
TI  - Insight in coping with dementia: listening to the voice of those who suffer from
      it.

PMID- 17453545
TI  - Living with dementia from the perspective of older people: is it a positive
      story?
AB  - Dementia, even at an early stage, may pose problems and challenge one's quality
      of life. Having accurate knowledge of what one experiences when living with
      dementia is important for developing proactive care for individuals with dementia
      and their families. The aim of our Grounded Theory study was to explore what it
      means for elderly people to live with early-stage dementia. We interviewed 20
      elderly people with probable mild dementia and their family members. Living with
      dementia was often presented as a positive narrative, one that told of only minor
      problems and which stressed abilities and contentment with life. Being valued,
      rather than losing one's cognition or identity was central in their experience.
      More in-depth analyses of participants' narratives revealed, however, that they
      were constantly balancing their feelings of value and worthlessness, struggling
      to remain someone of value. This struggle was prompted by threats posed by
      dementia and by the persons' interactions with others. Superficially, a positive
      narrative may be understood as a lack of awareness or as denial due to cognitive
      loss. Our findings suggest, however, that we should look beyond this superficial
      view and seek to understand the narrative as an expression of one's attempt to
      counterbalance devaluation.

PMID- 17453546
TI  - Investigating the ways that older people cope with dementia: a qualitative study.
AB  - Understanding the way that older people cope with dementia has important
      implications for the enhancement of the psychological well-being and quality of
      life of this group of people. This qualitative study explored how older people
      cope with dementia, by engaging 12 people with early-stage dementia in semi
      structured interviews. Interpretative phenomenological analysis (IPA) was used to
      identify the shared themes in participants' accounts. Three major themes emerged:
      "managing identity in relation to dementia", "making sense of dementia", and
      "coping strategies and mechanisms" (the latter theme divided into "everyday,
      individual strategies", "coping in relation to others", and "personal
      attitude/approach"). There were also two additional themes in relation to process
      issues: issues of "conflict and control" which were evident across all other
      themes, as was individuality and the importance of "context" in coping with
      dementia. These findings are discussed in the relation to previous research in
      this field, and suggestions for further research and clinical practice are
      outlined.

PMID- 17453547
TI  - The use of everyday technology by people with dementia living alone: mapping out
      the difficulties.
AB  - While the technological development available to society is taking quantum leaps,
      we have little knowledge of how people with mild dementia manage to cope with
      familiar technology at home, such as television and electronic household
      machines, or new technology, such as remote controls, cell phones and computers.
      As this technology represents a potential problem area, the aim of this
      qualitative, exploratory study was to identify and characterize difficulties with
      and hindrances to using everyday technology, as they appeared in data, for
      persons with early stage dementia. Eight participants with dementia were included
      in an extensive data collection consisting of repeated interviews and
      observations made in the home; the data were analyzed adopting a constant
      comparative approach. The results exhibit a taxonomy of difficulties in four
      domains, encompassing conditions that interfere with the use of the technology,
      deficiencies in knowledge and in the communication between users and their
      technology, and limitations in the use of instructions. Typically, difficulties
      appeared in complex combinations. They arose when familiar technology was being
      used, and not only when new technology was to be used. This raised concerns about
      the need these people have for support in home and in society. Further research
      is needed to validate the findings.

PMID- 17453548
TI  - The long-term effects of war experience.

PMID- 17453549
TI  - The impact of resource loss on Holocaust survivors facing war and terrorism in
      Israel.
AB  - We examined the distress level of 102 Holocaust survivors in Israel during a
      recent period of continuous exposure of the Israeli population to terror and the
      threat of missile attack. Based on the Conservation of Resources (COR) theory, we
      explored the contribution of losses suffered during the Holocaust and of current
      loss of resources due to terror attacks on their distress level. Twenty one
      percent of the sample had probable PTSD and high psychological distress levels in
      general. Current loss of psychosocial resources contributed significantly to
      survivors' current PTSD symptomatology and general psychological distress, above
      the contribution of the previous Holocaust-related loss. Our findings support COR
      theory, which states that traumatic events are associated with ongoing and often
      rapid loss of resources. Resource loss, in turn, is associated with higher
      distress levels. Moreover, current loss of resources compounds the impact of
      earlier resource losses incurred during the Holocaust.

PMID- 17453550
TI  - The long-term impact of war experiences and evacuation on people who were
      children during World War Two.
AB  - During World War Two 1.9 million people were evacuated from British cities where
      the risk of bombing was perceived to be highest. 1.5 million of these were
      children who, often unaccompanied, were sent to live with strangers. Two hundred
      and forty-five people who were evacuated as children were compared with 96 of
      similar age who did not experience evacuation. Within this self-selected sample,
      significant numbers of the evacuees were found to have experienced abuse and
      neglect. Pre-evacuation abuse made continued abuse likely during evacuation,
      while abuse during evacuation led to children being more likely to continue to be
      abused on their return home. Abuse during evacuation led to increased scores on
      the Impact of Event Scale and General Health Questionnaire, and to insecure
      attachment patterns. The role of evacuation and abuse in the maintenance of long
      term psychological problems is discussed.

PMID- 17453551
TI  - Assessing late-onset stress symptomatology among aging male combat veterans.
AB  - This study's goal was to develop a measure of late-onset stress symptomatology
      (LOSS). LOSS is a phenomenon observed in aging combat veterans who (a) were
      exposed to highly stressful combat events in their early adult years, (b) have
      functioned successfully throughout midlife with no history of chronic stress
      related disorders, but (c) begin to register increased combat-related thoughts,
      feelings, and reminiscences commensurate with the changes and challenges of
      aging. Several samples of older male combat veterans from World War II, the
      Korean Conflict, and the Vietnam War served as participants. We developed a LOSS
      Scale that demonstrated a high degree of internal consistency reliability
      (coefficient alpha = 0.97). Scores were stable over brief intervals but were
      sensitive to developmental change over an extended period. Factor analysis
      suggested a single LOSS factor. Bivariate associations between LOSS score and
      other variables (e.g., indicators of contemporary life stressors, resilience,
      quality of life) were consistent with hypotheses, and there was support for the
      incremental validity of LOSS vis-a-vis posttraumatic stress symptoms and symptoms
      of general distress. Discussion of the potential uses of the scale, future
      directions for psychometric research, and suggestions for generalizing the LOSS
      construct to other trauma populations are provided.

PMID- 17453552
TI  - The after-death call to family members: a clinical perspective.
AB  - In this paper, we discuss the value of an after-death telephone call made by the
      treating mental health clinician to family members, after the death of a
      geriatric patient with a psychiatric disorder. We outline the process of the
      after-death call including the optimal method, nature, and content. We note the
      psychotherapeutic value of an after-death telephone call in addressing complex
      emotions, and helping the family to cope with bereavement. We also discuss
      institutional, legal, and ethical ramifications. We conclude that an after-death
      call may be of sufficient benefit to be considered as a "best practice" approach
      in the care of every patient.

PMID- 17453553
TI  - Physician attitudes toward treatment of depression in older medical inpatients.
AB  - OBJECTIVES: To better understand low treatment (<50%) and psychiatry referral
      rates (<10%) of depressed older medical patients, we examined medical physicians'
      characteristics, attitudes and practices regarding treatment. METHODS: Physicians
      caring for a consecutive series of 1000 depressed older patients during medical
      hospitalization and/or after discharge were asked about their general attitudes
      and behaviors related to the treatment of depression in older patients. RESULTS:
      Of 422 physicians responding to questionnaires, less than half (48%) usually
      started more than two patients a month on antidepressants. Even fewer (14%)
      referred more than two patients a month for counseling; 37% usually referred
      none. Only 11% referred more than two patients a month to psychiatrists; nearly
      40% usually referred none. Antidepressants, counseling, and psychiatric referral
      were seldom thought very effective. Physicians out of their training and those in
      primary care specialties (especially family practice) were more likely to treat
      patients. Common reasons for not treating these patients were perceived
      resistance to treatment (62.3%), lack of time (61.1%), uncertainty of depression
      diagnosis (56.2%), belief that patients couldn't afford treatment (50.5%), and
      concern about medication/disease interactions (58.8%). One-third (33.5%)
      emphasized that they were unsure about treatment effectiveness and one-third
      (34.4%) that they were poorly prepared to treat depression in older patients. Non
      white physicians were more likely to refer to psychiatrists. CONCLUSIONS: Many
      older depressed patients in medical settings are not treated or referred.
      Physician experience and specialty may affect the decision to treat, and
      physician race may affect the decision to seek consultation. Therapeutic nihilism
      may be influential.

PMID- 17453554
TI  - Social support and adjustment to caring for elder family members: A multi-study
      analysis.
AB  - This multi-study analysis systematically examines research findings on
      relationships between social support and caregiver adjustment to discover whether
      informal support helps family caregivers. Caring for older relatives is an
      ongoing stressful life course event and role. Informal social support is often
      used as a predictor of caregiver adjustment outcomes. It is widely believed to
      enhance adjustment. Yet the varied research results do not necessarily support
      this belief. A computer-generated literature search of social sciences and
      medical databases produced thirty-five caregiving articles, published in refereed
      journals, which meet study parameters. A coding form was developed to categorize
      social support and adjustment variables for cross-tabular analyses. The findings
      show most relationships (61%) between social support and caregiver adjustment are
      not positively significant. Of the minority of positively significant
      relationships, neither perceived (available) nor received support is more
      important and neither instrumental nor socioemotional support is more likely to
      aid adjustment. Researchers and health care professionals need to explore the
      negative impact of social support and attributes of caregiver-care recipient
      relationships.

PMID- 17453555
TI  - Carers Assessment of Difficulties Index (CADI): psychometric properties for use
      with carers of people with dementia.
AB  - Burden is a commonly recognised phenomenon in family caring. The Carers
      Assessment of Difficulties Index (CADI) was developed as a clinical tool for
      assessing the multiple dimensions of carer burden. It has been used with a number
      of caring cohorts, but its psychometric properties have not been explored
      specifically with carers of people with dementia. The 30-item CADI was
      administered to 232 carers of people with dementia with the aim of assessing the
      suitability of the frequency scale for clinical and research use with this
      population. The psychometric properties were examined, including descriptive
      data, a principal components analysis (PCA), and a reliability analysis on the
      resultant components. All items were experienced by some participants, but no
      item was experienced by all. An 8- factor solution from the PCA explained 59% of
      the variance. Eight subscales were established with good internal consistency. It
      is concluded that the CADI is suitable for both clinical and research use with
      carers of people with dementia.

PMID- 17453556
TI  - Health service use and outcome: comparison of low charge, integrated,
      comprehensive services with usual health care.
AB  - We examined the effects of use of low charge, integrated and comprehensive health
      care services (Veterans Administration (VA) health care system) on health care
      service use and health-related outcomes. Data came from the 10-year (1986/87
      1996/97) Duke Established Populations for Epidemiologic Studies of the Elderly,
      with 159 men aged 65-85 who primarily used VA health services compared with 1,100
      men aged 65-85 who did not. In controlled analyses, no differences were found
      between the two groups on number of OTC medications used, or in speed or
      likelihood of entering a nursing home. However, veterans who primarily used the
      VA health care system reported more outpatient visits and prescription drugs, and
      increased likelihood of using an adjunct health care provider; entry into a
      hospital was quicker, and number of hospitalizations was greater. Although health
      status was controlled, because of eligibility requirements it remains possible
      that veterans were sicker. Nevertheless, no differences were found in health
      outcome (functional status or mortality). Readier access to better integrated
      health services appears to result in increased use of health services controlled
      by the health care provider, but not of services requiring the recipient's
      relocation, while functional status and mortality attained equivalence.

PMID- 17453557
TI  - Progressive age-related changes in the attentional blink paradigm.
AB  - Previous studies on aging and attention typically examine group differences
      between younger and older adults, rather than seeing aging as a continuous
      process. Using correlational analyses, this study examined progressive changes in
      the magnitude of the attentional blink (AB) associated with aging. Increased age
      was found to be significantly associated with the ability to detect the second
      target (T2), whereby older age was correlated with the production of a longer and
      more pronounced AB; this supports the proposition that aging is associated with
      reduced inhibitory processes and selective attention. It was also found that AB
      performance somewhat improves between ages 18-39 years, but tends to decline from
      40 years of age onward, providing an interesting and novel finding that AB
      effects may become more sensitive at this point in time. The AB task may prove
      useful in the assessment of selective attention in normal healthy adults, as well
      as changes associated with pathological aging.

PMID- 17453558
TI  - Alzheimer's disease patients' cognitive status and course years prior to symptom
      recognition.
AB  - This is a prospective examination of the cognitive performance and cognitive
      course of persons in an asymptomatic "preclinical" phase who eventually developed
      Alzheimer's disease (AD). We compared performances on the Mayo Cognitive Factor
      Scales (MCFS) of 20 persons in a neurologically normal cohort who subsequently
      developed AD to the performances of 60 persons who remained free of dementia
      symptoms. For the AD patients, exams occurred prior to the appearance of dementia
      symptoms (an average of 4.2 and 1.5 years prior to symptom onset). Results reveal
      strong group differences on learning and retention, with eventual AD patients
      scoring lower than controls years prior to reporting symptoms of the disease.
      There was no significant interaction effect (group x testing session) for memory
      retention, suggesting that memory decline in this preclinical period may be too
      slow to be a useful indicator of future AD. A significant interaction (but no
      group effect) was seen for verbal comprehension.

PMID- 17453559
TI  - Age-related effects in prospective memory are modulated by ongoing task
      complexity and relation to target cue.
AB  - Two experiments examined the puzzling variation in the age-related patterns for
      event-based prospective memory tasks. Both experiments involved a famous faces
      ongoing task with a feature of the famous face as the target for the prospective
      memory task. In Experiment 1, a substantial age deficit was found on the
      prospective memory task when the cue was nonfocal (wearing glasses) to the
      ongoing task, replicating previous research, but this deficit was significantly
      reduced with a focal cue (first name John). In Experiment 2, the prospective
      memory cue (wearing glasses) was held constant and the demands of the ongoing
      task of naming faces were varied. The substantial age differences found with a
      nonfocal cue were eliminated when the ongoing task was made less challenging. The
      findings help reconcile the divergent age-related findings reported in the
      literature.

PMID- 17453560
TI  - Cognitive and non-cognitive factors contributing to the longitudinal
      identification of successful older adults in the betula study.
AB  - Studies of successful aging have typically defined elderly who fall in the upper
      end of a distribution of test scores as successful. A different definition of
      successful aging requires that older adults fall at or above the mean level of
      younger adults and maintain this level over time. Here we examined this
      definition of successful aging in a sample of 1463 individuals between the ages
      of 50 of 85. Based on principal coordinate analysis of cognitive and non
      cognitive variables, we identified a group of 55 (8.3%) 70-85 years olds that
      were high functioning. This group of elderly showed elevated performance on a
      range of cognitive tasks. Non-cognitive factors that characterized this group
      included education and subjective health. The participants were retested 5 years
      later and the same type of analysis was repeated. Of the remaining individuals
      who initially were classified as high functioning, 18 (35%) remained high
      functioning and thus met the definition for successful aging. Years of education
      was a significant predictor of who remained successful over time.

PMID- 17453561
TI  - Effects of age and divided attention on memory components derived for the
      category exemplar generation task.
AB  - Age differences in memory performances on a conceptually driven task, the
      category exemplar generation (CEG) test, were investigated. Thirty-six younger
      adults and 36 healthy older adults studied word lists in full and divided
      attention conditions. Recall was tested with category names. The process
      dissociation procedure was used to derive estimates of controlled and automatic
      memory. Old-old adults (70-84 years) exhibited poorer conscious recollection than
      both younger (18-24) and young-old adults (59-69). In contrast, no age
      differences were found in estimates of automatic memory. For the younger and
      older adults, the divided encoding manipulation reduced both the consciously
      controlled and automatic estimates of memory. The results suggest that the few
      prior findings of age deficits in priming on the CEG may have been an artifact of
      contamination from conscious retrieval processes. They also indicate that the
      opportunity for greater semantic processing enhances the conceptual priming of
      both younger and older adults.

PMID- 17453562
TI  - Effects of hormone replacement therapy and aging on cognition: evidence for
      executive dysfunction.
AB  - The present study was designed to explore whether the frontal lobe hypothesis of
      cognitive aging may be extended to describe the cognitive effects associated with
      estrogen use in postmenopausal women. Postmenopausal estrogen-only users,
      estrogen + progesterone users, and non-users (60-80 years old), as well as young,
      regularly cycling women (18-30 years old) completed an item and source memory
      task. Since source memory is thought to rely more on executive processes than
      item memory, we hypothesized that aging and estrogen effects would be greater for
      source memory than for item memory. Neuropsychological tests explored whether the
      effects of aging and estrogen use were revealed on other tests of frontal lobe
      function. Results from the experimental task revealed greater aging and estrogen
      effects for source memory than for item memory, and neuropsychological results
      revealed aging and estrogen effects on a subset of tests of executive function.
      Women on estrogen + progesterone therapy did not outperform non-users, suggesting
      that the addition of progesterone to hormone therapy may mitigate the benefits
      induced by estrogen use alone. Overall, findings support the hypothesis that
      estrogen use may temper age-related cognitive decline by helping to maintain
      functions subserved by the frontal lobes.

PMID- 17453563
TI  - Family, cultural and gender role aspects in the context of HIV risk among African
      American women of unidentified HIV status: an exploratory qualitative study.
AB  - This was an exploratory, qualitative study of contextual cultural and social
      realities of the sexual interactions of a representative sample of African
      American women of unidentified HIV status. The study expanded our understanding
      of family and gender role variables by exploring influences of family of origin
      and idealistic perceptions of roles on sexual relationships. Data was collected
      on 51 African American women who were recruited through probability sampling.
      Between 39% and 70% of study participants reported at least one of the following
      HIV risk factors: low condom use, substance use during sex, partner's
      incarceration and history of abuse. Nonetheless, all women in our study perceived
      their chances of HIV infection to be almost non-existent, despite a fairly good
      knowledge of HIV/AIDS modes of transmission including that anyone could become
      HIV infected, knowing somebody with HIV/AIDS and acknowledgment, among some, of
      their partner's infidelity and risk behaviors. Our analysis revealed that
      parental communications about sexuality in relationships focused largely on trust
      (being mistrustful of men) and women's control of their sexual impulses. Trust
      was also emphasized (desired) by women in the discussions of gender roles. Women
      reported a strong reliance on God and made frequent references to the role of the
      church in HIV prevention. Our findings offer suggestions for HIV prevention for
      the general population of African American women. HIV-prevention messages that
      consider their views of relationships, gender roles, sexual abuse history and the
      role of the church are suggested.

PMID- 17453564
TI  - Risk and protective factors for psychological well-being of children orphaned by
      AIDS in Cape Town: a qualitative study of children and caregivers' perspectives.
AB  - By 2020, an estimated 2.3 million South African children will be orphaned by
      HIV/AIDS (Actuarial Society of South Africa, 2005), but little is known about
      risk and protective factors for their emotional and behavioural well-being. This
      qualitative study explores perspectives of affected families. Orphaned children
      (n = 60), caregivers of orphaned children (n = 42) and social care professionals
      (n = 20) completed semi-structured interviews and focus groups. Participants were
      recruited from schools, shelters and welfare services. Findings from multiple
      sources indicate potential risk and protective factors in a range of dimensions,
      including bereavement, family functioning, social support, poverty, access to
      education and perceived stigma. Many factors reflected international literature
      on children experiencing similar stressors (e.g. non HIV/AIDS-related
      bereavement). However, this study also identified factors which may be specific
      to this group, notably stigma, abuse and peer factors. Current research is
      quantitatively testing associations between these identified factors and
      psychological outcomes.

PMID- 17453565
TI  - Africa's orphan crisis: two community-based models of care.
AB  - The AIDS epidemic has created a crisis for children, severely threatening the
      health and development of children whose parents are ill, have died and whose
      communities have lost a large percentage of their adults. Even when extended
      family can serve as guardians, their need to work in the context of widespread
      poverty decreases the amount of time they are able to spend with children. Other
      children live in child-headed households or with seniors unable to provide
      adequate care. Relative to the size of the need there are few interventions that
      provide support to orphans in sub-Saharan Africa. We report on two different
      models of community-based care that have emerged to fill this caregiving gap, and
      highlight the relative advantages of each. These programmes, one centralized and
      the other decentralized, are an effective means of caring for orphans and could
      be scaled up in other communities to meet the magnitude of the crisis.

PMID- 17453566
TI  - HIV infection in hospitalized children with endemic diseases in Abakaliki,
      Nigeria: the role of clinically directed selective screening in diagnosis.
AB  - The increasing prevalence of HIV infection in Nigeria, its similar manifestations
      with endemic diseases and limited facilities for screening calls for judicious
      HIV testing. Children aged one month to 15 years admitted into the paediatric
      ward of the Ebonyi State University Teaching Hospital between January 2000 and
      September 2001 for various endemic diseases were reviewed retrospectively. Eight
      clinical risk factors commonly associated with HIV infection and endemic diseases
      present either singly or in combination, were reviewed to determine whether they
      could help to predict HIV infection and at what level and finally help formulate
      criteria for selective screening of HIV infection. Children above 18 months of
      age were diagnosed as being infected with HIV if they tested positive by two
      different HIV enzyme-linked immunosorbent assay (ELISA) tests. In children less
      than 18 months of age the diagnosis of HIV infection was made if they were ELISA
      positive and also fulfilled the WHO criteria for symptomatic HIV infection. Of
      the 282 children reviewed 31 (11.0%) were HIV positive giving a sero-prevalence
      rate of 4.1% of total admission. The HIV seropositive rate was highest in oral
      candidiasis (OC) (38.2%), followed by severe malnutrition (SM) (33.8%) then
      generalized lymphadenopathy (GLN) (31.4%). The presence of SM, GLN, OC and
      chronic dermatitis were highly significant independent risk factors for
      predicting HIV seropositivity (p<0.05). A marked shift towards the likelihood of
      HIV sero-positivity in the presence of at least two of the eight risk factors was
      documented. Children with two risk factors present had a 9.1 times more risk of
      being HIV sero-positive compared with those who had only one risk factor present
      (chi(2)=11.6, p=0.0007, OR = 9.1, 95% Cl = 2.5-32.8). Thirteen children (41.9%)
      representing a vast majority of HIV-positive children showed evidence of at least
      two of the eight clinical risk factors. As the number of risk factors
      concomitantly present increased, the chances of the child being infected with HIV
      also increase significantly (p<0.0001). Our study shows that clinically-directed
      selective screening in the presence of at least two risk factors should be
      carried out which does have a practical role in early diagnosis of HIV infection
      in a resource-poor setting.

PMID- 17453567
TI  - Extended family caring for children orphaned by AIDS: balancing essential work
      and caregiving in a high HIV prevalence nations.
AB  - While over 90 per cent of the 15 million children who have been orphaned by
      HIV/AIDS are cared for by family members, there is little information about
      whether adults can meet orphans' essential caregiving needs while working to
      economically survive. Using a survey we conducted in Botswana of 1033 working
      adults, we analyse the experience of adults who are caring for orphans. Over one
      third of working adults were caring for orphans and many with few financial
      resources: 82% were living on household incomes below US$10 purchasing power
      parity adjusted per person per day. Because of their caregiving responsibilities,
      they were less able to supplement income with overtime, weekend, evening, or
      night work. At the same time caregiving responsibilities meant orphan caregivers
      spent fewer hours caring for their own children and other family members. Nearly
      half of orphan caregivers had difficulties meeting their children's needs, and
      nearly 75% weren't able to meet with children's teachers. Pay loss at work
      compounded the problems: One-quarter of orphan caregivers reported having to take
      unpaid leave to meet sick childcare needs and nearly half reported being absent
      from work for children's routine health care. This paper makes clear that if
      families are to provide adequate care for orphans while economically surviving
      there needs to be increases in social supports and improvements in working
      conditions.

PMID- 17453568
TI  - Factors related to medical appointment attendance after childbirth among HIV
      infected women in the Paris region.
AB  - This study examined factors related to medical appointment attendance after
      childbirth among HIV-infected women in the Paris region. We hypothesized that
      despite regular utilization of prenatal care, many women may not attend medical
      appointments after delivery for their own HIV infection. This was an
      observational cohort study of HIV-seropositive women delivering in four Paris
      hospitals in 2001. Follow-up attendance through 24 months after delivery was
      defined as 'regular' for women who had > or =4 HIV visits during the period,
      'irregular' for <4 visits in the 24-months period and/or a gap between two visits
      >12 months, and 'no attendance' when < or =1 visit in the 2-year period. Of 169
      women enrolled, 125 (75%) had regular attendance, 24 (14%) had irregular
      attendance, and 18 (11%) had no attendance. Multivariate analysis found the
      greater number of HIV visits during pregnancy and the prescription of combination
      therapy (versus zidovudine monotherapy) during pregnancy to be significantly
      related to regular attendance. Of the 18 women who had no attendance, 8 women
      (47%) continued to attend regular paediatric appointments with their infants
      during the 24-month period. Scheduling more frequent HIV visits during pregnancy
      may establish a pattern that will improve attendance during the post-partum
      period. In addition, increased communication between the health care providers of
      the mother and child may increase appointment attendance following delivery.

PMID- 17453569
TI  - Barriers to participation in the prevention of mother-to-child HIV transmission
      program in Gaborone, Botswana a qualitative approach.
AB  - The existing belief that if money and free antiretroviral drugs were offered to
      developing countries, people would flock to use the services does seem to hold
      for the Prevention of Mother-to-Child Transmission of HIV Program (PMTCT) in
      Botswana. The government offers free counseling, testing, free antiretroviral
      drugs and free infant formula for babies born to infected mothers and yet some
      women are reluctant to enroll in this program to protect their infants. A
      qualitative study on factors that motivated and hindered pregnant women from
      participating in the PMTCT program was conducted in Gaborone, Botswana. Forty
      subjects (ten HIV-positive pregnant women who accepted the program, eleven who
      rejected the program, nine PMTCT health workers and ten key informants)
      participated in in-depth interviews. Thematic content analysis yielded the
      following barriers to participation in the program: fear of knowing one's own HIV
      status, infant feeding distribution stigma, lack of male partners' support and
      negative attitudes of health workers. Reinforcing factors were: availability of
      free antiretroviral drugs and free infant formula. In conclusion, stigma and
      discrimination are still the main impediments to women's participation in the
      PMTCT program. Mitigating these barriers could reduce AIDS-related infant
      mortality in this country.

PMID- 17453570
TI  - Constraints to educational opportunities of orphans: a community-based study from
      northern Uganda.
AB  - The objective of this article is to assess constraints on educational
      opportunities of orphans cared for within the extended family system in Lira
      district, northern Uganda. The data were collected through: review of school
      census records; ethnographic fieldwork; in-depth interviews with 21 community
      leaders, 45 heads of households caring for orphans and 35 orphans. Focus group
      discussions were held with men and women caring for orphans, community leaders
      and orphans. A household survey was conducted in 402 households caring for
      orphans. We found that very poor widows living on less than half a dollar per day
      head 48% of the households caring for orphans. The elderly heads of households
      were 3 times more likely to have all the children in their household in schools
      than the younger ones. Furthermore, the widowed and single heads of households
      were more likely to have all orphans in school than the married, and households
      that received external support offered better educational opportunities. Poverty,
      as indicated by lack of food while at school and heavy involvement of orphans in
      domestic labour, were identified as major constraints on orphans' schooling.
      There is an urgent need to support orphans' education in northern Uganda beyond
      the current Universal Primary Education efforts. The most vulnerable households
      need to be targeted, and the communities need to be sensitized to child labour,
      school meals and sex abuse.

PMID- 17453571
TI  - Property grabbing and will writing in Lusaka, Zambia: an examination of wills of
      HIV-infected cohabiting couples.
AB  - High rates of HIV and poverty place women in a precarious economic situation in
      Lusaka, Zambia. Mortality from HIV infection is high, leaving many households
      single headed and creating almost a half a million orphans. One of the most
      prevalent forms of gender violence that creates poverty in women is when the
      male's family claims the property of the deceased from the widow and the
      children. The Zambia-Emory HIV Research Project collected 184 wills from
      individuals in monogamous unions where one or both of the individuals were HIV
      positive. Despite the fact that many wills specifically stated that their
      extended family was not allowed to tamper with their possessions in the event of
      death, property grabbing proved to be a prevalent and difficult issue in Lusaka.
      In order to improve the lives of widowed women in Lusaka, the government and
      other civic and non-governmental organisations must inform women of their rights
      to own and protect their land and other assets in the event of their husbands'
      death, an issue of increasing importance in the area of HIV/AIDS.

PMID- 17453572
TI  - HIV testing in a national sample of pregnant US women: who is not getting tested?
AB  - It is recommended that all pregnant women in the US receive an HIV test as early
      as possible during prenatal care to allow HIV-infected women to begin receiving
      anti-retroviral drugs when they most effectively prevent transmission. We
      analyzed interview data from a nationally-representative sample of pregnant women
      to examine the extent of HIV testing among pregnant women and the characteristics
      associated with testing, including access to healthcare. We used data from the
      combined 2001 and 2002 Behavioral Risk Factor Surveillance System, a nationally
      representative telephone-based behavioral survey of adults, aggregated across all
      states to yield national estimates. Among 4,855 women pregnant at interview we
      looked at the percentages recently tested and never tested by major populations
      subgroups and assessed differences using chi-square tests and multiple logistic
      regression analysis. Pregnant women were tested at a much higher rate than other
      women of the same age - 54.1% had been tested in the past year compared with
      15.4% of non-pregnant women. Categories of pregnant women that were more likely
      to never have been tested for HIV include those without a health plan or
      insurance (adjusted odds ratio (AOR): 1.6) and those without a personal doctor
      (AOR: 1.7). Women with knowledge of methods to prevent perinatal HIV transmission
      were less likely to have never been tested (AOR: 0.8). Attaining the recommended
      goal of universal prenatal testing will require attention to women without
      personal doctors or health insurance.

PMID- 17453573
TI  - Influence of the involvement of partners in the mother class with voluntary
      confidential counselling and testing acceptance for prevention of mother to child
      transmission of HIV programme (PMTCT programme) in Cambodia.
AB  - The National Maternal and Child Health Center in Phnom Penh, Cambodia commenced
      PMTCT services as the first site of the National PMTCT programme of Cambodia in
      November 2001. However, the acceptance of voluntary confidential counselling and
      testing (VCCT) in the PMTCT services was not as high as expected. The aim of this
      study was to evaluate influence of partner participation in the mother class to
      the PMTCT services. During the first visit to antenatal care, all women were
      invited to the class, where information on PMTCT was provided. From July 2002,
      when partner participation started, to May 2005, the acceptance rate to the pre
      test counselling of those who attended the class alone was 18.7% (3,234/17,340),
      while that of the attendees with their partner was 85.1% (2,908/3,417) (p
      <0.001). All of the couples accepted couple counselling and disclosure of their
      results to their partners. In conclusion, a strong association was observed
      between acceptance and partner involvement. However, we should consider also
      other strategies for future programme improvement.

PMID- 17453574
TI  - Disclosure of HIV among black African men and women attending a London HIV
      clinic.
AB  - Little research has focused specifically on disclosure among HIV+ Black Africans
      living in the UK; however, the available evidence suggests that this population
      may be reluctant to disclose to significant others. Forty-five HIV+ Black African
      men and women were recruited from a London HIV clinic. Semi-structured interviews
      gathered information on: disclosure, social support, mental and physical health,
      medication adherence, acculturation and the perceived prevalence of stigma. Both
      qualitative and quantitative analyses were conducted. The majority of the
      participants had disclosed to one significant other and there was an inverse
      association between perceived stigma and disclosure. Disclosure could not be
      predicted by any of the respondent characteristics identified in the study;
      rather, disclosure decisions were reasoned, interpersonal in nature and many of
      the motivations were specific to the individual. There was little evidence to
      suggest that those who disclosed to more than one other gained additional
      benefits in physical or mental well-being. Clinicians seeking to assist members
      of this population to disclose need to assess the specific reasons for and
      barriers against disclosure for that individual.

PMID- 17453575
TI  - An interventionist's guide to AIDS behavioral theories.
AB  - Although numerous individual-level AIDS behavioral theories (ABTs) exist in the
      literature, there is currently no consensus as to which theory is most precise in
      explaining or predicting HIV risk behavior. In the absence of empirical evidence
      favoring one ABT over another, how should an interventionist go about choosing a
      theory for one's particular prevention efforts? The current article provides an
      overview of and conceptually compares 13 ABTs in an attempt to provide guidance
      regarding this critical decision. A variety of criteria upon which one might
      judge ABTs are proposed and discussed, including empirical support for variables
      that make up the theory, whether or not theories are belief-based, AIDS-specific,
      message-based, intervention-based and behavior or behavioral-change focused.
      While all of the theories have strengths and weaknesses, the task for an
      interventionist is to choose the theory of best fit for one's particular
      prevention efforts. The suggestions provided in the current article may help with
      such a choice.

PMID- 17453576
TI  - Responsibility as a dimension of HIV prevention normative beliefs: measurement in
      three drug-using samples.
AB  - The concept of responsibility was derived originally from principles of morality,
      as part of a network of rights, duties and obligations. HIV risk-related studies
      have suggested that a sense of responsibility for condom use to protect a partner
      is a potentially important predictor of condom use in drug-using populations. We
      created a four-item scale measuring Self responsibility to use condoms and
      Partner's responsibility to use condoms. Data were collected from three drug
      using samples: crack smokers, HIV seropositive crack smokers in an intervention
      study in Houston, Texas, and Tanzanian heroin users in Dar es Salaam. Data
      indicated that the four responsibility items had high alpha coefficients in each
      sample, and that there were moderate to high intercorrelations between equivalent
      self and partner responsibility items. There were significant differences in
      scale scores between the crack smokers and the HIV positive crack smokers and the
      Tanzanian samples, but no significant differences between the HIV positive and
      Tanzanian samples. Comparing within the first crack-smoker sample those who were
      HIV positive and negative showed significant differences in the direction of
      higher beliefs in responsibility to use condoms in the HIV positive group. These
      data suggest that responsibility is measurable, holds similar psychometric
      properties across three samples differing in culture and HIV serostatus, and that
      condom use responsibility is conceptualized as a measure of general
      responsibility rather than as a reciprocal self/partner responsibility.

PMID- 17453577
TI  - Social-cognitive determinants of HIV risk-taking intentions among men who date
      men through the Internet.
AB  - The present study was set up to investigate social-cognitive determinants of HIV
      risk precautionary intentions among men who have sex with men (MSM), who meet sex
      partners on the Internet. Participants were enrolled through the major gay chat
      room in The Netherlands, www.chatboy.nl, and were asked to complete an online
      questionnaire. Theory of Planned Behaviour variables attitude, subjective norm,
      and perceived control explained 55% of the variance in intention to use condoms
      for anal sex with future e-dates. Adding descriptive norm, personal norm and
      anticipated regret explained 70%. Sexual fantasies and HIV-status had unique
      effects on intentions. Differences between high and lower intenders are
      presented. Limitations of the study are discussed and objectives for an
      intervention to promote condom use are given.

PMID- 17453578
TI  - A group-based intervention to increase condom use among HIV serodiscordant
      couples in India, Thailand, and Uganda.
AB  - This study assessed the feasibility of a group-based couples intervention to
      increase condom use in HIV serodiscordant couples in three countries (India,
      Thailand and Uganda). The intervention focused on communication, problem solving,
      and negotiation skills. Forty-three couples enrolled in the intervention (15 in
      India, 14 in Thailand, and 14 in Uganda) and 40 couples completed all study
      activities. Participants were interviewed at baseline and at one and three months
      post- intervention. The intervention consisted of two same sex sessions and two
      couples sessions with 'homework' to practice skills between sessions. The same
      intervention modules were used at each site, tailored for local appropriateness.
      Participants at each site were enthusiastic about the intervention, citing
      information about HIV serodiscordancy and the opportunity to meet couples 'like
      us' as important features. Participants reported increased comfort discussing sex
      and condoms with their partner, although some participants remain concerned about
      situations when condoms might not be used (e.g. when drunk). At three-month
      follow up 90% of the participants reported having been able to use the skills
      from the intervention with their partner. Our results highlight the feasibility
      of this couples group-based intervention and the need for ongoing support for
      discordant couples.

PMID- 17453579
TI  - Applicability of the theory of planned behavior to intended and self-reported
      condom use in a rural Ethiopian population.
AB  - This study aimed to assess the applicability of the Theory of Planned Behavior
      (TPB) in predicting intended and self-reported condom use and to examine the
      effect of previous condom use (PCE) among young adults in rural Ethiopia. A TPB
      interview was completed by 802 adults (mean age 20.7 years, 74.7% women) and 743
      adults (mean age 20.7 years, 76.4% women) reported use of condom at three-months
      follow-up. The TPB and PCE explained 36% and 2.2% of the variance in intended
      condom use. Subjective norms discriminated strongly between individuals with and
      without PCE. The TPB and PCE accounted for 5.3% and 8.5% of the variance in
      reported condom use. This study concludes that the TPB provided a fairly accurate
      description of the process underlying intention but was less sufficient to
      account for self-reported condom use. Ethiopian youth decided on condom use if
      they anticipated predominantly positive consequences associated with performance
      and social support, whereas perceived barriers seemed to have less impact. Once
      they had started to use condoms, they were more likely to continue to do so in
      the future.

PMID- 17453580
TI  - The best way to tell you to use a condom: the interplay between message format
      and individuals' level of need for cognition.
AB  - The present study addressed how individuals in high versus low need for cognition
      react to a persuasive message (concerning safer sexual conduct) presented either
      in a written format or in a comic-strip format. A control group that did not
      receive any persuasive message was also included. With reference to the Theory of
      Reasoned Action, we analyzed participants' instrumental attitude and instrumental
      norm toward the use of condoms. Results indicated that, compared to participants
      in the control group, providing participants with the persuasive message
      bolstered their instrumental attitude and norm. More importantly, participants
      high in need for cognition displayed higher levels of both instrumental attitude
      and norm when the message was in a written, as compared to a comic-strip, format.
      In contrast, participants low in need for cognition reported a stronger level of
      both instrumental attitude and norm in reaction to a comic-strip than a written
      message. Results are discussed with respect to their theoretical and practical
      implications.

PMID- 17453581
TI  - Self reported risk behaviour among injecting drug users: self versus assisted
      questionnaire completion.
AB  - The current study aimed to compare self-reported injecting and sexual risk
      behaviour among Needle and Syringe Program (NSP) attendees who self-completed a
      questionnaire to that of those who received assistance in completing the
      questionnaire. Information on demographic, injecting and sexual risk behaviour
      was collected via a self-completed questionnaire for an annual cross-sectional
      survey of injecting drug users (IDUs) recruited from sentinel NSPs around
      Australia. Assistance was provided when necessary and recorded. Of 2,035
      participants, 1,452 (71%) reported completing the questionnaire without
      assistance. Being male and nominating a language other than English spoken at
      home was independently associated with receiving assistance with questionnaire
      completion. Participants who reported heroin as the drug last injected were also
      more likely to receive assistance. Multivariate analyses revealed those who
      received assistance with questionnaire completion were less likely to report re
      using a syringe after someone else and less likely to report sex work in the past
      month. The current findings suggest self-completion of risk behaviour
      questionnaires should be considered as an alternative to interviewer administered
      questionnaires to maximise accuracy of self-reports.

PMID- 17453582
TI  - Time perspective and quality of life among HIV-infected patients in the context
      of HAART.
AB  - We explored associations between time perspective (TP) and quality of life (QOL)
      among HIV-infected patients. With the French validated version of the Zimbardo
      Time Perspective Inventory, we evaluated the TP of patients. A self-administered
      questionnaire gathered information about QOL (WHOQOL-HIV), TP, relationship with
      medical staff and self-reported side effects of HAART. Six scores of QOL -
      physical, psychological, social relationship, environment, patient independence
      and spirituality were used as dependent variables in the linear regressions to
      identify factors associated with QOL. The sample (n=72) for this study was
      recruited from a hospital department specialising in HIV care and consisted of 48
      (67%) HIV-infected women and 24 (33%) HIV-infected men with a mean age of 42
      years. Using hierarchical regression analysis adjusted on socio-demographic
      characteristics, clinical characteristics and co-factors, significant
      relationships were observed between the several TP orientations and an impaired
      physical, environmental QOL as well as level-of-independence QOL. Specific
      dimensions of QOL are influenced by specific orientations of TP, which provides
      information on self-perception and subjective evaluation of QOL. The TP construct
      provides keys to managing HIV infection in order to improve QOL.

PMID- 17453583
TI  - Estimating the impact of alcohol consumption on survival for HIV+ individuals.
AB  - Alcohol consumption is associated with decreased antiretroviral adherence, and
      decreased adherence results in poorer outcomes. However the magnitude of
      alcohol's impact on survival is unknown. Our objective was to use a calibrated
      and validated simulation of HIV disease to estimate the impact of alcohol on
      survival. We incorporated clinical data describing the temporal and dose-response
      relationships between alcohol consumption and adherence in a large observational
      cohort (N=2,702). Individuals were categorized as nondrinkers (no alcohol
      consumption), hazardous drinkers (consume > or =5 standard drinks on drinking
      days), and nonhazardous drinkers (consume <5 standard drinks on drinking days).
      Our results showed that nonhazardous alcohol consumption decreased survival by
      more than 1 year if the frequency of consumption was once per week or greater,
      and by 3.3 years (from 21.7 years to 18.4 years) with daily consumption.
      Hazardous alcohol consumption decreased overall survival by more than 3 years if
      frequency of consumption was once per week or greater, and by 6.4 years (From
      16.1 years to 9.7 years) with daily consumption. Our results suggest that alcohol
      is an underappreciated yet modifiable risk factor for poor survival among
      individuals with HIV.

PMID- 17453584
TI  - Occupational therapy for advanced HIV patients at a home care facility: a pilot
      study.
AB  - Occupational therapy holds promise to increase quality of life and social
      functioning in patients with HIV infection. Since 2000 through 2005, we
      experimented a complex structured intervention including directly administered
      HAART, psychiatric support and occupational therapy for 14 patients with advanced
      HIV infection and multiple disabilities, cared for at an Italian home care
      facility. Social and occupational abilities were evaluated using the Axis V of
      DMS-IV, as assessed by the Global Assessment of Functioning Scale. Patients'
      abilities in coping with stressful situations were examined using the Social
      Dysfunction Rating Scale. Both outcomes were evaluated in interviews at study
      entrance and yearly thereafter. As compared to baseline, social function mean
      score significantly increased by 42% after one year of follow-up, and social
      stress mean score was significantly reduced by 11%. Both outcomes continued to
      improve constantly during the entire follow-up. Acceptance of the intervention
      was high, and three patients got outdoor job positions. The findings from this
      pilot study suggest that occupational therapy could be integrated with success in
      the treatment of severely disabled patients with advanced HIV infection.
      Confirmation from further research is required.

PMID- 17453585
TI  - Acceptability of male circumcision for prevention of HIV infection in Zambia.
AB  - Numerous observational studies and three clinical trials have shown male
      circumcision (MC) to be partially protective against HIV acquisition in
      heterosexual men. This has led to consideration of introducing circumcision as an
      HIV prevention strategy in parts of sub-Saharan Africa. This study assesses the
      acceptability of male circumcision as an intervention to improve male genital
      hygiene and reduce sexually transmitted infections, including HIV-1 in Zambia.
      Thirty-four focus group discussions were conducted - 17 with men and 17 with
      women - in four districts chosen to represent urban and rural communities where
      circumcision is and is not traditionally practiced. In communities where
      circumcision is little practiced, the main facilitators for acceptance were
      improved genital hygiene, HIV/STI prevention, and low cost. The main barriers
      were cultural tradition, high cost, pain, and concerns for safety. If MC is
      proven to reduce risk for HIV and STIs, most participants reported that they
      would seek circumcision for themselves or their partners or their sons if it was
      free or at a minimal cost. Acceptability of male circumcision for STI and HIV
      prevention appears to be high in Zambia.

PMID- 17453586
TI  - Continuation with cotrimoxazole prophylaxis for the prevention of opportunistic
      infections in HIV-infected persons in rural Zimbabwe: feasibility, obstacles and
      opportunities.
AB  - We examined the outcomes of a World Health Organization (WHO) recommended
      programme offering cotrimoxazole (CTM) prophylaxis to 908 HIV-positive
      individuals in rural Zimbabwe, who accepted enrolment in the treatment programme.
      Outcomes included duration in programme, time between visits, relationship and
      marital status. Mean duration of participation in the programme was 224 days. The
      mean time between visits decreased from 11.2 weeks, between visit 1 and 2, to 4.3
      weeks between visit 11 and 12. Statistical analysis showed significant positive
      correlations between duration in programme and participant age, participant
      relationship status and the partner's state of affairs. Statistical analysis
      showed no significant correlation between duration in programme and gender.
      Results indicate that if continuation is demonstrated for the first 4 to 6
      months, participants will continue with the CTM programme. Results also reflect
      the constrained feasibility of CTM prophylaxis in rural Africa as well as the
      need to target subpopulations, such as young people, patients and their spouses
      for focused HIV/AIDS education initiatives.

PMID- 17453587
TI  - Long-term follow-up of uninfected children born to HIV-infected women and exposed
      to antiretroviral therapy: survey of parents' and health professionals' views.
AB  - Most uninfected children born to diagnosed HIV-infected women are now exposed to
      antiretroviral therapy (ART) in utero and neonatally and concerns have been
      raised over the safety of this exposure. To explore parents' and health
      professionals' views on the long-term follow-up of uninfected children two
      related surveys were conducted in the UK. Questionnaires were completed by 140
      parents/carers and 40 health professionals. Most of the respondents in both
      surveys (96% overall) acknowledged that it was important to follow up children to
      identify possible side effects from ART exposure. Almost all respondents (99%)
      found at least one of the strategies acceptable: follow-up through the clinic, by
      telephone, post or using data linkage. A third of parents and nearly half of
      health professionals strongly objected to at least one strategy, mostly postal
      and clinic contact respectively. The majority of parents (98%) thought they
      should be told if a potential health risk associated with ART exposure was
      identified; 73% of parents wanted any direct contact to be through them even when
      the child had grown up. Almost all respondents were supportive of the rationale
      for follow-up and, while expressing a preference for certain strategies,
      generally did not dismiss others. However, developing a single form of long-term
      follow-up which is both acceptable and feasible is challenging.

PMID- 17453588
TI  - Late presentation for HIV care in central Haiti: factors limiting access to care.
AB  - OBJECTIVE: Many patients with HIV infection present for care late in the course
      of their disease, a factor which is associated with poor prognosis. Our objective
      was to identify factors associated with late presentation for HIV care among
      patients in central Haiti. METHODS/DESIGN: Thirty-one HIV-positive adults,
      approximately 10% of the HIV-infected population followed at a central Haiti
      hospital, participated in this research study. A two-part research tool that
      included a structured questionnaire and an ethnographic life history interview
      was used to collect quantitative as well as qualitative data about demographic
      factors related to presentation for HIV care. RESULTS: Sixty-five percent of the
      patients in this study presented late for HIV care, as defined by CD4 cell count
      below 350 cells/mm3. Factors associated with late presentation included male sex,
      older age, patient belief that symptoms are not caused by a medical condition,
      greater distance from the medical clinic, lack of prior access to effective
      medical care, previous requirement to pay for medical care, and prior negative
      experience at local hospitals. Harsh poverty was a striking theme among all
      patients interviewed. CONCLUSIONS: Delays in presentation for HIV care in rural
      Haiti are linked to demographic, socioeconomic and structural factors, many of
      which are rooted in poverty. These data suggest that a multifaceted approach is
      needed to overcome barriers to early presentation for care. This approach might
      include poverty alleviation strategies; provision of effective, reliable and free
      medical care; patient outreach through community health workers and collaboration
      with traditional healers.

PMID- 17453589
TI  - Protease inhibitors and cardiovascular disease: analysis of the Los Angeles
      County adult spectrum of disease cohort.
AB  - Since protease inhibitors (PIs) were first introduced in 1995, research has shown
      that use of PIs greatly improves rates of survival, while slowing HIV disease
      progression. However, there are concerns that use of PIs may be associated with
      an increased risk of cardiovascular disease (CVD). To examine the relationship
      between PI use and CVD among HIV-infected patients, a large
      retrospective/prospective observational study was conducted. The study population
      was a clinic-based population seeking HIV treatment services between 1990 and
      2000 at several sites in Los Angeles County. CVD was defined as ischemic heart
      disease/coronary artery disease (ICD-9 codes 410-414, 428, and 429.7) and
      cerebrovascular disease/stroke (ICD-9 codes 430-438). Multiple imputation was
      performed on missing data, and survival analysis was performed on the imputed
      datasets using an extended Cox Proportional Hazards Model. The 5,667 HIV-infected
      individuals contributed 15,550 person-years of follow-up. Eighty incident cases
      of CVD were identified. Use of PIs (hazard ratio (HR)=6.22 [95% CI: 3.13-12.39],
      p-value <0.001) and time-dependent non-PI use (HR 3.18 [1.99-5.09], p<0.001) were
      associated with CVD. Clinicians should monitor treatment of HIV-infected patients
      for adverse CVD events, and consider alternate forms of drug therapy and CVD
      preventing drugs, particularly for those with a personal or family history of
      CVD.

PMID- 17453590
TI  - Barriers to access to medical cannabis for Canadians living with HIV/AIDS.
AB  - North American studies suggest that as many as one-third of people living with
      HIV/AIDS self-medicate with cannabis for relief of physical and stress-related
      symptoms. Although cannabis remains a controlled substance in Canada, legal
      access has been granted to people with HIV/AIDS and other serious illness under
      the Marihuana Medical Access Regulations (MMAR) since 2001. Several years into
      the programme, however, few Canadians ( approximately 1400) have obtained MMAR
      approval, suggesting that substantial obstacles remain. This paper reports
      findings from a 2005 survey (n=197) and focus groups conducted to identify
      barriers to access to medical cannabis among people living with HIV/AIDS. Most
      (86%) respondents who reported using cannabis as medicine continue to rely on
      illegal sources for their supply. They cited lack of information, product quality
      concerns, and an onerous, confusing application process among other problems
      mentioned with the MMAR. The findings are discussed in terms of policy
      suggestions for facilitating access to a legal source of cannabis for medical
      users.

PMID- 17453591
TI  - A randomised control trial of structured interrupted generic antiretroviral
      therapy versus continuous therapy in HIV-infected individuals in Southern India.
AB  - This randomised control trial, conducted in Chennai, India, compared structured
      interrupted therapy (SIT) and continuous therapy (CT) in relation to immunologic
      and virologic outcomes, adverse events (AEs) and cost of therapy. ART-naive adult
      HIV1-infected participants with CD4 counts 50-350 cells/mm(3), and plasma viral
      load (PVL)>5000 copies/mL were enrolled and placed on Indian-manufactured generic
      ART: zidovudine(AZT)/stavudine(d4T)+lamivudine(3TC)+efavirenz(EFV). After at
      least six months of continuous therapy, subjects were randomised to SIT (one-week
      on/one-week-off cycles) or CT. The primary end-point was the proportion of
      subjects maintaining CD4>200 cells/mm(3) at six and 12 months after
      randomisation. Secondary end-points were effective viral suppression (PVL<400
      copies/mL), AEs and cost. All analyses used intention-to-treat methodology. Of 40
      participants (69% male; mean age 36+/-7; median baseline CD4 and PVL: 162
      cell/mm(3)and 259,000 copies/mL), 17 were randomised to SIT and 18 to CT. At
      randomisation, median CD4s for SIT and CT were 378 cells/mm(3) and 357
      cells/mm(3), respectively. All participants had PVL<400 copies/mL at time of
      randomisation. Median CD4 six months after randomisation was 498 cells/mm(3) and
      417 cells/mm(3) for SIT and CT respectively. All participants had CD4>200
      cells/mm(3). One participant on CT and two on SIT had sustained PVL>400
      copies/mL. There were no serious AEs or deaths. Structured interrupted therapy
      cost was half of CT. Structured interrupted therapy was effective at maintaining
      CD4 above 200 cells/mm(3). Adverse events were comparable in both groups, with
      50% reduction in cost for SIT. Further research on such strategies may benefit
      resource-constrained settings.

PMID- 17453592
TI  - Differences between HIV-positive gay men who 'frequently', 'sometimes' or 'never'
      engage in unprotected anal intercourse with serononconcordant casual partners:
      positive Health cohort, Australia.
AB  - By measuring the actual number of risk acts engaged in by HIV-positive men
      participating in the Positive Health (PH) cohort study, this paper sets out to
      document the distribution of risk acts, to report on the proportion of acts of
      unprotected anal intercourse with casual (UAIC) partners that occurred between
      HIV-positive men (i.e. seroconcordant positive) and to examine the factors that
      differentiated men who 'frequently' compared with 'sometimes' or 'never' engaged
      in unsafe UAIC (i.e. UAIC with serononconcordant partners: partners who have not
      tested positive for HIV). The findings show that 42.6% of all UAIC acts occurred
      between seroconcordant HIV-positive partners, posing no risk of HIV infection to
      an HIV-negative person. A minority of participants (10%) accounted for the
      majority (70.7%) of the unsafe acts of UAIC. The HIV-positive men who 'sometimes'
      engaged in unsafe UAIC had higher treatment optimism scores and were more likely
      to use Viagra in comparison with those who did not engage in such risk. Those who
      reported 'frequent' engagement in unsafe UAIC were more likely to engage in a
      range of esoteric sexual practices, be slightly less well educated and be taking
      antiretroviral therapy compared with HIV-positive men who 'sometimes' engaged in
      unsafe UAIC. As such, taking ART but not viral load, predicted frequent unsafe
      UAIC. When considered alongside earlier studies, these results suggest that HIV
      negative men who engage in esoteric sexual practices may be at increased risk of
      HIV transmission, not necessarily because they engage in esoteric sex practices
      but because of the sub-cultural milieu in which esoteric sex is occurring. The
      findings from this study also endorse the measurement of UAIC acts as a useful
      gauge of risk.

PMID- 17453593
TI  - Differential improvement in survival among patients with AIDS after the
      introduction of HAART.
AB  - We explored changes in the survival of patients with AIDS (PWA) according to the
      availability of antiretroviral drugs (1994-2002). We tested whether changes in
      the hazard ratio of progression to death (HR) have been homogeneous among various
      groups of PWA. We included 4158 PWA diagnosed in Paris, notified to the French
      National Surveillance Institute by 2002. Four calendar periods were defined:
      monotherapy (1994-95), bitherapy-HAART transition (1996), early HAART (1997-99),
      late HAART (2000-October 2002). HR were calculated with Cox models, including the
      calendar period, modelled as a time dependent covariate. Models were stratified
      by age, transmission category, CD4 cell count, and AIDS-defining illnesses (ADI)
      group. Cumulative survival at 60 months increased from 44.0% (before July 1996)
      to 75.6% (after July 1996) and median survival increased from 31.9 months to >76
      months. Adjusted HR reached a minimum in the late HAART period (HR 0.22, 95% CI:
      0.19-0.26). No difference in the decrease of the HR has been found by age. HR
      decreased and was marked during the late HAART period across all HIV transmission
      categories, including intravenous drug use. HR decreased significantly for all
      ADIs groups, including tumours. Among PWA diagnosed with tuberculosis, the HR
      decreased significantly only in the late HAART period. HR decrease was stronger
      for PWA with a CD4 cell count < or =200/mm(3). Substantial improvements in
      survival after the introduction of HAART were found for all PWA but varied by
      specific ADIs and the degree of immunosuppression.

PMID- 17453594
TI  - Oral health needs of HIV/AIDS orphans in Gauteng, South Africa.
AB  - To care for HIV/AIDS orphans will put health and social services in South Africa
      before a major challenge. Published clinical information on South and Southern
      African HIV-positive children is limited to hospitalized children. A cross
      sectional, prospective study was conducted on a convenience sample of HIV
      positive children, living in orphanages in Gauteng, South Africa, in order to
      determine the oral health needs of the children. Five homes for
      abandoned/orphaned HIV/AIDS children were visited, 11 caregivers, excluding the
      nursing sisters (registered nurses), were interviewed to determine their
      knowledge regarding oral health. An oral examination was performed on 87 children
      who were not receiving antiretroviral treatment. The caregivers were
      knowledgeable regarding pseudomembranous candidiasis but all lacked knowledge on
      oral hygiene procedures and the cariogenic potential of a baby bottle. The mean
      age of the children ranged between 3.2 and 7 years, with one home having children
      older than 11 years. Rampant early childhood caries in 19 (21.8%) children was
      the major finding, with 5 children suffering severe pain from multiple carious
      teeth. In the hospice section of the homes all 12 children had clinically
      detectable candidiasis, while in 4 (33.3%) there was an associated bleeding and
      ulceration of the oral mucosa, impairing their ability to eat. The findings
      indicate a training need among caregivers regarding the oral health of children
      and a role for health professionals in preventing oral diseases and reducing
      suffering.

PMID- 17453595
TI  - The Evolution of HIV illness representation among marginally housed persons.
AB  - Many HIV-infected marginally housed individuals have difficulty engaging in
      health care. To investigate HIV health-related behaviour, 14 in-depth interviews
      with marginally housed HIV-infected individuals were conducted and analysed
      utilizing standard qualitative methodologies. The analysis was based on the
      Illness Representation Model, which describes five conceptual dimensions of
      illness: identification; cause; timeline; management; and consequences. A
      theoretical model of illness representation at two distinct time points emerged
      and included the two categories: 'didn't suspect and didn't believe it' and 'knew
      but needed proof'. In this study illness representation categories were found to
      evolve and change over time, and were associated with engagement in HIV care.
      This study may help guide programmes that focus on enhancing health-promoting
      behaviour and improving engagement in health care among marginally housed
      individuals.

PMID- 17453596
TI  - The effect of homelessness on hospitalisation among patients with HIV/AIDS.
AB  - The purpose of this study was to determine the effect of homelessness on the
      costs and patterns of hospitalisation in patients with HIV/AIDS. A retrospective
      longitudinal study design, based on medical records data covering 2,768 person
      years of observation between 1997 and 2003 on patients with HIV/AIDS, was
      employed. A contextual measure of neighbourhood socioeconomic status (SES) was
      also used to uncover differences among low- and high-SES neighbourhood dwellers.
      The association of homelessness and neighbourhood SES with total annual
      hospitalisation costs, length of stay, numbers of hospital and emergency
      department admissions and the probability of an operating room procedure,
      controlling for other covariates, was assessed using multivariate regression
      analysis. Our results suggest that the homeless and low-SES neighbourhood
      residents had a large proportion of total costs attributable to admissions for
      acute events related to the progression of disease. Hospitalisations for planned
      operating room procedures comprised a relatively larger proportion of
      hospitalisation costs for high-SES neighbourhood residents. One implication of
      our findings is that improvements in the continuity of care and cost savings on
      inpatient care may be realised through further development of social assistance
      programs aimed at reaching the homeless and residents of low-SES neighbourhoods.

PMID- 17453597
TI  - Community perspectives on care options for HIV prevention trial participants.
AB  - There is on-going global debate and policy-setting concerning researchers'
      obligations to meet the health needs of people participating in HIV prevention
      trials in resource-poor settings. The perspectives of local community
      stakeholders on this issue are poorly understood as most of what is presented on
      behalf of communities where research takes place is anecdotal commentary. Using
      qualitative methods (130 in-depth interviews and 20 focus groups) we assessed
      perceived fairness of different strategies to meet the health needs of women who
      become HIV-infected during a hypothetical vaginal microbicide trial. Respondents
      included HIV prevention research participants, community stakeholders and health
      care service providers in ten sites in seven countries (South Africa, Malawi,
      Tanzania, Zimbabwe, Zambia, India, US). Many respondents perceived referrals to
      be a potentially fair way to address care and treatment needs but concerns were
      also voiced about the adequacy of local health-care options and the ability of
      trial participants to access options. Most respondents viewed the provision of
      antiretroviral treatment by researchers to HIV-infected trial participants as
      unfair if treatment was not sustained beyond the end of the trial. The results
      underscore the importance of effectively linking trial participants to
      sustainable, community-based treatment and care.

PMID- 17453598
TI  - Preliminary findings of an intervention integrating modified directly observed
      therapy and risk reduction counseling.
AB  - Various interventions have been proposed to address these ongoing needs of HIV
      positive patients as they encounter challenges with medication adherence and risk
      reduction. This report presents the findings of a study that pilots 'DAART+', an
      intervention that integrates modified directly observed therapy (MDOT), and risk
      reduction counseling for a population of marginally housed, substance-using
      persons. The pilot study intended to assess the feasibility of the intervention
      and to obtain data to assess the intervention's potential effectiveness. The
      preliminary data reveal that 83% of participants who completed the intervention
      (n=18) had undetectable viral load (VL) (VL< or =400 copies/mL) which represents
      a 2.15 log(10) decrease from baseline. Risk behaviors also changed modestly with
      self-reported increases in condom usage.

PMID- 17453599
TI  - A study on burnout syndrome in healthcare providers to people living with HIV.
AB  - Dedicating physical and psychological care to other people is a tiring activity,
      not only because of the responsibility but also, more importantly, because of the
      emotional aspects involved in this relationship, which lead to stress and, if
      this stress continues, to burnout syndrome. Some authors report that the demands
      of caring for HIV-positive people are greater than those for other types of
      patients, increasing the chances of burnout. This study aimed to investigate the
      occurrence of burnout in healthcare providers of HIV-positive patients in the
      state of Parana, Brazil. Through the use of a questionnaire and the Maslach
      Burnout Inventory (MBI), 87 people were evaluated. The averages for the MBI were
      19.07 for emotional exhaustion (EE), 4.18 for depersonalisation (DE) and 39.60
      for personal accomplishment (PA). There were 26.4% of people with high scores on
      EE, 17.2% presenting elevated DE and 10.5% showing diminished PA in their work.
      It was observed that the majority of the carers were in this occupation for a
      short period of time (74.7% for less than five years), while 42.5% spent up to 20
      hours per week in the activity. Among the healthcare providers, 63.2% were
      volunteers. The variables 'sex' and 'working time' have showed themselves as
      significant predictors for DE as well as 'age' for PA. Taking these
      characteristics into account, it can be seen that it is necessary to give some
      special attention to this group of workers, in order to enable them to access
      preventive and/or interventional measures.

PMID- 17453600
TI  - HIV testing and disclosure: a qualitative analysis of TB patients in South
      Africa.
AB  - In South Africa, more than 60% of TB patients have HIV co-infection. Voluntary
      counseling and testing (VCT) is critical to effective HIV prevention, and TB
      facilities are optimal venues for delivery of these services. This study employed
      qualitative research methods to explore the decision-making processes for HIV
      testing and serostatus disclosure by 21 patients hospitalized with
      multi/extensively-drug resistant TB (M/XDR-TB) in Durban, KwaZulu Natal. Data
      collected from in-depth interviews characterized 3 broad themes: HIV testing
      history, experiences and perceptions of stigma and disclosure, and the
      relationship between TB and HIV/AIDS. Fear of AIDS-related stigma, the singular
      stress of TB infection, the absence of partner's consent, asymptomatic or
      incurable disease, and uncertainty about subsequent eligibility for
      antiretroviral treatment while still receiving TB treatment were identified as
      potential barriers to the uptake of VCT. HIV serostatus disclosure was impeded by
      the felt stigma of a 'discreditable' infection, manifested by social rejection
      and discrimination. The public disclosure of TB illness helped relieve some co
      infected patients' overall burden of stigma through a process of 'covering'. HIV
      prevention [corrected] measures such as VCTare likely to be more effective within
      TB facilities if greater sensitivity is paid to TB patients' specific social
      issues and perceptions. These patients are not only at greater risk for HIV co
      infection but also for experiencing the double stigma of TB and HIV/AIDS.

PMID- 17453602
TI  - ADHD and substance use disorders: developmental aspects and the impact of
      stimulant treatment.
AB  - Adolescents and adults with substance use disorders often demonstrate symptoms of
      inattention, impulsivity, and hyperactivity. These core symptoms of ADHD may
      contribute to the development of substance use disorders by promoting antisocial
      behavior and substance use; conversely, substance use itself can adversely affect
      these symptoms. Common deficits in self-regulatory processes could underlie the
      developmental progression of these disorders, deficits further worsened by
      ongoing substance use. Some investigators have questioned whether stimulant
      treatment itself could promote substance abuse, while others have argued that
      such treatment reduces substance abuse. With an increased awareness of the
      phenomenon of adult ADHD and its relevance to substance-abusing persons, there is
      an increased awareness of the potential benefit of ADHD treatment on substance
      abuse treatment outcome. Consideration of an individual's developmental
      relationship between attention deficit/hyperactivity symptoms and substance use
      can inform treatment planning among patients seeking substance abuse treatment.

PMID- 17453603
TI  - Do individuals with ADHD self-medicate with cigarettes and substances of abuse?
      Results from a controlled family study of ADHD.
AB  - Studies report increased rates of cigarette and substance use in youths with
      Attention-Deficit/Hyperactivity Disorder (ADHD), though the mechanism of risk
      remains unclear. The present study tests the hypothesis that ADHD individuals
      "self-medicate" with cigarettes and substances of abuse. As part of five- and ten
      year case-control longitudinal family studies of ADHD, responses to the Drug Use
      Screening Inventory (DUSI) were examined for evidence of self-medication. DUSI
      data from 90 ADHD probands and 96 control probands were obtained. Thirty-six
      percent of subjects reported self-medication, 25% used to get high, and 39% had
      unknown motivation. No significant differences were found between ADHD and
      controls in motivation. ADHD symptoms did not differ between self-medicators and
      subjects using to get high. DUSI problem scores were higher in ADHD (versus
      controls), those using to get high (versus self-medicators), and subjects using
      alcohol (versus other substances). More than one-third of adolescents and young
      adults endorsed using cigarettes and substances for self medication. Studies
      clarifying the role of self-medication in substance use disorders are necessary.

PMID- 17453604
TI  - Substance use among ADHD adults: implications of late onset and subthreshold
      diagnoses.
AB  - Diagnosing ADHD in adults is difficult when the diagnostician cannot establish an
      onset prior to the DSM-IV criterion of age seven or if the number of symptoms
      does not achieve the DSM threshold for diagnosis. These diagnostic issues are an
      even larger concern for clinicians faced with adults with substance use disorders
      (SUD). The present study compared four groups of adults: full ADHD subjects who
      met all DSM-IV criteria for childhood onset ADHD, late onset ADHD subjects who
      met all criteria except the age at onset criterion, subthreshold ADHD subjects
      who did not meet full symptom criteria, and non-ADHD subjects who did not meet
      any of the above criteria. Diagnoses were by the Structured Clinical Interview
      for DSM-IV, and the Drug Use Severity Index (DUSI) was used for self-report of
      substance use. Cigarette and marijuana use was significantly greater in all ADHD
      groups relative to non-ADHD controls. Although usage rates of other drugs failed
      to reach significance, the ADHD groups were more likely to have used each drug
      (except alcohol) compared with the non-ADHD group. The late onset and full ADHD
      groups were more likely to have endorsed ever having a problem due to use of
      cigarettes, alcohol, or marijuana and reported more trouble resisting use of
      drugs or alcohol. The full ADHD group was more likely than the other groups to
      have reported "getting high" as their reason for using their preferred drug.
      Adults with ADHD have elevated rates of substance use and related impairment.
      Data about late onset ADHD provides further support for the idea that the DSM-IV
      age at onset criterion is too stringent. In contrast, subthreshold ADHD seems to
      be a milder form of the disorder, or perhaps a heterogeneous group of true ADHD
      cases and false positives.

PMID- 17453605
TI  - Abuse liability of medications used to treat attention-deficit/hyperactivity
      disorder (ADHD).
AB  - The use of psychostimulants to treat attention-deficit/hyperactivity disorder
      (ADHD) has been controversial for a number of reasons. In an effort to clarify
      the extent to which the psychostimulant methylphenidate has abuse potential, the
      existing published evidence has been reviewed and is summarized here, with an
      emphasis on delineating a number of related but independent issues that are often
      confused. The existing evidence reviewed is pertinent to three questions: Does
      stimulant drug use increase the risk for substance abuse later in life? Do ADHD
      medications have the potential for abuse?, and What is the distinction between
      drug abuse and misuse/diversion with respect to ADHD medication?

PMID- 17453607
TI  - Neurobiology of cocaine addiction: implications for new pharmacotherapy.
AB  - The development of pharmacotherapies for cocaine addiction has been
      disappointingly slow. However, new neurobiological knowledge of how the brain is
      changed by chronic pharmacological insult with cocaine is revealing novel targets
      for drug development. Certain drugs currently being tested in clinical trials tap
      into the underlying cocaine-induced neuroplasticity, including drugs promoting
      GABA or inhibiting glutamate transmission. Armed with rationales derived from a
      neurobiological perspective that cocaine addiction is a pharmacologically induced
      disease of neuroplasticity in brain circuits mediating normal reward learning,
      one can expect novel pharmacotherapies to emerge that directly target the
      biological pathology of addiction.

PMID- 17453606
TI  - Treatment strategies for co-occurring ADHD and substance use disorders.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common co-occurring mental
      disorder among patients with substance use disorders (SUD). Clinicians must be
      cognizant of the complicated nature of diagnosis and treatment of ADHD when
      comorbid with SUD. Pharmacotherapy remains the mainstay of treatment for ADHD,
      although complementary psychotherapeutic approaches have been developed.
      Psychostimulant medications are the most commonly used medications to treat ADHD,
      but many clinicians are reluctant to prescribe stimulants to patients with SUD.
      Recommendations for treatment planning and clinical management for patients with
      co-occurring ADHD and SUD are discussed.

PMID- 17453608
TI  - Methamphetamine use in rural Midwesterners.
AB  - Methamphetamine use has been characterized as a "rural" drug; however, little is
      known about rural methamphetamine use disorders (MUD). This study describes and
      compares characteristics of rural and urban patients with MUD. Rural study
      participants reported earlier first regular use of methamphetamine, more
      alcoholism, more intravenous use, and a greater number of cigarettes/day, and
      were more likely to report methamphetamine-related psychotic symptoms. Rural
      methamphetamine users report multiple factors that may contribute to medical and
      psychiatric complications and worsen their prognosis. This is of significant
      concern given the limited substance abuse, mental health, and specialty care
      available in most rural Midwestern communities.

PMID- 17453609
TI  - The relationship of self-esteem and self-efficacy to treatment outcomes of
      alcohol-dependent men and women.
AB  - This study investigates whether self-esteem is associated with clinical and
      demographic characteristics, self-efficacy expectancies, and post-treatment
      drinking outcomes. Forty-one (40.6%) women and 60 (59.4%) men were recruited
      during inpatient alcohol dependence treatment. At baseline, lower self-esteem was
      significantly associated with current depression and other psychiatric disorders.
      Self-esteem was not related to gender, relapse, other one-year drinking outcomes,
      or self-efficacy. Age and psychiatric disorders were strong predictors of self
      esteem at follow-up. This study suggests that different perceptions of the self
      have unique roles in recovery from alcohol use disorders.

PMID- 17453610
TI  - Sexual abuse and the outcome of addiction treatment.
AB  - The objective of this prospective follow-up study was to examine the effects of
      sexual abuse on substance use disorder patients' clinical presentation and course
      in treatment. Consecutive admissions to the MUHC's Addictions Unit were assessed
      at intake (N=206) and six-month follow-up (n=172). Assessments evaluated socio
      demographic and psychiatric characteristics, addiction severity, and physical
      and/or sexual abuse histories. Upon entering treatment, 23% reported prior sexual
      abuse with or without physical abuse. Patients with a sexual abuse history had
      higher rates of psychological problems, stronger family histories of substance
      use disorders, and more impaired family relationships. At six months, there were
      no differences between patients with and without sexual abuse histories in their
      response to treatment, or their utilization of treatment services. The current
      study failed to show that prior sexual abuse compromised short-term treatment
      outcomes.

PMID- 17453611
TI  - Correlates of severity of smoking among persons with severe mental illness.
AB  - Individuals with schizophrenia and severe mental illness smoke cigarettes at
      rates that well exceed the general population. Little is known about the
      correlates and sequelae of increased smoking severity on persons with severe
      mental illness. A total of 304 smokers from six community mental health centers
      were assessed for smoking history, psychiatric symptoms, co-occurring disorders,
      subjective quality of life, and expired carbon monoxide (CO). Statistical
      analyses identified correlates of smoking severity, as assessed by number of
      cigarettes smoked per week. The average number of cigarettes smoked per week was
      136+/-83. Increased smoking was associated with higher levels of expired CO and
      being Caucasian, and with a greater likelihood of a current diagnosis of
      hypertension and oral/gum disease. Greater smoking severity was also associated
      with greater perceived stress, poorer overall subjective quality of life, and
      lower satisfaction with finances, health, leisure activities, and social
      relationships. This study confirms high rates of heavy smoking among persons with
      severe mental illness. The association of increased quantity of cigarettes smoked
      with being Caucasian is consistent with previous reports in mentally ill and non
      mentally ill populations. The linkage of heavy smoking with poorer quality of
      life and co-occurring medical disorders suggests the importance of smoking
      reduction and cessation strategies to reduce smoking and decrease patients' total
      pack years of smoking.

PMID- 17453612
TI  - Brief intervention for students with methamphetamine use disorders: a randomized
      controlled trial.
AB  - This study evaluated the short-term (eight-week) benefits of brief intervention
      (BI) in students aged 14-19 years old who met the DSM-IV diagnostic criteria for
      methamphetamine (MA) dependence or abuse. The participants were randomly assigned
      to receive two 20-minute sessions of BI or one 15-minute session of
      psychoeducation (PE). Primary outcomes of interest were the decrease of MA use in
      days of use (per week) units and MA tablets used (per day when used). All
      outcomes were assessed at baseline (week 0), week 4, and week 8 (endpoint). A
      total of 48 participants were enrolled in the study (24 on BI and 24 on PE
      treatment). At week 4, the numbers of dropouts in the BI and PE groups were 7 and
      5, respectively. The frequency and amount of MA use decreased significantly in
      both groups. At week 8, the days of MA use had decreased in the BI group by a
      significantly larger number than in the PE group (t=2, df=34, p=0.04). BI appears
      to have some minimal short-term benefits for adolescents with MA use disorders.
      It may decrease the number of days that MA is used.

PMID- 17453613
TI  - Substance-abusing physicians: monitoring and twelve-step-based treatment.
AB  - This study was designed to provide an independent evaluation of the oversight and
      rehabilitation of substance-impaired physicians. Records of 104 physicians who
      had completed their monitoring period by the New York State Committee on
      Physicians' Health were selected at random from CPH files. They had been followed
      for an average of 41.3 months. Practice characteristics and substance use before
      admission, as well as workplace monitoring, twelve-step attendance, urine
      toxicologies, and relapse incidence after admission are reported. Significant
      intercorrelations among these variables were ascertained by logistic regression.
      The utility of twelve-step-based rehabilitation as part of a treatment plan for
      sustaining abstinence and averting relapse is discussed.

PMID- 17453614
TI  - High abstinence rates in heroin addicts by a new comprehensive treatment
      approach.
AB  - In this multi-center, naturalistic study, the effectiveness of naltrexone
      maintenance combined with the Community Reinforcement Approach (CRA) was
      investigated in detoxified, opioid-dependent patients (N=272). Patients were
      recruited from methadone maintenance programs. With intention-to-treat analysis,
      10 months of treatment yielded abstinence rates of 28% and 32% at 10 and 16
      months after detoxification. The cumulative abstinence rate at 16 months was 24%.
      Quality of life, craving, general psychopathology, use of other psychoactive
      substances, and addiction severity of the abstinent group significantly improved
      when compared to the relapsed group. This abstinence-oriented approach appears to
      be a feasible goal, and remains an important option next to long-term methadone
      maintenance in the management of opioid dependence.

PMID- 17453616
TI  - Colorblindness: a missed opportunity to address the negative impact of being
      black in America.

PMID- 17453615
TI  - Stepped care for mandated college students: a pilot study.
AB  - In the past decade, colleges and universities have seen a large increase in the
      number of students referred for the violation of alcohol policies. Stepped care
      assigns individuals to different levels of care according to treatment response,
      thereby maximizing efficiency. This pilot study implemented stepped care with
      students mandated to attend an alcohol program at a private northeastern
      university. High retention rates and participant satisfaction ratings suggest the
      promise of implementing stepped care with this population. Considerations for
      future applications of stepped care with mandated students are discussed.

PMID- 17453618
TI  - Gabapentin in comorbid anxiety and substance use.

PMID- 17453620
TI  - Alpha2-macroglobulin is a potential facilitator of prion protein transformation.
AB  - Cellular prion protein changes conformation during transformation to an
      infectious scrapie isoform. One measure of transformation is the development of
      partial resistance to protease treatment. A fraction of human and bovine plasma
      was identified containing activity that facilitates transformation of cellular
      prion protein to a protease resistant isoform in the presence of RNA in the
      absence of seeded scrapie prion protein. Purification of proteins from this
      fraction led to the identification of alpha2-macroglobulin as an active component
      suggesting that it may facilitate conformational changes in prion protein in
      spontaneous forms of prion disease.

PMID- 17453619
TI  - Codeine cough syrup use among sexually active, African-American high school
      youths: why Southern males are down to have sex.

PMID- 17453621
TI  - Cerebral AL lambda-amyloidoma: clinical and pathomorphological characteristics.
      Review of the literature and of a patient.
AB  - BACKGROUND: Amyloid deposits within the brain can be found in a heterogeneous
      group of diseases. Some of them involve only the central nervous system (AD);
      others are of systemic origin. Isolated deposits either in the brain, cranial
      nerves or within the spinal neural structures are extremely rare. So far, we do
      not know the natural origin, nor the clinical course. METHODS: We reviewed the
      overall published cases as far as available and added our own case to learn more
      about the natural history, clinical and imaging characteristics of this rare
      brain lesion. RESULTS: Together with our own case, 27 patients with cerebral
      amyloidoma were collected in the literature. The lesion always occurred
      supratentorially, moreover in another two cases also infratentorially. The
      initial symptoms as well as the results of different neuroimaging features were
      not specific. There was no predominance for sex and localization. Diagnosis could
      only be established by histopathological examination after surgical intervention.
      No recurrence was seen after radical resection; but there was progression in some
      cases of tumor biopsy. CONCLUSION: Complete surgical removal of cerebral AL
      amyloidoma seems to be the only way to prevent progression or recurrence of such
      a brain lesion.

PMID- 17453622
TI  - Heparan sulfate as a therapeutic target in amyloidogenesis: prospects and
      possible complications.
AB  - Amyloid formation in vivo is a much more complicated process than studies of in
      vitro protein/peptide fibrillogenesis would lead one to believe. Amyloidogenesis
      in vivo involves multiple components, some no less important than the
      amyloidogenic protein/peptides themselves, and each of these components, and its
      role in the pathogenetic steps toward amyloid deposition could, theoretically, be
      a therapeutic target. Herein we use the definition of amyloid as it was
      originally described, discuss the similarities and differences between amyloid in
      vivo and in vitro, address the potential role of the extracellular matrix in in
      vivo amyloidogenesis by focusing on a specific component, namely heparan sulfate
      proteoglycan, and describe studies illustrating that heparan sulfate is a valid
      target for anti-amyloid therapy. In light of experimental and recent clinical
      results obtained from studies addressing heparan sulfate's role in amyloid
      deposition additional novel anti-amyloid therapeutic targets will be proposed.
      Lastly, given the multiple roles that heparan sulfate plays in organ development,
      and organ and cell function, potential side effects of targeting heparan sulfate
      biosynthesis for therapeutic purposes are considered.

PMID- 17453623
TI  - Liver transplantation and anemia in familial amyloidosis ATTR V30M.
AB  - Familial amyloid polyneuropathy type I (FAP-I) is caused by a mutant
      transthyretin (TTR V30M) produced by liver, and orthotopic liver transplantation
      (OLT) is a widely accepted treatment for stopping the major production of TTR
      V30M. Anemia affects 24.8% of symptomatic FAP-I patients with low erythropoietin
      (Epo) levels, suggesting a blockage of Epo-producing cells by local or
      circulating factors. To evaluate the putative toxicity effect of the mutant
      protein on Epo-producing cells and consequent Epo production, clinical and
      laboratory parameters of 20 FAP patients were collected before and after liver
      transplantation, analyzed and compared. Following OLT, the prevalence of anemia
      increased, with a significant decrease in transferrin saturation, but without
      significant change in ferritin. Serum Epo levels remained low after OLT and the
      observed to expected (O/E) Epo level ratio decreased even further after OLT (O/E
      < 0.8 rose to 70%). Despite the decrease in creatinine clearance (95.1 to 66.9
      ml/min, p < 0.001), a similar median O/E Epo level was observed, independently of
      the presence of renal failure, excluding an important impact of renal failure on
      Epo production. The increase of anemia after OLT and the maintenance of a
      defective endogenous Epo production after liver transplantation excluded an
      inhibitory effect of the circulating TTR V30M on the Epo-producing cells.

PMID- 17453624
TI  - Humoral immune responses to peptides derived from the beta-amyloid peptide C
      terminal sequence.
AB  - There is a continuing interest in the immunochemical quantification of isoforms
      of amyloid beta-peptide (Abeta) in body fluids of patients with Alzheimer's
      disease (AD); however, at present there is no general procedure to produce and
      test the required antibodies. We examined various methods to generate rabbit anti
      Abeta; antibodies that are specific for Abeta(38), Abeta(40) and Abeta(42), and
      we tested their specificity and sensitivity by ELISA and Western blotting. To
      produce high-affinity antibodies required repeated inoculations of small doses of
      peptide conjugates over a period of at least 6 months. Antibodies generated to
      peptides derived from the Abeta(42) sequence showed some cross-reactivity with
      Abeta(40), but antibodies generated to Abeta4 peptides did not cross-react with
      Abeta(42). The shortest peptide capable of generating antibodies of moderate
      affinity possessed the sequence Met(35)-Ala(42); however, antibodies raised to
      the peptide Gly(33)-Ala(42) possessed the greatest affinity (K(D) = 1 nM) and
      specificity for Abeta(42). The latter antibodies were over 50,000-fold more
      reactive with Abeta(42) than with Abeta(40). They can detect Abeta isoforms in
      extracts of normal brain, where the peptides are present at levels below one part
      per billion. Our results provide methods to generate and characterize the
      specificity and affinity of anti-Abeta antibodies. This information is necessary
      to develop sensitive and specific immunoassays to quantify Abeta isoforms in
      brain extracts and in body fluids.

PMID- 17453625
TI  - Cellular events associated with the initial phase of AA amyloidogenesis: insights
      from a human monocyte model.
AB  - Reactive amyloidosis is a systemic protein deposition disease that develops in
      association with chronic inflammation. The deposits are composed of
      extracellular, fibrillar masses of amyloid A (AA) protein, an N-terminal fragment
      of the acute-phase serum protein serum amyloid A (SAA). The pathogenic conversion
      of SAA into amyloid has been studied in two human cell culture models, peritoneal
      cells and peripheral blood monocytes. Human monocyte cultures proved more robust
      than either mouse or human peritoneal cells at initiating amyloid formation in
      the absence of a preformed nidus such as amyloid-enhancing factor and
      particularly well suited for examination of individual cells undergoing amyloid
      formation. Amyloid-producing monocyte cultures were stained with Congo red and
      Alcian blue for detection of amyloid and glycosaminglycans, respectively;
      immunocytochemistry was performed to identify SAA/AA, CD68, CD14, lysosomal
      protein Lamp-1, and early endosomal protein EEA1. SAA interaction with monocytes
      was also visualized directly via fluorescence confocal microscopy. Amyloid was
      initially detected only in intracellular vesicles, but with time was seen
      extracellularly. Morphologic changes in lysosomes were noted during the early
      phase of amyloid formation, suggesting that exocytosis of fibrils may occur via
      lysosome-derived vesicles. Cultures engaged in amyloid formation remained
      metabolically active; no cytotoxic effects were observed. Mimicking in vivo
      phenomena, amyloid formation was accompanied by increased glycosaminoglycan
      content and C-terminal processing of SAA. The ability of human monocytes to
      endocytose and intracellularly transform SAA into amyloid via a mechanism that
      requires and maintains, rather than compromises, metabolic activity distinguishes
      them as a useful model for probing earliest events in the disease process.

PMID- 17453626
TI  - A new transthyretin variant (Glu61Gly) associated with cardiomyopathy.
AB  - We report the identification of a new transthyretin (TTR) gene mutation and
      variant protein, Glu61Gly, in a 55-year-old man with progressive cardiomyopathy,
      mild peripheral neuropathy and bilateral carpal tunnel syndrome. A diagnosis of
      TTR-associated familial amyloidosis (ATTR) was considered after an endomyocardial
      biopsy revealed amyloid deposits in the heart of a patient who had no family
      history of amyloidosis and no evidence of a plasma cell dyscrasia. Serum
      screening for a TTR variant by isoelectric focusing (IEF) was positive and
      prompted further studies to identify the genetic abnormality and to characterize
      the amyloidogenic protein. Direct DNA sequence analysis of all four coding
      regions in the TTR gene demonstrated heterozygosity in exon 3. Near equal amounts
      of guanine (G) and adenine (A) were observed at the second base position of codon
      61. The wild-type (GAG) and mutated (GGG) sequences found in codon 61 correspond
      to glutamic acid (Glu) and glycine (Gly) residues, amino acids which differ in
      mass by -72 Da. Mass spectrometric analyses of TTR immunoprecipitated from serum
      showed the presence of both wild-type and variant proteins. The observed mass
      results for the wild-type and variant proteins were consistent with the predicted
      values calculated from the genetic analysis data.

PMID- 17453627
TI  - The molecular mechanisms of the anti-amyloid effects of phenols.
AB  - Previous investigations demonstrated that various aromatic compounds, many of
      which are known antioxidants, inhibit amyloid fibril formation. Yet, the
      mechanism of action of these compounds is not fully understood and contribution
      of their antioxidative potency has not been addressed. In recent publications,
      Ono et al. (2003, 2004) studied the anti-amyloid effects of 11 phenols on each of
      three consecutive processes: (1) seeding (formation) of nascent fibrils, (2)
      elongation (extension) of the fibrils, and (3) depolymerization (destabilization)
      of the formed assemblies. The aim of the present study was to evaluate the
      molecular mechanisms that mediate the effects of the studied inhibitors on each
      of these processes. Hierarchical clustering analyses indicated that the studied
      inhibitors can be categorized into three groups: 'slightly active' inhibitors,
      'highly active' inhibitors and 'selective inhibitors' that differ markedly in
      their effects on these three stages. Analyses of the correlations between the
      effects of the studied compounds on the various stages of amyloid fibril
      formation, and their known physicochemical properties provided novel insights on
      the specific role of hydrophobic and aromatic interactions as well as the
      antioxidative potency on the process of amyloid fibril formation and
      dissociation. Specifically, the hydrophobic and/or aromatic character of the
      compounds makes the major contribution to the anti-formation and anti-extension
      effects, whereas the antioxidative potency relates mostly to the promotion of
      destabilization.

PMID- 17453628
TI  - Severe ataxia with neuropathy in hereditary gelsolin amyloidosis: a case report.
AB  - Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder caused
      by a G654A or G654T gelsolin mutation, reported from Europe, North America, and
      Japan. Principal clinical signs are corneal lattice dystrophy, cutis laxa and
      cranial neuropathy, often deleterious at advanced age. Peripheral neuropathy, if
      present, is usually mild. We report a 78-year-old male Finnish patient who
      presented with ataxia and mainly sensory peripheral polyneuropathy (PNP) signs,
      causing severe disability and ambulation loss. Electrophysiological studies
      showed severe generalized chronic mainly axonal sensorimotor PNP with facial
      paralysis. In magnetic resonance imaging proximal lower limb and axial muscle
      atrophy with fatty degeneration as well as moderate spinal cord atrophy were
      seen. A G654A gelsolin mutation was demonstrated but no other possible causes of
      his disability were found. At age 79 years he became bedridden and died of
      pulmonary embolism. Neuropathological examination revealed marked gelsolin
      amyloid deposition at vascular and connective tissue sites along the entire
      length of the peripheral nerves extending to the spinal nerve roots, associated
      with severe degeneration of nerve fibers and posterior columns. Our report shows
      that advanced AGel amyloidosis due to degeneration of central and distal sensory
      nerve projections results in deleterious ataxia with fatal outcome. Severe
      posterior column atrophy may reflect radicular AGel deposition, although even
      altered gelsolin-actin interactions in neural cells possibly contribute to
      neurodegeneration with successive ataxia in carriers of a G654A gelsolin
      mutation.

PMID- 17453631
TI  - Elevated levels of transcripts encoding a human retroviral envelope protein
      (syncytin) in muscles from patients with motor neuron disease.
AB  - Retroviral components of both exogenous and endogenous origins have been
      associated with nervous system diseases in both animals and humans. In the
      present study, the levels of transcripts from elements in the human endogenous
      retrovirus (HERV) W family were determined in muscle biopsies from patients with
      motor neuron disease (MND) and control subjects. Transcripts from the HERV-W
      element on chromosome 7q21.2 encoding syncytin and from the SOD1 gene were
      detected at elevated levels in biopsies from the most affected muscles from MND
      patients compared to biopsies from control individuals. According to a recent
      study, syncytin is expressed in microglia in normal brain and can be up-regulated
      in macrophages/microglia during inflammation. Although syncytin may have
      cytotoxic effects, it is therefore more likely that the present findings reflect
      a macrophage response in the muscles undergoing neurogenic atrophy than a primary
      pathogenetic event in MND.

PMID- 17453632
TI  - Clinical characteristics of familial amyotrophic lateral sclerosis with a
      Phe20Cys mutation in the SOD1 gene in a Korean family.
AB  - Familial ALS (FALS) is mostly inherited as an age-dependent autosomal dominant
      trait. Since the discovery of mutations in the gene encoding Cu/Zn superoxide
      dismutase (SOD1), testing for SOD1 gene mutations has become a routine part of
      the investigation into ALS patients with a family history. This study reports the
      results of mutation evaluation and clinical features examination in a Korean
      family with ALS. The clinical symptoms, signs and neurological findings of a four
      generation pedigree with 34 members were collected. Five exons of the Cu/Zn SOD
      gene were analyzed by polymerase chain reaction. The clinical signs and symptoms
      of ALS patients began in the lower extremities and spread to the upper
      extremities and bulbar muscles. The mode of transmission was determined to be
      autosomal dominant, and low penetrance was seen in females. The age at onset
      varied from 37 to 77 years. ALSFRS-R testing showed variability in the clinical
      progression of the disease. A point mutation in exon 1 of the SOD1 gene,
      resulting in an amino acid change from phenylalanine 20 to cysteine (F20C), was
      identified. This is the first report of clinical features resulting from the
      Phe20Cys mutation in the SOD1 gene.

PMID- 17453633
TI  - Cerebrospinal fluid from amyotrophic lateral sclerosis patients causes
      fragmentation of the Golgi apparatus in the neonatal rat spinal cord.
AB  - We have previously shown in our laboratory that cerebrospinal fluid from ALS
      patients (ALS-CSF) contains putative toxic factor(s). In the present study we
      determined the effect of ALS-CSF on the integrity of the Golgi apparatus of
      spinal motor neurons in the neonatal rats. CSF was injected intrathecally into
      three-day-old rat pups and subsequently the ultrastructural changes in the motor
      neurons were studied after 48 h, 1, 2 and 3 weeks. We observed that ALS-CSF
      causes fragmentation of the Golgi apparatus in a considerable number of motor
      neurons in the spinal cord. This was further confirmed when motor neurons were
      stained with an antibody against a medial Golgi protein (MG160). Thus, we suggest
      that the putative toxin(s) present in ALS-CSF may cause impairment in the protein
      processing leading to motor neuron death.

PMID- 17453634
TI  - An epigenetic analysis of SOD1 and VEGF in ALS.
AB  - Epigenetic silencing of a gene vital for motor neuron function could underlie
      sporadic ALS. We therefore examined the methylation status of two genes, SOD1 and
      VEGF, which are implicated in ALS. Methylation in the promoters of these genes
      was determined in white cell DNA (10 ALS patients) and brain DNA (six ALS
      patients). The promoter regions were largely unmethylated in all patients.
      Transcriptional silencing of these genes is therefore unlikely to be a common
      mechanism in ALS. However, in view of the potential for treatment of epigenetic
      disorders, promoter methylation in other genes required for motor neuron survival
      needs to be studied.

PMID- 17453635
TI  - Incidence of aspiration pneumonia in ALS in Olmsted County, MN.
AB  - Aspiration pneumonia is believed to be an uncommon complication of amyotrophic
      lateral sclerosis (ALS). However, the incidence of aspiration pneumonia and its
      contribution to morbidity and mortality are unknown in ALS. All cases of ALS from
      Olmsted County, Minnesota from 1990 to 2005 were reviewed. Baseline demographics
      were noted for all cases. Dates of diagnosis, PEG tube placement, death and
      survival status were also noted. All cases of aspiration pneumonia were
      identified. Forty cases of ALS were identified over the 15-year period. The
      incidence rate was 1.7 cases per 100,000 person years. There was an overall mean
      survival of 26 months from diagnosis. Aspiration pneumonia occurred in five (13%)
      cases. There was a mean survival of two months following aspiration pneumonia.
      The strongest risk factor for aspiration pneumonia was nursing home residence
      with a relative risk of 7.1 (p = 0.02) We conclude that the incidence rates and
      demographics of our ALS population have remained stable over time. Aspiration
      pneumonia occurs in a minority but is associated with a high mortality. ALS
      subjects residing in nursing homes are at the greatest risk.

PMID- 17453636
TI  - The Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40): evidence
      for a method of imputing missing data.
AB  - The Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) is the most
      widely validated measure of health status for use with patients diagnosed with
      motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). The questionnaire
      was designed to be used in studies evaluating treatment regimes where missing
      data may cause problems with data analyses. The purpose of this paper is to
      evaluate an algorithm for the imputation of missing dimension scores on the ALSAQ
      40. We used a postal survey of patients diagnosed with MND/ALS. One thousand,
      nine hundred and seventy-nine patients were surveyed and 1093 (55.2%)
      questionnaires returned. Of these, complete ALSAQ-40 data was available in 854
      (85.8%) cases. Data were deleted from this complete dataset, and in a randomly
      selected subset of 100 cases, and then imputed using the Expectation Maximization
      (EM) algorithm: results were then compared to the dataset prior to data deletion.
      Descriptive statistics, mean scores and spread of scores were almost identical
      between original and imputed datasets. Furthermore, the two datasets were highly
      correlated (intra-class correlation coefficient = 0.95 or greater), and mean
      differences were small (+/-1.00). We concluded that EM imputation for the ALSAQ
      40 provides data that closely mirrors the original when this has been
      deliberately removed. Consequently, EM is likely to be appropriate for studies
      using the ALSAQ-40 that contain missing data points.

PMID- 17453637
TI  - Validity of the Dutch version of the Amyotrophic Lateral Sclerosis Assessment
      Questionnaire, ALSAQ-40, ALSAQ-5.
AB  - The objective was to validate the Dutch translation of the 40-item and 5-item
      Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40, ALSAQ-5).
      Eighty-one ALS patients participated in this cross-sectional study. The measures
      used were the ALSAQ-40, the ALSAQ-5, MOS Short-Form-36 (SF-36) and Revised ALS
      Functional Rating Scale (ALSFRS-R). The Dutch ALSAQ-40 was sensitive to
      differences in disease severity (all scales Kruskal-Wallis, p<0.05), had no floor
      and few ceiling effects (Communication, Eating and Drinking scales), had
      excellent internal consistency reliability (all scales Cronbach's alpha >0.90,
      all item to subscale correlations above 0.40) and showed good construct validity
      as it correlated as expected with SF-36 and ALSFRS-R scores. The total and item
      scores of the ALSAQ-5 were strongly correlated with the corresponding total and
      subscale scores of the ALSAQ-40 (Spearman's rho >0.80). The ALSAQ-5 and ALSAQ-40
      showed comparable correlations with the subscales of the SF-36 and the ALSFRS-R,
      except for Activities Daily Living and Independence (ADL). All other results of
      the Dutch ALSAQ-40 and ALSAQ-5 were comparable to those of the original UK
      questionnaires. It is concluded that the psychometric properties of the Dutch
      version of the ALSAQ-40 and the ALSAQ-5 are good and similar to those of the
      original English version.

PMID- 17453638
TI  - Sleep characteristics of amyotrophic lateral sclerosis in patients with preserved
      diaphragmatic function.
AB  - There are a number of sleep studies in amyotrophic lateral sclerosis (ALS), in
      general including a heterogeneous population of patients. We aimed to study sleep
      in a population of selected ALS patients by investigating nocturnal
      polysomnography (PSG) characteristics in ALS patients with normal respiratory
      function tests and preserved diaphragmatic innervation. Ninety-two ALS patients
      were screened by percutaneous nocturnal oximetry (PNO). Eleven ALS patients with
      normal respiratory function tests, phrenic motor responses and preserved motor
      units on needle electromyography of the diaphragm, but abnormal PNO, were
      selected for PSG. REM was present in eight patients, but normal in only three.
      Three patients had mixed apnoea-hypopnoea, severe in one. Seven showed a pattern
      of periodic mild O(2) desaturation, which occurred in REM 3, REM and NREM 3 and
      in NREM sleep 1. One patient studied six months later had more severe changes in
      the second evaluation. In conclusion, the most common sleep disordered breathing
      was periodic mild O(2) desaturation independent of the sleep stage (REM, NREM).
      This might represent central drive dysfunction or respiratory muscle fatigue in
      ALS.

PMID- 17453639
TI  - A comparison of maximal inspiratory pressure and forced vital capacity as
      potential criteria for initiating non-invasive ventilation in amyotrophic lateral
      sclerosis.
AB  - Using a retrospective analysis of 161 patients with amyotrophic lateral sclerosis
      (ALS) from the Western ALS study group (WALS) database, the sensitivity of
      maximal inspiratory pressure (MIP)< -60 cm H(2)O and forced vital capacity (FVC)<
      50% as US Medicare thresholds for initiating non-invasive ventilation (NIV) were
      compared. Sixty-five per cent of patients at enrollment met the MIP criterion,
      compared with only 8% of patients who met the FVC criterion. There were no cases
      in which FVC< 50% antedated MIP< -60 cm H(2)O. The longitudinal data showed that
      patients reached the MIP criterion 4 to 6.5 months earlier than the FVC
      criterion. For patients with clinical signs and symptoms needing treatment with
      NIV, a MIP< -60 cm H(2)O allows US clinicians to obtain non-invasive ventilatory
      support for patients earlier than if using the FVC criterion alone.

PMID- 17453640
TI  - Impaired interhemispheric inhibition in amyotrophic lateral sclerosis.
AB  - The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) remains unknown.
      Neurophysiological studies provide evidence of hyperexcitability of the motor
      cortex or of impairment of inhibitory intrahemispheric modulation of the
      corticomotoneuron in ALS. In this paper, we used TMS to elicit transcallosal
      inhibition of the motor cortex in ALS patients in order to investigate whether
      interhemispheric inhibitory mechanisms subserved by callosal fibres are also
      disturbed in ALS. Twenty-five patients with ALS and 18 controls were recruited
      for the study. Resting Motor Threshold (RMT), Silent Period (SP) and
      interhemispheric inhibition (IHI) were recorded. No significant difference was
      detected regarding RMT or the duration of SP between patients and controls. IHI
      was detected in all controls. IHI was totally absent in eight patients, in
      another eight patients IHI did not reach a significant level and in the remaining
      nine patients was normal. The degree of IHI was significantly lower in ALS
      patients than in controls (p = 0.001). In conclusion, altered IHI in ALS patients
      is in line with the general pattern of reduced corticomotoneuron inhibition,
      being thus, one of the factors which may lead to chronic overexcitation of
      pyramidal cells.

PMID- 17453641
TI  - Clinical highlights. 17th International Symposium on ALS/MND Yokohama, Japan,
      November 30, 2006 through December 2, 2006.

PMID- 17453642
TI  - Scientific highlights. 17th International Symposium on ALS/MND Yokohama, Japan,
      November 30, 2006 through December 2, 2006.

PMID- 17453643
TI  - Efficacy of riluzole: who are the patients enrolled in the studies?

PMID- 17453645
TI  - Motor neuron disease in methamphetamine abusers.

PMID- 17453646
TI  - Mapping of a quantitative trait locus for beef marbling on bovine chromosome 9 in
      purebred Japanese black cattle.
AB  - The goal of this study is to detect quantitative trait loci (QTL) for carcass
      traits applicable for a DNA-based breeding system in a Japanese Black cattle
      population. A purebred paternal half-sib family from a commercial line composed
      of 65 steers was initially analyzed using 188 informative microsatellites giving
      a 16-cM average interval covering 29 autosomes. A significant QTL for marbling
      was detected in the centromeric portion of bovine chromosome (BTA) 9. After
      additional marker genotyping across a larger sample size composed of 169
      individuals, this locus was refined to a 20-cM confidence interval between
      microsatellites BM1227 (24 cM) and DIK2741 (50 cM) at a 1% chromosome-wise
      threshold. The allele substitution effect between Q and q for a beef marbling
      standard score (1 to 12 range) on BTA9 was 1.0 (5.7% of total phenotypic variance
      in QTL contribution in this family). This result provides a primary platform for
      a marker-assisted selection system of the beef marbling trait within the Japanese
      Black (Wagyu) cattle population.

PMID- 17453647
TI  - Genetic diversity and differentiation of dromedarian camel of India.
AB  - Estimation of genetic variability and relationship among different livestock
      breeds is important for management of genetic resources for their sustainable
      utilization and conservation. This is more important when the livestock species,
      like camel, have shown a sharp decline in head count during the last decade. In
      the present study we estimated genetic variability and relationship among four
      camel breeds of India using 23 microsatellite loci. A total of 252 alleles were
      observed across all the four populations with mean number of alleles per locus as
      8.04, 7.30, 6.39, and 7.43 for Bikaneri, Jaisalmeri, Kutchi, and Mewari breeds,
      respectively. The mean observed heterozygosity of the four breeds were 0.58,
      0.57, 0.56, and 0.60 for Bikaneri, Jaisalmeri, Kutchi, and Mewari breeds,
      respectively and were lower than expected heterozygosity values. The mean
      estimates of F statistics were 0.227+/-0.044 (F(IT)), 0.157+/-0.038 (F(IS)), and
      0.082+/-0.019 (F(ST)). The values were significantly different from zero for all
      the three measures and point towards the existence of population structure and
      moderate differentiation in four camel breeds. The exact test also indicated
      significant population differentiation (P < 0.001). The analysis of molecular
      variance revealed 12% of the variation attributed to among populations and 88%
      within populations. Sixty-nine percent of the individuals could be correctly
      assigned using "leave one out" procedure. All the individuals of Mewari and 42
      out of 44 Jaisalmeri were correctly assigned. The existence of strong population
      structure in Jaisalmeri and Mewari camel was further substantiated by Nei's
      standard genetic distance as well as interindividual allele sharing distance.
      Thus these two breeds owing to selection for specific traits are distinct from
      other camel breeds.

PMID- 17453648
TI  - Polymorphism of heart fatty acid-binding protein gene associatied with fatness
      traits in the chicken.
AB  - Fatty acid-binding proteins (FABP) belong to a superfamily of lipid binding
      proteins that exhibit a high affinity for long chain fatty acids and appear to
      function in metabolism and intracellular transportation of lipids. The current
      study was designed to investigate the effects of heart (H)-FABP gene on chicken
      growth and body composition traits. The Northeast Agricultural University
      divergent broiler lines for abdominal fat and a broiler X silkie F2 population
      were used in this study. Body weight and body composition traits were measured in
      the populations. Primers were designed according to the chicken H-FABP gene
      sequence. Polymorphisms between parental lines were detected by DNA sequencing.
      PCR-RFLP and PCR-fragment length polymorphism methods were developed to genotype
      the populations. The results showed that the H-FABP gene polymorphisms in the two
      populations were associated with abdominal fat percentage. It implied that H-FABP
      gene can be a candidate locus or linked to a major gene(s) that affects abdominal
      fat content in the chicken.

PMID- 17453649
TI  - Characterization of porcine EPLIN gene revealed distinct expression patterns for
      the two isoforms.
AB  - Epithelial protein lost in neoplasm (EPLIN) is a cytoskeleton-associated protein
      that is down-regulated in transformed cells. Two EPLIN isoforms (alpha and beta)
      are generated by alternative promoter usage from a single gene. In pigs EPLIN was
      preferentially expressed in the muscle of splay-legged piglets, but not in the
      healthy ones, suggesting that it plays an important role in muscle development. A
      precise mRNA expression analysis through muscle development could shed some light
      on the EPLIN function associated with splayed legs. This article describes the
      isolation of the two alternative splice variants of EPLIN mRNA in pigs. The
      chromosome assignment and several polymorphism sites were also identified to lay
      a foundation for potential breeding applications. Gene expression analysis by
      real-time polymerase chain reaction (PCR) showed that both of transcripts were
      expressed in almost all tissues examined but in variable amounts in adult pigs.
      The temporal expression analysis indicated that they are not coexpressional
      through muscle development: EPLIN-alpha was detected in developing skeletal
      muscle, but EPLIN-beta was not.

PMID- 17453650
TI  - SNaPshot minisequencing and a panel of candidate genes for complex routine
      testing of meat performance traits in pigs.
AB  - The aim of the study was to introduce a convenient method for identification of
      differences among individual animals in genes supposed to influence meat
      performance in pigs. The set of seven candidate genes (IGF2, FOS, MC4R, DGAT1,
      MYF4, MYF, and MC3R) was used. To determine the genotypes, multiplex polymerase
      chain reaction (PCR) and minisequencing using SNaPshot system (Applied
      Biosystems; Forster City, CA, USA) were applied. The efficiency of this gene
      panel for routine testing in pigs was verified in the Black Pied Prestice pig
      breed by the statistical general linear model. The results showed that both the
      method and the gene panel are convenient for meat quality testing and offer
      reproducible results.

PMID- 17453651
TI  - Nucleotide sequence and polymorphism of the pig acyl coenzyme A synthetase long
      chain 1 (ACSL1) gene.
AB  - We have sequenced 3,013 bp of the pig acyl coenzyme A long-chain synthetase 1
      (ACSL1) gene. Sequence analysis allowed us to identify three conserved elements
      in the predicted amino acid sequence, two of them related to the ATP/AMP
      signature motif and the third involved in enzyme catalysis and fatty acid
      substrate specificity. In addition, we have identified five C --> T and one G -->
      A transition polymorphisms located in exon 16 (SNPe16), exon 17 (SNPe17) and the
      3' UTR (SNPa to d), which have been genotyped in 143 pigs from the Landrace,
      Large White, Pietrain, Iberian, and Duroc breeds.

PMID- 17453652
TI  - Isolation and sequence characterization of mammary derived growth inhibitor gene
      of riverine buffalo (Bubalus bubalis).
AB  - In this study, attempts have been made to identify and characterize water buffalo
      (Bubalus bubalis) mammary derived growth inhibitor (MDGI) gene, isolated from a
      mammary gland cDNA library of lactating buffalo. The complete MDGI cDNA was of
      698 nucleotides, consisting 61 nucleotides in 5' UTR, coding region of 402
      nucleotides, and 235 nucleotides representing the 3' UTR. Comparison of
      nucleotide and deduced amino acid sequence data with that of MDGI/fatty acid
      binding protein (FABP) of other species shows three buffalo specific nucleotide
      changes while seven nucleotide changes were common to cattle and buffalo. Buffalo
      and cattle MDGI had 100% amino acid sequence similarity, which also shared three
      amino acid changes: 34 (Ala-Gly), 109 (Leu-Met), and 132 (Glu-Gln) as compared to
      other species. Comparison with FABPs reported from other cattle tissues revealed
      highest amino acid sequence similarity with FABP-heart (100%) and least with FABP
      liver (20.5%). Phylogenetic analysis revealed cattle MDGI to be closest to
      buffalo, while mouse MDGI was distantly placed, whereas different tissue derived
      FABPs of cattle showed FABP-heart closest and FABP-epidermis most distantly
      placed from buffalo MDGI. This report also differs from the earlier findings that
      MDGI is intermediate of FABP-heart and adipose.

PMID- 17453653
TI  - Effect of different parthenogenetic activation methods on the developmental
      competence of in vitro matured porcine oocytes.
AB  - The aim of this study was to investigate the effect of electrical pulse, ethanol,
      and ionomycin combined with cycloheximide (CHX), cytochalasin B (CB), and 6
      dimethylaminopurine (6-DMAP) on parthenogenetic developmental competence of in
      vitro matured porcine oocytes. In experiment 1, oocytes were treated with direct
      current electrical pulse (DC pulse) and then incubated in the NCSU-23 medium
      supplemented with CHX, 6-DMAP, CB + CHX, and CB + 6-DMAP for 6 h, respectively.
      The rate of blastocyst development in DC pulse + CB + 6-DMAP group was
      significantly higher than those in other groups (42.4% vs 23.9% approximately
      35.8%; P < 0.05); however, there were no differences in both of the cleavage rate
      and the cell number of blastocysts among four groups. In experiment 2, oocytes
      were treated with NCSU-23 medium containing 20 muM ionomycin for 40 min and then
      incubated in the NCSU-23 medium supplemented with CHX, 6-DMAP, CB + CHX and CB +
      6-DMAP for 6 h, respectively. The rates of cleavage and blastocyst development in
      ionomycin + 6-DMAP group were higher than those obtained in other groups (66.2%
      vs 46.3% approximately 57.3%; 22.3% vs 7.4% approximately 16.1%; P < 0.05). In
      experiment 3, the activation effects of ethanol combined with 6-DMAP, CHX, CB + 6
      DMAP and CB + CHX were investigated. The rates of cleavage and blastocyst
      development in ethanol + CB + 6-DMAP group were significantly higher than those
      in other groups (55.5% vs 42% approximately 46.2%; 18.0% vs 7.1% approximately
      11.9%; P < 0.05). In experiment 4, the optimal activation protocols in each group
      plus DC pulse + ionomycin + 6-DMAP were compared. The results showed the rates of
      cleavage in DC pulse + CB + 6-DMAP group and ionomycin + 6-DMAP were higher than
      those in ethanol + CB + 6-DMAP and DC pulse + ionomycin + 6-DMAP (73.8-74.4% vs
      56.5-57.5%; P < 0.05), but the blastocyst development only in DC pulse + CB + 6
      DMAP group was significantly higher than that in other groups (34.1% vs 13.4%
      approximately 22.3%; P < 0.05). Total cell number of blastocysts in the group of
      DC pulse + ionomycin + 6-DMAP was higher than that in other groups (34.1 vs 25.3
      27.2; P < 0.05). In conclusion, DC pulse, ethanol, CB, and 6-DMAP all affected
      the parthenogenesis of porcine oocytes matured in vitro, but their combination of
      DC pulse + CB + 6-DMAP showed the best result in both of cleavage and blastocyst
      development.

PMID- 17453654
TI  - Relapse during continuation pharmacotherapy after acute response to ECT: a
      comparison of usual care versus protocolized treatment.
AB  - BACKGROUND: ECT, an effective treatment for major depression, is associated with
      a high relapse rate. Roughly half of all responders during the acute treatment
      phase relapse during continuation treatment. Recent literature has pointed out an
      "efficacy-effectiveness gap" in outcomes of patients enrolled in study protocols
      when compared to "care as usual." This study compares the effectiveness of usual
      care versus protocolized pharmacotherapy in preventing relapse following ECT.
      METHODS: One hundred twenty-six depressed patients responded to acute ECT.
      Seventy-three were randomized to continuation pharmacotherapy consisting of
      nortriptyline, nortriptyline-plus-lithium, or placebo. The 53 patients that
      refused to participate in the randomized trial were followed naturalistically for
      6 months or until depression relapse in usual care settings. RESULTS: All but one
      "usual care" patient received pharmacotherapy following ECT; 27 (51%) relapsed
      within 6 months. Only one usual care patient received continuation ECT as a first
      line treatment. The "usual care" relapse rate was intermediate to the relapse
      rates of the patients receiving protocolized nortriptyline (60%) and
      nortriptyline-plus-lithium (39%), but superior to placebo (84%). CONCLUSIONS: The
      relapse rate associated with usual care following ECT was comparable to that of
      protocolized pharmacotherapy. This suggests that high relapse rates following ECT
      are not due solely to an "efficacy-effectiveness gap."

PMID- 17453655
TI  - Hopelessness as a predictor of non-response to fluoxetine in major depressive
      disorder.
AB  - BACKGROUND: The purpose of this study was to study hopelessness as a predictor of
      response to fluoxetine in outpatients with Major Depressive Disorder (MDD).
      METHODS: The degree of hopelessness was assessed during the baseline visit with
      the use of the Beck Hopelessness Scale (BHS) in 312 patients with MDD (56.1%
      women; 39.8 +/- 10.3 years of age) who entered an 8-week, 20-mg, fixed-dose, open
      trial of fluoxetine. With the use of a logistic regression we tested whether BHS
      scores at baseline predicted clinical response, controlling for the severity of
      depression as reflected by the total score on the 17-item Hamilton Depression
      Rating Scale (HAM-D-17). With the use of a multiple regression we also tested
      whether BHS scores at baseline predicted HAM-D-17 scores at endpoint, controlling
      for HAM-D-17 scores at baseline. RESULTS: After controlling for depression
      severity at baseline, a greater degree of hopelessness was found to significantly
      increase the risk of non-response to fluoxetine (p = 0.0413), as well as the risk
      of greater endpoint depression severity (p = 0.0305). CONCLUSIONS: Hopelessness
      appeared to be associated with poorer response to treatment with fluoxetine in
      MDD, and this was independent of depression severity. Similar studies involving
      treatment with higher doses of fluoxetine and for greater duration as well as a
      placebo comparator arm are needed to further explore the relationship between
      hopelessness, placebo response and drug response.

PMID- 17453656
TI  - Catatonic variants, hyperthermic extrapyramidal reactions, and subtypes of
      neuroleptic malignant syndrome.
AB  - BACKGROUND: This case series study examines the hypothesis that neuroleptic
      malignant syndrome (NMS) is a heterogeneous condition including catatonic
      variants and non-catatonic pathological reactions to antipsychotics. METHODS:
      Fourteen episodes of NMS were prospectively identified. Patients were examined
      for catatonia during the course of NMS. Close monitoring of catatonia episodes
      and suspected cases of evolving NMS for possible NMS development provided data on
      the pre-NMS clinical course. All NMS episodes received benzodiazepines. Episodes
      with catatonia diagnosed were compared with those without catatonia, noting their
      presentation, clinical course and responses to treatment. RESULTS: Concurrent
      catatonia was diagnosed in 9 episodes. In 6 of them antecedent catatonia
      progressed to NMS following antipsychotic exposure (NMS of antipsychotic
      converted catatonia). In 3 episodes, a parkinsonian-catatonic syndrome with fever
      and autonomic abnormality developed in reaction to antipsychotics (NMS of
      antipsychotic-induced catatonia). Catatonia was not diagnosed in 5 during the
      longitudinal course of NMS. A severe extrapyramidal reaction to antipsychotics
      with associated delirium preceded all 5 episodes. Seven of the 9 NMS episodes
      with catatonia and none of the 5 without catatonia showed significant responses
      to benzodiazepines. CONCLUSIONS: The preliminary findings support the hypothesis
      that NMS is a heterogeneous condition including catatonic variants and non
      catatonic hyperthermic extrapyramidal reactions to antipsychotics, differing in
      presentation, clinical course, and treatment responses.

PMID- 17453657
TI  - A Comparison of adults with antisocial personality traits with and without
      childhood conduct disorder.
AB  - BACKGROUND: Antisocial personality disorder (ASPD) in DSM-IV is unique among
      personality disorder diagnoses in requiring the individual to satisfy a number of
      childhood criteria in addition to relevant traits exhibited in adulthood. We
      examined the validity of this childhood requirement. METHODS: Personality
      disordered individuals assessed using the International Personality Disorder
      Examination and exhibiting a sufficient number of adult antisocial traits to meet
      criterion A of DSM-IV were subdivided into those who exhibited antisocial traits
      in both adulthood and childhood and those who had such traits in adulthood only.
      The two groups were then compared on a number of historical, clinical, and self
      report measures. RESULTS: Thirty individuals meeting both childhood and adult
      criteria (ASPD) were compared with 39 meeting adult antisocial criteria only
      (ASS). Few differences were found between the two groups on the measures
      examined, although those in the ASPD group appeared more severe and had higher
      anger scores on the STAXI-2 psychometric test. CONCLUSIONS: This failure to find
      clinically important differences between the two groups is in agreement with
      previous reports and needs to be taken into account in future revisions of ASPD
      in DSM.

PMID- 17453658
TI  - An open-label study to evaluate switching from an SSRI or SNRI to tiagabine to
      alleviate antidepressant-induced sexual dysfunction in generalized anxiety
      disorder.
AB  - BACKGROUND: This study investigated tiagabine monotherapy in subjects with
      generalized anxiety disorder (GAD) who had been switched from selective serotonin
      reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors
      (SNRIs) as a result of antidepressant-induced sexual dysfunction. METHODS: Adults
      with DSM-IV GAD, an adequate therapeutic response (> or =50% decrease in Hamilton
      Rating Scale for Anxiety [HAM-A] total score) to SSRI or SNRI and sexual
      dysfunction were switched to open-label tiagabine 4-12 mg/day for 14 weeks.
      Assessments included the HAM-A, Hospital Anxiety & Depression Scale (HADS) and
      the Arizona Sexual Experiences Scale (ASEX); assessments were made at baseline
      and at Weeks 4, 8, and 14. RESULTS: Twenty six subjects were included in the
      analysis. Tiagabine showed no worsening in baseline symptoms of GAD, with non
      significant changes from baseline in mean HAM-A total scores and HADS Anxiety and
      Depression subscale scores. There was a significant (p < 0.001) reduction in ASEX
      total scores from baseline following tiagabine, indicating an alleviation of
      sexual dysfunction. Tiagabine was reasonably tolerated; the most commonly
      reported adverse events were dizziness/light headedness (n = 6; 23%), nausea (n =
      6; 23%) and fatigue (n = 2; 8%). CONCLUSIONS: Tiagabine may be useful in subjects
      who respond to previous antidepressant therapy but develop sexual dysfunction as
      an adverse event.

PMID- 17453659
TI  - Suicide risk and symptom reduction in patients assigned to placebo in duloxetine
      and escitalopram clinical trials: analysis of the FDA summary basis of approval
      reports.
AB  - BACKGROUND: We assessed suicide and suicide attempt risk as well as symptom
      reduction among 3,282 depressed patients participating in duloxetine and
      escitalopram clinical trials assigned to either an antidepressant or placebo.
      METHODS: We reviewed the FDA Summary Basis of Approval reports for data regarding
      safety and efficacy for duloxetine and escitalopram. Furthermore, we compared
      suicide risk among antidepressant clinical trials in this study with our two
      previous analyses on seven antidepressant clinical trials. RESULTS: Suicide and
      suicide attempt risk varied considerably among the three analyses, showing up to
      ten fold differences. Interestingly, the variability exists across the three
      reports, rather than between treatments (antidepressants versus placebo).
      CONCLUSIONS: These findings suggest caution in generalizing suicide risk even
      from a relatively large number of participants and thus, firm conclusions can
      only be drawn if the number of participants is overwhelmingly large
      (approximately two million patients). We also noted similar magnitude of response
      to placebo and antidepressants among the three studies.

PMID- 17453660
TI  - State and trait in personality disorders.
AB  - BACKGROUND: The current definitions of personality disorder indicate early onset,
      long duration and disorders of relatively stable severity. It has been noticed by
      a number of authors and researchers that at times personality pathology can be
      quite variable and not fit that model. METHODS: This report examines the
      possibility that there is a valid psychiatric disorder whose key feature is
      episodic personality dysfunction. The disorder would be designated State
      personality disorder (State PD) to separate it from Trait personality disorder
      (Trait PD), which is the non episodic form, and from no personality disorder (No
      PD). This report examines what criteria might be necessary to validate such a
      diagnosis. RESULTS: It finds that State personality disorder has been identified
      in two distinct populations and in both it can be distinguished from its near
      neighbor disorders of Trait PD and No PD. The family history method of
      personality clusters distinguishes State PD from its near neighbors and provides
      a possible biological marker for the disorder. In two separate populations the
      disorder is related to an independent measure of the hypothesized underlying
      personality construct. Although the two populations in which the phenomenon has
      been clinically identified are very different and cannot be directly compared, in
      both it appears that clinical variables may distinguish State PD from its near
      neighbor diagnoses. State PD appears to have a negative relationship to suicidal
      ideation and might affect the course of treatment of comorbid Axis I disorders.
      CONCLUSIONS: It is concluded that State PD represents a valid diagnostic entity.

PMID- 17453661
TI  - MDMA (Ecstasy).
AB  - BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA or Ecstasy) is a synthetic
      amphetamine analogue that is recreationally used to obtain a psychological effect
      of enhanced affiliative emotional response. Its use in Western countries appears
      to be increasing, particularly among young individuals. METHODS: Pertinent basic
      and clinical literature is critically reviewed. RESULTS: A significant body of
      literature suggests that the patterns of MDMA use differ from traditional drugs
      of abuse, with relatively uncommon dependence and escalation of dosage.
      Nonetheless, MDMA is also neurotoxic with significant deleterious effects on
      serotonergic neurons, memory, and mood. Despite this, there is a dearth of
      treatment strategies for both acute intoxication and consequences of longer term
      use. CONCLUSIONS: MDMA is an important drug of abuse that has a wide range of
      adverse consequences.

PMID- 17453662
TI  - Polysomnography in sleep maintenance insomnia patients.

PMID- 17453672
TI  - Endothelial progenitor cells in health and atherosclerotic disease.
AB  - Cardiovascular disease is associated with damage of the endothelial monolayer
      leading to endothelial dysfunction and atherosclerosis. A growing body of
      evidence suggests that circulating endothelial progenitor cells play an important
      role in endothelial cell regeneration. In this review we discuss the evolving
      role of stem- and progenitor cells in the maintenance of the vascular wall
      focusing on new pathophysiological concepts of endothelial cell regeneration. We
      discuss new insights into vascular stem cell biology derived from experimental
      and clinical studies.

PMID- 17453673
TI  - Genetics of dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is a myocardial disease characterized by dilatation
      and impaired systolic function of the left or both ventricles. The etiology of
      DCM is multifactorial, and many different clinical conditions can lead to the
      phenotype of DCM. During recent years it has become evident that genetic factors
      play an important role in the etiology and pathogenesis of idiopathic DCM. The
      genetics of DCM have been under intensive investigation lately, and thereby the
      knowledge on the genetic basis of DCM has increased rapidly. The genetic
      background of the disease seems to be relatively heterogeneous, and the disease
      associated mutations concern mostly single families and only few affected
      patients. Disease-associated mutations have been detected e.g. in genes encoding
      sarcomere, cytoskeletal, and nuclear proteins, as well as proteins involved with
      regulation of Ca(2+) metabolism. The mechanisms, by which mutations eventually
      result in clinical heart failure, are complex and not yet totally resolved. DCM
      causes considerable morbidity and mortality. Better knowledge of the genetic
      background and disease-causing mechanisms would probably help us in focusing
      early treatment on right subjects and potentially also developing new treatment
      modalities and improving cardiac outcome in the affected patients. This review
      deals with DCM of genetic origin.

PMID- 17453674
TI  - Cutaneous gene therapy.
AB  - Possibilities of using the skin for somatic gene therapy have been investigated
      for more than 20 years. Strategies have included both direct gene transfer into
      the skin and indirect gene transfer utilizing cultured cells as an intermediate
      step for gene manipulation. Viral as well as nonviral vectors have been used, and
      both gene addition and gene editing have been performed. Although cutaneous gene
      therapy has now begun translating into clinical medicine (as seen by the first
      clinical gene therapy project of an inherited skin disorder) further developments
      are still required.

PMID- 17453675
TI  - Ghrelin, the peripheral hunger hormone.
AB  - In the current review we summarize the available data concerning the gastric
      hormone ghrelin and its receptor. Ghrelin stimulates short-term food intake and
      long-term body weight regulation via its adipogenic and diabetogenic effects.
      Ghrelin stimulates gastric emptying, and these effects could be explored from a
      therapeutic point of view. Ghrelin levels change profoundly in anorexia, in
      states of insulin resistance, in obesity, and after bariatric surgery, suggesting
      that this is an important hormone in body weight regulation.

PMID- 17453676
TI  - Insulin resistance as predictor of the angiographic severity and extent of
      coronary artery disease.
AB  - BACKGROUND: Insulin resistance (IR) is frequently observed in patients with
      coronary artery disease (CAD). Aim. To examine the association between IR and
      severity and extent of CAD. METHODS: Quantitative coronary angiography (QCA) was
      used to assess coronary atherosclerosis in 107 patients with clinically suspected
      CAD. QCA-derived indexes reflecting CAD severity, extent, and overall atheroma
      burden were calculated for the entire coronary tree, and separately for different
      coronary segments. IR was quantified using the homeostasis model assessment
      insulin resistance index (HOMA IR). Nondiabetic subjects (n = 83) were divided
      into group 1 (n = 41) with HOMA IR <1.8 (the median value), and group 2 (n = 42)
      with HOMA IR >or=1.8. Group 3 comprised diabetic subjects (n = 24). RESULTS:
      Global age- and gender-adjusted indexes for severity (P = 0.007), extent (P =
      0.038), and atheroma burden (P = 0.035) of CAD were higher in group 2 than in
      group 1. Similarly, the global severity (P = 0.027), extent (P = 0.090), and
      global atheroma burden (P = 0.024) indexes were higher in group 3 compared with
      group 1. IR was correlated with quantitative angiographic indexes for distal
      segments only, but not for proximal or mid segments of coronary vessels.
      CONCLUSIONS: Patients with more severe degree of IR have a more severe,
      extensive, and distal type of CAD than patients with lower degree of IR.

PMID- 17453677
TI  - Are exposure to cytomegalovirus and genetic variation on chromosome 6p joint risk
      factors for schizophrenia?
AB  - BACKGROUND: Published data support genetic variants, as well as certain
      infectious agents, as potential risk factors for schizophrenia. Less is known
      about interactions between the risk factors. AIM: To evaluate exposure to
      infectious agents and host genetic variation as joint risk factors. METHODS: We
      investigated four infectious agents: cytomegalovirus (CMV), herpes simplex
      viruses 1 and 2 (HSV1, HSV2), and Toxoplasma gondii (TOX). We initially compared
      exposure using specific serum antibodies, among simplex and multiplex nuclear
      families (one or more than one affected offspring, respectively). If interactions
      between infectious agents and host genetic variation are important risk factors
      for schizophrenia, we reasoned that they would be more prominent among multiplex
      versus simplex families. We also evaluated the role of variation at chromosome
      6p21-p23 in conjunction with exposure. We used 22 short tandem repeat
      polymorphisms (STRPs) dispersed across this region. RESULTS: Though exposure to
      all four agents was increased among multiplex families versus simplex families,
      the difference was consistently significant only for CMV (odds of exposure to CMV
      in multiplex families: 2.47, 95% CI: 1.48-5.33). Transmission disequilibrium
      tests and case-control comparisons using STRPs revealed significant
      linkage/association with D6S2672 among CMV+ schizophrenia patients. CONCLUSIONS:
      Polymorphisms near D6S2672 could confer risk for schizophrenia in conjunction
      with CMV exposure.

PMID- 17453678
TI  - Patients with Behcet's disease carry a higher risk for microvascular involvement
      in active disease period.
AB  - BACKGROUND: Behcet's disease (BD) is characterized with remissions and
      exacerbations. However, to date, there is no study to investigate a possible
      association of disease activity (active versus inactive disease period) with
      cardiovascular complications. METHODS: Forty patients with BD were evaluated in
      both active and in inactive disease period. For the control group 45 healthy
      volunteers, age and sex matched, were registered. Subjects with at least a 15-day
      lesion-free period were regarded in inactive disease period, and subjects with
      any oral, skin, and/or genital lesion was regarded as in active disease period.
      In each subject coronary diastolic peak flow velocities (DPFV) were measured at
      baseline and after dipyridamole infusion (0.84 mg/kg over 6 minutes) using an
      Acuson Sequoia C256 echocardiography system. Coronary flow reserve (CFR) was
      defined as the ratio of hyperemic to baseline DPFV. RESULTS: CFR values were
      significantly lower in BD patients compared to the controls (2.57+/-0.50 versus
      2.87+/-0.53, P = 0.006). In active disease period, basal DPFV (24.6+/-7.5 versus
      27.3+/-6.6, P = 0.019) was significantly higher than in the inactive disease
      period. In the active disease period hyperemic DPFV (61.7+/-14.9 versus 56.8+/
      16.7, P = 0.015) values decreased significantly. Therefore, in the active disease
      period CFR significantly decreased from 2.57+/-0.50 to 2.09+/-0.46, P<0.001. The
      only independent predictor of CFR within the active disease period was the
      disease duration (beta = -0.384, P = 0.012). CONCLUSION: Within the active
      disease period, coronary microvascular function is more prominently impaired in
      BD patients. Therefore, BD patients are possibly more vulnerable to
      cardiovascular manifestations when they are in an active disease period.

PMID- 17453679
TI  - Increased inflammatory factors activity in model rats with experimental
      autoimmune prostatitis.
AB  - Male rats were immunized with prostate tissue homogenate supernate (PTHS) of male
      rats with complete Freund's adjuvant (CFA) intra dermal in the multiple points
      and simultaneously immunized with 0.5 ml Pertussis-Diphtheria-Tetanus (PDT)
      vaccine intra peritonea on 0 and 30th day. At the 45th day after first
      immunization, animals were sacrificed and a series of examinations such as HE
      stain, assay of TNF-alpha by ELISA and assay of inducible nitric oxide synthase
      (iNOS) mRNA by in-situ hybridization (ISH) were taken. We observed that there was
      a remarkable up-regulation of TNF-alpha expression in the high dosage model
      group. The results of macropathology, histopathology and iNOS ISH also revealed
      the same tendency. This experimental procedure is effective to induce chronic
      abacterial prostatitis (CAP).

PMID- 17453680
TI  - Effect of sample collection site on semen parameters of healthy young volunteers.
AB  - The effect of sample collection site on semen parameters in ten men aged between
      22 and 24 years was investigated. Sperm was collected at two sites: in a
      university hospital restroom for general use and in a one-person hospital room.
      Samples were collected from the same individual twice, with an interval of two
      weeks between collections. Semen parameters for the two sites were compared.
      Samples were collected after a minimum of three days and not longer than seven
      days of sexual abstinence. Sperm concentration did not differ significantly
      between the university hospital restroom location (86.8 +/- 25.4 x 10(6)/ml; mean
      +/- standard deviation) and the private hospital room (97.1 +/- 72.0 x 10(6)/ml).
      There was no difference in the total motile sperm count or daily sperm production
      between the collection sites. These results suggest that the collection site has
      little effect on semen parameters.

PMID- 17453681
TI  - Urethral cystoscopic realignment and early end-to-end anastomosis develop
      different influence on erectile function in patients with ruptured bulbous
      urethra.
AB  - The objective of this study is to compare the influence on erectile function
      between urethral cystoscopic realignment and early end-to-end anastomosis
      treating ruptured bulbous urethra. 58 cases were selected, 32 had urethral
      cystoscopic realignment (group I) and 26 cases had urethral end-to-end
      anastomosis (group II). The parameters of P-CDU (Penile Color Duplex Ultrasound),
      NPT (Nocturnal Penile Tumescence), and IIEF-5 (International Index of Erectile
      Function) were compared between the two groups 6 months after operation. Group I
      was higher than group II in IIEF (21 vs 14) with significant differences. With P
      CDU we observed an improvement in penile vascularization in group I as confirmed
      by the detection of an increase in peak systolic velocity (PSV) (26 cm/s vs 16
      cm/s, p<0.01) and a decrease in end diastolic velocity (EDV) (3 cm/s vs 6 cm/s
      p<0.05), resulting in an increase in resistive index (RI) (0.85 vs 0.56, p<0.05).
      The parameters of NPT showed a significant increase compared to group II (p<0.01)
      in satisfactory erection number (5 vs 1.5), maximum rigidity (80% vs 42%), and
      total time that the increase in circumference was greater than 30% of baseline
      during sleep (100 sec vs 30 sec). Urethral cystoscopic realignment treating
      ruptured bulbous urethra can reduce the incidence of erectile dysfunction [ED]. A
      long term follow-up should be studied.

PMID- 17453682
TI  - Testicular sperm extraction and ICSI in patients with post-chemotherapy non
      obstructive azoospermia.
AB  - 146 MD-TESE procedures were performed in 74 patients presenting with non
      obstructive azoospermia (NOA). Five of the 74 patients displayed a history of
      chemotherapy. Etiology of chemotherapies included testicular cancer,
      osteosarcoma, Ewing sarcoma, and malignant lymphoma of the stomach. Post
      chemotherapy duration was 2.5-18 years. All patients underwent MD-TESE using
      local anesthesia with spermatic block and sedation. Extracted sperm was
      cryopreserved for ICSI. Histopathologic examination revealed Sertoli cell-only
      syndrome in all five patients; however, sperm were retrieved in 3 subjects. Post
      chemotherapy MD-TESE and ICSI can be applied successfully in some patients with
      NOA. However, freezing semen prior to chemotherapy is recommended.

PMID- 17453683
TI  - Development and retest reliability of a German version of the Sexual Behaviour
      Questionnaire (SBQ-G).
AB  - A German version of the Sexual Behaviour Questionnaire (SBQ-G) is a short self
      rating instrument covering the four domains of sexual function using colloquial
      words. Frequency of sexual dysfunction was counted and chance-corrected retest
      reliability was calculated. Eleven women and 12 men participated. Reception of
      the SBQ-G was favourable and more females than males reported at least moderate
      sexual dysfunction. Sexual arousal and ability to enjoy sex showed the lowest
      retest stability. The SBQ-G is a recommendable clinical instrument with high
      practicability and satisfactory retest reliability. However, gender differences
      and a high variability of sexual functioning in healthy subjects should be kept
      in mind.

PMID- 17453684
TI  - Investigation of DAZ and RBMY1 gene expression in human testis by quantitative
      real-time PCR.
AB  - This study developed quantitative real-time PCR assays for the DAZ and RBMY1
      genes to determine the copy number of RNA extracted from testicular biopsies from
      a cohort of normospermic controls (n=6) and azoospermic males (n=17) including
      two males with Y-chromosome microdeletions (AZFc and AZFb + c). All patients
      underwent testicular sperm extraction (TESE) for intracytoplasmic sperm injection
      (ICSI). Forty percent of the azoospermic cohort showed a significant reduction in
      the copies of at least one of the genes (DAZ P=0.003; RBMY1 P=0.009). The
      histopathology of these patients ranged from Sertoli cell only (SCO) to severe
      hypospermatogenesis with interstitial fibrosis. The patient with the AZFb + c
      deletion lacked expression of DAZ and RBMY1 and had a histopathology of SCO. The
      patient with the AZFc deletion had reduced expression of RBMY1 and no DAZ
      expression with a histopathology of spermatocyte arrest. The quantitative real
      time PCR assays for DAZ and RBMY1 gave positive predictive values of 78% and 70%,
      respectively for the recovery of sperm from testicular biopsy.

PMID- 17453685
TI  - Regulation of steroidogenesis by Cordyceps sinensis mycelium extracted fractions
      with (hCG) treatment in mouse Leydig cells.
AB  - The in vitro effect of extracted fractions of Cordyceps sinensis (CS) mycelium on
      hCG-treated testosterone production from purified normal mouse Leydig cells was
      examined. Different fractions extracted from CS (F1-water soluble polysaccharide,
      F2- water soluble protein and F3- poorly water soluble polysaccharide, and
      protein) were added to Leydig cells with hCG, and the production of testosterone
      was determined by radioimmunoassay (RIA). Testosterone productions stimulated by
      hCG in mouse Leydig cells were suppressed by F2 at 10 mg/ml and F3 at doses from
      3 to 10 mg/ml, respectively. F2 and F3 at 10 mg/ml did inhibit dbcAMP-stimulated
      testosterone productions which indicated that F2 and F3 might affect
      steroidogenesis at the site after the formation of cyclic AMP. Finally,
      cycloheximide inhibited F2- and F3-treated mouse Leydig cell testosterone
      production.

PMID- 17453686
TI  - Effects of testosterone on leptin production in anterior pituitary cells of rats:
      an immunohistochemical study.
AB  - The aim of this study was to immunohistochemically examine the effects of
      orchidectomy and administration of testosterone hormone on leptin production in
      the rat anterior pituitary. Twenty-one male Wistar rats were divided into three
      groups. Group I and group II were designated as control (sham-orchidectomized)
      and orchidectomized rats, respectively. Rats in group III were orchidectomized
      and injected daily with testosterone propionate for 1 month. At the end of the
      experimental period, all animals were sacrificed by decapitation. The pituitary
      glands of all rats were removed and processed for semi-quantitative evaluation of
      immunohistochemical leptin staining. Intensity of immunostaining was determined
      on a scale between 0 (no staining) and 5 (heavy staining). Immunostaining of
      leptin was moderate (3+) in control rats, heavy (5+) in orchidectomized rats, and
      low (1+) in testosterone-treated orchidectomized rats, respectively. These
      findings indicate that orchidectomy increases leptin secretion in anterior
      pituitary cells, and this increase of leptin synthesis can be prevented by
      administration of testosterone propionate. Thus, testosterone seems to affect
      leptin production in the anterior pituitary of male rats.

PMID- 17453687
TI  - Expression of estrogen and androgen receptors in children with hypospadias:
      preliminary report.
AB  - This investigation was conducted to evaluate the presence of estrogen and
      androgen receptors in penile tissues of patients with hypospadias. The biopsy
      specimens from prepuce, glans, and urethral plate were sampled during the
      hypospadias surgery in five patients and were analyzed immunohistochemically.
      Twelve specimens were investigated for the presence of estrogen or androgen
      receptors (n: 24); the result was negative in 9 (37%) and positive in 15 (63%).
      Estrogen receptors were present in 10 specimens (42%) (prepuce: 5, glans: 3, and
      urethral plate: 2). Androgen receptors were present in 5 specimens (21%)
      (prepuce: 3, glans: 1, and urethral plate: 1). There was expression of both
      estrogen and androgen receptors in 5 specimens and only estrogen receptors in the
      remaining 5. Dominant expression of estrogen receptors in penile tissues of
      children with hypospadias may be the postnatal finding of disrupted estrogen and
      androgen receptor interaction during the intrauterine development of external
      genitalia.

PMID- 17453688
TI  - Endocrine response to a single injection of goserelin 3.6 mg or leuprolide 3.75
      mg in men with prostate cancer.
AB  - Hormonal responses were assessed in men with prostate cancer (T2-4, Nx, Mx) who
      were randomized to receive either a single injection of goserelin 3.6 mg or
      leuprolide 3.75 mg. Testosterone increased over the first week, with a
      significantly higher mean rate of change of total testosterone (day 3) and free
      testosterone (days 3 and 7) with leuprolide. Following the initial rise in
      luteinizing hormone (LH), the rate of decrease in LH levels was significantly
      greater with goserelin by day 28. There are significant differences in endocrine
      response to goserelin and leuprolide in the 4 weeks following administration.

PMID- 17453689
TI  - Gossypol with methyltestosterone and ethinylestradiol male does not affect rat
      spermatogonial stem cell differentiation.
AB  - The purpose of this study was to investigate whether administration of the
      regimen of gossypol at 12 mg/kg/day combined with methyltestosterone at 20
      mg/kg/day and ethinylestradiol at 100 microg/kg/day for a long term of twenty
      four weeks could affect the existence and differentiation of rat spermatogonial
      stem cell. This was assessed by conducting TdT-mediated dUTP nick end-labeling
      detection, spermatogonial stem cell transplantation and fertility recovery
      evaluation. Our results showed that spontaneous apoptosis was observed in normal
      rats' testes from the control group with an apoptotic index (AI) average of
      10.24+/-1.52. In the regimen-treated group, the predominant apoptotic cells were
      spermatocytes and spermatids in the seminiferous tubules. Spermatogonia were not
      apoptotic (AI averaged 113.42+/-13.24). Two to three months after transplantation
      of spermatogonial stem cells isolated from regimen-treated rats into recipient
      nude mice, elongated rat spermatids were identified in the seminiferous tubules
      of recipient nude mice. Six weeks after withdrawal of the administration,
      fertility of the regimen-treated rats was recovered compared with that of the
      control group. The number of litters produced by females mated with regimen
      treated males averaged 9.88+/-0.166 matched 10.30+/-0.171 of control group and
      the litters of the first generation appeared to be normal. These results
      indicated that the administration of this regimen did not affect the existence
      and differentiation potential of spermatogonial stem cells of the regimen-treated
      rats.

PMID- 17453690
TI  - Sole use of sucrose in human sperm cryopreservation.
AB  - Glycerol alone or in combination with other additives is one of the most widely
      used and successful cryoprotectants for human sperm. The glycerol method requires
      rigorous post thaw sample washing for use in ART and this may lead to low sperm
      yield from oligospermic samples. In this study the feasibility of the use of
      sucrose in sperm cryopreservation was explored. Sucrose as cryoprotectant was
      combined with direct plunging of sample into liquid nitrogen (vitrification) as a
      freezing method. Sucrose treated sperm from normozoospermic and severly
      oligozoospermic samples underwent rapid freeze and thaw. Motility and viability
      were evaluated before freezing (after sucrose equilibration) as well as post
      freezing (after thaw). The 100 mM concentration of sucrose showed better
      cryoprotectant features compared to that of higher concentrations (200-1000 mM).
      Sucrose (100 mM)treated sperm maintained low but acceptable motility (30%) and
      satisfactory viability (60%) after freezing and thawing. The cryoprotectant
      capacity of sucrose for normozoospermic and oligozoospermic samples were
      identical. The sucrose method utilizes rapid freezing of a micro volume of sample
      and thus quickly freezes, thaws, and maximizes recovery of the sperm from the
      sample.

PMID- 17453691
TI  - Hypothesis: safety of using mobile phones on male fertility.

PMID- 17453692
TI  - The epidemiology and phenomenology of non-suicidal self-injurious behavior among
      adolescents: a critical review of the literature.
AB  - This article critically reviewed the research addressing the epidemiology and
      phenomenology of non-suicidal self-injury (NSSI) among adolescents. Articles were
      identified through a search of Medline and Psychinfo. Findings indicate a
      lifetime prevalence of NSSI ranging from 13.0% to 23.2%. Reasons for engaging in
      NSSI include to regulate emotion and to elicit attention. Correlates of NSSI
      include a history of sexual abuse, depression, anxiety, alexithymia, hostility,
      smoking, dissociation, suicidal ideation, and suicidal behaviors. Suggested areas
      of future research include identifying the psychiatric diagnoses associated with
      NSSI among adolescents, determining the temporal link between NSSI and suicide
      attempts, learning more about the course of NSSI, understanding the biological
      underpinnings of NSSI, and identifying effective treatments for NSSI in
      adolescents.

PMID- 17453693
TI  - Aircraft-assisted pilot suicides in the United States, 1993-2002.
AB  - Our laboratory was interested in epidemiological and toxicological findings from
      aircraft-assisted pilot suicides. Between 1993-2002 there were 3,648 fatal
      aviation accidents. The NTSB determined that 16 were aircraft-assisted suicides;
      15 from intentional crashing of an aircraft and 1 from exiting the aircraft while
      in-flight. All pilots involved in these aircraft-assisted suicides were male,
      with a median age of 40 years. Seven of the 14 pilots for which specimens were
      available were positive for disqualifying substances. Based on the few cases
      conclusively attributed to suicide, death by the intentional crashing of an
      aircraft appears to be an infrequent and uncommon event.

PMID- 17453694
TI  - Continued antidepressant treatment and suicide in patients with depressive
      disorder.
AB  - Antidepressant use in Denmark, as in many developed countries, has substantially
      increased during recent years, coinciding with a decreasing suicide rate. In a
      nationwide observational cohort study with linkage of registers of all prescribed
      antidepressants and recorded suicides in Denmark from 1995 to 2000, we
      investigated the relation between continued treatment with antidepressants and
      suicide in a population of all patients discharged from hospital psychiatry with
      a diagnosis of depressive disorder. Patients discharged from hospital psychiatry
      with a diagnosis of depressive disorder had a highly increased rate of suicide.
      Those who continued treatment with antidepressants had a decreased rate of
      suicide compared with those who purchased antidepressants once (rate ratio: 0.31,
      95% confidence interval: 0.26-0.36). Further, the rate of suicide decreased
      consistently with the number of prescriptions. On individualized data from a
      cohort of patients with a known history of depressive disorder, continued
      antidepressant treatment was associated with reduced risk of suicide.

PMID- 17453695
TI  - Optimism and suicide ideation among young adult college students.
AB  - Given that college students may be at increased risk for suicide, it is important
      to conduct research that could guide suicide prevention efforts on college
      campuses. Although much research has been conducted on the role of hopelessness
      and depression in suicide ideation, the role of dispositional optimism is
      unclear. Subjects were 284 college students (185 female, 65%), ages 18 and over.
      Optimism was assessed with the Life Orientation Test-Revised. The outcome measure
      was the Beck Scale for Suicide Ideation. A hierarchical, multivariate regression
      was used to test the hypothesis that optimism is inversely associated with
      suicide ideation, even after controlling for age, gender, depressive symptoms,
      and hopelessness. The hypothesis was supported. Optimism holds promise as a
      cognitive characteristic associated with decreased thoughts of suicide in college
      students; a better understanding of its putative protective role in this group,
      and cross-culturally, is needed. Prevention programs designed to enhance optimism
      in the college setting might decrease suicide risk.

PMID- 17453696
TI  - The relationship between CSF HVA/5-HIAA ratio and suicide intent in suicide
      attempters.
AB  - There is a need to find stable biomarkers for suicidal behavior and suicide
      prediction. Reduced homovanillic acid/5-hydroxyindolacetic acid (HVA/5-HIAA)
      ratios in cerebrospinal fluid (CSF) in depressed suicide attempters have been
      reported. Suicide intent is a predictor of repetition of attempts and suicide. In
      the present study we investigated the relationship of HVA/5-HIAA ratio to the
      scales rating suicide intent and depressive symptoms. Fifteen consecutive
      medication-free male suicide attempters admitted to a psychiatric ward at the
      Karolinska Hospital and eight healthy male volunteers underwent lumbar puncture
      and had the CSF monoamine metabolite levels assayed. Patients were assessed with
      the Beck Suicide Intent Scale (SIS), the Montgomery Asberg Depression rating
      Scale (MADRS) and the Chapman Scale of Anhedonia. Within the suicide attempter
      group, HVA/5-HIAA ratio was significantly associated with the Suicide Intent
      Scale (SIS), but not with the MADRS scale or the Chapman Scale of Anhedonia
      indicating that the HVA/5-HIAA ratio may be a biomarker of suicide intent.

PMID- 17453697
TI  - Body uneasiness and suicide risk in a non-clinical sample of university students.
AB  - Attitudes and feelings towards the body may be a source of pleasure and well
      being; on the other hand, bodily dissatisfaction may lead to suffering,
      depression and even suicide. The study population consisted of 500 university
      students (190 males, 310 females); mean age of participants was 21.62 (SD =
      2.70). Participants were assessed by means of the Body Uneasiness Test (BUT), the
      Reason for Living Inventory (RFL), and the Zung Self Depression Scale (SDS). Data
      underline a linear relationship between uneasiness linked to body image and
      possible suicide risk. Such evidence suggests that body uneasiness can be a
      source of psychological pain and in serious cases expose the individuals to an
      increased suicide risk. Yet, depression was the strongest correlate of increased
      suicide risk.

PMID- 17453698
TI  - Psychometric properties of the scale for suicide ideation in China.
AB  - The Chinese version of Scale for Suicide Ideation (SSI; Beck, Kovacs, & Weissman,
      1979) was examined with high school students (n = 292) in rural China. Results
      indicated that the SSI had high internal reliability and high item-total
      correlations. The SSI was highly correlated with measures of trait anxiety,
      hopelessness, and favorable attitude towards suicide. These findings indicated
      that the Chinese version of the SSI has excellent psychometric properties for
      measuring suicidal ideation in Chinese populations.

PMID- 17453699
TI  - Risk factors for suicide attempts among alcohol dependent patients.
AB  - Suicidal behavior is a common and important problem among alcohol dependent
      patients. The study was designed to examine risk factors for attempting suicide
      in 499 alcohol dependent patients. Those who had attempted suicide (N = 198) were
      more likely to be female, report a family history of suicidal behavior, report
      more childhood trauma, report greater levels of aggressive behavior, began heavy
      drinking earlier, and were more likely to have received antidepressant
      medication. Logistic regression analysis showed that gender, family history, and
      childhood sexual abuse history made significant and independent contributions to
      the risk of a suicide attempt. Thus, developmental, personality, family history,
      social, and comorbidity risk factors may differentiate alcohol dependent patients
      who have attempted suicide from those who have not.

PMID- 17453700
TI  - The development and validation of statistical prediction rules for discriminating
      between genuine and simulated suicide notes.
AB  - The suicide note is a valuable source of information for assisting police forces
      in equivocal death investigations. The present study endeavored to develop
      statistical prediction rules to discriminate between genuine and simulated
      suicide notes. Discriminant function analysis was performed on a sample of 33
      genuine and 33 simulated notes to identify variables that serve as best
      predictors of note authenticity. Receiver operating characteristic analysis was
      then applied to validate these models and establish decision thresholds. The
      optimal model yielded an accuracy score of .82, with average sentence length and
      expression of positive affect being particularly effective at discriminating
      between the notes. Theoretical implications are discussed as are the practical
      advantages of applying receiver operating characteristic analysis in the
      investigation of equivocal deaths.

PMID- 17453701
TI  - Perceptions in transfusion medicine: a pilot field study on risk and ethics for
      blood and blood substitutes.
AB  - A pilot study was undertaken in the UK in February 2005 to identify the
      perceptions of risk, effectiveness and ethicality of different hypothetical
      transfusion options, including blood substitutes derived from different sources,
      among young adults. Forty-nine men and 92 women completed the questionnaire,
      aging between 18 and 25 years old (mean +/- standard deviation = 19.7 +/- 1.2
      years). Twenty-three percent of respondents had donated blood, an average of 3.1
      times. The study assessed the perceptions of donor blood versus 3 different types
      of potential "artificial blood" [i.e. "chemical" (synthetic), "grown from
      bacteria" (recombinant hemoglobin), or "based on cow blood" (bovine hemoglobin)]
      on three dimensions, namely risk, effectiveness, and ethicality, each scored on a
      1 (least) to 7 (most) Likert-type scale. Donor blood was rated as significantly
      (P < 0.05) less risky, more effective and more ethical than any of the blood
      substitutes. The chemical-based blood substitute was rated second least risky,
      second most effective and second most ethical followed by bacteria grown
      substitute. The bovine-based blood substitute was rated as significantly riskier,
      least effective and least ethical. All the blood products differed significantly
      for perceived ethicality, with donor blood considered as most ethical and a blood
      substitute derived from bovine blood as least ethical. Judgments of risk
      correlated negatively with effectiveness (all transfusion options) and ethicality
      (all the blood substitutes). Overall, these results indicate that donor blood is
      currently preferred over blood substitutes in the UK and that judgments of risk
      about different hypothetical transfusion options are related to perceptions of
      effectiveness and ethicality.

PMID- 17453702
TI  - Effects of hemoglobin vesicles, a liposomal artificial oxygen carrier, on
      hematological responses, complement and anaphylactic reactions in rats.
AB  - Hemoglobin vesicle (HbV), a liposomal oxygen carrier containing human hemoglobin,
      was intravenously infused into rats. After the infusion of saline, the HbV or
      empty vesicle (EV), numbers of red cells, leukocytes and platelets in peripheral
      blood were unchanged during the observation period of one week in addition to
      each time point among three groups. However, the lymphocyte ratio transiently
      decreased and the granulocyte ratio increased in the HbV and EV groups at 6 h
      after the infusion. Those changes returned to the initial value one day after the
      infusion and those were maintained for the subsequent observation period. No
      dramatic change was seen in the ratio of CD4(+)/CD8(+) T cells. A transient
      decrease of the complement titer was observed three days after the infusion of
      HbV and EV, although the consumption of complement titer was not detected in rat
      serum by mixing HbV or EV in vitro, indicating that the transient decrease of
      complement titer in vivo was not due to the consumption of complement due to the
      interaction with HbV or EV. Multiple infusions of HbV caused the decrease of
      complement titer only after the first infusion and no allergic reaction was
      observed. No anaphylactic shock was observed in rats administered with EV several
      times, while ovalbumin (OVA) sensitized rats died with symptoms of respiratory
      distress after the second OVA administration. These results indicate that HbV
      could be administered without serious clinical symptoms or adverse reactions.

PMID- 17453703
TI  - Comparison of treatment modalities for hemorrhagic shock.
AB  - Allogeneic blood resuscitation is the treatment of choice for hemorrhagic shock.
      When blood is unavailable, plasma expanders, including crystalloids, colloids,
      and blood substitutes, may be used. Another treatment modality is vasopressin, a
      vasoconstrictor administered to redistribute blood flow, increase venous return,
      and maintain adequate cardiac output. While much information exists on systemic
      function and oxygenation characteristics following treatment with these
      resuscitants, data on their effects on the microcirculation and correlation of
      real-time microvascular changes with changes in systemic function and oxygenation
      in the same animal are lacking. In this study, real-time microvascular changes
      during hemorrhagic shock treatment were correlated with systemic function and
      oxygenation changes in a canine hemorrhagic shock model (50-55% total blood loss
      with a MAP of 45-50 mmHg as a clinical criterion). Following splenectomy and
      hemorrhage, the dogs were assigned to five resuscitation groups: autologous/shed
      blood, hemoglobin-based oxygen carrier/Oxyglobin, crystalloid/saline,
      colloid/Hespan (6% hetastarch), and vasopressin. Systemic function and
      oxygenation changes were continuously monitored and periodically measured (during
      various phases of the study) using standard operating room protocols. Computer
      assisted intravital video-microscopy was used to objectively analyze and quantify
      real-time microvascular changes (diameter, red-cell velocity) in the conjunctival
      microcirculation. Measurements were made during pre-hemorrhagic (baseline), post
      hemorrhagic (pre-resuscitation), and post-resuscitation phases of the study. Pre
      hemorrhagic microvascular variables were similar in all dogs (venular diameter =
      42+/-4 microm, red-cell velocity = 0.55+/-0.5 mm/sec). All dogs showed
      significant (P < 0.05) post-hemorrhagic microvascular changes: approximately 20%
      decrease in venular diameter and approximately 30% increase in red-cell velocity,
      indicative of sympathetic effects arising from substantial blood loss.
      Microvascular changes correlated with post-hemorrhagic systemic function and
      oxygenation changes. All resuscitation modalities except vasopressin restored
      microvascular and systemic function changes close to pre-hemorrhagic values.
      However, only autologous blood restored oxygenation changes to pre-hemorrhagic
      levels. Vasopressin treatment resulted in further decreases in venular diameter
      (approximately 50%) as well as red-cell velocity (approximately 70%) without
      improving cardiac output. Our results suggested that volume replenishment - not
      oxygen-carrying capability - played an important role in pre-hospital/en route
      treatment for hemorrhagic shock. Vasopressin treatment resulted in inadvertent
      detrimental outcome without the intended benefit.

PMID- 17453704
TI  - Evaluation of angiotensin converting enzyme (ACE)-like activity of acellular
      hemoglobin.
AB  - Despite the tremendous progress in research on hemoglobin (Hb) cellular and
      molecular responses, the current understanding of Hb's overall intrinsic toxicity
      is still limited. The complete mechanism of Hb-induced vasoconstriction has not
      yet been established, particularly the involvement of the renin-angiotensin
      system (RAS). Some studies emphasized that Hb may augment the vascular
      responsiveness to angiotensin (Ang)-II. It was also reported that Hb, as well as
      Ang-II, influences the synthesis of 8-iso prostaglandin F2 alpha, which has an
      impact on renal flow and possibly RAS. Hb in the presence of H(2)O(2) gains
      enzymatic activity. Thus, it is possible that Hb directly and/or indirectly can
      activate RAS. In this study, we monitored the effect of ferrous- and ferryl-Hb,
      and H(2)O(2) alone, on conversion of Ang-I to its active metabolites. The
      structural and immunological identity of the resulting products were evaluated by
      reversed phase C-18 HPLC and ELISA, respectively. Additionally, ACE-like activity
      of Hbs was measured spectrophotometrically by determining their ability to react
      with the ACE substrate, the synthetic tripeptide N-[3-(2-furyl)acryloyl]-L
      phenylalanylglycylglycine. Results indicate that while ferrous-Hb can serve as a
      receptor for Ang-I, its ferryl form possesses ACE-like activity, being able to
      convert, within minutes, Ang-I to Ang-II, Ang-III, Ang-IV, Ang (1-7) and other
      unresolved fragments. H(2)O(2) itself had a very limited hydrolyzing effect on
      Ang-I. Based on this study, it can be concluded that ACE-like activity of Hb with
      rapid formation of active angiotensins may be a contributor to the still
      unexplained vasoconstrictive response observed immediately after Hb
      administration.

PMID- 17453705
TI  - Potential use of fluorocarbons in lung surfactant therapy.
AB  - Exogenous surfactant therapy based on animal lung extract preparations has been
      developed successfully for the treatment of neonatal respiratory distress
      syndrome. However, because of the inherent limitations of these natural
      preparations, the development of new synthetic surfactants is a major objective.
      We report here that a perfluorocarbon gas (perfluorooctyl bromide, gPFOB)
      inhibits the formation of the semi-crystalline domains that occur during
      compression of a Langmuir monolayer of dipalmitoyl phosphatidylcholine (DPPC),
      taken as a simplified model of lung surfactant. gPFOB also facilitates the re
      spreading of the DPPC monolayer. These results suggest that PFOB, a fluorocarbon
      already investigated for oxygen delivery, may be useful in lung surfactant
      replacement compositions.

PMID- 17453706
TI  - Immobilization of Candida rugosa lipase on magnetized Dacron: kinetic study.
AB  - Candida rugosa lipase has been covalently immobilized on ferromagnetic azide
      polyethyleneterepthalate (Dacron) with specific activity retention of 16% for 4
      nitrophenyl palmitate and 24% for hydrolysis of triolein in hexane. The
      immobilized enzyme was more thermal stable than the soluble one, retaining 78.8%
      of the activity after 1 h at 60 degrees C. Also, this immobilized derivative was
      stable at the storage at 4 degrees C. It has been used 5 cycles for pNPP
      hydrolysis without loss of activity. Soluble and immobilized Candida rugosa
      lipase showed a Michaelian behavior for fatty acid 4-nitrophenyl esters and
      different apparent K(M) values: 0.110 mM and 0.124 mM (4-nitrophenyl palmitate -
      C16); 0.193 mM and 0.235 mM (4-nitrophenyl laurate - C12) and 0.206 mM and 0.119
      mM (4-nitrophenyl butyrate - C4), respectively. The immobilized lipase was more
      efficient for catalyzing the hydrolysis of 4-nitrophenyl esters with short chain
      length fatty acid (4-NPB - C4) than soluble enzyme. The ferromagnetic Dacron
      lipase derivative was able to catalyze the synthesis of triolein from glycerol
      and oleic acid with 50% of conversion after 72 h at 40 degrees C.

PMID- 17453707
TI  - SARS-CoV nucleocapsid protein induced apoptosis of COS-1 mediated by the
      mitochondrial pathway.
AB  - To investigate the apoptosis effect of SARS coronavirus nucleocapsid protein on
      cultured cell lines and to explore the possible pathway of apoptosis. pCDNA3.1(
      )/his-myc vector containing the SARS coronavirus nucleocapsid gene (N), matric
      gene (M), spike gene (S) were transfected into COS-1, Huh-7 and HepG2 cells.
      Apoptosis induced by SARS coronavirus N protein under starvation of serum of COS
      1 cells was monitored by Annexin V and electron microscopy assays. Intracellular
      reactive oxygen species (ROS) and mitochondrial membrane potential (DeltaPsim)
      were determined by flow cytometric assay. Cytochrome C, cleaved caspase (cysteine
      aspartic acid protease)-3, 9, and poly (ADP-ribose) polymerase (PARP) were
      detected by Western blot. After removal of serum in COS-1 cells, we observed the
      loss of DeltaPsim, the increase of ROS and cytochrome C release into cytosol and
      subsequent activation of caspase-3 and PARP cleavage. The pan-caspase inhibitor z
      VAD-fmk can block the activation of caspase 3, 9 and PARP cleavage. In
      conclusion, SARS coronavirus N protein can induce apoptosis of COS-1 cells by
      activating mitochondrial pathway. SARS coronavirus M, S protein can not induce
      apoptosis in COS-1, HepG2 and Huh-7 and SARS coronavirus N protein can not induce
      apoptosis in HepG2 and Huh-7 by methods used in this study.

PMID- 17453709
TI  - Physiological and pathological implications of laminins: from the gene to the
      protein.
AB  - The extracellular matrix plays an important role in modulating the behavior of
      cells with which it interacts. There are a number of families of extracellular
      matrix (ECM) proteins including collagens, proteoglycans and laminins (LM). LM
      are the major component of the basal lamina (BL). Here, we review the current
      knowledge on their structure, self-assembly, binding mechanisms, diverse tissue
      expression patterns and its impact on pathology. Studies and hypothesis exploring
      the role of LM and their polymorphic genes on autoimmune diseases (AIDs) such as
      systemic lupus erythematosus and Sjogren's syndrome (SS) are also discussed.

PMID- 17453710
TI  - Allograft inflammatory factor-1 and its immune regulation.
AB  - The allograft inflammatory factor-1 (AIF-1) is a 17 kDa interferon-gamma (IFN
      gamma) inducible Ca(2+)-binding EF-hand protein that is encoded within the HLA
      class III genomic region. Three proteins including ionized Ca(2+)-binding adaptor
      1, microglia response factor-1, and daintain are identical with AIF-1. The
      expression of AIF-1 was mostly limited to the monocyte/macrophage lineage, and
      augmented by cytokines such as IFN-gamma. It was assumed that AIF-1 was a novel
      molecule involved in inflammatory responses, allograft rejection, as well as the
      activation and function of macrophages. However, it has been reported that AIF-1
      is also expressed in macrophages and microglial cells in autoimmune diseases such
      as experimental autoimmune encephalomyelitis, neuritis and uveitis models,
      suggesting that AIF-1 may play a pivotal role in autoimmunity. In the present
      manuscript, the genomic and functional characteristics of AIF-1 family proteins
      as well as their immune regulatory effects are reviewed.

PMID- 17453711
TI  - Autoimmune responses against the apo B-100 LDL receptor-binding site protect
      against arterial accumulation of lipids in LDL receptor deficient mice.
AB  - BACKGROUND: Oxidation of LDL is associated with generation of autoantibodies
      against a large number of different aldehyde-modified peptide sequences in apo B
      100. Autoantibodies recognizing peptide sequences in the LDL receptor-binding
      region of apo B-100 could potentially affect both cholesterol metabolism and
      atherosclerosis. The aim of the present study was to determine physiological
      effects of induction of immune responses against the apo B-100 LDL receptor
      binding site in mice deficient for the LDL receptor. METHODS AND RESULTS: Mice
      received three immunizations, beginning at 6 weeks of age, with aldehyde-modified
      or non-modified peptides corresponding to the amino acid sequence of the LDL
      receptor-binding site. Analysis of antibody response by ELISA unexpectedly
      revealed high titers of pre-existing IgG against both native and aldehyde
      modified binding site sequences in non-immunized mice. Immunization with aldehyde
      modified binding site sequences resulted in an almost complete down-regulation of
      this autoimmune response. It was also associated with a rapid increase in lipid
      rich plaques in the aorta and a substantial depletion of the lipid content of the
      liver, whereas plasma lipid and apo B values were similar in all groups.
      CONCLUSIONS: These observations demonstrate existence of an endogenous T cell
      dependent autoimmune response against the LDL receptor-binding site in LDL
      receptor(-/-) mice and suggest that this may help to prevent accumulation of
      lipoprotein lipids in the artery wall, whereas immunization with the
      corresponding aldehyde modified sequence down-regulates this response and induces
      substantial atherosclerotic development.

PMID- 17453712
TI  - Altered immunogenicity of isoaspartate containing proteins.
AB  - The development of immune tolerance is dependent on the expression of self
      peptides in the thymus and bone marrow during lymphocyte development. However,
      not all self-antigens are expressed in the thymus, particularly for proteins that
      become post-translationally modified during other biological processes in a cell.
      We have found that one such post-translational modification, the spontaneous
      conversion of an aspartic acid to isoaspartic acid (isoAsp), causes ignored self
      antigens to become immunogenic. In order to determine the mechanism for this
      autoimmune response, pigeon cytochrome c peptide 88-104 (PCC p88-104) was
      synthesized with and without an isoaspartyl residue. Each form was digested with
      cathepsin D, an enzyme involved in antigen processing. The products of cathepsin
      digestion were dramatically different between the two forms of self-protein
      suggesting that cryptic self-peptides may be revealed to the immune system by
      natural modifications to self-proteins. This observation also held true if whole
      PCC protein contained isoaspartyl residues was digested with cathespsin D.
      Additionally, AND transgenic TCR T cells (recognizing PCC 88-104) proliferated to
      a greater extent in response to isoaspartyl PCC as compared to the normal form of
      PCC. These finding demonstrate the importance of post-translational modifications
      in shaping autoimmune responses in and the development of tolerance to self
      proteins.

PMID- 17453713
TI  - The blood-brain-barrier in multiple sclerosis: functional roles and therapeutic
      targeting.
AB  - In most regions of the central nervous system (CNS), the composition of the
      neuronal microenvironment is maintained by virtue of particular blood-brain
      barrier (BBB) characteristics, to which vascular endothelial cells (ECs)
      contribute an important role. Multiple sclerosis (MS) is an inflammatory
      demyelinating disease of the CNS, characterized at tissue level by multifocal
      perivascular infiltrates, predominantly of lymphocytes and macrophages. Thus,
      lymphocyte recruitment into the brain across ECs of the BBB represents a critical
      event in disease pathogenesis, which is highly restricted and carefully
      regulated. In recent years, different investigations have identified the crucial
      components involved in leukocyte migration, providing new insights into
      mechanisms modulating neuroinflammatory reactions. In this review, several topics
      relating to these events are discussed, namely: (1) cellular and molecular
      characteristics of the BBB regulating permeability, as well as signals inducing
      EC differentiation in the brain and specific cell properties; (2) pathogenic
      mechanisms guiding the migration of different leukocyte populations through the
      BBB in MS; and (3) current knowledge on how different MS therapies targeting
      leukocytes migration across the BBB function. Furthermore, because the BBB has
      proven to be an important retaining wall preventing drug passage into the CNS,
      novel strategies directed at successful delivery of large molecules for effective
      treatment of various inflammatory conditions of the brain, both currently
      available or still under development, are discussed.

PMID- 17453714
TI  - Determination of ligand binding capacity of soluble Fc gamma RII and Fc gamma
      RIII in sera of patients with SLE.
AB  - BACKGROUND: Soluble, human low affinity Fcgamma receptors, such as sFcgammaRII
      and sFcgammaRIII, are known to play a pathologic role in different diseases.
      Sandwich ELISAs had previously been applied for the specific detection and
      determination of these soluble receptors. In these ELISAs, commercial monoclonal
      antibodies (Ab) were used as capture antibodies with monoclonal or polyclonal
      antibodies serving as detector Abs. Increased levels of cell-free FcgammaRIII
      have been detected in patients with lupus but the functions and levels of
      sFcgammaRII have not been fully characterized yet. OBJECTIVES: The aim of this
      work was to determine the ligand binding capacities and levels of soluble
      FcgammaRII and FcgammaRIII in sera of patients with systemic lupus erythematosus
      (SLE). Moreover, correlation between the levels of sFcgammaRII and sFcgammaRIII
      and the clinical activity of the disease were investigated. METHODS: Sera of 47
      patients with SLE, and 51 healthy subjects were analyzed. In the newly developed
      indirect sandwich ELISAs commercial monoclonal anti-FcgammaRs are used as capture
      antibodies, and the ligand of FcgammaRII and FcgammaRIII, an artificial immune
      complex (IC), serves as a detection component replacing the second antibodies
      used in previous methods. RESULTS: The ligand binding capacity of both soluble
      FcgammaRII and sFcgammaRIII were elevated in the sera of SLE patients compared to
      control samples. This increase was significant in patients with the active
      disease (n = 30; p < 0.01). It was also revealed that a substantial part of the
      soluble Fcgamma receptors in these patients was bound in vivo to circulating IC.
      CONCLUSION: These newly developed ELISAs are probably more phisiologically
      relevant than other previous assays because they detect the circulating receptors
      on the basis their in vitro ligan binding capacities. Therefore this method can
      separately measure the levels of the soluble, free FcgammaRs and those bound
      circulating IC in vivo.

PMID- 17453715
TI  - Autoimmunity in HLA-DQ8 transgenic mice expressing granulocyte/macrophage-colony
      stimulating factor in the beta cells of islets of Langerhans.
AB  - Type 1 diabetes (T1D) is a polygenic autoimmune disease with a strong HLA
      association particularly, HLA-DQ8. We investigated whether islet-specific
      expression of granulocyte/macrophage colony-stimulating factor (Ins.GM-CSF) in A
      Beta degrees.NOD.DQ8 mice (HLA-DQ8 transgenic mice on a NOD background lacking
      endogenous mouse MHC class II molecules) would predispose to development of
      spontaneous autoimmune diabetes. A Beta degrees.NOD.DQ8 mice expressing GM-CSF in
      the pancreatic ss cells (8+ G+) as well as litter mates lacking either HLA-DQ8 (8
      - G+) or GM-CSF (8+ G -) or both (8 - G -) exhibited insulitis and sialadenitis
      of varying degrees. But none of the mice progressed to develop T1D. Other than
      the marked mononuclear cell infiltration in livers of mice expressing GM-CSF
      irrespective of HLA-DQ8 expression (8+ G+ or 8 - G+), no other changes were
      observed in the animals. Thus, we have shown for the first time that expression
      of HLA-DQ8 in the diabetes-predisposing mileu of NOD genetic background is not
      sufficient to predispose to development of autoimmune diabetes even when the
      potent immunostimulatory cytokine, GM-CSF is expressed in the pancreatic islets.

PMID- 17453716
TI  - Propofol hemisuccinate suppression of experimental autoimmune encephalomyelitis.
AB  - Propofol hemisuccinate is a prodrug water soluble form of the lipophilic,
      phenolic compound propofol (2,6-di-isopropylphenol), that is the active
      ingredient in the widely used anesthetic agent Diprovan. Propofol binds to
      GABA(A) receptors but also has a phenolic structure that confers antioxidant
      properties to the molecule. The effects of propofol hemisuccinate in rat
      experimental autoimmune encephalomyelitis (EAE) were studied using different
      doses and time regimes. Propofol hemisuccinate, 100 mg/kg given three times a day
      from day 7 or day 12 until day 16 after disease initiation, significantly reduced
      maximal EAE score. Histology studies supported the clinical findings
      demonstrating reduction in the inflammatory response in the lumbar spinal cord in
      animals treated with propofol hemisuccinate. Decreased levels of nitrotyrosine
      and unchanged levels of induced nitric oxide synthase suggest propofol
      hemisuccinate crossed the blood brain barrier and exerted its effects by lowering
      reactive oxygen species levels. The results suggest that propofol hemisuccinate
      may provide an alternative mode of treatment for acute exacerbations of multiple
      sclerosis.

PMID- 17453717
TI  - The association between HLA genes and radiological erosions in Malaysian patients
      with rheumatoid arthritis.
AB  - OBJECTIVE: To assess the relationship between the HLA-DRB1 genes with disease
      severity as assessed by radiological erosions in Malaysian patients with
      rheumatoid arthritis (RA). METHODS: In this cross-sectional study, we studied 61
      RA patients who fulfilled the ACR criteria for the diagnosis of RA. HLA-DRB1
      genotyping was performed by sequence specific primer (SSP) - PCR. Radiological
      grading and erosive score of the hands and wrists was calculated according to the
      Larsen-Dale method. Demographic data and treatment given to the patients were
      obtained from their case records. RESULTS: Fifty-six females and five males were
      studied from three ethnic groups. In 57 patients with erosions, rheumatoid factor
      was detected in 80%, HLA-DR4 in 40%, HLA-DRB1*0405 in 24% and shared epitope (SE)
      in 31%. The median delay in starting DMARDs was 24 months. The presence of
      rheumatoid factor, HLA-DR4 and HLA-DRB1*0405 were not significantly associated
      with a worse erosive score. Patients who possessed the SE had a higher erosive
      scores, compared to those who did not (p = 0.05). Concurrently, a delay in
      starting DMARD was associated with a high erosive score (p = 0.023, r = 0.348).
      However, after adjustment for the delay in starting DMARD, SE was no longer
      significantly associated with the erosive score. CONCLUSIONS: In these patients,
      the delay in starting DMARDs had a greater influence on the erosive score than SE
      alone. Whilst we cannot discount the contribution of the SE presence, we would
      advocate early usage of DMARDs in every RA patient to reduce joint erosions and
      future disability.

PMID- 17453718
TI  - Gene expression profiling in autoimmune diseases: chronic inflammation or disease
      specific patterns?
AB  - A central issue in autoimmune disease is whether the underlying inflammation is a
      repeated stereotypical process or whether disease specific gene expression is
      involved. To shed light on this, we analysed whether genes previously found to be
      differentially regulated in rheumatoid arthritis (RA) patients and healthy
      individuals were specific for the arthritic process or likewise altered in other
      chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's
      thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA
      discriminative genes, there were no significant differences in peripheral blood
      mononuclear cell (MNC) gene expression patterns between 15 newly diagnosed HT
      patients and 15 matched healthy controls. However, the MNC expression levels of
      five genes were significantly upregulated in 25 IBD patients, compared to 18
      matched healthy controls (CD14, FACL2, FCN1, RNASE2, VNN2). There was concordance
      in the directional change for all genes between IBD and RA patients, i.e.
      increased expression compared to controls. These data show that one third of the
      genes significantly upregulated in MNC from RA patients were upregulated in
      patients with other chronic immunoinflammatory diseases, but only if accompanied
      by pronounced systemic manifestations. This suggests that at least some of the
      genes activated in RA are predominantly or solely related to general and disease
      nonspecific autoimmune processes.

PMID- 17453719
TI  - Antibodies to myelin protein zero (P0) protein as markers of auto-immune inner
      ear diseases.
AB  - BACKGROUND/AIMS: The inner ear can be the target of autoimmune disorders.
      Recognition of autoimmune inner ear disease is important, as it is one of the
      very few forms of sensorineural hearing loss (HL) that can be successfully
      treated by medical therapy. The aim of this study was to evaluate whether the
      detection of antibodies to myelin protein P0 (MPZ) could be a diagnostic test for
      inner ear disease of autoimmune cause. METHODS: This multicentric prospective
      study included 129 patients: patients with progressive sensorineural HL or with
      Meniere's disease, together with their control group corresponding to patients
      with similar symptoms, but of presumably known origin. Detection of antibodies to
      myelin P0 protein was performed by using western blots. NORMAL: The prevalence of
      antibodies to myelin P0 protein in patients with rapidly progressive HL was not
      statistically different from that of the control group corresponding to genetic
      HL patients (30 versus 28%). In patients with Meniere's disease, the prevalence
      was lower than that of the control group corresponding to patients with benign
      paroxysmal positional vertigo (5.4 versus 18.7%). No patient with auto-immune
      disease had antibodies to myelin P0 protein. CONCLUSIONS: The sole presence of
      antibodies to myelin P0 may not be used as a marker of inner ear disease of
      autoimmune origin.

PMID- 17453720
TI  - Anti-ribonucleoprotein antibodies mediate enhanced lung injury following
      mesenteric ischemia/reperfusion in Rag-1(-/-) mice.
AB  - Natural Abs and autoantibodies bind antigens displayed by ischemia-conditioned
      tissues, followed by complement activation and enhanced tissue injury during
      reperfusion. Anti-ribonucleoprotein (RNP) Ab is associated with lung disease in
      patients with autoimmune disease but it is not known whether these abs contribute
      to lung injury. Mesenteric I/R in mice leads to local and remote lung injury.
      Accordingly, we used this model to investigate whether anti-RNP Abs would
      reconstitute I/R damage with prominent lung damage in injury-resistant Rag1(-/-)
      animals. Rag1(-/-) mice injected with anti-RNP Ab containing serum and subjected
      to mesenteric I/R suffered greater intestinal injury than control-treated and
      sham-operated animals. The magnitude of the reconstituted damage was anti-RNP Ab
      titer-dependent. Anti-RNP Ab-treated animals demonstrated a dose-dependent
      increase in lung histologic injury scores compared to control and sham animals.
      Anti-RNP mediated injury was shown to be complement dependent. These experiments
      reveal a novel mechanism whereby anti-RNP Abs contributes to the development of
      pulmonary pathology in patients with autoimmune diseases following exposure of
      remote organs to I/R injury.

PMID- 17453721
TI  - Selected acute phase proteins and interleukin-6 in systemic lupus erythematosus
      patients treated with low doses of quinagolide.
AB  - The relationship between endocrine regulation and immune system has recently
      become the subject of intense investigations. The objective of this study was to
      determine the extent of selected serum acute phase proteins (APP), IL-6 and
      Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) involvement in
      systemic lupus erythematosus (SLE) patients during quinagolide therapy. A further
      aim of this study was to evaluate the relationships between the above mentioned
      parameters. In 25 SLE patients treated with a low dose of quinagolide (12.5-50
      microg per day) and in 25 healthy persons who constituted the control group,
      serum concentration of C-creative protein (CRP), alpha-1-antitripsin (AAT),
      ceruloplasmin (CER), IL-6 and prolactin (PRL) were estimated at entry and in
      patients after 3 months of treatment. Moreover, SLEDAI score was calculated at
      entry and after 3 months of therapy with quinagolide. IL-6 and PRL levels were
      significantly higher in SLE group whereas the concentrations of CRP, AAT and CER
      were higher than in the controls, but without statistical significance. After 3
      month therapy statistically significant decrease of serum level of IL-6 and PRL
      was revealed. Statistically significant lower serum concentration of CER was also
      obtained after 3 months of therapy whereas serum CRP and AAT concentration was
      lower compared with the mean pretreatment level but the results did not reach
      statistical significance. A raised SLEDAI score at entry was significantly
      reduced after 3 month therapy and positive correlation with PRL level in examined
      group of patients with SLE was noted at entry. The decreased serum concentration
      of IL-6, APP and SLEDAI score observed during applied therapy with small dose of
      quinagolide confirms the hypothesis that quinagolide may become a valuable and
      safe drug in the therapy of patients with mild SLE.

PMID- 17453722
TI  - Multiple specificities of autoantibodies against hnRNP A/B proteins in systemic
      rheumatic diseases and hnRNP L as an associated novel autoantigen.
AB  - Spliceosomal small nuclear ribonucleoproteins (U-snRNPs) are frequent and
      specific targets of autoantibodies in systemic rheumatic diseases. The abundant,
      functionally related heterogeneous nuclear ribonucleoprotein complexes (hnRNPs)
      have later defined as a new target of autoantibodies, of which their
      immunochemical/immunogenic and pathogenic properties are still under
      investigation. Among hnRNP proteins, those belonging to the A/B type are
      considered as the major autoantigens targeted by antibodies in sera of patients
      suffering with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and
      mixed connective tissue disease (MCTD). By performing an extensive screening
      using rat liver 40S hnRNP antigenic material, we document here the existence of
      multiple specificities of anti-hnRNP A/B autoantibodies in sera of Greek patients
      suffering with a spectrum of systemic rheumatic diseases. This included patients
      with SLE, Sjogren's syndrome (SS), Scleroderma (SSc) and a specific group of
      patients mostly with undifferentiated disease (UD patients). In total, four
      distinct types of anti-hnRNP A/B autoantibodies have been recognized. The first
      two referred to the known anti-hnRNPA2(RA33) and anti-hnRNP A1; the latter
      appearing very rarely. The third was of the new type selectively reacting with
      hnRNP B2 and an hnRNP A3 variant, while the fourth was a rare case of anti-hnRNP
      B2 alone. In addition, a novel specificity of autoantibodies against hnRNP L
      protein was identified in association with anti-hnRNP A/B antibodies. The co
      existence within a serum of autoantibodies having variable specificity for hnRNP
      A/B and L autoantigens was shown. Specific immunochemical features of the
      identified autoantibodies are presented and a possible mechanism of autoepitope
      spreading within protein components of hnRNP complexes is discussed.

PMID- 17453724
TI  - Adherent bacteria in heavy metal contaminated marine sediments.
AB  - The eubacterial communities adherent to sediment particles were studied in heavy
      metal contaminated coastal sediments. Six sampling sites on the Belgian
      continental plate and presenting various metal loads, granulometries, and organic
      matter content, were compared. The results indicated that the total microbial
      biomass (attached + free-living bacteria) was negatively correlated to HCl
      extractable metal levels (p<0.05) and that the percentage of cells adherent to
      sediment particles was close to 100% in every site even in highly contaminated
      sediments. Consequently, it seems that heavy metal contamination does affect
      total bacterial biomass in marine sediments but that the ratio between attached
      and free living microorganisms is not affected. The composition of the
      eubacterial communities adherent to the fine fraction of the sediments (<150
      microm) was determined using fluorescent in situ hybridisation (FISH). The FISH
      results indicated that the proportion of gamma- and delta-Proteobacteria, and
      Cytophaga-Flexibacter-Bacteroides (CFB) bacteria, was not related to the HCl
      extractable metal levels. Most of the 79 complete 16S rRNA sequences obtained
      from the attached microbial communities were classified in the gamma- and delta
      Proteobacteria and in the CFB bacteria. A large proportion of the attached gamma
      Proteobacterial sequences found in this study (56%) was included in the
      uncultivated GMS clades that are indigenous to marine sediments.

PMID- 17453725
TI  - Adhesion of facade coating colonisers, as mediated by physico-chemical
      properties.
AB  - The adhesion of Klebsormidium flaccidum, Stichococcus bacillaris and Chlorella
      cf. mirabilis, three strains of green microalgae isolated from biofilms on facade
      coatings were investigated in a parallel plate flow chamber. The model surfaces
      tested were glass slides, and -CH(3) (mediated by octadecyltrichlorosilane [OTS]
      and hexamethyldisilazane [HMDZ] modification) and -NH(2)
      (aminopropyltriethoxysilane [APS] modification) terminated self-assembled
      monolayers. Algal physicochemical properties were evaluated by the microbial
      adhesion to solvents (MATS) assay and by contact angle measurements. The model
      surfaces were characterised by X-ray photoelectron spectroscopy analysis and by
      contact angle measurements. Predicted adhesion trends were then compared to in
      vitro measurements. The adhesion strength of the three algal strains followed the
      trend: APS > OTS > HMDZ > glass. The adhesion process thus seemed to be mediated
      by hydrophobic and electrostatic interactions, and was shown to be influenced by
      the algal culture age and the initial contact time.

PMID- 17453726
TI  - Larval presence prediction through logistic regression: an early warning system
      against Mytilopsis leucophaeata biofouling.
AB  - Mytilopsis leucophaeata is a biofouling bivalve causing major problems in the
      cooling water system of BASF, Antwerp NV, Belgium, a large water-using industrial
      facility. This study aimed to develop a statistical model to predict the response
      of M. leucophaeata larvae to environmental conditions in estuarine ecosystems.
      Multiple logistic regression, taking into account temporal autocorrelation, was
      applied on a large dataset allowing the prediction of the probability of
      occurrence of M. leucophaeata larvae at BASF NV as a response to the
      environmental variables. The final model made it possible to predict larval
      presence in the water column solely by monitoring water temperature. The results
      from subsampling indicated that the model was stable. The model was tested with
      2005 data, demonstrating a 98% precise prediction of the occurrence of M.
      leucophaeata larvae in the water column, with a sensitivity of 100% and a
      specificity of 97%, even though autumn 2005 was exceptionally warm, which led to
      an extended presence of the larvae.

PMID- 17453727
TI  - Combinatorial materials research applied to the development of new surface
      coatings III. Utilisation of a high-throughput multiwell plate screening method
      to rapidly assess bacterial biofilm retention on antifouling surfaces.
AB  - The authors recently reported on the development of a novel multiwell plate
      screening method for the high-throughput assessment of bacterial biofilm
      retention on surfaces. Two series of biocide containing coatings were prepared to
      assess the ability of the developed assay to adequately discern differences in
      antifouling performance: i) a commercially available poly(methyl methacrylate)
      (PMMA) and silicone elastomer (DC) physically blended with an organic antifouling
      biocide Sea-Nine 211 (SN211) (4,5-dichloro-2-n-octyl-3(2H)-isothiazolone), and
      ii) a silanol-terminated polydimethylsiloxane (PDMS-OH) reacted with an alkoxy
      silane-modified polyethylenimine containing bound ammonium salt groups (PEI
      AmCl). Three marine bacteria were utilised to evaluate the SN211 blended coatings
      (Pseudoalteromonas atlantica ATCC 19262, Cobetia marina ATCC 25374, Halomonas
      pacifica ATCC 27122) and the marine bacterium Cytophaga lytica was utilised to
      evaluate the PEI-AmCl/PDMS-OH coatings. The SN211 blended coatings showed a
      general trend of decreasing biofilm retention as the concentration of SN211
      increased in both PMMA and DC. HPLC analysis revealed that reduction in biofilm
      retention was positively correlated with the amount of SN211 released into the
      growth medium over the length of the bacterial incubation. When compared to PMMA,
      DC consistently showed an equal or greater percent reduction in biofilm retention
      as the level of SN211 loading increased, although at lower loading
      concentrations. Evaluations of the PEI-AmCl/PDMS-OH coatings with C. lytica
      showed that all PEI-AmCl loading concentrations significantly reduced biofilm
      retention (p<0.0001) by a surface contact phenomenon. The high-throughput
      bacterial biofilm growth and retention assay has been shown to be useful as an
      effective primary screening tool for the rapid assessment of antifouling
      materials.

PMID- 17453728
TI  - Combinatorial materials research applied to the development of new surface
      coatings IV. A high-throughput bacterial biofilm retention and retraction assay
      for screening fouling-release performance of coatings.
AB  - A high-throughput bacterial biofilm retention screening method has been augmented
      to facilitate the rapid analysis and down-selection of fouling-release coatings
      for identification of promising candidates. Coatings were cast in modified 24
      well tissue culture plates and inoculated with the marine bacterium Cytophaga
      lytica for attachment and biofilm growth. Biofilms retained after rinsing with
      deionised water were dried at ambient laboratory conditions. During the drying
      process, retained biofilms retracted through a surface de-wetting phenomenon on
      the hydrophobic silicone surfaces. The retracted biofilms were stained with
      crystal violet, imaged, and analysed for percentage coverage. Two sets of
      experimental fouling-release coatings were analysed with the high-throughput
      biofilm retention and retraction assay (HTBRRA). The first set consisted of a
      series of model polysiloxane coatings that were systematically varied with
      respect to ratios of low and high MW silanol-terminated PDMS, level of cross
      linker, and amount of silicone oil. The second set consisted of cross-linked PDMS
      polyurethane coatings varied with respect to the MW of the PDMS and end group
      functionality. For the model polysiloxane coatings, HTBRRA results were compared
      to data obtained from field immersion testing at the Indian River Lagoon at the
      Florida Institute of Technology. The percentage coverage calculations of
      retracted biofilms correlated well to barnacle adhesion strength in the field
      (R(2)=0.82) and accurately identified the best and poorest performing coating
      compositions. For the cross-linked PDMS-polyurethane coatings, the HTBRRA results
      were compared to combinatorial pseudobarnacle pull-off adhesion data and good
      agreement in performance was observed. Details of the developed assay and its
      implications in the rapid discovery of new fouling-release coatings are
      discussed.

PMID- 17453729
TI  - Engineered antifouling microtopographies - effect of feature size, geometry, and
      roughness on settlement of zoospores of the green alga Ulva.
AB  - The effect of feature size, geometry, and roughness on the settlement of
      zoospores of the ship fouling alga Ulva was evaluated using engineered
      microtopographies in polydimethylsiloxane elastomer. The topographies studied
      were designed at a feature spacing of 2 microm and all significantly reduced
      spore settlement compared to a smooth surface. An indirect correlation between
      spore settlement and a newly described engineered roughness index (ERI) was
      identified. ERI is a dimensionless ratio based on Wenzel's roughness factor,
      depressed surface fraction, and the degree of freedom of spore movement. Uniform
      surfaces of either 2 mum diameter circular pillars (ERI=5.0) or 2 microm wide
      ridges (ERI=6.1) reduced settlement by 36% and 31%, respectively. A novel multi
      feature topography consisting of 2 mum diameter circular pillars and 10 microm
      equilateral triangles (ERI=8.7) reduced spore settlement by 58%. The largest
      reduction in spore settlement, 77%, was obtained with the Sharklet AF topography
      (ERI=9.5).

PMID- 17453730
TI  - A novel application of Fourier-transformed infrared spectroscopy: classification
      of slime from staphylococci.
AB  - It has been proposed that the virulence of nosocomial Staphylococcus infections
      associated with indwelling medical devices is related to the ability of the
      bacterium to colonise these materials by forming a biofilm composed of
      multilayered cell clusters embedded in a slime matrix. However, the pathogenic
      role of exopolysaccharide biofilms is not fully understood. A new method was
      sought for differentiating the structure of slime from two closely related
      bacterial strains, Staphylococcus aureus and Staphylococcus epidermidis. Using
      PCR it was confirmed that these strains were positive for the icaA and icaD genes
      and the complete ica operon (2.7 kb). Monosaccharide analysis by thin-layer
      chromatography revealed an identical profile for both strains, with xylose and
      glucose present among the four visible bands. Using Fourier-transformed infrared
      spectroscopy and hierarchical cluster analysis, three of four S. aureus samples
      (75%), and four of five S. epidermidis samples were grouped according to species.
      A novel FTIR approach in classifying slime produced by S. aureus and S.
      epidermidis is reported.

PMID- 17453731
TI  - Iron dependent degradation of an isothiazolone biocide (5-chloro-2-methyl-4
      isothiazolin-3-one).
AB  - An isothiazolone biocide, 5-chloro-2-methyl-4-isothiazolin-3-one (CMI), was
      degraded in the presence of iron. According to the Fe-dependent degradation of
      CMI, stoichiometric production of chloride was observed. Copper and stainless
      steel did not enhance the physico-chemical degradation of CMI, whilst phosphate
      inhibited the Fe-dependent degradation. Neither aerobic nor anaerobic conditions
      influenced the Fe-dependent CMI degradation. Furthermore, FeO(OH)-powder and
      Fe(3)O(4)-powder did not lead to the physico-chemical degradation of CMI. Rapid
      disappearance of CMI was observed in an operating cooling water plant. CMI added
      to the cooling tower declined from 1.4 mg l(-1) to < 0.1 mg l(-1) in 2 d. This
      finding is important in optimising the use of CMI and combating resistance if
      encountered.

PMID- 17453732
TI  - Assessment of biofilm cell removal and killing and biocide efficacy using the
      microtiter plate test.
AB  - Biofilm formation on surfaces has serious economic and environmental
      implications. Growth of biofilm within a water distribution system can lead to
      problems such as biocorrosion and biofouling accumulation. To prevent and control
      these occurrences, it is necessary to use suitable biocides to remove the biofilm
      and kill biofilm cells. In this study, the genera Actinobacillus, Branhamella,
      Bacillus, Micrococcus and Acinetobacter were isolated from biofilms formed on
      brass coupons exposed to a cooling water system. It was shown by the microtiter
      plate test that a mixed culture of the isolates and a single culture of
      Acinetobacter sp(2) produced high levels of biofilm formation. A microwell plate
      technique was applied for assessment of the ability of various biocides to remove
      and kill mixed-culture biofilm cells and Acinetobacter sp(2), the latter as a
      single-species biofilm with a high rate of biofilm production. The results showed
      that the mixed-culture biofilm cells had more resistance to removal and killing
      by some biocides, such as hydrogen peroxide and sulfathiazole, than the single
      species biofilm cells (Acinetobacter sp(2)). Oxidising biocides, such as sodium
      hypochlorite and hydrogen peroxide, demonstrated a higher potential for biofilm
      removal and killing compared with non-oxidising biocides (sulfathiazole and
      glutaraldehyde).

PMID- 17453733
TI  - A review of 'green' strategies to prevent or mitigate microbiologically
      influenced corrosion.
AB  - Two approaches to control microbiologically influenced corrosion (MIC) have been
      developed that do not require the use of biocides. These strategies include the
      following: i) use of biofilms to inhibit or prevent corrosion, and ii)
      manipulation (removal or addition) of an electron acceptor, (e.g. oxygen,
      sulphate or nitrate) to influence the microbial population. In both approaches
      the composition of the microbial community is affected by small perturbations in
      the environment (e.g. temperature, nutrient concentration and flow) and the
      response of microorganisms cannot be predicted with certainty. The following
      sections will review the literature on the effectiveness of these environmentally
      friendly, "green," strategies for controlling MIC.

PMID- 17453734
TI  - Species interactions within a fouling diatom community: roles of nutrients,
      initial inoculum and competitive strategies.
AB  - Diatoms constitute an important component of the fouling community. Although a
      lot of work has dealt with the fouling diatom community structure, work on the
      species interactions within the community is still meagre. In this regard, a
      study was carried out by transferring natural diatom biofilms into controlled
      conditions in order to understand the roles of nutrients, initial cell inoculum
      and seasonal variation in species composition in structuring the fouling diatom
      community. This community exhibited seasonal variation during the monsoon, post
      monsoon and pre-monsoon periods. During each of these seasons, diatom species
      interactions varied depending upon the species composition. It was observed that
      excess nutrients favoured those species with comparatively higher growth rates,
      thereby suppressing the growth of other co-existing species. This competitive
      trait was found to be effective at an appropriate cell density ratio of the
      competitive and target species. Understanding such pathways will be useful for
      modelling the interactions between diatom species in various habitats under
      different resource conditions.

PMID- 17453735
TI  - Adhesion study of silicone coatings: the interaction of thickness, modulus and
      shear rate on adhesion force.
AB  - Interactions between coating thickness, modulus and shear rate on pseudobarnacle
      adhesion to a platinum-cured silicone coating were studied using a statistical
      experimental design. A combined design method was used for two mixture components
      and two process variables. The two mixture components, vinyl end-terminated
      polydimethylsiloxanes (V21: MW=6 kg mole(-1) and V35: MW=4 9.5 kg mole(-1),
      Gelest Inc.) were mixed at five different levels to vary the modulus. The dry
      coating thickness was varied from 160 - 740 microm and shear tests were performed
      at four different shear rates (2, 7, 12, and 22 microm s(-1)). The results of the
      statistical analysis showed that the mixture components were significant factors
      on shear stress, showing an interaction with the process variable. For the soft
      silicone coating based on the high molecular weight polydimethylsiloxane (E=0.08
      MPa), shear stress significantly increased as coating thickness decreased, while
      shear rate slightly impacted shear force especially at 160 microm coating
      thickness. As the modulus was increased (E=1.3 MPa), more force was required to
      detach the pseudobarnacle from the coatings, but thickness and rate dependence on
      shear stress became less important.

PMID- 17453736
TI  - Combinatorial materials research applied to the development of new surface
      coatings V. Application of a spinning water-jet for the semi-high throughput
      assessment of the attachment strength of marine fouling algae.
AB  - In order to facilitate a semi-high throughput approach to the evaluation of novel
      fouling-release coatings, a 'spinjet' apparatus has been constructed. The
      apparatus delivers a jet of water of controlled, variable pressure into the wells
      of 24-well plates in order to facilitate measurement of the strength of adhesion
      of algae growing on the base of the wells. Two algae, namely, sporelings (young
      plants) of the green macroalga Ulva and a diatom (Navicula), were selected as
      test organisms because of their opposing responses to silicone fouling-release
      coatings. The percentage removal of algal biofilm was positively correlated with
      the impact pressure for both organisms growing on all the coating types. Ulva
      sporelings were removed from silicone elastomers at low impact pressures in
      contrast to Navicula cells which were strongly attached to this type of coating.
      The data obtained for the 24-well plates correlated with those obtained for the
      same coatings applied to microscope slides. The data show that the 24-well plate
      format is suitable for semi-high throughput screening of the adhesion strength of
      algae.

PMID- 17453737
TI  - Antibacterial and antilarval activity of deep-sea bacteria from sediments of the
      West Pacific Ocean.
AB  - Deep-sea microorganisms are a new source of bioactive compounds. In this study,
      crude ethyl acetate extracts of 176 strains of deep-sea bacteria, isolated from
      sediments of the West Pacific Ocean, were screened for their antibacterial
      activity against four test bacterial strains isolated from marine biofilms. Of
      these, 28 deep-sea bacterial strains exhibited antibacterial activity against one
      or more of the bacteria tested. Active deep-sea bacterial strains belonged mainly
      to the genera of Pseudomonas, Psychrobacter and Halomonas. Additionally,
      antilarval activity of 56 deep-sea bacterial strains was screened using Balanus
      amphitrite larvae. Seven bacterial strains produced metabolites that had strong
      inhibitive effects on larval settlement. None of these metabolites showed
      significant toxicity. The crude extract of one deep-sea Streptomyces strain could
      completely inhibit larval settlement at a concentration of 25 microg ml(-1).

PMID- 17453738
TI  - Urinary hydroxylated metabolites of polycyclic aromatic hydrocarbons as
      biomarkers of exposure in asphalt workers.
AB  - BACKGROUND: Fumes and vapours released during laying of hot asphalt mix have been
      recognised as a major source of exposure for asphalt workers. OBJECTIVES: We
      investigated the relationships between inhalation exposure to asphalt emissions
      and urinary biomarkers of polycyclic aromatic hydrocarbons (PAHs) in asphalt
      workers (AW, n=75) and in ground construction workers (CW, n=37). METHODS: Total
      polyaromatic compounds (PAC) and 15 priority PAHs in inhaled air were measured by
      personal sampling. Hydroxylated PAH metabolites (OH-PAHs) (2-naphthol, 2
      hydroxyfluorene, 3-hydroxyphenanthrene, 1-hydroxypyrene, 6-hydroxychrysene and 3
      hydroxybenzo[a]pyrene) were determined in urine spot samples collected in three
      different times during the work week. RESULTS: Median vapour-phase PAC (5.5
      microg m(-3)), PAHs (<or=50 ng m(-3)) and OH-PAHs (0.08-1.11 microg l(-1)) were
      significantly higher in AW than in CW, except in the cases of air naphthalene and
      2-naphthol. Airborne levels of particle-phase contaminants were similar in the
      two groups and much lower than vapour-phase levels; metabolites of particulate
      PAHs were never found in quantifiable amounts. An appreciable increase in OH-PAH
      levels during the work day and work week was found in AW; median levels for 2
      hydroxyfluorene, 3-hydroxyphenanthrene and 1-hydroxypyrene were, respectively,
      0.29, 0.08 and 0.18 at baseline; 0.50, 0.18 and 0.29, pre-shift; 1.11, 0.44 and
      0.44 microg l(-1), post-shift. Each OH-PAH exhibited a characteristic profile of
      increase, reflecting differences in half-lives of the parent compounds. In non
      smoking subjects, positive correlations were found between vapour-phase PAC or
      PAHs and OH-PAHs both in pre- and post-shift samples (0.34 <or= r<or=69). Smokers
      exhibited 2-5-fold higher OH-PAHs than non-smokers, at any time and at both
      workplaces. CONCLUSIONS: Our results suggest that OH-PAHs are useful biomarkers
      for monitoring exposure to asphalt emissions. The work-related exposure to PAC
      and PAHs was low in all AW, but urinary metabolites reflected exposure
      satisfactorily.

PMID- 17453739
TI  - Vitellogenin, zona radiata protein, cathepsin D and heat shock protein 70 as
      biomarkers of exposure to xenobiotics.
AB  - The antagonistic and/or synergistic effects of different chemical compounds were
      examined in the marine teleost, Gobius niger, by testing a series of biomarkers
      involved in fish reproduction. Among the biomarkers analysed, vitellogenin (VTG)
      and zona radiata proteins (ZRP) are key molecules involved in reproduction,
      widely used to detect the presence of pollutants in the marine environment, while
      heat shock protein 70 (HSP70) and cathepsin D (CATD) have recently been
      introduced as bioindicators of endocrine disruption. The detection of VTG and ZRP
      in the plasma of wild male specimens is universally accepted as an early warning
      signal of environmental pollution. The evaluation of VTG, ZRP and CATD expression
      demonstrated the oestrogenic effect of nonylphenol on both male and female fish;
      on the contrary beta-naphthoflavone behaves mainly as an anti-oestrogen although,
      when co-injected with compounds with oestrogenic activity, it enhances ZRP gene
      expression. Regarding the chaperone, all treatments stressed the fish, inducing
      an increase in HSP70 gene transcription. The results obtained underlined the
      importance of testing the effects of compound mixtures: fish in the wild are
      subjected to a blend of chemicals and the effects observed derive from the
      synergic or antagonistic interactions of these compounds.

PMID- 17453740
TI  - Serum levels of the extracellular domain of the epidermal growth factor receptor
      in individuals exposed to arsenic in drinking water in Bangladesh.
AB  - Epidermal growth factor receptor-dependent mechanisms have been implicated in
      growth signal transduction pathways that contribute to cancer development,
      including dermal carcinogenesis. Detection of the extracellular domain of the
      epidermal growth factor receptor (EGFR ECD) in serum has been suggested as a
      potential biomarker for monitoring this effect in vivo. Arsenic is a known human
      carcinogen, producing skin and other malignancies in populations exposed through
      their drinking water. One such exposed population, which we have been studying
      for a number of years, is in Bangladesh. The purpose of this study was to examine
      the EGFR ECD as a potential biomarker of arsenic exposure and/or effect in this
      population. Levels of the EGFR ECD were determined by enzyme-linked immunosorbent
      assay in the serum samples from 574 individuals with a range of arsenic exposures
      from drinking water in the Araihazar area of Bangladesh. In multiple regression
      analysis, serum EGFR ECD was found to be positively associated with three
      different measures of arsenic exposure (well water arsenic, urinary arsenic and a
      cumulative arsenic index) at statistically significant levels (p<or=0.034), and
      this association was strongest among the individuals with arsenic-induced skin
      lesions (p <or= 0.002). When the study subjects were stratified in tertiles of
      serum EGFR ECD levels, the risk of skin lesions increased progressively for each
      increase in all three arsenic measures (also stratified in tertiles) and this
      increasing risk became more pronounced among subjects within the highest tertile
      of EGFR ECD levels. These results suggest that serum EGFR ECD levels may be a
      potential biomarker of effect of arsenic exposure and may indicate those exposed
      individuals at greatest risk for the development of arsenic-induced skin lesions.

PMID- 17453741
TI  - Biochemical markers in preclinical models of osteoporosis.
AB  - Although several treatments for osteoporosis exist, further understanding of the
      mode of action of current treatments, as well as development of novel treatments,
      are of interest. Thus, preclinical models of osteoporosis are very useful, as
      they provide the possibility for gaining knowledge about the cellular mechanisms
      underlying the disease and for studying pharmaceutical prevention or intervention
      of the disease in simple and strictly controlled systems. In this review, we
      present a comprehensive collection of studies using biochemical markers of bone
      turnover for investigation of preclinical models of osteoporosis. These range
      from pure and simple in vitro systems, such as osteoclast cultures, to ex vivo
      models, such as cultures of embryonic murine tibiae and, finally, to in vivo
      models, such as ovariectomy and orchidectomy of rats. We discuss the relevance of
      the markers in the individual models, and compare their responses to those
      observed using 'golden standard' methods.

PMID- 17453742
TI  - Potential biomarkers of an exaggerated response to endotoxemia.
AB  - Serial plasma protein analysis was used to study the acute plasma proteome
      response to endotoxemia (presence of toxic bacterial products called endotoxins
      in the blood stream). Plasma samples from healthy volunteers before and multiple
      time points up to 24 h following administration of low-dose endotoxin were
      evaluated. Plasma protein profiles were obtained by rapid extraction of whole
      plasma followed by analysis with matrix-assisted laser desorption ionisation-time
      of flight mass spectrometry. The profiles were unique to each individual and
      stable over the time of the experiment. Administration of low-dose endotoxin
      caused profound change in six of 18 individuals. At 8 h many proteins showed
      quantitative oxidation, in addition to the appearance of new components and
      disappearance of common baseline components. An exceptionally intense new
      component at 4154 mass units was identified as the activation peptide of C1
      esterase inhibitor. While recovery of baseline protein structure was nearly
      complete by 24 h, serum amyloid A, an acute-phase reactant, was still increasing
      and minor profile changes persisted. Clinical features did not distinguish these
      extreme responders from others, suggesting that plasma proteome changes offered
      unique insights into and potential biomarkers of subclinical events following
      endotoxin exposure.

PMID- 17453743
TI  - Whole genome amplification of buccal cytobrush DNA collected for molecular
      epidemiology studies.
AB  - When cytobrush buccal cell samples have been collected as a genomic DNA (gDNA)
      source for an epidemiological study, whole genome amplification (WGA) can be
      critical to maintain sufficient DNA for genotyping. We evaluated REPLI-g WGA
      using gDNA from two paired cytobrushes (cytobush 'A' kept in a cell lysis buffer,
      and 'B' dried and kept at room temperature for 3 days, and frozen until DNA
      extraction) in a pilot study (n=21), and from 144 samples collected by mail in a
      breast cancer study. WGA success was assessed as the per cent
      completion/concordance of STR/SNP genotypes. Locus amplification bias was
      assessed using quantitative PCR of 23 human loci. The pilot study showed > 98%
      completion but low genotype concordance between cytobrush wgaDNA and paired blood
      gDNA (82% and 84% for cytobrushes A and B, respectively). Substantial
      amplification bias was observed with significantly lower human gDNA amplification
      from cytobrush B than A. Using cytobrush gDNA samples from the breast cancer
      study (n =20), an independent laboratory demonstrated that increasing template
      gDNA to the REPLI-g reaction improved genotype performance for 49 SNPs; however,
      average completion and concordance remained below 90%. To reduce genotype
      misclassification when cytobrush wgaDNA is used, inclusion of paired gDNA/wgaDNA
      and/or duplicate wgaDNA samples is critical to monitor data quality.

PMID- 17453744
TI  - Development and validation of a phosphorylated SMAD ex vivo stimulation assay.
AB  - Assessing the pharmacodynamics (PD) of a potential therapeutic through the use of
      a downstream biomarker is essential. This is traditionally performed in the
      target tissue but limited volume and invasiveness of sampling pose challenges
      with solid tumours. Currently, there are several small molecule receptor kinase
      inhibitors and large molecule therapeutic antibodies in clinical trials that
      interfere with TGFbeta signalling to treat various forms of cancer. With the
      advent of these new therapies, there is a need for a surrogate tissue that is
      easily accessible and indicative of tumour response. We propose the use of an ex
      vivo TGFbeta1 stimulation of peripheral blood mononuclear cells (PBMCs) coupled
      with the measurement of phosphorylated SMAD2 (Sma/Mothers Against dpp, a
      downstream transcriptional activator) using a sandwich ELISA. TGFbeta is involved
      in many different cellular responses, such as proliferation, angiogenesis,
      migration, invasion and immunomodulation. SMAD2 and SMAD3 are phosphorylated as a
      result of the canonical cascade through ligand binding and receptor kinase
      activation. These phosphorylated SMADs (pSMAD) associate with SMAD4, a co-SMAD,
      and transcriptionally activate TGFbeta-mediated genes. This paper describes the
      novel method for measuring the downstream effects of inhibiting canonical TGFbeta
      signalling using ex vivo stimulation of surrogate tissue to predict tumour
      response. In addition, we present the assay validation rationale and data. This
      novel, validated assay can be used to gain insight into clinical trials regarding
      TGFbeta signal modulation by multiple inhibitor platforms for both large and
      small molecules.

PMID- 17453745
TI  - Documentation of endpoint prevention with combination therapy in hypertension is
      urgently needed.

PMID- 17453746
TI  - Atenolol as a comparator in outcome trials in hypertension: a correct choice in
      the past, but not for the future?
AB  - OBJECTIVE: Twelve years after the design of the Losartan Intervention For
      Endpoint reduction in hypertension (LIFE) study, which showed superiority of
      losartan- vs atenolol-based therapy for cardiovascular outcomes, we reviewed the
      literature for the effect of beta-blockers compared with initial placebo or no
      treatment on reduction of cardiovascular events to re-evaluate atenolol as the
      comparator in the LIFE study. METHODS: A literature search was conducted in
      September 2006 for randomized, controlled trials comparing beta-blockers
      with/without diuretics with placebo or no treatment in patients with hypertension
      and without recent cardiovascular morbidity. We calculated risk reductions for
      combined cardiovascular events, cardiovascular death, stroke, and coronary heart
      disease from groups of trials using atenolol first-line and all beta-blockers
      first-line. RESULTS: Five studies met the criteria. Significant risk reductions
      for cardiovascular events and stroke occurred in groups receiving treatment with
      atenolol or all beta-blockers, and for cardiovascular death in the all beta
      blocker analysis. In meta-analysis of beta-blocker vs placebo or no treatment
      trials, risk reductions were 19% for combined cardiovascular events (95% CI 0.73
      0.91, p<0.001), 15% for cardiovascular death (0.73-0.99, p = 0.037), 32% for
      stroke (0.57-0.82, p<0.001), and 10% for coronary heart disease (0.78-1.04, p =
      0.146). CONCLUSIONS: Beta-blocker-based antihypertensive therapy significantly
      reduces cardiovascular risk in hypertension compared with placebo or no
      treatment. Atenolol was an appropriate comparator in the LIFE study. As the
      results of the LIFE study and other recent trials demonstrate superiority of
      newer agents over atenolol, this agent is not an appropriate reference drug for
      future trials of cardiovascular risk in hypertension.

PMID- 17453747
TI  - Baseline characteristics in the Avoiding Cardiovascular events through
      Combination therapy in Patients Living with Systolic Hypertension (ACCOMPLISH)
      trial: a hypertensive population at high cardiovascular risk.
AB  - ACCOMPLISH is the first trial designed to compare the effects on major fatal and
      non-fatal cardiovascular endpoints of two forms of antihypertensive combination
      therapy: benazepril plus hydrochlorothiazide and amlodipine plus benazepril in
      hypertensive patients at high cardiovascular risk. Enrollment for this trial is
      now complete and this report describes the clinical characteristics of the study
      cohort. Patients with hypertension and a previous history of cardiovascular
      events, strokes or diabetes mellitus were randomized to double-blind treatment
      with either of the two combination regimens. The data in this report detail the
      clinical history and demographic characteristics in patients immediately prior to
      randomization to study drugs. A total of 11,454 patients were randomized. Mean
      age (+/-SD) was 68.4+/-6.9 years, 60% were men, and 1360 (12%) were African
      American. Mean body mass index (BMI) was 31.0+/-6.3 kg/m(2). At study entry, 46%
      of patients had a history of acute coronary syndromes, coronary artery bypass
      grafts or percutaneous coronary interventions; 13% had a history of stroke. A
      history of diabetes mellitus was reported in 6928 (60%) of patients. Mean blood
      pressure at baseline (on prior hypertension therapy) was 145.4/80.0 mmHg; only
      38% of patients had a BP less than 140/90 mmHg. Overall, 97% of patients had
      received previous antihypertensive treatment (74% on at least two drugs); 53%
      were on oral diabetes therapy or insulin, 68% on anti-lipid therapy and 63% on
      anti-platelet agents. In summary, the ACCOMPLISH trial has recruited hypertensive
      patients at high risk of cardiovascular morbidity and mortality. It is noteworthy
      that the mean BMI of 31 in this cohort is clearly above the accepted diagnostic
      criterion of obesity and that 60% of patients are diabetic, possibly reflecting
      secular trends in clinical disease.

PMID- 17453748
TI  - Metabolic syndrome, organ damage and cardiovascular disease in treated
      hypertensive patients. The ERIC-HTA study.
AB  - The aim of this study is to assess the relationship among metabolic syndrome
      (MS), target organ damage (TOD) and established cardiovascular disease (CVD) in
      non-diabetic hypertensive elderly patients. ERIC-HTA is cross-sectional,
      multicentre study carried out in primary care, on hypertensive patients aged 55
      or older. MS was defined by the NCEP-ATP III criteria, using body mass index
      (>28.8 kg/m(2)) instead of abdominal perimeter. In 8331 non-diabetic hypertensive
      patients (3663 men and 4668 women, mean age 67.7 years), the prevalence of MS was
      32.6% (men: 29.0%; women: 36.8%). A linear association was observed between a
      greater number of components of MS and a greater prevalence of left ventricle
      hypertrophy (LVH) on the electrocardiogram (p<0.001), impaired kidney function
      (p<0.001) and established CVD (p = 0.001). In a multivariate model, MS in non
      diabetic hypertensive patients was related to a greater prevalence of LVH (OR
      1.31 [95% CI: 1.15-1.48]), impaired kidney function (OR 1.45 [95% CI: 1.29-1.63])
      and established CVD (OR 1.22 [95% CI: 1.08-1.37]). This relationship persisted
      after stratifying by gender. In conclusion, in this elderly non-diabetic
      hypertensive population, the presence of MS was independently related to a
      greater prevalence of hypertensive TOD and established CVD, suggesting a role of
      MS as a cardiovascular risk marker in hypertension.

PMID- 17453749
TI  - Decreasing population blood pressure is not mediated by changes in habitual
      physical activity. Results from 15 years of follow-up.
AB  - OBJECTIVE: Population blood pressure (PBP) is the average BP shared by all
      members of a population. In PBP research, the main focus is on the great majority
      of individuals who are healthy in respect to blood pressure. From previous
      studies, we know that PBP decreased 2 mmHg during 15 years of follow-up. This
      decrease leads to significant reductions in cardiovascular (CV) and
      cerebrovascular risk. The major aim of the present study was to evaluate the
      effect of habitual physical activity on PBP. DESIGN: Copenhagen City Heart Study
      is a longitudinal epidemiological study of CV risk in a random population sample.
      Three surveys were performed with 15 years of follow-up. METHODS: BP was measured
      under standardized circumstances. A questionnaire concerning physical exercise
      was completed. Two scales were used, describing physical activity at work and
      during leisure-time, respectively. RESULTS: Most of the subjects belonged to the
      sedentary or low physical activity categories. The population did not change
      physical activity habits during the observation time. There was no significant
      difference in either systolic or diastolic BP between the categories.
      CONCLUSIONS: The previously observed reduction in PBP is not explained by a
      change in the population physical activity habits. This fact illustrates the
      difference between the high-risk strategy and the population strategy. In the
      first, the preventive strategy identifies hypertensive individuals and offers
      them antihypertensive medication and lifestyle modulation such as more and
      regular physical activity to improve blood pressure and lower individual CV and
      cerebrovascular risk. In contrast, the "population strategy" seeks to control the
      determinants of incidence in the population as a whole. This paper demonstrates
      that physical activity is not a determinant of PBP.

PMID- 17453750
TI  - Increased left ventricular mass and diastolic dysfunction are associated with
      endothelial dysfunction in normotensive offspring of subjects with essential
      hypertension.
AB  - OBJECTIVES: We aimed to investigate left ventricular (LV) morphology and function
      in normotensive offspring of subjects with essential hypertension (familial trait
      - FT), and to determine the association between LV mass and determinants of LV
      diastolic function and endothelium-dependent (NO-mediated) dilation of the
      brachial artery (BA). MATERIALS AND METHODS: The study encompassed 76 volunteers
      of whom 44 were normotonics with FT aged 28-39 (mean 33) years and 32 age-matched
      controls without FT. LV mass and LV diastolic function was measured using
      conventional echocardiography and tissue Doppler imaging (TDI). LV diastolic
      filling properties were assessed and reported as the peak E/A wave ratio, and
      peak septal annular velocities (E(m) and E(m)/A(m) ratio) on TDI. Using high
      resolution ultrasound, BA diameters at rest and during reactive hyperaemia (flow
      mediated dilation--FMD) were measured. RESULTS: In subjects with FT, the LV mass
      index was higher than in controls (92.14+/-24.02 vs 70.08+/-20.58); p<0.001).
      Offspring of hypertensive families had worse LV diastolic function than control
      subjects (lower E/A ratio, lower E(m) and E(m)/A(m) ratio; p<0.001). In subjects
      with FT, FMD was decreased compared with the controls (6.11+/-3.28% vs 10.20+/
      2.07%; p<0.001). LV mass index and E(m)/A(m) ratio were associated with FMD
      (p<0.001). CONCLUSIONS: In normotensive individuals with FT, LV morphological and
      functional changes were found. We demonstrated that an increase in LV mass and
      alterations in LV diastolic function are related to endothelial dysfunction.

PMID- 17453751
TI  - The impact of work on the night blood pressure dipping profile.
AB  - OBJECTIVE: The purpose of this study was to elucidate whether ambulatory blood
      pressure (ABPM) performed during a work day and a non-work day had any impact on
      the night dipping profile. STUDY DESIGN: A crossover randomized ABPM study in
      primary healthcare was retrospectively analysed for the occurrence of non-dipping
      (ND), dipping (D) or extreme (XD) nightly dipping. Non-dippers were defined as
      subjects with less than 10% and extreme dippers as subjects with more than 20%
      nightly blood pressure fall measured as mean arterial pressure (MAP). SUBJECTS:
      Forty treated hypertensives and 40 normotensives (20 men and 20 women in each
      group), who had performed ABPM twice in a fortnight. They had been randomly
      allocated to perform a work day or a non-work day as the first period. RESULT:
      Only one of the 16 subjects who at any time was a non-dipper remained so during
      both monitoring periods. Extreme dipping was more often reproduced in nine
      persons out of 29. Of all 80 subjects, 43.8% (35 persons) remained dippers during
      both periods. No one changed from a non-dipper to an extreme dipper or the
      reverse. The odds of being an ND were 3.8 times more common on a non-work day, p
      = 0.010. XDs were slightly more common (1.7 times) on a work day than on a non
      work day, p = 0.040. There was no correlation as to the degree of MAP and the
      dipping profile, p = 0.629. CONCLUSIONS: More subjects were non-dippers at the
      end than at the beginning of the work week. It is essential to consider this when
      attempting to identify a non-dipper by ABPM.

PMID- 17453752
TI  - Pregnancy-related factors and the risk of isolated systolic hypertension.
AB  - BACKGROUND: Isolated systolic hypertension (ISH) is known to be a strong
      predictor of cerebrovascular and cardiac events, especially in women. Metabolic
      and hormonal changes associated with reproductive history may contribute to the
      development of cardiovascular diseases. The aim of this study was to identify
      associations between pregnancy-related factors and ISH. METHODS: A cross
      sectional study based on a random sample of 3937 Finnish women aged 30-99 was
      carried out. Associations between pregnancy-related factors and ISH were analyzed
      using multivariate analyses. RESULTS: Of 3470 subjects, 26% had ISH. Younger age
      at first delivery predicted a higher risk of ISH (odds ratio after adjustment for
      age, education, smoking, height and weight = 1.31, 95% CI 1.07-1.61). Age at
      first and last delivery was significantly associated with age, education, marital
      status and use at any time of hormone replacement therapy (HRT); age at first
      delivery was also associated with toxemia in any pregnancy, weight and body mass
      index (BMI). In the univariate analyses, ISH was significantly associated with
      age, height, weight, BMI, education, marital status, oral contraceptive pills use
      at any time and HRT use at any time. CONCLUSION: This population-based study
      showed that early age at first delivery increased the risk of ISH, which may in
      turn increase cerebrovascular and cardiac events after menopause. Age at first
      delivery is heavily dependent on education, which may be linked to the risk of
      developing of cardiovascular disease throughout adulthood. The other plausible
      mechanism may be adiposity due to pregnancy.

PMID- 17453753
TI  - Association of pulse pressure with carotid atherosclerosis in patients with type
      2 diabetes mellitus.
AB  - Pulse pressure is known to be a potent risk factor for cardiovascular disease.
      However, it has not been determined whether pulse pressure is associated with
      cerebrovascular disease in patients with diabetes mellitus. The purpose of the
      present study was to investigate association of pulse pressure with carotid
      atherosclerosis in patients with diabetes and to determine whether age and gender
      affect the association. A cross-sectional study was performed using outpatients
      with type 2 diabetes. Carotid atherosclerosis and arterial stiffness were
      evaluated by intima-media thickness of common carotid arteries (IMT) and aortic
      pulse wave velocity (a-PWV), respectively. The relationship of brachial pulse
      pressure with IMT was analyzed. Pulse pressure was significantly correlated with
      age, duration of diabetes, systolic blood pressure, serum sialic acid, a-PWV and
      IMT. The mean IMT in the highest tertile group of pulse pressure after adjustment
      for gender was significantly higher than the mean IMT in the lowest tertile
      group. In analysis using subgroups of gender, a significant correlation between
      pulse pressure and IMT was shown in women but not in men. In multiple regression
      analysis, there was a significant correlation between pulse pressure and IMT in
      women independently of age, body mass index, systolic blood pressure, hemoglobin
      A1c, atherogenic index, a-PWV, history of therapy for hypertension and history of
      nephropathy. The results of this study suggest that pulse pressure is a major age
      independent predictor of carotid atherosclerosis in female patients with
      diabetes.

PMID- 17453754
TI  - A review of pharmacological treatments used in experimental models of traumatic
      brain injury.
AB  - PRIMARY OBJECTIVE: We provide a review of recent chronic and delayed
      rehabilitative pharmacological treatments examined in experimental models of
      traumatic brain injury. There is a specific emphasis on studies aiming to enhance
      cognitive recovery. MAIN OUTCOMES AND RESULTS: Decreased neuronal activity is
      believed to contribute to persistent cognitive disabilities. Neurotransmitter
      based rehabilitative treatments that increase neuronal activity may assist in the
      recovery of cognitive function. However, timing and dosage of drug treatment are
      influential in cognitive enhancement. Drug treatments that affect single and
      multiple neurotransmitter systems have the ability to significantly influence
      recovery of function following brain injury. CONCLUSIONS: Understanding the
      relationship between neural disturbances and functional deficits following brain
      injury is challenging. Cognitive impairment may be the result of a single event
      or multiple events that occur after the initial insult. Increasing neuronal
      activity during the chronic phase of injury seems to be an effective treatment
      strategy for facilitating cognitive recovery. Pharmacological agents do not
      necessarily display the same effects in an injured brain as in a non-injured
      brain. Thus, further research is needed to establish the effectiveness of
      rehabilitative drug treatments.

PMID- 17453755
TI  - Transplantation of neural stem cells into the traumatized brain induces
      lymphocyte infiltration.
AB  - OBJECTIVE: This study examined the lymphocyte infiltration induced by neural stem
      cell grafts in the traumatized brain. METHODS: Sixty Sprague-Dawley rats were
      assigned randomly to transplantation (n = 30) or control (n = 30) groups, and
      each rat was subjected to brain contusion. The neural stem cells derived from
      Wistar rats were transplanted into the lesion of the transplantation group, and
      saline was injected instead into the controls. Local lymphocyte infiltration was
      studied using haematoxylin and eosin staining, immunohistochemistry and flow
      cytometry. The immunogenicity of neural stem cells was evaluated using MHC-I
      expression. RESULTS: About 6.57 +/- 0.44% of the neural stem cells expressed MHC
      I. In the transplantation group, histological examination and
      immunohistochemistry revealed significant lymphocyte infiltration in the
      contusion. The ratio of CD4(+) lymphocytes to total cells in the lesions was
      13.28 +/- 1.60% in the transplantation group and 0.41 +/- 0.12% in the controls
      (p < 0.01). Likewise, the ratio of CD8(+) lymphocytes to total cells was 5.11 +/-
      1.03% in the transplantation group and 0.57 +/- 0.26% in the controls (p < 0.01).
      CONCLUSIONS: Neural stem cells possess immunogenicity and can induce lymphocyte
      infiltration when transplanted into a traumatised brain. Our findings imply that
      immunosuppressive treatment is necessary following neural stem cell
      transplantation.

PMID- 17453756
TI  - Do lesion site and severity predict deficits in attentional control after
      preschool traumatic brain injury (TBI)?
AB  - PRIMARY OBJECTIVE: To determine the predictive value of structural neuroimaging
      in the clinical setting following TBI. RESEARCH DESIGN: Prospective between-group
      design, comparing groups with regard to: (i) the presence or absence of cerebral
      pathology and (ii) the location of cerebral pathology. The predictive value of
      injury variables was investigated using hierarchical regressions. METHODS AND
      PROCEDURES: Thirty-six children, between 6 and 14 years, who sustained a moderate
      to severe TBI 5 years previously participated in this study. Children's
      performances on five measures of attentional control were examined in relation to
      the presence, location and severity of their lesions, as coded by the Coffey
      classification system 1. MAIN OUTCOMES AND RESULTS: Frontal lesion severity was
      not predictive of performance on any of the measures. However, generalized
      (frontal and extrafrontal) and extrafrontal lesion severity was predictive of
      poor performance. CONCLUSIONS: These findings support the argument that
      functional organization in children may differ from that in adults, suggesting
      that multiple cerebral regions, or a diffuse cerebral network, may mediate
      children's executive functions (EF). Results are also consistent with the
      hypothesis that the amount of damaged brain tissue, rather than its location, may
      be more predictive of neurobehavioural outcome following early TBI.

PMID- 17453757
TI  - Case ascertainment in pediatric traumatic brain injury: challenges in using the
      NEISS.
AB  - PRIMARY OBJECTIVE: To evaluate mild traumatic brain injury (TBI) case
      ascertainment in the US National Electronic Injury Surveillance System (NEISS).
      RESEARCH DESIGN: A sample of NEISS injury cases was analyzed. Two trained
      researchers independently reviewed diagnostic codes based on the International
      Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). The
      sensitivity and specificity of two NEISS TBI definitions were evaluated, and
      Kappa coefficients were calculated to evaluate the agreement between NEISS TBI
      definitions and the standard TBI definition based on the ICD-9-CM. RESULTS: Our
      sampling procedures provided a total of 1,018 NEISS cases, of which 880 were
      injury cases and 138 were non-injury cases. Out of the injury cases, 54 cases
      were defined as mild TBI cases based on the ICD-9-CM diagnosis codes. Compared
      with non-TBI injury cases, a significantly higher percentage of TBI cases (33.3%
      versus 15.4%) were infants less than 1 year old and TBI cases were more likely to
      be admitted for hospitalization. If TBI was identified using NEISS definition 1
      (diagnosis code 52 for 'concussion'), the sensitivity was only 38.9% (95%
      confidence intervals (CI) = 25.9-51.9%). However, if TBI was identified using
      NEISS definition 2 (diagnosis code 52 for 'concussion' or 62 for 'internal organ
      injury' and 'head' was the affected body part), the sensitivity increased
      dramatically to 79.6% (95% CI = 68.9-90.4%). The Kappa coefficient for overall
      agreement between the NEISS and ICD-9-CM system was 0.528 (95% CI = 0.393-0.664)
      for NEISS definition 1 and 0.807 (95% CI = 0.723-0.892) for NEISS definition 2.
      CONCLUSIONS: The current approach of pediatric TBI case ascertainment in the
      NEISS faces some challenges in identifying mild TBI. Future research efforts are
      needed to refine TBI case ascertainment in the NEISS.

PMID- 17453758
TI  - Neuropsychiatric consequences of traumatic brain injury: a comparison between two
      age groups.
AB  - BACKGROUND: Neurobehavioural symptoms and certain psychiatric disorders are
      common after a traumatic brain injury (TBI). Relatively few studies have
      investigated the effect of age upon these outcomes. AIM: Our aim was to compare
      the rates of neurobehavioural symptoms and psychiatric disorders between 18-65
      year old and over 65 year old patients with TBI. METHOD: 120 adults aged 18 to 65
      years and 45 adults over 65 years of age who were admitted to a hospital
      following a TBI were assessed for neurobehavioural symptoms and psychiatric
      disorders one year after the injury. RESULTS: Our estimate suggested that a
      higher proportion of 18-65 year old patients (32%) had ICD-10 psychiatric
      disorders according to the Schedule for Clinical Assessment in Neuropsychiatry
      (SCAN) interview compared with patients over 65 years of age (16%). Similarly,
      the ICD-10 depressive disorder was more common among the younger patients (16%)
      than the older group of patients (11%). None of these differences were
      statistically significant. However, a multiple regression analysis revealed that
      among other risk factors, a younger age was significantly associated with the
      presence of a psychiatric disorder. Also, a significantly higher rate of
      psychiatric caseness was detected among the younger age group using screening
      instruments such as the General Health Questionniare-28 (GHQ-28) (p < 0.01) and
      the Clinical Interview Schedule-Revised (CIS-R) (p < 0.01). The rates of
      individual neurobehavioural symptoms varied significantly between the two age
      groups. The most prevalent symptoms in 18-65 year olds were irritability (37%)
      and sleep problems (37%). In the older group of patients the most prevalent
      symptoms were poor memory (40%), dependence (38%) and slowness in thinking (33%).
      CONCLUSION: 18-65 year old patients are likely to be at a greater risk of
      psychiatric morbidity following TBI than over 65 year olds whereas
      neurobehavioural symptoms are prevalent in both age groups.

PMID- 17453759
TI  - Cognitive performance after mild traumatic brain injury: the impact of poor
      effort on test results and its relation to distress, personality and litigation.
AB  - PRIMARY OBJECTIVE: To compare consecutive Mild Traumatic Brain Injury (MTBI)
      patients with and without adequate effort on cognitive performance, litigation
      status, fatigue, distress and personality. RESEARCH DESIGN: (Neuro)psychological
      assessment was done 6 months post-injury in 110 patients from a cohort of 618
      consecutive MTBI patients aged 18-60, who attended the emergency department of
      our level I trauma centre. Effort was tested with the Amsterdam Short Term Memory
      test. MAIN OUTCOME AND RESULTS: Thirty patients (27%) failed the effort test.
      Poor effort was associated with significantly poorer scores on seven out of
      eleven measures, covering all tested domains. Poor effort was associated with
      lower educational level and changes in work status, but not litigation.
      Furthermore, poor effort was related to high levels of distress, Type-D
      personality and fatigue. CONCLUSIONS: Even in a sample of non-referred MTBI
      patients, poor effort was common and was strongly associated with inferior test
      performance. These findings imply that effort testing should be part of all
      cognitive assessments, also outside mediolegal settings. Behavioural factors like
      distress and personality should be considered as potential threats to the
      validity of neuropsychological testing after MTBI.

PMID- 17453760
TI  - Correlates of invalid neuropsychological test performance after traumatic brain
      injury.
AB  - PRIMARY OBJECTIVE: To investigate external correlates of invalid test performance
      after traumatic brain injury, as assessed by the California Verbal Learning Test 
      Second Edition (CVLT-II) and Word Memory Test (WMT). RESEARCH DESIGN:
      Consecutive 2-year series of rehabilitation referrals with a diagnosis of
      traumatic brain injury (n = 87). METHODS AND PROCEDURES: Logistic regression
      analysis was used to determine which demographic and neurological variables best
      differentiated those with vs. without actuarial CVLT-II or WMT evidence for
      invalid responding. MAIN OUTCOMES AND RESULTS: Twenty-one participants (about
      24%) performed in the invalid range. The combination of a premorbid psychiatric
      history with minimal or no coma was associated with an approximately four-fold
      increase in the likelihood of invalid performance. CONCLUSIONS: Premorbid
      psychosocial complicating factors constitute a significant threat to validity of
      neuropsychological test results after (especially mild) traumatic brain injury.
      At the same time, care should be taken to not routinely assume that all persons
      with mild traumatic brain injury and premorbid psychiatric histories are simply
      malingering. The WMT appears to be a promising instrument for the purpose of
      identifying those cases where neuropsychological test results are confounded by
      factors not directly related to acquired cerebral impairment.

PMID- 17453761
TI  - Can measures of cognitive function predict locomotor behaviour in complex
      environments following a traumatic brain injury?
AB  - PRIMARY OBJECTIVE: To determine the relationships between clinical measures of
      executive function and attention, and laboratory measures of anticipatory
      locomotor adaptations with dual tasks following a TBI. METHODS AND PROCEDURES:
      Ten people with moderate or severe TBI were compared to 10 healthy subjects for
      neuropsychological measures in the clinic, as well as locomotor patterns and
      reading time in the laboratory for adapted Stroop tasks (Bar and Word) during
      unobstructed and obstructed walking. MAIN OUTCOMES AND RESULTS: As previously
      found 1 (Vallee M, McFadyen BJ, Swaine B, Doyon J, Cantin JF, Dumas D. Effects of
      environmental demands on locomotion after traumatic brain injury. Archives of
      Physical Medicine Rehabilitation 2006;87:806--813) during the locomotor
      activities, subjects with TBI walked slower, had higher clearance margins and
      took longer to read during the Stroop tasks than healthy subjects. In general,
      subjects with TBI also showed deficits in executive functions and attention.
      Significant relationships were specifically observed between scores on Trail
      Making B and clearance margins for subjects with TBI, but not for healthy
      subjects. Alternatively, significant relationships between clinical scores on
      Stroop and dual task Stroop reading times were obtained for healthy subjects but
      not for subjects with TBI. CONCLUSIONS: These results suggest that measures of
      executive functioning and attention may be associated to locomotor behaviour in
      complex environments following a moderate to severe TBI.

PMID- 17453762
TI  - Intrathecal baclofen therapy for spastic hypertonia in chronic traumatic brain
      injury.
AB  - OBJECTIVE: To describe the outcome of intrathecal baclofen (ITB) therapy in
      treating spastic hypertonia and its sequelae in individuals with chronic (>14
      years) traumatic brain injuries (TBI). DESIGN: Case series. SETTING: Free
      standing rehabilitation hospital. PARTICIPANTS: Three adult males who received a
      TBI 14, 17.1, and 19.9 years prior to receiving ITB pump. OUTCOME MEASURES:
      Modified Ashworth Scale (MAS); Functional Independence Measure (FIM)-mobility
      scores; and informal functional evaluation. INTERVENTION: ITB therapy. RESULTS:
      MAS scores of the five most hypertonic muscles in the affected lower limbs
      improved following of ITB therapy. FIM-mobility scores did not change from
      baseline, but certain functional domains improved, such as gait, transfers, and
      sitting; decreased assistance for activities of daily living (ADL) and nursing
      care; decreased painful spasms; and increased community mobility and
      participation in recreational activities. CONCLUSION: ITB therapy is still
      beneficial even >14 years after TBI onset. In spite of the absence of improvement
      in FIM scores, functional enhancements in areas not measured by traditional
      scales can still be achieved. This suggests that in this patient population
      consideration for ITB therapy should not be based solely on conventional
      assessment scales.

PMID- 17453763
TI  - Recurrent fever in patient in a minimally responsive state: An unusual origin of
      infection.
AB  - Embolization of a severed tube of a ventriculo-atrial shunt into the heart is a
      rare but severe and potentially lethal complication of aresorptive hydrocephalus
      therapy in patients with severe neurological damage. A rare case is presented of
      a 53-year-old woman who suffered a severe subarachnoidal haemorrhage. After
      infection of the first shunting system, the patient underwent an exchange of the
      system, but repeatedly showed clinical and laboratory signs of infection which
      failed to improve despite several antibiotic treatments. This case illustrates
      that, although the patient was in poor neurological and medical condition, it is
      beneficial to remove the accidentally washed-in foreign body for two reasons. On
      the one hand to prevent avoidable life-threatening incidents, on the other hand
      to gain stable medical condition which will allow the patient to participate in
      neurorehabilitative treatment.

PMID- 17453765
TI  - How much can be concluded from the International Subarachnoid Aneurysm Trial
      (ISAT)?
AB  - Recently published data from the International Subarachnoid Aneurysm Trial (ISAT)
      shows that for patients enrolled in the trial there is a 7.4% reduction in the
      incidence of death or dependency at 1 year if they undergo coiling, rather than
      clipping. Furthermore, extrapolation of longer-term follow-up data for patient
      mortality appears to suggest that this advantage will be maintained in the longer
      term. Based on a reassessment of the published data, the authors note: (1) the
      incidence of rebleeding following treatment is approximately three times higher
      in the coiled group (p<0.001); (2) the need for aneurysm retreatment is likely to
      be higher in the coiled group; (3) trends in longer-term mortality data are not a
      reliable basis for predicting future outcomes of the trial; (4) trends in longer
      term morbidity data are more reliable and suggest that the advantage of coiling
      diminishes with time; (5) The absence of up-to-date published rates of aneurysm
      retreatment and of longer-term rates of death or dependence makes ISAT extremely
      hard to interpret. It is far from clear that the early advantage of coiling will
      be maintained in the future and, hence, longer follow-up is required. Treatment
      of aneurysms is a continually evolving field and there is currently no other
      major source of information concerning management of aneurysms. For these reasons
      the authors recommend the instigation of a national aneurysm registry to
      prospectively collect data.

PMID- 17453766
TI  - ISAT: Will the results stand the test of time?

PMID- 17453767
TI  - How much can be concluded from ISAT?

PMID- 17453768
TI  - Transfer times for patients with extradural and subdural haematomas to
      neurosurgery in Greater Manchester.
AB  - Delay in transfer of patients with acute extradural (EDH) or subdural (SDH)
      haematoma to definitive neurosurgical evacuation has a detrimental effect on
      outcome. From July 2003 to December 2005 we undertook a prospective analysis of
      patients admitted to our unit for neurosurgical evacuation of their haematoma,
      who were transferred from non-neurosurgical hospitals. Data was collected for: 1)
      overall transfer time, 2) time taken from injury or deterioration to CT scan, 3)
      time from CT scan to arrival at our unit, and 4) time from arrival at our unit to
      surgery. Overall 81 patients were eligible, of which 39 had an EDH and 42 a SDH.
      The median transfer times for EDH and SDH were 5.25 hours and 6.0 hours
      respectively. This paper discusses the factors that may prolong delays in the
      transfer of patients between hospitals and the way in which our unit is trying to
      improve the local service for the population of Greater Manchester.

PMID- 17453769
TI  - Acute extradural haematoma in the elderly.
AB  - The world's population of persons over 65 years of age (elderly) is increasing.
      Acute extradural haematoma (AEDH) in the elderly is rare. There has not been a
      publication dedicated solely to the evaluation of AEDH in the elderly. We
      undertook this study in order to establish a clinical profile in this important
      subgroup. It took the form of a retrospective evaluation of the in-patient charts
      of elderly patients with AEDH, performed over a 23-year period (1983-2005) at a
      single institution. Of 3249 patients with AEDH, 32 (<1%) were defined as elderly.
      Assault was the commonest causative factor (56%), followed by falls (25%) and
      motor vehicle accidents (19%). Eight patients died (25% mortality). Only a third
      of patients, (34%) made a good outcome, the majority of these were assault
      victims. No patient in coma, or over 75 years made a good outcome. The prognosis
      of elderly patients with AEDH is poor. Conservative treatment for comatose
      patients and the over 75s is justified.

PMID- 17453770
TI  - The reproducibility of transcranial Doppler middle cerebral artery velocity
      measurements: implications for clinical practice.
AB  - Use of transcranial Doppler (TCD) to diagnose vasospasm has been criticised. We
      examined reproducibility of TCD middle cerebral artery (MCA) velocity
      measurements. Thirty-six healthy adult volunteers were recruited. Four operators,
      two experienced and two inexperienced, participated. MCA velocity was measured
      twice by one operator and once by a second operator. Mean (95% limits of
      agreement) interoperator agreement was 2.4(+/-36.7) cm/s. Experienced vs.
      inexperienced, inexperienced vs. inexperienced, and experienced vs. experienced
      operators were -2.8(+/-39.3), -5.6(+/-40.1), 1.8(+/-22.1) cm/s, respectively.
      Intraoperator agreement across all operators, experienced and inexperienced were 
      0.5(+/-16.9), -1.6(+/-19.3), 0.7(+/-13.7) cm/s, respectively. Interoperator
      limits of agreement for experienced operators were almost half that of
      inexperienced operators. Intraoperator reproducibility was much better,
      regardless of level of experience, but aberrant results did occur even with
      experienced operators. If TCD measurements are used to guide management it is
      essential that operators are adequately trained, and readings repeated before
      potentially harmful treatments are instituted.

PMID- 17453771
TI  - Total thoracic vertebrectomy with anterior and posterior column reconstruction
      via single posterior approach.
AB  - We present two cases of vertebral body tumours presenting with neurological
      compromise treated with posterior approach vertebrectomy and three-column
      reconstruction using in situ expandable cage and pedicle screw reconstruction.
      One was performed in a staged procedure, the second as a single procedure. This
      approach avoids the requirement, and associated comorbidity, of combined anterior
      and posterior approaches. Although previously described as appropriate to
      minimize comorbidity in patients with metastatic spinal disease, we believe this
      strategy should be considered in any patient requiring three-column resection and
      stabilization in the thoracic spine.

PMID- 17453772
TI  - Thoracic intradural disc herniation.
AB  - Intradural disc herniation is a well-recognized entity in the lumbar region,
      where over 90% of all intradural herniations are seen.1 By contrast, fewer than
      5% occur in either the cervical or thoracic regions.1 We describe a case of a
      sudden onset neurological deficit caused by an intradural thoracic disc
      herniation at the T11-T12 level, the intradural nature of which was not diagnosed
      on preoperative MRI. To the best of our knowledge this is the first description
      of an intradural disc herniation at this level.

PMID- 17453773
TI  - Contiguous synchronous occurrence of primary cerebral lymphoma and meningioma.
AB  - An unusual combination of primary cerebral lymphoma and meningioma occurring
      contiguously was encountered in a 71-year-old male patient. The possibility of
      two separate tumours was suspected radiologically and confirmed by histology. The
      association of primary lymphoma and meningioma is extremely rare. Following
      review of the literature, current evidence would suggest that the association is
      probably coincidental.

PMID- 17453774
TI  - Intradural extramedullary primary malignant melanoma radiographically mimicking a
      neurofibroma.
AB  - A case of intradural extramedullary primary malignant melanoma mimicking the
      presentation of a neurofibroma is described. We emphasise the fact that surgeons
      should be aware of unexpected malignant lesions involving spinal nerve roots.

PMID- 17453775
TI  - In vivo alteration of Strata valve setting by vagus nerve stimulator-activating
      magnet.
AB  - We report the unexpected adjustment of a Strata shunt valve by a vagus nerve
      stimulator-activating magnet, resulting in symptomatic under-drainage of CSF.
      Implantable devices using magnets for calibration and activation are becoming
      more prevalent within neurosurgery and the present case highlights the potential
      for adverse interactions.

PMID- 17453776
TI  - An unusual stab wound of the cervical spine caused by a casuarina stick.

PMID- 17453777
TI  - A rare cause of cervical cord compression.

PMID- 17453778
TI  - Pituicytoma: a misdiagnosed benign tumour of the posterior pituitary.

PMID- 17453781
TI  - Antibiotic prophylaxis in patients undergoing clean, non-implant craniotomy.

PMID- 17453785
TI  - Challenges to neurosurgery service delivery. Who moved my cheese?
AB  - The change programme in the National Health Service has moved the Acute Trusts
      providing neurosurgical services to very different ways of delivering healthcare.
      The process of reform has been supported by investment but the next few years
      will see far less additional money, and success and failure of services will be
      dependent upon the approach to those reforms. The 'payment by results' system of
      funding through tariff, the 'plurality of providers' policy of forcing
      commissioners to purchase activity from independent providers, the 'patient
      choice' process of encouraging patients to select treatment from a number of
      providers, and the '18-week wait' target of bringing down referral to treatment
      times are all major shifts in the way services are delivered and developed. The
      reforms have not been made with neurosurgery in mind, how will they affect the
      way this small specialty is delivered?

PMID- 17453786
TI  - "Challenges to neurosurgical service delivery".

PMID- 17453787
TI  - Hugh Cairns and the origin of British neurosurgery.
AB  - Sir Hugh Cairns, the first Nuffield Professor of Surgery in Oxford and consultant
      neurosurgeon to the Royal Army Medical Corps during World War II, was a leader in
      helping to establish neurosurgery as a speciality in Britain. After learning the
      craft from Dr Harvey Cushing in Boston, Cairns fought against the general
      surgical orthodoxy in London to establish the first specialised neurosurgical
      unit in a teaching hospital. We review his early life, training with Cushing, his
      inspiring character and administrative prowess which not only helped to win the
      battle for neurosurgery in London but also helped to establish the Oxford
      Clinical School and to save thousands of lives during the Second World War.

PMID- 17453788
TI  - Variability of the subthalamic nucleus: the case for direct MRI guided targeting.
AB  - Because of concerns about direct visualization of the subthalamic nucleus (STN)
      on magnetic resonance imaging (MRI), many functional neurosurgeons continue to
      rely on atlas-based coordinates to reach this target. T2-weighted MRI does allow
      direct visualisation of the STN. In order to compare the coordinates of the
      target point within the visualised STN with those obtained from standard brain
      atlases, the preoperative stereotactic T2-weighted MRI used to implant 55 deep
      brain stimulation electrodes in the visualised STN of 29 consecutive patients
      with Parkinson's disease treated in two European centres were studied. The
      coordinates of the directly visualised STN were significantly different from
      those of the atlas target. Variability of the position of the STN may render
      direct visualisation a more accurate means of targeting this nucleus.

PMID- 17453789
TI  - Cauda equina syndrome: what is the correlation between clinical assessment and
      MRI scanning?
AB  - The indications for magnetic resonance imaging (MRI) in suspected cauda equina
      syndrome, and the urgency for this investigation are regularly disputed. In this
      study we assess the ability of neurosurgical residents to predict on clinical
      grounds in which patients with cauda equina syndrome (CES) this was due to
      prolapsed intervertebral disc thereby justifying a request for urgent MR imaging.
      DESIGN: Prospective cohort study of all adult patients with a suspected diagnosis
      of cauda equina syndrome. SETTING: A single tertiary referral neurosurgical
      centre. PARTICIPANTS: All patients referred over a four month period with a
      suspected diagnosis of cauda equina syndrome. RESULTS: MRI was normal in 10 (43%)
      patients. A disc prolapse causing cauda equina distortion was present in 5 (22%)
      patients. The diagnostic accuracy of urinary retention, urinary frequency,
      urinary incontinence, altered urinary sensation and altered perineal sensation
      were 0.57, 0.65, 0.61 ,0.65 and 0.60 respectively. CONCLUSIONS: Because it is
      impossible in a significant proportion of patients to exclude the diagnosis of
      prolapsed intervertebral disc in the context of referral with suspected cauda
      equina compromise the authors recommend urgent MRI assessment in all patients who
      present with new onset urinary symptoms in the context of lumbar back pain or
      sciatica.

PMID- 17453791
TI  - Hypopituitarism following traumatic brain injury (TBI).
AB  - Traumatic brain injury (TBI) is the commonest cause of death and disability in
      young adults living in industrialised countries. Recently, several studies have
      shown that hypopituitarism is a common complication of head trauma, with a
      prevalence of at least 25% among patients who were studied months or years
      following injury. This remarkably high frequency has changed the traditional
      concept of hypopituitarism being a rare complication of TBI, and suggests that
      most cases of posttraumatic hypopituitarism remain undiagnosed and untreated in
      clinical practice. It is therefore reasonable to infer that posttraumatic
      hypopituitarism may have an important contribution to the high physical and
      neuropsychiatric morbidity seen in patients with head injury. This article
      discusses the published reports on neuroendocrine dysfunction in TBI patients and
      the natural history of this disorder. The potential impact of posttraumatic
      hypopituitarism on recovery and rehabilitation after injury will also be
      examined, as well as the need for the identification, and appropriate and timely
      management of hormone deficiencies in order to reduce morbidity, aid recovery,
      and avoid the long-term complications of pituitary failure.

PMID- 17453790
TI  - Detection of cathepsin S cysteine protease in human brain tumour microdialysates
      in vivo.
AB  - Microdialysis enables the chemistry of extracellular fluid in body tissues to be
      measured. Extracellular proteases such as the cysteine protease, cathepsin S
      (CatS), are thought to facilitate astrocytoma invasion. Microdialysates obtained
      from human brain tumours in vivo were subjected to cathepsin S activity and ELISA
      assays. Cathepsin S ELISA expression was detected in five out of 10 tumour
      microdialysates, while activity was detected in five out of 11 tumour
      microdialysates. Cathepsin S expression was also detected in microdialysate from
      the normal brain control although no activity was found in the same sample. While
      some refinements to the technique are necessary, the authors demonstrate the
      feasibility and safety of microdialysis in human astrocytomas in vivo.
      Characterisation of the extracellular environment of brain tumours in vivo using
      microdialysis may be a useful tool to identify the protease profile of brain
      tumours.

PMID- 17453792
TI  - Cerebellar developmental venous anomalies with associated vascular pathology.
AB  - Cerebellar developmental venous anomalies (CDVA) are benign conditions, although
      sometimes they are associated with haemorrhages and reported to be symptomatic.
      This is the largest follow-up study to investigate the symptomatology of CDVAs
      and their association with other malformations. Thirty-two patients were followed
      for 2 - 9 years. Twenty-eight had isolated asymptomatic CDVA without any
      neurological condition during follow-up, which might be linked to the CDVA. Four
      patients had CDVA and an associated vascular pathology: two pontine cavernomas,
      one asymptomatic arteriovenous malformation (this is the first published case in
      the literature) and one cerebellar infarct with a developmental variation of the
      posterior fossa venous circulation. One patient had two CDVAs, while another had
      a unique draining vein from the upper part of the brainstem too. In conclusion,
      CDVAs are benign, asymptomatic conditions, but they are sometimes associated with
      pathogenic malformations requiring detailed neuroradiological investigations.

PMID- 17453793
TI  - The radiographic evolution of a Schmorl's node.
AB  - We present a case showing the development of a Schmorl's node from its acute to
      chronic stage by serial MRI. In contrast to the mature Schmorl's node, imaging
      characteristics of the acute Schmorl's node have not been well-illustrated,
      particularly by contrast-enhanced images at various stages of development.

PMID- 17453794
TI  - Spinal Langerhans' cell histiocytosis in a young adult: case report and
      therapeutic considerations.
AB  - We report an unusual case of spinal Langerhans' cell histiocytosis of the
      cervicothoracic junction in a young adult man. A 17-year-old male was referred to
      our institution with a 3-week history of cervicothoracic pain associated to a
      weakness of his right upper limb. Computed tomography and magnetic resonance
      imaging showed a collapsed T1 vertebral body with epidural soft tissue showing
      mass effect on spinal cord. The patient underwent a classic anterior cervicotomy.
      Complete removal of the lesion could be achieved, but the soft consistency of C7
      and T2 body precluded a solid anterior fixation and an extended resection of C7
      and T2 body had to be performed. Then a C6 - T3 stabilisation using an anterior
      plate fixation and cyanomethylacrylate graft was performed. Postoperative course
      was uneventful. At 2 years follow-up, the patient was asymptomatic and
      radiological workup showed a perfect stability of anterior fixation system.
      Aggressive surgical management of eosinophilic granuloma should be considered in
      some selected cases particularly when spinal instability or neurological deficit
      occurs. In this young patient a modified anterior cervicotomy allowed a
      comfortable approach to the anterior aspect of T3 vertebra for spinal fixation.

PMID- 17453795
TI  - A diagnostic dilemma: cervical myelopathy in the presence of chiari 1
      malformation and multi-level cord compression in a 79-year-old woman.
AB  - Chiari 1 malformation (CM1) is an unusual finding in the elderly population.
      Presenting features can overlap with other conditions including cervical
      spondylotic myelopathy (CSM); a more prevalent pathology in this age group. We
      present a rare case of CM1 in a 79-year-old woman with concomitant CSM who made
      an excellent recovery following a combined foremen magnum decompression and C5
      skip laminectomy.

PMID- 17453796
TI  - Jejunal perforation and peroral extrusion of a peritoneal shunt catheter.

PMID- 17453797
TI  - Traumatic callosomarginal aneurysm following orbital gunshot wound in a 16-year
      old girl.

PMID- 17453801
TI  - Daytime behavioural patterns of slow-growing chickens in deep-litter pens with
      perches.
AB  - 1. Behavioural patterns of 4 slow-growing local breeds of chickens in Taiwan and
      China, Taiwan Country chickens, Beijing Fatty chickens, pure Silkies, and
      upgraded commercial Silkies, were studied from 5 to 16 weeks of age as a
      reference of management for commercial production. 2. Fifteen males and 15
      females of the same breed were housed in a pen. Every breed had 6 pens and 24
      pens were studied. 3. Taiwan Country chickens displayed more aggressive, sexual
      and feather pecking behaviours, had less resting time, the fastest feeding rate
      and used perches more often. The fast-growing and heavy commercial Silkies had
      more feeding activity and less preening activity. They were also similar to the
      crested and docile Beijing Fatty chickens and had less stand/walking and more
      resting time. The pure Silky bantams showed much more foraging activity than the
      other breeds. 4. When males started to display more aggression and sexual
      behaviour, after 8-12 weeks of age, resting time for all birds started to decline
      and stand/walking increased. 5. These results could imply that different local
      breeds need different housing systems for the bird's welfare.

PMID- 17453802
TI  - Effect of soft X-ray irradiation on the migratory ability of primordial germ
      cells in chickens.
AB  - 1. The present study was conducted to elucidate the effect of soft X-ray
      irradiation on the migratory ability of primordial germ cells (PGCs) to the
      germinal ridges of chicken embryos. 2. PGCs (Barred Plymouth Rock, BPR) were
      isolated from embryonic blood and irradiated with soft X-rays for 1-10 min. Then,
      the PGCs were transfected in vitro with GFP gene by lipofection. The manipulated
      PGCs were transferred to recipient embryos (White Leghorn, WL) and migration to
      the germinal ridges was analysed by examining GFP gene expression in the gonads
      of recipient embryos under UV light at x40 magnifications. The expression of GFP
      gene was detected in all the gonads of recipient embryos examined up to 10.5 d of
      culture. 3. Migration of PGCs irradiated with soft X-rays to the germinal ridges
      was also confirmed by detecting a single nucleotide polymorphism in the D-loop
      region of the mitochondrial DNA of BPR and WL chickens. Freshly collected PGCs
      (BPR) were transferred to the bloodstream of recipient embryos (WL). The fate of
      the transferred donor PGCs was traced by detecting the single nucleotide
      polymorphism in the D-loop region of the mitochondrial DNA in BPR and WL used in
      this study. Transferred donor PGC-derived cells were detected in all the gonads
      of 17-d cultured embryos by PCR. 4. The results suggest that PGCs irradiated with
      soft X-rays still retain the ability to migrate to the germinal ridges of
      recipient embryos.

PMID- 17453803
TI  - Frequency of thermophilic Campylobacter in broiler chickens during industrial
      processing in a Southern Brazil slaughterhouse.
AB  - 1. The frequency of thermophilic Campylobacter spp. on broiler carcases was
      determined during processing in a Southern Brazil slaughterhouse. Samples were
      collected after defeathering, evisceration, water chilling and freezing. In
      addition, samples were obtained from the water of the chiller tank and from the
      surface of equipment in direct contact with the chicken. 2. Samples (335) were
      analysed and 71.3% were positive for Campylobacter. The frequency of
      Campylobacter spp. on carcases rinsed in BPW and skin samples from carcases was
      49 of 72 (68.0%) after defeathering, 50 of 72 (69.4%) after evisceration, 61 of
      72 (84.7%) after chilling, and 46 of 72 (63.9%) after freezing. Campylobacter was
      positive for 21 of 23 (91.3%) samples in the chilling water and for 12 of 24
      (50.0%) samples on the table surface. 3. The frequency of qualitative analysis
      for Campylobacter spp. was reduced in frozen chickens, but not during the
      slaughtering process. The use of drinking water alone as a decontaminant to
      reduce the incidence of Campylobacter spp. during slaughter is therefore not
      sufficient. Furthermore, to ensure food safety, chickens must be cooked properly
      before consuming.

PMID- 17453804
TI  - Rapid quantification of avian eggshell microstructure and crystallographic
      texture using two-dimensional X-ray diffraction.
AB  - 1. It is important to quantify eggshell microstructure because it may influence
      eggshell mechanical properties and could be of importance for eggshell quality
      assessment. It also provides information about changes in eggshell associated
      with different hen physiological conditions. 2. This paper describes an
      alternative methodology which, based on 2D X-ray diffraction, allows eggshell
      microstructure quantification (for example, crystal size and orientation) much
      more efficiently than using traditional techniques (optical or scanning electron
      microscopy and conventional X-ray diffraction). 3. For such analyses, an X-ray
      diffractometer equipped with an area detector is used. Such equipment collects
      the diffraction pattern of the sample in one single exposure (taking a few tens
      of seconds), thus considerably reducing data acquisition time. 4. The two
      dimensional diffraction patterns obtained contain detailed information about size
      and crystallographic orientation of crystals forming the eggshell. This
      information can be automatically extracted using specially designed software. 5.
      Access to the software is available on a website, the address of which is given
      in the Materials and Methods section. 6. In this paper, specific examples of how
      these analyses are applied are set out and recommendations for obtaining
      different types of microstructure information are given. In addition, the
      limitations of the technique are discussed.

PMID- 17453805
TI  - Effects of electrical field on hatchability performance of eggs from a layer-type
      breeder.
AB  - 1. Eggs from a layer-type breeder flock (Baladi, King Saud University) between 50
      and 63 weeks of age were used in three trials to study the effects of electrical
      field (EF) during incubation on albumen and yolk heights, incubation temperature,
      egg weight loss and hatchability traits. The effects of egg size and eggshell
      characteristics on hatchability traits of eggs incubated under EF were
      investigated. 2. Eggs were weighed and graded into three weight classes (small,
      medium, and large). The physical dimensions, eggshell characteristics, and
      conductance of eggs were examined. The incubator was divided into two
      compartments for the control and EF treatments. Two aluminium plates were fitted
      on the inside walls of the EF compartment, face to face, and connected to a step
      up electric transformer. Eggs were exposed constantly to the EF during the first
      18 d of incubation at the level of 30 kV/m, 60 Hz. 3. Egg size influenced the
      physical dimensions and eggshell characteristics of eggs. Large eggs had higher
      egg weight, egg surface area, egg volume, eggshell conductance, and eggshell
      weight and lower yolk weight percentage than medium or small size eggs. Small
      eggs had lower egg length and higher egg density than large or medium size eggs.
      Large eggs had higher eggshell thickness than small size eggs. 4. EF incubation
      of eggs raised incubation temperature by 0.06 degrees C, and increased the
      percentage of egg weight loss, hatchability, and weight of hatching chicks and
      reduced the early embryo deaths, and length of incubation by approximately 9.8,
      19.6, 1.7, 62.1 and 2.1%, respectively. 5. There was no significant difference
      between the two incubation treatments in the heights of albumen and yolk of
      incubated eggs, percentages of late embryo deaths, and pips with live and dead
      embryos. Hatchability traits were not significantly influenced by egg size. 6. It
      was concluded that EF incubation of eggs increased hatchability, chick-hatching
      weight, and reduced the length of incubation of Baladi eggs. Differences in the
      physical dimensions and eggshell characteristics of eggs did not influence
      hatchability traits of eggs under EF incubation.

PMID- 17453806
TI  - Application of real-time ultrasound technology to estimate in vivo breast muscle
      weight of broiler chickens.
AB  - 1. Real-time ultrasound (RTU) is a fast, non-destructive and relatively
      inexpensive technique to estimate body composition in animals. 2. A total of 835
      Hubbard, Ross and Cobb broilers from different flocks were randomly selected,
      weighed and two RTU measurements were taken from both sides of their breast
      muscles (BM). Immediately following ultrasonography, broilers were processed and
      dissected to determine carcase, boneless BM, leg quarter and wing weights. Data
      were utilised to develop multiple linear regression equations (MLRE) to estimate
      carcase part weights. 3. Factors such as sex, age or genetic line did not
      contribute significantly to the accuracy of the models. The measurement in the
      right side was consistently more efficient than the left for estimating BM
      weight. 4. The following MLRE was estimated from live body weight (BW) and RTU
      area images: BM (g) = -94.3476 + 0.1518 * BW (g) + 5.1644 * BM-RTU area (cm2) (R2
      = 0.97). 5. Due to the allometric relationships among body parts the following
      equations were also estimated: Legs (g) = -56.6738 + 0.2846 * BW (g) + 2.1570 *
      BM-RTU area (cm2) (R2 = 0.98) and Total Meat Cuts (g) = -142.0567 + 0.4638 * BW
      (g) + 5.1236 * BM-RTU area (cm2) (R2 = 0.99). 6. The results indicated that it
      was possible to estimate BM and other carcase cut weights with high accuracy from
      RTU measurements.

PMID- 17453807
TI  - Characterisation of peacock (Pavo cristatus) mitochondrial 12S rRNA sequence and
      its use in differentiation from closely related poultry species.
AB  - 1. Poaching of peacocks, the national bird of India, is illegal. People kill this
      beautiful pheasant bird for tail feathers and mix the meat with chicken or
      turkey. Differentiation of the meat of these species is essential in order to
      address the ambiguity about the origin of the sample. 2. The present study was
      carried out to investigate the use of polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) of mitochondrial 12S rRNA gene for
      identification of these species. 3. Peacock mitochondrial 12S rRNA partial gene
      was amplified using universal primers, cloned and characterised. It was found to
      be 446 nucleotides long. 4. Sequence analysis revealed 86.8 and 84.1% similarity
      with reported turkey and chicken sequences, respectively. Sequence and
      phylogenetic analysis showed that the peacock is much closer to the turkey than
      the chicken. 5. PCR-RFLP of 446 bp amplicon using commonly available restriction
      enzymes AluI and Sau3AI produced a differential pattern for identifying these
      poultry species unambiguously.

PMID- 17453808
TI  - Regulation of taste-active components of meat by dietary leucine.
AB  - 1. Regulation of meat taste is one effective method for improvement of meat
      quality. In this study, effects of dietary leucine (Leu) content on taste-active
      components, especially free glutamate (Glu), in meat were investigated. 2.
      Broiler chickens (28 d old) were fed on diets with graded dietary Leu content
      (100, 130 or 150% of Leu requirement in NRC, 1994) for 10 d before marketing.
      Taste-active components of meat (free amino acids and ATP metabolites) and
      sensory score of meat soup were estimated. 3. Free Glu content, the main taste
      active component of meat, was significantly increased by dietary Leu. Compared
      with the Leu 130% group, free Glu was increased by 17% in the Leu 100% group.
      Free Glu of meat tended to decrease in the Leu 150% group. In contrast, inosine
      monophosphate content in meat did not change among all groups. 4. Sensory
      evaluation of meat soup from the Leu 100 and 150% groups showed that they had
      different meat tastes. Sensory scores of overall preference, umami taste and
      chicken-like taste were significantly higher in the Leu 100% group. 5. These
      results suggest that dietary Leu content is a regulating factor of free Glu in
      meat. Decreasing dietary Leu induces an increase in the free Glu content of meat
      and improves meat taste.

PMID- 17453809
TI  - Crop content in nutrient-restricted versus non-restricted organic laying hens
      with access to different forage vegetations.
AB  - 1. The purpose of this study was to evaluate how feed intake of organic layers
      varies according to type of forage vegetation available when hens are fed a
      normal concentrate for organic layers or a nutrient-restricted diet with whole
      wheat and oyster shells, assuming that the nutrient-restricted diet would reflect
      the capacity of the hens to forage. 2. Two 23-d experiments were arranged with
      chicken runs in a 2 x 2 factorial design with two types of complementary feed
      (concentrate with 184 g/kg dry matter (DM) crude protein vs whole wheat with 120
      g/kg DM crude protein) and two types of forage vegetation (grass/clover vs a
      mixture of forbs in experiment 1 and grass/clover vs chicory in experiment 2):
      each experiment was carried out in three replications. 3. Twice during each
      experiment two hens from each run were slaughtered - two in the evening and two
      the following morning. Subsequently, the birds' crops were removed. Crop content
      was separated into 8 fractions. 4. For most feed items crop content was found to
      be significantly higher in the evening than in the morning. 5. Complementary feed
      significantly influenced the content of several feed items in the crop. In both
      experiments wheat-fed hens had a significantly higher amount of soil in the crops
      and a significantly lower amount of weed seeds compared to the concentrate-fed
      hens. Plant material and grit stone were significantly more abundant in wheat-fed
      hens only in experiment 2 and numerically more abundant in experiment 1, whereas
      the amount of oyster shells was significantly higher in wheat-fed hens in
      experiment 1 and numerically higher in experiment 2. 6. Type of forage itself
      only significantly influenced the amount of soil in the crops in experiment 1 and
      amount of seeds in experiment 2, since more soil was found in hens foraging on
      the mixed forbs and more seeds were found in the hens foraging on the chicory
      plots, respectively.

PMID- 17453810
TI  - Effect of fructooligosaccharides and antibiotics on laying performance of
      chickens and cholesterol content of egg yolk.
AB  - 1. Nine hundred and sixty 25-week-old Lohmann Brown layers were randomly divided
      into 5 groups with 216 layers in each group. Layers in group one were fed a
      control diet, group 2 received the control diet plus 20 mg/kg zinc bacitracin and
      4 mg/kg colistinsulfate, and the remaining three groups received control diet
      plus 2000, or 4000, or 6000 mg/kg fructooligosaccharide (FOS). 2. The results
      showed improvements in egg production, feed consumption and feed conversion of
      layers when 2000 mg/kg FOS was added to the diets. 3. The results also showed
      some additional improvements in the group supplemented with 2000 mg/kg FOS,
      including increases in egg shell thickness, yolk colour and Haugh unit, and
      decreases in yolk cholesterol concentration. 4. However, larger (excessive) doses
      of FOS did not improve the performance of layers.

PMID- 17453811
TI  - Impact of feeding 2-hydroxy-4-(methylthio)butanoic acid and DL-methionine
      supplemented maize-soybean-rapeseed meal diets on growth performance and carcase
      quality of broilers.
AB  - 1. This experiment was conducted to compare the effectiveness of DL-2-hydroxy-4
      (methylthio)butanoic acid (HMTBA) and DL-methionine (DLM) on growth performance
      and carcase quality of broilers in a 2 x 3 x 2 factorial experimental design
      including two methionine (Met) sources, three equimolar levels of Met
      supplementation and two sexes. 2. No difference was observed between the two Met
      sources in growth performance and muscle deposition from 10 to 49 d. With
      increasing Met levels, average daily gain was increased in the starter, grower
      and overall phases, average daily feed intake was increased in the starter phase,
      and feed:gain ratio was decreased in the grower and overall phases. Met
      supplementation increased breast muscle content and decreased abdominal fat
      content. Broilers given HMTBA had breast and thigh muscle coloration that was
      characterised as superior to those fed DLM. 3. These results indicated that Met
      supplementation improved growth performance and carcase quality irrespective of
      the Met sources. Compared to DLM, HMTBA has the same molar bioefficacy for
      improving the growth performance and carcase quality; however, HMTBA-fed birds
      had superior meat colour to DLM-fed birds.

PMID- 17453812
TI  - Effects of feeding raw or reconstituted high tannin red sorghum on nutrient
      utilisation and certain welfare parameters of broiler chickens.
AB  - 1. A feeding trial was conducted on 360 1-d-old chicks from 0 to 6 weeks of age
      to assess the effect of processed high tannin red sorghum in the diet of broiler
      chickens on nutrient utilisation and certain welfare parameters. 2. Each of 9
      dietary treatments was allotted to 4 groups (replicates) of chicks in a
      completely randomised design. The treatments were a maize-soy based standard
      broiler diet (control, RS(0)) and eight test diets formulated by incorporating
      either raw red sorghum (RS(25), RS(50), RS(75), RS(100)) or reconstituted red
      sorghum (RS(25)(R), RS(50)(R), RS(75)(R), RS(100)(R)) replacing 25, 50, 75 or
      100% of maize from the control diet. 3. The tannin content was reduced from 23 to
      16 g/kg in reconstituted red sorghum. 4. Utilisations of nitrogen, calcium and
      phosphorus retention were similar in all the dietary groups. 5. The cell-mediated
      immune response measured as footpad index (FPI) value of birds given raw red
      sorghum was significantly higher than in control and reconstituted red sorghum
      groups. Similarly, comparatively better humoral response measured as HA titre
      value was observed in raw red sorghum based groups than in reconstituted ones. 6.
      Plasma albumin, globulin, protein, glucose, calcium, phosphorus, SGOT, SGPT and
      uric acid levels did not differ significantly due to dietary treatments. 7. Mild
      histopathological changes were observed in liver and kidney tissues of birds
      given raw red sorghum. 8. From the present study, it is concluded that (1) the
      reconstitution of high tannin red sorghum resulted in about 30% reduction in its
      tannin concentration; (2) the feeding of reconstituted sorghum based diets to
      broiler chickens did not exert any appreciable influence on nutrient utilisation,
      blood biochemicals and enzymes and gross pathological changes; and (3) the birds
      fed on raw red sorghum exhibited higher immuno-responsiveness in comparison to
      their reconstituted counterparts.

PMID- 17453813
TI  - Nitrogen requirement for maintenance in Yangzhou goslings.
AB  - 1. Experiments were conducted to determine the nitrogen (N) requirement for
      maintenance (N(m)) in Yangzhou goslings. 2. At 56 d old, 18 birds were divided
      into three equal groups and fed on diets with equal metabolisable energy (ME) and
      different contents of crude protein (CP; low, medium and high) in an N balance
      test. N(m) was estimated from the relationship between N output (N(E)) and N
      intake (N(I)). Following the above N balance test, 16 goslings at the same age
      were used in a N balance test with an N-free diet. The birds were divided into 4
      equal groups and offered an N-free diet at intakes of 90, 70, 50 and 0 g per d,
      respectively. 3. The estimated N(m) was 240 mg/kg BW(0.75) per d in the N balance
      test. The result from the N-free diet trial gave a value of 244 mg/kg BW(0.75)
      per d, confirming the result of the N balance test. The lower intake of N-free
      diet resulted in more N(E), suggesting that protein catabolism may occur in the
      body of birds to meet N(m) when dietary N(I) was very low. 4. It was concluded
      that the N(m) of Yangzhou goslings was about 240 mg/kg BW(0.75).

PMID- 17453814
TI  - Effect of cellulase supplementation in low-crude protein diets on performance,
      nitrogen excretion, fat deposition, hepatic lipogenic and lipolytic enzyme
      activity in broilers.
AB  - 1. Two experiments were conducted to investigate the effect of dietary enzyme
      supplementation of a low-protein diet on performance, nitrogen excretion, fat
      deposition, hepatic lipogenic and lipolytic enzyme activity in 7-21- (Experiment
      1) and 21-42-d-old (Experiment 2) male broiler chicks. 2. Chicks were given diets
      containing 210 g (Experiment 1) or 170 g (Experiment 2) crude protein (CP)/kg
      (Control), amino acid-fortified diets 190 g (Experiment 1) and 150 g (Experiment
      2) CP/kg (Low-protein), and a low-protein diet supplemented with 1000 U/kg of
      cellulase. 3. In Experiment 1, growth performance and abdominal fat deposition
      were not affected by dietary treatments, and birds given low-protein diets
      excreted less nitrogen. The activities of hepatic lipogenic and lipolytic enzymes
      were not different among the three dietary groups. 4. In Experiment 2, the
      dietary treatment did not affect growth performance or abdominal fat weight.
      Nitrogen excretion was significantly lower in chicks given the 150 g/kg CP diet
      than those on the 170 g/kg CP diet; however, nitrogen retention was no different
      among the treatments. Dietary CP and enzyme supplementation did not significantly
      affect hepatic enzyme activities. 5. These results suggest that CP content in the
      broiler diet can be reduced by 20 g/kg without lowering performance by the
      supplementation of crystalline amino acids, and can reduce nitrogen excretion by
      about 25%. Cellulase supplementation of a low-CP diet slightly lowered abdominal
      fat deposition; however, it did not significantly affect hepatic lipogenic and
      lipolytic enzyme activity.

PMID- 17453815
TI  - Effect of conjugated linoleic acid on growth performances, carcase composition,
      plasma lipoprotein lipase activity and meat traits of chickens.
AB  - 1. The effects of dietary conjugated linoleic acid isomers (CLAs) on productive
      traits, carcase yield and meat quality were investigated in Beijingyou (Chinese)
      chickens. A total of 360 male chicks were allocated to 5 dietary treatments
      (0.00, 0.25, 0.50, 1.00 and 2.00% CLA) and fed for 126 d. 2. The results showed
      that CLA supplementation did not significantly influence body weight, but
      increased feed conversion and decreased intramuscular fat in breast and thigh
      muscles. Mortality was significantly higher in the control group. 3. The addition
      of 1.0 and 2.0% CLA decreased abdominal fat percentages. At CLA dietary levels
      greater than 0.5%, lipoprotein lipase activity in plasma was significantly
      decreased. 4. Hunter L* and a* values were not significantly affected by CLA
      supplementation. However, Hunter b* values were lower in chickens supplemented at
      levels greater than 0.5% CLA. Supplementing diets with CLA modified the fatty
      acid composition of breast muscle. The proportions of CLA, saturated and
      polyunsaturated fatty acids were increased whereas the proportion of
      monounsaturated fatty acids was decreased.

PMID- 17453816
TI  - A mechanistic, stochastic, population model of egg production.
AB  - 1. A mechanistic, stochastic egg production model is presented. Mean age at first
      egg may be predicted from the lighting programme applied during rearing, using
      the Bristol-Reading model (Lewis et al., 2002). 2. Rate of ovulation is
      determined by an amended version of the mathematical model of the ovulatory
      cycle, originally proposed by Etches and Schoch (1984). 3. Oviposition times are
      estimated from ovulation times. 4. Yolk, albumen and shell weights are calculated
      using allometric functions. 5. The model predicts egg production of a theoretical
      flock of laying hens for a full laying year, including random occurrences of
      double-yolked and soft-shelled eggs and internal ovulations.

PMID- 17453817
TI  - Expression and localisation of calbindin D28k in all intestinal segments of the
      laying hen.
AB  - 1. The aim of the present study was to investigate expression and localisation of
      a 28-kDa calcium-binding protein (CaBP-D28k) related to active calcium (Ca)
      absorption, in the entire intestine of egg-laying hens. 2. Western blotting
      analysis showed that the entire intestine expressed CaBP-D28k to the following
      degree: duodenum > jejunum > caecum > ileum > colon. Immunohistochemistry showed
      strong CaBP-D28k localisation in enterocytes along the villus tip-crypt axis in
      the duodenum and in villus tips in the caecum and colon. The jejunum and ileum
      had moderate localisation with respect to the number of immunoreactive cells and
      staining intensity. 3. These results suggest that laying hens actively absorb Ca
      in both the large and small intestines.

PMID- 17453818
TI  - Downregulation of missing in metastasis gene (MIM) is associated with the
      progression of bladder transitional carcinomas.
AB  - Missing in metastasis (MIM) gene encodes a putative metastasis suppressor.
      However, the role of MIM in tumorigenesis and metastasis has not yet been
      established. Western blot analysis using a MIM specific antibody demonstrated
      that MIM protein is present at varying levels in a variety of normal cells as
      well as tumor cell lines. Immunohistochemical staining of adult mouse tissues
      revealed abundant MIM immunoreactivity in uroepithelial cells in the bladder,
      neuron Purkinje cells in the cerebellum, and megakaryocytes in the bone marrow
      and spleen in addition. MIM immunoreactivity also was found in human normal
      bladder transitional epithelial cells. However, the reactivity was not seen in 69
      percent of human primary transitional cell carcinoma specimens. Over 51 percent
      of the tumors at low grade display MIM staining similarly to the normal cells,
      whereas only 16.7 percent of the tumors at high-grade with poor differentiation
      show faint or mild staining. Furthermore, full-length MIM protein is highly
      expressed in SV-HUC-L an immortalized normal transitional epithelial cell line,
      moderately expressed in T24 and poorly expressed in J82 and TCCSUP transitional
      cell carcinoma cells. This finding indicates that downegulation of MIM expression
      may correlate with the transition of tumor cells from distinct epithelium-like
      morphology to less differentiated carcinomas.

PMID- 17453819
TI  - A 5-drug regimen maximizing the dose of cyclophosphamide is effective therapy for
      adult Burkitt or Burkitt-like lymphomas.
AB  - Burkitt lymphoma (BL) and Burkitt-like lymphomas (BLL) are clinically and
      biologically aggressive B-cell malignancies. Brief-duration, high intensity
      multidrug regimens with central nervous system (CNS) prophylaxis have proven to
      be effective, with published series of adult patients documenting complete
      response (CR) rates of 80 to 100 percent and 2-year event-free survival (EFS)
      rates ranging from 60 to 90 percent. Based upon the known sensitivity of BL to
      cyclophosphamide and favorable results reported from the Dana Farber Cancer
      Center using high-dose CHOP in diffuse aggressive lymphomas, we tested a regimen
      designed to maximize the administered dose of cyclophosphamide while eliminating
      other agents commonly used in BL protocols. Eleven patients with Burkitt or
      Burkitt-like lymphoma were treated with 4 cycles of a 5-drug regimen, called high
      dose CHOP, which contains a cyclophosphamide dose of 4 gm/m2 with each cycle.
      Intrathecal methotrexate and midcycle high-dose methotrexate were added as CNS
      prophylaxis. Ten patients achieved a complete response (91 percent) and with a
      median follow up of 38 months, the 3-year EFS is 64 percent and the 3-year
      overall survival (OS) is 72 percent. Three patients recurred after the
      achievement of a CR. Treatment-related toxicities included myelosuppression,
      neutropenic fevers/infections, and tumor lysis syndrome requiring hemodialysis in
      2 patients. There were no treatment-related deaths and none of the patients had
      to discontinue therapy secondary to toxicity. In conclusion, the high-dose CHOP
      with midcycle methotrexate regimen produces response rates and EFS rates
      comparable to other regimens, with an acceptable toxicity profile. Utilization of
      high dose cyclophosphamide may eliminate the need for several other agents in
      Burkitt lymphoma regimens.

PMID- 17453820
TI  - Tumor suppressor proteins are differentially affected in human ependymoblastoma
      and medulloblastoma cells exposed to nerve growth factor.
AB  - The aim of our study was to investigate the role of nerve growth factor (NGF) on
      the expression of the p73 protein in human ependymoblastoma (EP) and
      medulloblastoma (MB) cells. It was found that NGF exposure on MB cells blocks
      proliferation, as well as on EP cells and induces overexpression of p73. NGF
      reduces the number of cells and promotes the expression of TrkA of these
      neoplastic cells. Moreover, NGF plus cisplatin treatment reduces the cytotoxic
      effect of cisplatin. These observations indicate that NGF by interfering with
      mechanisms associated with cells proliferation and survival might induce the
      differentiation event through TrkA pathways.

PMID- 17453822
TI  - Functioning and activity participation restrictions among older adult, long-term
      cancer survivors.
AB  - This research examines how cancer and treatment sequelae combine with
      comorbidities to influence the physical functioning and activity participation
      restrictions reported by older adult (> or =60), long-term survivors (5+ years)
      of breast, prostate, and colorectal cancer. The number of current comorbidities
      was the best predictor of functional difficulties and also a significant
      predictor of participation restrictions. Cancer stage at diagnosis and continuing
      cancer symptoms had direct effects on functional difficulties, and indirect
      effects through functional difficulties on participation restrictions. Clinicians
      working with older adult survivors need to be aware of the interplay between
      cancer and other health problems as they affect quality of life after cancer.

PMID- 17453821
TI  - Clinical evaluation of the use of exemestane as further hormonal therapy after
      nonsteroidal aromatase inhibitors in postmenopausal metastatic breast cancer
      patients.
AB  - OBJECTIVES: The aromatase inhibitors Anastrozole, Letrozole (type 2 nonsteroidal
      aromatase inhibitors: n-SAI) and Exemestane (type 1 steroidal aromatase
      inactivator) are used respectively as first- and second-line hormonal therapy in
      postmenopausal metastatic breast cancer women. Few clinical data are published on
      the sequential use of different classes of aromatase inhibitors. METHODS: We
      report an analysis on 30 postmenopausal metastatic breast cancer women treated
      between January 2000 and May 2002 in 2 Italian Oncology Institutions with the
      hormonal sequence n-SAI (Anastrozole, Letrozole) --> Exemestane. RESULTS: When
      receiving n-SAI (Anastrozole 8 patients and Letrozole 22 patients), 1 out of 30
      women achieved a partial response, 20 of 30 patients no change (NC) > or =6
      months. The analysis of the entire population treated with Exemestane showed an
      overall clinical benefit (CB) of 46.6 percent (14/30) with a median duration of
      12 months (95%CI 6-25) and a median time to progression (TTP) of 4 months (95%CI
      1-25). CONCLUSIONS: These data confirm a partial lack of cross-resistance between
      n-SAI --> Exemestane given in sequence.

PMID- 17453823
TI  - 6-mercaptopurine (6-MP) entrapped stealth liposomes for improvement of leukemic
      treatment without hepatotoxicity and nephrotoxicity.
AB  - 6-mercaptopurine (6-MP) is a purine analogue used in childhood leukemia. Because
      of the oral bioavailability of 6-MP is low and highly variable, the aim of this
      study was to develop a new parenteral formulation that can prolong the biological
      half-life of the drug, improve its therapeutic efficacy, and its associated
      reduce side effects. Conventional and stealth 6-MP liposomes were prepared by a
      thin film hydration technique followed by a high-pressure homogenization process
      and characterized for percent entrapment efficiency (%EE), particle size, and
      stability in human plasma. Pharmacokinetic, tissue distribution, and biochemical
      analysis were performed after intravenous (IV) administration of all formulations
      of 6-MP on rats. The conventional liposomes were found less stable than stealth
      liposomes in human plasma at 37 degrees C. Stealth liposomes exhibited high peak
      plasma concentration (C(max)), and long circulating capacity in blood and
      biological half-life. The uptake of stealth liposomes by the liver and spleen and
      accumulation in the kidney were significantly less than that of conventional
      liposomes and the free drug. Serum urea, creatinine, GOT (Glutamic Oxaloacetic
      Transaminase), and GPT (Glutamic Pyruvic Transaminase) increased significantly in
      rats given an IV injection of conventional liposomes and the free drug, but not
      in those administered with the same dose of stealth liposomes. Stealth liposomes
      may help to increase therapeutic efficacy of 6-MP and to reduce total amount of
      dose as well as frequency of the dose. It also may reduce the possibility of the
      risk of toxicity to the liver and kidney generally associated with free 6-MP.

PMID- 17453824
TI  - Ethical and design issues of phase I clinical trials in cancer patients.
AB  - Therapeutic clinical trials are an absolute necessity to enhance the therapy of
      serious illnesses, and Phase I trials are the only way to introduce new
      therapeutic modalities into use in human beings. However, since the first
      obligation a physician has is to the individual patient's well-being and
      avoidance of doing harm, offering such patients an unproven therapy with low
      probability of benefit to him/herself and significant potential toxicities poses
      major ethical problems. These ethical problems can only be solved by full
      disclosure of all facts to the patient, a detailed explanation that the primary
      goal of the trial is to improve medical care (altruistic motivation), and by
      making sure that in addition to the trial mandated treatment the patient receives
      optimal palliative care, including hospice care when needed.

PMID- 17453825
TI  - The evolving role of CT colonography.
AB  - Colorectal cancer (CRC) screening is widely recommended as part of standard
      preventive care. All average risk persons over the age of 50 y are eligible.
      Various authorities have advocated fecal occult blood testing, flexible
      sigmoidoscopy, barium enema and colonoscopy at varying intervals as acceptable
      screening options. Despite the array of choices, CRC screening lags in frequency
      behind other cancer screening maneuvers like mammography or Pap smear. Of late,
      there is growing interest in CT colonography (CTC) as another screening option.
      CTC, or virtual colonoscopy, may represent an attractive, non-invasive method of
      CRC screening that provides images akin to traditional colonoscopy. Improvements
      in CTC performance, especially when coupled with declining costs, suggest that
      CTC's role in average risk screening will increase in the future. This review
      summarizes available data about the efficacy of CTC in average and high risk
      screening populations. Current indications as well as limitations to this
      technology are discussed, as are practical issues like the cost-effectiveness of
      CTC for widespread use.

PMID- 17453826
TI  - Beta-endorphin regulation of MAPKs in cultured human articular chondrocytes: MAPK
      inhibitors prevent the increase of IL-1 beta protein levels during beta-endorphin
      stimulation.
AB  - We investigated the effect of beta-endorphin on the activities of mitogen
      activated protein kinases in cultured human articular chondrocytes in order to
      elucidate its effect on cartilage. Monolayer cultures of chondrocytes obtained
      from patients undergoing total knee arthroplasty were treated with 60, 600, or
      6000 ng/ml beta-endorphin, or 100 ng/ml naltrexone combined with 600 ng/ml beta
      endorphin. The regulation of three major mitogen-activated protein kinases
      phosphorylation, ERKp44/p42, p38, and JNK, was determined by Western blotting. We
      also examined the influence of specific mitogen-activated protein kinase
      inhibitors on IL-1 beta protein levels during beta-endorphin stimulation. The
      results demonstrate that beta-endorphin, dependent on concentration and duration
      of stimulation, significantly affected the activation of the three mitogen
      activated protein kinases in cultured human articular chondrocytes. Naltrexone in
      some cases significantly regulated the mitogen-activated protein kinases in
      different ways when added to beta-endorphin 600 ng/ml. Furthermore, specific
      mitogen-activated protein kinase inhibitors hindered the increase of IL-1 beta
      during beta-endorphin incubation. The effect of beta-endorphin seen in this study
      is considered critical for the production of several mediators of cartilage
      damage in an arthritic joint.

PMID- 17453827
TI  - Cell adhesion dynamics and actin cytoskeleton reorganization in HepG2 cell
      aggregates.
AB  - The temporal dependence of cytoskeletal remodelling on cell-cell contact in HepG2
      cells has been established here. Cell-cell contact occurred in an ultrasound
      standing wave trap designed to form and levitate a 2-D cell aggregate, allowing
      intercellular adhesive interactions to proceed, free from the influences of solid
      substrata. Membrane spreading at the point of contact and change in cell
      circularity reached 50% of their final values within 2.2 min of contact.
      Junctional F-actin increased at the interface but lagged behind membrane
      spreading, reaching 50% of its final value in 4.4 min. Aggregates had good
      mechanical stability after 15 min in the trap. The implication of this temporal
      dependence on the sequential progress of adhesion processes is discussed. These
      results provide insight into how biomimetic cell aggregates with some liver cell
      functions might be assembled in a systematic, controlled manner in a 3-D
      ultrasound trap.

PMID- 17453828
TI  - Melanoma-associated antigen family protein-D1 regulation of tumor cell migration,
      adhesion to endothelium, and actin structures reorganization in response to
      hypoxic stress.
AB  - Melanoma-associated antigen family protein-D1 (MAGE-D1) is a recently identified
      p75 neurotrophin receptor intracellular binding protein and functions as an
      adaptor that mediates multiple signaling pathways, including Dlx/Msx-mediated
      transcription. Here, a new regulatory function for MAGE-D1 in tumor cell motility
      and adhesion to endothelium is described. MAGE-D1 over-expression suppressed HeLa
      cell and BEL7402 cell migration, invasion, and adhesion to the monolayer of
      ECV304 cells. We also report that MAGE-D1 over-expression disrupted actin
      cytoskeleton rearrangement induced by hypoxia and down-regulated hypoxia
      inducible factor 1-dependent luciferase gene expression. These findings provide
      new insight into the ability of MAGE-D1 to suppress the motility and adhesion
      response of tumor cells by interfering with actin cytoskeleton reorganization and
      hypoxia inducible factor 1-dependent gene expression.

PMID- 17453829
TI  - F-actin binding region of SPIN90 C-terminus is essential for actin polymerization
      and lamellipodia formation.
AB  - We recently reported that SPIN90 is able to bind with several proteins involved
      in regulating actin cytoskeleton networks, including dynamin, WASP, beta PIX, and
      Nck. Based on these findings, we investigated how SPIN90 regulates the actin
      cytoskeleton and promotes actin assembly. This study demonstrated that aluminium
      fluoride-induced localization of SPIN90 to lamellipodia requires amino acids 582
      722 at the SPIN90 C-terminus, which is also essential for F-actin binding and
      Arp2/3 complex mediated polymerization of actin into branched actin filaments.
      Furthermore, after deletion of the F-actin binding region (582-722 SPIN90) failed
      to localize at the membrane edge and was unable to promote lamellipodia
      formation, suggesting that the F-actin binding region in the SPIN90 C-terminus is
      essential for the formation of branched actin networks and regulation of the
      actin cytoskeleton at the leading edge of cells.

PMID- 17453830
TI  - Visuospatial working memory in school-aged children exposed in utero to cocaine.
AB  - OBJECTIVE: Among the neurocognitive impairments reported as associated with
      prenatal cocaine exposure, slower response time, and less efficient learning in
      school-aged children are common to findings from several laboratories. This study
      presents performance data on a spatial working memory task in 75 prenatally
      cocaine exposed (CE) and 55 nondrug-exposed (NDE) 8- to 10-year-old children.
      METHODS: Children were administered a novel neuropsychological measure of
      immediate- and short-term memory for visuospatial information, the Groton Maze
      Learning Test (GMLT), a computer-based hidden maze learning test that consists of
      a "timed chase test" (a simple measure of visuomotor speed), eight learning
      trials followed by a delayed recall trial after an 8-minute delay and a reverse
      learning trial. Performance is expressed as correct moves per second and number
      of errors per trial. RESULTS: Across all trials, the cocaine-exposed group showed
      significantly slower correct moves per second and made significantly more errors.
      There were no significant main effects for amounts of alcohol, tobacco, or
      marijuana exposure. After an 8-minute delay and compared to the eighth trial,
      cocaine-exposed children showed less consolidation in learning compared to
      nonexposed children. When asked to complete the maze in reverse, cocaine-exposed
      children showed a greater decrement in performance (decreased correct moves per
      second and increased errors) compared to the eighth learning trial. CONCLUSIONS:
      Children exposed in utero to cocaine exhibit a possible impairment in procedural
      learning and diminished efficiency in creating and accessing an internal spatial
      map to master the hidden maze.

PMID- 17453831
TI  - Prospective memory and pediatric traumatic brain injury: effects of cognitive
      demand.
AB  - This study investigated the effects of pediatric traumatic brain injury (TBI) on
      prospective memory. Fourteen children and 14 adolescents with TBI were compared
      with 25 and 23 noninjured children and adolescents, respectively. Based on a
      prefrontal model, the cognitive demand on the ongoing component of a prospective
      memory task was manipulated. Overall, those with TBI had poorer prospective
      memory performance than their noninjured peers. Performance was worse in a high
      cognitive-demand condition than a low, and younger children performed worse than
      adolescents. Decreases in performance from the low- to high-demand conditions
      were not significantly different between the two children's groups but were
      between the two adolescents' groups. Furthermore, the age and injury effects were
      reflected in the performances on executive function tests: the Self-ordered
      Pointing Task (SOPT), and the Stroop Color Word Interference Test. The Tower of
      London (TOL), which did not produce age or injury effects, was nevertheless found
      to be an important predictor of performance on the high-demand task in those with
      TBI. Although previous research has demonstrated impaired prospective memory
      performance in children with TBI, this study attempted to explain why this might
      occur, specifically that the prefrontal regions might be implicated.

PMID- 17453832
TI  - Recovery in memory function, and its relationship to academic success, at 24
      months following pediatric TBI.
AB  - While a number of research papers have reported findings on memory deficits
      following traumatic brain injury (TBI), only limited studies have monitored the
      recovery of these skills over time. The present study examined memory ability and
      its effect on academic success in a group of children who had sustained a mild,
      moderate, or severe traumatic brain injury (TBI). Results showed that the severe
      TBI group exhibited greater deficits on memory tasks, irrespective of modality,
      in the acute, 6-, 12-, and 24-month postinjury stages, in comparison to mild and
      moderate TBI groups. Performance on academic measures was dependent on both
      injury severity and task demands. Preinjury academic ability and verbal memory
      indices best predicted academic success.

PMID- 17453833
TI  - Speech perception and motor control in children with Down syndrome.
AB  - Twelve children with and without Down syndrome (DS) performed eight subtests of
      an apraxia battery to determine under what conditions children with DS had
      difficulty performing representational and nonrepresentational gestures.
      Participants with DS also completed a dichotic listening test. Participants with
      DS performed just as well as control participants on all aspects of the apraxia
      battery except a subtest in which they were required to pantomime tool use from
      verbal instruction. This suggests that children with DS have difficulty
      generating an action from memory following verbal instruction. Given the
      sufficient context or visual demonstration, children with DS performed similar to
      the other participants. As well, there was a great deal of within-group
      variability for dichotic listening ear advantage. Participants with a greater
      left ear advantage on the dichotic listening test committed more errors on an
      imitation test that also included a verbal component than participants with a
      greater right ear advantage.

PMID- 17453834
TI  - Performance of children with attention deficit hyperactivity disorder (ADHD) on a
      test battery of impulsiveness.
AB  - Children with ADHD were compared to healthy controls on a task battery of
      cognitive control, measuring motor inhibition (Go/No-Go and Stop tasks),
      cognitive inhibition (motor Stroop and Switch tasks), sustained attention and
      time discrimination. Children with ADHD showed an inconsistent and premature
      response style across all 6 tasks. In addition they showed task-specific
      impairments in measures of sustained attention, time discrimination, and motor
      inhibition, but spared cognitive inhibition. Measures of impairment correlated
      with behavioral hyperactivity and with each other, suggesting that they measure
      interrelated aspects of a multifaceted construct of cognitive impulsiveness. The
      task battery as a whole showed 76% correct discrimination of cases and controls.

PMID- 17453836
TI  - Sin and disease in a post-christian culture: an introduction.

PMID- 17453837
TI  - The original risk: overtheologizing ethics and undertheologizing sin.
AB  - The project of articulating a theological ethics on the basis of liturgical
      anthropology is bound to fail if the necessary consequence is that one has to
      quit the forum of critical modern rationality. The risk of Engelhardt's approach
      is to limit rationality to a narrow vision of reason. Sin is not to be understood
      as the negation of human holiness, but as the negation of divine holiness. The
      only way to renew theological ethics is to understand sin as the anthropological
      and ethical expression of the biblical message of the justification by faith
      only. Sin is therefore a secondary category, which can only by interpreted in
      light of the positive manifestation of liberation, justification, and grace. The
      central issue of Christian ethics is not ritual purity or morality, but
      experience, confession and recognition of our own injustice in our dealing with
      God and men. 

PMID- 17453838
TI  - Why ecumenism fails: taking theological differences seriously.
AB  - Contemporary Christians are separated by foundationally disparate understandings
      of Christianity itself. Christians do not share one theology, much less a common
      understanding of the significance of sin, suffering, disease, and death. These
      foundational disagreements not only stand as impediments to an intellectually
      defensible ecumenism, but they also form the underpinnings of major disputes in
      the culture wars, particularly as these are expressed in healthcare. There is not
      one Christian bioethics of sin, suffering, sickness, and death. In this article,
      the character of the moral-theological visions separating the various
      Christianities and thus their bioethics is examined. Particular emphasis is
      placed on the differences that set contemporary Western theology at odds with the
      theology of the Christianity of the first millennium. As is shown, the ground for
      this gulf lies in the divide between traditional and post-traditional views of
      the appropriate role of philosophy in theology, a difference rooted in disparate
      understandings of the meaning of church and of the meaning of the logos, the Son
      of God. 

PMID- 17453839
TI  - How philosophy and theology have undermined bioethics.
AB  - This essay begins by distinguishing among the viewpoints of philosophy, theology,
      and religion; it then explores how each deals with "sin" in the bioethical
      context. The conclusions are that the philosophical and theological viewpoints
      are intellectually defective in that they cripple our ability to deal with
      normative issues, and are in the end unable to integrate Christian concepts like
      "sin" successfully into bioethics. Sin is predicated only of beings with free
      will, though only in Western Christianity must all sins be committed with
      knowledge and voluntarily. Without the notions of free will, sin, and a narrative
      of redemption, bioethics remains unable to provide itself with an adequate
      normative framework. Bioethics, and morality in general, remain a morass
      precisely because there has been a failure to translate Christian morality into
      fully secular and scientistic terms. 

PMID- 17453840
TI  - Illness, disease and sin: the connection between genetics and spirituality.
AB  - The New Testament, while rejecting any superficial connection between illness and
      sin, does not reject a possible connection between illness and a person's
      relationship with God. An example can be seen in the story of the young blind man
      who was healed (St. John 9:3). His blindness does not result from any fault he or
      his parents had committed but apparently from God's wish to reveal his own
      healing power. The inner blindness of the Pharisees is a different type of
      blindness far more difficult to heal. The blind young man was actually healed,
      not only in body but also in soul. Such miraculous healings are rare nowadays.
      However, if one takes a closer look at modern genetics and psycho-neuro
      immunological findings, one may come to a better understanding of how miracle
      healings are linked to man's inner life and therefore also to his religiousness.
      Many diseases have genetic backgrounds. Defective genes, however, do not
      necessarily lead to subsequent illness. Genes have to be switched on or off. Only
      activated genes trigger pathological change. The human brain and all of man's
      thinking and feeling are intimately connected with such activations. We may thus
      conclude that both inner life and religious outlook on life are relevant to the
      origin and development of diseases. 

PMID- 17453841
TI  - Illness, Disease, and Sin: the Connection between Genetics and Spirituality - A
      Response.
AB  - In responding to Mathias Beck's thought-provoking article, it seems helpful to
      begin with an outline and comments on Beck's case as I understand it. For me,
      this overview throws up three problematic areas that I explore further under the
      headings of 1. examining the New Testament evidence, 2. sin as disobedience, and
      3. obedience, grace, and freedom. Clearly, the author's thoughts in all their
      nuances are not always adequately accessible in translation. Nevertheless, I hope
      that I have grasped the main thread of his argument. If I am right in my
      interpretation then Beck still has work to do to clarify and make explicit what
      is not only barely implicit but what is obscured by his central theme: that
      obedience to God's will is the mainstay of our relationship to God. 

PMID- 17453842
TI  - Resisting the therapeutic reduction: on the significance of sin.
AB  - Sin-talk, though politically incorrect, is indispensable. Placing human life
      under the "hermeneutic of sin" means acknowledging that one ought to aim
      flawlessly at God, and that one can fail in this endeavor. None of this can be
      appreciated within the contemporary post-Christian, mindset, which has attempted
      to reduce religion to morality and culture. In such a secular context, the guilt
      feelings connected with the recognition of sin are considered to be harmful; the
      eternal benefit of a repentance is disregarded. Nevertheless, spirituality
      appears to have therapeutic benefits. Therefore attempts are made to re-locate
      within healthcare a religion shorn of its transcendent claims, so as then to
      harvest the benefits of a spirituality "saved from sin". This reduction of
      religiosity to its therapeutic function is nourished by a post-modern
      constructivist construal of religion. This article critically examines the dis
      ingenuity marring such recasting, as well as the incoherence of related attempts
      to reduce transcendence to solidarity, and to re-shape the significance of
      religious rituals. 

PMID- 17453843
TI  - Molecular circadian rhythms in central and peripheral clocks in mammals.
AB  - The last decade has seen tremendous progress in our understanding of the
      organization and function of the circadian clock. A number of so-called clock
      genes were discovered, and these genes and their protein products were shown to
      organize into feedback loops to give a near 24 h rhythmicity. However, the
      mechanism is much more complicated. First, many new clock components have been
      identified, increasing both our understanding and the overall complexity of the
      mechanism. Second, there is now evidence that transcription may not play a
      central role in determining the functioning of the clock: the identification of
      post-translational modifications of the clock proteins has revealed new levels of
      control. Finally, chromatin remodeling seems to be crucial in the regulation of
      the expression of major clock components. This review describes the recent
      advances in our knowledge of the molecular clockwork in mammals; in particular,
      the contribution of new clock components and of post-transcriptional and post
      translational events to circadian timekeeping are discussed.

PMID- 17453844
TI  - Effects of transient and continuous wheel running activity on the upper and lower
      limits of entrainment to light-dark cycles in female hamsters.
AB  - The entrainment limits to light-dark cycles can be modified by the experimental
      conditions under which they are tested. Among the factors that may influence
      entrainment is the amount of wheel running exerted by the animal. In the present
      work, the effects of transitory and continuous wheel running on entrainment to
      light-dark cycles were tested using a range of T cycles at the entrainment
      limits. Four groups of female hamsters were submitted to 1 h stepwise changes in
      T cycles. Two groups were exposed to T cycles of which the period was shortened
      at the lower limit from T22 to T18, and the other two groups were exposed to
      cycles that lengthened at the upper limit from T27 to T32. One of the groups at
      the lower limit and one at the upper limit had continuous access to a running
      wheel, while the others had the wheel locked, except at certain T when a lack of
      period control by T cycle appeared. The study demonstrates that access to running
      wheel widens the limits of entrainment to LD cycles. Specifically, the following
      observations were made: the effects of wheel running for entrainment were more
      evident in the groups with continuous access to wheel, as they did entrain to T19
      and T32; continuous access to a wheel produced aftereffects only after T19, but
      not under T32; and when animals without a wheel showed relative coordination,
      unlocking the wheel favored entrainment in all the animals at T31, but in only 1
      out 6 at T19. All of these indicate a different effect of the wheel running on
      the upper and lower limits of entrainment.

PMID- 17453845
TI  - Daily laying time in free-living European starlings: solar noon, a potential
      synchronizer.
AB  - Reproduction is generally controlled by important temporal constraints involving
      complex adaptive mechanisms. Birds, in temperate zones, present marked breeding
      seasonality as well as marked daily organization of reproductive behavior,
      especially laying. Intra-specific variability and determinants of this pattern
      have been investigated mainly in domestic non-passerine birds. The present study
      analyzed the daily temporal organization of laying in a free-living species, the
      European starling, Sturnus vulgaris. Breeding in a starling colony was monitored
      for five consecutive years using a non-invasive method (infrared video camera) to
      precisely estimate laying times. European starlings present a marked daily laying
      rhythm, ovipositions occurring only during a morning species-specific temporal
      window. Inside this laying window, time intervals between successive eggs varied
      greatly among females. Contrary to many species, the light/dark cycle did not
      appear to control laying time in European starlings, but daily variations of the
      ultraviolet composition of the solar spectrum appeared to be a possible Zeitgeber
      of this behavior.

PMID- 17453846
TI  - Stable individual profiles of daily timing of migratory restlessness in European
      quail.
AB  - Temporal characteristics of migratory behavior in birds are usually studied at
      the species and population levels, and rarely at the individual level. Variations
      among species and populations of the seasonal onset of migratory behavior have
      been widely investigated, but very little is known about its daily organization
      or whether birds are conservative in their behavior. The determination of intra-
      and inter-individual variability is important for the study of genetic variations
      and can reveal the existence of different adaptation capacities within
      populations. This laboratory study analyzed intra- and inter-individual
      variability of daily initiation and time course of nocturnal restlessness in
      partial-migrant European quail (Coturnix coturnix coturnix). Thirty-five quail
      were selected randomly from a captive stock, and their spring activity was
      recorded under natural daylenghs. Eighteen of the thirty-five quail presented
      behavioral profiles of migrant birds. Migrant birds initiated their nocturnal
      activity punctually, and the time courses of the nocturnal activity of 88% of
      them revealed intra-individual stability over six consecutive nights. All birds
      initiated their nocturnal activity after sunset and civil twilight, and they were
      more active at the beginning than the middle or end of the night, suggesting that
      their drive to migrate could be synchronized with particular skylight conditions.
      For the first time, stable individual profiles in the daily time course of
      migratory restlessness are shown. These results support previous findings
      concerning biological rhythms of quail and raise questions concerning the timing
      of migratory behavior.

PMID- 17453847
TI  - Thermoregulatory and endocrine responses to light pulses in short-day acclimated
      social voles (Microtus socialis).
AB  - In mammals, nocturnal light pulses (NLP) have been demonstrated to affect
      physiology and behavior. However, the impact of NLP as a stressor has been less
      broadly examined. The purpose of this study was to examine the effect of NLP
      (three 15 min 450 lux light pulses) during each scotophase on both
      thermoregulation and endocrine stress responses under short-day (SD; 8L:16D)
      acclimation. Voles were acclimated to either SD (SD voles) or SD+NLP (NLP voles).
      Resistance to cold was estimated by measurements of body temperature (T(b))
      during cold exposure (5 degrees C). Daily rhythms of energy expenditure
      (calculated from oxygen consumption), urine production, and urinary adrenaline
      and serum cortisol levels were measured. T(b) values of SD voles were generally
      unaffected by the cold stimulus, whereas in NLP voles, resistance to cold was
      markedly lowered. While SD- and NLP voles showed similar ultradian
      characteristics in energy expenditure with a period of 3.5 h, mean energy
      expenditure levels were lowest for voles exposed to NLP-treatment. In SD voles,
      but not in NLP voles, urine production rates showed clear time variations and
      were consistently highest for SD voles, with significant differences during the
      scotophase. Both mean total urinary adrenaline and serum cortisol levels were
      significantly elevated in NLP-treated voles compared with the control group.
      Taken together, the results suggest that NLP negatively affects winter
      acclimatization of thermoregulatory mechanisms of M. socialis, probably by
      mimicking summer acclimatization, and consequently the thermoregulatory
      mechanisms respond inappropriately to ambient conditions. One important finding
      of this study is that NLP may act as a stressor and correspondingly impose a
      major threat to the physiological homeostasis of M. socialis, such that over
      winter survival might be compromised.

PMID- 17453848
TI  - Reproductive and post-embryonic daily rhythm patterns of the malaria vector
      Anopheles (Kerteszia) cruzii: aspects of the life cycle.
AB  - Females of Anopheles (Kerteszia) cruzii, a sporadic malaria vector in some areas
      of the Atlantic Forest in south and southeastern Brazil, were captured and
      studied under controlled conditions. In the laboratory, daily observations were
      conducted in natural light-dark cycles at 25.1+/-0.6 degrees C and relative
      humidity 57-81%. Post-embryonic development, which comprises four larval instars
      and the pupa, was continuously observed, and its cycles, as well as temporal
      components of reproduction, were registered. A preliminary study on female
      longevity was also performed. Oviposition, ecdysis from the third and fourth
      instars larvae, and pupation were visually monitored over three consecutive days
      and the emergence of adults over four consecutive days. Results were analyzed by
      circular statistics, and the null hypothesis of the absence of rhythm was
      assessed by Rayleigh's test at the 5% significance level. From a total of 141
      females captured, 113 (80.14%) survived and 79 (69.91%) were successfully fed on
      blood, offered at one of two time intervals, 09:00-10:30 h (morning) or 18:30
      20:00 h (evening). A total of 36 females laid 1063 eggs in 65 oviposition
      episodes, and 18 females presented fragmented oviposition. The average duration
      from egg-laying until adult emergence was 30.71+/-3.57 days, the larval stage
      being the longest in the post-embryonic development. Egg-laying showed a daily
      rhythm, with a peak at 23:24+/-3:47 h, 2 to 5 h after sunset. The time of the
      blood meal did not shift the phase of the egg-laying rhythm. The last larval
      ecdysis, pupation, and adult emergence did not follow a 24 h rhythmic pattern. A
      description of temporal patterns of post-embryonic development, particularly in
      the case of vectors, can be an important tool in research to determine methods of
      control.

PMID- 17453849
TI  - Temporal variations of coagulation factor VII activity in mice are influenced by
      lighting regime.
AB  - It was recently reported that the circadian clock machinery controls plasma
      levels of factor (F) VII, the serine protease triggering blood coagulation. Here,
      by exploiting the mouse model, this study showed that variations of photoperiod
      (i.e., winter or summer conditions or simulated chronic jetlag conditions) have a
      strong impact on plasma FVII activity levels. Under conditions mimicking summer
      or winter photoperiods, FVII activity showed a clear 24 h rhythmicity.
      Interestingly, mean daily FVII activity levels were significantly reduced in mice
      exposed to summer photoperiods. Behavioral activity rhythms under both
      photoperiods were synchronized to LD cycles, and the amount of activity per 24 h
      was comparable. The authors also investigated the influence of chronic jetlag
      (CJL) on the FVII activity rhythms, which can be easily mimicked in mice through
      continuous abrupt shifts in the lighting schedule. The exposure of mice to
      simulated CJL of either consecutive westward or consecutive westward and eastward
      flights for 15 days did not abolish the behavioral activity rhythms but was
      associated with a period significantly different from 24 h. Intriguingly, both
      types of CJL exerted a strong influence on FVII activity rhythms, which were
      virtually suppressed. Moreover, the mean daily FVII activity was significantly
      lower in the CJL than in the winter photoperiod condition. Taken together, these
      findings in mice provide novel insights into the modulation of FVII activity
      levels, which might have implications for human pathophysiology.

PMID- 17453850
TI  - Daily variations of homocysteine concentration may influence methylation of DNA
      in normal healthy individuals.
AB  - The regulation of genetic expression is tightly controlled and well balanced in
      the organism by different epigenetic mechanisms such as DNA methylation and
      histone modifications. DNA methylation occurring after embryogenesis is seen
      mainly as an irreversible event. Even small changes in genomic DNA methylation
      might be of biological relevance, and several factors influencing DNA methylation
      have been identified so far, one being homocysteine. In this study, genomic DNA
      methylation was analyzed and homocysteine plasma levels were measured over a 24 h
      period in 30 healthy students (15 males and 15 females) exposed to a standard 24
      h regime of daytime activity alternating with nighttime sleep. Plasma
      homocysteine concentrations were measured using HPLC detection. DNA was extracted
      from whole EDTA blood, and genomic DNA methylation was assessed by fluorescently
      labeled cytosine extension assay. Both homocysteine and DNA methylation showed 24
      h variation. Homocysteine showed a significant daily rhythm with an evening peak
      and nocturnal nadir in all subjects (p<0.001). Males showed higher overall
      homocysteine levels compared to females (p=0.002). Genomic DNA methylation showed
      a significant rhythm with increased levels at night (p=0.021), which was inverse
      to plasma homocysteine levels.

PMID- 17453851
TI  - Age-related differences in daily attention patterns in preschool, kindergarten,
      first-grade, and fifth-grade pupils.
AB  - The purpose of this study was to examine age-related differences in the daily
      attention patterns of preschool, kindergarten, first-grade, and fifth-grade
      pupils by means of a cross-sectional sample of 4-11-year-old French students. The
      importance of this study comes from the need to understand attention and apply
      the information it provides in educational settings. The first study conducted in
      a school setting with three age groups (4-5-, 6-7-, and 10-11-year-olds)
      demonstrated a rapid rhythmicity (60 minute period) for preschoolers (4-5 years
      old), with higher performance at the beginning of a teaching session. This
      pattern evolved until the fifth grade (10-11-year-olds), after which the temporal
      variation in attention was comparable to that of working adults, with
      fluctuations occurring on a half-day basis. The children's scores on crossing-out
      tests rose during the morning, declined in the early afternoon, and then rose
      again later during the afternoon. The second study enhanced our understanding of
      the change of the rhythm in attention of 4-7-year-old pupils. The rapid daily
      rhythmicity, linked to a session effect, seems to gradually disappear as children
      move from preschool 2 to kindergarten (4-5- to 5-6-year-olds) and then on to
      first grade (6-7-year-olds), where the daily attention patterns are closer to the
      standard pattern found by chronopsychology studies. The evolving patterns
      obtained from group means were confirmed by analysis of individual patterns.
      Exploratory statistical analysis of the data provided greater detail on the
      observed interindividual patterns, indicating that within each school grade, the
      attention patterns of some children are similar to the standard pattern while the
      attention patterns of others are more atypical. Deviations were mainly found in
      the 5-6-year-old age range (kindergarteners). The greatest 'mixture' of patterns
      was observed in the kindergartners (5-6-year-olds). Age plays a role not only in
      modifying daily changes but also in the distribution of interindividual
      differences in daily fluctuations, which occur most when children are of
      kindergarten age (5-6 years of age).

PMID- 17453852
TI  - Measuring activity patterns using actigraphy in multiple sclerosis.
AB  - Multiple sclerosis (MS) is a demyelinating disease resulting in impairments in
      motor and mental performance and restrictions in activities. Self-report
      instruments are commonly used to measure activity patterns; alternatively,
      actigraphs can be placed on several parts of the body. The aims of this study
      were to evaluate the superiority and specificity of actigraph placement (wrist
      vs. ankle) in subjects with MS and healthy controls and explore the relationship
      between self-report and objective activity patterns. A total of 19 subjects with
      definite MS and 10 healthy volunteers wore actigraphs on the non-dominant wrist
      and ankle for three days while they kept a log to register performed activities
      every .5 h. Wrist and ankle actigraphs produced similar activity patterns during
      the most active hours (09:00-20:30 h) (ANOVA, timexlocation interaction: F=.901,
      df=23, p=.597) in individuals with MS and healthy controls (between subjects
      factor F=3.275, p=.083). Wrist placement of the actigraphs was better tolerated
      than ankle placement. Wrist actigraph data corresponded to a higher degree with
      self-reported activities of the upper limbs in the early afternoon, whereas ankle
      data seem to reflect better whole body movements in the later afternoon/early
      evening. Overall, actigraph data correlated moderately with self-reported
      activity (r=.57 for ankle and r=.59 for wrist). The regression model revealed
      that self-reported activities explained 44% of the variance in ankle and 50% of
      wrist data. Wrist and ankle actigraphs produce similar activity patterns in
      subjects with MS and in healthy controls; however, the placement of actigraphs on
      the wrist is better tolerated. Ankle actigraphs reflect general movement but
      underestimate upper body activity. Subjective registration of activity level
      partly matches with objective actigraph measurement. A combination of both
      objective and subjective activity registration is recommended to evaluate the
      physical activity pattern of subjects with MS.

PMID- 17453853
TI  - Twenty-four-hour and annual variation in onset of epistaxis in Osler disease.
AB  - Osler disease is an autosomal dominant disorder of the fibrovascular tissue
      characterized by arteriovenous malformations with multi-systemic haemorrhages.
      Recurrent epistaxis is the predominant symptom in more than 90% of patients.
      Recent studies showed circadian and seasonal patterns in the onset of nosebleeds,
      similar to acute cardiovascular events, such as myocardial infarction and stroke.
      The aim of this study was to determine whether such patterns would also apply to
      the onset of epistaxis in patients with Osler disease. In all, 110 patients with
      Osler disease who were under treatment for recurrent epistaxis at the University
      Hospital of Mannheim were requested to complete a questionnaire addressing the
      intensity and frequency of epistaxis according to the classification of Bergler
      et al., as well as circadian and circannual rhythmicity in the occurrence of
      epistaxis according to visual analogue scales (VAS). More than half of the
      patients claimed to experience daily to weekly episodes of recurrent epistaxis.
      The occurrence of epistaxis showed a biphasic 24 h pattern, with a primary peak
      in the morning (05:00-8:00 h) and smaller secondary peaks in the evening (17:00
      20:00 h and 21:00-00:00 h). No significant seasonal variation was found in the
      onset of epistaxis. However, a slight tendency, with a peak in winter months, was
      observed. Similar to other chronobiological studies on nosebleeds, this study
      showed that the 24 h pattern and seasonal tendency in the onset of epistaxis even
      applied to patients with Osler disease. Further investigations are necessary to
      determine the pathological mechanism underlying this phenomenon.

PMID- 17453854
TI  - Possible linkage between the ability to change the period (tau) of the prolactin
      and cortisol rhythms in women and breast cancer risk.
AB  - The 24 h profiles of plasma hormone concentrations are rhythmic. The circadian
      period (tau) changes in development, with seasons, and in women with different
      stages of the menstrual cycle. It is known that the rhythms of prolactin and
      cortisol are sensitive to environmental time cues, such as changes in day length
      and phase; however, the importance of these changes is not yet understood. This
      study investigates whether there is a relation between the ability of a subject
      to respond to external cues that are associated with seasonal changes causing
      alteration of the rhythm's periods in cortisol and prolactin and the
      epidemiologically determined susceptibility to breast cancer. It is shown that
      the rhythmic output pattern of prolactin and cortisol in vivo is generated by
      more than one oscillator and structured by more than one rhythmic component. Each
      cohort of American women, classified on an epidemiologic basis as high risk (HR)
      or low risk (LR) to develop breast cancer, expresses different rhythmic output
      patterns of both variables, suggesting that the genetic background as defined by
      the risk state is related to differences in the circadian time structure,
      including the ability of the subject to change the rhythm's tau. The LR cohort
      exhibited a statistically significant change between seasons in the rhythm's tau
      of both the prolactin and cortisol patterns. In contrast, the HR cohort showed no
      change in the rhythm's tau between seasons for prolactin and cortisol patterns.
      These results show that in human beings, the presence of a circannual rhythm in
      the circadian time structure or the ability to adapt the circadian rhythmic
      pattern of these variables to external cues, such as seasons, is related to the
      partly genetically determined risk state to develop breast cancer and may be of
      importance for human health.

PMID- 17453855
TI  - The weight problem.

PMID- 17453856
TI  - Placebo, deceit and complementary/alternative medicine.

PMID- 17453857
TI  - Menopause and aging, quality of life and sexuality.

PMID- 17453858
TI  - Selective estrogen receptor modulators and risk for coronary heart disease.
AB  - Coronary heart disease (CHD) is the leading cause of death in women in most
      countries. Atherosclerosis is the main biological process determining CHD.
      Clinical data support the notion that CHD is sensitive to estrogens, but debate
      exists concerning the effects of the hormone on atherosclerosis and its
      complications. Selective estrogen receptor modulators (SERMs) are compounds
      capable of binding the estrogen receptor to induce a functional profile distinct
      from estrogens. The possibility that SERMs may shift the estrogenic balance on
      cardiovascular risk towards a more beneficial profile has generated interest in
      recent years. There is considerable information on the effects of SERMs on
      distinct areas that are crucial in atherogenesis. The complexity derived from the
      diversity of variables affecting their mechanism of action plus the differences
      between compounds make it difficult to delineate one uniform trend for SERMs. The
      present picture, nonetheless, is one where SERMs seem less powerful than
      estrogens in atherosclerosis protection, but more gentle with advanced forms of
      the disease. The recent publication of the Raloxifene Use for The Heart (RUTH)
      study has confirmed a neutral effect for raloxifene. Prothrombotic states may
      favor occlusive thrombi at sites occupied by atheromatous plaques. Platelet
      activation has received attention as an important determinant of arterial
      thrombogenesis. Although still sparse, available evidence globally suggests
      neutral or beneficial effects for SERMs.

PMID- 17453859
TI  - Recommendations from a multi-study evaluation of proposed criteria for staging
      reproductive aging.
AB  - In 2001, the Stages of Reproductive Aging Workshop (STRAW) proposed bleeding and
      endocrine criteria for defining the early and late menopausal transition stages.
      Based on expert consensus, STRAW recommended a shorter interval of amenorrhea
      than the commonly used 90-day amenorrhea criteria for late transition and a >7
      day change in cycle length for early transition. The ReSTAGE collaboration used
      prospective menstrual calendar data from four cohorts (TREMIN, Melbourne Women's
      Midlife Health Project, Seattle Midlife Women's Health Study, and Study of
      Women's Health Across the Nation) to quantitatively evaluate STRAW's
      recommendations. This empirical assessment supported the STRAW recommendations
      that (1) > or =60 days of amenorrhea be used to define the late menopausal
      transition and (2) that early transition is consistent with a persistent 7 or
      more day difference in length of consecutive cycles. Serum follicle stimulating
      hormone (FSH) values > or =40 IU/l was an independent marker of the transition
      and, when occurring together with a bleeding marker, increased prediction of
      final menstrual period. Such a FSH criterion could be incorporated into the STRAW
      paradigm to facilitate prediction of proximity of the final menstrual period.

PMID- 17453860
TI  - Ultra-low-dose estradiol and norethisterone acetate: effective menopausal symptom
      relief.
AB  - OBJECTIVE: To evaluate the efficacy of two ultra-low-dose 17beta-estradiol plus
      norethisterone acetate (NETA) treatment regimens for relieving menopausal
      symptoms. DESIGN: A total of 577 postmenopausal women were enrolled, in three
      treatment groups in a double-blind, randomized, placebo-controlled study of 0.5
      mg 17beta-estradiol + 0.1 mg NETA or 0.5 mg 17beta-estradiol + 0.25 mg NETA or
      placebo. Participants returned at weeks 4, 8, 12 and 24 for climacteric complaint
      evaluation based on a daily diary vasomotor symptom record. Patients were
      assessed by the Greene Climacteric Scale and urogenital symptoms were also
      evaluated. RESULTS: Treatment with ultra-low-dose 0.5 mg 17beta-estradiol + 0.1
      mg NETA (0.1 Group) or 0.5 mg 17beta-estradiol + 0.25 mg NETA (0.25 Group)
      effectively reduced the severity and number of hot flushes within the initial
      weeks of therapy. Compared to placebo, a rapid, statistically significant
      decrease in the frequency and severity of hot flushes was achieved by week 3,
      followed by further improvement which continued throughout the study. There were
      no statistically significant differences between the active treatment arms.
      CONCLUSIONS: The data show that both ultra-low-dose regimens are effective in
      reducing the severity and number of hot flushes compared to placebo, with good
      safety profiles.

PMID- 17453861
TI  - Correlates of sexual functioning among mid-life women.
AB  - OBJECTIVE: Studies have reported a decline in sexual functioning among women
      undergoing the menopausal transition. Few studies, however, have examined the
      associations between hormones and sexual dysfunction during this time period.
      Therefore, the purpose of this study was to examine the associations between
      participant characteristics and endogenous hormones with sexual functioning in
      mid-life women. METHODS: Data were analyzed from a community-based sample of 441
      women aged 45-54 years who stated that they were sexually active at the time of
      the study. Each participant completed a survey that included questions pertaining
      to sexual functioning and provided a blood sample that was used to measure
      estrogen and androgen concentrations. RESULTS: Among women who reported being
      sexually active, poorer self-reported health and the experiencing of depressive
      symptoms were significantly associated with not being satisfied with sexual
      relations after adjustment for other covariates. None of the hormones examined
      were significantly associated with overall sexual satisfaction. However,
      statistically significant associations between both total testosterone levels and
      the free testosterone index with satisfaction with the frequency of sexual
      relations were observed. CONCLUSIONS: Our findings indicate that the experiencing
      of depressive symptoms and the reporting of poor overall health are important
      correlates of sexual dysfunction. Further, our results suggest that higher total
      and free testosterone levels are significantly associated with a desire for
      increased frequency of sexual relations among mid-life women.

PMID- 17453862
TI  - Ultrasound appearance of the uterus in women over 60 years of age on tibolone: is
      it a SERM?
AB  - OBJECTIVES: To evaluate the effects of long-term tibolone on the endometria of
      asymptomatic women over the age of 60 years. METHODS: An observational study of
      the ultrasound appearance of the endometria of women aged 60 years or older
      taking long-term tibolone. Those found to have a double-layer endometrial
      thickness greater than 4 mm were offered endometrial biopsy. RESULTS: Seventeen
      asymptomatic patients with a mean age of 61 years (range 60-73 years) and an
      average duration of tibolone use of 5 years (range 3-12 years) were recruited.
      Seven patients (41%) showed a thickened endometrium of more than 4 mm. Three of
      these had an area of translucency in the subendometrial space. Of the ten women
      with an endometrial thickness of less than 4 mm, four showed the presence of
      subendometrial fluid. Hysteroscopy was performed in five out of the seven women,
      as two did not accept further investigations. In all five women, the endometrial
      cavity was reported as atrophic and the histology showed an inactive basal type.
      In two of the five cases examined histologically, there were additional changes
      suggesting endometrial polyp, although the samples were from macroscopically non
      polypoid endometrium. DISCUSSION: Endometrial thickness is increased in 41% of
      elderly women on long-term treatment with tibolone. However, at hysteroscopy, the
      endometrium was uniformly atrophic. Similar finding have been described in women
      using selective estrogen receptor modulators and a similar mechanism of action of
      these drugs on the uterus should be considered.

PMID- 17453863
TI  - The influence of smoking on uterine bleeding during sequential oral hormone
      therapy.
AB  - OBJECTIVE: To study the influence of smoking on uterine bleeding patterns during
      sequentially administered oral hormone therapy (HT). METHODS: Using a post-hoc
      strategy, we included four sequential oral HT groups from two studies. The
      therapies consisted of estradiol from days 1 to 28 (estradiol or estradiol
      valerate) and progestogen (levonorgestrel or gestodene) on days 17-28. A total of
      111 healthy, early postmenopausal women (38 smokers and 73 non-smokers) followed
      for 2 years were included in the analyses. Uterine bleeding data were collected
      from bleeding calendars. RESULTS: On the regimen containing levonorgestrel,
      smoking women had a cyclical bleeding significantly earlier than non-smoking
      women (about 2 days' difference). Moreover, smoking women had significantly
      longer bleeding than non-smoking women (about 1 day in difference). This was in
      contrast to the three regimens containing gestodene, where smoking seemed to have
      far less influence on uterine bleeding. CONCLUSIONS: On a regimen containing
      levonorgestrel, smokers exhibit an earlier and longer uterine bleeding than do
      non-smokers. This is in contrast to regimens containing gestodene, where smoking
      women are less likely to differ from non-smoking women with regard to bleeding.
      This indicates that smoking influences progestogen metabolism, and that this
      influence may vary with different progestogens. Further studies are needed.

PMID- 17453864
TI  - Testosterone addition during menopausal hormone therapy: effects on mammographic
      breast density.
AB  - OBJECTIVE: To study the effect on mammographic breast density of testosterone
      addition during combined estrogen/progestogen therapy in postmenopausal women.
      METHODS: A prospective, randomized, double-blind, placebo-controlled trial. A
      total of 99 women were given 2 mg 17beta-estradiol and 1 mg norethisterone
      acetate in combination with either a testosterone patch (300 mug/24 h) or a
      placebo patch. Mammographic breast density at baseline and after 6 months was
      assessed by visual classification scales and by digitized quantification. A
      standardized questionnaire was used to quantify subjective breast symptoms.
      RESULTS: Visual classifications showed an increase in mammographic density in 18
      30% of the women, with no significant differences between the treatment groups.
      The mean increase of the area of dense breast during treatment according to
      digitized assessment was 7.4% in the placebo group and 5.4% in the testosterone
      group. Breast symptoms showed a positive association with the increase in density
      (r(s) = 0.34; p < 0.01). Symptoms were most pronounced at 2 months of treatment.
      Density, both at baseline (r(s) = -0.35; p < 0.01) and change during treatment
      (r(s) = -0.28; p < 0.01) showed a negative association with free testosterone
      levels. CONCLUSION: The addition of testosterone does not appear to influence
      mammographic breast density in women concurrently treated with a common oral
      estrogen/progestogen regimen for a period of 6 months.

PMID- 17453865
TI  - The US National Cholesterol Education Programme Adult Treatment Panel III (NCEP
      ATP III): prevalence of the metabolic syndrome in postmenopausal Latin American
      women.
AB  - BACKGROUND: Metabolic syndrome (METS) is a strong predictor of cardiovascular
      risk. Since the prevalence of METS increases after menopause, gynecological
      routine consultation offers an excellent screening opportunity. OBJECTIVES: To
      assess the prevalence of METS in Latin American postmenopausal women and factors
      modifying its risk; as well as to assess the role of simple routine care
      measurements in the diagnosis of the METS. METHODS: A total of 3965
      postmenopausal women, aged 45-64 years, seeking health care at 12 gynecological
      centers in major Latin American cities were included in this cross-sectional
      study. The US National Cholesterol Education Programme Adult Treatment Panel III
      (NCEP ATP III) guidelines were applied to assess METS. This was present if three
      or more of the following conditions were present: waist circumference > or = 88
      cm; blood pressure > or = 130/85 mmHg; fasting plasma triglycerides > or = 150
      mg/dl; high density lipoprotein (HDL) cholesterol < 50 mg/dl; glucose > or = 110
      mg/dl or subjects were receiving treatment for their condition. RESULTS: The
      prevalences of having at least two, three, four or five components were 62.5,
      35.1, 13.5 and 3.2%, respectively. The prevalence increased from 28.1% in those
      aged 40-44 years to 42.9% in those aged 60-64 years. The risk of METS detection
      (multivariate analysis) increased with age (odds ratio (OR) 1.22, 95% confidence
      interval (CI) 1.03-1.43), time elapsed since menopause (OR 1.18, 95% CI 1.00
      1.38), smoking cigarettes (OR 1.40, 95% CI 1.19-1.65), obesity (OR 13.01, 95% CI
      10.93-15.49) and hypertension (OR 9.30, 95% CI 7.91-10.94). In contrast, hormone
      therapy reduces this risk (OR 0.59, 95% CI 0.51-0.70). CONCLUSION: There is a
      high prevalence of the metabolic syndrome in postmenopausal Latin American women
      seeking gynecologic health care. Age, years since menopause, obesity and
      hypertension are strong predictors of this condition.

PMID- 17453866
TI  - A prospective study of outcomes after hysterectomy in mid-aged Australian-born
      women.
AB  - OBJECTIVE: To describe the prevalence of hysterectomy in a mid-aged population
      based sample of Australian-born women who were menstruating at baseline and
      followed for 11 years, and to compare the hysterectomized women with the non
      hysterectomized women with regard to symptom reporting and health outcomes.
      METHODS: This was a 12-year prospective observational study of 438 women who at
      baseline were aged 45-55 years, not taking hormone therapy (HT) and had
      menstruated in the previous 3 months. Interviews were conducted face-to-face.
      RESULTS: After 11 years of follow-up, 39 (9%) women had experienced a
      hysterectomy, of whom 43.5% had the uterus only removed, 13% had the uterus plus
      one ovary and 43.5% had the uterus and both ovaries removed. Hysterectomies were
      performed on average 5.8 years prior to the year 11 interview. The mean age at
      hysterectomy was 54 years. Multivariate logistic regression analysis, including
      all co-variates, found that women who had experienced a hysterectomy (+/
      oophorectomy) were significantly more likely to complain of trouble sleeping (p <
      0.01), have problems with urine control (p < 0.05) and with their bowels (p =
      0.07), have used HT (p < 0.05) and have a higher body mass index (p < 0.05).
      There were no significant associations between hysterectomy and sexuality or hot
      flush reporting. CONCLUSION: In a community-based sample of Australian-born
      women, the experience of a hysterectomy after the age of 45 years was associated
      with bladder, weight and sleeping problems 5-6 years after the surgery.

PMID- 17453867
TI  - Linguistic characteristics of individuals with high functioning autism and
      Asperger syndrome.
AB  - This study examined the linguistic characteristics of high functioning
      individuals with autism and Asperger syndrome. Each group consisted of 10
      participants who were matched on sex, chronological age, and intelligence scores.
      Participants generated a narrative after watching a brief video segment of the
      Social Attribution Task video. Each participant was then asked 10 questions
      related to the stimulus video. The narrative samples and responses to the
      questions were analysed linguistically. Individuals with high functioning autism
      and Asperger syndrome performed similarly on most measures of language function;
      however, results suggest there may be pragmatically-based differences between the
      groups in the use of verb tense markers.

PMID- 17453868
TI  - Language development in a 3-year-old boy with Prader-Willi syndrome.
AB  - Prader-Willi syndrome (PWS) is a genetic disorder which has widespread
      developmental consequences including motor, cognitive and language delay.
      Previous research on PWS children has focused primarily on phonological
      development and dysfluency. In the present study, the lexical development of a
      boy with PWS was investigated in a series of 18 play sessions recorded over a 4
      month period from the ages 3;7 to 3;11. In comparison to the language development
      of children with Down syndrome this child with PWS appears to display a distinct
      developmental pattern. The possibility of detailing a behavioural phenotype of
      genetic disorders affecting language development is discussed.

PMID- 17453869
TI  - Crosslinguistic semantic and translation priming in normal bilingual individuals
      and bilingual aphasia.
AB  - The present study examined lexical representation in early Spanish-English
      bilinguals using an unmasked semantic and translation priming paradigm. In
      Experiment 1, participants were divided into two groups based on performance
      (more-balanced bilinguals, MB and less-balanced bilinguals, LB) on the
      experimental task. In Experiment 2, four patients with bilingual aphasia (BA)
      performed the same experiment. Results from both experiments revealed that all
      groups were more accurate for English targets (S-E direction) than Spanish
      targets (S-E direction). In Experiment 1, semantic priming was observed from
      English to Spanish in both the LB and MB groups although the effect was greater
      for the LB group. Further, only the LB group showed priming from Spanish to
      English. For both normal groups, there was no difference between translation and
      semantic priming effects. In Experiment 2, patients with bilingual aphasia
      demonstrated different patterns of activation with no clear trends. Two
      participants demonstrated greater priming from Spanish to English whereas two
      participants demonstrated the opposite effect.

PMID- 17453870
TI  - A preliminary study of speech discrimination in youth with Down syndrome.
AB  - Few studies have examined the ability of individuals with learning disabilities,
      in general, or with Down syndrome, specifically, to discriminate speech. The
      purpose of this study was compare the speech discrimination abilities of eight
      children with Down syndrome (aged 5.7 to 12.8 years) to seven nonverbal mental
      age matched controls (aged 4.0 to 5.3 years). A computer program presented the
      speech discrimination task using a two-cued alternative forced choice procedure.
      On each trial, the participants heard four successive synthesized speech
      syllables, with the first and last stimuli being the same and serving as the cue.
      The results indicated children with Down syndrome differed from their nonverbal
      mental-age matched peers in their ability to discriminate two of the five pairs,
      but not in the manner predicted. The relationship between speech discrimination,
      phonological memory, and speech-language development is also discussed.

PMID- 17453872
TI  - Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out
      of-hospital management.
AB  - A review of U.S. poison center data for 2004 showed over 12,000 exposures to
      tricyclic antidepressants (TCAs). A guideline that determines the conditions for
      emergency department referral and prehospital care could potentially optimize
      patient outcome, avoid unnecessary emergency department visits, reduce healthcare
      costs, and reduce life disruption for patients and caregivers. An evidence-based
      expert consensus process was used to create the guideline. Relevant articles were
      abstracted by a trained physician researcher. The first draft of the guideline
      was created by the lead author. The entire panel discussed and refined the
      guideline before distribution to secondary reviewers for comment. The panel then
      made changes based on the secondary review comments. The objective of this
      guideline is to assist poison center personnel in the appropriate prehospital
      triage and management of patients with suspected ingestions of TCAs by 1)
      describing the manner in which an ingestion of a TCA might be managed, 2)
      identifying the key decision elements in managing cases of TCA ingestion, 3)
      providing clear and practical recommendations that reflect the current state of
      knowledge, and 4) identifying needs for research. This guideline applies to
      ingestion of TCAs alone. Co-ingestion of additional substances could require
      different referral and management recommendations depending on their combined
      toxicities. This guideline is based on the assessment of current scientific and
      clinical information. The panel recognizes that specific patient care decisions
      may be at variance with this guideline and are the prerogative of the patient and
      the health professionals providing care, considering all the circumstances
      involved. This guideline does not substitute for clinical judgment.
      Recommendations are in chronological order of likely clinical use. The grade of
      recommendation is in parentheses. 1) Patients with suspected self-harm or who are
      the victims of malicious administration of a TCA should be referred to an
      emergency department immediately (Grade D). 2) Patients with acute TCA ingestions
      who are less than 6 years of age and other patients without evidence of self-harm
      should have further evaluation including standard history taking and
      determination of the presence of co-ingestants (especially other
      psychopharmaceutical agents) and underlying exacerbating conditions, such as
      convulsions or cardiac arrhythmias. Ingestion of a TCA in combination with other
      drugs might warrant referral to an emergency department. The ingestion of a TCA
      by a patient with significant underlying cardiovascular or neurological disease
      should cause referral to an emergency department at a lower dose than for other
      individuals. Because of the potential severity of TCA poisoning, transportation
      by EMS, with close monitoring of clinical status and vital signs en route, should
      be considered (Grade D). 3) Patients who are symptomatic (e.g., weak, drowsy,
      dizzy, tremulous, palpitations) after a TCA ingestion should be referred to an
      emergency department (Grade B). 4) Ingestion of either of the following amounts
      (whichever is lower) would warrant consideration of referral to an emergency
      department: an amount that exceeds the usual maximum single therapeutic dose or
      an amount equal to or greater than the lowest reported toxic dose. For all TCAs
      except desipramine, nortriptyline, trimipramine, and protriptyline, this dose is
      >5 mg/kg. For despiramine it is >2.5 mg/kg; for nortriptyline it is >2.5 mg/kg;
      for trimipramine it is >2.5 mg/kg; and for protriptyline it is >1 mg/kg. This
      recommendation applies to both patients who are naive to the specific TCA and to
      patients currently taking cyclic antidepressants who take extra doses, in which
      case the extra doses should be added to the daily dose taken and then compared to
      the threshold dose for referral to an emergency department (Grades B/C). 5) Do
      not induce emesis (Grade D). 6) The risk-to-benefit ratio of prehospital
      activated charcoal for gastrointestinal decontamination in TCA poisoning is
      unknown. Prehospital activated charcoal administration, if available, should only
      be carried out by health professionals and only if no contraindications are
      present. Do not delay transportation in order to administer activated charcoal
      (Grades B/D). 7) For unintentional poisonings, asymptomatic patients are unlikely
      to develop symptoms if the interval between the ingestion and the initial call to
      a poison center is greater than 6 hours. These patients do not need referral to
      an emergency department facility (Grade C). 8) Follow-up calls to determine the
      outcome for a TCA ingestions ideally should be made within 4 hours of the initial
      call to a poison center and then at appropriate intervals thereafter based on the
      clinical judgment of the poison center staff (Grade D). 9) An ECG or rhythm
      strip, if available, should be checked during the prehospital assessment of a TCA
      overdose patient. A wide-complex arrhythmia with a QRS duration longer than 100
      msec is an indicator that the patient should be immediately stabilized, given
      sodium bicarbonate if there is a protocol for its use, and transported to an
      emergency department (Grade B). 10) Symptomatic patients with TCA poisoning might
      require prehospital interventions, such as intravenous fluids, cardiovascular
      agents, and respiratory support, in accordance with standard ACLS guidelines
      (Grade D). 11) Administration of sodium bicarbonate might be beneficial for
      patients with severe or life-threatening TCA toxicity if there is a prehospital
      protocol for its use (Grades B/D). 12) For TCA-associated convulsions,
      benzodiazepines are recommended (Grade D). 13) Flumazenil is not recommended for
      patients with TCA poisoning (Grade D).

PMID- 17453873
TI  - Differences in treatment advice for common poisons by poisons centres--an
      international comparison.
AB  - OBJECTIVE: To investigate how poisons centres advise on management of common drug
      poisonings and compare advice on gut decontamination with the EAPCCT/AACT
      Position Statements. METHODS: An interactive questionnaire was sent to 14 poisons
      centres asking about working practices, "top 20" enquiries in 2002, and
      management of 4 specific drug poisonings. RESULTS: Replies were received from
      centres in 11 countries. Annual telephone enquiry numbers varied from 620 (Sri
      Lanka) to over 50,000 (Germany for 2000). Recommendations for gut decontamination
      for acetaminophen poisoning were: activated charcoal (AC) alone (5 centres);
      gastric lavage (GL) alone (1); AC and/or GL (3); AC, GL and/or ipecac (2). Only
      40% (4/10) recommended AC and 50% (3/6) GL within 1 hour. Intervention doses for
      gut decontamination ranged from 100-200 mg/kg (nine centres) and for "high-risk"
      groups 75-100 mg/kg (3). Plasma concentration for N-acetylcysteine (NAC)
      treatment ranged from 150 mg/L (four centres) to 200 mg/L (6) at 4 hours. Results
      were similarly varied for three other common drug poisons (benzodiazepines,
      amitriptyline, and paroxetine). CONCLUSIONS: Most poisons centres have protocols
      that differ in terms of gut decontamination, timing, and intervention doses. Many
      centres recommend charcoal or gastric lavage after the 1-hour limit proposed in
      the Position Statements. There is scope for rationalization of approaches to the
      management of common poisons.

PMID- 17453874
TI  - Exposure assessment of young children living in Chicago communities with historic
      reports of ritualistic use of mercury.
AB  - OBJECTIVE: According to a 1997 finding, mercury was available for sale in several
      Chicago communities for use in spiritual or medicinal practice. Mercury used this
      way may impact the health of children. The Chicago Department of Public Health
      (CDPH) and the Centers for Disease Control and Prevention conducted a study to 1)
      quantify mercury exposure in biological specimens collected from a pediatric
      clinic or home visit in selected neighborhoods in Chicago, and 2) investigate
      possible sources of mercury exposure in homes. METHODS: An exposure assessment
      study design was chosen to determine whether children living in Chicago
      communities that historically sold mercury were exposed to mercury vapor. We
      enrolled and collected biological samples from 306 children aged 2-10 years. In
      addition, we enrolled 42 children during a door-to-door survey of community
      residents. All the urine samples were analyzed for elemental or inorganic
      mercury. We also analyzed 43 blood samples to assess dietary mercury. RESULTS:
      Overall geometric mean urine mercury was 0.26 microg/L. Urine mercury levels did
      not differ among the three clinics or between the various participant groups. We
      did not find any association between ritualistic mercury use and exposure to
      mercury. CONCLUSIONS: Although pediatric mercury exposure does not appear to be
      problematic among our study population, mercury remains a potential health threat
      as long as it is readily available in communities. Healthcare providers should be
      aware of the potential for mercury exposure. Physicians and patients may call the
      National Poison Control Centers (1-800-222-1222) for information about diagnosis,
      testing, and treatment for all types of exposures, including exposure to mercury.
      Professionals are available 24 hours a day.

PMID- 17453875
TI  - Demand for poison control center services "surged" during the 2003 blackout.
AB  - BACKGROUND: Beginning 8/14/03, for 24 hours, the largest geographic power failure
      in U.S. history occurred. Our Poison Control Center (PCC) catchment area was one
      of the most severely affected, with most of the population left without
      electricity, fuel, water pressure, or municipal potable water. The paucity of
      reports on the impact of disasters on PCC operations led us to summarize our
      experience. METHOD: Data sources included 1) Toxicall human exposures during 8/03
      (with comparison to 2002 and to national trends) and 2) an after-action report
      completed by Specialists-in-Poison Information (SPI's) on duty during the
      disaster. RESULTS: The average call volume for 8/03 increased by 7.8%.
      Significant increases in human exposure and information calls occurred in four
      categories: gasoline, carbon monoxide, food poisoning, and water contamination.
      After-action report findings included: vulnerability of PCC operations to
      interruptions in power supply; lack of redundant communication methods; staffing
      challenges; and exclusion of PCC staff from hospital disaster plans despite co
      location. CONCLUSION: During the blackout of 2003, there was a measurably
      increased demand for poison center services. PCC disaster plans should address
      increased staffing needs during the time of disaster, communication system
      redundancy, back-up power supply, and SPI needs (food, water, transportation,
      environmental safety, and rest/rotation).

PMID- 17453876
TI  - Acute changes in sputum IL-10 following underground exposure to diesel exhaust.
AB  - INTRODUCTION: Although exposure to diesel exhaust has been linked with adverse
      health effects, little is known about the acute effects of exposure in the
      underground workplace. METHODS: Cross-shift spirometry and sputum induction were
      completed on twelve subjects associated with comminuted rock removal (mucking)
      operations in an underground copper mine using diesel powered and pneumatic
      equipment on separate days, and sputum collected on a baseline non-exposure day
      as well. RESULTS: For diesel operations, elemental carbon exposure averaged 538
      +/- 512 microg/m(3) during the 1-2 hour operations. Sputum interleukin-10
      decreased with diesel exhaust using one ELISA assay (3.69 v. 2.32 pg/ml, p =
      0.015), but increased when measured with a different ELISA kit (0.18 v. 0.59
      pg/ml, p = 0.019), consistent with an overall decline in IL-10 protein
      concentration but an increase in the biologically active form. Sputum interleukin
      6 decreased with exposure to diesel exhaust, although this change lost
      statistical significance when restricted to non-smokers. There were no
      significant changes in spirometry, interleukins 1beta, 4, and 8, tumor necrosis
      factor alpha or 8-hydroxy-2'-deoxyguanosine. CONCLUSION: High levels of diesel
      exhaust can result in rapid changes in sputum IL-10, suggesting possible protein
      modification.

PMID- 17453877
TI  - Physostigmine for gamma-hydroxybutyrate coma: inefficacy, adverse events, and
      review.
AB  - Physostigmine has been proposed as an antidote for gamma hydroxybutyrate (GHB)
      intoxication, based on associated awakenings in 1) patients anesthetized with GHB
      and 2) five of six patients administered physostigmine for GHB intoxication.
      However, there are neither well-supported mechanisms for physostigmine reversal
      of GHB effects, supportive animal studies, nor randomized, placebo-controlled
      trials demonstrating safety, efficacy, or improved outcomes. We sought to
      determine the outcomes of patients with GHB-induced coma after a physostigmine
      treatment protocol was instituted in an urban Emergency Department and ambulance
      service. Our search of medical records located five cases of GHB toxicity, all
      with co-intoxicants, who received physostigmine. None demonstrated response and,
      further, there were associated adverse events, including atrial fibrillation (2),
      pulmonary infiltrates (1) and significant bradycardia (1), and hypotension (1).
      We also reviewed 18 published GHB toxicity case series for incidence of adverse
      effects, stimulant co-intoxicants (which may heighten risk of physostigmine),
      complications, and outcomes of supportive care for GHB toxicity. We conclude that
      physostigmine is not indicated for reversal of GHB-induced alteration of
      consciousness; it is not efficacious, it may be unsafe, particularly in the
      setting of recreational polydrug use; and supportive care results in universally
      good outcomes.

PMID- 17453878
TI  - Increase of renal excretion of organo-mercury compounds like methlymercury by
      DMPS (2,3-Dimercapto-1-propanesulfonic acid, Dimaval).
AB  - In a highly mercury-burdened, small scale gold mining area in the Philippines,
      spontaneous urine samples were taken from 75 Hg intoxicated volunteers before
      (U1), and 2-3 hours after (U2) the oral application of 200 mg DMPS (2,3
      Dimercapto-1-propanesulfonic acid, Dimaval). In the urine samples, the
      concentrations of organic and inorganic bound mercury were determined separately
      by CV-AAS. In U1, median concentrations of 15.7 microg inorganic Hg/g crea. and
      2.2 microg organic Hg/g crea. were found. In U2, these values increased to 262
      for inorganic Hg and 14.5 for organic Hg. Maximum concentrations (microg/g crea.)
      as high as 7,593 for inorganic Hg and 2,011 for organic Hg were observed after
      DMPS. The mean (median) increasing factor (U2/U1) was 16.0 for inorganic Hg and
      5.1 for organic Hg. There was a trend that females responded better to DMPS than
      males. It was concluded that DMPS increases the renal excretion of organic bound
      Hg as it does for inorganic Hg, but to a lesser extent.

PMID- 17453879
TI  - Severe neurotoxicity associated with exposure to the solvent 1-bromopropane (n
      propyl bromide).
AB  - BACKGROUND: 1-bromopropane was recently substituted for traditional ozone
      depleting solvents in the industrial setting. CASE SERIES: We report a cohort of
      six cases of 1-bromopropane neurotoxicity occurring in foam cushion gluers
      exposed to 1-bromopropane vapors from spray adhesives. Patients 1-5 were exposed
      30-40 hours per week over three years; patient 6 had been employed for the
      previous three months. Exposure had peaked over the previous month when
      ventilatory fans were turned off. All patients complained of subacute onset of
      lower extremity pain or paresthesias. Five of six complained of difficulty
      walking and on examination had spastic paraparesis, distal sensory loss, and
      hyperreflexia. Three patients initially had nausea and headache. Serum bromide
      concentrations ranged from 44 to 170 mg/dL (reference 0-40 mg/dL). Apparent
      hyperchloremia was present with serum chloride concentrations of 105 to 139
      mmol/L (reference 98-107 mmol/L). Air samples taken at the workplace during
      gluing operations revealed the mean air concentration of 1-bromopropane to be 130
      ppm (range 91-176 ppm) with a seven hour time-weighted average of 108 ppm (range
      92-127 ppm), well above the EPA-proposed limit of 25 ppm. Two years after
      exposure, the two most severely affected patients had minimal improvement of
      function and they, with a third patient, continued to experience chronic
      neuropathic pain. CONCLUSION: This report supports the growing recognition of 1
      bromopropane neurotoxicity in humans consisting most commonly of headache,
      nausea, and subacute spastic paraparesis with distal sensory loss. The
      pathogenesis of 1-BP neurotoxicity in humans has yet to be fully elucidated but
      may reflect a central distal axonopathy syndrome.

PMID- 17453880
TI  - Zuclopenthixol-induced neuroleptic malignant syndrome in an adolescent girl.
AB  - We present the case of a 14-year-old female who had many characteristics of
      neuroleptic malignant syndrome (NMS) without pyrexia following a single depot
      injection of 200 mg of zuclopenthixol. The patient presented with a change in
      mental status that had progressed over the preceding 48 hours. Subsequently, she
      became increasingly agitated and confused, and developed diffuse muscular
      rigidity, mutism, tremor, tachycardia, diaphoresis, sialorrhea, and incontinence.
      Results of laboratory tests showed elevated CPK levels, leukocytosis, and a low
      serum iron level. Bromocriptine and diazepam were used as initial treatment of a
      probable NMS and provided significant improvement. During the next seven days,
      she clinically improved but continued to exhibit emotional lability, logorrhea,
      elevated mood, and increased psychomotor activity. Therefore, bromocriptine and
      diazepam were discontinued and lorazepam and lithium were administered as
      treatment of a bipolar disorder. Four weeks later, she was discharged in stable
      condition. The presentation of this case report suggests that the primary
      psychiatric diagnosis is important in antipsychotic usage in the pediatric
      population, and that young patients receiving neuroleptic treatment should be
      monitored for the early signs of NMS. Using the diagnostic criteria of a
      neuroleptic toxicity spectrum may result in greater clinical awareness and
      earlier recognition of NMS.

PMID- 17453881
TI  - Methemoglobinemia after ingestion of Chinese herbal medicine in a 9-day-old
      infant.
AB  - Traditional Chinese Medicine has long been popular among Chinese people, but it
      is always difficult for physicians to ascertain the nature and use of different
      ingredients involved. We report case of a 9-day-old infant who ingested home-made
      herbal medicine and developed cyanosis with methemoglobinemia. He responded to a
      single dose of methylene blue therapy. The suspected causative agent identified
      in the herbal medicine was sulfamethazine. This is the first reported case of
      methemoglobinemia related to the use of Chinese herbal medicine in the newborn
      period.

PMID- 17453882
TI  - Gastric stenosis in severe corrosive gastritis: prognostic evaluation by
      endoscopic ultrasonography.
AB  - INTRODUCTION: Endoscopic ultrasonography can provide high-resolution images of
      the gastric wall. CASE REPORT: A 24-year-old woman with severe corrosive
      gastritis following massive ingestion of an alkaline household chemical was
      examined with endoscopic ultrasonography using a 20-MHz probe. Endoscopic
      ultrasonography disclosed diffuse thickening of the entire gastric wall and lack
      of demarcation of the muscular layer in the antrum. Several weeks after the
      ingestion, stenosis developed in the antrum and was treated with laparoscopic
      gastrectomy. DISCUSSION: Endoscopic ultrasonography can provide accurate
      evaluation of depth of lesions in corrosive gastritis and may be useful in
      predicting gastric stenosis.

PMID- 17453883
TI  - Multi-organ toxicity and death following acute unintentional inhalation of paint
      thinner fumes.
AB  - BACKGROUND: Paint thinners containing a mixture of volatile organic solvents have
      considerable potential for solvent abuse. Deaths from solvent inhalation have
      been reported but most of them relate to intentional solvent abuse and occur soon
      after exposure. Accidental death due to unintentional inhalation of solvent
      vapors can also occur suddenly but more often, death results from late
      complications secondary to multi-organ toxicity. Malfunctioning of the
      cardiorespiratory, renal, and central nervous systems as a result of latent-toxic
      effects of solvent exposure has received little attention. CASE REPORT: An adult
      male unintentionally inhaled an excessive amount of paint thinner vapors and
      immediately developed central nervous system effects, followed by severe
      cardiorespiratory and renal pathologies that ultimately led to death 11 days
      after exposure. CONCLUSION: Acute unintentional inhalation of paint thinner fumes
      resulted in serious multi-organ toxicity and death. This case strongly suggests
      the need to employ suitable precautionary measures while handling volatile
      organic solvents in a confined area.

PMID- 17453884
TI  - A case series of xylometazoline overdose in children.
AB  - INTRODUCTION: Serious intoxications associated with low doses of imidazolines
      have been reported. Therefore, the treatment advice for children with
      xylometazoline overdose is usually to observe the child in the hospital, even
      after exposure to very low doses. Our aim was to determine the frequency of
      severe symptoms after xylometazoline exposure, and the systemic dose of
      xylometazoline below which asymptomatic children do not need to be hospitalized
      for observation. METHODS: From May 2002 until December 2004, we prospectively
      collected data on all consecutive cases of xylometazoline exposure in children <6
      years old reported to our poisons centre. Follow-up information was collected.
      The systemic dose was calculated and the frequency of severe symptoms was
      observed. RESULTS: During 32 months, we included 101 cases of xylometazoline
      exposure in children. For 63 out of these 101 cases, follow-up information could
      be collected. No severe symptoms were observed after exposure to xylometazoline
      doses reported to be below 0.4 mg/kg (95% confidence interval: 0-6%). CONCLUSION:
      We conclude that less than 6% of children exposed to xylometazoline, at doses
      reported to be less than 0.4 mg/kg body weight, may develop symptoms that require
      hospitalization.

PMID- 17453885
TI  - Confirmation of gestational exposure to alprazolam by analysis of biological
      matrices in a newborn with neonatal sepsis.
AB  - BACKGROUND: Different biological matrices are suitable for drug testing in
      newborns presenting with an acute withdrawal syndrome. CASE REPORT: The newborn
      of a mother reporting alprazolam use during pregnancy presented with respiratory
      distress and clinical features consistent with neonatal withdrawal syndrome or
      neonatal sepsis of vertical transmission. Alprazolam and its main metabolite
      (alpha-hydroxyalprazolam) were detected in cord serum, neonatal urine and also in
      neonatal hair, meconium and placenta, accounting for both acute and chronic
      exposure to this benzodiazepine during intrauterine life. At the same time, the
      clinical diagnosis of neonatal sepsis was confirmed by isolation of Streptococcus
      agalactiae from otic cultures. The infant received oxygen therapy and antibiotic
      treatment and recovered completely at the age of 11 days. Although no congenital
      anomalies or behavioral alterations were diagnosed during hospitalization,
      periodic follow-ups were requested to check for potential long-term effects of
      prenatal exposure to alprazolam.

PMID- 17453887
TI  - Acute amlodipine overdose treated by high dose intravenous calcium in a patient
      with severe renal insufficiency.
AB  - Calcium salts are frequently used in the treatment of calcium antagonist
      poisoning. Different dosing regimens have been employed. The major risk of high
      dose calcium therapy is iatrogenic hypercalcemia, especially in patients with
      diminished renal function. Repeated doses of calcium are therefore often avoided;
      however, inadequate use of intravenous calcium may cause treatment failure in
      severe calcium antagonist overdose. We report our experience of using high dose
      intravenous calcium chloride effectively and safely to treat severe amlodipine
      overdose in a patient with severe renal insufficiency.

PMID- 17453886
TI  - Abamectin intoxication with coma and hypotension.
AB  - Abamectin is a potent antihelmintic, insecticide, and miticide used to control
      pests of humans, veterinary animals, and crops. The toxic effects of abamectin
      are usually seen after oral ingestions. These are altered mental status,
      respiratory failure, and hypotension. We report a case of acute abamectin
      intoxication who presented with altered mental status to the emergency department
      after oral ingestion.

PMID- 17453888
TI  - Multiple organ failure following lamp oil aspiration.
AB  - CASE REPORT: A 26-month-old previously healthy boy of 15 kg was admitted to our
      hospital due to cyanosis following the aspiration of lamp oil. Aspiration
      resulted from the patient's father inducing emesis by digital stimulation of the
      boy's throat after the patient had ingested an unknown amount of lamp oil.
      Endotracheal intubation was done on the second hospital day in the Pediatric
      Intensive Care Unit (PICU) due to respiratory failure manifested by hypercapnia
      and hypoxemia. Mechanical ventilation, including high frequency oscillatory
      ventilation (HFOV) with iNO at 20 ppm, was started. However, he developed a
      spiked fever and developed an acute respiratory distress syndrome, a
      pneumothorax, and diffuse subcutaneous emphysema. His course was further
      complicated by anuric renal failure, rhabdomyolysis, severe hepatitis,
      pancytopenia, elevation of cardiac enzymes, and disseminated intravascular
      coagulation over the following days. He died on the ninth day of hospitalization
      because of multiorgan failure.

PMID- 17453889
TI  - Methanol poisoning with necrosis corpus callosum.

PMID- 17453890
TI  - Xylazine abuse: a rare cause of syncope.

PMID- 17453891
TI  - Comment on "Formation of methanol and formate in Wister rats after oral
      administration of methylated rapeseed oil: a fuel for lamps".

PMID- 17453893
TI  - Semantic-episodic interactions in the neuropsychology of disbelief.
AB  - INTRODUCTION: The purpose of this paper is to outline ways in which
      characteristics of memory functioning determine truth judgements regarding
      verbally transmitted information. METHOD: Findings on belief formation from
      several areas of psychology were reviewed in order to identify general principles
      that appear to underlie the designation of information in memory as "true" or
      "false". RESULTS: Studies on belief formation have demonstrated that individuals
      have a tendency to encode information as "true" and that an additional encoding
      step is required to tag information as "false". This additional step can involve
      acquisition and later recall of semantic-episodic associations between message
      content and contextual cues that signal that information is "false". Semantic
      episodic interactions also appear to prevent new information from being accepted
      as "true" through encoding bias or the assignment of a "false" tag to data that
      is incompatible with prior knowledge. CONCLUSIONS: It is proposed that truth
      judgements are made through a combined weighting of the reliability of the
      information source and the compatibility of this information with already stored
      data. This requires interactions in memory. Failure to integrate different types
      of memories, such as semantic and episodic memories, can arise from mild
      hippocampal dysfunction and might result in delusions.

PMID- 17453894
TI  - Intrusion errors in explicit memory: their differential relationship with
      clinical and social outcome in chronic schizophrenia.
AB  - INTRODUCTION: Memory deficits might account for clinical and adaptive differences
      between groups of patients with chronic schizophrenia. We investigated the
      qualitative factors of memory that influence clinical and social status. METHODS:
      Psychosocial functioning, clinical symptoms, and memory function were assessed in
      99 patients at four time points over a 16-month period using recall scores for
      semantically related words, unrelated words, paired associated learning, and word
      span. An initial cluster analysis using symptom assessment data from all four
      time points divided the sample into three groups: patients with low symptoms
      ratings that remained stable throughout the study period (low symptom-stable
      group - LSSG; N=51); patients with initially high symptoms ratings that
      subsequently improved (high symptom-improved group - HSIG; N=32); and patients
      with initially high symptoms ratings that deteriorated during the follow-up (high
      symptom-deteriorated group - HSDG; N=16). RESULTS: Memory was better preserved in
      LSSG compared to HSIG and HSDG patients. Recall performance was generally better
      for semantically related words than for unrelated words but the difference
      between LSSG and the two other groups was more constant over time for
      semantically related words. Extra-list errors variable was positively correlated
      with three PANSS measures (r=.25-.47). Also, the extra-list errors scores were
      correlated with the Magical Ideation Scale (r=.34-.39). Memory scores (global
      explicit, unrelated, related) were significantly and positively correlated with
      independent living skills (r=.26-.55) and the extra-list errors were negatively
      correlated with both social support and independent living skills (r=-.29 and r=
      .46, respectively). All groups showed a reduction in extraneous false recognition
      errors/intrusions (FRIs) over time with the HSIG showing the greater change. HSIG
      and HSDG patients committed slightly more FRIs in recall tasks (extraneous
      information) than LSSG patients. CONCLUSION: Memory performance is better in
      patients presenting with less severe symptomatology. The extent to which FRIs
      reduce over time in patients with schizophrenia is a novel finding.

PMID- 17453895
TI  - The Ambiguous Intentions Hostility Questionnaire (AIHQ): a new measure for
      evaluating hostile social-cognitive biases in paranoia.
AB  - INTRODUCTION: This study reports on the development of a new measure of hostile
      social-cognitive biases for use in paranoia research, the Ambiguous Intentions
      Hostility Questionnaire (AIHQ). The AIHQ is comprised of a variety of negative
      situations that differ in terms of intentionality. Items were developed to
      reflect causes that were ambiguous, intentional, and accidental in nature.
      METHODS: Participants were 322 college students who completed the AIHQ along with
      measures of paranoia, hostility, attributional style, and psychosis proneness.
      The reliability and validity of the AIHQ was evaluated using both correlational
      and multiple regression methods. RESULTS: The AIHQ had good levels of reliability
      (internal consistency and interrater reliability). The AIHQ was positively
      correlated with paranoia and hostility and was not correlated with measures of
      psychosis proneness, which supported the convergent and discriminant validity of
      the scale. In addition, the AIHQ predicted incremental variance in paranoia
      scores as compared to the attributional, hostility, and psychosis proneness
      measures. Ambiguous items showed the most consistent relationships with paranoia.
      CONCLUSIONS: The AIHQ appears to be a reliable and valid measure of hostile
      social cognitive biases in paranoia. Recommendations for using the AIHQ in the
      study of paranoia are discussed.

PMID- 17453896
TI  - An intersubjective perspective on negative symptoms of schizophrenia:
      implications of simulation theory.
AB  - The majority of neurocognitive models of negative symptoms in schizophrenia focus
      on failures to construct and sustain accurate representations of others and the
      world. Rarely considered are the intersubjective dimensions of negative symptoms
      as well as the mechanisms that sustain such symptoms. This paper critically
      analyses neurocognitive models of schizophrenia based on Theory of Mind (TOM)
      deficits and describes an alternative model of negative symptoms of schizophrenia
      based on Simulation Theory. We assert that several forms of negative symptoms of
      schizophrenia can be explained by an inability to express oneself, participate
      in, or be attuned to the context of social interactions. We label this deficit
      disadherence and suggest it may result from dysfunctions in "mirror" neurons. In
      particular, we suggest that patients with schizophrenia are unable to construct
      an inner model of the mind of another person and "select", from among various
      hypotheses, the one most suited to immediately understand the meanings and goals
      of interpersonal interactions. Moreover dysfunction in both "canonical" and
      "mirror" neurons, situated for the most part in the premotor and parietal cortex,
      could cause psychomotor negative symptoms. These hypotheses are explored in the
      context of a single case study.

PMID- 17453897
TI  - Memory and executive functions in adults with Gilles de la Tourette syndrome and
      chronic tic disorder.
AB  - INTRODUCTION: The main aim of the current study was to assess whether adults with
      either Tourette syndrome (TS) or chronic tic disorder (CTD) show a similar
      neuropsychological profile. Neuropsychological investigations of tic disorders
      have been mostly focused on children, mainly because symptoms peak during that
      period. Little has been carried out on adults, even if a significant proportion
      of the tic population experience moderate or marked levels of tic frequency
      throughout adulthood. Still, it is not clear whether neuropsychological
      performances are affected to the same degree in adults with TS and CTD. METHOD:
      Patients diagnosed with TS were compared with a CTD group and a control group
      free of psychiatric or neurological diagnosis, comparable in terms of age,
      gender, and intelligence. All participants completed two tests of memory (Rey
      Osterreich Complex Figure, California Verbal Learning Test), one test of motor
      dexterity (Purdue pegboard), and four tasks of executive function (Stroop, Color
      Trail Test, Tower of London, Wisconsin Card Sorting Test). RESULTS: TS and CTD
      patients showed nonverbal memory impairments while verbal memory and executive
      functioning remained intact. Results also indicated that nonverbal memory
      performances decrease as a function of tic severity. CONCLUSION: Both TS and CTD
      patients present a specific nonverbal deficit whilst the executive and motor
      functions are relatively intact. The two tic disorder subgroups might be part of
      a spectrum implicating mainly nonverbal memory.

PMID- 17453900
TI  - "Far from the heart far from the eye": evidence from the Capgras delusion.
AB  - INTRODUCTION: Capgras syndrome is characterised by the belief that a significant
      other has been replaced by an identical-looking impostor. These patients have no
      difficulties with visual recognition but fail to show a skin conductance response
      (SCR) to the objects of the delusion. A case of Capgras delusion (YY),
      specifically characterised by the absence of brain lesions, constituted a good
      opportunity to test the relationship between SCR hyporesponsiveness and eye
      movement patterns to familiar and unfamiliar faces. METHODS: Visual scan path and
      SCR were recorded for YY and 8 controls during the presentation of family
      members' photographs matched with unfamiliar faces of the same sex, age, and
      physical likeness. Eye movement patterns were explored by selecting three
      specific areas of interest (AOI) involving the eyes, the mouth, and the face
      regions. RESULTS: In contrast with controls, YY showed a reduction in number and
      sum of fixation durations to the eyes (p<.01) and no differential SCRs (p>.05) to
      familiar vs. nonfamiliar faces. SCR and fixation duration to family members' eyes
      were significantly correlated (r=.77) in both YY and controls. CONCLUSIONS: Eye
      region exploration seems to be related to the autonomic reactivity elicited by
      the affective valence of familiar faces.

PMID- 17453901
TI  - Emotion perception and social skill over the course of psychosis: a comparison of
      individuals "at-risk" for psychosis and individuals with early and chronic
      schizophrenia spectrum illness.
AB  - INTRODUCTION: Deficits in emotion perception and social skill have been well
      established in schizophrenia; however, little is known about the extent of these
      deficits across the course of the illness; that is, prior to illness onset and as
      the duration of the illness increases. METHOD: We compared emotion perception
      (i.e., the Face Emotion Identification Task [FEIT] and Face Emotion
      Discrimination Task [FEDT]; Kerr & Neale, 1993) and social skill (Conversation
      Probe role-play test) performance in four groups: individuals "at risk" for
      psychosis who met criteria for a prodromal state, individuals early in the course
      of a schizophrenia spectrum illness (SSI), individuals with a chronic SSI, and
      healthy control individuals. RESULTS: At-risk individuals did not significantly
      differ from control participants on emotion perception measures; however, early
      and chronic SSI groups performed significantly worse than controls, although not
      different from one another. Conversely, there was evidence that deficits in
      social skill are present prior to illness onset. Consistent with the findings for
      the emotion perception tasks, early and chronic SSI groups showed comparable
      levels of social skill impairment. CONCLUSION: Social skill deficits may be a
      vulnerability marker for schizophrenia, and it appears that the initial psychotic
      episode represents a critical point for the emergence of emotion perception
      deficits in schizophrenia spectrum illnesses.

PMID- 17453902
TI  - Delay discounting in schizophrenia.
AB  - BACKGROUND: It is well known that individuals with schizophrenia have
      dopaminergic abnormalities as well as memory-related difficulties, both of which
      are associated with impulsive decision making. We used a delay discounting
      measure to test the degree to which patients make future-oriented decisions.
      METHODS: 42 patients with schizophrenia and 29 healthy participants completed a
      delay discounting measure along with tests of cognitive function and, in
      patients, symptom ratings. RESULTS: Patients discounted more steeply than did
      comparison participants. Discounting among patients related to memory capacity
      and tended to relate inversely to negative symptoms. CONCLUSIONS: The impulsive
      decision making evidenced by patients suggests that they may be prone to choosing
      immediate over long-term rewards, even when their interests are better served by
      choosing the latter. Improving cognitive function may enhance their ability to
      make future-oriented decisions.

PMID- 17453903
TI  - Pseudoneglect in schizophrenia: a line bisection study with cueing.
AB  - INTRODUCTION: Numerous authors have reported the existence of lateralised
      abnormalities towards the right side in patients with schizophrenia. METHODS: In
      the present study, a manual line bisection task was used to assess the existence
      of a visuospatial bias in patients with schizophrenia as compared to healthy
      subjects and left unilateral neglect patients. In addition, we used a local
      cueing paradigm (consisting of a number placed on the right, on the left, or at
      both ends of the line). RESULTS: Healthy subjects showed a leftwards trend in the
      "no cue" condition (known as pseudoneglect) and neglect patients showed a right
      bias in all cue conditions. In contrast, patients with schizophrenia placed their
      manual estimation of the centre further to the left than healthy subjects in all
      cue conditions, reflecting neglect of the right side of the line. Moreover, like
      healthy subjects and neglect patients, patients with schizophrenia were affected
      by the local cueing. CONCLUSION: Hence, patients with schizophrenia show a bias
      in their spatial representation, which does not interfere with local context
      processing.

PMID- 17453904
TI  - Creative thinking in schizophrenia: the role of executive dysfunction and symptom
      severity.
AB  - INTRODUCTION: This study examines the notion of enhanced creative thinking in
      schizophrenia and determines the mediating role of executive dysfunction and
      symptom severity in this relationship. METHOD: Patients with chronic
      schizophrenia (n=28) were assessed on varied facets of creative cognition and
      standard tests of executive control relative to matched healthy control
      participants (n=18). RESULTS: Multivariate analyses revealed poorer performance
      by the patient group across almost all creative and executive function measures,
      except in the ability to be unconstrained by the influence of restrictive
      examples. Symptom-based contrasts using partial correlations revealed that
      differences were most extensive in the presence of thought disorder. Using
      hierarchical regression analyses, performance on the executive function tasks was
      found to play a mediatory role on specific aspects of creative cognition.
      CONCLUSIONS: Results are at odds with the popular notion of enhanced creative
      thinking in schizophrenia, but elucidate complex interactions between executive
      control and certain facets of creative thinking. In particular, performance of
      the schizophrenia group on measures that tap creativity elements of fluency and
      relevance were either partially or fully mediated by their performance on the
      executive control tasks, but this was not true of measures of originality.

PMID- 17453905
TI  - Emotional context processing is impaired in schizophrenia.
AB  - INTRODUCTION: Following considerable evidence for impaired context processing and
      facial emotion recognition in schizophrenia, this study examined the ability of
      schizophrenia patients to utilise contextual information when judging the meaning
      of facial expressions. METHODS: 22 healthy and 20 schizophrenia participants
      completed the "vignette-face" task (Carroll & Russell, 1996) in which target
      facial expressions are preceded by vignettes describing situational information
      that is discrepant in affective valence; judgements reflect either the dominance
      of the emotional context or the facial expression. Measures of basic facial
      emotion recognition and executive function were also obtained. RESULTS: On the
      vignette-face task, schizophrenia patients did not utilise contextual information
      for specific story-face pairs, whereas controls more commonly judged the emotion
      in line with contextual information. Most consistently, the responses of
      schizophrenia patients reflected neither situational nor facial cues when
      contextual cues suggested a complex mental state paired with a negative or threat
      related expression (e.g., anger, fear, sadness). Facial affect processing ability
      was a significant predictor of the successful social context integration in the
      vignette-face task. CONCLUSION: The reduced influence of context upon threat
      related expressions in schizophrenia may contribute to the misperception of
      threat in situations where contextual information should appease such an
      interpretation.

PMID- 17453907
TI  - Mechanical strain promotes fibroblast gene expression in presence of
      corticosteroid.
AB  - Posterior tibial tendon (PTT) dysfunction has commonly been treated with local
      corticosteroid injections to reduce inflammation. However, a concern with this
      treatment is potential degeneration and spontaneous rupture of the PTT. This
      study set out to determine whether mechanical strain may counteract the
      potentially deleterious effect of corticosteroid treatment on fibroblasts and
      therefore improve outcomes during recovery from tendinitis. In this study, PTT
      fibroblasts in vitro were treated with 0 M, 10(-7) M, 10(-6) M, and 10(-5) M
      triamcinolone acetonide (TA) while incubated under cyclic strains of 0% or 5% for
      24 hr. Type I collagen and decorin mRNA expressions were determined by RT-PCR.
      The results indicated that mechanical strain significantly increased type I
      collagen and decorin gene expression in the PTT fibroblasts and TA decreased type
      I collagen and decorin gene expression. Therefore, mechanical strain might be
      beneficial to PTT after corticosteroid treatment by direct stimulation of
      fibroblast synthesis.

PMID- 17453908
TI  - Comparison of nanoindentation measurements between osteogenesis imperfecta Type
      III and Type IV and between different anatomic locations (femur/tibia versus
      iliac crest).
AB  - Nanoindentation was used to compare the intrinsic mechanical properties of bone
      tissue (iliac crest biopsy) from children with type III and type IV osteogenesis
      imperfecta (OI). Young's modulus and hardness values were not significantly
      different between the two clinical severity groups on either cortical or
      trabecular measurement. In comparing the ratio of modulus over hardness (E/H)
      between OI type III and IV. The type III bone showed a marginally significant
      decrease for cortical bone and significant decrease for trabecular bone, which
      indicated that the OI type III bone was more brittle than OI type IV bone at the
      tissue level. In addition, nanoindentation measurements of the bone tissue
      harvested at femur/tibia from the same patients were compared with the results
      from the iliac crest biopsy. Young's modulus and hardness values were not
      significantly different between the two anatomic locations in either cortical or
      trabecular measurements. The ratio of E/H was not significantly different between
      the two groups. Results indicate that intrinsic modulus, hardness, and
      indentation deformation pattern (E/H) of OI bone tissues are not significantly
      different at long bone (midshaft of femur/tibia) and iliac crest. We observed
      that age (1.9 to 13.2 years) did not influence OI bone tissue intrinsic
      mechanical properties.

PMID- 17453909
TI  - Morphological changes in articular cartilage due to static compression: polarized
      light microscopy study.
AB  - We studied the deformation of the extracellular matrices in articular cartilage
      using a new compression-preservation method in histology. A Hoffman clamp was
      used to compress the tissue, which remained throughout the paraffin procedure and
      was removed from the embedded tissue block just before microtoming. Then 14
      cartilage-bone blocks from 2 canine humeri were compressed for various strain
      levels from 5% to 65%. The histological sections were studied using a polarized
      light microscope, which generated a pair of two-dimensional maps of the fibril
      orientation (angle) and fibril organization (retardance) for each section.
      Results were 3-fold. One there was little change in the angle and retardance
      profiles of the tissue for strain levels 0-15% and a significant change in these
      profiles for strain levels 15% and above. Two for higher compression, more
      fibrils became aligned parallel to the articular surface; and three at
      approximately 30% strain, a second "transitional zone" was formed in the deep
      part of the tissue. We concluded that this novel compression procedure can be
      used effectively to study the altered architecture of the collagen matrix in
      compressed cartilage.

PMID- 17453910
TI  - Biochemical characterization of collagen in alveolar mucosa and attached gingiva
      of pig.
AB  - Alveolar mucosa and attached gingiva are two continuous but functionally distinct
      connective tissues covering alveolar bone of the jaw. In this study, the major
      matrix component of these tissues, collagen, was biochemically characterized and
      compared. The tissues were obtained from mature pigs and analyzed for collagen
      content, amino acid composition, collagen types, collagen cross-linking, and gene
      expression. We found that alveolar mucosa is primarily composed of fibrillar
      collagens and the collagen content is higher than attached gingiva. The content
      of type III relative to type I collagen was higher in alveolar mucosa when
      compared with attached gingiva. The collagen cross-linking pattern also was
      distinct between the two tissues demonstrating that alveolar mucosa contained
      fewer reducible cross-links but more non-reducible cross-links in comparison to
      attached gingiva. The mRNA expression level of type I collagen in alveolar mucosa
      was significantly lower than that of attached gingiva. These results indicate
      that alveolar mucosa is a fibrillar collagen-rich tissue and, in comparison to
      gingival tissue, re-models slowly.

PMID- 17453911
TI  - Wound healing in tenascin-X deficient mice suggests that tenascin-X is involved
      in matrix maturation rather than matrix deposition.
AB  - Tenascin-X (TNX) is an extracellular matrix glycoprotein whose absence in humans
      leads to a recessive form of Ehlers-Danlos Syndrome (EDS). TNX deficient patients
      have hypermobile joints and fragile skin, but unlike the classical type of EDS,
      no atrophic scars were observed. Anecdotal evidence suggested that wound healing
      in TNX deficient patients is abnormal, but no detailed study has been performed
      so far. To address the role of TNX in wound healing, we analyzed skin wound
      morphology and mechanical properties of scars in TNX knockout (KO) mice. Breaking
      strength of unwounded skin of KO mice is significantly lower (<50%) than that of
      wild-type (WT) mice. In the early stage of wound healing when TNX is hardly
      expressed in WT wounds (day 7), WT and KO skin are of similar strength. After 14
      days, when TNX starts to be expressed at moderate levels in wounds of WT mice,
      the WT scars gain a further increase in breaking strength, whereas KO scars do
      not progress beyond the mechanical strength of uninjured KO skin. No obvious
      differences between KO and WT mice were noted in the rate of wound closure, or in
      expression of fibrillar collagens during wound healing. We conclude that TNX is
      unlikely to be involved in matrix deposition in the early phase of wound healing,
      but it is required in the later phase when remodeling and maturation of the
      matrix establishes and improves its biomechanical properties.

PMID- 17453912
TI  - Distribution of collagen types I, III, and V in pregnant mouse endometrium.
AB  - Decidualization in mice comprises a deep remodeling of extracellular matrix (ECM)
      components of the endometrium. In a previous biochemical study we showed that
      collagen types I and III are present in both pregnant and nonpregnant mouse
      endometrium, whereas collagen type V is expressed exclusively after the onset of
      decidualization. The distribution of collagen types in the pregnant mouse
      endometrium and possible changes of these molecular types in the different
      regions of the decidua is, however, not known. Using immunofluorescence and
      confocal microscopy we showed the presence of collagen types I, III, and V in the
      endometrial stroma of implantation and interimplantation sites from days 5 to 8
      of pregnancy in the mouse. Collagen type III was chiefly expressed in the
      implantation sites and was the only collagen type to be present in the materno
      fetal interface on the day of the embryo implantation. However, collagen type I
      was the predominant collagen in the interimplantation sites. Collagen type V was
      weakly expressed in the nondecidualized stroma during all periods but was
      expressed in larger amounts in the decidualized areas on day 7 of pregnancy,
      simultaneously with the accumulation of thick collagen fibrils in the same
      region. The highest immunofluorescence labeling for the three types of collagen
      was observed on day 7 when the antimesometrial decidual tissue achieved its
      greatest development. These data support previous studies that showed an intense
      ECM remodeling of the mouse endometrial stroma during the beginning of pregnancy.
      This outstanding remodeling may be important to stabilize placental anchorage.

PMID- 17453914
TI  - JSCTR-CTR Commentary by Toshihiko Hayashi.

PMID- 17453916
TI  - Nucleases of the metallo-beta-lactamase family and their role in DNA and RNA
      metabolism.
AB  - Proteins of the metallo-beta-lactamase family with either demonstrated or
      predicted nuclease activity have been identified in a number of organisms ranging
      from bacteria to humans and has been shown to be important constituents of
      cellular metabolism. Nucleases of this family are believed to utilize a zinc
      dependent mechanism in catalysis and function as 5' to 3' exonucleases and or
      endonucleases in such processes as 3' end processing of RNA precursors, DNA
      repair, V(D)J recombination, and telomere maintenance. Examples of metallo-beta
      lactamase nucleases include CPSF-73, a known component of the
      cleavage/polyadenylation machinery, which functions as the endonuclease in 3' end
      formation of both polyadenylated and histone mRNAs, and Artemis that opens DNA
      hairpins during V(D)J recombination. Mutations in two metallo-beta-lactamase
      nucleases have been implicated in human diseases: tRNase Z required for 3'
      processing of tRNA precursors has been linked to the familial form of prostate
      cancer, whereas inactivation of Artemis causes severe combined immunodeficiency
      (SCID). There is also a group of as yet uncharacterized proteins of this family
      in bacteria and archaea that based on sequence similarity to CPSF-73 are
      predicted to function as nucleases in RNA metabolism. This article reviews the
      cellular roles of nucleases of the metallo-beta-lactamase family and the recent
      advances in studying these proteins.

PMID- 17453917
TI  - Molecular chaperones HscA/Ssq1 and HscB/Jac1 and their roles in iron-sulfur
      protein maturation.
AB  - Genetic and biochemical studies have led to the identification of several
      cellular pathways for the biosynthesis of iron-sulfur proteins in different
      organisms. The most broadly distributed and highly conserved system involves an
      Hsp70 chaperone and J-protein co-chaperone system that interacts with a scaffold
      like protein involved in [FeS]-cluster preassembly. Specialized forms of Hsp70
      and their co-chaperones have evolved in bacteria (HscA, HscB) and in certain
      fungi (Ssq1, Jac1), whereas most eukaryotes employ a multifunctional
      mitochondrial Hsp70 (mtHsp70) together with a specialized co-chaperone homologous
      to HscB/Jac1. HscA and Ssq1 have been shown to specifically bind to a conserved
      sequence present in the [FeS]-scaffold protein designated IscU in bacteria and
      Isu in fungi, and the crystal structure of a complex of a peptide containing the
      IscU recognition region bound to the HscA substrate binding domain has been
      determined. The interaction of IscU/Isu with HscA/Ssq1 is regulated by HscB/Jac1
      which bind the scaffold protein to assist delivery to the chaperone and stabilize
      the chaperone-scaffold complex by enhancing chaperone ATPase activity. The
      crystal structure of HscB reveals that the N-terminal J-domain involved in
      regulation of HscA ATPase activity is similar to other J-proteins, whereas the C
      terminal domain is unique and appears to mediate specific interactions with IscU.
      At the present time the exact function(s) of chaperone-[FeS]-scaffold
      interactions in iron-sulfur protein biosynthesis remain(s) to be established. In
      vivo and in vitro studies of yeast Ssq1 and Jac1 indicate that the chaperones are
      not required for [FeS]-cluster assembly on Isu. Recent in vitro studies using
      bacterial HscA, HscB and IscU have shown that the chaperones destabilize the
      IscU[FeS] complex and facilitate cluster delivery to an acceptor apo-protein
      consistent with a role in regulating cluster release and transfer. Additional
      genetic and biochemical studies are needed to extend these findings to mtHsp70
      activities in higher eukaryotes.

PMID- 17453918
TI  - The epidemiology of childhood leukemia with a focus on birth weight and diet.
AB  - Leukemia is the most common childhood cancer and a major source of morbidity and
      mortality. The etiology of childhood leukemia remains largely unknown.
      Cytogenetic abnormalities determine disease subtypes, prognosis, clinical
      presentation, and course and may help in discovering etiological factors.
      Epidemiologic investigations of leukemia are complicated by many factors,
      including the rarity of the disease, necessitating careful study design. Two
      emerging areas of interest in leukemia etiology are birth weight and diet. High
      birth weight has been associated with increased risk of childhood leukemia. The
      biological mechanism behind this association may involve insulin-like growth
      factor I (IGF-I), which is associated with high birth weight. IGF-I may act by
      increasing the absolute number of stem cells available for transformation,
      stimulating the growth of cells that are already transformed, or a combination of
      effects. Diet has been linked with leukemia. Maternal dietary DNA topoisomerase
      II (DNAt2) inhibitor intake is associated with infant acute myeloid leukemia
      (AML) with the MLL gene translocation. Increased intake of fruits and vegetables
      has been associated with decreased leukemia risk and, relatedly, lack of maternal
      folate supplementation has been associated with increased childhood leukemia
      risk, possibly by causing DNA hypomethylation and increased DNA strand breaks.
      Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms modify this risk.

PMID- 17453919
TI  - Precursor lesions of prostate cancer.
AB  - Several morphological lesions have been proposed that may act as potential
      precursor lesions of prostate cancer. These are the morphologically distinct
      entities of focal atrophy or post-atrophic hyperplasia (PAH), atypical
      adenomatous hyperplasia (AAH) or adenosis, and prostatic intraepithelial
      neoplasia (PIN). The diagnostic criteria of low-and high-grade PIN (LGPIN and
      HGPIN, respectively) and of lesions suspicious for cancer (LSC) have been
      established. In the present review, we present the current knowledge about the
      precursor lesions of prostate cancer. We focus on the epidemiology, pathogenesis,
      clinical markers, and differential diagnosis of PIN. The similarities between
      HGPIN and prostate cancer are also discussed. Furthermore, potential markers and
      management strategies (that is, repeat biopsy, chemoprevention, radical
      prostatectomy, radiotherapy) are outlined along with updated recommendations.

PMID- 17453920
TI  - Antiphospholipid antibodies: laboratory and pathogenetic aspects.
AB  - Antiphospholipid antibodies (aPL) constitute a heterogeneous group of
      autoantibodies that share the ability to bind phospholipids (PL) alone, protein
      PL complexes, or PL-binding proteins. They have been detected in isolation, in
      association with autoimmune diseases such as systemic lupus erythematosus (SLE),
      and during the course of different infections. aPL have been associated with an
      array of clinical manifestations in virtually every organ, although deep vein and
      arterial thrombosis as well as pregnancy morbidity are predominant. The co
      occurrence of these clinical findings with aPL constitutes the so-called
      antiphospholipid syndrome (APS). aPL can be detected by immunological methods
      [e.g., anticardiolipin antibodies (aCL)] or by functional methods that exploit
      the effect of aPL on blood coagulation [lupus anticoagulant (LA)]. Since aPL are
      heterogeneous, numerous immunological and coagulation assays have been developed.
      These assays have not been fully standardized, and, therefore, problems such as
      high interlaboratory variation are relatively frequent. Recently, recommendations
      have been published regarding LA and aCL testing. Not all aPL are pathogenic.
      However, when they are not associated with infections, they have a role in the
      pathogenesis of APS. Clinical and experimental data have shown that aPL exert
      their pathogenic activity by interfering with the function of coagulation
      factors, such as thrombin and factors X, XI and XII, and with the function of
      anticoagulant proteins of the protein C system. In addition, aPL interaction with
      platelets and endothelial cells induces a pro-adhesive activated phenotype.

PMID- 17453921
TI  - Olive oil waste treatment: a comparative and critical presentation of methods,
      advantages & disadvantages.
AB  - Since olive oil industries were considered responsible for a great amount of
      pollution there has been a strong need for optimization of olive oil waste
      treatment systems. The currently employed systems are numerous and fall in the
      following large categories; bioremediation (ex-situ, in-situ), thermal processes
      (incineration, pyrolysis, gasification), evaporation, membrance processes,
      electrolysis, ozonation, digestion, coagulation/flocculation/precipitation, and
      distillation. Both advantages and disadvantages in conjunction with respective
      methodology and explicit flow diagrams were presented per waste treatment method.
      Furthermore, most recent studies were reported and more than twenty-five figures
      showing mainly the effectiveness of the current waste treatment methods versus
      time or temperature were displayed. The comparative presentation of the various
      olive oil waste treatment methodologies showed that though bioremediation stands
      for the most enviromentally friendly technique, its required longer treatment
      time in conjuction with its weakness to deal with elemental contaminants makes
      imperative the employment of a second alternative technique which could either be
      a membrance process (low energy cost, reliability, reduced capital cost) or a
      coagulation/flocculation method because of its low cost and high effectiveness.
      Biogas production appears to be another promising and energy effective waste
      treatment method. On the other hand, methods like distillation and ozonation
      (high cost) and electrolysis (experimental level) are unlikely to dominate this
      field unless their high cost is substantially reduced in the near future.

PMID- 17453922
TI  - Saponins: properties, applications and processing.
AB  - Saponins are a diverse group of compounds widely distributed in the plant
      kingdom, which are characterized by their structure containing a triterpene or
      steroid aglycone and one or more sugar chains. Consumer demand for natural
      products coupled with their physicochemical (surfactant) properties and mounting
      evidence on their biological activity (such as anticancer and anticholesterol
      activity) has led to the emergence of saponins as commercially significant
      compounds with expanding applications in food, cosmetics, and pharmaceutical
      sectors. The realization of their full commercial potential requires development
      of new processes/processing strategies to address the processing challenges posed
      by their complex nature. This review provides an update on the sources,
      properties, and applications of saponins with special focus on their extraction
      and purification. Also reviewed is the recent literature on the effect of
      processing on saponin structure/properties and the extraction and purification of
      sapogenins.

PMID- 17453923
TI  - Food fortification strategy--preventing iron deficiency anemia: a review.
AB  - Iron deficiency anemia (IDA) is a significant challenge in developing countries.
      It increases the risk of premature delivery and low birth weight. In children,
      IDA retards growth, impairs cognitive performance, and reduces physical activity.
      It also accelerates the mortality and morbidity rate in women. The key factors
      responsible include dietary elevated iron demand, socioeconomic, and disease
      status. To overcome IDA, disease control measures, dietary diversification,
      supplementation and iron fortification in food have been adopted. Iron
      fortification in food is considered a long term and sustainable strategy in the
      present scenario. For an efficient fortification program, the combination of iron
      fortificants and food vehicle must be safe, acceptable, and consumed by the
      target population. Moreover, it should not adversely affect acceptability and
      stability of the end product.

PMID- 17453924
TI  - Food supplements and European regulation within a precautionary context: a
      critique and implications for nutritional, toxicological and regulatory
      consistency.
AB  - In this paper, we review European legislation in the field of micronutrient food
      supplements and find it wanting. It is shown that the precautionary principle,
      embedded in European food legislation, pre-empts innovative developments in this
      field. In view of the scientific advances in micronutrients research, we
      subsequently critique the precautionary perspective and propose a novel outlook
      on micronutrients food supplements regulation. However, this requires a
      transition from the "survival" approach of the current deficiency-related RDAs to
      a "health-optimization" approach of a n(ew)-RDA. Genomic integrity is central in
      this envisioned transition.

PMID- 17453925
TI  - Impact of oil used by the frying industry on population fat intake.
AB  - Chronic multifactorial diet related diseases are the major causes of death and
      illness worldwide. The amount and composition of fat in the diet is an important
      determinant of the pathobiology of many of these conditions. In the current
      review the associations between dietary fat and disease risk will be considered.
      Mean population fat intakes will be compared with dietary recommendations aimed
      at reducing the population burden of disease and the main sources of fat in the
      adult and childhood diet will be given. An assessment will be made of the
      principal vegetable oil sources used in the manufacture of processed foods, in
      particular fried foods, with particular reference to the rheological and
      nutritional justification for their use. The impact of the more widespread use of
      alternative oil sources with improved fatty acid profiles, on the fat composition
      of fried foods and the overall diet will be presented, demonstrating that such
      apparently focussed approaches could potentially result in a significant impact
      on population fat intake and potentially overall chronic disease burden.

PMID- 17453926
TI  - Role of physical structures in bulk oils on lipid oxidation.
AB  - Lipid oxidation is important to food manufacturers especially when they increase
      unsaturated lipids in their products to improve nutritional profiles.
      Unfortunately, the number of antioxidants available to food manufacturers to
      control oxidative rancidity is limited and the approval of new antioxidants is
      unlikely due to economic barriers in obtaining government approval for new food
      additives. Therefore, new antioxidant technologies are needed for food oils. This
      paper reviews the current knowledge of lipid oxidation in foods with emphasis on
      how physical properties of food systems impact oxidation chemistry. In
      particular, the role of association colloids in bulk oils on lipid oxidation
      chemistry is discussed in an attempt to understand mechanisms of oxidation.
      Increasing the understanding of how physical properties impact lipid oxidation
      could lead to the development of novel antioxidant technologies that not only
      protect the oil against oxidation and increase shelf-life but also allow food
      manufacturers to include more nutritionally beneficial fatty acids in their
      products.

PMID- 17453927
TI  - Discoloration in raw and processed fruits and vegetables.
AB  - Discoloration in fruits and vegetables is reviewed in relation to the chemical
      and biochemical causes of black, brown, red, yellow, and green discolorations. In
      raw materials, only a limited understanding has so far been achieved of the
      internal black and brown discolorations. The biochemical signaling pathways
      triggered by wounding or chilling-storage, the nature of the enzymes and reactive
      oxygen species involved, and the identity of the phenolic compounds oxidized are
      areas where further information is desirable. In processed materials, a greater
      comprehension is needed of the role of ascorbic acid reactions in the browning of
      fruits and "pinking" of Brassicaceous vegetables, and more information is
      desirable on the structure and properties of the discoloring pigments in many
      products. It is concluded that a greater knowledge of these areas, and of the
      naturally-occurring constituents that can accelerate or inhibit the causative
      reactions, would lead to the development of more efficient methods of controlling
      fruit and vegetable discolorations.

PMID- 17453928
TI  - Regulation of sugar catabolism in Lactococcus lactis.
AB  - The increasing number of genomic and post-genomic studies on Gram-positive
      organisms and especially on lactic acid bacteria brings a lot of information on
      sugar catabolism in these bacteria. Like for many other bacteria, glucose is the
      most preferred source of carbon and energy for Lactococcus lactis. Other carbon
      sources can induce their own utilization in the absence of well-metabolized
      sugar. These processes engage numbers of genes and undergo complex mechanisms of
      regulation. In this review, we discuss various biochemical and genetic control
      mechanisms involved in sugar catabolism, like regulation by repressors,
      activators, antiterminators or carbon catabolite repression control.

PMID- 17453929
TI  - Leprosy and tuberculosis: an insight-review.
AB  - A quick glance at this review article provides an insight into the common and
      different features of M. leprae and M. tuberculosis and the diseases caused by
      these organisms. Table I provides the popular names, history, stigma, description
      of the disease, clinical features, classification and the types of disease
      manifestations, who are affected, Signs and Symptoms, Clinical examination,
      treatment regimens, reactions, relapses, immunity, infectiousness, risk groups,
      deformities, sequelae, transmission, prevention, complications, vaccination,
      laboratory studies, days of importance for both the diseases. Table II provides
      information regarding the causative organisms, M. leprae and M. tuberculosis,
      their size, genome, protein coding region, lost genes, pseudogenes,
      classification, predilection, incubation period, ecology, cell structure,
      metabolism, resistance, bacterial index, growth in vitro, experimental animals,
      etc. Table III provides figures of M. leprae and M. tuberculosis, their genome,
      Lepromin and Tuberculin testing, Global scenario, Indian scenario, colonies of M.
      leprae and M. tuberculosis, drugs for treatment of tuberculosis and leprosy (MDT
      blister pack), and so on.

PMID- 17453930
TI  - The non-O157 shiga-toxigenic (verocytotoxigenic) Escherichia coli; under-rated
      pathogens.
AB  - Following a brief review of the ecology of Escherichia coli in general, the role
      of Shiga-Toxigenic (Verocytotoxigenic) E. coli (STEC) as pathogens is addressed.
      While STEC belonging to the serogroup O157 have been extensively studied and
      shown to be involved in many cases and outbreaks of human disease, the importance
      of STEC belonging to other serogroups has not been recognized as much. This
      review addresses the problems associated with these pathogens, demonstrating that
      increasing the awareness of them is a major part of the problem. This review then
      demonstrates how widespread isolations especially from food animals and human
      disease have been, discussing in particular STEC belonging to serogroups O8, O26,
      O103, O111, O113 and O128. The animal host-specificity of these STEC is also
      reviewed. In conclusion some methods of improving isolation of these pathogens is
      addressed.

PMID- 17453931
TI  - Issues for microbial regulation: Aeromonas as a model.
AB  - The decision by public health agencies to regulate specific microorganisms that
      may be found in drinking water can only be made if specific criteria find that a
      microorganism poses a health risk. These criteria should include: (1) there is a
      clinical history of an organism causing disease from the ingestion of drinking
      water; (2) there is epidemiological evidence that drinking water rather than food
      or other vectors is a major source of disease; (3) there is sufficient evidence
      that the target organism, if found in water, possesses virulence factors capable
      of causing disease in humans; (4) there is sufficient evidence that the target
      organism is not readily removed or inactivated by multi-barrier conventional
      water treatment process (e.g., coagulation-filtration-disinfection); (5) there is
      sufficient evidence that the target organism, if surviving conventional
      treatment, will be viable, virulent, and present in sufficient numbers to cause
      disease; (6) there are robust analytical methods for the target organism which
      have acceptable sensitivity, specificity, and reproducibility to measure
      accurately the presence of the target organism in treated water; and (7) the
      performance criteria of analytical method(s) for the target organism have been
      certified by the appropriate public health agency, and there is intra-laboratory
      field-test performance data to base this certification.

PMID- 17453932
TI  - Aromatic amines in experimental cancer research: tissue-specific effects, an old
      problem and new solutions.
AB  - Carcinogenic aromatic amines usually produce tumors in specific target tissue,
      such as 2-acetylaminofluorene (AAF) producing liver tumors in rats, in contrast
      to some other structurally related arylamines. A hypothesis is presented that
      explains the mode of action in this rat liver model. Genotoxic and nongenotoxic
      effects work together and make AAF a complete rat liver carcinogen. The
      cytotoxic, promoting effects are particularly important. N-Hydroxy-2
      aminofluorene and 2-nitrosofluorene, two metabolites of AAF, are able to uncouple
      the mitochondrial respiratory chain. They entertain a redox cycle that removes
      electrons from the respiratory chain and impairs ATP production. The dose
      dependent opening of the mitochondrial permeability transition pore signals the
      viability of the cell. If the pore is opened to a certain extent, the cell is
      eliminated by apoptosis. As a consequence, oval cells proliferate, and as this
      process is overloaded, the liver transforms into a cirrhosis-like situation and
      thus provides the conditions under which initiated liver cells develop tumors.
      Such an interpretation is based on assumptions that have been debated for a long
      time. Some of these often forgotten developments are reviewed in support of the
      hypothesis, which allows a more comprehensive view of the complex in vivo
      situation at a time when in vitro models prevail.

PMID- 17453933
TI  - Critical observations on the neurotoxicity of silver.
AB  - Silver is a xenobiotic element with no recognized trace metal value in the human
      body. It is absorbed into the body through the lungs, gastrointestinal tract,
      mucus membranes of the urinogenital tract, and through the skin, mainly in the
      form of silver protein complexes. Although silver is metabolized throughout the
      soft tissues, available evidence from experimental animal studies and human
      clinical reports has failed to unequivocally establish that it enters tissues of
      the central nervous system or is a cause of neurotoxic damage. Argyria
      characterized by deposition of particles of silver sulfide or silver selenide is
      the principle contraindication for using silver in medical devices or
      occupationally. This presents discoloration of the skin but is not regarded as a
      health risk or manifestation of toxicity. No evidence is available to demonstrate
      the toxic risk of silver to the peripheral nervous system, although silver
      sulfide deposits have been identified in the region of cutaneous nerves.
      Transitory silver sulfide deposits seen in the tissues of the blood-brain and
      blood-CSF barriers are mostly lysosomally bound or deposited on basement
      membranes or collagen without toxic effect. Silver is mostly excreted from the
      body in the urine and feces. Further research is indicated to evaluate the role
      of metal binding proteins including metallothioneins as cytoprotectants for
      neurological tissue.

PMID- 17453934
TI  - Grey goo on the skin? Nanotechnology, cosmetic and sunscreen safety.
AB  - Many modern cosmetic or sunscreen products contain nano-sized components.
      Nanoemulsions are transparent and have unique tactile and texture properties;
      nanocapsule, nanosome, noisome, or liposome formulations contain small vesicles
      (range: 50 to 5000 nm) consisting of traditional cosmetic materials that protect
      light-or oxygen-sensitive cosmetic ingredients. Transdermal delivery and cosmetic
      research suggests that vesicle materials may penetrate the stratum corneum (SC)
      of the human skin, but not into living skin. Depending on the physical/chemical
      properties of the ingredient and the formulation, nano-sized formulations may
      enhance or reduce skin penetration, albeit at a limited rate. Modern sunscreens
      contain insoluble titanium dioxide (TiO(2)) or zinc oxide (ZnO) nanoparticles
      (NP), which are colorless and reflect/scatter ultraviolet (UV) more efficiently
      than larger particles. Most available theoretical and experimental evidence
      suggests that insoluble NP do not penetrate into or through normal as well as
      compromised human skin. Oral and topical toxicity data suggest that TiO(2) and
      ZnO NP have low systemic toxicity and are well tolerated on the skin. In vitro
      cytotoxicity, genotoxicity, and photogenotoxicity studies on TiO(2) or other
      insoluble NP reporting uptake by cells, oxidative cell damage, or genotoxicity
      should be interpreted with caution, since such toxicities may be secondary to
      phagocytosis of mammalian cells exposed to high concentrations of insoluble
      particles. Caution needs to be exercised concerning topical exposure to other NP
      that either have characteristics enabling some skin penetration and/or have
      inherently toxic constituents. Studies on wear debris particles from surgical
      implants and other toxicity studies on insoluble particles support the
      traditional toxicology view that the hazard of small particles is mainly defined
      by the intrinsic toxicity of particles, as distinct from their particle size.
      There is little evidence supporting the principle that smaller particles have
      greater effects on the skin or other tissues or produce novel toxicities relative
      to micro-sized materials. Overall, the current weight of evidence suggests that
      nano-materials such as nano-sized vesicles or TiO(2) and ZnO nanoparticles
      currently used in cosmetic preparations or sunscreens pose no risk to human skin
      or human health, although other NP may have properties that warrant safety
      evaluation on a case-by-case basis before human use.

PMID- 17453935
TI  - Guidelines for treating cardiac manifestations of organophosphates poisoning with
      special emphasis on long QT and Torsades De Pointes.
AB  - Organophosphate poisoning may precipitate complex ventricular arrhythmias, a
      frequently overlooked and potentially lethal aspect of this condition. Acute
      effects consist of electrocardiographic ST-T segment changes and AV conduction
      disturbances of varying degrees, while long-lasting cardiac changes include QT
      prolongation, polymorphic tachycardia ("Torsades de Pointes"), and sudden cardiac
      death. Cardiac monitoring of organophosphate intoxicated patients for relatively
      long periods after the poisoning and early aggressive treatment of arrhythmias
      may be the clue to better survival. We present here a review of the literature
      with a focus on late cardiac arrhythmias (mainly "Torsades de pointes"), possible
      mechanisms, and treatment modalities, with special emphasis on postpoisoning
      monitoring for development of arrhythmias.

PMID- 17453936
TI  - Ethyl tertiary-butyl ether: a toxicological review.
AB  - A number of oxygenated compounds (oxygenates) are available for use in gasoline
      to reduce vehicle exhaust emissions, reduce the aromatic compound content, and
      avoid the use of organo-lead compounds, while maintaining high octane numbers.
      Ethyl tertiary-butyl ether (ETBE) is one such compound. The current use of ETBE
      in gasoline or petrol is modest but increasing, with consequently similar trends
      in the potential for human exposure. Inhalation is the most likely mode of
      exposure, with about 30% of inhaled ETBE being retained by the lungs and
      distributed around the body. Following cessation of exposure, the blood
      concentration of ETBE falls rapidly, largely as a result of its metabolism to
      tertiary-butyl alcohol (TBA) and acetaldehyde. TBA may be further metabolized,
      first to 2-methyl-1,2-propanediol and then to 2-hydroxyisobutyrate, the two
      dominant metabolites found in urine of volunteers and rats. The rapid oxidation
      of acetaldehyde suggests that its blood concentration is unlikely to rise above
      normal as a result of human exposure to sources of ETBE. Single-dose toxicity
      tests show that ETBE has low toxicity and is essentially nonirritant to eyes and
      skin; it did not cause sensitization in a maximization test in guinea pigs.
      Neurological effects have been observed only at very high exposure
      concentrations. There is evidence for an effect of ETBE on the kidney of rats.
      Increases in kidney weight were seen in both sexes, but protein droplet
      accumulation (with alpha(2u)-globulin involvement) and sustained increases in
      cell proliferation occurred only in males. In liver, centrilobular necrosis was
      induced in mice, but not rats, after exposure by inhalation, although this lesion
      was reported in some rats exposed to very high oral doses of ETBE. The proportion
      of liver cells engaged in S-phase DNA synthesis was increased in mice of both
      sexes exposed by inhalation. ETBE has no specific effects on reproduction,
      development, or genetic material. Carcinogenicity studies have been conducted
      with ETBE, TBA, and ethanol (included in this review as an endogenous precursor
      of acetaldehyde in the absence of TBA). A single experiment with ETBE in rats and
      several experiments with ethanol in rats and mice were not considered adequate
      for an evaluation of ETBE carcinogenicity. In male rats only, TBA induced
      alpha(2u)-globulin nephropathy-related renal tubule adenomas. These are generally
      considered to have no human relevance. In addition, increases in thyroid
      follicular cell adenoma incidence were associated with TBA treatment in female
      mice. This result lacks independent confirmation and is not supported by
      experiments in which similar or higher internal doses of TBA were delivered.

PMID- 17453937
TI  - A review of the hepatotoxic plant Lantana camara.
AB  - Lantana (Lantana camara Linn) is a noxious weed that grows in many tropical and
      subtropical parts of the world. Ingestion of lantana foliage by grazing animals
      causes cholestasis and hepatotoxicity. Both ruminants and nonruminant animals
      such as guinea pigs, rabbits, and female rats are susceptible to the hepatotoxic
      action of lantana toxins. The hepatotoxins are pentacyclic triterpenoids called
      lantadenes. Molecular structure of lantadenes has been determined. Green unripe
      fruits of the plant are toxic to humans. Lantana spp. exert allelopathic action
      on the neighboring vegetation. The allelochemicals have been identified as
      phenolics, with umbelliferone, methylcoumarin, and salicylic acid being the most
      phytotoxic. In addition to phenolics, a recent report indicates lantadene A and B
      as more potent allelochemicals. Management of lantana toxicosis in animals is
      achieved by drenching with activated charcoal and supportive therapy. Recent
      reports on the bilirubin clearance effect of Chinese herbal tea Yin Zhi Huang
      (decoction of the plant Yin Chin, Artemisia capillaries, and three other herbs)
      or its active ingredient 6,7-dimethylesculetin, in jaundice are very exciting and
      warrant investigations on its, possible, ameliorative effects in lantana
      intoxicated animals. Research is being conducted on new drug discovery based on
      natural products in different parts of the lantana plant.

PMID- 17453939
TI  - Tear dynamics model.
AB  - PURPOSE: Quantitative understanding of tear dynamics may help in developing
      better ophthalmic drug delivery vehicles and dry eye treatments. This paper
      attempts to develop a comprehensive model that can predict the effect of
      physiological parameters on various issues related to tear dynamics. METHODS: The
      model is based on mass balances of water and solutes such as glucose, sodium,
      potassium, and chloride. The mass balances require models for the drainage of
      fluid through the canaliculi and the transport of tears and solutes through the
      conjunctiva. The model parameters are obtained by simulating Ussing-chamber
      experiments. The differential equations for the unsteady balances are solved
      numerically. RESULTS: The model predicts that under normal conditions, the tear
      volume, tear osmolarity and potential are 7.1 microl, 297.6 mM, and -15.1 mV,
      respectively. The model also predicts that the conjunctiva is secretory and
      contributes about 25% of the total tear production. We also predict the effect of
      evaporation on tear physiology and show that an increase in evaporation increases
      osmolarity, reduces tear volume, and increases conjuctival secretion.
      Additionally, the new tear dynamics model helps assess the effect of osmolarity
      of the instilled drops, insertion of punctum plugs and use of moisture chamber as
      treatments for dry eyes. Furthermore, the model is used to predict the effect of
      modulation of specific transport pathways, which is proposed as a potential
      remedy for dry eyes, on conjuctival secretion and total tear volume. CONCLUSIONS:
      Most of the predicted results agree with the reported experimental results, at
      least qualitatively. However, some predictions disagree with experiments
      suggesting that further improvements in the model are needed. The model developed
      in this paper can improve our understanding of tear dynamics and also serve as a
      tool to evaluate the efficacy of various modalities at treating dry eyes.

PMID- 17453940
TI  - Using basement membrane of human amniotic membrane as a cell carrier for
      cultivated cat corneal endothelial cell transplantation.
AB  - PURPOSE: To study the feasibility of using basement membrane of human amniotic
      membrane (BMHAM) as a carrier for transplantation of cultivated cat corneal
      endothelial cells (cCCECs). METHODS: BHMAM was obtained by enzymic digestion.
      cCCECs were seeded on the BMHAM and cultivated traditionally. The resulting
      continuous monolayer of cCCECs was transplanted onto the cat corneal graft
      stripped of the Descemet membrane with endothelium. To determine whether the
      transplanted cCCECs were vital and functional in vivo, the corneal grafts were
      examined by slit-lamp microscope every day for 6 weeks, and corneal thickness was
      measured by ultrasonic pachymetry. Either in vivo or in vitro, the cCCEC sheets
      on BMHAMs were examined morphologically by light and electron microscope, and the
      cell density was measured. RESULTS: Seven to 10 days after seeding on the BMHAM,
      the cCCECs were confluent and formed a continuous monolayer with 3486 +/- 53
      cells/mm(2) cell density. Like normal corneal endothelial cells, the cCCECs were
      almost hexagonal, squamous, and uniform in size. After transplantation, most
      cells were vital and functional nearly enough to maintain corneal graft thickness
      and transparency without rejection for at least 6 weeks. Six weeks after
      operation, the average thickness of the transplanted corneal grafts was only
      slightly greater than that before operation. Compared with that in vitro, after
      transplantation there was 5% to 8% reduction per week in cell density, which
      lasted for almost 3 weeks. After that, the average cCCEC density of corneal
      grafts was 2837 +/- 57 cells/mm(2) and quite stable maintained. CONCLUSIONS: This
      study demonstrated that BMHAM would be an ideal alternative for corneal Descemet
      membrane and a cell carrier for cCCEC transplantation.

PMID- 17453941
TI  - The effects of systemic alpha-1 adrenergic antagonists on pupil diameter in rats.
AB  - PURPOSE: To investigate the effects of alpha-1 adrenergic blockers on pupil
      diameter (PD) in rats. METHODS: Four groups, with 10 rats each, were designed to
      receive terazosin, tamsulosin, doxazosin, and no medication. Dilated pupil
      diameter (PD) measurements were performed 24 hr before, 24 hr after, and 30 days
      after the initiation of medication, and after 30 days of washout. The intergroup
      and intragroup differences in PD were evaluated using one-way ANOVA and Wilcoxon
      signed rank test, respectively. RESULTS: In day 1, PD decreased in both eyes
      significantly only in tamsulosin and doxazosin groups, but these effects became
      insignificant at 30 days of treatment (p > 0.05). The control group showed no
      significant difference in PD (p > 0.05). PD values returned to baseline after the
      washout period in all groups. CONCLUSIONS: A significant reduction in PD occurred
      in two of the three groups with alpha-1 adrenergic blockers (tamsulosin and
      doxazosin), but this effect was not sustained at 30 days. Further functional and
      structural studies of the iris are needed to determine the clinical significance
      of these findings.

PMID- 17453942
TI  - Regulation of gap junction intercellular communication in primary canine lens
      epithelial cells: role of protein kinase C.
AB  - PURPOSE: Gap junction intercellular communication (GJIC) is important in
      maintaining lens epithelial cell homeostasis and reductions in GJIC may be
      associated with the development of cataract. Protein kinase C (PKC) activation
      can disrupt gap junction communication via phosphorylation of connexin 43 (C x
      43) proteins that compose gap junction channels. This study examined the role of
      PKC activation in modulating GJIC in a primary canine lens epithelial cell (LEC)
      line. METHODS: TPA (12-O-tetradecanoyl-phorbol-acetate), a potent PKC activator
      and inhibitor of GJIC, was utilized in the present study. Primary cultures of
      canine LEC were treated with TPA (0-1000 ng/ml) for 0.5 hr and GJIC was assessed
      by scrape loading/dye transfer (SL/DT), and immunoblotting to detect
      phosphorylation of C x 43 protein. Inhibition of general and calcium-dependent
      PKC activity was achieved by pretreatment of cells with GF109203X and Go6976,
      respectively. RESULTS: Treatment with TPA (1-1000 ng/ml) significantly decreased
      GJIC in canine LEC as assessed by SL/DT. Pretreatment with 10 and 100 ng/ml TPA
      decreased GJIC by 80% as compared to controls and increased Cx43 phosphorylation
      as assessed by immunoblotting. Pretreatment of cells with GF109203X and Go6976,
      partially restored TPA-inhibited GJIC by 40% and 60%, respectively, and reduced C
      x 43 phosphorylation. Expression of calcium dependent PKC isoforms was detected
      in canine whole lens and LEC. CONCLUSIONS: Treatment with TPA significantly
      reduces GJIC in canine LEC. These effects are mediated, in part, by activation of
      calcium-dependent PKC isoforms. Primary canine LEC are a useful model in the
      study of the molecular mechanisms involved in GJIC and cataractogenesis.

PMID- 17453943
TI  - Role of extracellular signal-regulated kinase in glutamate-stimulated apoptosis
      of rat retinal ganglion cells.
AB  - PURPOSE: To investigate the involvement of the extracellular signal-regulated
      kinase (ERK) signaling pathway after intravitrevous injection of glutamate in rat
      retina. METHODS: Three groups of five Sprague-Dawley rats each were studied.
      Group I was a normal control group, intravitreal saline injections. In Group II,
      one eye received an intravitreal glutamate injection (375 nmol, dissolved in
      saline) while the contralateral eye served as control. In Group III, intravitreal
      PD98059 (100 micro mol, an inhibitor of ERK) injections were administered 1 hr
      before glutamate injections. Seven days after injections, phosphorylated
      (activated) ERK in retina was localized by immunohistochemistry and fluorescent
      double labeling of retinal cryosections. Specific ERK blockade was documented to
      assess the functional significance of activated ERK. TUNEL staining was performed
      to assess apoptotic cell death. RESULTS: Expression of phosphorylated ERK in rat
      retina was observed in the inner nuclear layer, the outer nuclear layer, and the
      nerve fiber layer after 3 days intravitreous injection of glutamate, increasing
      significantly after 7 days. Double immunofluorescence labling demonstrated that
      the increased retinal immunostaining for phospho-ERK was predominantly localized
      to the retinal Muller cells after 7 days intravitreous injection of glutamate.
      Moreover, blocking activation of ERK significantly improved the number of TUNEL
      positive cells in the eyes receiving intravitreal PD98059 injections compared
      with the eyes receiving glutamate injections. CONCLUSIONS: The ERK pathway is
      involved in signal transduction in the retina after excessive stimulation by
      glutamate, which may contribute to the antiapoptotic role in retinal ganglion
      cell death induced by glutamate.

PMID- 17453944
TI  - Evaluation of macular changes after uncomplicated phacoemulsification surgery by
      optical coherence tomography.
AB  - PURPOSE: To evaluate the effect of uncomplicated phacoemulsification surgery on
      macula by optical coherence tomography (OCT). METHODS: A total of 110 eyes of 102
      patients who underwent uncomplicated phacoemulsification and foldable intraocular
      lens implantation at Beyoglu Eye Research and Training Hospital between February
      and March 2005 and who were without any systemic disease, fundus or other ocular
      pathology were included. Postoperatively, topical prednisolone acetate (6 x 1)
      and ofloxacine (5 x 1) was started, and by decreasing the dosage progressively,
      treatment was continued for 6 weeks. Full ophthalmologic and OCT examinations
      were done preoperatively and at the postoperative 1st day, 1st week, 1st, 3rd,
      and 6th months. Mean retinal thicknesses, volumetric analyses at central fovea,
      superior, inferior, temporal, and nasal macular quadrants, and thinnest foveal
      retinal thicknesses were recorded. Preoperative and postoperative measurements
      were analyzed statistically by using ANOVA test, paired samples t-test with
      Bonferroni correction, and Pearson's correlation test. RESULTS: The mean central
      foveal retinal thickness was preoperatively 202.4 +/- 25.9 micro m,
      postoperatively 200.4 +/- 26.1 micro m at 1st day (p = 0.29), 208.4 +/- 27.6
      micro m at 1st week (p = 0.29), 226.2 +/- 54.9 micro m at 1st month, 215.2 +/-
      24.0 micro m at 3rd month, 213.5 +/- 29.4 micro m at 6th month (p < 0.001).
      Perifoveal macular thicknesses at superior, inferior, temporal, and nasal
      quadrants were 264.9 +/- 28.8 micro m, 266.1 +/- 29.5 micro m, 255.0 +/- 31.3
      micro m, 260.3 +/- 34.0 micro m, respectively, preoperatively; 287.9 +/- 28.4
      micro m, 288.0 +/- 26.3 micro m, 286.8 +/- 33.1 micro m, 272.0 +/- 32.4 micro m,
      respectively, at postoperative 1st month (p < 0.001). The change in mean central
      foveal thickness, foveal thinnest retinal thickness, mean perifoveal retinal
      thickness and volumetric analyses was insignificant at postoperative 1st day (p >
      0.05), and significant at 1st week, 1st, 3rd, and 6th months (p < 0.05 for all
      measurements). CONCLUSIONS: Statistically significant increase in macular
      thickness was detected at postoperative early periods, after the 1st week after
      uncomplicated cataract operation. The increase in macular thickness starts from
      parafoveal regions. Longer follow-up of patients is required for the macular
      consequences, and different treatment protocols should be studied in a randomized
      controlled fashion.

PMID- 17453945
TI  - Expression of adenylate kinase 1 in bovine retinal cytosol.
AB  - Adenylate kinases (AKs) are ubiquitous phosphotransferases that contribute to
      homeostasis of adenine nucleotide composition in cells. Six AK isoforms were
      found in vertebrates. We report that soluble AK isoform 1 is expressed in the
      cytosol of bovine retina consistently devoid of rod outer segments.
      Immunoblotting analysis with a polyclonal antibody raised against soluble
      adenylate kinase and subsequent sequencing of eluted peptide by matrix-assisted
      laser desorption/ionization-time-of-flight mass spectrometry allowed enzyme
      isolation by joining purification methods to two-dimensional electrophoresis. In
      this study, we found that cytosolic adenylate kinase isoform 1 is expressed in
      bovine retina. Cytoplasmic AK1 would physiologically contribute to retinal energy
      metabolism.

PMID- 17453946
TI  - Sustained elevation of intracellular cGMP causes oxidative stress triggering
      calpain-mediated apoptosis in photoreceptor degeneration.
AB  - Sustained elevation in cGMP and a concomitant increase in intracellular Ca(2+)
      levels in the rd1 photoreceptors are followed by a rapid loss of photoreceptors.
      In a murine-derived photoreceptor cell line, 661W, treated with the
      phosphodiesterase inhibitor IBMX or the cyclic GMP-gated channel agonist 8-bromo
      cGMP, it was previously found that the induced cell death was mediated by calpain
      and caspase-3. Because oxidative stress is a common product of ionic imbalance or
      elevated Ca(2+), we tested the role of oxidative stress in cGMP-induced
      photoreceptor cell death. In the rd1 mouse retina, oxidative stress was found to
      precede calpain and caspase-3 activation. In 661W cells, the increase in
      intracellular cGMP and Ca(2+) resulted in the generation of reactive oxygen
      species (ROS), the activation of oxidative stress enzymes, and the activation of
      calpain, followed by apoptosis mediated by the effector caspase-3. All these
      events, including calpain activation, were ameliorated by docosahexanoic acid
      (DHA). The cell-permeable inhibitor of calpain, SJA6017, while inhibiting cell
      death, had no effect on the generation of oxidative stress. These results
      establish a central role for oxidative stress in cGMP-induced cell death and
      suggest a ROS-mediated sequential activation of signal transduction events, which
      provide targets for future treatment strategies.

PMID- 17453947
TI  - Oxysterols induced inflammation and oxidation in primary porcine retinal pigment
      epithelial cells.
AB  - PURPOSE: Aging is associated with an accumulation of cholesterol esters in the
      Bruch membrane. Cholesterol esters are prone to undergo oxidation and generate
      oxysterols that have cytotoxic and proinflammatory properties. We investigated
      the effects of three oxysterols on mitochondrial dysfunctions, inflammation, and
      oxidative stress in primary cultures of porcine retinal pigment epithelial (RPE)
      cells. METHODS: RPE cells were incubated with oxysterols (50 micro M of 24
      hydroxycholesterol, 25-hydroxycholesterol, or 7-ketocholesterol) for 24 hr and 48
      hr. Oxysterol content was determined in cells and in corresponding media by gas
      chromatography. Mitochondrial activity was measured by mitochondrial
      dehydrogenase activity. The intracellular formation of reactive oxygen species in
      RPE cells was detected by using the fluorescent probe DCFH-DA. IL-8 was assayed
      in the supernatants by ELISA, and the corresponding cellular transcripts were
      semiquantified by RT-PCR. RESULTS: Analyses of the oxysterols content in the RPE
      cells and corresponding media suggested a high rate of cellular uptake, although
      some differences were observed between 7-ketocholesterol on the one hand and 24
      hydroxycholesterol and 25-hydroxycholesterol on the other hand. All oxysterols
      induced slight mitochondrial dysfunctions but a significant 2- to 4-fold increase
      in reactive oxygen species (ROS) production compared with the control. They also
      enhanced IL-8 gene expression and IL-8 protein secretion in the following
      decreasing order: 25-hydroxycholesterol > 24-hydroxycholesterol > 7
      ketocholesterol. CONCLUSIONS: We conclude that in confluent primary porcine RPE
      cells, 24-hydroxycholesterol, 25-hydroxycholesterol, and 7-ketocholesterol are
      potent inducers of oxidation and inflammation.

PMID- 17453948
TI  - Expression of epidermal growth factor receptor, ezrin, hepatocyte growth factor,
      and c-Met in uveal melanoma: an immunohistochemical study.
AB  - The immunoreactivity of epidermal growth factor receptor (EGFR) ezrin, hepatocyte
      growth factor receptor (HGF), and c-Met was studied in 60 uveal melanomas and was
      correlated with clinicopathologic parameters. Metastases were diagnosed in the
      patients with uveal melanoma between 5 years and 8 years (median, 6.5 years)
      after enucleation. Using Kaplan-Meier statistical analysis, we found a
      significant association between high c-Met expression and death due to uveal
      melanoma (p < 0.03). EGFR was expressed in 18 of 60 (30%) tumors; ezrin was
      expressed in 30 of 60 (50%) tumors. Tumors with liver metastasis (n = 6) showed
      higher expression of c-Met (p = 0.0009) compared with the tumors with no
      extension/extrascleral extension without liver metastasis (groups A-45 and B-9).
      HGF was negative in all the six tumors that had liver metastasis. Further studies
      are required to understand the possible mechanism of ligand-independent c-Met
      activation in patients with uveal melanoma.

PMID- 17453949
TI  - The effect of methylprednisolone pulse treatment on cytokine network in Graves
      ophthalmopathy.
AB  - The etiology of Graves ophthalmopathy (GO), representing the most common
      extrathyroidal manifestation of Graves disease, is multifactorial. Among multiple
      genetic, environmental, and endogenous factors, cytokines play a critical role in
      its etiopathogenesis. We studied an effect of glucocorticoid therapy on the serum
      IL-6, IL-4, and IL-13 levels in 18 GO patients. All the patients presented
      euthyroid GO with over 4 points according to the CAS classification (range 4-6;
      mean 4.94). The patients were treated with methylprednisolone (1 g every second
      day for three times) followed by 6 months oral prednisone (60 mg/day, with
      gradual reduction). The clinical examination (Clinical Activity Score and the GO
      severity by modified NOSPECS classification) and measurement of anti-TPO, anti
      TG, anti-TSHR (TRAK), IL-6, IL-4, as well as IL-13 serum levels were performed
      before, after 2 weeks, and after 6 months of the glucocorticoid therapy.
      Significant serum IL-6 increases (p < 0.001) and moderate serum IL-4 and IL-13
      increases (p < 0.05) were found in GO patients compared with healthy controls.
      After 2 weeks of the therapy, the serum IL-6 levels decreased in majority of the
      patients, however after 6-month observation, lower serum IL-6 levels were only in
      8 patients who seemed to respond clinically to the therapy (mean value of the
      Clinical Activity Score decreased from 4.5 before the therapy initiation to 1.25
      after 6 months of the glucocorticoid therapy). No changes in IL-4 and IL-13 serum
      levels during the therapy were observed. Statistical analysis revealed a good
      correlation between serum IL-6 level and the Clinical Activity Score (p < 0.01).
      Based on the obtained data, we conclude that IL-6 plays an important role in GO.
      It seems that IL-6 may serve as a useful factor in the inflammatory events of GO.

PMID- 17453951
TI  - Evaluation of ocular surface changes in a rabbit dry eye model using a modified
      impression cytology technique.
AB  - PURPOSE: To evaluate the ocular surface changes in a rabbit dry eye model by
      using a modified impression cytology technique. METHODS: Nitrocellulose filter
      paper with a pore diameter of 0.45 microm was used to collect the specimens from
      12 rabbits that were injected with atropine every day for 3 days. Filter papers
      were kept in distilled water overnight and then dried to increase cell pickup.
      Samples were stained with periodic acid-Schiff. The mean temporal and superior
      bulbar conjunctival goblet cell densities were counted. The data were compared
      with transmission (ocular surface) and scanning electron microscopic (filter
      paper) examination of the ocular surface. RESULTS: In the acute stage of atropine
      injection, there was not a major change in the goblet cell count. Although the
      goblet cell distribution was variable over the ocular surface, the average cell
      density was 55.4+/-22 in the superior quadrant and 69.2+/-9 in the temporal
      quadrant. In the 3-day atropine-injection group, there was a marked decrease in
      goblet cells, and there was mucin accumulation rather than accumulation of the
      goblet cells. No morphologic differences could be observed with scanning electron
      microscopy between the regular nitrocellulose filter paper and the paper kept in
      distilled water. CONCLUSIONS: The findings indicate that keeping the filter paper
      in distilled water and then drying it improves cell pickup and ocular surface
      evaluation in rabbits.

PMID- 17453952
TI  - Effects of subretinal injection of patent blue and trypan blue in rabbits.
AB  - PURPOSE: To investigate the histologic and clinical effects of subretinal
      injection of patent blue (PB) and trypan blue (TB) in rabbits. METHODS: Dutch
      belted rabbits (n=8) were vitrectomized followed by subretinal injection of 2.4
      mg/ml PB (285 mOsm) and 1.5 mg/ml TB (312 mOsm); balanced salt solution (BSS)
      (300 mOsm) served as the control. Animals were examined 6, 12, and 24 hr and 14
      days after the procedure by fluorescein angiography (FA) and indirect
      ophthalmoscopy; for retinal toxicity, histologic evaluation studies were
      performed by light and transmission electron microscopy. RESULTS: FA examination
      demonstrated window defects suggestive of retinal pigment epithelium (RPE)
      atrophy in positions of subretinal TB injection, but this was not observed after
      subretinal injection of PB or BSS. Histologic evaluation disclosed only minimal
      abnormalities on the photoreceptor outer segment (POS) after subretinal injection
      of BSS during all follow-up. Subretinal injection of PB caused POS and
      photoreceptor inner segment (PIS) abnormalities 12 and 24 hr after surgery as
      well as outer nuclear layer (ONL) damage 14 days after surgery. Subretinal TB
      injection resulted in POS and PIS damage at 12 hr follow-up. The ONL damage was
      observed 24 hr after surgery; additionally, POS, PIS, ONL, and RPE abnormalities
      were observed 14 days after surgery after TB injection. CONCLUSIONS: Subretinal
      injection of TB induced more significant clinical and histologic damage of
      neurosensory retina/RPE than did PB or BSS. Future human studies are necessary to
      access the clinical relevance of these in vivo experiments.

PMID- 17453953
TI  - Feasibility of two-dimensional gel electrophoresis used for proteomic analysis of
      human scleral fibroblasts.
AB  - PURPOSE: This study used two-dimensional gel electrophoresis (2-DE) to analyze
      protein profiles for normal human scleral fibroblasts in order to provide a
      baseline for future study of proteomics of the sclera in experimental conditions.
      In addition, differences in the presence and amount of proteins from fibroblasts
      isolated from the anterior or posterior sclera were analyzed. METHODS: The
      fibroblasts from anterior and posterior sclera of two healthy donors were
      cultured separately. Proteins were extracted from the cell lines, run on 2-DE,
      and stained by Commassie blue R-250. The gel images were analyzed to detect
      differences in expression levels (at least a fivefold difference in intensity)
      and location of the protein spots between the anterior and posterior sclera.
      These protein spots were trimmed from the gels, digested with trypsin, identified
      by MALDI mass spectrometry, and functionally categorized with human cDNA and
      protein databases from NCBI. RESULTS: The number of spots detected was 455 and
      453 protein spots from the anterior and posterior scleral fibroblasts,
      respectively. The patterns of gel maps were very similar between the anterior and
      posterior sclera in each donor and between the donors in either the anterior or
      posterior sclera. Nine proteins showed a stronger expression in the anterior
      sclera compared with the posterior sclera. These proteins together with the two
      proteins that appeared only in the anterior sclera were mainly associated with
      anabolic metabolism in cells. Eight proteins showed a stronger expression in the
      posterior sclera, and seven of them were mainly associated with catabolic
      metabolism in cells. Among all 19 protein spots identified as being
      differentially expressed between fibroblasts originally isolated from the
      anterior or posterior sclera, 14 proteins had a pI (3.86-7.95) and molecular
      weight (23-66 kDa) consistent with those found in human from the database of NCBI
      and from SwissProt Entry Name. CONCLUSIONS: The distribution and levels of
      expression in proteins are very similar for both the anterior and posterior
      sclera in vitro, with only approximately 4% of the proteins demonstrating a
      differential level of expression (at least fivefold) between the two segments of
      the sclera.

PMID- 17453954
TI  - Assessment of automated screening for treatment-requiring diabetic retinopathy.
AB  - PURPOSE: To evaluate fundus photographic image analysis combining automated
      detection of red lesions, bright lesions, and image quality as a means of
      identifying treatment-requiring diabetic retinopathy in a screening population of
      diabetic patients. METHODS: This was a retrospective cross-sectional study of 106
      patients from a diabetic retinopathy screening clinic referred for
      photocoagulation treatment in the period from January 1996 to May 2002 on the
      basis of mydriatic 60-degree 35-mm color transparency fundus photography. One
      fovea-centered fundus photograph and one centered nasal of the optic disk from
      each of a subject's two eyes was selected for digitization and analyzed using a
      previously tested computerized red-lesion detection algorithm in combination with
      a new algorithm for detection of bright lesions and image quality. The algorithm
      was calibrated on an independent set of fundus photographs. RESULTS: Automated
      red-lesion detection identified 104 of 106 patients requiring photocoagulation
      treatment, whereas bright-lesion detection identified only 91 of the 106
      patients. Two patients who were not identified by either lesion detection
      algorithm were automatically detected as having poor image quality in one or both
      eyes. In the study sample, the risk of missing treatment-requiring retinopathy
      patients from being detected was 0.0% (estimated CI(95) 0.0-3.4%). CONCLUSIONS:
      The combination of automated detection of red lesions and poor image quality
      identified all treatment-requiring diabetic retinopathy patients in the study
      sample. No additional information was contributed by the automated bright-lesion
      detection.

PMID- 17453955
TI  - Effects of intravitreal moxifloxacin and dexamethasone in experimental
      Staphylococcus aureus endophthalmitis.
AB  - PURPOSE: To evaluate the effects of intravitreal moxifloxacin and moxifloxacin
      and dexamethasone combination in an experimental rabbit model of Staphylococcus
      aureus endophthalmitis. METHODS: The right eyes of 24 rabbits weighing 2 to 3 kg
      were used. Ten thousand colony-forming units (CFU) of S. aureus in 0.1 ml saline
      solution were inoculated into the vitreous cavity. The eyes were randomly
      assigned to one of the four groups equally. Twenty-four hours after the
      inoculation of S. aureus, group 1 received 50 microg moxifloxacin, group 2
      received 50 microg moxifloxacin plus 400 microg dexamethasone, and group 3
      received 1 mg vancomycin intravitreally. No treatment was given to group 4.
      Clinical examination scores were recorded. Vitreous aspirates were obtained for
      microbiological analysis just before sacrifice, and the eyes were enucleated for
      histopathologic examination. Statistical analysis was performed using Kruskal
      Wallis and Mann-Whitney U tests. RESULTS: In all treatment groups, mean number of
      CFU and histopathologic score were significantly lower compared with control
      group (p<0.05), and the difference between treatment groups was not statistically
      significant (p>0.05). The clinical score was not significantly different between
      groups (p>0.05). CONCLUSIONS: Intravitreal injection of 50 microg moxifloxacin
      was effective in the treatment of S. aureus endophthalmitis. Bacteriological,
      histopathologic, and clinical outcomes after treatment using moxifloxacin,
      moxifloxacin and dexamethasone combination, and vancomycin were comparable.
      Intravitreal moxifloxacin may be an option in the treatment of S. aureus
      endophthalmitis.

PMID- 17453956
TI  - Multifocal electroretinography, color discrimination and ocular toxicity in
      tamoxifen use.
AB  - PURPOSE: To study prospectively retinal function, color discrimination, and
      ocular toxicity in women treated with standard-dosage tamoxifen for breast
      cancer. METHODS: Thirty visually asymptomatic patients with at least 2 years of
      continuous tamoxifen therapy underwent multifocal electroretinography (ERG),
      color discrimination testing, and ophthalmic examination. The results were
      compared with 17 patients who were not taking tamoxifen after breast cancer
      surgery and to an additional age-matched group of 21 healthy women. RESULTS:
      Multifocal electroretinogram amplitudes and latencies were comparable among the
      three studied groups, and individual recordings were within age norms from our
      own lab. In the treated group, mild diffuse color vision loss was found in two
      patients with normal fundi. Three other patients had ocular toxic effects, with
      two cases of refractile retinal crystals and one case of keratopathy.
      CONCLUSIONS: The aspects of central retinal function that are assessed by
      multifocal ERG were not affected even after at least 2 years of tamoxifen use,
      suggesting that the multifocal ERG is not sufficiently sensitive to detect
      tamoxifen-associated change that might occur. Some degree of color vision loss
      and ocular toxic effects were found in a few cases of this cohort suggesting that
      women using tamoxifen should receive an eye exam at least as often as recommended
      for middle-aged people.

PMID- 17453957
TI  - ATP-induced relaxation of porcine retinal arterioles depends on the perivascular
      retinal tissue and acts via an adenosine receptor.
AB  - PURPOSE: Purinergic compounds and cyclooxygenase inhibitors are involved in the
      tone regulation of isolated retinal arterioles in vitro, but it is unknown
      whether the perivascular retinal tissue influences these effects. METHODS:
      Adenosine-and ATP-induced vasodilation of porcine retinal arterioles was studied
      in a wire myograph before and after removal of the perivascular tissue. RESULTS:
      Both adenosine and ATP caused relaxation of the studied arterioles. This effect
      depended on the perivascular tissue and could be blocked by antagonists but was
      unaffected by ibuprofen. CONCLUSIONS: The relaxation of porcine retinal
      arterioles induced by purinergic compounds is modulated by the perivascular
      retinal tissue.

PMID- 17453958
TI  - Cholesterol-24S-hydroxylase (CYP46A1) is specifically expressed in neurons of the
      neural retina.
AB  - Increasing biological findings argue for the importance of cholesterol-24S
      hydroxylase (CYP46A1) in cholesterol homeostasis in cerebral structures. Based on
      the similarity between the brain and the neural retina, the aim of the current
      study was to evaluate the expression of CYP46A1 in the mammalian retina. RT-PCR
      analysis of CYP46A1 in bovine samples revealed the highest expression in the
      neural retina. The retinal pigment epithelium expressed CYP46A1 gene at a low
      level while the ciliary body showed no expression. Immunohistochemical evaluation
      of the posterior pole of rat retina showed that the protein is specifically
      expressed in neurons, whereas cone-rods photoreceptors were negative for CYP46A1
      staining. The metabolite produced by CYP46A1, 24S-hydroxycholesterol, was almost
      exclusively found in neural retina, the concentration therein being more than 10
      fold higher than in the retinal pigment epithelium or the ciliary body. The
      results of the current study are consistent with our primary hypothesis: the
      neural retina specifically expresses cholesterol-24S-hydroxylase, a metabolizing
      enzyme responsible for the removal of cholesterol in neurons. Based on the link
      between cholesterol-24S-hydroxylase, 24S-hydroxycholesterol, and neurologic
      disorders, CYP46A1 may be a valuable gene candidate for retinal pathologies like
      age-related macular degeneration or glaucomas, and 24S-hydroxycholesterol may be
      involved in the onset of the degenerative processes in these diseases.

PMID- 17453959
TI  - Expression of ubiquitin carboxy-terminal hydrolase-l1 in photocoagulated human
      retinal pigment epithelial cells.
AB  - PURPOSE: To date, the exact mechanisms involved in laser-induced remission of
      ocular neovascular disorders are still poorly understood. Recent studies suggest
      that the expression of various antiangiogenic cytokines is upregulated after
      thermal photocoagulation. In the current study, we sought to identify novel laser
      regulated proteins in cultured human retinal pigment epithelial (HRPE) cells.
      METHODS: Protein extracts from photocoagulated HRPE cells were subjected to 2D
      gel electrophoresis. Potentially regulated protein spots were identified by mass
      spectroscopy. Regulation of protein and mRNA was determined by Western blot
      analysis and reverse transcription-polymerase chain reaction, respectively.
      RESULTS: 2D-Gel electrophoresis of HRPE whole-cell extracts exposed to
      photocoagulation revealed a reproducible increase in a protein band identified as
      ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) compared with untreated
      controls. Protein levels showed a time-dependent upregulation over 24 hr. UCH-L1
      mRNA was maximally increased after 8 hr. CONCLUSIONS: Our findings indicate that
      the ubiquitin-proteasome system contributes to the effects seen clinically after
      thermal photocoagulation in eyes with neovascular diseases of the retina or
      choroid. Because ubiquitin carboxy-terminal hydrolase-L1 has been shown to be
      involved in the regulation of cell cycle proteins, it may be speculated that
      deubiquitinating enzymes have a role in the regeneration and proliferation of
      retinal pigment epithelial cells.

PMID- 17453960
TI  - Corneal virulence of Pseudomonas aeruginosa elastase B and alkaline protease
      produced by Pseudomonas putida.
AB  - PURPOSE: To measure the specific virulence contributions of two Pseudomonas
      aeruginosa proteases, elastase B and alkaline protease, when expressed separately
      by Pseudomonas putida in a rabbit model of bacterial keratitis. METHODS: P.
      putida KT2440 was transformed with plasmids that enabled the extracellular
      production of either elastase or alkaline protease. Protease expression was
      confirmed by zymography and immunoblotting. P. putida expressing elastase,
      alkaline protease, or vector alone was injected intrastromally (10(3) colony
      forming units [CFU]) into rabbit corneas (n=6). Infected eyes were graded by slit
      lamp examination (SLE) at 20, 24, 28, and 32 hr postinfection (PI). Rabbits were
      sacrificed at 33 hr PI, and the log CFU (+/-SEM) per cornea was determined.
      RESULTS: SLE scores for eyes infected with P. putida producing elastase were
      significantly higher than those infected with vector alone at all time points
      (p<or=0.008). SLE scores for eyes infected with P. putida producing alkaline
      protease were not significantly higher than the control (p>or=0.1), but small
      erosions formed in 33% of corneas. At both 24 and 28 hr PI, the SLE scores for
      corneas infected with P. putida producing elastase were significantly higher than
      those infected with P. putida producing alkaline protease (p<or=0.002).
      CONCLUSIONS: Elastase production by P. putida caused significant increases in SLE
      scores whereas expression of alkaline protease caused limited corneal erosions.
      This suggests that the production of elastase during P. aeruginosa keratitis
      enhances ocular pathology, whereas alkaline protease production contributes to
      limited corneal erosion.

PMID- 17453961
TI  - Lack of association between pseudoexfoliation syndrome and manganese superoxide
      dismutase polymorphism.
AB  - PURPOSE: The aim of this clinical study was to investigate the possible
      association between manganese superoxide dismutase (Mn-SOD) enzyme polymorphism
      in the mitochondrial targeting sequence and pseudoexfoliation syndrome. METHODS:
      Ala (GTT) or Val (GCT) polymorphism in the signal peptide of Mn-SOD gene was
      evaluated using a primer pair to amplify a 107-bp fragment followed by digestion
      with restriction enzyme NgoM IV. RESULTS: The frequencies of Ala-9 and Val-9
      variants and genotypes of Mn-SOD were similar in the controls and
      pseudoexfoliation syndrome patients. CONCLUSIONS: These results suggest no major
      modifying role for the Mn-SOD gene polymorphism in patients with
      pseudoexfoliation syndrome.

PMID- 17453962
TI  - Manipulating regulatory T cells.

PMID- 17453963
TI  - Immune reconstitution after unrelated cord blood transplantation.
AB  - Over the past years unrelated cord blood transplant (UCBT) has emerged as an
      effective alternative to unrelated donor blood and marrow transplantation.
      However, despite several advantages, its success is limited by the high incidence
      of opportunistic infections (OI), most of which are viral. Infection-related
      mortality is the primary cause of death after UCBT with most deaths occurring in
      the first 3-6 months post transplant. For several months, until recovery of the
      thymus is restored to support de novo T cell generation, protective antiviral
      immunity depends on the activity of post-thymic T cells infused within the cord
      blood (CB) grafts. However, almost all CB T cells are antigen inexperienced
      (naive) lymphocytes that have been functionally altered by placental factors to
      protect pregnancy. CB T cells need to undergo in vivo priming, Th1/Tc1
      maturation, and peripheral expansion before they can afford immunologic
      protection. This article provides an overview of what is currently known
      regarding the reconstitution of adaptive immunity following UCBT including our
      own data from prospective analyses of pediatric cohorts. Remarkable
      immunophenotypic changes are notable already in the first 2-3 weeks post-UCBT.
      These changes result from apparent 'homeostatic' peripheral T cell expansion in
      the lymphopenic environment. While we can identify patient- and graft-specific
      predictive factors, the concordant emergence of T cell subsets displaying the
      phenotype of Th1/Tc1 cytotoxic effector cells can be statistically linked to
      those UCBT recipients who will subsequently develop viral and other opportunistic
      infections. Antigen presenting dendritic cell reconstitution may also reflect
      alterations in immunocompetence due to OI and/or GVHD.

PMID- 17453964
TI  - CD69 expression as an index of T-cell function: assay standardization, validation
      and use in monitoring immune recovery.
AB  - BACKGROUND: CD69 is a surrogate marker of T-cell responsiveness to mitogen and Ag
      stimulus and can be used as a measure of T-lymphocyte activation. Quantitative
      flow cytometric determination of CD69 expression on T lymphocytes has several
      advantages over traditional lymphocyte proliferation assays, but this method has
      not yet been standardized for clinical applications. METHODS: We qualified a
      commercially available assay using the manufacturer's procedures for measurement
      of T-cell response to a mitogen (PHA), superantigen (Staphylococcus endotoxin B;
      SEB) and Ca(2+) ionophore (phorbyl myristate acetate; PMA) with peripheral blood
      from healthy volunteers. Following this, we tested the usefulness of the assay in
      determining T-cell responses to PHA and SEB for six immunocompromised patients.
      RESULTS: Healthy volunteers showed 17-fold increases in T-cell CD69 Ab bound per
      cell (ABC) with PHA stimulation compared with the baseline. SEB was also an
      effective T-cell activating agent, increasing CD69 ABC by 5-fold, comparable with
      results obtained with PMA stimulation. PHA- and SEB-stimulated T-cell CD69 ABC
      for patients 100 days post-BM transplant were generally below 1 SD of that from
      healthy volunteers. SEB-stimulated T-cell CD69 expression was significantly
      depressed for CD8(+) T cells while CD4(+) T-cell responses to SEB were generally
      within 1 SD of the mean for healthy volunteers. DISCUSSION: These results suggest
      that quantitative measurement of CD69 surface expression by flow cytometry is a
      useful diagnostic tool for detailed assessment of T-lymphocyte and subset
      activation.

PMID- 17453965
TI  - Rapid expansion of tumor-reactive cells from HLA-matched siblings for adoptive
      immunotherapy of melanoma.
AB  - BACKGROUND: Administration of expanded tumor-infiltrating lymphocytes in
      association with lymphodepleting chemotherapy is effective in some patients with
      advanced malignant melanoma. However, obtaining lymphocytes and subsequent
      expansion is labor intensive, making it impractical for broad clinical
      application. Allogeneic transplantation may have anti-melanoma efficacy because
      of a graft vs. tumor effect. The disappointing tumor control observed post
      transplant suggests that adoptive immunotherapy using melanoma-reactive cells
      will be essential for sustained responses. METHODS: Melanoma cell lines were
      grown from two patients with advanced disease. High-level CD80 and CD86
      expression was obtained in the tumor lines using a retroviral vector for gene
      transfer. Transduced melanoma and controls were cultured with mononuclear cells
      from HLA-identical sibling donors. RESULTS: Expression of CD80 and CD86,
      particularly the former, promoted marked expansion of lymphocytes from HLA
      matched sibling donors. Proliferation of up to 300-fold after 4 weeks of culture
      was observed. Lymphocytes from cultures stimulated with CD80 demonstrated
      cytotoxicity against recipient-untransfected melanoma (45-75% specific lysis at
      an E:T ratio of 50:1). Although expanded lymphocytes were predominantly CD4(+),
      cytotoxicity was greatest in the numerically smaller CD8(+) subpopulation. Both
      CD4(+) and CD8(+) cells secreted IFN-gamma (but not IL-4) on exposure to
      untransduced stimulator melanoma cells. DISCUSSION: Our strategy generates a
      large number of melanoma-reactive lymphocytes from HLA-identical siblings using a
      4-week culture strategy. Lymphocytes expanded in this way offer an alternative to
      tumor-infiltrating lymphocytes for allogeneic cellular immunotherapy after stem
      cell transplantation in young patients.

PMID- 17453966
TI  - Rapamycin enriches for CD4(+) CD25(+) CD27(+) Foxp3(+) regulatory T cells in ex
      vivo-expanded CD25-enriched products from healthy donors and patients with
      multiple sclerosis.
AB  - BACKGROUND: CD4(+) CD25(bright+) regulatory T cells (Treg) can be expanded to
      clinical doses using CD3/CD28 Ab-coated beads plus IL-2. However, this method
      requires high purity of the starting population to prevent overgrowth by non
      regulatory T cells. Rapamycin, an agent that inhibits T-cell proliferation but
      selectively spares Treg, may be a means to expand Treg from less pure CD25
      enriched cells. METHODS: CD25-enriched cells were prepared by a single-step
      immunomagnetic-selection using anti-CD25 microbeads. The cells were activated
      with a single addition of anti-CD3/CD28 beads and expanded in ex vivo 15-5% HS
      and autologous CD4(+) CD25(-) feeder cells,+/-rapamycin (0.01-20 ng/mL). IL-2 was
      added on day 3. Cells were rested for 2 days in ex vivo 15-5% HS and tested for
      phenotype, intracellular Foxp3 protein and suppressor activity. RESULTS: In the
      absence of rapamycin, CD25-enriched fractions expanded >17 000-fold by 21 days.
      Although suppressor activity was detected to day 14, it declined significantly by
      21 days as non-regulatory cells expanded. The addition of rapamycin inhibited
      expansion of non-regulatory T cells at doses > or =1 ng/mL while increasing
      suppressor activity and the percentage of CD4(+) CD25(+) CD27(+) Foxp3(+) cells.
      Rapamycin did not enrich for Foxp3(+) cells in expanded cultures of CD4(+) CD25(
      ) cells. Treg were also readily expanded in cultures of CD25-enriched cells
      obtained from patients with multiple sclerosis in the presence of rapamycin.
      DISCUSSION: The addition of 1-20 ng/mL rapamycin to CD25-enriched cultures
      increased the purity of cells with the phenotype and function of Treg. This
      approach may alleviate the need for rigorous enrichment of Treg prior to
      activation and expansion for potential clinical use.

PMID- 17453967
TI  - A randomized controlled clinical trial to determine the optimum duration of G-CSF
      priming prior to BM stem cell harvesting.
AB  - BACKGROUND: Harvesting of hemopoietic stem cells (HSC) from G-CSF-primed BM for
      autologous transplantation is an alternative to collection of unprimed BM or G
      CSF-primed peripheral blood (PB). However, the optimum number of days of G-CSF
      administration for this purpose is unknown. We set out to determine whether cell
      yields could be optimized by varying the number of days of G-CSF administration
      prior to BM stem cell harvesting. METHODS: We conducted a randomized controlled
      single-center trial of 6 days (the standard) vs. 4 days of G-CSF administration
      and compared yields of total nucleated cells (TNC), CD34(+) HSC and CFU-GM cells
      per kilogram patient body weight. Statistical analysis was by Student's t-test.
      RESULTS: Twenty-four patients were enrolled; 13 received 6 days and 11 received 4
      days of G-CSF administration. Analysis of the first harvest aspirate showed
      higher proportions of CD34(+) HSC (P=0.02) and CFU-GM (P=0.03) in the 4-day
      group. For the 6-day and 4-day groups, respectively, the median yield of TNC/kg
      was 6.5 x 10(8) and 5.4 x 10(8) (P=0.28), of CD34(+) cells/kg 0.56 x 10(6) and
      0.98 x 10(6) (P=0.04) and of CFU-GM cells/kg 1.66 x 10(5) and 1.55 x 10(5)
      (P=0.75). DISCUSSION: These results suggest that by 6 days the HSC-stimulating
      effect of G-CSF has passed its peak and that 4 days should be adopted as the
      standard for G-CSF priming prior to BM stem cell harvesting for autologous
      transplantation.

PMID- 17453968
TI  - Cord blood volume reduction using an automated system (Sepax) vs. a semi
      automated system (Optipress II) and a manual method (hydroxyethyl starch
      sedimentation) for routine cord blood banking: a comparative study.
AB  - Background With the development of cord blood banking, solutions have to be found
      to solve the storage space problem, by reducing the volume of cord blood units
      (CBU). Methods We compared total nucleated cell (TNC) and CD34(+) cell counts
      before and after processing with three different CBU volume reduction methods
      used consecutively in our bank: a manual method based on hydroxyethyl starch
      sedimentation (HES) (n=447), a top-and-bottom (TB) semi-automated method (n=181)
      using Optipress II, and the Sepax automated method (n=213). Statistical analysis
      was done using t-tests, linear regression and Spearman correlation coefficients.
      Adjusted variables included TNC, CD34(+) cell counts, CD34(+) cell percentage and
      CB volume before processing. Results TNC recovery was higher with Sepax (80.3+/
      7.7%) than with HES (76.8+/-9.1%) and TB (60.7+/-13.5%) (P<0.0001, both). It was
      higher with HES than with TB (P<0.0001). CD34(+) cell recovery was higher with
      Sepax (86+/-11.6%) than with HES (81.5+/-12.5%) and TB (82.0+/-17.7%) (P<0.008
      and <0.0001, respectively) and results with HES and TB were not significantly
      different (P=0.7). Interestingly, with Sepax, TNC and CD34(+) cell recoveries
      were not correlated with pre-processing values (P=0.8 and 0.4, respectively).
      Discussion In conclusion, the Sepax volume reduction method allows higher TNC and
      CD34(+) cell recoveries.

PMID- 17453969
TI  - Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro.
AB  - BACKGROUND: The multipotency of stromal cells has been studied extensively. It
      has been reported that mesenchymal stromal cells (MSC) are capable of
      differentiating into cells of multilineage. Different methods and reagents have
      been used to induce the differentiation of MSC. We investigated the efficacy of
      different growth factors in inducing MSC differentiation into neurons. METHODS:
      MSC from human BM were isolated and cultured in media supplemented with 10% FBS.
      These cells were identified and later induced to differentiate into neuron-like
      cells using different neurotrophic factors. Three different growth factors were
      used, either alone or in combination: brain-derived neurotrophic factor,
      epidermal growth factor and neural growth factor. RESULTS: After 10 days of
      culture, MSC showed neuron-like morphologic changes. Immunostaining showed that
      these cells expressed markers for neurons (growth-associated protein-43, neuron
      specific nuclear protein and neurofilament 200 kDa) and expression of these
      markers suggested the transition of immature stages to more mature stages of
      neuron-like cells. DISCUSSION: Our results show that BM-derived MSC can
      differentiate not only into target cells of mesodermal origin but also neuron
      like cells of ectodermal origin. The findings show that a combination of growth
      factors is more effective in inducing MSC into neuron-like cells.

PMID- 17453970
TI  - bFGF influences human articular chondrocyte differentiation.
AB  - BACKGROUND: The possible functional role of basic fibroblast growth factor (bFGF)
      in regulating the mitotic and metabolic activity of primary human articular
      chondrocytes was investigated. METHODS: [EF1]Chondrocytes were enzymatically
      isolated from femoral head cartilage, and were cultured in vitro in monolayer.
      bFGF-dependent cell proliferation, production of collagen type II and aggrecan
      were monitored 10 days after isolation. Furthermore, effect of bFGF on cell
      cycle, cell morphology, and mRNA expression of integrins and chondrogenic markers
      determined by real time PCR were analyzed. RESULTS: bFGF concentrations in
      supernatants of primary human articular chondrocytes peaked immediately after
      isolation and then declined. In a dose-dependent manner, bFGF enhanced cell
      amplification and viability. BFGF induced a decrease in the apoptotic cell
      population, while the number of proliferating cells remained unchanged.
      Supplementation of cell culture with bFGF reduced collagen type II mRNA by 49%,
      but increased expression of the integrin alpha(2) by 70%. bFGF did not
      significantly regulate the integrins alpha(1), alpha(5), alpha(10), alpha(v) and
      type I collagen. bFGF reduced the amount of collagen type II by 53%, which was
      correlated with diminished mRNA production. Monolayer cultured chondrocytes
      secreted significant amounts of aggrecan that decreased over time. Secretion of
      this cartilage-specific marker was further reduced by the addition of bFGF.
      DISCUSSION: These findings highlight the potential role of bFGF as an endogenous
      chondrocyte mediator that can enhance cell amplification and regulate cell
      differentiation.

PMID- 17453971
TI  - Primitive AML progenitors from most CD34(+) patients lack CD33 expression but
      progenitors from many CD34(-) AML patients express CD33.
AB  - BACKGROUND: AML blast populations are heterogeneous in their phenotype and
      functional properties, and contain a small subset of cells that regenerate
      leukemia in immunocompromised mice or produce clonogenic progeny in long-term
      cultures. This suggests the existence of a hierarchy of AML progenitor cells.
      CD33 is a myeloid marker absent on normal hematopoietic stem cells but expressed
      in about 75% of AML patients, and has been used for BM purging strategies and Ab
      targeted therapies. These CD33 Ab therapies benefit only a minority of AML
      patients, suggesting that AML stem cells are heterogeneous in their CD33
      expression. METHODS: In order to evaluate this question, we determined expression
      levels of CD34 and CD33 on AML progenitors with long-term in vitro proliferative
      ability and NOD/SCID engrafting ability. RESULTS: The CD34(+) CD33(-) subfraction
      contained the majority of progenitors detected in vitro and most often engrafted
      the mice. This proliferation was leukemic from the CD34(+) AML patients, however
      from the CD34(-) AML patients only normal progenitors were detected in this
      fraction in some cases. DISCUSSION: These data suggest that most leukemic
      progenitors of CD34(+) patients do not express CD33. In contrast, CD34(-) AML
      primitive leukemic progenitors may be CD33(+). CD34(-) AML patients could
      potentially benefit most from CD33-targeted therapies or purging.

PMID- 17453973
TI  - Describing participants in AAC research and their communicative environments:
      guidelines for research and practice.
AB  - PURPOSE: People who use augmentative and alternative communication (AAC) vary
      widely in their skills and communication needs. Interventions have been developed
      to meet different needs, but have met with varied success. Attempts to discover
      why interventions succeed or fail are hindered by the lack of detailed
      description of the research participants and the environments in which they
      communicate. This paper reviews the information commonly given about AAC research
      participants and presents guidelines for the description of people who use AAC,
      their conversation partners and their communicative environments. METHOD:
      Electronic databases were searched for AAC intervention research reports
      published between 1990 and 2004. Data on research participants and their
      communication environments were extracted from reviewed papers. Information given
      in published papers and variables known to affect communication were presented to
      an expert group. A modified Nominal Group technique was used to decide what
      information should be reported in AAC intervention research. RESULTS: Guidelines
      for participant description that link with the World Health Organization
      International Classification of Functioning, Disability and Health were developed
      from the results of the nominal group. CONCLUSIONS: Detailed information is
      needed to demonstrate efficacy of AAC interventions. Guidelines for participant
      description are presented and discussion of their utility is now needed.

PMID- 17453974
TI  - Lumbar spinal stenosis patients are satisfied with short-term results of surgery 
      younger age, symptom severity, disability and depression decrease satisfaction.
AB  - PURPOSE: To study the lumbar spinal stenosis (LSS) patients' (n = 98)
      satisfaction with surgery outcome and associated factors at three months post
      operative stage. METHOD: LSS-related physical functioning and pain were assessed
      with Oswestry disability index, Stucki questionnaire, Visual Analogue Scale and
      pain drawings. Depression was assessed with 21-item Beck Depression Inventory.
      Psychological well-being was assessed with the Life satisfaction scale, Toronto
      Alexithymia Scale and Sense of Coherence Scale. All questionnaires were
      administered before and 3 months after surgical treatment of LSS. Satisfaction
      with surgery outcome was assessed with a separate scale. RESULTS: Considerable
      improvement was evident in all the functional and pain-related variables. Two
      thirds (66%) of the patients were at least clearly satisfied with the surgery
      outcome. Younger age, symptom severity, disability and depression were
      independently associated with dissatisfaction with surgery outcome. CONCLUSION:
      The lack of physical, functional and emotional well-being is associated with the
      patients' dissatisfaction with the surgery outcome. Patient satisfaction is a
      valid outcome to be measured in LSS patients undergoing surgery. It is
      recommended that patients should be provided with realistic pre-operative patient
      information and that depression be assessed pre-operatively.

PMID- 17453976
TI  - Activities, participation and satisfaction one-year post stroke.
AB  - PURPOSE: To evaluate the chronic consequences of stroke in terms of activity
      limitations, restricted participation and dissatisfaction from life, and the
      relationship between these variables, in stroke survivors living in the community
      one-year post onset. METHOD: A total of 56 stroke patients (mean age: 57.7) who
      completed an in-patient rehabilitation programme, were evaluated one-year post
      onset in their homes, using the following instruments: Functional Independence
      Measure (FIM), Instrumental Activities of Daily Living Questionnaire (IADLq),
      Activity Card Sort (ACS), a work questionnaire, Life-Satisfaction Questionnaire
      (Li-Sat 9) and the Geriatric Depression Scale (GDS). RESULTS: One year post
      stroke onset the mean FIM motor score was 75.88 (max score: 91), yet more than
      50% of the sample still required assistance (usually mild to moderate) in
      dressing, bathing and use of stairs. The majority of the sample required full
      assistance in some IADL domains, notably meal preparation (77%), housekeeping
      (70%) and laundry (82%). Only one subject returned to paid employment and the
      mean activity level (ACS), representing the percentage of leisure and IADL
      activities retained from before stroke, was 42.8%. Satisfaction ratings were
      generally low but varied between domains. Only 39% were satisfied from 'life as a
      whole'. The lowest satisfaction rates were noted for 'vocational situation'
      (14%), 'leisure situation' (34%) and 'ability in self-care' (43%), whereas the
      satisfaction rate from family life was high (84%). Significant correlations were
      found between overall life satisfaction scores and the overall FIM motor, IADLq,
      and ACS scores (Pearson r values: 0.32, 0.48 and 0.57, respectively). Activity
      level was found to be a significant predictor of satisfaction (p = 0.007) beyond
      that accounted for by demographic variables and depression. CONCLUSIONS: Stroke
      survivors dwelling in the community demonstrate long-standing dissatisfaction one
      year post onset, correlating with activity limitation and restricted
      participation. The findings present a compelling need for rehabilitation services
      with a focus on participation in IADL and leisure activities, in order to improve
      the satisfaction of this population.

PMID- 17453975
TI  - Influence of the environment on activity performance in older women with heart
      failure.
AB  - PURPOSE: To examine the influence of the environment on activity performance in
      older women with heart failure living in the community. METHOD: The cross
      sectional study included 55 older women with heart failure. Differences in
      activity performance collected through performance observation in the clinic and
      home were analysed with repeated measures ANOVAs and paired samples t-tests.
      RESULTS: Overall, the influence of the environment in the clinic was neutral for
      activity independence, and disabling for activity safety and activity adequacy at
      the global level. At the domain level, functional mobility and personal care were
      more independent but equally safe and adequate in the clinic compared to the
      home, cognitively-oriented instrumental activities were less independent, safe
      and adequate in the clinic compared to the home, and physically-oriented
      instrumental activities were equally independent, but less safe and adequate in
      the clinic compared to the home. At the activity level, 6 activities were
      positively influenced by the environment in the clinic and 13 activities were
      negatively influenced. CONCLUSIONS: Findings suggest that the influence of the
      environment can be neutral, enabling, or disabling depending on the global scores
      or level of analysis being considered.

PMID- 17453977
TI  - Is there a relationship between light touch-pressure sensation and functional
      hand ability?
AB  - PURPOSE: To investigate and compare the level of light touch-pressure sensation
      as tested via the Semmes Weinstein monofilament (SWM) test with the level of
      functional hand ability. METHODS: Twenty-seven persons with isolated sensory
      deficit due to leprosy and 31 healthy controls were tested in the Occupational
      Therapy department of a hospital for patients with Hansen's disease. Palmar light
      touch thresholds were determined by SMW testing. Functional hand ability was
      tested via the Jebsen-Taylor Hand Function Test (JTHFT) and the Functional
      Dexterity Test (FDT). All participants were measured by manual muscle testing
      (MMT) to exclude any motor impairment. Data analysis compared sensory thresholds
      and level of functional hand ability between the two groups and examined the
      relationship between the variables. RESULTS: In the group with sensory deficit,
      the sensory thresholds were significantly higher than in the control group.
      Significant correlations were found between the sensory thresholds measured by
      the SWM test and the FDT and JTHFT scores, with higher correlations found for
      tasks entailing manipulation of small objects. CONCLUSIONS: The findings support
      the existence of a relationship between sensory light touch thresholds tested by
      the Semmes Weinstein monofilaments (SWMs) and hand function. However, the SWM
      test alone is not sufficient as an indicator of hand function and must therefore
      be supplemented with other hand function tests.

PMID- 17453978
TI  - Physical capacity tasks in chronic low back pain: what is the contributing role
      of cardiovascular capacity, pain and psychological factors?
AB  - PURPOSE: To explore the association of personal and body functions with physical
      capacity tasks used in the evaluation of chronic low back pain (CLBP) treatment.
      METHOD: Cross-sectional study in which 221 patients with non-specific CLBP
      participated. Physical capacity was assessed by six capacity tasks, and several
      personal and body functions were assessed by questionnaires (age, gender, pain
      intensity, duration of pain, radiating pain to leg, fear of injury/movement,
      depression, pain catastrophizing and internal control of pain). Cardiovascular
      capacity was measured by a modified Astrand submaximal bicycle test. The
      association of these hypothetically influential personal and body function
      factors with capacity tasks was examined with multiple linear regression
      analyses. RESULTS: The total explained variance was low to moderate (9 - 19%),
      except for stair climbing for which the variance just reached 30%. Many putative
      factors did not contribute significantly to the level of outcome of several
      different tasks. CONCLUSIONS: Cardiovascular capacity, pain intensity, fear of
      injury/movement, cognitions, and depression had statistically significant but
      clinically minor effects on several, but not all capacity tasks. Radiating pain,
      age and duration of complaints had no significant influence at all. Due to
      anthropometric differences men outperformed women on most tasks. Apparently the
      influence of many personal, physical but especially psychological factors on the
      selected capacity tasks is not high at all. This might indicate that these tasks
      are more objectively measuring physical capacity than expected.

PMID- 17453979
TI  - Experiences of living with chronic back pain: the physical disabilities.
AB  - PURPOSE: Back-related functional limitations are largely assessed using lists of
      activities, each scored on a yes/no basis and the scores then summed. This
      provides little information about how chronic back pain (CBP) patients live with
      their condition. This study describes the consequences of living day-to-day with
      CBP and documents the 'insider' accounts of its impact on daily life. METHOD:
      Unstructured interviews, using the 'Framework' approach with topic guide, were
      recorded and transcribed verbatim. Subjects were sampled for age, sex, ethnicity
      and occupation from new referrals with back pain to a rheumatology outpatient
      clinic. Eleven subjects (5 male, 6 female) were interviewed either in English (n
      = 9) or their preferred language (n = 2). Interviews were read in-depth twice to
      identify the topics. Data were extracted in phrases and sentences using thematic
      content analysis. RESULTS: Four themes emerged: sleep/rest, mobility,
      independence and leisure. All subjects reported issues about sleep and rest, nine
      about mobility, seven about independence and six on leisure. Most descriptions
      concerned loss and limitation in daily life. Strategies for coping with sleep
      disruption and physical limitations were described. CONCLUSIONS: Subjects
      provided graphic 'in-depth' descriptions of experiences living with CBP every
      day; expressed regret at the loss of capabilities and distress at the functional
      consequences of those losses. Facilitating 'adjustment' to 'loss' may be more
      helpful than inferring the potential for a life free of pain as a result of
      therapeutic endeavours.

PMID- 17453980
TI  - Integrated care for MS patients.
AB  - PURPOSE: The problem of complex healthcare to MS patients, together with the
      rising prevalence of MS and escalating costs, has caused healthcare policy makers
      to consider innovative approaches to controlling costs and improving the quality
      of care. An integrated care approach may provide a means for better coordination
      and delivery of care. The aim is to review recent integrated care initiatives and
      their significance for MS patients. METHOD: A literature search was conducted to
      trace relevant literature on integrated care for MS patients published between
      1995 and 2003. RESULTS: Although integrated care appears to offer potential for
      eliminating fragmentation and discontinuity in healthcare for MS patients, there
      are few published studies which have evaluated its implementation with MS
      patients. CONCLUSIONS: Even though the potential advantages of integrated care
      are well known, the applicability of this approach for MS patients has still to
      be demonstrated.

PMID- 17453982
TI  - Effectiveness of workplace rehabilitation interventions in the treatment of work
      related low back pain: a systematic review.
AB  - PURPOSE: A systematic review was conducted to evaluate the effectiveness of
      workplace rehabilitation interventions for injured workers with low back pain
      (LBP). METHOD: MEDLINE, CINAHL (Cumulative Index to Nursing and Allied Health
      Literature), EMBASE, and AMED (Allied and Complementary Medicine) were searched
      from 1982 to 2005 for peer-reviewed studies of rehabilitation interventions that
      were provided at the workplace to workers with musculoskeletal work-related LBP.
      Methodological quality appraisal and data extraction were conducted by five
      reviewers. RESULTS: Of a total of 1,224 articles that were identified by the
      search, 15 articles, consisting of 10 studies, were of sufficient quality to be
      included in the review. The best evidence was that clinical interventions with
      occupational interventions as well as early return to work/modified work
      interventions were effective in returning workers to work faster, reducing pain
      and disability, and decreasing the rate of back injuries. Ergonomic interventions
      also were found to be effective workplace interventions. CONCLUSION: The need for
      further research in this area is necessary to reduce the burden of back pain on
      employees and their families, employers, and the health care system.

PMID- 17453983
TI  - Masculine role variables and outcomes among men with spinal cord injury.
AB  - PURPOSE: Few studies have considered the impact of masculine role variables on
      outcome and adjustment to SCI among men. The present study examined the relations
      among SCI, views of masculinity, psychological adjustment, and rehabilitation
      outcomes among men with SCI. METHOD: The sample included 20 men with SCI
      receiving inpatient rehabilitation, with a mean age of 45 years. Data included
      demographic variables as well as Conformity to Masculine Norms Inventory (CMNI),
      Gender Role Conflict Scale (GRCS), Functional Independence Measure (FIM), and
      Satisfaction with Life Scale ratings, and change in marital status. RESULTS: The
      findings revealed that satisfaction with life was positively related to scores on
      the CMNI Violence scale, FIM change from admission to discharge was positively
      related to the CMNI Emotional Control scale and negatively related to the CMNI
      Dominance scale. Change in marital status was inversely related to the CMNI
      Emotional Control and Primacy of Work scales and the GRCS Restricted Emotionality
      and Power, Success, and Competition scales. CONCLUSIONS: The findings show that
      certain aspects of the traditional masculine role (i.e., ability to modulate
      strong emotions) may be adaptive in the rehabilitation process, whereas other
      aspects (i.e., a dominant interpersonal style) may present a barrier to effective
      rehabilitation.

PMID- 17453984
TI  - A comparison of a hospital-based and two home-based rehabilitation programmes.
AB  - PURPOSE: This paper compares the service models of three different types of
      rehabilitation programmes provided in Victoria, Australia: One hospital-based and
      two types of rehabilitation in the home (RITH). METHOD: Nine focus group
      interviews were conducted with multidisciplinary staff working in rehabilitation
      teams in one hospital-based and eight RITH programmes. Additional data were
      collected for 164 clients and 75 carers from eight of these programmes at
      admission, discharge and three months post discharge. Interviews were conducted
      with 32 clients and 14 carers. RESULTS: The criteria for admission and model of
      rehabilitation adopted in the three programmes were similar. There were
      differences in programme aims, characteristics of the clients admitted and the
      type and level of therapy clients received, both between hospital and home-based
      programmes and between the three programmes. In general, staff and clients saw
      the home as providing a relevant context that enabled individualized, goal
      directed therapy for medically stable rehabilitation clients. The hospital
      offered an opportunity to socialize with others and specialized equipment.
      CONCLUSIONS: Results of this study suggest clients and carers require a mix of
      hospital and home-based rehabilitation that is able to respond to their needs and
      preferences at each phase of the rehabilitation continuum.

PMID- 17453985
TI  - Physiological cost index (PCI) and walking performance in individuals with
      transfemoral prostheses compared to healthy controls.
AB  - PURPOSE: Uncomplicated methods for evaluation of prosthetic walking performance
      for individuals with lower limb amputations are valuable. The Physiological Cost
      Index (PCI), the comfortable walking speed (CWS) and self-reported walking
      distances are three examples of such measures. The aim was to obtain values for
      these measures for individuals walking with transfemoral prostheses and to
      compare the results with healthy controls. METHOD: Individuals with an
      established transfemoral amputation for reasons other than vascular disease (TFA
      group, n = 41, 30 male/11 female, mean age 49, SD 11.5) were compared to age-and
      gender matched healthy controls (Healthy group, n = 22). PCI was assessed walking
      in CWS for 5 min and self-reported distances accomplished outdoors was assessed
      with the Walking Habit Score (0 - 100). RESULTS: Mean PCI was 0.55 (SD 0.19) in
      the TFA-group and 0.31 (SD 0.09) in the Healthy group (p < 0.001). The CWS was 62
      (SD 12.6) and 90 (SD 12.8) m/min and the Walking Habit Score 48 (SD 19) and 74
      (SD 16) score-points respectively (p < 0.001). CONCLUSIONS: By using
      uncomplicated and inexpensive methods, this study shows that walking with
      transfemoral prostheses is done with considerably increased energy cost, slower
      CWS and that limited walking distances outdoors are performed compared to healthy
      controls.

PMID- 17453986
TI  - Pain perception during the rehabilitation phase following traumatic hip fracture
      in the elderly is an important prognostic factor and treatment tool.
AB  - PURPOSE: To evaluate the role of pain perception on admission to geriatric
      rehabilitation on the functional recovery after rehabilitation treatment in
      elderly patients with hip fracture and on the length of stay. METHOD: One hundred
      and sixty-five community dwelling elderly 65-year-old and over (mean age of 78
      years), following recent operated traumatic hip fracture without clinical
      evidence for another acute medical or surgical condition were assessed regarding
      age, sex, chronic medical conditions, pre-fracture functional status, type of
      fracture and of operation, pain perception, and cognitive status. Pain was
      measured using the Visual Analogue Score (VAS). Functional status was measured
      using the Functional Independence Measurement (FIM). Activities of Daily Living
      (ADL) were assessed using the Katz index. RESULTS: The average VAS score on
      admission was 7.38 +/- 1.20 and on discharge 3.67 +/- 1.18. Pain on admission
      inversely correlated to family support, function prior to fracture and cognitive
      status on admission, and correlated positively with depressed mood. With every
      increase of one point in VAS on admission above 4 points, the FIM on discharge
      decreased by 8.77 and the length of stay increased by 4.76 days. CONCLUSIONS:
      Pain intensity may add a valuable dimension for the prognostic evaluation of the
      patients with hip fractures. Inadequate early patient assessment and associated
      treatment impact on the patients' functional outcome, prolonged duration of
      rehabilitation treatment, and therefore, in addition to socio-economic effect,
      increase the cost to the local health care setting.

PMID- 17453987
TI  - Computerized gait analysis of botulinum toxin treatment in children with cerebral
      palsy.
AB  - PURPOSE: Intramuscular botulinum toxin A (BTA) injection is a local reversible
      treatment with a wide range of therapeutic applications, including temporary
      reduction of spasticity. The aim of this work was a quantitative, computerized
      objective evaluation of BTA-induced improvement of the walking functional ability
      in a group of children with cerebral palsy (CP). METHODS: Fifteen children with
      CP and 20 healthy children were evaluated. All patients were equinus walkers
      without fixed contractures of triceps surae muscles and they were evaluated
      before and after about 1.5 months from BTA injections into the calf muscles. The
      effectiveness of treatment was evaluated by 3D computerized gait analysis.
      RESULTS: Data analysis revealed a significant improvement of equinus foot and
      ankle range of motion during gait after BTA injection. Positive effects were
      evident also at the knee joint as documented by the improvement of kinetics
      characteristics (moment and power). CONCLUSIONS: Computerized gait analysis is a
      valid method for quantification of BTA effect on walking in children with CP,
      allowing a detailed evaluation of improvement at each joint and a quantitative
      evaluation of treatment outcome.

PMID- 17453988
TI  - The availability of allied health care in nursing homes.
AB  - PURPOSE: To determine the availability of allied health care in nursing homes in
      the Netherlands, and its dependency on characteristics of the nursing home.
      METHODS: Structured surveys by telephone were carried out in a sample of 100 from
      a country total of 286 somatic (for somatic patients only) and combined (with
      units for both somatic and psychogeriatric patients) nursing homes. Multiple
      linear regression analyses were performed to determine relationships between the
      availability of care and the type of nursing home, its country location
      (urban/non-urban) and the presence of specific wards/units within the nursing
      home. RESULTS: Physiotherapy and occupational therapy were present in almost all
      nursing homes (99% and 93% respectively); 92% of the nursing homes offered speech
      and language therapy and 88% had dietetics available. Average availability rates
      were: 2.16 full time equivalents per 100 beds/places for physiotherapy, 0.96 for
      occupational therapy, 0.38 for speech- and language therapy and 0.18 for
      dietetics. Somatic nursing homes and nursing homes with stroke-units, day-care,
      or outpatient care present, had higher availability rates on allied health care.
      CONCLUSIONS: Allied health care disciplines varied in terms of full-time
      equivalents per 100 beds/places. Per discipline also a wide variation exists in
      full-time equivalents per 100 beds/places among all participating nursing homes,
      regardless of their type. Characteristics of nursing homes had small effects on
      availability rates. International research is recommended in order to compare
      data and eventually reach consensus on optimal availability rates of allied
      health care in nursing homes, tuned to the demand.

PMID- 17453989
TI  - The Papworth Early Rehabilitation Programme: vocational outcomes.
AB  - BACKGROUND: There are 2.7 million people in the UK receiving incapacity benefits,
      costing approximately pound 18 billion pa. Government has adopted a policy of
      helping claimants back into work, through structured vocational rehabilitation
      schemes. There are no published results of vocational rehabilitation services in
      the UK. We present the results of the Papworth Trust vocational rehabilitation
      programme. Depending on the severity of their disability, the 'Early Rehab
      Programme' aims to get people on incapacity benefits: (a) into employment, (b)
      fit for and seeking work, (c) involved in voluntary work, (d) education, or (e)
      able to live independently. METHODS: Retrospective chart survey and telephone
      follow up. SETTING: Cambridgeshire. RESULTS: Since 1995, 274 people attended for
      a preliminary interview, of which 107 subsequently started a full rehab
      programme. Eighty-seven were male and 20 female. Half had been unemployed for
      more than two years. Ninety-four completed the programme, of whom 53 had gained
      employment, 33 were 'work ready' and four were doing voluntary work. At long-term
      follow-up, 52 were employed, 12 were in voluntary work, and 7 had retired on
      medical grounds. CONCLUSIONS: This programme demonstrates that long-term
      Incapacity Benefit recipients can return to sustained employment, as shown in
      those who participated in the Papworth Trust's vocational rehabilitation
      programme.

PMID- 17453990
TI  - The effect of spasticity, sense and walking aids in falls of people after chronic
      stroke.
AB  - OBJECTIVE: To study the effects of spasticity, sensory impairment, and type of
      walking aid on falls in community dwellers with chronic stroke. METHODS:
      Functional Independence Measure (FIM) Instrument, Joint Position Sense Evaluation
      (JPS), the Rivermead motor assessment scale (RMA), Ashworth Scale, Tinetti
      Assessment Tool were used to assess 100 cases. RESULTS: Fifty-three of the cases
      were grouped as nonfallers, 36 as one-time fallers and 11 as repeat fallers.
      These 3 groups were found to be different from each other in respect to FIM,
      Tinetti test and RMA (p < 0.001). In respect to knee JPS, nonfallers and one-time
      faller groups were found to be different from repeat fallers (p = 0.001). There
      is a difference among the groups in respect to Ashworth assessment (p < 0.001),
      use of walking aid (p = 0.01) and type of walking aid (p = 0.01). Some 43% of the
      cases use a walking aid (58.1% cane, 41.9% high cane). According to Ordinal
      logistic regression analysis, it was found that the possibility of fall increased
      (p < 0.01), as the value of spasticity increased while the possibility of the
      fall of the individuals with stroke decreased (p < 0.00 - 0.01) as Tinetti, RMA
      and FIM variables increased. CONCLUSIONS: In respect to falls, spasticity is also
      an indicator for chronic stroke patients, as is motor impairment, functional
      situation, impairment of balance and walking. Sensory impairment, using a walking
      aid and the type were found to be ineffective.

PMID- 17453991
TI  - The development of a short questionnaire for screening of activity limitation and
      safety awareness (SALSA) in clients affected by leprosy or diabetes.
AB  - PURPOSE: The purpose of this study was to develop and validate a method of
      measuring activity limitation in leprosy and diabetes. The resulting
      questionnaire should be quick and simple to use in basic clinical settings, not
      require any testing skills or equipment, be validated across a number of cultures
      in order to be widely applicable, be relevant for anyone with long-standing
      peripheral neuropathy and be sensitive to changes in clients' capabilities.
      Because of impaired sensibility in hands or feet, persons affected by leprosy or
      diabetes are expected to be aware that many activities carry a risk of injury,
      particularly repetitive stress, excess pressure, friction or burns. They are
      expected to avoid these risky activities, or modify how they are carried out, in
      order to prevent injury. An additional aim of the study was therefore to find
      ways of assessing how far clients were aware of safety issues and how much they
      limited their activities voluntarily because of safety concerns. METHOD: Lists of
      activities of daily living relevant for the target populations were generated
      through individual interviews and focus group discussions. A questionnaire of 374
      items was compiled and administered to 436 persons affected by leprosy and 132
      affected by diabetes in five countries in four continents. A total of 76% of
      respondents had impairments. Occupational therapists not otherwise involved in
      this study gave an independent assessment of the degree of activity limitation of
      207 respondents. The process of item selection from this database is presented
      step by step. Items for the SALSA scale were practised by at least 70% of
      respondents in all participating populations, were easy to perform for some but
      difficult for others, correlated well with the assessment of independent
      practitioners and had good item-total correlation. The present set of 20 items is
      well represented by a single principal component and had a high scale reliability
      coefficient. RESULTS: On a 20-item scale, one would expect a score of 20 if the
      respondents practiced all the activities listed without difficulty. Higher scores
      reflect increasing activity limitation. The SALSA score varied from 10 to 75 with
      a mean of 32. The distribution of the scores was not different between men and
      women or between disease groups. There was a consistent increase of the SALSA
      score with age and with the level of impairment. Compared to India and Nigeria,
      the average SALSA scores, adjusted for age and impairment level, were higher in
      Israel and Brazil, but lower in China. The spearman correlation coefficient
      between the SALSA scores and the scores assigned by the independent experts was
      0.67. Among 23 respondents without overt disease, the SALSA score had a median of
      19 and half the respondents scored between 18 and 20. CONCLUSIONS: The present
      research has resulted in the SALSA scale, a short questionnaire which can be
      administered within 10 min and which provides a standardized measure of activity
      limitation in clients with a peripheral neuropathy. It can be used to make
      comparisons between (groups of) individuals in different countries and in the
      same person (or group) over time. General health workers can use SALSA to screen
      clients and refer those with high scores to specialised services. In addition,
      the scale will assist service providers in designing appropriate interventions.

PMID- 17453992
TI  - The QE Health Scale (QEHS): assessment of the clinical reliability and validity
      of a spiritually based holistic health measure.
AB  - PURPOSE: To assess the clinical reliability and validity of a holistic health
      measure, the QE Health Scale (QEHS), for use with people with physical
      disabilities. METHOD: A test-retest design saw the QEHS administered and compared
      with established measures of health at admission and discharge from three-week
      inpatient rehabilitation programmes. Data was analysed by factor and correlation
      analysis. Clinician-reported credibility and usefulness of the theoretical basis
      of the QEHS, the QEHS itself, and Patient Profiles derived from the QEHS were
      also used to evaluate clinical validity. RESULTS: The QEHS was judged to possess
      satisfactory reliability and validity. CONCLUSION: The QEHS is a clinically
      reliable, valid, credible and useful holistic health instrument to facilitate
      client-centred therapeutic interventions, inform decision-making and evaluate
      outcomes for people with physical disabilities.

PMID- 17453993
TI  - Referral of patients with neuromuscular disease to occupational therapy, physical
      therapy and speech therapy: usual practice versus multidisciplinary advice.
AB  - PURPOSE To compare the volume of occupational therapy (OT), physical therapy (PT)
      and speech therapy (ST) as currently received by patients with neuromuscular
      diseases with the volume of OT, PT and ST recommended by a multidisciplinary
      team. METHOD: The use of OT, PT and ST was studied retrospectively and
      prospectively in a reference group (n = 106) receiving usual care and in an
      intervention group (n = 102) receiving advice based on multidisciplinary
      assessments. A cost analysis was made and the implementation of the advice was
      evaluated at 6 months. INTERVENTION: Multidisciplinary assessments consisted of a
      single consultation by OT, PT and ST each, followed by a multidisciplinary
      meeting and integrated advice. OUTCOME VARIABLES: Volume (frequency times
      duration) of therapy, relative over- and underuse of therapy and costs of therapy
      and intervention. RESULTS: Compared to the multidisciplinary advice, there was
      40% underuse of OT among patients with neuromuscular disease. For PT, there was
      32% overuse and 22% underuse; for ST, there was neither over- nor underuse. Some
      40% of patients received once-only advice regarding ST compared to 27% regarding
      OT and 19% regarding PT. The costs of the multidisciplinary advice were estimated
      at euro245 per patient. If fully implemented, our multidisciplinary approach
      would result in a mean cost savings of euro85.20 per patient. The recommended
      therapy had, however, been implemented only partially at 6 months follow-up.
      CONCLUSIONS: Some patients with a neuromuscular disease do not receive any form
      of allied healthcare, whereas they should. Among patients with neuromuscular
      disease who do receive some form of allied healthcare, quite a few receive these
      treatments for too long periods of time. Ways need to be developed to improve
      implementation of the multidisciplinary advice and to obtain a more favourable
      balance between its costs and benefits.

PMID- 17453994
TI  - Gait in the water: a comparison between young and elderly subjects.
AB  - PURPOSE: To find differences, if any, between young and elderly people who walked
      in a pool. METHOD: Twenty young subjects (mean age 23.8 years, SD 3.6) and 20
      elderly subjects (mean age 66.8, SD 3.8) were enrolled in a cross-sectional
      design study. Gait parameters were assessed by means of underwater video
      recording. Analysis of the playback allowed the assessment of speed, stance and
      swing duration with the aid of a digital clock with a 0.04% resolution. Length of
      step was also measured. Two-tail Student's t-test and Pearson's correlation
      coefficient were applied. RESULTS: The mean speed was 1482 meters per hour (SD
      207) in the younger population and 1366 meters per hour (SD 336) in the elderly.
      The mean stance duration was 1.60 s (SD 0.26) in the younger population and 1.59
      s (SD 0.34) in the elderly. The mean swing duration was 1.16 s (0.22) in the
      younger population and 1.02 s (SD 0.26) in the elderly. The mean step length was
      0.41 m (SD 0.05) in the younger population and 0.37 (SD 0.09) in the elderly.
      None of the differences was statistically significant. CONCLUSIONS: Gait in
      elderly people who walk in the water retains characteristics that are typical of
      younger participants. Hydrotherapy is therefore a suitable intervention for old
      people who are in a good state of fitness.

PMID- 17453995
TI  - Gait in the early days after total knee and hip arthroplasty: a comparison.
AB  - PURPOSE: To evaluate whether gait after Total Knee Arthroplasty (TKA) is
      different from gait after Total Hip Arthroplasty (THA) in the early days
      following surgical intervention. METHOD: The gait was studied in water, thus
      exploiting its buoyancy force. Twenty consecutive patients underwent TKA and
      twenty consecutive patients underwent THA. The mean age was 70.2 years (SD 6.9).
      Twenty age-matched volunteers were the control group. RESULTS: At the beginning
      TKA and THA patients had the same speed and the same step length. At day 15 there
      was a speed difference in favour of THA patients (t = - 2.245, df 38, p = 0.031).
      Likewise, the step length was longer in THA patients (t = -2.293 df 38, p =
      0.027). In contrast to TKA patients, THA patients were unbalanced, having a
      longer stance phase on the non-operated leg and a longer swing on the
      contralateral one. CONCLUSIONS: Gait strategies were completely different after
      TKA and THA interventions. TKA patients were balanced over their feet and they
      appeared more cautious and more concerned about gait quality than moving quickly.
      By contrast, THA patients were unbalanced, having a longer stance phase on the
      non-operated leg and a longer swing on the contralateral one. However, their
      speed gain was higher.

PMID- 17453996
TI  - Gait during hydrokinesitherapy following total knee arthroplasty.
AB  - PURPOSE: To obtain gait parameters during hydrotherapy (HT) in patients who were
      referred for rehabilitation after primary total knee arthroplasty (TKA). METHOD:
      The study had a cohort prospective design. Patients who had undergone TKA
      followed a HT rehabilitation programme. Twenty-two consecutive patients were
      enrolled. Four of them dropped out for various reasons, independently of HT.
      Therefore 18 patients could be evaluated (5 men and 13 women). Eighteen age
      matched healthy volunteers were the control subjects. Nine patients had a right
      TKA and nine a left TKA. On the average HT duration was 18.4 days (SD 1.4).
      RESULTS: The patients presented with a mean speed of 912 (SD 275) meters per hour
      (m/h) at the baseline. At the last session the mean speed was 1330 (SD 416) m/h.
      The mean stance duration was 1.75 s (SD 0.34) on the operated side and 1.83 s (SD
      0.41) on the non-operated side. By contrast, the mean swing duration was 1.10 s
      (SD 0.25) on the operated side and 1.13 s (SD 0.34) on the non-operated side. The
      step duration was the same on both sides. At the beginning of HT the mean
      stance/swing ratio was 1.94 on the operated side, whereas it was 1.77 on the non
      operated side. In the controls the ratio was 1.46. At the beginning the mean
      stride length was 0.526 m (SD 0.147) and the value became 0.556 (SD 0.138) after
      18 training sessions. At the individual level, recovery occurred in a non-linear
      fashion (Best Fitting, 7th-grade Fourier finite series). CONCLUSIONS: The study
      design permits accurate definition of stride parameters during rehabilitation
      which allows optimization of the programme. Increase in speed and regain of
      balance are the main targets of a HT programme and are monitored on a daily
      basis.

PMID- 17453997
TI  - Gait during hydrokinesitherapy following total hip arthroplasty.
AB  - PURPOSE: To obtain gait parameters during hydrotherapy (HT) in patients who were
      referred for rehabilitation after total hip arthroprostheses. METHOD: The study
      had a cohort prospective design. Patients who underwent primary total hip
      arthroplasty (THA) followed a HT rehabilitation program. Twenty-one consecutive
      patients were enrolled. Five of them dropped out for various reasons,
      independently of HT. Therefore 16 patients could be evaluated (5 men and 11
      women). Sixteen age-matched healthy volunteers were the control subjects. Nine
      patients had a right THA and 7 a left THA. On average HT duration was 15.7 days
      (SD 3.8). RESULTS: The patients presented with a mean speed of 749 meters per
      hour (SD 146) at the baseline. At the last session the mean speed was 1175 meters
      per hour (SD 396). The mean stance duration was 1.59 s (SD 0.28) on the operated
      side and 1.67 (SD 0.27) on the non-operated side. By contrast, the mean swing
      duration was 1.02 s (SD 0.20) on the operated side and 0.95 s (SD 0.16) on the
      non-operated side. The differences in balance were statistically significant. The
      step duration was the same on both sides. At the beginning of HT the stance/swing
      ratio was 1.62 (SD 0.40) on the operated side, whereas it was 1.74 (SD 0.42) on
      the non-operated side. In the controls the ratio was 1.45. During HT both values
      fluctuated but the trend was toward a better coherence over time. At the
      beginning the mean stride length was 0.484 meters (SD 0.116) and the value became
      0.628 (SD 0.131) after 15 training sessions. At the individual level, recovery
      occurred in a non-linear fashion, but the mean regression line had a coefficient
      of 27.1 and the intercept was at 560.3. CONCLUSIONS: The study design permits
      accurate definition of stride parameters during rehabilitation which allows
      optimization of the programme. Increase in speed and regain of balance are
      monitored on a daily basis and they appear as the targets of a HT programme.

PMID- 17453998
TI  - Crossing professional and organizational boundaries: the implementation of
      generic rehabilitation assistants within three organizations in the northwest of
      England.
AB  - PURPOSE: New generic support worker roles are being developed within
      rehabilitation and intermediate care services throughout the UK, as a consequence
      of staff shortages and the policy drive to look at new ways of working to meet
      the needs of older people. This paper describes a joint project between a Primary
      Care Trust, an Acute Trust and Social Services in one region in the northwest of
      England. It aims to describe the process of introducing new roles within
      rehabilitation and evaluates the acceptability and integration within different
      settings. METHODS: Thirty support worker staff from an Acute Trust, Primary Care
      Trust and Social Services were trained over a period of 18 months to become
      generic Rehabilitation Assistants (RAs). A total of 55 semi-structured interviews
      of patients, associated professionals and RAs were conducted to examine the
      acceptability and integration of the new role. The interviews were tape-recorded,
      concurrently transcribed, inductively analysed and categorized into themes.
      RESULTS: Several factors appeared to influence the acceptance and integration of
      the new role, namely: Prior experience and the degree of role change, familiarity
      and inter-staff relationships, role distinction and contribution and resources
      and management. Despite many challenges, patients, professionals and the RAs
      reported huge appreciation of the new role. CONCLUSIONS: The evaluation
      demonstrates how an innovative, inter-organizational approach can deliver new
      solutions to address workforce issues. Further research is recommended
      nationally, to track the development and evaluate the effectiveness of similar
      roles.

PMID- 17453999
TI  - Characterization of AP3B2_v2, a novel splice variant of human AP3B2.
AB  - A novel splice variant of human AP3B2, named AP3B2_v2, was isolated through the
      large-scale sequencing analysis of a human fetal brain cDNA library. The AP3B2_v2
      cDNA is 1171 bp in length. Sequence analysis revealed AP3B2_v2 missed 22 exons
      that existed in AP3B2_v1, leading to a different putative protein. The deduced
      proteins were 145 amino acids (designated as AP3B2_v2) and 1082 amino acids
      (AP3B2_v1) in length, sharing the C-terminal 145 amino acids. RT-PCR analysis
      showed that human AP3B2_v2 were expressed in several human adult tissues
      analyzed. The expression levels of AP3B2_v2 were relatively high in brain and
      testis. In contrast, low levels of expression were detected in kidney, pancreas,
      spleen, thymus, prostate, ovary and small intestine.

PMID- 17454000
TI  - The complete mitochondrial genome of the Senegal sole, Solea senegalensis Kaup.
      Comparative analysis of tandem repeats in the control region among soles.
AB  - The complete nucleotide sequence of the mitochondrial genome for the Senegal sole
      Solea senegalensis Kaup was determined. The mitochondrial DNA was 16,659 base
      pairs (bp) in length. Sequence features of the 13 protein-coding genes, two
      ribosomal RNAs and 22 transfer RNAs are described. The non-coding control region
      (1017 bp) was compared with those of the closely related soles Solea solea and
      Solea lascaris. The typical conservative blocks were identified. A cluster of 42
      and 22 tandemly arrayed repeats was detected near the 3' end of control region in
      S. solea and S. lascaris, respectively. On the contrary, only two (93.8% of
      haplotypes) or three copies (6.2%) of an 8-bp repeated sequence motif was found
      in S. senegalensis. Phylogenetic analysis showed that 7 out of 9 of haplotypes
      bearing three copies grouped in a separate cluster. Possible mechanisms
      influencing the evolution of control region among soles are discussed.

PMID- 17454001
TI  - Cloning and sequence analysis of Hemonchus contortus HC58cDNA.
AB  - The complete coding sequence of Hemonchus contortus HC58cDNA was generated by
      rapid amplification of cDNA ends and polymerase chain reaction using primers
      based on the 5' and 3' ends of the parasite mRNA, accession no. AF305964. The
      HC58cDNA gene was 851 bp long, with open reading frame of 717 bp, precursors to
      239 amino acids coding for approximately 27 kDa protein. Analysis of amino acid
      sequence revealed conserved residues of cysteine, histidine, asparagine,
      occluding loop pattern, hemoglobinase motif and glutamine of the oxyanion hole
      characteristic of cathepsin B like proteases (CBL). Comparison of the predicted
      amino acid sequences showed the protein shared 33.5-58.7% identity to cathepsin B
      homologues in the papain clan CA family (family C1). Phylogenetic analysis
      revealed close evolutionary proximity of the protein sequence to counterpart
      sequences in the CBL, suggesting that HC58cDNA was a member of the papain family.

PMID- 17454002
TI  - Sequence analysis of a human RhoGAP domain-containing gene and characterization
      of its expression in human multiple tissues.
AB  - Rho GTPase activating proteins (GAPs) stimulate the intrinsic GTP hydrolysis
      activity of Rho family proteins. Here we isolated a rhoGAP domain-containing
      protein gene with the same reading frame with ARHGAP19 gene, which has an ORF of
      1485 bp encoding a putative protein of 494 amino acid residues with a predicted
      molecular mass of 55.806 kDa. Protein pattern analysis shows that it contains a
      bipartite nuclear localization signal (NLS) besides the rhoGAP domain, and it is
      consistent with the result of sub-cellular localization. ARHGAP19 is located in
      chromosome 10q24.1 and consists of 12 exons according to the Blastn result. Weak
      expression was detected in adult pancreas, spleen, thymus and ovary of the 16
      adult tissues examined, while it had a more abundant expression pattern in eight
      important human fetal tissues. The expression pattern of ARHGAP19 shows it may
      have functions related to fetus development and gives us some clues on its
      probable functions in adult tissues.

PMID- 17454003
TI  - Fine mapping of murine asthma quantitative trait loci and analyses of Ptgs1 and
      Mrc1 as positional candidate genes.
AB  - Asthma is a common respiratory disease that is driven by both genetic and
      environmental factors. Identification of the genes underlying asthma will provide
      insight into the mechanisms and treatment of this important disease. Previous
      studies in this laboratory identified two distinct quantitative trait loci for
      the asthma-related parameter, allergen-induced airway hyperresponsiveness, in a
      murine model by means of a genome-wide linkage analysis. The present study
      focuses and refines the map location of these two loci. Additionally, we explore
      prostaglandin-endoperoxide synthase-1 (Ptgs1) and mannose receptor C-type 1
      (Mrc1) genes as two new positional candidate genes for allergen-induced airway
      hyperresponsiveness through comparative sequence analysis and mRNA expression
      studies of mouse strains with genetically mediated airway responsiveness.

PMID- 17454004
TI  - Isolation and characterization of a lectin gene from seeds of chickpea (Cicer
      arietinum L.).
AB  - A cDNA library was constructed in lambda TriplEx2 vector using poly (A(+)) RNA
      from immature seeds of Cicer arietinum. The lectin gene was isolated from seeds
      of chickpea through library screening and RACE-PCR. The full-length cDNA of
      Chichpea seed lectin(CpGL)is 972 bp and contains a 807 bp open reading frame
      encoding a 268 amino acid protein. Analysis shows that CpSL gene has strong
      homology with other legume lectin genes. Phylogenetic analysis showed the
      existence of two main clusters and clearly indicated that CpSL belonged to
      mannose-specific family of lectins. RT-PCR revealed that CAA gene expressed
      constitutively in various plant tissues including flower, leaf, root and stem.
      When chickpea lectin mRNA level was checked in developing seeds, it was higher in
      10 DAF seeds and decreased throughout seed development.

PMID- 17454005
TI  - Sequencing of cDNA and proximal promoter of equine hexokinase II gene.
AB  - In order to investigate the utilization of glucose in equine skeletal muscle, we
      determined the coding and proximal promoter sequences of the hexokinase type II
      (HKII) gene in thoroughbred horse, Grevy's zebra and Hartmann's mountain zebra.
      The deduced amino acid sequence of thoroughbred horse HKII showed 100, 100, 94.4,
      92.7 and 92.6% identities with Grevy's zebra, Hartmann's mountain zebra, human,
      mouse and rat HKIIs, respectively. In equine HKIIs, specific amino acid
      substitutions, Ile 159 and Arg 610, were found in the potential binding site for
      glucose. In addition, the nucleotide sequence of the equine proximal promoter has
      a number of conserved putative binding sites for transcription factor.

PMID- 17454006
TI  - Characterisation of the genomic canine Fgf8 locus and screen for genetic variants
      in 4 dogs with different face types.
AB  - We are investigating the genetic basis of morphological differences in skull
      shape between domestic dogs of different breeds using a candidate gene approach
      to identify genes involved in the genetic regulation. One such candidate is Fgf8.
      Fgf8 is a signalling molecule important in the embryonic development and
      patterning of the craniofacial region. Mice conditional null for the expression
      of Fgf8 after E9.5 have a short foreface and a wide skull (Trumpp et al. 1999).
      Using a combination of bioinformatics and PCR cloning, we have characterised the
      genomic loci of the canine Fgf8 gene. Like the mouse homologue, it is composed of
      six exons and we also predict that like the mouse, there are eight alternative
      isoforms that are generated by alternative splicing events. We have identified a
      short 200 bp sequence upstream of the Fgf8 gene that is highly conserved between
      species and have predicted putative transcription factor binding sites using the
      Transfac database. Genetic analysis of 4 dogs with different skull types
      identified genetic variation. None of the variants however, were predicted to
      have any functional significance.

PMID- 17454007
TI  - Identification and characterization of single nucleotide polymorphisms in 6
      growth-correlated genes in porcine by denaturing high performance liquid
      chromatography.
AB  - The growth-correlated genes that are part of the neuroendocrine growth axis play
      crucial roles in the regulation of growth and development of pig. The
      identification of genetic polymorphisms in these genes will enable the scientist
      to evaluate the biological relevance of such polymorphisms and to gain a better
      understanding of quantitative traits like growth. In the present study, seven
      pairs of primers were designed to obtain unknown sequences of growth-correlated
      genes, and other 25 pairs of primers were designed to identify single nucleotide
      polymorphisms (SNP) using the denaturing high-performance liquid chromatography
      (DHPLC) technology in four pig breeds (Duroc, Landrace, Lantang and Wuzhishan),
      significantly differing in growth and development characteristics. A total of 101
      polymorphisms were discovered in 10,707 base pairs (bp) from six genes of the
      ghrelin (GHRL), leptin (LEP), insulin-like growth factor II (IGF-II), insulin
      like growth factor binding protein 2 (IGFBP-2), insulin-like growth factor
      binding protein 3 (IGFBP-3), and somatostatin (SS). The observed average
      distances between the SNP in the 5'UTR, coding regions, introns and 3'UTR were
      134, 521, 81 and 92 bp, respectively. Four SNPs were found in the coding regions
      of IGF-II, IGFBP-2 and LEP, respectively. Two synonymous mutations were obtained
      in IGF-II and LEP genes respectively, and two non-synonymous were found in IGFBP
      2 and LEP genes, respectively. Seven other mutations were also observed. Thirty
      two PCR-RFLP markers were found among 101 polymorphisms of the six genes. The SNP
      discovered in this study would provide suitable markers for association studies
      of candidate genes with growth related traits in pig.

PMID- 17454008
TI  - Phylogenetic analysis and expression pattern of the AmphiCaBP-like gene from
      amphioxus, encoding a novel member of the calmodulin-like subfamily.
AB  - We characterized a novel gene, AmphiCaBP-like, encoding a putative Ca(2 + )
      binding protein (CaBP) with three EF-hand motifs from amphioxus (Branchiostoma
      belcheri tsingtauense). It exhibits significant similarities with the calmodulin
      and troponin C proteins from other species. Results of phylogenetic analysis
      indicated that amphioxus AmphiCaBP-like falls on the base of the troponin C
      clade. It may be a novel member of the calmodulin-like subfamily. In situ
      hybridization and RT-PCR analysis showed that AmphiCaBP-like is expressed
      throughout early development except the stages around the blastula. From neurula
      stage onward, transcripts of the AmphiCaBP-like are detected in the neural plate,
      the neural tube, the differentiating somites and the splanchnopleure, as well as
      the epithelium of the pharynx and gut. It is also expressed in the presumptive,
      but not the well-developed notochord. In adult amphioxus, the transcripts are
      found in the epithelial cells of the gut and midgut diverticulus, the wall of
      coelom, the branchia, the neural cord and gonads.

PMID- 17454009
TI  - Human GPR107 and murine Gpr108 are members of the LUSTR family of proteins found
      in both plants and animals, having similar topology to G-protein coupled
      receptors.
AB  - Two new cDNAs, human GPR107 and murine GPR108, were cloned from mammalian lung
      that are members of a novel gene family encoding proteins that are predicted to
      have an amino-terminal hydrophobic signal peptide sequence, a long extracellular
      domain and a carboxy-terminal seven transmembrane domain (LUSTR domain) similar
      to GPCRs. The 18-exon human GPR107 gene is located at 9q34.2-3 and spans 86.4 kb
      and the cDNA encodes a 552 residue protein. The closely related, but not
      homologous, 17-exon murine Gpr108 gene is located at 17C-D and spans 12.8 kb. The
      murine Gpr108 cDNA encodes a 562 residue protein that has 49% identity to human
      GPR107. They are distantly related to two other genes, transmembrane protein 87A
      and 87B that encode LUSTR domain-containing proteins in the human genome. LUSTR
      proteins are also found in Drosophila, Saccharomyces and Arabidopsis, but are
      absent from bacteria, archaea and viruses. This suggests that GPCRs are present
      in higher plants.

PMID- 17454011
TI  - Methamphetamine alarm: are we forgetting what we know?

PMID- 17454010
TI  - Cloning, sequence analysis and homology modeling of a novel phospholipase A2 from
      Heterometrus fulvipes (Indian black scorpion).
AB  - We report the cloning and sequencing of group III phospholipaseA(2) from
      Heterometrus fulvipes (HfPLA(2)), Indian black scorpion. The cDNA sequence codes
      for the mature portion of the group PLA(2) of 103 amino acids. The sequence has
      85% identity with Mesobuthus tamulus (Indian red scorpion) PLA(2) and a 40%
      identity with bee venom PLA(2) and human group III PLA(2). Most of the essential
      features of group III PLA(2) like Ca(2+) binding loop and catalytic residues are
      conserved. Homology modeling was done with the known structure of group III bee
      venom PLA(2). All the secondary structural motifs and the disulfide bridges are
      as predicted. The variation like the replacement of aspartic acid residue with
      glutamic acid in the well known histidine-aspartic acid dyad is a rare feature.
      This is the first structural model report of an Indian black scorpion PLA(2).

PMID- 17454012
TI  - Hazardous alcohol consumption and other barriers to antiviral treatment among
      hepatitis C positive people receiving opioid maintenance treatment.
AB  - Amongst people on opioid maintenance treatment (OMT), chronic hepatitis C (HCV)
      is common but infrequently treated. Numerous barriers, including misuse of
      alcohol may limit efforts at anti-viral treatment. The aim of this study was to
      define barriers, including alcohol misuse, to the effective treatment of HCV
      amongst OMT recipients. Ninety-four OMT patients completed the 3-item Alcohol Use
      Disorders Identification Test (AUDIT-C). A semi-structured interview was used in
      53 subjects to assess alcohol use in detail, psychological health, discrimination
      and access to HCV treatment. Feasibility of brief intervention for alcohol misuse
      was assessed. Of the screening participants, 73% reported they were HCV positive.
      Of the detailed interview participants, 26% reported no drinking in the past
      month, but 53% scored 8 or more on AUDIT and 42% exceeded NHMRC drinking
      guidelines. Twenty subjects received brief intervention and among 17 re
      interviewed at one month, alcohol consumption fell by 3.1 g/day (p = 0.003).
      Severe or extremely severe depression, stress and anxiety were found in 57%, 51%
      and 40% of interviewees respectively. Episodic heavy drinking, mental health
      problems, perceived discrimination, limited knowledge concerning HCV were all
      common and uptake of HCV treatment was poor. Brief intervention for alcohol use
      problems was acceptable to OMT patients, and warrants further study.

PMID- 17454013
TI  - Clinical supervision in the alcohol and other drugs field: an imperative or an
      option?
AB  - There is a growing interest in Clinical Supervision (CS) as a central workforce
      development (WFD) strategy. This paper provides a definition of and rationale for
      CS, characterises its various forms, identifies selection and training issues,
      and advises on policy and implementation issues central to redressing
      shortcomings in supervision practice within the alcohol and other drugs (AOD)
      field. Relevant selective literature is reviewed. Key conceptual issues were
      identified, and strategies developed to address implementation barriers and
      facilitate relevant policy. There is a common conceptual confusion between
      administrative supervision and CS. Clarification of the role, function and
      implementation of CS is required. Priority issues for the AOD field include:
      enhancing belief in CS; ensuring adequate resource allocation; developing
      evaluation protocols; and addressing specific arrangements under which
      supervision should occur. CS has been underutilised to date but holds
      considerable potential as a WFD strategy. It is fundamental to workers'
      professional development, can contribute to worker satisfaction and retention,
      and may improve client outcomes. Critical next steps are to establish the
      generalisability to the AOD field of the benefits observed from CS in other
      disciplines, and evaluate longer-term gains of CS programs.

PMID- 17454015
TI  - Effective drug policy: a new approach demonstrated in the Drug Policy Modelling
      Program.
AB  - The aim of this paper is to describe a new comprehensive approach to studying
      illicit drug policy - one that integrates evidence, disciplinary approaches, drug
      use behaviours and policy making processes. The methods described here include
      systematic reviews of the evidence, studies of the ways in which policy decision
      making actually occurs, and the use of modelling approaches that can explicate
      the multi-dimensional nature of drug policy responses and their dynamic
      interactions. The approach described has the potential to facilitate new drug
      policy that would not have been possible or apparent through the sole study of
      one aspect of drug policy, such as the evidence-base or the political context or
      the economics of drug markets. We believe this approach may be more likely to
      produce strategic drug policy because it reflects the richness and complexity of
      the real world of drug use, and drug policy. The purpose of employing an
      integrative methodology is to create the potential for new drug policy insights,
      ideas and interventions - not restricted to one body of evidence, nor to
      accidental or fortuitous policy-making processes.

PMID- 17454014
TI  - Illegal drug-attributable morbidity in Canada 2002.
AB  - Use of illegal drugs is an important behavioral risk factor for burden of
      morbidity in developed countries. The objective was to estimate the number of
      diagnoses in acute care hospitals, psychiatric hospitalizations, admissions in
      specialized treatment, and number of days in treatment attributable to use of
      illegal drugs for Canada in 2002. The number of diagnoses in acute care
      hospitals, psychiatric hospitalizations, and hospital days were obtained from the
      Canadian Institute for Health Information (CIHI). Number of admissions and number
      of days in specialized inpatient and outpatient treatment of illegal drug
      dependency were obtained from provincial ministerial officials or drug addiction
      program coordinators. Except for effects of maternal use of drugs of addiction on
      the newborn, and suicide, drug-attributable fractions (DAFs) were estimated
      directly from available statistics in published literature. There were 61,026
      illegal drug-related diagnoses in acute care hospitals, 1,517 psychiatric
      hospitalizations, and 139,773 admissions to specialized treatment attributable to
      illegal drug use in Canada. The largest contributors were mental and behavioral
      disorders due to psychoactive substance use in acute care hospitals, and drug
      psychoses in psychiatric hospitalizations. Length of stay amounted to 352,121
      days in acute care hospitals, 31,508 days in psychiatric hospitals, and 2,851,829
      days in specialized treatment. Drug use constitutes a major contributor to burden
      of morbidity in Canada. Compared to 1992, the total number of illegal drug
      attributable days in 2002 increased, especially in acute hospitals by a factor of
      9.6. A mixture of prevention and harm reduction measures is proposed to reduce
      the burden of morbidity associated with drug use.

PMID- 17454016
TI  - Increasing socioeconomic inequalities in male cirrhosis of the liver mortality:
      Australia 1981-2002.
AB  - Liver cirrhosis mortality is an indicator of harms associated with high levels of
      alcohol consumption. There is good evidence that changes in political and
      economic systems can lead to changing patterns of liver cirrhosis mortality.
      Socioeconomic inequalities in liver cirrhosis mortality have been periodically
      reported but there are few studies of changes in socioeconomic inequalities in
      liver cirrhosis mortality over time. This paper examines changes in socioeconomic
      inequalities in liver cirrhosis mortality in Australia for the period 1981 -
      2002. Age standardised, liver cirrhosis mortality rates were calculated for
      occupational groupings for Australia 1981 - 2002. Occupations were grouped into
      non-manual and manual categories, and there was imputation for missing data.
      Despite decreasing overall liver cirrhosis mortality rates over time, liver
      cirrhosis mortality continues to account for about 3% of all deaths. Manual
      workers have consistently experienced liver cirrhosis mortality rates which are
      twice or more the rate experienced by non-manual workers. These inequalities
      appear to have increased in recent years and currently appear to be at historic
      highs (manual workers have mortality rates of about 2.5 times those of non-manual
      workers). Increasing socioeconomic inequalities in liver cirrhosis mortality in
      Australia suggest that lower SES groups have, over time, increased their level of
      harmful alcohol consumption relative to middle and higher SES groups. It is
      suggested that this might be attributed to a relative improvement in the
      affordability of alcohol over time.

PMID- 17454017
TI  - The use of psychoactive substances among medical students in southern Brazil.
AB  - The objective of our study was to investigate the patterns of use of psychoactive
      substances among students of a medical school in Southern Brazil and to explore a
      putative role of discrete behavioral and social variables in their drug use. This
      is a descriptive and transversal cut study. All regularly enrolled medical
      students at the University of Caxias do Sul were invited to participate in the
      study. A self-administered questionnaire, which analyses lifetime drug use as
      well as drug use in the previous 30 days and 12 months was utilized to collect
      data. From a total of 318 regularly enrolled students, 183 (57.5%) completed and
      returned the questionnaires. The highest prevalence rates of lifetime drug use,
      drug use in the last 12 months and drug use in the last 30 days were observed,
      according to drug type, as follow in descending order: alcohol, tobacco,
      marijuana, inhalants, tranquilizers, amphetamine and cocaine. A multivariate
      analysis indicated that research respondents who live with their parents as well
      as those whose parents live together harmoniously, those who deny close ties to
      drug users, those who disapprove drug use, those who are not tobacco smokers and
      those who manifest religious beliefs and practice presented the most reduced
      levels of illicit drug use. The use of psychoactive substances among medical
      students in the University of Caxias do Sul is a significant problem. Appropriate
      and timely initiatives are needed to prevent and curb drug use among medical
      students.

PMID- 17454018
TI  - The gendered context of initiation to injecting drug use: evidence for women as
      active initiates.
AB  - This paper explores differences between women's and men's first experience of
      injecting in relation to socio-demographic context, drug use, and the role of
      others. We collected cross-sectional retrospective data from 334 recently
      initiated (<or=5 years) injecting drug users in New South Wales and Queensland,
      Australia using a structured questionnaire in face-to-face interviews. Logistic
      regression was used to estimate crude and adjusted odds ratios (OR). Findings
      from the adjusted analysis show that women had a shorter duration of illicit drug
      use prior to initiation (adjusted OR 0.84, 95%CI: 0.74 - 0.94), and were more
      likely to have their romantic-sexual partner facilitate the initiation by paying
      for the drugs (adjusted OR 4.64, 95%CI: 1.21 - 17.73). Women also reported a
      greater likelihood of being initiated in groups of other women (adjusted OR 2.87,
      95%CI: 1.24 - 6.67), suggesting that some women play an active role in their
      initiation experience rather than relying on, or being lead by, a romantic-sexual
      partner. These findings demonstrate the crucial role that romantic-sexual
      partners play in women's initiation experience, but also provide evidence for the
      way that women can be active participants in their own initiation and in
      initiating other women.

PMID- 17454019
TI  - Binge drinking and its detection among middle-aged men using AUDIT, AUDIT-C and
      AUDIT-3.
AB  - Binge (heavy episodic) drinking is common, but there is little knowledge on how
      this drinking pattern could be detected. This study compares three structured
      questionnaires among binge drinking middle-aged men. All 45-year-old men in the
      city of Tampere, Finland, were asked to fill in the Alcohol Use Disorders
      Identification Test (AUDIT). Based on the interview on their drinking the men
      were divided into non-binging moderate drinkers (n = 352), binging moderate
      drinkers (n = 130), non-binging heavy drinkers (n = 10) and binging heavy
      drinkers (n = 63). The complete AUDIT, AUDIT-C (first three AUDIT questions
      inquiring quantity-frequency) and AUDIT-3 (the third binging-frequency question
      of AUDIT) in detecting binge drinking were compared. The complete AUDIT was
      effective in detecting binge drinkers by a cut-off score of >or=8 or >or=7. The
      optimal cut-off score for AUDIT-C was >or= 6 and that for AUDIT-3 >or=2. The area
      under the curve (AUC) among all risky drinkers (binging moderate and binging
      heavy and non-binging heavy drinkers) for AUDIT was 0.824 (95% CI 0.789 - 0.859),
      for AUDIT-C 0.829 (95% CI 0.795 - 0.864) and for AUDIT-3 0.779 (0.739 - 0.818).
      The complete AUDIT and its short versions are applicable in populations where
      binging is the dominant drinking pattern, but the cut-off scores should be
      tailored to individual cultures.

PMID- 17454020
TI  - Screening for drugs in oral fluid: illicit drug use and drug driving in a sample
      of Queensland motorists.
AB  - Police Services in a number of Australian states have indicated random roadside
      drug testing will be implemented to target drug driving. This paper outlines
      research conducted to provide an estimate of the prevalence of drug driving in a
      sample of Queensland drivers. Oral fluid samples were collected from 781 drivers
      who volunteered to participate at Random Breath Testing (RBT) sites in a large
      Queensland regional area. Illicit substances tested for included cannabis (delta
      9 tetrahydrocannibinol [THC]), amphetamine type substances, heroin and cocaine.
      Drivers also completed a self-report questionnaire regarding their drug-related
      driving behaviour. Samples that were drug-positive at initial screening were sent
      to a government laboratory for confirmation. Oral fluid samples from 27
      participants (3.5%) were confirmed positive for at least one illicit substance.
      The most common drugs detected in oral fluid were cannabis (delta 9 THC) (n = 13)
      followed by amphetamine type substances (n = 11). A key finding was that cannabis
      was also confirmed as the most common self-reported drug combined with driving
      and that individuals who tested positive to any drug through oral fluid analysis
      were also more likely to report the highest frequency of drug driving.
      Furthermore, a comparison between drug vs drink driving detection rates for the
      study period revealed a higher detection rate for drug driving (3.5%) vs drink
      driving (0.8%). This research provides evidence that drug driving is relatively
      prevalent on Queensland Roads. The paper will further outline the study findings
      and present possible directions for future drug driving research.

PMID- 17454021
TI  - The relationship between non-acute adolescent cannabis use and cognition.
AB  - Research indicates that cannabis continues to be a popular illegal drug
      internationally. Furthermore, adolescent rates of use appear to be significant.
      Whilst the non-acute effect of cannabis use on adult cognition has been
      extensively researched, there has been less examination of adolescents. This
      study aimed to investigate the non-acute relationship between cannabis and
      cognitive function in a sample of adolescents with a continuum of cannabis use,
      taking into account additional predictor variables (psychiatric functioning,
      general functioning, demographics and other drug use). Seventy adolescents were
      recruited from clinical and community sources as well as through newspaper
      advertisements. After 12 hours abstinence from cannabis, adolescents completed a
      two-hour interview covering: demographics; alcohol and drug use history; drug use
      in the past 28 days; depression; further psychiatric functioning (including ADHD
      and Conduct Disorder); and cognitive functioning as measured by computerised
      tasks (CANTAB) and traditional pen and paper tests. Adolescents who were regular
      cannabis users (more than once a week) had a significantly poorer performance on
      four measures of cognitive function reflecting attention, spatial working memory
      and learning. Cannabis use remained an independent predictor of performance on
      the working memory and strategy measures after additional predictor variables
      were included in a multivariate regression analysis. The results suggest that
      aspects of adolescent cognitive function are independently related to the
      frequency of cannabis use beyond acute intoxication.

PMID- 17454022
TI  - An epidemiological investigation into an outbreak of rash illness among methadone
      maintenance clients in Australia.
AB  - In late 2004, NSW Health received several reports of a serious desquamating rash
      among clients of the methadone program. We sought to identify the extent and
      likely cause of this outbreak. We initiated active surveillance for cases
      throughout Australia, a survey of dosing points in NSW, and a case control study
      of clients receiving methadone syrup (MS) at two clinics. Between October 2004
      and March 2005, 388 cases were identified, largely in NSW. The dosing point
      survey found almost all cases were clients prescribed MS (attack rate 4.5%). In
      multivariate analysis of data from dosing points that dispensed MS, use of take
      away doses or location of the dosing point in greater western Sydney were
      associated with illness. In the case control study, MS injection, use of street
      MS, high doses of MS, frequent takeaway doses, or use of benzodiazepines were
      associated with illness. Testing found no abnormality in associated batches of
      MS. Batches of MS temporally associated with the outbreak were quarantined from
      use and the outbreak subsided. While a direct causal link could not be
      established, available evidence suggests that a contaminant may have caused the
      outbreak. Epidemiological analyses are important for assessing concerns about
      product safety following marketing approval.

PMID- 17454023
TI  - Gender and risk factors for initiation into injection drug use.

PMID- 17454024
TI  - Legal piperazine-containing party pills--a new trend in substance misuse.
AB  - In this Harm Reduction Digest Sheridan, Butler, Wilkins and Russell address the
      emergent phenomenon of so-called 'legal party pills' which have become a
      significant drug issue in New Zealand and elsewhere. Although banned in a number
      of countries, they are currently legally available in New Zealand where they are
      marketed as 'safe' alternatives' to 'illicit' drugs often used in the dance scene
      such as MDMA and amphetamines. The authors describe the availability and use of
      these substances in New Zealand, summarize what is known about their effects, and
      speculate on harm reduction interventions and mechanisms of control and their
      possible sequelae. The paper provides a timely account of an emerging drug issue
      of relevance to harm reduction internationally.

PMID- 17454026
TI  - Reactivation of immobilized acetylcholinesterase-tabun complex by methoxime and
      its homologues.
AB  - Using an immobilized acetylcholinesterase-tabun enzyme-inhibitor complex, the
      reactivation efficacy of a homologous series of bispyridinium reactivators with
      increasing length of the alkylene chain between the pyridinium rings has been
      studied. The number of the alkylene groups in the chain ranged from one to six.
      N,N'-Monomethylenebis(4-pyridiniumaldoxime) dibromide (MMB-4) and N,N'
      trimethylenebis(4-pyridiniumaldoxime) dibromide (TMB-4) are the most efficient
      reactivators of the series.

PMID- 17454027
TI  - A search for the plant ingredients that protect cells from air pollutants and
      benz[a]pyrene phototoxicity.
AB  - A diversity of antioxidants and plant ingredients were examined for their
      protective effect in cultured Balb/c 3T3 cells against ultraviolet A (UVA)
      induced cytotoxicities of extracted air pollutants and benz[a]pyrene (B[a]P) in
      an effort to find effective protectors against the phototoxicity of air
      pollutants and B[a]P. As has been observed for B[a]P phototoxicity, air
      pollutants themselves and those previously exposed to UVA light in the absence of
      cells exhibited faintly weak cytotoxicity, but the toxicity was markedly elevated
      when they were exposed to UVA light concomitantly with cells. The B[a]P
      phototoxicity was not eliminated by well-known antioxidants but was markedly
      diminished by diversity of plant ingredients. Among the plant ingredients tested
      in the current study, morin, naringin, and quercetin were found to be desirable
      protectors against B[a]P phototoxicity.

PMID- 17454028
TI  - A comparison of the potency of newly developed oximes (K074, K075) and currently
      available oximes (obidoxime, HI-6) to counteract soman-induced neurotoxicity in
      rats.
AB  - The neuroprotective effects of newly developed oximes (K074, K075) and currently
      available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned
      with soman were studied. The soman-induced neurotoxicity was monitored using a
      functional observational battery at 24 h and 7 days after soman challenge. The
      results indicate that the oxime HI-6 combined with atropine seems to be an
      effective antidote for a decrease in soman-induced neurotoxicity, whereas the
      ability of both newly developed oximes (K074, K075) as well as obidoxime to
      counteract soman-induced acute neurotoxicity is negligible. Due to the absence of
      their neuroprotective potency, both newly developed oximes are not suitable
      oximes for antidotal treatment after exposure to soman. The oxime HI-6 is still
      the best acetylcholinesterase reactivator for the antidotal treatment of acute
      poisonings with soman.

PMID- 17454029
TI  - Cytogenetic evaluation of paracetamol effects in human lymphocytes culture.
AB  - Paracetamol is a common analgesic and antipyretic drug. It has been recognized as
      one of the most ordinary medications taken in overdoses. We examined the possible
      genotoxic effects of high paracetamol concentrations expected to occur after
      overdose. Paracetamol was added to the cultures at the beginning of the
      cultivation period. Separate cultures for three tested concentrations of
      paracetamol (50 microg/mL, 100 microg/mL, and 200 microg/mL) were set. Effects of
      paracetamol were evaluated by micronucleus cytokinesis-block assay, chromosome
      aberration analysis, and nuclear division index. Results demonstrate that
      paracetamol concentration of 200 microg/mL expresses certain genotoxic effects in
      human peripheral blood lymphocytes.

PMID- 17454030
TI  - Review of the toxicology of three alkyl diamines.
AB  - Three alkyl diamines, which are by-products formed and separated during the
      production of hexamethylene diamine, have been tested, mostly for their acute
      toxicity. This paper reviews methodologies used and the results obtained from
      these three chemicals. All three tested [2-methyl-1,5-pentanediamine (2-MP), 1,3
      diaminopentane (DAMP), and 1,2-cyclohexanediamine (DCH)] were 95% pure and were
      supplied by the DuPont Company. The acute toxicity of all three chemicals is
      relatively low with acute oral lethal levels in the rat ranging from 1000 to 2300
      mg/kg. Single 4-h inhalation exposures show similarly low toxicity with lethality
      produced in the rat at concentrations ranging from 2.9 to 4.3 mg/L. These
      diamines are severe skin irritants in both the rabbit and the guinea pig and are
      also severe eye irritants (studied only in 2-MP). Dermal sensitization was seen
      in the guinea pig with DAMP and DCH but not with 2-MP. The irritant dose of these
      materials was shown in repeated exposure inhalation studies when 2-MP and DCH
      produced irritation in the upper respiratory tract (point of contact) with some
      lower lung involvement but no significant systemic effects. 2-MP when fed to rats
      produced a slight body weight effect at dose equivalents of 800 mg/kg with no
      other parameters affected. All three materials were inactive in Salmonella, and 2
      MP did not produce chromosomal aberrations in cultured human lymphocytes. The
      main effects of this series of diamines appear related to their irritant
      properties, and attention needs to be paid to their delayed hypersensitivity
      potential.

PMID- 17454031
TI  - Efficacy of rifabutin-loaded microspheres for treatment of Mycobacterium avium
      infected macrophages and mice.
AB  - Two poly(DL-lactide-co-glycolide) microsphere formulations (A, 10% wt/wt, and B,
      23% wt/wt, 1-10 microns) were evaluated for intracellular delivery of rifabutin
      using the J774 murine and Mono Mac 6 (MM6) human monocytic cell lines. Within 7
      days, formulation A released 100% in both cell lines and B released 53 and 67% in
      the J774 and MM6, respectively. Intracellular release of rifabutin with both
      formulations caused significant reduction of intracellularly replicating
      Mycobacterium avium (MAC). In MAC-infected beige mice, formulation B (50 mg,
      intraperitoneal days 0 and 7) completely eliminated infection by 21 days (p <
      0.001), similar to a rifabutin daily oral regimen.

PMID- 17454032
TI  - Silica-polyethylene glycol matrix synthesis by sol-gel method and evaluation for
      diclofenac diethyloammonium release.
AB  - Modified silica-polyethylene glycol xerogels were prepared by the sol-gel method
      to explore the possibilities of using these polymers as drug delivery systems.
      The synthesis was performed at room temperature and under atmospheric pressure
      using tetraethylorthosilicate (TEOS) as a precursor, low-molecular polyethylene
      glycol (600) as a modifier, and acetic acid as a catalyst. The composition in a
      mole ratio of the initial sols corresponds to TEOS:H(2)O:EtOH:CH(3)COOH:PEG =
      1:4:6:0.005:0.147. Diclofenac diethyloammonium was used as a model drug and
      encapsulated in predoping sol-gel process. After 5 days of gelation time of
      matrices at room temperature two different forms of xerogels were obtained:
      monolithic form of pellet and cracked, irregular-shaped of particles. The rate of
      release from the both forms of xerogels was controlled by the rate of diffusion
      of the drug through the pores. The dissolution testing for the loaded irregular
      shaped xerogels showed an initial burst release followed by sustained release.
      The degradation of the PEG/silica xerogels followed a zero-order kinetics.

PMID- 17454033
TI  - W/O/W multiple emulsions containing nitroimidazole derivates for vaginal
      delivery.
AB  - The aim of our study was to formulate a stable multiple emulsions containing two
      nitroimidazole derivates, metronidazole (MT) and ornidazole (OR), for vaginal
      therapy. MT and OR were located internal and external phases of multiple
      emulsion, respectively, and the in vitro release studies were realized in
      phosphate (pH 7) and lactate buffer (pH 4.5) solutions to investigate better the
      effect of pH and location of active substance on the release. The imaging studies
      were realized in rabbits following labeling MT and OR with Technethium-99m
      ((99m)Tc) to evaluate the in vivo absorption characteristics. The percentage of
      MT and OR released from the multiple emulsions in alkaline media were 3.2- and
      2.8-fold greater than that observed in acidic media, respectively, when they were
      introduced in the internal phase of the multiple emulsions. The absorption rate
      of MT from vaginal epithelium was faster than OR. We observed that especially in
      alkaline medium a high release was found that was convenient for the vaginal
      infections seen in the alkaline pH. We concluded that W/O/W multiple emulsions
      were locally effective in vagina and they could be introduced as a new drug
      carrier system for vaginal delivery.

PMID- 17454034
TI  - New pH-sensitive glycopolymers for colon-specific drug delivery.
AB  - pH-sensitive hydrogels are suitable candidates for oral delivery of therapeutic
      peptides, proteins, and drugs, due to their ability to respond to environmental
      pH changes. New pH-sensitive glycopolymers have been developed by free-radical
      polymerization of methacrylic acid and 6-acryloyl-glucose-1, 2, 3, 4
      tetraacetate, using 1, 6-hexandiol diacrylate and 1, 6-hexandiol propoxylate
      diacrylate as cross-linking agents. The hydrogels were characterized by
      differential scanning calorimetry and FTIR. Equilibrium swelling studies were
      carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF,
      respectively). A model drug, olsalazine [3, 3'-azobis (6-hydroxy benzoic acid)]
      as an azo derivative of 5-aminosalicylic acid, was entrapped in these gels and
      the in vitro release profiles were established separately in both enzyme-free SGF
      and SIF. The drug-release profiles indicated that the amount of drug released
      depended on the degree of swelling. The hydrogels containing polar propoxylate
      groups were hydrolyzed rather easily.

PMID- 17454035
TI  - Polyelectrolyte complexes of Eudragit l30 d-55 and gelatin: antinociceptive
      activity of entrapped piroxicam.
AB  - The electrostatic interaction between oppositely charged polyelectrolytes leads
      to the formation of polyelectrolyte complexes, which are of considerable interest
      because of their potential applications as both drug carriers or surface
      modifying agents. In this study, in vitro and in vivo studies were carried out on
      polyelectolyte complexes formulated with Eudragit L30 D-55 and gelatin. The
      complexes of Eudragit L30 D-55 and gelatin were formulated by nonstoichiometric
      method. The polyelectrolyte complexes formulated were then granulated and
      evaluated by percentage yield, particle size, and swelling behavior. The
      pharmacodynamic effects of piroxicam entrapped in the complexes were determined
      using healthy rats. Results showed that gelatin and Eudragit L30 D-55 formed
      polyelectrolyte complexes that prolonged the antinociceptive effects of piroxicam
      in experimental rats. The performance of the polyelectrolyte complexes could be
      stated in the following descending rank order: 1:1 > 2:1 > 1:2 ratios of Eudragit
      L30 D-55 and gelatin. Nonstoichiometric interactions of gelatin and Eudragit L30
      D-55 could yield matrices with adequate characteristics for the formulation of
      sustained release systems of drugs.

PMID- 17454036
TI  - In vitro and in vivo studies on HPMC-K-100 M matrices containing naproxen sodium.
AB  - Controlled release (CR) matrix tablets of naproxen sodium were prepared by wet
      granulation using hydroxypropyl methyl cellulose (HPMC-K-100 CR) as the
      hydrophilic rate controlling polymer. The effect of the concentration of the
      polymer and different fillers on the in vitro drug release rate was studied. The
      studies indicated that the drug release can be modulated by varying the
      concentration of the polymer and the fillers. An optimized formulation subjected
      to accelerated stability studies for 3 months revealed that the developed CR
      tablets are stable. A complete cross-over bioavailability study of the optimized
      formulation of the developed CR tablets and marketed immediate release tablets
      was performed in 6 healthy male volunteers. The extent of absorption of drug from
      the CR tablets was significantly higher than that for the marketed naproxen
      sodium tablet due to lower elimination rate and longer half-life.

PMID- 17454037
TI  - Cellular association and cytotoxicity of doxorubicin-loaded immunoliposomes
      targeted via Fab' fragments of an anti-CD74 antibody.
AB  - The purpose of our research was to evaluate in vitro therapeutic efficacy of
      doxorubicin (DXR)-loaded immunoliposomes with Fab' fragments of the anti-CD74
      antibody LL1 attached to the surface. LL1 is well suited for targeting purposes
      because it is internalized very fast by B-lymphoma cells. However, at in vivo
      application whole antibodies show fast clearance in circulation. Taking this fact
      into consideration, this study was initiated to elucidate the prospects of using
      Fab' fragments of LL1 in stead of the whole antibody for future targeting in vivo
      of DXR-loaded liposomes. The Fab' fragments were covalently attached to the
      surface of sterically stabilized liposomes by use of a PEG-based
      heterobifunctinal coupling agent. LL1 Fab' conjugated sterically stabilized DXR
      liposomes showed approximately six times faster accumulation of the drug in Raji
      human B-lymphoma cells than nontargeted liposomes. In vitro cytotoxicity,
      quantitated by a tetrazolium assay, against Raji cells gave IC(50) values of
      0.13, 0.45, and 0.11 microM for DXR-loaded immunoliposomes, DXR-loaded liposomes
      and free drug, respectively. The results from this study suggest that DXR-loaded
      immunoliposomes targeted with Fab' fragments from the anti-CD74 antibody LL1
      could be a useful system for future in vivo experiments.

PMID- 17454038
TI  - Preparation and characterization of a novel nonviral gene transfer system:
      procationic-liposome-protamine-DNA complexes.
AB  - Procationic-liposome-protamine-DNA (PLPD) vector, a novel nonviral gene delivery
      system, that may further adsorb transferrin (Tf) at its surface via electrostatic
      interactions to form Tf-PLPD, was prepared from soybean phosphatidylcholine (PC),
      cholesterol (Chol), and a kind of cholesterol derivative, CHETA(cholest-5-en-3
      ol(3beta)-[2-[[4-[(carboxymethyl)dithio]-1-iminobutyl] amino] ethyl] carba- mate)
      containing disulfide bond by film dispersion-filteration method. Central
      composite design was used to optimize the formulation. The presence of serum did
      not affect the transfection activity of PLPD or Tf-PLPD and the cell viability
      was not affected significantly when the cells were incubated with the complexes
      for 4 hr at 37 degrees C. Compared with one kind of cationic liposomes(liposome
      protamine-DNA), the PLPD had much less cytotoxicity to three hepar cell
      lines(including HepG2, SMMC7721, and Chang's normal heptocyte). The procationic
      lipoplex described here, combining the condensing effect of protamine and the
      targeting capability of Tf, was a perspective nonviral vector for gene delivery
      system.

PMID- 17454041
TI  - Preparation and in vitro/in vivo evaluation of gliclazide loaded Eudragit
      nanoparticles as a sustained release carriers.
AB  - The aim of this study was to formulate and optimize gliclazide-loaded Eudragit
      nanoparticles (Eudragit L100 and Eudragit RS) as a sustained release carrier with
      enhanced efficacy. Eudragit L 100 nanoparticles (ELNP) were prepared by
      controlled precipitation method whereas Eudragit RSPO nanoparticles (ERSNP) were
      prepared by solvent evaporation method. The influence of various formulation
      factors (stirring speed, drug:polymer ratio, homogenization, and addition of
      surfactants) on particle size, drug loading, and encapsulation efficiency were
      investigated. The developed Eudragit nanoparticles (L100 and RS) showed high drug
      loading and encapsulation efficiencies with nanosize. Mean particle size altered
      by changing the drug:polymer ratio and stirring speed. Addition of surfactants
      showed a promise to increase drug loading, encapsulation efficiency, and
      decreased particle size of ELNP as well as ERSNP. Dissolution study revealed
      sustained release of gliclazide from Eudragit L100 as well as Eudragit RSPO NP.
      SEM study revealed spherical morphology of the developed Eudragit (L100 and RS)
      NP. FT-IR and DSC studies showed no interaction of gliclazide with polymers.
      Stability studies revealed that the gliclazide-loaded nanoparticles were stable
      at the end of 6 months. Developed Eudragit NPs revealed a decreased t(min)
      (ELNP), and enhanced bioavailability and sustained activity (ELNP and ERSNP) and
      hence superior activity as compared to plain gliclazide in streptozotocin induced
      diabetic rat model and glucose-loaded diabetic rat model. The developed Eudragit
      (L100 and RSPO) NP could reduce dose frequency, decrease side effects, and
      improve patient compliance.

PMID- 17454042
TI  - In vitro and in vivo performance of a multiparticulate pulsatile drug delivery
      system.
AB  - The objective of this study was to investigate the in vitro and in vivo drug
      release performance of a rupturable multiparticulate pulsatile system, coated
      with aqueous polymer dispersion Aquacoat ECD. Acetaminophen was used as a model
      drug, because in vivo performance can be monitored by measuring its concentration
      in saliva. Drug release was typical pulsatile, characterized by lag time,
      followed by fast drug release. Increasing the coating level of outer membrane lag
      time was clearly delayed. In vitro the lag time in 0.1 N HCl was longer, compared
      to phosphate buffer pH 7.4 because of ionisable ingredients present in the
      formulation (crosscarmelose sodium and sodium dodecyl sulphate). In vitro release
      was also longer in medium with higher ion concentration (0.9% NaCl solution
      compared to purified water); but independent of paddle rotation speed (50 vs.100
      rpm). Macroscopically observation of the pellets during release experiment
      confirms that the rupturing of outer membrane was the main trigger for the onset
      of release. At the end of release outer membrane of all pellets was destructed
      and the content completely released. However, pellets with higher coating level
      and correspondingly longer lag time showed decreased bioavailability of
      acetaminophen. This phenomenon was described previously and explained by
      decreased liquid flow in the lower part of intestine. This disadvantage can be
      considered as a limitation for drugs (like acetaminophen) with high dose and
      moderate solubility; however, it should not diminish performance of the
      investigated system in principle.

PMID- 17454043
TI  - Influence of metronidazole particle properties on granules prepared in a high
      shear mixer-granulator.
AB  - Metronidazole is a good example of high-dose drug substance with poor granulating
      and tableting properties. Tablets are generally produced by liquid granulation;
      however, the technological process failure is quite frequent. In order to verify
      how the metronidazole particle characteristics can influence granule properties,
      three metronidazole batches differing for crystal habit, mean particle size, BET
      surface area and wettability were selected, primarily designed according to their
      different elongation ratio: needle-shaped, stick-shaped, and isodimensional. In
      the presence of lactose monohydrate and pregelatinized maize starch, respectively
      as diluent and binder, they were included in a formula for wet granulation in a
      high-shear mixer-granulator. In order to render the process comparable as far as
      possible, all parameters and experimental conditions were maintained constant.
      Four granule batches were obtained: granules from placebo (G-placebo), granules
      from needle-shaped crystals (G-needle-shaped), granules from stick-shaped
      crystals (G-stick-shaped), and granules from isodimensional crystals (G
      isodimensional). Different granule properties were considered, in particular
      concerning porosity, friability, loss on drying (LOD), and flowability. In order
      to study their tabletability and compressibility, the different granules obtained
      were then compressed in a rotary press. The best tabletability was obtained with
      the isodimensional batch, while the poorest was exhibited by the stick-shaped
      one. Differences in tabletability are in good accordance with compressibility
      results: to a better tabletability corresponds an important granule ability to
      undergo a volume reduction as a result of an applied pressure. In particular, it
      was proposed that the greatest compressibility of the G-isodimensional must be
      related to the greatest granule porosity percentage.

PMID- 17454044
TI  - In vitro antimicrobial effect of encapsulated vancomycin on internalized
      Staphylococcus aureus within endothelial cells.
AB  - Vancomycin (VCN) is a glycopeptide antibiotic that is effective in the treatment
      of gram-positive bacterial infections, but mainly reserved for methicilin
      resistant Staphylococcus aureus. It is, however, ineffective against
      intracellular bacteria and hence a particulate form of VCN would be required.
      Bovine serum albumin (BSA) microspheres of VCN with a mean particle size of 5 +/-
      1.6 microm were used. Human microvascular endothelial cells internalized both S.
      aureus and VCN microspheres in a time and concentration-dependent manner,
      however, the uptake was inhibited by cytochalasin D. Action of VCN on S. aureus
      in the intracellular microenvironment decreased the bacterial load considerably.

PMID- 17454045
TI  - Study of the effect of stirring on foam formation from various aqueous acrylic
      dispersions.
AB  - Acrylic polymers in aqueous dispersions are very often used to prepare coating
      suspensions which contain insoluble particles. The mixing of the pigment
      suspension and the polymer dispersion is a very important step in the preparation
      of the liquid. The stirring can cause precipitation of the polymer and foam
      formation. Foam formation from different Eudragit dispersions was evaluated in
      this study. A high-speed mixer was applied and the foam and liquid phases formed
      were separated. The changes in concentration of the polymer in the two phases
      were studied by FT-IR with a horizontal attenuated total reflection (HATR)
      accessory. The presence of shape-holding foam can be detected at very different
      rates of stirring. The most intensive foam formation was detected for Eudragit FS
      30 D. The Eudragit RL 30 D dispersion was the least sensitive to high-speed
      mixing. The relative content of the polymer in the foam was higher than that in
      the liquid. This is indicated by the accumulation of surface-active agent on the
      surface of the bubbles formed in the foam. This phenomenon differed considerably
      for the various dispersions. An exact knowledge of the foam formation from
      aqueous acrylic dispersions is very important in order to determine the
      parameters of mixing and the quantity of antifoaming agent.

PMID- 17454046
TI  - Formulation and characterization of formaldehyde cross-linked degradable starch
      microspheres containing terbutaline sulfate.
AB  - Preparation of starch microspheres using epichlorohydrin is a time consuming
      method and requires around 18 hr for cross-linking reaction. To reduce reaction
      time, terbutaline sulfate (TBS) loaded degradable starch microspheres (DSM) were
      prepared using formaldehyde as the cross-linking agent. All microspheres were
      spherical in shape and had a porous, rough surface with a mean particle size of
      18-24 microm. Whatever the cross-linking time, it was seen that the release of
      the TBS was not complete during the release experiments. The influence of enzyme
      on the degradation of microspheres was moderate. Following intravenous
      administration, initial uptake of microspheres by the lung was higher than those
      of other organs.

PMID- 17454047
TI  - Particle size coarsening induced by valve silicone in a metered dose inhaler.
AB  - The objective of this study was to evaluate the effect of valve silicone on the
      delivered particle size distribution of a suspension metered dose inhaler (MDI).
      Valves were manufactured with distinct levels of silicone, which could be
      differentiated with Fourier transform infrared spectroscopy (FT-IR). The amount
      of silicone in the valve was proportional to the amount of silicone that entered
      the formulation and the subsequent decrease in fine particle fraction (FPF) of
      the active pharmaceutical ingredient (API) measured by Andersen cascade
      impaction. The effect of silicone content was not linear as even small amounts of
      silicone made a significant contribution to particle size coarsening. This
      coarsening was also a function of storage time and temperature. Accelerated
      stability conditions greatly increased coarsening kinetics as 1 month at 40
      degrees C and 75% RH induced significantly more coarsening than 12 months at room
      temperature. Field emission scanning electron micrograph images suggest that the
      primary mechanism of particle size change may be aggregation as particle clusters
      were seen. This study indicates that silicone can be a critical process parameter
      for particle size distribution of a suspension MDI product. Thus, the amount of
      silicone in the valves needs to be minimized and controlled.

PMID- 17454048
TI  - Investigation and physicochemical characterization of clarithromycin-citric acid
      cyclodextrins ternary complexes.
AB  - The purpose of this study was to investigate the effect of citric acid (CA) on
      the complexation of clarithromycin (CLM) with beta-cyclodextrin (betaCD) in
      aqueous solutions and in the solid state. A phase solubility study revealed a
      positive effect of CA on the drug solubility. A B(s)-type solubility with an
      apparent stability constant (K(c)) of 102.4 M(-1) was obtained for CLM in betaCD
      solution and 161.2 M(-1) for CLM in 6 mM betaCD solution. Solid ternary complexes
      were prepared by coevaporation and lyophilization. CLM-betaCD-CA interactions
      were studied in the solid state by differential scanning calorimetry (DSC),
      infrared spectroscopy, scanning electron microscopy and X-ray diffractometry. A
      part of the guest molecule was located in the betaCD host cavity. The results
      obtained suggest that the lyophilization method yields a higher degree of
      amorphous entity than coevaporation.

PMID- 17454049
TI  - A validated stability indicating high performance reverse phase liquid
      chromatographic method for the determination of cilostazol in bulk drug
      substance.
AB  - A simple, rapid and accurate reverse phase high-performance liquid
      chromatographic (RP-HPLC) method was developed for the quantitative determination
      of cilostazol. The developed method is also applicable for the related substance
      determination in bulk drugs. The chromatographic separation was achieved on
      reversed-phase C-18 column. Eluents were monitored on photo-diode array detector
      at a wavelength of 210 nm using a mixture (50:50) of water and acetonitrile.
      Solution concentrations were quantified by external calibration. In the developed
      HPLC method, resolution between cilostazol and its potential impurities, namely
      Imp-A, Imp-B, and Imp-C were found greater than two. The drug was subjected to
      stress condition of hydrolysis, oxidation, photolysis and thermal degradation.
      Considerable degradation was found to occur in alkaline medium stress condition.
      The developed RP-HPLC method was validated with respect to linearity, accuracy,
      precision, stability of analytical solutions, and robustness.

PMID- 17454050
TI  - In vitro evaluation and targeting of E. coli internalized by endothelial cells
      using albumin microspheres loaded with gentamicin.
AB  - The purpose of this study was to evaluate the use of microencapsulated form of
      gentamicin and the traditional solution form for its intracellular bactericidal
      effect. Bovine serumalbumin (BSA) microspheres loaded with gentamicin were
      prepared by using Mini Spray Dryer. Human microvascular endothelial cells (HMECs)
      were exposed to increasing concentrations of Escherichia coli leading to
      internalization of E. coli. The internalized bacteria were targeted using either
      the microencapsulated or the solution form of gentamicin. The treatment groups
      using gentamicin solution form and microsphere form showed almost 46% and 86%
      inhibition in the growth of the internalized bacteria, respectively.

PMID- 17454051
TI  - Formulation development and stability studies of aqueous metronidazole benzoate
      suspensions containing various suspending agents.
AB  - Metronidazole is a synthetic antibacterial and antiprotozoan agent.
      Crystallization occurs in aqueous metronidazole benzoate suspensions caused by an
      anhydrate to monohydrate conversion. This study aimed to develop an aqueous
      metronidazole benzoate suspension that does not exhibit this hydration and the
      accompanying crystal growth. Four suspending agent systems were evaluated.
      Xanthan gum and Avicel RC-591 (a combination of microcrystalline cellulose and
      carboxymethylcellulose sodium) were found to be the suspending agents that
      resulted in optimal formulation properties. Monohydrate formation did not occur
      in product containing Avicel RC-591, indicating that suspending agents may exert
      a positive effect on metronidazole benzoate suspension stability.

PMID- 17454052
TI  - Evaluation of in vitro enzymatic degradation of various thiomers and cross-linked
      thiomers.
AB  - The aim of this study was to examine the biodegradability of thiomers and cross
      linked thiomers in comparison with unmodified polymers. Disulfide-cross-linked
      conjugates were prepared by air oxidation at room temperature. Thiomers were
      investigated by viscosity measurements and spectrophotometric assays. The
      influence of different factors on the hydrolysis rate, such as the degree of
      modification of thiomers, structure of the conjugates, pH value of the reaction
      medium, and the impact of the process of cross-linking were evaluated. Due to the
      modification, thiolated chitosans degraded 12.9-24.7% less than unmodified
      chitosan in the framework of viscosity measurements. In addition, the hydrolysis
      degree of thiolated alginates and modified carboxymethylcelluloses was 25.6-32.4%
      and 18.4-27.0% lower, respectively, in comparison to the corresponding unmodified
      polymers. Conjugates with higher coupling rate of thiol groups were degraded even
      more slowly. Moreover, the cross-linking process via disulfide bonds additionally
      reduced the rate of thiomer degradation. The range of degradation rates achieved
      in vitro could be modified by alterations of the contents of thiol and disulfide
      groups, as well as by suitable design of the polymer structure and ligands used.
      These results represent helpful basic information for the development of
      mucoadhesive drug delivery systems, implantable delivery systems and tissue
      engineering constructs.

PMID- 17454054
TI  - Cyclosporine A: a review of current oral and intravenous delivery systems.
AB  - As early as 1978, the immunosuppressive effect of cyclosporine A (CsA), a
      metabolite of the fungus Tolypocladium inflatum (Borel, 1989), was reported to be
      effective in inhibiting organ rejection in patients receiving kidney transplants
      from mismatched cadaver donors (Calne et al., 1978) and in the treatment of graft
      versus-host disease in patients with acute leukemia following bone marrow
      transplants (Powles et al., 1978). Today, CsA is still indicated to prevent
      rejection following solid organ transplantations, prevent and treat graft-vs-host
      disease following bone marrow transplants, and has also been used in the
      treatment of autoimmune disease such as psoriasis, rheumatoid arthritis, and
      nephrotic syndrome (Canadian Pharmacists Association, 2006). The effectiveness of
      CsA is derived from its ability to specifically and reversibly inhibit
      immunocompetent lymphocytes in the G(0) and G(1) phase of the cell cycle. The T
      helper cells are the main target, but suppression of the T-suppressor cells also
      occurs. The production and release of lymphokines, including interleukin-2 are
      also inhibited (Novartis, 2005a). CsA can be administered intravenously as well
      as orally in the form of a solution or a soft gelatin capsule. The following
      review will focus on the evolution of the emulsion-based oral formulations from
      the first generation as Sandimmune to the second generation Neoral, both products
      of Novartis Pharmaceutical, as well as on the Sandimmune commercial intravenous
      formulation. The potential of alternative delivery systems, including micelles,
      micro- and nanoparticles, and liposomes, will also be discussed.

PMID- 17454055
TI  - The physicochemical characterization and in vitro/in vivo evaluation of natural
      surfactants-based emulsions as vehicles for diclofenac diethylamine.
AB  - Two sugar-based emulsifiers, cetearyl alcohol & cetearyl glycoside and sorbitan
      stearate & sucrose cocoate, known as potential promoters of lamellar liquid
      crystals/gel phases, were investigated in order to formulate an optimal vehicle
      for amphiphilic drug - diclofenac diethylamine (DDA). Physico-chemical
      characterization and study of vehicle's physical stability were performed. Then,
      the in vitro DDA liberation profile, dependent on the mode of drug incorporation
      to the system, and the in vivo, short-term effects of chosen samples on skin
      parameters were examined. Droplets size distribution and rheological behavior
      indicated satisfying physical stability of both types of vehicles. Unexpectedly,
      the manner of DDA incorporation to the system had no significant influence on DDA
      release. In vivo study pointed to emulsion's favorable potential for skin
      hydration and barrier improvement, particularly in cetearyl glycoside-based
      vehicle.

PMID- 17454056
TI  - Quantifying the degree of disorder in micronized salbutamol sulfate using
      moisture sorption analysis.
AB  - Salbutamol sulfate is often micronized for use in dry powder inhalers. Therefore,
      it is of high interest to quantify the amorphous amount. It was investigated
      whether moisture sorption is able to measure the amorphous content of salbutamol
      sulfate. Different mixtures of amorphous and crystalline salbutamol sulfate were
      analyzed by moisture sorption. The amorphous material was obtained by spray
      drying. The measurement results were used to plot a calibration curve, which was
      used to quantify the amorphous amount in micronized salbutamol sulfate.

PMID- 17454057
TI  - Preparation and characterization of quercetin and rutin cyclodextrin inclusion
      complexes.
AB  - The objective of the present study is to prepare and characterize cyclodextrin
      inclusion complexes of quercetin and rutin to improve their aqueous solubility
      and dissolution properties. Inclusion complexes of quercetin and rutin with beta
      cyclodextrin (beta-CD) and hydroxyl propyl-beta-cyclodextrin (HP-beta-CD) were
      prepared by kneading and coevaporation methods. Characterization of inclusion
      complexes was done by phase solubility analysis and was supported by X-ray powder
      diffractometry (XRD), differential scanning calorimetry (DSC), and Fourier
      transform infra red spectroscopy (FT-IR) analysis. Inclusion complexes exhibited
      higher rates of dissolution than the corresponding physical mixtures and pure
      drug. Higher dissolution rates were observed with HP-beta-CD kneaded complexes in
      comparison to the products with beta-CD.

PMID- 17454058
TI  - Development of polysaccharide-based colon targeted drug delivery systems for the
      treatment of amoebiasis.
AB  - The main focus of this study is to develop colon targeted drug delivery systems
      for metronidazole (MTZ). Tablets were prepared using various polysaccharides or
      indigenously developed graft copolymer of methacrylic acid with guar gum (GG) as
      a carrier. Various polysaccharides such as GG, xanthan gum, pectin, carrageenan,
      beta-cyclodextrin (CD) or methacrylic acid-g-guar (MAA-g-GG) gum have been
      selected and evaluated. The prepared tablets were tested in vitro for their
      suitability as colon-specific drug delivery systems. To further improve the colon
      specificity, some selected tablet formulations were enteric coated with Eudragit
      L 100 to give protection in an acidic environment. Drug release studies were
      performed in simulated gastric fluid (SGF) for 2 hr followed by simulated
      intestinal fluid (SIF) at pH 7.4. The dissolution data demonstrate that the rate
      of drug release is dependent upon the nature and concentration of
      polysaccharide/polymer used in the formulations. Uncoated tablets containing
      xanthan gum or mixture of xanthan gum with graft copolymer showed 30-40% drug
      release during the initial 4-5 hr, whereas for tablets containing GG with the
      graft copolymer, it was 70%. After enteric coating, the release was drastically
      reduced to 18-24%. The other polysaccharides were unable to protect drug release
      under similar conditions. Preparations with xanthan gum as a matrix showed the
      time-dependent release behavior. Further, in vitro release was performed in the
      dissolution media with rat caecal contents. Results indicated an enhanced release
      when compared to formulations studied in dissolution media without rat caecal
      contents, because of microbial degradation or polymer solubilization. The nature
      of drug transport was found to be non-Fickian in case of uncoated formulations,
      whereas for the coated formulations, it was found to be super-Case-II.
      Statistical analyses of release data indicated that MTZ release is significantly
      affected by the nature of the polysaccharide used and enteric coating of the
      tablet. Differential scanning calorimetry indicated the presence of crystalline
      nature of drug in the formulations.

PMID- 17454059
TI  - Chitosan formulations for steroid delivery: effect of formulation variables on in
      vitro characteristics.
AB  - Chitosan film formulations for steroid delivery after craniomaxillofacial surgery
      were formulated by using three different types of chitosan with respect to their
      molecular weight as low, medium and high. Film formulations were prepared by
      casting/solvent evaporation technique. In vitro characterization, film thickness,
      equilibrium swelling degree, in vitro release profiles and surface morphologies
      were investigated. For two different types of crosslinkings, the release of
      dexamethasone sodium phosphate (DSP) can be extended as the molecular weight
      increases. As a result, chitosan film formulations should be beneficial for
      steroid delivery for a certain time after craniomaxillofacial surgery.

PMID- 17454060
TI  - Topical delivery of fluconazole: in vitro skin penetration and permeation using
      emulsions as dosage forms.
AB  - We investigated in vitro skin penetration and permeation of fluconazole from
      emulsions containing different penetration enhancers. Fluconazole permeation was
      high (15-65% of the applied dose) across hairless mouse skin and low (8-9%)
      across pig ear skin. Permeation across mice skin from a formulation containing
      propyleneglycol and isopropyl myristate was significantly higher than that
      observed with the paraffin oil and propyleneglycol or Transcutol emulsions. With
      pig skin, the paraffin oil or isopropyl myristate and propyleneglycol emulsions
      showed similar skin permeation and penetration. However, these emulsions provided
      epidermal concentrations higher than the minimal inhibitory concentrations for
      most dermatophytes.

PMID- 17454061
TI  - Water soluble cellulose acetate: a versatile polymer for film coating.
AB  - The objective of this study was to investigate the use of water soluble cellulose
      acetate (WSCA) as a film coating material for tablets. Aspirin (ASA) tablets were
      prepared by direct compression and coated with either WSCA or HPMC (hydroxypropyl
      methylcellulose) dispersions. Coatings of 1-3%, depending on the intended
      application, were applied to the model drug (ASA) tablets employing a side-vented
      coating pan. Free films of WSCA, prepared by cast method, are crystal clear and,
      depending on the viscosity grade, are flexible, strong and durable. WSCA has the
      capability of forming free films without plasticizers and the films dry at room
      temperature. Glass transition temperature, Tg, was determined by differential
      scanning calorimetry. The Tg of WSCA is significantly higher relative to HPMC.
      Inclusion of plasticizer lowers the Tg of WSCA and effective plasticizers were
      PEG 400 and glycerin. Low viscosity WSCA was more soluble in water (25-30%)
      relative to medium viscosity WSCA (10-15%). WSCA solutions exhibited no increase
      in viscosity with an increase in temperature. Samples of coated (WSCA and HPMC)
      tablets and uncoated ASA cores were packaged for stability studies at room and
      elevated temperature storage. Physical stability of ASA tablets coated with 2:1
      LV: MV (low viscosity: medium viscosity) WSCA formulations was better when
      compared to tablets coated with HPMC. Dissolution stability of WSCA coated ASA
      was similar to the physical stability results. After three months at elevated
      temperature (35 and 45 degrees C), the WSCA coated tablets complied with USP
      dissolution requirements for ASA, while the HPMC coated tablets did not. There
      was no difference in moisture (weight) gain of ASA tablets coated with either
      WSCA or HPMC. The WSCA coated tablets were not sticky or tacky, while the HPMC
      coated tablets were tacky and stuck together.

PMID- 17454062
TI  - The impact of trimethyl chitosan on in vitro mucoadhesive properties of pectinate
      beads along different sections of gastrointestinal tract.
AB  - Pectinate (PEC) beads are multiparticulate dosage forms which have been
      extensively investigated for oral drug delivery; however their mucoadhesive
      properties in various sections of GI tract have, not been yet reported. This work
      evaluated the in vitro mucoadhesive properties of PEC bead formulations, on rat
      everted gastrointestinal sections, either with or without trimethyl chitosan
      (TMC), an absorption-enhancing and fairly mucoadhesive derivative of chitosan.
      Reference Carbomer 934P (C934P) granules, as an established mucoadhesive polymer,
      and ethyl cellulose (EC)-coated pellets, as a nonmucoadhesive dosage form, were
      also used for comparison. Water uptake studies were also performed to further
      explain the effect of hydration on mucoadhesive properties. PEC beads showed
      mucoadhesion, which was in some cases comparable to C934P granules, towards the
      gastrointestinal tissues with following ranking: duodenum approximately jejunum
      approximately ileum > cecum > colon > stomach. In the dry state, the beads
      containing TMC were more mucoadhesive, while in the moist state simple PEC beads
      were shown to be more mucoadhesive. Over-hydration of TMC-containing beads may
      account for this observation. The results of this study suggest that in cases
      which prehydration can be avoided, such as when the beads are protected in a site
      specific oral capsule, prior to reaching the target tissue, the incorporation of
      TMC into beads might be useful, as a means of increasing the mucoadhesive
      properties; However, further studies are needed to clarify their in vivo
      feasibility.

PMID- 17454063
TI  - Comparison of the solubility and dissolution rate between gliclazide solid
      complex and its nanospheres.
AB  - The solid complex of gliclazide and beta-cyclodextrin was prepared by
      neutralization method and the precipitation solvent evaporation method was used
      to prepare gliclazide nanospheres. Fourier-transform infrared spectroscopy and
      differential scanning calorimetry were used to examine whether gliclazide solid
      complex and gliclazide nanospheres were successfully formed in this study. The
      dissolution rate of gliclazide from its nanospheres was faster than its solid
      complex and pure drug. The morphology of particles for nanospheres showed no
      crystal character of gliclazide. In summary, the results indicate that
      nanotechnology provides better effects in solubility and dissolution rate of
      gliclazide than neutralization method.

PMID- 17454064
TI  - Ternary complexes of flurbiprofen with HP-beta-CD and ethanolamines
      characterization and transdermal delivery.
AB  - Binary and multicomponent systems complexes prepared with HP-beta-CD and/or with
      monoethanolamine (MEA), diethanolamine (DEA) or triethanolamine (TEA) were
      obtained. The results of solid-state studies indicated the presence of strong
      interactions between the components in the binary and the ternary systems. Drug
      solubility and dissolution rate in water were notably improved by employing the
      HP-beta-CD and the alkanolamines. The combined use of cosolvency and complexation
      with MEA in the presence of HP-beta-CD on the permeation of flurbiprofen through
      the human skin was evaluated. The combination of IPM, PG, and HP-beta-CD yield
      the highest permeation for the flurbiprofen-MEA complex.

PMID- 17454065
TI  - Statistical evaluation of influence of xanthan gum and guar gum blends on
      dipyridamole release from floating matrix tablets.
AB  - The present investigation explored the use of xanthan gum and guar gum for
      development of floating drug delivery system of dipyridamole using factorial
      design approach. The content of polymer blends (X(1)) and ratio of xanthan gum to
      guar gum (X(2)) were selected as independent variables. The diffusion exponent
      (n), release rate constant (k), percentage drug release at 1 hr (Q(1)) and 6 hr
      (Q(6)) were selected as dependent variables. Tablets of all batches had desired
      buoyancy characteristics. Multiple regression analysis with two way ANOVA
      revealed that both the factors had statistically significant influence on the
      response studied (p<0.05). Results of Tukey test showed the relative contribution
      of each level of different factors for the response studied. It was concluded
      that the ratio of xanthan to gaur gum had equal or dominant role as controlling
      factor on kinetics of drug release compared to content of polymer blends.

PMID- 17454066
TI  - Pharmacokinetics and bioequivalence studies of galantamine hydrobromide
      dispersible tablet in healthy male Chinese volunteers.
AB  - A randomized, two-way, crossover study was conducted in 18 healthy male Chinese
      volunteers to compare pharmacokinetics profiles of galantamine hydrobromide
      dispersible tablet with that of conventional tablet. A single oral dose of 10 mg
      galantamine was administrated to each volunteer. Plasma concentrations of
      galantamine were determined by a validated high-performance liquid chromatography
      (HPLC) method with fluorescence detection, which allowed 1 ng/mL to be assayed as
      the lowest quantifiable concentration. From plasma concentrations, AUC(0-->t)
      (the area under the plasma concentration-time curve from time 0 to the last
      sampling time, 32 hr), AUC(0-->infinity) (the area under the plasma concentration
      time curve from time 0 to infinity), t((1/2)) (elimination of half-life of the
      terminal log linear phase), C(max) (maximum plasma drug concentration) and T(max)
      (time to reach C(max)) were evaluated through noncompartmental pharmacokinetic
      analysis. AUC(0-->t) and AUC(0-->infinity) were calculated by the linear-log
      trapezoidal rule method. C(max) and T(max) were obtained directly from the plasma
      concentration-time curve. Analysis of variance was carried out using
      logarithmically transformed AUC(0-->t), AUC(0-->infinity) and C(max). As far as
      AUC(0-->t), AUC(0-->infinity) and C(max) were concerned, there was no
      statistically significant difference between the test and reference formulations.
      Ninety percent confidence intervals (90% CI) for the ratio of AUC(0-->t), AUC(0-
      >infinity) and C(max) values for the test and reference formulations were 100.4
      107.8%, 99.0-107.2% and 87.5-111.3%, respectively. As the 90% CIs of AUC(0-->t),
      AUC(0-->infinity) and C(max) were entirely within 80-125%, two formulations were
      considered bioequivalent.

PMID- 17454067
TI  - Development of a multiple unit pellet formulation for a weakly basic drug.
AB  - SAG/ZK [3-(5-Chloro-2-[2-[(2R)-4-(4-fluorobenzyl)-2-methylpiperazin-1-yl]-2
      oxoethoxy]phenyl)uronium hydrogen sulfate], a potent candidate for the oral
      treatment of inflammatory diseases, demonstrated pH-dependent solubility. Drug
      release from conventional pellet formulations decreased with increasing pH values
      of the dissolution medium. The aim of this study was to overcome this problem and
      to achieve pH-independent drug release. Extended release pellets were prepared by
      extrusion/spheronization followed by film coating with an aqueous
      polyvinylacetate/polyvinylpyrrolidone dispersion. To overcome the problem of pH
      dependent drug release organic acids such as fumaric, tartaric, and adipic acid
      were incorporated into the core pellets. X-ray diffraction studies were done in
      order to investigate potential recrystallization and formation of different salts
      of SAG/ZK. The addition of fumaric acid was found to lower the pH values within
      the core pellets during the release of SAG/ZK in phosphate buffer pH 6.8.
      Therefore, increased release rates at higher pH values were observed thus leading
      to pH-independent drug release. In contrast, drug release remained pH-dependent
      for pellets containing tartaric and adipic acid, which can be explained with the
      lower acidic strength and higher aqueous solubility of these acids. X-ray
      diffraction studies showed no recrystallization and formation of salts of active
      ingredient and organic acid.

PMID- 17454069
TI  - Inside the "pro-ana" community: a covert online participant observation.
AB  - A covert participant observation was conducted into the meanings of interaction
      in the "pro-ana" online community. Specifically, the researchers were interested
      in the kind of psychological support offered by such websites and by the beliefs
      of community members towards eating disorders and the processes of treatment and
      recovery. One of the authors joined a number of pro-ana sites in the guise of a
      plausible persona and experienced a variety of responses from community members,
      some extremely hostile, others very supportive, yet without ever being exposed as
      an interloper. These starkly different responses challenge the notion of a broad
      "pro-ana" philosophy, suggesting that the sites are best understood as local
      cliques offering temporary relief from offline hostility, but it is doubtful
      whether they can be said to possess any therapeutic value beyond the immediate
      online context.

PMID- 17454070
TI  - Treatment responses of inpatient eating disorder women with and without co
      occurring obsessive-compulsive disorder.
AB  - We analyzed the influence of co-occurring obsessive-compulsive disorder (OCD) on
      response to eating disorder (ED) treatment among 2,971 female inpatients. We
      assessed treatment response using Eating Disorder Inventory-2 and DSM-IV ED
      criteria. Multivariate analyses included sociodemographics, illness severity, and
      co-occurring Axis I/II diagnoses. ED inpatients with OCD had greater ED severity
      than those without OCD. However, no differences occurred in short- and
      intermediate-term ED outcomes. Patients with and without OCD evidenced the same
      degree of change in EDI-2 scores admission-to-discharge and discharge-to-one
      year; and 93% of patients both with and without OCD no longer evidenced a DSM-IV
      ED diagnosis one-year post-discharge. Results suggest that with co-occurring OCD
      treated using evidence-based interventions ED inpatients with and without OCD may
      have similar prognoses.

PMID- 17454071
TI  - Causes of adolescent onset anorexia nervosa: patient perspectives.
AB  - This qualitative study describes the perspectives of former anorexia nervosa (AN)
      patients with respect to why they believed they developed AN. Previous patients
      with initial treatment in child and adolescent psychiatric clinics in northern
      Sweden were interviewed 8 and 16 years after initial assessment. The question,
      "What do you think today about the reasons why you got AN?" was asked at both
      interviews. Content analyze was used to categorize the answers. Causes were
      attributed to self, family, and socio-cultural stressors outside of the family.
      Most common were high own demands and perfectionism. At the second follow-up
      there were more answers in the family categories. The results agreed with results
      from risk-factor research.

PMID- 17454072
TI  - Treatment of obesity in the primary care setting: are we there yet?
AB  - Obesity is a significant public health issue in the US constituting an
      independent risk factor for morbidity and mortality as well as complicating the
      management of other medical conditions. Yet, traditionally most physicians
      receive little training in evidence-based obesity interventions. Previous
      literature suggests many physicians believe they do not have effective tools to
      address obesity and/or that obesity management is not within their scope of
      practice. Given the new emphasis from NIH and AAFP urging physicians to
      conceptualize and treat obesity as a chronic medical condition, we examined
      obesity-related knowledge and practices among military and civilian primary care
      physicians. Results were similar across these two physician groups in suggesting
      many physicians still may be ill-prepared to manage obesity in the primary care
      setting. Implications for patient care and future research are discussed.

PMID- 17454073
TI  - Gastric bypass surgery: a survey of primary care physicians.
AB  - Gastric bypass surgery has become an increasingly recognized treatment option for
      individuals suffering from morbid obesity. However, no previous empirical studies
      have examined the beliefs and attitudes of primary care physicians with regard to
      this type of intervention. Using a cross-sectional survey approach, we queried 99
      primary care physicians about their beliefs and attitudes. With the exception of
      queries about insurance coverage, the response patterns evidenced a clear
      majority for most items. For several items, there were some interesting
      inconsistencies, which may suggest physician ambivalence. In the final analysis,
      84% of respondents supported the recommendation of gastric bypass surgery for
      qualifying patients. However, there was a significant gender difference, with
      female physicians being less supportive than male physicians. We discuss the
      implications of these results.

PMID- 17454074
TI  - Effect of a specialist eating disorders service on the knowledge and attitudes of
      local health professionals.
AB  - This study investigated the effect of a specialist eating disorders service on
      the attitudes and knowledge of local healthcare professionals. A questionnaire
      was sent to fully qualified psychiatrists, postgraduate trainees in psychiatry
      and general (internal) medicine, general practitioners (family physicians) and
      dietitians in two comparable cities: Leicester (which had a specialist eating
      disorders service) and Nottingham (which did not). Psychiatrists in training in
      Leicester had a greater knowledge of eating disorders than those in Nottingham.
      There was greater satisfaction with services in Leicester but no difference in
      attitudes. The presence of a local eating disorders service enhances postgraduate
      training and increases knowledge.

PMID- 17454079
TI  - Magnetic field therapy: a review.
AB  - There is increasing interest in using permanent magnets for therapeutic purposes
      encouraged by basic science publications and clinical reports. Magnetotherapy
      provides a non invasive, safe, and easy method to directly treat the site of
      injury, the source of pain and inflammation, and other types of disease. The
      physiological bases for the use of magnetic fields for tissue repair as well as
      physical principles of dosimetry and application of various magnetic fields are
      subjects of this review. Analysis of the magnetic and electromagnetic stimulation
      is followed by a discussion of the advantage of magnetic field stimulation
      compared with electric current and electric field stimulation.

PMID- 17454075
TI  - Targeting students, teachers and parents in a wellness-based prevention program
      in schools.
AB  - This study examines the effectiveness of a wellness-based prevention program on
      elementary and junior high students' body image, personal attitudes, and eating
      behaviors. Group differences in measures of student attitudes and eating
      behaviors are examined to determine the effect of targeting different participant
      combinations (students, parents, and teachers) in 10 groups. For elementary
      schools, student participants consisted of control (no intervention) (n = 36),
      student only (n = 81), student/parent (n = 124), student/parent/teacher (n =
      103), and parent/teacher (n = 149). For junior high schools, student participants
      consisted of control (n = 143), student only (n=215), student/parent (n=65),
      student/parent/teacher (n = 14), and parent/teacher (n = 177). Overall, complete
      data was available for 1,095 students, 114 parents and 92 teachers. Results
      indicate that self-concept and eating attitudes and behaviors were positively
      affected by participation in the program. For example, in elementary schools
      posttest scores on the behavior subscale of the self-concept measure are
      significantly higher for the student/parent/teacher group than for the control
      group. Results indicate that a one-time wellness-based eating disorder prevention
      program with students, which have in the past shown to be minimally effective,
      may be more effective in changing attitudes and behaviors when teachers and
      parents are involved.

PMID- 17454080
TI  - Effects of static magnetic fields on the physical and chemical properties of cell
      culture medium RPM1 1640.
AB  - RPMI 1640 culture medium was chosen to simulate body fluids, and after exposure
      to 0.085 approximately 0.092 T static magnetic fields (SMF), surface tension, pH,
      dissolved oxygen, and UV-visible spectrum were measured. Compared with the
      control group in the normal geomagnetic field, the pH value increased about 0.14
      units, dissolved oxygen increased about 14%, and the UV-visible spectra were
      different in peak intensity but without a shift in the peak. Surface tension
      showed no significant difference in the two groups. This data suggests that SMF
      can change some of the physical and chemical properties of RPM1 1640 solution,
      and may contribute to understanding biological effects of SMF.

PMID- 17454081
TI  - Comparison of bioactivity between GSM 900 MHz and DCS 1800 MHz mobile telephony
      radiation.
AB  - An increasing number of studies find that pulsed Radio Frequency (RF),
      electromagnetic radiation of both systems of digital mobile telephony,
      established and commonly used in Europe during the last years, GSM 900 MHz
      (Global System for Mobile telecommunications) and DCS 1800 MHz (Digital Cellular
      System), exert intense biological action on different organisms and cells
      (Hardell et al., 2006; Hyland, 2000; Kundi, 2004; Panagopoulos et al., 2004,
      2007). The two types of cellular telephony radiation use different carrier
      frequencies and give different frequency spectra, but they usually also differ in
      intensity, as GSM 900 MHz antennas operate at about double the power output than
      the corresponding DCS 1800 MHz ones. In our present experiments, we used a model
      biological system, the reproductive capacity of Drosophila melanogaster, to
      compare the biological activity between the two systems of cellular mobile
      telephony radiation. Both types of radiation were found to decrease significantly
      and non thermally the insect's reproductive capacity, but GSM 900 MHz seems to be
      even more bioactive than DCS 1800 MHz. The difference seems to be dependent
      mostly on field intensity and less on carrier frequency.

PMID- 17454082
TI  - Magnetobiology: the kT paradox and possible solutions.
AB  - The article discusses the so-called 'kT problem' with its formulation, content,
      and consequences. The usual formulation of the problem points out the paradox of
      biological effects of weak low-frequency magnetic fields. At the same time, the
      formulation is based on several implicit assumptions. Analysis of these
      assumptions shows that they are not always justified. In particular, molecular
      targets of magnetic fields in biological tissues may operate under physical
      conditions that do not correspond to the aforementioned assumptions.
      Consequently, as it is, the kT problem may not be an argument against the
      existence of non thermal magnetobiological effects. Specific examples are
      discussed: magnetic nanoparticles found in many organisms, long-lived rotational
      states of some molecules within protein structures, spin magnetic moments in
      radical pairs, and magnetic moments of protons in liquid water.

PMID- 17454083
TI  - A possible effect of electromagnetic radiation from mobile phone base stations on
      the number of breeding house sparrows (Passer domesticus).
AB  - A possible effect of long-term exposure to low-intensity electromagnetic
      radiation from mobile phone (GSM) base stations on the number of House Sparrows
      during the breeding season was studied in six residential districts in Belgium.
      We sampled 150 point locations within the 6 areas to examine small-scale
      geographic variation in the number of House Sparrow males and the strength of
      electromagnetic radiation from base stations. Spatial variation in the number of
      House Sparrow males was negatively and highly significantly related to the
      strength of electric fields from both the 900 and 1800 MHz downlink frequency
      bands and from the sum of these bands (Chi(2)-tests and AIC-criteria, P<0.001).
      This negative relationship was highly similar within each of the six study areas,
      despite differences among areas in both the number of birds and radiation levels.
      Thus, our data show that fewer House Sparrow males were seen at locations with
      relatively high electric field strength values of GSM base stations and therefore
      support the notion that long-term exposure to higher levels of radiation
      negatively affects the abundance or behavior of House Sparrows in the wild.

PMID- 17454084
TI  - Validity of functional stability limits as a measure of balance in adults aged 23
      73 years.
AB  - Functional stability limits (FSLs) are the percentage of the base of support that
      individuals are willing to extend their centre of pressure. The objective of this
      study was to provide construct validation of FSLs as a measure of balance by
      comparing FSLs across ages and with clinical balance measures. A total of 52
      participants volunteered. FSLs significantly decreased with age (p < 0.004).
      Correlations between FSLs and age (-0.56 < R < -0.73), multi-directional reach
      test (0.35 < R < 0.75) and anteroposterior and mediolateral centre of pressure
      excursions during static stance (-0.29 < R < -0.72) were generally moderate to
      good. Cronbach's alpha (0.75) indicated that these measures were internally
      consistent, i.e. measuring similar aspects of the balance construct. FSLs appear
      to be valid indicators of balance ability. They may be used in posture prediction
      models to determine when a step is required when reaching or lifting objects and
      in biomechanical models as a means of incorporating stability constraints.

PMID- 17454085
TI  - Accuracy and feasibility of using an electrogoniometer for measuring simple thumb
      movements.
AB  - The aim of this study was to determine the accuracy and feasibility of using an
      electrogoniometer (Model SG 110; Biometrics, Gwent, UK) for measuring simple
      thumb movements. Thumb disorders have been associated with the use of hand held
      devices such as mobile phones and these devices have become an integral part of
      modern life. In 15 young subjects, the measurements of eight flexion/extension
      (Flex/Ext) and adduction/abduction (Ad/Ab) thumb positions were compared between
      a thumb-mounted electrogoniometer and manual goniometer (which was taken as the
      benchmark). Group mean electrogoniometric measurement errors were below 4 degrees
      and 5 degrees for Ad/Ab and Flex/Ext measurements, respectively. During mobile
      phone use, the electrogoniometers measured differences in maximal joint angle
      postures, which appeared to be related to differences in mobile phone size. High
      movement velocities may increase the risk of musculoskeletal injury and the
      results indicated that Ad/Ab movements were twice the speed of Flex/Ext movements
      during mobile phone use. Electrogoniometers have utility for studying thumb
      movements during mobile phone use and may be used to evaluate other thumb-based
      input devices.

PMID- 17454086
TI  - Multi-digit maximum voluntary torque production on a circular object.
AB  - Individual digit-tip forces and moments during torque production on a
      mechanically fixed circular object were studied. During the experiments, subjects
      positioned each digit on a 6-dimensional force/moment sensor attached to a
      circular handle and produced a maximum voluntary torque on the handle. The torque
      direction and the orientation of the torque axis were varied. From this study, it
      is concluded that: (1) the maximum torque in the closing (clockwise) direction
      was larger than in the opening (counter clockwise) direction; (2) the thumb and
      little finger had the largest and the smallest share of both total normal force
      and total moment, respectively; (3) the sharing of total moment between
      individual digits was not affected by the orientation of the torque axis or by
      the torque direction, while the sharing of total normal force between the
      individual digit varied with torque direction; (4) the normal force safety
      margins were largest and smallest in the thumb and little finger, respectively.

PMID- 17454087
TI  - Assessment of physical demands and comparison of multiple exposure definitions in
      a repetitive sawmill job: board edger operator.
AB  - The primary objectives of the study were to 1) describe the physical exposures in
      a sawmill job with a high incidence of upper extremity musculoskeletal injuries
      in terms of multiple measures of posture, exertion and frequency (with varying
      definitions) and 2) to examine the comparability of those definitions. Surface
      electromyography and electrogoniometry were used to quantify the muscle demands
      and joint motions. Fourteen board edger operators from two sawmill facilities
      participated. All exposure assessments, with the exception of surface EMG
      measurements, were performed on the production lines. EMG measurements were
      performed within the facility in a location removed from the production line. The
      measurements showed that, on average, ranges of motions of 59, 102 and 84 degrees
      respectively in the planes of wrist radial/ulnar deviation, flexion/extension and
      pronation/supination were required to perform the job. Significant differences (p
      < .001) were observed between ranges of motion defined by peak postures and those
      due to peak postures required to perform the primary task only. Performance of
      the primary task required an average of 32% of maximum voluntary contraction from
      the forearm muscles assessed. Repetitions per day ranged, on average, from 2,015
      to 9,365. Incidence of reported upper extremity musculoskeletal injuries in the
      two facilities assessed was found to be higher with the greater total exposure.
      However, examination of the trend with a standardized measure of injury incidence
      was not possible.

PMID- 17454088
TI  - Knobology in use: an experimental evaluation of ergonomics recommendations.
AB  - The scientific basis for ergonomics recommendations for controls has usually not
      been related to active goal-directed use. The present experiment tests how
      different knob sizes and torques affect operator performance. The task employed
      is to control a pointer by the use of a control knob, and is as such an
      experimentally defined goal-directed task relevant to machine systems in general.
      Duration of use, error associated with use (overshooting of the goal area) and
      movement reproduction were used as performance measures. Significant differences
      between knob sizes were found for movement reproduction. High torques led to less
      overshooting as opposed to low torques. The results from duration of use showed a
      tendency that the differences between knob sizes were reduced from the first
      iteration to the second iteration. The present results indicate that the
      ergonomically recommended ranges of knob sizes might differently affect operator
      performance.

PMID- 17454089
TI  - A survey of high school students with ubiquitous access to tablet PCs.
AB  - This paper presents findings of a study of high school students participating in
      a tablet PC (TPC) programme. Primary areas of interest were students' experiences
      with and attitudes about the TPCs, physical discomfort associated with use of
      TPCs and temporal and task-driven patterns of TPC use. Data were collected via
      questionnaire and computer use-monitoring software. Results showed students'
      attitudes were generally quite positive towards the TPCs, although they did not
      tend to think TPCs had improved their grades, few disagreed that TPCs were a
      distraction in class, and visual and musculoskeletal discomfort was prevalent.
      Understanding how to use the TPC and recognizing its organizational capacity were
      associated with several positive attitudes towards the TPC, including making
      school more enjoyable. Children's exposure to computers will only increase, so
      study of the many dimensions of their impact is critical in order to understand
      what is effective, constructive and healthful for children.

PMID- 17454090
TI  - Evaluation of the effect of backpack load and position during standing and
      walking using biomechanical, physiological and subjective measures.
AB  - Recommendations on backpack loading advice restricting the load to 10% of body
      weight and carrying the load high on the spine. The effects of increasing load
      (0%-5%-10%-15% of body weight) and changing the placement of the load on the
      spine, thoracic vs. lumbar placement, during standing and gait were analysed in
      20 college-aged students by studying physiological, biomechanical and subjective
      data. Significant changes were: (1) increased thorax flexion; (2) reduced
      activity of M. erector spinae vs. increased activation of abdominals; (3)
      increased heart rate and Borg scores for the heaviest loads. A trend towards
      increased spinal flexion, reduced pelvic anteversion and rectus abdominis muscle
      activity was observed for the lumbar placement. The subjective scores indicate a
      preference for the lumbar placement. These findings suggest that carrying loads
      of 10% of body weight and above should be avoided, since these loads induce
      significant changes in electromyography, kinematics and subjective scores.
      Conclusions on the benefits of the thoracic placement for backpack loads could
      not be drawn based on the parameter set studied.

PMID- 17454091
TI  - The effect of reducing the number of EMG channel inputs on loading and stiffness
      estimates from an EMG-driven model of the spine.
AB  - Electromyography (EMG)-driven models of the spine routinely require between ten
      and 14 EMG channels to estimate joint load and stiffness variables. This study
      was designed to determine the sensitivity of common EMG-driven model outputs to
      the removal of individual EMG channels, and to test two adapted models driven
      from eight channels. A total of 11 male participants performed a variety of
      static exertions designed to resist either an applied trunk flexion or right side
      trunk lateral bend moment. In this study, 14 channels of EMG were recorded and
      used to drive a biomechanical model of the spine to predict L4-L5 joint load and
      stiffness values. The model was subsequently re-run after the removal of
      individual pairs of bilateral EMG channels, and again with eight-channel models
      in which the rectus abdominus, latissimus dorsi and multifidus EMG-channels were
      eliminated. Results showed that the eight-channel model provided estimates for
      the majority of output variables that did not differ substantially from the 14
      channel model, except in instances in which muscle force output was ramped to
      resist flexion moments. Estimates of the output variables were, in general,
      improved when multifidus fascicles were re-added to the model and driven from the
      lumbar erector spinae EMG sites.

PMID- 17454092
TI  - Maximal manual stretcher carriage: performance and recovery of male and female
      ambulance workers.
AB  - The effects of a maximal duration stretcher carriage on heart rate (HR), lactate
      concentration, hand steadiness and hand-grip strength were studied up to 72 h
      post-exercise in 17 male and 15 female military ambulance personnel. Using both
      hands for transport, the participants walked on a treadmill ergometer at a speed
      of 4.5 km/h. Force measurements at the handlebars yielded mean loads of 245 N (25
      kg) on each side. Each step on the treadmill induced additional force
      oscillations with peak forces up to 470 N corresponding to 130% (women) and 98%
      (men) of maximal voluntary contraction (MVC). In the males the maximal transport
      time was about twice the time in women (mean +/- SD: 184 +/- 51 s vs. 98 +/- 34
      s). These differences had no significant effect on HR and lactate values. The
      same applies to hand steadiness, which showed only a transient deterioration
      immediately after exercise. In contrast to these parameters, substantial
      differences were seen in hand-grip strength recovery. Immediately after exercise,
      maximal hand-grip strength decreased by 150 N (25% MVC) in the males vs. 50 N
      (14%) in the females. Irrespective of gender, individuals with larger hand-grip
      strength and longer carriage durations (range 120 s-280 s) showed the slowest
      strength recoveries (up to 72 h) as compared to 1 h of recovery in participants
      with short transport durations (range 27 s-120 s). These findings suggest that
      the increasing number of eccentric strains during uninterrupted stretcher
      carriage induces cumulative muscle damages that may require some days for
      complete recovery.

PMID- 17454093
TI  - Self-initiated and respondent actions in a simulated control task.
AB  - Operators often need to combine self-initiated and respondent actions. Two
      experiments dealt with the relative importance of these two types of actions as a
      function of the predictability of the system and the available information.
      Participants monitored three stations with different frequencies at which
      interventions were required. They were aided by warning cues, indicating the need
      for interventions. The frequencies of inspections of the stations, the response
      to the warning system and the overall performance were assessed for warning
      systems with different diagnostic properties. Participants adapted their
      responses to the relative frequency of required interventions and the reliance on
      and compliance to the warning system depended on the warning characteristics. The
      results support the notion that events, such as warning signals, have a complex
      role in the ongoing activity of the operator and are integrated into the set of
      information from external and internal sources that guide the operators' actions.

PMID- 17454097
TI  - 'If I had my residency I wouldn't worry': negotiating migration and HIV in
      Sydney, Australia.
AB  - OBJECTIVE: To describe the interrelationships between migration and resettlement,
      the Australian immigration system and living with HIV. METHOD: Data were
      collected through semi-structured, in-depth interviews with clients of the
      Multicultural HIV/AIDS and Hepatitis C Service and a sexual health clinic in the
      Sydney metropolitan area over an 18-month period in 2003-2004. RESULTS: Three
      major themes interwoven with migration were identified: HIV diagnosis, access to
      care and support, and forming social relations. Participants who applied for
      permanent residency in Australia rather than off-shore were usually diagnosed as
      HIV-positive as part of the health requirement for permanent residency. This
      jeopardized their prospect of staying in Australia and was at the same time a
      barrier to returning to the country of birth. It was also a barrier to accessing
      health care and support services and a major source of uncertainty. The meaning
      of an HIV-positive diagnosis was grounded in participants' knowledge about HIV
      from their country of birth: HIV infection was perceived as a terminal illness.
      Because of the stigma associated with HIV/AIDS, many had little or no contact
      with their ethnic communities in Australia. At the same time, they found it
      difficult to form new social relations in the Anglo-Celtic mainstream culture. A
      further problem was feeling torn between Australia and the promise of a better
      future, and the close emotional relationships with family and friends in the
      country of birth. CONCLUSION: New migrants with HIV need to negotiate two major
      life disruptions and two major uncertainties simultaneously: migration and HIV
      infection. In the Anglo-Celtic mainstream, language, cultural and financial
      barriers to health and support services should be removed or minimized. In ethnic
      communities, HIV-related stigma needs to be addressed to enable new migrants to
      form social relations in these communities and to rebuild their lives.

PMID- 17454098
TI  - Tobacco use among Native Hawaiian middle school students: its prevalence,
      correlates and implications.
AB  - OBJECTIVES: This study sought to explore whether Native Hawaiian primary ethnic
      identity is associated with cigarette use among Native Hawaiian middle school
      students. This study also explored whether social influence, psychosocial and
      cultural factors are associated with cigarette use in this sample. DESIGN: The
      data are from a cross-sectional survey of 1,695 Native Hawaiian middle school
      students at 22 public and private schools on five islands in Hawaii. A subset of
      these students from Native Hawaiian serving schools (N=136) completed additional
      measures of Hawaiian cultural variables. RESULTS: Based on univariate analyses,
      students whose primary ethnic identification was Hawaiian were more likely to
      have tried smoking (p<0.001) and to be current smokers (p<0.05) as compared to
      those classified as part Hawaiian. However, these findings were no longer
      significant in multivariate analyses. Social influence variables (i.e. peer and
      parental smoking) were most influential in explaining both prior and current
      smoking. Attendance at public school was also an important factor in explaining
      previous (OR=2.43; 95% CI=1.74, 3.38) and current (OR=7.20; 95% CI=4.58, 11.32)
      smoking behavior. Finally, cultural variables such as valuing Hawaiian folklore,
      customs, activities and lifestyle were largely unassociated with smoking behavior
      among Native Hawaiian middle school youth. CONCLUSIONS: Additional research is
      needed to understand what aspects of ethnic identity are associated with smoking
      behavior among Native Hawaiian youth. The strong influence of peer and parental
      smoking suggests the need for interventions that support the creation of social
      environments that discourage tobacco use.

PMID- 17454099
TI  - Language and use of cancer screening services among border and non-border
      Hispanic Texas women.
AB  - OBJECTIVES: Compared to other groups, Mexican American women screen less
      frequently for cervical and breast cancer. The most significant barriers reported
      by previous researchers include not having a usual source of care, lacking health
      insurance and English-language difficulties. In this paper we document and
      examine the factors associated with disparities in cancer screening between
      border and non-border residents by language of interview (Spanish or English)
      among Texas Hispanic women. We hypothesize that, controlling for socioeconomic
      and demographic characteristics, border residents are more likely to utilize
      screening services than non-border residents because of the greater presence of
      bilingual services in border counties. DESIGN: We follow the framework of the
      Behavioral Model for Vulnerable Populations proposed by Gelberg et al. (Health
      Services Research, vol. 34, no. 6, pp. 1273-1302, 2000). This model
      conceptualizes use of health care as an outcome of the interplay of predisposing,
      enabling and need factors and recognizes that vulnerable groups face additional
      barriers to health care utilization. Data come from the 2000, 2002 and 2004 Texas
      Behavioral Risk Factor Surveillance surveys. RESULTS: Group differences in cancer
      screenings are explained largely by socioeconomic characteristics and structural
      barriers to access. The significance of language of interview and of border
      residence disappear after controlling for factors such as health insurance,
      income and a usual source of care. CONCLUSION: Women who selected to be
      interviewed in Spanish were less likely to report age-appropriate cancer
      examinations, health insurance and a regular health care provider than those who
      selected to be interviewed in English. Disparities in cancer screenings among
      vulnerable Hispanic populations could be reduced by promoting the establishment
      of a regular health care provider.

PMID- 17454100
TI  - Antihypertensive adherence and drug class among Asian Pacific Americans.
AB  - OBJECTIVE: Research on adherence has emphasized the need to consider patient
      ethnicity when developing adherence plans. The objective of this study is to
      identify predictors of adherence for specific groups, particularly Asian
      Americans and Pacific Islanders. METHODS: We examined the factors, including drug
      class, associated with antihypertensive adherence for 28,395 adults in Hawaii
      (July 1999-June 2003) using health plan administrative data. The population
      included Japanese (n=13,836), Filipino (n=3,812), Chinese (n=2,280), Korean
      (n=450), part-Hawaiian (n=3,746) and white (n=3,920) patients. Members with
      antihypertensive medication in their possession >or=80% of the time were
      considered adherent. Multivariable logistic regression models were used to
      identify factors associated with adherence. RESULTS: Overall adherence rates were
      less than 65% among all racial/ethnic groups. After adjustment for patient age,
      gender, morbidity level, health plan type, isle of residence, comorbidities and
      year of treatment, Japanese were more likely than whites to adhere to
      antihypertensive therapy [OR=1.21 (1.14-1.29)], whereas Filipino [OR=0.69 (0.64
      0.74)], Korean [OR=0.79 (0.67-0.93)] and Hawaiian [OR=0.84 (0.78-0.91)] patients
      were less likely to adhere. These results were consistent across therapeutic
      class. Other patient factors associated with lower adherence included younger
      age, higher morbidity and history of heart disease. Patient factors were also
      significantly related to adherence, including gender and seeing a sub-specialist.
      Seeing a physician of the same ethnicity did not appear to improve adherence.
      CONCLUSIONS: Our findings of substantial disparities among Asian Pacific American
      subgroups highlight the need to examine subgroups separately. Future qualitative
      research is needed to determine appropriate interventions, particularly for
      Filipino, Korean and Hawaiian patients.

PMID- 17454101
TI  - Ethnic differences in the reliability and validity of a Panic Disorder Screen.
AB  - PURPOSE: The purpose of this study was to compare the reliability and validity of
      the Brief Panic Disorder Screen (BPDS) in samples of African American and
      Caucasian American primary care patients. METHODS: The BPDS was administered to
      295 patients scheduled to visit a primary care clinic for medical reasons. The
      presence or absence of a panic disorder diagnosis was established during a
      clinical interview with a psychiatrist. Measures of reliability (internal
      consistency) and validity (criterion validity) were compared between the two
      ethnic subgroups. FINDINGS: The BPDS demonstrated greater reliability and
      validity for Caucasians than African Americans. This effect was maintained even
      after controlling for group differences in key demographic variables. Differences
      between ethnic groups were apparent in both those with and those without panic
      disorder (PD). BPDS responses of African Americans with PD demonstrated very low
      internal consistency whereas a high rate of false positive PD diagnoses was
      related to higher than expected BPDS scores among African Americans without PD,
      particularly on the level of fear felt when experiencing shortness of breath or
      heart palpitations. DISCUSSION: These findings support the notion that cultural
      differences in the language and meaning associated with anxiety disorders
      contribute to the difficulty of accurately diagnosing PD in primary care
      populations. Additional research is needed to provide a better understanding of
      the cultural aspects of the anxiety experience. Such research would facilitate
      the development of better screening tools for panic and other anxiety disorders
      for ethnic minority primary care populations.

PMID- 17454102
TI  - In vivo comparison of cat alveolar and pulmonary intravascular macrophages:
      phagocytosis, particle clearance, and cytoplasmic motility.
AB  - The phagocytic and particle clearance function as well as the intracellular
      motility of cat pulmonary intravascular macrophages (PIMs) and pulmonary alveolar
      macrophages (PAMs) in situ were compared using ferrimagnetic gammaFe2O3 tracer
      particles and magnetometry. Submicrometric particles were injected intravenously
      (phagocytized by PIMs) or inhaled as respirable aerosols (phagocytized by PAMs).
      At various times post administration, the particles were magnetized with an
      external magnet. Then, the rate of decay of the remanent magnetic field
      (relaxation) reflecting the motion of particle-containing phagosomes was
      measured. There was a gradual increase in relaxation in PAMs, but a decrease in
      PIMs over the initial 7 hours, suggesting differences in rates of phagocytosis.
      From 7 to 42 days, relaxation parameters were constant in both cell types
      although faster in PAMs than in PIMs. Disappearance of retained particles in PIMs
      depended on the administered dose. Particles in PAMs cleared faster than
      particles in PIMs. Particle clearance from PIMs, but not from PAMs, was
      accompanied by translocation of particles to the liver and elsewhere. Our data
      show that PAMs have a slower rate of in vivo phagocytosis, higher cell motility,
      and faster particle clearance than PIMs.

PMID- 17454103
TI  - Effects of specific neutrophil elastase inhibitor, sivelestat sodium hydrate, in
      murine model of severe pneumococcal pneumonia.
AB  - An excessive amount of neutrophil elastase (NE) released from neutrophils
      accumulated in the lung can cause tissue damage, despite its importance to host
      defense against microbial pathogens in severe pneumonia. Therefore, NE inhibitors
      may reduce tissue damage in lungs with severe pneumonia. In this study, the
      efficacy of a specific NE inhibitor, sivelestat sodium hydrate (sivelestat), was
      examined using a murine model of severe pneumonia with Streptococcus pneumoniae.
      Male mice (CBA/JNCrj, aged 5 weeks) were inoculated intranasally with penicillin
      susceptible S. pneumonia (1.0 x 10(5) CFU/mouse). Sivelestat (3 mg/kg) or
      physiological saline was administered every 12 hours beginning at 12 hours after
      inoculation. Survival was primarily evaluated. Bronchoalveolar lavage fluid
      (BALF) and blood were collected at 30 hours after inoculation. Thus, cell counts
      in BALF and numbers of viable bacteria in blood were determined.
      Histopathological analysis was also performed. Sivelestat significantly prolonged
      survival when compared with the control group (P < .05), although all animals
      died within 4 days. Cell count and histopathological analysis indicated that
      sivelestat prevented the progression of lung inflammation, such as alveolar
      neutrophil infiltration and hemorrhage. Furthermore, the number of viable
      bacteria in blood was significantly lower in the sivelestat group than in the
      control group (5.69 +/- 0.27 and 6.75 +/- 0.32 log CFU/mL, respectively; mean +/-
      SEM, P < .01). Sivelestat prolonged survival in this model. A possible
      explanation for the improved survival is that sivelestat prevents tissue damage
      by inhibiting NE activity in the lung. Therefore, NE inhibitors may be useful for
      treating with patients with severe pneumonia.

PMID- 17454104
TI  - ST2 gene induced by type 2 helper T cell (Th2) and proinflammatory cytokine
      stimuli may modulate lung injury and fibrosis.
AB  - The authors have investigated gene expression of ST2 in the lung tissue of a
      bleomycin (BLM)-induced lung fibrosis model in vivo and in a human lung
      fibroblast cell line, WI38, and a human type II alveolar epithelial cell line,
      A549, reacting to proinflammatory and type 2 helper T cell (Th2)-type cytokine
      stimuli in vitro. The lung mRNA expression of interleukin (IL)-4, IL-5, IL-1beta,
      and tumor necrosis factor (TNF)-alpha increased significantly at day 7 after
      instillation of BLM, whereas interferon (IFN)-gamma mRNA expression did not
      increase. ST2 and transforming growth factor (TGF)-beta1 mRNA expression of the
      lung increased significantly between days 7 and 21, and increased to maximal
      levels at day 14 post-BLM challenge. ST2 mRNA expression statistically correlated
      with TGF-beta 1 mRNA expression. In addition, the combination of IL-1 beta, TNF
      alpha, and IL-4 had an additive effect on ST2 mRNA expression from A549 cells and
      WI38 cells. These findings suggest that soluble ST2 gene may increase, possibly
      reflecting the development of the inflammatory process and the Th2-type immune
      response in the fibrotic lung tissue, and may modulate a process of pulmonary
      fibrosis.

PMID- 17454105
TI  - Lung mechanics in the TIMP3 null mouse and its response to mechanical
      ventilation.
AB  - Tissue inhibitor of metalloproteinase-3 (TIMP3) null mice develop emphysema-like
      airspace enlargement due to an enzymatic imbalance. This study investigates how
      these abnormalities alter lung mechanics and the response to 2 different
      mechanical ventilation strategies. Phenotypically, TIMP3 null mice had increased
      compliance, and decreased resistance, tissue damping, and tissue elastance over
      wild-type controls. Decreased compliance and increased resistance were observed
      following the injurious ventilation strategy; however, the TIMP3 null response to
      both ventilation strategies was similar to wild-type mice. In conclusion, TIMP3
      null mice have significant alterations in lung mechanics; however, this does not
      affect their response to ventilation.

PMID- 17454106
TI  - Acrylamide formation in low-fat potato snacks and its correlation with colour
      development.
AB  - A recipe and technological process for the production of low-fat potato snacks
      (7% fat) was developed at the Institute of Food Technology of Plant Origin
      (Agricultural University of Poznan) using a combination of extrusion and a
      roasting process. Due to the character of the product, the level of acrylamide
      was analysed. At the same time, the influence of temperature and time of heating
      on acrylamide levels were monitored, as well as the correlation between colour
      development and acrylamide content. The level of acrylamide in low-fat potato
      snacks was 489 +/- 26 microg kg(-1), which is comparable to French fries,
      crackers and cookies but almost three times less than in potato chips, as
      analysed by other authors. It was also shown that temperature and heating time
      have a significant influence on acrylamide formation, with temperature having a
      stronger effect than time. Measurement of colour and acrylamide content at
      different temperatures and roasting times showed that there is a substantial
      correlation between lightness (L*), redness (a*), yellowness (b*) and acrylamide
      concentration as a function of time: r(2) = -0.995, r(2) = 0.996, r(2) = 0.998,
      respectively. Graduated increases in roasting temperature showed a correlation
      between lightness (L*) or redness (a*) and acrylamide concentration: r(2) = 
      0.947 and r(2) = 0.968. Yellowness (b*) was not correlated with acrylamide
      content as a function of temperature.

PMID- 17454107
TI  - Acrylamide content of selected Spanish foods: survey of biscuits and bread
      derivatives.
AB  - An overview of the acrylamide content in commercial biscuits and bread
      derivatives (bread sticks, bread crust, crackers) marketed in Spain is presented.
      Acrylamide was determined by stable isotope dilution LC-MS with an LOQ of 30
      microg kg(-1). Acrylamide content ranged from <LOQ-2085, <LOQ-151, <LOQ-296 and
      <LOQ-323 microg kg(-1) for biscuits, crisp bread, crackers and bread sticks,
      respectively. Acrylamide was significantly higher in samples when ammonium
      hydrogen carbonate had been used as a rising agent and high fibre content (>5%)
      used in the formulation, but lower when functional ingredients, such as polyols,
      were used. An estimation of the acrylamide dietary exposure related to biscuits
      and bread derivatives was calculated as 0.082 microg kg(-1) day(-1). Estimated
      dietary intake were 0.002 and 0.058 microg kg(-1) day(-1) for crackers and
      biscuits, respectively.

PMID- 17454108
TI  - Validation of an analytical method for the determination of spiramycin,
      virginiamycin and tylosin in feeding-stuffs by thin-layer chromatography and bio
      autography.
AB  - An inter-laboratory validation was carried out to determine the performance
      characteristics of an analytical method based on thin-layer chromatography (TLC)
      coupled to microbiological detection (bio-autography) for screening feed samples
      for the presence of spiramycin, tylosin and virginiamycin. Twenty-four samples
      including blank samples and samples with concentrations of the target analytes
      ranging between 1 and 5 mg kg(-1) (expressed in microbiological activity) were
      analysed by seven laboratories participating in the study. The required detection
      limit was 1 mg kg(-1) (expressed in microbiological activity). For spiramycin,
      acceptable values for the sensitivity (at least 95%) indicating the rate of
      correct positive results were obtained for samples containing this substance at
      or above 2 mg kg(-1), whereas at 1 mg kg(-1), the sensitivity rate dropped to
      about 70%. Therefore, it was concluded that the detection limit was 2 mg kg(-1).
      For tylosin and virginiamycin, acceptable values of the sensitivity were obtained
      for all concentrations including 1 mg kg(-1). Therefore, the method fulfils the
      criterion regarding the required sensitivity at the target detection limit for
      tylosin and virginiamycin.

PMID- 17454109
TI  - Recoveries of four representative organophosphorus pesticides from 18 plant
      products belonging to different botanical categories: implications for matrix
      effects.
AB  - A study of the matrix effect was performed in order to evaluate the influence of
      some matrices on the gas chromatographic responses of representative
      organophosphorus insecticides. In particular, three fortification levels and the
      maximum residual level of four organophosphorus pesticide standard solutions were
      added into 18 matrices (15 belonging to five specific botanical categories and
      three botanically unclassified). The recoveries of the examined pesticides were
      determined using a simple official multiresidue method of detection, without any
      additional clean-up step. Recoveries were estimated based on standards prepared
      in solvent. The recovery percentages of the most polar pesticides, especially
      methamidophos (20.2-288.4%), were much higher than those of non-polar ones
      (chlorpyrifos and methidathion 25.7-136.4 and 37.6-292.6%, respectively), except
      for quince. Pronounced matrix effects (>120%) were observed to the lowest
      fortification levels (maximum residual levels established by the European Union),
      of dimethoate and methamidophos (i.e. the most polar analytes) in the majority of
      product extracts. Furthermore, it was proved that there is no correlation between
      the classification of plant products, according to their botanical
      characteristics, and the recoveries of pesticides in the equivalent extracts.
      Indeed, there were significant differences in the recoveries of pesticides in
      extracts, derived from matrices belonging to the same botanical group (especially
      in the categories of pome fruits and citrus). Consequently, it was shown that,
      under the examined conditions, obtaining recovery data, derived from only one
      representative matrix, with the purpose to validate an official method in its
      botanical category is, possibly, an erroneous practice.

PMID- 17454110
TI  - Carry-over of Fusarium toxins (deoxynivalenol and zearalenone) from naturally
      contaminated wheat to pigs.
AB  - The frequent contamination of grain with the Fusarium toxins, deoxynivalenol
      (DON) and zearalenone (ZON), is an important issue in animal and human nutrition.
      However, data on the exposure of humans to these toxins through consumption of
      animal tissues exposed to Fusarium toxins (carry-over) are fragmentary.
      Therefore, residues of DON, ZON and their metabolites were determined in tissues
      and body fluids of pigs (female and castrated male) from a fattening trial. Pigs
      were fed a control (n = 6, 0.24 mg DON and 0.009 mg ZON per kg diet as fed) or a
      Fusarium toxin-contaminated diet (n = 12, 6.68 mg DON and 0.056 mg ZON per kg
      diet as fed) either ad libitum or for restrictive consumption for 12 weeks. After
      slaughter (96.3 +/- 11.6 kg live weight), the concentrations of DON and its
      metabolite, de-epoxy-DON, were measured in serum, bile, liver, kidney, musculus
      longissimus and back fat, while ZON and its metabolites, alpha- and beta
      zearalenol (alpha-/beta-ZOL), were determined in serum, bile and liver. The mean
      carry-over factor of DON + de-epoxy-DON, defined as the concentration of both
      substances in the tissue/fluid divided by the DON concentration in the diet, for
      all pigs decreased from bile (0.1046 +/- 0.0653) >> kidney (0.0151 +/- 0.0070) >
      liver (0.0057 +/- 0.0043) > serum (0.0023 +/- 0.0018) > muscle (0.0016 +/-
      0.0016) >> back fat (0.0002 +/- 0.0004). The time interval between the end of
      feeding and slaughter had no consistent effect on DON + de-epoxy-DON
      concentrations in the analysed specimen of Fusarium toxin-exposed pigs fed
      restrictively. No transfer of ZON and its metabolites could be observed into
      serum of pigs, while the mean carry-over factors of ZON + alpha-ZOL + beta-ZOL
      were 0.0094 +/- 0.0123 and 4.0 +/- 2.2 for liver and bile, respectively.
      Therefore, it can be concluded that serum is a reliable indicator for DON
      exposure, but an inappropriate parameter to deduce ZON exposure, which is better
      represented by bile concentration of ZON + alpha-ZOL + beta-ZOL. However, the
      exposure risk to humans by consumption of edible tissues of animals exposed to
      Fusarium toxins is negligible compared to the direct consumption of grain-based
      food.

PMID- 17454111
TI  - Occurrence of fumonisins B1 and B2 in Portuguese maize and maize-based foods
      intended for human consumption.
AB  - Fumonisin B(1) (FB(1)) and fumonisin B(2) (FB(2)) are mycotoxins mainly produced
      by Fusarium verticillioides and Fusarium proliferatum, which are field pathogens
      of maize. A survey was conducted on the incidences of FB(1) and FB(2) in both
      maize and derived products purchased in Portugal. The analytical method involved
      extraction with methanol-water, clean-up by immunoaffinity column and
      derivatization with naphthalene-2,3-dicarboxaldehyde. Determination was carried
      out by high-performance liquid chromatography (HPLC) with spectrofluorimetric
      detection, with liquid chromatography/mass spectrometry (LC/MS) confirmation. The
      presence of FB(1) and FB(2) was determined in 67 samples of maize and maize-based
      foods, such as flour, semolina, starch, sweet maize, cornflakes and other
      breakfast cereals, and snacks collected in 2005. FBs were found in 15 samples at
      concentrations ranging from 113 to 2026 microg kg(-1). Two of the samples showed
      higher contamination levels than the limits established by the European
      Commission Regulation. None of the samples contained levels of fumonisins that
      would lead to an exposure exceeding the tolerable daily intake (TDI).

PMID- 17454112
TI  - Suppression of ochratoxin biosynthesis by naturally occurring alkaloids.
AB  - The effects of four alkaloids on the biosynthesis of ochratoxin A (OTA),
      ochratoxin B (OTB) and citrinin were examined on four OTA-producing aspergilli:
      Aspergillus auricomus, A. sclerotiorum and two isolates of A. alliaceus. Piperine
      and piperlongumine, natural alkaloids of Piper longum, significantly inhibited
      OTA production at 0.001% (w/v) for all aspergilli examined. Piperine and
      piperlongumine affected the polyketide synthesis step of OTA production and
      inhibited production of citrinin. Curcumin, a constituent of tumeric, completely
      inhibited mycelial growth of A. alliaceus isolate 791 at 0.1% (w/v) and decreased
      OTA production by approximately 70% at 0.01% (w/v). Sesamin, a constituent of
      sesame oil, inhibited OTA and OTB production by 60 and 45%, respectively, at 0.1%
      (w/v), showing its effect was on chloroperoxidase and polyketide synthase
      activity. The potential advantage of these natural products to reduce ochratoxin
      contamination of agricultural commodities is discussed.

PMID- 17454113
TI  - Application and validation of a clean-up tandem assay column for screening
      ochratoxin A in cocoa powder.
AB  - A rapid antibody-based assay for the detection of ochratoxin A in cocoa powder is
      described, involving sequential clean-up and visual detection of the toxin
      ("clean-up tandem assay column"). The screening test was developed to have a cut
      off level of 2 microg kg(-1) and was shown to have false positive and false
      negative rates of 10 and 2%, respectively. Analysis of six samples can be carried
      out in the field in approximately 30 min by untrained workers. Using the proposed
      rapid screening test, 10 retail cocoa powders were found to contain no detectable
      levels of ochratoxin A (<2 microg kg(-1)). These samples were also found to be
      negative (<2 microg kg(-1)) when analysed using an LC-MS/MS method.

PMID- 17454114
TI  - Screening of fermentative bacteria for their ability to bind and biotransform
      deoxynivalenol, zearalenone and fumonisins in an in vitro simulated corn silage
      model.
AB  - Fermentative bacteria can potentially be utilized to detoxify corn silage
      contaminated by Fusarium toxins. The objective of the present study was to test a
      large number of these bacteria for their ability to bind and/or biotransform
      deoxynivalenol (DON), zearalenone (ZEN) and fumonisins B(1) and B(2) (FB(1),
      FB(2)) in conditions simulating corn silage. A total of 202 strains were screened
      in contaminated, pH 4, corn infusion inoculated with 5 x 10(8) CFU ml(-1). Eight
      Lactobacilli and three Leuconostoc biotransformed ZEN into alpha-zearalenol, but
      no biotransformation was detected for DON and fumonisins. In contrast, most
      strains were capable of binding Fusarium toxins. The most effective genera were
      Streptococcus and Enterococcus, capable of binding up to 33, 49, 24 and 62% of
      DON, ZEN, FB(1) and FB(2), respectively. The ability to bind Fusarium toxins
      seems to be a common property of fermentative bacteria and could help to decrease
      their toxicity in animals.

PMID- 17454115
TI  - In vitro microbial metabolism of fumonisin B1.
AB  - There is a lack of information on the effect of swine caecal microbiota on
      fumonisin metabolism. In this in vitro study, the biotransformation of fumonisin
      B(1) (FB(1)) by the gut microbiota of adult, healthy pigs was examined.
      Suspensions of caecal contents and McDougall buffer solution were incubated
      anaerobically with pure FB(1) for 0, 12, 24, 48 and 72 h. After 48 h, the
      conversion of FB(1) to partially hydrolysed FB(1) (46%) was nearly equal to the
      percentage ratio of FB(1), while by 72 h it was 49%. In vitro, the conversion of
      fumonisin B(1) to aminopentol was less than 1%. The results show that the caecal
      microbiota are capable of transforming fumonisin B(1) to the above metabolites.
      Further studies on FB(1) metabolism in the small intestine are clearly justified.

PMID- 17454116
TI  - Dietary uptake of dioxins (PCDD/PCDFs) and dioxin-like PCBs in Spanish
      aquacultured turbot (Psetta maxima).
AB  - The human population is exposed to dioxins (PCDD/Fs) and dioxin-like
      polychlorinated biphenyls (dl-PCBs) mainly through diet; bioaccumulation and
      biomagnification in aquatic environment results in fishery products and by
      products being an important vector to humans. The determination of PCDD/Fs and dl
      PCBs in fillets of young turbots (Psetta maxima) (0-2 years) from aquaculture
      plant (Galicia, Spain) (N = 21) and in feeding stuffs were carried out, and
      dietary accumulation values and lipid-normalized biomagnification factors (BMF)
      relating concentration in fish and in feed were calculated. Levels found in
      feeding stuffs (0.5 pg TEQ-PCDD/F/g and 1.6 pg TEQ-dl-PCB/g), and turbots (0.13
      0.27 pg TEQ-PCDD/F/g fresh weight and 0.35-1.2 pg TEQ-dl-PCB/g fresh weight) were
      below maximum permitted levels set by EC. Levels of toxic compounds in feeding
      stuff are reflected in fish fillets; predominant isomers are 2,3,7,8-TCDF, OCDD,
      1,2,3,7,8-PeCDF, 2,3,4,7,8-PeCDF and 1,2,3,4,6,7,8-HpCDD, and PCBs 118, 105, 156
      and 167. Relevant compounds accounting for total toxicity are the same congeners
      in feeding stuff and turbots: 2,3,4,7,8- PeCDF; 2,3,7,8-TCDF; 2,3,7,8-TCDD and
      1,2,3,7,8-PeCDD, and PCB 126. Higher accumulation efficiency values were obtained
      for dl-PCBs (30-46%); tetra- and penta-chloro substituted PCDD/Fs showed the
      highest values (27-34%) of the PCDD/F group. Biomagnification was shown for these
      compounds (BMF around 1.5).

PMID- 17454117
TI  - Polycyclic aromatic hydrocarbons (PAHs) in meat products and estimated PAH intake
      by children and the general population in Estonia.
AB  - The concentrations of benzo[a]pyrene and 11 other polycyclic aromatic
      hydrocarbons (PAHs) were analysed from 322 commercial, cured meat products and 14
      home-grilled meat samples as part of the Estonian food safety monitoring
      programme during 2001-2005. The maximum acceptable concentration of 5 microg kg(
      1) for benzo[a]pyrene was exceeded in 3.4% of samples. The highest PAH
      concentrations were detected in home-grilled pork samples. Using of disposable
      grilling unit resulted in 1.6 times higher PAH concentrations compared to the
      traditional wood-burning grill. The average intake of benzo[a]pyrene and sum of
      12 PAHs from meat products was estimated for children (age 1-16 years) on the
      basis of an individual food consumption questionnaire and, for the general
      population, based on national food consumption data. The highest total PAH
      concentrations detected were 16 microg kg(-1) in smoked meat and ham, 19 microg
      kg(-1) in smoked sausage and 6.5 microg kg(-1) in smoked chicken samples. Since
      smoking and grilling are prevalent meat-cooking methods in Estonia, the impact of
      meat products is assessed to be significant in overall PAH intake.

PMID- 17454118
TI  - 2-Isopropylthioxanthone (2-ITX) in food and food packaging materials on the
      German market.
AB  - To elucidate the occurrence of the photo-initiator, 2-isopropylthioxanthone (2
      ITX), more than 100 food products on the German market, packed in cartons,
      plastic cups and foils, were investigated. For this, a rapid method to detect 2
      ITX in food packaging materials was established. In case of positive findings,
      the accompanying foodstuffs were analysed in a subsequent step using different
      extraction methods, depending on the fat content of the food. Determination of
      the photo-initiator was done by high-performance liquid chromatography with diode
      array and fluorescence detection (HPLC-DAD/FLD). Recoveries ranged between 94 and
      106% for non-fatty (RSD <or= 1.1) and between 80 and 105% for fatty foods (RSD
      <or= 8.5). The limit of detection and limit of quantification were determined to
      2 and 5 microg l(-1). 2-ITX was detected in 36 of 137 packages (26%) and
      significant migration occurred in 75% of the packaging materials tested positive.
      The levels of 2-ITX ranged up to 357 microg kg(-1) in orange juice.

PMID- 17454120
TI  - The potential pitfalls of using 1,1-diphenyl-2-picrylhydrazyl to characterize
      antioxidants in mixed water solvents.
AB  - Approaching living systems, aqueous solutions are appropriate to characterize
      antioxidants, whereas the frequently used standard 1,1-diphenyl-2-picrylhydrazyl
      (DPPH) is insoluble in water. Therefore, mixed water-ethanol solvents were
      investigated using the electron paramagnetic resonance (EPR) spectroscopy. Two
      forms of DPPH were identified: at higher ethanol ratios a quintet spectrum
      characteristic of solutions, and at lower ratios, a singlet spectrum typical for
      solid DPPH, were found. Mixed solvents with 0-50% (v/v) water reproduced the same
      antioxidant equivalent points well and the reaction rate between DPPH and the
      antioxidant may increase considerably with increasing water ratios, as
      demonstrated using vitamin E as an antioxidant. But at still higher water ratios
      (70-90% (v/v)) the antioxidant activities dropped, since a part of the DPPH in
      the aggregated form does not react sufficiently with the antioxidants.
      Characteristics of the most common antioxidants were determined in ethanol or its
      50% (v/v) aqueous solution.

PMID- 17454121
TI  - CoCl(2)-simulated hypoxia in skeletal muscle cell lines: Role of free radicals in
      gene up-regulation and induction of apoptosis.
AB  - Since it was suggested that cobalt chloride (CoCl(2)) could mimic the O(2)
      sensing role of mitochondria by increasing reactive oxygen species (ROS)
      generation during normoxia, we studied the correlation between CoCl(2)-generation
      of free radicals and the induction of a hypoxic cellular response in myogenic
      cell lines. In both L6C5 and C2C12 cell lines, exposure to CoCl(2) induced an
      increase of intracellular oxidants, the accumulation of HIF-1alpha protein, and
      the expression of vascular endothelial growth factor (VEGF) and/or iNOS genes. On
      the other hand, only ascorbic acid, but not trolox, was effective in lowering the
      CoCl(2) gene up-regulation. Neither the cytotoxicity nor the apoptosis induced by
      CoCl(2) in skeletal muscle cells were modified by culture supplementation with
      either ascorbic acid or trolox. Thus, CoCl(2) treatment of myogenic cell lines
      may represent a useful and convenient in vitro model to study gene modulation
      induced by hypoxia in skeletal muscle, although cellular loss induced by this
      metal may involve mechanisms other than HIF-1alpha stabilization. It is unlikely,
      however, that ROS would represent the main mediators of CoCl(2) effects on muscle
      cells.

PMID- 17454122
TI  - Inhibitory and enhancing effects of NO on H(2)O(2) toxicity: dependence on the
      concentrations of NO and H(2)O(2).
AB  - Nitric oxide (NO) has been shown to both enhance hydrogen peroxide (H(2)O(2))
      toxicity and protect cells against H(2)O(2) toxicity. In order to resolve this
      apparent contradiction, we here studied the effects of NO on H(2)O(2) toxicity in
      cultured liver endothelial cells over a wide range of NO and H(2)O(2)
      concentrations. NO was generated by spermine NONOate (SpNO, 0.001-1 mM), H(2)O(2)
      was generated continuously by glucose/glucose oxidase (GOD, 20-300 U/l), or added
      as a bolus (200 microM). SpNO concentrations between 0.01 and 0.1 mM provided
      protection against H(2)O(2)-induced cell death. SpNO concentrations >0.1 mM were
      injurious with low H(2)O(2) concentrations, but protective at high H(2)O(2)
      concentrations. Protection appeared to be mainly due to inhibition of lipid
      peroxidation, for which SpNO concentrations as low as 0.01 mM were sufficient.
      SpNO in high concentration (1 mM) consistently raised H(2)O(2) steady-state
      levels in line with inhibition of H(2)O(2) degradation. Thus, the overall effect
      of NO on H(2)O(2) toxicity can be switched within the same cellular model, with
      protection being predominant at low NO and high H(2)O(2) levels and enhancement
      being predominant with high NO and low H(2)O(2) levels.

PMID- 17454123
TI  - The endogenous neurotransmitter, serotonin, modifies neuronal nitric oxide
      synthase activities.
AB  - Serotonin, an important neurotransmitter, is colocalized with neuronal nitric
      oxide synthase (nNOS), a homodimeric enzyme which catalyzes the production of
      nitric oxide (NO(.-)) and/or oxygen species. As many interactions have been
      reported between the nitrergic and serotoninergic systems, we studied the effect
      of serotonin on nNOS activities. Our results reveal that nNOS is activated by
      serotonin as both NADPH consumption and oxyhemoglobin (OxyHb) oxidation were
      enhanced. The generation of L-citrulline from L-arginine (L-Arg) was not affected
      by serotonin in the range of 0-200 microM, suggesting an additional production of
      oxygen-derived species. But 5-hydroxytryptamine (5HT) induced the formation of
      both O and H(2)O(2) by nNOS, as evidenced by electron paramagnetic resonance
      (EPR) and by using specific spin traps. Overall, these results demonstrate that
      serotonin is able to activate nNOS, leading to the generation of reactive oxygen
      species (ROS) in addition to the NO(.-) production. Such a property must be
      considered in vivo as various nNOS-derived products mediate different signaling
      pathways.

PMID- 17454124
TI  - Oxidative stress implication in a new phenotype of amyotrophic quadricipital
      syndrome with cardiac involvement due to lamin A/C mutation.
AB  - This study aimed at evaluating OS in an amyotrophic quadricipital syndrome with
      cardiac impairment in a family of 80 members with a mutation in lamin A/C gene.
      Twelve patients had cardiac involvement (5 cardiac and skeletal muscles
      impairment). OS was evaluated in blood samples (thiobarbituric acid-reactive
      substances (TBARS), carbonylated proteins (PCO)) 6 "affected patients" with
      phenotypic and genotypic abnormalities without heart failure and 3 "healthy
      carrier" patients. OS was higher in affected patients than in healthy, as shown
      by the higher TBARS and PCO values. Patients with cardiac and peripheral myopathy
      exhibited a higher OS than patients with only cardiac disease (TBARS: 1.73 +/-
      0.05 vs. 1.51 +/- 0.04 mmol/l (p = 0.051), PCO: 2.73 +/- 0.34 vs. 0.90 +/- 0.10
      nmol/mg protein (p = 0.47)), and with healthy carriers patients (TBARS: 1.73 +/-
      0.05 vs. 1.16 +/- 0.14 mmol/l (p = 0.05), PCO: 2.73 +/- 0.34 vs. 0.90 +/- 0.20
      nmol/mg protein (p = 0.47)). OS may thus contribute to the degenerative process
      of this laminopathy. ROS production occurs, prior to heart failure symptoms. We
      suggest that the extent activation may also promote the variable phenotypic
      expression of the disease.

PMID- 17454125
TI  - Identification of free radicals of glycerophosphatidylcholines containing omega-6
      fatty acids using spin trapping coupled with tandem mass spectrometry.
AB  - Metal-catalysed radical oxidation of diacyl-glycerophosphatidylcholines (GPC)
      with omega-6 acyl polyunsaturated fatty acids (PAPC, palmitoyl-arachidonoyl
      glycerophosphatidylcholine and PLPC, palmitoyl-lineloyl
      glycerophosphatidylcholine) was studied. Free radical oxidation products were
      trapped by spin trapping with 5,5-dimethyl-1-pyrrolidine-N-oxide (DMPO) and
      identified by electrospray mass spectrometry (ES-MS). The spin adducts of
      oxidised GPC containing one and two oxygen atoms and one and two DMPO molecules
      were observed as doubly charged ions. Structural characterisation by tandem mass
      spectrometry (MS/MS) of these ions revealed product ions corresponding to loss of
      the acyl chains (sn-1-palmitoyl and sn-2-oxidised spin adduct of lineloyl or
      arachidonoyl), loss of the spin trap (DMPO) and product ions attributed to
      oxidised sn-2 fatty acid spin adduct (lineloyl and arachidonoyl). Product ions
      formed by homolytic cleavages near the spin trap and also from 1,4 hydrogen
      elimination cleavages involving the hydroxy group in the sn-2 fatty acid spin
      adduct allowed to infer the nature of the radical. Altogether, the presence of
      GPC hydroxy-alkyl/DMPO and hydroxy-alkoxyl/DMPO spin adducts was proposed.

PMID- 17454126
TI  - Trolox protection of myelin membrane in hydrogen peroxide-treated mature
      oligodendrocytes.
AB  - Oligodendrocytes have the highest rate of metabolic activity in the brain and are
      highly vulnerable to oxidative stress. In this work we determined the protective
      effect of Trolox, a water-soluble analogue of vitamin E, and insulin, a peptide
      shown to be neuroprotective, in oligodendrocyte lesion induced by hydrogen
      peroxide (H(2)O(2)). Exposure of primary cultures of rat oligodendrocytes to
      H(2)O(2) dose-dependently decreased their reducing capacity, as determined by the
      MTT assay. H(2)O(2) (100 muM) had no effect on Bax levels, active-caspase-3, DNA
      fragmentation or lactate dehydrogenase (LDH) leakage. Nevertheless, under these
      conditions, H(2)O(2) decreased the levels of myelin basic protein (MBP), used as
      a marker for oligodendrocyte myelin membrane. Treatment with insulin alone
      increased MBP levels, but no changes were observed in the presence of insulin
      plus H(2)O(2). In contrast, incubation with Trolox completely prevented H(2)O(2)
      induced decrease in MBP expression, suggesting that vitamin E analogues may
      prevent against oligodendrocyte oxidative damage.

PMID- 17454127
TI  - Reactive oxygen and nitrogen species are involved in sorbitol-induced apoptosis
      of human erithroleukaemia cells K562.
AB  - In this study, we found that production of both reactive oxygen (ROS) and
      nitrogen (RNS) species is a very early event related to treatment with
      hyperosmotic concentration of sorbitol. The production of nitric oxide (NO) was
      paralleled by the increase of the mRNA and protein level of the inducible form of
      the nitric oxide synthase (iNOS). ROS and RNS enhancement, process concomitant to
      the failure of mitochondrial trans-membrane potential (DeltaPsi), was necessary
      for the induction of apoptosis as demonstrated by the protection against sorbitol
      mediated toxicity observed after treatment with ROS scavengers or NOS inhibitors.
      The synergistic action of ROS and RNS was finally demonstrated by pre-treatment
      with rosmarinic acid that, by powerfully buffering both these species, prevents
      impairment of DeltaPsi and cell death. Overall results suggest that the
      occurrence of apoptosis upon sorbitol treatment is an event mediated by
      oxidative/nitrosative stress rather than a canonical hyperosmotic shock.

PMID- 17454128
TI  - Photosensitized DNA damage induced by NADH: site specificity and mechanism.
AB  - Increasing evidence reveals the carcinogenicity of UVA radiation. We demonstrated
      that UVA-irradiated NADH induced damage to (32)P-labeled DNA fragments obtained
      from the p53 gene in the presence of Cu(II). Formamidopyrimidine glycosylase
      (Fpg)-sensitive lesions were formed at guanine residues, whereas piperidine
      labile lesions occurred frequently at thymine residues. Formation of 8-oxo-7,8
      dihydro-2'-deoxyguanosine (8-oxodG), upon UVA exposure in the presence of Cu(II),
      increased depending on NADH concentration. Catalase and bathocuproine, a Cu(I)
      specific chelator, inhibited the DNA damage, suggesting the involvement of
      reactive species derived from H(2)O(2) and Cu(I). UVA-irradiated riboflavin
      induced DNA cleavage through electron transfer at 5' guanine of the 5'-GG-3'
      sequence with both Fpg and piperidine treatments; Fpg induced less cleavage at
      the guanine residues than piperidine. These results imply that NADH may
      participate as an endogenous photosensitizer in UVA carcinogenesis via H(2)O(2)
      generation, producing metal-mediated mutagenic lesions such as 8-oxodG.

PMID- 17454129
TI  - Methyl vinyl ketone induces apoptosis in murine GT1-7 hypothalamic neurons
      through glutathione depletion and the generation of reactive oxygen species.
AB  - alpha,beta-Unsaturated carbonyl compounds have been implicated in a number of
      environmentally-related diseases. Often, the presence of alpha,beta-unsaturated
      carbonyl functionality as part of either an aliphatic or cyclic structure is
      considered a structural alert for cytotoxicity. We examined the cytotoxicity of
      methyl vinyl ketone (MVK), an aliphatic, straight-chain alpha,beta-unsaturated
      carbonyl compound, in murine GT1-7 hypothalamic neurons. In addition to its
      widespread environmental occurrence, MVK was selected due to its extensive use in
      the chemical industry. Also, MVK is a close structural analog of
      hydroxymethylvinyl ketone that, in part, mediates the cytotoxic effects of 1,3
      butadiene in vivo. It was found that MVK at low micromolar concentrations induced
      extensive cell death that retained key features of apoptosis such as chromatin
      condensation and DNA fragmentation. The MVK-induced apoptosis was associated with
      depletion of glutathione, disruption of mitochondrial transmembrane potential,
      and increased generation of reactive oxygen species (ROS). Supplementation of
      neuronal cells with Trolox offered partial, but significant, protection against
      the MVK-induced cytotoxicity, presumably due to scavenging of ROS in situ. The
      suggested sequence of events in the MVK-induced apoptosis in neuronal cells
      involves the depletion of cellular glutathione followed by an increased
      generation of ROS and finally the loss of mitochondrial function.

PMID- 17454130
TI  - The identification of antioxidants in dark soy sauce.
AB  - Soy sauce is a traditional fermented seasoning in Asian countries, that has high
      antioxidant activity in vitro and some antioxidant activity in vivo. We attempted
      to identify the major antioxidants present, using the 2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay as a guide. 3-Hydroxy-2-methyl
      4H-pyran-4-one (maltol) was one of several active compounds found in an ethyl
      acetate extract of dark soy sauce (DSS) and was present at millimolar
      concentrations in DSS. However, most of the antioxidant activity was present in
      colored fractions, two of which (CP1 and CP2) were obtained by gel filtration
      chromatography. Their structural characteristics based on nuclear magnetic
      resonance (NMR) and electrospray-ionization time-of-flight mass spectrometry (ESI
      TOF-MS) analysis suggest that carbohydrate-containing pigments such as
      melanoidins are the major contributors to the high antioxidant capacity of DSS.

PMID- 17454131
TI  - S-allyl cysteine prevents CCl(4)-induced acute liver injury in rats.
AB  - Aged garlic extract (AGE) possesses multiple biological activities. We evaluated
      the protective effect of S-allyl cysteine (SAC), one of the organosulfur
      compounds of AGE, against carbon tetrachloride (CCl(4))-induced acute liver
      injury in rats. SAC was administrated intraperitoneally (50-200 mg/kg). SAC
      significantly suppressed the increases of plasma ALT and LDH levels. SAC also
      attenuated histological liver damage. CCl(4) administration induced lipid
      peroxidation accompanied by increases in the plasma malondialdehyde and hepatic 4
      hydroxy-2-nonenal levels, and SAC dose-dependently attenuated these increases.
      The hepatic total level of hydroxyoctadecadienoic acid (HODE), a new oxidative
      stress biomarker, was closely correlated with the amount of liver damage. These
      results suggest that SAC decreased CCl(4)-induced liver injury by attenuation of
      oxidative stress, and may be a better therapeutic tool for chronic liver disease.

PMID- 17454132
TI  - A hypocaloric diet enriched in legumes specifically mitigates lipid peroxidation
      in obese subjects.
AB  - Legume intake could specifically protect against lipid peroxidation in addition
      to the effects associated to weight loss when included in hypocaloric diets.
      Thus, 30 obese subjects (age: 36 +/- 8 years and BMI: 32.0 +/- 5.3 kg/m(2)) were
      nutritionally treated by a 8-week energy restriction ( - 30% energy expenditure)
      with a legume enriched diet (4 days/week servings, [image omitted] ) or without
      legumes (control diet (CD), [image omitted] ). Body weight, circulating
      cholesterol, oxidized LDL (ox-LDL), malondialdehyde (MDA) and urinary 8
      isoprostane F(2alpha) (8-iso-PGF(2alpha)) were measured at baseline and at
      endpoint. After the nutritional intervention, all obese subjects lost weight,
      specially those individuals who followed the legumes-enriched diet as compared to
      the CD ( - 7.7 +/- 3 vs. - 5.3 +/- 2.7%; p = 0.023), which was accompanied by
      marked decreases in total cholesterol levels (p < 0.001) and statistically
      significant diet-related reductions on plasma ox-LDL, plasma MDA and urinary 8
      iso-PGF(2alpha) output. Therefore, a balanced diet with moderate caloric
      restriction including 4 day/week legume servings empowered the oxidative stress
      improvement related to weight loss through a reduction in lipid peroxidation as
      compared to a control hypocaloric diet.

PMID- 17454133
TI  - Methyl glyoxal elevation is associated with oxidative stress in rheumatoid
      arthritis.
AB  - Methyl glyoxal (MG), a metabolic hazard plays a role in pathogenesis of different
      diseases. We studied the role of MG in cellular oxidative and carbonyl stress in
      rheumatoid arthritis (RA). 148 RA patients were divided into subgroups according
      to disease severity, RA factor status and age. They were acute, remission,
      seropositive, seronegative and JRA group. About 88 normal, young, healthy
      individuals were taken as control. We estimated serum level of total antioxidant
      status (TAS), total thiol, GSH, MG, carbonyl compounds and TBARS level of normal
      control and RA. The synovial fluid (SF) level of above parameters have been also
      evaluated in RA. Our observation suggests that MG elevation is associated with
      increased level of TBARS and decreased level of GSH in all RA subgroups than
      normal control. The elevation of MG along with declination of GSH and antioxidant
      status may be associated with free radical damage in RA.

PMID- 17454134
TI  - The effects of chelating agents on radical generation in alkaline peroxide
      systems, and the relevance to substrate damage.
AB  - A spin-trapping EPR technique has been employed to explore the generation of
      hydroxyl radicals from reactions between a series of first row transition metal
      ions and aqueous hydrogen peroxide at pH 10, and with a range of chelating agents
      (EDTA, DTPMP and the readily biodegradable ligands S,S-EDDS and IDS). In the
      absence of these chelating agents only Cu(II) generates a significant level of
      hydroxyl radicals; in their presence with Cu(II) EDTA and IDS give similar
      behaviour whereas EDDS and DTPMP inhibit hydroxyl radical generation. For Fe(II),
      EDTA, DTPMP and IDS significantly enhance ( radical)OH production under these
      conditions whereas EDDS does not. Results from model cellulose damage experiments
      broadly confirm the findings for copper, though experiments with Fe(II) lead to
      somewhat contrasting results. Our findings are discussed in terms of binding
      constants and implications for alkaline peroxygen bleaching systems.

PMID- 17454135
TI  - 15N-CIDNP investigations during tryptophan, N-acetyl-L-tryptophan, and melatonin
      nitration with reactive nitrogen species.
AB  - Tryptophan and melatonin are nitrated by peroxynitrite; tryptophan residues in
      proteins are susceptible to attack by reactive nitrogen species. Nitrated
      tryptophan might therefore be used as a biomarker for the involvement of reactive
      species derived from nitrogen oxide in a variety of pathophysiological
      conditions. The radical character of the tryptophan (Trp) and N-acetyl-L
      tryptophan (N-AcTrp) nitration with peroxynitrite is shown using (15)N-CIDNP.
      During the decay of peroxynitrite-(15)N in the presence of Trp at pH 5 in the
      probe of a (15)N-NMR spectrometer, the (15)N-NMR signals of various nitrated
      tryptophans ((15)NO(2)-Trp) show emission (E). The effects are built up in
      radical pairs [Trp( radical), 15NO2 ](F) formed by diffusive encounters of
      radicals 15NO2 and Trp( radical) generated during decay of peroxynitrite-(15)N in
      the presence of Trp. Similar (15)N-CIDNP effects are observed during reaction of
      Trp and/or N-AcTrp using the nitrating systems H(15)NO(3), H(15)NO(4) and
      H(2)O(2)/15NO2 /HRP, which are also built up in radical pairs [Trp, 15NO2 ](F).
      During nitration of melatonin (Mel) with peroxynitrite-(15)N and H(15)NO(4), the
      (15)N-NMR signal of 4-nitromelatonin (4-(15)NO(2)-Mel) shows emission arising
      from radical pairs [Mel, 15NO2 ](F) which are formed in an analogous manner.

PMID- 17454136
TI  - Oxidation-induced calcium-dependent dehydration of normal human red blood cells.
AB  - Phenazine-methosulphate (PMS) is a strong oxidant that induces reactive oxygen
      species (ROS) formation in cells. Though it has been shown that PMS increases the
      red blood cell (RBC) membrane permeability to K(+), the hypotheses on the
      mechanism of PMS-induced effects are contradictory and there are no data on
      volume changes induced by this oxidant. Therefore, the influence of the PMS +
      ascorbate oxidative system on the volume of normal human RBCs was studied. In a
      Ca(2 + )-containing medium, PMS + ascorbate caused dehydration (shrinking) of
      RBCs judged by: (1) changes in the density and osmotic resistance distributions
      of RBCs, and (2) a decrease in their low-angle scattering assessed by FACS
      analysis. The dehydration resulted from activation of the Gardos channels, was
      PMS and ascorbate concentration-dependent, was associated with broadening of the
      density and osmotic resistance distributions of the RBCs, and decreased in the
      presence of the taxifolin and rutin antioxidants. These findings contribute to a
      better understanding of the physiology and pathology of oxidatively-modified RBCs
      and may be of practical significance in estimating the antioxidant activity of
      various substances.

PMID- 17454137
TI  - Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), a reliable oxidative
      stress marker in hypertension.
AB  - The potential use of oxidative stress products as disease markers and progression
      is an important aspect of biomedical research. In the present study, the
      quantification of urine 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG)
      concentration has been used to express the oxidation status of hypertensive
      subjects. 8-oxo-dG has been simultaneously isolated and assayed in nuclear (nDNA)
      and mitochondrial DNA (mtDNA). In addition, oxidative stress of mononuclear cells
      has been estimated by means of GSH and GSSG levels and GSSG/GSH ratio in
      hypertensive subjects before and after antihypertensive treatment. It is shown
      that oxidative stress decreases significantly in hypertensive patients after
      treatment the effect being accompanied by reduction of their blood pressure. A
      significant correlation is observed comparing the yield of urine 8-oxo-dG and
      that isolated from mitochondria DNA. Moreover, urinary excretion of 8-oxo-dG also
      correlates with the GSSG/GSH ratio of cells. CONCLUSION: urine 8-oxo-dG assay is
      a good marker for monitoring oxidative stress changes in hypertensives.

PMID- 17454138
TI  - Hydrogen peroxide induces the death of astrocytes through the down-regulation of
      the constitutive nuclear factor-kappaB activity.
AB  - Nuclear factor-kappaB (NF-kappaB) has a dual role in the promotion or attenuation
      of cell death. Here, we demonstrated the role of NF-kappaB in the H(2)O(2)
      induced death of astrocytes. H(2)O(2) evoked the release of lactate dehydrogenase
      (LDH), a marker of cell death, and concomitantly decreased the DNA binding and
      transcriptional activity of NF-kappaB in cultured astrocytes. H(2)O(2)-induced
      astrocyte death was markedly increased by the co-treatment with
      pyrrolidinedithiocarbamate, an NF-kappaB inhibitor. Moreover, the elevation of
      constitutive NF-kappaB activity by overexpressing p65 NF-kappaB subunit
      attenuated H(2)O(2) toxicity, whereas NF-kappaB inhibition by overexpressing
      IkappaB potentiated the toxicity. NF-kappaB activity and H(2)O(2) cytotoxicity
      was further found to be dependent on cell density. Compared with astrocytes in
      low cell density, those in high cell density exhibited a higher constitutive NF
      kappaB activity and a stronger resistance to H(2)O(2) cytotoxicity. These results
      indicate that the constitutive activity of NF-kappaB in astrocytes is required
      for their survival under oxidative stress such as H(2)O(2).

PMID- 17454139
TI  - Does the cellular labile iron pool participate in the oxidation of 2',7'
      dichlorodihydrofluorescein?
AB  - The fluorogenic probe 2',7'-dichlorodihydrofluorescein diacetate (H(2)DCF-DA) is
      widely used for the estimation of oxidative stress in cells. It is known that
      2',7'-dichlorodihydrofluorescein (H(2)DCF), product of intracellular hydrolysis
      of H(2)DCF-DA, is oxidized to the fluorescent compound, DCF, mainly by hydrogen
      peroxide (H(2)O(2)) in the presence of catalysts. The present study was aimed at
      answering the question whether the labile iron pool (LIP) may contribute to the
      oxidation of H(2)DCF in cellular systems. The membrane-permeable lipophilic iron
      chelator salicylaldehyde isonicotinoyl hydrazone (SIH) was found to inhibit
      oxidation of the probe by H(2)O(2) dependent on ferrous ions but not by
      peroxidase or superoxide dismutase in defined in vitro systems. When applied to
      cells, the probe inhibited considerably oxidation of H(2)DCF in V79 Chinese
      hamster fibroblasts and two murine lymphoma L5178Y(LY) sublines (LY-R, LY-S)
      differing in LIP level, the extent of inhibition being greater in the LY-R line
      of higher LIP level. These results demonstrate that LIP is a significant factor
      determining the rate of intracellular H(2)DCF oxidation.

PMID- 17454140
TI  - Low oxygen tension alleviates oxidative damage and delays cellular senescence in
      G6PD-deficient cells.
AB  - Previous studies have shown that glucose-6-phosphate dehydrogenase (G6PD)
      deficient cells are under increased oxidative stress and undergo premature
      cellular senescence. The present study demonstrates that G6PD-deficient cells
      cultured under 3% oxygen concentration had an extended replicative lifespan, as
      compared with those cultured under atmospheric oxygen level. This was accompanied
      by a reduction in the number of senescence-associated beta-galactosidase (SA-beta
      Gal) positive and morphologically senile cells at comparable population doubling
      levels (PDL). Concomitant with the extension of lifespan was decreased production
      of reactive oxygen species. Additionally, lifespan extension was paralleled by
      the greatly abated formation of such oxidative damage markers as 8-hydroxy
      deoxyguanosine (8-OHdG) as well as the oxidized and cross-linked proteins.
      Moreover, the mitochondrial mass increased, but the mitochondrial membrane
      potential DeltaPsim decreased in cells upon serial propagation. These changes
      were inhibited by lowering the oxygen tension. Our findings provide additional
      support to the notion that oxidative damage contributes to replicative senescence
      of G6PD-deficient cells and reduction of oxidative damage by lowering oxygen
      tension can delay the onset of cellular senescence.

PMID- 17454141
TI  - Protection of yeast lacking the Ure2 protein against the toxicity of heavy metals
      and hydroperoxides by antioxidants.
AB  - The aim of this study was to examine the protection of the yeast lacking the
      "antioxidant-like" prion precursor protein (Ure2p), by antioxidants and to
      elucidate how modification of redox homeostasis affects toxicity of agents
      inducing oxidative stress in the Deltaure2 cells. We found a diverse ability of a
      range of antioxidants to ameliorate the hypersensitivity of the Deltaure2
      disruptant to oxidants and heavy metal ions. Glutathione and then ascorbate were
      the most effective antioxidants; Tempol, Trolox and melatonin were much less
      effective or even hampered the growth of the Deltaure2 cells exposed to tested
      agents. The intracellular level of ROS was augmented in the Deltaure2 mutant
      under normal growth conditions (1.7-fold), and after treatment with H(2)O(2) (2.3
      fold) and Cd(II) (2.8-fold), with respect to its wild-type counterpart.
      Glutathione was unable to prevent the increase in ROS production caused by
      CdCl(2). The Deltaure2 disruptant was also hypersensitive to heat shock, like
      mutants lacking glutathione S-transferases.

PMID- 17454142
TI  - 4-HPR-mediated leukemia cell cytotoxicity is triggered by ceramide-induced
      mitochondrial oxidative stress and is regulated downstream by Bcl-2.
AB  - We have previously reported that, in leukemia cells, the cytotoxicity of the
      anticancer agent N-(4-hydroxyphenyl)retinamide (4-HPR) is mediated by
      mitochondria-derived reactive oxygen species (ROS) and cardiolipin peroxidation.
      Here, we have analyzed at greater depth the 4-HPR-triggered molecular events,
      demonstrating that 4-HPR induces an early (15 min) increase in ceramide levels by
      sphingomyelin hydrolysis and later (from 1 h) by de novo synthesis. Using
      specific inhibitors of both pathways, we demonstrate that ceramide accumulation
      is responsible for early ROS generation, which act as apoptotic signalling
      intermediates leading to conformational activation of Bak and Bax, loss of
      mitochondrial membrane potential (DeltaPsim), mitochondrial membrane
      permeabilization (MMP) and cell death. Enforced expression of Bcl-2 has no effect
      on 4-HPR-induced oxidative stress, but notably prevents mitochondrial alterations
      and apoptosis, indicating that Bcl-2 functions by regulating events downstream of
      ROS generation. In conclusion, our study delineates for the fist time the
      sequence and timing of the principal events induced by 4-HPR in leukemia cells
      and points to the potential use of modulators of ceramide metabolism as enhancers
      in 4-HPR-based therapies.

PMID- 17454143
TI  - [6]-Gingerol prevents UVB-induced ROS production and COX-2 expression in vitro
      and in vivo.
AB  - [6]-Gingerol, a naturally occurring plant phenol, is one of the major components
      of fresh ginger (Zingiber officinale Roscoe, Zingiberaceae) and has diverse
      pharmacologic effects. Here, we describe its novel anti-oxidant, anti-apoptotic,
      and anti-inflammatory activities in vitro and in vivo. In vitro, pre-treatment
      with [6]-gingerol reduced UVB-induced intracellular reactive oxygen species
      levels, activation of caspase-3, -8, -9, and Fas expression. It also reduced UVB
      induced expression and transactivation of COX-2. Translocation of NF-kappaB from
      cytosol to nucleus in HaCaT cells was inhibited by [6]-gingerol via suppression
      of IkappaBalpha phosphorylation (ser-32). Examination by EMSAs and
      immunohistochemistry showed that topical application of [6]-gingerol (30 microM)
      prior to UVB irradiation (5 kJ/m(2)) of hairless mice, also inhibited the
      induction of COX-2 mRNA and protein, as well as NF-kappaB translocation. These
      results suggest that [6]-gingerol could be an effective therapeutic agent
      providing protection against UVB-induced skin disorders.

PMID- 17454144
TI  - Comparison of three approaches for inhibiting insulin-like growth factor I
      receptor and their effects on NSCLC cell lines in vitro.
AB  - The insulin-like growth factor-1 receptor (IGF-1R) mitogenic signaling mediates
      malignant cell survival by many complex and redundant pathways. This study
      compared the effects of IGF-1R inhibition on viability and apoptosis of two NSCLC
      cell lines, using three different methods for the impairment of IGF-1R function:
      (IR3, an anti-IGF-1R antibody; tyrphostin AG1024, a tyrosine kinase inhibitor
      (TKI) and IGF-1R-small interfering RNA (siRNA). IGF-1R inhibition led to a
      decrease of cell survival and induced apoptosis in a manner depending on the
      approach used for the receptor inhibition. To find an explanation, we analyzed
      the effects of these treatments on three major antiapoptotic pathways evoked by
      IGF-1R signaling: IRS-1, Shc and 14.3.3-dependent mitochondrial translocation of
      Raf-1 kinase (mitRaf). (IR3 downregulated IRS-1 phosphorylation in A549 cells and
      Shc phosphorylation in U1810 cells. While in A549 cells AG1024 treatment
      decreased both IRS-1 and Shc phosphorylation, in U1810 cells the IRS-1
      phosphorylation was only slightly affected and the Shc phosphorylation
      drastically downregulated. Neither (IR3 nor AG1024 had any effect on Raf-1 kinase
      translocation. Irrespective of the cell line, IGF-1R-siRNA treatment induced
      downregulation of both IRS-1 and Shc phosphorylation coupled with the abrogation
      of mitRaf. In addition, the IGF-1R-siRNA proved to be the most potent inducer of
      apoptosis suggesting that more than one antiapoptotic pathway in IGF-1R signaling
      should be inhibited to effectively induce apoptosis in lung cancer cells.

PMID- 17454145
TI  - Effects of short-term physical training on the liver IGF-I in diabetic rats.
AB  - To investigate the influence of short-term physical training on IGF-I
      concentrations in diabetic rats, male wistar rats were distributed into four
      groups: sedentary control, trained control, sedentary diabetic and trained
      diabetic. Diabetes was induced by Alloxan (32 mg/kg b.w.) and training protocol
      consisted of swimming 1 h/day, 5 days/week, during 4 weeks, supporting 5% b.w. At
      the end of this period, rats were sacrificed and blood was collected for
      determinations of serum glucose, insulin, albumin, IGF-I and hematocrit. Liver
      samples were used to determine glycogen, protein, DNA and IGF-I concentrations.
      Diabetes reduced insulin and IGF-I concentrations in blood and liver protein,
      ratio protein/DNA and IGF-I concentrations in liver and increased glycemia.
      Physical training reduced serum glucose and recovered hepatic glycogen stores in
      diabetic rats and reduced serum and liver IGF-I concentrations. In conclusion,
      short-term physical training improved the metabolic conditions of diabetic rats,
      despite of impairing liver and blood IGF-I concentrations.

PMID- 17454146
TI  - Prognostic value of platelet-derived growth factor in patients with severe
      sepsis.
AB  - PRIMARY OBJECTIVE: Platelet-derived growth factor-BB (PDGF-BB) has been shown to
      promote the structural integrity of the vessel wall and to increase wound healing
      capacity. Aim of the present study was to determine the role of PDGF-BB in the
      context of outcome of septic patients. Furthermore, the effect of treatment with
      recombinant human activated protein C (rhAPC) on plasma levels of PDGF-BB in
      severe sepsis was evaluated as well as the in vitro effect of rhAPC on PDGF-BB
      release from human endothelial cells (HUVEC). RESEARCH DESIGN, METHODS AND
      PROCEDURES: PDGF-BB levels were measured in 46 patients on day 3 of severe
      sepsis. Twenty-one of these patients received treatment with rhAPC. The in vitro
      effect of rhAPC on PDGF-BB-messenger RNA synthesis and release of PDGF-BB into
      supernatants was measured by reverse transcriptase-polymerase chain reaction and
      ELISA-methods. MAIN OUTCOMES AND RESULTS: Survivors of severe sepsis presented
      with higher PDGF-BB levels than non-survivors (p < 0.05). Septic patients with
      PDGF-BB levels below 200 pg/ml were 7.3 times more likely (RR = 7.3, 95% CI: 1.4
      44.5; p < 0.05) to die from sepsis than patients with higher PDGF-BB values.
      RhAPC (1-10 microg/ml) stimulated endothelial PDGF-BB-messenger RNA transcription
      and PDGF-BB-release in vitro. Plasma levels of PDGF-BB in patients receiving
      rhAPC were significantly (p < 0.01) higher (median 277.7; 25-75th percentiles:
      150.5-414.4 pg/ml) than in patients not treated with rhAPC (median: 125.6; 25
      75th percentiles: 55.3-344.7 pg/ml). CONCLUSIONS: The ability of rhAPC to
      upregulate endothelial PDGF-BB production may represent a new molecular mechanism
      by which rhAPC controls vessel wall homeostasis and increases tissue healing
      capacity in severe sepsis. PDGF-BB may serve as useful laboratory marker to
      predict survival in patients presenting with severe sepsis.

PMID- 17454147
TI  - Wnt1 and Wnt5a affect endothelial proliferation and capillary length; Wnt2 does
      not.
AB  - Blood vessel growth is critical for embryonic development and contributes to
      pathologies including cancer and diabetic retinopathy. A growing body of evidence
      suggests that signaling via the Wnt/beta-catenin pathway contributes to
      angiogenesis, and that paracrine Wnt signaling might alter endothelial cell
      function. To test the hypothesis that Wnt signaling promotes endothelial cell
      proliferation and vessel growth, we treated bovine aortic endothelial cells with
      Wnt1, Wnt2 and Wnt5a derived from coculture with Wnt-expressing fibroblasts.
      Endothelial cells cultured in the presence of Wnt1 displayed increased Wnt/beta
      catenin signaling, proliferation and capillary stability in vitro. Wnt5a, which
      primarily signals via an alternate Wnt pathway, the Wnt/Ca(++) pathway, decreased
      both cell number and capillary length. Wnt2, which in other cell types activates
      the Wnt/beta-catenin pathway, did not activate signaling, affect cell number or
      increase capillary length. These results suggest that Wnt/beta-catenin and
      Wnt/Ca(++) signals might have opposing effects on angiogenesis.

PMID- 17454148
TI  - An in vitro model for assessment of the biological activity of hepatocyte growth
      factor.
AB  - Hepatocyte growth factor (HGF) is a multifunctional growth factor with potent
      wound-healing properties that functions in the healing of chronic injuries.
      However, there may be a loss of HGF activity in certain chronic cases; this might
      be indicated by the presence of high amounts of HGF in body fluids and by the
      elevated expression of the HGF receptor in tissue biopsies. In such cases, a
      reliable means of assessing the activity of endogenous HGF would be valuable in
      allowing clinicians to decide if treatment with HGF would be useful. In this
      study, we developed an in vitro wound assay that used a mouse skin epithelial
      cell line to evaluate the biological activity of HGF. We showed that HGF
      accelerated the motility of the epithelial cells in a dose-dependent fashion with
      high sensitivity and specificity. This in vitro assay might be used to determine
      the activity of both endogenous and recombinant HGF.

PMID- 17454149
TI  - Papillary thyroid carcinoma with lymph node metastases.
AB  - Papillary thyroid cancer (PTC) is the most frequently occurring human thyroid
      cancer with good prognosis following appropriate treatment. Lymph node (LN)
      metastases are the main way through which PTC spread cancer cells. The mechanisms
      underlying PTC with local invasion, LN metastases and distant metastases are not
      well investigated. Tumor secrete cytokines, such as vascular endothelial growth
      factor (VEGF)-C and -D bind to VEGF receptors on lymphatic endothelial cells and
      induce proliferation (budding) from nearby lymphatic capillaries and growth of
      new lymphatic capillaries. About one-third of patients can be diagnosed at the
      time of surgical findings. Different image studies, such as ultrasonography with
      fine needle aspiration cytology, scintigraphic localization and positron emission
      tomography were reported to detect LN metastases. Important factors in predicting
      LN metastases are vascular invasion, male gender, absence of tumor capsule, and
      perithyroid involvement. Tumor recurrence in LN after primary treatment of PTC
      had an independent and highly significant negative effect on survival in patients
      over 45 year-old. Recombinant adeno-associated virus-mediated gene transfer of
      sVEGFR3-Fc is a feasible therapeutic scheme for blocking lymphogenous metastasis.
      In conclusion, aggressive surgical procedures performed by experienced surgeons
      or postoperative radioactive iodine therapy to minimize local recurrence of LN
      for PTC patients with high risk.

PMID- 17454150
TI  - Glycosaminoglycan synthesis and shedding induced by growth factors are cell and
      compound specific.
AB  - The interactions between growth factors and sulphated glycosaminoglycans (GAG)
      have been extensively studied. The aim of this study is to investigate if growth
      factors would show specificity of action on the synthesis and shedding of
      sulphated GAG, using two different cell lines: endothelial and smooth muscle
      cells. The cells were grown in the presence or absence of growth factors: EGF,
      FGF2, VEGF121, VEGF165. Transfection assays were also performed using recombinant
      pcDNA3.1, containing VEGF165 cDNA. In order to analyse the different types of GAG
      the cells were metabolically labelled with [(35)S]-sulphate. At low doses,
      VEGF121 was the only growth factor able to increase both the synthesis and
      secretion of heparan sulphate (HS) in endothelial cells. Over expression of
      VEGF165 stimulated HS synthesis in both cells. The combined results showed that
      growth factors affect GAG synthesis in a cell specific and dose dependent manner.

PMID- 17454151
TI  - Antimicrobial peptides derived from growth factors.
AB  - Growth factors, comprising diverse protein and peptide families, are involved in
      a multitude of developmental processes, including embryogenesis, angiogenesis,
      and wound healing. Here we show that peptides derived from HB-EGF, amphiregulin,
      hepatocyte growth factor, PDGF-A and PDGF-B, as well as various FGFs are
      antimicrobial, demonstrating a previously unknown activity of growth factor
      derived peptides. The peptides killed the Gram-negative bacteria Escherichia
      coli, Pseudomonas aeruginosa, and the Gram-positive Bacillus subtilis, as well as
      the fungus Candida albicans. Several peptides were also active against the Gram
      positive S. aureus. Electron microscopy analysis of peptide-treated bacteria,
      paired with analysis of peptide effects on liposomes, showed that the peptides
      exerted membrane-breaking effects similar to those seen after treatment with the
      "classical" human antimicrobial peptide LL-37. Furthermore, HB-EGF was
      antibacterial per se, and its epitope GKRKKKGKGLGKKRDPCLRKYK retained its
      activity in presence of physiological salt and plasma. No discernible hemolysis
      was noted for the growth factor-derived peptides. Besides providing novel
      templates for design of peptide-based antimicrobials, our findings demonstrate a
      previously undisclosed link between the family of growth factors and
      antimicrobial peptides, both of which are induced during tissue remodelling and
      repair.

PMID- 17454152
TI  - Why are estrogens rarely used for the treatment of depression in women?

PMID- 17454153
TI  - Subclinical hyperthyroidism as a potential factor for dysfunctional uterine
      bleeding.
AB  - OBJECTIVE: To evaluate the functional status of the thyroid gland in apparently
      euthyroid women with dysfunctional uterine bleeding. MATERIALS AND METHODS: Forty
      apparently euthyroid women with menorrhagia and no pathologic lesion in the
      genital tract were compared with 20 women having normal menstrual cycles as
      controls. All women underwent hormonal evaluation: serum total and free
      triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH) and
      serum prolactin. RESULTS: Statistically significant differences were observed in
      the values of TSH, total T3, free T3, free T4 and total T4 between the
      menorrhagia and the control group. Prolactin was increased significantly in the
      menorrhagia group. CONCLUSION: Subclinical hyperthyroidism can be a potential
      risk factor for dysfunctional uterine bleeding. Other studies are needed to
      confirm our findings.

PMID- 17454154
TI  - Hypothyroidism and hyperlipidemia with a virilizing ovarian steroid cell tumor,
      not otherwise specified.
AB  - Steroid cell tumors, not otherwise specified, are rare ovarian sex cord-stromal
      tumors with malignant potential. The majority of these tumors produce steroids,
      with testosterone being the most common. A 44-year-old woman with hypothyroidism
      and hyperlipidemia presented with abrupt onset of oligomenorrhea, progressive
      virilization as acne, hirsutism and clitoromegaly, and a non-palpable pelvic
      mass. The preoperatively elevated serum testosterone level returned to normal
      after salpingo-oophorectomy, and then menstrual flow became regular.

PMID- 17454155
TI  - The influence of estradiol/follicle and estradiol/oocyte ratios on the outcome of
      controlled ovarian stimulation for in vitro fertilization.
AB  - OBJECTIVE: The aim of the study was to evaluate the influence of the ratios of
      estradiol (E2) to either the number of follicles >14 mm on the day of human
      chorionic gonadotropin administration (E2/follicle) or the number of oocytes
      retrieved (E2/oocytes) during controlled ovarian hyperstimulation (COH) with
      gonadotropin-releasing hormone (GnRH)-agonist (agonist group) and GnRH-antagonist
      (antagonist group), on the outcome of in vitro fertilization (IVF) cycles.
      PATIENTS AND METHODS: All consecutive women aged <35 years admitted to our IVF
      unit during a 6-year period with normal to high response to COH were
      retrospectively studied. Ovarian stimulation characteristics, number of oocytes
      retrieved, number of embryos transferred and pregnancy rate were assessed.
      RESULTS: Six hundred and ninety consecutive IVF cycles were evaluated, 301 in the
      agonist group and 389 in the antagonist group. The ratios of E2/follicle and
      E2/oocyte were significantly higher in the agonist group (p < 0.001 for both).
      Moreover, while pregnancy rates within E2/oocyte ratio of 100-200 pg/ml were
      comparable between the agonist and antagonist groups, when E2/oocyte ratios were
      <100 pg/ml or >200 pg/ml, pregnancy rates were significantly higher in the
      agonist group. Furthermore, no difference in pregnancy rates was observed within
      the agonist group between different E2/oocytes ratios, while within the
      antagonist group, higher pregnancy rates were observed when comparing those with
      E2/oocyte ratio of 100-200 pg/ml with those with E2/oocyte ratio <100 pg/ml or
      >200 pg/ml. CONCLUSION: While E2/oocyte ratio cannot predict the success of GnRH
      agonist protocol, patients undergoing GnRH-antagonist protocol should reach
      E2/oocyte ratio within the 100-200 pg/ml range in order to achieve the best IVF
      outcome.

PMID- 17454156
TI  - A randomized comparison of ovulation induction and hormone profile between the
      aromatase inhibitor anastrozole and clomiphene citrate in women with infertility.
AB  - BACKGROUND: IN the present study we evaluated and compared the effects of
      ovulation and hormonal dynamics induced by anastrozole and clomiphene citrate in
      women with infertility. MATERIALS AND METHODS: Thirty-three infertile patients,
      aged 25-41 years, were enrolled. Patients received either anastrozole 1 mg daily
      (AI group) or clomiphene citrate 100 mg daily (CC group) from cycle day 3 to day
      7. Number of mature follicles (> or =18 mm), endometrial thickness, pregnancy
      rate and serial hormone profiles (follicle-stimulating hormone (FSH), luteinizing
      hormone (LH), estradiol (E(2)), testosterone and progesterone) were measured on
      cycle day 3, day 8, day 10, the day of intrauterine insemination (IUI), day 7
      after IUI and day 14 after IUI. RESULTS: Baseline parameters were similar in the
      two groups, including age, body mass index, infertility duration and day-3 serum
      hormones except FSH. The mean FSH value on day 3 was significantly different (4.3
      mIU/ml in the AI group vs. 6.3 mIU/ml in the CC group; p < 0.05). The women
      receiving anastrozole had fewer ovulatory follicles (1.2 in the AI group vs. 1.8
      in the CC group; p < 0.05) and a thicker endometrium (10.6 mm in the AI group vs.
      7.8 mm in the CC group; p < 0.05). The levels of progesterone and testosterone
      were similar during ovulation stimulation cycles in both groups. On the other
      hand, the AI group had a significantly higher LH level but a significantly lower
      E(2) level in the stimulation cycle. CONCLUSION: Anastrozole has a high pregnancy
      rate, although it induces fewer ovulatory follicles compared with clomiphene
      citrate. The two drugs gave different responses of FSH, LH and E2 during
      stimulation cycles.

PMID- 17454157
TI  - Ovulation induction in a poor responder with panhypopituitarism: a case report
      and review of the literature.
AB  - BACKGROUND: Most women with panhypopituitarism will undergo successful ovulation
      induction with gonadotropin therapy. Few proven treatment options exist for those
      who respond poorly to such therapy. A poor response may indicate diminished
      ovarian reserve, or reflect a deficiency of other key components for ovarian
      function. CASE: A 31-year-old female with panhypopituitarism and a poor response
      to gonadotropin therapy took growth hormone (GH) replacement for 4 months prior
      to restarting gonadotropins. When the serum level of insulin-like growth factor-I
      normalized, she began ovulation induction with gonadotropins with transdermal
      estradiol. After 63 days of gonadotropin therapy, she had a leading follicle of
      18 mm, followed by follicles of 16.5 mm and 15.5 mm. The serum estradiol was 796
      pg/ml, and human chorionic gonadotropin was administered. The patient conceived
      with timed intercourse. A prior attempt at ovulation induction with gonadotropins
      alone failed to produce follicular development. CONCLUSION: Prolonged
      gonadotropin treatment may be necessary to achieve ovulation and avoid the
      misdiagnosis of ovarian failure. Co-treatment with GH and estrogen may improve
      the follicular response in a poor responder with panhypopituitarism.

PMID- 17454158
TI  - Ovarian tissue preservation, present and clinical perspectives.
AB  - Ovarian tissue preservation and transplantation are intended for women undergoing
      aggressive regimens of chemical and/or radiological therapy, bone marrow
      transplantation or stem cell transplantation. Main indications for the procedure
      are neoplastic diseases and autoimmune disorders. The first live human birth
      after ovarian tissue autotransplantation was successfully done in 2002.
      Cryopreserved ovarian tissue can be autografted either orthotopically or
      heterotopically. Neovascularization of the implanted tissue is essential for the
      procedure. Vascular transplantation seems to be the best approach for avoiding
      follicular loss and extending the lifespan of the ovarian grafts. The procedure,
      regardless of whether ortho- or heterotopic, is connected with a risk of
      reimplantation of neoplastic cells. This can be minimized by multiple ovary
      biopsies, thorough histological examination and molecular genetic techniques.
      Introducing ovarian tissue transplantation into clinical practice requires many
      problems to be solved. Standardization of the freeze-thaw protocol is one of the
      most important issues. Solving the problem of transient graft ischemia is also
      essential. Eventually, the future safety of the method requires the development
      of efficient tests to detect the presence of neoplastic cells in the transplanted
      tissue.

PMID- 17454159
TI  - 17-Hydroxyprogesterone deficiency as a cause of sexual infantilism and arterial
      hypertension: laboratory and molecular diagnosis--a case report.
AB  - The differential diagnosis of hypertension associated with hypokalemia in infancy
      and adolescence should necessarily include deficiency of the 17alpha-hydroxylase
      enzyme, a rare form of congenital adrenal hyperplasia (CAH). In addition to
      hypertension, the classic syndrome caused by this deficiency is characterized by
      suppressed production of sex hormones and consequently sexual infantilism.
      Although rare (1% of all forms of CAH), there appears to be a higher incidence of
      this syndrome in some population groups. This is a case report on two sisters
      followed up at the Department of Obstetrics and Gynecology, School of Medicine,
      Universidade Estadual de Campinas (UNICAMP), who were both found to have the
      46,XY genotype with homozygosis for W406R, exon 7 of the CYP17 gene (OMIM
      202110). The condition was diagnosed only at puberty when hypergonadotropic
      hypogonadism resulted in sexual infantilism; however, arterial hypertension had
      been present since infancy and late diagnosis and lack of timely adequate
      treatment resulted in complications.

PMID- 17454160
TI  - Effects of postmenopausal hormone replacement therapy on body fat composition.
AB  - AIM: To evaluate the effects of different types, regimens and administration
      routes of hormone replacement therapy (HRT) on body fat composition indices in
      postmenopausal women at increased risk of anthropometry-related cardiovascular
      disease (CVD). METHODS: Fifty-nine postmenopausal women (aged 41-57 years, mean
      +/- standard deviation: 49.9 +/- 3.8 years) with body mass index (BMI) > or =25
      kg/m(2) participated in this 6-month, prospective, randomized single-blind study.
      Subjects were assigned into three groups and received transdermal estradiol
      (E2)/norethisterone acetate (NETA) (50 microg E2 daily for 14 days followed by 50
      microg E2/0.25 microg NETA daily for 14 days; transdermal group, n = 19),
      transdermal continuous E2/oral medroxyprogesterone acetate (MPA) (50 microg E2/5
      mg MPA daily; transdermal/oral group, n = 19) or oral continuous E2/NETA (1 mg
      E2/0.5 mg NETA daily; oral group, n = 21). Anthropometric indices (body weight,
      height, and hip and waist circumferences) were measured, and BMI and waist-to-hip
      ratio (WHR) were calculated, before and after treatment. Also, the thickness of
      subcutaneous abdominal fat was measured by ultrasound. Depending on waist
      circumference (WC), the subjects were divided into two risk groups: increased
      risk group with WC <88 cm (n = 32) and high-risk group with WC > or =88 cm (n =
      27). Also, the effects of HRT were evaluated separately in subjects with median
      subcutaneous fat of <33 mm (n = 29) and those with median subcutaneous fat of >
      or =33 mm (n = 30). RESULTS: Overall, all three types of HRT caused a significant
      decrease in both WC and subcutaneous fat (p < 0.001), and also in WHR (p < 0.05).
      There was no significant difference in baseline (p > 0.05) and final values (p >
      0.05) between HRT groups. In each group, all types of HRT significantly decreased
      WC and subcutaneous fat (transdermal group: p < 0.001 and p < 0.05;
      transdermal/oral group: p < 0.001 and p < 0.01; oral group: p < 0.001 and p <
      0.001, respectively), while body weight, BMI and WHR changed only insignificantly
      (p > 0.05). In the increased-risk group, body weight increased significantly (p <
      0.05) while WC and subcutaneous fat decreased significantly (p < 0.001 and p <
      0.001). As for the high-risk group, there was a significant decrease in WC and
      subcutaneous fat (p < 0.001, p < 0.001) while the remaining parameters did not
      change significantly. However, BMI showed a tendency to increase in the increased
      risk group, while there was a decrease in all measurements in the high-risk
      group. Regardless of the drugs used and baseline subcutaneous fat, WC and
      subcutaneous fat decreased significantly at the end of the treatment
      (subcutaneous fat <33 mm: p < 0.001 and p < 0.01; subcutaneous fat > or =33 mm: p
      < 0.001 and p < 0.001, respectively). CONCLUSIONS: The three different types of
      HRT have comparable effects on central fat tissue in women at increased risk of
      anthropometry-related CVD. Indeed, the three combinations of HRT reduced fat
      tissue in the central part of the body. However, the overall effect of HRT was
      more marked in women with WC > or =88 cm and subcutaneous fat > or =33 cm.
      Whether HRT increases body weight depends on the body composition indices of
      individuals before treatment.

PMID- 17454161
TI  - Expression analysis of the genes involved in estradiol and progesterone action in
      human ovarian endometriosis.
AB  - Endometriosis is defined as the presence of endometrial glands and stroma within
      extrauterine sites, and it is well known that endometriosis is an estrogen
      dependent disease. The defective formation and metabolism of steroid hormones is
      responsible for the promotion and development of endometriosis. In the present
      study we examined the mRNA levels of six enzymes that are involved in the
      metabolism of estrogen and progesterone--aromatase, 17beta-hydroxysteroid
      dehydrogenase (17beta-HSD) types 1, 2 and 7, sulfatase and sulfotransferase--and
      of the steroid receptors--estrogen receptors alpha and beta (ERalpha, ERbeta) and
      progesterone receptors A and B (PRAB)--implicated in human ovarian endometriosis.
      We analyzed 16 samples of ovarian endometriosis and 9 of normal endometrium. The
      real-time polymerase chain reaction analyses revealed that six of the nine genes
      investigated are differentially regulated. Aromatase, 17beta-HSD types 1 and 7,
      sulfatase and ERbeta were statistically significantly upregulated, while ERalpha
      was significantly downregulated, in the endometriosis group compared with the
      control group. There were no significant differences in 17beta-HSD type 2,
      sulfotransferase and PRAB gene expression. Our results indicate that, in addition
      to the previously reported upregulation of aromatase, upregulation of 17beta-HSD
      types 1 and 7 and sulfatase can also increase the local estradiol concentration.
      This could thus be responsible for the estrogen-dependent growth of endometriotic
      tissue. Surprisingly ERalpha was downregulated.

PMID- 17454162
TI  - Low leptin level in an obese hyperandrogenic woman--potential marker for androgen
      secreting tumor.
AB  - Hyperandrogenism in postmenopausal women is due to ovarian hyperthecosis or an
      androgen-secreting ovarian/adrenal tumor. Making the correct diagnosis might be
      complicated due to the possible existence of an adrenal neoplasm secreting
      testosterone only, ectopic ovarian tissue or ectopic luteinizing hormone/human
      chorionic gonadotropin receptors in the adrenals, as well as the relatively low
      sensitivity of imaging techniques (computed tomography, magnetic resonance
      imaging) and vein catheterization for this type of pathology. We present the case
      of an obese postmenopausal woman with metabolic syndrome, hyperandrogenism (high
      testosterone levels, suppressed gonadotropins), adrenal macronodular hyperplasia
      and Leydig-cell ovarian tumor. At presentation she had low leptin levels despite
      high body fat content. After a catheter study left adrenalectomy was carried out
      but hyperandrogenism persisted. Then, bilateral oophorectomy with hysterectomy
      was performed and a small Leydig-cell tumor was found in the left ovary.
      Postoperatively, testosterone and gonadotropin levels were normal
      (postmenopausal) and leptin level became elevated without change in body mass
      index or body fat content. In conclusion, we speculate that low leptin levels in
      obese hyperandrogenic women might be a marker for androgen-secreting tumors.

PMID- 17454163
TI  - Phyto-Female Complex for the relief of hot flushes, night sweats and quality of
      sleep: randomized, controlled, double-blind pilot study.
AB  - OBJECTIVE: To determine the efficacy and safety of the herbal formula Phyto
      Female Complex (SupHerb, Netanya, Israel; ingredients: standardized extracts of
      black cohosh, dong quai, milk thistle, red clover, American ginseng, chaste-tree
      berry) for the relief of menopausal symptoms. METHODS: A randomized, double
      blind, placebo-controlled trial in 50 healthy pre and postmenopausal women, aged
      44-65 years, to whom oral Phyto-Female Complex or matched placebo was prescribed
      twice daily for 3 months. A structured questionnaire on the frequency and
      intensity of menopausal symptoms was administered weekly from one week before
      throughout the 3-month treatment period, followed by biochemical tests, breast
      check, and transvaginal ultrasonography. RESULTS: The women receiving Phyto
      Female Complex reported a significantly superior mean reduction in menopausal
      symptoms than the placebo group. The effect of treatment improvements in
      menopausal symptoms increased over time; by 3 months there was a 73% decrease in
      hot flushes and a 69% reduction of night sweats, accompanied by a decrease in
      their intensity and a significant benefit in terms of sleep quality. Hot flushes
      ceased completely in 47% of women in the study group compared with only 19% in
      the placebo group. There were no changes in findings on vaginal ultrasonography
      or levels of relevant hormones (estradiol, follicle-stimulating hormone), liver
      enzymes or thyroid-stimulating hormone in either group. CONCLUSION: Phyto-Female
      Complex is safe and effective for the relief of hot flushes and sleep
      disturbances in pre- and postmenopausal women, at least for 3 months' use.

PMID- 17454164
TI  - Clinical diagnostic criteria for premenstrual syndrome and guidelines for their
      quantification for research studies.
AB  - Premenstrual syndrome (PMS) encompasses a variety of symptoms appearing during
      the luteal phase of the menstrual cycle. Although PMS is widely recognized, the
      etiology remains unclear and it lacks definitive, universally accepted diagnostic
      criteria. To address these issues an international multidisciplinary group of
      experts evaluated the current definitions and diagnostic criteria of PMS and
      premenstrual dysphoric disorder (PMDD). Following extensive correspondence, a
      consensus meeting was held with the aim of producing updated diagnostic criteria
      for PMS and guidelines for clinical and research applications. This report
      presents the conclusions and recommendations of the group. It is hoped that the
      criteria proposed by the group will become widely accepted and eventually be
      incorporated into the next edition of the World Health Organization's
      International Classification of Diseases (ICD-11). It is also hoped that the
      proposed guidelines for quantification of criteria will be used by clinicians and
      investigators to facilitate diagnostic uniformity in the field as well as
      adequate treatment modalities when warranted.

PMID- 17454165
TI  - Non-genomic effects of 17beta-estradiol in activation of the ERK1/ERK2 pathway
      induces cell proliferation through upregulation of cyclin D1 expression in bovine
      artery endothelial cells.
AB  - OBJECTIVE: Growing evidence indicates that estrogen's non-genomic effects play
      important roles in cellular functions and backs up the hypothesis of the
      existence of a membrane estrogen receptor (mER) in a number of cell types, but
      little is known about the complementary effects between traditional genomic and
      novel non-genomic effects of estrogen. The aim of the present study was to
      explore the non-genomic activation of ERK1/2 mitogen-activated protein kinase
      (MAPK) by 17beta-estradiol (E(2)) through mER and its role in cell proliferation.
      METHODS: On cultured bovine artery endothelial cells (BAECs) we used the
      [(3)H]thymidine incorporation assay to evaluate the influence of E(2) on cell
      proliferation and fluorescence microscopy to show the presence of mER on the cell
      membrane. Scatchard analysis was performed to identify and characterize the mER
      on a purified membrane fraction of BAECs. RESULTS: E(2) upregulated cyclin D1
      protein expression and enhanced cell proliferation. Inhibition of the MAPK
      cascade with PD98059 or of G protein with pertussis toxin (PTX) completely
      abolished the above effects, while the estrogen receptor antagonist tamoxifen
      attenuated E(2)-dependent upregulation of cyclin D1 and cell proliferation.
      Accordingly, E(2) rapidly led to ERK1/ERK2 activation, which was prevented by
      tamoxifen or PTX and was entirely reproduced by membrane-impermeable estradiol
      bovine serum albumin conjugate (E(2)coBSA). Immunofluorescent staining with
      E(2)coBSA-fluorescein isothiocyanate resulted in a punctuate staining pattern of
      the plasma membrane and Scatchard analysis of the E(2)-binding protein in a
      purified membrane fraction of BAECs showed that E(2) binds to the membrane
      fraction with a dissociation constant of 0.2394 nmol/l. CONCLUSION: Our findings
      showed that E(2) induces cell proliferation through upregulation of cyclin D1 via
      non-genomic activation of the ERK1/ERK2 pathway mediated by mER and G protein.

PMID- 17454166
TI  - Prospective evaluation of pregnant women with hypothyroidism: implications for
      treatment.
AB  - Pregnancy is characterized by a series of maternal hormonal and metabolic changes
      which can affect thyroid function and the course of thyroid dysfunction in
      different ways. Moreover, hypothyroidism is also associated with obstetric
      complications and morbidity to the fetus. The aim of the present study was to
      evaluate the influence of hypothyroidism during the course of pregnancy and the
      necessity of adjusting the dose of levothyroxine. We prospectively followed 16
      patients with previous diagnosis of hypothyroidism. In ten patients (62.5%) it
      was necessary to raise the dose of levothyroxine, with a median increase of
      20.7%. One pregnancy was complicated by premature amniorrhexis and two by pre
      eclampsia. The screening for congenital hypothyroidism was negative in all
      newborns. We conclude that it is very important to offer screening to high-risk
      patients who wish to become pregnant. Dose adjustment based on serum levels of
      thyroid-stimulating hormone (TSH) is essential. In patients in whom TSH is not
      measured during the first weeks of pregnancy, a good approach could be to
      increase the dose of replacement therapy by 20-25% to avoid hypothyroidism.

PMID- 17454167
TI  - Effect of finasteride 5 mg (Proscar) on acne and alopecia in female patients with
      normal serum levels of free testosterone.
AB  - BACKGROUND: In some women with acne or alopecia who have normal serum levels of
      free testosterone, no clinical improvement can be reached by the classical
      treatment with antiandrogens, isotretinoids or corticosteroids. Our hypothesis is
      that some of these women have an excessive activity of the enzyme 5alpha
      reductase. OBJECTIVE: To evaluate the subjective benefit of the treatment with
      finasteride (5 mg/day) in women with normal serum levels of free testosterone
      suffering from acne or alopecia. DESIGN: This was a retrospective study
      evaluating a questionnaire filled out by 12 patients, six of whom had acne and
      six of whom had alopecia. RESULTS: Nine of the 12 patients benefited from the
      treatment, their symptoms decreased significantly and they felt better
      psychologically than before the administration of finasteride. The other three
      patients did not benefit at all from finasteride and reported no change in the
      extent of the acne/alopecia. Treatment was generally well tolerated, only a few
      adverse effects were noted. CONCLUSIONS: Nine of the 12 patients benefited from
      the treatment. This supports our hypothesis of an excessive activity of 5alpha
      reductase enzyme in peripheral tissue in these patients. The fact that three of
      the patients did not realize any change in their symptom severity implies that
      there must also be other pathways in the genesis of acne and alopecia in women
      with normal levels of free testosterone. Further evaluation is needed to
      elucidate more precise indications for the administration of finasteride in women
      with acne and alopecia.

PMID- 17454168
TI  - Metformin administration is more effective when non-obese patients with
      polycystic ovary syndrome show both hyperandrogenism and hyperinsulinemia.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disease that
      is frequently observed to be related to increased insulin resistance independent
      of body weight. The use of insulin-sensitizer compounds, such as metformin,
      permits great improvement of such metabolic abnormality, restoring ovarian
      function and gonadal steroid synthesis and reducing insulin resistance. AIM: On
      this basis we aimed to evaluate a group of non-obese amenorrheic PCOS patients
      before and after 6 months of metformin administration (500 mg orally twice daily)
      to better understand upon which basis of clinical and endocrine parameters
      metformin administration might be chosen as a putative therapeutic tool. METHOD:
      A group of non-obese PCOS patients (n = 42) was enrolled after informed consent.
      They underwent an oral glucose tolerance test for insulin, glucose and C-peptide
      levels and provided blood samples for determination of plasma levels of
      luteinizing hormone (LH), follicle-stimulating hormone, prolactin, estradiol,
      androstenedione, 17-hydroxyprogesterone, insulin, cortisol and testosterone
      levels on two occasions: before and on day 7 of the first menstrual cycle
      occurring after the 5th month of treatment. RESULTS: Plasma LH, estradiol,
      insulin and C-peptide were decreased significantly by metformin treatment in the
      entire group of PCOS patients. When subdividing PCOS patients according to
      insulin sensitivity (i.e. hyper- and normoinsulinemic subjects), a greater rate
      of positive endocrine changes was observed in hyperinsulinemic patients and the
      highest rate was observed in hyperinsulinemic hyperandrogenic subjects. Menstrual
      cyclicity was recovered in all patients under treatment. CONCLUSIONS: Our data
      show that metformin modulates ovarian function and greatly affects LH secretion
      through reduction of the hyperandrogenic condition. The highest rate of endocrine
      changes was observed in the hyperinsulinemic hyperandrogenic non-obese PCOS
      patients. Our study demonstrates that metformin administration is more
      appropriate in hyperinsulinemic hyperandrogenic non-obese PCOS patients.

PMID- 17454169
TI  - Prevalence of the metabolic syndrome in Asian women with polycystic ovary
      syndrome: using the International Diabetes Federation criteria.
AB  - BACKGROUND: Since insulin resistance and compensatory hyperinsulinemia are the
      major causes of the metabolic syndrome (MS) and are also the main pathophysiology
      of polycystic ovary syndrome (PCOS), PCOS women are at risk of MS. The aim of the
      present cross-sectional study was to determine the prevalence of MS in Asian
      women with PCOS using the International Diabetes Federation (IDF) criteria and to
      define the risk factors. METHODS: One hundred and seventy women with PCOS were
      enrolled in the study from September 3, 2002 to June 14, 2005. A 75-g oral
      glucose tolerance test with plasma glucose and serum insulin levels was
      performed. Also, blood samples were examined for fasting triglycerides, high
      density lipoprotein cholesterol and adiponectin levels. RESULTS: The mean (+/
      standard deviation) age, body mass index (BMI) and waist-to-hip ratio were 28.8+/
      5.9 years, 27.1 +/- 7.0 kg/m(2) and 0.85+/-0.06, respectively. The prevalence of
      MS was 35.3%. Age, BMI, waist circumference and all metabolic parameters were
      higher in PCOS women with MS than in those without MS. MS prevalence increased
      with age, BMI and insulin resistance as determined by homeostasis model
      assessment (HOMA-IR), but not with adiponectin after BMI adjustment. CONCLUSIONS:
      According to the IDF criteria, one-third of the PCOS women had MS. This study
      also showed that age, BMI and HOMA-IR are important risk factors for MS.

PMID- 17454170
TI  - Circulating concentrations of adiponectin and tumor necrosis factor-alpha in
      gestational diabetes mellitus.
AB  - Adiponectin and tumor necrosis factor-alpha (TNF-alpha) have been implicated in
      insulin resistance and diabetes mellitus (DM). In the present study we
      investigated levels of adiponectin and TNF-alpha and their relationships with
      each other and metabolic factors in women with gestational DM (GDM). Thirty-four
      pregnant women with GDM and 31 pregnant women with normal glucose tolerance (NGT)
      were included in the study. Plasma adiponectin levels were lower in GDM than in
      NGT (36.9 +/- 6.7 vs. 61.3 +/- 13.0 ng/ml, p = 0.028). Serum TNF-alpha levels
      were increased in GDM compared with NGT (20.5 +/- 2.4 vs. 14.0 +/- 1.5 pg/ml, p =
      0.042). After adjustment for pre-pregnancy and current body mass index (BMI),
      adiponectin levels correlated negatively with insulin resistance by homeostasis
      model assessment-insulin resistance (HOMA-IR) and 0-h and 1-h glucose both at
      glucose challenge test and oral glucose tolerance test in GDM. Adiponectin levels
      were correlated only with very low-density lipoprotein cholesterol and
      triglyceride levels in NGT. TNF-alpha levels were correlated with glycated
      hemoglobin in GDM. There was a significant positive correlation between TNF-alpha
      levels and pre-pregnancy and current BMI in GDM as well as NGT. HOMA-IR for
      adiponectin and pre-pregnancy BMI for TNF-alpha remained as significant
      determinants in multiple regression analyses. In conclusion, these data suggest
      that reduced adiponectin and increased TNF-alpha may be involved in the
      pathogenesis of GDM.

PMID- 17454171
TI  - Menopause-specific quality of life satisfaction in community-dwelling menopausal
      women in China.
AB  - The present study aimed to evaluate the satisfaction with quality of life of
      menopausal women living in an urban community of Beijing, People's Republic of
      China, using the Chinese version of the menopause-specific quality of life
      questionnaire (MENQOL). Menopause-related complaints were assessed for 353 women
      aged 40-60 years during their menopausal transition (MT) or postmenopause (PM)
      using MENQOL. The Kruskal-Wallis non-parametric test and Pearson correlation were
      used for statistical analysis. The mean age of the subjects was 51.20 +/- 4.62
      years. The most frequent symptom was 'experiencing poor memory' (84.1%) and the
      least frequent was 'dissatisfaction with personal life' (26.9%). Mean scores of
      vasomotor and sexual symptoms in PM women were higher than in MT women (2.60 +/-
      1.74 and 3.39 +/- 2.35 vs. 1.96 +/- 1.46 and 2.10 +/- 1.48, respectively; p =
      0.0001). The prevalence of menopause-related symptoms varied between self
      assessed health status groups (chi(2) = 29.12, p = 0.0001). In conclusion, MENQOL
      is a good self-administered tool in the assessment of climacteric complaints,
      with convenient application. The most frequent climacteric symptom of Chinese
      women living in an urban community was 'experiencing poor memory'. PM women
      seemed to suffer from more symptoms, especially in vasomotor and sexual domains,
      than did MT women. Symptom reports might be associated with self-assessed health
      status.

PMID- 17454172
TI  - CAPN10 UCSNP-43, UCSNP-19 and UCSNP-63 polymorphisms and metabolic syndrome in
      polycystic ovary syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder with
      individual susceptibility determined by genetic and environmental risk factors.
      Recently, studies have evaluated the CAPN10 gene in PCOS patients, suggesting
      that different alleles may play a role in PCOS susceptibility. We performed a
      cross-sectional study with 88 southern Brazilian hirsute patients with PCOS or
      idiopathic hirsutism (IH) to assess the influence of CAPN10 genetic variants on
      clinical and biochemical features of metabolic syndrome. PCOS patients were
      defined by oligo/amenorrheic cycles (<9 cycles/year), increased levels of serum
      testosterone and/or free androgen index, and exclusion of other disorders
      associated with hyperandrogenism. IH was diagnosed in hirsute patients with
      regular ovulatory cycles (luteal-phase progesterone levels >3.8 ng/ml), normal
      androgen levels, and without any known underlying disease (n = 29). Metabolic
      syndrome was defined according to the 2001 criteria of the National Cholesterol
      Education Program, Adult Treatment Panel III. UCSNP-43 polymorphism of CAPN10 was
      related to metabolic syndrome (p = 0.047) in PCOS; UCSNP-19 and UCSNP-63 were not
      associated with phenotypic traits in PCOS. These results provide evidence that
      CAPN10 gene UCSNP-43 polymorphisms may influence the PCOS metabolic phenotype.
      This should be further confirmed in large population-based studies.

PMID- 17454173
TI  - Pseudotumor cerebri from sinus venous thrombosis, associated with polycystic
      ovary syndrome and hereditary hypercoagulability.
AB  - OBJECTIVE: The association of pseudotumor cerebri, visual impairment,
      hypothyroidism, polycystic ovary syndrome (PCOS), and a hypercoagulable state due
      to a factor V and a prothrombin mutation has not been reported previously. CASE
      REPORT: A 20-year-old obese woman developed menstrual cycle irregularities since
      age 14 years, initially bitemporal and latter diffuse headache since age 14
      years, and bilateral visual impairment, described as sparkling black points.
      Ophthalmologically there was a recurrent papilledema. Clinical neurologic
      investigations revealed sore neck muscles and hirsutism. Magnetic resonance
      imaging of the brain, orbita and cervical spine, and investigations of
      cerebrospinal fluid were non-informative. Visually evoked potentials revealed
      demyelination of the optic nerves. Gynecologic investigations revealed PCOS and
      endocrinologic investigations hypothyroidism and hyperandrogenism. Tests for
      thrombophilia disclosed a heterozygote state for the G1.697A factor V Leiden and
      the G20.210A prothrombin mutation. A possible relationship between pseudotumor
      cerebri and the ophthalmologic, gynecologic, endocrinologic and coagulation
      abnormalities is discussed. CONCLUSIONS: For the first time we describe the
      association of pseudotumor cerebri, optic nerve demyelination, PCOS, other
      endocrinologic abnormalities, and thrombophilia due to a factor V and prothrombin
      mutation. A causal relationship between these abnormalities remains elusive.

PMID- 17454174
TI  - The price of a gift: an approach to receiving gifts from patients in psychiatric
      practice.
AB  - When a patient or patient's family presents a psychiatrist with a gift, the
      clinician is challenged to maintain appropriate professional boundaries but have
      the flexibility to respond with warmth and appreciation. The psychiatrist must
      consider such factors as the intention of the gift, its value to the patient, and
      the anticipated effect of accepting or refusing it on the patient and the
      treatment. Psychiatric practitioners are ethically obligated to consider
      patients' best interests when deciding about how to handle the offer of a gift.
      Ethical deliberations about such situations occur on a case-by-case basis and
      require careful analysis of how to promote the patient's best interest while
      adhering to professional ethics. In this article, members of the McLean Hospital
      Ethics Committee present a pragmatic model for managing the presentation of a
      gift from a patient or a patient's family member. The pragmatic model, which
      focuses on the practical results of accepting or declining the gift, minimizes
      the risk of exploiting the patient by accepting a gift or hurting the patient by
      declining it. We present five clinical cases that raise ethical dilemmas
      concerning patient gift giving in psychiatry and discuss each case from the
      standpoint of the pragmatic model.

PMID- 17454175
TI  - Risk-adjusting outcomes of mental health and substance-related care: a review of
      the literature.
AB  - Risk adjustment is increasingly recognized as crucial to refining health care
      reimbursement and to comparing provider performance in terms of quality and
      outcomes of care. Risk adjustment for mental and substance use conditions has
      lagged behind other areas of medicine, but model development specific to these
      conditions has accelerated in recent years. After describing outcomes of mental
      health and substance-related care and associated risk factors, we review research
      studies on risk adjustment meeting the following criteria: (1) publication in a
      peer-reviewed journal between 1980 and 2002, (2) evaluation of one or more
      multivariate models used to risk-adjust comparisons of utilization, cost, or
      clinical outcomes of mental or substance use conditions across providers, and (3)
      quantitative assessment of the proportion of variance explained by patient
      characteristics in the model (e.g., R(2) or c-statistic). We identified 36
      articles that included 72 models addressing utilization, 74 models of
      expenditures, and 15 models of clinical outcomes. Models based on diagnostic and
      sociodemographic information available from administrative data sets explained an
      average 6.7% of variance, whereas models using more detailed sources of data
      explained a more robust 22.8%. Results are appraised in the context of the mental
      health care system's needs for risk adjustment; we assess what has been
      accomplished, where gaps remain, and directions for future development.

PMID- 17454176
TI  - Head banging on an inpatient psychiatric unit: a vicious circle.

PMID- 17454177
TI  - Addicted to hair pulling? How an alternate model of trichotillomania may improve
      treatment outcome.

PMID- 17454178
TI  - Medicalizing alcoholism one hundred years ago.

PMID- 17454180
TI  - Connection between the meaning of health and interaction with health
      professionals: caring for immigrant women.
AB  - The meaning of health perceived by adult immigrant women in Canada is discussed
      from the perspectives of immigration, culture, and lived experience to understand
      their encounters with health care professionals. Authors base their findings on
      the thematic analysis of focus group data. Immigrant women viewed health as the
      outcome of a web of interactions between conditions of mental, physical, social,
      emotional, environmental, and spiritual well-being, appealing to both biomedical
      and phenomenological ideologies. Our analyses of qualitative data revealed that
      the disagreements noted by immigrant women when interacting with health care
      professionals were due to the discrepancies between their cultural views of
      health and the dominant biomedical perspective.

PMID- 17454181
TI  - Self-assessments of health by Korean immigrant women.
AB  - The purpose of this study was twofold: to discover how Korean immigrant women
      perceived their health and to identify associations between social indicators and
      the health of Korean immigrant women. Participants in the study comprised a
      nonprobability sample of 137 Korean immigrant women living in the United States
      who submitted questionnaires about their health to the researcher by U.S. mail in
      2004. Approximately 49% of the participants perceived their health as fair or
      poor. After age, income, education, marital status, and occupational status were
      controlled, the significant predictors of self-assessed health were involvement
      in exercise and length of residency in the United States. In future studies, the
      relationships between perception of health related to acculturation and self
      rating health should be investigated.

PMID- 17454182
TI  - The health of female Iranian immigrants in Sweden: a qualitative six-year follow
      up study.
AB  - Immigration affects life and health in many different ways. The purpose of this
      study was to identify and analyze female Iranian immigrants' perception of
      various factors that influence their health over time. Data collection was based
      on semistructured interviews with 10 female Iranian immigrants. Baseline
      interviews were conducted in 1996, with follow-up interviews in 2002. The results
      suggest that during the first decade after migration, female immigrants may
      overcome some health-related factors such as experiences of traumatic events.
      Other health determinants such as unemployment or experiences of discrimination
      and racism, however, were observed even two decades after migration.

PMID- 17454183
TI  - Knowledge and beliefs about health promotion and preventive health care among
      somali women in the United States.
AB  - We explored conceptualizations of health promotion and experiences with
      preventive health services among African refugee women. We asked 34 resettled
      Somali refugee women about their beliefs and experiences regarding health
      promotion and common preventive health care services in the United States.
      Interviews were audiotaped, transcribed, and analyzed using a grounded theory
      approach. Key themes were the importance of good hygiene, an adequate source of
      food and water, access to a regular source of health care, spirituality,
      traditional practices, and functioning well at home. All participants were
      familiar with the process and rationale for immunizations and routine medical
      examinations; few understood cancer screening services.

PMID- 17454185
TI  - Chat room computer-mediated support on health issues for aboriginal women.
AB  - Within contemporary health care, increases in chronic disease have necessitated a
      disease management focus. Given that chronic disease is managed, more so than
      cured, there are increased demands for greater participation by health care
      consumers and they are expectated to take on increased responsibility for self
      care. The emphasis on consumer responsibility has increased the significance of
      health-promoting behavior change in contending with contemporary health care
      concerns. In Canada, the reported inequity in health status between Aboriginal
      and non-Aboriginal Canadians further emphasizes the need for innovative health
      strategies. For Aboriginal women isolated by geography, changing societal norms
      (e.g., women working outside of the home, single parent families), and cultural
      distinction, online chat participation serves as a novel medium for the provision
      of health knowledge, support, and motivation within a virtual "neighborhood."
      Recognizing the significance of social support in the promotion of positive
      health behavior change, we investigated the theme of social support within health
      conversations among Aboriginal women participating in an online chat room.
      Content analysis was the primary methodological focus within a mixed methods
      approach. Of 101 health-based online conversations, the majority reflected one of
      three forms of social support: (1) emotional support, (2) informational support,
      or (3) instrumental support. The value of social support and social cohesion
      within health has been well documented. The current investigation suggests that
      "community" need not be physically constructed; virtual communities offer great
      potential for social cohesion around the issues of health and health care.

PMID- 17454184
TI  - ESL-speaking immigrant women's disillusions: voices of health care in Canada: an
      ethnodrama.
AB  - This article describes a research project that investigated whether language
      barriers play a part in immigrant women's health decreasing when they move to
      Canada. The findings are then represented in the form of an ethnodrama entitled
      "ESL-Speaking Immigrant Women's Disillusions: Voices of Health Care in Canada." I
      suggest that the play is catalytic because it encourages target audiences to
      empathize with the silenced voices of ESL-speaking immigrant women who live in
      Canada. I then conclude with a reflection about the potential that the genre of
      ethnodrama has for social change through its reflexive and critical nature.

PMID- 17454186
TI  - Borders of fertility: unplanned pregnancy and unsafe abortion in Burmese women
      migrating to Thailand.
AB  - Burmese women are forced to migrate to find work and security in Thailand due to
      the social, political, and economic disarray present in Burma. Unplanned
      pregnancies are common in this area, and one third of pregnancy loss is self
      induced. Poverty, lack of employment rights, and domestic violence are important
      factors in deciding to terminate the pregnancy. Women face multiple barriers in
      managing their fertility and use traditional techniques often with the help of
      lay midwives. The research methods include a retrospective review of medical
      records held in Thai and Burmese-led health facilities, as well as semistructured
      interviews and group discussions with Burmese women experiencing a pregnancy
      loss, Burmese traditional and modern health workers, and their husbands and
      community members.

PMID- 17454188
TI  - Hyposplenism: a comprehensive review. Part II: clinical manifestations,
      diagnosis, and management.
AB  - In the first part of this review, we described the physiological basis of splenic
      function and hypofunction. We also described the wide spectrum of diseases that
      can result in functional hyposplenism. In the second part of this review, we will
      be discussing the clinical picture, including complications, diagnostic methods,
      and management of hyposplenism.

PMID- 17454189
TI  - Impact of FLT3 internal tandem duplications on Indian acute promyelocytic
      leukemia patients: prognostic implications.
AB  - Despite recent advances in the treatment of acute promyelocytic leukemia (APL),
      early mortality and relapses still occur. With the view to evaluate the role of
      FLT3 mutation in APL, 54 patients (median age 28 years, range11-57 years, male to
      female ratio 1.2:1, median TLC 8.4 x 10(9)/l, range 1-170 x 10(9)/l) were studied
      by reverse transcriptase-PCR. Forty-two patients (77%) achieved first remission
      (CR1). Ten (18.5%) of the 54 patients had internal tandem duplication of exons 11
      and 12 of the FLT3 gene. The median TLC count was significantly higher in FLT3
      positive cases (Median TLC 55.0 x 10(9)/l) as compared to FLT3 negative cases
      (Median TLC 6.8 x 10(9)/l) (p = 0.001). Induction CR was much lower (40%) in
      FLT3/ITD positive cases as compared to 86% of FLT3/ITD negative cases (p =
      0.005). Early deaths too were significantly associated with FLT3/ITD positive
      cases (50 vs. 16% p = 0.033). The difference in the occurrence of bcr1 and bcr3
      isoforms was not statistically significant between the two groups. The data
      suggest that the presence of FLT3/ITD in APL patients confers a poor prognosis.

PMID- 17454190
TI  - Prognostic cytogenetic markers in childhood acute lymphoblastic leukemia: cases
      from Mansoura Egypt.
AB  - The objective of the work was to evaluate children with acute lymphoblastic
      leukemia (ALL) showing resistance to immediate induction chemotherapy in relation
      to conventional and advanced cytogenetic analysis. The study was conducted on 63
      ALL children (40 males and 23 females) with age range 4.5 months-16 years (mean =
      7.76 years). They included 37 cases who attained a true remission and 26
      complicated by failure of remission, early relapse or death. They were subjected
      to history, clinical examination and investigations including CBC, BM
      examination, karyotyping, FISH for translocations and flowcytometry for
      immunophenotyping and minimal residual disease diagnosis. Cases aged < 5 years;
      male sex with organomegaly had better remission although statistically
      insignificant. Initially low HB < 8 gm/dl, high WBCs and platelet counts
      >50.000/mm(3) also showed better but non-significant remission rates. Most of our
      cases were L(2) with better remission compared to other immunophenotypes. About
      40 informative karyotypes were subdivided into 15 hypodiploid, 10 pseudodiploid,
      8 normal diploid and 7 hyperdiploid cases; the best remission rates were noticed
      among the most frequent ploidy patterns. Chromosomes 9, 11 and 22 were the most
      frequently involved by structural aberrations followed by chromosomes 5, 12 and
      17. Resistance was noted with aberrations not encountered among remission group;
      deletions involving chromosomes 2p, 3q, 10p and 12q; translocations involving
      chromosome 5; trisomies of chromosomes 16 and 21; monosomies of 5 and X and
      inversions of 5 and 11. Our conclusions were that cytogenetic and molecular
      characterizations of childhood ALL could add prognostic criteria for proper
      therapy allocation.

PMID- 17454191
TI  - Collection of peripheral blood stem cells in new patients with myeloma receiving
      minimal or no prior cytoreductive therapy.
AB  - The aim of the study was to evaluate whether adequate stem cells (CD34+) could be
      harvested at presentation in myeloma patients such that high dose melphalan (HDM)
      with autologous stem cell rescue can be offered as primary therapy. The regimes
      either involved no prior cytoreductive chemotherapy (steroids only, n = 31) or a
      single course of VAD (n = 22). The median number of CD34 cells collected with
      steroids was 1.3 x 10(6) (0.2-5.6) compared to 4.6 x 10(6) (0.3-19.2) cells/kg
      with VAD (P < 0.0001). We conclude that it is possible to collect stem cells from
      myeloma patients at presentation with minimal prior therapy. Using this strategy,
      of a single prior course of chemotherapy followed by immediate harvest, it is
      feasible to offer early high-dose therapy in clinical situations where this is
      important.

PMID- 17454192
TI  - Clinical features and risk factors of pure red cell aplasia following major ABO
      incompatible allogeneic hematopoietic stem cell transplantation.
AB  - The objective of this paper was to study the incidence, risk factors, clinical
      outcome, management and prevention of pure red cell aplasia (PRCA) following
      major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo
      HSCT). We retrospectively analyzed 11 cases of PRCA from a series of 42 patients
      undergoing major ABO-incompatible allo-HSCT from April 1997 to December 2005.
      Eleven out of the 42 patients developed PRCA (26.1%). All the 11 cases of PRCA
      were in blood group O recipients of grafts from blood group A donor (n = 9) or
      blood group B donor (n = 2). The following factors were associated with an
      increased risk of PRCA: (1) blood group O recipient; (2) blood group A donor; and
      (3) blood group O/A in recipient/donor pair. Only blood group O/A in
      recipient/donor pair was identified as being significantly associated with the
      occurrence of PRCA by multivariate analysis. Six patients who received donor-type
      plasma exchange did not develop PRCA and among them 5 cases were the blood group
      O recipients. Eight patients obtained spontaneous remission and in the remaining
      3 patients 2 with long-lasting PRCA were successfully treated with plasma
      exchange with donor-type plasma replacement and the other one who was also
      complicated by EBV-associated lymphoproliferative disorder (EBV-PTLD) responded
      rapidly to anti-CD20 monoclonal antibody and achieved complete resolution of
      clinical finding and symptom of both EBV-PTLD and PRCA. We conclude that blood
      group A/O in donor/recipient pair is identified as being significantly associated
      with the occurrence of PRCA by multivariate analysis. Donor-type plasma exchange
      and anti-CD20 monoclonal antibody is an effective approach for the treatment of
      PRCA. PRCA could be prevented by plasma exchange prior to transplantation.

PMID- 17454193
TI  - Comparison of diagnostic criteria for polycythaemia vera.
AB  - Three sets of diagnostic criteria for polycythaemia vera (PV); the Polycythaemia
      Vera Study Group (PVSG) criteria (1975), the British Committee for Standards in
      Haematology (BCSH) criteria (1996) and the World Health Organisation (WHO)
      criteria (2001) have been described. We compared the ability of each set of
      criteria to accurately diagnose PV and differentiate it from secondary, apparent
      and idiopathic erythrocytosis. A cohort was drawn from a clinical database of
      erythrocytosis patients currently attending the Belfast City Hospital and the
      relevant information from the time of diagnosis for each patient was assessed
      according to each set of criteria, with the BCSH criteria used as a comparator.
      Sufficient data was available on 71 patients: 46 PV, 8 idiopathic, 8 apparent and
      9 secondary erythrocytosis. The BCSH criteria classified 34 of 46 patients
      (73.9%) as PV and the WHO criteria had a sensitivity and specificity of 100% for
      classifying PV. For idiopathic and apparent erythrocytosis, the specificity of
      the WHO criteria, compared to the BCSH criteria, declined to 66.7 and 87.5%,
      respectively. The PVSG criteria were limited by the unavailability of required
      data for some patients resulting in a sensitivity and specificity of 50% for PV
      and specificity of 100% for all other groups. The Janus kinase 2 (JAK2) V617F
      mutation was present in 34 (85.3%) PV, 2 (50%) IE, 1 (50%) apparent and no
      secondary erythrocytosis cases. We concluded that the BCSH criteria were the most
      accurate diagnostic criteria for PV as they had an acceptable level of
      sensitivity and could differentiate between PV and other erythrocytoses.

PMID- 17454194
TI  - Genetically heterogeneous origins of idiopathic erythrocytosis.
AB  - The idiopathic erythrocytosis (IE) group of disorders is defined by an absolute
      increase in red cell mass and hematocrit without elevation of the megakaryocytic
      or granulocytic lineages. It is associated with a wide range of serum
      erythropoietin (Epo) levels and broadly falls into groups of
      raised/inappropriately normal or low/undetectable Epo levels. A spectrum of
      molecular defects has been described in association with IE, which reflects the
      heterogeneity of this disorder. To date the most common identified cause of IE
      has been mutations in the von Hippel Landau (VHL) protein, which results in
      aberrant oxygen sensing and dysregulated Epo production. Studying the molecular
      basis of IE will provide insights into the control of Epo synthesis and Epo
      induced signaling pathways.

PMID- 17454195
TI  - Ovarian function after cancer treatment in young women affected by Hodgkin
      disease (HD).
AB  - We have evaluated the best method to assess the ovarian reserve and the ovarian
      protective effect of GnRH-analog (GnRH-a), in 29 women with Hodgkin's disease
      (HD) treated with chemotherapy (CHT). The ovarian reserve was studied by
      measuring the serum levels of follicle stimulating hormone (FSH), luteinizing
      hormone (LH), inhibin B, antimullerian hormone (AMH) and the ultrasound antral
      follicular count (AFC). The patients were randomly treated with or without GnRH
      a. At the time of study menstrual function was normal in 21 cases (72.4%), but
      absent in 8 (27.5%). Mean basal values of FSH, LH, AMH, inhibin B and AFC were
      normal in patients less than 30 years old and in the group treated four years or
      less before observation. AFC appeared to be the best marker of reduced ovarian
      reserve and a combination of AFC-AMH or inhibin B appeared the best predictor. In
      the GnRH-a group, no women had amenorrhoea, although ovarian reserve assessment
      was not significantly different from those who were not treated. The time
      interval from CHT was the only significant predictor of ovarian function in GnRH
      a treated patients. In conclusion, ovarian reserve evaluation, in young patients
      treated by CHT, can be performed by AFC. GnRH-a treatment does not have a
      protective effect, but could delay the development of ovarian failure.

PMID- 17454196
TI  - Gemcitabine, cisplatin and methylprednisolone (GEM-P) with or without Rituximab
      in relapsed and refractory patients with diffuse large B cell lymphoma (DLBCL).
AB  - This is the first report of the combination of gemcitabine, cisplatin and
      methylprednisolone (GEM-P) with Rituximab (GEM-PR) for diffuse large B-cell
      lymphoma (DLBCL). Thirty-nine patients with relapsed or refractory DLBCL in this
      study received GEM-P with (n = 24) or without Rituximab (n = 15) 64% patients had
      Stage III/IV disease. The overall response rate (ORR) was 59% (95% CI 42.1-74.4);
      11/39 (28%) patients attained complete response. Patients received a median of
      two cycles (1-4) of treatment. For GEM-PR group, the ORR was 67% (95% CI 45-84%)
      compared to 47% (95% CI 21-73%) in GEM-P alone. one-year progression-free
      survival was 51% (95% CI 28-69%) in GEM-PR group compared to 27% (95% CI 8-49%)
      in GEM-P alone (P = 0.04). GEM-P is an effective second-line regimen in patients
      with relapsed or refractory DLBCL and the addition of Rituximab appears to
      further improve outcomes.

PMID- 17454197
TI  - Rapid leukaemic evolution in a cutaneous blastic NK-cell lymphoma initially
      diagnosed as pseudolymphoma.

PMID- 17454198
TI  - Mixed-type autoimmune haemolytic anaemia: unusual cases and a case associated
      with splenic T-cell angioimmunoblastic non-Hodgkin's lymphoma.
AB  - The diagnosis of mixed-type autoimmune haemolytic anaemia (AIHA) is based on
      demonstrating the presence of "warm" IgG auto-antibody and "low titre" ( < 64 at
      4 degrees C), "high thermal amplitude" (reacting at or >30 degrees C) "cold" IgM
      auto-antibody. Mixed-type AIHA is uncommon. Red cell agglutination on the
      peripheral blood film is a common finding in mixed-type AIHA and can lead,
      initially, to a mis-diagnosis of cold haemmagglutinin disease (CHAD). Mixed-type
      AIHA is rare and can be idiopathic or secondary, often associated with systemic
      lupus erythematosus (SLE) and lymphoma. In general, patients with mixed-type AIHA
      show a dramatic response to steroid therapy and frequently require few or no
      transfusions. We report two unusual cases of mixed-type AIHA. Case one was
      unusual as the patient developed AIHA while on steroid medication. Case two, we
      believe, is the first reported case of splenic T cell angioimmunoblastic non
      Hodgkins lymphoma (NHL) associated with mixed-type AIHA. The patient failed to
      respond to steroids, intravenous immunoglobulin, chemotherapy and treatment with
      rituximab. The patient received 33 units of red cells over a 9-week period. She
      finally underwent splenectomy with resolution of haemolysis. DAT tested with
      monospecific reagents, and thorough serological investigations is required to
      reach the diagnosis of mixed-type AIHA. Awareness of this condition is important
      as management may be different from either treating warm AIHA or CHAD.

PMID- 17454199
TI  - Amyloidosis: a changing clinical perspective.
AB  - Primary amyloidosis is a plasma cell dyscrasia characterised by excess production
      of abnormal immunoglobulin light chains with their subsequent accumulation in
      kidneys, heart, liver as well as gastrointestinal tract and bone marrow 1-21, 2.
      These tissue deposits take the form of a fibrillar protein which damages the
      involved organ in proportion to the extent of the infiltration and roughly
      parallels the duration of the disease. Most cases have evidence of the underlying
      lymphoplasmacytoid neoplasm recognisable in two ways. Firstly, the monoclone
      appears in the serum [2]. Secondly is a morphologically and immunohistochemically
      distinctive cellular infiltrate in the bone marrow [3] that has a specific
      microscopic and ultrastructural pattern 4-54, 5. Interestingly occasional
      patients, who survive long enough, may progress to multiple myeloma [6] but the
      correlation is variable [7].

PMID- 17454200
TI  - Skull bone infarctive crisis and deep vein thrombosis in homozygous sickle cell
      disease- case report and review of the literature.
AB  - Here we describe an 8-year old male child with homozygous sickle cell disease who
      presented with left parietal skull bone infarction and, during his stay in
      hospital, developed a right femoral deep vein thrombosis (DVT), both uncommon
      complications of the disease. He initially presented with severe headache and
      generalised tenderness of the calvarium, which did not respond to simple
      analgesics. Scalp swelling in and around the left frontal (including left orbit)
      and parietal regions developed 24 h after presentation. The differential
      diagnosis included incipient stroke, acute sickle bone crisis and osteomyelitis,
      with a possible complication of epidural haematoma, or orbital compression
      syndrome. An initial exchange blood transfusion did not lead to appreciable
      reduction in opiate requirements. Significant symptomatic relief was attained
      only after a second exchange transfusion. The DVT developed at the site of
      catheterisation (right femoral vein), and this was treated with maximal doses of
      enoxaparin followed by warfarin. The child is now well and off anti-coagulants.
      In this article we present a review of the literature and discuss possible
      mechanisms of these complications in our patient.

PMID- 17454201
TI  - A comparison of conventional tube test and gel technique in evaluation of direct
      antiglobulin test.
AB  - In vivo coating of red cells by antibody and/or complement is detected using
      various sensitive techniques, however most hospitals even today rely on the
      conventional tube technique (CTT). We compared the performance of the CTT and
      recently introduced gel test (GT) in the evaluation of direct antiglobulin test
      (DAT). The CTT and GT were first compared using in-house prepared control cells.
      The polyspecific DATs were performed simultaneously by CTT and GT on 170
      consecutive blood samples. Positive samples were further tested for monospecific
      IgG and C3d by both techniques. GT demonstrated stronger agglutination scores (60
      vs. 43) compared to CTT using control cells. The sensitivity and specificity of
      the GT was 98.4 and 95.2%, respectively as compared to CTT for polyspecific DAT.
      Discordance between the two test systems was seen in 6/170 patients. Of these, 5
      were missed by CTT while GT failed to detect in vivo coating in only 1 case. The
      agreement between two methods of DAT was 96.4% (kappa = 0.926) using polyspecific
      AHG and 95.7% (kappa = 0.379) with monospecific anti-IgG. We conclude that GT is
      a better alternative to CTT for detecting red cell bound antibodies in various
      clinical conditions.

PMID- 17454202
TI  - Stem cells to gametes: how far should we go?
AB  - Murine embryonic stem cells have recently been shown to be capable of
      differentiating in vitro into oocytes or sperm. Should these findings be
      duplicated using human embryonic stem cells, this would raise a number of social
      and ethical concerns, some specific to these particular developments, others
      shared with other aspects of stem cell research. This review outlines the
      properties of stem cells and their conversion to gametes. Concerns raised include
      embryo destruction, quality of gametes derived in this way, possibility for
      children with two male biological parents, movement towards germ line gene
      therapy and 'designer babies', and the future impacts on health service
      provisions. It is important that public discussion of some of these issues should
      take place.

PMID- 17454203
TI  - Using evidence from randomized trials in fertility practice.
AB  - Randomized controlled trials (RCTs) are central to the understanding of treatment
      effectiveness and diagnostic test utility. If they are to be relied upon in
      clinical practice, data from trials should have three main attributes: validity
      (be free from bias); clinical relevance (be based on patients similar to your
      own, reporting outcomes that matter to them); and importance (demonstrate effect
      sizes that are large enough to justify the costs and risks entailed). With these
      principles in mind, this brief article reviews key questions to pose while
      deciding whether new evidence from RCTs should influence subfertility patient
      care.

PMID- 17454204
TI  - Confidence in the use of donor insemination: an evaluation of the impact of
      participating in a group preparation programme.
AB  - This paper argues that infertility can result in a range of negative emotional
      reactions, including a lack of confidence. This is more marked when donor
      insemination (DI) is used because of the additional shame this is associated
      with. Parents who do not feel confident may be less likely to share information
      about their use of DI with others and their child. Legislation in several
      countries has been introduced to abolish donor anonymity, but this has does not
      necessarily have an impact on parental confidence. In order to evaluate whether
      educational preparation programmes can impact on parental confidence and their
      intention to share information about DI, the confidence levels of 60 participants
      of three seminars were examined at three different points in time: before,
      immediately after and several months after attending the programme. Results
      indicate that most participants' confidence increased markedly as a result of
      attending an educational seminar. Furthermore, this increased confidence also
      impacted positively on the intention to share information about DI with future
      children. Both remained high several months after having attended the programme.
      These results point out that group preparation programmes can enhance levels of
      confidence, both as treatment is begun and as family building is undertaken.

PMID- 17454205
TI  - Infertility after fertility-preserving surgery for cervical carcinoma: the next
      challenge for reproductive medicine?
AB  - Radical trachelectomy is an operation developed as an alternative to radical
      hysterectomy for patients with small-volume, early stage cervical cancer, who
      wish to retain their fertility. The body of the uterus is left in place, so that
      future pregnancies can occur. Patients who have undergone radical trachelectomy
      may face problems conceiving naturally and may request assisted conception. This
      article explains the operation and the difficulties that those working in
      reproductive medicine may face.

PMID- 17454206
TI  - Initial management of infertility: an audit of pre-referral investigations and
      exploration of couples' views at the interface of primary and secondary care.
AB  - This study aimed to audit pre-referral investigations in primary care, and survey
      patients' views on the referral process from primary to secondary care. Referral
      letters and case notes of 250 consecutive couples referred to the Aberdeen
      Fertility Centre were audited in order to establish whether mid-luteal serum
      progesterone, rubella status and semen analysis had been performed. Couples
      attending a specialist hospital clinic for the first time completed a
      questionnaire on their experience of the referral process and consultation. Mid
      luteal progesterone was performed in 105 (51%) cases, rubella status checked in
      42 (20%) cases and semen analysis arranged in 70 (34%) cases. Overall, 274 (93%)
      patients were satisfied or very satisfied with the hospital consultation compared
      to 216 (84%) who utilised the general practitioner (GP) consultation (p < or =
      0.001); 79 (59%) women and 91 (68%) men wanted the current system of GP referral
      to continue (p < 0.001); and 74 (56%) women and 69 (52%) men (p < 0.001) favoured
      the option of direct self-referral. CONCLUSIONS: Despite high levels of
      satisfaction among couples, there is scope for further improvement in terms of
      pre-referral fertility investigations. Further evaluation of the referral process
      is needed, and potential changes to the existing system should be considered.

PMID- 17454207
TI  - Polycystic ovary syndrome and the single nucleotide polymorphisms of
      methylenetetrahydrofolate reductase: a pilot observational study.
AB  - Polycystic ovary syndrome (PCOS), insulin resistance and overall mortality due to
      diabetes and coronary artery disease are higher in South Asians than in
      Caucasians. AIMS: We compared the prevalence of the C677T and A1298C single
      nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene in South
      Asian and Caucasian women, its association with folate and homocysteine (Hcy)
      metabolism, and its relevance to future atherogenic events. METHODS AND RESULTS:
      71 women were recruited for the study: South Asian PCOS (21) plus controls (9)
      and Caucasian PCOS (25) plus controls (16). Anthropometric and laboratory
      parameters were compared. South Asian PCOS women were significantly
      hyperandrogenic and exhibited a greater degree of insulin resistance. Caucasian
      PCOS women had higher plasma Hcy concentrations with a 1.9 times higher frequency
      of the T allele than the South Asian PCOS group. In the presence of this variant
      allele, plasma Hcy levels appear to be higher in both PCOS groups. The South
      Asians had a 1.8 times higher frequency of the C allele than the Caucasians;
      however, the overall frequency was comparable in the two PCOS groups. The
      frequency of homozygosity, i.e. TT677 and CC1298, was 7.2% and 4.9% in the
      Caucasians and 0% and 16.6% in the South Asian recruits, respectively. Dietary
      inadequacies in the South Asian women can influence their plasma folate and B12
      concentrations resulting in hyperhomocysteinemia which, in combination with
      dyslipidaemia and insulin resistance, can lead to long-term atherogenic
      consequences. CONCLUSIONS: Current data suggests that the mechanisms of
      atherothrombosis have separate pathways in the two ethnic groups. Larger studies
      exploring the current theme need to be carried out in the PCOS groups to obtain
      adequate insight.

PMID- 17454208
TI  - Laparoscopy or laparotomy for distal tubal surgery? A meta-analysis.
AB  - Of couples with subfertility, 25% have complete or partial blockage of the
      fallopian tube. Since the advent of in vitro fertilization (IVF), the role of
      tubal surgery has diminished. However, this type of surgery continues to be
      undertaken on selected patients with mild tubal disease, and in those with severe
      tubal disease, in centres where IVF is not available. This systematic review was
      undertaken to compare pregnancy outcomes after laparoscopic surgery with that of
      open microsurgical technique. Studies comparing laparoscopic techniques with
      conventional microsurgery requiring laparotomy for treatment of distal tubal
      disease were included. The relevant trials were identified from Cochrane
      Menstrual Disorders and Subfertility Groups of Specialised Register of Controlled
      Trials (searched up to July 2005). The following strategies were adapted using
      the OVID platform, MEDLINE (1966 to July 2005), Cochrane Central Register of
      Control Trials, CENTRAL, and EMBASE (1980 to July 2005). Outcomes analysed were:
      'take home baby' rate, intrauterine pregnancy rate and ectopic pregnancy rate per
      pregnancy. Subgroup analysis was carried out to compare intrauterine pregnancy
      rate in the laparoscopy and conventional microsurgery groups according to the
      extent of tubal damage. Six relevant studies were identified. Overall, no
      significant difference was observed in the intrauterine pregnancy rate between
      the two groups, combined OR 1.32 (95% confidence interval [CI], 0.58 - 3.02). For
      patients with mild tubal disease, there was no significant difference in the
      intrauterine pregnancy rate between treatment and control group, OR 1.06 (95% CI,
      0.42 - 2.70). For patients with severe tubal disease, there was a significantly
      increased intrauterine pregnancy rate in the laparotomy group, OR 0.34 (95% CI,
      0.14 - 0.86). Appropriate patient selection is the main factor affecting outcome
      in terms of fertility. These data do not indicate a significant difference in
      pregnancy rates between open and laparoscopic techniques for lesser degrees of
      tubal damage. Other factors, such as costs and hospital stay, will come into the
      decision making, and are likely to favour laparoscopic techniques. If a decision
      is made to open the badly damaged tubes of a patient, then an open microsurgical
      technique should be employed.

PMID- 17454209
TI  - Is it ethically justifiable to cryopreserve oocytes and ovarian tissues of
      healthy women not facing premature ovarian failure, but seeking to extend their
      biological clocks?
AB  - Recent advances in oocyte and ovarian tissue cryopreservation technology have not
      only brought hope to women facing premature loss of ovarian function; it can also
      be utilized for healthy women seeking to extend their biological clocks. This is
      a major issue of contention in healthcare ethics. Proponents of this new
      technology argue that this enables women to fully pursue educational and career
      goals in their youth, whilst upon reaching middle age they would have more
      financial resources for their offspring. Nevertheless, this argument is flawed by
      the reality that even if the cryopreservation of oocytes and ovarian tissue were
      optimized, this would in no way be a guaranteed route for women to have
      biological children later in life. Moreover, because only a limited amount of
      autologous reproductive material can be cryopreserved and stored for a single
      healthy woman, there is a risk of material depletion before reproductive success
      is attained. Another prime consideration is the increased morbidity and mortality
      associated with clinical assisted reproduction in older women. Hence, it is
      suggested that the cryopreservation and storage of oocytes and ovarian tissues be
      restricted only to women facing the prospect of premature ovarian failure.

PMID- 17454213
TI  - Frederick P Zuspan and Marshall D Lindheimer.

PMID- 17454214
TI  - Maternal and umbilical sTNF-R1 in preeclamptic pregnancies with intrauterine
      normal and growth retarded fetus.
AB  - OBJECTIVE: The aim of this study was to determine the maternal and umbilical cord
      sTNF R1 serum levels in pregnancies complicated by severe preeclampsia with
      normal intrauterine fetal growth and in preeclamptic pregnancies with
      intrauterine growth retardation (IUGR). PATIENTS AND METHODS: The study was
      carried out on 8 patients with preeclampsia complicated by intrauterine growth
      retardation (group PI) and 18 preeclamptic patients with appropriate-for
      gestational-age weight infants (group P). The control group consisted of 18
      healthy normotensive delivering patients with singleton uncomplicated pregnancies
      (group C). Maternal and umbilical serum sTNF-R1 concentrations were estimated
      using a sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS AND
      CONCLUSIONS: Pregnant women with severe preeclampsia had higher maternal and
      umbilical serum sTNF-R1 levels than did normotensive controls. Furthermore
      significantly higher umbilical levels of sTNF-R1 were observed in the group of
      patients with preeclampisa complicated by IUGR, compared with preeclamptic
      patients with appropriate-for-gestational-age weight infants. The umbilical sTNF
      R1 levels in preeclamptic groups tended to be higher in comparison with the
      maternal levels. Our results and those of other reports seem to suggest that
      TNFalpha and sTNFR1 play a crucial role in pathogenesis and sequelae of
      preeclampsia with and without intrauterine growth retardation.

PMID- 17454215
TI  - Acute pancreatitis and cholecystitis associated with postpartum HELLP syndrome: a
      case and review.
AB  - We report a case of preeclampsia associated with hemolysis, elevated liver
      enzymes, and low platelet count (HELLP) syndrome and concomitant nonbiliary acute
      pancreatitis and cholecystitis in the first postpartum day. A thorough
      investigation ruled out known etiologies of both pancreatitis and cholecystitis.
      Following conservative treatment, the patient's HELLP syndrome, pancreatitis, and
      cholecystitis resolved on the third postpartum day. Preeclampsia is associated
      with microvascular abnormalities that may involve the splanchnic circulation.
      These abnormalities may cause not only HELLP syndrome but also pancreatitis and
      cholecystitis. Recognizing that ischemia can damage not only the liver but also
      the pancreas and gallbladder, could result in improvements in the diagnosis and
      management of pancreatitis in patients with preeclampsia.

PMID- 17454216
TI  - Rapid assessment of blood pressure in the obstetric day unit using Microlife MaM
      technology.
AB  - OBJECTIVE: To compare MaM technology with current methods of assessing blood
      pressure (BP) over time on the obstetric day unit. BACKGROUND: It is recommended
      that the average of repeated measures is used to confirm hypertension in
      pregnancy. The Microlife 3AC1 is a validated oscillometric device featuring "MaM"
      mode using the average of at least 3 BP readings 15 seconds apart. This allows
      rapid assessment of BP. The difference between each measurement is calculated and
      influences the percentage contribution to the final average reading. We compared
      MaM with readings taken in a conventional manner. METHODS: Blood pressure was
      measured in 30 hypertensive pregnant patients recruited from the obstetric day
      unit of a large teaching hospital. Single BP measurements were taken at 0, 15,
      30, 60, and 90 minutes using the Microlife BP 3BT0-A[2]. Simultaneous
      measurements (in the opposite arm) were also taken at 0 and 90 minutes using MaM
      technology. RESULTS: Systolic BP fell over 90 minutes (p = 0.035) compared with
      the first single reading, but diastolic BP did not (p = 0.54). The difference
      between the first MaM and the first single reading was significantly different
      for systolic BP (5.6 mm Hg, p = 0.017), but not for diastolic (0.6 mm Hg, p =
      0.39). The mean of all single readings and the first MaM reading were similar for
      both systolic and diastolic BP (SBP:0.3 mm Hg, p = 0.75, DBP: 0.2 mm Hg, p =
      0.87). CONCLUSIONS: White-coat hypertension exists for systolic BP in the
      obstetric day unit. The MaM technology allows rapid and accurate characterization
      of blood pressure equivalent to repeated measures over 90 minutes.

PMID- 17454217
TI  - Risk factors for cardiovascular disease in women with a history of pregnancy
      complicated by preeclampsia or intrauterine growth restriction.
AB  - OBJECTIVE: Women with a history of preeclampsia or intrauterine growth
      restriction (IUGR) have an increased risk for cardiovascular disease in later
      life. We determined the presence of traditional and novel risk factors for
      cardiovascular disease in these women. METHODS: We studied 256 women with a
      history of preeclampsia and 59 women with a history of intrauterine growth
      restriction. Fifty-three women with a history of uncomplicated pregnancy served
      as controls. We determined values for blood pressure, body mass index,
      concentrations of cholesterol, high-density lipoprotein cholesterol,
      triglycerides and lipoprotein (a), and insulin resistance. RESULTS: Women with a
      history of preeclampsia exhibited more risk factors for future cardiovascular
      disease such as dyslipidemia, hypertension, obesity, and increased insulin
      resistance compared with women with a history of uncomplicated pregnancy. Women
      with a history of IUGR have higher concentrations of cholesterol and show a
      tendency to higher BMI, higher triglyceride concentrations, and increased insulin
      resistance as compared with women with a history of normal pregnancy.
      CONCLUSIONS: Preeclampsia or IUGR may represent an early marker for increased
      risk for early cardiovascular disease.

PMID- 17454218
TI  - Angiotensin II receptor blockers in pregnancy: a case report and systematic
      review of the literature.
AB  - OBJECTIVE: To describe the case of a woman exposed to angiotensin-II receptor
      blockers (ARBs) in the preconceptional period and to systematically review the
      literature on the safety of these drugs when used by pregnant women. METHODS: The
      case was identified at the Korean Motherisk Program (Seoul). For the systematic
      review, we searched the PubMed for case reports, case series, and post-marketing
      surveys. RESULTS: A hypertensive woman was exposed to irbesartan prior to
      conception. The embryo had delayed development of upper and lower extremities and
      decreased digital groove. A karyotype identified a 45,XO Turner syndrome. The
      patient had a spontaneous abortion. Including the case reported here, 64
      published cases were identified in total; 57.8% had favorable and 42.2% had
      unfavorable outcomes. Duration of treatment during pregnancy among women who had
      adverse fetal outcomes was 26.3 +/- 10.5 weeks (mean +/- SD), compared with 17.3
      +/- 11.6 weeks in those who had favorable outcomes (p = 0.04). CONCLUSIONS:
      Exposure to ARBs for a period longer than the first trimester of pregnancy
      appears to be associated with a high risk for adverse fetal outcomes.

PMID- 17454219
TI  - Population-based analysis of hypertensive disorders in pregnancy.
AB  - OBJECTIVE: To determine the population-based incidence of hypertensive diseases
      in pregnancy in Western New York. METHODS: A database of 77,358 women with
      singleton pregnancies was analyzed using birth certificate data. The incidence of
      pregnancies complicated by gestational hypertension, preeclampsia, and eclampsia
      was determined. RESULTS: The overall incidence of pregnancy-associated
      hypertensive disease varied slightly from 1999 to 2003. The incidence of
      preeclampsia decreased from 1.8% to 1.1% (p < 0.01). This decrease persisted over
      time, despite controlling for known risk factors, such as body mass index, age,
      ethnicity, parity, smoking, diabetes, and chronic hypertension. CONCLUSION: The
      incidence of pregnancy-related hypertensive disorders slightly decreased in our
      population in the last 5 years, with a decline in the rate of preeclampsia
      accounting for this change. Further analysis may provide additional insights into
      the population-based incidence of preeclampsia.

PMID- 17454220
TI  - Predicting transformation from gestational hypertension to preeclampsia in
      clinical practice: a possible role for 24 hour ambulatory blood pressure
      monitoring.
AB  - OBJECTIVE: To identify parameters that may assist clinicians in predicting which
      women will develop preeclampsia (PE) after initially presenting with gestational
      hypertension (GH). METHODS: 118 women were recruited to the study with GH or PE.
      They were divided into three groups based on their diagnosis at delivery- (1) GH,
      (2) PE from the time of presentation, (3) those with an initial diagnosis of GH
      who progressed to PE. Women underwent 24 hour ambulatory blood pressure
      monitoring (ABPM) and had serum estrogen, progesterone, beta-HCG, leptin and
      adiponectin measured as possible predictors of transformation of GH to PE.
      RESULTS: Women who presented with GH, and progressed to PE, presented four weeks
      earlier (33 vs 37 weeks, p < 0.001) than those who did not progress. Women with
      PE, either as their initial diagnosis or after progression from GH, were
      delivered earlier (p < 0.001) and had more small for gestational age (SGA) babies
      than women with GH at delivery (p < 0.05). Those who developed PE after
      presenting with GH generally had higher blood pressures than those who remained
      as GH, significant for awake and 24 hour systolic blood pressures (p < 0.05).
      beta-HCG, estrogen, progesterone or leptin values were similar across the groups.
      Adiponectin was higher in women with established PE at presentation compared to
      women with GH (p = 0.02) but adiponectin failed to discriminate those women with
      an initial diagnosis of GH who progressed to PE. CONCLUSION: 24 hr ABPM may
      provide a non-invasive method of identifying this 'at risk' GH population,
      particularly in the case of early presentation.

PMID- 17454221
TI  - Protective action of a hydroalcoholic extract of a vinifera grape skin on
      experimental preeclampsia in rats.
AB  - OBJECTIVE: This study was designed to determine the protective effects of a
      vinifera grape skins extract (GSE, 200 mg/kg/day) on the deleterious effect
      observed in experimental preeclampsia, a condition where reduced nitric oxide
      production and increase in oxidative stress are present. METHODS: A condition
      similar to preeclampsia was induced by chronic inhibition of nitric oxide
      synthesis by L-NAME (60 mg/kg/day, orally) in pregnant rats. Blood pressure
      (systolic, mean and diastolic) was measured with the tail cuff method on day 20
      of pregnant control rats; pregnant rats treated with L-NAME, L-NAME plus GSE or
      GSE from day 13 to day 20 of pregnancy. Glucose was infused in anesthetized
      pregnant rats at day 20 and blood glucose and insulin were estimated at time
      zero, 15, 30, 45 and 60 minutes after beginning of glucose infusion. The number
      of fetus alive was also estimated at day 20 of pregnancy. In parallel, blood
      pressure was measured in non-pregnant and in non-pregnant rats treated with L
      NAME during 7 days. RESULTS: Increase in arterial pressure, reduction of alive
      fetus at the end of pregnancy and increase in insulin resistance was observed in
      pregnant L-NAME rats but not in pregnant L-NAME plus GSE rats or in pregnant GSE
      rats. Increase in arterial pressure was also observed in non-pregnant L-NAME
      rats. CONCLUSION: The present study demonstrated a protective effect of GSE in
      experimental preeclampsia since the deleterious effect induced by L-NAME that is,
      increased in stillbirth, hypertension and insulin resistance were significantly
      reduced by oral treatment with the extract. Probably an endothelium-dependent
      vasodilator effect and an antioxidant action play an important role on the
      effects of GSE in experimental preeclampsia.

PMID- 17454222
TI  - Maternal leptin concentrations are similar in African Americans and Caucasians in
      normal pregnancy, preeclampsia and small-for-gestational-age infants.
AB  - Leptin concentrations were measured in African American women in order to assess
      leptin's role in the increased frequency and severity of preeclampsia. In
      addition, leptin concentrations were measured in women who delivered small-for
      gestational-age (SGA) infants. A case-control study of African American and
      Caucasian women with normal pregnancies, preeclampsia, or SGA infants was done.
      Plasma leptin was quantitated by radio-immunoassay. The previously recognized
      pattern of increased leptin concentrations in preeclampsia was replicated. Leptin
      concentrations did not differ by race in any diagnostic category, and
      concentrations in women with SGA infants were not higher than those in healthy
      women. Differences in the frequency and severity of preeclampsia in African
      Americans cannot be explained by higher leptin concentrations.

PMID- 17454223
TI  - Reference intervals for anion gap and strong ion difference in pregnancy: a pilot
      study.
AB  - OBJECTIVE: Acid-base status and electrolyte levels change in normal pregnancy. We
      hypothesized that these physiological changes affect both anion gap and strong
      ion difference (SID). METHODS: A cross-sectional study of normal pregnant women
      (6 in the first trimester, 47 in the second trimester, 59 in the third trimester,
      and 13 postpartum). RESULTS: The anion gap in pregnancy (8.5 +/- 2.9 mEq/L) was
      less, compared to postpartum values (10.7 +/- 2.5 mEq/L), (p < 0.005). The SID,
      too, was lower (pregnancy, 38.3 +/- 2.9 mEq/L, postpartum 43.5 +/- 2.3 mEq/L, p <
      0.001), reflecting the combined influence of changes in albumin, SID, and PCO(2).
      CONCLUSION: Anion gap and SID both decrease in pregnancy, events which must be
      taken into account when managing acid-base disorders in gestation.

PMID- 17454224
TI  - L-arginine supplementation in patients with gestational hypertension: a pilot
      study.
AB  - OBJECTIVE: To evaluate the effects of L-arginine (L-Arg) supplementation on
      clinical outcomes and blood pressure (BP) changes in patients with gestational
      hypertension. METHODS: Patients with gestational hypertension and proteinuria (n
      = 28, >300 mg/24 h) and those without proteinuria (n = 46) were randomized in a
      double-blind design to receive either L-Arg (20g/500 mL intravenously daily, for
      5 days followed by 4 g/day orally for 2 weeks) or placebo (PL). The primary
      outcome variable was time from randomization to delivery (Latency). Automated BP
      readings were obtained every 2 hours, between 8.00 am and 8.00 pm daily, untill
      the sixth day after treatment. RESULTS: At inclusion, gestational age and
      proportions of patients with proteinuria did not differ significantly between the
      PL and L-Arg group. Latency was significantly longer in the L-Arg group compared
      with the PL group (19.5 +/- 16.9 vs. 31.7 +/- 25.2 days; p = 0.008). Compared
      with baseline, both systolic and diastolic BP 6 days after treatment were
      significantly reduced in the L-Arg group but not in the PL group. The subgroup of
      patients without proteinuria randomized to the group receiving L-Arg showed a
      trend to prolong pregnancy, to attenuate the evolution to PE, and to reduce the
      rate of low birth weight. CONCLUSIONS: The treatment with L-Arg seems promising
      in prolonging pregnancy and reducing blood pressure, particularly in patients
      with gestational hypertension and without proteinuria. This benefit should be
      confirmed in larger studies with the power to evaluate the effectiveness of L-Arg
      in preventing the development to preeclampsia.

PMID- 17454225
TI  - Prioritisation of tests for the prediction of preeclampsia complications: a
      Delphi survey.
AB  - BACKGROUND: Preeclampsia is associated with several maternal and fetal
      complications. Numerous tests - including patient history, physical examination
      findings, and laboratory investigations - are used to predict such complications
      in women with preeclampsia. At present, there are no robust systematic reviews or
      large studies examining the accuracy of tests that could predict complications in
      women with preeclampsia. OBJECTIVE: To identify the tests (which include items of
      history, examination, and investigations) that are clinically relevant in
      predicting maternal and fetal complications in women with preeclampsia. METHODS:
      A two-generational Delphi method was used to prioritize the clinically relevant
      tests that are considered helpful in predicting the maternal and fetal
      complications of preeclampsia. RESULTS: Blood pressure was rated as the best
      predictor of complications with mean score (+/- SD) of 4.7 (+/- 0.47), followed
      by proteinuria 4.6 (+/- 0.5) and liver function tests 4.5 (+/- 0.52). CONCLUSION:
      The list of tests that have been identified and prioritized will form the basis
      for future systematic reviews of the literature in this field.

PMID- 17454227
TI  - Unilateral hearing loss in infants: a call to arms!

PMID- 17454228
TI  - Audiological evaluation and self-assessed hearing problems in subjects with
      single-sided congenital external ear malformations and associated conductive
      hearing loss.
AB  - Previously, unilateral hearing impairment (UHI) has been considered of little
      consequence. However, a recent meta-analysis of children with UHI displayed
      educational and behavioural problems and possible delays of speech and language
      development. Further, patients with UHI consequently report hearing difficulties.
      Our study investigated hearing function, possible inner ear protection, and self
      assessed hearing problems in 57 subjects aged between 3-80 years with single
      sided congenital ear malformations and conductive UHI. Pure-tone thresholds and
      speech recognition (quiet, noise) were measured, and all patients completed a
      self-assessment questionnaire. Pure-tone thresholds corresponding to
      sensorineural function did not significantly differ between the normal (air
      conduction) and affected ear (bone conduction). However, speech recognition in
      both quiet and in noise was normal on the non-affected side but significantly
      worse on the malformed side. A moderate to high degree of self-assessed hearing
      problems were reported. In conclusion, hearing function in the affected ear was
      found to be subnormal in terms of supra threshold signal processing. Furthermore,
      a high degree of hearing difficulty was reported. Therefore, active treatment,
      surgery, or hearing amplification, might be considered.

PMID- 17454229
TI  - Hearing loss in relation to educational attainment and cognitive abilities: a
      population study.
AB  - Severe hearing loss among children has often been found to be associated with
      educational disadvantage and lower-than-average performance on cognitive tests,
      but less is known about the much more widespread milder levels of hearing loss.
      In a cohort of 22 162 young Danish men appearing before the draft board, about
      75% had normal hearing at 20 dB, and about 20% had mild hearing loss not worse
      than 25 dB in both ears for all tones less than 3000 Hz, and not worse than an
      average of 45 dB in both ears for all tones above 2000 Hz. The remaining 5% had
      more severe hearing loss. The proportions who had continued school education
      after age 16 years among the three groups were 51%, 42% and 34% respectively and
      their mean IQs were 101, 98 and 94. The evidence suggests that even mild hearing
      loss is associated with distinct educational and cognitive disadvantage which
      itself may result from difficulties in following classroom teaching.

PMID- 17454230
TI  - Neonatal hearing screening in Albania: results from an ongoing universal
      screening program.
AB  - The paper describes the outcomes of an ongoing universal hearing screening
      program in Tirana, Albania. The main objectives of the project were the
      evaluation of the feasibility of a neonatal hearing screening program in Albania,
      and an evaluation of the prevalence of risk factors in the NICU environment. One
      thousand five hundred and sixty-one (1561) infants from both the WB and NICU were
      screened with transient evoked otoacoustic emissions (TEOAE). A detailed history
      of risk factors was collected in each case, thus it was possible to evaluate the
      main factors influencing the output of the screening program. It was concluded
      that the program had the capacity to identify infants with congenital hearing
      loss provided that an informative component is well-structured and delivered.
      Also, although the prevalence of risk factors appeared high, the reduction of
      'case leakage' would allow the precise estimation of the incidence of hearing
      loss in the Albanian population.

PMID- 17454231
TI  - Apolipoprotein E alleles and sensorineural hearing loss.
AB  - The purpose of this paper is to determine if a relationship exists between APOE
      alleles and nonsyndromic, sensorineural hearing loss (SNHL) in adults. APOE
      genotype was determined on DNA obtained from a sample of 89 subjects with
      nonsyndromic, adult onset SNHL. Median age was 64 years old, and 51 (57%) were
      males. Allele frequencies in the study population were compared to those in the
      general population. Subjects were divided into two groups, one by severity of
      hearing loss and another by severity of impairment of word recognition. Each
      group was stratified by severity, and allele frequencies were compared to the
      general population. The study found that the APOE allele epsilon 4 was less
      prevalent in the study population with SNHL than in the general population. No
      relationship was found between the epsilon 4 allele and severity of hearing loss
      or severity of impairment of word recognition. The study revealed that the APOE
      epsilon 4 allele was under-represented in the study sample as compared to the
      general population. Future studies associating the epsilon 4 allele with SNHL
      need to be population-based, longitudinal, or done in younger subjects.

PMID- 17454232
TI  - Contralateral suppression of distortion product otoacoustic emissions: effect of
      the primary frequency in Dpgrams.
AB  - The amplitude of the 2f1-f2 distortion product otoacoustic emission (DPOAE) can
      be suppressed by presenting contralateral acoustic stimulation. To test the
      hypothesis that DPOAE contralateral suppression is influenced by the primary
      frequency in DPgrams, DPgrams were recorded at resolutions of 1, 8, and 17
      pts/octave, in the absence and presence of contralateral broadband noise (BBN).
      Participants were 20 normal-hearing human adults. In DPgrams with higher
      frequency resolutions, DPOAE suppression at amplitude peaks in DPgrams (8
      pts/octave: Mean = - 0.92 dB, SD = 0.71 for BBN at 60 dB SPL; 17 pts/octave: Mean
      = - 0.25 to -1.44 dB, SD = 0.51 to 0.86 for BBN at 40 to 70 dB SPL, respectively)
      was larger than the suppression at the dips in DPgrams (8 pts/octave: Mean = -
      0.13 dB, SD = 1.00; 17 pts/octave: Mean = - 0.03 to -0.73 dB, SD = 0.55 to 0.91).
      A larger intersubject variability in DPOAE contralateral suppression was observed
      at the dips. The results suggest that measuring DPOAE contralateral suppression
      at the primary frequencies corresponding to the peaks in DPgrams with higher
      frequency resolutions may improve the assessment of the efferent system function.

PMID- 17454233
TI  - Auditory and verbal working memory deficits in a child with congenital aniridia
      due to a PAX6 mutation.
AB  - PAX6 encodes a transcriptional regulator that is essential for brain
      morphogenesis. Heterozygous PAX6 mutation is associated with aniridia and
      abnormalities of the interhemispheric pathway in humans. We present the case of a
      12 year old boy with a known mutation of the PAX6 gene. There were parental
      concerns regarding his hearing, but repeated pure-tone audiograms were normal. He
      had a battery of standard central auditory tests, which gave abnormal results in
      tests which required auditory interhemispheric transfer (dichotic digits and
      pattern tests). A speech and language assessment, which yielded age-appropriate
      scores for speech, receptive and expressive language, revealed impaired verbal
      working memory. These test results were interpreted as indicating impaired
      auditory sensory and higher order interhemispheric transfer, consistent with
      reported findings in adults with mutations in PAX6, and correlated with his
      parent-reported hearing difficulties. This is the first report of central
      auditory and verbal working memory deficits in a child with a PAX6 mutation.
      Further research is needed to assess how these deficits impact on academic
      performance particularly in childhood.

PMID- 17454235
TI  - The grammatical morpheme deficit in moderate hearing impairment.
AB  - BACKGROUND: Much remains unknown about grammatical morpheme (GM) acquisition by
      children with moderate hearing impairment (HI) acquiring spoken English. AIMS: To
      investigate how moderate HI impacts on the use of GMs in speech and to provide an
      explanation for the pattern of findings. METHODS & PROCEDURES: Elicited and
      spontaneous speech data were collected from children with moderate HI (n = 10;
      mean age = 7;4 years) and a control group of typically developing children (n =
      10; mean age = 3;2 years) with equivalent mean length of utterance (MLU). The
      data were analysed to determine the use of ten GMs of English. Comparisons were
      made between the groups for rates of correct GM production, for types and rates
      of GM errors, and for order of GM accuracy. OUTCOME & RESULTS: The findings
      revealed significant differences between the HI group and the control group for
      correct production of five GMs. The differences were not all in the same
      direction. The HI group produced possessive -s and plural -s significantly less
      frequently than the controls (this is not simply explained by the perceptual
      saliency of -s) and produced progressive -ing, articles and irregular past tense
      significantly more frequently than the controls. Moreover, the order of GM
      accuracy for the HI group did not correlate with that observed for the control
      group. Various factors were analysed in an attempt to explain order of GM
      accuracy for the HI group (i.e. perceptual saliency, syntactic category,
      semantics and frequency of GMs in input). Frequency of GMs in input was the most
      successful explanation for the overall pattern of GM accuracy. Interestingly, the
      order of GM accuracy for the HI group (acquiring spoken English as a first
      language) was characteristic of that reported for individuals learning English as
      a second language. An explanation for the findings is drawn from a factor that
      connects these different groups of language learners, i.e. limited access to
      spoken English input. CONCLUSIONS: It is argued that, because of hearing factors,
      the children with HI are below a threshold for intake of spoken language input (a
      threshold easily reached by the controls). Thus, the children with HI are more
      input-dependent at the point in development studied and as such are more
      sensitive to input frequency effects. The findings suggest that optimizing or
      indeed increasing auditory input of GMs may have a positive impact on GM
      development for children with moderate HI.

PMID- 17454234
TI  - Evaluation of the clinical decisions made for 2-year-olds referred for speech and
      language therapy: a follow-up study.
AB  - BACKGROUND: Clinicians in the UK rely mainly on informal observations and
      structured and semi-structured tasks rather than standardized testing in their
      assessments of pre-school children referred with speech and language
      difficulties. The informal nature of the clinical decision-making process at this
      age is unsurprising given the dearth of research on early clinical referrals.
      Evidence of outcome for young children referred with speech and language problems
      typically begins in the early school years. AIMS: To examine the clinical
      decision-making of an experienced individual therapist by evaluating the extent
      to which follow-up evidence supported initial prognosis. METHODS & PROCEDURES:
      Forty-three randomly selected pre-school children referred to speech and language
      therapy services were seen at an average age of 2;8, when a range of informal
      assessments were carried out. They were followed up 18 months later. Outcomes
      were compared with initial diagnosis and prognosis. OUTCOMES & RESULTS: Initial
      judgements showed high associations between the type of problem, the presence of
      complex difficulties, severity ratings and prognosis. In line with previous
      findings, prognosis was significantly associated with the type of problem and
      severity at outcome, although overall changes were more pronounced than had been
      predicted. A minority of children were rated substantially worse than predicted
      at follow-up. CONCLUSIONS: This study illustrates the potential of this kind of
      approach to inform the process of decision-making and reflective clinical
      practice with very young children. Limitations of the study and implications for
      future action research are discussed.

PMID- 17454236
TI  - Prevalence of communication disorders compared with other learning needs in
      14,500 primary and secondary school students.
AB  - BACKGROUND: Prevalence data are of interest to health professionals and educators
      to assist in the planning of service delivery, allow for the calculation of the
      level of impact of intervention, and allow for the consideration of the
      boundaries between typical development and impairment. AIMS: To determine the
      prevalence of children with communication disorders and other learning needs as
      identified by their teachers within all primary and secondary schools in an
      Australian school district over a 3-year period. METHODS & PROCEDURES: Children
      with learning needs were identified from 14,514 students in the first year (wave
      1) and the 14,533 students 2 years later (wave 2). Children were identified via a
      four-phased data-collection process designed to reduce selection and
      misclassification bias. Identification included teacher training, teacher
      referral, confirmation by documentation from relevant professionals including
      speech and language therapists, audiologists, psychologists and doctors, and
      verification by the school district learning needs advisors. OUTCOMES & RESULTS:
      Overall 5309 students were identified as having some area of learning need in the
      first year and 4845 students were identified 2 years later. In order of
      prevalence, the areas of learning need were: specific learning difficulty (17.93%
      in wave 1; 19.10% in wave 2), communication disorder (13.04%; 12.40%), English as
      a second or other language (9.16%; 5.80%), behavioural/emotional difficulty
      (8.16%; 6.10%), early achiever/advanced learner (7.30%; 5.50%), physical/medical
      disability (1.52%; 1.40%), intellectual disability (1.38%; 1.20%), hearing
      impairment (0.96%; 0.80%), and visual impairment (0.16%; 0.30%). The male:female
      ratio for all children was 1.57:1 (wave 1) and 1.66:1 (wave 2) and was the
      highest for the categories of behavioural/emotional difficulty, communication
      disorders. There were significant differences between learning need and socio
      economic status quantile for all areas except early achievers/advanced learners
      and physical/medical disability. There was a higher prevalence of
      behavioural/emotional difficulty, and intellectual disability, in the lower socio
      economic status quantiles and a higher prevalence of communication disorders in
      the mid-to-high socio-economic status quantiles. More children were identified as
      having an additional learning need in grades 1-3 (5-9 years of age). The children
      who were perceived as requiring the highest level of teacher support were those
      with an intellectual disability. CONCLUSIONS: This study provides comparative
      prevalence data for children with additional learning needs. There was a high
      prevalence of children typically seen in the caseloads of speech and language
      therapists, and teachers identified that many of these children required high
      levels of support within the classroom.

PMID- 17454237
TI  - Addressing the needs of speakers with longstanding dysarthria: computerized and
      traditional therapy compared.
AB  - BACKGROUND: In clinical practice, it is common for speech and language therapists
      to discontinue dysarthria treatment when a plateau in spontaneous recovery is
      reached. However, there is some evidence from single-case research studies that
      people with chronic dysarthria can improve their speech with intervention several
      years after the onset of the disorder. If this is so, it can be argued that
      speech treatment should still be an option available to them. Motor learning
      principles suggest that in order to be effective, treatment needs to involve
      frequent, consistent practice with feedback. AIMS: To compare the effects of both
      traditional treatment for clients with longstanding, stable dysarthria with
      computerized speech therapy, which allows independent practice with feedback.
      DEVELOPMENT OF THE COMPUTER PROGRAM: A new computer program was developed through
      a European Union-funded, quality of life and management of human resources
      programme. The program was designed for use with people with speech disorders and
      was based on motor learning principles. Speech recognition technology was
      exploited to provide feedback on practice attempts. METHODS & PROCEDURES: Seven
      clients with longstanding, stable dysarthria completed a within-participant
      ABAC/ACAB case series design to compare 6-week blocks of weekly traditional
      treatment with 6-week blocks of computer-based treatment over a 6-month period.
      OUTCOMES & RESULTS: The findings suggest that the participants improved their
      speech with treatment. The computerized therapy was as effective as traditional
      treatment. The participants spent more time (37%) with the computerized therapy
      than with traditional practice techniques. CONCLUSIONS: The participants with
      longstanding dysarthria in this study made improvements to their speech with
      treatment using both traditional and computer-based techniques. Computers could
      provide a method of delivering an effective dysarthria treatment service without
      placing high demands on therapy resources.

PMID- 17454238
TI  - Speech and language therapy intervention in schizophrenia: a case study.
AB  - BACKGROUND: There is a significant body of evidence documenting the speech and
      language abnormalities found in adult psychiatric disorders. These speech and
      language impairments can create additional social barriers for the individual and
      may hinder effective communication in psychiatric treatment and management.
      However, the role of speech and language therapy in this patient population has
      not been extensively studied. AIMS: Speech and language therapy is reported in a
      53-year-old adult male patient who presented with severe poverty of speech as
      part of his diagnosis of schizophrenia. The aims of speech and language therapy
      focused on increasing the patient's verbal communication using a combination of
      traditional and non-traditional speech and language therapy methods. METHODS &
      PROCEDURES: Two phases of speech and language therapy were implemented. The first
      phase focused on desensitizing the patient to verbal communication. The second
      phase developed the patient's language productivity and increased his awareness
      of his social communication skills. Five separate measures were taken as
      baselines which were repeated at the end of the intervention. OUTCOMES & RESULTS:
      Post-intervention scores showed that the intervention was partly successful. The
      patient's verbal communication increased and he developed more appropriate social
      communication skills. His negative attitude to communication remained unchanged
      even though his self-evaluative status improved. CONCLUSIONS: The intervention is
      discussed in terms of the pre- and post-intervention measures and the role of
      speech and language therapy in schizophrenia. The study suggests that speech and
      language therapy can contribute to the understanding and management of
      schizophrenia and other adult psychiatric disorders.

PMID- 17454239
TI  - Factors influencing indirect speech and language therapy interventions for adults
      with learning disabilities: the perceptions of carers and therapists.
AB  - BACKGROUND: The working context for speech and language therapists (SLTs)
      delivering interventions to adults who have a learning disability has changed
      following the reorganization of care provision from hospitals to the community.
      Consequently, SLTs often deliver their care within a social model of disability
      through indirect intervention in collaboration with carers. However, there has
      been little research into how this approach works in practice. AIMS: To gain
      insight into the working context by identifying the key factors that influence
      indirect SLT interventions as perceived by SLTs and by paid carers from a range
      of service providers. To explore the implications of the results for the delivery
      of indirect SLT interventions and provide direction for further research. METHODS
      & PROCEDURES: Semi-structured interviews were used to collect data from an
      opportunistic sample of five SLTs working in Community Learning Disability Teams
      (CLDTs) and 12 carers from residential and day care services who had had
      experience of working with SLTs. The data were analysed inductively using a
      grounded theory framework. OUTCOMES & RESULTS: Two broad themes emerged for SLTs:
      roles and expectations, and changing carer behaviour through training. The key
      themes for carers were roles and values, awareness of communication needs, and
      motivation and opportunity to implement interventions. Four broad factors are
      suggested as having the potential to influence indirect interventions: diversity
      in the working context; possible conflict between the guiding values of SLTs and
      carers, particularly residential carers; collaboration and support for
      implementation; and SLT doubts about the effectiveness of formal carer
      communication training. CONCLUSIONS: The results add to the evidence that the
      delivery of indirect speech and language therapy interventions to people with
      learning disabilities is a complex activity demanding specialist skills from
      SLTs. The findings suggest that these should include expertise in professional
      collaborative and relational skills, and training methods and strategies. Action
      research is needed to test the validity of the findings and document their impact
      on indirect interventions in day-to-day practice. More research is needed on the
      effectiveness of modelling or demonstration as a training technique with carers.

PMID- 17454240
TI  - Clinical reasoning skills of speech and language therapy students.
AB  - BACKGROUND: Difficulties experienced by novices in clinical reasoning have been
      well documented in many professions, especially medicine (Boshuizen and Schmidt
      1992, 2000; Elstein, Shulman and Sprafka 1978; Patel and Groen 1986; Rikers,
      Loyens and Schmidt 2004). These studies have shown that novice clinicians have
      difficulties with both knowledge and strategy in clinical reasoning tasks. Speech
      and language therapy students must also learn to reason clinically, yet to date
      there is little evidence of how they learn to do so. AIMS: In this paper, we
      report the clinical reasoning difficulties of a group of speech and language
      therapy students. We make a comparison of a subgroup of these with experienced
      speech and language therapists' reasoning and proposes some methods and materials
      to aid the development of clinical reasoning in speech and language therapy
      students. METHODS & PROCEDURES: Student diagnostic reasoning difficulties were
      analysed during the assessment of unseen cases on an electronic patient database,
      the Patient Assessment and Training System (PATSy http://www.patsy.ac.uk) (Lum et
      al. 2006). Pairs of students were videoed as they completed a one hour assessment
      of one of three 'virtual patients'. One pair of experienced speech and language
      therapists, who were not part of the project team, also completed an assessment
      of one of these cases under the same conditions. Screen capture was used to
      record all on screen activity within PATSy web pages (i.e. mouse pointer
      position, hyperlink and button presses, page scrolling, browser navigation
      interactions and data entered); Verbal comments made by participants were
      analysed via a seven-level coding scheme that aimed to describe the events that
      occur in the process of diagnostic reasoning. OUTCOMES & RESULTS: Students
      displayed a range of competence in making an accurate diagnosis. Diagnostically
      accurate students showed use of specific professional vocabulary, and a greater
      use of firm diagnostic statements. For the diagnostically inaccurate students,
      typical difficulties were a failure to interpret test results and video
      observations, difficulty in carrying out a sequence of tests consistent with a
      diagnostic reasoning path, and problems in recalling and using theoretical
      knowledge. CONCLUSIONS AND IMPLICATIONS: We discuss how identification of student
      diagnostic reasoning difficulties can inform the design of learning materials
      intended to address these problems.

PMID- 17454241
TI  - Evidence of construct similarity in Executive Functions and Fluid Reasoning
      abilities.
AB  - Executive Functions and Fluid Reasoning are both considered to be core aspects of
      intelligence and mediated by frontal lobe functioning. However, both constructs
      considerably overlap, and the distinction between the two constructs is unclear.
      For this study, three measures of Executive Functions and three measures of Fluid
      Reasoning were administered to a group of participants. Significant correlations
      were found establishing an empirical association between these two constructs.
      Factor analysis and confirmatory factor analysis also provide evidence for
      construct similarity. Future research in defining these constructs for
      measurement purposes and using tests of these constructs in clinical practice is
      discussed.

PMID- 17454242
TI  - Quantitative analysis of myelinated axons of corpus callosum in the human brain.
AB  - In this study, the myelinated axons of the rostrum, genu, truncus and splenium
      parts of the corpus callosum were counted in the human brain by using a camera
      lucida. The numerical densities of these axons were compared with each other by
      means of quantitative analytical statistical methods. The number of myelinated
      axons of genu and truncus of the corpus callosum were found to be highest in
      number and they were nearly the same with each other. However, number of the
      myelinated axons of splenium was found to be lower in number, when compared with
      the other parts of corpus callosum.

PMID- 17454243
TI  - Methylphenidate (Ritalin): behavioral studies in the rat.
AB  - Attention Deficit Hyperactivity Disorder (ADHD) is a neuropsychiatric syndrome
      with an onset in childhood characterized by an inability to remain focused or to
      concentrate for prolonged periods of time. Children suffering from this disease
      are many times described as either inattentive or as hyperactive-impulsive
      depending on what form of the disease they manifest. Methylphenidate is the
      preferred treatment for this behavioral disorder and is used for long term
      disease management. Much still remains unknown concerning this stimulant and its
      effects on behavior and future abuse potential are pertinent questions. Since
      animal models are used to study the mechanism of drug action and rats are used
      often in drug studies, the objective of this review is to summarize the research
      reports that mainly have used rats as the model to investigate the action of
      methylphenidate. Topics discussed in this review include: (1) What effect does a
      single dose of methylphenidate have on locomotion activity; (2) Does repeated
      administration of methylphenidate result in tolerance or sensitization; and (3)
      Does methylphenidate have rewarding properties as measured by the self
      administration and condition placed preference paradigms.

PMID- 17454244
TI  - Aging, context memory and binding: a comparison of "what, where and when" in
      young and older adults.
AB  - There is evidence that age-related memory decline does not effect all types of
      episodic information to an equal extent, but that especially contextual memory
      and the integration of multiple features in memory deteriorate. The current study
      investigates contextual memory in a group of healthy young (N = 40) and older (N
      = 40) adults without dementia. All participants performed a computerized memory
      task assessing target memory (objects only), contextual memory (positions only)
      and memory for the combinations of two features (object, space, temporal order),
      that is, binding of target-context or context-context features. The results
      showed age-related decline on all task conditions. Furthermore, the performance
      on conditions requiring the binding of target and context features was affected
      to a greater extent in older adults compared to younger adults. These findings
      support the notion that a decline in contextual memory and binding might underlie
      poorer episodic memory in older participants.

PMID- 17454245
TI  - Estrus phase differences in female rats in morphine antinociception elicited from
      the ventrolateral periaqueductal gray.
AB  - Male rodents display greater systemic morphine antinociception than females which
      show their most marked effects during late diestrus or proestrus. Morphine (1-2.5
      mug) antinociception on the tail-flick test elicited from the ventrolateral
      periaqueductal gray was examined across estrus phases in female relative to male
      rats. Morphine antinociception was greatest in magnitude and potency in males
      followed by females tested during the proestrus phases relative to estrus and met
      diestrus. These data confirm morphine's systemic effects, implicate the
      ventrolateral periaqueductal gray in estrus phase-mediated effects, and
      underscore the control of the phase of the estrus cycle in examining sex
      differences in opioid antinociception.

PMID- 17454246
TI  - Intersensory facilitation in rapid single-joint voluntary activation and
      cancellation of arm movements.
AB  - The ability to initiate and cancel actions is a basic requirement for motor
      control in humans. Rapid movements to stationary targets over single joints are
      characterized by triphasic bursts of electromyographic (EMG) activity. While
      analysis of reaction time in motor activation tasks, in relation to different
      modalities of sensory inputs, has studied, its diametrically opposite task of
      motor cancellation has not been adequately addressed. We studied 9 normal right
      handed subjects using biceps (agonist) and triceps (antagonist) EMG recordings.
      Each underwent 3 motor activation and 3 motor cancellation tasks to light, sound
      and dual stimuli (6 blocks). The former consisted of ballistic elbow flexion over
      45 degrees, while the latter involved dropping of the forearm from a 45-degree
      elbow flexion angle. For motor activation, onset latencies and duration of
      agonist (Lat1, Dur1) and antagonist (Lat2, Dur2) muscles were recorded. For motor
      cancellation, onset latencies and duration of agonist (Lat1 only) and antagonist
      (Lat2, Dur2) were noted. Motor cancellation showed significantly shorter Dur2 EMG
      bursts (p < .0005) for all 3 stimuli conditions. Lat1 and Lat2 demonstrated
      significant correlation (p < 0.0005 for all), with the exception of dual stimulus
      condition during motor cancellation (p = 0.089). While dual stimulus during motor
      cancellation resulted in significantly shorter Lat2 (p = .013) in comparison with
      light and sound stimuli, this was not evident for motor activation tasks. The
      findings suggest that while a common central program exists for executing motor
      activation and cancellation, generation of antagonist activity in the latter may
      involve distinct neural pathways specifically robust to the effects of
      intersensory facilitation. This is discussed in relation to reciprocal motor
      oscillatory activity manifestations at the level of single joint movements.

PMID- 17454247
TI  - Attention or memory? Effects of familiarity and novelty on the Nc component of
      event-related brain potentials in six-month-old infants.
AB  - This study tested predictions from attentional, expectancy, and memory accounts
      of the Nc and early NSW components of ERPs in six-month-old infants. Visual
      stimuli were presented at the extremes of the probability continuum (a repeating
      stimulus versus novel stimuli) and at intermediate levels of probability (.80/.20
      oddball task). Probability effects were found for Nc, early NSW, and visual
      fixation performance but there were no differences in the ERPs or behavior to
      familiar or novel stimuli. The results are discussed in terms of attentional and
      memory based interpretations of the Nc component.

PMID- 17454248
TI  - Relationship of working memory and EEG to academic performance: a study among
      high school students.
AB  - Some biological and behavioral elements which could explain differences between
      high and low academic attainment (HA/LA) students were identified. The qEEG of
      subjects under the 10-20 derivation system was recorded at rest and while
      completing a 3-back working memory (WM) task. While completing the task LA
      students showed more theta and total absolute potency at rest, and HA individuals
      showed more energy in delta and theta frequencies in frontal regions; LA students
      made a higher number of mistakes while executing the WM task with no differences
      in reaction time between groups. We conclude that a diminished WM capacity is
      present in LA students.

PMID- 17454249
TI  - Histological and ultrastructural evidence for protective effects on aluminium
      induced kidney damage by intraperitoneal administration of alpha-tocopherol.
AB  - The nephrotoxic actions of aluminium (Al) arise from its accumulation in the
      kidneys, with the resultant degeneration of the renal tubular cells. It has been
      suggested that Al generates reactive oxygen species that cause the oxidative
      deterioration of cellular lipids, proteins, and DNA. To test this hypothesis, we
      have here investigated the potential for a protective role of alpha-tocopherol
      (vitamin E) during short-term exposure of rats to Al. Al was administered
      intraperitoneally either alone or in combination with vitamin E at a different
      point of abdomen, and the alterations in the kidney tissue were analyzed
      histologically. The results reveal that significant light microscopical and
      ultrastructural damage is caused by Al, whereas with the immediate
      coadministration of vitamin E, there is a protective effect against this damage
      to the kidney tissue. In Al-alone group, the glomeruli and proximal tubuli and
      the Bowman capsules had swellings, adherence, hemorrhage, increase in mesangial
      matrix, and marked interstitial tissue fibrosis, indicating severe damage. In the
      Al and vitamin E immediate coinjected group, renal tubule cells were almost of a
      normal appearance. A slight stenosis was seen in the capsular area in the
      Malpighi corpuscules. The tubular organization and the cytoplasmic basophilia
      were also much the same as in the control group, with the lumen clearly visible
      in most of the cortical tubuli. The results highlight the need to reduce exposure
      to Al, with particular attention being paid to the known sources of Al. At the
      same time, the maintenance of a diet that is rich in vitamin E should be
      beneficial in the alleviation of Al toxicity.

PMID- 17454250
TI  - Biological interactions of functionalized single-wall carbon nanotubes in human
      epidermal keratinocytes.
AB  - Carbon nanotube-based nanovectors, especially functionalized nanotubes, have
      shown potential for therapeutic drug delivery. 6-Aminohexanoic acid-derivatized
      single-wall carbon nanotubes (AHA-SWNTs) are soluble in aqueous stock solutions
      over a wide range of physiologically relevant conditions; however, their
      interactions with cells and their biological compatibility has not been explored.
      Human epidermal keratinocytes (HEKs) were dosed with AHA-SWNTs ranging in
      concentration from 0.00000005 to 0.05 mg/ml. MTT (3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide) cell viability decreased significantly (p < .05)
      from 0.00005 to 0.05 mg/ml after 24 h. The proinflammatory mediators of
      inflammation cytokines interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)
      alpha, IL-10, and IL-1beta were also assessed. Cytokine analysis did not show a
      significant increase in IL-6 and IL-8 in the medium containing 0.000005 mg/ml of
      AHA-SWNTs from 1 to 48 h. IL-6 increased in cells treated with 0.05 mg/ml of AHA
      SWNTs from 1 to 48 h, whereas IL-8 showed a significant increase at 24 and 48 h.
      No significant difference (p < .05) was noted with TNF-alpha, IL-10, and IL-1beta
      expression at any time point. Transmission electron microscopy of HEKs treated
      with 0.05 mg/ml AHA-SWNTs for 24 h depicted AHA-SWNTs localized within
      intracytoplasmic vacuoles in HEKs. Treatment with the surfactant 1% Pluronic F127
      caused dispersion of the AHA-SWNT aggregates in the culture medium and less
      toxicity. These data showed that the lower concentration of 0.000005 mg/ml of AHA
      SWNTs maintains cell viability and induces a mild cytotoxicity, but 0.05 mg/ml of
      AHA-SWNTs demonstrated an irritation response by the increase in IL-8.

PMID- 17454251
TI  - Coordination deficits induced in young adult mice treated with methylmercury.
AB  - Male and female C57BL/6J mice starting at postnatal (P) day 34 were exposed
      orally to five divided doses totaling 1.0 or 5.0 mg/kg of methylmercury (MeHg;
      given as methylmercuric chloride) or sterile deionized water in moistened rodent
      chow. After a 5-day waiting period, control and MeHg-treated mice were subjected
      to a standard battery of behavior tests for balance and motor coordination.
      Latency to falling on the accelerating rota-rod was significantly decreased in
      5.0 mg/kg MeHg-exposed mice when compared to control mice. In the open field,
      horizontal exploration with respect to total distance traveled during the first 5
      min on the first test day was significantly reduced in 1.0 mg/kg MeHg-exposed
      mice when compared to control mice. Rearing activity was not affected by MeHg
      treatment. In the footprint analysis, angle of foot placement measured in 1.0
      mg/kg MeHg-treated mice was significantly greater compared to control mice. Base
      stance and stride length were unaffected by MeHg treatment. On the vertical pole
      test, 10 mice from each treatment group fell off the pole during the time the
      pole was shifted from a horizontal position to a vertical position, whereas none
      of the control mice fell. These results indicate that short-term, low to moderate
      doses of MeHg in young adult mice can be detrimental to motor coordination and
      balance.

PMID- 17454252
TI  - 26-Week dermal oncogenicity study evaluating pure trans-capsaicin in Tg.AC
      hemizygous mice (FBV/N).
AB  - The objective of this study was to assess the oncogenic potential of trans
      capsaicin when administered weekly via topical application to the dorsal skin of
      Tg.AC mice for 26 weeks. Male and female Tg.AC mice (25 mice/sex/group) received
      dose formulations containing trans-capsaicin dissolved in diethylene glycol
      monoethyl ether (DGME). The positive control was tetradecanoylphorbol-13-acetate
      (TPA) dissolved in DGME. Appropriate controls, including a topical lidocaine
      local anesthetic pretreatment (4%w/w), were maintained. All groups were dosed
      once weekly, except for the TPA group, which was dosed twice per week. Analysis
      of the macroscopic observations after the final sacrifice revealed no noteworthy
      treatment-related findings, with the exception of dermal masses that were
      randomly dispersed throughout all treatment groups for both males and females.
      The frequency of dermal masses in the capsaicin-treated groups (at a dose level
      of up to 102 mg/kg and an application rate of 25.6 mg/cm2/kg/week) was not
      elevated in comparison to either concurrent vehicle or untreated controls. In
      contrast, a notable increase in the frequency of dermal masses was observed in
      the TPA-treated mice compared to both the concurrent vehicle and untreated
      controls. Dermal application of capsaicin resulted in no increased incidence of
      preneoplastic or neoplastic skin lesions. In contrast, over half the male and
      female mice exposed to TPA had multiple skin papillomas; the majority of the TPA
      treated animals either died early or was humanely euthanized due to tumor load.
      Spontaneously occurring neoplasms were not appreciably increased in capsaicin
      treated animals. Capsaicin-related non-neoplastic microscopic findings were seen
      sporadically in both genders and included acanthosis,
      hyperkeratosis/parakeratosis (primarily females), epidermal crusts, subepidermal
      fibrosis, epidermal ulcerations/erosions, and chronic-active inflammation. There
      was no evidence of a dose response in either the incidence or severity of these
      findings. The lidocaine- (at a dose level of 162 mg/kg and at an application rate
      of 40.5 mg/cm2/kg/week) and DGME-treated (at a dose level of 4.0 g/kg and at an
      application rate of 1 g/cm2/kg/week) control groups also did not display any
      evidence of increase in dermal masses. Based on these results, trans-capsaicin,
      lidocaine, and DGME should be considered nononcogenic in the Tg.AC mouse dermal
      model.

PMID- 17454253
TI  - Assessment of metal nanoparticle agglomeration, uptake, and interaction using
      high-illuminating system.
AB  - In the present study, an ultrahigh-resolution system was applied as a simple and
      convenient technique to characterize the extent of metal nanoparticle
      agglomeration in solution and to visualize nanoparticle agglomeration, uptake,
      and surface interaction in three cell phenotypes under normal culture conditions.
      The experimental results demonstrated that silver (25, 80, 130 nm); aluminum (80
      nm); and manganese (40 nm) particles and agglomerates were effectively
      internalized by rat liver cells (BRL 3A), rat alveolar macrophages (MACs), and
      rat neuroendocrine cells (PC-12). Individual and agglomerated nanoparticles were
      observed within the cells and agglomerates were observed on the cell surface
      membranes. The particles were initially dispersed in aqueous or physiological
      balanced salt solutions and agglomeration was observed using the Ultra Resolution
      Imaging (URI) system. Different methods, such as sonication and addition of
      surfactant (0.1% sodium dodecyl sulfate [SDS]) reduced agglomeration. Due to
      effects of SDS itself on cell viability, the surfactant could not be directly
      applied during cell exposure. Therefore, following addition of 0.1% SDS, the
      particles were washed twice with ultrapure water, which reduced agglomeration
      even further. Reducing the agglomeration of the nanoparticles is important for
      studying their uptake and in applications that benefit from individual
      nanoparticles such as diagnostics. In summary, this study demonstrates a simple
      technique to characterize the extent of nanoparticle agglomeration in solution
      and visualize nanoparticle (40 nm and larger) uptake and interaction with cells.
      Additionally, an example application of nanoparticle labeling onto the surface
      and neurite extensions of murine neuroblastoma cells (N2A) is presented as a
      potential imaging tool.

PMID- 17454254
TI  - Gene expression analysis on the early development of pig embryos exposed to
      malathion.
AB  - Malathion is a widely used pesticide and there is evidence that it could alter
      mammal's germ and somatic cells, as well as cell lines. There are not enough
      studies showing how the nonacute malathion doses affect gene expression. This
      study analyzes gene expression alterations in pig morular embryos exposed in
      vitro, for 96 h, to several malathion concentrations after in vitro
      fertilization. cDNA libraries of isolated morular embryos were created and
      differential screenings performed to identify target genes. Seven clones were
      certainly identified. Genes related to mitochondrial metabolism as cytochrome c
      subunits I and III, nuclear genes such as major histocompatibility complex I (MHC
      I), and a hypothetical protein related with a splicing factor were the target of
      malathion's deregulation effect. The widespread use of malathion as a pesticide
      should be regarded with reproductive implications and more detailed analysis
      would yield more about molecular mechanisms of malathion injury on embryo cells.

PMID- 17454255
TI  - Effects of mRg2, a mixture of ginsenosides containing 60% Rg2, on the ultraviolet
      B-induced DNA repair synthesis and apoptosis in NIH3T3 cells.
AB  - Ginseng has been used worldwidely as a traditional medicine of Asian countries
      for treatment of various diseases including cancer. The purpose of this study was
      to determine the effect of ginseng saponin mRg2, a mixture of ginsenosides
      containing 60% Rg2, on the repair and apoptosis of ultraviolet B (UVB)-exposed
      NIH3T3 cells. When cells were exposed to UVB and then incubated with normal
      growth medium for 48 h, cell viability, as determined by trypan blue exclusion
      assay decreased to about 25%. However, when mRg2 was included in the
      postincubation medium, the UVB-induced loss of cell viability was significantly
      reduced as compared with that postincubated in normal growth medium. 4,6
      diamidino-2-phenylindole (DAPI) staining showed that postincubation of the UVB
      exposed cells in medium containing mRg2 significantly reduced the apoptotic
      nuclear fragmentation. Interestingly, when cells were preincubated with mRg2 for
      24 h and then exposed to various doses of UV, the amount of repair synthesis
      significantly increased as compared with those in cells exposed to UVB alone.
      Western blot analysis indicated that the mRg2 postincubation after UVB exposure
      potentiated the level of p53 and p21. The level of Triton nonextractable
      proliferating cell nuclear antigen (PCNA) also remained elevated by mRg2
      postincubation. All these results suggest that mRg2 protects cells against UVB
      induced genotoxicity by increasing DNA repair and decreasing apoptosis, in
      possible association with the modulation of protein levels involved in cell cycle
      arrest or progression.

PMID- 17454256
TI  - Effect of the carotenoid-producing alga, Dunaliella bardawil, on CCl4-induced
      toxicity in rats.
AB  - Dunaliella bardawil is a carotenoid-producing alga that is being considered for
      use in nutraceuticals. To evaluate potential protective effects of consumption of
      this alga, rats were treated with two different doses of D. bardawil (2.5 and 5.0
      g kg(-1) body weight [bw]) as a biomass suspension daily for 14 days. Animals
      were tested against Carbon tetrachloride (CCl4; 2 ml kg(-1))-induced liver
      toxicity as measured by various biochemical marker enzymes in liver and blood.
      All measurements were taken 6 h following the single dose of CCl4. The results of
      this study show that there was a slight, but statistically significant mean serum
      enzyme values, with D. bardawil treatment, compared to higher mean values in
      animals receiving CCl4 alone. Lipid peroxidation is measured by thiobarbituric
      acid-reactive substance (TBARS) activity was likewise slightly less elevated with
      algae treatment. The results also demonstrated protection against DNA strand
      breaks in hepatocytes, as measured by single cell gel electrophoresis. Liver
      histopathology was less severe with D. bardawil treatment, supporting the
      apparent protective action of 14-day treatment on hepatic oxidative injury.

PMID- 17454261
TI  - The "End of the beginning" of the immunobiology of iNKT cells in health and
      disease.

PMID- 17454262
TI  - Does the developmental status of Valpha14i NKT cells play a role in disease?
AB  - CD1d-restricted natural killer T (NKT) cells that express an invariant Valpha14 T
      cell receptor (TCR) represent a subset of T cells implicated in the regulation of
      several immune responses, including autoimmunity, infectious diseases, and
      cancer. Their immunoregulatory functions are defined by their ability to rapidly
      and abundantly produce cytokines when activated. Unlike conventional T cells,
      Valpha14i NKT cells appear unique in their tendency to simultaneously produce
      both Th1 and Th2 cytokines, and whereas they enhance immunity in some disease
      models, they are reported to suppress immunity in others. This makes their effect
      on immune responses unpredictable. We reported recently that several important
      changes in gene expression occur in the course of Valpha14i NKT cell development.
      Immature and mature Valpha14i NKT cells differ in their expression of cytokines
      and chemokines, their cytotoxicity, and their expression of diverse chemokine
      receptors important for their migration. These results suggest that functionally
      distinct and developmentally linked subsets of Valpha14i NKT cells exist.
      Although mature NKT cells make up the majority of the peripheral NKT cells, a
      steady and sizable number of immature NKT cells migrate from the thymus into the
      periphery each day. These immature NKT cells, contrary to their name, are
      functional but are likely to behave quite differently from their mature
      counterparts. To what extent the developmental status of Valpha14i NKT cells
      plays a role in the outcome of any given immune response remains to be
      determined. Here we review the current knowledge of Valpha14i NKT cell
      development and propose that different developmental intermediates might be
      responsible for the various effects that have been observed in the many models
      where Valpha14i NKT cells have been implicated.

PMID- 17454263
TI  - The in vivo response of invariant natural killer T cells to glycolipid antigens.
AB  - Invariant natural killer T (iNKT) cells are a subset of T lymphocytes that
      recognizes glycolipid antigens presented by the major histocompatibility complex
      class I-related protein CD1d. Although iNKT cells have received a lot of
      attention as targets for the development of immunotherapies, few studies have
      investigated the in vivo response of iNKT cells to glycolipid antigen activation.
      Accumulating evidence indicates that iNKT cells generate a dynamic response to in
      vivo activation by glycolipid antigens that is characterized by surface receptor
      downmodulation, expansion, cytokine production, cross talk with other cells,
      homeostatic contraction, and acquisition of an anergic phenotype. These studies
      provide new insight into the biology of iNKT cells and have important
      implications for designing safe and effective iNKT cell-based vaccines and
      therapies.

PMID- 17454264
TI  - Regulation of type 1 diabetes by NKT cells.
AB  - Type 1 diabetes is an autoimmune disease due to the destruction of insulin
      producing pancreatic beta cells. Natural Killer T (NKT) cells are a T-cell subset
      that links the innate and adaptive immune systems. NKT cells play a key
      regulatory role in type 1 diabetes. The absence of NKT cells correlates with
      exacerbation of type 1 diabetes, whereas an increased frequency and/or activation
      of NKT cells prevents beta-cell autoimmunity. Various mechanisms are involved in
      the protective effect of NKT cells. The goal is now to translate knowledge gained
      from mouse models into human therapeutics.

PMID- 17454265
TI  - Therapeutic potential of CD1d-restricted invariant natural killer T cell-based
      treatment for autoimmune diseases.
AB  - CD1d-restricted invariant natural killer T (iNKT) cells are a unique subset of T
      cells that recognize glycolipid antigens presented by the CD1d molecule. iNKT
      cells participate in various kinds of immunoregulation due to a potent ability to
      produce a variety of cytokines. Recent advances in studies of novel synthetic
      glycolipid ligands has led to new strategies to manipulate the pleiotropic
      functions of iNKT cells. The molecular mechanism of selective cytokine production
      by glycolipid ligands will be discussed. We will also focus on the possible
      therapeutic application of such ligands for the clinical treatment of various
      autoimmune diseases.

PMID- 17454266
TI  - Invariant NKT cells and tolerance.
AB  - Invariant natural killer T (iNKT) cells are innate cells that can bias an immune
      response toward inflammation or toward a negative regulatory response. iNKT cells
      can produce cytokines immediately on exposure to activating signals, but the role
      of iNKT cells in the differentiation of T regulatory (Treg) cells and peripheral
      tolerance was elucidated only within the past decade. The purpose of this review
      is to outline the current knowledge of how iNKT cells function in various
      tolerance paradigms. The roles of iNKT cell in anterior chamber-associated immune
      deviation (ACAID), oral tolerance, other tolerance systems, and autoimmune
      diseases is discussed.

PMID- 17454267
TI  - Natural killer T cells regulate the development of asthma.

PMID- 17454268
TI  - Isotopic and other studies on the molecular origins of substrate regulation of
      some pyruvate decarboxylases: a reconsideration.
AB  - Solvent isotope effect and beta-secondary isotope effect studies of the steady
      state reaction of the pyruvate decarboxylase of Saccharomyces cerevisiae (ScPDC),
      which gains its full activity in a process requiring some seconds, suggested a
      model that ascribed the isotope effects to a reversible carbonyl-addition
      reaction between the 'regulatory pyruvate' molecule and the sulfhydryl group of
      Cys 221, occurring at the beginning and end of each catalytic cycle. The slow
      ('hysteretic') regulatory activation was thought to consist only of binding the
      regulatory molecule properly. Since the proposal of this model, much important
      progress in understanding both the structural and dynamic chemistry of ScPDC has
      been made in several laboratories. The purpose of this article is to review this
      new information and to evaluate the above model and others in the light of
      currently available evidence.

PMID- 17454269
TI  - The proton inventory technique in a dual mechanistic system: the spontaneous
      hydrolysis of ethyl formate.
AB  - Ethyl formate undergoes spontaneous hydrolysis through two parallel mechanistic
      pathways: water catalysis and specific hydrogen-ion catalysis. The proton
      inventory of the water reaction at 37.0 ( degrees )C was determined from the
      overall conversion curves, in H(2)O/D(2)O mixtures of deuterium atom fraction n,
      resulting in k(1)(n)=(2.1+/-0.1)x10(-5) s(-1) (1-n+0.42 n) (1-n+0.83 n)(2), in
      agreement with the results of six other cases of carboxylic acid derivatives.
      This result contributes to the validation of the accuracy of the proton inventory
      technique.

PMID- 17454270
TI  - A simple non-invasive method to detect and monitor hypercapnia: the sodium
      [13C]bicarbonate breath test.
AB  - Arterial partial pressure of carbon dioxide (paCO(2)) is commonly evaluated by an
      invasive test, the arterial blood gas analysis (ABG). The sodium
      [(13)C]bicarbonate breath test (SBT) can potentially estimate arterial paCO(2).
      We studied 55 subjects with respiratory disorders and performed the ABG and the
      SBT to determine if the SBT can predict hypercapnia. The percentage of (13)CO(2)
      recovered in exhaled breath at 30 minutes (PDR(30)) alone was able to
      discriminate clinically significant hypercapnia (>53 mmHg) with a sensitivity of
      82 % and specificity of 93 % (p<0.001). To evaluate the clinical utility of the
      SBT as a non-invasive substitute to repeated ABG, we monitored the progress of
      seven chronic obstructive pulmonary disease (COPD) patients on therapy with both
      the ABG and the SBT. The PDR(30) values from the SBT were able to correctly
      predict improvement or worsening of paCO(2) with 100 % accuracy. In conclusion,
      the SBT is a simple test that can be used in clinical practice to detect
      clinically significant hypercapnia and monitor COPD patients before and after
      therapy.

PMID- 17454271
TI  - Residence times and age distributions of spring waters at the Semmering catchment
      area, Eastern Austria, as inferred from tritium, CFCs and stable isotopes.
AB  - The groundwater system in the mountainous area of Semmering, Austria, was studied
      by environmental tracers in several karst springs. The tracers used included
      stable isotopes ((18)O, (2)H), tritium ((3)H) and chlorofluorocarbons (CFCs). The
      tracers provided valuable information in regard to (1) the mean altitude of the
      spring catchment areas; (2) the residence time and age distribution of the spring
      waters; and (3) the interconnection of the springs to a sinkhole. The combination
      of the stable isotopic data and the topography/geology provided the estimates of
      the mean altitudes of the catchment areas. Based on the stable isotopic data the
      recharge temperature of the spring waters was estimated. The smoothing of
      precipitation's isotopic signal in spring discharge provided information on the
      minimum transit time of the spring waters. Due to short observation time, (3)H
      data alone cannot be used for describing the mean residence time of the karst
      waters. CFCs, though useful in recognizing the co-existence of young (post-1993)
      water with old (CFC-free) water, could not be used to resolve age distribution
      models. It is shown in this article, however, that the combined use of tritium
      and CFCs can provide a better assessment of models to account for different
      groundwater age distributions. In Appendix A, a simplified method for collecting
      groundwater samples for the analysis of CFCs is described. The method provides a
      real facilitation for fieldwork. Test data are given for this sampling method in
      regard to potential contamination by atmospheric CFCs.

PMID- 17454272
TI  - Independence of alpine meadow plants from soil organic matter for nitrogen
      supply: evidence from stable nitrogen isotopes.
AB  - Stable nitrogen isotope signatures of major sources of mineral nitrogen
      (mineralization of soil organic nitrogen, biological N(2) fixation by legumes,
      annual precipitation and plant litter decomposition) were measured to relatively
      define their individual contribution to grass assimilation at the Haibei Alpine
      Meadow Ecosystem, Qinghai, China. The results indicated that delta(15)N values (
      2.40 per thousand to 0.97 per thousand) of all grasses were much lower than those
      of soil organic matter (3.4+/-0.18 per thousand) and mineral nitrogen (ammonium
      and nitrate together, 7.8+/-0.57 per thousand). Based on the patterns of stable
      nitrogen isotopes, soil organic matter (3.4+/-0.18 per thousand), biological N(2)
      fixation (0 per thousand), and precipitation (-6.34+/-0.24 per thousand) only
      contributed to a small fraction of nitrogen requirements of grasses, but plant
      litter decomposition (-1.31+/-1.01 per thousand) accounted for 67 %.

PMID- 17454273
TI  - Sulphur isotope compositions of components of coal and S-isotope fractionation
      during its combustion and flue gas desulphurization.
AB  - Sulphur isotope compositions were determined in two different Polish coals (hard
      coal and lignite) and by-products originating from their combustion. The
      desulphurization process was also investigated. It was demonstrated that
      desulphurization changes the isotopic composition of sulphur emitted in the form
      of SO(2) to the atmosphere even if the process is conducted in a different way
      (wet lime technology and electron beam method). This fact has to be considered in
      the studies regarding anthropogenic sulphur genesis and its fate in the
      environment.

PMID- 17454274
TI  - Determination of the soil-to-grass transfer of 137Cs and its relation to several
      soil properties at various locations in Serbia.
AB  - Transfer coefficients of (137)Cs from soil to grass were determined for the
      terrain around the city of Kragujevac in central Serbia. Mass activity
      concentrations of (137)Cs in soil and grass samples were determined with a high
      purity Ge-detector (HPGe). The activity concentration at the depth of 20 cm was
      found to be in the range of 14.92-124.05 Bq kg(-1), whereas the activity in grass
      for the same location was in the range of 4.60-84.95 Bq kg(-1). Transfer factors
      (TFs) were in the range of 0.07 up to 1.94. Dependences of TFs on different soil
      characteristics were presented graphically. Weak dependences were determined
      between them. Absalom's model was used to predict TFs based on soil
      characteristics: pH value, contents of clay, exchangeable potassium and humus. A
      comparison of measured and predicted values from Absalom's model is shown
      graphically. It has been found that Absalom's model might be carefully used for
      the prediction of (137)Cs in grass for specific regions.

PMID- 17454275
TI  - Comment on the paper 'Sulphur isotopic composition of H2S and SO4(-2) from
      mineral springs in the Polish Carpathians'.

PMID- 17454278
TI  - Community-based violence awareness.
AB  - Violence against women is a major influence on women's mental health. We used
      popular education techniques to train 14 Spanish-speaking women as promotoras
      (community health workers) to increase awareness about violence against women in
      low income Texas communities. These women then conducted over 80 presentations in
      Spanish in local community settings. The impact of the program on the promotoras
      and on women attending the presentations was evaluated using qualitative methods.
      This research lends support to the idea that nurses working in community mental
      health settings must use innovative primary prevention strategies and evaluation
      mechanisms to change awareness about violence against women.

PMID- 17454279
TI  - Comorbid medical illnesses and perceived general health among adult recipients of
      Medicaid Mental Health Services.
AB  - The purpose of this retrospective, cross-sectional, descriptive study was to
      measure self-reported frequencies of medical problems, overall health, and health
      related quality of life among mental health consumers. The sample included 787
      adults who had received a mental health service paid for by Medicaid over a one
      year period. The self-administered questionnaire included the 12-item Medical
      Outcomes Study (MOS) Short-Form (SF) Physical and Mental Health Summary Scales,
      and items about physical health problems and health-related quality of life. The
      majority of respondents (83.3%) reported that their general health was poor or
      fair. Frequently reported medical problems included arthritis, migraines, and
      high blood pressure. Knowledge of physical problems in persons with mental
      illness is essential for advanced practice nurses.

PMID- 17454280
TI  - Promoting coping: salutogenesis among people with mental health problems.
AB  - This article aims to illustrate how Antonovsky's salutogenic theory and its
      central concept of sense of coherence can be operationalized into salutogenic
      therapy principles and an intervention program for promoting a sense of
      coherence, coping, and mental health among people with mental health problems.
      The intervention is based on the following five basic components or therapy
      principles: (1) the health continuum model; (2) the story of the person; (3)
      health-promoting (salutary) factors; (4) the understanding of tension and strain
      as potentially health promoting, and (5) active adaptation. The program is a talk
      therapy group intervention and consists of 16 group meetings and homework. The
      intervention may serve as a guide to mental health nursing practice when coping
      is the main target.

PMID- 17454281
TI  - Assessment of acutely mentally ill patients' satisfaction of care: there is a
      difference among ethnic groups.
AB  - The relationship between quality of care and patient satisfaction has been
      documented. The specific research aim related to this study is to determine if
      differences exist among Caucasians, Asians, and Pacific Islanders who are
      hospitalized for an acute mental illness with regard to their perceived
      satisfaction with the care. The results of the overall study have been reported
      elsewhere. The sample was composed of 138 patients, of whom 34.7% were Caucasian,
      31.2% Pacific Islanders, and 34.8% Asians. Within 24 hours of discharge, patients
      completed the Perceptions of Care instrument. Caucasians were over-represented in
      our sample in comparison to their percentage in the general population of Hawaii.
      These patients were significantly more satisfied (p = .04) with their care than
      the other ethnic groups. No single variable was found to specifically indicate
      why they were more satisfied than Pacific Islanders and Asians.

PMID- 17454282
TI  - Can we achieve it?

PMID- 17454283
TI  - Why choose modafinil for excessive daytime sleepiness?

PMID- 17454284
TI  - In praise of unsung heroes.

PMID- 17454285
TI  - Reflections on a crazy mental health system.

PMID- 17454286
TI  - Mental health success stories: finding paths to recovery.
AB  - Recovery from serious and persistent mental illness (SPMI) is multi-faceted.
      Twenty individuals with SPMI who considered themselves successful in recovery
      participated in semi-structured interviews. Most were customers of mental health
      projects funded by NEBHANDS, a federal grant. Common themes on their paths to
      recovery included: (a) Finding acceptance and understanding of their mental
      illness; (b) Redefining their identity and preventing relapse; and (c) Finding
      ways to advocate to decrease stigma and help others along their paths. Also
      included in the interviews was the participants' descriptions of frequent
      barriers to recovery. An integration of informal networks with formal mental
      health services aided their recovery.

PMID- 17454287
TI  - Staff and patient perceptions of research in an integrated mental health service.
AB  - The purpose of this research was to survey staff and patients about their
      experience, knowledge, and attitudes regarding research. One hundred and sixty
      patients were interviewed using a questionnaire. In addition, a modified version
      of the same questionnaire was sent to multidisciplinary staff (n = 476), and
      about two-fifths (n = 181, 38%) were returned. Participants were interested in
      research and keen to know more about methods and processes. There were
      significant differences between staff and patients in terms of attitudes towards
      evidence-based practice and knowledge about research. The findings support the
      notion that staff and patients hold similar views about research methods and
      influences.

PMID- 17454288
TI  - Interpersonal rejection sensitivity: toward exploration of a construct.
AB  - This paper addresses the construct of interpersonal rejection sensitivity (IRS)
      as a phenomenon experienced by individuals in varying intensities. Selected
      theoretical frameworks are highlighted, as are developmental perspectives and
      research findings on the topic. Explication of this construct and better
      understanding by nurses of the pain felt by clients who experience rebuff could
      lead to more effective and sensitive interventions in a diversity of sittings. It
      is hoped that thoughtful exploration of this construct will lead to testable
      applications for practice.

PMID- 17454290
TI  - Creativity in older adults: a plethora of possibilities.
AB  - Aging continues to be an important topic of study. For many older adults, the
      elder years can be a challenging, if not difficult, time. Creativity
      interventions have been shown to positively affect mental and physiological
      health indicators. The process of creating and one's attitude toward life may be
      more important than the actual product or tangible outcome. While many activities
      are those typically thought of as creative, such as painting, there are also a
      number of useful interventions that are not traditionally identified as creative
      ones, but that are, in fact, creative activities. This paper describes recent
      work with creativity in older adults, including research and clinical projects,
      and earlier works that could be refined as creative interventions.
      Recommendations for further investigation of creativity also are presented.

PMID- 17454289
TI  - Parental stress among African American parents and grandparents.
AB  - The purpose of this study was to examine the relationships among parental stress,
      health (defined as level of systolic and diastolic blood pressure and body mass
      index), childcare characteristics, and social support. The study used a
      correlational research design and the setting was the metropolitan Detroit area.
      The sample consisted of 120 hypertensive African American parents and
      grandparents who reported caring for 1 to 9 children living in the household.
      Several variables (average diastolic blood pressure, number of
      children/grandchildren in home, child/grandchild is physically/mentally disabled,
      ability to decrease stress) were statistically significant predictors of parental
      stress. These results indicate that the multiple demands of parenting may become
      a barrier to making life-style changes for parents and grandparents diagnosed
      with hypertension. Nursing implications of the findings are discussed.

PMID- 17454291
TI  - Exploring the expanded practice roles of community mental health nurses.
AB  - Significant changes to the delivery of mental health services have resulted in
      the expansion of the community mental health nursing role. This qualitative study
      was undertaken to explore the extent to which community mental health nurses are
      currently engaged in expanded forms of practice. Focus groups were undertaken
      with community mental health nurses (n = 27) from metropolitan and rural
      Victoria, Australia. Thematic analysis identified the following major themes:
      reported practice, consumers as beneficiaries of expanded practice, risk of harm
      and litigation, and barriers to expanded practice. The findings emphasize the
      need for significant changes in current legislation if expanded practice for
      nurses is to become a reality.

PMID- 17454292
TI  - Cultural competence: what effect on reducing health disparities?

PMID- 17454293
TI  - Fallout from the biological model: implications for psychiatric mental health
      nurses.

PMID- 17454294
TI  - Psychopharmacology update: why choose quetiapine for bipolar illness?

PMID- 17454295
TI  - Common themes and variations in the rhodanese superfamily.
AB  - The rhodanese homology domain is a ubiquitous fold found in several
      phylogenetically related proteins encoded by eubacterial, archeal, and eukaryotic
      genomes. Although rhodanese-like proteins share evolutionary relationships,
      analysis of their sequences highlights that they are so heterogeneous to form the
      rhodanese superfamily. The variability occurs at different levels including
      sequence, active site loop length, presence of a critical catalytic Cys residue,
      and domain arrangement. Even within the same genome, multiple genes encode
      rhodanese-like proteins presenting with variably arranged rhodanese domain(s): as
      single or tandem domain(s), or combined with other protein domain(s). Given the
      highly variable organization of the rhodanese domain(s) and the context where it
      is found, here we review the structural organization and function of the
      rhodanese-like proteins. The overview of the most recent findings about rhodanese
      allow us to depict a superfamily of versatile proteins relying on persulfide
      chemistry to accomplish cellular functions spanning from resistance to
      environmental threats, such as cyanide, and key cellular reactions related to
      sulfur metabolism and progression of cell cycle.

PMID- 17454296
TI  - A discourse on cancer cell chemotaxis: where to from here?
AB  - The study of cancer cell chemotaxis on two-dimensional surfaces in vitro has
      relevance to the diverse migratory behaviours exhibited in vivo that involve a
      directed path. These may include translocation along collagen fibres, invasion
      into the basement membrane and across stroma, intravasation and extravasation to
      arrive at a secondary destination designated for cancer cell colonization.
      Chemotaxis invariably denotes the ability of cells to sense gradients, polarize,
      adhere and deadhere to substrate, and translocate in the right direction. Amongst
      these, the sensing function is perhaps the unifying aspect of different migration
      styles, permitting the cells to resolve its orientation and path. This review
      examines the decision-making processes that take place during chemotaxis and
      illustrates that a universal mechanism is involved. In various cell types from
      Dictyostelium to neutrophils, there are some unifying principles that dictate
      sensing and how the putative leading edge and trailing end of cells are
      determined. Some of these principles have recently been applied in the study of
      cancer cell chemotaxis albeit different pathways are substituted. In amoeboid
      like cancer cells, local excitation of the EGFR/PLCgamma/cofilin pathway and
      parallel, global inhibition of cofilin by LIMK occur to promote the asymmetric
      distribution and amplification of these internal signals in response to an
      external EGF gradient.

PMID- 17454297
TI  - T-armless tRNAs and elongated elongation factor Tu.
AB  - Most tRNAs share a common secondary structure containing a T arm, a D arm, an
      anticodon arm and an acceptor stem. However, there are some exceptions. Most
      nematode mitochondrial tRNAs and some animal mitochondrial tRNAs lack the T arm,
      which is necessary for binding to canonical elongation factor Tu (EF-Tu). The
      mitochondria of the nematode Caenorhabditis elegans have a unique EF-Tu, named EF
      Tu1, whose structure has supplied clues as to how truncated tRNAs can work in
      translation. EF-Tu1 has a C-terminal extension of about 60 aa that is absent in
      canonical EF-Tu. Recent data from our laboratory strongly suggests that EF-Tu1
      recognizes the D-arm instead of the T arm by a mechanism involving this C
      terminal region. Further biochemical analysis of mitochondrial tRNAs and EF-Tu
      from the distantly related nematode Trichinella spp. and sequence information on
      nuclear and mitochondrial DNA in arthropods suggest that T-armless tRNAs may have
      arisen as a result of duplication of the EF-Tu gene. These studies provide
      valuable insights into the co-evolution of RNA and RNA-binding proteins.

PMID- 17454298
TI  - H+-PPases: yesterday, today and tomorrow.
AB  - Suggestions by Calvin about a role of inorganic pyrophosphate (PPi) in early
      photosynthesis and by Lipmann that PPi may have been the original energy-rich
      phosphate donor in biological energy conversion, were followed in the mid-1960s
      by experimental results with isolated chromatophore membranes from the purple
      photosynthetic bacterium Rhodospirillum rubrum. PPi was shown to be hydrolysed in
      an uncoupler stimulated reaction by a membrane-bound inorganic pyrophosphatase
      (PPase), to be formed at the expense of light energy in photophosphorylation and
      to be utilized as an energy donor for various energy-requiring reactions, as a
      first known alternative to ATP. This direct link between PPi and photosynthesis
      led to increasing attention concerning the role of PPi in both early and present
      biological energy transfer. In the 1970s, the PPase was shown to be a proton pump
      and to be present also in higher plants. In the 1990s, sequences of H(+)-PPase
      genes were obtained from plants, protists, bacteria and archaea and two classes
      of H(+)-PPases differing in K(+) sensitivity were established. Over 200 H(+)
      PPase sequences have now been determined. Recent biochemical and biophysical
      results have led to new progress and questions regarding the H(+)-PPase family,
      as well as the families of soluble PPases and the inorganic polyphosphatases,
      which hydrolyse inorganic linear high-molecular-weight polyphosphates (HMW
      polyP). Here we will focus attention on the H(+)-PPases, their evolution and
      putative active site motifs, response to monovalent cations, genetic regulation
      and some very recent results, based on new methods for obtaining large quantities
      of purified protein, about their tertiary and quaternary structures.

PMID- 17454299
TI  - The positively charged residues in the fragment 71 - 77 of complexin is required
      for its binding to SNARE complex.
AB  - Complexin is a cytoplasmic protein that plays an important role in the
      neurotransmitters release triggered by action potential. Previous studies
      suggested that complexin performs its functions through interaction with the
      SNARE complex. The crystal structure of complexin/SNARE complex revealed that
      complexin binds to SNARE core complex in an anti-parallel conformation with its
      residues 48 - 70. However, the functions of the flanking sequences are unclear.
      In this paper, we demonstrate that the fragment 71 - 77 of complexin is
      indispensable for its binding to the SNARE complex. Moreover, this interaction
      can be impaired by abolishing the positive charges in the fragment 71 - 77, which
      suggests that the positive charges in the fragment 71 - 77 are important for the
      interaction between complexin II and the SNARE complex.

PMID- 17454300
TI  - Regulation of type II collagen expression by cyclin-dependent kinase 6, cyclin
      D1, and p21 in articular chondrocytes.
AB  - This study examined whether cell cycle regulatory proteins, such as cyclin
      dependent kinases (CDKs), cyclins, and CDK inhibitors, regulate type II collagen
      expression and mediate interlukin-1 (IL-1beta)-induced suppression of type II
      collagen expression in articular chondrocytes. IL-1beta inhibited type II
      collagen expression, but activated CDK6. Ectopic expression of CDK2 did not alter
      type II collagen expression. However, overexpression of CDK6 inhibited type II
      collagen expression, whereas inhibition of CDK6 activity blocked IL-1beta-induced
      suppression of type II collagen expression. IL-1beta upregulated the expression
      of cyclin D1, which is known to activate CDK6. In turn, overexpression of cyclin
      D1 suppressed type II collagen expression. In contrast to cyclin D1, IL-1beta
      triggered down-regulation of the CDK inhibitor, p21. Overexpression of p21
      blocked IL-1beta- or CDK6-induced suppression of type II collagen expression. Our
      results collectively indicate that CDK6/cyclin D1/p21 complex regulates type II
      collagen expression in articular chondrocytes.

PMID- 17454301
TI  - Activity of beta3-beta4 loop of the PH domain is required for the membrane
      targeting of SWAP-70.
AB  - SWAP-70 translocates to the plasma membrane in a phosphoinositide 3-kinase (PI 3
      kinase)-dependent manner and contributes to membrane ruffling. It binds to
      phosphatidylinositol trisphosphate (PtdIns(3,4,5)P(3)) through its PH domain,
      which is essential for the membrane translocation after EGF stimulation. We
      examined the behavior of the SWAP-70s which have mutations in the beta3/beta4
      loop of the PH domain. The two mutants fused to green fluorescent protein (GFP)
      carrying the mutations failed to translocate to the plasma membrane. The sole PH
      domains carrying the same mutations behaved similarly. The PtdIns(3,4,5)P(3)
      binding activity of two mutants was comparable to that of the wild-type protein.
      These results suggest that translocation of SWAP-70 largely depends on the
      activity of the PH domain, and that not only PtdIns(3,4,5)P(3) binding activity,
      but also some additional activity of the PH domain is required for the
      translocation.

PMID- 17454302
TI  - Which stage of the process of apotransketolase interaction with thiamine
      diphosphate is affected by the regulatory activity of the donor substrate?
AB  - The interaction of thiamine diphosphate (ThDP) with transketolase (TK) involves
      at least two stages: [formula: see text] During the first stage, an inactive
      intermediate complex (TK...ThDP) is formed, which is then transformed into a
      catalytically active holoenzyme (TK* - ThDP). The second stage is related to
      conformational changes of the protein. In the preceding publication (Esakova, O.
      A., Meshalkina, L. E., Golbik, R., Hubner, G., and Kochetov, G. A. Eur. J.
      Biochem. 2004, 271, 4189 - 4194) we reported that the affinity of ThDP for TK
      considerably increases in the presence of the donor substrate, which may be a
      mechanism whereby the activity of the enzyme is regulated under the conditions of
      the coenzyme deficiency. Here, we demonstrate that the substrate affects the
      stage of the reverse conformational transition, characterized by the constant k(
      1): in the presence of the substrate, its value is decreased several fold,
      whereas K(d) and k(+1) remain unchanged.

PMID- 17454303
TI  - Is the soluble guanylate cyclase pathway the only one available for nitric oxide
      (NO) signaling?

PMID- 17454304
TI  - How I became a biochemist ... and what happened next.

PMID- 17454305
TI  - Bile salt hydrolase, the member of Ntn-hydrolase family: differential modes of
      structural and functional transitions during denaturation.
AB  - Conformational transitions and functional stability of the bile salt hydrolase
      (BSH; cholylglycine EC: 3.5.1.24) from Bifidobacterium longum (BlBSH) cloned and
      expressed in E. coli were studied under thermal, chemical and pH-mediated
      denaturation conditions using fluorescence and CD spectroscopy. Thermal and Gdn
      HCl-mediated denaturation of BlBSH is a multistep process of inactivation and
      unfolding. The inactivation and unfolding of the enzyme was found to be
      irreversible. Enzyme activity seems sensitive to even minor conformational
      changes at the active site. Thermal denaturation as such did not result in any
      insoluble protein aggregates. However, on treating with 0.25 - 1 M Gdn-HCl the
      enzyme showed increasing aggregation at temperatures of 40 - 55 degrees C
      indicating more complex structural changes taking place in the presence of
      chemical denaturants. The enzyme secondary structure was still intact at acidic
      pH (pH 1 - 3). The perturbation in the tertiary structure at the acidic pH was
      detected through freshly formed solvent exposed hydrophobic patches on the
      enzyme. These changes could be due to the formation of an acid-induced molten
      globule-like state.

PMID- 17454306
TI  - Cimifoetisides VI and VII Two new cyclolanostanol triterpene glycosides from the
      aerial parts of Cimicifuga foetida.
AB  - Two new cyclolanostanol triterpene glycosides, cimifoetiside VI (1) and
      cimifoetiside VII (2), and one known compound were isolated from the aerial parts
      of Cimicifuga foetida L. On the basis of spectral and chemical evidences, the
      structures of 1 and 2 were elucidated to be (23R,24S)-24-O-acetylisodahurinol-3-O
      beta-d-galactopyranoside and (23R,24R)-24-O-acetylshengmanol-3-O-beta-d
      glucopyranosyl-(1'' --> 2')-beta-d-xylopyranoside. The known compound was
      identified as (23R,24R)-24-O-acetylshengmanol-3-O-beta-d-galactopyranoside (3).

PMID- 17454307
TI  - A new semisynthetic ocotillol-type saponin and resuscitation of haemorrhagic
      shock.
AB  - A new ocotillol-type saponin (PGQ) has been semisynthesised from 20(S)
      ginsenoside Rg3 for the first time, in with a yield of 73%, by oxidation and
      cyclisation of the side-chain. Its structure was characterised by IR, HR-MS, (1)H
      NMR, (13)C NMR, (1)H-(1)H COSY, DEPT, HMBC and HMQC spectroscopy as 3-O-[beta-D
      glucopyranosyl-(1-2)-beta-D-glucopyranosyl]-dammar- 20S,24S-epoxy-3beta,12beta,25
      triol (1). The saponin produced a beneficial effect on resuscitation of
      haemorrhagic shock as follows: first, it could significantly rise increased mean
      arterial pressure; second, it could increased blood oxygen content; third, it
      could markedly decreased serum lipoperoxidase and increased superoxide dismutase
      (SOD) activities. Thus, the saponin had the effect of an anti-haemorrhagic shock.

PMID- 17454308
TI  - A novel macrocyclic spermine alkaloid from Incarvillea sinensis.
AB  - A novel macrocyclic spermine alkaloid incasine C' (1), along with a known
      compound incasine C (2), were isolated from the whole plants of Incarvillea
      sinensis, and their structures were elucidated on the basis of chemical and
      spectroscopic evidence.

PMID- 17454309
TI  - Two new triterpenoid saponins from Ardisia crenata.
AB  - Two new triterpenoid saponins, ardisicrenoside K (1) and ardisicrenoside L (2),
      have been isolated from the roots of Ardisia crenata Sims. Their structures have
      been determined as 3beta-O-[alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D
      glucopyranosyl-(1 --> 4)-[beta-D-glucopyranosyl-(1 --> 2)]-alpha-L
      arabinopyranosyl]-13beta,28-epoxy-16-oxo-30,30-dimethoxyoleanane and 3beta-O
      [beta-D-xylopyranosyl-(1 --> 2)-beta-D-glucopyranosyl-(1 --> 4)-[beta-D
      glucopyranosyl-(1 --> 2)]-alpha-L-arabinopyranosyl]-13beta,28-epoxy-16alpha,20
      dihydroxyoleanane by means of chemical evidences and spectral analysis. Their
      weak anti-fungal activity against the plant pathogenic fungus Pyricularia oryzae
      was evaluated in vitro.

PMID- 17454310
TI  - Studies on chemical constituents of Polygonum perforliatum L.
AB  - Two new apianen lactones, named as guanyeliaoine I (1) and guanyeliaoine II (2),
      have been isolated along with seven known compounds from Polygonum perforliatum
      L. (Chinese name "Guanyeliao", Berberidaceae). Their structures were deduced on
      the basis of spectral data and chemical methods.

PMID- 17454311
TI  - Effect of astragaloside on cardiomyocyte apoptosis in murine coxsackievirus B3
      myocarditis.
AB  - Astragaloside is the major component of Astragalus membranaceus, one of the
      Chinese medical herbs, and has several pharmacological actions on cardiovascular
      system, including positive inotropic, anti-arrhythmia and anti-oxidant
      activities. We have investigated the effect of astragaloside on cardiomyocyte
      apoptosis and expression of apoptosis-associated genes in mice with
      coxsackievirus B(3) (CVB(3))-induced myocarditis, the former of which has been
      detected by terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end
      labeling (TUNEL) assay and the latter determined by using a focused microarray.
      Results showed that cardiomyocyte apoptosis and expression of various apoptosis
      associated genes are inhibited after treatment with astragaloside. The anti
      apoptotic activity of astragaloside may contribute to the improvement of clinical
      outcomes in treating myocarditis with pharmaceutics of Astragalus membranaceus.

PMID- 17454312
TI  - Two new naphthoquinones from the stem of Diospyros maritima.
AB  - Two new naphthoquinones, 2-ethoxy-8'-hydroxyisodiospyrin (1) and 3-ethoxy-8'
      hydroxyisodiospyrin (2), together with two known naphthoquinones, 6-hydroxy-5
      methoxy-2-methyl-1,4-naphthoquinone and bisisodiospyrin were isolated from the
      stems of Diospyros maritima. The structures of 1 and 2 were established on the
      basis of spectroscopic data.

PMID- 17454313
TI  - The metabolites of a mangrove endophytic fungus, Penicillium thomi.
AB  - The chemical constituents research of the fermentation of Penicillium thomi
      separated from the root of Bruguiera gymnorrhiza led to the isolation of a new
      compound, 4',5-dihydroxy-2,3-dimethoxy-4-(hydroxypropyl)-biphenyl (1) and 11
      known compounds. The structures of isolated compounds were determined by
      spectroscopic and chemical analysis. Their cytotoxic effects against three human
      cancer cell lines (A549, HepG2 and HT29) were also investigated.

PMID- 17454314
TI  - 9, 10-Dihydrophenanthrene derivatives from Pholidota yunnanensis and scavenging
      activity on DPPH free radical.
AB  - Three new 9,10-dihydrophenanthrene derivatives named phoyunnanins A-C, together
      with six known 9,10-dihydrophenanthrene constituents, 4,4',7,7'-tetrahydroxy-2,2'
      dimethoxy-9,9',10,10'-tetrahydro-1,1'-biphenanthrene (4), lusianthridin (5),
      eulophiol (6), 2,4,7-trihydroxy-9,10-dihydrophenanthrene (7) and imbricatin (8),
      were isolated from the 60% ethanolic extract of air-dried whole plant of
      Pholidota yunnanensis Rolfe. The structures of phoyunnanins A-C were established
      as 6-[2'-(3',3''-dihydroxy-5'-methoxybibenzy)]-4,7-dihydroxy-2-methoxy-9,10
      dihydrophenanthrene (1), 6-[6'-(trans-3',3''-dihydroxy-5'-methoxystilbeny)]-4,7
      dihydroxy-2-methoxy-9,10-dihydrophenanthrene (2) and 4,4',7,7'-tetrahydroxy-2,2'
      dimethoxy-9,9',10,10'-tetrahydro-1,6'-biphenanthrene (3), respectively, on the
      basis of the spectroscopic analysis. All eight compounds (1-8) were found to show
      the DPPH free radical scavenging activity with EC(50) from 8.8 to 55.9 microM.

PMID- 17454315
TI  - Triterpenoid saponins from Stauntonia chinensis.
AB  - A new triterpenoid saponin, named stauntoside A (1) along with four known
      saponins (2,3,4,5) was isolated from Stauntonia chinensis DC., (Lardizabalaceae).
      Their structures were elucidated by spectroscopic analysis and chemical methods
      as 3-O-alpha-L-arabinopyranosyl-30-norhederagenin -28-O-beta-D-glucopyranosyl-(1 
      -> 6)-beta-D-glucopyranosyl ester (1), 3-O-alpha-L-arabinopyranosyl-30-
      norhederagenin-28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 -
      > 6)-beta-D-glucopyranosyl ester (2), 3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-alpha
      L-arabinopyranosyl-30-norhederagenin-28-O-alpha-L- rhamnopyranosyl-(1 --> 4)-beta
      D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl ester (3), 3-O-alpha-L-
      arabinopyranosyl-hederagenin-28-O-alpha-L-rhamnopyranosyl-(1 --> 4)-beta-D
      glucopyranosyl-(1 --> 6)-beta-D- glucopyranosyl ester (4), 3-O-alpha-L
      rhamnopyranosyl-(1 --> 2)-alpha-L-arabinopyranosyl-hederagenin -28-O-alpha-L
      rhamnopyranosyl-(1 --> 4)-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranosyl
      ester (5). The (1)H and (13)C NMR data for Glycoside L-G1 or Sinofoside A are
      paradox in the reported before. Thus, the structure elucidation of saponin 2,
      known as Glycoside L-G1 or Sinofoside A, was discussed and the unambiguous
      assignments were given.

PMID- 17454316
TI  - A novel alkaloid from Gaultheria nummularioides.
AB  - A novel alkaloid, gaultherialine A (1), along with twenty-seven known compounds
      were isolated from the whole plants of Gaultheria nummularioides D. Don. The
      structure of the new alkaloid was elucidated as 7,8-dimethoxy-1-(4-methoxyphenyl)
      4,5-dihydro-2H-benzo[e]indole-2-one N-oxide (1) on the basis of spectral
      evidence.

PMID- 17454317
TI  - A new cucurbitacin from Bolbostemma paniculatum Franguent.
AB  - A new cucurbitacin with an unusual ring A, isocucurbitacin D 25-O-acetate (1),
      was isolated from Bolbostemma paniculatum Franguent together with one known
      compound, cucurbitacin E (2). The structure of new compound was established by
      spectroscopic methods.

PMID- 17454318
TI  - Effect of maternal asthma and gestational asthma therapy on fetal growth.
AB  - Asthma is a common chronic condition that might seriously complicate pregnancy
      and fetal development. This article provides a comprehensive review of the
      existing literature regarding the effect on fetal growth of maternal asthma and
      common asthma medications used during pregnancy, including short-and long-acting
      beta (2)-agonists, inhaled and oral corticosteroids, chromones, leukotriene
      receptor agonists, and theophylline. Evaluated outcomes of fetal growth include
      low birth weight, mean birth weight, small for gestational age, birth length and
      head circumference, and measures of asymmetrical growth retardation.
      Methodological and practical considerations related to safety of asthma
      medications in pregnancy and management of gestational asthma are discussed.

PMID- 17454319
TI  - Addition of transdermal or inhaled long-acting Beta2-agonists in adult asthmatic
      patients treated with inhaled corticosteroids: switchover study from tulobuterol
      patch to salmeterol dry powder inhaler.
AB  - Sixty-four patients with persistent asthma receiving 200 to 800 microg of
      fluticasone propionate daily were enrolled in this switchover study. The patients
      applied a tulobuterol patch 2 mg every 24 hours for 4 weeks followed by
      inhalation of salmeterol 100 microg bid for 4 weeks. The mean values for morning
      and evening peak expiratory flow improved significantly compared with baseline
      during the 4 weeks of tulobuterol patch treatment. Further improvement was seen
      on switching to salmeterol treatment, which was significant even in the first
      week, and continued until the final week of the study. Use of salmeterol alone
      resulted in a significant increase in the percentage of forced expiratory volume
      in 1 second %FEV1 from baseline, with 51% of patients feeling that the treatment
      was effective (vs. 37% on tulobuterol). These data suggest that salmeterol can
      achieve better control in asthmatic patients after switching from using
      tulobuterol patches.

PMID- 17454320
TI  - Barriers to reducing ETS in the homes of inner-city children with asthma.
AB  - This study assessed knowledge regarding the harm of environmental tobacco smoke
      (ETS) exposure and barriers to reducing ETS from the point-of-view of urban
      parents of asthmatic children. We conducted in-depth interviews with 15 mothers
      of children with asthma. All parents had good knowledge regarding the harmful
      effects of ETS. While all children of smoking parents were exposed to ETS,
      parents described using various strategies to keep ETS away from children. Many
      parents experienced significant stress in their lives and used smoking to relieve
      their stress. Barriers to a smoke-free home included stress, addiction, and the
      use of ineffective strategies to reduce ETS exposure.

PMID- 17454321
TI  - The frequency of wheezing phenotypes and risk factors for persistence in aegean
      region of Turkey.
AB  - The aim of the study was to determine the prevalence of wheezing and evaluate the
      risk factors for its persistence in children. Survey data was collected on 725
      children aged 17 years or below. The mean age was 8.94 +/- 5.16 years; 22.1% of
      them were reported to have had a wheezing episode at any point in their lives. A
      wheezing episode was reported in 18.1% of children 3 years of age or younger and
      persisted in 51% of these subjects; 69.6% of ever wheezers had late onset
      wheezing. Persistence was significantly common in males. Perinatal disease, lack
      of breast feeding, and low income were significant risk factors for persistence.
      In summary, breast feeding, perinatal disease, and income status may be
      significant risk factors influencing wheezing peristence and consequent asthma.

PMID- 17454322
TI  - Patient, home residence, and neighborhood characteristics in pediatric emergency
      department visits for asthma.
AB  - OBJECTIVE: To identify patient, home residence, and neighborhood characteristics
      of children with asthma-related emergency department visits. METHODS: Medical
      records of children with one (group A) or more than one (group B) asthma-related
      pediatric emergency department visit were reviewed. RESULTS: A significantly
      higher percentage of group B had Medicaid insurance (p = 0.04), history of asthma
      related hospitalizations (p = 0.04), and passive tobacco smoke exposure (p =
      0.03). Neighborhood characteristics were similar between the two groups.
      CONCLUSIONS: Smoking cessation counseling and close monitoring of patients with a
      history of asthma-related hospitalizations and patients with Medicaid insurance
      may be helpful in decreasing emergency department visits.

PMID- 17454323
TI  - Cow's milk exposure and asthma in a newborn cohort: repeated ascertainment
      indicates reverse causation.
AB  - The effect of cow's milk consumption on childhood asthma has been debated for
      several years. This study attempts to provide further insight into this
      association through the use of a longitudinal study design. Newborns from parents
      with atopic history were recruited from Germany, Austria, and England (n = 696).
      For five repeated ascertainments, information was collected on cow's milk
      exposure, incidence of doctor-diagnosed asthma, and confounders. Generalized
      estimation equations, incorporating different models (concurrent, delayed,
      combined, and reverse causation), were used to determine this association. No
      association between cow's milk consumption and childhood asthma was found for the
      concurrent effects model (OR = 0.81, 95% confidence interval [CI]: 0.55, 1.20).
      In the delayed effects model, the direction of the association varied with time
      of follow-up. Thus, we stratified by period, which resulted in a significant
      protective delayed effect at 36 months (OR = 0.18, 95% CI = 0.06, 0.49). However,
      reverse causation negated this finding since the presence of asthma in prior
      months led to a reduction in further exposure to cow's milk (OR = 0.40, 95% CI =
      0.16, 0.99). Hence, cow's milk consumption does not protect against childhood
      asthma. The apparent protection of cow's milk against asthma may result from
      parents of asthmatic children avoiding cow's milk, rather than actual
      prophylaxis.

PMID- 17454324
TI  - QUOTAC: QUestionnaire On day and night Time respiratory symptoms in Asthmatic
      Children -- a validity study.
AB  - The aim of this study was to validate the QUOTAC, a questionnaire on day and
      night time respiratory symptoms in asthmatic children. Validity was examined by
      measuring agreement between the QUOTAC and a self-report diary in children aged 6
      to 16 years, divided in an asthma group and a control group. As an extra interest
      in our study a sum score was computed as a measure of the severity of asthma.
      This study shows that the QUOTAC is discriminative between asthmatic and healthy
      children and is a reliable and sensitive scale for measuring the severity of
      asthma. However, cut-off scores for mild, moderate, or severe asthma should be
      investigated in further research.

PMID- 17454325
TI  - Success of a comprehensive school-based asthma intervention on clinical markers
      and resource utilization for inner-city children with asthma in Chicago: the
      Mobile C.A.R.E. Foundation's asthma management program.
AB  - Children with asthma in low-income households in Chicago were participants in a
      school-based mobile van clinic, Mobile C.A.R.E. Our objective was to investigate
      whether long-term follow-up changed clinical markers and resource utilization.
      Children were evaluated by a pediatrician in a mobile allergy clinic and
      classified and treated based on National Asthma Education and Prevention Program
      (NAEPP) guidelines. Intervention consisted of assessment of allergic environment
      with avoidance recommendations, institution of appropriate controller therapy and
      inhaler technique, education on asthma and asthma management, and expectations
      for asthma control. Over 20,000 children were screened, 2041 were examined at
      least once, and 677 children had four follow-up visits. With follow-up, there was
      a decrease in hospitalizations and emergency room visits. Symptomatic markers
      (daytime and nighttime cough, wheezing, and dyspnea symptoms), frequency of
      rescue inhaler use, and a quality-of-life score improved from baseline. These
      findings suggest that ongoing school interventions may reduce resource
      utilization and improve clinical symptoms. Primary care physicians may be able to
      deliver specialized care to large numbers of inner-city children with asthma.

PMID- 17454326
TI  - Psychological, academic, and work functioning in college students with childhood
      onset asthma.
AB  - This study investigated differences in psychological, academic, and work
      functioning between college students with and without asthma and identified
      predictors of functioning. Both participants with asthma (n = 121) and age-and
      gender-matched healthy control subjects (n = 121) completed measures of
      psychological distress, provided information on missed school and work days, and
      consented to have their grade point averages released from the registrar. College
      students with asthma also completed measures of illness uncertainty and illness
      intrusiveness. Participants with asthma reported greater anxiety, general
      psychological distress, and more missed school and work days compared to healthy
      control subjects. Within the asthma group, both illness uncertainty and illness
      intrusiveness independently predicted anxious and depressive symptoms and general
      psychological distress; illness intrusiveness also predicted missed school days.
      Although enrollment in college implies resilient functioning, college students
      with asthma remain at risk for problems with psychological and academic
      functioning.

PMID- 17454327
TI  - Health-related quality of life in children with asthma from different ethnic
      origins.
AB  - This study aimed to identify and explain differences in health-related quality of
      life (QoL) between immigrant and non-immigrant children with asthma. In 274
      children (7-17 years of age) generic and asthma-related QoL were assessed. The
      association between ethnicity and QoL was studied in linear regression model
      analyses. For the asthma-related QoL, unadjusted analyses showed significant
      ethnic differences. The non-immigrant children had the highest scores, which
      implies a better QoL. After adjusting for asthma control and socioeconomic status
      (SES), ethnic differences disappeared. These results suggest that immigrant
      children have a similar QoL to that of non-immigrant children from a comparable
      SES, when their asthma is under control.

PMID- 17454328
TI  - Asthma mortality in southern Brazil: is there a changing trend?
AB  - BACKGROUND: Mortality from asthma increased during the last decades but is now
      declining in some countries. Little is known about this trend in Brazil.
      OBJECTIVE: The objective of the study was to determine the trends in asthma
      mortality in Southern Brazil. METHODS: We reviewed death certificates of 566
      people in the state of Rio Grande do Sul, Brazil, between 5 and 39 years of age
      in whom asthma was reported to be the underlying cause of death during the period
      of 1981-2003. Population data were available in 5-year age groups. Mortality
      rates were submitted to linear and quadratic regression procedures. RESULTS:
      Among children and teenagers (5-19 years), there were 170 asthma deaths, ranging
      from 4 to 13 deaths each year with rates of 0.154/100,000 to 0.481/100,000. In
      young adults (20-39 years), 396 asthma deaths occurred, ranging from 9 to 32 each
      year, with rates from 0.276/100,000 to 1.034/100,000. There was an initial
      increase in rates, with later stabilization, and then the start of a decline
      beginning in the late 1990s and the early part of this decade. This trend
      occurred in both age subgroups examined but was more evident in males.
      CONCLUSIONS: Asthma mortality in southern Brazil remains low and appears to be
      decreasing after reaching a peak in the mid-1990s. The reason for these trends
      remains unknown.

PMID- 17454329
TI  - Improved health outcomes with peak flow monitoring for children with asthma.
AB  - PURPOSE: Evaluate the effects of peak flow monitoring (PFM) on health outcomes of
      school-age children with asthma. METHOD AND SAMPLE: Seventy-seven children who
      previously relied on symptom monitoring were taught PFM. Adherence to PFM during
      the 16-week study was assessed by a computerized monitor. Health outcomes over
      time were based on parent report. RESULTS: Decreases occurred from baseline to
      week 16 in the incidence of one or more asthma episodes (p = 0.0002),
      physician/clinic visits (p = 0.0002), emergency department visits (p = 0.03), and
      missed school days (p = 0.002). CONCLUSIONS: PFM significantly reduced pediatric
      asthma morbidity in this sample.

PMID- 17454330
TI  - Cold air and exercise challenge -- influence of minute ventilation.
AB  - Exercises testing and cold air challenges are frequently used to assess airway
      hyperresponsiveness (AHR), but different goals are set for the two tests. We,
      therefore, wished to determine whether cold air and exercise challenge testing
      yielded similar responses and if any differences were due to differences in the
      maximum minute ventilation achieved. Twenty asthmatic subjects each performed a
      cold air (CACh) and an exercise (EXCh) challenge. Baseline forced expiratory
      volume in one second (FEV(1)) was recorded immediately pre-challenge and then
      serially for at least 10 minutes post-challenge. The maximum minute ventilation
      achieved was recorded. In the subjects who had at least a decrease in FEV(1) of
      15% in response to the first CACh, a second CACh was performed, but at the
      maximum minute ventilation achieved during EXCh. Eleven subjects after CACh and
      four after EXCh had a greater than 15% decrease in FEV(1) (p = 0.05). The median
      decrease in FEV(1) was greater following the CACh (16.7%[25th to 75th percentile
      10.4 to 19.9]) than the EXCh (6.9%[25th to 75th percentile 4.3 to 14.6]); (p =
      0.0004). The median maximum minute ventilation achieved was greater with the CACh
      (89[66-141] L/min) than with the EXCh (61(40 to 102)L/min); (p < 0.0001). Only
      one of seven subjects who had previously responded to the CACh had a 15% decrease
      in FEV(1) when the CACh was repeated at the same maximum minute ventilation
      achieved during EXCh (p = 0.007). In conclusion, cold air and exercise challenges
      do not produce the same response. Our results highlight than an explanation is
      the differences in the maximum-minimum ventilation achieved.

PMID- 17454331
TI  - The impact of comorbid atopic disease on asthma: clinical expression and
      treatment.
AB  - Clinically, asthma and allergic rhinitis involve separate regions of the
      respiratory tract while representing a common underlying inflammatory syndrome.
      Much evidence supports an epidemiologic association between the diseases,
      paranasal sinus involvement in both conditions, and parallel relationship in
      severity and treatment outcomes. Pathophysiologic mechanisms, including
      immunoglobulin E (IgE)- mediated inflammation, are also shared. Blocking IgE with
      the recombinant humanized monoclonal antibody omalizumab demonstrated clinical
      efficacy in patients with upper and lower airway diseases. IgE blockade,
      leukotriene modulation, and B-cell depletion therapy have all exhibited success
      in chronic inflammation, reinforcing and expanding the beneficial role of
      immunomodulation of global mediators.

PMID- 17454332
TI  - Severity of childhood asthma and human leukocyte antigens type.
AB  - We sought to learn if Class II HLA genes are associated with the severity of
      asthma in children. We examined a previously recruited cohort of 340 healthy
      children who had Class II HLA allele data available. We conducted a comprehensive
      review of their medical records to determine asthma status and, when present, its
      severity. We found that Class II HLA alleles, which were previously reported to
      have an association with asthma incidence, appear to have an association as well
      with asthma severity. These data support our hypothesis that both the incidence
      and severity of asthma are heritable and that HLA may play an important role in
      both development and severity of asthma. Because of limited statistical power,
      our study findings are subject to further investigation.

PMID- 17454333
TI  - Complementary and alternative medicine use in children with asthma: prevalence
      and sociodemographic profile of users.
AB  - Research on complementary and alternative medicine use in children with asthma is
      in its infancy. This study examined the prevalence, types of CAM used and
      sociodemographic differences in CAM use among children 5-12 years with asthma.
      65% of parents reported using CAM. Usage was highest among black, poor, lesser
      educated parents and children with persistent symptoms. Types of CAM differed by
      poverty and a trend for differences by race and education emerged. Health care
      providers who educate themselves on CAM therapies parents use for asthma can then
      discuss the implications of using these therapies and potentially improve
      adherence to the prescribed medication regimen.

PMID- 17454334
TI  - Can older adult volunteers serve effectively to improve asthma management for
      children? Experience Corps Baltimore.
AB  - The present study was conducted to determine whether older adults can learn and
      retain information on asthma and play a role as community health workers to teach
      children about asthma. A total of 36 older adults and 28 students in grades K-6
      participated. Pre-tests and post-tests were administered to participants.
      Improvement in older adult scores after training was significant (p = .001), and
      improvement persisted through the conclusion of teaching sessions (p = 0.001).
      The increase in lower student scores was significant (p = 0.050). Results suggest
      that older adults can learn and retain asthma information and schoolchildren can
      learn asthma-related information taught by older adults.

PMID- 17454335
TI  - Impact of home environment characteristics on asthma quality of life and symptom
      scores.
AB  - We explore the relationship between home-based triggers, asthma symptoms, and
      quality of life (QOL) with data from 177 adult and pediatric participants who
      received a home environmental assessment. Outcomes included the Asthma Quality of
      life Questionnaire, the Prediatric Asthma Quality of Life Questionnaire, the
      Paediatric Asthma Caregiver's Quality of Questionnaires and the Lara Asthma
      Symptom Scale. The absence of roaches and the use of dust mite covers were
      positively associated with QOL in pediatric and adult participants. Frequent bed
      sheet washing was associated with increased symptoms and decreased quality of
      life in adults and caregivers of pediatric participants. These findings confirm
      existing wisdom on roaches and dust mite covers and raise important questions
      about bed sheet washing recommendations.

PMID- 17454336
TI  - Agreement between caregiver reported healthcare utilization and administrative
      data for children with asthma.
AB  - In asthma, healthcare utilization is frequently an outcome measure and can come
      from several sources. Asthma-related hospitalizations, emergency department (ED)
      visits, oral steroid bursts, and outpatient visits were compared between
      caregiver report and administrative data over 2 years. The difference between
      sources (caregiver minus administrative) was as follows: hospitalizations = -0.02
      (95% limits of agreement, -0.66 to 0.61), ED visits = 0.18 (-1.16 to 1.52),
      steroid bursts = 0.26 (-3.98 to 4.49), and outpatient visits = 0.29 (-6.10 to
      6.64). The percent of individuals with disagreement between sources was
      hospitalizations = 6.1%; ED visits = 20.2%; steroid bursts = 34.3%; and
      outpatient visits = 83.6%. The data sources resulted in similar estimates on the
      population level; however, there were pronounced differences for outpatient
      visits on an individual level. Importantly, the individual level disagreement
      between the data sources could negatively affect the perceived quality of care
      provided by a physician and reduce their compensation in a pay-for-performance
      system when physicians are rated using administrative data, yet they provide
      treatment based on patient-reported information.

PMID- 17454337
TI  - Home therapy with subcutaneous anti-immunoglobulin-E antibody omalizumab in 25
      patients with immunoglobulin-E-mediated (allergic) asthma.

PMID- 17454338
TI  - Impact of traffic flow on the asthma prevalence among school children in Lima,
      Peru.
AB  - OBJECTIVE: To estimate the impact of traffic flow on the prevalence of asthma
      among school children of 6 to 7 and 13 to 14-years of age. METHODS: A cross
      sectional study consisting of 5,917 children selected in schools of the Cone
      Norte of Lima, Peru. RESULTS: For the 6- to 7-year age group the prevalence of
      medical diagnosis of asthma according to the traffic flow index was 8.6% (CI: 6.8
      10.8), 10.3% (CI: 8.4-12.4), and 15.3% (CI:13.3-17.5) at low, medium and high,
      respectively, and for the 13- to 14-year age group, 11.9% (CI: 9.4-14.6), 13.3%
      (CI: 11.6-15.2), and 17.1% (CI: 14.7-19.6). CONCLUSIONS: For both groups, the
      prevalence of asthma was significantly related to traffic flow density.

PMID- 17454339
TI  - Psychopathology and personality factors modify the perception of dyspnea in
      asthmatics.
AB  - We studied the relationship between the intensity of dyspnea and
      psychopathological and personality dimensions in 74 women and 38 men (mean age
      49.7 years) with asthma. The women had higher values for the following variables:
      depression, anxiety-trait, and neuroticism, and they proved to have a greater
      external control location than the men. After checking the spirometry results,
      body mass index (BMI) and gender, it was found that dyspnea correlated with
      anxiety-trait and anxiety-state, neuroticism, and depression. In the men, anxiety
      trait modified the relationship between dyspnea and the duration of the disease.
      This effect was not found in the women. A high level of anxiety-trait seems to be
      responsible for the escalation of dyspnea during the progression of the disease
      in men, whereas low anxiety may protect them against the increase of dyspnea.
      FEV(1), BMI, and anxiety-trait were predictors of dyspnea.

PMID- 17454340
TI  - Monitoring flow rates and retention of inhalation techniques using the in-check
      dial device in adult asthmatics.
AB  - The In-Check-Dial (Alliance Tech Medical, Granburg, TX) was used to determine
      adequacy of inhalation techniques and teaching of two different devices.
      Retention of adequate techniques, was assessed in 234 moderate to severe
      asthmatics. Inhalation techniques were assessed at periodic follow-ups divided
      into less than 1 month return visit, between 1 and 3 months, 3 to less than 6
      months, and 6 months to less than 1 year. Proper inhalation techniques worsened
      at greater than 3 months after the last instruction. The use of the In-Check-Dial
      is a useful tool in teaching proper technique and monitoring the patient's
      ability to correctly use inhalation devices.

PMID- 17454341
TI  - Protection against exercise-induced bronchoconstriction two hours after a single
      oral dose of montelukast.
AB  - The objective of this double-blind cross-over study was to evaluate montelukast
      for the prevention of exercise-induced bronchoconstriction (EIB). Sixty-two
      patients with EIB (post-exercise decrease in forced expiratory volume in 1 second
      (FEV(1)) > or = 20% at pre-randomization) were randomized to montelukast 10 mg or
      placebo, followed by exercise-challenge 2, 12, and 24 hours postdose. The primary
      endpoint was the maximum percent-fall in FEV(1) (from pre-exercise FEV(1)) during
      60 minutes after exercise-challenge at 2 hours postdose. This endpoint was
      improved after montelukast (mean +/- SD = 11.7% +/- 10.8) versus placebo (17.5%
      +/- 13.8) (p < or = 0.001); numerically greater improvements were seen at 12
      hours and 24 hours. A quicker time to recovery after challenge (p < or = 0.001)
      and a smaller area under the curve for percent-fall in FEV(1) during 60 minutes
      after challenge (p < or = 0.01) were seen with montelukast at 2 hours. At this
      timepoint, more patients taking montelukast (45/54) than taking placebo (37/54)
      were protected against EIB (p = 0.039). We concluded that montelukast provided
      significant protection against EIB at 2 hours after a single dose.

PMID- 17454342
TI  - Psycho-educational interventions for adults with severe or difficult asthma: a
      systematic review.
AB  - Research highlights psychosocial factors associated with adverse asthma events.
      This systematic review therefore examined whether psycho-educational
      interventions improve health and self-management outcomes in adults with severe
      or difficult asthma. Seventeen controlled studies were included. Characteristics
      and content of interventions varied even within broad types. Study quality was
      generally poor and several studies were small. Any positive effects observed from
      qualitative and quantitative syntheses were mainly short term and, in planned
      subgroup analyses (involving < 5 trials), effects on hospitalizations, quality of
      life, and psychological morbidity in patients with severe asthma did not extend
      to those in whom multiple factors complicate management.

PMID- 17454344
TI  - The nonintentional processing of Arabic numbers in children.
AB  - This paper aims at determining when magnitude is automatically activated from
      Arabic digits in children and whether this automatic activation depends on the
      number size of the stimuli considered. Second, third, and fourth graders
      performed a physical Stroop task in which pairs of single- and two-digit Arabic
      numerals in a ratio 1:2 or 2:3 were used. In addition, the speed of perceptual
      and semantic information was balanced: Instead of presenting the two members of
      each pair directly with a physical size difference, they first appeared in the
      same intermediate physical size, the perceptual difference occurring only after
      some time. The results indicated a significant effect of congruity at all grades,
      with faster reaction times and lower error rates for congruent trials than for
      incongruent trials, for both one- and two-digit numerals. Furthermore, this
      congruity effect was affected by the ratio of the numbers in the pairs. Only
      pairs of ratio 1:2 were affected by this congruity effect. These findings
      strongly support the fact that children as young as 7 years old can automatically
      access the magnitude information of one- as well as two-digit Arabic numerals.

PMID- 17454345
TI  - Attention, inhibition, and proximity to clinical onset in preclinical mutation
      carriers for Huntington's disease.
AB  - Research in preclinical mutation carriers for Huntington's disease (HD) aims to
      find measures sensitive to preclinical decline. This study investigated
      attentional abilities in mutation carriers and noncarriers. Mutation carriers
      demonstrated a normal "attentional blink" during rapid serial visual
      presentation, normal covert visual orienting, and normal directing of attention
      to tactile stimuli. However, they were more likely than noncarriers to make
      anticipatory responses before target presentation. Additionally, those closer to
      estimated onset of HD demonstrated larger "inhibition of return" effects. The
      findings suggest potential changes in cognitive inhibition of unwanted responses,
      and in automatic inhibition of visual orienting, in preclinical HD.

PMID- 17454346
TI  - Cortical activation during word processing in late bilinguals: similarities and
      differences as revealed by functional magnetic resonance imaging.
AB  - Functional magnetic resonance imaging was used to compare cortical organization
      of the first (L1, Russian) and second (L2, English) languages. Six fluent Russian
      English bilinguals who acquired their second language postpuberty were tested
      with words and nonwords presented either auditorily or visually. Results showed
      that both languages activated similar cortical networks, including the inferior
      frontal, middle frontal, superior temporal, middle temporal, angular, and
      supramarginal gyri. Within the inferior frontal gyrus (IFG), L2 activated a
      larger cortical volume than L1 during lexical and phonological processing. For
      both languages, the left IFG was more active than the right IFG during lexical
      processing. Within the left IFG, the distance between centers of activation
      associated with lexical processing of translation equivalents across languages
      was larger than the distance between centers of activation associated with
      lexical processing of different words in the same language. Results of
      phonological processing analyses revealed different centers of activation
      associated with the first versus the second language in the IFG, but not in the
      superior temporal gyrus (STG). These findings are discussed within the context of
      the current literature on cortical organization in bilinguals and suggest
      variation in bilingual cortical activation associated with lexical, phonological,
      and orthographic processing.

PMID- 17454347
TI  - The impact of neuropsychological functioning and depressed mood on functional
      complaints in HIV-1 infection and methamphetamine dependence.
AB  - Diagnosis of neurobehavioral syndromes associated with HIV infection requires the
      determination that neuropsychological (NP) deficits are present, are not caused
      by any comorbid (e.g., psychiatric) condition, and significantly affect everyday
      functioning. Methamphetamine (Meth) dependence and depression are common comorbid
      conditions with HIV and may complicate diagnosis of HIV-associated
      neurobehavioral syndromes. The current study examined the complex relationships
      between depression and NP impairment, and self-report of problems with everyday
      functioning, in 362 adults with HIV infection or Meth dependence, or both.
      Everyday functioning was measured with questionnaires of instrumental activities
      of daily living (IADLs) and reported cognitive difficulties. Results indicate
      that comorbid HIV and Meth did not increase the likelihood of complaints
      regarding everyday functioning, beyond what was seen with either single risk
      factor. Across all groups, depressive symptoms predicted greater IADL decline and
      cognitive complaints, while NP impairment predicted cognitive complaints more
      than IADL decline. Both IADL decline and cognitive complaints were associated
      with higher rates of unemployment and worse clinician ratings of overall
      functioning (Karnofsky ratings), even when depressive symptoms were controlled.
      These results suggest that depressive symptoms should not be used to dismiss
      subjective complaints related to everyday functioning even though depressive
      symptoms account for significant variance in self-reported complaints. Additional
      research is needed to clarify the potentially reciprocal causal relationships
      between depressive symptoms and impairment in everyday functioning.

PMID- 17454348
TI  - Reaction time performance in adolescents with attention deficit/hyperactivity
      disorder: evidence of inconsistency in the fast and slow portions of the RT
      distribution.
AB  - Inconsistency across trials of 2-choice reaction time (RT) data was analyzed in
      72 adolescents (age 12-17 years) within 4 groups differentiated by the presence
      or absence of attention deficit/hyperactivity disorder (ADHD) and reading
      difficulties (RD). ADHD participants were more inconsistent (across all trials,
      and in the slow portion of the RT distribution) than controls, but only when RD
      was present. Within the fast portion of the RT distribution, ADHD participants
      were more inconsistent than controls regardless of RD. The results highlight the
      importance of fluctuations in cognitive performance in ADHD and suggest that
      there may be independent sources of variation in inconsistency affecting the fast
      and slow portions of the RT distribution.

PMID- 17454349
TI  - Neuropsychological data in nondemented oldest old: the 90+ Study.
AB  - Although the oldest old are the fastest growing segment of the population, little
      is known about their cognitive performance. Our aim was to compile a relatively
      brief test battery that could be completed by a majority of individuals aged 90
      or over, compensates for sensory losses, and incorporates previously validated,
      standardized, and accessible instruments. Means, standard deviations, and
      percentiles for 10 neuropsychological tests covering multiple cognitive domains
      are reported for 339 nondemented members of the 90+ Study. Cognitive performance
      declined with age for two-thirds of the tests. Performance on some tests was also
      affected by gender, education, and depression scores.

PMID- 17454350
TI  - The use of amnestic and nonamnestic composite measures at different thresholds in
      the neuropsychological diagnosis of MCI.
AB  - Both amnestic and nonamnestic deficits have been observed in patients with mild
      cognitive impairment (MCI). Most studies have focused on impairment on single
      cognitive tests rather than amalgamation of the results of several measures to
      arrive at a composite impairment index. In this investigation, we examined 20 MCI
      patients diagnosed as prodromal Alzheimer's disease, AD (mean Mini-Mental State
      Examination, MMSE = 26.1; SD = 1.7) and determined the extent to which they could
      be differentiated from 70 normal elderly controls based on composite measures at
      1.5-SD and 2.0-SD cutoffs for impairment. At the 1.5-SD cutoff, the median number
      of memory indices impaired in the MCI-AD group was 5 of 7, whereas at the 2.0-SD
      cutoff, the median number was 4 of 7. A median of 3 of 7 and 2 of 7 nonmemory
      indices were impaired at 1.5- and 2.0-SD cutoffs for impairment. Receiver
      operator characteristics (ROC) analyses indicated that the total number of memory
      tests impaired at 2.0 SD (sensitivity = 95.0%/specificity = 84.3%) and the
      composite measure of both impaired memory and nonmemory measures (sensitivity of
      85.0%/specificity of 100%) had high levels of discrimination and may have utility
      as indices of early impairment as well as severity of MCI.

PMID- 17454351
TI  - On the limits of effort testing: symptom validity tests and severity of
      neurocognitive symptoms in nonlitigant patients.
AB  - Modern symptom validity tests (SVTs) use empirical cutoffs for decision making.
      However, limits to the applicability of these cutoffs may arise when severe
      cognitive symptoms are present. The purpose of the studies presented here was to
      explore these limits of applicability. In Experiment 1, a group of 24 bona fide
      neurological patients without clinically obvious cognitive symptoms was compared
      to a group of 24 patients with rather severe symptoms. A comprehensive test
      battery was employed, which included four SVTs (the Test of Memory Malingering,
      TOMM, the Word Memory Test, WMT, the Bremer Symptomvalidierung, BSV, and the
      Amsterdam Short-Term Memory Test, ASTM). In Experiment 2, a group of 20 patients
      with mild Alzheimer's disease was compared to 14 healthy controls. Results of
      both studies showed that cognitive impairment may significantly interfere with
      SVT performance. Correlation analyses revealed dissimilar relationships between
      SVTs and neuropsychological test measures. Whereas TOMM and WMT correlated mainly
      with tests of declarative memory, the BSV correlated with tests of attention, and
      ASTM correlated with tests of working memory. Intercorrelations between symptom
      validity measures were relatively low. The published cutoffs of the TOMM would be
      suitable for estimating effort in patients with Mini-Mental State Examination
      scores of 24 or above. More research will be necessary to investigate how
      performance in SVTs is related to cognitive functioning in populations of
      severely impaired patients.

PMID- 17454352
TI  - Impaired behavior on real-world tasks following damage to the ventromedial
      prefrontal cortex.
AB  - Patients with damage to the ventromedial prefrontal cortices (VMPC) commonly
      manifest blatant behavioral navigation defects in the real world, but it has been
      difficult to measure these impairments in the clinic or laboratory. Using a set
      of "strategy application" tasks, which were designed by Shallice and Burgess
      (1991) to be ecologically valid for detecting executive dysfunction, we
      investigated the hypothesis that VMPC damage would be associated with defective
      performance on such tasks, whereas damage outside the VMPC region would not. A
      group of 9 patients with bilateral VMPC damage was contrasted with comparison
      groups of participants with (a) prefrontal brain damage outside the VMPC region
      (n = 8); (b) nonprefrontal brain damage (n = 17); and (c) no brain damage (n =
      20). We found support for the hypothesis: VMPC patients had more impaired
      performances on the strategy application tasks, especially on a Multiple Errands
      Test that required patients to execute a series of unstructured tasks in a real
      world setting (shopping mall). The results are consistent with the notion that
      efficacious behavioral navigation is dependent on the VMPC region. However, the
      strategy application tasks were relatively time consuming and effortful, and
      their diagnostic yield over and above conventional executive functioning tests
      may not be sufficient to warrant their inclusion in standard clinical assessment.

PMID- 17454353
TI  - The Tower of London: a study of the effect of problem structure on planning.
AB  - Only recently has there been any consideration of the influence of the problem
      structure on Tower of London task (TOL) performance. Not surprisingly, these few
      studies that have investigated this issue have found significant differences in
      the cognitive demands of individual TOL problems. Based on these previous
      findings, the aim of the current study was to further explore the effects of two
      problem characteristics on the planning process - namely, goal hierarchy and the
      number of optimal solution paths. A number of performance measures when solving
      six-move problems were examined, including preplanning time, movement time, and
      accuracy. Analysis of the preplanning time revealed that it was significantly
      affected by goal hierarchy but not the number of solution paths. The individual
      movement times, however, revealed effects for both goal hierarchy and the number
      of optimal solution paths. The number of paths only affected movement times at
      specific moves: those corresponding to the initiation of a subgoal chunk. The
      results are discussed in terms of the influence of preplanning on subsequent
      performance. The present study also suggests that greater care be taken in the
      selection of TOL problems.

PMID- 17454354
TI  - Targeted nanoparticle-based drug delivery and diagnosis.
AB  - Nanotechnology, or systems/device manufacture at sizes generally ranging between
      1 and 100 nm, is a multidisciplinary scientific field undergoing explosive
      development. The genesis of nanotechnology can be traced to advances in medicine,
      communications, genomics and robotics. One of the greatest values of
      nanotechnology will be in the development of new and effective medical treatments
      (i.e. nanomedicine). This review focuses on the potential of nanomedicine as it
      relates to the development of nanoparticles for enabling and improving the
      targeted delivery of therapeutic and diagnostic agents. We highlight the use of
      nanoparticles for specific intra-compartmental analysis using the examples of
      delivery to malignant cancers, to the central nervous system, and across the
      gastrointestinal barriers.

PMID- 17454355
TI  - Non-viral methods for gene transfer towards osteosarcoma therapy.
AB  - Osteosarcoma, a class of cancer that originates from bone, afflicts mainly young
      people usually in their teenage years of life. Despite surgery and chemotherapy,
      the outlook for sufferers is not that positive, with a third of patients with
      metastatic disease not surviving past the 10-year mark. Like other neoplasms,
      other forms of therapeutics are being evaluated, and amongst these is gene
      therapy. This review discusses approaches for gene therapy of osteosarcoma using
      cationic liposomes and polyethylenimine in vivo. The field is still in its
      infancy as far as osteosarcoma is concerned and much more needs to be done to
      test its true potential as a feasible therapeutic modality.

PMID- 17454356
TI  - Poly(L-lactide-co-glycolide) nanospheres conjugated with a nuclear localization
      signal for delivery of plasmid DNA.
AB  - Polymeric nanospheres fabricated from biodegradable poly(lactide-co-glycolide)
      (PLGA) have been extensively investigated for applications in gene delivery. In
      this study, we show that the covalent conjugation of a nuclear localization
      signal (NLS, SV40 peptide) on PLGA nanospheres enhances the gene transfection
      efficiency. NLS conjugated PLGA copolymer was prepared by using a coupling
      reaction between maleimide-terminated PLGA copolymer and NLS in the presence of
      Imject maleimide conjugation buffer. PLGA nanospheres encapsulating plasmid
      (pDNA) were prepared by using a double emulsion-solvent evaporation method. The
      kinetics of in vitro release of pDNA from PLGA nanospheres was determined with UV
      in phosphate buffered saline (PBS). Gene transfection efficiency in human dermal
      fibroblasts was tested in vitro using nanospheres encapsulating the luciferase
      gene. The conjugation of the NLS peptide to the PLGA nanospheres could improve
      the nuclear localization and/or cellular uptake of PLGA nanosphere/pDNA
      constructs and thereby improve the transfection efficiency of a PLGA nanosphere
      gene delivery system. The pDNA was released from PLGA nanospheres over nine days.
      NLS conjugation enhanced the gene transfection efficiency in vitro by 1.2
      approximately 3.2-fold over 13 days. PLGA/pDNA nanospheres appeared to be
      superior to PEI/pDNA complexes for the long-term expression of pDNA. Furthermore,
      the level of the sustained gene expression of the PLGA nanospheres was enhanced
      by the conjugation of NLS to the PLGA nanospheres. This study showed that the NLS
      conjugation enhanced the gene transfection efficiency of the PLGA nanosphere gene
      delivery system in vitro and that the enhanced gene expression was sustained for
      at least 13 days.

PMID- 17454357
TI  - Synthesis and in vitro evaluation of N-nicotinoylglycyl-2-(5-fluorouracil-1-yl)
      D,L-glycine as a colon-specific prodrug of 5-fluorouracil.
AB  - N-Nicotinoylglycyl-2-(5-fluorouracil-1-yl)-D,L-glycine (NGFG) was synthesized as
      a colon-specific prodrug of 5-fluorouracil (5-FU) expecting that hydrolysis of
      nicotinoyl and glycyl moieties by microbial enzymes in the colon will give 2-(5
      fluorouracil-1-yl)-D,L-glycine, which releases 5-FU spontaneously. To in vitro
      evaluate colon targetability of NGFG, apparent partition coefficient and
      chemical/biochemical stability of NGFG in the contents or/and tissue of the
      various segments of the gastrointestinal tract were determined. Low partition
      coefficient and stability of NGFG in the upper intestinal condition suggested its
      delivery to the colon in intact form after oral administration. Incubation with
      rat cecal contents produced 5-FU and its metabolite about 16%. Structural
      modification to enhance amide hydrolysis, the rate determining step in NGFG
      bioactivation, is suggested.

PMID- 17454358
TI  - Development and characterization of amphotericin B bearing emulsomes for passive
      and active macrophage targeting.
AB  - The antifungal and antileishmanial agent amphotericin B (AmB) has been complexed
      with lipids to develop a less toxic formulation of AmB. Because lipid particles
      are phagocytized by the reticuloendothelial system, lipid associated AmB should
      be concentrated in infected macrophages of liver and spleen and be very effective
      against visceral leishmaniasis (VL) and systemic fungal infections. Therefore,
      AmB was formulated in trilaurin based nanosize lipid particles (emulsomes)
      stabilized by soya phosphatidylcholine (PC) as a new intravenous drug delivery
      system for macrophage targeting. Emulsomes were prepared by cast film technique
      followed by sonication to obtain particles of nanometric size range. Formulations
      were optimized for AmB to lipid ratio, sonication time and PC to trilaurin ratio.
      Emulsomes were modified by coating them with macrophage-specific ligand (O
      palmitoyl mannan, OPM). The surface modified emulsomes and their plain
      counterparts were characterised for size, shape, lamellarity and entrapment
      efficiency. Fluorescence microscopy study showed significant localization of
      plain and coated emulsomes inside the liver and spleen cells of golden hamsters.
      In vivo organ distribution studies in albino rats demonstrated that extent of
      accumulation of emulsome entrapped AmB in macrophage rich organs, particularly
      liver, spleen and lungs was significantly high when compared against the free
      drug (AmB-deoxycholate or AmB-Doc). The rate and extent of accumulation were
      found to increase further on ligand anchoring. Further, a significantly higher (P
      < 0.05) drug concentration in the liver was estimated over a period of 24 h for
      OPM coated emulsomes than for plain emulsomes. We concluded that OPM coated
      emulsomes could fuse with the macrophages of liver and spleen due to ligand
      receptor interaction and could target the bioactives inside them. The proposed
      plain and OPM coated emulsome based systems showed excellent potential for
      passive and active intramacrophage targeting, respectively and the approach could
      be a successful alternative to the currently available drug regimens of VL and
      systemic fungal infections.

PMID- 17454359
TI  - Cysteine scanning of transmembrane domain three of the human dipeptide
      transporter: implications for substrate transport.
AB  - The human intestinal dipeptide transporter (hPepT1) transports dipeptides and
      pharmacologically active drugs from the intestine to the blood. The role of
      transmembrane domain 3 (TMD3) of hPepT1 was studied using cysteine-scanning
      mutagenesis and methane thiosulfonate (MTS) cysteine modification. Each amino
      acid in TMD3 was individually mutated to a cysteine and Gly-Sar uptake by each
      mutated and modified transporter was determined relative to wild-type hPepT1.
      Uptake data for mutated transporters modified with the lipid-insoluble cysteine
      modifying reagent MTSET suggested tilting of TMD3 relative to the substrate
      translocation pathway; the extracellular region of TMD3 showed little MTSET
      reactivity, indicative of solvent inaccessibility, whereas the intracellular part
      of TMD3 was relatively solvent accessible. Modification at 10 positions of TMD3
      with MTSEA, a lipid-soluble cysteine-modifying reagent, gave unusual and
      statistically significant increases in Gly-Sar uptake relative to untreated
      mutants. We interpret these data in terms of the spatial properties of the hPepT1
      substrate translocation channel and possible interactions of TMD3 with other
      transmembrane domains.

PMID- 17454360
TI  - Gene delivery to brain cells with apoprotein E derived peptide conjugated to
      polylysine (apoEdp-PLL).
AB  - A promising strategy to carry genetic material to brain cells either in vitro or
      in vivo is using the LDL receptor (LDLr) on blood-brain barrier. LDLr naturally
      help to low density lipoproteins (LDL(S)) transporting across the BBB by
      endocytosis. Here we present the idea of using the LDLr-mediated pathway for
      transporting genetic material to brain cells. A tandem dimer Sequence of
      apoprotein-E (apoE) (141-150) conjugated to polylysine sequence was used as a
      novel DNA Delivery vector for transfecting of brain cells either in vitro or in
      vivo. DNA condensation occurs with this vector because electrostatic interaction
      between DNA and polylysine. The vector favors to protection of DNA from enzymatic
      degradation and also helps to DNA carrying in blood stream to reach BBB and
      transport it to brain cells and eventually help DNA expression in target cells.
      These results suggest a novel gene delivery vector for gene therapy of brain
      disease.

PMID- 17454361
TI  - Design and development of folate appended liposomes for enhanced delivery of 5-FU
      to tumor cells.
AB  - Folate appended sterically-stabilized liposomes (FA-SL) were investigated for
      tumor targeting. Liposomes were prepared using HSPC, cholesterol and FA
      polyethylene glycol (PEG)-SA. The liposomes with polyethylene glycol (PEG)
      without folic acid which has similar lipid composition were used for comparison.
      Liposomal preparations were characterized for shape, size and percent entrapment.
      The average size of liposomes was found to be in range 124-163 nm and maximum
      drug entrapment was found to be 34.2-40.3%. In vitro drug release from the
      formulations is obeying fickian release kinetics. Cellular uptake and IC(50)
      values of the FR-targeted formulation were determined in vitro in FR (+) B16F10
      melanoma cells. In vitro cell binding of FA-SL exhibits 11-folds higher binding
      to B16F10 melanoma cells in comparison to SL. In vivo cytotoxicy assay on FR
      targeted liposomes gave IC(50) of 1.87 microM and non-targeted liposomes gave
      IC(50) of 4.02 microM. In therapeutic experiments 5-fluorouracil (5-FU), SL and
      FA-SL were administered at the dose of 10 mg 5-FU/kg body weight to B16F10 tumor
      bearing Balb/c mice. Administration of FA-SL formulation results in effective
      reduction in tumor growth as compared with free 5-FU and SL. Results indicate
      that folic acid appended SL bearing 5-FU are significantly (P < 0.01) active
      against primary tumor and metastasis than non-targeted sterically-SL. Thus, it
      could be concluded that folate coupled liposomal formulations enhanced drug
      uptake by tumor cells.

PMID- 17454362
TI  - Study on the reduction of NH3 volatilization from broiler litter through the
      promotion of nitrification.
AB  - Under laboratory conditions we studied the possibility of decreasing NH(3)
      emissions from broiler litter by applying one of two nitrifier seeds (a material
      obtained from the top centimeters of the dirt floor of a chicken house, or
      Houston Black clay soil) at 0, 2.5, 5, and 10% w/w. Ammonia emission rates, total
      NH(3) trapped in 0.1N H(2)SO(4), and NO(x)(-)-N concentrations decreased at the
      highest application rate of either amendment, whereas CO(2) emissions increased
      with the amendments' application rates. We hypothesize that the lack of a
      significant increase in NO(x)(-)-N concentrations was due to inhibition of
      nitrifiers by high NH(4)(+)-N, salt and Cl(-) concentrations, and denitrification
      promoted by high water, availability of easily decomposable carbon sources, and
      limited O(2) supply.

PMID- 17454363
TI  - A diagnosis-prescription system for nitrogen management in environment.
AB  - A decision support system in the framework of the geographic information system
      (GIS) and subsurface flow model, Hydrosub, were used to identify critical areas
      from simulated spatial distributions of relative nitrogen export. Diagnosis and
      prescription Expert Systems (ES) are developed and applied to the identification
      of probable causes of excessive nitrogen export and selection of appropriate Best
      Management Practices (BMPs). The result is a spatially distributed set of
      recommended Best Management Practices that are feasible economically and
      environmentally. For the study watershed, using catch crops and rhizobium-legume
      (instead of using conventional commercial fertilizers) were the most recommended
      Best Management Practices.

PMID- 17454364
TI  - Diisobutyl phthalate degradation by Fenton treatment.
AB  - Degradation of diisobutyl phthalate (DIBP) by Fenton oxidation was evaluated in
      this study. The results indicate that the pH, H(2)O(2) and Fe(2 +) concentration
      were three main operating factors considerably affecting the decomposition of
      DIBP. The optimum conditions were observed at pH 3 and the molar ratio of
      [H(2)O(2)]: [Fe(2 +)]: [DIBP] = 5: 5: 1. Under such condition, the maximum
      removal of DIBP was as high as 87% at a time of 30 minutes. In general, the
      empirical equation was derived as follows: (dC(DIBP)/dt)(initial) = -k
      C(DIBP,0)(0.88)C(Fe2 +,0)(0.33)C(H2O2)(0.95).

PMID- 17454365
TI  - Quantitative structure-activity relationships for the prediction of relative in
      vitro potencies (REPs) for chloronaphthalenes.
AB  - Chloronaphthalenes (CNs), due to their structural similarities to 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and the other "dioxin-like" compounds, can
      bind to the aryl hydrocarbon receptor (AhR) and induce a wide range of
      pleotrophic effects. Relative potency of individual dioxin analogues can be
      measured relative to that of TCDD. Relative effects potencies (REP) can be based
      on many responses, including in vivo and in vitro responses. Both in vivo and in
      vitro tests, based on either indigenous responses such as the induction of
      ethoxyresorufin O-deethylase (EROD) or exogenous reporter genes under the control
      of the AhR such as luciferase can be used to determine REP values. Here we used
      measured REP values determined for CNs in two assays. Both assays are based on
      H4IIE rat hepatoma cells. The H4IIE assay is based on expression of the
      endogenous reporter gene (CYP-1 A) that codes for the expression of EROD and the
      H4IIE-luc assay which is based on the exogenous reporter gene (luciferase)
      transfected into the H4IIE cell line. Experimentally determined REP were
      available for only 17 and 18 of the 75 possible choronaphthalene congeners, for
      the H4IIE and H4IIE-luc assays, respectively. For this reason computational
      models were developed to allow prediction of the relative potencies of the other
      CN congeners. Predictive relationships were based on quantum chemical descriptors
      obtained from Density Functional Theory (DFT) calculations (B3LYP/6-311++G**).
      The final models were found by means of a hybrid method combining a genetic
      algorithm and artificial neural networks. REP values estimated for individual CNs
      based on the H4IIE assay ranged from 4.3 x 10(- 9) to 3.2 x 10(- 2) while those
      based on the H4IIE-luc assay ranged from 4.0 x 10(- 8) to 1.8 x 10(- 3). CN
      congeners nos. 66, 67, 70 and 73 were exhibited the greatest REP values in both
      assays. The 1,2,3,5,6,8-hexaCN congener (no. 68) had a REP value that was 10-fold
      less. The remaining congeners had REP values that were less or did not cause
      sufficient up-regulation of the monitored genes to allow for the calculation of a
      REP. Interactions of CNs with the AhR could be affected by three possible
      factors: molecular size, steric interactions and electrostatic interactions.
      These findings are discussed relative to the use of consensus TCDD equivalency
      factors' (TEFs) for use in risk assessments of CNs for regulatory purposes.

PMID- 17454366
TI  - Utilization of the Phaseolus vulgaris L. Waste biomass for decolorization of the
      textile dye Acid Red 57: determination of equilibrium, kinetic and thermodynamic
      parameters.
AB  - In the present study, biosorption of Acid Red 57 (AR57) onto a waste biomass of
      Phaseolus vulgaris L. was investigated by varying pH, contact time, biosorbent
      concentration and temperature, to determine the equilibrium, thermodynamic and
      kinetic parameters. The AR57 biosorption was fast, and equilibrium was attained
      within 20 min. Biosorption equilibrium data fit the Langmuir isotherm model well
      with high correlation coefficients. According to Langmuir isotherm model the
      maximum biosorption capacity of Phaseolus vulgaris L. for AR57 dye was determined
      as 4.09 x 10(- 4) mol g(- 1) or 215.13 mg g(- 1) at 20 degrees C. The
      thermodynamic parameters (Gibbs free energy, enthalpy and entropy) for the
      biosorption of AR57 were indicated that the biosorption was spontaneous and
      exothermic in nature. The pseudo-second-order kinetic model agrees well with the
      dynamic behavior of the biosorption of AR57 onto P. vulgaris L., under various
      temperatures. The removal efficiency of the biomass was also examined in real
      textile wastewater.

PMID- 17454367
TI  - Qualitative monitoring of tertiary treated wastewater reuse extensive
      distribution system: total coliforms number and residual chlorine concentration.
AB  - During a 5-month summer period, samples of tertiary treated wastewater flowing in
      an extensive distribution system composed of storage tanks and pipes were
      collected at 2-week intervals, from 21 different sampling points, including the
      exit from the wastewater treatment plant (WWTP). The WWTP producing this effluent
      treated one of the most popular European tourist resorts on the north coast of
      the island of Crete, at the southernmost point of Greece. The average summer
      equivalent population treated by the plant exceeded 50,000, falling to under
      5,000 in the winter. The samples were analyzed for total coliforms number (TC in
      cfu / 100 mL) and residual chlorine concentration (RCHL in mg/L). In almost 60%
      of the samples the TC number was so large that it could be safe to suggest that
      the WWTP and distribution system failed to reach the EPA standards for wastewater
      reuse for tree irrigation (faecal coliforms < or = 200 cfu/100 mL and RCHL < 1
      mg/L) due mainly to inflow and septage handling, above designed limits. The
      licensing operational and reuse standards were set in TC < or = 500 cfu/100 mL,
      where 76% of the analyzed samples recorded larger values. It was also estimated
      that in 14% of the samples the wastewater quality failed to reach even the less
      strict WHO standards of FC < or = 1.000 cfu/100 mL. When chlorination was
      properly adjusted the effluent quality was improved (last three sets of samplings
      for each collection point), helped by the WWTP inflow decrease. As a result the
      values recorded in all tanks and collectors were also improved. However, even
      then, the required licensing standards were randomly and barely achieved. This
      suggests that specific wastewater quality standard at the exit of a WWTP do not
      guarantee that the wastewater will still retain these characteristics at its
      final application point.

PMID- 17454368
TI  - A microcalorimetric method for studying the toxic effect of different diphenol
      species on the growth of Escherichia coli.
AB  - A microcalorimetric technique based on bacterial heat-output was explored to
      evaluate the toxic effect of different diphenol species on the growth of
      Escherichia coli (E. coli). Power-time curves of the growth metabolism for E.
      coli in the presence of different diphenol species were studied using a multi
      channel microcalorimetric system with an ampoule method at 37 degrees C. The
      growth rate constant (k), generation time (t(G)), inhibitory ratio (I), half
      inhibitory concentration (IC(50)) and the total thermal effect (Q(T)) for E. coli
      were obtained. The results show that catechol and hydroquinone are more toxic to
      E. coli than resorcinol. In all cases, the growth rate constants of E. coli (in
      log phase) decreased as the concentrations of these diphenols increased. Among
      these diphenols species, catechol was found to be the most poisonous species at
      an IC(50) of 323.5 micro g/mL against E. coli. Hydroquinone exhibited moderate
      virulence with an IC(50) of 1196 micro g/mL and resorcinol had the lowest
      toxicity with an IC(50) of 2113 micro g/mL. The microcalorimetric bioassay can be
      a quantitative, inexpensive, and versatile method for acute cellular toxicity
      study.

PMID- 17454369
TI  - Kinetic and equilibrium studies on biosorption of basic blue dye by green macro
      algae Caulerpa scalpelliformis.
AB  - Dynamic batch experiments were carried out for the biosorption of basic blue dye
      on to the green macro algae Caulerpa scalpelliformis. The factors affecting the
      sorption process such as the initial concentration of the dye, pH of the
      solution, the adsorbent dosage and the time of contact were studied. It has been
      observed that the sorption process was significantly affected by the pH of the
      initial dye solution. The sorption kinetics was found to follow the second-order
      kinetic model. The Boyd's plot confirmed the external mass transfer as the rate
      limiting step. The average effective diffusion coefficient was found to be 1.652
      x 10(- 5) cm(2)/s. Sorption equilibrium studies demonstrated that the biosorption
      followed Freundlich isotherm model, which implies a heterogeneous sorption
      phenomenon. Optimized parameters were used to treat the commercial effluent
      containing the dye. Complete color removal was observed in two stages of
      treatment with the seaweed.

PMID- 17454370
TI  - Sludge reduction and volatile fatty acid recovery using microwave advanced
      oxidation process.
AB  - Sewage sludge was subjected to the combined microwave-hydrogen peroxide-sulfuric
      acid enhanced advanced oxidation process (MW-H(2)O(2)-H(+)-AOP) to evaluate the
      potential of reducing suspended solids in sludge. The soluble chemical oxygen
      demand (SCOD) and acetic acid produced were dependent on the amounts of H(2)O(2)
      and acid used in the process. For sewage sludge, a higher volume of H(2)O(2)
      addition not only favored the destruction of sludge solids, but also conserved
      the carbon content in the medium. Volatile fatty acid (VFA) concentrations also
      increased with the amount of inorganic acid in the solution. For the soluble
      fraction of solutions derived from microwave-treated sludge, over 96% of the
      total COD was in the soluble form, and up to 25% of this soluble COD was acetic
      acid. The presence of an inorganic acid was a stability factor in retaining the
      SCOD in solution, instead of the formation of carbon dioxide, resulting in
      reduced total COD in the solutions. By controlling the amounts of H(2)O(2) and
      acid addition, the MW-H(2)O(2)-H(+)-AOP could solubilize and/or reduce the sludge
      mass.

PMID- 17454371
TI  - Carbon and nitrogen removal from low-strength domestic wastewater with a two
      stage submerged biological filter.
AB  - The aim of the present study was to evaluate the secondary and tertiary treatment
      of low -strength domestic wastewater with submerged biological filters (BFs). The
      experiments were carried out with a two-stage pilot plant consisting of two
      subsequent filter columns. In the first aerated reactor, the removal of carbon
      and nitrification was accomplished (secondary nitrification); while, in the
      second anoxic reactor a post-denitrification process with methanol as external
      carbon source was performed. During the 3 months of experimental period, in
      average terms, Total Suspended Solids (TSS) concentrations of 156 mg/L were
      reduced to 5 mg/L; Chemical Oxygen Demand (COD) concentrations of 179 mg/L were
      reduced to 43 mg/L. In the secondary nitrification, mean influent NH(4)(+)
      concentrations of 6.1 mg/L were reduced to average values of 1.8 mg/L. During the
      post-denitrification, mean influent NO(3)(-) concentrations of 12.0 mg/L were
      reduced to average values of 6.1 mg/L. The overall process produced a backwashing
      effluent with an average concentration of about 175 mg/L of TSS.

PMID- 17454372
TI  - Speciation of heavy metals in untreated domestic wastewater sludge by time saving
      BCR sequential extraction method.
AB  - In this work the modified three-stage sequential extraction procedure developed
      within the Standards, Measurement and Testing Programme (formally the Community
      Bureau of Reference BCR) of the European Commission, was applied for the
      fractionation of Cd, Cr, Cu, Ni, Pb and Zn in the untreated domestic wastewater
      sludge (DWS) collected from the Hyderabad city of Pakistan. The aim of our study
      was to evaluate the impact of different time intervals for shaking, and sample
      mass of sewage sludge on optimal recovery of all metals under study. Analyses of
      the extracts were performed by flame atomic absorption spectrometry (FAAS) and
      electrothermal atomic absorption spectrometry (ETAAS). The precision and accuracy
      of the proposed procedure was evaluated by using a certified reference material
      of soil amended with sewage sludge BCR 483. The maximum recoveries for Cd and Zn
      were observed for all three steps of BCR protocol at 26 hours (h) total shaking
      period, while Cr, Cu, Ni and Pb were achieved at 32 hours instead of previously
      reported 51 hours, with (p < 0.05). The maximum level of all heavy metals was
      achieved in samples mass 0.2-0.4 g, where as the extractant-sample mass ratio was
      kept according to the optimized BCR method. The results of the sequential
      extraction study of untreated DWS indicates that more easily mobilized forms
      (acid exchangeable) were found to be 31.0, 3.1, 2.5, 7.6, 2.6 and 8.4% of total
      contents of Cd, Cr, Cu, Ni, Pb and Zn, respectively. The oxidizable fraction is
      dominant for all the heavy metals, except Cd. The lixiviation tests (DIN 38414
      S4) were used to evaluate the leaching of heavy metals from sewage sludge used
      for agricultural purposes.

PMID- 17454373
TI  - An evaluation of the performance of the soil temperature simulation algorithms
      used in the PRZM model.
AB  - Soil temperature simulation is an important component in environmental modeling
      since it is involved in several aspects of pollutant transport and fate. This
      paper deals with the performance of the soil temperature simulation algorithms of
      the well-known environmental model PRZM. Model results are compared and evaluated
      based on the basis of its ability to predict in situ measured soil temperature
      profiles in an experimental plot during a 3-year monitoring study. The evaluation
      of the performance is based on linear regression statistics and typical model
      statistical errors such as the root mean square error (RMSE) and the normalized
      objective function (NOF). Results show that the model required minimal
      calibration to match the observed response of the system. Values of the
      determination coefficient R(2) were found to be in all cases around the value of
      0.98 indicating a very good agreement between measured and simulated data. Values
      of the RMSE were found to be in the range of 1.2 to 1.4 degrees C, 1.1 to 1.4
      degrees C, 0.9 to 1.1 degrees C, and 0.8 to 1.1 degrees C, for the examined 2, 5,
      10 and 20 cm soil depths, respectively. Sensitivity analyses were also performed
      to investigate the influence of various factors involved in the energy balance
      equation at the ground surface on the soil temperature profiles. The results
      showed that the model was able to represent important processes affecting the
      soil temperature regime such as the combined effect of the heat transfer by
      convection between the ground surface and the atmosphere and the latent heat flux
      due to soil water evaporation.

PMID- 17454374
TI  - Lead-induced alterations in rat kidneys and testes in vivo.
AB  - The purpose of this study was to assess the effects of lead administration on the
      kidney and testicular structure of adult rats. Rats received lead (PbNO(3)) in
      single intraperitoneal dose 50 mg/kg (group A), 25 mg/kg (group B) and 12.5 mg
      (group C) per kilogram of body weight and were killed 48 h following lead
      administration. After the preparation of histological samples the results were
      compared with control. After the lead administration dilated Bowman's capsules
      and blood vessels in interstitium of kidney with evident hemorrhagic alterations
      were noted. Quantitative analysis determined increased relative volume of
      interstitium and tubules. Also, the diameter of renal corpuscules, diameter of
      glomeruli and diameter of Bowman's capsule were significantly increased,
      especially in group A, with the highest lead concentration. In testes, dilatation
      of blood capillaries in interstitium, undulation of basal membrane and occurrence
      of empty spaces in seminiferous epithelium were detected. An apoptosis assay
      confirmed increased incidence of apoptosis in the spermatogenetic cells after the
      lead administration. Also further morphometric analysis showed significant
      differences in evaluated parameters between control and treated groups. The
      number of cell nuclei was decreased in lead-treated groups, which is concerned
      with the occurrence of empty spaces as well as with the higher apoptosis
      incidence in germinal epithelium. This study reports a negative effect of lead on
      the structure and function of kidney and testes.

PMID- 17454375
TI  - Preparation and ecotoxicity assessment of new biodegradable polyurethane foams.
AB  - Flexible biodegradable polyurethane foams (BIO-PUR) were prepared by a one-shot
      process using commercially available coreactants and modified by substituting
      biodegradable additive based on the acetylated starch (AS), acetylcellulose (AC),
      2-hydroxyethylcellulose (HEC) and carboxymethylcellulose sodium salt (CMC) for 5
      or 10 wt% of commercial polyether polyol. The BIO-PUR foams were characterized by
      FTIR, TGA and polarization microscopy. Ecotoxicity of BIO-PUR foams freshwater
      extracts was evaluated using the alternative crustacean toxicity test
      Thamnotoxkit F. Values of toxicity were expressed as percentage mortality of the
      instars II-III larvae of freshwater fairy shrimps (Thamnocephalus platyurus)
      dependence on the effect criterion of the respective assay. The leaches of BIO
      PUR foams modified with 5 or 10 wt% of HEC showed higher toxicity then other BIO
      PUR foams, whereas leaches of BIO-PUR with 5wt% of AS and 10wt% of AC were even
      less toxic than REF. PUR foam.

PMID- 17454376
TI  - Behavior of bensulfuron-methyl in an agricultural alkaline soil.
AB  - A field experiment to determine the available bensulfuron-methyl (BSM) in the
      upper soil layer was conducted in an agricultural area in the South of Spain. To
      facilitate herbicide analysis, two application rates were employed, 200 g ha(-1)
      and 5 kg ha(-1). Samples of upper soil and soil solution were collected. Soil
      solution was sampled by means of metallic samplers, placed at a depth of 35 cm.
      In the plots receiving the lower dose ceramic suction, porous cups were also
      installed. Results from soil solution samples showed that the maximum BSM
      concentration was found after 8-10 days for the high irrigation supply (945 mm)
      and after 18-25 days for the lower irrigation regime (405 mm). The mathematical
      model FOCUSPELMO 1.1.1 was applied to interpret the data obtained in the field
      experiments. In general, there was a reasonable agreement between experimental
      and simulated data for soil samples, although the model did not acceptably
      predict herbicide concentrations in water soil samples. Ceramic cups sampled a
      higher soil water volume and more frequently than did the metallic samplers.
      However some variable results were attributed to preferential flow.

PMID- 17454377
TI  - Combined effect of diuron and simazine on photosystem II photochemistry in a
      sandy soil and soil amended with solid olive-mill waste.
AB  - Diuron (3-(3,4-dichlorophenyl)- = 1,1-dimethylurea) and simazine (6-chloro-N(2),
      N(4)-diethyl-1,3,5-triazine-2,4-diamine) are soil-applied herbicides used in
      olive crops. The objective of this study is to investigate the effect of these
      herbicides on Photosystem II photochemistry of Olea europaea L., and whether the
      amendment of soil with an organic waste (OW) from olive oil production industry
      modifies this effect. For this purpose, herbicide soil adsorption studies, with
      unamended and OW-amended soil, and chlorophyll fluorescence measurements in adult
      olive leaves, after one, two and three weeks of soil herbicide treatment and/or
      OW amendment, were performed. Soil application of these herbicides reduced the
      efficiency of Photosystem II photochemistry of olive trees due to chronic
      photoinhibition, and this effect is counterbalanced by the addition of OW to the
      soil. OW reduces herbicide uptake by the plant due to an increase in herbicide
      adsorption.

PMID- 17454378
TI  - 2,4-D Mineralization in soil profiles of a cultivated hummocky landscape in
      Manitoba, Canada.
AB  - The objective of this study was to quantify 2,4-D (2,4-dichlorophenoxyacetic
      acid) mineralization in soil profiles characteristic of hummocky, calcareous-soil
      landscapes in western Canada. Twenty-five soil cores (8 cm inner diameter, 50 to
      125 cm length) were collected along a 360 m transect running west to east in an
      agricultural field and then segmented by soil-landscape position (upper slopes,
      mid slopes, lower slopes and depressions) and soil horizon (A, B, and C
      horizons). In the A horizon, 2,4-D mineralization commenced instantaneously and
      the mineralization rate followed first-order kinetics. In both the B and C
      horizons, 2,4-D mineralization only commenced after a lag period of typically 5
      to 7 days and the mineralization rate was biphasic. In the A horizon, 2,4-D
      mineralization parameters including the first-order mineralization rate constant
      (k(1)), the growth-linked mineralization rate constant (k(2)) and total 2,4-D
      mineralization at the end of the experiment at 56 days, were most strongly
      correlated to parameters describing 2,4-D sorption by soil, but were also
      adequately correlated to soil organic carbon content, soil pH, and carbonate
      content. In both B and C horizons, there was no significant correlation between
      2,4-D mineralization and 2,4-D sorption parameters, and the correlation between
      soil properties and 2,4-D mineralization parameters was very poor. The k(1)
      significantly decreased in sequence of A horizon (0.113% day(-1)) > B horizon
      (0.024% day(-1)) = C horizon (0.026% day(-1)) and in each soil horizon was
      greater than k(2). Total 2,4-D mineralization at 56 days also significantly
      decreased in sequence of A horizon (42%) > B horizon (31%) = C horizon (27%). In
      the A horizon, slope position had little influence on k(1) or k(2), except that
      k(1) was significantly greater in upper slopes (0.170% day(-1)) than in lower
      slopes (0.080% day(-1)). Neither k(1) nor k(2) was significantly influenced by
      slope position in the B or C horizons. Total 2,4-D mineralization at 56 days was
      not influenced by slope positions in any horizon. Our results suggest that, when
      predicting 2,4-D transport at the field scale, pesticide fate models should
      consider the strong differences in 2,4-D mineralization between surface and
      subsurface horizons. This suggests that 2,4-D mineralization is best predicted
      using a model that has the ability to describe a range of non-linear
      mineralization curves. We also conclude that the horizontal variations in 2,4-D
      mineralization at the field scale will be difficult to consider in predictions of
      2,4-D transport at the field scale because, within each horizon, 2,4-D
      mineralization was highly variable across the twenty-five soil cores, and this
      variability was poorly correlated to soil properties or soil-landscape position.

PMID- 17454379
TI  - Influence of crop residues on trifluralin mineralization in a silty clay loam
      soil.
AB  - Trifluralin is typically applied onto crop residues (trash, stubble) at the soil
      surface, or onto the bare soil surface after the incorporation of crop residues
      into the soil. The objective of this study was to quantify the effect of the type
      and amount of crop residues in soil on trifluralin mineralization in a Wellwood
      silty clay loam soil. Leaves and stubble of Potato (Solanum tuberosum) (P);
      Canola (Brassica napus) (C), Wheat (Triticum aestivum) (W), Oats (Avena sativa),
      (O), and Alfalfa (Medicago sativa) (A) were added to soil microcosms at rates of
      2%, 4%, 8% and 16% of the total soil weight (25 g). The type and amount of crop
      residues in soil had little influence on the trifluralin first-order
      mineralization rate constant, which ranged from 3.57E-03 day(-1) in soil with 16%
      A to 2.89E-02 day(-1) in soil with 8% W. The cumulative trifluralin
      mineralization at 113 days ranged from 1.15% in soil with 16% P to 3.21% in soil
      with 4% C, again demonstrating that the observed differences across the
      treatments are not of agronomic or environmental importance.

PMID- 17454380
TI  - 3D-QSAR of fungal quorum-sensing inhibiting analogs of farnesol.
AB  - Thirty-four analogs with variable antifungal activity were selected to develop
      models for establishing three-dimensional quantitative structure-activity
      relationships (3D-QSAR). Comparative molecular field analysis (CoMFA) and
      comparative similarity indices analyses (CoMSIA) were conducted on the group of
      analogs to determine the structural requirements for selectivity and potency in
      inhibiting biofilm formation and fungal growth. The best CoMFA model predicted a
      q(2) = 0.5 and an r(2) = 0.991, and revealed that electrostatic properties play a
      significant role in potency and selectivity. The best CoMSIA model combined
      electrostatics, hydrogen bond acceptor and donor, and hydrophobic fields with a
      q(2) = 0.664 r(2) = 0.952, S = 0.099, and F = 139.892. The analyses of the
      contour maps from both models provide significant insight into the structural
      necessities for a potent compound. Therefore, manipulating various chemical
      properties of the substituted groups on the farnesol chain can be used to enhance
      the fungicidal properties of the target compound.

PMID- 17454381
TI  - Ecological effects of imidacloprid on arthropod communities in and around a
      vegetable crop.
AB  - To elucidate the ecological impacts of imidacloprid [1-(6-chloro-3-pyridylmethyl)
      N-nitroimidazolidin-2-ylideneamine] on vegetable crops and their surrounding
      areas, arthropods on eggplant patches treated with this insecticide were
      monitored throughout two cultivation seasons, spring and autumn, and the results
      compared with those of control crops. Residues of imidacloprid in soil accounted
      for 4-8% of total applied, and concentrations outside the crop were always below
      5 micro g/kg. Communities of the crop vegetation experienced significant density
      reductions, mostly of aphids, and had fewer species diversity during the first
      month. Those in the surrounding pasture were similarly affected though with less
      intensity, while non-target ground arthropods both inside and outside the crop
      only showed significant impacts in the two weeks after planting.

PMID- 17454382
TI  - Impact of pH buffer capacity of sediment on dechlorination of atrazine using zero
      valent iron.
AB  - This research investigated the role of the pH buffer capacity of sediment on the
      dechlorination of atrazine using zero valent iron (ZVI). The buffer capacity of
      the sediment was quantified by batch experiments and estimated to be 5.0 cmol OH(
      ) . pH(-1). The sediments were spiked with atrazine at 7.25-36.23 mg kg(-1) (6.21
      x 10(-7)-3.09 x 10(-6) mol atrazine . g(-1) sediment) for the batch experiments.
      The buffer capacity of the sediment maintained the sediment suspension at neutral
      pH, thereby enabling continuous dechlorination until the buffer capacity of the
      sediment was depleted. The pseudo-first order dechlorination constants were
      estimated to be in the range of 1.19 x 10(-2)-7.04 x 10(-2) d(-1) for the
      atrazine-spiked sediments.

PMID- 17454383
TI  - Acetylcholinesterase-polyaniline biosensor investigation of organophosphate
      pesticides in selected organic solvents.
AB  - The behavior of an amperometric organic-phase biosensor consisting of a gold
      electrode modified first with a mercaptobenzothiazole self-assembled monolayer,
      followed by electropolymerization of polyaniline in which acetylcholinesterase as
      enzyme was immobilized, has been developed and evaluated for organophosphorous
      pesticide detection. The voltammetric results have shown that the formal
      potential shifts anodically as the Au/MBT/PANI/AChE/PVAc thick-film biosensor
      responded to acetylthiocholine substrate addition under anaerobic conditions in
      selected organic solvent media containing 2% v/v 0.05 M phosphate buffer, 0.1 M
      KCl (pH 7.2) solution. Detection limits in the order of 0.147 ppb for diazinon
      and 0.172 ppb for fenthion in acetone-saline phosphate buffer solution, and 0.180
      ppb for diazinon and 0.194 ppb for fenthion in ethanol-saline phosphate buffer
      solution has been achieved.

PMID- 17454384
TI  - Surfactant effect on persistence of oxadiazolyl 3(2H)-pyridazinones against
      Pseudaletia separata walker.
AB  - The photodynamic decomposition of two new insect-growth inhibitors (IGRs), 2-tert
      butyl-5-[5'-aryl-2'-(1',3',4'-oxadiazolyl)methoxy]-3(2H)-pyridazinones (OPB) and
      its 4-chloro substituted derivative (OPC), and effect of surfactants on
      persistence of their bioactivity were taken into investigation. Both chemicals
      were significantly induced to photolysis by ultraviolet light at 365 nm
      wavelength and their inhibitory activities against Pseudaletia separata larvae
      decreased with the increasing irradiation time. However, irradiation at 254 nm
      wavelength didn't cause their photodegradation. Triton X-100 and Succinic
      sulfonie acidic sodium but not Tween 60 possessed strong capability to slow down
      the decomposition and obviously prolonged the half life of OPC in laboratory and
      field whilst effects of the three surfactants almost did not preserve the
      inhibitory activity of OPB. Data suggested that electron-withdrawing halogen (
      Cl) on the pi electron system in planar benzene-oxadialyl structures might reduce
      the efficiency of OPC on ultraviolet (UV) photoabsorption, and its hydrophobic
      interaction with the surfactants might be beneficial for forming stable micellar
      solubilization, thus sustaining the chemical's bioactivity.

PMID- 17454385
TI  - Organochlorine pesticides and polychlorinated biphenyls in surface soils of Novi
      Sad and bank sediment of the Danube River.
AB  - The contents of 16 organochlorine pesticides (OCPs) and six so-called indicator
      polychlorinated biphenyls (PCBs) were determined in the surface zone (0-5 cm) of
      soil and sediment samples, taken from different locations in the city of Novi
      Sad, capitol of Vojvodina Province (North of the Serbia) covering residential and
      commercial area, recreational and arable zone. The total organochlorine
      pesticides concentration in soil varied from 2.63 to 31.78 ng g(-1) dry weight,
      while the level in sediment was 10.35 ng g(-1) dry weight. Maximum content of
      identified individual organochlorine pesticide in soil samples was 10.40 ng g(-1)
      dry weight for p, p-DDE in the market garden and 6.31 ng g(-1) dry weight for p,
      p'-DDT in sediment of the Danube River, although their application is restricted
      in Serbia. Some of investigated PCBs were identified only in the soil samples
      from a park-school backyard in the city downtown (0.32 ng g(-1) dry weight) and
      market garden (0.22 ng g(-1) dry weight), and also in sediment sample from left
      bank of the Danube River (0.41 ng g(-1) dry weight). Data of the OCPs and PCBs
      present in this study were compared with the ones found for soils and river
      sediments throughout the world, and with limit values set by soil and sediment
      quality guidelines. Also, correlation between the levels of certain pesticides
      and soil characteristics (organic matter, pH and clay content) was investigated.

PMID- 17454386
TI  - Degradation of indulin, a kraft pine lignin, by Serratia marcescens.
AB  - Serratia marcescens isolated from decaying coconut pith exhibited high lignolytic
      activity. Growth on indicator medium, analysis of residual indulin, and infra-red
      spectroscopic analysis indicated the lignolytic potential of the isolate. Ortho
      Coumaric acid, ferulic acid, 2,3-dihydroxy cinnamic acid and protocatechuic acid
      were identified as intermediates involved in indulin degradation by S.
      marcescens. Qualitative confirmation and quantitative estimation of the
      intermediates were carried out by high performance thin layer chromatography
      (HPTLC).

PMID- 17454387
TI  - Bendiocarbamate induced structural alterations in rabbit thymus after
      experimental peroral administration.
AB  - In this study histological structure of rabbit thymus after bendiocarbamate (2,3
      isopropyledene-dioxyphenyl methylcarbamate) administration was studied.
      Bendiocarbamate was perorally administered for 90 days. At Day 3, 10, 20, 30, 60,
      90 morphometric analysis was realized. Quantitative evaluation showed that in the
      control group thymus cortex forms 57.94 +/- 7.10% and medulla 35.94+/- 7.38%. In
      almost all experimental groups significantly higher relative volume of cortex and
      lower relative volume of medulla was detected. Detail morphometric analysis found
      that the number of thymocytes per constant area and the diameter of tymocytes was
      decresed after bendiocarbamate administration. The number and diameter of
      reticular cells was not affected. Results of this study suggest negative effect
      of bendiocarbamate on the formation of thymus structures.

PMID- 17454388
TI  - Accumulation of polonium 210Po in tissues and organs of deer carvidae from
      Northern Poland.
AB  - This study was undertaken to provide information on accumulation of polonium in
      tissues and organs of deer carvidae in order to assess the potential transport of
      this element via food-chain to game meat consumers. Livers, kidneys and muscles
      of large herbivorous animals belonging to three species: roe deer (Capreolus
      capreolus), red deer (Cervus elaphus) and fallow deer (Dama dama), collected in
      Northern Poland, were the subject of the present investigation. Activities of
      (210)Po were determined by means of alpha spectrometry along with relevant
      radiochemical procedures. The concentration of (210)Po in analyzed animals
      decreased in the order kidney > liver > muscle tissue. The average activity
      concentrations of (210)Po ranged between 0.02 +/- 0.01 Bq. kg(- 1) w.w. in
      muscles and 7.15 +/- 0.12 Bq. kg(- 1) w.w. in kidneys. Levels of polonium were
      not influenced by sampling location, sex, age and species of animals.

PMID- 17454390
TI  - Humility.
AB  - Humility is a virtue worth considering in the daily activities of the surgeon's
      practice. How can we teach humility to future generations of surgeons and bring
      about its recognition within their professional duties? That is not a simple task
      but needs to be addressed. A fictional example illustrates a situation in which
      humility might be an appropriate response. Humility, it has been said, "is the
      foundation of the spiritual edifice" [1]. Blaise Pascal stated, "Do you wish
      people to think well of you? Don't speak well of yourself." All these
      characteristics of human behavior need to be incorporated into the education of
      the surgical professional. In closing, be humble and patients and colleagues will
      discover the strength of your character.

PMID- 17454391
TI  - Something the Lord Made.
AB  - When Alfred Blalock (1899-1965), the pioneer Hopkins surgical professor, saw the
      pulmonary artery suturing technique that his laboratory technician, Vivien Thomas
      (1910-1985), had just performed in a dog, his level of astonishment was so high
      that he expressed, "Vivien, this looks like Something the Lord Made." In all his
      years of practice, Dr. Blalock had never seen anything like it before. The level
      of perfection was so superior to other works that it could not be considered to
      be of human descent. The surgical technician far exceeded anyone else in the
      surgical department. In due time, he taught surgical residents and faculty the
      exquisite details of the laborious vascular suturing techniques. Thomas and
      Blalock learned to respect and appreciate each other's work. Thomas, the advanced
      student, and Blalock, the noted teacher, learned to understand one another and
      recognize their unique abilities. With the support and theoretical advice of his
      mentor, Thomas proceeded in the old Hunterian Laboratory to solve the problem of
      the Blue Baby heart disease, also known as Tetralogy of Fallot. The fruits of
      Thomas's work were put to a test on November 29, 1944, when surgeon-in-chief
      Blalock took baby Eileen to room 706 to perform the first pulmonary artery to
      subclavian artery shunt in humans. The results were especially good, and baby
      Eileen recovered satisfactorily. It was obvious that history had been made, and
      Thomas and Blalock were the creators, the heroes of this extraordinary feat. They
      had participated together in Something the Lord Made.

PMID- 17454392
TI  - Selectin inhibitors and their proposed role in ischemia and reperfusion.
AB  - The selectin family of cellular adhesion molecules plays an important role in the
      cellular infiltration and molecular signaling associated with
      ischemia/reperfusion (I/R). Selectins are essential in the recruitment and
      infiltration of leukocytes to sites of inflammation, and consequently, selectin
      blockade represents an important area of current research in the potential
      alleviation of the cell-mediated injury associated with I/R. Previously,
      treatments targeted at only a single selectin have proven ineffective, due to
      compensation by uninhibited cell-adhesion molecules. However, pan-selectin
      antagonists - those inhibitors capable of blocking the actions of all three
      selectins - have demonstrated great potential in blocking the initial events in
      the leukocyte-endothelium adhesion cascade. A number of therapeutics have been
      developed, with the most promising results demonstrated by a class of non
      oligosaccharide, small-molecule selectin antagonists. TB-1269 and OC-229 are two
      of the most promising of inhibitors in this class - they are capable of binding
      all three selectins, they have been demonstrated to reduce neutrophil
      infiltration following ischemia/reperfusion, and they have been associated with
      reduced tissue damage in experimental animal models of ischemia/reperfusion
      involving the liver, the heart, the kidneys, and the whole body. Furthermore, TBC
      1269 has recently undergone successful phase I and phase IIa clinical trials for
      asthma and psoriasis. Though the timing of selectin inhibition is essential in
      attenuating leukocyte infiltration and cell-mediated injury, the transient
      blockade of selectin function, in a well-controlled setting, could be an
      extremely beneficial intervention in ischemia/reperfusion injury.

PMID- 17454393
TI  - Rodent models for the study of articular fracture healing.
AB  - The goal of this study was to document the healing time course and expression of
      ex vivo cell-based gene delivery in articular fracture models in the mouse and
      rat. Articular medial intercondylar femoral osteotomy was performed in the stifle
      (knee) joints of hairless immunocompetent mice and medial or lateral similar
      osteotomy was performed in athymic nude rats. Genetically modified cells
      expressing luciferase were delivered in a three-dimensional alginate matrix
      directly into the osteotomy site. Sensitivity of an in vivo imaging system to
      detect expression of luciferase was compared between rodents in this fracture
      model. Osteotomy healing was assessed using high-detail radiography, helical
      computed tomography (CT), high-field magnetic resonance imaging, and histology.
      The mouse model was less satisfactory because the small size of the murine femur
      made reliable assessment of fracture healing restricted to histopathology, and
      complications occurred in 11/24 mice (45.8%), most frequently transverse
      supracondylar femoral fracture postoperatively. Gene expression was
      inconsistently confirmed in mice in vivo for 11 days (p < .003). In rats, high
      detail radiography and CT were used to assess osteotomy healing. Magnetic
      resonance imaging (4.7 T) in rats could produce three-dimensional images that
      would permit assessment of bone and cartilage, but was time-consuming and
      expensive. In rats, the only surgical complication, transverse femoral fracture,
      was reduced from 83.3% with the medial osteotomy to 0% with a lateral osteotomy.
      In vivo imaging confirmed gene expression in the alginate/cell constructs in rats
      for at least 4 days (p < .05). The nude rat model has the advantage of larger
      femora and the ability to implant xenograft cells. A lateral intercondylar
      osteotomy of the distal femur in the rat can be used to study the healing of
      articular fractures.

PMID- 17454394
TI  - Effect of caspase inhibition on thymic apoptosis in hemorrhagic shock.
AB  - In hemorrhagic shock (HS) an increased thymic apoptosis (TA) was described. The
      aim of this study was to evaluate the effect of administration of the caspase
      inhibitor N-benzyloxy-carbonil-Val-Ala-Asp-fluoromethylketone (Z-VAD-FMK) during
      the resuscitation phase on TA, organ dysfunctions, and tumor necrosis factor
      (TNF)-alpha release in HS. Forty rats were randomly assigned to four groups: no
      HS/resuscitation (sham); HS/resuscitation with shed blood and normal saline
      (control); HS/resuscitation with shed blood and phosphate-buffered solution (PBS)
      (vehicle); and HS/resuscitation with shed blood and Z-VAD-FMK (inhibitor). Rats
      were subjected to HS by blood removal to a MAP of 35-40 mmHg. After a 1-h shock
      period, the animals were resuscitated according to the protocol. At 1 and 3 h
      after resuscitation, transaminases, creatinine, urea, lipase, TNF-alpha, and TA
      were evaluated. Our study showed that a nonlethal HS is early able to induce
      organ dysfunctions and increased TA. Administration of Z-VAD-FMK did not
      significantly decrease organ dysfunctions, while it induced a significant TNF
      alpha release. TA was significantly reduced by Z-VAD-FMK after 1 h, but not after
      3 h. Our results suggest that postinjury caspase inhibition does not attenuate
      organ dysfunctions, and also does not permanently reduce TA induced by HS and
      resuscitation in rats.

PMID- 17454395
TI  - The comparison of mitogen-activated protein kinases that become activated within
      the left ventricular and right atrial tissues following heart transplantation in
      canine model.
AB  - The activation of p38 mitogen-activated protein kinase (MAPK) plays an important
      role in ischemia/reperfusion injury. Some reports have documented MAPKs
      activation of the myocardium in human models, using right atrial (RA) tissue for
      samples. This study compared the activation of MAPKs in left ventricle (LV) and
      RA tissues in canine heart transplantation. Four dogs were used as baseline data
      at two points, before and 20 min after warm ischemia (baseline model), and eight
      dogs (four pairs of donor and recipient) were used at other points: 4 h after
      cold ischemia, and at 10, 60, and 180 min after reperfusion (transplantation
      model). In the transplantation model, donor hearts were left in situ for 20 min
      after cardiac arrest, and were immersed in Celsior solution for 4 h after
      coronary flushing. Orthotopic heart transplantation was then performed. Two
      groups were created: the LV and RA groups (n = 4 in each group). Heart tissue was
      harvested from the left ventricular wall in the LV group and from the right
      atrial appendage in the RA group. The activation of MAPKs, including p38 MAPK, c
      Jun N-terminal protein kinase (JNK), and extracellular signal-regulated protein
      kinase (ERK), was evaluated at each point. The activation patterns of p38 MAPK
      and ERK were similar in the RA and LV groups, but JNK activation was different in
      the two groups, after ischemia and reperfusion. Thus, RA tissue may be
      deliberately used as a substitute for LV tissue when investigating the activation
      of MAPKs in a human model.

PMID- 17454396
TI  - Cyclosporin A has a protective effect with induced upregulation of Hsp70 and nNOS
      on severe spinal cord ischemic injury in rabbits.
AB  - The purpose of this study is to ascertain the neuroprotective effect of
      cyclosporin A on the 25-min surgical ischemia model in the spinal cords of
      rabbits with neuropathological correlation and histoimmunochemical analyses
      measuring HSP70 and neuronal NOS (nNOS). New Zealand white rabbits were randomly
      divided into four groups (each n = 8): the C2, C7, Cs2, and Cs7 groups. The C2
      and C7 groups underwent a 25-min surgical aortic cross-clamp without intervention
      and were sacrificed respectively on day 2 and on day 7 postoperatively. The Cs2
      and Cs7 groups received cyclosporin A (25 mg/kg) intravenously 15 min after the
      25-min cross-clamp and were sacrificed respectively on day 2 and day 7
      postoperatively. Neurologic functions were evaluated on postoperative days 2 and
      7 using the Tarlov scoring system. Then the rabbits were sacrificed for
      histopathologic observation. HSP 70 and nNOS stains with TUNEL assay were done
      for the C2 and Cs2 groups. All rabbits survived the experimental procedure.
      Tarlov's score for the Cs7 group (2.75 +/- 0.89) was significantly higher than
      that of the C7 group (1.25 +/- 1.39) (p < .05). Tarlov's score of the Cs7 group
      was also statistically higher on day 7 than on day 2 (p < .05). Strong
      correlation between the neurological and histological scorings was found. The
      TUNEL assay showed that the mean number of positive cells in the C2 group was
      17.5 +/- 22.6 and in the Cs2 group was 12.5 +/- 11.1, but there was no
      statistically significant difference between the groups. There was more
      expression of HSP70 and nNOS in the cyclosporin groups than in the ischemia
      groups. In conclusion, this study demonstrates that cyclosporin A reduces
      neurological injury in the rabbit model of 25-min spinal cord ischemia. The
      neuroprotective effect of cyclosporin A against ischemia seems to be related to
      overexpressions of nNOS and HSP70.

PMID- 17454397
TI  - Newly developed hybrid suture without lubricant: noninvasive in vivo assessment
      of biocompatibility with multiparametric MR imaging.
AB  - Magnetic resonance imaging (MRI) and magnetic resonance (MR) relaxometry were
      used to assess noninvasively the tissue response of a new uncoated hybrid braided
      suture made from a combination of ultra-high-molecular-weight polyethylene
      (UHMWPE) and polyester (polyethylene terephthalate) (PET) yarns in comparison to
      a silicone impregnated braided 100% polyester (PET) control suture (Ticron). Both
      biomaterials were monitored for a period of 30 days following implantation in
      both incised and nonincised paravertebral rabbit muscles. In all cases, MR images
      and relaxometry demonstrated that the hybrid suture elicited either a milder or a
      similar tissue and cellular response compared to the control suture. These
      findings were confirmed by conventional histological analysis of the surrounding
      tissues. They also demonstrated that the hybrid suture promoted faster healing in
      terms of collagen infiltration between the yarns and individual filaments. This
      milder inflammatory reaction and improved biocompatibility represent a real
      advantage in the healing performance of sutures for cardiac and vascular surgery,
      and support the need for continued research and development of hybrid structures.
      This study also demonstrated the ability of MRI techniques to noninvasively
      evaluate the biocompatibility of biomaterials. By extending the capacity of MR
      diagnostic tools from patients to experimental animals, it is now possible to
      validate the healing performance of foreign materials with statistical
      reliability and fewer animals.

PMID- 17454398
TI  - End-to-side portacaval shunt: a simplified technique.
AB  - A simplified technique of end-to-side portacaval shunt in the rat is described,
      consisting in using a microsuture with a looped end. By using this technique,
      combined with two-step portal vein venotomy, the portal vein and caval vein can
      be brought closer together in a single movement, with no need for a knot at the
      start of the shunt. As a result, this modified technique makes it easier and
      reduces the time required to perform the shunt, without any rise in associated
      mortality.

PMID- 17454399
TI  - Antinucleosome antibody-modified liposomes and lipid-core micelles for tumor
      targeted delivery of therapeutic and diagnostic agents.
AB  - Liposomes and lipid-core micelles prepared of polyethylene glycol
      phosphatidylethanolamine (PEG-PE) conjugates have been modified with nucleosome
      specific monoclonal antinuclear autoantibody (ANA) 2C5 (mAb 2C5) specifically
      recognizing a broad variety of cancer cells through the cancer cell surface-bound
      nucleosomes. mAb 2C5 preserves its specific properties upon the binding with the
      lipid-based pharmaceutical nanocarriers, and 2C5-modified immunoliposomes and
      immunomicelles demonstrate an enhanced binding with tumor cells both in vitro and
      in vivo. We have investigated the delivery of therapeutic and diagnostic agents
      with such tumor-targeted immunoliposomes and immunomicelles to various tumors in
      vivo and in vitro. Both lipid-based nanocarriers provided enhanced tumor delivery
      of imaging agents ((111)In) and antitumor drugs (doxorubicin and photodynamic
      therapy agents) to tumor cells under different experimental settings.
      Pharmaceutical lipid-based nanoparticular carriers modified with mAb 2C5 could
      represent universal systems for tumor-specific delivery of various soluble and
      insoluble pharmaceuticals.

PMID- 17454400
TI  - Vesicular phospholipid gels: a technology platform.
AB  - Vesicular phospholipid gels (VPGs) represent semi-solid phospholipid dispersions.
      Their morphology is truly vesicular with aqueous compartments both within the
      core of the vesicles and in-between the vesicles. VPGs are suited to carry both
      hydrophilic, amphiphilic and lipophilic drugs. Their drug load is stable since
      there is no concentration gradient between the vesicles' core and the surrounding
      water phase. VPGs are suited to release drugs in a controlled manner, and thus
      may serve as depot implants. When blended with excess aqueous medium VPGs are
      easily converted into small-sized liposome (SUV) dispersions showing high
      encapsulation efficiencies for all kinds of drugs. VPG-formulations with various
      cytostatic drugs have been tested successfully in human xenografts. Obviously,
      the vesicles protect the drugs from premature metabolic inactivation and/or
      elimination and guide them to solid tumors with enhanced vascular permeability
      (passive targeting). Furthermore, when mounted on a filter support, VPGs
      represent a tight diffusion barrier suitable for screening of oral drug
      permeability, as demonstrated by a set of 21 drug compounds. Permeability values
      were shown to fit well with human absorption in vivo, indicating that the model
      is suited for rapid screening of passive transport properties of new chemical
      entities.

PMID- 17454401
TI  - Environmental scanning electron microscopy offers real-time morphological
      analysis of liposomes and niosomes.
AB  - Liposomes have been imaged using a plethora of techniques. However, few of these
      methods offer the ability to study these systems in their natural hydrated state
      without the requirement of drying, staining, and fixation of the vesicles.
      However, the ability to image a liposome in its hydrated state is the ideal
      scenario for visualization of these dynamic lipid structures and environmental
      scanning electron microscopy (ESEM), with its ability to image wet systems
      without prior sample preparation, offers potential advantages to the above
      methods. In our studies, we have used ESEM to not only investigate the morphology
      of liposomes and niosomes but also to dynamically follow the changes in structure
      of lipid films and liposome suspensions as water condenses on to or evaporates
      from the sample. In particular, changes in liposome morphology were studied using
      ESEM in real time to investigate the resistance of liposomes to coalescence
      during dehydration thereby providing an alternative assay of liposome formulation
      and stability. Based on this protocol, we have also studied niosome-based systems
      and cationic liposome/DNA complexes.

PMID- 17454402
TI  - Cellular delivery of siRNA mediated by fusion-active virosomes.
AB  - RNA interference is expected to have considerable potential for the development
      of novel specific therapeutic strategies. However, successful application of RNA
      interference in vivo will depend on the availability of efficient delivery
      systems for the introduction of small-interfering RNA (siRNA) into the
      appropriate target cells. This paper focuses on the use of reconstituted viral
      envelopes ("virosomes"), derived from influenza virus, as a carrier system for
      cellular delivery of siRNA. Complexed to cationic lipid, siRNA molecules could be
      efficiently encapsulated in influenza virosomes. Delivery to cultured cells was
      assessed on the basis of flow cytometry analysis using fluorescently labeled
      siRNA. Virosome-encapsulated siRNA directed against Green Fluorescent Protein
      (GFP) inhibited GFP fluorescence in cells transfected with a plasmid encoding GFP
      or in cells constitutively expressing GFP. Delivery of siRNA was dependent on the
      low-pH-induced membrane fusion activity of the virosomal hemagglutinin,
      supporting the notion that virosomes introduce their encapsulated siRNA into the
      cell cytosol through fusion of the virosomal membrane with the limiting membrane
      of cellular endosomes, after internalization of the virosomes by receptor
      mediated endocytosis. It is concluded that virosomes represent a promising
      carrier system for cellular delivery of siRNA in vitro as well as in vivo.

PMID- 17454403
TI  - The DETECT system: portable, reduced-length neuropsychological testing for mild
      traumatic brain injury via a novel immersive environment.
AB  - Undiagnosed mild traumatic brain injury (mTBI) often leads to poor patient
      management and significant morbidity. The lack of an efficient screening tool is
      especially apparent in the athletic setting, where repetitive injuries can lead
      to prolonged disability. We have developed the Display Enhanced Testing for
      Concussions and mTBI system (DETECT), in order to create a portable immersive
      environment that could eliminate visual and audio distractions.
      Neuropsychological tests sensitive to mTBI were modified for use with the system
      and allow rapid neurological assessment independent of the environment or trained
      personnel. We evaluated the immersive qualities of the DETECT system in 42
      uninjured controls. The system was successful in blocking out external
      audiovisual stimuli. The neuropsychological test results obtained in a stimulus
      rich environment were equivalent to those obtained in a controlled quiet
      environment. The immersive environment, portability, and brevity of the DETECT
      system allow for real-time cognitive testing in situations previously deemed
      impractical or unavailable for mTBI patients.

PMID- 17454404
TI  - An improved design of axially driven permanent maglev centrifugal pump with
      streamlined impeller.
AB  - BACKGROUND: In 1839, Earnshaw proved theoretically that it is impossible to
      achieve a stable equilibrium with a pure permanent maglev. Furthermore, in 1939,
      Braunbeck deduced that it is only possible to stabilize a super conductive or an
      electric maglev. In 2000, however, the present authors discovered that stable
      levitation is achievable by a combination of permanent magnetic and nonmagnetic
      forces, and its stability can be maintained even with mere passive magnetic
      forces by use of the gyro-effect. DESIGN CONCEPTS: An improved design of
      permanent maglev impeller pump has been developed. Passive magnetic (PM) bearings
      support the rotor radially; on its right side, an impeller is fixed and on its
      left side a motor magnets-assemble is mounted. Unlike a previous prototype
      design, in which the rotor magnets were driven by a motor via magnetic coupling,
      a motor coil is installed opposite to the motor magnets disc, producing a
      rotating magnetic field. At standstill or if the rotating speed is lower than
      4000 rpm, the rotor has one axial point contact with the motor coil. The contact
      point is located at the centre of the rotor. As the rotating speed increases
      gradually to higher than 4000 rpm, the rotor will be drawn off from the contact
      point by the hydrodynamic force of the fluid. Then the rotor becomes fully
      suspended. KEY POINTS OF STABILIZATION: For radial and peripheral stabilization,
      a gyro-effect is important, which is realized by designing the motor magnets disc
      to have large diameter, short length and high rotating speed; for axial
      stability, an axial rehabilitating force is necessary, which is produced by PM
      bearings. RESULTS: The rotor demonstrated a full levitation by rotation over 4000
      rpm. As a left ventricular assist device, the rotation of the pump has a speed
      range from 5000 to 8000 rpm. The relation between pressure head and flow rate
      indicates that there is neither mechanical friction nor hydrodynamic turbulence
      inside the pump; the former is due to the frictionless maglev and the latter is a
      result of the streamlined design of the impeller.

PMID- 17454405
TI  - A four-generation Ehlers-Danlos syndrome with vascular dissections. Skin
      ultrastructure and biomechanical properties.
AB  - Ehlers-Danlos syndrome (EDS) is heterogenous with regard to genetic traits,
      clinical manifestation, the biomechanical and microscopic properties of
      connective tissues, and basic molecular defects. We report on nine relatives of
      four generations who suffered from large vessel dissections and cutaneous
      microscopic changes consistent with EDS. Measurements of the mechanical
      properties of skin were performed using a computerized suction device
      (Cutometer). Morphological and biomechanical alterations suggestive of EDS were
      present in all examined subjects. A loose network of collagen bundles was admixed
      with clumsy elastic fibres. Factor XIIIa-positive dermal dendrocytes looked
      almost normal but were slim and rarefied in four subjects. The severity in
      ultrastructural alterations of the collagen network differed among the subjects.
      The group with the most prominent changes showed the most striking biomechanical
      alterations characterized by increased biologic elasticity without any excess in
      skin extensibility. A positive correlation was found between skin extensibility
      and elasticity. In conclusion, distinct alterations in the collagen scaffolding
      were found to be correlated to variable severity in biomechanical alterations of
      the skin. The predictive value of these changes for large vessel dissections in
      some families at risk remains to be settled.

PMID- 17454406
TI  - World-smallest LVAD with 27 g weight, 21 mm OD and 5 l min-1 flow with 50 mmHg
      pressure increase.
AB  - To investigate the feasibility of a long-term left ventricular assist device
      (LVAD) placed in the aortic valve annulus, an implantable aortic valve pump (21
      mm outer diameter, weighing 27 g) was developed. The device consists of a central
      rotor and a stator. The rotor assembly incorporates driven magnets and an
      impeller. The stator assembly has a motor coil with an iron core and outflow
      guide vanes. The device is to be implanted identically to an aortic valve
      replacement, occupying no additional anatomic space. The pump delivers the blood
      directly from left ventricle to the aortic root, like a natural ventricle,
      therefore causing less physiologic disturbance to the natural circulation.
      Neither connecting conduits nor 'bypass' circuits are necessary. The pump is
      designed to cycle between a peak flow and zero net flow to approximate systole
      and diastole. Bench testing indicates that the pump can produce a blood flow of 5
      l min(-1) with 50 mmHg pressure increase at 17,500 rpm. At zero net flow rate,
      the pump can maintain a diastole aortic pressure against 80 mmHg at the same
      rotating speed.

PMID- 17454407
TI  - Visual evoked potential estimation by adaptive noise cancellation with neural
      network-based fuzzy inference system.
AB  - Visual evoked potentials (VEPs) are time-varying signals typically buried in
      relatively large background noise known as the electroencephalogram (EEG). In
      this paper, an adaptive noise cancellation with neural network-based fuzzy
      inference system (NNFIS) was used and the NNFIS was carefully designed to model
      the VEP signal. It is assumed that VEP responses can be modelled by NNFIS with
      the centres of its membership functions evenly distributed over time. The weights
      of NNFIS are adaptively determined by minimizing the variance of the error signal
      using the least mean squares (LMS) algorithm. As the NNFIS is dynamic to any
      change of VEP, the non-stationary characteristics of VEP can be tracked. Thus,
      this method should be able to track the VEP. Four sets of simulated data indicate
      that the proposed method is appropriate to estimate VEP. A total of 150 trials
      are processed to demonstrate the superior performance of the proposed method.

PMID- 17454408
TI  - Modified adaptive resonance theory based control strategy for EMG operated
      prosthesis for below-elbow amputee.
AB  - This paper presents a modified adaptive resonance theory (ART1)-based control
      strategy for a below-elbow (BE) prosthesis. The statistical parameters and
      histogram from two channels of an electromyogram (EMG) signal have been used as
      the feature space for the classification of four limb functions. The ART1 neural
      network (NN) has been used for the classification. ART1 has been modified to
      learn the patterns in supervised manner to suit the application. Further, the
      criteria for the modification of the stored pattern have been made bi-directional
      and the matching criteria have been designed for bit-by-bit matching. The major
      challenge of using ART1 is to decide on the value of the vigilance parameter, as
      the classification success is drastically affected by this parameter. The
      criteria have been evolved to get the optimal value of the vigilance parameter.
      It is concluded that the best value of vigilance parameter is that which provides
      the same tolerance in matching as the minimum bit distance between the stored
      patterns. This scheme has also been implemented on an 8031 microcontroller.

PMID- 17454409
TI  - Long-term ECG signal feature extraction.
AB  - This paper proposes a cepstrum coefficient method applying the dynamic time
      warping technique to extract the feature vectors from long-term ECG signals.
      Utilizing this method, one can identify the characteristics hidden in an ECG
      signal; and then classify the signal as well as diagnose the abnormalities. To
      evaluate this method, the Normal and PACED BEAT data from the MIT/BIH database
      are used. The results show that the proposed method successfully extracts the
      corresponding feature vectors, distinguishes the difference and classifies both
      signals.

PMID- 17454410
TI  - A new algorithm developed based on a mixture of spectral and nonlinear techniques
      for the analysis of heart rate variability.
AB  - In this paper, an algorithm based on a joint use of spectral and nonlinear
      techniques for heart rate variability (HRV) analysis is proposed. First, the
      measured RR data are passed into a trimmed moving average (TMA)-based filtering
      system to generate a lower frequency (LF) time series and a higher frequency (HF)
      one that approximately reflect the sympathetic and vagal activities,
      respectively. Since the Lyapunov exponent can be used to characterize the level
      of chaos in complex physiological systems, the largest Lyapunov exponents
      corresponding to the complex sympathetic and vagal systems are then estimated
      from the LF and HF time series, respectively, using an existing algorithm.
      Numerical results of a postural maneuver experiment indicate that both
      characteristic exponents or their combinations might serve as a set of innovative
      and robust indicators for HRV analysis, even under the contamination of sparse
      impulses due to aberrant beats in the RR data.

PMID- 17454411
TI  - Fuzzy entropy based interactive enhancement of radiographic images.
AB  - In certain radiographic images, fuzziness exists due to the vague nature of image
      characteristics and limitations of visual perception. Accordingly, a gap exists
      between the information content of an image and the information that can be
      retrieved. In this paper, a new fuzzy logic based intensification operator has
      been proposed for enhancement of images. For applying the operator effectively,
      selection of crossover point is critical. In this paper, the concept of fuzzy
      entropy has been proposed for objective selection of crossover point. Owing to
      semantic nature of information content, the methodology has a provision to change
      levels of enhancement interactively, to help in retrieving the information as
      required. The effectiveness of the methodology has been demonstrated. Comparison
      of the results with the Zadeh's INT operator and conventional histogram
      equalization techniques has established its superiority.

PMID- 17454416
TI  - Articulating and responding to uncertainties in clinical research.
AB  - This paper introduces taxonomy of clinical uncertaintes and argues that the
      choice of scientific method should match the underlying level of uncertainty.
      Clinical trial is one of these methods aiming to resolve clinical uncertainties.
      Whenever possible these uncertainties should be quantified. The paper further
      shows that the still ongoing debate about the usage of "equipoise" vs.
      "uncertainty principle" vs. "indifference" as an entry criterion to clinical
      trials actually refers to the question "whose uncertainty counts". This question
      is intimately linked to the control of research agenda, which is not quantifiable
      and hence is not solvable to equal acceptability to all interested parties. The
      author finally shows that there is a predictable relation between
      [acknowledgement of] uncertainty (the moral principle) on which trials are based
      and the ultimate outcomes of clinical trials. That is, [acknowledgement of]
      uncertainty determines a pattern of success in medicine and drives clinical
      discoveries.

PMID- 17454417
TI  - Two dogmas of research ethics and the integrative approach to human-subjects
      research.
AB  - This article argues that lingering uncertainty about the normative foundations of
      research ethics is perpetuated by two unfounded dogmas of research ethics. The
      first dogma is that clinical research, as a social activity, is an inherently
      utilitarian endeavor. The second dogma is that an acceptable framework for
      research ethics must impose constraints on this endeavor whose moral force is
      grounded in role-related obligations of either physicians or researchers. This
      article argues that these dogmas are common to traditional articulations of the
      equipoise requirement and to recently articulated alternatives, such as the non
      exploitation approach. Moreover, important shortcomings of these approaches can
      be traced to their acceptance of these dogmas. After highlighting these
      shortcomings, this article illustrates the benefits of rejecting these dogmas by
      sketching the broad outlines of an alternative called the "integrative approach"
      to clinical research.

PMID- 17454418
TI  - Equipoise and the duty of care in clinical research: a philosophical response to
      our critics.
AB  - Franklin G. Miller and colleagues have stimulated renewed interest in research
      ethics through their work criticizing clinical equipoise. Over three years and
      some twenty articles, they have also worked to articulate a positive alternative
      view on norms governing the conduct of clinical research. Shared presuppositions
      underlie the positive and critical dimensions of Miller and colleagues' work.
      However, recognizing that constructive contributions to the field ought to enjoy
      priority, we presently scrutinize the constructive dimension of their work. We
      argue that it is wanting in several respects.

PMID- 17454419
TI  - So-called "clinical equipoise" and the argument from design.
AB  - In this article, I review and expand upon arguments showing that Freedman's so
      called "clinical equipoise" criterion cannot serve as an appropriate guide and
      justification for the moral legitimacy of carrying out randomized clinical
      trials. At the same time, I try to explain why this approach has been given so
      much credence despite compelling arguments against it, including the fact that
      Freedman's original discussion framed the issues in a misleading way, making
      certain things invisible: Clinical equipoise is conflated with community
      equipoise, and several versions of each are also conflated. But a misleading
      impression is given that, rather than distinct criteria being arbitrarily
      conflated, a puzzle is solved and a number of features unified. Various issues
      are pushed under the rug, hiding flaws of the "clinical equipoise" approach and
      thus deceiving us into thinking that we have a solution when we do not.
      Particularly significant is the ignoring of the crucial distinction between the
      individual patient decision and the policy decision.

PMID- 17454420
TI  - Clinical equipoise and the incoherence of research ethics.
AB  - The doctrine of clinical equipoise is appealing because it appears to permit
      physicians to maintain their therapeutic obligation to offer optimal medical care
      to patients while conducting randomized controlled trials (RCTs). The appearance,
      however, is deceptive. In this article we argue that clinical equipoise is
      defective and incoherent in multiple ways. First, it conflates the sound
      methodological principle that RCTs should begin with an honest null hypothesis
      with the questionable ethical norm that participants in these trials should never
      be randomized to an intervention known to be inferior to standard treatment.
      Second, the claim that RCTs preserve the therapeutic obligation of physicians
      misrepresents the patient-centered orientation of medical care. Third, the appeal
      to clinical equipoise as a basic principle of risk-benefit assessment for RCTs is
      incoherent. Finally, the difficulties with clinical equipoise cannot be resolved
      by viewing it as a presumptive principle subject to exceptions. In the final
      sections of the article, we elaborate on the non-exploitation framework for the
      ethics clinical research and indicate issues that warrant further inquiry.

PMID- 17454421
TI  - The irrelevance of equipoise.
AB  - It is commonly believed in research ethics that some form of equipoise is a
      necessary condition for justifying randomized clinical trials, that without it
      clinicians are violating the moral duty to do what is best for the patient.
      Recent criticisms have shown how complex the concept of equipoise is, but often
      retain the commitment to some form of equipoise for randomization to be
      justified. This article rejects that claim. It first asks for what one should be
      equally poised (scientific or clinical equipoise), then asks who should be
      equally poised (scientist, clinician, or subject), and finally asks why any of
      these players need be equally poised between treatment options. The article
      argues that only the subject's evaluation of the options is morally relevant and
      that even the subject need not be equally poised or indifferent between the
      options in order to volunteer for randomization. All that is needed is adequately
      informed, free, and unexploited consent. It concludes equipoise is irrelevant.

PMID- 17454422
TI  - Microcapsule-gel formulation of promethazine HCl for controlled nasal delivery: a
      motion sickness medication.
AB  - The current method of choice for astronauts to treat space motion sickness is an
      intra-muscular injection of promethazine hydrochloride (PMZ HCl) which is
      invasive and causes considerable local irritation and discomfort at the site of
      injection. Intra-nasal delivery is considered a feasible alternative route for
      administration of medications to treat space motion sickness. The purpose of this
      research is to develop a PMZ HCl formulation that can be administered intra
      nasally without irritation (i.e. leukocyte infiltration) in the nasal epithelium
      when dosed at PMZ HCl concentrations greater than the cytotoxic limit. The
      biocompatibility of PMZ HCl was tested in vitro and was shown to be cytotoxic at
      concentrations greater than 10(-5) molar regardless of pH. A controlled-release
      microencapsulated dosage formulation was developed using spinning disk
      atomization and release rates for the PMZ HCl microcapsules were determined in
      phosphate buffered saline. An animal study was conducted to determine the
      irritation response of rat nasal mucosa when dosed with encapsulated and non
      encapsulated PMZ HCl.

PMID- 17454423
TI  - Effect of poly(lactide-co-glycolide) molecular weight on the release of
      dexamethasone sodium phosphate from microparticles.
AB  - The objective of this study was to investigate the effect of poly(lactide-co
      glycolide) (PLGA) molecular weight (Resomer RG 502H, RG 503H, and RG 504H) on the
      release behavior of dexamethasone sodium phosphate-loaded microparticles. The
      microparticles were prepared by three modifications of the solvent evaporation
      method (O/W-cosolvent, O/W-dispersion, and W/O/W-methods). The encapsulation
      efficiency of microparticles prepared by the cosolvent- and W/O/W-methods
      increased from approximately 50% to >90% upon addition of NaCl to the external
      aqueous phase, while the dispersion method resulted in lower encapsulation
      efficiencies. The release of dexamethasone sodium phosphate from PLGA
      microparticles (>50 microm) was biphasic. The initial burst release correlated
      well with the porosity of the microparticles, both of which increased with
      increasing polymer molecular weight (RG 504H > 503H > 502H). The burst was also
      dependent on the method of preparation and was in the order of dispersion method
      > WOW method > consolvent method. In contrast to the higher molecular weight PLGA
      microparticles, the release from RG 502H microparticles prepared by cosolvent
      method was not affected by volume of organic solvent (1.5-3.0 ml) and drug
      loading (4-13%). An initial burst of approximately 10% followed by a 5-week
      sustained release phase was obtained. Microparticles with a size <50 microm
      released in a triphasic manner; an initial burst was followed by a slow release
      phase and then by a second burst.

PMID- 17454424
TI  - Thrombin receptor agonist peptide entrapped in poly(D,L)-lactide-co-glycolide
      microparticles: preparation and characterization.
AB  - Thrombin receptor agonist peptide (TRAP-6) could advantageously replace thrombin
      in terms of accelerating wound healing being less expensive and more stable. To
      promote TRAP-6 pharmacological action as a tissue reconstruction stimulator this
      study investigated its entrapment within poly(D,L)-lactide-co-glycolide (PLGA)
      microparticles. Due to its low molecular weight and water solubility, TRAP-6
      microencapsulated form is expected to be more useful. This paper reports TRAP-6
      microencapsulation by a double (w/o/w) emulsion-evaporation technique. TRAP-6
      release kinetics were evaluated by both chemical (HPLC) and biological assays in
      vitro. The results revealed a high level of TRAP-6 sensitivity to physico
      chemical events during the microencapsulation. The surface morphology difference
      between control microparticles (without TRAP-6) and microparticles with entrapped
      TRAP-6 during in vitro degradation highlighted a particular role of TRAP-6. The
      results can allow one to optimize the microencapsulation procedure and to
      encounter a new promising approach to development of biodegradable polymer drug
      delivery systems for wound healing.

PMID- 17454425
TI  - Electrosprayed bovine serum albumin-loaded tripolyphosphate cross-linked chitosan
      capsules: synthesis and characterization.
AB  - Bovine serum albumin (BSA)-loaded tripolyphosphate (TPP) cross-linked chitosan
      capsules were prepared using an electrospraying technique, in which a
      sufficiently strong electric field was applied to overcome the surface tension of
      a droplet. A comprehensive investigation was conducted on the effects of
      concentrations of initial chitosan and TPP solutions, flow rate and BSA/chitosan
      weight ratio on the physical properties of the mixtures; the morphology, size and
      yield of the capsules; BSA encapsulation efficiency (EE) and loading capacity
      (LC); and in vitro release. A high voltage was required to obtain a continuous
      and stable spray for the mixtures with a high viscosity at high chitosan
      concentration. The capsules were spherical in shape. Capsule size increased with
      increasing flow rate, but did not change significantly (p < 0.05) with increases
      in concentrations of chitosan and TPP. Increasing concentrations of chitosan and
      TPP solutions increased the yields, while yields decreased with increases in the
      flow rate. EE and LC increased with increasing chitosan concentration,
      BSA/chitosan weight ratio and TPP concentration and decreased with increasing
      flow rate. High EE enhanced the BSA release rate, while a high degree of cross
      linking slowed its release.

PMID- 17454426
TI  - Effect of process variables on particle size and viability of Bifidobacterium
      lactis Bb-12 in genipin-gelatin microspheres.
AB  - Gelatin microspheres cross-linked with genipin were developed to encapsulate the
      probiotic Bifidobacterium lactis Bb-12 The effects of different gelatin
      concentrations (10-19% w/v), bloom strengths (175 and 300), surfactants, stirring
      rates during emulsion formation and genipin concentrations (0-10 mM) on the
      microsphere sizes and viability of bacterial cells were investigated. Principal
      Component Analysis revealed microsphere size distribution differed depending on
      the presence or absence of surfactants as well as a trend of increasing
      micropshere size with increasing gelatin concentration and bloom strength. Lower
      stirring rates resulted in larger microspheres with higher encapsulation yields
      of bifidobacteria Microsphere size and cell viability were not significantly (p <
      0.05) influenced by increasing genipin concentrations up to 10 mM whereas
      microsphere stability in simulated gastric juice increased with increasing
      genipin concentration. The encapsulation yields were higher in 175 bloom strength
      gelatin microspheres than in 300. Cold-stage scanning electron microscopy showed
      encapsulated bacteria distributed throughout the genipin cross-linked gelatin
      matrix.

PMID- 17454427
TI  - Cartilage regeneration using a novel gelatin-chondroitin-hyaluronan hybrid
      scaffold containing bFGF-impregnated microspheres.
AB  - Cartilage engineered from chondrocytes requires a scaffold to keep the cells in
      the cartilage defect and to act as a support for inducing hyaline cartilage
      formation on occasion. In this study, we developed a novel three-dimensional
      special scaffold in combination with a controlled release of bFGF, which provided
      structural support and stimulated repair. Gelatin microspheres loaded with bFGF
      (GM-bFGF) showed a fast release at the initial phase (28.23%) and the ultimate
      accumulated release was 92.9% by day 14. Three-dimensional gelatin-chondroitin
      hyaluronan hybrid scaffolds seeded with cultured autologous chondrocytes were
      transplanted into the defects in rabbit knees and analyzed histologically at 12
      and 24 weeks after the operation. Our findings showed that the defects were
      filled with smooth, shiny white cartilaginous tissue macroscopically and hyaline
      like cartilage histologically 24 weeks postoperatively. The present study implied
      the great potential of the novel scaffold with GM-bFGF as a new way to promote
      the retention of chondrocytes and it might serve as a desirable cartilaginous
      tissue scaffolds to enhance the chondrogenesis.

PMID- 17454429
TI  - Literature alerts.

PMID- 17454428
TI  - Microparticles prepared with poly(hydroxybutyrate-co-hydroxyvalerate) and
      poly(epsilon-caprolactone) blends to control the release of a drug model.
AB  - The objective of this work was to verify the influence of the poly(epsilon
      caprolactone) PCL concentration in poly(hydroxybutyrate-co-hydroxyvalerate)
      P(HBHV)/PCL microparticles, prepared by an emulsion/solvent evaporation process,
      on the release behavior of a drug. Differential Scanning Calorimetry analyses
      demonstrated that the preparation process increased the crystallite heterogeneity
      for the P(HBHV) in the particles. The drug caused an increase in the glass
      transition of the P(HBHV) in the microparticles. Dexamethasone acetate-loaded
      microparticles demonstrated drug sustained releases (up to 250 h), which profiles
      fit the biexponential model. The release of dexamethasone acetate caused an
      increase in the surface area of the microparticles. The kinetic constants of the
      sustained phase increased with the augmentation of the PCL content in the blend.
      The drug release mechanism was dependent on the presence of PCL in the
      microparticles. A Fickian release was determined for the microparticles prepared
      exclusively with P(HBHV), while non-Fickian release behaviors were found for the
      P(HBHV)/PCL microparticles.

PMID- 17454432
TI  - Comparison of alpha-tocopherol microparticles produced with different wall
      materials: pea protein a new interesting alternative.
AB  - Alpha-tocopherol is a radical chain breaking antioxidant that can protect the
      integrity of tissues and play an important role in life process. Microparticles
      containing alpha-tocopherol were produced by spray drying technique using pea
      protein (PP), carboxymethylcellulose(CMC) and mixtures of these materials with
      maltodextrin (PP-M and CMC-M) as wall materials. The microparticles produced were
      characterised as regards the core retention (high performance liquid
      chromatography), the morphology (scanning electron microscopy) and size
      distribution (laser diffraction). The retention of alpha-tocopherol within all
      microparticles was above 77%. They showed a spherical shape and roughness at
      varied degrees. Their mean particles size remained below 7 microm, and the
      smallest sizes were found in PP and CMC-M microparticles. The results obtained in
      this work show that the pea protein use for alpha-tocopherol microencapsulation
      is a promising system for further application in food.

PMID- 17454433
TI  - Effects of different cyclodextrins on the morphology, loading and release
      properties of poly (DL-lactide-co-glycolide)-microparticles containing the
      hypnotic agent etizolam.
AB  - The aim of this study was to gain insight into the feasibility of using
      microparticles (MPs) constituted by the biodegradable poly (DL-lactide-co
      glycolide) (PLGA) and a number of cyclodextrins (CDs) as an orally sustained
      delivery system of the hypnotic agent etizolam (ETZ). A further aim of the work
      was to investigate the effects of different CDs on the morphology, loading, and
      release properties of the MPs prepared. For these purposes, ETZ alone, and ETZ/CD
      PLGA loaded MPs were prepared by the W/O/W emulsion-solvent evaporation method.
      It was found that the release of ETZ in vitro was more prolonged over three days
      with a kinetic constant proportional to t(1/2). It was also demonstrated that the
      CDs in these MPs are able to modulate several properties such as morphology, drug
      loading, and release properties. In fact, marked differences in shape, surface,
      and encapsulation efficiencies were noted depending on the presence,
      hydrophilicity, and charge of the CD employed. The obtained results induce us to
      consider the present ETZ-containing formulations as new valuable tools for the
      treatment of different insomnia categories.

PMID- 17454434
TI  - Preparation and release characteristics of insulin and insulin-like growth factor
      one from polymer nanoparticles.
AB  - Two methods of preparing polymer nanoparticles containing (a) insulin and (b)
      insulin-like growth factor-1 were compared and the influence of process
      parameters on size and release characteristics was determined. Poly(lactide
      glycolide)co-polymer (50:50) was used in both methods. Method one used a salting
      out process; while method two used a solvent evaporation/double emulsion
      procedure forming a w/o/w secondary emulsion. Particles were separated by
      centrifugation and dried under vacuum. Particle size was analysed by scanning
      electron microscopy and protein release by dissolution and high pressure liquid
      chromatography. Method one produced particles of diameter 0.3-0.8 microm, whereas
      method two gave larger particles of 0.76-1.05 microm and in both procedures
      reducing pH also decreased particle size. Optimal emulsifying speed was below 4
      000 rpm and scanning electron micrographs showed smooth spherical particles.
      Release characteristics of insulin and IGF-1 in method one and two were similar
      releasing 60% in 10 days but in method one release was diminished to 8% over a
      similar time period. Method one proved successful in producing spheres of the
      required size range but hampered protein loading by denaturation resulting in a
      low release rate. Method two provided an acceptable release rate but produced
      particles with diameters of about one micron.

PMID- 17454435
TI  - Formulation and evaluation of an oral melanoma vaccine.
AB  - The purpose of this study was to formulate and evaluate the physicochemical
      properties and efficacy of an oral melanoma vaccine. Blood, feces and vaginal
      wash were collected weekly and analysed by ELISA. The mortality and diameter of
      the tumors were determined using a vernier caliper. The oral melanoma vaccine
      microparticles demonstrated desirable particle size, product yield, and zeta
      potentials. In addition, FT-IR and DSC studies revealed that there was no
      significant degradation in microencapsulated extra-cellular antigen (ECA). The
      oral vaccine group showed 25% greater survival rate compared to the control in
      the efficacy and challenge studies.

PMID- 17454436
TI  - Development and characterization of floating microballoons for oral delivery of
      cinnarizine by a factorial design.
AB  - Cinnarizine (CN) is a pipperazine derivative with anti-histaminic activity and
      high affinity to H(1) receptors. The objective of this study was to produce
      floating microspheres (FM) of CN by diffusion solvent evaporation technique to
      increase drug solubility and hence its bioavailability. The effect of process
      variables such as: Eudragit type, stirring rate and time of stirring after
      addition of oily phase to the aqueous phase were evaluated on the yield, particle
      size, loading, release and floating behaviors of microspheres using a factorial
      design. Release of CN from microspheres was studied in pHs: 1.2 and 7.2 using
      paddle technique. The samples of dissolution test were analysed
      spectrophotometrically at 256.1 nm and 256.5 nm respectively. particle size of
      microspheres was studied using microscopic method and their floating behavior was
      studied in HCl (0.1 N, pH 1.2) medium with Tween 20 (0.5% w/v). Eight
      formulations were produced by changing 3 variables each at 2 levels: Eudragit
      S100 (Ps) or a combination of two Eudragits S100:RLPO (1:3) (P(SR)), stirring
      rate of 200 (R(2)) or 300 rpm (R(3)) and stirring time after addition of oily
      phase to the aqueous phase 0 (T(0)) or 1 hr (T(1)). The average size of
      microspheres was 300 microm. The highest yield efficiency (94%) was seen in
      P(SR)R(3)T(0) formulation and the greatest loading percentage was 8.5% in
      P(SR)R(2)T(1) formulation. The microspheres containing just Eudragit S100, didn't
      show suitable releasing profile during 8 hours in pH 1.2 but those containing
      combination of Eudragit S100:RL released approximately whole amount of CN during
      10 hours (8 hours in pH 1.2 and 2 hours in pH 7.2). The highest floating
      percentage up to 6 hours was 77.5% in P(S)R(2)T(1) formulation. The type of
      Eudragit used seems to play an important role in producing sustained release
      floating microspheres. P(SR)R(3)T(0) formulation containing both types of
      Eudragit S100:RL (1.3) that releases 99.1% of the drug after 10 hours and 65%
      floating after 6 hr seems suitable for oral sustained delivery of CN.

PMID- 17454437
TI  - Effect of the dispersion of Eudragit S100 powder on the properties of cellulose
      acetate butyrate microspheres containing theophylline made by the emulsion
      solvent evaporation method.
AB  - The dispersion/incorporation of Eudragit S100 powder as a filler in cellulose
      acetate butyrate (CAB-551-0.01) microsphere containing theophylline was
      investigated as a means of controlling drug release. Microspheres of CAB-551-0.01
      of different polymer solution concentrations/viscosities were prepared
      (preparations Z(0), Z(A), Z(B) and Z(C)) and evaluated and compared to
      microspheres of a constant concentration of CAB-551-0.01 containing different
      amounts of Eudragit S100 powder as a filler (preparations X(A), X(B) and X(C)).
      The organic solvent acetonitrile used was capable of dissolving the matrix former
      CAB-551-0.01 only but not Eudragit S100 powder in the emulsion-solvent
      evaporation method. The CAB-551-0.01 concentration in Z(A), Z(B) and Z(C) was
      equal to the total polymer concentration (CAB-551-0.01 and Eudragit S100 powder)
      in X(A), X(B) and X(C), respectively. Scanning electron microscopy (SEM) was used
      to identify microspheres shape and morphology. In vitro dissolution studies were
      carried out on the microspheres at 37 degrees C (+/-0.5 degrees C) at two
      successive different pH media (1.2 +/- 0.2 for 2 h and 6.5 +/- 0.2 for 10 h). Z
      preparations exhibited low rates of drug release in the acidic and the slightly
      neutral media. On the other hand, X preparations showed an initial rapid release
      in the acidic medium followed by a decrease in the release rate at the early
      stage of dissolution in the slightly neutral pH which could be due to some
      relaxation and gelation of Eudragit S100 powder to form a gel network before it
      dissolves completely allowing the remained drug to be released.

PMID- 17454440
TI  - Literature alerts.

PMID- 17454438
TI  - Novel hydrogel microspheres of chitosan and pluronic F-127 for controlled release
      of 5-fluorouracil.
AB  - Hydrogel microspheres of chitosan (CS) and Pluronic F127 (PF-127) were prepared
      by the emulsion-crosslinking method employing glutaraldehyde (GA) as a
      crosslinker. 5-Fluorouracil (5-FU), an anticancer drug with good water
      solubility, was encapsulated into hydrogel microspheres. Various formulations
      were prepared by varying the ratio of CS and PF-127, % drug loading and amount of
      GA. Microspheres were characterized by Fourier transform infrared (FTIR)
      spectroscopy to confirm the absence of chemical interactions between drug,
      polymer and the crosslinking agent. Scanning electron microscopy (SEM) was
      performed to study the surface morphology of the microspheres. SEM showed that
      microspheres have smooth shiny surfaces. Particle size, as measured by laser
      light scattering technique, gave an average size ranging from 110 to 382 microm.
      Differential scanning calorimetry (DSC) and X-ray diffraction (X-RD) studies were
      performed to understand the crystalline nature of the drug after encapsulation
      into hydrogel microspheres. Encapsulation of the drug up to 86% achieved was
      measured by UV spectroscopy. Equilibrium swelling experiments were performed in
      distilled water. Diffusion coefficients (D) of water through microspheres were
      estimated by an empirical equation. In vitro release studies indicated the
      dependence of release rate on the extent of crosslinking, drug loading and the
      amount of PF-127 used to produce the microspheres; slow release was extended up
      to 24 h. The release data were also fitted to an empirical equation to compute
      the diffusional exponent (n), which indicated that the release mechanism followed
      the non-Fickian trend.

PMID- 17454444
TI  - Simian fetal brain progenitor cells for studying viral neuropathogenesis.
AB  - The pathogenesis of neurologic dysfunctions caused by human immunodeficiency
      virus type 1 (HIV-1) infection is not yet well understood. Simian
      immunodeficiency virus (SIV) infection of macaques is an important animal model
      for HIV-1 infection. This is the first report to characterize brain progenitor
      cells (BPCs) isolated from embryonic brain of cynomolgus monkeys (Macaca
      fascicularis) by neurosphere assay and utilize BPC-derived cell culture for
      studying SIV infection. The self-renewal and multilineage differentiation
      properties of BPCs are convenient for planning viral infection experiments. The
      BPC-derived culture does not contain macrophage/microglial cells, fibroblasts, or
      endothelial cells. Thus, this culture is appropriate for studying direct relation
      between SIV infection and neuronal and glial cells. First, the authors
      characterized undifferentiated and differentiated simian BPCs by
      immunocytochemistry, flow cytometry analysis, real-time polymerase chain reaction
      (PCR), and reverse transcriptase (RT)-PCR. The BPCs induced to differentiate by
      the addition of 1% fetal bovine serum (FBS) were composed of heterogeneous cells
      expressing nestin, glial fibrillary acidic protein (GFAP), and/or tubulin beta
      III isoform (Tuj). None of them expressed the monocyte/macrophage/microglial
      marker. mRNA expression of CD4, CXCR4, CCR5, GPR1, STRL33, and APJ in both
      undifferentiated and differentiated BPCs were shown by RT-PCR method, suggesting
      that SIV would infect and replicate in this culture system. Then, it was
      confirmed that the neurotropic SIV strain, SIV17/E-Fr, replicated productively in
      BPC-derived cells. The SIV/17E-FrDelta nefGFP was inoculated to identify the
      infected cells and immunocytochemistry analysis revealed that green fluorescent
      protein (GFP)-expressing cells were mostly GFAP positive and coexpressed with SIV
      p27 antigen. Thus, BPC-derived cell culture system is applicable for studying SIV
      infection in glial and neuronal cells.

PMID- 17454445
TI  - Neuropathologic confirmation of definitional criteria for human immunodeficiency
      virus-associated neurocognitive disorders.
AB  - Research findings have suggested a need for modifications to the original
      nomenclature for human immunodeficiency virus (HIV)-associated neurocognitive
      disorders issued in 1991 by the American Academy of Neurology (AAN). The HIV
      Neurobehavioral Research Center (HNRC) proposed a diagnostic scheme that departs
      from the AAN 1991 criteria primarily in the inclusion of an asymptomatic
      neurocognitive impairment (ANI) category that relies on cognitive disturbances as
      a necessary criterion for diagnosis, without requiring declines in daily
      functioning, motor, or other behavioral abnormalities. In order to test the
      predictive validity of these two nomenclatures, the authors compared the
      correspondence between antemortem neurocognitive diagnoses resulting from AAN and
      HNRC criteria to a neuropathological diagnosis of HIV encephalitis (HIVE) made at
      autopsy. Agreement between the two sets of definitional criteria was 79%
      regarding the classification of cases as either neurocognitively normal or
      impaired, and 54% with regard to specific neurocognitive diagnoses. When
      pathological evidence of HIVE was considered as the external indicator of HIV
      related brain involvement, 64% of cases were correctly classified by AAN
      criteria, compared to 72% by HNRC criteria. HNRC criteria had better positive
      predictive power (95% versus 88%), sensitivity (67% versus 56%), and specificity
      (92% versus 83%). Three cases with HIVE and were correctly identified by HNRC
      criteria for ANI but called normal by AAN criteria, supporting inclusion of an
      asymptomatic neurocognitive condition. The modifications to the AAN 1991 criteria
      proposed by the HNRC and others in the field have served as a point of departure
      for a recently revised consensus nomenclature.

PMID- 17454443
TI  - Glial activation and matrix metalloproteinase release in cerebral malaria.
AB  - Although neurological symptoms associated with cerebral malaria (CM) are largely
      reversible, recent studies suggest that lasting neurological sequelae can occur.
      This may be especially true for children, in whom persistent deficits include
      problems with memory and attention. Because the malaria parasite is not thought
      to enter the brain parenchyma, lasting deficits are likely related to factors
      including the host response to disease. Studies with a rodent model, and with
      human postmortem tissue, suggest that glial activation occurs with CM. In this
      review, the authors will highlight studies focused on such activation in CM.
      Likely causes will be discussed, which include ischemia and activation of blood
      brain barrier endothelial cells. The potential consequences of glial activation
      will also be discussed, highlighting the possibility that glial-derived
      proteinases contribute to structural damage of the central nervous system (CNS).
      Of note, for the purposes of this focused review, glial activation will refer to
      the activation of astrocytes and microglial cells; discussion of oligodendroglial
      cells will not be included. In addition, although events thought to be critical
      to the pathogenesis of CM and glial activation will be covered, a comprehensive
      review of cerebral malaria will not be presented. Excellent reviews are already
      available, including Coltel et al (2004; Curr Neurovasc Res 1: 91-110), Medana
      and Turner (2006; Int J Parasitol 36: 555-568), and Hunt et al (2006; Int J
      Parasitol 36: 569-582).

PMID- 17454446
TI  - Influenza A virus transactivates the mouse envelope gene encoding syncytin B and
      its regulator, glial cells missing 1.
AB  - Recently, two candidate analogs for human syncytin, denoted syncytins A and B,
      were identified in the murine genome. These were found to have expression
      patterns and functions similar to human syncytin. In addition, the identification
      of glial cells missing (GCM)-binding motifs in putative promoter regions of the
      mouse syncytins imply analogous regulation. Transcriptional modulation of
      syncytin by exogenous agents was recently suggested by studies reporting
      transactivation of syncytin in human cell lines following virus infections. The
      authors report that influenza A virus infection increased the levels of
      transcripts encoding Gcm1 and syncytin B, but not syncytin A, in NIH-3T3 cells as
      well as in mouse primary neurons or glia. Overexpression of human GCM1 in NIH-3T3
      cells resulted in increased levels of transcripts encoding syncytin B but not
      syncytin A. Systemic administration of neurotropic influenza A virus resulted in
      a neuronal infection and increased levels of Gcm1-encoding transcripts in brains
      of young mice. The mouse may therefore be useful for studies on the expression
      and function of endogenous retroviral envelope genes and transcription factors
      regulating their expression in the placenta and brain during physiological or
      pathological conditions.

PMID- 17454447
TI  - Aquaporin 4 regulation during acute and long-term experimental Herpes simplex
      virus encephalitis.
AB  - Structural damage of the central nervous system (CNS) often leads to severely
      disabling residual symptoms despite effective antiviral therapy during Herpes
      simplex virus encephalitis (HSVE). Edematous space-occupying lesions are
      pathological and neuroradiological well-known phenomena for this disease. The
      molecular mechanisms of brain edema development in HSVE are poorly understood,
      the regulation of water brain-blood barrier (BBB) permeability might be
      disturbed. Aquaporin 4 (AQP4) is the predominant aquaporin expressed in the
      brain. Aquaporin 1 (AQP1) plays a role in cerebrospinal fluid modulation.
      Previous studies suggest that alterations of AQP expression play an important
      role in the development of brain edema. The mRNA expression of AQP4, AQP1, of
      their physiologically associated proteins Alpha-syntrophin and KIR 4.1 and of the
      structural glial protein glial fibrillary acid protein (GFAP) was analyzed in a
      well-established mice model simulating the human disease. Our data demonstrate a
      significant down-regulation of AQP4 in the acute phase of disease and an up
      regulation of AQP4 and AQP1 in the long term. These results reveal the complex
      transcription pattern of AQP4, AQP1, KIR 4.1, alpha-syntrophin, and GFAP during
      HSVE and suggest a role for AQP4 regulation in the pathophysiology of acute and
      long-term HSVE. AQP4 modulation could be a potential target for brain edema
      treatment during HSVE.

PMID- 17454448
TI  - Theiler's virus strain-dependent induction of innate immune responses in RAW264.7
      macrophages and its influence on viral clearance versus viral persistence.
AB  - Infection of susceptible mice with the DA strain of Theiler's murine
      encephalomyelitis virus (TMEV) induces a persistent central nervous system
      infection accompanied by demyelination that resembles multiple sclerosis. In
      contrast, Theiler's GDVII strain does not persist, because infected animals
      either clear the virus or die. Previously, the authors have shown that in vitro
      infection of RAW264.7 macrophages displays a similar strain-dependent outcome,
      resulting in the establishment of a persistent infection with the DA strain and
      clearance of the GDVII strain. Here, the authors show that when RAW264.7 cells
      were infected with both strains, the antiviral response triggered by the GDVII
      virus interfered with the DA virus' ability to induce a persistent infection.
      Treatment of cells with 2-aminopurine, a protein kinase R inhibitor, increased
      GDVII virus yields in contrast to DA virus yields. By comparing the antiviral
      activity of RAW264.7 macrophages against TMEV, it was found that GDVII-infected
      macrophages mounted a five times more potent antiviral response than the DA
      infected ones, indicating that there are strain-dependent differences in the
      induction of host innate immune responses. Measurements of interferon (IFN)
      production confirmed this finding. In addition, it was found that the
      macrophages' antiviral response is dependent on the multiplicity of infection.
      The antiviral activity resulting from GDVII-infected macrophages could be
      partially neutralized with antibodies against IFN-alpha or IFN-gamma, but not
      with an anti-IFN-beta antibody. Because only a partial neutralization was
      reached, the authors speculate that apart from the investigated IFNs, other
      cellular factors contribute to the observed antiviral activity. Taken together,
      these results demonstrate the importance of host innate immune responses in
      determining the balance between viral clearance and viral persistence.

PMID- 17454449
TI  - The latency-associated transcript of herpes simplex virus type 1 promotes
      survival and stimulates axonal regeneration in sympathetic and trigeminal
      neurons.
AB  - Herpes simplex virus type 1 (HSV-1) primarily infects mucoepithelial tissues of
      the eye, the orofacial region, and to a lesser extent the genitalia. The virus is
      retrogradely transported through the axons of sensory and sympathetic neurons to
      their cell bodies to establishe a life-long latent infection. Throughout this
      latency period, the viral genome is transcriptionally silent except for a single
      region encoding the latency-associated transcript (LAT). The function of LAT is
      still largely unknown. To understand how HSV-1 latency might affect neurons, the
      authors transfected primary cultures of sympathetic neurons and trigeminal
      sensory neurons obtained from rat embryos with LAT-expressing plasmids. LAT
      increased the survival of both sympathetic and trigeminal neurons after induction
      of cell death by nerve growth factor (NGF) deprivation. Because HSV-1 is
      transported through axons both after initial infection and during reactivation,
      the authors considered the possibility that LAT may affect axonal growth. They
      found that LAT expression increased axonal regeneration by twofold in both types
      of neurons. Inhibition of the mitogen-activated protein kinase (MAPK) pathway
      reverses stimulation of both neuronal survival and axonal regeneration, which
      indicates that these effects are mediated through the MAPK pathway. These data
      provide evidence that HSV-1 LAT promotes survival of sympathetic as well as
      trigeminal neurons. The authors show for the first time that LAT stimulates
      axonal regeneration in both sympathetic and trigeminal neurons.

PMID- 17454450
TI  - Neurological evaluation of untreated human immunodeficiency virus infected adults
      in Ethiopia.
AB  - Human immunodeficiency virus (HIV) has been implicated in neurological
      complications in developed countries. Developing countries have different viral
      clades and potentially different genetic and social risks for these
      complications. Baseline neurological performance measures associated with HIV
      infection have rarely been available from developing countries. The authors
      carried our a cross-sectional neurological evaluation of a cohort of community
      dwelling treatment-naive HIV-infected patients and similar control subjects from
      the same communities in Ethiopia. Blinded evaluation using standardized
      structured questionnaires and a neurological examination was performed by
      neurologists and treating physicians trained by an HIV neurology specialist.
      Quantitative performance measures for cognitive and motor function were employed.
      Data were analyzed with descriptive statistical methods, standard contingency
      table methods, and nonparametric methods. HIV-positive and control groups were
      similar by age, gender, and job site. Participants included 73 HIV-positive and
      87 HIV-negative controls. Fingertapping speed in the dominant hand was more
      poorly performed in HIV positives than negatives (P = .01) and was significantly
      associated with HIV viral load levels (P = .03). Other quantitative
      neuropsychiatric tests including timed gait, grooved pegboard, task learning, and
      animal naming did not show significant differences between the two groups. The
      overall prevalence of central nervous system (CNS) and/or peripheral nervous
      system (PNS) disease did not significantly differ in the two populations. HIV
      patients had slowed fingertapping speed correlating with viral load. Other
      measures of CNS and/or peripheral nervous performance did not differ from
      controls. The unanticipated minor evidence of HIV-associated neurocognitive and
      peripheral nerve deficits in this untreated HIV-positive population invite
      further investigation.

PMID- 17454451
TI  - JC virus viremia in interferon-beta -treated and untreated Italian multiple
      sclerosis patients and healthy controls.
AB  - Following the development of progressive multifocal leukoencephalopathy (PML) in
      two multiple sclerosis (MS) patients treated with natalizumab and interferon-beta
      (IFNbeta), a possible correlation between JC virus (JCV), the etiological agent
      of PML, and MS has received heightened interest. In particular, attention has
      focused on assessing whether IFNbeta treatment could affect the replication of
      JCV and thus its frequency in the peripheral blood of MS patients and whether the
      presence of JCV DNA in peripheral blood could be a predictive marker of the risk
      of developing PML. In order to answer to these questions, peripheral blood
      samples were collected from 59 INFbeta-treated, 39 untreated relapsing-remitting
      MS patients, and 98 healthy controls (HCs) and JCV DNA levels were determined and
      quantified by means of a real-time polymerase chain reaction (Q-PCR) assay.
      Overall, no differences were found in the presence or viral load of JCV DNA of MS
      patients and the HCs, but JCV DNA was significantly less frequent in the
      peripheral blood of IFNbeta-treated patients (13.6%) compared to the untreated MS
      patients (46.1%) and the healthy controls (28.6%). These results suggest that the
      presence of JCV in the blood of MS patients cannot be considered as a marker or a
      risk factor for PML development. In addition, they indicate that treatment with
      INFbeta can lead to the reduction of presence of the JCV genome in the peripheral
      blood of MS patients and, thus, that this drug probably does not increase the
      risk of PML in MS patients treated with IFNbeta.

PMID- 17454453
TI  - RE: "Lack of association of herpesviruses with brain tumors".

PMID- 17454452
TI  - Reactivation phenotype in rabbits of a herpes simplex virus type 1 mutant
      containing an unrelated antiapoptosis gene in place of latency-associated
      transcript.
AB  - Latency-associated transcript (LAT) significantly enhances the spontaneous
      reactivation phenotype of herpes simplex virus type 1 (HSV-1). The mechanism by
      which LAT accomplishes this has been elusive. To determine if LAT's antiapoptosis
      activity is involved, the authors used a rabbit eye model to analyze the
      spontaneous reactivation phenotype of an HSV-1 mutant in which LAT was replaced
      by an unrelated antiapoptosis gene. This virus, dLAT-cpIAP, contains the open
      reading frame of the baculovirus inhibitor of apoptosis protein gene (cpIAP) in
      place of LAT, under control of the LAT promoter. The authors report here that in
      a rabbit ocular model of infection, dLAT-cpIAP had a spontaneous reactivation
      phenotype similar to wild-type virus and significantly higher than LAT(-)
      viruses. This was consistent with their previous findings using the mouse
      trigeminal ganglia explant-induced reactivation model. Whether LAT (and in the
      case of dLAT-cpIAP, cpIAP) enhances the spontaneous reactivation phenotype by
      functioning during establishment of latency, maintenance of latency, or
      reactivation from latency, or during two or more of these periods, remains to be
      determined. Regardless, the results presented in this study strongly support the
      hypothesis that LAT's antiapoptosis activity is the dominant function that
      enhances HSV-1's spontaneous reactivation phenotype.

PMID- 17454455
TI  - Therapeutic options in the polycystic ovary syndrome.
AB  - The polycystic ovary syndrome is the most common endocrine disorder affecting
      women. It is a heterogeneous familial condition of uncertain aetiology. The
      diagnosis is made by the detection of polycystic ovaries on ultrasound
      examination and the occurrence of single or multiple clinical features such as
      menstrual cycle disturbances, obesity, acne, hirsutism, alopecia and biochemical
      abnormalities such as hypersecretion of luteinising hormone and testosterone. In
      a significant number of women with this condition there is impaired insulin
      metabolism. Women with the polycystic ovary syndrome are at an increased risk of
      developing diabetes and possibly cardiovascular disease in later life. The
      management should be symptom-orientated. Menstrual cycle regulation may be
      attained with the combined oral contraceptive pill or cyclical progestogen
      therapy. In obese women, with the loss of weight, the symptoms and endocrine
      profile are generally improved. Short-term treatment with metformin may be useful
      in women with insulin resistance. Hyperandrogenism may be treated with the
      contraceptive pill containing cyproterone acetate or with short-term low-dose
      anti-androgen therapy, together with effective contraception. Ovulation may be
      induced with clomiphene citrate with careful monitoring, failing which low-dose
      gonadotrophin therapy or laparoscopic ovarian diathermy are effective options.

PMID- 17454456
TI  - The inferior hypogastric plexus: a different view.
AB  - The morphology of the inferior hypogastric plexus has been demonstrated in a
      series of dissections of nulliparous cadavers. Each cadaver was embalmed in a
      solution containing a significant proportion of methanol which preserved the
      pliability of the tissues enabling the nerve plexi to be clearly demonstrated.
      These structures are not normally encountered during general gynaecological
      surgery and clinicians are often unaware of the possible consequences of injury
      during vaginal delivery or sustained constipation. Denervation of pelvic organs,
      with subsequent reinnervation over the medium term, may account for a variety of
      obstetric and gynaecological syndromes.

PMID- 17454457
TI  - The value of highly active antiretroviral therapy in the prevention of mother-to
      child transmission of HIV.
AB  - Over 90% of the children infected with HIV globally were as a result of mother-to
      child transmission. With a high prevalence of HIV among women of reproductive age
      and a high fertility rate in Nigeria, the prevention of mother-to-child
      transmission of HIV is an important strategy to curb the menace of HIV. This
      paper examines the value of highly active antiretroviral treatment in the
      prevention of mother-to-child transmission of HIV. Pregnant women attending the
      antenatal clinic of the University of Maiduguri Teaching Hospital were offered
      voluntary counselling and testing for HIV. Seropositive women who fulfilled the
      criteria for administration of antiretroviral drugs were offered a triple
      combination of nevirapine, stavudine and lamivudine in pregnancy. Women who did
      not fulfil the criteria were offered single dose nevirapine in labour. The
      newborn of all HIV-positive women were offered nevirapine suspension within 72 h
      of delivery. Overall transmission rate for women who had combination treatment
      was 9.1% which was lowered to zero level among those that had elective caesarean
      section and infant formula in addition to the drugs. Those who had single dose
      nevirapine in labour had a transmission rate of 33.3%. It is recommended that the
      single dose nevirapine be abandoned in favour of combination treatment.

PMID- 17454458
TI  - Predicting lapse when stopping smoking among pregnant and non-pregnant women.
AB  - This study aimed to investigate factors predicting lapse among pregnant and non
      pregnant women when trying to stop smoking. A total of 40 women, pregnant and non
      pregnant, were investigated over a 2-week period when trying to stop smoking. One
      quarter of the women lapsed every day. Not being pregnant was a significant
      predictor for the occurrence of any lapse during the time period, whereas age,
      number of years of smoking, number of earlier attempts to stop smoking, and
      number of cigarettes smoked per day did not predict lapse. There was a four times
      higher risk for lapse in non-pregnant compared with pregnant women. Being
      pregnant gives an opportunity to help stop smoking with a considerably lower risk
      of lapse compared with non-pregnant women.

PMID- 17454459
TI  - Are we complying with NICE guidelines on the use of prostaglandin E2 for
      induction of labour? A survey of obstetric units in the UK.
AB  - To determine whether obstetric units in the UK comply with the recommendations by
      the National Institute for Clinical Excellence (NICE) on the maximum doses of
      intravaginal prostaglandin for induction of labour, a cross-sectional telephone
      survey of all obstetric units in the UK listed on Dr Foster's website was
      undertaken. The maximum doses recommended by NICE were exceeded by 86.4% (76/88)
      and 61.1% (55/90) of units that use intravaginal prostaglandin tablet and
      intravaginal prostaglandin gel, respectively. Units that use prostaglandin
      tablets were four times more likely to exceed the recommended maximum dose (OR =
      4.03, 95% CI, 1.9 - 8.4), six times more likely to use 50% or more of the
      recommended maximum dose for nulliparous women (OR = 5.9, 95% CI, 3.1 - 11.0),
      and six times more likely to use 50% or more of the recommended maximum dose for
      multiparous women (OR = 6.5, 95% CI, 3.0 - 13.9). A majority of obstetric units
      in the UK exceed the maximum doses of intravaginal prostaglandin recommended by
      NICE for induction of labour.

PMID- 17454460
TI  - Uptake of invasive testing following a positive triple test for Down's syndrome.
      Are midwives different counsellors compared with obstetricians?
AB  - A review of the uptake rate of diagnostic tests following a positive triple test
      was undertaken in the two maternity units of the Hull and East Yorkshire NHS
      Trust. In one unit, midwives were actively involved in counselling and in the
      other, counselling was performed by Consultant obstetricians. During the study
      period, there were 721 (7.1% positive rate) positive triple tests. Of these, 212
      (29.4%) and 509 (70.6%) were counselled by midwives and Consultant obstetricians,
      respectively. There was no significant difference in uptake of amniocenteses or
      chorionic villous sampling with respect to the counsellor with an uptake of 60.4%
      in the midwife counselled group compared with 67.6% in the Consultant counselled
      group (p = NS). We believe the determinants of the uptake rate of a diagnostic
      test are patient centred if adequate counselling is provided. Midwives will
      continue to play a role in counselling and should be encouraged to do so to
      reduce the burden on obstetricians.

PMID- 17454461
TI  - Severe pre-eclampsia and eclampsia in Abha, the south west region of Saudi
      Arabia.
AB  - A retrospective study was conducted over a 10-year period on 32,000 maternities
      at Abha General Hospital, Abha, Saudi Arabia, to estimate the contribution of
      eclampsia and severe pre-eclampsia to maternal mortality and morbidity and also
      fetal wastage. It included 18 cases of eclampsia and 297 cases of severe pre
      eclampsia. Multiple regression analysis revealed that only the presence of
      prodromal symptoms significantly affected the occurrence of eclampsia, p < 0.05,
      while nulliparous patients were a high risk group for eclampsia. Maternal
      complications including eight cases of massive ascites occurred exclusively in
      severe pre-eclamptics. Although no maternal deaths were reported, the perinatal
      mortality rate was 16.6% and 14.1% among the eclamptics and severe pre-eclamptic
      patients, mainly from prematurity. Regarding the eclamptic patients, 17(94.4%)
      had the first fit before arrival at the hospital, 13(72.2%) before labour, while
      3(16.6%) had fits before and during labour and 1(5.6%) had the fits after
      delivery. Suggestions are proffered to reducing maternal morbidity and perinatal
      mortality and morbidity.

PMID- 17454462
TI  - Pre-term labour in cases with high maternal testosterone levels.

PMID- 17454463
TI  - Preparation for induction of labour with an unfavourable cervix using a Foley's
      catheter.

PMID- 17454464
TI  - Parietal peritoneal closure at caesarean section revisited.

PMID- 17454465
TI  - Knowledge of female genital mutilation among healthcare professionals.
AB  - The World Health Organisation estimates that 2 million women undergo some form of
      female genital mutilation (FGM) annually. Because of increasing migration,
      clinicians in the UK are increasingly exposed to women who have suffered FGM.
      Recognising this trend, the RCOG has set standards for guidance of health
      professionals caring for women with FGM. As yet, no study has assessed levels of
      knowledge of FGM among relevant health professionals. An anonymous structured
      questionnaire based on the Royal College of Obstetricians and Gynaecologists'
      standards was circulated among staff at a University Teaching Hospital. A total
      of 45 participants completed the questionnaire. Only 40% were familiar with the
      regulations in the FGM Act of 2003; 58% were unable to list the different
      categories of FGM; 47% incorrectly thought that caesarean section is the best way
      of managing FGM if vaginal examination is not possible in the first stage of
      labour and 54% chose anterior episiotomy as the treatment of choice during the
      second stage. Our study found that there were significant gaps both in
      theoretical knowledge and practice.

PMID- 17454466
TI  - Could gamma/delta T cells influence the mother's rejection in recurrent aborted
      embryos?
AB  - The possibility that the investigation of aborted material may identify
      aetiologies not easily detectable from even a careful clinical investigation,
      suggested a study of the T-cell receptors (TCRs) of decidual-infiltrating T
      lymphocytes in recurrent spontaneous miscarriage (RSM). From 33 cases of RSM (>3
      previous consecutive miscarriages, range 3-5, mean 3.7), PCR products were
      analysed by 15% acrylamide gel electrophoresis and visualised under UV
      illumination after ethidium bromide staining. A broad band obtained suggests the
      presence of a monoclonal T-lymphocyte proliferation. A PCR not showing bands
      means that the tissue does not contain reactive T cells. A total of 11 samples
      (33.3%) revealed the presence of receptor TCRgamma with the presence of a
      specific band. T-cell receptors in RSM were identified in one-third of cases.
      These data underline the importance of a maternal immune host response to the
      embryo and the need to study the immune mechanisms with the hope of modulating
      therapeutic treatment of recurrent abortion.

PMID- 17454467
TI  - Randomised trial showing that lidocaine should be "squirted" through a peritoneal
      drain before it is removed.
AB  - A block randomised, non-blinded trial was performed to see if injecting lidocaine
      down a surgical drain could reduce the pain associated with its removal. A total
      of 36 women who had a closed suction intraperitoneal drain after elective
      gynaecological surgery were randomly allocated to conventional drain removal or
      drain removal 5-10 min after squirting 10 ml 2% lidocaine down the drain tube. We
      found that the pain associated with removal of the drain is variable but can be
      reduced significantly with lidocaine. The median pain score (95% range) during
      drain removal was 3.0 (2.5 - 5.0) in the group allocated lidocaine compared with
      5.5 (4.6 - 6.5) if lidocaine was not used (median difference = 2.0; 95%
      confidence interval for the difference between medians is 1 - 3.5). In summary,
      the median pain score was halved by injecting lidocaine down the drain tubing
      before removal.

PMID- 17454468
TI  - Compliance with the published RCOG guidelines in women undergoing hysterectomy
      for menorrhagia in a district general hospital.
AB  - The Royal College of Obstetricians and Gynaecologists (RCOG) published guidelines
      describing the management of menorrhagia in primary and secondary care. In this
      study, we reviewed retrospectively, the compliance with these guidelines in women
      who underwent a hysterectomy for menorrhagia over a 3-year period in a District
      General Hospital. Case notes were reviewed for 22 women in whom the uterus was
      reported normal on histology. There was a high level of compliance in clinical
      assessment before hysterectomy. Nearly 70% of women received some form of medical
      treatment, however only 50% were offered endometrial ablation. Compliance was
      high in imparting information about the risk factors of hysterectomy and in
      administering thromboprophylaxis.

PMID- 17454469
TI  - Prevalence of occult stress incontinence in continent women with severe genital
      prolapse.
AB  - We studied 32 clinically continent women with severe prolapse. We found evidence
      of occult stress incontinence in 10 of these women after reduction of the
      prolapse with a ring pessary. Our results, confirming the work of others, suggest
      that a high proportion of women with severe genito-urinary prolapse are at an
      increased risk of occult stress incontinence that could result in incontinence
      after surgery for prolapse. Urodynamic studies after restoring anatomy with a
      ring pessary may identify these women needing anti-incontinence procedures at the
      time of surgical repair of the prolapse.

PMID- 17454470
TI  - Transobturator tape procedure in stress urinary incontinence: UK experience of a
      district general hospital.
AB  - We aimed to assess the effectiveness and complications of transobturator tape
      (TOT) in the treatment of female stress urinary incontinence (SUI). This was a
      retrospective study of case notes of women who had a TOT procedure between
      December 2003 and July 2005 at a district general hospital. We reviewed 135 case
      notes on the TOT procedures performed during the study period. Mean age was 55.9
      years (range 28-93 years). The mean follow-up period was 3 months (range 6 weeks
      12 months). There were no major complications and 18 minor complications were
      noted. Six patients were lost to follow-up. In the short term, the subjective
      level of complete cure and improvement reported by patients was 89.6% and 8.8%,
      respectively. The cure rates were not related to the patient's body mass index
      (BMI), preoperative urodynamics (UDS), previous pelvic surgery, type of
      anaesthesia, concomitant pelvic surgery or occurrence of complications. TOT seems
      to be a safe and effective procedure for treating female SUI, avoiding the major
      risks of the retropubic approach. A robustly designed randomised controlled trial
      with long-term follow-up is necessary to assess long-term success rate and
      complications when compared with other procedures.

PMID- 17454471
TI  - Cervical cancer screening practices among general practitioners in Lagos Nigeria.
AB  - Cervical cancer is the most common genital cancer in women in Nigeria. We studied
      the cervical cancer screening practices of 503 general practitioners in two urban
      and two rural areas of Lagos state. Only 60 (11.9%) ever informed their patients
      about cervical cancer screening and female doctors did this more often than their
      male counterparts (chi(2) = 4.74, p = 0.001). A total of 89 (17.8%) had
      facilities for Pap smears but only 27(5.4%) screened their patients. A total of 6
      out of 27 (22.2%) did routine screening and 21 (77.8%) did selective screening.
      Only 6 out of 503 (1.2%) therefore did routine screening. Some 126 (25.0%) and
      109 (21.7%) would do Pap smears for patients with post-coital bleeding and post
      menopausal bleeding. Screening services were more available in the urban than in
      the rural areas (p = 0.0000). Thus, cervical cancer screening practices and
      services in Lagos are inadequate, which is no different from other parts of
      Nigeria and sub-Saharan Africa. Cervical cancer should be accorded the same
      attention as HIV, malaria, TB and childhood immunisations.

PMID- 17454472
TI  - Perivascular nerve fibre proliferation: the consequence of prolonged straining.
AB  - Four clinical cases are described in which a history of straining to achieve
      defaecation over many years, was associated with prolonged pelvic pain and the
      neuro-immunohistochemical observation of perivascular nerve fibre proliferation
      (PVNFP). Specimens of uterus, vagina, vulva and bladder have all demonstrated
      this novel histological feature. In three of the four cases, treatment with
      gonadotrophin releasing hormone agonists was associated with temporary
      improvement of the pain.

PMID- 17454473
TI  - The use of Monsel's solution and vaginal pack for haemostasis in cold knife cone
      biopsy.

PMID- 17454474
TI  - Vernix caseosa peritonitis: an unusual and rare complication of caesarean
      section.

PMID- 17454475
TI  - A simple surgical approach in the treatment of cervical pregnancy.

PMID- 17454476
TI  - Hemiplegic stroke following pre-eclamptic intracerebral haemorrhage: challenges
      of multidisciplinary management.

PMID- 17454477
TI  - A vesico-peritoneal fistula presenting with pain.

PMID- 17454478
TI  - Uterine artery embolisation as an interval adjunct to conservative management of
      placenta praevia increta.

PMID- 17454479
TI  - Successful myomectomy in early second trimester of pregnancy.

PMID- 17454480
TI  - Novel correction technique of chronic puerperal inversion of the uterus.

PMID- 17454481
TI  - When should a cough in pregnancy not be ignored?

PMID- 17454482
TI  - Pregnancy and mode of delivery in patients with familial polyposis.

PMID- 17454483
TI  - A case of recurrent first-trimester Fowler syndrome.

PMID- 17454484
TI  - First trimester rupture of previous caesarean section scar.

PMID- 17454485
TI  - Delayed presentation of vesicouterine fistula 12 months after uterine artery
      embolisation for uterine fibroids.

PMID- 17454486
TI  - A self attempted cutting of a uterovaginal prolapse.

PMID- 17454487
TI  - Heterotopic intrauterine bone formation.

PMID- 17454488
TI  - Transvaginal repair of post-coital rectovaginal fistula in patients of vaginal
      agenesis.

PMID- 17454489
TI  - Bowel evisceration through the vaginal vault: a delayed complication following
      hysterectomy.

PMID- 17454490
TI  - An ileal migration of a retained surgical swab (gossypiboma): a rare cause of an
      epigastric mass.

PMID- 17454491
TI  - Ruptured ectopic pregnancy concealing thyroid storm.

PMID- 17454492
TI  - Unusual presentation of uterine sarcoma.

PMID- 17454493
TI  - Fallopian tube carcinoma presenting as an endometrial polyp.

PMID- 17454494
TI  - Pelvic tuberculosis with elevated serum CA125: a diagnostic dilemma.

PMID- 17454495
TI  - Impending rupture of a uterine horn pregnancy at 19 weeks' gestation: timely
      management or near miss?

PMID- 17454497
TI  - Re: Malomo OO, Kuti O, Orji EO, Ogunniyi SO, Sule SS. A randomised controlled
      study of non-closure of peritoneum at caesarean section in a Nigerian population.
      Journal of Obstetrics and Gynaecology 2006;26:429-432.

PMID- 17454499
TI  - Worker exposure to volatile organic compounds in the vehicle repair industry.
AB  - This study evaluated exposures among vehicle repair technicians to hexane,
      acetone, toluene, and total volatile organic compounds (VOCs). On randomly
      selected workdays, we observed a characteristic pattern of solvent use among 36
      technicians employed in 10 repair shops, each of which used an aerosol solvent
      product. We obtained quantitative exposure measurements from a subset of nine
      technicians (employed in three of these shops) who used an aerosol product
      containing hexane (25-35%), acetone (45-55%), and toluene (5-10%). The time
      weighted average (TWA) exposure concentration for task-length breathing zone (BZ)
      samples (n = 23) was 36 mg/m(3) for hexane, 50 mg/m(3) for acetone, and 10
      mg/m(3) for toluene. The TWA area concentrations (n = 49) obtained
      contemporaneously with BZ samples ranged from 25% to 35% of the BZ
      concentrations. The solvent emission rate (grams emitted/task time) was
      correlated with the total VOC exposure concentration (R(2) = 0.45). The
      proportions of VOCs in the BZ samples were highly correlated (r = 0.89 to 0.95)
      and were similar to those of the bulk product. Continuous exposure measurements
      for total VOCs (n = 1238) during 26 tasks produced a mean BZ VOC "pulse" of 394
      mg/m(3) within 1 min following initiation of solvent spraying. The geometric mean
      air speed was 5.2 meters/min in the work areas (n = 870) and was associated with
      0.8 air changes per minute in the BZ. The findings suggest that vehicle repair
      technicians who use aerosol solvent products experience episodic, inhalation
      exposures to the VOCs contained in these products, and the proportions of VOCs in
      the breathing zone are similar to those of the bulk product. Because acetone
      appears to amplify the severity and duration of the neurotoxic effects of n
      hexane, products formulated with both hexane and acetone should be avoided.
      Further evaluation of exposures to VOCs is needed in this industry, along with
      information on effective alternatives to aerosol solvent products.

PMID- 17454500
TI  - Glutaraldehyde exposures among workers making bioprosthetic heart valves.
AB  - Exposure to glutaraldehyde is a recognized cause of work-related asthma. An
      investigation was undertaken to describe exposure to glutaraldehyde among workers
      making bioprosthetic heart valves and to make recommendations for prevention. At
      the two largest heart valve manufacturing facilities in California, the work
      process was observed; employer representatives and glutaraldehyde-exposed workers
      were interviewed; and employer written records, including company-generated
      industrial hygiene data, were analyzed. Approximately 600 female workers had
      continuous airborne exposure to glutaraldehyde over the course of every work
      shift and the routine potential for skin and eye contact with glutaraldehyde
      while making heart valves. Employee short-term (15-min) glutaraldehyde exposures
      were all well below the current regulatory ceiling level (0.20 ppm). Overall,
      approximately 40% of the glutaraldehyde-related job tasks involved exposures
      above the American Conference of Industrial Hygienists threshold limit value
      ceiling of 0.05 ppm; the majority (71.4% and 83.3%, depending on the company)
      involved exposures greater than 0.015 ppm. At one company, two cases of physician
      diagnosed asthma were recorded by the employer in the previous 5-year period;
      these reports met the surveillance case definition for new-onset, work-related
      asthma associated with a known asthma inducer. Factors that contributed to worker
      exposure included large exposed surface areas of glutaraldehyde under agitation;
      working with glutaraldehyde-treated tissue in proximity to workers' breathing
      zones; manual pouring and disposal of glutaraldehyde solutions without local
      exhaust ventilation, eye protection, and waste neutralization; and prolonged use
      of latex gloves. Workers making bioprosthetic heart valves are at risk for
      occupationally acquired asthma. Employers should implement additional engineering
      controls to minimize workers' exposures to at least below a level of 0.015 ppm,
      an appropriate glove to prevent workers' skin exposure to glutaraldehyde,
      consistent and universal use of eye protection, and a medical surveillance
      program for glutaraldehyde-exposed workers.

PMID- 17454501
TI  - Hand-handle interface force and torque measurement system for pneumatic assembly
      tool operations: suggested enhancement to ISO 6544.
AB  - A hand-handle interface force and torque measurement system is introduced to fill
      the void acknowledged in the international standard ISO 6544, which governs
      pneumatic, assembly tool reaction torque and force measurement. This system
      consists of an instrumented handle with a sensor capable of measuring grip force
      and reaction hand moment when threaded, fastener-driving tools are used by
      operators. The handle is rigidly affixed to the tool in parallel to the original
      tool handle allowing normal fastener-driving operations with minimal
      interference. Demonstration of this proposed system was made with tools of three
      different shapes: pistol grip, right angle, and in-line. During tool torque
      buildup, the proposed system measured operators exerting greater grip force on
      the soft joint than on the hard joint. The system also demonstrated that the soft
      joint demanded greater hand moment impulse than the hard joint. The results
      demonstrate that the measurement system can provide supplemental data useful in
      exposure assessment with power hand tools as proposed in ISO 6544.

PMID- 17454502
TI  - Characterization and mapping of very fine particles in an engine machining and
      assembly facility.
AB  - Very fine particle number and mass concentrations were mapped in an engine
      machining and assembly facility in the winter and summer. A condensation particle
      counter (CPC) was used to measure particle number concentrations in the 0.01
      microm to 1 microm range, and an optical particle counter (OPC) was used to
      measure particle number concentrations in 15 channels between 0.3 microm and 20
      microm. The OPC measurements were used to estimate the respirable mass
      concentration. Very fine particle number concentrations were estimated by
      subtracting the OPC particle number concentrations from 0.3 microm to 1 microm
      from the CPC number concentrations. At specific locations during the summer
      visit, an electrical low pressure impactor was used to measure particle size
      distribution from 0.07 microm to 10 microm in 12 channels. The geometric mean
      ratio of respirable mass concentration estimated from the OPC to the
      gravimetrically measured mass concentration was 0.66 with a geometric standard
      deviation of 1.5. Very fine particle number concentrations in winter were
      substantially greater where direct-fire natural gas heaters were operated (7.5 x
      10(5) particles/cm(3)) than where steam was used for heat (3 x 10(5)
      particles/cm(3)). During summer when heaters were off, the very fine particle
      number concentrations were below 10(5) particles/cm(3), regardless of location.
      Elevated very fine particle number concentrations were associated with machining
      operations with poor enclosures. Whereas respirable mass concentrations did not
      vary noticeably with season, they were greater in areas with poorly fitting
      enclosures (0.12 mg/m(3)) than in areas where state-of-the-art enclosures were
      used (0.03 mg/m(3)). These differences were attributed to metalworking fluid mist
      that escaped from poorly fitting enclosures. Particles generated from direct-fire
      natural gas heater operation were very small, with a number size distribution
      modal diameter of less than 0.023 microm. Aerosols generated by machining
      operations had number size distributions modes in the 0.023 microm to 0.1 microm
      range. However, multiple modes in the mass size distributions estimated from OPC
      measurements occurred in the 2-20 microm range. Although elevated, very fine
      particle concentrations and respirable mass concentrations were both associated
      with poorly enclosed machining operations; the operation of the direct-fire
      natural gas heaters resulted in the greatest very fine particle concentrations
      without elevating the respirable mass concentration. These results suggest that
      respirable mass concentration may not be an adequate indicator for very fine
      particle exposure.

PMID- 17454503
TI  - Fundamental factors affecting upper-room ultraviolet germicidal irradiation -
      part II. Predicting effectiveness.
AB  - Compared with increasing outdoor air ventilation rate, upper-room ultraviolet
      germicidal irradiation (UVGI) is an attractive technology for lowering the indoor
      concentration of airborne microorganisms and thereby reducing the risk of
      airborne transmission of disease. With relatively modest vertical air
      circulation, most of the air in a room can be irradiated in a relatively brief
      time period without noise or significant power consumption. The hypothesis tested
      in this study is that the efficacy of upper-room UVGI to inactivate or kill
      airborne infectious microorganisms can be determined from an index of UVGI
      effectiveness, a dimensionless parameter designed to characterize adequacy of
      vertical air circulation, amount of UVGI provided, and their interaction. This
      index of effectiveness, which is determined independently of microbiological
      testing, was found to correlate well with experimental measurements made in a
      room-size chamber. A comparison of two other dimensionless parameters - the
      irradiation number and mixing number, from which effectiveness index is
      calculated - provides insight into whether the quantity of UV provided to the
      upper room or the intensity of the vertical air circulation is the controlling
      factor for effective application of upper-room UVGI. The irradiation number is
      calculated from the UV power output of the fixture(s), a parameter that is
      fixture specific and much easier to measure than mean fluence rate. An equation
      was also developed that relates UV fixture power output to mean fluence rate in
      either the irradiated zone or the entire room. In addition, reductions in viable
      microorganism concentration due to UVGI predicted from a two-box model are
      compared with experimental measurements.

PMID- 17454504
TI  - Estimating service lives of organic vapor cartridges III: multiple vapors at all
      humidities.
AB  - A published model for estimating service lives of organic vapor (OV) air
      purifying respirator cartridges has been extended to include multiple organic
      vapors at all humidities. Equilibria among the OVs are calculated using Ideal
      Adsorbed Solution Theory, whereas the effects of adsorbed water are considered as
      due to micropore volume exclusion. Solubilities of OVs in water must also be
      taken into account. Adsorption kinetics of components of mixtures are based on
      published correlations of the effects of covapors and water vapor. The dynamics
      of adsorption and competition are incorporated using expanding zones within the
      carbon bed, taking into account vapor and water displacements. Measurements of
      breakthrough curves for two ternary OV mixtures at high humidities have been done
      for a single cartridge type. The service life estimation model, implemented as a
      spreadsheet and a computer program, has been tested against these data as well as
      data for OV mixtures from literature sources. Good agreements were obtained
      between model predictions and experimental breakthrough times at dry conditions
      and humid conditions.

PMID- 17454505
TI  - Uses of and exposure to trichloroethylene in U.S. industry: a systematic
      literature review.
AB  - This article describes a systematic review of the industrial hygiene literature
      for uses of trichloroethylene (TCE) in industry for the exposure assessment of
      two population-based case control studies of brain cancer in the United States.
      Papers and reports that address uses of and exposures to TCE were identified from
      MEDLINE, TOXLINE, NIOSHTIC, the NIOSH Health Hazard Evaluation database
      (keywords: chlorinated solvents and trichloroethylene), and in other reviews.
      This search was complemented by reviewing the reference lists from the identified
      literature. The collected information was systematized by the Standard Industrial
      Classification (SIC) system, and measurement data reported in the literature were
      summarized in a database. TCE use was extensive from the early 1920s through the
      1970s mainly as a degreasing agent in metal-fabricating operations. After the
      1970s it became less popular because of environmental concerns. TCE historically
      has had a multitude of uses in many other industries, e.g., dry cleaning,
      textile, electronics, leather, and rubber. Also, many products like adhesives,
      drugs, paints, inks, and various industrial products have contained TCE. It was
      banned as a food additive and in cosmetics in 1977. The arithmetic mean (AM) of
      the measurements across all industries and decades was 38.2 ppm. The highest
      personal and area air levels were reported in vapor degreasing (AM of 44.6 ppm).
      Most TCE measurements were performed in the 1950s, 1970s, and 1980s. The data
      described here could be used by exposure assessors as is to identify the presence
      and approximate levels of exposure. Using the same information as a basis should
      increase the reliability of the assessments, making it easier to compare both the
      exposure assessment methods and the epidemiologic results across different
      studies.

PMID- 17454506
TI  - Wet abrasive blasting with a win nozzle--a case study.

PMID- 17454507
TI  - Quality of dying.

PMID- 17454508
TI  - Psychological mood state of opiate addicted women during pregnancy and postpartum
      in comparison to non-addicted healthy women.
AB  - Opiate addiction has been widely documented to have a negative impact on
      pregnancy course and outcome. The unfavorable psychosocial situation of addicted
      women predispose for poor processing of the physiological and psychological
      demands of pregnancy. Thus the aim of our study was to investigate the
      psychological mood state of opiate addicts during pregnancy and postpartum in
      comparison to healthy women. In a case-controlled, prospective, longitudinal
      study, nine pregnant opiate addicts and nine healthy pregnant women matched by
      age, level of education and gestational age at birth were interviewed in the
      third trimester of pregnancy and postpartum. Standardized questionnaires and
      inventories for assessment of the general psychopathology and emotional state,
      the perceived self-efficacy expectancy, the psychosocial adaptation to pregnancy
      and the fear of delivery, respectively were applied. Addicted women achieved
      significantly higher scores in the test assessing general psychopathology and
      emotional state before delivery compared to abstinent women. Interestingly this
      difference was unverifiable postpartum. This study reaffirms the presumption of a
      disadvantageous psychological condition in pregnant opiate addicts in comparison
      to healthy pregnant women for the first time in a prospective case-control study
      design.

PMID- 17454509
TI  - The first pelvic examination.
AB  - PURPOSE: To describe adolescents' experiences of their first pelvic examination.
      METHODS: Data were collected by tape-recorded interviews with 15 adolescents, who
      had had their first pelvic examination (PE) performed by a midwife at a Youth
      Clinic. Data were analyzed by qualitative latent content analysis. RESULTS: The
      result is presented in terms of the themes: Emotional ambivalence, Being in
      control and A step into women's world. The adolescents generally believed that PE
      was beneficial to their health and they were curious to see how they would
      manage. On the other hand they also felt embarrassed about getting undressed.
      They described several factors which contributed to feelings of being in control
      of the situation, e.g., when the examiner shared the process of decision making,
      thoroughly explained the PE procedure in advance, and assured them that the PE
      could be discontinued at any time. They considered their first PE as a step into
      a women's world. It seems important that the examiners perform the first PE in a
      manner that empowers the adolescents so they can enter womanhood with a positive
      attitude to their bodies. Furthermore, this empowering process may lay the
      foundation for subsequent PEs to be educational events for the adolescents.

PMID- 17454510
TI  - Contraceptive counseling by gynecologists--which issues are discussed and does
      gender play a role?
AB  - OBJECTIVES: Explorative pilot study with the aim of gaining insight into the
      contraceptive counseling practices and possible gender differences of a selected
      group of male and female gynecologists. DESIGN: Semi-structured telephone
      interviews of 48 gynecologists concerning the content and strategies of their
      contraceptive counseling with special focus on aspects relevant to patient
      adherence. RESULTS: Male and female gynecologists inform equally frequently about
      various methods and reproductive health aspects such as risks, the advantages and
      disadvantages of the methods and side effects. Male physicians speak more often
      about the efficiency and benefits of the methods, while their female colleagues
      emphasize STI and emergency contraception. Sexual health aspects were seldom
      mentioned as issues of discussion. For the choice of a contraceptive method
      efficiency was considered very important by 100%, reversibility by 83%, side
      effects by 85% and convenience by 79%. Naturalness and costs were more often
      quoted as important by female, and benefits by male gynecologists. Side effects
      are considered the most important factor for patient adherence by 60%, counseling
      and information is predominantly cited by female, and patient's character and
      personality by male doctors. CONCLUSIONS: While contraceptive counseling by
      practising gynecologists includes basic information about available methods and
      their efficiency, as well as some reproductive health issues, sexual health
      issues are often neglected. Gender differences occasionally influence the choice
      of the topics as well as the attitude towards the patient.

PMID- 17454511
TI  - A model for critical review of literature - with vaginismus as an example.
AB  - In this article we present a behavioral model for the critical review of the
      literature within a certain research field, using vaginismus as an example. We
      searched the literature for the title word "vaginismus" and analyzed to what
      extent the articles dealt with the following seven categories: prevention,
      etiology, maintaining factors, consequences, object of intervention, method of
      intervention, and method of evaluation. In each category we scrutinized the
      content of the articles for biological, psychological, social, relational, and
      gender aspects. Quality requirements of etiological and treatment studies were
      then added and the results presented in a "quality-adjusted" model. There were
      102 articles during 1985-2001, of which 22 were included in the review. Most of
      the articles deal with supposed predisposing factors of etiology and different
      aspects of intervention. Only a few articles discuss precipitating factors,
      maintaining factors, or consequences of the problem. No article had a gender
      analysis. Only 11 of the articles fulfilled some of the proposed quality
      criteria. We found the behavioral model with quality requirements useful for
      classifying and evaluating the literature of vaginismus. The model may also be
      used as a guide to design methodologically good studies.

PMID- 17454512
TI  - Pregnancy interrupted: loss of a desired pregnancy after diagnosis of fetal
      anomaly.
AB  - Prenatal diagnostic techniques both enable and force women and couples to make
      decisions about whether to continue a pregnancy where the fetus has an anomaly.
      Few studies have explored the decision-making and bereavement processes of women
      who terminate a desired pregnancy after the discovery of a fetal anomaly. This
      reports the qualitative results of a study designed to explore these processes
      while placing them within the context of the societal milieu. Findings are
      reported as themes that emerged from the 30 intensive interviews conducted with
      women at varying stages after this experience. These include mythical
      expectations based on denial that anomaly could occur, misconceptions about the
      nature of prenatal testing and inaccurate expectations about the experience and
      duration of grief. Further, the contradictory norms in society are defined as
      creating additional dilemmas for women as they attempt to gain support and
      understanding following their loss. Suggestions for how providers may assist
      women with their grief are incorporated.

PMID- 17454513
TI  - Impact of education on women with perinatal depression.
AB  - OBJECTIVE: To assess the impact that education through participation in a
      depression screening program has on mental health literacy and help seeking
      behavior in perinatal women. METHODS: Responses to a hypothetical case of
      depression, help seeking behavior, and screening levels for risk of depression
      using the Edinburgh Postnatal Depression Scale were compared between two groups
      of postnatal women; one group who had participated in a screening program and the
      other who had not. Those who participated in the screening program were also
      asked to evaluate the educational material they had received. RESULTS: A total of
      1309 women, broadly representative of postnatal women, answered one or more
      questionnaires. Those who had participated in the screening program were better
      able to recognize depression in a hypothetical case, and also assess their own
      mental state more appropriately. Those women who had been part of the program and
      did not score high on the EPDS were less likely to seek help, were more satisfied
      when they did and tended to benefit more from the educational booklet.
      CONCLUSIONS: Participation in a screening program with educational material had
      significant benefits for mental health literacy and the health service use for
      perinatal women at risk for depression.

PMID- 17454514
TI  - Maternal distress and intended breastfeeding duration.
AB  - AIM: To evaluate the associations between maternal psychological status and
      intended breastfeeding duration. METHODS: A total of 852 pregnant women who
      attended antenatal care between September 1997 and August 2000 in 12 health units
      and five hospitals in Jundiai city, Brazil, were included in the study.
      Psychological measures (stress and distress) were obtained at a gestational age
      from 30 to 36 weeks, using standardized scales, questionnaires and inventories.
      Psychological factors specifically related to breastfeeding assessed their
      worries, concerns, and support when breastfeeding. Multiple linear regression
      analysis identified the associations between the outcome "intended duration of
      breastfeeding" and psychological status of the mothers, controlling for toxic
      exposure, socioeconomic, demographic, obstetric and nutritional factors. RESULTS:
      There were negative associations between the outcome and distress, "concerned
      about body's changes", and work outside home, and a positive association between
      the outcome and marital status (p < or = 0.03). CONCLUSION: Early identification
      of distress in pregnant women and a more attentive encouragement to breastfeed is
      probably one of the steps to improve intended breastfeeding duration.

PMID- 17454517
TI  - Effects of completing sexual questionnaires in males and females with histories
      of childhood sexual abuse: implications for institutional review boards.
AB  - Few studies have sought to examine empirically the immediate effects of
      participation in sexual abuse research. The present study investigated the
      effects of childhood sexual abuse on measures of personality and psychological
      functioning in 250 males and females. The null hypothesis was that sexually
      abused and nonabused groups would show no significant differences between pre-and
      post-testing on measures of state anxiety, state depression, and state anger. No
      significant differences between pre-and post-testing were observed between
      nonabused, abused, and severely abused participants. In addition, there were no
      gender differences among the groups. Findings from this study support those of
      Savell, Kinder, and Young (2006) and have significant implications for
      Institutional Review Boards (IRB) as they suggest that participation in childhood
      sexual abuse or sexuality research does not place sexually abused individuals at
      greater than minimal risk for immediate increases in anxiety, depression, or
      anger.

PMID- 17454518
TI  - The relationship between serum prolactin level and sexual functioning among male
      outpatients with schizophrenia or schizoaffective disorder: a randomized double
      blind trial of risperidone vs. quetiapine.
AB  - Examine the relationship between serum prolactin level and sexual functioning
      among male outpatients with schizophrenia or schizoaffective disorder who were
      treated with risperidone or quetiapine. Male outpatients (N = 22, age > or = 18
      years) with schizophrenia or schizoaffective disorder who had experienced
      risperidone-associated sexual dysfunction prior to the study were randomized to 6
      weeks of double-blind risperidone continuation (mean dose = 4.3 mg/day, SD = 1.2)
      or quetiapine switch (mean dose = 300 mg/day, SD = 66.7) treatment. Serum
      prolactin levels at baseline and at the end of week 6 (final visit) were
      obtained. The five-item Arizona Sexual Experience Scale (ASEX) assessed sexual
      functioning at baseline and at week 6. A mixed linear model analysis of
      covariance, with baseline ASEX and Positive and Negative Syndrome Scale (PANSS)
      scores as covariates, was used to examine the relationship between serum
      prolactin level (at week 6) and sexual functioning (at week 6). The raw
      (unadjusted) Spearman rank-order correlations (r(s)) were also used to assess the
      linear association between serum prolactin level and sexual functioning. For the
      risperidone treated group (n = 12), there was a significant positive relationship
      between serum prolactin level and ASEX total score (r(s) = 0.689, beta = 0.17, p
      = .04) and three of the five ASEX subitems (ASEX subitem 1, strength of sex
      drive, beta = 0.03, p = .04; ASEX subitem 2, sexual arousal, beta = 0.04, p =
      .04; and ASEX subitem 3, penile erection, beta = 0.04, p = .02). There was no
      significant relationship, for the quetiapine group (n = 10), between serum
      prolactin level and ASEX total score (p = .55) and any of the ASEX subitems (p's
      > .20). In this 6-week randomized double-blind trial, higher serum prolactin
      level was related to greater impairment of sexual functioning in male outpatients
      who were treated with risperidone, but not with quetiapine.

PMID- 17454519
TI  - The female sexual function index: a methodological critique and suggestions for
      improvement.
AB  - The Female Sexual Function Index (FSFI) is a very well-worded sexual function
      screen with excellent psychometric qualities. However, some aspects of the
      scoring procedures pose conceptual and statistical problems, which we illustrate
      in part by way of an empirical example. The recommended solutions should further
      strengthen the utility and validity of this instrument.

PMID- 17454520
TI  - Trazodone and ejaculatory inhibition.
AB  - Sexual adverse effects are common with psychotropics. Rational polypharmacy may
      confound etiology. This case report describes development of ejaculatory
      inhibition in a male patient with co-morbid psychiatric diagnoses treated with
      fluoxetine, divalproex sodium, lamotrigine, trazodone, and clonazepam. Detailed
      psychotropic history with time-line of adverse effect onset implicated trazodone.
      Within 48 hours of trazodone discontinuation, ejaculatory inhibition was
      resolved. Clinicians should be aware that trazodone may cause ejaculatory
      inhibition, understand that determination of sexual adverse effects necessitates
      directed and periodic questioning as these symptoms may increase in severity over
      time, and appreciate that religious patients may find discussing this issue
      difficult.

PMID- 17454521
TI  - Sexual functioning and partner relationships in women with turner syndrome: some
      empirical data and theoretical considerations regarding sexual desire.
AB  - The aim of this study was to describe marital status, sexual history, and sexual
      functioning in a group of women with Turner syndrome, and to compare the results
      with general Swedish population data. The sample consists of 57 women over 18
      years of age. Data were collected from an interview, and using two self-report
      questionnaires: the McCoy Sexual Rating Scale and the Relationship Rating Scale
      (RS). Compared to population data, the women with Turner syndrome were less
      likely to have a partner and had had their sexual debut later. Single women
      differed more from the general population than did women with a partner,
      regarding sexual desire and sexual activity. Several women with a partner
      reported sexual problems, but unanimously reported being satisfied with their sex
      life and partner relationship. The level of sexual desire in women with Turner
      syndrome is discussed in relation to Levine's model of human sexual desire, where
      psychological and social motivational factors are considered in addition to a
      biologically based sexual drive (Levine, 1992).

PMID- 17454522
TI  - Vaginal laceration and hemorrhagic shock during consensual sexual intercourse.
AB  - Coital injury causing severe vaginal laceration is not uncommon during first
      coitus. However, hemorrhagic shock during consensual sexual intercourse is quite
      rare. In this report, there was one 30-year-old, 20-year-old one, and one 24 year
      old women who suffered severe vaginal laceration and bleeding during the process
      of consensual coitarche. All subjects were transferred to the hospital in the
      condition of impending shock. We found that the lacerated sites were located at
      right posterior fornices in all cases. We postulate that these vulnerable sites
      of vaginal laceration may be due to the dextro-rotation characteristics of the
      uterus and the distensibility of the vagina in this area. The vaginal fornix can
      be extremely distended during sexual intercourse, making it vulnerable to
      laceration in this area. Besides, there was a disproportionate genital size in
      all three cases which may be a cause of vaginal laceration. It is critical that
      such patients receive a prompt diagnosis to provide efficient management. It
      needs only simple surgical skills to cure the injury if the vital signs are
      stable. However, those survivors may need further psychological consultation to
      prevent negative impact on their future sexual functioning.

PMID- 17454523
TI  - Prevalence and psychosocial factors associated with being bothered by
      nonavailability of sexual partners among Hong Kong Chinese: a population-based
      study.
AB  - This study investigated the prevalence of being bothered by sexual-partner non
      availability (SPNA), associated risk factors, and associations with mental health
      and sexual satisfaction using a computer-assisted telephone survey. A random
      sample of 3257 and 1568 Chinese male and female respondents (aged 18-59) were
      interviewed. Sexual partner non-availability was highest in the male
      nonmarried/noncohabitating group, (18.6%) and the prevalence ranged from 1.4% to
      7.9% for other age-sex subgroups. Younger age and male gender were associated
      with SPNA. Being bothered by SPNA was significantly associated with mental health
      and vitality quality of life, general life satisfaction, and sexual satisfaction
      (OR = 1.41 to 5.21).

PMID- 17454527
TI  - Ethical issues when submitting to the Journal of Sports Sciences.

PMID- 17454528
TI  - Effects of rest interval during high-repetition resistance training on strength,
      aerobic fitness, and repeated-sprint ability.
AB  - The effect of altering the rest period on adaptations to high-repetition
      resistance training is not well known. Eighteen active females were matched
      according to leg strength and repeated-sprint ability and randomly allocated to
      one of two groups. One group performed resistance training with 20-s rest
      intervals between sets, while the other group employed 80-s rest intervals
      between sets. Both groups performed the same total training volume and load. Each
      group trained 3 days a week for 5 weeks [15- to 20-repetition maximum (RM), 2 - 5
      sets]. Repeated-sprint ability (5x6-s maximal cycle sprints), 3-RM leg press
      strength, and anthropometry were determined before and after each training
      programme. There was a greater improvement in repeated-sprint ability after
      training with 20-s rest intervals (12.5%) than after training with 80-s rest
      intervals (5.4%) (P = 0.030). In contrast, there were greater improvements in
      strength after training with 80-s rest intervals (45.9%) than after training with
      20-s rest intervals (19.6%) (P = 0.010). There were no changes in anthropometry
      for either group following training. These results suggest that when training
      volume and load are matched, despite a smaller increase in strength, 5 weeks of
      training with short rest periods results in greater improvements in repeated
      sprint ability than the same training with long rest periods.

PMID- 17454529
TI  - A modified TRIMP to quantify the in-season training load of team sport players.
AB  - The aims of the study were to modify the training impulse (TRIMP) method of
      quantifying training load for use with intermittent team sports, and to examine
      the relationship between this modified TRIMP (TRIMP(MOD)) and changes in the
      physiological profile of team sport players during a competitive season. Eight
      male field hockey players, participating in the English Premier Division, took
      part in the study (mean+/-s: age 26+/-4 years, body mass 80.8+/-5.2 kg, stature
      1.82+/-0.04 m). Participants performed three treadmill exercise tests at the
      start of the competitive season and mid-season: a submaximal test to establish
      the treadmill speed at a blood lactate concentration of 4 mmol . l(-1); a maximal
      incremental test to determine maximal oxygen uptake ([V]O(2max)) and peak running
      speed; and an all-out constant-load test to determine time to exhaustion. Heart
      rate was recorded during all training sessions and match-play, from which
      TRIMP(MOD) was calculated. Mean weekly TRIMP(MOD) was correlated with the change
      in [V]O(2max) and treadmill speed at a blood lactate concentration of 4 mmol x l(
      1) from the start of to mid-season (P<0.05). The results suggest that TRIMP(MOD)
      is a means of quantifying training load in team sports and can be used to
      prescribe training for the maintenance or improvement of aerobic fitness during
      the competitive season.

PMID- 17454530
TI  - A single session of treadmill running has no effect on plasma total ghrelin
      concentrations.
AB  - Ghrelin is a hormone that stimulates hunger. Intense exercise has been shown to
      temporarily suppress hunger after exercise. In the present study, we investigated
      whether post-exercise hunger suppression is mediated by reduced plasma total
      ghrelin concentrations. Nine men and nine women participated in the study. Their
      mean physical characteristics were as follows: age 24.8 (s(x) = 0.9) years, body
      mass index 22.9 (s(x) = 0.6) kg x m(-2), maximal oxygen uptake (VO(2max)) 57.7
      (s(x) = 2.2) ml x kg(-1) x min(-1). The participants completed two 3-h trials
      (exercise and control) on separate days in a randomized balanced design after
      overnight fasts. The exercise trial involved a 1-h treadmill run at 73.5% of
      VO(2max) followed by 2 h of rest. The control trial consisted of 3 h of rest.
      Blood samples were collected at 0, 0.5, 1, 1.5, 2, and 3 h. Total ghrelin
      concentrations were determined from plasma. Hunger was assessed following blood
      sampling using a 15-point scale. The data were analysed using repeated-measures
      analysis of variance. Hunger scores were lower in the exercise trial than in the
      control trial (trial, P = 0.009; time, P < 0.001; trial x time, P < 0.001).
      Plasma total ghrelin concentrations did not differ between trials. These findings
      indicate that treadmill running suppresses hunger but this effect is not mediated
      by changes in plasma total ghrelin concentration.

PMID- 17454531
TI  - A fluid dynamic investigation of the Big Blade and Macon oar blade designs in
      rowing propulsion.
AB  - The purpose of this investigation was to examine the fluid dynamic
      characteristics of the two most commonly used oar blades: the Big Blade and the
      Macon. Scaled models of each blade, as well as a flat Big Blade, were tested in a
      water flume using a quasi-static method similar to that used in swimming and
      kayaking research. Measurement of the normal and tangential blade forces enabled
      lift and drag forces generated by the oar blades to be calculated over the full
      range of sweep angles observed during a rowing stroke. Lift and drag force
      coefficients were then calculated and compared between blades. The results showed
      that the Big Blade and Macon oar blades exhibited very similar characteristics.
      Hydraulic blade efficiency was not therefore found to be the reason for claims
      that the Big Blade could elicit a 2% improvement in performance over the Macon.
      The Big Blade was also shown to have similar characteristics to the flat plate
      when the angle of attack was below 90 degrees , despite significant increases in
      the lift coefficient when the angle of attack increased above 90 degrees . This
      result suggests that the Big Blade design may not be completely optimized over
      the whole stroke.

PMID- 17454532
TI  - Comparisons of physical characteristics and performances among female collegiate
      rowers.
AB  - The physical characteristics and performances of female collegiate rowers were
      examined from two perspectives: level (novice, varsity) and years of
      participation (0, 1, 2, 3) in collegiate rowing. The participants were 90 female
      collegiate rowers from three US Division I university teams, of the National
      Collegiate Athletic Association (NCAA). Height, body mass, sitting height, arm
      span, skinfolds, limb circumferences, and skeletal breadths were measured. Leg
      length was estimated and Heath-Carter anthropometric somatotypes were calculated.
      Performance measures included lower-back flexibility, vertical jump, and 2-km
      time on a rowing ergometer. Descriptive statistics were calculated for the total
      sample and by level and years of experience. Multivariate analysis of variance
      and a Bonferroni-adjusted alpha level (P < 0.05) were used to test differences.
      Varsity rowers had significantly more rowing experience ( approximately 0.5
      years) before college, higher vertical jumps ( approximately 3 cm), faster 2-km
      times ( approximately 25 s), and lower endomorphic characteristics than novice
      rowers. Anthropometric and performance differences among rowers by years of
      experience were negligible with the exception of slower 2-km times (
      approximately 32 s) in rowers with no collegiate experience than rowers with
      collegiate experience. In conclusion, collegiate rowers differ to some extent in
      physical and performance characteristics by level and experience.

PMID- 17454533
TI  - Factors influencing physiological responses to small-sided soccer games.
AB  - The aim of this study was to examine the effects of exercise type, field
      dimensions, and coach encouragement on the intensity and reproducibility of small
      sided games. Data were collected on 20 amateur soccer players (body mass 73.1 +/-
      8.6 kg, stature 1.79 +/- 0.05 m, age 24.5 +/- 4.1 years, VO(2max) 56.3 +/- 4.8 ml
      x kg(-1) x min(-1)). Aerobic interval training was performed during three-, four
      , five- and six-a-side games on three differently sized pitches, with and without
      coach encouragement. Heart rate, rating of perceived exertion (RPE) on the CR10
      scale, and blood lactate concentration were measured. Main effects were found for
      exercise type, field dimensions, and coach encouragement (P < 0.05), but there
      were no interactions between any of the variables (P > 0.15). During a six-a-side
      game on a small pitch without coach encouragement, exercise intensity was 84 +/-
      5% of maximal heart rate, blood lactate concentration was 3.4 +/- 1.0 mmol x l(
      1), and the RPE was 4.8. During a three-a-side game on a larger pitch with coach
      encouragement, exercise intensity was 91 +/- 2% of maximal heart rate, blood
      lactate concentration was 6.5 +/- 1.5 mmol x l(-1), and the RPE was 7.2. Typical
      error expressed as a coefficient of variation ranged from 2.0 to 5.4% for percent
      maximal heart rate, from 10.4 to 43.7% for blood lactate concentration, and from
      5.5 to 31.9% for RPE. The results demonstrate that exercise intensity during
      small-sided soccer games can be manipulated by varying the exercise type, the
      field dimensions, and whether there is any coach encouragement. By using
      different combinations of these factors, coaches can modulate exercise intensity
      within the high-intensity zone and control the aerobic training stimulus.

PMID- 17454534
TI  - The importance of the International Tennis Federation's junior boys' circuit in
      the development of professional tennis players.
AB  - The relationship between junior boys' tennis success, as measured by a top 20
      International Tennis Federation's Junior Circuit (ITFJC) ranking, and subsequent
      ranking accomplishments in professional men's tennis is discussed. The names,
      countries, and birthdates of all players to achieve a top 20 ITFJC boys' year-end
      ranking from 1992 to 1998 were recorded. The progress of these players through
      the professional ranks was then tracked to the end of 2004. Results indicate that
      91% of top 20-ranked boys achieved a professional men's ranking, while a stepwise
      regression analysis revealed junior ranking (JR) to be a predictor of future,
      professional ranking (beta = 0.232, r(2) = 0.054, p < 0.05). A regression
      equation [predicted professional rank = 78.17 + 6.31*(JR)] accounted for a
      significant amount of variance in professional ranking. For male players,
      therefore, the achievement of a top 20 junior ranking appears to be a reasonable
      yardstick for future, professional success. The type of surface upon which junior
      players develop their games was also shown to influence professional ranking
      highs, with play on clay courts or a combination of clay and hard courts helping
      to produce higher, professionally ranked players than hard court play alone (p<
      or = 0.01).

PMID- 17454535
TI  - Somersaulting techniques used in high-scoring and low-scoring Roche vaults
      performed by male Olympic gymnasts.
AB  - The aim of this study was to compare the somersaulting techniques used in the 16
      highest-scoring and 16 lowest-scoring Roche vaults. Our hypothesis was that the
      gymnasts performing the highest-scoring Roche vaults would demonstrate a better
      technique than those performing the lowest-scoring Roche vaults while on the
      horse (pushing off the horse more effectively), somersaulting (executing most of
      the required somersaults higher in flight), and landing (showing a greater
      control). A 16-mm motion picture camera, operating at 100 Hz, recorded the vaults
      during the official competition. The two-dimensional direct linear transformation
      was used for spatial reconstruction. The results of t-tests (P < 0.05) indicated
      that, compared with the low-scoring gymnasts, the high-scoring gymnasts had: (1)
      greater height of body centre of mass and a more fully extended body position at
      the horse take-off; (2) greater height of body centre of mass at the peak of post
      flight, knee release, and touchdown on the mat; (3) greater horizontal and
      vertical displacements of body centre of mass, greater somersaulting rotation,
      and longer time from the knee release to mat touchdown; and (d) markedly smaller
      landing point deductions. In conclusion, a successful Roche vault is likely when
      the focus is on: (a) leaving the horse with a large vertical velocity in an
      extended body position to achieve a high trajectory of centre of mass by first
      extending the legs, then immediately pushing off the horse vigorously, using the
      muscles of the upper extremity; (b) grasping the knees immediately after the take
      off from the horse, achieving the tightly tucked body position early during the
      ascent to the peak, and completing two-thirds of the required somersaults at a
      great height; (c) releasing the knees and extending the body above the top level
      of the horse; and (d) contacting the mat with a high body centre of mass
      position.

PMID- 17454536
TI  - Acute effects of static stretching on characteristics of the isokinetic angle -
      torque relationship, surface electromyography, and mechanomyography.
AB  - The aims of this study were to examine the acute effects of static stretching on
      peak torque, work, the joint angle at peak torque, acceleration time, isokinetic
      range of motion, mechanomyographic amplitude, and electromyographic amplitude of
      the rectus femoris during maximal concentric isokinetic leg extensions at 1.04
      and 5.23 rad x s(-1) in men and women. Ten women (mean +/- s: age 23.0 +/- 2.9
      years, stature 1.61 +/- 0.12 m, mass 63.3 +/- 9.9 kg) and eight men (age 21.4 +/-
      3.0 years, stature 1.83 +/- 0.11 m, mass 83.1 +/- 15.2 kg) performed maximal
      voluntary concentric isokinetic leg extensions at 1.04 and 5.23 rad x s(-1).
      Following the initial isokinetic tests, the dominant leg extensors were stretched
      using four static stretching exercises. After the stretching, the isokinetic
      tests were repeated. Peak torque, acceleration time, and electromyographic
      amplitude decreased (P< or = 0.05) from pre- to post-stretching at 1.04 and 5.23
      rad . s(-1); there were no changes (P > 0.05) in work, joint angle at peak
      torque, isokinetic range of motion, or mechanomyographic amplitude. These
      findings indicate no stretching-related changes in the area under the angle -
      torque curve (work), but a significant decrease in peak torque, which suggests
      that static stretching may cause a "flattening" of the angle - torque curve that
      reduces peak strength but allows for greater force production at other joint
      angles. These findings, in conjunction with the increased limb acceleration rates
      (decreased acceleration time) observed in the present study, provide tentative
      support for the hypothesis that static stretching alters the angle - torque
      relationship and/or sarcomere shortening velocity.

PMID- 17454537
TI  - Influences of volitional and forced intentions on physical activity and effort
      within the theory of planned behaviour.
AB  - In the present study, we examined the utility of volitional and forced intentions
      in predicting participation in physical activities and effort within the theory
      of planned behaviour. Four hundred and forty-four participants (184 males, 260
      females) aged 19.1 +/- 3.3 years (mean +/- s) completed self-report measures of
      intentions, attitudes, subjective norms, perceived behavioural control,
      volitional intentions, forced intentions, and past behaviour in a physical
      activity context. Six weeks later, they completed self-report measures of
      physical activity behaviour and effort. Results indicated that volitional
      intentions and forced intentions contributed to the prediction of effort over and
      above intentions, attitudes, subjective norms, perceptions of control, past
      behaviour, and the product terms of attitudesxintentions and subjective
      normsxintentions. Volitional intentions and forced intentions did not predict
      participation in physical activities over and above effort. We concluded that
      volitional intentions and forced intentions assist in the explanation of effort
      in the context of physical activity behaviour.

PMID- 17454538
TI  - The effect of crank rate strategy on peak aerobic power and peak physiological
      responses during arm crank ergometry.
AB  - The main aim of this study was to determine whether the use of an imposed or
      freely chosen crank rate would influence submaximal and peak physiological
      responses during arm crank ergometry. Fifteen physically active men participated
      in the study. Their mean age, height, and body mass were 25.9 (s = 6.2) years,
      1.80 (s = 0.10) m, and 78.4 (s = 6.1) kg, respectively. The participants
      performed two incremental peak oxygen consumption (VO(2peak)) tests using an
      electronically braked ergometer. One test was performed using an imposed crank
      rate of 80 rev x min(-1), whereas in the other the participants used
      spontaneously chosen crank rates. The order in which the tests were performed was
      randomized, and they were separated by at least 2 days. Respiratory data were
      collected using an on-line gas analysis system, and fingertip capillary blood
      samples ( approximately 20 microl) were collected for the determination of blood
      lactate concentration. Heart rate was also recorded throughout the tests. Time to
      exhaustion was measured and peak aerobic power calculated. Submaximal data were
      analysed using separate two-way repeated-measures analyses of variance, while
      differences in peak values were analysed using separate paired t-tests.
      Variations in spontaneously chosen crank rate were assessed using a one-way
      analysis of variance with repeated measures. Agreement between the crank rate
      strategies for the assessment of peak values was examined by calculating intra
      class correlation coefficients (ICC) and 95% limits of agreement (95% LoA). While
      considerable between-participant variations in spontaneously chosen crank rate
      were observed, the mean value was not different (P > 0.05) from the imposed crank
      rate of 80 rev x min(-1) at any point. No differences (P > 0.05) were observed
      for submaximal data between crank strategies. Furthermore, mean peak minute power
      [158 (s = 20) vs. 158 (s = 18) W], time to exhaustion [739 (s = 118) vs. 727 (s =
      111) s], and VO(2peak)[3.09 (s = 0.38) vs. 3.04 (s = 0.34) l x min(-1)] were
      similar for the imposed and spontaneously chosen crank rates, respectively.
      However, the agreement for the assessment of VO(2peak) (ICC = 0.78; 95% LoA =
      0.04 +/- 0.50 l x min(-1)) between the cranking strategies was considered
      unacceptable. Our results suggest that either an imposed or spontaneously chosen
      crank rate strategy can be used to examine physiological responses during arm
      crank ergometry, although it is recommended that the two crank strategies should
      not be used interchangeably.

PMID- 17454539
TI  - Route choice in mountain navigation, Naismith's rule, and the equivalence of
      distance and climb.
AB  - In this paper, I consider decision making about routes in mountain navigation. In
      particular, I discuss Naismith's rule, a method of calculating journey times in
      mountainous terrain, and its use for route choice. The rule is essentially
      concerned with the equivalence, in terms of time duration, between climb or
      ascent and distance travelled. Naismith himself described a rule that is
      purported to be based on trigonometry and simple assumptions about rate of
      ascent; his rule with regard to hill-walking implies that 1 m of ascent is
      equivalent to 7.92 m of horizontal travel (1:7.92). The analysis of data on fell
      running records presented here supports Naismith's rule and it is recommended
      that male runners and walkers use a 1:8 equivalence ratio and females a 1:10
      ratio. The present findings are contrasted with those based on the analysis of
      data relating to treadmill running experiments (1:3.3), and with those based on
      the analysis of times for a mountain road-relay (1:4.4). Analysis of cycling data
      suggests a similar rule (1:8.2) for cycling on mountainous roads and tracks.

PMID- 17454541
TI  - Ball launch conditions for skilled golfers using drivers of different lengths in
      an indoor testing facility.
AB  - The displacement of the golf ball struck by a driving club is affected by several
      player characteristics and equipment parameters and their interrelationships.
      Some modelling and simulation studies have shown a relationship between shaft
      length and clubhead speed, supported by a few experimental studies. The aim of
      the present study was to examine the relationship between driver length and ball
      launch conditions in an indoor test facility using a ball launch monitor. Nine
      males considered to be skilled golfers participated in the study. Four driving
      clubs of total length 117, 119, 124, and 132 cm were assembled from commercially
      available components and were used to strike golf shots while initial ball
      velocity, backspin rate, and launch angles were measured. Statistical analysis
      identified a significant difference in initial launch speed due to club length, a
      significant difference between participants, but no difference between the trials
      for a given golfer. A positive trend was noted between backspin and launch angle
      for all four clubs, and significant inverse associations between initial launch
      speed and backspin rate and launch angle. However, the combined launch conditions
      associated with increasing length were not considered optimal, with uncontrolled
      swingweight and moment of inertia effects considered to be limiting factors.

PMID- 17454542
TI  - An examination of the planar nature of golf club motion in the swings of
      experienced players.
AB  - The golf swing has been modelled as a planar movement, but recent findings
      suggest that the upper limbs and golf club do not move in a single plane.
      However, the idea that the club alone can be swung in a single inclined plane has
      not been investigated mathematically. The aims of this study were to determine
      whether a single plane could be fitted to club motion, and if this plane varied
      for different clubs. Ten golfers (handicap 1-5) performed repeated, consistent
      swings with three clubs (driver, 5-iron, and pitching wedge). The motion of each
      club during the downswing was fitted to a single plane. The fit of the plane
      varied between golfers and clubs (r(2) = 0.871-0.995, root mean square residual =
      44.9-166.2 mm). Mean angles of the plane to the reference horizontal Z axis
      (driver: 125.5 degrees , s = 3.0; 5-iron: 117.1 degrees , s = 3.0; wedge: 113.6
      degrees , s = 2.7) and target line axis (driver: -7.8 degrees , s = 5.9; 5-iron: 
      4.9 degrees , s = 5.7; wedge: -5.9 degrees , s = 6.0) were significantly (P <
      0.05) different. Further analysis revealed a single plane was more appropriate
      for some participants than others, but that it might be neither desirable nor
      possible in some cases.

PMID- 17454543
TI  - The measurement of upper body alignment during the golf drive.
AB  - Transverse plane rotations of the upper body are often estimated during the golf
      swing. The aim of this study was to determine the agreement between upper body
      alignments measured using markers attached to the thorax and markers on the
      acromion process during the golf drive. Three-dimensional coordinate data from
      nine markers were collected (300 Hz) during eight golf drives for 10
      participants. The transverse plane alignment of the upper body was calculated
      using three techniques: inter-acromion vector, thorax vector, and Cardan angles.
      Agreement between the methods was then assessed using intra-class correlation and
      95% limits of agreement. Our results suggested that the thorax vector can be used
      to provide an accurate estimation of thorax alignment at all stages of the golf
      swing (R > or = 0.97, systematic difference < 1.0 degrees , random difference <
      3.8 degrees ). The inter-acromion vector gave an accurate estimation of thorax
      alignment at address (R = 0.90, systematic difference = 0.0 degrees , random
      difference = 4.3 degrees ) but it should not be used to estimate thorax alignment
      at the top of the backswing (R = 0.32, systematic difference = -16.0 degrees ,
      random difference = 8.7 degrees ) or impact (R = 0.90, systematic difference = 
      5.1 degrees , random difference = 8.3 degrees ) during the golf drive.

PMID- 17454544
TI  - Different centre of pressure patterns within the golf stroke I: Cluster analysis.
AB  - Weight transfer research in the golf swing has produced conflicting and
      inconclusive results. A limitation of previous studies is the assumption that
      only one swing "style" exists within the golf swing. If different styles, or
      movement strategies, exist and if the different styles are analysed together in a
      single group, statistical errors will result. The aim of this study was to
      determine if different weight transfer styles exist in the golf swing by applying
      cluster analysis to centre of pressure (CP) patterns in the direction of hit
      (CPy) and to evaluate cluster analysis issues. Sixty-two professional to high
      handicap golfers performed simulated drives, hitting a golf ball into a net,
      while standing on two force plates. Centre of pressure position relative to the
      feet (CPy%) was quantified at eight swing events identified from 200-Hz video.
      Cluster analysis identified two major CPy% styles: a "Front Foot" style and a
      "Reverse" style. Both styles began with CPy% positioned evenly between the feet,
      moved to the back foot during backswing, and then forward during early downswing.
      Beyond early downswing, the Front Foot group continued to move CPy% to the Front
      Foot through to ball contact, while the Reverse group moved CPy% towards the back
      foot through ball contact and follow-through. Both weight transfer styles were
      evident across skill levels from professional to high handicap golfers,
      indicating that neither style was a technical error. Cluster analysis should
      include hierarchical and non-hierarchical clustering and use objective measures
      combined with theoretical assessment to determine the optimal number of clusters.
      Furthermore, a number of validation procedures should always be used to validate
      the solution.

PMID- 17454545
TI  - Different centre of pressure patterns within the golf stroke II: group-based
      analysis.
AB  - Although the golf coaching literature stresses the importance of weight transfer
      during the swing, research has been conflicting or lacking statistical support. A
      potential problem with previous studies is that no attempt was made to account
      for different movement strategies in the golf swing. This study evaluated the
      relationship between centre of pressure measures and club head velocity within
      two previously identified swing styles, the "Front Foot" and "Reverse" styles.
      Thirty-nine Front Foot golfers and 19 Reverse golfers performed swings with a
      driver while standing on two force plates. From the force plate data, centre of
      pressure displacement, velocity, range, and timing parameters were calculated.
      Correlation and regression analysis indicated that a larger range of centre of
      pressure and a more rapid centre of pressure movement in the downswing was
      associated with a larger club head velocity at ball contact for the Front Foot
      group. For the Reverse golfers, positioning the centre of pressure further from
      the back foot at late backswing and a more rapid centre of pressure transfer
      towards the back foot at ball contact was associated with a larger club head
      velocity at ball contact. This study has highlighted the importance of
      identifying different movement strategies before evaluating performance measures,
      as different parameters were found to be important for the Front Foot and Reverse
      styles.

PMID- 17454546
TI  - Drinking guidelines for exercise: what evidence is there that athletes should
      drink "as much as tolerable", "to replace the weight lost during exercise" or "ad
      libitum"?
AB  - The most recent (1996) drinking guidelines of the American College of Sports
      Medicine (ACSM) propose that athletes should drink "as much as tolerable" during
      exercise. Since some individuals can tolerate rates of free water ingestion that
      exceed their rates of free water loss during exercise, this advice has caused
      some to overdrink leading to water retention, weight gain and, in a few, death
      from exercise-associated hyponatraemic encephalopathy. The new drinking
      guidelines of the International Olympic Committee (IOC), recently re-published in
      this Journal, continue to argue that athletes must drink enough to replace all
      their weight lost during exercise and to ingest sodium chloride since sodium is
      "the electrolyte most critical to performance and health". In this rebuttal to
      that Consensus Document, I argue that these new guidelines, like their
      predecessors, lack an adequate, scientifically proven evidence base. Nor have
      they been properly evaluated in appropriately controlled, randomized, prospective
      clinical trials. In particular, these new guidelines provide erroneous
      recommendations on five topics. If novel universal guidelines for fluid ingestion
      during exercise are to be promulgated by important international bodies including
      the IOC, they should first be properly evaluated in appropriately controlled,
      randomized, prospective clinical trials conducted under environmental and other
      conditions that match those found in "out-of-doors" exercise. This, and the
      potential influence of commercial interests on scientific independence and
      objectivity, are the two most important lessons to be learned from the premature
      adoption of those 1996 ACSM drinking guidelines that are not evidence-based.
      These concerns need to be addressed before the novel IOC guidelines are accepted
      uncritically. Otherwise the predictable consequences of the premature adoption of
      the 1996 ACSM guidelines will be repeated.

PMID- 17454547
TI  - Errors in the estimation of hydration status from changes in body mass.
AB  - Hydration status is not easily measured, but acute changes in hydration status
      are often estimated from body mass change. Changes in body mass are also often
      used as a proxy measure for sweat losses. There are, however, several sources of
      error that may give rise to misleading results, and our aim in this paper is to
      quantify these potential errors. Respiratory water losses can be substantial
      during hard work in dry environments. Mass loss also results from substrate
      oxidation, but this generates water of oxidation which is added to the body water
      pool, thus dissociating changes in body mass and hydration status: fat oxidation
      actually results in a net gain in body mass as the mass of carbon dioxide
      generated is less than the mass of oxygen consumed. Water stored with muscle
      glycogen is presumed to be made available as endogenous carbohydrate stores are
      oxidized. Fluid ingestion and sweat loss complicate the picture by altering body
      water distribution. Loss of hypotonic sweat results in increased osmolality of
      body fluids. Urine and faecal losses can be measured easily, but changes in the
      water content of the bladder and the gastrointestinal tract cannot. Body mass
      change is not always a reliable measure of changes in hydration status and
      substantial loss of mass may occur without an effective net negative fluid
      balance.

PMID- 17454548
TI  - Activity profile of top-class association football referees in relation to
      performance in selected physical tests.
AB  - The aims of the present study were (1) to analyse the physical demands of top
      class referees and (2) to compare their official FIFA fitness test results with
      physical performance during a match. The work rate profiles of 11 international
      referees were assessed during 12 competitive matches at the 2003 FIFA Under-17
      World Cup and then analysed using a bi-dimensional photogrammetric video analysis
      system based on direct lineal transformation (DLT) algorithms. In the first 15
      min of matches, the referees were more active, performing more high-intensity
      exercise (P < 0.01) than in the first 15 min of the second half. During the
      second half of matches, the referees covered a shorter distance (P < 0.01), spent
      more time standing still (P < 0.05), and covered less ground cruising (P < 0.05),
      sprinting (P < 0.05), and moving backwards (P < 0.001) than in the first half.
      Also in the second 45 min, the distance of referees from infringements increased
      (P < 0.05) in the left attacking zone of the filed. There was also a decrease (P
      < 0.05) in performance in the period following the most high-intensity activity,
      compared with the mean for the 90 min. Time spent performing high-intensity
      activities during a match was not related to performance in the 12-min run (r(2)
      = 0.30; P < 0.05), the 200-m sprint (r(2) = 0.05; P < 0.05), or the 50-m sprint
      (r(2) = 0.001; P < 0.05). The results of this study show that: (1) top-class
      referees experienced fatigue at different stages of the match, and (2) the
      typical field tests used by FIFA (two 50-m and 200-m sprints, followed by a 12
      min run) are not correlated with match activities.

PMID- 17454549
TI  - The physiological cost of velocity coupling during tennis groundstrokes.
AB  - Velocity coupling denotes a perceptual motor behaviour known to occur during
      coincidence timing tasks. Individuals have been shown to increase their effector
      limb speed with increases in stimulus speed during interceptive tasks. However,
      little is known about the physiological effects of velocity coupling. The aim of
      this study was to determine the physiological cost of velocity coupling during
      tennis groundstrokes. Eight male and eight female competitive tennis players
      volunteered to perform three 4-min bouts of continuous groundstrokes against
      balls projected from a tennis ball machine at speeds of 18, 22, and 27 m x s(-1)
      (65, 79, and 97 km x h(-1)) and a frequency of 14 balls per minute, the order of
      which was counterbalanced. Breath-by-breath pulmonary gas exchange, heart rate,
      locomotion time, and limb acceleration were measured throughout each of the 4-min
      bouts. Capillary blood samples (for blood lactate analysis), rating of perceived
      exertion, and difficulty rating were taken at the end of each bout. Increasing
      ball speed did not influence the locomotion time between groundstrokes but did
      result in a bilateral increase in both the mean upper- and lower-limb
      acceleration (all P < 0.05). Velocity coupling behaviour increased oxygen uptake,
      blood lactate concentration, heart rate, rating of perceived exertion, and
      perceived task difficulty (all P < 0.05). It would appear, therefore, that
      velocity coupling influenced tennis groundstroke behaviour and indirectly
      modified the concurrent cardiopulmonary and metabolic responses.

PMID- 17454550
TI  - Prediction of visceral fat area at the umbilicus level using fat mass of the
      trunk: The validity of bioelectrical impedance analysis.
AB  - The aims of this study were to determine the validity of fat mass of the trunk as
      a predictor for visceral fat area at the umbilicus level and to develop equations
      to predict visceral fat mass at the umbilicus level using fat mass of the trunk
      measured by dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance
      analysis (BIA). The participants were 121 normal Japanese adults (69 males, 52
      females). Another 60 volunteer adults (34 males, 26 females) were recruited for
      examination of cross-validity. Altogether, 41 adults (15 males, 26 females) in
      the original group and 19 adults (7 males, 12 females) in the cross-validity
      group received BIA measurement. We measured fat mass by DXA and the BIA system,
      which was a single-frequency BIA with 8-point contact electrodes, and visceral
      fat area by computed tomography. We observed significant correlations for
      visceral fat area in waist circumference (0.56) and fat mass of the trunk
      measured by DXA (0.64). There was no significant difference in fat mass of the
      trunk between the DXA and BIA systems, but the BIA system tended to provide an
      underestimate compared with DXA. With combined fat mass of the trunk measured by
      DXA and waist circumference as predictors, visceral fat area was estimated by
      equation (1) (R = 0.87, R(2) = 0.76, standard error of the estimate = 20.9
      cm(2)). When substituting fat mass of the trunk measured by BIA into equation
      (1), there was no significant difference in visceral fat area between the
      reference and predicted values. An equation using fat mass of the trunk measured
      by BIA (equation 2) was obtained (R = 0.89, R(2) = 0.78, standard error of the
      estimate = 20.7 cm(2)), but a systematic error was found for the males. There was
      cross-validity in both equations. In conclusion, fat mass of the trunk is an
      effective predictor for the visceral fat area at the umbilicus level. Fat mass of
      the trunk measured by BIA might be a valid method to predict visceral fat,
      although further studies with larger samples taking into account the extent and
      type of obesity are required.

PMID- 17454551
TI  - Lower limb muscle strength and physical activity in healthy individuals
      approaching retirement.
AB  - The purpose of this study was to examine knee extensor/flexor muscle strength and
      physical activity in healthy males and females approaching retirement. Peak
      torques of the knee extensor and knee flexor muscle groups were measured
      bilaterally in 95 individuals (mean age 59.4 years) using an isokinetic
      dynamometer. Isokinetic concentric contractions were performed at angular
      velocities of 1.05 and 3.14 rad x s(-1). Physical activity, including household,
      leisure, and sporting activities, was assessed. The results show that the average
      peak torques exhibited were lower than previously reported in studies using the
      same methodology with different populations of similar age and body size. Over
      one-third of the participants were sedentary, with just 13% being active enough
      to obtain health benefits. The poor muscle strength and low physical activity of
      this self selecting group of healthy working adults were surprising, and
      potentially a cause for concern. The combination of retirement being a potential
      watershed for a decrease in physical activity and the known age-related decline
      in physical performance indicates that some of these participants are at risk of
      losing their functional independence fairly early in the retirement stage. We
      recommend the introduction of effective health promotion interventions for
      individuals approaching retirement, encouraging them to become more physically
      active.

PMID- 17454552
TI  - Copper and human health: biochemistry, genetics, and strategies for modeling dose
      response relationships.
AB  - Copper (Cu) and its alloys are used extensively in domestic and industrial
      applications. Cu is also an essential element in mammalian nutrition. Since both
      copper deficiency and copper excess produce adverse health effects, the dose
      response curve is U-shaped, although the precise form has not yet been well
      characterized. Many animal and human studies were conducted on copper to provide
      a rich database from which data suitable for modeling the dose-response
      relationship for copper may be extracted. Possible dose-response modeling
      strategies are considered in this review, including those based on the benchmark
      dose and categorical regression. The usefulness of biologically based dose
      response modeling techniques in understanding copper toxicity was difficult to
      assess at this time since the mechanisms underlying copper-induced toxicity have
      yet to be fully elucidated. A dose-response modeling strategy for copper toxicity
      was proposed associated with both deficiency and excess. This modeling strategy
      was applied to multiple studies of copper-induced toxicity, standardized with
      respect to severity of adverse health outcomes and selected on the basis of
      criteria reflecting the quality and relevance of individual studies. The use of a
      comprehensive database on copper-induced toxicity is essential for dose-response
      modeling since there is insufficient information in any single study to
      adequately characterize copper dose-response relationships. The dose-response
      modeling strategy envisioned here is designed to determine whether the existing
      toxicity data for copper excess or deficiency may be effectively utilized in
      defining the limits of the homeostatic range in humans and other species. By
      considering alternative techniques for determining a point of departure and low
      dose extrapolation (including categorical regression, the benchmark dose, and
      identification of observed no-effect levels) this strategy will identify which
      techniques are most suitable for this purpose. This analysis also serves to
      identify areas in which additional data are needed to better define the
      characteristics of dose-response relationships for copper-induced toxicity in
      relation to excess or deficiency.

PMID- 17454553
TI  - Risk factors, health risks, and risk management for aircraft personnel and
      frequent flyers.
AB  - Health risks associated with long periods of time in flight are of concern to
      astronauts, crew members, and passengers. Many epidemiological studies showed
      that occupational and frequent flyers may be susceptible to ocular,
      cardiovascular, neurological, pulmonary, gastrointestinal, sensory,
      immunological, physiological, and even developmental disorders. In addition, the
      incidences of cancer and food poisoning are expected to be higher in such
      individuals. This article reviews health risks and risk factors associated with
      air travel, and discusses risk management strategies. To reduce adverse health
      risks, risk factors such as radiation, infection, stress, temperature, pressure,
      and circadian rhythm need to be avoided or reduced to levels that are as low as
      technologically achievable to protect flight personnel and passengers.

PMID- 17454554
TI  - Identification of urinary metabolites of orally administered N,N-dimethyl-p
      toluidine in male F344 rats.
AB  - The metabolism of orally administered N,N-dimethyl-p-toluidine (DMPT) in male
      F344 rats was investigated. The rat urinary metabolite profile was determined by
      analytical reverse-phase high performance liquid chromatography (HPLC). Four
      radiolabeled peaks were observed, isolated, and purified by solid-phase
      extraction (SPE) and preparative HPLC methods. The 4 peaks were identified as p
      (N-acetylhydroxyamino)hippuric acid (M1), DMPT N-oxide (M2), N-methyl-p-toluidine
      (M3), and parent DMPT. Metabolites M1 and M2 were identified by spectrometric and
      spectroscopic methods, including mass fragmentation pattern identification from
      both liquid chromatography/mass spectrometry and gas chromatography/mass
      spectrometry, and from chemical analysis of nuclear magnetic resonance spectra.
      Structural confirmation of metabolite M2 was accomplished by comparison with a
      synthetic standard. Peaks M3 and the peak suspected to be DMPT were identified by
      comparison of their HPLC retention times and mass fragmentation patterns with
      authentic standards of N-methyl-p-toluidine and DMPT, respectively. DMPT
      metabolism is similar to that reported for N,N-dimethylaniline.

PMID- 17454555
TI  - Disposition of [14C]N,N-dimethyl-p-toluidine in F344 rats and B6C3F1 mice.
AB  - N,N-Dimethyl-p-toluidine (DMPT) is used as a polymerization accelerator, in
      industrial glues, and as an intermediate in dye and pesticide synthesis. There is
      potential for human exposure to DMPT. The disposition of oral and intravenous
      (i.v.) doses of [14C]DMPT in F344 rats and B6C3F1 mice was investigated. A single
      i.v. (2.5 mg/kg) or oral (2.5, 25, or 250 mg/kg) dose of [14C]DMPT (1-25 microCi)
      was administered in an aqueous vehicle to male rats and mice. The 25-mg/kg oral
      dose was administered to females to investigate possible gender differences in
      disposition. However, no striking gender differences were observed. Since
      toxicity studies conducted elsewhere used a corn oil vehicle, the 250-mg/kg oral
      dose also was administered in corn oil to male rats; disposition was not
      dependent on vehicle. Excreta (through 24 h) and tissues collected at sacrifice
      were analyzed for total radioactivity. Dose-dependent differences in toxicity and
      disposition were observed. Toxicity at the 250-mg/kg oral dose to male mice was
      consistent with acute renal failure. At the same dose, male rats exhibited
      clinical signs of toxicity through 12 h but were clinically normal by 24 h. At
      lower oral doses, [14C]DMPT-derived radioactivity was well absorbed and rapidly
      excreted, primarily in urine.

PMID- 17454556
TI  - Mouse monocytes (RAW CELLS) and the handling of cysteine and homocysteine S
      conjugates of inorganic mercury and methylmercury.
AB  - Although there is evidence indicating that mononuclear phagocytes can take up
      mercury by some forms of endocytosis, very little is known about the potential
      for the uptake of mercuric species by carrier-mediated processes. Thus, we
      hypothesized that monocytes also possess mechanisms allowing these cells to take
      up inorganic mercury (Hg2+) and/or methylmercury (CH3Hg+) as cysteine (Cys)
      and/or homocysteine (Hcy) S-conjugates by certain membrane transport proteins.
      The specific thiol S-conjugates were chosen for study because our laboratory and
      those of some other investigators have demonstrated that these species of mercury
      are indeed transportable substrates for several membrane transport proteins in
      certain types of epithelial cells. We chose to use RAW 264.7 cells for our
      experiments. These cells represent an adherent line of mouse monocytes. Kinetic
      analyses for the uptake of Cys-Hg-Cys, CH3Hg-Cys, Hcy-Hg-Hcy, and CH3Hg-Hcy
      revealed that uptake occurred by a saturable, concentration-dependent mechanism,
      displaying Michaelis-Menten properties. Interestingly, in the cells exposed to
      the Cys or Hcy S-conjugate of Hg2+, significantly more Hg2+ was taken up in the
      presence of 140 mM sodium chloride (NaCl) than in the presence of 140 mM N-methyl
      D-glucamine (NMDG), indicating that Na-dependent processes play more of a role in
      the uptake of these species of Hg2+ than sodium-independent ones. With respect to
      the uptake of CH3Hg+, rates of uptake of the Cys and Hcy S-conjugates of CH3Hg+
      were similar under both Na-dependent and Na-independent conditions, although the
      levels of uptake of these mercuric species far exceeded the levels of uptake of
      the corresponding S-conjugate of Hg2+. Uptake of Hg2+ and CH3Hg+, as the Cys or
      Hcy S-conjugates, was also time-dependent. We also showed that when the
      temperature in the bathing medium was reduced to 4 degrees C, uptake of the Cys S
      conjugates Hg2+ or CH3Hg+ was for the most part reduced to negligible levels in
      the RAW cells; indicating that the preponderance of uptake at 37 degrees C was
      not due primarily to simple diffusion and/or non-specific binding. Overall, the
      present findings strongly suggest that the uptake of the Cys and Hcy S-conjugates
      of Hg2+ and/or CH3Hg+ occurs in monocytes by one or more mechanisms involving
      carrier proteins.

PMID- 17454557
TI  - Effects of chronic 137Cs ingestion on barrier properties of jejunal epithelium in
      rats.
AB  - Environmental contamination by 137Cs is of particular public health interest
      because of the various sources of fallout originating from nuclear weapons,
      radiological source disruptions, and the Chernobyl disaster. This dispersion may
      lead to a chronic ecosystem contamination and subsequent ingestion of
      contaminated foodstuffs. The aim of this study was to thus determine the impact
      of a chronic ingestion of low-dose 137Cs on small intestine functions in rats.
      The animals received 150 Bq per day in drinking water over 3 mo. At these
      environmental doses, 137Cs contamination did not modify the crypt and villus
      architecture. In addition, epithelial integrity was maintained following the
      chronic ingestion of 137Cs, as demonstrated by histological analyses (no
      breakdown of the surface mucosa) and electrical transepithelial parameters (no
      change in potential difference and tissue conductance). Furthermore, cesium
      contamination seemed to induce contradictory effects on the apoptosis pathway,
      with an increase in the gene expression of Fas/FasL and a decrease in the
      apoptotic cell number present in intestinal mucosa. No marked inflammation was
      observed following chronic ingestion of 137Cs, as indicated by neutrophil
      infiltration and gene expression of cytokines and chemokines. Results indicated
      no imbalance in the Th1/Th2 response induced by cesium at low doses. Finally,
      evaluation of the functionality of the jejunal epithelium in rats contaminated
      chronically with 137Cs did not demonstrate changes in the maximal response to
      carbachol, nor in the cholinergic sensitivity of rat jejunal epithelium. In
      conclusion, this study shows that chronic ingestion of 137Cs over 3 mo at
      postaccidental doses exerts few biological effects on the epithelium of rat
      jejunum with regard to morphology, inflammation status, apoptosis/proliferation
      processes, and secretory functions.

PMID- 17454558
TI  - Suppression of phagocytic and bactericidal functions of rat alveolar macrophages
      by the organic component of diesel exhaust particles.
AB  - Exposure to diesel exhaust particles (DEP) was shown to increase the
      susceptibility of the lung to bacterial infection in rats. In this study, the
      effects of DEP on alveolar macrophage (AM) phagocytic and bactericidal functions
      and cytokine secretion by AM and lymphocytes in response to Listeria
      monocytogenes infection were investigated in vitro and the roles of different DEP
      components in these processes were compared. Exposure to DEP or the organic
      extracts of DEP (eDEP) significantly decreased the phagocytosis and killing of L.
      monocytogenes by AM obtained from normal rats. Washed DEP (wDEP) also decreased
      AM phagocytosis and bacterial killing to a lesser extent, whereas carbon black
      (CB) reduced AM phagocytosis but had no significant effect on AM bactericidal
      activity. DEP or eDEP concentration-dependently suppressed L. monocytogenes
      induced secretion of tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL
      12 by AM and of IL-2 and interferon-gamma by lymphocytes obtained from L.
      monocytogenes-infected rats, but augmented the AM secretion of IL-10. wDEP or CB,
      however, exerted little or no effect on these L. monocytogenes-induced cytokines.
      These results provide direct evidence that DEP, through the actions of organic
      components, suppresses AM phagocytic and bactericidal functions in vitro.
      Inhibition of AM phagocytic function and alterations of AM and lymphocyte
      cytokine secretion by DEP and DEP organic compounds may be implicated in the
      diminished AM bactericidal activity and the lymphatic arm of the host immune
      system, thus resulting in an suppressed pulmonary clearance of L. monocytogenes
      and an increased susceptibility of the lung to bacterial infection.

PMID- 17454559
TI  - Disposition and clearance of tungsten after single-dose oral and intravenous
      exposure in rodents.
AB  - Tungsten (W) has been nominated for study to the National Toxicology Program
      (NTP) because of reported associations between concentrations of W in drinking
      water and childhood leukemia. The disposition of W (administered as sodium
      tungstate dihydrate in water) in plasma, liver, kidneys, uterus, femur, and
      intestine of rodents (Sprague-Dawley rats and C57BL/6N mice) was characterized
      after exposures by oral gavage (1, 10, or 100 mg/kg) or intravenous (1 mg/kg)
      administration. Each tissue (or plasma) was collected and analyzed by inductively
      coupled plasma mass spectrometry at 1, 2, 4, or 24 h after dose administration. W
      was observed in plasma and all tissues after both gavage and i.v. administration.
      In rats, concentrations in plasma and most tissues peaked at 4 h. In mice,
      concentrations in plasma and most tissues peaked at 1 h. Although the amount of W
      in each matrix decreased significantly by 24 h, there was W remaining in several
      tissues, especially at the higher doses.

PMID- 17454560
TI  - A case series of children with apparent mercury toxic encephalopathies
      manifesting with clinical symptoms of regressive autistic disorders.
AB  - Impairments in social relatedness and communication, repetitive behaviors, and
      stereotypic abnormal movement patterns characterize autism spectrum disorders
      (ASDs). It is clear that while genetic factors are important to the pathogenesis
      of ASDs, mercury exposure can induce immune, sensory, neurological, motor, and
      behavioral dysfunctions similar to traits defining or associated with ASDs. The
      Institutional Review Board of the Institute for Chronic Illnesses (Office for
      Human Research Protections, U.S. Department of Health and Human Services, IRB
      number IRB00005375) approved the present study. A case series of nine patients
      who presented to the Genetic Centers of America for a genetic/developmental
      evaluation are discussed. Eight of nine patients (one patient was found to have
      an ASD due to Rett's syndrome) (a) had regressive ASDs; (b) had elevated levels
      of androgens; (c) excreted significant amounts of mercury post chelation
      challenge; (d) had biochemical evidence of decreased function in their
      glutathione pathways; (e) had no known significant mercury exposure except from
      Thimerosal-containing vaccines/Rho(D)-immune globulin preparations; and (f) had
      alternate causes for their regressive ASDs ruled out. There was a significant
      dose-response relationship between the severity of the regressive ASDs observed
      and the total mercury dose children received from Thimerosal-containing
      vaccines/Rho (D)-immune globulin preparations. Based upon differential diagnoses,
      8 of 9 patients examined were exposed to significant mercury from Thimerosal
      containing biologic/vaccine preparations during their fetal/infant developmental
      periods, and subsequently, between 12 and 24 mo of age, these previously normally
      developing children suffered mercury toxic encephalopathies that manifested with
      clinical symptoms consistent with regressive ASDs. Evidence for mercury
      intoxication should be considered in the differential diagnosis as contributing
      to some regressive ASDs.

PMID- 17454561
TI  - Comparative cytotoxicity of cadmium and mercury in a human bronchial epithelial
      cell line (BEAS-2B) and its role in oxidative stress and induction of heat shock
      protein 70.
AB  - A number of toxic heavy metals, such as cadmium (Cd) and mercury (Hg), are widely
      used in occupational settings, and exposure to these metals is associated with
      the development of pulmonary diseases. Cytotoxicity, apoptosis, and reactive
      oxygen species (ROS) generation were tested to compare the biological reactivity
      of these two heavy metals using a human bronchial epithelial cell line, BEAS-2B.
      Further, heat-shock protein 70 (Hsp70) expression was observed as a sensitive
      indicator of cellular stress. Exposure to metals (0-50 microM) for 72 h showed
      more significant cytotoxicity in Cd-treated than Hg-treated cells. Apoptosis was
      significantly increased in the cells exposed to 50 microM of Cd (3.5-fold) and Hg
      (3.6-fold). Cd and Hg produced an induction of Hsp70 protein as assayed by
      Western blotting and enzyme-linked immunosorbent assay (ELISA). Induction of
      Hsp70 protein by these metals was inhibited by addition of N-acetylcysteine.
      However, addition of catalase blocked the synthesis of Hsp70 only in Hg-treated
      cells. Hsp70B and Hsp70C mRNA expression was induced by both metals, while Hsp70A
      mRNA expression showed no change. Electron spin resonance (ESR) tests showed that
      hydroxyl radical generation was greater in the reaction of cells with Hg compared
      to Cd. Intracellular generation of ROS was detected in the cells exposed to both
      Cd and Hg. These results suggest that both cytotoxicity and apoptosis were
      significantly elevated with all metals tested; however, Cd was relatively more
      toxic. Hsp70 protein and mRNA were sensitive to exposure to these metals.
      Depletion of sulfhydryl groups of cellular proteins and generation of ROS may be
      involved in metal-induced lung cell damage.

PMID- 17454562
TI  - Effects of dietary selenium on tissue concentrations, pathology, oxidative
      stress, and immune function in common eiders (Somateria mollissima).
AB  - Common eiders (Somateria mollissima) were fed added Se (as L-selenomethionine) in
      concentrations increasing from 10 to 80 ppm in a pilot study (Study 1) or 20 (low
      exposure) and up to 60 (high exposure) ppm Se in Study 2. Body weights of Study 1
      ducks and high-exposure ducks in Study 2 declined rapidly. Mean concentrations of
      Se in blood reached 32.4 ppm wet weight in Study 1 and 17.5 ppm wet weight in
      high-exposure birds in Study 2. Mean Se concentrations in liver ranged from 351
      (low exposure, Study 2) to 1252 ppm dry weight (Study 1). Oxidative stress was
      evidenced by Se-associated effects on glutathione metabolism. As Se
      concentrations in liver increased, Se-dependent glutathione peroxidase activity,
      glutathione reductase activity, oxidized glutathione levels, and the ratio of
      hepatic oxidized to reduced glutathione increased. In Study 2, the T-cell
      mediated immune response was adversely affected in high-exposure eiders, but
      ducks in the low-exposure group exhibited evidence of an enhanced antibody
      mediated immune response. Gross lesions in high-exposure ducks included
      emaciation, absence of thymus, and loss of nails from digits. Histologic lesions
      included severe depletion of lymphoid organs, hepatopathy, and necrosis of
      feather pulp and feather epithelium. Field studies showed that apparently healthy
      sea ducks generally have higher levels of Se in liver than healthy fresh-water
      birds, but lower than concentrations found in our study. Data indicate that
      common eiders and probably other sea ducks possess a higher threshold, or adverse
      effect level, for Se in tissues than fresh-water species. However, common eiders
      developed signs of Se toxicity similar to those seen in fresh-water birds.

PMID- 17454563
TI  - Toxicokinetic relationship between di(2-ethylhexyl) phthalate (DEHP) and mono(2
      ethylhexyl) phthalate in rats.
AB  - The toxicokinetic relationship between di(2-ethylhexyl) phthalate (DEHP) and
      mono(2-ethylhexyl) phthalate (MEHP), a major metabolite of DEHP, was investigated
      in Sprague-Dawley rats orally treated with a single dose of 14C-DEHP. Urinary
      excretion of total 14C-DEHP and of its metabolites was followed by liquid
      scintillation counting (LSC). Concentrations of DEHP and MEHP were determined 6,
      24, and 48 h after treatment in rat serum and 6, 12, 24, and 48 h after treatment
      in urine by high-performance liquid chromatography (HPLC). After 24 h, peak
      concentrations of MEHP in both urine and serum were observed in animals treated
      with 40, 200, or 1000 mg DEHP/kg. HPLC showed that general toxicokinetic
      parameters, such as Tmax (h), Cmax (microg/ml), Ke (1/h), and AUC (microg-h/ml/)
      were greater for MEHP than DEHP in both urine and serum. In contrast, the half
      lives (t1/2 [h]) of DEHP were greater than those of MEHP. The AUC ratios between
      DEHP and MEHP were relatively smaller in serum than in urine, suggesting the
      important role of urinary DEHP data for exposure assessment of DEHP. The
      toxicokinetic relationship between DEHP and MEHP in rats suggests that DEHP
      exposure assessment should be based on DEHP and MEHP in urine and serum for risk
      assessment applications.

PMID- 17454564
TI  - Evaluation of the genotoxicity of (-)-hydroxycitric acid (HCA-SX) isolated from
      Garcinia cambogia.
AB  - (-)-Hydroxycitric acid (HCA) is widely used as an ingredient for nutritional
      supplements aimed at reducing food intake, appetite, and body weight. In this
      study, the genotoxicity of HCA was evaluated using three tests: a bacterial
      reverse mutation assay (Ames test), an in vitro chromosomal aberration (CA) test,
      and an in vivo micronucleus (MN) test. HCA was negative by the Ames test in the
      presence or absence of a microsomal metabolizing system. HCA did not induce
      mutagenic activity in the Ames test, and no significant mutagenic potency was
      indicated by CA tests. However, HCA significantly and dose-dependently increased
      the number of MNPCEs (micronucleated polychromatic erythrocytes/1000
      polychromatic erythrocytes) and PCE/(PCE + NCE) ratios according to the MN test.
      These results suggest that HCA preferentially induce micronuclei.

PMID- 17454565
TI  - Inhibitory effects of plant extracts on tyrosinase, L-DOPA oxidation, and melanin
      synthesis.
AB  - For medical, pharmacological, and cosmetic reasons, the demand for effective and
      safe depigmentating agents has increased. In this study, 101 plant extracts
      (methanol or water extracts) were screened for their inhibitory activities
      against tyrosinase, (L-3, 4,-dihydroxyphenylalanine) L-DOPA oxidation, and
      melanin biosynthesis in B16 mouse melanoma cells. Of the extracts examined, 31
      showed over 50% inhibition of mushroom tyrosinase at a concentration of 666
      microg/Ml, and 11 inhibited L-DOPA auto-oxidation at this concentration. In
      particular, extracts of Broussonetia kazinoki var. humilis (leaves and stems),
      Broussonetia papyrifera (leaves and bark), Cornus officinalis (fruit), Rhus
      javanica (gallnut), and Pinus densiflora (leaves) inhibited both tyrosinase
      activity and L-DOPA oxidation in a concentration-dependent manner. Seventeen
      plant extracts that inhibited tyrosinase were further tested for their inhibitory
      effects on melanogenesis. In B16 mouse melanoma cells, extracts of Acorus
      gramineus, Capsella bursa-pastoris, Morus bombycis, Perilla frutescens var.
      crispa, Quercus dentate (bark), Rhus javanica (gallnut), Schizopepon
      bryoniaefolius, or Sophora flavescens markedly inhibited (>50%) melanin synthesis
      at 50 microg/Ml. These plants represent a potential source of novel whitening
      agents for ultraviolet (UV)-sensitive skin.

PMID- 17454566
TI  - Perchlorate and radioiodide kinetics across life stages in the human: using PBPK
      models to predict dosimetry and thyroid inhibition and sensitive subpopulations
      based on developmental stage.
AB  - Perchlorate (ClO4(-)) is a drinking-water contaminant, known to disrupt thyroid
      hormone homeostasis in rats. This effect has only been seen in humans at high
      doses, yet the potential for long term effects from developmental endocrine
      disruption emphasizes the need for improved understanding of perchlorate's effect
      during the perinatal period. Physiologically based pharmacokinetic/dynamic
      (PBPK/PD) models for ClO4(-) and its effect on thyroid iodide uptake were
      constructed for human gestation and lactation data. Chemical specific parameters
      were estimated from life-stage and species-specific relationships established in
      previously published models for various life-stages in the rat and nonpregnant
      adult human. With the appropriate physiological descriptions, these kinetic
      models successfully simulate radioiodide data culled from the literature for
      gestation and lactation, as well as ClO4(-) data from populations exposed to
      contaminated drinking water. These models provide a framework for extrapolating
      from chemical exposure in laboratory animals to human response, and support a
      more quantitative understanding of life-stage-specific susceptibility to ClO4(-).
      The pregnant and lactating woman, fetus, and nursing infant were predicted to
      have higher blood ClO4(-) concentrations and greater thyroid iodide uptake
      inhibition at a given drinking-water concentration than either the nonpregnant
      adult or the older child. The fetus is predicted to receive the greatest dose
      (per kilogram body weight) due to several factors, including placental sodium
      iodide symporter (NIS) activity and reduced maternal urinary clearance of ClO4(
      ). The predicted extent of iodide inhibition in the most sensitive population
      (fetus) is not significant (approximately 1%) at the U.S. Environmental
      Protection Agency reference dose (0.0007 mg/kg-d).

PMID- 17454567
TI  - Organ growth functions in maturing male Sprague-Dawley rats.
AB  - Growth equations can be used in physiologically based pharmacokinetic (PBPK)
      modeling to provide physiological parameters (e.g., body weight, tissue/organ
      volumes) for maturing rodents. No diligent systematic exercise was found in the
      literature dealing with growth equations for developing rats' tissues. A
      generalized Michaelis-Menten (GMM) model, originally developed to fit body weight
      vs. age data, was chosen to estimate different physiological compartment sizes.
      The GMM model has the functional form: Wt = (Wt(o).K(gamma) +
      Wt(max).Age(gamma))/(K(gamma) + Age(gamma)) where Wt is organ/tissue weight at a
      specified age, Wt(o) and Wt(max) are weight at birth and maximal growth
      respectively, and K and gamma are constants. Weights of freshly collected organs
      (liver, spleen, kidneys, heart, lungs, brain, gastrointestinal tract and adipose
      tissue), measured in male Sprague-Dawley rats of different ages (1-280 d) in our
      laboratory, were used to evaluate this model's performance. The GMM model was
      fitted to the organ weights, and the resulting parameters were statistically
      significant for all organs and tissues. Organ weights were highly correlated with
      their respective ages. GMM-derived organ growth and percent body weight (%BW)
      fractions of different tissues were plotted against animal age and compared with
      experimental values. The GMM-based organ growth and %BW fraction profiles were in
      general agreement with our empirical data as well as previous studies. The GMM
      model gave adequately precise weight predictions at all ages for all the
      tissues/organs examined.

PMID- 17454568
TI  - Differential sensitivity to anticholinesterase insecticides in the juvenile rat:
      effects on thermoregulation.
AB  - Organophosphate (OP) and carbamate (CB) insecticides inhibit cholinesterase (ChE)
      activity and induce acute hypothermia in adult rats. Studies showed that
      juveniles are generally more susceptible to neurotoxic insult than adults.
      However, little is known concerning the effects of OP and CB pesticides on
      thermoregulation in developing animals. Thus, alterations in core body
      temperature (Tc) in juvenile animals exposed to an OP and CB insecticide were
      investigated. Male rat pups were anesthetized on postnatal day (PND) 15 with
      metofane and a radio transmitter (Data Sciences) was implanted in the abdominal
      cavity to monitor Tc and motor activity (MA). Two days were allowed for recovery.
      The PND 17 pups were then dosed by oral gavage with the OP chlorpyrifos (CHP) (1,
      5, 10, or 15 mg/kg) or the CB carbaryl (CAR) (10, 20, 80, 120, or 160 mg/kg) or
      the corn oil vehicle. Pups were returned to their dams and littermates
      immediately after dosing and monitored for the next several days. CHP doses of 10
      and 15 mg/kg resulted in 1.0 degrees C and 2.4 degrees C reductions in Tc,
      respectively. Tc recovered to control levels by approximately 16 h after dosing.
      There was significant mortality in rats dosed with 15 mg/kg CHP (6 of 11). CAR
      doses of 10 to 80 mg/kg had little effect on Tc. The highest dose of CAR (160
      mg/kg) resulted in a 1.3 degrees C reduction in Tc that recovered in 9 h. In
      contrast, past studies found that adult male rats become hypothermic at CHP doses
      of >25 mg/kg, whereas a CAR dose of 50 mg/kg is effective at inducing
      hypothermia. Overall, it appears that during the development from preweanling to
      adult rat, there is a progressive attenuation in CHP-induced hypothermia.
      Conversely, CAR-induced hypothermia increases as a function of development.

PMID- 17454569
TI  - A pharmacokinetic model of the intracellular dosimetry of inhaled nickel.
AB  - The potential associations between exposure to nickel compounds and cancer have
      been evaluated in both animal and epidemiological studies of occupationally
      exposed workers. The results of the epidemiological studies suggest that not all
      nickel compounds are equally carcinogenic, an observation supported by the animal
      bioassay results. Given the complexity and the differences in the modes of uptake
      of different forms of nickel by cells and the subsequent delivery of nickel to
      the nucleus, it would be expected that some forms of nickel would be more potent
      than others. A physiologically based pharmacokinetic (PBPK) model would be useful
      in estimating the cellular exposure to nickel resulting from inhalation of the
      different forms of nickel. To this end, a preliminary model of a tracheobronchial
      epithelial cell was developed to describe the differences in the extracellular
      and intracellular kinetics of the different classes of nickel compounds. Data
      available in the published literature were used to define the initial model
      parameters. The resulting cellular dosimetry model was able to describe kinetic
      data on three forms of nickel (soluble chloride and insoluble sulfide and
      subsulfide). This preliminary model development effort has identified critical
      data gaps that could be filled by additional research. The ultimate goal will be
      to integrate a refined cellular dosimetry model with published lung
      deposition/clearance and systemic distribution/clearance models for nickel. The
      use of such an integrated PBPK model would allow for more biologically based risk
      estimates for the inhalation of the different nickel compounds, as well as
      mixtures of these compounds.

PMID- 17454570
TI  - Estimating volatile organic compound concentrations in selected microenvironments
      using time-activity and personal exposure data.
AB  - Repeated measures of personal exposure to 14 volatile organic compounds (VOC)
      were obtained over 3 seasons for 70 healthy, nonsmoking adults living in
      Minneapolis-St. Paul. Matched data were also available for participants' time
      activity patterns, and measured VOC concentrations outdoors in the community and
      indoors in residences. A novel modeling approach employing hierarchical Bayesian
      techniques was used to estimate VOC concentrations (posterior mode) and
      variability (credible intervals) in five microenvironments: (1) indoors at home;
      (2) indoors at work/school; (3) indoors in other locations; (4) outdoors in any
      location; and (5) in transit. Estimated concentrations tended to be highest in
      "other" indoor microenvironments (e.g., grocery stores, restaurants, shopping
      malls), intermediate in the indoor work/school and residential microenvironments,
      and lowest in the outside and in-transit microenvironments. Model estimates for
      all 14 VOC were reasonable approximations of measured median concentrations in
      the indoor residential microenvironment. The largest predicted contributor to
      cumulative (2-day) personal exposure for all 14 VOC was the indoor residential
      environment. Model-based results suggest that indoors-at-work/school and indoors
      at-other-location microenvironments were the second or third largest contributors
      for all VOC, while the outside-in-any-location and in-transit microenvironments
      appeared to contribute negligibly to cumulative personal exposure. Results from a
      mixed-effects model indicate that being in or near a garage increased personal
      exposure to o-xylene, m/p-xylene, benzene, ethylbenzene, and toluene, and leaving
      windows and doors at home open for 6 h or more decreased personal exposure to 13
      of 14 VOC, all except trichloroethylene.

PMID- 17454571
TI  - Visual laterality effects in readers of a deep and a shallow orthography.
AB  - Using a tachistoscopic split-field paradigm, hemifield asymmetry for single word
      recognition was examined in monolingual English speakers and in fluent bilingual
      English-Welsh speakers. A robust right hemifield advantage was found for both
      groups and both languages. Among bilinguals, the laterality index was
      significantly greater for Welsh than for English, supporting previous findings.
      The magnitude of the laterality index was unaffected by which language was
      learned first (Welsh or English) and by the age of acquisition (before or after 5
      6years old) of the second language. However, among bilinguals there was a
      significant difference in the laterality index for Welsh words compared with
      English words for those participants brought up in a predominantly Welsh-speaking
      environment, but not for those brought up in a predominantly English-speaking or
      dual-language environment. We attribute our results to the difference in
      orthographic depth between Welsh and English. and argue that the transparency of
      Welsh favours adoption of a left-hemisphere based phonological decoding strategy
      in reading. Such a strategy is not necessarily used exclusively by readers of
      Welsh, but is encouraged by regular exposure to the Welsh language on a day-to
      day basis.

PMID- 17454572
TI  - Lateralisation of emotion predicts infant-holding bias in left-handed students,
      but not in left-handed mothers.
AB  - It has been shown that most human beings prefer to hold an infant on the left
      side of the body. Several factors may be responsible for this behavioural bias.
      The present study tested the role of emotion-perception asymmetries (assessed
      with a dichotic listening task) in infant holding-side preferences. In order to
      neutralise the influence of handedness, only left-handers were recruited. A
      sample of students was compared to a sample of mothers, with a view to
      demonstrating that hemispheric specialisation influences holding-side biases in
      left-handers only in a basic holding relationship (population of non-parents
      tested on an imagination task). The results confirmed the relationship between
      holding-side preferences and auditory-field advantages solely for students. The
      role of the holder's characteristics in determining of holding biases is
      discussed.

PMID- 17454573
TI  - Constant error in aiming movements without visual feedback is higher in the
      preferred hand.
AB  - There is convincing evidence for a left hand advantage for the spatial planning
      of aiming movements in right-handers. However, little is known about equivalent
      proficiency in left-handers. Therefore, 48 participants (24 right-handers and 24
      left-handers) performed aiming movements of the hand without visual feedback.
      While the variable aiming error tended to be lower for the preferred hand, the
      constant aiming error was consistently lower for the non-preferred hand. Data are
      consistent with the idea of a spatial accuracy advantage for the controller of
      the non-preferred hand. Data from an ambidextrous participant suggest that this
      functional difference might be innate rather than acquired through practice.

PMID- 17454574
TI  - Sensitivity of functional tympanic membrane thermometry (fTMT) as an index of
      hemispheric activation in cognition.
AB  - The measure of hemispheric activation in cognitive and clinical studies remains
      out of reach of many scientists due to cost, analysis complexity, and practical
      consideration of the techniques available such as fMRI, EEG, or EMG. The present
      study was conducted to determine whether infrared functional tympanic membrane
      thermometry (fTMT) is a measure of lateralised activation sensitive enough to be
      used in typical cognitive and clinical experiments. A total of 24 participants
      had their tympanic membrane temperature measured while performing a letter
      matching task. Activation in the two hemispheres was manipulated by changing the
      proportion of matches occurring in the left and right visual fields and by
      varying the task complexity. Changes in fTMT due to the greater proportion of
      matches presented in one visual field and due to the modulation in task
      complexity were detected. These findings suggest that fTMT is a measure of broad
      lateralised cerebral activation sensitive enough for use in typical psychological
      studies.

PMID- 17454575
TI  - Attention in musicians is more bilateral than in non-musicians.
AB  - Attention in neurologically intact adults normally errs towards the left side of
      space, as documented in studies involving tasks of visual attention (i.e., line
      bisection). The aim of this study was to further investigate lateralisation of
      attention in musicians and non-musicians. Reaction times and accuracy were
      recorded to stimuli presented to the left and right of a vertical line in 20
      right-handed musicians and 20 matched non-musician controls. While both groups
      performed more accurately to left-sided stimuli, performance by the musician
      group was significantly more accurate than the non-musician group for the right
      sided stimuli. Musicians also had faster reaction times overall. Consistent with
      previous research, the results indicate a more balanced attentional capacity in
      musicians, as well as enhanced visuomotor ability, and are interpreted with
      reference to extended musical training.

PMID- 17454576
TI  - A cross-cultural comparison of pressures to switch left-hand writing: Brazil
      versus Canada.
AB  - Attempts to switch left-hand preferences towards the right side are socialisation
      practices found in many countries (Perelle & Ehrman, 1994). Although researchers
      acknowledge that pressures against left-hand use contribute to the cross-cultural
      fluctuations in the prevalence of left- versus right-hand preference, there has
      been little systematic cross-cultural study of how these pressures are applied,
      and who are the major agents applying the pressures to change. Our study explored
      specific rightward conversion practices and the results of these practices among
      individuals from two countries. One sample of participants was from a culture
      categorised as formal, Brazil, and the second sample was from Canada, a nonformal
      culture (Hofstede, 2001). Researchers have argued that prevalence rates of right
      handedness should be higher in cultures that value conformity, called formal
      cultures, and lower among members of nonformal cultures where conformity
      pressures are lax (Medland, Perelle, De Monte, & Ehrman, 2004). The socialisation
      practices used to foster a change from the left to the right side are also
      predicted to differ in frequency and in kind in formal versus nonformal cultural
      settings. These cultural differences are assumed to result in differences in
      success rates of the conversion attempts, with formal cultures producing higher
      numbers of successfully converted right-handers. Our findings indicate that the
      formal versus nonformal cultural explanation for cross-cultural fluctuations in
      the prevalence of hand preference types does not account for the characteristics
      of the rightward conversion experiences reported by participants in the two
      groups. We propose that hypotheses concerning the effects of cultural differences
      on hand preference formation be expanded to include possible biological or
      genetic variance between groups.

PMID- 17454578
TI  - A new PML-RARs fusion transcript hints at the important role of PML dysregulation
      in the pathogenesis of APL.

PMID- 17454579
TI  - Is there still a role for interferon-alpha for newly diagnosed chronic myeloid
      leukemia in chronic phase?

PMID- 17454580
TI  - Overcoming mechanisms of RECISTance in lymphoma.

PMID- 17454581
TI  - Angioimmunoblastic T-cell lymphoma: immune modulation as a therapeutic strategy.

PMID- 17454582
TI  - What is the optimal prognostic tool for the assessment of patients with newly
      diagnosed follicular lymphoma?

PMID- 17454583
TI  - Antiangiogenesis: a new approach to the treatment of lymphoma.

PMID- 17454584
TI  - WT1 expression in myelodysplastic syndrome.

PMID- 17454585
TI  - Relevant prognostic features of multiple myeloma and the new International
      Staging System.
AB  - The new International Staging System should be reported in all future studies of
      multiple myeloma. However, the system fails to account for recent research
      findings pertaining to mechanisms of disease progression. This review describes
      development of the International Staging System and details prognostic factors
      that may further our understanding of the biology of multiple myeloma.

PMID- 17454586
TI  - The treatment of the elderly multiple myeloma patients.
AB  - Multiple myeloma (MM) is an incurable malignancy of the plasma cells. Most
      patients are diagnosed when they are older than 65 years. Therapeutic options
      include chemotherapy, using either established (e.g. melphalan) or newly
      available (e.g. thalidomide) drugs and high-dose treatment with stem-cell support
      (autologous as well as allogeneic). Recent research has focused on defining the
      target population for the different therapeutic approaches, taking into account
      pre-treatment characteristics of patients, particularly age, and aims to balance
      treatment benefit with potential adverse events. In this review we present the
      data available on the most recent trials dealing with the treatment of elderly MM
      patients.

PMID- 17454587
TI  - Autocrine VEGF loops, signaling pathways, and acute leukemia regulation.
AB  - Data obtained from animal models, and partially confirmed in pre-clinical
      studies, have provided clear evidence of the importance of angiogenesis for the
      growth of solid tumors. Similarly, in hematological cancers such as leukemias and
      lymphomas, the role of angiogenesis has been under intense scrutiny. However, the
      molecular singularities of leukemia, namely its cellular origin, have suggested a
      putative role for angiogenesis in these tumors may have distinct features. We and
      others have shown acute leukemia cells use angiogenic growth factor signaling
      pathways, namely those activated by vascular endothelial growth factor (VEGF) in
      autocrine and paracrine fashion. Autocrine and paracrine VEGF stimulation of
      subsets of leukemias results in cell proliferation, increased survival and
      migration. This review discusses recent advances in the field of leukemia
      angiogenesis, focusing on the role of VEGF and its receptors, acting in a
      paracrine or autocrine manner. We also briefly describe some of the novel anti
      angiogenic compounds, namely VEGF blockers, and suggest their use to treat
      subsets of hematological malignancies may have clinical benefit.

PMID- 17454588
TI  - Acute promyelocytic leukemia: a novel PML/RARalpha fusion that generates a
      frameshift in the RARalpha transcript and ATRA resistance.
AB  - Acute promyelocytic leukemia (APL) is characterized by increased promyelocytes in
      the marrow that harbor a t(15;17) and promyelocyte leukemia (PML)/RARalpha fusion
      gene. The oncogenic gene product is believed to act through disruption of the
      transcription-modulating function of RARalpha. Differentiation of promyelocytes
      and remission is achieved with all transretinoic acid (ATRA) therapy usually in
      combination with chemotherapy. This report describes a patient with the t(15;17)
      who did not respond typically to ATRA and IDAC induction chemotherapy, although
      achieved and remains in complete remission five years following induction and one
      consolidation with high dose cytarabine (HIDAC). RT-PCR and sequencing revealed a
      novel fusion of RARalpha exon 3 to PML exon 5 that creates a frameshift and
      premature stop codon in the RARalpha portion of the transcript. Since none of the
      RARalpha functional domains are maintained, this case highlights the possibility
      that PML/RARalpha may directly affect promyelocyte differentiation through
      disruption of PML function.

PMID- 17454589
TI  - Phase II, randomized, multicenter, comparative study of peginterferon-alpha-2a
      (40 kD) (Pegasys) versus interferon alpha-2a (Roferon-A) in patients with
      treatment-naive, chronic-phase chronic myelogenous leukemia.
AB  - The efficacy and safety of peginterferon-alpha-2a (40 kD) (PEG-IFNalpha-2a), 450
      microg once weekly, versus IFNalpha-2a, 9 MIU once daily, for 12 months, was
      evaluated in a Phase II study in IFN-naive patients with chronic-phase,
      Philadelphia-chromosome-positive CML. At the end of the treatment, complete
      hematological response was observed in 66.2% (47/71) and 45.2% (33/73) of the PEG
      IFNalpha-2a group and IFNalpha-2a groups, respectively (p = 0.009), and major
      cytogenetic response occurred in 35.2% and 17.8%, respectively (p = 0.016). PEG
      IFNalpha-2a was at least as effective as IFNalpha-2a overall, including
      progression-free survival at the end of treatment, and overall survival after 30
      months of follow-up. Adverse events necessitated fewer withdrawals but more dose
      adjustments in the PEG-IFNalpha-2a group compared with the IFNalpha-2a group
      (11%versus 23%, and 84.5%versus 65.8%, respectively). In conclusion, PEG-IFNalpha
      2a (40 kD), 450 microg once weekly, compared with IFNalpha-2a, 9 MIU once daily,
      resulted in higher rates of hematologic and cytogenetic response and greater
      overall survival.

PMID- 17454590
TI  - CD4+ T lymphocyte counts after autologous transplantation in multiple myeloma: a
      retrospective study.
AB  - The risk for opportunistic infections is correlated with low CD4+ T lymphocyte
      counts in patients with HIV. We performed a retrospective analysis in 54 patients
      with multiple myeloma undergoing high-dose melphalan chemotherapy + autologous
      peripheral blood stem cell transplantation to better define the value of routine
      control of CD4+ T lymphocyte counts in this important patient group. In 61% of
      our patients, CD4+ T lymphocyte counts after recovery from neutropenia were
      <200/microl and <100/microl in 24% (median = 181/microl). Overall survival,
      progression-free survival, response to antineoplastic therapy and frequency of
      post-transplant infections were not significantly different when patients with
      CD4+ T lymphocyte counts <200/microl and >200/microl were compared. However,
      overall survival was significantly shorter in the subgroup of 13 patients with
      very low CD4+ T lymphocyte counts (<100/microl) (P = 0.036). In 79.6% of all
      patients, at least one infection NCI-CTC grade II - IV developed within 100 days
      post-transplant. Opportunistic infections were rare. This analysis suggests that
      patients with CD4+ T lymphocyte counts < 100/microl may have a poorer prognosis.

PMID- 17454591
TI  - Development of adapted RECIST criteria to assess response in lymphoma and their
      comparison to the International Workshop Criteria.
AB  - RECIST (response evaluation criteria in solid tumours) uses a unidimensional
      approach to tumour measurement and has been widely adopted for assessing the
      response rate of new therapies in solid tumour clinical trials. For lymphoma, the
      IWC (International Workshop Criteria), based on bidimensional product assessment,
      is generally utilised. We adapted RECIST for use in lymphoma and compared
      responses with the IWC in three Phase II lymphoma trials (n = 115). Measures of
      agreement estimated the concordance between the adapted RECIST and the IWC
      response assessments. A Pearson's coefficient estimated the correlation between
      changes in uni- and bidimensional measurements in a subset of patients (n = 75).
      All measures of agreement were very high [kappa = 0.86 (95% CI: 0.76 - 0.95),
      percent agreement 0.93 (95% CI: 0.87 - 0.97), positive agreement 0.90 (95% CI:
      0.87 - 0.98), negative agreement 0.92 (95% CI: 0.89 - 0.98)]. Pearson's
      coefficient was 0.92 (95% CI: 0.87, 0.95). The lymphoma-adapted RECIST is simpler
      to apply than the IWC and yields near identical response rates. The adapted
      RECIST should be considered for inclusion into any new draft of the IWC.

PMID- 17454592
TI  - Angioimmunoblastic T cell lymphoma: treatment experience with cyclosporine.
AB  - Angioimmunoblastic T cell lymphoma is a distinct entity for which there is no
      standard therapy. On the basis of the rationale that CsA may represent a novel
      drug for AITL, a disease with considerable immune dysregulation, and encouraging
      case reports, the authors have treated 12 patients with this agent. Ten had
      failed prior steroids and/or chemotherapy and two had no prior therapy. CsA was
      administered at a dose of 3 - 5 mg/kg PO bid for 6 - 8 weeks and gradually
      tapered by 50 mg every 1 - 3 weeks. Responding patients received a maintenance
      dose of 50 - 100 mg, with a gradual taper after a maximal response was achieved
      as tolerated. Doses were titrated for renal dysfunction or hypertension. CsA
      levels were not monitored. Eight of 12 patients responded (three complete and
      five partial remissions). Dose reductions were required in six patients; renal
      insufficiency (n = 3), fatigue (n = 2), and hypertension (n = 1). Two patients
      developed acute infections and one patient died shortly after active treatment.
      These results suggest that CsA deserves further testing as a novel therapy for
      AITL. By interrupting T-cell activation, CsA may alter the immune dysregulation
      that characterizes AILT. The efficacy of CsA is being explored in patients with
      recurrent AILT in a prospective trial (ECOG 2402).

PMID- 17454593
TI  - Is the follicular lymphoma international prognostic index better than the
      international prognostic index to identify high-risk follicular lymphoma
      patients?
AB  - The aims of this study are to validate follicular lymphoma international
      prognostic index (FLIPI) prognostic score and to compare it with the
      international prognostic index (IPI) in a cohort of 57 Brazilian patients.
      According to IPI, 24 patients (42%) were in the low-risk, 28 (49%) in the
      intermediate-risk, and 4 (7%) in the high-risk group. The distribution according
      to FLIPI was: 20 (35%) in the low-risk, 8 (14%) in the intermediate-risk, and 29
      (51%) in the high-risk group. According to IPI score, median OS was not reached
      for the low-risk, it was 45 months for the intermediate-risk and 25 months for
      the high-risk group (p < 0.001). When FLIPI score was applied, median OS was not
      reached for the low and intermediate-risk, and was 42 months for the high-risk
      group (p = 0.0064). These findings suggest that: (1) FLIPI score could be
      validated in a Brazilian population; (2) FLIPI is more accurate than IPI to
      identify FL patients having worse prognosis (51%); (3) IPI seems to be a better
      tool for clinical decisions because it selected a smaller high-risk group (7%)
      having worse prognosis. In our opinion, IPI high-risk patients are the real
      candidates for more aggressive therapies, avoiding unnecessary over-treatment.

PMID- 17454594
TI  - HLA associations, microsatellite instability and epigenetic changes in thyroid
      lymphoma in Chinese.
AB  - In Chinese, autoimmune thyroid disease (AITD) is very common but lymphoma of the
      thyroid is a rare disease. Southern Chinese AITD is common in females and is
      strongly linked to the HLA haplotype A2B46DR9. We studied the HLA association,
      aberration p15, p16 and p73 promoter methylation and microsatellite instability
      in Chinese primary thyroid lymphoma patients to elucidate their relationship with
      AITD and the relationship between thyroid diffuse large cell lymphoma (DLCL) and
      marginal zone lymphomas (MZL). Despite a female preponderance (8:1) and the
      finding of cases with histological and immunological evidence of AITD, a
      significant HLA association was not found. MSI was absent, but aberrant promoter
      methylation was found in both thyroid MZL and DLCL and p73 methylation was
      unexpectedly common.

PMID- 17454595
TI  - Two autologous transplants in the treatment of patients with Hodgkin's lymphoma:
      analysis of prognostic factors and comparison with a single procedure.
AB  - We summarized registry data of the long term observation of 35 patients treated
      with two autologous transplants. Prognostic factors for overall survival (OS) and
      DFS were analyzed. The OS was compared with 105 patients from a single transplant
      group. Two factors were significant in univariate analysis of DFS after the
      second transplant: response to the first transplant (complete remission (CR)
      versus progressive disease (PD) p = 0.041) and the disease status at the time of
      the second autologous stem cell transplantation (ASCT) (CR versus partial
      remission (PR) p = 0.004; CR versus PD p = 0.0002). In the multivariate analysis
      only the last of the parameters remain significant (RR 2.30, p = 0.004, 95% CI;
      1.30 - 4.04). In the analysis of OS, two factors were significant in univariate
      analysis: status of the disease at the first transplant (PR versus PD p = 0.008)
      and response to the first transplant (CR versus PD p = 0.025). None of those
      factors remained significant in a multivariate analysis. A probability of 5-year
      survival after the first transplant in patients treated with two transplants was
      83% (95% CI; 70 - 97%). A tendency towards better survival was seen in patients
      treated with two transplants (p = 0.01). The trend toward better survival from
      the time of diagnosis is kept for those who entered CR or PR after standard
      chemotherapy (p = 0.097) but not for the whole group (p = 0.13).

PMID- 17454596
TI  - HLA-DR protein status predicts survival in patients with diffuse large B-cell
      lymphoma treated on the MACOP-B chemotherapy regimen.
AB  - Loss of major histocompatibility class II (MHC class II) molecules on diffuse
      large B-cell lymphoma (DLBCL) has been associated with poor survival; however,
      none of these reports analysed a uniformly treated patient cohort. This study was
      designed to validate one MHC class II antigen, HLA-DR, as a prognostic marker in
      patients uniformly treated with the MACOP-B regimen. Immunostaining results were
      correlated with the international prognostic index (IPI) score and overall
      survival (OS). Of the 97 cases, 82 had interpretable staining. Of these, 52
      expressed HLA-DR (median OS, 16.2 years) while 30 were negative (median OS, 4.2
      years, P = 0.037). The IPI was also predictive of OS in the study group (P =
      0.023). A Cox multivariate model established both IPI (P = 0.031) and HLA-DR (P =
      0.04) as independent predictors of OS. This is the first demonstration of the
      prognostic relevance of HLA-DR in a uniformly treated DLBCL patient group.

PMID- 17454597
TI  - Mucosa associated lymphoid tissue lymphoma of the lung: the Royal Marsden
      Hospital experience.
AB  - Mucosa associated lymphoid tissue (MALT) lymphoma of the lung is a rare disease
      with an indolent clinical behaviour. This single centre retrospective analysis
      evaluates the treatment strategies and clinical outcome for these patients. A
      total number of ten patients (7 male/3 female) were identified between January
      1997 and October 2005 and their records analysed. At diagnosis the patients
      presented with unspecific symptoms (cough, shortness of breath and lower
      respiratory chest infection) which were further evaluated. Six patients had stage
      IAE disease, two patients stage IIAE and in two patients disease was stage IV.
      The initial treatment consisted of surgery alone (3 patients), chemotherapy +/-
      rituximab (5/1 patients), single agent rituximab (1 patient) and wait & watch
      strategy (1 patient). After a median follow-up time of 3.4 years the overall
      survival was 90% at 3 years. In conclusion, our data suggest that most of the
      patients with MALT of the lung had localized disease which generally responded
      well to systemic or local therapy and resulted in favourable long-term outcome
      underlining the indolent course of this disease.

PMID- 17454598
TI  - CODOX-M/IVAC (NCI 89-C-41) in children and adolescents with Burkitt's
      leukemia/lymphoma and large B-cell lymphomas: a 15-year monocentric experience.
AB  - During the last 15 years, we have used the National Cancer Institute (NCI) 89-C
      41 protocol in patients aged younger than 21 years with Burkitt's
      leukemia/lymphoma (BLL) and diffuse large B-cell lymphoma (DLBCL). According to
      the Magrath staging system, patients were classified as low and high risk. Low
      risk received three cycles of the CODOX-M regimen; high-risk patients received
      four alternating cycles with the CODOX-M and IVAC regimens. Thirty-five patients
      entered the study: 32 (91%) achieved complete remission (CR); three were non
      responders and died and one patient died in CR. Two responders relapsed after 2
      months and one presented early B acute lymphoblastic leukemia 33 months from the
      end of therapy. The 5-year overall survival and event free-survival are 83% and
      80%, respectively. No late toxicity was registered. In our experience with a
      median follow-up of 11 years, the NCI 89-C-41 protocol has confirmed its high
      cure rate in BLL and DLBCL children and adolescents.

PMID- 17454599
TI  - Cyclosporin in subcutaneous panniculitis-like T-cell lymphoma.
AB  - Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of
      hematologic malignancy characterized by lesions in subcutaneous fat associated
      with systemic symptoms. The standard treatment of the disease, currently, is not
      established, but CHOP or CHOP-like regimens are usually given. We report, herein,
      4 cases of SPTCL diagnosed by histopathology and immunohistochemistry who were
      refractory to CHOP and/or ESHAP and/or fludarabine-based regimen, but showed
      rapid improvement within weeks after oral cyclosporin 4 mg/kg/day. Three
      sustained complete remission for the durations of 8 - 9 months off-treatments. T
      cell receptor gene rearrangement revealed polyclonality in 3 cases and
      monoclonality in 1 case. Our data suggest the benefit of incorporating
      cyclosporin into the treatment regimen for SPTCL.

PMID- 17454600
TI  - Glutathione-S-transferase genotypes influence prognosis in follicular non
      Hodgkin's Lymphoma.
AB  - Polymorphisms in detoxification enzymes of the glutathione S-transferase (GST)
      family have been associated with risk and prognosis of several cancer types. We
      studied deletions of GSTM1 and GSTT1, and the GSTP1 Ile(105)Val polymorphism in
      89 patients with follicular lymphoma (FL). Patients with a GSTM1 or GSTT1
      deletion had a significantly worse event-free survival, when compared with
      patients with undeleted genotype (p = 0.03 and p = 0.03, respectively). Outcome
      was even worse in patients with a double negative genotype, in comparison with
      patients with only one GST deletion or normal genotype (p = 0.01). In the
      multivariate analysis, the GSTM1/GSTT1 genotype tended to have a prognostic
      significance independent from the Follicular Lymphoma International Prognostic
      Index (FLIPI) score. In particular, GSTM1/T1 deletions identified patients with
      negative prognosis in the low (<3) FLIPI score group (p = 0.01). Larger
      prospective studies including homogeneously treated patients will be needed to
      confirm these results.

PMID- 17454601
TI  - Standard CHOP-21 as first line therapy for elderly patients with Hodgkin's
      lymphoma.
AB  - There is no consensus on the optimal chemotherapy regimen for Hodgkin's lymphoma
      patients > or = 60 years. We present our institution's results of 5 years, using
      CHOP-21 as standard for this patient group. Twenty-nine patients with a median
      age of 71 years (range, 60 - 91) were included in this cohort. Fifty-five percent
      had known co-morbidities. Stage I/IIA patients (38%) were treated with 2 - 4
      cycles of CHOP followed by radiotherapy. Stage IIB - IV patients (62%) received 6
      - 8 cycles of CHOP and for the majority (13/18 pts) no radiotherapy. Two
      treatment-related deaths occurred. Febrile neutropenia was the most common
      toxicity (31%). The complete response rate after CHOP +/- radiotherapy was 93%.
      With a median follow-up of 41 months, five patients have relapsed and four have
      died from Hodgkin's lymphoma. So far, no relapses have occurred after 2 years
      from the end of therapy. Overall survival and progression-free survival at 3
      years were 79% and 76%, respectively. We conclude that CHOP-21 is a well
      tolerated and effective treatment for elderly patients with Hodgkin's lymphoma.

PMID- 17454602
TI  - Lack of an association between Chlamydia psittaci and ocular adnexal lymphoma.
AB  - The objective of this study was to assess whether there is PCR evidence for C.
      psittaci DNA in ocular adnexal lymphoma specimens collected in an academic
      institution in the U.S. This was a retrospective, single-center study of patients
      from 1994 - 2004. We used 28 ocular adnexal lymphoma biopsy specimens from adult
      patients, 16 control lymphoma specimens from patients with systemic lymphomas not
      involving the ocular adnexa, and five control benign adnexal tissue samples. The
      presence of C. psittaci DNA was investigated by polymerase chain reaction (PCR)
      in each group. Two different assays were utilized: (1) conventional PCR/gel based
      assay targeting a 111-bp fragment of the 16S gene and (2) a real-time PCR assay
      amplifying a 148-bp portion of the 16S gene with detection via a specific
      fluorescent probe. Amplification was carried out to 60 cycles. Positive controls
      consisted of isolated DNA from C. psittaci strains VS1, CP3, and FP. A human DNA
      internal control was used to assess sample DNA quality and amplification success.
      Mean outcome measure was the presence of C. psittaci DNA. Using both assays, all
      patient samples in all categories yielded negative results. Both assays detected
      C. psittaci DNA from isolated strains. Internationally, Chlamydia psittaci has
      been associated with ocular adnexal lymphomas with great variability. Similar to
      several other recent studies in the USA, our study could not confirm the presence
      of C. psittaci in ocular adnexal lymphomas. Differences in the prevalence of C.
      psittaci infection in various geographic regions or technical differences in the
      application of the assays may underlie the variability in the association between
      C. psittaci and ocular adnexal lymphoma.

PMID- 17454603
TI  - Angiogenesis in non-Hodgkin's lymphoma: clinico-pathological correlations and
      prognostic significance in specific subtypes.
AB  - The aim of the study was to evaluate angiogenesis in different subtypes of non
      Hodgkin's lymphoma (NHL) and to correlate angiogenic scores to clinical
      endpoints. Pre-therapeutic lymph node biopsies from 308 patients with NHL [107
      follicular B-cell lymphoma (FL), 94 diffuse large B-cell lymphoma (DLBCL), 107
      peripheral T-cell lymphoma (PTCL)] were studied. Microvessels were scored
      according to the Chalkley and microvessel density method (MVD) methods. Vascular
      endothelial growth factor (VEGF) protein expression was evaluated by
      immunohistochemistry. Both Chalkley and MVD methods showed, that the lymphoma
      subtypes differed significantly in angiogenic scores (P < 0.001). Angiogenic
      scores in tumor area were highest in PTCL, and lowest in FL. However, a
      remarkable high microvessel density was found in interfollicular areas of FL. In
      FL, high interfollicular MVD scores predicted progressive disease and poorer
      overall and event-free survival (P = 0.024 and 0.013). High interfollicular
      Chalkley scores correlated with transformation to DLBCL (P = 0.01). VEGF
      expression was detected in all NHL subtype, and the strongest expression was
      found in PTCL. In FL, patients with diffuse VEGF expression in lymphoma cells had
      poorer overall survival than those with focal expression.

PMID- 17454604
TI  - Early therapeutic response assessment by (18)FDG-positron emission tomography
      during chemotherapy in patients with diffuse large B-cell lymphoma: isolated
      residual positivity involving bone is not usually a predictor of subsequent
      treatment failure.
AB  - Residual 2-fluoro-2-deoxyglucose (FDG) - positron emission tomography (PET)
      positivity during treatment of patients with diffuse large B-cell lymphoma
      (DLBLC) prospectively identifies a subgroup at high likelihood of subsequent
      treatment failure. A single institution clinical audit of FDG-PET performance for
      this indication was undertaken for patients with DLBCL treated with anthracycline
      based chemotherapy +/- radiotherapy. Of 45 eligible patients, 14 (31%) were PET
      positive after a median of three chemotherapy cycles (range 1 - 5), of which 10
      (71%) progressed at a median of 6.5 months. An interim positive PET was a
      statistically significant adverse prognostic factor for treatment failure (P <
      0.0001, log-rank analysis) with a hazard ratio for a positive interim-treatment
      PET of 9 (95% confidence interval = 4 - 55) and positive predictive value of 71%
      and negative predictive value of 90%. Notably, four patients with low-grade FDG
      avidity limited to sites previously involved by biopsy-proven osseous lymphoma,
      remain progression-free (median follow-up 62 months). Low-grade FDG-avidity on
      interim restaging at sites of bone involvement by DLBCL at diagnosis, appears to
      be less predictive of disease progression than residual nodal or extra-nodal soft
      tissue abnormality by PET.

PMID- 17454605
TI  - Wilms' tumor gene (WT1) is predominantly expressed in clonal hematopoietic cells
      in myelodysplastic syndromes.
AB  - To determine the expression of Wilms' tumor gene (WT1) in clonal hematopoietic
      cells in patients with myelodysplastic syndromes (MDS), immunochemistry labelling
      (alkaline phosphatase anti-alkaline phosphatase) and fluorescence in situ
      hybridization (FISH) were coperformed on bone marrow cytospins from 18 patients
      whose abnormal karyotypes had been determined by G-binding analysis. Compared to
      12 healthy donors, WT1 positive nucleated cells in MDS marrows were significantly
      higher (t = 2.30; P = 0.032). Moreover, WT1 was expressed predominantly in MDS
      clonal cells (with abnormal FISH signals) rather than in non-clonal cells
      (residual normal cells) (t = 2.19; P = 0.043).

PMID- 17454606
TI  - Inhibition of normal lymphocyte proliferation by Indirubin-3'-monoxime: a
      multifactorial process.
AB  - Indirubin-3'-monoxime (IO) is a derivative of Indirubin, compound of a Chinese
      medicinal recipe used to treat various diseases including leukemia. In this
      study, we investigated to what extent IO inhibits the growth of normal human
      lymphocytes. We defined various experimental conditions of peripheral blood
      lymphocyte treatment: IO introduced (i) on unstimulated lymphocytes, (ii) or on
      stimulated lymphocytes at the time of phytohemagglutinin stimulation (L1
      protocol), (iii) 48 h after the beginning of stimulation (L2 protocol), and (iv)
      after nocodazole synchronization of stimulated lymphocytes. IO induces a
      concentration dependent cytotoxic effect yielding a characteristic sub-G1 peak in
      normal stimulated lymphocytes. Cell death was partly due to necrosis and
      apoptosis. Normal unstimulated lymphocytes remained insensitive to the cytotoxic
      effect of 10 microM IO treatment. A cell cycle inhibition was observed after IO
      treatment, stronger for the L1 than for the L2 protocol, without induction of
      polyploidy after Nocodazole synchronization. These cellular consequences were
      associated with a decrease in CDK activity, and with CDK and cyclin gene
      expression modifications. The inhibition of lymphocyte proliferation by IO
      indicates that indirubin derivatives may be potent immunosuppressive agents.

PMID- 17454607
TI  - Persistent positron emission tomography positivity secondary to benign
      histiocytic proliferation after treatment of Hodgkin lymphoma.

PMID- 17454608
TI  - (18)F-FDG-PET-facilitated diagnosis of lymphoma presenting with fever of unknown
      origin and cold agglutination.

PMID- 17454609
TI  - Rituximab is effective for extensive steroid-refractory chronic graft-vs.-host
      disease.

PMID- 17454610
TI  - DAT-negative hemolytic anemia in a chronic lymphocytic leukemia patient treated
      with alemtuzumab.

PMID- 17454611
TI  - Sudden cardiac failure in a beta-thalassemia major patient receiving chemotherapy
      for acute promyelocytic leukemia.

PMID- 17454612
TI  - Allogeneic stem cell transplantation for hepatosplenic gammadelta T-cell
      lymphoma.

PMID- 17454613
TI  - Severe IgA-mediated autoimmune haemolytic anaemia in Hodgkin lymphoma: a very
      rare event.

PMID- 17454614
TI  - A new allelic discrimination assay using locked nucleic acid-modified nucleotides
      (LNA) probes for detection of JAK2 V617F mutation.

PMID- 17454615
TI  - Development of streptococcus meningitis and Epstein-Barr virus reactivation after
      non-T-cell-depleted human leukocyte antigen-haploidentical peripheral blood stem
      cell transplantation based on feto-maternal microchimerism.

PMID- 17454616
TI  - Multidrug resistance in lymphoma: is it time for clinical trials?

PMID- 17454617
TI  - Angioimmunoblastic T-cell lymphoma: still a dismal prognosis with current
      treatment approaches.

PMID- 17454618
TI  - The elusive search for a viral culprit in non-EBV-associated Hodgkin lymphoma.

PMID- 17454619
TI  - The SUV and FLT PET: a tasty alphabet soup or a dog's breakfast?

PMID- 17454620
TI  - Understanding hairy cell leukemia genetics.

PMID- 17454621
TI  - Denileukin diftitox and vision loss.

PMID- 17454622
TI  - Treatment of the patient with diffuse large B-cell lymphoma with medical co
      morbidities: newer therapies needed.

PMID- 17454623
TI  - Xenograft models for the preclinical evaluation of new therapies in acute
      leukemia.
AB  - Major advances in understanding the pathophysiology of acute leukemia have
      resulted in a dramatic increase in the availability of novel compounds for
      clinical trials. However, since the number of new drugs far exceeds the number of
      clinical trials that can be conducted because of the availability of eligible
      patients, there is an urgent need to utilize reliable preclinical models for the
      prioritization of the most promising potential therapies for those clinical
      trials. The most widely used preclinical models for the acute leukemias are human
      tumor xenografts established in immune-deficient mice, and genetically engineered
      mouse strains. This review summarizes the recent developments and considerations
      in the use of xenograft models of acute lymphoblastic leukemia, acute myeloid
      leukemia, and acute promyelocytic leukemia for the preclinical testing of new
      therapies.

PMID- 17454624
TI  - Gene expression profiling in diffuse large B-cell lymphoma.
AB  - Diffuse Large B cell lymphoma (DLBCL) is characterized by a markedly
      heterogeneous clinical course and response to therapy that is not appreciated
      with standard histopathologic and immunophenotypic evaluations. Analysis of
      global gene expression using DNA microarrays has the potential to improve the
      classification of lymphomas. Molecular profiling may allow the description of
      specific disease subtypes with similar clinical behavior and outcome. In
      addition, gene expression profiling has led to the discovery of new putative
      genes and a better understanding of aberrant signaling pathways. These insights
      may lead to the discovery of new targeted therapies. This review describes the
      progress that has been made in our understanding of DLBCL as a result of gene
      expression profiling.

PMID- 17454625
TI  - Phase I trial of (90)Y-ibritumomab tiuxetan in patients with relapsed B-cell non
      Hodgkin's lymphoma following high-dose chemotherapy and autologous stem cell
      transplantation.
AB  - Between January 2001 and September 2005, 19 patients with progressive B-cell non
      Hodgkin's lymphoma were treated with a cohort-specific dose of yttrium-90
      ibritumomab tiuxetan (0.10 - 0.20 mCi/kg) to determine appropriate dosing in
      patients who had previously received high-dose chemotherapy and autologous stem
      cell transplantation (ASCT). Patients were required to have adequate end organ
      function and bone marrow status. Patients had been treated with a median of three
      prior therapies (range, 1 - 9). The median time from ASCT to radioimmunotherapy
      was 28 months. Hematologic toxicities were dose-limiting and included grade 3 - 4
      thrombocytopenia (53%), neutropenia (32%), and anemia (21%). The majority of
      grade 3 - 4 events occurred at the 0.2 mCi/kg dose level. Nine patients responded
      (complete response, complete response unconfirmed, or partial response) to the
      therapy. At a median follow-up of 37 months, the 1-year event-free and overall
      survival rates were 26% and 57%, respectively. A dose of 0.2 mCi/kg ibritumomab
      tiuxetan is safe and effective for patients with progressive disease after high
      dose chemotherapy and ASCT.

PMID- 17454626
TI  - A weekly regimen with dose escalation of doxorubicin for patients with advanced
      Hodgkin's lymphoma: results of a phase II study of the Groupe d'Etudes des
      Lymphomes de l'Adulte (GELA).
AB  - This multicenter phase II study assessed the feasibility and efficacy of a weekly
      chemotherapy regimen with a moderately escalated dose of doxorubicin administered
      over 16 weeks, followed by radiation therapy (RT) to bulky sites. From July 1996
      to February 1998, 44 untreated patients with stage IIIB-IV Hodgkin's lymphoma
      (HL), and 0 - 2 risk factors described by the Memorial Sloan-Kettering Cancer
      Center, were treated. Chemotherapy was a combination of increased-dose
      doxorubicin with conventional doses of cyclophosphamide, vinblastine, prednisone,
      vindesine, bleomycin, and etoposide. Patients received four cycles of the weekly
      regimen for 16 weeks. Forty-one patients received the planned four cycles of
      chemotherapy, and RT was delivered to 36 patients. The incidence of WHO grade 3 -
      4 neutropenia was 90%. A total of 39 patients achieved a complete remission
      (88.6%). The median follow-up was 95 months. The 7-years freedom from treatment
      failure and overall survival estimates were 57% (95% confidence interval (CI),
      41% - 70%), and 93% (95% CI, 80 - 98%), respectively. The relapse rate was
      related to the short duration of chemotherapy, and the failure to prevent
      relapses with consolidation RT. In this study population the 16-week regimen and
      RT to bulky sites were not sufficient for disease control.

PMID- 17454627
TI  - Comparison of (18)F Flurodeoxyglucose PET with Ga-67 scintigraphy and
      conventional imaging modalities in pediatric lymphoma.
AB  - Flurodeoxyglucose PET (FDG PET) is very useful for staging and restaging adult
      lymphomas. Its effectiveness in childhood lymphomas is less established. To
      evaluate the potential utility of FDG PET in the care of pediatric patients with
      lymphomas, we examined the clinical data and imaging findings of 26 patients, 8 -
      19 years of age (14 HD, 12 NHL) who underwent 55 FDG PET studies. Results were
      compared with CT/MRI and gallium scans. FDG PET provided incremental, clinically
      important information in 21% of HD cases and 33% of NHL cases. It was especially
      useful in distinguishing scar tissue from residual disease at the end of therapy.
      In both HD and NHL, FDG PET had higher sensitivity (94%, 90%) and specificity
      (100%, 88%) than CT/MRI and gallium scanning. These results indicate that FDG PET
      is useful in the management of pediatric lymphomas.

PMID- 17454628
TI  - Phase I/II trial of a P-glycoprotein inhibitor, Zosuquidar.3HCl trihydrochloride
      (LY335979), given orally in combination with the CHOP regimen in patients with
      non-Hodgkin's lymphoma.
AB  - A phase I/II trial was performed to investigate the safety and tolerance of
      zosuquidar.3HCL, a potent inhibitor of P-glycoprotein (P-gp), when administered
      orally alone and in combination with the CHOP regimen in patients with untreated
      non-Hodgkin's lymphoma and to determine whether zosuquidar.3HCL affects
      pharmacokinetics of doxorubicin and vincristine. Doses of CHOP remained constant
      and the doses of zosuquidar.3HCL were increased from 200 to 500 mg per dose. A
      total of 15 patients were treated at three dose levels. A target dose providing
      peak and trough levels compatible with prolonged modulation of P-gp function was
      obtained in patients receiving three doses of 500 mg of zosuquidar.3HCL p.o. At
      this dose level, toxicity was minimal and no enhancement of CHOP-related toxicity
      was observed. Zosuquidar.3HCL did not significantly affect the pharmacokinetics
      of doxorubicin and had moderate effects on the pharmacokinetics of vincristine.
      Zosuquidar.3HCL can be safely administered with CHOP therapy using a 24-h
      schedule.

PMID- 17454629
TI  - Clinical features and treatment outcomes of angioimmunoblastic T-cell lymphoma.
AB  - The objective of this retrospective study was to investigate clinical features
      and treatment outcomes in patients with angioimmunoblastic T-cell lymphoma
      (AITL), data of which were collected over a 15-year period. Sixty-five patients
      diagnosed with AITL were included in the study. About half of the patients
      (46.2%) presented with poor performance status (ECOG > or = 2); 72.3% of patients
      belonged to high intermediate or high-risk of IPI and same proportion belonged to
      Class 2 of PIT (Prognostic index for PTCL-U), and most patients (95.4%) were
      diagnosed at an advanced stage. At diagnosis, 27 patients (41.5%) presented with
      malignant pleural effusion, and 22 patients (33.8%) had skin involvement. Most of
      the initial chemotherapy regimens were anthracycline-based (88.2%). Overall
      response rate to initial chemotherapy was 86.2% (64.7% of complete response,
      21.5% of partial response). The median progression-free survival and overall
      survival of all patients was 7.1 months (95% CI, 2.8 - 11.4) and 15.1 months (95%
      CI, 6.7 - 23.5), respectively. Age, performance status, and PIT scores were
      predictive prognostic factors for survival. In conclusion, although AITLs showed
      a good response to the initial chemotherapy, their response durations were short;
      therefore, chemotherapy for AITL should be modified or intensified as in high
      dose chemotherapy.

PMID- 17454630
TI  - Long-term follow-up study on the role of serum CA-125 as a prognostic factor in
      221 newly diagnosed patients with Hodgkin's lymphoma.
AB  - The present study has explored the possible value of sCA-125 as a prognostic
      factor in Hodgkin's lymphoma (HL). From August 1992 to June 2005 sCA-125 was
      measured at presentation and at the end of the treatments in 221 newly diagnosed
      adult patients with HL. In this study 90/221 (41%) patients showed a value
      greater than the standard upper limit of 35 U/ml, and 79/90 (88%) with an
      abnormal sCA-125 were at an advanced stage of the disease. Patients with elevated
      sCA-125 showed a significant reduction in complete remission (CR) rate (76%vs.
      98%; p < 0.0001). Failure of normalization of sCA-125 during the treatment
      revealed that CR had not been reached. Furthermore, no traces of the glycoprotein
      sCA-125 were found in a series of paraffin-embedded samples coming from 15
      patients of this study. In addition, soluble CA-125 was not detected in
      supernatants coming from four different Hodgkin-derived cell lines. The long-term
      follow-up revealed that the group of patients with sCA-125 lower than 35 U/ml, at
      diagnosis, had an estimated 92% event free survival (EFS) rate and a 94% overall
      survival (OS) rate, while the group of patients with sCA-125 greater than 35 U/ml
      had only a 60% EFS rate (log-rank 33.43, p < 0.0001) and a 70% OS rate (log-rank
      23.52, p < 0.0001). Extranodal disease, severe lymphocytopenia and age proved to
      be the only standard factors that could represent a poor chance to survive. At
      multivariate analysis, high sCA-125, E sites >1 and age were the only independent
      factors producing poor outcomes in terms of CR, EFS and OS. Therefore, we believe
      that sCA-125 is a simple, reliable and reproducible tool, which may improve
      existing prognostic systems.

PMID- 17454631
TI  - Detection of Torque teno virus in Epstein-Barr virus positive and negative lymph
      nodes of patients with Hodgkin lymphoma.
AB  - The age-specific incidence of Hodgkin lymphoma (HL) is bimodal with peaks
      occurring among young adults (15 - 34 years old) and people older than 45 years.
      Epstein-Barr virus (EBV) is associated with only one-third of HL cases. This
      study sought to determine if Torque teno virus (TTV) might be independently
      associated with HL. The presence of EBV was appraised by in situ hybridization
      and immunohistochemistry in lymph node biopsies from 46 patients (3 - 81 years
      old) with HL. TTV DNA was assessed by PCR amplification. EBV was detected in 22
      (48%) patients. TTV DNA was detected in 24/46 (52%) patients, as well as in 12/20
      (60%) control patients with lymphoid unspecific hyperplasia. TTV DNA was not
      significantly more frequent in EBV negative (54%) than in EBV positive (50%)
      nodes. However, it was observed that the group of young adults (15 - 34 years, n
      = 19) showed the lowest EBV frequency (21%) but the highest TTV occurrence (60%).
      This may suggest an involvement of TTV infection in the pathogenesis of HL in
      young adults. Further large population-based studies are required to confirm our
      findings.

PMID- 17454632
TI  - The impact of gender, age and patient selection on prognosis and outcome in
      diffuse large B-cell lymphoma - a population-based study.
AB  - Most studies concerning therapy and prognosis in diffuse large B-cell lymphoma
      (DLBCL) are based on highly selected patient material. To evaluate treatment,
      clinical prognostic factors, and outcome in a population-based cohort, we
      performed a retrospective study comprising 535 de novo DLBCL patients in western
      Sweden, diagnosed between 1995 and 2000. The median age was 73 years. Treatment
      with a curative intent was administered to 376 (70%) patients. The International
      Prognostic Index (IPI) strongly predicted overall (OS) and progression-free (PFS)
      survival, but high age (>68 vs < or = 68 years) had no significant influence on
      response rate (p = 0.86) or PFS (p = 0.14). Male sex had a negative impact on
      both OS (p < 0.001) and PFS (p < 0.001), independent of IPI. In conclusion, a
      considerable proportion of the patients did not receive curative treatment, but
      among those treated, the response and PFS were not influenced by age. As men had
      lower PFS and OS than women, it seems important that gender perspective be taken
      into account in future studies.

PMID- 17454633
TI  - Functional diagnosis of residual lymphomas after radiochemotherapy with positron
      emission tomography comparing FDG- and FLT-PET.
AB  - Positron emission tomography (PET) using 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG)
      is used as a functional imaging technique for the staging and follow-up of
      lymphomas. However, additional information about the tumor proliferation rate
      using 3'-deoxy-3'-[(18)F]fluorothymidine (FLT) may be useful for the assessment
      of prognosis. We enrolled 48 patients with Hodgkin's (n = 15) and non-Hodgkin's
      lymphoma (n = 33) with residual masses >2 cm examined by tracer studies with FDG
      and FLT. The results were related to median overall and progression-free
      survival. In 15 out of 48 patients analysed using FDG, positive results were
      found. Using FLT, 10 out of 48 patients were positive. 33 patients were FDG
      negative. Eight patients were positive both using FDG and FLT. Overall survival
      for patients with a negative PET scan was significantly higher than for patients
      with positive PET, irrespective of the tracer used. FLT alone was able to
      discriminate between patients with long or short overall survival. However, there
      was no statistical significance comparing FDG/FLT negative versus FDG negative
      alone. Although FDG detected more lesions than did FLT, the additional biological
      characterization of tumor tissue with respect to proliferation by FLT might be
      useful by providing complementary information for the identification of
      recurrence. However, the present data show no advantage of combined FDG/FLT
      studies over FDG alone with respect to the prediction of survival.

PMID- 17454634
TI  - Pulsed cyclophosphamide, thalidomide and dexamethasone regimen for previously
      treated patients with multiple myeloma: long term follow up and disease control
      after subsequent treatments.
AB  - There are limited data regarding the long term follow up after thalidomide based
      regimen and the outcome of patients when they progress and they receive further
      treatment. We reassessed our original series of 43 patients with previously
      treated multiple myeloma who had received a pulsed cyclophosphamide, thalidomide,
      dexamethasone (CTD) regimen. Among the 43 patients, 14 did not respond to pulsed
      CTD and 29 (67%) achieved at least a partial response. The median PFS for all
      patients was 10 months. After a median follow up of 24 months (range 1 - 62), the
      3 year PFS is 14% and 3 patients remain off treatment and without progression for
      55+, 55+ and 56+ months respectively. Moreover, 28% of patients who progressed
      after CTD achieved a partial response after subsequent treatment which included
      thalidomide, bortezomib or lenalidomide. The median PFS of these patients was 5
      months and the 1 year PFS was 20%. Furthermore, 31% of patients who had responded
      to CTD and then progressed (CTD sensitive) responded to subsequent treatment. We
      conclude that some patients enjoy long responses after CTD and that several
      patients who progress after CTD may respond to treatment with a novel agent-based
      regimen.

PMID- 17454635
TI  - Reduced intensity conditioning with thiotepa, fludarabine, and melphalan is
      effective in advanced multiple myeloma.
AB  - Fifty-three patients with multiple myeloma (MM) underwent an allogeneic stem cell
      transplant (HSCT) from their HLA identical siblings using a reduced-intensity
      conditioning consisting of thioteopa 5 mg/kg, fludarabine 90 mg/m(2), and
      melphalan 80 mg/m(2). Their median age was 52 years (range 38 - 68) and the
      interval from diagnosis 12 months. Forty-three patients (82%) had advanced
      disease and 33 had previously been treated with high-dose therapy with one (N =
      21), or more (N = 12) autologus transplants. Ten (18%) had their allograft
      programmed after induction chemotherapy. The majority (N = 44) received
      peripheral blood as stem cell source. Acute graft-versus-host disease (GVHD)
      grade II - IV developed in 45%, but grade III - IV in only 5%. Cumulative
      incidence of chronic GVHD was 64%. Sixty-two per cent were in complete remission
      (CR) following transplantation. Transplant-related mortality was 13%. Relapse
      incidence was 32%. With a median follow-up of 22 months, 3-year overall survival
      is 45% and progression free survival (PFS) 37%. The thiotepa, fludarabine, and
      melphalan conditioning regimen can produce remissions in the majority of MM
      patients with a limited transplant mortality rate. When used as first line
      treatment the results of transplantation appear even more encouraging.

PMID- 17454636
TI  - Establishment and characterization of the new splenic marginal zone lymphoma
      derived cell line UCH1 carrying a complex rearrangement involving t(8;14) and
      chromosome 3.
AB  - A new cell line, designated UCH1, was established from a patient with splenic
      marginal zone lymphoma (SMZL). UCH1 cells feature a mature B-cell phenotype,
      characterized by surface IgM +, kappa+, CD5-, CD10-, CD19+ and CD20+. The BCL2
      and BCL6 genes retained their germ-line configurations and overexpression of
      cyclin D1 was not detected. UCH1 cells carry numerical and structural aberrations
      in chromosome 3, but these were too complex to be analyzed with the conventional
      G-banding method. Spectral karyotyping (SKY) and fluorescence in situ
      hybridization analysis clearly demonstrated the presence of a balanced
      translocation between chromosomes 8 and 14 [t(8;14)(q24;q32)] in the complex
      aberrations involving chromosome 3. The results of Southern blot analysis
      supported this finding by showing rearrangement of the c-myc gene in UCH1 cells.
      SKY analysis also identified a translocation involving chromosome band 18q21, to
      which BCL2 and MALT1 genes were assigned, suggesting their implication in the
      development or progression of SMZL.

PMID- 17454637
TI  - Tetra-O-methyl nordihydroguaiaretic acid inhibits growth and induces death of
      leukemia cells independent of Cdc2 and survivin.
AB  - Tetra-O-methyl nordihydroguaiaretic acid (M4N) was shown to induce G2 arrest and
      suppress human xenograft tumor growth by inhibiting Cdc2 and survivin. We
      examined the effect of M4N on leukemia and found that M4N inhibited growth and
      induced cell death in leukemic cell lines and blasts from AML patients. However,
      no significant changes in Cdc2 and survivin levels and G2 arrest were observed.
      Cell death and growth inhibition were dependent neither on XIAP, Bcl-2, and Bcl
      X(L) levels nor on caspase-8. M4N did not promote cell differentiation in HL-60
      cells. Interestingly, significant inhibition of AKT phosphorylation was observed
      in M4N treated OCI-AML3 cells. Collectively, our data showed that M4N inhibited
      cell growth and induced cell death in both leukemic cell lines and AML patient
      sample via a mechanism not mediated by Cdc2 and survivin inhibition and suggested
      that the extrinsic and the mitochondrial apoptotic pathways are not essential.

PMID- 17454638
TI  - Gene-gene interactions in the folate metabolic pathway influence the risk for
      acute lymphoblastic leukemia in children.
AB  - Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Genetic
      polymorphisms in the folate metabolic pathway may contribute to the
      susceptibility to childhood ALL because they affect the DNA synthesis,
      methylation and repair. We analysed common genetic polymorphisms of 5,10
      methylenetetrahydrofolate reductase (MTHFR), thymidylate synthase (TS),
      methionine synthase (MS) and methionine synthase reductase (MTRR) in 68 children
      with ALL and 258 healthy controls to investigate their influence on the risk for
      ALL. No significant differences in frequencies of separate polymorphisms were
      observed between both groups. Combined MTHFR 677CT/TT and MS 2756AG/GG genotypes
      showed a nonsignificant tendency to reduce the risk for ALL 2.24-fold (CI: 0.191 
      1.037, P: 0.061). The risk was significantly reduced in carriers of combined
      MTHFR 677CT/TT, MS 2756AG/GG and MTRR 66AG/GG genotypes (OR: 0.312; CI: 0.107 -
      0.907; P: 0.032). Our results suggest that gene - gene interactions that may
      decrease the methylation capacity might have a protective effect on the risk for
      childhood ALL.

PMID- 17454639
TI  - Bmi-1 over-expression plays a secondary role in chronic myeloid leukemia
      transformation.
AB  - It has been demonstrated that over-expression of Bmi-1 occurs in a variety of
      cancers, including several types of leukemia. This gene plays a key role in the
      self-renewal of stem cells. Leukemic cells lacking Bmi-1 underwent proliferation
      arrest and showed signs of differentiation and apoptosis. These findings led to
      the proposal of Bmi-1 as a potential target for therapeutic intervention in
      cancer. In this study, we investigated the role of Bmi-1 in chronic myeloid
      leukemia (CML). Using qRT-PCR, we demonstrated a significantly increased level of
      Bmi-1 transcript in CML cells. Using array analysis, we determined the
      deregulation of several genes after Bmi-1 silencing. Proapoptotic genes BAD and
      TRADD, and CASP8, p16-INK4, BRCA2, Notch4 and Wnt-8B were elevated. PLK1, SOD1,
      E2F-3, two retinoblastoma binding proteins (RBQ1 and RBBP4) and HDGF were reduced
      after Bmi-1 inhibition. Additionally, we tested the impact of Bmi-1 siRNA on CML
      cell growth; however, there was no apparent change after Bmi-1 suppression.
      Despite the fact that Bmi-1 deregulation occurs in CML and its expression is
      connected to several oncogenic processes, Bmi-1 seems to play a secondary role in
      CML transformation.

PMID- 17454640
TI  - The daunting task of modeling response to imatinib therapy in patients with
      chronic myelogenous leukemia.

PMID- 17454641
TI  - HLA typing and VH gene rearrangement analysis in a family with hairy cell
      leukaemia.

PMID- 17454642
TI  - Vision loss following denileukin diftitox treatment: a case report of possible
      posterior ischemic optic neuropathy.

PMID- 17454643
TI  - Lymphoproliferative clonal origin of AIDS-related non-Hodgkin's lymphoma.

PMID- 17454644
TI  - Interdigitating dendritic cell tumors in two patients exposed to topical
      calcineurin inhibitors.

PMID- 17454645
TI  - Paraneoplastic syndrome: subacute cerebellar degeneration in Hodgkin's disease.

PMID- 17454646
TI  - Prospective study of 18F-FDG PET in pediatric mediastinal lymphoma: a single
      center experience.

PMID- 17454647
TI  - Brucellosis in febrile neutropenia.

PMID- 17454648
TI  - Cardiac tamponade in a patient with chronic lymphocytic leukemia.

PMID- 17454649
TI  - Haemolytic uremic syndrome during induction therapy in an acute promyelocytic
      leukemia patient with aberrant phenotype: a possible manifestation of retinoic
      acid syndrome.

PMID- 17454650
TI  - Bilateral subdural hematoma after hematopoietic stem cell transplantation: a
      diagnosis often overlooked.

PMID- 17454651
TI  - Detection of B- and T-cell-specific gene rearrangements in 13 cell lines and 50
      clinical specimens using the BIOMED-2 and the original InVivoScribe primers.

PMID- 17454652
TI  - Successful umbilical cord blood transplantation using a reduced-intensity
      preparative regimen without total body irradiation and tacrolimus plus
      methotrexate for prophylaxis of graft-versus-host disease in a patient with adult
      T-cell leukemia/lymphoma.

PMID- 17454654
TI  - Voice Activity and Participation Profile (VAPP) in assessing the effects of voice
      disorders on patients' quality of life: validity and reliability of the Finnish
      version of VAPP.
AB  - The Voice Activity and Participation Profile (VAPP) is a self-assessment
      questionnaire describing the limitation of activities and participation of
      individuals with dysphonia. In this study, the validity and reliability of the
      Finnish translation of the VAPP was evaluated using 43 outpatients with various
      functional and organic voice disorders. A control group was formed consisting of
      43 subjects matched according to age, gender, and profession, with normal voices.
      The VAPP was sensitive for voice disorders and items in the questionnaire had
      high internal consistency. The VAPP had a strong correlation with the Voice
      Handicap Index. The results showed that the questionnaire is a valid and reliable
      instrument to measure voice-related quality of life. It also showed that
      limitations in activity and participation levels should be examined separately.

PMID- 17454655
TI  - Prosodic contextualization of minimal responses to yes/no-questions in aphasic
      talk-in-interaction: a descriptive single-case study of a Norwegian aphasic
      speaker.
AB  - The article explores aspects of the role of prosody as a contextualization cue in
      aphasic conversation through auditory and acoustic analysis of an aphasic
      speaker's use of pitch variation in responses to closed yes/no-requests. The
      results reveal two prosodic realizations of 'yes' and 'no' contextualizing
      different kinds of responses: a flat realization with no prolongation and minimal
      pauses, signalling decisiveness, and a realization with movement in pitch,
      prolongation and preceding pauses, signalling indecisiveness. The analysis also
      shows how the aphasic uses a particular realization manipulatively for
      interactional purposes. The study illustrates the vital role that seemingly
      unimportant details play in the co-constructive process of creating meaning in
      interaction. The results indicate an area of competence that seems undisturbed in
      this speaker.

PMID- 17454656
TI  - A comparative study of vocal fundamental frequency in the speech of Japanese and
      American hearing-impaired children.
AB  - The mean fundamental frequency (F(0)) of 10 normal-hearing (NH) and 10 hearing
      impaired (HI) Japanese-speaking children were compared to those of 10 NH and 10
      HI American English-speaking children. Results indicated no difference in F(0)
      between the NH groups; while the Japanese-speaking HI children exhibited a
      significantly higher mean F(0) than English-speaking HI children. The HI Japanese
      speaking children also exhibited significantly higher F(0) values than the NH
      Japanese-speaking children. The influence of a language-specific difference in
      pitch application was assumed to be a contributing factor to the F(0) differences
      between the HI groups.

PMID- 17454657
TI  - Assessment of pragmatic language impairment in children referred to psychiatric
      services: a pilot study of the Children's Communication Checklist in a Norwegian
      sample.
AB  - The aim of the present pilot study was to explore whether pragmatic language
      impairments are more prevalent among children referred to child psychiatric
      services (n=21) than among a comparison group of typically developing children
      (n=29) in the age range 8-10 years. A second and minor aim was also to assess the
      usability of a Norwegian translation of the Children's Communication Checklist
      (CCC). Communication disorders defined as a pragmatic score equal to or below 140
      on the CCC were identified in a majority (0.57) of the children in the clinical
      group; the corresponding proportion for the typically developing comparison group
      was only 0.10. Thus, the Norwegian version of the CCC distinguishes between
      children with symptoms of pragmatic language impairments and those with no
      symptoms, as does the English version.

PMID- 17454658
TI  - Perceptual and acoustic analysis of speech in individuals with spinocerebellar
      ataxia (SCA).
AB  - With current progress in genetic research, autosomal, dominant, hereditary,
      neurodegenerative diseases, affecting the cerebellum and cerebellar connections,
      are increasingly diagnosed as spinocerebellar ataxias (SCA). In the present study
      speech samples from 21 subjects with spinocerebellar ataxia (SCA), and 21 matched
      control subjects were analyzed using perceptual and acoustic methodology.
      Dysarthria assessment showed that subjects had mild or mild-moderate dysarthria.
      Perceptual analysis indicated that equalized stress, imprecise consonants, vocal
      instability, monotony and reduced speech rate were the speech parameters that
      yielded the highest mean perceptual ratings. A factor analysis of perceptual
      speech parameters revealed two main factors: Factor 1 was associated with
      articulatory timing and Factor 2 with vocal quality. Acoustic analysis revealed
      significantly reduced speech rate during text reading, reduced alternating and
      sequential motion rates (AMR/SMR), significantly longer and more variable
      syllable and pause durations, and significantly higher vocal instability for
      subjects with SCA compared to control subjects.

PMID- 17454659
TI  - Occupational voice disorders: Is there a firm case for industrial injuries
      disablement benefit?

PMID- 17454660
TI  - Autobiographical memory and emotional disorder: a special issue of Memory.

PMID- 17454661
TI  - Autobiographical memory for trauma: update on four controversies.
AB  - Empirical research since the year 2000 on trauma and autobiographical memory in
      adults is reviewed and related to four enduring controversies in the field:
      Whether traumatic memories are inherently different from other types of
      autobiographical memory; whether memory for trauma is better or worse than memory
      for non-traumatic events; whether traumas can be forgotten and then recalled
      later in life; and whether special mechanisms such as repression or dissociation
      are required to account for any such forgetting. The review concludes that trauma
      and non-trauma memories differ substantially, but only in clinical and not in
      healthy populations. Whereas involuntary memory is enhanced in clinical
      populations, voluntary memory is likely to be fragmented, disorganised, and
      incomplete. Progress in experimental and neuroimaging research will depend on
      analysing how task performance is affected by the interaction of voluntary and
      involuntary memory and by individual tendencies to respond to trauma with
      increased arousal versus dissociation.

PMID- 17454662
TI  - Intrusive memories and rumination in patients with post-traumatic stress
      disorder: a phenomenological comparison.
AB  - The aim of the study was to investigate the phenomenological differences between
      intrusive memories and rumination in PTSD. The study population consisted of 31
      patients with PTSD referred for cognitive behavioural therapy to specialist
      services. A semi-structured interview was used to examine the characteristics of
      the most prominent intrusive memory and rumination. Intrusive memories were
      predominantly sensory experiences of short duration, whereas rumination was
      predominantly a thought process of longer duration. Shame was associated more
      with rumination than with intrusive memories. Anxiety, helplessness, numbness,
      and threat were greater at the time of the trauma than when experiencing the
      intrusive memory. In contrast, feelings like anger and sadness were greater when
      experiencing intrusive memories than at the time of the event. The distinction
      between intrusive memories and rumination is of clinical importance as intrusive
      memories usually decrease with imaginal reliving of the trauma, whereas
      rumination may require different therapeutic strategies, such as rumination
      focused or mindfulness-based cognitive therapy.

PMID- 17454663
TI  - Telling and the remembered self: linguistic differences in memories for
      previously disclosed and previously undisclosed events.
AB  - Prior work suggests that disclosing experiences may provide people with more
      distance, more positive emotion, greater cognitive elaboration, and greater
      certainty regarding those experiences. Two studies (n=58 undergraduates and n=123
      community-living adults) examined linguistic indicators of such differences
      between previously disclosed and previously undisclosed memories elicited on
      subsequent, solitary occasions using the LIWC text analysis program (Pennebaker &
      Francis, 1999). Disclosure was associated with differences in the linguistic
      features of subsequent memories. Potential mechanisms and implications of those
      differences are discussed.

PMID- 17454664
TI  - The Trauma Memory Quality Questionnaire: preliminary development and validation
      of a measure of trauma memory characteristics for children and adolescents.
AB  - It has been suggested that post-traumatic stress is related to the nature of an
      individual's trauma memories. While this hypothesis has received support in
      adults, few studies have examined this in children and adolescents. This article
      describes the development and validation of a measure of the nature of children's
      trauma memories, the Trauma Memory Quality Questionnaire (TMQQ), that might test
      this hypothesis and be of clinical use. The measure was standardised in two
      samples, a cross-sectional sample of non-clinic referred secondary school pupils
      (n=254), and a sample participating in a prospective study of children and
      adolescents who had attended a hospital Accident and Emergency department
      following an assault or a road traffic accident (n=106). The TMQQ was found to
      possess good internal consistency, criterion validity, and construct validity,
      but test-retest reliability has yet to be established.

PMID- 17454665
TI  - Betrayal trauma theory: a critical appraisal.
AB  - Freyd's (1996) betrayal trauma theory holds that children sexually abused by
      their caretakers are prone to develop amnesia for their abuse because awareness
      of abuse would imperil the survival of victims by disrupting their attachment to
      caretakers on whom they depend for food, shelter, and clothing. The purpose of
      this article is to provide an empirical and conceptual critique of betrayal
      trauma theory. Data from studies adduced as supporting the theory have usually
      been open to alternative interpretations, whereas other studies have failed to
      provide any support for the theory. Moreover, there is no convincing evidence
      that children are incapable of remembering their abuse--develop genuine amnesia
      for it--shortly after their molestation. Also, even if children abused by
      caretakers fear disruption of their attachment to the offender, there is no
      reason to assume that they must develop amnesia for their abuse; they can
      maintain the relationship merely by failing to disclose their abuse. Finally, a
      more parsimonious explanation for why some adults may fail to think about their
      abuse until many years later is provided.

PMID- 17454667
TI  - Cue self-relevance affects autobiographical memory specificity in individuals
      with a history of major depression.
AB  - Previously depressed and never-depressed individuals identified personal
      characteristics (self-guides) defining their ideal, ought, and feared selves. One
      week later they completed the autobiographical memory test (AMT). For each
      participant the number of AMT cues that reflected self-guide content was
      determined to produce an index of AMT cue self-relevance. Individuals who had
      never been depressed showed no significant relationship between cue self
      relevance and specificity. In contrast, in previously depressed participants
      there was a highly significant negative correlation between cue self-relevance
      and specificity--the greater the number of AMT cues that reflected self-guide
      content, the fewer specific memories participants recalled. It is suggested that
      in individuals with a history of depression, cues reflecting self-guide content
      are more likely to prompt a shift to processing of information within the long
      term self (Conway, Singer, & Tagini, 2004), increasing the likelihood that self
      related semantic information will be provided in response to cues on the
      autobiographical memory test.

PMID- 17454668
TI  - The endorsement of dysfunctional attitudes is associated with an impaired
      retrieval of specific autobiographical memories in response to matching cues.
AB  - Two studies investigated a hypothesis of Dalgleish et al. (2003) that overgeneral
      memory may arise from matching between task cues and dysfunctional attitudes or
      schemas. In the first study, 111 euthymic patients with at least two previous
      major depressive episodes completed the Dysfunctional Attitude Scale: Form A (DAS
      A) and the Autobiographical Memory Test (AMT). In the second study, 82 patients
      with a borderline personality disorder completed the Young Schema Questionnaire
      (YSQ) and the same version of the AMT. In both studies, patients retrieved less
      specific autobiographical memories in response to cue words that matched highly
      endorsed attitudes or schemas. These results suggest that an impaired retrieval
      of specific memories may be the result of certain cues activating generic, higher
      order mental representations.

PMID- 17454669
TI  - Overgeneral memory and suppression of trauma memories in post-traumatic stress
      disorder.
AB  - The study investigated the relationship between the suppression of trauma
      memories and overgeneral memory in 42 assault survivors with and without PTSD.
      Overgeneral memory (OGM) was assessed with a standard autobiographical memory
      test (AMT). Participants completed two further AMTs under the instructions to
      either suppress or not suppress assault memories, in counterbalanced order.
      Participants with PTSD retrieved fewer and more general memories when following
      the suppression instruction than participants without PTSD, but not under the
      control instruction. OGM correlated with PTSD symptom severity, and measures of
      cognitive avoidance. The results are discussed with reference to current theories
      of overgeneral memory and its possible relationship with PTSD.

PMID- 17454670
TI  - Noninvasive measure of microvascular nitric oxide function in humans using very
      low-frequency cutaneous laser Doppler flow spectra.
AB  - OBJECTIVE: While higher frequency oscillations (0.021-0.6 Hz) in cutaneous blood
      flow measured by laser Doppler flowmetry (LDF) relate to oscillations in blood
      pressure and sympathetic nerve activity, very low-frequency oscillations (VLF,
      0.0095-0.021 Hz) do not. The authors investigated whether VLF LDF power is nitric
      oxide (NO) specific. METHODS: LDF combined with intradermal microdialysis was
      used in the calves of 22 healthy volunteers aged 19-27 years. LDF power spectral
      analysis was performed by windowed fast Fourier transform. The authors tested
      whether the NO synthesis inhibitor nitro-l-arginine (NLA) produced selective
      decreases in VLF power before and after stimulation with acetylcholine. RESULTS:
      NLA alone did not alter total power but selectively reduced VLF power by
      approximately 50%. LDF and spectral power increased markedly across all spectra
      with acetylcholine. This increase was blunted by NLA, which selectively reduced
      VLF power by approximately 50%. CONCLUSIONS: The data suggest that VLF
      oscillations in the laser Doppler signal are NO dependent, increase with
      cholinergic stimulation, and have potential as a noninvasive marker for NO
      dependent microvascular reactivity.

PMID- 17454671
TI  - Computational network model prediction of hemodynamic alterations due to
      arteriolar remodeling in interval sprint trained skeletal muscle.
AB  - OBJECTIVES: Exercise training is known to enhance skeletal muscle blood flow
      capacity, with high-intensity interval sprint training (IST) primarily affecting
      muscles with a high proportion of fast twitch glycolytic fibers. The objective of
      this study was to determine the relative contributions of new arteriole formation
      and lumenal arteriolar remodeling to enhanced flow capacity and the impact of
      these adaptations on local microvascular hemodynamics deep within the muscle.
      METHODS: The authors studied arteriolar adaptation in the white/mixed-fiber
      portion of gastrocnemius muscles of IST (6 bouts of running/day; 2.5 min/bout; 60
      m/min speed; 15% grade; 4.5 min rest between bouts; 5 training days/wk; 10 wks
      total) and sedentary (SED) control rats using whole-muscle Microfil casts.
      Dimensional and topological data were then used to construct a series of
      computational hemodynamic network models that incorporated physiological red
      blood cell distributions and hematocrit and diameter dependent apparent
      viscosities. RESULTS: In comparison to SED controls, IST elicited a significant
      increase in arterioles/order in the 3A through 6A generations. Predicted IST and
      SED flows through the 2A generation agreed closely with in vivo measurements made
      in a previous study, illustrating the accuracy of the model. IST shifted the bulk
      of the pressure drop across the network from the 3As to the 4As and 5As, and flow
      capacity increased from 0.7 mL/min in SED to 1.5 mL/min in IST when a driving
      pressure of 80 mmHg was applied. CONCLUSIONS: The primary adaptation to IST is an
      increase in arterioles in the 3A through 6A generations, which, in turn, creates
      an approximate doubling of flow capacity and a deeper penetration of high
      pressure into the arteriolar network.

PMID- 17454672
TI  - Both ADP and thrombin regulate arteriolar thrombus stabilization and
      embolization, but are not involved in initial hemostasis as induced by
      micropuncture.
AB  - OBJECTIVE: Thrombosis and embolization are main causes of morbidity and
      mortality. Up to now, the relative importance of mediators involved is only
      partly known. It was the aim of this study to investigate the involvement of ADP
      and thrombin in subsequent phases of arteriolar hemostasis and thromboembolism in
      vivo. METHODS: Rabbit mesenteric arterioles were punctured, which induced
      bleeding, hemostasis, and subsequent thromboembolism. This reaction as well as
      the activation state of platelets involved ([Ca(2+)](i)), was monitored in real
      time by intravital (fluorescence) microscopy. RESULTS: Neither inhibition of
      thrombin formation or thrombin activity nor blockade of platelet ADP receptors
      P2Y(1) and P2Y(12) influenced the initial hemostatic reaction: in all experiments
      initial bleeding was stopped by a primary thrombus within 2-3 s. On the other
      hand, both thrombin inhibition and P2Y(1) blockade increased rebleeding
      frequency, which indicates reduced thrombus stability in the long term. Finally,
      inhibition of either thrombin or ADP (via both receptors) reduced aggregate
      formation during the embolization phase by at least 90%. While most participating
      platelets exhibited a transient increase in [Ca(2+)](i) during embolization, an
      increased percentage of platelets showed no calcium response at all during P2Y(1)
      blockade, which was accompanied by reduced platelet-platelet interaction
      strength. CONCLUSIONS: Whereas thrombin and ADP are not involved in the initial
      hemostatic reaction, both substances appear to be essential to prevent
      rebleedings in the long term. During subsequent embolization, ADP (via both
      receptors) and small amounts of thrombin are involved in platelet activation.

PMID- 17454673
TI  - An imaging spectroscopy approach for measurement of oxygen saturation and
      hematocrit during intravital microscopy.
AB  - OBJECTIVE: Oxygen supply and partial pressure are key determinants of tissue
      metabolic status and are also regulators of vascular function including
      production of reactive oxygen species, vascular remodeling, and angiogenesis. The
      objective of this study was to develop an approach for the determination of
      oxygen saturation and hematocrit for individual microvessels in trans- and epi
      illumination intravital microscopy. METHODS: A spectral approach was used, taking
      advantage of the availability of commercial imaging systems that allow digital
      recording of intravital images at a number of predetermined wavelengths within a
      relatively short time. The dependence of validity and precision of saturation
      measurements on critical experimental variables (reference spectra, number and
      selection of wavelengths, exposure time, analysis area, analysis model) was
      evaluated. In addition, a software approach for two-dimensional analysis of
      images was developed. RESULTS: Exposure times per wavelength of about 200 ms and
      use of up to 50 wavelengths evenly spaced from 500 to 598 nm allow automatic
      discrimination of microvessels from tissue background (segmentation) with
      reliable determination of oxygen saturation (in trans- and epi-illumination) and
      hematocrit (in transillumination). CONCLUSIONS: The present imaging spectroscopy
      approach allows detailed assessment of oxygen transport and other functional
      parameters at the microcirculatory level.

PMID- 17454674
TI  - Hypertonic saline and the cerebral microcirculation in obese septic mice.
AB  - OBJECTIVES: Increased morbidity and mortality in critically ill obese patients
      may result from an exaggerated inflammatory response and/or a diminished
      effectiveness of routine therapeutic strategies used in the critical care
      setting. The objectives of this study were to compare the effectiveness of
      hypertonic saline (HTS) resuscitation in obese and lean mice with sepsis and to
      address potential mechanisms underlying HTS-mediated protection against the
      inflammatory and microvascular responses to sepsis. METHODS: Intravital
      videomicroscopy was used to monitor and quantify the adhesion of platelets and
      leukocytes in the brain microcirculation of WT (C57 Bl/6) and ob/ob (B6.V
      Lepob/J) mice subjected to cecal ligation and puncture (CLP) and resuscitated
      with either normal saline or HTS. The dual radiolabeled monoclonal antibody
      method was used to measure P-selectin expression in the microcirculation, while
      the sepsis-induced behavioral deficit was quantified using a multicompartment
      chamber test. RESULTS: HTS attenuated the accumulation of adherent leukocytes and
      platelets and the behavioral deficit observed at 4 h after CLP in both WT and
      ob/ob mice. CLP-induced upregulation of P-selectin in the brain microcirculation
      was attenuated by HTS in ob/ob, but not in lean, mice. CONCLUSION: HTS exerts
      significant anti-inflammatory and anti-thrombogenic actions in obese septic mice.
      These responses may be related to the inhibitory effect of HTS on sepsis-induced
      P-selectin expression.

PMID- 17454675
TI  - Impairment of myocardial angiogenic response in the absence of osteopontin.
AB  - OBJECTIVE: Osteopontin (OPN), increased in the heart following myocardial
      infarction (MI), plays an important role in post-MI remodeling. Angiogenesis, an
      important feature of tissue repair, begins in the infarcted myocardium within 3
      days post-MI. Here, the authors studied the role of OPN in myocardial
      angiogenesis using wild-type (WT) and OPN knockout (KO) mice. RESULTS:
      Measurement of angiogenic response using Griffonia simplicifolia lectin-1 (GSL-1)
      staining indicated reduced capillary density in the infarcted region of the OPN
      KO hearts as compared to WT hearts 7 and 14 days post-MI. Arteriolar density was
      lower in OPN KO hearts 14 days post-MI. The number of CD31 positive cells was
      also lower in the infarcted region of the OPN KO hearts as compared to WT hearts
      14 days post-MI. In contrast, capillary and arteriolar densities in the
      noninfarcted regions of OPN KO and WT hearts were not significantly different. In
      vivo myocardial angiogenesis measured using Matrigel implantation in the left
      ventricular myocardium indicated significant decrease in the percentage of vessel
      like areas in the OPN KO vs. WT hearts. Furthermore, in vitro Matrigel tube
      formation assay demonstrated a significant decrease in total tube length in
      cardiac microvascular endothelial cells (CMECs) isolated from OPN KO hearts as
      compared to CMECs from WT hearts. Treatment of OPN KO CMECs with purified OPN
      protein significantly increased total tube length, while bovine serum albumin had
      no effect. CONCLUSION: Lack of OPN impairs myocardial angiogenic response,
      leading to adverse remodeling post-MI.

PMID- 17454676
TI  - Effects of intratumoral injection of CCL2 on monocyte-endothelial cell
      interactions in mouse pancreatic cancer.
AB  - OBJECTIVE: Although monocyte infiltration is an important aspect of the host
      response to tumor growth, the mechanisms of recruitment and their impact on tumor
      growth are still unknown. The authors studied monocyte-endothelial interaction
      and the effect of chemokine CCL2 in orthotopic mouse pancreatic cancer. METHODS:
      The rolling and adhesion of labeled monocytes in peritumoral and intratumoral
      areas were assessed by using an intravital microscope. Further, the effects of
      intratumoral injection or superfusion of CCL2 on in situ recruitment of monocytes
      and other immune cells and adhesion molecules were investigated. RESULTS: More
      monocytes were recruited in the peritumoral area than in the intratumoral area
      with increased vascular interaction, and the effect was more apparent by
      intratumoral CCL2 injection than superfusion. In both CCL2-treated groups
      infiltration of CD11b(+), CD68(+), and CD4(+) cells were increased, but the
      magnitude of increase was larger in intratumoral injection. Quantitative RT-PCR
      for the tumor tissue revealed that ICAM-1 expression was increased by the
      injection of CCL2. CONCLUSION: These results show intratumoral injection of CCL2
      induces effective interaction between monocytes and endothelial cells in the
      peritumoral area of pancreatic cancer accompanied by the upregulation of ICAM-1
      and may possibly become a tool for immunotherapy by promoting the infiltration of
      immune cells in cancers.

PMID- 17454677
TI  - EphB4 expression along adult rat microvascular networks: EphB4 is more than a
      venous specific marker.
AB  - OBJECTIVE: EphrinB2 and EphB4 are considered to be markers of arterial/venous
      identity during embryonic development. However, the expression patterns of these
      arterial/venous-specific markers in adult microvascular networks remain unclear.
      The objective of this study was to characterize the cellular distribution of
      EphB4 expression along the hierarchy of unstimulated and remodeling adult rat
      mesenteric microvascular networks. METHODS: Mesenteric tissue was harvested from
      unstimulated and stimulated adult male Fisher rats, and stained for various
      combinations of EphB4, SM alpha -actin, NG2, and isolectin/CD-31. The
      distribution of EphB4 expression was compared to the cell-specific markers along
      arteriole, venule, and capillary segments for each mesenteric microvascular
      network (n = 32). Arterial/venous expression was also characterized in
      subcutaneous tissue and spinotrapezius muscle. RESULTS: Endothelial cells along
      both venules and arterioles stained positive for EphB4. EphB4 expression levels
      along capillaries correlated with capillary type, as the fluorescence staining
      intensity along capillary sprouts was significantly elevated in comparison to
      capillaries connecting arterioles and venules (mean intensity index = 25 for
      capillary sprouts; 6 for connected capillaries) CONCLUSION: The results suggest
      that EphB4 is not an arterial/venous-specific marker in adult rat microvascular
      networks, and provide new data suggesting that its elevated expression in
      capillaries is indicative of capillary sprouting.

PMID- 17454680
TI  - Evolution of visually guided behavior in artificial agents.
AB  - Recent work on brightness, color, and form has suggested that human visual
      percepts represent the probable sources of retinal images rather than stimulus
      features as such. Here we investigate the plausibility of this empirical concept
      of vision by allowing autonomous agents to evolve in virtual environments based
      solely on the relative success of their behavior. The responses of evolved agents
      to visual stimuli indicate that fitness improves as the neural network control
      systems gradually incorporate the statistical relationship between projected
      images and behavior appropriate to the sources of the inherently ambiguous
      images. These results: (1) demonstrate the merits of a wholly empirical strategy
      of animal vision as a means of contending with the inverse optics problem; (2)
      argue that the information incorporated into biological visual processing
      circuitry is the relationship between images and their probable sources; and (3)
      suggest why human percepts do not map neatly onto physical reality.

PMID- 17454681
TI  - Time and space are complementary encoding dimensions in the moth antennal lobe.
AB  - The contribution of time to the encoding of information by the nervous system is
      still controversial. The olfactory system is one of the standard preparations
      where this issue is empirically investigated. For instance, output neurons of the
      antennal lobe or the olfactory bulb display odor stimulus induced temporal
      modulations of their firing rate at a scale of hundreds of milliseconds. The role
      of these temporal patterns in the encoding of odor stimuli, however, is not yet
      known. Here, we use optical imaging of the projection neurons of the moth
      antennal lobe to address this question. First, we present a biophysically derived
      model that provides an accurate description of the calcium response of projection
      neurons. On the basis of this model, we subsequently show that the calcium
      response of the projection neurons displays a stimulus specific temporal
      structure. Finally, we demonstrate that an encoding scheme that includes this
      temporal information boosts classification performance by 60% as compared to a
      purely spatial encoding. Although the putative role of combinatorial spatio
      temporal encoding strategies has been the subject of debate, our results for the
      first time establish quantitatively that such an encoding strategy is used by the
      insect brain.

PMID- 17454682
TI  - Randomness and variability of the neuronal activity described by the Ornstein
      Uhlenbeck model.
AB  - Normalized entropy as a measure of randomness is explored. It is employed to
      characterize those properties of neuronal firing that cannot be described by the
      first two statistical moments. We analyze randomness of firing of the Ornstein
      Uhlenbeck (OU) neuronal model with respect either to the variability of
      interspike intervals (coefficient of variation) or the model parameters. A new
      form of the Siegert's equation for first-passage time of the OU process is given.
      The parametric space of the model is divided into two parts (sub-and supra
      threshold) depending upon the neuron activity in the absence of noise. In the
      supra-threshold regime there are many similarities of the model with the Wiener
      process model. The sub-threshold behavior differs qualitatively both from the
      Wiener model and from the supra-threshold regime. For very low input the firing
      regularity increases (due to increase of noise) cannot be observed by employing
      the entropy, while it is clearly observable by employing the coefficient of
      variation. Finally, we introduce and quantify the converse effect of firing
      regularity decrease by employing the normalized entropy.

PMID- 17454683
TI  - On a peculiar environmental dependency syndrome in a case with frontal-temporal
      damage: Zelig-like syndrome.
AB  - We report on the case of a patient with frontal-temporal damage from cerebral
      hypoxia, affected by amnesic disturbances and behaviour disorder, who presented a
      peculiar phenomenon of environmental dependency. He assumed a different social
      role in keeping with different environmental circumstances by interpreting a
      character corresponding to the particular context. Three experiments were carried
      out in which the environmental variables were manipulated to verify the
      phenomenon in controlled conditions, and an investigation was conducted during
      the patient's spontaneous manifestations. The phenomenon was interpreted as a
      loss of frontal inhibition whose function was the control of his own identity and
      consequent "attraction" towards a social role proposed by the environment.

PMID- 17454684
TI  - Self-enhancing confabulation: revisiting the motivational hypothesis.
AB  - We report a patient who developed spontaneous confabulation following surgical
      clipping of an anterior communicating artery aneurysm. An autobiographical memory
      test was used to measure the emotional valence of the patient's self
      representations in true and false memories. We found that his confabulations
      included significantly more positive self-representations than his true memories
      and that the overall valence of his confabulations was more positive than that of
      his true memories and than that of the memories of five healthy control
      participants of the same age and educational attainment. It is proposed that
      while cognitive dysfunction may explain how confabulations are formed, emotional
      factors may explain which specific confabulations are constructed.

PMID- 17454685
TI  - Brain activation during working memory after traumatic brain injury in children.
AB  - Eight children with moderate to severe traumatic brain injury (TBI) and eight
      matched, uninjured control children underwent fMRI during an N-back task to test
      effects of TBI on working memory performance and brain activation. Two patterns
      in the TBI group were observed. Patients whose criterion performance was reached
      at lower memory loads than control children demonstrated less extensive frontal
      and extrafrontal brain activation than controls. Patients who performed the same,
      highest (3-back) memory load as controls demonstrated more frontal and
      extrafrontal activation than controls. Our findings of performance and brain
      activation changes in children after TBI await longitudinal investigation.

PMID- 17454686
TI  - Patients with chronic focal cerebellar lesions show no cognitive abnormalities in
      a bedside test.
AB  - The aim of the present study was to show whether cognitive deficits are present
      in chronic cerebellar patients using a self-developed, validated bedside
      screening test. Twenty-one adults with a history of infarction within the
      territory of the posterior-inferior (PICA) or the superior cerebellar artery
      (SCA), and 25 age-, sex-, and education-matched healthy controls participated.
      Lesion localization was based on individual 3D MRI scans. The test took 10-12 min
      including subtests of naming, executive functions, attention, figural and verbal
      memory, reading, long-term memory, mental arithmetic, higher order motor control,
      and spatial functions. Though individual patients tended to make more errors than
      controls, neither total error score nor subscores revealed significant group
      differences. No obvious cognitive deficits appeared to be present in chronic
      cerebellar patients as assessed by a bedside screening test.

PMID- 17454687
TI  - A left attentional bias in chronic neglect: a case study using temporal order
      judgments.
AB  - Previous studies of left visuospatial neglect using temporal order judgments
      (TOJs) have reported a temporal advantage for a stimulus presented on the right
      of fixation. The present case study examines an individual who shows a left
      temporal advantage on TOJ tasks, despite classic left-sided neglect on other
      tasks and in self-report. Experiment 1 found a continued left advantage on TOJs
      when employing a novel red/blue TOJ task to reduce potential response bias.
      Phasic alerting tones presented prior to random trials in Experiment 2 did not
      improve the abnormal attentional bias, as has been reported in previous studies
      of neglect. The addition of unilateral trials mixed within bilateral trials in
      Experiment 3 reduced the observed left advantage, suggesting a flexible
      attentional focus and implicating a role for strategic endogenous attentional
      strategies in this individual. Some implications for our understanding of
      endogenous orienting and relevance to rehabilitation therapy are discussed.

PMID- 17454688
TI  - The ability to pun may be retained in Alzheimer disease.
AB  - Although the deficits and difficulties of the patient with Alzheimer disease (AD)
      are well documented and discussed, less attention is paid to describing some of
      the interesting and unusual abilities that these patients can possess. This case
      report describes an 81-year-old female with moderately severe Alzheimer disease
      who, in spite of some severe cognitive deficits, is able to express impressive
      humor through the extensive use of puns. Acknowledging and focusing on the
      remaining positive attributes of a person with AD can be helpful to both family
      members and professionals.

PMID- 17454690
TI  - Awareness typologies, long-term emotional adjustment and psychosocial outcomes
      following acquired brain injury.
AB  - Previous research suggests considerable heterogeneity within groups of
      individuals identified as having low self-awareness or good self-awareness
      following acquired brain injury (ABI). The present study aimed to identify
      typologies of individuals according to neuropsychological and psychological
      factors related to awareness deficits and compare emotional adjustment and
      psychosocial outcomes at the initial assessment and 12-month follow-up. Eighty
      four participants with ABI (mean time since injury = 3.9 years) were assessed on
      the Self-Awareness of Deficits Interview, Awareness Questionnaire, Symptom
      Expectancy Checklist, Marlowe-Crowne Social Desirability Scale, Hospital Anxiety
      Depression Scale, Sydney Psychosocial Reintegration Scale, and an error self
      regulation index. A 12-month follow-up assessment of emotional adjustment and
      psychosocial outcomes was conducted. A hierarchical cluster analysis
      distinguished four awareness typologies, namely, "poor self-awareness" (n = 12),
      "high defensiveness" (n = 13), "high symptom reporting" (n = 15), and "good self
      awareness" (n = 44). An overall comparison of outcomes indicated that the poor
      self-awareness and high symptom reporting typologies experienced poorer outcomes
      than the high defensiveness and good self-awareness typologies. The findings
      confirm that there are different awareness typologies and highlight the need to
      tailor interventions according to the nature of awareness deficits.

PMID- 17454691
TI  - Awareness of disability after acquired brain injury and the family context.
AB  - The dimension of family context for awareness of disability following acquired
      brain injury (ABI) is examined through a qualitative discourse analysis. Three
      participants with ABI, who were identified by clinicians and relatives as
      demonstrating difficulties with awareness of disability, and three relatives were
      interviewed. The findings highlight important contextual parameters influencing
      the emergence of families' accounts for disability after ABI: (1) availability of
      sense-making resources and use of pre-injury meanings, and (2) incongruity within
      family sense-making and resultant orientating, disputing and contesting of
      accounts within families. These findings are discussed in relation to pre
      existing literature, and applications are suggested for family intervention
      following ABI.

PMID- 17454692
TI  - An exploratory study of mental representations for rehabilitation based upon the
      Theory of Planned Behaviour.
AB  - This study explores whether mental representations based upon the Theory of
      Planned Behaviour (TPB) can predict engagement in rehabilitation after acquired
      brain injury (ABI). A scale was developed to measure: treatment outcome beliefs,
      perceived barriers, subjective norm, and control cognitions. Other adjustment
      factors that are often seen as important in predicting engagement, e.g., denial
      and anger, were also measured using the Motivation for Traumatic Brain Injury
      Questionnaire (MOT-Q). Clinicians also provided ratings of patient's engagement
      in rehabilitation which was used as the measure of actual behaviour. The scales
      were administered to 40 participants with ABI who were a mean of 14 months post
      injury. The new scale showed good internal reliability, and regression analyses
      demonstrated that "treatment outcome beliefs" were the main aspects of TPB that
      predicted engagement. Control beliefs and adjustment factors added very little to
      the variance in engagement that was already explained by TPB. However, the amount
      of variance that was explained by TPB was small and it is suggested that other
      volitional factors need to be considered in order to predict engagement more
      accurately. This study thus constitutes a first exploration of mental
      representations about rehabilitation after ABI using TPB. It suggests a
      theoretical model that may help clinicians to formulate lack of engagement. It
      also suggests that addressing patients' beliefs about the benefits of undertaking
      rehabilitation may prove fruitful in increasing engagement.

PMID- 17454693
TI  - The Behavioural Assessment of the Dysexecutive Syndrome (BADS) in schizophrenia
      and its relation to functional outcomes.
AB  - The purpose of this study was to establish further the validity of the
      Behavioural Assessment of the Dysexecutive Syndrome (BADS) in a population with
      schizophrenia. Specific objectives were: to examine the construct validity and
      sensitivity of the BADS in differentiating between adult inpatients during an
      acute episode of illness, adult outpatients in the chronic stages of illness, and
      healthy controls; and to examine the predictive validity of the BADS regarding
      functional outcomes within the chronic group. Participants were 30 inpatients
      during an acute episode of their illness; 31 outpatients in the chronic stage;
      and 93 healthy controls. Instruments included the BADS, the Neurobehavioral
      Cognitive Status Examination (Cognistat) and the Routine Task Inventory (RTI).
      Significant differences in BADS scores were found between participants with
      schizophrenia and healthy controls, and between both groups of patients, showing
      the chronic group to have more deficits in executive functions. In addition,
      within the chronic group the BADS was found to be a significant predictor of two
      of the RTI outcome areas, instrumental activities of daily living (IADL) and
      communication, beyond that accounted for by basic cognitive skills. These results
      support the validity of the BADS within the schizophrenic population, and
      highlight the importance of measuring executive functions for rehabilitation.

PMID- 17454694
TI  - A forensic peer group approach to bullying after traumatic brain injury.
AB  - A forensic peer group programme adapted for bullying behaviour and antisocial
      attitudes in three young men with traumatic brain injury (TBI) is presented.
      Three TBI clients who had previously been resistant to an intensive
      neurobehavioural rehabilitation residential programme were enrolled into the
      EQUIP programme. EQUIP focused on teaching pro-social skills as they related to
      aggression, increasing moral development, and altering pro-aggressive attitudes.
      The group ran four days per week over six weeks, with each session lasting 30
      minutes. Post-group assessment indicated that two of the three participants
      altered their beliefs regarding antisocial behaviour. At three-month follow up,
      of the two who demonstrated change one had returned to baseline while the other
      had maintained his progress. Aggression and bullying behaviour reduced in all
      three clients during the EQUIP programme and these improvements were maintained
      at three-month follow up. Self-esteem measures did not alter across the
      assessment period. Antisocial beliefs and their potential for change in clients
      with severe TBI are discussed.

PMID- 17454695
TI  - Efficacy of rehabilitation for functional skills more than 10 years after
      extremely severe brain injury.
AB  - PURPOSE: To determine whether gains in personal independence can be achieved in
      individuals 10 or more years after very severe acquired brain injury. METHOD:
      Four individuals in a continuing (slow stream) rehabilitation centre were
      assessed by an occupational therapist (OT) and programmes were designed to help
      the individual enhance personal independence. Support staff were trained to
      implement these programmes under the guidance of the OT. Methods described by
      Giles, Ridley, Dill, and Frye (1997) were used. Pre- and post-training measures
      were taken as well as follow up measures to assess the durability of such
      changes. RESULTS: The results demonstrate that it is possible to achieve
      clinically significant improvements in personal independence many years after
      very severe acquired brain injury. CONCLUSIONS: The findings of this study
      suggest that personally and clinically significant goals can be achieved 10 or
      more years after brain injury and there should be continuing effort to improve
      the circumstances of individuals with acquired brain injury. Such gains can be
      achieved through consistent application of such programmes by support workers
      working under the supervision of an occupational therapist.

PMID- 17454696
TI  - Semantic-phonologic treatment for noun and verb retrieval impairments in aphasia.
AB  - Nouns and verbs differ in their neural and psycholinguistic attributes. It is not
      known whether these differences lead to distinct patterns of response to
      treatment for individuals with word retrieval impairments associated with
      aphasia. Eight participants with naming disorders induced by left hemisphere
      strokes were treated with a semantic-phonologic treatment protocol for nouns and
      verbs using a single participant multiple baseline design. We measured treatment
      gains in a picture naming measure and other secondary language and communication
      measures. Treatment led to improved picture naming for trained nouns and verbs in
      five of eight patients, with no difference evident between nouns and verbs.
      Improvements for untrained words were minimal. Improvement in verb retrieval was
      associated with increases on a functional measure of communicative effectiveness.
      Improvement for nouns and verbs was associated with severity of word retrieval
      impairment at onset. Although distinct in neural and psycholinguistic attributes,
      nouns and verbs were affected by treatment in a similar pattern in this group of
      individuals. Training-specific effects suggest the need for careful selection of
      training words to have potential for functional benefit in daily communication.

PMID- 17454697
TI  - What's new in Nicotine & Tobacco Research?

PMID- 17454698
TI  - Depression during tobacco abstinence.
AB  - Many clinicians and scientists believe smoking cessation increases the risk of
      major depressive disorder (MDD), especially among those with a past history of
      the disorder. This literature review located seven empirical tests of this
      belief. All seven had significant methodological limitations. The incidence of
      MDD over 7-64 weeks postcessation was 0%-14% among all smokers who tried to stop,
      3%-24% among smokers with a past history of MDD who tried to stop, and 1%-31%
      among smokers who became abstinent. Smokers with a past history of MDD were more
      likely to have postcessation MDD. Although some within-study comparisons suggest
      abstinence increased the incidence of MDD, a definitive conclusion cannot be
      made. Whether treatment with antidepressants prevented postcessation MDD also was
      unclear. This review makes methodological recommendations for more definitive
      studies.

PMID- 17454699
TI  - Sociocultural correlates of menthol cigarette smoking among adult African
      Americans in Los Angeles.
AB  - Nearly 70% of adult African American smokers smoke menthol cigarettes. More
      information is needed about the psychological, social, and cultural factors that
      influence their overwhelming preference for menthol cigarettes. This study
      examined variables associated with menthol vs. nonmenthol cigarette use among 432
      adult African American smokers in Los Angeles, California. Menthol smoking was
      most prevalent among women, 18-30-year-olds, and employed respondents.
      Controlling for age and employment, we found that the significant correlates of
      menthol use among women were parents' menthol smoking, the belief that most
      African American smokers smoke menthols, and disagreement with the belief that
      smoking menthol cigarettes is a "Black thing." Among men, the only significant
      correlate of menthol smoking was the belief that most African American smokers
      smoke menthols. Results indicate that menthol smoking among adult African
      Americans is at least partly a consequence of a complex set of social and
      cultural norms. Further research is needed to understand the reasons why so many
      African Americans select menthols, as well as the health consequences of these
      choices.

PMID- 17454700
TI  - Modeling the relationship of cotinine and self-reported measures of maternal
      smoking during pregnancy: a deterministic approach.
AB  - Studies of effects of prenatal exposure to cigarettes frequently acquire both
      self-report and biological assays of maternal smoking. However, little attention
      has been paid to methods for combining information from both sources to enhance
      the precision of exposure measurement. This paper analyzes the relationship
      between the two commonly used measures of smoking exposure during pregnancy:
      Maternal self-report and urinary cotinine. We present a deterministic method for
      combining the two measures and examine its robustness under different
      assumptions. We apply the method to a dataset from the Family Health and
      Development Project. In addition, we propose an approach for calibrating the self
      report measures for individual women based on both sources of information.
      Enhancing the quality of exposure measurement may substantially advance studies
      of the teratological effects of exposure on offspring.

PMID- 17454701
TI  - Belief about drug assignment and abstinence in treatment of cigarette smoking
      using nortriptyline.
AB  - This study assessed the relationship between beliefs about drug assignment and
      abstinence status in two treatment studies using nortriptyline hydrochloride as
      an adjunct to smoking cessation. Smokers (N = 345) drawn from two clinical trials
      were asked at the final follow-up (FFU) at 52 or 64 weeks whether they believed
      they had received active or placebo drug. Responses were obtained from 262
      participants, or 76% of the sample. Biochemically verified abstinence was
      collected at end of treatment (EOT) and FFU. In both studies, participants were
      correct in guessing drug assignment. At FFU, belief about drug assignment was not
      related to abstinence for either active or placebo participants. Participants who
      received active drug and who were smoking at EOT were more likely to believe they
      had received placebo than active drug participants who were abstinent at EOT. We
      found no significant relationship between belief about drug and abstinence status
      for placebo participants at EOT. Baseline variables did not significantly predict
      correctness of drug identification. Participants who experienced drug side
      effects not easily attributable to nicotine withdrawal were more likely to
      identify their drug assignment as nortriptyline. We conclude that experience
      during the active treatment period, including side-effects and treatment success,
      may be related to belief about drug assignment, that the field would be well
      served by at least two assessments of blindness in clinical trials, and that
      discrepancy between these findings and those regarding nicotine replacement
      therapy may be related to differences in dependent variables.

PMID- 17454702
TI  - The impact and acceptability of Canadian-style cigarette warning labels among
      U.S. smokers and nonsmokers.
AB  - Cigarette smoking is a major source of mortality and medical costs in the United
      States. More graphic and salient warning labels on cigarette packs as used in
      Canada may help to reduce smoking initiation and increase quit attempts. However,
      the labels also may lead to defensive reactions among smokers. In an experimental
      setting, smokers and nonsmokers were exposed to Canadian or U.S. warning labels.
      Compared with current U.S. labels, Canadian labels produced more negative
      affective reactions to smoking cues and to the smoker image among both smokers
      and nonsmokers without signs of defensive reactions from smokers. A majority of
      both smokers and nonsmokers endorsed the use of Canadian labels in the United
      States. Canadian-style warnings should be adopted in the United States as part of
      the country's overall tobacco control strategy.

PMID- 17454703
TI  - Anxiety sensitivity and early relapse to smoking: a test among Mexican daily, low
      level smokers.
AB  - The aim of the present investigation was to extend previous work on anxiety
      sensitivity (AS) and early smoking relapse among a sample of 130 (74 females)
      young adult (M (age) = 22.5 years, SD = 2.1) daily low-level smokers (9.3
      cigarettes/day, SD = 11.5) from Mexico City, Mexico. Results indicated that of
      the global-level and lower-order factors (i.e., physical, mental incapacitation,
      and social concerns) on the Anxiety Sensitivity Index, only the physical concerns
      factor was significantly related to early lifetime smoking relapse. This effect
      was observed above and beyond the effects of negative affectivity, cigarettes
      smoked per day, and alcohol consumption, as well as beyond the other AS mental
      and social concerns factors. Findings provide novel evidence that AS is an
      important explanatory construct in early smoking relapse.

PMID- 17454704
TI  - Sex-based and hormonal contraception effects on the metabolism of nicotine among
      adolescent tobacco-dependent smokers.
AB  - Variations in nicotine metabolism influence smoking patterns. Differences between
      sexes or related to sex hormones may affect nicotine metabolism. Because smoking
      initiation starts during adolescence, observations gathered from adolescent
      smokers might broaden our understanding of such sex-based differences. We tested
      the hypothesis that nicotine metabolism--as indexed primarily by the ratio of
      trans-3'-hydroxycotinine (3HC) to cotinine--is more rapid among adolescent girl
      smokers compared with boys and that regular use of hormonal contraceptives
      influences nicotine and cotinine metabolism. We also hypothesized that more rapid
      nicotine metabolism is associated with higher nicotine dependence as indexed by
      smoking frequency and morning urgency. Plasma samples of nicotine, cotinine, and
      3HC concentrations were obtained from 120 adolescents (36 boys). Plasma nicotine
      and cotinine concentrations were similar in boys and girls. Median plasma 3HC
      concentrations were 44.45 ng/ml for girls versus 35.74 ng/ml for boys (p = .025),
      and median plasma 3HC-cotinine ratios were significantly higher in girls than in
      boys (0.317 vs. 0.253, p = .025). After stratifying girls into two groups based
      on use versus nonuse of hormonal contraception, plasma 3HC-cotinine ratios in
      girls using hormonal contraception (0.47) were substantially higher (p<.0001)
      than in boys (0.25) and were significantly higher than in girls not using
      hormonal contraception (0.28). Controlling for cigarettes smoked per day,
      ethnicity, and age did not modify these results. Although plasma nicotine,
      cotinine, or 3HC concentrations were significantly lower in less dependent
      adolescent smokers, nicotine and cotinine metabolite ratios were similar. This
      study showed that hormonal contraception in adolescent girls may accelerate
      cotinine metabolism, an effect likely related to induction of cytochrome P450 2A6
      and independent of ethnicity and cigarette consumption. Prospective controlled
      studies are needed to further evaluate the role of hormonal contraception in
      patterns of adolescent smoking and nicotine metabolism.

PMID- 17454706
TI  - The effects of foods, beverages, and other factors on cigarette palatability.
AB  - While smokers commonly report that various foods and beverages worsen or enhance
      the taste of cigarettes, the prevalence and diversity of these phenomena have not
      been studied. We administered an open-ended questionnaire to 209 smokers asking
      for reports of foods or beverages that worsen or enhance the taste of cigarettes.
      Commonly reported categories that worsen the taste of cigarettes were
      fruits/vegetables, noncaffeinated beverages, and dairy products. Commonly
      reported categories that enhance the taste of cigarettes were caffeinated and
      alcoholic beverages, and meat products. Regression analyses indicated that
      increased sensitivity to both taste worsening and enhancing were associated with
      smoking nonmenthol cigarettes. These findings suggest smoking menthol cigarettes
      reduces both negative and positive effects of food and beverage consumption on
      smoking satisfaction - thus "evening out" the smoking experience. Clinical
      implications and directions for future research are discussed.

PMID- 17454705
TI  - Sensitivity and specificity of a reagent-impregnated test strip in identifying
      smokeless tobacco users.
AB  - This study was designed to determine the sensitivity and specificity of a reagent
      impregnated test strip in identifying habitual snuff users and tobacco chewers.
      Urine specimens were obtained from smokeless tobacco users and controls and blind
      tested on-site using a reagent-impregnated test strip. Samples also were sent to
      our university hospital lab for cotinine and nicotine analysis by gas
      chromatography (GC). The test strip results were compared with GC results and
      self-reported use of snuff and chewing tobacco. A total of 61 subjects enrolled
      in the study: 26 snuff users, 25 tobacco chewers, and 10 nonconsumers of
      nicotine. Using GC assessment of nicotine and cotinine (>or=200 ng/ml) as the
      standard, we found the sensitivity of the test strip to be 96% (25/26) for snuff
      users and 96% (24/25) for tobacco chewers. When compared with self-report, the
      sensitivity of the test strip was 92.3% (24/26) for snuff users and 84% (21/25)
      for tobacco chewers. The specificity for nonusers of nicotine was 100% (10/10)
      for both the self-report and GC conditions. These results suggest that a reagent
      impregnated test strip is a rapid, valid, and user-friendly means of
      differentiating smokeless tobacco users from nonconsumers of tobacco. The
      intensity of the pink color on the test strip is proportional to the amount of
      nicotine or its metabolites present in urine and therefore offers a
      semiquantitative measure of nicotine consumption.

PMID- 17454707
TI  - An association of CYP2A6 genotype and smoking topography.
AB  - Nicotine is metabolized into biologically inactive cotinine primarily by the
      cytochrome P450 enzyme CYP2A6. CYP2A6 genetic variations have been phenotypically
      grouped as slow, intermediate, and normal metabolizers. Slow metabolizers smoke
      fewer cigarettes daily and weekly, and have lower carbon monoxide (CO) and plasma
      nicotine levels, suggesting a reduced smoking rate compared with normal
      metabolizers. CYP2A6 also is involved in the metabolic activation of tobacco
      specific procarcinogenic nitrosamines, such as 4-(methyl-nitrosamino)-1-(3
      pyridyl)-1-butanone (NNK) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanol
      (NNAL). NNK is one of the most abundant and potent procarcinogens in cigarette
      smoke. The present study investigated the association of CYP2A6 genotype with
      smoking topography, a quantifiable measure of smoking behavior, in a sample of
      treatment-seeking smokers prior to treatment. Smoking topography measures
      indicative of quantity of smoke exposure--number of puffs, mean puff volume, and
      total puff volume--were the outcome variables. Covariates associated with smoking
      topography were included in the analyses. Results indicated that CYP2A6 genotype
      group had a significant effect on mean puff volume and total puff volume, but not
      number of puffs, such that slow metabolizers exhibited reduced puffing compared
      with others. Smokers having CYP2A6 variants resulting in low activity metabolize
      nicotine more slowly, and convert procarcinogen nitrosamines to carcinogens more
      slowly, than do normal metabolizers. The results from this study also suggest a
      behavioral mechanism that may account for reduced cancer risk in slow
      metabolizers.

PMID- 17454709
TI  - Literature review and summary of perceptions, attitudes, beliefs, and marketing
      of potentially reduced exposure products: communication implications.
AB  - Potentially reduced exposure products (PREPs) have continued to enter the market
      during the 1990s and first part of the 21st century. Attempts by the tobacco
      industry to develop and market products with implied reductions in adverse health
      effects (i.e., harm reduction) are not new. Over the last half of the 20th
      century, the tobacco industry developed and marketed several products that
      purported to reduce the health risks associated with smoking cigarettes. Among
      these were filtered cigarettes in the 1950s and light and ultra-light cigarettes
      in the 1970s and 1980s. This review summarizes published and unpublished research
      that is directly relevant to the marketing, advertising, and communication about
      PREPs. The marketing strategies for these new products do not appear to differ
      from those used by the tobacco industry for light and ultra-light cigarettes.
      Although smokers report not using the new products in large numbers because of
      dissatisfaction with taste, they are interested in using products with reduced
      risk. Despite the absence of explicit health claims by the industry for PREPs,
      many smokers believe that these products are safer based on the advertising
      claims of reduced exposure and a belief that claims are approved by the
      government. No data are available to indicate that PREPs are useful for
      prevention or cessation of smoking, nor does specific research exist to suggest
      what health communication messages will provide smokers with accurate information
      about these products.

PMID- 17454710
TI  - Weight concerns and cognitive style: which carries more "weight" in the
      prediction of smoking among college women?
AB  - Although weight concerns and smoking are related, anorexic and bulimic women,
      both of whom have elevated weight concerns, have significant differences in
      smoking status. Fewer anorexic women smoke, compared with bulimic women,
      suggesting that weight concerns do not fully explain smoking status. This study
      investigated the contribution of one factor, cognitive style, to differences in
      smoking status among college women with different levels of weight concerns:
      Anorexic tendencies (n = 47), bulimic tendencies (n = 62), weight concerns (n =
      56), and no weight concerns (n = 76). Nearly 47% of women with bulimic
      tendencies, 37.5% of women with weight concerns, and 27.7% of women with anorexic
      tendencies were current smokers. A total of 22% of women without weight concerns
      were current smokers. A logistic regression model revealed that race, age, the
      Personal Standards subscale of the Frost Multidimensional Perfectionism Scale,
      the Self-Control and Self-Esteem subscale of the Brief Mizes Anorectic Cognitions
      Questionnaire, and membership in the bulimic tendencies category were significant
      independent predictors of smoking status. Both weight concerns and cognitive
      style variables, including perfectionism and self-control, carried "weight" in
      the prediction of smoking among college women. In light of these findings,
      treatment research should explore both the behavioral and cognitive factors
      associated with weight-concerned college smokers.

PMID- 17454711
TI  - The role of ethnicity and neighborhood poverty on the relationship between
      parenting and adolescent cigarette use.
AB  - Although etiological models of substance use may be different across ethnic
      groups, how ethnicity might moderate the influence of causal factors is not
      frequently tested. The influence of parenting on adolescent cigarette smoking may
      vary across Black and White adolescents. Recent research suggests that parenting
      may be more strongly predictive of substance use among Blacks. Black parents not
      only may feel more efficacious in their parenting, compared with their White
      counterparts, but also may be more likely to set strict rules against smoking. As
      a result, Black parents may be more effective in preventing their children from
      engaging in smoking behavior. Also, research suggests that these ethnic
      differences may vary across community contexts. The present study examined cross
      sectionally and longitudinally how ethnicity moderates the relationship between
      parenting and adolescent cigarette use, and how this moderating effect varies
      across levels of community risk. A three-way ethnicity x parenting x community
      risk interaction was tested in a sample of adolescents selected from the National
      Longitudinal Study of Adolescent Health (Add Health). In general, positive
      parenting behaviors (e.g., high parental control, high-quality relationship) were
      related to lower levels of smoking for both Black and White youth; however, when
      differences were found, this relationship was stronger for Whites. Also, the
      influence of neighborhood poverty was limited to smoking for White adolescents
      such that higher levels of neighborhood poverty were associated with increased
      smoking for White but not Black adolescents. These differences may be related to
      several factors, including how children are socialized in Black and White
      families, ethnic differences in reasons for using substances or abstaining, and
      differences in susceptibility to social influences.

PMID- 17454712
TI  - Nicotine dependence symptoms among adolescents with psychiatric disorders: using
      a Rasch model to evaluate symptom expression across time.
AB  - Little is known about the longitudinal course of symptoms of nicotine dependence
      among adolescents following interventions designed to affect smoking behavior,
      particularly among high-risk samples. We used an item-response modeling strategy
      to examine how well nicotine dependence symptoms cohere to a latent construct,
      the stability of the construct over time, and the sensitivity of the nicotine
      dependence symptoms to changes in smoking patterns among adolescents with
      comorbid psychopathology. Assessments occurred prior to cessation treatment
      delivered within a randomized clinical trial and again at 6 and 12 months after
      treatment. We used a Rasch item-response modeling approach to examine nicotine
      dependence as measured by a structured Adolescent Nicotine Dependence Interview
      (ANDI) and by the Modified Fagerstrom Tolerance Questionnaire (mFTQ). These
      analyses provided support for a unidimensional latent measurement model that can
      be used to organize symptoms of nicotine dependence obtained from ANDI and mFTQ
      measures. The derived measure showed good construct validity with significant
      relationships to smoking levels and salivary cotinine levels. The typical symptom
      patterns and the relative severity of nicotine dependence symptoms remained
      stable over multiple assessments. Changes in smoking levels were related
      longitudinally to changes in nicotine dependence, and changes in nicotine
      dependence were related to changes in motivation to quit and readiness to change
      smoking behavior. Several behavioral symptoms were sensitive to change in smoking
      rate over time, whereas core symptoms of physiological dependence did not
      evidence significant changes. Results suggest that DSM-IV and mFTQ measures of
      nicotine dependence provide complementary information when assessing nicotine
      dependence levels among adolescents with psychiatric disorders.

PMID- 17454713
TI  - Smokers' attitudes and behaviors related to consumer demand for cessation
      counseling in the medical care setting.
AB  - This study describes a new segmentation strategy exploring smokers' interest
      levels in counseling in the medical care setting in order to understand how
      public health communications can be designed to increase consumer demand for
      cessation services within this population. A subsample of 431 smokers from a
      large, nationally representative mail survey was analyzed and categorized into
      three cessation-demand groups: Low demand (LD), medium demand (MD), and high
      demand (HD). HD smokers were most likely to be heavy smokers, to make quitting a
      high priority, and to have self-efficacy in quitting. MD and LD smokers were less
      likely than HD smokers to have been told to quit smoking by a health care
      provider in the past or to believe that counseling is effective. The first step
      in the regression analysis revealed that age, cigarettes smoked per month,
      whether smokers were currently trying to quit, and whether they were ever told to
      quit smoking by their health care provider accounted for 21% of the variance in
      smokers' interest in smoking cessation counseling, F(4, 234) = 16.49, p<.001.
      When additional variables on attitudes toward smoking and quitting and perceived
      effectiveness of receiving counseling in the medical care setting were added to
      the model, an additional 11% of the variance in smokers' interest in cessation
      counseling was explained, F(12, 234) = 10.07, p<.001. Results suggest that by
      categorizing smokers by interest level in cessation counseling, we emerge with
      three distinct portraits of smokers who might be activated in different ways to
      increase consumer demand for cessation counseling.

PMID- 17454714
TI  - Proactive recruitment of health plan smokers into telephone counseling.
AB  - We tested whether a 3-month beneficial effect of telephone counseling as an
      adjunct to the use of medications for smoking cessation was maintained through 12
      months. Health plan members filling a prescription for cessation medications were
      randomized either to a no-contact control group or to proactive recruitment into
      telephone counseling. An increased point-prevalence quit rate at 3 months (33.1%
      vs. 27.4%, p<.05) among smokers randomized to proactive recruitment for telephone
      counseling was not maintained. Although at 12 months smokers in the proactive
      recruitment arm were more likely to report a 24-hr quit attempt, compared with
      control group smokers (86.7% vs. 80.8%, p = .027), we found no differences
      between the groups in repeated (3-month and 12-month) 7-day point-prevalence quit
      rates. In an analysis of predictors of quitting, age, marital status, making a
      lifestyle change, and the presence of household smokers were associated with
      repeated 3-month and 12-month point-prevalence abstinence. Offering telephone
      counseling to insured smokers who have filled prescriptions for cessation
      medications did not increase long-term quit rates. Although other variations of
      this approach might be tested, we suspect that it might be more useful to test
      innovative ways to influence the factors we identified as being most strongly
      predictive of lack of successful quitting.

PMID- 17454715
TI  - Comparison of cigarette and water pipe smoking among female university students
      in Egypt.
AB  - This study investigated behavioral and sociodemographic factors associated with
      tobacco use among female university students patronizing water pipe cafes in
      Cairo, Egypt. We interviewed two groups of female university student smokers (100
      and 96 students from a public and a private university, respectively). The
      interviews took place in nine water pipe cafes near the two universities. A
      logistic regression model was developed to analyze the relationship between
      tobacco-related knowledge and beliefs and the choice between smoking water pipe
      or cigarettes. Among these smokers, 27% smoked cigarettes only, 37.8% smoked
      water pipe only, and 35.2% smoked both types of tobacco. Most of the water pipe
      smokers (74.1%) preferred this method because they believe it to be less harmful
      than smoking cigarettes. More than half of the subjects were encouraged to start
      smoking by other females (56.6%). Curiosity was a significant factor for
      initiation (OR = 2.8, 95% CI = 1.3-6.2, p<.01). We found no significant
      differences between water pipe and cigarette smokers regarding current age, age
      at initiation, quit attempts, knowledge about the hazards of smoking, wanting to
      be fashionable, or smoking with friends. About one in four (23.7%) attempted to
      quit, with health cited as a major reason. An urgent need exists for correction
      of the misperception among this study population that water pipe smoking is safe
      and less harmful than cigarette smoking.

PMID- 17454717
TI  - Tobacco cessation drug therapy among Canada's Aboriginal people.
AB  - The smoking rate among Aboriginal people is more than double the rate of the rest
      of the Canadian population, and smoking is a major source of morbidity and
      mortality within this population. Tobacco cessation drug therapy use among
      Aboriginal smokers is very low. We administered a cross-sectional questionnaire
      to Aboriginal and non-Aboriginal smokers or recent ex-smokers in 12 First Nations
      communities in two Canadian provinces from September to December 2004.
      Participants were asked about smoking cessation advice and perceptions of three
      drug therapy agents. The overall response rate was 82% (407 Aboriginal and 102
      non-Aboriginal smokers or ex-smokers). A substantial proportion reported tobacco
      cessation or reduction in the previous year (Aboriginal 46% vs. non-Aboriginal
      32%). Aboriginal participants were less likely to seek physician services
      (prevalence OR [pOR] = 0.45, 95% CI = 0.27-0.74, p = .001) and less willing to
      use nicotine patch (pOR = 0.6, 95% CI = 0.38-0.96, p = .03) or bupropion (pOR =
      0.50, 95% CI = 0.29-0.84, p = .008). Among First Nations participants, who
      receive a drug therapy subsidy, lack of awareness of the subsidy were associated
      with less willingness to use drug therapy; further, the requirement for a
      physician prescription was perceived as a barrier. Among all participants,
      utilization of physician services (pOR = 2.2, 95% CI = 1.50-3.20, p<.001) and
      receiving drug therapy advice from a physician (pOR = 7.7, 95% CI = 4.17-14.3,
      p<.001) was associated with willingness to use drug therapy. In conclusion, many
      Aboriginal smokers are interested in and attempt cessation, but underutilization
      of physician services and low willingness to use drug therapy may explain their
      lower use of drug therapy. Physicians need to provide advice on drug therapy, and
      policy makers should eliminate the need for a physician prescription. Future
      studies can explore cultural attitudes toward cessation drug therapy and
      physician services.

PMID- 17454716
TI  - Factor structure and validity of the Medication Adherence Questionnaire (MAQ)
      with cigarette smokers trying to quit.
AB  - The Medication Adherence Questionnaire (MAQ) is a scale used to evaluate
      adherence to medications. The present study assessed the factor structure and
      validity of the MAQ with cigarette smokers. A principal components analysis was
      conducted on MAQ scores from a sample of smokers presenting for treatment in a
      clinical trial of naltrexone and nicotine patch for smoking cessation (N = 385).
      Indices of convergent and predictive validity were tested using electronic
      medication caps for naltrexone, nicotine patch counts, plasma drug levels of
      naltrexone, and treatment outcomes. The principal components analysis revealed
      two factors. Factor 1, labeled "unintentional nonadherence," measured the extent
      to which individuals were nonadherent because they were careless or forgot to
      take their medications. Factor 2, labeled "purposeful nonadherence," assessed
      nonadherence related to purposefully stopping medication use after feeling better
      or worse. Only the second factor was shown to have good convergent and predictive
      validity. Specifically, this factor was related to pill-taking behavior measured
      with electronic medication caps and drug plasma levels and nicotine patch use
      based on nicotine patch count data, and it was associated with smoking cessation
      outcome. Thus the purposeful nonadherence factor of the MAQ may be used as a
      brief screening tool for medication adherence with cigarette smokers seeking
      treatment. Information obtained with this questionnaire could be used to counsel
      patients regarding the importance of medication adherence.

PMID- 17454719
TI  - Relighting cigarettes: how common is it?
AB  - In a representative sample of 434 daily smokers, half reported that they relight
      cigarettes at least some of the time. Relighting cigarettes was positively
      associated with severity of smoking addiction, as well as with being female, with
      markers of lower socioeconomic status (income, employment status), and with
      having less education. Smokers contemplating change were less likely to relight
      cigarettes. Given that previous research has indicated that relighting cigarettes
      leads to increased harm, the public health implications of this smoking practice
      are discussed.

PMID- 17454718
TI  - Carry-over effects of smoking cue exposure on working memory performance.
AB  - The present study investigated the effects of drug cue exposure on working memory
      performance in cigarette smokers. Adult smokers (N = 23) deprived for 12 hr
      performed a working memory task during which they were exposed to three types of
      task-irrelevant stimuli: Pictures containing smoking related-content, pictures
      devoid of smoking content, and a fixation cross. Consistent with prior research,
      we found that drug cue exposure affected the processing of subsequent items
      (i.e., carry-over effects). Specifically, we found that working memory
      performance was worse on trials containing neutral pictures preceded by trials
      containing smoking cues compared with performance on trials containing neutral
      pictures preceded by trials not containing smoking-related stimuli. Previously
      observed effects of smoking cue exposure on cognitive processing were replicated
      but only after removing trials subject to carry-over effects. These results
      replicate and extend previous research demonstrating similar effects and
      highlight the significant methodological and conceptual implications of carry
      over effects.

PMID- 17454720
TI  - Lung cancer risk measured by the Fagerstrom Test for Nicotine Dependence?

PMID- 17454722
TI  - Adolescent pathological gambling in Kaunas, Lithuania.
AB  - This paper presents the results of the first survey of pathological gambling
      among adolescents in Kaunas, Lithuania. The results indicated that a large
      majority of adolescent (82.6%) have engaged in a variety of gambling activities.
      Although most respondents were classified as "occasional gamblers", there were
      significantly more females than males who were occasional gamblers and non
      gamblers, and significantly more males than females who were regular gamblers.
      More adolescents surveyed had gambled on Tele-Lotto than on any other gambling
      activity. Based on Diagnostic statistical manual-IV-Multiple Response-Adapted for
      Juveniles, 4.2% of participants were categorized as pathological gamblers, with a
      further 9.1% classified as at-risk gamblers, 69.4% as social gamblers, and 17.3%
      as non-gamblers. Based on South Oaks Gambling Screen-Revised for Adolescents,
      5.2% (n = 43) of participants were categorized as pathological gamblers, with a
      further 10.5% (n = 88) classified as at-risk gamblers, 67% (n = 559) as social
      gamblers, and 17.3% (n = 145) as non-gamblers. The commonest reason given by
      adolescents for gambling were "enjoyment", "a chance to try luck" and "to win
      money"; however, the top reasons reported for pathological gambling were "to
      relax", "to distract myself from problems" and "to improve mood". Male gender,
      cognitive distortions regarding gambling, having parents who gamble and gamble
      too excess, using alcohol regularly, and smoking regularly were characteristics
      significantly associated with pathological gambling in adolescence.

PMID- 17454723
TI  - Risky use and misuse of alcohol, drugs and cigarettes detected by screening
      questionnaires in a clinical psychosis unit.
AB  - The use of screening instruments has been proposed to facilitate identification
      of risky substance use and misuse. This study aims to investigate the use of a
      screening procedure to identify hazardous or harmful use of alcohol, drug-related
      problems and riskful use of cigarettes in a clinical psychosis setting. The use
      of alcohol, drugs and cigarettes was examined by three self-reporting
      instruments: Alcohol Use Disorders Identification Test (AUDIT), Drug Use
      Disorders Identification Test (DUDIT) and Fagerstrom Test for Nicotine Dependence
      (FTND). Two hundred and forty-one out of 374 patients (64%) took part in the
      investigation. Eighteen per cent had a hazardous or harmful alcohol use, 9% drug
      related problems and 49% were smokers. Multivariate analyses showed that women,
      as well as smokers had an increasing risk of having drug-related problems. The
      use of screening questionnaires increases the awareness that risky use of
      alcohol, drugs and cigarettes is common among persons with psychosis. Many
      persons with psychosis used alcohol, drugs and cigarettes in a risky way. It is
      important to identify these problems to make proper interventions due to the
      negative medical and social consequences of this use. Such identification may be
      facilitated by use of screening instruments.

PMID- 17454724
TI  - A Danish cost-effectiveness model of escitalopram in comparison with citalopram
      and venlafaxine as first-line treatments for major depressive disorder in primary
      care.
AB  - The objective of this study was to model the cost-effectiveness of escitalopram
      in comparison with generic citalopram and venlafaxine in primary care treatment
      of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg
      Depression Rating Scale, MADRS) in Denmark. A three-path decision analytic model
      with a 6-month horizon was used. All patients started at the primary care path
      and were referred to outpatient or inpatient secondary care in the case of
      insufficient response to treatment. Model inputs included drug-specific
      probabilities derived from systematic literature review, ad-hoc survey and expert
      opinion. Main outcome measures were remission defined as MADRS < or = 12 and
      treatment costs. Analyses were conducted from healthcare system and societal
      perspectives. The human capital approach was used to estimate societal cost of
      lost productivity. Costs were reported in 2004 DDK. The expected overall 6-month
      remission rate was higher for escitalopram (64.1%) than citalopram (58.9%). From
      both perspectives, the total expected cost per successfully treated patient was
      lower for escitalopram (DKK 22,323 healthcare, DKK 72,399 societal) than for
      citalopram (DKK 25,778 healthcare, DKK 87,786 societal). Remission rates and
      costs were similar for escitalopram and venlafaxine. Robustness of the findings
      was verified in multivariate sensitivity analyses. For patients in primary care,
      escitalopram appears to be a cost-effective alternative to (generic) citalopram,
      with greater clinical benefit and cost-savings, and similar in cost-effectiveness
      to venlafaxine.

PMID- 17454725
TI  - The influence of educational information on depressed outpatients treated with
      escitalopram: a semi-naturalistic study.
AB  - This open-label multicentre semi-naturalistic study in Finland assessed the
      impact of educational information on efficacy of 16-week treatment with
      escitalopram (5-20 mg/day) in a patient population suffering from depression.
      Patients were randomized single blind to receive educational information (n=79)
      or no information (n=78) in addition to open-label escitalopram treatment.
      Patients were assessed using the Montgomery-Asberg Depression Rating Scale
      (MADRS), Clinical Global Impression - Severity and - Improvement (CGI-S and CGI
      I), Patient Global Evaluation (PGE), and Hopkins Symptom Checklist (SCL-90)
      scales. Tolerability was assessed by the incidence of adverse events (AEs). A
      total of 132 (84%) out of 157 patients completed the study, with similar
      completer rates in both groups. There was no statistically significant effect of
      educational information on the efficacy of escitalopram treatment, as measured by
      MADRS, CGI and PGE. Mean MADRS total score was 25.3 at baseline, corresponding to
      moderate to severe depression, and decreased to 7.9 at the end of the treatment
      for both groups. The response rate (> or = 50% reduction in MADRS total score
      from baseline) was 80% at the end of treatment for both groups. The clinical
      relevance of the improvement was seen in CGI-I and PGE scores and there was a
      strong correlation between the two scales, indicating agreement by both patients
      and investigators. AEs were mostly mild and transient and 11 patients (7.0%)
      dropped out of the study due to AEs, with similar incidence in both groups.
      Escitalopram was effective and well tolerated in the treatment of depression over
      a 16-week period in a semi-naturalistic setting, and an additional effect of
      educational information could not be shown, possibly due to the high response to
      treatment.

PMID- 17454726
TI  - Women with a history of childhood sexual abuse. Long-term social and psychiatric
      aspects.
AB  - The socio-demographics and psychiatric diagnoses in a clinical sample of women
      with a history of mainly intrafamilial childhood sexual abuse (CSA) are
      described. The women were referred to five psychiatric centres for incest group
      psychotherapy. Data were gathered using interviews and self-administered
      questionnaires. Over a period of 2.5 years, 385 women with mean age of 33 years
      were referred with a history of CSA. Three hundred and forty of those had
      experienced intrafamilial CSA. The average age at first abuse was 6.8 years, and
      it lasted for a mean of 6 years. The women had been abused by a mean of 1.5
      perpetrators. A quarter of the women had been subjected to violence in connection
      with the sexual abuse. The likelihood of violence having occurred rose
      significantly if there was more than one perpetrator and/or if penetration had
      been part of the sexual abuse. Violence was less common if the perpetrator was a
      brother. The women suffered from a broad spectrum of psychiatric symptoms and
      illnesses. More than half of the women had previously received psychiatric
      treatment. Compared to a random sample of the general female population, these
      women were less advantaged with regards to education, financial circumstances and
      cohabitation. The results emphasize the importance of offering comprehensive
      social and psychiatric intervention to help reducing the problems following CSA
      in women.

PMID- 17454727
TI  - Staff injuries after patient-staff incidences in psychiatric acute wards.
AB  - The aim of the study was to describe the pattern of injuries to various body
      parts in patient-staff incidents; 507 patient-staff incidents in a psychiatric
      acute ward during the period 1990-1997 were included. Staff members registered
      193 injuries in the head, 112 in the trunk, 265 in the upper extremities and 69
      in the lower extremities. No differences between the two sexes or between
      different levels of education among the nurses were found in the pattern of
      injuries. Doctors were more often injured in the head and less often injured in
      the upper extremity than the nurses. The head was more often injured when there
      was no understandable provocation before the incident and seldom injured when the
      patients were denied something. Injuries to the trunk were more frequently
      followed by use of parenteral medication. Parenteral medication and holding the
      patient with force were more frequently used in incidents where more than one
      body part was injured. The knowledge of injures after patient-staff incidences
      may contribute to the education and protective training of the staff of
      psychiatric acute wards.

PMID- 17454728
TI  - Reliability and validity of a Swedish version of the Dissociative Experiences
      Scale (DES-II).
AB  - The aim was to investigate the psychometric properties, i.e. reliability
      (internal consistency) and validity (factor structure and relationships with
      other scales) of the Dissociative Experiences Scale (DES) in a random sample from
      the Swedish population. Six hundred subjects between 18 and 59 years of age were
      randomly sampled from the population of a catchment area in a suburb of Stockholm
      and 181 patients with a range of post-traumatic disorders were included. A second
      order analysis revealed two components, which reflected normal and pathological
      dissociation, and could readily be summed into one scale. The internal
      consistency was high (Cronbach's alpha=0.87). High scorers in the DES had more
      fearful attachment, more interpersonal problems, more severe symptoms and lower
      sense of coherence. A subgroup of patients with significant dissociation was
      identified. The psychometric properties are sufficient for use of the DES as a
      screening instrument for dissociative symptoms.

PMID- 17454729
TI  - Evaluation of the Incredible Years Series - an open study of its effects when
      first introduced in Sweden.
AB  - Behaviour management problems (BMP) are common among children (4-12%) and the
      prevalence seems to be rising. Persistent antisocial behaviour often leads to
      poor long-term psychosocial adjustment. Structured parent-training programmes
      have proven to be the most effective way of treating BMP in young children. The
      Incredible Years Series (IYS), which is a manual-based programme, was introduced
      in Sweden in 2001. The aim of the present study was to evaluate the effectiveness
      of IYS in diverse clinical settings in Sweden. Parents of 113 children (3-9
      years), recruited through the IYS-trained group leaders' ordinary services,
      participated in the study. The parents answered various questionnaires regarding
      their children's symptoms and their own psychological well-being before and after
      participating in the parent-training groups. The results are very encouraging;
      significant reduction of BMP in the children was found on all relevant measures.
      A significant increase in the self-rated well-being of the mothers was also
      found. The IYS seems to work in Sweden, even when used by group leaders who are
      in training. The importance of using a well-documented manualized method when
      implementing new models is accentuated.

PMID- 17454730
TI  - On the relationship of atypical and low-dose conventional antipsychotics with
      akathisia in a clinical patient population.
AB  - Metabolic side-effects of atypical antipsychotics have led to concern about their
      relative safety compared with low doses of conventional neuroleptics. Akathisia
      is an often misdiagnosed side-effect, which leads to non-compliance and sometimes
      even exacerbation of psychosis or suicidal behaviour. In fact, little is known
      about the differences between antipsychotic drugs in clinical practice, since
      only as few as 20% of patients may be eligible for studies comparing
      antipsychotic medications with each other. The aim of this study was to find out
      if the use of conventional antipsychotics is associated with an increased risk of
      akathisia (compared with atypical antipsychotics) even when low doses of
      conventional antipsychotics are used. The Barnes Akathisia Rating Scale was used
      to evaluate akathisia in 100 outpatients on antipsychotic medication.
      Conventional antipsychotics were associated with an increased risk of akathisia
      compared with atypical antipsychotics, although the chlorpromazine equivalent
      doses of conventional antipsychotics were lower than those of the atypicals. An
      additional akathisia-provoking effect of SSRIs could not be ruled out. The
      results suggest favouring atypical antipsychotic medication in patients who may
      easily develop akathisia.

PMID- 17454731
TI  - New AZT analogues having 5'-alkylsulfonyl groups: synthesis and anti-HIV
      activity.
AB  - New derivatives of azidothymidine (AZT) substituted by alkyl and alkylsulphonyl
      groups at N-3 and C-5', respectively, have been synthesized. The new synthesized
      derivatives showed remarkable anti-HIV-1 and HIV-2 activity in MT-4 cells.
      Compounds 8 and 10 have IC(50) values of 0.83 and 0.31 microg/mL against HIV-1
      with therapeutic index of 83 and 403, respectively, and IC(50) values of 0.93 and
      0.29 microg/mL against HIV-2 with therapeutic index of 74 and 431, respectively.
      This means that compounds 8 and 10 were cytotoxic to MT-4 cells at CC(50) of 69.2
      microg/mL and 125 microg/mL, respectively.

PMID- 17454732
TI  - Fluoroanalogues of anti-cytomegalovirus agent cyclopropavir: synthesis and
      antiviral activity of (E)- and (Z)-9-{[2,2-bis(hydroxymethyl)-3
      fluorocyclopropylidene]methyl}-adenines and guanines.
AB  - Synthesis of fluorinated cyclopropavir analogues 13a, 13b, 14a, and 14b is
      described starting from alkene 15. Addition of carbene derived from
      dibromofluoromethane gave bromofluoro cyclopropane 16. Reduction (compound 17)
      followed by desilylation gave intermediate 18, which was transformed to 2
      nitrophenylselenenyl derivative 19. Oxidation to selenoxide 20 was followed by
      beta-elimination to afford methylenecyclopropane 21. Addition of bromine provided
      compound 22 for alkylation-elimination of adenine and 2-amino-6-chloropurine. The
      resultant E,Z isomeric mixtures of methylenecyclopropanes 23a + 24a and 23c + 24c
      were resolved and the individual isomers were deprotected to give adenine
      analogues 13a and 14a as well as compounds 13c and 14c. Hydrolytic dechlorination
      of 13c and 14c furnished guanine analogues 13b and 14b. The only significant
      antiviral effects were observed with analogue 13a against HCMV and 14a against
      VZV in cytopathic inhibition assays.

PMID- 17454733
TI  - Preparation of potential cell-permeant nucleoside-2',3'-cyclic phosphate
      precursors.
AB  - Uridine-3'-phosphorothiolate triesters bearing lipophilic moieties were prepared
      via Michaelis-Arbuzov chemistry. Subsequent deprotection of the S-cholesteryl
      phosphorothiolate triester afforded the corresponding diester which underwent
      spontaneous Cyclization to cleanly afford uridine 2',3'-cyclic phosphate. This
      transesterification reaction could be expedited by treatment with iodine under
      mild, neutral conditions.

PMID- 17454734
TI  - Hypoxanthine-guanine phosphoribosyltransferase deficiency: biochemical and
      molecular findings in six Argentine patients.
AB  - Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is an inborn
      error of purine metabolism responsible for Lesch-Nyhan Disease (LND) and its
      partial phenotypes, HPRT-related hyperuricemia with neurologic dysfunction (HRND)
      and hyperuricemia alone. We report here the recognition of six Argentine
      patients, two with LND and four with HRND. All patients presented elevated
      excretion of uric acid, hypoxanthine, and xanthine and decreased HPRT enzyme
      activities <1 nmol/h/mg Hb. The molecular analysis demonstrated in the two LND
      patients a novel inherited transition mutation, c.203T >C (L68P), in one subject
      and a germline transition mutation, c.209G >A (G70E), in the other. In the HRND
      patients a novel transversion mutation, c.584 A >C (Y195S), was found in three
      related patients and an inherited transition mutation, c.143G >A (R48H), in the
      fourth subject.

PMID- 17454735
TI  - A novel universal linker for efficient synthesis of phosphorothioate
      oligonucleotides.
AB  - A versatile and conformationally preorganized universal linker molecule is
      reported here for efficient synthesis of phosphorothioate oligonucleotides. With
      respect to nucleoside loaded support, comparable yield and quality based on ion
      pair LC-MS are obtained for both deoxy and 2'-O-methoxyethyl modified
      phosphorothioate oligonucleotides. No 3'-phosphate or phosphorothioate monoester
      or any modification of universal molecule still attached to oligonucleotide was
      observed. [structure: see text]

PMID- 17454736
TI  - The fluoride cleavable 2-(cyanoethoxy)methyl (CEM) group as reversible 3'-O
      terminator for DNA sequencing-by-synthesis - synthesis, incorporation, and
      cleavage.
AB  - A new and promising sequencing technology called sequencing-by-synthesis (SBS)
      enables fast determination of DNA sequences. 2'-Deoxynucleotides containing the
      (2-cyanoethoxy)methyl (CEM) group at the 3'-O-position are potential reversible
      terminators for the SBS technology. Herein we describe the synthesis, the
      incorporation by several polymerases, and the cleavage of this 3'-O-blocking
      group using 3'-O-CEM-thymidinyl-5'-O-triphosphate 7 as an example.

PMID- 17454737
TI  - Selective photo-cross-linking of 2'-O-psoralen-conjugated oligonucleotide with
      RNAs having point mutations.
AB  - It has been reported that point mutations in genes are responsible for various
      cancers and the selective regulation of the gene expression is an important issue
      to develop a new type of anticancer drugs. In this report, we present a new type
      of antisense molecule that photo-cross-links to an oligoribonucleotide having a
      point mutation site in a sequence specific manner. 2'-O-psoralen-conjugated
      adenosine was synthesized in four steps from adenosine and introduced in the
      middle of an oligodeoxyribonucleotide (2'-Ps-oligo). Compared with 5'-O-psoralen
      conjugated oligodeoxyribonucleotide (5'-Ps-oligo), which has a psoralen at the 5'
      end, 2'-Ps-oligo more selectively photo-cross-linked to a pyrimidine base of the
      site of alteration from purine to pyrimidine in the oligoribonucleotide.

PMID- 17454738
TI  - Racemic synthesis and antiviral evaluation of 4'(alpha)-hydroxymethyl and
      6'(alpha)-methyl substituted apiosyl nucleosides.
AB  - This article reports the novel synthesis of substituted apiosyl nucleosides. The
      key apiosyl intermediate 9 was constructed by sequential ozonolysis, reductions,
      and acetylation from the ester derivative 6. The nucleosides of uracil, thymine,
      cytosine, and adenine were synthesized using the glycosyl condensation procedure
      (silyated base and TMSOTf). The antiviral activities of the synthesized compounds
      against the HIV-1, HSV-1, HSV-2, and HCMV viruses were evaluated. The adenine
      derivative 26 showed weak anti-HIV activity (EC(50) = 10.1 microg/ml) without
      exhibiting any cytotoxicity up to a concentration of 100 microM.

PMID- 17454739
TI  - Noncovalent interaction of G-quadruplex DNA with acridine at low concentration
      monitored by MALDI-TOF mass spectrometry.
AB  - The telomeric G-rich single-stranded DNA d(T(2)G(8)) can adopt in vitro G
      quadruplex structure, even at low DNA concentration. Studies on stability of
      telomeric structures, has gained importance recently as the molecules, which can
      stabilize quadruplex structure, can inhibit cancer progression. In this study, G
      quadruplex structure is formed by 1.0 mM NH(4)(I) ion. Stability of G-quadruplex
      complex is studied on interaction with acridine using CD and MALDI-TOF mass
      spectrometry. MALDI-TOF mass spectrometric experiments were carried out mainly to
      observe the noncovalent drug-DNA interactions at low concentration. From MALDI
      TOF spectrum, it is identified that three ammonium ions are required for the
      formation of G-quadruplex structure and to provide stability to NH(4)(I)-G
      quadruplex complex. With MALDI-TOF it is evident that two acridine molecules
      interact with NH(4)(I) G-quadruplex complex. CD studies, shows that stability of
      NH(4)(I) G-quadruplex, decreases and conformation change takes place on
      interaction with acridine. Interaction with drug reduces mostly due to
      transformation of G-quadruplex complex to single stranded DNA.

PMID- 17454740
TI  - Application of solid-phase chemistry for the synthesis of 3'-fluoro-3'
      deoxythymidine.
AB  - Reported solution-phase methods for the synthesis of 3'-fluoro-3'-deoxythymidine
      (FLT) are cumbersome, require purification of intermediates, and include several
      protecting/deprotecting steps. To circumvent these problems, a solid-phase
      strategy was designed for the synthesis of FLT. Thymidine was immobilized on
      trityl resin via the 5'-hydroxyl group. The subsequent mesylation of the free 3'
      hydroxyl group in the presence of methanesulfonyl chloride afforded the polymer
      bound 3'-O-mesylthymidine. Nucleophilic substitution of the mesyl moiety by
      hydroxyl group in the presence of sodium hydroxide produced the polymer-bound
      threothymidine. Fluorination with diethylaminosulfur trifluoride followed by
      acidic cleavage of the polymer-bound FLT in the presence of trifluoroacetic acid
      afforded FLT.

PMID- 17454741
TI  - Mitochondrial variant G4132A is associated with familial non-arteritic anterior
      ischemic optic neuropathy in one large pedigree.
AB  - OBJECTIVE: To identify the genetic factors associated with familial non-arteritic
      anterior ischemic optic neuropathy (NA-AION) in a large pedigree. METHODS: Eleven
      family members of a single pedigree, including six affected with NA-AION,
      underwent detailed clinical examinations. The mitochondrial DNA of the proband
      was sequenced in its entirety in search of disease-causing mutations associated
      with NA-AION in the pedigree. A control panel comprising 1488 patients suspected
      of having Leber hereditary optic neuropathy (LHON) and 97 general-population
      control subjects was screened for the mitochondrial sequence variant identified
      in the family. RESULTS: Affected family members were all male and exhibited
      classic features of NA-AION. Their mean age was 50.2 +/- 5.0 years. A total of 23
      sequence variations were detected in the mitochondrial genome of the proband,
      including one novel sequence variation (G4132A, Ala276Thr) in the NADH
      dehydrogenase subunit 1 gene (ND1). The G4132A mitochondrial variant was detected
      in six members of a single pedigree with NA-AION. The G4132A variation was not
      observed in any of the 1585 subjects in the control panel. Moreover, this variant
      was not identified in over 2469 ethnically diverse individuals previously
      evaluated through the Human Mitochondrial Genome Database. None of the three
      major mutations associated with LHON (G3460A, G11778A, T14484C) were identified
      in the family. CONCLUSION: The G4132A mitochondrial variation is associated with
      familial NA-AION in our pedigree.

PMID- 17454742
TI  - Attitudes regarding predictive testing for retinitis pigmentosa.
AB  - PURPOSE: To assess attitudes towards predictive testing for autosomal dominant
      retinitis pigmentosa (ADRP). METHODS: A prospective questionnaire study of 46
      affected adults and their adult family members identified from pedigrees clearly
      consistent with ADRP or who had had DNA-testing confirmation of ADRP before the
      study commenced. RESULTS: High proportions of unaffected siblings (73%) and
      patients (67%) agreed to prenatal testing. Patients agreed to prenatal testing.
      Patients agreed significantly more often than unaffected siblings that treatment
      should be available prior to initiating predictive testing. Psychoemotional
      distress was reported in 57% of the affected adults and their family members in
      recollecting their own predictive testing as children. CONCLUSIONS: ADRP families
      indicate a favorable attitude towards testing presymptomatic children with
      counseling to lessen the psychological and social impact of results.

PMID- 17454743
TI  - Molecular genetic analysis of a consanguineous south Indian family with
      congenital glaucoma: relevance of genetic testing and counseling.
AB  - The genetic background of congenital glaucoma in a consanguineous south Indian
      family was examined by homozygosity analyses. Significant evidence for the
      homozygosity of alleles was detected for markers D2S177 and D2S1346 that are
      tightly linked to the CYP1B1 gene, and further involvement of this gene was
      confirmed by the co-segregation of a novel truncating mutation (Q110X) in exon 2
      with the disease in all affected members. Newborn genetic screening and carrier
      identification were also performed in the family. The role of consanguinity and
      the risk of autosomal recessive disease were discussed and genetic counseling was
      given.

PMID- 17454744
TI  - Psychosocial adjustment to visual loss in patients with retinitis pigmentosa.
AB  - PURPOSE: To investigate psychosocial adjustment to visual loss in patients with
      retinitis pigmentosa (RP). DESIGN: Cross-sectional study. METHODS: Thirty-three
      legally blind patients with RP participated in the study. Information regarding
      the patients' adjustment to their visual loss was obtained using the
      Psychological Adjustment to Illness Scale (PAIS-SR). Seven psychosocial domains
      were tested: health-care orientation, vocational environment, domestic
      environment, sexual relationships, extended family relationships, social
      environment, and psychological distress. These scores were compared with the
      psychosocial adjustment of patients with diabetes. RESULTS: Significantly
      elevated scores (a high score reflecting poor adjustment) were seen in four out
      of seven domains. The highest relative score was seen in the health-care
      orientation domain (65 +/- 14, p < 0.001), followed by vocational function (61 +/
      11, p < 0.001), social environment (58 +/- 9, p < 0.001), and extended family
      relationships (55 +/- 9, p < 0.05). The total PAIS score was significantly
      elevated (58 +/- 8; p < 0.001). CONCLUSIONS: Patients with RP have difficulties
      in adjusting to their visual loss particularly with respect to health-care
      orientation, vocational environment, social environment, and extended family
      relationships. They face more difficulties in these domains than diabetic
      patients in adjusting to their illness.

PMID- 17454745
TI  - RRH, encoding the RPE-expressed opsin-like peropsin, is not mutated in retinitis
      pigmentosa and allied diseases.
AB  - Many genes from retinoid metabolism cause retinitis pigmentosa. Peropsin, an
      opsin-like protein with unknown function, is specifically expressed in apical
      retinal pigment epithelium microvilli. Since rhodopsin and RGR, another opsin
      like protein, cause retinitis pigmentosa, we used D-HPLC to screen for the
      peropsin gene RRH in 331 patients (288 with retinitis pigmentosa and 82 with
      other retinal dystrophies). We found 13 nonpathogenic variants only, among which
      a c.730_731delATinsG that truncates the last two transmembrane-spanning fragments
      and the Lys284 required for retinol binding, but does not segregate with the
      disease phenotype. We conclude that RRH is not a frequent gene in retinitis
      pigmentosa.

PMID- 17454746
TI  - No maternally inherited diabetes and deafness mutations in a sample of 193
      Tasmanian diabetics with glaucoma.

PMID- 17454749
TI  - Circulating nucleic acids in plasma/serum.
AB  - Since the discovery of circulating nucleic acids in plasma in 1948, many
      diagnostic applications have emerged. For example, diagnostic and prognostic
      potentials of circulating tumour-derived DNA have been demonstrated for many
      types of cancer. The parallel development of fetal-derived DNA detection in
      maternal plasma has opened up the possibility of non-invasive prenatal diagnosis
      and monitoring of many pregnancy-associated disorders. In this regard, non
      invasive fetal rhesus blood group genotyping has already been translated to
      clinical practice. Other applications of circulating DNA in traumatology and
      transplant monitoring have also been reported. The more recent discoveries of
      circulating tumour-derived RNA and fetal-derived RNA have proven to be equally
      important as their DNA counterparts. Successful prenatal diagnosis of Down's
      syndrome by fetal RNA analysis has recently been reported. However, the definite
      origin and release mechanisms of circulating nucleic acids have remained
      incompletely understood, with cell death being suggested to be associated with
      such nucleic acid release. Pre-analytical standardisation will become
      increasingly relevant when comparing data from different laboratories. In
      conclusion, studies of circulating nucleic acids have promised exciting
      developments in molecular diagnostics in the years to come.

PMID- 17454750
TI  - Lobular in situ neoplasia and columnar cell lesions: diagnosis in breast core
      biopsies and implications for management.
AB  - Histopathologists are encountering intra-lobular epithelial proliferations more
      frequently in core biopsies taken from lesions identified in mammographic breast
      screening programmes. In particular, columnar cell lesions are increasingly being
      seen in core biopsies taken for the histological assessment of mammographically
      detected microcalcifications. The morphological features of lobular neoplasia are
      relatively well known, but columnar cell lesions, particularly forms with
      atypical features, are less widely recognised. The biological and clinical
      significance of both of these intra-lobular processes is controversial, (1) as
      indicators of adjacent malignancy when encountered in core biopsy, (2) the
      relative risk conferred of development of subsequent malignancy, and (3) their
      precursor behaviour. For this reason, the optimal clinical management of these
      lesions, particularly when encountered on core biopsy, is unclear. This review
      provides an update on the histological diagnosis of lobular neoplasia and
      columnar cell lesions and outlines recent clinico-pathological and molecular
      findings with discussion on clinical management.

PMID- 17454752
TI  - The morphological spectrum of lymphadenopathy in HIV infected patients.
AB  - AIMS: To study the histological spectrum of lymphadenopathy in human
      immunodeficiency virus (HIV) infected Thai patients. METHODS: Lymph nodes from 55
      HIV infected patients were accessioned over a 19 month period in two pathology
      laboratories in Bangkok, Thailand. These were examined with H&E, Ziehl-Neelsen,
      periodic acid-Schiff (PAS), PAS with diastase (PAS/D), Gram and methenamine
      stains. RESULTS: Six reaction patterns were observed: (1) classic necrotising
      granulomas (30 cases); (2) extensive necrosis with minimal granulomatous response
      (5 cases); (3) sarcoid-like non-necrotising granulomas (5 cases); (4) foamy
      macrophage or pseudo-Gaucher cell response (5 cases); (5) inflammatory
      pseudotumour-like proliferation (3 cases); and (6) non-specific lymphoid
      hyperplasia (7 cases). Myriads of intracellular, long, slender acid-fast bacilli
      were found in those cases with the pseudo-Gaucher cell and inflammatory
      pseudotumour-like response, while variable numbers of bacilli were identified in
      those cases with non-necrotising sarcoid-like granulomas. Few scattered acid-fast
      bacilli were found in five cases with necrotising granulomas. In one case, yeast
      like organisms in keeping with Cryptococcus were identified. No organisms were
      identified in the cases showing lymphoid hyperplasia, extensive necrosis and
      minimal granulomatous response, and in the remaining cases of classic necrotising
      granulomas. CONCLUSIONS: The wide spectrum of histological changes in HIV
      associated lymphadenomegaly requires recognition, particularly as the majority
      were associated with acid-fast organisms, mostly in keeping with the
      morphological features of Mycobacterium avium-M. intracellulare complex that was
      distinctively stained by Grocott methenamine-silver, Gram and PAS stains. The
      histological changes mimic those of infarction and other infective lymphadenitis,
      sarcoidosis, Whipple's disease, inflammatory pseudotumour and spindle cell
      neoplasms.

PMID- 17454751
TI  - New evidence for geographic variation in the role of human papillomavirus in
      tonsillar carcinogenesis.
AB  - AIMS: Our previous studies of tonsillar cancers from New South Wales, Australia,
      and Jilin Province in the north-east of China, provided evidence that the
      proportion of these cancers attributable to human papillomavirus (HPV) varies
      geographically. This study provides the first data on HPV in tonsillar cancers
      from Hong Kong. METHODS: A total of 49 Hong Kong tonsillar cancers were analysed
      for HPV DNA by PCR/sequencing and for p16(INK4A), retinoblastoma (pRb) protein,
      cyclin D1 and p53 expression by semiquantitative immunohistochemistry as evidence
      of virus causality. Results were compared with those from New South Wales and
      Jilin Province. RESULTS: Of the 31 Hong Kong cancers with amplifiable DNA, nine
      (29%) were HPV positive by PCR compared with 46% from New South Wales and 0% from
      Jilin Province. HPV positivity correlated with female gender, young age, over
      expression of p16(INK4A) and loss of pRb and cyclin D1. Five-year disease
      specific survival for patients with HPV positive and HPV negative cancers was 82
      and 42%, respectively. Relationships between HPV status and cell protein
      expression in Hong Kong cancers were consistent with those from New South Wales
      and Jilin Province. The proportion of HPV-associated cancers reflected the
      relative incidence of oropharyngeal cancer in these regions. CONCLUSIONS: HPV is
      responsible for a small proportion of tonsillar cancers in Hong Kong patients.
      Differences in the proportions of tumours attributable to HPV in Hong Kong, New
      South Wales and Jilin Province may be due to environmental, cultural or genetic
      factors in the different populations.

PMID- 17454753
TI  - No difference in the occurrence of mismatch repair defects and APC and CTNNB1
      genes mutation in a multi-racial colorectal carcinoma patient cohort.
AB  - BACKGROUND AND AIMS: Colorectal cancers of different subtypes involve different
      pathogenic pathways like the Wnt and the mutator pathways. In this study, we
      screened 73 colorectal cancer cases from a multi-racial group for genetic and
      expression profile defects with the aim of correlating these with patients'
      clinicopathological characteristics. METHODS: Mutation screening of the entire
      coding region of APC and exon 3 of CTNNB1, loss of heterozygosity (LOH) of APC,
      and microsatellite instability (MSI) status were assessed for 44 patients with
      available paired frozen normal and tumour tissues. In addition, 29 cases with
      available paraffin embedded tumour blocks were screened for mutation in exon 3 of
      CTNNB1, the APC mutation cluster region (codon 1286-1513), and hMLH1, hMSH2,
      hMSH6 protein expressions by immunohistochemistry method. RESULTS: In our study,
      15/73 cases showed APC mutations (20.5%), 1/73 cases had CTNNB1 mutation (1.4%),
      5/32 cases had APC LOH (15.6%), and 16/70 (22.9%) cases revealed at least some
      form of mismatch repair (MMR) defect. Tumour grade (poor differentiation) was
      found to correlate significantly with right-sided tumour and mucinous histology
      (p = 0.01879 and 0.00320, respectively). Patients of younger age (below 45 years)
      more often had tumours of mucinous histology (p = 0.00014), while patients of
      older age (above 75 years) more often had tumours on the right side of the colon
      (p = 0.02448). Tumours of the mucinous histology subtype often had MMR defects (p
      = 0.02686). There was no difference in the occurrence of APC and CTNNB1 mutations
      and MMR defects found within our multi-racial colorectal cancer patient cohort.
      CONCLUSION: Our findings support the notion that racial factor may not be related
      to the occurrence of MMR defects and APC and CTNNB1 mutations in our multi-racial
      patient cohort.

PMID- 17454754
TI  - Mixed epithelial and stromal tumour (MEST) of the kidney: report of 14 cases with
      male and PEComatous variants and proposed histopathogenesis.
AB  - AIMS: This article adds new cases and variants of MEST with discussion of the
      histopathogenesis. METHODS AND RESULTS: Fourteen MEST were originally diagnosed
      as cystic nephroma which represents an incidence of 1.6% of renal neoplasms in
      adults. In females, the stromal component showed areas of mullerian
      differentiation with positive immunoreactivity for oestrogen (ER) and
      progesterone receptors (PR) and CD10. Immunoreactivity for HMB45 was identified
      in a single case having a leiomyomatous appearance. The epithelial component
      displayed features of mullerian epithelium and reactive renal tubular cells. In
      two male cases, MEST consisted of fibrous and smooth muscle stroma and cysts
      lined only by reactive renal tubular cells. Immunoreactivity for ER and PR was
      focal and weak. CONCLUSIONS: MEST represents a tumour developing from mullerian
      like stromal cells in the kidney. The neoplastic stroma encroaches on the renal
      tubules and has the potential to stimulate the growth of the renal tubules by
      contact, with development into cysts. Furthermore, the mullerian stroma likely
      induces the renal tubules to differentiate into mullerian-like epithelium.
      Melanocytic differentiation of the stroma may occur which represents the
      PEComatous variant. MESTs in males were histopathologically slightly different
      from those in females due to the different hormonal milieu.

PMID- 17454755
TI  - Ischaemic injury to femoral head induces apoptotic and oncotic cell death.
AB  - AIMS: The mechanism of cell death in ischaemic osteonecrosis of the femoral head
      is not clear. Therefore, this study was designed to clarify the mode of cell
      death following ischaemic osteonecrosis of the femoral head in an established pig
      model. METHODS: Morphological assessment, terminal deoxynucleotidyl transferase
      mediated dUTP nick end-labelling (TUNEL) assay, detection of DNA laddering and
      transmission electron microscopy studies were performed to determine whether
      apoptosis is one of the pathways of cell death following ischaemic osteonecrosis
      of the femoral head. RESULTS: Mode of cell death was investigated from 2 to 14
      days following the surgical induction of ischaemia. Ischaemic femoral heads
      showed morphological evidence of cell death by oncotic and apoptotic pathways in
      earlier stages of osteonecrosis. TUNEL positive cells were seen from 2 to 14 days
      following the induction of ischaemia. DNA samples obtained from ischaemic femoral
      heads following the induction of ischaemia showed nucleosomal ladders indicating
      apoptotic cell death. Electron micrographs also showed morphological changes
      associated with apoptosis. CONCLUSIONS: This study demonstrates that oncosis is
      not the sole mechanism of cell death following ischaemic injury of the femoral
      head. Both apoptosis and oncosis are involved as a result of ischaemic injury to
      the femoral head.

PMID- 17454757
TI  - D-dimer identifies stages in the progression of diabetes mellitus from family
      history of diabetes to cardiovascular complications.
AB  - AIM: The aim of the study was to ascertain whether there is variation in the
      fibrinolytic/coagulation component of diabetes associated with disease
      progression to macrovascular complications and whether D-dimer can discriminate
      such variation. METHODS: A total of 343 participants were selected based on
      clinical status and divided into 7 groups: control, family history of diabetes,
      pre-diabetes with/without CVD, diabetes with/without CVD and CVD only. Plasma D
      dimer was tested. Statistical analysis was performed on log normalised data by
      ANOVA, Fisher's LSD post hoc test. After the initial analysis, data were
      classified and re-analysed by quartiles, interquartile range and 95(th)
      percentile. RESULTS: An overall significant difference between groups (p<0.002)
      and a steady rise in D-dimer levels that became increasingly higher than control
      as the disease progressed from pre-diabetes to cardiovascular complications was
      observed. A statistically significant difference was observed between control
      versus diabetes (p<0.0005). Analysis of data by quartiles and percentiles gave
      qualitatively similar results, but a greater significant difference between
      control versus pre-diabetes at 3rd quartile and interquartile range (p<0.014).
      CONCLUSION: We report changes in D-dimer levels that may indicate diabetes
      disease progression to macrovascular complications. Using D-dimer in conjunction
      with other biomarkers to identify stages of disease progression, commencing from
      pre-diabetes and continuing to development of asymptomatic and clinical
      cardiovascular disease in diabetes mellitus, is worthy of consideration.

PMID- 17454756
TI  - A histological survey of green fluorescent protein expression in 'green' mice:
      implications for stem cell research.
AB  - AIMS: The transgenic enhanced green fluorescent protein (EGFP) expressing 'green'
      mouse (C57BL/6-TgN(ACTbEGFP)1Osb) is a widely used tool in stem cell research,
      where the ubiquitous nature of EGFP expression is critical to track the fate of
      single or small groups of transplanted haematopoietic stem cells (HSC). Our aim
      was to investigate this assumed ubiquitous expression by performing a detailed
      histological survey of EGFP expression in these mice. METHODS: Fluorescent
      microscopy of frozen tissue sections was used to perform a detailed histological
      survey of the pattern of EGFP expression in these mice. Flow cytometry was also
      used to determine the expression pattern in blood and bone marrow. RESULTS: Three
      patterns of EGFP expression were noted. In most tissues there was an apparently
      stochastic variegation of the transgene, with individual cell types demonstrating
      highly variable rates of EGFP expression. Certain specific cell types such as
      pancreatic ductal epithelium, cerebral cortical neurones and glial cells and
      glomerular mesangial cells consistently lacked EGFP expression, while others,
      including pancreatic islet cells, expressed EGFP only at extremely low levels,
      barely distinguishable from background. Lastly, in the colon and stomach the
      pattern of EGFP expression was suggestive of clonal inactivation. Only cardiac
      and skeletal muscle showed near ubiquitous expression. CONCLUSIONS: These
      findings raise questions regarding the 'ubiquitous' expression of EGFP in these
      transgenic mice and suggest caution in relying overly on EGFP alone as an
      infallible marker of donor cell origin.

PMID- 17454758
TI  - Antineutrophil cytoplasmic antibody measurement: advantages and disadvantages of
      a capture PR3 ELISA and a direct PR3 ELISA.
AB  - AIM: To compare the performance of a capture proteinase 3 enzyme linked
      immunosorbent assay (PR3 ELISA) with a direct PR3 ELISA in the measurement of PR3
      antineutrophil cytoplasmic antibodies (ANCA). METHOD: The performance of both
      assays systems was compared using two sets of sera. Sera from patients (n = 49)
      suffering from Wegener's granulomatosis (WG) and fulfilling the American College
      of Rheumatology classification criteria (or a modification of those criteria that
      allowed for ANCA positivity) were used along with sera from a group of patients
      (n = 48) considered to have a clinically false positive PR3 ANCA result when
      measured by routine direct ELISA. RESULTS: Using the assay specific cut-offs, the
      direct ELISA gave a positive result in 92% on repeat testing and the capture
      ELISA a positive result in 84% of sera from patients with WG. The capture ELISA
      was negative in 75% of patients considered to have a false positive PR3 ANCA on
      initial testing by direct ELISA (27% were negative on repeat testing by direct
      ELISA). The mean concentration of PR3 ANCA in WG patient sera measured by the
      capture ELISA was significantly higher than that measured by the direct ELISA.
      The capture PR3 ELISA had a broader analytical range which was also reflected in
      PR3 ANCA concentrations measured in serial serum samples from WG patients.
      CONCLUSION: In this study the direct PR3 ELISA performed better as a screening
      test for PR3 ANCA compared with the capture PR3 ELISA, mainly because the cut-off
      for the capture ELISA needed to be set higher to avoid non-specific binding. In
      contrast, the improved analytical range of the capture ELISA made it a
      potentially more useful method for monitoring serial PR3 ANCA concentrations. In
      specific serum samples the capture ELISA was better able to discriminate 'false
      positive' PR3 ANCA.

PMID- 17454759
TI  - An adult with lung nodules and renal mass: diagnosis on cytology.

PMID- 17454760
TI  - Ductal carcinoma in situ arising in an epithelial inclusion within an axillary
      lymph node.

PMID- 17454761
TI  - Endobronchial metastatic breast carcinoma clinically, histologically and
      cytologically mimicking pulmonary small cell carcinoma.

PMID- 17454762
TI  - Stress response in mouse brain after long-term (2 year) exposure to mobile
      telephone radiofrequency fields using the immediate early gene, c-fos.

PMID- 17454763
TI  - Primary chordoma of the nasal cavity: a rare site of presentation.

PMID- 17454764
TI  - Aberrant diffuse expression of synaptophysin in a sinonasal alveolar
      rhabdomyosarcoma.

PMID- 17454765
TI  - Dedifferentiated chordoma with rhabdomyoblastic differentiation.

PMID- 17454766
TI  - Chondroid chordoma of the thoracic spine: case report.

PMID- 17454767
TI  - Menetrier's disease in a patient with ulcerative colitis: a case report and
      review of the literature.

PMID- 17454768
TI  - Gonadoblastoma progressing to dysgerminoma in a 55-year-old woman with normal
      karyotype.

PMID- 17454769
TI  - Unilateral pelvic endometriosis and congenital unilateral ovarian agenesis.

PMID- 17454770
TI  - Gelatinous transformation of bone marrow in acquired immunodeficiency syndrome.

PMID- 17454771
TI  - Acute selenium toxicity: Australia's second fatality.

PMID- 17454772
TI  - Hereditary protein C deficiency: a case report.

PMID- 17454774
TI  - Current diagnosis of inherited bone marrow failure syndromes.
AB  - Prompt and accurate diagnosis is required for optimal treatment and genetic
      counseling of patients with inherited bone marrow failure syndromes (IBMFS).
      However, the diverse clinical picture of these syndromes and their rareness is
      often associated with diagnostic difficulties. Recently, an improved diagnostic
      approach is possible by the cloning of many of the causative genes. Fanconi
      anemia (FA) patients belong to at least 12 complementation groups, of which 11
      genes have been cloned. An approach combining an induced chromosomal breakage
      test, detection of FANCD2-L by Western blot analysis, complementation group
      analysis, and detailed mutation analysis enables unraveling the causative
      mutation in the majority of patients. With the use of such strategies,
      genotype/phenotype correlations in FA are evolving. In dyskeratosis congenita
      mutations in DCK1, TERC, and TERT genes have been identified, but mutations have
      been found in less than half of these patients. In patients with Shwachman
      Diamond syndrome, mutations in the SBDS gene were found in approximately 90% of
      patients. In Diamond-Blackfan anemia the RSP19 gene is mutated in 20-25% of
      patients. Heterozygote ELA2 mutations are found in 60-80% of severe congenital
      neutropenia patients. All patients with congenital amegakaryocytic
      thrombocytopenia have mutations in the thrombopoietin receptor gene c-Mpl.

PMID- 17454776
TI  - Serum VEGF as a significant marker of treatment response in hodgkin lymphoma.
AB  - This pilot study aimed at determining serum VEGF levels (S-VEGF) at diagnosis and
      at restaging in children with Hodgkin lymphoma, and investigating whether this
      parameter provides prognostic information for remission after 2 courses of
      chemotherapy. PET-CT fusion was performed to assess response to treatment.
      Changes in S-VEGF levels were found to correlate with response to treatment for
      most of the children. This provides a rationale for exploring clinical interest
      in S-VEGF measurements in a larger group of children with Hodgkin lymphoma, and
      using the test for clinical trials of anti-angiogenic therapies.

PMID- 17454775
TI  - Almost normal cognitive function in patients during therapy for childhood acute
      lymphoblastic leukemia without cranial irradiation according to ALL-BFM 95 and
      COALL 06-97 protocols: results of an Austrian-German multicenter longitudinal
      study and implications for follow-up.
AB  - In a multicenter study the authors prospectively investigated neurocognitive
      function in childhood ALL patients. Sixty-six patients (mean age at diagnosis 7.9
      +/- 3.6 years, 34 female), treated with repeated intrathecal and systemical
      methotrexate administrations without cranial irradiation, underwent psychometric
      testing for intelligence, concentration, and visual-motor integration
      postdiagnosis and after reinduction therapy. Although there was a statistically
      significant decline of intellectual function after reinduction therapy for
      younger patients and girls (IQ scores still within normative data range), there
      were no differences in visual-motor performance and concentration over the time
      of induction therapy. Thus, neurocognitive examination should focus on younger
      ALL patients and girls.

PMID- 17454777
TI  - Control of bleeding associated with hemophagocytic syndrome in children: an audit
      of the clinical use of recombinant activated factor VII.
AB  - This paper presents 2 cases of hemophagocytic lymphohistiocytosis (HLH) in whom
      recombinant factor VIIa (rFVIIa) was used for the management of hemorrhage. Both
      patients were diagnosed as HLH and were bleeding from the gut, which could not be
      controlled. Patients received rFVIIa at total doses of between 90 and 180
      microg/kg body weight. Hemostatic affect was achieved in both of the patients but
      lasted only a short time. The response was achieved after 1 h of administration
      of rFVIIa, lasting for 24 h. The use of rFVIIa was well tolerated. These 2
      patients suggest that rFVIIa is a beneficial agent in the management of
      hemorrhage in patients with HLH, although for a permanent homeostasis the control
      of primary disease is essential.

PMID- 17454778
TI  - Rhabdoid tumor of the kidney presenting with hemiplegia: report of a case.
AB  - Rhabdoid tumor of the kidney (RTK) is a rare and highly malignant neoplasm of
      infancy, with a strong tendency for early metastasis to distant regions. RTK is
      unique in its significant association with primary or metastatic brain tumors.
      The authors report the first case of RTK presenting initially with hemiplegia.
      The patient was found thereafter to have RTK concurrent with pulmonary
      metastases, a brain tumor, and a cerebral ischemic lesion. Intensive chemotherapy
      consisting of carboplatin and etoposide alternating with cyclophosphamide was
      unsuccessful and the patient died 5 months later because of severe respiratory
      distress resulting from widespread pulmonary metastases.

PMID- 17454779
TI  - An unusual case of reactive lymphocytosis mimicking acute leukemia.
AB  - The diagnosis of acute leukemia is based on a combination of clinical,
      hematological, morphological, cytogenetic, and immunophenotypic data. The authors
      report a case of reactive lymphocytosis with extremely elevated lymphocytic and
      lymphoblastic leukocytosis that mimicked acute lymphoblastic leukemia, not only
      morphologically, but also in immunophenotypic analysis. They could not determine
      any underlying disease marker other than infectious symptoms that were present
      for 20 days prior to presentation to their clinic. Although this case presented
      with extremely high lymphocytic leukocytosis, the patient had normal blood cell
      lineage, a moderate level of blastic cells in bone marrow, and normal physical
      findings. These findings convinced the authors to follow up the patient before
      beginning treatment.

PMID- 17454780
TI  - Maintenance immunotherapy by repetitive low-dose donor lymphocytes infusions in a
      child with relapse state aml after allogeneic stem cell transplantation.
AB  - The treatment of a child with a relapsed state acute leukemia after allogeneic
      stem cell transplantation (allo-SCT) is a challenge. The authors report about a
      child with an acute myelogenous leukemia (AML), which relapsed after allo-SCT
      despite immunological intervention. It was further treated with a second line
      chemotherapy followed by an infusion of stem cells and donor lymphocytes. Because
      of an immense risk for a further relapse, an immunological maintenance therapy
      was also performed, consisting of repetitive infusions of low doses of donor
      lymphocytes combined with low-dose chemotherapy. Presently, the child is in
      continuous complete remission and has a good quality of life.

PMID- 17454781
TI  - Myeloid sarcoma presenting with bilateral proptosis and kidney infiltration.
AB  - The authors describe a male infant with a history of transient pancytopenia who
      developed progressive bilateral proptosis associated with diffuse infiltration of
      the kidney and normal bone marrow. The histopathological examination of the
      kidney revealed diffuse infiltration of cells of myeloid origin with monocytic
      differentiation. Although orbital involvement by myeloid sarcoma, with or without
      concurrent acute myeloid leukemia, is well known, there are distinctive features
      in this patient that are not reported in the literature, namely bilateral
      proptosis and simultaneous presence of bilateral kidney infiltration, which
      enabled diagnosis.

PMID- 17454782
TI  - Kluver-Bucy syndrome in a boy with non-Hodgkin lymphoma.
AB  - Kluver-Bucy syndrome is a rare neurobehavioral condition characterized by visual
      agnosia, excessive oral tendency, hypermetamorphosis, placidity, altered sexual
      behaviors, and changes in dietary habits. The authors report a case of Kluver
      Bucy syndrome in a 10-year-old boy with non-Hodgkin lymphoma after intratechal
      methotrexate administration. He was treated by risperidone without any sequels.

PMID- 17454783
TI  - Pelvic alveolar rhabdomyosarcoma with bone marrow involvement misdiagnosed as
      acute myeloid leukemia.

PMID- 17454786
TI  - In vitro effects of growth factors and interferon-alpha on busulfan cytotoxicity.
AB  - An experimental approach to increasing the effectiveness of leukemia treatment
      with S-phase-specific cytotoxics is to increase the cycling of leukemia cells
      with growth factors. However, growth factors may have a different relationship
      with non-cell-cycle-specific agents. The authors examined the effects of
      granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony
      stimulating factor (GM-CSF), and interferon-alpha (INF-alpha) on the cytotoxic
      effects of the alkylating agent busulfan on the erythro-myeloid cell line K562. G
      CSF and GM-CSF increased the proliferation and colony-forming ability of K562
      cells and protected the cells from busulfan effects. INF-alpha decreased the
      colony-forming ability and proliferation of the K562 cells and demonstrated a
      possibly additive effect with busulfan. In the cell line K562, the growth factors
      G-CSF and GM-CSF protected the cells from the non-cell-cycle-specific alkylating
      agent busulfan, whereas IFN-alpha demonstrated an additive cytotoxic effect.

PMID- 17454787
TI  - Role of myeloid human cytomegalovirus infection in children's idiopathic
      thrombocytopenic purpura.
AB  - This project explores the specificity of myeloid human cytomegalovirus (HCMV)
      infection in pathogenesis of idiopathic thrombocytopenic purpura (ITP). Eighty
      one subjects with ITP were observed. HCMV early antigen and related myeloid cells
      in bone marrow, and platelet, HCMV IgM, and IgG in blood were tested. The results
      presented potent evidence that myeloid HCMV infection is a specific factor in
      children's ITP: patients of ITP with myeloid HCMV infection had a tendency for
      exacerbation, refractoriness, and chronic advance. However, HCMV did not affect
      the quantity of megakaryocyte, which showed the complicated relationships between
      HCMV and ITP.

PMID- 17454785
TI  - Pulmonary hypertension in sickle cell disease: relevance to children.
AB  - Pulmonary arterial hypertension (PAH), once considered a rare complication of
      sickle cell disease (SCD) and thalassemia, appears to be more common in adults
      with hemoglobinopathy than previously appreciated. On prospective screening of
      adults with SCD, approximately one-third of adults are found on echocardiography
      to have a tricuspid regurgitant jet velocity (TRV) of 2.5 m/s or higher, many of
      whom are asymptomatic. Dyspnea on exertion is the most common presenting symptom.
      This TRV abnormality is a marker for approximately 40% 3-year mortality in
      adults, and it is associated with laboratory values suggestive of more severe
      intravascular hemolysis. Release of hemoglobin and arginase from lysed red cells
      causes scavenging of nitric oxide (NO) and catabolism of L-arginine, the obligate
      substrate for NO synthase. The resulting impairment in NO bioavailability is
      associated with pulmonary vasoconstriction, endothelial dysfunction, thrombosis,
      and eventual development of plexogenic arterial lesions, the histological
      hallmark of all forms of PAH. Undoubtedly, additional pathophysiological
      mechanisms will also play a role in its multifactorial pathogenesis. Early data
      from children with SCD indicate a similar prevalence of elevated TRV, but the
      prognostic implications of this remain to be established. Individual patient
      diagnosis of PAH requires confirmation by right heart catheterization studies and
      individualized management. Hemolysis-associated PAH with impairments in NO
      bioavailability is being identified in thalassemia and other hemolytic disorders,
      and may be a general consequence of long-standing, severe intravascular hemolytic
      anemia.

PMID- 17454788
TI  - Nitric oxide affects serum ferritin levels in children with iron deficiency.
AB  - In iron deficiency, serum levels of ferritin decrease. The lack of iron has been
      thought to be the main factor in this decrease, but another potential factor is
      nitric oxide, which has been shown to affect ferritin metabolism in vitro. The
      aim of this study was therefore to evaluate in children with iron deficiency the
      relation of serum ferritin, nitric oxide degradation products (nitrate and
      nitrite), and endothelin-1, a protein closely related to nitric oxide function. A
      total of 80 children were included in the study (39 with iron deficiency, 41
      controls). Serum levels of ferritin, nitrate, nitrite, and endothelin-1 were
      measured in all participants. In children with iron deficiency, nitrate and
      nitrite levels were significantly higher (p < .009 and .01, respectively). Also,
      serum ferritin was negatively correlated with serum levels of nitrate and nitrite
      (p = .034, r = -.254 for nitrate and p = .01, r = -.593 for nitrite). No
      statistical relationship was found between serum ferritin and endothelin-1.

PMID- 17454789
TI  - Biphenotypic extramedullary blast crisis as a presenting manifestation of
      Philadelphia chromosome-positive CML in a child.
AB  - A 14-year-old child presented with generalized lymphadenopathy and massive
      hepatosplenomegaly. Peripheral smear and bone marrow examination were suggestive
      of Ph' positive chronic myeloid leukemia (CML) in chronic phase. However, lymph
      node biopsy showed extramedullary blast crisis with evidence of myeloid and T
      cell markers in blasts. Reverse transcriptase-polymerase chain reaction from
      lymph node aspirate revealed transcript for bcr-abl p210. Thus, we present here a
      unique case of childhood CML with extramedullary biphenotypic blast crisis
      (myeloid/T cell type) at initial presentation with bone marrow remaining in
      chronic phase. This case provides further evidence to the highly heterogeneous
      presentation of CML.

PMID- 17454790
TI  - Homozygous 23-bp insertion of endothelial protein c receptor gene in a child with
      fatal sepsis.
AB  - Endothelial protein C receptor (EPCR) is primarily localized on the endothelial
      cells of large blood vessels and is very low or absent in the microvascular
      endothelium of most tissues. EPCR augments the thrombin/thrombomodulin-dependent
      activation of protein C by 5- to 20-fold. EPCR appears to be physiologically
      significant in the control of blood coagulation and inflammation and in the host
      response to gram-negative sepsis. Here, the authors report an 8-month-old boy,
      who had chronic liver disease due to undetermined cause. He had Staphylococcus
      aureus and Candida albicans sepsis and died due to gastrointestinal, lung, and
      peritoneal bleeding during follow-up. Serum soluble EPCR level of the patient was
      high (225 ng/mL) during sepsis. A homozygous 23-bp insertion of EPCR gene was
      demonstrated. This case indicates the importance the EPCR gene plaus in pediatric
      sepsis. Homozygous 23-bp insertion of the EPCR gene may be associated with a
      tendency to sepsis and poor outcome.

PMID- 17454791
TI  - Is it safe to avoid bone marrow examination in suspected itp?
AB  - Two children with suspected ITP are described. One child was treated outside with
      corticosteroids and was diagnosed acute lymphoblastic leukemia. Another child was
      fresh and diagnosed as acute myeloid leukemia on bone marrow aspirate
      examination. Both the children had no physical or peripheral smear finding
      suggestive of leukemia. We suggest that a bone marrow examination is required in
      developing countries for evaluation of thrombocytopenia before labeling it an
      immune thrombocytopenic purpura.

PMID- 17454792
TI  - Clinical, radiological, and pathological findings in four children with
      gastrointestinal stromal tumors of the stomach.
AB  - The incidence of gastrointestinal stromal tumors (GISTs) in children is
      exceptionally low. However, during the last decade these tumors attracted
      increasing attention, because they were found to express the cell surface
      transmembrane receptor kit (CD117) that has tyrosine kinase activity. This
      tyrosine kinase can be semi-selectively inhibited by signal transduction
      inhibitors such as imatinib mesylate (Glivec), which is a competitive inhibitor
      of c-kit, c-abl, platelet-derived growth factor receptor-alpha (PDGFR-alpha) and
      PDGFR-beta, and abl-related gene (arg). The authors present the clinical,
      radiographic, and pathological findings of 4 children who were diagnosed with
      gastric GIST. One of them had an incomplete Carney triad including GIST and
      mediastinal paraganglioma. All 4 patients presented with anemia and anemia
      related symptoms and underwent total resection of the tumor. One patient received
      additional chemotherapy (in the pre-imatinib era) and 2 patients received a short
      course of imatinib mesylate. With a follow-up of 116, 55, 23, and 10 months all
      patients are alive in first complete continuous remission. In children and
      adolescents, particularly in female patients, GISTs should be included in the
      differential diagnosis of anemia secondary to gastrointestinal hemorrhage.
      Complete surgical resection is the mainstay of treatment for this tumor, with
      imatinib mesylate restricted to patients with advanced or metastatic tumors.
      Since late recurrences (up to 30 years following initial diagnosis) are reported,
      a life-long follow-up is mandatory in these patients.

PMID- 17454793
TI  - Clinical and epidemiological characteristics of retinoblastoma: correlation with
      prognosis in a Turkish pediatric oncology center.
AB  - Advanced intraocular tumors and metastatic disease in retinoblastoma patients
      still occur frequently in developing countries. The aim of this retrospective
      study was to describe the clinical and epidemiological characteristics of
      patients with retinoblastoma and the effects of these features on disease
      prognosis in the authors' pediatric oncology unit as a developing country profile
      to define the problem. A retrospective chart review of 91 patients who presented
      to the unit between May 1996 and December 2003 was conducted in this study.
      Patients with unilateral disease presented at a median age of 24 months and those
      with bilateral disease at a median age of 9.5 months (p < .01). Most of the eyes
      with retinoblastoma (68.6%) had Reese-Ellsworth stage V disease. Metastatic
      disease was diagnosed in 19 (20.9%) patients. Cases with metastatic disease
      presented at a median age of 24 months and those without metastatic disease at a
      median age of 12.5 months (p < .05). In 31 patients (34.1%) there was a delay in
      diagnosis. The enucleation ratio in eyes with advanced intraocular stage was
      significantly higher than in eyes with early intraocular stage (57.9 vs. 3.8%) (p
      < .001). In patients with metastatic disease, tumor recurrence was more frequent
      than in the nonmetastatic patients (36.8 vs. 4.2%) (p < .01). Seven children
      (7.7%) died due to central nervous system (CNS) metastasis (p < .01). Advanced
      intraocular disease and distant metastases occur more frequently in Turkish
      children with retinoblastoma than in children in developed countries, causing a
      higher rate of enucleation and mortality. Late referral might account for the
      delayed diagnosis.

PMID- 17454794
TI  - Coagulopathy after spider bites to a 6-year-old boy.

PMID- 17454795
TI  - Satisfaction with outpatient physiotherapy: focus groups to explore the views of
      patients with acute and chronic musculoskeletal conditions.
AB  - Patient satisfaction is generally regarded as an important component in quality
      health care. However, there has been little satisfaction research in
      physiotherapy compared with that in other clinical fields with few qualitative
      studies that have explored patients' perceptions and attitudes toward
      physiotherapy. We report on the use of focus groups, as part of a multimethod
      approach of qualitative data collection into patients' satisfaction with their
      outpatient physiotherapy within the NHS system of care in the United Kingdom. We
      explored the factors that affect patients' satisfaction with musculoskeletal
      outpatient physiotherapy. A purposeful sample of patients with acute and chronic
      musculoskeletal patients who had been discharged from physiotherapy within the
      previous 4 months was drawn from both an inner city and suburban hospital. Two
      acute groups (n = 4, n = 10) and two chronic groups (n = 5, n = 11) were
      convened. A topic guide drew on themes that had emerged from the earlier
      qualitative phases of the study and guided the discussion in relation to
      pretreatment, treatment, and outcome stages of physiotherapy care. Sessions were
      tape-recorded, transcribed, and content was analyzed to code and categorise the
      primary patterns in the data. Although subjects in both the acute and chronic
      groups expected that treatment would improve their symptoms and function, they
      differed in the degree to which they perceived that this was achieved. Both
      satisfactory and unsatisfactory aspects of care emerged under the principal
      themes of expectations, communication, perceptions of the therapist, treatment
      process, and outcome. Those in the acute group were optimistic of a good result,
      whereas those with chronic degenerative conditions were either doubtful of
      improvement or unrealistic in their hopes for complete resolution of their
      symptoms. It was also apparent that subjects could be further divided into one of
      three groups (positive, negative, ambivalent), depending on the degree to which
      they perceived their needs and expectations had been met. Verbatim comments are
      presented to illustrate the spectrum of views expressed. The therapeutic
      encounter between therapist and patient is complex and reflects the
      multidimensional construct of satisfaction. Focus groups were used in this study
      as part of a multimethod approach into patient satisfaction with outpatient
      physiotherapy; they provided additional valuable insight into the reasoning
      process behind patients' evaluation of their care. Establishing patients' needs,
      particularly the extent to which these might be psychosocial rather than
      physical, could point the way to a more patient-focussed and productive
      physiotherapy experience. Although rich in-depth information was obtained from
      this study, caution should be applied in generalizing the findings because of the
      small sample sizes and the setting of the study within the NHS system of care.
      Therefore, further work to identify the full spectrum of issues relating to
      patients' satisfaction with their outpatient care is indicated.

PMID- 17454796
TI  - Satisfaction with outpatient physiotherapy: a survey comparing the views of
      patients with acute and chronic musculoskeletal conditions.
AB  - Patient satisfaction is a complex construct and is regarded as an important
      component in the assessment of care quality. Investigations into patient
      satisfaction with care have steadily increased across a range of specialties over
      the last three decades, but there has been a paucity of studies into satisfaction
      with physiotherapy. The limitations of previous instruments used to examine
      satisfaction with outpatient (OP) physiotherapy suggested the need for a new
      tool. The aim of the survey was to examine the level of satisfaction that
      patients with acute and chronic musculoskeletal conditions have with their
      physiotherapy outpatient treatment within the NHS system of care in the UK.
      Questionnaires were mailed to 420 patients with acute and chronic musculoskeletal
      conditions who had recently completed a course of OP physiotherapy. The 38-item
      self-completion questionnaire comprised six subscales; Expectation,
      Communication, Therapist, Organisation, Outcome, and Satisfaction, scored on a
      five-point Likert scale. Data were analysed by using SPSS Release 10 for Windows
      for frequency distribution of scores and regression analysis for factors
      predictive of satisfaction. The response rate was 66%. Results showed that
      patients were generally satisfied with the interpersonal, technical, and
      organisational aspects of care, although there was lower satisfaction with the
      clinical outcome in both groups. Organisational issues were the key determinants
      of satisfaction for the whole sample and the chronic group, with the therapist as
      key determinant for the acute group. Patient satisfaction surveys conducted as
      part of a continuous quality improvement programme are particularly important in
      providing therapists with feedback from patients about their experiences of
      physiotherapy services. This study has successfully used a new questionnaire to
      examine patients' satisfaction with outpatient physiotherapy in the United
      Kingdom. Further studies are now needed to validate the new questionnaire so that
      it can be incorporated into general physiotherapy practice as part of a regular
      audit programme.

PMID- 17454797
TI  - Patient expectations of physiotherapy: definitions, concepts, and theories.
AB  - Expectations are an integral part of the psychosocial makeup of each patient, and
      there is a growing recognition among physiotherapists that psychosocial issues
      may impact the outcome of physiotherapy. This article seeks to clarify the term
      "patient expectation" by providing some definitions and an overview of the
      literature describing the concepts and theories associated with patients'
      expectations. These concepts are then related to physiotherapy to highlight the
      impact that patients' expectations may have on the outcome of physiotherapy, and
      the implications for physiotherapy are discussed.

PMID- 17454798
TI  - Factors important for good interaction in physiotherapy treatment of persons who
      have undergone torture: a qualitative study.
AB  - Torture can be defined as the deliberate or systematic infliction of physical or
      mental suffering to force another person to yield information, as a punishment or
      to destroy a person's identity. The aim of the physiotherapy treatment for
      persons who have undergone torture is to relieve or reduce pain, correct
      musculoskeletal dysfunctions, teach the client to cope with pain, and regain body
      awareness. A good interaction and communication with each refugee is needed to
      optimize the treatment. The aim of this study was to identify factors important
      for a good interaction between physiotherapist (PT) and the patient among PTs
      specialising in refugees who have been tortured. A qualitative multiple case
      study was done. Ten physiotherapists working within the Red Cross, psychiatry or
      primary health care, who held positions specialising in treating persons who have
      undergone torture were interviewed. The interviews were analysed with content
      analysis. The results showed that the factors important for a good interaction
      could be summarised into two themes; prerequisites for a good interaction and
      interaction factors. Five prerequisites for a good interaction with persons who
      have undergone torture were found: personal characteristics, professional and
      therapeutic competence and support, language factors, time, and frames. Five
      factors in the interaction situation were important for a good interaction:
      cultural factors, treatments tailored to the patient's needs, to develop
      confidence and trust, religious factors, and capacity to handle negative
      emotions. All these factors have to be considered to improve the interaction
      between PTs and persons who have undergone torture.

PMID- 17454799
TI  - Effect of analgesic nerve block electrical stimulation in a patient with adhesive
      capsulitis.
AB  - Although the pathophysiology of adhesive capsulitis is poorly understood, the
      primary goal of therapeutic intervention is to restore pain-free, functional
      range of motion (ROM) of the shoulder. Pain and muscle guarding, particularly of
      the subscapularis muscle, are common impairments that occur with adhesive
      capsulitis. The purpose of this case report is to describe a novel approach to
      help the pain-muscle guarding-pain cycle associated with pain and limited
      shoulder motion in a patient with a medical diagnosis of adhesive capsulitis. The
      patient was a 64-year-old female with adhesive capsulitis. Outcome variables were
      the Shoulder Pain and Disability Index (SPADI), internal rotation (IR) and
      external rotation (ER) ROM, and rotational lack. Twelve treatments of moist heat,
      analgesic nerve block electrical stimulation, contract/relax exercises for
      shoulder IR/ER, and Pendulum/Codman exercises were administered. After both 2 and
      4 weeks of treatment, the patient demonstrated marked improvements in all areas.
      Overall, there was a 78-106% increase in ROM (IR and ER) and a 50-83% improvement
      in functional mobility (rotational lack & SPADI). It appears that analgesic
      electrical stimulation may have helped decrease the pain-muscle guarding cycle
      associated with adhesive capsulitis to enhance functional outcomes in a timely
      manner.

PMID- 17454800
TI  - Blast-related injuries from terrorism: an international perspective.
AB  - Terrorism using conventional weapons and explosive devices is a likely scenario
      and occurs almost daily somewhere in the world. Caring for those injured from
      explosive devices is a major concern for acute injury care providers. Learning
      from nations that have experienced conventional weapon attacks on their civilian
      population is critical to improving preparedness worldwide. In September 2005, a
      multidisciplinary meeting of blast-related injury experts was convened including
      representatives from eight countries with experience responding to terrorist
      bombings (Australia, Colombia, Iraq, Israel, United Kingdom, Spain, Saudi Arabia,
      and Turkey). This article describes these experiences and provides a summary of
      common findings that can be used by others in preparing for and responding to
      civilian casualties resulting from the detonation of explosive devices.

PMID- 17454801
TI  - Secondary triage: early identification of high-risk trauma patients presenting to
      non-tertiary hospitals.
AB  - OBJECTIVE: We sought to identify a combination of highly specific clinical
      variables that could be used to quickly identify a subset of high-need injured
      patients initially presenting to non-tertiary hospitals. METHODS: This was a
      retrospective cohort analysis of all injured adults 15 years or older meeting
      state trauma criteria, presenting to one of 42 non-tertiary hospital emergency
      departments (EDs) from January 1, 1998, through December 31, 2003, and surviving
      to ED disposition. The outcome included measures of timely resource need: early
      mortality (within 3 days of ED presentation), major nonorthopedic surgery within
      3 days, or intensive care unit stay 2 days or longer. RESULTS: A total of 12,183
      persons were included in the analysis, of which 3,643 (30%) patients had one or
      more of the outcome measures. The variables of greatest importance in identifying
      high-risk injured adults included (in order or priority): emergent airway
      intervention (prehospital or ED), initial ED GCS less than 11, ED blood
      transfusion, initial ED SBP less than 100 or more than 220 mmHg, and initial ED
      RR less than 10 or more than 32. These five variables had high specificity
      (89.1%, 95% confidence interval [CI] 88.2%-89.9%) in identifying 37.9% (95% CI
      35.0%-40.7%) of high-risk trauma patients presenting to non-tertiary facilities.
      The positive likelihood ratio (+LR) for early mortality/early resource need
      increased for patients with one or more (+LR 3.5), two or more (+LR 9.1), and
      three or more (+LR 16.2) of the five risk criteria. CONCLUSIONS: There are five
      highly specific clinical risk criteria that may be useful in quickly identifying
      high-need injured persons presenting to non-tertiary hospitals. If validated,
      presence of these criteria may justify early higher level of care transfer by
      emergency medical services or mobilization of trauma resources without waiting
      for results of further diagnostic studies.

PMID- 17454802
TI  - Consecutive field trials using two different intraosseous devices.
AB  - OBJECTIVE: Establishing traditional intravenous (IV) access in adult trauma and
      medical patients can be difficult. We evaluated provider performance for
      obtaining intraosseous access with two FDA-approved intraosseous devices
      (F.A.S.T.1 and EZ-IO) in two sequential field trials. METHODS: One hundred twenty
      four providers consented to participate in the first field trial evaluating the
      use of the F.A.S.T.1 system. Three hundred eighty-nine providers consented to
      participate in the second field trial, evaluating the use of the EZ-IO. Following
      each insertion attempt, a telephone data collection process with a member of the
      research team was completed. Insertion success rate and measures of provider
      comfort and satisfaction with each device were collected and analyzed. RESULTS:
      One hundred seventy-eight insertions (89 F.A.S.T.1; 89 EZ-IO) were completed
      between February 2000 and December 2005. Sixty-four of the 89 insertions of the
      F.A.S.T.1 were successful, and 78 of the 89 insertions of the EZ-IO were
      successful (72% vs. 87%; chi2 = 6.8; p = 0.009). Providers using the F.A.S.T.1
      attempted more IV insertions prior to using the IO device than the providers
      using the EZ-IO (2.6 vs. 2.0, p = 0.005). There were no differences in provider
      comfort or provider assessed device performance between the two devices (p =
      0.52; p = 0.13, respectively). CONCLUSION: In our comparison of two field trials
      of prehospital provider use of the F.A.S.T.1 and EZ-IO systems, more successful
      insertions with the EZ-IO were achieved than with the F.A.S.T.1 device.
      Limitations of our comparison include nonrandomization, the sequential field
      trial design, the potential for a learning effect, and self-reporting of data
      points by providers. A prospective, randomized evaluation of these devices is
      warranted to draw definitive conclusions about provider insertion success rate
      with these devices.

PMID- 17454803
TI  - Chitosan dressing provides hemostasis in swine femoral arterial injury model.
AB  - OBJECTIVE: Chitosan dressings have been shown to be effective in improving
      survival of severe parenchymal injuries in an animal model and in treating
      prehospital combat casualties. Our goal was to test the efficacy of chitosan
      acetate dressings in providing durable hemostasis in a high-flow arterial wound
      model. METHODS: A proximal arterial injury was created with 2.7-mm vascular
      punches in both femoral arteries of fourteen anesthetized swine. By using a
      crossover design, 48-ply gauze (48PG) or a chitosan dressing (HC) was applied
      with pressure to the injury for 3 minutes and then released. If hemostasis was
      not maintained for 30 minutes, a second identical attempt was made by using the
      same dressing type. If hemostasis was still not achieved, the dressing was
      considered an acute failure and the alternate dressing type was applied. If
      failure of hemostasis occurred between 30 and 240 minutes after application, the
      dressing was considered a chronic failure and the artery was ligated. RESULTS:
      All 25/25 (100%) of the HC tests and 3/14 (21%) of the 48PG maintained hemostasis
      for 30 minutes. At 240 minutes, 21/25 (84%) of the HC tests and 1/14 (7%) of the
      48PG maintained hemostasis. Statistical analysis by Fischer's exact test shows a
      significant (p < 0.001) difference in hemostatic efficacy between the 48PG and HC
      groups in this model, both at 30 minutes and at 240 minutes. CONCLUSION: Chitosan
      acetate hemorrhage control dressings provided superior hemostasis to 48 ply gauze
      in high inguinal femoral arterial injuries. Chitosan-based dressings may provide
      prehospital treatment options for hemostasis in patients with severe hemorrhagic
      arterial injuries.

PMID- 17454804
TI  - Effects of an impedance threshold device on hemodynamics and restoration of
      spontaneous circulation in prolonged porcine ventricular fibrillation.
AB  - BACKGROUND: An impedance threshold device (ITD) has been designed to enhance
      circulation during CPR by creating a negative intrathoracic pressure during the
      relaxation phase of chest compression. HYPOTHESIS: We sought to determine the
      effects of the ITD on coronary perfusion pressure (CPP), return of spontaneous
      circulation (ROSC), and short-term survival (20 minutes after ROSC). We
      hypothesized that the ITD would improve all 3 variables when compared to standard
      CPR. METHODS: Using a case-control design nested within a randomized primary
      study, we compared CPR with the ITD (ITD-CPR) to standard CPR without the device
      (S-CPR). We systematically assigned 36 domestic swine, weighing 23-29 kg, (18 per
      group) to resuscitation with either ITD-CPR or S-CPR after 8 minutes of untreated
      ventricular fibrillation (VF). At minute 8, mechanical chest compression and
      ventilation began, and drugs (0.1 mg/kg epinephrine, 40U vasopressin, 1.0 mg
      propranolol, 1 mEq/kg sodium bicarbonate) were given. The first rescue shock
      (150J biphasic) was delivered at minute 11 of VF. We recorded CPP, ROSC (systolic
      pressure > 80 mmHg sustained for 60 s continuously), and survival. Data were
      analyzed with Fisher's exact test and generalized estimating equations (GEE),
      with alpha = 0.05. RESULTS: We analyzed 3,150 compressions. CPP for the ITD-CPR
      group (28.1 mmHg [95% CI 27-29.3 mmHg]), did not differ from the S-CPR group
      (32.3 mmHg [95% CI 31.2-33.4 mmHg]). ROSC occurred in 6/18 (33%) animals in the
      ITD-CPR, and 14/18 (78%) in the S-CPR group (p = 0.02). Survival occurred in 3/18
      (17%) ITD-CPR and 13/18 (72%) S-CPR group (p = 0.003). CONCLUSIONS: ITD-CPR did
      not improve CPP compared to S-CPR. ROSC and survival were significantly lower
      with ITD-CPR.

PMID- 17454805
TI  - Statewide survey of 911 communication centers on acute stroke and myocardial
      infarction.
AB  - OBJECTIVE: We conducted a statewide survey of communication centers regarding
      practices, training, and outreach for stroke and myocardial infarction (MI) and
      explored differences for those that were Emergency Medical Dispatch (EMD)
      certified or not. METHODS: A survey was mailed to all 115 centers that dispatched
      for emergency medical services (EMS) in North Carolina. Seventy-four percent
      (85/115) returned the survey. RESULTS: For 31% of centers, all telecommunicators
      were EMD-certified, 28% of centers had some personnel certified, and 41% had no
      personnel certified. Forty-four percent of centers used dispatch guides or
      algorithms to aid telecommunicators. If telecommunicators suspected a stroke, 47%
      of the centers provided prearrival instructions and if they suspected an MI, 49%
      provided prearrival instructions. In the past 2 years, 27% of the
      telecommunicators received stroke-specific training and 29% received MI-specific
      training. Stroke or MI training for telecommunicators was more common among the
      EMD centers (51% stroke; 51% MI) than among the non-EMD centers (5% stroke; 9%
      MI). Only one center conducted a community outreach program about stroke or MI in
      the last 6 months. CONCLUSIONS: Our results suggest that the development of
      statewide telecommunication training program to improve knowledge and care for
      suspected stroke or MI is needed in North Carolina. Dispatching for stroke and MI
      could be enhanced by requiring all communication centers to be EMD-certified and
      by creating consistent and standard dispatching practices across the state, using
      triage algorithms. Implementing these changes could improve rapid response and
      care for acute stroke and MI patients.

PMID- 17454806
TI  - The ability of emergency medical dispatch codes of medical complaints to predict
      ALS prehospital interventions.
AB  - OBJECTIVE: The Medical Priority Dispatch System (MPDS) is an emergency medical
      dispatch (EMD) system that is commonly used to triage 9-1-1 calls and optimize
      paramedic and EMT dispatch. The objective of this study was to determine the
      sensitivity, specificity, and positive and negative predictive values of selected
      MPDS dispatch codes to predict the need for ALS medication or procedures.
      METHODS: Patients with selected MPDS codes between November 1, 2003, and October
      31, 2005, from a suburban California county were matched with their electronic
      patient care record. The records of all transported patients were queried for
      prehospital interventions and matched to their MPDS classification [Basic Life
      Support (BLS) versus Advanced Life Support (ALS)]. Patients who received
      prehospital interventions or medications were considered ALS Intervention. With
      true positive = ALS by MPDS + ALS Intervention, true negative = BLS by MPDS + BLS
      Interventions, false positive = ALS by MPDS + BLS Interventions, and false
      negative = BLS by MPDS + ALS Interventions, the screening performance of the San
      Mateo County EMD system was determined for selected complaint categories
      (abdominal pain, breathing problems chest pain, sick person, seizures, and
      unconscious/fainting). RESULTS: There were a total of 64,647 medical calls, and
      42,651 went through the EMD process; 31,187 went through the EMD process and were
      transported; 22,243 of these were matched to a patient care record. The
      sensitivity and specificity with 95% confidence intervals in () were as follows:
      all EMD calls 84 (83-85), 36 (35-36); abdominal pain, 53 (41-65), 47 (43-51);
      chest pain 99 (99-100), 2 (1-3); seizure 83 (77-88), 20 (17-23), sick 59 (53-64),
      51 (49-54), and unconscious/fainting 99 (98-100), 2 (2-3). CONCLUSION: In our EMS
      system, MPDS coding for all medical calls had high sensitivity and low
      specificity for the prediction of calls that required ALS intervention. Chest
      pain and unconscious/fainting calls were screened with very high sensitivity but
      very low specificity.

PMID- 17454807
TI  - Are EMS call volume predictions based on demand pattern analysis accurate?
AB  - Most EMS systems determine the number of crews they will deploy in their
      communities and when those crews will be scheduled based on anticipated call
      volumes. Many systems use historical data to calculate their anticipated call
      volumes, a method of prediction known as demand pattern analysis. OBJECTIVE: To
      evaluate the accuracy of call volume predictions calculated using demand pattern
      analysis. METHODS: Seven EMS systems provided 73 consecutive weeks of hourly call
      volume data. The first 20 weeks of data were used to calculate three common
      demand pattern analysis constructs for call volume prediction: average peak
      demand (AP), smoothed average peak demand (SAP), and 90th percentile rank (90%R).
      The 21st week served as a buffer. Actual call volumes in the last 52 weeks were
      then compared to the predicted call volumes by using descriptive statistics.
      RESULTS: There were 61,152 hourly observations in the test period. All three
      constructs accurately predicted peaks and troughs in call volume but not exact
      call volume. Predictions were accurate (+/-1 call) 13% of the time using AP, 10%
      using SAP, and 19% using 90%R. Call volumes were overestimated 83% of the time
      using AP, 86% using SAP, and 74% using 90%R. When call volumes were
      overestimated, predictions exceeded actual call volume by a median (Interquartile
      range) of 4 (2-6) calls for AP, 4 (2-6) for SAP, and 3 (2-5) for 90%R. Call
      volumes were underestimated 4% of time using AP, 4% using SAP, and 7% using 90%R
      predictions. When call volumes were underestimated, call volumes exceeded
      predictions by a median (Interquartile range; maximum under estimation) of 1 (1
      2; 18) call for AP, 1 (1-2; 18) for SAP, and 2 (1-3; 20) for 90%R. Results did
      not vary between systems. CONCLUSION: Generally, demand pattern analysis
      estimated or overestimated call volume, making it a reasonable predictor for
      ambulance staffing patterns. However, it did underestimate call volume between 4%
      and 7% of the time. Communities need to determine if these rates of over-and
      underestimation are acceptable given their resources and local priorities.

PMID- 17454808
TI  - Central venous access by air medical personnel.
AB  - BACKGROUND: Vascular access is vital in the resuscitation of critically ill and
      injured patients for both fluid resuscitation and the delivery of medications.
      However, peripheral access is not always possible in patients with hypovolemia or
      difficult anatomy. Central venous access is an alternative vascular access
      strategy for air medical crews, offering the advantage of relatively predictable
      anatomy, even in unstable patients. The success and complication rates for the
      procedure in the hands of flight air medical personnel must be considered in the
      decision to institute a central venous access procedure. OBJECTIVE: To explore
      success and complication rates for central venous access attempts in patients
      treated by air medical crews. METHODS: This was a retrospective review using
      advanced procedure quality improvement forms. All air medical patients in whom an
      attempt at central venous access was made over a 30-month period were included.
      Femoral and subclavian lines were compared for incidence, success rates, and
      complications. RESULTS: A total of 50 patients were identified over the 30-month
      study period. The incidence of femoral and subclavian attempts was approximately
      equal. The overall success rate was 66% (60% for subclavian, 67% for femoral, and
      73% for nonspecified site). The mean number of attempts was 1.2 for each
      approach. The only reported complication was an arterial placement during a
      subclavian attempt. CONCLUSIONS: We observed moderate success rates and a low
      incidence of reported complications with air medical central venous access
      attempts.

PMID- 17454809
TI  - Incidence and significance of upper body cyanosis in nontraumatic cardiac arrest.
AB  - OBJECTIVE: Upper body cyanosis is a physical finding sometimes noted at the time
      of cardiac resuscitation. We attempted to determine the incidence and
      significance of upper body cyanosis in cases of nontraumatic cardiac arrest.
      METHODS: This was a retrospective case-control study. We reviewed all
      nontraumatic cardiac arrests evaluated by King County, Washington emergency
      medical system (EMS) personnel during 2000-2004 and identified patients with
      upper body or nipple-line cyanosis. Those patients who were autopsied comprised
      the cases for our study. Cases were age and sex matched with controls who also
      had cardiac arrest with an autopsy but no mention of cyanosis. RESULTS: EMS
      personnel treated 3,526 patients, age 18 and older, for nontraumatic out-of
      hospital cardiac arrest. One hundred eight (3.1%) had specific mention of upper
      chest or nipple-line cyanosis, of whom 38 had autopsy. Among the 38 autopsy
      cases, 6 were died of hemopericardium compared to none in age-and sex-matched
      controls. CONCLUSION: Cardiac arrest with upper chest or nipple-line cyanosis had
      a higher incidence of hemopericardium or dissecting thoracic aortic aneurysm than
      patients without mention of cyanosis.

PMID- 17454810
TI  - Evaluation of respiratory function during Reeves stretcher use.
AB  - OBJECTIVE: We were aware of a small number of cases in our EMS system where
      patients in respiratory distress had a worsening of their condition after being
      removed from the home on a Reeves stretcher (RS). We sought to determine if this
      prehospital lifting device causes additional respiratory effort used in normal
      subjects by describing changes in heart rate, pulse oximetry, tidal volume,
      minute ventilation, and respiratory rate. METHODS: Forty-nine subjects were
      entered into this study. Data were collected while the subject was supine on the
      floor in the RS and once while suspended over the floor in the device. A
      randomized crossover design was used. Ten subjects were excluded because of
      inadvertent omission of a nose plug during spirometry. Data points were recorded
      in the final minute of a 3-minute exposure. Three minutes was chosen to simulate
      a prehospital transport time from the scene to the ambulance. Minute ventilation,
      tidal volume, heart rate, pulse oximetry, and respiratory rate were recorded for
      each subject during each phase. Subjects were also asked to rate the difficulty
      of breathing using the modified Borg scale. RESULTS: Data were obtained for 39
      subjects. The mean respiratory rate while suspended was 9.9 +/- 3.0 breaths per
      minute compared to 9.1 +/- 2.5 breaths per minutes supine on the floor (p =
      0.007). The mean minute ventilation while suspended in a RS was 8.17 +/- 3.25
      L/min versus 7.37 +/- 2.37 while lying flat (p = 0.03). There was no difference
      in tidal volume, heart rate, pulse oximetry, or subjective modified Borg scale
      ratings. CONCLUSIONS: Subjects suspended in a RS for 3 minutes had statistically
      higher respiratory rates and minute ventilation than the same subjects lying
      flat. Although these modest changes are clinically insignificant in normal
      subjects, they could present a significant challenge to subjects in respiratory
      distress.

PMID- 17454811
TI  - Unrecognized misplacement of endotracheal tubes by ground prehospital providers.
AB  - OBJECTIVE: Endotracheal intubation by emergency medical services (EMS) is well
      established. Esophageal misplacement is a catastrophic complication that has
      until recently been studied by using methods that have called into question the
      accuracy of the reported data. The purpose of our study was to determine the
      incidence of unrecognized endotracheal tube misplacement, reasons for deferred
      intubations in the field, and to report outcomes in those patients with
      unrecognized misplacement. METHODS: This was a prospective observational study
      with a consecutive sample. All arriving with an endotracheal tube or in whom
      endotracheal intubation was performed within 10 minutes of arrival were included,
      and a physician immediately determined placement. Hospital records were reviewed
      to determine outcome of those patients in whom the tube was misplaced.
      Unrecognized esophageal misplacement triggered communication to the medical
      director of the transporting agency. RESULTS: During the enrollment period, 192
      patients were evaluated. Overall, 132 of 192 (69%) were intubated in the
      prehospital environment, and 60 were intubated within 10 minutes of arrival in
      the emergency department. Among prehospital intubation attempts, 12 of 132 (9%;
      95 CI 5.3-15.2), 11 esophageal, and 1 hypopharyngeal were misplaced. Right
      mainstem intubation occurred in an additional 20 of 132 (15%; 95 CI 10.0-22.3).
      Among patients arriving with unrecognized esophageal misplacement of the
      endotracheal tube, one patient survived to hospital discharge. CONCLUSION: The
      rate of esophageal misplacement of endotracheal tubes in the prehospital
      environment in our urban setting and the poor clinical course of patients with
      unrecognized misplacement is consistent with previous reports, suggesting that
      the benefit of prehospital airway management does not clearly supercede the
      potential risks.

PMID- 17454812
TI  - Paramedic perceptions of challenges in out-of-hospital endotracheal intubation.
AB  - OBJECTIVE: Paramedics often perform endotracheal intubation (ETI), insertion of a
      breathing tube, on critically ill out-of-hospital patients. Recent studies
      highlight important paramedic ETI shortcomings including adverse events, errors,
      and poor outcomes resulting from this procedure. Little is known about workforce
      perceptions of these events. We sought to identify paramedic and physician
      perceptions regarding the challenges and pitfalls of out-of-hospital ETI.
      METHODS: We conducted a qualitative study involving paramedic focus groups
      sessions and individual interviews with Emergency Medical Services (EMS)
      physician medical directors. We recorded and transcribed all sessions. We used
      inductive theory construction to examine, organize, and classify thematic
      patterns. RESULTS: Fourteen paramedics and 6 physicians participated. Although
      paramedics and physicians recognized problems with paramedic ETI, all
      participants strongly felt that paramedics should continue to perform the
      procedure. Physicians and paramedics disagreed about the ability of paramedics to
      perform neuromuscular blockade-assisted intubation. Both groups identified
      aspects of paramedic education, skills acquisition, and maintenance as core
      issues. Participants also identified broader factors about the structure of
      emergency services, the role of the medical director, and workforce culture and
      professionalism. CONCLUSION: Paramedics and EMS physicians attribute paramedic
      ETI performance to a myriad of factors involving EMS education, organization,
      oversight, retention, and professionalism. Efforts to improve ETI must include
      strategies to address multiple aspects of EMS operations and culture.

PMID- 17454813
TI  - Endotracheal intubation increases out-of-hospital time in trauma patients.
AB  - OBJECTIVES: Prior efforts have linked field endotracheal intubation (ETI) with
      increased out of hospital (OOH) time, but it is not clear if the additional time
      delay is due to the procedure, patient acuity, or transport distance. We sought
      to assess the difference in OOH time among trauma patients with and without OOH
      ETI after accounting for distance and other clinical variables. METHODS:
      Retrospective cohort analysis of trauma patients 14 years or older transported by
      ground or air to one of two Level 1 trauma centers from January 2000 to December
      2003. Geographical data were probabilistically linked to trauma registry records
      for transport distance. Trauma registry OOH time (interval from 9-1-1 call to
      hospital arrival) was validated against a subset of linked ambulance records
      using Bland-Altman plots and tested by using the Spearman rank correlation
      coefficient. Based on the validation, the sample was restricted to patients with
      OOH time 100 minutes or less. The propensity for OOH-ETI was calculated by using
      field vital signs, demographics, mechanism, transport mode, comorbidities,
      Abbreviated Injury Scale head injury 3 or greater, injury severity score, blood
      transfusion, and major surgery. Multivariable linear regression (outcome = total
      OOH time) was used to assess the time increase (minutes) associated with OOH-ETI
      after adjusting for distance, propensity for OOH-ETI, and mode of transport.
      RESULTS: A total of 8,707 patients were included in the analysis, of which 570
      (6.5%) were intubated in the field. Adjusted only for distance, OOH times
      averaged 6.1 minutes longer (95% CI 4.2-7.9) among patients intubated with RSI.
      After including other covariates, OOH time was 10.7 minutes (95% CI 7.7-13.8)
      longer among patients with RSI and 5.2 minutes (95% CI 2.2-8.1) longer among
      patients with conventional ETI. The time difference was greatest farther from the
      hospital. CONCLUSIONS: Patients with OOH-ETI have increased total OOH time,
      especially among those using RSI, even after accounting for distance and other
      clinical factors. Injured patients may benefit from airway management techniques
      that require less time for execution.

PMID- 17454814
TI  - Strategies to improve sleep during extended search and rescue operations.
AB  - OBJECTIVE: This study investigated strategies to improve sleeping conditions
      during search and rescue operations during disaster response. METHODS: Forty
      members of the Montgomery County (Maryland) Urban Search and Rescue Team were
      surveyed for individual sleep habits and sleeping aids used during extended
      deployments. Team members were also asked to suggest methods to improve sleep on
      future deployments. RESULTS: The average amount of sleep during field operations
      was 5.4 hours with a range of 4-8 hours. Eight percent surveyed would prefer
      another schedule besides the 12-hour work day, all of whom proposed three 8-hour
      shifts. Fifteen percent of participants were interested in a pharmacological
      sleeping aid. Fifty percent of search and rescue members interviewed would
      consider using nonpharmacological sleeping aids. Furthermore, 40% of participants
      stated they had successfully devised self-employed methods of sleep aids for
      previous deployments, such as ear plugs, massage, mental imagery, personal
      routines, music and headphones, reading, and blindfolds. CONCLUSIONS: This study
      suggests that availability of both pharmacological and nonpharmacological
      sleeping aids to search and rescue workers via the team cache could impact the
      quantity of sleep. Further investigation into methods of optimizing sleep during
      field missions could theoretically show enhanced performance through various
      aspects of missions including mitigation of errors, improved productivity, and
      improved overall physiological and emotional well-being of search and rescue
      personnel.

PMID- 17454815
TI  - Cognitive control and prehospital endotracheal intubation.
AB  - Prehospital endotracheal intubation (ETI) is a commonly performed but complex
      procedure. Cognitive psychology is a science describing how humans organize and
      process thoughts, including those used in complex operations. We use Rasmussen's
      Skills-Rules-Knowledge (SRK) framework to highlight the cognitive complexities of
      prehospital ETI. These findings have important implications for prehospital
      education and care.

PMID- 17454817
TI  - Can methicillin-resistant Staphylococcus aureus be found in an ambulance fleet?
AB  - OBJECTIVE: To perform an initial screening study of methicillin-resistant
      Staphylococcus aureus (MRSA) contamination in an ambulance fleet. METHODS: This
      was a cross-sectional study of MRSA contamination in an ambulance fleet operating
      in the western United States in June 2006. Five specific areas within each of 21
      ambulances (n = 105) were tested for MRSA contamination using dacron swabs
      moistened with a 0.85% sterile saline solution. These samples were then plated
      onto a screening media of mannitol salt agar containing 6.5% NaCl and 4 mcg/mL
      oxacillin. RESULTS: Thirteen samples isolated from 10 of the 21 ambulances
      (47.6%) in the sample group tested positive for MRSA. CONCLUSIONS: The results of
      this preliminary study suggest that ambulances operating in the emergency medical
      services (EMS) system may have a significant degree of MRSA contamination and may
      represent an important reservoir in the transmission of potentially serious
      infections to patients.

PMID- 17454818
TI  - Feasibility of laryngeal mask airway use by prehospital personnel in simulated
      pediatric respiratory arrest.
AB  - INTRODUCTION: Pediatric respiratory arrest is a technically challenging scenario
      infrequently faced by prehospital providers. Prehospital endotracheal intubation
      (ETI) is a complex procedure, and one study showed that it may result in worse
      neurological outcome in these patients. Alternatives to ETI include bag-valve
      mask (BVM) ventilation and the laryngeal mask airway (LMA). Although the LMA has
      been used successfully for pediatric resuscitation in the hospital setting, there
      is no data describing its use in the prehospital setting. HYPOTHESIS: Prehospital
      providers can successfully place and ventilate the pediatric LMA in a simulated
      pediatric respiratory arrest. METHODS: Paramedic students received a 1-hour
      training session covering the use of the pediatric LMA. Subjects performed airway
      management of a simulator manikin using both the LMA and the BVM. Rate of
      successful LMA placement, time to first ventilation, tidal volume by weight, and
      ventilations per minute were recorded. A generalized estimating equation analysis
      was completed to determine the effects of time and ventilation technique.
      RESULTS: All 13 subjects (100%) successfully ventilated the mannequin with both
      techniques. The median number of attempts required to successfully place the LMA
      was one. Median time from the start of the scenario to BVM ventilation was 4
      seconds (IQR 3, 5), and the median for LMA ventilation was 30 seconds (IQR 25,
      52). Tidal volumes were significantly greater with BVM ventilation (5.07 mL/kg
      [IQR 4.47, 5.43]) than with LMA ventilation (2.88 mL/kg [IQR 2.17, 4.04]). An
      obvious air leak was present in all LMA cases, potentially resulting in reduced
      tidal volume delivery. Excessive ventilatory rates were noted in both BVM (42
      ventilations per minute [IQR 33, 46]) and LMA (37 ventilations per minute [IQR
      31, 39]) groups. CONCLUSIONS: Prehospital providers were able to place and
      ventilate a simulated pediatric respiratory arrest patient using the LMA after a
      brief educational intervention. Obvious air leakage was noted when ventilating
      with the LMA and likely represents one technical limitation of using a simulator.

PMID- 17454819
TI  - Rapid Sequence Airway (RSA)--a novel approach to prehospital airway management.
AB  - This article presents a case in which an air medical flight crew encountered a
      potentially difficult airway when a trauma patient deteriorated in-flight. The
      crew elected to sedate and paralyze the patient and place a laryngeal mask airway
      without a prior attempt at direct laryngoscopy and endotracheal intubation. The
      term Rapid Sequence Airway (RSA) is coined for this novel approach. This article
      describes and supports this concept and provides definitions of alternative and
      failed airways.

PMID- 17454820
TI  - Ultrasound enhances retrovirus-mediated gene transfer.
AB  - Viral vector systems are efficient for transfection of foreign genes into many
      tissues. Especially, retrovirus based vectors integrate the transgene into the
      genome of the target cells, which can sustain long term expression. However, it
      has been demonstrated that the transduction efficiency using retrovirus is
      relatively lower than those of other viruses. Ultrasound was recently reported to
      increase gene expression using plasmid DNA, with or without, a delivery vehicle.
      However, there are no reports, which show an ultrasound effect to retrovirus
      mediated gene transfer efficiency. Retrovirus-mediated gene transfer systems were
      used for transfection of 293T cells, bovine aortic endothelial cells (BAECs), rat
      aortic smooth muscle cells (RASMCs), and rat skeletal muscle myoblasts (L6 cells)
      with beta-galactosidase (beta-Gal) genes. Transduction efficiency and cell
      viability assay were performed on 293T cells that were exposed to varying
      durations (5 to 30 seconds) and power levels (1.0 watts/cm(2) to 4.0 watts/cm(2))
      of ultrasound after being transduced by a retrovirus. Effects of ultrasound to
      the retrovirus itself was evaluated by transduction efficiency of 293T cells.
      After exposure to varying power levels of ultrasound to a retrovirus for 5
      seconds, 293T cells were transduced by a retrovirus, and transduction efficiency
      was evaluated. Below 1.0 watts/cm(2) and 5 seconds exposure, ultrasound showed
      increased transduction efficiency and no cytotoxicity to 293T cells transduced by
      a retrovirus. Also, ultrasound showed no toxicity to the virus itself at the same
      condition. Exposure of 5 seconds at the power of 1.0 watts/cm(2) of an ultrasound
      resulted in significant increases in retrovirus-mediated gene expression in all
      four cell types tested in this experiment. Transduction efficiencies by
      ultrasound were enhanced 6.6-fold, 4.8-fold, 2.3-fold, and 3.2-fold in 293T
      cells, BAECs, RASMCs, and L6 cells, respectively. Furthermore, beta-Gal
      activities were also increased by the retrovirus with ultrasound exposure in
      these cells. Adjunctive ultrasound exposure was associated with enhanced
      retrovirus-mediated transgene expression in vitro. Ultrasound associated local
      gene therapy has potential for not only plasmid-DNA-, but also retrovirus
      mediated gene transfer.

PMID- 17454821
TI  - Purification and some properties of thiosulfate dehydrogenase from
      Acidithiobacillus ferrooxidans.
AB  - Thiosulfate dehydrogenase was purified from Acidithiobacillus ferrooxidans using
      three purification steps. The purification procedure involved ammonium sulfate
      fractionation, ion-exchange chromatography, and gel permeation chromatography.
      Specific activity of the purified enzyme (after IEC) was 3.26 nkat/mg, and yield
      of the enzyme was 78%. The purity of the enzyme was checked by polyacrylamide gel
      electrophoresis in the presence of sodium dodecyl sulfate. The enzyme is a
      tetramer composed of four probably identical subunits of relative molecular
      weight 45,000. The pH optimum of the enzyme reaction in the direction of
      substrate oxidation was found to be 3.0. The isoelectric point of the enzyme was
      8.3. Enzyme activity was found to be particularly sensitive to the histidine
      selective reagent diethylpyrocarbonate. Reagents selective for arginine,
      cysteine, and tryptophane had no effect on enzyme activity.

PMID- 17454822
TI  - Production of Gluconobacter oxydans cells from low-cost culture medium for
      conversion of glycerol to dihydroxyacetone.
AB  - Gluconobacter oxydans could be immobilized as a biocatalyst for the conversion of
      glycerol to dihydroxyacetone. To reduce the production cost, the cells were
      produced from agricultural byproducts. Corn meal hydrolysate and corn steep
      liquor were employed to replace of sorbitol and yeast extract as medium for G.
      oxydans cell production. The optimal medium contained 80 g/L reducing sugar, 25
      g/L corn steep liquor, and 10 g/L glycerol. The cell mass was about 4.22 g/L and
      the glycerol dehydrogenase activity was about 5.23 U/mL. For comparison, the cell
      mass was about 4.0 g/L and the glycerol dehydrogenase activity was about 5.35
      U/mL cultured in sorbitol and yeast extract medium. These studies shown the corn
      meal hydrolysate and corn steep liquor medium was similar in performance to a
      nutrient-rich medium, but the cost of production was only 15% of that cultured in
      sorbitol and yeast extract medium. It was an economical process for the
      production of G. oxydans cells as biocatalyst for the conversion of glycerol to
      dihydroxyacetone in industry.

PMID- 17454823
TI  - Identification and release kinetics of peptides from the process of peptic
      hydrolysis of bovine hemoglobin by LC-ESI-MS/MS.
AB  - Bovine hemoglobin was hydrolyzed with pepsin in a batch stirred tank reactor; the
      resulting peptides were identified, in a time dependent and comprehensive manner,
      using reversed phase-high performance liquid chromatography (RP-HPLC) coupled
      with electrospray ionization tandem mass spectrometry (ESI-MS/MS) by means of
      database searching. Peptic digestion of bovine hemoglobin yields more hydrophobic
      peptides at a low degree of hydrolysis, and more hydrophilic peptides at a later
      stage of hydrolysis. The release kinetics of the bioactive peptides was also
      followed based on the RP-HPLC profiles. In addition, the behavior of peptic
      digestion of hemoglobin alpha and beta chains was compared in terms of profiling
      the identified peptides. Thirty-two peptides were recovered by a process of
      hydrolysis from the alpha chain of the peptide; whereas the corresponding result
      for the beta chain was 19 peptides with around 67% sequence coverage. The main
      factor responsible for non-peptic susceptibility of the central region of the
      beta chain was their relatively higher hydrophilicity.

PMID- 17454824
TI  - Interaction of the protein C activation peptide with platelets.
AB  - The peptide NH(2)-DTEDQEDQVDPR-COOH is released during activation of protein C
      zymogen. We measured the effect of a synthetic peptide with an amino acid
      sequence similar to that of the natural peptide on platelets from healthy
      individuals using platelet aggregometry. We found that this synthetic peptide
      inhibits platelet aggregation induced by thrombin; furthermore, it diminishes
      mobilization of intraplatelet calcium. Molecular docking showed weak interaction
      between the synthetic peptide and thrombin. Our findings suggest that this
      synthetic peptide may interact with a receptor located on the platelet cell
      membrane.

PMID- 17454825
TI  - Separation and preparative purification of arachidonic acid from microbial lipids
      by urea inclusion reaction and HPLC.
AB  - Arachidonic acid (AA) was separated and purified from microbial lipids by the
      combined method of urea inclusion reaction and reversed-phase high performance
      liquid chromatography. At first, AA was concentrated from free fatty acids made
      from microbial lipids by a urea inclusion reaction. The optimum conditions were
      as follows: methanol was the suitable solvent, the ratio of free fatty acids to
      urea to methanol was 1:2:8 (wt/wt), and the temperature of the urea inclusion
      reaction was -10 degrees C. The AA content was increased from 38% to 79%, and
      then AA was purified on a C(18) preparative column (300 mm x 30 mm I.D., d(p)=15
      microm), using methanol-water (95:5, v/v) as the mobile phase, at a flow rate of
      5 mL/min. The purity of AA after two steps purification reached 99%. This result
      indicates that the combined method of the urea inclusion reaction and reversed
      phase high performance liquid chromatography is a promising technique for
      purification of AA.

PMID- 17454826
TI  - Microbiaeratin, a new natural indole alkaloid from a Microbispora aerata strain,
      isolated from Livingston Island, Antarctica.
AB  - A new sulphur-containing natural alkaloid named microbiaeratin (1a) was isolated,
      together with the known microbiaeratinin (2, bacillamide) from the culture
      filtrate of Microbispora aerata strain IMBAS-11A. The organism was isolated from
      penguin excrements collected on the Antarctic Livingston Island. The structure
      was elucidated by one- and two-dimensional NMR experiments and mass spectrometric
      investigations.

PMID- 17454829
TI  - Carotid endarterectomy should be performed within hours after a transient
      ischemic attack (TIA).

PMID- 17454830
TI  - Prevention of atrial fibrillation after cardiac surgery.
AB  - Atrial fibrillation is the most common arrhythmia occurring after heart surgery.
      Its prevalence after coronary artery bypass surgery is 17-33%. Atrial
      fibrillation requires additional treatment, lengthens hospitalization and
      increases the overall expenses of cardiac surgery. Atrial fibrillation can cause
      hemodynamic problems, predispose to congestive heart failure and increase the
      risk of stroke. Beta-blockers have been shown to effectively prevent atrial
      fibrillation, and beta-blockers should be a part of the medication of every
      patient undergoing cardiac surgery, if there are no contraindications. Amiodarone
      therapy can also be considered for especially high-risk patients.

PMID- 17454831
TI  - ECG changes in patients with acute ethanol intoxication.
AB  - OBJECTIVES: To assess how ethanol in potential lethal serum concentrations
      affects features of the ECG that may be associated with cardiac arrhythmias.
      DESIGN: We included 84 patients, who were hospitalised with assumed acute ethanol
      intoxication. In the emergency room resting ECG was recorded and blood was
      collected for serum osmolality measurement used as a proxy for ethanol level.
      Thirty-two also had ECG recorded at discharge. Twenty-seven hospitalised patients
      without known alcohol ingestion served as controls. ECG segment durations were
      compared with controls and related to intoxication level. RESULTS: In subjects
      with moderately elevated to high serum osmolality, the P wave and QTc intervals
      were prolonged compared with sober subjects. P wave, PR, QRS and QTc intervals
      were longer when the subjects had high blood ethanol levels (at admission) than
      at discharge (p-values: 0.0001, 0.0002, 0.010 and <0.0001 for P wave, PR, QRS and
      QTc intervals. n=32). CONCLUSIONS: Ethanol at high to very high blood
      concentration causes several changes in the ECG that might be associated with
      increased risk of arrhythmias.

PMID- 17454832
TI  - Changes in glycaemic control are related to the systolic function in type 1
      diabetes mellitus.
AB  - AIM: To examine whether changes in glycaemic control are related to the left
      ventricular function, in a group of type 1 diabetic patients. METHODS: We
      included 19 consecutive type 1 diabetic patients selected for insulin pump
      therapy due to poor metabolic control. The outcome measures were HbA1c and
      systolic left ventricular strain rate as measured by Tissue Doppler
      echocardiography. Mean follow-up period was 45 days (range 35-50). All patients
      included had an ejection fraction>55%. None had cardiac symptoms. RESULTS: The
      mean age of the participants was 40 years (range 22-65). Following initiation of
      insulin-pump therapy, the mean HbA1c improved significantly from 8.6+/-1.4% to
      7.6+/-1.1% (p<0.01). The mean strain rate of 16 myocardial segments also improved
      significantly, from -1.58+/-0.30 s-1 to -1.80+/-0.4 s-1 (p<0.01). In addition,
      there was a significant correlation between the changes in left ventricular
      function and the changes in HbA1c (delta-Strain rate vs. delta-HbA1c: r=0.49,
      p<0.01). CONCLUSION: Changes in glycaemic control resulting from insulin pump
      therapy seem significantly related to the systolic function of the left
      ventricle.

PMID- 17454833
TI  - Bradykinin induced sustained anti-adrenergic actions in guinea pig heart muscle
      involves PKC.
AB  - OBJECTIVES: Adenosine attenuates the effect of beta-adrenergic stimulation upon
      contractile force, both when present during beta-adrenergic stimulation and for a
      period after washout of adenosine. Protein kinase C (PKC) mediates the sustained
      effect. The present study investigated if bradykinin (500 nM) could induce anti
      beta-adrenergic actions. DESIGN: Guinea pig papillary muscles (36.5 degrees C, 1
      Hz) were subjected to 15 min exposure to and 20 min washout of bradykinin.
      Isoproterenol 100 nM was added for 3 min at the end of test exposure and at the
      end of washout. The PKC-inhibitor bisindolylmaleimide (20 nM) was given to
      investigate the importance of PKC. RESULTS: Bradykinin significantly reduced the
      increase in contractile force in response to isoproterenol, both when present and
      after washout of test substance. Inhibition of PKC abolished the sustained
      effect, while inhibition of PI3-kinase with wortmannin did not seem to affect the
      results. CONCLUSIONS: Anti-beta-adrenergic effects of bradykinin on contractile
      force and action potential duration were demonstrated. PKC was important for the
      sustained effect on contractile force, but not for the acute effect and the
      effect on action potential duration.

PMID- 17454834
TI  - Synergistically therapeutic effects of VEGF165 and angiopoietin-1 on ischemic rat
      myocardium.
AB  - PURPOSE: The aim of this study was to determine whether the combination of 2
      angiogenic growth factor, vascular endothelial growth factor 165(VEGF165) and
      angiopoietin-1 (Ang1), could increase angiogenesis and cardiomyocyte(CM)
      proliferation in an infarcted myocardium. METHODS: Myocardial ischemia was
      induced in rats by ligation of the left anterior descending (LAD) coronary
      artery. Replication-deficient adenoviruses encoding VEGF165 (Ad-VEGF165), Ang1
      (Ad-Ang1) or enhanced green fluorescence protein (Ad-EGFP) was injected into the
      ischemic myocardium immediately. Bromodexyuridine (BrdU) was administered
      intraperitoneally 1 week after ligation. One week later, the hearts were
      harvested and sectioned for hematoxylin-eosin (HE) and immunohistochemistry to
      evaluate densities of capillary, arteriole and double labelled BrdU(+) CM. M-mode
      echocardiography was used to evaluate the cardiac function. RESULTS: Ang1
      significantly increased collateral vessel formation. Both VEGF165 and Ang1
      significantly increased densities of capillary and arteriole, as well as the
      number of double labelled BrdU(+) CM, and improved cardiac function. CONCLUSION:
      Our results suggest that the combination of VEGF165 and Ang1 can increase both
      myocardial angiogenesis and CM proliferation following myocardial ischemia in
      rats, leading to improved cardiac function.

PMID- 17454835
TI  - Insulin resistance after cardiopulmonary bypass in the elderly patient.
AB  - OBJECTIVES: Preoperative carbohydrate administration attenuates insulin
      resistance. We studied effects of preoperative oral carbohydrate loading in
      elderly patients undergoing coronary artery bypass grafting. DESIGN: Eighteen
      patients were assigned either to get a carbohydrate drink or to be controls.
      Perioperatively, glucose was administered. A gastric emptying test was performed.
      Glucose and insulin concentrations were measured. Levels of glucose, insulin and
      stress hormones were studied pre-, per- and postoperatively. RESULTS AND
      DISCUSSION: Preoperative carbohydrate loading did not affect stress hormones.
      Gastric residual after the carbohydrate drink was 11+/-3% (mean+/-SEM). Glucose
      concentration was lower before anaesthesia induction in the carbohydrate group,
      possibly due to increased insulin release. Insulin levels differed at baseline,
      induction and day six. All patients returned to baseline on day six. CONCLUSIONS:
      The study group was insulin resistant on postoperative day one and two. The
      effects were explainable by the traumatic stress response. No adverse effect was
      noted from the carbohydrate drink. If glucose is administered intravenously
      during surgery, there is no obvious advantage of preoperative carbohydrate
      loading on insulin resistance or stress hormone response.

PMID- 17454836
TI  - Protein S100B after cardiac surgery: an indicator of long-term anxiety?
AB  - OBJECTIVES: The aim of the study was to assess long-term state and trait anxiety
      in cardiac surgical risk patients. DESIGN: Thirty two patients with serum
      S100B>0.3 microg/l 48 hours after cardiac surgery with cardiopulmonary bypass
      were matched according to age, gender, type, date and length of surgery with 35
      operated patients without elevated S100B. They completed Spielberger's Anxiety
      Inventory (STAI). RESULTS: Patients with elevated S100B reported more state
      anxiety and trait anxiety. S100B was an independent predictor of both state and
      trait anxiety when controlling for perioperative variables. CONCLUSIONS: Patients
      with elevated S100B reported more anxiety 3-6 years after cardiac surgery. A
      postoperative blood sample can identify risk patients and facilitate appropriate
      follow-up.

PMID- 17454837
TI  - Analysis of the myocardial metabolism by microdialysis during open beating heart
      surgery.
AB  - OBJECTIVES: Microdialysis allows the in vivo biochemical analysis of interstitial
      fluids. Our aim was to reveal in vivo reliable data of the myocardium during open
      beating heart surgery. DESIGN: In ten patients undergoing routine beating
      coronary artery bypass grafting a microdialysis catheter was inserted into the
      left ventricle. Measurements were performed up to 45 min after anastomosis. Data
      were retrospectively compared with standard on-pump procedures. RESULTS: The
      myocardial lactate remained stable during anastomosis, followed by a significant
      decrease of lactate after revascularisation. Myocardial glucose levels showed a
      slight decrease, followed by a significant increase after revascularisation.
      Myocardial purines showed a slight increase during anastomosis, followed by a
      sharp decrease during reperfusion period. CONCLUSIONS: In contrast to on-pump
      procedures myocardial lactate and purines showed less increasing trend during the
      ischemic period, while myocardial glucose remained stable as a sign of preserved
      tissue blood flow. Myocardial microdialysis showed different values compared to
      the elective on-pump CABG and previous animal studies. This technique allows
      bedside monitoring of biochemical changes, suggesting its possible role as a
      clinical monitoring tool.

PMID- 17454838
TI  - Aortic plaque distribution in relation to cross clamp and cannulation procedures
      during cardiac surgery.
AB  - OBJECTIVE: Aortic atherosclerosis may cause cerebrovascular accidents in cardiac
      surgery. Aortic plaque distribution was analyzed in relation to surgical
      manipulation. DESIGN: In 24 autopsy subjects the thoracic aorta was digitally
      analyzed by macro-anatomic mapping of plaques. Plaque density was compared in
      different anatomical segments. Hazards associated with surgical manipulation were
      blindly studied by superimposing cannulation and cross-clamp locations onto the
      maps. RESULTS: Plaques were frequent. The anterior wall of the ascending/arch
      aorta had higher plaque density than its posterior side (p=0.039). However, an
      anterior plaque predicted to 83% a concomitant plaque in the posterior wall.
      Plaque formation correlated with age (p=0.004). The theoretical risk of
      interfering with a plaque during cannulation and/or clamp positioning was 46%.
      CONCLUSIONS: Plaque formation is a frequent and age-dependent problem. In the
      surgery-exposed aorta, the anterior wall had higher plaque density than the
      posterior side, although the two sides showed strong plaque coexistence.
      Furthermore, there was an unexpectedly high risk of plaque interference during
      cannulation and/or clamp maneuvers if blindly performed. The present results
      emphasize the importance of epiaortic scanning.

PMID- 17454840
TI  - Decreased cerebrospinal fluid cytochrome c levels in patients with amyotrophic
      lateral sclerosis.
AB  - OBJECTIVE: There is evidence showing impaired mitochondrial energy production and
      increased oxidative damage to mitochondria in amyotrophic lateral sclerosis
      (ALS). It is known that a lack of cytochrome c (CyC) in the mitochondrial
      intermembrane space can increase free radical release from mitochondria through
      interruption of the electron transport. CyC also plays a role in the apoptotic
      cell death which is suspected in ALS. The aim of the study was to measure
      cerebrospinal fluid (CSF) and serum CyC levels in patients with ALS. MATERIAL AND
      METHODS: Forty ALS patients were diagnosed according to the El Escorial criteria
      of ALS. The clinical state of the patients was measured using the Amyotrophic
      Lateral Sclerosis Functional Rating Scale [ALSFRS]. RESULTS: It was shown that
      overall CyC levels were significantly decreased by 46 % in the CSF of patients
      with ALS compared with controls (p<0.05), and not affected in serum of patients
      with ALS (p>0.05). There was no significant difference in CyC levels in relation
      to the clinical parameters of the disease (p>0.05). CONCLUSIONS: The study
      indicates that CyC may play a role in the pathogenesis of ALS. A possible
      mechanism is that increased neurodegeneration in ALS caused by free radical
      production decreases the concentrations of CyC.

PMID- 17454839
TI  - High C-reactive protein levels are associated with oral hormonal menopausal
      therapy but not with intrauterine levonorgestrel and transdermal estradiol.
AB  - OBJECTIVE: Oral hormone replacement therapy (HRT) has been linked to increased
      cardiovascular (CVD) morbidity. HRT causes a sustained increase in C-reactive
      protein (CRP), an excellent marker of subclinical inflammation and CVD. The aim
      of the study was to support our hypothesis that CRP, which is synthesized in the
      liver, is not increased in association with transdermal/intrauterine HRT.
      MATERIAL AND METHODS: A case-control study was performed in which CRP
      measurements in women receiving levonorgestrel intrauterine system combined with
      transdermal estradiol (LNG/TDE, n=27) were followed for 9 months or longer. CRP
      concentrations in these women were compared with those of either oral HRT users
      (n=20) or controls (n=19). RESULTS: No significant differences were found in CRP
      concentrations between the LGN/TDE and control groups (1.8+/-1.2 and 1.8+/-1.8
      mg/L, respectively). However, CRP was significantly increased in the oral HRT
      group (5.5+/-2.9 mg/L, p<0.001). CONCLUSIONS: CRP is significantly increased by
      oral HRT but not by the LNG/TDE combination after 9 months of treatment. This
      trend may explain the preponderance of some menopausal women on HRT being at
      increased risk for the development of CVD. Therefore, the use of LNG/TDE is
      acceptable for relief of severe climacteric symptoms possibly not imposing an
      increased CVD risk documented upon oral HRT.

PMID- 17454841
TI  - Lupus anticoagulant is significantly associated with inflammatory reactions in
      patients with suspected deep vein thrombosis.
AB  - OBJECTIVE: Lupus anticoagulant (LA) and antiphospholipid antibodies (aPL) are
      suggested as risk factors for development of deep vein thrombosis (DVT) among
      patients without systemic lupus erythematosus (SLE). Other conditions, e.g.
      inflammation, are reported to induce LA and it is uncertain whether the
      association between LA and DVT is causal. In this study the associations between
      aPL, LA and inflammation were investigated in 170 consecutive patients without
      SLE, but with a tentative diagnosis of DVT. MATERIAL AND METHODS: DVT was
      diagnosed in 64 patients. LA was determined according to the criteria of the
      International Society of Thrombosis and Haemostasis. The concentration of
      anticardiolipin (aCL) and beta(2)-glycoprotein I (anti-beta(2)-GPI) antibodies as
      well as C-reactive protein (CRP) was determined with sensitive and precise
      methods. RESULTS: LA was demonstrated in 8 patients with DVT and in 10 patients
      without DVT, relative risk 1.33 (CI: 0.55-3.18). No significant association was
      observed between aCL or anti-beta(2)-GPI and DVT. Patients suffering from DVT had
      significantly higher concentrations of CRP than patients without DVT. However,
      CRP was also significantly higher in patients positive for LA than in patients
      without LA irrespective of the presence of DVT (p<0.001). CONCLUSIONS: The
      present study supports a strong association between inflammatory reactions and
      development of LA in patients with suspected DVT, whereas no significant
      association was demonstrated between LA or aPL and DVT.

PMID- 17454842
TI  - Genotyping of the cytochrome P450 2D6 4469 C>T polymorphism using SimpleProbes.
AB  - BACKGROUND: Genotyping of human cytochrome P450s is a pharmacogenetic approach to
      diagnosing inherited deficiencies in drug metabolizing enzymes that influence
      therapeutic responses. The P450 CYP2D6 (debrisoquine hydroxylase) metabolizes
      numerous antidepressants and neuroleptic agents and there is evidence of a
      relationship between gene polymorphism and variant therapeutic response.
      Polymorphism in CYP2D6 causes poor, intermediate, efficient or ultrarapid
      metabolization of substrate drugs affecting pharmacokinetic parameters and
      requiring dose adjustments. Predictive genotyping for broader clinical
      application is reliant on fast, technically simple analyses. A new genotyping
      method was explored. It identifies the single nucleotide polymorphism (SNP) 4469
      C>T (NCBI access no. M33388) with one fluorescent hybridization probe
      (SimpleProbes; SP) using the LightCycler (LC). This SNP is found in 21 alleles,
      comprising 30% in Caucasian populations and encoding enzymes with poor,
      intermediate or efficient activity. The remaining 65 known alleles either harbour
      a C in position 4469 or are deletion mutants. METHODS: Comparative detection of
      C>T polymorphism was done using a well-established polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) technique and PCR followed by
      melting-point (T(m)) analysis with an SP covering the SNP position in 144 samples
      encompassing alleles *2 and *41 with a T, alleles *1,*3, *4, *6, *9, *10, *15
      with a C and the deletion mutant allele *5. RESULTS: C>T polymorphism was
      detected with complete concordance. T(m) of SP/target heteroduplex complexes for
      C was: T(m) 67, 89 degrees C to 68, 62 degrees C and for T: T(m) 60, 70 degrees C
      to 61, 51 degrees C. CONCLUSION: By one-step SP methodology it proved possible
      within 2 h to identify an SNP in genotypes comprising >90% in Caucasian
      populations.

PMID- 17454843
TI  - Changes in leptin serum levels in HIV-infected children receiving highly active
      antiretroviral therapy.
AB  - Highly active antiretroviral therapy (HAART) has significantly improved the
      prognosis of HIV(+) in children. Human immunodeficiency-associated lipodystrophy
      syndrome (HALS) is a side effect of HAART seen predominantly in adults and less
      often in children. Leptin is a protein thought to play an important role in body
      composition and has been shown to have immunomodulatory effects. We
      retrospectively studied serum levels of leptin in a cohort of eight HIV-infected
      children followed prospectively before and during HAART and investigated whether
      there is a correlation of these levels with the clinical, immunological, viral or
      nutritional changes observed during treatment in these children. None of our
      children developed HALS. In this small cohort of children, we found that serum
      leptin levels were appropriate to the nutritional status of the patient and that
      leptin/BMI increased in patients who responded to HAART. In conclusion, in HIV(+)
      children during HAART, leptin levels are related to the nutritional status of the
      child.

PMID- 17454844
TI  - Applicability of estimated glomerular filtration rate in stratifying chronic
      kidney disease.
AB  - OBJECTIVE: The aim of this audit was to evaluate the degree of glomerular
      filtration rate (GFR) among inpatients and outpatients in a District General
      Hospital, with special attention given to laboratory testing and impact on health
      delivery. BACKGROUND: UK Chronic Kidney Disease guidelines recommend that
      investigation of renal function should be accompanied by an estimation of GFR
      (eGFR) in order to identify and manage patients with chronic kidney disease
      (CKD). The estimated GFR forms the basis for classification of CKD and
      appropriate action plans for patient management and follow-up. METHOD: A
      retrospective audit of 8160 results from a predominantly British Caucasian
      population was carried out; extracting creatinine results from two isolated
      months in years 2001 and 2004. The estimated GFR (eGFR) was calculated using the
      MDRD formula. The data were classified according to demography, serum creatinine
      and eGFR. Patients from the 2001 database were classified according to eGFR and
      those with a value of <60 mL/min/1.73 m(2) were followed up in 2004. RESULTS: The
      difference in eGFR between the men and women was significantly different with
      medians (confidence intervals) of 80.1 (41-109) and 64.4 (30-84.6) (p<0.0001),
      respectively. There was an inverse association between age and eGFR in both
      genders (p<0.0001), with a decrease in eGFR of around 7 % for each decade
      increase in age. 1926 patients (24 %) of results studied had eGFR <60 mL/min, of
      whom 64 % were females and 36 % males. Follow-up of patients with eGFR<60 mL/min
      from 2001 showed that 4 % progressed to stages 4 and 5 CKD. CONCLUSION: eGFR is
      inversely associated with increasing age and female gender. MDRD derived eGFR
      fails to completely compensate for age and gender variations and thus different
      action limits may be required. Small but significant numbers of patients
      progressed to stages 4 and 5 CKD. Additional clarity in describing "progressive
      fall in eGFR" in the guidelines would improve identification of the population
      most at risk.

PMID- 17454845
TI  - Inflammation and coronary angiography in asymptomatic type 2 diabetic subjects.
AB  - OBJECTIVE: Coronary artery disease (CAD) is prevalent in patients with type 2
      diabetes mellitus (T2DM) and because it is often asymptomatic and extensive in
      comparison with CAD in subjects without diabetes, it represents a diagnostic
      challenge. The objective of the study was to investigate the prevalence of CAD in
      asymptomatic T2DM patients utilizing angiography and to investigate its
      association with cardiovascular (CV) risk factors, the metabolic syndrome and
      markers of inflammation. MATERIAL AND METHODS: Eighty-two patients with T2DM
      without symptoms of CAD, and with >or=1 CV risk factor (hypertension,
      dyslipidaemia, premature familial CAD, smoking or microalbuminuria) underwent a
      diagnostic stress test and coronary angiography irrespective of stress test
      results. Stenosis detected in the main coronary arteries >or=50% of lumen
      diameter was categorized as one-, two- or three-vessel disease. Inflammatory
      markers were analysed in fasting samples. RESULTS: Fifteen men and two women had
      significant CAD (21%) (1-vessel disease, n=10; 2- or 3-vessel disease, n=7).
      Patients with 2- or 3-vessel disease were significantly older and had a longer
      duration of diabetes, but the prevalence of other traditional CV risk factors or
      the metabolic syndrome was similar among those with 1-vessel and those with 2- or
      3-vessel disease. Sensitivity for CAD of the stress test was low (0.35). The mean
      level of the pro-inflammatory marker interleukin-6 was elevated in patients with
      2- to 3-vessel CAD as compared to patients with no or 1-vessel CAD (p<0.05).
      CONCLUSIONS: Significant CAD was found in 21% of asymptomatic patients with T2DM
      with >or=1 CV risk factor. Inflammatory markers may be helpful in identifying
      patients that are likely to have significant CAD, but larger studies are
      warranted.

PMID- 17454846
TI  - Serum ionized magnesium and calcium levels in adult patients with seizures.
AB  - OBJECTIVE: Prior studies have been equivocal about whether or not serum levels of
      the divalent ions calcium and magnesium are altered during different types of
      seizures. Magnesium is a potential modulator of seizure activity because of its
      ability to antagonize the excitatory calcium influx through the N-methyl-D
      aspartate (NMDA) receptor. We hypothesize that serum ionized levels of calcium
      (Ca(2+)) and magnesium (Mg(2+)) would be altered significantly during certain
      types of seizures. MATERIAL AND METHODS: A convenience sample of seizure patients
      presenting to an emergency department (ED) were enrolled in this prospective
      study. Novel ion-selective electrodes were used to measure Ca(2+) and Mg(2+).
      Data were reported as mean values+/-standard deviations. Group comparisons were
      analyzed by ANOVA with post-hoc testing using the Bonferroni, or the Fisher exact
      test, where appropriate, alpha = 0.05 (two-tailed). RESULTS: Forty-nine patients
      with seizure and 32 healthy racially matched controls were included in the study.
      Seizure patients had a significantly (p<0.001) lower mean Mg(2+), but not total
      serum Mg and a significantly (p<0.001) higher Ca(2+)/Mg(2+) ratio than that in
      controls. CONCLUSIONS: We were able to show significantly lower Mg(2+) and higher
      ionized Ca(2+)/Mg(2+) ratios in seizure patients compared with a racially matched
      control group.

PMID- 17454847
TI  - Impaired first-phase insulin response predicts postprandial blood glucose
      increment in patients with recently diagnosed type 2 diabetes.
AB  - OBJECTIVE: The aim of the study was to evaluate the relationship between
      postprandial blood glucose and first-phase insulin response and, furthermore, to
      assess whether the intravenous glucagon stimulation test can be used as a
      predictor for increased postprandial glucose in patients with recently diagnosed
      type 2 diabetes. MATERIAL AND METHODS: Twenty patients with diet-treated type 2
      diabetes, diagnosed within the past 5 years, were included. In random order, on
      three different days, the patients underwent: 1) a standardized meal tolerance
      test, 2) an intravenous glucose tolerance test, and 3) an intravenous glucagon
      stimulation test. The postprandial blood glucose response was defined as the
      incremental area under the blood glucose curve 0-240 min after the meal. RESULTS:
      The first-phase insulin response at an intravenous glucose stimulation test was
      significantly correlated to the postprandial blood glucose increment (R(2)=0.21,
      p<0.05) and the maximal increment in plasma glucose concentration (R(2)=0.40,
      p<0.01) during the meal tolerance test. However, the incremental C-peptide value
      at 6 min in response to intravenous glucagon stimulation did not correlate to the
      postprandial blood glucose increment (R(2)=0.09, p=0.14). CONCLUSION: Impaired
      first-phase insulin response is a significant predictor of the increase in
      postprandial blood glucose in patients with type 2 diabetes in near normal
      metabolic control, whereas beta-cell function, assessed by glucagon stimulation
      test, is not.

PMID- 17454848
TI  - Short-term effects of the TNFalpha antagonist infliximab on the acute phase
      reaction and activities of daily life in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the short-term effects of the tumour necrosis factor
      alpha (TNFalpha) antagonist infliximab on the acute phase reaction and activities
      of daily life (ADL) in patients with rheumatoid arthritis (RA). METHODS: Fourteen
      patients with active RA were treated with an intravenous infusion of 200 mg
      infliximab. The values of the erythrocyte sedimentation rate (ESR), C-reactive
      protein (CRP), fibrinogen, granulocyte count, lymphocyte count, platelet count
      and a patient questionnaire score on ADL, the Health Assessment Questionnaire
      (HAQ), were obtained at baseline and on days 4 and 14. The significance levels
      and effect sizes (ESs) of the changes from baseline were calculated. RESULTS:
      Changes by day 4: The ESs and significance levels were: CRP 1.7, p<0.005;
      lymphocyte count 1.4, p<0.005; fibrinogen 0.9, p<0.005; ESR 0.7, p<0.005; and HAQ
      0.6, p<0.01. Changes by day 14: CRP 1.6, p<0.005; ESR 1.5, p<0.005; fibrinogen
      1.3, p<0.005; lymphocyte count 1.0, p<0.005; granulocyte count 0.7, p<0.05; and
      HAQ 0.6, p<0.05. CONCLUSION: CRP, fibrinogen and ESR showed the largest ESs and
      were thus the most sensitive variables showing the early effect of infliximab in
      this study. The score on ADL (HAQ) showed less ES, but still significant short
      term improvements.

PMID- 17454849
TI  - Phagocyte-derived oxidants and plasma antioxidants in haemodialysed patients.
AB  - OBJECTIVE: Oxidative stress is one of the important complications occurring in
      haemodialysis. The aim of the study was to determine haemodialysis-induced
      changes in oxidative burst of phagocytes and the antioxidative properties of
      plasma. METHODS: Twenty-seven patients and 50 healthy controls were examined.
      Oxidative burst of phagocytes and plasma antioxidative potential were measured
      luminometrically. Concentrations of major plasma antioxidants (vitamin E,
      bilirubin and uric acid) were also determined. RESULTS: Phagocyte
      chemiluminescence was higher in patients before haemodialysis compared with that
      in controls and decreased after haemodialysis compared with predialysis status. A
      significant increase in plasma antioxidative potential and uric acid was found in
      patients before haemodialysis. These parameters decreased after haemodialysis
      compared with both predialysis and control values. CONCLUSIONS: The higher
      generation of phagocyte-derived oxidants and the decline in plasma antioxidative
      properties after haemodialysis confirm insufficient antioxidant defence in
      patients with chronic renal failure.

PMID- 17454850
TI  - Pathophysiological aspects of pulmonary complications of cirrhosis.

PMID- 17454851
TI  - Dysphagia after laparoscopic Nissen fundoplication.
AB  - OBJECTIVE: To investigate the frequency and severity of dysphagia during the
      first 8 weeks after laparoscopic Nissen fundoplication for gastro-oesophageal
      reflux disease. So far, there have been no studies reporting data on day-to-day
      occurrence of dysphagia after laparoscopic fundoplication in a consecutive series
      of patients. This may explain why the frequency of dysphagia varies greatly in
      the literature (4-100%). MATERIAL AND METHODS: Forty consecutive patients,
      undergoing elective laparoscopic Nissen fundoplication, completed a standard
      dysphagia registration diary each day during the first 8 weeks after surgery.
      Patients who preoperatively had suffered from dysphagia were excluded. Thus, none
      of the patients had dysphagia in the 2-month period before surgery. Ten patients
      undergoing elective cholecystectomy served as controls. Data were quantified, and
      a score value of 4 or more was considered bothersome. RESULTS: Thirty-seven
      patients (93%) experienced some degree of dysphagia during the observation
      period. Sixteen patients (44%) had at least one day with annoying dysphagia. The
      dysphagia started 1-2 days after surgery, was most prominent during the first few
      weeks, and subsided in nearly all cases after 5-6 weeks. Two patients with
      persistent dysphagia were treated once with balloon dilatation. None of the
      patients in the control group had dysphagia. CONCLUSIONS: Nearly all patients
      experience some degree of dysphagia after laparoscopic Nissen fundoplication, and
      in nearly half of the patients it is considered annoying. However, even severe
      dysphagia usually disappears within 5-6 weeks. These results suggest a
      conservative attitude for the first 1-2 months after surgery. The data may also
      serve as a background for preoperative information to the patients.

PMID- 17454852
TI  - Sensory and biomechanical properties of the esophagus in non-erosive reflux
      disease.
AB  - OBJECTIVES: To investigate possible differences between patients with non-erosive
      gastroesophageal reflux disease (NERD) and controls in a) sensitivity of the
      distal esophagus after mechanical and thermal stimuli and b) the referred pain
      areas. MATERIAL AND METHODS: Fifteen healthy subjects (mean age 39+/-19.4 years)
      and 13 NERD patients (mean age 44.4+/-21 years) were enrolled in the study. Pain
      evoked by mechanical and thermal stimuli was assessed using a newly designed
      multimodal stimulation probe. RESULTS: The patients were less sensitive to
      mechanical stimulation as assessed by the cross-sectional area (p<0.001) and
      volume (p=0.007). After thermal stimulation, the patients were hypersensitive to
      heat stimuli (p=0.04), whereas no significant difference was seen to cold
      stimuli. The referred pain areas were larger in patients compared with the pain
      areas in controls after mechanical (p=0.03) and heat stimuli (p=0.01), but not
      after cold stimuli. Balloon distension resulted in a significant higher number of
      reactive esophageal contractions in patients as compared with controls (p=0.001).
      CONCLUSIONS: The present study showed that NERD patients were hypersensitive to
      heat stimuli of the esophagus, with an increase in referred pain to the evoked
      visceral pain. The data indicate that peripheral sensitization of heat-sensitive
      pathways together with facilitation of central pain mechanisms are important in
      the pathogenesis of NERD.

PMID- 17454853
TI  - Feeding and colonic distension provoke altered autonomic responses in irritable
      bowel syndrome.
AB  - OBJECTIVE: Alterations in autonomic balance, detectable by heart rate variability
      (HRV) analysis, have been shown to occur after a meal in patients with irritable
      bowel syndrome (IBS). There are few data on changes in sympathovagal responses in
      IBS to other forms of enteric stimulation such as colonic distension. The aim of
      this study was to determine the effects of colonic balloon distension on HRV in
      the fasting and the postprandial state in healthy subjects and in IBS patients.
      MATERIAL AND METHODS: Eight IBS patients and 8 age- and gender-matched healthy
      subjects underwent unsedated descending colonic distension before and after a
      1000 kcal liquid meal. Low- (LF) and high-frequency (HF) HRV band values obtained
      from 2-min ECG segments recorded before and during distension were compared
      between groups, and between fasting and postprandial states. A visual analogue
      scale was used to determine sensation during colonic distension. RESULTS: HF
      values decreased significantly with feeding in IBS patients (p=0.01), but not in
      healthy subjects. The low-to-high frequency (LF/HF) ratio was significantly
      higher postprandially in IBS patients (p=0.02) and, additionally, was decreased
      (p<0.01) with colonic distension in the fed state, independently of colonic
      sensitivity or distending volume. Moreover, changes in the LF/HF ratio with
      distension in the fed versus the fasting state were negatively correlated in IBS
      patients but positively correlated in healthy subjects (both p<0.05).
      CONCLUSIONS: IBS patients demonstrated altered autonomic responses to feeding and
      colonic distension. Further studies should determine whether these alterations
      could explain the postprandial exacerbation of symptoms in IBS.

PMID- 17454854
TI  - Effects of ghrelin on feeding regulation and interdigestive migrating complex in
      rats.
AB  - OBJECTIVE: Ghrelin is an orexigenic peptide with remarkable prokinetic effects.
      However, its mechanisms in regulating feeding and gastrointestinal migrating
      myoelectrical complex (MMC) are not fully understood. The aim of this study was
      to examine the effects of ghrelin on feeding regulation and duodenal motility in
      rats. MATERIAL AND METHODS: Feeding regulation was investigated at different
      times after intravenous injection of ghrelin and its receptor antagonist (D
      Lys3)GHRP-6 in fasted rats. Rats were supplied with a pair of silver bipolar
      electrodes embedded in the duodenal serosa for electromyography. Ghrelin was
      injected intravenously into the rats during the fed state or fasted state. Some
      rats were pretreated with atropine, phentolamine, propranolol, L-arginine, the 5
      hydroxytryptamine3 receptor antagonist ondansetron, and (D-Lys3)GHRP-6. RESULTS:
      Ghrelin had little effect on food intake in the first 30 min after
      administration, but was found to increase feeding during the subsequent hours. (D
      Lys3)GHRP-6 decreased feeding and antagonized the effect of ghrelin. Ghrelin
      induced duodenal MMC after administration in the fed state, and shortened the
      duodenal MMC cycle length and the duration of phase III during fasting. The
      amplitude and frequency of phase III were increased without affecting the
      percentage of phase III in the MMC cycle. Pretreatment with atropine, L-arginine,
      ondansetron, and (D-Lys3)GHRP-6 inhibited the effects of ghrelin. Propranolol and
      phentolamine had little influence on these effects. CONCLUSIONS: Ghrelin appears
      to be closely related to feeding and intestinal motility. The excitatory effects
      of ghrelin are dependent on the cholinergic pathway, and it has a close
      relationship with the NOS-NO or 5-HT pathway. The ghrelin receptor is involved in
      its activities.

PMID- 17454855
TI  - Expression of the genes dual oxidase 2, lipocalin 2 and regenerating islet
      derived 1 alpha in Crohn's disease.
AB  - OBJECTIVE: A global gene expression profile of non-inflamed colonic mucosal cells
      from patients with Crohn's disease (CD) and of colonic mucosal cells from
      controls was performed. MATERIAL AND METHODS: Tissue specimens from
      macroscopically non-inflamed descending colon were obtained colonoscopically from
      33 CD patients and from 17 control subjects. All controls and 10 CD patients were
      medication-free at the time of colonoscopy. The Human Genome U133 Plus 2.0
      GeneChip Array was used for gene profiling. Hybridization data were analysed with
      dChip software. Results were confirmed by real-time reverse transcriptase
      polymerase chain reaction (RT-PCR). Protein product expression of selected genes
      was assessed by immunohistochemistry using the Envision+ visualization technique.
      RESULTS: The expression profile was not homogeneous with the statistical cut
      point settings applied. In comparison with controls, it was found that 19 CD
      patients had three differentially expressed genes, two of them related to the
      innate immune system: dual oxidase 2 on chromosome 15 (DUOX2, fold change 4.1)
      and lipocalin 2 on chromosome 9 (LCN2, fold change 3.1). The third gene,
      regenerating islet-derived 1 alpha (REG1A, fold change 3.9), codes for a
      mitogenic protein; this could not be confirmed by RT-PCR. Medication-free
      patients had no differentially expressed genes as compared with controls.
      Immunohistochemistry indicated that these proteins were produced by epithelial
      cells (REG1A, LCN2) and leucocytes (DUOX2 and LCN2). CONCLUSIONS: As compared
      with controls, non-inflamed colonic mucosal cells contain two up-regulated genes
      related to the innate immune system. Up-regulation of these genes, known to be
      induced by microorganisms, suggests either increased microflora antigenicity or
      an altered function in mucosal barrier defence.

PMID- 17454856
TI  - The insulin-like growth factor (IGF) system and its relation to infliximab
      treatment in adult patients with Crohn's disease.
AB  - OBJECTIVE: Metabolic bone disease (MBD) and muscle wasting (MW) are serious
      complications in adult patients suffering from inflammatory bowel disease. These
      complications may be caused by alterations in the insulin-like growth factor
      (IGF) system. The aim of the present study was to assess changes in the IGF
      system in patients with active Crohn's disease (CD) before and during infliximab
      treatment. MATERIAL AND METHODS: We studied 13 patients with therapy refractory
      CD, treated with infliximab (5 mg/kg body-weight) at baseline and after 2 weeks.
      The IGF system and markers of inflammation were examined at baseline, on days 2-5
      and after 1, 4, and 8 weeks. Ten healthy age- and gender-matched persons served
      as controls. RESULTS: Total IGF-I and IGF binding protein (IGFBP)-3 levels were
      reduced by 36% (p<0.05) and 27% (p<0.001), respectively, compared with those of
      controls, and normalized during the study period. Free IGF-I levels were reduced
      by 46% (p<0.05) compared with those of controls and remained suppressed. IGFBP-2
      levels were increased at baseline by a factor 2.3 compared to controls (p<0.01)
      with partial normalization at the end of the study period. The Crohn's disease
      Activity Index, the Harvey Bradshaw Index, C-reactive protein, orosomucoid and
      albumin reached normal levels during infliximab treatment. CONCLUSIONS: Treatment
      with infliximab normalized circulating levels of total IGF-I and IGFBP-3, and
      partially normalized IGFBP-2, whereas free IGF-I remained suppressed. We suggest
      that the changes in the IGF system may be part of the catabolic state in active
      CD and may have an association with MBD and MW.

PMID- 17454857
TI  - Thymidylate synthase expression in primary colorectal tumours is correlated with
      its expression in metastases.
AB  - OBJECTIVE: Thymidylate synthase (TS) is the rate-limiting enzyme in the synthesis
      of pyrimidine nucleotides and as such a critical target for fluoropyrimidines,
      which are widely used in the treatment of colorectal cancer (CRC). The purpose of
      this study was to investigate TS expression in the primary tumours (PTs) and
      their metastases (M) in advanced CRC. MATERIAL AND METHODS: TS expression was
      determined immunohistochemically in paraffin-embedded biopsies of PT-M pairs in
      39 CRC patients, as related to the clinical data. RESULTS: There was no
      difference in the mean TS index of PTs compared with that of M, 1.25 and 1.14,
      respectively (p=0.12). TS expression of PTs was above the mean more often than
      that of M (61.5% and 41.0%, respectively, p=0.035). High TS expression in PTs was
      significantly related to high expression in M (the Fisher exact test, p=0.001).
      Using the absolute index values, TS expression in PT and M was significantly
      correlated (Pearson R=0.501, p=0.001). In 29/39 (74.3%) pairs, PT and M had
      concordant expression levels (Cohen's kappa 0.508, 95% CI 0.260-0.756, p=0.001;
      intraclass correlation coefficient (ICC) = 0.679, 95% CI 0.358-0.836, p=0.0001).
      No significant association was found between TS expression and any of the
      clinicopathological variables, disease outcome (DFS, DSS) or its response to
      treatment in univariate or multivariate analysis. CONCLUSIONS: Albeit usually
      higher, TS expression in PT was closely correlated with TS expression in M. This
      suggests that measurement of TS in primary CRC accurately predicts TS expression
      in subsequent metastases, which may help in selecting those patients most likely
      to respond to 5-FU-based regimens.

PMID- 17454859
TI  - Survival impact of delayed treatment in patients with hepatocellular carcinoma
      undergoing locoregional therapy: is there a lead-time bias?
AB  - OBJECTIVE: Many reports indicate the importance of active treatment for
      hepatocellular carcinoma (HCC), but there are few studies available that address
      the impact of delayed therapy on survival or take the lead-time bias into
      account. The objective of this study was to investigate whether patients with
      delayed locoregional therapy for HCC truly have a shortened survival from the
      time of diagnosis. MATERIAL AND METHODS: Survival rates were compared between 48
      HCC patients with treatment delay and 96 age- and gender-matched controls without
      delay. All patients underwent transarterial chemoembolization or percutaneous
      ethanol or acetic acid injection for HCC. Treatment delay was defined as a >2
      months' time interval between diagnosis and treatment. RESULTS: Baseline
      comparison showed that patients with treatment delay had higher scores in the
      model for endstage liver disease compared with those of patients without delay
      (12.3+/-1.8 versus 11.1+/-2.5, p=0.01). In the Cox multivariate model, advanced
      cancer stage (relative risk (RR): 2.66, p=0.001), Child-Turcotte-Pugh class B
      (RR: 3.81, p<0.001), tumor size >5 cm (RR: 2.02, p=0.011) and treatment delay
      (RR: 2.91, p=0.001) were independent poor prognostic predictors. Among patients
      with treatment delay, disease progression was registered in 30 (63%) patients.
      Patients with prolonged treatment delay (>3 months) were more likely to have
      tumor progression (p=0.013). In the Cox model, a treatment delay of >3 months
      independently predicted a poor rate of survival (RR: 3.67, p=0.002). CONCLUSIONS:
      Delayed HCC treatment is linked with shortened overall survival unrelated to the
      lead-time bias in patients undergoing locoregional therapy. Prolonged treatment
      delay of more than 3 months in these patients may worsen the long-term outcome.

PMID- 17454858
TI  - Modified Irinotecan/5FU/Leucovorin therapy in advanced colorectal cancer and
      predicting therapeutic efficacy by expression of tumor-related enzymes.
AB  - OBJECTIVE: To evaluate the efficacy and safety of a regimen using Irinotecan, 5FU
      and Leucovorin for patients with advanced or recurrent colorectal cancer.
      MATERIAL AND METHODS: Irinotecan (75 mg/m(2)) was administered biweekly, while
      5FU (600 mg/m(2)) and Leucovorin (250 mg/m(2)) were administered weekly, for 6
      weeks. RESULTS: The 21 consecutive patients subjected to this regimen showed a
      good response rate (43%) with minimal toxicity (incidence of grade 3/4:
      leukopenia and neutropenia, 5%, respectively, and vomiting, 10%). The mean
      survival time of all 21 patients was 15.7 months. This regimen could be a valid
      option for patients with advanced colorectal cancer, especially those seeking a
      good QoL (quality of life) for the remainder of their lives. We evaluated the
      expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD),
      thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT) mRNAs,
      and sialyl Lewis X on formalin-fixed, paraffin-embedded colorectal tumor samples.
      Expression of TS mRNA or sialyl Lewis X was negatively correlated with the
      response from chemotherapy. Patients with low DPD mRNA expression in the tumor
      showed a significant longer survival than those with high expression. In patients
      with high TP mRNA expression, there was a tendency towards a high incidence of
      leukopenia. CONCLUSIONS: Some predictive factors elucidated in this study could
      contribute to the progress of the tumor-biology based, individualized
      chemotherapy for colorectal cancer patients.

PMID- 17454860
TI  - Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphism in alcohol
      liver cirrhosis and alcohol chronic pancreatitis among Polish individuals.
AB  - OBJECTIVE: To investigate the effects of ADH and ALDH gene polymorphism on the
      development of alcoholism, alcohol liver cirrhosis and alcohol chronic
      pancreatitis among Polish individuals. MATERIAL AND METHODS: We determined the
      allele and genotype of ADH2, ADH3 and ALDH2 in 198 subjects: 57 with alcohol
      cirrhosis, 44 with alcohol chronic pancreatitis and 43 "healthy alcoholics"; 54
      healthy non-drinkers served as controls. Genotyping was performed using the
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      method on white cell DNA. RESULTS: In the population examined the ADH2*1 allele
      frequency was 97.97%. The tests did not show the ADH2*3 allele. The ADH3*1 allele
      frequency was 57.07%. The ADH2*1 and the ADH3*1 alleles were statistically more
      common among patients who abuse alcohol in comparison with the controls. The
      ADH2*2 allele was not detected in any of the patients with chronic alcohol
      pancreatitis. The ADH2*1/*1 and the ADH3*1/*1 genotypes were statistically
      significantly more common among the patients who abuse alcohol than in the
      control group. All patients were ALDH2*1/*1 homozygotic. Patients with the ADH3*1
      allele and the ADH3*1/*1 genotype started to abuse alcohol significantly earlier
      in comparison to the patients with the ADH3*2 allele and the ADH3*2 /*2 genotype.
      CONCLUSIONS: In the Polish population examined, the ADH3*1 allele and the
      ADH3*1/*1 genotype are conducive to the development of alcoholism, alcohol liver
      cirrhosis and alcohol chronic pancreatitis. However, the ADH2*2 allele is likely
      to protect against these conditions. Genetic polymorphism of ALDH2 shows no
      correlation with alcohol addiction or alcohol cirrhosis and alcohol chronic
      pancreatitis. The ADH3*1 allele and the ADH3*1/*1 genotype are conducive to
      alcohol abuse starting at a younger age.

PMID- 17454861
TI  - Liver involvement in acute vaso-occlusive crisis of sickle cell disease:
      prevalence and predisposing factors.
AB  - OBJECTIVE: To study the prevalence and predisposing factors of liver involvement
      in sickle cell disease (SCD) of patients with acute vaso-occlusive crisis.
      MATERIAL AND METHODS: We prospectively evaluated 41 consecutive patients (44% M,
      median age 39 years, range 16-56 years) with homozygous (HbSS; 12 cases) or
      sickle cell-beta thalassemia (HbSbeta-thal; 29 cases), admitted to our Medical
      Department in the period 2002 to 2004. Severity of crisis was graded by in-house
      modified APACHE score; presence of asplenia or functional hyposplenism was also
      considered. Hematological and biochemical parameters including various relevant
      enzymes/isoenzymes were followed daily. RESULTS: Despite the fact that only 9
      patients (22%) presented with acute painful hepatomegaly, liver involvement was
      evident in 16 (39%); hepatocellular-type injury was found in 1 patient,
      cholestatic in 8, and mixed in 7. Severity of crisis was not related to liver
      involvement (score 20.6 versus 18.2), but liver involvement occurred in the
      presence of normal spleen function (p<0.001) and platelet counts <500,000/mm(3)
      (p<0.001) were. Patients with liver involvement, compared with those without, had
      higher total and direct bilirubin levels (4.3 versus 2.9 mg/dL, p=0.050; 1.9
      versus 0.8 mg/dL, p=0.010, respectively), lower hematocrit (19% versus 23%,
      p=0.030) and longer hospitalization (10 versus 6.3 days, p<0.001). CONCLUSIONS:
      In SCD, there is a 39% prevalence of acute veno-occlusive involvement of the
      liver, a figure that is much higher than previously reported. The type of injury
      is mostly mixed hepatocellular-cholestatic or purely cholestatic and its course
      is usually benign. Liver involvement occurs more often in patients with normal
      spleen function and is not associated with the overall severity of the acute
      episode, both observations being unreported previously.

PMID- 17454862
TI  - Ultra thin needle histology may have impact in diagnosing chronic pancreatitis.
AB  - OBJECTIVE: Diagnosis of chronic pancreatitis is usually based on symptoms, ductal
      or parenchymal changes in imaging studies and function tests, but seldom on
      histology. Because the diagnosis of mild chronic pancreatitis is especially
      difficult, better tools to distinguish between chronic pancreatitis and normal
      pancreas are needed. Nowadays, cutting needles as thin as the widely used
      puncture needles are available. Using resected specimens, our aim was to evaluate
      whether these ultra-thin needles can take samples for histology that would allow
      verification of the diagnosis of chronic pancreatitis, with reference to a
      pancreatic wedge biopsy as the "gold standard". MATERIAL AND METHODS: Fifty
      patients underwent pancreatic resection for various reasons. Two 20 G needle
      biopsies (outer diameter 0.8 mm, study biopsies) and a 5 x 5-mm wedge biopsy
      (reference biopsies) were taken from the same site of the specimen, avoiding
      possible neoplastic areas in the specimen. The samples were analyzed for the
      presence inflammation and fibrosis, both graded 0-3, as well as for any
      neoplastic changes without knowledge of the medical history, operative findings
      or final histology. RESULTS: The reference biopsy showed normal tissue in 19
      (38%) patients, chronic pancreatitis in 29 (58%) and only mild fibrosis (Grade 1)
      in 2 (4%) patients. In one patient the needle biopsy was insufficient for
      analysis. There was agreement between ultra-thin needle histology and the control
      specimen in 45/49 (92%) patients (correlation coefficient 0.9). Two biopsies of
      chronic pancreatitis and one mild fibrosis were misclassified as normal tissue,
      while one chronic pancreatitis biopsy was misclassified as an adenocarcinoma. The
      sensitivity of needle biopsy for chronic pancreatitis was 89%, specificity 100%
      and accuracy 94%. CONCLUSIONS: Ultra-thin needle histology correlates well with
      the pancreatic wedge biopsy. Thus, these encouraging results warrant further
      clinical studies of different grades and types of chronic pancreatitis.

PMID- 17454863
TI  - New method of evaluating gastric mucosal blood flow by ultrasound.
AB  - OBJECTIVE: Evaluation of gastrointestinal blood flow is important. However, a non
      invasive measurement method has not yet been established. The aim of this study
      was to compare measurement of normal gastric mucosal blood flow by advanced
      dynamic flow (ADF) flash echo imaging (FEI) with intravenous Levovist with
      measurement by laser Doppler flowmetry (LDF) to clarify the usefulness of ADF-FEI
      and thereby consider its feasibility as a non-invasive gastric mucosal blood flow
      measurement method. MATERIAL AND METHODS: Measurements were obtained in 25 beagle
      dogs (8-month-old males, body-weight, 10.6+/-1.3 kg, mean+/-SD). After insertion
      of a gastrointestinal endoscope, gastric mucosal blood flow at the greater
      curvature of the corpus was measured by LDF, and images of gastric mucosal blood
      flow were obtained by ADF-FEI (frequency; 4.7 MHz) with intravenous injection of
      Levovist (30 mg/kg). ADF-FEI images were transferred to a personal computer. A
      region of interest was set on the mucosa of the greater curvature of the corpus,
      and a time intensity curve (TIC) was plotted from the measured echo intensities.
      The area under the curve (AUC) calculated from the TIC and the median flow
      determined by LDF were analyzed and compared. RESULTS: Evaluation of normal
      gastric mucosal blood flow by ADF-FEI was possible in all animals. There was a
      strong, significant correlation between gastric mucosal blood flow measured by
      LDF and the AUC obtained by ADF-FEI (r=0.869, p<0.0001). CONCLUSIONS: Gastric
      mucosal blood flow can be accurately measured by ADF-FEI with intravenous
      Levovist injection.

PMID- 17454864
TI  - Differently charged polypeptides in the prevention of post-surgical peritoneal
      adhesions.
AB  - OBJECTIVE: Peritoneal adhesions develop after almost all surgical interventions
      in the abdomen. We have developed an efficient treatment against post-surgical
      adhesions consisting of a combination of positively charged poly-L-lysine and
      negatively charged poly-L-glutamate. The aim of the present study was to further
      develop the concept of applying oppositely charged polypeptides in the prevention
      of adhesion formation, by evaluating different doses of the peptides, alterations
      in the way of administration, and also testing alternative components. MATERIAL
      AND METHODS: Eighty-five NMRI mice were divided into six groups. A standardized
      peritoneal injury model was used. The groups received physiologic sodium
      chlorine, poly-L-lysine+poly-L-glutamate, low molecular weight poly-L-lysine+poly
      L-glutamate, locally administered poly-L-lysine+poly-L-glutamate, in vitro mixed
      poly-L-lysine+poly-L-glutamate and poly-L-arginine+poly-L-glutamate,
      respectively. After 7 days, the extent of adhesion formation was determined
      during relaparotomy and was expressed as the mean percentage of the total wound
      length. RESULTS: A significant decrease (p <0.001) in the peritoneal adhesion
      rate was detected in all groups, with the exception of the group administered
      poly-L-arginine. Among those animals that received poly-L-lysine and poly-L
      glutamate, the low dose of poly-L-lysine administration resulted in the most
      pronounced anti-adhesive effect. CONCLUSIONS: The most effective polypeptide
      combination was poly-L-lysine and poly-L-glutamate, also showing effectiveness
      when used at low doses and by local application. The differences in adhesion
      prevention and the possible underlying mechanisms are discussed and the key role
      of poly-L-lysine is elucidated.

PMID- 17454865
TI  - Endoscopic-ultrasound-guided endoscopic transmural drainage of pancreatic
      pseudocysts and abscesses.
AB  - OBJECTIVE: Surgery is the traditional treatment for symptomatic pancreatic
      pseudocysts and abscesses, but morbidity and mortality are still too high.
      Minimally invasive approaches have been encouraged. The aim of this study was to
      evaluate the results of the endoscopic-ultrasound-guided (EUS) endoscopic
      transmural drainage of these pancreatic collections. MATERIAL AND METHODS: In
      this retrospective review of consecutive cases from a single referral centre,
      cystogastrostomy and cystoduodenostomy were created with an interventional linear
      echoendoscope under endosonographic and fluoroscopic control by the endoscopic
      insertion of straight or double pigtail stents. RESULTS: Fifty-one symptomatic
      patients (33 men; mean age 58 years) were submitted to 62 procedures from January
      2003 to December 2005. EUS-guided drainage was successful in 48 (94%) patients.
      Only three patients needed surgery. There were two procedure-related
      complications managed clinically. During a mean follow-up of 39 weeks, recurrence
      due to migration or obstruction of the stent was 17.7%. All these cases were
      submitted to a new session of endoscopic drainage. There was no mortality.
      Complications were more frequent in patients with a recent episode of acute
      pancreatitis (38.5% versus 10%; p=0.083). The endoscopic approach was not more
      hazardous for abscesses in regard to complications rate (19% versus 16.6%;
      p>0.05). In abscesses, a nasocystic drain did not decrease the complications rate
      (27% versus 13%; p=0.619), but the placement of 2 stents did decrease this rate
      (18% versus 20%; p>0.05), although increased it in pseudocysts (40% versus 13%;
      p=0.185). CONCLUSIONS: Endoscopic transmural drainage is a minimally invasive,
      effective and safe approach in the management of pancreatic pseudocysts and
      abscesses.

PMID- 17454866
TI  - Microscopic colitis associated with lansoprazole: report of two cases and a
      review of the literature.
AB  - Microscopic colitis causes chronic watery diarrhea. Many cases may be induced by
      medications, and lansoprazole, a commonly used proton-pump inhibitor, has been
      associated with collagenous colitis and lymphocytic colitis, the two subtypes of
      microscopic colitis. Two cases of collagenous colitis associated with
      lansoprazole are reported, both in older female patients, who each developed
      profuse watery diarrhea within weeks of starting lansoprazole to treat upper
      digestive disorders. Colonoscopy was normal and biopsies demonstrated typical
      features of collagenous colitis. There was a rapid clinical improvement upon
      switching from lansoprazole to rabeprazole, and histological normalization on
      follow-up biopsies. A review of the literature showed 14 other cases of
      lansoprazole-related microscopic colitis. There are no reported cases of
      microscopic colitis associated with other proton-pump inhibitors, suggesting a
      pathophysiologic mechanism specific to the pharmacology of lansoprazole.
      Clinicians must be aware of this association when prescribing this medication;
      when a patient taking lansoprazole develops diarrhea, substituting an alternative
      proton-pump inhibitor should allow resolution of the diarrhea.

PMID- 17454867
TI  - Treatment of hepatic hydrothorax with vasoconstrictor drugs.

PMID- 17454868
TI  - Cholecystocolonic fistula with impacted sigmoid gallstone mimicking malignant
      obstruction of the sigmoid colon.

PMID- 17454869
TI  - Efficacy of s-type stents for the treatment of the main pancreatic duct stricture
      in patients with chronic pancreatitis.

PMID- 17454870
TI  - Lymphocytic colitis in a patient with psoriasis responsive to budesonide.

PMID- 17454871
TI  - Gilbert's syndrome phenotypically expressed as Crigler-Najjar syndrome type II.

PMID- 17454872
TI  - Magnification endoscopy with acetic acid in Barrett's esophagus.

PMID- 17454873
TI  - Acute cholecystitis: A surgical challenge.

PMID- 17454874
TI  - Gastric epithelial cell proliferation and cagA status in Helicobacter pylori
      gastritis at different gastric sites.
AB  - OBJECTIVE: Helicobacter pylori infection causes hyperproliferation which is
      believed to predispose to the development of gastric carcinoma. The aim of this
      study was to analyze epithelial cell proliferation topographically in H. pylori
      gastritis in relationship to cagA status. MATERIAL AND METHODS: The proliferative
      index (PI: Ki-67-labeled nuclei/total number of foveolar nuclei) was determined
      in gastric mucosa biopsies taken at the antrum (lesser and greater curvatures),
      incisura, and corpus (greater curvature) from 78 patients with H. pylori
      gastritis and 20 H. pylori-negative patients. H. pylori and cagA status were
      determined by polymerase chain reaction (PCR) and serology. RESULTS: PIs were
      significantly higher in H. pylori- and cagA-positive patients, in comparison with
      H. pylori- and cagA-negative patients, at all sites (p<or=0.002 and p<or=0.009)
      and in the antrum in comparison to the corpus, in both H. pylori-negative
      (p=0.04) and positive patients (p<10(-3)). At the antral lesser curvature, PIs
      were higher than in all the other sites, both in H. pylori- (p<or=0.002) and cagA
      positive groups (p<or=0.02). The PI correlated directly and significantly with
      inflammation in infected patients (r=0.45, p<10(-3)) and in cagA-positive
      patients (r=0.41, p=0.005). The PI was significantly higher in the antrum of
      infected patients with atrophy (p=0.03) and intestinal metaplasia (p=0.05) than
      in those without atrophy and intestinal metaplasia, respectively. CONCLUSIONS: We
      demonstrated that H. pylori infection and cagA-positive strains promote
      epithelial proliferation that was correlated with host inflammatory reaction and
      mostly at the antral lesser curvature, which is recognized as the area where most
      carcinomas arise.

PMID- 17454875
TI  - Secretion of total pepsin and pepsin 1 in healthy volunteers in response to
      pentagastrin and to insulin-induced hypoglycaemia.
AB  - OBJECTIVE: Human gastric juice contains a multiplicity of proteinases, and one
      enzyme (pepsin 1) is increased in patients with peptic ulcer disease. However,
      little is known about its secretion in health. The purpose of this study was to
      determine the pepsin 1 content in relation to the total pepsin of human gastric
      juice in healthy volunteers and the effect of different stimuli on secretion.
      MATERIAL AND METHODS: Human gastric juice from healthy volunteers was collected
      at 10-min intervals over a period of 30 min basally and up to 60 min after
      continuous intravenous pentagastrin administration (n=13) or insulin-induced
      hypoglycaemia (n=11). Pepsin 1 was measured by semiquantitative agar gel
      electrophoresis and the total pepsin as the proteolytic activity calibrated
      against pig pepsin A. RESULTS: Pepsin 1 was present in 23 out of 24 basal gastric
      juice samples at a mean concentration of approximately 12 microg/ml. During
      continuous intravenous pentagastrin to 11 subjects for 60 min, the mean
      concentration and secretion rates per minute rose to 24 microg/ml and 122
      microg/min at 60 min; the proportion of pepsin 1 to total pepsin was 2.8% in
      basal secretions increasing to 7.8% in the 60 to 70-min samples. Following
      intravenous insulin administration to 11 subjects, the mean concentration and
      secretion rates of pepsin 1 rose to 33 microg/ml and 127 microg/min at 60 min:
      the proportion of pepsin 1 to total pepsin was 0.8% in basal secretions and 3.1%
      in the 50 to 60-min samples. CONCLUSIONS: Both pentagastrin and hypoglycaemia
      caused similar maximal secretion rates of pepsin 1, but hypoglycaemia caused
      greater secretion rates of total pepsin. The maximum concentrations and secretion
      rates of pepsin 1 occurred at different times from those of total pepsin and
      there is a threshold of total pepsin secretion below which pepsin 1 was not
      released.

PMID- 17454876
TI  - Deficient activity of mammalian prolyl oligopeptidase on the immunoactive peptide
      digestion in coeliac disease.
AB  - OBJECTIVE: Gliadin digestion-resistant peptides are harmful in coeliac disease
      (CD), and initiate an autoimmune reaction that cause a cascade of symptoms. The
      role of the endogenous prolyl oligopeptidase (POP) is still not clear, and its
      activity over gliadin immunoactive peptides has not been fully established. Our
      objective was therefore to determine the endogenous POP protein level, tissue
      distribution and total activity in normal and CD epithelia, to evaluate tissue
      peptidase activity over gliadin peptides, and compare this with activities of
      mammalian POP and rat intestinal extracts. MATERIAL AND METHODS: POP was assayed
      in biopsy preparations enzymatically and by Western blot analysis. Distribution
      was studied by immunohistochemistry using a specific POP antibody. Peptide
      cleavage was followed by mass spectroscopy-high-performance liquid chromatography
      (MS-HPLC). RESULTS: There was no difference in POP activity between normal and CD
      samples, but those from active CD subjects had an even higher ability to degrade
      the 33-mer peptide than those from treated CD and healthy humans. POP locates
      intracellularly in epithelia, similarly to dipeptidyl peptidase IV (DPPIV), but
      the latter is clearly found in normal microvilli but less so in diseased
      microvilli. Mammalian POP is unable to digest 33-mer peptide, which, conversely,
      is a POP inhibitor. Rat intestine is more effective than human intestine in
      cleaving the 33-mer peptide. However, the products are still harmful epitopes. A
      surplus of POP eliminates 12-mer and 19-mer peptide products. CONCLUSIONS: The
      results rule out a causative role of POP in the pathogenesis of CD and strongly
      suggest that other peptidases are needed to eliminate gliadin-derived,
      immunoactive and toxic peptides larger than 33-mer, which is a POP inhibitor.

PMID- 17454877
TI  - Inflammatory bowel disease in relation to contact allergy: a patient-based study.
AB  - OBJECTIVE: Inflammatory bowel disease (IBD) has previously been investigated with
      relation to allergic conditions; however, diverging results were found and there
      are only a few small studies focusing on delayed hypersensitivity. The aim of
      this study was to investigate whether there was an association between contact
      allergy (CA), which is a type IV hypersensitivity reaction of the skin, and IBD.
      MATERIAL AND METHODS: A database consisting of a cohort of 13,315 patients, patch
      tested between 1985 and 2003, was linked with the Danish National Patient
      Registry using a unique personal identifier number. The patients were patch
      tested at a dermatology department with a long history of research in CA. By
      record linking with the Danish National Patient Registry, patients were
      identified who had either an International Classification of Disease (ICD) code
      for Crohn's disease (CD) or an ICD code for ulcerative colitis (UC) diagnosis.
      Using logistic regression, with the result of the patch test as the dependent
      variable, we calculated the odds ratios for IBD, CD and UC, adjusted for gender
      and age. RESULTS: An inverse association between CA and IBD was found, odds ratio
      adjusted for age and gender 0.71 (CI 95% 0.53-0.94), which is mainly the result
      of an inverse association between CA and CD, odds ratio adjusted for age and
      gender 0.42 (CI 95% 0.23-0.76). CONCLUSIONS: The association found between CA and
      IBD might be related to shared genetic factors or common environmental
      determinates. It may also be that having either disease result in skewness of the
      immune system might lead to an inverse disease association.

PMID- 17454878
TI  - Predicting the need for surgery in Crohn's disease with contrast harmonic
      ultrasound.
AB  - OBJECTIVE: Harmonic flash echo imaging (H-FEI), an intermittent scanning method
      using injection of Levovist, enables the evaluation of microperfusion of the
      gastrointestinal wall. The aim of this study was prospectively to investigate the
      relationship between bowel blood flow and the likelihood of the need for surgery
      in 70 patients with active Crohn's disease (CD), using conventional
      ultrasonography (US) and H-FEI. MATERIAL AND METHODS: For H-FEI, Levovist
      injection was followed by scanning of the bowel segment of interest with
      intermittent harmonic imaging for 2 min (interval, 4 s; transmission pulse at 2.3
      MHz; reception at 4.6 MHz). We calculated the mean echo-intensity for the bowel
      wall showing strongest opacity in the FEI series for each patient. Maximum bowel
      wall thickness, wall stratification, maximum echo-intensity obtained by H-FEI, CD
      activity index, and C-reactive protein concentration were compared between
      patients treated successfully with medication after H-FEI (group M) and those who
      proved to need surgery (group S). RESULTS: No significant differences in clinical
      variables were evident between groups M (n=45) and S (n=25). The subsequent need
      for surgery was significantly indicated by multivariate analysis, showing loss of
      stratification in the bowel wall (odds ratio (OR)=5.98, 95% confidence interval
      (CI)=1.4-25.1, p=0.015) and high echo-intensity according to H-FEI (OR=1.02,
      CI=1.005-1.034, p=0.007). CONCLUSION: In active CD, patients with bowel segments
      showing a loss of stratification and rich perfusion by H-FEI are likely to need
      surgical treatment.

PMID- 17454879
TI  - Microsatellite instability in long-standing ulcerative colitis.
AB  - OBJECTIVE: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon
      associated with a high risk of developing colorectal cancer. Several genetic
      alterations have been documented in dysplasia and cancer developing in UC.
      Concerning microsatellite instability (MSI), many contradictory results have been
      published. We therefore analysed a large, well-characterized UC material for MSI
      to elucidate its significance in long-standing UC. MATERIAL AND METHODS: From 33
      patients, a total of 159 microdissected lesions and 165 mucosa samples obtained
      adjacent to the tissue blocks were analysed for MSI using the five standard
      markers recommended by the National Cancer Institute; D2S123, D5S346, D17S250,
      BAT-25 and BAT-26. In addition, 12 of the patients were investigated by a mini
      satellite marker at the D1S7 locus. RESULTS: High-level MSI (MSI-H) was detected
      in one villous adenoma with high-grade dysplasia and right-sided location. This
      represents 3.6% (1/28) of dysplastic mucosa investigated. No other lesions showed
      MSI in the five standard markers or at the D1S7 locus. CONCLUSIONS: This study
      suggests that MSI is rare in UC-related neoplasia as well as non-neoplastic
      lesions, and does not contribute to the development of dysplasia.

PMID- 17454880
TI  - Crohn's disease intestinal CD4+ T cells have impaired interleukin-10 production
      which is not restored by probiotic bacteria.
AB  - OBJECTIVE: Crohn's disease (CD) has been associated with low mucosal interleukin
      (IL)-10 production, but the mechanism behind this deficiency remains unclear. The
      aim of this study was to investigate IL-10 and interferon (IFN)-gamma production
      in intestinal CD4+ T cells from CD patients and healthy volunteers (HV) and to
      examine how this was affected by bacterial products and the presence or absence
      of autologous dendritic cells. MATERIAL AND METHODS: We cultured intestinal CD4+
      T cells from CD patients (n=9) and HV (n=6) and differentiated dendritic cells
      from their peripheral monocytes. Intestinal T cells were stimulated with
      Lactobacillus strains or autologous intestinal bacteria in the presence or
      absence of dendritic cells. IL-10 and IFN-gamma were measured on day 4. RESULTS:
      When there were autologous dendritic cells present, CD intestinal T cells
      produced high levels of IFN-gamma (mean 6.4 ng/ml+/-standard error of the mean
      1.1 ng/ml) but low levels of IL-10 (0.7 ng/ml+/-0.1 ng/ml). In contrast, HV
      intestinal T cells produced less IFN-gamma (3.9 ng/ml+/-0.8 ng/ml, p=0.06) and
      more IL-10 (4.6 ng/ml+/-0.9 ng/ml, p=0.0001) than CD intestinal T cells. Co
      culture with Lactobacilli failed to revert this imbalance in CD, but tended to do
      so in HV. When there were no dendritic cells, CD intestinal T cells responded to
      autologous bacteria with an increased IFN-gamma production (2.3+/-1.3 ng/ml)
      compared with HV intestinal T cells (0.3+/-0.2 ng/ml). CONCLUSIONS: Crohn's
      disease intestinal CD4+ T cells display a pro-inflammatory cytokine profile with
      impaired production of the regulatory cytokine IL-10. Tolerogenic bacteria
      (Lactobacilli) failed to restore this regulatory defect.

PMID- 17454881
TI  - Clinical course in Crohn's disease: results of a five-year population-based
      follow-up study (the IBSEN study).
AB  - BACKGROUND: There are few population-based, prospective studies on the clinical
      course in patients with Crohn's disease (CD). AIM: To extend the observation
      period in a population-based prospective study (the IBSEN study) to find out more
      about the initial 5-year clinical course in CD patients and to relate the
      findings to the Vienna classification. METHODS: All patients diagnosed with
      inflammatory bowel disease (IBD) in southeastern Norway in the 4 years 1990-1993
      were followed prospectively. The patients were invited to a systematic follow-up
      visit at their local hospital 1 and 5 years after inclusion in the study. The
      visits included a structured interview, a clinical examination and colonoscopy.
      RESULTS: Out of 843 patients initially diagnosed with IBD, 200 patients with
      definite CD were alive and had sufficient data for analysis 5 years after
      diagnosis. Changes in disease localization and behaviour in relation to the
      Vienna classification were observed in 27 (13.5%) and 35 patients (17.5%),
      respectively. During the observation period, 56 patients (28%) underwent surgery
      with intestinal resection, and half of these had disease localized in the
      terminal ileum. At the time of the 5-year visit, oral sulfasalazin and 5
      aminosalicylic acid (5-ASA) were the most frequently used medications (by 54% of
      the patients), while oral glucocorticosteroids and azathioprine were being used
      by 25% and 13%, respectively. Seventy-two percent of the patients had taken oral
      glucocorticosteroids at some time in the course of the 5-year period. The
      majority of the patients had intestinal symptoms at 5 years, but only 16% had
      symptoms that interfered with everyday activities. Fourteen percent of the
      patients had had a relapse-free 5-year course; however, relapse was not related
      to the initial Vienna classification. When the patients described the clinical
      course, 44% reported an improvement in symptoms during the follow-up period.
      CONCLUSIONS: The 5-year clinical course in an unselected cohort of CD patients
      was mostly mild. The frequency of surgery was lower than that observed in other
      studies and only a minority of the patients had symptoms that interfered with
      everyday activities 5 years after the initial diagnosis. The Vienna
      classification predicted the risk of surgery, but did not predict symptoms at 5
      years, relapses during the observation period or the course of disease as
      described by the patients.

PMID- 17454882
TI  - Prevention of colorectal cancer by colonoscopic surveillance in families with
      hereditary colorectal cancer.
AB  - OBJECTIVE: In recent years persons at risk for colorectal cancers (CRC) have been
      subjected to follow-up with colonoscopy in many centres. There is, however,
      limited knowledge about the effect of such interventions. The objective of this
      study was to report the results of our observations during the past 15 years.
      MATERIAL AND METHODS: Healthy persons were included in the study according to
      their family history of CRCs, and prospectively followed with colonoscopies.
      RESULTS: Altogether, 1133 individuals were included and observed for a total of
      3474 follow-up years from the first to the last colonoscopy initiated by our
      activity. Mismatch repair (MMR) mutations were detected in 6.5% of cases. A total
      of 1383 polyps were removed, 72% were less than 5 mm in diameter. Findings were
      scored as hyperplastic polyps (n=887), adenomas with mild to moderate dysplasia
      (n=460), adenomas with high-grade dysplasia (n=30) and cancers (n=6). Two cancers
      were observed after the first colonoscopy, compared with 2.6 expected by chance
      and more than 20 expected under the hypothesis of predominant inherited diseases
      in the families. Observed annual incidence rates for adenomas were similar in all
      groups, while in the mutation carriers there was a higher frequency of
      progression to severe dysplasia or infiltrating cancer. CONCLUSIONS: A simple
      explanation for the combined findings may be that all selected families had a
      similar tendency to produce adenomas, while mutation carriers more frequently
      demonstrated dysplasia/cancer in the adenomas. The low annual incidence rates for
      CRC indicated that the removal of adenomas may have prevented cancers.

PMID- 17454883
TI  - Pathology findings and validation of gastric and esophageal cancer cases in a
      European cohort (EPIC/EUR-GAST).
AB  - OBJECTIVE: Cardia, non-cardia and intestinal and diffuse subtypes of gastric
      cancer may have different trends and etiological factors. However, the available
      information is not always collected in population cancer registries, and
      heterogeneous criteria have been applied for the histopathological classification
      of tumors. We describe the pathological features of incident gastric and
      esophageal cancers identified within the European Prospective Investigation into
      Cancer and Nutrition (EPIC). MATERIAL AND METHODS: In an investigation on gastric
      and esophageal cancer (EUR-GAST) in the EPIC project, a validation study of
      diagnoses reported by EPIC centers was conducted by a European panel of
      pathologists. Original pathology reports, stained slides of tumors and the
      respective paraffin blocks were requested from the centers. RESULTS: The whole
      series encompassed 467 cancer cases (gastric and esophageal cancers). Material
      was available for histopathological validation in 263 cases (56%); in the
      remaining cases, information was retrieved from the original reports (n=110; 24%)
      or codes provided by the EPIC centers (n=94; 20%). Among cases submitted to
      histopathological validation reported originally as unknown histotype or unknown
      site, a specific diagnosis was made in 95% and 74% of the cases, respectively. In
      cases for which only the original reports were available, the respective
      percentages were 46% and 67%. Gastric adenocarcinomas were classified according
      to site (cardia (29.4%), non-cardia (48.2%) and unknown (22.4%)) and histological
      type (intestinal (33.4%), diffuse (33.7%) and mixed, unclassified or unknown
      (32.9%)). Frequency of cardia was higher in Northern countries (35%) than in
      Mediterranean countries (18%). CONCLUSIONS: In addition to providing
      epidemiological data within the EPIC cohort on gastric and esophageal
      adenocarcinomas, the results reported here confirm the relevance of a validation
      study, notably for multicenter studies.

PMID- 17454884
TI  - Lack of association between genetic polymorphisms in cytokine genes and disease
      expression in patients with hereditary non-polyposis colorectal cancer.
AB  - OBJECTIVE: Hereditary non-polyposis colorectal cancer (HNPCC) is caused by
      germline mutations in DNA mismatch repair (MMR) genes and is characterized by
      familial aggregations of early-onset epithelial cancers. Inflammatory cells
      produce an attractive environment for tumour growth since reactive oxygen and
      nitrogen species generated by inflammatory cytokine induction can cause damage to
      DNA and proteins. In this study the objective was to investigate single
      nucleotide polymorphisms (SNPs) in cytokine genes to assess their impact on
      disease expression in individuals diagnosed with HNPCC. MATERIAL AND METHODS: DNA
      samples from 220 participants diagnosed with HNPCC were genotyped for SNPs in IL
      6, IL-1beta, TNF-alpha, IFN-gamma, IL-10, IL-4 and IL-1RN. The association
      between the polymorphisms and disease characteristics, i.e. affected or
      unaffected with colorectal cancer (CRC) and age of diagnosis of CRC, was tested
      with the Pearson chi2 test and by Kaplan-Meier survival analysis. RESULTS: There
      was no significant difference between CRC patients and unaffected MMR gene
      mutation carriers for any of the SNPs studied and the Kaplan-Meier survival
      analysis showed no significant difference between age of diagnosis of CRC and
      genotype. CONCLUSIONS: The SNPs selected for this study do not appear to modify
      disease expression in HNPCC. Given the complexity of the inflammatory response,
      the limited number of SNPs studied does not rule out the notion that other
      cytokine polymorphisms could act as disease modifiers of disease expression in
      HNPCC.

PMID- 17454885
TI  - Gastric GIST malignancy evaluated by 18FDG-PET as compared with EUS-FNA and
      endoscopic biopsy.
AB  - OBJECTIVE: The usefulness of 18F-fluoro-2-deoxyglucose positron emission
      tomography (18FDG-PET), whose high rate of FDG accumulation indicates high
      metabolism and malignant potential, has already been reported. The aims of this
      study were to evaluate the malignancy of primary gastrointestinal stromal tumour
      (GIST) in the stomach by 18FDG-PET and to correlate the FDG uptake values with
      known risk factors as determined by histology after EUS-guided fine needle
      aspiration (EUS-FNA) or endoscopic biopsy. MATERIAL AND METHODS: Of 29 patients
      with histologically proven GI-mesenchymal tumours, 21 with gastric GISTs
      underwent 18FDG-PET. Tumour size, mitotic index, Ki-67 labelling index (LI) and
      cellularity of the tumour tissue were compared with the standardized uptake value
      (SUV) of FDG. RESULTS: Strong correlations were found between the SUV of FDG and
      EUS size, and mitotic index of EUS-FNA specimens (tumour size versus SUV,
      p=0.004, r=0.542; number of mitotic cells versus SUV, p=0.0078; n=21). Moreover,
      we examined the association between SUV and risk categories based on EUS-FNA
      findings using ROC curves. The cut-off values of FDG SUV were 2.2, 4.2 and 6.5
      for the very low-, low-, intermediate- and high-risk groups, respectively.
      CONCLUSIONS: 18FDG-PET may be used to assess malignancy of GISTs. This image
      modality helps us determine the management strategy for these patients and
      complements the information on the biological behaviour and cellular
      proliferation of the tumours.

PMID- 17454886
TI  - Daily profile of circulating C-type natriuretic peptide in pre-ascitic cirrhosis
      and in normal subjects: relationship with renal function.
AB  - OBJECTIVE: To investigate whether the C-type natriuretic peptide (CNP) has a role
      in the regulation of fluid and sodium homeostasis in normal subjects and in pre
      ascitic cirrhotic patients. MATERIAL AND METHODS: The daily profile of CNP plasma
      levels was assessed by serial measurements (0700 h, 0900 h, 1800 h, 2300 h) in 10
      pre-ascitic cirrhotic outpatients (age 56+/-4 years) and in 10 age-matched
      healthy controls (54+/-2 years) on a normal sodium diet (150 mmol/day) while
      carrying on their usual activities (mobile from 0700 h to 2200 h), after an
      equilibration period of 5 days. Daily diuresis and natriuresis were also
      monitored. RESULTS: Mean daily CNP was comparable in cirrhotic and healthy
      subjects (3.64+/-0.32 versus 3.20+/-0.20 pg/ml; p=0.139); CNP concentration
      showed a tendency towards a circadian fluctuation in healthy subjects (p=0.053)
      but not in patients (p=0.171). Mean daily CNP concentration significantly
      correlated with 24-h natriuresis (r=0.709; p=0.022) and urine volume (r=0.745;
      p=0.013) in patients but not in healthy subjects. CONCLUSIONS: CNP plasma levels
      appear to play a role in the water-sodium balance regulation in patients with pre
      ascitic cirrhosis.

PMID- 17454887
TI  - Surgery for acute cholecystitis in Denmark.
AB  - OBJECTIVE: Despite laparoscopic cholecystectomy being the preferred treatment for
      elective cholecystectomy, surgery for acute cholecystitis is often performed
      using the open method. The aim of the study was to assess the incidence of
      cholecystectomy for acute cholecystitis and to determine the proportion of
      laparoscopically completed procedures compared with all cholecystectomies for
      acute cholecystitis. MATERIAL AND METHODS: Data from the Danish National Patient
      Registry were analysed. The annual numbers of all cholecystectomies and of
      cholecystectomies performed for acute cholecystitis from 1996 to 2004 were
      registered. Separate data for open and laparoscopic operations were obtained.
      RESULTS: An increase in the number of cholecystectomies for acute cholecystitis
      from 13.6 in 1996 to 17.2/100,000 in 2004 was observed (p<0.05). In 1996, 41% of
      cholecystectomies performed for acute cholecystitis were completed
      laparoscopically as compared with 64% in 2004 (p<0.05). For laparoscopic
      cholecystectomies performed for reasons other than acute cholecystitis, the
      corresponding rates were 78% and 87%, respectively (p<0.05). CONCLUSIONS: The
      total number of patients having cholecystectomy for acute cholecystitis has
      increased as has the rate of laparoscopically completed procedures. It is not
      known whether it is possible to obtain a further reduction in the number of open
      cholecystectomies.

PMID- 17454888
TI  - Analysis of neuroendocrine tumour metastases in the liver using contrast enhanced
      ultrasonography.
AB  - BACKGROUND: Imaging of liver tumours might be improved by contrast-enhanced
      ultrasonography, which allows much better demonstration of the microvascular
      system. The aim of this study was to assess the sonographic morphology and
      vascularity of neuroendocrine liver metastases. METHODS: Forty-eight patients
      with histologically proven neuroendocrine tumours (NET) and suspected liver
      metastases--as well as 50 consecutive patients with liver metastases of other
      origins--were included in a prospective study to evaluate tumour characteristics
      using B-mode, colour Doppler (CDI) and contrast-enhanced ultrasound (CEUS).
      RESULTS: In 4/48 patients with NET, liver biopsy revealed hemangiomas. The
      typical B-mode appearance was that of both echo-rich and echo-poor combined, also
      inhomogeneous depending on the size, and often centrally cystic. With CDI,
      neuroendocrine metastases appeared hypervascular (66%) or isovascular (34%).
      Metastases of another origin were hypovascular in 82%. With CEUS, neuroendocrine
      metastases showed increased arterial enhancement in 38 patients and hypoechoic
      appearance in the portalvenous phase in 39 patients. In liver metastases of
      another origin, the sensitivity for malignancy due to a hypoechoic appearance
      during the portalvenous phase was 100%. In liver metastases of NET origin the
      sensitivity for malignancy was 39/48 (82%). CONCLUSIONS: Neuroendocrine tumour
      metastases might show characteristics which are similar to hemangiomas. In
      patients with liver cirrhosis and severe fatty liver disease the identification
      of NET with CEUS as a malignant lesion is more difficult. The sensitivity of CEUS
      in identifying malignancy based on the lack of portalvenous enhancement is higher
      for metastases of other origin.

PMID- 17454889
TI  - The German physician Walter Krienitz: a pioneer in gastric research.

PMID- 17454890
TI  - Terlipressin causing a hyponatraemic seizure.

PMID- 17454891
TI  - Antibiotic susceptibility, serotype distribution and vaccine coverage of
      nasopharyngeal and oropharyngeal Streptococcus pneumoniae in a day-care centre in
      St. Petersburg, Russia.
AB  - The objectives were to study serotypes and antibiotic susceptibility of
      Streptococcus pneumoniae carried by healthy children attending a day-care centre
      in St. Petersburg. S. pneumoniae colonization was investigated in 125 children
      aged 16-70 months. Antibiotic susceptibility was determined by E-test and disk
      diffusion. 83 S. pneumoniae cases were isolated in 75/125 (60%) children: 36/75
      (48%) in the nasopharynx, 12/75 (16%) in the oropharynx and 27/75 (36%) in both.
      Carriage rates were 100%, 68%, 72%, 46% and 54% in children aged 12-23, 24-35, 36
      47, 48-59 and >or=60 months, respectively. 97.6% of isolates were susceptible to
      penicillin. 61.4%, 32.5%, 19.3%, 16.7% and 6% isolates were non-susceptible to
      trimethoprim/sulfamethoxazole, tetracycline, clindamycin, erythromycin and
      chloramphenicol, respectively. 20.5% of isolates were multidrug resistant (MDR).
      45% of isolates were of serotypes included in the 7-valent pneumococcal conjugate
      vaccine (7V-PCV); 64.9%, 56.8%, 32.4% and 27% of 7V-PCV serotypes were resistant
      to trimethoprim/sulfamethoxazole, tetracycline, clindamycin and erythromycin,
      respectively. The respective figures for MDR isolates were 100%, 94.1%, 70.6% and
      76.5%; 76.5% of all MDR isolates were covered by 7V-PCV. IN CONCLUSION: 1)
      resistance to trimethoprim/sulfamethoxazole and tetracycline was high; 2)
      resistance to macrolides was higher than in other Russian regions; 3) 7V-PCV
      coverage was modest, but the vaccine may potentially reduce MDR-S. pneumoniae.

PMID- 17454892
TI  - Infective endocarditis due to community-associated methicillin-resistant
      Staphylococcus aureus in injection drug users may be associated with Panton
      Valentine leukocidin-negative strains.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
      isolates that cause infective endocarditis in injection drug users (IDUs) are
      distinct from CA-MRSA strains that cause endocardial infection as a complication
      of skin and soft tissue infections. We present a case of CA-MRSA infective
      endocarditis, review pertinent cases previously published, and describe the
      molecular characteristics of strains from IDUs and patients with skin and soft
      tissue infections.

PMID- 17454893
TI  - Serum anti-Helicobacter pylori IgA and IgG antibodies in asymptomatic children in
      Serbia.
AB  - The aim of this study was to determine the seroprevalence of Helicobacter pylori
      and the distribution of anti-H.pylori IgA and IgG antibodies in asymptomatic
      children aged between 7 and 18 y. We studied the serum samples of 283 children
      using the commercial ELISA test for the detection of anti-H. pylori IgA and IgG
      antibodies. The overall prevalence of anti-H. pylori antibodies was 36.4%. The
      seroprevalence was 35%, 28.3%, 37.5%, and 42.2% for the ages of 7, 10, 14 and 18
      y, respectively. Serum IgG antibodies alone were detected in 88.3%, IgA alone in
      4.9%, and both IgA and IgG antibodies were detected in 6.8% of samples. The mean
      levels of IgG antibodies to H. pylori increased with age. We concluded that the
      prevalence of H. pylori antibodies in Serbian children was high (36.4%), ranging
      from 35% to 42.2%. The detection of IgG antibodies is useful for the
      determination of seroprevalence in asymptomatic children.

PMID- 17454894
TI  - Tuberculosis in St. Petersburg and the Baltic Sea region.
AB  - Tuberculosis (TB) remains a global public health concern and challenges the
      national structures for infection control and health care, as well as
      international institutions, to develop and implement new strategies to control
      and combat this disease. In our report, we investigated the TB epidemiological
      situation in St. Petersburg and the countries around the Baltic Sea using
      national epidemiological statistics and epidemiological reports of international
      organizations, such as the WHO and Euro-TB. After the disintegration of the
      Soviet Union, a steep increase in tuberculosis was seen in the Russian
      Federation, St. Petersburg and the Baltic States, after which it stabilized at
      levels significantly higher compared to the Nordic countries. Moreover, the
      epidemiological situation in St. Petersburg and the Baltic States was aggravated
      by the emergence and spread of TB/HIV coinfection, as well as that of drug
      resistant M. tuberculosis, which imposed further difficulties in gaining control
      of TB. During the studied period, the TB burden in neither St. Petersburg nor
      Baltic States has had a significant impact on the epidemiology in the low TB
      burden neighbouring countries around the Baltic Sea.

PMID- 17454895
TI  - LPS-based conjugate vaccines composed of saccharide antigens of smooth-type
      Salmonella enteritidis and rough-type S. gallinarum 9R bound to bovine serum
      albumin.
AB  - Lipopolysaccahrides (LPSs) from Salmonella enteritidis, S. gallinarum, and S.
      enterica Typhimurium showed an identical electrophoretic banding pattern and
      serological cross-reactions among each other. LPSs from wild-type Salmonella
      enteritidis and rough mutant S. gallinarum 9R were detoxified by cleavage of
      lipid A moieties using mild acid hydrolysis. The non-toxic saccharide moieties
      from both strains were coupled directly to bovine serum albumin (BSA). The
      conjugates were injected in mice in combination with monophosphory lipid A (MPL),
      Freund, and Alum adjuvants. The highest IgM and IgG titres were obtained when the
      conjugates were emulsified with MPL adjuvant, followed by Freund adjuvant. The
      antisera raised against the conjugates in combination with MPL and Freund
      adjuvants showed high complement-mediated lysis to the homologous strains. A
      correlation was observed between IgG titres and bactericidal activities against
      homologous strains. Low in vivo protection was obtained when mice immunized with
      the conjugates were challenged with 10 times the LD50 of the wild S. enteritidis.

PMID- 17454896
TI  - Outbreak of norovirus in Vastra Gotaland associated with recreational activities
      at two lakes during August 2004.
AB  - A large community outbreak of norovirus (NV) gastrointestinal infection occurred
      in Vastra Gotaland County, Sweden in August 2004, following attendance at
      recreational lakes. A frequency age-matched case control study was undertaken of
      persons who had attended these lakes to identify risk factors. 163 cases and 329
      controls were included. Analysis indicates that having water in the mouth while
      swimming (OR=4.7; 95% CI 1.1-20.2), attendance at the main swimming area at
      Delsjon Lake (OR=25.5; 95% CI 2.5-263.8), taking water home from a fresh water
      spring near Delsjon lake (OR=17.3; 95% CI 2.7-110.7) and swimming less than 20 m
      from shore (OR=13.4; 95% CI 2.0-90.2) were significant risk factors. The probable
      vehicle was local contamination of the lake water (especially at the main
      swimming area). The source of contamination could not be determined.

PMID- 17454897
TI  - Crimean-Congo haemorrhagic fever cases in Turkey.
AB  - Crimean-Congo haemorrhagic fever (CCHF) is an arbovirus infection, which is
      transmitted through ticks or via blood and secretions. Until recently, human
      cases of CCHF were unknown in Turkey; however, several acute disease cases were
      reported in 2002. We report on the investigation of a cluster of suspected CCHF
      cases in the middle part of the Black Sea from May 2002 to October 2003. The
      medical charts that we reviewed were obtained from all local physicians and our
      field investigations. 'Suspected case' was defined with regard to time, place,
      and both clinical and laboratory characteristics. A total of 108 patients were
      defined as suspected case. Among them 36 patients were reached and blood samples
      taken for examination for CCHF by using ELISA and RT-PCR. According to the
      laboratory analysis, 80.6% (29/36) were acute cases and 8.3% (3/36) were past
      CCHF infections. The overall mortality rate was 5.6%. There was no nosocomial
      infection; however, there were 2 family clusters. Tick exposure was the most
      prevalent risk factor (74.2%). A multidisciplinary collaboration should be
      developed in order to understand the magnitude of the disease and also to keep it
      under control.

PMID- 17454898
TI  - Diagnostics of fungal infections in the Nordic countries: we still need to
      improve!
AB  - A Nordic External Quality Assessment programme in medical mycology was
      established in 2005. In order to monitor not 'best practice' but the level of
      routine diagnostics, specimens were designed to resemble clinical samples and
      laboratories were asked to handle the samples like routine samples. Five
      simulated clinical samples were distributed to 59 participating Nordic
      laboratories of clinical microbiology. The specimens contained the following
      microorganisms: 1) Candida glabrata and C. albicans in a ratio of 1:20; 2)
      Cryptococcus neoformans; 3) Aspergillus fumigatus, C. albicans and Enterobacter
      cloacae; 4) C. tropicalis, Klebsiella pneumonia and Enterococcus faecium; 5)
      None. 66% of the laboratories failed to detect the C. glabrata isolate in sample
      no. 1. 34% of the laboratories reporting susceptibility results incorrectly
      reported the Cryptococcus neoformans isolate as fluconazole susceptible. 24% of
      the laboratories failed to detect Aspergillus fumigatus in specimen no. 3 despite
      the accompanying clinical information notifying that it was a BAL sample from a
      neutropenic patient in an ICU. In conclusion, this distribution of simulated
      clinical samples illustrates that the traditional quality assessment programmes
      may give a false sense of satisfactory performance, that mycological diagnosis is
      difficult, and that there is a need of further improvement and attention.

PMID- 17454899
TI  - A case of invasive central nervous system aspergillosis treated with micafungin
      with monitoring of micafungin concentrations in the cerebrospinal fluid.
AB  - Invasive aspergillosis has an extremely high mortality rate. In Japan,
      micafungin, an echinocandin drug that has a new mechanism of action as an
      antifungal agent and has a clinical effect against Aspergillus species, became
      available in 2002. However, little is known about its penetration into the
      central nervous system (CNS), or its efficacy for the treatment of invasive CNS
      aspergillosis. We report a 65-y-old female with diabetes mellitus and CNS
      aspergillosis who was treated with micafungin. During treatment, micafungin
      concentrations were measured in the cerebrospinal fluid and plasma. On a dose of
      300 mg/d, the ratio of the micafungin concentration in the cerebrospinal fluid to
      that in plasma was extremely low (0.2%-0.05%); nevertheless, the patient did not
      have a relapse of invasive CNS aspergillosis after micafungin treatment.

PMID- 17454900
TI  - Immune reconstitution after potent antiretroviral therapy in AIDS patients with
      progressive multifocal leukoencephalopathy.
AB  - Neurological disease is the initial manifestation of acquired immunodeficiency
      syndrome (AIDS) in 10-20% of patients with HIV infection. Progressive multifocal
      leukoencephalopathy (PML) predominantly involves the cerebral hemispheres, with a
      small subset of patients having lesions predominantly or exclusively confined to
      the cerebellum. The radiological features of PML are typically non-inflammatory.
      As a result of potent antiretroviral therapy (ART), however, inflammatory lesions
      are becoming more common in HIV-infected individuals and are due, in part, to
      immune reconstitution that occurs in recipients of potent ART. In the majority of
      such cases, the clinical outcome of immune reconstitution PML has been beneficial
      to the host, although several case reports have described worsening or fatal
      outcomes in PML patients as a result of potent ART. The following 2 cases of
      immune reconstitution PML described in this report illustrate the varied
      radiological manifestations and clinical outcomes that can develop in AIDS
      patients with PML receiving potent ART. Moreover, these cases highlight the
      inflammatory changes observed on neuroimaging in AIDS patients with immune
      reconstitution PML receiving potent ART and to our knowledge are the first
      reports of immune reconstitution isolated to the cerebellum in such patients.

PMID- 17454901
TI  - Simultaneously acute hepatitis B virus and C virus coinfection and subsequent
      chronic hepatitis C.
AB  - Hepatitis C virus (HCV) and hepatitis B virus (HBV) share similar transmission
      routes, but concurrent acute HCV and HBV infection was rarely reported. Little is
      known about viral interaction and hepatic biochemical features of acute HBV and
      HCV coinfection. We report an intravenous drug abuser with simultaneous acute HBV
      and HCV infections presenting as biphasic elevation of both alanine
      aminotransferase (ALT) and total bilirubin levels. HCV infection is the major
      cause of continuing hepatitis after termination of HBsAg antigenemia.

PMID- 17454902
TI  - Post partum osteomyelitis due to Cryptococcus neoformans.
AB  - We report a case of Cryptococcus neoformans in a pregnant woman whose initially
      mild symptoms of infection deteriorated after delivery. This is the first
      reported case of C. neoformans osteomyelitis in pregnancy.

PMID- 17454903
TI  - Melioidosis complicated by pericarditis.
AB  - Melioidosis is a bacterial infection caused by the Gram-negative bacillus
      Burkholderia pseudomallei. We report an unusual case of melioidosis that
      presented as a pyrexia of unknown origin complicated by pericardial effusion. Our
      patient received a 6-week course of intravenous antibiotics, followed by 8 months
      of oral antibiotics, and made a complete recovery. This report illustrates the
      diagnostic and therapeutic challenge that clinicians may encounter when faced
      with this potentially fatal infection.

PMID- 17454904
TI  - Shewanella spp. infection following treatment for upper gastrointestinal
      bleeding.
AB  - Shewanella spp. are an uncommon cause of human infection, with exposure to water
      being the commonest source. We report a patient with a malignancy and upper
      gastrointestinal bleeding who underwent a gastric lavage followed by an endoscopy
      as part of her investigations. She subsequently developed Shewanella spp.
      bacteraemia without any clinical source of infection.

PMID- 17454905
TI  - Common variable immune deficiency and lung transplantation.
AB  - We report on a male patient with bronchiectasis secondary to common variable
      immune deficiency (CVID) receiving lung transplantation. The patient had been
      diagnosed with CVID many y prior to right-sided single lung transplantation and
      was receiving appropriate immunoglobulin substitution therapy. He received
      antithymocyte globulin induction and maintenance triple therapy with
      cyclosporine, azathioprine and prednisolone. The early post-operative course was
      complicated by the development of severe acute cellular rejection and organizing
      pneumonia. Despite immunoglobulin replacement and antifungal prophylaxis and
      treatment, Aspergillus fumigatus was repeatedly cultured from bronchoalveolar
      lavage fluid, 18 months after transplantation. The patient died following a
      protracted period of repeated hospital admissions, 46 months after
      transplantation. A review of the literature suggests that many CVID patients
      appear to have had a complicated post-operative course after lung- and other
      solid-organ transplantation, and highlights the need for the establishment of
      international registries for transplanted patients with uncommon conditions.

PMID- 17454906
TI  - Knee septic arthritis due to Streptococcus pyogenes associated with acute
      thrombosis of the tibial and peroneal veins: case report and review of the
      literature.
AB  - We present the case of a 53-y-old patient who complained of fever, pain and
      oedema of the right knee and the right calf. Colour ultrasonography showed
      thrombosis of the tibial and peroneal veins, while paracentesis of the knee joint
      showed characteristics of an inflammatory exudate. Culture of the arthritic fluid
      revealed Streptococcus pyogenes. Thus, a diagnosis of a septic arthritis of the
      right knee in association with deep venous thrombosis of the right lower leg was
      established. From a review of the literature we found no other cases of septic
      arthritis in association with thrombosis of the adjacent vein. In conclusion, in
      cases of septic arthritis of a joint one has to consider ruling out thrombosis of
      the adjacent venous vessels, especially when oedema is not confined to the joint.
      Missing the diagnosis of such a complication will lead to increased morbidity and
      mortality.

PMID- 17454907
TI  - A case of malignant otitis externa caused by Candida glabrata in a patient
      receiving haemodialysis.
AB  - A 74-y-old male receiving haemodialysis presented with right-sided otalgia,
      otorrhoea and diffuse swelling on the right external auditory canal. Following an
      initial successful treatment with prolonged intravenous antibiotics, the patient
      relapsed with a secondary infection in the same site due to Candida glabrata. We
      report an unusual case of malignant otitis externa caused by the fungus C.
      glabrata.

PMID- 17454908
TI  - Proteus mirabilis: a rare cause of infectious endocarditis.
AB  - Native valve endocarditis resulting from Proteus mirabilis is an exceptionally
      rare entity. To date, 10 cases have been reported. We present a case of a 58-y
      old female with fevers, bacteremia, and embolic phenomenon. Unlike previous
      cases, early antibiotic treatment precluded valvular repair or death, leading to
      a favorable outcome.

PMID- 17454909
TI  - Stenotrophomonas maltophilia infection of the central venous catheter and lysis
      of an old thrombosis in a post-bone marrow transplantation child: implications in
      the fibrinolytic process.
AB  - In this report, we describe an 11-y-old girl who developed jugular venous
      thrombosis after allogeneic bone marrow transplantation for lymphoma and then
      experienced dissolution of the thrombosis following catheter-related
      Stenothrophomonas maltophilia bactearemia. The lysis of the old thrombosis around
      the central venous catheter suggested a local fibrinolytic activity of S.
      maltophilia. The global fibrinolytic capacity (GFC) was also tested in vitro by
      using S. maltophilia cultures obtained from the present patient; GFC of the
      patient was compared to that of another isolate of S. maltophilia, other bacteria
      (S. pyogenes and E. coli), and control plasma. The fibrinolytic capasity of S.
      maltophilia was significantly higher than that of the control plasma (p<0.05) and
      almost equal to that of S. pyogenes (p>0.05). Thus, if a potent local
      fibrinolytic activity of S. maltophilia is evident, the use of the fibrinolytic
      enzyme of S. maltophilia as a thrombolytic agent may be a useful therapeutic
      adjunct in the future. Further studies are needed to comfirm the results obtained
      in the present study.

PMID- 17454910
TI  - Splenic abscess due to Brucella infection: is the splenectomy necessary? Case
      report and literature review.
AB  - The case of a woman with splenic abscess due to Brucella is reported. There was
      no response with antibiotics and surgical treatment was required. On the basis of
      this case and the literature review we consider that surgical treatment must be
      considered in patients with splenic abscess due to Brucella infection.

PMID- 17454911
TI  - Leptotrichia amnionii found in septic abortion in Denmark.
AB  - Leptotrichia amnionii was first described in 2002 in the USA. Only few cases have
      been reported to date, 3 in pregnant women and 2 in non-pregnant women. We
      present the first case of L. amnionii in Scandinavia, found in a woman with
      spontaneous second trimester septic abortion.

PMID- 17454912
TI  - Culture negative endocarditis: analysis of 201 cases.

PMID- 17454913
TI  - Health inequalities across the globe demand new global policies.

PMID- 17454914
TI  - Privacy in occupational health practice: promoting and impeding factors.
AB  - AIM: This article describes the views of occupational health professionals,
      employees, and employers on factors that are thought to promote and impede
      privacy in occupational health practice. METHODS: The data were collected through
      theme interviews with 44 subjects and were analysed by content analysis. RESULTS:
      Both promoting and impeding factors organized around two content areas:
      "caregiving" (patient-caregiver relationship) and "tripartite cooperation"
      (cooperation between occupational health professionals, employees, and employer).
      The content areas illustrated the two different roles Finnish occupational health
      professionals have toward their two groups of clients: employees and employers.
      "Adequate behaviour" (respect, good communication, presence) and "Adequate
      knowledge base" (instinct, work experience, ethical thinking, knowledge of
      legislation) promoted privacy in caring relationship, whereas "Inadequate
      behaviour" (untrustworthy, busy, distant, "friend") impeded its realization. In
      tripartite cooperation, the promoting factors had to do with "Common good"
      (impartiality, regular contacts, community spirit, fair play) and "Individual
      good" (informed consent, advocacy). The main category, "Confusions in loyalties",
      emerged from three subcategories (confusions in confidentiality, confusions in
      duties, and confusions in roles) illustrating the impeding factors in tripartite
      cooperation. CONCLUSIONS: Questions of privacy are crystallized in occupational
      health professionals' diverse duties and roles towards employees and employers.
      In occupational health practice, privacy cannot be seen only as a privilege of
      employees, but must also be viewed as an instrumental value serving the interests
      of employers and whole work community. Confusions in loyalties need more
      discussion and research before privacy can be optimally realized. Lapses in
      confidentiality should never happen.

PMID- 17454915
TI  - How valid are parents' questionnaire responses regarding building
      characteristics, mouldy odour, and signs of moisture problems in Swedish homes?
AB  - AIM: Questionnaires are a cheap means of studying large populations but the
      information obtained from them is seldom validated. Earlier studies have reported
      both high and low levels of agreements between inspectors' observations and
      occupants' reports regarding home environmental factors that included moisture
      problems. The aim of this study was to validate information received from a
      questionnaire survey regarding building characteristics, mouldy odour, and signs
      of moisture problems in 390 Swedish homes. METHOD: In a case control study on the
      association between home environmental factors and asthma/allergy among children,
      390 homes were visited by trained inspectors for ocular inspection of visible
      moisture damage and perceptions of mouldy odour. Their observations were then
      compared with questionnaire reports collected 18-24 months earlier from the
      families. RESULTS: A high level of agreement was found between the inspectors'
      observations and the occupants' questionnaire reports on technical parameters.
      This included type of house, type of ventilation system, and foundation,
      particularly in single-family houses. There was low agreement regarding vinyl or
      linoleum floor coverings and indications of dampness and mouldy odour. However,
      the stronger the mouldy odour experienced by the inspector, the higher the level
      of agreement. CONCLUSIONS: The questionnaire was a quite reliable source
      regarding technical parameters of the home but not for dampness problems. The
      questionnaire was better for predicting buildings without problems than detecting
      problems of mouldy odour and visible indications of moisture. To increase the
      validity of future questionnaires, simple drawings or information on critical
      spots for dampness could be used.

PMID- 17454916
TI  - Sex-specific suicide mortality in the South African urban context: the role of
      age, race, and geographical location.
AB  - AIMS: This study investigates the importance of sociodemographic and geographical
      characteristics for suicide risks in the South African urban context. Suicide
      epidemiology is under-researched in low- and middle-income countries, and such
      knowledge is important not only for local and national policy, but also for a
      global understanding of the phenomenon. METHODS: Sex-specific crude and adjusted
      odds ratios (95% confidence intervals) for suicide by age, race, and city are
      assessed using logistic regression. Cases aged 45+ years, classified as
      "Coloured" (a category denoting mixed racial origin), and living in Cape Town are
      used as reference groups. Additionally, the proportion of leading suicide methods
      within groups was estimated (95% confidence intervals). RESULTS: For males,
      compared with each reference group, the odds of suicide are significantly higher
      during middle adulthood, among Asians and particularly among Whites, and among
      residents of all but one city. Patterns for women differ in magnitude and
      distribution. Suicide odds are significantly higher in all age groups,
      particularly 15-24 years, among Whites, and among residents of all other cities,
      particularly Nelson Mandela or Buffalo City. Males living in Tshwane and Black
      females have lower odds of suicide. The distribution of methods across age, race,
      and city groups varies little for males but substantially for females.
      CONCLUSIONS: Age, race, and city play independent roles in sex-specific suicide
      rates. As for high-income settings, age, race, method and city are important in
      sex-specific suicide in the urban South African context. Possible underlying
      mechanisms deserve greater attention for context-relevant preventive efforts.

PMID- 17454917
TI  - Examining the "Matthew Effect" on the motivation and ability to make lifestyle
      changes in 217 heart rehabilitation patients.
AB  - AIMS: Those who are socioeconomically disadvantaged and people with emotional
      problems have a poorer prognosis for cardiovascular disease. The authors wanted
      to examine: (1) what effect household income, emotional status, high-risk smoking
      status, and severity of heart disease had on the ability of individuals to make
      dietary and exercise improvements after heart disease and (2) to what extent
      unfavourable lifestyle outcomes among disadvantaged people were mediated by
      motivational problems. METHODS: A two-year follow-up study of the combined
      cohorts of a randomized controlled trial. Level of exercise and present dietary
      habits were measured at inclusion and after 6 and 24 months. Different
      motivational factors and emotional distress were measured during rehabilitation.
      RESULTS: Autonomous self-regulation was lowest among smokers (b = -0.31, p =
      0.02) and female participants (b = 0.39, p = 0.004). Participants with high
      scores of emotional distress predicted lower motivation for all the measures. We
      found no association between socioeconomic status (household income) and the
      ability to perform lifestyle changes. Current smoking status predicted lower
      ability to obtain lifestyle changes on all measures. Emotional distress was
      related to lower ability to increase physical activity at 6 months' but not at 24
      months' follow-up. The mediating effects of motivational factors were
      insignificant. CONCLUSIONS: The results of this study do not support the
      suspicion that preventive efforts accentuate the socioeconomic differences in
      cardiovascular health. Health-promotive efforts after heart disease should
      safeguard that high-risk groups such as smokers are not discouraged from
      improving their lifestyle in other areas.

PMID- 17454918
TI  - Perceptions of potential donors in the Swedish public towards information and
      consent procedures in relation to use of human tissue samples in biobanks: a
      population-based study.
AB  - AIMS: To assess the Swedish public's preferences for information and consent
      procedures when being asked for permission to use previously collected tissue
      samples for new research studies. METHODS: Cross-sectional study employing postal
      questionnaires to a random sample of the Swedish general public (n = 6,000) in
      October 2002-February 2003. The response rate was 49% (n = 2,928). This paper
      includes only respondents who reportedly would approve of samples being taken and
      stored (n = 2,122). RESULTS: When potential tissue sample donors in the general
      public have to strike a balance between the values at stake, i.e. the autonomy of
      the donor versus the research value, most (72%) prefer general consent, i.e.
      where consent is asked for at the outset only. They want the research ethics
      committee (REC) alone to decide on the use of stored samples, and they would
      allow storage as long as the sample is useful for research. The minority of
      respondents who were in favour of specific consent were more likely to be young,
      well educated, have negative experiences of healthcare and low trust in
      healthcare authorities. CONCLUSIONS: The majority of the Swedish general public
      prefer general consent, and are thus willing to delegate some decisions to the
      RECs. However, preferences for information and consent procedures depend on the
      context, e.g. the risks for the donor and the purpose of the research. If
      feasible, procedures should be differentiated according to the preferences of
      individual donors, thus protecting the interests of both the minority and the
      majority.

PMID- 17454919
TI  - Does mastering have an effect on disability pensioning independent of health, and
      may it explain divides of education in the Oslo Health Survey?
AB  - AIMS: Does mastering abilities have an independent effect on disability
      pensioning? Are some of the large divides across education explained by mastering
      factors when adjusted for health? METHODS: Data from the National Insurance
      Administration were linked to a health survey of 10,720 Oslo inhabitants aged 40,
      45, and 60 years, 46% of the total populations in these age groups who were
      invited to a Health Survey in 2000-01. Measures of general health, chronic
      somatic diseases, psychiatric symptoms, and musculoskeletal pain were self
      reported. The mastering test Generalized Self Efficacy was used. RESULTS: 10.5%
      of our eligible sample had disability pension at the time of the survey. The risk
      was more than five times higher for those with primary school than for those with
      university education and 50% higher for women than for men. Lowest score on the
      Generalized Self Efficacy test (poor mastering) had an age-, gender-, and health
      adjusted OR of 2.4 compared with the highest level of mastering. Adjusting for
      mastering lowered the educational divide but not that of gender, when health
      indicators were taken into consideration Those reporting poor general health had
      a seven times higher risk than those with good health, and those with a chronic
      somatic disease, musculoskeletal pain, or poor psychiatric health had a somewhat
      lower increase in risk of disability pension. Health measures did reduce the
      impact of education, but not of gender, when adjusted for mastering. CONCLUSION:
      Poor mastering was associated with disability pensioning, and reduced the
      differences across educational level and health but not across gender.

PMID- 17454920
TI  - Self-rated health and age: a cross-sectional and longitudinal study of 11,000
      Danes aged 45-102.
AB  - AIMS: The aim of this study was to explore and describe self-rated health in
      middle-aged and elderly Danes using both a cross-sectional and a longitudinal
      design. Global and (age) comparative self-rated health are examined and compared.
      METHODS: This study is interview based and comprises data on 11,294 Danes aged 45
      102 with more than 1,900 participants aged 90 years and older. RESULTS: As
      expected, global self-rated health declines with age in both cross-sectional and
      longitudinal analyses. In contrast, comparative self-rated health either
      increases or remains stable with age in cross-sectional analyses while in
      longitudinal analyses there is a slight decline in comparative self-rated health.
      CONCLUSIONS: The age-trajectory of global self-rated health is similar in
      individuals and populations. For comparative self-rated health, however, the
      individual on average experiences a slight decline, whereas on the population
      level comparative self-rated health either increases or remains stable. The
      explanation for this is likely to be higher mortality and higher non-response
      among the participants with the poorest self-rated health.

PMID- 17454921
TI  - Relative validity of fruit and vegetable intake estimated by the food frequency
      questionnaire used in the Danish National Birth Cohort.
AB  - OBJECTIVE: To validate the fruit and vegetable intake estimated from the Food
      Frequency Questionnaire (FFQ) used in the Danish National Birth Cohort (DNBC).
      SUBJECTS AND SETTING: The DNBC is a cohort of 101,042 pregnant women in Denmark,
      who received a FFQ by mail in gestation week 25. A validation study with 88
      participants was made. A seven-day weighed food diary (FD) and three different
      biomarkers were employed as comparison methods. RESULTS: Significant correlations
      between FFQ and FD-based estimates were found for fruit (r = 0.66); vegetables (r
      = 0.32); juice (r = 0.52); fruit and vegetables (F&V) (r = 0.57); and fruit,
      vegetables, and juice (F&V&J) (r = 0.62). Sensitivities of correct classification
      by FFQ into the two lowest and the two highest quintiles of F&V&J intake were 58
      67% and 50-74%, respectively, and specificities were 71-79% and 65-83%,
      respectively. F&V&J intake estimated from the FFQ correlated significantly with
      urinary flavonoids (r = 0.39, p<0.005), plasma beta-carotene (r = 0.21, p<0.05)
      and erythrocyte folate (r = 0.33, p<0.005); all average biomarker levels
      increased across increasing quintiles of F&V&J intake. CONCLUSION: Data on F&V&J
      recorded by FFQ in DNBC can be used in etiological analyses of associations
      between fruit and vegetable intake and health outcomes, provided that the
      potential misclassification of dietary exposure is kept in mind.

PMID- 17454922
TI  - Escaping the triple trap: coping strategies of pregnant adolescent survivors of
      domestic violence in Mulago hospital, Uganda.
AB  - OBJECTIVE: Why domestic violence survivors develop adverse outcomes following
      domestic violence during pregnancy is unclear, but may depend on how survivors
      cope with the stress of violence. The objective was to describe strategies
      pregnant adolescents employ in coping with domestic violence. METHODS: This was a
      qualitative study involving 16 in-depth interviews with adolescent domestic
      violence survivors who attended the antenatal clinic in Mulago hospital, Kampala,
      Uganda, from January to May 2004. Theoretical sampling, necessitated by the
      emergent theory from sequential data collection and analysis, further provided
      diversity of experiences from adolescents of different ages, parity, pregnancy
      duration, and socioeconomic status until saturation was reached. Data were
      analyzed using grounded theory. FINDINGS: Survivors described varied experiences
      of physical, sexual, and psychological violence. Coping strategies employed were
      analyzed as: Minimizing damage - decreasing impact and severity of violence,
      withdrawal - physical or social withdrawal, seeking help and retaliation
      (fighting back). Coping strategies were influenced by adolescence and pregnancy,
      and are explained in relation to theories of coping with stress. CONCLUSIONS:
      Coping strategies adopted by pregnant adolescent survivors range from problem
      focused approaches to emotion-focused approaches. Coping strategies are
      influenced markedly by adolescence and pregnancy.

PMID- 17454923
TI  - Smoking, healthcare cost, and loss of productivity in Sweden 2001.
AB  - AIMS: Objectives were (a) to estimate healthcare cost and productivity losses due
      to smoking in Sweden 2001 and (b) to compare the results with studies for Sweden
      1980, Canada 1991, Germany 1996, and the USA 1998. METHODS: Published estimates
      on relative risks and Swedish smoking patterns were used to calculate
      attributable risks for smokers and former smokers. These were applied to cost
      estimates for smoking-related diseases based on data from public Swedish
      registers. RESULTS: The estimated total cost for Sweden 2001 was US 804 million
      dollars; COPD and cancer of the lung accounted for 43%. Healthcare cost accounted
      for 26% of the total cost. The estimated costs per smoker were US 3,200 dollars
      in the USA 1998; 1,600 in Canada 1991; 1,100 in Germany 1996; 600 in Sweden 2001;
      and 300 in Sweden 1980 (all in 2001 US dollar prices). CONCLUSIONS: To reduce the
      prevalence of smoking is an issue worthwhile pursuing in its own right. In order
      to reduce the cost of smoking, however, policy-makers should also explore and
      influence the factors that determine the cost per smoker. Sweden seems to have
      been more successful than comparable countries in pursuing both these objectives.

PMID- 17454924
TI  - Getting by with a little help: the importance of various types of social support
      for health problems.
AB  - AIMS: Our understanding of the relative importance of various types of social
      support is still limited. This study examines the overall and relative importance
      of various types of social support for health problems in a general population.
      The support resources focused on differ in character and represent companionship
      and emotional, instrumental, and informational types of social support. The
      health problems are depression, circulatory problems, and self-rated general
      health. METHODS: The logistic regression analyses are based on a Swedish
      nationally representative sample of 5,053 adults, aged 18-75, interviewed in the
      Level of Living Survey in 2000. Panel data from the earlier interview wave in
      1991 were also used. RESULTS: The number of support resources was associated with
      all the health problems studied. The availability of economic support was
      important relative to the other support resources (or of similar importance),
      irrespective of marital status, social class, and own economic situation. The
      associations hold when earlier health status was controlled for. Having someone
      to talk to about personal problems and having someone for company were relevant,
      especially the latter. This support resource demonstrated an association with all
      health problems, which remains when the other support resources and earlier
      health status are taken into consideration. CONCLUSIONS: In the Swedish
      population, the number of support resources was linked to health problems,
      indicating the usefulness of a diverse resource pool. The multidimensional
      approach revealed that economic support, company, and, to a more limited extent,
      the opportunity to discuss personal problems were most important.

PMID- 17454925
TI  - Public health policies: a Scandinavian model?
AB  - AIM: To identify how public health problems are identified, explained, and
      addressed in Scandinavian public health programmes. METHODS: Recent public health
      white papers from Denmark, Norway, and Sweden have been studied asking the
      following questions. How are policies and activities justified? Which problems
      and causes are identified? What is to be done? To what extent are the
      interpretations and suggested interventions in accordance with liberal or social
      democratic political ideals? RESULTS: The programmes studied give similar reasons
      for dealing with public health, namely the wish to create good lives for citizens
      and to improve the economy of society. The health problems identified are almost
      the same: cancer, heart disease, diabetes, musculoskeletal diseases, and mental
      illness. The Danish programme differs from its Norwegian and Swedish counterparts
      with regard to explanations and suggested solutions to the problems. It may be
      characterized as more liberal. While the Danish programme stresses the importance
      of individual behaviour, responsibility, and autonomy, the two others emphasize
      social relations, living conditions, and participation in addition to behavioural
      factors. Political responsibility for the health of the population is emphasized
      in the Norwegian and Swedish programmes. The Swedish programme, in particular,
      stresses common values such as equality and equal rights, and the significance of
      the welfare state. The Norwegian programme underlines the importance of
      empowering the individual, an ambition that could also be seen as a social
      liberal ambition to increase the self-determination of citizens. CONCLUSION:
      There is not one Scandinavian model in public health policy but several: a Danish
      model mainly adhering to liberal ideals, a Norwegian one that could tentatively
      be labelled social liberal, and a Swedish model adhering to more social
      democratic ideals.

PMID- 17454926
TI  - Does survey non-response bias the association between occupational social class
      and health?
AB  - AIMS: A non-response rate of 20-40%is typical in questionnaire studies. The
      authors evaluate non-response bias and its impact on analyses of social class
      inequalities in health. METHODS: Set in the context of a health survey carried
      out among the employees of the City of Helsinki (non-response 33%) in 2000-02.
      Survey response and non-response records were linked with a personnel register to
      provide information on occupational social class and long sickness absence spells
      as an indicator of health status. RESULTS: Women and employees in higher
      occupational social classes were more likely to respond. Non-respondents had
      about 20-30% higher sickness absence rates. Relative social class differences in
      sickness absence in the total population were similar to those among either
      respondents or non-respondents. CONCLUSIONS: In working populations survey non
      response does not seriously bias analyses of social class inequalities in
      sickness absence and possibly health inequalities more generally.

PMID- 17454927
TI  - Comparison of two items on self-rated health.

PMID- 17454928
TI  - Systematic review of ethnic variation in the phenotype of Behcet's disease.
AB  - OBJECTIVE: To systematically review the strength of evidence that supports the
      premise that there are different expressions in the clinical phenotype of
      Behcet's disease (BD) in different ethnic groups. METHODS: The hierarchy of
      evidence and inclusion criteria were decided prior to the search for relevant
      literature. We searched Medline and Embase databases between 1966 and March 2005
      for publications related to epidemiology of Behcet's disease or syndrome.
      Relevant papers were extracted in hard copy and the references of all these
      papers were then hand searched for further articles. RESULTS: Four population
      based studies, of which two were from Turkey, and seven non-population-based
      comparative studies were found. The majority of literature identified were case
      series and were not included in the review. There were insufficient cross
      sectional studies from different populations to be able to compare phenotypic
      differences. None of the comparative studies found evidence of a difference in
      the clinical expression of BD between ethnic groups. CONCLUSIONS: There is
      insufficient evidence to support the premise that there are different expressions
      in the clinical phenotype of BD in different ethnic groups. Population-based,
      cross-sectional surveys or case-control studies using standardized criteria and
      clear ethnic definitions are suggested to investigate this hypothesis further.

PMID- 17454929
TI  - Incidence of juvenile idiopathic arthritis in children in Estonia: a prospective
      population-based study.
AB  - OBJECTIVE: To study the incidence rate of juvenile idiopathic arthritis (JIA) and
      its clinical subtypes in Estonia, to follow the course of the disease in newly
      diagnosed patients for 2 years, and to find the frequency of human leucocyte
      antigens (HLA) B27, DR1 and DR4 in JIA patients. METHOD: A population-based study
      involving prospective registration of new cases of JIA in 1998-2000 and their
      clinical follow-up for 2 years. RESULTS: In 1998-2000, 162 new cases of JIA were
      diagnosed. The mean annual incidence rate of JIA was 21.7 per 100 000 children
      aged 0-15 years (22.9 in girls and 19.3 in boys). During the investigation
      period, the incidence rate rose 3.5-fold. Oligoarthritis was the most frequent
      subtype (mean annual incidence rate of 11.7 per 100 000), followed by
      seronegative polyarthritis (4.4 per 100 000). HLA-DR1, B27 and DR4 were found
      respectively in 44.4, 28.6 and 11.1% of cases in which the analysis was
      performed. In HLA-B27-positive patients, inflammation markers of blood remained
      at a high level for a longer period compared with HLA-B27-negative patients.
      CONCLUSIONS: This is the first population-based study on the epidemiology of
      juvenile arthritis in Estonia in which the new classification criteria defined by
      the International League of Associations for Rheumatology (ILAR) have been used.
      In addition to environmental factors, an increase in awareness among family
      doctors is a probable reason for the rise in incidence during the study period.
      HLA-B27 might have predictive value as a marker of chronicity of inflammation.

PMID- 17454930
TI  - Prevalence of spondyloarthropathies in an Italian population sample: a regional
      community-based study.
AB  - OBJECTIVE: To estimate the prevalence of spondyloarthropathies (SpA) in an adult
      population in Marche, a region located in central Italy. METHODS: A cross
      sectional population-based study was conducted on a target adult population of 20
      882. Questionnaires were sent to a random sample of 3664 individuals aged 18
      years and over, selected from the lists of 16 general practices. Trained
      rheumatologists carried out structured visits in which respondent subjects were
      asked about symptoms of back pain, peripheral arthritis, joint swelling,
      psoriasis, and the occurrence of diarrhoea and dysuria. A family history of
      rheumatic disease, psoriasis, or uveitis was assessed. Cases were further
      classified as ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive
      arthritis (ReA), inflammatory bowel disease (IBD)-associated arthritis, and
      undifferentiated SpA by the European Spondyloarthropathy Study Group (ESSG)
      criteria. RESULTS: A total of 2155 subjects participated to the study (response
      rate 58.8%). Twenty-three cases of SpA (18 men, five women, mean age 48.3 +/-
      12.1 years) were confirmed, with an overall prevalence of 1.06% [95% confidence
      interval (CI) 0.78-1.38]. The most common SpA was PsA, with a prevalence of 0.42%
      (95% CI 0.31-0.61), followed by AS with 0.37% (95% CI 0.23-0.49). Two cases with
      undifferentiated SpA, two with ReA, and two with IBD-associated arthritis were
      also observed (0.09%, 95% CI 0.04-0.16). CONCLUSIONS: This is the first
      population-based study that provides an estimate of the prevalence of SpA in
      Italy. PsA and AS were the most common SpA subsets. Further epidemiological
      studies are needed to obtain reliable prevalence rates and to better understand
      our findings.

PMID- 17454931
TI  - Adaptation of the Bath measures on disease activity and function in ankylosing
      spondylitis into Danish.
AB  - OBJECTIVE: Adaptation of the Bath Ankylosing Spondylitis Disease Activity Index
      (BASDAI), the Bath Ankylosing Spondylitis Global Score (BASG), and the Bath
      Ankylosing Spondylitis Functional Index (BASFI) for defining disease status in
      ankylosing spondylitis (AS) and related diseases for use in Denmark. METHODS: The
      BASDAI, BASFI, and BASG were translated into Danish and subsequently field-tested
      among 17 AS patients for relevance, face, and content validity. Reliability and
      validity were assessed by administering the new measures and a comparator
      instrument to 113 AS patients on two occasions. RESULTS: Test-retest reliability
      was high (>0.90) and the random measurement error was within+/-2.0 for the BASG
      and within approximately+/-1.5 for BASDAI and BASFI, which is acceptable for most
      clinical settings. The measures have good internal consistency and are able to
      discriminate between functional impairment and disease activity according to the
      Nottingham Health Profile (NHP) and the Stanford Health Assessment Questionnaire
      (HAQ). CONCLUSION: Danish versions of the BASG, BASDAI, and BASFI are feasible
      for application in clinical trials and epidemiological studies on AS in Denmark.

PMID- 17454932
TI  - Yersinia-triggered arthritis in IL-12p40-deficient mice: relevant antigens and
      local expression of Toll-like receptor mRNA.
AB  - OBJECTIVES: To study the role of IL-12p40 at the onset of reactive arthritis
      (ReA) after Yersinia enterocolitica O:3 infection, and analyse relevant microbial
      antigens and articular expression of Toll-like receptor (TLR) mRNA. METHODS: Wild
      type C57BL/6 and IL-12p40-deficient (IL-12p40-/-) mice were orogastrically
      infected with Y. enterocolitica O:3. Early (day 3) and late (day 21) after
      infection, the number of bacteria were determined in Peyer's patches (PP),
      mesenteric lymph nodes (MLN), the spleen, and joints. Histological studies of
      joints were performed. Collagen-specific and anti-Yersinia antibodies were
      measured by enzyme-linked immunosorbent assay (ELISA). The presence of Yersinia
      antigens was studied by dot blot. Induction of articular mRNA of TLR2, TLR4, and
      tumour necrosis factor (TNF)-alpha was analysed by reverse transcription
      polymerase chain reaction (RT-PCR). TNFalpha protein levels were measured by
      ELISA. RESULTS: At day 3, bacterial recovery in PP, MLN, and spleen was
      significantly increased in IL-12p40-/- mice. Histopathological changes were
      observed in IL-12p40-/- mice at day 21 after infection, and correlated with
      higher antibody response against type II collagen. Although live bacteria could
      not be isolated at day 21 after infection, articular microbial components,
      especially from the outer membrane (OM), were detected. Moreover, intra-articular
      immunoglobulins to Yersinia antigens were significantly higher in IL-12p40-/-
      mice. Furthermore, mRNA levels for TLR2, TLR4 and TNFalpha, and TNFalpha protein
      were increased in joints from IL-12p40-/- mice. CONCLUSIONS: We concluded that IL
      12p40 influences the resistance against Yersinia-triggered ReA. Bacterial
      products such as Yersinia OM could contribute to the ReA by induction of
      articular TLR expression, which results in an inflammatory response in the joint.

PMID- 17454933
TI  - Evaluation of haemodynamic flow to the hip in patients with systemic lupus
      erythematosus.
AB  - OBJECTIVE: One of the groups with high risk for osteonecrosis is patients with
      systemic lupus erythematosus (SLE). No predictive test, however, is known to
      detect osteonecrosis. The purpose of this study was to evaluate haemodynamic flow
      to the proximal femur in SLE patients. METHODS: Twenty-two SLE patients without
      osteonecrosis were evaluated in comparison with 15 healthy controls. Medial and
      lateral circumflex arteries of 44 hips in the 22 SLE patients and 30 hips in the
      healthy controls were examined using ultrasound equipment with colour and power
      Doppler capability. Arterial pulsatility index (PI) and peak systolic velocity
      (PSV) were determined with neutral and internal rotation positions (stimulated
      ischaemia). RESULTS: PSV was significantly increased in SLE patients compared to
      healthy controls in both the neutral position (70.6+/-40.4 vs. 46.9+/-19.3;
      p<0.001) and after internal rotation of the femoral head (74.8+/-42.3 vs. 49.9+/
      19.9; p<0.001). PI was also higher in SLE patients than in healthy controls in
      both the neutral position (8.9+/-6.3 vs. 5.5+/-3.4; p<0.001) and after internal
      rotation (8.1+/-7.1 vs. 3.9+/-2.4; p<0.001). CONCLUSION: PSV and PI of arteries
      to the femur head in SLE patients were significantly higher than in healthy
      controls.

PMID- 17454934
TI  - Body composition, lipid and lipoprotein levels in childhood-onset systemic lupus
      erythematosus.
AB  - OBJECTIVES: Systemic inflammation, corticosteroid therapy, and reduced physical
      activity are risk factors for altered body composition in patients with systemic
      lupus erythematosus (SLE). The aim of this study was to assess whether body
      composition differs between childhood-onset SLE patients and healthy controls,
      and to investigate the impact of disease characteristics and lifestyle factors on
      body fat mass, serum lipids, and lipoproteins. METHODS: Fat mass and lean tissue
      mass were measured in a cross-sectional study of 68 childhood-onset SLE patients
      and 68 matched healthy controls by dual-energy X-ray absorptiometry (DXA). The
      influence of disease, glucocorticosteroids, disease activity and severity,
      physical activity, and dietary intake on fat mass was evaluated by multiple
      linear regression analysis. Serum lipid and lipoprotein levels were measured.
      RESULTS: Patients had a significantly higher fat mass [mean (SD) 35.3 (10.8) vs.
      30.9 (11.1)%; p = 0.024] and lower lean mass [39.7 (9.8) vs. 44.4 (1.5) kg; p =
      0.003] than controls. Corticosteroid use and the disease itself were significant
      independent predictors of greater fat mass, while disease activity, physical
      activity, and dietary intake had only a minor influence. Mean high density
      lipoprotein (HDL) cholesterol and apolipoprotein A1 (apo A1) levels were
      significantly lower (p<0.001), and the mean apo B/apo A1 ratio significantly
      higher (p = 0.004), in patients than in controls. CONCLUSION: Childhood-onset SLE
      patients had a higher fat mass and lower lean mass than healthy controls and
      corticosteroid use was an independent predictor of increased fat mass. Patients
      had a more proatherogenic lipid profile, which will contribute to the increased
      risk of coronary heart disease in SLE patients.

PMID- 17454935
TI  - Common FMF alleles may predispose to development of Behcet's disease with
      increased risk for venous thrombosis.
AB  - BACKGROUND: Behcet's disease (BD) is an inflammatory disorder of unknown cause,
      associated with vasculitis. Arterial or venous thrombosis occurs in about 25% of
      BD patients. Familial Mediterranean fever (FMF) is another inflammatory disorder,
      which stems from mutations in the FMF gene (MEFV) and shares a number of features
      with BD. OBJECTIVE: MEFV analysis in patients with BD suggests that mutated MEFV
      may act as a susceptibility gene in BD. We studied the rate and the clinical
      correlates of MEFV mutations in Israeli BD patients. METHODS: Included were 54 BD
      patients who satisfied the International Study Group criteria for BD. All BD
      patients were genotyped using polymerase chain reaction (PCR) and restriction
      enzyme analysis for the three most common MEFV mutations (M694V, V726A, and
      E148Q). The association between BD manifestations and MEFV alleles was analysed.
      RESULTS: Twenty-one BD patients were found to carry a single MEFV mutation and
      three additional patients were compound heterozygotes, a frequency significantly
      higher than that expected for ethnically matched healthy individuals. There were
      no statistically significant differences between carriers and non-carriers with
      respect to gender, frequency of HLA B5 antigen, cutaneous lesions, joint disease,
      and severity score. However, carriers did experience thrombosis more often [54%
      vs. 17%, p<0.005, odds ratio (OR) = 6.9, 95% confidence interval (CI) 1.75-26.9]
      and uveitis less often (20% vs. 40%, p<0.05, OR = 0.2, 95% CI 0.04-0.92).
      CONCLUSIONS: MEFV appears to be a susceptibility and modifier gene in BD.

PMID- 17454936
TI  - Age, body composition, and reproductive indices as predictors of radiographic
      hand osteoarthritis in Chuvashian women.
AB  - OBJECTIVES: In our observational cross-section population-based study, we
      evaluated the predictors (age, body composition indices, age at menarche, and age
      at menopause) of radiographic hand osteoarthritis (OA) from a sample of women of
      European origin, who were not receiving any medication for prevention or
      treatment of OA. METHODS: Our population consisted of 745 Chuvashian females with
      a mean age of 48.65 years (range 18-84 years) residing in peripheral villages of
      the Russian Federation. OA was evaluated using the Kellgren and Lawrence grading
      scheme. To evaluate the relationship between age, age at menarche, age at
      menopause, body composition indices [body mass index (BMI), waist circumference
      (WC), waist-hip ratio (WHR), somatotypes (ectomorphy, mesomorphy, and
      endomorphy)], and an individual's osteoarthritis score (Tot28) as the dependent
      variable, we used multiple linear regression analysis (stepwise method). RESULTS
      AND CONCLUSIONS: Statistically significant predictors of hand OA in women were
      found to be the following: age (beta = 0.748, p = 0.000), mesomorphy (beta =
      0.120, p = 0.000), WHR (beta = 0.117, p = 0.001), endomorphy (beta = -0.089, p =
      0.006), and age at menarche (beta = -0.066, p = 0.012). Age was the most powerful
      factor in determining hand OA. Mesomorphy, the measure of muscular development
      was a significant predictor of hand OA. Endomorphy showed a very small, but
      significant, negative association with hand OA. However, BMI and WC showed no
      association, leading us to conclude that obesity is a mechanical rather than a
      systematic risk factor for OA. Age at menarche was negatively associated with
      hand OA, possibly because early menarche is associated with an increased rate of
      the general ageing process.

PMID- 17454937
TI  - Agreement between clinical and radiological methods of diagnosing knee
      osteoarthritis.
AB  - OBJECTIVE: To determine the agreement between clinical diagnosis and different
      radiological grading scales of knee osteoarthritis (OA) in an epidemiological
      study. METHODS: Health 2000 Survey is an extensive population study focusing on
      major health problems in a representative sample of 8028 Finns over 30 years of
      age. In the survey, physicians diagnosed knee OA on the basis of physical status,
      symptoms, and medical history. A total of 130 participants (mean age 60 years,
      68% female) were re-examined 1 year later (Kuopio OA 2000 Study) to determine the
      agreement between clinical and radiological diagnosis as well as between three
      different radiological grading scales (Kellgren and Lawrence, Ahlback, and
      Piperno). Weight-bearing knee radiographs were taken and graded by a radiologist
      in Kuopio University Hospital. The history of knee symptoms was obtained using
      the Western Ontario MacMaster (WOMAC) and Lequesne questionnaires. RESULTS: Knee
      OA was diagnosed clinically in 17.7% and radiologically in 24.6-30% of
      participants. The strength of agreement was moderate (kappa values 0.34-0.54)
      between the clinical and the radiological diagnosis and substantial (0.62-0.78)
      between the different radiological scales. Those subjects identified by any
      diagnostic method as having OA in either knee reported significantly more
      symptoms and disability than the other subjects. CONCLUSION: The agreement
      between the clinical diagnosis performed in a large population study and
      radiological grading scales was only moderate. By contrast, the agreement between
      different radiological scales was substantial.

PMID- 17454938
TI  - Methotrexate-related lymphomatoid granulomatosis: a case report of spontaneous
      regression of large tumours in multiple organs after cessation of methotrexate
      therapy in rheumatoid arthritis.
AB  - We describe a 54-year-old female patient with rheumatoid arthritis (RA) and
      Sjogren's syndrome (SS) who presented with right chest pain and a large mass
      visible in the upper right field of a chest X-ray. Computed tomography (CT)
      showed multiple tumours in both lungs, the liver, and the spleen. The right lung
      tumour was 8 cm in diameter with a cavity. Biopsy of the lung and liver revealed
      lymphomatoid granulomatosis (LG) and diffuse large B-cell lymphoma (DLBCL). These
      lesions spontaneously regressed after withdrawal of methotrexate without any
      therapy for the lymphoma. This is the first report of self-limiting LG in a
      patient, complicated with methotrexate-treated RA.

PMID- 17454939
TI  - Systemic sclerosis sine scleroderma associated with Wolff-Parkinson-White
      syndrome.
AB  - The term "systemic sclerosis sine scleroderma" (ssSSc) has been used to designate
      a rare progressive systemic sclerosis of visceral organs without skin
      manifestations. A variety of visceral organs, including the gastrointestinal
      tract, lung, heart, and kidney, can be involved. We describe a case of 59-year
      old female patient with both Wolff-Parkinson-White (WPW) syndrome and ssSSc. She
      was diagnosed as having ssSSc with Raynaud's phenomenon, anti-nuclear antibody
      (ANA) and anti-topoisomerase antibody positivity, interstitial pulmonary
      infiltrates, suspected pulmonary hypertension, subclinical oesophageal
      dysmotility but no skin thickening. She had a history of paroxysmal tachycardia
      together with Raynaud's phenomenon and exercise-induced dyspnoea.
      Electrophysiological study confirmed WPW syndrome with left posterior bypass
      tract. This case highlights cardiac arrhythmia caused by WPW syndrome as a
      clinical manifestation of the heart in ssSSc.

PMID- 17454940
TI  - Cogan's syndrome with recurrent carotid and aortic aneurysms: a potentially fatal
      disorder mimicking Marfan syndrome.
AB  - Cogan's syndrome (CS) is a rare multisystemic disease characterized by
      vestibuloauditory dysfunction, inflammatory eye disease and vasculitis. Aortic
      aneurysms due to aortitis are under-recognized in CS, and are potentially fatal,
      with two of eight reported cases dying from aneurysm/arterial rupture. The
      presence of aneurysms was not recognized antemortem in both cases, highlighting
      the importance of early detection to prevent this potentially fatal outcome. We
      report a 17-year-old Chinese male with recurrent carotid and aortic aneurysms,
      bilateral sensorineural hearing loss, and recurrent scleritis who was initially
      thought to have Marfan syndrome. The diagnosis of CS was made 4.5 years after
      initial presentation, during which time recurrent aneurysms due to active
      aortitis (with aneurysmal rupture on one occasion) necessitated four surgical
      procedures. Treatment with methotrexate and corticosteroids resulted in no
      recurrence of aneurysms over 2 years of follow-up. This case illustrates (i) the
      challenges in diagnosing CS when various manifestations occur separately over a
      relatively long time period, (ii) that detection of aortic aneurysms in young
      patients, especially if recurrent, should prompt investigations for
      vasculitis/aortitis to prevent potentially fatal aneurysm rupture, and (iii) that
      methotrexate and high-dose corticosteroids may be effective in preventing
      development of further aneurysms in CS patients.

PMID- 17454941
TI  - Clinical features of ANCA-positive systemic lupus erythematosus: report of two
      cases.

PMID- 17454942
TI  - Adult Still's disease patient developed thrombotic microangiopathy with diffuse
      digital gangrene.

PMID- 17454943
TI  - Severe digital ischaemia in a child with Wegener's granulomatosis.

PMID- 17454944
TI  - Bax and Bcl-2 are focally overexpressed in the normal epithelium of cancerous
      prostates.
AB  - OBJECTIVE: Development of prostate cancer is connected with a disturbance of
      apoptosis. Prostate cancer is multifocal, suggesting that the control of
      apoptosis is impaired at multiple foci. We wanted to know whether apoptosis is
      generally disturbed in cancerous prostates and if changes in apoptotic control
      could be detected even in the absence of any morphologically visible changes.
      Therefore, we compared expression of two common apoptotic markers, Bax and Bcl-2,
      in normal epithelium of cancerous prostates and controls. We also evaluated the
      expression of these proteins in hyperplasia, prostatic intraepithelial neoplasia
      (PIN), carcinomas of different Gleason grades and capsular perineural invasion.
      MATERIAL AND METHODS: The tissue material was obtained from radical
      prostatectomies, transurethral resection chips and autopsies. Individual tissue
      arrays were done for each patient. The intensity of Bax and Bcl-2 immunostaining
      was estimated semiquantitatively. The data were analyzed using a linear mixed
      models analysis as well as dichotomized staining indices. RESULTS: Normal
      epithelium of cancerous prostates contained foci with high expression of Bax and
      Bcl-2. The expression of Bax in Gleason grades 3-5 carcinoma was significantly
      higher than that in Gleason grade 2, and was highest in foci with perineural
      invasion. The expression of Bcl-2 was strongest in PIN foci. CONCLUSIONS:
      Expression of Bax and Bcl-2 in normal epithelium of cancerous prostates suggests
      that increases in these indirect markers may reflect altered apoptotic control in
      these foci. Further studies are needed to show whether these changes represent
      the earliest step of the multifocal carcinogenetic process. Control of apoptosis
      seems to be involved and modulated during local progression of prostate cancer.

PMID- 17454945
TI  - Comparison of the effects of captopril, tamoxifen and L-carnitine on renal
      structure and fibrosis after total unilateral ureteral obstruction in the rat.
AB  - OBJECTIVE: To compare the effects of captopril, tamoxifen and L-carnitine on
      renal structure and the collagen content of the unilateral obstructed kidney in
      the rat using unbiased stereological methods. MATERIAL AND METHODS: Rats (n=25)
      were assigned equally to one of five groups after ligation of the ureter: (i)
      normal controls (no hydronephrosis); (ii) positive controls (hydronephrotic rats
      without drug treatment); (iii) hydronephrotic rat with captopril treatment (CAP);
      (iv) hydronephrotic rats with L-carnitine treatment (L-CAR); and (v)
      hydronephrotic rats with tamoxifen treatment (TAM). Two weeks after unilateral
      ureteral obstruction the kidney was removed and histological sections were
      prepared. The kidney volume and the fractional volumes and absolute amounts of
      the cortex, medulla, tubules, renal corpuscles, vessels and fibrous tissue were
      determined using modern stereological techniques. RESULTS: Kidney volume
      increased in the CAP group in comparison with the other groups. The absolute
      volume of the tubules was the same in the CAP group compared to the normal
      control group. However, in the other experimental groups, the amount of tubules
      decreased. The absolute volumes of the renal corpuscles and vessels did not show
      any significant differences between groups. The absolute volume of fibrous tissue
      showed significant increases in all groups in comparison with the normal
      controls. There were no differences in the absolute amounts of fibrous tissue
      between the positive control, CAP and L-CAR groups, but in the TAM group the
      collagen content was decreased. CONCLUSIONS: Captopril preserved the amount of
      renal tubules and tamoxifen decreased fibrous tissue formation in unilateral
      obstructed kidneys but there were no differences in other hydronephrotic kidneys.

PMID- 17454946
TI  - Tibial nerve stimulation diminishes mast cell infiltration in the bladder wall
      induced by interstitial cystitis urine.
AB  - OBJECTIVES: To investigate whether the urine of interstitial cystitis (IC)
      patients has a toxic effect on the bladder wall, as determined by mast cell
      infiltration, and to evaluate the preventive effect of tibial nerve electric
      stimulation (TNES) on bladder mastocytosis induced by IC urine. MATERIAL AND
      METHODS: The bladders of female rats were catheterized and instilled with IC
      urine (Group IC; n=10) and normal urine (Group NU; n=5) obtained from humans,
      saline (Group S; n=5) and protamine sulphate (Group PS; n=10) for 6 weeks.
      Additionally, in five rats instilled with IC urine and five instilled with PS,
      TNES was also performed (Groups IC + TNES and PS + TNES). RESULTS: In the lamina
      propria of the bladder, the mean number of mast cells per square millimetre was
      significantly higher in Groups IC (32.5+/-12.3) and PS (39.4+/-11.1) than in
      Groups S (11.9+/-4.3) and NU (13.7+/-3.5). After TNES, the corresponding values
      were decreased significantly to 15.3+/-5.4 and 15.3+/-4.1 in Groups IC + TNES and
      PS + TNES, respectively (p<0.001). A significant reduction in mast cell
      infiltration in the detrusor was also determined after TNES compared with the
      value in Group IC (4.6+/-1.6 vs 12.1+/-3.0; p<0.001). CONCLUSIONS: We
      demonstrated that IC urine may result in increased mast cell infiltration in the
      bladder wall. TNES may play a therapeutic role by diminishing the mast cell count
      in the bladder wall, which has a strong relationship with nociceptive neural
      endings.

PMID- 17454947
TI  - Long-term follow-up of conservatively managed incidental carcinoma of the
      prostate: a multivariate analysis of prognostic factors.
AB  - OBJECTIVE: To evaluate the disease-specific mortality of conservatively managed
      incidental carcinoma of the prostate (T1a and T1b) in relation to prognostic
      factors. MATERIAL AND METHODS: Since 1987 all patients with prostate cancer have
      been recorded and followed in the population-based Prostate Cancer Register of
      the South-East Healthcare Region in Sweden, which is covered by four departments
      of pathology. At two of these departments, tissue was obtained from 197
      consecutive, previously untreated patients (aged <80 years) with incidental
      carcinoma who underwent transurethral resection of the prostate between 1987 and
      1991. The amount of tumour, Gleason score and levels of Ki-67, p53, chromogranin
      A and serotonin were determined. Univariate analysis and multiple Cox regression
      hazard analysis were used for analysis. RESULTS: During follow-up (mean 7.8
      years; maximum 17.5 years), 158 patients (80%) had died, 33 of them of prostate
      cancer, corresponding to 17% of the entire cohort. Of 86 patients with Gleason
      score < or =5, three died of prostate cancer. Independent predictors of disease
      specific mortality in multivariate analysis were category T1b prostate cancer,
      Gleason score >5 and high immunoreactivity of Ki-67. CONCLUSIONS: Elderly men
      with category T1a and/or Gleason score 4-5 prostate cancer have a favourable
      prognosis with conservative management. Immunohistochemical staining with Ki-67
      may be of help in situations where further prognostic information is required.

PMID- 17454948
TI  - Shift in imaging modalities of the urinary tract over a 25-year period and its
      impact on ionizing radiation doses given to patients.
AB  - OBJECTIVES: To explore the shift in imaging modalities used when examining the
      urinary tract over the period 1979-2003 and to see how this shift, together with
      a radiation protection policy, have influenced the doses of ionizing radiation
      used. MATERIAL AND METHODS: Activity reports from a department of radiology were
      reviewed. Relevant radiation dose estimates were obtained from the Norwegian
      Radiation Protection Authority. RESULTS: Ultrasound (US) was introduced in 1983
      and has been increasingly used since then. MRI was introduced in 1992 and has
      been used to some extent when examining the urinary tract. The use of i.v.
      pyelography decreased by 50% during the review period and the use of plain
      radiographs remained practically unchanged. The number of CT examinations
      increased until 1983, but decreased thereafter. The total number of examinations
      of the urinary tract has increased during the review period, but the radiation
      doses given have decreased. CONCLUSIONS: The introduction of US and MRI, together
      with a radiation protection policy, have reduced the ionizing radiation doses
      given to this population, in spite of an increase in the total number of
      examinations of the urinary tract.

PMID- 17454949
TI  - Urinary calculi following traumatic spinal cord injury.
AB  - OBJECTIVE: To investigate the time aspect of the development of renal and bladder
      calculi in individuals with traumatic spinal cord injury (SCI) and a possible
      relation between the development of calculi and the bladder-emptying method.
      MATERIAL AND METHODS: The study comprised a retrospective data collection from
      medical records and a questionnaire follow-up at least 10 years after the SCI.
      RESULTS: A total of 236 individuals with SCI (82% male, 18% female; 47%
      tetraplegic, 53% paraplegic) who were injured between 1956 and 1990 participated
      in the study and the response rate was 84.6%. The mean age at the time of follow
      up was 50.5 years (range 28-84 years). The mean duration from the time of SCI was
      24.1 years (range 10-45 years). During follow-up 47 participants (20%) had at
      least one episode of renal calculi and 32 (14%) had at least one episode of
      bladder calculi. The risk of first renal and bladder calculus was highest within
      the first 6 months post-injury. The cumulative proportion of calculi-free
      participants 45 years post-injury was 62% for renal calculi and 85% for bladder
      calculi. For participants who did not develop renal calculi within the first 2
      years post-injury, the risk of having a renal calculus within the next 43 years
      was 34%. For bladder calculi the corresponding risk of having a bladder calculus
      within the next 43 years was 5%. No significant differences were found regarding
      the bladder-emptying method and either renal or bladder calculi, only a non
      significant trend that more participants with bladder calculi used indwelling
      catheters. Participants with renal or bladder calculi were not statistically
      significantly different from the remainder of the study group regarding gender,
      para- or tetraplegia or Frankel classification. CONCLUSIONS: The risk of
      developing renal and bladder calculi was higher in the SCI population compared to
      the normal population. Bladder calculi primarily occur early post-injury and
      renal calculi appear both early post-injury and years later. Therefore, it is
      important to follow individuals with SCI regularly by means of urological
      investigations from the time of the injury until death.

PMID- 17454950
TI  - Men with spinal cord injury have a smaller prostate than men without.
AB  - OBJECTIVE: To compare prostate volume and number of ejaculations in men with and
      without spinal cord injury (SCI). MATERIAL AND METHODS: A total of 31 men aged >
      or =30 years who had suffered from SCI at the age of 15-30 years >5 years
      previously were investigated and compared with 31 age-matched controls. Prostate
      size was measured using transrectal ultrasound and compared between groups.
      Hormonal status was examined by measuring the levels of prostate-specific
      antigen, testosterone, prolactin, estradiol and sex hormone-binding globulin.
      Questions were asked concerning ejaculatory function. RESULTS: Median prostate
      size was 20.4 cm(3) (range 9.9-39.7 cm(3)) in the SCI group and 25.7 cm(3) (range
      14.5-39.1 cm(3)) in the control group (p=0.002). Testosterone levels were within
      normal ranges, but a significant difference between the groups was seen
      (p<0.001). The free androgen index did not differ significantly between the
      groups. No significant differences in other hormone levels were demonstrated. The
      control group ejaculated a median of eight times per month (range 1-28 times).
      Eight men with SCI ejaculated without assistance a median of twice per month
      (range <1-12 times) (p=0.028). Nine men with SCI achieved ejaculations with
      penile vibratory stimulation a median of once per month (range <1-4 times)
      (p=0.004). Fourteen men had either not ejaculated at all or very seldom following
      the injury. CONCLUSIONS: Men with SCI have a smaller prostate than those without.
      Further investigations are necessary to elucidate whether the reduced number of
      ejaculations they experience and the neurological damage contribute to this.

PMID- 17454951
TI  - Long-term cost analysis of treatment options for benign prostatic hyperplasia in
      Norway.
AB  - OBJECTIVE: To estimate and compare the costs of dutasteride, finasteride,
      tamsulosin and transurethral resection of the prostate (TURP) for benign
      prostatic hyperplasia (BPH) from a Norwegian health service perspective. MATERIAL
      AND METHODS: A Markov model was developed to estimate the clinical progression
      that a cohort of 1000 men would undergo and the care they would receive over 4-
      and 15.5-year periods. Transitions between health states [BPH symptoms,
      improvement in symptoms, acute urinary retention (AUR), TURP, prostate cancer and
      death] were estimated from the published literature and knowledge of the
      Norwegian healthcare system. Sensitivity analyses were conducted of indirect
      costs, discount rates, the costs and probabilities of AUR and TURP and the
      probability of symptom improvement. RESULTS: The total costs of BPH management
      for patients initially treated with dutasteride, finasteride, tamsulosin or TURP
      at 4 years were NOK 13,946 (1703 Euro), NOK 16,111 (1967 Euro), NOK 16,833 (2054
      Euro) and NOK 46,309 (5655 Euro), respectively and at 15.5 years NOK 32,137 (3924
      Euro), NOK 37,173 (4539 Euro), NOK 40,528 (4946 Euro) and NOK 50,471 (6164 Euro),
      respectively. One- and multi-way sensitivity analyses did not significantly alter
      the relative order of the total costs. CONCLUSIONS. Given the conservative nature
      of the model and the robustness of the sensitivity analysis, it is concluded that
      dutasteride is less costly than finasteride, TURP or tamsulosin at both 4 and
      15.5 years. Therefore, considering cost containment restraints in Norway,
      dutasteride is an appropriate choice of therapy for patients with moderate/severe
      symptoms and an enlarged prostate (>30 ml).

PMID- 17454952
TI  - Maximal functional electrical stimulation as a single treatment: is it cost
      effective?
AB  - OBJECTIVE: The ideal electrical parameters for maximal functional electrical
      stimulation (MFES) in the treatment of an overactive bladder have not yet been
      well established. It has been speculated that unsatisfactory results may be due
      to a low stimulation intensity and that the number of sessions may also be an
      outcome-determining factor. Herein, we present the results obtained in a group of
      consecutively treated patients who were given 10 sessions of MFES at the highest
      tolerable amplitude. MATERIAL AND METHODS: A total of 60 patients (29 females, 31
      males) with an overactive bladder were treated. All subjects underwent a
      urodynamic assessment and completed a 48-h micturition chart prior to treatment,
      immediately after the last session and 3 months after termination of treatment.
      The patients were thoroughly informed that the result of the treatment depended
      on the amplitude that they could endure; there was a gradual increase in
      amplitude to the maximum level that did not cause painful discomfort. RESULTS:
      Immediately after termination of the stimulation, almost half of the subjects
      reported an improvement in their condition. However, few subjects experienced
      sustained symptom amelioration 3 months post-stimulation. Decreases in
      micturition frequency and the number of leakage episodes were noted immediately
      after cessation of treatment but these decreases were no longer significant 3
      months post-treatment. CONCLUSIONS: In this series, although MFES was effective
      in the short term, the long-term treatment outcome was unsatisfactory. A critical
      review suggests that outcome success is proportional to the patient's ability and
      willingness to accept quite a high stimulation intensity or, alternatively,
      follow-up home treatment. Hence, the implementation of strict primary as well as
      secondary selection criteria can hopefully identify patients most suitable for
      MFES. Another lesson to be learnt is that the identification of crucial
      prerequisites of successful treatment is mandatory before embarking on controlled
      studies.

PMID- 17454953
TI  - Effect of detrusor function on the therapeutic outcome of a suburethral sling
      procedure using a polypropylene sling for stress urinary incontinence in women.
AB  - OBJECTIVE: To assess the effect of detrusor function on the therapeutic outcome
      of a suburethral sling procedure in women with stress urinary incontinence (SUI).
      MATERIAL AND METHODS: A total of 192 women with SUI who had undergone a
      suburethral sling procedure were enrolled. According to the baseline urodynamic
      results, patients' bladder functions were classified as follows: (i) normal
      detrusor function; (ii) detrusor overactivity; and (iii) detrusor underactivity
      or acontractile detrusor. Surgical results, urodynamic parameters and patient
      satisfaction were compared among these three groups. RESULTS: Overall, 106
      patients had normal detrusor function, 36 had detrusor overactivity and 50 had
      detrusor underactivity or an acontractile detrusor. A continent outcome was
      achieved in 135 women (70.3%), urge incontinence in 23 (12%), minimal SUI in 32
      (16.7%) and moderate SUI in two (1%). Persistent urge incontinence was noted in
      13 women (36%) with detrusor overactivity, and recurrent SUI occurred in 18 women
      (36%) with detrusor underactivity or an acontractile detrusor. No significant
      change in urodynamic parameters between baseline and after treatment was found in
      any of the patient groups. The satisfaction rate was 98.1% in patients with
      normal detrusor function, 82% in patients with detrusor underactivity or an
      acontractile detrusor and 75% in patients with detrusor overactivity (p<0.05).
      CONCLUSION: Compared to women with normal detrusor function, those with
      preoperative detrusor overactivity and those with detrusor underactivity or an
      acontractile detrusor experienced an unfavorable therapeutic outcome of the
      suburethral sling procedure in terms of urge incontinence and recurrent SUI after
      surgery.

PMID- 17454954
TI  - Hypercalciuria in pediatric patients with ureteropelvic junction obstruction is
      of genetic origin.
AB  - OBJECTIVE: Genitourinary tract malformations are associated with urolithiasis.
      Hypercalciuria has been described in children with ureteropelvic junction
      obstruction (UPJO), although the etiology of this metabolic abnormality remains
      unknown. This study was conducted to find out whether children with UPJO have a
      higher prevalence of hypercalciuria and whether their family members are affected
      by hypercalciuria and/or urolithiasis. MATERIAL AND METHODS: We studied the
      prevalence of hypercalciuria and urolithiasis in 27 children (14 males, 13
      females) with UPJO and their parents. RESULTS: One patient had a history of renal
      colic, whereas imaging studies showed macroscopic renal lithiasis in two patients
      and calyceal microlithiasis in four. Hypercalciuria was found in 17/27 children
      (63%), 15 of whom (88%) had a familial history of urolithiasis: seven families in
      first-degree relatives, six in second-degree relatives and two in other
      relatives. Concerning the 10 children without hypercalciuria, seven of them (70%)
      had a family history of urolithiasis: four in first-degree relatives and three in
      second-degree relatives. The prevalences of both urolithiasis and hypercalciuria
      were not influenced by gender. CONCLUSIONS: Urolithiasis is associated with
      hypercalciuria in patients with UPJO. In accordance with previous data, our
      results show that the prevalence of hypercalciuria is greater in pediatric
      patients with UPJO than in the general population. Likewise, the prevalence of
      urolithiasis in the families of these children is also higher than that in the
      general population. Hypercalciuria was inherited as an autosomal dominant trait.

PMID- 17454956
TI  - Changes in pulmonary function in patients with chronic renal failure after
      successful renal transplantation.
AB  - OBJECTIVE: Pulmonary function abnormalities have been described in patients with
      chronic renal failure. There are very few longitudinal studies showing the effect
      of renal transplantation on pulmonary function. We aimed to study the effects of
      renal failure on pulmonary functions and to observe the changes following
      successful renal transplantation. MATERIAL AND METHODS: Patients with end-stage
      renal failure (n=25) of various etiologies who presented to the renal transplant
      unit of a teaching hospital were included in this prospective, longitudinal
      study. Patients with a prior history of pulmonary disease and chronic smokers
      were excluded. Pulmonary function tests were performed and blood gases evaluated
      before and 6 months after successful renal transplantation. RESULTS: Most
      patients showed pulmonary function abnormalities which improved significantly
      after transplantation. The mean vital capacity increased from 2.89 (95% CI 2.63
      3.15) l pre-transplantation to 3.32 (95% CI 3.09-3.54) l post-transplantation
      (p<0.001), indicating that subjects had a restrictive pulmonary function defect
      which improved after transplantation. The large airways were normal, as evidenced
      by normal forced expiratory volume in the first second:forced vital capacity
      ratios. There was significant small airways dysfunction, as shown by low maximal
      mid-expiratory flow rates, which tended to improve after renal transplantation
      (p=0.013). There was also a highly significant (p<0.001) improvement in maximal
      voluntary ventilation (MVV) after transplantation. The MVV test is a composite
      test which measures all aspects of pulmonary function, including respiratory
      muscle strength. However, not all patients achieved normal pulmonary function due
      to uremia-induced irreversible pre-transplantation changes. CONCLUSION: Pulmonary
      function abnormalities are common in patients with chronic renal failure but can
      be significantly ameliorated following successful renal transplantation.

PMID- 17454955
TI  - Evaluation of atrial and brain natriuretic polypeptides in association with
      angiotensin-converting enzyme gene polymorphism in Japanese non-diabetic
      hemodialysis patients.
AB  - OBJECTIVE: Insertion (I)/deletion (D) polymorphisms in the angiotensin-converting
      enzyme (ACE) gene have the potential to serve as a marker for an increased risk
      of cardiovascular events. Increased plasma levels of human atrial natriuretic
      polypeptide (ANP) and brain natriuretic polypeptide (BNP) are important indexes
      of cardiac function. The aim of this study was to examine possible relationships
      between I/D polymorphisms and the myocardial release of ANP and BNP in Japanese
      hemodialysis (HD) patients (n=131). MATERIAL AND METHODS: We studied 131 non
      diabetic hemodialysis patients. The genotype of ACE gene was determined by
      polymerase chain reaction with a set of specific timers. ANP and BNP levels were
      measured before HD. RESULTS: The plasma levels of ANP and BNP were significantly
      lower in the DD genotype group compared to those in the II group. Corresponding
      levels in the ID genotype group were intermediate between those in the DD and II
      groups. ACE polymorphism was associated with neither ejection fraction nor left
      ventricular mass/height index (LVMI), as evidenced by echocardiographic findings
      (n=107). Plasma levels of ANP were significantly correlated with left atrial
      diameter (LAD) in patients as a whole, but this correlation was only observed in
      the II genotype group, and not in the DD or ID groups. Plasma levels of BNP were
      significantly correlated with LAD, left ventricular end systolic diameter and
      LVMI in patients as a whole, but these correlations were seen only in the II
      genotype group. CONCLUSION: The results suggest that the plasma levels of these
      natriuretic peptides should be evaluated on the basis of ACE polymorphism for
      assessing cardiac diseases due to volume overload in Japanese HD patients.

PMID- 17454957
TI  - Oxypurine and nucleoside concentrations in renal veins during reperfusion are
      predictors of early graft function.
AB  - OBJECTIVE: To examine whether purine and pyrimidine nucleoside concentrations as
      well as oxypurine concentrations in renal and peripheral veins during reperfusion
      correlate with graft function parameters. MATERIAL AND METHODS: The study
      population comprised 25 recipients of cadaver kidney transplant. A first blood
      sample was taken from the recipient's peripheral vein before anastomosing the
      kidney allograft vessels with the recipient's iliac vessels. Subsequent samples
      were taken from the allograft renal vein and the recipient's peripheral vein 5
      min after beginning reperfusion. High-performance liquid chromatography was done
      to measure plasma concentrations of the oxypurines hypoxanthine (Hyp), xanthine
      (Xan) and uric acid and the nucleosides guanosine, inosine (Ino) and uridine
      (Urd). RESULTS: Concentrations of Hyp, Xan and Ino were significantly higher in
      the renal than the peripheral vein. The differences between the Xan, Hyp, Ino and
      Urd plasma concentrations in the renal and peripheral veins before and 5 min
      after reperfusion correlated positively and significantly with serum creatinine
      concentrations 24 and 72 h after graft transplantation. Moreover, the
      concentrations of Hyp were significantly increased in renal transplant recipients
      with delayed graft function. CONCLUSION: The results of this study suggest that
      the concentration of Hyp in the kidney allograft vein can be a useful predictor
      of early graft function.

PMID- 17454958
TI  - Urothelial adenocarcinoma in a non-functioning bladder.
AB  - Urinary diversion is a common final outcome in patients with refractory long-term
      incontinence. It is even more common in young patients with neurogenic bladders
      and in such cases the bladder is disconnected and left in situ. We present a
      unique case of adenocarcinoma of the bladder which occurred 31 years following
      such a diversion procedure. We ask whether, despite the comorbidity associated
      with cystectomy, the patient is in danger of developing effectively silent
      tumours within these non-functioning bladders.

PMID- 17454959
TI  - Non-Fournier's gangrene of the penis: Report of two cases and review of the
      literature.
AB  - Dry gangrene of the penis due to ischaemia is a rare condition. In cases
      previously reported in the literature, the aetiology was end-stage renal failure
      in combination with severe arteriosclerosis and diabetes mellitus. We present
      herein two cases of dry gangrene of the penis with two different aetiologies.

PMID- 17454960
TI  - Azathioprine-induced squamous cell carcinoma of the kidney.
AB  - Immunosuppressive therapy with azathioprine has been documented to cause squamous
      cell carcinoma (SCC) at various sites. We report possibly the first case of SCC
      of the kidney in a young male who received azathioprine for a long time.
      Discontinuation of azathioprine post-radical nephrectomy probably increased the
      patient's metastatic disease-free survival.

PMID- 17454961
TI  - Stress milestones.

PMID- 17454962
TI  - GABA(A) receptor neurotransmission dysfunction in a mouse model of social
      isolation-induced stress: possible insights into a non-serotonergic mechanism of
      action of SSRIs in mood and anxiety disorders.
AB  - Protracted social isolation in laboratory animals causes stress, which induces a
      variety of behavioral abnormalities including increased aggressiveness, anxiety
      related behaviors, cognitive deficits and hyper locomotion. Many of these
      disorders are similar to the symptoms found in psychiatric disorders, such as
      depression, anxiety, premenstrual dysphoria and posttraumatic stress disorders
      (PTSD). Recent studies have demonstrated that male mice that have been socially
      isolated for more than 4 weeks show: (a) reduced responsiveness of GABA(A)
      receptors (GABA(A)-R) to the administrations of GABA mimetic drugs at GABA(A)-R;
      (b) downregulated biosynthesis of 3alpha,5alpha-tetrahydroprogesterone
      (3alpha,5alpha-THP) (allopregnanolone: ALLO), a neurosteroid with a potent
      positive allosteric modulatory effect on the action of GABA on GABA(A)-R; and (c)
      alterations in the expression of GABA(A)-R subunits (i.e. a decrease of
      alpha1/alpha2 and gamma2 subunits and an increase of alpha4 and alpha5 subunits).
      The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX) and its
      congener norfluoxetine (Nor-FLX), when administered systemically at nmol/kg
      doses, normalize the reduced content of brain ALLO and the reduced responsiveness
      of GABA(A)-R to GABA mimetic drugs (i.e. pentobarbital) and also attenuate
      aggressive behavior in socially isolated mice in a stereospecific manner.
      Although these compounds inhibit ex vivo serotonin reuptake into brain tissue,
      their SSRI activities require high micromol/kg dose ranges and are not
      stereospecific. These studies suggest that in socially isolated mice,
      abnormalities of GABA(A)-R signal transduction are attributable to the
      downregulation of ALLO production and to a switch in heteropentameric GABA(A)-R
      subunit assembly composition. Hence, the normalization of ALLO biosynthesis may
      be a new target for the development of drugs effective for psychiatric disorders
      related to neurosteroid biosynthesis downregulation.

PMID- 17454963
TI  - The hypothalamo-pituitary-adrenal axis in chronic fatigue syndrome and
      fibromyalgia syndrome.
AB  - The hypothalamo-pituitary-adrenal (HPA) axis plays a major role in the regulation
      of responses to stress. Human stress-related disorders such as chronic fatigue
      syndrome (CFS), fibromyalgia syndrome (FMS), chronic pelvic pain and post
      traumatic stress disorder are characterized by alterations in HPA axis activity.
      However, the role of the HPA axis alterations in these stress-related disorders
      is not clear. Most studies have shown that the HPA axis is underactive in the
      stress-related disorders, but contradictory results have also been reported,
      which may be due to the patients selected for the study, the methods used for the
      investigation of the HPA axis, the stage of the syndrome when the tests have been
      done and the interpretation of the results. There is no structural abnormality in
      the endocrine organs which comprise the HPA axis, thus it seems that
      hypocortisolemia found in the patients with stress-related disorder is
      functional. It may be also an adaptive response of the body to chronic stress. In
      this review, tests used in the assessment of HPA axis function and the HPA axis
      alterations found in CFS and FMS are discussed in detail.

PMID- 17454964
TI  - Differential vascular adaptive response to stress exposure in male and female
      rats: role of gonadal hormones and endothelial cells.
AB  - Although there are reports concerning a vascular adaptive response to stress in
      males, this is not yet defined in females. The aim of this study was to delineate
      functional gender differences in the rat vascular adaptive response to stress and
      to determine the ability of sex hormones to modulate the stress-induced vascular
      adaptive response. Responses to noradrenaline were evaluated in aortas, with and
      without endothelium, from intact, gonadectomized and gonadectomized-hormone
      replaced males and females submitted or not to stress (2-h immobilization).
      Reactivity of the aorta of stressed and non-stressed intact males and females (n
      = 6-14 per group) was also examined in the presence of L-NAME or indomethacin.
      Stress decreased and gonadectomy increased maximal responses to noradrenaline in
      aortas with intact endothelium from both genders. Stress also reduced
      noradrenaline potency in males. In females, but not males, stress decreased the
      gonadectomy-induced noradrenaline hyper-reactivity to near that of intact non
      stressed rats. Hormone replacement restored the gonadectomy-induced impaired
      vascular adaptive response to stress. L-NAME, but not indomethacin, abolished the
      stress-induced decrease in aorta reactivity of males and females. None of the
      procedures altered reactivity of aortas denuded of endothelium. CONCLUSION:
      Stress-induced vascular adaptive responses show gender differences. The magnitude
      of the adaptive response is dependent on testicular hormones and involves
      endothelial nitric oxide-system hyperactivity.

PMID- 17454965
TI  - Loneliness, social support and cardiovascular reactivity to laboratory stress.
AB  - Self-reported or explicit loneliness and social support have been inconsistently
      associated with cardiovascular reactivity (CVR) to stress. The present study
      aimed to adapt an implicit measure of loneliness, and use it alongside the
      measures of explicit loneliness and social support, to investigate their
      correlations with CVR to laboratory stress. Twenty-five female volunteers aged
      between 18 and 39 years completed self-reported measures of loneliness and social
      support, and an Implicit Association Test (IAT) of loneliness. The systolic blood
      pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) reactivity
      indices were measured in response to psychosocial stress induced in the
      laboratory. Functional support indices of social support were significantly
      correlated with CVR reactivity to stress. Interestingly, implicit, but not
      explicit, loneliness was significantly correlated with DBP reactivity after one
      of the stressors. No associations were found between structural support and CVR
      indices. Results are discussed in terms of validity of implicit versus explicit
      measures and possible factors that affect physiological outcomes.

PMID- 17454966
TI  - Cold pressor stress reduces left cradling preference in nulliparous human
      females.
AB  - The left cradling preference refers to the finding that women hold their infants
      more frequently on the left side of their own bodies. Several observational
      studies showed reduced left cradling during stressful circumstances, such as
      mother-infant separation, or domestic violence. However, until now no
      experimental study was conducted to investigate the immediate impact of stress on
      cradling behaviour. Half of the 64 female subjects participating were randomly
      assigned to a stressful bilateral cold pressor test. The remaining subjects
      performed a non-stressful control procedure. Before and after this intervention,
      cradling behaviour was assessed using a baby-like doll. Subjects showed a left
      cradling preference prior to the intervention. The cold pressor test increased
      blood pressure and heart rate significantly. A repeated ANOVA revealed an
      interaction of intervention (cold pressor vs. control) X assessment period (pre-
      vs. post-intervention), indicating that cold pressor stress reduces left cradling
      behaviour in female volunteers. Our data indicate that stress influences cradling
      preference. This may be of relevance for caregiver-infant interactions.

PMID- 17454967
TI  - AMPK alpha subunit gene characterization in Artemia and expression during
      development and in response to stress.
AB  - AMP-activated protein kinase (AMPK) plays a central role in maintaining the
      energy balance of organisms under physiological and environmental stresses. Here
      two AMPK alpha subunit gene transcripts (named Afr-AMPKalpha1 and Afr-AMPKalpha2)
      from Artemia franciscana were isolated and gene expression was characterized by
      semiquantitive reverse transcription-polymerase chain reaction (RT-PCR). Afr
      AMPKalpha1 was differentially expressed during Artemia developmental stages as
      well as in response to stresses, such as heat-shock, starvation and a
      hyperosmotic environment. Afr-AMPKalpha1 mRNA expression in adult Artemia
      decreased under heat shock, but not in a time- and temperature-dependent manner.
      By contrast, the transcript sharply decreased in heat-shocked cysts in a time
      dependent manner. Under hyperosmotic stress, however, the mRNA level in adults
      first declined and then increased with prolonged exposure. In the case of
      starvation, the gene expression in adults decreased and was undetectable after
      day 9. In addition, Afr-AMPKalpha2 mRNA expression was too low to be detected
      without nested PCR. Southern blot analysis, moreover, indicated AMPK alpha
      subunit was present in multiple copies in the Artemia genome. Furthermore, our
      results demonstrate that the Afr-AMPKalpha1 mRNA level sharply decreases in
      Artemia carrying diapause-destined embryos and this indicates the possibility
      that Afr-AMPKalpha1 is involved in determining the reproductive mode in Artemia.

PMID- 17454968
TI  - Exposure to acute physical and psychological stress alters the response of rat
      macrophages to corticosterone, neuropeptide Y and beta-endorphin.
AB  - The objective of the present study was to investigate the effect of acute
      exposure to electric tail shock stress (ES) and a stress witnessing procedure
      (SW), as models for physical and psychological stress paradigms, respectively on
      adherence, phagocytosis and hydrogen peroxide (H(2)O(2)) release from rat
      peritoneal macrophages. In addition, we studied the in vitro effects of
      corticosterone (CORT), neuropeptide Y (NPY) and beta-endorphin (BE) on adherence,
      phagocytosis and H(2)O(2) release from macrophages isolated from control rats and
      from rats that had been exposed to ES or SW procedures 24 h earlier. ES and SW
      comparably diminished phagocytosis and H(2)O(2) release, but did not influence
      macrophage adherence. In vitro treatment with CORT and NPY notably suppressed
      phagocytosis and potentiated H(2)O(2) release from macrophages. BE suppressed
      both phagocytosis and H(2)O(2) release from macrophages. Previous exposure to ES
      and SW altered the responsiveness of the isolated macrophages to their in vitro
      treatment with mediators of stress, making the cells less sensitive to the
      influence of CORT and NPY and to a lesser extent to BE. It could be concluded
      that changes in the local macrophage milieu induced by ES and SW 24 h earlier
      modify macrophage responses to subsequent in vitro exposure to the stress mimics,
      CORT, NPY and BE.

PMID- 17454969
TI  - The limits of 'adaptive' coping: well-being and mood reactions to stressors among
      women in abusive dating relationships.
AB  - Coping is typically thought to be adaptive if it reduces immediate distress and
      promotes well-being. However, coping strategies might appear beneficial in a
      given situation, but when considered in the broader stressor context, those
      situational benefits may actually undermine well-being. Two studies (N = 473 and
      N = 80 women) demonstrated that, in the context of psychologically or physically
      abusive dating relationships, coping orientations were rooted in women's stressor
      history (prior assault trauma) and elevated emotion-focused and lower problem
      focused efforts were predictive of greater depressive symptoms. Yet, in response
      to a stressor video that acted as a reminder of women's abusive experiences (but
      not to a stressor video unrelated to abuse), affective benefits (lower hostility,
      higher positive agency) were associated with abused women's emotion-focused
      coping endorsements, but were not linked to problem-focused coping. It seems that
      in some contexts, reduced distress might limit active efforts to alter a
      dysfunctional situation.

PMID- 17454970
TI  - Lymphocyte subsets, cardiovascular measures and anxiety state before and after a
      professional examination.
AB  - Controversies exist regarding the impact of psychological stress on the
      functioning of the immune system in humans. The aim of the present study,
      therefore, was to evaluate whether the condition of a pre-exam stress may or not
      modify resting lymphocyte subsets, as well as blood pressure and heart rate.
      About 22 medical residents of both sexes not suffering from any medical or
      psychiatric disorder were included in the study. Anxiety levels were measured by
      means of the Hamilton rating scale for anxiety (HRSA) and anxiety traits by means
      of the panic-agoraphobic spectrum self-report (PAS-SR) version and the obsessive
      compulsive spectrum self-report (OBS-SR) version. The results showed that
      systolic blood pressure and heart rate increased significantly just before
      sitting an examination (t(1)) in all subjects, as compared with a calm situation
      (t(2)), in parallel with the increase in the HRSA total score, while no
      significant difference was observed in lymphocyte subsets at the two assessment
      times. However, men had a higher number of CD4+ cells than women at t(1) and
      t(2), while women showed a higher heart rate at t(1). In addition, significant
      correlations between CD4+ lymphocyte count and heart rate at t(1) or HRSA at t(2)
      were detected. These findings indicate that the acute stress determined by
      sitting for examination provokes changes in autonomic nervous system parameters,
      such as blood pressure and heart rate, as well as in the subjective feeling of
      anxiety, as shown by the increased HRSA total scores, which were not paralleled
      by modifications of lymphocyte subsets. However, individual differences, related
      to both sex and personality traits yet to be identified, seem to have an impact
      in shaping the stress response.

PMID- 17454971
TI  - The effects of acute stress and pubertal development on metabolic hormones in the
      rat.
AB  - A dramatic change in stress responsiveness occurs during pubertal development
      such that stress-induced corticosterone secretion in prepubertal animals takes 45
      60 min longer to return to baseline compared to adults. Though corticosterone is
      known to influence energy mobilization, it is presently unknown whether stressors
      affect other hormones important in energy utilization and metabolism
      differentially in animals before and after pubertal development. Therefore, we
      exposed prepubertal (28 days of age) and adult (77 days of age) male rats to a
      single 30 min session of restraint stress in either the light or dark phase of
      the animals' light-dark (LD) cycle and measured plasma glucose, insulin and
      thyroid hormones (thyroxine (T4) and triiodothyronine (T3)). We found similar
      stress-induced increases in plasma glucose levels in prepubertal and adult
      animals in the LD phase of the LD cycle. We also found that prepubertal animals
      have lower circulating insulin and total and free T4 levels, but higher total and
      free T3 levels compared to adults in both the light and dark phases (LD).
      Interestingly, insulin and thyroid hormone levels were unaffected by acute stress
      at either age or time of day. These data indicate that, despite prepubertal
      animals showing an extended glucocorticoid stress response after a single acute
      exposure to stress, glucose levels are similarly affected by acute stress in
      prepubertal and adult animals. Furthermore, though stage of development
      significantly affects the levels of peripheral metabolic hormones such as
      insulin, T4 and T3, acute stress does not appreciably influence their secretion
      before or after puberty.

PMID- 17454972
TI  - Estimation of phylogeny and invariant sites under the general Markov model of
      nucleotide sequence evolution.
AB  - The models of nucleotide substitution used by most maximum likelihood-based
      methods assume that the evolutionary process is stationary, reversible, and
      homogeneous. We present an extension of the Barry and Hartigan model, which can
      be used to estimate parameters by maximum likelihood (ML) when the data contain
      invariant sites and there are violations of the assumptions of stationarity,
      reversibility, and homogeneity. Unlike most ML methods for estimating invariant
      sites, we estimate the nucleotide composition of invariant sites separately from
      that of variable sites. We analyze a bacterial data set where problems due to
      lack of stationarity and homogeneity have been previously well noted and use the
      parametric bootstrap to show that the data are consistent with our general Markov
      model. We also show that estimates of invariant sites obtained using our method
      are fairly accurate when applied to data simulated under the general Markov
      model.

PMID- 17454973
TI  - Widespread genealogical nonmonophyly in species of Pinus subgenus Strobus.
AB  - Phylogenetic relationships among Pinus species from subgenus Strobus remain
      unresolved despite combined efforts based on nrITS and cpDNA. To provide greater
      resolution among these taxa, a 900-bp intron from a late embryogenesis abundant
      (LEA)-like gene (IFG8612)was sequenced from 39 pine species, with two or more
      alleles representing 33 species. Nineteen of 33 species exhibited allelic
      nonmonphyly in the strict consensus tree, and 10 deviated significantly from
      allelic monophyly based on topology incongruence tests. Intraspecific nucleotide
      diversity ranged from 0.0 to 0.0211, and analysis of variance shows that
      nucleotide diversity was strongly associated (P < 0.0001)with the degree of
      species monophyly. Although species nonmonophyly complicates phylogenetic
      interpretations, this nuclear locus offers greater topological support than
      previously observed for cpDNA or nrITS. Lacking evidence for hybridization,
      recombination, or imperfect taxonomy, we feel that incomplete lineage sorting
      remains the best explanation for the polymorphisms shared among species.
      Depending on the species, coalescent expectations indicate that reciprocal
      monophyly will be more likely than paraphyly in 1.71 to 24.0 x 10(6) years, and
      that complete genome-wide coalescence in these species may require up to 76.3 x
      10(6) years. The absence of allelic coalescence is a severe constraint in the
      application of phylogenetic methods in Pinus, and taxa sharing similar life
      history traits with Pinus are likely to show species nonmonophyly using nuclear
      markers.

PMID- 17454974
TI  - Alignment and topological accuracy of the direct optimization approach via POY
      and traditional phylogenetics via ClustalW + PAUP*.
AB  - Direct optimization frameworks for simultaneously estimating alignments and
      phylogenies have recently been developed. One such method, implemented in the
      program POY, is becoming more common for analyses of variable length sequences
      (e.g., analyses using ribosomal genes) and for combined evidence analyses
      (morphology + multiple genes). Simulation of sequences containing insertion and
      deletion events was performed in order to directly compare a widely used method
      of multiple sequence alignment (ClustalW) and subsequent parsimony analysis in
      PAUP* with direct optimization via POY. Data sets were simulated for pectinate,
      balanced, and random tree shapes under different conditions (clocklike, non
      clocklike, and ultrametric). Alignment accuracy scores for the implied alignments
      from POY and the multiple sequence alignments from ClustalW were calculated and
      compared. In almost all cases (99.95%), ClustalW produced more accurate
      alignments than POY-implied alignments, judged by the proportion of correctly
      identified homologous sites. Topological accuracy (distance to the true tree) for
      POY topologies and topologies generated under parsimony in PAUP* from the
      ClustalW alignments were also compared. In 44.94% of the cases, Clustal alignment
      tree reconstructions via PAUP* were more accurate than POY, whereas in 16.71% of
      the cases POY reconstructions were more topologically accurate (38.38% of the
      time they were equally accurate). Comparisons between POY hypothesized alignments
      and the true alignments indicated that, on average, as alignment error increased,
      topological accuracy decreased.

PMID- 17454975
TI  - Is multiple-sequence alignment required for accurate inference of phylogeny?
AB  - The process of inferring phylogenetic trees from molecular sequences almost
      always starts with a multiple alignment of these sequences but can also be based
      on methods that do not involve multiple sequence alignment. Very little is known
      about the accuracy with which such alignment-free methods recover the correct
      phylogeny or about the potential for increasing their accuracy. We conducted a
      large-scale comparison of ten alignment-free methods, among them one new approach
      that does not calculate distances and a faster variant of our pattern-based
      approach; all distance-based alignment-free methods are freely available from
      http://www.bioinformatics.org.au (as Python package decaf+py). We show that most
      methods exhibit a higher overall reconstruction accuracy in the presence of high
      among-site rate variation. Under all conditions that we considered, variants of
      the pattern-based approach were significantly better than the other alignment
      free methods. The new pattern-based variant achieved a speed-up of an order of
      magnitude in the distance calculation step, accompanied by a small loss of tree
      reconstruction accuracy. A method of Bayesian inference from k-mers did not
      improve on classical alignment-free (and distance-based) methods but may still
      offer other advantages due to its Bayesian nature. We found the optimal word
      length k of word-based methods to be stable across various data sets, and we
      provide parameter ranges for two different alphabets. The influence of these
      alphabets was analyzed to reveal a trade-off in reconstruction accuracy between
      long and short branches. We have mapped the phylogenetic accuracy for many
      alignment-free methods, among them several recently introduced ones, and
      increased our understanding of their behavior in response to biologically
      important parameters. In all experiments, the pattern-based approach emerged as
      superior, at the expense of higher resource consumption. Nonetheless, no
      alignment-free method that we examined recovers the correct phylogeny as
      accurately as does an approach based on maximum-likelihood distance estimates of
      multiply aligned sequences.

PMID- 17454976
TI  - Cultural biases and scientific squabbles: the challenges to acceptance of
      testosterone therapy as a mainstream medical treatment.

PMID- 17454977
TI  - Metabolic syndrome and the older male population.

PMID- 17454978
TI  - Prevalence of low forearm bone mineral density in Bulgarian men: a pilot study.
AB  - OBJECTIVE: To determine the prevalence of osteoporosis at the distal forearm in a
      male cohort referred for bone density testing and to compare it to published data
      of Bulgarian women. DESIGN AND SUBJECTS: 315 consecutive Bulgarian men aged 20 to
      84 years were included (mean age 53.74 +/- 14.67 years). 59% of them were self
      referrals. The comparative female group consisted of 8869 Bulgarian women whose
      forearm bone mineral density (BMD) was measured in another study. MEASUREMENTS:
      BMD was measured by single X-ray absorptiometry at the distal forearm (distal and
      ultradistal sites) in all men. T-scores were calculated from manufacturer
      provided Danish male reference data. RESULTS: The ratio of female to male
      patients was 28.2 (8869 to 315). Peak BMD was observed in men aged 30 to 39
      years: 0.560 +/- 0.065 g/cm(2) (distal site) and 0.490 +/- 0.070 g/cm(2)
      (ultradistal site). A steady BMD decline followed reaching 0.492 +/- 0.064
      g/cm(2) at the distal and 0.412 +/- 0.069 g/cm(2) at the ultradistal site in age
      group >70. Age had a rather weak negative impact on forearm BMD described by a
      linear model. In men aged over 50 years the prevalence of osteoporosis at the
      distal site was 21.19%, compared to 20.45% in women. Low bone mass was seen in
      48.77% of men and 32.50% of women. Normal BMD was more frequent in women (47.05%)
      than in men (30.04%). CONCLUSIONS: We found a high prevalence of forearm
      osteoporosis in Bulgarian men which is comparable to that already known in women.

PMID- 17454979
TI  - Gonadal steroids and visuo-spatial abilities in adult males: implications for
      generalized age-related cognitive decline.
AB  - The relationship between the gonadal steroids, testosterone and estrogen, and
      individual and group differences in performance on some cognitive tasks remains
      unclear but sex differences favoring males on some tests of visuo-spatial ability
      are large and robust. This aim of this review is to assess evidence for both
      organizational and activational effects of gonadal steroids as the principle
      cause of sex difference in visuo-spatial ability. Additionally, the implications
      of this relationship are discussed in the context of decreasing levels of gonadal
      steroids in aging males and psychological theories of generalized age-related
      cognitive decline. Based upon human and non-human research gonadal steroids have
      organizational effects on visuo-spatial ability in adulthood. Activational
      effects of gonadal steroids on visuo-spatial ability appear most dominant in
      older men and are necessary for maintaining optimal visuo-spatial ability;
      randomized clinical trials show that testosterone supplementation improves
      performance. Additionally, decreasing gonadal steroid levels in aging males may
      contribute to generalized age-related cognitive decline. Future supplementation
      studies in men should attempt to control for constituent abilities related to
      visuo-spatial task performance, and investigate interactions between dosage
      levels and baseline gonadal status. Further future animal research is required to
      investigate changes in gonadal steroid levels and their relationship to
      neurotransmitter systems, neural plasticity, and behavioral correlates.

PMID- 17454981
TI  - Ethics and public health emergencies: encouraging responsibility.
AB  - The three primary ethical challenges in preparing for public health emergencies -
      addressing questions of rationing, restrictions and responsibilities - all entail
      confronting uncertainty. But the third, considering whether people and
      institutions will live up to their responsibilities in a crisis, is perhaps the
      hardest to predict and therefore plan for. The quintessential example of a
      responsibility during a public health emergency is that of health care
      professionals' obligation to continue caring for patients during epidemics.
      Historically, this 'duty to treat' has sometimes gone unrecognized or ignored,
      but it has also famously been adhered to, including during the recent SARS
      epidemic. And non-crisis examples of health professionals working in the face of
      personal risk are very common. The duty to treat should be circumscribed by
      several considerations, including the levels or risk and benefit at issue, the
      degree of public reliance on health professional action, and the nature of the
      individual health professional's acceptance of greater than usual risk. Examining
      the professional duty to treat and the legitimate questions it raises can provide
      insight into other actors' responsibilities. Public health ethics as well as
      professional ethics can help frame answers to some key questions: How strong are
      ethical responsibilities during crises? To whom do they apply? Should they be
      more explicit - and hence more circumscribed - or less explicit and hence largely
      aspirational? And how can public health policies encourage responsible actions?

PMID- 17454984
TI  - Medical ethics and the interrogation of Guantanamo 063.
AB  - The controversy over abusive interrogations of prisoners during the war against
      terrorism spotlights the need for clear ethics norms requiring physicians and
      other clinicians to prevent the mistreatment of prisoners. Although policies and
      general descriptions pertaining to clinical oversight of interrogations in United
      States' war on terror prisons have come to light, there are few public records
      detailing the clinical oversight of an interrogation. A complaint by the Federal
      Bureau of Investigation (FBI) led to an Army investigation of an interrogation at
      the United States prison at Guantanamo Bay. The declassified Army investigation
      and the corresponding interrogation log show clinical supervision, monitoring and
      treatment during an interrogation that employed dogs, prolonged sleep
      deprivation, humiliation, restraint, hypothermia and compulsory intravenous
      infusions. The interrogation and the involvement of a psychologist, physician and
      medics violate international and medical norms for the treatment of prisoners.

PMID- 17454986
TI  - Gunther von Hagens' BODY WORLDS: selling beautiful education.
AB  - In the BODY WORLDS exhibitions currently touring the United States, Gunther von
      Hagens displays human cadavers preserved through plastination. Whole bodies are
      playfully posed and exposed to educate the public. However, the educational aims
      are ambiguous, and some aspects of the exhibit violate human dignity. In
      particular, the signature cards attached to the whole-body plastinates that bear
      the title, the signature of Gunther von Hagens, and the date of creation mark the
      plastinates as artwork and von Hagens as the artist in a gesture that strips the
      personal dignity from the donors. I conclude that the educational use of cadavers
      is compatible with respect for dignity if: 1) the utility of such use is great
      enough; 2) there are no other ways of achieving these ends; and 3) every effort
      is made to honor the dignity of the donors.

PMID- 17454987
TI  - No dignity in BODY WORLDS: a silent minority speaks.

PMID- 17454988
TI  - BODY WORLDS as education and humanism.

PMID- 17454989
TI  - The tenuous world of plastinates.

PMID- 17454990
TI  - Metamorphosis: beautiful education to smarmy edutainment.

PMID- 17454991
TI  - The virtues of blurring boundaries in BODY WORLDS.

PMID- 17454992
TI  - Taking public education seriously: BODY WORLDS, the science museum, and
      democratizing bioethics education.

PMID- 17454993
TI  - Responsibility and provenance of human remains.

PMID- 17454994
TI  - BODY WORLDS: choosing to be immortalized as an educational specimen.

PMID- 17454995
TI  - A visual anthropological approach to the "edutainment" of BODY WORLDS.

PMID- 17454996
TI  - The stakes are not very high in this game.

PMID- 17454997
TI  - The abstract nature of anatomic construction and its advantages: scientific
      medicine and human dignity.

PMID- 17454998
TI  - Awesome and captivating, but is it really educational?

PMID- 17454999
TI  - Would we rather lose our life than lose our self? Lessons from the Dutch debate
      on euthanasia for patients with dementia.
AB  - This article reviews the Dutch societal debate on euthanasia/assisted suicide in
      dementia cases, specifically Alzheimer's disease. It discusses the ethical and
      practical dilemmas created by euthanasia requests in advance directives and the
      related inconsistencies in the Dutch legal regulations regarding
      euthanasia/assisted suicide. After an initial focus on euthanasia in advanced
      dementia, the actual debate concentrates on making euthanasia/assisted suicide
      possible in the very early stages of dementia. A review of the few known cases of
      assisted suicide of people with so-called early dementia raises the question why
      requests for euthanasia/assisted suicide from patients in the early stage of
      (late onset) Alzheimer's disease are virtually non-existent. In response to this
      question two explanations are offered. It is concluded that, in addition to a
      moral discussion on the limits of anticipatory choices, there is an urgent need
      to develop research into the patient's perspective with regard to medical
      treatment and care-giving in dementia, including end-of-life care.

PMID- 17455000
TI  - The view from before.

PMID- 17455001
TI  - Right question, but not quite the right answer: whether there is a third
      alternative in choices about euthanasia in Alzheimer's disease.

PMID- 17455002
TI  - Help! My body is being invaded by an alien!

PMID- 17455003
TI  - What makes suffering "unbearable and hopeless"? Advance directives, dementia and
      disability.

PMID- 17455004
TI  - Conflicting preferences and advance directives.

PMID- 17455005
TI  - An Islamic perspective on euthanasia.

PMID- 17455006
TI  - The study of socioethical issues in systems biology.
AB  - Systems biology is the rapidly growing and heavily funded successor science to
      genomics. Its mission is to integrate extensive bodies of molecular data into a
      detailed mathematical understanding of all life processes, with an ultimate view
      to their prediction and control. Despite its high profile and widespread
      practice, there has so far been almost no bioethical attention paid to systems
      biology and its potential social consequences. We outline some of systems
      biology's most important socioethical issues by contrasting the concept of
      systems as dynamic processes against the common static interpretation of genomes.
      New issues arise around systems biology's capacities for in silico testing,
      changing cultural understandings of life, synthetic biology, and
      commercialization. We advocate an interdisciplinary and interactive approach that
      integrates social and philosophical analysis and engages closely with the
      science. Overall, we argue that systems biology socioethics could stimulate new
      ways of thinking about socioethical studies of life sciences.

PMID- 17455007
TI  - The relation of ethics and science: a commentary on "The study of socioethical
      issues in systems biology".

PMID- 17455008
TI  - Systems bioethics.

PMID- 17455009
TI  - Enough about rawls already: systems theory and bioethics in the 21st century.

PMID- 17455010
TI  - Everything old is new again, including systems biology.

PMID- 17455011
TI  - From describing to performing the socioethical engagement with systems biology.

PMID- 17455014
TI  - American Academy of Clinical Neuropsychology (AACN) practice guidelines for
      neuropsychological assessment and consultation.
AB  - This document is the first set of practice guidelines to be formally reviewed and
      endorsed by the AACN Board of Directors and published in the official journal of
      AACN. They have been formulated with the assumption that guidelines and standards
      for neuropsychological assessment and consultation are essential to professional
      development. As such, they are intended to facilitate the continued systematic
      growth of the profession of clinical neuropsychology, and to help assure a high
      level of professional practice. These guidelines are offered to serve members of
      AACN, as well as the field of clinical neuropsychology as a whole.

PMID- 17455015
TI  - Disclosure of neuropsychological test data: official position of Division 40
      (Clinical Neuropsychology) of the American Psychological Association, Association
      of Postdoctoral Programs in Clinical Neuropsychology, and American Academy of
      Clinical Neuropsychology.

PMID- 17455016
TI  - Predictors of subjective well-being among individuals with multiple sclerosis.
AB  - Neuropsychological and psychosocial predictors of subjective well-being (SWB)
      were examined among 74 persons with multiple sclerosis (MS). The multidimensional
      construct of SWB was assessed by self-report measures of acute psychological
      distress, global life satisfaction, and health-related quality of life (HRQoL).
      Objective disease-related indices were obtained from medical records and
      neuropsychological testing. Unawareness of deficit, a frequent aspect of
      executive function impairments in MS, was measured as the discrepancy between
      patient self-report of functional abilities and a caregiver's report of the
      patient's abilities. Results indicate that a substantial proportion of patients
      experienced diminished SWB and that disease characteristics such as duration and
      severity have differential relationships to SWB outcomes. Multiple regression
      analyses indicated that, in the context of a combined predictive model, social
      support and unawareness of deficit provided unique information in predicting all
      three aspects of SWB, beyond that accounted for by disease characteristics. Both
      social support and unawareness of deficit were associated with positive well
      being outcomes. Neuropsychological impairment was adversely related to life
      satisfaction and HRQoL, but it did not add unique information to the prediction
      of these outcomes. The findings present a unique view of SWB among individuals
      with MS in the absence of acute exacerbation of the illness.

PMID- 17455017
TI  - Patient and family perceptions of the neuropsychological evaluation: how are we
      doing?
AB  - To assess perceptions of the neuropsychological evaluation, 349 patients and 218
      significant others presenting to an academic medical center neuropsychology
      service were surveyed over a two year period. Thirty-seven percent of the patient
      surveys (n = 129) and 37% of the significant other surveys (n = 80) were
      returned. Overall, both patients and significant others reported being satisfied
      with the interview, testing, and feedback sessions. Responders were generally
      receptive to the recommendations made, but were more inclined to have followed
      recommendations regarding patient safety (63.6%) than coping or support (31.8%).
      Some barriers to compliance with recommendations were identified.

PMID- 17455018
TI  - Executive control functioning and functional ability in older adults.
AB  - The manner in which executive control functioning exerts its influence on
      functional tasks was investigated. Sixty older adults were administered
      neuropsychological tasks tapping into four domains of executive control function,
      including working memory, planning, fluency, and flexibility. A test of
      performance-based functional ability also was administered. Correlational
      analyses demonstrated that working memory was most strongly associated with
      performance-based functional ability; however, impairment in planning appeared to
      best predict performance-based functional decrement in simultaneous regression
      models. Results highlight the role of planning in the maintenance of functional
      ability, as measured by performance-based functional measures.

PMID- 17455019
TI  - Construct validity of the Repeatable Battery of Neuropsychological Status (RBANS)
      with acquired brain injury patients.
AB  - The construct validity of the Repeatable Battery for the Assessment of
      Neuropsychological Status (RBANS) indices and subtests in comparison to
      established neuropsychological measures has yet to be investigated in post-acute
      adults with a moderate to severe acquired brain injury. A sample of 37 patients
      from an inpatient brain injury rehabilitation program were administered the RBANS
      followed by a neuropsychological test battery approximately two weeks later.
      Significant relationships were observed between most of the RBANS subtests and
      indices and neuropsychological tests putatively assessing similar cognitive
      domains. These results provide preliminary support for the construct validity of
      the RBANS indices and subtests when used with moderate to severe acquired brain
      injury patients.

PMID- 17455020
TI  - Developing clinically suitable measures of social cognition for children: initial
      findings from a normative sample.
AB  - Our understanding of children's social competence has increased tremendously over
      the past two decades. There is increasing evidence to suggest that social
      cognitive impairments are not restricted to children on the autistic spectrum,
      but rather may be associated with a host of developmental and acquired
      neurological conditions including learning disabilities, attention deficit
      disorder, traumatic brain injury, and stroke. Although many investigators have
      begun to bridge the gap between clinical practice and research by applying
      experimental tasks to clinical populations, few tools are available for the
      clinical evaluation of social competence, particularly in children. This study
      marks a series of first steps in the development of measures suitable for the
      assessment of children between 6 and 12 years of age. The results of the study
      provide data for a number of experimental tasks that have been adapted with
      clinical practice in mind. A discussion of the developmental progressions and the
      relationships among the measures is also included.

PMID- 17455021
TI  - The Booklet Category Test and malingering in traumatic brain injury:
      classification accuracy in known groups.
AB  - A known-groups design was used to determine the classification accuracy of 12
      Booklet Category Test variables in the detection of malingered neurocognitive
      dysfunction (MND) in traumatic brain injury (TBI). Participants were 206 TBI and
      60 general clinical patients seen for neuropsychological evaluation. Slick,
      Sherman, and Iverson's (1999) criteria were used to classify the TBI patients
      into non-malingering, suspect, and MND groups. Classification accuracy of the BCT
      depended on the specific variable and injury severity examined, with some scores
      detecting more than 40% of malingerers with false positive error rates of 10% or
      less. However, the BCT variables are often influenced by cognitive ability as
      well as malingering, so caution is indicated in applying the BCT to the diagnosis
      of malingering. Application of these data in clinical practice is discussed.

PMID- 17455022
TI  - Neuropsychological outcomes of preterm triplets discordant for birthweight: a
      case report.
AB  - Multiple gestation is associated with a higher incidence of preterm birth and
      preterm birth often results in later neurocognitive and behavioral problems that
      persist into adulthood. The medical, neurobiological, familial, and socio
      environmental factors determinant for an individual are unpredictable. We present
      neuropsychological data for fraternal triplets discordant for birthweight whose
      school-age outcome was inconsistent with the low birthweight literature and for
      whom neurobiological variables appeared especially pertinent. Preterm infants may
      achieve optimal outcomes, although etiological factors leading to such outcomes
      may depend heavily on care center variables that limit or avoid intracerebral and
      other medical complications of prematurity.

PMID- 17455028
TI  - Comparative utility of Barona Formulae, Wtar demographic algorithms, and WRAT-3
      reading for estimating premorbid ability in a diverse research sample.
AB  - Various Barona formulae, a WTAR algorithm based on demographic data, and WRAT-3
      oral reading methods of estimating premorbid ability were compared in a diverse
      research sample of 119 subjects. These methods were correlated with one another
      and with a modified version of the Raven Standard Progressive Matrices.
      Descriptive data are provided to illustrate advantages and disadvantages of
      various methods of estimating premorbid ability when no formal intellectual
      testing is available. While predicting premorbid ability for individual subjects
      involves varying degrees of error, we found that the revised Barona formula was
      superior to the original formula for subjects at the upper end of ability level.
      When researchers have screened out learning disability and have subject samples
      with few individuals likely to be of superior premorbid intelligence, oral
      reading scores are a reasonable measure of premorbid ability. Otherwise,
      researchers are advised to use both demographic and oral reading methods to
      estimate premorbid ability.

PMID- 17455029
TI  - Clinical validation of Canadian WAIS-III Index short forms in inpatient
      neuropsychiatry and forensic psychiatry.
AB  - Recent research has provided some support for the concurrent validity of two
      subtest short forms for estimating Canadian WAIS-III Index scores in the
      standardization sample (Lange & Iverson, in press). The purpose of this study was
      to examine the efficacy of using various two-subtest short forms to estimate
      Canadian WAIS-III Index scores in a clinical population. Participants were 100
      inpatients from two large psychiatric hospitals in British Columbia, Canada.
      Using all possible two-subtest combinations, estimated VCI, POI, and WMI scores
      were generated by prorating subtest scaled scores and using the Canadian
      normative data (Wechsler, 2001). The agreement rate between full form and short
      form index scores was very high for all subtest combinations (range = 90-98%).
      Two-subtest short forms were useful for estimating VCI, POI, and WMI scores in
      this population.

PMID- 17455030
TI  - The prevalence of seizure types among individuals referred for phase I
      neuropsychological assessment: demographic and neuropsychological
      characteristics.
AB  - The prevalence of seizure types among the subpopulation of patients referred for
      phase I neuropsychological assessment likely differs from the prevalence of
      specific seizure types within the general seizure population. Understanding the
      prevalence of clinical diagnoses is critical to maximizing the predictive value
      of any assessment or diagnostic technique, clinical neuropsychological assessment
      of patients with seizures being no exception. Data from a series of 835 patients
      referred for phase I neuropsychological evaluation are used to report the
      prevalence of specific seizure types, as well as neuropsychological and
      demographic characteristics. Considerations for clinical neuropsychological
      research and practice are briefly discussed.

PMID- 17455031
TI  - Modified Wisconsin Card Sorting Test (MCST, MWCST): normative data in children 4
      13 years old, according to classical and new types of scoring.
AB  - According to Nelson's (1976) criteria, the MCST (MWCST) is a simplification of
      the Wisconsin Card Sorting Test (WCST). As the MCST is particularly suitable for
      children, the aim of this study was to establish the normative data presently
      lacking for that group. The MCST was administered to 1126 normal children aged 4
      to 13 years. Scoring was based on all the classical parameters, according to
      existing criteria, plus two new ones that we propose ("categorizing efficiency"
      and "categorizing efficiency plus"). Strong correlation (or inverse correlation)
      with age is found for most parameters, including all criteria used for
      perseverative responses. This does not occur for "failure to maintain set,"
      calculated according to the usual criteria. "Categorizing efficiency" and
      "categorizing efficiency plus" avoid the ceiling effect occurring at higher ages
      in the parameter categories. The MCST may be used in children 4 years of age and
      above. Most, but not all, of its parameters show regular improvement with age,
      demonstrating their validity. However, our data suggest that a participant's
      performance on the MCST may be based essentially on two parameters: categorizing
      efficiency (or categorizing efficiency plus), measuring the participant's ability
      to categorize, and perseverative errors (or percent perseverative errors),
      measuring his or her difficulty in shifting, both considered typical executive
      functions.

PMID- 17455032
TI  - Clinical assessment of hemispatial neglect: evaluation of different measures and
      dimensions.
AB  - The multidimensional nature of the neglect syndrome constitutes a challenge for
      clinical assessments. This study evaluates the sensitivity of different clinical
      measures to detect neglect and explores ways to evaluate the diversity of the
      syndrome in a clinical sample. An extensive battery of tests was used to examine
      aspects of visuospatial, representational, and personal neglect. A total of 31
      normal control participants and 34 patients with right hemisphere stroke were
      examined 16.8 days post-stroke, on average. Of the patients, 24 showed neglect in
      at least one task. The Random shape cancellation test, Star cancellation, and two
      line bisection tasks appeared to be the most sensitive tests of visuospatial
      neglect. Personal neglect and neglect in far space occurred only together with
      extrapersonal neglect. Besides near space, other spatial aspects of neglect are
      important to consider in clinical assessments, but standardized methods are
      needed. In this patient group a minimum of 10 tests were needed to cover various
      aspects of detection, dissociations, and severity of neglect. A multifactorial
      approach in clinical testing of neglect is recommended.

PMID- 17455033
TI  - Relation between cognitive testing performance and pattern of substance use in
      males at treatment entry.
AB  - This study examined the frequency and pattern of cognitive impairment in
      individuals entering substance use disorder treatment and additionally examined
      the relation between pattern of cognitive impairment and type of substance(s)
      used: alcohol (n = 116), cocaine (n = 49), alcohol/cocaine (n = 76), and
      alcohol/multiple substance (n = 54). The Cognistat, a screening measure of
      cognitive functioning, and the Addiction Severity Index were given to male
      veterans at the time of entering 3- to 4-week residential/day drug treatment. The
      most prominent areas of impairment were memory (37% of the total sample) and
      similarities or abstract concept formation (21% of the total sample). Moderate or
      greater severity of impairment was noted on at least one Cognistat scale in 35%
      of the participants. Results indicated no significant differences in the patterns
      of cognitive domain impairment between groups based on type(s) of substances used
      at the time of entering treatment. Multiple substance use was significantly
      related to greater levels of psychiatric problems as identified by the Alcohol
      Severity Index. Given the rate of impairment in memory and verbal abstract
      reasoning noted, it is suggested that cognitive screening be a standard
      consideration in residential substance use disorder treatment to assist in
      treatment selection and delivery that is optimized to provide maximal benefit to
      patients.

PMID- 17455034
TI  - Test of memory malingering (TOMM) trial 1 as a screening measure for insufficient
      effort.
AB  - The identification of insufficient effort is critical to neuropsychological
      evaluation, and several existing instruments assess effort on neuropsychological
      tasks. Yet instruments designed to detect insufficient effort are underutilized
      in standard neuropsychological assessments, perhaps in part because they
      typically require significant administration time and are, therefore, not ideally
      suited to screening contexts. The Test of Memory Malingering (TOMM) is a commonly
      administered, well-validated symptom validity test. This study evaluates the
      utility of TOMM Trial 1 as a relatively brief screening measure of insufficient
      effort. Results suggest that TOMM Trial 1 demonstrates high diagnostic accuracy
      and is a viable option for screening insufficient effort. Diagnostic accuracy
      estimates are presented for a range of base rates. The need for more
      comprehensive SVT assessment in most clinical and forensic situation is
      discussed.

PMID- 17455035
TI  - Victoria Symptom Validity Test performance in a heterogenous clinical sample.
AB  - We retrospectively reviewed Victoria Symptom Validity Test (VSVT) in 374 patients
      who underwent neuropsychological assessment in an academic hospital-based
      practice. Patients were classified as either non-TBI clinically referred
      (generally patients referred from neurology, neurosurgery, or medicine),
      clinically referred TBI (no known external financial incentive), and non-clinical
      referrals (e.g., attorney-referred, Worker's Compensation). Three patients were
      not classified into any group and considered separately. Intentional response
      distortion, defined as statistically less than chance performance on hard VST
      items, was present in only 1/306 (0.3%) clinically referred non-TBI patients, and
      no clinically referred TBI patient obtained scores significantly less than chance
      on this measure. One additional clinically referred patient with a non-neurologic
      diagnosis who was subsequently found to be pursuing a disability claim also
      performed worse than chance. In contrast, 5/25 patients (20%) referred by
      attorneys or otherwise deemed a priori to be at-risk for deficit exaggeration
      performed less than chance. These data suggest that intentional response
      distortion in patients referred for non-forensic neuropsychological evaluation is
      rare. Performances by specific diagnosis using different classification criteria
      are also presented.

PMID- 17455036
TI  - Test of Memory Malingering (TOMM) scores are not affected by chronic pain or
      depression in patients with fibromyalgia.
AB  - Neuropsychologists routinely give effort tests, such as the Test of Memory
      Malingering (TOMM). When a person fails one of these tests, the clinician must
      try to determine whether the poor performance was due to suboptimal effort or to
      chronic pain, depression, or other problems. Participants were 54 community
      dwelling patients who met American College of Rheumatology criteria for
      fibromyalgia (FM). In addition to the TOMM, they completed the Beck Depression
      Inventory-Second Edition, Multidimensional Pain Inventory-Version 1, Oswestry
      Disability Index-2.0, British Columbia Cognitive Complaints Inventory, and the
      Fibromyalgia Impact Questionnaire. The majority endorsed at least mild levels of
      depressive symptoms (72%), and 22% endorsed "severe" levels of depression. The
      average scores on the TOMM were 48.8 (SD = 1.9, range = 40-50) for Trial 1, 49.8
      (SD = 0.5, range = 48-50) for Trial 2, and 49.6 (SD = 0.9, range = 45-50) for
      Retention. Despite relatively high levels of self-reported depression, chronic
      pain, and disability, not a single patient failed the TOMM. In this study, the
      TOMM was not affected by chronic pain, depression, or both.

PMID- 17455037
TI  - Intrauterine contraception: an under-utilized method of family planning.

PMID- 17455038
TI  - Contraception: a social revolution.
AB  - Modern contraceptive technology is more than a technical advance: it has brought
      about a true social revolution, the 'first reproductive revolution' in the
      history of mankind. This latter was followed in rapid succession by other major
      changes in human reproductive strategies. In the human species, sexual activity
      began to lose its exclusive reproductive meaning at an early stage of its
      evolution. Human beings must have practiced non-conceptive sex from the outset
      and therefore must have had a need to avoid, rather than to seek conception
      during intercourse from time immemorial. The search for methods to control
      fertility went on for millennia, but a valid solution was only found during the
      twentieth century, when the population explosion had forever changed the shape of
      humanity: in only one century the total population of the planet had grown from
      some 1.6 billion to more than 6 billion. That increase will remain unique in the
      history of Homo sapiens. At the global level, contraception provided a tool to
      deal with overpopulation and, in only 50 years, went a long way towards its
      resolution. However, to solve the problem, national and international family
      planning initiatives were required. For individuals, contraception also meant a
      revolution. It allowed sexual intercourse without reproduction. Only 25 years
      later, in vitro fertilisation permitted childbearing without sexual intercourse.
      Other advances followed and now cloning, that is, reproduction without the two
      gametes, looms on the horizon. Such a series of rapid, major changes in human
      reproductive strategies has confused many. For this reason, a constructive
      dialogue between sociology and biology is mandatory. Contraception is a powerful
      tool to promote equity between sexes; it improves women's status in the family
      and in the community. Avoiding pregnancy during the teens increases opportunities
      for a young woman's education, training and employment. By controlling their
      fertility, women get a chance to contribute economically to their household,
      which in turn may give them a greater share in decision-making. There are other
      specific areas in which contraception has produced beneficial social effects,
      first and foremost in reducing the need for induced abortion. It has also helped
      avoiding sexually-transmitted infections and is a very useful tool for educating
      youngsters to adopt more responsible sexual behaviors. Interventions in the field
      of family planning are among the most cost-effective health interventions.

PMID- 17455039
TI  - Contraceptive counseling for orthodox Jewish women.
AB  - OBJECTIVES: The evaluation of birth control issues among orthodox Jews who
      strictly follow the Halachah (the Jewish codes of conduct). METHODS: We examine
      traditional Jewish concepts and practices of reproduction, review various
      contraceptive methods, and define problems that may arise with their use in the
      Jewish orthodox society. We focus on the orthodox and ultra-orthodox (Haredi)
      elements of the Jewish community. RESULTS: The choices of orthodox religious
      women are limited and determined largely by considerations related to religious
      doctrine. CONCLUSIONS: Understanding the religious, social and cultural
      background of patients, religious orthodox women in particular, enables to
      appropriately counsel them.

PMID- 17455040
TI  - Outcome of vasectomies performed at a Turkish metropolitan maternity hospital.
AB  - OBJECTIVE: To determine prospectively the outcome of vasectomies performed by two
      trained surgeons over a 9-month period at the Ministry of Health Ankara Etlik
      Maternity and Women's Health Teaching and Research Hospital Family Planning
      Centre. METHODS: The demographic data, source of information concerning the
      method, sexual function before and after voluntary no-scalpel vasectomy,
      compliance with the post-vasectomy follow-up program of men applying for a
      vasectomy were analyzed. All patients were contacted by telephone and invited for
      follow-up visits for counseling, inquiry regarding sexual dysfunction, and
      performance of a semen analysis. RESULTS: The patients were married men, mostly
      primary school graduates, with more than one child. Sources of information were
      health services and/or health personnel for 89% of the patients. Of the 279 men
      who underwent a vasectomy and who were later contacted by phone, 131 (47%) came
      for a follow-up assessment. There was only one post-vasectomy pregnancy (0.8%).
      The incidence of reported sexual problems did not change after the procedure.
      Vasectomy did not affect the sexual function of men in our study. CONCLUSION:
      Compliance with follow-up after vasectomy, which is extremely important for
      assessment of its successful outcome, is low.

PMID- 17455041
TI  - Comparison of diaphragm and combined oral contraceptive pill users in the
      Australian family planning setting.
AB  - OBJECTIVES: To determine the number of women fitted with a diaphragm or cervical
      cap at family planning clinics across the Australian State of New South Wales
      (NSW) from 2000 to 2005. To compare the demographic characteristics of women
      fitted with this form of contraceptive with women prescribed the combined oral
      contraceptive pill (COCP). METHOD: An audit of women presenting for contraceptive
      services between 2000 and 2005 was undertaken. The demographic characteristics of
      women fitted with a barrier method or prescribed the COCP between 1st April,
      2002, and 31st October, 2004, were obtained from the Family Planning NSW Activity
      Data Set (FADS). RESULTS: The proportion of women fitted with a diaphragm or cap
      remained constant between 2001 and 2005 at approximately 5%. During the 31 months
      that the study period lasted, 793 women were fitted with a diaphragm or cervical
      cap compared with 8047 women prescribed the COCP during the same time frame
      (including 76 women who received both a diaphragm and COCP prescription during
      this period). Women fitted with the barrier contraceptive were significantly more
      likely to be older, to have received a tertiary level education and to have
      private health insurance than their counterparts prescribed the COCP. They were
      less likely to come from a non-English speaking background. DISCUSSION: The
      diaphragm and cervical cap are viable contraceptive methods for a specific group
      of older, well-educated women. The possible benefits of female-controlled barrier
      devices in the prevention of sexually transmissible infections may result in a
      wider demographic use in the future.

PMID- 17455042
TI  - Efficacy of an oral contraceptive containing drospirenone in the treatment of
      women with polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate the efficacy of a combined oral contraceptive
      containing 30 microg ethinyloestradiol and 3 mg drospirenone in the treatment of
      hyperandrogenism affecting women with the polycystic ovary syndrome (PCOS).
      METHODS: Prospective open study of 20 women for six cycles. At the beginning and
      at the end of the study the following values were determined: the Ferriman
      Gallwey (F-G) score, body mass index, waist/hip ratio, serum levels of
      testosterone, SHBG, immune reactive insulin (IRI), glucose, the free androgenic
      index, and insulin resistance (HOMA-IR). RESULTS: All 20 women completed six
      cycles of therapy. The medication was well tolerated. At the end of the study
      there was a significant improvement of hirsutism, expressed in the decrease of
      the F-G score, accompanied by a decrease of testosterone and an increase of SHBG
      values. The carbohydrate metabolism was not affected significantly. CONCLUSION:
      The combined oral contraceptive containing 30 microg ethinyloestradiol and 3 mg
      drospirenone is an effective drug in the treatment of hyperandrogenism in women
      with PCOS; it elicits few side effects and does not significantly influence
      insulin resistance.

PMID- 17455043
TI  - Predictors and confounders of unprotected sex: a UK web-based study.
AB  - OBJECTIVES: To evaluate the effects of gender, sex orientation, age, relationship
      status, age at first sex education, age at first sex, frequency of sex and number
      of sexual partners on the likelihood of unprotected sex in the United Kingdom
      (UK). METHODS: A web-based survey was conducted in the UK in 2004 with 10,138
      respondents. Eight variables were chosen as potential predictors of unprotected
      sex. Responses from sexually active participants were combined and crude/adjusted
      odds ratios (AORs) were calculated for binary/categorical variables. RESULTS: No
      differences were found in AOR for gender, sex orientation, relationship status
      and frequency of sex. Differences were found in AOR for age, sex education, age
      at first sex and number of sexual partners, e.g. AOR 21-24 years of age versus
      under 16 (1.92, CI 1.38-2.68; p-value < 0.001); AOR sex education never received
      versus first sex education under 10 years of age (1.45, CI 1.12-1.87; p-value <
      0.01); AOR first sex at 20 years versus at 14 years (0.56, CI 0.40-0.79; p-value
      < 0.01); and AOR 11-20 partners versus one partner (24.91, CI 20.02-30.98; p
      value < 0.001). The association of sex orientation and relationship status with
      unprotected sex is confounded by the number of sexual partners. CONCLUSIONS: UK
      health and education authorities should develop strategies to provide sex
      education starting in primary school and continuing throughout secondary school.
      Prevention programs and policies should focus on particular sexual behaviours.
      Furthermore, an understanding of sexual diversity and reducing stigmatisation of
      sexual orientation is necessary.

PMID- 17455044
TI  - Use of contraceptive methods and risk of unwanted pregnancy in Spanish women aged
      40-50 years: results of a survey conducted in Spain.
AB  - A survey intended to ascertain the rate of use and type of contraceptive methods
      applied by Spanish women aged 40 to 50 years, and to determine the proportion of
      women in this group at risk of an unwanted pregnancy, was designed and validated.
      To achieve representative national results for the study population, it was
      estimated that a sample size of 2000 women was required. Women were selected
      using probabilistic, stratified random sampling. The survey questionnaire was
      prepared by the research group with the collaboration of experts in the conduct
      of population studies of this type. Participants were interviewed face to face by
      qualified and trained staff from a specialised company external to the research
      group. Overall, 1039 women (52%) resorted to some contraceptive method, of which
      (male or female) sterilisation was the most common. We estimate that in Spain
      there are 840,000 women (31.8%) aged 40 to 50 years at risk of unwanted
      pregnancy.

PMID- 17455045
TI  - Difficulties in adaptation to pregnancy following natural conception or use of
      assisted reproduction techniques: a comparative study.
AB  - BACKGROUND: To evaluate the influence assisted reproduction techniques (ARTs) may
      have on women's adaptation to resulting pregnancies. METHODS: Retrospective
      assessment of how women adapt to their pregnancies following ART. A questionnaire
      was used that ranked their attitudes according to the 5-grade Likert scale. The
      study included 250 women who gave birth to their first child. Of these
      pregnancies, 125 had been obtained by means of ART; the remaining 125 were
      naturally conceived. RESULTS: Difficulties in adaptation to pregnancy were
      significantly more frequent in women whose pregnancies resulted from the use of
      ARTs than in those who had conceived naturally (p = 0.000005). The subjects in
      the first group were significantly older (p = 0.04), more affluent (p = 0.000005)
      and had more frequently interrupted their professional work than women in the
      latter group. The two groups did not differ with regard to frequency of
      hospitalisations. CONCLUSIONS: ART significantly increases difficulties in
      adaptation to resulting pregnancies. The main factors responsible for these
      difficulties are age, socio-economic conditions and interruption of professional
      activity.

PMID- 17455046
TI  - Health literacy and contraception: a readability evaluation of contraceptive
      instructions for condoms, spermicides and emergency contraception in the USA.
AB  - OBJECTIVE: To assess readability of over-the-counter (OTC) contraceptive product
      instructions currently available, compare the results with previous studies from
      a decade ago, and review the implications for health care providers, in
      particular pharmacists counseling on OTC contraceptives. METHODS: A sample of
      contraceptive instructions was submitted to a readability analysis using four
      standard readability formulas. Products included condoms, spermicides, and
      emergency contraception instruction pamphlets. RESULTS: Reading grade levels for
      condoms ranged from 6th to 12th grade. The average reading levels for the
      spermicides were 9th-10th grade and for the emergency contraceptives 10th-12th
      grade. These results were consistent with those of similar studies performed a
      decade ago. CONCLUSIONS: Consumers need to have at least a high school reading
      level in order to comprehend current product instructions. Very little has
      changed in the past decade regarding readability of OTC contraceptive patient
      instructions, despite calls to simplify written instructions. Healthcare
      providers, in particular pharmacists, must be aware of these disparities to
      enhance patient education and advocate for simpler reading materials.

PMID- 17455047
TI  - Emergency contraception: knowledge and attitudes of Turkish nursing and midwifery
      students.
AB  - OBJECTIVES: To assess the knowledge and attitudes of emergency contraception (EC)
      among nursing and midwifery students of a university in the Eastern-Mediterranean
      region of Turkey. METHODS: The survey was conducted among 210 nursing and
      midwifery students. RESULTS: One hundred and twenty-five participants (59.5%)
      knew at least one method of EC. One hundred and fourteen participants (54.3%) had
      heard about emergency contraceptive pills (ECPs), but only 17 (8.1%) knew what
      they contained. Rates of hearing about ECPs were statistically higher in third
      and fourth classes than first and second classes, and in midwifery students than
      in nursing students (P < 0.001). In spite of their very unsatisfactory level of
      knowledge, 166 students (79.0%) thought that ECPs should be sold in pharmacies.
      CONCLUSION: The nursing and midwifery students we assessed have a very
      insufficient knowledge of EC. Probably therefore, many are prejudiced against it.
      They should be much better acquainted with this modality of contraception since,
      after graduation, they will play an important role in the dissemination of
      information about EC in the population.

PMID- 17455048
TI  - The role of men in family planning decision-making in rural and urban Nigeria.
AB  - OBJECTIVES: To determine the role of men in family planning decision-making in
      both rural and urban areas of Nigeria. METHODS: A total number of 370 married men
      (244 rural and 126 urban) were interviewed using a pre-tested, semi-structured
      interviewer based questionnaire. The study was conducted in the Iwaro community
      in Atakumosa West Local Government area (rural men) and the Oranfe Community in
      Ife East Local government area (urban men), both in Osun State, South West
      Nigeria. RESULTS: The results showed a high level of awareness of family planning
      among both study groups (98.3% rural and 98.4% urban). Most men in both groups
      believe that a decision about family planning should be made jointly by the
      spouses instead of being the prerogative of either. This contrasts with the
      generally held belief that men are opposed to family planning and a take
      predominant role in contraceptive decision-making. The condom was the most
      commonly known and used method with a preponderance among urban (81.1%) over
      rural men (69.4%). Many men would use family planning if their wives demanded it.
      However, most respondents in both study groups believed that men should not
      accompany their wives to the family planning centre to obtain contraceptive
      supplies and advice. CONCLUSION: Deciding about contraception should be done
      jointly by men and women in South West Nigeria.

PMID- 17455049
TI  - Correlates of physicians' attitudes toward communication with HIV/AIDS patients
      in Ile-Ife, Nigeria.
AB  - OBJECTIVES: The study assessed physicians' perceptions of HIV/AIDS patients and
      identified the determinants of physicians' attitudes toward communication with
      HIV/AIDS patients in Ile-Ife, Nigeria. METHODS: A semi-structured questionnaire
      was used to elicit information from 110 physicians in a cross-sectional survey,
      while in-depth interviews were conducted with 10 people living with HIV/AIDS
      (PLWHA) who had been previously admitted under the care of the physicians.
      Univariate, bivariate and multivariate analyzes were conducted. RESULTS: Although
      most physicians perceived PLWHA positively and 58% of them displayed a positive
      attitude toward communication with PLWHA under their care, the expectations of
      the patients concerning HIV/AIDS communication were not being met. Only 43% of
      physicians expressed any degree of comfort engaging PLWHA in lengthy discussions
      or communicating the diagnosis of HIV to patients. The strongest correlates of
      physicians' positive attitude were previous exposure to HIV/AIDS counseling, the
      number of HIV/AIDS patients treated per month, the number of years spent in the
      care of PLWHA, and the gender of the physicians (p < 0.05). CONCLUSIONS:
      Physicians in Ile-Ife, Nigeria are not adequately equipped by way of training to
      effectively meet the expectations of their patients concerning HIV/AIDS
      communication. The large number of PLWHA in the country calls for urgent
      attention to address this important aspect of care.

PMID- 17455051
TI  - Word chunk frequencies affect the processing of pronominal object-relative
      clauses.
AB  - We present experimental support for the view that fine-grained statistical
      information may play a crucial role in the processing of centre-embedded
      linguistic structure. Using both offline and online methods, we show that the
      processing of pronominal object-relative clauses is influenced by the frequency
      of co-occurrence of the word combinations (chunks) forming the clause. We use
      materials that are controlled for capacity-based factors that have been
      previously shown to influence comprehension of relative clauses. The results
      suggest that, other factors being equal, the frequency of the word chunk forming
      the clause affects processing difficulty. Analyses of the data indicate that the
      results cannot be explained by differential access to individual lexical items.
      Following recent constructivist approaches, we argue that frequency of co
      occurrence influences the chunking mechanism by which multiword sequences may
      become fused into processing units that are easier to access.

PMID- 17455050
TI  - Fertility preferences, contraceptive behaviors and unmet needs: a gap between
      urban and suburban parts of a city.
AB  - OBJECTIVES: To explore the differences in unwanted fertility in different parts
      of a city. METHODS: Data were obtained from the 1999 Manisa Demographic and
      Health Survey (MDHS) in Turkey. We collected information from a representative
      sample of 1728 ever-married women aged 15-49 years on fertility, fertility
      preferences, unmet need for family planning, contraceptive discontinuation, and
      abortion. Data were analyzed using SPSS 10.0 for Windows. RESULTS: Of the persons
      studied, 1238 (71.6%) were living in urban settlements and 490 (28.4%) in
      suburban (gecekondu) settlements. The total fertility rate is higher among
      gecekondu women (2.42) than among urban women (2.14) although gecekondu women
      have a lower wanted fertility rate (1.54) than urban women (1.77). Married women
      in the urban area were currently using a contraceptive method more frequently
      (75.6%) than those living in the gecekondu area (61.7%) (OR 2.5; 95% CI 1.9-3.2;
      p < 0.001). The unmet need percentage in gecekondu women (17.7%) is higher than
      in urban women (8.3%; p < 0.001). The induced abortion rate is higher in urban
      women (14.8 per 1000 pregnancies) than in gecekondu women (7.1 per 1000
      pregnancies; OR 2.1; 95% CI 1.4-3.1; p < 0.001). CONCLUSIONS: There are
      inequalities in the achievement of fertility preferences and in accessibility to
      family planning services between urban and suburban parts of the city.

PMID- 17455052
TI  - "They" as a gender-unspecified singular pronoun: eye tracking reveals a
      processing cost.
AB  - The plural pronouns they and them are used to refer to individuals with unknown
      gender and when a random allocation of gender is undesirable. Despite this
      apparently felicitous usage, "singular they/them" should raise processing
      problems under the theory that pronouns seek gender- and number-matched
      antecedents. Using eye-tracking, we investigated whether there was any processing
      cost associated with using singular they/them. There was a clear cost of number
      incompatibility for they/them. Thus, although singular they/them is in current
      usage, it does not appear that they/them is immediately tolerant of a plural
      antecedent, though such may be rapidly accommodated. The data are consistent with
      the search account of pronoun resolution and preserve the semantics of they/them
      as denoting plurality.

PMID- 17455053
TI  - The cause of the within-language Stroop superiority effect and its implications.
AB  - This study examines the causes for the within-language Stroop superiority effect
      (WLSSE; larger Stroop effect for words appearing in the response language than in
      another language). Participants named in their first language (L1) or second
      language (L2) the colour of colour-words or colour-associated words appearing in
      L1 or in L2. The WLSSE was limited for colour-words. It was concluded that for
      colour-words, the cause for the WLSSE is that words appearing in the within
      language condition belong to the response set, whereas words in the between
      language condition do not. This finding challenges previous suggestions that a
      nonrelevant stimulus language can be suppressed.

PMID- 17455054
TI  - A conjunctive feature similarity effect for visual search.
AB  - Traditional models of visual search assume interitem similarity effects arise
      from within each feature dimension independently of other dimensions. In the
      present study, we examine whether distractor-distractor effects also depend on
      feature conjunctions (i.e., whether feature conjunctions form a separate
      "feature" dimension that influences interitem similarity). Spatial frequency and
      orientation feature dimensions were used to generate distractors. In the bound
      condition, the number of distractors sharing the same conjunction of features was
      higher than that in the unbound condition, but the sharing of features within
      frequency and orientation dimensions was the same across conditions. The results
      showed that the target was found more efficiently in the bound than in the
      unbound condition, indicating that distractor-distractor similarity is also
      influenced by conjunctive representations.

PMID- 17455055
TI  - Effort during visual search and counting: insights from pupillometry.
AB  - We investigated the processing effort during visual search and counting tasks
      using a pupil dilation measure. Search difficulty was manipulated by varying the
      number of distractors as well as the heterogeneity of the distractors. More
      difficult visual search resulted in more pupil dilation than did less difficult
      search. These results confirm a link between effort and increased pupil dilation.
      The pupil dilated more during the counting task than during target-absent search,
      even though the displays were identical, and the two tasks were matched for
      reaction time. The moment-to-moment dilation pattern during search suggests
      little effort in the early stages, but increasingly more effort towards response,
      whereas the counting task involved an increased initial effort, which was
      sustained throughout the trial. These patterns can be interpreted in terms of the
      differential memory load for item locations in each task. In an additional
      experiment, increasing the spatial memory requirements of the search evoked a
      corresponding increase in pupil dilation. These results support the view that
      search tasks involve some, but limited, memory for item locations, and the effort
      associated with this memory load increases during the trials. In contrast,
      counting involves a heavy locational memory component from the start.

PMID- 17455056
TI  - The role of prior task experience in temporal misestimation.
AB  - The effect of experience with a preceding task on the accuracy of predictions of
      duration was examined in three experiments, where two tasks comprising similar or
      different mental operators were performed consecutively. Results supported an
      anchoring account of misestimation, which states that misestimation occurs
      because predictions are anchored to the duration of the preceding task. Preceding
      performance of a longer task led to overestimation on a shorter task with similar
      mental operators (Experiment 1), whereas preceding performance of a shorter task
      comprising similar or different mental operators led to underestimation on a
      longer task (Experiments 1 to 3). Contrary to the planning fallacy account
      (Kahneman & Tversky, 1979), these findings indicate that preceding task
      performance is considered when predicting duration, but that using such
      information does not necessarily improve accuracy.

PMID- 17455057
TI  - The role of visual attention in action priming.
AB  - It has been demonstrated that the task-irrelevant left-right orientation of an
      object is capable of facilitating left-right-hand responses when the object is
      orientated towards the responding hand. We investigated the role of attention in
      this orientation effect. Experiment 1 showed that object orientation facilitates
      responses of the hand that is compatible with the object's orientation, despite
      the entire object being irrelevant. However, when a task-relevant fixation point
      was displayed over the prime object in Experiment 2, the effect was not observed.
      Together Experiments 1 and 2 suggest that the orientation information of viewed
      objects primes the action selection processes even when the object is irrelevant,
      but only when attention is not allocated to a competing stimulus during the prime
      presentation. Experiment 3 suggested that the elimination of the effect in
      Experiment 2 could not be attributed to the elimination of an attentional shift
      to the graspable part of the prime. Finally, Experiment 4 showed that object
      orientation can evoke an abstract response code, influencing the selection of
      finger responses.

PMID- 17455058
TI  - The role of goal representations in moving to temporal and spatial targets.
AB  - Traditionally, movement kinematics are thought to reflect physical properties
      (e.g., position and time) of movement targets. However, targets may also evoke
      intentional goals like "to be in a certain position at a given time". Therefore,
      kinematics may be viewed not as a reaction to stimuli, but rather as the means to
      attain intended goals. In the present study participants performed continuous
      reversal movements. It was first shown that kinematics towards temporal and
      spatial targets differ from kinematics away from those targets. Further,
      kinematics are different for movements to temporal (relatively short movement
      times, high and late peak velocity) and spatial (relatively long movement times,
      early peak velocity) targets (Experiments 1 and 2). In order to obtain evidence
      for the influence of goal representations on kinematics, combinations of temporal
      and spatial targets were investigated in Experiments 3 and 4. Specifically, the
      conditions were: spatial targets always present with varying temporal targets,
      temporal targets always present with varying spatial targets, and combined and
      separate spatial and temporal targets. Not only the physical features, but also
      how the targets were represented as movement goals, were important. Thus,
      movement kinematics do not simply reflect stimulus properties, but rather the
      representation of the intended goal.

PMID- 17455059
TI  - The phonological loop unmasked? A comment on the evidence for a "perceptual
      gestural" alternative.
AB  - Jones et al. (Jones, Hughes, & Macken, 2006; Jones, Macken, & Nicholls, 2004)
      identify the interaction between phonological similarity, articulatory
      suppression, and stimulus presentation mode in verbal short-term memory as
      potentially providing important support for the phonological loop hypothesis.
      They find such an interaction but attribute it to "perceptual organization
      masquerading as phonological storage". We present data using shorter letter
      sequences and find clear evidence of the interaction predicted by the
      phonological loop hypothesis, which, unlike the evidence of Jones et al., is not
      limited to recency, and which provides continued support for the phonological
      loop hypothesis.

PMID- 17455060
TI  - Commentary on Baddeley and Larsen (2007). The phonological store abandoned.
AB  - Baddeley and Larsen (2007) argue that a number of key findings reported by Jones,
      Macken, and Nicholls (2004) and Jones, Hughes, and Macken (2006) pointing to
      shortcomings of the phonological store construct arise from the store being
      abandoned with long lists. In our rejoinder we point out that Baddeley and Larsen
      use a procedure in which retrieval from the supposed phonological storage would
      not--according to their own theory--have been possible, and we present
      theoretical, empirical, and logical problems with their "store abandonment"
      argument and highlight a number of difficulties associated with the
      interpretation of suffix and prefix effects. We conclude that our data are still
      problematic for the phonological store construct and suggest that a reformulation
      of short-term memory theory needs to embody (or indeed focus exclusively upon)
      perceptual and effector systems rather than bespoke storage modules.

PMID- 17455062
TI  - Exploring the role of characteristic motion when learning new faces.
AB  - Previous research has shown that it is easier to recognize familiar faces when
      shown moving, rather than static, especially when viewing conditions are
      difficult (Knight & Johnston, 1997; Lander, Christie, & Bruce, 1999). One
      possible theoretical reason for the moving-face advantage is that we learn
      "characteristic motion signatures" for familiar faces, associated with the face
      representation in memory. To examine this idea we investigated the role of motion
      at test when learning faces from either static images or moving sequences
      (Experiment 1). Results suggest that there is only an advantage for motion at
      test when the face is learned moving. In Experiment 2 we map the importance of
      facial motion as a face becomes increasingly familiar, on a television drama. We
      demonstrate that the beneficial effect of motion is not dependent on the amount
      of time the face is viewed. Results from both experiments support the idea of
      rapidly learned characteristic motion patterns.

PMID- 17455063
TI  - Instrument specificity in experienced musicians.
AB  - Previous studies have shown that experienced pianists have acquired integrated
      action-effect (A-E) associations. In the present study, we were interested in how
      specific these associations are for the own instrument by investigating pianists
      and guitarists. A-E associations were examined by testing whether the perception
      of a "potential" action-effect has an influence on actions. Participants played
      chords on their instrument in response to visual stimuli, while they were
      presented task-irrelevant auditory distractors (congruent or incongruent) in
      varying instrument timbre. In Experiment 1, pianists exhibited an interference
      effect with timbres of their own instrument category (keyboard instruments: piano
      and organ). In Experiment 2 guitarists showed an interference effect only with
      guitar timbre. Thus, integrated A-E associations primarily seem to consist of a
      specific component on a sensory-motor level involving the own instrument.
      Additionally, categorical knowledge about how an instrument is played seems to be
      involved.

PMID- 17455064
TI  - Optional-shift behaviour in rats: a novel procedure for assessing attentional
      processes in discrimination learning.
AB  - A novel, optional-shift procedure was used to assess changes in the attention
      paid to stimuli that occur over the course of discrimination learning. In Phase
      1, rats were trained on a conditional instrumental discrimination using
      audiovisual stimulus compounds; one stimulus dimension (auditory or visual) was
      relevant to the solution of the discrimination, the other was irrelevant. In
      Phase 2, all animals received three sessions of training with novel audiovisual
      compounds where both dimensions were equally diagnostic. Results from probe test
      trials indicated that, during Phase 2, animals learnt most about cues belonging
      to the stimulus dimension that was relevant during Phase 1. These results suggest
      that over the course of discrimination learning there was an increase in the
      amount of attention paid to relevant stimuli and/or a decrease in the attention
      paid to irrelevant stimuli.

PMID- 17455065
TI  - Reinstating effortful encoding operations at test enhances episodic remembering.
AB  - Two experiments investigated the effects of reinstating encoding operations on
      remember and know responses in recognition memory. Experiment 1 showed that
      reinstating an effortful encoding task (generating words from fragments)
      increased remember responses at test but reinstating an automatic encoding task
      (reading intact words) did not. This pattern was confirmed in Experiment 2 in
      which words were either read intact or generated from anagrams. These findings
      show that repeating effortful (but not automatic) encoding operations at test
      cues not only the recognition of the information that was acquired via those
      operations but also the conscious recollection of the encoding episode.

PMID- 17455066
TI  - Reality monitoring and resistance to forgetting under short delay intervals.
AB  - In three experiments, participants were asked to perform simple action statements
      or to imagine performing the actions in a single study session. In a test session
      that occurred 1 hr, 24 hr, 48 hr (Experiments 1a and 1b), or 1 week later
      (Experiments 2 and 3), participants were instructed to tell whether the action
      statement had been carried out or imagined. The primary finding was that,
      overall, recognition and reality monitoring showed a comparable rate of
      forgetting. The results add evidence to the hypothesis that, also after long
      retention delays, discrimination between an internal and an external source may
      not be inferior to item recognition. A new theoretical proposal to account for
      these findings is outlined.

PMID- 17455067
TI  - Enhancing challenged students' recognition of mathematical relations through
      differential outcomes training.
AB  - Previous studies have reported that the differential outcomes procedure enhances
      learning and memory in special populations with cognitive deficits (see Goeters,
      Blakely, & Poling, 1992, for a review). In the present study we extend these
      findings to healthy adults who were asked to discriminate between the symbols " >
      " and " < " in mathematical statements. In Experiment 1, the performance of
      participants who showed difficulties in discriminating between these symbols was
      better (shorter response times) for the differential outcomes condition than for
      the nondifferential outcomes condition. In Experiment 2, the difficulty of the
      task was increased by using signed decimal numbers. Similar to Experiment 1,
      participants who initially had difficulties in discriminating between the symbols
      showed better performance (higher accuracy) for the differential outcomes
      condition than for the nondifferential outcomes condition, but only when both
      numbers were negative. These findings suggest that the differential outcomes
      procedure can be used to improve performance of challenged healthy adults on
      discrimination tasks with mathematical symbols and relations.

PMID- 17455068
TI  - The homophone effect in semantic access tasks using kanji words: its relation to
      the articulatory suppression effect.
AB  - The present study examined whether articulatory suppression influences homophone
      effects in semantic access tasks using Japanese kanji words. In Experiment 1,
      participants were required to decide whether visually presented word pairs were
      synonyms. This experiment replicated the homophone effect observed in previous
      research that showed more false positive errors in response to nonsynonym
      homophone pairs than to controls. The present study found that this homophone
      effect was also obtained under an articulatory suppression condition. In
      Experiment 2, participants performed a semantic decision task, in which they had
      to judge whether a visually presented target word was an exemplar of a definition
      that was shown immediately before presentation of the target word. The homophone
      effect observed in previous studies was replicated--that is, longer response
      times and more false positive errors were associated with homophones of correct
      exemplars than with nonhomophone control words. This homophone effect was also
      obtained under an articulatory suppression conditions. These results suggest that
      the phonological processing that produces the homophone effects in semantic
      access tasks using Japanese kanji words does not include articulatory mechanisms.

PMID- 17455069
TI  - Dissociative effects of viewpoint and semantic priming on action and semantic
      decisions: evidence for dual routes to action from vision.
AB  - This article reports evidence that two variables--object viewpoint and semantic
      priming--differentially affect action and semantic decisions to objects. Changing
      the viewing angle of an object, so that its graspable parts are oriented away
      from observers, disrupted action decisions but had little effect on semantic
      categorization. In contrast, semantic priming influenced semantic categorization
      and object naming, but not action decisions. Action priming, however, did not
      affect performance. These selective effects are consistent with the existence of
      separate semantic and direct (nonsemantic) routes to action from vision.

PMID- 17455070
TI  - Revisiting places passed: sensitization of exploratory activity in rats with
      hippocampal lesions.
AB  - We examined the involvement of the hippocampus in short-term changes in
      exploratory behaviour in an open field (Experiment 1) and experimental contexts
      (Experiment 2). In Experiment 1, rats with excitotoxic lesions of the hippocampus
      were more likely to revisit recently visited zones within the open field than
      were control rats. Similarly, in Experiment 2 rats with hippocampal lesions
      showed greater exploration of a context that they had recently explored than a
      context that they had less recently explored. This short-term sensitization
      effect was not evident in control rats. These findings are consistent with the
      suggestion that the recent presentation of a stimulus has two opposing effects on
      behaviour, sensitization, and habituation, and that hippocampal lesions disrupt
      the short-term process responsible for habituation, but not that responsible for
      sensitization.

PMID- 17455071
TI  - On the basis of belief in causal and diagnostic conditionals.
AB  - According to the suppositional theory of conditionals, people assess their belief
      in a conditional statement of the form "if p then q" by conducting a mental
      simulation on the supposition of p in which they assess their degree of belief in
      q. This leads to them to the judge the probability of a conditional statement to
      be equal to the conditional probability, P(q|p). Evidence for this conditional
      probability hypothesis has been adduced in earlier studies for abstract, causal,
      and counterfactual conditionals. For the realistic conditionals, it is natural to
      assume that people perform such mental simulations by building causal mental
      models from prior causes to later effects. However, in the present study we show
      that the conditional probability hypothesis extends to diagnostic conditionals,
      which relate effects to causes. This new finding presents a major challenge for
      theoretical accounts of the mental processing of conditional statements.

PMID- 17455073
TI  - What causes the effect of age of acquisition in lexical processing?
AB  - Three hypotheses for effects of age of acquisition (AoA) in lexical processing
      are compared: the cumulative frequency hypothesis (frequency and AoA both
      influence the number of encounters with a word, which influences processing
      speed), the semantic hypothesis (early-acquired words are processed faster
      because they are more central in the semantic network), and the neural network
      model (early-acquired words are faster because they are acquired when a network
      has maximum plasticity). In a regression study of lexical decision (LD) and
      semantic categorization (SC) in Italian and Dutch, contrary to the cumulative
      frequency hypothesis, AoA coefficients were larger than frequency coefficients,
      and, contrary to the semantic hypothesis, the effect of AoA was not larger in SC
      than in LD. The neural network model was supported.

PMID- 17455072
TI  - Age-related increase in top-down activation of visual features.
AB  - Previous research suggests that, during visual search and discrimination tasks,
      older adults place greater emphasis than younger adults on top-down attention.
      This experiment investigated the relative contribution of target activation and
      distractor inhibition to this age difference. Younger and older adults performed
      a singleton discrimination task in which either an E or an R target (colour
      singleton) was present among distractor letters. Relative to a baseline condition
      in which the colours of the targets and distractors remained constant, an age
      related slowing of performance was evident when either the colour of the target
      or that of the distractors varied across trials. The age-related slowing was more
      pronounced in response to target colour variation, suggesting that older adults
      place relatively greater emphasis on the top-down activation of target features.

PMID- 17455074
TI  - Tracking recognition of spoken words by tracking looks to printed words.
AB  - Eye movements of Dutch participants were tracked as they looked at arrays of four
      words on a computer screen and followed spoken instructions (e.g., "Klik op het
      woord buffel": Click on the word buffalo). The arrays included the target (e.g.,
      buffel), a phonological competitor (e.g., buffer, buffer), and two unrelated
      distractors. Targets were monosyllabic or bisyllabic, and competitors mismatched
      targets only on either their onset or offset phoneme and only by one distinctive
      feature. Participants looked at competitors more than at distractors, but this
      effect was much stronger for offset-mismatch than onset-mismatch competitors.
      Fixations to competitors started to decrease as soon as phonetic evidence
      disfavouring those competitors could influence behaviour. These results confirm
      that listeners continuously update their interpretation of words as the evidence
      in the speech signal unfolds and hence establish the viability of the methodology
      of using eye movements to arrays of printed words to track spoken-word
      recognition.

PMID- 17455075
TI  - Two dissociable aspects of feeling-of-knowing: knowing that you know and knowing
      that you do not know.
AB  - Feeling-of-knowing judgement is traditionally regarded as a unitary cognitive
      process. However, recent research suggests that knowing that you know (positive
      feeling-of-knowing) and knowing that you do not know (negative feeling-of
      knowing) have different neural substrates (Luo, Niki, Ying, & Luo, 2004). In the
      present study, we used a paradigm adapted from Koriat and Levy-Sadot (2001) to
      examine whether positive feeling-of-knowing and negative feeling-of-knowing were
      mediated by distinct cognitive processes. We found that positive and negative
      feeling-of-knowing were dissociated during immediate feeling-of-knowing
      judgements (i.e., preliminary feeling-of-knowing) and delayed feeling-of-knowing
      judgements (i.e., postretrieval feeling-of-knowing). At the judgement intervals,
      positive feeling-of-knowing was based on partial recovery of the nonrecalled
      targets, whereas negative feeling-of-knowing was determined by familiarity with
      the retrieval cues. Our results suggest that feeling-of-knowing is a
      heterogeneous process.

PMID- 17455076
TI  - Searching for Shereshevskii: what is superior about the memory of synaesthetes?
AB  - Some individuals with superior memory, such as the mnemonist Shereshevskii
      (Luria, 1968), are known to have synaesthesia. However, the extent to which
      superior memory is a general characteristic of synaesthesia is unknown, as is the
      precise cognitive mechanism by which synaesthesia affects memory. This study
      demonstrates that synaesthetes tend to report subjectively better than average
      memory and that these reports are borne out with objective testing. Synaesthetes
      experiencing colours for words show better memory than matched controls for
      stimuli that induce synaesthesia (word lists) relative to stimuli that do not (an
      abstract figure). However, memory advantages are not limited to material that
      elicits synaesthesia because synaesthetes demonstrate enhanced memory for colour
      per se (which does not induce a synaesthetic response). Our results suggest that
      the memory enhancement found in synaesthetes is related to an enhanced retention
      of colour in both synaesthetic and nonsynaesthetic situations. Furthermore, this
      may account for the fact that synaesthetic associations, once formed, remain
      highly consistent.

PMID- 17455077
TI  - Inhibition of return impairs episodic memory access.
AB  - The term inhibition of return (IOR) refers to a bias against returning attention
      to a location or object that has recently been attended. The effect has been
      shown to occur in various perceptual tasks including stimulus detection,
      localization, and discrimination, but also to affect higher cognitive processes
      like lexical access. The present experiments examined whether inhibition of
      return would impair the high-level processing that is required in accessing item
      representations in episodic memory. The results show that reaction times for
      recognition memory decisions are increased under IOR. Furthermore, IOR affects
      the accuracy of recognition memory, and this effect interacts with the ease of
      memory access, manipulated, for example, by encoding depth in the learning phase.
      These results suggest that IOR impairs attentional processing up to the highest
      cognitive levels, including the access of prior item encounters in episodic
      memory.

PMID- 17455078
TI  - The role of working memory in the carry operation of mental arithmetic: number
      and value of the carry.
AB  - Two experiments were conducted to investigate the role of phonological and
      executive working-memory components in the carry operation in mental arithmetic.
      We manipulated the number of carry operations, as previous research had done, but
      also the value that had to be carried. Results of these experiments show that in
      addition to the number of carry operations, the value of the carry is also an
      important variable determining the difficulty of arithmetical sums. Furthermore,
      both variables (number and value) interacted with each other in such a way that
      the combination of multiple carries and values of carries larger than one
      resulted in more difficult problems irrespective of the presence of a working
      memory load. The findings with respect to working-memory load suggest that mainly
      the central executive is important in handling the number of carry operations as
      well as the value that has to be carried. The implications of the present
      findings for our views on mental arithmetic and its reliance on working memory
      are discussed.

PMID- 17455079
TI  - Order information and free recall: evaluating the item-order hypothesis.
AB  - The item-order hypothesis proposes that order information plays an important role
      in recall from long-term memory, and it is commonly used to account for the
      moderating effects of experimental design in memory research. Recent research
      (Engelkamp, Jahn, & Seiler, 2003; McDaniel, DeLosh, & Merritt, 2000) raises
      questions about the assumptions underlying the item-order hypothesis. Four
      experiments tested these assumptions by examining the relationship between free
      recall and order memory for lists of varying length (8, 16, or 24 unrelated words
      or pictures). Some groups were given standard free-recall instructions, other
      groups were explicitly instructed to use order information in free recall, and
      other groups were given free-recall tests intermixed with tests of order memory
      (order reconstruction). The results for short lists were consistent with the
      assumptions of the item-order account. For intermediate-length lists, explicit
      order instructions and intermixed order tests made recall more reliant on order
      information, but under standard conditions, order information played little role
      in recall. For long lists, there was little evidence that order information
      contributed to recall. In sum, the assumptions of the item-order account held for
      short lists, received mixed support with intermediate lists, and received no
      support for longer lists.

PMID- 17455080
TI  - Review of the application of RNA interference technology in the pharmaceutical
      industry.
AB  - Ribonucleic acid (RNA) interference (RNAi) is a recently discovered phenomenon
      whereby the introduction of double stranded (ds) RNA into the cytoplasm of the
      cell results in the specific and efficient degradation of complementary messenger
      (m) RNA and, therefore, reduced protein production. It was discovered by chance
      during attempts to develop flowers with increased colour intensity. The specific
      nature of the inhibition of protein production of cells has resulted in an
      explosion of research to understand and exploit RNAi. The technique is now
      established in in vitro systems, and much work is focussed in adapting RNAi for
      in vivo application. The potential of the technology in understanding
      physiological and pathological processes is significant, while its development as
      a therapeutic agent holds much promise as targeted agents. This review will
      describe the basic biological processes that drive RNAi, indicate current areas
      of areas research, and forecast future areas of development.

PMID- 17455081
TI  - Investigations of rodent urinary bladder carcinogens: collection, processing, and
      evaluation of urine and bladders.
AB  - Examination of the urine and the bladder epithelium are essential to the
      investigation of mechanisms of urinary bladder carcinogens in rodents. However,
      urine and bladder tissue specimens must be collected and processed properly if
      accurate data are to be derived. The optimum specimen for analysis of urinary
      constituents is fresh void urine collected from nonfasting animals. Fasting the
      animal prior to urine collection changes the normal composition, including pH.
      Many of the normal urinary constituents can influence the mode of action of
      bladder carcinogens, especially for non-genotoxic agents. Light microscopy is
      routinely used to examine the bladder epithelium. However, it is often necessary
      to use more sensitive techniques, such as scanning electron microscopy (SEM) to
      detect subtle cytotoxic changes in the superficial cell layer of the urothelium,
      and bromodeoxyuridine (BrdU) incorporation, PCNA, or Ki-67 immunohistochemistry
      to determine the labeling index for cell proliferation. The urinary bladder must
      be handled gently and inflated with fixative in situ before the animal dies to
      avoid artifactual autolytic damage to the bladder epithelium that is visible by
      SEM and may be mistaken for treatment-related changes. The purpose of this paper
      is to provide information for the proper collection and examination of urine and
      the urinary bladder.

PMID- 17455082
TI  - Expression of thyroglobulin and calcitonin in spontaneous thyroid gland tumors in
      the Han Wistar rat.
AB  - Spontaneous follicular and C-cell tumors of the thyroid gland in the Han Wistar
      rat were examined using two morphologic procedures. Firstly, in situ
      hybridization (ISH) was used to localize thyroglobulin (TG) and calcitonin (CT)
      mRNAs. Secondly, the proteins for these markers were detected using
      immunohistochemistry (IHC). The aim was to study the morphology of the tumors and
      to examine the usefulness of TG and CT markers in the differential diagnosis of
      these lesions. Follicular tumors with cystic, papillary and follicular patterns
      showed relatively consistent expression of TG mRNA by ISH, thereby confirming the
      diagnostic value of this technique. However, no staining for TG markers was
      observed in solid lesions. In general, C-cell tumors comprised well
      differentiated cells that continued to express CT mRNA and peptides even after
      embolic spread and metastasis. Therefore, the performance of either ISH or IHC
      for CT markers can be used for diagnostic confirmation. Additional features noted
      in C-cell tumors included the appearance of tumor emboli or metastases in
      association with small primary lesions (less than 5 average follicular diameters
      in size) and the presence of eosinophilic (amyloid-like) material showing
      immunopositivity for CT peptides. Finally, evidence is provided for the
      sequestration of TG protein by proliferating C-cells.

PMID- 17455083
TI  - Polychlorinated biphenyl exposure causes gonadal atrophy and oxidative stress in
      Corbicula fluminea clams.
AB  - Polychlorinated biphenyls (PCBs) are widespread environmental contaminants that
      have been linked to oxidative and other toxic effects in both humans and
      wildlife. Due to recent environmental health concerns at a PCB contaminated
      Superfund site near Raleigh, NC, we used a common clam species (Corbicula
      fluminea) as surrogates to isolate the effects of PCBs on threatened bivalves
      native to the region. Under controlled laboratory conditions, clams were exposed
      to 0, 1, 10, or 100 ppb Aroclor 1260 in the ambient water for 21 days. Measured
      biomarkers spanned a range of effective levels of biological organization
      including low molecular weight antioxidants, lipid-soluble antioxidants, and
      whole tissue radical absorption capacity. These data were augmented by use of
      histological evaluation of whole samples. Aroclor 1260 significantly increased
      reduced glutathione (GSH) and total protein concentrations at all treatments
      levels. Significant decreases were measured in all treatments in gamma 
      tocopherol and total oxidant scavenging capacity (TOSC) and alpha -tocopherol
      values in the 100 ppb exposure. Histologically, Aroclor 1260 caused significant
      gonadal atrophy, effacement of gonad architecture with accumulations of Brown
      cells, and inflammation and necrosis in digestive glands and foot processes. Our
      results indicate that oxidative mechanisms play a significant role in the
      decreased health of these clams due to exposure to Aroclor 1260. The changes in
      the gonads of exposed clams suggest that a serious threat to bivalve reproduction
      exists due to PCB exposure.

PMID- 17455084
TI  - A comprehensive antibody panel for immunohistochemical analysis of formalin
      fixed, paraffin-embedded hematopoietic neoplasms of mice: analysis of mouse
      specific and human antibodies cross-reactive with murine tissue.
AB  - Immunohistochemistry is an indispensable tool in human pathology enabling
      immunophenotypic characterization of tumor cells. Immunohistochemical analyses of
      mouse models of human hematopoietic neoplasias have become an important aspect
      for comparison of murine entities with their human counterparts. The aim of this
      study was to establish a diagnostic antibody panel for analysis of murine
      lymphomas/leukemias, useful in formalin-fixed/paraffin-embedded tissue. Overall,
      48 antibodies (4 rabbit monoclonal, 12 rabbit polyclonal, 2 goat polyclonal, 11
      rat, and 19 mouse monoclonal), which were either mouse-specific (14) or cross
      reactive with murine tissue (34) were tested for staining quality and diagnostic
      value in 468 murine hematopoietic neoplasms. Specific staining was achieved with
      29 antibodies, of which 18 were human antibodies cross-reactive with murine
      tissue. Only 23 (B220, BCL-2, BCL-6, CD117, CD138 (2x), CD3 (2x), CD43, CD45,
      CD5, CD79 alpha cy, cyclin D1, Ki-67 (2x), Mac-3, Mac-2, lysozyme, mast cell
      tryptase, MPO, Pax-5, TdT, and TER-119) were regarded as valuable for diagnostic
      evaluation. Immunohistochemistry was also established in an automated
      immunostainer for high throughput analysis. The antibody panel developed is
      useful for the classification of murine lymphomas and leukemias analyzed, and a
      valuable tool for human and veterinary pathologists involved in the diagnostic
      interpretation of murine models of hematopoietic neoplasias.

PMID- 17455085
TI  - Molecular pathological evaluation of clusterin in a rat model of unilateral
      ureteral obstruction as a possible biomarker of nephrotoxicity.
AB  - In the present study, to determine the validity of considering clusterin as a
      possible biomarker of nephrotoxicity, the expression and distribution of
      clusterin in the rat UUO kidney were investigated. Real-time RT-PCR revealed an
      immediate increase in the clusterin mRNA level in the kidney, within 6 hours
      after UUO, and also maintenance of the mRNA expression level from day-1 to day-3
      was 60-fold higher in the UUO kidney than in the sham kidney. ISH analysis
      revealed clusterin mRNA signals in the UUO renal tubular epithelium, whereas no
      signal was observed in the sham kidney. Detection of clusterin-alpha and -beta
      was conducted using the subtype-specific antibodies, by both of western blotting
      and immunohistochemistry. Although clusterin-alpha was predominant in the UUO
      urine, only faint signals were noted at the brush border of the tubular
      epithelium or intraductal. On the other hand, strong signals of clusterin-beta
      were detected in the UUO kidney homogenate, and the molecule was localized in the
      renal tubular epithelium. These results suggest that clusterin was translated in
      the renal tubular epithelium after de novo expression induced by renal injury.
      Thus, detection of clusterin mRNA and clusterin-beta in the kidney or clusterin
      alpha in the urine may be useful for predicting nephrotoxicity.

PMID- 17455086
TI  - Occult cardiotoxicity: subtoxic dosage of Bis(2-chloroethoxy)methane impairs
      cardiac response to simulated ischemic injury.
AB  - The effect of Bis(2-chloroethoxy)methane (CEM) on myocardial response to ischemia
      was tested in rats. CEM was dermally applied for 3 days to F344/N male rats, at
      0, 100, 400, or 600 mg/kg/d. Subsequently, left ventricular sections were
      prepared from each rat heart. Part of the sections from each heart were exposed
      to 90 minutes of simulated ischemia, followed by 90 minutes of reoxygenation. The
      rest of the sections were continuously oxygenated. Mitochondrial activity was
      assessed in the sections by the MTT colorimetric assay, reflecting dehydrogenases
      redox activity. Myocardial toxicity occurred in response to 400 and 600 mg/kg,
      characterized by myofiber vacuoles, necrosis, and mononuclear infiltrates. The
      latter dose was lethal. In sections from rats treated with 400 mg/kg CEM, redox
      activity was decreased by 21% (p<0.01) in oxygenated conditions and by 45%
      (p<0.01) in ischemia-reoxygenation, compared to controls. Hearts of rats treated
      with 100 mg/kg/d CEM showed normal histology. Their mitochondrial activity did
      not differ from that of untreated rat hearts in oxygenated conditions. However,
      in ischemia-reoxygenation, their redox activity was significantly lower (by 46%,
      p<0.01) than that of untreated rat hearts. These results demonstrate that
      subtoxic dosage of a cardiotoxic agent may cause occult cardiotoxicity, reflected
      by impaired response to ischemia.

PMID- 17455087
TI  - Age- and sex-related differences in spontaneous hemorrhage and fibrosis of the
      pancreatic islets in Sprague-Dawley rats.
AB  - To elucidate the spontaneous occurrence of hemorrhage in the pancreatic islet,
      naive Crj:CD(SD)IGS rats were given a commercially available standard diet ad
      libitum over 20 weeks, and were sequentially examined. Islet hemorrhage was
      morphologically observed from 12 weeks of age, and its incidence was
      significantly higher in males than in females, with a wide distribution in all
      pancreatic lobes. The incidence (%) of affected islets to examined islets was
      increased with age. Hemorrhage was accompanied by brownish pigmentation, and
      reacted positively for iron by Prussian/Berlin blue staining. In 26 weeks old,
      most of the islets were dissected by dense fibrous tissue into small nests, and
      disarranged beta cells were detected by insulin immunostaining.
      Ultrastructurally, no apparent morphological change was seen in any islet
      endothelial cell, although blood leakage with migrated macrophages and dense
      collagen fibers was observed around the capillaries. In serum biochemistry of
      rats aged 26 weeks, the estradiol level in males with hemorrhage was
      significantly lower than that in males with non-hemorrhage, presumably suggesting
      the lack of capillary protective ability. Next, when rats were given a high
      fat/protein diet over 20 weeks to clarify whether it accelerated the frequency or
      timing of hemorrhage, its occurrence was essentially identical to that of the
      animals fed the standard diet. In conclusion, the onset of spontaneous islet
      hemorrhage was observed predominantly in aged males, resulting from the low
      estradiol level in serum.

PMID- 17455088
TI  - Spermatogenesis in the cynomolgus monkey (Macaca fascicularis): a practical guide
      for routine morphological staging.
AB  - The cynomolgus monkey (Macaca fascicularis) is widely used in regulatory toxicity
      studies. Especially in studies on male contraception, the male reproductive tract
      can be an important target system. The aim of the present paper is to describe a
      practical approach for morphological staging of spermatogenesis in routinely
      prepared paraffin sections. Results obtained using this approach could help to
      determine possible drug-related effects on spermatogenesis. As a guide to the
      investigators, photomicrographs of Bouin-fixed, paraffin-embedded and H&E or PAS
      stained sections from testis tissue are presented to illustrate the twelve
      successive morphological stages (cell associations) of normal spermatogenesis.
      Sexually immature or peripubertal monkeys sometimes are included in toxicity
      studies. Since the morphological features of the testes of such monkeys can be
      mistaken for treatment-related abnormalities, the morphologic characteristics of
      these testes are described and discussed briefly.

PMID- 17455089
TI  - Histopathology of rainbow trout exposed to sublethal concentrations of methiocarb
      or endosulfan.
AB  - Liver, spleen, trunk kidney, gills, and brain of rainbow trout (Oncorhynchus
      mykiss) were examined histologically after exposure to different concentrations
      of methiocarb (2.5 and 3.75 mg/L) or endosulfan (0.6 and 1.3 micro g/L) for 21
      days. Histological recovery was also studied by maintaining the pesticide-exposed
      fish in a freshwater system for an additional 30 d. Lesions were not evident in
      liver, kidney, spleen, or brain of fish exposed to either concentration of
      methiocarb for 21 d. Lesions were observed in gills, liver, spleen, and trunk
      kidney (but not brain) of rainbow trout exposed to either concentration of
      endosulfan. There was no concentration-related effect observed on the
      histopathological lesions. After 30 days of recovery, fish had no histological
      lesions in gills, kidney, spleen, liver, or brain. Therefore all the changes
      observed during exposure were reversible.

PMID- 17455090
TI  - Human heart glutamate receptors - implications for toxicology, food safety, and
      drug discovery.
AB  - Excitatory amino acids (EAAs) mediate their effects through the glutamate
      receptors (GluRs) in the brain. GluRs play an important role in the treatment of
      a variety of neuropsychiatric conditions and are central to the neurotoxicity of
      EAAs such as domoic and kainic acid. Unstained histological preparations of human
      heart tissues were used for the histopathological assessment, the anatomical
      identification of specific cardiac structures and the presence of the GluRs.
      Immunohistochemical stains with the biomarkers protein gene product (PGP 9.5) and
      the neurofilaments (NF 160 and NF 200) were used to identify neural structures
      and the components of the conducting system. Several subtypes of GluRs were
      differentially expressed and each had a specific distribution. In contrast to
      nonhuman primates, GluRs are more widely expressed in humans, where the working
      myocardium and the wall of blood vessels stained for GluRs. The immunolabelling
      was observed within the specialized structures of the conducting system,
      intramural nerves, and ganglia cells. These receptors may be involved in
      important cardiac functions such as contraction, rhythm, coronary circulation,
      and thus may be implicated in the pathobiology of some cardiac disease. The GluRs
      in the heart could be targets for the effects of excitatory compounds and is
      therefore an important consideration for the safety evaluation of foods and
      therapeutic products.

PMID- 17455091
TI  - Cardioprotective effect of oleanolic acid on isoproterenol-induced myocardial
      ischemia in rats.
AB  - This study was designed to investigate the protective effect of oleanolic acid
      (OA) against isoproterenol-induced myocardial ischemia in rat myocardium. Wistar
      strain rats were pretreated with OA (20, 40, and 60 mg/kg, s.c) for 7 days and
      then intoxicated with isoproterenol (ISO, 85 mg/kg, sc for 2 consecutive days).
      Heart were excised from the experimental animals and assessed for the activities
      of marker enzymes [alanine aminotransferase (ALT), aspartate aminotransferase
      (AST), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK)], the levels
      of lipid peroxide products [thiobarbituric acid reactive substances (TBARS),
      lipid hydroperoxides (HP) and conjugated dienes (CD)], myeloperoxidase (MPO),
      lipid profiles [total cholesterol (TC), free cholesterol, ester cholesterol,
      triglycerides (TG), free fatty acids (FFA) and phospholipids (PL)], and membrane
      bound ATPase enzymes (total ATPase, Na(+)K(+) ATPase, Ca(2 +) ATPase, and Mg(2 +)
      ATPase). Troponin T and I were estimated in plasma. Leakage of cardiac markers,
      elevated lipid peroxidation with increased lipid profiles and decreased
      activities of membrane-bound ATPase enzymes were confirmed the severe myocardial
      damage occurring as a consequence of isoproterenol-induced ischemia, and they
      also showed the significant improvement effected by oleanolic acid pretreatment.
      These findings provided evidence that oleanolic acid was found to be protecting
      rat myocardium against ischemic insult and the protective effect could attribute
      to its anti-oxidative, anti-hyperlipedemic, and anti-arrhythmic properties as
      well as its membrane-stabilizing action.

PMID- 17455092
TI  - Ultrastructural observations in a case of BK virus nephropathy with viruses in
      glomerular subepithelial humps.
AB  - BK virus nephropathy is a known cause of renal transplant dysfunction and
      failure. The disease is identified by examination of kidney biopsy tissue
      utilizing histopathological techniques. Ultrastructural examination of two
      glomeruli revealed pathology within one glomerulus. Glomerular basement membranes
      contained subepithelial humps of deposit-like material and BK viruses were
      identified within this material. Viruses were identified within intertubular
      capillaries. There was evidence of cytoplasmic clearance of viruses from the
      glomerular basement membrane by podocytes. The findings may be relevant to the
      investigation of hump formation and antigen clearance in BK virus nephropathy and
      postinfectious glomerulonephritis.

PMID- 17455093
TI  - Ultrastructural heterogeneity of gangliogliomas.
AB  - Gangliogliomas are rare brain tumors, composed of neuronal and glial cells mixed
      in a different proportion. The basic histopathological pattern of gangliogliomas
      is well recognized but the variable microscopic appearance still can pose a
      challenge to the neuropathologist. The authors reanalyzed their series of
      gangliogliomas in the files of two departments of neuropathology. All analyzed
      tumors fulfilled the WHO histological criteria of ganglioglioma. Seven tumors
      were examined by electron microscopy. The following ultrastructural features were
      graded: presence of dense-cored vesicles, synaptic vesicles, synapses and
      intermediate filaments, abundant basal membranes, dystrophic neurites, autophagic
      vacuoles, and multivesicular bodies. Most of the neoplastic neurons were large,
      polyglonal or oval with well-developed subcellular organelles, round nuclei, and
      prominent nucleoli. In most cases there were abundant dense core vesicles,
      observed in both the tumor cell bodies as well as in their processes. Synapses
      were typically observed. Intermediate filaments were abundant in all tumors. The
      most intriguing ultrastructural finding was abundant presence of autophagic
      vacuoles. In 4 cases, multivesicular bodies were observed. All of the tumors with
      multivesicular bodies also contained abundant autophagic vacuoles.

PMID- 17455094
TI  - Electron microscopy of chorionic villus samples for prenatal diagnosis of
      lysosomal storage disorders.
AB  - Some lysosomal storage disorders cause progressive prenatal accumulation of
      undegradable metabolites that manifest as membrane-bound vacuoles in endothelial
      cells, fibroblasts, and trophoblast, identifiable by electron microscopic
      examination of chorionic villus samples (CVS). There were 111 CVS, which had
      ultrastructural examination for suspected storage disorders at Great Ormond
      Street Hospital (1988-2005). There were 31 positive diagnoses, including glycogen
      storage disease type II, gangliosidosis type 1, mucopolysaccharidosis type 1, MPS
      not specified, Niemann-Pick type A, sialidosis/mucolipidosis type 1, neuronal
      ceroid lipofuscinoses (including variant forms), Wolman disease, sialic acid
      storage disease, and storage disease not specified. In most of these cases the
      indication was a previously affected individual. Seventy-seven cases showed no
      evidence of storage disease; 3 samples were inadequate for ultrastructural
      diagnosis. In selected cases, one-third of CVS may demonstrate distinctive
      ultrastructural features allowing prenatal diagnosis of a range of storage
      diseases.

PMID- 17455095
TI  - Ultrastructural characteristics of human mesenchymal stromal (stem) cells derived
      from bone marrow and term placenta.
AB  - Human mesenchymal stromal (stem) cells (hMSCs) isolated from adult bone marrow
      (BM-hMSCs) as well as amnion (AM-hMSCs) and chorion (CM-hMSCs) term placenta
      leaves were studied by transmission electron microscopy (TEM) to investigate
      their ultrastructural basic phenotype. At flow cytometry, the isolated cells
      showed a homogeneous expression of markers commonly used to identify hMSCs, i.e.,
      CD105, CD44, CD90, CD166, HLA-ABC positivities, and CD45, AC133, and HLA-DR
      negativities. However, TEM revealed subtle yet significant differences. BM-hMSCs
      had mesenchymal features with dilated cisternae of rough endoplasmic reticulum
      (rER) and peripheral collections of multiloculated clear blisters; this latter
      finding mostly representing complex foldings of the plasma membrane could be
      revelatory of the in situ cell arrangement in the niche microenvironment. Unlike
      BM-hMSCs, CM-hMSCs were more primitive and metabolically quiescent, their major
      features being the presence of rER stacks and large peripheral collections of
      unbound glycogen. AM-hMSCs showed a hybrid epithelial-mesenchymal ultrastructural
      phenotype; epithelial characters included non-intestinal-type surface microvilli,
      intracytoplasmic lumina lined with microvilli, and intercellular junctions;
      mesenchymal features included rER profiles, lipid droplets, and well-developed
      foci of contractile filaments with dense bodies. These features are consistent
      with the view that AM-hMSCs have a pluripotent potential. In conclusion, this
      study documents that ultrastructural differences exist among phenotypically
      similar hMSCs derived from human bone marrow and term placenta leaves; such
      differences could be revelatory of the hMSCs in vitro differentiation potential
      and may provide useful clues to attempt their in situ identification.

PMID- 17455096
TI  - Intracellular distribution of beta-catenin in human medulloblastoma cell lines
      with different degree of neuronal differentiation.
AB  - Gene mutations impairing the functions of the WNT signaling transduction pathway
      have been found in approximately 15% of human sporadic medulloblastomas. To
      understand the functional role of the WNT pathway in medulloblastoma, we have
      investigated the intracellular distribution of beta-catenin in a series of 17
      human medulloblastomas to correlate such expression with neuronal differentiation
      and in cultured cell models following functional silencing of the APC gene by
      small-interference RNA (siRNA). Transient siRNA transfection resulted in a 50%
      reduction of the APC gene product levels in both DAOY and D283MED cell lines. In
      the former, less-differentiated cell line, beta-catenin levels remained unchanged
      or were slightly reduced, but beta-catenin translocated in the nucleus following
      APC gene siRNA silencing. In contrast, in the more differentiated D283MED cells,
      beta-catenin levels increased about twofold while mainly maintaining the
      cytoplasmic and cell membrane localization. Cytoplasmic/nuclear localization of
      beta-catenin was present in 12 of 17 cases of medulloblastoma with a prevalent
      distribution in the classic, 6/7 cases, and large cell/anaplastic variant, 4/4
      cases. The nodular/desmoplastic lesions showed strongly positivity in the cell
      membrane mainly of intranodular cells with advanced neuronal differentiation.
      These observations support an important functional role of WNT/beta-catenin
      pathway in neuronal differentiation in medulloblastoma.

PMID- 17455097
TI  - Macrophagic myofasciitis in childhood: the role of scanning electron
      microscopy/energy-dispersive spectroscopy for diagnosis.
AB  - Macrophagic myofasciitis (MMF) is an inflammatory myopathy related to aluminum
      containing vaccines. Described in 1998, most cases were reported in adults, with
      only 22 cases being reported in children. Three children aged between 13 months
      and 3(1/2) years were investigated in our institution for neuromuscular symptoms.
      They underwent thorough clinical, familial, and laboratory investigations,
      electroneuromyography, muscle biopsy with transmission electron microscopy,
      scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS), and, in
      one case, brain magnetic resonance imaging. They had received regular
      immunizations. Two patients were hypotonic and one presented with myotonia.
      Muscle biopsy of all patients presented macrophagic infiltrates with
      intracytoplasmic aluminum content as revealed by SEM/EDS analysis. Their diverse
      clinical picture does not support a direct relationship between local morphologic
      findings and systemic symptoms. The atypical clinical presentation of these
      children may not result from the superposition of MMF upon a background systemic
      neuromyopathy, suggesting instead that they are two coincident and independent
      conditions. Although the finding of macrophage infiltrates in muscle tissue is
      not new, the identification of aluminum content is recent. The use of tissue
      sections for aluminum detection and mapping by SEM/EDS is conclusive for,
      diagnosis; it has not been reported previously in a pathology journal, to the
      authors' knowledge.

PMID- 17455098
TI  - Pulmonary lipomatous hemangiopericytoma: report of a rare tumor and comparison
      with solitary fibrous tumor.
AB  - Lipomatous hemangiopericytoma is a rare mesenchymal tumor showing areas of lipid
      containing cells admixed with a spindle-cell component. Like other
      hemangiopericytomas, it shows a similar vascular pattern to solitary fibrous
      tumor and, partly for this reason, it and other hemangiopericytomas have been
      subsumed into solitary fibrous tumor. The present study provides a comprehensive
      documentation of a single case of pulmonary lipomatous hemangiopericytoma of the
      lung, the first to be described at this site, and compares it with solitary
      fibrous tumor, in terms of clinical, histological, immunohistochemical,
      ultrastructural, and cytogenetic findings. Apart from the lipid-laden-cell
      component, pulmonary lipomatous hemangiopericytoma and solitary fibrous tumor
      were similar histologically. Bcl-2 was positive in both. CD34 was minimally
      expressed in pulmonary lipomatous hemangiopericytoma, which possessed some non
      descriptive intercellular junctions, a feature shared by solitary fibrous tumor,
      which was CD34 positive. However, one of the latter was rich in gap junctions, a
      feature consistent with strong connexin (Cx) 43 staining and the existence,
      hitherto unappreciated, of a CD34/Cx43-positive tumor cell network. In pulmonary
      lipomatous hemangiopericytoma, chromosomal deletions of 43-44, X, -Y were found.
      In solitary fibrous tumor, 46, XY, del(13)(q?) abnormalities and abnormalities
      involving chromosome 10 were frequently observed. These similarities and
      differences are discussed in the context of the currently favored diagnostic
      fusion of hemangiopericytoma and solitary fibrous tumor.

PMID- 17455100
TI  - Malignant mesothelioma with intracytoplasmic crystalline inclusions.
AB  - A 60-year-old female presented with a history of hoarseness, cough, chest pain,
      and dyspnea and a needle biopsy sample was submitted for histology. Light
      microscopy showed sheets of tumor cells with eosinophilic cytoplasm containing
      multiple crystals and eccentrically located nuclei. Electron microscopy showed
      large intracytoplasmic crystalloid inclusions. No crystalloid structures were
      found extracellularly. The tumor cells also had long slender microvilli and cell
      junctions, the features being consistent with a malignant epithelial
      mesothelioma. In the authors' experience this is a rare finding. The clinical
      information initially received was poor and electron microscopy was essential in
      making the correct diagnosis.

PMID- 17455099
TI  - Urethral stromal tumor with pacemaker cell phenotype.
AB  - Penile malignancies are rare in developed countries. The authors present a case
      of a penile urethral mesenchymal tumor occurring in a 51-year-old Caucasian male
      and displaying light microscopic, immunohistochemical, and ultrastructural
      features suggestive of a pacemaker cell type, combined with a lack of diagnostic
      features of any other established tumor category. The immunohistochemical profile
      was intensely positive for vimentin, PKC theta, and NSE and weakly positive to
      nonreactive for CD34 and smooth muscle actin, and entirely negative for CD117 (c
      kit), S-100, and other markers. C-kit and PDGFRA gene analysis showed no
      mutations. Electron microscopy revealed tumor cells with plentiful cytoplasm and
      cytoplasmic processes/filopodia, both filled with intermediate filaments and
      occasional solitary focal densities. There were also prominent smooth endoplasmic
      reticulum cisternae, caveolae, neurosecretory granules, particularly concentrated
      in cytoplasmic processes, and synaptic-type structures. Poorly formed basal
      lamina, gap junctions, and intercellular collagen aggregates, consistent with
      skeinoid-type fibers, were also noted. Interstitial cells with potential
      pacemaker function have been recently described in the lower urinary tract,
      including the urethra, and this tumor may be related to this cellular phenotype.

PMID- 17455101
TI  - Updated WFSBP Guidelines for the Biological Treatment of Unipolar Depressive
      Disorders in Primary Care.

PMID- 17455103
TI  - Does age at onset support a dimensional relationship between Bipolar II disorder
      and major depressive disorder?
AB  - The current categorical splitting of bipolar and depressive disorders has been
      questioned. Age at onset is an important variable used to support such a
      division. Study aim was to assess the distribution of age at onset between
      bipolar II disorder (BP-II) and major depressive disorder (MDD), and onset age
      bipolar family history, onset age-BP-II diagnosis dose-response relationships. No
      bi-modal distribution and no presence of dose-response relationships would not
      support a categorical distinction between BP-II and MDD. Consecutive 389 BP-II
      and 261 MDD major depressive episode (MDE) outpatients were interviewed with the
      DSM-IV Structured Clinical Interview and the Family History Screen, by a mood
      specialist psychiatrist in a private practice. Age at onset was defined as age at
      onset of the first MDE. Distribution of age at onset between BP-II and MDD was
      studied by Kernel density estimate and histogram methods, dose-response
      relationships by ROC analysis. BP-II, versus MDD, had significantly lower age at
      onset, more recurrences, and more bipolar family history. Kernel density estimate
      and histogram distributions of age at onset showed no bi-modality. Likelihood
      ratios between age at onset and bipolar family history loading, and between age
      at onset and BP-II diagnosis, showed dose-response relationships. The bi-modality
      and dose-response approaches, versus classic diagnostic validators, seem to
      support a dimensional relationship between BP-II and MDD.

PMID- 17455102
TI  - World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for
      Biological Treatment of Unipolar Depressive Disorders in Primary Care.
AB  - These practical guidelines for the biological treatment of unipolar depressive
      disorders in primary care settings were developed by an international Task Force
      of the World Federation of Societies of Biological Psychiatry (WFSBP). They
      embody the results of a systematic review of all available clinical and
      scientific evidence pertaining to the treatment of unipolar depressive disorders
      and offer practical recommendations for general practitioners encountering
      patients with these conditions. The guidelines cover disease definition,
      classification, epidemiology and course of unipolar depressive disorders, and the
      principles of management in the acute, continuation and maintenance phase. They
      deal primarily with biological treatment (including antidepressants, other
      psychopharmacological and hormonal medications, electroconvulsive therapy, light
      therapy).

PMID- 17455104
TI  - Mirtazapine monotherapy versus combination therapy with mirtazapine and
      aripiprazole in depressed patients without psychotic features: a 4-week open
      label parallel-group study.
AB  - BACKGROUND: There is preliminary evidence that the atypical antipsychotic
      aripiprazole, which is a partial agonist at D(2) and 5-HT(1A) receptors and a
      potent antagonist at 5-HT(2A) receptors, may be useful as an augmentation
      strategy in treatment-resistant depression. METHOD: In this 4-week open-label non
      randomized parallel-group study, the safety and efficacy of aripiprazole as add
      on treatment strategy in patients suffering from non-delusional depression was
      investigated. Forty drug-free depressed inpatients without psychotic symptoms (13
      men, 27 women), suffering from a major depressive episode or bipolar disorder,
      depressive state (DSM-IV criteria), were included in the study. The patients were
      treated either with mirtazapine monotherapy (45 mg/day) or combination therapy
      (mirtazapine 45 mg/day plus aripiprazole 15 mg/day) for 4 weeks. Safety and
      efficacy were assessed weekly using the Hamilton Depression Rating Scale, the
      Simpson-Angus Scale and the Barnes Akathisia Scale. RESULTS: Mirtazapine
      monotherapy and combined treatment with mirtazapine and aripiprazole showed
      comparable antidepressant effects as assessed at the endpoint of the study
      period. However, additional administration of aripiprazole accelerated the onset
      of antidepressant action in patients suffering from treatment-resistant
      depression. Additive use of aripiprazole reduced the mirtazapine-induced increase
      in the body mass index. Moreover, mirtazapine had favourable effects on
      aripiprazole-induced akathisia. No other extrapyramidal side effects were seen in
      the combination therapy group. CONCLUSION: Combined therapy with mirtazapine and
      aripiprazole is a safe and well-tolerated treatment option which may be useful
      especially in treatment-resistant depression. Double-blind controlled studies are
      needed to further explore the efficacy and safety of aripiprazole in depressed
      patients.

PMID- 17455105
TI  - Clinical improvement in a case of frontotemporal dementia under aripiprazole
      treatment corresponds to partial recovery of disturbed frontal glucose
      metabolism.
AB  - Frontotemporal dementia (FTD) is increasingly recognized as an important type of
      degenerative dementia but satisfactory pharmacological treatment has not yet been
      established. We examined the clinical effects of aripiprazole, a new
      antipsychotic with partial agonistic properties at serotonin 5-HT(1A) and
      dopamine D(2) receptors, in parallel with cortical glucose metabolism changes. We
      conducted a follow-up investigation of clinical status and (18)F-fluoro-2-deoxy-d
      glucose (FDG) positron emission tomography (PET) in a 73-year-old male patient
      with FTD over a 13-month period. Under conventional drug treatment during the
      first 12 months a marked increase in dementia symptoms was observed. Frontal lobe
      glucose metabolism clearly decreased during this time period. Under consecutive
      treatment with aripiprazole a significant and stable improvement of clinical
      symptoms could be registered, while disturbed frontal glucose metabolism
      increased significantly. According to this case experience, further
      investigations should be undertaken to ascertain whether aripiprazole or other
      atypical antipsychotics with properties to improve impaired dopaminergic
      transmission in frontal brain regions could qualify for therapy of FTD.

PMID- 17455106
TI  - Autistic disorder and 22q11.2 duplication.
AB  - Although several reports have described the co-occurrence of autism in subjects
      with chromosome 22 abnormalities including trisomy 22, translocation 20/22,
      22q11.2 deletion, ring chromosome 22, and 22q13.3 deletion, there is no report
      with 22q11.2 duplication. We report a 9-year-old girl, referred to our department
      for her behavioural problems and language delay. She was diagnosed with autistic
      disorder according to DSM-IV criteria. Because of her dysmorphic characteristics
      comprising narrow face, narrow forehead, mandibular prognathism, synophrys, and
      operated cleft palate and cardiac problems, she had gone under cytogenetic
      analysis. Although she was ascertained as suspected velocardiofacial syndrome
      (VCFS), the duplication of 22q11.2 was detected by interphase fluorescence in
      situ hybridization. Previous reports on the psychiatric aspects of 22q11.2
      duplication have shown the existence of hyperactivity, learning disability,
      speech problems, and aggressive behaviours but not autism. Moreover, the lack of
      reports of co-occurrence of autism and 22q11.2 duplication may be related to
      paucity as a result of technical problems.

PMID- 17455107
TI  - Comments on the report of neuroleptic malignant syndrome induced by ziprasidone.

PMID- 17455109
TI  - Functional characterization of two novel CYP2C19 variants (CYP2C19*18 and
      CYP2C19*19) found in a Japanese population.
AB  - Cytochrome P450 2C19 (CYP2C19) plays an important role in the metabolism of a
      wide range of therapeutic drugs and exhibits genetic polymorphism with
      interindividual differences in metabolic activity. We have previously described
      two CYP2C19 allelic variants, namely CYP2C19*18 and CYP2C19*19 with
      Arg329His/Ile331Val and Ser51Gly/Ile331Val substitutions, respectively. In order
      to investigate precisely the effect of amino acid substitutions on CYP2C19
      function, CYP2C19 proteins of the wild-type (CYP2C19.1B having Ile331Val) and
      variants (CYP2C19.18 and CYP2C19.19) were heterologously expressed in yeast
      cells, and their S-mephenytoin 4'-hydroxylation activities were determined. The
      K(m) value of CYP2C19.19 for S-mephenytoin 4'-hydroxylation was significantly
      higher (3.0-fold) than that of CYP2C19.1B. Although no significant differences in
      V(max) values on the basis of microsomal and functional CYP protein levels were
      observed between CYP2C19.1B and CYP2C19.19, the V(max)/K(m) values of CYP2C19.19
      were significantly reduced to 29-47% of CYP2C19.1B. By contrast, the K(m), V(max)
      or V(max)/K(m) values of CYP2C19.18 were similar to those of CYP2C19.1B. These
      results suggest that Ser51Gly substitution in CYP2C19.19 decreases the affinity
      toward S-mephenytoin of CYP2C19 enzyme, and imply that the genetic polymorphism
      of CYP2C19*19 also causes variations in the clinical response to drugs
      metabolized by CYP2C19.

PMID- 17455110
TI  - Effects of N-terminal modification of recombinant human cytochrome P450 1A2 on
      catalytic activity.
AB  - 1. The high-level expression of mammalian cytochrome P450 in bacteria usually
      requires modification of the amino-terminal region of the enzyme. The effect of
      altering amino acids in the N-terminus of human recombinant CYP1A2 on its
      catalytic activity was investigated herein. 2. Rates of 7-ethoxyresorufin O
      deethylation by CYP1A2a (a form made by altering the amino acids LLL of CYP1A2 to
      RER at positions 3-5) in reconstituted systems were significantly low compared
      with those of other CYP1A2 N-terminal variants at a low ratio of cytochrome P450
      to NADPH-cytochrome P450 reductase, but not at higher reductase concentrations.
      3. CYP1A2a-dependent ethoxyresorufin O-deethylase activity in a cumene
      hydroperoxide-supported system was approximately 2-fold higher than other CYP1A2
      N-terminal variants. 4. Our results suggest that modification of three N-terminal
      amino acids in CYP1A2 alters the interaction between CYP1A2 and the reductase in
      reconstituted phospholipid vesicles and in the bicistronic membranes.

PMID- 17455111
TI  - Decreased PXR and CAR inhibit transporter and CYP mRNA Levels in the liver and
      intestine of mice with collagen-induced arthritis.
AB  - Nuclear receptors, such as pregnane X receptor (PXR) and constitutive androstane
      receptor (CAR), regulate the transcription of transporters and cytochrome P450s
      (CYPs). We investigated whether quantitative and functional changes in PXR and
      CAR affected the transporters and CYPs in a mouse model of chronic arthritis. The
      mRNA levels of PXR were significantly decreased in the intestine of mice with
      collagen-induced arthritis (CIA) compared with control mice. The mRNA levels of
      CAR were significantly decreased in both the liver and intestine of CIA mice. The
      mRNA levels of Mdr1a/1b, Mrp3, BCRP and Cyp2b10 were decreased in the liver of
      CIA mice, while little change in the mRNA levels was observed for Cyp3a11 in the
      liver and the transporters in the intestine. Taken together, the present results
      reveal that the effects of CAR mRNA suppression on the regulation of transporters
      and CYPs differ between the liver and intestine in chronic arthritis.

PMID- 17455113
TI  - Inhibition of human organic anion transporter 3 mediated pravastatin transport by
      gemfibrozil and the metabolites in humans.
AB  - Coadministration of gemfibrozil (600 mg, b.i.d., 3 days) with pravastatin (40
      mg/day) decreased the renal clearance of pravastatin by approximately 40% in
      healthy volunteers. To investigate the mechanism of this drug-drug interaction in
      the renal excretion process, we undertook an uptake study of pravastatin using
      human organic anion transporters (hOATs)-expressing S2 cells. hOAT3 and hOAT4
      transported pravastatin in a saturatable manner with Michaelis--Menten constants
      of 27.7 microM and 257 microM respectively. On the other hand, hOAT1 and hOAT2
      did not transport pravastatin. Gemfibrozil and its glucuronide and carboxylic
      metabolite forms inhibited the uptake of pravastatin by hOAT3 with IC(50) values
      of 6.8 microM, 19.7 microM and 5.4 microM, respectively. Considering the plasma
      concentrations of gemfibrozil and its metabolites in humans, the inhibition of
      hOAT3-mediated pravastatin transport by gemfibrozil and its metabolites would
      lead to a decrease in the renal clearance of pravastatin in clinical settings.

PMID- 17455112
TI  - Role of ATP-binding cassette drug transporters in the intestinal absorption of
      tanshinone IIB, one of the major active diterpenoids from the root of Salvia
      miltiorrhiza.
AB  - There is an increasing use of herbal medicines worldwide, and the extracts from
      the root of Salvia miltiorrhiza are widely used in the treatment of angina and
      stroke. In this study, we investigated the mechanism for the intestinal
      absorption of tanshinone IIB (TSB), a major constituent of S. miltiorrhiza. The
      oral bioavailability of TSB was about 3% in rats with less proportional increase
      in its maximum plasma concentration (C(max)) and area under the plasma
      concentration-time curve (AUC) with increasing dosage. The time to C(max)
      (T(max)) was prolonged at higher oral dosage. In a single pass rat intestinal
      perfusion model, the permeability coefficients (P(app)) based on TSB
      disappearance from the lumen (P(lumen)) were 6.2- to 7.2-fold higher (p < 0.01)
      than those based on drug appearance in mesenteric venous blood (P(blood)). The
      uptake and efflux of TSB in Caco-2 cells were also significantly altered in the
      presence of an inhibitor for P-glycoprotein (PgP) or for multi-drug resistance
      associated protein (MRP1/2). TSB transport from the apical (AP) to basolateral
      (BL) side in Caco-2 monolayers was 3.3- to 5.7-fold lower than that from BL to AP
      side, but this polarized transport was attenuated by co-incubation of PgP or
      MRP1/2 inhibitors. The P(app) values of TSB in the BL-AP direction were
      significantly higher in MDCKII cells over-expressing MDR1 or MRP1, but not in
      cells over-expressing MRP2-5, as compared with the wild-type cells. The plasma
      AUC(0-24hr) in mdr1a and mrp1 gene-deficient mice was 10.2- to 1.7-fold higher
      than that in the wild-type mice. Furthermore, TSB significantly inhibited the
      uptake of digoxin and vinblastine in membrane vesicles containing PgP or MRP1.
      TSB also moderately stimulated PgP ATPase activity. Taken collectively, our
      findings indicate that TSB is a substrate for PgP and MRP1 and that drug
      resistance to TSB therapy and drug interactions may occur through PgP and MRP1
      modulation.

PMID- 17455114
TI  - [14C]bis(2-chloroethoxy)methane: comparative absorption, distribution, metabolism
      and excretion in rats and mice.
AB  - bis(2-Chloroethoxy)methane (BCM) is used primarily as a precursor in the
      synthesis of polysulfide elastomers. After administration of [(14)C]BCM,
      radioactivity is readily absorbed from the gastrointestinal tract and moderately
      absorbed through skin. Following absorption, BCM-derived radioactivity is rapidly
      distributed to all tissues, rapidly metabolized and excreted primarily in urine.
      Minimal effects of sex, species or dose in the range studied (0.1-10 mg kg(-1))
      were observed on the fate of BCM in rats and mice after all routes of
      administration. The major metabolite (about 40% of the dose) of BCM in rat was
      isolated and identified as thiodiglycolic acid (TDGA) indicating that the ether
      linkage of BCM is cleaved to form 2-chloroethyl fragments that may be further
      metabolized to 2-chloracetaldehyde, conjugated with glutathione and the latter
      subsequently metabolized to TDGA. 2-chloroacetaldehyde has also been shown to be
      cardiotoxic, possibly accounting for BCM cardiotoxicity observed in repeated dose
      studies.

PMID- 17455115
TI  - Comparison of cerebral pharmacokinetics of buprenorphine and norbuprenorphine in
      an in vivo sheep model.
AB  - The pharmacokinetics and time course of blood-brain equilibration of
      buprenorphine (BUP) and norbuprenorphine (norBUP) in sheep were characterized.
      Sheep were administered 0.04 mg kg(-1) BUP or 0.6 mg kg(-1) norBUP as 4-min i.v.
      infusions. The cerebral kinetics were inferred from arterio-sagittal sinus
      concentration gradients and changes in cerebral blood flow. These data were
      fitted to physiologically based pharmacokinetic models. BUP cerebral kinetics
      were best described by a membrane-limited model with a large equilibration delay
      (half-life of 20 min) between brain and blood due to intermediate permeability
      (47 ml min(-1)) and a large cerebral distribution volume (595 ml). Significant
      limitation in permeability (6 ml min(-1)) characterized the cerebral kinetics of
      norBUP with a cerebral distribution volume (157 ml) giving a blood-brain
      equilibration half-life (21 min) similar to that for BUP. The logD of BUP and
      norBUP were 3.93 +/- 0.08 and 1.18 +/- 0.04 (mean +/- SD), respectively. Both
      compounds revealed slow cerebral equilibration with variations in degree of
      permeability and distribution volume reflecting the difference in lipophilicity.
      It is possible that norBUP contributes to the central effects seen after chronic
      BUP administration as this study demonstrated its entry into the brain.

PMID- 17455116
TI  - Laboratory 20-km cycle time trial reproducibility.
AB  - This study evaluated the reproducibility of laboratory based 20-km time trials in
      well trained versus recreational cyclists. Eighteen cyclists (age = 34 +/- 8 yrs;
      body mass index = 23.1 +/- 2.2 kg/m (2); VO(2max) = 4.19 +/- 0.65 L/min)
      completed three 20-km time trials over a month on a Velotron cycle ergometer.
      Average power output (PO) (W), speed, and heart rate (HR) were significantly
      lower in the first time trial compared to the second and third time trial. The
      coefficients of variation (CV) between the second and third trial of the top
      eight performers for average PO, time to completion, and speed were 1.2 %, 0.6 %,
      0.5 %, respectively, compared to 4.8 %, 2.0 %, and 2.3 % for the bottom ten. In
      addition, the average HR, VO(2), and percentage of VO(2max) were similar between
      trials. This study demonstrated that (1) a familiarization session improves the
      reliability of the measurements (i.e., average PO, time to completion and speed),
      and (2) the CV was much smaller for the best performers.

PMID- 17455117
TI  - Impact of exercise capacity on myocardial high-energy phosphate metabolism.
AB  - 31-Phosphorous magnetic resonance spectroscopy (31P MRS) is a unique tool to
      investigate IN VIVO high-energy phosphates (HEP) in the human heart. We
      hypothesized that physical capacity may be associated with myocardial HEP status.
      Healthy, male volunteers (n = 105, mean age 51 +/- 7 years) underwent bicycle
      ergometry with a stepwise increasing workload to determine maximal working
      capacity (MWC). Heart rate (HR) and blood pressure (BP) were measured
      continuously during exercise and 4 minutes of recovery. Further 31-Phosphorous 2
      dimensional chemical shift imaging (31P 2D CSI) MRS was performed to assess
      myocardial HEP metabolism by determining phosphocreatinine to beta-ATP ratios
      (PCr/b-ATP) using a 1.5 tesla scanner. Volunteers with MWC > 230 Watt had
      significantly higher PCr/b-ATP ratios than those with MWC < 200 Watt (1.93 +/-
      0.36 vs. 1.59 +/- 0.35; p < 0.001). Additionally, those with a recovery systolic
      (S)BP < 195 mmHg had significantly higher ratios than those with a recovery SBP >
      195 mmHg (1.74 +/- 0.3 vs. 1.51 +/- 0.2; p < 0.05). We observed a linear
      correlation between the PCr/b-ATP ratio and MWC (r = 0.411; p < 0.001) and
      recovery SBP (r = - 0.290; p < 0.01). After statistical correction for age, these
      correlations remained significant. In this study, we observed a correlation of
      parameters of physical fitness determined by bicycle exercise testing and cardiac
      PCr/b-ATP ratios.

PMID- 17455118
TI  - Heart rate and blood lactate during official female motorcycling competitions.
AB  - The aim of this study was to investigate the physiological load of free practices
      (F), qualifying sessions (Q), and official races (R) of motorcycling
      competitions. Twenty-six female riders (age: 30.8 +/- 6.1 yrs) participated in
      this study. Anthropometric and strength evaluations were performed. Subject's
      heart rate (HR) was continuously recorded during three periods (5-minute Pre,
      Ride, and 5-minute Post) of the F, Q, and R phases of competitions. Blood lactate
      concentrations (La) were determined at rest and after riding. Riders had 56.5 +/-
      6.7 kg of body mass, 164 +/- 4 cm of height, 21.6 +/- 4.4 % of body fat, and a
      BMI of 20.9 +/- 2.3 kg . (m (2)) (-1). Significant handgrip differences were
      found between the preferred (307 +/- 32 n) and non-preferred (281 +/- 47 N)
      limbs. During riding, frequency of occurrence of HR >or= 90 % HR (max) was 67 %
      in F, 74 % in Q, and 83 % in R. La after ridings (4.8 +/- 2.6 mmol . l (-1)) was
      two-folds (p < 0.05) the basal values (2.2 +/- 0.5 mmol . l (-1)), independently
      from the competition phases. The present HR and La data show that female road
      race motorcycling imposes a very intensive physical strain to the riders who need
      to control their motorbikes while performing frequent accelerations and
      decelerations.

PMID- 17455119
TI  - Increased cx43 and angiogenesis in exercised mouse hearts.
AB  - Several studies focused on the macroscopic architecture of increased cardiac wall
      induced by exercise training. Our goal was to evaluate myocardiocyte,
      interstitial and vascular component, and connexin-43 expression in endurance
      trained mouse hearts. Sixty-three 10-week-old male Swiss mice were divided into
      four sedentary groups (C0, C15, C30 and C45) and three groups exercised
      respectively for 15 (T15-D; running intensity [RI]: 3.18 m/min; running duration
      [RD]: 75 min/first week and 150 min/second week), 30 (T30-D; RI: 3.96 m/min; RD:
      150 min/third week and 225 min/fourth week) and 45 days (T45-D; RI: 3.96 m/min
      and 4.8 m/min, respectively for the fifth and sixth week; RD: 300 min) on a
      treadmill. Morphometric analyses were performed to quantify myocardiocyte size
      and number, and the capillary and interstitial connective tissue (ICT) area. We
      assessed the expression of ventricle myosin light chain-II, vimentin and connexin
      43 by western blot analyses. Our results showed a hypertrophy of the
      interventricular septum and left ventricle in T30-D and T45-D mice that was not
      due to variations in myofibrillar content, myocardiocyte size and number, or ICT
      quantity but to a significant increase in the capillary area. The microvascular
      remodeling was associated with vimentin increased expression in ICT cells and
      connexin-43 upregulation. The first phenomenon might be related to an enhanced
      request of remodeling and growth factors; the second suggests a new role of
      connexin-43 in cardiac angiogenesis.

PMID- 17455120
TI  - Red cell and core temperature in spelunking.
AB  - Alpine spelunking is practiced in darkness, isolation, cold and high humidity. In
      this paper we study the acute haematological effects of prolonged strenuous
      activity in five spelunkers who spent about 20 hours in a 700-meter deep cave
      without resting much or sleeping. On four occasions, we measured their red cell
      counts, haemoglobin, mean corpuscular volume and percentage changes of plasma
      volume. We also measured their rectal temperature to estimate, in the limits of
      this parameter, thermoregulatory response. After the spelunkers descended 5 hours
      to the bottom of the cave, we detected, in all of them, a significant increase in
      red cell counts and haemoglobin and a drop in mean corpuscular volume and plasma
      volume. The day after recovery, we found a significant drop in all red cell
      parameters and a rise in plasma volumes. Rectal temperatures peaked at the exit.
      These findings suggest that alpine spelunking induces an initial
      haemoconcentration (bottom of the cave) followed by a haemodilution (the day
      after recovery). Sport anaemia was not detected. The rise of rectal temperature
      suggests that spelunking is a very strenuous sport with possible transpiration
      problems.

PMID- 17455121
TI  - Effects of strength training and reduced training on functional performance and
      metabolic health indicators in middle-aged men.
AB  - Changes in muscular fitness and metabolic health indicators were examined in 22
      men (57.9 +/- 6.6 years, BMI 24.5 +/- 2.6 kg/m (2)) and 21 control men (58.2 +/-
      6.1 years, BMI 25.4 +/- 2.8 kg/m (2)) during two consecutive 21-week periods: 1)
      whole body progressive strength training (ST: twice a week), and 2) continued
      reduced training (CRT: 3 ST sessions/2 weeks, n = 17 + 17). After the 21-week ST
      period, maximal strength of leg extensors increased in the ST group by 19.6 +/-
      7.6 % vs. 2.8 +/- 4.4 % (p < 0.001) and also 10-m walking time and 10-step stair
      climbing time shortened by - 17.2 +/- 7.6 % vs. 4.1 +/- 3.9 % (p < 0.01) and by -
      8.2 +/- 6.8 % vs. - 3.0 +/- 6.8 % (p < 0.05) compared to the controls. Systolic
      blood pressure (BP) decreased in the ST group by - 4.4 +/- 6.7 % vs. 1.3 +/- 9.5
      % (p < 0.05) compared to the controls after the ST period. Muscle strength as
      well as walking and stair-climbing times remained the same during the CRT.
      However, the changes in diastolic BP (- 8.9 +/- 8.7 % vs. - 1.0 +/- 6.6 %, p <
      0.05) and fasting blood glucose concentrations (0.1 +/- 0.4 mmol/L vs. 0.3 +/-
      0.4 mmol/L, p < 0.05) differed between the ST and control groups after the whole
      42-week study period. Strength training has positive health effects in aging men
      by increasing maximal strength and functional performance and by decreasing
      resting blood pressure and high-intensity reduced strength training can maintain
      these health benefits.

PMID- 17455122
TI  - The type and intensity of exercise have independent and additive effects on bone
      mineral density.
AB  - Previous research on the effects of running and swimming on areal bone mineral
      density (aBMD) is inconclusive. This study examined the putative roles of the
      type and intensity of exercise in this respect, by measuring aBMD (adjusted for
      age, weight, and height) of the total body and of various subregions in 52 males
      aged 17 - 30 yr (21 runners, 16 swimmers, 15 controls). The athletes were
      competing at either long-distance ("endurance", n = 17) or short-distance
      ("sprint", n = 20) events. Compared with controls, runners had significantly
      higher leg aBMD (+ 6.7 %, p < 0.05), while swimmers had significantly lower leg
      and total body aBMD (- 9.8 % and - 7.0 %, respectively, p < 0.05). Endurance
      athletes had significantly lower total body aBMD than controls (- 4.9 %, p <
      0.05). Sprint athletes did not differ significantly from controls at any site,
      but they had significantly higher aBMD than endurance athletes throughout the
      skeleton (p < 0.05). Compared with controls, endurance swimmers had significantly
      lower aBMD at the legs and total body (- 14.8 % and - 10.4 %, respectively, p <
      0.05), while sprint runners had significantly higher values for the legs, trunk,
      and total body (+ 8.0 %, + 10.0 %, and + 6.3 %, respectively, p < 0.05). Sprint
      swimmers and endurance runners did not differ from controls at any site or the
      total body. These results suggest that the type and intensity of exercise have
      independent and additive effects on bone density.

PMID- 17455123
TI  - Effect of soccer shoe cleats on knee joint loads.
AB  - Noncontact injuries frequently occur during soccer matches and training. The
      purpose of this study was to examine the influences of different soccer shoe
      studs to kinematic, kinetic and electromyographic parameters in the knee joint.
      Six male soccer players performed complex turning movements (180 degrees ) with
      bladed and round studded soccer shoes. Ground reaction forces, 3-D kinematics and
      electromyographic activity of the lower leg muscles were recorded. Calculated
      external knee joint moments were similar with both stud configurations, although
      there was a trend towards increased vertical and anterior-posterior ground
      reaction forces with blades. Electromyography evidenced significantly higher
      activation of m. quadriceps femoris (p = 0.02) with round studs during initial
      phase of stance. In conclusion, comparison of soccer shoes with round and bladed
      studs showed no significant differences in externally applied knee joint loads
      during a complex injury related movement. The significant increased activation of
      m. quadriceps femoris with round studs during the critical weight acceptance can
      be associated with an additional internal load on the anterior cruciate ligament.
      Therefore, results revealed no higher risk of getting noncontact knee joint
      injuries with bladed soccer shoes.

PMID- 17455124
TI  - Lisfranc injury in a national hockey league player: a case report.
AB  - Tarsometatarsal joint dislocations and fracture-dislocations are uncommon
      injuries most frequently resulting from high-energy trauma as encountered in
      crush injuries, falls, and motor vehicle accidents. Although less common in
      athletes, this injury is being recognized with greater frequency and may carry a
      poor prognosis for return to high levels of competition. These injuries present a
      considerable challenge to orthopedic surgeons caring for athletes because of the
      prolonged period of recovery often required [ 1,2,5,6,12]. The literature
      contains descriptions of this injury in football players, gymnasts, tennis
      players, and track and field athletes [2,5,9]. To our knowledge, no report of
      such a Lisfranc injury to a hockey player has been described. This is a case
      report of a National Hockey League player that sustained a Lisfranc injury
      requiring surgical stabilization, but was able to return to elite hockey play.

PMID- 17455133
TI  - [Studies of leakage measurements of automatic CPAP-devices].
AB  - INTRODUCTION: An effective CPAP-treatment is only possible, if greater mask-and
      mouth leakages are prevented. In the case of greater leakages the CPAP decreases
      and the flow induces side effects as rhinitis and conjunctivitis. In addition to
      mask-and mouth leakages there exists a leakage through the exhaust valve of the
      mask which is necessary to avoid CO2-rebreathing. This leakage changes are
      dependent on the pressure. In many automatic CPAP devices the hard- and software
      registers the leakage in parallel with the pressure variations. However it is
      unclear which leakages are considered. We analysed therefore the signal of the
      leakage of 4 automatic CPAP-devices concerning following questions: Does the
      leakage measurement of the devices correspond with the pneumotachographically
      measured flow. How is the leakage of the mask exhaust valve taken into account.
      METHOD: We simulated normal breathing with a mechanical ventilator. The
      respective device was connected by a y-piece with a 5 mm aperture (leakage). With
      an external flow analyser the flow of the leakage was registered and compared
      with the flow measured by the automatic CPAP-device. RESULTS: The flow of the
      devices A to C differed during 10 mbar CPAP from the value of the flow analyser
      by 5.0 %, 4.3 % and 11.3 %. The software of device D subtracts the leakage
      through the mask exhaust valve so that the indicated leakage corresponds with the
      mouth and mask leakage. CONCLUSION: The leakage was sufficiently well recorded by
      the tested automatic devices. When evaluating the leakage signal the flow through
      the mask exhaust valve should be taken into account.

PMID- 17455134
TI  - [Latent tuberculosis infection in healthcare workers--evaluation of an Interferon
      gamma release assay].
AB  - INTRODUCTION: The Interferon-gamma release assay (IGRA) is a promising
      alternative to the tuberculin skin test (TST) for the diagnosis of latent
      tuberculosis infection (LTBI). But so far only limited experience is available
      regarding the performance of these IGRAs especially in occupational medicine when
      used for screening healthcare workers (HCW). METHOD: In an ongoing study
      employees of three German hospitals are screened for LTBI using the TST Mendel
      Mantoux and the IGRA (QuantiFERON-TB Gold in Tube) simultaneously. Information on
      earlier tests which had been performed with the multipuncture tests were obtained
      by interview. Risk factors for a positive test result were calculated using
      multivariate logistic regression. RESULTS: The analysis comprises 161 employees
      for whom information on all the tests - multipuncture test, TST Mendel-Mantoux
      and IGRA were available. The multipuncture test was positive in 34.8 %, the TST
      Mendel-Mantoux in 26.7 % and the IGRA in 12.4 % of the participants. When
      adjusting for the proportion of positive test results caused by cross-reaction
      with BCG vaccination, the prevalence of LTBI reduces to 18.8 % in the
      multipuncture test and 19.2 % in the TST Mendel-Mantoux. The Test results of the
      IGRA were positively correlated with age while the results of the two in-vivo
      tests were not. DISCUSSION: The multipuncture test and the TST Mendel-Mantoux
      overestimate the prevalence of LTBI in HCW. A positive result in the TST should
      be verified by the IGRA before any further actions are recommended. A larger data
      base is needed in order to confirm that the IGRA is more sensitive in diagnosing
      a LTBI than the skin tests.

PMID- 17455135
TI  - [Diagnosis of nosocomial pneumonia: noninvasive but not undirected].

PMID- 17455136
TI  - [ATRA-syndrome].

PMID- 17455137
TI  - [Automatic positive airway pressure in titration and treatment of the obstructive
      sleep apnea syndrome].
AB  - Although continuous airway pressure therapy (CPAP) represents the standard
      treatment for obstructive sleep apnea syndrome (OSAS) auto-adjusting CPAP (APAP)
      devices were developed which adapt the treatment pressure to the actual
      requirement of the patients. The aim of automatic CPAP therapy is to improve the
      patients' acceptance of positive pressure treatment. The devices react to
      respiratory flow, flattening of the inspiratory flow contour, snoring, generator
      speed or the upper airway impedance. In recent years several studies showed that
      auto CPAP effectively treats respiratory disturbances, improves sleep profile and
      the self-assessment of the patients equally as good as the gold standard constant
      CPAP. Moreover, APAP reduces the treatment pressure substantially. Although an
      improvement of the patient's compliance has not consistently been proven, most
      patients prefer APAP versus constant CPAP. APAP devices use different algorithms
      depending on the primary purpose of the application. Therefore, a clear
      distinction between automatic titration and treatment is of major relevance.
      While titration devices aim at the finding of one single pressure which is fixed
      to a constant CPAP device, automatic treatment means the chronic use of APAP at
      home for optimal adaptation of the treatment pressure to the actual requirements
      of the patient. A high constant CPAP level, huge pressure variability,
      insufficient compliance with constant CPAP may be indications for APAP treatment.
      The main reason for automatic titration is the standardisation of the initiation
      process.

PMID- 17455138
TI  - [Rehabilitation of patients with chronic obstructive pulmonary disease (COPD). S2
      guideline of the German Society for Pneumology and Respiratory Medicine and the
      German Society for Rehabilitation Science (RGRW)].

PMID- 17455139
TI  - [Mechanical ventilation of acute lung injury].
AB  - Acute lung injury (ALI) is of paramount importance for modern intensive care
      since it is one of the most frequent conditions necessitating admission to an
      ICU. ALI is characterised by severe life threatening hypoxemia which is based on
      ventilation perfusion mismatching within the lung. This is mostly resulting from
      atelectasis formation due to primary or secondary inflammation of lung tissue.
      Many studies showed that this inflammatory process is not restricted to the
      respiratory system but might result in non pulmonary organ failure and
      hemodynamic compromise as well. Mechanical ventilation is considered the hallmark
      treatment for ALI patients aimed to recruit lung tissue and thereby reverse
      hypoxemia without causing additional lung injury potentially resulting from
      overdistention or cycling collapse during expiration. Scientific evidence shows
      us that prevention of ventilator induced lung injury by protective ventilation
      with reduced tidal volumes is resulting in better clinical outcomes. Moreover,
      different technologies and adjunctive therapies have been suggested based on
      their pathophysiology. All these treatment options will be summarized in this
      article. Given the clear evidence for protective ventilation and bearing in mind
      that clinical application of this easy concept is still not widespread we will
      focus on this aspect.

PMID- 17455140
TI  - [Preoperative functional diagnostics for lung-resecting interventions].
AB  - Preoperative risk stratification for lung surgery requires the determination of
      FEV1 and TLCO. Calculation of relative values and predective postoperative values
      in dependence on the extent of resection is preferable in comparison to absolute
      values. National and international guidelines have different recommendations for
      preoperative functional assessment. In general they recommend cardiopulmonary
      exercise testing if preoperative FEV1 and TLCO are < 80%-pred. or if ppo values
      are < 40%-pred. Inoperability is assumed if ppo values of V'O2-max are < 10
      ml/kg/min or < 35%-pred. On this basis, a more simplified algorithm for the
      preoperative assessment of candidates for lung resection (Hemer algorithm) is
      presented. Nevertheless, there still remain some unresolved questions. These
      concern the assessment of the individual operative risk of patients who are at or
      just beyond the limits of functional operability. Furthermore, there is the fact
      that patients - in spite of a severe functional impairment - are willing to
      accept a higher risk of morbidity and mortality, especially if there is a
      curative option.

PMID- 17455141
TI  - [Successful individualized and targeted therapy of an NSCLC patient with
      Gefitinib based on a predictive assessment of the EGF-receptor mutation status].
AB  - BACKGROUND: Molecular alterations in the tyrosine kinase (TK) domain of the human
      epidermal growth factor receptor (EGFR) have been correlated with tumour
      remission upon treatment with the TK inhibitor Gefitinib in non-small cell lung
      cancer (NSCLC). We have retrospectively investigated the correlation of point
      mutations with clinical response and, based on our retrospective results, used
      predictive molecular assessment as the basis for treatment in one patient.
      METHODS: Mutational analysis was performed in 11 NSCLC-patients (10 responders, 1
      non-responder) among 62 patients treated with Gefitinib within an expanded access
      program. RESULTS: Activating molecular alterations were found in 8/11
      investigated samples (point mutations in exons 18 and 21, deletions in exon 19).
      All molecular changes were found in adenocarcinoma or bronchioloalveolar
      carcinoma. The tumours of two male responders with squamous cell carcinoma showed
      either a wild-type sequence or carried a nonsense mutation. In one patient
      treatment with Gefitinib after prospective assessment of mutations resulted in
      tumour remission and thus proved to be predictive. CONCLUSIONS: Mutations in the
      EGFR TK domain correlate with the clinical response to Gefitinib. The predictive
      assessment of molecular alterations may thus be helpful for treatment decisions
      in selected cases. A clinical response to Gefitinib is nevertheless also found in
      patients with wild-type EGFR.

PMID- 17455142
TI  - [Antismoking campaign].

PMID- 17455144
TI  - Expression of AGR2 in non small cell lung cancer.
AB  - We aimed to evaluate immunohistochemically the expression of the human Anterior
      Gradient-2 (AGR2), a gene which has recently been proposed as an oncogene for
      lung carcinoma development, in non small cell lung cancer and to correlate the
      findings to clinico-pathological data including patient survival. 95 cases of
      NSCLC were immunostained using a polyclonal AGR2 antibody and statistical
      analyses were applied to test for prognostic and diagnostic associations. AGR2
      was expressed in 66.3% of cases, preferentially adenocarcinomas. There were no
      relevant associations with clinico-pathological parameters. A prognostic value of
      AGR2 could not be demonstrated neither in multivariate nor in univariate
      analyses. Interestingly, this is the first study to demonstrate AGR2 expression
      in squamous cell carcinomas. Although a prognostic value of AGR2 seems unlikely
      further studies are warranted to investigate the biological role of AGR2 in NSCLC
      and its differential expression according to histology.

PMID- 17455145
TI  - Immunohistochemical localization of hormones and peptides in the human pituitary
      cells in a case of hypercortisolism by ACTH secreting microadenoma.
AB  - This study assesses the action of hypercortisolism on the hormone and peptide
      periadenoma region of removed ACTH-producing microadenoma. Our findings show that
      cortisol excess affects both ACTH and GH production, with no immunoreaction for
      these hormones. The remaining pituitary hormones (TSH, FSH and PRL) and POMC
      derived peptides (betaEnd, alphaMSH and betaMSH) were not modified. Likewise, we
      observed pituitary immunoreactive cells for Neurotensin (NT), Intestinal
      vasoactive peptide (VIP), Substance P (SP) and Angiotensin-II (Ang-II). The
      colocalization demonstrated that NT was expressed in thyrotrope and gonadotrope
      cells, VIP in gonadotrope cells and SP in corticotrope cells. The results about
      Ang-II were inconclusive. On the other hand, immunoreaction for the NPY and Gal
      peptides were not present. In the adenomatous cells, the peptide NT is present in
      ACTH cells as well as SP. These results suggest a peptide regulation of pituitary
      cells in the pathological state that can differ between normal and tumoural cells
      of the same pituitary.

PMID- 17455146
TI  - Immunolocalization of metallothioneins in different tissues of turbot
      (Scophthalmus maximus) exposed to Cd.
AB  - Metallothioneins (MT) were localized by immunochemistry in different organs and
      cell compartments of turbot exposed to sublethal concentrations (100 ppb) of Cd
      for 7 days. The polyclonal rabbit anti-cod MT antibody (NIVA, Norway) applied
      herein exhibited positive cross-reactivity with turbot MTs. Immunoreactive MTs
      were localized in the branchial epithelium, in the liver and in the kidney of
      turbot. In Cd exposed fishes MTs were demonstrated mainly in branchial chloride
      cells (CC) and to a lesser extend in the area where progenitor cells are located
      and in the cells of the respiratory epithelium (secondary lamellae). A higher
      staining intensity for MTs was observed in CC of the interlamellar space of the
      main branchial epithelium in comparison with control CC. MT-staining was also
      observed in the chondroblasts of the cartilage and in the erythrocytes within
      blood vessels both in control and Cd-exposed specimens. MT immunoreaction was
      high in the liver hepatocytes and weak in the epithelium of the proximal portion
      of the kidney in exposed turbot. The tegument, spleen and muscle were devoid of
      any immunolabelling in both treatments. Ultrastructural studies at the
      transmission electron microscope revealed that Cd-induced MTs were mainly located
      in the cytoplasm of gill CC, the lysosomes and the cytoplasm of hepatocytes and
      in the basal labyrinth of kidney proximal nephrocytes. The differential
      localization/induction of MTs in different cell types described hereby suggests
      that the quantification of the specific expression of MT may be used in
      biomonitoring programs as a biomarker of Cd exposure in aquatic environments.

PMID- 17455147
TI  - Identification of differentially expressed genes in fetal rat forebrain exposed
      to a teratogen by cDNA microarray analysis.
AB  - In an attempt to understand the molecular basis underlying the neural tube
      defects induced by the teratogen, cyclophosphamide (CP), cDNA microarray analysis
      was carried out in neural tubes of embryos derived from normal and CP-treated
      rats. Genes found to have altered expression levels in CP-treated group were
      clustered into groups on the basis of their biological functions. The expression
      profile of different genes involved in transcription of molecules related to cell
      adhesion, inflammation, metabolism and neurotrophic factors pathways as well as
      in still undefined processes was differentially affected by the teratogen
      treatment. The most remarkable change was the up-regulation of genes related to
      an inflammatory process dominated by the fetal brain macrophages viz. amoeboid
      microglia. Amoeboid microglia/brain macrophage expansion, based on gene
      expression and histological analysis, was found to be vigorous at the
      subventricular region. The present results suggest that a vigorous inflammatory
      response involving amoeboid microglia/brain macrophages primarily is an important
      component in CP-induced prenatal development disorder.

PMID- 17455148
TI  - Expression of TFF3 during multistep colon carcinogenesis.
AB  - The pathogenesis of colon cancer is not well understood. This common type of
      cancer is generally believed to occur in a multistep process which involves
      alterations of various tumor suppressor genes and oncogenes during the
      progression through benign lesions towards carcinoma. TFF3 is a product of the
      colonic epithelium and has been implicated in colonic mucosal protection and also
      in the aggressiveness of colon cancer cells. The aim of this study was to analyze
      the expression of TFF3 during propagation towards cancer development in the human
      colon. Colonic tissues representing colitis, adenomatous polyposis, tubulovillous
      adenoma, and mucoid/adeno-carcinomas were processed for immunohistochemistry
      using an antibody specific for human TFF3. The results were correlated with those
      of PCNA-labeling, quantified, and compared with those of control tissues obtained
      from the safe margin of macroscopically normal colonic mucosa of patients with
      colon cancer. The data showed marked down-regulation of TFF3 expression in
      adenomatous polyposis, then TFF3 expression returns to about control level during
      adenoma and remains high during mucoid- and adeno-carcinomas. Colonic tissues
      with highly invasive cancer cells were characterized by statistically significant
      down-regulation of TFF3 expression. The changes observed in expression of TFF3
      showed an inverse correlation with cell proliferation and suggest that it might
      play a protective role against colon carcinogenesis.

PMID- 17455149
TI  - Larval organogenesis of Pagrus pagrus L., 1758 with special attention to the
      digestive system development.
AB  - Organogenesis of the red porgy (Pagrus pagrus L., 1758) was examined from
      hatching until 63 days post-hatching (dph) using histological and histochemical
      techniques. At hatching, the heart appeared as a tubular structure which
      progressively developed into four differentiated regions at 2 dph: bulbus
      arteriosus, atrium, ventricle and sinus venosus. First ventricle and atrium
      trabeculae were appreciated at 6 and 26 dph, respectively. Primordial gill arches
      were evident at 2 dph. Primordial filaments and first lamellae were observed at 6
      and 15 dph, respectively. At mouth opening (3dph), larvae exhausted their yolk
      sac reserves. The pancreatic zymogen granules appeared at 6 dph. Glycogen
      granules, proteins and neutral lipids (vacuoles in paraffin sections) were
      detected in the cytoplasm of the hepatocytes from 4-6 dph. Hepatic sinusoids
      could be observed from 9 dph. Pharyngeal and buccal teeth were observed at 9 and
      15 dph, respectively. Oesophageal goblet cells appeared around 6 dph, containing
      neutral and acid mucosubstances. An incipient stomach could be distinguished at 2
      dph. The first signs of gastric gland development were detected at 26 dph,
      increasing in number and size by 35-40 dph. Gastric glands were concentrated in
      the cardiac stomach region and presented a high content of protein rich in
      tyrosine, arginine and tryptophan. The intestinal mucous cells appeared at 15 dph
      and contained neutral and acid glycoconjugates, the carboxylated mucins being
      more abundant than the sulphated ones. Acidophilic supranuclear inclusions in the
      intestinal cells of the posterior intestine, related to pynocitosis of proteins,
      were observed at 4-6 dph.

PMID- 17455151
TI  - Absence of relevant effects of 5 mT static magnetic field on morphology,
      orientation and growth of a rat Schwann cell line in culture.
AB  - The aim of this study is to observe possible changes in the morphology,
      orientation or cell growth of an in vitro cultured Schwann cell line by 24 h
      exposure to 5 mT static magnetic fields. The magnetic field generator basically
      consists of a pair of circular coils in a Helmholtz arrangement and enables
      temperature to be controlled (37+/-0.1 degrees C). We did not find any
      statistically significant differences in the cell growth rate between control and
      exposed cells, nor did we observe any differences in cell morphology or
      orientation.

PMID- 17455150
TI  - Controversial relationship between the expression of the RB pathway components
      and RB protein phosphorylation in human breast cancer.
AB  - Recent data challenge the relevance of the RB pathway to cancer based on RB
      inactivation, at least in breast tumors. To obtain information on the actual role
      of the components of the RB pathway in tumor progression we decided to
      investigate whether their quantitative changes were associated with variations in
      the level of RB phosphorylation in human breast cancer. A series of 68 human
      primary breast carcinomas was studied. Five cases were excluded from the study
      due to their lack of RB expression. In the remaining 63 cases the expression of
      cyclin D1, cdk4, cyclin E, and INK4a mRNA was assessed by real-time RT-PCR. The
      level of RB phosphorylated protein (ppRB) and p27 expression was
      immunohistochemically analyzed by measuring the percentage of stained cells
      (labeling index, LI). Cell proliferation rate was measured by Ki67 LI evaluation.
      The ppRB LI ranged from 5.2 to 73.8 and, as expected, was strongly related to the
      Ki67 LI (r=0.80; p<0.001). The expression of cyclin D1 mRNA, expressed in
      arbitrary units (a. u.), ranged from 1.15 to 123.0 and was inversely related to
      the ppRB LI (p=0.021) and Ki67 LI (p<0.001). Neither the cdk4 (range from 0.07 to
      1.13 a. u.) nor the cyclin E (range from 0.13 to 9.27 a. u.) mRNA expression was
      significantly associated with the ppRB LI (p=0.962 and p=0.103, respectively).
      Cyclin E was related to Ki67 LI (p=0.022). Both INK4a mRNA (range from 0.01 to
      0.60 a. u.) and p27 (LI from 0.0 to 73.1) values were inversely related to the
      ppRB LI (p=0.022 and p=0.014, respectively). Cyclin D1, cdk4, and cyclin E mRNA
      expressions were not significantly related to one another. In human primary
      breast cancers, the expression levels of the factors known to facilitate the cell
      cycle progression by RB protein phosphorylation were not positively related to
      ppRB-LI. Pathological increases of cyclin D, cdk4, and cyclin E are very likely
      associated with other biological functions other than their well-established
      action on cell cycle progression.

PMID- 17455152
TI  - Impact of the complement cascade on posttraumatic cartilage inflammation and
      degradation.
AB  - The limited ability of articular cartilage to recover from injury, remains an
      unsolved clinical challenge in orthopaedic surgery. Persistent injury of the
      articular surface can lead to the development of posttraumatic osteoarthritis.
      The local inflammatory response contributes to the pathogenesis of osteoarthritis
      by inducing chondrocyte apoptosis and the de-regulation of chondrocyte matrix
      remodelling. The role of the complement system in contributing to secondary
      inflammation-mediated cartilage degradation represents a newer field of
      investigation. The purpose of this review article is to summarize the known
      complement-mediated actions in cartilage homeostasis and injury. This article
      focuses on the known effects of complement on secondary chondrocyte apoptosis,
      and the interplay of the complement system with pro-inflammatory cytokines.
      Pharmacological therapies related to complement inhibition will be discussed as
      they potentially represent a new avenue for attenuating the effect of the
      complement system on cartilage repair.

PMID- 17455153
TI  - The role of hepcidin and ferroportin in iron absorption.
AB  - The field of iron metabolism is moving rapidly. There have been significant
      advances in our understanding of how proteins carry out the process of iron
      absorption. The three main tissues involved in iron exchange are the enterocyte
      which contributes new iron to the system, the hepatocyte which stores and
      releases iron and the macrophages which recycles iron from effete red blood cells
      to the plasma. This review examines recent evidence into the function of the iron
      transporters divalent metal transporter and ferroportin in enterocytes. Evidence
      is also provided from the author's laboratory which presents an alternative
      hypothesis into how hepcidin a key regulator molecule might interact with
      ferroportin in enterocytes. It is proposed that ferroportin operates differently
      in enterocytes compared with macrophages. Specifically in enterocytes ferroportin
      appears to function in the uptake stage of iron absorption.

PMID- 17455154
TI  - Mechanisms of skeletal muscle degradation and its therapy in cancer cachexia.
AB  - Severe or chronic disease can lead to cachexia which involves weight loss and
      muscle wasting. Cancer cachexia contributes significantly to disease morbidity
      and mortality. Multiple studies have shown that the metabolic changes that occur
      with cancer cachexia are unique compared to that of starvation. Specifically,
      cancer patients seem to lose a larger proportion of skeletal muscle mass. There
      are three pathways that contribute to muscle protein degradation: the lysosomal
      system, cytosolic proteases and the ubiquitin (Ub)-proteasome pathway. The Ub
      proteasome pathway seems to account for the majority of skeletal muscle
      degradation in cancer cachexia and is stimulated by several cytokines including
      tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interferon-gamma
      and proteolysis-inducing factor. Cachexia is particularly severe in pancreatic
      cancer and contributes significantly to the quality of life and mortality of
      these patients. Several factors contribute to weight loss in these patients,
      including alimentary obstruction, pain, depression, side effects of therapy and a
      high catabolic state. Although no single agent has proven to halt cachexia in
      these patients there has been some progress in the areas of nutrition with
      supplementation and pharmacological agents such as megesterol acetate, steroids
      and experimental trials targeting cytokines that stimulate the Ub-proteasome
      pathway.

PMID- 17455155
TI  - Endothelial heat shock response in cerebral ischemia.
AB  - Blood vessels and nerve fibers often course alongside one another in an orderly
      fashion throughout the brain. This clustering gives rise to a reciprocal
      signaling network between endothelial and nerve cells that follows highly
      stereotyped anatomical patterns. One such molecular signal that is produced by
      endothelial cells and acts on surrounding neurons is heat shock protein 70. Here
      we briefly review recent studies that have revealed a critical role of this
      signaling pathway during harmful insults to the brain, particularly during
      episodes of cerebral ischemia.

PMID- 17455156
TI  - [Outcomes of surgical treatment in 100 patients with arteriovenous malformations
      of the brain].
AB  - AIM: To conduct a descriptive analysis of a series of patients with arteriovenous
      malformations (AVM) that had been treated surgically. PATIENTS AND METHODS: Of a
      total of 189 adult patients with AVM evaluated consecutively in our hospital, 100
      patients who had undergone surgical treatment were selected; a number of
      demographic, clinical and radiological aspects were then analysed, together with
      data concerning any associated vascular lesions, the type of surgical treatment,
      angiographic results and clinical outcomes. RESULTS: The mean age was 34 years
      (range: 15-71 years). The most common presenting symptom was intracranial
      haemorrhage, which occurred in 60 cases (60%). The AVM were located in the
      supratentorial convexity in 79% of cases, 8% were deep and 13% were situated in
      the cerebellum. The most frequent degree, according to the Spetzler and Martin
      scale, was grade III. Seventeen patients had other associated lesions and it
      should be noted that eight patients had aneurysms. Most of the patients (78%)
      underwent elective surgery and, in two cases, post-embolisation. Surgical
      treatment (salvage surgery) was performed in 13 patients (13%) when other
      therapeutic options failed and seven patients were submitted to emergency
      operations because of brain haemorrhages. The postoperative angiographic study
      showed complete removal of the AVM in 98% of cases. The clinical outcomes were as
      follows: 75%, good recovery; 20%, moderate incapacity; and 5%, an important
      degree of incapacity. CONCLUSION: Surgery is the best therapeutic option for
      patients with AVM, if they are selected in an appropriate manner.

PMID- 17455157
TI  - [The neuropsychological profile of mild cognitive impairment with involvement of
      multiple cognitive areas. The importance of amnesia in distinguishing two
      subtypes of patients].
AB  - INTRODUCTION: The use of diagnostic criteria for mild cognitive impairment (MCI)
      that do not require the presence of amnesia enables patients to be classified
      into three types of MCI: pure amnestic MCI (aMCI), MCI with involvement of
      multiple cognitive functions and amnesia (mf-aMCI) and MCI with involvement of
      multiple cognitive functions without amnesia, or non-amnestic MCI (mf-nonaMCI).
      AIM: To determine whether patients with MCI with involvement of multiple
      functions (mfMCI) have a different profile of cognitive involvement depending on
      whether amnesia is present or not. PATIENTS AND METHODS: Out of a total sample of
      175 patients with MCI, we studied 138 with mfMCI. Of these, 109 (79%) had memory
      disorders (mf-aMCI) and 29 (21%) did not (mf-nonaMCI). For each group of
      patients, we determined the percentage who scored below normal in each of the
      items on the abbreviated Barcelona test. RESULTS: Patients with mf-aMCI failed
      more frequently in temporal orientation, naming and semantic category evocation
      tests. Patients with mf-nonaMCI failed more often in motor praxis and abstraction
      tests. Differences were statistically significant. Additionally, it was noted
      that patients with mf-nonaMCI tended to make more mistakes in attention tests.
      CONCLUSIONS: The presence of amnesia allows us to identify an mf-aMCI group with
      a cognitive profile suggesting temporal involvement, unlike the mf-nonaMCI group,
      whose members have a cognitive profile that suggests subcortical compromise.

PMID- 17455158
TI  - [The prevalence of cerebrovascular disease in the rural community of Salama,
      Honduras, using the capture-recapture epidemiological method].
AB  - INTRODUCTION: Cerebrovascular disease (CVD) is one of the leading causes of
      mortality and disability in Honduras. In 2001 the first epidemiological study
      conducted into stroke or CVD in the urban district of Colonia Kennedy in
      Tegucigalpa, Honduras, was published; the prevalence rate was found to be 5.7 x
      1000 inhabitants. To date few epidemiological studies have been carried out on
      CVD in rural areas of Central America. AIM: To determine the prevalence of CVD in
      the rural community of Salama, Olancho, Honduras, using the epidemiological
      method known as capture-recapture. SUBJECTS AND METHODS: The capture-recapture
      technique includes three sources of data: door-to-door interviews, research of
      medical records and interviews held with community leaders. All the residents in
      the rural community of Salama, Olancho, in north-western Honduras, were evaluated
      and the prevalence day was 5th May, 2005. The World Health Organisation's
      definition of CVD and the recommendations of the 'Global stroke initiative' were
      used. RESULTS: A total of 1121 households were visited, which involved a total
      population of 5608 inhabitants. The prevalence for CVD was found to be 3.6 x 1000
      inhabitants. CONCLUSIONS: The prevalence rate for CVD in the rural community of
      Salama, Honduras, is similar to that reported for other rural regions of Latin
      America. The capture-recapture technique is recommended for conducting studies
      into the prevalence of stroke in rural areas.

PMID- 17455159
TI  - [Mismatch negativity and conscience level in severe traumatic brain injury].
AB  - INTRODUCTION: The mismatch negativity (MMN) is a component of the long-latency
      auditory evoked potentials, that are used to check the functionality of automatic
      attentional processes of attentive information processing. Vegetative state
      diagnosis is frequent following severe traumatic brain injury (TBI). Eventually,
      some patients improve their condition to another one called minimal conscientious
      state. AIM: To evaluate the diagnostic usefulness of MMN in severe TBI patients
      during the subacute phase after leaving the neurological intensive care unit.
      PATIENTS AND METHODS: We gathered MMN results from 19 patients (12 males and 7
      females; 8 vegetative state and 11 minimal conscientious state) with ages between
      17 and 59 years (mean: 27.3 years). The delay between TBI onset and MMN
      recordings were greater than 2 months (mean: 181 days). During the recording
      session, patients were evaluated by means of the Multisociety Task Force on
      Persistent Vegetative State scale. RESULTS: All the minimal conscientious state
      patients (100%) showed MMN potential. In seven of the vegetative state patients
      (87.5%) the MMN was not found. The remaining MMN potential positive vegetative
      state patient improved to MCS 16 days after testing. CONCLUSIONS: MMN is a valid
      tool for differentiating vegetative state from MCS during the subacute phase of
      severe TBI. Hence it is a useful aid to the clinical evaluation. This would
      diminish the impact of a possible diagnostic error and its prognosis on
      therapeutical management, family and health costs. It can also be used for
      evaluating other brain disorders with altered consciousness.

PMID- 17455160
TI  - [Description of a novel test for the early detection of Alzheimer's disease].
AB  - INTRODUCTION: Diagnosing Alzheimer's disease (AD) as soon as possible is critical
      to achieve an effective treatment of patients. AIM: To make up a test capable of
      differentiating those patients suffering from the early stages of AD compared to
      healthy people or patients with mild cognitive impairment (MCI). SUBJECTS AND
      METHODS: A test with 10 memory and language tasks was applied to 85 people: 34 in
      the early stage of probable AD, 26 with MCI, and 25 healthy people. The groups
      did not differ with regard to age, sex or studies. RESULTS: The analysis of
      variance showed significative differences between groups in all tasks as well as
      in the global score. Sensibility and specificity were calculated to MCI and AD.
      CONCLUSIONS: We designed a new test to detect AD patients on an early stage that
      is quick and easy to apply. The preliminary scale results in controls, MCI and
      early AD are shown.

PMID- 17455161
TI  - [Reversible posterior leukoencephalopathy syndrome: an infrequent complication in
      the course of haemolytic-uremic syndrome].
AB  - INTRODUCTION: Posterior reversible leukoencephalopathy syndrome (PRLS) is
      characterised by the sudden and usually transient onset of headaches, visual
      disorders, decreased awareness and convulsions associated with cerebral oedema in
      the posterior areas of the brain. Different reports have associated it with
      numerous processes and possibly with haemolytic-uremic syndrome (HUS). We
      describe a new case of PRLS within the context of HUS. CASE REPORT: We describe
      the case of a 4-year-old child with HUS who developed arterial hypertension that
      did not respond well to treatment and kidney failure that required renal
      replacement therapy. During the course of the disease the patient presented
      several transient episodes of headache, a lowered level of consciousness and
      seizures. Magnetic resonance imaging revealed multiple lesions in the white
      matter and the cortex that were hyperintense in T2 and hypointense in T1 situated
      in the bilateral occipital and right frontotemporoparietal regions. The patient
      made a full clinical recovery in a few days, although an magnetic resonance
      imaging scan performed at six weeks after the last episode showed partial
      remission of the lesions and a small cerebral infarction. CONCLUSIONS: The
      pathogenesis of PRLS is still not fully understood. Its multifactorial origin
      suggests that several different mechanisms may be involved. In the case reported
      here, it is possible that the arterial hypertension, retention of fluids and even
      the sessions of dialysis played a role in its development.

PMID- 17455162
TI  - [What is theory of mind?].
AB  - INTRODUCTION: The brain is, basically speaking, a predictive machine, designed to
      reduce environmental incertitude. The theory of mind originated from a concept
      found in the pioneer works of Premack and Woodruf and refers to the ability to
      understand and predict the behaviour of other people, their knowledge,
      intentions, emotions and beliefs. This term was initially confined to the study
      of primatology and aetiology of autism, proposing that the cause of generalised
      disorders in development was an absence of theory of mind. In recent years
      however we have observed a great proliferation of studies on this complex concept
      and its affectation in various pathologies. DEVELOPMENT: This work proposes
      dividing the concept of theory of mind into different processes and how to
      evaluate each one. It furthermore aims at establishing the brain structures
      related with each level of theory of mind. These levels of complexity are: facial
      recognition of emotions, first and second order beliefs, social usage of
      language, social behaviour and empathy. CONCLUSIONS: To conclude, we reflect on
      certain relevant theoretic concepts on the matter such as the role of prefrontal
      cortex in the theory of mind, the categorical versus dimensional when we refer to
      this type of concept; modularity or neural systems, emotional and social
      intelligence versus cognitive intelligence or the role of bi-directionality in
      these complex cognitive processes.

PMID- 17455164
TI  - [Recommendations for optimising the treatment of multiple sclerosis in Latin
      America].
AB  - INTRODUCTION: Multiple sclerosis (MS) is the most common primary demyelinating
      disease affecting the central nervous system. In recent years the development of
      new drugs that have been shown to modify the natural history of MS have had a
      substantial impact on the treatment of the disease. AIMS: To harmonise and
      integrate the evidence available on optimising the treatment of patients with MS.
      DEVELOPMENT: In order to fulfil our main aim, a group of experts from different
      Latin American countries drew up a list of statements related to the use of
      immunomodulatory agents in the different clinical forms of the disease and the
      strategies that should be considered in cases in which the therapeutic response
      was suboptimal. Each of the participants used a structured scale to express the
      extent to which he or she agreed or disagreed, and a consensus was considered to
      have been reached when acceptance of each of the statements was equal to or
      higher than 80%. CONCLUSIONS: These recommendations will provide neurologists
      with the tools needed to make decisions that optimise the treatment of MS
      patients.

PMID- 17455163
TI  - [Migraine and vertigo].
AB  - INTRODUCTION: Headache and dizziness are two of the most frequent symptoms that
      lead patients to visit neurology outpatient services. One of the most interesting
      associations is the one existing between migraine and vertigo. Different terms
      have been used in the literature to refer to this clinical picture, but perhaps
      the one that best defines this relation is that of recurring migraine-associated
      vertigo, which should be considered an entity in its own right. DEVELOPMENT:
      Migraine and vertigo are two clinical features that tend to occur together,
      possibly as a result of their pathophysiology; we must be capable of recognising
      the type of neuro-otological disorder our patient has in order to be able to aim
      the diagnostic tests in the right direction and to carry out a satisfactory
      treatment. CONCLUSION: New diagnostic criteria are proposed for recurring
      migraine-associated vertigo.

PMID- 17455165
TI  - [Post-encephalitic syndromes in the Spanish medical literature].
AB  - AIM: A large number of patients with encephalitis lethargica developed different
      post-encephalitic syndromes (PES), which have an important medical and social
      impact. We studied the clinical and historical aspects of PES in Spain by
      reviewing the medical literature published in this country between 1918 and 1936.
      DEVELOPMENT: There are no statistical data concerning PES in Spain, although
      Spanish physicians drew attention to their high rate of prevalence and their
      repercussions on community health. Most of the 140 patients that were reviewed
      (74%) presented predominant Parkinsonism, but some features of Parkinsonism were
      observed in nearly all cases. Other movement disorders (focal dystonias, chorea,
      myoclonus, oculogyric crises, abnormalities affecting breathing rate) were
      described, as well as sleep, endocrine and vegetative disorders. Psychiatric
      disorders were often reported, the most frequent being bradyphrenia associated to
      Parkinsonism, but a hypomanic picture with impulsive behaviour was very
      characteristic among young people. PES was diagnosed on average two years after
      the episode of acute encephalitis lethargica, although it often appeared
      immediately afterwards. Many studies discuss the contribution made by PES to
      further our knowledge of the pathophysiology of extrapyramidal diseases and about
      the involvement of the basal ganglia in psychiatric and behavioural disorders.
      CONCLUSIONS: Despite the absence of statistical data, Spanish authors highlighted
      the important repercussions the PES had on community health, as well as the role
      they played in extending our knowledge of the pathophysiology of the basal
      ganglia. Cases of Parkinsonism were predominant, although all kinds of post
      encephalitic manifestations were reported.

PMID- 17455167
TI  - [Posterior fossa empyema as a complication deriving from thrombophlebitis of the
      cavernous sinus caused by Enterococcus faecium].

PMID- 17455166
TI  - [Gait over ground and underwater in children with myelomeningocele].

PMID- 17455168
TI  - [Intraarterial thrombolysis in ischaemic stroke as a complication of heart
      surgery].

PMID- 17455169
TI  - Pulmonary dysfunction and impaired granulocyte homeostasis result in poor
      survival of Jam-C-deficient mice.
AB  - Jam-C(-/-) mice exhibit growth retardation and multilobular pneumonia concomitant
      with poor survival of the mice under conventional housing conditions. The
      deficient mice present a mega-oesophagus and have altered airway responsiveness.
      In addition, the number of circulating granulocytes is increased in Jam-C(-/-)
      mice as compared to control animals. These phenotypes probably reflect the
      different functions of JAM-C expressed by endothelial and mesenchymal cells.
      Indeed, the deregulation in the number of circulating granulocytes is caused by
      the lack of JAM-C expression on endothelial cells since rescuing endothelial
      expression of the protein in the Jam-C(-/-) mice is sufficient to restore
      homeostasis. More importantly, the rescue of vascular JAM-C expression is
      accompanied by better survival of deficient mice, suggesting that endothelial
      expression of JAM-C is mandatory for animal survival from opportunistic
      infections and fatal pneumonia.

PMID- 17455171
TI  - Generation, characterization, and electrochemical behavior of the palladium
      hydride cluster [Pd3(dppm)3(mu3-CO)(mu3-H)]+ (dppm=Bis(diphenylphosphinomethane).
AB  - Addition of formate on the dicationic cluster [Pd(3)(dppm)(3)(mu(3)-CO)](2+)
      (dppm=bis(diphenylphosphinomethane) affords quantitatively the hydride cluster
      [Pd(3)(dppm)(3)(mu(3)-CO)(mu(3)-H)](+). This new palladium-hydride cluster has
      been characterised by (1)H NMR, (31)P NMR and UV/Vis spectroscopy and MALDI-TOF
      mass spectrometry. The unambiguous identification of the capping hydride was made
      from (2)H NMR spectroscopy by using DCO(2) (-) as starting material. The
      mechanism of the hydride complex formation was investigated by UV/Vis stopped
      flow methods. The kinetic data are consistent with a two-step process involving:
      1) host-guest interactions between HCO(2) (-) and [Pd(3)(dppm)(3)(mu(3)-CO)](2+)
      and 2) a reductive elimination of CO(2). Two alternatives routes to the hydride
      complex were also examined : 1) hydride transfer from NaBH(4) to
      [Pd(3)(dppm)(3)(mu(3)-CO)](2+) and 2) electrochemical reduction of
      [Pd(3)(dppm)(3)(mu(3)-CO)](2+) to [Pd(3)(dppm)(3)(mu(3)-CO)](0) followed by an
      addition of one equivalent of H(+). Based on cyclic voltammetry, evidence for a
      dual mechanism (ECE and EEC; E=electrochemical (one-electron transfer),
      C=chemical (hydride dissociation)) for the two-electron reduction of
      [Pd(3)(dppm)(3)(mu(3)-CO)(mu(3)-H)](+) to [Pd(3)(dppm)(3)(mu(3)-CO)](0) is
      provided, corroborated by digital simulation of the experimental results.
      Geometry optimisations of the [Pd(3)(H(2)PCH(2)PH(2))(3)(mu(3)-CO)(mu(3)-H)](n)
      model clusters were performed by using DFT at the B3 LYP level. Upon one-electron
      reductions, the Pd--Pd distance increases from a formal single bond (n=+1), to
      partially bonding (n=0), to weak metal-metal interactions (n=-1), while the Pd--H
      bond length remains relatively the same.

PMID- 17455170
TI  - The secretory leukocyte protease inhibitor (SLPI) suppresses cancer cell invasion
      but promotes blood-borne metastasis via an invasion-independent pathway.
AB  - An invasion-independent pathway has been proposed as a novel mechanism in blood
      borne metastasis, where tumour cells enveloped by sinusoidal tumour vessels enter
      the circulation without vascular invasion. We previously identified the secretory
      leukocyte protease inhibitor (SLPI) as a candidate gene responsible for this
      pathway. In this study, the functional role of SLPI in metastatic dissemination
      was investigated. We transfected the SLPI gene into a poorly metastatic clone of
      the MCH66 mouse mammary tumour cell line. Over-expression of SLPI promoted in
      vivo growth and spontaneous metastasis to the lung, whereas it suppressed
      invasive activity in vitro. The inoculated tumours of SLPI-transfectants
      exclusively induced a sinusoidal vasculature and subsequently produced
      endothelial-coated tumour emboli, which are morphological indices of the invasion
      independent pathway. In addition, exogenous SLPI inhibited the migration activity
      through Matrigel of both tumour cells and human umbilical vein endothelial cells
      (HUVECs). In vivo angiogenesis assays also demonstrated that SLPI suppressed the
      migration of newly formed blood vessels. These results suggest that an anti
      migratory effect of SLPI on tumour-associated endothelial cells may induce
      vascular remodelling to form a sinusoidal architecture, and consequently promote
      invasion-independent metastasis. This study provides a new model for metastasis,
      based on the mechanism regulated by anti-invasive factors, such as SLPI.

PMID- 17455173
TI  - Impact of bridging units on the dynamics of photoinduced charge generation and
      charge recombination in donor-acceptor dyads.
AB  - We estimate, at a full quantum-chemical level, the various molecular parameters
      governing the rate of photoinduced charge generation and charge recombination in
      model organic structures containing a donor and an acceptor unit in view of the
      possible use of such systems in organic solar cells. The rate of through-space
      excitation dissociation, as predicted in the framework of the Marcus-Levich
      Jortner theory, is found to be low in comparison to intramolecular decay
      processes when the donor and acceptor molecules are lying in a head-to-tail
      arrangement and high when the donor and acceptor molecules are superimposed in a
      cofacial arrangement. The charge separation rates for side-by-side donor-acceptor
      dyads are significantly increased by promoting through-bond interactions in
      covalently linked donor and acceptor units. This has motivated a detailed
      quantitative analysis of the influence of the nature, size, and conformation of
      the bridging moiety on the calculated transfer rates.

PMID- 17455174
TI  - AxBAx-type block-graft polymers with soft methacrylate middle segments and hard
      styrene outer grafts: synthesis, morphology, and mechanical properties.
AB  - Novel copolymers with controlled architectures can function as new building
      blocks for well-defined nanostructures on the basis of microphase separation,
      unlike conventional ABA triblock copolymers. A series of well-defined A(x)BA(x)
      type block-graft copolymers consisting of soft middle segments (dodecyl
      methacrylate (DMA)) and hard outer graft chains (styrene (St)) were synthesized
      by ruthenium-catalyzed living radical block and graft polymerization. NMR
      spectroscopy and size-exclusion chromatography combined with multiangle laser
      light scattering confirmed the well-defined structure of the A(x)BA(x) block
      graft copolymers with backbones and graft chains of controlled lengths.
      Transmission electron microscopy and transmission electron microtomography
      revealed a series of morphologies for the copolymers. Morphological changes were
      observed from PSt "honeycomb" cylinders to lamellae and poly(DMA) cylinders with
      increasing PSt-graft content, whereby the phase diagram was shifted significantly
      to lower volume fractions of the larger-number component (St) relative to those
      of the corresponding ABA triblock copolymers. More specifically, poly(DMA)
      cylinders were observed even before the St content reached 50 wt %. The A(x)BA(x)
      and ABA copolymers with 17-30 wt % of St exhibited characteristics of a
      thermoplastic elastomer with tensile strengths of 1-6 MPa and elongations at
      break of 70-300 %. These mechanical properties can be related well to the
      microphase structures of the A(x)BA(x) and ABA copolymers.

PMID- 17455175
TI  - Metal-ion-mediated tuning of duplex DNA binding by bis(2-(2-pyridyl)-1H
      benzimidazole).
AB  - Studies of double-stranded-DNA binding have been performed with three isomeric
      bis(2-(n-pyridyl)-1H-benzimidazole)s (n=2, 3, 4). Like the well-known Hoechst
      33258, which is a bisbenzimidazole compound, these three isomers bind to the
      minor groove of duplex DNA. DNA binding by the three isomers was investigated in
      the presence of the divalent metal ions Mg(2+), Co(2+), Ni(2+), Cu(2+), and
      Zn(2+). Ligand-DNA interactions were probed with fluorescence and circular
      dichroism spectroscopy. These studies revealed that the binding of the 2-pyridyl
      derivative to DNA is dramatically reduced in the presence of Co(2+), Ni(2+), and
      Cu(2+) ions and is abolished completely at a ligand/metal-cation ratio of 1:1.
      Control experiments done with the isomeric 3- and 4-pyridyl derivatives showed
      that their binding to DNA is unaffected by the aforementioned transition-metal
      ions. The ability of 2-(2-pyridyl)benzimidazole to chelate metal ions and the
      conformational changes of the ligand associated with ion chelation probably led
      to such unusual binding results for the ortho isomer. The addition of
      ethylenediaminetetraacetic acid (EDTA) reversed the effects completely.

PMID- 17455176
TI  - Molecular basis for trehalase inhibition revealed by the structure of trehalase
      in complex with potent inhibitors.

PMID- 17455177
TI  - Discovering and verifying elusive fullerene cage isomers: structures of C2-p11
      (C74-D3h)(CF3)12 and C2-p11-(C(78)-D3h5)(CF3)12.

PMID- 17455178
TI  - A sesquineolignan with a spirodienone structure from Pinus sylvestris L.

PMID- 17455179
TI  - From polynorbornene to the complementary polynorbornene by replication.

PMID- 17455180
TI  - Para-hydrogen-enhanced hyperpolarized gas-phase magnetic resonance imaging.

PMID- 17455181
TI  - Are psychotropics drugs used in pregnancy?
AB  - PURPOSE: To assess the prevalence and characteristics of psychiatric drug use in
      pregnancy. METHODS: A prospective observational study was performed on a total of
      1332 consecutive women admitted for delivery, during a 3 months period, in the
      public obstetric services of Tenerife Island (covering a population of 1 000 000
      inhabitants). RESULTS: Less than 4% (3.6%) of the women recognised having a
      psychiatric disorder, and only 2.5% were receiving psychiatric drug treatment at
      the moment they knew they were pregnant; of those, 68.7% introduced substantial
      modifications in their treatment at that moment, 47.9% did not report any change
      with respect to the period before pregnancy and 35.4% recognised that their mood
      was worse than previously. Although patients affected by a psychiatric disorder
      registered a higher rate of abdominal delivery, no differences in delivery or
      obstetric complications were found between women with and without psychiatric
      illness or in relation to psychiatric drug treatment. CONCLUSIONS: Compared to
      the literature, the studied population shows a lower rate of psychiatric problems
      and pharmacological treatment. This might reflect underrecognition or
      undertreatment.

PMID- 17455182
TI  - Influence of different ECM mimetic peptide sequences embedded in a nonfouling
      environment on the specific adhesion of human-skin keratinocytes and fibroblasts
      on deformable substrates.
AB  - Mechanical stress is a decisive factor for the differentiation, proliferation,
      and general behavior of cells. However, the specific signaling of
      mechanotransduction is not fully understood. One basic problem is the clear
      distinction between the different extracellular matrix (ECM) constituents that
      participate in cellular adhesion and their corresponding signaling pathways.
      Here, a system is proposed that enables mechanical stimulation of human-skin
      derived keratinocytes and human dermal fibroblasts that specifically interact
      with peptide sequences immobilized on a non-interacting but deformable substrate.
      The peptide sequences mimic fibronectin, laminin, and collagen type IV, three
      major components of the ECM. To achieve this, PDMS is activated using ammonia
      plasma and coated with star-shaped isocyanate-terminated poly(ethylene glycol)
      based prepolymers, which results in a functional coating that prevents unspecific
      cell adhesion. Specific cell adhesion is achieved by functionalization of the
      layers with the peptide sequences in different combinations. Moreover, a method
      that enables the decoration of deformable substrates with cell-adhesion peptides
      in extremely defined nanostructures is presented. The distance and clustering of
      cell adhesion molecules below 100 nm has been demonstrated to be of utmost
      importance for cell adhesion. Thus we present a new toolbox that allows for the
      detailed analysis of the adhesion of human-skin-derived cells on structurally and
      biochemically decorated deformable substrates.

PMID- 17455183
TI  - Role of the preparation procedure in the formation of spherical and monodisperse
      surfactant/polyelectrolyte complexes.
AB  - Complexes formed by a double-tail cationic surfactant, didodecyldimethyl ammonium
      bromide, and an anionic polyelectrolyte, an alternating copolymer of poly(styrene
      alt-maleic acid) in its sodium salt form, were investigated with respect to
      variation in the charge ratio (x) between the polyelectrolyte negative charges
      and the surfactant positive charges. The morphology and microstructure of the
      complexes were studied by light microscopy and small-angle X-ray scattering for
      different preparation conditions. Independent of the sample preparation procedure
      and the charge ratio x, the X-ray results show that the microscopic structure of
      the complexes is a condensed lamellar phase. By contrast, the morphology of the
      complexes changes dramatically with the preparation procedure. The complexes
      formed by mixing a surfactant solution and a polyelectrolyte solution strongly
      depend on x and are always extremely heterogeneous in size and shape.
      Surprisingly, we show that, when the two solutions interdiffuse slowly, spherical
      complexes of micrometric and rather uniform size are systematically obtained,
      independently on the initial relative amount of surfactant and polyelectrolyte.
      The mechanism for the formation of these peculiar complexes is discussed.

PMID- 17455184
TI  - Aromaticity in metallabenzenes.
AB  - The electronic structure and bonding situation in 21 metallabenzenes (metal=Os,
      Ru, Ir, Rh, Pt, and Pd) were investigated at the DFT level (BP86/TZ2P) by using
      an energy decomposition analysis (EDA) of the interaction energy between various
      fragments. The aim of the work is to estimate the strength of the pi bonding and
      the aromatic character of the metallacyclic compounds. Analysis of the electronic
      structure shows that the metallacyclic moiety has five occupied pi orbitals, two
      with b1 symmetry and three with a2 symmetry, which describe the pi-bonding
      interactions. The metallabenzenes are thus 10 pi-electron systems. This holds for
      16-electron and for 18-electron complexes. The pi bonding in the metallabenzenes
      results mainly from the b1 contribution, but the a2 contribution is not
      negligible. Comparison of the pi-bonding strength in the metallacyclic compounds
      with acylic reference molecules indicates that metallabenzenes should be
      considered as aromatic compounds whose extra stabilization due to aromatic
      conjugation is weaker than in benzene. The calculated aromatic stabilization
      energies (ASEs) are between 8.7 kcal mol(-1) for 13 and 37.6 kcal mol(-1) for 16
      which is nearly as aromatic as benzene (ASE=42.5 kcal mol(-1)). The classical
      metallabenzene model compounds 1 and 4 exhibit intermediate aromaticity with ASE
      values of 33.4 and 17.6 kcal mol(-1). The greater stability of the 5d complexes
      compared with the 4d species appears not to be related to the strength of pi
      conjugation. From the data reported here there is no apparent trend or pattern
      which indicates a correlation between aromatic stabilization and particular
      ligands, metals, coordination numbers or charge. The lower metal-C5H5 binding
      energy of the 4d complexes correlates rather with weaker sigma-orbital
      interactions.

PMID- 17455185
TI  - A bioorganometallic approach for the electrochemical detection of proteins: a
      study on the interaction of ferrocene-peptide conjugates with papain in solution
      and on Au surfaces.
AB  - In this paper, a new bioorganometallic approach for the detection of proteins
      using surface-bound ferrocene-peptide conjugates is presented. Specifically, a
      series of peptide conjugates of 1'-aminoferrocene-1-carboxylic acid (ferrocene
      amino acid, Fca) is synthesized: Boc-Fca-Gly-Gly-Tyr(Bzl)-Arg(NO2)-OMe (2), Thc
      Fca-Gly-Gly-Tyr(Bzl)-Arg(NO2)-OMe (3), Thc-Fca-Gly-Gly-Tyr(Bzl)-Arg(NO2)-OH (4),
      Boc-Fca-Gly-Gly-Arg(Mtr)-Tyr-OMe (7), Thc-Fca-Gly-Gly-Arg(Mtr)-Tyr-OMe (8), Thc
      Fca-Gly-Gly-Arg(Mtr)-Tyr-OH (9), Thc-Fca-Gly-Gly-Arg-Tyr-OH (10). The peptide is
      conjugated to the C-terminal side of Fca and compounds 4, 7-10 possess a thiostic
      acid linked to the N-terminal side of Fca in order to facilitate formation of
      thin films on gold substrates. Competitive inhibition towards papain was
      determined for Thc-Fca-Gly-Gly-Tyr(Bzl)-Arg(NO2)-OH (4), Thc-Fca-Gly-Gly-Arg(Mtr)
      Tyr-OH (9) and Thc-Fca-Gly-Gly-Arg-Tyr-OH (10). The binding interaction between
      the peptide modified substrates and papain enzyme was studied using real-time
      surface plasmon resonance (SPR) imaging. Peptide 10 showed the strongest binding
      affinity to papain. Adsorption/desorption rate constants were ka = 1.75+/-0.05 x
      10(5) M(-1) s(-1) and kd = 2.90 +/- 0.05 x 10(-2) s(-1). Interactions of papain
      with Fca-peptide 10 were investigated by cyclic voltammetry. The interaction
      results were also verified by measuring the electrochemical response of the
      peptide-papain interaction as function of increasing enzyme concentration. A
      linear relationship was observed for papain concentration of up to 80 nM.
      Shifting to higher potentials as well as decrease in the overall signal intensity
      was observed. The detection limit was 4 x 10(-9) M.

PMID- 17455186
TI  - Assembly of infinite silver(I) columns, chains, and bridged aggregates with
      supramolecular synthon bearing substituted phenylethynides.
AB  - Structural correlation in a series of eight silver(I) complexes bearing
      substituted phenylethynide ligands was systematically investigated through
      variation of the position or steric bulk of substituents on the aromatic ring.
      All coordination frameworks are constructed with the supramolecular synthon Ar--C
      triple bond C superset Ag(n) (Ar=4-MeC6H4, 3-MeC6H4, 2-MeC6H4, 4-tBuC6H4, 3,5
      (CF3)2C6H3; n=4, 5), and the presence of coexisting ligands was found to
      influence the supramolecular assembly. The role of pi-pi stacking, C--Hpi and Ag
      C(aromatic) interactions in stabilizing the coordination networks is also
      discussed.

PMID- 17455187
TI  - First synthesis of 2'-deoxyfluoropuromycin analogues: experimental insight into
      the mechanism of the Staudinger reaction.
AB  - The N(6),N(6)-dedimethyl-2'-deoxyfluoro analogue of puromycin (= 3'-deoxy
      N(6),N(6)-dimethyl-3'-[O-methyltyrosylamido]adenosine), its 2',3'-regioisomer and
      a 3'-cytidyl-5'-(2'-deoxyfluoro)puromycyl dinucleotide analogue were synthesized
      following an approach involving i) the diastereospecific nitrite-assisted
      formation of a lyxo nucleosidic 2',3'-epoxide from an adenosine-2',3'-ditriflate
      derivative in a biphasic solvent mixture; ii) the regio- and stereoselective
      epoxide ring opening with sodium azide under mildly acidic aqueous conditions,
      iii) the stereospecific introduction of the fluor atom using DAST and iv) the
      reaction between the nucleosidyl or dinucleotidyl azide and an active ester of
      the N-protected amino acid using highly efficient solution conditions for the
      Staudinger-Vilarrasa coupling, to obtain the corresponding carboxamide directly
      from the in situ formed iminophosphorane. This coupling reaction furnished
      sterically quite demanding amides in 94 % isolated yields under very mild
      conditions and should therefore be of a more general value. Under certain
      reaction conditions we isolated (amino)acyltriazene derivatives from which
      dinitrogen was not eliminated. These secondary products are trapped and
      stabilized witnesses of the first intermediate of the Staudinger reaction, the
      phosphatriazenes (phosphazides, triazaphosphadienes) which usually eliminate
      dinitrogen in situ and rapidly rearrange into iminophosphoranes, unless they are
      derived from conjugated or sterically bulky azides and phosphines. The
      acyltriazenes could either be thermally decomposed or converted to the
      corresponding N-alkyl carboxamides through proton-assisted elimination of
      dinitrogen. All compounds were carefully characterized through MS spectrometry,
      (1)H, (19)F, (31)P and (13)C NMR spectroscopy.

PMID- 17455188
TI  - Noncovalent interactions and internal dynamics in dimethoxymethane-water.
AB  - The millimeter-wave absorption and Fourier transform microwave spectra of five
      isotopologues of the 1:1 adduct of dimethoxymethane-water have been measured in
      supersonic expansions. Each rotational transition appears as a quintuplet, due to
      the internal rotation of the two methyl groups, which are nonequivalent in the
      adduct. The water moiety, linked asymmetrically to dimethoxymethane, behaves as a
      proton donor to one of its oxygen atoms and interferes with the internal rotation
      of the farther methyl group through a C...HO interaction. From the analysis of
      the observed splittings, the V(3) barriers to the internal rotation of the two
      methyl groups have been determined to be 6.83(8) and 6.19(8) kJ mol(-1). The
      hydrogen bond structural parameters have been determined, the O...HO and C...HO
      distances being 1.93(1) and 2.78(4) A, respectively.

PMID- 17455189
TI  - Topological study of pseudo-cubic hydrogen-bond networks in a binary system
      composed of primary ammonium carboxylates: an analogue of an ice cube.
AB  - Hierarchical classification and single-crystal X-ray analysis of unique pseudo
      cubic hydrogen-bond networks composed of primary ammonium carboxylates were
      carried out. The networks consist of four carboxylate anions and four primary
      ammonium cations at the corners of the cube, and twelve charge-assisted N--H...O
      hydrogen bonds on the sides of the cube. The configuration of the carboxylate
      anions generates topological diversity in the network. The results of this
      hierarchical classification showed that pseudo-cubic hydrogen-bond networks
      composed of primary ammonium carboxylates can form nine topologically different
      networks. These pseudo-cubic networks are a subset of the networks formed by
      octameric water in the form of an "ice cube". The classification system can be
      applied to other pseudo-cubic networks in a similar way. A survey of crystal
      structures based on combinations of triphenylacetic acid with various alkylamines
      (carbon numbers up to eight) and examination of the CSD (Cambridge Structural
      Database) showed eight salts that form such networks in their crystal structures.
      These structures are classified into six topologically different networks.
      Similar networks composed of other salts are also discussed from a topological
      point of view.

PMID- 17455190
TI  - Selective treatment of cancer: synthesis, biological evaluation and structural
      elucidation of novel analogues of the antibiotic CC-1065 and the duocarmycins.
AB  - Novel diastereomerically pure beta-D-galactosidic prodrugs (+)-12 a-e of the
      cytotoxic antibiotics CC-1065 and the duocarmycins were prepared for an antibody
      directed enzyme prodrug therapy (ADEPT) using 4 as a substrate via a radical
      cyclization to give rac-5 and rac-6 followed by a chromatographic resolution of
      the enantiomers of rac-5, glycosidation and linkage to the DNA-binding units 10 a
      e. These only slightly toxic compounds can be toxified enzymatically by an
      antibody-beta-D-galactosidase conjugate at the surface of malignant cells to give
      the cytotoxic drugs, which then alkylate DNA. The new prodrugs were tested in in
      vitro cytotoxicity assays showing excellent QIC(50) values of 4800 and 4300 for
      (+)-12 a and (+)-12 b, respectively. The absolute configuration of precursor (+)
      5 was determined by comparison of the experimental CD spectrum with the
      theoretically predicted CD spectra and by X-ray structure analysis.

PMID- 17455191
TI  - HTS, chemical hybridization, and drug design identify a chemically unique
      antituberculosis agent-coupling serendipity and rational approaches to drug
      discovery.

PMID- 17455192
TI  - Organometallic polymers assembled from cation-pi interactions: use of ferrocene
      as a ditopic linker within the homologous series [{(Me3Si)2NM}2.(Cp2Fe)]infinity
      (M=Na, K, Rb, Cs; Cp=cyclopentadienyl).
AB  - Addition of ferrocene to solutions of alkali metal hexamethyldisilazides M(HMDS)
      in arenes (in which M=Na, K, Rb, Cs) allows the subsequent crystallization of the
      homologous series of compounds [{(Me(3)Si)(2)NM}(2) (Cp(2)Fe)](infinity) (1-4).
      Similar reactions using LiHMDS led to the recrystallization of the starting
      materials. The crystal structures of 1-4 reveal the formation of one-dimensional
      chains composed of dimeric [{M(HMDS)}(2)] aggregates, which are bridged through
      neutral ferrocene molecules by eta(5)-cation-pi interactions. In addition,
      compounds 3 and 4 also contain interchain agostic M--C interactions, producing
      two-dimensional 4(4)-nets. Whereas 1 and 2 were prepared from toluene, the
      syntheses of 3 and 4 required the use of tert-butylbenzene as the reaction media.
      The attempted crystallization of 3 and 4 from toluene resulted in formation of
      the mixed toluene/ferrocene solvated complexes [{(Me(3)Si)(2)NM)(2)}(2)
      (Cp(2)Fe)(x)(Tol)(y)](infinity) (in which M=Rb, x=0.6, y=0.8, 5; M=Cs, x=0.5,
      y=1, 6). The extended solid-state structures of 5 and 6 are closely related to
      the 4(4)-sheets 3 and 4, but are now assembled from a combination of cation-pi,
      agostic, and pi-pi interactions. The charge-separated complex
      [K{(C(6)H(6))(2)Cr}(1.5)(Mes)][Mg(HMDS)(3)] (15) was also structurally
      characterized and found to adopt an anionic two-dimensional 6(3)-network through
      doubly eta(3)-coordinated bis(benzene)chromium molecules. DFT calculations at the
      B3 LYP/6-31G* level of theory indicate that the binding energies of both
      ferrocene and toluene to the M(HMDS) dimers increases in the sequence Li<Na<K.
      This pattern is a consequence of the larger metals allowing more open
      coordination spheres to support cation-pi contacts. By comparison, binding of the
      isolated metal cations to the aromatic groups follow the reverse order K<Na<Li. A
      combined analysis of theoretical and experimental data suggest that ferrocene is
      a stronger cation-pi donor than toluene for the lighter metals, but that this
      difference is eliminated on descending the group.

PMID- 17455193
TI  - Loss of input from the mossy cells blocks maturation of newly generated granule
      cells.
AB  - The objective of this work is to check whether the input from the mossy cells to
      the inner molecular layer is necessary for the integration and maturation of the
      newly generated granule cells of the dentate gyrus (DG) in mice, and if after
      status epilepticus the sprouting of the mossy fibers can substitute for this
      projection. Newly generated cells were labeled by administration of 5-bromo
      deoxyuridine either before or after pilocarpine administration. The neuronal loss
      in the hippocampus after administration of pilocarpine combined with scopolamine
      and diazepam seemed restricted to the hilar mossy cells. The maturation of the
      granule cells was studied using immunohistochemistry for calretinin and NeuN in
      combination with detection of 5-bromo-deoxyuridine. The sprouting of the mossy
      fibers was detected using Timm staining for zinc-rich boutons. In normal
      conditions, granule cells took about 2 weeks to lose the immature marker
      calretinin. After the loss of the mossy cells, newly generated granule cells
      remained expressing calretinin for more than a month, until the sprouting of the
      mossy fibers substituted for the projection of the mossy cells in the inner
      molecular layer of the DG. Therefore, a proper pattern of connectivity is
      necessary for the normal development and integration of newly generated granule
      cells in the adult brain. In a changed environment they cannot adapt transforming
      in other cell types; simply they are unable to mature. The sprouting of the mossy
      fibers, although aberrant and a probable source of epileptic activity, may be
      important for the correct physiology of the granule cells, restoring a likeness
      of normality in their connective environment. The survival of granule cells
      incorporated as mature neurons was increased after pilocarpine when compared with
      normal conditions. Thus, it is likely that the reorganization of the circuitry
      after the loss of the mossy cells facilitates the survival and incorporation of
      the newly generated granule cells.

PMID- 17455194
TI  - The essentiality of PKCalpha and PKCbetaI translocation for CD14+monocyte
      differentiation towards macrophages and dendritic cells, respectively.
AB  - Human peripheral CD14(+)monocytes have been known to differentiate into monocyte
      derived macrophages (MDMs) or dendritic cells (MoDCs) upon suitable stimulation.
      However, the key intracellular molecule(s) associated with their differentiation
      towards specific cell types was(were) not fully understood. This study was
      designated to determine the association of PKC isoenzymes with the
      differentiation of CD14(+)monocytes into MDMs or MoDCs. Purified human peripheral
      CD14(+)monocytes were cultured with GM-CSF, or GM-CSF plus IL-4 for 7 days to
      induce cell differentiation. The phenotypic changes were analyzed by Flow
      Cytometry using various specific antibodies to cell type-specific surface
      markers. The immunological functions of these differentiated cells were
      determined by measuring the amounts of TNF-alpha secretion for MDMs, and the
      capacities of antigen-capturing and bacterial phagocytosis for MoDCs. The
      translocations of PKC isoenzymes in these cells from cytosol to plasma membrane
      were examined by Western Blot analysis and Confocal Microscopic observation. The
      treatment of CD14(+)monocytes with either GM-CSF or PMA elicited PKCalpha
      translocation and consequently induced their differentiation into MDMs. The
      inclusion of PKCalpha/beta(I) specific inhibitor, Go6976, greatly inhibited the
      GM-CSF-induced PKCalpha translocation and dose-dependently reduced the GM-CSF-
      induced MDM differentiation. On the other hand, the simultaneous pretreatment of
      CD14(+)monocytes with Go6976 and PKCbeta-specific inhibitor predominantly
      suppressed the GM-CSF/IL-4-induced generation of MoDCs. Further study
      demonstrated that GM-CSF/IL-4 selectively induced the translocation of
      PKCbeta(I), not PKCalpha or PKCbeta(II), in CD14(+)monocytes. In conclusion, the
      cell fate commitment of CD14(+)monocytes towards MDMs or MoDCs appears to be
      steered by the selective activation of PKCalpha or PKCbeta(I), respectively.

PMID- 17455195
TI  - A proximal direct repeat motif characterized as a negative regulatory element in
      the human renin gene.
AB  - The regulation of renin gene expression is thought to be fundamental to
      regulation of the total renin-angiotensin system. The human renin gene contains a
      direct repeat (DR) motif AGGGGTCAC-AGGGCCA in the proximal region (-259/-245 bp),
      which contains similar sequence for nuclear receptor superfamily binding core
      motif, AGGTCA, and is the most similar to COUP-TFII consensus. The DR motif was
      evaluated as a functional cis-element with renal cortex and chorio-decidual cells
      by footprint assay, electromobility shift assay (EMSA) and reporter assay. The DR
      motif site was protected by footprint analysis with a clear hypersensitive and a
      minor hypersensitive region in good accordance with the DR of the consensus. One
      of the binding proteins was strongly suspected to be COUP-TFII-consensus-specific
      by EMSA. The DNA/protein complexes obtained with nuclear extract of renin
      producing cells could be completely blocked by homologous competitor and strongly
      blocked by the second-half mutant oligonucleotide of the DR motif but not by the
      first-half mutant oligonucleotide. Finally, the transcriptional activity of
      second-half mutant construct is slightly elevated and that first-half mutant
      construct is significantly stronger by twofold compared with wild type construct
      in reporter assay. These findings suggest that the DR motif site of the human
      renin gene functions as a negative regulatory element involved in a twofold
      repression of transcription and that member(s) of nucleic receptor superfamily
      bind the site and play important roles in the human renin gene expression with a
      possibility that one of the binding protein is COUP-TFII.

PMID- 17455196
TI  - Telomere length status of somatic cell sheep clones and their offspring.
AB  - This study was carried out to determine the telomere length status of sheep
      clones and their offspring, and to examine telomere dynamics and chromosomal
      abnormalities in culture propagated donor cells. Skin samples were collected from
      somatic cell nuclear transfer-derived sheep clones, and three of their progeny
      generated by natural mating. Samples were collected from control animals (n =
      35), spanning in age from 1 month to 36 months of age. Genomic DNA was extracted
      from cell/tissue samples and their telomere lengths were assessed by terminal
      restriction fragment (TRF) analysis. Results revealed: that (a) sheep clones
      derived from cultured somatic cells have shortened telomere lengths compared to
      age-matched controls; (b) the offspring derived from natural mating between
      clones had normal telomere lengths compared to their age-matched counterparts;
      and donor cell cultures beyond 20 population doublings had significantly (P <
      0.05) shortened telomeres and exhibited a higher numerical and structural
      chromosomal abnormalities.

PMID- 17455197
TI  - Unreinforced spatial (latent) learning is mediated by a circuit that includes
      dorsal entorhinal cortex and fimbria fornix.
AB  - The relationship of the entorhinal cortex (EC) and fimbria-fornix (FF) in
      unreinforced spatial (latent) learning was studied using the conditioned-cue
      preference task on an eight-arm radial maze. The maze was turned before every
      trial to eliminate the use of local cues. During three pre-exposure sessions,
      food-deprived rats explored the center platform and two adjacent arms of the
      maze. Since most of the same cues were visible from both arm locations,
      discriminating them required spatial learning. The rats were then alternately
      confined to the end of each arm over several days: one arm always contained food,
      the other was empty. Finally, the rats were allowed free access to both arms with
      no food present. Normal rats spent more time in their food-paired than in their
      unpaired arms showing that they learned to discriminate between the arm
      locations. Bilateral micro-injections of muscimol into the dorsal, but not into
      the ventral EC, given before the pre-exposure sessions only, impaired the
      discrimination. The discrimination was also impaired in rats with unilateral
      lesions of FF and contralateral injections of muscimol into the dorsal EC given
      before the pre-exposure sessions. Ipsilateral FF lesions and entorhinal
      inactivation had no effect. These results indicate that the acquisition of
      information during unreinforced exploration of a novel environment requires an
      intact circuit involving the dorsal EC and fimbria fornix. Together with previous
      reports, that this form of learning does not require a functional hippocampus,
      (Gaskin et al. (2005) Hippocampus 15:1085-1093) the findings also suggest that
      the acquisition of certain kinds of unreinforced information by this circuit is
      independent of the hippocampus.

PMID- 17455198
TI  - Human hippocampal-dependent tasks: is awareness necessary or sufficient?
AB  - The hippocampus has been shown to be required for the acquisition of declarative
      or explicit memory. Whether all hippocampal-dependent forms of learning and
      memory are explicit is an open question. Controversy has emerged about the
      existence of implicit hippocampal-dependent tasks. Two implicit tasks that may
      involve the hippocampusare a relational eye tracking task (Ryan et al. (2000)
      Psychol Sci 11:454-461) and transitive inference (Greene et al. (2006) J Cognit
      Neurosci 18:1156-1173; Greene et al. (2001) Mem Cognit 29:893-902). Recently, it
      was shown that both of these tasks may depend upon task awareness (Smith et al.
      (2006) J Neurosci 26:11304-11312; Smith and Squire (2005) J Neurosci 25:10138
      10146). It is argued that in both cases, distinct, explicit versions of the tasks
      were created, which do not disprove the implicit nature of the original tasks.

PMID- 17455199
TI  - Using the wild bootstrap to quantify uncertainty in diffusion tensor imaging.
AB  - Estimation of noise-induced variability in diffusion tensor imaging (DTI) is
      needed to objectively follow disease progression in therapeutic monitoring and to
      provide consistent readouts of pathophysiology. The noise variability of
      nonlinear quantities of the diffusion tensor (e.g., fractional anisotropy, fiber
      orientation, etc.) have been quantified using the bootstrap, in which the data
      are resampled from the experimental averages, yet this approach is only
      applicable to DTI scans that contain multiple averages from the same sampling
      direction. It has been shown that DTI acquisitions with a modest to large number
      of directions, in which each direction is only sampled once, outperform the
      multiple averages approach. These acquisitions resist the traditional (regular)
      bootstrap analysis though. In contrast to the regular bootstrap, the wild
      bootstrap method can be applied to such protocols in which there is only one
      observation per direction. Here, we compare and contrast the wild bootstrap with
      the regular bootstrap using Monte Carlo numerical simulations for a number of
      diffusion scenarios. The regular and wild bootstrap methods are applied to human
      DTI data and empirical distributions are obtained for fractional anisotropy and
      the diffusion tensor eigensystem. Spatial maps of the estimated variability in
      the diffusion tensor principal eigenvector are provided. The wild bootstrap
      method can provide empirical distributions for tensor-derived quantities, such as
      fractional anisotropy and principal eigenvector direction, even when the exact
      distributions are not easily derived.

PMID- 17455200
TI  - Characterization of cecal gene expression in a differentially susceptible mouse
      model of bacterial-induced inflammatory bowel disease.
AB  - BACKGROUND: A/JCr mice develop typhlitis in response to Helicobacter hepaticus
      infection, whereas C57BL/6 mice coexist with this bacterium in a "commensal"
      relationship and do not develop disease even during prolonged colonization.
      METHODS: To determine mechanisms that control this balance between responsiveness
      and nonresponsiveness, the mucosal response of A/JCr and C57BL/6 mice to acute H.
      hepaticus colonization was evaluated using genome-wide profiling. Transcription
      levels for a subset of gene discoveries were then evaluated longitudinally by
      semiquantitative real-time reverse-transcriptase polymerase chain reaction (RT
      PCR) to identify changes in gene expression that occur during progression from
      the acute to chronic phase of colonization. To determine whether chronic mucosal
      inflammation in A/JCr mice was mediated through a Th1 mechanism, as was inferred
      from the gene expression data, mice with typhlitis were treated with neutralizing
      antibody targeting IL-12/23p40 or IFN-gamma and the response to treatment was
      determined by cecal lesion severity and transcription of disease-related genes.
      RESULTS: A/JCr mice had a biphasic expression of proinflammatory genes that
      corresponded with the acute and chronic phases of disease. In contrast, C57BL/6
      mice exhibited a less robust acute transcriptional response that waned by day 30
      postinoculation. Sustained upregulation of proinflammatory signals and
      responsiveness to anti-IL-12/23p40 and anti-IFN-gamma antibody suggests that
      inflammation in A/JCr mice was mediated through a Th1 mechanism. Prolonged
      upregulation of SOCS3 during the acute response to colonization suggests that
      C57BL/6 mice maintain mucosal homeostasis, at least in part by attenuating
      responsiveness to cytokine signaling. CONCLUSIONS: Collectively, these findings
      provide a foundation for understanding the immunological mechanisms that confer
      resistance or susceptibility to H. hepaticus-induced typhlitis.

PMID- 17455201
TI  - Association of DLG5 variants with inflammatory bowel disease in the New Zealand
      Caucasian population and meta-analysis of the DLG5 R30Q variant.
AB  - BACKGROUND: Variants in the DLG5 gene have been associated with inflammatory
      bowel disease (IBD) in samples from some, but not all populations. In particular,
      2 nonsynonymous single-nucleotide polymorphisms (SNPs), R30Q (rs1248696) and
      P1371Q (rs2289310), have been associated with an increased risk of IBD, and a
      common haplotype (called haplotype "A") has been associated with reduced risk.
      METHODS: We genotyped R30Q, P1371Q, and a haplotype A tagging SNP (rs2289311) in
      a New Zealand Caucasian cohort of 389 Crohn's disease (CD) patients, 406
      ulcerative colitis (UC) patients, and 416 population controls. Each SNP was
      tested for association with disease susceptibility and clinical phenotypes. We
      also performed a meta-analysis of R30Q data from published association studies.
      RESULTS: The haplotype A tagging SNP was associated with reduced risk of IBD at
      the 0.05 significance level (P=0.036) with an allelic odds ratio of 0.83 (95%
      confidence interval [CI]: 0.69-0.99). Association with haplotype A was strongest
      (odds ratio approximately 0.57) in UC patients with familial IBD or
      extraintestinal manifestations. The R30Q and P1371Q polymorphisms were not
      significantly associated with UC, CD, or IBD. Analysis of male and female data
      did not find any gender-specific associations. Meta-analysis gave no evidence of
      association of R30Q with IBD. CONCLUSIONS: Meta-analysis demonstrates that the
      minor allele of R30Q is not a risk factor for IBD across populations. This study
      provides some evidence that DLG5 haplotype A is associated with reduced risk of
      IBD in the New Zealand Caucasian population, but this association will need to be
      replicated in an independent sample.

PMID- 17455202
TI  - Viscosity gradient within the mucus layer determines the mucosal barrier function
      and the spatial organization of the intestinal microbiota.
AB  - BACKGROUND: Migration is an important virulence factor for intestinal bacteria.
      However, the role of bacterial mobility in the penetration of viscous mucus and
      their spatial organization within the colon is relatively unknown. METHODS:
      Movements of fecal bacteria were assessed in gels of varying agarose
      concentrations and were compared with patterns of bacterial distribution observed
      in colons from conventional and Enterobacter cloacae-monoassociated mice.
      Bacteria were visualized using fluorescence in situ hybridization. RESULTS: Long
      curly bacteria moved best in moderate viscosity gels, short rods and cocci
      preferred a low viscous environment, whereas high viscosity immobilized all
      bacterial groups. The spatial distribution of bacteria in the murine colon was
      also shape- and not taxonomy-dependent, indicating the existence of vertical
      (surface to lumen) and longitudinal (proximal to distal colon) viscosity
      gradients within the mucus layer. Our results suggest that mucus viscosity is low
      in goblet cells, at the crypt basis and close to the intestinal lumen, whereas
      sites adjacent to the columnar epithelium have a high mucus viscosity. The mucus
      viscosity increased progressively toward the distal colon, separating bacteria
      selectively in the proximal colon and completely in the distal colon.
      CONCLUSIONS: The site-specific regulation of mucus secretion and dehydration make
      the mucus layer firm and impenetrable for bacteria in regions close to the
      intestinal mucosa but loose and lubricating in regions adjacent to the luminal
      contents. Selective control of mucus secretion and dehydration may prove to be a
      key factor in the management of chronic diseases in which intestinal pathogens
      are involved.

PMID- 17455203
TI  - Liver injury in inflammatory bowel disease: long-term follow-up study of 786
      patients.
AB  - BACKGROUND: The aim of the study was to evaluate the incidence of abnormality of
      liver tests (LTs) or hepatotoxicity in a large group of inflammatory bowel
      disease (IBD) patients and, specifically, to assess the incidence of azathioprine
      (AZA)/mercaptopurine (MP)-induced liver injury in a long-term follow-up study.
      METHODS: All consecutive IBD patients followed for at least 5 years were included
      in this retrospective study. LTs including alanine transaminase, aspartate
      transaminase, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin
      were periodically monitored. "Abnormality-of-LTs" was defined as LTs between N
      (upper limit of the normal range) and 2 N, and "liver injury/hepatotoxicity" as
      LTs>2 N. RESULTS: A total of 786 patients were included, and 138 received AZA/MP;
      120 patients (15%) and 39 (5%) presented abnormality of LTs or hepatotoxicity,
      respectively, during follow-up. The most frequent explanations were AZA/MP
      treatment and fatty liver disease. Among AZA/MP-treated patients (690 patient
      years follow-up) the incidence of abnormal LTs and hepatotoxicity was,
      respectively, 7.1% and 2.6% per patient-year. Most patients spontaneously
      normalized LTs despite maintaining AZA/MP. These drugs were withdrawn due to
      hepatotoxicity (LTs>5 N and lack of decrease despite 50% dose reduction) in 3.6%
      of the patients and all of them normalized LTs. CONCLUSIONS: In IBD patients, AZA
      or MP treatment induces abnormality of LTs in a relatively high proportion of the
      cases, but the development of true hepatotoxicity/liver injury is exceptional.
      Moreover, most of the cases of thiopurine-induced hepatotoxicity in IBD patients
      are mild, and the abnormalities in LTs spontaneously return to normal values
      despite AZA/MP being maintained, therapy withdrawal being necessary in only
      approximately 4% of the patients.

PMID- 17455204
TI  - Probiotics for Crohn's disease: are they all alike?

PMID- 17455205
TI  - Terminal restriction fragment length polymorphism analysis of the diversity of
      fecal microbiota in patients with ulcerative colitis.
AB  - BACKGROUND: Terminal restriction fragment length polymorphism (T-RFLP) analysis
      is a powerful tool to assess the diversity of complexed microbiota. This permits
      rapid comparison of microbiota from many samples. In this study, we performed T
      RFLP analysis of the fecal microbiota from patients with ulcerative colitis (UC).
      METHODS: Forty-four patients with UC (23 women and 21 men, median age 25 years)
      and 46 healthy individuals (25 women and 21 men, median age 34 years) were
      enrolled in this study. DNA was extracted from their stool samples, and the 16S
      rRNA genes were amplified by PCR. The PCR products were then digested with HhaI
      and/or MspI restriction enzymes, and the length of the T-RF was determined.
      RESULTS: The fecal microbial communities were classified in 8 clusters. Almost
      all the healthy individuals (39 of 46) were included in cluster I, and most of
      the UC patients could be divided into the other 7 clusters, indicating that fecal
      bacterial communities are different between healthy individuals and active UC
      patients. Some T-RFs, derived from the unclassified bacteria, Ruminococcus,
      Eubacterium, Fusobacterium, gammaproteobacteria, unclassified Bacteroides, and
      unclassified Lactobacillus, were detected in the UC patients, but not in the
      healthy individuals. The T-RFLP patterns were also different between the active
      patients and inactive (remission) patients. The T-RF derived from the
      unclassified bacteria, Ruminococcus and Eubacterium, and the T-RFs derived from
      the unclassified bacteria, Eubacterium, and Fusobacterium were predominantly
      detected in the active patients not the inactive patients. In contrast, the T-RFs
      derived from Lactobacillus and unclassified Lactobacillus were more predominant
      in the inactive (remission) patients. In 4 patients with proctitis, the pattern
      of fecal microbial diversity was very similar. CONCLUSIONS: T-RFLP analyses
      showed that the diversity of fecal microbiota in patients with UC was different
      from that in healthy individuals. Unclassified bacteria, as well as known
      bacteria, can contribute to alterations in the bacterial diversity of UC
      patients.

PMID- 17455206
TI  - Confirmation of the role of ATG16L1 as a Crohn's disease susceptibility gene.
AB  - BACKGROUND: A German genome-wide nonsynonymous single nucleotide polymorphism
      (nsSNP) association study identified ATG16L1 as a Crohn's disease (CD)
      susceptibility gene. The association appeared to be confined to the nsSNP
      rs2,241,880 and was confirmed in 2 German independent case-control collections
      (combined P = 4.0 x 10(-8), odds ratio [OR] 1.45; 95% confidence interval [CI]:
      1.21-1.74), a CD transmission disequilibrium test (TDT) collection, and an
      independent UK cohort. A weak statistical interaction with CARD15 was
      demonstrated. No association with ulcerative colitis (UC) was demonstrated. The
      aims of the study were to replicate the association with CD, examine subphenotype
      associations and statistical interactions with CARD15, IL23R, and the IBD5 risk
      haplotype, as well as explore the association with UC. METHODS: The study
      included 645 CD and 676 UC rigorously phenotyped patients recruited from a single
      UK center. Unaffected controls comprised either spouses of patients (141) or
      individuals recruited from well-person clinics (1,049). The nsSNP rs2,241,880 was
      genotyped using MassArray (Sequenom). RESULTS: A strong association with CD was
      demonstrated (P = 2.33 x 10(-7), OR 1.45 [1.25-1.67]), but no significant
      association was demonstrated with any subphenotype. We failed to replicate the
      reported interaction between rs2,241,880 and the CARD15 low-risk haplotypes dd
      and Dd. No significant statistical interaction with the 3 known CD susceptibility
      genes was seen. No association with UC susceptibility (P = 0.37, OR 1.06 [0.93
      1.22]), or any UC subphenotype was identified. CONCLUSIONS: We confirmed the
      findings that ATG16L1 is a CD susceptibility gene and found no evidence of
      interaction with CARD15, IL23R, or IBD5.

PMID- 17455207
TI  - Effect of weekend 5-aminosalicylic acid (mesalazine) enema as maintenance therapy
      for ulcerative colitis: results from a randomized controlled study.
AB  - BACKGROUND: 5-aminosalicylic acid (5-ASA) is known to be effective in the
      treatment of active ulcerative colitis (UC). The aim of the current study was to
      investigate the effect of 5-ASA enemas, as a maintenance therapy for UC, when
      administered twice weekly as a weekend treatment regimen, compared to daily oral
      5-ASA alone. We hypothesized that the weekend enema therapy would be better
      tolerated by patients who worked or attended school. METHODS: Between January
      2004 and August 2005, patients with UC, in whom remission of the condition had
      just been induced, were randomly assigned to either: the weekend 5-ASA enema
      group (n=11), who received 1 g 5-ASA enemas twice a week on Saturday and Sunday
      plus oral 5-ASA 3 g/day for 7 days, or to the daily oral 5-ASA use only group
      (n=13), who received only oral 5-ASA 3 g/day for 7 days. The primary endpoint of
      the study was defined as the incidence of relapse. The study was stopped after 24
      patients had been enrolled because an interim analysis showed a significant
      benefit of the weekend 5-ASA enema group. RESULTS: In the weekend enema group, 2
      patients (18.2%) had relapses compared with 10 (76.9%) in the oral 5-ASA only
      group. The multivariate hazard ratio of relapse associated with weekend 5-ASA
      enema, relative to the oral alone group, was 0.19 (95% confidence interval, 0.04
      0.94). CONCLUSIONS: This study demonstrated the beneficial effects of adding
      weekend 1 g 5-ASA enema to daily 3 g oral 5-ASA as maintenance therapy for UC.

PMID- 17455208
TI  - "New drugs: kids come first": children should be included in trials of new
      biological treatments.
AB  - The advent of biological therapies has dramatically revolutionized the treatment
      options for refractory inflammatory bowel disease (IBD). Of all the biologics
      evaluated to date, infliximab, an anti-tumor necrosis factor-alpha monoclonal
      chimeric antibody, has been shown to be an extremely potent drug for acute and
      maintenance treatment of both adult and pediatric patients with severe IBD,
      especially in those with Crohn's disease, whereas other biological agents are
      undergoing evaluation in several clinical trials. Although infliximab has
      preferentially been used as rescue therapy for IBD patients refractory to
      traditional drugs, clinical and immunological arguments seem to indicate that the
      biological agents are an advantageous treatment for children with IBD when given
      early in the course of the disease. This, however, requires multicenter
      randomized controlled trials to prove.

PMID- 17455209
TI  - Quality of life after surgery, external beam irradiation, or brachytherapy for
      early-stage prostate cancer.
AB  - BACKGROUND: The primary treatments for clinically localized prostate cancer
      confer equivalent cancer control for most patients but disparate side effects. In
      the current study, the authors sought to compare health-related quality of life
      (HRQOL) outcomes after the most commonly used treatments. METHODS: A total of 580
      men completed the Medical Outcomes Study Short Form-36, the University of
      California-Los Angeles (UCLA) Prostate Cancer Index, and the American Urological
      Association Symptom Index before and through 24 months after treatment with
      radical prostatectomy (RP), external beam radiation therapy (EBRT), or
      brachytherapy (BT). RESULTS: General HRQOL did not appear to be affected by
      treatment. Obstructive and irritative urinary symptoms were more common after BT
      (P<.001). Urinary control and sexual function were better after EBRT than BT
      (P<.001 and P=.02, respectively) and better after BT than RP (P<.001 and P=.01,
      respectively). Among potent men, recovery of sexual function was best after EBRT
      and was equivalent after bilateral nerve-sparing surgery or BT. Sexual bother was
      more common than urinary or bowel bother after all 3 treatments. Bowel
      dysfunction was more common after EBRT or BT than RP (P<.001). CONCLUSIONS: In
      the current study, treatment for localized prostate cancer was found to
      differentially affect HRQOL outcomes. Urinary control and sexual function were
      better after EBRT, although bilateral nerve-sparing surgery diminished these
      differences among potent men undergoing RP. BT caused more obstructive and
      irritative symptoms, while both forms of radiation caused more bowel dysfunction.
      These results may inform medical decision-making in men with localized prostate
      cancer.

PMID- 17455210
TI  - Nmp4/CIZ contributes to fluid shear stress induced MMP-13 gene induction in
      osteoblasts.
AB  - The expression of matrix metalloproteinase-13 (MMP-13), involved in bone
      turnover, is elevated in stretched MC3T3-E1 osteoblast-like cells. Strain
      mediated forces impact bone remodeling due in large part to the movement of fluid
      through the canalicular-lacunar network. The resulting fluid shear stress (FSS)
      over the surface membranes of bone cells initiates bone remodeling. Although the
      nuclear events mediating putative FSS-induced changes in osteoblast MMP-13
      transcription are unknown, previous studies with bone cells suggest an overlap
      between osteoblast FSS- and PTH-induced signal response pathways. MMP-13 PTH
      response is regulated by a 110 bp 5' regulatory region, conserved across the
      mouse, rat, and human genes, that supports the binding of numerous transcription
      factors including Runx2, c-fos/c-jun, Ets-1, and nuclear matrix protein 4/cas
      interacting zinc finger protein (Nmp4/CIZ) a nucleocytoplasmic shuttling trans
      acting protein that attenuates PTH-driven transcription. Nmp4/CIZ also binds
      p130(cas), an adaptor protein implicated in mechanotransduction. Here we sought
      to determine whether Nmp4/CIZ contributes to FSS-induced changes in MMP-13
      transcription. FSS (12 dynes/cm(2), 3-5 h) increased MMP-13 promoter-reporter
      activity approximately two-fold in MC3T3-E1 osteoblast-like cells attended by a
      comparable increase in mRNA expression. This was accompanied by a decrease in
      Nmp4/CIZ binding to its cis-element within the PTH response region, the mutation
      of which abrogated the MMP-13 response to FSS. Interestingly, FSS enhanced
      Nmp4/CIZ promoter activity and induced p130(cas) nuclear translocation. We
      conclude that the PTH regulatory region of MMP-13 also contributes to FSS
      response and that Nmp4/CIZ plays similar but distinct roles in mediating hormone-
      and FSS-driven induction of MMP-13 in bone cells.

PMID- 17455211
TI  - RIF-1, a novel nuclear receptor corepressor that associates with the nuclear
      matrix.
AB  - The retinoic acid receptors (RARs) are ligand-dependent transcription factors
      that play critical roles in cell differentiation, embryonic development, and
      tumor suppression. RAR transcriptional activities are mediated by a growing
      family of nuclear receptor (NR) coregulators. Here we report the cloning and
      characterization of a novel protein RIF1 (receptor interacting factor) that
      interacts with RARalpha in vivo and in vitro. RIF1 encodes a novel 739 amino acid
      protein that is ubiquitously expressed in a variety of tissues and cell lines.
      GST-pull down assays show that RIF1 also interacts with a number of other NRs.
      The interaction domain of RIF1 for RARalpha is located at the C-terminal region
      of RIF1, between amino acids 512 and 674. RIF1 is localized exclusively in the
      cell nucleus and specifically to the nuclear matrix. Mutation of the nuclear
      localization signal abolishes this nuclear localization and causes RIF1 to appear
      in the cytoplasm. Co-transfection of RIF1 with RAR causes RAR to localize to the
      nuclear matrix. RIF1 contains a strong transcriptional repression domain that
      robustly inhibits ligand-dependent transcriptional activation by RARalpha. This
      domain is located to the distal C-terminal 100 amino acids, distinct from the
      RARalpha-interaction and nuclear matrix-targeting domains. The transcriptional
      repression activity of RIF1 is mediated at least in part through direct
      recruitment of histone deacetylases. This study identifies RIF1 as a novel
      nuclear matrix transcription repressor, and suggests a potential role of RIF1
      that regulates NR transcriptional activity.

PMID- 17455212
TI  - Polymorphisms in dopamine receptor DRD1 and DRD2 genes and psychopathological and
      extrapyramidal symptoms in patients on long-term antipsychotic treatment.
AB  - DRD(1) and DRD(2) receptor gene variants have been associated with clinical
      aspects of schizophrenia; however only specific features were analyzed in
      different samples. To assess the complex interaction between genetic and clinical
      factors, we studied the possible cross-interactions between DRD1 and DRD2
      dopamine receptor gene polymorphisms, symptomatology of schizophrenia and
      schizoaffective disorders, and the occurrence of treatment induced side effects
      taking into consideration possible clinical confounding variables. One hundred
      thirty one outpatients in stable remission meeting the DSMIV criteria for
      schizophrenia spectrum disorders and receiving long-term maintenance therapy with
      haloperidol, fluphenazine, zuclopenthixole, or risperidone were genotyped for
      DRD1 A-48G, DRD2 Ins-141CDel, and DRD2 Ser311Cys polymorphisms.
      Psychopathological symptoms were assessed with the positive and negative syndrome
      scale for schizophrenia (PANSS). Extrapyramidal side effects were assessed with
      the Simpson-Angus extrapyramidal side effects scale (EPS), the Barnes Akathisia
      scale (BARS), and the abnormal involuntary movement scale (AIMS). Drug dosage was
      included as covariant because it was associated with the severity of
      symptomatology, akathisia, and parkinsonism. No association was observed for DRD1
      and DRD2 polymorphisms and extrapyramidal side effects, or with the other
      clinical variables considered. Our study suggests that DRD1 and DRD2 variants are
      not liability factors for tardive dyskinesia.

PMID- 17455213
TI  - Investigation of variation in SNAP-25 and ADHD and relationship to co-morbid
      major depressive disorder.
AB  - Synaptosomal-associated protein of 25 kDa (SNAP-25), a protein involved in
      presynaptic neurotransmitter release, is a candidate gene for attention
      deficit/hyperactivity disorder (ADHD). Previous investigators have reported
      association initially with two single nucleotide polymorphisms (SNPs) (rs3746544,
      rs1051312) and their associated haplotypes. Subsequently, additional SNPs across
      the region were also reported to be associated with ADHD. We attempted to
      replicate these observations in a sample of 229 families with ADHD offspring by
      genotyping 61 SNPs spanning the region containing SNAP-25. A single SNP
      (rs3787283) which is in strong linkage disequilibrium (LD) with rs3746544 and
      rs1051312 (D' = 0.89-0.94) resulted in a nominally significant association (P =
      0.002). When we pooled our data with those from prior studies, results were
      modestly significant for rs3746544 (P = 0.048) and rs6077690 (P = 0.031). As an
      attempt to determine if specific ADHD-related phenotypes may be more relevant to
      SNAP-25 than the categorical diagnosis, we carried out exploratory subgroup
      analysis in our ADHD sample according to co-morbid status. We found the strongest
      association result in the ADHD patients with co-morbid major depressive disorder
      (MDD). Six SNPs were nominally associated with the ADHD and co-morbid MDD cases
      (P = 0.012-0.045). Furthermore, a haplotype block located 11 kb 3' of the gene
      showed positive evidence for association with this phenotype (global P = 0.013).
      In conclusion, we report some evidence supporting the association of previously
      implicated SNPs (rs3746544, rs1051312) of SNAP-25 to ADHD. We further suggest
      that co-morbidity with MDD may enhance detection of the association between SNAP
      25 and ADHD.

PMID- 17455214
TI  - Genome-wide scan of bipolar disorder and investigation of population
      stratification effects on linkage: support for susceptibility loci at 4q21, 7q36,
      9p21, 12q24, 14q24, and 16p13.
AB  - Bipolar disorder (BPD) is a complex genetic disorder with cycling symptoms of
      depression and mania. Despite the extreme complexity of this psychiatric
      disorder, attempts to localize genes which confer vulnerability to the disorder
      have had some success. Chromosomal regions including 4p16, 12q24, 18p11, 18q22,
      and 21q21 have been repeatedly linked to BPD in different populations. Here we
      present the results of a whole genome scan for linkage to BPD in an Irish
      population. Our most significant result was at 14q24 which yielded a non
      parametric LOD (NPL) score of 3.27 at the D14S588 marker with a nominal P-value
      of 0.0006 under a narrow (bipolar type I only) model of affection. We previously
      reported linkage to 14q22-24 in a subset of the families tested in this analysis.
      We also obtained suggestive evidence for linkage at 4q21, 9p21, 12q24, and 16p13,
      chromosomal regions that have all been previously linked to BPD. Additionally, we
      report on a novel approach to linkage analysis, STRUCTURE-Guided Linkage Analysis
      (SGLA), which is designed to reduce genetic heterogeneity and increase the power
      to detect linkage. Application of this technique resulted in more highly
      significant evidence for linkage of BPD to three regions including 16p13, a locus
      that has been repeatedly linked to numerous psychiatric disorders.

PMID- 17455215
TI  - Relationship of 5-HTTLPR genotypes and depression risk in the presence of trauma
      in a female twin sample.
AB  - Several studies have implicated an insertion/deletion polymorphism in the
      promoter region of the serotonin transporter gene (SLC6A4; 5-HTT) in the
      development of mood disorders. In the present study of a sample of 247 young
      adult female twins from Missouri, we examine whether this polymorphism interacts
      with the effect of adverse life events to increase risk for developing
      depression. We found a significant interaction between the number of high
      activity L(A) alleles and exposure to trauma (OR = 1.70, P < 0.0001). This
      differs from previous reports, in that the higher activity genotypes (L(A)/L(A),
      L(A)/S, L(A)/L(G)), rather than the low activity genotypes (S/S, S/L(G),
      L(G)/L(G)), are associated with an increased incidence of major depressive
      disease (MDD) in the presence of environmental trauma.

PMID- 17455216
TI  - Biocompatibility evaluation of crosslinked chitosan hydrogels after subcutaneous
      and intraperitoneal implantation in the rat.
AB  - The aim of the present study was to evaluate the toxicity of biodegradable
      hydrogels in the rat with a future aim of utilizing this hydrogel as a vehicle
      for brachytherapy delivery in cancer patients. Two types of chitosan hydrogels:
      fast degrading and slow degrading; were prepared and surgically implanted in
      rats. The adjacent tissue response to the gels after subcutaneous and
      intraperitoneal implantation was examined histologically and found to be
      identical to typical foreign body response and was milder than the response to
      absorbable surgical sutures (Vicril). Neither tissue damage nor gel fragments
      could be detected in distant organs (brain, heart, lungs, liver, spleen, kidney,
      and sternal bone marrow) after implantation of the hydrogels. The degradation
      mechanism of the gels was studied in vivo, and it was deduced that an oxidative
      process degraded the chitosan. Loading the hydrogels with a radioisotope (131I
      norcholesterol) caused a severe tissue response and necrosis in adjacent tissues
      only at a distance of several microns. It is concluded that crosslinked chitosan
      implants could serve as alternative, biocompatible, and safe biodegradable
      devices for radioisotope delivery in brachytherapy for cancer.

PMID- 17455217
TI  - Regulation of endothelial cell function by GRGDSP peptide grafted on
      interpenetrating polymers.
AB  - Vascular endothelium plays an important role in preventing thrombogenesis.
      Bioactive molecules such as fibronectin-derived peptide Gly-Arg-Gly-Asp-Ser-Pro
      (GRGDSP) can be used to modify the surface of cardiovascular implants such as
      vascular grafts to promote endothelialization. Here we conjugated GRGDSP peptide
      to the nonfouling surface of an interpenetrating polymer network (IPN), and
      investigated the effects of the immobilized GRGDSP molecules on EC functions
      under static and flow conditions at well-defined GRGDSP surface densities
      (approximately 0 to 3 pmol/cm2). EC adhesion and spreading increased with GRGDSP
      surface density, reached a plateau at 1.5 pmol/cm2, and increased further beyond
      2.8 pmol/cm2. Cell adhesion and spreading on GRGDSP induced two waves of
      extracellular signal-regulated kinase (ERK) activation, and 0.2 pmol/cm2 density
      of GRGDSP was sufficient to activate ERK. EC proliferation rate was not sensitive
      to GRGDSP surface density, suggesting that cell spreading at low-density of
      GRGDSP is sufficient to maintain EC proliferation. EC migration on lower-density
      GRGDSP-IPN surfaces was faster under static condition. With the increase of
      GRGDSP density, the speed and persistence of EC migration dropped quickly (0.2
      0.8 pmol/cm2) and reached a plateau, followed by a slower and gradual decrease
      (1.5-3.0 pmol/cm2). These data suggest that the changes of EC functions were more
      sensitive to the increase of GRGDSP density at lower range. Under flow condition
      with shear stress at 12 dyn/cm2, EC migration was inhibited on GRGDSP-IPN
      surfaces, which may be attributed to the assembly of large focal adhesions
      induced by shear stress, suggesting a catch-bond characteristic for RGD-integrin
      binding. This study provides a rational base for surface engineering of
      cardiovascular implants.

PMID- 17455218
TI  - Cost-effectiveness of colorectal cancer screening with computed tomography
      colonography: the impact of not reporting diminutive lesions.
AB  - BACKGROUND: Prior cost-effectiveness models analyzing computed tomography
      colonography (CTC) screening have assumed that patients with diminutive lesions
      (<or=5 mm) will be referred to optical colonoscopy (OC) for polypectomy. However,
      consensus guidelines for CTC recommend reporting only polyps measuring >or=6 mm.
      The purpose of the current study was to assess the potential harms, benefits, and
      cost-effectiveness of CTC screening without the reporting of diminutive lesions
      compared with other screening strategies. METHODS: The cost-effectiveness of
      screening with CTC (with and without a 6-mm reporting threshold), OC, and
      flexible sigmoidoscopy (FS) were evaluated using a Markov model applied to a
      hypothetical cohort of 100,000 persons age 50 years. RESULTS: The model predicted
      an overall cost per life-year gained relative to no screening of $4361, $7138,
      $7407, and $9180, respectively, for CTC with a 6-mm reporting threshold, CTC with
      no threshold, FS, and OC. The incremental costs associated with reporting
      diminutive lesions at the time of CTC amounted to $118,440 per additional life
      year gained, whereas the incidence of colorectal cancer was reduced by only 1.3%
      (from 36.5% to 37.8%). Compared with primary OC screening, CTC with a 6-mm
      threshold resulted in a 77.6% reduction in invasive endoscopic procedures (39,374
      compared with 175,911) and 1112 fewer reported OC-related complications from
      perforation or bleeding. CONCLUSIONS: CTC with nonreporting of diminutive lesions
      was found to be the most cost-effective and safest screening option evaluated,
      thereby providing further support for this approach. Overall, the removal of
      diminutive lesions appears to carry an unjustified burden of costs and
      complications relative to the minimal gain in clinical efficacy.

PMID- 17455219
TI  - Meta-analysis of racial disparities in survival in association with socioeconomic
      status among men and women with colon cancer.
AB  - BACKGROUND: Few studies have addressed racial disparities in survival for colon
      cancer by adequately incorporating both treatment and socioeconomic factors, and
      the findings from those studies have been inconsistent. The objectives of the
      current study were to systematically review the existing literature and provide a
      more stable estimate of the measures of association between socioeconomic status
      and racial disparities in survival for colon cancer by undertaking a meta
      analysis. METHODS: For this meta-analysis, the authors searched the MEDLINE
      database to identify articles published in English from 1966 to August 2006 that
      met the following inclusion criteria: original research articles that addressed
      the association between race/ethnicity and survival in patients with colon or
      colorectal cancer after adjusting for socioeconomic status. In total, 66 full
      articles were reviewed, and 56 of those articles were excluded, which left 10
      studies for the final analysis. RESULTS: The pooled hazard ratio (HR) for African
      Americans compared with Caucasians was 1.14 (95% confidence interval [95% CI],
      1.00-1.29) for all-cause mortality and 1.13 (95% CI, 1.01-1.28) for colon cancer
      specific mortality. The test for homogeneity of the HR was statistically
      significant across the studies for all-cause mortality (Q=31.69; P<.001) but was
      not significant across the studies for colon cancer-specific mortality (Q=7.45;
      P=.114). CONCLUSIONS: Racial disparities in survival for colon cancer between
      African Americans and Caucasians were only marginally significant after adjusting
      for socioeconomic factors and treatment. Attempts to modify treatment and
      socioeconomic factors with the objective of reducing racial disparities in health
      outcomes may have important clinical and public health implications.

PMID- 17455220
TI  - Dextran-sulfate-adsorption of atherosclerotic lipoproteins from whole blood or
      separated plasma for lipid-apheresis--comparison of performance characteristics
      with DALI and Lipidfiltration.
AB  - For many years dextran sulfate adsorption (DSA) treatment of separated plasma has
      been an established technology for low-density lipoprotein (LDL)-elimination.
      Recently a system for the treatment of whole blood based on DSA was introduced
      into clinical practice. To further characterize DSA treatment of whole blood, the
      performance characteristics of both DSA modalities were compared at two
      investigational sites with two alternative LDL apheresis systems being already in
      routine clinical use. In prospective cross-over design, DSA whole blood treatment
      was compared with a whole blood polyacrylate LDL adsorption system (DALI) in one
      study group. DSA for plasma treatment was compared with Lipidfiltration in cross
      over design in a second study group. In total, 12 patients on chronic LDL
      apheresis received 169 treatments. Six patients were treated twice with whole
      blood polyacrylate adsorption and twice with whole blood DSA. LDL-cholesterol
      (74.9-78.0%) and lipoprotein (a) (72.1-73.3%) were reduced by both with equal
      efficacy. DSA achieved a significantly higher reduction rate of fibrinogen.
      Another six patients were treated eight times with DSA plasma adsorption followed
      by 16 Lipidfiltration treatments. LDL-cholesterol (67.0-70.2%) and lipoprotein
      (a) (69.2-73.7%) were reduced by both with equal efficacy. Fibrinogen was
      eliminated more efficiently by Lipidfiltration (50.2 vs. 38.5%). DSA proved to be
      a safe and effective in both treatment modes, for plasma as well as for whole
      blood. At the discretion of the apheresis specialist, depending upon the status
      of national approval, DSA of whole blood complements the armamentarium of
      powerful modalities for extracorporeal elimination of atherosclerotic
      lipoproteins to meet specific individual, medical, or logistic needs.

PMID- 17455221
TI  - Molecular description of a 3D in vitro model for the study of epithelial ovarian
      cancer (EOC).
AB  - Epithelial ovarian cancer (EOC) cell lines are useful tools for the molecular and
      biological characterization of ovarian cancer. The use of an in vitro
      multidimensional (3-D) culture model recapitulates some of the growth conditions
      encountered by tumor cells in vivo. Here we describe a molecular comparison of
      spheroid based 3D EOC models versus monolayer cultures and xenografts using cell
      lines from malignant ovarian tumors (TOV-21G and TOV-112D) and ascites (OV-90)
      previously established and characterized in our laboratory. Gene expression
      analyses of the three models were performed using the Affymetrix HG-U133A high
      density DNA array. Cluster analysis identified a set of genes that stratified
      expression profiles from the EOC cell lines grown as spheroids and xenografts
      from that of monolayer cultures. The gene expression analysis results were
      validated by Q-PCR analyses on an independent set of RNAs. Differential
      expression observed for the S100A6 gene between the monolayer, spheroid cultures
      and xenografts was confirmed at the protein level by immunohistochemistry. The
      analysis was extended to various ovarian tumor tissues using an EOC tissue array.
      This result represents an example of a gene that, if studied in vitro, is more
      representative of the in vivo disease in a 3D model rather than the monolayer
      culture. Identification of genes in spheroid models that mimic the in vivo tumor
      gene expression patterns may allow a better understanding of the community effect
      observed in human disease that is determined by direct or indirect interactions
      of cells with their environment or other surrounding cells.

PMID- 17455222
TI  - Constitutive collagenase-1 synthesis through MAPK pathways is mediated, in part,
      by endogenous IL-1alpha during fibrotic repair in corneal stroma.
AB  - Collagenase-1 is a protease expressed by active fibroblasts that is involved in
      remodeling of the extracellular matrix (ECM). In this study, we characterize the
      intracellular signaling mechanism of collagenase-1 production by IL-1alpha in
      subcultured normal fibroblasts (NF) from uninjured normal corneas, compared to
      that in repair wound fibroblasts (WF). In NF, collagenase-1 was induced
      specifically after the exogenous addition of IL-1alpha via activation of ERK and
      p38MAPK. Collagenase-1 expression was strongly suppressed upon treatment with
      either a MEK or p38MAPK inhibitor. In contrast, repair WF constitutively
      synthesized both IL-1alpha and collagenase-1. Combined treatment with both
      mitogen-activated protein kinase (MAPK) inhibitors dramatically reduced
      collagenase-1 synthesis, while individual MEK1 or p38 inhibitors weakly modulated
      the collagenase-1 level. The results indicate that both pathways are crucial in
      the regulation of collagenase-1 synthesis. Furthermore, an IL-1alpha receptor
      antagonist (IL-1ra) could not abolish constitutive collagenase-1 synthesis, even
      at high doses, suggesting that other cytokines/factors are additionally involved
      in this process. We propose that induction of collagenase-1 by IL-1alpha in both
      WF and NF depends on a unique combination of cell type-specific signaling
      pathways.

PMID- 17455223
TI  - Protein kinase Cdelta-mediated CREB activation regulates ghrelin-induced
      cyclooxygenase-2 expression and prostaglandin E2 production in human colonic
      epithelial cells.
AB  - Ghrelin, a newly identified gastric peptide, is known for its potent activity in
      growth hormone release and appetite. Our recent study showed that ghrelin could
      stimulate protein kinase C-mediated activation of nuclear factor-kappaB (NF
      kappaB) and interleukin-8 secretion in human colonic epithelial cells transfected
      with a functional ghrelin receptor. In the present study, the effect of ghrelin
      stimulation on cyclooxygenese-2 expression and prostaglandin E2 production was
      examined. The data indicate that ghrelin significantly increased the levels of
      cyclooxygenase-2 (COX-2) protein as well as its promoter activity, which leaded
      to profound increase in prostaglandin E2 secretion. In order to examine the
      involvement of NF-kappaB and cAMP responsive element-binding protein (CREB) in
      this response, the NF-kappaB inhibitory protein IkappaBalpha or a dominant
      negative mutant of CREB was co-transfected into cells and the data show that
      transfection of either IkappaBalpha or DN-CREB significantly attenuated ghrelin
      induced COX-2 expression. Moreover ghrelin stimulated phosphorylation of CREB,
      which was mediated primarily via protein kinase Cdelta activation. Furthermore,
      inhibition of PKCdelta function significantly attenuated ghrelin-induced COX-2
      expression. In addition, ghrelin stimulates phosphorylation of PKCdelta.
      Together, these results indicate that in addition to NF-kappaB, protein kinase
      Cdelta-mediated CREB activation plays an important role in the cellular responses
      of ghrelin.

PMID- 17455224
TI  - Early experience affects the traits of monogamy in a sexually dimorphic manner.
AB  - The goal of this study was to examine the effects of early life experiences on
      the subsequent expression of traits characteristic of social monogamy in prairie
      voles (Microtus ochrogaster). During cage changes parents and their offspring
      were either transferred between cages in a cup (zero manipulation, MAN0) or with
      a gloved hand (one manipulation, MAN1). Following weaning the offspring were
      tested for alloparental behavior. In adulthood they were tested for the capacity
      to form partner preferences, behavior in an elevated plus-maze (EPM), and
      corticosterone levels. MAN0 males (but not females) showed lower levels of
      alloparental behavior than MAN1 males. MAN0 females (but not males) were less
      likely to form pair bonds than MAN1 females. MAN0 animals of both sexes were less
      exploratory in the EPM than MAN1 counterparts. These experiments support the
      hypothesis that behaviors used to characterize monogamy are vulnerable in a sex
      specific manner to early experience.

PMID- 17455225
TI  - Early weaning decreases play-fighting behavior during the postweaning
      developmental period of Wistar rats.
AB  - We examined the influence of early weaning on the development of play-fighting
      behaviors and anxiety status in Wistar rats. Pups were divided into two groups,
      those weaned at postnatal day (PD) 16 (early-weaned group) and those weaned at
      PD30 (normally weaned group), and were housed in pairs of the same sex. Playful
      interactions were measured for each pair once a week from 4 to 7 weeks of age.
      Thereafter, during early adulthood, all the rats were subjected to the elevated
      plus-maze test. The frequencies of pinning and playful attack were less in the
      early-weaned group than in the normally weaned group. In the elevated plus-maze
      test, rat pups in the early-weaned group had higher anxiety levels. The results
      showed that deprivation of mother-pup interactions during the preweaning period
      decreases affiliative interactions between cage mates, including play-fighting
      behaviors during the postweaning developmental period, and increases anxiety
      levels during early adulthood.

PMID- 17455226
TI  - Social influences on formula intake via suckling in 7 to 14-week-old-infants.
AB  - To investigate social influences on human suckling behavior, 25 healthy, full
      term, 7 to 14-week-old infants were each bottle-fed their own formula twice by
      their mother and once in each of four experimental conditions: (a) held, provided
      social interaction; (b) held, without interaction; (c) not held, provided
      interaction; (d) not held, without interaction. Volume intake (VI), Total Sucks,
      infant gaze direction, and time elapsed since the last feeding were determined.
      There were three major findings: (1) social interaction increased VI; (2) VI was
      linearly related to the time since the last feeding in held infants; (3) Total
      Sucks and VI were both highly correlated with privation length when infants did
      not look at the feeder and when fed by the mother. Thus, social influences exert
      strong immediate impacts on suckling. Accordingly, suckling functions to obtain
      both nutrition from and social information about the feeder.

PMID- 17455227
TI  - Adult and peer influences on starling song development.
AB  - Adult influence on song development was rarely investigated in complex social
      settings. We investigated the influence of the young/adult ratio on song learning
      in European starlings. Starling songs are composed of two categories: whistles
      and warbling. Warbling includes three parts: complex variable motifs, click
      motifs, and high frequency motifs. Song learning by young birds raised in group
      (G birds), in group with adults (GT birds) or in pair with one adult (IT birds)
      were compared. Song tutor choice, song sharing, and song quality varied with
      social context. The mere presence of adults in a group was not sufficient for
      young to develop all adult song features. Only IT birds chose adults as tutors.
      Social contact with only one adult enhanced acquisition of whistles, click
      motifs, individuality, and reduced the number of high frequency motifs (adult
      song features). This study suggests that the adult influence is proportional to
      young/adult ratio.

PMID- 17455228
TI  - Increased expression and differential phosphorylation of stathmin may promote
      prostate cancer progression.
AB  - BACKGROUND: Proteins which regulate normal development may promote tumorigenesis,
      tumor progression, or metastasis through dysregulation of these functions. We
      postulate that proteins, which regulate prostate growth also promote prostate
      cancer (PCa) progression. METHODS: Two Dimensional Gel Electrophoresis was
      utilized to compare patterns of protein expression in 12T-7f prostates (LPB-Tag
      mouse model for PCa) during tumor development and progression with those of
      normal developing and adult wild type CD-1 prostates. Stathmin expression and
      phosphorylation patterns were analyzed in mouse and human PCa cell lines as well
      as in human PCa tissue arrays. RESULTS: Stathmin was identified by two
      dimensional gel electrophoresis and mass spectrometry. Stathmin levels increase
      early during normal mouse prostate development and again during prostate tumor
      development and progression. In human prostate adenocarcinoma, stathmin increases
      in Gleason pattern 5. Further, stathmin is differentially phosphorylated in
      androgen-dependent LNCaP cells compared to androgen-independent PC-3 and DU145
      cells. This differential phosphorylation is modulated by androgen and anti
      androgen treatment. CONCLUSION: Stathmin expression is highest when the prostate
      is undergoing morphogenesis or tumorigenesis and these processes may be regulated
      through differential phosphorylation. Furthermore, modulation of stathmin
      phosphorylation may correlate with the development of androgen-independent PCa.

PMID- 17455229
TI  - Cytochrome P450 2B6 is a growth-inhibitory and prognostic factor for prostate
      cancer.
AB  - BACKGROUND: Cytochrome P450s (CYPs) influence the biological effects of
      carcinogens, drugs and hormones including testosterones. Among them, Cytochrome
      P450 2B6 (CYP2B6) plays a critical role in the deactivation of testosterone. In
      the present study, we examined CYP2B6 expression in human prostate tissues and
      prostate cancer. METHODS: Immunohistochemical analysis was performed in 98 benign
      and 106 malignant prostate tissues and patients' charts were reviewed for
      clinical, pathologic and survival data. We also investigated whether stable
      expression of CYP2B6 in LNCaP (human prostate cancer cell line) influences
      cellular proliferation. RESULTS: CYP2B6 was abundantly expressed in the normal
      epithelial cells compared to the prostate cancer cells. Significant
      immunostaining of CYP2B6 was found in 75 of 106 samples (71%), in the cytoplasm
      of cancerous tissue samples. CYP2B6 immunoreactivity was inversely correlated
      with high Gleason score (P < 0.001). Decreased immunoreactivity of CYP2B6
      significantly correlated with poor prognosis (P < 0.0001). Univariate and
      multivariate hazard analyses revealed a significant correlation of decreased
      CYP2B6 expression with poor cancer-specific survival (P = 0.0028 and 0.0142,
      respectively). Furthermore, overexpression of CYP2B6 in LNCaP cells significantly
      decreased testosterone-induced proliferation. CONCLUSIONS: These results
      demonstrated that decreased expression of CYP2B6 might play a role in the
      development of prostate cancer, and be useful as the prognostic predictor for
      human prostate cancer.

PMID- 17455231
TI  - Mitochondrial DNA hypervariable region-1 sequence variation and phylogeny of the
      concolor gibbons, Nomascus.
AB  - The still little known concolor gibbons are represented by 14 taxa (five species,
      nine subspecies) distributed parapatrically in China, Myanmar, Vietnam, Laos and
      Cambodia. To set the stage for a phylogeographic study of the genus we examined
      DNA sequences from the highly variable mitochondrial hypervariable region-1 (HVR
      1 or control region) in 51 animals, mostly of unknown geographic provenance. We
      developed gibbon-specific primers to amplify mtDNA noninvasively and obtained
      >477 bp sequences from 38 gibbons in North American and European zoos and >159 bp
      sequences from ten Chinese museum skins. In hindsight, we believe these animals
      represent eight of the nine nominal subspecies and four of the five nominal
      species. Bayesian, maximum likelihood and maximum parsimony haplotype network
      analyses gave concordant results and show Nomascus to be monophyletic.
      Significant intraspecific variation within N. leucogenys (17 haplotypes) is
      comparable with that reported earlier in Hylobates lar and less than half the
      known interspecific pairwise distances in gibbons. Sequence data support the
      recognition of five species (concolor, leucogenys, nasutus, gabriellae and
      probably hainanus) and suggest that nasutus is the oldest and leucogenys, the
      youngest taxon. In contrast, the subspecies N. c. furvogaster, N. c.
      jingdongensis, and N. leucogenys siki, are not recognizable at this otherwise
      informative genetic locus. These results show that HVR-1 sequence is variable
      enough to define evolutionarily significant units in Nomascus and, if coupled
      with multilocus microsatellite or SNP genotyping, more than adequate to
      characterize their phylogeographic history. There is an urgent need to obtain DNA
      from gibbons of known geographic provenance before they are extirpated to
      facilitate the conservation genetic management of the surviving animals.

PMID- 17455230
TI  - Identification of HLA-DRB1*1501-restricted T-cell epitopes from human prostatic
      acid phosphatase.
AB  - BACKGROUND: The crucial role of CD4 T-cells in anti-tumor immune response is
      widely recognized, yet the identification of HLA class II-restricted epitopes
      derived from tumor antigens has lagged behind compared to class I epitopes. This
      is particularly true for prostate cancer. Based on the hypothesis that successful
      cancer immunotherapy will likely resemble autoimmunity, we searched for the CD4 T
      cell epitopes derived from prostatic proteins that are restricted by human
      leukocyte antigen (HLA)-DRB1*1501, an allele associated with granulomatous
      prostatitis (GP), a disease that may have an autoimmune etiology. One of the
      antigens implicated in the development of autoimmunity in the prostate is
      prostatic acid phosphatase (PAP), which is also considered a promising target for
      prostate cancer immunotherapy. METHODS: We immunized transgenic (tg) mice
      engineered to express HLA-DRB1*1501 with human PAP. A library of overlapping 20
      mer peptides spanning the entire human PAP sequence was screened in vitro for T
      cell recognition by proliferative and interferon (IFN)-gamma enzyme-linked
      immunosorbent spot (ELISPOT) assays. RESULTS: We identified two 20-mer peptides,
      PAP (133-152), and PAP (173-192), that were immunogenic and naturally processed
      from whole PAP in HLA-DRB1*1501 tg mice. These peptides were also capable of
      stimulating CD4 T lymphocytes from HLA-DRB1*1501-positive patients with GP and
      normal donors. CONCLUSIONS: These peptides can be used for the design of a new
      generation of peptide-based vaccines against prostate cancer. The study can also
      be helpful in understanding the role of autoimmunity in the development of some
      forms of chronic prostatitis.

PMID- 17455232
TI  - Cocaine induces the expression of homer 1b/c, homer 3a/b, and hsp 27 proteins in
      rat cerebellum.
AB  - The long homer proteins 1b/c, 2a/b, and 3a/b play an important role in
      postsynaptic neurons by clustering glutamate receptors and by coupling the
      receptors with various intracellular effectors. Using immunohistochemistry and
      Western-blot analysis, this study shows that the expression of the long homer
      isoforms 1b/c and 3a/b was induced in rat cerebellum in response to cocaine
      administration. Acute treatment produced a very robust induction of both
      constitutive isoforms, whereas repeated treatment for 10 days induced a large
      expression of homer 1b/c and a more modest increase in the expression of the 3a/b
      isoform. The heat shock protein hsp 27 was also considerably induced in the
      cerebellum of cocaine-treated rats, suggesting that it participates in assisting
      the correct folding of proteins, and by counteracting oxidative stress mechanisms
      triggered by the psychostimulant. In addition of being expressed in Purkinje
      neurons, homer 3a/b and hsp 27, but not homer 1b/c, were localized within
      Bergmann glial cells and in their extensions, which surround Purkinje cells, as
      assessed by coimmunoreactivity with glial fibrillary acidic protein. Cocaine was
      also found to induce both proteins in the Bergmann glial cells. Since we found
      that homer 3a/b colocalized with the mGluR1 receptor in Purkinje cells, the data
      suggest that the long homer isoforms are involved in the cocaine-induced
      neuroplasticity that takes place in the cerebellum, by reshaping postsynaptic
      densities in Purkinje cell dendrites.

PMID- 17455233
TI  - Nuclear structure as a source of cancer specific biomarkers.
AB  - There are few biomarkers that have been developed which have proven clinical
      utility for the detection and prognosis of cancer. Cancer is diagnosed today, in
      large part, by examining cells under the microscope and determining the shape and
      texture of the nucleus. The molecular underpinnings of this hallmark of cancer
      are the components of the nuclear matrix. Utilizing proteomics focused on this
      subset of proteins, biomarkers have been identified that are specific for cancer
      types including prostate, colon and bladder cancer. These cancer biomarkers now
      serve as the basis of assays which can specifically identify individuals with
      cancer by sampling their blood and/or urine. In addition, these may serve as
      potential therapeutic targeting or imaging approaches.

PMID- 17455234
TI  - CaMKII can participate in but is not sufficient for the establishment of the
      membrane block to polyspermy in mouse eggs.
AB  - Fertilization triggers initiation of development and establishment of blocks on
      the egg coat and plasma membrane to prevent fertilization by multiple sperm
      (polyspermy). The mechanism(s) by which mammalian eggs establish the membrane
      block to polyspermy is largely unknown. Ca(2+)/calmodulin-dependent protein
      kinase II (CaMKII) appears to be the key regulator of several egg activation
      events (completion of meiosis, progression to embryonic interphase, recruitment
      of maternal mRNAs). Since sperm-induced increases in cytosolic Ca(2+) play a role
      in establishment of the membrane block to polyspermy in mouse eggs, we
      hypothesized that CaMKII was a Ca(2+)-dependent effector leading to this change
      in egg membrane function. To test this hypothesis, we modulated CaMKII activity
      in two ways: activating eggs parthenogenetically by introducing constitutively
      active CaMKIIalpha (CA-CaMKII) into unfertilized eggs, and inhibiting endogenous
      CaMKII in fertilized eggs with myristoylated autocamtide 2-related inhibitory
      peptide (myrAIP). We find that eggs treated with myrAIP establish a less
      effective membrane block to polyspermy than do control eggs, but that CA-CaMKII
      is not sufficient for membrane block establishment, despite the fact that CA
      CaMKII-activated eggs undergo other egg activation events. This suggests that:
      (1) CaMKII activity contributes to the membrane block, but this not faithfully
      mimicked by CA-CaMKII and furthermore, other pathways, in addition to those
      activated by Ca(2+) and CaMKII, also participate in membrane block establishment;
      (2) CA-CaMKII has a range of effects as a parthenogenetic trigger of egg
      activation (high levels of cell cycle resumption, modest levels of cortical
      granule exocytosis, and no membrane block establishment).

PMID- 17455235
TI  - Establishment of vocal communication and discrimination between ewes and their
      lamb in the first two days after parturition.
AB  - In sheep, the mother-young relationship is characterized by an exclusive bond
      that relies on the rapid establishment of mutual recognition. However, the role
      of acoustic cues has been underestimated and neglected in this early
      discrimination. Therefore, the aim of the present study was (1) to characterize
      the vocal behavior of ewes and their lambs during the first 15 days postpartum
      and (2) to investigate the ability of newborn lambs and their mothers to
      discriminate each other from alien subjects within the first 48 hr postpartum on
      the basis of acoustic cues only. Ewes started to vocalize in the last 3 hr
      preceding parturition, emitting mainly high-pitched bleats. However, the bleating
      activity was highest during the first 3 hr following birth, consisting mainly of
      low-pitched bleats. Thereafter it decreased sharply until 24 hr postpartum, with
      most of the activity coming from the mother. In a two-choice test, ewes
      discriminated their own from an alien lamb on the basis of acoustic cues only at
      24 hr postpartum, while lambs did so for their mother at 48 hr, which in both
      cases was much earlier than reported so far. We conclude that early vocal
      recognition between the ewe and her lamb may play an important role for the
      maintenance of mother-young contact.

PMID- 17455236
TI  - Infants' visual-proprioceptive intermodal perception with imperfect contingency
      information.
AB  - Two experiments explored 5-month-old infants' recognition of self-movement in the
      context of imperfect contingencies between felt and seen movement. Previous work
      has shown that infants can discriminate a display of another child's movements
      from an on-line video display of their own movements, even when featural
      information is removed. These earlier findings were extended by demonstrating
      self versus other discrimination when the visual information for movement was an
      unrelated object (a fluorescent mobile) directly attached to the child's leg,
      thus producing imperfect spatial and temporal contingency information. In
      contrast, intermodal recognition failed when the mobile was indirectly attached
      to infants' legs, thus eliminating spatial contingencies altogether and further
      weakening temporal contingencies. Together, these studies reveal that even
      imperfect contingency information can drive intermodal perception, given
      appropriate levels of spatial and temporal contingency information.

PMID- 17455237
TI  - Does muscular weakness account for younger children's enhanced force variability?
AB  - This study examined the degree to which younger children's greater variability in
      force control is associated with muscular weakness. Children aged 6, 8, and 10
      years and adults aged 18-22 years produced isometric force via index finger
      metacarpo-phalangeal joint flexion to varying force levels (5%, 15%, 25%, and 35%
      maximal voluntary contraction). The force output of the younger children was more
      variable and had greater time dependent structure compared to that of the adults
      at all force levels. However, the effect of age on variability was significantly
      reduced, but not eliminated when absolute muscular strength was taken into
      account. It is concluded that age-related changes in children's force control
      result from a multitude of developmental processes including increases in
      muscular strength.

PMID- 17455238
TI  - The molecular mechanisms of vitamin C on cell cycle regulation in B16F10 murine
      melanoma.
AB  - Vitamin C has inconsistent effects on malignant tumor cells, which vary from
      growth stimulation to apoptosis induction. It is well known that melanoma cells
      are more susceptible to vitamin C than any other tumor cells, but the precise
      mechanism remains to be elucidated. In the present study, the proliferation of
      B16F10 melanoma cells was suppressed by vitamin C, which induced growth arrest in
      a dose-dependent manner without cytotoxic effects. Therefore, we investigated the
      changes in cell cycle distribution of B16F10 melanoma cells by staining DNAs with
      propidium iodide (PI). The growth inhibition of B16F10 melanoma by vitamin C was
      associated with an arrest of cell cycle distribution at G1 stage. In addition,
      the levels of p53-p21Waf1/Cip1 increased during G1 arrest, which were essential
      for vitamin C-induced cell cycle arrest. The increased p21Waf1/Cip1 inhibited
      CDK2. Moreover, the activity of p53-p21Waf1/Cip1 pathway was closely related with
      the activation of checkpoint kinase 2 (Chk2). Inhibitor of the PI3K-family,
      LY294002 and the ATM/ATR inhibitor, caffeine, blocked vitamin C-induced growth
      arrest in B16F10 melanoma cells. These results suggest that vitamin C might be a
      potent agent to inhibit proliferative activity of melanoma cells via the
      regulation of Chk2-p53-p21Waf1/Cip1 pathway.

PMID- 17455239
TI  - The influence of training views on infants' long-term memory for simple 3D
      shapes.
AB  - This investigation explored infants' ability to retrieve a memory for a simple 3D
      shape from a novel view following a 24-hr delay. Tests of memory for shape in
      infancy have typically used extremely short delay intervals between
      familiarization and test in examining the ability to equate between substantially
      different views of a 3D object. The current study used longer delays to assess
      the content of a long-term memory representation. Infants 3-4 months of age
      learned to kick to move a mobile displaying a simple 3D shape (brick or
      cylinder). Results of three experiments show that infants can recognize 3D shapes
      in a novel viewpoint across a 24-hr delay, provided that experience with a
      sufficiently wide range of views is available during training. The results
      suggest a capacity for the perception of 3D shape that enables access, across
      long delays, to a memory representation of sufficient detail that discrimination
      between two simple shapes (i.e., a cylinder and a brick) is possible. The results
      suggest that this representation is of a sufficiently abstract nature that
      perception of the 3D form of the object, independent of the changes in specific
      features accompanying changes in viewpoint, is also possible. This finding
      suggests that infants, like adults, possess a functional memory system for the
      distal shape of simple 3D objects, and can transfer training to a novel view
      using long-term memory, but that this ability is not as strong as in the mature
      system. These results have implications for the development of shape perception
      and for theories of object recognition in general.

PMID- 17455240
TI  - Assessment of motor control using kinematics analysis in preschool children born
      very preterm.
AB  - The aim of this study was to better understand the mechanisms underlying the
      motor difficulties encountered by children born very preterm (VPT) without major
      sequelae from preterm birth. We compared the organization of visuo-manual aiming
      in preterm and full term (FT) preschool aged children based on performance and
      kinematics data. Twenty preterm (4 females, 16 males) and 20 sex- and age-matched
      FT children were divided into two age groups (mean age: 3 years-4 months, and 5
      years). Comparison of the performance data showed differences between the older
      preterm and FT children. Kinematics data revealed differences in movement control
      between the younger preterm and FT children. The younger FT children did not
      differ from the older children. In addition, there was an effect of age on both
      performance and kinematics data for the preterm children only. The pattern of
      results suggests difficulties in integrating sensory information for movement
      control in the preterm groups, leading to a delay in the development of visuo
      manual coordination. Kinematics analyses may help identify children at risk for
      poor school performance.

PMID- 17455241
TI  - Fine-tuning of social play in juvenile lowland gorillas (gorilla gorilla
      gorilla).
AB  - Social play, which involves cooperation, communication, and learning, may
      represent a suitable field for the investigation of cognitive ability in a given
      species. We collected data on a captive group of gorillas in order to evaluate
      the potential cognitive skill of juveniles in fine-tuning play behavior. This
      study revealed that juvenile gorillas are able to "place" the play session in a
      proper spatial/temporal context, thus evaluating a complex net of factors (e.g.,
      play partner, play roughness, group activity, space availability). When animals
      play fight, they use patterns of agonistic functional contexts. Since these
      actions are not intrinsically different from their "serious" context, it may be
      hard to distinguish them. One of the most important function of play in the
      ontogeny of primate social cognition may be to recognize stimuli, which may
      indicate the intentions of conspecifics. Accordingly, we found that juvenile
      gorillas are able to use play signals appropriately when a clear statement of
      purpose is necessary (i.e., during male-male competitive play sessions and when
      the escape opportunities are limited). The ability to interpret such ambiguous
      features of social signaling could represent a central issue in the evolution of
      behavioral flexibility and intelligence in primates.

PMID- 17455242
TI  - Gilbert Gottlieb (1929-2006).
AB  - Gilbert Gottlieb, a pioneer in developmental psychobiology, died on July 13,
      2006. We pay tribute to the man, to his career, and to his dedication to
      developmental science.

PMID- 17455243
TI  - Ultrasound, computed tomography, or the combination for the detection of
      supraclavicular lymph nodes in patients with esophageal or gastric cardia cancer:
      a comparative study.
AB  - BACKGROUND AND OBJECTIVES: Both ultrasound (US) and computed tomography (CT) can
      be used to detect supraclavicular lymph node metastases. Aim was to compare US,
      US plus fine-needle aspiration (US-FNA), CT, US + CT, and US-FNA + CT for the
      detection of these metastases in esophageal or gastric cardia cancer patients.
      METHODS: Between 1994 and 2004, 567 patients underwent US and CT for esophageal
      or gastric cardia cancer staging. Gold standard was postoperative detection of
      lymph nodes in the resected specimen, FNA, or a radiological result with follow
      up. RESULTS: Sensitivities of US (75%), US-FNA (72%), US + CT (80%), and US-FNA +
      CT (79%) were higher than sensitivity of CT alone (25%) (P < 0.001).
      Specificities were high for US-FNA (100%), CT (99%), and US-FNA + CT (99%),
      whereas those of US alone (91%) and US + CT (91%) were lower (P < 0.001). In 4/65
      (6%) patients with true-positive malignant lymph nodes, CT was positive with US
      and/or US-FNA being negative. However, in 36/65 (55%) patients, US and/or US-FNA
      were positive with CT being negative. CONCLUSION: US-FNA seems the preferred
      diagnostic modality for the detection of supraclavicular lymph node metastases in
      patients with esophageal or gastric cardia cancer. Sensitivity of metastases
      detection only slightly improves if US-FNA is combined with CT. A prospective,
      comparative study is however needed.

PMID- 17455244
TI  - DNA damage response involves modulation of Ku70 and Rb functions by cyclin A1 in
      leukemia cells.
AB  - Cyclin A1 plays a critical role in hematopoietic malignancies, notably, acute
      myeloid leukemia. The molecular mechanisms of cyclin A1 action are incompletely
      understood. Here, we show that cyclin A1 functions are mediated by the
      retinoblastoma and the Ku70 pathway. High levels of cyclin A1 and the associated
      CDK2 kinase activity were associated with increasing levels of phosphorylated
      retinoblastoma in vivo. UV irradiation induced a switch of the CDK2 towards
      cyclin A1, with accordance to changes in CDK2 kinase activity. The C-terminus of
      cyclin A1 directly interacted with Ku70, and DNA binding activity of Ku70 was
      modulated by cyclin A1/CDK2 and phosphatase treatment. Cyclin A1-deficiency
      induced by shRNA increased apoptosis that is induced by DNA damage and death
      receptor ligands. Taken together, these analyses demonstrate that cyclin A1
      exerts antiapoptotic functions by interacting with retinoblastoma and Ku proteins
      in leukemia cells.

PMID- 17455245
TI  - Salad vegetables dietary pattern protects against HER-2-positive breast cancer: a
      prospective Italian study.
AB  - Studies investigating the relation of diet to breast cancer have produced
      conflicting results. We hypothesized that dietary factors associated with breast
      cancer risk might differentially influence the HER-2 status of the cancers that
      develop, and investigated this hypothesis by analyzing the data of the ORDET
      prospective study. We analyzed 8,861 volunteer women residents of the Varese
      Province, Italy, for whom we had full data. By December 31, 2001, 238 cases had
      occurred in which HER-2 status was known. Four dietary patterns had been
      identified previously by factor analysis: salad vegetables (high consumption of
      raw vegetables and olive oil), prudent (cooked vegetables, poultry, fish),
      western (potatoes, meat, eggs, butter), and canteen (pasta, tomato sauce, wine).
      In our study, relative risks (RRs) of developing HER-2-positive and HER-2
      negative breast cancers by tertiles of dietary pattern factor scores were
      assessed by multinomial logistic regression. The salad vegetables dietary pattern
      had a protective effect against HER-2-positive cancers (RR = 0.25, 95% CI 0.10
      0.64, for the highest tertile; p(trend) = 0.001), much stronger than for HER-2
      negative cancers (p(heterogeneity) = 0.039). This important finding that a salad
      vegetables dietary pattern protects mainly against a specific breast cancer
      subtype indicates that future studies on environmental/dietary risk factors
      should explicitly take account of the heterogeneity of breast cancer phenotypes.

PMID- 17455246
TI  - In vitro and in vivo characterization of [3H]CNS-5161--a use-dependent ligand for
      the N-methyl-D-aspartate receptor in rat brain.
AB  - Glutamate is the major excitatory neurotransmitter in the brain. Glutamate
      activation of the N-methyl-D-aspartate (NMDA) receptor subtype is thought to
      mediate important physiological and pathological processes, including memory
      formation and excitotoxicity. The goal of the present work was to characterize
      and validate a candidate agent for noninvasive positron emission tomography (PET)
      imaging of this receptor. [(3)H]-labeled N-[3-(3)H]-methyl-3
      (thiomethylphenyl)cyanamide (CNS-5161) was incubated with rat brain homogenates
      at increasing concentrations, temperatures, and times to establish the binding
      kinetics and affinity of the ligand in vitro. Nonspecific binding was measured
      with 100 microM MK-801. The compound was also injected i.v. in rats pretreated
      with saline, NMDA, MK801, or a combination, and organ and brain regional uptake
      was assessed at various times after injection by autoradiography or dissection.
      Blood and brain samples were assayed for metabolites by high-performance liquid
      chromatography. CNS-5161 binds brain membranes with high affinity (K(d) < 4 nM)
      and fast association and dissociation kinetics. Specific binding increased in the
      presence of glutamate and glycine. Intravenous administration in control rats
      resulted in a heterogeneous brain distribution with hippocampus and cortex >
      thalamus > striatum > cerebellum, and a cortex/cerebellum ratio of 1.4.
      Pretreatment with NMDA increased the hippocampus-to-cerebellum ratio to 1.6-1.9
      while MK801 abolished this increase, resulting in ratios close to 1. Thus, CNS
      5161 binds preferentially to the activated state of the NMDA receptor channel in
      vitro and in vivo. The high affinity and fast kinetics make it compatible with
      PET imaging of a carbon-11 labeled CNS-5161.

PMID- 17455247
TI  - Kinetic evaluation in nonhuman primates of two new PET ligands for peripheral
      benzodiazepine receptors in brain.
AB  - Peripheral benzodiazepine receptors (PBRs) are upregulated on activated microglia
      and are, thereby, biomarkers of cellular inflammation in brain. We recently
      developed two PET ligands with an aryloxyanilide structure to image PBRs and now
      evaluate the kinetics of these radiotracers in monkey to determine whether they
      are suitable to explore in human. Baseline and receptor-blocking scans were
      performed with [(11)C]PBR01 and [(18)F]PBR06 in conjunction with serial
      measurements of the arterial plasma concentration of parent radiotracer separated
      from radiometabolite. We used brain and plasma data with compartmental modeling
      to calculate regional brain distribution volume, which is equal to the ratio at
      equilibrium of the concentration of radioligand in brain to that of plasma. The
      distribution volume of [(11)C]PBR01 was inaccurately estimated in the baseline
      scans, possibly because of the short half-life of (11)C or the presence of
      radiometabolite in brain. In contrast, the distribution volume of [(18)F]PBR06
      was stably determined within 200 min of scanning, and nondisplaceable uptake was
      only approximately 10% of total brain uptake. [(18)F]PBR06 is promising for use
      in human because brain activity could be quantified with standard compartmental
      models and showed higher ratios ( approximately 10:1) of specific to nonspecific
      uptake. A critical factor for human use will be whether the tracer has adequately
      fast wash out from brain relative to the half-life of the radionuclide to obtain
      stable values of distribution volume.

PMID- 17455248
TI  - Syndecan-1, a key regulator of cell viability in endometrial cancer.
AB  - Syndecan-1 is one of the major proteoglycans on cell surfaces involved in major
      biological processes. Although loss of syndecan-1 correlates well with the gain
      of cancerous characteristics in a wide range of cancers, increased expression of
      syndecan-1 also coincides with adverse outcomes in some cancers, including
      breast, ovarian and pancreatic cancers. For this Janus-faced attitude of syndecan
      1, we sought to examine expression patterns of syndecan-1 in endometrial
      carcinoma (EC) and gain insight into the roles of syndecan-1. Immunohistochemical
      examinations of 109 endometrial tissue samples from myoma, hyperplasia and EC
      uteri revealed that syndecan-1 expression was significantly upregulated in EC
      compared with hyperplasia (p < 0.001). To evaluate pathophysiological functions
      of syndecan-1, its expression level was altered, and subsequent outcomes were
      examined using human endometrial cancer cell lines such as HEC-1A, AN3CA and KLE
      cells. Overexpression of syndecan-1 increased the growth of HEC-1A cells
      regardless of anchorage dependence while silencing syndecan-1 by antisense RNAs
      caused apoptotic cell death. Consistent with decreased viability, the loss of
      syndecan-1 was also accompanied by a decrease in the activation of Erk and Akt
      and a concomitant decrease in the phosphorylation of PTEN and PDK1, which are
      known as negative and positive regulators of Akt activation, respectively. These
      down-regulatory effects were reversed upon overexpression of syndecan-1.
      Collectively together, the aforementioned findings lend support to the notion
      that upregulation of syndecan-1 may be a critical element for endometrial cancers
      in maintaining their viability and thus can serve as a cancer specific
      therapeutic and diagnostic marker.

PMID- 17455249
TI  - Dietary patterns, the Alternate Healthy Eating Index and plasma sex hormone
      concentrations in postmenopausal women.
AB  - To evaluate the association between overall diet and sex hormones concentrations,
      we collected blood from 578 postmenopausal women ages 43 and 69 years in 1989 or
      1990. Food intake was measured in 1990 via a food frequency questionnaire. We
      calculated the Alternate Healthy Eating Index (AHEI), and dietary patterns were
      identified by factor analysis. The cross-sectional association between diet and
      estrogens, sex hormone binding globulin (SHBG) were evaluated with linear
      regression and adjusted for energy and other potential confounders. We found a
      higher AHEI score was associated with lower concentrations of estradiol, free
      estradiol, and higher concentrations of SHBG. The prudent pattern, with higher
      intakes of fruits, vegetables, and whole grains, was not associated with any sex
      hormones. The Western pattern, which represents higher intakes of red and
      processed meats, refined grains, sweets and desserts, was associated with a
      higher level of estradiol and lower concentrations of SHBG. Further adjustment
      for BMI attenuated these results except for free estradiol (5th vs. 1st quintile
      = 0.09 vs. 0.11 pg/mL, p for trend = 0.03). In addition, the AHEI was inversely
      associated with estradiol among those with BMI > 25, and Western pattern with
      SHBG among those with BMI < 25. In conclusion, we observed inverse associations
      between the AHEI score and several estrogens, and it was positively associated
      with plasma levels of SHBG. In contrast, the Western pattern was positively
      associated with estrogen levels and inversely with SHBG. However, these
      associations appeared to be largely accounted for by BMI.

PMID- 17455250
TI  - Colorectal cancer survival in the Nordic countries and the United Kingdom: excess
      mortality risk analysis of 5 year relative period survival in the period 1999 to
      2000.
AB  - A deficit in colorectal cancer survival in Denmark and in the UK compared to
      Sweden, Norway and Finland was found in the EUROCARE studies. We set out to
      explore if these differences still exist. Patients diagnosed with colorectal
      cancer as their first invasive cancer at age 15-89 in the period 1994-2000 were
      identified using data from 11 cancer registries in the UK and from four Nordic
      countries. Five-year relative period survival using deaths in 1999-2000 following
      cancers diagnosed in 1994-2000 was analysed with excess mortality risk modelling.
      Follow-up time since diagnosis with age as an effect-modifier in the first half
      year was the most important factor with the highest excess risk of death
      immediately after diagnosis and with higher age and decreasing with length of
      follow-up. Variations between countries were bigger in the first half year
      following diagnosis than in the interval 0.5-5 years with about 30% higher risk
      in UK and Denmark. The differences between countries are still substantial and
      the order has not changed, even if the five year relative survival has improved
      since the EUROCARE studies. Patient management, diagnostics, and comorbidity
      likely explain the excess deaths in UK and Denmark during the first 6 months. The
      effect of stage and quality of management and treatment should be examined in
      population based studies with detailed patient information. Use of more detailed
      age-intervals than conventionally applied in survival studies proved to be
      important in statistical modelling and is recommended for future studies.

PMID- 17455251
TI  - Obesity does not predispose to more aggressive prostate cancer either at biopsy
      or radical prostatectomy in European men.
AB  - Many investigators suggested that obesity predisposes to adverse prostate cancer
      characteristics and outcomes. We tested the effect of obesity on the rate of
      aggressive prostate cancer at either prostate biopsy or radical prostatectomy
      (RP). Clinical and pathological data were available for 1,814 men. Univariable
      and multivariable logistic regression models addressed the rate of high grade
      prostate cancer (HGPCa) at either biopsy or final pathology. Clinical stage,
      prostate-specific antigen (PSA), percentage of free PSA and prostate volume were
      the base predictors. All models were fitted with and without body mass index
      (BMI), which quantified obesity. BMI and its reciprocal (InvBMI) were coded as
      cubic splines to allow nonlinear effects. Predictive accuracy (PA) was quantified
      with area under curve estimates, which were subjected to 200 bootstrap re-samples
      to reduce overfit bias. Gains in PA related to the inclusion of BMI were compared
      using the Mantel-Haenszel test. HGPCa at biopsy was detected in 562 (31%) and
      HGPCa at RP pathology was present in 931 (51.3%) men. In either univariable or
      multivariable models predicting HGPCa at biopsy, BMI or InvBMI failed to
      respectively reach statistical significance or add to multivariable PA (BMI gain
      = 0%, p = 1.0; InvBMI gain = -0.2%, p = 0.9). Conversely, in models predicting
      HGPCa at RP, BMI and InvBMI represented independent predictors but failed to
      increase PA (BMI gain = 0.7%, p = 0.6; InvBMI gain = 0.5, p = 0.7%). Obesity does
      not predispose to more aggressive prostate cancer at biopsy. Similarly, obesity
      does not change the ability to identify those who may harbor HGPCa at RP.

PMID- 17455252
TI  - Global expression profiling of murine MEN1-associated tumors reveals a regulatory
      role for menin in transcription, cell cycle and chromatin remodelling.
AB  - Although the identification of menin-interacting partners and other evidence
      support a role for menin, the multiple endocrine neoplasia type 1 gene (MEN1)
      product, in regulating gene expression, little is known about the cellular
      pathways dysregulated by menin loss during tumorigenesis. The mouse models of
      MEN1 accurately mimic the human syndrome and provide an opportunity to assess the
      transcriptional effects of Men1 deletion in different endocrine tumor types to
      identify common pathway aberrations underlying tumorigenesis in MEN1-affected
      tissues. We compared the global gene expression profiles of pituitary adenomas
      and pancreatic islet tumors with control tissues from wild-type littermates.
      Amongst the 551 differentially expressed genes was significant over
      representation of genes associated with chromatin remodelling, transcription and
      cell cycling, including some genes known to encode menin-binding partners, e.g.,
      Rhox5 and Mll1. Consistent with increased cell-cycle transition from G1 to S
      phase was an elevation of Cdc7 expression in the tumors, which was confirmed by
      qRT-PCR using independent samples. In support of previous findings in islet
      tumors, we found down-regulation of the cell-cycle regulator, p18, in both the
      pancreatic islet and pituitary adenomas, suggesting that reduced p18 levels may
      be important for Men1-related tumorigenesis in multiple tissues. Surprisingly, we
      identified increased p16 transcript in pancreatic islet and pituitary tumors.
      This was accompanied by increased cytoplasmic localization p16 protein in tumor
      cells. The specific genes and general pathways we have found to be commonly
      dysregulated in MEN1 tumors, provide a platform for determining their roles in
      endocrine tumorigenesis.

PMID- 17455255
TI  - Recurrent disruption of the Imu splice donor site in t(14;18) positive lymphomas:
      a potential molecular basis for aberrant downstream class switch recombination.
AB  - t(14;18) positive lymphomas are mature germinal center B-cell neoplasms. In
      agreement with this cellular origin, most have somatically mutated immunoglobulin
      variable genes and the IGH@ locus has almost always been reorganized by class
      switch recombination (CSR). However, contrasting with normal B-cells, a majority
      of cases still express an IgM while the constant genes are normally rearranged
      only on the non-productive allele. Concurrently, aberrant intra-allelic junctions
      involving downstream switch regions, with a lack of engagement of the switch mu
      (Smu), often accumulate on the functional alleles, suggesting some recurrent CSR
      perturbation during the onset of the disease. To clarify these surprising
      observations, we addressed the accessibility of the Smu to the CSR machinery in a
      large series of patients by characterizing the mutations that are expected to
      accumulate at this place upon CSR activation. Our data indicate that the Smu is
      mutated in a large majority of cases, often on both alleles, indicating that
      these cells usually reach a differentiation stage where CSR is activated and
      where this region remains accessible. Interestingly, we also identified a
      significant cluster of mutations at the splicing donor site of the first exon of
      the Smu germline transcripts, on the functional allele. This location suggests a
      possible relation with CSR perturbations in lymphoma and the clustering points to
      a probable mechanism of selection. In conclusion, our data suggest that an
      acquired mutation at the splicing donor site of the Smu transcripts may
      participate in the selection of lymphoma cells and play a significant role during
      the onset of the disease.

PMID- 17455256
TI  - Prognostic significance of matrix metalloproteinases-1, -2, -7 and -13 and tissue
      inhibitors of metalloproteinases-1, -2, -3 and -4 in colorectal cancer.
AB  - Strong expression of many matrix metalloproteinases (MMPs) has been related to
      poor survival of colorectal cancer (CRC) patients. The expression of tissue
      inhibitors of metalloproteinases (TIMPs) has been associated with both a
      beneficial and a poor outcome and there is thus a need to further clarify the
      significance of MMPs and TIMPs in CRC. The prognostic significance of 4 MMPs and
      TIMPs in CRC was evaluated. Formalin-fixed, paraffin-embedded tissue arrayed
      samples of 351 patients with primary colon or rectal cancer of Dukes' stages A-D
      were selected for immunohistochemical staining of MMP-1, -2, -7 and -13, and TIMP
      1, -2, -3 and -4. High expression of MMP-2 in the malignant epithelium as well as
      in the surrounding stroma was associated with reduced survival of colon cancer
      patients. Strong epithelial and stromal cytoplasmic staining of TIMP-3 was
      associated with a longer survival in rectal cancer patients, and here the
      interobserver variation for evaluating the degree of staining was lower than for
      epithelial staining. Strong stromal cytoplasmic staining of TIMP-4 predicted
      longer survival of rectal cancer patients. Multivariate analysis showed that
      stromal cytoplasmic TIMP-3 staining was the only marker of independent prognostic
      value. MMP-2 might be a useful prognostic marker in colon cancer, and TIMP-3 and
      TIMP-4 in rectal cancer, but the findings associated with stromal staining should
      be interpreted with some caution. Different biologic behavior or different
      genetic development may explain the differences between colon and rectal cancers
      regarding the expression of MMP-2, TIMP-3 and TIMP-4.

PMID- 17455257
TI  - Co-twin control and cohort analyses of body mass index and height in relation to
      breast, prostate, ovarian, corpus uteri, colon and rectal cancer among Swedish
      and Finnish twins.
AB  - Associations between anthropometric measures and cancer have been studied
      previously, but relatively few studies have had the opportunity to control for
      genetic and early shared environmental factors. In this study, we analyzed 2 twin
      cohorts from Sweden born 1886-1925 (n = 21,870) and 1926-1958 (n = 30,279) and 1
      from Finland born 1880-1958 (n = 25,882) including in total 78,031 twins, and
      studied the association between BMI and height and risk of prostate, breast,
      ovarian, corpus uteri, colon and rectal cancer. The cohorts were both analyzed
      through a co-twin control method and as traditional cohorts. In co-twin control
      analyses, older obese (BMI > or = 30 kg/m(2)) subjects (median age 56 years at
      baseline) were at higher risk of cancer of the corpus uteri (OR = 3.0; 95% CI 0.9
      10.6), colon (OR = 1.9; 95% CI 0.8-4.5) and breast (OR = 2.5; 95% CI 1.3-4.2).
      For younger obese women (median age 30 years at baseline), an inverse tendency
      was observed for breast cancer (OR = 0.6; 95% CI 0.3-1.5, p for trend = 0.05).
      The tallest women had an increased risk of breast (OR = 1.8; 95% CI 1.3-2.7) and
      ovarian cancer (OR = 1.7; 95% CI 0.8-3.5). No consistent associations were found
      for prostate cancer either for BMI or height. There are some suggestions in our
      study that uncontrolled genetic or early shared environmental factors may affect
      risk estimates in studies of anthropometric measures and cancer risk, but do not
      explain observations of increased cancer risks related to BMI or height.

PMID- 17455258
TI  - Induction of Smad1 by MT1-MMP contributes to tumor growth.
AB  - MT1-MMP is a key integral membrane protease, which regulates tumor growth by
      cleaving extracellular matrix components, activating growth factors and
      receptors, and consequently, triggering downstream signals. To study what genes
      or pathways are mediated by endogenous MT1-MMP during tumor growth in vivo, we
      stably suppressed endogenous MT1-MMP in human tumor cells using RNA interference
      (RNAi). Tumor growth was significantly reduced in tumors derived from MT1-MMP
      suppressed cells relative to control cells; the effect was rescued in cells
      engineered to re-express MT1-MMP expression. Gene expression profiling of
      cultured and tumor-derived cells by DNA microarray and real-time RT-PCR revealed
      that Smad1 expression was upregulated in MT1-MMP-expressing cells and rapidly
      growing tumors; this was confirmed in 4 additional tumor cell lines. Furthermore,
      tumor growth of MT1-MMP-expressing cells was reduced when Smad1 was suppressed by
      RNAi. We also found that the active form, but not the latent form, of TGF-beta
      was capable in promoting Smad1 expression and 3D cell proliferation in MT1-MMP
      suppressed cells. In addition, a dominant-negative form of the TGF-beta Type II
      receptor reduced Smad1 expression in MT1-MMP-expressing cells. Thus, we propose
      that MT1-MMP functions, in part, to promote tumor growth by inducing the
      expression of Smad1 via TGF-beta signaling.

PMID- 17455259
TI  - Distinct pharmacological properties of second generation HDAC inhibitors with the
      benzamide or hydroxamate head group.
AB  - Advanced second generation inhibitors of histone deacetylases (HDAC) are
      currently used in clinical development. This study aimed at comparing the
      pharmacological properties of selected second generation HDAC inhibitors with the
      hydroxamate and benzamide head group, namely SAHA, LAQ824/LBH589, CI994, MS275
      and MGCD0103. In biochemical assays using recombinant HDAC1, 3, 6 and 8
      isoenzymes, SAHA and LAQ824/LBH589 behave as quite unselective HDAC inhibitors.
      In contrast, the benzamides CI994, MS275 and MGCD0103 are more selective, potent
      inhibitors of at least HDAC1 and HDAC3. All HDAC inhibitors induce histone H3
      hyperacetylation, correlating with inhibition of proliferation, induction of cell
      differentiation and apoptosis. A broad cytotoxicity is seen across cell lines
      from different tumor entities with LAQ824/LBH589 being the most potent agents.
      The apoptosis inducing activity is evident in arrested and proliferating RKO
      colon cancer cells with inducible, heterologous p21(waf1) expression, indicative
      for a cell-cycle independent mode-of-action. Differentiation of MDA-MB468 breast
      cancer cells is induced by benzamide and hydroxamate analogs. The reversibility
      of drug action was evaluated by pulse treatment of A549 lung cancer cells.
      Whereas paclitaxel induced irreversible cell cycle alterations already after 6 hr
      treatment, HDAC inhibitor action was retarded and irreversible after >16 hr
      treatment. Interestingly, pulse treatment was equally effective as continous
      treatment. Finally, the efficacy of LAQ824, SAHA and MS275 in A549 nude mice
      xenografts was comparable to that of paclitaxel at well tolerated doses. We
      conclude that despite a different HDAC isoenzyme inhibition profile, hydroxamate
      and benzamide analogs as studied display similar cellular profiles.

PMID- 17455261
TI  - Application of atomic force microscopy on observing the ultra-fine structure of
      the neoproterozoic microfossils from China.
AB  - Phosphatic microfossils from the Doushantuo Formation, Guizhou, China, have been
      reported with preserved cellular structure or even sub-cellular structure in
      micron scale. However, more details in sub-micro scale have not been reported as
      having been found. The Fossil embryos from the acid residue of the phosphorite
      rocks of the Neoproterozoic Doushantuo Formation in south China have been studied
      with a scanning electron microscope (SEM) and an atomic force microscope (AFM).
      Some ultra-structures in sub-micro scale have been found by AFM on the surface of
      the fossil embryos. There are four types of structures found on the surface of
      the selected fossil embryos, the sizes of which vary from 30 to 645 nm in
      diameter under our AFM. One of the structures is composed of several big sub
      units integrated with each other, and the size of the big sub-units is from 250
      to 645 nm. Meanwhile, we also found an ultra-layer structure on the surface of
      the big sub-units, the thickness of which was about 10 nm. Thus we speculate that
      it could most probably be of biological origin. Therefore, AFM provides a new
      method for direct observation of the ultra-structure of the Doushantuo fossils in
      the sub-micro scale.

PMID- 17455262
TI  - Skirting: a limitation for the performance of X-ray microanalysis in the variable
      pressure or environmental scanning electron microscope.
AB  - The variable pressure or environmental scanning electron microscope (VP-SEM;
      ESEM) has become the microscope of choice for many scientists and technologists.
      Hence, the development of robust methods for X-ray microanalysis, limited by
      skirting, has become critical. In this paper, two pressure variation correction
      methods (Doehne and Gauvin) are compared. Both of these methods appear to be
      effective; the results were found to be well within 10% of the values obtained at
      0 Pa. The Doehne method is dependent on an empirical factor (D), therefore the
      accuracy of the results will depend on the accuracy of this value. Also the
      Doehne method is compromised by the nonlinearity of the response with pressure.
      The Gauvin method is more user-friendly and more precise when considering the
      total range of pressure.

PMID- 17455263
TI  - Imaging of silkworm meiotic chromosome by atomic force microscopy.
AB  - Although structural information of mitotic chromosomes has been accumulated,
      little information is available for meiotic chromosome structures. Here, we
      applied atomic force microscopy (AFM) to investigate the ultrastructures of the
      silkworm, Bombyx mori, meiotic pachytene chromosome in its native state with
      nanometer scale resolution. Two levels of DNA folding were observed on the
      meiotic chromosome surface, 50-70 nm granules, which were considered to be 30 nm
      chromatin fibers, and spherical protrusions of 400-600 nm, which were considered
      to be chromomeres and arranged on the surface of the chromosome parallel to the
      chromosome longitudinal axis. These observations suggested that AFM study is an
      excellent approach for obtaining information concerning the silkworm pachytene
      chromosome higher order structure.

PMID- 17455264
TI  - Motor unit number estimates and quantitative motor unit analysis in healthy
      subjects and patients with amyotrophic lateral sclerosis.
AB  - Limitations associated with global measures of function in patients with
      amyotrophic lateral sclerosis (ALS) and the qualitative nature of needle
      electromyography have stimulated the development of alternate means of monitoring
      disease severity and progression in ALS. Thus, the objective of this study was to
      examine the ability of one these techniques, decomposition-based quantitative
      electromyography (DQEMG), to obtain electrophysiological data, including motor
      unit number estimates (MUNEs), from a group of patients with ALS. The first
      dorsal interosseous and biceps brachii muscles were studied in 10 healthy
      subjects and 9 patients with ALS. Following the acquisition of a maximum M wave,
      needle- and surface-detected EMGs were collected simultaneously during 30-second
      contractions performed at 10% of the maximum voluntary contraction force to
      obtain motor unit potential (MUP) trains. DQEMG was then used to extract the
      surface-detected MUP associated with each MUP train, the mean size of which was
      divided into the maximum M wave to obtain a MUNE. The results suggest that
      quantitative electrophysiological data obtained using DQEMG are representative of
      the pathophysiological changes in the lower motor system in ALS patients,
      supporting its use in studies documenting the natural history and progression of
      the disease.

PMID- 17455265
TI  - Inflammatory pseudotumor of the peroneal nerve.

PMID- 17455266
TI  - Contribution of reference electrode to the compound muscle action potential.
AB  - In compound muscle action potential (CMAP) recording, the contribution by the
      reference electrode is considered to be much smaller than that of the active
      electrode. We tested this assumption by making quantitative measurements of the
      signals recorded individually by the active and reference electrodes. In the
      thenar (median nerve) and extensor digitorum brevis (peroneal nerve) muscles, the
      reference electrode did contribute less. In the hypothenar muscle (ulnar nerve),
      however, the signals recorded by active and reference electrodes were of similar
      amplitude. In tibial nerve conduction studies (NCS), the CMAP from the abductor
      hallucis (AH) muscle was recorded mainly by the reference electrode; the large
      amplitude signal recorded by the reference electrode is attributed to volume
      conducted activity from other muscles stimulated during the study. The onset
      latency of the potential recorded by the active and reference electrodes was
      similar despite significantly different distances from the stimulating site.
      Hence, the merits of using anatomic landmarks for defining the distal stimulation
      site are assessed. When the reference electrode makes a large contribution, the
      CMAP amplitude may not decrease commensurate with any wasting of the muscle under
      the active recording electrode, and the need to use another muscle for recording
      the CMAP for that nerve should be considered.

PMID- 17455267
TI  - Strontium-substituted apatite coating grown on Ti6Al4V substrate through
      biomimetic synthesis.
AB  - During the last few years Strontium has been shown to have beneficial effects
      when incorporated at certain doses in bone by stimulating bone formation. It is
      believed that its presence locally at the interface between an implant and bone
      will enhance osteointegration and therefore, ensure the longevity of a joint
      prosthesis. In this study we explore the possibility of incorporating Sr into
      nano-apatite coatings prepared by a solution-derived process according to an
      established biomimetic methodology for coating titanium based implants. The way
      this element is incorporated in the apatite structure and its effects on the
      stereochemistry and morphology of the resulting apatite layers was investigated,
      as well as its effect in the mineralization kinetics. By using the present
      methodology it was possible to incorporate increasing amounts of Sr in the
      apatite layers. Sr was found to incorporate in the apatite layer through a
      substitution mechanism by replacing Ca in the apatite lattice. The presence of Sr
      in solution induced an inhibitory effect on mineralization, leading to a decrease
      in the thickness of the mineral layers. The obtained Sr-substituted biomimetic
      coatings presented a bone-like structure similar to the one found in the human
      bone and therefore, are expected to enhance bone formation and osteointegration.

PMID- 17455268
TI  - Sol gel derived SiO(2)-CaO-MgO-P(2)O(5) bioglass system--preparation and in vitro
      characterization.
AB  - The synthesis of SiO(2)-CaO-MgO-P(2)O(5) bioactive glass was carried out by the
      sol-gel method. Sol-gel derived bioglass material was crushed into powder to
      produce pellet disks by uniaxial pressing, followed by sintering at 900 degrees
      C. The biocompatibility evaluation of the formed glass was assessed through in
      vitro cell culture experiments and immersion studies in simulated body fluid
      (SBF) for different time intervals while monitoring the pH changes and the
      concentration of calcium and magnesium in the SBF medium. Scanning electron
      microscopy, X-ray energy dispersive spectroscopy, X-ray diffraction analysis, and
      FT-IR spectroscopy studies were conducted before and after contact of the
      material with SBF. At first, an amorphous calcium phosphate was formed; after 21
      days this surface consisted of deposited crystalline spheres of apatite. The
      present investigation also revealed that the sol-gel derived quaternary bioglass
      system has the ability to support the growth of osteoblast-like cells in vitro
      and to promote osteoblast differentiation by stimulating the expression of major
      phenotypic markers.

PMID- 17455269
TI  - Surface micro-analyses of long-term worn retrieved "Osteal" alumina ceramic total
      hip replacement.
AB  - We analyzed wear pattern of long-term retrieved alumina-alumina hip prostheses
      from Osteal, which were implanted for 15-19 years. A comparison was carried out
      with our previous study of 17-year Biolox alumina-on-alumina hip prostheses,
      (Shishido et al., J Biomed Mater Res B 2003;67:638-647) and all-alumina total hip
      replacement run under microseparation simulator tests. Of particular interest was
      the occurrence of stripe wear in these first generation alumina ceramic bearings.
      Two balls of Osteal revealed only one stripe wear as did the respective liners on
      their rim areas. In these latter balls, the stripes were shallower than those
      previously observed in Biolox implants. A microscopic analysis of the bearing
      surface was carried out using scanning electron microscopy and fluorescence
      microprobe spectroscopy. On average, the Osteal retrievals had one grade lower
      wear than Biolox retrievals. Fluorescence microprobe maps showed that Biolox ball
      surfaces had higher compressive stress than the Osteal likely due to severe
      impingement and microseparation promoted by the bulky implant design.

PMID- 17455270
TI  - Growth of osteoblast-like cells on biomimetic apatite-coated chitosan scaffolds.
AB  - Porous scaffold materials that can provide a framework for the cells to adhere,
      proliferate, and create extracellular matrix are considered to be suitable
      materials for bone regeneration. Interconnected porous chitosan scaffolds were
      prepared by freeze-drying method, and were mineralized by calcium and phosphate
      solution by double-diffusion method to form nanoapatite in chitosan matrix. The
      mineralized chitosan scaffold contains hydroxyapatite nanocrystals on the surface
      and also within the pore channels of the scaffold. To assess the effect of
      apatite and porosity of the scaffolds on cells, human osteoblast (SaOS-2) cells
      were cultured on unmineralized and mineralized chitosan scaffolds. The cell
      growth on the mineralized scaffolds and on the pure chitosan scaffold shows a
      similar growth trend. The total protein content and alkaline phosphatase enzyme
      activity of the cells grown on scaffolds were quantified, and were found to
      increase over time in mineralized scaffold after 1 and 3 weeks of culture. The
      electron microscopy of the cell-seeded scaffolds showed that most of the outer
      macropores became sealed off by a continuous layer of cells. The cells spanned
      around the pore wall and formed extra cellular matrix, consisting mainly of
      collagen in mineralized scaffolds. The hydroxyproline content also confirmed the
      formation of the collagen matrix by cells in mineralized scaffolds. This study
      demonstrated that the presence of apatite nanocrystals in chitosan scaffolds does
      not significantly influence the growth of cells, but does induce the formation of
      extracellular matrix and therefore has the potential to serve for bone tissue
      engineering.

PMID- 17455271
TI  - Monomer conversion and cytotoxicity of dental composites irradiated with
      different modes of photoactivated curing.
AB  - The aim of the study was to compare the monomer conversion and cytotoxicity of
      two resin composites, Tetric Ceram (TC) and Heliomolar (HM), irradiated with a
      halogen light-curing unit (Optilux 501) using a number of curing modes, boost
      (OB), ramp (OR), and conventional (OC), as well as a light-emitting diode (LED)
      curing unit (LEDemetron; LEDe). The effects of irradiation times (10, 20, 30, and
      40 s) were also investigated. The monomer conversion of resin composites was
      measured using Fourier transform infrared (FTIR) analysis. Resin samples were
      preimmersed in Dulbeco's modified engles medium (DMEM) for 24 h, and the
      periodontal ligament cells (PDL) were cultured with aged medium for 72 h to
      evaluate the cytotoxic effects of resin samples using the microtiter-tetrazolium
      (MTT) method. The spectral outputs of the curing units were also compared. After
      irradiation using the same curing mode, the TC monomer conversion was higher than
      the HM analog. The TC conversion value was lower after OC and LEDemetron
      irradiation for 10 s compared to exposures of 30 and 40 s. The HM conversion
      value was lowest for the 10-s OC irradiation, and highest for the 40-s OC
      exposure. In cytotoxicity tests, the negative control group was without
      irradiation. The succinate dehydrogenase (SDH) activities of the OB and OR
      irradiated TC samples were significantly lower than analogs irradiated with
      LEDemetron for 40 s; however, no significant differences were demonstrated
      between OB, OR, and control groups. Further, no significant differences in SDH
      activity were demonstrated for OB, OR, and control groups of the HM.

PMID- 17455272
TI  - Morphology and ultrastructure of differentiating three-dimensional mammalian
      skeletal muscle in a collagen gel.
AB  - Because previous studies of three-dimensional skeletal muscle cultures have shown
      limited differentiation, the goal of this study was to establish conditions that
      would produce mature sarcomeres in a mammalian-derived skeletal muscle construct.
      We evaluated the differentiation of bioartificial muscles generated from
      C(2)C(12) myoblasts in a collagen gel cultured under steady, passive tension for
      up to 36 days. Staining for alpha-actinin, myosin, and F-actin indicated the
      presence of striated fibers as early as 6 days post-differentiation. Electron
      microscopy at 16 days post-differentiation revealed multinucleated myotubes with
      ordered, striated myofibers. At 33 days, the cultures contained collagen fibers
      and showed localization of paxillin at the fiber termini, suggesting that
      myotendinous junctions were forming. The present study demonstrates mature muscle
      synthesis in a three-dimensional system using a pure mammalian myoblast cell
      line. Our results suggest that this culture model can be used to evaluate the
      effects of various mechanical and biochemical cues on muscle development under
      normal and pathological conditions.

PMID- 17455273
TI  - The prevalence and risk factors of urinary incontinence and its influence on the
      quality of life among Egyptian women.
AB  - AIMS: The exact magnitude of the problem of urinary incontinence (UI) in Egypt is
      not yet reported. We studied the prevalence and potential risk factors associated
      with UI among a group of Egyptian women as taken from a representative sample
      from the population. METHODS:  DESIGN: A cross-sectional, community-based study.
      SETTING: Assiut, Upper Egypt, Egypt. PARTICIPANTS: women, aged 20 years and
      older, selected randomly from the population. MEASUREMENTS: PARTICIPANTS
      completed a previously validated questionnaire; Urogenital Distress Inventory
      short form (UDI-6). RESULTS: A total of 1,652 women were included. The prevalence
      of UI among our study subjects is 54.8%. Aging, low educational level, menopause,
      higher parity (>3), vaginal delivery, and previous multiple abortions (>3) were
      found to be significantly associated with UI. The prevalence of urge, stress and
      mixed incontinence, mutually exclusive of each other, was 15%, 14.8%, and 25%,
      respectively. The prevalence of severe incontinence is 8.4%. Regarding the
      quality of life, the most distressing issues for sufferers were their inability
      to pray (90%). CONCLUSIONS: UI is quite common in Egypt and prevalence rates are
      higher when compared to other reports.

PMID- 17455274
TI  - Bladder dysfunction in type 2 diabetic patients.
AB  - AIMS: To reevaluate urodynamic findings of bladder dysfunction (BD) in type 2
      diabetic patients with patient characteristics and concommittant chronic
      complications. METHODS: Patients (M/F:27/27) with lower urinary tract symptoms
      (LUTS) underwent a detailed urodynamic investigation. Urodynamic findings were
      classified as diabetic cystopathy [DC, characterized by impaired bladder
      sensation, increased post-void residual urine (PVR) and increased bladder
      capacity and decreased bladder contractility], detrusor overactivity, bladder
      outlet obstruction (BOO), urge and stress urinary incontinence or BD in which one
      of the alterations was included. Glycated hemoglobin (HbA1C), diabetic
      retinopathy, nephropathy, sensorimotor, and autonomic neuropathies were
      evaluated. RESULTS: BD was present in 74.07% of men (DC, 50%; BOO, 25%; detrusor
      overactivity, 25%) and in 59.26% of diabetic women (DC, 43.75%; detrusor
      overactivity, 31%; urge incontinence, 12.5%; stress urinary incontinence 12.5%).
      In men, age, duration of diabetes and HbA1C threshold values predicting BD were
      >64 years, >9 year, >7.9%, while in women, they were >56 years, >8 years, >7%,
      respectively. Prolongation of QTc, abnormal esophageal transit and gastric
      emptying times, diabetic retinopathy, and microalbuminuria were associated with
      an increased risk of PVR >or= 100 ml. CONCLUSIONS: DC was the most frequent
      finding in patients. Ageing, duration of diabetes, worse metabolic control, PVR
      100 ml, cardiac, esophageal and gastric parasympathetic autonomic neuropathies,
      retinopathy, and microalbuminuria provided a means to predict BD in patients in
      order to investigate by urodynamics. The establishment of DC in at least 8-9
      years after the diagnosis of type 2 DM was an important parameter to inform our
      diabetic patients.

PMID- 17455275
TI  - Protective effects of antioxidants on micronuclei induced by irradiated 9
      fluorenone/N,N-dimethyl-p-toluidine in CHO cells.
AB  - 9-Fluorenone (9F), the aromatic photosensitizer, is widely used as an initiator
      in visible-light (VL) cured resin systems. There is growing concern that 9F may
      produce genetic damage by inducing mutation. In this study, 9F in the presence or
      absence of reducing agent N,N-dimethyl-p-toluidine (DMT) with or without VL
      irradiation was analyzed for the induction of chromosomal aberrations indicated
      by micronuclei (MN) induced in CHO cells. Our data demonstrated that a dose
      related increase in the frequency of MN and prolonged cell cycles in 9F with or
      without DMT in the presence or absence of VL irradiation (p < 0.05). The rank
      orders with respect to genotoxicity and cytotoxicity were found to be as follows:
      9F/DMT +VL > 9F/DMT = 9F + VL > 9F. To determine whether oxidative stress could
      modulate MN induced by 9F/DMT with or without VL irradiation in CHO cells, cells
      were pretreated with N-acetyl-L-cysteine (NAC), ascorbic acid, and alpha
      tocopherol. The pretreatment with antioxidants could diminish not only the
      prolonged cell cycle but also the decreased frequency of MN which is induced by
      9F with or without DMT in the presence or absence of VL irradiation in CHO cells
      (p < 0.05). Our findings provide the evidences for the induction of MN by 9F in
      the presence or absence of DMT with or without VL irradiation in CHO cells,
      indicating clastogenic activity of 9F/DMT in vitro. These antioxidants act as the
      antagonists against the genotoxicity and cytotoxicity of 9F/DMT. Thus, leaching
      photoinitiator and reducing agent might be contributing the sources of oxidative
      stress.

PMID- 17455276
TI  - Evaluation of novel injectable hydrogels for nucleus pulposus replacement.
AB  - Branched copolymers composed of poly(N-isopropylacrylamide) (PNIPAAm) and
      poly(ethylene glycol) (PEG) are being investigated as an in situ forming
      replacement for the nucleus pulposus of the intervertebral disc. A family of
      copolymers was synthesized by varying the molecular weight of the PEG blocks and
      molar ratio of NIPAAm monomer units to PEG branches. Gel swelling, dissolution,
      and compressive mechanical properties were characterized over 90 days and stress
      relaxation behavior over 30 days immersion in vitro. It was found that the NIPAAm
      to PEG molar ratio did not affect the equilibrium swelling and compressive
      mechanical properties. However, gel elasticity exhibited a dependency on both the
      PEG block molecular weight and content. The equilibrium gel water content
      increased and compressive modulus decreased with increasing PEG block size. While
      all of the branched copolymers showed significant increases in stress relaxation
      time constant compared to the homopolymer (p < 0.05), the high PEG content
      PNIPAAm-PEG (4600 and 8000 g/mol) exhibited the maximum elasticity. Because of
      its high water content, requisite stiffness and high elastic response, PNIPAAm
      PEG (4600 g/mol) will be further evaluated as a candidate material for nucleus
      pulposus replacement.

PMID- 17455277
TI  - Mechanical basis for bone retention around dental implants.
AB  - This study, analytically, through finite element analysis, predicts the
      minimization of crestal bone stress resulting from implant collar surface
      treatment. A tapered dental implant design with (LL) and without (control, C)
      laser microgrooving surface treatment are evaluated. The LL implant has the same
      tapered body design and thread surface treatment as the C implant, but has a 2-mm
      wide collar that has been laser micromachined with 8 and 12 microm grooves in the
      lower 1.5 mm to enhance tissue attachment. In vivo animal and human studies
      previously demonstrated decreased crestal bone loss with the LL implant. Axial
      and side loading with two different collar/bone interfaces (nonbonded and bonded,
      to simulate the C and LL surfaces, respectively) are considered. For 80 N side
      load, the maximum crestal bone distortional stress around C is 91.9 MPa, while
      the maximum crestal bone stress around LL, 22.6 MPa, is significantly lower.
      Finite element analysis suggests that stress overload may be responsible for the
      loss of crestal bone. Attaching bone to the collar with LL is predicted to
      diminish this effect, benefiting crestal bone retention.

PMID- 17455278
TI  - Surface patterning: tool to modulate stem cell differentiation in an adipose
      system.
AB  - There are several issues that need to be better understood before breast tissue
      engineering becomes viable clinically. One of the key issues is the interaction
      between cells and the microtopography of the implant surface. The aim of this
      study was to evaluate the efficacy of D1 cells, multipotent mouse bone marrow
      stromal precursors, in differentiating to fat and to characterize their metabolic
      activity (lactic acid released and glucose consumed) and lipid production when
      cultured on patterned poly-L-lactide (PLLA) films. It was determined that, with
      appropriate stimulation, the D1 cells displayed morphological characteristics of
      adipocytes and produced lipid. The results show that the patterned surfaces did
      affect the rate of lipid production. Polynomial models were proposed to predict
      the metabolic activity of the cells over a period of time.

PMID- 17455279
TI  - Fabrication of novel calcium phosphate/poly(lactic acid) fiber composites.
AB  - Composites using high-modulus polylactic acid (PLA) fibers coated with calcium
      phosphate (CaP) were prepared using a cyclic precipitation technique. Scanning
      electron microscopy revealed that small nuclei of CaP formed after the first
      soaking cycle, while large quantities of CaP particles were observed after the
      sixth cycle. The amount of CaP deposited on the PLA yarn increased with
      deposition time in Ca(2+) and PO(4) (3-) solutions and number of cycles, and
      decreased with stirring rate during washing cycles. It was observed that around
      35 wt % of CaP was deposited on the yarn surface after six cycles of cyclic
      soaking. Based on the results, a heterogeneous nucleation and growth mechanism
      was proposed for the CaP deposition on the surface of hydrolyzed polyester.
      Composites comprising the coated fibers in a poly(caprolactone) matrix exhibited
      flexural moduli within the range of that of the cortical bone.

PMID- 17455280
TI  - The effect of roughness on the tribological behavior of the prosthetic pair
      UHMWPE/TiN-coated stainless steel.
AB  - The effect of roughness on the tribological behavior of the prosthetic pair ultra
      high molecular weight polyethylene (UHMWPE)/TiN coated stainless steel was
      investigated. Standard and polished TiN coated stainless steel pins were tested
      against either standard or smooth UHMWPE disks. Hanks' Balanced Salt Solution
      (HBSS) and bovine serum albumin (BSA) solution in HBSS were used as lubricants.
      Friction and wear were determined using a pin-on-disk apparatus and the wear
      mechanisms were investigated through optical microscopy, scanning electron
      microscopy, and atomic force microscopy. The results showed that the decrease in
      the roughness led to a reduction of the friction coefficient and of the wear rate
      of UHMWPE. However, the most important effect was achieved through the decrease
      in the roughness of the hard TiN counterface while keeping the standard UHMWPE
      surface. If BSA was added to HBSS, a strong decrease of both the friction
      coefficient and the polymeric wear was observed independently of the roughness of
      both the TiN and the polyethylene surfaces. Abrasive and fatigue wear mechanisms
      are proposed to interpret the experimental results.

PMID- 17455281
TI  - Effect of water storage time and composite cement thickness on fatigue of a glass
      ceramic trilayer system.
AB  - AIM: Static Hertzian contact tests of monolayer glass-ceramics in trilayer
      configurations (glass-ceramic/cement/composite) have shown that thick cement
      layers lower strength. This study sought to test the hypothesis that thick resin
      cement layers lower mouth motion fatigue reliability for flat glass
      ceramic/cement/composite trilayer systems and that aging in water reduces
      reliability. METHODS: Dicor plates (n > or = 12 per group) (10 x 10 x 0.8 mm(3))
      were aluminum-oxide abraded (50 microm), etched (60 s), silanized, and bonded
      (Rely X ARC) to water aged (30 days) Z100 resin blocks (10 x 10 x 4 mm(3)). Four
      groups were prepared: (1) thick cement layer (>100 microm) stored in water for 24
      48 h, (2) thick cement layer stored for 60 days, (3) thin cement layer (< or =100
      microm) stored for 24-48 h, and (4) thin cement layer stored for 60 days. The
      layered structures were fatigued (2 Hz) utilizing mouth motion loading with a
      step-stress acceleration method. A master Weibull distribution was calculated and
      reliability determined (with 90% confidence intervals) at a given number of
      cycles and load. RESULTS: The aged group (60 d) with thick cement layer had
      statistically lower reliability for 20,000 cycles at 150 N peak load (0.11)
      compared with both nonaged groups (24-48 h) (thin layer = 0.90 and thick layer =
      0.82) and aged group with thin cement layer (0.89). CONCLUSION: Trilayer
      specimens with thick cement layers exhibited significantly lower reliability
      under fatigue testing only when stored for 60 days in water. The hypothesis was
      accepted. These results suggest that diffusion of water into the resin cement and
      also to the glass-ceramic interface is delayed in the thick cement specimens at
      24-48 h. .

PMID- 17455282
TI  - Thermoreversible gel-sol behavior of biodegradable PCL-PEG-PCL triblock copolymer
      in aqueous solutions.
AB  - A series of biodegradable PCL-PEG-PCL block copolymers were successfully
      synthesized by ring-opening polymerization of epsilon-caprolactone initiated by
      poly(ethylene glycol) (PEG), which were characterized by (1)H NMR, (13)C NMR, and
      FTIR. Their aqueous solution displayed special gel-sol transition behavior with
      temperature increasing from 4 to 100 degrees C, when the polymer concentration
      was above corresponding critical gel concentration (CGC). The gel-sol phase
      diagram was recorded using test tube inverting method and DSC method, which
      depended not only on chemical composition of copolymers, but also on heating
      history of copolymer's aqueous solution. As a result, the gel-sol transition
      temperature could be adjusted, which might be very useful for its application in
      biomedical fields such as injectable drug delivery system. And the typical shell
      core structure of PCL-PEG-PCL micelles was introduced. The micelle-packing and
      partial crystallization might be the key gelation machanism for this gel-sol
      transition behavior of PCL-PEG-PCL aqueous solution.

PMID- 17455283
TI  - CASINO V2.42: a fast and easy-to-use modeling tool for scanning electron
      microscopy and microanalysis users.
AB  - Monte Carlo simulations have been widely used by microscopists for the last few
      decades. In the beginning it was a tedious and slow process, requiring a high
      level of computer skills from users and long computational times. Recent progress
      in the microelectronics industry now provides researchers with affordable desktop
      computers with clock rates greater than 3 GHz. With this type of computing power
      routinely available, Monte Carlo simulation is no longer an exclusive or long
      (overnight) process. The aim of this paper is to present a new user-friendly
      simulation program based on the earlier CASINO Monte Carlo program. The intent of
      this software is to assist scanning electron microscope users in interpretation
      of imaging and microanalysis and also with more advanced procedures including
      electron-beam lithography. This version uses a new architecture that provides
      results twice as quickly. This program is freely available to the scientific
      community and can be downloaded from the website: (www.gel.usherb.ca/casino).

PMID- 17455284
TI  - Intraspecific variation in hair delta(13)C and delta(15)N values of ring-tailed
      lemurs (Lemur catta) with known individual histories, behavior, and feeding
      ecology.
AB  - Stable carbon and nitrogen isotope compositions were analyzed from hair samples
      of 30 sympatric ring-tailed lemurs (Lemur catta) inhabiting the Beza Mahafaly
      Special Reserve, Madagascar. All lemurs were known individuals involved in a
      longitudinal study, which allowed us to explore the degree to which group
      membership, sex, health status, and migration influenced their stable isotope
      compositions. The differences in delta(13)C and delta(15)N values between groups
      were small (<1.5 per thousand) but highly significant. In fact, each group was
      tightly clustered, and discriminant function analysis of the stable isotope data
      assigned individuals to the group in which they were originally collared with
      over 90% accuracy. In general, the differences between groups reflected the
      degree to which they utilized forested versus open habitats. As open habitats at
      Beza Mahafaly often correspond to areas of anthropogenic disturbance, these data
      suggest that isotopic data can be useful for addressing questions of lemur
      conservation. There were few sex differences, but significant differences did
      occur between individuals of normal and suboptimal health, with those in poor
      health (especially those in the worst condition) being enriched in (15)N and to a
      lesser degree (13)C compared with healthy individuals. Moreover, lemurs that had
      emigrated between 2003 and 2004 had different delta(13)C and delta(15)N
      compositions than their original groups.

PMID- 17455285
TI  - Rethinking incisor size and diet in anthropoids: diet, incisor wear and incisor
      breadth in the African apes.
AB  - In a seminal study Hylander (1975) concluded that the length of the incisor row
      in catarrhines considered frugivores is longer relative to body mass than in
      those classified as folivores. Assuming that large fruits require greater incisal
      processing than do leaves, stems, berries, and seeds, he argued that the larger
      incisors of frugivores increased their resistance to wear. The present analysis
      examines diet, incisor wear, and incisor crown breadth in cranial samples of
      western lowland gorillas and chimpanzees. Incisor wear rate was assessed on the
      basis of the extent of incisor crown reduction observed at sequential stages of
      first molar wear. Incisor metrics were obtained from the unworn teeth of
      juveniles. Results suggest that incisor wear is greater in the more folivorous
      western lowland gorillas than in more frugivorous chimpanzees. Moreover, incisor
      crown dimensions do not differ appreciably among African apes. These findings
      fail to support the hypothesis that slower wear rates are associated with broader
      incisor crowns, and raise new questions regarding the significance of incisor row
      length in anthropoids.

PMID- 17455286
TI  - Origins and spread of agriculture in Italy: a nonmetric dental analysis.
AB  - Dental morphological traits were employed in this study as direct indicators of
      biological affinities among the populations that inhabited the Italian peninsula
      from the Upper Paleolithic-Mesolithic to Medieval times. Our analysis aims at
      contributing to the ongoing debate regarding the origin and spread of agriculture
      in the peninsula by contrasting the dental evidence of archaeological and modern
      molecular samples. It is not possible to generalize given the complex and dynamic
      nature of these populations. However, the results from the principal component
      analysis, maximum likelihood, mean measure of divergence, and multidimensional
      scaling do indicate a net separation of the Paleo-Mesolithic sample from the
      other groups that is not related to dental reduction. This suggests that the
      shift in dental morphology was the product of Neolithic populations migrating
      into the peninsula from other areas. Nonetheless, the Paleo-Mesolithic
      populations share several discriminative traits with the Neolithic group. The
      biological relevance of such evidence suggests that, to some minor extent, the
      spread of agriculture did not occur by total population replacement. Because of
      regional small sample sizes, this hypothesis cannot be tested on a micro-regional
      scale. It is, however, feasible to depict a scenario where processes of genetic
      mixture or replacement probably took place at different rates on a macro-regional
      level.

PMID- 17455288
TI  - The synapsin cycle: a view from the synaptic endocytic zone.
AB  - Although the synapsin phosphoproteins were discovered more than 30 years ago and
      are known to play important roles in neurotransmitter release and synaptogenesis,
      a complete picture of their functions within the nerve terminal is lacking. It
      has been shown that these proteins play an important role in the clustering of
      synaptic vesicles (SVs) at active zones and function as modulators of synaptic
      strength by acting at both pre- and postdocking levels. Recent studies have
      demonstrated that synapsins migrate to the endocytic zone of central synapses
      during neurotransmitter release, which suggests that there are additional
      functions for these proteins in SV recycling.

PMID- 17455289
TI  - Mutation of a potassium channel-related gene in progressive myoclonic epilepsy.
AB  - OBJECTIVE: We investigated a large consanguineous Moroccan family with
      progressive myoclonic epilepsy (PME) consistent with autosomal recessive
      inheritance, to describe the phenotype and identify the causal gene. METHODS: We
      recorded the clinical course of the disease and the response to drug therapy,
      whereas carefully excluding known causes of progressive myoclonic epilepsy. We
      then linked the disease by homozygosity mapping using microsatellite markers and
      single nucleotide polymorphism microarrays (11K GeneChip), and studied candidate
      genes in the critical linkage region. RESULTS: Epilepsy started between 16 and 24
      months of age after normal initial development. Seizures were multifocal
      myoclonus aggravated by movements, and generalized tonic-clonic seizures were
      experienced by two patients. Electroencephalogram showed slow dysrhythmia,
      multifocal and occasionally generalized epileptiform discharges, and
      photosensitivity. Brain magnetic resonance images were normal. All patients were
      demented. Two had refractory epilepsy and a severe course. Seizures were
      controlled in the third patient, whose disease course was less severe. Linkage
      analyses identified a new locus on 7q11.2, with a maximum multipoint logarithm of
      odds of 4.0 at D7S663. In the critical linkage region, we found a C to T mutation
      in exon 2 of the potassium channel tetramerization domain containing 7 gene
      (KCTD7). The mutation affected a highly conserved segment of the predicted
      protein, changing an arginine codon into a stop codon (R99X). INTERPRETATION:
      Neurodegeneration in progressive myoclonic epilepsy presented by our patients
      paralleled the refractoriness of epilepsy. The disease was transmitted as an
      autosomal recessive trait linked to a novel locus at 7q11.2, where we identified
      a mutation in KCTD7.

PMID- 17455290
TI  - Electrophysiological characterization of neural stem/progenitor cells during in
      vitro differentiation: study with an immortalized neuroectodermal cell line.
AB  - Despite the accumulating data on the molecular and cell biological
      characteristics of neural stem/progenitor cells, their electrophysiological
      properties are not well understood. In the present work, changes in the membrane
      properties and current profiles were investigated in the course of in vitro
      induced neuron formation in NE-4C cells. Induction by retinoic acid resulted in
      neuronal differentiation of about 50% of cells. Voltage-dependent Na+ currents
      appeared early in neuronal commitment, often preceding any morphological changes.
      A-type K+ currents were detected only at the stage of network formation by
      neuronal processes. Flat, epithelial- like, nestin-expressing progenitors
      persisted beside differentiated neurons and astrocytes. Stem/progenitor cells
      were gap junction coupled and displayed large, symmetrical, voltage-independent
      currents. By the blocking of gap junction communication, voltage-independent
      conductance was significantly reduced, and delayed-rectifying K+ currents became
      detectable. Our data indicate that voltage-independent symmetrical currents and
      gap junction coupling are characteristic physiological features of neural stem
      and progenitor cells regardless of the developmental state of their cellular
      environment.

PMID- 17455291
TI  - A specific viral cause of multiple sclerosis: one virus, one disease.
AB  - "Multiple sclerosis is an autoimmune disease," is heard so often that it is
      widely accepted as fact by the current generation of students and physicians.
      Yet, although it is undisputed that multiple sclerosis (MS) is immune mediated,
      an autoimmune mechanism remains unproven. Immune-mediated tissue damage can also
      result from viral infections in which the host immune response is directed to
      viral rather than self proteins, or as a consequence of nonspecific or bystander
      immune responses that change the local cytokine environment. Increasing evidence
      suggests that poorly controlled host immune responses account for much of the
      tissue damage in chronic infections, and it has been postulated that a similar
      mechanism may underlie many chronic diseases with features suggestive of an
      infectious causative factor, including MS. A recent study suggesting that
      oligodendrocyte death accompanied by microglial activation is the primary event
      in new MS lesion formation, rather than lymphocyte infiltration, could change the
      current mindset almost exclusively focused on autoimmunity. This review presents
      the rationale for considering MS a single disease caused by one virus, as well as
      the anticipated pattern of a persistent central nervous system infection, the
      application of Koch's postulates to viral discovery in MS as the causative agent,
      and tissue culture-independent genotypic approaches to viral discovery in MS.

PMID- 17455292
TI  - Muscle Nogo-A expression is a prognostic marker in lower motor neuron syndromes.
AB  - OBJECTIVE: A proportion of patients with pure lower motor neuron syndrome (LMNS)
      progress to amyotrophic lateral sclerosis (ALS). Early detection of this
      progression is impossible, which delays the patient's access to treatment. Muscle
      expression of Nogo-A is a new candidate marker of ALS. We tested whether
      detection of Nogo-A in a muscle biopsy from patients with LMNS predicts
      progression to ALS. METHODS: Thirty-three patients who had undergone a muscle
      biopsy during the diagnostic workup of spinal LMNS were observed for 12 months.
      Nogo-A expression was measured by Western blot in muscle biopsy samples and
      compared with the final diagnosis. RESULTS: Nogo-A expression was detected in 17
      patients and was absent in 16 patients. The detection of Nogo-A in muscle biopsy
      samples from LMNS patients correctly identified patients who further progressed
      to ALS with 91% accuracy, 94% sensitivity, and 88% specificity. In patients who
      later developed typical ALS, Nogo-A may be detected as early as 3 months after
      the onset of symptoms. INTERPRETATION: Nogo-A test is able to identify ALS early
      in the course of the disease when diagnosis is difficult, requiring further
      progression. Use of the test in clinical practice may shorten the delay before
      introduction of neuroprotective drugs or inclusion in clinical trials.

PMID- 17455293
TI  - Effects of motor and sensory nerve transplants on amount and specificity of
      sciatic nerve regeneration.
AB  - Nerve regeneration after complete transection does not allow for adequate
      functional recovery mainly because of lack of selectivity of target
      reinnervation. We assessed if transplanting a nerve segment from either motor or
      sensory origin may improve specifically the accuracy of sensory and motor
      reinnervation. For this purpose, the rat sciatic nerve was transected and
      repaired with a silicone guide containing a predegenerated segment of ventral
      root (VR) or dorsal root (DR), compared to a silicone guide filled with saline.
      Nerve regeneration and reinnervation was assessed during 3 months by
      electrophysiologic and functional tests, and by nerve morphology and
      immunohistochemistry against choline acetyltransferase (ChAT) for labeling motor
      axons. Functional tests showed that reinnervation was successful in all the rats.
      However, the two groups with a root allotransplant reached higher degrees of
      reinnervation in comparison with the control group. Group VR showed the highest
      reinnervation of muscle targets, whereas Group DR had higher levels of sensory
      reinnervation than VR and saline groups. The total number of regenerated
      myelinated fibers was similar in the three groups, but the number of ChAT+ fibers
      was slightly lower in the VR group in comparison with DR and saline groups. These
      results indicate that a predegenerated root nerve allotransplant enhances axonal
      regeneration, leading to faster and higher levels of functional recovery.
      Although there is not clear preferential reinnervation, regeneration of motor
      axons is promoted at early times by a motor graft, whereas reinnervation of
      sensory pathways is increased by a sensory graft.

PMID- 17455294
TI  - Ubiquitin-proteasome system alterations in a striatal cell model of Huntington's
      disease.
AB  - Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative
      disease caused by an abnormally expanded CAG repeat in the HD gene. Ubiquitylated
      aggregates containing mutant huntingtin protein in neurons are hallmarks of HD.
      Misfolded mutant huntingtin monomers, oligomers, or aggregates may be a result
      of, and cause, ubiquitin- proteasome dysfunction. To investigate the ubiquitin
      proteasome system we designed a series of firefly luciferase reporters targeted
      selectively to different points along this pathway. These reporters were used to
      monitor ubiquitin-proteasome system function in a striatal cell culture model of
      HD. Ubiquitylation processes were not reduced in mutant huntingtin cells but
      recognition or degradation of ubiquitylated substrates was decreased. We also
      found mutant huntingtin expressing cells had slight but significant decreases in
      chymotrypsin-like and caspase-like activities, and an unexpected increase in
      trypsin-like activity of the proteasome core. General proteasome core inhibitors,
      as well as selective caspase-like activity inhibitors, were less effective in
      mutant cells. Finally, treatment with 3-nitropropionic acid, a succinate
      dehydrogenase inhibitor, had opposite effects on the ubiquitin-proteasome system
      with activation in wild-type and decreased activity in mutant huntingtin
      expressing cells. The results of these experiments show clearly selective
      disruption of the ubiquitin-proteasome system in this cell culture model of HD.
      The high throughput tools that we have designed and optimized will also be useful
      in identifying compounds that alter ubiquitin-proteasome system function and to
      investigate other neurodegenerative diseases such Alzheimer's disease and
      Parkinson's disease.

PMID- 17455295
TI  - Additional clinical manifestations in children with sensorineural hearing loss
      and biallelic GJB2 mutations: who should be offered GJB2 testing?
AB  - Sensorineural hearing loss (SNHL), the most common sensory impairment noted at
      birth, occurs in 3 out of every 1,000 births live births. At least half of
      congenital SNHL is genetic in origin, with nonsyndromic, or isolated hearing
      loss, accounting for approximately 70% of the total genetic causes. Syndromic
      hearing loss (hearing loss associated with other clinical findings) makes up the
      remaining 30%. Worldwide, mutations in the gap junction beta 2 (GJB2) gene,
      encoding the connexin 26 (Cx26) protein, are responsible for approximately 30% of
      all cases of childhood SNHL. GJB2 mutations have been primarily associated with
      nonsyndromic forms of bilateral SNHL although rare syndromic forms involving
      dermatologic manifestations have also been reported. In general, unless skin
      findings are present, children with bilateral SNHL and other structural or
      developmental abnormalities are not generally thought of as candidates for GJB2
      testing. We evaluated 163 individuals with biallelic GJB2 mutations and SNHL for
      the presence of other clinical findings. Twenty-nine of the 163 (18%) were found
      to have structural and/or developmental abnormalities in addition to the SNHL and
      four subjects had diagnoses that were felt to account for their hearing loss
      prior to being screened for GJB2 mutations. Although the GJB2 mutations are
      likely not responsible for these additional clinical manifestations, this study
      underscores the importance of considering GJB2 mutational analysis in individuals
      with more than just isolated SNHL given the high prevalence of GJB2-related
      hearing loss.

PMID- 17455297
TI  - Bioenergetics of mitochondria in cultured neurons and their role in glutamate
      excitotoxicity.
AB  - The pathologic activation of NMDA receptors by glutamate is a major contributor
      to neuronal cell death after stroke. Receptor activation causes a massive influx
      of calcium into the neuron that is accumulated by the mitochondria. The favored
      hypothesis is that the calcium loaded mitochondria generate reactive oxygen
      species that damage and ultimately killed the neuron. In this review this
      hypothesis is critically re-examined with an emphasis on the role played by
      deficits in ATP generation. Novel techniques are developed to monitor the
      bioenergetic status of in situ mitochondria in cultured neurons. Applying these
      techniques to a model of glutamate excitotoxicity suggests that enhanced reactive
      oxygen species are a consequence rather than a cause of failed cytoplasmic
      calcium homeostasis (delayed calcium deregulation, [DCD]), but that prior
      oxidative damage facilitates DCD by damaging mitochondrial ATP generation. This
      impacts on current hypotheses relating to the neuroprotective effects of mild
      mitochondrial uncoupling.

PMID- 17455296
TI  - Expression of insulin-like growth factor system genes during the early postnatal
      neurogenesis in the mouse hippocampus.
AB  - Insulin-like growth factor-1 (IGF-1) is essential to hippocampal neurogenesis and
      the neuronal response to hypoxia/ischemia injury. IGF (IGF-1 and -2) signaling is
      mediated primarily by the type 1 IGF receptor (IGF-1R) and modulated by six high
      affinity binding proteins (IGFBP) and the type 2 IGF receptor (IGF-2R),
      collectively termed IGF system proteins. Defining the precise cells that express
      each is essential to understanding their roles. With the exception of IGFBP-1, we
      found that mouse hippocampus expresses mRNA for each of these proteins during the
      first 2 weeks of postnatal life. Compared to postnatal day 14 (P14), mRNA
      abundance at P5 was higher for IGF-1, IGFBP-2, -3, and -5 (by 71%, 108%, 100%,
      and 98%, respectively), lower for IGF-2, IGF-2R, and IGFBP-6 (by 65%, 78%, and
      44%, respectively), and unchanged for IGF-1R and IGFBP-4. Using laser capture
      microdissection (LCM), we found that granule neurons and pyramidal neurons
      exhibited identical patterns of expression of IGF-1, IGF-1R, IGF-2R, IGFBP-2, and
      -4, but did not express other IGF system genes. We then compared IGF system
      expression in mature granule neurons and their progenitors. Progenitors exhibited
      higher mRNA levels of IGF-1 and IGF-1R (by 130% and 86%, respectively), lower
      levels of IGF-2R (by 72%), and similar levels of IGFBP-4. Our data support a role
      for IGF in hippocampal neurogenesis and provide evidence that IGF actions are
      regulated within a defined in vivo milieu.

PMID- 17455298
TI  - Characterization of the rat urokinase plasminogen activator receptor promoter in
      PC12 cells.
AB  - Rat PC12 pheochromocytoma cells treated with nerve growth factor (NGF) extend
      "neurites" and initiate a neuronal differentiation pathway. Although
      neurotrophins, growth factors [e.g., epidermal growth factor (EGF)], and other
      ligands induce many common primary response genes (PRGs) in PC12 cells, a unique
      PRG subset is induced preferentially by NGF. Expression of one NGF preferentially
      induced gene, urokinase plasminogen activator receptor (UPAR), is required for
      NGF-induced neurite extension and neuronal differentiation. A 2.1-kb fragment of
      the rat UPAR 5' regulatory region confers differential expression by NGF versus
      EGF, following transfection of a luciferase reporter construct into PC12 cells.
      Deletion studies identified a region between -100 and -50 nucleotides from the
      transcription start site as the region conferring preferential NGF induction.
      Sequence comparisons among rat, human, and murine UPAR promoters identified two
      common potential regulatory regions. Site-directed mutation identified an
      activator protein-1 (AP-1) region between -66 and -72 bp, required for luciferase
      reporter activation by NGF. Electrophoretic mobility shift and antibody
      supershift assays demonstrated that specific Fos and Jun family members
      preferentially bind to this site following NGF treatment. We conclude that
      preferential activation of transcription factor binding at this AP-1 site
      mediates preferential NGF activation of the UPAR gene.

PMID- 17455299
TI  - c-Jun phosphorylation in Alzheimer disease.
AB  - The c-Jun N-terminal kinase (JNK) pathway is known to be activated by oxidative
      stress and can lead to either defensive-protective adaptations in the cell or
      apoptosis. The JNK pathway is activated in Alzheimer disease (AD), as
      demonstrated in studies showing higher levels of phospho-JNK in affected neurons
      in AD brains than in controls. c-Jun, a transcription factor, is the downstream
      effector of JNK, whose activation requires phosphorylation of Ser63/Ser73. In
      this study, we characterized and compared the localization of c-Jun
      phosphorylated at either Ser63 or Ser73 in the hippocampi of AD cases with that
      in age-matched controls. Phospho-c-Jun (Ser73) was found to be strongly
      associated with neurofibrillary tangles and granulovacuolar degeneration (GVD) in
      addition to the nuclei in neurons in the hippocampal regions of the AD brain, but
      was virtually absent in most controls. Phospho-c-Jun (Ser63) was also found to be
      associated with GVD in AD brains. Indeed, phospho-c-Jun (Ser73) immunostaining
      was much more extensive than that of phospho-c-Jun (Ser63), with all the phospho
      c-Jun (Ser63)-positive neurons also being phospho-c-Jun (Ser73) positive.
      Significant overlap between phospho-c-Jun and phospho-JNK suggested a mechanistic
      link. In addition, the neurons showing increased levels of phospho-c-Jun (Ser73)
      in the cytoplasmic GVD were negative for TUNEL, suggesting a mechanism protecting
      the cells from death. Overall, this study demonstrated specific alterations in c
      Jun phosphorylation and distribution in AD which is not necessarily linked to
      apoptosis but rather may represent an adaptation process in the face of oxidative
      stress.

PMID- 17455300
TI  - Identification of phase boundaries in anhydrate/hydrate systems.
AB  - Near-infrared spectroscopy was used to monitor the phase conversion for two
      solvatomorphs of caffeine, an anhydrous form and a nonstoichiometric hydrate, as
      a function of time, temperature, and relative humidity. The transformation
      kinetics between these caffeine forms was determined to increase with
      temperature. The rate of conversion was also determined to be dependent on the
      difference between the observed relative humidity and the equilibrium water
      activity of the anhydrate/hydrate system, that is, phase boundary. Near the phase
      boundary, minimal conversion between the anhydrous and hydrated forms of caffeine
      was detected. Using this kinetic data, the phase boundary for these forms was
      determined to be approximately 67% RH at 10 degrees C, 74.5% RH at 25 degrees C,
      and 86% RH at 40 degrees C. At each specified temperature, anhydrous caffeine is
      the thermodynamically stable form below this relative humidity and the hydrate is
      stable above. The phase boundary data were then fitted using a second order
      polynomial to determine the stability relationship between anhydrous caffeine and
      its hydrate at additional temperatures. This approach can be used to rapidly
      determine the stability relationship for solvatomorphs as well as the relative
      kinetics of their interconversion. Both of these factors are critical in
      selecting the development form, designing appropriate stability studies, and
      developing robust conditions for the preparation and packaging of the API and
      formulated drug product.

PMID- 17455301
TI  - Expression of zinc finger transcription factor Bcl11A/Evi9/CTIP1 in rat brain.
AB  - Bcl11A/Evi9/CTIP1, a Kruppel-like zinc finger gene, plays an important role in B
      cell development. In addition to expression in B lymphocytes, Bcl11A/Evi9/CTIP1
      is also highly expressed in the brain, although its function there is still
      unclear. In the present study, regional and subcellular distributions of
      Bcl11A/Evi9/CTIP1 in rat brain were investigated by immunostaining and
      biochemical fractionation. Using antibodies recognizing the first 18 amino acid
      residues of Bcl11A/Evi9/CTIP1, the distribution of 2 isoforms of
      Bcl11A/Evi9/CTIP1 gene products, Bcl11A-L/Evi9a and Bcl11A-S/Evi9c, was examined.
      In rat brain, both Bcl11A-L/Evi9a and Bcl11A-S/Evi9c were expressed, although the
      amount of Bcl11A-S/Evi9c protein was higher. Bcl11A-S/Evi9c was widely expressed
      in different regions of the rat brain. In contrast, Bcl11A-L/Evi9a was more
      restricted, being expressed in the cerebral cortex, hippocampus, and olfactory
      bulb. At the subcellular level, biochemical fractionation and confocal analysis
      of adult rat brain revealed that, in addition to being in the nuclei of neurons,
      fractions of Bcl11A-L/Evi9a and Bcl11A-S/Evi9c could be found in extranuclear
      locations. Double staining with the synaptic marker synaptophysin indicated a
      synaptic distribution of Bcl11A/Evi9/CTIP1. Postsynaptic density was also
      biochemically purified and subjected to immunoblotting using Bcl11A/Evi9/CTIP1
      antibodies. The results showed that Bcl11A-L/Evi9a was enriched in the PSD I and
      PSD II fractions. In contrast, only a trace amount of Bcl11A-S was detected in
      PSD fractions. Our study also indicated that a fraction of Bcl11A/Evi9/CTIP1 was
      present in the cytoplasm, even at synapses. To regulate gene expression in the
      nuclei, nuclear translocation of Bcl11A/Evi9/CTIP1 may be one of the mechanisms
      controlling neuronal Bcl11A/Evi9/CTIP1 function.

PMID- 17455302
TI  - Metabolic interactions between glutamatergic and dopaminergic neurotransmitter
      systems are mediated through D(1) dopamine receptors.
AB  - Interactions between the dopaminergic and glutamatergic neurotransmission systems
      were investigated in the adult brain of wild-type (WT) and transgenic mice
      lacking the dopamine D(1) or D(2) receptor subtypes. Activity of the glutamine
      cycle was evaluated by using (13)C NMR spectroscopy, and striatal activity was
      assessed by c-Fos expression and motor coordination. Brain extracts from (1,2
      (13)C(2)) acetate-infused mice were prepared and analyzed by (13)C NMR to
      determine the incorporation of the label into the C4 and C5 carbons of glutamate
      and glutamine. D(1)R(-/-) mice showed a significantly higher concentration of
      cerebral (4,5-(13)C(2)) glutamine, consistent with an increased activity of the
      glutamate-glutamine cycle and of glutamatergic neurotransmission. Conversely,
      D(2)R(-/-) mice did not show any significant changes in (4,5-(13)C(2)) glutamate
      or (4,5-(13)C(2)) glutamine, suggesting that alterations in glutamine metabolism
      are mediated through D(1) receptors. This was confirmed with D(1)R(-/-) and WT
      mice treated with reserpine, a dopamine-depleting drug, or with reserpine
      followed by L-DOPA, a dopamine precursor. Exposure to reserpine increased (4,5
      (13)C(2)) glutamine in WT to levels similar to those found in untreated D(1)R(-/
      ) mice. These values were the same as those reached in the reserpine-treated
      D(1)R(-/-) mice. Treatment of WT animals with L-DOPA returned (4,5-(13)C(2))
      glutamine levels to normal, but this was not verified in D(1)R(-/-) animals.
      Reserpine impaired motor coordination and decreased c-Fos expression, whereas L
      DOPA restored both variables to normal values in WT but not in D(1)R(-/-).
      Together, our results reveal novel neurometabolic interactions between
      glutamatergic and dopaminergic systems that are mediated through the D(1), but
      not the D(2), dopamine receptor subtype.

PMID- 17455303
TI  - Prediction of the onset of crystallization of amorphous sucrose below the
      calorimetric glass transition temperature from correlations with mobility.
AB  - The objective of the present work is to determine if crystallization onset
      observed for an amorphous solid correlate with relaxation time at temperatures
      above and below the calorimetric glass transition (T(g)). Crystallization onset
      of spray-dried and freeze-dried amorphous sucrose were measured calorimetrically.
      Relaxation times measured in two temperature ranges by different techniques
      (isothermal calorimetry, dielectric spectroscopy) followed the expected modified
      Vogel-Tammann-Fulcher (VTF) behavior when extrapolated to a temperature near
      T(g). However, the change in slope was more conspicuous for freeze-dried sucrose,
      indicating that amorphous materials generated using different techniques differ
      in their mobilities for temperatures below T(g). Dielectric relaxation time
      values obtained above T(g) were well correlated to onset of crystallization. The
      model predicted 21 days for crystallization onset for spray-dried samples stored
      7 K below T(g), compared to the experimentally observed crystallization onset of
      17 days. Onset times versus temperature for freeze-dried sucrose, however, show a
      change in slope on approaching T(g), with the onsets somewhat decoupling from
      measured mobility for temperatures below T(g). Molecular mobility in amorphous
      materials at temperatures both above and below T(g) can be correlated to
      macroscopic physical change such as crystallization, but prediction of
      crystallization onset from relaxation time is only qualitatively correct at
      temperatures well below T(g).

PMID- 17455304
TI  - Activation of endogenous neural stem cells in the adult human brain following
      subarachnoid hemorrhage.
AB  - In the adult human brain, the presence of neural stem cells has been documented
      in the subgranular layer of the dentate gyrus of the hippocampus and in the
      subventricular zone of the lateral ventricles. Neurogenesis has also been
      reported in rodent models of ischemic stroke, traumatic brain injury, epileptic
      seizures, and intracerebral or subarachnoid hemorrhage. However, only sparse
      information is available about the occurrence of neurogenesis in the human brain
      under similar pathological conditions. In the present report, we describe neural
      progenitor cell proliferation in the brain of patients suffering from
      subarachnoid hemorrhage (SAH) resulting from ruptured aneurysm. Ten cerebral
      samples from both SAH and control patients obtained, respectively, during
      aneurysm clipping and deep brain tumor removal were analyzed by reverse
      transcription followed by polymerase chain reaction (RT-PCR) and/or
      immunohistochemistry (IHC). In tissue specimens from SAH patients, RT-PCR and IHC
      revealed the expression of a variety of markers consistent with CNS progenitor
      cells, including nestin, vimentin, SOX-2, and Musashi1 and -2. In the same
      specimens, double immunohistochemistry followed by confocal analysis revealed
      that Musashi2 consistently colocalized with the proliferation marker Ki67. By
      contrast, no such gene or protein expression profiles were detected in any of the
      control specimens. Thus, activation of neural progenitor cell proliferation may
      occur in adult human brain following subarachnoid hemorrhage, possibly
      contributing to the promotion of spontaneous recovery, in this pathological
      condition.

PMID- 17455305
TI  - Glycogen is a preferred glutamate precursor during learning in 1-day-old chick:
      biochemical and behavioral evidence.
AB  - Bead discrimination training in chicks sets in motion a tightly timed series of
      biochemical events, including glutamate release, increase in forebrain level of
      glutamate and utilization of glycogen and glucose. Inhibition of glycogen
      breakdown by the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D
      arabinitol (DAB) around the time of training abolishes the increase in glutamate
      5 min posttraining in the left hemisphere, in spite of uninhibited glucose
      metabolism. It also reduces the contents of glutamate, glutamine, and aspartate
      in the right hemisphere. Behavioral evidence supports the conclusion that glucose
      breakdown serves to provide energy, whereas glycogen acts as a substrate for
      glutamate, glutamine, and aspartate formation, requiring both pyruvate
      dehydrogenation to acetyl coenzyme A and pyruvate carboxylation in astrocytes.
      Inhibition of memory consolidation caused by DAB or 2-deoxyglucose (2-DG), an
      inhibitor of glucose phosphorylation without effect on glycogen metabolism, was
      challenged by intracerebral administration of acetate, aspartate, glutamine,
      lactate or glucose. DAB-mediated memory inhibition was successfully challenged by
      administration at 0 or 20 min posttraining of acetate (an astrocyte-specific
      acetyl CoA precursor) together with aspartate, substituting for pyruvate
      carboxylation, or of glutamine at 0-2.5 or 30 min posttraining. 2-DG-mediated
      memory impairment was not challenged by acetate with or without aspartate at 0
      time but was challenged by acetate without aspartate at 20 min. Lactate, a
      substrate for both dehydrogenation and pyruvate carboxylation challenged both DAB
      and 2-DG. Doses of DAB and 2-DG which, on their own were subeffective, were not
      additive, further supporting the existence of one pathway using glucose and
      another using glycogen.

PMID- 17455306
TI  - Endoplasmic reticulum-associated degradation of the NR1 but not the NR2 subunits
      of the N-methyl-D-aspartate receptor induced by inhibition of the N-glycosylation
      in cortical neurons.
AB  - The N-methyl-D-aspartate receptor (NMDAR) is fundamental to normal and
      pathological functioning of neurons. The receptor subunits are N-glycosylated
      proteins synthesized in the endoplasmic reticulum (ER) that fold, mature, and
      oligomerize as they transit through the secretory pathway. Although the early
      processes of biogenesis are fundamental to NMDAR expression and function, our
      knowledge of them is nevertheless limited. Additionally, the investigation of
      NMDAR synthesis is highly relevant, in that ER dysfunction, frequently associated
      with acute and degenerative brain diseases, might alter this process. We
      characterize here the effect of ER stress produced by inhibition of N
      glycosylation on NMDAR synthesis and function. We use first heterologous systems
      of NMDAR expression in which NR1 and NR2A subunits are synthesized in nonneuronal
      cells. The function of these NMDARs as Ca2+ channels is repressed by tunicamycin,
      because of the inhibition of NR1, but no NR2A, synthesis. The regulation of NR1
      is relevant to the central nervous system, in that a dramatic decrease in
      synthesis of this subunit and assembly of NMDARs is observed in cortical neurons
      treated with tunicamycin. The inhibition of NR1 synthesis is not due to changes
      in levels of mRNA but associated with the earliest stages in NMDAR biogenesis.
      The inhibition of N-glycosylation activates ER-specific stress responses in
      neurons, which include the ER-associated degradation (ERAD) mechanism responsible
      for differential and extremely efficient degradation of nonglycosylated NR1 by
      the proteasome after ubiquitination. Because this is an obligatory NMDAR
      component, the significant sensitivity of NR1 to ER stress will have important
      consequences on receptor function.

PMID- 17455307
TI  - Alpha-7 nicotinic acetylcholine receptor agonists selectively activate limbic
      regions of the rat forebrain: an effect similar to antipsychotics.
AB  - It is considered that activation of nicotinic alpha7 receptors (alpha7 nAChR) is
      useful for the treatment of cognitive disturbances in schizophrenia and
      Alzheimer's disease. Recently, selective alpha7 nAChR agonists have been
      discovered and are used to validate the alpha7 nAChR as a drug target for the
      treatment of cognitive disturbances in schizophrenia. One important feature
      shared by all known antipsychotics is their capacity to induce expression of the
      neuronal immediate-early gene c-fos in the limbic forebrain. Using two novel and
      selective alpha7 nAChR agonists, PNU-282987 and SSR180711, we investigated their
      ability to induce c-Fos expression in the limbic forebrain with particular
      emphasis on the same regions reported to be activated by antipsychotics. Both
      alpha7 nAChR agonists increased c-Fos dose-dependently in the prefrontal cortex
      and the shell of nucleus accumbens, while leaving the core of nucleus accumbens
      and the dorsolateral striatum unaffected. The accumbal and cortical effect of
      SSR180711 was blocked completely by pre-administration of the alpha7 nAChR
      antagonist methyllycaconitine. Also, SSR180711 displayed no c-Fos-inducing effect
      in alpha7 nAChR knock-out mice. In conclusion, these results show that selective
      pharmacologic stimulation of alpha7 nAChR function results in activation of
      forebrain regions similar to conventional antipsychotics.

PMID- 17455308
TI  - Postnatal neurogenesis in hippocampal slice cultures: early in vitro labeling of
      neural precursor cells leads to efficient neuronal production.
AB  - Neurogenesis continues throughout life in the hippocampus. To study postnatal
      neurogenesis in vitro, hippocampal slices from rats on postnatal day 5 (P5) were
      cultured on a porous membrane for 14 or 21 days. In the initial experiments,
      precursor cells were labeled with bromodeoxyuridine (BrdU) after 7 days in
      culture because hippocampal slices are generally used in experiments after 1-2
      weeks in culture. Fourteen days after labeling, however, only about 10% of BrdU
      labeled cells expressed neuronal markers, although in living rats, about 80% of
      cells labeled with BrdU on P5 had become neurons by P19. Next, rats were injected
      with BrdU 30 min before culture, after which hippocampal slices were cultured for
      14 days to examine the capacity of in vivo-labeled neural precursors to
      differentiate into neurons in vitro. In this case, more than two-thirds of BrdU
      labeled cells expressed neuronal markers, such as Hu, NeuN, and PSA-NCAM.
      Furthermore, precursor cells underwent early in vitro labeling by incubation with
      BrdU or a modified retrovirus vector carrying EGFP for 30 min from the beginning
      of the culture. This procedure resulted in a similar high rate of neuronal
      differentiation and normal development into granule cells. In addition, time
      lapse imaging with retrovirus-EGFP revealed migration of neural precursors from
      the hilus to the granule cell layer. These results indicate that in vivo- and
      early in vitro-labeled cultures are readily available ex vivo models for studying
      postnatal neurogenesis and suggest that the capacity of neural precursors to
      differentiate into neurons is reduced during the culture period.

PMID- 17455309
TI  - Sequential expression of cell-cycle regulators and Alzheimer's disease-related
      proteins in entorhinal cortex after hippocampal excitotoxic damage.
AB  - Growing evidence suggests that one of the earliest events in the neuronal
      degeneration of Alzheimer's disease (AD) is aberrant cell-cycle activation in
      postmitotic neurons, which may, in fact, be sufficient to initiate the
      neurodegenerative cascade. In the present study we examined whether cyclins and
      cyclin-dependent kinases, molecules normally associated with cell-cycle control,
      may be involved in delayed expression of altered Alzheimer's proteins in two
      interconnected areas, the entorhinal cortex (EC) and the dentate gyrus (DG),
      after a hippocampal excitotoxic lesion. Several cell-cycle proteins of the G1 and
      S phases and even of the G2 phase were found to be up-regulated in the EC after
      kainic acid evoked neuronal death in the hippocampus. In addition, we describe
      the progressive expression of two Alzheimer's-related proteins, PHF-1 and APP,
      which reached higher levels immediately after the increase in G1/S-phase markers.
      Hence, the results of the present study support the participation of cell-cycle
      dysregulation as a key component of the process that may ultimately lead to
      expression of AD proteins and neuronal death in a brain area when the target site
      for synaptic inputs in that area is damaged by an excitotoxic insult.

PMID- 17455310
TI  - Essential thrombocythemia in a child with elevated thrombopoietin concentrations
      and skeletal anomalies.
AB  - Essential thrombocythemia is a rare myleoproliferative disorder in pediatrics.
      This myleoproliferative disorder is characterized by excessive proliferation of
      megakaryocytes and sustained elevation of platelet count. Reactive thrombocytosis
      is a more common cause of elevated platelet counts among children. We describe a
      2-year-old child with essential thrombocythemia, skeletal anomalies, and elevated
      thrombopoietin concentrations. The child's mother was also subsequently diagnosed
      with essential thrombocythemia and had elevated thrombopoietin concentrations.
      Chromosomal studies on the mother, child and other family members were normal.

PMID- 17455311
TI  - Analysis of outcome for patients with mass lesions of the central nervous system
      due to Langerhans cell histiocytosis treated with 2-chlorodeoxyadenosine.
AB  - PURPOSE: To assess the activity and tolerability of 2-chlorodeoxyadenosine (2
      CDA) in treating mass lesions of the central nervous system (CNS) due to
      Langerhans cell histiocytosis (LCH). PATIENTS AND METHODS: The records of eight
      children and four adults with CNS LCH who were treated with 2-CDA were reviewed.
      The pattern of CNS disease included involvement of the hypothalamic-pituitary
      axis, gadolinium enhancing parenchymal as well as dural and choroid plexus based
      mass lesions, and atrophy. 2-CDA (5-13 mg/m(2)/day) was given on 3-5 consecutive
      days and repeated every 2-8 weeks for a period ranging from 3 to 12 months.
      RESULTS: Eight patients demonstrated a complete radiographic response to 2-CDA
      with resolution of all enhancing mass lesions and four patients showed a
      sustained, partial radiographic response. One patient died from a non-treatment
      related cause without evidence of LCH on autopsy. With a follow-up ranging from 2
      to 10 years after completion of therapy, the 11 surviving patients remain in
      continuous remission or are progression free. Prolonged bone marrow suppression
      was the most common toxicity (four patients). Permanent sequelae of CNS LCH, such
      as panhypopituitarism, diabetes insipidus (DI) and neurocognitive dysfunction,
      were not found to be reversible with 2-CDA therapy. CONCLUSIONS: 2-CDA is an
      active agent in patients with CNS LCH, with the possible exception of
      neurodegenerative disease, and should be further evaluated in a prospective multi
      center clinical trial for LCH patients with enhancing mass lesions of the CNS.

PMID- 17455312
TI  - X-linked lymphoproliferative disease with a novel SH2D1A gene mutation.

PMID- 17455313
TI  - Use of imatinib mesylate in a 15-month old with Philadelphia chromosome positive
      (Ph+) chronic myelogenous leukemia.

PMID- 17455314
TI  - Triple intrathecal therapy without cranial irradiation for central nervous system
      preventive therapy in childhood acute lymphoblastic leukemia.
AB  - BACKGROUND: To evaluate the treatment results of central nervous system
      preventive therapy (CNSP) with triple intrathecal therapy (TIT) alone in children
      with acute lymphoblastic leukemia (ALL). METHODS: We retrospectively studied a
      cohort of 59 patients with median follow-up time 50.6 months (range: 27-80
      months) at a single institution in Taiwan. Patients with ALL were classified in
      risk groups at diagnosis. TPOG-ALL-93 protocols and TPOG-ALL-2002 protocols were
      used. Both protocols were for multicenter studies in Taiwan and contained
      protocols for standard-risk (SR), high-risk (HR), and very-high-risk (VHR)
      patients. In this study, we used TIT alone for CNSP. In all ALL patients,
      methotrexate, hydrocortisone, and cytarabine were given at age-dependent doses.
      RESULTS: As of October 2006, patients had a 3-year event-free survival and an
      overall survival 89.4 +/- 4.1% (S.E.) and 93.1 +/- 3.3%, respectively. Under TIT
      no patients had complications such as seizure, encephalitis, or infection, and no
      morbidities like those caused by cranial irradiation. In this study, we used TIT
      alone for CNSP and had no CNS relapse. CONCLUSIONS: In the context of effective
      systemic therapy, TIT alone appears to be effective CNSP for most patients with
      ALL.

PMID- 17455315
TI  - CNS complications in children receiving chemotherapy or hematopoietic stem cell
      transplantation: retrospective analysis and clinical study of survivors.
AB  - BACKGROUND: Clinical studies analyzing CNS complications in pediatric oncology
      systematically are rare. PROCEDURE: In a single center retrospective analysis,
      CNS complications in 950 subsequent pediatric patients treated between 1992 and
      2004 by chemotherapy or hematopoietic stem cell transplantation (HSCT) were
      studied. Forty-six patients had pre-existing CNS diseases and were excluded. Out
      of the 904 remaining, 76 (8.4%) had 82 CNS complications. RESULTS: The most
      common manifestations were seizures (in 50.6% of the CNS episodes), altered
      states of consciousness, and motor deficits (in 47.5% of the episodes each). CNS
      complications were caused by infections (26.8%), toxicity (25.6%), neoplasma
      (13.4%), vascular (10.9%), and metabolic disturbances (8.5%). In 14.6%, the
      mechanism remained unclear. Patients (23.7%) died from the CNS event. Neoplastic
      disorders had the worst (50%) while metabolic the best (0% mortality) prognosis.
      Imaging techniques were the most effective diagnostic measures, followed by
      laboratory analysis, clinical examination, and CSF analysis. A neuro
      psychological (CBCL, CFT-1/-20-testing) examination could be done in 21 of 32
      long-term survivors. Seven had a major, 3 minor neurological impairment, 11 were
      normal in all tests. CONCLUSIONS: These data show that there is not one typical
      CNS complication, but a wide variety. There is no close connection between either
      underlying disease or symptoms and cause of the complication. Prognosis is
      variable. About two thirds of the long-term survivors could lead a normal life.

PMID- 17455316
TI  - Getting the numbers straight in pediatric MDS: distribution of subtypes after
      exclusion of down syndrome.

PMID- 17455317
TI  - Association of cell cycle-related gene products and NF-kappaB with clinical
      parameters in Langerhans cell histiocytosis.
AB  - BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder characterized
      by the accumulation of abnormal Langerhans cells in one or several organs where
      they cause local tissue damage. The pathophysiology is not well understood. The
      aim of this study was to examine expression of various gene products that play a
      role in cell cycle and cell death and to look for an association with the extent
      of the disease at the time of diagnosis and with "risk bone" involvement.
      PROCEDURE: Histologic slides from cases with biopsy proven disease were stained
      immunohistochemically for Bcl-2, caspase-3, Ki-67, p53, and nuclear factor-kappaB
      (NF-kappaB) and the results were quantitated and compared with the clinical
      extent of the disease. RESULTS: In patients with multisystem disease and "risk"
      bone involvement, a higher percentage of Langerhans cells stained with the anti
      apoptotic gene product Bcl-2 (P = 0.0004; P = 0.001 respectively) and a lower
      percentage of these cells stained with the apoptosis marker caspase-3 compared to
      patients with single system disease (P = 0.0001; P = 0.01 respectively).
      Proliferation marker Ki-67 was expressed more frequently in multisystem disease
      compared to single system disease (P = 0.02) but an association with "risk" bone
      involvement was not found. Expression of p53 and NF-kappaB did not discriminate
      between clinical subgroups. CONCLUSIONS: The findings suggest that cell
      proliferation and suppression of apoptosis may be mechanisms of cell survival in
      the more aggressive forms of LCH (multisystem, risk bone involvement).

PMID- 17455318
TI  - Bone marrow assessment in Langerhans cell histiocytosis.
AB  - BACKGROUND: Bone marrow changes and their relation to blood cytopenia in patients
      with Langerhans cell histiocytosis (LCH) have not been extensively studied to
      date. The aim of the present study was to characterize the bone marrow changes in
      LCH patients and to ascertain their relation to disease severity. METHODS: Fifty
      seven marrow samples of LCH patients were studied by conventional cytology,
      immunocytochemistry (ICC) and flow cytometry (FCM). RESULTS: On conventional
      cytology there was no significant difference between LCH cases and controls with
      respect to cellularity, number of monocytes and progenitor cells, and presence of
      histiocytes and hemophagocytosis. The numbers of nucleated cells, CD34(pos)
      cells, and CD14(pos) cells on FCM did not differ, either. The CD1a staining by
      ICC was positive in 14/41 LCH samples, and was consistently negative in controls.
      FCM staining for CD1a was positive in 12/54 samples, but also in 5/35 controls.
      The number of the CD1a(pos) cells in LCH marrows was usually very low (<10-20
      cells/slide by ICC, or <0.5% of the leukocytes by FCM). The CD1a staining was
      more frequently positive and more pronounced in patients with severe disease.
      CONCLUSIONS: The combination of conventional aspirate cytology with ICC (CD1a
      staining) appears to be the most reliable tool for bone marrow assessment in LCH.

PMID- 17455319
TI  - The absence of donor-derived IL-13 exacerbates the severity of acute graft-versus
      host disease following allogeneic bone marrow transplantation.
AB  - Acute graft versus host disease (aGVHD) after allogeneic bone marrow
      transplantation (allo-BMT) predominantly involves a Th1-type cytokine response.
      Interestingly, the Th2-cytokine, Interleukin-13 (IL-13), produced by alloreactive
      donor T cells in vitro was recently shown to correlate with clinical aGVHD
      severity. Using an established mouse model, we show that the systemic cytokine
      milieu following allo-BMT with IL-13-/- donors is characterized by decreases in
      serum Th2 cytokines and an increase in serum TNFalpha, and ultimately correlates
      with higher aGVHD mortality compared to allogeneic controls. In vitro studies
      further demonstrate that both exogenous and T cell-derived IL-13 can regulate
      TNFalpha production by macrophages following lipopolysaccharide stimulation.
      Thus, donor-derived IL-13 may have a role in modulating inflammatory cytokine
      release that is associated with aGVHD.

PMID- 17455320
TI  - Crystallographic characterization of several erythromycin A solvates: the
      environment of the solvent molecules in the crystal lattice.
AB  - Four solvates of erythromycin have been crystallographically characterized. The
      solvates of THF and dioxane are very similar but differ in notable ways. The
      isopropanol solvate exhibits uncommon modes of hydrogen bonding, which have
      previously been seen only in the erythomycin B hydrate. The methanol solvate is
      strikingly similar to the methanol solvate of 6-O-methyl erythromycin.

PMID- 17455321
TI  - Enhanced poly(ADP-ribose) polymerase-1 activation contributes to recombinant
      tissue plasminogen activator-induced aggravation of ischemic brain injury in
      vivo.
AB  - Recombinant tissue plasminogen activator (rt-PA) treatment improves functional
      outcome after acute ischemic stroke, inducing reperfusion by its thrombolytic
      activity. Conversely, there is evidence that rt-PA can mediate neuronal damage
      after ischemic brain injury in vivo. In addition to other mechanisms, enhancement
      of N-methyl-D-aspartate (NMDA) receptor signalling has been proposed to underlie
      rt-PA-mediated neurotoxicity. However, the role of poly(ADP-ribose) polymerase-1
      (PARP-1) activation, which mediates postischemic excitotoxic cell death, in rt-PA
      mediated aggravation of ischemic brain injury has not been established and was
      therefore addressed in this study. After permanent focal cerebral ischemia,
      intravenous rt-PA application significantly increased early postischemic PARP-1
      activation within ischemic hemispheres and infarct volumes compared with control
      mice without affecting cerebral blood flow. Rt-PA induced increase in PARP-1
      activation, and infarct volumes could be blocked by the PARP inhibitor 3
      aminobenzamide. Moreover, the rt-PA-induced increase in PARP-1 activation was
      also prevented by the NMDA antagonist MK-801. In summary, we demonstrate that rt
      PA treatment enhances postischemic PARP-1 activation, which contributes to rt-PA
      induced aggravation of ischemic brain injury in vivo. Furthermore, we provide
      evidence that NMDA receptor activation is required for rt-PA-mediated effects on
      postischemic PARP-1 activation.

PMID- 17455322
TI  - Formulation of spray-dried phenytoin loaded poly(epsilon-caprolactone)
      microcarrier intended for brain delivery to treat epilepsy.
AB  - This study evaluates the efficacy of the spray-drying technique in the
      bioengineering of phenytoin (PHT) containing poly(epsilon-caprolactone) (PCL)
      microcarrier intended for brain delivery for long-term treatment of epilepsy.
      Through orthogonally designed experiments, the optimal formulation and process
      variables for the preparation of PCL-microcarriers containing PHT were obtained.
      The produced microcarriers were characterized by coulter counter, scanning
      electron, scanning transmission electron microscopies, differential scanning
      calorimetry, powder X-ray diffraction, and in vitro release. The results showed
      that the produced microcarriers have a spherical structure, uniform size
      distribution, and a particle mean diameter of about 4.0 microm, which is suitable
      for brain delivery. The PHT was loaded as dispersed microcrystals within the PCL
      microcarriers. From this system, PHT was released slowly into a buffer solution
      for approximately 14 days without any burst effect. These data suggested that PHT
      containing spray-dried PCL-microcarrier may be a promising drug delivery system
      for local brain delivery and long-term treatment of pharmacoresistant epilepsy.

PMID- 17455324
TI  - Physical characterization of component particles included in dry powder inhalers.
      I. Strategy review and static characteristics.
AB  - The performance of dry powder aerosols for the delivery of drugs to the lungs has
      been studied extensively in the last decade. The focus for different research
      groups has been on aspects of the powder formulation, which relate to solid
      state, surface and interfacial chemistry, bulk properties (static and dynamic)
      and measures of performance. The nature of studies in this field, tend to be
      complex and correlations between specific properties and performance seem to be
      rare. Consequently, the adoption of formulation approaches that on a predictive
      basis lead to desirable performance has been an elusive goal but one that many
      agree is worth striving towards. The purpose of this paper is to initiate a
      discussion of the use of a variety of techniques to elucidate dry particle
      behavior that might guide the data collection process. If the many researchers in
      this field can agree on this, or an alternative, guide then a database can be
      constructed that would allow predictive models to be developed. This is the first
      of two papers that discuss static and dynamic methods of characterizing dry
      powder inhaler formulations.

PMID- 17455323
TI  - Brain-derived neurotrophic factor suppresses tunicamycin-induced upregulation of
      CHOP in neurons.
AB  - The accumulation of unfolded or misfolded proteins in the endoplasmic reticulum
      (ER) lumen triggers ER stress. ER stress initiates a number of specific
      compensatory signaling pathways including unfolded protein response (UPR). UPR is
      characterized by translational attenuation, synthesis of ER chaperone proteins
      such as glucose-regulated protein of 78 kDa (GRP78, also known as Bip), and
      transcriptional induction, which includes the activation of transcription factors
      such as activating transcriptional factor 6 (ATF6) and C/EBP homologous protein
      (CHOP, also known as growth arrest and DNA damage-inducible gene 153 [GADD153]).
      Sustained ER stress ultimately leads to cell death. ER functions are believed to
      be impaired in various neurodegenerative diseases, as well as in some acute
      disorders of the brain. Brain-derived neurotrophic factor (BDNF), a member of the
      neurotrophin family, functions as a neuroprotective agent and rescues neurons
      from various insults. The molecular mechanisms underlying BDNF neuroprotection,
      however, remain to be elucidated. We showed that CHOP partially mediated ER
      stress-induced neuronal death. BDNF suppressed ER stress-induced upregulation/
      nuclear translocation of CHOP. The transcription of CHOP is regulated by ATF4,
      ATF6, and XBP1; BDNF selectively blocked the ATF6/CHOP pathway. Furthermore, BDNF
      inhibited the induction of death receptor 5 (DR5), a transcriptional target of
      CHOP. Our study thus suggests that suppression of CHOP activation may contribute
      to BDNF-mediated neuroprotection during ER stress responses.

PMID- 17455325
TI  - Energetic aspects of diclofenac acid in crystal modifications and in solutions-
      mechanism of solvation, partitioning and distribution.
AB  - Temperature dependency of saturated vapor pressure and heat capacity for the
      diclofenac acid (Form II) were measured and thermodynamic functions of
      sublimation calculated (DeltaG(sub)(298) = 49.3 kJ x mol(-1); DeltaH(sub)(298) =
      115.6 +/- 1.3 kJ x mol(-1); DeltaS(sub)(298) = 222 +/- 4 J x mol(-1) x K(-1)).
      Crystal polymorphic Forms I (P2(1)/c) and II (C2/c) of diclofenac acid have been
      prepared and characterized by X-ray diffraction experiments. The difference
      between crystal lattice energies of the two forms were obtained by solution
      calorimetry: DeltaDeltaH(sol)(I --> II) = 1.6 +/- 0.4 kJ x mol(-1). Temperature
      dependencies of the solubility in buffers with pH 2.0 and 7.4, n-octanol and n
      hexane were measured. The thermodynamic functions of solubility, solvation, and
      transfer processes were deduced. Specific and non-specific solvation terms were
      distinguished using the transfer from the "inert" n-hexane to the other solvents.
      The transfer of diclofenac acid molecules from the buffers to n-octanol
      (partitioning and distribution) is an entropy driven process.

PMID- 17455326
TI  - Increases in expression of 14-3-3 eta and 14-3-3 zeta transcripts during
      neuroprotection induced by delta9-tetrahydrocannabinol in AF5 cells.
AB  - The molecular mechanisms involved in N-methyl-D-aspartate (NMDA)-induced cell
      death and Delta9-tetrahydrocannabinol (THC)-induced neuroprotection were
      investigated in vitro with an AF5 neural progenitor cell line model. By
      microarray analysis, Ywhah, CK1, Hsp60, Pdcd 4, and Pdcd 7 were identified as
      being strongly regulated by both NMDA toxicity and THC neuroprotection. The 14-3
      3 eta (14-3-3eta; gene symbol Ywhah) and 14-3-3 zeta (14-3-3zeta; gene symbol
      Ywhaz) transcripts were deceased by NMDA treatment and increased by THC treatment
      prior to NMDA, as measured by cDNA microarray analysis and quantitative real-time
      RT-PCR. Other 14-3-3 isoforms were unchanged. Whereas up-regulation of 14-3-3zeta
      expression was observed 30 min after treatment with THC plus NMDA, down
      regulation by NMDA alone was not seen until 16 hr after treatment. By Western
      blotting, THC increased 14-3-3 protein only in cells that were also treated with
      NMDA. Overexpression of 14-3-3eta or 14-3-3zeta by transient plasmid transfection
      increased 14-3-3 protein levels and decreased NMDA-induced cell death. These data
      suggest that increases in 14-3-3 proteins mediate THC-induced neuroprotection
      under conditions of NMDA-induced cellular stress.

PMID- 17455327
TI  - QNQKE targeting motif for the SMN-Gemin multiprotein complexin neurons.
AB  - Spinal muscular atrophy (SMA) is a heritable neurodegenerative disease affecting
      motor neurons that is caused by the impaired expression of the full-length form
      of the survival of motor neuron protein (SMN), which may have a specialized
      function in neurons related to mRNA localization. We have previously shown that a
      population SMN complexes contain Gemin ribonucleoproteins and traffic in the form
      of granules to neuronal processes and growth cones of cultured neurons. A QNQKE
      sequence within exon 7 has been shown to be necessary for both cytoplasmic
      localization of SMN and axonal function. Here we show that the QNQKE sequence can
      influence the nucleocytoplasmic distribution of the SMN-Gemin complex and its
      localization into neuronal processes. QNQKE exerted a stronger effect on SMN
      localization in primary neurons compared with COS-7 cells. By using double-label
      fluorescence in situ hybridization and immunofluorescence, SMN granules within
      neuronal processes colocalized with poly-(A) mRNA and PABP. These findings
      provide further evidence in support of a neuronal function for SMN and motivation
      to investigate for impaired assembly and/or localization of mRNP complexes as an
      underlying cause of SMA.

PMID- 17455328
TI  - Thermal expansion of organic crystals and precision of calculated crystal
      density: a survey of Cambridge Crystal Database.
AB  - True density is a physical property of both fundamental and practical importance
      to the study of pharmaceutical powders. True density may be calculated from
      crystal structure. However, precision of such calculated density is not well
      understood. Furthermore, thermal expansion properties of organic crystals have
      rarely been characterized. A survey of Cambridge Crystal Database is conducted to
      assess (1) precision of calculated crystal density from crystal structure; (2)
      thermal expansion properties of organic crystals. It is shown that calculated
      crystal density exhibits, on average, a relative standard deviation (RSD) of
      approximately 0.4%. It is found that crystal density generally increases linearly
      with decreasing temperature provided no phase change occurs. Slope of the line,
      termed thermal density gradient, of organic crystals ranges between 0.04 and 1.74
      mg cm(-3) K(-1) with an average of approximately 0.2 mg cm(-3) K(-1). It is shown
      that majority polymorph pairs exhibit significantly different thermal expansion
      behavior and their density-temperature lines can cross. This likely contributes
      to the less than perfect prediction of relative stability of polymorphs at
      ambient temperature using the density rule.

PMID- 17455329
TI  - Structure, solubility, screening, and synthesis of molecular salts.
AB  - The preparation of molecular salts as potential delivery vehicles for
      pharmaceutically active compounds is more common than current appreciation of the
      phenomena governing the solubility and isolation of salts suggests. In addition,
      it would appear that there are no reported measurements on a large enough data
      set for a serious structure-property relationship analysis to have been performed
      for this class of material. This means that at present, the ability to predict
      which salt forms will have desirable physical properties is essentially
      nonexistent. The work reported here sets out to explore these issues using new
      data on 17 salts obtained from a screen performed on the basic pharmaceutical
      ephedrine. The importance of solvent choice in salt formation, of salt selection
      in the control of bioavailability and of ternary phase equilibria in salt
      isolation and the relationship between a number of measured and calculated
      crystal properties are illustrated and discussed. The consequences of these
      relations for the general design, implementation, interpretation, and scale-up of
      salts screens are also explored.

PMID- 17455330
TI  - Solvent influences on metastable polymorph lifetimes: real-time interconversions
      using energy dispersive X-ray diffractometry.
AB  - Solvent influences on the crystallization of polymorph and hydrate forms of the
      nootropic drug piracetam (2-oxo-pyrrolidineacetamide) were investigated from
      water, methanol, 2-propanol, isobutanol, and nitromethane. Crystal growth
      profiles of piracetam polymorphs were constructed using time-resolved diffraction
      snapshots collected for each solvent system. Measurements were performed by in
      situ energy dispersive X-ray diffraction recorded in Station 16.4 at the
      synchrotron radiation source (SRS) at Daresbury Laboratory, CCLRC UK.
      Crystallizations from methanol, 2-propanol, isobutanol, and nitromethane
      progressed in a similar fashion with the initial formation of form I which then
      converted relatively quickly to form II with form III being generated upon
      further cooling. However, considerable differences were observed for the
      polymorphs lifetime and both the rate and temperature of conversion using the
      different solvents. The thermodynamically unstable form I was kinetically favored
      in isobutanol and nitromethane where traces of this polymorph were observed below
      10 degrees C. In contrast, the transformation of form II and subsequent growth of
      form III were inhibited in 2-propanol and nitromethane solutions. Aqueous
      solutions produced hydrate forms of piracetam which are different from the
      reported monohydrate; this crystallization evolved through successive generation
      of transient structures which transformed upon exchange of intramolecular water
      between the liquid and crystalline phases.

PMID- 17455331
TI  - Investigations on solid-solid phase transformation of 5-methyl-2-[(4-methyl-2
      nitrophenyl)amino]-3-thiophenecarbonitrile.
AB  - Solid-solid transformation of 5-methyl-2-[(4-methyl-2-nitrophenyl)amino]-3
      thiophenecarbonitrile from the dark-red to the red form was investigated. By
      controlled crystallization, the dark-red form was prepared and the crystals were
      sieved into fractions: coarse (>250 microm), medium (125-177 microm), and fine
      (<88 microm). The transformation rate order (fastest to slowest) of the different
      fractions is coarse > medium > fine. However, milling accelerates the
      transformation, that is, smaller particles generated by milling transforms
      faster. Furthermore, ethanol vapor annealing slows both the transformation of the
      coarse and medium fractions, especially the latter. Therefore, the mechanism of
      transformation is not directly related to the crystal-size and most likely
      related to the amount and activity of the defects in the crystals. The three
      dimensional (3-D) Avrami-Erofe'ev model, know as "random nucleation and growth"
      model, fits the kinetics of coarse fraction best. Higher relative humidity
      accelerates the transformation dramatically even though the compound is highly
      hydrophobic. With minimal hydrogen bonding interaction involved, it appears even
      small amounts of water can serve as a nucleation catalyst by binding to the
      crystal surface, especially at defect sites, thus increasing the molecular
      mobility of these sites, promoting the transformation to the second phase and
      thereby increasing the transformation rate.

PMID- 17455332
TI  - Signaling properties of stratum oriens interneurons in the hippocampus of
      transgenic mice expressing EGFP in a subset of somatostatin-containing cells.
AB  - GABAergic interneurons constitute a heterogeneous group of cells that exert a
      powerful control on network excitability and are responsible for the oscillatory
      behavior crucial for information processing in the brain. These cells have been
      differently classified according to their morphological, neurochemical, and
      physiological characteristics. Here, whole cell patch clamp recordings were used
      to further characterize, in transgenic mice expressing EGFP in a subpopulation of
      GABAergic interneurons containing somatostatin (GIN mice), the functional
      properties of EGFP-positive cells in stratum oriens of the CA1 region of the
      hippocampus, in slice cultures obtained from P8 old animals. These cells showed
      passive and active membrane properties similar to those found in stratum oriens
      interneurons projecting to stratum lacunosum-moleculare. Moreover, they exhibited
      different firing patterns that were maintained upon membrane depolarization:
      irregular (48%), regular (30%), and clustered (22%). Trains of action potentials
      in interneurons evoked in a minority of principal cells (3/45) small amplitude
      GABAergic currents that at 20 Hz underwent short-term depression. In contrast,
      excitatory connections between principal cells and EGFP-positive interneurons
      were highly reliable (17/55) and exhibited a frequency and use-dependent
      facilitation particularly in the gamma band. In addition, recordings from paired
      of interconnected EGFP-positive cells revealed in 47% of the cases electrical
      coupling, which was abolished by carbenoxolone (200 microM). On average, the
      coupling coefficient was 0.21 +/- 0.07. When electrical coupling was particularly
      strong it acted as a powerful low-pass filter, thus contributing to alter the
      output of individual cells. In conclusion, it appears that the dynamic
      interaction between cells with various firing patterns could differently affect
      GABAergic signaling, leading, as suggested by simulation data, to a wide range of
      interneuronal communication within the hippocampal network.

PMID- 17455333
TI  - Role of dCA3 efferents via the fimbria in the acquisition of a delay nonmatch to
      place task.
AB  - Dorsal CA3, but not dorsal CA1, lesioned rats are impaired in the acquisition of
      a delay nonmatch to place task. In this study, dorsal CA3 efferent fibers in the
      fimbria were transected; while taking care to spare afferent fibers from the
      medial septum. Neurophysiological, anatomical tracing, and histochemical data
      suggest that the transection was selective to dorsal CA3 efferent fibers and
      spared afferents from the medial septum. Rats showed a deficit for acquisition,
      but not for performance once learned. One possible explanation is that a small
      change to the cholinergic inputs to dCA3 caused by a decrease in dorsal CA3
      efferent signals reaching the medial septum may impair new learning but not
      performance of a task once learned.

PMID- 17455334
TI  - The units of thought.
AB  - That associative processing provides the vehicle of thought is a long-standing
      idea. We describe here observations from cognitive neuroimaging that elucidate
      the neural processing that mediates this element. This account further allows a
      more specific ascription of a cognitive function to the brain's "default"
      activity in mindwandering. We extend this account to argue that one primary
      outcome of associative processing is the generation of predictions, which
      approximate the immediately relevant future and thus facilitate perception,
      action, and the progression of thought.

PMID- 17455335
TI  - Hydrates and solid-state reactivity: a survey of beta-lactam antibiotics.
AB  - Crystalline hydrates of hydrolytically susceptible pharmaceuticals are commonly
      encountered, and are particularly prevalent in the beta-lactam class of
      antibiotics. In order to rationalize how the apparent chemical incompatibility
      between water and beta-lactams is reduced through crystallization, a review of
      the published literature and available structural information on the solid state
      stability was undertaken. A search in the CSD yielded a total of 32 crystal
      structures of water-containing beta-lactams which were examined and classified in
      terms of hydrogen-bonded networks. In most cases the waters of hydration in the
      single crystal structures were found to fulfill structural roles and were not
      sufficiently close in proximity to react with the beta-lactam ring. Published
      data for the solid-state of several hydrates were also considered. In general,
      the stability data indicate high thermal stability for the crystalline hydrates.
      Moreover, even when water molecules are in appropriate proximity and orientation
      with respect to the beta-lactam moiety for a reaction to occur, the crystalline
      solids remain stable. The use of the crystal structure information along with
      computational modeling suggests that a combination of proximal relationships,
      steric and mechanistic arguments can explain the observed solid-state stability
      of crystalline beta-lactam hydrates.

PMID- 17455336
TI  - Demonstration of a shear-based solid-state phase transformation in a small
      molecular organic system: chlorpropamide.
AB  - Elucidation of the mechanisms for mechanically activated phase transformations of
      API are necessary for progress in materials and process understanding. The
      mechanically induced solid-state transformation between the A and C enantiotropes
      of the anti-diabetic drug chlorpropamide (C(10)H(13)ClN(2)O(3)S) was
      investigated. The structure of the high temperature stable phase (form C) was
      solved using powder X-ray data. Transmission powder X-ray diffraction (PXRD) and
      Raman spectroscopy were used for in situ quantification and analysis of the phase
      interconversion that occurs as a function of applied pressure during compaction.
      Each polymorph was observed to undergo a solid-state transition, which increased
      with pressure to a maximum extent that corresponded with the consolidation limit
      of the respective bulk powder. Neither form was observed to convert under
      hydrostatic pressure, suggesting a shear dependence for interconversion at
      compaction pressures. Examination of the two crystallographic structures
      indicated that both forms have a common slip system and preserved molecular
      positions. It is suggested that the transformation of either form is allowed when
      resolved shear stresses initiate deformation, causing lattice distortion, which
      allows the simultaneous reconformation of molecules.

PMID- 17455337
TI  - Solving molecular crystal structures from X-ray powder diffraction data: the
      challenges posed by gamma-carbamazepine and chlorothiazide N,N,-dimethylformamide
      (1/2) solvate.
AB  - The crystal structures of gamma-carbamazepine (P1, Z' = 4) and chlorothiazide N,N
      dimethylformamide solvate (1/2) (P2(1)/c, Z' = 2) have been determined from
      synchrotron and laboratory X-ray powder diffraction data, respectively, using
      simulated annealing. Both structures represent a significant challenge for global
      optimization and the successful solutions and subsequent refinements highlight
      the ever-expanding range of applicability of powder diffraction to structural
      problems of pharmaceutical relevance.

PMID- 17455338
TI  - Macromolecule release from monodisperse PLG microspheres: control of release
      rates and investigation of release mechanism.
AB  - Novel macromolecular therapeutics such as peptides, proteins, and DNA are
      advancing rapidly toward the clinic. Because of typically low oral
      bioavailability, macromolecule delivery requires invasive methods such as
      frequently repeated injections. Parenteral depots including biodegradable polymer
      microspheres offer the possibility of reduced dosing frequency but are limited by
      the inability to adequately control delivery rates. To control release and
      investigate release mechanisms, we have encapsulated model macromolecules in
      monodisperse poly(D,L-lactide-co-glycolide) (PLG) microspheres using a double
      emulsion method in combination with the precision particle fabrication technique.
      We encapsulated fluorescein-dextran (F-Dex) and sulforhodamine B-labeled bovine
      serum albumin (R-BSA) into PLG microspheres of three different sizes: 31, 44, and
      80 microm and 34, 47, and 85 microm diameter for F-Dex and R-BSA, respectively.
      The in vitro release profiles of both compounds showed negligible initial burst.
      During degradation and release, the microspheres hollowed and swelled at critical
      time points dependant upon microsphere size. The rate of these events increased
      with microsphere size resulting in the largest microspheres exhibiting the
      fastest overall release rate. Monodisperse microspheres may represent a new
      delivery system for therapeutic proteins and DNA and provide enhanced control of
      delivery rates using simple injectable depot formulations.

PMID- 17455339
TI  - Dielectric relaxation and crystallization of ultraviscous melt and glassy states
      of aspirin, ibuprofen, progesterone, and quinidine.
AB  - Molecular relaxation in ultraviscous melt and glassy states of aspirin,
      ibuprofen, progesterone, and quinidine has been studied by dielectric
      spectroscopy. The asymmetric relaxation spectra is characterized by the
      Kohlrausch distribution parameter of 0.46 +/- 0.02 for aspirin to 0.67 +/- 0.02
      for progesterone. The dielectric relaxation time varies with the temperature, T,
      according to the Vogel-Fulcher-Tammann Equation, log(10)(tau(0)) = A(VFT) +
      [B(VFT)/(T - T(0))], where A(VFT), B(VFT), and T(0) are empirical constants. The
      extrapolated tau(0) at calorimetric glass-softening temperature is close to the
      value expected. The equilibrium permittivity, epsilon(0), is lowest for ibuprofen
      which indicates an antiparallel orientation of dipoles in its liquid's hydrogen
      bonded structure. A decrease in epsilon(0) with time shows that ultraviscous
      aspirin, progesterone, and quinidine begin to cold-crystallize at a relatively
      lower temperature than ibuprofen. epsilon(0) of the cold-crystallized phases are,
      4.7 for aspirin at 290 K, 2.55 for ibuprofen at 287 K, 2.6 for progesterone at
      320 K, and 3.2 for quinidine at 375 K. It is argued that hydrogen-bonding, the
      Kohlrausch parameter, extent of localized motions and the long-range diffusion
      times all determine the physical and chemical stability of an amorphous
      pharmaceutical during storage.

PMID- 17455340
TI  - Polymorphism of Alprazolam (Xanax): a review of its crystalline phases and
      identification, crystallographic characterization, and crystal structure of a new
      polymorph (form III).
AB  - A new polymorphic form of Alprazolam (Xanax), 8-chloro-1-methyl-6-phenyl-4H
      [1,2,4]triazolo-[4,3-alpha][1,4]benzodiazepine, C(17)H(13)ClN(4), has been
      investigated by means of X-ray powder diffraction (XRPD), single crystal X-ray
      diffraction, and differential scanning calorimetry (DSC). This polymorphic form
      (form III) was obtained during DSC experiments after the exothermic
      recrystallization of the melt of form I. The crystal unit cell dimensions for
      form III were determined from diffractometer methods. The monoclinic unit cell
      found for this polymorph using XRPD after indexing the powder diffractogram was
      confirmed by the cell parameters obtained from single crystal X-ray
      diffractometry on a crystal isolated from the DSC pans. The single crystal unit
      cell parameters are: a = 28.929(9), b = 13.844(8), c = 7.361(3) angstroms, beta =
      92.82(3) degrees , V = 2944(2) angstroms(3), Z = 8, space group P2(1) (No.4), Dx
      = 1.393 Mg/m(3). The structure obtained from single crystal X-ray diffraction was
      used as initial model for Rietveld refinement on the powder diffraction data of
      form III. The temperature phase transformations of alprazolam were also studied
      using high temperature XRPD. A review of the different phases available in the
      Powder Diffraction File (PDF) database for this drug is described bringing some
      clarification and corrections.

PMID- 17455341
TI  - The effect of annealing on the stability of amorphous solids: chemical stability
      of freeze-dried moxalactam.
AB  - The objective of this study was to investigate the effect of annealing on the
      chemical stability and calorimetric structural relaxation times of freeze-dried
      moxalactam. Moxalactam disodium was freeze dried with 12% mannitol and split into
      several batches after freeze drying. One batch was held as a control while others
      were subjected to a further heating (annealing) treatment at 60 degrees C, 70
      degrees C, and 80 degrees C for different periods of time. Isothermal
      microcalorimetry studies using thermal activity monitor (TAM) were performed on
      the freeze-dried samples to measure relaxation times (tau) and stretched
      exponential values (beta). Modulated DSC experiments were carried out to
      determine T(g) and DeltaC(P) for moxalactam-12% w/w mannitol systems at various
      moisture contents to allow extrapolation of these quantities to zero residual
      moisture. Storage stability studies were performed at 25 degrees C, 40 degrees C
      and 50 degrees C. Decarboxylated moxalactam and parent contents after various
      storage times were measured by reverse phase HPLC. Annealing moxalactam-12%
      mannitol amorphous systems improved chemical stability of moxalactam and reduced
      molecular mobility, as measured by TAM. Moxalactam-12% w/w mannitol systems
      annealed at higher temperatures and for longer times had higher tau(beta) values
      than the "control" sample, with tau(beta) values increasing as annealing
      temperature increased. Additionally, tau(beta) value increased as annealing time
      at the same temperature increased. These observations indicated that higher
      temperature annealing decreased molecular mobility in the glass, as expected.
      Further, chemical stability improved as annealing temperatures and annealing
      times increased. For example, the rate of decarboxylation of the sample annealed
      at 70 degrees C for 8 h was roughly 1.7 times lower than the "control." Note that
      in spite of degradation during the annealing process, the level of degradation at
      the end of storage is actually less in the annealed sample than in the control
      sample; thus, annealing can result in samples having less degradation at the end
      of a storage period. Chemical stability and relaxation times are correlated, thus
      indicating that molecular mobility and structural relaxation time are coupled.

PMID- 17455342
TI  - Sudden rise of crystal growth rate of nifedipine near T(g) without and with
      polyvinylpyrrolidone.
AB  - The crystal growth of nifedipine in the beta polymorph has been measured from
      T(g) + 50 to T(g) - 20 K, where T(g) = 315 K is the glass transition temperature.
      A sudden 10-fold rise of growth rate was observed as the temperature decreased
      from above to below T(g) accompanied by a change of growth morphology. This is
      the same phenomenon reported by Oguni and coworkers [Hikima T, Adachi Y, Hanaya
      M, Oguni M. 1995. Phys Rev B 52:3900-3908] for other compounds of lower T(g). The
      phenomenon persisted in the presence of 1% polyvinylpyrrolidone (PVP). The
      presence of 1% or 2% PVP had little effect on the growth rate near T(g) + 50 K,
      but reduced the growth rate by 100-fold at T(g) + 9 K. These kinetic features are
      relevant to predicting the stability of amorphous drugs.

PMID- 17455343
TI  - Analysis of known crystals to design polymorph prediction strategies.
AB  - Computational analysis of known crystals was used to provide insight into
      polymorph prediction strategies. It was hypothesized that intermolecular
      crystalline interactions are inadequately accounted for in current computational
      strategies. The QEq method of partial charge assignments was applied to the
      crystal milieu (CMc) and to the isolated molecule (IMc). For 90 known crystal
      structures, these two partial charging methods showed that the unit cell energy
      was almost always lower (more stable) with CMc partial charge assignments. In
      simulations on a model drug, the CMc charging re-ranked the unit cell energies of
      possible polymorphs in a way that aided the identification of physically
      reasonable packings more easily than IMc. Decomposing the unit cell energy for
      known crystals showed that the cohesive IMc deviation from CMc was dominant. On
      the other hand, for simulations, the corresponding IMc conformational component
      of unit cell energy dominates when conformational adaptive strategies (CA) are
      used; this was not apparent with rigid-body simulations (RB). Furthermore,
      evidence is presented that polymorph strategies that use unit cell energy for
      optimizing are especially prone to this undesired conformational bias.
      Suggestions are made for polymorph strategies that might enhance the probability
      of identifying physically relevant polymorphs in the future.

PMID- 17455344
TI  - Solid-state chemistry of ambroxol theophylline-7-acetate.
AB  - Ambroxol theophylline-7-acetate (ACE) is the salt obtained by reaction of
      equimolar amounts of ambroxol (AMB), a drug showing mucolytic and expectorant
      properties, and theophylline-7-acetic acid (TAA), a xanthine derivative with
      specific bronchodilator activity. ACE is used for the treatment of bronchial and
      pulmonary diseases (bronchitis, asthma, emphysema, chronic obstructive disease).
      Recrystallization experiments of ACE resulted in the isolation of two polymorphs
      (monotropically related) and four solvated forms. X-ray diffractometry, DSC, TGA,
      and HSM techniques were used to investigate the forms that are obtained by
      thermal desolvation of the solvates. The phase diagram of the TAA-AMB binary
      system was constructed by performing thermal analyses on mixtures of TAA-AMB and
      of each component plus the interaction compound (TAA-ACE and ACE-AMB). The
      Schroeder-Van Laar equation proved to be a very useful tool for checking the
      consistency between the experimental data and the theoretical model related to
      the general system, showing complete miscibility in the liquid phase and complete
      immiscibility in the solid phase.

PMID- 17455345
TI  - FDA perspective on clinical trial design for femoropopliteal stent correction of
      peripheral vascular insufficiency cardiovascular devices.

PMID- 17455346
TI  - Crystallization pathways and kinetics of carbamazepine-nicotinamide cocrystals
      from the amorphous state by in situ thermomicroscopy, spectroscopy, and
      calorimetry studies.
AB  - The work presented here was motivated by the premise that the amorphous state
      serves as a medium to study cocrystal formation. The molecular mobility inherent
      to amorphous phases can lead to molecular associations between different
      components such that a single crystalline phase of multiple components or
      cocrystal is formed. Cocrystallization pathways and kinetics were investigated
      from amorphous equimolar phases of carbamazepine and nicotinamide using hot-stage
      polarized microscopy (HSPM), hot-stage Raman microscopy (HSRM), differential
      scanning calorimetry (DSC), and X-ray powder diffraction (XRPD). Nonisothermal
      studies revealed that amorphous phases generate cocrystals and that thermal
      history affects crystallization pathways in significant ways. Two different
      pathways to cocrystal formation from the amorphous phase were identified: (1) at
      low heating rates (3 degrees C/min) a metastable cocrystalline phase initially
      nucleates and transforms to the more stable cocrystalline phase of CBZ-NCT, and
      (2) at higher heating rates (10 degrees C/min) individual components crystallize,
      then melt and the stable cocrystalline phase nucleates and grows from the melt.
      Isothermal studies above the T(g) of the amorphous equimolar phase also confirm
      the nucleation of a metastable cocrystalline phase from the amorphous state
      followed by a solid phase mediated transformation to the stable cocrystalline
      phase. Cocrystallization kinetics were measured by image analysis and by thermal
      analysis from small samples and are described by the Avrami-Erofeev model. These
      findings have important implications for the use of amorphous phases in the
      discovery of cocrystals and to determine the propensity of cocrystallization from
      process-induced amorphization.

PMID- 17455347
TI  - David James William Grant (1937-2005).

PMID- 17455348
TI  - Insensitivity of compaction properties of brittle granules to size enlargement by
      roller compaction.
AB  - Pharmaceutical granules prepared by roller compaction often exhibit significant
      loss of tabletability, that is, reduction in tensile strength, when compared to
      virgin powder. This may be attributed to granule size enlargement for highly
      plastic materials, for example, microcrystalline cellulose. The sensitivity of
      powder compaction properties on granule size variations impacts the robustness of
      the dry granulation process. We hypothesize that such sensitivity of compaction
      properties on granule size is minimum for brittle materials because extensive
      fracture of brittle granules during compaction minimizes differences in initial
      granule size. We tested the hypothesis using three common brittle excipients.
      Results show that the fine (44-106 microm), medium (106-250 microm), and coarse
      (250-500 microm) granules exhibit essentially identical tabletability below a
      certain critical compaction pressure, 100, 140, and 100 MPa for spray-dried
      lactose monohydrate, anhydrous dibasic calcium phosphate, and mannitol,
      respectively. Above respective critical pressure, tabletability lines diverge
      with smaller granules exhibiting slightly higher tablet tensile strength at
      identical compaction conditions. Overall, tabletability of brittle granules is
      insensitive to granule size enlargement. The results provide a scientific basis
      to the common practice of incorporating brittle filler to a typical tablet
      formulation processed by roller compaction granulation.

PMID- 17455349
TI  - Microenvironmental pH modulation in solid dosage forms.
AB  - There are many reports in the literature referring to the effect of
      microenvironmental pH on solid dosage form performance, particularly stability
      and dissolution profiles. Several techniques have been proposed for the
      measurement of the microenvironmental pH. Those techniques use certain
      assumptions and approximations and many of them employ a solution calibration
      curve of a probe to predict hydrogen ion activity in a substantially dry solid.
      Despite the limitation of the methodology, it is clear from the literature that
      microenvironmental pH has a significant impact on stability of compounds which
      demonstrate pH dependent stability in solution. Degradation kinetics of such
      compounds, and in some cases degradation profile as well, are dependent on the
      microenvironmental pH of the solid. Modulation of the microenvironmental pH
      through the use of pH modifiers can hence prove to be a very effective tool in
      maximizing solid dosage form stability. Judicial selection of the appropriate pH
      modifier, its concentration and the manufacturing process used to incorporate the
      pH modifier is necessary to enhance stability. Control of microenvironmental pH
      to maximize stability can be achieved without the use of pH modifier in some
      cases if an appropriate counter ion is used to provide an inherently optimal pH
      for the salt. Microenvironmental pH modulation was also shown to control the
      dissolution profile of both immediate and controlled release dosage forms of
      compounds with pH dependent solubility. The pH modifiers have been used in
      conjunction with high energy or salt forms in immediate release formulations to
      minimize the precipitation of the less soluble free form during initial
      dissolution. Additionally, pH modifiers were utilized in controlled release
      dosage forms of weakly basic drugs which exhibit diminished release in
      dissolution media with high pH. The incorporation of acidic pH modifiers in the
      controlled release formulation increases the solubility of the basic drug even as
      the high pH dissolution medium enters into the dosage form hence increasing drug
      release rate.

PMID- 17455350
TI  - Processing-induced phase transitions of theophylline--implications on the
      dissolution of theophylline tablets.
AB  - Aqueous wet massing of stable anhydrous theophylline (A) with
      polyvinylpyrrolidone (PVP) resulted in its complete transformation to
      theophylline monohydrate (M). Drying at 45 degrees C, resulted in the formation
      of metastable anhydrous theophylline (A*) which then transformed to A. PVP, a
      known crystallization inhibitor, was effective in inhibiting the A* --> A
      transition. The higher molecular weight polymer, PVP K90, was more effective in
      inhibiting the A* --> A transition as compared to PVP K17. The disappearance of
      M, and the formation of A* and A was simultaneously monitored by XRD. An increase
      in the drying temperature from 45 to 55 degrees C accelerated the A* --> A
      transition. In granules prepared by the high-shear process, approximately 50% of
      theophylline existed as A and the rest as A*. In contrast, the fluid-bed
      granulation process yielded granules containing only A. Thus, the physical form
      of theophylline in tablets was influenced by the molecular weight of the binding
      agent, the granulation method, and the drying temperature. Using A as the
      starting material, tablets were manufactured by high-shear aqueous wet
      granulation process and the A* content was quantified. These tablets were stored
      under various relative humidity (RH) conditions at 25 degrees C for 2 weeks.
      Storage at RH >or= 33% caused complete A* --> A conversion accompanied by a
      pronounced decrease in the initial dissolution rate indicating that phase
      transitions during processing and storage can have a significant influence on
      product performance.

PMID- 17455351
TI  - Assessment of defects and amorphous structure produced in raffinose pentahydrate
      upon dehydration.
AB  - The progressive conversion of crystalline raffinose pentahydrate to its amorphous
      form by dehydration at 60 degrees C, well below its melting temperature, was
      monitored by X-ray powder diffraction over a period of 72 h. The presence of
      defects within the crystal structure and any amorphous structure created was
      determined computationally by a total diffraction method where both coherent long
      range crystalline order and incoherent short-range disorder components were
      modeled as a single system. The data were analyzed using Rietveld, pair
      distribution function (PDF), and Debye total diffraction methods. Throughout the
      dehydration process, when crystalline material was observed, the average long
      range crystal structure remained isostructural with the original pentahydrate
      material. Although the space group symmetry remained unchanged by dehydration,
      the c-axis of the crystal unit cell exhibited an abrupt discontinuity after
      approximately 2 h of drying (loss of one to two water molecules). Analysis of
      diffuse X-ray scattering revealed an initial rapid build up of defects during the
      first 0.5 h with no evidence of any amorphous material. From 1-2 h of drying out
      to 8 h where the crystalline structure is last observed, the diffuse scattering
      has both amorphous and defect contributions. After 24 h of drying, there was no
      evidence of any crystalline material remaining. It is concluded that the removal
      of the first two waters from raffinose pentahydrate created defects, likely in
      the form of vacancies, that provided the thermodynamic driving force and disorder
      for subsequent conversion to the completely amorphous state.

PMID- 17455352
TI  - The 3-D model: experimental testing of the parameters d, e, and omega and
      validation of the analysis.
AB  - The aim of the study was to evaluate the parameters d, e, and omega for their
      significance in compression data analysis. Materials with predominantly different
      compression properties were used and tableting data were obtained with an
      instrumented eccentric and rotary tableting machine. The parameters time
      plasticity (d), pressure plasticity (e), and the twisting angle (omega), an
      indicator of fast elastic decompression, were derived by 3-D modeling. The Peak
      Offset-Time, the pressure-time function parameters, the Heckel slope, normalized
      compaction (E2(norm)) and elastic energy (E3(norm)), and fast elastic recovery
      (FER), which are well known tableting parameters, were calculated from the
      tableting data. The plastic microhardness of the tablets was determined from
      using microindentation. The results revealed that d is influenced by speed, e
      correlates with microhardness, and omega correlates with the Elastic modulus (E).
      Thus, for all three 3-D model parameters an experimental basis is given. The
      validation showed that d correlates with the Peak-Offset-Time and the pressure
      time function parameters, e correlates with the Heckel slope and E2(norm), and
      omega correlates with E3(norm) and FER of the tablets. The significance of the
      three parameters is fully given. It is no longer necessary to use two separate
      methods to differentiate between time- and pressure-dependent deformations.

PMID- 17455353
TI  - Transformation of pharmaceutical compounds upon milling and comilling: the role
      of T(g).
AB  - Milling is a usual process used in the course of drug formulation, which however
      may change the physical nature of the end product. The diversity of the
      transformations of organic compounds upon milling has been widely demonstrated in
      the pharmaceutical literature. However, no effort has still been devoted to study
      the correlation between the nature of the transformation and the milling
      conditions. Results clarifying such transformations are shortly reviewed with
      special attention paid to the temperature of milling. The importance of the
      position of the glass transition temperature compared with that of milling is
      demonstrated. It is shown that decreasing the milling temperature leads to an
      increase of the amorphization tendency whereas milling above T(g) can produce a
      crystal-to-crystal transformation between polymorphic varieties. These
      observations contradict the usual suggestion that milling transforms the physical
      state only by a heating effect which induces a local melting. Equilibrium
      thermodynamics does not seem appropriate for describing the process. The driven
      alloys concept offers a more rational framework to interpret the effect of the
      milling temperature. Other results are also presented, which demonstrate the
      possibility for milling to form low temperature solid-state alloys that offer new
      promising ways to stabilize amorphous molecular solids.

PMID- 17455354
TI  - Structural study of polymorphs and solvates of finasteride.
AB  - NMR and XRD data are reported for several new forms of finasteride, including the
      results of complete structure determinations for three solvates. Form III of
      finasteride, hitherto only mentioned in the patent literature, and a new
      anhydrous form designated Form X, have been found in mixtures of polymorphs and
      their (13)C NMR chemical shifts obtained. The results demonstrate that the
      crystallographic asymmetric units contain three molecules and one molecule,
      respectively. Attempts to reproduce "Form H1", as described in a patent, resulted
      in a new IPA solvate hydrate. The previously-reported acetic acid, dioxane, and
      ethyl acetate solvates have been further characterised, and new THF and diethyl
      ether solvates prepared and characterised. The crystal structures of the dioxane,
      IPA, and THF solvates have been determined by single-crystal X-ray diffraction.
      All the solvates (except the acetic acid case) are found to be hemihydrates, to
      have a finasteride: solvent molar ratio of 2:1 and to have a common structure.
      The solvate molecules are highly disordered and sited in channels in the
      structure. The powder XRD patterns are characteristic of the common structure.
      These solvates may be distinguished by the characteristic CPMAS (13)C signals
      from the solvent molecules, but the resonances of the host finasteride structures
      differ only marginally, and powder XRD patterns are almost indistinguishable.
      Magic-angle spinning (MAS) proton spectra give sharp lines for the solvent peaks,
      confirming their high degree of mobility. This is further shown in one case by
      direct polarisation (13)C spectra. Mobility of the tert-butyl group is also
      implied. Thermal characteristics have been studied and TGA used (in conjunction
      with solution-state proton NMR) to estimate molar ratios.

PMID- 17455355
TI  - Correlations between molecular mobility and chemical stability during storage of
      amorphous pharmaceuticals.
AB  - Recent studies have demonstrated that molecular mobility is an important factor
      affecting the chemical stability of amorphous pharmaceuticals, including small
      molecular-weight drugs, peptides and proteins. However, quantitative correlations
      between molecular mobility and chemical stability have not yet been elucidated.
      The purpose of this article is to review literature describing the effect of
      molecular mobility on chemical stability during storage of amorphous
      pharmaceuticals, and to seek a better understanding of the relative significance
      of molecular mobility and other factors for chemical reactivity. We first
      consider the feature of chemical stability often observed for amorphous
      pharmaceuticals; changes in temperature dependence of chemical stability around
      matrix glass transition temperature (Tg), and greater stability associated with
      higher Tg. Secondly, we review papers which quantitatively studied the effects of
      the global mobility (often referred to as structural relaxation or -relaxation)
      of amorphous pharmaceuticals on chemical stability, and discuss correlations
      between chemical stability and global mobility using various equations that have
      thus far been proposed. Thirdly, the significance of local mobility of drug and
      excipient molecules in chemical reactivity is discussed in comparison with that
      of global mobility. Furthermore, we review literature reports which show no
      relationship between chemical stability and molecular mobility. The lack of
      apparent relationship is discussed in terms of the effects of the contribution of
      excipient molecules as reactants, the specific effects of water molecules, the
      heterogeneity of the matrix, and so on. The following summary has been obtained;
      the chemical stability of amorphous pharmaceuticals is affected by global
      mobility and/or local mobility, depending on the length scale of molecular
      mobility responsible for the chemical reactivity. In some cases, when activation
      energy for degradation processes is high and when other factors such as the
      specific effects of water and/or excipients contribute the degradation rate,
      stability seems to be largely independent of molecular mobility.

PMID- 17455356
TI  - Efficient co-crystal screening using solution-mediated phase transformation.
AB  - We have extended the established physical stability treatment for
      hydrates/solvates to co-crystals with solid co-crystal formers. Based on the
      proposed treatment, a suspension/slurry screening technique is developed and
      tested in sixteen pharmaceutical co-crystal systems with success. The theoretical
      treatment and the practical screening technique should benefit the researchers in
      the field of co-crystallization in improving the screening efficiency.

PMID- 17455357
TI  - Relationships between structural and thermal properties of anhydrous and solvated
      crystalline forms of brodimoprim.
AB  - The isolation and physicochemical characterization of four crystalline
      modifications of brodimoprim (5-[(4-bromo-3,5-dimethoxyphenyl)methyl]-2,4
      pyrimidinediamine, hereinafter BMP), a structural analog of trimethoprim (TMP),
      are reported. These phases include an unsolvated form of BMP, a hemihydrate (BMP
      0.5H(2)O), a 1:1 solvate containing isopropanol (BMP C(3)H(7)OH(iso)), and a
      hemichloroformate (BMP 0.5CHCl(3)). Unsolvated BMP was isolated both by
      recrystallization from a range of common solvents as well as by thermal
      decomposition of the above solvates and no evidence for polymorphism was found.
      PXRD data indicated that the three solvates crystallize in different
      arrangements. Data from thermal analysis (thermogravimetry (TGA), hot stage
      microscopy (HSM), differential scanning calorimetry (DSC)) of the solvates
      containing water and iso-propanol were interpreted on the basis of their single
      crystal X-ray structures which revealed that the modes of solvent inclusion in
      BMP 0.5H(2)O and BMP C(3)H(7)OH(iso) may be described as 'isolated site' and
      'lattice channel' type inclusions, respectively.

PMID- 17455358
TI  - Probing pseudopolymorphic transitions in pharmaceutical solids using Raman
      spectroscopy: hydration and dehydration of theophylline.
AB  - Theophylline is known to undergo vapor phase induced hydrate-anhydrate
      pseudopolymorphic transformations, which can affect its bioavailability. In this
      work, the kinetics of the pseudopolymorphic transitions of theophylline crystals
      in different storage conditions is studied using a vibrational spectroscopic
      technique. While the hydration is a single-step process with a half-life time of
      ca. 5 h, the dehydration occurs through a two-step mechanism. In addition, the
      phase stability of hydrate-anhydrate systems in different relative humidity (RH)
      conditions was probed. The critical RH for anhydrous teophylline was found to be
      at ca. 79%, while the critical RH for dehydration is ca. 30%.

PMID- 17455359
TI  - Process analytical technology: chemometric analysis of Raman and near infra-red
      spectroscopic data for predicting physical properties of extended release matrix
      tablets.
AB  - The purpose of this work was to develop a correlation between pharmaceutical
      properties such as hardness, porosity, and content with prediction models
      employed using Raman and near infra-red (NIR) spectroscopic methods. Metoprolol
      tartrate tablets were prepared by direct compression and wet granulation methods.
      NIR spectroscopy and chemical imaging, and Raman spectra were collected, and
      hardness, porosity, and dissolution were measured. The NIR PLS model showed a
      validated correlation coefficient of >0.90 for the predicted versus measured
      porosity, hardness, and amount of drug with raw and second derivative NIR
      spectra. Raman spectra correlated porosity of the tablets using raw data for
      directly compressed tablets and wet granulated tablets (r(2) > 0.90). A very
      close root-mean square error of calibration (RMSEC) and root-mean square error of
      prediction (RMSEP) values were found in all the cases indicating validity of the
      calibration models. Raman spectroscopy was used for the first time to predict
      physical quality attribute such as porosity successfully. Chemical imaging
      utilizing NIR detector also demonstrated to show physical changes due to
      compression differences. In conclusion, sensor technologies can be potentially
      used to predict physical parameters of the matrix tablets.

PMID- 17455360
TI  - Mechanistic study of the effect of roller compaction and lubricant on tablet
      mechanical strength.
AB  - Heckel analysis, tablet tensile strength, and indentation hardness were
      determined for a series of sieved and roller compacted microcrystalline cellulose
      mixtures under both unlubricated and lubricated conditions with magnesium
      stearate. These results have been used to evaluate the loss of reworkability
      following roller compaction for microcrystalline cellulose and show the extent of
      impact on tableting properties when magnesium stearate is added intragranularly
      prior to roller compaction. While results consistent with traditional work
      hardening are observed as shown by a modest increase in dynamic hardness and mean
      yield pressure for unlubricated, roller compacted microcrystalline cellulose, it
      is overshadowed by the overlubrication effect seen during roller compaction and
      in particular, the subsequent milling step. The common practice of lubricating
      the feedstock with magnesium stearate to avoid sticking of the material to the
      compaction rolls appears to be the major cause of decreased mechanical strength
      of the final compressed tablets.

PMID- 17455361
TI  - Characterization of prednisolone in controlled porosity osmotic pump pellets
      using solid-state NMR spectroscopy.
AB  - The overall objective of this study was to demonstrate the influence of
      formulation and processing variables on the physical state of prednisolone (PDL)
      in formulations consisting of PDL, microcrystalline cellulose (MCC), and
      sulfobutylether-beta-cyclodextrin (CD). PDL was used as a model drug in
      controlled porosity osmotic pump pellet (CP-OPP) formulations, and was
      characterized using solid-state NMR spectroscopy and other complimentary
      analytical techniques. Dosage forms and the solid-state properties of drugs and
      excipients in a formulation may be influenced by the processing conditions used.
      Several processing parameters, such as amount of water used in wet granulation
      and subsequent drying conditions, were found to affect the solid-state
      transformation of PDL. In addition, the presence of excipients in the CP-OPP was
      observed to decrease the degree of PDL crystallinity, presumably by creating an
      inclusion complex with the CD. A hydrated form of PDL was created when PDL was
      ground with water alone; however, this form was not observed in formulated
      products. Solid-state NMR spectroscopy was shown to be a powerful technique for
      the analysis of drug formulations and investigations of the effects of processing
      conditions.

PMID- 17455362
TI  - The influence of mechanical processing of dry powder inhaler carriers on drug
      aerosolization performance.
AB  - The influence of processing on the performance of carrier material used in dry
      powder inhalers was investigated. alpha-Lactose monohydrate crystals were
      processed by ball milling for cumulative time durations and their properties
      evaluated. As expected, milling reduced the median particle diameter while
      increasing fine particulate (<10 microm) and amorphous levels. Recrystallization
      of these partially amorphous samples resulted in a reduction in fines,
      elimination of amorphous material with little change in median diameter. To study
      the effects of processing on aerosolization performance, blends of lactose
      monohydrate with a model drug (nedocromil sodium trihydrate), were evaluated
      using an in vitro multistage liquid impinger (MSLI) model. In general, milling
      and storage of the carriers at high humidity (prior to blending) had a
      significant (ANOVA, p < 0.05) effect on the fine particle fractions (FPF; <6.8
      microm). These effects were attributed predominantly to the fines content,
      showing a strong correlation between increased fines and FPF (R(2) = 0.974 and
      0.982 for milled and recrystallized samples, respectively). However, this
      relationship only existed up to 15% fines concentration, after which agglomerate
      carrier segregation was observed and FPF decreased significantly. These results
      suggest that, after processing, high-dose drug formulation performance is
      dominated by the presence of fines.

PMID- 17455363
TI  - Structure and drug release in a crosslinked poly(ethylene oxide) hydrogel.
AB  - Hydrogels are a continuously expanding class of pharmaceutical polymers designed
      for sustained or controlled drug release. The structure and intermolecular
      interactions in such systems define their macroscopic properties. The aim of this
      study was to investigate the mechanism of swelling, drug impregnation, and drug
      release from poly(ethylene oxide) (PEO) gel crosslinked by urethane bonds. A
      combination of SAXS/WAXS/SANS techniques enabled us to determine the phase
      transition between lamellar and extended gel network, and to apply different
      descriptions of crystallinity, based on lamellar and crystal lattice structures.
      It is shown that even low (1-7% w/w) loading of model drugs acetaminophen and
      caffeine, produced significant disorder in the polymer matrix. This effect was
      particularly pronounced for acetaminophen due to its specific ability to form
      complexes with PEO. The drug-release profiles were analyzed using a general cubic
      equation, proposed for this work, which allowed us to determine the gel hydration
      velocity. The results indicate that the release profiles correlate inversely with
      the polymer crystallinity.

PMID- 17455364
TI  - Physical characterization of component particles included in dry powder inhalers.
      II. Dynamic characteristics.
AB  - Characteristics of particles included in dry powder inhalers is extended from our
      previous report (in this journal) to include properties related to their dynamic
      performance. The performance of dry powder aerosols for pulmonary delivery is
      known to depend on fluidization and dispersion which reflects particle
      interactions in static powder beds. Since the solid state, surface/interfacial
      chemistry and static bulk properties were assessed previously, it remains to
      describe dynamic performance with a view to interpreting the integrated database.
      These studies result in complex data matrices from which correlations between
      specific properties and performance may be deduced. Lactose particles were
      characterized in terms of their dynamic flow, powder and aerosol electrostatics,
      and aerodynamic performance with respect to albuterol aerosol dispersion. There
      were clear correlations between flow properties and aerosol dispersion that would
      allow selection of lactose particles for formulation. Moreover, these properties
      can be related to data reported earlier on the morphological and surface
      properties of the carrier lactose particles. The proposed series of analytical
      approaches to the evaluation of powders for inclusion in aerosol products has
      merit and may be the basis for screening and ultimately predicting particle
      performance with a view to formulation optimization.

PMID- 17455365
TI  - Neural basis of processing sequential and hierarchical syntactic structures.
AB  - The psychological processes through which humans learn a language have gained
      considerable interest over the past years. It has been previously suggested that
      language acquisition partly relies on a rule-based mechanism that is mediated by
      the frontal cortex. Interestingly, the actual structure involved within the
      frontal cortex varies with the kind of rules being processed. By means of
      functional MRI we investigated the neural underpinnings of rule-based language
      processing using an artificial language that allows direct comparisons between
      local phrase structure dependencies and hierarchically structured long-distance
      dependencies. Activation in the left ventral premotor cortex (PMC) was related to
      the local character of rule change, whereas long-distance dependencies activated
      the opercular part of the inferior frontal gyrus (Broca's area (BA) 44). These
      results suggest that the brain's involvement in syntactic processing is
      determined by the type of rule used, with BA 44/45 playing an important role
      during language processing when long-distance dependencies are processed. In
      contrast, the ventral PMC seems to subserve the processing of local dependencies.
      In addition, hippocampal activity was observed for local dependencies, indicating
      that the processing of such dependencies may be mediated by a second mechanism.

PMID- 17455367
TI  - Implementation of divide-and-conquer method including Hartree-Fock exchange
      interaction.
AB  - The divide-and-conquer (DC) method, which is one of the linear-scaling methods
      avoiding explicit diagonalization of the Fock matrix, has been applied mainly to
      pure density functional theory (DFT) or semiempirical molecular orbital
      calculations so far. The present study applies the DC method to such calculations
      including the Hartree-Fock (HF) exchange terms as the HF and hybrid HF/DFT.
      Reliability of the DC-HF and DC-hybrid HF/DFT is found to be strongly dependent
      on the cut-off radius, which defines the localization region in the DC formalism.
      This dependence on the cut-off radius is assessed from various points of view:
      that is, total energy, energy components, local energies, and density of states.
      Additionally, to accelerate the self-consistent field convergence in DC
      calculations, a new convergence technique is proposed.

PMID- 17455368
TI  - Electron affinities of heavier phosphoryl and thiophosphoryl halides APX3 (A = O,
      S and X = Br, I).
AB  - We carried out computational studies of OPX3 and SPX3 (X = Br and I) molecules
      and their corresponding anions using density functional theory, Moller-Plesset,
      and CCSD(T) methods with newly developed model core potentials (MCP).
      Reliabilities of the MCP were demonstrated by comparing experimental and
      calculated results. We computed the geometric structure, electron affinities, and
      electrostatic moments using systematic sequences of the dzp-, tzp-, and qzp
      quality basis sets. Both C3v and Cs symmetries were assumed to ascertain that
      minima on the potential energy surface were found. Infrared and Raman frequencies
      were calculated and compared with available experimental data. Natural population
      analyses were performed and used to determine distribution of the extra electron
      in anions.

PMID- 17455371
TI  - Computational methods in protein structure prediction.
AB  - This review presents the advances in protein structure prediction from the
      computational methods perspective. The approaches are classified into four major
      categories: comparative modeling, fold recognition, first principles methods that
      employ database information, and first principles methods without database
      information. Important advances along with current limitations and challenges are
      presented.

PMID- 17455375
TI  - Making it big in Taiwan.

PMID- 17455376
TI  - Satellite Symposium on Xenotransplantation.

PMID- 17455377
TI  - ICSC 2006. International conference on spatial cognition: dynamics in spatial
      interactions.

PMID- 17455378
TI  - Japan unveils 5-year plan to boost clinical research.

PMID- 17455379
TI  - NICE guidelines and the epilepsies: how should practice change? Authors' reply.

PMID- 17455380
TI  - Re: Surveillance colonoscopy in patients with colorectal cancer: how often should
      we be doing it? Surgeon 2006; 1: 3-5.

PMID- 17455381
TI  - Global. Military discharge over HIV outlawed in Mexico.

PMID- 17455382
TI  - U.S. government's funding restrictions for prostitution upheld.

PMID- 17455383
TI  - Sharing environmental health practice in the North American Arctic: a focus on
      water and wastewater service.
AB  - While providing water and wastewater services in rural Alaska has traditionally
      been difficult, the task has become even more challenging in the new millennium.
      A combination of factors has increased the cost and complexity of water and
      wastewater systems while leaving residents with diminished ability to pay for
      services. Alaskans may be better able to meet these challenges by learning more
      about and adopting some approaches used in similar regions. In March 2005, the
      author visited six communities in the Canadian Northwest Territories (NWT). Made
      possible by NEHA's Sabbatical Exchange Ambassador Award, these visits provided
      the author an opportunity to learn about the NWT approach to providing water and
      wastewater services. He then compiled comprehensive descriptions of each region's
      service delivery model. Comparisons were made, and features of interest were
      identified and used to develop recommendations for improving service delivery in
      rural Alaska.

PMID- 17455384
TI  - [The 80th general meeting of the Japanese Leprosy Association. Yokohama, Japan.
      May 17-19, 2007. Abstracts].

PMID- 17455385
TI  - [The 77th annual meeting of the Japanese Society for Hygiene. Osaka, Japan. March
      25-28, 2007. Abstracts].

PMID- 17455386
TI  - The stubborn scale. Getting off a weight-loss plateau.

PMID- 17455387
TI  - Microbiology devices; reclassification of herpes simplex virus types 1 and 2
      serological assays. Final rule.
AB  - The Food and Drug Administration (FDA) is reclassifying herpes simplex virus
      (HSV) types 1 and/or 2 (HSV 1 and 2) serological assays from class III (premarket
      approval) to class II (special controls). FDA had earlier proposed this
      reclassification on its own initiative based on new information. Elsewhere in
      this issue of the Federal Register, FDA is announcing the availability of a class
      II special controls guidance entitled "Class II Special Controls Guidance
      Document: Herpes Simplex Virus Types 1 and 2 Serological Assays."

PMID- 17455388
TI  - Temporary extension of attorney fee payment system to Title XVI; 5-year
      demonstration project extending fee withholding and payment procedures to
      eligible non-attorney representatives; definition of past-due benefits; and
      assessment for fee payment services. Interim final rules with request for
      comments.
AB  - We are issuing these interim final rules to reflect in our regulations three self
      implementing statutory provisions in the Social Security Protection Act of 2004
      (SSPA) and three related self-implementing provisions in earlier legislation.
      These earlier provisions are in the Omnibus Budget Reconciliation Act of 1990
      (OBRA), the Social Security Independence and Program Improvements Act of 1994
      (SSIPIA), and the Ticket to Work and Work Incentives Improvement Act of 1999
      (TWWIIA).

PMID- 17455389
TI  - Neretva Valley: from leprosarium to nature park.

PMID- 17455390
TI  - [On the technique for intravitreal injections].

PMID- 17455391
TI  - Dosimetric characterization of the irradiation cavity for accelerator-based in
      vivo neutron activation analysis.
AB  - A neutron irradiation cavity for in vivo activation analysis has been
      characterized to estimate its dosimetric specifications. The cavity is defined to
      confine irradiation to the hand and modifies the neutron spectrum produced by a
      low energy accelerator neutron source to optimize activation per dose. Neutron
      and gamma-ray dose rates were measured with the microdosimetric technique using a
      tissue-equivalent proportional counter at the hand irradiation site and inside
      the hand access hole. For the outside of the cavity, a spherical neutron dose
      equivalent meter and a Farmer dosemeter were employed instead due to the low
      intensity of the radiation field. The maximum dose equivalent rate at the outside
      of the cavity was 2.94 microSv/100 microA min, which is lower by a factor of
      1/2260 than the dose rate at the hand irradiation position. The local dose
      contributions from a hand, an arm and the rest of a body to the effective dose
      rate were estimated to be 1.73, 0.782 and 2.94 microSv/100 microA min,
      respectively. For the standard irradiation protocol of the in vivo hand
      activation, 300 microA min, an effective dose of 16.3 microSv would be delivered.

PMID- 17455392
TI  - Three-dimensional ultrasonography.

PMID- 17455393
TI  - [Doppler ultrasound imaging in ophthalmology].

PMID- 17455394
TI  - [Sensitivity to glare and its clinical significance].

PMID- 17455395
TI  - [Knight's jousting tournaments and eye injuries].

PMID- 17455396
TI  - We know much about what to do but little about how to do it: experiences with a
      weekly multimicronutrient supplementation campaign.
AB  - BACKGROUND: Global population growth is concentrated in urban areas, but there is
      little understanding of how to implement the necessary interventions to control
      food and nutrition insecurity. In the urban area of Peru, food insecurity is
      characterized mainly by micronutrient deficiencies and not by energy deficiency.
      OBJECTIVE: To increase the effectiveness and cost-effectiveness of weekly
      multimicronutrient supplementation programs in poor urban communities. METHODS: A
      series of operational studies were conducted of preventive weekly
      multimicronutrient supplementation to reduce micronutrient-deficiency anemia in a
      population consisting of 8,081 children under 5 years of age and 20,082 women and
      adolescent girls of reproductive age (12 through 44 years). RESULTS: This is one
      of a series of papers that describe in as much detail as possible the experiences
      of a multimicronutrient intervention program for poor urban mothers and their
      young children and summarizes the lessons learned for consideration of future
      programming. CONCLUSIONS: This paper shows that such programs can achieve a high
      compliance with good training of program staff involvement of the community,
      education and motivation of beneficiaries, adequate supplies, and careful
      monitoring.

PMID- 17455397
TI  - Baseline evaluation of nutritional status and government feeding programs in
      Chiclayo, Peru.
AB  - BACKGROUND: Because of the rapid growth of the urban population in Peru, food and
      nutrition insecurity will occur increasingly in this population. For appropriate
      policy setting and programming, the food and nutrition situation of the urban
      poor requires better understanding. OBJECTIVE: To gain information about the
      nature, magnitude, severity, and causes of the nutritional problems of the
      population in low-income areas of the city of Chiclayo, Peru. METHODS: A cross
      sectional nutrition survey was conducted in 1,604 households, covering children
      under 5 years of age and their parents. RESULTS: The prevalence rates of
      stunting, wasting, overweight. and anemia in children were 15.4%, 1.3%, 4.6%, and
      65.7%, respectively; one third of adults were overweight, and one tenth were
      obese; 2.1% of the mothers were underweight; and 34.3% of mothers and 12.2% of
      fathers had anemia. Governmental feeding programs did not address these problems
      adequately. CONCLUSIONS: Interventions must have adequate targeting; address
      appropriate responses at the household, community, and national levels; and
      reduce stunting, obesity, and iron-deficiency anemia.

PMID- 17455398
TI  - Effectiveness of distribution of multimicronutrient supplements in children and
      in women and adolescent girls of childbearing age in Chiclayo, Peru.
AB  - BACKGROUND: There is a need to better understand the coverage of scaled-up
      multimicronutrient supplementation programs. OBJECTIVE: The coverage of the
      distribution of multimicronutrient supplements in 26 urban communities among
      women and adolescent girls 12 through 44 years of age and children under 5 years
      of age was evaluated for purposes of scaling-up. METHODS: Formative research and
      descriptive statistics were used to analyze the distribution of supplements.
      RESULTS: Despite a delayed memorandum of understanding with the health sector and
      delayed delivery by the producer of the supplement, a high coverage rate of
      supplement distribution to the children (88% on average during the 3 months of
      supplementation) was still achieved as a result of the strong commitment of the
      community and the Integrated Food Security Program. The lower coverage rate among
      women and adolescent girls (47% on average) was the result of too short a period
      of enrollment in the program. There was no decrease of coverage during the 3
      months of supplementation in both groups. CONCLUSIONS: Effective, sustainable,
      large-scale micronutrient supplementation programs require broad partnerships
      with commitments of governmental and nongovernmental organizations, communities,
      and the private sector. Availability of the supplements and communication
      materials must be secured well ahead of the supplementation campaign and
      distribution of the supplement.

PMID- 17455399
TI  - Effectiveness of the communication program on compliance in a weekly
      multimicronutrient supplementation program in Chiclayo, Peru.
AB  - BACKGROUND: Compliance with daily micronutrient supplementation is usually poor
      and the question arises whether compliance with a weekly regimen would be better.
      OBJECTIVES: The inputs (messages and channels), output (increase of knowledge),
      and outcome (behavior changes) ofa communication campaign in a micronutrient
      supplementation program for women and adolescent girls 12 through 44 years of age
      and children under 5 years of age (primary audience) were analyzed. METHODS: The
      communication program addressed not only the primary, but also the secondary
      (facilitators) and tertiary audiences. Formative research and descriptive
      statistics were used to analyze the communication campaign. RESULTS: Nearly all
      women and adolescent girls (89%) and children (91%) took at least 75% of the
      supplements over the 3-month period. The incidence rates of reported negative
      side effects of supplementation in children and in women and adolescent girls
      were less than 10%. Knowledge of micronutrient nutrition among facilitators of
      all ages and education levels increased significantly (p <.001). CONCLUSION: . A
      thoroughly planned and implemented nutrition communication program can secure
      high compliance of the beneficiaries of micronutrient supplementation programs.
      The necessary supplies should be available at least 3 months before program
      implementation. With an adequate communication program, supplementation programs
      can be used to foster food-based approaches for the target audience.

PMID- 17455400
TI  - Protective effect of multimicronutrient supplementation against anemia among
      children, women, and adolescent girls in lower-income areas of Chiclayo, Peru.
AB  - BACKGROUND: The Integrated Food Security Program (Programa Integrado de Seguridad
      Alimentaria [PISA]) implemented a campaign to promote weekly multimicronutrient
      supplementation among women and adolescent girls of childbearing age and children
      under 5 years of age. OBJECTIVES: To assess the impact of the campaign on the
      growth of children and on anemia among children and among women and adolescent
      girls of childbearing age. METHODS: Weekly multimicronutrient supplementation was
      provided for 8 weeks. Weights, heights, and hemoglobin concentrations were
      assessed at the beginning and end of the campaign. RESULTS AND CONCLUSIONS:
      Although supplementation did not significantly increase the hemoglobin
      concentrations of children (p = .80) or women and adolescent girls (p = .65) in
      the intervention group, the hemoglobin concentrations of the comparison groups
      were significantly lower after 8 weeks (p = .001 for children and p = .03 for
      women and adolescent girls). Furthermore, the percentage of anemic children in
      the comparison group increased significantly (p <.001), and the final value was
      significantly higher than that for the intervention group (p = .004). There were
      no significant effects of weekly multimicronutrient supplementation on the growth
      of children, but the study was too short to reliably determine any effects on
      growth.

PMID- 17455401
TI  - Costs of the multimicronutrient supplementation program in Chiclayo, Peru.
AB  - BACKGROUND: There is little information on the cost parameters of weekly
      multimicronutrient supplementation programs. OBJECTIVE: To assess the cost
      parameters and cost-effectiveness of a weekly multimicronutrient supplementation
      program in an urban population of Peru. METHODS: Data from the Integrated Food
      Security Program (Programa Integrado de Seguridad Alimentaria [PISA]), which
      distributed capsules and foodlets to women and adolescent girls and to children
      under five, were extrapolated to a population of 100,000 inhabitants. RESULTS:
      The annual cost per community member was US$1.51. The cost-effectiveness ratio
      was US$0.12 per 1% of prevented anemia per community member. CONCLUSIONS: These
      costs are in the upper margin of iron supplementation alone. They will decrease
      notably when weekly multimicronutrient supplementation programs are integrated
      into health packages and participation by women increases. Focusing on
      micronutrient deficiencies would prevent these problems, and food-distribution
      programs would be effectively targeted to food-deficient populations.

PMID- 17455402
TI  - Lessons learned from the scaling-up of a weekly multimicronutrient
      supplementation program in the integrated food security program (PISA).
AB  - BACKGROUND: Weekly multimicronutrient supplementation was initiated as an
      appropriate intervention to protect poor urban populations from anemia.
      OBJECTIVE: To identify the lessons learned from the Integrated Food Security
      Program (Programa Integrado de Seguridad Alimentaria [PISA]) weekly
      multimicronutrient supplementation program implemented in poor urban populations
      of Chiclayo, Peru. METHODS: Data were collected from a 12-week program in which
      multimicronutrient supplements were provided weekly to women and adolescent girls
      12 through 44 years of age and children under 5 years of age. A baseline survey
      was first conducted. Within the weekly multimicronutrient supplementation
      program, information was collected on supplement distribution, compliance,
      biological effectiveness, and cost. RESULTS: Supplementation, fortification, and
      dietary strategies can be integrated synergistically within a micronutrient
      intervention program. CONCLUSIONS: To ensure high cost-effectiveness of a weekly
      multimicronutrient supplementation program, the following conditions need to be
      met: the program should be implemented twice a year for 4 months; the program
      should be simultaneously implemented at the household (micro), community (meso),
      and national (macro) levels; there should be governmental participation from
      health and other sectors; and there should be community and private sector
      participation. Weekly multimicronutrient supplementation programs are cost
      effective options in urban areas with populations at low risk of energy
      deficiency and high risk of micronutrient deficiencies.

PMID- 17455404
TI  - Pathophysiology of congenital heart diseases.

PMID- 17455403
TI  - IT empowered anaesthesiologist.

PMID- 17455405
TI  - Efficacy of combined modified and conventional ultrafiltration during cardiac
      surgery in children.
AB  - Thirty children undergoing cardiac surgery under cardiopulmonary bypass (CPB)
      were prospectively studied to assess beneficial effects of modified
      ultrafiltration (MUF) over and above conventional ultrafiltration (CUF).
      Transoesophaegeal echocardiography determined ejection fraction (EF), fractional
      area change (FAC) and posterior wall thickness in end-diastole and end-systole
      were measured and compared in two groups undergoing CUF (group I) and CUF plus
      MUF (group II). Haemodynamic data, haematocrit, temperature drift, postoperative
      chest tube drainage in first 48 hours, ventilation and intensive care unit (ICU)
      stay were also recorded. Within group data were analysed by general linear trend
      and intergroup comparisons were made with t-test. EF and FAC decreased at 0 min
      after CPB in both groups, but both recovered at 10 and 30 min after CPB in group
      II. Increase in EF and FAC in group II was about 12-15 % and 3-5 % from 0 min
      respectively. There was also significant improvement in posterior wall thickness
      and haematocrit (P<0.05) in group II. Patients in group II maintained better
      systolic blood pressure and heamoglobin after CPB. Chest tube drainage in first
      48 hours was significantly less in group 1I (100 -18 verses 85 +/-20 ml, P<0.05),
      but ventilation and ICU stay were not different between the two groups. Combined
      ultrafiltration has beneficial effect an haemodynamics with improvement in EF and
      FAC. It improves haematocrit and decreases chest pulse drainage.

PMID- 17455406
TI  - Treating metabolic impairment and myocardial stunning with phosphodiesterase
      inhibitor type III, milrinone, administered prior to coronary artery occlusion in
      the presence of calcium channel blockade in pigs.
AB  - This study examined milrinone effects on ischaemic myocardial metabolism and
      function with calcium blockade. We studied 15 pigs in 3 groups: group C received
      no drugs; group D received diltiazem 5 mg bolus followed by infusion; group D+M
      received diltiazem and milrinone (50microg/Kg). The left anterior descending
      (LAD) artery was then occluded for 15 minutes. Left ventricular (LV) function
      data obtained included rate, pressures, output, Emax, and dP/dT. Blood lactate
      was obtained from the LAD and circumflex vessels at baseline, end of occlusion,
      early (15 min) and late (1 hour) reperfusion. In group D+M, less depression of LV
      function occurred during ischaemia and early reperfusion. Lactate extraction in
      the LAD region was less negative in D+M group than in the group without milrinone
      during ischaemia and late reperfusion. We conclude the preemptive administration
      of milrinone prior to ischaemia added to calcium blockade improved
      myocardialfunction and ischaemic metabolic effects.

PMID- 17455407
TI  - Comparison of analgesic efficacy of fentanyl and sufentanil for chest tube
      removal after cardiac surgery.
AB  - Chest tube removal in the postcardiac surgical patients is a painful and
      distressful event. Fentanyl and sufentanil have not been used for pain control
      during chest tube removal in the postoperative period. We compared efficacy
      offentanyl and sufentanil in controlling pain due to chest tube removal. One
      hundred and forty one adult patients undergoing cardiac surgery were recruited in
      a prospective, randomized, double blind, placebo controlled study. Patients were
      randomized to receive either 2 microg/Kg fentanyl IV or 0.2 microg/Kg sufentanil
      IV or 2 ml isotonic normal saline, 10 min before removing chest tubes. Pain
      intensity was assessed by measuring visual analog scale pain score 10 minutes
      before removing chest tubes and 5 min and 20 min after removing chest tubes.
      Level of sedation, heart rate, arterial pressure, oxygen saturation, and
      respiratory rate were recorded by a blinded observer at the same time intervals.
      Mean pain intensity scores 10 minutes before removal of chest tubes infentanyl,
      sufentanil and control groups were 23.88+/-5.2, 25.10+/-5.39 and 23.64+/-6.10
      respectively. The pain scores 5 minutes after chest tube removal were reduced to
      20.11+/-6.9 (p<0.05) in the fentanyl group and 13.60+/-6.60 (p<0.05) in the
      sufentanil group, whereas in control group pain scores increased to 27.97+/-8.39
      (p<O.05). The pain scores in sufentanil group were significantly lower compared
      with fentanyl or control group. Sedation scores remained low in all groups and
      patients remained alert and none of the patients showed any adverse effects of
      opioids. Heart rate, arterial pressure and respiratory rate had least variations
      in sufentanil group than fentanyl or control group.

PMID- 17455408
TI  - Comparison of sevoflurane and isoflurane in OPCAB surgery.
AB  - Maintenance of anaesthesia with volatile anaesthetic agents affects the
      perioperative course of patients undergoing off-pump coronary artery bypass
      (OPCAB) surgery. This facilitates adequate depth of anaesthesia, reduction in
      need of analgesic dosage, early extubation and transfer from Intensive Care Unit.
      We compared two volatile anaesthetic agents sevoflurane and isoflurane in terms
      of haemodynamic effects, amount of analgesic needed during surgery, quantity of
      agent needed for maintenance of anaesthesia and postoperative recovery in 40
      patients undergoing OPCAB surgery. Anaesthesia was induced with fentanyl,
      midazolam and thiopentone, and vecuronium was used for muscle relaxation. An
      Octopus stabiliser was used and coronary anastomosis was performed using internal
      mammary artery and saphenous vein grafts. Routine monitoring was performed. The
      depth of anaesthesia was monitored using Bispectral index monitor. The
      inspired/expired concentration of anaesthetic agents to maintain the desired BIS
      and the amount of volatile anaesthetic agent needed was also noted. The amount of
      analgesic used intraoperatively was noted in both the groups. The 'time of
      awakening' defined as eye opening on verbal commands, and time of extubation were
      noted. There were no differences in haemodynamic parameters, depth of
      anaesthesia, and quantity of agent needed, but patients in isoflurane group
      required more intraoperative analgesics than sevoflurane group. Time of awakening
      (48+/-13 vs 114 +/- 21 mins; P < 0.001) and subsequent extubation (124 +/- 25 vs
      177 +/- 36 mins, P<0.001) was earlier in sevoflurane group than isoflurane group.
      There was no evidence of perioperative myocardial infarction in both the groups.
      We conclude that sevoflurane and isoflurane can both be safely used in OPCAB
      surgery, but the awakening and extubation times are significantly less with
      sevoflurane.

PMID- 17455409
TI  - Inhaled prostacyclin for the management of pneumonia in a patient with cyanotic
      heart disease with superior cavo-pulmonary connection.

PMID- 17455410
TI  - Off-pump coronary artery bypass grafting in a polycythaemic patient--case report
      and review of literature.

PMID- 17455411
TI  - Increased prothrombin time and lactic acidosis: rofecoxib drug interaction with
      acenocoumarin and metformin.

PMID- 17455412
TI  - Absent left main coronary artery.

PMID- 17455413
TI  - Choardae tendineae from posteromedial papillary muscle inserting into the
      anterior mitral leaflet--an unusual presentation.

PMID- 17455414
TI  - An unusual tracheal intubation in a patient with tracheo-oesophageal fistula.

PMID- 17455415
TI  - Anaesthesia for off-pump coronary artery surgery.

PMID- 17455416
TI  - XDR-TB--danger ahead.

PMID- 17455417
TI  - Management of multi-drug resistant tuberculosis: practitioner's view point.
AB  - Multi-Drug Resistant Tuberculosis (MDR-TB) is a growing hazard to human health
      world wide and threat to control of tuberculosis. Current estimates report the
      prevalence of primary and acquired MDR-TB in India as 3.4% and 25% respectively.
      MDR-TB is suspected if sputum is persistently +ve for AFB along with clinical and
      radiological deterioration after multiple courses of irregular or regular
      treatment including 4 months of WHO retreatmant regimens under direct observation
      . Diagnosis is confirmed by drug susceptibility testing from reliable and reputed
      laboratories under constant quality control. Reports of susceptibility should not
      be accepted uncritically. Treatment of MDR-TB should be at a specialized centre
      with standard microbiology laboratory facilities. Though treatment guidelines
      including standardized, empirical and individualized approaches have been laid
      down by the WHO but therapy should be tailored to the needs of the particular
      patient. Treatment of MDR-TB is difficult, complicated, much costlier,
      challenging and needs experience and skills. All measures should be taken to
      persuade and encourage patients not to stop treatment despite all its discomforts
      to prevent morbidity, mortality and transmission of MDR-TB. Current proposal of
      DOTS Plus by WHO highlights the comprehensive management strategy to control MDR
      TB. MDR-TB is a man-made problem and its emergence can be prevented by prompt
      diagnosis and effective treatment of all TB cases. Adoption of directly observed
      treatment short course (DOTS) to prevent the resistant/multi-drug resistant
      strains and careful introduction of second line drugs to treat patients with MDR
      TB are the top priorities for the proper control of MDR-TB.

PMID- 17455418
TI  - Status of re-registered patients for tuberculosis treatment under DOTS programme.
AB  - OBJECTIVE: To assess the proportion of patients re-registered after default,
      failure or successful treatment, completion and evaluate their treatment outcome.
      SETTING: Tuberculosis patients diagnosed were registered for treatment under DOTS
      in rural area, South India. Patients reregistered during 1999-2004 identified
      from the TB register were considered for analysis. RESULTS: Among 273 Category-I
      patients 'defaulted' 23% and among 112 'failure' cases 68% were re-registered.
      After 'successful treatment completion' of 1796 cases 6.5% were re-registered as
      relapse. Corresponding figures for Category II were 20% of 281 defaulters; 23% of
      60 failures; 12.9% of 302 'successful treatment completion' patients. Among
      patients re-registered as 'default', subsequent default was also high (57% vs
      37%). Failure in Category II treatment was similar among patients who were re
      registered for Category II and initially registered in it for treatment. Median
      delay for reregistration was >200 days for 'defaulters' and 18 days for
      'failures'. CONCLUSION: Our findings emphasise the need for continuing motivation
      and prompt defaulter retrieval action to reduce default at all stages of
      treatment. 'Defaulters' need to be contacted so that they can be started on
      treatment without delay. Patients declared as 'successful treatment completion'
      should be encouraged to report if chest symptoms recur.

PMID- 17455419
TI  - Social status makes a difference: tuberculosis scenario during National Family
      Health Survey-2.
AB  - BACKGROUND: The poorest people are vulnerable to Tuberculosis because of the
      living and working conditions but they plunge deeper into poverty as a
      consequence of this disease. AIMS: The present study focuses on the socio
      demographic characteristics of patients of TB with specific reference to
      prevalence of TB and health care seeking behaviour of men and women. METHODS: The
      data for the study comes from nation-wide National Family Health Survey -2,
      conducted in 1998-99. Paper looks at the relationship of reporting TB infection
      and seeking treatment for men and women by various socio-economic
      characteristics. Multivariate logistic regressions are applied to find the
      significant factors explaining reporting of TB and treatment-seeking. RESULTS: In
      the entire sample 1735 males and 1266 females are reported to suffer from TB.
      Reporting of TB is significantly (p=0.000) more among males having
      charecteristics with lower standard of living, scheduled tribes from rural area
      and illiterate population. It increases with age. Significant difference
      (p=0.002) is observed between urban and rural female's treatment seeking for TB.
      In case of females as age increases, treatment seeking goes down (p=0.007).
      Treatment seeking for currently married women is less frequent than that of all
      other women. CONCLUSIONS: Apart from economic status and living conditions, place
      of residence (urban / rural) and ethnic identity made people more vulnerable in
      terms of reporting the disease and access to treatment.

PMID- 17455420
TI  - Immunohistochemical localization of mycobacterium tuberculosis complex antigen
      with antibody to 38 kDa antigen versus Ziehl Neelsen staining in tissue
      granulomas of extrapulmonary tuberculosis.
AB  - BACKGROUND: Extra-pulmonary tuberculosis often presents a diagnostic challenge
      because of its diverse clinical manifestations and low yield of acid fast bacilli
      in tissue sections. AIM: The aim of the present study is immuno-histochemical
      localization of tuberculous bacilli or their components that persist in the
      granulomas but have lost the property of staining with acid fast stains and to
      assess the advantage of immuno-staining over conventional Ziehl Neelsen staining.
      MATERIAL AND METHODS: Immuno-histochemical staining using species-specific
      monoclonal anti-body to 38 kDa protein of Mycobacterium tuberculosis complex and
      Ziehl-Neelsen staining for acid fast bacilli (AFB) was done on 69; 36 cases of
      confirmed extra-pulmonary tuberculosis and 33 non-tuberculous cases, in archival
      formalin fixed paraffin embedded tissue sections OBERVATIONS: AFB positivity was
      observed in only 36.1% of tuberculous granulomas while immuno-histochemical
      staining was positive in 100% of tuberculous granulomata with zero false
      positivity and negativity. CONCLUSIONS: The immuno-hiostochemical localization of
      tuberculous bacilli and their components in tissue sections may be an efficient
      diagnostic adjunct to conventional ZN staining for the diagnosis of granulomas of
      extra-pulmonary tuberculosis. The technique is simple, sensitive and specific. It
      can be standardized and performed by trained technicians in routine laboratory.
      This will also help in clinical decision-making and in reducing the usual
      practice of prescribing empirical anti-tubercular treatment based on clinical
      suspicion alone in the absence of demonstrable evidence of tuberculous infection.

PMID- 17455421
TI  - Effective participation of TB sanatoria in Revised National TB Control Programme
      (DOTS) in a metropolitan city.
AB  - BACKGROUND: Revised National TB Control Programme has been implemented since 1998
      in Bangalore metropolitan city which has several big general hospitals, including
      two TB sanatoria which attract a large number of respiratory symptomatic and TB
      patients. Till recently there was significant loss of patients for follow up
      because of lack of mechanism to reach the patients, good recording practices and
      linkage with district TB control office. OBJECTIVE: To establish an effective
      referral mechanism between TB sanatoria and peripheral health institutions of the
      government for providing un-interrupted supervised treatment (DOT) to all newly
      detected TB patients. METHOD: TB sanatoria remain as "islands" when Reyised
      National TB Control Programme (RNTCP) with DOTS strategy is implemented. Damien
      Foundation India Trust (DFIT) provided a Technical Support Team (one medical
      consultant and three supervisors) to assist in implementation of RNTCP in the
      district. DFIT liaised with both partners and established procedures for
      recording correct address, informing health institutions and Senior TB
      Supervisors (STS) and monitoring referrals. Referral slip and a copy of treatment
      card were given to patients. One copy of treatment card was sent to respective
      health facility. Initially the number of STS was not adequate to follow up the
      patients. The supervisors of Technical Support Team ensured that they were
      treated in peripheral health institutions or near patients' residence. All STS
      were in position one year after initiation of this effort. RESULTS: The referral
      system is functional. Case holding improved from about 50% to 85% during 2002
      2005 by effective transfer through referrals. CONCLUSION: Interfacing of NGO
      between district TB control office and TB sanatoria enabled the establishment of
      effective collaboration. Initial reluctance was replaced by complete
      participation in the TB control programme.

PMID- 17455422
TI  - A study of phage based diagnostic technique for tuberculosis.
AB  - BACKGROUND: Tuberculosis (TB) is a leading infectious disease in India. Diagnosis
      of TB has always been a problem due to slow rate of growth of Mycobacterium
      tuberculosis. In this study we have compared the conventional tools for diagnosis
      of TB with the new Fast Plaque TB TM MATERIAL AND METHODS: Two hundred and twelve
      clinically suspected cases of TB were enrolled for the study. Three consecutive
      early morning sputum samples were collected from each patient. Sputum smears were
      examined after staining with ZN stain and the sputum samples were later subjected
      to culture and phage assay. RESULTS: It was seen from the study that out of the
      total 212 cases, 106 were phage positive and 106 were phage negative. Sensitivity
      of the phage test with respect to AFB smear is 94.34% and specificity of the
      phage test is 93.88%. A total of 120 specimens grew on LJ media, of which 112
      were Mycobacterium tuberculosis, 2 were Mycobacterium Kansasii, 4 were
      Mycobacterium avium complex and 2 grew Mycobacteriumfortuitum group. Out of these
      120 specimens which grew on LJ, 104 were also positive for phage assay. All the 8
      Non-Tubercular Mycobacteria were negative by the Fast Plaque Assay. Out of the 92
      which were negative on LJ, 2 were positive by phage assay. Sensitivity and
      specificity of phage assay with respect to growth on LJ was 92.86% and 97.83%
      respectively. CONCLUSION: The study showed that phage assay is a rapid, reliable
      and cost effective method in diagnosing pulmonary tuberculosis from clinical
      samples.

PMID- 17455423
TI  - Reverse passive haemagglutination (RPHA) test for detection of mycobacterial
      antigen in the cerebrospinal fluid for diagnosis of tubercular meningitis.
AB  - BACKGROUND: Various serological techniques have been developed to detect
      antibodies and antigens in the cerebrospinal fluid (CSF) for diagnosis of
      tubercular meningitis. Most of the serological assays are ELISA based. Attempts
      have been made to use much simpler antigen detection techniques like the reverse
      passive haemagglutination (RPHA)which is simple and cost-effective. AIMS: To
      evaluate the reverse passive haemagglutination (RPHA) test for detection of
      mycobacterial antigens in the CSF for diagnosis of tubercular meningitis.
      METHODS: In the present study, we have made the use of polyclonal antiserum
      against heat killed whole Mycobacterium tuberculosis bacilli to sensitize the
      RBCs in RPHA to detect antigens in clinically suspected cases. A total of 46
      cases (clinically suspected TBM 24, culture proven TBM 2, non- TBM cases 20) were
      included in the present study for detecting M. tuberculosis antigen in the CSF
      specimens. RESULTS: Of the 26 test CSF specimens, 13 CSF specimens were positive
      by RPHA while 4 of the 20 control CSF specimens were also reactive. Two culture
      positive specimens included in the study were positive by RPHA. Of the 4 control
      CSF specimens positive by RPHA, 3 were culture proven cases of pneumococcal
      meningitis and 1 was a case of cryptococcal meningitis. The RPHA is found to be
      50% sensitive and 80% specific; and showed a 76.4 % positive predictive value and
      a 55.2 % negative predictive value. CONCLUSION: The RPHA is a simple test that
      could be used as an adjunct in diagnosing TBM. It does not require any special
      equipment or technically trained or skilled manpower. It is economical and can be
      afforded for use in community where TBM is more prevalent. Even though the
      present study showed a poor sensitivity and specificity, further identification,
      characterization and evaluation of better immuno-dominant and specific antigens
      or epitopes, and the usage of antibodies developed against such mycobacterial
      antigens might improve the sensitivity and specificity of this test.

PMID- 17455424
TI  - Status report on RNTCP- 3Q 2006. Pursuing high quality DOTS services.

PMID- 17455425
TI  - Ulcerative lupus vulgaris of face: an uncommon presentation in India.
AB  - Tuberculosis affects the population world wide, more among those living in
      developing countries. The incidence of tuberculosis registered an upward trend
      even in developed countries, with the advent of HIV infection. Cutaneous
      tuberculosis accounts for about 1% of cases of extra-pulmonary tuberculosis.
      Cutaneous tuberculosis presents with various lesions ranging from ulcerative to
      proliferative or hyperkeratotic lesions. The lesions may sometimes be associated
      with marked destruction of the tissues resulting in marked disfigurement,
      especially when it involves face as seen in cases of Lupus Vulgaris. A case of
      Lupus Vulgaris in a young woman with extensive ulceration of face which responded
      to ATT resulting in scarring of the face is reported for its rarity amongst
      Indian population as against western population.

PMID- 17455426
TI  - The recent Karlsruhe Workshop for Early Career Prosthodontic Educators.

PMID- 17455427
TI  - Why are there so few female prosthodontic teachers?

PMID- 17455428
TI  - Partial neutralization of the acidogenic Western diet with potassium citrate
      increases bone mass in postmenopausal women with osteopenia. Interview by Nicola
      Zitzmann.

PMID- 17455429
TI  - Oral bisphosphonate therapy and osteonecrosis of the jaw: what to tell the
      concerned patient.
AB  - Bisphosphonate-associated osteonecrosis of the jaw (BONJ) is encountered
      predominantly in cancer populations being treated with high-dose intravenous
      bisphosphonates for skeletal complications such as bone metastases and secondary
      fracture risk. A minority of BONJ lesions have been observed in patients
      receiving oral bisphosphonates for management of osteoporosis or osteopenia. In
      this paper, the current knowledge pertaining to the incidence, definition, and
      signs and symptoms of BONJ is presented, followed by a discussion of the
      incidence and consequences of osteoporotic skeletal fracture and the use of oral
      bisphosphonates to mitigate fracture. The risk of BONJ appears to be very small
      in patients taking oral bisphosphonates. In addition, the consequences of
      osteoporotic fracture likely have significantly greater mortality and morbidity
      than BONJ. Within this context, management concepts and guidelines are presented
      to help the dental clinician allay concerns about BONJ expressed by patients
      receiving oral bisphosphonate therapy.

PMID- 17455430
TI  - Microleakage in full-crown all-ceramic restorations: influence of internal
      surface treatment, silane application, alumina system, and substrate.
AB  - This study investigated the influence of internal surface treatment and margin
      location on the microleakage of 2 alumina-reinforced ceramic crown systems: In
      Ceram (VITA Zahnfabrik) and Procera (Nobel Biocare). Full crowns were produced
      for each of the 2 systems (n = 24) in human premolars, with margins located in
      enamel and dentin, and luted with Single Bond and RelyX ARC (3M ESPE). Four
      internal ceramic treatments were tested: (1) aluminum oxide blasting (AO), (2) AO
      plus silane, (3) hydrofluoric acid etching (HF), and (4) HF plus silane. After
      thermal cycling, leakage was measured quantitatively. Statistical analysis (P <
      .05) showed higher leakage in dentin margins compared to enamel. In enamel,
      Procera showed greater leakage compared to In-Ceram. Generally, lower
      microleakage was observed for the AO plus silane treatment.

PMID- 17455431
TI  - A comparison of the accuracy of fit of 2 methods for fabricating implant
      prosthodontic frameworks.
AB  - PURPOSE: To compare the in vitro 3-dimensional (3D) accuracy of fit of laser
      scanned Computer Numeric Controlled (CNC)-milled implant titanium frameworks to
      that of conventional cast frameworks. MATERIALS AND METHODS: Nine cast frameworks
      were fabricated on the mandibular master casts of 9 patients with 5 implants each
      following the well-established conventional fabrication technique. The frameworks
      were then laser scanned, and 9 CNC-milled titanium frameworks matching the
      outline of the conventional frameworks were fabricated. The accuracy of fit of
      both framework types was measured using a contact-type coordinate measuring
      machine and a computer program developed specifically for this purpose.
      Statistical analysis was done by a series of paired ttests. RESULTS: The laser
      scanned CNC-milled frameworks showed significantly less distortion along the x
      axis (transversal, d(x)) compared with the conventional frameworks (means: 33.7
      microm and 49.2 microm, respectively) (P = .011). The titanium frameworks also
      demonstrated significantly less distortion on the horizontal plane compared with
      the conventional frameworks (means: 56 microm and 85 microm, respectively) (P =
      .012). The d(y) (sagittal) and d(z) (vertical) axes and total 3D distortion
      (square root of dx(2) + dy(2) + dz(2)) showed less distortion overall in the
      laser-scanned CNC-milled frameworks, but this was not statistically significant
      (mean: 22.3 vs 35.6 microm, 13.3 vs 59.2 microm, 51 vs 114.1 microm,
      respectively, for y, z, and 3D distortion). CONCLUSION: Within the limitations of
      this study, fabrication of an implant-prosthodontic framework using the CNC
      milling technique yields a more accurate fit than the currently used cast
      technique. In vivo studies are needed to investigate the clinical significance of
      this recorded difference.

PMID- 17455432
TI  - Oral prostheses and oral health-related quality of life: a survey study of an
      adult Swedish population.
AB  - PURPOSE: The purpose of the study was to investigate whether oral health-related
      quality of life (OHRQOL) in an adult Swedish population could be explained by
      social attributes; individual attributes; dental status, with a special focus on
      the role of prosthodontics; and dental care attitudes. MATERIALS AND METHODS: The
      study was based on responses to a questionnaire sent in 1998 to a random sample
      of 1,974 persons aged 50 to 75 years (66% response rate). Three factors
      representing various aspects of OHRQOL were set as dependent variables in
      multiple-regression models: oral health impact on everyday activities, oral
      health impact on the psychologic dimension, and oral health impact on oral
      function. Independent variables in the models were social attributes, individual
      attributes, number of teeth, denture (ie, type of denture, if present), and
      dental care attitudes. RESULTS: General health in relation to age peers had the
      strongest association with all 3 dependent variables, followed by number of teeth
      and need care--cost barrier. When number of teeth was excluded, removable denture
      was found to covary with the dependent variables in each of the 3 regression
      models. CONCLUSION: The number of remaining teeth is more important than the type
      of denture in explaining OHRQOL. It is less important that a denture is fixed for
      those with few remaining teeth, in contrast to all others. Explanations are also
      found in general health and various aspects of dental care costs.

PMID- 17455433
TI  - Cervicofacial and mediastinal emphysema after crown preparation: a rare
      complication.
AB  - Cervicofacial emphysema is a well-known complication associated with the use of a
      high-speed air turbine. However, retropharyngeal emphysema or pneumomediastinum
      in the absence of severe trauma is rare. Immediate recognition of this phenomenon
      is essential to avoid life-threatening complications such as potential airway
      obstruction or venous air embolism. This article reports a case of gas diffusion
      into the mediastinum after dental preparatory treatment for a single-tooth crown.
      Pneumomediastinum should be considered whenever there are anamnestic data for
      retrosternal chest pain accompanied by dysphagia, dysphonia, or dyspnea caused by
      cervicofacial emphysema after dental treatment.

PMID- 17455434
TI  - Masticatory performance in postmaxillectomy patients with edentulous maxillae
      fitted with obturator prostheses.
AB  - PURPOSE: Oral cancer develops frequently in older populations. In Japan, the
      incidence of oral and pharyngeal cancer is 9,201 per year, with such tumors
      accounting for 1.74% of all cancers. Although obturator prostheses play an
      important role in the rehabilitation of postmaxillectomy patients, clinicians
      sometimes experience difficulty in placing obturator prostheses in edentulous
      maxillae, and criteria for the objective evaluation of treatment outcome have yet
      to be established. The present study aimed to investigate postsurgical factors
      influencing the masticatory performance of postmaxillectomy patients with
      edentulous maxillae fitted with obturator prostheses. MATERIALS AND METHODS: The
      extent of the hard palate defect, status of the mandibular dentition, mouth
      opening distance, and maximum occlusal force were investigated, and masticatory
      performance was measured using a testing gummy jelly in 27 postmaxillectomy
      patients with edentulous maxillae fitted with obturator prostheses. The influence
      of these items was evaluated quantitatively, and theoretical masticatory
      performance for each subject was calculated using multiple-regression analysis
      (quantification method type 1). RESULTS: Although average masticatory performance
      was almost equivalent to that of healthy, independent older patients with
      occlusal support classified as Eichner C, considerable individual variation was
      noted among subjects. The order of strength of influence on masticatory
      performance was identified by category weight: extent of hard palate defect >
      status of posterior mandibular teeth > maximum occlusal force > mouth-opening
      distance. A relatively high correlation (R2 = 0.78, P < .01, Pearson correlation
      coefficient) was evident between theoretical and actual values. CONCLUSION:
      Masticatory performance could be predicted by evaluating postsurgical factors in
      patients with edentulous maxillae fitted with obturator prostheses.

PMID- 17455435
TI  - Survival of complete crowns and periodontal health: 18-year retrospective study.
AB  - PURPOSE: This study investigated the survival of complete crowns in relation to
      periodontal variables on a long-term basis. MATERIALS AND METHODS: A total of
      1,037 complete crowns made in an undergraduate clinic for 456 patients were
      evaluated over an 18-year period. The study population was a mixture of
      periodontally affected and non-periodontally affected patients, which is
      comparable to the population group in a private practice. Patients were offered a
      supportive maintenance program. Periodontal variables were measured, including
      Plaque Index (PI), bleeding on probing (BOP), probing pocket depth (PPD), and
      attachment level. The Community Periodontal Index for Treatment Needs (CPITN) was
      calculated per sextant in a full-mouth assessment. RESULTS: The estimated
      survival rate was 78% at year 18. For the surviving restorations, the improved PI
      over time was statistically significant (P = .001). Odds ratios were 1.00 for
      both PI and BOP. For the CPITN, odds ratios were 3.00 to 3.83. Caries was the
      most frequent reason for failure, followed by periodontal disease. CONCLUSION: PI
      and BOP were not directly related to the frequency of failures. Patients with a
      high CPITN at baseline had a 3.8 times greater likelihood of losing a complete
      crown (and abutment tooth) than patients with a low CPITN. The higher failure
      rate was related not only to periodontal disease, but also to a wide range of
      biologic and technical problems. In relation to complete crown survival, caution
      is needed in patients with a high CPITN at baseline. Prosthetic work should be
      preceded by periodontal examination and prophylactic and periodontal treatment if
      needed.

PMID- 17455436
TI  - A new coping for overdentures. Part 1: A pilot study of the marginal precision.
AB  - The aim of this study was to investigate the marginal precision of new chairside
      copings prepared on 20 extracted teeth. The marginal fit was examined
      microscopically through 360-degree external observations. Subsequently, 10 new
      copings were adapted in vivo on 10 teeth that were planned for extraction. After
      extraction, the marginal fit was evaluated using the same protocol. The mean
      values of the marginal gap for the 2 groups (20 and 10 copings) were 24.1 and
      32.6 microm, respectively. The marginal precision of the new copings was within
      the clinically accepted limits.

PMID- 17455437
TI  - Discrepancy between satisfaction with mastication, food acceptability, and
      masticatory performance in older adults.
AB  - PURPOSE: The purpose of this study was to investigate the relationship between
      self-assessed satisfaction with mastication and food acceptability and
      masticatory performance in a large sample of older adults with various occlusal
      statuses. MATERIALS AND METHODS: The subjects were 708 community-dwelling,
      independently living elderly persons (351 men and 357 women) with a mean age of
      66.0 (SD: 4.2) years. Satisfaction with masticatory function and food
      acceptability (apples, grilled beef, and hard rice crackers) were evaluated using
      questionnaires. Masticatory performance was determined using test gummy jellies
      developed for measuring masticatory performance. Subjects were grouped into 3
      categories by posterior occlusal contacts according to the Eichner Index. The
      Kruskal-Wallis test and a multiple logistic regression analysis for
      dissatisfaction with masticatory function were conducted. RESULTS: Overall,
      posterior occlusal contacts, food acceptability, and masticatory performance were
      associated with satisfaction with masticatory function when evaluated with
      bivariate analysis. Multiple logistic regression analysis showed that the number
      of foods that could be eaten without difficulty was the most important
      explanatory variable for dissatisfaction with masticatory function (P < .01). In
      contrast, objective masticatory performance was not significantly associated with
      dissatisfaction with masticatory function (P = .057) after controlling for
      posterior occlusal contacts and food acceptance. CONCLUSIONS: The subjective
      masticatory function was associated not only with objective masticatory
      performance, but also with an individual's posterior occlusal contacts.

PMID- 17455438
TI  - A short-term clinical evaluation of IPS Empress 2 crowns.
AB  - PURPOSE: The aim of this study was to evaluate the clinical performance of all
      ceramic crowns made with the IPS Empress 2 system after an observation period of
      12 to 60 months. MATERIALS AND METHODS: Seventy-nine IPS Empress 2 crowns were
      placed in 21 patients. The all-ceramic crowns were evaluated clinically,
      radiographically, and using clinical photographs. The evaluations took place at
      baseline (2 days after cementation) and at 6-month intervals for 12 to 60 months.
      Survival rate of the crowns was determined using Kaplan-Meier statistical
      analysis. RESULTS: Based on the US Public Health Service criteria, 95.24% of the
      crowns were rated satisfactory after a mean follow-up period of 58 months.
      Fracture was registered in only 1 crown. One endodontically treated tooth failed
      as a result of fracture at the cervical margin area. CONCLUSION: In this in vivo
      study, IPS Empress 2 crowns exhibited a satisfactory clinical performance during
      an observation period ranging from 12 to 60 months.

PMID- 17455439
TI  - Influence of clinical baseline findings on the survival of 2 post systems: a
      randomized clinical trial.
AB  - PURPOSE: The aim of this prospective randomized controlled trial was to evaluate
      the influence of clinical baseline characteristics on the survival of 2 post
      systems. MATERIALS AND METHODS: One hundred patients needing a post were
      included. Half the patients received a glass fiber-reinforced post (FRP), and the
      other half received metal screw posts (MSP). The posts were assigned randomly. In
      addition to demographic data, the following parameters were recorded: type of
      tooth (incisor/canine versus molar/premolar), length of the post in relation to
      root length (percentage), extent of coronal tooth destruction (percentage),
      ferrule height (in millimeters), type of restoration (fixed or removable partial
      denture), and presence of antagonistic contacts (yes/no). After at least 1 year
      (mean: 13.84 months), the patients were recalled. Statistical analysis was
      performed using the log-rank test and Cox regression analysis. RESULTS: The
      survival rate of FRPs was 93.5%. In the MSP group, the survival rate was
      significantly lower (75.6%; log-rank test, P = .049). Additionally, the metal
      posts were associated with more unfavorable complications, for example, root
      fracture. The type of the tooth and the degree of coronal tooth destruction
      influenced the survival of MSPs, whereas no influence of these variables could be
      seen for FRPs. CONCLUSION: FRPs are superior to MSPs with respect to short-term
      clinical performance. Especially for MSPs, clinical survival depends on several
      variables.

PMID- 17455440
TI  - A new coping for overdentures. Part 2: Preliminary results of a clinical study.
AB  - The aim of this study was to evaluate a new type of coping used for overdentures.
      Twenty-nine patients received 60 new chairside copings prepared by 3 operators.
      The copings, used to anchor removable prostheses, were followed up for between 6
      months and 4 years with inspection, probing, and radiographic evaluation. Five
      teeth (8.3%) were extracted. A few clinical problems occurred, including
      decementation, periodontal pathology (loss of support and bleeding on probing),
      subgingival decay, and root fracture. No differences were noted in the incidence
      of complications among the 3 operators. The study demonstrated the clinical
      predictability of the new copings.

PMID- 17455441
TI  - Comparison of acid clearance of noncarbonated and carbonated soft drinks in the
      mouth.
AB  - The aim of this study was to measure differences in oral pH after subjects drank
      carbonated and noncarbonated acidic soft drinks. Oral pH was measured in 17
      subjects at 4 oral sites with beetrode electrodes after each subject drank 50 mL
      of noncarbonated and carbonated blackcurrant beverages. There were no statistical
      differences for either beverage regarding the time taken to recover a pH of 5.5,
      6.0, and 6.5. Oral pH recovered to 6.5 within 90 seconds with both drinks. The
      median lowest pH recorded after 30 seconds at the 4 sites for both drinks was >
      pH 4.9, but there was no statistical difference in the clearance between the
      drinks. The implication may be that carbonation is not directly responsible for
      the erosive potential of different beverages.

PMID- 17455442
TI  - Prosthodontics and the patient. Part 2: Need becoming demand, demand becoming
      utilization.
AB  - PURPOSE: Patients' oral health needs are estimated through dialogue and
      professional assessment. The concepts of need and demand are vital to studies of
      dental care and oral health. Need does not always lead to demand for treatment or
      to utilization, depending on the gatekeeping processes between need and demand
      and between demand and utilization. Demand must be accepted with the
      understanding that there is no objective need and that demand depends on the
      patient's opinion. In accordance with this, the need for prosthodontic treatment
      is highly individual and is not automatically related to oral health status,
      making need and demand difficult to measure in that respect. Therefore,
      sociodental factors should be included and evaluated in studies of need and
      demand for utilization of prosthodontic care. MATERIALS AND METHODS: This
      theoretical and analytic paper focuses on the gatekeeping processes between need
      and demand and between demand and utilization of prosthodontic care. RESULTS: The
      concept of gatekeeping refers to the social and psychologic processes that
      transform need into demand and demand into utilization. It implies that they are
      complex processes that can render great differences between demand and actual
      utilization. CONCLUSION: It is not possible to estimate a patient's needs for
      prosthodontic care, since there is no objective need. Demand and utilization are
      factors that play an important role in the gatekeeping process. These factors are
      dependent on the patient's opinion, which is influenced by numerous factors.

PMID- 17455443
TI  - A laboratory comparison of individual Targis/Vectris posts with standard
      fiberglass posts.
AB  - This article presents an in vitro analysis of a specific occlusal loading test on
      endodontically treated teeth restored with 2 different composite post materials.
      Individual, customized posts (IFPs) were compared to standard fiberglass posts
      (SFPs). The selected IFPs (standard cylindric Targis/Vectris posts) were compared
      to SFPs (Conic 6% Post, Ghimas). The posts were first subjected to a 3-point
      bending test to compare their flexural elastic properties. They were then used to
      restore 22 endodontically treated artificial maxillary central incisors and
      subjected to a specific occlusal loading simulation test. The loading test showed
      that IFP restorations performed better than SFP restorations. A clinical
      evaluation of this laboratory observation is suggested.

PMID- 17455444
TI  - Finite element analysis of stress-breaking attachments on maxillary implant
      retained overdentures.
AB  - PURPOSE: The purpose of this study was to examine the effect of stress-breaking
      attachments at the connections between maxillary palateless overdentures and
      implants. MATERIALS AND METHODS: Three-dimensional finite element models were
      used to reproduce an edentulous human maxilla with an implant-retained
      overdenture. Two-implant models (in the canine tooth positions on both sides) and
      four-implant models (in the canine and second premolar tooth positions on both
      sides) were examined. Stress-breaking material connecting the implants and
      denture was included around each abutment. Axial loads of 100 N were applied to
      the occlusal surface at the left first molar tooth positions. In each model, the
      influence of the stress-breaking attachments was compared by changing the elastic
      modulus from 1 to 3,000 MPa and the thickness of the stress-breaking material
      from 1 to 3 mm. Maximum stress at the implant-bone interface and stress at the
      cortical bone surface just under the loading point were calculated. RESULTS: In
      all models, maximum stress at the implant-bone interface with implants located in
      the canine tooth position was generated at the peri-implant bone on the loading
      side. As the elastic modulus of the stress-breaking materials increased, the
      stress increased at the implant-bone interface and decreased at the cortical bone
      surface. Moreover, stress at the implant-bone interface with 3-mm-thick stress
      breaking material was smaller than that with 1-mm-thick material. CONCLUSION:
      Within the limitations of this experiment, stress generated at the implant-bone
      interface could be controlled by altering the elastic modulus and thickness of
      the stress-breaking materials.

PMID- 17455445
TI  - Bond strength of acrylic teeth to denture base resin after various surface
      conditioning methods before and after thermocycling.
AB  - This study aimed to evaluate the durability of adhesion between acrylic teeth and
      denture base acrylic resin. The base surfaces of 24 acrylic teeth were flatted
      and submitted to 4 surface treatment methods: SM1 (control): No SM; SM2:
      application of a methyl methacrylate-based bonding agent (Vitacol); SM3: air
      abrasion with 30-microm silicone oxide plus silane; SM4: SM3 plus SM2. A heat
      polymerized acrylic resin was applied to the teeth. Thereafter, bar specimens
      were produced for the microtensile test at dry and thermocyled conditions (60
      days water storage followed by 12,000 cycles). The results showed that bond
      strength was significantly affected by the SM (P < .0001) (SM4 = SM2 > SM3 > SM1)
      and storage regimens (P < .0001) (dry > thermocycled). The methyl methacrylate
      based adhesive showed the highest bond strength.

PMID- 17455446
TI  - Multi drug resistant tuberculosis.

PMID- 17455447
TI  - Seasonal variation and prevalence of tuberculosis among health seekers in the
      South Western Cameroon.
AB  - OBJECTIVES: To determine the prevalence of tuberculosis (TB) in Fako health
      District, to assess the effects of seasonal variation on the incidence of TB in
      the study area and to use sentinel analysis to predict areas of greatest
      infection. DESIGN: A prospective cross sectional study based on laboratory
      investigations. SETTING: Fako health District, South Western Cameroon. RESULTS:
      The prevalence of TB was 23.3%. Tuberculosis was significantly more prevalent in
      males (12.6%) as compared with females (10.7%) (P = 0.034). TB prevalence was
      significantly different between age groups, with the highest number of cases
      recorded in the age group 21-30 (P = 0.002). When the health areas were compared,
      TB prevalence varied significantly (P = 0.001), with Limbe Town recording the
      highest number of TB cases. We recorded more TB cases in the wet season compared
      with the dry season and the difference was statistically significant (P = 0.000).
      There was a significant drop in the prevalence of TB over the study period (P =
      0.000). CONCLUSION: This study is the first to report on the effects of season on
      the prevalence of TB in Cameroon. These findings will therefore provide
      additional useful base line data for setting up TB control strategies in
      Cameroon.

PMID- 17455448
TI  - Routine use of antimicrobial drugs during the 2004 cholera epidemic in Douala,
      Cameroon.
AB  - OBJECTIVES: To evaluate routine use of antimicrobial drugs for treatment and
      prevention of cholera with special regards to the evolution of the antimicrobial
      drug resistance patterns of V. cholerae strains. DESIGN: Retrospective population
      based descriptive study. SUBJECTS: Four thousand nine hundred and forty one
      notified cholera cases, their 15,381 patients' guards and their 159,263 household
      members and close neighbours. RESULTS: A total of 4,941 patients received
      antibiotic therapy according to the treatment protocols. Prophylactic treatment
      was administered to 15,381 patients' guards in hospitals and to 159,263 household
      members and close neighbours during home visits. Over the entire outbreak, the
      antimicrobial susceptibility patterns of V. cholerae strains isolated remained
      stable. CONCLUSIONS: The routine use of antimicrobial therapy for cholera cases
      associated with simultaneous and large scale chemoprophylaxis of close contacts
      does not seem in our experience to compromise the stability of V. cholerae
      susceptibility profiles to drugs when applied within a comprehensive package of
      rigorously monitored community interventions. The role of therapy and
      chemoprophylaxis in limiting the extent of a cholera epidemic is however
      difficult to ascertain from our experience. Field trials need to be designed to
      elucidate this aspect.

PMID- 17455449
TI  - Influence of urbanisation on asymptomatic malaria in school children in Molyko,
      South West Cameroon.
AB  - OBJECTIVE: To determine the impact of urbanisation on the prevalence of
      asymptomatic malaria in Molyko, a rapidly urbanising area of South West Cameroon.
      DESIGN: A cross-sectional study. SETTING: Molyko, South West Province Cameroon.
      SUBJECTS: One hundred and sixty six and two hundred and forty four randomly
      selected children in Molyko in the rainy seasons of 2000 and 2004 respectively.
      MAIN OUTCOME MEASURES: Prevalence and geometric mean parasite density of
      asymptomatic malaria, measurement of axillary temperatures and haematocrit (PCV)
      values in 2000 and 2004. RESULTS: There was a significant association between
      axillary temperature and malaria parasitaemia in both years (p<0.05). Overall,
      the prevalence of asymptomatic malaria and parasite density values in all age
      groups in 2004 were lower than in 2000 while the reverse was the case with PCV
      values. CONCLUSION: Urbanisation in Molyko has likely reduced the level of
      malaria endemicity in the area. It is advisable to repeat this study over a
      period of time in order to assess the long-term effects of urbanisation in the
      study area.

PMID- 17455450
TI  - Maternal knowledge on mother-to-child transmission of HIV and breastmilk
      alternatives for HIV positive mothers in Homa Bay District Hospital, Kenya.
AB  - BACKGROUND: Mother- to- Child Transmission (MTCT) of HIV is a relatively new
      concept in rural populations and despite the huge amount of work that has been
      done on the HIV/AIDS, there still remains a dearth of information in knowledge of
      mothers on this concept especially in areas related to appropriate feeding
      methods for infants born to mothers infected with the virus. OBJECTIVES: To
      determine maternal knowledge on MTCT of HIV in the rural setting and to examine
      viable breastmilk alternatives for mothers who would be HIV positive. DESIGN: A
      cross- sectional study, supported by an observational study. SETTING: A rural
      district community and Homa-Bay District Hospital in South Western Kenya.
      SUBJECTS: One hundred and twelve non-tested mothers having infants aged 0-12
      months in the community and a sub-group (10%) of HIV positive mothers from the
      District Hospital. RESULTS: Maternal knowledge on MTCT of HIV was as low as 8.9%
      in the study area. The MTCT knowledge was found to influence the alternative
      feeding choice as mentioned by the non-tested mothers (p = 0.001; OR = 1.41;
      95%CI, 1.04-3.86). Those with high MTCT knowledge tended to be more receptive and
      considered feeding alternatives other than cowmilk like expressed breastmilk (p =
      0.1 5), formula (p = 0.036; OR = 2.44; 95%CI, 1.66-6.04) and milk from milk bank
      (p = 0.015; OR = 1.34; 95%CI, 1.13-5.50) than their counterparts with low MTCT
      knowledge. Cowmilk, formula and wet-nursing were the three feeding alternatives
      that were viable with varying socio-cultural, economic and/or nutritional
      constraints. CONCLUSION: Maternal MTCT knowledge influences the choice of
      alternative infant feeding option but not breastfeeding practices. Cowmilk is the
      most common, socio-culturally acceptable and accessible breastmilk alternative in
      this community. It is recommended that in order to improve MTCT knowledge, health
      education and nutrition counselling be intensified in PMTCT programmes, VCT
      centers and ANC clinics. Concurrently, effort should be made to increase the
      supply of cowmilk within the community so as to make it more readily available
      and affordable.

PMID- 17455451
TI  - Nutritional status and food consumption patterns of young children living in
      Western Uganda.
AB  - OBJECTIVES: The aim of this pilot study was to compare the nutritional status and
      food consumption patterns of children under five years. DESIGN: Quantitative,
      exploratory, cross sectional study. SETTING: Kabarole district, western Uganda.
      Kabarole district is a rural district with subsistence farming as the main
      income. SUBJECTS: Two hundred and five children between 12 and 72 months of age
      living in AIDS affected homes versus children living in non-AIDS affected homes
      were examined. RESULTS: Fifty-five percent of all children were stunted and 20.5%
      were underweight. There was no difference in the prevalence of malnutrition
      between children living in AIDS affected homes versus non-AIDS affected homes.
      Only children between 12-35 months suffered from a daily deficit in caloric
      intake. The older children consumed the basic recommended daily intake (RDI) for
      protein, fat, iron and vitamin A. Due to frequent disease episodes and
      limitations in the estimations of individual total energy expenditure, the
      results are likely underestimations of the children's true nutritional
      requirements. The type of foods given to children in AIDS affected homes and
      controls were quite similar. CONCLUSION: Young children in Kabarole district
      suffer from severe chronic malnutrition rates, but rates and feeding patterns are
      not different in AIDS affected versus non AIDS affected homes.

PMID- 17455452
TI  - Medicolegal autopsies in North Central Nigeria.
AB  - OBJECTIVE: To determine the pattern and the causes of deaths reported to the
      coroner for medicolegal autopsies in North Central Nigeria. DESIGN: A descriptive
      retrospective study. SETTING: Jos University Teaching Hospital, Jos, Nigeria
      between January 1996 to December 2003. SUBJECTS: Autopsies reports of 279
      subjects whose causes of death were subjects of litigation. MAIN OUTCOME
      MEASURES: The causes of death in medicolegal autopsies. RESULTS: A total of 279
      cases of medicolegal autopsies with identified causes of death were recorded
      representing 89% of all the autopsy examinations performed within the period. In
      7.6% of cases, there was no identifiable cause of death. There were 127 males
      against 52 females with a male: female ratio of 4.5:1 and their ages ranged
      between two and 74 years with a mean of 34.7+/-8.2 years. Children aged < 15
      years made up 29% of the cases and were distributed as follows: 4% of the
      children were aged 0-5 years, 9% between six to ten years while 17% were between
      11 - 15 years. Accidental deaths made up 51% of the cases, homicides 36% and
      sudden deaths 13%. Road traffic accidents were responsible for 76% of all
      accidental deaths. Children were affected in 34% of the accidental deaths and
      half of them were pedestrians at the time of accident. The male: female ratio of
      deaths from road traffic accidents was 3:1 with mean age of 24 years. In all the
      accidental deaths, abdominal injuries were responsible for 47% while 30% died
      from chest injuries. Of the homicide cases male subjects outnumbered female in a
      ratio of 16:1 and children were affected in 28% of homicides. Injuries sustained
      during ethnic and religious crisis were responsible for 48% of the deaths from
      homicide and 15% of them were children. Armed robbery was responsible for 28%
      cases while physical assaults were responsible for 20% of homicides. Chest
      injuries were the causes of death in 54% and abdominal injuries in 36% of
      homicides. Cardiovascular deaths were responsible for 63% cases of all sudden
      natural deaths referred for Coroner's inquest during the period. Children made up
      11% of all sudden natural deaths. Males outnumbered females in cardiovascular
      deaths in a ratio of 6:1 and 46% cases of them died of hypertensive heart
      failure, 32% had cerebrovascular accidents, pulmonary embolism in 13.6% and
      myocardial infarction in 9%. One case of myocardial infarction died during
      intercourse. CONCLUSION: Road traffic accidents, violent communal unrest and
      armed robbery were responsible for 66% of the medicolegal autopsies in our
      environment. Public enlightenment, good road maintenance and safe driving culture
      as well as sustainable security for life and property would reduce the incidence
      of preventable deaths.

PMID- 17455453
TI  - Corneal diameters in infants born in two hospitals in Ibadan, Nigeria.
AB  - OBJECTIVES: To measure the horizontal corneal diameters in infants at birth and
      compare with values reported in other studies. DESIGN: A cross-sectional hospital
      based study. SUBJECTS: All the healthy infants born within the period of one
      month in these hospitals were eligible for enrolment into the study. Horizontal
      corneal diameter measurements were performed with indirect caliper in both eyes
      of each of the 342 healthy full term infants and 25 preterm healthy infants born
      in these two hospitals. These results were evaluated according to the age of the
      infants RESULTS: The corneal diameter in term infants was found to range from
      9.00 mm to 12.50 mm during the first week of life with a mean of 10.26 mm (SD +/
      0.59 mm, n = 64). This is higher than what was reported for Caucasian infants (P
      < 0.01). Mean horizontal corneal diameter in all male infants aged 1-238 days was
      11.06 mm (SD 0.75 mm, n = 187), slightly higher than 10.93 mm (SD 0.22 mm, n =
      154) in all females, though this difference was not statistically significant.
      Horizontal corneal diameter increased progressively with age, from a mean value
      (SD) of 10.26 mm (0.72) to a mean value (SD) of 12.0 mm at 34 weeks of age. There
      was no significant difference in the mean corneal diameter of the right and left
      cornea. A few infants had corneal diameters of 12.50 mm and had no congenital
      glaucoma. Mean corneal diameter in preterm infants less than 37 weeks of
      gestation was 8.90 mm at birth (SD 1.25 mm, n = 25). CONCLUSION: The horizontal
      diameter increased with age from birth to the 34 weeks of age. Changes after this
      period were not studied. The values obtained in these African infants were
      slightly higher than those reported from other populations.

PMID- 17455454
TI  - Extreme hyperkalaemia secondary to malignant ureteric obstruction: case report.
AB  - We report a case of a 42 year old patient who collapsed at an airport departure
      lounge. The patient was investigated and found to have advanced renal failure
      with serum potassium (K+) of 10.3 mmol/L, creatinine of 3581 pmol/L and urea of
      59.9 mmol/L secondary to obstructive uropathy due to advanced bladder cancer.
      Although these biochemical changes were thought to be incompatible with life, he
      made a slow recovery following haemodialysis and insertion of bilateral
      percutaneous nephrostomy tubes.

PMID- 17455455
TI  - [Secondary metabolites accumulating and geoherbs formation under enviromental
      stress].
AB  - This paper analyzed how habitat affected the formation of geoherbs after
      summarizing the influences of environmental stress on plants growth, especially
      on theirs secondary metabolites accumulating, and introducing 4 kinds hypothesis
      about environmental stress affects plants. It was then pointed out that
      environmental stress may have advantage on the formation of geoherbs. The stress
      effect hypothesis on forming geoherbs was brought forward, and the ways and
      methods on study the geoherbs under environmental stress was discussed.

PMID- 17455456
TI  - [Progress in studies on anti-hepatoma effect of traditional Chinese medicine by
      adjusting immune function].
AB  - We surveyed the literatures domestic and abroad, and summarized traditional
      Chinese medicine (single or complex prescription) with anti-hepatoma effects by
      adjusting immune function. Traditional Chinese medicine showed great advantages
      in improving the immune system function of the organism in various ways, so they
      could prohibit the generation and development of tumor, lessen the damage caused
      by chemotherapeutics, increase the sensitivity of chemotherapeutics, strengthen
      immune surveillance to tumor cells, elevate living quatity of patients and
      prolong their living time. It is very promising to exploit much more effective
      anti-tumor drugs from TCM.

PMID- 17455457
TI  - [Analysis of detecting methods of digoxin blood drug level].
AB  - Digoxin plays a part in healing of congestive heart failure in clinic. Its
      therapeutic dose is very approximate to toxic dose and even they overlap each
      other sometimes. There are many influencing factors on blood drug level of
      digoxin. Pharmacodynamics and pharmacokinetics varies with different
      individuality. It is indispensable to detecting blood drug level in order to
      treat disease and prevent intoxication. Integrating with the detecting-methods of
      blood drug level of digoxin home and broad, characteristic of many methods are
      summarized from sensitivity, linearity range, cross-reaction and precision. These
      methods include radio immunoassay, enzyme immunoassay, chemiluminescence
      immunoassay, fluorescence immunoassay and HPLC-MS-MS. These methods are popular
      for their specialized ascendancy. The cost of radio immunoassay is low. Enzyme
      immunoassay has good specificity. Sensitivity and stability of chemiluminescence
      immunoassay is very excellent. Fluorescence polarization immunoassay is sensitive
      and convenient. HPLC-MS-MS has high resolution and good specificity. One of the
      development tendencies is to combine two or more methods in detecting the blood
      drug level of digoxin which contribute to these methods integrated use.

PMID- 17455458
TI  - [Microarray and research of Chinese medications: pharmcogenomics of Chinese
      medications].
AB  - The mechanism of Chinese medications have some characteristic such as multi
      pathway, multi-components, multi-targets and so on, which decide the direction of
      systems research. In the recent years, microarrays be concerned with the relative
      field of Chinese medications for its superiority of highthough, parallel and high
      density. This paper mainly generalize the approach of these methods in the recent
      three years, such as finding effective target of Chinese medications, effective
      part of Chinese medications, checkup of Chinese medications, screening new drugs
      and so on. We suggest the concept of Pharmacogenomics of Chinese medications with
      the guidance of the theory of Chinese medications for further development of
      Chinese medications.

PMID- 17455459
TI  - [Effect of seedling and fertilizering on yield and quality of cultivated Changium
      smyrnioides].
AB  - OBJECTIVE: To study the effects of seedling and fertilizer on yield and quality
      of cultivated Changium smyrnioides and build a basis for its GAP. METHOD:
      Experiments were conducted to study the effects of seedling quality and different
      fertilizering measures on yield and quality of cultivated C. smyrnioides. RESULT:
      The seedling and fertilizering depth affected the yield of roots obviously.
      Organic fertilizer combined with nitrogen and phosphorus could increase the
      amylose content obviously. CONCLUSION: In cultivation, the seedling (root length
      > 5.0 cm, root diameter > 0.3 cm, fresh root weight > 0.3 g) is optimal. The
      ideal combination is nitrogen, phosphorus and organic fertilizer. The suggested
      fertilizering depth ranged from 10 to 15 cm.

PMID- 17455460
TI  - [Identification of Chinese medicine material of Fritillaria by
      themogravimetric/diffrential thermal analysis].
AB  - OBJECTIVE: To provide a quick and simple method to identify different Chinese
      medicine material of Fritillaria. METHOD: The thermograms and differential
      thermograms of nine Fritillaria powders were obtained by thermal analyzer.
      RESULT: By analyzing the thermograms of nine Fritillaria powders, we concluded
      that the thermal stability of nine Fritillaria powders was much different each
      other due to the different geography origin. The thermal stability of F.
      hupehensis was highest among nine Fritillaria, while F. ussurensis was the
      lowest. The different Fritillaria showed their own DTA spectra respectively.
      CONCLUSION: According to the differences in the thermal properties of nine
      Fritillaria powders, the origins of Fritillaria could be easily identfied.

PMID- 17455461
TI  - [Effects of methyl jasmonat on accumulation and release of tanshinones in
      suspension cultures of Salvia miltiorrhiza hairy root].
AB  - OBJECTIVE: To study the effects of methyl jasmonate (MJ) on the accumulation and
      release of tanshinones in suspension cultures of Salvia miltiorrhiza hairy roots.
      METHOD: After 18 day's suspension culture of S. miltiorrhiza hairy roots induced
      by Agrobacterium rhizogenes ATCC15834, the chemical elicitor--methyl jasmonat was
      added into 6-7V suspension cultures and at the same time, tanshinones contents
      (including cryptotanshinone and tanshinone II(A)) on the day 2, 6 and 9, after
      dealing with MJ, was quantified by HPLC. RESULT: After dealing with MJ on the day
      2, 6 and 9, the concentration of cryptotanshinone reached to 0.039, 0.204, 0.571
      mg x g(-1) respectively,and tanshinone II(A) reached 0.251, 0.601 and 1.563 mg x
      g(-1) respectively. After 9 day's treatment by MJ, the maximum increase of
      cryptotanshinone and tanshinone II(A) were 23.8 fold and 6.2 fold higher than
      that of the control respectively. CONCLUSION: MJ could stimulate the accumulation
      of tanshinones in S. miltiorrhiza and have released them into the culture medium.

PMID- 17455462
TI  - [Comparison of preparing two polylactide nanoparticles loaded lipophilic anti
      cancer herb drug by nanoprecipitation method].
AB  - This paper introduced an experimental study of polylacticacid (PLA) nanoparticles
      of lipophilic anti-cancer herb drug using a precipitation method. Cucurbitacins
      (Cu) and Curcuminoids (Cur) were selected to be model drugs. They had similar
      solubility but their incorporation effects were significantly different: the
      average drug entrapment ratio, the average drug loading and the average drug
      recovery were 38.53%, 2.21% and 27.02% respectively; while those of Cur-PLA-NP
      were 94.36%, 14.35% and 91.23% respectively. To analyse the reason, drug
      incorporation process was investigated. By measuring solvent evaporation rate,
      ratio of drug PLA precipitates, drug distribution in system and entrapping ratio
      at different time of preparation, we found the difference of precipitation
      velocity of drug was the main reason. We also concluded that not all lipophilic
      drug can be well entrapped into PLA nanoparticle by nanoprecipitation method. The
      drug incorporation depended on the interations among drug, PLA and organic
      solvents, in addition to the solubility of the drug.

PMID- 17455463
TI  - [Study on extraction technics and variety trends of the flavonoids in Sarcandrae
      glabra].
AB  - OBJECTIVE: To study on extraction technics and variety trends of the flavonoids
      in Sarcandrae glabra. METHOD: By using S. glabra in Guizhou as materials and the
      experiment of L9 (3(4)) by ethanol as extracting way, The variety trends of the
      flavonoids from S. glabra are studied under the optimum extracting conditions
      during different raw stored times, different gathering season, different S.
      glabra position. RESULT: The flavonoid's contains was more low when the raw
      material was stored more long and descended average 24.74% annually. The
      flavonoid's contains had the tallest in 10-12 month by gathering indifferent
      season. The flavonoids contains were the tallest in the leaf of S. glabra in
      Guizhou than in the root and stem, and the contains were the lowest in stem.
      CONCLUSION: The optimum conditions of extracting flavonoids from S. glabra are
      obtained when the condition is 60% of density of ethanol at 10 times of volume,
      80 degrees C of extracting temperature, 3 h of extracting hours, 3 times of
      extracting number of times in 10-12 month, in the leaf, the raw material was
      stored more shortest, the flavonoid's contains had the tallest.

PMID- 17455464
TI  - [Study on correlation between relative density and kinematical viscosity of
      concentration for Yuxianling granules].
AB  - OBJECTIVE: To study the relation between relative density and kinematical
      viscosity of the concentration for Yuxianling granules. METHOD: The relative
      density and kinematical viscosity by alkali burette of the concentration were
      investigated. The connection between kinematical viscosity and spray drying, also
      and temperature of the concentration was respected. In the meantime, different
      mathematical models were simulated. RESULT: Kinematical viscosity is susceptible
      than relative density to the effect for spray drying, and the mathematical model
      is also set up accordingly. The result can offer the proper inlet temperature and
      kinematical viscosity for spray drying. CONCLUSIon The method in the experiment
      is simple, practical and manipulate easily. The study will provide the basis for
      extracted solution of compression and spray drying.

PMID- 17455465
TI  - [Rapid determination of chlorogenic acid in aqueous solution of Flos Lonicerae
      Japonicae extraction].
AB  - OBJECTIVE: To establish a rapid method for the determination of chlorogenic acid
      in aqueous solution of Flos Lonicerae Japonicae extraction. METHOD: Chlorogenic
      acid content in aqueous solution of Flos Lonicerae Japonicae extraction was
      measured by RP-HPLC. The UV spectrum of the same samples were scanned
      simultaneously. The wavelength of the best correlation between UV absorbance and
      chlorogenic acid content determined by HPLC was chosen and the chlorogenic acid
      content of aqueous solution of Flos Lonicerae Japonicae extraction was estimated
      by prediction equation. Other 10 batches of aqueous solution of Flos Lonicerae
      Japonicae extraction was used for testing the equation by comparison of the
      values of chlorogenic acid content determined by HPLC and equation. RESULT: Good
      linearity of chlorogenic acid was obtained within the range of 0.09-2.25 microg
      by HPLC; The recovery was 100.4%; RSD was 1.1% (n = 5). The best wavelength in UV
      spectrum correlating with chlorogenic acid content was 294 nm. The prediction
      equation: chlorogenic acid content C = 2.703 425A(294 nm) - 0.129 18; Good
      correlation between chlorogenic acid content determined by HPLC and predicted
      results was found (r = 0.995 2, n = 11). RSD was 0.2% (n = 6). CONCLUSION: This
      method is simple, rapid and accurate for determination of chlorogenic acid and
      can be used for the rapid control of aqueous solution of Flos Lonicerae Japonicae
      extraction.

PMID- 17455466
TI  - [Saponins from roots of Hedysarum multijugum].
AB  - OBJECTIVE: To study the chemical constituents from the root of Hedysarum
      multijugum. METHOD: The compounds were separated by chromatographic methods,
      their structures were identified by spectral analysis. RESULT: Four compounds
      were isolated and identified as soyasaponin II methyl ester (1), soyasaponin II
      (2), soyasaponin Bg (3), and soyasaponin I (4). CONCLUSION: The four compounds
      were obtained from the plant for the first time. Compound 3 was isolated from the
      genus Hedysarum for the first time, and the NMR data of 3 was reported for the
      first time.

PMID- 17455467
TI  - [Studies on flavonoids of Oxytropis falcata].
AB  - OBJECTIVE: To investigate the flavonoids of Oxytropisfalcata. METHOD: Compounds
      were isolated by column chromatography using silica gel, Sephadex LH -20 and ODS
      as the adsorbents. Their structures were elucidated by NMR and MS spectroscopic
      data. RESULT: Eight compounds were isolated and elucidated as 2', 4'-dihydroxy-4
      methoxy chalcone (1), 2', 4'-dihydroxy chalcone (2), 5,7-dihydroxy-4'-methoxy
      flavonol (3), 7-hydroxy-4'-methoxy flavanones (4), 3', 7-dihydroxy-2',4'
      dimethoxy isoflavan (5), 2'-hydroxy-4'-methoxy chalcone (6), 2'-methoxy-4'
      hydroxy chalcone (7), 2',4'-dihydroxy dihydrochalcone (8). CONCLUSION: All
      compounds were obtained from O. falcata for the first time.

PMID- 17455468
TI  - [Chemical constituents of isoflavones from vine stems of Millettia nitita var.
      hirsutissima].
AB  - OBJECTIVE: To study the chemical constituents from the vine stems of isoflavones
      of Millettia nitita var. hirsutissima. METHOD: Chromatographic methods were used
      to isolate compounds, and spectroscopic methods were used to elucidate the
      structures. RESULT: Four isoflavones were isolated and identified: 3'-O
      methylorobol (1), genistein (2), biochanin A (3), afromosin (4). CONCLUSION: All
      Compounds were obtained from the plant for the first time.

PMID- 17455469
TI  - [Blood lipid-regulation of stilbene glycoside from polygonum multiflorum].
AB  - OBJECTIVE: To study lipid-regulating action of 2, 3, 5, 4'-tetrahydroxy stilbene
      2-O-beta-D-glucopyranoside (TSG) from Polygonum multiflorum on experimental model
      hyperlipidemic rats. METHOD: TSG 90 and 180 mg x kg(-10 x d(-1), atorvastatin mg
      kg(-1) x d(-1) and saline 2 mL x d(-1) were administered to hyperlipidemic rats.
      Groups of rats were determined and compared with those of saline group. The LDLR
      and HMGR mRNA expression were also detected. RESULT: TSG significantly reduced
      serum TC and LDL-C level and atherosclerosis index, increased the expression of
      LDLR in the liver cells. CONCLUSION: TSG, which shows effects and mechanism in
      part like atorcastatin, is a major constituent with blood-lipid regulating effect
      of P. multiflorum and can be explored as a potent medication for hyperlipidemia.
      Effects on LDL-C and AI, as well as on gene expression of TSG were first
      reported.

PMID- 17455470
TI  - [Effect of Shensu Yin on the expression of toll-like receptors and the downstream
      signaling components on RAW 264.7 cells].
AB  - OBJECTIVE: To investigate the influences of Shensu Yin to RAW 264.7 on the
      expression of TLR3, TLR4 and the factors of the downstream in RAW 264. 7 cells.
      METHOD: RAW 264.7 cell line was stimulated with Lipopolysaccharide and POLY I: C,
      respectively, and treated with the drug serum of Shensuyin simultaneously. 24
      hours later, collected the supernatant and measured the inflammatory factors TNF
      alpha and IFN-beta, extracted mRNA and measured the expression of TLR3, TLR4 and
      other correlated indexes of the downstream, analyzed and evaluated Shensu Yin's
      substance basis of pharmacodynamic actions. RESULT: Shensu Yin drug serum
      depressed the expression of TLR4, MyD88, TRAF-6, TRAM and TRIF mRNA, as a result,
      it decreased the amount of TNF-alpha and IFN-beta. CONCLUSION: Depressing the
      expression of TLR3, MyD88, TRAM and TRIF mRNA may be the elementary basis of
      Shensu Yin to play heat-clearing and detoxicating effect.

PMID- 17455471
TI  - [Effects and mechanism of lutein on apoptosis of esophageal carcinoma EC9706
      cells].
AB  - OBJECTIVE: To study the effects of lutein on apoptosis and its mechanism. METHOD:
      The cells of human esophageal carcinoma EC9706 were grown in RPMI medium
      containing 10% bovine serum and were treated with lutein at 100 microg x mL(-1)
      concentration. Flow cytometry was employed to investigate the effects of lutein
      on cell apoptosis of EC9706 cells. Histochemistry was performed to determine
      apoptosis-related protein expresion. RESULT: Flow cytometry analyses revealed
      that lutein increased EC9706 cell apoptosis ratio when treated with lutein 100
      microg x mL(-1) at 96 h. Lutein decreased the expression of Bcl-2 protein and
      increased the expression of Bax protein in EC9706 cells. CONCLUSION: Lutein could
      inhibit mitosis and stimulate apoptosis of EC9706 cells. The apoptotic effect may
      result from the down-regulation of expression of Bcl-2 and up-regulation
      expression of Bax.

PMID- 17455472
TI  - [Effect of Shenfu injection in postoperative recovery after abdominal surgery].
AB  - OBJECTIVE: To investigate the effect of Shenfu injection (SF) in postoperative
      recovery after abdominal surgery. METHOD: 150 patients were randomly divided into
      control group (75) and SF group (75). The efficacy were evaluated with the time
      of passage of gas by anus, information of wound healing, blood routine, blood
      coagulaton function, liver function. Changes recovery factor, immune index and
      hemorheological index were detected too. RESULT: The time of passage of gas by
      anus in SF group was significantly shorter than that in control group. Blood
      routine, blood coagulaton function, liver function showed no significant
      difference in the two group of preoperative and postoperative. Whole blood
      viscosity, blood reduced viscosity and plasma fibrinogen viscosity in SF group
      were significantly lower than that in control group after operation. IgG and IgA
      in SF group was significantly higher than that in control group after operation.
      IgG and CD4+/CD8+ in control group was significantly higher after operation than
      that in before operation. Among tissue damage plerosis correlation factor, the
      blood levels of superoxide dismutase (SOD) in SF group and control group is
      significantly lower than that in preoperation (P < 0.05), SOD in SF group was
      significantly higher than that in control group after operation. The blood levels
      of malondialdehyde (MDA) in SF group and control group is significantly higher
      than that in preoperation (P < 0.05). MDA in SF group was significantly lower
      than that in control group after operation. Whole blood viscosity, blood reduced
      viscosity and plasma fibrinogen viscosity in control group after operation were
      significantly higher than that before operation. CONCLUSION: SF can stimulate the
      immune system and reduce the blood viscosity. It is contribute to the patients'
      rehabilitation.

PMID- 17455473
TI  - Tunneling magnetoresistive heads for magnetic data storage.
AB  - Spintronics is emerging to be a new form of nanotechnologies, which utilizes not
      only the charge but also spin degree of freedom of electrons. Spin-dependent
      tunneling transport is one of the many kinds of physical phenomena involving
      spintronics, which has already found industrial applications. In this paper, we
      first provide a brief review on the basic physics and materials for magnetic
      tunnel junctions, followed more importantly by a detailed coverage on the
      application of magnetic tunneling devices in magnetic data storage. The use of
      tunneling magnetoresistive reading heads has helped to maintain a fast growth of
      areal density, which is one of the key advantages of hard disk drives as compared
      to solid-state memories. This review is focused on the first commercial tunneling
      magnetoresistive heads in the industry at an areal density of 80 approximately
      100 Gbit/in2 for both laptop and desktop Seagate hard disk drive products using
      longitudinal media. The first generation tunneling magnetoresistive products
      utilized a bottom stack of tunnel junctions and an abutted hard bias design. The
      output signal amplitude of these heads was 3 times larger than that of comparable
      giant magnetoresistive devices, resulting in a 0.6 decade bit error rate gain
      over the latter. This has enabled high component and drive yields. Due to the
      improved thermal dissipation of vertical geometry, the tunneling magnetoresistive
      head runs cooler with a better lifetime performance, and has demonstrated similar
      electrical-static-discharge robustness as the giant magnetoresistive devices. It
      has also demonstrated equivalent or better process and wafer yields compared to
      the latter. The tunneling magnetoresistive heads are proven to be a mature and
      capable reader technology. Using the same head design in conjunction with
      perpendicular recording media, an areal density of 274 Gbit/in2 has been
      demonstrated, and advanced tunneling magnetoresistive heads can reach 311
      Gbit/in2. Today, the tunneling magnetoresistive heads have become a mainstream
      technology for the hard disk industry and will still be a technology of choice
      for future hard disk products.

PMID- 17455474
TI  - Exchange coupling and its applications in magnetic data storage.
AB  - The continuing scaling of magnetic recording is facing more and more scientific
      and technological challenges because both the read sensor and recording bit are
      approaching sub-50 nm regime with the ever increasing areal density in hard disk
      drives. One of the key and indispensable elements for both high-sensitivity
      sensors and high-density media is the exchange bias between a ferromagnetic and
      an antiferromagnetic layer or the exchange coupling between two ferromagnets via
      a non-magnetic spacer. In the nanometer regime, the exchange coupling between
      ferromagnet and antiferromagnet or two ferromagnets through a conductive spacer
      is governed by the intergrain exchange interaction which has its origin in
      electron spins. Interlayer exchange coupling in multilayer or trilayer
      essentially originates from the quantum confinement effect. In this paper, we
      first review the physical origin and various theoretical models of the two types
      of exchange couplings, followed by a review of the applications of the exchange
      bias and interlayer exchange coupling in data storage with emphasis on the
      advanced read sensor and advanced media including perpendicular media and
      patterned media.

PMID- 17455476
TI  - Nanophase change for data storage applications.
AB  - Phase change materials are widely used for date storage. The most widespread and
      important applications are rewritable optical disc and Phase Change Random Access
      Memory (PCRAM), which utilizes the light and electric induced phase change
      respectively. For decades, miniaturization has been the major driving force to
      increase the density. Now the working unit area of the current data storage media
      is in the order of nano-scale. On the nano-scale, extreme dimensional and nano
      structural constraints and the large proportion of interfaces will cause the
      deviation of the phase change behavior from that of bulk. Hence an in-depth
      understanding of nanophase change and the related issues has become more and more
      important. Nanophase change can be defined as: phase change at the scale within
      nano range of 100 nm, which is size-dependent, interface-dominated and
      surrounding materials related. Nanophase change can be classified into two
      groups, thin film related and structure related. Film thickness and clapping
      materials are key factors for thin film type, while structure shape, size and
      surrounding materials are critical parameters for structure type. In this paper,
      the recent development of nanophase change is reviewed, including crystallization
      of small element at nano size, thickness dependence of crystallization, effect of
      clapping layer on the phase change of phase change thin film and so on. The
      applications of nanophase change technology on data storage is introduced,
      including optical recording such as super lattice like optical disc,
      initialization free disc, near field, super-RENS, dual layer, multi level, probe
      storage, and PCRAM including, superlattice-like structure, side edge structure,
      and line type structure. Future key research issues of nanophase change are also
      discussed.

PMID- 17455475
TI  - Advanced modeling techniques for micromagnetic systems.
AB  - We present a review of micromagnetic and magnetotransport modeling methods which
      go beyond the standard model. We first give a brief overview of the standard
      micromagnetic model, which for (i) the steady-state (equilibrium) solution is
      based on the minimization of the free energy functional, and for (ii) the
      dynamical solution, relies on the numerical solution of the Landau-Lifshitz
      Gilbert (LLG) equation. We present three complements to the standard model, i.e.,
      (i) magnetotransport calculations based on ohmic conduction in the presence of
      the anisotropic magnetoresistance (AMR) effect, (ii) magnetotransport
      calculations based on spin-dependent tunneling in the presence of single charge
      tunneling (Coulomb blockade) effect, and (iii) stochastic micromagnetics, which
      incorporates the effects of thermal fluctuations via a white-noise thermal field
      in the LLG equation. All three complements are of practical importance: (i)
      magnetotransport model either in the ohmic or tunneling transport regimes,
      enables the conversion of the micromagnetic results to the measurable quantity of
      magnetoresistance ratio, while (ii) stochastic modeling is essential as the
      dimensions of the micromagnetic system reduces to the deep submicron regime and
      approaches the superparamagnetic limit.

PMID- 17455478
TI  - Nanoscale ferroelectric information storage based on scanning nonlinear
      dielectric microscopy.
AB  - An investigation of ultrahigh-density ferroelectric data storage based on
      scanning nonlinear dielectric microscopy (SNDM) is described. For the purpose of
      obtaining fundamental knowledge on high-density ferroelectric data storage,
      several experiments on nanodomain formation in a lithium tantalate (LiTaO3)
      single crystal were conducted. Through domain engineering, a domain dot array
      with an areal density of 1.5 Tbit/inch2 was formed on congruent LiTaO3 (CLT). Sub
      nanosecond (500 psec) domain switching speed also has been achieved. Next, actual
      information storage is demonstrated at a density of 1 Tbit/inch2. Finally, it is
      described that application of a very small dc offset voltage is very effective in
      accelerating the domain switching speed and in stabilizing the reversed nano
      domain dots. Applying this offset application technique, we formed a smallest
      artificial nano-domain single dot of 5.1 nm in diameter and artificial nano
      domain dot-array with a memory density of 10.1 Tbit/inch2 and a bit spacing of
      8.0 nm, representing the highest memory density for rewritable data storage
      reported to date.

PMID- 17455477
TI  - Application of femtosecond-laser induced nanostructures in optical memory.
AB  - The femtosecond laser induced micro- and nanostructures for the application to
      the three-dimensional optical data storage are investigated. We have observed the
      increase of refractive index due to local densification and atomic defect
      generation, and demonstrated the real time observation of photothermal effect
      after the femtosecond laser irradiation inside a glass by the transient lens
      (TrL) method. The TrL signal showed a damped oscillation with about an 800 ps
      period. The essential feature of the oscillation can be reproduced by the
      pressure wave creation and propagation to the outward direction from the
      irradiated region. The simulation based on elastodynamics has shown that a large
      thermoelastic stress is relaxed by the generation of the pressure wave. In the
      case of soda-lime glass, the velocity of the pressure wave is almost same as the
      longitudinal sound velocity at room temperature (5.8 microm/ns). We have also
      observed the localized photo-reduction of Sm3+ to Sm2+ inside a transparent and
      colorless Sm(3+)-doped borate glass. Photoluminescence spectra showed that some
      the Sm3+ ions in the focal spot within the glass sample were reduced to Sm2+ ions
      after femtosecond laser irradiation. A photo-reduction bit of 200 nm in three
      dimensions can be recorded with a femtosecond laser and readout clearly by
      detecting the fluorescence excited by Ar+ laser (lambda = 488 nm). A photo
      reduction bit can be also erased by photo-oxidation with a cw Ar+ laser (lambda =
      514.5 nm). Since photo-reduction bits can be spaced 150 nm apart in a layer
      within glass, a memory capacity of as high as 1 Tbit can be achieved in a glass
      piece with dimensions of 10 mm x 10 mm x 1 mm. We have also demonstrated the
      first observation of the polarization-dependent periodic nanostructure formation
      by the interference between femtosecond laser light and electron acoustic waves.
      The observed nanostructures are the smallest embedded structures ever created by
      light. The period of self-organized nanostructures can be controlled from
      approximately 140 to 320 nm by the pulse energy and the number of irradiated
      pulses. Furthermore, we have also observed the self-assembled sub-wavelength
      periodic structures created in silica glass by femtosecond pulses on the plane of
      the propagation of light.

PMID- 17455479
TI  - Magnetic random access memory (MRAM).
AB  - The high density and high speed nonvolatile MTJ MRAMs are reviewed from
      perspective of the reading and writing operation. The reading operation of the
      MRAM with different sensing schemes and cell array structures is discussed, in
      particular the reference resistance generating schemes which are introduced to
      maximize the cell efficiency and reading reliability. The high density, low cost
      cross-point cell layout structures are analyzed systematically. The writing
      operation modes ranging from the half-select, toggle mode, guided SAF direct
      writing, thermally assisted writing, to the spin transfer switching are
      investigated both theoretically and experimentally. The thermal factor always
      plays an important role in determine not only the thermal stability but also the
      reading and writing reliability.

PMID- 17455480
TI  - Molecular memory based on nanowire-molecular wire heterostructures.
AB  - This article reviews the recent research of molecular memory based on self
      assembled nanowire-molecular wire heterostructures. These devices exploit a novel
      concept of using redox-active molecules as charge storage flash nodes for
      nanowire transistors, and thus boast many advantages such as room-temperature
      processing and nanoscale device area. Various key elements of this technology
      will be reviewed, including the synthesis of the nanowires and molecular wires,
      and fabrication and characterization of the molecular memory devices. In
      particular, multilevel memory has been demonstrated using In2O3 nanowires with
      self-assembled Fe-bis(terpyridine) molecules, which serve to multiple the charge
      storage density without increasing the device size. Furthermore, in-depth studies
      on memory devices made with different molecules or with different
      functionalization techniques will be reviewed and analyzed. These devices
      represent a conceptual breakthrough in molecular memory and may work as building
      blocks for future beyond-CMOS nanoelectronic circuits.

PMID- 17455481
TI  - Defect-tolerant architectures for nanoelectronic crossbar memories.
AB  - We have calculated the maximum useful bit density that may be achieved by the
      synergy of bad bit exclusion and advanced (BCH) error correcting codes in
      prospective crossbar nanoelectronic memories, as a function of defective memory
      cell fraction. While our calculations are based on a particular ("CMOL") memory
      topology, with naturally segmented nanowires and an area-distributed nano/CMOS
      interface, for realistic parameters our results are also applicable to "global"
      crossbar memories with peripheral interfaces. The results indicate that the
      crossbar memories with a nano/CMOS pitch ratio close to 1/3 (which is typical for
      the current, initial stage of the nanoelectronics development) may overcome
      purely semiconductor memories in useful bit density if the fraction of nanodevice
      defects (stuck-on-faults) is below approximately 15%, even under rather tough, 30
      ns upper bound on the total access time. Moreover, as the technology matures, and
      the pitch ratio approaches an order of magnitude, the crossbar memories may be
      far superior to the densest semiconductor memories by providing, e.g., a 1
      Tbit/cm2 density even for a plausible defect fraction of 2%. These highly
      encouraging results are much better than those reported in literature earlier,
      including our own early work, mostly due to more advanced error correcting codes.

PMID- 17455482
TI  - Power dissipation in spintronic devices: a general perspective.
AB  - Champions of "spintronics" often claim that spin based signal processing devices
      will vastly increase speed and/or reduce power dissipation compared to
      traditional 'charge based' electronic devices. Yet, not a single spintronic
      device exists today that can lend credence to this claim. Here, I show that no
      spintronic device that clones conventional electronic devices, such as field
      effect transistors and bipolar junction transistors, is likely to reduce power
      dissipation significantly. For that to happen, spin-based devices must forsake
      the transistor paradigm of switching states by physical movement of charges, and
      instead, switch states by flipping spins of stationary charges. An embodiment of
      this approach is the "single spin logic" idea proposed more than 10 years ago.
      Here, I revisit that idea and present estimates of the switching speed and power
      dissipation. I show that the Single Spin Switch is far superior to the Spin Field
      Effect Transistor (or any of its clones) in terms of power dissipation. I also
      introduce the notion of "matrix element engineering" which will allow one to
      switch devices without raising and lowering energy barriers between logic states,
      thereby circumventing the kTln2 limit on energy dissipation. Finally, I briefly
      discuss single spin implementations of classical reversible (adiabatic) logic.

PMID- 17455483
TI  - MEMS-based probe recording technology.
AB  - This paper reviews the recent developments in the area of MEMS-based probe
      recording technology. Various state-of-the-art scanning probe microscope (SPM)
      based techniques are briefly introduced, followed by the description of system
      approaches of MEMS-based probe recording technology and the basic MEMS-based
      actuation mechanism. Subsequently, current research status in developing MEMS
      based probe recording technology with emphasis on storage architecture, MEMS
      access systems, probe recording mechanisms, and media for terabit per square inch
      recording density, is reviewed. Lastly, potential research topics and prospects
      for MEMS-based probe recording technology development are discussed.

PMID- 17455484
TI  - Silicon nanocrystal memories: a status update.
AB  - In the last decade, the silicon nanocrystal memory technology has received
      widespread interests from the scientific community working in the field of non
      volatile solid-state memories, considering it as a feasible candidate for the
      post-Flash scenario. The immunity to stress-induced leakage current and the
      reduction of parasitic floating-gate capacitive couplings make the nanocrystal
      technology very attractive, especially when considering the CMOS compatible
      process flow. However, many open issues still exist for its development, first of
      all concerning its scaling perspectives. Starting from the discussion of the
      basic principles of nanocrystal storage, in this paper we review the major
      benefits and the open challenges of the silicon nanocrystal memory technology.

PMID- 17455485
TI  - FePt nanocluster films for high-density magnetic recording.
AB  - High anisotropy L1(0) ordered FePt thin films are considered to have high
      potential for use as high areal density recording media, beyond 1 Tera bit/in2.
      In this paper, we review recent results on the synthesis and magnetic properties
      of L1(0) FePt nanocomposite films. Several fabrication methods have been
      developed to produce high-anisotropy FePt films: epitaxial and non-epitaxial
      growth of (001)-oriented FePt:X (X = Au, Ag, Cu, C, etc.) composite films that
      might be used for perpendicular media; monodispersed FePt nanocluster-assembled
      films grown with a gas-aggregation technique and having uniform cluster size and
      narrow size distribution; self-assembled FePt particles prepared with chemical
      synthesis by reduction/decomposition techniques, etc. The magnetic properties are
      controllable through variations in the nanocluster properties and nanostructure.
      FePt and related films show promise for development as heat-assisted magnetic
      recording media at extremely high areal densities. The self-assembled FePt arrays
      show potential for approaching the ultimate goal of single-grain-per-bit
      patterned media.

PMID- 17455486
TI  - Fabrication of magnetic nanodot arrays for patterned magnetic recording media.
AB  - Fabrication processes of arrayed magnetic nanodots for the use of patterned
      magnetic recording media were reviewed. One candidate for the patterned media is
      ordered assemble of magnetic nanoparticles, and the other is patterned magnetic
      thin films fabricated using various micro/nano scale machining processes. For the
      formation of patterned masks and molds, lithography processes as well as self
      organized pattern formation are utilized. For the deposition processes of
      magnetic dots, electrochemical deposition processes were widely used. These
      fabrication processes are reviewed mainly from recent reports. The recording
      systems for the patterned media including probe-type-recording are also
      overviewed.

PMID- 17455487
TI  - Optical response of photopolymer materials for holographic data storage
      applications.
AB  - We briefly review the application of photopolymer recording materials in the area
      of holographic data storage. In particular we discuss the recent development of
      the Non-local Polymerisation Driven Diffusion model. Applying this model we
      develop simple first-order analytic expressions describing the spatial frequency
      response of photopolymer materials. The assumptions made in the derivation of
      these formulae are described and their ranges of validity are examined. The
      effects of particular physical parameters of a photopolymer on the material
      response are discussed.

PMID- 17455489
TI  - Surface morphology of epitaxial magnetic tunnel junctions.
AB  - The surface morphology of epitaxial Fe(001)/MgO(001)/Fe(001) magnetic tunnel
      junctions, which show the giant tunneling magnetoresistance effect, was
      investigated by in situ scanning tunneling microscopy. It was observed that an
      epitaxial MgO barrier layer forms flat surface structures. The surface was
      flatter with distinct steps and terraces after annealing, which would lead to an
      increase of the tunneling magnetoresistance ratio. Examination of the local
      electronic structures of 1.05-nm-thick MgO barrier layers by scanning tunneling
      spectroscopy revealed no pinholes in the layers, so they would be perfect
      barriers in magnetic tunnel junctions.

PMID- 17455488
TI  - Physics of perpendicular recording with a patterned soft underlayer.
AB  - In this paper, it is argued that perpendicular recording in the most popular
      current form--with the use of a continuous soft underlayer (SUL)--may not be the
      most optimal way to maximize the achievable areal density. As a possible
      solution, patterning of SUL is discussed. The purpose of patterning of a SUL is
      to effectively move the image head closer to the recording media, as compared to
      the real recording head, and thus increase the net recording field and the field
      gradient across the thickness of the media. Various patterning configurations and
      combinations with recording layers are comparatively studied. It is illustrated
      that with a patterned SUL, the recording and sensitivity fields, responsible for
      writing and reading information, respectively, could be not only increased by
      several factors but also localized across the entire thickness of the recording
      media.

PMID- 17455490
TI  - Manipulating spin current in the magnetic nanopillar.
AB  - Because of the capability to switch the magnetization of a nanoscale magnet, the
      spin transfer effect is critical for the application of magnetic random access
      memory. For this purpose, it is important to enhance the spin current carried by
      the charge current. Calculations based on the diffusive spin-dependent transport
      equations reveal that the magnitude of spin current can be tuned by modifying the
      ferromagnetic layer and the spin relaxation process in the device. Increasing the
      ferromagnetic layer thickness is found to enhance both the spin current and the
      spin accumulation. On the other hand, a strong spin relaxation in the capping
      layer also increases the spin current but suppresses the spin accumulation. To
      demonstrate the theoretical results, nanopillar structures with the size of
      approximately 100 nm are fabricated and the current-induced magnetization
      switching behaviors are experimentally studied. When the ferromagnetic layer
      thickness is increased from 3 nm to 20 nm, the critical switching current for the
      current-induced magnetization switching is significantly reduced, indicating the
      enhancement of the spin current. When the Au capping layer with a short spin
      diffusion length replaces the Cu capping layer with a long spin-diffusion length,
      the reduction of the critical switching current is also observed.

PMID- 17455491
TI  - Tuning the exchange bias in NiFe/Fe-oxide bilayers by way of different Fe-oxide
      based mixtures made with an ion-beam deposition technique.
AB  - We have investigated the structural and magnetic properties of ion-beam deposited
      polycrystalline NiFe (25 nm)/Fe-oxide (35 nm) bilayers. A film prepared with an
      assist beam O2 to Ar gas ratio of 0% during deposition had a bottom layer that
      consisted of pure b.c.c. Fe (a = 2.87 A) whereas films prepared with 19%O2/Ar and
      35%O2/Ar had either Fe3O4 (a = 8.47 angstroms) or alpha-Fe2O3 (a = 5.04
      angstroms, c = 13.86 angstroms) bottom layers, respectively. Cross-sectional
      transmission electron microscopy revealed a smooth interface between the top nano
      columnar NiFe and bottom nano-columnar Fe-oxide layer for all films. At room
      temperature, the observed coercivity (Hc approximately 25 Oe) for a film prepared
      with 19% O2/Ar indicates the existence of a magnetically hard ferrimagnetic Fe3O4
      phase that is enhancing the plain NiFe (Hc approximately 2 Oe) by way of exchange
      coupling. A significant amount of exchange bias is observed below 50 K, and at 10
      K the size of exchange bias hysteresis loops shift increases with increasing
      oxygen in the films. Furthermore, the strongest exchange coupling (H(ex)
      approximately 135 Oe at 10 K) is with alpha-Fe2O3 (35% O2/Ar) as the bottom film
      layer. This indicates that the pure antiferromagnetic phases work better than
      ferrimagnetic phases when in contact with ferromagnetic NiFe. H(ex) (T) is well
      described by an effective AF domain wall energy that creates an exchange field
      with a (1 - T/T(crit)) temperature dependence. Hc (T) exhibits three distinct
      regimes of constant temperature that may indicate the existence of different AF
      spin populations that couple to the FM layer at different temperatures.

PMID- 17455492
TI  - Self-organized magnetic nanowire arrays based on alumina and titania templates.
AB  - Densely packed arrays of magnetic nanowires have been synthesized by
      electrodeposition filling of nanopores in alumina and titania membranes formed by
      self-assembling during anodization process. Emphasis is made on the control of
      the production parameters leading to ordering degree and lattice parameter of the
      array as well as nanowires diameter and length. Structural, morphological and
      magnetic properties exhibited by nanowire arrays have been studied for several
      nanowire compositions, different ordering degree and for different nanowire
      aspect ratios. The magnetic behaviour of nanowires array is governed by the
      balance between different energy contributions: shape anisotropy of individual
      nanowires, the magnetostatic interaction of dipolar origin among nanowires, and
      magnetocrystalline and magnetoelastic anisotropies induced by the pattern
      templates. These novel nanocomposites, based on ferromagnetic nanowires embedded
      in anodic nanoporous templates, are becoming promising candidates for
      technological applications such as functionalised arrays for magnetic sensing,
      ultrahigh density magnetic storage media or spin-based electronic devices.

PMID- 17455493
TI  - Nanolubrication: patterned lubricating films using ultraviolet (UV) irradiation
      on hard disks.
AB  - Nanolubrication is emerging to be the key technical barrier in many devices. One
      of the key attributes for successful device lubrication is self-sustainability
      using only several molecular layers. For single molecular species lubrication,
      one desires bonding strength and molecular mobility to repair the contact by
      diffusing back to the contact. One way to achieve this is the use of mask to
      shield the surface with a patterned surface texture, put a monolayer on the
      surface and induce bonding. Then re-deposit mobile molecules on the surface to
      bring the thickness back to the desired thickness. This paper describes the use
      of long wavelength UV irradiation (320-390 nm) to induce bonding of a
      perfluoropolyether (PFPE) on CN(x) disks for magnetic hard disk application. This
      allows the use of irradiation to control the degree of bonding on CN(x) coatings.
      The effect of induced bonding based on this wavelength was studied by comparing
      100% mobile PFPE, 100% bonded PFPE, and a mixture of mobile and bonded PFPE in a
      series of laboratory tests. Using a lateral force microscope, a diamond-tipped
      atomic force microscope, and a ball-on-inclined plane apparatus, the friction and
      wear characteristics of these three cases were obtained. Results suggested that
      the mixed PFPE has the highest shear rupture strength.

PMID- 17455494
TI  - Toward understanding the mechanism of nonlinear optical characteristics of PbTe
      thin film for nano-optical memory.
AB  - An experimental study is conducted toward understanding the mechanism of
      nonlinear optical properties of PbTe thin film that were demonstrated potentially
      usable for nano-optical memory based on super-resolution technology. By way of a
      real time optical-electrical characterization of a PbTe thin film device, it is
      found that absorption coefficient decreases with increasing laser power,
      accompanied by increase in carrier concentration. From z-scan measurements,
      nonlinear optical coefficient due to a long pulse (1 micros) z-scan is found
      nearly 3 order of magnitude higher than the one due to a short pulse (30 ps) z
      scan when input energy density is relatively comparable. Conceivably, these
      experimental findings call for a physical model that is able to account for the
      prevailing role of a thermal contribution within the framework of absorption
      saturation by band filling. We speculate that the absorption saturation might be
      enhanced dramatically by making various indirect interband transitions possible
      via participation of phonons in a photonic excitation process.

PMID- 17455495
TI  - Simulation-based comparison of cell design concepts for phase change random
      access memory.
AB  - The RESET operation of different design concepts for phase change random access
      memory (PCRAM) cell is studied and compared using a three dimensional simulation
      model. This numerical algorithm comprises four interacting sub-models, which
      describe the electrical, thermal, phase change, and percolation dynamics in the
      PCRAM devices during the switching operation. The so-called vertical, confined,
      and lateral cell geometries are evaluated in terms of their current requirements
      for RESET operations, which is one of the most critical issues for an achievement
      of high integration densities. The advantages of the confined and lateral cell
      architecture as compared to the conventional vertical cell concept are explored,
      demonstrating their benefits of advanced thermal management and minimized current
      defined area. The simulation results agree well with experimental features of the
      RESET operation for the PCRAM design concepts studied.

PMID- 17455496
TI  - Two-dimensional ultrahigh-density X-ray optical memory.
AB  - Most important aspect of nanotechnology applications in the information ultrahigh
      storage is the miniaturization of data carrier elements of the storage media with
      emphasis on the long-term stability. Proposed two-dimensional ultrahigh-density X
      ray optical memory, named X-ROM, with long-term stability is an information
      carrier basically destined for digital data archiving. X-ROM is a semiconductor
      wafer, in which the high-reflectivity nanosized X-ray mirrors are embedded. Data
      are encoded due to certain positions of the mirrors. Ultrahigh-density data
      recording procedure can e.g., be performed via mask-less zone-plate-array
      lithography (ZPAL), spatial-phase-locked electron-beam lithography (SPLEBL), or
      focused ion-beam lithography (FIB). X-ROM manufactured by nanolithography
      technique is a write-once memory useful for terabit-scale memory applications, if
      the surface area of the smallest recording pits is less than 100 nm2. In this
      case the X-ROM surface-storage capacity of a square centimetre becomes by two
      orders of magnitude higher than the volumetric data density really achieved for
      three-dimensional optical data storage medium. Digital data read-out procedure
      from proposed X-ROM can e.g., be performed via glancing-angle incident X-ray
      micro beam (GIX) using the well-developed X-ray reflectometry technique. In
      presented theoretical paper the crystal-analyser operating like an image
      magnifier is added to the set-up of X-ROM data handling system for the purpose
      analogous to case of application the higher numerical aperture objective in
      optical data read-out system. We also propose the set-up of the X-ROM readout
      system based on more the one incident X-ray micro beam. Presented scheme of two
      beam data handling system, which operates on two mutually perpendicular well
      collimated monochromatic incident X-ray micro beams, essentially increases the
      reliability of the digital information read-out procedure. According the graphs
      of characteristic functions presented in paper, one may choose optimally the
      incident radiation wavelength, as well as the angle of incidence of X-ray micro
      beams, appropriate for proposed digital data read-out procedure.

PMID- 17455497
TI  - Ge quantum dot memory structure with laterally ordered highly dense arrays of Ge
      dots.
AB  - This work was devoted to the development of a Ge quantum dot memory structure of
      a MOSFET type with laterally ordered Ge quantum dots within the gate dielectric
      stack. Lateral ordering of the Ge dots was achieved by the combination of the
      following technological steps: (a) use of a focused ion beam (FIB) to create
      ordered two-dimensional arrays of regular holes on a field oxide on the silicon
      substrate, (b) chemical cleaning and restoring of the Si surface in the holes,
      (c) further oxidation to transfer the pattern from the field oxide to the silicon
      substrate, (d) removal of the field oxide and thermal re-oxidation of the sample
      in order to create a tunneling oxide of homogeneous thickness on the patterned
      silicon surface, and (e) self-assembly of the two-dimensional arrays of Ge dots
      on the patterned tunneling oxide. The charging properties of the obtained memory
      structure were characterized by electrical measurements. Charging of the Ge
      quantum dot layer by electrons injected from the substrate resulted in a large
      shift in the capacitance-voltage curves of the MOS structure. Charges were stored
      in deep traps in the charging layer, and consequently the erasing process was
      difficult, resulting in a limited memory window. The advantages of controlled
      positioning of the quantum dots in the charging layer will be discussed.

PMID- 17455498
TI  - Experimental study of single-electron phenomena in silicon nanocrystal memories.
AB  - In this paper we present experimental evidence for single-electron phenomena in
      solid-state memories based on silicon nanocrystals as storage elements. The
      stepwise evolution of the channel current of a written memory cell biased in the
      subthreshold regime is monitored by means of a purposely designed low noise
      acquisition system with a bandwidth of 1 kHz. Each channel current step-up is
      ascribed to a single-electron emission from the silicon nanocrystal to the
      silicon substrate and each current step-down is ascribed to a single-electron
      capture from the silicon substrate into the silicon nanocrystal. The effect of
      the measurement system bandwidth on the detection of single-electron events is
      discussed and a procedure for extracting the threshold voltage shift associated
      to these events is proposed. It is shown that single-electron charging and
      discharging events in a memory cell with an area of 4.5 x 10(-10) cm2 can cause
      threshold voltage shift at room-temperature of the order of several millivolts.
      Qualitative explanation for the observed threshold voltage shift distribution is
      given.

PMID- 17455499
TI  - Performance of silicon nanocrystal non-volatile memory devices under various
      programming mechanisms.
AB  - Non-volatile memory devices based on silicon nanocrystal synthesized with very
      low energy Si+ implantation are fabricated. Memory performance under various
      programming mechanisms including Fowler-Nordheim (FN), drain-bias channel-hot
      electron (DCHE), and source-bias channel-hot-electron (SCHE) has been
      investigated. It is observed that the DCHE yields the largest memory window among
      the three programming mechanisms. The DCHE and SCHE have similar endurance
      characteristics, but the SCHE has a longer retention time than the DCHE. Both the
      DCHE and SCHE have a larger memory window, a better endurance and a longer
      retention time as compared to the FN. Explanations to the phenomena are given.

PMID- 17455500
TI  - Charge-trapping effects caused by ammonia in carbon nanotubes.
AB  - Hysteretic behaviors caused by low-concentration ammonia gas are found in single
      walled carbon nanotube based field-effect transistors. The transfer curves are
      found to shift towards negative gate voltage when the gate voltage is swept
      forwardly upon introducing ammonia. In contrast, no significant change in the
      transfer curves is observed for the backward sweeping of the gate voltage. This
      phenomenon is repeatable even after the devices are annealed in dry air at 200
      degrees C for 2 hrs. Our findings can be interpreted in terms of additional
      charge traps induced by the adsorbed ammonia molecules. The observed hysteretic
      behavior enables the devices to work as memory cells, in which the carbon
      nanotube field-effect transistors act as readout and ammonia molecules play roles
      of charge storage.

PMID- 17455501
TI  - Nonvolatile memory devices with NiSi2/CoSi2 nanocrystals.
AB  - Metal-oxide-semiconductor structures with NiSi2 and CoSi2 nanocrystals embedded
      in the SiO2 layer have been fabricated. A pronounced capacitance-voltage
      hysteresis was observed with a memory window about 1 V under low programming
      voltage. The retention characteristic can be improved by using HfO2 layer as
      control oxide. The processing of the structure is compatible with the current
      manufacturing technology of semiconductor industry.

PMID- 17455502
TI  - Field dependence of switching currents in an exchange biased spin valve.
AB  - Current induced magnetic reversal due to spin transfer torque is a promising
      candidate in advanced information storage technology. It has been intensively
      studied. This work reports the field-dependence of switching-currents for current
      induced magnetization switching in a uncoupled nano-sized cobalt-based spin valve
      of exchange biased type. The dependency is investigated in hysteretic regime at
      room temperature, in comparison with that of a trilayer simple spin valve. In the
      simple spin valve, the switching currents behave to the positive and the negative
      applied magnetic field symmetrically. In the exchange biased type, in contrast,
      the switching currents respond to the negative field in a quite unusual and
      different manner than to the positive field. A negative magnetic field then can
      shift the switching-currents into either negative or positive current range,
      dependently on whether a parallel or an antiparallel state of the spin valve was
      produced by that field. This different character of switching currents in the
      negative field range can be explained by the effect of the exchange bias pinning
      field on the spin-polarizer (the fixed Co layer) of the exchange biased spin
      valve. That unidirectional pinning filed could suppress the thermal magnetization
      fluctuation in the spin-polarizer, leading to a higher spin polarization of the
      current, and hence a lower switching current density than in the simple spin
      valve.

PMID- 17455503
TI  - Synthesis and magnetic properties of FePt nanoparticles with hard nonmagnetic
      shells.
AB  - Chemically synthesized FePt nanoparticles were coated with nonmagnetic SiO2 and
      MnO shells by sol-gel and polyol processes. TEM images show that the FePt/SiO2
      nanoparticles exhibit a thick spherical shell. The size and morphology of the MnO
      shell can be controlled by changing the reaction temperature, the molar ratio of
      surfactants/Mn(acac)2, and/or the concentration of precursor. The morphology of
      the MnO shell can be either spherical-like or cubic-like, depending on whether
      the molar ratio of surfactants/Mn(acac)2 is less than or larger than 2. From XRD
      measurements, the spherical core/shell nanoparticles exhibit 3D random
      crystallographic orientation, while the cubic core/shell nanoparticles prefer
      (200) texture. The magnetic moment of FePt particles can be enhanced by coating
      with SiO2 and MnO shells. Furthermore, the agglomeration of FePt particles upon
      the thermal annealing can be significantly inhibited with SiO2 and MnO shells.

PMID- 17455504
TI  - Iron oxide shell as the oxidation-resistant layer in SmCo5 @ Fe2O3 core-shell
      magnetic nanoparticles.
AB  - This paper presents a synthesis of magnetic nanoparticles of samarium cobalt
      alloys and the use of iron oxide as a coating layer to prevent the rapid
      oxidation of as-made Sm-Co nanoparticles. The colloidal nanoparticles of Sm-Co
      alloys were made in octyl ether using samarium acetylacetonate and dicobalt
      octacarbonyl as precursors in a mixture of 1,2-hexadecanediol, oleic acid, and
      trioctylphosphine oxide (TOPO). Such Sm-Co nanoparticle could be readily oxidized
      by air and formed a CoO antiferromagnetic layer. Exchange biasing was observed
      for the surface oxidized nanoparticles. In situ thermal decomposition of iron
      pentacarbonyl was used to create iron oxide shells on the Sm-Co nanoparticles.
      The iron oxide shell could prevent Sm-Co nanoparticles from rapid oxidation upon
      the exposure to air at ambient conditions.

PMID- 17455505
TI  - Optical features of noble-metal-oxide thin films under irradiation of blue laser.
AB  - The optical reflectance and transmittance of Platinum oxide (PtO(x)) and
      palladium oxide (PdO(x)) thin films for ultrahigh-density optical storage are
      investigated using Z-scan technique under irradiation of blue laser (442 nm). The
      power thresholds of the PtO(x) and PdO(x) decomposition, 3.1 mW and 2.6 mW, are
      obtained respectively; the PtO(x) (PdO(x)) thin film is reversible and
      irreversible when input power is less than and more than 3.1 mW (2.6 mW).
      Deformation analyses by using an atom force microscope (AFM), which is formed in
      the micro irradiation region of surface on the thin film samples due to
      decomposition of the PtO(x) or PdO(x) driving the Z-scan, agree well with the Z
      scan results. The optical features obtained at 442-nm wavelength are compared
      with those at 532-nm wavelength, and the threshold difference between the two
      wavelengths is also analysed in detail based on wavelength-dependent average
      power density and wavelength-selected absorption of the thin films.

PMID- 17455506
TI  - Two-silicon-nanocrystal layer memory structure with improved retention
      characteristics.
AB  - It was demonstrated in the literature that the use of self-aligned doubly-stacked
      Si dots improves retention characteristics of a nanocrystal memory. In this
      paper, we show that a similar effect may be obtained by using two distinct layers
      of silicon nanocrystals within the gate dielectric of the MOS structure, if the
      nanocrystal density in each layer is high enough (above 10(12) dots/cm2) so as to
      get an average effect of at least one smaller dot underneath each larger one. The
      relative distance of the layers and their position from the silicon substrate and
      the gate metal are critical for optimum memory operation. Two different double
      nanocrystal-layer structures were investigated. In the first structure the two
      nanocrystal layers were close together and they were composed of dots of
      different size (lower layer: 3 nm, upper layer: 5 nm), while in the second
      structure the dot layers were composed of dots of equal diameter (d = 3 nm) and
      their inter-distance was much larger. In both cases, the retention
      characteristics of the structure were improved compared with a single dot layer
      structure. In the second case this improvement was significantly larger than in
      the first case. Extrapolation of the data to ten years memory operation, showed
      that the charge loss after this time was only approximately 12%.

PMID- 17455507
TI  - Optothermal property and decomposition characteristics of PtO(x) ultrathin film
      sandwiched between ZnS-SiO2 for super-resolution near-field recording.
AB  - We have investigated the optothermal property and decomposition characteristics
      of PtO(x) ultrathin film protected by ZnS-SiO2 layers and effects of the
      constituent phases of PtO(x) on super-resolution capability and read stability of
      the super-RENS disk. All the ZnS-SiO2/PtO(x)/ZnS-SiO2 multilayers exhibited a
      steep reflectivity drop at the temperature range between 265 and 350 degrees C,
      corresponding to the decomposition of PtO(x). The decomposition temperature of
      the 4-nm-thick PtO(x) ultrathin film protected by ZnS-SiO2 layers was much lower
      than those obtained in thick PtO(x) films without protection. The activation
      energy for thermal decomposition was approximately 1.3 eV. Both the decomposition
      temperature and activation energy for thermal decomposition were unaffected by
      the constituent phases of PtO(x). Carrier to noise ratios (CNR) of over 40 dB for
      mark size of 150 nm were achieved in all super-resolution near-field structure
      (super-RENS) disks, while the super-resolution readout was limited to 2.5 x 10(3)
      approximately 4.5 x 10(4) cycles. The effect of constituent phases of PtO(x) on
      the super-resolution capability of super-RENS disk with a PtO(x) mask layer was
      minimal. However, as the constituent phases of PtO(x) mask layer transformed from
      a mixture of Pt and PtO, to pure PtO, and then to a mixture of PtO and PtO2, the
      readout stability of super-RENS disk increased dramatically since less heat was
      absorbed by the PtO(x) mask layer composed of PtO and PtO2 during the readout
      process, prohibiting the diffusion of materials inside the bubble to the GeSbTe
      phase change layer.

PMID- 17455508
TI  - Statistical study of effective anisotropy field in ordered ferromagnetic nanowire
      arrays.
AB  - Soft ferromagnetic nanowire arrays were obtained by electrodeposition of Co-Fe-P
      alloy into the pores of high quality home-made anodized aluminum oxide (AAO)
      templates. Bath acidity and current density were the two parameters used in order
      to tailor the orientation of local anisotropy axes in individual nanowires. In
      order to quantify the influence of the induced anisotropies on the magnetization
      processes in individual nanowires, the in-plane magnetization loops of the arrays
      are modeled as log-normal distributions of Stoner-Wohlfarth transverse
      magnetization processes. Using the lognormal mean parameter as an approximation
      for the saturation applied field of the array, we compute the effective
      anisotropy of the nanowires, which is found to increase with the pH of the
      electrodeposition bath.

PMID- 17455509
TI  - Prescribing proposals need backing.

PMID- 17455510
TI  - 'Services for people with dementia are not meeting families' expectations'.

PMID- 17455511
TI  - Join forces against infection.

PMID- 17455512
TI  - Putting agency nursing in the spotlight. Interview by Nic Paton.

PMID- 17455513
TI  - Managing the increasing incidence of tuberculosis.

PMID- 17455514
TI  - Reproductive system part two--male physiology and function.

PMID- 17455515
TI  - Management of severe mental illness and substance misuse.
AB  - Growing numbers of people suffering from severe mental illness (SMI) have a
      coexisting substance use disorder (SUD)--this is increasingly termed dual
      diagnosis or SMISUD. This article outlines the prevalence and the complexity of
      the condition, as well as assessment and care planning.

PMID- 17455516
TI  - Faecal incontinence following childbirth.

PMID- 17455517
TI  - Encopresis in children with learning disabilities.

PMID- 17455518
TI  - The experience of living with faecal incontinence.

PMID- 17455519
TI  - 'Is complementary medicine a science'?

PMID- 17455520
TI  - [Severe infections within the upper extremity--analysis of the causes and methods
      of treatment].
AB  - INTRODUCTION: Infections within the upper extremity can be a cause of serious
      problems when not treated early and adequately. Apparently looking innocuous at
      the beginning, infection can spread through synovial sheath of the tendons from
      finger to the hand, wrist and forearm finally developing phlegmone of the upper
      limb. The objective of the study was to review the methods of treatment of deep
      infections of the upper limb and to analyse the causes of severity. PATIENTS AND
      METHODS: Thirty-seven patients with deep infections within upper limb were
      identified in the Department over the period of 1999-2005. Patients included 28
      men and 9 women in mean age of 50 years. The delay between initial event and
      referral to hospital was mean of 12 days (range 2-62). The most common cause was
      superficial contusion of the hand--13 patients, small wound of the hand--8 and
      bite--6 patients. In 14 cases infection was localised in the finger (felon), in
      23 patients within the hand, wrist, forearm or arm. In 6 of these 23 patients
      whole distal part of the extremity, from finger to the forearm was involved. All
      patients were operated on under regional anaesthesia with the use of tourniquet.
      Several wide incisions were performed, pus and necrotic tissues were removed and
      wounds were further managed in the open manner. Antibiotic therapy was used in
      all cases. RESULTS: A staphylococcus aura was the most common precipitating
      organism, found in 271 of 30 patients (90%). In 5 patients (13%) infection was so
      deep that resulted in necrosis and amputation was necessary. Amputation of the
      single finger was performed in 3 patients, an amputation of 3 fingers was
      necessary in one patient, and other one lost whole forearm. Healing of the wounds
      was facilitated by secondary suture, skin grafts and pedicled flaps in 17 cases.
      Mean time of stay in the hospital was 7 days (range 4-38). The most common causes
      of development of severe infections were ignorance of GPs who treated too long
      superficial infections, and stupidity of the patients themselves who delayed
      visit the doctor until infection became extremely severe. CONCLUSION: The
      following algorithm in the treatment of infections of the upper extremity:
      operation under adequate anesthesia and in bloodless field, wide incisions,
      drainage, and early mobilization of the limb, in our opinon reduces risk of the
      amputation and severe functional impairment of the hand.

PMID- 17455521
TI  - [Evaluation of hand function and symptom severity among patients after endoscopic
      carpal tunnel release].
AB  - The aim of the study was to evaluate function of hand and symptom severity after
      endoscopic carpal tunnel release. The examined material in this study comprises
      45 patients (56) hands operated with single-portal endoscopic method. In order to
      evaluation outcomes of treatment Carpal Tunnel Syndrome Symptom Severity Scale
      (CTS SSS), Carpal Tunnel Syndrome Functional Status Scale (CTS FSS) and clinical
      examinations outcomes were used. Average results of preoperative questionnaires
      were equaled respectively: CTS SSS--2.9 and CTS FSS--2.8. Average results of
      postoperative questionnaires were equaled respectively: CTS SSS--1.5 and CTS FSS-
      1.7. Statistical analysis has shown significantly better results of CTS SSS and
      CTS FSS questionnaires, among patients with positive Tinel's Test and without
      thenar atrophy found before operation. Results of research based on
      questionnaires and clinical examinations, proved fast return of function of hand
      and decrease symptoms severity after endoscopic carpal tunnel release.

PMID- 17455522
TI  - [Assessment of results of opponensplasty by transfer of flexor digitorum
      superfitcialis tendon of the ring finger].
AB  - This study is the review of 16 hands in the same number of patients (15 men, 1
      female) in whom ring finger flexor digitorum superficialis opponensplasty was
      performed. The patients were operated on during the period of 6 years. The lack
      of thumb opposition was a result of traumatic nerve leasions (5 median, 11 median
      and ulnar). The operation was performed 7.2 months (on average) after the nerve
      reconstruction. The outcome was assessed by scoring the finger to which the thumb
      could obtain a pinch grip (Kapandji's test), measuring the gap between thumb and
      little finger MCP joints, the patient's satisfaction. The sensitivity on the
      pulps of ring and little finger were also tested. Two patients were reoperated
      for loosening the transferred tendon, two patients developed minor dysfunction of
      the donor finger. The results were evaluated 41 weeks after an operation. As a
      result of the operation the "opposition gap" was diminished by 22 mm on average;
      the patients scoring by Kapandji's test was improved by 2 points. Eight patients
      assessed the improvement of the hand function as excellent, six as good, two were
      dissatisfied with the result.

PMID- 17455523
TI  - [Clinical and therapeutical implications of molecular aspects of Dupuytren's
      disease pathogenesis].
AB  - Etiology and pathogenesis of Dupuytren's disease still remains unclear. This
      disease like other conditions resulting from chronic pathological fibrosis (organ
      fibromatoses, intraperitoneal adhesions, hypertrophic scars) remains a
      therapeutic problem. These facts substantiate fully research on processes leading
      to pathological changes in these diseases. The ongoing research is not only to
      broaden our knowledge but mainly to work out methods of causal treatment. Despite
      significant observations in vitro and in clinical trials, practical applications
      from these studies are still a way ahead. Consequently, symptomatic surgical
      treatment of Dupuytren's disease still remains the method of choice.

PMID- 17455524
TI  - [Evaluation of bone metabolism in patients after total hip replacement based on
      bone turnover markers].
AB  - Serum bone markers: N-mid osteocalcin (OCN-Mid) and Cross-Laps were evaluated in
      51 patients (15 men and 36 women), age 50-81y. (mean 69) with OA undergoing
      elective cemented THR. Samples were collected at the day before operation and 3
      days, 1, 2, 6 weeks, 3, 6, 12 months after the operation and markers measured by
      direct chemoluminescency using Modular E-170. Lowest values of both markers were
      noted at the 3-rd day after operation. Cross-Laps levels rose rapidly reaching
      highest levels 2 weeks after operation and still were significantly (alpha =
      0,05) elevated after 6 weeks. The highest but not statistically significant
      levels of OCN-Mid were noted after 6 months. After 12 months both markers
      returned to preoperative values. OCN-Mid/Cross-Laps ratio were lowest after 2
      weeks (maximal resorption), then rose over the preoperative value after 3 months,
      being still significantly elevated after 12 months, indicating that bone
      formation still occurred. No significant differences were found according to sex,
      radiolucencies around the endoprosthesis (14 patients) and periarticular
      ossification (9 patients). Serum bone markers can show the process of bone
      healing around endoprosthesis, but because of different basic levels of bone
      metabolism, evaluation of this process can be achieved only with comparison to
      preoperative values.

PMID- 17455525
TI  - [Serum bone markers in patients with loosening of cemented total hip
      endoprosthesis].
AB  - Serum levels of bone markers N-mid osteocalcin (OCN-Mid) and Cross-Laps in 20
      patients (8 men and 12 women) with loosening of at least one element of total hip
      endoprosthesis confirmed during operation were compared with age and sex matched
      group with OA. Marker levels were measured by direct chemoluminescency using
      Modular E-170. Statistical analysis were done with t-Student test (alpha = 0.05).
      There were no significant differences in OCN-Mid, Cross-Laps levels and OCN
      Mid/Cross-Laps ratio between both groups. Implant loosening is a slow process
      taking place on a relatively small surface in comparison to whole skeleton, so
      bone markers have no clinical value in diagnostics of total hip loosening.

PMID- 17455526
TI  - [Comparison of the Ender's nailing and Dynamic Hip Screw (DHS) fixation in the
      treatment of trochanteric fractures in elderly patients].
AB  - The aim of this study was an evaluation which operative method of treatment:
      stabilisation with the Dynamic Hip Screw or with Ender's nails is less invasive
      procedure in elderly patients with trochanteric fractures. 100 consecutive
      patients with trochanteric fracture were enrolled into the study, of which 53
      patients (49 women, 4 men; mean age 89 years) were stabilised intramedullarily
      with the use of Ender's nails and 47 patients (26 women, 21 men; mean age 76
      years) were treated operatively with the use of Dynamic Hip Screw. The factors
      compared the mean length of hospital stay, the mean duration of the surgery, post
      operative blood loss, early local and general complication rate and mortality in
      both groups. We took into account their general health and coexisting illnesses
      according to the American Society of Anesthesiologists (ASA) classification, type
      of fracture according to AO and Evan's classifications and the surgeon's
      experience. The mean duration of the surgery was 27 minutes longer in the case of
      DHS stabilisation. The complication rate was higher and the mean length of
      postoperative hospital stay was longer after Ender nailing. The mean blood loss:
      the drop in Red Blood Cells (RBC), Haematocrit (Ht) and the Mean Haemoglobin
      Concentration (Hb) was also higher in patients treated with the use of Ender
      nails. The mean rate of blood units that had to be transfused postoperatively was
      also higher in "Ender" group. The difference was statistically significant,
      especially in the group of patients treated as emergency procedure at the day of
      admission (p < 0.05). The operative treatment of trochanteric fractures in
      elderly patients with the use of DHS device showed to be a less invasive
      procedure in comparison to Ender nailing. In conclusion, the indications for this
      method of trochanteric fractures' treatment should be expanded, especially in the
      case of unstable fractures.

PMID- 17455527
TI  - [The evolution of AO/ASIF views on fracture treatment].
AB  - The evolution of AO/ASIF views on fracture treatment, which has occured within
      last 50 years, is described in the present paper. In that time AO principles has
      been changed from mechanical approach to fracture care to methods considering
      first of all the biological aspects of injury. It has been manifested in
      invention of new implants of lower affect on bone tissue and emphasizing of soft
      tissue and atraumatic surgery technique importance. Described changes were based
      on careful analysis of obtained treatment results, creation of trauma centers
      collecting the large numbers of trauma patients and on broad experimental
      researches on bone biology, it's vascularisation and healing as well as on bone
      pathology.

PMID- 17455528
TI  - [The clinical value of transpedicular thoraco-lumbar spine stabilisation].
AB  - The authors present the results of treatment of spine neoplastic disease using
      transpedicular stabilisation. The clinical material of 2004 year are 20 cases, 15
      males (75%) and 5 female (25%), 19 of them were qualified to the surgical
      treatment (95%). Obtained outcomes permit authors to make confirmation that the
      transpedicular stabilisation of thoraco-lumbar spine as a surgical treatment of
      it's neoplastic disease decrease pain, improve neurological condition if spinal
      cord damage are not durable, makes easer the rehabilitation process and nursing
      care.

PMID- 17455529
TI  - [Current concept on spine metastases management].
AB  - In the article we present the contemporary point of view on the role of operative
      treatment in metastatic lesions in spine. The malignant tumors becoming more
      often encountered lesion. Due to the index treatment and increasing survival of
      those patient the metastases are more commonly observed. Without possibilities to
      treat the cause of the neoplasm the combined treatment is the best choice.
      Operative treatment options with metastases in spine are related to the clinical
      status and live expectancy. In the modern orthopedic approach, for patient in
      good clinical condition, the aggressive operative treatment with tumor excision
      is preferred with subsequent restoration of the spine stability. This allows
      swift postoperative mobilization without additional orthotic support.

PMID- 17455530
TI  - [Congenital dislocation of the knee with forefoot--adduction deformity].
AB  - A two days newborn girl a congenital recurvatum of the right knee and bilateral
      congenital adduction of forefootwas treated in The Department of Orthopaedics in
      Gdansk. A slow correction of the knee was performed followed by cast
      immobilization. A good result was observed.

PMID- 17455531
TI  - [Treatment of metacarpal and phalangeal fractures--a review].
AB  - Isolated fractures of metacarpals and phalanges are the commonest injuries
      affected upper extremity, which constitute about 10% of skeletal fractures in
      general. They occur the most frequently in age between 10 and 40, so affect
      mostly children and young adults. Based no the literature from last two decades,
      the results of the treatment of these fractures with various methods are
      presented. Isolated and undisplaced fractures of the metacarpals and phalanges
      are usually managed conservatively using a plethora of methods of immobilization
      including elastic bandage, taping with neighbored finger, thermoplastic and
      plaster of Paris splints. Stable fractures with angular displacement require
      reduction or not, if dislocation is acceptable. Unstable and axially displaced
      fractures are usually treated operatively, however there is no enough scientific
      evidence that this option is more effective. Surgery for these fractures includes
      percutaneous fixation with K-wires introduced intramedullary or crossed, K-wires
      fixation with neighbored, unaffected metacarpal bone, open techniques such as lag
      screws and plates and external fixation. Phalangeal fractures are more frequently
      treated operatively, since they are commonly believed unstable what may result in
      malunion. The results of the treatment of fractures of metacarpals and phalanges
      are generally good, regardless the method which was used. The failures include
      nonunion, malunion which disturbs hand function or is cosmetically unacceptable,
      reduction of finger movement, degenerative changes in neighbored joints and
      algodystrophy. We stress that contemporary literature provides no evidence that
      either of the methods of the treatment of these fractures is superior, but rather
      suggests that they are equally effective. Common drawback of the quoted studies
      is lack of subjective assessment of the dexterity of the hand in daily and
      professional activity with standardized questionnaires.

PMID- 17455533
TI  - [A strategy of rehabilitation in children with proximal femoral focal deficiency
      treated with modyfied Van Nes rotationplasty].
AB  - We present a strategy of a complex rehabilitation in children with pffd before
      and after Van Nes rotationplasty. The rehabilitation proces is divided into tree
      stages: preoperative, in which general exercises, swimming etc. are used to
      improve patient's general phisical condition with special care to improve ankle
      range of motion and to strenghten the muscles: gastrocnemius, quadriceps femoris
      and glutei on the afected side. Second stage begines whith the cast removal.
      Gentle ankle manipulations, passive and in about a 0 days after the cast removal,
      active ankle movements are excercised. The last stage begins when individual
      prosthesis is made and the patient begins to learn how to stand and to walk with
      proper active "knee" flexion and extension and with proper foot progression
      angle, initialy with cruthes on flat surface, and finnally, about 3 months after
      the surgery without cruthes, also on stairs. A good cooperation with the child's
      parents and with the child itself is necessary to have a success in the
      rehabilitation process.

PMID- 17455532
TI  - [Arthroscopic Bankart repair].
AB  - Traumatic anterior shoulder instability is the most common type of shoulder
      instability. Treatment is surgical and there is no single best procedure.
      Arthroscopic Bankart repair restores stability by reattaching the labrum or
      capsule directly to the anterior glenoid rim. The aim of the study was to assess
      the clinical value of the arthroscopic Bankart repair. Between 2001 and 2005
      twenty eight patients with traumatic anterior shoulder instability were treated.
      During the operation the capsulolabral tissue was mobilized from the anterior
      glenoid rim and neck of scapula, then 3 Mitek suture anchors were inserted and
      the labrum was sutured to the anterior glenoid rim. The patients were clinically
      evaluated according to MISS questionnaire. Up till now the recurrence of the
      anterior shoulder instability were not seen in the 25 patients operated with the
      aforementioned method. MISS questionnaire values were significantly higher
      following the surgery. Arthroscopic Bankart repair restores joint stability,
      helps to avoid complications associated With opening of the shoulder and gives a
      better cosmetic effect.

PMID- 17455534
TI  - [Manual ability classification system for children with cerebral palsy].
AB  - Manual Ability Classification System provides a systematic method to classify how
      children with cerebral palsy use their hands when handling objects in daily
      activities. MACS is a subjective classification system and is based upon self
      initiated manual abilities, with a particular emphasis on handling objects in a
      individual's personal space. MACS is designed for children with cerebral palsy,
      aged 4 to 18 years.

PMID- 17455535
TI  - Heart-brain medicine: where we go from here and why.

PMID- 17455536
TI  - 'Voodoo' death revisited: the modern lessons of neurocardiology.

PMID- 17455537
TI  - The broken heart syndrome.

PMID- 17455538
TI  - Brain imaging in cardiovascular disease: state of the art.

PMID- 17455539
TI  - Cortical control of the heart.

PMID- 17455540
TI  - Neurological mechanisms of chest pain and cardiac disease.
AB  - SCS is an efficacious, reversible, and safe therapy that improves quality of
      life, increases exercise tolerance, and relieves angina pectoris, but clinical
      trials in North America are needed to confirm the data coming from Europe.
      Neuronal convergence onto STT cells underlies the referred pain associated with
      angina pectoris. With pain referred to the chest and upper arm, cardiac
      nociceptive information is transmitted via sympathetic afferent fibers to
      thoracic cells. With pain referred to the jaw and neck, cardiac nociceptive
      information is transmitted via vagal afferent fibers onto cervical cells. SCS can
      modulate the responses of thoracic STT cells to nociceptive input originating
      from the heart. SCS modulates cardiac function. It stabilizes neurons in the
      intrinsic cardiac nervous system, and can reduce infarct size via
      adrenoreceptors.

PMID- 17455541
TI  - Hypertension in sleep apnea: the role of the sympathetic pathway.

PMID- 17455542
TI  - Inflammation: implications for understanding the heart-brain connection.

PMID- 17455543
TI  - The anti-ischemic effects of electrical neurostimulation in the heart.

PMID- 17455544
TI  - The little brain on the heart.

PMID- 17455545
TI  - Open heart surgery and cognitive decline.

PMID- 17455546
TI  - The heart and the brain within the broader context of wellness.

PMID- 17455547
TI  - The heart-brain interaction during emotionally provoked myocardial ischemia:
      implications of cortical hyperactivation in CAD and gender interactions.
AB  - Mental and emotional stress can provoke transient ischemia and acute coronary
      syndrome in vulnerable patients. Furthermore, those patients so provoked are at
      increased risk for recurrent cardiac events and early death. Viable psychological
      treatments to improve prognosis exist, and preliminary trials demonstrate their
      efficacy with regard to short- and long-term outcomes, as well as economic
      savings. These findings heighten the need for efforts directed toward the
      complete identification of the differential pathophysiology of mental stress
      induced ischemia, with an eye toward development of diagnostic tests and
      establishment of risk stratification algorithms that can be applied in the
      clinical setting. Ongoing research in this vein is identifying unique aspects of
      the brain-heart relationship during mental stress that underlie the cognitive and
      emotional aspects of mental stress, and the "dow nwind" pathways by which
      distinct patterns of brain activity during mental stress can provoke otherwise
      silent myocardial ischemia. This research is making important contributions to
      the larger clinical goals associated with diagnostic testing, risk
      stratification, and treatment of patients at risk for mental stress-induced
      ischemia and poorer prognosis.

PMID- 17455548
TI  - Depression and heart disease.

PMID- 17455550
TI  - Role of the brain in ventricular fibrillation and hypertension: from animal
      models to early human studies.

PMID- 17455549
TI  - Sick at heart: the pathophysiology of negative emotions.

PMID- 17455551
TI  - New paradigms in heart-brain medicine: nonlinear physiology, state-dependent
      proteomics.

PMID- 17455552
TI  - Subarachnoid hemorrhage: a model for heart-brain interactions.

PMID- 17455553
TI  - Cardiac denervation in patients with Parkinson disease.
AB  - More than 40 neuroimaging studies have reported evidence for loss of sympathetic
      noradrenergic nerves in PD. Cardiac sympathetic denervation is virtually
      universal in patients with PD and neurogenic orthostatic hypotension. About one
      half of patients with PD who do not have orthostatic hypotension also have
      evidence for loss of noradrenergic innervation. The loss progresses over years,
      in a pattern suggesting "dying-back". Because patients with familial PD from
      mutation of the gene encoding alpha-synuclein or from triplication of the normal
      gene have low myocardial concentrations of 6-[18F]fluorodopamine-derived
      radioactivity, cardiac sympathetic denervation seems linked etiologically with
      alpha-synucleinopathy. Baroreflex-cardiovagal failure and cardiac sympathetic
      denervation can occur before onset of the movement disorder, suggesting that
      neurocardiologic testing might provide a biomarker for detecting presymptomatic
      or early PD and for following responses to putative neuroprotective treatments.

PMID- 17455554
TI  - Aging and the brain renin-angiotensin system: insights from studies in transgenic
      rats.

PMID- 17455555
TI  - Contextual cardiology: what modern medicine can learn from ancient Hawaiian
      wisdom.

PMID- 17455556
TI  - Cardiocerebral resuscitation: the optimal approach to cardiac arrest.

PMID- 17455557
TI  - Heart transplantation: a magnified model of heart-brain interactions.
AB  - The human heart transplant model unmasks the heart-brain link as an active
      process that is clinically demonstrated and confirmed at the tissue level.
      Further studies are needed to elucidate the relative contribution of each of
      these isolated observations to the pathogenesis of coronary allograft
      vasculopathy, which remains enigmatic. Recent studies have suggested that mTOR
      inhibitors may have the ability to attenuate this lethal process that limits the
      long-term survival of cardiac transplant recipients. The observations we have
      discussed here suggest that other targeted therapies, including glycoprotein
      IIb/IIIa inhibitors, tissue metalloproteinase inhibitors, and angiotensin
      receptor blockers, may facilitate the attenuation of cardiac transplant
      vasculopathy, but clinical trials are difficult to conduct in this relatively
      small population of patients. These observations may shed insight, however, into
      the pathophysiology of hypertension and its impact on the vascular system, as
      cardiac transplantation provides a setting in which heart-brain interactions are
      magnified and the pathophysiology occurs over years rather than decades.

PMID- 17455558
TI  - Patent foramen ovale and migraine.

PMID- 17455559
TI  - Patent foramen ovale and stroke: to close or not to close?

PMID- 17455560
TI  - Sudden unexplained death in epilepsy: the role of the heart.

PMID- 17455561
TI  - Hydrocephalus and the heart: interactions of the first and third circulations.
AB  - Hydrocephalus is not always caused by blockage in absorption; it can result from
      an imbalance in cardiac impulse distribution that can cause a ventriculomegaly in
      chronic communicating hydrocephalus. Chronic ventriculomegaly may result in
      cardiac dysfunction, which may beget a pathophysiologic cycle in the elderly. The
      CSF spaces play a critical role in cardiac impulse absorption: cerebral blood
      flow may be diminished in CSF disease and enhanced by its manipulation. The
      interface between the CSF circulatory system and cardiovascular system is based
      on certain organizing principles, at least one of which appears to be the control
      and regulation of cardiac impulses that are reaching the brain tissue.

PMID- 17455562
TI  - Cognitive impairment in chronic heart failure.

PMID- 17455563
TI  - Cardiac events and brain injury: ethical implications.

PMID- 17455564
TI  - [Chronic heart failure. Main symptoms: (exertional) dyspnea, orthopnea, decreased
      performance].

PMID- 17455565
TI  - [Stem cells--basic aspects and therapeutic perspectives].
AB  - Stem cells are somatic cells with different proliferation and differentiation
      potential. Embryonic stem cells (ESC) are derived from human blastocysts.
      Recently, human ESC (hESC) were generated by nuclear transfer from somatic cells
      from patients for individual cell or tissue replacement. Adult stem cells (ASC)
      are multipotent and are harvested postnatally. ASC are found in peripheral blood
      and many tissues and organs and can differentiate in vitro to many cell types and
      tissues that can be used for therapeutic purposes ("tissue engineering").
      Preliminary clinical studies demonstrate the tremendous therapeutic potential of
      ESC and ASC. Before a routine clinical application in humans, apart from many
      technical questions, safety and ethical issues need to be addressed and the
      therapeutic benefit of ESC and ASC for human diseases has to be demonstrated by
      qualified clinical studies.

PMID- 17455566
TI  - [Immunopathogenesis of viral hepatitis].
AB  - The different components of the immune system play important roles in the outcome
      of hepatitis B and C. In > 90% of HBV-infected individuals, these immune
      responses successfully clear the virus, while 50-80% of chronically HCV-infected
      individuals experience viral persistence. During the last years, the mechanisms
      of viral persistence, e.g. viral escape mutations and T cell dysfunction, have
      been characterised in more detail. The exact knowledge of the mechanisms
      contributing to viral clearance and persistence are prerequisite to the
      successful development of prophylactic and therapeutic immunostrategies.

PMID- 17455567
TI  - [Hepatocellular carcinoma: novel therapeutic approaches].
AB  - Therapeutic options for patients with hepatocellular carcinoma (HCC) are still
      limited. Only patients with small HCC are considered for curative treatment
      options such as resection, liver transplantation or local ablation. Systemic
      treatment of advanced HCC is still impaired by the high level of resistance to
      chemotherapy and irradiation. In addition, most patients with HCC are highly
      susceptible to toxic side effects due to their impaired liver function. Novel
      treatment options are based on the increasing understanding of molecular
      mechanisms involved in tumorigenesis, tumor progression and metastasis. Such
      "targeted therapies" aim at growth factors and their receptors, intracellular
      signal transduction and cell cycle control. Anti-angiogenesis targets the tumor
      vasculature. Gene therapeutic strategies are based on the transfer of therapeutic
      genes in target tissues to express highly active proteins such as suicide genes
      or cytokines. Tumor cell death by cell lysis is the mechanism of oncolytic
      viruses, which are able to selectively replicate in tumor cells. This mechanism
      may be augmented by the addition of therapeutic genes expressed by recombinant
      oncolytic viruses. The induction of a potent immune response to tumor antigens by
      vaccination strategies or by adoptive transfer of activated immune cells aim at
      the specific destruction of tumor cells by effector T-cells targeted to tumor
      antigens.

PMID- 17455568
TI  - [Innovative therapeutic approaches in endoscopy].
AB  - Within the last 25 years flexible endoscopy became the gold standard of
      intraluminal diagnostic procedures of the gastrointestinal tract. Innovative
      diagnostic techniques which might improve our facilities are real and virtual
      chromoendoscopy, optical cohearance tomography (OCT) and endomicroscopy.
      Innovative treatment options are the flexible diverticulotomy of symtomatic
      Zenker diverticula, curative treatment of early cancers of the whole GI tract,
      endoscopic antireflux treatment and even transgastric resections of different
      organs.

PMID- 17455569
TI  - Race equality and health service management: the professional interface.
AB  - The Amicus/CPHVA Equalities Committee is working to educate and support the
      workforce on equity and diversity. There is a strong focus on the race equality
      agenda. A work pack has been developed to help members challenge racism in the
      work place. It can be argued that racism remains endemic within the NHS and
      within professional employment structures. Policy and strategic development has
      so far done little to challenge the situation. Practitioners must be accountable
      for challenging their own stance on race equality and must be active in
      supporting equity within the work place.

PMID- 17455570
TI  - NICE work on good practice in mental health.

PMID- 17455571
TI  - No short cuts to good quality care for community nursery nurses (CNNs).

PMID- 17455572
TI  - The provision of primary care interventions by community health support workers
      in Pakistan.
AB  - Skill mix and role redesign have changed the face of the primary care workforce
      in the UK in recent years. In areas with minority ethnic communities, support
      workers with language skills and cultural knowledge have been employed to provide
      health care. Although this role is relatively new to the UK, countries like
      Pakistan have a long history of employing community support workers. This study
      seeks to learn from Pakistan's experience and apply the learning to the UK
      context. The findings from this study suggest that the support worker role in
      Pakistan is highly effective when training and adequate supervision is given and
      when the support worker is entrusted with a considerable degree of freedom to
      act. It was also observed that the same role might be highly effective in one
      context, but less so in another, which indicates the importance of exploring a
      range of factors that may affect outcomes. The study provided an invaluable
      opportunity to gain a better understanding of the health care system in Pakistan.
      This may assist in the development of services in the UK to improve primary
      health care, particularly for those who experience barriers in accessing
      services.

PMID- 17455573
TI  - Impetigo (ringworm).

PMID- 17455574
TI  - Mothers' perceptions of community health professional support.
AB  - This qualitative study aimed to explore mothers' experiences of the support they
      received from community health professionals. Every third mother was selected
      from an NHS Trust's database of women whose health visitors had used the Solihull
      Approach. Forty-two women were sent information packs and consent forms. Nine
      mothers who returned consent forms were interviewed. The interview transcripts
      were analysed using interpretative phenomenological analysis. The results expand
      on previous research and contribute additional ideas to the existing evidence
      base. The findings explore the concepts of trust, expertise and understanding
      within the working partnership. In addition, the results address mothers' need
      for reliability, and a preference for professionals who understood women's
      beliefs about what it means to be a 'good mother'. The results and
      recommendations are pertinent to those community health professionals who work in
      the area of early childhood intervention, including practitioners who use the
      Solihull Approach.

PMID- 17455575
TI  - Managing unwanted behaviour in pre-school children.
AB  - This paper describes a behaviour group, set up as a pilot project to empower
      parents and to promote their self-confidence in managing pre-school children's
      undesirable behaviour. Led by community nursery nurses (CNNs), the programme has
      already worked with six groups, each of six parents or carers and their children.
      Families are guided through coping strategies and learn management skills in
      changing undesirable behaviour problems in their pre-school children. Children
      between the ages of two to five years have been referred along with their parents
      to the group. Types of behaviours referred include: sleep problems,
      feeding/eating difficulties, sibling rivalry, temper tantrums, defiant anti
      social behaviour and toilet/potty training. All these behaviours are prevalent
      among pre-school children, but are sometimes difficult for parents to manage. The
      evaluation of this pilot programme was based on pre-post-programme questionnaires
      and direct observation of parent-child interaction. Success of the behaviour
      group has indicated the need for such early preventative work to continue with
      parents and children. The children's services team, which includes health
      visitors and school health advisors, refers targeted families for immediate
      intervention, without families being on a long waiting list. Parents and carers
      who have difficulties coping with their child's undesirable behaviour can now
      access a service in their local clinic. Feedback from parents has been positive.
      Such a group is also beneficial in reducing the problem of less severe
      behavioural difficulties being referred to hard pressed and understaffed CAMHS
      teams.

PMID- 17455576
TI  - The spectrum of tic disorders (2).

PMID- 17455577
TI  - Private finance initiatives (PFIs).

PMID- 17455578
TI  - Hormonal emergency contraception: a clinical primer.
AB  - Unintended and teenage pregnancies are major public health concerns in the United
      States. Emergency contraception is used to prevent pregnancy after failure of a
      contraceptive method or after unprotected intercourse. Expanded use of emergency
      contraception has the potential to reduce unintended pregnancy and induced
      abortions, while reducing state and federal healthcare expenditures. The recent
      approval of Plan B as an over-the-counter medication for individuals over 18
      years of age should improve access to this medication. However, there are still
      widespread misconceptions about the mechanisms and implications of emergency
      contraception. Expanded access to emergency contraception is associated with
      increased use, but not associated with decreased efficacy, increased sexual risk
      taking behavior, or less consistent use of traditional birth control methods.
      This review is designed to provide clinicians with information regarding the use
      of emergency contraception for reproductive age patients. It includes a brief
      description of methods of use, mechanisms of action, and side effect profiles of
      the most commonly used methods of emergency contraception, levonorgestrel and the
      Yuzpe method.

PMID- 17455579
TI  - The spectrum of staphylococcal scalded skin syndrome: case report of a four-month
      old infant.

PMID- 17455580
TI  - The outpatient use of atypical antipsychotics with Alzheimer's disease.

PMID- 17455581
TI  - A quiz on "the ethics of accepting gifts from industry".
AB  - (1) Cash payments should not be accepted from any health-related industry, which
      might create a conflict of interest, unless it is payment for legitimate research
      purposes, and the cash is not for purposes of marketing. (2) Marketing gifts,
      which benefit the patient, are acceptable as long as they are not of substantial
      value...like equal or less than $100. (3) Conferences (including a "mo dest"
      meal) sponsored by industry are acceptable when they serve a genuine educational
      function, and promote objective and scientific activity. (4) Professional people
      should understand and appreciate the marketing forces, which are endeavoring to
      influence our behavior. To interact with marketing people is appropriate, not
      unethical. However we must not be influenced in any way that would disadvantage
      our patients.

PMID- 17455582
TI  - History of DAKOTACARE, your company. Part 2 of a 2 part series.

PMID- 17455583
TI  - Medication therapy management: a Medicare Part D benefit available to qualifying
      beneficiaries.

PMID- 17455584
TI  - [Usefulness of statistics and epidemiological information on infectious diseases
      in the world and in Japan].

PMID- 17455585
TI  - [Emerging, re-emerging infectious diseases].

PMID- 17455586
TI  - [Infectious diseases in overseas travellers].

PMID- 17455587
TI  - [Zoonoses].

PMID- 17455588
TI  - [Species and properties of microorganisms used for bioterrorism].

PMID- 17455589
TI  - [Usefulness of infectious disease information on the internet].

PMID- 17455590
TI  - [Outline of the mechanism by which pathogenic microorganisms induce infectious
      diseases].

PMID- 17455591
TI  - [Pathogen recognition by Toll-like receptor].

PMID- 17455592
TI  - [Bacterial adherence of non-typable Haemophilus influenzae].

PMID- 17455593
TI  - [Invasion of pseudomonas aeruginosa into mammalian epithelial cells].

PMID- 17455594
TI  - [Surface receptors in relation to pathological differences between falciparum and
      vivax malaria].

PMID- 17455595
TI  - [Bacterial translocation].

PMID- 17455596
TI  - [NO-induced mutagenesis for microbial pathogen and host defense suppression].

PMID- 17455597
TI  - [Host defense system against infection].

PMID- 17455598
TI  - [Defence mechanisms against oral infections].

PMID- 17455599
TI  - [Host defense in respiratory infections].

PMID- 17455600
TI  - [Mucosal immune system: the second way of the host defense].

PMID- 17455601
TI  - [Roles of natural memory lymphocytes in host defense mechanisms].

PMID- 17455602
TI  - [Mechanisms of continuous and recurrent infection of lower respiratory tract].

PMID- 17455603
TI  - [Biofilm formation associated with persistent urinary tract infections].

PMID- 17455604
TI  - [Molecular mechanisms of persistent infection with mycobacterium tuberculosis and
      reactivation].

PMID- 17455605
TI  - [Recurrence of genital herpes simplex virus infection].

PMID- 17455607
TI  - [How to diagnose infectious diseases at the first visit of a patient--signs and
      symptoms which are suggestive of an infectious disease and appropriate timing of
      laboratory examination].

PMID- 17455606
TI  - [Human cytomegalovirus infection].

PMID- 17455608
TI  - [Appropriate interpretation of laboratory tests for infectious diseases].

PMID- 17455609
TI  - [Diagnosis of infectious diseases].

PMID- 17455610
TI  - [Significance and limitations of Gram' s stain].

PMID- 17455611
TI  - [Identification of bacteria].

PMID- 17455612
TI  - [Laboratory diagnoses for fungal infection].

PMID- 17455613
TI  - [Diagnostic methods for mycobacterial diseases].

PMID- 17455614
TI  - [Laboratory diagnostics of viral diseases].

PMID- 17455615
TI  - [Rapid diagnosis of infectious diseases].

PMID- 17455616
TI  - [Immunoassay for diagnosis of infectious diseases].

PMID- 17455617
TI  - [Molecular diagnostics of infectious diseases].

PMID- 17455618
TI  - [Imaging diagnosis of infectious diseases].

PMID- 17455619
TI  - [Neuroinfection].

PMID- 17455620
TI  - [Diagnosis of infective endocarditis by echocardiography].

PMID- 17455622
TI  - [Radiographic imaging of bacterial pneumonia].

PMID- 17455621
TI  - [Radiological analysis of pathogens which cause respiratory infections].

PMID- 17455623
TI  - [Imaging diagnosis of Legionella pneumophila pneumonia].

PMID- 17455624
TI  - [Imaging diagnosis of Mycoplasma pneumoniae pneumonia].

PMID- 17455625
TI  - [Image diagnosis of abdominal infectious diseases (infectious enterocolitis and
      Fitz-Hugh-Curtis Syndrome)].

PMID- 17455626
TI  - [Management of infectious diseases--principles and challenges].

PMID- 17455627
TI  - [Importance of appropriate carbapenem use to reduce carbapenem--resistant
      Pseudomonas aeruginosa].

PMID- 17455628
TI  - [Present condition of surgical infections].

PMID- 17455629
TI  - [Guidelines for the diagnosis and treatment of hemolytic uremic syndrome (HUS)
      with enterohemorrhagic colitis].

PMID- 17455630
TI  - [HIV/AIDS trends in Japan after publication of Japanese guidelines for treatment
      of patients infected with HIV].

PMID- 17455631
TI  - [The Japanese Respiratory Society guidelines for the management of community
      acquired pneumonia in adults--its spreading and results].

PMID- 17455632
TI  - [The Japanese Respiratory Society guidelines for management of hospital acquired
      pneumonia--its spreading and results].

PMID- 17455633
TI  - [Clinical guideline on upper respiratory tract infection in adults as proposed by
      Japanese Respiratory Society].

PMID- 17455634
TI  - [Guideline for the diagnosis and treatment of STDs--trends of diagnosis and
      treatment after publication].

PMID- 17455635
TI  - [Guideline for diagnosis and treatment of Helicobacter pylori infection].

PMID- 17455636
TI  - [Principles of treatment of infectious diseases with antimicrobial agents].

PMID- 17455637
TI  - [PK/PD of antimicrobials].

PMID- 17455638
TI  - [Positioning of steroids in the treatment of infectious diseases].

PMID- 17455639
TI  - [Immunoglobulin concentrate and G-CSF].

PMID- 17455640
TI  - [Switch therapy for community acquired pneumonia].

PMID- 17455641
TI  - [Antimicrobial cycling therapy].

PMID- 17455642
TI  - [beta-Lactam antibiotics].

PMID- 17455643
TI  - [Macrolides and ketolides].

PMID- 17455644
TI  - [Quinolone antibacterials--oral preparation].

PMID- 17455645
TI  - [Linezolid].

PMID- 17455646
TI  - [Streptogramins and glycopeptides].

PMID- 17455647
TI  - [Anti-tuberculosis drugs].

PMID- 17455648
TI  - [New antifungal drugs and strategies in antifungal chemotherapy].

PMID- 17455649
TI  - [Drugs for protozoan diseases].

PMID- 17455650
TI  - [Antiretrovirals].

PMID- 17455651
TI  - [Drugs for hepatitis B and C infection].

PMID- 17455652
TI  - [Antivirals for herpesviruses and cytomegalovirus].

PMID- 17455653
TI  - [Antiviral agents for influenza].

PMID- 17455654
TI  - [Roles of xenobiotic transporters in bacterial drug resistance and virulence].

PMID- 17455655
TI  - [Evolution and spread of SCCmec among staphylococci].

PMID- 17455656
TI  - [VRE, VRSA].

PMID- 17455657
TI  - [BIVR].

PMID- 17455658
TI  - [CA-MRSA].

PMID- 17455659
TI  - [Current status of PRSP and BLNAR].

PMID- 17455660
TI  - [ESBL and its producing organism].

PMID- 17455661
TI  - [Metallo-beta-lactamase producing bacteria].

PMID- 17455662
TI  - [Biochemical and genetical mechanisms in emergence of multidrug-resistant
      Pseudomonas aeruginosa (MDRP)].

PMID- 17455663
TI  - [Mechanism of drug resistance in M. tuberculosis and non-tuberculous acid-fast
      bacilli].

PMID- 17455664
TI  - [Mechanisms of resistance to antifungal agents].

PMID- 17455665
TI  - [Antiviral resistance of influenza viruses].

PMID- 17455666
TI  - [Mechanism of drug-resistance in human cytomegalovirus].

PMID- 17455667
TI  - [Antiviral resistance of herpes simplex virus and varicella-zoster virus].

PMID- 17455668
TI  - [Mechanisms of HIV drug resistance].

PMID- 17455669
TI  - [Mechanisms of drug resistance in hepatitis viruses B and C].

PMID- 17455670
TI  - [Protozoa (plasmodium) : mechanisms of resistance to antimalarials].

PMID- 17455671
TI  - [Prevalence and treatment for antibiotic-resistant bacteria in respiratory
      infection].

PMID- 17455672
TI  - [Current status and countermeasures for antibiotic resistant organisms in the
      field of surgery].

PMID- 17455673
TI  - [Actual situation in Japan of antimicrobial resistant isolates from patients with
      urinary tract infection and its control measures].

PMID- 17455674
TI  - [Current status of multi-drug resistant bacteria in infectious diarrheal diseases
      and its control].

PMID- 17455675
TI  - [Preventive measures for drug resistant bacteria by guidelines].

PMID- 17455676
TI  - [Management of antimicrobial resistance using information technology].

PMID- 17455677
TI  - [Antimicrobial stewardship for the prevention of antimicrobial resistance].

PMID- 17455678
TI  - [New quinolones].

PMID- 17455679
TI  - [Impact of so-called injectable third generation cephems].

PMID- 17455680
TI  - [Application of macrolides to diffuse panbronchiolitis].

PMID- 17455681
TI  - [Interferon therapy for hepatitis B and C].

PMID- 17455682
TI  - [Efficacy of clinical pathways in infectious diseases].

PMID- 17455683
TI  - [Usefulness of the antibiotics use manual in a hospital].

PMID- 17455684
TI  - [Randomized controlled trials of antibiotics for acute respiratory tract
      infections in adults].

PMID- 17455685
TI  - [Adverse effects and safety of antimicrobial agents--allergy].

PMID- 17455686
TI  - [Adverse effects and safety of antimicrobial agents-neurotoxicities].

PMID- 17455687
TI  - [Hematological side effects of antimicrobial agents].

PMID- 17455688
TI  - [Antimicrobial-drug induced hepatic injuries].

PMID- 17455689
TI  - [Adverse effects and safety of antimicrobial agents--nephrotoxicity].

PMID- 17455690
TI  - [Adverse effects and safety of antimicrobial agents--drug interactions].

PMID- 17455691
TI  - [Skin test for antibiotic anaphylaxis].

PMID- 17455692
TI  - [Adverse effects and safety of antimicrobial agents--necessity of intracutaneous
      reaction from the view point of medical legal].

PMID- 17455693
TI  - [Transplacentally acquired immunoglobulin G antibodies in newborns and infants].

PMID- 17455694
TI  - [Mucosal vaccine: the powerful weapon for the host defense].

PMID- 17455695
TI  - [Vaccines in Japan].

PMID- 17455696
TI  - [Travelers' vaccine].

PMID- 17455697
TI  - [Actual condition of Japanese infection prevention and control].

PMID- 17455698
TI  - [CDC guideline for infection control].

PMID- 17455699
TI  - [Healthcare-associated infection surveillance].

PMID- 17455700
TI  - [Management of occupational exposures to HBV, HCV, HIV, and TB].

PMID- 17455701
TI  - [Position of microorganisms in the natural world and their taxonomy and biosafety
      level].

PMID- 17455702
TI  - [Self-protection mechanisms of antibiotic-producing microorganisms].

PMID- 17455703
TI  - [Implication of viable but nonculturable (VNC) concept].

PMID- 17455704
TI  - [New findings on the biological activities of macrolides--antiviral effects of
      macrolide antibiotics].

PMID- 17455705
TI  - [Infection in orthopedics and traumatology: from basic research to future
      curative strategies].

PMID- 17455706
TI  - [Prevention of venous thromboembolism in orthopedic surgery and traumatology].

PMID- 17455707
TI  - Communication: patient safety and the nursing work environment.

PMID- 17455708
TI  - Nursing faculty speaks up!

PMID- 17455709
TI  - Impressions of nursing.

PMID- 17455710
TI  - Efficacy and safety of deep sclerectomy and phacoemulsification and deep
      sclerectomy in clinical material of Military Health Service Institute--yearly
      observations.
AB  - PURPOSE: Comparison of the effectiveness of nonpenetrated deep sclerectomy (DS)
      as the only procedure in relation to operation combined with phacoemulsification
      (FDS) in treatment of patients with open-angle glaucoma based on yearly
      observation. MATERIAL AND METHODS: 67 eyes with open-angle glaucoma were
      retrospectively analyzed. Applying layer-systematic criteria 21 eyes after deep
      sclerectomy with scleral implant (SKGEL/Corneal or T-flux/I-Tech) were selected
      into group I (DS implant) and 23 eyes after phacoemulsification with
      simultaneously performed deep sclerectomy and scleral implants were selected into
      group II (FDS implant). In control studies best corrected visual acuity (BCVA),
      intraocular pressure (IOP), anterior chamber and fundus, were examined.
      Postoperative complications and applied procedures were analyzed especially
      controlling hypotensive effect (goniopuncture, antimetabolites), as well as
      number of glaucoma medications used. Tests were performed in 1 and 7 days after
      surgery, and later after 1, 3, 6, 12 months. Statistically test U Mann-Whitney
      was used as well as pair sequence Wilcoxon test. Survival analysis was done with
      Kaplan-Meier method with the use of log rank test. RESULTS: After 360 days of
      observation mean values of IOP in group I was 14.3 +/- 3.6 mmHg, and in group II-
      12.9 +/- 3.0 mmHg. It was a decrease of mean IOP by 29.6% (p = .000) and 41.4% (p
      = .000) in comparison to preoperative IOP in particular groups. In both groups
      fewer glaucoma medications were used after surgery and the results were
      statistically significant (p < .05). As a complete success rate was considered
      IOP of < or =18 mmHg without glaucoma medications, and qualified success rate was
      IOP of < or =18 mmHg without medications or with the most of two glaucoma
      medications. Complete and qualified success rate were achieved respectively in
      group I (72.6% and 88.4%) and in group II (74.3% and 86.9%) at the end of
      observation. In the entire observation there were no statistically significant
      differences between group I and 2 (p > .05). After 360 days of observation there
      was no statistically significant difference between mean BCVA in group I and II
      (p > .05). CONCLUSIONS: DS with scleral implant performed as a single procedure
      or FDS is effective treatment in open-angle glaucoma.

PMID- 17455711
TI  - Comparison of surgically induced astigmatism of temporal versus superior clear
      corneal incisions.
AB  - PURPOSE: Comparison of the astigmatism induced by the operation based on the 2.8
      mm incisions in the clear cornea, performed by temporal approach and superior
      approach. MATERIAL AND METHODS: Retrospective analysis was performed on the group
      of 65 patients (41 women and 24 men), mean age 74.5 +/- 7.1 years old. We studied
      a series of 70 eyes (32 right eyes and 38 left eyes). All of the patients
      underwent cataract surgery by means of ultrasonic phacoemulsification conducted
      at the Department of Ophthalmology, Military Health Services Institute in Warsaw,
      Poland within 2004-2005. Follow-up examinations took place 6 months after
      operation. There were DBCVA. NBCVA, intraocular pressure, anterior segment of the
      eye and fundus examined. Curvature of the cornea was measured by means of Javal's
      ophthalmometry. The results were assumed as significant in view of corneal
      curvature stabilization. Vector analysis of astigmatism was performed on the
      basis of method described by Jaffe. There was preoperative astigmatism vector
      (K1) and post-operative astigmatism vector (K3) calculated, as well as surgically
      inducted astigmatism (SIA)--vector (K2). From the group of 70 eyes, 19 were
      excluded from the study, where vector K1 was > 1.0 D as well as four eyes, where
      the main opening site depended on the size and axis of K1 vector. The group of 47
      eyes was divided according to the opening site into two subgroups--group I
      (temporal approach--2.8 mm)--25 eyes and group II (superior approach 2.8 mm)--22
      eyes. Statistical analysis was performed based on Statistica package 6.0 PL.,
      using U-Mann-Whitney's test, Chi square Yates' test, Kruskal-Wailis' variance
      analysis, logistic regression and W Shapiro-Wilk's test. RESULTS: Studied groups
      were homogeneous with respect to age structure, sex, number of operated eyes and
      pre-operative size of corneal astigmatism vector K1 (p > .05). The mean values of
      SIA in group I and II were respectively: 0.63 +/- 0.28 and 1.00 +/- 0.54 and were
      statistically significant (p < .05). The mean values of K3 post-operative vector
      measured 6 months following the operation was: 0.54 +/- 0.35 in the group I and
      0.96 +/- 0.43 in the group II. Differences between two groups show statistical
      significance (p < .05). Size of SIA has crucial influence on generating post
      operative astigmatism > 1.0 D (p = .03). CONCLUSIONS: Clear corneal temporal
      approach 2.8 mm is more beneficial method comparing to superior approach of the
      same width, because of the scale of SIA.

PMID- 17455712
TI  - [Pseudoexfoliation syndrome in patients scheduled for cataract surgery].
AB  - PURPOSE: We present the results of a prospective investigation into the frequency
      of pseudoexfoliation syndrome (XFS), age, sex, intraocular pressure (IOP) and the
      type of lens opacity in patients scheduled for cataract surgery. MATERIAL AND
      METHODS: A series of 1000 consecutive patients (604 females and 396 males in the
      age from 26 to 97 years), who were admitted for cataract surgery to the
      Department of Ophthalmology of Medical University in Bialystok, were studied. All
      eyes were examined with a slit-lamp biomicroscope before and after mydriasis with
      1% tropicamide and 10% phenylephrine to find out the exfoliation. The type of
      cataract was classified as mainly nuclear, cortical, posterior subcapsular,
      mixed, mature or hypermature. Glaucoma was defined as IOP > or =21 mmHg with
      optic disc and/or visual field changes indicative of glaucoma. RESULTS:
      Exfoliation material was detected in 82 patients (8.2%). The mean age of patients
      with XFS (77.1 +/- 9.3 years) was significantly more than that of those without
      XFS (65.6 +/- 11.2 years), p < 0.01. The prevalence of XFS significantly
      increased with advancing age. Mature cataract and nuclear sclerosis predominated
      in eyes with XFS (32.9% and 24.4%, respectively) compared to those without XFS
      (24.6% and 14.2%), p < 0.05. Posterior subcapsular cataract was less common in
      eyes with exfoliation (9.7%) than in eyes without it (39.1%), p < 0.001. The mean
      preoperative intraocular pressure was higher in eyes with XFS (17.8 +/- 3.2
      mmHg), than in those without XFS (15.2 +/- 3.8 mmHg), p < 0.01. Glaucoma was
      found in 28 of 82 eyes with pseudoexfoliation syndrome (34.1%). CONCLUSIONS: The
      pseudoexfoliation syndrome occurred much more frequently in elderly persons. PEX
      has been found to be associated with higher mean intraocular pressure, glaucoma,
      mature and nuclear cataract. Posterior subcapsular cataract was less common in
      patients with PEX.

PMID- 17455713
TI  - [Influence of intraoperative complication on intraocular rigid lens fixation in
      pediatric cataract surgery].
AB  - PURPOSE: This paper presents the intraoperative complications in pediatric
      cataract surgery with IOL implantation and their influence on fixation place.
      MATERIAL AND METHODS: 384 eyes of 276 children undergone operative procedure for
      cataract. Anterior capsulorhexis, lens cortical aspiration, primary posterior
      capsulorhexis with anterior vitrectomy and IOL implantation were done in all
      eyes. The place of IOL implantation was capsular sac or ciliary sulcus. RESULTS:
      There were no serious intraoperative complications but in cases with large
      anterior (5.2%) and posterior (14.6%) radial capsule tears, vitreous loss
      (12.3%), and hemorrhage (5.5%) to anterior and posterior chamber the IOL was
      fixated at ciliary sulcus (in 37.5%). CONCLUSIONS: The surgical procedure is
      useful and safe in the management of pediatric cataract. Location of an IOL in
      the ciliary sulcus in a child, is acceptable. To avoid decentration in this
      cases, we recommend rigid PMMA IOLs.

PMID- 17455714
TI  - [Nonoperative treatment of diplopia after IOL implantation].
AB  - PURPOSE: Analysis of effects of non-operative treatment of diplopia complicating
      cataract surgery with IOL implantation or secondary IOL implantation. MATERIAL
      AND METHODS: 22 patients with diplopia occurring after cataract surgery with IOL
      implantation or secondary IOL implantation were enrolled into the study. Only the
      patients who were not eligible for surgery or declined surgical treatment, were
      included. Each patient had complete ophthalmic and orthoptic examination with
      Hess-screen-test and prism alternate cover tests. Predicting factors of
      persistent diplopia were determined. RESULTS: The therapy consisted of prism
      correction in 77.3% of patients and prism with botulin toxin injections in 9.1%
      of patients. In two persons diplopia persisted due to cyclotrophia and
      decentration of IOL, and these patients were eventually treated surgically. The
      treatment was succesful in 72.7% of patients in whom single vision was achieved.
      In 18.2% of patients occasional diplopia was found and in 9.1% the therapy was
      not effective. Disorders precipitated by prolonged cataract--related occlusion
      and uncorrected aphakia, disorders resulting from surgical trauma to extraocular
      muscles (retrobulbar or peribulbar anesthesia) and preexisting complications of
      ocular alignment, all predict related persistent diplopia after IOL implantation.
      CONCLUSIONS: (1) Cataract surgery with IOL and secondary IOL implantation should
      be performed before the loss of binocular function. (2) Retrobulbar and
      peribulbar anesthesia may cause surgical muscular trauma, therefore topical
      anesthesia is recomended. (3) Prism correction (with or without botulin toxin
      injection) is an effective therapy.

PMID- 17455715
TI  - [The results of panphotocoagulation laser treatment in retinopathy of prematurity
      in the West Pomeranian Region in 2003-2005 years].
AB  - PURPOSE: ROP--retinopathy of prematurity is a disease of the retina and the
      vitreous body of premature infants, especially born before 28 weeks of
      intrauterine life (71%), rare till 33 weeks of pregnancy (7.6%). The pathogenesis
      is involved with damage of immature vessels of the retina. The disease seems to
      self-regress in 80%. According to stage of changes of the retina there could be
      some complications of the organ of vision like: refractive errors, disturbances
      of eyeball movement, poor vision or even blindness (19.01%). ROP is now second
      (after atrophy of the optic nerve) cause of blindness in children (3). Aim of our
      study was the analysis of the results of laser-treatment in ROP in West
      Pomeranian region in years 2003-2005 and estimation of the risk factors of
      advanced stages of ROP. MATERIAL AND METHODS: Since January 2003 to June 2005 in
      Outpatients Clinic for Premature Infants of the Ophthalmology Department of The
      West Pomeranian Medical University in Szczecin we have examined 708 children. 40
      premature infants (78 eyes) were treated with panphotocoagulation of the retina
      because of advanced ROP We have used the Ocu-Lights SL laser, manufactured by
      Iris Medical. RESULTS: Laser treatment caused regression of ROP in 88.5% of
      children. In 11.5% the progression of ROP caused secondary retina detachment.
      CONCLUSIONS: Respiratory failure, anemia, infections and multi-organ
      inflammations increase the risk of ROP Good results of laser treatment depend of
      beginning of the therapy in the right stage of ROP On the final results of
      treatment could have got the influence both: immaturity of the child and the
      showed risk of factors.

PMID- 17455716
TI  - [The estimation of selected parameters in antioxidant system in red blood cells
      in ROP screening of premature infants].
AB  - PURPOSE: To estimate correlation between concentration of antioxidant system
      parameters in red blood cells in premature infants and prevalence of ROP MATERIAL
      AND METHODS: We examined 16 premature infants with the average birth weight of
      1071 g and gestational age of 29.1 weeks. Supraoxide dismutase (SOD), reduced
      glutatione (GSH), and glutathione peroxidase (GSH-Px), were measured at day 1
      (cord blood), 7-th and 14-th day after birth. Premature infants had ROP
      screening. The control group included 12 infants born at term. RESULTS: 8
      premature infants had ROP There were higher levels of SOD, GSH and GSH-Px in
      premature infants with and without ROP than in control group. Premature infants
      with ROP had lowest levels of GSH. CONCLUSIONS: The glutathione status of red
      blood cells as a oxidative stress index in premature infants might be a reliable
      parameter, facilitating the early recognition of patients in immediate danger of
      ROP development.

PMID- 17455717
TI  - [Assessment of the ocular changes in children with juvenile idiopathic
      arthritis].
AB  - PURPOSE: To analyse the frequency of uveitis and other ocular changes in children
      with juvenile idiopathic arthritis. MATERIAL AND METHODS: We carried out
      ophthalmologic examination in children and adolescents with juvenile idiopathic
      arthritis, in age between 3 and 20 years. During the examination we evaluated
      vision acuity, refraction, anterior and posterior part of the eye and intraocular
      pressure. RESULTS: A total of 48 (68%) girls and 22 (32%) boys participated in
      our study, whose mean age was 13.2 years (SD = 3.8). The most frequent onset of
      juvenile idiopathic arthritis was oligoarticular form of the disease (62%). Only
      in 42% of the studied group there were no significant abnormalities of the ocular
      system. Anterior uveitis was diagnosed in 5 patients (7%) including 4 (5.7%)
      girls and 1 (1.4%) boy. Complications appeared in 2 children in the form of
      cataract and band keratopathy which both resulted in considerable impairment of
      visual acuity. Mean duration of juvenile idiopathic arthritis before the onset of
      uveitis was 5.2 years. There were other ocular changes in the studied group,
      among which the most common were: conjunctivitis--24%, abnormalities of the
      retina--11%, glaucoma--4% and other changes. CONCLUSIONS: In majority of the
      children with juvenile chronic arthritis different abnormalities of the eyes were
      diagnosed. All the patients with juvenile idiopathic arthritis should be under
      close surveillance of the ophthalmologist, irrespective of the disease duration.

PMID- 17455718
TI  - [Impression cytology in patients with dry eye syndrome and various rheumatic
      diseases].
AB  - PURPOSE: The aim of this study was to evaluate the cytological changes of bulbar
      conjunctiva in patients with various rheumatic diseases and dry eye syndrome.
      MATERIAL AND METHODS: 60 patients with rheumatoid arthritis (RA), systemic
      scleroderma (SScl), primary Sjbgren syndrome (pSS), systemic lupus erythematosus
      (SLE) and dry eye syndrome were studied. The ocular examination consisted of
      Schirmer I, break- up time of tear film (BUT), fluorescein and lissamine green
      staining and impression cytology of bulbar conjunctiva. RESULTS AND CONCLUSIONS:
      The morphological alternations of bulbar conjunctiva seen in impression cytology
      specimens correlated with clinical signs of dry eye syndrome.

PMID- 17455719
TI  - [Multifocal oscillatory potentials (mfOPs) in patients with central retinal vein
      occlusion].
AB  - PURPOSE: To evaluate usefulness of multifocal oscillatory potentials (mfOPs) in
      diagnostics in patients with retinal vein occlusions. MATERIAL AND METHODS: The
      Visual Evoked Imaging System (VERIS, version 4.9) was used to stimulate the
      visual system to elicit mfOPs from 103 areas subtending the central 70-80 degrees
      of the retina in three patients with central or branch retinal vein occlusions.
      Two stimulating conditions were used. For each subject, the mean first- and
      second-order kernel responses from occlusion area, were analyzed and compared
      with the fellow eye and control subjects results. RESULTS: In retinal areas
      without circulatory disturbances in fluorescein angiography all mfOPs components
      were present. In a patient with branch retinal vein occlusion in the area without
      capillary perfusion mfOPs responses were not detectable. CONCLUSIONS: The mfOPs
      are in a large extent dependent on a proper retinal circulation. The recording of
      mfOPs may be useful in clinical diagnosis, to asses circulatory disturbances in
      internal layers of the retina and in differentiation of ischemic from non
      ischemic retinal vein occlusions.

PMID- 17455720
TI  - [Treatment of entropion using mucous membrane and cartilage grafts from the nasal
      septum].
AB  - The aim of the study was to assess the outcome of treatment of entropion by means
      of mucous and cartilage grafts, harvested from the nasal septum. From 1989 to
      2004 thirteen patients with entropion resulting from chemical and thermal burning
      or mechanical trauma were treated at the Hospital of Plastic Surgery in Polanica
      Zdr6j. Upper eyelid deformities were corrected in 14 cases, while the lower
      eyelid was repaired in 3 cases. Blepharotomy was performed by means of subciliary
      incision. Compound mucous and cartilage grafts harvested from the nasal septum,
      were sutured into the defects. Very good results and complete resolution of
      contractures were obtained in 15 cases, while 2 patients underwent a repeated
      surgery in which compound grafts were used again. According to the author's
      opinion, the above described method is an effective modality of treatment of
      cicatricial entropion.

PMID- 17455721
TI  - Report of a case of malignant melanoma of the limbus (30-thy years of
      observation).
AB  - PURPOSE: To describe a case of a malignant melanoma of the limbus. MATERIAL AND
      METHODS: A 49-year-old female patient with a suspected malignant limbic melanoma
      in the left eye. The first signs appeared in 1975, manifested as reddening of the
      left eye on the temporal side with markedly dilated conjunctival vessels. In
      1993, the lesion became pigmented and nine years later its progression was noted.
      In May 2003, lamellar keratoplasty of the left eye was performed under general
      anaesthesia. RESULTS: Histologic assessment--spindle cell malignant melanoma. The
      entire tumour was resected and the cosmetic result was very good. The results of
      accessory diagnostic studies were within normal limits. Over a 28-month follow-up
      period no local recurrence or metastases to other sites were observed.
      CONCLUSION: Patients with discoloration of the conjunctivae should be regularly
      evaluated by an ophthalmologist and an oncologist.

PMID- 17455722
TI  - [The Klippel-Trenaunay-Parkes-Weber syndrome as an example of genetic disorder of
      angiogenesis].
AB  - PURPOSE: To report on the congenital vascular malformation snyndrome Klippel
      Trenaunary-Parkes-Weber (KTPW), which has recently been the focus of research on
      angiogenesis. MATERIAL AND METHODS: A case report which includes a fluorescein
      angiography, cerebral MRI, the investigation of parameters for congenital
      disorders of blood coagulation, structural and numerical analyses of chromosomes.
      RESULTS: All three typical symptoms of KTPW were found. An old cerebral insult in
      the thalamus with vascular encephalopathy was established with MRI. The direction
      of the venous drainage in the fusiform arterial-venous malformation of
      conjunctiva in the right eye has been changed during the observation. Dilated
      retinal veins were observed in the fluorescein angiography of the right eye.
      Structural changes in karyograms were also seen. CONCLUSIONS: The congenital
      arterial-venous malformation in conjunctiva has been changed through venous
      thrombosis during our long observation. Anticoagulation therapy or surgical
      therapy of pathologic veins in childhood, should be recommended.

PMID- 17455723
TI  - [Cataract in an atopic dermatitis patient--case report and review of the
      literature].
AB  - Atopic cataract is one of several kinds of presenile cataracts, which develops in
      20% of patients suffering from atopic dermatitis. Atopic cataract is the most
      frequently bilateral and characterized by fast progression. This type of cataract
      creates more and more important social problem, because of the young age of
      patients, who are usually professionally active and increasing incidence of
      atopic dermatitis in population. The aim of this paper is to present the case
      report of the atopic cataract in patient who was operated in the Regional
      Ophthalmologic Hospital in Krakow, and the review of the literature.

PMID- 17455724
TI  - [The detachment of retina as possible complication after BCG vaccination during
      HOP--description of case].
AB  - PURPOSE: The authors described the rare case of the progression of changes in the
      retina of child in course of retinopathy of prematurity. It happened after
      finished laser-treatment and full regression of changes of the retina. It seems
      that BCG vaccination done in 3-th month of life could reactivate the disease of
      the retina which caused total retina detachment of both eyes. MATERIAL AND
      METHODS: The ophthalmologic examination included: indirect ophthalmoscopy using
      Fisson ophthalmoscope, slit-lamp examination and USG B-mode examination, using
      USG Echo Scan 3300 Oculus with the head 10 MHz--performed during all control
      visits. RESULTS: The regular ophthalmologic examination enabled estimation of the
      dynamic of changes in the retina and correctness of treatment. In author's
      opinion, the secondary retina detachment in 3-th month of life could be
      associated with reaction post BCG vaccination. CONCLUSIONS: Probably secondary
      inflammation after BCG vaccination could be the reason of reactivation of earlier
      treated with good results ROP Possible vision complications should incline to
      take special ophthalmologic care of premature infants from high risk group (very
      low mass of the body or fetal immaturity). Decision of changing time of BCG
      vaccination in such group should be made by attending physician.

PMID- 17455725
TI  - [Bilateral Adie's syndrome in child].
AB  - Bilateral Adie's syndrome is characterized by the presence of a tonic pupil
      connected with accommodation problems. Very often, it coexists with latent
      hypermetropia, corneal hyposensivity. Typical signs are weakened tendons
      reflexes. We present the 8 years old girl with bilateral Adie's syndrome, which
      was the cause of school problems.

PMID- 17455726
TI  - [Application of retinal thickness analyzer (RTA) in diagnosis and treatment
      monitoring in retinal diseases].
AB  - The aim of the study was to evaluate the applicability of retinal thickness
      measurements using the Retinal thickness analyzer (RTA) in diagnosis and
      monitoring treatment of a variety of eye diseases. MATERIAL AND METHODS: Patients
      with various retinal diseases (diabetic macular edema, branch retinal vein
      occlusion, age-related macular degeneration, and primary open-angle glaucoma),
      were examined for retinal thickness in the posterior pole using the Retinal
      thickness analyzer. A laser light beam of a 543 nm wave length was projected on
      the retina and scanned across 3x3 mm retinal area. Five scans covered the 200
      area of the fundus. The images of the particular intersections were digitally
      recorded and the results were presented as colour maps and diagrams. RESULTS: The
      examination carried out with Retinal thickness analyzer showed the retinal
      thickening in patients with diabetic macular edema and branch retinal vein
      occlusion. Leakage from subfoveal choroidal neovascular membranes resulted also
      in retinal edema and thickening. Fluorescein and indocyanine green angiography
      confirmed the diagnosis. Evaluation of the retinal nerve fibre layer in patient
      with primary open angle glaucoma, confirmed a thinning of the retina in the
      region of posterior pole. CONCLUSIONS: The scanning Retinal thickness analyzer
      provides an essential information useful in diagnosis and monitoring treatment of
      retina diseases in the macula region.

PMID- 17455727
TI  - [Traction maculopathies--pathogenesis and diagnostics].
AB  - Traction maculopathies are a group of age-related degenerative diseases
      characterized by pathology of vitreomacular interface including idiopathic
      epimacular membranes, vitreomacular traction syndrome and idiopathic macular
      hole. The disorders develop due to mechanical forces caused by focal condensation
      or incomplete detachement of vitreous and shrinkage of pathological membranes.
      The forces can be tangential to retinal surface in epiretinal membranes, anterior
      posterior in vitreomacular traction syndrome and oblique (trampoline) in
      idiopathic macular hole. Authors discuss pathogenesis and diagnostics of traction
      maculopathies with use of optical coherence tomography and microperimetry, based
      on current literature. This work presents also idiopathic macular hole
      classification with use of optical coherence tomography images compared with
      biomicroscopic classification by Gass.

PMID- 17455728
TI  - [Internal limiting membrane removal. Mechanical and fluid membranectomy].
AB  - The purpose of this study is presentation of some surgical methods used during
      the removal of internal limiting membrane of retina, or its complex with
      epiretinal membrane. At the beginning, the procedure was reserved only for
      difficult cases so in such conditions we can hardly expect very good results.
      Removing of epiretinal membranes became more common of late twenty years and
      macular surgery began to comprise greater percentage of vitreoretinal surgeries.
      Indications for the type of this procedure were significantly enhanced, as well.

PMID- 17455729
TI  - [25 gauge technology in vitrectomy: pro and con].
AB  - In the article authors present new technology of performing vitrectomy. During
      the surgery w e used tools twice lesser in diameter than in traditional method.
      Main indications for its use are: macular hole (stage II, III and IV), idiopatic
      epiretinal membrane (cellophane maculopathy, macular pucker), secondary
      epiretinal membrane, vitreotraction macular syndrome, endophthalmitis,
      haemophthalmia, traction retinal detachment, diabetic macular edema,
      proliferative diabetic retinopathy, giant retinal tears, radial optic neurotomy,
      sheathotomy. At present, the best alternative is one day surgery. witrektomia 25
      gauge, chirurgia szklistkowo-siatk6wkowa, bezszwowa witrektomia. 25 gauge
      vitrectomy, vitreoretinal surgery, sutureless vitrectomy.

PMID- 17455730
TI  - [Stem cells--new perspectives in the treatment of retinal disorders].
AB  - The progress of clinical science since a few last years indicates the possibility
      that stem cells could be used in the treatment of retinal disorders. The bone
      marrow seems to be the most available source of the stem cells for such purposes.
      This review describes the latest attempts to use the stem cells, isolated from
      the bone marrow, in the treatment of retinal injuries. The research performed in
      animal models, so far gives hope to use that innovatory strategy in humans.

PMID- 17455731
TI  - [The Madrid classification of dry eye syndrome--own comments].
AB  - The dry eye syndrome is nowadays known as one of the most frequent reasons of
      long lasting discomfort and irritation of the eyes. From the clinical point of
      view, there are many etiologic causes, several combinations of anatomy pathologic
      manifestation and different grades of severity of dry eye diseases in the
      dysfunctional tear film syndrome. The ophthalmologist must recognize this three
      parameters, quantify them, and establish the most appropriate treatment. So, for
      this reason, in the 14th Congress of the Societas Ophthalmologica Europaea
      (Madrid, 2003), a multicenter study developed a practical classification of
      patients with ocular surface dryness based on etiology, histopathology and
      clinical severity of symptoms.

PMID- 17455732
TI  - [Topical prostaglandins influence over cornea--preliminary report].
AB  - In the article the recent research on the biology of corneal stroma and
      biological impact of topical prostaglandin analogues on this tissue, were
      presented. The outcome of some studies, regarding influence of this class of
      antiglaucoma medication on central corneal thickness (CCT), were included. The
      impact of CCT on the readings of intraocular pressure and the aspect of diurnal
      fluctuations of CCT were also emphasized.

PMID- 17455733
TI  - [Pegaptanib sodium in treatment of wet AMD].
AB  - Taking into consideration that the advanced stage of Age related Macular
      Degeneration is a very common cause of social blindness and present results of
      laser photocoagulation, PDT treatment and TTT are not satisfying, it seems to be
      of huge importance to look for new types of treatment, to improve visual
      outcomes. Repeated intravitreal injection of pegaptanib sodium (a VEGF aptamer)
      is a modern procedure which may not only give stabilization of visual acuity, but
      it may also lead to the improvement in high percentage. In this paper there is a
      short update on the epidemiology and the symptoms of the disease and the role of
      VEGF and its isoforms expression in the development of wet AMD. The presentation
      of pegaptanib sodium (Macugen) focus on its mechanism of action. Finally
      V.I.S.I.O.N. trial results are presented to show encouraging efficacy of the
      procedure.

PMID- 17455734
TI  - [Did Leon Wyczokowski suffer from solar maculopathy?].
AB  - Noted Polish painter, Leon Wyczolkowski, during his long-standing in Ukraine used
      to paint pictures gazing directly at the sun in order to intensify visual
      sensations. Damage to the eyes caused by sunlight induced him to become a patient
      of a famous ophthalmologist in Kiev. Past disease led to blue color vision
      impairment just like it happens to people who previously suffered from solar
      maculopathy. We suppose, it could gradually force the artist to resign from color
      painting and to take up drawing.

PMID- 17455735
TI  - [Post-lumbar puncture headache].
AB  - The postdural puncture headache is a frequent iatrogenic complication due to an
      excessive leakage of cerebrospinal fluid. The leak through the dural perforation
      mainly depends on the size and design of the needle. The diagnostic is based on
      the notion of dural puncture, headache worsening in upright posture and other
      symptoms as neck stiffness, tinnitus, hypacusia, photophobia or nausea. Symptoms
      resolve spontaneously within 1 week or within 48 hours after autologous epidural
      blood patch. Prevention is based on using small-gauge pencil-point needles
      whereas the duration of bed rest has no effect on the incidence of postlumbar
      puncture headache.

PMID- 17455736
TI  - [Digital necrosis in scleroderma].

PMID- 17455737
TI  - [Testicular cancer. Standard management leads to recovery in 90 to 95 percent of
      the cases].

PMID- 17455738
TI  - [Diagnosis and staging of germ-cell tumours of the testis].
AB  - The diagnosis of germ-cell tumour is based on the histological examination of the
      inguinal orchiectomy specimen. The histological classification allows
      discriminating seminoma and non seminomatous tumours. Non seminomatous tumours
      are heterogeneous, different sub-groups are described: embryonal carcinoma,
      teratoma, choriocarcinoma, yolk sac tumours, but components are often mixed.
      Serum tumour markers, human chorionic gonadotropin hormone and alpha
      foetoprotein, are important as well in the initial diagnosis, the prognosis, and
      follow-up of the disease. The staging procedure is strict and the prognostic
      factors allow defining the optimal treatment according to well established
      guidelines. Complete information of the patient is mandatory. All consequences of
      the disease and treatment must be managed, the most important being sperm
      conservation.

PMID- 17455739
TI  - [Management of localized germ-cell tumours of the testis].
AB  - Stage 1 is currently the most frequent pattern at diagnosis of germ-cell tumours.
      Prognosis is excellent and different options are available after orchidectomy.
      The therapeutic choice should be taken after fair and extensive information
      regarding the limitations of each option therefore taking into account both
      predictive factors of relapse and patient individual willing. In case of pure
      seminoma, prophylactic radiotherapy directed to the retroperitoneal lymph nodes,
      chemotherapy by single-agent carboplatin and surveillance with differed treatment
      at relapse are the three currently available attitudes. In non-seminomatous germ
      cell tumours three options should also be considered: surveillance (watchful
      waiting), chemotherapy by two cycles of BEP, or retroperitoneal lymph node
      dissection.

PMID- 17455740
TI  - [Chemotherapy for metastatic germ cell tumours of the testis].
AB  - The gold standard regimen for metastatic testicular germ cell tumours is a
      combination of bleomycin, etoposide and cisplatin. The number of cycles is
      defined by pathology (seminoma or non seminoma) and the prognostic criteria of
      the international classification (degree of elevation of serum tumour markers and
      presence or not of non pulmonary visceral metastases). The surgical resection of
      all residual metastatic masses is mandatory after the normalization of serum
      tumour markers in non seminoma patients. The cure rates after chemotherapy and
      surgery are about 90% and 50% in good-risk and poor-risk patients, respectively.

PMID- 17455741
TI  - [Surgery of residual masses after chemotherapy in patients with testicular
      cancer].
AB  - Advanced non seminomatous germ cell tumours are rare diseases affecting young
      men. Advanced disease is curable in 80% of the cases. The primary site of
      metastases is the retroperitoneal lymph nodes. Secondary metastatic sites are the
      lungs and mediastinal lymph nodes. Cisplatin-based chemotherapy has dramatically
      improved the prognosis of germ cell tumours, but surgery, when applicable,
      remains a central part of treatment. Forty five per cent and 10% of residual
      masses contain teratoma or active disease respectively. Residual masses of pure
      seminoma are removed only when postoperative pet-scan evaluation is positive or
      when they have grown during the follow-up period. All surgical procedures must be
      performed in a reference center.

PMID- 17455742
TI  - [Patient's medical record: auto-sperm preservation].

PMID- 17455743
TI  - [Open letter to academic medicine].

PMID- 17455744
TI  - [Lesions of ligaments and menisci of the knee and the ankle].

PMID- 17455745
TI  - [Medical certificates. Death and legislation. Organ procurement and legislation].

PMID- 17455747
TI  - [Evaluation of the severity and monitoring of early complications in
      multitrauma].

PMID- 17455746
TI  - [Treatment of cancer: surgery, radiotherapy, chemotherapy, hormonal therapy.
      Multidisciplinary therapeutic decision making and informing the patient].

PMID- 17455748
TI  - [The saga of the Flexner brothers].

PMID- 17455749
TI  - Set-size effects in simple visual search for contour curvature.
AB  - In a visual-search paradigm, both perception and decision processes contribute to
      the set-size effects. Using yes - no search tasks in set sizes from 2 to 8 for
      contour curvature, we examined whether the set-size effects are predicted by
      either the limited-capacity model or the decision-noise model. There are
      limitations in perception and decision-making in the limited-capacity model, but
      only in decision-making in the decision-noise model. The results of four
      experiments showed that the slopes of the logarithm of threshold plotted against
      the logarithm of set size ranged from 0.24 to 0.32, when the curvature was high
      or low, contour convexity was upward or downward, and stimulus was masked or
      unmasked. These slopes were closer to the prediction of 0.23 by the decision
      noise model than that of 0.73 by the limited-capacity model. We interpret this
      that in simple visual search for contour curvature, the decision noise mainly
      affects the set-size effects and perceptual capacity is not limited.

PMID- 17455750
TI  - Attention and spatial resolution: a theoretical and experimental study of visual
      search in hierarchical patterns.
AB  - Our aim has been to study visual search in hierarchical patterns through a
      computational neuroscience perspective. In this way we were able to analyse the
      relationship between the global precedence effect and attention. The theoretical
      part of our investigations extended a model built upon the biased-competition
      hypothesis. An important feature of this extension is that different spatial
      frequencies are processed with different time constants. Simulations with this
      model resulted in specific predictions that were confirmed with a novel visual
      search experiment utilising hierarchical patterns. Both experiment and
      simulations suggest that the global-precedence effect prevails under the
      condition of visual search.

PMID- 17455751
TI  - Size matters: saccades during scene perception.
AB  - We investigated the effect of image size on saccade amplitudes. First, in a meta
      analysis, relevant results from previous scene perception studies are summarised,
      suggesting the possibility of a linear relationship between mean saccade
      amplitude and image size. Forty-eight observers viewed 96 colour scene images
      scaled to four different sizes, while their eye movements were recorded. Mean and
      median saccade amplitudes were found to be directly proportional to image size,
      while the mode of the distribution lay in the range of very short saccades.
      However, saccade amplitudes expressed as percentages of image size were not
      constant over the different image sizes; on smaller stimulus images, the relative
      saccades were found to be larger, and vice versa. In sum, and as far as mean and
      median saccade amplitudes are concerned, the size of stimulus images is the
      dominant factor. Other factors, such as image properties, viewing task, or
      measurement equipment, are only of subordinate importance. Thus, the role of
      stimulus size has to be reconsidered, in theoretical as well as methodological
      terms.

PMID- 17455752
TI  - Changing viewpoints during dynamic events.
AB  - The connection of various viewpoints of a visual dynamic scene can be realised in
      different ways. We examined if various presentation modes influence scene
      recognition and cognitive representation type. In the learning phase,
      participants saw clips of basketball scenes from (a) a single, unvaried
      viewpoint, or with a change of viewpoint during the scene, whereby the connection
      was realised (b) by an abrupt cut, or (c) by a continuous camera move. In the
      test phase, participants had to recognise video stills presenting basketball
      scenes from the same or differing viewpoints. As expected, cuts led to lower
      recognition accuracy than a fixed unvaried viewpoint, whereas this was not the
      case for moves. However, the kind of connection between two viewpoints had no
      influence on the viewpoint dependence of the cognitive representation.
      Additionally, it was found that the amount of viewpoint deviation seemed to
      influence the overall conservativeness of participants' reactions.

PMID- 17455753
TI  - Does an estimate of environmental size precede size scaling on a form-comparison
      task?
AB  - In a number of studies reaction time has been found to increase with increases in
      size ratio on a same -different form-comparison task. Bennett and Warren (2002,
      Perception & Psychophysics 64 462-477) teased apart environmental and retinal
      size ratios by showing the forms along a (simulated) texture hallway, viewed
      monocularly, on a simultaneous form-comparison task; roughly equal effects of
      environmental and retinal size ratios were found. The current study enhanced
      scene-size information by showing the forms in simulated stereo and by adding
      texture to the forms themselves; special care was also taken to perceptually
      isolate the stimuli. In two experiments, with different kinds of forms, strong
      effects of environmental size ratio were found; no effect of retinal size ratio
      (same trials) was observed in either experiment. The results support the
      hypothesis that the (same-trial) form-size codings reflect 'all told' estimates
      of environmental size, and place constraints on modeling the functional
      architecture of the visual system.

PMID- 17455754
TI  - Control of the corridor illusion in baboons (Papio papio) by gradient and linear
      perspective depth cues.
AB  - The corridor illusion was recently demonstrated in baboons with background
      pictures containing rich depth information (Barbet and Fagot 2002, Behavioural
      Brain Research 132 111-115). In the current research we determined the
      contribution of gradient texture and perspective lines to that illusion. In
      experiment 1, the corridor illusion was tested in two baboons, with pictures of a
      hallway as backgrounds, or the same image of the hallway represented by
      perspective lines. Findings confirmed that the baboons experience the corridor
      illusion with the picture of the hallway, and showed that this illusion remained
      with the perspective-line backgrounds. The same procedure was adopted in
      experiment 2, but with a hallway drawn from gradient textures. The two baboons
      experienced the illusion in this experiment too. Thus both gradient and
      perspective line cues convey sufficient information to control the corridor
      illusion in baboons. In baboons, the processing of these two kinds of depth cues
      interacts with the perception of object size, suggesting homologous processes of
      pictorial depth perception in humans and non-human primates.

PMID- 17455755
TI  - Smooth-shape assumption for perceiving shapes from shading.
AB  - Humans can perceive three-dimensional shapes from shading, but reconstructing the
      original shape of an object from shading alone (luminance distribution) is
      mathematically impossible. Researchers have used different assumptions and
      reported that the human visual systems can resolve this difficulty. Here, we
      propose an assumption for perceiving shape from shading: that the object shape is
      assumed to be smooth rather than angular. In experiment 1, we investigated the
      effect of shape smoothness by manipulating the shading profile of the test
      region. In experiment 2, we further investigated the effect of shape smoothness
      by manipulating shapes of the regions bordering on the test region using
      binocular disparity. Each stimulus in our experiments is interpretable from
      shading as having either smooth or angular edges. Observers responded to the
      perceived shape while viewing the stimuli, and most tended to perceive smooth
      rather than angular edges. These results support the idea that the smooth-shape
      assumption is effective for perceiving shape from shading.

PMID- 17455756
TI  - Learning to perceive with a visuo-auditory substitution system: localisation and
      object recognition with 'the vOICe'.
AB  - We investigated to what extent participants can acquire the mastery of an
      auditory-substitution-of-vision device ('The vOICe') using dynamic tasks in a
      three-dimensional environment. After extensive training, participants took part
      in four experiments. In the first experiment we explored locomotion and
      localisation abilities. Participants, blindfolded and equipped with the device,
      had to localise a target by moving a hand-held camera, walk towards the target,
      and point at it. In the second experiment, we studied the localisation ability in
      a constrained pointing task. In the third experiment we explored participants'
      ability to recognise natural objects via their auditory rendering. In the fourth
      experiment we tested the ability of participants to discriminate objects
      belonging to the same category. We analysed participants' performance from both
      an objective and a subjective point of view. The results showed that
      participants, through sensorimotor interactions with the perceptual scene while
      using the hand-held camera, were able to make use of the auditory stimulation to
      obtain the information necessary for locomotor guidance, localisation, and
      pointing, as well as for object recognition. Furthermore, analysis from a
      subjective perspective yielded insights into participants' qualitative experience
      and into the strategies they used to master the device, and thus to pass from a
      kind of deductive reasoning to a form of immediate apprehension of what is being
      perceived.

PMID- 17455757
TI  - How to keep a reversible figure from reversing: teasing out top-down and bottom
      up processes.
AB  - The nature of processes underlying our perception of reversible figures was
      examined through two experiments investigating the effects of prior exposure
      conditions on an observer's report of figural reversal. In experiment 1,
      observers were adapted over several minutes to an unambiguous version of a
      rotating Necker cube prior to the presentation of the standard ambiguous figure.
      Results indicated that adaptation produced an immediate bias to perceive the
      ambiguous figure in the opposite configuration (ie reverse bias) and to reduce
      reports of reversal over the test period. The introduction of a brief delay
      between the adaptation and test periods revealed that this bias is a highly
      transient effect and is only clearly evident when the adaptation and test figures
      are matched in size. In experiment 2, observers were primed with an unambiguous
      figure for a few seconds prior to the presentation of the standard ambiguous
      figure. In this case, the obtained bias strongly favored the observer's reporting
      the ambiguous figure to be in the same configuration as the adapting figure (ie
      positive bias); and neither introducing a delay period nor changing figure size
      had any effect. We conclude that these experiments reveal the distinct roles of
      transient, retinally localized neural processes as well as more stable, global
      processes under specifiable conditions.

PMID- 17455758
TI  - The effect of rotation on configural encoding in a face-matching task.
AB  - Inversion disrupts encoding of faces because of the disruption of configural
      encoding as evident in the Thatcher illusion (Thompson 1980, Perception 9 483
      484). Here we consider the effect of rotation on the loss of configural encoding
      in a same/different matching paradigm. Participants decided whether two faces
      were of the same type (both normal or both Thatcherised) or not, at five angles
      of rotation (0 degrees, 45 degrees , 90 degrees, 135 degrees, 180 degrees). When
      the faces were both of the same person, the disruption due to rotation for 'same
      type' judgments was linear and approximately equal for normal and Thatcherised
      face pairs. In experiment 2, with different-person face pairs, the effect of
      rotation was much greater for Thatcherised face pairs than for normal face pairs.
      These findings are in contrast to those reported by Boutsen and Humphreys (2003,
      Quarterly Journal of Experimental Psychology A 56 955-975), and reasons for these
      differences, along with implications, are discussed.

PMID- 17455759
TI  - Eye vergence is susceptible to the hollow-face illusion.
AB  - When an observer looks at a hollow mask of a face, a normal convex face is often
      perceived [the hollow-face illusion--Gregory 1973, in Illusion in Nature and Art
      (London: Duckworth) pp 49-96]. We show that in exploring an illusory face, the
      eyes converge at the illusory and not at the real distances of fixated targets
      like the tip of the nose. The 'vergence error' appears even though the resulting
      disparities of the two retinal images of the target provide feedback that would
      allow an immediate correction. It is presumably the success of recognising a
      familiar object (a face) which overrides the correction of convergence. This
      suggests that the brain strives for a congruency of eye vergence and distance
      perception.

PMID- 17455760
TI  - Dynamic grouping and interpolation induced by flickering stimuli.
AB  - A novel grouping and interpolation effect induced by flickering stimuli is
      described: a matrix of flickering elements forms stick-like clusters, then the
      clusters gradually dissociate back into the discrete elements within a few
      seconds. On continuous viewing, this flicker-induced grouping and interpolation
      repeatedly disappeared and reappeared. The perceived strength of this phenomenon
      peaked when the luminance of the flickering elements was alternately darker and
      lighter than the background; thus, the reversal of the luminance contrast
      polarity was responsible for flicker-induced grouping. The temporal dynamics of
      flicker-induced grouping showed the stochastic nature of perceptual alternation,
      which depended on the global structure of the stimulus. From these results, it is
      concluded that flicker-induced grouping reflects multiple stages of visual
      processing.

PMID- 17455761
TI  - The Leaning Tower illusion: a new illusion of perspective.

PMID- 17455762
TI  - Patho-biotechnology; using bad bugs to make good bugs better.
AB  - Given the increasing commercial and clinical relevance of probiotic cultures,
      improving their stress tolerance profile and ability to overcome the
      physiochemical defences of the host is an important biological goal. Pathogenic
      bacteria have evolved sophisticated strategies to overcome host defences,
      interact with the immune system and interfere with essential host systems. We
      coin the term 'patho-biotechnology' to describe the exploitation of these
      valuable traits in biotechnology and biomedicine. This approach shows promise for
      the design of more technologically robust and effective probiotic cultures with
      improved biotechnological and clinical applications as well as the development of
      novel vaccine and drug delivery platforms.

PMID- 17455763
TI  - Cold shock proteins aid coupling of transcription and translation in bacteria.
AB  - Transcription and translation are tightly coupled in bacterial cells. However,
      the transcription machinery and ribosomes generally occupy different subcellular
      regions in bacteria such as Escherichia coli and Bacillus subtilis, indicating
      the need for (a) mechanism(s) coupling these processes. A prime function of this
      mechanism(s) would be ensuring the transfer of unfolded mRNA from the nucleoid to
      ribosomes, which require linear mRNA for the initiation of translation. During
      conditions of a sudden decrease in temperature (cold shock), secondary structures
      in mRNA would pose an even greater problem for the initiation process. Two
      conserved classes of proteins, cold shock proteins (CSPs) and cold induced RNA
      helicases (CSHs), appear to be major players in the prevention of secondary mRNA
      structures and in transcription/translation coupling. CSPs are general mRNA
      binding proteins, and like CSH-type RNA helicases, the presence of at least one
      csp gene in the cell is essential for viability. Members of both protein families
      have recently been shown to interact, suggesting that a two-step process achieves
      the coupling process, removal of secondary mRNA structures through CSHs and
      prevention of reformation through CSPs.

PMID- 17455764
TI  - Current molecular techniques for the detection of microbial pathogens.
AB  - Traditionally the detection of microbial pathogens in clinical, environmental or
      food samples has commonly needed the prelevation of cells by culture before the
      application ofthe detection strategy. This is done to increase cell number
      thereby overcoming problems associated with the sensitivity of classical
      detection strategies. However, culture-based methods have the disadvantages of
      taking longer, usually are more complex and require skilled personnel as well as
      not being able to detect viable but non cultivable microbial species. A number of
      molecular methods have been developed in the last 10 to 15 years to overcome
      these issues and to facilitate the rapid, accurate, sensitive and cost effective
      identification and enumeration of microorganisms which are designed to replace
      and/or support classical approaches to microbial detection. Amongst these new
      methods, ones based on the polymerase chain reaction and nucleic acid
      hybridization have been shown to be particularly suitable for this purpose. This
      review generally summarizes some of the current and emerging nucleic acid based
      molecular approaches for the detection, discrimination andquantification
      ofmicrobes in environmental, food and clinical samples and includes reference to
      the recently developing areas of microfluidics and nanotechnology "Lab-on-a
      chip".

PMID- 17455765
TI  - State of the art of fusion of computed tomography data and optical 3D images.
AB  - When three-dimensional imaging is necessary in dentistry, oral surgery or
      maxillofacial surgery, conventional computed tomography or cone beam computed
      tomography is chosen regularly. However, there are two obvious drawbacks.
      Metallic restorations lead to pronounced streak artefacts in conventional
      computed tomography. Moreover, the resolution of both conventional computed
      tomography and cone beam computed tomography is limited to 0.3 mm. This
      resolution is not sufficient for the fabrication of dental restorations. In order
      to improve the quality of the two different computed tomography techniques and to
      eliminate streak artefacts, fusion with optical 3D images can be considered. The
      resolution of optical 3D images can reach the range of some microms depending on
      the calibration of the sensor. Metal artefacts do not occur. The fusion of
      computed tomography images without artefacts and optical 3D images leads to a
      mean deviation of corresponding points for the two imaging techniques of 0.1262
      +/- 0.0301 mm. When computed tomography images with metal artefacts are used, the
      deviation increases up to 0.2671 +/- 0.0580 mm. The accuracy of image fusion is
      significantly reduced by metal artefacts (p < 0.0005). When image fusion of
      computed tomography and optical 3D images is used in clinical studies, the mean
      deviation of corresponding points for the two imaging techniques for mandible and
      maxilla is 0.66 +/- 0.49 mm and 0.56 +/- 0.48 mm, respectively. The available
      data on image fusion show that the quality of computed tomography data without
      streak artefacts can be significantly improved by registration with optical 3D
      images. The precision of the fused images exceeds the resolution of the original
      computed tomography. When streak artefacts are present, image fusion makes it
      possible to increase the quality of the data to the level of the original
      resolution of computed tomography without artefacts.

PMID- 17455766
TI  - Computer-aided analysis of the biomechanics of tooth movements.
AB  - Orthodontic biomechanics started in the early 1960s with the work of Burstone and
      later Nikolai. Experimental and theoretical studies using finite element methods
      (FEM) focused on the determination of the position of the center of resistance of
      single and multi-rooted teeth. Due to the complex structure of the system
      tooth/periodontal ligament/alveolar bone and because of the limited power of
      computers, the first numerical models were quite simple. Improved FE software,
      sophisticated programs for model generation and the explosion of computer power
      in the last decade resulted in more complex tooth-periodontium models and model
      assumptions. This paper describes the application of finite element methods in
      orthodontic biomechanics with the help of several typical examples. The examples
      cover aspects from basic orthodontic biomechanics to possible future applications
      in treatment planning using bone remodelling theories: determination of the
      mechanical properties of the periodontal ligament in a combined numerical and
      experimental study, calculation of the centers of resistance of different teeth,
      and simulation of orthodontic tooth movements. The examples show that nowadays
      finite element methods are a useful and easy-to-handle tool for the solution of a
      larger number of structure-mechanical and biomechanical problems. Nevertheless,
      in spite of the enormous technical progress in the last decade, many problems in
      orthodontic biomechanics remain to be solved.

PMID- 17455767
TI  - Applications of three-dimensionally scanned models in orthodontics.
AB  - The purpose of this study was to investigate clinical applications of the three
      dimensional reverse engineering technologies for the analysis of orthodontic
      models. The measuring accuracy and the process of the 3D model scanning technique
      were evaluated with respect to linear, surface and volumetric parameters.
      Orthodontically induced dentoalveolar changes, which have been traditionally
      evaluated by cephalometric analysis, were assessed by the registration function
      of Rapidform 2002, a 3D-reverse modeling software in scanned maxillary casts.
      Three-dimensional digital models are valuable alternatives to conventional casts
      for model analysis and also yield information which could previously be gathered
      only by cephalometric superimposition.

PMID- 17455768
TI  - SureSmile--CAD/CAM system for orthodontic treatment planning, simulation and
      fabrication of customized archwires.
AB  - SureSmile is an all-digital system which uses new 3-D imaging and computer
      techniques for diagnostics and treatment planning and uses robotics to customize
      fixed orthodontic appliances. Treatment can be simulated in advance and different
      treatment strategies can be visualized; this allows detailed treatment planning.
      The application of CAD/CAM aims at improving reproducibility, efficiency, and
      quality of orthodontic treatment.

PMID- 17455769
TI  - Patient images on the internet: a platform for the communication between
      orthodontic clinics.
AB  - Certain diagnostic tools (eg, extra- and intraoral photographs, orthopantogram,
      lateral radiograph and model photos) are necessary at the start and during the
      course of an orthodontic treatment. These tools can now be shared with other
      medical professionals (eg, oral surgeon, dentist and orthodontist) involved in
      the treatment of a particular patient via the internet. This program creates
      better communication among the professionals concerned. The records of the
      patient are protected by a user name and a password. They make it possible for
      the patient to have access to his/her personal records at any time to see the
      progress of his/her treatment. This way, a patient can identify with the
      treatment, which should consequently improve the motivation and cooperation of
      the patient.

PMID- 17455770
TI  - Cerec standard 3-d occlusal contouring in comparison with the new biogeneric
      occlusal morphing: a case report.

PMID- 17455771
TI  - From blue to white: new high-strength material for Cerec--IPS e.max CAD LT.

PMID- 17455772
TI  - Efficient dynamic registration technique using metalbite presented with a Cerec
      3D partial crown: a case description.
AB  - Restoration of a mandibular first molar with an all-ceramic partial crown in a
      single treatment session is described in the present case. The Cerec 3D system
      (Sirona) was used with biogeneric technology.

PMID- 17455773
TI  - VITA CAD-Temp for inLab and Cerec 3D.
AB  - VITA CAD-Temp is a composite block which enables high-quality provisional
      restorations to be created using the Sirona milling units. The new Cerec MC XL
      and inLab MC XL units are the preferred choice on account of their significantly
      higher milling speeds. The technical requirements are described and an
      illustrated practical example presented. CAD-Temp constitutes a good example of
      rapid and efficient collaboration between dentists and dental technicians. This
      is illustrated on the basis of an example relating to the field of implant
      prosthetics.

PMID- 17455774
TI  - CAD/CAM paving the way for modern all-ceramic application in the dental practice.

PMID- 17455775
TI  - Biogeneric and user-friendly: the Cerec 3D software upgrade V3.00.
AB  - The new software for Cerec and inLab represents a new milestone in terms of
      occlusal surface design and ease of use. The graphical user interface has been
      streamlined and visually enhanced. All the functions intended for experienced
      users have been grouped together under the menu item "Master mode". The software
      now provides an occlusal-surface design function based on the biogeneric tooth
      model developed by Professors A. Mehl and V. Blanz. This function is superior to
      traditional methods.

PMID- 17455776
TI  - No compromises the new CEREC MC XL and inLab MC XL milling machines.
AB  - Cerec 3 and inLab will soon be augmented by the new CEREC MC XL and inLab MC XL
      milling machines. Dentists and dental technicians who are on the threshold of
      introducing CAD (Computer Aided Dentistry) to their practice or laboratory can
      either opt for a low-cost solution or for a system which offers an extended range
      of indications as well as enhanced reliability and ease of use. The Cerec 3 and
      inLab milling machines are well-tried, accepted and proven. They offer an
      interesting balance between price and performance. The MC XL series is not only
      faster and more precise, but is also quieter and easier to use.

PMID- 17455777
TI  - Sirona CEREC Blocs and inCoris.
AB  - Unfortunately, there is no such thing as a universal material for every
      application--neither in engineering nor in dentistry. Instead, it is a matter of
      selecting the right material for each individual case and deploying this material
      in the appropriate way. For this reason, Sirona Dental Systems has decided to
      augment the existing product portfolio of its material suppliers (Vita Zahnfabrik
      and Ivoclar Vivadent) and has launched its own range of ceramics for chairside
      applications, as well as for the fabrication of crowns and bridges in dental
      laboratories.

PMID- 17455778
TI  - Work in progress: the web portal that brings together Cerec users and inLab
      laboratories--moving towards the impression-free dental practice.
AB  - Thanks to the compatibility of Cerec and inLab, the "impression-free" dental
      practice is just around the corner. Some final details remain to be clarified. An
      easy-to-use web portal is under development.

PMID- 17455779
TI  - Preventing peanut allergy.

PMID- 17455780
TI  - Home dialysis can improve quality of life.

PMID- 17455781
TI  - Renal stone recurrence can be prevented.

PMID- 17455782
TI  - Early recognition the key to CKD.

PMID- 17455783
TI  - Tackling the QOF2 indicators for CKD.

PMID- 17455784
TI  - Managing wound problems following joint replacement.

PMID- 17455785
TI  - Psoriasis.

PMID- 17455787
TI  - Activity of translation system and abundance of tmRNA during development of
      Streptomyces aureofaciens producing tetracycline.
AB  - Transition from exponential phase of growth to stationary phase in Streptomyces
      aureofaciens is characterized by a decrease in the rate of translation and
      induction of tetracycline (Ttc) biosynthesis. In exponential phase, no
      significant changes were found in the activity of ribosomes at binding of ternary
      complex Phe-tRNA.EF-Tu.GTP to the A-site on ribosomes. Overexpression of Ttc in
      stationary phase is accompanied by a decrease in the binding of the ternary
      complex Phe-tRNA.EF-Tu.GTP to the A-site of ribosome and a formation of an
      aggregate with Ttc by part of the ribosomes. Antibiotics that cause ribosome to
      stall or pause could increase the requirement for tmRNA in the process called
      trans-translation. We found differences in the level of tmRNA during the
      development of S. aureofaciens. Subinhibitory concentrations of Ttc, streptomycin
      and chloramphenicol induced an increase in the tmRNA level in cells from the
      exponential phase of growth. In vitro trans-translation system of S. aureofaciens
      was sensitive to Ttc at a concentration of > 15 micromol/L; the trans-translation
      system can thus be considered to contribute to resistance against Ttc produced
      only at sublethal concentrations. These experiments suggest that the main role of
      the rising tmRNA level at the beginning of the Ttc production is connected with
      ribosome rescue.

PMID- 17455788
TI  - Factors affecting the outcome of the acidification power test of yeast quality:
      critical reappraisal.
AB  - Brewery bottom yeast strain 95 from the Pilsner Urquell propagation unit was used
      to reappraise the efficiency of the acidification power (AP) test consisting in
      determining the spontaneous (oxygen-induced) and glucose-induced medium
      acidification caused by yeast and lactic acid bacteria under standard conditions,
      and used widely for assessing and predicting the vitality of industrial strains.
      AP was evaluated in yeast stored for different periods of time (0-28 d) at 4
      degrees C, at different temperatures before and during the test (0-55 degrees C),
      and at different concentrations of cells and glucose and different cells-to
      glucose ratios. All these factors had a strong effect on acidification kinetics
      and the AP value. By contrast, the duration of the lag period between yeast
      collection and the test (0-6 h) had no perceptible effect on the AP value. The
      best results were achieved at saturation concentrations of cells (> 10 g pressed
      yeast or approximately 14 g yeast slurry per 100 mL) and glucose (approximately 3
      %) and at 25 degrees C. Since an exact evaluation of acidification
      characteristics depends strongly on the kinetics of the process, the AP test
      should include monitoring the time course of the acidification.

PMID- 17455789
TI  - Analysis of the presence of prtR proteinase gene in natural isolates of
      Lactobacillus rhamnosus.
AB  - The region of the prtR gene coding for the active site of PrtR proteinase was
      detected in natural isolates of lactobacilli, previously determined as
      Lactobacillus rhamnosus. This region was present in all L. rhamnosus strains with
      proteolytic activity. The PCR primers used were constructed on the basis of the
      sequence of the catalytic domain of the prtR proteinase gene. These primers
      generated in colony-PCR procedure specific 611 1-bp product with DNA from natural
      isolates of L. rhamnosus. No PCR amplifications using these primers were obtained
      for closely related bacteria of genus Lactobacillus, regardless of their
      proteolytic activity. In addition, these primers could be used singly or in
      multiplex PCR together with the Lactobacillus genus-specific primers. Compared
      with the other proteinases within the genus Lactobacillus (PrtP, PrtB and PrtH)
      which retained the activity in cell-free proteinase extracts, PrtR proteinase
      showed proteolytic activity only under in vivo conditions (whole cells of the
      producing strains).

PMID- 17455790
TI  - Aspergillus niger pH 2.1 optimum acid phosphatase with high affinity for phytate.
AB  - An extracellular acid phosphatase isolated from the culture of a wild strain
      Aspergillus niger, producing the dephosphorylating 3-phytase, was obtained in a
      homogeneous form by sequential application of ultrafiltration through PS 50
      membrane, gel filtration on Sephadex G-100 and ion exchange chromatography on
      DEAE-Sepharose CL 6B and CM-Sepharose CL 6B. The enzyme showed a maximum
      catalytic value in a strongly acidic range (pH 2.0-2.4) with pHopt 2.1 and topt
      66 degrees C. The acid phosphatase showed a wide substrate specificity and a high
      affinity for sodium phytate, 2.5x higher than with 4-nitrophenyl phosphate. This
      property of the acid phosphatase demonstrated that it is a potent 3-phytase at pH
      2.1 and is of great significance for a practical application of the
      dephosphorylating complex--its addition to the diets of monogastric animals in
      view of the low pH values in the digestive tract.

PMID- 17455791
TI  - Comparative studies of differential expression of chitinolytic enzymes encoded by
      chiA, chiB, chiC and nagA genes in Aspergillus nidulans.
AB  - N-Acetyl-D-glucosamine, chito-oligomers and carbon starvation regulated chiA,
      chiB, and nagA gene expressions in Aspergillus nidulans cultures. The gene
      expression patterns of the main extracellular endochitinase ChiB and the N-acetyl
      beta-D-glucosaminidase NagA were similar, and the ChiB-NagA enzyme system may
      play a morphological and/or nutritional role during autolysis. Alterations in the
      levels of reactive oxygen species or in the glutathione-glutathione disulfide
      redox balance, characteristic physiological changes developing in ageing and
      autolyzing fungal cultures, did not affect the regulation of either the growth
      related chiA or the autolysis-coupled chiB genes although both of them were down
      regulated under diamide stress. The transcription of the chiC gene with unknown
      physiological function was repressed by increased intracellular superoxide
      concentration.

PMID- 17455792
TI  - The fission yeast ortholog of eIF3a subunit is not functional in Saccharomyces
      cerevisiae.
AB  - The Schizosaccharomyces pombe eIF3a ortholog (SpeIF3a) was shown to be unable to
      substitute for S. cerevisiae eIF3a (SceIF3a) in its essential function in the
      initiation of translation. Overproduction of SpeIF3a altered the distribution of
      SceIF3a but formation of the endogenous eIF3 complex was not affected. SpeIF3a
      was found to be more tightly bound to S. cerevisiae ribosomes than SceIF3a and
      other eIF3 subunits (eIF3g, eIF3i, eIF3j). The host cells displayed aberrant
      morphology and altered chitin deposition. SpeIF3a probably competes with SceIF3a
      for binding to either ribosomes or yet to be identified substrates.

PMID- 17455793
TI  - Motility in Oscillatoria salina as affected by different factors.
AB  - All 3-10-d-old Oscillatoria salina filaments glide with the speed of 323-330
      microm/min (BG 11 medium, pH 7.5, 21 +/- 2 degrees C, continuous light intensity
      of approximately 30 micromol m(-2) s(-1)) in a culture chamber. However, a time
      bound progressive decrease in gliding speed and in percentage of gliding
      filaments occurred, depending upon the severity of different stress factors
      studied, viz. water stress (2-8% agarized media, liquid media with 0.2-1 mol/L
      NaCl, blot-dryness of filaments for > or = 5 min), temperature shock (5, 40
      degrees C for > or = 5 min; 35 degrees C for > or = 15 min), darkness and low
      light intensity (2, 10 micromol m(-2) s(-1)), UV exposure (0.96-3.84 kJ/m2), pH
      extremes (< or = 6.5 and > or = 9.5), lack of all nutrients from liquid medium
      (double distilled water), presence of 'heavy' metals (1, 25 ppm Fe, Cu, Zn, Ni,
      Co, Hg) or organic substances in liquid medium (25, 250 ppm 2,4-D, captan, urea,
      DDT, thiourea). This feature of the alga (i.e. reduction in speed and percentage
      of gliding filaments depending upon severity of stress conditions) may thus be
      suggested to be used in assessing water quality.

PMID- 17455794
TI  - The role of Mn-dependent peroxidase in dye decolorization by static and agitated
      cultures of Irpex lacteus.
AB  - Dye decolorization capacity of two white-rot fungi, Irpex lacteus and
      Phanerochaete chrysosporium, was compared in N-limited liquid cultures. The
      agitated cultures showed lower ability to decolorize azo dyes Reactive Orange 16
      and Naphthol Blue Black than static cultures. Similar effect was also observed
      with other structurally different synthetic dyes. The effect of surfactants on
      the decolorization process is discussed. A significant increase in the Reactive
      Orange 16 decolorization by the agitated I. lacteus cultures was observed after
      adding 0.1% Tween 80, following a higher Mn-dependent peroxidase production. The
      in vitro dye decolorization using the purified enzyme proved its decolorization
      ability.

PMID- 17455795
TI  - Production of lignocellulose-degrading enzymes and changes in soil bacterial
      communities during the growth of Pleurotus ostreatus in soil with different
      carbon content.
AB  - The extracellular enzyme activity and changes in soil bacterial community during
      the growth of the ligninolytic fungus Pleurotus ostreatus were determined in
      nonsterile soil with low and high available carbon content. In soil with P.
      ostreatus, the activity of ligninolytic enzymes laccase and Mn-peroxidase was
      several orders of magnitude higher than in soil without the fungus. Addition of
      lignocellulose to soil increased the activity of cellulolytic fungi and the
      production of Mn-peroxidase by P. ostreatus. The counts of heterotrophic bacteria
      were more significantly affected by the presence of lignocellulose than by P.
      ostreatus. The effects of both substrate addition and time (succession) were more
      significant factors affecting the soil bacterial community than the presence of
      P. ostreatus. Bacterial community structure was affected by fungal colonization
      in low carbon soil, where a decrease of diversity and changes in substrate
      utilization profiles were detected.

PMID- 17455796
TI  - The impact of acrylonitrile and bioaugmentation on the biodegradation activity
      and bacterial community structure of a topsoil.
AB  - The analysis of the bacterial community within the soil using DGGE showed
      acrylonitrile (ACN) could lead to the selection of significantly similar
      communities. Moreover, Rhodococcus sp. AJ270 was successfully established in the
      soil community. High GC G+-bacteria also responded positively to ACN addition.
      Bioaugmentation or carbon addition had no impact on the rate or degree of ACN
      degradation. ACN could be readily degraded by the soil bacteria, however, the
      community structure was significantly affected by its addition as well as by the
      addition of carbon or Rhodococcus sp. AJ270. The bioaugmentation of the soil with
      this strain was successful, in that the organism became established within the
      community. ACN addition to a soil produces statistically significant changes in
      the bacterial community.

PMID- 17455797
TI  - Cerebrospinal-fluid profile in neuroborreliosis and its diagnostic significance.
AB  - Selected cerebrospinal-fluid (CSF) parameters (intrathecal synthesis of Borrelia
      specific antibodies, oligoclonal IgG bands, CSF-to-serum quotient of albumin as a
      marker of blood-CSF barrier function and cytology) and typical CSF profile in
      neuroborreliosis were evaluated with the aim of elucidating possible clinical and
      laboratory similarities of neuroborreliosis (NB) and other neurological diseases
      (OND). From the cohort of 58 patients (38 diagnosed for NB, 20 with OND) NB
      patients had positive Borrelia-specific IgG antibodies in 97 % and positive
      Borrelia-specific IgM antibodies in 55 %; oligoclonal IgG bands were detected in
      55%. The blood-CSF barrier was impaired in 89%, positive cytology was detected in
      97% of the NB patients. Evaluation of specific intrathecal synthesis improves CSF
      diagnosis of NB, therefore, a combined CSF analysis has to be considered along
      with the clinical picture and medical history when formulating the diagnosis of
      NB.

PMID- 17455798
TI  - Campylobacter sepsis with multiple organ failure in IgG subclass deficiency.
AB  - Some patients with immunodeficiency develop clinical features of autoimmune
      disorders. A previously asymptomatic antibody deficiency can underlie the
      development of autoimmune diseases and a severe course of infection, with a risk
      of sepsis; such cases are known in selective IgA deficiency. On the other hand,
      little information is available on selective IgG subclass deficiencies. An
      unexpectedly severe course of Campylobacter infection in a 19-year-old woman with
      a previously undiagnosed complex immune disorder, including selective IgG1
      immunodeficiency, Hashimoto's autoimmune thyroiditis with hypothyroidism combined
      with Addison's disease presumably due to autoimmune adrenalitis, autoimmunity and
      allergy is described. The pathophysiological mechanisms of autoimmunity in latent
      humoral defects are discussed.

PMID- 17455799
TI  - Prevention of infection transmission during stem cell transplantation.
AB  - Group of 152 patients (investigated before autologous transplantation) and 35
      healthy donors for allogeneic transplantation was examined for the risk of
      infection transmission that can be associated with the infusion of cryopreserved
      peripheral blood progenitor cells to the patient and/or cross-contamination of
      stored grafts. No laboratory signs of active infection were found in 22 donors
      (63 %) and in 91 patients (60%). The most common was active infection by herpes
      viruses--50 cases in patients, 21 cases in donors; hepatitis B was found in only
      two cases. The rate of clinically unsuspected (but dangerous) infections in
      donors and patients thus remains relatively high in spite of the fact that the
      system of donor search and the whole transplantation procedure have improved in
      the last years. The system of safety assurance is extremely important and the
      whole palette of preventive tests according to EBMT (European Blood and Marrow
      Transplantation Group) and ISHAGE (International Society for Hemotherapy and
      Graft Engineering) is fully justified.

PMID- 17455800
TI  - Superantigen types in Staphylococcus aureus isolated from patients with cystic
      fibrosis.
AB  - The screening of 17 SAg genes of S. aureus isolated from the sputum of cystic
      fibrosis (CF) patients revealed that among 47 genetically different strains, 39
      (83 %) carried SAg genes. Superantigens forming enterotoxin gene cluster were
      detected in 20 strains. The 2nd most common superantigen type was selk detected
      in 13 strains. In 9 strains, selk occurred together with the sea gene. Out of 74
      strains recovered from nasal carriers, 56 (75 %) were found to carry SAg genes,
      38 carried egc genes, while selk was detected in 5 strains. The predominant SAg
      types in both investigated S. aureus populations were egc and selk/sea, but selk
      gene frequency was significantly higher in the CF-derived strains.

PMID- 17455801
TI  - Retrospective sequence analysis of the human PRNP gene from the formaldehyde
      fixed paraffin-embedded tissues: report of two cases of Creutzfeldt-Jakob
      disease.
AB  - The definitive diagnosis of the CJD (Creutzfeldt-Jakob disease; very rare
      neurodegenerative disorder) can be established only on the basis of post-mortem
      examination of the central nervous system tissue. Formaldehyde-fixed paraffin
      embedded (FFPE) tissue samples may thus constitute the only material available
      for molecular pathology analyses. We performed post-mortem analysis of the coding
      region of the prion-protein gene (PRNP)-sequence variations in two definite CJD
      cases suggestive of genetic form. Only FFPE tissues were available for molecular
      analyses. The PRNP gene open reading frame was amplified from the genomic DNA
      (FFPE isolated) in four overlapping, two round semi-nested PCR products that were
      directly sequenced. We found known pathogenic sequence variation g.532 G>A
      (Asp178Asn) in patient 1 but we did not find any pathogenic sequence variation in
      patient 2 despite her origin from the Slovak Orava region. Based on these
      results, we were able to discriminate between genetic and sporadic form of CJD in
      patient 1 and 2, respectively. The established method was found to be efficient
      for the sequence-variation analysis of the entire PRNP gene coding region using
      the genomic DNA isolated from the FFPE tissues; it can be employed in other
      retrospective molecular studies.

PMID- 17455802
TI  - The mechanisms of activation of normal human serum complement by Escherichia coli
      strains with K1 surface antigen.
AB  - Ten E. coli K1 strains isolated from the urine of children with urinary tract
      infections were sensitive to the bactericidal action of normal human serum (NHS).
      The role of the particular mechanisms of complement activation was determined in
      the process of killing these strains, showing variable sensitivity to the
      bactericidal action of NHS; three mechanisms of activation of human complement
      were observed. Important role of alternative pathway activation in the
      bactericidal action of NHS against E. coli K1 strains independent of the
      classical and lectin pathways was not established.

PMID- 17455803
TI  - Clinical pseudomonas aeruginosa: potential factors of pathogenicity and
      resistance to antimicrobials.
AB  - Resistance to 17 antimicrobials, surface hydrophobicity, motility, biofilm,
      production of N-acylhomoserine lactone signal molecules (N-butyrylhomoserine
      lactone and N-3-oxolauroylhomoserine lactone) and response to oxidative stress
      were analyzed in 47 clinical Pseudomonas aeruginosa strains. In addition to
      natural resistance, the strains demonstrated the greatest level of resistance to
      cefotaxime (91.5%). Isolates in the range of 44.7-57.4% were resistant to
      aminoglycosides and ciprofloxacin, of 25.5-36.2% to cephalosporins. On the other
      hand, 97.9% remained susceptible to meropenem, 93.6% to piperacillin + tazobactam
      and 87.2% to piperacillin. The majority of the strains (72.3%) manifested their
      hydrophilic character. Higher zones of motility showed 12 isolates (in average
      54.8 mm) as compared to the others (30.2 mm). Approximately 1/3 of the strains
      (29.8%) produced a higher amount of biofilm quantified by measuring the
      absorbance of solubilized crystal violet (0.20-0.46) than the rest of isolates (0
      0.19). All but two strains produced N-3-oxolauroylhomoserine lactone and in 48.9%
      of samples N-butyrylhomoserine lactone were detected. Only four isolates with
      higher biofilm production showed both types of homoserine lactone. Majority of
      the strains (70.2%) manifested higher resistance to H2O2 than the rest of the
      strains. The group of strains resistant to aminoglycosides and ciprofloxacin
      revealed a significantly higher number of hydrophobic strains (compared with the
      sensitive ones). In contrast, higher number of strains sensitive to
      aminoglycosides and ciprofloxacin or only to ciprofloxacin produced N
      butyrylhomoserine lactone and biofilm (compared to the resistant ones). Such
      association was not found among the rest of the tested parameters. The results
      indicate that the resistance to antimicrobials in P. aeruginosa isolates was not
      generally associated with changes in the production of the pathogenicity factors.

PMID- 17455804
TI  - Development of specific and rapid detection of bacterial pathogens in dairy
      products by PCR.
AB  - A simple and specific method for direct detection of bovine mastitis pathogens
      (Streptococcus agalactiae (GBS), Staphylococcus aureus and Escherichia coli) in
      milk products, bacterial samples from milk and isolated bacterial DNA was
      developed. The method is based on polymerase chain reaction (PCR) using sequence
      specific primers only for GBS and species-specific primers derived from 16S and
      23S rRNA for all chosen species. The presence of the gene of surface immunogenic
      protein (Sip) in bovine GBS isolates, described previously only in human GBS
      isolates was confirmed. The GBS detection was performed with the sequence coding
      for surface immunogenic protein from GBS human isolates designated as Sip
      specific sequence (SSS); this sequence was selected for specific primer design.
      The sequence is unique for GBS and was designed from a consensus of all known sip
      genes. The specific identification was shown on a collection of 75 GBS bovine
      isolates from different localities in Slovakia. All isolates were positive to
      SSS, 16S and 23S rRNA sequence. The 16S and 23S rRNA PCR detection was also
      performed with S. aureus and E. coli isolates and specific PCR products were also
      detected. The detection limit of this assay for milk products was 6 CFU/microL
      (i.e. 6000 CFU/mL) for GBS and E. coli, and 16 CFU/microL for S. aureus. This
      rapid, sensitive and specific diagnostic method can be performed within hours and
      represents an innovative diagnostic tool for the detection of milk pathogens in
      dairy products.

PMID- 17455805
TI  - Toll-like receptor gene polymorphism and its relationship with somatic cell
      concentration and natural bacterial infections of the mammary gland in sheep.
AB  - Possible correlation between Toll-like receptor (TLR)-gene mutations and the
      susceptibility of the mammary gland to bacterial infections and also the
      associate breed-dependent aspects of somatic cell concentration (SCC), bacterial
      infection and TLR-gene mutations in sheep are described. In Polish Lowland Sheep
      (PLS), milk samples exceeding the level of 500/microL (i.e. 5 x 10(5) per mL) of
      SCC were recorded almost twice more frequently than in Polish Heath Sheep (PHS)
      (40 and 22.3%, respectively). The frequency of bacterial infections was also
      found in a similar ratio (20 and 12.7%, respectively). During detection of the
      TLR-gene mutation we recorded 2 alleles of TLR1, 6 alleles of TLR2 and 10 alleles
      of TLR4 genes in PHS sheep, while PLS sheep possessed 2, 4 and 6 alleles,
      respectively. Statistical analyses revealed a relationship between the specified
      TLR alleles, SCC and the frequency of incidence of bacterial inflammations of
      mammary gland. The data may serve as a benchmark for further study of TLR-gene
      mutation-dependent predisposition of mammary gland defensive cells to recognize
      the pathogen properly and initiate the immunological response, and may help in
      identifying one of the markers of natural resistance against sheep mastitis.

PMID- 17455806
TI  - Detection of Borrelia burgdorferi sensu lato and Chlamydophila psittaci in throat
      and cloacal swabs from birds migrating through Slovakia.
AB  - We have screened 91 migratory birds representing 32 species during the autumn of
      2003 for the presence of the zoonotic pathogens Borrelia and Chlamydophila. Using
      polymerase chain reaction (PCR), B. burgdorferi sensu stricto was detected in
      cloacal swabs and, in two causes, also in throat swabs in 8 individuals (8.7 %)
      representing 7 birds species; B. garinii and B. afzelii were not detected. C.
      psittaci was detected only in cloacal swabs; 6 birds (6.6 %) from four species
      were found to be positive. The PCR products were sequenced and the sequences were
      compared phylogenetically with the gene sequences of 14 Chlamydophila strains
      retrieved from nucleotide databases; although the sequenced DNA was only 110 bp
      long, all obtained sequences created a new cluster with sublines branching from a
      position close to the periphery of the genus. All tested samples appear distinct
      within the known species and were most similar to C. felis or C. abortis.

PMID- 17455807
TI  - Immunological and central nervous system changes in mice suffering from
      Staphyloccocus aureus and treated with Saccharomyces cerevisiae var. vini living
      cells.
AB  - The influence of Saccharomyces cerevisiae var. vini viable cells on the
      Staphylococcus aureus-suffering mice was ascertained: (1) effect of S. aureus
      living cells on antibacterial and antitoxic antibodies, (2) effect of S. aureus
      on the number of neurons and macroglial cells in different areas of mouse
      hippocampus, (3) effect of S. cerevisiae var. vini viable cells on the above
      mentioned changes of immune and nervous system. Treatment with S. cerevisiae var.
      vini provokes immune stimulation and change of the total number of macroglial
      elements in the CA1 field of hippocampus.

PMID- 17455809
TI  - Perceptions of the impact of primary care organizations on GP prescribing: the
      iron fist in the velvet glove?
AB  - PURPOSE: This qualitative study aims to examine key stakeholders' perspectives of
      primary care group/trust prescribing strategies. Within the context of general
      practice prescribing, the paper also debates the wider issue of whether GPs'
      prescribing autonomy is under threat from managerial expansion following recent
      organisational changes in primary care. DESIGN/METHODOLOGY/APPROACH: Data were
      obtained from focus groups and a series of individual semi-structured interviews
      with GPs and key primary care organisation stakeholders. FINDINGS: The data
      underlie a tension between the managerial objective of cost-restraint and GPs'
      commitment to quality improvement and individual clinical patient management. In
      presenting both managerial and medical narratives, two divergent and often
      conflicting discourses emerge, which leads to speculation that managerial
      attempts to constrain prescribing autonomy will achieve only limited success. The
      contention is that GPs' discourse features as a challenge to a managerial
      discourse that reflects attempts to regulate, standardise and curtail clinical
      discretion. This is due not only to GPs' expressed hegemonic ideals that clinical
      practice centres on the interests of the individual patient, but also to the fact
      that the managerial discourse of evidence-based medicine encapsulates only a
      limited share of the knowledge that GPs draw on in decision making. However,
      while managers' discourse presented them as unwilling to impose change or
      directly challenge clinical practice, evidence also emerged to suggest that is
      not yet possible to be sufficiently convinced of the future retention of
      prescribing autonomy. On the other hand, the use of peer scrutiny posed an
      indirect managerial influence on prescribing, whilst the emergence of prescribing
      advisors as analysts of cost-effectiveness may threaten doctors' dominance of
      medical knowledge. RESEARCH LIMITATIONS/IMPLICATIONS: There is a continuing need
      to analyse the impact of the new managerial reforms on primary care prescribing.
      ORIGINALITY/VALUE: This study provides a snapshot of managerial and GP relations
      at a time of primary care transition.

PMID- 17455808
TI  - Structure and functions of hepatitis C virus proteins: 15 years after.
AB  - Since its discovery in 1988, the hepatitis C virus (HCV) has become a hot topic
      of research by many groups around the world. This globally spread infectious
      agent is responsible for a large proportion of chronic viral hepatitides. The
      clue to halting the hepatitis C pandemic may be the detailed understanding of the
      virus structure, its replication mechanism, and the exact functions of the
      various proteins. Such understanding could enable the development of new
      antivirals targeted against hepatitis C virus and possibly an effective vaccine.
      This review recaps the current knowledge about the HCV genome 15 years after its
      discovery. The structure and function of particular viral structural (core, E1,
      E2) and nonstructural (NS2, NS3, NS4, NS5) proteins and noncoding regions known
      to date are described. With respect to frequent conflicting reports from
      different research groups, results reproducibly demonstrated by independent
      investigators are emphasized. Owing to many obstacles and limitations inherent in
      doing research on this noteworthy virus, the current knowledge is incomplete and
      the answers to many important questions are to be expected in the future.

PMID- 17455810
TI  - Effects of dialogue groups on physicians' work environment.
AB  - PURPOSE: The purpose of this study is to evaluate whether dialogue groups for
      physicians can improve their psychosocial work environment.
      DESIGN/METHODOLOGY/APPROACH: The study assessed the impact of eight dialogue
      groups, which involved 60 physicians at a children's clinic in one of the main
      hospitals in Stockholm. Psychosocial work environment measures were collected
      through a validated instrument sent to all physicians (n = 68) in 1999, 2001 and
      2003. Follow-up data were collected after the termination of the groups.
      FINDINGS: The overall score of organizational and staff wellbeing, as assessed by
      the physicians at the clinic, deteriorated from 1999 until 2003 and then improved
      2004. This shift in the trend coincided with the intervention. No other factors
      which might explain this shift could be identified. RESEARCH
      LIMITATIONS/IMPLICATIONS: In a naturalistic study of this kind it is not possible
      to prove any causal relationships. A controlled survey of management programmes
      concerning the work environment among physicians would be of interest for further
      research. PRACTICAL IMPLICATIONS: The results suggest that dialogue groups may be
      one way to improve the psychosocial work environment for physicians.
      ORIGINALITY/VALUE: There is a lack of intervention studies regarding the efficacy
      of management programmes directed toward physicians, concerning the effects on
      professional and personal wellbeing. This is the first time dialogue groups have
      been studied within a health care setting.

PMID- 17455811
TI  - A model for calculating costs of hospital-acquired infections: an Italian
      experience.
AB  - PURPOSE: Many approaches on the economic aspect of hospital acquired infections
      (HAIs) have two major limitations: first, the lack of distinction between
      resources attributable to the management of HAI and resources absorbed by the
      main clinical problem for which the patient was hospitalized, and second, the
      lack of an adequate method for calculating the relative costs. These assume that
      the resources used by HAI can be determined by measuring the extra days of length
      of days (LOS) of infected patients versus non-infected patients and attribute to
      extra-LOS a value to the mean total cost. The aim of the article is to test a
      cost-modelling method that could overcome these limitations by applying the
      appropriateness evaluation protocol to the medical charts of patients with
      hospital-acquired symptomatic urinary tract infection (UTI) or sepsis, and by
      using cost-centre accounting. DESIGN/METHODOLOGY/APPROACH: The paper explains and
      tests a model for calculating costs of HAIs. FINDINGS: The data analysis showed
      that it is not always true that infections protract LOS: five out of 25 sepsis
      cases have extra-LOS and eight out of 25 UTI cases have extra-LOS, while the
      cases of sepsis that arose in surgery ward and intensive care units and urinary
      tract infections in ICU are without prolongation of LOS. The data analysis also
      showed that, using the mean total cost, the three cases of sepsis in the general
      surgery and the six in the ICU did not incur costs, nor did the two cases of UTI
      in ICU, so that they appear to be infections at zero cost. Moreover, the weight
      of the cost for the bed, or for the diagnostic services, or for the
      pharmacological treatment, varied widely depending on the site of the HAI and the
      ward where the patient was hospitalized. ORIGINALITY/VALUE: The method can be
      applied in any hospital.

PMID- 17455812
TI  - Cancelled elective operations: an observational study from a district general
      hospital.
AB  - PURPOSE: Cancelled operations are a major drain on health resources: 8 per cent
      of scheduled elective operations are cancelled nationally, within 24 hours of
      surgery. The aim of this study is to define the extent of this problem in one
      Trust, and suggest strategies to reduce the cancellation rate.
      DESIGN/METHODOLOGY/APPROACH: A prospective survey was conducted over a 12-month
      period to identify cancelled day case and in-patient elective operations. A
      dedicated nurse practitioner was employed for this purpose, ensuring that the
      reasons for cancellation and the timing in relation to surgery were identified.
      The reasons for cancellation were grouped into patient-related reasons, hospital
      clinical reasons and hospital non-clinical reasons. FINDINGS: In total, 13,455
      operations were undertaken during the research period and 1,916 (14 per cent)
      cancellations were recorded, of which 615 were day cases and 1,301 in-patients:
      45 per cent (n = 867) of cancellations were within 24 hours of surgery; 51 per
      cent of cancellations were due to patient-related reasons; 34 per cent were
      cancelled for non-clinical reasons; and 15 per cent for clinical reasons. The
      common reasons for cancellation were inconvenient appointment (18.5 per cent),
      list over-running (16 per cent), the patients thought that they were unfit for
      surgery (12.2 per cent) and emergencies and trauma (9.4 per cent). PRACTICAL
      IMPLICATIONS: This study demonstrates that 14 per cent of elective operations are
      cancelled, nearly half of which are within 24 hours of surgery. The cancellation
      rates could be significantly improved by directing resources to address patient
      related causes and hospital non-clinical causes. ORIGINALITY/VALUE: This paper is
      of value in that it is demonstrated that most cancellations of elective
      operations are due to patient-related causes and several changes are suggested to
      try and limit the impact of these cancellations on elective operating lists.

PMID- 17455813
TI  - The impact of research governance in the United Kingdom on research involving a
      national survey.
AB  - PURPOSE: The purpose of this paper is to examine the impact that research
      governance processes in the National Health Service (NHS) are having on the
      conduct of research that involves a national survey and to point to ways that
      existing processes may develop to facilitate such research.
      DESIGN/METHODOLOGY/APPROACH: The paper describes the experiences of a research
      team of seeking approval in 357 NHS organisations to carry out a national postal
      survey to investigate specialist services and specialist staffing for older
      people in England in the wake of recent policy developments. Through reflection
      on this experience, the team propose approaches for the development of existing
      research governance processes. The national survey was the first stage of the
      study, which was followed by a detailed investigation of the development of
      specialist service provision for older people in six case study sites across
      England. The national survey aimed to map specialist service provision for older
      people by identifying the range of service models, agency and professional
      involvements, and nature of the case load in statutory services (health and
      social care), independent and voluntary sector organisations. FINDINGS: Of the
      357 NHS organisations approached for approval to carry out the survey within the
      organisation, this was achieved only in 247 organisations over 12 months. Many
      organisations were facilitative of the process; however, protracted and extensive
      approval processes in others led to long delays and redesigning of the research
      that was commissioned by the Department of Health. ORIGINALITY/VALUE: The paper
      is of value in that it highlights processes and practices that hinder research
      and builds on those that work well.

PMID- 17455814
TI  - Nineteenth century handmaids or twenty-first century partners?
AB  - PURPOSE: The purpose of this paper is to consider the processes influencing the
      nature of the relationship between hospital medical and nursing staff.
      DESIGN/METHODOLOGY/APPROACH: Posits the question "how far has this relationship
      come?" since the influential Briggs Report of the 1970s declared that the
      nineteenth-century handmaid model remained a powerful concept. To address whether
      this still holds true, a series of potentially influencing factors are explored.
      These include the differing historical development of medicine and nursing. Also
      how the relative roles, of nursing in particular, are changing and the effects of
      the external policy and political influences at play. Gender issues are
      considered, with particular regard to how care is conceptualised, and not least
      the contribution to relations by doctors and nurses themselves are explored.
      FINDINGS: The paper discusses how three doctor-nurse relationship models have
      attempted to account for the way these two groups interact. A fourth perspective
      is put forward as a potentially revealing way of viewing group relations, taking
      from the social psychology-based theory of social identification.
      ORIGINALITY/VALUE: The paper maintains that a frank and open discussion of the
      problems that may be encountered in developing the doctor-nurse relationship is a
      vitally important ingredient for modern health care. By employing a polemic style
      the key aim of this paper is to stimulate debate between the relevant parties in
      this area and to attempt to highlight some of the less obvious factors that may
      represent tangible barriers to effective partnership.

PMID- 17455815
TI  - Hostility in coronary artery disease patients and health care workers in
      Slovakia.
AB  - PURPOSE: Increased levels of hostility are associated with the increased risk of
      coronary artery disease (CAD), and with poorer outcomes in CAD patients. The
      purpose of this paper is to estimate the level of hostility in CAD patients and
      in health care (HC) workers, as potential groups for intervention programmes.
      DESIGN/METHODOLOGY/APPROACH: A qualitative cross-sectional study was undertaken.
      Hostility questionnaires were distributed in a non-randomized fashion in a group
      of 236 CAD patients (187 men, 49 women), aged from 33 to 69 years (average 52
      years) and 181 health care workers (52 men, 129 women), aged from 19 to 65
      (average 31 years). The results of the survey were discussed in a focused group.
      FINDINGS: The results showed that the high level of hostility in both CAD
      patients and HC workers exceeded the risk value of 10 in 89 per cent of CAD
      patients and 95 per cent of HC workers. No difference was found in the hostility
      scores between CAD patients and HC workers. There was a tendency to higher scores
      of hostility or of its subcategories (cynicism, anger, aggression) in physicians
      and nurses of the invasive cardiology or the intensive care units.
      ORIGINALITY/VALUE: This paper is of value by showing how increased level of
      hostility was the issue in both patients and HC workers, with potential
      consequences of health risk for individuals, as well as deteriorated
      interpersonal relations and a conflict-generated corporate culture for
      organizations. Differently tailored programmes for hostility management for
      particular target groups may help to prevent negative developments.

PMID- 17455816
TI  - Perfluorooctane sulfonate increases the genotoxicity of cyclophosphamide in the
      micronucleus assay with V79 cells. Further proof of alterations in cell membrane
      properties caused by PFOS.
AB  - Perfluorooctane sulfonate (PFOS; C8F17SO3-) is a fully fluorinated organic
      compound which has been manufactured for decades and was used widely in
      industrial and commercial products. The recent toxicological knowledge of PFOS
      mainly concerns mono-substance exposures of PFOS to biological systems, leaving
      the potential interactive effects of PFOS with other compounds as an area where
      understanding is significantly lacking. However, a recent study, reported the
      potential of PFOS to enhance the toxicity of two compounds by increasing cell
      membrane permeability. This is of particular concern since PFOS has been reported
      to be widely distributed in the environment where contaminants are known to occur
      in complex mixtures. In this study, PFOS was evaluated alone and in combination
      with cyclophosphamide (CPP) to investigate whether a presence of PFOS leads to an
      increased genotoxic potential of CPP towards hamster lung V79 cells. Genotoxicity
      was investigated using the micronucleus (MN) assay according to the recent draft
      ISO/DIS 21427-2 method. PFOS alone demonstrated no genotoxicity up to a
      concentration of 12.5 microg/ml. However, PFOS combined with two different
      concentrations of CPP, with metabolic activation, caused a significant increase
      in the number of micronucleated cells compared to treatments with CPP alone.
      These results provide a first indication that PFOS has the potential to enhance
      the genotoxic action of CPP towards V79 cells, suggesting, together with the
      alterations in cell membrane properties shown previously, that genotoxicity of
      complex mixtures may be increased significantly by changes in chemical uptake.
      Together with an earlier study performed by the own working group, it can be
      concluded that PFOS alone is not genotoxic in this bioassay using V79 cells up to
      12.5 microg/ml, but that further investigations are needed to assess the
      potential interaction between PFOS and other substances, in particular regarding
      the impact of membrane alterations on the uptake of toxic substances.

PMID- 17455817
TI  - Natural organic matter differently modulates growth of two closely related coccal
      green algal species.
AB  - BACKGROUND AND AIM: Humic substances (HS) comprise the majority of dead and
      living organic carbon, including organisms. In the environment, they are
      considered to be chemically inert or at least refractory. Recent papers, however,
      show that HS (including natural organic matter-NOM, isolated by reverse osmosis)
      are natural chemicals which interact with aquatic organisms. They are taken up
      and cause a variety of stress defense reactions which are well known from man
      made chemicals. These reactions include chaperon activation, induction and
      modulation of biotrans-formation enzymes, or induction of antioxidant defense
      enzymes. One specific reaction with freshwater plants is the reduction of
      photosynthetic oxygen release. In this contribution, we compare the
      susceptibilities (cell yield) of two closely related coccal green algae,
      Monoraphidium convolutum and M. minutum, towards various NOM isolates. METHODS:
      Cultures of M. convolutum and M. minutum were obtained from the algal collection
      of the Leibniz Institute of Freshwater Ecology and Inland Fisheries, Berlin, and
      from the Culture Collection of Algae, Gottingen, and maintained in a common
      medium. The cultures were non-axenic. The algae were exposed to 5 mg L(-1) DOC of
      each humic material, an environmentally realistic concentration. Cell numbers
      were counted microscopically in Neugebauer cuvettes in 5 replicates on days 1, 4,
      7, 10, 14, and 21. RESULTS AND DISCUSSION: Almost all NOM isolates modulated the
      growth of the algae. Only the NOM of a Norwegian raised peat bog lake did not
      reveal any significant effect with M. convolutuim. In general, the results with
      two algal species are by no means uniform. For instance, Suwannee River NOM
      causes a decrease in cell density with M. minutum, but temporarily stimulates the
      growth of M. convolutum. The opposite applies to Aurevann NOM: Growth increase in
      M. minutum, but a bi-phasic response in M. convolutum. Different responses of
      both Monoraphidium species must be attributed to intrinsic factors of the algae
      rather than only to chemical features of the exposed materials, because the
      exposures were identical with both algal species. The reduction in growth yields
      can be explained as a herbicide-like mode of action that affects the photosystem
      II most prevalently. The growth promoting effect remains somewhat obscure. It may
      be due to (1) an increase in bioavailability of some trace nutrients in the
      presence of HS, (2) the release of some growth promoting substances by microbial
      or photochemical processing of the humic materials, and (3) a hormetic effect
      upon the exposure of HS. Hormesis means stimulation of organisms or metabolic
      activities when exposed to noxes in low concentrations. However, it is still open
      to discussion why the growth promotion only applies to one or the other, but not
      simultaneously to both Monoraphidium species. CONCLUSION: Exposure of the closely
      related coccal green algal species to humic material changes their growth
      characteristics. Since the reactions are not consistent within the two species
      and the various humic materials, it seems that the less sensitive species is
      favored by HS exposure. The environmental relevance, however, is subject to
      future studies.

PMID- 17455818
TI  - Concentration of organochlorine pollutants in surface waters of the central
      European biosphere reserve Krivoklatsko.
AB  - GOAL, SCOPE AND BACKGROUND: The article is focused on dioxin, furan, PCB and
      organochlorine pesticide monitoring in the surface waters of the Central
      European, protected natural reserve Krivoklatsko, under the UNESCO programme Man
      and Biosphere. Persistent compounds are presently transported via different means
      throughout the entire world. This contamination varies significantly between
      sites. This raises the question of what constitutes the naturally occurring
      background levels of POPs in natural, unpolluted areas, but which are close to
      industrialised regions. Information of real background POP contamination can be
      of high value for risk assessment management of those sites evidently polluted
      and for the defining of de-contamination limits. Preserved areas should not be
      seen as isolated regions in which the impacts of human activities and natural
      factors are either unexpected or overlooked. Every ambient region, even those
      protected by a law or other means, are still closely connected to neighbouring
      human developed and impacted areas, and are therefore subject to this
      anthropogenic contamination. These areas adjacent to natural reserves are sources
      of diverse substances, via entry of air, water, soil and/or biota. After an
      extended period of industrial activities, organochlorine pollutants, even those
      emitted in trace concentrations have reached detectable levels. For future
      research and for the assessment of environmental changes, present levels of
      contamination would be of high importance. This work publishes data of the
      contamination with organochlorine pollutants of this natural region, where
      biodiversity and ecological functions are of the highest order. METHODS:
      Semipermeable membrane devices (SPMDs) were utilised as the sampling system.
      SPMDs were deployed in two small creeks and one water reservoir selected in the
      central part of the Krivoklatsko Natural Reserve, where it could be expected that
      any possible contamination by POPs would be lowest. The exposed SPMDs were
      analysed both for chemical contents of POPs and for toxicity properties. The
      chemical analyses of dibenzodioxins, dibenzo-furans, PCBs and OCPs were analysed
      by GC/MS/MS on GCQ or PolarisQ (Thermoquest). Toxicity bioassays were performed
      on the alga Desmodesmus subspicatus, bacteria Vibrio fischeri and crustacean
      Daphnia magna. All toxicity data were expressed as the effective volume Vtox.
      Vtox is a toxicity parameter, the determination of which is independent of SPMD
      deployment time and pre-treatment dilution (unlike, for example, the EC50 of the
      SPMD extract). RESULTS: The following chemical parameters were monitored: (1)
      tetra, penta, hexa and hepta dibenzo-p-dioxins and furans; (2) all those
      detectable from tri- through deca-polychloriated biphenyls (PCBs) and (3) a group
      of organochlorine pesticides: hexachlorobenzene and isomers of
      hexachlorocyclohexane, DDE, DDD and DDT. The concentrations of dioxins and furans
      on the assessed sites varied from under detection levels up to 7 pg.l(-1); PCBs
      were detected in a sum concentration up to 2.8 ng.l(-1); and organochlorine
      pesticides up to 346 pg.l(-1). The responses of bioassays used were very low,
      with the values obtained for Vtox being under 0.03 l/d. DISCUSSION: Toxicity
      testing showed no toxicity responses, demonstrating that the system used is in
      coherence with the ecological status of the assessed sites. Values of Vtox were
      under the critical value--showing no toxicity. The PCA of chemical analysis data
      and toxicity responses resulted in no correlations between these two groups of
      parameters. This demonstrated that the present level of contamination has had no
      direct adverse effects on the biota. CONCLUSIONS: The concentration values of six
      EPA-listed, toxic dioxins and sums of tetra-hepta dioxins; nine EPA toxic
      dibenzofurans and the sums of tetra-hepta bibenzofurans are presented together
      with all tri-deka PCBs and organochlorine pesticides (alfa-, beta-, gama-, delta
      HCH, HCB, opDDE, ppDDE, opDDD, ppDDD, opDDT, ppDDT). These values represent
      possible current regional natural background values of these substances monitored
      within the Central European region, with no recorded adverse effects on the
      freshwater ecosystem (up until the present time). RECOMMENDATIONS AND
      PERSPECTIVES: Assessment of dioxins, furans and other organochlorine compounds
      within natural reserves can be important for the monitoring of human-induced
      impacts on preserved areas. No systematic monitoring of these substances in areas
      not directly affected by industry has generally been realised. There is a paucity
      of data of the presence of any of these substances within natural regions.
      Further monitoring of contamination of both soil and biota by dioxins and furans
      in preserve regions is needed and can be used for future monitoring of man-made
      activities and/or accidents. Semipermeable membrane devices proved to be a very
      good sampling system for the monitoring of trace concentrations of ambient
      organochlorine compounds. Toxicity evaluation using the Vtox concept demonstrated
      that those localities assessed expressed no toxicity.

PMID- 17455819
TI  - PAH metabolites in bile fluids of dab (Limanda limanda) and flounder (Platichthys
      flesus): spatial distribution and seasonal changes.
AB  - BACKGROUND, AIMS AND SCOPE: Polycyclic aromatic hydrocarbons (PAH) are important
      environmental contaminants which may lead to increased levels of neoplastic
      aberrations or tumours in fish liver. Therefore, monitoring of PAH and their
      effects are part of several international environmental programmes. The aim of
      the present field study was to investigate the concentrations of the PAH
      metabolites in fish bile, to elucidate spatial, seasonal and species differences
      as well as to discuss different strategies of normalisation with regard to
      environmental monitoring. MATERIAL METHODS: PAH metabolites were determined in
      the bile fluid of dab (Limanda limanda) and flounder (Platichthys flesus) caught
      in the North Sea and Baltic Sea between 1997 and 2004. After enzymatic
      deconjugation, two metabolites were determined by means of HPLC. The limit of
      detection and the limit of quantification were calculated. The accuracy of the
      method was tested with a standard reference material. Results were referred to
      bile volume as well as to biliverdin. RESULTS: The main metabolite, 1
      hydroxypyrene, was determined in concentrations from < 0.7 to 838 ng/ml in bile
      of dab (Limanda limanda) and flounder (Platichthys flesus) caught between 1997
      and 2004. The values for 1-hydroxyphenanthrene in fish bile were considerably
      lower (<0.4-87 ng/ml). Significant differences in the 1-hydroxypyrene levels were
      found between summer and winter surveys as well as between the sampling sites in
      the data set from 2004 (383 dabs and 62 flounders): Highest levels of PAH
      contamination were found in dab from the German Bight and in flounder from the
      Baltic Sea. DISCUSSION: Spatial differences in 1-hydroxypyrene concentrations
      between North Sea and Baltic Sea were discussed, as well as differences in
      relation to season, sex and species. Three parameters of normalisation (biliary
      protein, biliverdin and bile pigments) were discussed. Biliverdin was identified
      as a suitable parameter for the normalisation of PAH metabolites in field
      samples. CONCLUSIONS: Spatial differences in 1-hydroxypyrene concentrations of
      dab demonstrate the usefulness of PAH metabolites in fish bile as a monitoring
      parameter in marine regions. Significant differences in 1-hydroxypyrene
      concentrations were found between summer and winter sampling campaigns. This may
      be linked to an annual cycle of 1-hydroxyprene in dab. It is also possible that
      bile synthesis/release in dab differs between the seasons. There is no indication
      for a time trend from 1997 to 2004. RECOMMENDATIONS AND PERSPECTIVES: It is
      recommended to relate PAH metabolites in fish bile to biliverdin concentrations.
      Although the concentrations are low in offshore regions and bile volumes are
      small, the method presented here allows one to measure PAH metabolites on an
      individual level which is a crucial prerequisite for meaningful monitoring
      studies.

PMID- 17455820
TI  - Terbuthylazine contamination of the aquifer north of Vicenza (north-east Italy).
AB  - BACKGROUND AND GOAL: Agricultural practices can affect the quality of aquifers
      given that they are often located in cropped areas, so significant amounts of
      pesticides can be found in the water. In particular, triazine herbicides are
      always carefully checked by the official monitoring systems. The goal of this
      study was to find the mean concentration of terbuthylazine in an Italian aquifer
      and to set up a mass balance of this compound. METHODS: Terbuthylazine
      concentrations in the aquifer were measured in various check-wells during 1998
      2004, and the value of censored data were estimated using a Gompertz inverse in
      order to evaluate the overall mean concentration. The total terbuthylazine load
      in the recharge area was calculated on the basis of surveys of cropped land and
      the main weed control techniques applied in the area. Data on aquifer water
      balance were obtained from previous studies. RESULTS AND DISCUSSION: The
      herbicide terbuthylazine applied in the recharge zone can be transported by
      surface water and enter the aquifer. Detected concentrations were always well
      below the EU drinking water limit and the fraction that can reach the groundwater
      under normal cropping practices is small, very likely less than 0.2%.
      RECOMMENDATIONS AND OUTLOOK: The use and application rates of pesticides should
      be strictly regulated in recharge areas. Vegetated buffer strips can mitigate the
      impact of herbicides on surface water through reducing drift and early-spring
      runoff. Attention should also be paid to the fate of the main metabolites from
      soil biochemical processes.

PMID- 17455821
TI  - How plants cope with foreign compounds. Translocation of xenobiotic glutathione
      conjugates in roots of barley (Hordeum vulgare).
AB  - BACKGROUND AND AIM: Numerous herbicides and xenobiotic organic pollutants are
      detoxified in plants to glutathione conjugates. Following this enzyme catalyzed
      reaction, xenobiotic GS-conjugates are thought to be compartmentalized in the
      vacuole of plant cells. In the present study, evidence is presented from
      experiments with roots of barley (Hordeum vulgare cv. Cherie) that part of these
      conjugates will undergo long range transport in plants, rather than be stored in
      the vacuole. To our knowledge, this is the first report about the unidirectional
      long-range transport of xenobiotic conjugates in plants and the exsudation of a
      glutathione conjugate from the root tips. This could mean that plants possess an
      excretion system for unwanted compounds giving them similar advantages as
      animals. METHODS: Barley plants (Hordeum vulgare) were grown in Petri dishes
      soaked with tap water in the greenhouse. Fluorescence Microscopy. Roots of barley
      seedlings were cut under water, and the end at which the pesticides were applied
      was fixed in an aperture with a thin latex foil and transferred into a drop of
      water on a cover slide. The cover slide was fixed in a measuring chamber on the
      stage of an inverse fluorescence microscope (Zeiss Axiovert 100). Monobromo- and
      Monochlorobimane, two model xenobiotics that are conjugated rapidly in plant
      cells with glutathione, hereby forming fluorescent metabolites, were used as
      markers. Their transport in the root could be followed with high time resolution.
      Spectrometric enzyme assay. Glutathione S-transferase (GST) activity was
      determined in the protein extracts following established methods. Aliquots of the
      enzyme extract were incubated with 1-chloro-2,4-dinitrobenzene (CDNB), or
      monochlorobimane. Controls lacking enzyme or GSH were measured. Pitman chamber
      experiments. Ten days old barley plants or detached roots were inserted into
      special incubation chambers, either complete with tips or decapitated, as well as
      10 days old barley plants without root tips. Compartment A was filled with a
      transport medium and GSH conjugate or L-cysteine conjugate. Compartments B and C
      contained sugar free media. Samples were taken from the root tip containing
      compartment C and the amount of conjugate transported was determined spectro
      photometrically. Results. The transport in roots is unidirectional towards the
      root tips and leads to exsudation of the conjugates at rates between 20 and 200
      nmol min(-1). The microscopic studies have been complemented by transport studies
      in small root chambers and spectroscopic quantification of dinitrobenzene
      conjugates. The latter experiments confirm the microscopic studies. Furthermore
      it was shown that glutathione conjugates are transported at higher rates than
      cysteine conjugates, despite of their higher molecular weights. This observation
      points to the existence of glutathione specific carriers and a specific role of
      glutathione in the root. DISCUSSION: It can be assumed that long distance
      transport of glutathione conjugates within the plant proceeds like GSH or amino
      acid transport in both, phloem and xylem. The high velocity of this translocation
      of the GS-X is indicative of an active transport. For free glutathione, a rapid
      transport-system is essential because an accumulation of GSH in the root tip
      inhibits further uptake of sulfur. Taking into account that all described MRP
      transporters and also the GSH plasmalemma ATPases have side activities for
      glutathione derivatives and conjugates, co-transport of these xenobiotic
      metabolites seems credible. On the other hand, when GS-B was applied to the root
      tips from the outside, no significant uptake was observed. Thus it can be
      concluded that only those conjugates can be transported in the xylem which are
      formed inside the root apex. Having left the root once, there seems to be no
      return into the root vessels, probably because of a lack of inward directed
      transporters. CONCLUSIONS: Plants seem to possess the capability to store
      glutathione conjugates in the vacuole, but under certain conditions, these
      metabolites might also undergo long range transport, predominantly into the plant
      root. The transport seems dependent on specific carriers and is unidirectional,
      this means that xenobiotic conjugates from the rhizosphere are not taken up
      again. The exudation of xenobiotic metabolites offers an opportunity to avoid the
      accumulation of such compounds in the plant. RECOMMENDATIONS AND PERSPECTIVES:
      The role of glutathione and glutathione related metabolites in the rhizosphere
      has not been studied in any detail, and only scattered data are available on
      interactions between the plant root and rhizosphere bacteria that encounter such
      conjugates. The final fate of these compounds in the root zone has also not been
      addressed so far. It will be interesting to study effects of the exsuded
      metabolites on the biology of rhizosphere bacteria and fungi.

PMID- 17455822
TI  - Simulated effects of acidic solutions on element dynamics in monsoon evergreen
      broad-leaved forest at Dinghushan, China. Part 1: dynamics of K, Na, Ca, Mg and
      P.
AB  - BACKGROUND: Acid deposition has become a concern in south China in recent years.
      This phenomenon has increased to a dramatic extent with the large use of cars and
      coal-fueled power plants. As a consequence, soils are becoming acidified and
      their element dynamics will change. A decrease in the nutrient availability will
      lead to slower plant growth and maybe to a change in the forest type with current
      species being replaced by new ones with less nutrient requirements. Because of
      these reasons, it is important to understand how the dynamics of elements will
      change and what mechanism is part of the process. This knowledge is important for
      modeling the acidification process and either finding ways to counter it or to
      predict its consequences. The primary purpose of this study was to provide
      information about how the dynamics of K, Na, Ca, Mg and P are affected by acid
      deposition in a typical forest in southern China. METHODS: Experimental soils and
      saplings were collected directly from the monsoon evergreen broad-leaved forest
      in Dinghushan. All saplings were transplanted individually into ceramic pots in
      August 2000 and placed in an open area near their origin site. Pot soils were
      treated weekly from October 2000 to July 2002 with an acidic solution at pH 3.05,
      pH 3.52, pH 4.00 or pH 4.40, or with tap water as a control. The concentrations
      of SO4(2-), NO3-, K+, Na+, Ca2+, Mg2+ and available P and the pH were measured in
      soil and leachate samples taken at different times. The sapling leaves were
      collected and their element concentrations were measured at the end of the
      experiment. RESULTS AND DISCUSSION: Concentrations of soil exchangeable Ca and Mg
      decreased quickly over time, although only Ca showed changes with the acidic
      solution treatment and soil exchangeable K was stable because of soil weathering.
      Leaching of K, Mg and Ca was dependent upon the treatment acidity. Soil available
      P decreased slowly without any correlation with the acidity of the treatment. All
      the NO3- added by the treatment was taken up by the plants, but the SO4(2-) added
      accumulated in the soil. Amongst the plant species, Schima superba was little
      affected by the treatment, the leaf P content was affected in Acmena
      acuminatissima plants and Cryptocarya concinna was the most susceptible species
      to soil acidification, with a marked decrease of, the leaf K, Ca and Mg
      concentrations when the treatment acidity increased. CONCLUSIONS: Simulated acid
      deposition affected the dynamics of K, Ca and Mg in the monsoon evergreen broad
      leaved forest. The dynamics of Ca in the soil and of K, Mg and Ca in the soil
      leachates were affected by the acidic solution treatment. If such a soil
      acidification occurs, Cryptocarya concinna will be amongst the first affected
      species, but Schima superba will be able to sustain a good growth and mineral
      nutrition. RECOMMENDATIONS AND PERSPECTIVES: Acid deposition will lead to
      imbalance the nutrient elements in the evergreen broad-leaved forest because of
      accelerated leaching losses of soil exchangeable Ca and Mg. Measures should be
      developed to slow down soil acidification or nutrient decrease.

PMID- 17455823
TI  - Statistical modelling of CO and NO2 concentrations in the Athens area. Evaluation
      of emission abatement policies.
AB  - GOAL, SCOPE AND BACKGROUND: This paper describes a statistical modelling
      approach, suggested as a policy tool in the Athens area for the assessment of the
      emissions reduction level required to meet the air quality standards for two
      criteria air pollutants. METHODS: More than ten years of hourly CO and NOx-NO2
      concentration data measured by the monitoring network of the Hellenic Ministry
      for the Environment, Physical Planning and Public Works were analyzed and the
      original dataset has been reduced using a data evaluation procedure. RESULTS AND
      DISCUSSION: Seasonal pollutant concentration trends suggested that the reduction
      of CO and NOx concentrations observed in the beginning of the '90s is almost
      entirely attributed to the increase of the catalyst-equipped cars during this
      period. The numerical parameters of an empirical model relating EU standard
      exceedances with mean annual concentrations were defined and the model was
      validated using datasets from years that were not used for the estimation of
      these parameters. This model was used in conjunction with a roll-back equation as
      a policy tool for the assessment of the effect of different CO and NOx emissions
      reduction scenarios on air quality standard compliance for CO and NO2. Results
      predicted with this empirical modelling approach were assessed with monitored
      data averaged over a 3-year period, giving satisfactory results. CONCLUSION: A
      methodology suggested for assessing the effects of different emissions reduction
      scenarios on air quality standard attainment was successfully applied for CO and
      NO2 in the Athens area. RECOMMENDATION AND PERSPECTIVE: The proposed methodology
      can provide a useful tool for the evaluation of policies already in progress as
      well as the development of future policies for emissions reduction in urban areas
      with similar characteristics, aiming at air quality standard compliance on a
      timely manner, Such a methodology could be applied in other urban areas of Greece
      characterized by dense traffic, therefore assisting the development of national
      policies in relation to air pollutants for which standard exceedances occur.

PMID- 17455824
TI  - Standardized analyses of correction of astigmatism: request for further
      clarification.

PMID- 17455825
TI  - LASIK treatment of mixed astigmatism.

PMID- 17455826
TI  - Acrylic multifocal IOLs.

PMID- 17455827
TI  - A 60 kHz IntraLase femtosecond laser creates a smoother LASIK stromal bed surface
      compared to a Zyoptix XP mechanical microkeratome in human donor eyes.
AB  - PURPOSE: To compare the stromal surfaces created by the latest mechanical
      microkeratome and femtosecond, laser technologies. METHODS: Laser in situ
      keratomileusis (LASIK) flaps were created in six fresh human globes unsuitable
      for transplantation. The eyes were placed in one of two groups of three globes
      each. One group had LASIK flaps created with a Zyoptix XP microkeratome using a
      120-microm head and a fresh blade for each eye. Another group had flaps created
      at an attempted 100-microm thickness using the 60 kHz IntraLase femtosecond
      laser. Immediately following flap creation, the stromal beds were prepared for
      scanning electron microscopy (SEM). Qualitative roughness of the SEM images was
      graded by masked observers. Quantitative roughness of the SEM images was assessed
      using computerized software designed for roughness analysis. Mann-Whitney non
      parametric statistical analysis was performed to compare groups. RESULTS: A
      statistically significant difference was noted in bed smoothness as measured by
      qualitative roughness and quantitative roughness scores. The IntraLase samples
      showed smoother stromal beds compared to the Zyoptix group (qualitative roughness
      = 2.0 +/- 0.7 pm vs 3.6 +/- 1.6 pm, P = .03; quantitative roughness = 20238 +/-
      1869 pm vs 26368 +/- 8133 pm, P = .03). CONCLUSIONS: The 60 kHz IntraLase
      femtosecond laser and the Zyoptix XP 120-microm head using a new blade produced
      smooth, good quality, compact stromal beds qualitatively and quantitatively.
      Because the 60 kHz femtosecond laser permits a tight spot/line separation using
      low energy, it creates a smoother corneal stromal bed compared to previous
      femtosecond laser engines.

PMID- 17455828
TI  - Dry eye and corneal sensitivity after high myopic LASIK.
AB  - PURPOSE: To assess subjective symptoms and objective clinical signs of dry eye
      and investigate corneal sensitivity after high myopic LASIK. METHODS: Twenty eyes
      of 20 patients with a mean age of 34 +/- 7.5 years who had undergone high myopic
      LASIK 2 to 5 years previously and 10 eyes of 10 controls with a mean age of 39.8
      +/- 10.4 years were enrolled in the study. Clinical signs of dry eye and
      subjective dry eye symptoms were determined. The corneal sensitivity was assessed
      using non-contact esthesiometer. RESULTS: The preoperative spherical equivalent
      refraction was -11.40 +/- 1.40 diopters (D) (range: -9.10 to -14.00 D) and the
      intended spherical equivalent refraction correction was -10.40 +/- 1.10 D (range:
      -8.30 to -12.50 D). Schirmer's test score was 14.4 +/- 8.9 mm in patients and 9.0
      +/- 4.2 mm in controls (P = .066). The break-up time was 15.9 +/- 11.2 seconds in
      patients and 14.0 +/- 10.0 seconds in controls (P = .505). The mean corneal
      sensitivity was 73.5 +/- 29.6 mL/min in patients and 78.0 +/- 18.7 mL/min in
      controls (P = .666). The majority (55%) of patients still reported dry eye
      symptoms. Ocular surface disease index indicating degree of dry eye symptoms was
      significantly higher in LASIK patients (18.6 +/- 13.4%) compared to controls (7.5
      +/- 5.7%; P = .022). CONCLUSIONS: The majority of patients who received LASIK for
      high myopia reported ongoing dry eye symptoms, although objective clinical signs
      of tear insufficiency and hypoesthesia were not demonstrable. We assume that
      symptoms represent a form of corneal neuropathy rather than dry eye syndrome.

PMID- 17455829
TI  - Laser epithelial keratomileusis for the correction of hyperopia using a 7.0-mm
      optical zone with the Schwind ESIRIS laser.
AB  - PURPOSE: To investigate the efficacy of laser epithelial keratomileusis (LASEK)
      for the correction of hyperopia using a 7.0-mm optical zone and a 9.0-mm total
      ablation zone diameter with the Schwind ESIRIS flying-spot laser. METHODS: Forty
      seven patients (70 eyes) were treated with a mean preoperative spherical
      equivalent refraction of +2.32 diopters (D) (range: 0 to +5.00 D). All eyes
      underwent LASEK using 15% alcohol with a 20-second application. RESULTS: An
      intact epithelial flap was obtained in 66 (94%) eyes. In 70 eyes at 12 months,
      the mean spherical equivalent refraction was +0.09 D (range: -0.75 to +1.00 D)
      with all (100%) eyes within +/- 1.00 D of the intended correction and 60 (86%)
      eyes within +/- 0.50 D. In 40 eyes with 24-month follow-up, the refractive
      correction remained stable after 6 months. Hyperopic cylindrical corrections were
      attempted in 49 eyes (range: +0.25 to +5.00 D) with vector analysis demonstrating
      a mean 102% correction at 12 to 24 months. In 60 non-amblyopic eyes, uncorrected
      visual acuity was > or = 20/20 in 47 (78%) eyes. Thirty-three (47%) eyes gained 1
      to 2 lines of Snellen decimal equivalent best spectacle-corrected visual acuity,
      30 (43%) eyes showed no change, and 7 (10%) eyes lost 1 line. Eight (11%) eyes at
      12 to 24 months had grade +/- 1 of paracentral corneal haze and 57 (81%) had no
      haze. At 12 months (n = 70), the safety index was 1.06 with an efficacy index of
      0.95. Analysis of higher order wavefront aberrations showed no significant
      changes in root-mean-square values post-operatively, except for a significant
      reduction of fourth order spherical aberration (P < .05). CONCLUSIONS: Laser
      epithelial keratomileusis for hyperopia up to +5.00 D using a 7.0-mm optical zone
      with the Schwind ESIRIS laser provides excellent refractive and visual outcomes
      with minimal complications. In eyes followed for 24 months, the refractive
      correction remained stable after 6 months.

PMID- 17455830
TI  - Contrast sensitivity after LASIK, LASEK, and wavefront-guided LASEK with the VISX
      S4 laser.
AB  - PURPOSE: To evaluate the changes in contrast sensitivity and glare after corneal
      refractive surgery for moderate myopia. METHODS: The study comprised 267 eyes of
      149 patients who underwent LASIK, laser epithelial keratomileusis (LASEK), or
      wavefront-guided LASEK with the VISX STAR S4. Contrast sensitivity was measured
      with VCTS 6500 before surgery and at 2 and 6 months postoperatively. Glare was
      evaluated using questionnaires and the ALC glare test at last follow-up. Contrast
      sensitivity at 2 and 6 months was compared with preoperative contrast sensitivity
      in each group. Glare sensitivity in each group was compared to normal controls.
      RESULTS: Contrast sensitivity did not change after LASIK (P > .05). Contrast
      sensitivity of 3 and 6 cycles per degree (cpd) at 2 months increased after LASEK
      (P < .05) and contrast sensitivity of 6, 12, and 18 cpd at 2 months and 3, 6, 12,
      and 18 cpd at 6 months improved in wavefront-guided LASEK (P < .05). Glare test
      and questionnaires did not show any significant difference between the groups.
      CONCLUSIONS: Wavefront-guided LASEK induced significant increases in contrast
      sensitivity of moderate myopes at high spatial frequencies under mesopic
      conditions by 6 months. Glare was not affected by the different refractive
      procedures.

PMID- 17455831
TI  - Ultrasound biomicroscopy for determining visian implantable contact lens length
      in phakic IOL implantation.
AB  - PURPOSE: To assess the efficacy of the ultrasound biomicroscopic (UBM) method in
      estimating the sulcus-to-sulcus horizontal diameter for Visian Implantable
      Contact Lens (ICL, model V4) length determination to obtain optimal ICL vault.
      METHODS: The results of postoperative ICL vaults in 30 eyes of 18 patients were
      retrospectively analyzed. In 17 eyes, ICL length was determined using the
      conventional method, and in 13 eyes, ICL length was determined using the UBM
      method. The UBM method was carried out by measuring the sulcus to limbus distance
      on each side by 50 MHz UBM and adding the white-to-white diameter by caliper or
      Orbscan. The ICL vaults were measured using the UBM method at 1 and 6 months
      postoperatively and the results were compared between the two groups. Ideal ICL
      vault was defined as vault between 250 and 750 microm. The relation between the
      ICL vault, footplate location, and ICL power was also investigated. RESULTS: In
      the UBM method group, ICL vault was within the ideal range in all 13 (100%) eyes
      at 1 and 6 months postoperatively, whereas in the conventional method group, 10
      (58.8%) eyes showed ideal vault at 1 month postoperatively (P = .01) and 9
      (52.9%) eyes showed ideal vault at 6 months postoperatively (P < .01). The ideal
      ICL footplate location was achieved in the ciliary sulcus in 11 (84.6%) eyes of
      the UBM method group and 10 (64.7%) eyes of the conventional method group.
      However, the differences between the two groups were not statistically
      significant. The ICL vault was not significantly affected by the ICL power.
      CONCLUSIONS: Implantable Contact Lens length determined by the UBM method
      achieved significantly more ideal ICL vault than that of the conventional white
      to-white method. The UBM method is superior to the conventional method in terms
      of predicting the sulcus-to-sulcus horizontal diameter for ICL length
      determination.

PMID- 17455832
TI  - Corneal radii and anterior chamber depth measurements using the IOLmaster versus
      the Pentacam.
AB  - PURPOSE: Corneal radii (R1, R2) and anterior chamber depth are important
      parameters for biometry and refractive surgery. This study aimed to investigate
      whether the IOLMaster, a biometric device, and the Pentacam, a rotating
      Scheimpflug camera, provide comparable results. METHODS: In this prospective
      study, corneal radii and anterior chamber depth were analyzed in 82 eyes of 41
      phakic patients (median age 72 years) using the IOLMaster and Pentacam. Normal
      distribution was confirmed using the Kolmogorov-Smirnov test. A paired t test was
      used for statistical analysis. RESULTS: No statistically significant difference
      was noted for R2 using the Pentacam versus the IOLMaster (P = .40). There was a
      small statistical difference of 0.03 mm (P < .01) for R1 (corresponding to 0.08
      diopters [D]). The IOLMaster measured a mean R1 of 7.87 mm and R2 of 7.67 mm. The
      Pentacam measured mean R1 of 7.90 mm and R2 of 7.69 mm. For anterior chamber
      depth values, a small statistically significant difference of 0.05 mm (P < .001)
      was found (corresponding to 0.01 D). Mean anterior chamber depth measured from
      the epithelium was 3.20 mm for the IOLMaster and 3.25 mm for the Pentacam. The
      Bland-Altman plot showed no distorting trends for either variable. CONCLUSIONS:
      Keratometry and anterior chamber depth were comparable for the two devices. If
      the axial length is known, the Pentacam can be used as a biometric device.

PMID- 17455833
TI  - Theoretical comparison of aberration-correcting customized and aspheric
      intraocular lenses.
AB  - PURPOSE: To assess the performance and optical limitations of standard, aspheric,
      and wavefront-customized intraocular lenses (IOLs) using clinically verified
      pseudophakic eye models. METHODS: White light pseudophakic eye models were
      constructed from physical measurements performed on 46 individual cataract
      patients and subsequently verified using the clinically measured contrast
      sensitivity function (CSF) and wavefront aberration of pseudophakic patients
      implanted with two different types of IOLs. These models are then used to design
      IOLs that correct the astigmatism and higher order aberrations of each individual
      eye model's cornea and to investigate how this correction would affect visual
      benefit, subjective tolerance to lens misalignment (tilt, decentration, and
      rotation), and depth of field. RESULTS: Physiological eye models and clinical
      outcomes show similar levels of higher order aberration and contrast improvement.
      Customized correction of ocular wavefront aberrations with an IOL results in
      contrast improvements on the order of 200% over the control and the Tecnis IOLs.
      The customized lenses can be, on average, decentered by as much as 0.8 mm, tilted
      > 10 degrees , and rotated as much as 15 degrees before their polychromatic
      modulation transfer function at 8 cycles/degree is less than that of the Tecnis
      or spherical control lens. Correction of wavefront aberration results in a
      narrower through focus curve but better out of focus performance for +/- 0.50
      diopters. CONCLUSIONS: The use of realistic eye models that include higher order
      aberrations and chromatic aberrations are important when determining the impact
      of new IOL designs. Customized IOLs show the potential to improve visual
      performance.

PMID- 17455834
TI  - Confocal microscopy changes in epithelial and stromal thickness up to 7 years
      after LASIK and photorefractive keratectomy for myopia.
AB  - PURPOSE: To determine the long-term changes in epithelial, stromal, and corneal
      thickness after LASIK and photorefractive keratectomy (PRK). METHODS: In two
      prospective observational case series, 11 patients (16 eyes) received LASIK and
      12 patients (18 eyes) received PRK to correct myopia or myopic astigmatism. None
      of the corneas had retreatment procedures. Corneas were examined using confocal
      microscopy before and at 1 month, and at 1, 2, 3, 5, and 7 years after surgery.
      Central thicknesses were measured from reflected light intensity profiles
      recorded by confocal microscopy. Postoperative epithelial thickness was compared
      to preoperative, and postoperative stromal and corneal thicknesses were compared
      to thickness at 1 month after surgery. RESULTS: In LASIK, epithelial thickness at
      1 month (51 +/- 4 microm, n = 11) was greater than before surgery (41 +/- 4
      microm, n = 16; P < .001) and remained thicker through 7 years (52 +/- 6 microm,
      n = 13; P < .001). Stromal and corneal thickness did not change between 1 month
      and 7 years after LASIK. After PRK, corneal thickness at 1 year (464 +/- 44
      microm, n = 17) was greater than at 1 month (442 +/- 39 microm, n = 15; P = .001)
      and remained thicker at 7 years after PRK (471 +/- 45 microm, n = 17; P > .001).
      CONCLUSIONS: The early increase in central epithelial thickness after myopic
      LASIK persists for at least 7 years and is probably the result of epithelial
      hyperplasia. Central corneal thickness increases during the first year after PRK
      and remains stable thereafter up to 7 years.

PMID- 17455835
TI  - Calculating intraocular lens geometry by real ray tracing.
AB  - PURPOSE: An implementation of real ray tracing based on Snell's law is tested by
      predicting the refraction of pseudophakic eyes and calculating the geometry of
      intraocular lenses (IOLs). METHODS: The refraction of 30 pseudophakic eyes was
      predicted with the measured corneal topography, axial length, and the known IOL
      geometry and compared to the manifest refraction. Intraocular lens calculation
      was performed for 30 normal eyes and 12 eyes that had previous refractive surgery
      for myopia correction and compared to state-of-the-art IOL calculation formulae.
      RESULTS: Mean difference between predicted and manifest refraction for a 2.5-mm
      pupil were sphere 0.11 +/- 0.43 diopters (D), cylinder -0.18 +/- 0.52 D, and axis
      5.13 degrees +/- 30.19 degrees. Pearson's correlation coefficient was sphere r =
      0.92, P < .01; cylinder r = 0.79, P < .01; and axis r = 0.91, P < .01.
      Intraocular lens calculation for the normal group showed that the mean absolute
      error regarding refractive outcome is largest for SRK II (0.49 D); all other
      formulae including ray tracing result in similar values ranging from 0.36 to 0.40
      D. Intraocular lens calculation for the refractive group showed that depending on
      pupil size (3.5 to 2.5 mm), ray tracing delivers values 0.95 to 1.90 D higher
      compared to the average of Holladay 1, SRK/T, Haigis, and Hoffer Q formulae.
      CONCLUSIONS: It has been shown that ray tracing can compete with state-of-the-art
      IOL calculation formulae for normal eyes. For eyes with previous refractive
      surgery, IOL powers obtained by ray tracing are significantly higher than those
      from the other formulae. Thus, a hyperopic shift may be avoided using ray tracing
      even without clinical history.

PMID- 17455836
TI  - Pressure phosphene tonometry versus Goldmann applanation tonometry for measuring
      intraocular pressure before and after LASIK.
AB  - PURPOSE: To compare pressure phosphene tonometry with Goldmann applanation
      tonometry for measuring intraocular pressure (IOP) before and after LASIK.
      METHODS: Forty-three (18 men and 25 women) consecutive healthy patients underwent
      complete pre- and postoperative LASIK ophthalmologic assessments including
      manifest and cycloplegic refraction, keratometry, and central corneal thickness.
      Three repetitive sets of pressure phosphene tonometry and Goldmann applanation
      tonometry measurements were performed the day before and 3 months following
      uneventful LASIK. RESULTS: Mean preoperative spherical equivalent refraction was 
      4.70 +/- 2.50 diopters (D) (range: -1.50 to -12.90 D) and mean preoperative
      keratometry was 43.95 +/- 1.08 D. After LASIK, spherical equivalent refraction
      was +0.23 +/- 0.11 D and mean keratometry was 39.46 +/- 2.28 D. Preoperative
      pressure phosphene tonometry (12.16 +/- 1.58 mmHg) and Goldmann applanation
      tonometry (12.01 +/- 1.55 mmHg) IOP measurements were similar. Postoperative IOP
      was 10.30 +/- 1.16 mmHg with Goldmann applanation tonometry and 12.20 +/- 1.62
      mmHg with pressure phosphene tonometry. The postoperative IOP difference between
      Goldmann applanation tonometry and pressure phosphene tonometry was 0.15 +/- 1.12
      mmHg (P = .41). The mean change in pachymetry after LASIK was 68.73 +/- 73
      microm. The change in Goldmann applanation between preoperative and postoperative
      LASIK values was 1.71 +/- 1.43 mmHg (P < .0001), a change that was strongly
      correlated with changes in corneal thickness (R = 0.75, P < .0001) and
      keratometry (R = 0.72, P < .0001). No such correlations were found with pressure
      phosphene tonometry. CONCLUSIONS: Goldmann applanation tonometry-measured IOP
      decrease after LASIK is strongly correlated with a decrease in central corneal
      thickness and changes in keratometry, whereas pressure phosphene tonometry
      measured IOP is independent of corneal thickness. Pressure phosphene tonometry
      appears to be a more reliable method for recording tonometry in these patients.

PMID- 17455838
TI  - The effect of moxifloxacin and gatifloxacin on long-term visual outcomes
      following photorefractive keratectomy.
AB  - PURPOSE: To compare the effect of gatifloxacin and moxifloxacin on visual
      outcomes after photorefractive keratectomy (PRK). METHODS: Thirty-five PRK
      patients were treated postoperatively with gatifloxacin (Zymar) in one eye and
      moxifloxacin (Vigamox) in the fellow eye. Postoperative regimens were otherwise
      identical. In a previous study (initial phase), we evaluated epithelial healing.
      In this study (second phase), we compared uncorrected visual acuity (UCVA), best
      spectacle-corrected visual acuity (BSCVA), manifest spherical equivalent (MSE),
      and corneal haze at 6 months postoperatively for 32 patients using the Wilcoxon
      signed ranks test. RESULTS: No statistically significant difference was noted
      between eyes treated with Zymar and Vigamox in terms of UCVA, BSCVA, MSE, or
      corneal haze at 6 months postoperatively. Two (6%) Vigamox-treated eyes versus 0
      (0%) Zymar-treated eyes lost one line of BSCVA from preoperative examination.
      Median UCVA and MSE were equivalent for both groups. CONCLUSIONS: At 6 months
      after PRK, there was no significant difference in visual outcomes with either
      antibiotic.

PMID- 17455837
TI  - Prospective evaluation of PermaVision intracorneal implants using in vivo
      confocal microscopy.
AB  - PURPOSE: To report effects of the PermaVision intracorneal lens at the cellular
      level using in vivo confocal microscopy. METHODS: Four eyes implanted with
      intracorneal lenses beneath an IntraLase flap for correction of hyperopia were
      evaluated preoperatively and 1 to 6 months postoperatively. RESULTS: Intracorneal
      lenses were tolerated in three eyes with little or no haze observed clinically
      and good visual results. Minimal keratocyte activation was detected by confocal
      microscopy, and cell density was decreased posterior to the implants. Epithelial
      thinning was observed 1 month after implantation. Thickness stabilized by 6
      months but remained thinner than baseline (33 +/- 2 microm vs 48 +/- 8 microm, P
      < .01). The fourth eye had a complicated course with early flap displacement
      followed by diffuse lamellar keratitis. Confocal microscopy revealed activated
      keratocytes throughout the anterior stroma. The implant was removed, and recovery
      was promising. CONCLUSIONS: Implantation of intracorneal lenses can induce side
      effects of epithelial thinning, keratocyte loss, and keratocyte activation.

PMID- 17455839
TI  - Non-contact confocal microscopy of the tear film in unoperated eyes.
AB  - PURPOSE: The NIDEK ConfoScan4 (CS4) is a digital scanning slit confocal
      microscope. The corneal structure and tear film can be viewed, magnified,
      measured, and photographed at magnifications up to 500x, in vivo, in a
      noninvasive manner. The objective of this study was to evaluate and illustrate
      various conditions related to dry eye using the CS4 confocal microscope with the
      20x noncontact lens. METHODS: The CS4 was used to evaluate the natural tear film
      in 58 eyes of 29 patients with normal examinations, allergic conjunctivitis,
      nonspecific conjunctivitis, and dry eyes. In a subset of this patient population,
      subjective and objective findings were used to classify mild, moderate, and
      severe dry eye disease states. The usefulness of confocal microscopy as an
      objective tool to diagnose and manage different tear film-related ocular disease
      was also evaluated. RESULTS: The differences in tear film composition were
      visible using confocal microscopy. Photographs demonstrate confocal noncontact
      20x microscopy as a diagnostic tool. CONCLUSIONS: Noncontact confocal microscopy
      is a valuable tool in the diagnosis and treatment of dry eye syndrome and other
      ocular states such as allergic and nonspecific conjunctivitis. It provides a
      simple and effective way to observe, classify, and treat the tear film. As
      investigators visualize and learn more, understanding of this structure will
      continue to improve.

PMID- 17455840
TI  - Connecting the dots. Outlining the organizations involved with EHRs and HIE.

PMID- 17455841
TI  - The value of personal health records. A joint position statement for consumers of
      healthcare by the American Health Information Management Association and the
      American Medical Informatics Association.

PMID- 17455842
TI  - Piecing together the PHR.

PMID- 17455843
TI  - PHRs for the masses? Consumers say they are interested in PHRs, but will they use
      them?

PMID- 17455844
TI  - The HIM role in the PHR. Patient-centered care through patient-centered
      information.

PMID- 17455845
TI  - A public life. Developing a consumer information role in HIM.

PMID- 17455846
TI  - Patient-centered design. The potential of user-centered design in personal health
      records.

PMID- 17455847
TI  - Avoiding culture shock. Using behavior change theory to implement quality
      improvement programs.

PMID- 17455848
TI  - Policies and procedures for a legal EHR.

PMID- 17455849
TI  - Connectivity, privacy, and liability. What medical professionals must consider.

PMID- 17455850
TI  - The PHR quandary. Despite the benefits, issues of technology and trust slow
      adoption.

PMID- 17455851
TI  - Ensuring privacy and security in nationwide data exchange.

PMID- 17455852
TI  - PHRs and physician practices.

PMID- 17455853
TI  - Coding sepsis and SIRS.

PMID- 17455854
TI  - Positioning your facility for severity adjusted coding.

PMID- 17455855
TI  - Passing along the PHR lesson.

PMID- 17455856
TI  - Introduction: the importance of timely and complete placental and autopsy
      reports.
AB  - Poor communication, delayed communication, and failure to identify or evaluate
      significant placental lesions are major causes of failure to explain the cause of
      severe injuries in newborns. Families coping with stillbirth or a child with
      cerebral palsy need to have a sense that their bereavement deserves and is
      receiving major attention, and that a determined effort to explain the cause is
      being made and will be presented in a timely fashion. They are coping with long
      lasting and devastating financial and emotional burdens. The obstetrician,
      neonatologist, and pathologist who have accepted the role of physician to these
      patients have a duty to cooperate as fully as they can to make those burdens as
      bearable as possible.

PMID- 17455857
TI  - Infections and other inflammatory conditions.
AB  - The etiology of cerebral palsy and other related perinatal brain injuries is
      poorly understood. Infections of the central nervous system are rare but
      important causes of neurodisability. Recent evidence suggests that infections and
      other inflammatory conditions apparently limited to the placenta are also
      associated with an increased risk of neurologic impairment. A major hypothesis to
      explain this connection is that cytokines, activated inflammatory cells, and
      other mediators of the innate immune response are released into the fetal
      circulation where they can directly or indirectly affect the development or
      integrity of the central nervous system. This review surveys the organisms,
      mediators, and placental lesions that have been associated with perinatal brain
      injury.

PMID- 17455858
TI  - Fetal and maternal vascular lesions.
AB  - Many commonly diagnosed disorders of the placenta relate to maternal and fetal
      blood flow and are thus common in the placentas of infants with adverse perinatal
      outcomes. Severe uteroplacental vascular disease may lead to extensive placental
      infarction and villous changes of reduced uteroplacental blood flow, a
      morphologic feature commonly associated with intrauterine growth restriction and
      fetal demise. Lesser degrees of villous change are seen in many infants with
      premature delivery, term, and multiple births resulting in admission to the
      neonatal intensive care units. Fetal vascular lesions including chorangiosis and
      fetal thrombotic vasculopathy are two processes that appear to be associated with
      increased risk of poor outcome.

PMID- 17455859
TI  - Cord abnormalities, structural lesions, and cord "accidents".
AB  - As the umbilical cord is the lifeline of the fetus, obstruction or disruption of
      blood flow through the umbilical vessels can lead to severe fetal compromise.
      Obstruction is usually mechanical in nature and is associated with compression of
      the umbilical cord and umbilical vessels. Disruption of umbilical or fetal
      vessels is usually traumatic in origin. These conditions have in common a loss of
      blood flow to the fetus and an association with adverse perinatal outcome.

PMID- 17455860
TI  - Medicolegal issues in multiple pregnancy.
AB  - Any discussion of multiple pregnancy figures prominently in the consideration of
      the medicolegal aspects of placental pathology. Multiple gestations are common
      and becoming more so with assisted reproductive techniques, and multiples are
      associated with a disproportionate share of complications that may result in
      disputes over quality of care. Higher rates of intrauterine growth retardation,
      prematurity, stillbirth, morbidity, mortality, cerebral palsy, anomalous
      development, and malformation as compared with singletons are well documented in
      multiple pregnancy and should be anticipated. Monochorionic placentation and
      complications of vascular anastomosis are important factors contributing to poor
      outcome. Other factors, although occurring in all gestations, are relevant
      because they are more common in multiple gestations.

PMID- 17455861
TI  - Clinical syndromes with variable pathologic features.
AB  - Frequently, placentas sent for pathologic examination include a clinical
      diagnosis that does not suggest a specific placental lesion. Pathologists who do
      not have great experience in this field may need some assistance with selecting
      the pertinent placental lesions to look for. This brief outline is included to
      define these conditions and present a list of the specific placental lesions that
      deserve consideration. The placental examination should be directed with the goal
      of identifying or noting and recording specifically the presence or absence of
      the relevant pathologic lesions. The syndromes or conditions considered in this
      context include neonatal encephalopathy, preterm birth, fetal growth restriction,
      maternal diabetes mellitus, thrombophilias, HELLP syndrome, and fetal hydrops.

PMID- 17455862
TI  - The neuropathology of acquired pre- and perinatal brain injuries.
AB  - Acquired pre- and perinatal brain injuries comprise a significant proportion of
      perinatal neuropathology. They are associated with placental abnormalities,
      maternal factors, multiple gestations, and preterm labor, as well as with the
      later development of cerebral palsy and developmental delay. The patterns of
      perinatal brain injury depend on the etiology (often hypoxic-ischemic) and the
      timing relative to the development of the fetal nervous system, since the
      vulnerabilities of gray and white matter differ across postconceptional age and
      by neuroanatomic site. Nevertheless, characteristic features allow determination
      of the approximate age and cause of each pattern of injury in the perinatal
      brain.

PMID- 17455863
TI  - Diabetes and risk of non-Hodgkin lymphoma: a case-control study.
AB  - AIMS AND BACKGROUND: We investigated the relation between diabetes and the risk
      of non-Hodgkin lymphoma, as epidemiological results are controversial and
      diabetes has been related to the risk of several neoplasms. PATIENTS AND METHODS:
      We analyzed the combined dataset of two Italian case-control studies conducted in
      1985-1997 and 1999-2002. Cases were 671 patients, aged <85 years, with incident,
      histologically confirmed non-Hodgkin lymphoma, and controls were 1799 patients
      admitted to hospitals for acute non-neoplastic conditions. Odds ratios were
      estimated using unconditional multiple logistic regression models including terms
      for age, center, sex, residence and educational level. RESULTS: No material
      association between diabetes and non-Hodgkin lymphoma risk was observed, with an
      odds ratio of 1.12 (95% confidence intervals, 0.70-1.77). No association was
      found in relation to age at first diagnosis of diabetes, years since diagnosis,
      or in younger and older subjects at diagnosis of non-Hodgkin lymphoma.
      CONCLUSIONS: The results of the study allow to exclude a strong association
      between diabetes and non-Hodgkin lymphoma, although the small number of cases
      with diabetes leaves open the possibility of a moderate direct relation.

PMID- 17455864
TI  - Risk factors for bladder cancer.
AB  - AIMS AND BACKGROUND: To summarize risk factors for bladder cancer, emphasizing
      the role of recently established associations and to present some ongoing debates
      on the issue. METHODS: A systematic literature search was performed using MEDLINE
      database on bladder cancer risk factors between January 1985 and June 2006 and by
      detailed examination of the references of original articles, reviews and
      monographs retrieved. RESULTS: Cigarette smoking is recognized as the main cause
      of bladder cancer and accounts for about 50% of cases in developed countries. A
      strong link exists between the amount and duration of cigarette smoking. A high
      risk of bladder carcinoma has been observed in workers exposed to some aromatic
      amines. Based on these and other occupational risks, it has been estimated that 5
      10% of bladder carcinomas in industrialized countries were due to exposures of
      occupational origin. Infectious agents have a major influence on bladder cancer
      risks in the areas of the world where Schistosoma haematobium infestation is
      endemic. Other potential risk factors for bladder cancer are other urinary tract
      infections and drinking tap water with chlorination by-products or arsenic.
      Exposure to certain drugs, like cyclophosphamide used in chemotherapy and heavy
      consumption of phenacetin-containing analgesics, has been shown to cause bladder
      cancer in humans. Total fluid intake and high consumption of fruits and
      vegetables are probably associated with a small decrease in risk. CONCLUSIONS:
      Avoidance of tobacco smoking and incriminated occupational exposures, habitual
      intake of fresh fruits and vegetables, and prevention and control of urinary
      tract infections should be recommended for bladder cancer prevention. Further
      studies are required to assess the role of genetic polymorphisms and their
      modifying effect of lifestyle risk factors for bladder cancer occurrence and to
      evaluate the benefit of bladder cancer screening, particularly in those at high
      risk.

PMID- 17455865
TI  - Epidemiology of colorectal cancer in the Umbria region of Italy: prescreening
      period.
AB  - AIMS AND BACKGROUND: The epidemiology of colorectal cancer in Umbria, Italy, was
      evaluated, and data were analyzed in the pre-screening period to better
      understand the etiology of the disease and to develop screening strategies.
      MATERIALS AND METHODS: Incident data were collected by the Umbrian Population
      Cancer Registry and mortality data by the Nominative Regional Mortality Registry
      from 1994 to 2002. The survival rates relative to Italian cancer registries were
      derived from the Italian Associations of Cancer Registries publications. Time
      trends were analyzed by joinpoint regression. The follow-up for survival rates
      referred to December 31, 2005. RESULTS: The trend of colorectal cancer age
      adjusted incidence showed a slight, constant, but non significant increase over
      time. The mortality trend showed a slight, constant, but non-significant
      decrease. Age at diagnosis remained constant in males, whereas in females it
      showed a significant increase of about 1.5 years. In the last period, all
      incidence rates increased with age, but in males they presented a rapid increase
      in the 55-74 age group, levelled and declined up to 84 and after again reached,
      which could be a consequence of opportunistic screening practice, probably
      undergone by males. Mortality in both sexes increased with age, whereas survival
      rates fell. Comparison of survival rates in some Italian cancer registries showed
      that the Umbria region, in the 1994-1996 period, was the zone with the highest
      relative survival; in the 1996-1999 period, the rate stopped, differently from
      other Italian zones. In the last period, the highest survival rates were recorded
      by registries covering zones with active screening programs. CONCLUSIONS: The
      present reduction of mortality in Umbria, as in other Italian areas, is dependent
      on the natural behavior of the disease, which is linked to a birth cohort-related
      effect of stabilization and decrease in exposure to risk factors.

PMID- 17455866
TI  - Malignant mesothelioma of the pleura and other malignancies in the same patient.
AB  - AIMS AND BACKGROUND: The co-existence of mesothelioma, mostly asbestos-related,
      and other primary malignancies has repeatedly been reported. The present study
      evaluated the frequency of such an occurrence. METHODS: In the period October
      1979-June 2002, 215 cases of malignant pleural mesothelioma were diagnosed at the
      Hospital of Monfalcone, Italy. All the cases of the above series, examined at
      necropsy (169), were included in the study. Occupational histories had been
      obtained from the patients or from their relatives by personal or telephone
      interviews. In 132 cases, asbestos bodies were isolated after chemical digestion
      of lung samples. The thoracic cavities were examined for pleural plaques.
      RESULTS: Additional malignancies were observed in 32 cases (18.9%). Multiple
      tumors were synchronous in 22 cases, metachronous in 8 cases, and synchronous and
      metachronous in 2. Four different tumors were found in 2 cases, 3 malignancies
      were detected in 6 patients, and 2 malignancies in the remaining 24. The most
      frequent additional malignancies were prostate adenocarcinoma (7 cases), non
      Hodgkin lymphoma or chronic lymphocytic leukaemia (5 cases), bladder carcinoma (4
      cases), kidney carcinoma (4 cases), large bowel carcinoma (4 cases), and liver
      cell carcinoma (4 cases). All the patients had histories of exposure to asbestos,
      mostly in shipbuilding. Lung asbestos body burdens ranged between 60 and 230,000
      per gram of dried tissue. Pleural plaques were found in 26 cases. CONCLUSIONS: In
      contrast with other series of the literature, in the present cases the co
      existence of mesothelioma and other malignancies appeared as a relatively
      frequent event. The lack of a control group does not allow definite conclusions
      about the meaning of the occurrence. However, the co-existence of certain tumors
      with asbestos-related mesothelioma suggests that mesothelioma and associated
      malignancies might share some etiologic factors (asbestos and others).

PMID- 17455867
TI  - Comprehensive geriatric assessment in elderly cancer patients: an experience in
      an outpatient population.
AB  - AIMS AND BACKGROUND: Cancer is an age-related disease, and the increase in life
      expectancy will lead to a progressive increase of cancer cases in the elderly (>
      or =70 years of age). We have created a group called GONG (Gruppo Oncologico
      Geriatrico) to apply cancer geriatric assessment in elderly cancer patients, in
      order to select which of them are eligible for oncological treatment or
      supportive care only. PATIENTS AND METHODS: We applied this model to evaluate 153
      patients from March 2004 to August 2005. Our model included three categories of
      patients: frail (at least one of the following items: Activities of Daily Living
      scale <80, > or =3 comorbidities unrelated to the tumor according to the Charlson
      Index, performance status < or =60/> or =3 according respectively to Karnofsky
      and the ECOG scale, > or =1 geriatric syndrome); borderline (patients with
      multiple comorbidities not affecting performance status or ability in daily
      activities); non-frail. RESULTS: Applying the aforementioned criteria, we found
      30 borderline, 14 frail and 109 non-frail patients. Statistical analysis showed a
      significant difference in mortality between frail and non-frail patients (P
      <0.05), whereas there was no difference between borderline and non-frail
      patients. CONCLUSIONS: Our model was thus able to identify patients at higher
      risk of death. These results confirm the importance of cancer geriatric
      assessment also for the clinical evaluation of oncological patients. Additional
      randomized studies with a larger number of patients, also in an adjuvant setting,
      should be performed to confirm the effectiveness of this approach.

PMID- 17455868
TI  - Results of a pilot trial of immunotherapy with dendritic cells pulsed with
      autologous tumor lysates in patients with advanced cancer.
AB  - AIMS AND BACKGROUND: The purpose of the study was to test the immunological and
      clinical effects of infusions of dendritic cells pulsed with autologous tumor
      lysate in patients with advanced cancer. PATIENTS AND METHODS: Peripheral blood
      mononuclear cells from 15 patients with metastatic cancer (melanoma in 10, lung
      cancer in 2, renal cell carcinoma in 1, sarcoma in 1, breast cancer in 1) were
      harvested by leukapheresis after mobilization with GM-CSF (5 microg/kg/day s.c.
      for 4 days). Mononuclear cells were separated and cultured in GM-CSF (1000 U/ml)
      and interleukin-4 (1000 U/ml) for 7 days. Phenotype was assessed by 2-color flow
      cytometry and immunocytochemistry. On day 6, dendritic cells were pulsed with 1 g
      of fresh autologous tumor lysate for 24 h and infused intravenously. Interleukin
      2 (6 million IU), interferon a (4 million IU) and GM-CSF (400 microg) were
      injected s.c. daily for 10 days beginning on the day of dendritic cell infusion.
      Treatment was repeated every 21 days for 3 courses. RESULTS: The morphology,
      immunocytochemistry and phenotype of cultured cells was consistent with dendritic
      cells: intense positivity for HLA-DR and CD86, with negativity for markers of
      other lineages, including CD3, CD4, CD8 and CD14. More than 5 x 10(7) dendritic
      cells were injected in all patients. Nine patients developed >5 mm delayed type
      cutaneous hypersensitivity reactions to tumor lysate+/-GM-CSF after the first
      immunization (larger than GM-CSF in all cases). Median delayed type cutaneous
      hypersensitivity to lysate +/- GM-CSF was 3 cm after the third immunization. One
      melanoma patient with skin, liver, lung and bone metastases had a partial
      response lasting 8 months (followed by progression in the brain). Seven patients
      had stable disease for >3 months, and 7 had progression. CONCLUSIONS: Infusion of
      tumor lysate-pulsed dendritic cells induces a strong cell-mediated antitumor
      immune reaction in patients with advanced cancer and has some clinical activity.

PMID- 17455869
TI  - Efficacy of different regimens of adjuvant radiochemotherapy for treatment of
      glioblastoma.
AB  - AIMS AND BACKGROUND: We retrospectively analyzed the impact of different adjuvant
      chemotherapy regimens in a group of patients treated for glioblastoma compared to
      patients receiving only postoperative radiotherapy. MATERIAL AND METHODS: Eighty
      six consecutive patients underwent radiotherapy between January 2000 and December
      2003: 52 patients received radiotherapy alone, 17 patients radiochemotherapy with
      low-dose temozolomide (20 mg/m(2)) + cyclooxygenase-2-inhibitors (200 mg), 6
      patients radiochemotherapy with high-dose temozolomide (50 mg/m2). Eleven
      patients, with unfavorable prognostic factors, were treated with imatinib and
      55/2.5 Gy. RESULTS: The groups treated with high- and low-dose temozolomide
      showed the longest overall survival (median, 21 months and 17 months,
      respectively). Median overall survival was 9 months for radiation alone and 4
      months for the imatinib-treated group. The same positive trend of temozolomide on
      prolonged overall survival was confirmed when only patients submitted to
      maximally radical resection or patients with KPS >70 were considered. Differences
      in progression-free survival were not statistically significant. CONCLUSIONS:
      Patients treated with adjuvant temozolomide either inside or outside of study
      protocols had survival times similar to other reports or randomized studies. The
      absence of a significant influence of temozolomide on progression-free survival
      could depend on the unavoidable drawbacks and biases of retrospective
      investigations or on the definition of relapse used. The unsatisfactory results
      of radiotherapy plus imatinib may have been due to a high prevalence of
      unfavorable prognostic factors in the respective patients. The ongoing controlled
      trial will further define the efficacy of adjuvant/concomitant imatinib.

PMID- 17455870
TI  - Three-dimensional conformal external beam radiotherapy versus the combination of
      external radiotherapy with high-dose rate brachytherapy in localized carcinoma of
      the prostate: comparison of acute toxicity.
AB  - AIMS AND BACKGROUND: Radiotherapy represents one of the basic therapeutic methods
      in treatment of localized carcinoma of the prostate. Optimal irradiation dose is
      the cornerstone of a successful treatment. Along with local control of the
      disease and overall survival of the patient, possible acute and long-term side
      effects need to be monitored very closely. METHODS: A non-randomized prospective
      study comparing the acute genitourinary and gastrointestinal toxicity in patients
      irradiated for localized carcinoma of the prostate. Fifty-seven patients were
      treated with three-dimensional conformal external beam radiotherapy alone, and in
      the second treatment arm a combination of external beam radiotherapy and high
      dose rate brachytherapy was employed in 40 patients. RESULTS: Three-dimensional
      conformal external beam radiotherapy. Acute G1 genitourinary toxicity was
      recorded in 35.1% of patients, G2 in 22.8%, and G2-3 in one patient (1.7%). Acute
      gastrointestinal toxicity was experienced by 54.4% of patients, G1 in 28.1%, G2
      in 17.5%, and G3 in 8.8%. Three-dimensional conformal external beam radiotherapy
      + brachytherapy. Acute G1 genitourinary toxicity was recorded in 37.5% and grade
      2 in 15% of the patients. Only G1 acute gastrointestinal toxicity was recorded in
      40% of the patients. CONCLUSIONS: Acute G1 genitourinary toxicity was experienced
      by a similar percentage of patients in both treatment arms. Acute G2
      genitourinary toxicity was more frequent in the three-dimensional conformal
      radiotherapy arm. Higher acute genitourinary toxicity, G3 or G4, was recorded
      only in one patient per treatment arm. Acute gastrointestinal toxicity was more
      frequent in the three-dimensional conformal radiotherapy arm. Higher acute
      gastrointestinal toxicity, G2 and G3, was only observed in the three-dimensional
      conformal radiotherapy arm. The acute toxicity observed was of a low grade. The
      combination of external beam radiotherapy with brachytherapy resulted in a lower
      incidence of gastrointestinal toxicity than external beam radiotherapy alone.

PMID- 17455871
TI  - Postoperative radiotherapy for synovial sarcoma of the head and neck during
      pregnancy: clinical and technical management and fetal dose estimates.
AB  - AIMS AND BACKGROUND: In vivo and phantom dosimetry is reported to estimate the
      fetal dose and evaluate the effectiveness of a special shielding device to reduce
      fetal exposure in a woman undergoing postoperative radiation therapy for synovial
      oral cavity sarcoma at the 30th week of pregnancy. METHODS: In vivo measurements
      were performed by placing thermoluminescent dosimeters on 3 points for fetal dose
      estimation: uterine fundus, umbilicus and pubis. A Rando anthropomorphic phantom
      was used to simulate radiotherapy. We also performed off-axis dose measurements
      for wedged beams to estimate the dose contribution of this accessory used in the
      treatment. RESULTS: The special shielding device reduced the fetal dose by 70% on
      average, despite the presence of wedges, which increased the dose by a factor of
      about 2.5. Before delivery the patient received 48 Gy, and from the in vivo
      measurements a fetal dose of 8.5, 1.7 and 0.7 cGy was estimated to the uterine
      fundus, umbilicus and pubis, respectively. CONCLUSIONS: Pre-treatment simulation
      in the same irradiation conditions is the only reliable approach to predict the
      fetal dose. By using a special shielding device, radiotherapy can be optimized
      while keeping the fetal exposure below the risk of deterministic damage.

PMID- 17455872
TI  - Preoperative chemoradiation and intra-operative radiotherapy for pancreatic
      carcinoma.
AB  - AIMS AND BACKGROUND: In recent years, preoperative chemoradiation has received
      growing interest for the treatment of locally advanced pancreatic cancer. In an
      attempt to improve resectability and disease control, we used preoperative
      radiation therapy and concomitant 5-fluorouracil in a combined modality therapy
      protocol. The aim of the study was to evaluate definitive results in terms of
      toxicity, response and clinical outcome. MATERIAL AND METHODS: Twenty-eight
      patients with unresectable (cT4, 19 patients) or resectable (cT3, 9 patients)
      nonmetastatic pancreatic tumors received radiotherapy (39.6 Gy) plus 5
      fluorouracil (continuous infusion, days 1-4 at 1000 mg/m(2)/day). After 4 weeks,
      patients were evaluated for surgical resection. In 9 resected patients, electron
      beam intra-operative radiotherapy (10 Gy) was given before reconstruction.
      Thereafter, in resected patients, adjuvant chemotherapy was prescribed. RESULTS:
      During chemoradiation, 1 patient (3.6%) developed grade 3 acute gastrointestinal
      toxicity and 2 patients (7.1%) developed grade 3 hematological toxicity. Three of
      19 patients with unresectable tumors had tumor downstaging (15.8%). Two patients
      showed partial response (response rate, 7.1%; 95% CI, 0.2-25.3) and 4 patients
      (14.3%) had minimal tumor response. Four patients (14.3%) showed progressive
      disease after chemoradiation. One postoperative death was recorded. The median
      survival time was 11.3 months (20.5 and 9.0 months in resected and unresected
      patients, respectively). Only one local failure was recorded in 8 patients
      resected with negative margins. CONCLUSIONS: Although the response rate is still
      low, our preliminary results suggest that preoperative 5-fluorouracil
      chemoradiation is well tolerated and may result in tumor downstaging. Delivery of
      intra-operative radiotherapy seems to be associated with a low rate of local
      recurrences.

PMID- 17455873
TI  - Effect of symptom-to-treatment interval on prognosis in lung cancer.
AB  - AIMS AND BACKGROUND: To evaluate the relationship between delayed diagnosis and
      the degree of invasion and survival in lung cancer. METHODS: One hundred and
      three patients (96 men) with lung cancer were included. Stages in the diagnosis
      of lung cancer were classified as follows: symptom-to-doctor interval, i.e., the
      interval from the first symptoms related to the presence of lung cancer to the
      first consultation with a medical professional; doctor-to-diagnosis interval,
      i.e., the interval between the first medical visit and confirmation of the
      diagnosis; and diagnosis-to-treatment interval, i.e., the interval between
      diagnosis and complete TNM staging and treatment. The symptom-to-treatment
      interval (STI) was the sum of the 3 intervals. The degree of invasion was
      determined by the TNM classification. RESULTS: The patients were followed up for
      a mean period (= SD) of 7.4+/-8.7 months. Seventy-six (74%) patients were
      diagnosed with non-small cell lung cancer (NSCLC) and 27 patients (26%) with
      small cell lung cancer (SCLC). The mean length of STI was 120+/-101 days (median,
      90). The mean length of the symptom-to-doctor interval was 63+/-62 days (median,
      45), while the doctor-to-diagnosis and diagnosis-to-treatment intervals were 41
      +/-82 days (median, 10) and 16+/-12 days (median, 12), respectively. When the
      STIs of the patients were correlated with tumor stage, tumor invasion, lymph node
      involvement and metastasis, no significant differences were found. Patients with
      an STI longer than 60 days had a significantly longer survival. Regarding the
      type of lung cancer and STI, the median survival was shorter in patients with an
      STI of less than 60 days both in NSCLC and SCLC, although this was not
      statistically significant in SCLC. CONCLUSIONS: The shorter the diagnostic
      interval, the shorter was the median survival in our study. The reason for the
      apparent discrepancy between poor prognosis of lung cancer patients in spite of
      early diagnosis might be much faster progression of the disease itself.

PMID- 17455874
TI  - Characteristics of metastasis as a prognostic factor for immunotherapy in
      metastatic renal cell carcinoma.
AB  - AIMS AND BACKGROUND: This study aimed to evaluate the significance of
      characteristics of metastasis as prognostic factors in metastatic renal cell
      carcinoma (RCC). PATIENTS AND METHODS: A total of 148 patients who had received
      immunotherapy were included in the study. Patients were categorized in various
      ways according to the characteristics of metastasis, including a synchronous
      metastasis group (n = 77) vs a metachronous metastasis group (n = 71), and a
      solitary metastasis group (n = 93) vs a multiple metastases group (n = 55).
      RESULTS: In the synchronous and metachronous metastasis groups, median
      progression-free survival was 4.3 months (95% confidence interval [CI] 2.9-5.7)
      and 11.1 months (95% CI 6.7-15.5), respectively (P = 0.004). Median overall
      survival was 17.1 months (95% CI 9.5-24.7) and 54.8 months (95% Cl 38.371.3) in
      the two groups (P = 0.019). In the solitary and multiple metastasis groups,
      median progression-free survival was 11.0 months (95% CI 6.6-15.5) and 3.9 months
      (95% CI 2.6-5.2), respectively (P <0.001). Median overall survival was 55.2
      months (95% CI 50.7-59.7) and 15.6 months (95% CI 10.9-20.3) in the two groups (P
      <0.001). Multivariate Cox proportional hazards model analysis using the clinical
      variables showed that T stage (P = 0.026), number of metastatic sites (P = 0.009)
      and time to metastasis (P = 0.019) were independent predictors of progression
      free survival. Using the same variables, only the number of metastatic sites was
      an independent prognostic predictor of overall survival (P = 0.014). CONCLUSIONS:
      Our findings suggest that the time to metastasis and the number of metastases are
      important prognostic factors in metastatic RCC.

PMID- 17455875
TI  - Anxiety levels in cancer patients and "life sound" experience.
AB  - AIMS AND BACKGROUND: For the hospitalized cancer patient, time takes on a rhythm
      which is very different from the external reality. Based on the idea that time
      represents a fundamental dimension of human existence and is connected to future
      plans, time spent waiting and memories, we carried out this experience entitled
      "Life Sound" project. The objectives of the project were to experiment different
      and unusual ways of spending time in hospital in order to improve the quality of
      life of the hospitalized cancer patient, to help the patient adapt to the
      hospital environment, to encourage awareness of self and to give a different
      meaning to time spent in the hospital. In particular, we evaluated the reduction
      in the levels of anxiety, in psychological suffering and the improvement in
      communication. METHODS: We met with patients, family members, friends, volunteers
      and department personnel (doctors, psychologists, nurses) in a room in the
      Oncology and Hematology Department set aside specifically for recreation
      activities such as having a cup of tea while listening to music, talking, joking,
      listening to people's memories and celebrating birthdays, anniversaries and other
      special days. The study, which involved 109 patients, was carried out through the
      use of the questionnaire STAI-Y distributed before and after the event. RESULTS:
      The results showed a statistically significant difference in anxiety levels 2 hrs
      before participation (mean = 38.33) and 2 hrs after participation (mean = 34.77)
      in the program. This variation was also assessed based on gender, age, cancer
      stage, time since diagnosis and performance status but did not result in any
      statistically significant difference. CONCLUSIONS: The "Life Sound" project
      encourages the emergence of positive feelings, of a renewed willingness to invest
      in personal and caring relationships, which are connected to the patient's
      ability to face this illness, and the opening of new channels of communication
      with family members and hospital staff.

PMID- 17455876
TI  - Is there still a role for the uniscale assessment of quality of life?
AB  - AIMS AND BACKGROUND: To obtain proof of external validity of the visual analogue
      scale and re-evaluate the use of this instrument in assessing cancer patients'
      quality of life. METHODS: Consecutive patients attending 79 Italian medical
      oncology and radiotherapy centers over a period of 1 week were asked to fill out
      both a questionnaire concerning the presence of 19 problems and a 100-mm linear
      visual analogue scale evaluating their quality of life. Quality of life was rated
      as "good" and "bad" when given a score of 70-100 and 0-30, respectively.
      Multifactorial logistic models were used where good and bad quality of life were
      correlated with explanatory variables including patient and disease
      characteristics and the presence or absence of the 19 problems. RESULTS: Gender,
      level of education, treatment setting, Karnofsky performance status, disease
      extent, and the presence of 12 out of 19 problems were found to be correlated
      with good quality of life. A similar pattern of correlations was found with bad
      quality of life. CONCLUSIONS: Due to the difficulties in attaining reliable
      assessment of quality of life using psychometric questionnaires, the further
      proof of validity obtained in this study allows us to propose the re-evaluation
      of the role of the uniscale in measuring the quality of life of cancer patients.

PMID- 17455877
TI  - Skeletal involvement in infants with neuroblastoma a quality control attempt.
AB  - AIMS AND BACKGROUND: In 1994, French authors hypothesized that positive skeletal
      mlBG spots in infants with stage 4 neuroblastoma were not prognostically
      unfavorable unless associated to abnormal standard X-ray or CT findings. In 1999,
      the European Infant Neuroblastoma Study adopted this definition, indeed reducing
      the number of patients candidate to chemotherapy. Such an approach requires high
      quality scans and standardized procedures. The present study critically reviewed
      and assessed the quality of mlBG scans performed in Italian patients enrolled in
      the European Infant Neuroblastoma Study. METHODS: Three independent nuclear
      medicine specialists reviewed scans of 25 Italian patients enrolled in Trials
      99.2, 99.3, and 99.4 of the European Infant Neuroblastoma Study between January
      2000 and September 2002. An arbitrary quality score was attributed to each mlBG
      scintigraphy, ranging from 1 (less than adequate) to 3 (excellent). One
      radiologist and 2 oncologists reviewed the X-rays and CT scans and correlated the
      results with clinical assessment. RESULTS: The quality of mlBG scans was rated
      from good to excellent in 15 of 25 cases, poor in 4, and inadequate for
      diagnostic evaluation in 6. X-rays confirmed the presence of metastases in 3 of 7
      cases with mlBG bone uptake. CT scan confirmed skull metastases in 6 of 9 mlBG
      positive cases. Discrepancies in scan interpretation, making trial and stage
      attribution questionable, were found in 2 patients and are discussed.
      CONCLUSIONS: The quality of mlBG scans proved to be at least acceptable in most
      Italian pediatric oncology centers. Efforts should be made to further standardize
      evaluation of the scans. Additional techniques (99mTc scintigraphy, MRI, SPECT)
      might be useful to help understand the most complex cases.

PMID- 17455878
TI  - Role of computed tomography and [18F] fluorodeoxyglucose positron emission
      tomography image fusion in conformal radiotherapy of non-small cell lung cancer:
      a comparison with standard techniques with and without elective nodal
      irradiation.
AB  - AIMS AND BACKGROUND: Mediastinal elective node irradiation (ENI) in patients with
      non-small cell lung cancer candidate to radical radiotherapy is controversial. In
      this study, the impact of co-registered [18F]fluorodeoxyglucose-positron emission
      tomography (PET) and standard computed tomography (CT) on definition of target
      volumes and toxicity parameters was evaluated, by comparison with standard CT
      based simulation with and without ENI. METHODS: CT-based gross tumor volume
      (GTVCT) was first contoured by a single observer without knowledge of PET
      results. Subsequently, the integrated GTV based on PET/CT coregistered images
      (GTVPET/CT) was defined. Each patient was planned according to three different
      treatment techniques: 1) radiotherapy with ENI using the CT data set alone (ENI
      plan); 2) radiotherapy without ENI using the CT data set alone (no ENI plan); 3)
      radiotherapy without ENI using PET/CT fusion data set (PET plan). Rival plans
      were compared for each patient with respect to dose to the normal tissues (spinal
      cord, healthy lungs, heart and esophagus). RESULTS: The addition of PET-modified
      TNM staging in 10/21 enrolled patients (48%); 3/21 were shifted to palliative
      treatment due to detection of metastatic disease or large tumor not amenable to
      high-dose radiotherapy. In 7/18 (39%) patients treated with radical radiotherapy,
      a significant (> or =25%) change in volume between GTVCT and GTVPET/CT was
      observed. For all the organs at risk, ENI plans had dose values significantly
      greater than no-ENI and PET plans. Comparing no ENI and PET plans, no
      statistically significant difference was observed, except for maximum point dose
      to the spinal cord Dmax, which was significantly lower in PET plans. Notably,
      even in patients in whom PET/CT planning resulted in an increased GTV, toxicity
      parameters were fairly acceptable, and always more favorable than with ENI plans.
      CONCLUSIONS: Our study suggests that [18F]-fluorodeoxyglucose-PET should be
      integrated in no-ENI techniques, as it improves target volume delineation without
      a major increase in predicted toxicity.

PMID- 17455879
TI  - A translocation t(4; 13)(q21;q14) as single clonal chromosomal abnormality in a
      parathyroid adenoma.
AB  - Most of the information about the genetic composition of parathyroid tumors has
      been obtained by comparative genomic hybridization (CGH) and loss of
      heterozygosity (LOH) studies, whereas only few conventional cytogenetic
      investigation results are available. We have performed cytogenetic analysis of
      short-term cultures from 3 parathyroid adenoma tissue samples. Two cases showed a
      normal karyotype in all the metaphases obtained from independent primary
      cultures. In one case 5 metaphases (in a total of 25) from 2 independent cultures
      showed a nonrandom translocation t(4;13)(q21;q14), which was therefore accepted
      as clonal. To our knowledge this is the second clonal translocation described in
      this tumor type. Further conventional cytogenetic analysis of more parathyroid
      tumor specimens would be necessary to identify other specific abnormalities and
      the involved genes with a potential important role in the diagnosis, prognosis
      and pathogenesis of parathyroid tumors.

PMID- 17455880
TI  - Ultrasonography and magnetic resonance imaging findings of solitary fibrous tumor
      of the liver.
AB  - Solitary fibrous tumor of the liver is a rare neoplasm which has been reported in
      only 27 patients in the English literature. A limited number of reports have
      described the radiological findings of this tumor. We report the radiological and
      pathological findings in a patient with solitary fibrous tumor located in the
      liver.

PMID- 17455881
TI  - An adrenal gland nodule presenting as an early sign of metastatic spread from
      colorectal cancer: report of two cases.
AB  - The presence of an adrenal gland nodule may be an early or late sign of
      metastatic spread from colorectal cancer. It usually appears when the internal
      malignancy is widely disseminated and has been previously diagnosed. Adrenal
      insufficiency can be compatible with bilateral and diffuse involvement of this
      uncommon site of disease. Although a surgical approach can be proposed in some
      circumstances, chemotherapy is usually the only therapeutic option. We present 2
      cases that document examples of both events, so as to illustrate the most
      relevant aspects of this condition.

PMID- 17455882
TI  - Perivascular epithelioid cell tumor (PEComa) in the transverse colon of an
      adolescent: a case report.
AB  - Perivascular epithelioid cell tumor (PEComa) is defined as a very rare
      mesenchymal tumor of histologically and immuno-histochemically distinctive
      perivascular epithelioid cells. PEComa in the colon is very rare, with only a few
      reported cases so far. Because of its rarity, the clinical features and
      biological behavior of PEComa in the colon have yet to be established. A 16-year
      old female patient with PEComa in the transverse colon was referred to our
      hospital for rectal bleeding. Laboratory data showed a hemoglobin level of 6.6
      g/dL, WBC of 8,800/mm(3), and platelet count of 191,000/mm(3). Colonoscopy,
      barium enema, and abdominal computed tomography revealed a 2-cm, smooth-surfaced,
      round tumor with focal ulceration in the proximal transverse colon. The patient
      complained of abdominal pain one day after endoscopic polypectomy. She underwent
      a segmental resection for a perforated transverse colon. Immunohistochemically,
      the tumor cells showed strong diffuse positivity for HMB-45 while they were
      negative for c-kit, smooth muscle actin, cytokeratin, S-100, vimentin, desmin,
      chromogranin, synaptophysin, EMA, and CD-34. The diagnosis of PEComa was based on
      histological and immunohistochemical staining. The patient did not receive any
      adjuvant therapy and was discharged on postoperative day 11 without
      complications. Whole-body fluorine-18 fluorodeoxyglucose fusion positron emission
      tomography performed 2 months after surgery showed no signs of recurrence or
      metastasis. There was also no recurrence or metastasis at 24 months' follow-up.

PMID- 17455883
TI  - Simultaneous occurrence of medullary carcinoma and papillary microcarcinoma of
      thyroid in a patient with MEN 2A syndrome. report of a case.
AB  - We report a case of simultaneous multifocal medullary carcinoma and papillary
      microcarcinoma in a patient with several distinctive features of MEN 2A. The
      patient underwent total thyroidectomy and central lymph node dissection. The
      extreme rarity and pathological features of this occurrence are discussed. There
      is no known common cause of these 2 different tumor types; it may be a stochastic
      exception. However, several other possibilities such as a common precursor cell
      or a common tumorigenic stimulus offer interesting perspectives for speculation.

PMID- 17455884
TI  - Brain metastases from endometrial carcinoma: report of three cases and review of
      the literature.
AB  - AIMS AND BACKGROUND: Endometrial carcinoma is a rare cause of brain metastases,
      accounting for less than 1% of all metastatic lesions to the brain. This report
      aims to review our experience in the treatment of patients with brain metastases
      from endometrial carcinoma in order to establish the characteristics of these
      patients and evaluate the results and efficacy of whole-brain radiation therapy
      as a palliative measure. METHODS: Three cases of brain metastases from
      endometrial carcinoma treated with radiotherapy were identified in the files of
      the Division of Radiotherapy at the A. Businco Regional Oncological Hospital of
      Cagliari between 1999 and 2005. RESULTS: All patients had brain metastases as the
      only sign of systemic disease (a single lesion in 2 patients and 2 lesions in 1
      patient). Two patients were classified as RTOG RPA class I and 1 patient as class
      III. Radiotherapy to the brain was delivered after surgical resection in the
      first 2 patients and as the only method of palliation in the third patient. The
      delivered radiation dose was 3000 cGy in 10 fractions over 2 weeks in the
      postoperative setting and 2000 cGy in 5 fractions over 1 week to the patient
      treated with irradiation alone. The 2 surgically treated patients are alive and
      well after 16 and 64 months, respectively. The patient treated with palliative
      intent died 2 months after irradiation. CONCLUSIONS: The combination of surgery
      and postoperative whole-brain irradiation in selected patients with solitary
      brain metastases from endometrial carcinoma is an effective method of palliation.

PMID- 17455885
TI  - Male breast cancer in a young patient treated with nipple-sparing mastectomy:
      case report and review of the literature.
AB  - Male breast carcinoma is an uncommon phenomenon, accounting for less than 1% of
      all malignancies of the breast. The approximate annual incidence in Europe is 1
      in 100,000 cases. The highest incidence occurs 5-10 years later in men than in
      women, with a peak at 60 to 67 years of age. We here describe a case of male
      breast carcinoma in a young patient (44 years of age), which is quite unusual in
      the pattern of breast carcinoma presentation.

PMID- 17455887
TI  - Enhancing cosmetic outcomes by combining superficial glycolic acid (alpha-hydroxy
      acid) peels with nonablative lasers, intense pulsed light, and trichloroacetic
      acid peels.
AB  - Nonablative lasers, intense pulsed light (IPL), and trichloroacetic acid (TCA)
      peels are cosmetic rejuvenation techniques used to remodel skin and provide
      improved skin texture, firmness, and even pigmentation. Glycolic acid is an alpha
      hydroxy acid that can be used as a topical skin peel to provide important
      complementary benefits to nonablative lasers, IPL, and TCA peels. Superficial
      glycolic acid peels provide both epidermal and dermal antiaging benefits, can be
      used to smooth the stratum corneum to reduce light scattering, and can enable the
      use of lower concentrations of TCA during a peel procedure. When used with these
      procedures, glycolic acid peels can enhance skin benefits and perceived patient
      outcomes. Methods of combining nonablative lasers, IPL, and TCA peels with
      glycolic acid peels were discussed at a dermatologist roundtable event and are
      summarized in this article.

PMID- 17455888
TI  - The use of fillers and botulinum toxin type A in combination with superficial
      glycolic acid (alpha-hydroxy acid) peels: optimizing injection therapy with the
      skin-smoothing properties of peels.
AB  - There are many procedures that a physician may utilize to improve the appearance
      and quality of the skin. Combining procedures can enhance the overall result and
      lead to increased patient satisfaction. Thus, it is important to choose
      procedures that will complement each other. Fillers or botulinum toxin type A
      (BTX-A) can plump the skin and smooth lines and wrinkles but will do little for
      uneven tone, skin laxity, or radiance and clarity. These signs of aging can be
      addressed with superficial glycolic acid peels. Methods of combining injectable
      compounds with superficial glycolic acid peels were discussed at a dermatologist
      roundtable event and are summarized in this article.

PMID- 17455889
TI  - Combining superficial glycolic acid (alpha-hydroxy acid) peels with
      microdermabrasion to maximize treatment results and patient satisfaction.
AB  - Microdermabrasion and superficial glycolic acid peels are common aesthetic
      procedures. Microdermabrasion alone provides the benefits of exfoliation but may
      provide faster results and increased patient satisfaction when combined with
      superficial glycolic acid (alpha-hydroxy acid) peels because of the significant
      antiaging effects of glycolic acid peels. A roundtable discussion was held with
      dermatologists to review methods of combining these procedures. The first method
      included alternating glycolic acid peels and microdermabrasion treatments every 2
      weeks, enabling the patient to receive both a peel and microdermabrasion in the
      same month. With the second method, microdermabrasion may be used prior to the
      superficial glycolic acid peel to increase the exfoliation and antiaging effects
      of both treatments within the same visit. This second method is considered to be
      a more aggressive approach and usually is reserved for patients with a history of
      procedures. Lastly, combining treatments can be used to maintain a patient's skin
      after the initial treatment stage, usually performed every other month or
      seasonally, depending on the patient. As with all combination treatments, safety
      precautions and monitoring the patient's skin throughout treatment are crucial to
      success.

PMID- 17455890
TI  - A higher degree of difficulty.

PMID- 17455895
TI  - Exploring the intermembrane space.
AB  - Despite the importance that many components of the intermembrane space (IMS) of
      mitochondria play in cellular function, the targeting sequences that are
      responsible for transporting proteins to this subcellular compartment are not
      fully understood. A recent study has identified a minimized protein sequence that
      is sufficient for localizing the apoptogenic protein Smac/DIABLO in the IMS. This
      newly identified targeting sequence is capable of directing other proteins to
      this submitochondrial compartment as well.

PMID- 17455896
TI  - ADAR editing wobbles the microRNA world.
AB  - Recent work reveals that adenosine-to-inosine editing occurs in a number of
      cellular microRNAs (miRNAs). Such editing is shown to diminish the expression of
      one miRNA and alter the target specificity of another. This changes our current
      views significantly by not only increasing the repertoire of miRNAs and their
      potential targets, but also providing mechanisms for how to regulate them and
      direct them to alternative targets.

PMID- 17455897
TI  - Decoupling the coupling: surface attachment in actin-based motility.
AB  - Actin filament polymerization provides the driving force for several kinds of
      actin-based motility, propelling loads such as the plasma membrane at the leading
      edge of a crawling cell, an endosomal vesicle, or an intracellular bacterial
      pathogen. In these systems, branched filament networks continuously grow while
      simultaneously remaining attached to the load. Previous experiments have
      suggested an important role in both actin filament nucleation and filament
      attachment for a family of proteins called nucleation-promoting factors (NPFs)
      that stimulate actin branch formation and nucleation by the Arp2/3 complex. A
      recent report demonstrates that N-WASP, an NPF, uses distinct domains to mediate
      nucleation and attachment during motility. The surprising details of the
      biochemical mechanism necessitate reconsideration of the biophysical models
      proposed for actin-based motility.

PMID- 17455898
TI  - Mimicking methylated histones.
AB  - Histones with specific patterns of lysine methylation help to define how their
      associated DNA is used. A recent semisynthetic strategy for generating histone
      proteins that contain methyl-lysine analogues at specific sites will provide
      researchers with the materials to further elucidate the role of these
      modifications.

PMID- 17455899
TI  - Self-cutting to kill: new insights into the processing of Clostridium difficile
      toxins.
AB  - Clostridium difficile toxins A and B are the major cause of antibiotic-associated
      diarrhea and pseudomembranous colitis. The toxins are one of the biggest protein
      toxins known, but only the N-terminal catalytic domains of the large proteins
      enter the cytosol. Now, a new study shows that the toxins are processed by
      autocatalytic cleavage, which depends on the presence of inositol hexaphosphate.

PMID- 17455900
TI  - Invertebrate animal models of diseases as screening tools in drug discovery.
AB  - Invertebrate animal models (mainly the nematode Caenorhabditis elegans and the
      fruit fly Drosophila melanogaster) are gaining momentum as screening tools in
      drug discovery. These organisms combine genetic amenability, low cost, and
      culture conditions compatible with large-scale screens. Their main advantage is
      to allow high-throughput screening in a physiological context. On the down side,
      protein divergence between invertebrates and humans causes a high rate of false
      negatives. Despite important limitations, invertebrate models are an imperfect
      yet much needed tool to bridge the gap between traditional in vitro and
      preclinical animal assays.

PMID- 17455901
TI  - Regioselective labeling of antibodies through N-terminal transamination.
AB  - A convenient new method is described for the introduction of ketone groups at the
      N-termini of antibodies. The reaction occurs in the presence of pyridoxal-5'
      phosphate under conditions mild enough to maintain antigen binding function, as
      confirmed by enzyme-linked immunosorbent assay. Further derivatization of these
      functional sites was accomplished through oxime formation, yielding well-defined
      antibody conjugates for a wide range of applications. The ability of the modified
      antibodies to bind their targets was confirmed via immunodot blot analysis. The
      generality of this method has been demonstrated on a number of monoclonal and
      polyclonal antibodies, all with different binding specificities.

PMID- 17455903
TI  - Trends and plot methods in MLR studies.
AB  - Regression toward the mean effects are presented within the field of quantitative
      structure-activity relationship modeling and in situations in which multilinear
      regression techniques are considered for model building. The concept is related
      to the graphical aspect of some scatter plots (experimental vs fitted and fitted
      vs experimental values). These graphs demonstrate how the point cloud is not
      always symmetrically distributed along the so-called "ideal" or "desired" line,
      that is, the bisector of the first and third quadrants. The deviation from the
      ideal line is fixed, and it is also related to the coefficient of determination.
      An extrapolation of these regression effects is also discussed within the context
      of property predictions obtained via the leave-one-out cross-validation
      technique.

PMID- 17455904
TI  - Diversity of new structural types in polynuclear iron chemistry with a tridentate
      N,N,O ligand.
AB  - The syntheses, crystal structures, and magnetochemical characterization of four
      new iron clusters [Fe7O4(O2CPh)11(dmem)2] (1), [Fe7O4(O2CMe)11(dmem)2] (2),
      [Fe6O2(OH)4(O2CBut)8(dmem)2] (3), and [Fe3O(O2CBut)2(N3)3(dmem)2] (4)
      (dmemH=Me2NCH2CH2N(Me)CH2CH2OH)=2-{[2-(dimethylamino)ethyl]methylamino}ethanol)
      are reported. The reaction of dmemH with [Fe3O(O2CR)6(H2O)3](NO3) (R=Ph (1), Me
      (2), and But (3)) gave 1, 2, and 3, respectively, whereas 4 was obtained from the
      reaction of 3 with sodium azide. The complexes all possess rare or novel core
      topologies. The core of 1 comprises two [Fe4(mu3-O)2]8+ butterfly units sharing a
      common body Fe atom. The core of 2 consists of a [Fe3O3] ring with each doubly
      bridging O2- ion becoming mu3 by also bridging to a third, external Fe atom; a
      seventh Fe atom is attached on the outside of this core via an additional mu3-O2-
      ion. The core of 3 consists of a [Fe4(mu3-O)2]8+ butterfly unit with an Fe atom
      attached above and below this by bridging O atoms. Finally, the core of 4 is an
      isosceles triangle bridged by a mu3-O2- ion with a rare T-shaped geometry and
      with the azide groups all bound terminally. Variable-temperature, solid-state dc,
      and ac magnetization studies were carried out on complexes 1-4 in the 5.0-300 K
      range. Fitting of the obtained magnetization (M) vs field (H) and temperature (T)
      data by matrix diagonalization and including only axial anisotropy (zero-field
      splitting) established that 1, 2, and 4 each possess an S=5/2 ground state spin,
      whereas 3 has an S=5 ground state. As is usually the case, good fits of the
      magnetization data could be obtained with both positive and negative D values. To
      obtain more accurate values and to determine the sign of D, high-frequency EPR
      studies were carried out on single crystals of representative complexes 1.4MeCN
      and 3.2MeCN, and these gave D=+0.62 cm-1 and |E|>or=0.067 cm-1 for 1.4MeCN and D=
      0.25 cm-1 for 3.2MeCN. The magnetic susceptibility data for 4 were fit to the
      theoretical chiM vs T expression derived by the use of an isotropic Heisenberg
      spin Hamiltonian and the Van Vleck equation, and this revealed the pairwise
      exchange parameters to be antiferromagnetic with values of Ja=-3.6 cm-1 and Jb=
      45.9 cm-1. The combined results demonstrate the ligating flexibility of dmem and
      its usefulness in the synthesis of a variety of Fex molecular species.

PMID- 17455905
TI  - Flow injection analysis of H2O2 in natural waters using acridinium ester
      chemiluminescence: method development and optimization using a kinetic model.
AB  - Chemiluminescence (CL) of acridinium esters (AE) has found widespread use in
      analytical chemistry. Using the mechanism of the reaction of H2O2 with 10-methyl
      9-(p-formylphenyl)acridinium carboxylate trifluoromethanesulfonate and a modified
      flow injection system, the reaction rates of each step in the mechanism were
      evaluated and used in a kinetic model to optimize the analysis of H2O2.
      Operational parameters for a flow injection analysis system (reagent pH, flow
      rate, sample volume, PMT settings) were optimized using the kinetic model. The
      system is most sensitive to reaction pH due to competition between AE hydrolysis
      and CL. The optimized system was used to determine H2O2 concentrations in natural
      waters, including rain, freshwater, and seawater. The lower limit of detection
      varied in natural waters, from 352 pM in open ocean seawater (mean, 779 pM +/-
      15.0%, RSD) to 58.1 nM in rain (mean, 6,340 nM +/- 0.92%, RSD). The analysis is
      specific for H2O2 and is therefore of potential interest for atmospheric
      chemistry applications where organoperoxides have been reported in the presence
      of H2O2.

PMID- 17455906
TI  - Binding of a second magnesium is required for ATPase activity of RadA from
      Methanococcus voltae.
AB  - RecA-like strand exchange proteins, which include closely related archaeal
      Rad51/RadA and eukaryal Rad51 and DMC1, play a key role in DNA repair by forming
      helical nucleoprotein filaments which promote a hallmark strand exchange reaction
      between homologous DNA substrates. Our recent crystallographic studies on a RadA
      recombinase from Methanococcus voltae (MvRadA) have unexpectedly revealed a
      secondary magnesium at the subunit interface approximately 11 A from the primary
      one coordinated by ATP and the canonical P-loop. The DNA-dependent ATPase
      activity of MvRadA appears to be dependent on the concentration of free Mg2+,
      while the strand exchange activity does not. We also made site-directed
      mutagenesis at the Mg2+-liganding residue Asp-246. The mutant proteins exhibited
      approximately 20-fold reduced ATPase activity but normal strand exchange
      activity. Structurally, the main chain carbonyl of the conserved catalytic
      residue Glu-151 is hydrogen bonded with one of the magnesium-liganding water
      molecules. Changes in the secondary magnesium site may therefore induce
      conformational changes around this catalytic glutamate and affect the ATPase
      activity without significantly altering the stability of the extended recombinase
      filament. Asp-246 is somewhat conserved among archaeal and eukaryal homologues,
      implying some homologues may share this allosteric site for ATPase function.

PMID- 17455907
TI  - Role of the hydrophobic segment of diacylglycerol kinase epsilon.
AB  - Diacylglycerol kinase epsilon (DGKepsilon) is unique among mammalian DGK isoforms
      in having a segment of hydrophobic amino acids. We have evaluated the
      contributions of this segment to the membrane interactions and functions of this
      protein. To test the role of the hydrophobic segment, we have compared the
      properties of DGKepsilon with those of a truncated form of the protein
      (DGKDeltaepsilon) lacking the 40 N-terminal amino acids, which includes the
      hydrophobic segment. The proteins were expressed in COS-7 cells from a gene for
      human DGKepsilon or from a gene for a truncated form (DGKDeltaepsilon), both of
      which had a FLAG tag at the amino terminus. Full-length FLAG-DGKepsilon and
      truncated FLAG-DGKDeltaepsilon were both more specific for 1-stearoyl-2
      arachidonoyl-sn-glycerol than for 1,2-dioleoyl-sn-glycerol. 1-Stearoyl-2
      linoleoyl-sn-glycerol exhibited intermediate specificity for both forms of the
      enzyme. The results show that the truncated form of the enzyme maintains
      substrate specificity for lipids with an arachidonoyl moiety present at the sn-2
      position. The truncation increases the catalytic rate constant for all three
      substrates and may suggest a role in the negative regulation of this enzyme. A
      full-length DGKepsilon with a C-terminal His tag exhibited substrate specificity
      similar to that of the other two forms of the enzyme, indicating that the nature
      and position of the epitope tag did not strongly affect this property. Using an
      ultracentrifugation floatation assay, we showed that at neutral pH
      DGKDeltaepsilon is extracted with 1.5 M KCl while DGKepsilon remains essentially
      fully membrane bound. The full-length protein had a weak tendency to oligomerize
      in the presence of weak detergents. DGKepsilon was monomeric on SDS-PAGE but
      exhibited partial dimerization with low concentrations of perfluorooctanoic acid.
      The major conclusions of this work are that the hydrophobic domain of DGKepsilon
      does not contribute to substrate specificity but plays a role in permanently
      sequestering the enzyme to a membrane.

PMID- 17455908
TI  - Mechanistic investigations of the dehydration reaction of lacticin 481 synthetase
      using site-directed mutagenesis.
AB  - Lantibiotic synthetases catalyze the dehydration of Ser and Thr residues in their
      peptide substrates to dehydroalanine (Dha) and dehydrobutyrine (Dhb),
      respectively, followed by the conjugate addition of Cys residues to the Dha and
      Dhb residues to generate the thioether cross-links lanthionine and
      methyllanthionine, respectively. In this study ten conserved residues were
      mutated in the dehydratase domain of the best characterized family member,
      lacticin 481 synthetase (LctM). Mutation of His244 and Tyr408 did not affect
      dehydration activity with the LctA substrate whereas mutation of Asn247, Glu261,
      and Glu446 considerably slowed down dehydration and resulted in incomplete
      conversion. Mutation of Lys159 slowed down both steps of the net dehydration:
      phosphorylation of Ser/Thr residues and the subsequent phosphate elimination step
      to form the dehydro amino acids. Mutation of Arg399 to Met or Leu resulted in
      mutants that had phosphorylation activity but displayed greatly decreased
      phosphate elimination activity. The Arg399Lys mutant retained both activities,
      however. Similarly, the Thr405Ala mutant phosphorylated the LctA substrate but
      had compromised elimination activity. Finally, mutation of Asp242 or Asp259 to
      Asn led to mutant enzymes that lacked detectable dehydration activity. Whereas
      the Asp242Asn mutant retained phosphate elimination activity, the Asp259Asn
      mutant was not able to eliminate phosphate from a phosphorylated substrate
      peptide. A model is presented that accounts for the observed phenotypes of these
      mutant enzymes.

PMID- 17455909
TI  - Metal ions differentially influence the aggregation and deposition of Alzheimer's
      beta-amyloid on a solid template.
AB  - The abnormal deposition and aggregation of beta-amyloid (Abeta) on brain tissues
      are considered to be one of the characteristic neuropathological features of
      Alzheimer's disease (AD). Environmental conditions such as metal ions, pH, and
      cell membranes are associated with Abeta deposition and plaque formation.
      According to the amyloid cascade hypothesis of AD, the deposition of Abeta42
      oligomers as diffuse plaques in vivo is an important earliest event, leading to
      the formation of fibrillar amyloid plaques by the further accumulation of soluble
      Abeta under certain environmental conditions. In order to characterize the effect
      of metal ions on amyloid deposition and plaque growth on a solid surface, we
      prepared a synthetic template by immobilizing Abeta oligomers onto a N
      hydroxysuccinimide ester-activated solid surface. According to our study using ex
      situ atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT
      IR), and thioflavin T (ThT) fluorescence spectroscopy, Cu2+ and Zn2+ ions
      accelerated both Abeta40 and Abeta42 deposition but resulted only in the
      formation of "amorphous" aggregates. In contrast, Fe3+ induced the deposition of
      "fibrillar" amyloid plaques at neutral pH. Under mildly acidic environments, the
      formation of fibrillar amyloid plaques was not induced by any metal ion tested in
      this work. Using secondary ion mass spectroscopy (SIMS) analysis, we found that
      binding Cu ions to Abeta deposits on a solid template occurred by the possible
      reduction of Cu ions during the interaction of Abeta with Cu2+. Our results may
      provide insights into the role of metal ions on the formation of fibrillar or
      amorphous amyloid plaques in AD.

PMID- 17455910
TI  - Development of indolequinone mechanism-based inhibitors of NAD(P)H:quinone
      oxidoreductase 1 (NQO1): NQO1 inhibition and growth inhibitory activity in human
      pancreatic MIA PaCa-2 cancer cells.
AB  - NAD(P)H:quinone oxidoreductase 1 (NQO1) is currently an emerging target in
      pancreatic cancer. In this report, we describe a series of indolequinones, based
      on 5-methoxy-1,2-dimethyl-3-[(4-nitrophenoxy)methyl]indole-4,7-dione (ES936), and
      evaluate NQO1 inhibition and growth inhibitory activity in the human pancreatic
      MIA PaCa-2 tumor cell line. The indolequinones with 4-nitrophenoxy, 4
      pyridinyloxy, and acetoxy substituents at the (indol-3-yl)methyl position were
      NADH-dependent inhibitors of recombinant human NQO1, indicative of mechanism
      based inhibition. However, those with hydroxy and phenoxy substituents were poor
      inhibitors of NQO1 enzyme activity, due to attenuated elimination of the leaving
      group. The ability of this series of indolequinones to inhibit recombinant human
      NQO1 correlated with NQO1 inhibition in MIA PaCa-2 cells. The examination of
      indolequinone interactions in complex with NQO1 from computational-based
      molecular docking simulations supported the observed biochemical data with
      respect to NQO1 inhibition. The design of both NQO1-inhibitory and noninhibitory
      indolequinone analogues allowed us to test the hypothesis that NQO1 inhibition
      was required for growth inhibitory activity in MIA PaCa-2 cells. ES936 and its 6
      methoxy analogue were potent inhibitors of NQO1 activity and cell proliferation;
      however, the 4-pyridinyloxy and acetoxy compounds were also potent inhibitors of
      NQO1 activity but relatively poor inhibitors of cell proliferation. In addition,
      the phenoxy compounds, which were not inhibitors of NQO1 enzymatic activity,
      demonstrated potent growth inhibition. These data demonstrate that NQO1
      inhibitory activity can be dissociated from growth inhibitory activity and
      suggest additional or alternative targets to NQO1 that are responsible for the
      growth inhibitory activity of this series of indolequinones in human pancreatic
      cancer.

PMID- 17455911
TI  - Biochemical mechanism of hepatitis C virus inhibition by the broad-spectrum
      antiviral arbidol.
AB  - Hepatitis C affects approximately 3% of the world population, yet its current
      treatment options are limited to interferon-ribavirin drug regimens which achieve
      a 50-70% cure rate depending on the hepatitis C virus (HCV) genotype. Besides
      extensive screening for HCV-specific compounds, some well-established medicinal
      drugs have recently demonstrated an anti-HCV effect in HCV replicon cells. One of
      these drugs is arbidol (ARB), a Russian-made broad-spectrum antiviral agent,
      which we have previously shown to inhibit acute and chronic HCV infection. Here
      we show that ARB inhibits the cell entry of HCV pseudoparticles of genotypes 1a,
      1b, and 2a in a dose-dependent fashion. ARB also displayed a dose-dependent
      inhibition of HCV membrane fusion, as assayed by using HCV pseudoparticles
      (HCVpp) and fluorescent liposomes. ARB inhibition of HCVpp fusion was found to be
      more effective on genotype 1a than on genotypes 1b and 2a. In vitro biochemical
      studies revealed association of ARB with membranelike environments such as
      detergents and with lipid membranes. This association was particularly prominent
      at acidic pH which is optimal for HCV-mediated fusion. Our results suggest that
      the affinity of ARB for lipid membranes could account for its anti-HCV actions,
      together with a differential level of interaction with key motifs in HCV
      glycoproteins of different genotypes.

PMID- 17455912
TI  - Tilted, extended, and lying in wait: the membrane-bound topology of residues Lys
      381-Ser-405 of the colicin E1 channel domain.
AB  - The membrane-bound closed state (zero potential) of the helix 3 segment (Lys-381
      Ser-405) of the colicin E1 channel domain was investigated by site-directed
      fluorescence labeling using a bimane probe tethered to a single cysteine residue
      of each mutant protein. A number of fluorescence properties of the tethered
      bimane probe were measured for the soluble channel mutant proteins as well as for
      the membrane-bound proteins. A new method called helical periodicity surface
      analysis was employed to fit the fluorescence data to a harmonic wave function
      using four different statistical methods. The fit of the various data sets to a
      harmonic wave function indicated that the periodicity of helix 3 in the membrane
      bound state is typical for an amphipathic alpha helix (3.7-4.0 residues per turn
      and an angular frequency between 90 and 97 degrees). Notably, upon membrane
      binding, helix 3 elongates from 15 residues (soluble structure) to 20 residues by
      a three- and two-residue extension at the N- and C-termini of the helix,
      respectively. Dual quencher analysis also revealed that helix 3 is appressed to
      the surface of the membrane with its N-terminus more deeply buried within the
      interfacial region of the bilayer than its C-terminus. Finally, contrary to a
      previous report, our data show that helices 3 and 4 remain separate and
      independent helices upon membrane association in the absence of a membrane
      potential.

PMID- 17455913
TI  - Intermediate release by ADP-L-glycero-D-manno-heptose 6-epimerase.
AB  - ADP-l-glycero-d-manno-heptose 6-epimerase (HldD or AGME, formerly RfaD) catalyzes
      the interconversion of ADP-beta-d-glycero-d-manno-heptose (ADP-d,d-Hep) and ADP
      beta-l-glycero-d-manno-heptose (ADP-l,d-Hep). The latter compound provides the
      heptose moiety that is used in lipopolysaccharide biosynthesis by Gram-negative
      bacteria. Several lines of evidence suggest that the enzyme uses a direct
      oxidation/reduction mechanism involving a tightly bound NADP+ cofactor. An
      initial oxidation at C-6'' gives a 6''-keto intermediate, and a subsequent
      reduction on the opposite face of the carbonyl group generates the epimeric
      product. The reorientation required for the nonstereoselective reduction could
      take place within a single active site, or it could involve the release of the
      intermediate and rebinding in an altered conformation. To distinguish between
      these possibilities, two isotopically labeled substrates (ADP-d,d-Hep) were
      prepared that contained 18O and 2H isotopes at C-7'' and C-6'', respectively. A
      crossover experiment was used to determine whether unlabeled or doubly labeled
      products were formed upon epimerization of a mixture of the two singly labeled
      compounds. After an initial epimeric equilibrium was reached, no crossover could
      be detected, indicating that intermediate release is not intrinsic to the overall
      mechanism. After extended incubation, however, scrambling of the labels could be
      detected, indicating that a low background rate of intermediate release does
      occur. To directly detect the release of the intermediate, the labeled compounds
      were independently epimerized in the presence of a ketone-trapping reagent,
      phenylhydrazine. The corresponding phenylhydrazones were identified by mass
      spectrometry, and the absence of any 2H isotope in the adduct obtained from the
      deuterated starting compound confirmed that the oxidation had occurred at C-6''.

PMID- 17455914
TI  - Value of a hydrogen bond in triosephosphate isomerase loop motion.
AB  - The motion of the active site loop (loop 6) in triosephosphate isomerase is
      investigated in solution by TROSY NMR spin-relaxation experiments. The data show
      clear evidence for motion with an exchange rate constant (kex) of 9000 s-1,
      consistent with opening and closing of this loop being partially rate-limiting to
      catalytic throughput. Similar rate constants are observed for residues in both
      the N- and C-terminal regions of loop 6, suggesting motional coupling of the loop
      hinges. Mutation of tyrosine 208 to a phenylalanine (Y208F) eliminates a hydrogen
      bond in the closed loop conformation. NMR experiments with this mutant enzyme
      indicate an increase in the population of the open conformer and concomitant
      increase in the opening rate constant and a decrease in the rate of loop closure.
      The destabilization of the closed conformer by approximately 3 kJ/mol is
      consistent with a similar decrease in affinity of Y208F for ligand. The site
      specific nature of these experiments leads to additional insight into loop 6
      motion and the role of a conserved residue in modulating this motion.

PMID- 17455915
TI  - Oxidative dehalogenation of perhalogenated benzenes by cytochrome P450 compound
      I.
AB  - Resolution of the identity PBE (RI-PBE) and B3LYP density functional theory
      calculations are used to understand the cytochrome P450-catalyzed, Compound I
      mediated oxidation of perchlorobenzenes, perfluorobenzenes, their phenols, and
      mixed chlorofluorobenzenes to form benzoquinones. Addition of Compound I to the
      chlorine-bearing carbon of perchlorobenzenes and perchlorophenols results in an
      apparently barrierless 1,2-shift of the chlorine atom to form
      hexachlorocyclohexadienones and hydroxypentachlorocyclohexadienones,
      respectively. Hexachlorocyclohexadienone has a significant electron affinity, and
      its radical anion expels chloride in a facile manner to give the
      pentachlorophenoxyl radical. Deprotonation of hydroxypentachlorocyclohexadienones
      results in the expulsion of chloride and provides a direct route to the
      production of tetrachloroquinones. Barrier heights for Compound I addition to
      fluorine-bearing carbons of hexafluorobenzene and pentafluorophenol are
      comparable to those computed for oxidation of benzene via an analogous reaction
      path. In contrast to the chlorinated cases, fluorine migration to
      cyclohexadienones occurs with a moderate barrier. Additionally, gas-phase
      elimination of fluoride from the hexafluorocyclohexadienone radical anion and
      deprotonated hydroxypentafluorocyclohexadienone are not facile. Rather,
      consideration of implicit and explicit solvent is required to achieve favorable
      thermochemistry for fluoride elimination and generation of the experimentally
      observed products. Finally, the theoretical approach described herein is
      predictive of the experimentally observed preferential elimination of fluorine
      from chloropentafluorobenzene and 1,3,5-trichloro-2,4,6-trifluorobenzene. These
      studies illustrate the effectiveness of P450 Compound I as an oxidant of
      halogenated aromatic hydrocarbons, which are persistent environmental
      contaminants, and the potential utility of such computational methods for
      predicting P450 metabolism.

PMID- 17455916
TI  - Direct cellular responses to platinum-induced DNA damage.

PMID- 17455917
TI  - Rovibrational spectra of LiH2+, LiHD+ and LiD2+ determined from FCI property
      surfaces.
AB  - Full configuration interaction (FCI) has been used in conjunction with the
      lithium [6s5p3d1f] (Iron, M. A.; et al. Mol. Phys. 2004, 101, 1345) and hydrogen
      aug-cc-pVTZ basis sets to construct an 83-point potential energy surface of the
      1A1 ground state of 7LiH2+. Vibrational and rovibrational wave functions of the
      (6,7)LiH2+, (6,7)LiHD+, and (6,7)LiD2+ ground states were calculated
      variationally using an Eckart-Watson Hamiltonian. For (7)LiD2+, rovibrational
      transition frequencies for K = 0, 1, 2 and J < or = 10 are within ca. 0.1% of
      recent experimental values (Thompson, C. D.; et al. J. Chem. Phys. 2006, 125,
      044310). A 47-point FCI dipole moment surface was embedded in the rovibrational
      Hamiltonian to calculate vibrational and rovibrational radiative properties. At
      296 K, with v < or = 4 and J < or = 4, the 2(02) <-- 3(03) rotational transition
      in the |001> band was found to have the greatest spectral intensity with respect
      to the ground electronic states of (6,7)LiH2+, (6,7)LiHD+, and (6,7)LiD2+. In
      each case, the most intense rovibrational transitions have been assigned
      unequivocally using the J, Ka, Kc assignment scheme.

PMID- 17455918
TI  - Analysis of HO2 and OH formation mechanisms using FM and UV spectroscopy in
      dimethyl ether oxidation.
AB  - Product formation pathways in the photolytically initiated oxidation of CH3OCH3
      have been investigated as a function of temperature (298-600 K) and pressure (20
      90 Torr) through the detection of HO2 and OH using Near-infrared frequency
      modulation spectroscopy, as well as the detection of CH3OCH2O2 using UV
      absorption spectroscopy. The reaction was initiated by pulsed photolysis with a
      mixture of Cl2, O2, and CH3OCH3. The HO2 and OH yield is obtained by comparison
      with an established reference mixture, including CH3OH. The CH3OCH2O2 yield is
      also obtained through the procedure of estimating the CH3OCH2O2/HO2 ratio from
      their UV absorption. A notable finding is that the OH yield is 1 order of
      magnitude larger than those known in C2 and C3 alkanes, increasing from 10% to
      40% with increasing temperature. The HO2 yield increases gradually until 500 K
      and sharply up to 40% over 500 K. The CH3OCH2O2 profile has a prompt rise,
      followed by a gradual decay whose time constant is consistent with slow HO2
      formation. To predict species profiles and yields, simple chlorine-initiated
      oxidation model of DME under low-pressure condition was constructed based on the
      existing model and the new reaction pathways, which were derived from this study.
      To model rapid OH formation, OH direct formation from CH3OCH2 + O2 was required.
      We have also proposed that a new HCO formation pathway via QOOH isomerization to
      HOQO species and OH + CH3OCH2O2 --> HO2 + CH3OCH2O are to be considered, to
      account for the fast and slow HO2 formations, as well as the total yield. The
      constructed model including these new pathways has successfully predicted
      experimental results throughout the entire temperature and pressure ranges
      investigated. It was revealed that the HO2 formation mechanism changes at 500 K,
      i.e., HCO + O2 via HCHO + OH and the above proposed direct HCO formation
      dominates over 500 K, while a series of reactions following CH3OCH2O2 self
      reaction and OH + CH3OCH2O2 reaction mainly contribute below 500 K. The pressure
      dependent rate constant of the CH3OCH2 thermal decomposition reaction has been
      separately measured since it has large negative sensitivity for HO2 formation and
      is essential to eliminate the ambiguity in the CH3OCH2 + O2 mechanism at higher
      temperature.

PMID- 17455919
TI  - Mechanism of heterogeneous reaction of carbonyl sulfide on magnesium oxide.
AB  - Heterogeneous reaction of carbonyl sulfide (OCS) on magnesium oxide (MgO) under
      ambient conditions was investigated by in situ diffuse reflectance infrared
      Fourier transform spectroscopy (DRIFTS), quadrupole mass spectrometer (QMS), and
      density functional theory (DFT) calculations. It reveals that OCS can be
      catalytically hydrolyzed by surface hydroxyl on MgO to produce carbon dioxide
      (CO2) and hydrogen sulfide (H2S), and then H2S can be further catalytically
      oxidized by surface oxygen or gaseous oxygen on MgO to form sulfite (SO3(2-)) and
      sulfate (SO4(2-)). Hydrogen thiocarbonate (HSCO2-) was found to be the crucial
      intermediate. Surface hydrogen sulfide (HS), sulfur dioxide (SO2), and surface
      sulfite (SO3(2-)) were also found to be intermediates for the formation of
      sulfate. Furthermore, the surface hydroxyl contributes not only to the formation
      of HSCO2- but also to HSCO2- decomposition. On the basis of experimental results,
      the heterogeneous reaction mechanism of OCS on MgO was discussed.

PMID- 17455920
TI  - Electron density topological properties are useful to assess the difference
      between hydrogen and dihydrogen complexes.
AB  - B3LYP/6-31++G(d,p) and MP2/6-31++G(d,p) calculations for a series of hydrogen-
      and dihydrogen-bonded systems have been carried out in order to analyze the
      topology of the electron density and the energy densities at the respective
      energy-optimized bond critical points. Even though there are no significant
      differences when these properties are represented as a function of the
      dimerization energy, they can be separated into two well-defined sets if those
      properties are correlated with intermolecular distances. When analyzing the
      dependence of various properties with equilibrium bond lengths, the specific
      trends of dihydrogen bond systems consist of (a) lower electron density at the
      bond critical point, and (b) lower concentration/depletion of that density which
      can be translated in a different behavior for the Laplacian components.
      Furthermore, the sets of molecules form two different plots which allow for a
      valuable classification between hydrogen- and dihydrogen-bonded systems.

PMID- 17455921
TI  - HN2(2A') electronic manifold. I. A global ab initio study of first two states.
AB  - A detailed ab initio multireference configuration interaction calculation with a
      standard aug-cc-pVTZ basis set is reported for the 1(2)A' and 2(2)A' states of
      the title system. The aim is to establish the dissociation scheme of all
      channels, while revealing the 2(2)A'/3(2)A' seam of conical intersections
      consistent with the crossings in the diatomic fragments. An ab initio mapping of
      linear NNH and T-shaped and linear NHN loci of conical intersections is also
      reported, jointly with a discussion of the topological features associated to a
      newly reported 2(2)A'/3(2)A' crossing seam.

PMID- 17455922
TI  - Electron transfer to protonated beta-alanine N-methylamide in the gas phase: an
      experimental and computational study of dissociation energetics and mechanisms.
AB  - Ammonium radicals derived from protonated beta-alanine N-methyl amide (BANMA)
      were generated by femtosecond collisional electron transfer to gas-phase cations
      prepared by chemical ionization and electrospray. Regardless of the mode of
      precursor ion preparation, the radicals underwent complete dissociation on the
      time scale of 5.15 micros. Deuterium isotope labeling and product analysis
      pointed out several competitive and convergent dissociation pathways that were
      not completely resolved by experiment. Ab initio calculations, which were
      extrapolated up to the CCSD(T)/6-311++G(3df,2p) level of theory, provided the
      proton affinity and gas-phase basicity of BANMA as PA = 971 kJ mol-1 and GB = 932
      kJ mol-1 to form the most stable ion structure 1c+ in which the protonated
      ammonium group was internally solvated by hydrogen bonding to the amide carbonyl.
      Ion 1c+ was calculated to have an adiabatic recombination energy of 3.33 eV to
      form ammonium radical 1c*. The potential energy surface for competitive and
      consecutive isomerizations and dissociations of 1c* was investigated at
      correlated levels of theory and used for Rice-Ramsperger-Kassel-Marcus (RRKM)
      calculations. RRKM unimolecular rate constants suggested that dissociations
      starting from the ground electronic state of radical 1c* were dominated by loss
      of an ammonium hydrogen atom. In contrast, dissociations starting from the B
      excited state were predicted to proceed by reversible isomerization to an
      aminoketyl radical (1f*). The latter can in part dissociate by N-Calpha bond
      cleavage leading to the loss of the amide methyl group. This indicates that
      apparently competitive dissociations observed for larger amide and peptide
      radicals, such as backbone cleavages and losses of side-chain groups, may
      originate from different electronic states and proceed on different potential
      energy surfaces.

PMID- 17455923
TI  - Spectroscopic studies of OCS-doped 4He clusters with 9-72 helium atoms:
      observation of broad oscillations in the rotational moment of inertia.
AB  - High-resolution spectra of HeN-OCS clusters with N up to 39 in the microwave
      region and up to 72 in the infrared region were observed with apparatus-limited
      line widths of about 15 kHz and 0.001 cm(-1), respectively. The cold
      (approximately 0.2 K) clusters were produced in pulsed supersonic jet expansions
      of very dilute OCS + He mixtures and probed using a microwave Fourier transform
      spectrometer or a tunable infrared diode laser spectrometer. Consistent analyses
      of the microwave and infrared data yield band origins for the carbonyl stretching
      vibration, together with rotational parameters for the ground and excited
      vibrational states. The rotational constant, B, passes through a minimum at N = 9
      and then rises as the He atoms uncouple from the OCS rotational motion as a
      result of superfluid effects. There are broad unexpected oscillations in B, with
      maxima at N = 24 and 47 and minima at N = 36 and 62. The change in B upon
      vibrational excitation, which is negative for the OCS molecule, converges to
      positive values for N > 15. These results help to bridge the gap between
      individual molecules and bulk matter with atom-by-atom resolution over a
      significant range of cluster sizes.

PMID- 17455924
TI  - On the effect of 1,4-diazabicyclo[2.2.2]octane on the singlet-oxygen dimol
      emission: chemical generation of 1O2)2 in peroxide reactions.
AB  - The acetone-catalyzed decomposition of monoperoxysulfate ions, the molybdate ion
      induced decay of hydrogen peroxide, and the reactions of N-chlorosuccinimide or N
      bromosuccinimide with hydrogen peroxide and of dimethyldioxirane with tertiary
      amines as well as the thermal decomposition of 1,4-dimethylnaphthalene
      endoperoxide lead to the chemiluminescence of singlet-oxygen dimol species (1O2)2
      emitting at 634 and 703 nm. In contrast to the expected enhancement of (1O2)2
      chemiluminescence upon addition of 1,4-diazabicyclo[2.2.2]octane (DABCO) [Deneke,
      C.F.; Krinsky, N. I. J. Am. Chem. Soc. 1976, 98, 3041. Di Mascio, P.; Sies, H. J.
      Am. Chem. Soc. 1989, 111, 2909.], quenching has been observed. Our data show that
      enhancement of singlet-oxygen dimol chemiluminescence is not a general phenomenon
      and, consequently, DABCO is not a reliable chemiluminescent probe for the
      presence of (1O2)2 in chemical and biochemical systems.

PMID- 17455925
TI  - On the effect of 1,4-diazabicyclo[2.2.2]octane on the singlet-oxygen dimol
      emission: photosensitized generation of (1O2)2.
AB  - Time-resolved singlet-oxygen dimol luminescence has been recorded upon laser
      pulsed photosensitization of singlet oxygen by 2-acetonaphthone or 1-H-phenalen-1
      one in perfluorobenzene, perdeuterobenzene, and perdeuteroacetonitrile. It is
      shown that 1,4-diazabicyclo[2.2.2]octane (DABCO) does not enhance radiative
      properties of the dimol species generated by the photosensitization. Instead,
      DABCO strongly reduces the singlet-oxygen dimol luminescence. Rate constants for
      the quenching of the dimol luminescence by DABCO have been determined for the
      three solvents used.

PMID- 17455926
TI  - Gaseous species as reaction tracers in the solvothermal synthesis of the zinc
      oxide terephthalate MOF-5.
AB  - Gaseous species emitted during the zinc oxide/zinc hydroxide 1,4
      benzenedicarboxylate metal organic framework synthesis (MOF-5, MOF-69c) have been
      used to investigate the reaction scheme that leads to the framework creation.
      Changes of the gas-phase composition over time indicate that the decomposition of
      the solvent diethylformamide occurs at least via two competing reaction pathways
      that can be linked to the reaction's overall water and pH management. From
      isotope exchange experiments, we deduce that one of the decomposition pathways
      leads to the removal of water from the reaction mixture, which sets the
      conditions when the synthesis of an oxide-based (MOF-5) instead of an hydroxide
      based MOF (MOF-69c) occurs. A quantitative account of most reactants and
      byproducts before and after the MOF-5/MOF-69c synthesis is presented. From the
      investigation of the reaction intermediates and byproducts, we derive a proposal
      of a basic reaction scheme for the standard synthesis zinc oxide carboxylate
      MOFs.

PMID- 17455927
TI  - Theoretical study of the mechanism for the Markovnikov addition of imidazole to
      vinyl acetate catalyzed by the ionic liquid [bmIm]OH.
AB  - By performing density functional theory calculations, we have studied the
      Markovnikov addition of imidazole to vinyl acetate catalyzed by 1-butyl-3
      methylimidazolium hydroxide, [bmIm]OH, a novel basic ionic liquid. The purpose is
      to show the detailed reaction mechanism, to rationalize the experimental
      observations, and in particular to better understand the role of [bmIm]OH played
      in the reaction as a catalyst. Two different reaction pathways (stepwise and
      concerted) have been characterized and analyzed in detail. It was found that both
      the cation and anion of [bmIm]OH play important roles in the Markovnikov
      addition, which decrease the barrier and increase the selectivity of Markovnikov
      addition. The present results rationalize the early experimental findings well
      and provide a prototype for theoretically understanding the Markovnikov addition
      catalyzed by room-temperature ionic liquids.

PMID- 17455928
TI  - Potent and selective agonists of human melanocortin receptor 5: cyclic analogues
      of alpha-melanocyte-stimulating hormone.
AB  - The physiological role of melanocortin receptor 5 (MC5R) in humans is not clear
      despite its broad presence in various peripheral sites and in the brain, cortex,
      and cerebellum. To differentiate between functions of this receptor and those of
      the other melanocortin receptors (hMC1,3,4R), peptides with improved receptor
      subtype selectivity are needed. The endogenous ligands, melanocortins, and their
      various synthetic analogues are not particularly selective for hMC5R. In this
      study, cyclic peptides derived from MTII, Ac-Nle-cyclo(Asp-His6-D-Phe7-Arg8-Trp
      Lys)-NH2 (a pan-agonist at the melanocortin receptors) were prepared and tested
      in binding and functional assays on CHO cells expressing hMC1b,3-5R. The
      analogues included in their structures sterically constrained hydrophobic amino
      acids in positions 6 (His) and 8 (Arg), and the D-4,4'-biphenyl residue in
      position 7 (D-Phe). Several of the new compounds were selective potent agonists
      at hMC5R. They are exemplified by peptide 29, Ac-Nle-cyclo(Asp-Oic6-D-4,4'-Bip7
      Pip8-Trp-Lys)-NH2 (Oic=octahydroindole-2-COOH; 4,4'-Bip=4,4'-biphenylalanine;
      Pip=pipecolic acid) of IC50=0.95 nM and EC50=0.99 nM at hMC5R and selectivity for
      this receptor with respect to the other melanocortin receptors greater than 5000
      fold.

PMID- 17455929
TI  - A tetrazolyl-substituted subtype-selective AMPA receptor agonist.
AB  - Replacement of the methyl group of the AMPA receptor agonist 2-amino-3-[3-hydroxy
      5-(2-methyl-2H-5-tetrazolyl)-4-isoxazolyl]propionic acid (2-Me-Tet-AMPA) with a
      benzyl group provided the first AMPA receptor agonist, compound 7, capable of
      discriminating GluR2-4 from GluR1 by its more than 10-fold preference for the
      former receptor subtypes. An X-ray crystallographic analysis of this new analogue
      in complex with the GluR2-S1S2J construct shows that accommodation of the benzyl
      group creates a previously unobserved pocket in the receptor, which may explain
      the remarkable pharmacological profile of compound 7.

PMID- 17455930
TI  - Group 12 metal complexes of [26]hexaphyrin(1.1.1.1.1.1).
AB  - Metalation of meso-hexakis(pentafluorophenyl)-substituted
      [26]hexaphyrin(1.1.1.1.1.1) (1) has been explored with group 12 metal ions
      Zn(II), Cd(II), and Hg(II). Zn(II) and Cd(II) ions afforded dinuclear gable
      shaped complexes 2 and 3 in good yields, while Hg(II) ion provided bis-Hg(II) and
      mono-Hg(II) planar complexes (4 and 5) via C-H bond cleavage.

PMID- 17455931
TI  - Properties of Prussian blue materials manifested in molecular complexes:
      observation of cyanide linkage isomerism and spin-crossover behavior in
      pentanuclear cyanide clusters.
AB  - Pentanuclear, cyanide-bridged clusters [M(tmphen)2]3[M'(CN)6]2 (M/M' = Zn/Cr (1),
      Zn/Fe (2), Fe/Fe (3), Fe/Co (4), and Fe/Cr (5); tmphen = 3,4,7,8-tetramethyl-1,10
      phenanthroline) were prepared by combining [M'III(CN)6]3- anions with mononuclear
      complexes of MII ions with two capping tmphen ligands. The clusters consist of a
      trigonal bipyramidal (TBP) core with three MII ions in the equatorial positions
      and two M'III ions in the axial positions. Compounds 1-4 are isostructural and
      crystallize in the monoclinic space group P21/c. Complex 5 crystallizes in the
      enantiomorphic space group P3221. The magnetic properties of compounds 1 and 2
      reflect the contributions of the individual [CrIII(CN)6]3- and [FeIII(CN)6]3-
      ions. The FeII ions in compounds 3 and 4 exhibit a gradual, temperature-induced
      spin transition between high spin (HS) and low spin (LS), as determined by the
      combination of Mossbauer spectroscopy, magnetic measurements, and single-crystal
      X-ray studies. The investigation of compound 5 by these methods and by IR
      spectroscopy indicates that cyanide linkage isomerism occurs during cluster
      formation. The magnetic behavior of 5 is determined by weak ferromagnetic
      coupling between the axial CrIII centers mediated by the equatorial diamagnetic
      FeII ions. Mossbauer spectra collected in the presence of a high applied field
      have allowed, for the first time, the direct experimental observation of
      uncompensated spin density at diamagnetic metal ions that bridge paramagnetic
      metal ions.

PMID- 17455932
TI  - Metal coordination-assisted near-infrared photochromic behavior: a large
      perturbation on absorption wavelength properties of N,N-donor ligands containing
      diarylethene derivatives by coordination to the rhenium(I) metal center.

PMID- 17455933
TI  - Electronic structure of a metal-organic copper spin-1/2 molecule: bis(4-cyano
      2,2,6,6-tetramethyl-3,5-heptanedionato)copper(II).
AB  - The metal-organic molecule bis(4-cyano-2,2,6,6-tetramethyl-3,5
      heptanedionato)copper(II) (Cu(CNdpm)2) (C24H36N2O4Cu, Cu(II)) is a copper spin
      1/2 system with a magnetic moment of 1.05 +/- 0.04 muB/molecule, slightly smaller
      than the 1.215+/-0.02 muB/molecule for the larger size copper spin-1/2 system
      C36H48N4O4Cu.C4H8O (bis(4-cyano-2,2,6,6-tetramethyl-3,5-heptanedionato)copper(II)
      4,4'-bipyridylethene-THF). There is generally good agreement between
      photoemission from vapor-deposited thin films of the C24H36N2O4Cu on Cu(111) and
      Co(111) and model calculations. Although this molecule is expected to have a gap
      between the highest occupied molecular orbital and the lowest unoccupied
      molecular orbital, the molecule remains surprisingly well screened in the
      photoemission final state.

PMID- 17455934
TI  - 2-Aminopurine flipped into the active site of the adenine-specific DNA
      methyltransferase M.TaqI: crystal structures and time-resolved fluorescence.
AB  - We report the crystal structure of the DNA adenine-N6 methyltransferase, M.TaqI,
      complexed with DNA, showing the fluorescent adenine analog, 2-aminopurine,
      flipped out of the DNA helix and occupying virtually the same position in the
      active site as the natural target adenine. Time-resolved fluorescence
      spectroscopy of the crystalline complex faithfully reports this state: base
      flipping is accompanied by the loss of the very short ( approximately 50 ps)
      lifetime component associated with fully base-stacked 2-aminopurine in DNA, and 2
      aminopurine is subject to considerable quenching by pi-stacking interactions with
      Tyr108 in the catalytic motif IV (NPPY). This proves 2-aminopurine to be an
      excellent probe for studying base flipping by M.TaqI and suggests similar
      quenching in the active sites of DNA and RNA adenine-N6 as well as DNA cytosine
      N4 methyltransferases sharing the conserved motif IV. In solution, the same
      distinctive fluorescence response confirms complete destacking from DNA and is
      also observed when the proposed key residue for base flipping by M.TaqI, the
      target base partner thymine, is substituted by an abasic site analog. The
      corresponding cocrystal structure shows 2-aminopurine in the active site of
      M.TaqI, demonstrating that the partner thymine is not essential for base
      flipping. However, in this structure, a shift of the 3' neighbor of the target
      base into the vacancy left after base flipping is observed, apparently
      replicating a stabilizing role of the missing partner thymine. Time-resolved
      fluorescence and acrylamide quenching measurements of M.TaqI complexes in
      solution provide evidence for an alternative binding site for the extra-helical
      target base within M.TaqI and suggest that the partner thymine assists in
      delivering the target base into the active site.

PMID- 17455935
TI  - Inter-DNA electrostatics from explicit solvent molecular dynamics simulations.

PMID- 17455936
TI  - Concise, asymmetric, stereocontrolled total synthesis of stephacidins A, B and
      notoamide B.
AB  - Concise asymmetric total syntheses of the fungal metabolites (-)-stephacidin A,
      (+)-stephacidin B, and (+)-notoamide B are described. Key features of these total
      syntheses include (1) a facile synthesis of (R)-allyl proline methyl ester, (2) a
      revised route toward the pyranoindole ring system, (3) a novel cross-metathesis
      strategy for the introduction of important functional groups, and (4) an SN2'
      cyclization to form the [2.2.2] bridged bicyclic ring system. Furthermore, our
      synthesis has taken advantage of microwave heating to shorten reaction times as
      well as increase yields for the preparation of vital intermediates.

PMID- 17455937
TI  - NMR studies of coupled low- and high-barrier hydrogen bonds in pyridoxal-5'
      phosphate model systems in polar solution.
AB  - The 1H and 15N NMR spectra of several 15N-labeled pyridoxal-5'-phosphate model
      systems have been measured at low temperature in various aprotic and protic
      solvents of different polarity, i.e., dichloromethane-d2, acetonitrile-d3,
      tetrahydrofuran-d8, freon mixture CDF3/CDClF2, and methanol. In particular, the
      15N-labeled 5'-triisopropyl-silyl ether of N-(pyridoxylidene)-tolylamine (1a), N
      (pyridoxylidene)-methylamine (2a), and the Schiff base with 15N-2-methylaspartic
      acid (3a) and their complexes with proton donors such as triphenylmethanol,
      phenol, and carboxylic acids of increasing strength were studied. With the use of
      hydrogen bond correlation techniques, the 1H/15N chemical shift and scalar
      coupling data could be associated with the geometries of the intermolecular
      O1H1N1 (pyridine nitrogen) and the intramolecular O2H2N2 (Schiff base) hydrogen
      bonds. Whereas O1H1N1 is characterized by a series of asymmetric low-barrier
      hydrogen bonds, the proton in O2H2N2 faces a barrier for proton transfer of
      medium height. When the substituent on the Schiff base nitrogen is an aromatic
      ring, the shift of the proton in O1H1N1 from oxygen to nitrogen has little effect
      on the position of the proton in the O2H2N2 hydrogen bond. By contrast, when the
      substituent on the Schiff base nitrogen is a methyl group, a proton shift from O
      to N in O1H1N1 drives the tautomeric equilibrium in O2H2N2 from the neutral O2
      H2...N2 to the zwitterionic O2-...H2-N(2+) form. This coupling is lost in aqueous
      solution where the intramolecular O2H2N2 hydrogen bond is broken by solute
      solvent interactions. However, in methanol, which mimics hydrogen bonds to the
      Schiff base in the enzyme active site, the coupling is preserved. Therefore, the
      reactivity of Schiff base intermediates in pyridoxal-5'-phosphate enzymes can
      likely be tuned to the requirements of the reaction being catalyzed by
      differential protonation of the pyridine nitrogen.

PMID- 17455938
TI  - Ortho arylation of acetanilides via Pd(II)-catalyzed C-H functionalization.

PMID- 17455939
TI  - Total synthesis of archazolid A.

PMID- 17455940
TI  - Application of the intramolecular Yamamoto vinylogous aldol reaction to the
      synthesis of macrolides.
AB  - An intramolecular version of the Yamamoto vinylogous aldol reaction, a method
      that employs the bulky Lewis acid ATPH to control the site of aldolization, is
      described. This macrocyclization process is effective for the construction of 10
      , 12-, and 14-membered macrolides. The yields are high (70-90%), and the reaction
      can proceed with excellent remote stereocontrol (dr > or = 20:1) with chiral
      substrates.

PMID- 17455941
TI  - Spectral dispersion and water solubilization of BODIPY dyes via palladium
      catalyzed C-H functionalization.
AB  - Fluorescent probes 1 and 2 were prepared directly from tetramethyl-BODIPY via
      palladium-mediated C-H functionalization reactions.

PMID- 17455942
TI  - Synthesis of pyroglutamic acid derivatives via double michael reactions of
      alkynones.
AB  - In the presence of substoichiometric quantities of potassium tert-butoxide and an
      additional metal salt, amide-tethered diacids undergo double Michael reactions
      with alkynones to provide highly functionalized pyroglutamic acid derivatives.
      The metal salt was found to play an important role in improving the
      diastereoselectivities of the reactions.

PMID- 17455943
TI  - One-pot synthesis of 7H-dibenzo[b,d]azepin-7-one by heterogeneous flash vacuum
      pyrolysis with MCM-41 catalysts.
AB  - Homogeneous and heterogeneous flash vacuum pyrolysis (fvp) reactions of 2-(1H
      1,2,3-benzotriazol-1-yl)phenylethanone (1) are reported. Heterogeneous reactions
      were carried out with Al-MCM-41 catalysts, mesoporous molecular sieves of the
      type M41S. In both cases, 7H-dibenzo[b,d]azepin-7-one (4) was the major product;
      however, in the catalytic reactions, yields and selectivity were very high. A
      mechanism for this reaction is also discussed.

PMID- 17455944
TI  - Tandem gold(I)-catalyzed cyclization/electrophilic cyclopropanation of vinyl
      allenes.
AB  - We have developed an expedient method for the synthesis of polycyclic compounds
      from propargyl acetates or vinyl allenes involving up to three Au(I)-catalyzed
      elemental steps: 3,3-rearrangement, metalla-Nazarov reaction, and electrophilic
      cyclopropanation. The reaction proceeds under very mild conditions and in short
      times. The mechanism has been studied by DFT computations.

PMID- 17455945
TI  - Luminex-based triplex immunoassay for the simultaneous detection of soy, pea, and
      soluble wheat proteins in milk powder.
AB  - An automated fluorescent microsphere-based flow cytometric triplex immunoassay,
      using the Luminex 100 flow analyzer with MultiAnalyte Profiling (xMAP)
      technology, was developed for the simultaneous detection of proteins from three
      vegetable sources as potential fraudulent adulterants in milk powder. In the
      final triplex inhibition immunoassay, soluble wheat proteins (SWP) and proteins
      from soy and pea were coupled to three different microsphere sets. A mixture of
      these microsphere sets was transferred to a microtiter plate well together with
      the sample and a mixture of three affinity-purified polyclonal antibodies raised
      against the proteins and labeled with a fluorophore (Alexa 532). After incubation
      for 1.5 h at room temperature in the dark, the fluorescence intensities on the
      microspheres were directly measured (no wash procedure) in the Luminex during 10
      s per well (100 microspheres per set). The sensitivities of the three assays for
      plant protein extracts were determined as 0.5-0.6 microg/mL at 50% inhibition.
      For the detection of the vegetable proteins in milk powder, the samples were
      dissolved in buffer (0.1 g in 10 mL) and further diluted (20 times) to create a
      50% inhibition at approximately 0.5% of the vegetable proteins in the total
      protein content of milk powder. With the help of calibration standards, prepared
      under conditions comparable to those for sample materials, the triplex
      immunoassay proved to be quantitative above 0.1%, although concentrations in high
      heated milk powders were underestimated. Due to the xMAP technology, in which 100
      different microsphere sets can be distinguished, this triplex immunoassay can
      easily be extended to detect other possible adulterants.

PMID- 17455946
TI  - Development of sensitive immunoassays for the detection of the glucuronide
      conjugate of 3-phenoxybenzyl alcohol, a putative human urinary biomarker for
      pyrethroid exposure.
AB  - Pyrethroids are widely used in agriculture as insecticides. This study describes
      a sensitive enzyme-linked immunosorbent assay for the detection of the
      glucuronide conjugate of 3-phenoxybenzyl alcohol, a putative pyrethroid
      metabolite that may be used as a biomarker of exposure to pyrethroids. Four
      antisera were elicited against two different immunizing haptens. Antisera were
      characterized in combination with several coating haptens. The lowest IC50 value
      (0.5 ng/mL) was obtained with antiserum 1891 and 3-phenoxybenzoic acid-BSA
      conjugate as the coating antigen. Antiserum 1891 was highly selective for the
      target compound with an overall cross-reactivity of <0.3% to structurally related
      compounds. The assay sensitivity was negligibly affected by pH 4-9. A 5-fold
      improvement in IC50 was observed using a 10-fold concentrated phosphate-fuffered
      saline as the assay buffer. Compared to assays conducted in normal phosphate
      fuffered saline, the maximal absorbance was almost identical. A good correlation
      (r 2 = 0.99 and 0.97 for urine samples A and B, respectively) was observed
      between spiked levels and the levels detected by the immunoassay.

PMID- 17455947
TI  - Measurement of triclosan in water using a magnetic particle enzyme immunoassay.
AB  - A sensitive magnetic particle-based immunoassay to determine triclosan [5-chloro
      2-(2,4-dichlorophenoxy)phenol] in drinking water and wastewater was developed.
      Rabbit antiserum was produced by immunizing the rabbit with 6-[5-chloro-2-(2,4
      dichlorophenoxy)phenoxy]hexanoic acid-keyhole limpet hemocyanin. Horseradish
      peroxidase was conjugated with 4-[3-bromo-4-(2,4-dibromophenoxy)phenoxy]butyric
      acid via N-hydroxysuccinimide (NHS) and 1-ethyl-3-(3
      dimethylaminopropyl)carbodiimide (EDC). The triclosan antibody was coupled to
      magnetic particles via the NHS/EDC reaction. The antibodies were able to
      recognize some structurally related polybrominated biphenyl ethers but did not
      recognize various common pollutants that were less similar to the hapten. The
      ELISA could detect triclosan in standard solution (25% methanol/H2O v/v) at 20
      ppt and its metabolite, methyl-triclosan, at 15 ppt. Water samples from different
      treatment stages were prepared to contain 25% methanol and analyzed directly
      without any sample extraction or preconcentration. The results showed that
      recoveries were >80% and the % CV was <10%, demonstrating the assay was both
      accurate and precise. Application of the triclosan ELISA to water treatment
      plants showed that tap water at various purification stages had low
      concentrations of triclosan (<20 ppt) and required an increased sample size for
      appropriate detection and measurement. Application of ELISA to the wastewater
      treatment plants (WWTP) demonstrated high concentrations of triclosan (in
      general, >3000 ppt in water entering the WWTP) with the levels decreasing as the
      water proceeded through the processing plant (<500 ppt at outflow sewage). The
      ELISA measurement was shown to be equivalent to the more specific GC-MS analysis
      on a number of wastewater treatment samples with a high degree of correlation,
      with the exception of a few samples with very high triclosan concentrations
      (>5000 ppt). Measurement of methyl-triclosan (in WWTP) using GC-MS demonstrated
      the levels of this compound to be low. In summary, a rapid, sensitive, accurate,
      and precise magnetic particle-based immunoassay has been developed for triclosan
      analysis, which can serve as a cost-effective monitoring tool for various water
      samples.

PMID- 17455948
TI  - Environmental analysis by on-line immunoextraction and reversed-phase liquid
      chromatography: optimization of the immunoextraction/RPLC interface.
AB  - The use of antibodies in HPLC columns for on-line immunoextraction combined with
      reversed-phase liquid chromatography (RPLC) is of growing interest in
      environmental and agricultural analysis. This technique is typically performed by
      using a small RPLC precolumn to capture and concentrate analytes as they elute
      from the immunoextraction column; however, there is little information on the
      conditions required for optimizing this interface. This study examined the
      behavior of this interface by using 2,4-dichlorophenoxyacetic acid (2,4-D) and
      related herbicides as model analytes. It was found that analyte dissociation from
      immunoextraction columns followed first-order decay and that the elution of these
      analytes through the immunoextraction/RPLC interface gave an exponentially
      modified Gaussian profile. Computer simulations were used to see how analyte
      elution through the interface changed with different dissociation and retention
      conditions. Several guidelines were developed from this work that could be used
      for developing and optimizing on-line immunoextraction/RPLC systems for other
      chemicals of environmental or agricultural interest.

PMID- 17455949
TI  - Development of an enzyme-linked immunosorbent assay for the detection of
      pentachloronitrobenzene residues in environmental samples.
AB  - A competitive enzyme-linked immunosorbent assay (ELISA) for
      pentachloronitrobenzene (PCNB), a fungicide and chemical intermediate, was
      developed using a polyclonal antiserum produced against a hapten-protein
      conjugate of pentachlorophenoxypropionic acid-bovine serum albumin (BSA). An
      indirect competitive ELISA of PCNB showed an IC50 of 37 ng/mL and a limit of
      detection (LOD) of 7 ng/mL. The ELISA can tolerate up to 10% (v/v) methanol, 5%
      (v/v) acetonitrile, or 5% (v/v) acetone without significant fluctuation of Amax
      and IC50. The assay sensitivity showed little change in a range of pH from 6 to 8
      and concentrations of 0.05-0.2 M NaCl in the assay buffer. Very low cross
      reactivities were observed for some structurally related compounds except for
      hexachlorobenzene (12%). The average recoveries of PCNB from fortified well
      water, river water, and soil samples were in ranges of 88-94, 80-91, and 70-81%,
      respectively. The correlations between the gas chromatographic and ELISA results
      were excellent (r 2 >or= 0.97, slopes from 0.86 to 1.10) for those fortified
      samples. The ELISA is a good alternative tool for monitoring PCNB residues in
      environmental samples.

PMID- 17455950
TI  - Eastern blotting and immunoaffinity concentration using monoclonal antibody for
      ginseng saponins in the field of traditional chinese medicines.
AB  - Ginsenosides separated by silica gel TLC blotted to a PVDF membrane that was
      treated with a NaIO4 solution followed by bovine serum albumin (BSA) resulted in
      a ginsenoside-BSA conjugate on a PVDF membrane. The blotted spots were stained by
      anti-ginsenoside Rb1 (G-Rb1) and -Rg1 (G-Rg1) monoclonal antibodies (MAbs). The
      newly established immunostaining method, Eastern blotting, was applied for the
      determination of ginsenosides possessing protopanaxadiol and/or protopanaxatriol
      in the traditional Chinese medicine (TCM). This method developed a new way to
      separate the ginsenoside molecule into two functional parts using a simple and
      well-known chemical reaction. The sugar parts were oxidized by NaIO4 to give
      dialdehydes, which reacted with amino groups of the protein and covalently bound
      to the adsorbent PVDF membrane. The MAb bound to the aglycon part of the
      ginsenoside molecule for immunostaining. Double staining of Eastern blotting for
      ginsenosides using anti-G-Rb1 and -Rg1 MAbs promoted complete identification of
      ginsenosides in Panax species. The immunoaffinity concentration of G-Rb1 was
      deteremined by immunoaffinity column conjugated with anti-G-Rb1 MAb leading to
      the knock-out extract, which will be useful for the pharmacological
      investigation. To concentrate and determine G-Rb1 in P. japonicus, the crude
      extract of P. japonicus was fractionated by immunoaffinity column conjugated with
      anti-G-Rb1 MAb. Two ginsenosides, chikusetsusaponins III and IV having
      protopanaxadiol as an aglycon, were identified by Eastern blotting, although it
      was expected that G-Rb1 might be a component of P. japonicus by enzyme-linked
      immunosorbent assay (ELISA) analysis.

PMID- 17455951
TI  - Formation of the thiocyanate conjugate of chlorogenic acid in coffee under acidic
      conditions in the presence of thiocyanate and nitrite: possible occurrence in the
      stomach.
AB  - The objective of the present study was to elucidate how chlorogenic acid in
      coffee was transformed under acidic conditions simulating the mixture of saliva
      and gastric juice. When coffee was incubated in acidified saliva that contained
      nitrite and SCN-, in addition to nitric oxide (NO), four major components were
      detected. Two of the four components (components 3 and 4) were generated when
      chlorogenic acid was incubated in acidified saliva and when incubated in an
      acidic buffer solution in the presence of both nitrite and SCN-. By the
      incubation of chlorogenic acid in acidic nitrite in the absence of SCN-,
      components 3 and 4 were not formed but the quinone of chlorogenic acid and
      nitrated chlorogenic acid were formed. The result indicates that SCN- was
      indispensable for nitrous acid induced formation of components 3 and 4. Component
      4 was isolated and its structure was determined to be (E)-5'-(3-(7-hydroxy-2
      oxobenzo[d] [1,3]oxathiol-4-yl)acryloyloxy)quinic acid. Component 3, which was
      suggested to be 2-thiocyanatochlorogenic acid, seemed to be formed by the
      reaction between SCN- and the quinone of chlorogenic acid. As it has been
      reported that the quinone of chlorogenic acid can react with thiols and can
      decompose producing H2O2, the formation of component 4 can reduce the toxic
      effects of the quinone of chlorogenic acid.

PMID- 17455952
TI  - Effect of processing on the phytochemical profiles and antioxidant activity of
      corn for production of masa, tortillas, and tortilla chips.
AB  - The phytochemical profiles (total phenolics, anthocyanins, ferulic acid,
      carotenoids) and antioxidant activities of five types of corn (white, yellow,
      high carotenoid, blue, and red) processed into masa, tortillas, and tortilla
      chips were studied. The nixtamalization process significantly (p < 0.05) reduced
      total phenolics and antioxidant activities when compared to raw grains.
      Nixtamalized grains exhibited higher concentration of free phenolics and soluble
      conjugated ferulic acid and had lower concentrations of bound phenolics and
      ferulic acid than unprocessed grains. Among processed products, there was little
      difference in the phytochemical contents and antioxidant activities. Among types
      of corn, the highest concentrations of total phenolics, ferulic acid, and
      antioxidant activity were observed in the high-carotenoid genotype followed by
      the regular yellow counterpart. The white corn contained the lowest amount of
      total phenolics and antioxidant activity. The pigmented blue corn had the highest
      anthocyanin concentration followed by the red counterpart. These findings suggest
      that lime-cooking significantly reduced the phytochemical content of nixtamalized
      products but released phenolics and ferulic acid.

PMID- 17455953
TI  - Single-bead immunoassays using magnetic microparticles and spectral-shifting
      quantum dots.
AB  - This paper reports a single-bead immunoassay method based on the combined use of
      magnetic microparticles (MMPs) for target capturing/enrichment and antibody
      conjugated semiconductor quantum dots (QDs) for fluorescence detection. In
      comparison with organic dyes and fluorescent proteins, QDs exhibit unique optical
      properties such as size-tunable fluorescence emission (spectral shifting), large
      absorption coefficients, improved brightness, and superior photostability.
      Magnetic beads, composed of iron oxide nanoparticles embedded in polymeric
      matrices, provide a platform for rapid capturing and enrichment of biomolecules
      and pathogens in dilute biological and environmental samples. However, a major
      problem in using magnetic beads for fluorescence immunoassays is that the bead's
      autofluorescence strongly interferes with the target detection signal. This
      spectral overlapping problem can be overcome by using semiconductor QDs as a new
      class of spectral-shifting labels. By shifting the QD emission signals away from
      the bead autofluorescence, it is possible to detect biomolecular antigens such as
      tumor necrosis factor (TNF-alpha) at femtomolar (10-15 M) concentrations when the
      target molecules are captured and enriched on the magnetic bead surface. This
      sensitivity is almost 1000 times higher that that of traditional immunoabsorbent
      assays and more than 100 times higher than immunofluorescent assays using organic
      dyes.

PMID- 17455954
TI  - Melanoidins from coffee infusions. Fractionation, chemical characterization, and
      effect of the degree of roast.
AB  - A method involving fractionation in ethanol aqueous solutions, anion exchange
      chromatography, and immobilized copper chelating chromatography was developed to
      obtain high molecular weight anionic melanoidin populations from coffee
      infusions. Six anionic fractions with different physicochemical properties
      (ethanol solubility and chelating ability) and chemical composition regarding
      carbohydrate as well as protein nature and content were isolated. Fractions with
      similar chemical composition were obtained for light-, medium-, and dark-roasted
      coffee infusions. These melanoidin fractions accounted for 30-33% of the cold
      water soluble high molecular weight material, independently of the degree of
      roast in coffee. The nature and abundance of the different polysaccharides in
      each fraction were dependent on their ethanol solubility. The 50% ethanol
      insoluble melanoidin populations contained mostly galactomannan-like
      carbohydrates, and the fractions obtained with 75% ethanol contained mostly
      arabinogalactan-like carbohydrates. The melanoidin populations with chelating
      properties presented significantly lower carbohydrate content and, from these,
      the 75% ethanol soluble fractions were almost devoid of carbohydrate material.
      The results obtained suggest that the chelating ability of these coffee
      melanoidins is modulated by their carbohydrates.

PMID- 17455955
TI  - Introduction, recent advances in immunochemistry and their application to
      agrochemicals.

PMID- 17455956
TI  - Influence of sulfur fertilization on the amounts of free amino acids in wheat.
      correlation with baking properties as well as with 3-aminopropionamide and
      acrylamide generation during baking.
AB  - Sulfur (S) fertilization has been long-known to influence the amounts of total
      free amino acids in plants. To determine the impact of S deficiency in wheat on
      the concentration of, in particular, free asparagine, the spring wheat cultivar
      'Star' was grown in a laboratory scale (5 L pot) at five different levels of S
      fertilization. After maturity, the kernels were milled into white flours (1-5)
      and analyzed for their contents of total S and total nitrogen as well as for free
      amino acids and glucose, fructose, maltose, and sucrose. Extremely high
      concentrations of free asparagine (Asn; 3.9-5.7 g/kg) were determined in flours 1
      and 2 (30 and 60 mg of S), whereas much lower amounts (0.03-0.4 g/kg) were
      present in flours grown at higher S levels. The amounts of the reducing
      carbohydrates were, however, scarcely affected by S fertilization. In agreement
      with the high amount of Asn in flours 1 and 2, heating of both flours led to the
      generation of very high amounts of acrylamide (1.7-3.1 mg/kg) as well as of 3
      aminopropionamide (40-76 mg/kg). Similar concentrations were measured in
      crispbread prepared from both flours. Application of rheological measurements on
      doughs prepared from each flour and a determination of the loaf volume of bread
      baked therefrom clearly indicated that flours 1 and 2 would be excluded from
      commercial bread processing due to their poor technological properties. Two
      commercial flours showed relatively low concentrations of acrylamide after a
      thermal treatment.

PMID- 17455957
TI  - Clarification of the C-35 stereochemistries of dinophysistoxin-1 and
      dinophysistoxin-2 and its consequences for binding to protein phosphatase.
AB  - Okadaic acid analogues are well known as protein phosphatase inhibitors and occur
      naturally in marine shellfish feeding on dinoflagellates of the genus Dinophysis,
      leading to diarrhetic shellfish poisoning of shellfish consumers. Knowledge of
      the correct structures for these toxins is important in understanding their
      toxicology, biochemistry, and biosynthesis. We have performed extensive NMR
      analyses on okadaic acid (1), dinophysistoxin-1 (DTX-1), and dinophysistoxin-2
      (DTX-2) obtained from natural sources. Consequently, we were able to
      unambiguously deduce the stereochemistries at C-35 for DTX-1 and DTX-2 based on
      analysis of NMR coupling constants and NOE interactions. Our results revealed
      that DTX-2 (3) has a stereochemistry opposite to that of DTX-1 (2) at C-35.
      Molecular modeling of the docking of 1-3 with protein phosphatase-1 and protein
      phosphatase 2A (PP2A) suggested that the reduced affinity of DTX-2 for PP2A may
      be due to the newly defined stereochemistry at the 35-methyl group. The
      implications of these findings for biosynthesis and toxicology are discussed.

PMID- 17455959
TI  - Preparation of novel fluoroalkyl-end-capped 2-acrylamido-2-methylpropanesulfonic
      acid cooligomeric nanoparticles containing adamantane units possessing a lower
      critical solution temperature characteristic in organic media.
AB  - Fluoroalkyl-end-capped 2-acrylamido-2-methylpropanesulfonic acid cooligomers
      containing adamantyl segments were prepared by reaction of fluoroalkanoyl
      peroxide with 2-acrylamido-2-methylpropanesulfonic acid (AMPS) and 3-hydroxy-1
      adamantyl acrylate (Ad-HAc). These obtained fluorinated AMPS-Ad-HAc cooligomers
      were found to form nanometer-size-controlled fine particles not only in water but
      also in a large variety of traditionally organic solvents. In addition, these
      fluorinated cooligomeric nanoparticles showed a good dispersibility in these
      solvents. Interestingly, the size of these fluorinated nanoparticles is extremely
      sensitive to solvent changes, and an increase of the particle size was observed
      in the solvents, in which the dielectric constant is higher or lower. More
      interestingly, these fluorinated AMPS-Ad-HAc cooligomeric nanoparticles exhibited
      a lower critical solution temperature around 52 degrees C in an organic medium
      (tert-butyl alcohol).

PMID- 17455958
TI  - HPLC-ESI+-MS/MS analysis of N7-guanine-N7-guanine DNA cross-links in tissues of
      mice exposed to 1,3-butadiene.
AB  - 1,3-butadiene (BD) is a major industrial chemical used in rubber and plastics
      production and is recognized as an animal and human carcinogen. Although the
      exact mechanism of BD-induced carcinogenesis is unknown, chemical reactions of
      epoxide metabolites of BD with DNA to form nucleobase adducts are likely to
      contribute to multistage carcinogenesis. Among BD-derived epoxy metabolites,
      1,2:3,4-diepoxybutane (DEB) appears to be the most genotoxic and carcinogenic,
      probably because of its bifunctional nature. Initial DNA alkylation by DEB
      produces N7-(2'-hydroxy-3',4'-epoxybut-1'-yl)guanine monoadducts, which can then
      be hydrolyzed to N7-(2',3',4'-trihydroxy-1'-yl)guanine or can react with another
      site in double-stranded DNA to form 1,4-bis(guan-7-yl)-2,3-butanediol (bis-N7G
      BD) cross-links. While (2',3',4'-trihydroxy-1'-yl)guanine lesions have been
      previously quantified in vivo, they cannot be used as a biomarker of DEB because
      the same lesions are also formed by another, more prevalent BD metabolite, 1,2
      epoxy-3,4-butanediol. In contrast, bis-N7G-BD can only be formed from DEB,
      potentially providing a specific biomarker of DEB formation. We have developed a
      quantitative HPLC-ESI+-MS/MS method for measuring racemic and meso forms of bis
      N7G-BD in DNA extracted from tissues of BD-exposed laboratory animals. In our
      approach, bis-N7G-BD adducts are released from DNA as free bases by neutral
      thermal hydrolysis, purified by solid-phase extraction, and subjected to HPLC
      ESI+-MS/MS analysis. Selected reaction monitoring is performed by following the
      loss of a guanine moiety from protonated molecules of bis-N7G-BD and the
      formation of protonated guanine under collision-induced dissociation.
      Quantitative analysis of racemic and meso forms of bis-N7G-BD is based on isotope
      dilution with the corresponding 15N-labeled internal standards. The lower limit
      of quantification of our current method is 10-20 fmol/0.1 mg of DNA. The accuracy
      and precision of the new method were determined by spiking control mouse liver
      DNA with racemic and meso forms of bis-N7G-BD (10 fmol each), followed by sample
      processing and HPLC-ESI+-MS/MS analysis. Calculated amounts of racemic and meso
      forms of bis-N7G-BD were within 20% of the theoretical value (9.7 +/- 2 and 9.2
      +/- 1.9 fmol, respectively, N = 4). DNA extracted from liver and lung tissues of
      mice exposed to 625 ppm butadiene for 5 days contained 3.2 +/- 0.4 and 1.8 +/-
      0.5 racemic adducts per 10(6) guanines, respectively, while the amounts of meso
      bis-N7G-BD were below the detection limits of our method (1 per 10(7) guanines).
      Control animals did not contain either bis-N7G-BD lesion. Sensitive and specific
      quantitative methods for bis-N7G-BD analysis developed in this work provide a
      unique biomarker of DEB-induced DNA alkylation following exposure to BD.

PMID- 17455960
TI  - Adsorption behavior of DNA-wrapped carbon nanotubes on self-assembled monolayer
      surfaces.
AB  - We have examined the adsorption of DNA-wrapped single-walled carbon nanotubes
      (DNA-SWNTs) on hydrophobic, hydrophilic, and charged surfaces of alkylthiol self
      assembled monolayers (SAMs) on gold. Our goal is to understand how DNA-SWNTs
      interact with surfaces of varying chemical functionality. These samples were
      characterized using reflection absorption FTIR (RAIRS), X-ray photoelectron
      spectroscopy (XPS), and Raman spectroscopy. We have found that DNA-SWNTs
      preferentially adsorb to positively charged amine-terminated SAMs and to bare
      gold surfaces versus hydrophobic methyl-terminated or negatively charged
      carboxylic acid-terminated SAMs. Examination of the adsorption on gold of single
      strand DNA (ssDNA) of the same sequence used to wrap the SWNTs suggests that the
      DNA wrapping plays a role in the adsorption behavior of DNA-SWNTs.

PMID- 17455961
TI  - Transient interfacial patterns and instabilities associated with liquid film
      adhesion and spreading.
AB  - A surface force apparatus was used to study surface shape changes during the
      adhesion and spreading of a polymer melt on a bare mica surface. Transient
      fingers were observed during the initial, rapid spreading process, pointing
      radially out from the initial adhesive contact point. The fingers had microscopic
      widths and lengths but submicroscopic thicknesses. They eventually disappeared,
      leaving a more slowly growing circular neck with a smooth, featureless polymer
      air surface. The mean radius of the spreading meniscus (neck) was found to follow
      a scaling relationship with time of the form (ri + ro)/2 proportional, variant
      tn, with n = 0.128, while the ends of the fingers grew according to ro
      proportional, variant tn, with n = 0.10. These rates agree with the values of n =
      0.100-0.125 predicted by classical wetting theories for circular macroscopic
      droplets (i.e., radially symmetric, without fingers) spreading on a solid
      surface. The lifetime of the transient fingering patterns increases with the
      polymer viscosity as tau proportional, variant etan, with n = 2.1 +/- 0.2. A
      circular trough or depression in the film was observed just beyond where the
      fingers ended, which appears to be a source of the material for the advancing
      fingers. In addition, beyond the trough, circular ripples/waves were observed on
      the polymer melt film surface. Such patterns may arise quite generally whenever a
      perturbation occurs that changes the local forces, thereby inducing a bulge or
      depression in a liquid film or surface. Thus, we observe similar fingers and
      ripples/waves during the spreading of liquid polybutadiene on (the immiscible and
      more viscous) liquid poly(dimethylsiloxane), suggesting that the phenomenon may
      exist in various liquid adhesion and spreading situations. For low viscosity
      liquids such as water and low molecular weight oils, our scaling relations
      suggest that the transient patterns will exist for only a few microseconds; this
      is likely the reason for why they have not yet been observed.

PMID- 17455962
TI  - Synthesis of dendron-protected porphyrin wires and preparation of a one
      dimensional assembly of gold nanoparticles chemically linked to the pi-conjugated
      wires.
AB  - A one-dimensional assembly of gold nanoparticles chemically bonded to pi
      conjugated porphyrin polymers was prepared on a chemically modified glass surface
      and on an undoped naturally oxidized silicon surface by the following methods: pi
      conjugated porphyrin polymers were prepared by oxidative coupling of 5,15
      diethynyl-10,20-bis-((4-dendron)phenyl) porphyrin (6), and its homologues (larger
      than 40-mer) were collected by analytical gel permeation chromatography (GPC).
      The porphyrin polymers (>40-mer) were deposited using the Langmuir-Blodgett (LB)
      method on substrate surfaces, which were then soaked in a solution of gold
      nanoparticles (2.7 +/- 0.8 nm) protected with t-dodecanethiol and 4
      pyridineethanethiol. The topographical images of the surface observed by tapping
      mode atomic force microscopy (AFM) showed that the polymers could be dispersed on
      both substrates, with a height of 2.8 +/- 0.5 nm on the modified glass and 3.1 +/
      0.5 nm on silicon. The height clearly increased after soaking in the gold
      nanoparticle solution, to 5.3 +/- 0.5 nm on glass and 5.4 +/- 0.7 nm on silicon.
      The differences in height (2.5 nm on glass and 2.3 nm on silicon) corresponded to
      the diameter of the gold nanoparticles bonded to the porphyrin polymers. The
      distance between gold nanoparticles observed in scanning electron microscopic
      images was ca. 5 nm, indicating that they were bonded at every four or five
      porphyrin units.

PMID- 17455963
TI  - Nanografting of alkanethiols by tapping mode atomic force microscopy.
AB  - Nanografting, an atomic force microscopy (AFM) based nanolithography technique,
      is becoming a popular method for patterning self-assembled monolayers (SAMs). In
      this technique, a nanoscale patch of a thiol-on-gold SAM is exchanged with a
      different thiol by the action of an AFM tip operated in contact mode at high
      load. The results are then imaged in topographic or lateral force microscopy
      again at low values of the load. One of the problems of contact mode nanografting
      is that monolayers of large molecules such as proteins are likely to be deformed,
      damaged, or even removed from the surface by contact mode imaging even when small
      loads are used. Furthermore, we need to note that the stiffness of the
      cantilevers used in contact mode is different than that of the cantilevers used
      in tapping mode and that tip changing in the course of an experiment can be quite
      inconvenient. Here, we show that a monolayer on a gold substrate can be
      nanografted using tapping mode AFM (also referred to as amplitude modulation AFM)
      rather than the commonly used contact mode. While the grafting parameters are
      somewhat trickier to choose, the results demonstrate that nanografting in tapping
      mode can make patches of the same quality as those made by contact mode,
      therefore allowing for gentle imaging of the grafted molecules and the whole SAM
      without changing the microscope tip.

PMID- 17455964
TI  - Two-dimensional crystal growth from undersaturated solutions.
AB  - The solubility of a substance is commonly understood as the minimum concentration
      necessary for the condensation of a solid phase from solution. Here we report the
      nucleation and growth of ionic compounds from aqueous concentrations on the order
      of 0.1 times the solubility. The condensation is catalyzed by a foreign
      substrate, and the new phase grows as a crystalline monolayer. Undersaturated
      growth is observed only in cases where the dissolved compound is isomorphic with
      the substrate and the interaction strength between a dissolved-ion/substrate-ion
      pair exceeds that between the two dissolved ions. These results are consistent
      with a simple model in which favorable ion-surface interactions lead to ion
      enrichment and supersaturation in the two-dimensional interfacial zone.

PMID- 17455965
TI  - Oil-in-water nanocontainers as low environmental impact cleaning tools for works
      of art: two case studies.
AB  - A novel class of p-xylene-in-water microemulsions mainly based on nonionic
      surfactants and their application as low impact cleaning tool in cultural
      heritage conservation is presented. Alkyl polyglycosides (APG) and Triton X-100
      surfactants allow obtaining very effective low impact oil-in-water (o/w)
      microemulsions as alternatives to pure organic solvents for the removal of
      polymers (particularly Paraloid B72 and Primal AC33) applied during previous
      conservation treatments. The ternary APG/p-xylene/water microemulsions have been
      characterized by quasi elastic light scattering to obtain the hydrodynamic radius
      and the polydispersity of the microemulsion droplets. Laplace inversion of the
      correlation function CONTIN analysis provided evidence of acrylic copolymers
      solubilization into the oil nanodroplets. Contact angle, Fourier transform
      infrared (FTIR), and scanning electron microscopy/energy-dispersive spectroscopy
      (SEM/EDS) data confirmed that microemulsions were effective in removing polymer
      coatings. The phase diagram of APG microemulsions showed that a reduction >90%
      (compared to the conventional cleaning methods) of the organic solvent can be
      achieved by using o/w microemulsions. The microemulsions were successfully tested
      in two real cases: (1) the APG based microemulsion was used in a Renaissance
      painting by Vecchietta in Santa Maria della Scala, Siena, Italy, degraded by the
      presence of a polyacrylate coating applied during a previous restoration and (2)
      a Triton X-100 oil-in-water microemulsion containing (NH4)2CO3 in the water
      continuous phase. The association of ammoniun carbonate to the microemusion led
      to the swelling of an organic deposit (mainly asphaltenes deposited on the fresco
      in the Oratorio di San Nicola al Ceppo in Florence, still contamined by the water
      of the Arno river during the 1966 flood) and a very efficient removal of highly
      insoluble inorganic deposits (mainly gypsum) strongly associated to asphaltenes.
      These innovative systems are very attractive for the low amount of organic
      solvent used to extract the polymers or highly insoluble substances as the
      asphaltene and the very efficient and mild impact of the cleaning procedure on
      the fragile painted surfaces.

PMID- 17455966
TI  - Carbon nanotubes contain residual metal catalyst nanoparticles even after washing
      with nitric acid at elevated temperature because these metal nanoparticles are
      sheathed by several graphene sheets.
AB  - It is demonstrated that multiwalled (MWCNT) and single-walled (SWCNT) carbon
      nanotube materials contain residual metal impurities (Fe, Ni, Co, Mo) even after
      prolonged periods of "washing" with concentrated nitric acid at temperature of 80
      degrees C. Transmission electron microscopy (TEM) and high-resolution TEM (HR
      TEM) reveals that this is because such metal impurities are intercalated in the
      nanotube channel (in the case of MWCNT) or in the "bamboo" segment of the
      nanotube (in the case of "bamboo"-like MWCNT), or they create graphene sheet
      protected metal core/shell nanoparticles (in the case of SWCNT). TEM/energy
      dispersive X-ray spectroscopy (TEM/EDS) elucidate that residual metal impurities
      presented in "washed" carbon nanotube materials are in some cases in the form of
      metal alloys or that there can be several different pure metal nanoparticles
      presented in one CNT material. It is shown by thermogravimetric analysis that
      "washing" with concentrated nitric acid removes up to 88% (w/w) of metal catalyst
      nanoparticles from as-received carbon nanotubes and that such removal has in some
      cases a significant effect on the electrochemical reduction of hydrogen peroxide.

PMID- 17455967
TI  - DHA-induced changes of supported lipid membrane morphology.
AB  - Docosahexaenoic acid (DHA) is a polyunsaturated long fatty acid known to have
      fundamental effects on cell membrane function. Here, the effect of DHA on
      phosphocholine-supported lipid bilayers was measured using the quartz crystal
      microbalance with dissipation monitoring (QCM-D) technique. Above a concentration
      of 60 muM (i.e., near the critical micelle concentration), DHA had drastic
      effects on the viscoelastic properties of the supported membranes, suggesting a
      more complex process and structure than simple insertion of molecules in the
      bilayer. Fluorescence microscopy revealed the spontaneous formation of elongated
      out-growths from the bilayers, which were remarkable for their length (
      approximately 100 mum) and extensive coverage of the surface. These results
      demonstrate the applicability of QCM-D as a method to screen for conditions where
      membrane remodeling occurs but also that complementary techniques are required to
      describe in more detail the changes in viscoelastic properties of the membrane.
      These results are highly relevant for the present rapid development in the field
      of model lipid membranes aiming toward increased knowledge about processes
      occurring at biological surfaces.

PMID- 17455968
TI  - Covalent biofunctionalization of silicon nitride surfaces.
AB  - Covalently attached organic monolayers on etched silicon nitride (SixN4; x >/= 3)
      surfaces were prepared by reaction of SixN4-coated wafers with neat or solutions
      of 1-alkenes and 1-alkynes in refluxing mesitylene. The surface modification was
      monitored by measurement of the static water contact angle, XPS, IRRAS, AFM, and
      ToF-SIMS, and evidence for the formation of Si-C bonds is presented. The etching
      can be achieved by dilute HF solutions and yields both Si-H and N-H moieties. The
      resulting etched SixN4 surfaces are functionalized by terminal carboxylic acid
      groups in either of two ways: (a) via attachment of a 10-undecenoic acid 2,2,2
      trifluoroethyl ester (trifluoro ethanol ester) and subsequent thermal acid
      hydrolysis; (b) through attachment of a photocleavable ester, and subsequent
      photochemical cleavage, as this would allow photopatterned functionalized SixN4.
      The carboxylic acids are successfully used for the attachment of oligopeptides
      (aspartame) and complete proteins using EDC/NHS chemistry. Finally, an amino
      terminated organic monolayer can be formed by reaction of HF-treated SixN4
      surfaces with a N-(omega-undecylenyl)phthalimide, which yields an amino
      terminated surface upon deprotection with hydrazine.

PMID- 17455969
TI  - Mass spectrometric analysis of high-mobility group proteins and their post
      translational modifications in normal and cancerous human breast tissues.
AB  - High-mobility group (HMG) A1 proteins including HMGA1a and HMGA1b are chromosomal
      proteins that function in a variety of cellular processes such as cell growth,
      transcription regulation, neoplastic transformation, and progression.
      Overexpression of HMGA1 proteins has been associated with almost every type of
      cancer cells. Post-translational modifications (PTMs) of HMGA1 proteins in
      different types of human cancer cell lines have been extensively explored over
      the past decade. Here, we extended the identification of PTMs of HMGA1 proteins
      to human breast tumor tissue specimens with different carcinoma progression
      stages (metastatic and primary cancer) as well as the paired adjacent normal
      breast tissues. In this regard, we employed tandem mass spectrometry to examine
      the nature and sites of PTMs of HMGA1 proteins isolated from cancerous/normal
      human breast tissues. Novel PTMs of HMGA1a protein, that is, monomethylation at
      Lys30 and Lys54 as well as monophosphorylation at Ser43 and Ser48, were detected
      in cancer tissues. In these cancer tissues, we also found C-terminal constitutive
      phosphorylation in HMGA1a and HMGA1b as well as mono- and dimethylation of Arg25
      in HMGA1a, which were previously found to be present in these proteins isolated
      from human cancer cell lines. Furthermore, a more complex spectrum of PTMs on
      HMGA1 proteins was correlated with a more aggressive malignancy in human breast
      cancer tissues.

PMID- 17455970
TI  - Tyrosyl rotamer interconversion rates and the fluorescence decays of N
      acetyltyrosinamide and short tyrosyl peptides.
AB  - It has long been recognized that the fluorescence lifetimes of amino acid
      residues such as tyrosine and tryptophan depend on the rotameric configuration of
      the aromatic side chain, but estimates of the rate of interchange of rotameric
      states have varied widely. We report measurements of the rotameric populations
      and interchange rates for tyrosine in N-acetyltyrosinamide (NATyrA), the
      tripeptide Tyr-Gly-Gly (YGG), and the pentapeptide Leu-enkephalin (YGGFL). The
      fluorescence lifetimes were analyzed to determine the rotameric interchange rates
      in the context of a model incorporating exchange among three rotameric states.
      Maximum entropy method analysis verified the presence of three fluorescence decay
      components for YGGFL and two for YGG and NATyrA. Rotameric exchange between the
      gauche(-) and trans states occurred on the nanosecond time scale, whereas
      exchange with the gauche(+) state occurred on a longer time scale. Good agreement
      was obtained with rotameric populations and exchange rates from molecular
      dynamics simulations. Quenching by iodide was used to vary the intrinsic
      fluorescence lifetimes, providing additional constraints on the determined
      interchange rates. The temperature dependence was measured to determine barriers
      to exchange of the two most populated rotamers of 3, 5, and 7 kcal/mol for
      NATyrA, YGG, and YGGFL, respectively.

PMID- 17455971
TI  - On the derivation of Young's equation for sessile drops: nonequilibrium effects
      due to evaporation.
AB  - Sessile liquid drops have a higher vapor pressure than planar liquid surfaces, as
      quantified by Kelvin's equation. In classical derivations of Young's equation,
      this fact is often not taken into account. For an open system, a sessile liquid
      drop is never in thermodynamic equilibrium and will eventually evaporate.
      Practically, for macroscopic drops the time of evaporation is so long that
      nonequilibrium effects are negligible. For microscopic drops evaporation cannot
      be neglected. When a liquid is confined to a closed system, real equilibrium can
      be established. Experiments on the evaporation of water drops confirm the
      calculations.

PMID- 17455972
TI  - Mechanism of nitrite reduction at T2Cu centers: electronic structure calculations
      of catalysis by copper nitrite reductase and by synthetic model compounds.
AB  - The mechanism of nitrite reduction at the Cu(II) center of both copper nitrite
      reductase and a number of corresponding synthetic models has been investigated by
      using both QM/MM and cluster calculations employing density functional theory
      methods. The mechanism in both cases is found to be very similar. Initially
      nitrite is bound in a bidentate fashion to the Cu(II) center via the two oxygen
      atoms. Upon reduction of the copper center, the two possible coordination modes
      of the protonated nitrite, by either nitrogen or a single oxygen atom, are close
      in energy, with nitrogen coordination probably preferred. Further protonation of
      this species leads to N-O bond cleavage, and an electron transfer from the Cu(I)
      center to the N-O+ ligand, resulting in loss of NO and regeneration of the
      resting state of the enzyme having a bound water molecule.

PMID- 17455973
TI  - Pressure-dependent diffusion coefficients and haven ratios in cation-conducting
      glasses.
AB  - The influence of hydrostatic pressure on diffusion and ionic conduction is
      providing deeper insights into the atomistic mechanisms of ionic motion in
      glasses. We have studied the tracer diffusion of 22Na in a sodium borate glass
      and of 86Rb in a rubidium borate glass as functions of hydrostatic pressures. The
      activation volumes of tracer diffusion are DeltaVD(Rb) = 33.5 cm3 mol-1 and
      DeltaVD(Na) = 6.1 cm3 mol-1. In comparison, the activation volumes of charge
      diffusion obtained recently from the pressure dependence of conductivity are
      smaller: DeltaVsigma(Rb) = 7.2 cm3 mol(-1) and DeltaVsigma(Na) = 2.8 cm3 mol(-1).
      These differences, where (DeltaVD - DeltaVsigma) > 0, imply that the Haven ratios
      decrease with pressure. This effect is particularly significant for the rubidium
      borate glass. Starting from basic equations of linear response theory for mass
      and charge transport, we develop a model that accounts for these experimental
      findings. The difference between the activation volumes, DeltaVD and DeltaVsigma,
      and the pressure-dependent Haven ratios are consequences of collective movements
      of ions in glass, implying a concerted motion of ions in a chain- or caterpillar
      like fashion. In our treatment, it is a vacant site (with ions jumping into it
      successively) that moves along an extended pathway. Hence, we regard vacant sites
      as the carriers of charge and ions as the carriers of diffusing matter. The
      decrease of the Haven ratio with pressure is attributed to the influence of
      pressure on the topology of the conduction pathways, which are progressively
      straightened out with increasing pressure.

PMID- 17455974
TI  - Oxygen-release/storage properties of Ce0.5M0.5O2 (M = Zr, Hf) oxides: interplay
      of crystal chemistry and electronic structure.
AB  - Fluorite-type Ce0.5Zr0.5O2 and Ce0.5Hf0.5O2 have been synthesized by a solution
      combustion route, and their oxygen release and reduction have been investigated
      up to 850 degrees C. On reduction, the zirconium system forms two pyrochlore
      phases, Ce2Zr2O7 (pyrochlore-I) and Ce2Zr2O6.2 (pyrochlore-II), while the hafnium
      system forms only a disordered fluorite phase with the composition
      Ce0.5Hf0.5O1.77, under the same experimental conditions. The crystal structures
      of the reduction products have been characterized by powder X-ray diffraction and
      Rietveld refinement, and their electronic structures have been investigated by
      photoelectron spectroscopy and electrical conductivity measurements. Pyrochlore-I
      (a = 10.6727(4) A) is a semiconductor, while pyrochlore-II (a = 10.6463(8) A) is
      a good conductor (with a nearly temperature independent resistivity of
      approximately 2.5 ohm.cm in the 400-1000 K range). X-ray photoelectron
      spectroscopy (XPS) shows an admixture of Ce(5d,6s) with Zr(4d) and O(2p) and a
      significant density of states near EF in the highly reduced pyrochlore-II phase.
      The changes have been rationalized in terms of a qualitative energy band scheme
      that brings out the special role of zirconium vis-a-vis hafnium in the
      reduction/oxygen release properties of Ce0.5Zr0.5O2 and Ce0.5Hf0.5O2.

PMID- 17455975
TI  - An experimental and theoretical study of the formation of nanostructures of self
      assembled cyanuric acid through hydrogen bond networks on graphite.
AB  - The self-assembly of cyanuric acid into ordered nanostructures on a crystalline
      substrate, highly ordered pyrolytic graphite (HOPG), has been investigated at low
      temperature under ultrahigh vacuum (UHV) conditions by means of scanning
      tunneling microscopy in conjunction with theoretical simulations. Many domains
      with different self-assembly patterns were observed. One such domain represents
      the formation of an open 2D rosette (cyclic) structure from the self-assembly
      process, the first observation of this type of structure for pure cyanuric acid
      on a graphite substrate. Each self-assembled domain exhibits characteristic
      superstructures formed through different hydrogen bond networks at low coverage
      and low deposition rate. Experimental observation of coexistent, two-dimensional
      crystalline structures with distinct hydrogen bond patterns is supported by
      energy minimizations and molecular dynamics calculations, which show multiple
      stable structures for this molecule when self-assembled on graphite.

PMID- 17455976
TI  - Probing the effect of local structure on the thermodynamic redox properties of
      V(+5): a comparison of V2O5 and Mg3(VO4)2.
AB  - Coulometric titration, an electrochemical method for measuring oxidation
      isotherms, has been used to characterize the redox properties of V2O5 and
      Mg3(VO4)2 between 823 and 973 K. V2O5 shows distinct regions in the isotherms
      corresponding to equilibrium with mixtures of V2O3 and V2O4 and of V2O4 and V2O5.
      From this data, the enthalpies for oxidation of V2O3 to V2O4 and for V2O4 to V2O5
      are shown to be -380 +/- 10 and -285 +/- 20 kJ mol-1 O2, respectively. Oxidation
      isotherms for Mg3(VO4)2 exhibit a single step between the oxidized sample (all
      V+5) and a completely reduced sample (all V+3). The enthalpy of oxidation is
      found to increase with the oxidation state of the sample, from -370 +/- 30 kJ mol
      1 O2 at an O:V ratio of 1.5 to -460 +/- 10 kJ mol-1 O2 at an O:V ratio of 2.5.

PMID- 17455977
TI  - Simultaneous binding of minor groove binder and intercalator to dodecamer DNA:
      importance of relative orientation of donor and acceptor in FRET.
AB  - In the present study, steady-state, picosecond time-resolved fluorescence and
      polarization gated anisotropy have been used to establish simultaneous binding of
      an intercalator (ethidium bromide, EtBr) and a minor groove binder (Hoeschst
      33258, H258) to a dodecamer DNA of specific sequence. The Forster resonance
      energy transfer (FRET) studies between the dyes H258 (donor) and EtBr (acceptor)
      in the dodecamer, where the ligands have a particular relative orientation of the
      transition dipoles, in contrast to the cases in sodium dodecyl sulfate (SDS)
      micelles and larger genomic DNA, where the orientations are random, reveal the
      effect of the binding geometry of the ligands in the constrained environment. Our
      study establishes that reconsideration of the value of the orientation factor
      (kappa2) is crucial for correct estimation of the donor-acceptor distance when
      the ligands are simultaneously bound to a specific region of biological
      macromolecules.

PMID- 17455978
TI  - Aurantiomides A-C, quinazoline alkaloids from the sponge-derived fungus
      Penicillium aurantiogriseum SP0-19.
AB  - Three new quinazoline alkaloids, aurantiomides A (1), B (2), and C (3), along
      with the known metabolite anacine (4) were isolated from the sponge-derived
      fungus strain Penicillium aurantiogriseum SP0-19 by bioassay-guided
      fractionation. Their structures were elucidated by spectroscopic and chemical
      methods. Their absolute configurations were deduced by comparison of their Cotton
      effects with anacine (4) and by chemical transformations. Compounds 2 and 3
      showed moderate cytotoxicities against HL-60, P388 and BEL-7402, P388 cell lines,
      respectively.

PMID- 17455979
TI  - Additional scalarane sesterterpenes from the sponge Phyllospongia papyracea.
AB  - A chemical investigation of the marine sponge Phyllospongia papyracea, collected
      in Papua New Guinea, initiated by the screening result of a beta-catenin/Tcf4
      disruption assay afforded six new bishomoscalarane sesterterpenes containing two
      rare scalaranes with a cyclobutane ring in the molecule, together with one known
      scalarane sesterterpene. The structures of the new compounds were elucidated by
      1D and 2D spectroscopic techniques. The compounds isolated in this study did not
      show activity against the beta-catenin and Tcf4 complex.

PMID- 17455980
TI  - Smiles rearrangements in Ugi- and Passerini-type couplings: new multicomponent
      access to O- and N-arylamides.
AB  - The use of Smiles rearrangement in Ugi- and Passerini-type couplings with
      electron-deficient phenols allows very straightforward multicomponent formation
      of O-aryl- and N-arylamides. Best yields were observed with the highly activated
      o- and p-nitrophenols, salicylic derivatives giving adducts in lower yields. The
      scope of these new reactions is further increased by the successful couplings of
      heterocyclic phenols such as hydroxypyridines and hydroxypyrimidines.

PMID- 17455981
TI  - SmI(2)-promoted radical addition reactions with N-(2-Indolylacyl)oxazolidinones:
      synthesis of bisindole compounds.
AB  - The treatment of N-acyl oxazolidinones of N-benzyl 2-indolecarboxylic acids
      varying in the substitution pattern of the indole ring with samarium diiodide at 
      78 degrees C led to the formation of two indole dimer products. The major product
      isolated in yields from 55 to 59% represents an unsymmetrical dimer arising from
      1,4-addition to the 2-indolecarboxylic acid derivative of a possible ketyl-type
      radical anion intermediate originating from the reduction of the exocyclic
      carbonyl group of the N-acyl oxazolidinone. The minor dimer, represented by a
      symmetrical diketone, was produced in yields ranging from 11 to 23%. Even in the
      presence of an alpha,beta-unsaturated amide, dimerization was the preferred
      pathway rather than the formation of a gamma-keto amide. Upon treatment with
      acid, the unsymmetrical indole dimer cyclized to form a diindolequinone. Finally,
      the N-acyl oxazolidinones of pyrrole-2-carboxylic acid and 3-indolecarboxylic
      acid preferred in both cases to undergo C-C bond formation with an acrylamide in
      the presence of SmI2 rather than dimerization.

PMID- 17455982
TI  - Counterintuitive effect of molecular strength and role of molecular rigidity on
      mechanical properties of layer-by-layer assembled nanocomposites.
AB  - Molecular engineering of multilayered composites by layer-by-layer assembly (LBL)
      made possible easy replication of mechanical properties of nacre. Taking
      advantage of the ability of LBL to finely control the structure of the composite,
      one can further improve the mechanical properties of the multilayers, e.g.,
      increase the strength and stiffness, and gain better understanding of the
      nanoscale and molecular scale mechanics of the materials critical for a variety
      of advanced technologies. In this study, we have replaced
      poly(diallyldimethylammonium chloride) (PDDA) (sigmaUTS approximately 12 MPa, E
      approximately 0.2 GPa) with a much stronger polysaccharide polycation, chitosan
      (CH, sigmaUTS approximately 108 MPa, E approximately 2 GPa), considering that its
      superior molecular strength will improve the macroscale mechanical properties of
      the nanocomposite: strength and stiffness. Free-standing films of the CH and
      montmorillonite (MTM) have been successfully made, and the resulting films
      revealed high uniformity with very high loading of MTM closely comparable to that
      in the natural nacre, approximately 80 wt %. Contrary to our expectations and
      theoretical predictions, the CH-MTM composite revealed lower strength and
      stiffness than those of PDDA-MTM and lower strength than CH polymer itself:
      sigmaUTS approximately 80 MPa and E approximately 6 GPa. Analysis of the
      morphology of adsorbing CH chains with atomic force microscopy revealed highly
      elongated molecules, which is opposite to the observations made for PDDA. Plane
      to-plane adhesion showed a factor of approximately 4 lower strength when compared
      to PDDA-MTM nanocomposite. Altogether these facts support the conclusion that CH
      lacks flexibility necessary for strong adhesion and efficient load transfer
      between the organic matrix and MTM platelets. High rigidity of the CH chains does
      not allow them to acquire a conformation necessary for maximizing the interfacial
      attraction with nanoscale component of the composite. These observations create
      an important foundation in the experimental design of the high-performance
      nanocomposite materials.

PMID- 17455983
TI  - Self-organized, free-standing TiO2 nanotube membrane for flow-through
      photocatalytic applications.
AB  - In the present work we show a simple and robust fabrication process of a dense
      and free-standing membrane consisting of vertically oriented, both-side-open TiO2
      nanotubes. This membrane structure allows direct, size-selective, flow-through
      photocatalytic reactions with a very high efficiency.

PMID- 17455984
TI  - Molecular plasmonics with tunable exciton-plasmon coupling strength in J
      aggregate hybridized Au nanorod assemblies.
AB  - Controlling coherent electromagnetic interactions in molecular systems is a
      problem of both fundamental interest and important applicative potential in the
      development of photonic and opto-electronic devices. The strength of these
      interactions determines both the absorption and emission properties of molecules
      coupled to nanostructures, effectively governing the optical properties of such a
      composite metamaterial. Here we report on the observation of strong coupling
      between a plasmon supported by an assembly of oriented gold nanorods (ANR) and a
      molecular exciton. We show that the coupling is easily engineered and is
      deterministic as both spatial and spectral overlap between the plasmonic
      structure and molecular aggregates are controlled. We think that these results in
      conjunction with the flexible geometry of the ANR are of potential significance
      to the development of plasmonic molecular devices.

PMID- 17455985
TI  - Valid consent for genomic epidemiology in developing countries.

PMID- 17455986
TI  - A man with labile blood pressure.

PMID- 17455987
TI  - Polymorphisms, mutations, and amplification of the EGFR gene in non-small cell
      lung cancers.
AB  - BACKGROUND: The epidermal growth factor receptor (EGFR) gene is the prototype
      member of the type I receptor tyrosine kinase (TK) family and plays a pivotal
      role in cell proliferation and differentiation. There are three well described
      polymorphisms that are associated with increased protein production in
      experimental systems: a polymorphic dinucleotide repeat (CA simple sequence
      repeat 1 [CA-SSR1]) in intron one (lower number of repeats) and two single
      nucleotide polymorphisms (SNPs) in the promoter region, -216 (G/T or T/T) and 
      191 (C/A or A/A). The objective of this study was to examine distributions of
      these three polymorphisms and their relationships to each other and to EGFR gene
      mutations and allelic imbalance (AI) in non-small cell lung cancers. METHODS AND
      FINDINGS: We examined the frequencies of the three polymorphisms of EGFR in 556
      resected lung cancers and corresponding non-malignant lung tissues from 336 East
      Asians, 213 individuals of Northern European descent, and seven of other
      ethnicities. We also studied the EGFR gene in 93 corresponding non-malignant lung
      tissue samples from European-descent patients from Italy and in peripheral blood
      mononuclear cells from 250 normal healthy US individuals enrolled in
      epidemiological studies including individuals of European descent, African
      Americans, and Mexican-Americans. We sequenced the four exons (18-21) of the TK
      domain known to harbor activating mutations in tumors and examined the status of
      the CA-SSR1 alleles (presence of heterozygosity, repeat number of the alleles,
      and relative amplification of one allele) and allele-specific amplification of
      mutant tumors as determined by a standardized semiautomated method of
      microsatellite analysis. Variant forms of SNP -216 (G/T or T/T) and SNP -191 (C/A
      or A/A) (associated with higher protein production in experimental systems) were
      less frequent in East Asians than in individuals of other ethnicities (p <
      0.001). Both alleles of CA-SSR1 were significantly longer in East Asians than in
      individuals of other ethnicities (p < 0.001). Expression studies using bronchial
      epithelial cultures demonstrated a trend towards increased mRNA expression in
      cultures having the variant SNP -216 G/T or T/T genotypes. Monoallelic
      amplification of the CA-SSR1 locus was present in 30.6% of the informative cases
      and occurred more often in individuals of East Asian ethnicity. AI was present in
      44.4% (95% confidence interval: 34.1%-54.7%) of mutant tumors compared with 25.9%
      (20.6%-31.2%) of wild-type tumors (p = 0.002). The shorter allele in tumors with
      AI in East Asian individuals was selectively amplified (shorter allele dominant)
      more often in mutant tumors (75.0%, 61.6%-88.4%) than in wild-type tumors (43.5%,
      31.8%-55.2%, p = 0.003). In addition, there was a strong positive association
      between AI ratios of CA-SSR1 alleles and AI of mutant alleles. CONCLUSIONS: The
      three polymorphisms associated with increased EGFR protein production (shorter CA
      SSR1 length and variant forms of SNPs -216 and -191) were found to be rare in
      East Asians as compared to other ethnicities, suggesting that the cells of East
      Asians may make relatively less intrinsic EGFR protein. Interestingly, especially
      in tumors from patients of East Asian ethnicity, EGFR mutations were found to
      favor the shorter allele of CA-SSR1, and selective amplification of the shorter
      allele of CA-SSR1 occurred frequently in tumors harboring a mutation. These
      distinct molecular events targeting the same allele would both be predicted to
      result in greater EGFR protein production and/or activity. Our findings may help
      explain to some of the ethnic differences observed in mutational frequencies and
      responses to TK inhibitors.

PMID- 17455988
TI  - Genetics of ischaemic stroke among persons of non-European descent: a meta
      analysis of eight genes involving approximately 32,500 individuals.
AB  - BACKGROUND: Ischaemic stroke in persons of European descent has a genetic basis,
      but whether the stroke-susceptibility alleles, the strength of any association,
      and the extent of their attributable risks are the same in persons of non
      European descent remains unanswered. Whether ethnicity itself has a relevant or
      substantial contribution on those effect estimates is controversial. Comparative
      analyses between the ethnic groups may allow general conclusions to be drawn
      about polygenic disorders. METHODS AND FINDINGS: We performed a literature-based
      systematic review of genetic association studies in stroke in persons of non
      European descent. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      determined for each gene-disease association using fixed and random effect
      models. We further performed a comparative genetic analysis across the different
      ethnic groups (including persons of European descent derived from our previous
      meta-analysis) to determine if genetic risks varied by ethnicity. Following a
      review of 500 manuscripts, eight candidate gene variants were analysed among
      32,431 individuals (12,883 cases and 19,548 controls), comprising mainly Chinese,
      Japanese, and Korean individuals. Of the eight candidate genes studied, three
      were associated with ischaemic stroke: the angiotensin I converting enzyme (ACE)
      insertion/deletion (I/D) polymorphism with a mean OR of 1.90 (95% CI 1.23-2.93)
      in the Chinese and 1.74 (95% CI 0.88-3.42) in the Japanese; the summary OR for
      the C677T variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) was 1.18
      (95% CI 0.90-1.56) in Chinese and 1.34 (95% CI 0.87-2.06) in Koreans; and the
      pooled OR for the apolipoprotein E (APOE) gene was 2.18 (95% CI 1.52-3.13) in
      Chinese and 1.51 (95% CI 0.93-2.45) in Japanese. Comparing the commonly
      investigated stroke genes among the Asian groups against studies in persons of
      European descent, we found an absence of any substantial qualitative or
      quantitative interaction for ORs by ethnicity. However, the number of individuals
      recruited per study in the studies of persons of non-European descent was
      significantly smaller compared to studies of persons of European descent, despite
      a similar number of studies conducted per gene. CONCLUSIONS: These data suggest
      that genetic associations studied to date for ischaemic stroke among persons of
      non-European descent are similar to those for persons of European descent. Claims
      of differences in genetic effects among different ethnic populations for complex
      disorders such as stroke may be overstated. However, due to the limited number of
      gene variants evaluated, the relatively smaller number of individuals included in
      the meta-analyses of persons of non-European descent in stroke, and the
      possibility of publication bias, the existence of allele variants with
      differential effects by ethnicity cannot be excluded.

PMID- 17455989
TI  - Earlier mother's age at menarche predicts rapid infancy growth and childhood
      obesity.
AB  - BACKGROUND: Early menarche tends to be preceded by rapid infancy weight gain and
      is associated with increased childhood and adult obesity risk. As age at menarche
      is a heritable trait, we hypothesised that age at menarche in the mother may in
      turn predict her children's early growth and obesity risk. METHODS AND FINDINGS:
      We tested associations between mother's age at menarche, mother's adult body size
      and obesity risk, and her children's growth and obesity risk in 6,009 children
      from the UK population-based Avon Longitudinal Study of Parents and Children
      (ALSPAC) birth cohort who had growth and fat mass at age 9 y measured by dual
      energy X-ray absorptiometry. A subgroup of 914 children also had detailed infancy
      and childhood growth data. In the mothers, earlier menarche was associated with
      shorter adult height (by 0.64 cm/y), increased weight (0.92 kg/y), and body mass
      index (BMI, 0.51 kg/m2/y; all p < 0.001). In contrast, in her children, earlier
      mother's menarche predicted taller height at 9 y (by 0.41 cm/y) and greater
      weight (0.80 kg/y), BMI (0.29 kg/m2/y), and fat mass index (0.22 kg/m2/year; all
      p < 0.001). Children in the earliest mother's menarche quintile (< or =11 y) were
      more obese than the oldest quintile (> or =15 y) (OR, 2.15, 95% CI 1.46 to 3.17;
      p < 0.001, adjusted for mother's education and BMI). In the subgroup, children in
      the earliest quintile showed faster gains in weight (p < 0.001) and height (p <
      0.001) only from birth to 2 y, but not from 2 to 9 y (p = 0.3-0.8). CONCLUSIONS:
      Earlier age at menarche may be a transgenerational marker of a faster growth
      tempo, characterised by rapid weight gain and growth, particularly during
      infancy, and leading to taller childhood stature, but likely earlier maturation
      and therefore shorter adult stature. This growth pattern confers increased
      childhood and adult obesity risks.

PMID- 17455990
TI  - Characteristics and impact of drug detailing for gabapentin.
AB  - BACKGROUND: Sales visits by pharmaceutical representatives ("drug detailing") are
      common, but little is known about the content of these visits or about the impact
      of visit characteristics on prescribing behavior. In this study, we evaluated the
      content and impact of detail visits for gabapentin by analyzing market research
      forms completed by physicians after receiving a detail visit for this drug.
      METHODS AND FINDINGS: Market research forms that describe detail visits for
      gabapentin became available through litigation that alleged that gabapentin was
      promoted for "off-label" uses. Forms were available for 97 physicians reporting
      on 116 detail visits between 1995 and 1999. Three-quarters of recorded visits
      (91/116) occurred in 1996. Two-thirds of visits (72/107) were 5 minutes or less
      in duration, 65% (73/113) were rated of high informational value, and 39%
      (42/107) were accompanied by the delivery or promise of samples. During the
      period of this study, gabapentin was approved by the US Food and Drug
      Administration only for the adjunctive treatment of partial seizures, but in 38%
      of visits (44/115) the "main message" of the visit involved at least one off
      label use. After receiving the detail visit, 46% (50/108) of physicians reported
      the intention to increase their prescribing or recommending of gabapentin in the
      future. In multivariable analysis, intent to increase future use or
      recommendation of gabapentin was associated with receiving the detail in a small
      group (versus one-on-one) setting and with low or absent baseline use of the
      drug, but not with other factors such as visit duration, discussion of "on-label"
      versus "off-label" content, and the perceived informational value of the
      presentation. CONCLUSIONS: Detail visits for gabapentin were of high perceived
      informational value and often involved messages about unapproved uses. Despite
      their short duration, detail visits were frequently followed by physician
      intentions to increase their future recommending or prescribing of the drug.

PMID- 17455991
TI  - Following the script: how drug reps make friends and influence doctors.

PMID- 17455992
TI  - Comparative analysis of alcohol control policies in 30 countries.
AB  - BACKGROUND: Alcohol consumption causes an estimated 4% of the global disease
      burden, prompting governments to impose regulations to mitigate the adverse
      effects of alcohol. To assist public health leaders and policymakers, the authors
      developed a composite indicator-the Alcohol Policy Index-to gauge the strength of
      a country's alcohol control policies. METHODS AND FINDINGS: The Index generates a
      score based on policies from five regulatory domains-physical availability of
      alcohol, drinking context, alcohol prices, alcohol advertising, and operation of
      motor vehicles. The Index was applied to the 30 countries that compose the
      Organization for Economic Cooperation and Development and regression analysis was
      used to examine the relationship between policy score and per capita alcohol
      consumption. Countries attained a median score of 42.4 of a possible 100 points,
      ranging from 14.5 (Luxembourg) to 67.3 (Norway). The analysis revealed a strong
      negative correlation between score and consumption (r = -0.57; p = 0.001): a 10
      point increase in the score was associated with a one-liter decrease in absolute
      alcohol consumption per person per year (95% confidence interval, 0.4-1.5 l). A
      sensitivity analysis demonstrated the robustness of the Index by showing that
      countries' scores and ranks remained relatively stable in response to variations
      in methodological assumptions. CONCLUSIONS: The strength of alcohol control
      policies, as estimated by the Alcohol Policy Index, varied widely among 30
      countries located in Europe, Asia, North America, and Australia. The study
      revealed a clear inverse relationship between policy strength and alcohol
      consumption. The Index provides a straightforward tool for facilitating
      international comparisons. In addition, it can help policymakers review and
      strengthen existing regulations aimed at minimizing alcohol-related harm and
      estimate the likely impact of policy changes.

PMID- 17455993
TI  - Comparing alcohol policies between countries: science or silliness?

PMID- 17455994
TI  - Lethal injection for execution: chemical asphyxiation?
AB  - BACKGROUND: Lethal injection for execution was conceived as a comparatively
      humane alternative to electrocution or cyanide gas. The current protocols are
      based on one improvised by a medical examiner and an anesthesiologist in Oklahoma
      and are practiced on an ad hoc basis at the discretion of prison personnel. Each
      drug used, the ultrashort-acting barbiturate thiopental, the neuromuscular
      blocker pancuronium bromide, and the electrolyte potassium chloride, was expected
      to be lethal alone, while the combination was intended to produce anesthesia then
      death due to respiratory and cardiac arrest. We sought to determine whether the
      current drug regimen results in death in the manner intended. METHODS AND
      FINDINGS: We analyzed data from two US states that release information on
      executions, North Carolina and California, as well as the published clinical,
      laboratory, and veterinary animal experience. Execution outcomes from North
      Carolina and California together with interspecies dosage scaling of thiopental
      effects suggest that in the current practice of lethal injection, thiopental
      might not be fatal and might be insufficient to induce surgical anesthesia for
      the duration of the execution. Furthermore, evidence from North Carolina,
      California, and Virginia indicates that potassium chloride in lethal injection
      does not reliably induce cardiac arrest. CONCLUSIONS: We were able to analyze
      only a limited number of executions. However, our findings suggest that current
      lethal injection protocols may not reliably effect death through the mechanisms
      intended, indicating a failure of design and implementation. If thiopental and
      potassium chloride fail to cause anesthesia and cardiac arrest, potentially aware
      inmates could die through pancuronium-induced asphyxiation. Thus the conventional
      view of lethal injection leading to an invariably peaceful and painless death is
      questionable.

PMID- 17455995
TI  - XDR-TB in South Africa: back to TB sanatoria perhaps?

PMID- 17455996
TI  - XDR-TB in South Africa: revised definition.

PMID- 17455997
TI  - XDR-TB in South Africa: detention is not the priority.

PMID- 17455998
TI  - XDR-TB in South Africa: theory and practice.

PMID- 17455999
TI  - Palladin mutation causes familial pancreatic cancer: absence in European
      families.

PMID- 17456000
TI  - Adherence to TB treatment in Ethiopia: why do patients default?

PMID- 17456001
TI  - Training of peer reviewers: validation of a 5-point rating scale.

PMID- 17456002
TI  - Why most published research findings are false: problems in the analysis.

PMID- 17456003
TI  - PLoS Medicine and publication ethics: when is it research?

PMID- 17456004
TI  - Selective translational repression of truncated proteins from frameshift mutation
      derived mRNAs in tumors.
AB  - Frameshift and nonsense mutations are common in tumors with microsatellite
      instability, and mRNAs from these mutated genes have premature termination codons
      (PTCs). Abnormal mRNAs containing PTCs are normally degraded by the nonsense
      mediated mRNA decay (NMD) system. However, PTCs located within 50-55 nucleotides
      of the last exon-exon junction are not recognized by NMD (NMD-irrelevant), and
      some PTC-containing mRNAs can escape from the NMD system (NMD-escape). We
      investigated protein expression from NMD-irrelevant and NMD-escape PTC-containing
      mRNAs by Western blotting and transfection assays. We demonstrated that
      transfection of NMD-irrelevant PTC-containing genomic DNA of MARCKS generates
      truncated protein. In contrast, NMD-escape PTC-containing versions of hMSH3 and
      TGFBR2 generate normal levels of mRNA, but do not generate detectable levels of
      protein. Transfection of NMD-escape mutant TGFBR2 genomic DNA failed to generate
      expression of truncated proteins, whereas transfection of wild-type TGFBR2
      genomic DNA or mutant PTC-containing TGFBR2 cDNA generated expression of wild
      type protein and truncated protein, respectively. Our findings suggest a novel
      mechanism of gene expression regulation for PTC-containing mRNAs in which the
      deleterious transcripts are regulated either by NMD or translational repression.

PMID- 17456005
TI  - Unmasking activation of the zygotic genome using chromosomal deletions in the
      Drosophila embryo.
AB  - During the maternal-to-zygotic transition, a developing embryo integrates post
      transcriptional regulation of maternal mRNAs with transcriptional activation of
      its own genome. By combining chromosomal ablation in Drosophila with microarray
      analysis, we characterized the basis of this integration. We show that the
      expression profile for at least one third of zygotically active genes is coupled
      to the concomitant degradation of the corresponding maternal mRNAs. The embryo
      uses transcription and degradation to generate localized patterns of expression,
      and zygotic transcription to degrade distinct classes of maternal transcripts.
      Although degradation does not appear to involve a simple regulatory code, the
      activation of the zygotic genome starts from intronless genes sharing a common
      cis-element. This cis-element interacts with a single protein, the Bicoid
      stability factor, and acts as a potent enhancer capable of timing the activity of
      an exogenous transactivator. We propose that this regulatory mode links morphogen
      gradients with temporal regulation during the maternal-to-zygotic transition.

PMID- 17456006
TI  - Odorant-binding proteins OBP57d and OBP57e affect taste perception and host-plant
      preference in Drosophila sechellia.
AB  - Despite its morphological similarity to the other species in the Drosophila
      melanogaster species complex, D. sechellia has evolved distinct physiological and
      behavioral adaptations to its host plant Morinda citrifolia, commonly known as
      Tahitian Noni. The odor of the ripe fruit of M. citrifolia originates from
      hexanoic and octanoic acid. D. sechellia is attracted to these two fatty acids,
      whereas the other species in the complex are repelled. Here, using interspecies
      hybrids between D. melanogaster deficiency mutants and D. sechellia, we showed
      that the Odorant-binding protein 57e (Obp57e) gene is involved in the behavioral
      difference between the species. D. melanogaster knock-out flies for Obp57e and
      Obp57d showed altered behavioral responses to hexanoic acid and octanoic acid.
      Furthermore, the introduction of Obp57d and Obp57e from D. simulans and D.
      sechellia shifted the oviposition site preference of D. melanogaster Obp57d/e(KO)
      flies to that of the original species, confirming the contribution of these genes
      to D. sechellia's specialization to M. citrifolia. Our finding of the genes
      involved in host-plant determination may lead to further understanding of
      mechanisms underlying taste perception, evolution of plant-herbivore
      interactions, and speciation.

PMID- 17456007
TI  - Imaging the impact of cortical microcirculation on synaptic structure and sensory
      evoked hemodynamic responses in vivo.
AB  - In vivo two-photon microscopy was used to image in real time dendrites and their
      spines in a mouse photothrombotic stroke model that reduced somatosensory cortex
      blood flow in discrete regions of cortical functional maps. This approach allowed
      us to define relationships between blood flow, cortical structure, and function
      on scales not previously achieved with macroscopic imaging techniques. Acute
      ischemic damage to dendrites was triggered within 30 min when blood flow over
      >0.2 mm(2) of cortical surface was blocked. Rapid damage was not attributed to a
      subset of clotted or even leaking vessels (extravasation) alone. Assessment of
      stroke borders revealed a remarkably sharp transition between intact and damaged
      synaptic circuitry that occurred over tens of mum and was defined by a transition
      between flowing and blocked vessels. Although dendritic spines were normally ~13
      microm from small flowing vessels, we show that intact dendritic structure can be
      maintained (in areas without flowing vessels) by blood flow from vessels that are
      on average 80 microm away. Functional imaging of intrinsic optical signals
      associated with activity-evoked hemodynamic responses in somatosensory cortex
      indicated that sensory-induced changes in signal were blocked in areas with
      damaged dendrites, but were present ~400 microm away from the border of dendritic
      damage. These results define the range of influence that blood flow can have on
      local cortical fine structure and function, as well as to demonstrate that peri
      infarct tissues can be functional within the first few hours after stroke and
      well positioned to aid in poststroke recovery.

PMID- 17456008
TI  - Gamma oscillations in human primary somatosensory cortex reflect pain perception.
AB  - Successful behavior requires selection and preferred processing of relevant
      sensory information. The cortical representation of relevant sensory information
      has been related to neuronal oscillations in the gamma frequency band. Pain is of
      invariably high behavioral relevance and, thus, nociceptive stimuli receive
      preferred processing. Here, by using magnetoencephalography, we show that
      selective nociceptive stimuli induce gamma oscillations between 60 and 95 Hz in
      primary somatosensory cortex. Amplitudes of pain-induced gamma oscillations vary
      with objective stimulus intensity and subjective pain intensity. However, around
      pain threshold, perceived stimuli yielded stronger gamma oscillations than
      unperceived stimuli of equal stimulus intensity. These results show that pain
      induces gamma oscillations in primary somatosensory cortex that are particularly
      related to the subjective perception of pain. Our findings support the hypothesis
      that gamma oscillations are related to the internal representation of
      behaviorally relevant stimuli that should receive preferred processing.

PMID- 17456009
TI  - Inactivation of Pten in osteo-chondroprogenitor cells leads to epiphyseal growth
      plate abnormalities and skeletal overgrowth.
AB  - To study the role of the Pten tumor suppressor in skeletogenesis, we generated
      mice lacking this key phosphatidylinositol 3'-kinase pathway regulator in their
      osteo-chondroprogenitors. A phenotype of growth plate dysfunction and skeletal
      overgrowth was observed. INTRODUCTION: Skeletogenesis is a complex process
      relying on a variety of ligands that activate a range of intracellular signal
      transduction pathways. Although many of these stimuli are known to activate
      phosphatidylinositol 3'-kinase (PI3K), the function of this pathway during
      cartilage development remains nebulous. To study the role of PI3K during
      skeletogenesis, we used mice deficient in a negative regulator of PI3K signaling,
      the tumor suppressor, Pten. MATERIALS AND METHODS: Pten gene deletion in osteo
      chondrodroprogenitors was obtained by interbreeding mice with loxP-flanked Pten
      exons with mice expressing the Cre recombinase under the control of the type II
      collagen gene promoter (Pten(flox/flox):Col2a1Cre mice). Phenotypic analyses
      included microcomputed tomography and immunohistochemistry techniques. RESULTS:
      MicroCT revealed that Pten(flox/flox):Col2a1Cre mice exhibited both increased
      skeletal size, particularly of vertebrae, and massive trabeculation accompanied
      by increased cortical thickness. Primary spongiosa development and perichondrial
      bone collar formation were prominent in Pten(flox/flox):Col2a1Cre mice, and long
      bone growth plates were disorganized and showed both matrix overproduction and
      evidence of accelerated hypertrophic differentiation (indicated by an altered
      pattern of type X collagen and alkaline phosphatase expression). Consistent with
      increased PI3K signaling, Pten-deficient chondrocytes showed increased phospho
      PKB/Akt and phospho-S6 immunostaining, reflective of increased mTOR and PDK1
      activity. Interestingly, no significant change in growth plate proliferation was
      seen in Pten-deficient mice, and growth plate fusion was found at 6 months.
      CONCLUSIONS: By virtue of its ability to modulate a key signal transduction
      pathway responsible for integrating multiple stimuli, Pten represents an
      important regulator of both skeletal size and bone architecture.

PMID- 17456010
TI  - Development of a combined biological and chemical process for production of
      industrial aromatics from renewable resources.
AB  - Production of industrial aromatic chemicals from renewable resources could
      provide a competitive alternative to traditional chemical synthesis routes. This
      review describes the engineering of microorganisms for the production of p
      hydroxycinnamic acid (pHCA) and p-hydroxystyrene (pHS) from glucose. The initial
      process concept was demonstrated using a tyrosine-producing Escherichia coli
      strain that overexpressed both fungal phenylalanine/tyrosine ammonia lyase (PAL)
      and bacterial pHCA decarboxylase (pdc) genes. Further development of this
      bioprocess resulted in uncoupling the pHCA and pHS production steps to mitigate
      their toxicity to the production host. The final process consists of a
      fermentation step to convert glucose to tyrosine using a tyrosine-overproducing
      E. coli strain. This step is followed by a single biotransformation reaction to
      deaminate tyrosine to pHCA through immobilized E. coli cells that overexpress the
      Rhodotorula glutinis PAL gene. Finally, chemical decarboxylation of pHCA produces
      pHS. This multifaceted approach, which integrates biology, chemistry, and
      engineering, has allowed development of an economical process at scales suitable
      for industrial applications.

PMID- 17456011
TI  - Designing sensitive and specific spaced seeds for cross-species mRNA-to-genome
      alignment.
AB  - As the demand for accurately aligning gene sequences to the genome of a related
      species grows with the sequencing of new genomes, spaced seeds emerge as a
      promising vehicle for increasing alignment sensitivity. We extend the existing
      {0, 1} match-mismatch models for sensitivity evaluation to take into account the
      compositional structure of coding sequences and ultimately produce seeds better
      suited to this particular application. Designing seeds for alignment programs,
      however, needs to balance sensitivity and specificity. We assess the effects of
      seed variations on both sensitivity and specificity in an extended model that
      incorporates transitions and differentiates among the three codon positions, and
      show that spaced seeds with transitions offer a better sensitivity-specificity
      tradeoff. Furthermore, we propose a theoretical formulation for rigorously
      assessing seed specificity, starting from Bernoulli and Markov models of the mRNA
      and genomic sequences. Within this framework, we perform the first comprehensive
      analysis of seeds to serve as a blueprint for selecting sensitive and specific
      seeds for practical applications. Our analyses show that specificity is
      relatively constant for seeds of a given weight, while sensitivity varies widely,
      with the highest values attained by seeds allowing a small (2-6) number of
      transitions.A strategy for designing seeds, therefore, is to first select the
      weight of the seed by identifying the desired sensitivity-specificity tradeoff,
      then choose the most sensitive seed(s) within that weight group. We illustrate
      our methods with the alignment of chicken coding sequences against the human
      genome assembly version HG17.

PMID- 17456012
TI  - Fast molecular shape matching using contact maps.
AB  - In this paper, we study the problem of computing the similarity of two protein
      structures by measuring their contact-map overlap. Contact-map overlap abstracts
      the problem of computing the similarity of two polygonal chains as a graph
      theoretic problem. In R3, we present the first polynomial time algorithm with any
      guarantee on the approximation ratio for the 3-dimensional problem. More
      precisely, we give an algorithm for the contact-map overlap problem with an
      approximation ratio of sigma where sigma = min{sigma(P1), sigma(P2)} <or=
      O(n(1/2)) is a decomposition parameter depending on the input polygonal chains P1
      and P2. In R2, we improve the running time of the previous best known
      approximation algorithm from O(n(6)) to O(n(3) log n) at the cost of decreasing
      the approximation ratio by half. We also give hardness results for the problem in
      three dimensions, suggesting that approximating it better than O(n(epsilon)), for
      some epsilon > 0, is hard.

PMID- 17456013
TI  - Interpreting chromosome aberration spectra.
AB  - Ionizing radiation can damage cells by breaking both strands of DNA in multiple
      locations, essentially cutting chromosomes into pieces. The cell has enzymatic
      mechanisms to repair such breaks; however, these mechanisms are imperfect and, in
      an exchange process, may produce a large-scale rearrangement of the genome,
      called a chromosome aberration. Chromosome aberrations are important in killing
      cells, during carcinogenesis, in characterizing repair/misrepair pathways, in
      retrospective radiation biodosimetry, and in a number of other ways. DNA staining
      techniques such as mFISH (multicolor fluorescent in situ hybridization) provide a
      means for analyzing aberration spectra by examining observed final patterns.
      Unfortunately, an mFISH observed final pattern often does not uniquely determine
      the underlying exchange process. Further, resolution limitations in the painting
      protocol sometimes lead to apparently incomplete final patterns. We here describe
      an algorithm for systematically finding exchange processes consistent with any
      observed final pattern. This algorithm uses aberration multigraphs, a
      mathematical formalism that links the various aspects of aberration formation. By
      applying a measure to the space of consistent multigraphs, we will show how to
      generate model-specific distributions of aberration processes from mFISH
      experimental data. The approach is implemented by software freely available over
      the internet. As a sample application, we apply these algorithms to an aberration
      data set, obtaining a distribution of exchange cycle sizes, which serves to
      measure aberration complexity. Estimating complexity, in turn, helps indicate how
      damaging the aberrations are and may facilitate identification of radiation type
      in retrospective biodosimetry.

PMID- 17456014
TI  - Phylogeny of mixture models: robustness of maximum likelihood and non
      identifiable distributions.
AB  - We address phylogenetic reconstruction when the data is generated from a mixture
      distribution. Such topics have gained considerable attention in the biological
      community with the clear evidence of heterogeneity of mutation rates. In our work
      we consider data coming from a mixture of trees which share a common topology,
      but differ in their edge weights (i.e., branch lengths). We first show the
      pitfalls of popular methods, including maximum likelihood and Markov chain Monte
      Carlo algorithms. We then determine in which evolutionary models, reconstructing
      the tree topology, under a mixture distribution, is (im)possible. We prove that
      every model whose transition matrices can be parameterized by an open set of
      multilinear polynomials, either has non-identifiable mixture distributions, in
      which case reconstruction is impossible in general, or there exist linear tests
      which identify the topology. This duality theorem, relies on our notion of linear
      tests and uses ideas from convex programming duality. Linear tests are closely
      related to linear invariants, which were first introduced by Lake, and are
      natural from an algebraic geometry perspective.

PMID- 17456015
TI  - Computing the partition function and sampling for saturated secondary structures
      of RNA, with respect to the Turner energy model.
AB  - An RNA secondary structure is saturated if no base pairs can be added without
      violating the definition of secondary structure. Here we describe a new
      algorithm, RNAsat, which for a given RNA sequence a, an integral temperature 0
      <or= T <or= 100 in degrees Celsius, and for all integers k, computes the
      Boltzmann partition function Z(k)(T)(a) = SigmaSepsilonSAT(k)(a) exp(-E(S)/RT),
      where the sum is over all saturated secondary structures of a which have exactly
      k base pairs, R is the universal gas constant and E(S) denotes the free energy
      with respect to the Turner nearest neighbor energy model. By dynamic programming,
      we compute Z(k)(T)simultaneously for all values of k in time O(n(5)) and space
      O(n(3)).Additionally, RNAsat computes the partition function Q(k)(T)(a) =
      SigmaSepsilonS(k)(a) exp(-E(S)/RT), where the sum is over all secondary
      structures of a which have k base pairs; the latter computation is performed
      simultaneously for all values of k in O(n(4)) time and O(n(3)) space. Lastly,
      using the partition function Z(k)(T) [resp. Q(k)(T)] with stochastic
      backtracking, RNAsat rigorously samples the collection of saturated secondary
      structures [resp. secondary structures] having k base pairs; for Q(k)(T) this
      provides a parametrized form of Sfold sampling (Ding and Lawrence, 2003). Using
      RNAsat, (i) we compute the ensemble free energy for saturated secondary
      structures having k base pairs, (ii) show cooperativity of the Turner model,
      (iii) demonstrate a temperature-dependent phase transition, (iv) illustrate the
      predictive advantage of RNAsat for precursor microRNA cel-mir-72 of C. elegans
      and for the pseudoknot PKB 00152 of Pseudobase (van Batenburg et al., 2001), (v)
      illustrate the RNA shapes (Giegerich et al., 2004) of sampled secondary
      structures [resp. saturated structures] having exactly k base pairs. A web server
      for RNAsat is under construction at bioinformatics.bc.edu/clotelab/RNAsat/.

PMID- 17456016
TI  - Reconstruction of ancestral genomic sequences using likelihood.
AB  - A challenging task in computational biology is the reconstruction of genomic
      sequences of extinct ancestors, given the phylogenetic tree and the sequences at
      the leafs. This task is best solved by calculating the most likely estimate of
      the ancestral sequences, along with the most likely edge lengths. We deal with
      this problem and also the variant in which the phylogenetic tree in addition to
      the ancestral sequences need to be estimated. The latter problem is known to be
      NP-hard, while the computational complexity of the former is unknown. Currently,
      all algorithms for solving these problems are heuristics without performance
      guarantees. The biological importance of these problems calls for developing
      better algorithms with guarantees of finding either optimal or approximate
      solutions. We develop approximation, fix parameter tractable (FPT), and fast
      heuristic algorithms for two variants of the problem; when the phylogenetic tree
      is known and when it is unknown. The approximation algorithm guarantees a
      solution with a log-likelihood ratio of 2 relative to the optimal solution. The
      FPT has a running time which is polynomial in the length of the sequences and
      exponential in the number of taxa. This makes it useful for calculating the
      optimal solution for small trees. Moreover, we combine the approximation
      algorithm and the FPT into an algorithm with arbitrary good approximation
      guarantee (PTAS). We tested our algorithms on both synthetic and biological data.
      In particular, we used the FPT for computing the most likely ancestral
      mitochondrial genomes of hominidae (the great apes), thereby answering an
      interesting biological question. Moreover, we show how the approximation
      algorithms find good solutions for reconstructing the ancestral genomes for a set
      of lentiviruses (relatives of HIV). Supplementary material of this work is
      available at www.nada.kth.se/~isaac/publications/aml/aml.html.

PMID- 17456017
TI  - Generalized correlation functions and their applications in selection of optimal
      multiple spaced seeds for homology search.
AB  - The Goulden-Jackson cluster method is a powerful method to calculate the
      probability of occurrences of a pattern or set of patterns in a sequence. If the
      patterns contain wildcard characters, however, the size of the connector matrix
      grows exponentially with the number of wildcards. Here we show that average
      correlation c(z) is a good predicator of hitting probability q (n), and the
      generalized correlation function c(z) can be used to approximate c(z)
      efficiently. We apply the method to the problem of optimal multiple spaced seed
      selection for homology search. We reexamine the concept of optimal sensitivity of
      spaced seeds and show that it is better to select optimal seeds based on some
      average properties, such as c(1), which is the expectation of the first hitting
      length. Higher order approximations can also be constructed easily. Tests on
      arbitrary large genomic data with multiple seeds show that the optimal multiple
      seeds selected by the methods are indeed more sensitive. The methods provide a
      theoretical background on which various empirical observations can be unified and
      further heuristic search methods can be developed.

PMID- 17456018
TI  - Penetration of nonenveloped viruses into the cytoplasm.
AB  - Although the precise mechanism by which nonenveloped viruses penetrate biological
      membranes is unclear, a more coherent understanding of this process is starting
      to emerge. To initiate membrane penetration, nonenveloped viruses engage host
      cell factors that impart conformational changes on the viral particles, resulting
      in the exposure of a hydrophobic moiety or the release of a lytic factor. The
      viruses' interactions with the limiting membrane subsequently compromise the
      bilayer integrity. This reaction presumably perforates the bilayer to enable the
      virus to cross the membrane and reach the cytosol. Valuable insights into this
      process can be gleaned from the membrane transport mechanisms of enveloped
      viruses and bacterial toxins. To identify systematically the cellular components
      that facilitate nonenveloped virus membrane penetration, sensitive assays that
      monitor the transport event directly must first be established. Moreover, higher
      resolution structures of penetration intermediates, particularly those solved in
      complex with membranes, would provide important molecular details into this
      process.

PMID- 17456019
TI  - Heart field: from mesoderm to heart tube.
AB  - In this review we discuss the major morphogenetic and regulative events that
      control myocardial progenitor cells from the time that they delaminate from the
      epiblast in the primitive streak to their differentiation into cardiomyocytes in
      the heart tube. During chick and mouse embryogenesis, myocardial progenitor cells
      go through four specific processes that are sequential but overlapping:
      specification of the cardiogenic mesoderm, determination of the bilaterally
      symmetric heart fields, patterning of the heart field, and finally cardiomyocyte
      differentiation and formation of the heart tube. We describe the morphological
      and molecular events that play a pivotal role in each of these four processes.

PMID- 17456020
TI  - Enhancement of chemotherapeutic efficacy by small molecule inhibition of NF
      kappaB and checkpoint kinases.
AB  - Apoptosis or programmed cell death is a cellular mechanism used to regulate cell
      number and eliminate damaged or mutated cells. Many chemotherapeutic agents and
      ionizing radiation induce not only apoptotic signaling pathways, but also
      survival responses such as DNA damage responses and cell cycle arrest, which
      allow for DNA repair. These survival responses determine the toxicity as well as
      the efficacy of the cancer treatment. Two main DNA damage responses include the
      activation of the anti-apoptotic transcription factor NF-kappaB and the
      activation of cell cycle checkpoint kinases. Strategies of combining
      chemotherapeutics with (a) inhibitors of NF-kappaB or (b) inhibitors of
      checkpoint kinases, may therefore enhance the efficacy of current cancer
      therapies. This review will be focused on recent progress made in combining
      traditional chemotherapeutic drugs with small molecule inhibitors of NF-kappaB
      and the checkpoint kinases, Chk1 and Chk2.

PMID- 17456021
TI  - Early-life immune insult and developmental immunotoxicity (DIT)-associated
      diseases: potential of herbal- and fungal-derived medicinals.
AB  - Developmental immunotoxicity (DIT) is increasingly recognized as a significant
      risk factor contributing to later life immune dysfunction as well chronic
      disease. In fact, recent increases in the incidence of asthma, allergic disease,
      autoimmunity and childhood infections maybe linked to problematic early life
      environmental exposures. The immune system of the non-adult is particularly
      susceptible to environmental influences whether from prenatal exposure to
      environmental toxins, maternally-administered drugs, infections or from postnatal
      exposure to toxicants, infectious agents and allergens. Additionally, adult
      exposure models of immunotoxicity have been largely ineffective in predicting DIT
      risk. DIT-induced immune dysfunction can take many forms depending upon the
      environmental factor(s) involved and the precise developmental timing of
      exposure. If one examines the spectrum of published studies, a predominant
      phenotype has emerged that includes: Th balance skewing toward Th2, suppression
      of Th1 function, regulatory T cell function alteration, T cell repertoire
      abnormalities, problematic regulation of inflammatory cell function leading to
      hyperinflammatory responses and perturbation of cytokine networks. Early-life
      immune insult can also result in damage to the neurological and cardiovascular
      systems as well as endocrine and reproductive organs. Most therapeutic approaches
      to date have addressed the disease outcomes of DIT (e.g. asthma, allergy,
      autoimmunity, infections, and cancer) rather than focusing on the underlying
      immune dysfunction that creates the increased disease risk. While identification
      and prevention of problematic early life exposures is the best protection against
      DIT, this is not always possible. Therefore, identification of potential
      therapeutic approaches to reverse the immune dysfunction in the juvenile or adult
      is needed. In this review, we consider potential phytotherapeutic candidates
      among herbal- and fungal-derived medicinals for possible postnatal correction of
      the most predominant DIT-induced immune problems.

PMID- 17456022
TI  - The ERp57/GRp58/1,25D3-MARRS receptor: multiple functional roles in diverse cell
      systems.
AB  - ERp57/GRp58 is a thiol-protein disulphide oxidoreductase and has been studied in
      many clinically relevant systems, both as a chaperone protein and as a membrane
      receptor for the steroid hormone, 1,25(OH)2D3. Our laboratory investigates
      phenomena associated with rapid, membrane-initiated signaling by steroid hormones
      synthesized from vitamin D (cholecalciferol). We have recently reported that the
      cell surface receptor for the metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3],
      which we have termed the 1,25D3-MARRS (Membrane Associated, Rapid Response
      Steroid binding) receptor, is in fact identical to ERp57/GRp58. Here we review
      the dynamic role ERp57/GRp58/1,25D3-MARRS receptor plays in a variety of cellular
      processes. Starting with its structure at the DNA and protein levels, we review
      the available literature about its role as a chaperone protein, in immune
      function through the assembly of MHC class I molecules, DNA binding, and its
      function as the 1,25D3-MARRS receptor. Finally, we present the role it may play
      in relation to important disease states. While ERp57/GR58/1,25D3-MARRS receptor
      is a pivotal protein in many cell functions, it has yet to be determined whether
      and to what extent-these phenomena are regulated by the vitamin D endocrine
      system. However, 1,25(OH)2D3 is involved in differentiation of certain cancer
      cells and in muscle function, and ERp57/1,25D3-MARRS protein has been reported to
      be involved in such processes. Thus, medicinal chemistry aimed at the 1,25D3
      MARRS receptor in lymphocytes, cancer cells, bone, intestinal epithelia, and
      kidney may add to the current therapeutic regimens for various disease states.

PMID- 17456023
TI  - The contribution of adipose tissue and adipokines to inflammation in joint
      diseases.
AB  - Adipokines are proteins produced by white adipose tissue, which is an active
      secretory organ. Regulation of immune and inflammatory responses is among the
      multiple physiological processes involving adipokines. Leptin, adiponectin and
      resistin are the most extensively studied adipokines. Leptin may promote
      inflammation by inducing Th1 phenotype development, whereas adiponectin may
      combat inflammation by reducing the production of pro-inflammatory cytokines.
      Resistin belongs to a family of proteins found in foci of inflammation, where
      they contribute to the inflammatory response. All three adipokines have been
      detected in synovial fluid from joints affected with the inflammatory disease
      rheumatoid arthritis (RA) or the degenerative disease osteoarthritis (OA). Recent
      evidence points to involvement of leptin in RA and OA and indicates that
      adiponectin and/or resistin mediate inflammation in arthritis. Thus, fat tissue
      is an active organ whose products contribute to inflammatory and degenerative
      processes underlying common joint diseases.

PMID- 17456024
TI  - New insights into aminoglycoside antibiotics and derivatives.
AB  - In the post-genome era, RNA has emerged as a valid molecular target involved in
      many biochemical pathways such as cellular protein interactions. This includes
      transcription and translation, HIV-Rev and HIV-tat proteins binding to HIV RNA
      that encode HIV genetic information. The binding of natural and synthetic
      aminoglycosides to RNA or RNA-protein complexes has been a central focus of small
      molecules-RNA recognition events, since they bind selectively to a variety of RNA
      targets. The understanding of the contribution of shape-based and charge motifs
      involved in aminoglycosides-RNA complexes gives remarkable information of the
      translational miscoding process, thereby opening new insights for drug discovery.
      This review comprises relevant information about aminoglycosides antibiotics,
      including chemical structure, molecular mechanism, structure-activity
      relationships, recent advances in aminoglycoside mimetics over the last four
      years, resistance mechanisms and structure-toxicity relationships.

PMID- 17456025
TI  - Respiratory effects of beta-adrenergic receptor blockers.
AB  - Antagonists of the beta-adrenergic receptor (beta-AR antagonists) are a
      heterogeneous class of drugs. Selected members of this class are highly
      recommended in congestive heart failure (HF) and after acute myocardial
      infarction. Hydrosolubility, half life and prevalent route of excretion define
      the pharmacokinetic profile of individual drugs, whereas the respective degree of
      affinity for beta1-AR and beta2-AR, the level of coexistent agonist properties
      and several beta-AR independent properties (e. g. antioxidant, direct
      vasodilating effect) contribute to shape the pharmacodynamic profile. Genetically
      determined differences in the response to beta-AR antagonists and, probably, age
      related changes in the neuroautonomic system are further source of variability in
      the effect of beta-AR antagonists on bronchial tone. Patients with chronic
      obstructive pulmonary disease (COPD) are theoretically at risk of worsening
      respiratory flows and symptoms caused by beta-AR antagonists prescribed for
      concurrent HF or myocardial infarction. Most of these patients, however, do not
      experience side effects, maybe because the improved haemodynamic due to beta-AR
      antagonists therapy may in turn improve the respiratory function. Occasional
      patients can develop untoward respiratory effects of beta-AR antagonists, and
      this risk is higher for those with severe COPD or active asthma. We provide some
      simple common sense rules for selecting patients with COPD or asthma that are
      suitable for beta-AR antagonists therapy while minimizing the risk of adverse
      respiratory effects.

PMID- 17456026
TI  - Pharmacological modulation of stem cell function.
AB  - The discovery of stem cells (SC) has shed new light on the understanding of
      mechanisms responsible for ischemic and degenerative disorders, and opened a new
      field for regenerative medicine. Furthermore, dysregulation of SC self-renewal
      and their transformation seem to be involved also in the development of cancer,
      suggesting that pharmacological treatment devoted to regulate SC genomic and
      phenotypic functions might represent a potential new strategy even for the
      treatment of neoplastic disorders. SC display a promiscuous set of transcription
      factors and an open chromatin structure which are required to maintain their
      multipotentiality, while they are progressively quenched during differentiation
      into specific multiple lineages. The mechanisms that govern stem cell fate
      decisions are under tight control but remain potentially alterable. Recent
      studies have shown that several currently used drugs such as colony stimulating
      factors, statins, angiotensin-II receptor antagonists/ACE-inhibitors,
      Erythropoietin, nitric oxide donors, estrogens and glitazones, have modulatory
      activity on SC functions. These drugs mostly enhance SC survival and
      mobilization. Furthermore, a series of new pharmacological agents such as the
      chemokine receptor antagonist AMD3100, glycogen synthase kinase-3 (GSK-3)
      inhibitors and histone deacetylase inhibitors (HDACi), that modulate the growth,
      differentiation and mobilization of SC, have been recently discovered and are
      currently under evaluation in both in vivo experimental models and preliminary
      clinical trials. Thus, modulation of SC properties through pharmacological
      treatment represents a new field of investigation which may lead to the
      development of novel strategies for the treatment not only of ischemic and
      degenerative disorders, but also of cancer.

PMID- 17456027
TI  - Cell type specific redox status is responsible for diverse electromagnetic field
      effects.
AB  - Epidemiologic and experimental research on the potential carcinogenic effects of
      extremely low frequency electromagnetic fields (ELF-EMF) has been performed for a
      long time. Epidemiologic studies regarding ELF-EMF-exposure have focused
      primarily on leukaemia development due to residential sources in children and
      adults, and from occupational exposure in adults, but also on other kinds of
      cancer. Genotoxic investigations of EMF have shown contradictory results, a
      biological mechanism is still lacking that can explain the link between cancer
      development and ELF-EMF-exposure. Recent laboratory research has attempted to
      show general biological effects, and such that could be related to cancer
      development and/or promotion. Metabolic processes which generate oxidants and
      antioxidants can be influenced by environmental factors, such as ELF-EMF.
      Increased ELF-EMF exposure can modify the activity of the organism by reactive
      oxygen species leading to oxidative stress. It is well established that free
      radicals can interact with DNA resulting in single strand breaks. DNA damage
      could become a site of mutation, a key step to carcinogenesis. Furthermore,
      different cell types react differently to the same stimulus, because of their
      cell type specific redox status. The modulation of cellular redox balance by the
      enhancement of oxidative intermediates, or the inhibition or reduction of
      antioxidants, is discussed in this review. An additional aspect of free radicals
      is their function to influence other illnesses such as Parkinson's and
      Alzheimer's diseases. On the other hand, modulation of antioxidants by ELF-EMF
      can lower the intracellular defence activity promoting the development of DNA
      damage. It has also been demonstrated that low levels of reactive oxygen species
      trigger intracellular signals that involve the transcription of genes and leading
      to responses including cell proliferation and apoptosis. In this review, a
      general overview is given about oxidative stress, as well as experimental studies
      are reviewed as they are related to changes in oxidant and antioxidant content
      after ELF-EMF exposure inducing different biological effects. Finally, we
      conclude from our review that modulations on the oxidant and antioxidant level
      through ELF-EMF exposure can play a causal role in cancer development.

PMID- 17456028
TI  - Chemotherapy of leishmaniasis: past, present and future.
AB  - Leishmaniasis is a parasitic disease caused by hemoflagellate, Leishmania spp.
      The parasite is transmitted by the bite of an infected female phlebotomine
      sandfly. The disease is prevalent throughout the world and in at least 88
      countries. Nearly 25 compounds are reported to have anti-leishmanial effects but
      not all are in use. The pentavalent antimony compounds have remained mainstay for
      nearly 75 years. Pentavalent antimony is a prodrug that is reduced by glutathione
      to active trivalent species catalyzed by thiol-dependent-reductase. However,
      emergence of resistance led to the use of other compounds--amphotericin B,
      pentamidine, paromomycin, allopurinol etc. Amphotericin B, an antifungal
      macrolide polyene is characterized by the hydrophilic polyhydroxyl and
      hydrophobic polyene faces on it long axis. Presently, it is the only drug with
      highest cure rate. It acts on membrane sterols resulting in parasite cell lysis.
      Its lipid formulations have been developed to minimize side effects. Other anti
      fungals like ketoconazole, fluconazole and terbinafine are found less effective.
      Recently, anticancer alkylphosphocholines have been found most effective oral
      compounds. These act as membrane synthetic ether-lipid analogues, and consist of
      alkyl chains in the lipid portions. Most promising of these are miltefosine
      (hexadecylphosphocholine), edelfosine (ET-18-OCH(3)) and ilmofosine (BM 41.440).
      However, the recent focus has been on identifying newer therapeutic targets in
      the parasite such as DNA topoisomerases. The present review describes the current
      understanding of different drugs against leishmaniasis, their chemistry, mode of
      action and the mechanism of resistance in the parasite. Future perspectives in
      the area of new anti-leishmanial drug targets are also enumerated. However, due
      to the vastness of the topic main emphasis is given on visceral leishmaniasis.

PMID- 17456029
TI  - Alginate/polymethacrylate copolymer microparticles for the intestinal delivery of
      enzymes.
AB  - Proteins administered orally must pass through the gastric environment in order
      to reach their site of absorption in the intestine. How to protect these
      exogenously administered proteins from the damaging effects of gastric acid and
      pepsin proteolytic activity, which often induce irreversible structural and
      functional alterations to the molecules, is an intriguing challenge. Another
      problem is the physical and chemical instability of proteins during some
      technological processes, which often involve the use of organic solvents or high
      temperatures. In this study we investigated the use of alginate microparticles
      containing one of two enzymes, an enteric polymer and a lyoprotectant for the
      intestinal delivery of proteins. The two enzymes tested in this protein delivery
      system were lactate dehydrogenase and alpha-amylase: the former was chosen
      because of its sensitivity to denaturation, the latter for its relevance in
      nutrition and medicine. A sodium alginate aqueous solution containing the enteric
      polymer, a lyoprotectant and the enzyme was either extruded or sprayed into a
      calcium chloride solution, with the resultant formation of beads and microspheres
      which were freeze-dried. About 90% of the enzyme activity was maintained during
      the process of loading the proteins into the microparticles and the subsequent
      freeze-drying process. The stability of the encapsulated enzyme in an acid medium
      and the enzymatic activity in an intestinal environment were then investigated by
      a dissolution test. This consisted of exposing the microparticles to simulated
      gastric fluid (pH 1.2) for 2 hours and to simulated intestinal fluid (pH 7.5+/
      0.1) for 1 hour. The morphology of the microparticles did not change in the acid
      environment, whereas they completely dissolved within 3 min in the simulated
      intestinal fluid. Residual enzymatic activity after the test remained
      satisfactory for both enzymes. In conclusion, these microparticle systems offer
      promise for applications in human and veterinary medicine as well as in human and
      animal nutrition.

PMID- 17456030
TI  - Evaluation of cell tolerability of a series of lipoamino acids using biological
      membranes and a biomembrane model.
AB  - The interaction of a series of amphiphilic 2-alkyl aminoacids (lipoamino acids,
      LAAs) with different cell cultures and biomembrane models was investigated. LAAs
      can be useful promoieties to modify the physico-chemical properties of many
      drugs, and in particular their lipophilicity. Tests were performed in vitro on
      mammalian cells (murine astrocytes) and human red blood cells (haemolysis), and
      in vivo on rabbit eye as alternative models to assess the tolerability or the
      potential damaging effects of these compounds on different biological systems.
      The mode of interaction of LAAs with pure phospholipid multilamellar liposomes,
      taken as a biomembrane model, was also analysed by differential scanning
      calorimetry experiments. Different tolerability/toxicity patterns were obtained
      in the various models; in particular, the most lipophilic terms of the series,
      methyl 2-aminohexadecanoate (LAA16), displayed haemolytic activity and toxicity
      for mouse astrocyte cultures. A specific assay confirmed that LAA16 acted at
      level of cell membranes, while neither any damaging effects on nucleus or
      apoptotic induction were observed. The shorter-chain LAAs and the tetradecyl
      homologue (LAA14) showed the best compatibility with the various cell models.

PMID- 17456031
TI  - Microsponge delivery system.
AB  - Microsponges are polymeric delivery systems consisting of porous microspheres
      having a size range in between 5 to 300 microm depending upon the degree of
      smoothness or after feel required for the end formulations. Microsponge Delivery
      System MDS is a unique technology for controlled delivery of drug. The present
      review introduces Microsponge technology along with its synthesis,
      characterization, programmable parameters and release mechanism of MDS. Wide
      ranges of applications are also suggested to develop drug or cosmetic products
      with enhanced safety and efficacy. MDS can provide increased efficacy for
      topically active agents with enhanced safety, extended product stability and
      improved aesthetic properties in an efficient and novel manner.

PMID- 17456032
TI  - Formulation considerations of gadolinium lipid nanoemulsion for intravenous
      delivery to tumors in neutron-capture therapy.
AB  - The effects of the formulation and particle composition of gadolinium (Gd)
      containing lipid nanoemulsion (Gd-nanoLE) on the biodistribution of Gd after its
      intravenous (IV) injection in D(1)-179 melanoma-bearing hamsters were evaluated
      for its application in cancer neutron-capture therapy. Gd-nanoLEs whose particles
      had an oily core (soybean oil, ethyl oleate, lipiodol, or triolein) and a surface
      layer of hydrogenated phosphatidylcholine, gadolinium-diethyl
      enetriaminepentaacetic acid-distearylamide, and a cosurfactant (Myrj 53, Brij
      700, or HCO-60) were prepared by a thin-layer hydration-sonication method.
      Biodistribution data revealed that Brij 700 and HCO-60 prolonged the retention of
      Gd in the blood and enhanced its accumulation in tumors. Among the core
      components employed, soybean oil yielded the highest Gd concentration in the
      blood and tumor and the lowest in the liver and spleen. Gd-nanoLEs with a Gd
      content of 1.5-4.5 mg/ml could be formulated by using HCO-60 and soybean oil at a
      constant oil-to-water ratio, and by enriching Gd in the surface layer with the
      particle size maintained below 100 nm. When each Gd-nanoLE was IV injected once
      or twice at a 24-h interval, the Gd concentration in the tumor correlated well
      with the total dose of Gd, and it reached a maximum of 189 microg/g wet tumor.
      This maximum Gd level was greater than the limit required for significantly
      suppressing tumor growth in neutron-capture therapy.

PMID- 17456033
TI  - Recent advances in protein and peptide drug delivery systems.
AB  - Delivery of therapeutic proteins/peptides has received a considerable amount of
      attention over the last 10 years, but there are number of limitations to oral
      delivery of proteins. The barriers to peptide bioavailability after oral
      administration are intestinal membrane permeability, size, intestinal and hepatic
      metabolism and lastly solubility. A number of approaches have been used to
      overcome these limitations. Poor membrane permeabilities of hydrophilic peptides
      might be overcome by structurally modifying the compound, thus increasing their
      membrane partition characteristics and their affinity for carrier proteins.
      Another approach is site specific delivery of the peptides to the most permeable
      part of the intestine. Metabolism (hepatic and intestinal) of peptides might be
      controlled by co-administration of competitive enzyme inhibitors, structural
      modifications and administration of the compound as well as absorbed prodrug that
      is converted into therapeutically active agent after its absorption. Various
      delivery systems like prolease technology, nano-particulate and microparticulate
      delivery system, mucoadhesive delivery of peptides and microspheres have been
      developed for the delivery of proteins and peptides. Non-conventional delivery
      systems for proteins are biodegradable and non-biodegradable systems. Besides
      these, some other approaches for protein and peptide delivery are vector mediated
      delivery of proteins using adenovirus, macroflux transdermal patches, pulmonary
      delivery of proteins, delivery of proteins and peptides across blood brain
      barrier.

PMID- 17456034
TI  - Microsphere based improved sunscreen formulation of ethylhexyl methoxycinnamate.
AB  - Polymethylmethacrylate (PMMA) microspheres of ethylhexyl methoxycinnamate (EHM)
      were prepared by emulsion solvent evaporation method to improve its
      photostability and effectiveness as sunscreening agent. Process parameters like
      stirring speed and aqueous polyvinyl alcohol (PVA) concentration were analyzed in
      order to optimize the formulations. Shape and surface morphology of the
      microspheres were examined using scanning electron microscopy. Particle size of
      the microspheres was determined using laser diffraction particle size analyzer.
      The PMMA microspheres of EHM were incorporated in water-removable cream base. The
      in vitro drug release of EHM in pH 7.4 was performed using dialysis membrane.
      Thin layer chromatography was performed to determine photostability of EHM inside
      the microspheres. The formulations were evaluated for sun protection factor (SPF)
      and minimum erythema dose (MED) in albino rats. Cream base formulation containing
      microspheres prepared using EHM:PMMA in ratio of 1:3 (C(3)) showed slowest drug
      (EHM) release and those prepared with EHM: PMMA in ratio of 1:1 showed fastest
      release. The cream base formulations containing EHM loaded microspheres had shown
      better SPF (more than 16.0) as compared to formulation C(d) that contained 3%
      free EHM as sunscreen agent and showed SPF 4.66. These studies revealed that the
      incorporation of EHM loaded PMMA microspheres into cream base had greatly
      increased the efficacy of sunscreen formulation approximately four times.
      Further, photostability was also shown to be improved in PMMA microspheres.

PMID- 17456035
TI  - RNAi silencing in mouse models of neurodegenerative diseases.
AB  - RNA interference (RNAi) has emerged as a potential therapeutic approach for
      neurodegenerative diseases, particularly those associated with autosomal dominant
      patterns of inheritance. In proof of concept experiments, several groups have
      demonstrated efficacy of using viral vectors expressing short hairpin RNA (shRNA)
      directed against therapeutically relevant genes in mouse models of
      neurodegenerative diseases, including spinocerebellar ataxia, Amyotrophic Lateral
      Sclerosis, Huntington's Disease and amyloidosis (a pathological aspect of
      Alzheimer's Disease). Although viral-based RNAi has limitations that most likely
      will preclude its usage in humans, a few recent developments underscore the
      potential of non-viral-based delivery of relevant RNAi as therapeutics for
      neurodegenerative diseases. Here, I will review the recent literature on
      effectiveness of RNAi as a therapeutic strategy in mouse models of
      neurodegenerative diseases.

PMID- 17456036
TI  - Convection enhanced drug delivery of novel therapeutic agents to malignant brain
      tumors.
AB  - In spite of conventional treatment modalities which include surgery,
      chemotherapy, and radiotherapy, the survival rates for patients with malignant
      gliomas remain disappointing. Successful treatment has been limited by
      difficulties in delivering therapeutic agents to the central nervous system
      (CNS). Specifically, drug penetration of the blood brain barrier (BBB) poses a
      unique and challenging problem in glioma therapy. Recently, however, promising
      techniques have emerged to circumvent this problem. One such advancement is
      convection-enhanced delivery (CED). This method was originally introduced and
      refined in the early 1990s by researchers at the National Institute of Health
      (NIH) and involves drug infusion under high pressure using intracranial
      catheters. CED allows for delivery of high concentrations of therapeutic agents
      directly into brain tumors and surrounding parenchyma. This method eludes the BBB
      and allows the use of regional drug therapy, while at the same time limiting
      systemic toxicity. In the present article, we review both the pre-clinical and
      clinical studies concerning CED. We also discuss future directions and the
      potential impact of this modality on the treatment of malignant gliomas.

PMID- 17456038
TI  - Snake venom phospholipase A2 inhibitors: medicinal chemistry and therapeutic
      potential.
AB  - Phospholipases A2 (PLA2s) are commonly found in snake venoms from Viperidae,
      Hydrophidae and Elaphidae families and have been extensively studied due to their
      pharmacological and physiopathological effects in living organisms. This article
      reports a review on natural and artificial inhibitors of enzymatic, toxic and
      pharmacological effects induced by snake venom PLA2s. These inhibitors act on
      PLA2s through different mechanisms, most of them still not completely understood,
      including binding to specific domains, denaturation, modification of specific
      amino acid residues and others. Several substances have been evaluated regarding
      their effects against snake venoms and isolated toxins, including plant extracts
      and compounds from marine animals, mammals and snakes serum plasma, in addition
      to poly or monoclonal antibodies and several synthetic molecules. Research
      involving these inhibitors may be useful to understand the mechanism of action of
      PLA2s and their role in envenomations caused by snake bite. Furthermore, the
      biotechnological potential of PLA2 inhibitors may provide therapeutic molecular
      models with antiophidian activity to supplement the conventional serum therapy
      against these multifunctional enzymes.

PMID- 17456039
TI  - Structural elements of ligand recognition site in secretory phospho-lipase A2 and
      structure-based design of specific inhibitors.
AB  - Phospholipases A2 (phosphotide 2-acylhydrolases, PLA2s, EC 3.1.1.4) are widely
      distributed enzymes in the animal world. They catalyze the hydrolysis of the sn-2
      acyl ester linkage of phospholipids, producing fatty acids and lysophospholipids.
      The mammalian type II secreted phospholipase A2 (PLA2-II) is one of the most
      extensively studied member of low molecular weight (13-18 kDa) PLA2s. PLA2-II
      contains 120-125 amino acid residues and seven disulphide bridges. The important
      features of overall structure of PLA2-II contain an N-terminal helix, H1
      (residues: 2-12), an external loop (residues: 14-23), a calcium binding loop
      (Ca2+-loop, residues: 25-35), a second alpha-helix, H2 (residues: 40-55), a short
      two stranded anti-parallel beta-sheet referred to as beta-wing (residues: 75-84),
      a third alpha-helix, H3 (residues: 90-108) which is antiparallel to H2 and two
      single helical turns, SH4 (residues: 114-117) and SH5 (residues: 121-125). The
      three-dimensional structure of PLA2-II has defined a conserved active site within
      a hydrophobic channel lined by invariant hydrophobic residues. The active site
      residues His48, Asp49, Tyr52 and Asp99 are directly connected to the channel. An
      important water molecule that bridges His48 and Asp49 through hydrogen bonds is a
      part of catalytic network. Based on the structures of various complexes of group
      II PLA2, the ligand-recognition site has been divided into six subsites
      consisting of residues 2-10 (subsite 1), residues 17-23 (subsite 2), residues 28
      32 (subsite 3), residues 48-52 (subsite 4), residues 68-70 (subsite 5) and
      residues 98-106 (subsite 6). It is observed that most of the currently available
      ligands saturate only part of the ligand-recognition site leaving a wide scope to
      improve the ligand complementarity. Naturally, the ligands that interact with the
      largest number of subsites would also correspond to the maximum affinity.
      Therefore, for the design of potent inhibitors of PLA2, the stereochemical
      knowledge of the binding site as well as their potential to interact with ligands
      must be known so as to make the structure-based ligand design successful.

PMID- 17456040
TI  - PLA2 mediated arachidonate free radicals: PLA2 inhibition and neutralization of
      free radicals by anti-oxidants--a new role as anti-inflammatory molecule.
AB  - PLA2 enzyme catalyses the hydrolysis of cellular phospholipids at the sn-2
      position to liberate arachidonic acid and lysophospholipid to generate a family
      of pro-inflammatory eicosanoids and platelet activating factor. The generation of
      pro-inflammatory eicosanoids involves a series of free radical intermediates with
      simultaneous release of reactive oxygen species (superoxide and hydroxyl
      radicals). Reactive oxygen species formed during arachidonic acid metabolism
      generates lipid peroxides and the cytotoxic products such as 4-hydroxy nonenal
      and acrolein, which induces cellular damage. Thus PLA2 catalyzes the rate
      limiting step in the production of pro-inflammatory eicosanoids and free
      radicals. These peroxides and reactive oxygen species in turn activates PLA2
      enzyme and further attenuates the inflammatory process. Therefore scavenging
      these free radicals and inhibition of PLA2 enzyme simultaneously by a single
      molecule such as antioxidants is of great therapeutic relevance for the
      development of anti-inflammatory molecules. PLA2 enzymes have been classified
      into calcium dependent cPLA2 and sPLA2 and calcium independent iPLA2 forms. In
      several inflammatory diseases sPLA2 group IIA is the most abundant isoform
      identified. This isoform is therefore targeted for the development of anti
      inflammatory molecules. Many secondary metabolites from plants and marine sponges
      exhibit both anti-inflammatory and antioxidant properties. Some of them include
      flavonoids, terpenes and alkaloids. But in terms of PLA2 inhibition and
      antioxidant activity, the structural aspects of flavonoids are well studied
      rather than terpenes and alkaloids. In this line, molecules having both anti
      oxidant and PLA2 inhibitions are reviewed. A single molecule with dual activities
      may prove to be a powerful anti-inflammatory drug.

PMID- 17456041
TI  - Structural biology of recombinant bovine pancreatic phospholipase A2 and its
      inhibitor complexes.
AB  - The enzyme phospholipase A2 catalyzes the cleavage of the sn-2 acyl ester bond of
      phospholipids, leading to the production of free fatty acids and
      lysophospholipids, which leads to many inflammatory disorders. In view of its
      pharmaceutical interest, three phospholipase A2 + inhibitor (namely, (i) L-1-O
      octyl-2-heptylphosphonyl-sn-glycero-3-phosphoethanolamine, Transition State
      Analogue, (ii) 1-Hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol, MJ33
      and (iii) p-methoxybenzoic acid, anisic acid) complex structures have already
      been solved and analysed, using the data obtained from X-ray diffraction. These
      structures provide insight on the mode of binding of the inhibitor molecules at
      the active site of phospholipase A2. The knowledge of the active site geometry in
      these inhibitor bound structures, yield valuable information in the design of
      more useful therapeutic agents. This report reviews only the inhibitor bound
      recombinant bovine pancreatic phospholipase A2 structures solved using X-ray
      crystallography.

PMID- 17456042
TI  - Chemistry and structural evaluation of different phospholipase A2 inhibitors in
      arachidonic acid pathway mediated inflammation and snake venom toxicity.
AB  - PLA2 inhibitors specific to Group I and II PLA2 isoforms are therapeutically
      important as anti-inflammatory molecules and against venom toxicity. From various
      natural sources diversified molecules with PLA2 inhibition and concomitant
      neutralization of inflammatory reactions and venom toxicity were characterized.
      Using these molecules, lead compounds are generated in several laboratories.
      Analogues of lead molecules were generated by substituting different types of
      functional groups in order to obtain a molecule with optimal PLA2 inhibition. The
      lead molecules characterized as PLA2 inhibitors are indoles, azetidinones,
      piperazines, isoxazolidines, isoxazolines, diazepinones, acenaphthenes and
      several substrate analogues. The lead optimization involves relative
      hydrophobicity and substitution of functional groups, such as electron
      withdrawing or donating. Many such groups are placed on hydrophobic moiety and
      their positional bioisosters are characterized. Among these analogue piperazine
      derivatives on optimization with respect to hydrophobicity and electronegativity
      showed inhibition at nanomolar levels. Structural analysis of many lead molecules
      indicated that a PLA2 inhibitor should have both hydrophobic moiety and polar
      functional groups. Each lead molecule requires optimization in this regard for
      effective inhibition.

PMID- 17456043
TI  - Group IIA secretory PLA2 inhibition by ursolic acid: a potent anti-inflammatory
      molecule.
AB  - Ursolic acid (3beta-hydroxy-urs-12-en-28-oic acid) isolated from many medicinal
      plants has diverse pharmacologically important properties, including strong anti
      inflammatory activity. However its interaction with pro-inflammatory PLA2 is not
      known. Ursolic acid inhibited secretory PLA2 (sPLA2) enzymes purified from Vipera
      russelli, Naja naja venom and human pleural fluid and synovial fluid. IC50 values
      determined for these enzymes ranged from 12 to 18 microM. Group II secretory PLA2
      from both venoms & human inflammatory source were found to be sensitive to
      inhibition in comparison with group I cobra venom sPLA2. Variation in Ca2+
      concentration from 2.5-15 mM did not alter the level of inhibition. Similarly
      sPLA2 inhibition by ursolic acid is independent of substrate concentration.
      Ursolic acid interacts with purified venom sPLA2 enzymes and enhances relative
      fluorescence intensity in a dose dependent manner. In the presence of ursolic
      acid apparent shift in the far UV-CD spectra of sPLA2 was observed, indicating a
      direct interaction with the enzyme and formation of enzyme-ursolic acid complex.
      This complex results in irreversible inhibition of sPLA2 as evident by dialysis
      study. Inhibition of sPLA2 induced mouse paw edema and indirect hemolytic
      activity confirmed its sPLA2 inhibitory activity in vivo and in situ
      respectively. These studies revealed that the strong anti-inflammatory activity
      of ursolic acid is by inhibiting sPLA2 enzymes.

PMID- 17456044
TI  - Synthesis and evaluation of tricyclic dipyrido diazepinone derivatives as
      inhibitors of secretory phospholipase A2 with anti-inflammatory activity.
AB  - A series of tricyclic dipyrido diazepinone derivatives 6(a-f) bearing different
      substituents at the tenth position of diazepinone ring were designed and are
      characterized by 1H NMR, FTIR and X-Ray crystallography studies. The synthesised
      derivatives are tested in-vitro phospholipase A2 (PLA2) enzyme inhibitory
      activity and in-vivo anti-inflammatory activity against purified group I and
      group II PLA2 enzymes from the snake venom and human pleural fluid. Compounds
      bearing aromatic ring with different substituents at different positions shown
      varied specificity. The 6f derivative with strong electron withdrawing nitro (
      NO2) and trifluoromethyl (-CF3) groups at ortho and para positions respectively
      shown greater inhibitory activity. Inhibitory effect of the compound appeared to
      be direct interaction with active site and likely competes with substrates as
      supported by substrate dependent and calcium independent assays. The IC50 value
      of potent PLA2 inhibitor 6f was 22.1 microM and showed similar potency in the
      neutralization of in vivo PLA2 induced mouse paw edema and hemolytic activity.

PMID- 17456045
TI  - Engineering the substrate and inhibitor specificities of human coagulation Factor
      VIIa.
AB  - The remarkably high specificity of the coagulation proteases towards
      macromolecular substrates is provided by numerous interactions involving the
      catalytic groove and remote exosites. For FVIIa [activated FVII (Factor VII)],
      the principal initiator of coagulation via the extrinsic pathway, several
      exosites have been identified, whereas only little is known about the specificity
      dictated by the active-site architecture. In the present study, we have profiled
      the primary P4-P1 substrate specificity of FVIIa using positional scanning
      substrate combinatorial libraries and evaluated the role of the selective active
      site in defining specificity. Being a trypsin-like serine protease, FVIIa had P1
      specificity exclusively towards arginine and lysine residues. In the S2 pocket,
      threonine, leucine, phenylalanine and valine residues were the most preferred
      amino acids. Both S3 and S4 appeared to be rather promiscuous, however, with some
      preference for aromatic amino acids at both positions. Interestingly, a
      significant degree of interdependence between the S3 and S4 was observed and, as
      a consequence, the optimal substrate for FVIIa could not be derived directly from
      a subsite-directed specificity screen. To evaluate the role of the active-site
      residues in defining specificity, a series of mutants of FVIIa were prepared at
      position 239 (position 99 in chymotrypsin), which is considered to be one of the
      most important residues for determining P2 specificity of the trypsin family
      members. This was confirmed for FVIIa by marked changes in primary substrate
      specificity and decreased rates of antithrombin III inhibition. Interestingly,
      these changes do not necessarily coincide with an altered ability to activate
      Factor X, demonstrating that inhibitor and macromolecular substrate selectivity
      may be engineered separately.

PMID- 17456046
TI  - PIASy controls ubiquitination-dependent proteasomal degradation of Ets-1.
AB  - The ETS transcription factor Ets-1 (E26 transformation-specific-1) plays a
      critical role in many physiological processes including angiogenesis,
      haematopoietic development and tumour progression. Its activity can be regulated
      by post-translational modifications, such as phosphorylation. Recently, we showed
      that Ets-1 is a target for SUMO (small ubiquitin-like modifier) modification and
      that PIASy [protein inhibitor of activated STAT (signal transducer and activator
      of transcription) Y], a specific SUMO-E3 ligase for Ets-1, represses Ets-1
      dependent transcription. In the present study, we demonstrated that Ets-1 is
      degraded by the proteasome and that overexpression of PIASy increased the
      stability of endogenous and ectopically expressed Ets-1 protein by preventing
      proteasomal degradation. Moreover, knockdown of the endogenous PIASy expression
      by RNA interference reduced the protein level of endogenous Ets-1. The proteasome
      inhibitor MG132 reversed this effect. Deletion analysis showed that the TAD
      (transcriptional activation domain), which has been identified as the interaction
      domain with PIASy, was also required for Ets-1 ubiquitination and proteasomal
      degradation. However, the Ets-1 stabilization by PIASy was not due to reduced
      ubiquitination of Ets-1. Our results suggested that PIASy controls Ets-1
      function, at least in part, by inhibiting Ets-1 protein turnover via the
      ubiquitin-proteasome system.

PMID- 17456047
TI  - Regulation of apoptosis signal-regulating kinase 1 by protein phosphatase
      2Cepsilon.
AB  - ASK1 (apoptosis signal-regulating kinase 1), a MKKK (mitogen-activated protein
      kinase kinase kinase), is activated in response to cytotoxic stresses, such as
      H2O2 and TNFalpha (tumour necrosis factor alpha). ASK1 induction initiates a
      signalling cascade leading to apoptosis. After exposure of cells to H2O2, ASK1 is
      transiently activated by autophosphorylation at Thr845. The protein then
      associates with PP5 (protein serine/threonine phosphatase 5), which inactivates
      ASK1 by dephosphorylation of Thr845. Although this feedback regulation mechanism
      has been elucidated, it remains unclear how ASK1 is maintained in the
      dephosphorylated state under non-stressed conditions. In the present study, we
      have examined the possible role of PP2Cepsilon (protein phosphatase 2Cepsilon), a
      member of PP2C family, in the regulation of ASK1 signalling. Following expression
      in HEK-293 cells (human embryonic kidney cells), wild-type PP2Cepsilon inhibited
      ASK1-induced activation of an AP-1 (activator protein 1) reporter gene.
      Conversely, a dominant-negative PP2Cepsilon mutant enhanced AP-1 activity.
      Exogenous PP2Cepsilon associated with exogenous ASK1 in HEK-293 cells under non
      stressed conditions, inactivating ASK1 by decreasing Thr845 phosphorylation. The
      association of endogenous PP2Cepsilon and ASK1 was also observed in mouse brain
      extracts. PP2Cepsilon directly dephosphorylated ASK1 at Thr845 in vitro. In
      contrast with PP5, PP2Cepsilon transiently dissociated from ASK1 within cells
      upon H2O2 treatment. These results suggest that PP2Cepsilon maintains ASK1 in an
      inactive state by dephosphorylation in quiescent cells, supporting the
      possibility that PP2Cepsilon and PP5 play different roles in H2O2-induced
      regulation of ASK1 activity.

PMID- 17456048
TI  - Mechanism of short-term ERK activation by electromagnetic fields at mobile phone
      frequencies.
AB  - The exposure to non-thermal microwave electromagnetic fields generated by mobile
      phones affects the expression of many proteins. This effect on transcription and
      protein stability can be mediated by the MAPK (mitogen-activated protein kinase)
      cascades, which serve as central signalling pathways and govern essentially all
      stimulated cellular processes. Indeed, long-term exposure of cells to mobile
      phone irradiation results in the activation of p38 as well as the ERK
      (extracellular-signal-regulated kinase) MAPKs. In the present study, we have
      studied the immediate effect of irradiation on the MAPK cascades, and found that
      ERKs, but not stress-related MAPKs, are rapidly activated in response to various
      frequencies and intensities. Using signalling inhibitors, we delineated the
      mechanism that is involved in this activation. We found that the first step is
      mediated in the plasma membrane by NADH oxidase, which rapidly generates ROS
      (reactive oxygen species). These ROS then directly stimulate MMPs (matrix
      metalloproteinases) and allow them to cleave and release Hb-EGF [heparin-binding
      EGF (epidermal growth factor)]. This secreted factor activates the EGF receptor,
      which in turn further activates the ERK cascade. Thus this study demonstrates for
      the first time a detailed molecular mechanism by which electromagnetic
      irradiation from mobile phones induces the activation of the ERK cascade and
      thereby induces transcription and other cellular processes.

PMID- 17456049
TI  - Catalytic mechanism of the glutathione peroxidase-type tryparedoxin peroxidase of
      Trypanosoma brucei.
AB  - Trypanosoma brucei, the causative agent of African sleeping sickness, encodes
      three nearly identical genes for cysteine-homologues of the selenocysteine
      containing glutathione peroxidases. The enzymes, which are essential for the
      parasites, lack glutathione peroxidase activity but catalyse the
      trypanothione/Tpx (tryparedoxin)-dependent reduction of hydroperoxides. Cys47,
      Gln82 and Trp137 correspond to the selenocysteine, glutamine and tryptophan
      catalytic triad of the mammalian selenoenzymes. Site-directed mutagenesis
      revealed that Cys47 and Gln82 are essential. A glycine mutant of Trp137 had 13%
      of wild-type activity, which suggests that the aromatic residue may play a
      structural role but is not directly involved in catalysis. Cys95, which is
      conserved in related yeast and plant proteins but not in the mammalian
      selenoenzymes, proved to be essential as well. In contrast, replacement of the
      highly conserved Cys76 by a serine residue resulted in a fully active enzyme
      species and its role remains unknown. Thr50, proposed to stabilize the thiolate
      anion at Cys47, is also not essential for catalysis. Treatment of the C76S/C95S
      but not of the C47S/C76S double mutant with H2O2 induced formation of a sulfinic
      acid and covalent homodimers in accordance with Cys47 being the peroxidative
      active site thiol. In the wild-type peroxidase, these oxidations are prevented by
      formation of an intramolecular disulfide bridge between Cys47 and Cys95. As shown
      by MS, regeneration of the reduced enzyme by Tpx involves a transient mixed
      disulfide between Cys95 of the peroxidase and Cys40 of Tpx. The catalytic
      mechanism of the Tpx peroxidase resembles that of atypical 2-Cys-peroxiredoxins
      but is distinct from that of the selenoenzymes.

PMID- 17456051
TI  - Purpura fulminans in paroxysmal nocturnal haemoglobinuria.

PMID- 17456052
TI  - The CXCR4 chemokine receptor in acute and chronic leukaemia: a marrow homing
      receptor and potential therapeutic target.
AB  - Chemokine (C-X-C motif) receptor 4 (CXCR4) is essential for homing and
      maintenance of haematopoietic stem cells in distinct stromal cell niches within
      the marrow. Chemotactic responsiveness of haematopoietic stem cells is restricted
      to the ligand for CXCR4, stromal cell-derived factor-1 (SDF-1/CXCL12), which is
      constitutively secreted by marrow stromal cells. Myeloid and lymphoid leukaemia
      cells also express CXCR4 that induces leukaemia cell chemotaxis and migration
      beneath marrow stromal cells. CXCR4 expression levels have a major prognostic
      impact in acute myeloid leukaemia. There is growing in vitro and in vivo evidence
      that CXCR4 expression by leukaemia cells allows for homing and their retention
      within the marrow. As such, leukaemia cells appear to utilise CXCR4 to access
      niches that are normally restricted to progenitor cells, and thereby reside in a
      microenvironment that favours their growth and survival. CXCR4- and integrin
      mediated contact between leukaemia cells and stromal cells protects leukaemia
      cells from spontaneous and chemotherapy-induced cell death and therefore may
      represent a mechanism to explain minimal residual disease and subsequent relapses
      commonly seen in the treatment of these diseases. This review summarises our
      current knowledge regarding the importance of CXCR4 in acute and chronic
      leukaemia, discusses the importance of CXCR4 detection by flow cytometry in the
      diagnostic workup of leukaemia patients, and introduces the potential role of
      CXCR4-targeting compounds for the treatment of leukaemia patients.

PMID- 17456053
TI  - The lymphoid cell surface receptor NTB-A: a novel monoclonal antibody target for
      leukaemia and lymphoma therapeutics.
AB  - NTB-A is a CD2-related cell surface protein expressed primarily on lymphoid cells
      including B-lymphocytes from chronic lymphocytic leukaemia (CLL) and lymphoma
      patients. We have generated a series of monoclonal antibodies (mAbs) against NTB
      A and assessed their therapeutic potential for CLL. Selective mAbs to NTB-A were
      further tested in functional complement-dependent cytotoxicity (CDC) and antibody
      dependent cellular cytotoxicty (ADCC) assays in cell lines and B lymphocytes
      freshly isolated from CLL patients. While lower levels of NTB-A were detected in
      T and natural killer (NK) cells, CDC activity was demonstrated primarily in B
      cells isolated from CLL patients and B lymphoma cell lines. Knockdown of NTB-A by
      small interfering RNA in target cells results in lower cytotoxicity,
      demonstrating the specificity of the mAbs. Furthermore, anti NTB-A mAbs
      demonstrated anti-tumour activity against CA46 human lymphoma xenografts in nude
      mice and against systemically disseminated Raji human lymphoma cells in severe
      combined immunodeficient mice. Taken together, these results demonstrate NTB-A as
      a potential new target for immunotherapy of leukaemia and lymphomas.

PMID- 17456054
TI  - Identification of novel molecular prognostic markers for paediatric T-cell acute
      lymphoblastic leukaemia.
AB  - In the last four decades the survival of patients with newly diagnosed childhood
      T-cell acute lymphoblastic leukaemia (T-ALL) has improved dramatically. In sharp
      contrast, relapsed T-ALL continues to confer a dismal prognosis. We sought to
      determine if gene expression profiling could uncover a signature of outcome for
      children with T-ALL. Using 12 patient specimens obtained before therapy started,
      we examined the gene expression profile by oligonucleotide microarrays. We
      identified three genes, CFLAR, NOTCH2 and BTG3, whose expression at the time of
      diagnosis accurately distinguished the patients according to disease outcome.
      These genes are involved in the regulation of apoptosis and cellular
      proliferation. The prognostic value of the three predictive genes was assessed in
      an independent cohort of 25 paediatric T-ALL patients using quantitative real
      time reverse transcription polymerase chain reaction. Patients assigned to the
      adverse outcome group had a significantly higher cumulative incidence of relapse
      compared with patients assigned to the favourable outcome group (46% vs. 8%, P =
      0.029). Five-year overall survival was also significantly worse in the patients
      assigned to the adverse outcome group (P = 0.0039). The independent influence of
      the 3-gene predictor was confirmed by multivariate analysis. Our study provides
      proof of principle that genome-wide expression profiling can detect novel
      molecular prognostic markers in paediatric T-ALL.

PMID- 17456055
TI  - Loss-of-function JAK3 mutations in TMD and AMKL of Down syndrome.
AB  - Acquired mutations activating Janus kinase 3 (jak3) have been reported in Down
      syndrome (DS) and non-DS patients with acute megakaryoblastic leukaemia (AMKL).
      This highlighted jak3-activation as an important event in the pathogenesis of
      AMKL, and predicted inhibitors of jak3 as conceptual therapeutics for AMKL. Of 16
      DS-transient myeloproliferative disorder (TMD)/AMKL patients tested, seven showed
      JAK3 mutations. Three mutations deleted the kinase (JH1) domain, abolishing the
      main function of jak3. Another patient displayed a mutation identical to a
      previously reported inherited loss-of-function causing severe combined
      immunodeficiency. Our data suggest that both gain-, and loss-of function
      mutations of jak3 can be acquired in DS-TMD/AMKL.

PMID- 17456056
TI  - Loss of bHLH transcription factor E2A activity in primary effusion lymphoma
      confers resistance to apoptosis.
AB  - Similar to classical Hodgkin lymphoma (HL) tumour cells, primary effusion
      lymphoma (PEL) originates from mature B cells but displays a non-B cell
      phenotype, the mechanisms and consequences of which are not yet understood. This
      study showed that PEL lacked DNA binding activity of the B cell-determining
      transcription factors E2A, EBF and Pax5. PEL overexpressed the E2A antagonists
      ABF-1 and Id2, which have been described to block the B-cell differentiation
      program in classical HL. However, in contrast to HL cells, B lineage
      inappropriate genes were not similarly upregulated in PEL, and reconstitution of
      B cell-specific E2A homodimer activity in PEL induced apoptosis. These data
      demonstrate that lineage infidelity in PEL is not as pronounced as in HL, and
      that the loss of the B cell-specific transcription factor E2A in PEL is
      implicated in apoptosis protection.

PMID- 17456057
TI  - Delayed redistribution of CD27, CD40 and CD80 positive B cells and the impaired
      in vitro immunoglobulin production in patients with non-Hodgkin lymphoma after
      rituximab treatment as an adjuvant to autologous stem cell transplantation.
AB  - Recent studies have indicated that patients who received rituximab as an adjuvant
      to stem cell transplantation (SCT) demonstrated an increased risk of developing
      severe hypogammaglobulinaemia, which was found to be a result of delayed recovery
      of CD27 positive memory B cells and impaired isotype expression. It appears that
      rituximab influences both the quantity and quality of B-cell redistribution.
      Precisely how the B-cell repertoire regenerates after anti-CD20-mediated
      transient B-cell depletion in patients with non-Hodgkin lymphoma (NHL) remains to
      be elucidated. This study performed a phenotypical analysis of B cells in 17 NHL
      patients who received rituximab as an adjuvant to autologous SCT. The median
      period after final administration of rituximab was 36 months (range, 12-43
      months). Surface antigen expression of CD27, CD40 and CD80 in NHL patients was
      statistically significantly different from healthy controls (n = 14). Moreover, B
      cells from NHL patients showed significantly impaired IgG and IgA production upon
      engagement of surface immunoglobulin receptors in the presence of interleukin
      (IL)-2, IL-10 and CD40 ligand in comparison with samples from healthy controls.
      The delayed recovery of memory B cells with an abnormal cell marker expression
      and function demonstrates that naive B cells may fail to differentiate into
      plasma cells, resulting in hypogammaglobulinaemia after autologous SCT and
      rituximab therapy.

PMID- 17456058
TI  - Graft-versus-leukaemia effect after non-myeloablative haematopoietic
      transplantation can overcome the unfavourable expression of ZAP-70 in refractory
      chronic lymphocytic leukaemia.
AB  - ZAP-70 (zeta-chain-associated protein 70 kDa) expression is associated with poor
      prognosis in patients with chronic lymphocytic leukaemia (CLL). This study
      evaluated the efficacy of non-myeloablative allogeneic stem cell transplantation
      in patients with advanced CLL and assessed the impact of ZAP-70 expression on the
      outcome. Thirty-nine sequential patients were included. All had previously been
      treated with fludarabine. All patients received a preparative regimen of
      fludarabine (30 mg/m(2)/d for 3 d), intravenous cyclophosphamide (750 mg/m(2)/d
      for 3 d), and high-dose rituximab. Immunohistochemical techniques on marrow
      biopsy samples were used to determine that ZAP-70 was expressed in 25 patients,
      whereas 13 other patients were ZAP-70 negative, and one was of indeterminate
      status. With a median follow-up time of 27 months, the estimated overall survival
      and current progression-free survival (CPFS) rates at 4 years were 48% and 44%
      respectively. Patients who were ZAP-70 positive had 56% survival, and their CPFS
      rate increased from 30% to 53% after a donor lymphocyte infusion. Multivariate
      analysis indicated that chemorefractory disease and mixed T cell chimerism at day
      90, but not ZAP-70 positivity, were associated with the risk of disease
      progression after transplantation. These results demonstrate a potent graft
      versus-leukaemia effect that can overcome the adverse prognostic effect of ZAP-70
      expression.

PMID- 17456059
TI  - The number of tumour-infiltrating TIA-1+ cytotoxic T cells but not FOXP3+
      regulatory T cells predicts outcome in diffuse large B-cell lymphoma.
AB  - The prognostic significance of tumour-infiltrating lymphocytes (TILs) in patients
      with diffuse large B-cell lymphoma (DLBCL) remains controversial. Furthermore,
      the possible impact of regulatory T cells (T(regs)) on survival in DLBCL is still
      unknown. We performed a retrospective study on the immunohistochemical expression
      of cytotoxic cells and T(regs), and their correlation with survival in 195 DLBCL
      patients. Patients with a small number of cytotoxic T-cell intracytoplasmic
      antigen-1 (TIA-1)+ T cells (< or =260 cells/mm(2) tumour area; n = 52) had
      significantly better outcome than patients with a large number (>260 cells/mm(2);
      n = 143); progression-free survival (PFS) at 5 years was 67% vs. 50% (P = 0.03)
      and overall survival (OS) was 73% vs. 57% (P = 0.03). In multivariate analysis,
      the low TIA-1+ group still had a better PFS (relative risk 0.75, 95% confidence
      interval 0.31-0.99; P = 0.05). The number of forkhead box protein 3 (FOXP3)+
      T(regs) had no influence on PFS (P = 0.89) or OS (P = 0.75). These results
      suggest that immunohistochemical analysis of cytotoxic T cells at time of
      diagnosis could provide additional prognostic information. The lack of
      correlation between the number of FOXP3+ cells and survival could possibly
      indicate that tumour-infiltrating T(regs) are of less clinical importance in
      DLBCL. However, these findings need to be explored in functional studies.

PMID- 17456060
TI  - Hybrid eosinophilic-basophilic acute myeloid leukaemia diagnosed by electron
      microscopy.

PMID- 17456061
TI  - The prevalence of valvular abnormalities in patients who were referred for
      echocardiographic examination with a primary diagnosis of "heart murmur".
AB  - INTRODUCTION: The prevalence of valvular abnormality and innocent murmur in
      patients who are referred for echocardiographic evaluation with the diagnosis of
      "murmur" is not known. The goal of this study was to evaluate the prevalence of
      valvular abnormalities in such patients. METHODS: We retrospectively reviewed the
      echocardiograms that were referred with the primary ordering diagnosis of
      "murmur," for the presence of valvular abnormalities. For comparison, we used
      other documented primary reasons for echocardiographic referral, such as chest
      pain, shortness of breath, etc. RESULTS: In this cohort, 7,684 echocardiogram
      reports documented primary diagnostic reasons for echocardiographic referral. A
      total of 3,460 echocardiogram reports (45%) were coded "murmur" as the primary
      reason for the study referral. There was a higher prevalence of female patient
      referrals for heart murmur evaluation (61.8% vs. 38.2%). Although, patients with
      murmur had a higher prevalence of valvular abnormalities, compared to other
      reasons for echocardiographic examination, the prevalence of valvular abnormality
      was less than 50% (48.6% vs. 35.5%) in both groups. Despite the higher number of
      female patients referred with the diagnosis of murmur, the percentage of abnormal
      valves was lower in women (45.6% vs. 53.4% in men). CONCLUSION: The prevalence of
      valvular abnormalities in patients who were referred with the diagnosis of murmur
      for echocardiographic examination was less than 50%, with a lesser degree found
      in women. Routine utilization of echocardiography for evaluation of all murmurs
      may be unwarranted.

PMID- 17456062
TI  - Two-dimensional assessment of right ventricular function: an echocardiographic
      MRI correlative study.
AB  - BACKGROUND: While echocardiography is used most frequently to assess right
      ventricular (RV) function in clinical practice, echocardiography is limited in
      its ability to provide an accurate measure of RV ejection fraction (RVEF). Hence,
      quantitative estimation of RV function has proven difficult in clinical practice.
      OBJECTIVE: We sought to determine which commonly used echocardiographic measures
      of RV function were most accurate in comparison with an MRI-derived estimate of
      RVEF. METHODS: We analyzed RV function in 36 patients who had cardiac MRI studies
      and echocardiograms within a 24 hour period. 2D parameters of RV function-right
      ventricular fractional area change (RVFAC), tricuspid annular motion (TAM), and
      transverse fractional shortening (TFS) were obtained from the four-chamber view.
      RV volumes and EFs were derived from volumetric reconstruction based on
      endocardial tracing of the RV chamber from the short axis images.
      Echocardiographic assessment of RV function was correlated with MRI findings.
      RESULTS: RVFAC measured by echocardiography correlated best with MRI-derived RVEF
      (r = 0.80, P < 0.001). Neither TAM (r = 0.17; P = 0.30) nor TFC (r = 0.12; p<
      0.38) were significantly correlated with RVEF. CONCLUSIONS: RVFAC is the best of
      commonly utilized echocardiographic 2D measure of RV function and correlated best
      with MRI-derived RV ejection fraction. CONDENSED ABSTRACT: While echocardiography
      is used most frequently to assess RV function in clinical practice,
      echocardiography is limited in its ability to provide an accurate measure of RV
      ejection fraction (RVEF). Using cardiac MRI, RV fractional area change (RVFAC),
      determined either by MRI or echocardiography, was found to correlate best with
      MRI-derived RVEF.

PMID- 17456063
TI  - Preserved Windkessel function in patients following reduction aortoplasty of the
      ascending aorta.
AB  - OBJECTIVE: Reduction ascending aortoplasty (RAA) is a controversial procedure.
      Agreement has not yet been made regarding the indication for surgery and surgical
      technique. The goal of this study was to examine the long-term outcome of RAA
      without external support, and to compare the accuracy of transthoracic
      echocardiographic with computed tomographic (CT) measurements. Of particular
      interest was whether the important elastic properties of the aorta, the
      Windkessel function, is preserved following reduction aortoplasty of the
      ascending aorta without external wrapping. METHODS: Ninety-eight patients with
      dilation of the ascending aorta underwent reduction aortoplasty with concomitant
      cardiac procedures. Fifty-four patients were available for follow-up. Measurement
      of the ascending aortic diameter was performed prior to and directly following
      surgery, and 37 months postoperatively (range: 10-96 months). Both
      echocardiography and CT imaging were performed. The elastic properties of the
      ascending aorta were determined by measuring the distension of the ascending
      aorta during diastole and systole by means of transthoracic echocardiography.
      Fifteen patients with graft replacement of the ascending aorta were examined, and
      the control group contained 11 healthy volunteers. RESULTS: The diameter of the
      ascending aorta was significantly reduced in all patients who had undergone RAA.
      The change in diameter between diastole and systole was 3 mm in patients with
      reduction aortoplasty. Patients with graft replacement had a change of only 0.07
      cm. There was no relevant increase (2 mm) in diameter at follow-up.
      Echocardiographic and CT measurements of the aortic diameter did not differ.
      CONCLUSIONS: RAA without external wrapping shows good long-term results in
      patients with a dilated ascending aorta who underwent concomitant cardiac
      procedures. Echocardiography is very accurate in measuring the ascending aortic
      diameter, which makes it a cost-effective diagnostic tool. Moreover, ascending
      aortoplasty without external wrapping preserves the important elastic properties,
      namely the Windkessel function. Follow-up of the cardiac function and aortic
      diameter can be performed easily and precisely in the outpatient setting.

PMID- 17456064
TI  - Assessment of mitral inflow during standardized Valsalva maneuver in
      stratification of diastolic function.
AB  - BACKGROUND: We assessed the changes of mitral inflow during Valsalva maneuver
      (VM) in patients with different stages of left ventricular dysfunction and
      evaluated their value for the differentiation between normal and pseudonormal
      filling pattern. METHODS: A total of 190 patients (120 with coronary artery
      disease, and 70 healthy subjects) were examined by transthoracic
      echocardiography. Mitral E/A ratio, early wave deceleration time (Edt), and
      pulmonary vein flow (especially atrial reversal parameters (Ar)), were used for
      the initial stratification to normal, delayed relaxation, pseudonormal, and
      restrictive profiles. Changes of mitral inflow during VM were compared between 54
      normal (N) and 15 pseudonormal (PN). RESULTS: During VM, a similar decrease in
      early wave peak velocity (-30 +/- 18 vs -35 +/- 17 cm/sec), peak velocity of
      atrial wave (-6 +/- 16 vs -8 +/- 17 cm/sec), and E/A ratio (-0.4 +/- 0.4 vs -0.4
      +/- 0.4) was observed in both groups. Only two filling variables, related to
      atrial phase of inflow, changed in the opposite direction. In normal pattern, the
      duration and velocity-time integral of atrial wave diminished during VM as
      opposed to pseudonormal subjects (DeltaAt -7 +/- 39 vs 20 +/- 44 msec; P < 0.05
      and DeltaA vti -0.7+/-1.8 vs 0.4+/-2 cm; P < 0.05). Increase in peak atrial
      velocity and marked decrease in E/A ratio during VM were specific for the
      restrictive group. CONCLUSIONS: Changes of mitral inflow during VM have a
      moderate diagnostic value for the differentiation of normal and pseudonormal
      pattern. Increased duration of atrial phase but not increase in atrial velocity
      allowed the diagnosis of pseudonormalization.

PMID- 17456065
TI  - Reversal E/A value at end-inspiration might be more sensitive and accurate for
      diagnosing abnormal left ventricular diastolic function.
AB  - BACKGROUND: It is well known that left ventricular (LV) filling decreases on
      inspiration and increases on expiration; however, respiratory effects on
      diastolic function have not been fully investigated. AIM: This study attempted to
      provide further information on the precise diagnosis of LV diastolic dysfunction
      when taking respiration into account. METHODS: Fifty-one patients with systemic
      hypertension and impaired LV diastolic function and 33 normal subjects were
      recruited. Respiratory transmitral Doppler flow parameters and the early-to-late
      diastolic tissue velocity ratio of the mitral annulus (e/a ratio) of the septal
      wall were recorded. The validity of the reversal ratio of early-to-late peak flow
      velocity (E/A ratio) on inspiration and on expiration for diagnosis of diastolic
      dysfunction was compared. RESULTS: The E velocity was much higher and its
      deceleration time was much shorter on expiration compared to that on inspiration,
      while the A velocity demonstrated no regular respiratory variations both in
      normal subjects and patients. Ten of the patients displayed a phenomenon
      characterized with an E/A ratio < 1 on inspiration and > 1 on expiration, eight
      of whom revealed abnormal LV filling by Tissue Doppler imaging. CONCLUSION:
      Respiratory effects on transmitral Doppler flow parameters raise the necessity of
      adjustment of the existing standard for precise diagnosis of diastolic
      dysfunction, while the characteristic phenomenon reported here indicates that
      reversal E/A value on end-inspiration is a more sensitive and accurate indicator
      of abnormal LV diastolic function.

PMID- 17456066
TI  - Role of tissue Doppler and color M-mode imaging for evaluation of diastolic
      function in ambulatory patients with LV systolic dysfunction.
AB  - INTRODUCTION: Tissue Doppler imaging (TDI) and color M-mode (CMM) indices provide
      assessment of left ventricular (LV) relaxation when combined with pulse-wave
      Doppler (PWD)-derived transmitral inflow, allows for estimation of LV filling
      pressures. However, use of these indices in patients with LV systolic dysfunction
      (LVSD) has not been well characterized. METHODS AND RESULTS: The study included
      115 patients (age 58 +/- 11 years, 67% male) with LVSD (LV ejection fraction
      [LVEF] < 55%). Patients were grouped according to the diastolic LV filling
      pressure assessed by E/Em(septal) ratio as follows: 1) Normal (NFP), E/Em(septal)
      < 8; 2) Intermediate (IFP), E/Em(septal): 8-15; and 3) High (HFP), E/Em(septal)
      >15. Age-, gender-, and LVEF-adjusted analyses were performed. LV volumes and
      LVEF were significantly different between the groups (P < 0.01). PWD-derived E
      wave velocity showed a significant stepwise increase across the three groups and
      the Em(septal) velocity demonstrated a stepwise decrease (P < 0.01 for both). CMM
      derived diastolic intra-ventricular pressure gradient (IVPG) was significantly
      lower in the HFP compared to the other 2 groups (P < 0.01 for both); Vp was
      increased in the HFP compared to the other 2 groups (P < 0.01 for both), and Vp
      exhibited a U-shape relationship to LVEF. CONCLUSION: In patients with LVSD,
      abnormal LV relaxation is uniformly observed regardless of LV filling pressure.
      PWD-derived E-wave velocity and the TDI-derived Em velocity are important
      measurements to identify elevated LV filling pressures. CMM-derived Vp and IVPG
      were of limited incremental value for the evaluation of diastolic function in
      patients with LVSD.

PMID- 17456067
TI  - Tissue Doppler imaging in the evaluation of the left and right ventricular
      diastolic functions in rheumatoid arthritis.
AB  - OBJECTIVE: Previous studies have reported that cardiovascular involvement in
      rheumatoid arthritis (RA) occurs frequently. Although ventricular functions of RA
      have been investigated through the standard Doppler in RA, they have yet to be
      investigated thoroughly by means of the relatively new and advantageous tissue
      Doppler imaging (TDI). The present study aims to investigate left and right
      ventricular functions in RA patients by means of TDI and standard Doppler
      echocardiography. METHODS: A total of 60 patients with longstanding RA and 40
      control subjects were included in the study and their left and right ventricular
      functions were assessed by standard pulsed-wave Doppler echocardiography, the
      color M-mode flow propagation velocity, and TDI. The left ventricular TDI was
      achieved at four different sites (lateral, septal, anterior, and inferior walls),
      while the right ventricular TDI was achieved through the tricuspid lateral
      annulus. RESULTS: When compared with controls, the RA group showed that basal
      clinic and echocardiographic parameters, early (E) and late (A) diastolic
      velocities of atrioventricular valves, E/A ratio, and pulmonary venous Doppler
      parameters of these two groups were similar. It was determined that left and
      right ventricular E-wave deceleration times and isovolumic relaxation times of
      the RA patients were determined to have increased in comparison with those of the
      subjects in the healthy Control Group (P < 0.05). RA patients had significantly
      lower color M-mode flow propagation velocity (P < 0.05). While S' peak and E'
      peak, two of the left and right ventricular TDI parameters, were similar in both
      groups, A' peak, E'/A', and E/E' parameters in RA showed statistically
      significant differences in RA patients. CONCLUSION: A comparison between age and
      sex of RA patients and healthy individuals revealed that left and right
      ventricular TDI parameters of RA patients were impaired, which led us to conclude
      that both of the ventricles could have been involved.

PMID- 17456068
TI  - Longitudinal diastolic myocardial functions are affected by chronic smoking in
      young healthy people: a study of color tissue Doppler imaging.
AB  - AIMS: Many cardiac and hemodynamic alterations occur after acute consumption of
      cigarettes. The aim of this study is to evaluate the effect of chronic smoking on
      longitudinal myocardial functions of left ventricle in young, healthy people by
      using color tissue Doppler imaging modalities. METHODS AND RESULTS: Ninety-nine
      healthy participants were studied. There were 65 smokers and 34 nonsmokers. All
      subjects were between 20 and 35 years old. Sample volumes were placed on the mid
      left ventricle in the inner half of the myocardium at the septum, lateral,
      inferior, and anterior walls. The peak systolic strain (S-S), peak systolic
      strain rate (S-SR), peak early diastolic SR (E-SR), peak late diastolic SR (A
      SR), peak systolic tissue velocity (S-TV), peak early diastolic TV (E-TV), and
      peak late diastolic TV (A-TV) values were measured. For the systolic parameters S
      S, S-SR, and S-TV values were not different between the groups. For the diastolic
      parameters smokers had lower E-SR and E-TV values than nonsmokers (P = 0.03 for
      both). Although there was a trend toward higher A-SR and A-TV values in the
      smokers, they were not reaching the statistical significance. CONCLUSION: Chronic
      smoking in young, healthy people causes significant alterations in the
      longitudinal diastolic myocardial function parameters as assessed by color tissue
      Doppler imaging.

PMID- 17456069
TI  - Usefulness of bedside tissue Doppler echocardiography and B-type natriuretic
      peptide (BNP) in differentiating congestive heart failure from noncardiac cause
      of acute dyspnea in elderly patients with a normal left ventricular ejection
      fraction and permanent, nonvalvular atrial fibrillation: insights from a
      prospective, monocenter study.
AB  - BACKGROUND: The incremental role of bedside tissue Doppler echocardiography and B
      type natriuretic peptide (BNP) over the clinical judgment has been recently
      reported in the emergency diagnosis of congestive heart failure with a normal
      left ventricular ejection fraction (HFNEF). However, how well does this
      diagnostic strategy be applicable in the setting of atrial fibrillation is
      unknown. OBJECTIVE: To investigate the usefulness of bedside tissue Doppler
      echocardiography and BNP in the emergency diagnosis of HFNEF in elderly patients
      with permanent, nonvalvular atrial fibrillation. METHODS: Forty-one consecutive
      elderly patients with an ejection fraction > or =50% (mean age 84 years; 22 with
      HFNEF and 19 with noncardiac cause), hospitalized for acute dyspnea at rest, were
      prospectively enrolled; bedside septal E/Ea and BNP were obtained at admission.
      RESULTS: By multivariable logistic regression analysis including the clinical
      judgment of heart failure, E/Ea and BNP, E/Ea (P = 0.014) and BNP (P = 0.018)
      provided independent diagnostic information. Optimal cutoffs were 13 for E/Ea
      (area under the ROC curve of 0.846, P < 0.0001; sensitivity 81.8%, specificity
      89.5%) and 253 pg/ml for BNP (area under the ROC curve of 0.928, P < 0.0001;
      sensitivity 86.4%, specificity 89.5%). The concordance between the clinical
      judgment and BNP concentration at the cutoff of 253 pg/ml correctly classified 24
      of 25 patients; E/Ea at the cutoff of 13 correctly classified 14 of the 16
      patients with discrepancy. CONCLUSION: Bedside tissue Doppler echocardiography
      and BNP provide useful additional diagnostic information over the clinical
      judgment for the emergency diagnosis of HFNEF in elderly patients with permanent,
      nonvalvular atrial fibrillation.

PMID- 17456070
TI  - Correlation between Doppler derived dP/dt and left ventricular asynchrony in
      patients with dilated cardiomyopathy: A combined study using strain rate imaging
      and conventional Doppler echocardiography.
AB  - AIM: To evaluate the relationship between Doppler-derived left ventricular (LV)
      dP/dt and the degree of LV mechanical asynchrony measured by strain rate imaging.
      METHODS AND RESULTS: The study group consisted of 69 patients with variable
      degree of LV dysfunction and mitral regurgitation (MR). Conventional echo
      variables and LV dP/dt were calculated from the MR Doppler spectrum by rate
      pressure-rise method. Strain rate traces were obtained by 12-segment model and LV
      long axis images were analyzed off-line. The longest time intervals between the
      peak negative strain rate waves at isovolumic contraction period and peak systole
      from reciprocal segments were defined as asynchrony index AIc or AIs,
      respectively. The maximum differences in time-to-peak systolic velocities between
      opposing walls were also measured as asynchrony index by tissue Doppler (AItd).
      The dP/dt, mean QRS duration, AIc, AIs, and AItd were 836 +/- 266 mmHg/sec, 125
      +/- 31, 38 +/- 28, 64 +/- 44, and 52 +/- 32 m, respectively. No significant
      correlation between the dP/dt and the LV dimension, ejection fraction or QRS
      duration was observed. However, dP/dt correlated negatively with AIc, or AIs (r:
      0.78, -0.72, P < or = 0.0001) and AItd (r:-0.65, P < or = 0.001). A cutoff dP/dt
      value of under 700 mmHg/sec can discriminate patients over median AIs (55 ms) or
      patients with AIc over 30 ms with high sensitivity and specificity. CONCLUSIONS:
      Doppler-derived LV dP/dt is related to the degree of LV dyssynchrony rather than
      the conventional systolic function indices such as EF% in patients with severe
      heart failure. Noninvasive dP/dt assessment in addition to advanced imaging
      techniques can be used to define patients for cardiac resynchronization therapy
      (CRT).

PMID- 17456071
TI  - Clinical and echocardiographic risk factors for embolization in the presence of
      left atrial thrombus.
AB  - AIMS: The aim of our study was to evaluate the factors leading to embolization in
      patients with left atrial thrombi (LAT). With this purpose, we retrospectively
      analyzed clinical, transthoracic, transesophageal echocardiographic data of
      patients with LAT in the transesophageal echocardiographic evaluation. METHODS
      AND RESULTS: One hundred ninety-two patients with LAT not on anticoagulant
      therapy were divided into two groups according to the presence of prior ischemic
      stroke. The group with ischemic stroke included more patients with sinus rhythm
      and less patients with mitral stenosis. They had smaller left atrial diameter,
      more left atrial appendage spontaneous echo-contrast, higher appendage ejection
      fraction, and emptying velocity. CONCLUSION: Once the thrombus has been formed,
      cerebral embolization seems to be higher in patients with relatively preserved
      appendage ejection fraction and emptying velocity. Presence of atrial appendage
      spontaneous echo-contrast also favor embolization. Factors leading to
      embolization seem to differ in some respects from the causes of thrombus
      formation.

PMID- 17456072
TI  - Right ventricular tissue Doppler and strain imaging: ready for clinical use?
AB  - Although tissue Doppler (TD) imaging of the left ventricle is now commonly used
      in clinical settings, TD imaging of the right ventricle (RV) is not routinely
      practiced. Yet, there are significant data on clinical uses of RV TD imaging,
      including established normal values using both color and spectral TD. In acute
      left ventricular (LV) inferior wall myocardial infarction, depressed RV TD
      velocities have been shown to correlate with the presence of RV impairment, and
      with patient outcome. In patients with LV heart failure, TD imaging has been
      correlated to RV ejection fraction by radionuclide angiography, and is an
      independent predictor of outcome. In patients with congenital heart disease, RV
      TD has been especially valuable for assessing RV function, and has been
      correlated to invasive hemodynamic indices, and RV ejection fraction by magnetic
      resonance imaging. The RV performance (Tei) index has been calculated and
      validated using TD-derived, rather than conventional pulsed Doppler time
      intervals. RV TD indices have been shown to be useful in the detection of
      subclinical and clinical disease in morbid obesity, chronic pulmonary, and
      systemic disease. TD-derived RV strain imaging can detect segmental myocardial
      dysfunction, overcoming limitations to conventional TD imaging resulting from
      tethering. For both TD velocity and strain imaging, however, appreciation of the
      limitations of these techniques is necessary for their appropriate use. Given its
      rapid acquisition times, reproducibility, and ease of addition to standard
      transthoracic echocardiographic protocols, RV TD and strain imaging are important
      additional modalities in the comprehensive echo-Doppler assessment of RV
      function.

PMID- 17456073
TI  - Utility of intracardiac echocardiography in left heart ablation for
      tachyarrhythmias.
AB  - Catheter-based radiofrequency ablation in the left heart can provide effective
      therapy for tachyarrhythmias. The recent development of the real time
      intracardiac echocardiography (ICE) with 2D and Doppler color flow imaging can
      facilitate left heart ablation procedures. This report reviews the use of ICE
      during radiofrequency catheter ablation procedures for atrial fibrillation (AF)
      and ventricular tachycardia and is based on our own experience in 955 patients.
      ICE has a critical role for guiding transseptal catheterization, assisting
      placement of mapping/ablation catheters and monitoring lesion morphologic
      changes, especially in the pulmonary vein ostia, Marshall ligament region,
      thickened interatrial septum, left atrial posterior wall contiguous to esophagus,
      aortic valve cusps, and the epicardial regions. One of the more powerful
      utilities of ICE lies in its ability to identify and potentially reduce
      procedural complications including damage to intracardiac structures, residual
      atrial septal defect, left atrial thrombus formation, pulmonary vein stenosis,
      esophageal injury, myocardial air-embolization and pericardial effusion during
      left heart ablation.

PMID- 17456074
TI  - Live/real time three-dimensional transthoracic echocardiographic assessment of
      tricuspid valve pathology: incremental value over the two-dimensional technique.
AB  - Twenty-nine patients with different tricuspid valve (TV) pathologies were studied
      by both two-dimensional transthoracic (2DTTE) and live/real time three
      dimensional transthoracic echocardiography (3DTTE). A major contribution of 3DTTE
      over 2DTTE was the en face visualization of all three leaflets of the TV in all
      patients. This allowed accurate assessment of TV orifice area in patients with TV
      stenosis and carcinoid disease. Loss of TV leaflet tissue, defects in TV leaflets
      and size of TV systolic non-coaptation could also be delineated and resulted in
      identifying the mechanism of tricuspid regurgitation (TR) in patients with
      Ebstein's anomaly and rheumatic heart disease. Prolapse of TV leaflets could also
      be well visualized and enabled us to develop a schema for systematic assessment
      of individual segment prolapse which could help in surgical planning. The exact
      sites of chordae rupture in patients with flail TV as well as right ventricular
      papillary muscle rupture could be well seen by 3DTTE. 3DTTE also permitted
      sectioning of various TV masses for more specific diagnosis of their nature. In
      addition, color Doppler 3DTTE provided an estimate of quantitative evaluation of
      TR severity, since the exact shape and size of the vena contracta could be
      accurately assessed. In conclusion, our preliminary experience with 3DTTE has
      demonstrated substantial incremental value over 2DTTE in the assessment of
      various TV pathologies.

PMID- 17456075
TI  - Diagnostic value of dobutamine stress echocardiography in patients with normal
      wall motion at rest.

PMID- 17456076
TI  - Tiger stripes.

PMID- 17456077
TI  - Percentage of body recovered and its effect on identification rates and cause and
      manner of death determination.
AB  - Anthropologists frequently encounter cases in which only partial human remains
      are recovered. This study reports how the percentage of the body recovered
      affects identification (ID) rates and cause and manner of death determination. A
      total of 773 cases involving anthropology consults were drawn from the New Mexico
      medical examiner's office (1974-2006). Results indicate a significant correlation
      between body percent recovered and ID rates, which ranged from 89% for complete
      bodies to 56% when less than half the body was present. Similar patterns were
      evident in cause/manner determination, which were the highest (83% and 79%,
      respectively) in complete bodies but declined to 40% when less than half the body
      was found. The absence of a skull also negatively impacted ID and ruling rates.
      Findings are compared with general autopsy ID rates (94-96%) and cause/manner
      determination rates (96-99%) as well as prior published rates for individual
      casework and mass death events.

PMID- 17456078
TI  - An anthropological analysis of gunshot wounds to the chest.
AB  - This analysis of gunshot trauma to the bony thorax examines 87 handgun and rifle
      wounds from documented cases in an effort to corroborate an earlier report and to
      provide the forensic community with additional literature in this area.
      Specifically, this study tests whether the trauma signatures associated with
      gunshot wounds in the bony thorax are useful in determining the direction of
      fire. Because the ribs occupy a significant portion of the bony thorax, they are
      struck more frequently than other bones and, consequently, they are the focus of
      this report. This study confirmed that bullets can leave distinctive markers on
      ribs that indicate the direction of fire, including depressed fractures, bone
      fragments displaced in the direction of the bullet's path, and beveling. Although
      forensic anthropologists can determine the direction that a bullet was traveling
      when it struck a given rib, they cannot give a definitive statement about the
      number or sequence of gunshots without supporting soft tissue evidence.

PMID- 17456079
TI  - Stature estimation of 3-10-year-old children from long bone lengths.
AB  - Estimation of stature in adult forensic cases with available long bones of the
      limbs is routine, but such estimation is less common in subadult cases. Long
      bones from subadult cases are often used to estimate age, but in some instances
      stature may be helpful or even critical for identification. Few published
      regression equations exist for consultation in such cases. Data from the
      longitudinal growth study conducted by the Child Research Council in Denver in
      the mid-1900s are utilized to produce dual-sex and single-sex regression
      equations for the six long bones of the limbs (humerus, radius, ulna, femur,
      tibia, and fibula) and for the combined femur+tibia length. All measurements are
      from radiographs and are of diaphyseal length. Examples show that similar results
      can be obtained using a two-step process of "ballpark" estimation from published
      tables of the Denver data, but these new regressions allow a one-step standard
      error estimate for the means. Regressions are further compared with those
      previously published by Finnish researchers, which are generally broadly
      comparable. More routine stature estimation in subadult cases is encouraged both
      as an aid to possible identification and as a test of the available regression
      equations.

PMID- 17456080
TI  - Prediction of stature based on radiographic measurements of cadaver long bones: a
      study of the Croatian population.
AB  - We tested a new approach to the stature prediction that could be used in the
      identification process of human skeletal remains of unknown identity. The stature
      of 19 female and 21 male adult cadavers was measured within 24 h after death and
      considered to be equal to the living stature. The antero-posterior radiographs of
      all limbs were taken, and the maximum length of the six long bones was measured
      from radiographs. There was a significant difference in the stature and maximum
      length of long bones between female and male cadavers (p<0.001 for all). The
      correlation between the stature and long bone length was the best for the humerus
      in females (r=0.792) and the tibia in males (r=0.891). Regression equations
      specific to the Croatian population were computed separately for each long bone
      in males and females and proven to be reliable in predicting the living stature
      of the individual.

PMID- 17456081
TI  - Evaluation of Purkait's triangle method for determining sexual dimorphism.
AB  - The identification of sex from the skeleton is an important demographic
      assessment in medicolegal investigations. Rama Purkait developed a method for
      estimating sex using measurements from a triangle defined by three points on the
      proximal end of the femur using skeletal material from Bhopal, India. This method
      was tested with measurements on 200 Indo-European and African American adult
      femora from the Terry collection using discriminant function analysis to
      determine if Purkait's method was valuable for determining sex in Americans. A
      side-by-side analysis was conducted of Purkait's "triangle method" and the
      maximum diameter of the femoral head to determine their relative value in
      assessing sexual dimorphism. In the study sample a single variable from Purkait's
      method provided 85.5% prediction accuracy, similar to 87% for the head diameter.
      Combining threshold values for a single variable from Purkait's method and the
      femoral head diameter raised the predictability to greater than 90% for both
      sexes.

PMID- 17456083
TI  - Mitochondrial DNA analysis of the domestic dog: control region variation within
      and among breeds.
AB  - The mitochondrial DNA (mtDNA) control regions of 125 domestic dogs (Canis
      familiaris) encompassing 43 breeds, as well as one coyote and two wolves were
      sequenced and subsequently examined for sequence variation in an effort to
      construct a reference dog mtDNA data set for forensic analysis. Forty informative
      variable sites were identified that described 45 haplotypes, 29 of which were
      observed only once. Substantial variation was found both within and among breeds
      in the mtDNA derived from tissue, indicating that analysis of the mtDNA derived
      from dog hairs could be a valuable, discriminating piece of evidence in forensic
      investigations. The dog data set single nucleotide polymorphisms (SNPs) ranged
      from having one to six changes on a phylogenetic tree. On average, there were 1.9
      character changes for each variable position on the tree. The most variable sites
      (with four or more changes each, listed from the most changes to the fewest)
      observed were 15,639 (L=6), 16,672 (L=5), 15,955 (L=4), 15,627 (L=3), 16,431
      (L=3), and 16,439 (L=3). These sites were consistent with other reports on
      variable positions in the dog mtDNA genome. A total of 26 SNPs were chosen to
      best identify all major clusters in the domestic dog data set. The descriptive
      analyses revealed that this data set is similar to other published canine data
      sets and further demonstrates that this domestic dog data set is a useful
      resource for forensic applications. This reference data set has been compiled and
      validated against the published dog genetic literature with an aim to aid
      forensic investigations that seek to incorporate mtDNA sequences and SNPs from
      trace evidence such as dog hair.

PMID- 17456082
TI  - Forensic mitochondrial DNA analysis of 116 casework skeletal samples.
AB  - Between February 1999 and May 2005, 116 DNA extractions were completed on
      skeletal remains from routine casework. Overall, at least a partial mitochondrial
      DNA (mtDNA) profile was obtained on 83.6% of samples. Skeletal remains fell into
      two general categories: (1) samples for body identifications submitted by law
      enforcement and (2) samples submitted to answer historical or family identity
      questions. Body identification cases were more likely to yield full mtDNA
      profiles, whereas historical cases were more likely to result in partial
      profiles. Overall, the ability to obtain a full or partial profile primarily
      reflects the difference in the average age and condition of the samples in these
      two categories and thus, difference in the quantity and quality of the DNA.
      Cremated remains were uniformly unsuccessful, whereas infant/fetal remains were
      uniformly successful. Heteroplasmy in skeletal remains was observed at a rate
      similar to that in hair ( approximately 10%). For body identification cases,
      skeletal remains had the same mtDNA profile as the accompanying reference sample
      in 50% of cases.

PMID- 17456084
TI  - Apparent effects of glyphosate on alkaloid production in coca plants grown in
      Colombia.
AB  - During the routine analysis of coca leaf material from South America, alkaloids
      in Erythroxylum coca var. ipadu (ECVI) leaf samples from fields suspected of
      being treated with glyphosate were compared with those from non-treated E. coca
      var. ipadu and Erythroxylum novogranatense var. novogranatense (ENVN) plants.
      Cocaine levels in leaf tissue from non-treated ECVI and ENVN were 0.53+/-0.08%
      and 0.64+/-0.08% (w/w), respectively, whereas leaves from treated plants were
      nearly devoid of cocaine. Further analysis demonstrated the presence of several
      previously undescribed N-nortropane alkaloids, several of which were tentatively
      identified. The results suggest that applications of glyphosate to coca plants
      can have dramatic effects on the quantity and quality of alkaloids produced by
      surviving or subsequent leaves. The analytical data presented will be of value to
      forensic chemists who encounter illicit cocaine preparations containing alkaloids
      produced from coca plants treated with glyphosate.

PMID- 17456085
TI  - Performance testing of commercial containers for collection and storage of fire
      debris evidence.
AB  - Fire debris evidence may contain ignitable liquid residues valuable in the
      investigation of a potential arson scene. The ability to obtain evidence
      containers that are contaminant-free and vapor-tight is essential to the analysis
      and storage of fire debris evidence. Commercial containers such as metal "paint"
      cans, glass mason jars, and polymer bags are often employed as fire debris
      evidence containers. The purpose of this research was to determine which of these
      three types of containers provided the most vapor-tight seal for the prevention
      of ignitable liquid vapor loss and to assess the potential for cross
      contamination. Leak rates for each type of container were measured under
      controlled conditions. Simple mixtures of hydrocarbons were utilized in these
      experiments. Leak rates were determined based on the amounts of hydrocarbon
      recovered from activated charcoal located outside the test container and within a
      secondary container. Quantitation of the hydrocarbons recovered from activated
      charcoal was calculated using external standard calibration curves following
      analysis by gas chromatography-mass spectrometry. The results demonstrated that
      glass jars had the fastest leak rate followed by metal paint cans and properly
      heat-sealed polymer bags with the slowest leak rate. Each container exhibited a
      different leak mechanism, which resulted in an observable effect on the
      composition of hydrocarbons lost from the container. Hydrocarbon transfer from
      one container to another is also demonstrated. This study presents results that
      reveal the most vapor-tight container to be a properly heat-sealed copolymer bag.

PMID- 17456086
TI  - Defending the scientific foundations of the firearms and tool mark identification
      discipline: responding to recent challenges.
AB  - Recent challenges have brought the discipline of firearms and tool mark
      identification to the forefront in recent court cases. This article reviews those
      challenges and offers substantial support for the scientific foundations of the
      firearms and tool mark identification discipline. A careful review of the
      available literature has revealed that firearms and tool mark identification is
      rooted in firm scientific foundations, critically studied according to the
      precepts of the scientific method culminating in the Association of Firearms and
      Toolmark Examiners' Theory of Identification. Firearms and tool mark
      identification has been validated in a manner appropriate for evidence of the
      kind to be expected in firearms and tool mark examinations. Proficiency tests and
      error rates have been studied and can provide consumers of the disciple with a
      useful guide as to the frequency with which misidentifications are reported in
      the community using appropriate methodologies and controls. As a result, the
      primary issues in recent challenges do not invalidate the firearms and tool mark
      discipline as a science nor should it detract it from its admissibility in a
      court of law.

PMID- 17456087
TI  - Identification of organic pigments in automotive coatings using laser desorption
      mass spectrometry.
AB  - When one looks at an automotive coating, one sees color due to pigments. Modern
      organic pigments, with high molar absorptivities, may be only minor components of
      the mixture. Laser desorption mass spectrometry (LDMS) has been shown to be a
      useful tool for the analysis of colorants such as pen ink dyes. Here, LDMS is
      used to determine its utility for the identification of pigments, in simple media
      and in more complex paints. Small paint chips can be introduced into the LDMS
      instrument, and when an ultraviolet laser is focused on a portion of a chip, ions
      representative of the pigment(s) are selectively formed. Some pigments such as
      quinacridones and copper phthalocyanine are very stable and are desorbed and
      ionized intact. In contrast, benzimidazolones, which contain some single-skeletal
      bonds, form fragment ions. This method proves to be sensitive and convenient, as
      no sample preparation is required. The presence of inorganic pigments in addition
      to modern organic pigments can be determined, and pigments can be directly
      identified in actual automotive paint chip samples.

PMID- 17456088
TI  - Effect of electron beam irradiation on forensic evidence. 2. Analysis of writing
      inks on porous surfaces.
AB  - The effect of electron beam irradiation on a series of different writing inks is
      described. As the anthrax-tainted letters were discovered in October 2001, the
      U.S. government began to experiment with the use of the electron beam irradiation
      process for destroying such biological agents. Plans initially considered a large
      scale countrywide use of this technology. However, over time the scope of this
      plan as well as the radiation dosage were reduced, especially when some adverse
      consequences to mailed items subjected to this process were observed. Little data
      existed at the time to characterize what level of damage might be expected to
      occur with common items sent through the mail. This was especially important to
      museums and other institutions that routinely ship valuable and historic items
      through the mail. Although the Smithsonian Institution initiated some studies of
      the effect of electron beam irradiation on archived materials, little data
      existed on the effect that this process would have on forensic evidence.
      Approximately 97 different black, blue, red, green, and yellow writing inks were
      selected. Writing ink types included ballpoint, gel, plastic/felt tip, and
      rollerball. All noncontrol samples were subjected to standard mail irradiation
      conditions used by the U.S. Postal Service at the time this experiment was
      performed. A video spectral comparator and thin-layer chromatography (TLC)
      analysis were used to evaluate both the control and the irradiated samples. Some
      published studies reported changes in the presence/absence of dye bands in the
      chromatograms of irradiated writing inks. Some of these studies report the
      formation of additional dye bands on the chromatogram while others report missing
      dye bands. However, using standard testing guidelines and procedures, none of the
      97 irradiated inks tested were found to show any significant optical or chemical
      differences from the control samples. In addition, random testing of some of the
      ink samples using a second solvent system did not reveal any changes. However,
      one control ink did show some minor changes in optical properties and dye
      characteristics over time (but not TLC) while the irradiated sample remained
      stable. Significant changes in the ultraviolet fluorescence characteristics of
      the irradiated paper samples themselves (not inks) were also observed.

PMID- 17456089
TI  - Identification and comparison of electrical tapes using instrumental and
      statistical techniques: I. Microscopic surface texture and elemental composition.
AB  - Comparisons of polyvinyl chloride electrical tape typically rely upon evaluating
      class characteristics such as physical dimensions, surface texture, and chemical
      composition. Given the various techniques that are available for this purpose, a
      comprehensive study has been undertaken to establish an optimal analytical scheme
      for electrical tape comparisons. Of equal importance is the development of a
      quantitative means for sample discrimination. In this study, 67 rolls of black
      electrical tape representing 34 different nominal brands were analyzed via
      scanning electron microscopy and energy dispersive spectroscopy. Differences in
      surface roughness, calendering marks, and filler particle size were readily
      apparent, including between some rolls of the same nominal brand. The relative
      amounts of magnesium, aluminum, silicon, sulfur, lead, chlorine, antimony,
      calcium, titanium, and zinc varied greatly between brands and, in some cases,
      could be linked to the year of manufacture. For the first time, quantitative
      differentiation of electrical tapes was achieved through multivariate statistical
      techniques, with 36 classes identified within the sample population. A single
      blind study was also completed where questioned tape samples were correctly
      associated with known exemplars. Finally, two case studies are presented where
      tape recovered from an improvised explosive device is compared with tape
      recovered from a suspect.

PMID- 17456090
TI  - Analysis of condom lubricants for forensic casework.
AB  - The detection of DNA is inhibited in cases of sexual assault involving condom
      use. Trace evidence, including condom lubricant residues, provides crucial
      associative evidence in such cases. The existing Fourier transform infrared
      spectroscopy (FTIR) methods for lubricant analysis and detection are limited with
      regard to sensitivity and discrimination. The aim of this research was to
      establish a new method as an alternative to FTIR for the analysis of condom
      lubricant residues. Pyrolysis gas chromatography-mass spectrometry (PyGC-MS) and
      GC-MS are highly sensitive methods of analysis for a wide range of chemical
      substances. PyGC-MS and GC-MS were used to analyze condom lubricants in standard
      solution, from clean swabs and from postcoital swabs. Pyrolysis of
      polydimethylsiloxane (PDMS) lubricant forms cyclic products known as cyclic
      dimethyl siloxanes (DMS), which are separated and detected by the GC-MS. The
      polyethylene glycol (PEG) lubricant can be analyzed by GC-MS directly from
      solution. The methods of extraction and analysis presented in this paper were
      shown to be significantly more sensitive than FTIR for the analysis of PDMS and
      PEG condom lubricants. PDMS was detected as low as 1 mug in standard solution and
      from clean swabs using the PyGC-MS method. PEG was detected as low as 0.5 microg
      from standard solution and 50 mug from clean swabs using the GC-MS method.
      Unfortunately, we were unable to provide further discrimination between condom
      brands and subbrands. The methods established throughout the research were used
      successfully to detect condom lubricants from donated postcoital swabs.
      Lubricants were detected in abundance on swabs 12 h postcoitus. Recommendations
      are made regarding implementation of new methods for routine analysis of casework
      samples along with strict pyrolysis interpretation criteria to minimize the
      possibility of misinterpretation of false positives.

PMID- 17456091
TI  - Enhancement of ninhydrin- or DFO-treated latent fingerprints on thermal paper.
AB  - A new method for enhancement of ninhydrin or 1,8-diazafluoren-9-one (DFO)-treated
      latent fingerprints on thermal paper will be described. Most thermosensitive
      surfaces of thermal paper become dark when treated with DFO or ninhydrin
      petroleum ether (NPB) solution. This effect minimizes contrast between the
      developed fingerprints and the background. The new method described reduces this
      dark staining without removing the thermosensitive layer and parts of the
      developed fingerprints, as occurs with acetone washing. Through the new method,
      the developed fingerprints appear in sharp lines and high contrast. Extensive
      tests were performed, leading to an optimized working solution, which charges the
      paper with a minimum of chemicals, is cheap, and enables a large quantity of
      papers to be treated in a short time. The working solution contains commercially
      available, nonvolatile, nitrogenous organic compounds and can be used like the
      application of NPB solution by dipping.

PMID- 17456092
TI  - Comparison of motor oils using high-temperature gas chromatography-mass
      spectrometry.
AB  - The analysis of motor oils has wide applications in the forensic science field
      from comparing lubricants transferred between an automobile and a victim or crime
      scene to differentiating the compositions of plastic explosives. In this study,
      40 unused motor oils were analyzed and compared by high-temperature gas
      chromatography-mass spectrometry to determine the potential for oil
      individualization. Oil samples were also collected from the crankcase dipsticks
      of 30 cars. Twenty-six of these oils could be differentiated from each other
      based on visual comparisons of the unresolved envelope (baseline rise due to
      incomplete separation) and the resolved hydrocarbons in the raw total ion
      chromatograms (TICs) and smoothed TIC data. Four of these oils were analyzed as
      unknowns and were correctly related to the corresponding vehicle. The use of
      extracted ion profiles (EIPs) was explored as a means to further discriminate
      between the indistinct samples based on the polycyclic aromatic hydrocarbon (PAH)
      content. The research discussed in this paper demonstrated that differentiation
      of motor oils was possible by examining the TIC, smoothed TIC, and EIP data.

PMID- 17456093
TI  - Y-STRs in forensic medicine: DNA analysis in semen samples of azoospermic
      individuals.
AB  - The incidence of rape has increased, especially in metropolitan areas, such as
      the city of Sao Paulo. In Brazil, studies about it have shown that the majority
      of this type of crime is committed by the relatives and persons close to the
      victim. This has made the crime more difficult to be denounced, as only 10% of
      the cases are reported to competent police authorities. Usually, cytological
      exams are carried out in sex crime investigations. The difficulty in showing the
      presence of spermatozoa is frequent, but it does not exclude the presence of male
      DNA. The absence of spermatozoa in material collected from rape victims can be
      due to several factors, including the fact that the agressor suffers from
      azoospermia. This condition can be the result of a successful vasectomy. As the
      majority of DNA in the ejaculation sample is from spermatozoa, there is much less
      DNA to be analyzed. This study presents the application of Y-STRs (DYS19,
      DYS389I, DYS389II, DYS390, DYS391, DYS392, and DYS393) in DNA analysis of sperm
      samples from 105 vasectomized men. The study demonstrated a great variation in
      DNA concentration. DNA extraction and amplification was possible in all sperm
      samples even in the absence of spermatozoa. The same profile was observed, for
      each individual, from DNA extracted from blood, pre- and postvasectomy semen
      samples. The use of markers specific for Y chromosome in sex crime cases,
      especially in the absence of spermatozoa, is very important, mainly because in
      most situations there is a small quantity of the agressor's DNA in the medium and
      a large quantity of the victim's DNA.

PMID- 17456094
TI  - Age estimation of Korean adults by occlusal tooth wear.
AB  - The aim of the present study was to evaluate the validity of the modified Kim's
      scoring system as a practical method of recording occlusal tooth wear and
      estimating age. For this purpose, 1092 pairs of maxillary and mandibular full
      arch casts were randomly selected, scored, and analyzed. The results showed that
      the modified Kim's scoring system had excellent reliability, and that occlusal
      tooth wear had a positive correlation with age. Tooth wear scores of all teeth
      except the two lower central incisors were higher in males than in females.
      Calculating tables for age estimation were designed by multiple linear regression
      analysis. Estimated ages were within +/-5 years of actual ages in 63.5% of male
      subjects, and 64.0% of female subjects. The accuracy of age estimation was
      increased when the subjects were divided into two age groups and data were re
      analyzed. Collectively, it was shown that the modified Kim's scoring system is a
      reliable and accurate method for age estimation, and that the data from these
      1092 individuals can be used as a standard for age estimation of Korean adults.

PMID- 17456095
TI  - Forensic dental training in the dental school curriculum.
AB  - This article reviews the literature regarding forensic education in the dental
      school curriculum and describes an exercise in forensic identification of victims
      of a mass casualty. Radiographs were made of dentate human cadavers in the gross
      anatomy laboratory at the Southern Illinois School of Dental Medicine. The jaws
      were then removed to provide "wet specimens" for the exercise. Several
      restorations were performed on the cadaver teeth, after which radiographs of the
      dissected jaws were made. One author wrote up mock dental records for each of the
      victims. These records included the first set or "premortem" radiographs.
      Students participating in the exercise were provided with a plane crash scenario,
      the dental records of the passengers on the manifest, the dissected jaws, and the
      second set or "postmortem" radiographs. Students were expected to form three
      teams. The first two teams evaluated the ante-mortem and postmortem dental
      records. The third team compared the ante-mortem and postmortem records to arrive
      at identification. The purpose of the exercise was twofold. It introduced dental
      students to forensic dentistry and emphasized the need for complete and accurate
      record keeping in the dental office. Several factors lessened the realism of the
      exercise and made it difficult to reproduce in the future. These included the
      uniformity of the dental records and the destruction of cadaver material
      following the exercise.

PMID- 17456096
TI  - Development and validation of a human bitemark severity and significance scale.
AB  - Numerous efforts have been made to develop a consistent manner to describe bite
      injuries. Some have been related to the type of injury, others to the manner in
      which it was caused or simply its anatomical location. Bitemark severity is
      related to forensic significance and hence the ability to use a common means of
      injury description would be of benefit to odontologists and those who commission
      their services. A novel index, relating severity to forensic significance, was
      developed. A text version and accompanying visual index were produced and
      distributed (via the web) to three groups: odontologists, forensic pathologists,
      and police officers. A total of 35 bitemarks were assessed and rated using the
      new index. Weighted kappa analyses were used to determine the agreement data both
      between and within groups and individuals. kappa demonstrated a high level of
      intraoperator and interoperator reliability, particularly in the police officer
      group. The index shows promise as a universal means of describing bite injuries
      between professionals concerned with their detection and analysis.

PMID- 17456097
TI  - Review of pathologic findings in remnant hearts following valve donation.
AB  - The failure of medical examiners/coroners (ME/C) to allow heart valve donation is
      a major problem encountered by tissue agencies. Even though many ME/C favor
      tissue donation they remain responsible for determination of cause and manner of
      death. In 2001, the Jesse E. Edwards Registry of Cardiovascular Disease was
      approached by one of the nation's largest tissue procurement agencies (The
      American Red Cross--ARC) for the purpose of performing cardiovascular pathologic
      examinations following valve donation. The affiliation existed from October 2001
      to January 2005. This study was undertaken to review all 593 postvalve recovery
      heart remnants received during that time period to tabulate the abnormalities
      identified and to determine whether donation interfered with the determination of
      cause of death. For each case, a preliminary cause of death was provided by the
      ARC. The decedent's body height and weight were also provided. Using the
      preliminary cause of death, the 593 cases were divided into natural and
      nonnatural manner of death groups. This division of the cases resulted in 106
      cases placed in the natural manner of death group and 487 cases in the nonnatural
      manner of death group. For each case, all cardiac findings including significant
      conditions, additional findings, incidental findings, and congenital
      abnormalities were tabulated. Within the natural manner of death group, 15 cases
      had a noncardiac cause of death and 91 cases had a cause of death suspected to be
      cardiac related. In the 91 cases, a total of 132 significant cardiac findings
      were identified and there were six structurally normal hearts including two
      infants. In the nonnatural manner of death group, 214 significant cardiac
      findings were identified and 222 cases had a structurally normal heart. In both
      natural and nonnatural groups, the most common cardiac abnormality was
      atherosclerotic coronary artery disease. Other frequently encountered conditions
      were also identified including 11 cases with acute angle of origin of a coronary
      artery (five cases natural group; six cases nonnatural group). An important
      feature of this review was the recognition of potentially inheritable conditions
      that were diagnosed in both natural and nonnatural manner of death groups. There
      were three cases of hypertrophic cardiomyopathy (one natural; two nonnatural),
      three cases of arrhythmogenic right ventricular cardiomyopathy (one natural; two
      nonnatural), and one case of mitral valve prolapse (natural). In reviewing these
      cases, we did not feel that valve donation severely impaired cardiac pathologic
      examination. The benefits of cardiovascular pathologic examination by a cardiac
      pathologist include the identification of significant and incidental findings and
      recognition of potentially inheritable conditions.

PMID- 17456098
TI  - Importance of electromyography and the electrophysiological severity scale in
      forensic reports.
AB  - Forensic reports on traumatic peripheral nerve injuries include dysfunction
      degrees of extremities, which are arranged according to the Turkish Penalty Code.
      The aim of this study is to discuss the role and importance of electromyography
      while preparing forensic reports in the cases of traumatic peripheral nerve
      injuries and the usefulness of scoring systems. A modified global scale,
      recommended by Mondelli et al., was used to assess the electrophysiological
      impairment of each peripheral nerve. Forensic reports of 106 patients, reported
      between 2002 and 2004, were evaluated. Thirty-four percent of the cases were
      reported as "total loss of function," 41.5% were reported as "functional
      disability," and there were no dysfunctions in the other cases in forensic
      reports that were prepared based on Council of Social Insurance Regulations of
      Health Processes and Guide prepared by the Council of Forensic Medicine and
      profession associations of forensic medicine. When we rearranged these forensic
      reports based on the electrophysiological severity scale (ESS), it was clearly
      found that all of the score 2 cases and 86.7% of the score 3 cases corresponded
      to "functional disability" and 91.4% of the score 4 cases correspond to "total
      loss of function." We found a significant correlation between the ESS and
      functional evaluation in peripheral nerve injury cases. Evaluation of functional
      disabilities in peripheral nerve injuries with the ESS represents a standardized
      and objective method used for forensic reports.

PMID- 17456099
TI  - Traumatic asphyxia in weightlifters.
AB  - The cases presented here are an unrecognized source of accidental asphyxia-
      compression of the neck by barbells. Two cases of traumatic asphyxia due to this
      preventable hazard occurred in a 5-year period in central New York. There have
      been at least 11 similar deaths reported to the United States Consumer Product
      Safety Commission (CPSC) and cataloged in the National Electronic Injury
      Surveillance System between 1999 and 2002. A petition filed in 2003 with the CPSC
      proposed mandatory labeling of bench presses to make consumers aware of this
      hazard, but was denied. This report looks at the deaths that have occurred due to
      this unrecognized safety threat and provides pertinent advice to make bench
      pressing a safer activity.

PMID- 17456100
TI  - Accidental boric acid poisoning following the ingestion of household pesticide.
AB  - Borate-containing compounds were formerly used as topical antiseptics and were
      components of many medicinal preparations including skin powders and ointments
      used for the treatment of burns and diaper rash. These compounds were also used
      as irrigants for body cavities, including the pleural, vaginal, and rectal
      cavities. These applications were subsequently discontinued by the medical
      community when the toxicity and potential lethality of borates were recognized.
      Although documented cases of borate poisoning are now rare, the chemical is still
      an active component commonly used in high concentrations in household
      disinfectants/cleaners, pesticides, and wood preservatives. While the majority of
      documented borate-related deaths have occurred in infants, the toddler population
      is currently at risk due to possible exposure to these household products. We
      present the case of an 18-month-old child who died following the accidental
      ingestion of a boric acid-containing, commercially available roach pesticide
      product.

PMID- 17456101
TI  - Appearance of chemical burns resulting from the washing of a deceased body with
      bleach.
AB  - The authors report on a case of postmortem washing of a body with bleach. An
      adult female victim was found nude in an alleyway with both hands removed in the
      City of Westminster, CO. Cause of death was attributed to severe blunt force
      trauma to the head. The victim had been dumped in the alleyway within 7 h of
      discovery. Evidence discovered at the crime scene and autopsy indicated that the
      murder and subsequent washing of the body with bleach occurred at a secondary
      location(s). The victim was wet to the touch, presenting a strong odor of bleach.
      Several "ribbon"-like burn patterns were observed on the victim's back and upper
      thighs. These burn marks were replicated by dowsing a deceased pig with an over
      the-counter concentration of bleach.

PMID- 17456102
TI  - Psychological adjustment in a forensic sample: relationship with approach- and
      avoidance-coping typologies.
AB  - Most studies that relate coping strategies with psychological symptoms usually
      consider a single coping dimension. This means that interpretation of the results
      is unclear and only partially true as subjects activate different types of coping
      strategies simultaneously when faced with a stressor. The objective of the
      present study is to analyze the relationships between coping and psychopathology
      in young inmates, taking into account the number of approach and avoidance
      answers simultaneously. The results show that the inmates with above-average
      scores in avoidance coping and below average in those of approach (coping
      responses inventory--adult form, [CRI-A]) show higher symptomatology (MMPI-2)
      than the inmates who obtain above-average scores in both avoidance and approach
      strategies. It can be deduced that it is not the high use of avoidance coping
      that is related to psychopathology, but rather the combined use of many avoidance
      strategies and few approach strategies. The convenience of jointly taking into
      account both types of coping is discussed.

PMID- 17456103
TI  - Detection of malingered PTSD: an overview of clinical, psychometric, and
      physiological assessment: where do we stand?
AB  - Posttraumatic stress disorder (PTSD) is a condition that can be easily malingered
      for secondary gain. For this reason, it is important for physicians to understand
      the phenomenology of true PTSD and indicators that suggest an individual is
      malingering. This paper reviews the prevalence of PTSD for both the general
      population and for specific events, such as rape and terrorism, to familiarize
      evaluators with the frequency of its occurrence. The diagnostic criteria for
      PTSD, as well as potential ambiguities in the criteria, such as what constitutes
      an exposure to a traumatic event, are reviewed. Identified risk factors are
      reviewed as a potential way to help differentiate true cases of PTSD from
      malingered cases. The question of symptom overreporting as a feature of the
      disease versus a sign of malingering is discussed. We then examine how the
      clinician can use the clinical interview (e.g., SIRS, CAPS), psychometric
      testing, and the patient's physiological responses to detect malingering.
      Particular attention is paid to research on the MMPI and the subscales of
      infrequency (F), infrequency-psychopathology (Fp), and infrequency-posttraumatic
      stress disorder (Fptsd). Research and questions regarding the accuracy of self
      report questionnaires, specifically the Mississippi Scale (MSS) and the
      Personality Assessment Inventory (PAI), are examined. Validity, usability, and
      cutoff values for other psychometric tests, checklists, and physiological tests
      are discussed. The review includes a case, which shows how an individual used
      symptom checklist information to malinger PTSD and the inconsistencies in his
      story that the evaluator detected. We conclude with a discussion regarding future
      diagnostic criteria and suggestions for research, including a systematic
      multifaceted approach to identify malingering.

PMID- 17456104
TI  - A case of stalking in the workplace and subsequent sexual homicide.
AB  - A case of stalking in the workplace and subsequent sexual homicide by a 33-year
      old male is reported. Following several months of stalking a 38-year-old female,
      the male subject went to the woman's office after business hours and restrained,
      raped, and murdered her. The cause of death was multiple stab wounds. The facts
      of the case reveal that the subject fits a predatory-type stalker, which
      represents a small subgroup within stalkers that has received little attention.
      Unlike other types of stalkers, the predatory stalker gives little warning to
      their victim (or multiple victims), as their stalking behaviors tend not to be
      very invasive or harassing. In general, most stalkers are not physically violent;
      however, predatory-type stalkers, given their tendency for sexual violence, are
      dangerous and the importance of identifying them is emphasized. Factors
      associated with perpetrators of sexual homicide are discussed.

PMID- 17456105
TI  - Diary of an astronaut: examination of the remains of the late Israeli astronaut
      Colonel Ilan Ramon's Crew Notebook recovered after the loss of NASA's space
      shuttle Columbia.
AB  - Two months after the fatal re-entering into the Earth's atmosphere of Columbia
      flight STS-107, the remains of Israeli astronaut Colonel Ilan Ramon's Crew
      Notebook were found strewn in a field in San Augustine County, TX. The random
      pile of papers was found to have survived the calamity of the Shuttle's
      disintegration remarkably well. Most of the papers recovered were torn and/or
      washed out to varying degrees but only mildly charred around the edges. The
      sheets of paper could be categorized into four groups: Group I: eight sides of
      paper written while in space in black ink and in pencil--Ramon's personal diary;
      the writing on these eight sides of paper survived well and is only missing where
      the pages were torn. Small fragments found in the field were physically matched
      to holes in the pages thus locating their original positions in the text. Group
      II: six sides of technical preparation notes written by Ramon before the mission.
      The writing on these pages was washed out entirely, but much of it was visualized
      using infrared luminescence. Group III: eight sides of personal notes prepared by
      Ramon before the mission written in blue ink. The writing on these pages was
      barely visible to the naked eye and not visualized by infrared luminescence, but
      was made largely legible by digital enhancement imaging. Group IV: a few sides of
      printed technical information. These pages were mostly intact and were not
      examined at length as they contained standard printed material. After completion
      of examinations at the Questioned Document Laboratory of the Israel Police, the
      diary was transferred to the Paper Conservation Department of the Israel Museum
      for preservation and strengthening treatments.

PMID- 17456106
TI  - Letter to the editor--a preliminary investigation of siblicide as a function of
      genetic relatedness.

PMID- 17456107
TI  - The use of Polilight in the detection of seminal fluid, saliva, and bloodstains
      and comparison with conventional chemical-based screening tests. J Forensic Sci
      2006;51(2):361-70.

PMID- 17456109
TI  - Elemental analysis of human cremains using ICP-OES to classify legitimate and
      contaminated cremains. J Forensic Sci 2006;51(5):967-73.

PMID- 17456116
TI  - Y-chromosomal STR haplotypes in two endogamous tribal populations of Karnataka,
      India.
AB  - POPULATION: Approximately 5.0 mL of blood sample was collected from a total of
      150 men belonging to two tribal populations of coastal Uttar Kannada district of
      Karnataka, with their informed written consent. Both the populations are
      endogamous and they belong to the Dravidian linguistic family. Halakki is a
      tribal group having a population size of c. 3383. They claim that they originally
      belong to Gujarat and Rajasthan, and migrated through Andhra Pradesh to
      Karnataka. Kunabhi is also a tribal population, c. 35,214 in number. They were
      hunters and gatherers but presently they practice agriculture.

PMID- 17456117
TI  - Genetic polymorphism of two novel STR loci AY639920 and AY639923 in a Chinese
      population.

PMID- 17456118
TI  - Twelve-locus Y-STR haplotypes in the Flemish population.
AB  - POPULATION: One hundred and thirteen unrelated Flemish men from Belgium.

PMID- 17456119
TI  - Allele frequencies of D16S764 and D10S2470 in two populations.

PMID- 17456121
TI  - Getting on the bandwagon.

PMID- 17456122
TI  - Perceived benefits on family health of small groups for families with children.
AB  - BACKGROUND: Thus far, international research on small groups has focused on
      health problems. Research on preventive, resource-, and family-oriented small
      groups and their impact on family health is scant. OBJECTIVES: To describe the
      experiences of families with small children concerning resource-enhancing small
      support groups, and to identify the benefits to family health described by
      participating parents at the end of the group processes. SAMPLE: The study
      population consisted of parents (n=123) attending 13 small groups. Participants
      included 63 mothers and 14 fathers (63% response rate). METHODS: Data were
      collected through group interviews. Qualitative content analysis of latent
      content was the method of analysis. RESULTS: Small groups provided the parents
      with knowledge about family life and encouraged them to seek information, made
      them feel refreshed, strengthened their social support networks, enhanced their
      awareness of their own resources and the different developmental needs at times
      of change in the family, and increased their confidence concerning their ability
      to cope. CONCLUSIONS: Concepts from this study can be used in the future to
      construct instruments to evaluate the effectiveness of small groups from the
      perspective of families and family health. The findings add to our professional
      understanding of resource-oriented family work from the perspective of families.

PMID- 17456123
TI  - Body mass index and intake of selected foods in African American men.
AB  - BACKGROUND: There are minimal data on the relationship between dietary
      consumption of fats, vegetables, and fruits and body mass index (BMI) in African
      American men. OBJECTIVE: This study tested the relationships between selected
      dietary consumption and BMI. DESIGN: The sample was a community-based cohort of
      204 African American Southern men who attended a free prostate cancer educational
      and screening program. The screening was part of an all-day African American
      celebration that included a health fair. Diet was assessed with a Brief Dietary
      Scale for Selected Food Intake and Preparation. RESULTS: Most of the men were
      overweight (34%) or obese (47%). The majority of men ate their chicken (90%) and
      fish (96%) fried. Few men ate vegetables at supper (29.4%) or lunch (15.8%).
      Three fatty food items were significantly associated with BMI: leaving the
      chicken skin on chicken (p=.03); intake of low-fat or skim milk (p=.02); and
      cooking vegetables with butter (p=.03). CONCLUSION: African American men need
      culturally appropriate dietary interventions to reduce obesity.

PMID- 17456124
TI  - Effect of reading additional safety information on planned use of over-the
      counter analgesics.
AB  - OBJECTIVES: This study was used to test the effect on planned safe use of over
      the-counter (OTC) analgesics of adding information about the potential for
      nonsteroidal anti-inflammatory drug (NSAID) interaction with antihypertensive
      medications, the potential for interaction of alcohol and acetaminophen, and
      NSAID ceiling effects to the Federal Drug Administration's (FDA's) OTC analgesics
      pamphlet. DESIGN: A randomized posttest-only double-blind experimental design was
      used to test an intervention with a comparison group reading the FDA pamphlet,
      and treatment group reading the pamphlet with added information. SAMPLE:
      Participants included 137 adults. INTERVENTION: Participants read the treatment
      or the comparison pamphlet. RESULTS: Both groups responded with similar planned
      use of OTC analgesics. The majority were likely to read the label before taking
      an OTC analgesic, but were unlikely to give acetaminophen to a family member
      using antihypertensive medication. CONCLUSIONS: Reading additional information
      about OTC analgesics resulted in no greater intention to safely use analgesics.
      Responses indicated reluctance to use OTC analgesics, and the potential need for
      increased health teaching regarding use of OTC analgesics with antihypertensive
      medication. Public health teaching should include the importance of treating pain
      and selecting the safest OTC analgesics for the clinical situation.

PMID- 17456125
TI  - Addressing mental health and stress in Medicaid-insured pregnant women using a
      nurse-community health worker home visiting team.
AB  - OBJECTIVE: To describe the conceptual framework and program features of a nurse
      community health worker (CHW) team home visiting intervention, the trial design
      to test the program, and the results of a comparative evaluation of prenatal
      program participation. DESIGN: In the context of a community-based, randomized
      trial, we compared participation in a nurse-CHW team intervention with the
      standard community care that included a state Medicaid program (enhanced prenatal
      services) with nurse home visiting. SAMPLE: Medicaid-eligible pregnant women
      (n=530), who maintained their pregnancies, had a live birth, retained custody of
      the child, completed more than an enrollment assessment, did not move out of the
      county, and were not lost to follow-up. MEASUREMENTS: Provider reports of face-to
      face prenatal contacts and demographic and psychosocial risk assessments obtained
      at study enrollment. RESULTS: Significant differences in the number of women with
      prenatal program contact and the total amount of contact were found, favoring the
      nurse-CHW team approach. More women with risk characteristics were reached in the
      nurse-CHW team group, with the exception of women with alcohol and drug use
      risks. CONCLUSIONS: A nurse-CHW team approach demonstrated advantage in reaching
      women who had barriers to participation and delivering more intensive services.

PMID- 17456126
TI  - Education in a homeless shelter to improve the nutrition of young children.
AB  - OBJECTIVE: To improve the nutritional status of homeless children by implementing
      an educational program for their mothers and the cafeteria staff at a homeless
      shelter. DESIGN: Program evaluation including before and after measures of
      mothers' nutritional knowledge and nutritional quality of foods served in the
      cafeteria. SAMPLE: Fifty-six mothers with children aged 18 months to 6 years and
      3 cafeteria staff. INTERVENTION: Four nutrition classes developed by a registered
      nutritionist were taught to mothers by clinic nurses; 3 nutrition classes were
      taught to the cafeteria staff by the nutritionist. RESULTS: Mothers scored higher
      on posttests than on pretests, indicating improved nutritional knowledge. Minimal
      differences in the nutritional quality of foods served to residents were observed
      after staff education. CONCLUSIONS: This project demonstrates the challenges of
      altering the nutritional status of children in a homeless shelter. Despite
      mothers showing better knowledge of nutritional requirements for children, the
      types of food served in the cafeteria were an obstacle to them in practicing what
      they had learned. The cafeteria staff's ability to demonstrate their learning was
      impeded by the constraints of food donations. Educational strategies may need to
      be augmented by policies to improve the nutritional status of children in
      homeless shelters.

PMID- 17456127
TI  - A formative evaluation to develop a school health nursing early intervention
      model for adolescent substance use.
AB  - OBJECTIVE: To improve an early intervention (EI) triggered by the Adolescents'
      Substance Use Measurement (ADSUME) as a method to prevent substance abuse among
      adolescents. We assessed how ADSUME and EI work in practice and how EI could be
      improved. DESIGN AND SAMPLE: School health nurses (n=10) tested ADSUME and EI on
      14- to 18-year-old adolescents (n=228). Six months later, these nurses and their
      professional partners were invited to assess EI in focus group interviews.
      METHODS: Four focus group interviews involving a total of 24 nurses and partners
      were implemented. Interview data were analyzed with qualitative content analysis.
      RESULTS: ADSUME concretized assessment, activated profound dialogue, and proved
      to be an important part of EI. It was important to assess the adolescent's
      resources in addition to the ADSUME score. EI worked well in confidential
      dialogues after the adolescent and the PHN reached a consensus on the level of
      concern about the adolescent's substance use. The recommended EI enabled
      individual brief intervention in all four stages of substance use, from
      abstinence or experimental use to hazardous use. CONCLUSIONS: EI was improved
      practically, and the contents of the intervention were reformulated. It is
      important to integrate EI with the preventive efforts of the school.

PMID- 17456128
TI  - Using a community-based outreach program to improve breast health awareness among
      women in Hong Kong.
AB  - OBJECTIVE: To evaluate the effectiveness of a community-based health education
      program via a mobile van to promote the awareness of breast cancer and breast
      self-examination (BSE) practice among women in Hong Kong. DESIGN: One group
      pretest/posttest design. SAMPLE AND MEASUREMENTS: Seven hundred and seventy-seven
      women in Hong Kong completed a self-administered questionnaire before and after a
      breast health education program from May 2002 to March 2003. RESULTS: About half
      were aware of breast health and breast diseases (53.7%) and breast screening
      methods (48.6%) before the intervention. It was found that women who had received
      instruction on BSE practice, and those who were aware of breast screening
      methods, breast health, and breast diseases were more likely to have had prior
      BSE practice. Most indicated their willingness to practice BSE regularly (93.3%)
      and to pass on the BSE knowledge to their relatives and friends (92%) in the
      posttest. CONCLUSIONS: The outreach health education program has successfully
      reached women living in the 18 districts in Hong Kong. It appears to be useful in
      raising the awareness of breast health and BSE practice among the women, but
      longer term follow-up is required to ascertain its sustainability.

PMID- 17456129
TI  - Relationship between personality traits, job satisfaction, and job involvement
      among Taiwanese community health volunteers.
AB  - OBJECTIVE: To understand the relationship between job involvement, job
      satisfaction, and personality traits among health volunteers in one Taiwan
      community. It is not easy to retain voluntary workers as part of health programs
      even though they have been trained. Previous research has shown that in order to
      increase job involvement, volunteers must effectively fulfill their needs to
      achieve and obtain job satisfaction. DESIGN AND SAMPLE: Cross-sectional design.
      Surveys were mailed to 317 health volunteers at community health centers in I-lan
      County, northern Taiwan; 213 complete responses (67%) were received. METHODS: The
      survey instrument included sociodemographic items and scales measuring locus of
      control, achievement orientation, job involvement, and job satisfaction. RESULTS:
      Most respondents (94.8%) were female and their average age was 49.6 years. In
      terms of personality traits, most volunteers showed internal control orientation.
      Explainable variance for the prediction of job involvement from a combination of
      participation frequency, on-job training, achievement orientation, and job
      satisfaction was 33.6%. CONCLUSIONS: The results suggest that there is a need to
      strengthen cooperative relationships among volunteers by initiating well-planned
      volunteer training programs and growth groups. These should involve the
      empowerment concept with the aim of enhancing the volunteers' interpersonal
      relationships and job satisfaction.

PMID- 17456130
TI  - Study of the reliability and validity of the Community Health Intensity Rating
      Scale (CHIRS) in the Turkish community.
AB  - The purpose of this study was to examine the reliability and validity of the
      Community Health Intensity Rating Scale (CHIRS) that was translated into the
      Turkish language and applied in the Turkish community. The CHIRS is a tool that
      assesses the intensity of need for care of persons/families in the community. The
      original version of the tool was translated into Turkish, examined for face
      validity and language appropriateness by the Turkish experts, and then applied to
      372 families living in Odemis, Turkey. Significant correlations were found
      between total scale score (TSS) and total number of household members, and
      between the TSS and the total number of visits to any health institution within
      the previous month. In addition, the self-health care needs evaluation scores
      supported predictive validity. For reliability, min-max values, standard errors
      and deviations, skewness, and kurtosis coefficients of parameter scores, domain
      scores, and TSS were examined. The mean TSS was 26.7 (+/- 5.32) and the mean age
      of the participants was 35.0 years. For internal consistency, Cronbach's alpha
      (.525) and Guttman split-half coefficient (.629) values were established for the
      TSS. In conclusion, the reliability and validity of the Turkish version of CHIRS
      have been established.

PMID- 17456131
TI  - For the good of a common discipline. 1931.
AB  - This historical commentary reprints excerpts from Mary Sewall Gardner's January
      1, 1931, editorial in the original Public Health Nursing journal. Gardner (1871
      1961) directed the Providence District Nursing Association until her retirement
      in 1931. She had also served as president of the National Organization for Public
      Health Nursing. In her editorial, Gardner sought to relieve the sense of
      hopelessness caused by the deepening Depression and ameliorate the fear that
      public health nursing advances had been reversed. An introduction to the impact
      of the Great Depression on working classes and its impact on organizations
      responsible for visiting nurses provides the background to help evaluate
      Gardner's intent. Her words find parallels in the inaugural address of Franklin
      Delano Roosevelt in 1933. This suggests that the pervasive crisis produced a
      distinctive tone and perspective of interdependence and mutual resolve that
      leaders used to help their followers through troubling times.

PMID- 17456132
TI  - Tissue Doppler imaging analysis at precardioversion time may be a useful marker
      to identify a subgroup of patients with increased risk for atrial fibrillation
      recurrence.

PMID- 17456134
TI  - Focal atrial tachycardia originating from the left atrial appendage:
      electrocardiographic and electrophysiologic characterization and long-term
      outcomes of radiofrequency ablation.
AB  - INTRODUCTION: This study sought to investigate electrophysiologic characteristics
      and radiofrequency ablation (RFA) in patients with focal atrial tachycardia (AT)
      arising from the left atrial appendage (LAA). METHODS: This study included seven
      patients undergoing RFA with focal AT. Activation mapping was performed during
      tachycardia to identify an earlier activation in the left atria and the LAA. The
      atrial appendage angiography was performed to identify the origin in the LAA
      before and after RFA. RESULTS: AT occurred spontaneously or was induced by
      isoproterenol infusion rather than programmed extrastimulation and burst atrial
      pacing in any patient. The tachycardia demonstrated a characteristic P-wave
      morphology and endocardial activation pattern. The P wave was highly positive in
      inferior leads in all patients. Lead V1 showed upright or biphasic (+/-)
      component in all patients. Lead V2-V6 showed an isoelectric component in five
      patients or an upright component with low amplitude (<0.1 mV) in two patients.
      Earliest endocardial activity occurred at the distal coronary sinus (CS) ahead of
      P wave in all seven patients. Mean tachycardia cycle length was 381 +/- 34 msec
      and the earliest endocardial activation at the successful RFA site occurred 42.3
      +/- 9.6 msec before the onset of P wave. RFA was acutely successful in all seven
      patients. Long-term success was achieved in seven of the seven over a mean follow
      up of 24 +/- 5 months. CONCLUSIONS: The LAA is an uncommon site of origin for
      focal AT (3%). There were consistent P-wave morphology and endocardial activation
      associated with this type of AT. The LAA focal ablation is safe and effective.
      Long-term success was achieved with focal ablation in all patients.

PMID- 17456135
TI  - Resynchronization or dyssynchronization--successful treatment with biventricular
      stimulation of a child with obstructive hypertrophic cardiomyopathy without
      dyssynchrony.
AB  - We present a case of a 10-year-old boy with hypertrophic cardiomyopathy,
      intraventricular pressure gradient of 104 mmHg, and indications for prophylactic
      ICD implantation. Based on intraoperative pressure measurements, the child was
      implanted with biventricular ICD. During 2.5 months of observation, the patient's
      functional status improved significantly, as shown by subjective and objective
      parameters and, moreover, the pressure gradient fell to 12 mmHg. Significant
      electrical and mechanical cardiac dyssynchrony appeared parallel to clinical
      improvement.

PMID- 17456136
TI  - Pilsicainide-induced ventricular tachycardia originating from right ventricular
      outflow tract.

PMID- 17456137
TI  - Gene therapy for cardiac arrhythmias: a dream soon to come true?
AB  - Alternatively, excitement and frustration have been generated from the literature
      reports of gene therapy for treatment and potential cure of cardiac diseases. The
      time since the first literature report of in vivo myocardial gene transfer is
      more than 15 years, and the time since the first report of gene therapy for a
      cardiac arrhythmia is six years. Clinical trials, let alone clinical usage, of
      these promising therapies have not yet started. This article reviews the current
      state of the art for arrhythmia gene therapy, including the literature reports of
      antiarrhythmic studies and of problems within the field. Gene transfer continues
      to be a promising technology, but patience is required as these problems are
      solved and the therapies make their way through the preclinical and clinical
      testing process.

PMID- 17456138
TI  - Venice Chart international consensus document on atrial fibrillation ablation.

PMID- 17456140
TI  - Towards an integrated approach in supporting microbiological food safety
      decisions.
AB  - Decisions on food safety involve consideration of a wide range of concerns
      including the public health impact of foodborne illness, the economic importance
      of the agricultural sector and the food industry, and the effectiveness and
      efficiency of interventions. To support such decisions, we propose an integrated
      scientific approach combining veterinary and medical epidemiology, risk
      assessment for the farm-to-fork food chain as well as agricultural and health
      economy. Scientific advice is relevant in all stages of the policy cycle: to
      assess the magnitude of the food safety problem, to define the priorities for
      action, to establish the causes for the problem, to choose between different
      control options, to define targets along the food chain and to measure success.

PMID- 17456141
TI  - Long-lasting stability of vaccinia virus (orthopoxvirus) in food and
      environmental samples.
AB  - Poxviruses are known to remain infectious in the scabs of patients for months to
      years. The aim of this study was to investigate viral stability in storm water,
      food or gauze spiked with vaccinia virus strain Munich 1 (VACV M1). Storm water,
      storm water supplemented with either fetal calf serum (FCS) or potting soil was
      stored at two different temperatures (refrigerator, room temperature; 4 degrees
      C/25 degrees C). In addition, we analysed the viability of VACV M1 on the surface
      of bread, salad, sausages and gauze bandages stored at 4 degrees C. Samples were
      titrated in MA 104 cells and the presence of viral DNA was demonstrated by
      orthopoxvirus-specific PCRs. After 2 weeks, reisolation of VACV M1 from all kinds
      of food, bandage and water samples except for storm water supplemented with
      potting soil was possible. Viral DNA was detected in almost all samples by PCR.
      Prolonged experiments with VACV M1-spiked storm water and storm water
      supplemented with FCS revealed that samples kept at 4.5 degrees C are infectious
      for up to 166 days. Our data demonstrate that VACV M1 has a longlasting stability
      in water and food. The results obtained during this study should be taken into
      account for risk assessment calculations for poxvirus transmission. Implying that
      variola virus and vaccinia virus behave in a similar way, our data call for
      sophisticated countermeasures in cases of a variola release in biological
      warfare.

PMID- 17456142
TI  - Application of peracetic acid and quarternary ammonium disinfectants as a part of
      sanitary treatment in a poultry house and poultry processing plant.
AB  - Hygiene and sanitation play a major role in any effective disease control
      programme for poultry production and processing premises. Various deficiencies in
      disinfection may induce that chains of infections are not broken from one stock
      to another. The present study investigated the efficacy of disinfection on a
      broiler farm and in a plant processing poultry from the investigated farm.
      Besides inspection of disinfection, the influence of contamination on broiler
      carcasses and consequences of this contamination on sanitation of the processing
      lines were studied. Swabs from surfaces coming into contact with the handled raw
      material were taken and evaluated. The results obtained by a standard
      microbiological swab method were evaluated and compared with an ATP
      bioluminescence method. The investigations included determination of total counts
      of microorganisms, coliform bacteria and moulds. When employing the standard
      plate-count method, the total counts of microorganisms (TCM) reached <1, 1-100
      and >100 CFU in 0, 12 and 88% swabs on poultry farm and in 22%, 36% and 42% swabs
      in the processing plant, respectively. The bioluminescence method was used only
      in the processing plant and contamination corresponding to <100, 100-300 and >300
      relative light units (RLU) was detected in 80%, 10% and 10% swabs respectively.

PMID- 17456143
TI  - First diagnosis of Encephalitozoon intestinalis and E. Hellem in a European brown
      hare (Lepus europaeus) with kidney lesions.
AB  - Encephalitozoon intestinalis and Encephalitozoon hellem were diagnosed in the
      kidneys of a free-ranging European brown hare (Lepus europaeus) with multifocal
      wedge-shaped chronic interstitial nephritis using real-time PCR and microarray.
      This is the first description of these microsporidia species in a European brown
      hare, which are both potential zoonotic agents.

PMID- 17456144
TI  - Seroprevalence of antibodies to Neospora caninum in urban and rural dogs in north
      west Italy.
AB  - Sera were collected from 490 dogs from north-west Italy. One hundred and eighty
      eight dogs were urban, while 302 dogs were rural. Among the latter, 190 were
      shepherd dogs and 112 were cattle farm dogs. Sera were tested for the presence of
      antibodies against Neospora caninum using the Neospora agglutination test.
      Seroprevalence at 1/40, 1/80, 1/160 dilution titres was significantly higher in
      rural (36.4%, 19.5%, 9.9% respectively) than in urban dogs (20.2%, 10.6%, 4.8%
      respectively). Seroprevalence did not differ significantly in males and females.
      In shepherd dogs, prevalence increased according to dogs' age, thus suggesting a
      post-natal exposure by horizontal transmission. The observed higher
      seroprevalence in rural dogs suggests the importance of lifestyle and alimentary
      habits (i.e. aborted foetuses, placentas and small mammals) in the acquisition of
      N. caninum infection. Our results confirm that dogs are exposed to N. caninum and
      play an important role in the epidemiology of N. caninum.

PMID- 17456145
TI  - Application of different methods for the diagnosis of experimental
      paratuberculosis in goats.
AB  - The diagnosis of subclinical paratuberculosis is still considered a major problem
      worldwide. As part of investigating diagnostic strategies for the
      paratuberculosis infection, sequential results of various diagnostic methods in a
      progressive experimental infection in goats were evaluated. Twenty-three goat
      kids were divided into three groups: the infected, contact and control,
      comprising 10, five and eight goats respectively. Animals of the infected group
      were orally inoculated on seven occasions with 5 ml of inoculum containing 2 x
      10(9)Mycobacterium avium ssp. paratuberculosis per ml. Lymphoycte proliferation
      test using johnin PPD detected paratuberculosis infection from 60 days post
      infection (DPI) onwards. The johnin PPD was found to be a better antigen for the
      proliferative assays as compared with the sonicated antigen. The faecal smear
      examination with acid-fast staining detected more goats as positive than
      bacterial culture and polymerase chain reaction (PCR). Lipoarabinomannan enzyme
      linked immunosorbent assay (ELISA) started detecting infected goats from 150 DPI
      onwards followed by indirect ELISA and agar gel immunodiffusion from 180 DPI
      onwards. Histological examination was confirmatory and detected five infected
      goats as positive.

PMID- 17456146
TI  - Comparison of duplex PCR and microscopic techniques for the identification of
      Babesia bigemina and Babesia bovis in engorged female ticks of Boophilus
      microplus.
AB  - A single-step duplex polymerase chain reaction (PCR) technique and traditional
      microscopic examination of haemolymph smears were used to detect Babesia bigemina
      and/or Babesia bovis infection in engorged female ticks of Boophilus microplus
      recovered from calves raised in an endemic area of the State of Minas Gerais,
      Brazil. In the PCR amplification of tick-derived DNA, pairs of oligonucleotide
      primers specific for a 278-bp sequence from B. bigemina and for a 350-bp sequence
      from B. bovis were used conjointly. The microscopic examination of haemolymph
      revealed that 16.7% of the engorged ticks were infected with Babesia spp.,
      although no significant differences (rho > 0.05) were found in the infection rate
      of ticks collected from calves of different age groups. PCR analysis showed that
      77.8% of the engorged ticks whose haemolymph contained sporokinetes were infected
      with B. bigemina, 7.8% with B. bovis and 14.4% with both protozoan species.
      However, the PCR assay further revealed that, amongst the engorged female ticks
      whose haemolymph was apparently negative for the presence of sporokinetes, 15.6%
      were infected with B. bigemina, 2.2% with B. bovis and 10.0% with both species.
      The duplex PCR method is thus more efficient and sensitive than the microscopic
      assay and also permits facile identification of the protozoa species present in
      engorged female ticks.

PMID- 17456147
TI  - Immune response to and faecal shedding of Mycobacterium avium ssp.
      paratuberculosis in young dairy calves, and the association between test results
      in the calves and the infection status of their dams.
AB  - The objectives of this study were to: (i) evaluate the results of an intradermal
      skin test, a modified IFN-gamma test, and a commercial ELISA in commercially
      raised dairy calves at 2, 4, 6 and 8 months of age relative to faecal shedding of
      Mycobacterium avium ssp. paratuberculosis (MAP); (ii) determine the proportion of
      8-month-old calves shedding MAP in faeces as detected by culture and One Tube
      Nested Polymerase Chain Reaction (OTSN-PCR) and (iii) explore the association
      between results of tests described above in the calves and the Paratuberculosis
      (PTB) status of their dams as determined by faecal culture and/or serology. The
      study calves belonged to two dairy herds with different risk of exposure to MAP
      (high and low) and were enrolled based on their dam's ELISA results prior to
      calving. Approximately 3% of the calves were shedding MAP in faeces at 8 months
      of age. No agreement was observed among the evaluated immunity-based tests or
      between the immunity-based tests and the detection of MAP in faeces. Although no
      association was observed between the infection status of the dam and the results
      from the IFN-gamma and skin tests on the calves, there is an indication that
      calves born from dams that were faecal shedders might be at a higher risk of
      testing positive to the IFN-gamma test at 8 months of age. The disagreement among
      all tests evaluated in this calf cohort suggests that the detection of MAP
      infection in young stock requires the use of combined multiple tests. The early
      detection of PTB in calves is a challenge that requires further exploration of
      new methods to confirm infection status. These new testing methods should be both
      affordable and compatible with regular husbandry practices.

PMID- 17456148
TI  - Antibacterial activity of bovine lactoferrin hydrolysate against mastitis
      pathogens and its effect on superoxide production of bovine neutrophils.
AB  - Antibacterial activity of bovine lactoferrin hydrolysates (LFH) on microorganisms
      isolated from bovine mastitis, and superoxide (O(2)(-)) production of bovine
      neutrophils were evaluated. Antibacterial effects of LFH were measured in vitro
      against Staphylococcus aureus, coagulase-negative staphylococci, Streptococci,
      Enterococci, Escherichia coli, Klebsiella pneumoniae, yeast-like fungi and
      Prototheca zopfii isolated from clinical cases of bovine mastitis. To compare
      susceptibilities against LFH, minimal inhibitory concentration (MIC) values were
      determined by a micro-plate assay method. Most organisms were sensitive to LFH.
      Prototheca zopfii was highly sensitive to LFH; the growth of the microorganism
      was inhibited completely even at 1 mug/ml. Staphylococcus aureus and Escherichia
      coli were resistant to LFH. The production of O(2)(-) by bovine neutrophils was
      used to evaluate the effect of LFH administration on functional activity.
      Increase in O(2)(-) production by bovine neutrophils occurred upon addition of
      LFH to neutrophils. These results demonstrate that LFH possesses antibacterial
      activity against pathogens that cause mastitis and activates neutrophil
      superoxide production.

PMID- 17456149
TI  - Comparison of a commercial ELISA with the modified agglutination test for the
      detection of Toxoplasma gondii infection in naturally exposed sheep.
AB  - Surprisingly few commercial ELISAs are available for the detection of Toxoplasma
      gondii infection in animals, and none for use in sheep have been evaluated. We
      thus compared the Bommeli Diagnostics ELISA Toxotest for the detection of T.
      gondii antibodies in ruminants with the reference modified agglutination test
      (MAT) in a series of 180 sheep sera. ELISA results were analysed at two cut-off
      levels (30%, comprising both weakly positive and positive results, and 100%,
      comprising only positive results), and compared with MAT at three cut-off levels
      (titre of 1 : 25, 1 : 50 and 1 : 100). The results showed a moderate agreement of
      ELISA at both cut-offs (kappa = 0.46 and 0.51) with MAT at a cut-off titre of 1 :
      100. However, the specificity and positive predictive value were above 95% only
      at an ELISA cut-off of 100%, indicating its potential as a diagnostic test,
      particularly in areas with a high prevalence of infection. On the other hand,
      lower sensitivity and negative predictive value limit its value as a screening
      test. Thus, the ELISA Toxotest may be used for quick diagnosis of T. gondii
      infection in sheep in the field, i.e. for the differential diagnosis of ovine
      abortion storms.

PMID- 17456151
TI  - Recombinant-activated coagulation factor VIIa (NovoSeven): current development.
AB  - Recombinant activated coagulation factor VII (rFVIIa) was developed initially for
      treatment of patients with hemophilia and neutralizing antibodies ("inhibitors")
      to coagulation factors VIII or IX. Owing to the unique and selective mechanism of
      action of rFVIIa and encouraged by clinical experience with other circumstances
      of inadequate hemostasis, a broad development program has been pursued to test
      potential efficacy and evaluate safety of this biologic for indications other
      than hemophilia. This review summarizes the current development of rFVIIa,
      focusing on results of prospective, randomized clinical trials.

PMID- 17456152
TI  - Infectious complications following unrelated cord blood transplantation.
AB  - INTRODUCTION: Infections following cord blood transplantation are just beginning
      to be defined in the literature. This review will outline infections at death,
      the epidemiology of individual infections, and the impact of stem cell source.
      METHODS: A review of studies published since 2000. RESULTS: Based on registry
      data, most studies demonstrate an approximate rate of infection at death of 30
      40% among cord blood recipients. Bacterial infections often occur prior to
      engraftment and increase among patients with graft failure. In addition, there is
      delayed recovery of the immune response among patients with graft-versus-host
      disease that leads to viral infections at later time points. The risk of serious
      infection among children receiving umbilical cord blood (UCB) grafts is
      comparable to that of children receiving unmanipulated marrow and is lower than
      that of recipients of a T-cell-depleted stem cell source. Among adult patients,
      despite an overall higher incidence of serious infections after UCB
      transplantation as compared with unrelated donor grafts, non-relapse mortality
      and overall survival were not significantly different between haematopoietic stem
      cell sources. CONCLUSIONS: Further studies are needed to confirm these
      observations and determine whether the risk of infection for cord blood
      recipients is comparable to that of recipients of unmanipulated marrow.

PMID- 17456153
TI  - First case of hepatitis C virus transmission by a red blood cell concentrate
      after introduction of nucleic acid amplification technique screening in Germany:
      a comparative study with various assays.
AB  - BACKGROUND AND OBJECTIVES: Pooled nucleic acid amplification techniques (NAT) and
      donor screening for anti-hepatitis C virus (HCV) have reduced the diagnostic
      window period of HCV infection in the blood donor population from about 12 to 1
      or 2 weeks. During that time, HCV RNA is hardly detectable by pooled or
      individual donation NAT. Here we describe a case of transfusion-acquired HCV
      infection from an extremely low-titre donation. After a repeat donor tested
      positive for HCV, a look-back procedure was initiated. A recipient of a red cell
      concentrate from the previous donation was identified and found to be infected
      with HCV as well. We compared several commercial NAT systems for their ability to
      detect the viraemic plasma. MATERIALS AND METHODS: Molecular analyses of HCV in
      donor and recipient samples were performed. The HCV-transmitting plasma was
      tested using different commercially available qualitative and quantitative NAT
      assays. RESULTS: HCV transmission was verified by molecular analyses and was
      assigned to genotype 2b. NAT with various commercial HCV assays detected the
      infection erratically in individual donations. However, the detection rate was
      not directly related to the claimed sensitivity of some HCV NATs. CONCLUSIONS:
      HCV transmission can be caused by donations that escape NAT detection even when
      tested in an individual donation. Comparison of different assays led to results
      that did not necessarily reflect the expected sensitivities. The need for
      standard materials representing further HCV genotypes is discussed.

PMID- 17456154
TI  - Reference materials for the evaluation of pre-mortem variant Creutzfeldt-Jakob
      disease diagnostic assays.
AB  - BACKGROUND AND OBJECTIVES: A standard panel of materials is needed for the
      evaluation of assays being developed for the diagnosis of variant Creutzfeldt
      Jakob disease. MATERIALS AND METHODS: Tissues from human and animals incubating
      transmissible spongiform encephalopathy disease have been prepared, aliquoted and
      where possible characterized by in vitro methods. RESULTS: A standardized
      preparation of materials has been generated. CONCLUSIONS: Large-scale
      preparations of tissues and blood fractions can be used to directly compare the
      sensitivities of assays using different formats.

PMID- 17456155
TI  - Metabolic energy reduction by glucose deprivation and low gas exchange preserves
      platelet function after 48 h storage at 4 degrees C.
AB  - INTRODUCTION: We showed earlier that metabolically suppressed platelets (MSP)
      prepared by incubation in glucose-free, antimycin A medium at 37 degrees C better
      sustained storage at 4 degrees C than untreated controls at 22 degrees C.
      However, the use of the mitochondrial inhibitor antimycin A is incompatible with
      platelet transfusion. OBJECTIVES: The aim of this study was to investigate how
      energy-reduced (ER) platelets could be prepared in the absence of antimycin A.
      STUDY DESIGN AND METHODS: Platelets in gas-impermeable bags in glucose-free
      medium were kept at 22 degrees C for 4 h to reduce energy stores and thereafter
      stored at 4 degrees C (ER22-4). Controls were energy-reduced platelets without
      prior incubation at 22 degrees C (ER4), and MSPs in test tubes and untreated
      platelets in gas-permeable bags with glucose and stored at 22 degrees C (C22) and
      4 degrees C (C4). RESULTS: After 48 h storage, ER22-4 were superior to C22 with
      respect to pH preservation (6 x 4 +/- 0 x 4 vs. 5 x 0 +/- 0 x 4, n= 4), platelet
      count (800 +/- 225 vs. 650 +/- 150 x 10(9)), thrombin receptor-activating peptide
      induced aggregation (50 +/- 15 vs. 10 +/- 5%) and glycoprotein (GP)Ib alpha
      expression (60 +/- 15% vs. 28 +/- 15). GPIb alpha expression was higher in ER22-4
      than in ER4, indicating that energy suppression preserved GPIb alpha during cold
      storage. CONCLUSION: Metabolic suppression without the use of antimycin A could
      be mimicked by storage of platelets in glucose-free medium in gas-impermeable
      bags. Energy suppression preserved GPIb alpha expression during storage at 4
      degrees C.

PMID- 17456156
TI  - Quality and safety of fresh-frozen plasma inactivated and leucoreduced with the
      Theraflex methylene blue system including the Blueflex filter: 5 years'
      experience.
AB  - BACKGROUND AND OBJECTIVES: The objective of this paper is to present 5 years'
      experience of pathogen inactivation of fresh-frozen plasma with the methylene
      blue system in a blood centre in Athens. MATERIALS AND METHODS: Eight thousand
      and five hundred units treated by methylene blue and 54 435 untreated were issued
      for transfusion in four hospitals during the period 2000-2005. Eighty-eight units
      were evaluated for changes in coagulation factor activity and cytokine
      concentrations following treatment. RESULTS: Coagulation factor losses were in
      the accepted range. Adverse reactions were 1 : 8500 with treated and 1 : 2177
      with untreated units. The five serious reactions were all in untreated units. No
      seroconversions for infectious diseases were reported. CONCLUSIONS: Methylene
      blue-treated fresh-frozen plasma is safer than the untreated product even in
      patients who require large quantities of plasma transfusion.

PMID- 17456157
TI  - A solvent/detergent-treated and 15-nm filtered factor VIII: a new safety standard
      for plasma-derived coagulation factor concentrates.
AB  - BACKGROUND: Since the early 1990 s the Committee for Proprietary Medicinal
      Products has set the mandatory requirement that all manufacturing processes for
      blood products include two virus removal/inactivation steps that are
      complementary in their action. OBJECTIVES: The objective was to develop a
      manufacturing process for factor VIII (FVIII) including two complementary steps
      of viral inactivation/elimination. METHODS: A 35-15 nm nanofiltration step was
      added to a former FVIII manufacturing process that included solvent/detergent
      (S/D) treatment to generate a new FVIII concentrate called Factane. The impact of
      nanofiltration on the structural and functional characteristics of FVIII, as well
      as virus/transmissible spongiform encephalopathy reduction factors were assessed.
      RESULTS: Using an innovative approach, FVIII was successfully nanofiltered at 35
      15 nm, while the biological properties of the active substance were unmodified.
      FVIII coagulant and antigen content for Factane and previous S/D-treated FVIII
      (FVIII-LFB, commercialized as Facteur VIII-LFB) were comparable. The FVIII one
      stage chromogenic and coagulant/antigen ratios confirmed that nanofiltered FVIII
      was not activated. After nanofiltration, the copurified von Willebrand factor
      (vWF) was reduced but vWF/FVIII binding properties were unaffected. Phospholipid
      binding and thrombin proteolysis studies displayed no differences between Factane
      and FVIII-LFB. The rate of factor Xa generation was slightly lower for Factane
      when compared to FVIII-LFB. Viral validation studies with different viruses
      showed no detectable virus in the filtrate. CONCLUSIONS: Nanofiltration of FVIII
      at 15 nm is feasible despite the large molecular weight of FVIII and vWF.
      Nanofiltration has been proven to be highly effective at removing infectious
      agents while preserving the structural and functional integrity of FVIII.

PMID- 17456159
TI  - Blood donor derived dendritic cells and cytotoxic T cells for specific fusion
      gene adoptive immunotherapy.
AB  - BACKGROUND AND OBJECTIVES: Therapeutic immunological reagents tailored to
      individual patients have been shown to be a viable treatment strategy for some
      forms of leukaemia. This work investigates the possibility of using blood
      donations as a source of leukaemia-specific immune therapeutics. MATERIALS AND
      METHODS: The acute promyelocytic cell line NB4 carrying the PML-RAR alpha fusion
      was used as a target for cytotoxic T lymphocytes (CTL) stimulated to recognize
      the fusion. Stimulation of CTL was by production of dendritic cells pulsed with
      plasmid vectors containing polymerase chain reaction (PCR)-generated sequences of
      PML-RAR alpha derived from NB4 cells. PCR primer design included a Kozak
      consensus sequence to allow correct translation of the nucleic acid into protein.
      Identification of specific cytotoxicity was by both Granzyme B ELISPOT and by
      (51)Cr-release assays. RESULTS: Specific CTL activity targeting NB4 cells can be
      generated from donor-derived peripheral blood mononuclear cells. However,
      individual donors appear to respond differently to the length of stimulatory
      sequence encoded in the vector. Use of an internal methionine in the PML gene,
      which also satisfies the Kozak rules, allows translation in vitro and, thus,
      might provide a suitable start site for stimulation using acute promyelocytic
      leukaemia-specific sequence. CONCLUSION: The work presented here suggests that
      blood donor derived dendritic cells can be used to stimulate leukaemia-specific
      CTL from the same donation ex vivo. This would enable the generation of patient
      specific therapeutics from major histocompatibility (MHC)-matched allogeneic
      donors. However, different MHC-matched donors might vary in their response
      depending on the length of the antigenic sequence.

PMID- 17456158
TI  - Second-generation nanofiltered plasma-derived mannan-binding lectin product:
      process and characteristics.
AB  - BACKGROUND AND OBJECTIVES: Mannan-binding lectin (MBL) is an important component
      of the innate immune defence; it binds to carbohydrate structures on pathogenic
      micro-organisms resulting in complement activation and opsonization. Individuals
      with low MBL levels are at risk of recurrent and severe infections. Substitution
      therapy with plasma-derived MBL is a promising treatment of diseases associated
      with MBL deficiency. A first-generation MBL product has been shown to be safe and
      well tolerated, and patients have benefited from MBL treatment. Following is a
      description of the development of a nanofiltered second-generation MBL product
      from Cohn fraction III, with the use of a new affinity matrix for MBL
      purification and the characteristics of this improved product. MATERIALS AND
      METHODS: Carbohydrate-based gels were comparatively screened as affinity
      matrices. MBL was extracted from fraction III, and affinity purified on a
      Superdex 200 pg column. The eluted material underwent two virus reduction steps:
      filtration through Planova 20N and solvent/detergent treatment. It was further
      purified by anion-exchange and gel-filtration chromatography. The affinity eluate
      and the final MBL fraction were characterized by protein chemical, immunological,
      and functional assays. RESULTS: In production scale, Superdex 200 pg was found to
      be superior to other carbohydrate-based matrices, and MBL was affinity purified
      from fraction III with a yield of 70%. The viral safety was increased by
      performing a nanofiltration of the affinity eluate through Planova 20N with a
      minimal loss of MBL. The purity of the final MBL fraction was 53% excluding the
      MBL-associated serine proteases (MASP). The product consisted of high-oligomeric
      MBL, with two dominating forms, and with MASP-1, -2, -3 and 19 kDa MBL-associated
      protein (MAp19). Only a few protein impurities were present, the major being
      alpha2-macroglobulin. MBL formed complexes with alpha2-macroglobulin bridged by
      MASP-1 covalently attached to the latter. The functional activity, assessed by
      mannan-binding activity and opsonic function, was intact, whereas half of the C4
      activating capacity was lost during the production process. CONCLUSION: A second
      generation MBL process was developed with an average yield of 50%. It was
      possible to nanofilter the MBL-MASP complexes through Planova 20N with only a
      minor loss resulting in an increased safety profile of this MBL product.

PMID- 17456160
TI  - What would encourage blood donation in Ireland?
AB  - BACKGROUND: Recent changes have resulted in the loss of 4% of the donor panel in
      the Republic of Ireland and 3% in Northern Ireland. In order to increase the
      number of donors in these two regions, it is important that transfusion service
      providers explore and understand the reasons, which prevent individuals from
      donating. The aim of this study was to explore these issues particularly in non
      donors and those who had lapsed. METHODS: This 7-month all-Ireland study was
      conducted by computer-assisted telephone interview. Data collected included
      sociodemographic history, donation status, as well as barriers/deterrents to
      donation. RESULTS: There were 4166 completed questionnaires (44% donors; 56% non
      donors). Of the donors, 13% had donated blood within the last 2 years. Current
      donors cited 'awareness of patients needs' (88%), 'trust in the blood transfusion
      service' (70%), and 'an advertising campaign' (70%) as reasons encouraging them
      to donate blood. Lapsed donors and non-donors cited 'more frequent mobile
      clinics/sessions' (30% lapsed donors; 53% non-donors), 'if I was asked' (28%
      lapsed donors; 53% non-donors), and 'more flexible opening hours' (23% lapsed
      donors; 44% non-donors) as reasons that would encourage them to donate. The main
      reasons cited by non-donors for never having donated included 'medical reasons'
      (41% Republic of Ireland; 43% Northern Ireland), 'lack of information' (20%
      Republic of Ireland; 22% Northern Ireland), 'fear of needles' (15% Republic of
      Ireland; 17% Northern Ireland), and 'time constraints' (12% Republic of Ireland;
      13% Northern Ireland). Among the non-donor group, 10% (Republic of Ireland) and
      6% (Northern Ireland) claimed that they are not permitted to donate. CONCLUSION:
      Replacing regular donors is a major challenge for the transfusion service
      providers. This study shows that by facilitating the general public by
      introducing more mobile clinics/sessions, more flexible opening hours and having
      a better level of knowledge in the community about blood donation may encourage
      lapsed donors and new donors to become regular donors.

PMID- 17456161
TI  - Effect of changing the age criteria for blood donors.
AB  - BACKGROUND AND OBJECTIVES: The upper age limit for allogeneic blood donation
      varies among countries and blood operators. We assessed the impact of the removal
      of the upper age limit for donation in Canada from December 2004 to January 2006.
      MATERIALS AND METHODS: Starting in December 2004, regular donors were permitted
      to continue whole blood or apheresis donation past their 71st birthday, provided
      an annual external medical assessment was performed by their family physician.
      Regular donors aged from 70 to 74 were sent a letter about the change in
      criteria, and encouraged to continue donations. Rates of donor adverse reactions
      and deferrals were calculated for these donors and donors in other age groups.
      RESULTS: In the 13-month period following implementation of the new criteria, 961
      (54%) of regular donors who had received a letter initiated a medical inquiry,
      and 862 inquiries were completed and returned to Canadian Blood Services. In 98%
      of cases, the donors' family physician approved ongoing donation. Of the 659
      donors who presented to donate, 93% successfully donated. There was only one
      moderate/severe donor reaction out of 3137 donor attendances for donors aged 71
      and older. This rate was not statistically different from the rate in the overall
      donor population. No donors were deferred for high-risk activities or had
      positive infectious disease test results. CONCLUSION: Regular blood donors may
      safely continue to donate past their 71st birthday. Extra steps in the donation
      process, such as an external medical inquiry, may not be necessary.

PMID- 17456162
TI  - Real-time multiplex allele-specific polymerase chain reaction for genotyping of
      the Duffy antigen, the Plasmodium vivax invasion receptor.
AB  - BACKGROUND AND OBJECTIVES: Duffy blood group is of major interest in clinical
      medicine as it is not only involved in blood-transfusion risks and occasionally
      in neonatal haemolytic disease, but it is also the receptor for the human malaria
      parasite Plasmodium vivax in the erythrocyte invasion. The aim of this study was
      to develop a rapid and inexpensive approach for high-throughput Duffy genotyping.
      MATERIALS AND METHODS: This paper reported the development of a Duffy genotyping
      assay based on multiplex real-time polymerase chain reaction (PCR) using SYBR
      Green I fluorescent dye. RESULTS: By using this approach for Duffy genotyping we
      obtained the same results as that for the conventional allele-specific PCR,
      however, in a high-throughput assay. The Duffy genotyping of field samples
      demonstrated that P. vivax-infected individuals showed a significantly higher
      prevalence of two functional alleles than Plasmodium falciparum-infected and non
      infected individuals. This finding corroborates the hypothesis that the presence
      of two functional alleles increases the risk of P. vivax infection. CONCLUSION:
      This methodology may be suitable for epidemiological studies, particularly for
      exploring the relationship between Duffy alleles and malaria susceptibility, and
      also for identification of transfusional incompatibility in blood banks.

PMID- 17456163
TI  - Massive blood transfusion and mortality in polytrauma patients.

PMID- 17456164
TI  - Mistransfusion in the emergency room.

PMID- 17456166
TI  - The darker side of groups.
AB  - This paper examines the role of group interaction in the workplace and the impact
      of anxiety on group cohesion. It takes a psychoanalytical perspective and
      highlights how early learning within a familial setting influences later
      attitudes and behaviour at work. In particular the article focuses on the signs
      of negative group anxiety and how the manager can recognise anti-group culture.
      By recognising the negative signs the leader can also come to understand how the
      anti-group develops and thereby prevent the resulting disruptive behaviour. In
      some instances the perception of anti-group feelings and behaviour can also be
      altered so that the team leader can reach a positive outcome for the group
      dynamic and resultant team cohesion and collaboration.

PMID- 17456167
TI  - Interdisciplinary teamwork: is the influence of emotional intelligence fully
      appreciated?
AB  - AIM: The purpose of this study is to discuss how emotional intelligence affects
      interdisciplinary team effectiveness. Some findings from a larger study on
      interdisciplinary teamworking are discussed. BACKGROUND: Teams are often
      evaluated for complementary skill mix and expertise that are integrated for
      specialist service delivery. Interactional skills and emotional intelligence also
      affect team behaviour and performance. An effective team needs both emotional
      intelligence and expertise, including technical, clinical, social and
      interactional skills, so that teamwork becomes greater or lesser than the whole,
      depending on how well individuals work together. KEY ISSUES: Team diversity,
      individuality and personality differences, and interprofessional safety are
      analysed to raise awareness for nurse managers of the complexity of
      interdisciplinary working relationships. CONCLUSION: If nursing input into
      interdisciplinary work is to be maximized, nurse managers might consider the role
      of emotional intelligence in influencing team effectiveness, the quality of
      client care, staff retention and job satisfaction.

PMID- 17456168
TI  - Factors influencing nurses' decisions to raise concerns about care quality.
AB  - AIM: To explore factors that influence nurses' decisions to raise concerns about
      standards of practice. BACKGROUND: Health care practitioners have a key role in
      monitoring care quality. Nurses are required by their professional body to raise
      concerns about standards; however, under-reporting is the norm. METHOD: Grounded
      theory was used to collect and analyse data from semi-structured interviews with
      142 practising nurses, theoretically sampled from three Acute NHS Trusts in
      England. FINDINGS: Fear of repercussions, retribution, labelling and blame for
      raising concerns, about which they predicted nothing would be done, were
      identified as disincentives to raising concerns. Reporting was perceived as a
      high-risk:low-benefit action. Nurses lacked confidence in reporting systems.
      CONCLUSIONS: Disincentives to reporting need to be addressed if an open culture,
      which promotes quality, safety and learning, is to be developed. Findings give
      cause for concern and indicate a need to review organizational and professional
      guidelines, and organizational reporting systems.

PMID- 17456169
TI  - Self-reported perceptions of Registered Nurses working in Australian hospitals.
AB  - AIM: The purpose of this study is to develop an understanding of work
      environments by analysing the perceptions of a sample of Registered Nurses (RNs).
      BACKGROUND: Within the context of high staff turnover and a shortage of nurses in
      the health workforce, it is important that we understand how nurses perceive
      their work context and view the organisational factors that influence their
      attitudes towards their workplace. METHODS: Data was collected using a 160
      question survey instrument seeking information from RNs in relation to work and
      perceptions of the work environment and the organisation. The sample was
      recruited from a convenience sample of three acute hospitals in Queensland,
      Australia. A response rate of 41% was achieved (n=343). RESULTS: Respondents
      across the three survey sites identified a number of variables that had
      particular impact on their working lives. Team interaction, providing good
      patient care, communication, and abuse towards RNs elicited strong responses by
      the study respondents. As well, organisational direction, strategy and management
      returned strong negative responses. In responding to the questions related to
      personal and organisational morale it was clear that respondents saw them as two
      distinct concepts. CONCLUSIONS: The results of this study have implications for
      nurse managers in terms of understanding the nursing workforce as well as key
      organisational factors that have both positive and negative influences on the
      perceptions of nurses.

PMID- 17456170
TI  - Early nursing career experience for 1994-2000 graduates from the University of
      Nottingham.
AB  - AIM: This paper reports the views of nurses graduating from the University of
      Nottingham School of Nursing, UK, 1994-2000, Bachelor of Nursing (Hons) course,
      concerning career aspirations, progress and reflections on their qualification.
      BACKGROUND: Alongside academic knowledge and practical skills, this four-year
      Bachelor of Nursing course aimed to develop students' critical thinking and
      research skills. The degree's effect on nurses' career trajectories is unknown.
      METHODS: Self-completion questionnaires employing open and closed questions were
      sent to graduates 9 months after graduation and at intervals over the next 6
      years. RESULTS: Most respondents were confident and motivated in their nursing
      careers. Promotion, increased responsibility, further study, specialization and
      qualifications were career priorities. Recent qualifiers also focused on changing
      jobs, travel and working overseas. CONCLUSION: The graduates' experience has
      salience for nurse managers, especially when matching graduates against post
      outlines within the knowledge and skills framework, considering staff skill mix,
      and advising graduates about their development and assisting them to find
      satisfaction in their nursing careers.

PMID- 17456171
TI  - Change in career aspirations and job values from study time to working life.
AB  - AIM: The main aim of this paper is to uncover whether the actual career choices
      and job values of newly qualified nurses are in accordance with the predictions
      they made at the commencement of their nursing education. BACKGROUND: A cohort of
      Norwegian nurse students was followed from the beginning of their education in
      1998 through nursing school and 2,years after graduating. METHODS: Questionnaire
      data from 221 nursing students at three points in time: 1998, 2001 and 2003 were
      analysed with frequency distributions and paired samples t-tests. For 140
      respondents data from all three points were available. RESULTS: Initially motives
      like human contact, helping others, job security were important, and 92% had a
      wish for further education. Career preferences were often midwifery, public heath
      and nursing practice in high tech areas. Towards the end of the bachelor course
      (2001), there was more ambiguity in the helping motives. On one hand, the
      students wanted to be altruistic but on the other hand, they wanted gratitude in
      return when giving help to patients. Seventy five per cent of the students had
      plans for further education within a period of about 2 years after graduation.
      Midwifery, public health work and high tech practice were still preferred.
      Findings from 2003 indicated only 16% had started or finished further education 2
      years after graduation. When appraising future job challenges in 2001 and 2003,
      there is a decrease in emphasis on the values human contact and part-time work
      and an increase in emphasis on high salary and job security. CONCLUSIONS: During
      the student period, the bachelor programme was regarded as a basis for further
      education, but 2 years after graduation only 16% had realized further education.
      Preferences related to job values regarding a prospective job reveal a decrease
      in the importance of human contact and an increase in the importance of a high
      salary and job security from 2001 to 2003.

PMID- 17456172
TI  - Evaluation of Return to Practice: the views of nurse returnees from three NHS
      Hospital Trusts.
AB  - AIM: Exploration of the views and experiences of returnees on a Return to
      Practice programme based in three NHS Hospital Trusts. BACKGROUND: In the light
      of nursing shortages in Britain, there is an ongoing need to encourage nurses to
      re-enter the profession through Return to Practice programmes. In order to
      maximize returnees' participation in the nursing workforce; however, evaluation
      of the effectiveness of Return to Practice programmes is necessary. METHOD: 17
      returnees were recruited to the study completing self-report questionnaires at
      programme commencement and participating in focus group discussions on programme
      completion. FINDINGS: Three key issues emerged from the data: the varied personal
      circumstances and professional histories of returnees; the challenge of providing
      adequate support in practice that reflected returnees' individual needs and
      aspirations and the importance of flexible employment opportunities to meet
      returnees' expectations of an appropriate work life balance. CONCLUSIONS: It is
      important that any schemes to attract nurses back to the profession are targeted
      at their specific needs.

PMID- 17456173
TI  - Budgeting nursing workload for required minimum data set assessments.
AB  - AIM: The purpose of this study was to evaluate the reliability and validity of an
      instrument used to measure nursing workload of federally mandated assessments.
      Specifically, the instrument measures the nursing workload of the resident
      assessment instrument the mandated assessment tool used in nursing facilities.
      BACKGROUND: It is imperative that nursing managers and nurse executives in health
      care organizations have a process to budget Registered Nurse full-time
      equivalents required for federally mandated assessments. METHODS: The sample
      (N=48) included nursing facility minimum data set Coordinators. Reliability and
      validity scores of the nursing workload instrument are calculated using Pearson
      correlation coefficients (r). RESULTS: The nursing workload instrument
      demonstrated reliability and validity. Total nursing workload to complete the
      minimum data set for nursing facilities is summarized. CONCLUSION: The results
      provide support for a reliable and valid instrument to measure nursing workload
      for standardized minimum data set assessments.

PMID- 17456174
TI  - The costs of training a nurse practitioner in primary care: the importance of
      allowing for the cost of education and training when making decisions about
      changing the professional-mix.
AB  - What is already known on this topic * Cost containment through the most effective
      mix of staff achievable within available resources and organisational priorities
      is of increasing importance in most health systems. However, there is a dearth of
      information about the full economic implications of changing skill mix. * In the
      UK a major shift in the primary care workforce is likely in response to the
      rapidly developing role of nurse practitioners and policies aimed to encourage GP
      practices to transfer some of their responsibilities to other, less costly,
      professionals. * Previous research has developed an approach to incorporating the
      costs of qualifications, and thus the investment required to develop a skilled
      workforce, for a variety of health service professionals including GPs. What this
      study adds * This paper describes a methodology of costing nurse practitioners
      that incorporates the human capital cost implications of developing a skilled
      nurse practitioner workforce. With appropriate sources of data the method could
      be adapted for use internationally. * Including the full cost of qualifications
      results in nearly a 24 per cent increase in the unit cost of a Nurse
      Practitioner. * Allowing for all investment costs and adjusting for length of
      consultation, the cost of a GP consultation was nearly 60 per cent higher than
      that of a Nurse Practitioner.

PMID- 17456175
TI  - A theoretical argumentation on the consequences of moral stress.
AB  - BACKGROUND: Intensive care units are characterized by heavy workloads, increasing
      work complexity and ethical concerns related to life-and-death decisions. In the
      present study, it is assumed that there is a relationship between moral stress,
      support and competence for nurses in intensive care units. AIM: To analyse and
      describe the theoretical relationship between moral stress and support on the one
      hand and competence on the other, in the context of intensive care. METHOD: A
      form of qualitative secondary analysis based on the findings from three original
      studies. In the analytic process a theory on professional competence was used.
      FINDINGS: The findings suggest that imbalance due to moral stress between
      different competences hinders the development of collectively shared caring
      competence. CONCLUSIONS: Moral stress cannot be totally eliminated in the
      intensive care unit. But moral stress is not only a problem. It can also become a
      driving force to stimulate competence.

PMID- 17456178
TI  - Characterization of Streptococcus pneumoniae isolated from children with otitis
      media.
AB  - Streptococcus pneumoniae is the main causative agent of acute otitis media in
      children. Serotype-based vaccines have provided some protection against otitis
      media, but not as much as anticipated, demonstrating the need for alternative
      vaccine options. Pneumococcal otitis media isolates were obtained from children 5
      years old or younger from hospitals around Mississippi in the prevaccine era
      (1999-2000). These isolates were compared by capsular typing, pneumococcal
      surface protein A (PspA) family typing, antibiotic susceptibility, and DNA
      fingerprinting. Our study shows that there is great genetic variability among
      pneumococcal clinical isolates of otitis media, except with regard to PspA.
      Therefore, efforts focused on the development of a PspA-based pneumococcal
      vaccine would be well placed.

PMID- 17456179
TI  - Chloroquine is therapeutic in murine experimental model of
      paracoccidioidomycosis.
AB  - Chloroquine, due to its basic properties, has been shown to prevent the release
      of iron from holotransferrin, thereby interfering with normal iron metabolism in
      a variety of cell types. We have studied the effects of chloroquine on the
      evolution of experimental paracoccidioidomycosis by evaluating the viable fungal
      recovery from lung, liver and spleen from infected mice and H(2)O(2), NO
      production, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-10
      levels and transferrin receptor (TfR) expression from uninfected and infected
      peritoneal macrophages. Chloroquine caused a significant decrease in the viable
      fungal recovery from all organs tested, during all periods of evaluation.
      Peritoneal macrophages from chloroquine-treated infected mice showed higher
      H(2)O(2) production and TfR expression, and decreased levels of NO, endogenous
      and stimulated-TNF-alpha, IL-6 and IL-10 during the three evaluated periods.
      However, despite its suppressor effects on the macrophage function, the
      chloroquine therapeutic effect upon murine paracoccidioidomycosis was probably
      due to its effect on iron metabolism, blocking iron uptake by cells, and
      consequently restricting iron to fungus growth and survival.

PMID- 17456180
TI  - Distribution and characterization of integrons in Escherichia coli strains of
      animal and human origin.
AB  - One hundred and twenty clinical and commensal Escherichia coli strains isolated
      in Switzerland from humans and from companion and farm animals were analysed for
      the prevalence of integrons of classes 1, 2, and 3 and for the characterization
      of their gene cassettes. The relationships between integron carriage and host
      category, and between integron carriage and phylogenetic E. coli lineage were
      also analysed. Integrons were detected in 48 (40%) of the isolates and were thus
      widely disseminated in the human and animal E. coli strains considered. Moreover,
      the association between integron carriage and certain animal categories (farm
      animals) suggests that animals that are raised for economic purposes might be
      exposed to a major antibiotic pressure. Finally, our data confirm that E. coli
      commensal strains represent a significant source of antibiotic-resistant
      determinants.

PMID- 17456181
TI  - Detection of constitutive molecules on Histoplasma capsulatum yeasts through
      single chain variable antibody fragments displayed in M13 phages.
AB  - A nonimmune library, containing single chain variable fragments (scFv) of
      immunoglobulin human genes displayed on the surface of M13 filamentous phages,
      was used to recognize molecules exposed on Histoplasma capsulatum yeasts'
      surface, during their growth in synthetic medium. The scFv clones were checked in
      their consistency by Dot-ELISA using HRP/anti-M13 conjugate, and they were tested
      to recognize molecules on H. Capsulatum yeasts' surface by ELISA in plates. Three
      out of 80 scFv cones (C2, C6, and C52) reacted consistently with H. capsulatum
      molecules, and they recognized molecules from both H. capsulatum morphologic
      phases. However, C6 and C52 clones reacted better with molecules on the surface
      of whole yeasts, with molecules from the yeasts' cell-wall extract, and with
      molecules released to the supernatant of the yeast culture. Mycelial supernatants
      from other fungi, as well as from a Mycobacterium filtrate, were not recognized
      by scFv phage monoclones. Monoclones C2, C6, and C52 recognized yeast molecules
      irrespective of the H. capsulatum strains used; the C6 clone revealed a specific
      immunohistochemistry reaction when tested against homologous and heterologous
      fungal infected tissues. The scFv clones isolated will be a useful toll to define
      the role of their target molecules in the host-parasite relationship of
      histoplasmosis.

PMID- 17456182
TI  - The O2-responsive repressor PpsR2 but not PpsR1 transduces a light signal sensed
      by the BphP1 phytochrome in Rhodopseudomonas palustris CGA009.
AB  - Regulatory properties of bacteriophytochrome BphP1 were evaluated with respect to
      the photosynthesis gene transcription repressors PpsR1 and PpsR2 of
      Rhodopseudomonas palustris strain CGA009 in gene complementation, replacement and
      deletion experiments. The results indicate that 750 nm wavelength light activates
      BphP1 to antagonize repression of photosynthesis gene expression by PpsR2, but
      not PpsR1. It is suggested that an equilibrium exists between BphP1-active and 
      inactive conformations, with 750 nm light shifting the equilibrium to an active
      conformation, although a phenotypically detectable component of BphP1 is in the
      active conformation in the absence of illumination.

PMID- 17456183
TI  - Inhibition of infection of the rice blast fungus by halisulfate 1, an isocitrate
      lyase inhibitor.
AB  - Halisulfate 1, a sesterterpene sulfate and an isocitrate lyase (ICL) inhibitor
      that is isolated from tropical sponge Hippospongia spp., reduces both
      appressorium formation and infection of rice plants by the fungus Magnaporthe
      grisea. Rice plants infected with wild-type M. grisea Guy 11 exhibited
      significantly lower disease severity after halisulfate 1 treatment than without,
      and the treatment effect was comparable to the behavior of the Delta icl knockout
      mutant I-10. The protection observed upon applying halisulfate 1 to rice plants
      suggests that the ICL inhibitor may be a promising candidate for crop protection,
      particularly to protect rice plants against M. grisea.

PMID- 17456184
TI  - Antifungal compounds from cultures of dairy propionibacteria type strains.
AB  - Antifungal compounds from cultures of five type strains of dairy
      propionibacteria, as well as from the cultivation medium, were studied. Cell-free
      supernatants and medium were fractionated by C(18) solid phase extraction. The
      aqueous 95% acetonitrile fractions were analyzed by GC-MS or subjected to
      reversed-phase HPLC, to identify, quantify or isolate antifungal substances. The
      resulting HPLC fractions were screened for antifungal activity against the mold
      Aspergillus fumigatus and the yeast Rhodotorula mucilaginosa. Active fractions
      were further separated by HPLC and the structures of the compounds were
      determined by spectroscopic and chromatographic methods. All five strains
      produced 3-phenyllactic acid, at concentrations ranging from 1.0 microg mL(-1)
      (Propionibacterium freudenreichii ssp. shermanii) to 15.1 microg mL(-1)
      (Propionibacterium thoenii), and at L/D -ratios ranging from 2 : 3
      (Propionibacterium acidipropionici) to 9 : 1 (Propionibacterium freudenreichii).
      A number of active compounds found in cultures of propionibacteria were also
      present in noninoculated growth medium: two antifungal diketopiperazines, cyclo(L
      Phe-L-Pro) and cyclo(L-Ile-L-Pro), and seven antifungal linear peptides. Three of
      the linear peptides corresponded to sequences found in the medium component
      casein, suggesting their origin from this component, whereas the
      diketopiperazines were suggested to be formed from medium peptides by heat
      treatment.

PMID- 17456185
TI  - Functional analysis of a lipid galactosyltransferase synthesizing the major
      envelope lipid in the Lyme disease spirochete Borrelia burgdorferi.
AB  - One of the major lipids in the membranes of Borrelia burgdorferi is
      monogalactosyl diacylglycerol (MGalDAG), a glycolipid recently shown to carry
      antigenic potency. Herein, it is shown that the gene mgs (TIGR designation
      bb0454) of B. burgdorferi encodes for the protein bbMGS that, when expressed in
      Escherichia coli, catalyzes the glycosylation of 1,2-diacylglycerol with
      specificity for the donor substrate UDP-Gal yielding MGalDAG. Related lipid
      enzymes were found in many Gram-positive bacteria. The presence of this
      galactosyltransferase activity and synthesis of a cholesteryl galactoside by
      another enzyme were verified in B. burgdorferi cell extract. Besides MGalDAG,
      phosphatidylcholine, phosphatidylglycerol, and cholesterol were also found as
      major lipids in the cell envelope. The high isoelectric point of bbMGS and
      clustered basic residues in its amino acid sequence suggest that the enzyme
      interacts with acidic lipids in the plasma membrane, in agreement with strong
      enzymatic activation of bbMGS by phosphatidylglycerol. The membrane packing and
      immunological properties of MGalDAG are likely to be of great importance in vivo.

PMID- 17456186
TI  - Diverse homologues of the archaeal repressor NrpR function similarly in nitrogen
      regulation.
AB  - NrpR is a transcriptional repressor of nitrogen assimilation genes that was
      recently discovered and characterized in the methanogenic archaeon Methanococcus
      maripaludis. NrpR homologues are widely distributed in Euryarchaeota and present
      in a few bacterial species. They exist in three different domain configurations:
      a single ORF encoding one NrpR domain following an N-terminal helix-turn-helix
      (HTH); a single ORF encoding two NrpR domains fused in tandem following an N
      terminal HTH; and two separate ORFs, one with a single domain following an N
      terminal HTH and one with a single domain without a HTH. Phylogenetic analysis
      indicated that the NrpR family forms five distinct groups: the single domain HTH
      type, the two domains of the double domain HTH type and the two separately
      encoded domains. To determine the function of diverse NrpR homologues,
      representative genes in were expressed an Methanococcus maripaludis nrpR deletion
      mutant. Homologues from species that possess a single gene restored regulated
      repression, regardless of domain structure. In the case of Methanosarcina
      acetivorans that contains two genes, both were required. The results show that
      distantly related NrpR homologues that are present in widely dispersed phyla
      regulate the expression of nitrogen assimilation genes in a similar fashion.

PMID- 17456187
TI  - Cold-active acetogenic bacteria from surficial sediments of perennially ice
      covered Lake Fryxell, Antarctica.
AB  - Cold-active acetogenic bacteria in the permanently cold sediments of Lake
      Fryxell, Antarctica were investigated using culture-based methods. Two
      psychrophilic, acetogenic strains were isolated and found to be physiologically
      and phylogenetically related to Acetobacterium bakii and Acetobacterium tundrae.
      However, the Antarctic isolates showed a lower growth temperature range than
      other species of Acetobacterium, with growth occurring from -2.5 to 25 degrees C
      and optimally at 19-21 degrees C. Cultures incubated at +5 and +1 degrees C grew
      with generation times of 7 and 9 days, respectively. The rapid growth of these
      strains at low temperatures suggests that acetogenesis may be an important
      anaerobic process in the sediments of Lake Fryxell.

PMID- 17456188
TI  - Mutagenesis of the carboxy terminal protease CtpA decreases desiccation tolerance
      in Rhizobium leguminosarum.
AB  - To better understand the role of proteases in Rhizobium leguminosarum biovar
      viciae, a gene with homology to the carboxy-terminal protease (CtpA), which
      belongs to a novel group of serine proteases, was studied. The ctpA gene was
      cloned and mutated using allelic exchange and a gusA reporter gene was used to
      study ctpA expression. Mutational analysis shows that ctpA is critical for the
      viability of R. leguminosarum when cells are grown on complex semi-solid media
      but is dispensable when cells are grown in complex liquid media and that this is
      likely due to an increase in susceptibility to desiccation on semi-solid media.
      The ctpA mutant also displayed an increased sensitivity to detergents, indicating
      an alteration in the permeability of the cell envelope. This is the first
      characterization of a ctpA gene within the Rhizobiaceae and the first report of a
      ctpA mutant that exhibits an increased sensitivity to desiccation.

PMID- 17456189
TI  - A proposed structural model of human protein Z.

PMID- 17456190
TI  - Treatment characteristics and the risk of inhibitor development: a multicenter
      cohort study among previously untreated patients with severe hemophilia A.
AB  - CONTEXT: The development of inhibitory antibodies against infused factor (F) VIII
      is a major complication of treatment of patients with severe hemophilia A.
      OBJECTIVE: This study was set up to examine the effects of treatment-related
      factors on inhibitor development among previously untreated patients with severe
      hemophilia A. DESIGN, SETTING AND PATIENTS: In this multicenter cohort study, we
      combined individual patient data obtained from four recombinant FVIII product
      registration studies (Kogenate, Kogenate Bayer, Recombinate, ReFacto) that were
      performed between 1989 and 2001. From the databases we selected all 236
      previously untreated patients with severe hemophilia A who were subsequently
      treated with FVIII on at least 50 days. MAIN OUTCOME MEASURES: Clinically
      relevant inhibitor development, defined as the occurrence of at least two
      positive inhibitor titers and a decreased recovery. RESULTS: 67 patients (28%)
      developed clinically relevant inhibitors (44 high-titer) at a median of ten
      exposure days. Age at first exposure was not associated with inhibitor
      development. Peak treatment moments and surgical procedures were related to an
      increased inhibitor risk [adjusted relative risk 1.6 (95% confidence interval 1.0
      2.6) and 2.7 (95% confidence interval 1.3-5.7), respectively]. A shorter duration
      between exposure days was associated with an increased risk of inhibitor
      development. There was a possible association between dosing of FVIII and
      inhibitor development, which largely disappeared after adjustment for confounding
      factors. INTERPRETATION: These findings show that intensive treatment periods are
      associated with an increased risk of inhibitor development in previously
      untreated patients with severe hemophilia A. Our results do not support the
      notion that age at first exposure is associated with the risk of developing
      inhibitors.

PMID- 17456191
TI  - Endothelial protein C receptor: location...with a pool!

PMID- 17456192
TI  - The greater in vivo antiplatelet effects of prasugrel as compared to clopidogrel
      reflect more efficient generation of its active metabolite with similar
      antiplatelet activity to that of clopidogrel's active metabolite.
AB  - BACKGROUND AND METHODS: Prasugrel is a novel orally active thienopyridine prodrug
      with potent and long-lasting antiplatelet effects. Platelet inhibition reflects
      inhibition of P2Y(12) receptors by its active metabolite (AM). Previous studies
      have shown that the antiplatelet potency of prasugrel is at least 10 times higher
      than that of clopidogrel in rats and humans, but the mechanism of its higher
      potency has not yet been fully elucidated. RESULTS: Oral administration of
      prasugrel to rats resulted in dose-related and time-related inhibition of ex vivo
      platelet aggregation, and its effect was about 10 times more potent than that of
      clopidogrel. The plasma concentration of prasugrel AM was higher than that of
      clopidogrel AM despite tenfold higher doses of clopidogrel, indicating more
      efficient in vivo production of prasugrel AM than of clopidogrel AM. In rat
      platelets, prasugrel AM inhibited in vitro platelet aggregation induced by
      adenosine 5'-diphosphate (ADP) (10 microm) with an IC(50) value of 1.8 microm.
      Clopidogrel AM similarly inhibited platelet aggregation with an IC(50) value of
      2.4 microm. Similar results were also observed for ADP-induced (10 microm)
      decreases in prostaglandin E(1)-stimulated rat platelet cAMP levels. These
      results indicate that both AMs have similar in vitro antiplatelet activities.
      CONCLUSIONS: The greater in vivo antiplatelet potency of prasugrel as compared to
      clopidogrel reflects more efficient in vivo generation of its AM, which
      demonstrates similar in vitro activity to clopidogrel AM.

PMID- 17456193
TI  - High levels of low-density lipoprotein cholesterol and triglycerides and
      suboptimal glycemic control predict diminished ex vivo aspirin responsiveness in
      patients with Type 2 diabetes.

PMID- 17456194
TI  - Protein C inhibitor directly and potently inhibits activated hepatocyte growth
      factor activator.
AB  - BACKGROUND: Hepatocyte growth factor (HGF) plays an important role in tissue
      repair and regeneration. HGF activator (HGFA), a factor XIIa-like serine
      protease, activates HGF precursor to HGF. The precursor of HGFA, proHGFA, is
      activated by thrombin generated at sites of tissue injury. It is known that
      protein C inhibitor (PCI), an inhibitor of activated protein C (APC), also
      inhibits thrombin-thrombomodulin (TM) complex. OBJECTIVES: In the present study
      we evaluated the effect of PCI on thrombin-catalyzed proHGFA activation in the
      presence of TM, and on HGFA activity. RESULTS: PCI did not inhibit thrombin-TM
      mediated proHGFA activation, but it directly inhibited activated HGFA by forming
      an enzyme inhibitor complex. The second-order rate constants (m(-1) min(-1)) of
      the reaction between HGFA and PCI in the presence or absence of heparin (10 U mL(
      1)) were 4.3 x 10(6) and 4.0 x 10(6), respectively. The inhibition of HGFA by PCI
      resulted in a significant decrease of HGFA-catalyzed activation of HGF precursor.
      Exogenous HGFA added to normal human plasma formed a complex with plasma PCI, and
      this complex formation was competitively inhibited by APC in the presence of
      heparin, but very weakly in the absence of heparin. We also demonstrated using
      recombinant R362A-PCI that Arg362 residue of PCI is important for HGFA inhibition
      by PCI as judged from the three-dimensional structures constructed using docking
      models of PCI and HGFA or APC. CONCLUSION: These observations indicate that PCI
      is a potent inhibitor of activated HGFA, suggesting a novel function for PCI in
      the regulation of tissue repair and regeneration.

PMID- 17456195
TI  - BK viral loads and immune monitoring in renal transplant recipients.

PMID- 17456196
TI  - Kidney allocation and the perception of fairness.

PMID- 17456197
TI  - Identification of gene markers for the prediction of allograft rejection or
      permanent acceptance.
AB  - The clinical success of new treatment strategies aiming on inducing permanent
      graft acceptance will rely on the ability to determine whether specific
      unresponsiveness to donor alloantigens has developed and for how long it is
      maintained. To identify markers for such posttransplant monitoring, genes
      differentially expressed by graft infiltrating leukocytes during tolerance
      induction or rejection after kidney transplantation in rats were compared. A
      subsequently performed full kinetic analysis in two different transplant models,
      kidney and heart, in two species, rat and mouse identified two markers (TOAG-1,
      alpha-1,2-mannosidase) with high specificity and reproducibility, which are
      highly expressed during induction and maintenance of acceptance, and
      downregulated during rejection. Expression level of these markers showed a strong
      positive correlation with graft function. In addition, expression of both genes
      was downregulated in the peripheral blood and the graft prior to rejection,
      suggesting that these markers may be useful for monitoring in clinical
      transplantation where peripheral blood is the most easily accessible patient
      sample. Interestingly, downregulation of TOAG-1 and alpha-1,2-mannosidase
      expression occurred in graft infiltrating cells and expression of both genes was
      also downregulated after T-cell activation in vitro.

PMID- 17456198
TI  - NIM811, a mitochondrial permeability transition inhibitor, prevents mitochondrial
      depolarization in small-for-size rat liver grafts.
AB  - ATP decreases markedly in small-for-size liver grafts. This study tested if the
      mitochondrial permeability transition (MPT) underlies dysfunction of small-for
      size livers. Half-size livers were implanted into recipients of about twice the
      donor weight, resulting in quarter-size liver grafts. NIM811 (5 microM), a
      nonimmunosuppressive MPT inhibitor was added to the storage solutions.
      Mitochondrial polarization and cell death were assessed by confocal microscopy of
      rhodamine 123 (Rh123) and propidium iodide (PI), respectively. After quarter-size
      transplantation, alanine aminotransferase (ALT), serum bilirubin and necrosis all
      increased. NIM811 blocked these increases by >70%. After 38 h, BrdU labeling, a
      marker of cell proliferation and graft weight increase were 3% and 5%,
      respectively, which NIM811 increased to 30% and 42%. NIM811 also increased
      survival of quarter-size grafts. In sham-operated livers, hepatocytes exhibited
      punctate Rh123 fluorescence. By contrast, in quarter-size grafts at 18 h after
      implantation, mitochondria of most hepatocytes did not take up Rh123, indicating
      mitochondrial depolarization. Nearly all hepatocytes not taking up Rh123
      continued to exclude PI at 18 h, indicating that depolarization preceded cell
      death. NIM811 and free radical-scavenging polyphenols strongly attenuated
      mitochondrial depolarization. In conclusion, mitochondria depolarized after
      quarter-size liver transplantation. NIM811 decreased injury and stimulated
      regeneration, probably by inhibiting free radical-dependent MPT onset.

PMID- 17456199
TI  - Adeno-associated viral vector-mediated interleukin-10 prolongs allograft survival
      in a rat kidney transplantation model.
AB  - Interleukin-10 (IL-10) is a pleiotropic cytokine that plays a pivotal role in the
      regulation of immune responses. Hence, we evaluated the effects of a recombinant
      adeno-associated viral vector 1 (rAAV1) encoding rat IL-10 (rAAV1-IL-10) in a rat
      model of kidney allograft rejection. Dark Agouti rat kidneys were transplanted
      into Wistar-Furth (WF) rats 8 weeks following a single intramuscular
      administration of either rAAV1-IL-10 or rAAV1-green fluorescence protein (GFP).
      Isografts (WF-WF) served as an additional experimental control. Both allograft
      and isograft recipients received daily cyclosporine (10 mg/kg) for 14 days after
      transplantation. Serum IL-10 levels increased at 8, 12 and 16 weeks following
      vector administration in rAAV1-IL-10-treated animals, but not in rAAV1-GFP and
      isograft groups. rAAV1-IL-10 treatment resulted in lower BUN and creatinine
      levels (p<0.001), as well as increased allograft survival rates from 22% to 90%.
      Allograft histological abnormalities were significantly attenuated in the rAAV1
      IL-10-treated rats compared with those of rAAV1-GFP controls. Serum levels of
      proinflammatory cytokines such as growth-related oncogene were also significantly
      higher in the rAAV1-GFP group than in the rAAV1-IL-10 group. These data suggest
      delivery of IL-10 using a rAAV1 vector improves renal function and prolongs graft
      survival in a rat model of kidney transplant rejection.

PMID- 17456200
TI  - Early loss of renal transcripts in kidney allografts: relationship to the
      development of histologic lesions and alloimmune effector mechanisms.
AB  - We sought to understand the epithelial response to the T-cell mediated
      inflammatory process in kidney allograft rejection. Using microarrays, we studied
      transcriptome changes of kidney parenchymal cells and their relationship to the
      development of pathologic lesions such as tubulitis in mouse kidney allografts
      and isografts. Inflammatory infiltrate in allografts developed by day 5, but
      tubulitis first appeared at day 7 and was severe by day 21. Using microarrays, we
      selected 70 solute carrier transcripts with high renal parenchymal expression and
      known epithelial function. Transcript expression was reduced early in isografts
      and allografts, followed by progressive loss in allografts and recovery in
      isografts. The expression pattern of day 21 allografts developed progressively
      from the time of engraftment and was established before histologic lesions. These
      changes are probably functionally significant: selected proteins showed decreased
      immunostaining at days 7 and 21. Allospecific loss of transcripts was dependent
      on T cells but independent of perforin, granzymes A/B, CD103, or B cells.
      Weighted sum decomposition revealed multiple components of the epithelial
      response with allospecific changes from day 1. We conclude that loss of renal
      transcripts indicates an early stage of T-cell mediated alloimmune injury that
      later progresses to pathologic lesions such as tubulitis.

PMID- 17456201
TI  - Pretransplant HLA antibodies are associated with reduced graft survival after
      clinical islet transplantation.
AB  - Despite significant improvements in islet transplantation, long-term graft
      function is still not optimal. It is likely that both immune and nonimmune
      factors are involved in the deterioration of islet function over time.
      Historically, the pretransplant T-cell crossmatch and antibody screening were
      done by anti-human globulin--complement-dependent cytotoxicity (AHG-CDC). Class
      II antibodies were not evaluated. In 2003, we introduced solid-phase antibody
      screening using flow-based beads and flow crossmatching. We were interested to
      know whether pretransplant human leukocyte antigen (HLA) antibodies or a positive
      flow crossmatch impacted islet function post-transplant. A total of 152 islet
      transplants was performed in 81 patients. Islet function was determined by a
      positive C-peptide. Results were analyzed by procedure. Class I and class II
      panel reactive antibody (PRA) > 15% and donor-specific antibodies (DSA) were
      associated with a reduced C-peptide survival (p<0.0001 and p<0.0001,
      respectively). A positive T- and or B-cell crossmatch alone was not.
      Pretransplant HLA antibodies detectable by flow beads are associated with reduced
      graft survival. This suggests that the sirolimus and low-dose tacrolimus-based
      immunosuppression may not control the alloimmune response in this presensitized
      population and individuals with a PRA > 15% may require more aggressive inductive
      and maintenance immunosuppression, or represent a group that may not benefit from
      islet transplantation.

PMID- 17456202
TI  - The effect of recipient's age on lung transplant outcome.
AB  - Selection criteria for organ transplantation have evolved over time. Age has been
      revisited periodically. We studied the outcome of lung transplant adjusted by age
      in a single center transplant population. We matched the 42 lung graft recipients
      older than 60 years transplanted by July 1999 to younger controls by lung
      disease, transplant era within 2 years, type of transplant and gender. The female
      to male ratios were 17/25 among the older cohort (median age 61.6 years), and
      15/27 (median age 51.9 years) among the matched younger. Survival analysis
      demonstrated a significant difference: at 1 year, 60% versus 86%, and at 5 years,
      37% versus 57%, for older and younger, respectively, p=0.005. Excess annual
      mortality, calculated with the declining exponential approximation to life
      expectancy (DEALE), showed an older/younger ratio of 1.9. Eleven deaths occurred
      within 6 months among the older patients, 10 due to infection. After 6 months,
      there were 20 more deaths, 6 due to malignancy, 5 to Bronchiolitis Obliterans
      Syndrome (BOS), 3 to infection and 6 to other causes. Among the younger there
      were 6 deaths within 6 months and 12 more thereafter; among the latter, 8 were
      due to BOS. Despite stringent selection, lung transplant recipients older than 60
      years show increased mortality even after adjusting for their expected higher age
      related mortality.

PMID- 17456203
TI  - Transient airway colonization is associated with airway inflammation after lung
      transplantation.
AB  - Lower airway tract colonization may trigger neutrophil-mediated airway
      inflammation. We investigated whether transient airway colonization influences
      airway inflammation and pulmonary function after lung transplantation (LTx). In
      this retrospective study, stable LTx patients with consecutive broncho-alveolar
      lavages (BAL), the first colonized and the second noncolonized, were included to
      create a Pooled group (P, n=32) and a Gram Negative (GN, n=14), Gram Positive
      (GP, n=9) and Fungi (F, n=9) subgroup. Similarly, LTx patients with consecutive,
      noncolonized BAL samples were included as Control group (C, n=19). BAL analysis
      (cell counts, IL6, IL8) and forced expiratory volume (FEV(1)) were compared
      between groups. In the P group and the GN subgroup, colonized BAL samples showed
      a significant increase in total cells, neutrophilia and IL8-concentration and a
      significant decrease in FEV(1), even when compared with the matched samples of
      the C group. A significant increase in neutrophilia was observed in the GP
      subgroup, but no other significant difference was found either in the GP and F
      subgroup or the C group. IL6 levels were not significantly different between
      groups. Transient airway colonization, especially with Pseudomonas-like GN
      bacteria, in stable LTx patients may be associated with IL8-dependent
      neutrophilic airway inflammation and a, albeit subtle, decrease in FEV(1).

PMID- 17456204
TI  - Another missed opportunity: routine recovery of cadaveric organs.

PMID- 17456205
TI  - Is lymphoid neogenesis a therapeutic target for chronic rejection?

PMID- 17456209
TI  - Towards rationalizing the nomenclature and classification of urticaria: some
      guidance on guidelines.

PMID- 17456210
TI  - Unpasteurized milk: health or hazard?

PMID- 17456211
TI  - BSACI guidelines for the management of chronic urticaria and angio-oedema.
AB  - This guidance for the management of patients with chronic urticaria and angio
      oedema has been prepared by the Standards of Care Committee (SOCC) of the British
      Society for Allergy and Clinical Immunology (BSACI). The guideline is based on
      evidence as well as on expert opinion and is aimed at both adult physicians and
      paediatricians practising in allergy. The recommendations are evidence graded.
      During the development of these guidelines, all BSACI members were included in
      the consultation process using a web-based system. Their comments and suggestions
      were carefully considered by the SOCC. Where evidence was lacking a consensus was
      reached by the experts on the committee. Included in this guideline are clinical
      classification, aetiology, diagnosis, investigations, treatment guidance with
      special sections on children with urticaria, and the use of antihistamines in
      women who are pregnant or breastfeeding. Finally, we have made recommendations
      for potential areas of future research.

PMID- 17456212
TI  - Food anaphylaxis.
AB  - Anaphylaxis is a life-threatening allergic reaction, and food is one of the most
      common responsible allergens in the outpatient setting. The prevalence of food
      induced anaphylaxis has been steadily rising. Education regarding food allergen
      avoidance is crucial as most of the fatal reactions occurred in those with known
      food allergies. The lack of a consensus definition for anaphylaxis has made its
      diagnosis difficult. Symptoms affect multiple organ systems and include pruritus,
      urticaria, angioedema, vomiting, diarrhoea, abdominal cramps, respiratory
      difficulty, wheezing, hypotension, and shock. Prompt recognition of anaphylaxis
      is essential as delayed treatment has been associated with fatalities. Although
      epinephrine is accepted as the treatment of choice, timely administration does
      not always occur, partly due to a lack of awareness of the diagnostic criteria.
      Several novel tools are currently being investigated, which will potentially aid
      in the diagnosis and treatment of food-induced anaphylaxis.

PMID- 17456213
TI  - Inverse association of farm milk consumption with asthma and allergy in rural and
      suburban populations across Europe.
AB  - BACKGROUND: Dietary interventions as a means for atopy prevention attract great
      interest. Some studies in rural environments claimed an inverse association
      between consumption of farm-produced dairy products and the prevalence of
      allergic diseases, but current evidence is controversial. OBJECTIVE: To
      investigate whether consumption of farm-produced products is associated with a
      lower prevalence of asthma and allergy when compared with shop-purchased
      products. METHODS: Cross sectional multi-centre study (PARSIFAL) including 14,893
      children aged 5-13 years from five European countries (2823 from farm families
      and 4606 attending Steiner Schools as well as 5440 farm reference and 2024
      Steiner reference children). A detailed questionnaire including a dietary
      component was completed and allergen-specific IgE was measured in serum. RESULTS:
      Farm milk consumption ever in life showed a statistically significant inverse
      association with asthma: covariate adjusted odds ratio (aOR) 0.74 [95% confidence
      interval (CI) 0.61-0.88], rhinoconjunctivitis: aOR 0.56 (0.43-0.73) and
      sensitization to pollen and the food mix fx5 (cut-off level of >or=3.5 kU/L): aOR
      0.67 (0.47-0.96) and aOR 0.42 (0.19-0.92), respectively, and sensitization to
      horse dander: aOR 0.50 (95% CI 0.28-0.87). The associations were observed in all
      four subpopulations and independent of farm-related co-exposures. Other farm
      produced products were not independently related to any allergy-related health
      outcome. CONCLUSION: Our results indicate that consumption of farm milk may offer
      protection against asthma and allergy. A deepened understanding of the relevant
      protective components of farm milk and a better insight into the biological
      mechanisms underlying this association are warranted as a basis for the
      development of a safe product for prevention.

PMID- 17456214
TI  - The association between infant feeding practices and subsequent atopy among
      children with a family history of asthma.
AB  - BACKGROUND: Although longer duration of breastfeeding and later introduction of
      solid foods are both recommended for the prevention of asthma and allergic
      disease, evidence to support these recommendations is controversial. OBJECTIVE:
      To examine the relation between infant feeding practices and the risk of asthma
      and allergic disease at age 5 years. METHODS: A cohort of children with a family
      history of asthma in Sydney, Australia, was followed from birth to age 5 years.
      Data on infant feeding practices and on early manifestations of eczema were
      collected prospectively. The presence of eczema, asthma and atopy (positive
      allergen skin prick tests) were determined at age 5 years. RESULTS: In 516
      children evaluated at age 5 years, there was no significant association between
      the duration of breastfeeding or timing of introduction of solid foods and
      protection against asthma or other allergic disease, after adjustment for
      confounding factors. However, breastfeeding for 6 months or more and introduction
      of solid foods after 3 months were both associated with an increased risk of
      atopy at age 5 years (P=0.02 and 0.01, respectively). There was no significant
      association between the presence of eczema at 4 weeks and at 3 months and
      continued breastfeeding beyond those times. CONCLUSION: Longer duration of
      breastfeeding and later introduction of solid foods did not prevent the onset of
      asthma, eczema or atopy by age 5 years.

PMID- 17456215
TI  - Interaction of maternal atopy, CTLA-4 gene polymorphism and gender on antenatal
      immunoglobulin E production.
AB  - BACKGROUND: Genetic heritability and maternal atopy have been correlated to
      antenatal IgE production, but very few studies have studied gene-maternal atopy
      interaction on antenatal IgE production. This study investigated the interaction
      of CTLA-4 polymorphism with prenatal factors on the elevation of cord blood IgE
      (CBIgE). METHODS: Pregnant women were antenatally recruited for collection of
      prenatal environmental factors by a questionnaire. Umbilical cord blood samples
      were collected for CBIgE detection by fluorescence-linked enzyme assay and CTLA-4
      polymorphism measurement by restriction fragment length polymorphism. RESULTS: A
      total of 1104 pregnant women initially participated in this cohort study, and 898
      of them completed cord blood collection. 21.4% of the newborns had elevation of
      CBIgE (>or=0.5 kU/L). The CTLA-4+49A allele (P=0.021), maternal atopy (P<0.001)
      and gender (P=0.034), but not the CTLA-4+49G allele, -318C allele, -318T allele,
      parental smoking or paternal atopy, were significantly correlated with the CBIgE
      elevation in multivariate analysis. A dichotomous analysis of gene-maternal atopy
      interactions identified maternal atopy and CTLA-4+49A allele had an additive
      effect on the CBIgE elevation, especially prominent in male newborns; and in the
      absence of maternal atopy, CTLA-4+49GG genotype had a protective effect on CBIgE
      elevation in female newborns. CONCLUSIONS: Maternal but not paternal atopy has
      significant impacts on CBIgE elevation depending on gender and CTLA-4+49A/G
      polymorphism of newborns. Control of maternal atopy and modulation of CTLA-4
      expression in the prenatal stage may be a target for the early prevention of
      perinatal allergy sensitization.

PMID- 17456216
TI  - Lower airways inflammation in allergic rhinitics: a comparison with asthmatics
      and normal controls.
AB  - BACKGROUND: Allergic rhinitis (AR) and asthma represent a continuum of atopic
      disease. AR is believed to pre-dispose an individual to asthma. Compared with
      asthmatics and normal controls, the inflammatory response in the lower airways of
      rhinitics is not fully elucidated. To test the hypothesis that the inflammatory
      response in the airways of subjects with AR is at a level intermediate between
      that in normal controls and asthmatics, we have characterized bronchial
      inflammation and cytokine mRNA levels in non-asthmatic allergic rhinitics and
      compared it with subjects with allergic asthma and with normal controls. METHODS:
      Endobronchial mucosal biopsies were obtained at bronchoscopy from 14 allergic
      rhinitics, 16 asthmatics and 21 normal controls. Biopsies were embedded into
      glycol methacrylate resin for immunohistochemical analysis of cellular
      inflammation and snap frozen for semi-quantitative PCR analysis of cytokine mRNA
      levels. RESULTS: Airway inflammation in rhinitic subjects was characterized by an
      increase in submucosal eosinophils, mast cells and the mRNA expression of TNF
      alpha, at an intermediate level between healthy and asthmatics. In addition,
      CD3(+) and CD8(+) lymphocytes in the epithelium, the endothelial expression of
      vascular adhesion molecule-1 and IL-1 beta mRNA were higher in the allergic
      rhinitics compared with both normal controls and asthmatics, whereas growth
      related oncogene alpha-mRNA was decreased in AR compared with both healthy and
      asthmatics. Airway inflammation in the asthmatic group was characterized by
      higher numbers of eosinophils and mast cells, together with an increase in TNF
      alpha-mRNA compared with both healthy and rhinitics. IFN-gamma mRNA was the
      highest in normal controls and lowest in the asthmatics. CONCLUSIONS: In
      individuals with AR the present data suggest an intermediate state of airway
      inflammation between that observed in normal individuals and subjects with
      clinical asthma. It is also indicated that IFN-gamma production by CD8(+) T
      lymphocytes could be protective against the development of airway
      hyperresponsiveness. Further work is needed to evaluate this hypothesis.

PMID- 17456217
TI  - A proof-of-concept study to assess the putative dose response to topical
      corticosteroid in persistent allergic rhinitis using adenosine monophosphate
      challenge.
AB  - INTRODUCTION: The aim of this proof-of-concept study was to assess whether nasal
      adenosine monophosphate (AMP) challenge may be used to quantify dose response to
      topical fluticasone propionate (FP) in persistent allergic rhinitis (PER).
      METHODS: Eligible subjects with PER entered a randomized double-blind crossover
      study of 2 weeks of intranasal FP at 100 microg or 400 microg daily, with a 2
      week placebo washout period before each randomized treatment. Measurements after
      each washout or treatment comprised: peak nasal inspiratory flow (PNIF) response
      to nasal AMP (the primary outcome), domiciliary PNIF, the mini
      rhinoconjunctivitis quality of life questionnaire (miniRQLQ), symptom scores,
      nasal nitric oxide levels and overnight urinary cortisol:creatinine ratios.
      RESULTS: Thirteen patients completed per protocol. Maximal PNIF response to AMP
      was attenuated 0.9% (95% confidence interval -7.1 to 9.0, P=NS) by FP 100 microg,
      and 12.9% (4.8-20.9, P=0.009) by FP 400 microg. The 400-100 microg difference was
      12.0% U (2.6-21.3, P=0.049). None of the other outcomes were responsive enough to
      detect any significant treatment effects. The standardized response means to FP
      400 microg were 81% for AMP challenge, 54% for domiciliary PNIF, 53% for
      miniRQLQ, 24% for symptom scores and 18% for nasal nitric oxide. No adrenal
      suppression was detected at either dose. CONCLUSION: FP exhibited dose-related
      suppression of nasal airway hyperresponsiveness to AMP challenge, but without
      associated detectable adrenal suppression at the higher dose. Moreover, the AMP
      response demonstrated the highest signal to noise ratio compared with other
      outcome measures in PER.

PMID- 17456218
TI  - Up-regulation of CCL17, CCL22 and CCR4 in drug-induced maculopapular exanthema.
AB  - BACKGROUND: Maculopapular exanthema has been reported to be the most frequently
      drug-induced cutaneous reaction. Although T lymphocytes are involved in the
      pathomechanism of this disease, little is know about the recruitment of these
      cells to the skin. OBJECTIVE: The aim of this work is to study the role of the
      chemokines TARC/CCL17 and MDC/CCL22 in the lymphocyte trafficking to affected
      skin in drug-induced exanthemas. METHODS: Real-time PCR was performed to quantify
      gene expression levels of CCL17, CCL22 and their receptor CCR4 in lesional skin
      biopsies and in peripheral blood mononuclear cells from patients. CCL27 and CCL22
      proteins were detected in the skin by immunochemistry. Protein expression of CCR4
      was determined by flow cytometry in peripheral blood lymphocytes. Functional
      migration assays to CCL17 and CCL22 were assessed to compare the migratory
      responses of peripheral blood lymphocytes from patients and healthy subjects.
      RESULTS: CCL17 and CCL22 were up-regulated in maculopapular exanthema-affected
      skin. CCR4 mRNA levels and protein expression were increased in peripheral blood
      mononuclear cells during the acute phase of the disease. The increased expression
      of the receptor was consistent with a higher response of peripheral blood
      lymphocytes to CCL17 and CCL22 compared with the migratory response in healthy
      donors. CONCLUSION: TARC/CCL17 and MDC/CCL22 might cooperate in attracting T
      lymphocytes to skin in drug-induced maculopapular exanthemas.

PMID- 17456219
TI  - Inhibitory effects of N-acetylcysteine on the functional responses of human
      eosinophils in vitro.
AB  - BACKGROUND: Oxidative stress appears to be relevant in the pathogenesis of
      inflammation in allergic diseases like bronchial asthma. Eosinophils are oxidant
      sensitive cells considered as key effectors in allergic inflammation. OBJECTIVE:
      The aim of this work was to study the effects of the clinically used antioxidant
      N-acetyl-L-cysteine (NAC) on the functional responses of human-isolated
      eosinophils. METHODS: Human eosinophils were purified from the blood of healthy
      donors by a magnetic bead separation system. The effects of NAC were investigated
      on the generation of reactive oxygen species (chemiluminescence and flow
      cytometry), Ca(2+) signal (fluorimetry), intracellular glutathione (GSH; flow
      cytometry), p47(phox)-p67(phox) translocation (Western blot) and eosinophil
      cationic protein (ECP) release (radioimmunoassay). RESULTS: NAC (0.1-1 mm)
      inhibited the extracellular generation of oxygen species induced by N-formyl-L
      methionyl-L-leucyl-L-phenylalanine (fMLP) and eotaxin (in the presence of IL-5)
      with -logIC(50) values of 3.61+/-0.03 and 3.36+/-0.09, respectively. Also, the
      intracellular generation of hydrogen peroxide was virtually abolished by NAC (0.5
      1 mm). NAC (1 mm) did not alter the fMLP-induced Ca(2+) signal but augmented the
      eosinophil content of reduced GSH and inhibited p47(phox)-p67(phox)
      translocation. NAC inhibited the release of ECP ( approximately 90% inhibition at
      1 mm) from fMLP-activated eosinophils. CONCLUSION: Inhibition by NAC of human
      eosinophil functions in vitro is potentially useful in the treatment of allergic
      inflammation.

PMID- 17456220
TI  - Interference of methysergide, a specific 5-hydroxytryptamine receptor antagonist,
      with airway chronic allergic inflammation and remodelling in a murine model of
      asthma.
AB  - BACKGROUND: Airway remodelling encompasses the structural changes observed in
      asthmatic airways. Mast cells, through the release of histamine and 5
      hydroxytryptamine (serotonin), are implicated in early asthmatic reactions,
      bronchoconstriction and mucosal oedema, and in the development of bronchial
      hyperresponsiveness. However, the association between serotonin and remodelling
      processes in murine model of airways inflammation remains to be elucidated.
      OBJECTIVE: As serotonin is released by murine mast cells upon antigen challenge,
      we tested the hypothesis of its involvement in the development of inflammatory
      and remodelling processes in a murine model of chronic airway inflammation
      following prolonged allergen challenge. Methods BALB/c mice were exposed to
      aerosolized ovalbumin for 20 min 2 days a week, for 4 consecutive weeks. Two
      hours before each challenge, they were treated with methysergide (intranasally,
      40 microg/kg). Forty-eight hours after the last aerosol challenge,
      bronchoalveolar lavage (BAL) and lung tissue were collected for analysis.
      RESULTS: Methysergide inhibited the allergen-induced increase in airway
      eosinophilia, reduced T helper type 2 (Th2) cytokines in lung, spleen or thoracic
      lymph nodes, and specific IgE levels. The extravasation of plasma and fibronectin
      production in the lung, and collagen deposition in the lung were also inhibited
      after methysergide treatment. Although methysergide treatment induced an increase
      in IFN-gamma levels, experiments with neutralizing antibody suggest that this is
      not responsible for inhibition. In addition, instillation of serotonin to
      immunized mice induced eosinophil recruitment to BAL, Th2 cytokine production and
      fibronectin release in lung as well as collagen deposition. CONCLUSION: Serotonin
      may contribute to the development and maintenance of remodelling through the
      release of cytokines and of fibrogenic mediators. Serotonin should therefore be
      considered as relevant for the development and maintenance of airway remodelling.

PMID- 17456221
TI  - Overexpression of suppressor of cytokine signalling-5 augments eosinophilic
      airway inflammation in mice.
AB  - BACKGROUND: Enhanced expression of the suppressor of cytokine signalling (SOCS)-5
      might be of therapeutic benefit for T-helper type 2 (Th2) dominant diseases, as
      its expression is reported to result in a reduction of Th2 differentiation in
      vitro due to the inhibition of IL-4 signalling. OBJECTIVE: To investigate the
      regulatory role of SOCS-5 in vivo, we explored the phenotype of an experimental
      asthma model developed in SOCS-5 transgenic (Tg) mice. METHODS: The SOCS-5 Tg
      mice or wild-type (WT) mice were sensitized and repeatedly challenged with
      ovalbumin (OVA). We examined bronchoalveolar lavage fluid (BALF), lung specimens,
      and airway hyperresponsiveness (AHR) to methacholine. RESULTS: The production of
      IFN-gamma by CD4(+) T cells from unprimed SOCS-5 Tg mice was significantly
      increased in comparison with unprimed wild-type mice, indicating that SOCS-5 Tg
      mice have a Th1-polarizing condition under natural conditions. However, in an
      asthma model, significantly more eosinophils in the airways and higher levels of
      IL-5 and IL-13 in BALF were observed in the SOCS-5 Tg than the wild-type mice.
      AHR in the asthma model of SOCS-5 Tg was also more enhanced than that of wild
      type mice. OVA-stimulated CD4(+) T cells from the primed SOCS-5 Tg mice produced
      significantly more IL-5 and IL-13 than CD4(+) T cells from wild-type mice.
      CONCLUSION: Our results demonstrate that the overexpression of SOCS-5 does not
      inhibit Th2 response, but rather augments the phenotype of the asthma model in
      vivo. This finding throws into question the therapeutic utility of using
      enhancement of SOCS-5 expression for Th2-dominant disease.

PMID- 17456222
TI  - Lipopolysaccharide promotes and augments metal allergies in mice, dependent on
      innate immunity and histidine decarboxylase.
AB  - BACKGROUND: Few adequate murine models exist for metal allergies, it being
      especially difficult to induce Ni allergy in mice. OBJECTIVE: We examined the
      effect of lipopolysaccharide (LPS) on allergies to Ni and other metals in mice.
      METHODS: Ten days after sensitization with a metal salt and LPS, the ears were
      challenged with the same metal salt. RESULTS: LPS+NiCl(2) (1 mM) was effective at
      sensitizing mice to Ni, LPS being effective at very low concentrations whether
      injected intradermally or intraperitoneally. The ear-swelling response to Ni was
      more severe and more rapid in C57BL/6 mice than in BALB/c mice. In mast-cell
      deficient mice, TNF-alpha-deficient mice, and interestingly even in nude (T cell
      deficient) mice, NiCl(2)+LPS induced a Ni allergy similar in degree to that in
      the respective control mice, but it induced Ni allergy only weakly in TLR4-mutant
      mice, macrophage-depleted mice, and IL-1-deficient mice. The activity of the
      histamine-forming enzyme histidine decarboxylase (HDC) in the ears increased in
      parallel with ear swelling, and HDC-deficient mice were resistant to ear
      swelling. Challenge with NiCl(2)+LPS augmented ear swelling (vs. NiCl(2) alone).
      LPS induced effective sensitization to other metals (Cr, Co, Pd, or Ag).
      CONCLUSIONS: These results indicate that in mice, LPS is a very important inducer
      of metal allergies, and potently promotes them (dependent on both innate immunity
      and HDC induction in cells other than mast cells). We discussed the idea that the
      bacterial environment is important for the establishment of metal allergies and
      for their provocation, and that the current thinking (including the contribution
      of T cells) should be reappraised in future studies.

PMID- 17456223
TI  - Contribution of Ara h 2 to peanut-specific, immunoglobulin E-mediated, cell
      activation.
AB  - BACKGROUND: Ara h 2 is a potent peanut allergen but its contribution to the
      ability of a crude peanut extract (CPE) to cross-link IgE and activate mast cells
      has not been rigorously evaluated. OBJECTIVE: To measure the contribution that
      Ara h 2 makes to the effector function of a CPE. METHODS: Ara h 2 was
      specifically removed from a CPE as demonstrated by immunoblots, 2D gels, and an
      inhibitory ELISA. Functional assays of sham-treated and Ara h 2-depleted CPEs
      were performed with RBL SX-38 cells sensitized with IgE from highly peanut
      allergic subjects and with naturally sensitized basophils. RESULTS: Depletion of
      approximately 99% of the Ara h 2 from the CPE led to an increase in the
      concentration of the CPE necessary to give 50% of maximal degranulation (EC50) of
      the SX-38 cells following sensitization with sera that contain anti-Ara h 2 IgE.
      Assays with a pool of 10 sera showed a small but significant increase in the EC50
      following depletion of Ara h 2 (1.65+/-0.15-fold; P<0.05) and assays of seven
      individual sera showed a similar increase in the average EC50 (1.7+/-0.2-fold;
      P<0.02). The percent of the anti-peanut IgE that binds Ara h 2 correlated with an
      increase in the EC50 of the CPE following depletion of Ara h 2 (r=0.83; P<0.02).
      On the other hand, data from three of these patients studied with a basophil
      histamine release assay did not show a significant effect of depletion of Ara h
      2. CONCLUSION: Based on its ability to cross-link IgE effectively, Ara h 2 is
      clearly an important peanut allergen. Its ability to cross-link IgE effectively
      from a specific serum is related to the proportion of anti-Ara h 2 in that serum
      but Ara h 2 does not account for a majority of the effector activity of the CPE
      for any of the sera studied.

PMID- 17456224
TI  - A matrix effect in pectin-rich fruits hampers digestion of allergen by pepsin in
      vivo and in vitro.
AB  - BACKGROUND: It is a general belief that a food allergen should be stable to
      gastric digestion. Various acidic plant polysaccharides, including pectin, are
      ubiquitous in fruit matrixes and can form hydrogels under low-pH conditions.
      OBJECTIVE: The purpose of this study was to investigate the effect of hydrogel
      forming polysaccharide-rich fruit matrixes on in vivo gastric and in vitro pepsic
      digestion of fruit allergens. METHODS: Fruit extract proteins (kiwi, banana,
      apple and cherry) and a purified major kiwi allergen Act c 2 were digested with
      simulated gastric fluid in accordance with the US Pharmacopeia. In vivo
      experiments on kiwi fruit digestion were performed on four healthy non-atopic
      volunteers by examining the gastric content 1 h after ingestion of kiwi fruit.
      The Act c 2 and kiwi proteins were detected in immunoblots using monoclonal anti
      Act c 2 antibodies and rabbit polyclonal antisera. RESULTS: Crude fruit extracts
      were resistant to digestion by pepsin when compared with commonly prepared
      extracts. In the gastric content of all volunteers, following kiwi fruit
      ingestion and immunoblotting, intact Act c 2 was detected with anti-Act c 2
      monoclonal antibodies, while kiwi proteins of higher molecular weights were
      detected using rabbit polyclonal antisera. Addition of apple fruit pectin (1.5%
      and 3%) to the purified kiwi allergen was able to protect it from pepsin
      digestion in vitro. CONCLUSION: The matrix effect in pectin-rich fruits can
      influence the digestibility of food proteins and thereby the process of allergic
      sensitization in atopic individuals.

PMID- 17456225
TI  - Cost-effectiveness of grass allergen tablet (GRAZAX) for the prevention of
      seasonal grass pollen induced rhinoconjunctivitis - a Northern European
      perspective.
AB  - BACKGROUND: The prevalence of allergic rhinoconjunctivitis has increased
      dramatically. Seventeen million people in the United Kingdom, Germany, the
      Netherlands, Sweden, Denmark, Norway and Finland suffer from grass pollen induced
      allergic rhinitis. Symptomatic therapy with antihistamines and topical steroids
      is partially effective but allergen-specific immunotherapy by injection or
      sublingual routes is superior. The grass allergen tablet (GRAZAX) is a new
      allergen-specific immunotherapy for home administration. OBJECTIVE: To assess the
      cost-effectiveness of the grass allergen tablet compared with symptomatic
      medication in seven Northern European countries. METHODS: A prospective
      pharmacoeconomic analysis was carried out alongside a multinational clinical
      trial. Pooled data on resource use and health outcomes were collected. A societal
      perspective was adopted, and the analysis had a 9-year time horizon. The outcome
      measure was Quality Adjusted Life Years (QALYs). RESULTS: The grass allergen
      tablet was clinically superior to symptomatic treatment, producing statistically
      significant differences for all efficacy end-points, including the number of
      QALYs gained - 0.976 vs. 0.947 QALYs gained. There was a significantly higher
      usage of the rescue medications loratadine and budesonide, and more hours missed
      from work (production loss), in the symptomatic treatment group. The cost per
      QALY gained in the grass allergen tablet group was similar in the seven countries
      (euro 12,930 to euro 18,263 for an annual cost of the grass allergen tablet of
      euro 1500). The analysis showed that the grass allergen tablet was cost-effective
      for all countries for an annual treatment cost below euro 2200. CONCLUSION: The
      pharmacoeconomic analysis illustrated that allergen-specific immunotherapy with
      the grass allergen tablet is a cost-effective intervention for the prevention of
      grass pollen induced rhinoconjunctivitis in Northern European countries, for a
      tablet price below euro 6. In Germany for example the price of the tablet is euro
      2.95 corresponding to a yearly treatment cost of euro 358 - based on a 9-year
      time horizon.

PMID- 17456226
TI  - Number of allergens to be tested to assess allergenic sensitization in
      epidemiologic studies: results of the European Community Respiratory Health
      Survey I.
AB  - BACKGROUND: Many clinical and epidemiological studies have measured the
      prevalence of IgE sensitization using skin tests and/or serum-specific IgE. Most
      of them have been done in only one country using a battery of selected allergens
      relevant to that country. In multi-centre studies, the number of tested allergens
      is often limited by the cost. It is therefore difficult to compare prevalence of
      sensitized subjects between studies. OBJECTIVE: To define the number and the type
      of allergen that should be tested in order to characterize a person as
      sensitized. METHOD: Subjects were selected from the European Community
      Respiratory Health Survey I. All subjects underwent skin prick tests to nine of
      the most common allergens. In addition, two local allergens were tested in some
      centres. RESULT: Using nine allergens, 35.6% of the 11 355 subjects were
      sensitized. The prevalence of sensitization increased with the number of tested
      allergens. Seven allergens enabled the identification of almost all sensitized
      subjects, adding another one inducing, in most countries, an increase of
      prevalence under 0.5%. Adding one local allergen to the battery of tests
      increased the overall estimated prevalence by only 1%. This increase was not seen
      in Ireland and was less marked in the United Kingdom (0.3%) but was greater in
      France (2.6%), Australia (2.5%) and Belgium (1.9%). CONCLUSION: Seven selected
      allergens (Dermatophagoides pteronyssinus, cat, grass, birch, olive pollen,
      Alternaria and Cladosporium) allow the identification of almost all sensitized
      subjects in epidemiologic studies. Inclusion of local allergen should be
      considered in a standard panel for international studies.

PMID- 17456227
TI  - Allergic rhinitis and asthma ad hoc survey: clinical and psychological
      perspectives.
AB  - BACKGROUND: Several studies have provided evidence of a strong association
      between asthma and rhinitis, with consequences in terms of therapy and disease
      management. OBJECTIVES: The aims of our study were to evaluate physicians'
      knowledge about rhinitis/asthma comorbidity, to note the patients' management
      behaviour and to assess the patients' experience about symptoms and expectations,
      and to investigate the clinical and psychological meaning of general
      practitioners' and patients' awareness. METHODS: One hundred and one general
      practitioners and 504 asthmatic patients participated in the study. General
      practitioners and patients filled in two different multiple choice questionnaires
      concerning asthma-rhinitis link and impact. RESULTS: 34.7% of general
      practitioners are aware of the link between asthma and rhinitis, and 43.6% of
      them hypothesize the comorbidity on the basis of their clinical experience. 21.8%
      of physicians make the diagnosis autonomously. 27.8% of asthmatic patients
      experience three or less rhinitic symptoms, 41% from four to six symptoms and
      31.2 more than six symptoms. These symptoms deeply interfere with daily life,
      causing sleep problems (87.3%), lack of concentration (78.9%), difficulties in
      spare time (71.8%) and sport (71.7%). Rhinitis symptoms are responsible for the
      worsening of asthma, with an increase in dyspnoea (86.3%), cough (73.9%), and
      wheezing (59%). Ninety-three percent of patients expressed an interest in a
      combination therapy approach. CONCLUSIONS: Asthma and rhinitis interact in the
      development of clinical burden and impact on quality of life. The survey results
      showed different perspectives when evaluated from clinical and psychological
      points of view.

PMID- 17456228
TI  - Understanding the potential role of mobile phone-based monitoring on asthma self
      management: qualitative study.
AB  - BACKGROUND: National and international healthcare policy increasingly seeks
      technological solutions to the challenge of providing care for people with long
      term conditions. Novel technologies, however, have the potential to change the
      dynamics of disease monitoring and self-management. We aimed to explore the
      opinions and concerns of people with asthma and primary care clinicians on the
      potential role of mobile phone monitoring technology (transmitting symptoms and
      peak flows, with immediate feedback of control and reminder of appropriate
      actions) in supporting asthma self-management. METHODS: This qualitative study
      recruited 48 participants (34 adults and teenagers with asthma, 14 asthma nurses
      and doctors) from primary care in Lothian (Central Scotland) and Kent (South East
      England). Thirty-nine participated in six focus groups, which included a
      demonstration of the technology; nine gave in-depth interviews before and after a
      4-week trial of the technology. RESULTS: Participants considered that mobile
      phone-based monitoring systems can facilitate guided self-management although,
      paradoxically, may engender dependence on professional/technological support. In
      the early phases, as patients are learning to accept, understand and control
      their asthma, this support was seen as providing much-needed confidence. During
      the maintenance phase, when self-management predominates, patient and
      professionals were concerned that increased dependence may be unhelpful, although
      they appreciated that maintaining an on-going record could facilitate
      consultations. CONCLUSION: Mobile phone-based monitoring systems have the
      potential to support guided self-management by aiding transition from clinician
      supported early phases to effective self-management during the maintenance phase.
      Continuing development, adoption and formal evaluation of these systems should
      take account of the insights provided by our data.

PMID- 17456229
TI  - Screening of the transcriptional regulatory regions of vascular endothelial
      growth factor receptor 2 (VEGFR2) in amyotrophic lateral sclerosis.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) has neurotrophic activity
      which is mediated by its main agonist receptor, VEGFR2. Dysregulation of VEGF
      causes motor neurone degeneration in a mouse model of amyotrophic lateral
      sclerosis (ALS), and expression of VEGFR2 is reduced in motor neurones and spinal
      cord of patients with ALS. METHODS: We have screened the promoter region and 4
      exonic regions of functional significance of the VEGFR2 gene in a UK population
      of patients with ALS, for mutations and polymorphisms that may affect expression
      or function of this VEGF receptor. RESULTS: No mutations were identified in the
      VEGFR2 gene. We found no association between polymorphisms in the regulatory
      regions of the VEGFR2 gene and ALS. CONCLUSION: Mechanisms other than genetic
      variation may downregulate expression or function of the VEGFR2 receptor in
      patients with ALS.

PMID- 17456230
TI  - Knowledge about safe motherhood and HIV/AIDS among school pupils in a rural area
      in Tanzania.
AB  - BACKGROUND: The majority of adolescents in Africa experience pregnancy,
      childbirth and enter motherhood without adequate information about maternal
      health issues. Information about these issues could help them reduce their
      pregnancy related health risks. Existing studies have concentrated on
      adolescents' knowledge of other areas of reproductive health, but little is known
      about their awareness and knowledge of safe motherhood issues. We sought to
      bridge this gap by assessing the knowledge of school pupils regarding safe
      motherhood in Mtwara Region, Tanzania. METHODS: We used qualitative and
      quantitative descriptive methods to assess school pupils' knowledge of safe
      motherhood and HIV/AIDS in pregnancy. An anonymous questionnaire was used to
      assess the knowledge of 135 pupils ranging in age from 9 to 17 years. The pupils
      were randomly selected from 3 primary schools. Underlying beliefs and attitudes
      were assessed through focus group interviews with 35 school children. Key
      informant interviews were conducted with six school teachers, two community
      leaders, and two health staffs. RESULTS: Knowledge about safe motherhood and
      other related aspects was generally low. While 67% of pupils could not mention
      the age at which a girl may be able to conceive, 80% reported it is safe for a
      girl to be married before she reaches 18 years. Strikingly, many school pupils
      believed that complications during pregnancy and childbirth are due to non
      observance of traditions and taboos during pregnancy. Birth preparedness,
      important risk factors, danger signs, postpartum care and vertical transmission
      of HIV/AIDS and its prevention measures were almost unknown to the pupils.
      CONCLUSION: Poor knowledge of safe motherhood issues among school pupils in rural
      Tanzania is related to lack of effective and coordinated interventions to address
      reproductive health and motherhood. For long-term and sustained impact, school
      children must be provided with appropriate safe motherhood information as early
      as possible through innovative school-based interventions.

PMID- 17456232
TI  - Inter- and intraspecific genetic and morphological variation in a sibling pair of
      carabid species.
AB  - BACKGROUND: Pogonus littoralis and Pogonus chalceus are very close related
      species with quite different ecological preferences within salt marshes. We study
      the evolutionary processes in and between these presumably young species.
      Therefore, we compare the variation in ecologically relevant characters and the
      genetic variation within one of the species (intraspecific differentiation) with
      the variation of the two types of characters between the two species
      (interspecific variation). Data are compared between two independent sets of
      populations, one set at a small geographical scale (the ecologically diverse
      Guerande area in France) and the other set at a Atlantic-Mediterranean scale.
      RESULTS: Body and relative wing size and IDH1 allozyme data show that the
      intraspecific variation in P. chalceus is high and in the same range as the
      interspecific variation (P. chalceus versus P. littoralis). Based on neutral
      markers (other allozymes and mitochondrial DNA) on the other hand, the
      intraspecific variation in P. chalceus is much lower in comparison to the
      interspecific variation. CONCLUSION: The different ecotypes in the highly
      polytypic species P. chalceus are as highly differentiated in ecological
      characters as true species, but are not recognised as such by screening neutral
      DNA polymorphisms. This can be interpreted as a case of ongoing speciation driven
      by natural selection adapting each ecotype to its respective ecological niche.
      The same ecological process can be recognised in the differentiation between the
      two sister species, where en plus reproductive isolation between the two gene
      pools occurred, allowing independent drift and mutation accumulation in neutral
      genetic characters.

PMID- 17456231
TI  - An exploratory study of community factors relevant for participatory malaria
      control on Rusinga Island, western Kenya.
AB  - BACKGROUND: Capacity strengthening of rural communities, and the various actors
      that support them, is needed to enable them to lead their own malaria control
      programmes. Here the existing capacity of a rural community in western Kenya was
      evaluated in preparation for a larger intervention. METHODS: Focus group
      discussions and semi-structured individual interviews were carried out in 1,451
      households to determine (1) demographics of respondent and household; (2) socio
      economic status of the household; (3) knowledge and beliefs about malaria
      (symptoms, prevention methods, mosquito life cycle); (4) typical practices used
      for malaria prevention; (5) the treatment-seeking behaviour and household
      expenditure for malaria treatment; and (6) the willingness to prepare and
      implement community-based vector control. RESULTS: Malaria was considered a major
      threat to life but relevant knowledge was a chimera of scientific knowledge and
      traditional beliefs, which combined with socio-economic circumstances, leads to
      ineffective malaria prevention. The actual malaria prevention behaviour practiced
      by community members differed significantly from methods known to the
      respondents. Beside bednet use, the major interventions implemented were bush
      clearing and various hygienic measures, even though these are ineffective for
      malaria prevention. Encouragingly, most respondents believed malaria could be
      controlled and were willing to contribute to a community-based malaria control
      program but felt they needed outside assistance. CONCLUSION: Culturally sensitive
      but evidence-based education interventions, utilizing participatory tools, are
      urgently required which consider traditional beliefs and enable understanding of
      causal connections between mosquito ecology, parasite transmission and the
      diagnosis, treatment and prevention of disease. Community-based organizations and
      schools need to be equipped with knowledge through partnerships with national and
      international research and tertiary education institutions so that evidence-based
      research can be applied at the grassroots level.

PMID- 17456233
TI  - IFNG +874T/A polymorphism is not associated with American tegumentary
      leishmaniasis susceptibility but can influence Leishmania induced IFN-gamma
      production.
AB  - BACKGROUND: Interferon-gamma is a key cytokine in the protective responses
      against intracellular pathogens. A single nucleotide polymorphism (SNP) located
      in the first intron of the human IFN-gamma gene can putatively influence the
      secretion of cytokine with an impact on infection outcome as demonstrated for
      tuberculosis and other complex diseases. Our aim was to investigate the putative
      association of IFNG+874T/A SNP with American tegumentary leishmaniasis (ATL) and
      also the influence of this SNP in the secretion of IFN-gamma in vitro. METHODS:
      Brazilian ATL patients (78 cutaneous, CL, and 58 mucosal leishmaniasis, ML) and
      609 healthy volunteers were evaluated. The genotype of +874 region in the IFN
      gamma gene was carried out by Amplification Refractory Mutational System (ARMS
      PCR). Leishmania-induced IFN-gamma production on peripheral blood mononuclear
      cell (PBMC) culture supernatants was assessed by ELISA. RESULTS: There are no
      differences between +874T/A SNP frequency in cases and controls or in ML versus
      CL patients. Cutaneous leishmaniasis cases exhibiting AA genotype produced lower
      levels of IFN-gamma than TA/TT genotypes. In mucosal cases, high and low IFN
      gamma producers were clearly demonstrated but no differences in the cytokine
      production was observed among the IFNG +874T or A carriers. CONCLUSION: Our
      results suggest that +874T/A polymorphism was not associated with either
      susceptibility or severity to leishmaniasis. Despite this, IFNG +874T/A SNP could
      be involved in the pathogenesis of leishmaniasis by influencing the amount of
      cytokine released by CL patients, although it could not prevent disease
      development. On the other hand, it is possible that in ML cases, other potential
      polymorphic regulatory genes such as TNF-alpha and IL-10 are also involved thus
      interfering with IFN-gamma secretion.

PMID- 17456234
TI  - Papanicolaou smears and cervical inflammatory cytokine responses.
AB  - In a case-control study among 2064 South African women to investigate the risk of
      clinically invasive cancer of the cervix, we found a marked reduction in the risk
      of cervical cancer among women who gave a history of ever having undergone even a
      single Pap smear, and a statistically significant decline in the HPV positivity
      rate correlated with the lifetime number of Pap smears received. HPV infections
      and their associated low-grade lesions commonly regress, indicating that most
      often there is an effective host immune response against HPV infection. We
      hypothesized that act of performing a Pap smear is associated with inflammatory
      responses at the site of trauma, the cervix, and that this inflammatory
      signalling may be an immunological factor initiating these productive anti-HPV
      responses. In the present study, a randomized controlled trial, we enrolled 80
      healthy young women to investigate the impact of performing a Pap smear on
      cervical inflammation. Forty one women, in the intervention group, received a Pap
      smear at enrollment and cervicovaginal lavages (CVLs) were collected at baseline
      and 2 weeks later. Thirty nine women received no intervention at enrollment
      (control group) but CVLs were collected at enrolment and 2 weeks later. We
      assessed various markers of inflammation including IL-12 p70, TNF-alpha, IL-8, IL
      6, IL-10, and IL-1beta in CVL specimens. While CVL levels of IL-8, IL-1beta and
      IL-6 remained unchanged following a Pap smear, markers of cell mediated immunity
      (IL-12 p70 and TNF-alpha) and T cell regulation (IL-10) were significantly
      elevated.

PMID- 17456236
TI  - Assessment and prevention of acute health effects of weather conditions in
      Europe, the PHEWE project: background, objectives, design.
AB  - BACKGROUND: The project "Assessment and prevention of acute health effects of
      weather conditions in Europe" (PHEWE) had the aim of assessing the association
      between weather conditions and acute health effects, during both warm and cold
      seasons in 16 European cities with widely differing climatic conditions and to
      provide information for public health policies. METHODS: The PHEWE project was a
      three-year pan-European collaboration between epidemiologists, meteorologists and
      experts in public health. Meteorological, air pollution and mortality data from
      16 cities and hospital admission data from 12 cities were available from 1990 to
      2000. The short-term effect on mortality/morbidity was evaluated through city
      specific and pooled time series analysis. The interaction between weather and air
      pollutants was evaluated and health impact assessments were performed to quantify
      the effect on the different populations. A heat/health watch warning system to
      predict oppressive weather conditions and alert the population was developed in a
      subgroup of cities and information on existing prevention policies and of
      adaptive strategies was gathered. RESULTS: Main results were presented in a
      symposium at the conference of the International Society of Environmental
      Epidemiology in Paris on September 6th 2006 and will be published as scientific
      articles. The present article introduces the project and includes a description
      of the database and the framework of the applied methodology. CONCLUSION: The
      PHEWE project offers the opportunity to investigate the relationship between
      temperature and mortality in 16 European cities, representing a wide range of
      climatic, socio-demographic and cultural characteristics; the use of a
      standardized methodology allows for direct comparison between cities.

PMID- 17456235
TI  - Malignant hyperthermia.
AB  - Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that
      presents as a hypermetabolic response to potent volatile anesthetic gases such as
      halothane, sevoflurane, desflurane and the depolarizing muscle relaxant
      succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and
      heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000-100,000
      anesthesias. However, the prevalence of the genetic abnormalities may be as great
      as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses,
      and probably other animals. The classic signs of MH include hyperthermia to
      marked degree, tachycardia, tachypnea, increased carbon dioxide production,
      increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all
      related to a hypermetabolic response. The syndrome is likely to be fatal if
      untreated. Early recognition of the signs of MH, specifically elevation of end
      expired carbon dioxide, provides the clinical diagnostic clues. In humans the
      syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal
      recessive. The pathophysiologic changes of MH are due to uncontrolled rise of
      myoplasmic calcium, which activates biochemical processes related to muscle
      activation. Due to ATP depletion, the muscle membrane integrity is compromised
      leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused
      by a defect in the ryanodine receptor. Over 90 mutations have been identified in
      the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH.
      Diagnostic testing relies on assessing the in vitro contracture response of
      biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the
      genetic changes has led to the introduction, on a limited basis so far, of
      genetic testing for susceptibility to MH. As the sensitivity of genetic testing
      increases, molecular genetics will be used for identifying those at risk with
      greater frequency. Dantrolene sodium is a specific antagonist of the
      pathophysiologic changes of MH and should be available wherever general
      anesthesia is administered. Thanks to the dramatic progress in understanding the
      clinical manifestation and pathophysiology of the syndrome, the mortality from MH
      has dropped from over 80% thirty years ago to less than 5%.

PMID- 17456237
TI  - Consultative meeting to develop a strategy for treatment of cutaneous
      leishmaniasis. Institute Pasteur, Paris. 13-15 June, 2006.
AB  - BACKGROUND: A meeting was organized by Drugs for Neglected Diseases initiative
      (DNDi) and the Institute Pasteur (IP), Paris, to review the treatment for all
      forms of cutaneous leishmaniasis (CL) and to propose a strategy for the
      development of new efficacious and affordable treatments. METHOD: The global
      burden of CL was discussed with respect to financial impact; relation to poverty;
      the stigma of CL lesions and scars (particularly in young women); lack of
      effective, affordable, easily implemented tools and political will and resources
      to implement available control tools; and lack of input from pharmaceutical and
      biotechnology companies to develop new drugs and vaccines. RESULTS: According to
      the experts from different endemic countries present, the financial and social
      burdens of CL are high, but we have limited quantitative data. The analysis of
      published trials indicates that the quality of most trials is poor and requires
      both improvement and standardization. The available drugs are inadequate.
      Criteria by which different CL types could be prioritized as target disease were
      set. These criteria included: severity of the disease; lack of response to
      available drugs; overall incidence and prevalence of the disease; sequelae of the
      disease, (including recidivans and mucosal leishmaniasis); the impact of
      treatment of individuals on control of transmission and lack of other major
      parties involved in drug development. Based on these, the anthroponotic CL and
      its sequel "recidivans" caused by L. tropica and CL caused by L. braziliensis and
      its sequel, mucosal leishmaniasis were considered to be the target diseases. The
      mechanism for controlling Leishmania infection to reach a stable self healing
      process is a balanced immune response. Immune stimulation during chemotherapy can
      enhance cure. There is no adequately effective vaccine, but some encouraging
      results have been obtained with whole killed Leishmania parasites or imiquimod
      (an immuno-modulator) plus antimonials. Further studies are needed. One
      safety/immunogenicity clinical trial is currently ongoing with a Second
      Generation Vaccine (SGV). CONCLUSIONS AND RECOMMENDATIONS: There is an urgent
      need for new treatments for all CL types. CL should be considered as a neglected
      disease and organizations, such as DNDi, should include it in their list of
      target diseases. It was agreed that immuno-chemotherapy (with "therapeutic"
      vaccines or immunomodulators) has a strong potential to make an impact as a new
      therapy of CL with the view of shortening/reducing duration and dose of drug
      treatment and preventing resistance. There is also a need for safe, affordable
      and efficacious new chemotherapeutics. The quality of clinical trials needs to be
      enhanced and standardized. Short and long-term objectives and activities were
      defined as a part of meeting recommendations.

PMID- 17456238
TI  - Multiple non-collinear TF-map alignments of promoter regions.
AB  - BACKGROUND: The analysis of the promoter sequence of genes with similar
      expression patterns is a basic tool to annotate common regulatory elements.
      Multiple sequence alignments are on the basis of most comparative approaches. The
      characterization of regulatory regions from co-expressed genes at the sequence
      level, however, does not yield satisfactory results in many occasions as promoter
      regions of genes sharing similar expression programs often do not show nucleotide
      sequence conservation. RESULTS: In a recent approach to circumvent this
      limitation, we proposed to align the maps of predicted transcription factors
      (referred as TF-maps) instead of the nucleotide sequence of two related
      promoters, taking into account the label of the corresponding factor and the
      position in the primary sequence. We have now extended the basic algorithm to
      permit multiple promoter comparisons using the progressive alignment paradigm. In
      addition, non-collinear conservation blocks might now be identified in the
      resulting alignments. We have optimized the parameters of the algorithm in a
      small, but well-characterized collection of human-mouse-chicken-zebrafish
      orthologous gene promoters. CONCLUSION: Results in this dataset indicate that TF
      map alignments are able to detect high-level regulatory conservation at the
      promoter and the 3'UTR gene regions, which cannot be detected by the typical
      sequence alignments. Three particular examples are introduced here to illustrate
      the power of the multiple TF-map alignments to characterize conserved regulatory
      elements in absence of sequence similarity. We consider this kind of approach can
      be extremely useful in the future to annotate potential transcription factor
      binding sites on sets of co-regulated genes from high-throughput expression
      experiments.

PMID- 17456239
TI  - Discovery of tissue-specific exons using comprehensive human exon microarrays.
AB  - BACKGROUND: Higher eukaryotes express a diverse population of messenger RNAs
      generated by alternative splicing. Large-scale methods for monitoring gene
      expression must adapt in order to accurately detect the transcript variation
      generated by this splicing. RESULTS: We have designed a high-density
      oligonucleotide microarray with probesets for more than one million annotated and
      predicted exons in the human genome. Using these arrays and a simple algorithm
      that normalizes exon signal to signal from the gene as a whole, we have
      identified tissue-specific exons from a panel of 16 different normal adult
      tissues. RT-PCR validation confirms approximately 86% of the predicted tissue
      enriched probesets. Pair-wise comparisons between the tissues suggest that as
      many as 73% of detected genes are differentially alternatively spliced. We also
      demonstrate how an inclusive exon microarray can be used to discover novel
      alternative splicing events. As examples, 17 new tissue-specific exons from 11
      genes were validated by RT-PCR and sequencing. CONCLUSION: In conjunction with a
      conceptually simple algorithm, comprehensive exon microarrays can detect tissue
      specific alternative splicing events. Our data suggest significant expression
      outside of known exons and well annotated genes and a high frequency of
      alternative splicing events. In addition, we identified and validated a number of
      novel exons with tissue-specific splicing patterns. The tissue map data will
      likely serve as a valuable source of information on the regulation of alternative
      splicing.

PMID- 17456240
TI  - Interventionally implanted port catheter systems for hepatic arterial infusion of
      chemotherapy in patients with colorectal liver metastases: a Phase II-study and
      historical comparison with the surgical approach.
AB  - BACKGROUND: The high complication rates of surgically implanted port catheter
      systems (SIPCS) represents a major drawback in the treatment of isolated liver
      neoplasms by hepatic arterial infusion (HAI) of chemotherapy. Interventionally
      implanted port catheter systems (IIPCS) have evolved into a promising alternative
      that enable initiation of HAI without laparatomy, but prospective data on this
      approach are still sparse. Aim of this study was to evaluate the most important
      technical endpoints associated with the use of IIPCS for the delivery of 5
      fluorouracil-based HAI in patients with colorectal liver metastases in a phase 2
      study, and to perform a non-randomised comparison with a historical group of
      patients in which HAI was administered via SIPCS. METHODS: 41 patients with
      isolated liver metastases of colorectal cancer were enrolled into a phase II
      study and provided with IIPCS between 2001 and 2004 (group A). The primary
      objective of the trial was defined as evaluation of device-related complications
      and port duration. Results were compared with those observed in a pre-defined
      historical collective of 40 patients treated with HAI via SIPCS at our
      institution between 1996 and 2000 (group B). RESULTS: Baseline characteristics
      were balanced between both groups, except for higher proportions of previous
      palliative pre-treatment and elevated serum alkaline phosphatase in patients of
      group A. Implantation of port catheters was successful in all patients of group
      A, whereas two primary failures were observed in group B. The frequency of device
      related complications was similar between both groups, but the secondary failure
      rate was significantly higher with the use of surgical approach (17% vs. 50%, p <
      0.01). Mean port duration was significantly longer in the interventional group
      (19 vs. 14 months, p = 0.01), with 77 vs. 50% of devices functioning at 12 months
      (p < 0.01). No unexpected complications were observed in both groups. CONCLUSION:
      HAI via interventionally implanted port catheters can be safely provided to a
      collective of patients with colorectal liver metastases, including a relevant
      proportion of preatreated individuals. It appears to offer technical advantages
      over the surgical approach.

PMID- 17456241
TI  - Practice development plans to improve the primary care management of acute
      asthma: randomised controlled trial.
AB  - BACKGROUND: Our professional development plan aimed to improve the primary care
      management of acute asthma, which is known to be suboptimal. METHODS: We invited
      59 general practices in Grampian, Scotland to participate. Consenting practices
      were randomised to early and delayed intervention groups. Practices undertook
      audits of their management of all acute attacks (excluding children under 5
      years) occurring in the 3 months preceding baseline, 6-months and 12-months study
      time-points. The educational programme [including feedback of audit results,
      attendance at a multidisciplinary interactive workshop, and formulation of
      development plan by practice teams] was delivered to the early group at baseline
      and to the delayed group at 6 months. Primary outcome measure was recording of
      peak flow compared to best/predicted at 6 months. Analyses are presented both
      with, and without adjustment for clustering. RESULTS: 23 consenting practices
      were randomised: 11 to early intervention. Baseline practice demography was
      similar. Six early intervention practices withdraw before completing the baseline
      audit. There was no significant improvement in our primary outcome measure (the
      proportion with peak flow compared to best/predicted) at either the 6 or 12 month
      time points after adjustment for baseline and practice effects. However, the
      between group difference in the adjusted combined assessment score, whilst non
      significant at 6 months (Early: 2.48 (SE 0.43) vs. Delayed 2.26 (SE 0.33) p =
      0.69) reached significance at 12 m (Early:3.60 (SE 0.35) vs. Delayed 2.30 (SE
      0.28) p = 0.02). CONCLUSION: We demonstrated no significant benefit at the a
      priori 6-month assessment point, though improvement in the objective assessment
      of attacks was shown after 12 months. Our practice development programme,
      incorporating audit, feedback and a workshop, successfully engaged the healthcare
      team of participating practices, though future randomised trials of educational
      interventions need to recognise that effecting change in primary care practices
      takes time. Monitoring of the assessment of acute attacks proved to be a feasible
      and responsive indicator of quality care.

PMID- 17456243
TI  - A descriptive study of mastitis in Australian breastfeeding women: incidence and
      determinants.
AB  - BACKGROUND: Mastitis is one of the most common problems experienced by women who
      are breastfeeding. Mastitis is an inflammation of breast tissue, which may or may
      not result from infection. The aims of this paper are to compare rates of
      mastitis in primiparous women receiving public hospital care (standard or birth
      centre) and care in a co-located private hospital, and to use multivariate
      analysis to explore other factors related to mastitis. METHODS: Data from two
      studies (a randomised controlled trial [RCT] and a survey) have been combined.
      The RCT (Attachment to the Breast and Family Attitudes to Breastfeeding, ABFAB)
      which was designed to test whether breastfeeding education in mid-pregnancy could
      increase breastfeeding duration recruited public patients at the Royal Women's
      Hospital at 18-20 weeks gestation. A concurrent survey recruited women planning
      to give birth in the Family Birth Centre (at 36 weeks gestation) and women in the
      postnatal wards of Frances Perry House (private hospital). All women were
      followed up by telephone at 6 months postpartum. Mastitis was defined as at least
      2 breast symptoms (pain, redness or lump) AND at least one of fever or flu-like
      symptoms. RESULTS: The 6 month telephone interview was completed by 1193 women.
      Breastfeeding rates at 6 months were 77% in Family Birth Centre, 63% in Frances
      Perry House and 53% in ABFAB. Seventeen percent (n = 206) of women experienced
      mastitis. Family Birth Centre and Frances Perry House women were more likely to
      develop mastitis (23% and 24%) than women in ABFAB (15%); adjusted odds ratio
      (Adj OR) ~1.9. Most episodes occurred in the first 4 weeks postpartum: 53%
      (194/365). Nipple damage was also associated with mastitis (Adj OR 1.7, 95% CI,
      1.14, 2.56). We found no association between breastfeeding duration and mastitis.
      CONCLUSION: The prevention and improved management of nipple damage could
      potentially reduce the risk of lactating women developing mastitis. TRIAL
      REGISTRATION: Trial registration (ABFAB): Current Controlled Trials
      ISRCTN21556494.

PMID- 17456242
TI  - Gene expression patterns during adaptation of a helminth parasite to different
      environmental niches.
AB  - BACKGROUND: Schistosome bloodflukes are complex trematodes responsible for 200
      million cases of schistosomiasis worldwide. Their life cycle is characterized by
      a series of remarkable morphological and biochemical transitions between an
      invertebrate host, an aquatic environment, and a mammalian host. We report a
      global transcriptional analysis of how this parasite alters gene regulation to
      adapt to three distinct environments. RESULTS: Utilizing a genomic microarray
      made of 12,000 45-50-mer oligonucleotides based on expressed sequence tags, three
      different developmental stages of the schistosome parasite were analyzed by pair
      wise comparisons of transcript hybridization signals. This analysis resulted in
      the identification of 1,154 developmentally enriched transcripts. CONCLUSION:
      This study expands the repertoire of schistosome genes analyzed for stage
      specific expression to over 70% of the predicted genome. Among the new
      associations identified are the roles of robust protein synthesis and programmed
      cell death in development of cercariae in the sporocyst stages, the relative
      paucity of cercarial gene expression outside of energy production, and the
      remarkable diversity of adult gene expression programs that reflect adaptation to
      the host bloodstream and an average lifespan that may approach 10 years.

PMID- 17456245
TI  - The potential effect of iron defortification on iron-deficiency anaemia in the US
      population.
AB  - OBJECTIVE: To quantify the potential effect of iron defortification in the USA on
      iron-deficiency anaemia (IDA). METHODS: Monte Carlo models were built to simulate
      iron nutrition in the US population. A hypothetical cohort of 15 000 persons from
      the general population was used in 15-year simulations to compare the prevalence
      of IDA with and without fortification. RESULTS: With iron fortification, the
      prevalence of IDA was 2.4% for children aged 3-5 years, 5.4% for women aged 20-49
      years, and 0.14% for men aged 20-49 years. The corresponding IDA estimates under
      iron defortification were 4.5%, 8.2% and 0.46%, respectively. Defortification had
      little effect on the distribution of iron indicators at or above the 50th
      percentile within each of these three groups and little effect on the
      distributions of iron indicators among adult men. CONCLUSION: Iron
      defortification is likely to increase IDA among children and women of
      reproductive age, but is not likely to have meaningful effects on the iron status
      of men or the majority of women and children.

PMID- 17456244
TI  - Amelioration of galactosamine-induced nephrotoxicity by a protein isolated from
      the leaves of the herb, Cajanus indicus L.
AB  - BACKGROUND: Galactosamine (GalN), an established experimental toxin, mainly
      causes liver injury via the generation of free radicals and depletion of UTP
      nucleotides. Renal failure is often associated with end stage liver damage. GalN
      intoxication also induces renal dysfunction in connection with hepatic disorders.
      Present study was designed to find out the effect of a protein isolated from the
      leaves of the herb Cajanus indicus against GalN induced renal damage. METHODS:
      Both preventive as well as curative effect of the protein was investigated in the
      study. GalN was administered intraperitoneally at a dose of 800 mg/kg body weight
      for 3 days pre and post to protein treatment at an intraperitoneal dose of 2
      mg/kg body weight for 4 days. The activities of antioxidant enzymes, superoxide
      dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione-S
      transferase (GST), levels of cellular metabolites, reduced glutathione (GSH),
      total thiols, oxidized glutathione (GSSG) and lipid peroxidation end products
      were determined to estimate the status of the antioxidative defense system. In
      addition, serum creatinine and urea nitrogen (UN) levels were also measured as a
      marker of nephrotoxicity. RESULTS: Results showed that GalN treatment
      significantly increased the serum creatinine and UN levels compared to the normal
      group of mice. The extent of lipid peroxidation and the level of GSSG were also
      enhanced by the GalN intoxication whereas the activities of antioxidant enzymes
      SOD, CAT, GR and GST as well as the levels of total thiols and GSH were decreased
      in the kidney tissue homogenates. Protein treatment both prior and post to the
      toxin administration successfully altered the effects in the experimental mice.
      CONCLUSION: Our study revealed that GalN caused a severe oxidative insult in the
      kidney. Protein treatment both pre and post to the GalN intoxication could
      protect the kidney tissue against GalN induced oxidative stress. As GalN induced
      severe hepatotoxicity followed by renal failure, the protective role of the
      protein against GalN induced renal damages is likely to be an indirect effect.
      Since the protein possess hepatoprotective activity, it may first ameliorate GalN
      induced liver damage and consequently the renal disorders are reduced. To the
      best of our knowledge, this is probably the first report describing GalN-induced
      oxidative stress in renal damages and the protective role of a plant protein
      molecule against it.

PMID- 17456246
TI  - Relationship of glycaemic index with cardiovascular risk factors: analysis of the
      National Diet and Nutrition Survey for people aged 65 and older.
AB  - OBJECTIVE: To identify associations between dietary glycaemic index (GI) and
      weight, body mass index and other risk factors for cardiovascular disease (CVD) -
      waist-to-hip ratio (WHR), lipoprotein fractions, triacylglycerols (TAG) and blood
      pressure (BP) - in an older British population. DESIGN: Cross-sectional dietary,
      anthropometric and biochemical data from the National Diet and Nutritional Survey
      for adults aged over 65 years were reanalysed using a hierarchical regression
      model. Associations between body weight, CVD risk factors, and dietary factors
      including GI and fibre intakes were explored among 1152 healthy older people
      living in the UK between 1994 and 1995. RESULTS: In the unadjusted model, GI was
      significantly and directly associated with TAG (beta = 0.008 +/- 0.003) and
      diastolic BP (beta = 0.325 +/- 0.164) in males. These relationships were
      attenuated and non-significant after adjustment for potential confounding
      factors. WHR (beta = 0.003 +/- 0.001) and TAG (beta = 0.005 +/- 0.002) were
      significantly predicted by GI in males and females combined. The association with
      WHR was attenuated by adjustment for sex, age, region and social class; the
      relationship with TAG was non-significant after adjustment for other potential
      dietary confounders. CONCLUSION: After controlling for potential confounders, no
      clear links were detected between GI and body weight or other CVD risk factors.
      This study provides little evidence for advising the consumption of a low-GI diet
      in the elderly to prevent weight gain or improve other CVD risk factors.

PMID- 17456247
TI  - Family planning in rural Adana, Turkey.
AB  - This study of family planning in rural Adana, Turkey, collected data from 519
      women aged between 16 and 55. Questionnaires were distributed in different
      districts during February 2006. Ths results showed that 81.3% of women used a
      contraceptive method. The IUD was the most widely used modern contraceptive
      method. There is a decrease in the average number of births per woman as the
      educational level of women increases.

PMID- 17456248
TI  - A randomised comparison of increase in serum 25-hydroxyvitamin D concentration
      after 4 weeks of daily oral intake of 10 microg cholecalciferol from multivitamin
      tablets or fish oil capsules in healthy young adults.
AB  - Many types of vitamin supplements are available on the market, but little is
      known about whether cholecalciferol obtained from fat-containing capsules differs
      in bioavailability from that of solid tablets. Our objective was to test whether
      4 weeks of daily supplementation with 10 mug cholecalciferol given as a fish oil
      capsule produces a larger increase in serum 25-hydroxyvitamin D (s-25(OH)D)
      concentration compared with the same dose of cholecalciferol given as a
      multivitamin tablet. A total of seventy-four healthy subjects aged 19-49 years
      were initially included and fifty-five of these completed the study and fulfilled
      the inclusion criteria. After completing a self-administered questionnaire about
      diet and sunshine exposure and having a non-fasting venous blood sample drawn,
      participants were randomised to receive daily multivitamin tablets (n 28) or fish
      oil capsules (n 27), each containing equal doses of cholecalciferol. A second
      blood sample was drawn after 28 d. Mean baseline s-25(OH)D was 40.3 (sd 22.0)
      nmol/l in the multivitamin group and 48.5 (24.8) nmol/l in the fish oil group.
      When controlling for baseline s-25(OH)D, mean 4-week increase in s-25(OH)D was
      35.8 (95 % CI 30.9, 40.8) nmol/l in the multivitamin group and 32.3 (95 % CI
      27.3, 37.4) nmol/l in the fish oil group; the mean difference was 3.5 (95 % CI -
      3.6, 10.6) nmol/l (P = 0.33). The results were unaltered by statistical
      adjustment for BMI, ethnic background, age and sex. We conclude that fish oil
      capsules and multivitamin tablets containing 10 microg cholecalciferol
      administered over a 4-week period produced a similar mean increase in s-25(OH)D
      concentration.

PMID- 17456249
TI  - Effect of excessive iodine exposure on the placental deiodinase activities and
      Hoxc8 expression during mouse embryogenesis.
AB  - Excessive iodine induces thyroid dysfunction. However, the effect of excessive
      iodine exposure on maternal-fetal thyroid hormone metabolism and on the
      expression of genes involved in differentiation, growth and development is poorly
      understood. Since a thyroid hormone receptor response element was found in the
      Hoxc8 promoter region, Hoxc8 expression possibly regulated by excessive iodine
      exposure was firstly investigated. In the present study, Balb/C mice were given
      different doses of iodine in the form of potassium iodate (KIO3) at the levels of
      0 (sterile water), 1.5, 3.0, 6.0, 12.0 and 24.0 microg/ml in drinking water for 4
      months, then were mated. On 12.5 d postcoitum, placental type 2 and type 3
      deiodinase activities and fetal Hoxc8 expression were determined. The results
      showed that excessive iodine exposure above 1.5 microg/ml resulted in an increase
      of total thyroxine and a decrease of total triiodothyronine in the serum of
      maternal mice, which was mainly associated with the inhibition of type 1
      deiodinase activity in liver and kidney. Placental type 2 deiodinase activity
      decreased, showing an inverse relationship with maternal thyroxine level. Hoxc8
      mRNA and protein expression at 12.5 d postcoitum embryos were down regulated.
      Because Hoxc8 plays an important role in normal skeletal development, this
      finding provides a possible explanation for the skeletal malformation induced by
      excessive iodine exposure and also provides a new clue to study the relationship
      between iodine or thyroid hormones and Hox gene expression pattern.

PMID- 17456252
TI  - Remote detection of volatile organic compounds by passive multispectral infrared
      imaging measurements.
AB  - Automated pattern recognition methodology is described for the detection of
      signatures of volatile organic compounds from passive multispectral infrared
      imaging data collected from an aircraft platform. Data are acquired in an across
      track scanning mode with a downward-looking line scanner based on 8 to 16
      spectral channels in the 8-14 and 3-5 microm spectral ranges. Two controlled
      release experiments are performed in which plumes of ethanol are generated and
      detected from aircraft overflights at altitudes of 2200 to 2800 ft (671 to 853
      m). In addition, a methanol release from a chemical manufacturing facility is
      monitored. Automated classifiers are developed by application of piecewise linear
      discriminant analysis to the calibrated, registered, and preprocessed radiance
      data acquired by the line scanner. Preprocessing steps evaluated include contrast
      enhancement, temperature-emissivity separation, feature selection, and feature
      extraction/noise reduction by the minimum noise fraction (MNF) transform.
      Successful classifiers are developed for both compounds and are tested with data
      not used in the classifier development. Separation of temperature and emissivity
      by use of the alpha residual calculation is found to reduce false positive
      detections to a negligible level, and the MNF transform is shown to enhance
      detection sensitivity.

PMID- 17456253
TI  - On-line characterization of YBCO coated conductors using Raman spectroscopy
      methods.
AB  - The use of Raman spectroscopy for on-line monitoring of the production of
      superconducting YBa2Cu3O6+X (YBCO) thin films on long-length metal tapes coated
      with textured buffer layers is reported for the first time. A methodology is
      described for obtaining Raman spectra of YBCO on moving tape exiting a metal
      organic-chemical-vapor-deposition (MOCVD) enclosure. After baseline correction,
      the spectra recorded in this way show the expected phonons of the specific YBCO
      crystal orientation required for high supercurrent transport, as well as phonons
      of non-superconducting second-phase impurities when present. It is also possible
      to distinguish YBCO films that are properly textured from films having domains of
      misoriented YBCO grains. An investigation of the need for focus control on moving
      tape indicated that focusing of the laser on the surface of the highly reflective
      YBCO films exiting the MOCVD enclosure tends to produce aberrant photon bursts
      that swamp the Raman spectrum. These photon bursts are very likely a consequence
      of optical speckle effects induced by a combination of surface roughness,
      crystallographic texture, and/or local strain within the small grain
      microstructure of the YBCO film. Maintaining a slightly out-of-focus condition
      provides the best signal-to-noise ratio in terms of the obtained Raman spectra.
      In addition to examining moving tape at the post-MOCVD stage, Raman spectra of
      the film surface can also be recorded after the oxygen anneal performed to bring
      the YBCO to the optimum superconducting state. Consideration is given to data
      processing methods that could be adapted to the on-line Raman spectra to allow
      the tagging of out-of-specification tape segments and, at a more advanced level,
      feedback control to the MOCVD process.

PMID- 17456254
TI  - Diffusion measurements in binary liquid mixtures by Raman spectroscopy.
AB  - It is shown that Raman spectroscopy allows determination of the molar fractions
      in mixtures subjected to molecular diffusion. Spectra of three binary systems,
      benzene/n-hexane, benzene/cyclohexane, and benzene/acetone, were obtained during
      vertical (exchange) diffusion at several different heights (z) as a function of
      time. A procedure to determine time-dependent concentration profiles and
      diffusion coefficients is described in detail for one system, and results are
      given for the two other cases. For the system benzene/cyclohexane, much lower
      diffusion coefficients than reported in the literature were found, even in a
      thermostatically controlled diffusion cell, recording spectra through circulating
      water. For the system benzene/acetone, the determined diffusion coefficients were
      in good agreement with the literature data. The limitations of the Raman method
      are discussed, and it is concluded that many more systems ought to be studied. It
      is pointed out that diffusion profiles can be obtained in ternary and higher
      systems, where proper measurements are almost nonexistent.

PMID- 17456255
TI  - From curdlan powder to the triple helix gel structure: an attenuated total
      reflection-infrared study of the gelation process.
AB  - Infrared spectroscopy was used to probe the hydration and gelation of curdlan, a
      linear polysaccharide built from repeating units of (1-->3)-beta-D-glucose. The
      spectra have been recorded using a temperature-controlled attenuated total
      reflection (ATR) device. Thermal gelation of curdlan could therefore be followed
      in situ and in real time. The transformation of the low-set gel, mainly formed
      with single helices, into a high-set gel, associated with a triple helix
      structure, could be directly observed. The relative intensities and positions of
      characteristic absorption bands in the C-O region (1200-850 cm-1) were found to
      be representative of the gel structure, as they are believed to be sensitive to
      the helical conformation of the polymer chains. Infrared (IR) spectroscopy is
      shown to be a useful tool for rapid and efficient characterization of curdlan
      gels.

PMID- 17456256
TI  - Using fourier transform infrared spectroscopy to examine structure in bisurea
      organogels.
AB  - The structure of two bisurea organogels was examined by Fourier-transform
      infrared (FT-IR) spectroscopy. Organogels were prepared in benzene at different
      concentrations of gelator in order to determine the effect of concentration on
      the assembly of organogelator molecules. This work examined two types of bisurea
      organogelators, both with dodecyl alkyl tail groups. The two molecules differ
      only in the length of an alkyl chain separating their two urea groups: 6 carbons
      in the C6C12 organogelator (1,6-bis(3(3,5-didodecoxybinzyl)-urea-hexane) and 12
      carbons in the C12C12 organogelator (1,12-bis(3(3,5-didodecoxybinzyl)-urea
      dodecane). The degree of urea hydrogen bonding was determined from the position
      of the amide II band, and the conformational order of the alkyl chains in the
      organogelator was determined in the methylene bending region. Both gels showed a
      general trend of less hydrogen bonding and greater conformational disorder in the
      alkyl chains as the concentration of organogelator increased; however, the
      changes were smaller in the C12C12 gels. This decrease in structural order with
      increasing organogelator concentration is explained by the kinetics of gel
      formation; more concentrated gels solidify too quickly to assemble perfectly. The
      observed differences between the two organogelators are caused by the different
      structures into which these two similar molecules assemble. The C6C12
      organogelator only assembles linearly, while the C12C12 organogelator can form
      sheets through brick-like packing, and these packing motifs were confirmed by
      scanning electron microscopy.

PMID- 17456257
TI  - Measurement of the absorption and scattering properties of turbid liquid foods
      using hyperspectral imaging.
AB  - A hyperspectral imaging system in line scanning mode was used for measuring the
      absorption and scattering properties of turbid food materials over the visible
      and near-infrared region of 530-900 nm. An instrumental calibration procedure was
      developed to compensate for the nonuniform instrument response of the imaging
      system. A nonlinear curve-fitting algorithm for a steady-state diffusion theory
      model was proposed to determine absorption (mua) and reduced scattering
      coefficients (mu's) from the spatially resolved hyperspectral reflectance
      profiles. The hyperspectral imaging system provided good measurement of mua and
      mu's for the simulation samples made of Intralipid scattering material and three
      absorbers (blue dye, green dye, and black ink) with average fitting errors of 16%
      and 11%, respectively. The optical properties of the fruit and vegetable juices
      and milks were determined. Values of the absorption and reduced scattering
      coefficient at 600 nm were highly correlated to the fat content of the milk
      samples with the correlation coefficient of 0.995 and 0.998, respectively.
      Compared to time-resolved and frequency-domain techniques, the hyperspectral
      imaging technique provides a faster and simpler means for measuring the optical
      properties of turbid food and agricultural products.

PMID- 17456258
TI  - Variations in predicted values from near-infrared spectra of samples in vials by
      using a calibration model developed from spectra of samples in vials: causes of
      the variations and compensation methods.
AB  - The causes and compensation methods of variations in the predicted values from
      near-infrared (NIR) spectra of samples in vials by using a calibration model
      developed from spectra of samples in vials were studied. From the viewpoint of
      the path length and the peak height of spectra in the NIR region, vials with 1 mL
      volume (external diameter: 8 mm, inside diameter: about 6 mm, length: 40 mm) were
      selected as disposable vials for the samples. To investigate the causes of the
      variations in the predicted values, the optical path lengths and transmittance
      spectra of empty vials in five lots produced during the last four years were
      examined. The results showed that there were some differences in the path lengths
      of the vials and in the intensities of peaks near 7130 and 4515 cm-1, which were
      attributed to the hydroxyl groups in the spectra of the vials among the five
      lots. The calibration models for the concentration of isopropyl alcohol (IPA) in
      toluene contained in vials of the same lot were developed. To search the
      pretreatment methods for the best calibration model with small variations in the
      predictive values of the samples in the vials, six kinds of pretreatments (no
      pretreatment, baseline correction, first derivative, second derivative,
      multiplicative scattering correction (MSC), and standard normal variate (SNV))
      were compared. The results indicated that MSC is a very effective method with
      small variation in the predicted values from the spectra of samples in vials. It
      was found that the variations in the predicted values are caused mainly by
      variations in the path lengths of vials. In real quality control, the NIR
      chemometrics method is requested for long-term traceability and good
      reproducibility of the predictive value. Therefore, it is crucial to watch
      changes in the path length under a fixed path length as a reference. From this
      standpoint, modified MSC, which uses a particular spectrum as a reference instead
      of the average spectrum of a sample set, was proposed in the present study, and
      it was demonstrated that the variations due to the individual differences in the
      vials can not only be compensated, but the path lengths of vials could also be
      estimated by the modified MSC. Moreover, a calibration model for the toluene
      concentration in silicone oil was developed to confirm the effects of modified
      MSC by using another sample set. The results showed that the compensation of vial
      path lengths using the modified MSC is also useful for other samples, similar to
      the case of the sample of IPA in toluene.

PMID- 17456259
TI  - Spectral simulation methodology for calibration transfer of near-infrared
      spectra.
AB  - A spectrum simulation method is described for use in the development and transfer
      of multivariate calibration models from near-infrared spectra. By use of
      previously measured molar absorptivities and solvent displacement factors,
      synthetic calibration spectra are computed using only background spectra
      collected with the spectrometer for which a calibration model is desired. The
      resulting synthetic calibration set is used with partial least squares regression
      to form the calibration model. This methodology is demonstrated for use in the
      analysis of physiological levels of glucose (1-30 mM) in an aqueous matrix
      containing variable levels of alanine, ascorbate, lactate, urea, and triacetin.
      Experimentally measured data from two different Fourier transform spectrometers
      with different noise levels and stabilities are used to evaluate the simulation
      method. With the more stable instrument (A), well-performing calibration models
      are obtained, producing a standard error of prediction (SEP) of 0.70 mM. With the
      less stable instrument (B), the calibration based solely on synthetic spectra is
      less successful, producing an SEP value of 1.58 mM. For cases in which the
      synthetic spectra do not describe enough spectral variance, an augmentation
      protocol is evaluated in which the synthetic calibration spectra are augmented
      with the spectra of a small number of experimentally measured calibration
      samples. For instruments A and B, respectively, augmentation with measured
      spectra of nine samples lowers the SEP values to 0.64 and 0.85 mM.

PMID- 17456260
TI  - Transfer of near-infrared calibration model for determining fiber content in
      flax: effects of transfer samples and standardization procedure.
AB  - The transfer of a calibration model for determining fiber content in flax stem
      was accomplished between two near-infrared spectrometers, which are the same
      brand but which require a standardization. In this paper, three factors,
      including transfer sample set, spectral type, and standardization method, were
      investigated to obtain the best standardization result. Twelve standardization
      files were produced from two sets of the transfer sample (sealed reference
      standards and a subset of the prediction set), two types of the transfer sample
      spectra (raw and preprocessed spectra), and three standardization methods (direct
      standardization (DS), piecewise direct standardization (PDS), and double window
      piecewise direct standardization (DWPDS)). The efficacy of the model transfer was
      evaluated based on the root mean square error of prediction, calculated using the
      independent prediction samples. Results indicated that the standardization using
      the sealed reference standards was unacceptable, but the standardization using
      the prediction subset was adequate. The use of the preprocessed spectra of the
      transfer samples led to the calibration transfers that were successful,
      especially for the PDS and the DWPDS correction. Finally, standardization using
      the prediction subset and their preprocessed spectra with DWPDS correction proved
      to be the best method for transferring the model.

PMID- 17456261
TI  - Detection of trace water vapor in high-purity phosphine using cavity ring-down
      spectroscopy.
AB  - The presence of trace water vapor in process gases such as phosphine, used for
      compound semiconductor epitaxial growth, can negatively affect the optical and
      electrical properties of the final device. Therefore, sensitive H2O measurement
      techniques are required to monitor precursor purity and detect unacceptable
      contamination levels. A commercial cavity ring-down spectrometer that monitors an
      H2O absorption line at a wavelength of 1392.53 nm was investigated for service in
      high purity PH3. Spectral parameters such as the line shape of water vapor in the
      presence of PH3 as well as background features due to PH3 were measured at
      different pressures and incorporated into the data analysis software for accurate
      moisture readings. Test concentrations generated with a diffusion vialbased H2O
      source and dilution manifold were used to verify instrument accuracy,
      sensitivity, linearity, and response time. H2O readings at 13.2 kPa corresponded
      well to added concentrations (slope=0.990+/-0.01) and were linear in the tested
      range (0-52.7 nmol mol-1). The analyzer was sensitive to changes in H2O
      concentration of 1.3 nmol mol-1 based on 3sigma of the calibration curve
      intercept for a weighted linear fit. Local PH3 absorption features that could not
      be distinguished from the H2O line were present in the purified PH3 spectra and
      resulted in an additional systematic uncertainty of 9.0 nmol mol-1. Equilibration
      to changing H2O levels at a flow rate of 80 std cm3 min-1 PH3 occurred in 10-30
      minutes. The results indicate that cavity ring-down spectroscopy (CRDS) at
      1392.53 nm may be useful for applications such as on-line monitoring (and dry
      down) of phosphine gas delivery lines or the quality control of cylinder sources.

PMID- 17456262
TI  - Measurements of collisional broadening coefficients by infrared polarization
      spectroscopy.
AB  - We present measurements of collisional broadening coefficients, obtained at
      atmospheric pressure, by polarization spectroscopy. Using tunable single mode
      laser radiation at approximately 2 microm, high-resolution infrared polarization
      spectra were recorded for CO2-Ar and CO2-He binary mixtures. The recorded
      polarization spectra were fitted with a Lorentzian cubed function form to obtain
      the broadening coefficients. The full-width at half-maxima (FWHM) collisional
      broadening rates of CO2 by Ar and He, for the R14 (12 degrees1<--00 degrees0)
      line, have been determined to be 0.161+/-0.018 cm-1 atm-1 and 0.1823+/-0.0032 cm
      1 atm-1, respectively.

PMID- 17456263
TI  - Bayesian maximum entropy (two-dimensional) lifetime distribution reconstruction
      from time-resolved spectroscopic data.
AB  - Time-resolved spectroscopy is often used to monitor the relaxation processes (or
      reactions) of physical, chemical, and biochemical systems after some fast
      physical or chemical perturbation. Time-resolved spectra contain information
      about the relaxation kinetics, in the form of macroscopic time constants of decay
      and their decay associated spectra. In the present paper we show how the Bayesian
      maximum entropy inversion of the Laplace transform (MaxEnt-iLT) can provide a
      lifetime distribution without sign-restrictions (or two-dimensional (2D)-lifetime
      distribution), representing the most probable inference given the data. From the
      reconstructed (2D) lifetime distribution it is possible to obtain the number of
      exponentials decays, macroscopic rate constants, and exponential amplitudes (or
      their decay associated spectra) present in the data. More importantly, the
      obtained (2D) lifetime distribution is obtained free from pre-conditioned ideas
      about the number of exponential decays present in the data. In contrast to the
      standard regularized maximum entropy method, the Bayesian MaxEnt approach
      automatically estimates the regularization parameter, providing an unsupervised
      and more objective analysis. We also show that the regularization parameter can
      be automatically determined by the L-curve and generalized cross-validation
      methods, providing (2D) lifetime reconstructions relatively close to the Bayesian
      best inference. Finally, we propose the use of MaxEnt-iLT for a more objective
      discrimination between data-supported and data-unsupported quantitative kinetic
      models, which takes both the data and the analysis limitations into account. All
      these aspects are illustrated with realistic time-resolved Fourier transform
      infrared (FT-IR) synthetic spectra of the bacteriorhodopsin photocycle.

PMID- 17456264
TI  - Portable radiometer: a novel technique for in situ band gap measurements.
AB  - Portable radiometers are commonly used in remote sensing applications for
      studying vegetation, soil, minerals, etc. However, we propose and demonstrate,
      for the first time, the applicability of this radiometer for high-resolution in
      situ band gap measurements of materials. The excitation source can be any white
      light source such as sun or tungsten halogen lamp. The flexibility in sample size
      and relative ease of varying temperature during measurements add to the
      advantages of using a portable radiometer for investigating new materials.
      Accurate measurements were made on standard samples of silicon, germanium, and
      gallium antimonide to demonstrate the feasibility of this technique.

PMID- 17456265
TI  - Simple and reliable Raman measurement of an etchant solution directly through
      teflon tubing.

PMID- 17456266
TI  - Application of a fluorescence assay for the quantification of the photodynamic
      agent photofrin in horses.

PMID- 17456267
TI  - Personality and music: can traits explain how people use music in everyday life?
AB  - This paper reports the results of a study on the relationship between individual
      differences and specific uses of music, referring to why and how people use music
      in everyday life. Questionnaire data from 341 respondents showed that open and
      intellectually engaged individuals, and those with higher IQ scores, tended to
      use music in a rational/cognitive way, while neurotic, introverted and non
      conscientious individuals were all more likely to use music for emotional
      regulation (e.g. change or enhance moods). Results suggest that individual
      differences in personality and cognitive ability may partly determine the way in
      which we experience music. Limitations and suggestions for future studies are
      discussed.

PMID- 17456268
TI  - A comparative study of body image of Australian and Pakistani young females.
AB  - This research compares Australian and Pakistani females on body image attitudes.
      The sample consisted of Caucasian-Australian and Pakistani first year university
      students, ranging in age from 17 to 22. The Pakistani sample was subdivided into
      two groups: Urdu-medium and English-medium, representing the middle and upper
      social classes, respectively. The results revealed that, although all the groups
      identified a similar body shape as the 'ideal', the Australian females expressed
      significantly higher levels of body dissatisfaction on all measures of body image
      than did the Pakistani females. Within the Pakistani sample, females from the
      English-medium institutions expressed greater weight concern than did the Urdu
      medium females. The findings are discussed in terms of the possible role of
      cultural values in shaping the body image attitudes of young females.

PMID- 17456269
TI  - Rimes and superrimes: an exploration of children's disyllabic rhyming skills.
AB  - The study investigated the extension of rhyme awareness to disyllabic stimuli.
      Three experiments are reported which examine the disyllabic rhyme production
      skills of adults and of children in their first, second or third year of
      schooling. Stress pattern and phonological rime and superrime neighbourhood
      density were manipulated. Rhyming skills were influenced by stress pattern. With
      initial stress, rhyming responses were based predominantly on the superrime but
      with final stress, rhyming responses variously shared the superrime, the final
      syllable and the final rime unit with the target. Neighbourhood density affected
      the likelihood of production of a real word rhyming response. Some implications
      for the organization of an orthographic lexicon of multisyllables are discussed.

PMID- 17456270
TI  - Sex differences in the effects of interest on boys' and girls' reading
      comprehension.
AB  - This study compared the reading comprehension of groups of boys and girls (aged
      10-11) on two tests, one of which was about the evacuation of children during the
      Second World War and the other of which was about spiders. These were the actual
      year 6 SATS reading tests administered in the UK in 1998 and 1999. The majority
      of the boys said that they would prefer to read the text about spiders, and the
      majority of the girls said they would prefer to read the text about leaving home
      in wartime. These patterns of preference were reflected in the children's
      performance on the actual tests. However, whereas the boys' comprehension was
      significantly affected by the content of the tests (they showed better
      performance on the test about spiders) the girls' performance was relatively
      little influenced by the content of the test. The implications of these results
      for testing reading, and for encouraging reading more generally, are discussed.

PMID- 17456271
TI  - Empathizing and systemizing: what are they, and what do they contribute to our
      understanding of psychological sex differences?
AB  - Empathizing and systemizing have recently been put forward as two important
      individual-difference dimensions, whose different mean levels in men and women
      are argued to account for many psychological sex differences. This paper presents
      a series of studies designed to investigate the reliability and validity of the
      empathizing and systemizing quotients (EQ & SQ), to relate them to existing
      personality constructs, and to replicate reported sex and sexual orientation
      related differences. Correlations with interests and social behaviour suggest the
      two measures are valid. However, empathizing appears essentially equivalent to
      agreeableness in the five-factor model of personality. Systemizing cannot be
      reduced to established personality dimensions, though it is moderately correlated
      with conscientiousness and openness. Men have higher levels of systemizing than
      women, and non-heterosexual women higher than heterosexuals. However, no
      differences were found between heterosexual and non-heterosexual men. Although
      systemizing and empathizing account for a number of observed sex differences,
      there are others they do not explain.

PMID- 17456272
TI  - Effects of post-cue interval on intentional forgetting.
AB  - This study examined the effect of post-cue interval on directed forgetting and
      suppression. Experiments 1 and 2 used the item method of directed forgetting. The
      interval between the cue to remember/forget (R/F) and the presence of the next
      item was manipulated. As the post-cue interval increased, the rates of hits and
      'remember' responses on the recognition test also increased not only for R items
      but also for F items, suggesting that participants did not stop processing F
      items after the F cue. Experiment 3 manipulated both the number of
      response/suppression attempts and the duration of response/suppression for each
      word pair during the response/suppression phase. The results showed that
      increasing the number of suppression attempts led to worse recall in the
      subsequent memory test. However, increasing the duration of suppression reduced
      the suppression effect. These results provide insights into a key factor for
      successful intentional forgetting and suppression.

PMID- 17456273
TI  - The location of trait emotional intelligence in personality factor space.
AB  - The construct of trait emotional intelligence (trait EI or trait emotional self
      efficacy) provides a comprehensive operationalization of emotion-related self
      perceptions and dispositions. In the first part of the present study (N=274, 92
      males), we performed two joint factor analyses to determine the location of trait
      EI in Eysenckian and Big Five factor space. The results showed that trait EI is a
      compound personality construct located at the lower levels of the two taxonomies.
      In the second part of the study, we performed six two-step hierarchical
      regressions to investigate the incremental validity of trait EI in predicting,
      over and above the Giant Three and Big Five personality dimensions, six distinct
      criteria (life satisfaction, rumination, two adaptive and two maladaptive coping
      styles). Trait EI incrementally predicted four criteria over the Giant Three and
      five criteria over the Big Five. The discussion addresses common questions about
      the operationalization of emotional intelligence as a personality trait.

PMID- 17456274
TI  - Characterizing linguistic structure with mutual information.
AB  - We explore mutual information (MI) as a means of characterizing linguistic
      statistical structure. The MI between two linguistic tokens x and y is the degree
      to which seeing x helps us anticipate the occurrence of y. We computed MI between
      words in 595 samples of written text in 25 languages. Our analyses indicate that
      MI dependencies do not extend beyond a range of five words. Moreover, the
      similarity between MI profiles of different languages was used to cluster the
      languages. These results are discussed in terms of a putative link between short
      term memory and linguistic structure and the further utility of MI in terms of
      characterizing the latter.

PMID- 17456275
TI  - Predicting children's word-spelling difficulty for common English words from
      measures of orthographic transparency, phonemic and graphemic length and word
      frequency.
AB  - Spencer demonstrated that spelling and reading difficulty for English words can
      be predicted from a number of factors, including word frequency, phonemic length
      and measures of orthographic depth and complexity. In this study, spelling
      difficulty of high frequency words was investigated across five year groups (ages
      7 to 11 years) with a wide ranging series of data sources from which to determine
      word frequency values and orthographic depth measures. A regression model
      accounted for 52-66% of the variance for 7- to 11-year-olds and 72% of the
      variance for the lowest performing quartile group, irrespective of age. The most
      influential factor, phonetic difference (being the difference in the number of
      letters and phonemes in a word, and representing grapheme complexity), links the
      relative influence of large graphemic units in foundation literacy to a similar
      phenomenon, the 'whammy' effect, which provides support for serial processing in
      the dual route cascade model of word recognition in skilled readers (Rastle &
      Coltheart, 1998). The study supports recent research on European orthographies,
      which concludes that both orthographic depth and complexity contribute to delayed
      acquisition of foundation literacy skills.

PMID- 17456276
TI  - Kinship and altruism: a cross-cultural experimental study.
AB  - Humans are characterized by an unusual level of prosociality. Despite this,
      considerable indirect evidence suggests that biological kinship plays an
      important role in altruistic behaviour. All previous reports of the influence of
      kin selection on human altruism have, however, used correlational (rather than
      experimental) designs, or imposed only a hypothetical or negligible time cost on
      participants. Since these research designs fail either to control for confounding
      variables or to meet the criteria required as a test of Hamilton's rule for kin
      selection (that the altruist pays a true cost), they fail to establish
      unequivocally whether kin selection plays a role. We show that individuals from
      two different cultures behave in accordance with Hamilton's rule by acting more
      altruistically (imposing a higher physical cost upon themselves) towards more
      closely related individuals. Three possible sources of confound were ruled out:
      generational effects, sexual attraction and reciprocity. Performance on the task
      however did not exhibit a perfect linear relationship with relatedness, which
      might reflect either the intrusion of other variables (e.g. cultural differences
      in the way kinship is costed) or that our behavioural measure is insufficiently
      sensitive to fine-tuned differences in the way individuals view their social
      world. These findings provide the first unequivocal experimental evidence that
      kinship plays a role in moderating altruistic behaviour. Kinship thus represents
      a baseline against which individuals pitch other criteria (including reciprocity,
      prosociality, obligation and a moral sense) when deciding how to behave towards
      others.

PMID- 17456277
TI  - Minds and gaps.

PMID- 17456278
TI  - Economic development and inequality affect IQ. A response to Kanazawa.

PMID- 17456279
TI  - Mind the gap(s)... in theory, method and data: Re-examining Kanazawa (2006).
AB  - Kanazawa (2006) has put forward an evolutionarily grounded theory which claims
      that individuals in wealthier and more egalitarian societies live longer and stay
      healthier not because they are wealthier or more egalitarian but because they are
      more intelligent (2006: 637). The claim rests on an argument which asserts that
      general intelligence is a solution to evolutionarily novel problems and that most
      dangers to health in contemporary society are evolutionarily novel. Kanazawa also
      claims that this relationship does not hold in sub-Saharan Africa. These claims
      are based on a cross-national analysis which finds a positive correlation between
      'national' IQ scores and mortality data. The implication is that intelligence is
      the principal factor determining longevity in the rest of the world, regardless
      of issues such as adequacy of diet and availability of health care. Kanazawa's
      theoretical claims about the evolution of general intelligence as a domain
      specific adaptation are inconsistent with adaptationist analysis: natural
      selection does not solve general problems. The assumptions that sub-Saharan
      Africa is more representative of the evolutionary past than is the rest of the
      world, and that most hazards to health in contemporary society are evolutionarily
      novel, are implausible. The methods used are inadequate because Kanazawa argues
      for causation from correlation and fails to consider alternative explanations.
      The IQ data are flawed for reasons to do with sample size and sampling,
      extrapolation and inconsistency across measures. Nor are they temporally
      compatible with the economic and demographic data.

PMID- 17456280
TI  - Literacy not intelligence moderates the relationships between economic
      development, income inequality and health.
AB  - OBJECTIVES: Kanazawa (2006) presented data allegedly supporting a racist version
      of evolutionary psychology that claims that the populations of wealthier and more
      egalitarian societies live longer and stay healthier, not because they are
      wealthier and more egalitarian, but because they are more intelligent. The
      objectives of this study are: (i) to determine the relationship between IQ and
      literacy in Kanazawa's sample of countries and (ii) to reanalyse Kanazawa's
      dataset using measures of literacy in lieu of national IQ test scores. METHOD:
      Correlation and regression were employed. RESULTS: National literacy scores
      across the countries in the sample are highly skewed. In spite of this, the
      literacy measures are highly correlated with alleged differences in national IQ
      (r = .83-.86). The measure of literacy together with economic development (GDPpc)
      and income inequality (Gini coefficient) control at least 59-64% of the variance
      in national life expectancy at birth. CONCLUSIONS: There is no scientific
      justification for believing that alleged intelligence differences play any role
      in explaining international differences in health status. Measures of alleged
      national IQ scores are highly confounded with differences in literacy. Literacy
      is a key factor in the health of any community and policies designed to enhance
      the literacy of a population are expected to lead to significant improvements in
      health status.

PMID- 17456281
TI  - A commentary on Satoshi Kanazawa's study of intelligence and health.
AB  - We provide an exposition of the major conceptual, methodological and statistical
      shortcomings of the paper by Kanazawa (2006), concerning the relationship between
      intelligence and life expectancy. It is argued that the validity and robustness
      of the conclusions of the paper are compromised by fundamental problems,
      including failure to present competing views with fair balance, use of samples of
      convenience to draw conclusions about populations, performing tests of
      significance when there is no theoretical basis to do so and confusing
      association with causation. Given the far-reaching socio-economic implications of
      the conclusions, it is suggested that the messages of the paper be critically
      evaluated in relation to the major limitations of the research.

PMID- 17456282
TI  - Health, wealth and IQ in sub-Saharan Africa: challenges facing the 'Savanna
      Principle' as an explanation for global inequalities in health.
AB  - Kanazawa's (2006) national- and individual-level analyses seem to support his
      hypothesis that: IQ scores are better predictors of health than wealth or
      inequality, except in 'evolutionarily familiar' sub-Saharan Africa which offers
      limited selection for intelligence (British Journal of Health Psychology 11: 623
      42). However, the present paper exposes the flawed assumptions, questionable
      data, inappropriate analyses and biased interpretations on which this thesis was
      based. It questions the assumptions that: IQ scores are markers of adaptive
      genetic differences in intelligence; humans evolved within a predictable
      'environment of evolutionary adaptedness': and this environment characterizes
      contemporary sub-Saharan Africa, offering little selection for intelligence. It
      also demonstrates that the macro-level data on which these analyses were based
      were collected across a range of different years, using a range of different
      sources, and were significantly intercorrelated. While none of these analyses
      adjusted for study year or study type, all were susceptible to multicollinearity
      and the 'ecological fallacy'. These flaws were compounded by the selective
      presentation and partial interpretation of the analyses, which focused on the
      absence of an 'independent' relationship between 'national IQ' and health within
      sub-Saharan Africa, but ignored the fact that this is also true for every other
      region of the world. Likewise, the individual-level analyses did not explore the
      relationship between IQ scores, self-reported income and health by race, which
      would have demonstrated the impact of the ecological fallacy. Instead, Kanazawa
      (2006) mistook statistical associations for evidence of causality and falsely
      concluded that populations in sub-Saharan Africa are less healthy because they
      are unintelligent and not because they are poor.

PMID- 17456283
TI  - Are modern health worries, personality and attitudes to science associated with
      the use of complementary and alternative medicine?
AB  - OBJECTIVE: To investigate whether personality traits, modern health worries
      (MHWs) and attitudes to science predict attitudes to, and beliefs about,
      complementary and alternative medicine (CAM). This study set out to test whether
      belief in, and use of CAM was significantly associated with high levels of MHWs,
      a high level of neuroticism and sceptical attitudes towards science. METHODS: Two
      hundred and forty-three British adults completed a four part questionnaire that
      measured MHWs, the Big Five personality traits and beliefs about science and
      medicine and attitudes to CAM. RESULTS: There were many gender differences in
      MHWs (females expressed more), though results were similar to previous studies.
      Contrary to prediction, personality traits were not related to MHWs, CAM usage or
      beliefs about CAM. Regular and occasional users of CAM did have higher MHWs than
      those non or infrequent users. Those with high totalled MHWs also tended to
      believe in the importance of psychological factors in health and illness, as well
      as the potential harmful effects of modern medicine. Young males who had positive
      attitudes to science were least likely to be CAM users. Further, positive
      attitudes to science were associated with increased scepticism about CAM.
      CONCLUSION: Concern about health, belief about modern medicine and CAM are
      logically inter-related. Those who have high MHWs tend to be more sceptical about
      modern medicine and more convinced of the possible role of psychological factors
      in personal health and illness.

PMID- 17456284
TI  - Daily patterns of symptom reporting in families with adolescent children.
AB  - OBJECTIVES: This study was designed to investigate how symptom reporting varies
      by time of day, day of the week, gender and generation. DESIGN: Concurrent
      symptom reporting was assessed prospectively using a computer-assisted self
      report method. METHODS: A computer-assisted self-observation method was used to
      assess concurrent somatic complaints six times a day for 7 consecutive days.
      Parents and adolescents from 173 families (568 individuals) filled in
      questionnaires during a normal workweek. A generalized linear model approach for
      multi-level models was used to analyse the multiple daily observations. RESULTS:
      Results show a curvilinear within-day pattern for the reporting of somatic
      complaints, such that complaints were reported most in the morning and evening
      and least in the middle of the day. On weekends, participants reported fewer
      complaints in the evening. Women reported more symptoms throughout the day.
      Adolescents show an earlier and more pronounced increase in symptom reporting
      towards the evening. In addition, a slight decline in symptom reporting over the
      observation period was observed. CONCLUSIONS: Symptom reporting changes
      throughout the day, and is influenced by gender, generation and day of the week.

PMID- 17456285
TI  - How do you explain a pain that can't be seen?: the narratives of women with
      chronic pelvic pain and their disengagement with the diagnostic cycle.
AB  - OBJECTIVES: Chronic pelvic pain (CPP) has an adverse effect on women's quality of
      life. Research has suggested that many women become dissatisfied with their care
      and withdraw from seeking help despite continuing symptoms. The aim of this study
      was to explore the processes which lead to disengagement and to understand the
      psychosocial processes that affect this group of women. DESIGN: A qualitative
      narrative approach was used, guided by phenomenological-hermeneutic tradition,
      and informed by the philosophy of Paul Ricoeur. METHOD: Thirty-two women with CPP
      were asked to write their stories about their illness trajectories. These written
      stories served as data which were analysed thematically according to narrative
      theory. RESULTS: In the search for validation and recognition women engaged in
      the diagnostic cycle. Many women do not complete this cycle, become stuck at a
      certain point, or re-enter the cycle repeatedly. They can only opt out if the
      problem is resolved or by choosing to disengage with medical care. CONCLUSIONS:
      While the medical consultation was a dominant theme, a complex interaction of
      factors was required to initiate disengagement. The dualistic nature of the
      diagnostic process prohibits women from telling their stories. Women were left
      feeling disempowered and in limbo, and they were at a loss as to how to manage
      their pain.

PMID- 17456286
TI  - Showing smokers with vascular disease images of their arteries to motivate
      cessation: a pilot study.
AB  - OBJECTIVE: To examine the potential impact of visual personalized biomarker
      feedback on intention to stop smoking and to evaluate possible underlying causal
      pathways. DESIGN: This study is a pilot for a randomized controlled trial.
      Outcome measures were assessed immediately after the intervention and at 4 weeks
      follow-up. METHOD: Twenty-three smokers attending a cardiovascular outpatient
      clinic in London were randomly allocated to one of two groups: to either receive
      a print-out of an ultrasound image of their carotid artery showing
      atherosclerotic plaque alongside an image of a disease-free artery, or to receive
      routine verbal feedback. RESULTS: The intervention significantly increased
      perceptions of susceptibility to smoking-related diseases (Cohen's h=0.99) and
      led to increases both in engagement in smoking cessation behaviours (Cohen's
      h=0.79) and intentions to stop smoking (Cohn's d=0.44). The latter was moderated
      by self-efficacy: the intervention increased intention to stop smoking only in
      people with higher levels of self-efficacy with regard to stopping smoking.
      CONCLUSIONS: This study provides preliminary support for the potential
      effectiveness of personalized biomarker feedback to increase intentions to stop
      smoking. It also highlights the need to target and increase self-efficacy in
      smoking cessation interventions.

PMID- 17456287
TI  - Information processing of food cues in overweight and normal weight adolescents.
AB  - OBJECTIVES: Based on cognitive theory (CT), the aim of this study is to
      investigate the cognitive processing of food cues in clinically overweight
      adolescents. DESIGN: An experimental design with performance-based measures.
      METHODS: Eighty-seven (45 overweight, 42 normal weight) adolescents between the
      ages of 12 and 18 years were examined. All completed an imbedded word task (IWT),
      containing high caloric food words and matched control words, as a measure of
      attention interference. A free-recall task was used to detect explicit memory
      biases. To study the effects of cognitive avoidance, participants were instructed
      to suppress thoughts about food or merely to monitor them, prior to completing
      the IWT and memory task. RESULTS: No evidence was found for interference in the
      attention processing of food cues. Also, no effects of thought suppression were
      found. However, consistent with hypotheses, the overweight adolescents did show
      an explicit memory bias for food stimuli, not due to a more general negative
      evaluation of food words. CONCLUSIONS: The results provide at least partial
      support for the applicability of CT to adolescent obesity. The study was the
      first to reveal a memory bias for high caloric food cues in overweight
      youngsters, which may well reflect a later-stage activation of food-related
      schemata. These may play a role in food-related preoccupations and overeating.
      The existence of an early-stage attention bias is less clear and requires further
      investigation.

PMID- 17456288
TI  - Why do heterosexual young adults who use reliable contraception also use condoms?
      Results from a diary-based prospective longitudinal study.
AB  - OBJECTIVES: To identify characteristics of individuals and characteristics of
      sexual encounters that predict whether people using contraception will also use
      condoms (dual use), and to determine whether dual use is prompted by concerns
      about unplanned pregnancy and/or sexually transmitted infections (STIs). DESIGN:
      A longitudinal prospective design was used to identify characteristics of
      individuals and characteristics of specific sexual encounters that predict condom
      use. METHODS: A sample of 349 sexually active heterosexual young adults was
      recruited at universities and trade colleges in Melbourne, Australia.
      Participants completed a self-administered questionnaire, and a representative
      subsample (N=103) completed a structured condom use diary in which they reported
      on up to 10 instances of vaginal intercourse. Respondents reported use of condoms
      and other forms of contraception during 919 instances of vaginal intercourse.
      RESULTS: In multivariate analyses, dual use of condoms in addition to other
      contraception was predicted by attitudes toward condoms, intentions to use
      condoms, partner type and discussion of condom use with sexual partners. Dual use
      was not related to greater concern about HIV/STIs or unplanned pregnancy.
      CONCLUSIONS: Encouraging heterosexual young adults to discuss condom use, and
      developing their skills for negotiation of condom use will increase rates of
      condom use, thereby reducing current high rates of unplanned pregnancy and STIs.

PMID- 17456289
TI  - Thyroid-stimulating hormone assays: guidelines, guidance and clinical judgement.

PMID- 17456290
TI  - Thyroid guidelines - are thyroid-stimulating hormone assays fit for purpose?
AB  - Most thyroid-stimulating hormone (TSH) assays now have the sensitivity required
      by thyroid guidelines and allow the reliable identification of patients with both
      overt and subclinical hyperthyroidism. Clinical guidelines usually quote decision
      limits for TSH, but often ignore the issue of whether variability in bias between
      assays should be considered when such decision limits are implemented. Clinicians
      and laboratories should appreciate that these decision limits arise largely from
      historical data that used TSH assays with poorly defined bias. It is thus
      unlikely that laboratories will be able to apply an appropriate method-related
      bias adjustment to these TSH cut-offs. Clinicians should appreciate that TSH
      decision limits should thus be regarded as typical target figures rather than an
      absolute cut-off and thus can be applied with some degree of flexibility. There
      is currently insufficient evidence to justify a significant lowering of the upper
      reference limit for TSH, but fine-tuning of current reference ranges is required
      since there appears to be no association between the ranking of the assay bias in
      the UK National External Quality Assessment Service scheme and the manufacturers'
      quoted reference ranges. There is room for further improvement in TSH assays and
      this can best be achieved if manufacturers, laboratories and clinicians work
      together to produce TSH assays and reference ranges that show closer agreement
      between methods. Until this is achieved, future studies that examine the
      relationship of TSH with symptoms and treatment should ensure that sufficient
      information is included in the publication to allow the method related bias of
      the TSH assay to be clearly described.

PMID- 17456291
TI  - Overview on robotics in the laboratory.
AB  - This review provides a short history of the development of robotic systems in
      Clinical Chemistry and discusses the early expectations for these systems. The
      systems currently available are discussed and every attempt has been made to keep
      this section up-to-date, but this is a constantly changing field. Much of the
      review is taken up looking at the impact resulting from the introduction of
      robotic systems in the laboratory and whether they have met the expectations of
      the laboratory. It is difficult to get hard data since laboratories are most
      concerned with getting their instrumentation up and running and there is little
      time, or thought given, to pre- and post-introduction studies. Therefore, the
      literature is sparse but much of the data for the UK has come from a Medicines
      and Healthcare products Regulatory Agency (MHRA) review of pre-analytical
      systems. Finally thought has been given to future developments and their possible
      impact on the functioning of the laboratory.

PMID- 17456292
TI  - The basis and management of metabolic abnormalities associated with
      cardiovascular risk in human immunodeficiency virus infection and its treatment.
AB  - The high global prevalence of human immunodeficiency virus (HIV) infection has
      been associated with high morbidity and mortality. The advent of highly active
      antiretroviral therapy (HAART) has, however, dramatically increased survival of
      patients infected with HIV. These patients now survive to develop metabolic
      complications of HIV infection and its treatment, including increased
      predisposition to atherosclerotic disease. HIV infection is normally associated
      with hypocholesterolaemia, hypertriglyceridaemia, low plasma HDL-cholesterol as
      well as alterations in other cardiovascular risk factors including inflammatory
      markers, clotting factors, homocysteine, apolipoproteins, lipoprotein (a),
      oxidative stress and non-esterified fatty acids. The use of HAART is, in
      particular, associated with dyslipidaemia and lipodystrophy with underlying
      insulin resistance and associated glucose intolerance. This article explores the
      metabolic abnormalities associated with increased cardiovascular risk that occur
      in HIV infection before and after antiretroviral therapy. The laboratory
      investigation and clinical management of HIV-associated dyslipidaemia and
      lipodystrophy will be discussed.

PMID- 17456293
TI  - Metabolic syndrome and cardiovascular disease.
AB  - The clustering of metabolic and pathophysiological cardiovascular risk factors
      has long been recognized but it was Reaven who popularized the syndrome in the
      Banting lecture of 1988. Since 1999, several major international or national
      organizations proposed their own definitions for the syndrome, named the
      metabolic syndrome. The prevalence of the metabolic syndrome varies according to
      definition, ethnicity and gender. The prevalence is under 20% among Chinese and
      Korean people but over 50% among Maori and Pacific Islanders in New Zealand.
      People with the metabolic syndrome have 50-60% higher cardiovascular risk than
      those without. The absolute cardiovascular risk of the metabolic syndrome,
      however, is not necessarily higher than those of its individual components. The
      pathogenesis underlying the clustering of cardiovascular risk factors remains
      unclear. Factors including genetic disposition, obesity, insulin resistance and
      inflammation have been suggested as being involved. Since the metabolic syndrome
      is multifactorial in origin, strategies for reducing cardiovascular risk in
      individuals with the metabolic syndrome involve the management of multiple risks.
      Lifestyle changes are an effective first-line management; pharmacological
      interventions for hypertension, diabetes and dyslipidaemia are in accordance with
      established guidelines. Pharmacological and surgical therapies for obesity are
      effective in selected patients. In this article we discuss the definitions,
      prevalence, pathogenesis and management of the metabolic syndrome in relation to
      cardiovascular risk.

PMID- 17456294
TI  - Osteopontin and C-reactive protein in Egyptian patients affected with tuberculous
      and malignant pleural effusion.
AB  - BACKGROUND: The first step in the evaluation of patients with pleural effusion is
      to determine whether the effusion is a transudate or an exudate. Osteopontin
      (OPN) is a pleiotropic integrin-binding protein with many functions. We assessed
      pleural effusion and serum concentrations of OPN and C-reactive protein (CRP) in
      patients with different types of pleural effusions. METHODS: The current study
      comprised three groups: 20 patients with transudative effusion, 30 patients with
      malignant effusion and 30 patients with tuberculous effusion. OPN was analysed
      using a commercially available enzyme-linked immunosorbent assay kit. RESULTS:
      OPN effusion values were significantly higher in exudates (both malignant and
      tuberculous effusion cases) compared with transudative effusion. Also when
      compared separately, patients with tuberculous effusion and those with malignant
      effusion had a significantly higher fluid and OPN effusion/serum ratio than those
      with transudative effusion. Patients with tuberculous effusion had a
      significantly higher serum CRP effusion and effusion/serum ratio of CRP than
      those with malignant or transudative effusion. CONCLUSION: OPN is significantly
      increased in exudative effusion compared with transudative ones. However, serum
      OPN and effusion/serum OPN ratio were not significantly different in patients
      with malignant from those with tuberculous effusions. The lack of difference in
      serum OPN and effusion/serum OPN ratio between patients with malignant and those
      with tuberculous effusion may be attributed to the heterogeneity of the malignant
      effusion group. Receiver-operating characteristic (ROC) curve analysis has shown
      that effusion/serum CRP ratio outperformed effusion/serum OPN ratio as a
      diagnostic marker for tuberculous pleural effusion.

PMID- 17456295
TI  - Provision of laboratory services for lipid analysis in the United Kingdom.
AB  - BACKGROUND: National guidelines have been developed in the UK to reduce coronary
      heart disease mortality. This audit assesses provision of lipid analyses by UK
      Clinical Biochemistry services to support their implementation. METHODS: Audit
      standards were derived from published guidelines. A questionnaire based on these
      was circulated to all UK Clinical Biochemistry laboratories. RESULTS: Of 108
      replies, routine lipid profiles included triglycerides, HDL-, LDL-cholesterol and
      total:HDL cholesterol ratio in 98, 85, 72 and 44%, respectively. Only 33% and 27%
      analysed triglycerides and HDL, respectively, when asked simply to measure
      cholesterol. Seventy-six percent of the reports stated whether specimens were
      collected after fasting. For primary prevention, 46% of laboratories stated
      results should be interpreted in association with other risk factors; 20%
      referred explicitly to national/local guidelines. Only 19 laboratories quoted
      secondary prevention treatment thresholds for total cholesterol or LDL
      cholesterol. Sixty laboratories occasionally added extra tests and/or
      interpretive comments. Eight laboratories appeared to provide no input from
      senior medical/scientific staff into report validation. CONCLUSIONS: These
      results indicate scope for improvement in the provision of lipid analyses and of
      information to support their interpretation. We recommend laboratories should
      routinely provide LDL- and non-HDL-cholesterol results, and that reports should
      quote treatment thresholds/targets in keeping with current guidelines.

PMID- 17456296
TI  - Salivary cortisol reflects serum cortisol: analysis of circadian profiles.
AB  - BACKGROUND: Technical hurdles limit the characterization of key hormonal rhythms.
      Frequent sampling increases detection of changes in magnitude or circadian and
      ultradian patterns, but limits feasibility for clinical or research settings.
      These caveats are particularly pertinent for cortisol, a hormone that displays a
      prominent circadian rhythm and whose magnitude is tightly regulated in the
      absence of biobehavioural challenge. Ideally, one would like to obtain samples
      non-invasively from a matrix of interest at frequent intervals. While many
      investigations have reported a high correlation between serum and salivary
      cortisol assays, the degree to which salivary cortisol reflects the circadian
      patterns of circulating cortisol concentrations has not been established across a
      24 h period. METHODS: We obtained hourly serum and salivary samples over a 24 h
      period in nine adults in an inpatient setting. The circadian patterns for serum
      and salivary cortisol were analysed by harmonic regression. RESULTS: For all but
      two subjects (both on oral contraceptives), the salivary cortisol concentration
      was synchronous with the serum concentration, indicating that the salivary assay
      could be substituted for the serum assay to assess circulating rhythmicity across
      the 24 h time frame. CONCLUSIONS: This statistical model has distinct improvement
      over the correlational approach of examining serum and saliva cortisol
      relationships. Saliva cortisol appears to represent serum cortisol across the 24
      h period, except for those on oral contraceptives.

PMID- 17456297
TI  - Newer cardiac troponin I assays have similar performance to troponin T in
      patients with end-stage renal disease.
AB  - BACKGROUND: Troponin T is present in the blood of a majority of patients with
      endstage renal disease (ESRD) undergoing regular dialysis and presence of
      troponin T is a predictor of adverse outcome in these patients. With several new
      formulations of troponin I assays available, this study was performed to see
      whether these newer assays were able to detect troponin I in these patients more
      effectively than the older assays. METHODS: One hundred and forty-three patients
      undergoing regular haemodialysis or peritoneal dialysis had plasma collected and
      troponin T and troponin I measured by a variety of assays. RESULTS: The newer
      troponin I assays (Abbott Architect, Bayer Centaur and Beckman Accu-TnI) were
      able to detect troponin I (>75% of samples) as effectively as the Roche assay was
      able to detect troponin T, while other troponin I assays had a much lower rate of
      detection of troponin - DPC Immulite 2000 16% and Abbott AxSYM 35%. However, the
      troponin T assay had more samples detected at concentrations corresponding to an
      assay CV of 10% (59% of samples) than did the newer troponin I assays (highest on
      the Bayer Centaur at 37%). CONCLUSIONS: Newer assays demonstrate that troponin I
      is present in a similar number of samples as is troponin T, in the blood of
      patients with dialysis-dependent renal failure, and these newer troponin I assays
      identify patients at risk of experiencing a cardiac event.

PMID- 17456298
TI  - General practitioner (GP) cardiac troponin test requesting: findings from a
      clinical laboratory audit.
AB  - BACKGROUND: There is limited data and literature on the issue of cardiac troponin
      test requesting by general practitioners (GPs). It was therefore our aim to audit
      the cardiac troponin test requests made by GPs in our community with a view to
      develop an informed strategy for assay provision and reporting of results.
      METHODS: A retrospective audit was undertaken of data in our laboratory database
      for all cardiac troponin T (cTnT) tests requested by GPs between January and June
      2005. A prospective audit was then carried out between July and December 2005
      using the telephone interview method. The number and distribution of tests, the
      reasons for the request and the intended action by the GPs were quantified.
      RESULTS: Forty-five of 46 of the results of both the retrospective and
      prospective audits were negative based on the 99th percentile level with less
      than 10% imprecision (cTnT <0.03 microg/L). During the one-year study period, we
      had requests from 24 general practices with a mean and mode of two and one
      requests per general practice respectively. The most common reason for the
      request was found to be chest pain that had occurred more than 24 h ago.
      CONCLUSION: Bearing in mind the limitations of an audit study, our findings
      obviate the use of cTnT in general practice. We suggest that the laboratory
      should liase with the GP and advise referral for specialist care if clinical
      suspicion of acute coronary syndrome is high.

PMID- 17456299
TI  - EDTA analysis on the Roche MODULAR analyser.
AB  - BACKGROUND: Patient specimens can be subject to subtle interference from cross
      contamination by liquid-based, potassium-containing EDTA anticoagulant, leading
      to misinterpretation of results. A rapid method for EDTA analysis to detect such
      contamination is described. METHOD: An in-house EDTA assay on the Roche MODULAR
      analyser was assessed for accuracy and precision by comparison with an adjusted
      calcium difference measurement (atomic absorption and o-cresolphthalein
      complexone colorimetry). RESULTS: EDTA method versus adjusted calcium difference
      showed: slope = 1.038 (95% confidence interval [CI] 0.949-1.131); intercept =
      0.073 (95% CI 0.018-0.132) mmol/L; r = 0.914; n = 94. However, inter-assay
      precision of the calcium difference method was estimated to be poorer
      (coefficient of variation 24.8% versus 3.4% for the automated colorimetric method
      at an EDTA concentration of 0.25 mmol/L). Unequivocal contamination was observed
      at an EDTA concentration of > or =0.2 mmol/L. The automated method showed
      positive interference from haemolysis and negative interference from oxalate. The
      method was unaffected by lipaemia (triglycerides <20 mmol/L), icterus (bilirubin
      <500 micromol/L), glucose (<100 mmol/L), iron (<100 micromol/L), and citrate,
      phosphate or fluoride (all <2.5 mmol/L). CONCLUSION: The automated colorimetric
      assay described is an accurate, precise and rapid (3 min) means of detecting EDTA
      contamination of unhaemolysed biochemistry specimens.

PMID- 17456300
TI  - The effect of potassium EDTA on the stability of parathyroid hormone in whole
      blood.
AB  - BACKGROUND: The stability of parathyroid hormone (PTH) in whole blood has not
      been well characterized. Previous studies show EDTA plasma samples to be more
      stable than serum samples. METHODS: Blood from 17 haemodialysis patients and five
      healthy volunteers was collected into serum separator tubes (SSTs) and potassium
      EDTA tubes (EDTA-Ts) and incubated at room temperature before separation and
      storage for PTH analysis using the Bayer Advia Centaur. RESULTS: Initial PTH
      concentrations were 7% higher (95% confidence interval [CI] 2-16%, P=0.016) in
      EDTA-Ts compared to the SSTs in the renal cohort. PTH concentrations in SSTs were
      significantly lower after 8 (10%, 95% CI 3-17%) and 20 h (22%, 95% CI 11-31%) but
      did not change significantly in EDTA-Ts (P=0.1543). PTH concentration in EDTA-Ts
      from healthy volunteers was also independent of incubation time (P=0.1165).
      CONCLUSION: The greater stability of PTH in whole blood anticoagulated with
      potassium EDTA allows PTH analysis to be offered to sites such as satellite
      clinics and primary care sites which do not have centrifugation and refrigeration
      facilities.

PMID- 17456301
TI  - Monitoring the treatment of carcinoid disease using blood serotonin and plasma 5
      hydroxyindoleacetic acid: three case examples.
AB  - The results for plasma 5-hydroxyindoleacetic acid (5-HIAA), whole blood serotonin
      and the chromogranins on three patients following their treatment for carcinoid
      disease with somatostatin analogues are presented. Two of the patients (a 56-year
      old woman and a 55-year-old man) demonstrated a good clinical response following
      treatment, with initial high blood serotonin and plasma 5-HIAA concentrations
      showing a significant decline. However, blood serotonin concentrations remained
      above the reference range during the course of treatment, whereas plasma 5-HIAA
      remained borderline high or marginally elevated with respect to the clinical cut
      off concentration. The third patient, a 79-year-old man, demonstrated saturation
      of platelets with serotonin and increasing elevation of plasma 5-HIAA, which
      later fell with the introduction of interferon into this patient's treatment
      regimen. Results for the plasma chromogranin fragments, pancreastatin
      (Chromogranin A) and GAWK (Chromogranin B), showed a much greater degree of
      variability in all three cases. This study shows promise for plasma 5-HIAA as a
      useful marker for monitoring carcinoid disease. The limitations of blood
      serotonin expressed to the platelet count are highlighted.

PMID- 17456302
TI  - Hypokalaemic rhabdomyolysis.
AB  - Hypokalaemic rhabdomyolysis is unusual, but the association between hypokalaemia
      and rhabdomyolysis can be overlooked if intracellular potassium leakage
      normalizes serum potassium by the time of presentation. This report describes a
      patient who presented with severe pain due to non-traumatic rhabdomyolysis and
      was found to have serum potassium of 1.4 mmol/L; magnesium 0.40 mmol/L; phosphate
      1.40 mmol/L; adjusted calcium 1.87 mmol/L and creatine kinase 6421 U/L. In this
      case, intervention occurred before rhabdomyolysis could progress to the stage at
      which serum potassium may have self-corrected. This patient's hypokalaemia was at
      first refractory to treatment with potassium chloride, possibly due to coexisting
      magnesium deficiency. Initially, the patient denied alcohol abuse, but later
      admitted alcohol misuse prior to withdrawal three days before presentation.
      Hypokalaemia is associated with alcohol misuse, but abrupt withdrawal may
      exacerbate hypokalaemia and hypomagnesaemia. Acute or chronic myopathy is common
      in alcoholics due to alcohol toxicity and paradoxically the risk of
      rhabdomyolysis may be increased during periods of abrupt alcohol withdrawal.

PMID- 17456303
TI  - Quartz renal calculi: were we being led up the garden path?
AB  - Quartz stones are often considered to be of non-human origin or factitious,
      although in some cases, they may have a biological aetiology. X-ray diffraction
      (XRD) spectroscopy was used to analyse fragmented renal stones from a 61-year-old
      lady who presented with bilateral nephrocalcinosis. Analysis of the calculi from
      the left kidney showed a mixed composition: 50% calcium oxalate monohydrate and
      50% quartz. This case highlights the usefulness of XRD in the differentiation of
      authentic from possibly factitious renal calculi.

PMID- 17456304
TI  - Detection of Actrapid by insulin assays.

PMID- 17456305
TI  - Urine free cortisol analysis by automated immunoassay and high-performance liquid
      chromatography for the investigation of Cushing's syndrome: a comment on the
      paper of Ching et al.

PMID- 17456307
TI  - [Distribution and characteristics of hepatitis B virus genotypes in Uighur
      patients with chronic hepatitis B in Xinjiang province of China].
AB  - OBJECTIVE: To study genotype distribution and the characteristics of hepatitis B
      virus (HBV) in Uighur patients with chronic hepatitis B (CHB) in Xinjiang, China.
      METHODS: Type specific primers and PCR were used to detect the HBV genotypes of
      127 Uighur CHB patients in Xinjiang. Genotyping results were confirmed by PCR
      product sequencing. RESULTS: Among the 127 patients, the proportions of genotype
      D, B, C and B/D, C/D, B/C/D were 39.4% (50/127), 22.0% (28/127), 16.5% (21/127)
      and 9.4% (12/127), 8.7% (11/127) and 3.9% (5/127), respectively. The distribution
      of the HBV genotypes showed no significant differences between male and female
      patients (x2 = 8.058, P > 0.05), between HBeAg positive and negative patients (x2
      = 6.033, P > 0.05), and between patients of different ages (x2 = 3.137, P >
      0.05). CONCLUSION: Genotype D HBV is predominant in Uighur patients with chronic
      hepatitis B in Xinjiang. The distribution of various HBV genotypes shows no
      significant differences between these Uighur patients with different HBeAg
      positivity, sex and age.

PMID- 17456308
TI  - [The effect of Ginkgo biloba extract on portal hypertension and hepatic
      microcirculation in rats].
AB  - OBJECTIVE: To evaluate the effect of Ginkgo biloba extract (EGb) on hepatic
      microcirculation and portal hypertension in CCl4 treated rats. METHODS: Twenty
      five male Wistar rats were divided into a blank, a CCl4 treated and a CCl4 plus
      EGb treated group, and all were treated for 10 weeks. The free portal vein
      pressures were measured through catheterizations. Hepatic sinusoidal endothelial
      cells and other parameters of hepatic microcirculation were studied with
      transmission electron microscopy. The amounts of malondialdehyde (MDA),
      endothelin (ET-1), platelet-activating factor (PAF), nitric oxide (NO), cNOS and
      iNOS in the liver tissues were determined. RESULTS: The portal vein pressure of
      the CCl4 plus EGb treated group was (7.4 +/- 0.6) mm Hg while the pressure of the
      CCl4 treated group was (8.7 +/- 0.8) mm Hg. Aggregation of blood cells or
      microthrombosis in hepatic sinusoids, deposition of collagen in hepatic sinusoids
      and spaces of Disse, injury of endothelial cells and capillarization of hepatic
      sinusoid were significantly milder in the EGb group. The amounts of MDA, ET-1,
      PAF, NO and iNOS were markedly lower in the CCl4 plus EGb treated group than in
      the CCl4 treated group. CONCLUSION: The results demonstrated that EGb can
      decrease the portal vein pressure and improve hepatic microcirculation in CCl4
      treated rats. The mechanisms of this effect may involve its inhibition on ET-1,
      PAF, lipid peroxidation, and down regulation of the hepatic iNOS and NO
      expressions.

PMID- 17456309
TI  - [An ultrasonic scoring system for assessing the severity of hepatic fibrosis in
      patients with chronic hepatitis B].
AB  - OBJECTIVE: To discuss the diagnostic value of an ultrasonic assessing system for
      detecting the severity of hepatic fibrosis in patients with chronic hepatitis B
      (CHB). METHODS: Ultrasonographic variables were analyzed in 110 CHB patients. An
      ultrasonic semi-quantitative scoring system using seven ultrasonic morphologic
      parameters, a Fisher discriminating function and three quantitative ultrasonic
      parameters was developed. The performance of these methods was also studied and
      compared. RESULTS: The areas under the curve of the scoring system for different
      liver fibrosis stages were >or= S2: 0.946, >or= S3: 0.914, and S4: 0.915. The
      total score was well correlated with the histological stage of fibrosis (r=0.824,
      P < 0.001). There was a significant difference between the stages of fibrosis.
      The accuracy of the Fisher discriminating function for identifying three study
      endpoints was 76.5%, 78.2% and 67.3%. Combining the ultrasonic scoring system and
      the discriminating function, the specificity was 85%-90% and the accuracy was 77%
      84%. CONCLUSION: Our ultrasonic semi-quantitative scoring system is a noninvasive
      method for quantitating liver fibrosis. If it is used together with a
      discriminating function, the accuracy of diagnosing liver fibrosis can be
      significantly increased.

PMID- 17456310
TI  - [Ultrastructural changes of duodenal mucosas and their significance in patients
      with liver cirrhosis].
AB  - OBJECTIVE: To investigate the ultrastructural changes of duodenal mucosas and
      their significance in patients with liver cirrhosis (PLC). METHODS: Endoscopic
      biopsy duodenal mucosa specimens of 60 PLC and 18 healthy volunteers as controls
      were obtained. Ultrastructural changes of them were studied with transmission
      electron microscopy. These PLC were divided into groups A, B and C according to
      the Child-Pugh classification. The ultrastructural changes in the duodenal
      mucosas of each group were rated and compared with those of the other groups. PLC
      with and without ultrastructural changes of duodenal mucosas were divided into a
      positive group and a negative group. Levels of plasma Alb, TBil, PT, plasma
      endotoxin, and blood ammonia of the PLC were detected and compared. RESULTS:
      There were 20 PLC each in groups A, B, and C. Ultrastructural changes of duodenal
      mucosas were found in 5 PLC of group A, 9 in group B and 17 in group C. Among the
      60 PLC, 52% had some changes in their duodenal mucosas. The changes included
      decrease and rupture of the microvilli; also karyopyknosis, karyorrhexis,
      widening of the gaps of the tight junction and tumefactions of mitochodrion of
      duodenal mucosa epithelial cells. No ultrastructural changes of duodenal mucosas
      were found in the control group. The rate of changes in the three Child-Pugh
      class groups and in the control group were 25%, 45%, 85%, 0% respectively (P <
      0.01). The level of Alb of the positive group was significantly lower than that
      of the negative group (P < 0.01). Levels of plasma TBil, PT, endotoxin and blood
      ammonia of the positive group were significantly higher or longer than those of
      the negative group (P < 0.01). Levels of plasma Alb of the positive and negative
      groups were significantly lower than those of the control group (P < 0.01).
      Levels of TBil, PT, plasma endotoxin and blood ammonia of the positive and
      negative groups were significantly higher or longer than those of the control
      group (P < 0.01). CONCLUSION: There were ultrastructural changes of duodenal
      mucosas in PLC, especially in end-stage PLC. Ultrastructural changes of
      intestinal mucosas in the PLC may have important pathophysiological and clinical
      significance.

PMID- 17456311
TI  - [The relationship between TGFbeta1 and TIMP-1 and its effects on the diagnosis of
      hepatic fibrosis].
AB  - OBJECTIVE: To detect the expressions of serum transforming growth factor beta
      (TGFbeta1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in patients with
      chronic hepatitis B (CHB) in different phases of their liver fibrosis and to
      investigate the effects of TGFbeta1 and TIMP-1 on the diagnosis of hepatic
      fibrosis and the relationship between them. METHODS: Serum TGFbeta1 and TIMP-1
      were detected by enzyme-linked immunosorbent assay and serum HA, LN, PIIINP were
      detected by radioimmunoassay in 40 CHB patients and 12 healthy persons. Liver
      biopsies were performed on the 40 patients. The relationships between the
      TGFbeta1 and TIMP-1 and hepatic fibrosis stages, hepatitis grades and the
      relevance of the five serum makers of the patients were analyzed. RESULTS: Serum
      TGFbeta1, TIMP-1 rose in the early stage of liver fibrosis and their
      sensitivities were higher than that of HA, LN and PIIINP. Serum levels of
      TGFbeta1 and TIMP-1 increased significantly with the development of fibrosis and
      had positive correlations with other fibrotic makers such as HA, LN and PIIINP.
      CONCLUSION: TGFbeta1 and TIMP-1 are involved in the course of developing hepatic
      fibrosis and TIMP-1 may be regulated by TGFbeta1. Both of them can be used as
      diagnostic markers of early hepatic fibrosis.

PMID- 17456312
TI  - [Different expressions of chemokine receptors in human hepatocellular carcinoma
      cell lines with different metastatic potentials].
AB  - OBJECTIVE: To compare different expression profiles of all known chemokine
      receptors in human hepatocellular carcinoma (HCC) cell lines with different
      metastasis potentials. METHODS: Eighteen pairs of chemokine receptor primers were
      designed using Premier software. Expression profiles of the 18 chemokine
      receptors on four HCC cell lines of lower to higher potentials of metastasis
      (SMMC-7721, MHCC97-L, MHCC97-H and HCCLM6) were analyzed by RT-PCR. Expression of
      CXCR4 was detected by RT-PCR. RESULTS: Expression profiles of chemokine receptors
      on four HCC cell lines with different metastatic potentials had significant
      differences (P < 0.01), in which CCR10, CXCR4 and CXCR6 expressions decreased
      gradually as the metastatic potential of the cell lines increased. The
      expressions of CCR3, CCR4, CCR10, CCR12 and XCR1 on HCCLM6 were significantly
      reduced compared with SMMC-7721 (P < 0.01), whereas the expressions of CXCR1 (P =
      0.006) and CXCR5 (P = 0.003) exceeded that of SMMC-7721. Except for CXCR2, CXCR6
      and XCR1, most of chemokine receptors on MHCC97-H were expressed differently
      compared with MHCC97-L (P < 0.05), in which expressions of CCR1 (P = 0.002), CCR2
      (P = 0.004) and CCR5 (P = 0.046) exceeded MHCC97-L. CXCR4 was detected only on
      the positive controls and SMMC-7721 when the template of total RNA was reduced
      one-half in RT-PCR. CONCLUSION: Chemokine receptors are expressed very
      differently at mRNA level on HCC cell lines with different metastatic potentials.
      The different profiles of chemokine receptors in tumor microenvironment and the
      function of CXCR4 in HCC should be further studied. Our findings have important
      implications in understanding the relationship between chemokine receptors and
      the metastatic potential of HCC.

PMID- 17456313
TI  - [The frequency, phenotypes and functions of CD4+ CD25+ regulatory T cells in
      hepatocellular carcinoma patients].
AB  - OBJECTIVES: (1) To evaluate the prevalence, phenotypes and suppressive function
      of CD4+CD25+ regulatory T cells (Tregs) among the in peripheral blood mononuclear
      cells (PBMCs) and tumor-infiltration lymphocytes (TILs) from hepatocellular
      carcinoma (HCC) patients and patients with chronic hepatitis B. (2) To
      investigate the correlation between the frequency of CD4+CD25+ Tregs and clinical
      characteristics of HCC patients. METHODS: PBMCs and TILs in 18 HCC patients, 10
      chronic hepatitis B (CHB) patients and 15 healthy donors were evaluated for the
      phenotypes of CD4+CD25+ Tregs and the proportion of CD4+CD25+ Tregs as a
      percentage of the total CD4+ cells, by flow cytometric analysis with three or
      four color staining. The relationship between the frequency of CD4+CD25+ Tregs
      and tumor TNM stages was analyzed. The CD4+CD25+ Tregs and CD4+CD25- T cells were
      isolated from PBMC of HCC patients and donors. The suppressive function of
      CD4+CD25+ Tregs was analyzed. RESULTS: The percentages of CD4+CD25+ Tregs of the
      HCC patients (6.38% +/- 6.30%) and CHB patients (4.29% +/- 1.82%) were
      significantly higher than those of the healthy donors (1.58% +/- 0.55%, P less
      than 0.01). Among the TILs, the percentage of CD4+CD25+ Tregs was higher (t =
      4.39, P < 0.01). There were significant differences in the prevalence of
      CD4+CD25+ Tregs in early and advanced stage HCCs (stage II vs. III, P less than
      0.05; stage II vs. IV P < 0.01). The proliferative capacity of CD4+CD25- T cells
      was inhibited by the presence of CD4+CD25+ T cells in a dose-dependent manner
      where the level of suppression was correlated to the ratio of the two-cell
      populations. CONCLUSION: These results suggest that the increase in frequency of
      CD4+CD25+ Tregs might play a role in the suppression of the immune response
      against HCC, which may contribute to the HCC cells that escaped from
      immunological surveillance.

PMID- 17456314
TI  - [The efficacy of intravessel obstructive therapy in primary liver cancer patients
      complicated with intrahepatic arteriovenous fistula].
AB  - OBJECTIVES: To investigate the efficacy of interventional obstructive therapy for
      patients with liver cancer complicated with intrahepatic arteriovenous fistula.
      METHODS: Forty-eight of 56 patients with liver cancer complicated with
      intrahepatic arteriovenous fistula, confirmed by angiography, were treated with
      interventional obstructive therapy. The manifestations of the angiography,
      abdominal distention, ascites, and 24 hour urine output of the patients were
      retrospectively analyzed. RESULTS: (1) The arteriovenous fistula connected with
      the main branches of hepatic artery were embolized effectively by interventional
      method. (2) After the treatment, the abdominal distention alleviated remarkably
      (x2 =13.59, P < 0.01), the amount of ascites decreased, 24 hour urine output
      increased significantly (t = 13.57, P < 0.01) and quality of life improved. (3)
      The lifespan of the treated patients was prolonged after the embolization
      therapy. CONCLUSION: Interventional embolization is an effective palliative
      therapy for patients with liver cancer complicated with severe ascites and
      intrahepatic arteriovenous fistula. The good results of this therapy were
      associated with its effect in decreasing portal hypertension of the patients.

PMID- 17456315
TI  - [A study of CXCR4/SDF-1 in hepatocellular carcinoma and liver cirrhosis].
AB  - OBJECTIVE: To investigate the expressions of stromal cell-derived factor-1 (SDF
      1) and CX chemokine receptor-4 (CXCR-4) in patients with hepatocellular carcinoma
      (HC) and liver cirrhosis. METHODS: Peripheral blood and/or ascites fluid were
      collected from 39 hepatocellular carcinoma patients, 16 patients with liver
      cirrhosis, 12 with hepatitis and 12 healthy donors. The SDF-1 expression was
      assayed by ELISA and CXCR-4 was measured by immunohistochemical methods. RESULTS:
      The level of SDF-1 expression in the carcinoma patients was higher than that of
      the liver cirrhosis, hepatitis patients and healthy donors, but there was no
      significant difference between those of the healthy donors and hepatitis patients
      or liver cirrhosis patients. The levels of CXCR-4 expression were closely related
      to the tumor differentiation. CONCLUSION: The expression of SDF-1 in the
      peripheral blood and the CXCR4 expression in the HCC tissues of the HC patients
      may be regarded as markers of HC and they may have a positive relationship with
      the differentiation and metastasis of HC.

PMID- 17456316
TI  - [The presence and the significance of CD4+CD25+ regulatory T cells in livers of
      patients with hepatocellular carcinoma].
AB  - OBJECTIVE: To study the presence and clinical significance of CD4+CD25+
      regulatory T cells in liver tissues of hepatocellular carcinoma (HCC) patients.
      METHODS: CD4+CD25+ regulatory T cells and CD8+ cells and their relative
      proportions in liver tissues and peripheral blood of HCC patients and of healthy
      volunteers were analyzed using flow cytometry. The distributions of CD4+CD25+
      regulatory T cells in liver tissues were also analyzed. RESULTS: Around the tumor
      tissues (peri-tumor), the percentage of CD4+CD25+ regulatory T cells was 10.8% +/
      2.3%, which was obviously higher than in the tissues away from the cancer
      tissues (P < 0.05). The percentage of CD4+CD25+ regulatory T cells in the
      peripheral blood of HCC patients was 9.4% +/- 1.0%, which was obviously lower
      than that of the healthy volunteers (12.9% +/- 1.3%) (P < 0.01). With increasing
      CD4+CD25+ regulatory T cells in the peri-tumor tissue, there was a trend of CD8+
      cells decreasing. CONCLUSION: CD4+CD25+ regulatory T cells played an anti-tumor
      immunity role in hepatocellular carcinoma by restraining the CD8+ cells.

PMID- 17456317
TI  - [The significance of anti-soluble liver antigen/liver-pancreas in diagnosing and
      typing autoimmune hepatitis].
AB  - OBJECTIVE: To study the significance of anti-soluble liver antigen/liver-pancreas
      (anti-SLA/LP) in diagnosing and typing autoimmune hepatitis (AIH). METHODS: Six
      thousand patients with abnormal liver functions, who had their autoantibodies
      checked by immunofluorescent assay (IFA) and immune blotting assay, were reviewed
      retrospectively. RESULTS: Of these 6000 patients with liver diseases, 84 were
      diagnosed AIH. Eighteen patients, 0.3% of the 6000, patients with abnormal liver
      functions, were SLA/LP antibody positive, of which 17 were with AIH-III [2/17
      with AIH /primary biliary cirrhosis (PBC) overlap syndrome], and 1 with chronic
      hepatitis B. Sensitivity and specificity of SLA/LP antibody in diagnosing AIH
      were 20.2% and 99.7% respectively, and the positive prediction value was 94.44%.
      The antinuclear antibody (ANA) titer in the AIH-III group was significantly lower
      than that of the AIH-I group (P < 0.05). The age of patients with anti-SLA/LP was
      higher (58.8% were over 50 years old) than those without this antibody (52.2%
      were 30 to 50 years old). There were no significant differences between the type
      III and type I AIH regarding gender, age, abnormal degree of liver function, PTA,
      IgG, liver cirrhosis rates and response to immunosuppressive therapy. CONCLUSION:
      Anti-SLA/LP is highly specific for diagnosing AIH. Comparing the clinical data of
      type III and type I AIH, we did not find significant differences between the two
      groups.

PMID- 17456318
TI  - [Construction of recombinant plasmid human imprinted gene PEG10 and the primary
      functional identification in transfected cell lines].
AB  - OBJECTIVE: To construct a plasmid expressing human imprinted gene PEG10 and to
      study the effect of overexpression of PEG10 in a stable transfected human normal
      liver cell line L02 and in non-liver derived cell line 293. METHODS: Full length
      cDNA of PEG10 open reading frame 1 was amplified and subcloned into a mammalian
      expression vector pcDNA3.1hisC. Recombinant plasmid was stably transfected into
      L02 cells and control cells via Lipofectamine 2000. The expression and the
      function of PEG10 in L02 cells and control group cells were examined using RT
      PCR, Western blot, MTT and TUNEL. RESULTS: Recombinant plasmid was successfully
      constructed and confirmed through DNA sequencing and restriction digesting. PEG10
      gene accelerated the growth of L02 cells and inhibited their apoptosis but it had
      no conspicuous effect on the non-liver derived cells. CONCLUSION: The constructed
      expressing vector pcDNA3.1hisC-PEG10 provides a useful tool for further study on
      the effects and mechanisms of PEG10. Over-expression of PEG10 may promote L02
      cells' proliferation and inhibit their apoptosis, but not in the non-liver
      derived cell line 293.

PMID- 17456319
TI  - [A clinical analysis of intrahepatic cholestasis of pregnancy in 1241 cases].
AB  - OBJECTIVE: To study the clinical features and diagnosis of intrahepatic
      cholestasis of pregnancy (ICP). METHODS: During the last 10 years 1241 cases of
      ICP stayed in our hospital. Their clinical data were retrospectively reviewed.
      RESULTS: 5.2% of all the maternity patients had ICP. It occurred more in winter
      and 3.5% of ICP occurred in multiple pregnancies. The recurrence rate of ICP was
      30.2%. On the average, it occurred at gestational week 32.6. Skin pruritus was
      the characteristic manifestation and the presenting symptom in 1201 patients
      (96.8%). The other presenting features included elevated serum ALT and AST
      (2.3%), jaundice (8 patients), diarrhea (3 patients), deep yellow urine (2
      patients) and right upper abdominal pain (1 patient). The serum transaminases
      levels were elevated, of which 60% were between 50-200 IU/L. Serum total bile
      acid (TBA) levels were elevated in 82.4% of the patients and bilirubin levels in
      33.4%. The elevated bilirubin levels were 30 to 90 micromol/L in 85% of those
      patients with this condition, and it was never higher than 170 micromol/L.
      CONCLUSION: The basic diagnostic points of ICP are pruritus and abnormal liver
      function characterized by increased transaminases and TBA. Therefore paying
      attention to typical pruritus and other atypical features such as elevated serum
      transaminases, jaundice, diarrhea, deep yellow urine and right upper abdominal
      pain during antenatal care is important for an early diagnosis of ICP.

PMID- 17456320
TI  - [Screening up-regulated genes in hepatic stellate cells treated with PDGF-BB
      using suppression subtractive hybridization technique].
AB  - OBJECTIVE: To construct a subtractive cDNAs library of up-regulated genes in rat
      hepatic stellate cells (HSCs) stimulated with platelet-derived growth factor
      (PDGF)-BB by suppression subtractive hybridization (SSH) technique, to clone the
      up-regulated genes associated with its regulation effects, and to elucidate the
      mechanism of the molecular biology of hepatic fibrosis involved in PDGF-BB.
      METHODS: The mRNA was isolated from HSCs stimulated with PDGF-BB and controlled
      with identical cells untreated with PDGF-BB, and then the cDNAs were synthesized.
      The cDNAs were designated as tester and driver. After being digested by
      restriction enzyme Rsa I, small-sized cDNAs were obtained. Tester cDNA was then
      divided into two groups and ligated to the specific adaptor 1 and adaptor 2,
      individually. After tester cDNA was hybridized with driver cDNA twice and
      underwent two times of nested PCR, the amplified cDNA fragments were subcloned
      into pGEM-Teasy vectors to set up the subtractive library. Amplification of the
      library was carried out with E. coli strain DH5alpha. The cDNA was sequenced and
      analyzed in GenBank with Blast search after PCR. RESULTS: The subtractive cDNAs
      library of up-regulated genes in HSCs stimulated with PDGF-BB was constructed
      successfully. The amplified library contained 102 positive clones. Colony PCR
      showed that 93 clones contained 200-1000 bp inserts. Sequence analysis was
      performed in 31 clones randomly, and the full length sequences were obtained with
      bioinformatics method and searched for homologous DNA sequence from GenBank;
      altogether 13 coding sequences were obtained, which were known ones. The genes
      mainly included voltage-dependent anion channel (VDAC), heat shock protein 47 and
      RAN-member RAS oncogene family genes. CONCLUSION: Acting as one of the most
      effective mitogens, PDGF-BB up-regulated some gene expressions during stimulation
      of the HSCs, including some cell growth associated proteins, some proteins
      participating in intracellular metabolism and some molecular chaperone proteins.
      This work brings some new clues for studying the molecular biological mechanism
      involved in the up-regulated genes in PDGF-BB transactivated HSCs in hepatic
      fibrosis.

PMID- 17456321
TI  - [Screening of serum biomarkers in hepatocellular carcinoma by SELDI technique: a
      preliminary study].

PMID- 17456322
TI  - [Priming of HBV antigen-specific cytotoxic T cell response using uric acid
      treated dendritic cells in mice].

PMID- 17456323
TI  - [The relationship between the expression of TR6 mRNA and protein in the apoptosis
      of hepatocellular carcinoma cells].

PMID- 17456324
TI  - [Changes of gene expressions in patients with hepatocellular carcinoma].

PMID- 17456325
TI  - [Preparation of monoclonal antibodies against recombinant keratinocyte growth
      factor variants].

PMID- 17456326
TI  - [Study of inhibitory effects of Gankang suppository on hepatitis B virus and its
      impact on serologic biochemistry in ducklings].

PMID- 17456327
TI  - [An effective method of isolating and culturing human hepatic stellate cells].

PMID- 17456328
TI  - [A study on health-related quality of life in patients with hepatitis B virus
      related liver cirrhosis].

PMID- 17456329
TI  - [A clinical study of consensus interferon alpha treatment in chronic hepatitis B
      virus-infected patients].

PMID- 17456330
TI  - [The relationship between adiponectin and nonalcoholic fatty liver disease in
      infant rabbits fed a fat-rich diet].

PMID- 17456332
TI  - [Pay attention to community acquired pneumonia in children].

PMID- 17456331
TI  - [Advances in research of hepatitis B virus resistance to adefovir].

PMID- 17456333
TI  - [Guidelines for management of childhood community acquired pneumonia (for trial
      implementation) (I)].

PMID- 17456334
TI  - [Human parainfluenza virus infections in infants and young children with acute
      respiratory infections in Beijing].
AB  - OBJECTIVE: To understand the impact of human parainfluenza virus (HPIV) on acute
      respiratory infections in infants and young children in Beijing. METHODS:
      Multiplex reverse transcription-PCR was used to amplify the hemagglutinin (HA)
      gene fragment of HPIV from clinical specimens. Primer pairs derived from a
      conserved region of the HA genes of HPIV were used to develop the multiplex RT
      PCR for detecting and typing HPIV. The sensitivity and specificity of the method
      were determined by using various RNA and DNA viruses as controls. Specimens
      collected from 3519 children with acute respiratory infections from Aug. 2003 to
      Apr. 2006 were analyzed for HPIV by the multiplex RT-PCR as well as for other
      respiratory viruses by virus isolation and/or indirect immunofluorescent assay
      (IFA). Ten amplicons with expected molecular weight matching different types of
      HPIV were randomly selected for sequence analysis. RESULTS: Only the cDNA from
      the isolated strains of HPIV 1 and 3 was positive by the multiplex RT-PCR.
      Phylogenetic analysis for those 10 amplicons' sequences which belong to HPIV 1 -
      4 types respectively as determined by multiplex-PCR indicated that these
      specimens were truly HPIV positive. These 10 HPIV positive specimens included two
      specimens of type 4 which was further subtyped as HPIV4A and 4B by sequence
      analysis. With the multiplex RT-PCR, HPIV were detected in 349 out of 3519
      specimens with the positive rate of 9.9% (349/3519), which is higher than 4.8% by
      the methods of virus isolation and/or IFA. And the HPIV positive rates were high
      in patients with not only acute upper but also lower respiratory tract infection.
      No regular seasonality distribution of HPIV infection was found. HPIV 1 and 3
      were more common than HPIV 2 and 4. CONCLUSION: With higher sensitivity and
      specificity than virus isolation and IFA, multiplex RT-PCR is beneficial for the
      etiologic and epidemiologic studies on HPIV, as well as for HPIV typing. The data
      from this study indicate that HPIV is one of the important etiological viruses of
      acute respiratory tract infections in infants and young children in Beijing.

PMID- 17456335
TI  - [Analysis of 53 cases with bronchoscopically confirmed pediatric
      tracheobronchomalacia].
AB  - OBJECTIVE: Tracheobronchomalacia is one of the common respiratory tract dysplasia
      in children. Its symptoms are nonspecific, and routine methods are unreliable in
      the assessment of tracheobronchomalacia in children. In addition, many physicians
      are confused about its clinical characteristics, so tracheobronchomalacia is
      often underdiagnosed. The purpose of this study was to explore the clinical
      features of tracheobronchomalacia in children and to investigate the diagnostic
      value of flexible bronchoscopy for children with tracheobronchomalacia. METHOD:
      For diagnosis and treatment, 229 children out of 4725 patients hospitalized in
      the division of respiratory disorders were examined by Olympus BF3c-20 flexible
      bronchoscopy or by Olympus BF-P20 flexible bronchoscopy under general anesthesia
      with propofol, in Chongqing Children's Hosptial from April 2004 to April 2006.
      Fifty-three cases were confirmed to have tracheobronchomalacia by bronchoscopy,
      patients' data including airway lesion, age, sex, clinical characteristics, aided
      examinations, treatment, final outcomes, were collected and analyzed. RESULTS:
      (1) Of the 53 children with tracheobronchomalacia, 31 were not suspected for this
      diagnosis prior to bronchoscopy, who were instead misdiagnosed as refractory
      pneumonia, difficult-to-control asthma, bronchial foreign body, bronchopulmonary
      dysplasia and pulmonary atelectasis of unknown origin or bronchiolitis. (2) In
      the 53 children with tracheobronchomalacia aged one month to eight years, 41 were
      infants, 6 were younger than two years, 4 were younger than 3 years and the rest
      2 cases were older than 3 years. The risk of tracheobronchomalacia related
      inversely with ages. Ten cases were girls and 43 were boys. (3) Eleven cases had
      tracheomalacia, 24 bronchomalacia, 18 tracheobronchomalacia; 12 cases had malacia
      on left lung, 11 on right lung, 19 on both sides; 21 children were mild cases, 25
      moderate cases, 7 severe cases. (4) In the 53 children with
      tracheobronchomalacia, 28 had recurrent or prolonged wheezing, 16 chronic cough,
      5 recurrent respiratory infections, 2 atelectasis of unknown origin, and 2
      dyspnea. CONCLUSIONS: The infants and toddlers seem to be predisposed more to the
      bronchomalacia than the older children. Clinical features of children with airway
      malacia were variable and atypical, expiratory stridor and cough are the most
      commonly reported symptoms. Flexible bronchoscopy should be regarded as a "golden
      standard" method for diagnosing TBM.

PMID- 17456336
TI  - [Association of interleukin 8 single nucleotide polymorphisms with the
      susceptibility to respiratory syncytial virus infection].
AB  - OBJECTIVE: To explore the association of interleukin 8 (IL-8)-251T/A and 781 C/T
      single nucleotide polymorphisms (SNPs) with the susceptibility of infants and
      young children to respiratory syncytial virus (RSV) infection. METHOD: This study
      included 101 hospitalized patients under 2 years of age who suffered from RSV
      pneumonia, 108 hospitalized patients under 2 years of age with non-RSV pneumonia
      and 35 core families with a child hospitalized for RSV pneumonia. Genotypes of 2
      SNP loci in all enrolled persons were defined by allele specific polymerase chain
      reaction (AS-PCR), and confirmed by gene sequencing. The allele's frequencies of
      SNPs were analyzed with case-control study and transmission disequilibrium test
      (TDT), linkage of 2 loci and haplotypes composed of the 2 loci were also studied.
      RESULTS: (1) The frequency of IL-8-251T in cases was dramatically high (OR =
      2.08, P = 0.0002, case-control study; LRT = 14.31, P = 0.0008, TDT). (2) IL-8
      251T and 781C was linkaged (D' = 0.607 +/- 0.03, r(2) = 0.2861, P = 0.0000). (3)
      Haplotype of TC was significantly high in cases (P = 0.01). CONCLUSION: These
      findings support that haplotype of TC composed of IL-8-251T and 781C is
      associated with the susceptibility to RSV, namely, some RSV predisposing genes
      are located in the gene fragment including TC haplotype or linked tightly with
      this gene fragment.

PMID- 17456337
TI  - [Association of CD14 gene polymorphism with atopic diseases in Chinese Han ethnic
      group children].
AB  - OBJECTIVE: To investigate the distribution characteristics of the single
      nucleotide polymorphisms (SNPs) of the human CD14 gene in Chinese Han ethnic
      group children in Wenzhou, and their association with atopic diseases. METHODS:
      Totally 113 cases were recruited in atopic disease group who met the following
      criteria: 2 - 12 years old, clinically diagnosed as asthma or allergic rhinitis
      or atopic dermatitis, elevation of serum total IgE levels and serum specific IgE.
      Sixty-seven healthy children were enrolled in control group. The related regions
      of CD14 gene were sequenced to identify and characterize the SNPs, and plasma
      TIgE and SIgE were detected by immunoassay system and uniCAP system,
      respectively. The frequency of genotypes and alleles between two groups, as well
      as the levels of IgE in different genotypes, were compared. RESULTS: CD14/-159
      SNP was present in Han ethnic group population of Wenzhou. The frequency of each
      genotype was 57.0% (TT), 28.0% (TC), 15.0% (CC) in normal children, and 46.9%
      (TT), 35.4% (TC), 17.7% (CC) in atopic children. No significant difference was
      found in the distribution of CD14/-159 polymorphism between atopic children and
      healthy control (chi(2) = 1.918, P > 0.05) according to Hardy-Weinberg principle
      statistics. There were no significant difference in frequency of each genotype
      between boys and girls. No significant difference was found in the total plasma
      IgE levels among groups of TT genotypes [(2520 +/- 460) IU/L], TC genotypes
      [(2400 +/- 460) IU/L] and CC genotype [(2500 +/- 460) IU/L] (F = 0.807, P >
      0.05). CONCLUSION: CD14/-159 SNP is present in Han ethnic group children in
      Wenzhou, and other SNP in CD14 gene was not found. TT genotype was the primary
      genotype in CD14/-159 SNP in the children studied. No relationship between CD14/
      159 SNP and atopic disease or serum total IgE level was found.

PMID- 17456338
TI  - [Clinical and polyneuroelectrophysiological characteristics of infantile spasm].
AB  - OBJECTIVE: To explore the characteristics of various seizure types in infantile
      spasm (IS) and to recognize the clinical and electrophysiological differences
      among spasm, myoclonic and tonic seizures. METHODS: Totally 681 seizures of 8
      infants with IS were analyzed, including 20 episodes of non-cortical myoclonus
      which were finally ruled out by video-electroencephalogram-electromyogram
      polygraphic recordings (VEEG-EMG) and off-line analysis of jerk-locked back
      averaging (JLA). As a control, the data of 58 myoclonic seizures collected from
      an infant with Aicardi syndrome within two months before his typical clinical
      presentations of IS were also analyzed. RESULTS: Three types of seizures were
      recorded from the 8 infants, including spasm, myoclonic and tonic seizures with
      the incidence of 94.4%, 4.5%, and 1.1%, respectively. Spasms were mostly
      presented as body muscle contraction axially, which often occurred in clusters
      and evolved in a crescendo-decrescendo manner; 85.7% of them lasted for 0.4 - 3.0
      s and 14.3% for 3 - 7 s. In addition, there were 273 seizures which were
      identified as subtle spasms according to their ictal EEG with high voltage slow
      wave (HVS) and fast wave bursts in most. There was no constantly time-locked EEG
      correlating to spasms even when JLA was applied for analysis. Myoclonic seizures
      were shock-like muscle constraction lasting for less than 400 ms with or without
      visible epileptic discharges in its ictal EEG. However, there was a time-locked
      cortical discharge discerned by JLA in epileptic myoclonus. Tonic seizures were
      consisted of sustained muscle contractions involving limbs and trunk, lasting for
      more than 3 s. Its ictal EEGs were more likely low amplitude fast waves and
      medium amplitude theta activities. Some spasms, named as tonic spasm, could be
      distinguished from tonic seizure according to the seizure duration which was
      always less than 2 s in tonic spasms and their different EEG patterns.
      CONCLUSIONS: There were various seizure types in IS but spasm was the predominant
      one. With polyneuroelectrophysiological tests including EEG-EMG and JLA, it would
      be much helpful to precisely recognize the different common seizure types
      including spasm, tonic spasm, myoclonic and tonic seizure during infancy which is
      important for the diagnosis, classification and treatment of infantile epilepsy.

PMID- 17456339
TI  - [Clinical characteristics of cases with leukoencephalopathy with vanishing white
      matter].
AB  - OBJECTIVE: To analyze and review the characteristics of leukoencephalopathy with
      vanishing white matter (VWM). METHODS: The clinical features including clinical
      manifestations, neurologic signs, cranial MRI and laboratory tests in 9 patients
      with the diagnosis of VWM were analyzed and the characteristics of the disease
      were reviewed. RESULTS:  CLINICAL MANIFESTATIONS: 8 cases had symptoms involving
      central nervous system, 1 case only showed abnormal cranial MRI findings. The
      onset of the disease occurred between 6 months to 3 years of age. Family history
      was positive in 5 cases. Almost all cases had normal psychomotor development
      before the onset of the disease. The initial symptom was usually movement
      disorder with predominant involvement of lower limbs. The onset or deterioration
      of the disease was followed by respiratory tract infection in 6 cases and minor
      head trauma preexisted in 3 cases. The course of the disease was progressive in 7
      cases and there was episodic deterioration in 4 cases. Mental abilities were
      relatively better preserved. Head circumference was normal in 7 cases. Positive
      upper motor unit signs were found in 8 cases and ataxia in 4 cases. Bilateral
      optic nerve atrophy was found in 3 cases. Cranial MRI indicated diffuse and
      symmetrical involvement of deep white matter which showed long T(1) and T(2)
      signal. Subcortical white matter was also involved with predominance in frontal
      and parietal lobes. Flair image showed symmetrical high signal intensity in
      cerebral white matter with low signal intensity similar to that of CSF in partial
      area or low signal in most area of white matter with only meshwork of higher
      signal preserved. The results of all the laboratory tests including the enzyme
      and biochemical test specific for some well-known leukoencephalopathy were
      normal. CONCLUSIONS: The clinical features of VWM include: 1. Initial symptom is
      usually movement disorder; 2. Movement disorder is more prominent compared to
      mental retardation; 3. Cranial MRI shows symmetrical abnormal T(1) and T(2)
      signal in deep white matter with signs of vanishing white matter. Exclusion of
      other hereditary and acquired leukoencephalopathy is necessary for diagnosis.
      Final diagnosis should be made on the basis of genetic evidence.

PMID- 17456340
TI  - [Experimental study on the possibility of brain damage induced by chronic
      treatment with phenobarbital, clonazepam, valproic acid and topiramate in
      immature rats].
AB  - OBJECTIVE: To explore the possibility of brain damage induced by several anti
      epileptic drugs (AEDs) at therapeutic level to immature brain of rat. METHODS:
      Totally 160 healthy Spraque-Dawley (SD) rats selected for the study were divided
      into infant and adult groups. Each age group was treated with phenobarbital (PB),
      clonazepam (CZP), valproic acid (VPA), topiramate (TPM) or normal saline
      respectively for 2 or 5 weeks with 8 rats in each group. The steady-state plasma
      concentrations of AEDs at the experimental dosage were coincided with the range
      of clinical therapeutic concentrations. Drug levels in plasma were determined by
      fluorescence polarization. Body and brain weights were measured when the rats
      were sacrificed. Histological studies on the tissues of frontal lobes and
      hippocampus were performed by Nissl staining. And ultrastructural changes of
      brain were observed by the transmission electron microscopy. Plasma neuron
      specific enolase (NSE) was determined by ELISA. Expression of apoptosis-related
      proteins Bcl-2 and Bax in neurons was detected by immunohistochemistry. Neuronal
      apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick
      end labeling (TUNEL). RESULTS: (1) There were no significant differences in brain
      weight among all adults groups. While remarkable reduction of brain weight was
      observed in immature rats exposed to CZP or PB (P < 0.01) for long term. (2)
      Significant neurodegeneration, neuronal necrosis and decrease in the number of
      neurons can be observed in the immature rats exposed to CZP or PB for long
      period. (3) For immature rats, concentration of plasma NSE was increased even
      after short-term treatment with PB [(8.84 +/- 2.10) nmol/L] compared with control
      group [(6.27 +/- 1.27) nmol/L] (P < 0.01). And it was increased in immature rats
      exposed to CZP [(8.15 +/- 1.67) nmol/L] or PB [(8.07 +/- 1.27) nmol/L] for long
      term compared with controls [(6.02 +/- 1.20) nmol/L] (P < 0.01). But there were
      no significant differences between AEDs-treated adult rats and control rats. (4)
      The expression of Bcl-2 and Bax protein in mature brain did not change at
      therapeutic level. In contrast, expression of Bax protein in the frontal lobe was
      increased significantly in immature rats receiving CZP and PB for long period
      compared with control. (5) The number of TUNEL positive cells in immature rats
      exposed to CZP or PB for long term was obviously increased. CONCLUSIONS: PB and
      CZP may result in remarkable histological abnormalities, neuronal apoptosis and
      necrosis in immature brain. The brain damage induced by PB was more serious and
      persistent than that induced by CZP.

PMID- 17456341
TI  - [Gastric epithelial cell proliferation, apoptosis and P53 protein expression in
      children with Helicobacter pylori associated chronic gastritis].
AB  - OBJECTIVE: To investigate whether Helicobacter pylori infection has any effects
      on the epithelial cell proliferation, apoptosis and P53 gene expression as well
      as its role in the pathogenesis of chronic gastritis. METHODS: Sixty children
      with chronic gastritis were studied. All the children underwent upper digestive
      tract endoscopy and biopsy specimens were taken. Helicobacter pylori infection
      was determined with microscopic examination after Gimsa staining and the rapid
      urease test and 30 of the children were Helicobacter pylori positive and the
      other 30 were negative. The relation between the findings and cell proliferation
      was studied by immunostaining; the status of gastric apoptosis was tested by DNA
      fragmentation in situ using TdT-mediated dUTP biotin nick end labeling (TUNEL).
      Immunohistochemical method was used to detect the expression of P53 protein; CagA
      antibody was tested by Western blotting. RESULTS: (1) The proliferative index and
      apoptosis index in children with Helicobacter pylori infection with CagA positive
      gastritis were much higher than those of Helicobacter pylori negative gastritis
      patients [(11.56 +/- 4.21)% vs. (5.85 +/- 2.21)%, (10.58 +/- 5.31)% vs. (2.86 +/-
      0.64)%, P < 0.01]. (2) The proliferative index and apoptosis index in 30 cases
      with Helicobacter pylori infection with CagA positive gastribis were much higher
      than 21 cases who were cured by effective drugs [(11.50 +/- 4.11)% vs. (3.74 +/-
      2.30)%; (10.58 +/- 4.02)% vs. (3.74 +/- 2.30)%, P < 0.01]. (3) The expression of
      P53 protein in Helicobacter pylori with CagA positive gastritis children was much
      higher than that of Helicobacter pylori negative cases [(63% vs 16%), P < 0.1].
      CONCLUSION: CagA positive Helicobacter pylori infection with gastritis improved
      gastric epithelial cell proliferation and apoptosis. The abnormal expression of
      P53 protein in gastric epithelium may play an important role in regulation of the
      processes.

PMID- 17456342
TI  - [Changes and clinical significance of Toll-like receptor 2 and 4 expression in
      neonatal infections].
AB  - OBJECTIVES: Neonates are vulnerable to various infections because of their
      immature immune responses. Toll-like receptors could induce immune responses,
      both the innate and the acquired immune responses. The aim of the present study
      was to investigate the changes of TLR2 and TLR4 in neonatal infections, and to
      determine their roles in anti-infection immune reaction. METHODS: A total of 200
      infants were divided into six groups: sepsis group (n = 21), bacterial pneumonia
      group (n = 70), bacterial meningitis group (n = 17), urinary tract infection
      group (n = 38), congenital syphilis group (n = 11) and non-infection group (n =
      48). The TLR mRNA was determined by RT-PCR. The protein expression of TLR and the
      percentage of TLR positive cells were evaluated through flow cytometric analysis.
      RESULTS: 1. The TLR2 mRNA expression increased significantly in the sepsis group
      (6.14 +/- 0.80), most significantly in the Gram positive sepsis group (6.43 +/-
      0.74). TLR2 mRNA expression was also significantly higher in the bacterial
      pneumonia group (5.49 +/- 0.62), the bacterial meningitis group (5.61 +/- 0.60)
      and the congenital syphilis group (5.89 +/- 0.38). TLR2 protein expression was
      the highest in the sepsis group and significantly increased in the bacterial
      pneumonia group, bacterial meningitis group and the congenital syphilis groups as
      well, all were higher than the TLR2 protein expression of the non-infectious
      group (1.27 +/- 0.75). The TLR2 protein expression in the Gram positive bacterial
      sepsis group was 2.54 +/- 0.68, that of Gram negative bacterial sepsis group was
      1.25 +/- 0.51 (P < 0.05). The percentage of TLR2 positive cells in the neonatal
      infection group was (70.95 +/- 20.15)%, which did not differ significantly from
      that of non-infection group. 2. The mRNA expression of TLR4 was the highest in
      the sepsis group (6.20 +/- 1.59), while that in the Gram negative bacterial
      sepsis group was 6.78 +/- 1.79, higher than that of the Gram positive bacterial
      sepsis group, 5.39 +/- 0.78, (t = 2.29, P = 0.037). TLR4 mRNA expression
      increased significantly in the bacterial pneumonia group (5.33 +/- 1.07), the
      bacterial meningitis group (5.87 +/- 0.70) and the urinary tract infection group
      (5.38 +/- 0.91). There were no significant differences in TLR4 protein expression
      among these groups. The percentage of TLR4 positive cells in the neonatal
      infection groups was (0.71 +/- 0.31)%, higher than that of non- infection group
      (0.29 +/- 0.36)%. 3. In the Gram positive bacterial sepsis group, the mRNA
      expression of TLR2 (6.43 +/- 0.74) was higher than the mRNA expression of TLR4
      (5.39 +/- 0.78), (t = 1.56, P = 0.024). In the Gram negative bacterial sepsis
      group, the mRNA expression of TLR4 (6.78 +/- 0.79) was significantly higher than
      the mRNA expression of TLR2 (5.64 +/- 0.68) (t = 2.63, P = 0.011). In the sepsis
      group, the TLR2 protein expression was significantly higher than the expression
      of TLR4 (t = 1.06, P = 0.044). The percentage of TLR4 positive cells was lower
      than the percentage of TLR2 positive cells among all these groups, P < 0.01. 4.
      Correlation analysis on gestational age and the mRNA expression, the protein
      expression and the percentage of TLR2 and TLR4 positive cells among all these
      groups did not show any statistical significance. CONCLUSIONS: The mRNA and the
      protein expression of TLR2 and the mRNA expression of TLR2 increased
      significantly in the studied neonatal infection groups, especially in the severe
      sepsis groups. The mRNA expression of TLR2 increased mainly in the Gram positive
      bacterial infection groups, and the mRNA expression of TLR4 increased in the Gram
      negative bacterial infection groups, suggesting that both the TLR2 and TLR4
      signal pathway took part in the immune mechanism of neonatal infection, providing
      new idea and experimental basis for further understanding of immune mechanism of
      neonatal infection.

PMID- 17456343
TI  - [Correlation between matrix metalloproteinases activities and myocardial injury
      in neonatal rats after asphyxia].
AB  - OBJECTIVE: To study possible correlation between matrix metalloproteinases (MMPs)
      activities and myocardial injury after asphyxia in neonatal Wistar rats. METHOD:
      Sixty neonatal Wistar rats (7 to 10 days old) were randomly divided into four
      groups: control group (group D); asphyxia groups A, B and C (1 day, 7 days, 14
      days after asphyxia), every group had 15 rats. In the asphyxia groups, animal
      model was produced by normobaric asphyxia. Groups A, B and C were sacrificed on
      days 1, 7 and 14 days after asphyxia, and group D rats were sacrificed on the 7
      th day. Then the heart blood was taken to tested the serum cTnI. The myocardial
      MMPs-3 and 9 activity was measured by using immunohistochemical assay.
      Histological sections of the hearts were stained with hematoxylin-eosin and
      myocardial histopathological scores were determined under an optical microscope.
      The amount of myocardial collagen was measured by means of chloramines T.
      RESULTS: cTnI was significantly higher in group A (0.3680 +/- 0.40 ng/ml) than
      group D (0.0783 +/- 0.06 ng/ml) (P < 0.05), and was lower in group B (0.1889 +/-
      0.15 ng/ml) but still significantly different from that of group D (P < 0.05),
      and declined to the normal level in group C (0.1338 +/- 0.07 ng/ml), but the
      difference between groups C and D was not significant (P > 0.05). Myocardial
      tissue MMPs-3 activity was transiently high in group A (0.1847 +/- 0.04), higher
      in group B (0.2780 +/- 0.05) as compared to group D (0.1213 +/- 0.03) (P < 0.05
      for all). The activity of MMPs-3 increased earlier than that of MMPs-9. The
      amount of myocardial collagen of group B (38.94 +/- 0.67) and C (40.69 +/- 0.75)
      was significantly greater than that of group D (P < 0.05). Myoardial tissue MMPs
      3 and MMPs-9 positively correlated with myocardial histopathological scores (r =
      0.669, 0.667, P < 0.05) and myocardial collagen (r = 0.482, 0.679, P < 0.05).
      CONCLUSIONS: In rats with asphyxia, there was an excess activation of myocardial
      MMPs-3 and MMPs-9 activities and secondary to which, the quantity of myocardial
      collagen increased. The injuries of myocardium may be closely associated with
      myocardial tissue MMPs. MMPs may be used to evaluate the severity of myocardial
      interstitial damage.

PMID- 17456344
TI  - [Acanthopanax Senticosus Saponins induced tolerance to ischemia and its possible
      molecular mechanism in PC12 cells].
AB  - OBJECTIVE: To study the tolerance to ischemia induced by Acanthopanax Senticosus
      Saponins (ASE) in PC12 cells and the involved mechanism. METHODS: An ischemic
      model was developed in PC12 cell line by treatment with oxygen-glucose
      deprivation. The effects of ASE pretreatment on tolerance of PC12 cells to
      ischemia were evaluated by MTT assay and analysis of cellular morphology. The
      expression of hypoxia-inducing factor (HIF)-1alpha, erythropoietin (EPO) after
      the pretreatment with ASE was detected by Western blotting. The DNA binding
      activities of HIF-1 in PC12 cells with the pretreatment of ASE were demonstrated
      by using electrophoretic mobility shift assay (EMSA). RESULTS: In ischemia model,
      the viability of PC12 cells was decreased to (49.12 +/- 3.22)% after oxygen
      glucose deprivation for 9 hours. However, ASE (50 microg/ml) pretreatment could
      remarkably increase the viability of PC12 cells by (67.97 +/- 2.92)%. There were
      significant differences between the experimental group and control group (F =
      473.67, P < 0.01). The cellular morphology showed that PC12 cells exposed for 7
      days to nerve growth factor (NGF) exhibited round, smooth cell bodies with normal
      processes and that processes formed extensive network. At 9 hour after ischemia,
      cell bodies of many PC12 cells were found shrinken, the processes were disrupted
      and network disappeared. However, pretreatment with ASE (50 microg/ml) could
      largely prevent the morphological damage to PC12 cells that would have caused by
      subsequent exposure to 9 h ischemic insult, many cellular bodies were intact and
      many processes and network of PC12 cells still existed. The expression of HIF
      1alpha increased after pretreatment with ASE shown by Western blot. There were
      significant differences between the experimental group and control group (F =
      167.18, P < 0.01). The DNA binding activities of HIF-1 in PC12 cells after
      pretreatment with ASE was significantly increased, and it could activate the
      expression of EPO (F = 128.37, P < 0.01). CONCLUSIONS: The pretreatment with ASE
      could induce tolerance against ischemia in PC12 cells. The elevated expression
      and increased DNA binding activity of HIF-1alpha, the overexpression of its
      downstream target EPO may be the molecular mechanism in tolerance of PC12 cells
      to ischemia induced by ASE pretreatment.

PMID- 17456345
TI  - [Clinical immune responses of low birth weight infants to vaccination against
      hepatitis B].

PMID- 17456346
TI  - [Pseudomonas aerugionsa septicemia in a newborn infant].

PMID- 17456347
TI  - [Methylmalonic acidemia in a neonate].

PMID- 17456349
TI  - [Diagnosis and treatment of Fabry disease].

PMID- 17456348
TI  - [Report of a case with cerebral infarction in Henoch-Schonlein purpura].

PMID- 17456350
TI  - [Variation and drug resistance of HIV in children with HIV-infection/AIDS].

PMID- 17456351
TI  - [Progress in studies on the mechanism of antiviral effects of cytotoxic T
      lymphocytes].

PMID- 17456352
TI  - [Summary of Minutes for the 4th Biennial Scientific Meeting of Asia Pacific
      Pediatric Endocrine Society].

PMID- 17456353
TI  - [Surgical management of meningiomas].

PMID- 17456354
TI  - [The methylation and mRNA expression of SLC5A8 and TMS1/ASC genes in human
      glioma].
AB  - OBJECTIVE: To study the methylation status of the SLC5A8 and TMS1/ASC genes,
      candidate tumor-inhibiting genes closely related to the central nervous system,
      in the promoter regions, the mRNA expression of these 2 genes, and their
      correlation with the clinical characteristics in human glioma. METHODS: The
      methylation status of SLC5A8 and TMS1/ASC genes in the promoter regions was
      studied by methylation specific PCR (MSP) in the specimens of primary astrocytoma
      from 88 patients, 55 males and 33 females, aged 12 - 81, and 10 specimens of
      normal brain tissue, all obtained during operation, and in the human glioma cells
      of the lines U251 and SHG-44. The mRNA expression levels of SLC5A8 and TMS1/ASC
      genes in 30 specimens of primary glioma and 10 specimens of normal brain tissue
      were determined by conventional RT-PCR and real-time PCR. 5-Aza-2'-deoxycytidine
      (5-Aza-CdR), a demethylating agent, was added into the culture fluid of the U251
      and SHG-44 cells, and then real-time PCR was used to the methylation status and
      mRNA expression levels of the SLC5A8 and TMS1/ASC genes. RESULTS: MSP showed that
      the SLC5A8 promoter region was hypermethylated in 62 of the 88 specimens of
      astrocytoma (70.45%) and the TMS1/ASC promoter region was hypermethylated in 51
      of the88 specimens of astrocytoma (57.95%). But no methylation of SLC5A8 and
      TMS1/ASC promoter was detected in the 10 specimens of normal brain tissue. The
      mRNA expression of SLC5A8 gene and the mRNA expression of TMS1/ASC gene in the
      specimens of astrocytoma of different pathological grades were all significantly
      decreased compared to the specimens of normal brain tissue (all P < 0.05). The
      mRNA expression of SLC5A8 gene was not significantly related to the age and sex,
      however, the mRNA expression of TMS1/ASC was significantly higher in the age
      group > 60 than in other age groups (all P < 0.05). Both U251 and SHG-44 glioma
      cells showed methylation of SLC5A8 and TMS1/ASC genes and after the treatment of
      5-Aza-CdR both genes showed reactivated mRNA expression. CONCLUSION:
      Hypermethylation of SLC5A8 and TMS1/ASC genes in the promoter regions may play an
      important role in the down-regulation of their mRNA levels in glioma. The
      methylation frequency and mRNA levels of SLC5A8 or TMS1/ASC genes are closely
      related to the malignant development of glioma.

PMID- 17456355
TI  - [Isolation and identification of brain tumor stem cells from human brain
      neuroepithelial tumors].
AB  - OBJECTIVE: To establish a simplified culture system for the isolation of brain
      tumor stem cells (BTSCs) from the tumors of human neuroepithelial tissue, to
      observe the growth and differentiation pattern of BTSCs, and to investigate their
      expression of the specific markers. METHODS: Twenty-six patients with brain
      neuroepithelial tumors underwent tumor resection. Two pieces of tumor tissues
      were taken from each tumor to be dissociated, triturated into single cells in
      sterile DMEM-F12 medium, and then filtered. The tumor cells were seeded at a
      concentration of 200,000 viable cells per mL into serum-free DMEM-F12 medium
      simply supplemented with B27, human basic fibroblast growth factor (20 microg/L),
      human epidermal growth factor (20 microg /L), insulin (4 U/L), L-glutamine,
      penicillin and streptomycin. After the primary brain tumor spheres (BTSs) were
      generated, they were triturated again and passed in fresh medium. Limiting
      dilution assay was performed to observe the monoclone formation. 5
      bromodeoxyuridine (BrdU) incorporation test was performed to observe the
      proliferation of the BTS. The BTSCs were cultured in mitogen-free DMEM-F12 medium
      supplemented with 10% fetal bovine serum to observe their differentiation.
      Immunocytochemistry was used to examine the expression of CD133 and nestin,
      specific markers of BTSC, and the rate of CD133 positive cells. RESULTS: Only a
      minority of subsets of cells from the tumors of neuroepithelial tissue had the
      capacity to survive, proliferate, and generate free-floating neurosphere-like
      BTSs in the simplified serum-free medium. These cells attached to the poly-L
      lysine coated coverslips in the serum-supplemented medium and differentiated. The
      BTSCs were CD133 and nestin positive. The rate of CD133 positive cells in the
      tumor specimens was (21 +/- 6.2)% - (38 +/- 7.0)%. CONCLUSION: A new simplified
      culture system for the isolation of BTSCs is established. The tumors of human
      neuroepithelial tissue contain CD133 and nestin positive tumor stem cells which
      can be isolated, proliferate and differentiate in vitro and give rise to brain
      tumor spheres. This tumorigenic subset may provide both a platform for brain
      tumor research and a target for clinical treatment.

PMID- 17456356
TI  - [Trans-cranio-naso-orbital approach in treatment of ethmoid sinus malignant
      tumors: analysis of 39 cases].
AB  - OBJECTIVE: To summarize the experience in treatment of ethmoid sinus malignant
      tumors via trans-cranio-naso-orbital approach. Post-operationally follow-up was
      conducted in 27 cases for 3.5 years (3 months to 7 years). METHODS: The clinical
      data of 39 patients with ethmoid sinus malignant tumors, 25 males and 14 females,
      aged 42 (20 - 65), with the chief complaints of nasal airway obstruction,
      rhinorrhagia, nasal neoplasm, exophthalmos, decreased vision, facial numbness,
      disturbance of consciousness, etc, who underwent resection of tumor via trans
      cranio-naso-orbital approach retrospectively. Pre-operational MR showed that the
      tumor invaded the anterior cranial fossa in 38 cases, invading the orbit in 31
      cases, invaded the pterygopalatine fossa in 5 cases, invaded the middle cranial
      fossa and cavernous sinus in 3 cases. RESULTS: Tumor total removal was achieved
      in 32 cases (including removal en bloc in 9 cases), and subtotal removal in 7
      cases. Pathological examination diagnosed 10 cases as with olfactory
      neuroblastoma, 8 cases with adenocarcinoma, 7 cases with squamous cell carcinoma,
      6 cases with pallima carcinoma, 4 cases with unclassified sarcoma, 3 cases with
      undifferentiated carcinoma, and 1 case with schneiderian carcinoma.
      Postoperatively, temporal CSF leak was found in 5 cases. There was no
      intracranial or wound infection. Local recurrence was found in 8 cases, 1 case
      had lung metastasis, and 4 cases died 1 month to 6 years postoperatively.
      CONCLUSION: Adequate exposure of the ethmoid sinus tumor involving the anterior
      cranial fossa and orbit can be obtained via suitable trans-cranio-naso-orbital
      approach, and by this approach the tumor can be removed en bloc. This approach is
      relatively safe and with few complications.

PMID- 17456357
TI  - [Diagnosis and treatment of spinal cord hemangioblastoma].
AB  - OBJECTIVE: To study the diagnosis and treatment of spinal cord hemangioblastoma.
      METHOD: The clinical data of 42 patients with spinal cord hemangioblastoma who
      were operated on between 1997 and 2005 were analyzed. RESULT: Spinal cord
      hemangioblastoma mostly showed space occupying lesions with clear boundary and Dd
      DTPA homogenous enhancement by MRI. All the 42 patients underwent complete
      excision. 27 patients showed improvement of their symptoms, the 6 patients failed
      to show any change, and neurological deficits were aggravated in the 5 patients.
      CONCLUSION: MRI and DSA are helpful in qualitative and localized diagnoses of the
      spinal cord hemangioblastoma. Surgical outcomes are favorable.

PMID- 17456358
TI  - [Endoscopic treatment of suprasellar arachnoid cysts].
AB  - OBJECTIVE: To analyze the clinical manifestation and neuroendoscopic techniques
      in treatment of suprasellar arachnoid cysts. METHODS: Between October 2000 and
      June 2006, 42 patients (22 male and 20 female with a mean age of 10.4 years) with
      suprasellar arachnoid cysts were treated by endoscopy. All patients presented
      with hydrocephalus in CT and MRI scanning before operation. Endoscopic
      ventriculocystostomy was performed in 39 patients and cystocisternostomy was also
      performed in the other 3 patients. The mean duration of follow-up was 20.8
      months. RESULTS: There was no surgery-related death and only two patients (4.8%)
      had postoperative complications. 25 cases (59.5%) recovered completely and 14
      cases (33.3%) improved clinically. Ventriculoperitoneal shunting was performed in
      3 patients because of recurrent hydrocephalus. Postoperative CT or/and MRI showed
      cyst volume decreased in all cases. Cine-MR imaging was performed in 21 patients
      that confirmed CSF could flow through all fenestration sites and aqueduct
      fluently. CONCLUSIONS: Endoscopic ventriculocystostomy
      (ventriculocystocisternostomy) is an effective and safe method in the treatment
      of suprasellar arachnoid cysts.

PMID- 17456359
TI  - [The neural substrates for voice familiarity in schizophrenic patients with
      auditory verbal hallucinations: an event-related functional magnetic resonance
      imaging study].
AB  - OBJECTIVE: To study the physiologic base of voice familiarity (VF) and the
      mechanism of auditory verbal hallucination (AVH) in the patients with
      schizophrenia (SCH). METHODS: Twenty-six schizophrenic patients, 13 with and 13
      without AVH, and 13 healthy control subjects were instructed to passively listen
      to familiar or unfamiliar voices and to give their judgment and underwent event
      related functional magnetic resonance imaging (efMRI) based on blood oxygenation
      level-dependent (BOLD) signal efficacy. The functional images were collected by
      using a 1.5-T MRI and were analyzed by using statistical parametric mapping 2
      (SPM2). RESULTS: The total score of positive symptoms of the SCH patients with
      AVH was (45.5 +/- 13.2), significantly higher than that of the SCH patients
      without AVH [(22.2 +/- 6.7), P < 0.05]. In comparison with unfamiliar voices,
      familiar voices elicited greater responses in the left superior temporal gyrus,
      right frontal lobe and limbic lobe among the SCH patients with AVH (P < 0.005,
      K(E) > 10). IN comparison with healthy control group, when the patients with AVH
      discriminated the familiar voices their left precuneus lobes were activated more
      significantly, and when they discriminated unfamiliar voices their right frontal
      lobes were activated more significantly (P < 0.005, K(E) > 10). In comparison
      with the SCH patients without AVH when the SCH patients with AVH discriminated
      the familiar voices their right frontal lobe were activated more significantly (P
      < 0.005, K(E) > 10), however, when they discriminated unfamiliar voices there was
      not significantly difference in the activation of the right frontal lobe between
      these groups. CONCLUSION: The efMRI results of the inter-group comparison support
      the inner speech disorder hypothesis that the activation of inner speech in the
      SCH patients with AVH inhibits the activation of external voice on the
      corresponding cerebral areas. In addition, hallucinating patients may have
      significant change of VF neurocognitive model.

PMID- 17456360
TI  - [Establishment of a method of contact heat evoked potential and its application
      in carpal tunnel syndrome].
AB  - OBJECTIVE: To establish a method to evoke cerebral potentials by stimulating
      nociceptive fibers, estimate the conduction velocities of nerve fibers mediating
      these responses, and assess the value of the potentials in carpal tunnel
      syndrome. METHODS: One hundred patients with carpal tunnel syndrome and 20 sex-,
      and aged-matched healthy persons underwent stimulation of contact heat delivered
      via a circular thermode to excite selectively nociceptors with a rapid rising
      time at 70 degrees C/s to elicit pain and contact heat evoked potential (CHEP).
      Thermal stimuli were sent at two intensity levels (49.5 degrees C and 54.5
      degrees C) to three body sites: thenar eminence, dorsum of hand, and proximal
      volar forearm The CHEPs were recorded from Cz and Pz. The relation between the
      stimulus intensity and pain rating was observed, and the main components of the
      evoked potential were recorded. The nerve conduction velocity was calculated from
      the latency difference of the CHEP and center to center distance of distal and
      proximal stimulus arrays. RESULTS: The pain intensity ratings were 3.2 +/- 0.3
      and 4.4 +/- 0.5 when the thenar eminence was stimulated at the temperature of
      49.5 degrees C and 54.5 degrees C respectively; and the ratings were 6.3 +/- 0.8
      and 7.2 +/- 0.5 on the dorsum of hand and proximal volar forearm at the
      temperature of 54.5 degrees C respectively. Three components, Cz/N550, Cz/P750,
      and Pz/P1000, were found in the evoked potentials. The latency of the CHEP was
      significantly correlated with the arm length, and not significantly correlated
      with sex, age, and side difference of the arm. The conduction velocities of the
      Adelta and C fibers of the carpal tunnel syndrome patients were 12.0 m/s +/- 5.6
      m/s and 0.6 m/s +/- 0.1 m/s respectively, both lowered, being 93.8% and 99.5% of
      those of the healthy persons (12.9 m/s +/- 7.5 m/s and 1.7 m/s +/- 0.4m/s
      respectively). CONCLUSION: Elicited reliably, CHEP is mediated by Adelta and C
      fibers. The conduction velocity of C fibers in the patients with carpal tunnel
      syndrome is decreased.

PMID- 17456361
TI  - [Nuclear and cytoplasmic expressions of survivin in glioma and their prognostic
      value].
AB  - OBJECTIVE: To investigate the nuclear and cytoplasmic expressions of survivin in
      human glioma, and their correlations to clinicopathological characteristics and
      prognosis. METHODS: A tissue microarray (TMA) based on 94 patients with glioma
      was constructed and then immunohistochemistry was used to examine the nuclear and
      cytoplasmic expressions of survivin in these glioma cohorts. Their correlations
      with clinicopathological characteristics and prognosis were analyzed. RESULTS:
      Among the 94 samples of glioma, nuclear survivin was detectable in 21 (22.3%)
      cases and cytoplasmic survivin in 82 cases (87.2%). The positive rate of nuclear
      expression of survivin was significantly lower in grade I - II gliomas than in
      the grade III - IV gliomas (7.3% vs 34.0%, P = 0.005). Statistically significant
      associations were observed between nuclear survivin and recurrence (P = 0.031).
      Cytoplasmic expression of survivin was not related to any clinicopathological
      characteristics. The 5-year overall survival rate and 3-year progression-free
      survival rate were significantly lower in the nuclear survivin-positive group
      than in nuclear survivin-negative group (0% vs 39.50%, P < 0.001; 0% vs 27.52%, P
      = 0.021). The 5-year overall survival rate and 3-year progression-free survival
      rate in the cytoplasmic positive-group and negative-group were 43.60% vs 13.85%
      (P = 0.134), and 23.88% vs 0% (P = 0.965) respectively. A multivariate analysis
      was conducted according to the Cox regression model. The significantly
      independent prognostic factors for overall survival were nuclear expression of
      survivin, grade and age. The relative risk of death in the patients whose tumors
      were survivin positive compared with those whose tumors were survivin negative
      was 3.847. CONCLUSION: Nuclear expression of survivin is correlated with glioma
      differentiation and recurrence. It is a negative prognostic factor for
      progression-free survival and overall survival in patients with glioma.

PMID- 17456362
TI  - [Automatic auditory information management in panic disorder patients: an event
      related potentials study].
AB  - OBJECTIVE: To investigate the characteristics of automatic auditory information
      management in sufferers of panic disorder (PD). METHOD: Mismatch negativity
      (MMN), as a component of event-related potentials, was recorded from 15 PD
      patients, 8 males and 7 females, aged 40 +/- 12, and 15 sex, and aged-matched
      controls. Repeated measures ANOVA was used on 4 representative electrodes: T3,
      T4, F3, and F4. RESULTS: Compared with the normal controls, the PD patients
      showed significant enlargement of MMN amplitude in 60 - 210 ms latency windows
      (60 - 110 ms: F(1, 28) = 11.413, P = 0.02; 110 - 160 ms: F(1, 28) = 6.639, P =
      0.016; 160 - 210 ms: F(1, 28) = 5.758, P = 0.023), and exhibited early (60 - 160
      ms) left encephalic region predominant effect. CONCLUSION: PD patients may deal
      excessive automatic processing of the auditory information changes which may
      assist in offering new objective evidence to understand the etiology of PD.

PMID- 17456363
TI  - [Application of the improved MTT assay in predicting the intrinsic drug
      resistance of liver cancer].
AB  - OBJECTIVE: To investigate the role of the improved MTT assay in prediction of
      intrinsic drug resistance of liver cancer. METHODS: The convenient MTT
      colorimetry was innovated to test the effects of 4'-epi-adriamycin (E-ADM),
      carboplatin (CBP), and 5-Fluorouracil(5-Fu), used alone or in combination, on 30
      specimens of primary liver cancer without chemotherapy. All of the 30 paraffin
      embedded tissues were assembled in a microarray. The used terminal concentrations
      of drugs were one twentieth those of the plasma peak concentrations calculated by
      using the liver cancer cells of the line SMMC-7721. The expression of P
      glycoprotein (P-gp), multidrug resistant protein (MRP)-3, lung resistance-related
      protein (LRP), glutathione S-transferase (GST)-pi, and 2 kinds of cyclin-related
      protein: p16(INK4a) and p21WAF1, were detected by immunohistochemistry. RESULTS:
      Sixteen of the 30 specimens (53.3%) were drug-resistant and 14 of the 30
      specimens (46.7%) were drug-sensitive. The sequence of drug -sensitivity was in
      the order of combination chemotherapy, E-ADM, 5-Fu, and CBP. The positive rate of
      P-gp in the drug-resistant group was 56.3%, significantly higher than that of the
      drug-sensitive group (14.3%, P < 0.05). CONCLUSION: An improved MTT assay has
      been developed that is more scientific and worth spreading clinically. Intrinsic
      drug resistance of liver cancer is popular. P-gp is a good predictive marker in
      intrinsic drug resistance of liver cancer.

PMID- 17456364
TI  - [The effect of two newly Chinese presenilin-1 mutations on the sensitivity to
      trophic factor withdrawal in human neuroblastoma cells].
AB  - OBJECTIVE: To study the effects of two novel presenilin-1 (PS1) mutations, V97L
      and A136G, discovered in 2 families of Alzheimer's disease (AD) in China, on
      human neuroblastoma cells and the protective role of insulin-like growth factor-1
      (IGF-1). METHODS: Two mutation type (MT) PS-1 genes with the mutational sites
      V97L and A136G were established. These 2 MT genes, wild type (WT) PS-1 gene, and
      mock were stably transfected into the human neuroblastoma cells of the line SH
      SY5Y. The 4 kinds of transfected cells were divided into 3 subgroups: (1) control
      subgroup, cultured in normal medium with serum, (2) serum deprivation subgroup,
      cultured in the medium without serum, and (3) serum deprivation + IGF-1 subgroup,
      cultured in serum deprivation medium plus IGF-1. Twenty-four hours later MTT
      colorimetry was used to calculate the cell survival rate. Hoechst33258 method and
      phosphatidylinositol/annexin V-FITC double staining flow cytometry were used to
      observe the cell apoptosis. The glucose uptake was measured. Western blotting was
      used to analyze the protein expression of glucose transporter protein (GLUT)-1 in
      the cell membrane. RESULTS: Different tests all showed that the cell survival
      rates of the V97L and A136G serum deprivation subgroups were both significantly
      lower than those of the corresponding WT and Mock subgroups (P < 0.01, P < 0.05),
      the cell survival rates of the all serum deprivation + IGF-1 subgroups were
      significantly higher than those of the corresponding serum deprivation subgroups
      (all P < 0.01); The glucose uptake rate was not significantly different among
      different subgroups, but IGF-1 addition made the glucose uptake increase by about
      25% (all P > 0.05). The GLUT1 expression in the cell membrane of the serum
      deprivation + IGF-I subgroups increased by 15% - 20% respectively, however,
      without significant differences. CONCLUSION: Enhanced sensitivity to trophic
      withdrawal in the cells with the two Chinese PS1 mutations most likely
      contributes to the neuron loss in AD. The sensitivity to apoptosis is not caused
      by impaired glucose metabolism, but IGF-1 still can protect cells from serum
      deprivation that compensates the negative effect through enhancing glucose
      transport and mitochondria activities.

PMID- 17456365
TI  - [Correlation between hippocampal mossy fiber sprouting and synaptic
      reorganization and mechanisms of temporal lobe epilepsy].
AB  - OBJECTIVE: To explore the effects of the ultrastructural features of sprouted
      mossy fiber synapses in the mechanism of temporal lobe epilepsy. To explore the
      correlation between axon guidance molecule-netrin-1 gene expression and mossy
      fiber synaptic reorganization. METHODS: Sixty-one SD rats underwent
      intraperitoneal injection of lithium chloride and pilocarpine to establish models
      of status epilepticus characterized with temporal lobe epilepsy. Nineteen rats
      were used as controls. One, 2, and 4 weeks after the injection, a certain numbers
      of rat were killed with their brains taken out. The sprouted mossy fiber synaptic
      terminals were labeled by Timm histochemistry and the ultrastructure of new
      synapses were observed by electron microscopy. By in situ hybridization, the mRNA
      expression of netrin-1 gene was observed. RESULTS: The sprouted mossy fiber
      synapses in epileptic rats most commonly formed asymmetric synapses with
      dendritic spines and occasionally with granule cell somata. Seven days after the
      injection, up-regulation of netrin-1 mRNA expression was seen in the dentate
      granule cell layers of hippocampus and continued to 4 weeks after the injection.
      The time course of the increase of netrin-1 mRNA in the dentate granule cell
      layers was correlated with the time course of mossy fiber sprouting and synaptic
      reorganization in hippocampus. CONCLUSION: The ultrastructural features of
      sprouted mossy fiber synapses support the viewpoint that the reorganization of
      synapses prominently involves the formation of recurrent excitatory circuits. The
      axon guidance molecule- netrin-1 plays an important role in the process of mossy
      fiber axonal outgrowth and synaptogenesis in the hippocampal dentate gyrus.

PMID- 17456366
TI  - [The effects of somatostatin on serum interleukin-6 and tumor necrosis factor
      alpha in lipopolysaccharide-induced septic shock: experiment with rats].
AB  - OBJECTIVE: To explore the effect of somatostatin on serum interleukin (IL)-6 and
      tumor necrosis factor (TNF)-alpha in lipopolysaccharide (LPS)-induced septic
      shock. METHODS: 24 male Wistar rats were randomly divided into 2 groups:
      intervention group (injected with LPS of Escherichia coli via femoral vein to
      induce septic shock) and control group (injected with LPS of Escherichia coli and
      then injected with somatostatin). The mean arterial pressure (MAP), heart rate,
      respiration rater, and mortality rate were observed before the injection of LPS,
      and 30, 90, and 360 min after the injection, and the serum IL-6 and TNF-alpha
      level were detected before the injection of LPS, 30, 90, and 360 min after the
      injection, or after the death. RESULTS: The IL-6 levels 30 min, 90 min, and 360
      min after the injection of the somatostatin intervention group were 233 +/- 47,
      212 +/- 33, and 217 +/- 26 mg/L respectively, all significantly lower then those
      of the control group (308 +/- 56, 260 +/- 32, and 230 +/- 92 mg/L, all P < 0.05).
      The TNF-alpha level 30 min, 90 min, and 360 min after the injection of the
      somatostatin intervention group were 450 +/- 82, 417 +/- 92, and 440 +/- 49 mg/L,
      all significantly lower than those of the control group (607 +/- 149, 517 +/- 74,
      and 474 +/- 219 mg/L, all P < 0.05). In addition, compared with the control
      group, the MAP of the somatostatin intervention group increased after 90 min. Two
      rats in the control group died 30 to 90 min later and 4 rats died 90 to 360 min
      later, however, 360 min later all rats in the somatostatin intervention group
      were alive (P = 0.0054). CONCLUSION: Somatostatin can inhibit the level of serum
      IL-6 and TNF-alpha in septic shock induced by LPS and improve the survival rate.

PMID- 17456367
TI  - [Upstream signaling pathway of neutrophil elastase-induced mucous
      hypersecretion].
AB  - OBJECTIVE: To investigate the upstream signal transduction pathway of neutrophil
      elastase (NE)-induced mucous hypersecretion via epidermal growth factor receptor
      (EGFR). METHODS: The airway epithelial cells of the line BEAS-2B were cultured
      and divided into 6 groups: control group, cultured in serum-free DMEM/Ham's F12
      mixture; NE group, incubated with NE alone, transforming growth factor (TGF)
      alpha protease inhibitor (TAPI)-1 + NE group, incubated with NE and TAP I-1; 1, 3
      dimethyl-2-thiourea (DMTU) + NE group, preincubated with DMTU, a reactive oxygen
      species (ROS) scavenger, and then incubated with NE; TGF-alpha group, incubated
      with TGF-alpha; and DMTU + TGF-alpha group, incubated with DMTU and TGF-alpha.
      The mucin (MUC) 5AC mRNA level was analyzed by RT-PCR, MUC5AC protein and soluble
      TGF-alpha were detected by enzyme-linked immunosorbent assay, and the
      phosphorylated EGFR (p-EGFR) protein production was assayed by Western blotting.
      RESULTS: The MUC5AC mRNA expression and protein expression of the NE group were
      0.81 +/- 0.13 and 0.78 +/- 0.06 respectively, both significantly higher than
      those of the control group (0.32 +/- 0.07 and 0.24 +/- 0.08 both P < 0.01. The
      protein expression of soluble TGF-alpha and the protein expression of p-EGFR
      protein of the NE group were 0.83 +/- 0.14 and 0.88 +/- 0.07 respectively, both
      significantly higher than those of the control group (0.25 +/- 0.13 and 0.28 +/-
      0.11 respectively, both P < 0.01). The expression rates of MUC5AC mRNA, MUC5AC
      protein, soluble TGF-alpha, and p-EGFR of the TAPI-1 group were 0.37 +/- 0.04,
      0.30 +/- 0.11, 0.32 +/- 0.07, and 0.43 +/- 0.09 respectively, all significantly
      lower than those of the NE group (all P < 0.01). The level of MUC5AC mRNA, MUC5AC
      mucin protein, and soluble TGF-alpha of the DMTU + NE group were 0.36 +/- 0.03,
      0.39 +/- 0.12, and 0.43 +/- 0.05 respectively, all significantly lower than those
      of the NE group (all P < 0.01), however, the MUC5AC mRNA expression and MUC5AC
      protein expression of the DMTU + TGF-alpha group were 0.58 +/- 0.13 and 0.55 +/-
      0.11 respectively, both not significantly different from those of the TGF-alpha
      group (0.56 +/- 0.08 and 0.57 +/- 0.13 respectively, both P > 0.05). CONCLUSION:
      NE induces MUC5AC expression via ROS/TACE/pro-TGF-alpha/EGFR in the airway
      epithelial cells.

PMID- 17456372
TI  - [Advance in cardiomyopathy research].

PMID- 17456373
TI  - [Focusing on high density lipoprotein: from quantity to quality].

PMID- 17456374
TI  - [Activation of transforming growth factor-beta1/Smads signal pathway in diabetic
      cardiomyopathy and effects of valsartan thereon: experiment with rats].
AB  - OBJECTIVE: To study the activation of transforming growth factor (TGF)
      beta(1)/Smads signal pathway in diabetic cardiomyopathy (DCM) and effects of
      valsartan thereon. METHODS: 40 male Wistar rats were randomly divided into 3
      groups: DCM group (n = 16, fed with high-calorie fat diet for 4 weeks, injected
      intraperitoneally with streptozocin so as to establish DCM model, and then
      perfused into the stomach with normal saline once daily since the injection of
      STZ for 16 weeks), valsartan group (n = 16, perfused into the stomach with
      valsartan at the dose of 30 mg/kg once a day for 16 weeks after the establishment
      of DCM model), and control group (n = 8, fed with normal diet and perfused into
      the stomach with normal saline once daily for 16 weeks). At the end of the
      experiment, the contents of fast blood-glucose (FBG), fast insulin (FIN), serum
      cholesterol, and triglyceride were detected, and insulin sensitivity index (ISI)
      was calculated. Cardiac catheterization was performed to measure the hemodynamics
      indexes: left ventricular systolic pressure (LVSP), left ventricular end
      diastolic pressure (LVEDP), and maximal rise/fall velocity of ventricular
      pressure (+/- dp/dt(max)), and the left ventricular diastolic function (T) was
      calculated. Pieces of myocardium tissue were taken out to undergo ultrastructural
      histopathological examination by transmission electron microscopy. The content of
      collagen was quantified by Masson three-color staining. Real-time RT-PCR and
      Western-blotting were used to detect the mRNA expression and protein expression
      of TGFbeta(1), TGFbetaRII, Smad2, Smad3, and Smad7. RESULTS: By the end of
      experiment the levels of FBG, triglyceride, and cholesterol increased and the ISI
      decreased significantly in the DCM and valsartan groups (all P < 0.01). Compared
      with the valsartan and control groups the levels of LVEDP and T significantly
      increased, and the levels of LVSP and +/- dp/dt(max), significantly decreased
      (all P < 0.01); and the LVEDP of the valsartan group was significantly higher
      than that of the control group and the +/- dp/dt(max) of the valsartan group was
      significantly lower than that of the control group (P < 0.01). The volume of
      collagen in the myocardial tissue of the DCM group was 17% +/- 3%, significantly
      higher than that of the control group (11% +/- 3%, P < 0.01). The content of
      collagen in the myocardial tissue of the valsartan group was lower significantly
      than that of the DCM group. The levels of mRNA expression of TGFbeta(1),
      TGFbetaRII, Smad2, and Smad3 were 0.0126 +/- 0.0057, 0.0877 +/- 0.0272, 0.0884 +/
      0.0146, and 0.012 +/- 0.0048 respectively, all significantly higher than those
      of the control group (0.0054 +/- 0.0009, 0.0523 +/- 0.0218, 0.0413 +/- 0.0186,
      and 0.0064 +/- 0.0021 respectively, all P < 0.05 - 0.01). The ratios Smad2/Smad7
      and Smad3/Smad7 of the DCM group were significantly higher than those of the
      control group (both P < 0.05). The protein levels of TGFbeta(1), P-Smad2, and P
      Smad3 were 143 +/- 17, 212 +/- 43, and 151 +/- 32 respectively, all significantly
      higher than those of the control group (103 +/- 18, 107 +/- 21, and 89 +/- 17
      respectively, P < 0.01). The P-Smad2/Smad7 and P-Smad3/Smad7 of the DCM group
      were significantly higher than those of the control group (both P < 0.05), The
      Smad2/Smad7 (or P-Smad2/Smads7) and Smad3/Smad7 (or P-Smad3/Smads7) of the
      valsartan group was significantly lower than those of the DCM group (both P <
      0.05). CONCLUSION: Activation of TGFbeta(1)/Smads signal pathway and imbalance
      between Smad2, 3 and Sma7 may be one of the mechanisms of myocardial interstitial
      fibrosis in DCM. Valsartan can prevent myocardium from damage by blocking the
      signal pathway.

PMID- 17456375
TI  - [Family hypertrophic cardiomyopathy caused by a 14035c > t mutation in cardiac
      troponin T gene].
AB  - OBJECTIVE: To study the disease-causing gene mutation in Chinese patients with
      familial hypertrophic cardiomyopathy (FHC) and to analyze the correlation between
      the genotype and the phenotype. METHODS: Peripheral blood samples were collected
      from 40 members from a family affected with FHC, and 120 healthy volunteers. PCR
      was performed to analyze the exons and flanking introns of the cardiac troponin T
      gene (TNNT2), beta-myosin heavy chain gene (MYH7), and myosin-binding protein C
      gene (MYBPC3) and the products were sequenced. The clinical data including
      symptom, physical examination, echocardiography and electrocardiography were
      collected. RESULTS: A 14035c > t mutation, which causes a missense mutation
      (R130C) in exon 10 of TNNT2 gene were identified in 4 family members, including
      the proband, female, aged 53, with the onset at the age of 30. The 4 persons with
      the 14035c > t mutation, all FHC patients, presented left ventricular dysfunction
      with a penetrance of 100%. Two of the patients died of sudden cardiac death
      during follow-up. No mutation was identified in the MYH7 and MYBPC3 genes.
      CONCLUSION: The 14035c > t mutation of TNNT2 gene is the causal mutation of FHC
      which is associated with malignant phenotype with a penetrance of 100%. It is a
      reasonable procedure in HCM patients with malignant phenotype to screen mutation
      in the TNNT2 gene.

PMID- 17456377
TI  - [Expression of phosphatidylinositol 3-kinase and effects of wortmannin on the
      expression of tumor necrosis factor-alpha in ulcerative colitis].
AB  - OBJECTIVE: To elucidate the role of phosphatidylinositol 3-kinase (PI3K)/Akt in
      the pathogenesis of ulcerative colitis (UC) and provide experimental evidence
      that PI3K inhibitor wortmannin can be used as a possible novel approach for
      treatment of UC. METHODS: Samples of intestinal mucosa were collected from 30 UC
      patients, 22 males and 8 females, aged 35 +/- 11, during enteroscopy. Samples of
      normal intestinal mucosa 10 cm beyond the cancerous tissues were collected from
      15 patients with intestinal cancer, 9 males and 6 females, aged 40 +/- 9, as
      normal controls. The samples underwent pathological examination and
      immunohistochemistry. Another tissues of intestinal mucosa were cultured and
      divided into 3 groups: UC + wortmannin group, (n = 10, wortmannin, an inhibitor
      of PI3K/Akt pathway, of the concentration of 0.002 nmol/microl was added), UC
      control group (n = 10, without addition of wortmannin), and peri-cancer normal
      intestinal tissue group (n = 10). 4.5 hours after the culture,
      immunohistochemistry was used to detect the expression of phosphorylated Akt (p
      Akt) in the intestinal mucosa and ELISA was used to detect the content of tumor
      necrosis factor (TNF-alpha) in intestinal mucosa. RESULTS: (1) The A value of p
      Akt in the intestinal mucosa of the UC control group was 73.6 +/- 5.2,
      significantly higher than that of the normal control group (18.0 +/- 2.6, P <
      0.05), the positive area of the UC control group was 720 +/- 58, significantly
      larger than that of the normal control group (133 +/- 29, P < 0.05). (2) The
      level of TNF-alpha in intestinal mucosa of the UC + wortmannin group was 135 +/-
      11, significantly lower than that of the UC control group (296 +/- 39, P < 0.05),
      however, still significantly higher than that of the normal control group (26 +/-
      5, P < 0.05). (3) The A value of p-Akt in the intestinal mucosa biopsy specimens
      of the UC + wortmannin group was 35.3 +/- 5.6, significantly lower than that of
      the UC control group (72.3 +/- 6.2, P < 0.05), however, still significantly
      higher than that of the normal control group (18.0 +/- 2.2, P < 0.05); and the
      positive area of the UC + wortmannin group was 351 +/- 50, significantly lower
      than that of the UC control group (716 +/- 94, P < 0.05), however, still
      significantly higher than that of the normal control group (129 +/- 30, P <
      0.05). CONCLUSIONS: (1) PI3K/Akt signal transduction pathway is a critical factor
      in regulating the expression of pro-inflammatory cytokine, and plays a role in
      the pathogenesis of UC. (2) Decreasing the levels of relevant cytokines in UC by
      inhibiting PI3K/Akt signal transduction pathway, wortmannin may be a novel
      approach for the treatment of UC.

PMID- 17456378
TI  - [Psychological status of congenital microtia patients and relative influential
      factors: analysis of 410 cases].
AB  - OBJECTIVE: To investigate the psychologic status of congenital microtia patients
      and related influential factors. METHODS: In a cross-sectional survey for
      congenital microtia, 410 patients, 314 males and 96 females, aged 12 +/- 6 (5 -
      37), underwent psychological survey with the symptom checklist-90 (SCL-90) or
      Achenbach child behavior checklist (CBCL), centering on the 3 main psychological
      problems: depression, interpersonal sensitivity or social difficulties, and
      hostility or aggression. A questionnaire was designed to investigate the
      influencing factors, such as the patients' own factors, and psychological factors
      of the patients' families Chi square test and logistic regression analysis were
      performed to find the factors contributing to those psychological problems.
      RESULTS: Psychological status of congenital microtia patients were depression
      existed in 83 patients (20.2%), interpersonal sensitivity or social difficulties
      existed in 150 patients (36.6%), and hostility or aggression existed in 108
      patients (26.3%). The factors, such as age (OR = 1.75), microtia grade (OR =
      2.77), mother's education (OR = 2.49), having been subjected to ridicule (OR =
      2.58), pressure of family affection (OR = 1.96), family attitude to patient (OR =
      2.45), and deficiency of family harmony (OR = 2.57) were risk factors
      contributing to depression of patients. The factors, such as age (OR = 1.62),
      having been subjected to ridicule (OR = 3.34), and pressure of family affection
      (OR = 1.89) were risk factors contributing to interpersonal sensitivity or social
      difficulties of the patient. The factors, such as having been subjected to
      ridicule (OR = 2.47), and pressure of family affection (OR = 1.80) were risk
      factors contributing to hostility or aggression of the patient. CONCLUSION:
      Having been subjected to ridicule, deficiency of family harmony, and pressure of
      family affection are mainly risk factors of psychological problems of congenital
      microtia patients. Early education and early operation for the patients are
      necessary.

PMID- 17456379
TI  - [Effectiveness and safety of intragastric balloon for treatment of morbid
      obesity].
AB  - OBJECTIVE: To evaluate the effectiveness and safety of intragastric balloon (IGB)
      for the treatment of obese Chinese. METHODS: IGB was placed into the stomachs of
      48 Chinese patients in Hong Kong, 13 males and 35 females; aged 39 +/- 9 (18 -
      65), with the mean baseline body weight (BW) of 106 +/- 26 kg and mean body mass
      index (BMI) of (40 +/- 9) kg/m(2), 34 (70.8%) with coexistent obesity-related
      morbidities, who failed to respond to other weight reducing treatment, via
      routine gastroscopy under intravenous conscious sedation. Restricted balanced
      diet with 1200 kcal/day and exercise of 150 minutes/week were prescribed after
      the balloon placement. The IGB was removed endoscopically after at most 180 days.
      Follow-up was conducted once a week during the first month and then once a month.
      RESULTS: The median hospital stay and treatment duration were 1 (IQR 1:2.25) day
      and 174 (IQR 166:181) days respectively. The BW, BMI, and waist circumference
      were significantly decreased after the IGB placement (all P < 0.01) with the mean
      BW loss of (13 +/- 7) kg, mean BMI loss of (5 +/- 3) kg/m(2), mean excessive body
      weight loss of (45 +/- 36)%, and mean waist circumference loss of (12 +/- 8) cm.
      66.7% of the patients were satisfied with the treatment. No serious complication
      related to IGB was noted. CONCLUSION: IGB is a safe and effective device that
      achieves moderate weight loss in obese Chinese.

PMID- 17456380
TI  - [Changes of intercellular spaces of esophageal epithelium in patients with
      gastroesophageal reflux disease before and after esomeprazole treatment].
AB  - OBJECTIVE: To observe the changes of dilated intercellular space (DIS) of
      esophageal epithelium in different subtypes of gastroesophageal reflux disease
      (GERD) before and after esomeprazole treatment. METHODS: Nineteen patients with
      GERD, 6 with erosive esophagitis (EE), 7 with NERD with abnormal acid exposure
      (NERD pH+), and 6 with NERD with normal acid exposure (NERD pH-), were treated
      with esomeprazole 40 mg daily for two months. During endoscopy before and after
      treatment, six biopsy specimens were taken from the apparently normal mucosa 3 -
      5 cm above the dentate line in the esophagus to undergo HE staining and
      histological examination and transmission electron microscopy (TEM). Fifteen
      normal subjects were used as controls. RESULTS: Two months after the treatment 5
      cases (83.33%) in the EE group, 6 cases (85.57%) in the NERD pH+ group, and 5
      cases (83.33%) in the NERD pH- group showed a complete recovery of DIS and
      complete disappearance of the symptom of heartburn. Two of the left three
      patients who showed incomplete recovery of DIS still had heartburn. CONCLUSION: A
      complete recovery of DIS 2 months after treatment of esomeprazole is always
      accompanied by resolution of heartburn symptom. No significant difference in
      complete recovery of DIS can be found among different GERD subgroups.

PMID- 17456381
TI  - [Association between retinoic acid receptor alpha gene polymorphisms and
      nonsyndromic cleft lip with or without cleft palate susceptibility].
AB  - OBJECTIVE: To investigate the relationship between D17S579 microsatellite marker
      allelic polymorphisms in retinoic acid receptor-alpha (RARA) gene and the genetic
      susceptibility to nonsyndromic cleft lip with or without cleft palate (NSCL/P) in
      Hunan Hans. METHODS: PCR and denaturing polyacrylamide gel electrophoresis (PAGE)
      were used to detect the polymorphism of RARA gene marked by D17S579 among 140
      patients with NSCL/P, 82 males and 58 females, aged 3 months-14 years, and 132
      healthy persons, 68 males and 64 females, aged 6 months-14 years, who underwent
      physical examination. RESULTS: The A6 allele frequency of the NSCL/P patients was
      8.93%, significantly higher than that of the healthy persons (4.17%, P = 0.026).
      The A9 allele frequency the NSCL/P patients was 13.21%, significantly higher than
      that of the healthy persons (5.68%, P = 0.003). There were not significant
      differences in the frequencies of different alleles between the patients with
      family history and the patients without family history (chi2 = 2.710, P = 0.978).
      CONCLUSION: The A6 and A9 alleles in D17S579 microsatellite marker of RARA gene
      may be correlated with the development of NSCL/P in Hunan Hans. There is no
      association between the family history and RARA polymorphism in the NSCL/P
      patients.

PMID- 17456382
TI  - [Enhanced translational efficacy of internal ribosomal entry site-mediated mRNA
      in dendritic cells contributes to efficient induction of antitumor immunity].
AB  - OBJECTIVE: To develop a more economic and applicable substitute for modification
      of dendritic cells (DCs) by capped mRNA in induction of anti-tumor immunity.
      METHODS: Four DNA plasmids as templates of mRNA in vitro transcription were
      constructed: pmRNA luciferase (Luc), pmRNA internal ribosomal entry site (IRES)
      Luc, pmRNA ovalbumin (OVA), and pmRNA IRES-OVA. The translational efficiency of
      uncapped-Luc, capped-Luc, or IRES-Luc mRNA in murine DCs was detected via a Luc
      reporter system. Nine C57BL/6 mice were divided into 3 equal groups to be
      injected intraperitoneally with DCs transfected with IRES-OVA or capped-OVA mRNA
      and untreated DCs respectively, 1 weeks later the mice were injected with
      splenocytes wrapped with the target peptide or control peptide labeled by CFSE,
      and 4 hours later the mice were killed and suspension of splenocytes was made to
      test the activity of cytotoxic lymphocytes (CTLs). Another 30 mice were divided
      into 3 equal groups to undergo immunization by DCs as mentioned above, 1 week
      later mice melanoma cells of the line MO5 stably expressing OVA were injected the
      caudal vein, and 3 weeks later the mice were killed and their lungs were taken
      out to observe the metastasis of tumor, using OVA as a target antigen. RESULTS:
      Insertion of IRES into upstream of gene of interest in mRNA transcriptional
      templates didn't affect the yield of mRNA in vitro transcription. The level of
      Luc activity expressed by IRES-Luc mRNA in the DCs was 20 times higher than that
      by expressed by Uncapped Luc mRNA, and one time higher than that by Capped-Luc
      mRNA 8 h after transfection of DC. Expression of Luc could be detected up to 96 h
      after the transfection with IRES-Luc and Capped-Luc mRNA. Four hours after the
      injection of peptides the CTL activity of the mice immunized with DCs pulsed with
      Capped-OVA mRNA was (28 +/- 3)%, not significantly different from that of the
      mice immunized with DCs pulsed with IRES-OVA mRNA [(32 +/- 4)%, P > 0.05]. Mata
      static melanoma nodules could be seen in all control mice, only one mouse of the
      Capped-OVA mRNA group, and none of the mice of the IRES-OVA mRNA group.
      CONCLUSION: IRES-containing tumor-associated antigen (TAA) mRNA as a more
      economic and applicable substitute fully replaces Capped-TAA mRNA for mRNA-based
      DC vaccines and DCs pulsed with IRES-containing TAA mRNA induces the same
      effective antigen-specific cellular response as the DCs pulsed with Capped-TAA
      mRNA.

PMID- 17456383
TI  - [Effects of inhibiting nucleosomal binding protein 1 on proliferation of human
      prostate cancer cells].
AB  - OBJECTIVE: To explore the role of nucleosomal binding protein 1 (NSBP1) in the
      proliferation of human hormone-dependent prostate cancer cells by inhibiting its
      mRNA expression. METHODS: Four well-designed short-hairpin RNA (shRNA) targeting
      NSBP1, including a negative control shRNA, were synthesized and inserted into the
      pSilencer 2.1-U6 neo plasmid. The pSilencer-81 plasmid was identified as the most
      efficient. The 4 recombinant plasmids, pSilencer-58, 81, 126, and Neg, were then
      transfected to human hormone-dependent prostate cancer cells of the line LNCaP,
      i.e., LNCap/81, LNCap/58, LNCap/126, and LNCap/Neg cells. RT-PCR and Western
      blotting were used to detect the inhibitory efficiency of different plasmids. MTT
      method was used to detect cell viability and flow cytometry was used to observe
      cell cycle distribution. RESULTS: Western blotting showed that the protein
      expression of NSBP1 in the LNCap/81 cells was lower by 85% compared to that in
      the LNCap/Neg cells. Compared with the control cells, the A values of the
      LNCap/81 cells 60, 84, 108, and 132 hours after transfection were all
      significantly lower than those of the LNCap/Neg cells (t = 4.501, 4.282, 5.229,
      and 4.759, all P < 0.05), showing that the cell viability was reduced. The
      proportions of cells in the G(2)M and S phases 60, 84, and 108 hours after
      transfection of the LNCap/81 cells were all significantly lower than those of the
      LNCap/Neg cells (t = 3.705, 3.887, and 8.220, all P < 0.05). CONCLUSION: The
      suppressed expression of NSBP1 in prostate cancer cells mediated by shRNA
      inhibits cell proliferation significantly, which indicates that NSBP1 may play an
      important role in the proliferation of prostate cancer cells.

PMID- 17456384
TI  - [The effects of lipiodol-hydroxyapatite nanoparticle on apoptosis, proliferation,
      and angiogenesis in hepatic tumor: experiment with rabbits].
AB  - OBJECTIVE: To investigate the effects of lipiodol-hydroxyapatite nanoparticle
      (lipi-nHAP) on the growth, necrosis, apoptosis, proliferation, and angiogenesis
      of hepatic tumor. METHODS: Ultrasound-emulsification was used to make lipi-nHAP
      Eighty New Zealand white rabbits underwent implantation of carcinoma cells of the
      line VX2 into the left lobe of liver. Two weeks later the rabbits underwent
      catheterization into the gastroduodenal artery so that, and then the rabbits were
      randomly divided into four equal groups to receive infusion via the hepatic
      artery of different drugs: physiological saline (Group A), lipiodol (Group B),
      adriamycin + lipiodol (Group C), and lipi-nHAP (Group D). Seven and 14 days after
      the treatment the size of tumor was observed by spiral CT scan, and the volume
      and growth rate of tumor were calculated. Two weeks after the treatment 8 rabbits
      from each group were killed and their liver tumors were taken out and the
      survival rates of remaining rabbits were observed. The necrosis rate of the liver
      tumor was assessed by measuring the area of the tumor and the necrosis. The
      apoptotic rate was examined by TUNEL method. Mcrovessel density (MVD) was
      examined by immunohistochemistry anti-CD31 antibody. Anti-proliferating cell
      nuclear antigen (PCNA) monoclonal antibody was used to detect the expression of
      PCNA so as to calculate the proliferation index of the cells. RESULTS: The tumor
      volume and growth rate of Group D 7 and 14 days after treatment were both
      significantly lower than those of other groups (all P < 0.05) and the necrosis
      rate and apoptotic index of Group D were both significantly higher than those of
      other groups (all P < 0.05). The values of MVD were higher in Groups C and D
      compared with those of Group A. Compared with those in other groups, the values
      of MVD and expression level of PCNA were significantly lower in group D (all P <
      0.05). The survival time of Group D was longer than those of other groups (all P
      < 0.05). CONCLUSION: lipi-nHAP can suppress the growth of tumor, increase the
      tumor's necrosis rate and apoptotic index, inhibit the development of
      neovascularization, decrease the expression level of PCNA of residual tumor, and
      prolong the surviving time of the animals with hepatic tumor. It may become an
      effective embolization material to treat liver cancer.

PMID- 17456385
TI  - [Multipotent adult progenitor cells from human bone marrow differentiate into
      hepatocyte-like cells induced by co-culture with human hepatocyte line].
AB  - OBJECTIVE: To investigate the possibility of multipotent adult progenitor cells
      from human bone marrow ZHJ-MAPC to differentiate into hepatocytes by co-culture
      with human hepatocyte line L02 in vitro. METHODS: (1) Multipotent adult
      progenitor cells from human bone marrow, screened in Zhujiang hospital, named ZHJ
      MAPC, were divided into 2 parts. Some ZHJ-MAPCs undergo co-culture with human
      hepatocytes of the line L-02 in the manner without cell to cell contact. On the
      days 1, 3, 5, and 7 immunocytochemistry was used to detect the expression of
      albumin (ALP), alpha-fetoprotein (AFP), cytokeratin (CK)-18, and CK-19,
      characteristic of hepatocyte. Some ZHJ-MAPC were labeled with Certified
      Functional Safety Expert (CFSE), a fluorescent reagent, and were mixed with L02
      cells so as to undergo co-culture in the manner with cell to cell contact. Then
      the mixed cells were seeded on specialized dish for detection by Laser Scanning
      Confocal Microscope (LSCM). 5 days later, the cells were double stained with SABC
      Cy3. The expression of ALP, AFP, and CK-18 in the ZHJ-MAPC were observed under
      LSCM. Separately cultured L02 hepatocytes served as positive control s and
      separately cultured ZHJ-MAPC served as negative controls. RESULTS: (1) Results of
      co-culture without cell to cell contact. On the first day, the ZHJ-MAPC expressed
      high level of AFP and then the AFP expression tapered daily. The expression of
      ALP was very weak on day 1 and then increased and peaked on day 5. The expression
      of CK-18 began to appear on day 5 and peaked on day 7. The expression of CK-19
      was always negative. (2) Results of co-culture with cell to cell contact. On day
      5 there were three colors of fluorescence under LSCM. Yellow cells represented
      the ZHJ-MAPC differentiating into hepatocytes; the green cells were
      undifferentiating ZHJ-MAPC; and the red cells were L02 hepatocytes. The result
      showed that ALP and CK-18 were expressed in many ZHJ-MAPC; AFP appeared only in a
      few cells. CONCLUSION: ZHJ-MAPC can be induced to differentiate into mature
      hepatocyte-like cells by co-culture, either with or without cell to cell contact.

PMID- 17456386
TI  - [Antisense RNA of survivin gene enhances the taxol-induced apoptosis and
      sensitivity to chemotherapy drugs in bladder cancer cells: an in vitro
      experiment].
AB  - OBJECTIVE: To evaluate the effects of antisense oligodeoxynucleotide (ASODN) of
      survivin gene on taxol-induced apoptosis in bladder cancer cells. METHODS: A
      survivin ASODN eukaryotic vector pcDNA3-SVVas was transfected into human bladder
      cancer cells of the line BIU87 mediated by liposomal reagent (BIU87 SVVas cells).
      The mRNA expression of survivin was measured by RT-PCR. Blank plasmid pcDNA3 was
      transfected as control (BIU87 neo cells). The cell growth curve was drawn using
      trypan blue dye exclusion assay. MTT assay was used to investigate the
      sensibility of transfected cells to taxol. The BIU87 SVVas cells, BIU87 neo
      cells, and BIU87 cells were cultured in the culture fluid with taxol and then DNA
      gel electrophoresis, Hoechst nuclear staining and fluorescent microscopy, and
      annexin-propidium iodide (PI) staining were used to examine the cell apoptosis.
      RESULTS: Compared to BIU87 and BIU87 neo cells, the mRNA expression of survivin
      in the BIU87-SVVas cells was obviously reduced. The growth of the BIU87-SVVas
      cells was significantly reduced in comparison with the BIU87 (P < 0.05). The
      sensibility of BIU87 SVVas cells to taxol increased significantly shown by cell
      proliferation and MTT assays. Agarose gel electrophoresis of genomic DNA showed
      typical DNA ladder only in the BIU87 SVVas cells, but not in other cells. Hoechst
      nuclear staining and fluorescent microscopy showed that the nuclei of the BIU87
      SVVas cells become condense. Annexin-PI test showed that the cell apoptosis rate
      of the BIU87-SVVas cells treated with taxol was significantly higher than those
      of the other groups. CONCLUSION: survivin antisense RNA enhances the taxol
      induced apoptosis in the bladder cancer cells. This may lay an experimental
      foundation for further research of biotherapy in bladder cancer.

PMID- 17456387
TI  - [Effect of tetrandrine on endothelin expression in the lungs and clinical
      significance thereof: experiment with rat models with nitrofen-induced congenital
      diaphragmatic hernia].
AB  - OBJECTIVE: To investigate the effects of tetrandrine on endothelin expression in
      the lungs and its clinical significance. METHODS: 25 pregnant female SD rats were
      randomly divided into 5 equal groups: Groups A to D were fed with nitrofen to
      cause congenital diaphragmatic hernia (CDH) in the fetuses. Group A was injected
      with normal saline, Group B with dexamethasone (DXM), Group C with tetrandrine,
      and Group D with DXM + tetrandrine. Group E was control Group. On day 21.5 of
      pregnancy the fetuses were delivered by cesarean section and killed. Microscopy
      was used to observe the CDH formation, and the relative wall thickness (RWA) and
      relative wall area (RWA) of pulmonary arterioles. The lung/body weight ratio, and
      relative integrated optical density (IOD) of pulmonary arteriole and bronchiole
      were observed. The expression of endothelin in the lung tissues was detected by
      immunohistochemistry. RESULTS: 9 rats of Group A-D produced 57 fetuses with CDH
      with a CDH arte of 45.2%. The lung/body weight ratios, and RWA values of Group A
      D were all significantly lower than that of Group E (all P < 0.05). The RWT of
      pulmonary arteriole was significantly lower in Groups B and C compared with Group
      E (both P < 0.05). The RWT and RWA of Group A were significantly lower than those
      of Group B-D (all P < 0.05). The values of relative IOD of pulmonary tissues and
      of pulmonary arteriole of Group A-D were all significantly lower than those of
      Group E (all P < 0.05). A positive correlation existed between the relative IOD
      of endothelin in pulmonary arteriole and in bronchiole (P < 0.01), and among the
      RWT and RWA of pulmonary arteriole, and relative IOD (all P < 0.01). CONCLUSION:
      Tetrandrine improves the pulmonary hypoplasia and degrades the pulmonary
      hypertension.

PMID- 17456392
TI  - [Expression of N-methyl-D-aspartate receptor 1 in acute intoxicated
      encephalopathy induced by 1,2-dichloroethane].
AB  - OBJECTIVE: To study the role of N-methyl-D-aspartate receptor 1 in acute
      intoxicated encephalopathy induced by 1,2- dichloroethane(1,2-DCE). METHODS:
      Forty-two Sprague-Dawley rats, which had been randomly divided into 1 control, 3
      exposure and 3 after-exposure observation groups were exposed to 1,2-DCE for 12
      hr by continual static inhalation except control group. Dosage of exposure groups
      was 5.0, 10.0, 20.0 g/m(3) on sequence. That of after-exposure observation groups
      was 10.0 g/m(3). Rats of after-exposure observation groups were observed
      continually for 2,4,6 hr after exposure. The expression of N-methyl-D-aspartate
      receptor-1 (NMDAR1) was detected by immunohistochemical method. RESULTS: NMDAR1
      stained neurons were mainly distributed at cerebral cortex and hippocampus.
      Compared with that of control group, the percentages of positive cells of NMDAR1
      increased evidently at 10.0, 20.0 g/m(3) groups (P < 0.05). They were (18.33 +/-
      1.86)%, (64.17 +/- 2.86)% at cerebral cortex, (15.5 +/- 1.87)%, (47.83 +/- 2.16)%
      at hippocampus. The percentages were also elevated obviously in 2, 4, 6 h after
      exposure observation groups. They were (39.07 +/- 3.01)% (70.17 +/- 2.93)% (39.83
      +/- 2.32)% at cerebral cortex, (16.30 +/- 1.03)% (19.80 +/- 1.17)% (16.50 +/-
      1.05)% at hippocampus; Compared with that of 10.0 g/m(3) group, the percentages
      increased significantly only in 4 hr group at hippocampus. CONCLUSION: The
      overactivation of NMDAR1 is the main route by which excitatory amino acids chose
      to join the development of acute intoxicated encephalopathy induced by 1,2-DCE.

PMID- 17456393
TI  - [Effect of human silicotic alveolar macrophages on the expression of the collagen
      type I in human embryonic lung fibroblasts].
AB  - OBJECTIVE: To study the effect of the cultured supernatant of human silicotic
      alveolar macrophages (AM) on the expression of the collagen type I in human
      embryonic lung fibroblasts. METHODS: Human alveolar macrophages were collected
      from a silicotic patient by bronchoalveolar lavage and exposed to silicon dioxide
      for 18 h. Then the cultured supernatant were used to culture human embryonic lung
      fibroblasts for 6 h, 12 h, 18 h, 24 h, 36 h, 48 h, 72 h. Then detected collagen
      anabolism and secretion with (3)H-proline detected the expression of the
      procollagen type I in the fibroblast with immunological method detected the
      quantity of collagen Type I in FB supernatant with Western blot. RESULTS: The
      anabolism and secretion of collagen were increased in cultured supernatant of
      silicotic AM exposed to SiO(2), Along with the time, the expression of collagen
      type I increased. In cultured supernatant of silicotic AM exposed to SiO(2),
      ((3)H-proline: 1096.500 +/- 76.400, 707.000 +/- 62.160, OD: 0.314 +/- 0.011, OD:
      14.218 +/- 0.342. CONCLUSION: SiO(2) may affect the expression of collagen
      through AM mediation and participate in the formation of lung fibrosis.

PMID- 17456394
TI  - [Expressions of collagen in lung of rats exposed to ammonium perchlorate].
AB  - OBJECTIVE: To study the influence on expression of interstitial collagen in lung
      of rats exposed to ammonium perchlorate. METHODS: The rats were treated with AP
      by intratracheal instillation and sacrificed after 3 d, 7 d, 14 d, 28 d. The mRNA
      level of collagen I and collagen III in the lung tissues was measured by RT-PCR.
      RESULTS: The levels of collagen I on 7 d, 14 d, 28 d exposed for high dose group
      (1.93 +/- 0.41, 3.50 +/- 0.90, 2.33 +/- 1.12) and 28 d exposed for medial dose
      group (2.58 +/- 0.86) were higher significant (P < 0.05) than those in negative
      control group (0.52 +/- 0.11, 0.77 +/- 0.15, 0.86 +/- 0.29) The levels of
      collagen I in low dose group exposed for 14 d(1.99 +/- 0.67), 28 d(1.85 +/- 0.67)
      and high dose group 14 d(3.50 +/- 0.90) exposed for 14 d were higher significant
      (P < 0.05) compared to those exposed to AP for 3 d(0.52 +/- 0.14), (1.71 +/-
      0.38). The levels of collagen III on 14 d, 28 d exposed for high dose group (2.60
      +/- 1.00, 1.46 +/- 0.36) and 14 d, 28 d exposed for medial dose group (1.80 +/-
      0.51, 2.16 +/- 0.87) were higher significant (P < 0.05 or P < 0.01) than those in
      negative control group(0.54 +/- 0.20, 0.52 +/- 0.22); The levels of collagen III
      in medial dose group(2.16 +/- 0.87) exposed for 28 d, and high dose group exposed
      for 14 d (2.60 +/- 1.00) were higher significant (P < 0.05) compared to those
      exposed to AP for 3 d(1.22 +/- 0.32, 0.96 +/- 0.17). CONCLUSION: The results
      suggest that AP has a toxic effect to promote the expressions of collagen I and
      collagen III mRNA in lungs of rats, and may be cause fibrosis, but there should
      have more suffice evidences to prove that AP is exactly compound that made lung
      fibrosis.

PMID- 17456395
TI  - [Four patients with hydrogen arsenide poisoning in indium replacement workers].

PMID- 17456396
TI  - [Effects of cadmium on zinc metabolism and its functions in rats].
AB  - OBJECTIVE: To explore the effects of cadmium on zinc metabolism and its function
      and the protective effects of pre-supplement zinc to it. METHODS: NS or different
      doses of CdCl(2) were injected to pregnant dams intraperitoneally at the 7th,
      10th and 13th day of gestation respectively. At the 21st pregnant day embryos
      were taken out from the pregnant rats. Another rats of pre-supplement zinc or no
      pre-supplement zinc group were injected different doses of CdCl(2) or NS
      intraperitoneally after 6 days. After 24 hours the rats were killed. The contents
      of Cd, Zn and relative biomarkers of effect of liver, brain or serum were
      detected in both embryos and adult rats. RESULTS: Compared with control group,
      the contents of T-AOC and Ach were significantly reduced in the Cd treatment
      group in the embryonic brains, the activity of AKP in the embryonic liver tissues
      was decreased, and The Cd content was increased significantly in embryonic liver
      and was negatively correlated with the Zinc content in the embryonic brain. There
      were no differences in the activities of SOD and AKP and the contents of Cd and
      MDA between pre-supplement Zn control group and no supplement Zn control group,
      but higher content of Zn in liver and serum in the former. Compared with no
      supplement Zn control group, there were higher contents of Cd in liver and serum,
      Zn and MDA in liver, lower activities of SOD in liver and AKP in liver and serum,
      and lower content of Zn in serum in the Cd treatment groups. Pre-supplement Zn
      significantly increase the content of Zn and the activities of SOD in liver and
      AKP in serum, decrease the content of MDA in liver and Cd in serum resulted by Cd
      treatment only. The content of Zn and the activity of AKP in serum and the
      activities of SOD and AKP in liver were negatively correlated with the content of
      Cd in corresponding tissue significantly. CONCLUSION: Cadmium can enter embryo
      and enter brain by permeating the brain-blood barrier during the embryonic
      period. The decrease of AKP activity, some neural transmitter and capacity of
      anti-lipid peroxidation that are related with Zn in embryos are caused when the
      pregnant rats are administered with cadmium. Cd can inhibits the activities of
      AKP and SOD in liver, and the activity of AKP in serum respectively, and increase
      the content of MDA in liver dose-dependently. The effects induced by cadmium are
      related with zinc abnormal distribution. Pre-supplement zinc to rats can
      antagonize these effects in different degree.

PMID- 17456397
TI  - [Abnormal liver function associated with occupational exposure to N, N
      dimethylformamide in synthetic leathers works].
AB  - OBJECTIVE: To investigate the hepatotoxic effects of N, N-dimethylformamide (DMF)
      in the workers of a synthetic leathers factory, and the effects on liver function
      of covariates such as alcohol consumption and other factors. METHODS: The workers
      were classified into three groups (low, high and the control) by the
      concentration of DMF in workplace which was determined in the past two years. A
      questionnaire was drawn up for relevant demographic characteristics and other
      factors influencing liver function. The bloods were collected for laboratory test
      which included parameters especially relevant to the liver (ALT AST and gamma
      GT). RESULTS: Low and high-exposure groups were significantly associated with
      elevated ALT and gamma GT, and high-exposure group was significantly associated
      with elevated Liver index. Modeling by stepwise regression analysis demonstrated
      that high concentration of DMF and BMI were associated with and elevated ALT,
      gamma GT and Liver index, besides DMF and BMI, the elevation of ALT was also
      associated with high TRIG. AST was only associated with alcohol consumption. The
      AST/ALT ration < 1 was present in 86.7% of the exposure workers of liver function
      abnormal. CONCLUSION: DMF can cause liver function alternations even if air
      concentration of DMF was below PC-TWA. Besides the levels of DMF exposure,
      obesity (BMI) and alcohol consumption are covariates alternating liver function.
      Liver index can be a parameter for assessment liver function, and the AST/ALT
      ration < 1 may serve as markers of risk in health screening programs.

PMID- 17456398
TI  - [Genetic effects of workers occupationally exposed to mercury using three genetic
      end-points].
AB  - OBJECTIVE: To investigating genetic effects of workers occupationally exposed to
      mercury (Hg). METHODS: The peripheral lymphocytes from 20 workers exposed to
      mercury and 20 controls were measured with micronucleus test, comet assay, hrpt
      gene mutation test and TCR gene mutation test. RESULTS: The mean micronuclei
      rate(MNR) and mean micronucleated cells rate(MCR) in 20 workers were (5.90 +/-
      0.91) per thousand and (5.30 +/- 0.81) per thousand, respectively while MNR and
      MCR in controls were (1.50 +/- 0.47) per thousand and (1.30 +/- 0.31) per
      thousand respectively, The difference of MNR and MCR between workers and controls
      was very significant (P < 0.01). The mean tail length (MTL) of workers and
      controls were (3.16 +/- 0.31) and (0.99 +/- 0.07) microm, respectively. The mean
      tail moment (MTM) of workers and controls were 1.63 +/- 0.22 and 0.39 +/- 0.03,
      respectively, There was a significant difference in MTL and MTM between workers
      and controls(P < 0.01). When the average mutation frequencies (Mfs-hprt) of hprt
      and (Mfs-TCR) of TCR of workers were compared with those of controls, there were
      not significant difference (P > 0.05). CONCLUSION: The results of the
      investigation indicated that the adverse genetic effects in workers
      occupationally exposed to mercury could be detected.

PMID- 17456399
TI  - [Association of the glycophorin A gene mutation in peripheral erythrocytes and
      chronic benzene poisoning].
AB  - OBJECTIVE: To explore the association of the glycophorin A(GPA) gene mutation in
      peripheral erythrocytes and chronic benzene poisoning. METHODS: Sixty-three
      patients with chronic benzene poisonings and 45 benzene-exposed workers who were
      engaged in the same job title were investigated. Fluorescence immunolabeling
      technique and flow cytometry were used to detect GPA mutation frequency in
      peripheral read blood cell. RESULTS: A significant decrease in WBC count and
      neutrophil count was found in patients with chronic benzene poisoning compared
      with control individuals (P<0.01). The WBC count and neutrophil count both
      decreased along with the GPA-NN frequency, and the trends were
      significant(P<0.05).Both WBC counts and neutrophil counts decreased as the
      frequency, and trends were significant(P<0.05). GPA-NN frequency increased along
      with the accumulative exposure score, and the trend was significant (P = 0.0026).
      There was no significant trend between the GPA-Nphi frequency and the
      accumulative exposure score (P = 0.2037). CONCLUSION: A decrease in WBC count and
      neutrophil count is found in patients with chronic benzene poisoning, which can
      arise from genetic damage in bone marrow stem cells, namely gene-duplicating
      mutations (NN) at the GPA locus in bone marrow cells of MN-heterozygous subjects,
      GPA-NN mutagens contributed to the pathogenesis of chronic benzene poisoning.

PMID- 17456400
TI  - [Effects of infrasound on activities of 3beta hydroxysteroid dehydrogenase and
      acid phosphatase of polygonal cells in adrenal cortex zona fasciculate in mice].
AB  - OBJECTIVE: To explore the biological effects of infrasound on the polygonal cells
      in adrenal cortex zona fasciculation in mice. METHODS: The biological effects of
      infrasound on the activities of 3beta hydroxysteroid dehydrogenase (3-betaHSDH)
      and acid phosphatase(ACP) of the polygonal cells in adrenal cortex zona
      fasciculate were observed when exposure to 8 and 16 Hz infrasound at 80, 90, 100,
      110, 120 and 130 dB for 1 day, 7 days and 14 days or 14 days after the exposure.
      RESULTS: When exposure to 8 Hz infrasound, the enzyme activities of 3-betaHSDH
      increase as the sound pressure levels increase. Only when the sound pressure
      levels reach 130 dB, the enzyme activities began to decrease exceptionally. When
      exposure to 16 Hz, 80 dB infrasound, no significant difference between the
      treatment and control group in the activities of 3-betaHSDH could be observed,
      but the injury of the polygonal cells had appeared. When exposure to 16 Hz, 100
      dB infrasound, the activities of 3-betaHSDH started to increase. The cell injury
      still existed. When exposed to 16 Hz, 120 dB infrasound, the local tissue damage
      represented. Fourteen days after the mice exposure to 8 Hz, 90 dB and 130 dB
      infrasound for 14 days continuously, the local tissue injury of the adrenal
      cortex zona fasciculation began to recover at certain extent, but the higher the
      exposure sound pressure level, the poorer the tissue recovery. CONCLUSION: The
      biological effects of infrasound on the polygonal cells in adrenal cortex zona
      fasciculation response to the frequency of the infrasound are found at certain
      action strength range, but this characteristic usually is covered by the severe
      tissue injury. When exposure to infrasound is stopped for a period of time, the
      local tissue injury of the adrenal cortex zona fasciculation could recovers at
      certain extent, but the higher the exposure sound pressure level, the more poorer
      the tissue recovery.

PMID- 17456401
TI  - [Effect of fluoride on expression of telomerase reverse transcriptase expression
      and proliferating cell nuclear antigen in germ cells of rats' testes].
AB  - OBJECTIVE: To study the damages of fluoride on the male reproductive system in
      rat testes. METHODS: A total of 30 male SD rats were randomly divided into
      control group, high, low dose fluorine treated groups, which were given normal
      saline ,20 mg/kg sodium fluoride, and 10mg/kg sodium fluoride respectively. After
      39 days the change of the weight of rats and the number of sperms were observed.
      The change of telomerase reverse transcriptase(TERT) and proliferating cell
      nuclear antigen (PCNA) were observed by using in situ hybridization and
      radioimmunoassay respectively. RESULTS: The weight was (273.39 +/- 20.68),
      (240.00 +/- 21.39) g in NaF treated groups, which was lower than that in control
      group(P < 0.05); The rate of TERT expression in germ cells of testes in NaF
      treated groups was (13.89 +/- 4.86)% and (6.33 +/- 4.42)% respectively, which was
      significantly lower than that in control group (P < 0.05). The rate of PCNA
      expression in germ cells of tests in NaF treated groups was (0.71 +/- 0.05)%,
      (0.60 +/- 0.08)% respectively, which also was significant lower than that in
      control group(P < 0.05). The number of sperms was (18.31 +/- 1.20)10(10)/L, (9.17
      +/- 1.38)10(10)/L, which was lower than that in control group (P < 0.05).
      CONCLUSION: Fluorine possibly damages the male reproductive system by reducing
      the expression of TERT and PCNA.

PMID- 17456402
TI  - [Effects of lead exposure on thymic output naive T cells function].
AB  - OBJECTIVE: To investigate the levels of T cell receptor rearrangement excision
      DNA circles (TRECs) within peripheral blood from workers exposed to lead, and
      thereby to evaluate the number of naive T cells and recent thymic output
      function. METHODS: Quantitative detection of TRECs in peripheral blood
      mononuclear cells (PBMNC) from 10 cases of workers exposed to lead was performed
      by real time PCR analysis. 11 workers without exposure to lead served as
      unexposed controls. In addition, the relationship between TRECs, age, length of
      service, blood lead, urea lead, blood ZPP and urea delta-ALA was investigated.
      RESULTS: The mean value of TRECs in workers exposed to lead was (2.44 +/-
      1.87)/1000 PBMC, significantly under (5.60 +/- 3.96)/1000 PBMC in unexposed
      controls. A significant negative correlation was found between the TRECs and urea
      ALA. But there was no significant correlation between them after controlling for
      blood lead, urea lead. CONCLUSION: Lead exposure may damage thymic output naive T
      cells function. Furthermore, low-level exposure to lead may damage immune system
      and earlier than expected.

PMID- 17456403
TI  - [Effect of intraventricular injection of toluene on learning and memory of mice
      and its mechanism].

PMID- 17456404
TI  - [Effect of Kang Shi Re tablets on contents of neurotensin in hypothalamus of rats
      with heat injury].

PMID- 17456405
TI  - [Survey of morbidity of industrial fluorosis in workers exposed to electrolytic
      aluminum].

PMID- 17456406
TI  - [Separation and determination methods for hexavalent chromium in working places].

PMID- 17456407
TI  - [Determination of p-tert-butyl toluene in air of working places with gas
      chromatography].

PMID- 17456408
TI  - [Determination of blood stibium with atomic fluorescence spectrometry].

PMID- 17456409
TI  - [Nasopharyngeal manifestations and outcomes of acute dimethyl sulfate poisoning].

PMID- 17456410
TI  - [Observation on ocular damage in trichloroethylene-induced medicamentosa like
      dermatitis].

PMID- 17456411
TI  - [Two patients with subacute 1,2-Dichloroethene poisoning].

PMID- 17456412
TI  - [Clinical observation and nursing of lead colic in patients with lead poisoning].

PMID- 17456413
TI  - [Clinical observation and treatment of acute severe dimethyl sulfate poisoning].

PMID- 17456414
TI  - [Explanation for some articles in Law of the People's Republic of China on the
      Prevention and Treatment of Occupational Diseases].

PMID- 17456415
TI  - [Fuzzy mathematics in comprehensive evaluation of occupational risks caused by
      paint spraying work].

PMID- 17456416
TI  - [Anticipating on a synergy between Occupational Health & Safety and Corporate
      Social Responsibility].

PMID- 17456417
TI  - Benefit of liquid crystal moieties in the MIP technique.
AB  - Several liquid crystalline imprinted materials have been synthesized from
      polysiloxanes or polyacrylates bearing mesogenic side-chains and low contents of
      cross-linkers. They were imprinted by various achiral or chiral templates, then
      tested for molecular recognition or assessed as specific catalysts. All mesogenic
      imprinted networks exhibit a much higher affinity towards the template than non
      imprinted networks. On the other hand, the molecular trapping capacity was shown
      to be much greater than that of most of the previously studied non-mesomorphous
      systems. Moreover, it was shown that mesomorphic order provides significant
      enhancement to the bonding between the template and the liquid crystalline
      network and reinforces the shape memory of the imprinted cavities. Some of these
      materials were used to catalyze the isomerization of benzisoxazole. They
      exhibited an acceleration effect close to 100 between imprinted sites and non
      imprinted ones. Lastly, cholesteric networks, that were imprinted by a chiral
      template, showed good properties for the enantiomer separation leading to an
      enantiomeric excess of 35% and a capacity of around 1 mmol g(-1).

PMID- 17456418
TI  - Shape selectivity versus functional group pre-organization in molecularly
      imprinted polymers.
AB  - A systematic survey of related molecular probes differing in shape or functional
      group orientation was used to compare the effects of shape selectivity versus pre
      organization of functional monomers on imprinting and rebinding performance of
      molecularly imprinted polymers (MIPs). These studies revealed that templates with
      two functional group interactions with the MIPs are influenced to a larger degree
      by shape selective interactions than templates with three functional group
      interactions. For example, with two functional group interactions, increasing
      side chain size of compounds 1-5 increased selectivity 5-fold; while the same
      size change for compounds with three functional group interactions leads to a
      maximum 2-fold increase. Thus, the effects of shape selectivity and pre
      organization of functional groups do not appear to work in concert with each
      other during the imprinting process or in the rebinding behavior. Furthermore,
      greater selectivity is generally found for templates with two functional groups,
      where the dominant mode of molecular recognition is shape selectivity. For
      example, the alpha value for the MIP elicited toward template compound 5 with two
      hydrogen bonding groups was 5-12-fold higher than equivalently shaped compounds 6
      8 that have three non-covalent binding interactions (Table 3). On the other hand,
      pre-organization of functional groups dominated the performance of MIPs elicited
      toward templates with three template-functional group interactions. This is
      observed in Tables 6-8, where compounds with identical positioning of three
      functional groups all show less than an order of magnitude change in alpha values
      despite changes in shape.

PMID- 17456419
TI  - Which molecularly imprinted polymer is better?
AB  - Molecularly imprinted polymers (MIP) have been successfully synthesized toward
      many different compounds in the last decades. The mechanistic details of
      selective binding at binding sites are not yet well understood. For this reason
      the characterization of MIP binding has been mostly phenomenological and this
      makes the transfer of results between different laboratories or between different
      types of applications difficult. In this paper we analyze the relationship
      between different types of characterization like isotherms, binding site models,
      chromatographic k and alpha values, etc. as they relate to different applications
      like HPLC, solid phase extraction (SPE), binding assays, batch extraction and
      sensors. It is shown that alpha values determined by elution chromatography
      depend on seemingly irrelevant factors as the length and diameter of the column,
      respectively. The determination of distribution ratios or partition coefficients
      is proposed as an easily understandable and useful quantity in the
      characterization of novel MIPs. Data used for the characterization of a MIP
      should be transferable between different applications but the qualification of
      MIPs as better or worse will depend on the application in case.

PMID- 17456420
TI  - Chromatographic characterisation, under highly aqueous conditions, of a
      molecularly imprinted polymer binding the herbicide 2,4-dichlorophenoxyacetic
      acid.
AB  - The affinity of a 2,4-dichlorophenoxyacetic acid (2,4-D) molecularly imprinted
      polymer (MIP), which was synthesised directly in an aqueous organic solvent, for
      its template (2,4-D) was studied and compared with the affinity exhibited by two
      other reference (control) polymers, NIPA and NIPB, for the same analyte. Zonal
      chromatography was performed to establish the optimal selectivity, expressed as
      imprinting factor (IF), under chromatographic conditions more aqueous than those
      described so far in the literature. Frontal analysis (FA) was performed on
      columns packed with these polymers, using an optimized mobile phase composed of
      methanol/phosphate buffer (50/50, v/v), to extract adsorption isotherm data and
      retrieve binding parameters from the best isotherm model. Surprisingly, the
      template had comparable and strong affinity for both MIP (K = 3.8x10(4) M(-1))
      and NIPA (K = 1.9x10(4) M(-1)), although there was a marked difference in the
      saturation capacities of selective and non-selective sites, as one would expect
      for an imprinted polymer. NIPB acts as a true control polymer in the sense that
      it has relatively low affinity for the template (K = 8.0x10(2) M(-1)). This work
      provides the first frontal chromatographic characterization of such a polymer in
      a water-rich environment over a wide concentration range. The significance of
      this work stems from the fact that the chromatographic approach used is generic
      and can be applied readily to other analytes, but also because there is an
      increasing demand for well-characterised imprinted materials that function
      effectively in aqueous media and are thus well-suited for analytical science
      applications involving, for example, biofluids and environmental water samples.

PMID- 17456421
TI  - Solid phase extraction of food contaminants using molecular imprinted polymers.
AB  - Food contamination from natural or anthropogenic sources poses severe risks to
      human health. It is now largely accepted that continuous exposure to low doses of
      toxic chemicals can be related to several chronic diseases, including some type
      of cancer and serious hormonal dysfunctions. Contemporary analytical methods have
      the sensitivity required for contamination detection and quantification, but
      direct application of these methods on food samples can be rarely performed. In
      fact, the matrix introduces severe disturbances, and analysis can be performed
      only after some clean-up and preconcentration steps. Current sample pre-treatment
      methods, mostly based on the solid phase extraction technique, are very fast and
      inexpensive but show a lack of selectivity, while methods based on immunoaffinity
      extraction are very selective but expensive and not suitable for harsh
      environments. Thus, inexpensive, rapid and selective clean-up methods, relaying
      on "intelligent" materials are needed. Recent years have seen a significant
      increase of the "molecularly imprinted solid phase extraction" (MISPE) technique
      in the food contaminant analysis. In fact, this technique seems to be
      particularly suitable for extractive applications where analyte selectivity in
      the presence of very complex and structured matrices represents the main problem.
      In this review, several applications of MISPE in food contamination analysis will
      be discussed, with particular emphasis on the extraction of pesticides, drugs
      residua, mycotoxins and environmental contaminants.

PMID- 17456422
TI  - Hybrid molecular imprinted membranes having selectivity and separation behavior
      to targeted indole derivatives.
AB  - Molecular imprinted membrane of indole-3-ethanol (IE) was prepared by
      hybridization of IE imprinted polymer powder and polysulfone (PSf) membrane. The
      IE imprinted polymer by covalent imprinting method was synthesized with
      copolymerization of indole-3-ethyl methacrylate (IEMA) and divinylbenzene (DVB).
      The cross-linked P(IEMA-co-DVB) was ground to be powders having less than 63
      microm size and then hybridized within PSf membrane by using phase inversion
      process. The resultant imprinted powder showed binding capacities of 1.8, 7.2, 0
      and 0 micromol g(-1) for IE, indole, 8-hydroxyquinoline and pyrrole in aqueous
      solution, respectively, and after hybridization with the PSf membrane, the value
      was 46, 26, 0 and 0 micromol g(-1). As a result, it was found that the IE
      imprinted powder alone showed non-selectively binding to the IE, but, the
      hybridized powder within the PSf membrane bound selectively the IE. Evidence was
      presented that hydrophobic interaction of the PSf matrix caused the selective and
      efficient binding. We also showed separation behavior of the hybrid membranes and
      discussed on the binding selectivity of the IE molecule. In view point of hybrid
      effect of the PSf membrane and the cross-linked imprinted powder, the results of
      the separation of these substrates were considered.

PMID- 17456423
TI  - Gas phase detection of explosives such as 2,4,6-trinitrotoluene by molecularly
      imprinted polymers.
AB  - Fast, reliable and inexpensive analytical techniques for trace detection of
      explosive components are in high demand. Our approach is to develop specific
      sensor coating materials based on molecularly imprinted polymers (MIPs). Despite
      the known inhibition of radical polymerisations by nitro groups and the known
      shrinkage of the polymer lattice during/after drying we were able to synthesize
      particulate MIPs by suspension polymerisation as well as thin MIP coatings by
      direct surface polymerisation on quartz crystal microbalances (QCM). The best
      method to purify the porous beads was Soxhlet extraction followed by
      supercritical carbon dioxide extraction (SFE with sc-CO2) at mild conditions (150
      bar, 50 degrees C). At least a removal of >99.7% of the template was achieved.
      Performance tests of TNT imprinted polymer beads showed that acrylamide (AA) and
      more pronounced also methacrylic acid (MAA) possessed an enhanced adsorption
      tendency for gaseous TNT. An adsorption of 2,4-DNT, dinitrotoluene, by these MIPs
      was not detected. Using 2,4-DNT as template and methacrylamide, MAAM, a positive
      imprint effect for gaseous 2,4-DNT was achieved with no measurable cross
      sensitivity for 2,4,6-TNT. The thin MIP coatings directly synthesized on the QCMs
      showed thicknesses of 20 to up to 500 nm. Preliminary screening experiments were
      performed for five different monomers and three different solvents (acetonitrile,
      chloroform and dimethylformamide). Best adsorption properties for TNT vapour
      until now showed a PAA-MIP synthesized with chloroform. Direct measurements of
      the mass attachment, respectively frequency decrease of the coated QCMs during
      vapour treatment showed a TNT-uptake of about 150 pg per microg MIP per hour.
      Results look worthy for further studies.

PMID- 17456424
TI  - Enantioseparation on molecularly imprinted monoliths--preparation and adsorption
      isotherms.
AB  - In this paper we report the synthesis of monolithic molecularly imprinted
      polymers (monolithic MIPs) for the chromatographic separation of Z-phenylalanine
      by "in situ" polymerisation. Four different functional monomers were used for the
      preparation and the columns were tested with a standard mobile phase of 1% acetic
      acid in acetonitrile. 4-Vinylpyridine has shown the best separation performance
      with a resolution factor R>1 and was chosen for a further improvement of the
      imprinted stationary phase, which leads to a resolution factor R=2.06. All
      monoliths investigated have surface areas of around 400 m2 g(-1). The columns
      containing 4-vinylpyridine as functional monomer were characterised by frontal
      analysis and peak fitting method. These methods allow the determination of the
      adsorption isotherm which quantify the separation potential of the imprinted
      monoliths.

PMID- 17456425
TI  - Surface plasmon resonance sensor for lysozyme based on molecularly imprinted thin
      films.
AB  - Molecularly imprinted polymers (MIPs) selective for lysozyme were prepared on SPR
      sensor chips by radical co-polymerization with acrylic acid and N,N'
      methylenebisacrylamide. Gold-coated SPR sensor chips were modified with N,N'
      bis(acryloyl)cystamine, on which MIP thin films were covalently conjugated. The
      presence of NaCl during the polymerization and the re-binding tests affected the
      selectivity and the optimization of NaCl concentration in the pre-polymerization
      mixture and the re-binding buffer could enhance the selectivity in the target
      protein sensing. When the lysozyme-imprinted polymer thin films were prepared in
      the presence of 40 mM NaCl, the selectivity factor (target protein
      bound/reference protein bound) of MIP in the re-binding buffer containing 20 mM
      NaCl was 9.8, meanwhile, that of MIP in the re-binding buffer without NaCl was
      1.2. A combination of SPR sensing technology with protein-imprinted thin films is
      a promising tool for the construction of selective protein sensors.

PMID- 17456426
TI  - Dispersive liquid-liquid microextraction followed by high-performance liquid
      chromatography-diode array detection as an efficient and sensitive technique for
      determination of antioxidants.
AB  - Dispersive liquid-liquid microextraction (DLLME) and high performance liquid
      chromatography-diode array detection (HPLC-DAD) was presented for extraction and
      determination of Irganox 1010, Irganox 1076 and Irgafos 168 (antioxidants) in
      aqueous samples. Carbon tetrachloride at microliter volume level and acetonitrile
      were used as extraction and dispersive solvents, respectively. The main
      advantages of method are high speed, high enrichment factor, high recovery, good
      repeatability and extraction solvent volume at microL level. Limit of detection
      for analytes is between 3 and 7 ng mL(-1). One variable at a time optimization
      and response surface modeling were used to obtain optimum conditions for
      microextraction procedure and nearly same experimental conditions were obtained
      using both optimization methods. Recoveries in the ranges 78-86% and 84-110% were
      obtained by one variable at a time and response surface modeling, respectively.
      Using tap water and packed water as matrices do not show any detrimental effect
      on the extraction recoveries and enrichment factors of analytes.

PMID- 17456427
TI  - An improved biosensor for acetaldehyde determination using a bienzymatic strategy
      at poly(neutral red) modified carbon film electrodes.
AB  - Improved biosensors for acetaldehyde determination have been developed using a
      bienzymatic strategy, based on a mediator-modified carbon film electrode and co
      immobilisation of NADH oxidase and aldehyde dehydrogenase. Modification of the
      carbon film electrode with poly(neutral red) mediator resulted in a sensitive,
      low-cost and reliable NADH detector. Immobilisation of the enzymes was performed
      using encapsulation in a sol-gel matrix or cross-linking with glutaraldehyde. The
      bienzymatic biosensors were characterized by studying the influence of pH,
      applied potential and co-factors. The sol-gel and glutaraldehyde biosensors
      showed a linear response up to 60 microM and 100 microM, respectively, with
      detection limits of 2.6 microM and 3.3 microM and sensitivities were 1.7 microA
      mM(-1) and 5.6 microA mM(-1). The optimised biosensors showed good stability and
      good selectivity and have been tested for application for the determination of
      acetaldehyde in natural samples such as wine.

PMID- 17456428
TI  - Analysis of chloroacetanilide herbicides in water samples by solid-phase
      microextraction coupled with gas chromatography-mass spectrometry.
AB  - A solid-phase microextraction (SPME) method has been developed for the
      determination of 3 chloroacetanilide herbicides in both fresh and seawater
      samples. The extracted sample was analyzed by gas chromatography with mass
      spectrometry detection (GC-MS), and parameters affecting SPME operation including
      fibre type, sample pH, sample temperature, mixing speed and extraction time have
      been evaluated and optimized. The amount of dissolved organic matter (DOM) and
      the salt content both affected SPME extraction efficiency, but the presence of
      other competitive extractants such as organochlorine pesticides (OCPs) in the
      matrix showed no insignificance interference. The limit of detection (LOD) for
      acetochlor, metolachlor and butachlor were 1.2, 1.6 and 2.7 ng L(-1),
      respectively. The recoveries for the herbicides ranged from 79 to 102%, and the
      linear dynamic range was from 10 to 1000 ng L(-1). The developed method has been
      used to monitor herbicides contaminations in coastal water samples collected
      around Laizhou bay and Jiaozhou bay in Shandong peninsula, China. The
      concentrations of acetochlor and metolachlor ranged from undetectable to 78.5 ng
      L(-1) and undetectable to 35.6 ng L(-1), respectively. Butachlor was not observed
      but in only one sample and the concentration is lower than the limit of
      quantification (LOQ). The concentrations of the three herbicides in this study
      are low compared to most of the other places reported.

PMID- 17456429
TI  - Chemical composition of contemporary black printing inks based on infrared
      spectroscopy: basic information for the characterization and discrimination of
      artistic prints.
AB  - This article aims to provide the basic information necessary to afford the
      discrimination of artistic prints based on chemical information. The presence of
      original and non-original prints in the art market is a real problem, especially
      for contemporary artists. Most of the non-original elements can be distinguished
      on the basis of their stylistics and printing characteristics, but sometimes this
      information is not enough. To facilitate discrimination in these cases, we
      propose to add, to the previously indicated aspects, the chemical information of
      the materials involved in the production of the original series (inks, paper and
      pencil). Comparison of the composition of any element with that established for
      the original series will permit the attribution of any doubtful element. This
      article is focused on the evaluation of this approach by determining the chemical
      composition of contemporary black printing inks by infrared spectroscopy and by
      searching, on the basis of the information obtained, for criteria capable to
      discriminate between prints made of different inks. The success of the approach
      with this set of inks could easily be extended to the study of colour inks. The
      study also includes the characterization and discrimination of black pigments
      because they are the most characteristic component of these inks and because this
      information can also be useful for other artistic studies. The procedure proposed
      permits the analysis of inks with minimum deterioration of the artwork. Results
      indicate the capability of the approach because, following the procedure, it is
      possible to distinguish between black pigments attending to the presence of
      hydroxyapatite, silicate and some other specific bands, whereas black inks can be
      discriminated by paying attention to the inclusion in their composition of such
      pigments as bone black, Prussian blue, mars brown or other specific bands.
      Scanning electron microscopy analyses have corroborated the results obtained.

PMID- 17456430
TI  - Chemiluminescent studies on the antioxidant activity of amino acids.
AB  - The effect of various concentrations of essential alpha-amino acids on the
      luminol-sodium hypochlorite chemiluminescence (CL) has been studied. It was found
      that all tested compounds have an inhibiting effect. Amino acids with phenolic
      groups present higher inhibition than basic, acidic or neutral amino acids. The
      calculated antioxidant activities by the CL method are compared with those of the
      N,N-diphenyl-picryl hydrazyl (DPPH) method.

PMID- 17456431
TI  - A rapid fluorimetric screening method for the 1,4-benzodiazepines: determination
      of their metabolite oxazepam in urine.
AB  - Oxazepam is the major metabolite screened in urine samples for the evidence of
      the use of benzodiazepine drugs. The methods currently used, however, are
      laborious and time consuming. This paper proposes an oxazepam detection method
      based on its hydrolysis and cyclization--a reaction catalysed by cerium (IV) in
      an ortho-phosphoric acid-containing medium--to form 2-chloro-9(10H)-acridinone, a
      strongly fluorescent molecule. The variables involved in the hydrolysis and
      cyclization stages were optimised. Oxazepam was detectable in the 5-900 ng mL(-1)
      range, with a detection limit of 4.15 ng mL(-1) for k=3. The method was
      successfully used for the determination of oxazepam in urine samples collected at
      different times after the oral administration of Valium and Tranxilium.

PMID- 17456432
TI  - Sensitive determination of ultra-trace nitric oxide in blood using derivatization
      polymer monolith microextraction coupled with reversed-phase high-performance
      liquid chromatography.
AB  - Nitric oxide (NO) plays a very important role in human blood system. In this
      work, a novel approach has been developed for the quantitation of ultra-trace NO
      derivatized with 1,3,5,7-tetramethyl-8-(3',4'-diaminophenyl)-difluoroboradiaza-s
      indacene (DAMBO) using a polymer monolith microextraction (PMME) with a
      poly(methacrylic acid-ethylene glycol dimethacrylate) (MAA-EGDMA) monolith in
      conjunction with high-performance liquid chromatography (HPLC). Both
      derivatization and PMME conditions have been optimized in detail. The detection
      limit of derivatized NO was 2x10(-12) mol L(-1) (signal to noise=3) and linear
      range was 9x10(-11)-4.5x10(-8) mol L(-1). The proposed DAMBO-based derivatization
      PMME-HPLC-fluorescence detection method has been successfully applied for the
      determination of NO in 10 microL blood samples of healthy persons and patients
      suffering from ischemic cardio-cerebrovascular diseases with recoveries varying
      from 87.40 to 91.60%.

PMID- 17456433
TI  - Process monitored spectrophotometric titration coupled with chemometrics for
      simultaneous determination of mixtures of weak acids.
AB  - A new spectrophotometric titration method coupled with chemometrics for the
      simultaneous determination of mixtures of weak acids has been developed. In this
      method, the titrant is a mixture of sodium hydroxide and an acid-base indicator,
      and the indicator is used to monitor the titration process. In a process of
      titration, both the added volume of titrant and the solution acidity at each
      titration point can be obtained simultaneously from an absorption spectrum by
      least square algorithm, and then the concentration of each component in the
      mixture can be obtained from the titration curves by principal component
      regression. The method only needs the information of absorbance spectra to obtain
      the analytical results, and is free of volumetric measurements. The analyses are
      independent of titration end point and do not need the accurate values of
      dissociation constants of the indicator and the acids. The method has been
      applied to the simultaneous determination of the mixtures of benzoic acid and
      salicylic acid, and the mixtures of phenol, o-chlorophenol and p-chlorophenol
      with satisfactory results.

PMID- 17456434
TI  - Simplified Fourier-transform mid-infrared spectroscopy calibration based on a
      spectra library for the on-line monitoring of bioprocesses.
AB  - In order to significantly reduce the time involved in mid-infrared spectroscopy
      calibrations, a novel approach based on a library of pure component spectra was
      developed and tested with an aerobic Saccharomyces cerevisiae fermentation.
      Instead of the 30-50 standards that would have been required to build a
      chemometric model, only five solutions were used to assemble the library, namely
      one for each compound (glucose, ethanol, glycerol, ammonium and acetate).
      Concentration profiles of glucose, ethanol and ammonium were monitored with a
      fair accuracy, leading to standard error of prediction (SEP) values of 0.86, 0.98
      and 0.15 g L(-1). Prediction of the two minor metabolites, acetate and glycerol,
      was less accurate and presented a detection limit of around 0.5 g L(-1). The
      overall performance of the library-based method proved to be very similar to a 49
      standard chemometrics model. The model was shown to be very robust and
      uncorrelated, since it was able to predict accurately the concentration changes
      during a spiking experiment. Even though simple, this method allows more advanced
      calculations, such as determination of the explained variance and detection of
      unexpected compounds using residuals analysis.

PMID- 17456435
TI  - Variation in genome size of argasid and ixodid ticks.
AB  - The suborder Ixodida includes many tick species of medical and veterinary
      importance, but little is known about the genomic characteristics of these ticks.
      We report the first study to determine genome size in two species of Argasidae
      (soft ticks) and seven species of Ixodidae (hard ticks) using flow cytometry
      analysis of fluorescent stained nuclei. Our results indicate a large haploid
      genome size (1C>1000 Mbp) for all Ixodida with a mean of 1281 Mbp (1.31+/-0.07
      pg) for the Argasidae and 2671 Mbp (2.73+/-0.04 pg) for the Ixodidae. The haploid
      genome size of Ixodes scapularis was determined to be 2262 Mbp. We observed inter
      and intra-familial variation in genome size as well as variation between strains
      of the same species. We explore the implications of these results for tick genome
      evolution and tick genomics research.

PMID- 17456436
TI  - The class A chitin synthase gene of Spodoptera exigua: molecular cloning and
      expression patterns.
AB  - Chitin synthase (CHS) is an important enzymatic component required for chitin
      formation in the cuticles and cuticular linings of other tissues. In the present
      study, a new CHS gene was characterized from the beet army worm Spodoptera exigua
      (Hubner) (Se). Homologous alignment and phylogenetic analysis of S. exigua CHS
      (SeCHS) with other related proteins suggest that SeCHS belongs to the class A CHS
      family (SeCHSA). Northern blot analysis revealed that SeCHSA is transcribed
      preferentially in the cuticle and tracheae. Further investigation indicated that
      SeCHSA mRNA is highly expressed in the early and late stages of each larval
      instar, and consistently expressed in high level during the pupal stage. Using
      antibody specific for CHS, SeCHS was further localized in the underlying
      epidermal cells of the integument and tracheal cells, but not in the fat body or
      Malpighian tubules. These data suggest that SeCHS plays an important role in
      cuticle formation and development of S. exigua.

PMID- 17456437
TI  - The unique regulation of Aedes aegypti larval cell ferritin by iron.
AB  - Mosquitoes must blood feed in order to complete their life cycle. The blood meal
      provides a high level of iron that is required for egg development. We are
      interested in developing control strategies that interfere with this process. We
      report the temporal effects of iron exposure on iron metabolism of Aedes aegypti
      larval cells. These cells take up iron in linear relationship to exposure time
      and distribute the iron primarily to the membranes. Iron uptake increases
      cytoplasmic, membrane and secreted ferritin. Membrane ferritin is abundant in
      cells treated with iron, increases in cells in the absence of iron exposure and
      is associated with the secretory pathway. Our data suggest that in contrast to
      mammals, mosquitoes control intracellular iron levels by producing membrane
      ferritin in anticipation of an iron load such as that provided by a blood meal
      and support the hypothesis that secreted ferritin is a primary iron storage
      protein for these animals.

PMID- 17456438
TI  - Drosophila melanogaster Parkin ubiquitinates peanut and septin1 as an E3
      ubiquitin-protein ligase.
AB  - Autosomal recessive juvenile parkinsonism (AR-JP), a common familial form of
      Parkinson's disease, is caused by mutations of human Parkin. To deepen the
      understanding of Parkin biology in an in vivo model of Drosophila, we attempted
      to characterize the function of Drosophila melanogaster Parkin and found that D.
      melanogaster Parkin exhibited UbcH8-dependent E3 ubiquitin-protein ligase
      activity. Using E2 binding and in vitro ubiquitination assays, UbcH8
      preferentially was found to bind to Parkin mutants harboring functional RING1
      domains, but failed to bind to mutants harboring point mutants with complete loss
      of function. This inability of UbcH8 binding to such mutants was accompanied by
      abrogation of an E3 ligase activity, indicating that D. melanogaster Parkin as an
      E3 ligase interacts with UbcH8 through its RING1 domain. An in vivo
      ubiquitination assay revealed that D. melanogaster Parkin existed in
      ubiquitinated form in vivo. Moreover, peanut and septin1, D. melanogaster septin
      proteins, were also ubiquitinated by D. melanogaster Parkin. Co
      immunoprecipitation with membrane protein Syntaxin indicated direct binding of
      septin proteins to syntaxin, implicating their relevance in the exocytosis of
      dopamine in cells. Western blot analysis and DNA fragmentation indicated that the
      rate and efficiency of p53-dependent apoptosis were significantly higher in the
      presence of dopamine than without the septin proteins. Therefore, our findings in
      the present study demonstrate that Parkin possibly influences septin protein
      effects on p53-mediated apoptosis, helping to extend the utility of Drosophila as
      a model system for the study of neurodegeneration.

PMID- 17456439
TI  - Differential modulation of Rhodnius prolixus nitric oxide activities following
      challenge with Trypanosoma rangeli, T. cruzi and bacterial cell wall components.
AB  - Nitric oxide (NO) is a key immune effector and signaling molecule in many
      organisms. However, the contribution NO makes towards insect immunity has
      received little attention, particularly in non-dipteran species. In this study,
      tissue- and time-specific alterations in NO synthase (NOS) gene expression and NO
      production were documented in the hemipteran vector of Chagas' disease, Rhodnius
      prolixus, following in vivo immune challenge by Trypanosoma cruzi, T. rangeli and
      crude bacterial lipopolysaccharide (LPS). The most pronounced reactions to crude
      LPS occurred in major immune tissues (fat body and blood cells), while tissues of
      the digestive tract were most responsive to infections by T. cruzi and T.
      rangeli. The data suggest the NO-mediated immune responses of R. prolixus are
      pathogen-specific and independently modified both at the transcriptional and
      enzyme levels.

PMID- 17456440
TI  - A gamma-glutamyl transpeptidase of Aphidius ervi venom induces apoptosis in the
      ovaries of host aphids.
AB  - Parasitism by the endophagous braconid Aphidius ervi (Hymenoptera, Braconidae)
      has a negative impact on the reproductive activity of its host, Acyrthosiphon
      pisum (Homoptera, Aphididae). The host castration is induced by the parasitoid
      venom and is reproduced by the injection of chromatographic fractions highly
      enriched with two proteins, of 18 (p18) and 36 kDa (p36) in size, respectively.
      Here we demonstrate that these bioactive proteins trigger apoptosis of the cells
      in the germaria and ovariole sheath of the host aphid. Both p18 and p36 were
      internally sequenced and the gathered information was matched against the deduced
      amino acid sequence of the putative proteins encoded by cDNA clones, randomly
      selected from a cDNA library, which was raised using mRNA extracted from A. ervi
      venom glands. The identified cDNA clones contained an insert corresponding to the
      RNA product of an interrupted gene, made of six exons and five introns, which was
      found to be transcribed at higher levels in adult females of A. ervi than in
      males. This gene codes for a putative protein composed of 541 amino acids, with a
      calculated molecular mass of 56.9 kDa, which contained the amino acid sequences
      experimentally determined for both p18 and p36. This putative protein showed a
      significant level of sequence identity with gamma-glutamyl transpeptidases (gamma
      GT), and it was named Ae-gamma-GT. The gamma-GTs are enzymes which play a key
      role in the metabolism of glutathione (GSH) and, as observed in most organisms,
      they are membrane-bound heterodimers formed by a large and a small subunit, which
      originate by post-translational processing of a single-chain precursor. The
      expression in insect cells of Ae-gamma-GT confirmed the occurrence of the
      expected post-translational processing, and demonstrated that, unlike other gamma
      GTs, this protein is secreted in the extracellular environment. A measurable
      gamma-GT activity was detected in the venom of A. ervi and in the chromatographic
      fractions containing Ae-gamma-GT. Thus, we suggest that this venom protein may
      induce apoptosis in the host ovarioles by generating an alteration of the GSH
      metabolism and a consequent oxidative stress.

PMID- 17456441
TI  - Identification and characterization of a new kallikrein-kinin system inhibitor
      from the salivary glands of the malaria vector mosquito Anopheles stephensi.
AB  - A new kallikrein-kinin system inhibitor, designated anophensin, was identified in
      the salivary glands of the malaria vector mosquito, Anopheles stephensi. In vitro
      reconstitution experiments showed that anophensin inhibits activation of the
      kallikrein-kinin system by inhibiting the reciprocal activation of factor XII
      (FXII) and prekallikrein (PK), and subsequent release of bradykinin.
      Additionally, anophensin inhibits activation of the kallikrein-kinin system on
      cultured human umbilical vein endothelial cells (HUVECs). Direct binding assays
      show that this inhibitory effect is due to Zn(2+)-dependent specific binding of
      anophensin to both FXII and high molecular weight kininogen (HK). Furthermore,
      anophensin interacts with both the N-terminus of FXII and domain D5 of HK, which
      are the binding domains for biological activating surfaces. These results suggest
      that anophensin inhibits activation of the kallikrein-kinin system by interfering
      with the association of FXII and HK with biological activating surfaces,
      resulting in the inhibition of bradykinin release in a host animal during insect
      blood-feeding.

PMID- 17456442
TI  - Regulation of phenoloxidase activity by high- and low-molecular-weight inhibitors
      from the larval hemolymph of Manduca sexta.
AB  - Insect phenoloxidases (POs) generate quinones and other reactive intermediates to
      immobilize and kill invading pathogens and parasites. Due to the presumed
      cytotoxicity of these compounds, PO activity and its proteolytic activation have
      to be regulated as a local, transient reaction against nonself in order to
      minimize damage to the host tissues and cells. We identified a Manduca sexta cDNA
      encoding a polypeptide sequence with its carboxyl-terminal 33 residues similar to
      the housefly phenoloxidase inhibitor (POI). The recombinant POI, secreted into
      the Escherichia coli periplasmic space along with its fusion partner DsbC, was
      released by osmotic shock and isolated by nickel affinity chromatography.
      Following enterokinase digestion and protein separation, the POI was purified to
      near homogeneity in a soluble form which inhibited M. sexta PO at a high
      concentration. We then produced the inhibitor using a modified baculovirus-insect
      cell system and isolated the glycoprotein from the conditioned medium.
      Deglycosylation coupled with inhibition assay revealed that O-glycosylation only
      moderately increased its inhibitory activity. While this led us to speculate the
      role of Tyr(64) hydroxylation, we were unable to modify the recombinant protein
      with tyrosine hydroxylase or purify M. sexta POI (Tyr(64)dopa) from the larval
      plasma. Instead, we isolated a low-M(r), heat-stable compound which strongly
      inhibited PO. The wavelength of maximum absorbance is 257 nm for the inhibitor.
      These data suggest that the down-regulation of PO activity in M. sexta is
      achieved by two mechanisms at least.

PMID- 17456443
TI  - Studies on middle and posterior silk glands of silkworm (Bombyx mori) using two
      dimensional electrophoresis and mass spectrometry.
AB  - Silk glands, present in the larval stage of the silkworm, produce threads of
      silky material to form the cocoon and are mainly composed of three parts: the
      anterior, the middle, and the posterior silk glands, each playing different roles
      in silk secretion. High-resolution two-dimensional polyacrylamide gel
      electrophoresis and computer-assisted analysis were used to investigate
      quantitative and qualitative differences between the middle and posterior silk
      glands. Silver staining revealed over 600 spots for each sample, mostly
      distributed from 15 to 100 kDa with pH 4-7. Computer-assisted image analysis,
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry, and
      post-source decay technology suggested that there were significant differences in
      spot distribution and expression between the middle and posterior silk glands. In
      addition, 98 spots from the posterior silk gland were excised and further
      investigated following trypsin digestion. The results suggested that more than
      20% of the 88 proteins identified were related to heat-shock proteins and
      chaperones. Redox system and DNA replication proteins involved in silk protein
      synthesis were also detected in the posterior silk gland. Interestingly, two
      novel serpin proteins were identified in the middle silk gland, and to a lesser
      extent in the posterior gland, which were presumed to be involved in regulation
      of proteolytic activity and protection of silk proteins from degradation.

PMID- 17456444
TI  - Molecular cloning and developmental expression of the gene encoding juvenile
      hormone esterase in the yellow-spotted longicorn beetle, Psacothea hilaris.
AB  - Juvenile hormone (JH) plays a key role in the regulation of growth, development,
      diapause and reproduction in insects. The regulation of JH titers in the insect
      body is therefore crucial throughout postembryonic development. One of the major
      pathways of JH metabolism is degradation by a highly selective enzyme, juvenile
      hormone esterase (JHE). We obtained a full-length cDNA encoding JHE in Psacothea
      hilaris (PhJHE). The complete PhJHE cDNA sequence is comprised of 1989 bp with an
      open reading frame of 1785 bp encoding 595 amino acid residues. The deduced
      protein sequence of PhJHE showed high homology with the Tenebrio molitor JHE (50%
      amino acid identity) and moderate homology with the Drosophila melanogaster JHE
      (34%). The PhJHE transcript was expressed mainly in the fat body. PhJHE
      transcript levels were low until day 3 of the 5th (final) larval instar, then
      steadily increased reaching a peak on day 13 (the prepupa stage), coinciding well
      with the peak hemolymph enzyme activity level. Sustained starvation of larvae
      after a period of feeding stimulated the expression of PhJHE mRNA while feeding
      the larvae with glucose downregulated its expression. These results are discussed
      with reference to the induction of precocious metamorphosis in this beetle by
      starvation.

PMID- 17456445
TI  - Identification of crinosterol from astigamatid mites.
AB  - A 24-alkylsterol, crinosterol [(24S)-24-methylcholesta-5,22(E)-dien-3beta-ol] has
      been isolated from sea-dwelling animals, protists and plants. Here, we identified
      crinosterol from nine species of mites (Acari). The compound was identified by
      using (1)H-NMR analysis and GCMS spectral data along with the HPLC retention time
      by comparing with those of the synthesized compound. As far as we know, this is
      the first report on the identification of crinosterol from arthropods.
      Furthermore, after Rhizoglyphus robini were fed on artificial diets with d(3)
      methionine, d(2)-crinosterol was detected from the mite's extracts. The
      incorporation of two deuterium atoms into the sterol indicated that a d(3)-methyl
      group was introduced into the C24 of the side chain to form crinosterol. Although
      the details of the biosynthesis of crinosterol remain unknown, the discovery of
      crinosterol in the mites implies the existence of interesting sterol metabolisms
      in the animals.

PMID- 17456446
TI  - Evaluating the insecticide resistance potential of eight Drosophila melanogaster
      cytochrome P450 genes by transgenic over-expression.
AB  - In Drosophila melanogaster, the increased expression of Cyp6g1 results in
      resistance to chemically unrelated insecticides including DDT, neonicotinoids and
      insect growth regulator insecticides. To determine the insecticide resistance
      capacity of other D. melanogaster cytochrome P450s, we used the GAL4/UAS system
      to express individual P450s in the midgut, Malpighian tubules and fat body of
      transgenic flies. Drosophila over-expressing Cyp6g1, Cyp6g2, Cyp6t3, Cyp6a2,
      Cyp6a8, Cyp6a19, Cyp6a23 and Cyp12d1 were screened for resistance to four
      insecticides--DDT, nitenpyram, dicyclanil and diazinon. Increased survival on
      insecticides is detected for Cyp6g1 (DDT, nitenpyram and dicyclanil), Cyp6g2
      (nitenpyram and diazinon) and Cyp12d1 (DDT and dicyclanil) over-expression lines.
      No increased survival on any insecticide was detected for flies over-expressing
      either Cyp6a2, Cyp6a8, Cyp6t3, Cyp6a19 or Cyp6a23.

PMID- 17456447
TI  - Costly steroids: egg testosterone modulates nestling metabolic rate in the zebra
      finch.
AB  - The transfer of non-genetic resources from mother to the offspring often has
      considerable consequences for offspring performance. In birds, maternally derived
      hormones are known to influence a variety of morphological, physiological and
      behavioural traits in the chick. So far, the range of these hormonal effects
      involves benefits in terms of enhanced growth and competitive ability as well as
      costs in terms of immunosuppression. However, since yolk hormones can enhance
      growth and begging activity, high levels of these hormones may also involve
      energetic costs. Here, we show experimentally that elevated levels of prenatal
      testosterone increase resting metabolic rate in nestling zebra finches
      (Taeniopygia guttata). Surprisingly, however, elevation of prenatal testosterone
      did not result in higher growth rates and, thus, differences in resting
      metabolism do not seem to be linked to nestling growth. We conclude that apart
      from immunosuppressive effects, high levels of egg steroids may also entail costs
      in terms of increased energy expenditure.

PMID- 17456448
TI  - An increase in pH boosts olfactory communication in sticklebacks.
AB  - Human-induced eutrophication is a serious environmental problem that constrains
      visual communication and influences the mate choice process in fishes.
      Eutrophication also changes the chemical environment and the pH of the water,
      which could influence the use of olfactory cues in mate choice. Here, we show
      that an increase in pH enhances the use of male olfactory cues in mate choice in
      three-spined sticklebacks, Gasterosteus aculeatus. In a laboratory choice
      experiment, gravid females were more attracted to male olfactory cues when pH was
      raised. This could compensate for impaired visual communication in eutrophied
      waters and facilitate adaptive mate choice.

PMID- 17456449
TI  - Daytime noise predicts nocturnal singing in urban robins.
AB  - Ambient noise interferes with the propagation of acoustic signals through the
      environment from sender to receiver. Over the past few centuries, urbanization
      and the development of busy transport networks have led to dramatic increases in
      the levels of ambient noise with which animal acoustic communications must
      compete. Here we show that urban European robins Erithacus rubecula, highly
      territorial birds reliant on vocal communication, reduce acoustic interference by
      singing during the night in areas that are noisy during the day. The effect of
      ambient light pollution, to which nocturnal singing in urban birds is frequently
      attributed, is much weaker than that of daytime noise.

PMID- 17456450
TI  - The canine distemper epidemic in Serengeti: are lions victims of a new highly
      virulent canine distemper virus strain, or is pathogen circulation stochasticity
      to blame?
AB  - In the year 1994, the Serengeti lion population was decimated by a canine
      distemper disease outbreak. Retrospective investigations showed that this host
      population had already been in contact with the pathogen in 1981 without any
      detected sign of disease. As an alternative to the virus mutation hypothesis to
      explain this difference in virulences observed in 1981 and 1994, we propose a
      novel mechanism of disease emergence based on variation in population immunity.
      We use a stochastic model to show that stochastic fluctuations in pathogen
      circulation, owing to a low probability of virus transmission from its reservoir
      to the target host and thereby resulting in variations in the global immunity
      level of the target host population, can explain the observations made in
      Serengeti. This mechanism may also be involved in other infectious disease
      emergences or re-emergences.

PMID- 17456451
TI  - A short term benefit for outcrossing in a Daphnia metapopulation in relation to
      parasitism.
AB  - Because host-parasite interactions are often specific to the host and parasite
      genotype, it may be important whether a host reproduces by selfing or
      outcrossing. The latter is associated with higher genetic diversity among the
      offspring and may reduce parasite success. Here, we test whether outbred
      offspring of Daphnia magna have an advantage over selfed offspring in the
      presence of a parasite transmitted from mothers to offspring. Using outdoor
      mesocosms, we set up monoclonal and polyclonal host populations of D. magna
      infected with a prevalence of 100% with the horizontally and vertically
      transmitted microsporidian parasite Octosporea bayeri. These populations
      diapaused after sexual reproduction and hatchlings were screened for signs of O.
      bayeri. Parasite prevalence was 98.9% for hatchlings from the monoclonal
      treatment, but only 85.2% among the hatchlings from the polyclonal populations,
      indicating a short-term benefit for outbreeding. This benefit occurs, we
      hypothesize, not owing to inbreeding depression, but because the vertically
      transmitted parasite is less able to establish itself in the relatively new
      genetic environment of the outbred offspring, as compared to the more stable
      environment when transmitted to selfed offspring. To quantify the fitness
      consequences of this 14% prevalence difference, we studied the within-season
      epidemiology of O. bayeri, using an epidemiological model. We then examined
      whether descendants of outbred offspring produce more resting eggs than the
      descendants of selfed offspring. The data and our model show that Daphnia which
      are uninfected at the beginning of the growth season have a large advantage when
      the entire season is considered. Our data support the Red Queen hypothesis which
      states that in the presence of coevolving parasites, outbreeding is favoured in
      the host.

PMID- 17456452
TI  - Anti-predator defence and the complexity-stability relationship of food webs.
AB  - The mechanism for maintaining complex food webs has been a central issue in
      ecology because theory often predicts that complexity (higher the species
      richness, more the interactions) destabilizes food webs. Although it has been
      proposed that prey anti-predator defence may affect the stability of prey
      predator dynamics, such studies assumed a limited and relatively simpler
      variation in the food-web structure. Here, using mathematical models, I report
      that food-web flexibility arising from prey anti-predator defence enhances
      community-level stability (community persistence and robustness) in more complex
      systems and even changes the complexity-stability relationship. The model
      analysis shows that adaptive predator-specific defence enhances community-level
      stability under a wide range of food-web complexity levels and topologies, while
      generalized defence does not. Furthermore, while increasing food-web complexity
      has minor or negative effects on community-level stability in the absence of
      defence adaptation, or in the presence of generalized defence, in the presence of
      predator-specific defence, the connectance-stability relationship may become
      unimodal. Increasing species richness, in contrast, always lowers community-level
      stability. The emergence of a positive connectance-stability relationship however
      necessitates food-web compartmentalization, high defence efficiency and low
      defence cost, suggesting that it only occurs under a restricted condition.

PMID- 17456453
TI  - Optics of the ultraviolet reflecting scales of a jumping spider.
AB  - The jumping spider Cosmophasis umbratica from Singapore is strongly sexually
      dimorphic. The males, but not the females, reflect ultraviolet as well as green
      orange light. The scales responsible for this are composed of a chitin-air-chitin
      sandwich in which the chitin layers are three-quarters of a wavelength thick and
      the air gap a quarter wavelength (where lambda=600 nm, the peak wavelength of the
      principal reflection maximum). It is shown that this configuration produces a
      second reflectance peak at approximately 385 nm, accounting for the observed
      reflection in the ultraviolet. Other scales have a similar thickness of chitin
      but lack the air gap and thus produce a dull purple reflection. This novel
      mechanism provides the spiders with two colour signals, both of which are
      important in mating displays.

PMID- 17456454
TI  - Subordinate male meerkats prospect for extra-group paternity: alternative
      reproductive tactics in a cooperative mammal.
AB  - In cooperatively breeding species, subordinates typically suffer strong
      constraints on within-group reproduction. While numerous studies have highlighted
      the additional fitness benefits that subordinates might accrue through helping,
      few have considered the possibility that subordinates may also seek extra-group
      matings to improve their chances of actually breeding. Here, we show that
      subordinate males in cooperative meerkat, Suricata suricatta, societies conduct
      frequent extraterritorial forays, during periods of peak female fertility, which
      give rise to matings with females in other groups. Genetic analyses reveal that
      extra-group paternity (EGP) accrued while prospecting contributes substantially
      to the reproductive success of subordinates: yielding the majority of their
      offspring (approx. 70%); significantly reducing their age at first reproduction
      and allowing them to breed without dispersing. We estimate that prospecting
      subordinates sire 20-25% of all young in the population. While recent studies on
      cooperative birds indicate that dominant males accrue the majority of EGP, our
      findings reveal that EGP can also arise from alternative reproductive tactics
      employed exclusively by subordinates. It is important, therefore, that future
      attempts to estimate the fitness of subordinate males in animal societies
      quantify the distribution of extra-group as well as within-group paternity,
      because a substantial proportion of the reproductive success of subordinates may
      otherwise go undetected.

PMID- 17456456
TI  - Fidelity and over-wintering of sea turtles.
AB  - While fidelity to breeding sites is well demonstrated in marine turtles, emerging
      knowledge of migratory routes and key foraging sites is of limited conservation
      value unless levels of fidelity can be established. We tracked green (Chelonia
      mydas, n=10) and loggerhead (Caretta caretta, n=10) turtles during their post
      nesting migration from the island of Cyprus to their foraging grounds. After
      intervals of 2-5 years, five of these females were recaptured at the nesting
      beach and tracked for a second migration. All five used highly similar migratory
      routes to return to the same foraging and over-wintering areas. None of the
      females visited other foraging habitats over the study period (units lasted on
      average 305 days; maximum, 1356 days), moving only to deeper waters during the
      winter months where they demonstrated extremely long resting dives of up to 10.2h
      (the longest breath-holding dive recorded for a marine vertebrate). High levels
      of fidelity and the relatively discrete nature of the home ranges demonstrate
      that protection of key migratory pathways, foraging and over-wintering sites can
      serve as an important tool for the future conservation of marine turtles.

PMID- 17456455
TI  - Evidence of ancient DNA reveals the first European lineage in Iron Age Central
      China.
AB  - Various studies on ancient DNA have attempted to reconstruct population movement
      in Asia, with much interest focused on determining the arrival of European
      lineages in ancient East Asia. Here, we discuss our analysis of the mitochondrial
      DNA of human remains excavated from the Yu Hong tomb in Taiyuan, China, dated
      1400 years ago. The burial style of this tomb is characteristic of Central Asia
      at that time. Our analysis shows that Yu Hong belonged to the haplogroup U5, one
      of the oldest western Eurasian-specific haplogroups, while his wife can be
      classified as haplogroup G, the type prevalent in East Asia. Our findings show
      that this man with European lineage arrived in Taiyuan approximately 1400 years
      ago, and most probably married a local woman. Haplogroup U5 was the first west
      Eurasian-specific lineage to be found in the central part of ancient China, and
      Taiyuan may be the easternmost location of the discovered remains of European
      lineage in ancient China.

PMID- 17456457
TI  - Genetic isolation of a now extinct population of bottlenose dolphins (Tursiops
      truncatus).
AB  - A number of dolphin species, though highly mobile, show genetic structure among
      parapatric and sometimes sympatric populations. However, little is known about
      the temporal patterns of population structure for these species. Here, we apply
      Bayesian inference and data from ancient DNA to assess the structure and dynamics
      of bottlenose dolphin (Tursiops truncatus) populations in the coastal waters of
      the UK. We show that regional population structure in UK waters is consistent
      with earlier studies suggesting local habitat dependence for this species in the
      Mediterranean Sea and North Atlantic. One genetically differentiated UK
      population went extinct at least 100 years ago and has not been replaced. The
      data indicate that this was a local extinction, and not a case of historical
      range shift or contraction. One possible interpretation is a declining
      metapopulation and conservation need for this species in the UK.

PMID- 17456458
TI  - Altered reproductive success in rat pairs after environmental-like exposure to
      xenoestrogen.
AB  - Endocrine-disrupting compounds (EDCs) have the capacity of altering the normal
      function of the endocrine system. EDCs have shown dramatic effects on the
      reproductive biology of aquatic wildlife and may affect human reproduction as
      well. Studies on EDCs in mammalian species have often investigated the effects of
      short-term, high doses on male and female reproductive physiology. However, it is
      difficult to predict from such studies the effects of EDC on populations that are
      exposed to very low doses throughout their life via contaminated food and water.
      We studied the effects of EDC on mammalian reproduction with an environmental
      like protocol where the endpoint is the reproductive success of exposed pairs. We
      focused on a subclass of EDC, the xenoestrogens, which mimic the action of
      natural oestrogen hormones. Male and female rats were exposed to low doses of the
      pure oestrogen, ethynyloestradiol, during development, by oral administration to
      their mothers during pregnancy and lactation, and to them until puberty. We
      evaluated the effects of the exposure on development and reproductive physiology
      of individuals, and on fertility and fecundity of pairs in which both members had
      been exposed to the same treatment. We found that low doses caused major
      reproductive deficits in the experimental animals. Very low, environmentally
      relevant doses did not have evident effects on exposed animals; however, the
      fecundity of exposed pairs was substantially altered. Environmentally relevant
      doses of xenoestrogens which have no evident physiological effects can alter the
      reproductive success of exposed pairs in natural populations.

PMID- 17456459
TI  - Why do men marry and why do they stray?
AB  - Humans are quite unusual compared to other great apes in that reproduction
      typically takes place within long-term, iteroparous pairings--social arrangements
      that have been culturally reified as the institution of marriage. With respect to
      male behaviour, explanations of marriage fall into two major schools of thought.
      One holds that marriage facilitates a sexual division of labour and paternal
      investment, both important to the rearing of offspring that are born helpless and
      remain dependent for remarkably long periods (provisioning model). And the other
      suggests that the main benefits which men receive from entering into marriage
      derive from monopolizing access to women's fertility (mating effort model). In
      this paper, we explore extramarital sexual relationships and the conditions under
      which they occur as a means of testing predictions derived from these two models.
      Using data on men's extramarital sexual relationships among Tsimane forager
      horticulturists in lowland Bolivia, we tested whether infidelity was more common
      when men had less of an opportunity to invest in their children or when they
      risked losing less fertility. We found that Tsimane men appear to be biasing the
      timing of their affairs to when they are younger and have fewer children,
      supporting the provisioning model.

PMID- 17456460
TI  - Predicting unknown species numbers using discovery curves.
AB  - A common approach to estimating the total number of extant species in a taxonomic
      group is to extrapolate from the temporal pattern of known species descriptions.
      A formal statistical approach to this problem is provided. The approach is
      applied to a number of global datasets for birds, ants, mosses, lycophytes,
      monilophytes (ferns and horsetails), gymnosperms and also to New World grasses
      and UK flowering plants. Overall, our results suggest that unless the inventory
      of a group is nearly complete, estimating the total number of species is
      associated with very large margins of error. The strong influence of
      unpredictable variations in the discovery process on species accumulation curves
      makes these data unreliable in estimating total species numbers.

PMID- 17456461
TI  - The impact of lifestyle risk factors on female infertility.
AB  - BACKGROUND: Over 2 million couples in the United States are infertile. The
      literature reflects a number of potential lifestyle risks that have been
      associated with the development of this condition; however, few studies have
      investigated these risks concurrently. With knowledge of the importance of
      behavioral threats to fertility, women's health care providers will be in a
      better position to screen and assist women to modify their fertility risks.
      OBJECTIVES: The objectives of this study were (1) to identify lifestyle factors
      associated with infertility in women by comparing a sample of infertile women
      with a group of fertile women and (2) to offer recommendations to women's health
      providers, on counseling women at risk for infertility. METHODS: A re-examination
      of the 1995 National Survey of Family Growth (NSFG) allowed for the investigation
      of lifestyle factors associated with infertility in women. Using a conceptual
      model of health behavior to guide the selection of variables, together with
      multiple logistic regression techniques, an explanatory model of infertility was
      estimated on a sample of 824 women between the ages of 16 and 45 years. RESULTS:
      Factors directly related to infertility included increasing age, a history of an
      ectopic pregnancy, current smoking, obesity, and self reported health status.
      Protective effects were associated with a history of condom use and having had a
      Pap smear in the last year. CONCLUSIONS AND IMPLICATIONS: Routine well-women
      visits offer an excellent opportunity to begin to address the impact of selected
      risk factors for infertility. Clinicians can utilize these visits to target
      appropriate interventions for initiating, repeating, and reinforcing messages on
      fertility risk.

PMID- 17456462
TI  - Psychosocial and reported inflammatory disease correlates of self-reported heart
      disease in women from South of Israel.
AB  - BACKGROUND: Past and recent research suggests that psychological and biological
      factors may increase women's risk of coronary heart disease (CHD). This study
      examined the prevalence and correlates of self-reported heart disease among
      Jewish women from the Negev, a socio-economically and culturally unique region in
      south of Israel. METHOD: A cross-sectional design was used. We interviewed over
      the phone 526 randomly-selected women (mean age: 44.3+/-14.2 years) about
      background variables (e.g., education), biomedical risk factors (e.g., body mass
      index or BMI), self-reported inflammatory diseases (rheumatoid arthritis or RA,
      urinary infections), psychosocial factors (depression, hopelessness, self-esteem,
      social-support) and self-rated health and heart disease. RESULTS: Prior physician
      diagnosis of heart disease was reported by 8.2% of women. Age, economic
      difficulties, diabetes, hypertension, BMI, physical exercise, RA and urinary
      infections were significantly associated with reported heart disease. Of all
      psychosocial factors considered, hopelessness and self-esteem significantly
      distinguished heart disease cases from non-cases. In a multiple logistic
      regression, poor self-esteem, RA and hypertension were significant independent
      correlates of self-reported heart disease. CONCLUSIONS: Pending replication with
      objective measures of heart disease and a prospective design, poor self-esteem
      and RA may prove to be new CHD risk factors in women.

PMID- 17456463
TI  - Native Hawaiian women and the experience of breast cancer.
AB  - This article describes a qualitative inquiry into the experiences of Native
      Hawaiian women living through and beyond a diagnosis of breast cancer. Native
      Hawaiian women have increased incidence and mortality breast cancer rates
      compared with other ethnic groups in Hawaii. Health promotion programs targeted
      at Native Hawaiians have often failed because of cultural inappropriateness. A
      lack of knowledge about the culture is frequently a part of this failure.
      Therefore, the specific purpose of this study was to examine the lived experience
      of a selected group of Native Hawaiian breast cancer survivors, uncover the
      connections between their narratives and their personal and cultural milieux, and
      generate knowledge about the Native Hawaiian woman's breast cancer experience
      that would be useful in planning future health promotion outreach efforts. The
      study consisted of interview data collected from 11 Native Hawaiian female
      participants, ranging from 44 to 82 years of age. An interpretive
      phenomenological analysis of the data identified recurrent contexts and themes.
      The three major contexts in their stories were discovery, transformation
      (physical, emotional and spiritual), and life realignment. Themes included the
      importance of spiritual connection, an altruistic desire to reach out and assist
      others in a similar situation, and a context of familial silence about cancer
      history. These elements can assist in formulating health promotion and
      intervention activities for this population. Interwoven with these themes was the
      Native Hawaiian concept of pono--a sense of rightness and balance, and the
      crucial importance of the participants' Native Hawaiian identity and cultural
      heritage.

PMID- 17456464
TI  - Adherence among women with HIV infection in Puerto Rico: the potential use of
      modified directly observed therapy (MDOT) among pregnant and postpartum women.
AB  - Women are the fastest growing segment of the adult population acquiring HIV, and
      most women infected with HIV are in their reproductive years. The success of
      HAART is highly dependent upon the ability and willingness of the individual to
      adhere to complex antiretroviral regimens. Improved adherence among HIV-infected
      pregnant women will delay disease progression in the mother and should also
      reduce HIV transmission to the baby. Modified directly observed therapy (MDOT),
      may benefit this population. MDOT has been shown to be an acceptable and feasible
      intervention among HIV substance users; however, no-one has yet evaluated the use
      of MDOT in pregnant and postpartum women. Based on semi-structured interviews
      with 17 Latina women with HIV infection, we explored women's adherence patterns
      and barriers to adherence and their perceptions of a hypothetical MDOT program.
      The vast majority of women positively appraised the MDOT program as an effective
      means to increase and reinforce adherence to demanding drug regimens. Respondents
      cited the face-to-face contact, the supportive nature of the relationship, and
      the practical approach of the program as the primary reasons for the
      effectiveness of MDOT. Results indicate that MDOT could be an acceptable
      intervention for pregnant and postpartum Latina women to improve adherence to
      HAART.

PMID- 17456465
TI  - Maternal fear associated with pregnancy and childbirth in Hong Kong Chinese
      women.
AB  - BACKGROUND: Women's fear toward pregnancy and childbirth is a common and
      important health concern. This study examined the objects, causes, and
      manifestations of maternal fears and their associated demographic factors in a
      sample of Hong Kong Chinese pregnant women. METHODS: Three hundred Chinese
      pregnant women were recruited in an obstetric unit in Hong Kong in 2003. Data
      were collected using a 73-item questionnaire. Principal components factor
      analysis was applied to identify the objects, causes, and manifestations of fear
      toward pregnancy and childbirth. RESULTS: The mean maternal age was 30 (SD 5.6)
      years. All participants reported some degree of fear. The main objects of fear
      were "fear of childbirth" and "child's and mother's wellbeing." The first factor
      identified for causes of fear was "negative stories," followed by "negative
      attitude or mood." Regarding the various manifestations of fear, "stress
      symptoms" and "wish to avoid pregnancy and childbirth" ranked highest. Twenty-two
      percent of participants had considered requesting an elective cesarean section
      due to fear of childbirth. CONCLUSIONS: Even in a group of low-risk pregnant
      women, fear toward pregnancy and childbirth was frequently experienced. Better
      strategies to address women's psychological needs during pregnancy are warranted.

PMID- 17456466
TI  - Impact of drug market changes on substance-using pregnant women in three key
      Sydney drug markets.
AB  - INTRODUCTION: In 2001 the supply of heroin was substantially reduced across
      Australia. Given the child protection concerns associated with the use of
      substances by pregnant women, it was pertinent to examine how the reduction in
      the supply of heroin affected this community of users. This paper aimed to assess
      the extent of any drug-related problems among pregnant women associated with the
      reduction in heroin supply in New South Wales (NSW). METHOD: Two sources of data
      were used: (1) Data on hospital visits in NSW in which drug and alcohol problems
      were noted as complicating the pregnancy; and (2) Key informant reports from
      services targeting substance-using pregnant women across the three main Sydney
      drug markets. RESULTS: The shortage did not affect the number of hospital
      separations for substance-using pregnant women, nor the number of women referred
      to services for substance use in pregnancy. Key informants reported an increase
      in the use of cocaine among pregnant women and a change in injection sites for
      some women (including into breast tissue). No substantial change in adverse
      outcomes was observed to be associated with this change in patterns of drug use.
      DISCUSSION: The reduction in heroin supply appeared to have limited impact on the
      number of substance-using pregnant women as assessed by hospital episodes and key
      informant reports. The evidence suggested an increase in the injecting of cocaine
      by pregnant women using drug treatment services, similar to the changes in drug
      use patterns observed among other groups of injecting drug users. The lack of
      change observed in the qualitative and statistical data regarding adverse health
      consequences associated with cocaine injecting suggests the potentially negative
      impact of maternal cocaine use on infant health may be difficult to detect and
      monitor.

PMID- 17456468
TI  - The plant homeodomain fingers of fission yeast Msc1 exhibit E3 ubiquitin ligase
      activity.
AB  - The DNA damage checkpoint pathway governs how cells regulate cell cycle
      progression in response to DNA damage. A screen for suppressors of a fission
      yeast chk1 mutant defective in the checkpoint pathway identified a novel
      Schizosaccharomyces pombe protein, Msc1. Msc1 contains 3 plant homeodomain (PHD)
      finger motifs, characteristically defined by a C4HC3 consensus similar to RING
      finger domains. PHD finger domains in viral proteins and in the cellular protein
      kinase MEKK1 (mitogen-activated protein kinase/extracellular signal-regulated
      kinase kinase kinase 1) have been implicated as ubiquitin E3 protein ligases that
      affect protein stability. The close structural relationship of PHD fingers to
      RING fingers suggests that other PHD domain-containing proteins might share this
      activity. We show that each of the three PHD fingers of Msc1 can act as ubiquitin
      E3 ligases, reporting for the first time that PHD fingers from a nuclear protein
      exhibit E3 ubiquitin ligase activity. The function of the PHD fingers of Msc1 is
      needed to rescue the DNA damage sensitivity of a chk1Delta strain. Msc1 co
      precipitates Rhp6, the S. pombe homologue of the human ubiquitin-conjugating
      enzyme Ubc2. Strikingly, deletion of msc1 confers complete suppression of the
      slow growth phenotype, UV and hydroxyurea sensitivities of an rhp6 deletion
      strain and restores deficient histone H3 methylation observed in the rhp6Delta
      mutant. We speculate that the target of the E3 ubiquitin ligase activity of Msc1
      is likely to be a chromatin-associated protein.

PMID- 17456469
TI  - N-terminal tyrosine modulation of the endocytic adaptor function of the beta
      arrestins.
AB  - The highly homologous beta-arrestin1 and -2 adaptor proteins play important roles
      in the function of G protein-coupled receptors. Either beta-arrestin variant can
      function as a molecular chaperone for clathrin-mediated receptor internalization.
      This role depends primarily upon two distinct, contiguous C-terminal beta
      arrestin motifs recognizing clathrin and the beta-adaptin subunit of AP2.
      However, a molecular basis is lacking to explain the different endocytic
      efficacies of the two beta-arrestin isoforms and the observation that beta
      arrestin N-terminal substitution mutants can act as dominant negative inhibitors
      of receptor endocytosis. Despite the near identity of the beta-arrestins
      throughout their N termini, sequence variability is present at a small number of
      residues and includes tyrosine to phenylalanine substitutions. Here we show that
      corresponding N-terminal (Y/F)VTL sequences in beta-arrestin1 and -2
      differentially regulate mu-adaptin binding. Our results indicate that the beta
      arrestin1 Tyr-54 lessens the interaction with mu-adaptin and moreover is a Src
      phosphorylation site. A gain of endocytic function is obtained with the beta
      arrestin1 Y54F substitution, which improves both the beta-arrestin1 interaction
      with mu-adaptin and the ability to enhance beta2-adrenergic receptor
      internalization. These data indicate that beta-arrestin2 utilizes mu-adaptin as
      an endocytic partner, and that the inability of beta-arrestin1 to sustain a
      similar degree of interaction with mu-adaptin may result from coordination of Tyr
      54 by neighboring residues or its modification by Src kinase. Additionally, these
      naturally occurring variations in beta-arrestins may also differentially regulate
      the composition of the signaling complexes organized on the receptor.

PMID- 17456467
TI  - A dominant negative form of the transcription factor c-Jun affects genes that
      have opposing effects on lipid homeostasis in mice.
AB  - c-Jun is a transcription factor activated by phosphorylation by the stress
      activated protein kinase/c-Jun N-terminal kinase pathway in response to
      extracellular signals and cytokines. We show that adenovirus-mediated gene
      transfer of the dominant negative form of c-Jun (dn-c-Jun) in C57BL/6 mice
      increased greatly apoE hepatic mRNA and plasma levels, increased plasma
      cholesterol, triglyceride, and very low density lipoprotein levels, and resulted
      in the accumulation of discoidal high density lipoprotein particles. A similar
      but more severe phenotype was generated by overexpression of the mouse apoE in
      C57BL/6 mice, suggesting that dyslipidemia induced by dn-c-Jun was the result of
      apoE overexpression. Unexpectedly, infection of apoE(-/-) mice with adenovirus
      expressing dn-c-Jun reduced plasma cholesterol by 70%, suggesting that dn-c-Jun
      affected other genes that control plasma cholesterol levels. To identify these
      genes, we performed whole genome expression analysis (34,000 genes) of isolated
      livers from two groups of five apoE(-/-) mice, infected with adenoviruses
      expressing either the dn-c-Jun or the green fluorescence protein. Bioinformatic
      analysis and Northern blotting validation revealed that dn-c-Jun increased 40
      fold the apoE mRNA and reduced by 70% the Scd-1 (stearoyl-CoA-desaturase 1) mRNA.
      The involvement of Scd-1 in lowering plasma cholesterol was confirmed by
      restoration of high cholesterol levels of apoE(-/-) mice following coinfection
      with adenoviruses expressing dn-c-Jun and Scd-1. In conclusion, dn-c-Jun appears
      to trigger two opposing events in mice that affect plasma cholesterol and
      triglyceride levels as follows: one results in apoE overexpression and triggers
      dyslipidemia and the other results in inhibition of Scd-1 and offsets
      dyslipidemia.

PMID- 17456470
TI  - Properties of RNA polymerase bypass mutants: implications for the role of ppGpp
      and its co-factor DksA in controlling transcription dependent on sigma54.
AB  - The bacterial nutritional and stress alarmone ppGpp and its co-factor DksA
      directly bind RNA polymerase to regulate its activity at certain sigma70
      dependent promoters. A number of promoters that are dependent on alternative
      sigma-factors function poorly in the absence of ppGpp. These include the
      Pseudomonas-derived sigma54-dependent Po promoter and several other sigma54
      promoters, the transcription from which is essentially abolished in Escherichia
      coli devoid of ppGpp and DksA. However, ppGpp and DksA have no apparent effect on
      reconstituted in vitro sigma54-transcription, which suggests an indirect
      mechanism of control. Here we report analysis of five hyper-suppressor mutants
      within the beta- and beta'-subunits of core RNA polymerase that allow high levels
      of transcription from the sigma54-Po promoter in the absence of ppGpp. Using in
      vitro transcription and competition assays, we present evidence that these core
      RNA polymerase mutants are defective in one or both of two properties that could
      combine to explain their hyper-suppressor phenotypes: (i) modulation of
      competitive association with sigma-factors to favor sigma54-holoenzyme formation
      over that with sigma70, and (ii) reduced innate stability of RNA polymerase
      promoter complexes, which mimics the essential effects of ppGpp and DksA for
      negative regulation of stringent sigma70-promoters. Both these properties of the
      mutant holoenzymes support a recently proposed mechanism for regulation of
      sigma54-transcription that depends on the potent negative effects of ppGpp and
      DksA on transcription from powerful stringent sigma70-promoters, and suggests
      that stringent regulation is a key mechanism by which the activity of alternative
      sigma-factors is controlled to meet cellular requirements.

PMID- 17456471
TI  - Atherogenic lipids induce adhesion of human coronary artery smooth muscle cells
      to macrophages by up-regulating chemokine CX3CL1 on smooth muscle cells in a
      TNFalpha-NFkappaB-dependent manner.
AB  - Recent genetic evidence has implicated the adhesive chemokine CX3CL1 and its
      leukocyte receptor CX3CR1 in atherosclerosis. We previously proposed a mechanism
      involving foam cell anchorage to vascular smooth muscle cells because: 1) CX3CL1
      and CX3CR1 are expressed by both cell types in mouse and human atherosclerotic
      lesions; 2) foam cells are reduced in lesions in cx3cr1(-/-)apoE(-/-) mice; and
      3) proatherogenic lipids (oxidized low density lipoprotein [oxLDL] and oxidized
      linoleic acid derivatives) induce adhesion of primary human macrophages to
      primary human coronary artery smooth muscle cells (CASMCs) in vitro in a
      macrophage CX3CR1-dependent manner. Here we analyze this concept further by
      testing whether atherogenic lipids regulate expression and function of CX3CL1 and
      CX3CR1 on CASMCs. We found that both oxLDL and oxidized linoleic acid derivatives
      indirectly up-regulated CASMC CX3CL1 at both the protein and mRNA levels through
      an autocrine feedback loop involving tumor necrosis factor alpha production and
      NF-kappaB signaling. Oxidized lipids also up-regulated CASMC CX3CR1 but through a
      different mechanism. Oxidized lipid stimulation also increased adhesion of
      macrophages to CASMCs when CASMCs were stimulated prior to assay, and a
      synergistic pro-adhesive effect was observed when both cell types were
      prestimulated. Selective inhibition with a CX3CL1-specific blocking antibody
      indicated that adhesion was strongly CASMC CX3CL1-dependent. These findings
      support the hypothesis that CX3CR1 and CX3CL1 mediate heterotypic anchorage of
      foam cells to CASMCs in the context of atherosclerosis and suggest that this
      chemokine/chemokine receptor pair may be considered as a pro-inflammatory target
      for therapeutic intervention in atherosclerotic cardiovascular disease.

PMID- 17456472
TI  - Replication fork reversal occurs spontaneously after digestion but is constrained
      in supercoiled domains.
AB  - Replication fork reversal was investigated in undigested and linearized
      replication intermediates of bacterial DNA plasmids containing a stalled fork.
      Two-dimensional agarose gel electrophoresis, a branch migration and extrusion
      assay, electron microscopy, and DNA-psoralen cross-linking were used to show that
      extensive replication fork reversal and extrusion of the nascent-nascent duplex
      occurs spontaneously after DNA nicking and restriction enzyme digestion but that
      fork retreat is severely limited in covalently closed supercoiled domains.

PMID- 17456473
TI  - The mast cell-restricted tryptase mMCP-6 has a critical immunoprotective role in
      bacterial infections.
AB  - Although it has been shown that mast cell-deficient mice have diminished innate
      immune responses against bacteria, the most important immunoprotective factors
      secreted from activated mast cells have not been identified. Mouse mast cell
      protease 6 is a tetramer-forming tryptase. This serine protease is abundant in
      the secretory granules and is exocytosed upon bacterial challenge. Here we have
      described the generation of a mast cell protease-6-null mouse. Our discovery that
      mice lacking this neutral protease cannot efficiently clear Klebsiella pneumoniae
      from their peritoneal cavities reveals an essential role for this serine
      protease, and presumably its human ortholog, in innate immunity.

PMID- 17456474
TI  - Osteopontin overexpression inhibits in vitro re-endothelialization via integrin
      engagement.
AB  - The extracellular matrix protein osteopontin (OPN) plays a nonredundant role in
      atherosclerosis and restenosis. Here we investigated the impact of OPN up
      regulation in an in vitro model of re-endothelialization after mechanical injury
      of the endothelial cell monolayer. Murine aortic endothelial (MAE) cells interact
      via alpha(v) integrins with the integrin-binding Arg-Gly-Asp OPN sequence and
      adhere to immobilized OPN. On this basis, MAE cells were stably transfected with
      a wild-type OPN cDNA (OPN-MAE cells), with an OPN mutant lacking the Arg-Gly-Asp
      sequence (DeltaRGD-OPN-MAE cells), or with vector alone (mock-MAE cells). When
      compared with mock-MAE and DeltaRGD-OPN-MAE cells, OPN-MAE cells showed a reduced
      sprouting activity in fibrin gel, a reduced motility in a Boyden chamber assay,
      and a reduced capacity to repair the wounded monolayer. Accordingly, OPN-MAE
      cells at the edge of the wound were unable to form membrane ruffles, to
      reorganize their cytoskeleton, and to activate the focal adhesion kinase and the
      small GTPase Rac1, key regulators of the cell entry into the first phase of the
      cell migration cycle. Accordingly, wounded OPN-MAE cells failed to activate the
      intracellular signals RhoA and ERK1/2, involved in the later phases of the cell
      migration cycle. Also, parental MAE cells showed reduced re-endothelialization
      after wounding when seeded on immobilized OPN and exhibited increased
      adhesiveness to OPN-enriched extracellular matrix. In conclusion, OPN up
      regulation impairs re-endothelialization by inhibiting the first phase of the
      cell migration cycle via alpha(v) integrin engagement by the extracellular matrix
      immobilized protein. This may contribute to the adverse effects exerted by OPN in
      restenosis and atherosclerosis.

PMID- 17456475
TI  - Validity of self-reported endoscopies of the large bowel and implications for
      estimates of colorectal cancer risk.
AB  - Large-bowel endoscopy with removal of polyps strongly reduces colorectal cancer
      risk. In epidemiologic studies, ascertainment of large-bowel endoscopies often
      relies on self-reports and might be prone to imperfect recall. In 2003-2004, the
      authors assessed the validity of self-reported colorectal endoscopies in a
      population-based case-control study including 540 cases and 614 controls from
      southwest Germany and calculated odds ratios of colorectal cancer risk according
      to self-reports and medical records. They sought to obtain all medical records
      for the last self-reported endoscopy and for a subsample of 100 subjects
      reporting no previous endoscopy. In total, 377 of 483 records could be obtained
      (78%). Sensitivity of self-reports was 100%, and specificity ranged from 93% to
      98% among subgroups defined by age, gender, education, family history of
      colorectal cancer, and case-control status. The odds ratios for colorectal cancer
      risk after previous colonoscopy were 0.31 (95% confidence interval: 0.21, 0.45)
      using self-reports and 0.31 (95% confidence interval: 0.20, 0.47) using medical
      records. However, agreement between self-reports and medical records was poor
      regarding type of endoscopy (colonoscopy, sigmoidoscopy, or rectoscopy; kappa =
      0.22), moderate concerning polypectomy (kappa = 0.58), and reasonable for year of
      examination (kappa = 0.70). Self-reports of previous colorectal endoscopies
      agreed well with medical records, but validation appears to be essential with
      respect to details of the examination.

PMID- 17456476
TI  - Secular trends in response rates for controls selected by random digit dialing in
      childhood cancer studies: a report from the Children's Oncology Group.
AB  - Since the mid-1990s, epidemiologists have anecdotally reported difficulty in
      recruiting controls using random digit dialing (RDD), but few empirical data have
      been published. From 1982 to 2003, epidemiologists from the Children's Oncology
      Group conducted 17 case-control studies using RDD controls. Data for calculating
      RDD and field response rates were available from eight and 13 of these studies,
      respectively. Over the period of analysis, the contact rate declined 2.5% per
      year (95% confidence interval (CI): -3.4, -1.6; p = 0.001), from above 90% in the
      1980s to 63-69% in the most recent studies. The response rate (the product of the
      contact and cooperation rates) showed a decline parallel to that of the contact
      rate (-2.4% per year, 95% CI: -3.2, -1.6; p < 0.001), from above 80% in the 1980s
      to 50-67% after the mid-1990s. Field response rates appeared to have declined
      modestly. The overall response rate (the product of the RDD response and field
      response rates) paralleled that of the RDD response rate and decreased 2.4% per
      year (95% CI: -2.7, -2.0; p < 0.001). The current low response rates for RDD
      indicate a substantial potential for selection bias and a need to seek
      alternative sources of controls.

PMID- 17456477
TI  - Dietary risk factors for kidney cancer in Eastern and Central Europe.
AB  - The authors examined the role of diet in the high-risk population of Central
      Europe among 1,065 incident kidney cancer cases and 1,509 controls in Russia,
      Romania, Poland, and the Czech Republic. They observed an increased association
      with kidney cancer for consumption of milk (odds ratio (OR) = 1.46, 95%
      confidence interval (CI): 1.15, 1.84) and yogurt (OR = 1.34, 95% CI: 1.07, 1.67),
      as well as all meat (OR = 1.27, 95% CI: 1.06, 1.51 compared with the lowest
      tertile). High consumption of all vegetables (OR = 0.64, 95% CI: 0.51, 0.80) and
      cruciferous vegetables (OR = 0.68, 95% CI: 0.55, 0.84) was inversely associated
      with kidney cancer. In addition, high consumption of preserved vegetables
      increased the risk of kidney cancer (OR = 1.66, 95% CI: 1.24, 2.21). Alcohol
      consumption did not appear to be associated with kidney cancer. This 1999-2003
      study provides further evidence that diet may play a role in the development of
      kidney cancer, with a particularly strong protective association for high
      vegetable intake. The increased risk associated with dairy products, preserved
      vegetables, and red meat provides clues to the high rates of kidney cancer in
      this population.

PMID- 17456478
TI  - Birth weight and systolic blood pressure in adolescence and adulthood: meta
      regression analysis of sex- and age-specific results from 20 Nordic studies.
AB  - The authors investigated the shape, sex- and age-dependency, and possible
      confounding of the association between birth weight and systolic blood pressure
      (SBP) in 197,954 adults from 20 Nordic cohorts (birth years 1910-1987), one of
      which included 166,249 Swedish male conscripts. Random-effects meta-regression
      analyses were performed on estimates obtained from age- and sex-stratified
      analyses within each of the cohorts. There was an inverse association between
      birth weight and SBP, irrespective of adjustment for concurrent body mass index.
      The association was linear for males, but for females with a birth weight greater
      than 4 kg, SBP increased with birth weight (p < 0.01). The association was
      stronger in the older age groups (p < 0.05), although this could have been a
      birth cohort effect. The association was stronger among females than among males
      (p = 0.005) when birth weight was less than or equal to 4 kg. The estimated
      effect of birth weight on SBP at age 50 years was -1.52 mmHg/kg (95% confidence
      interval: -2.27, -0.77) in men and -2.80 mmHg/kg (95% confidence interval: -3.85,
      -1.76) in women. Exclusion of the Swedish conscripts produced nearly identical
      results. This meta-analysis supports the evidence of an inverse birth weight-SBP
      association, regardless of adjustment for concurrent body size. It also reveals
      important heterogeneity in the shape and strength of the association by sex and
      age.

PMID- 17456479
TI  - Chromogranin A: friend or foe of the failing myocardium?

PMID- 17456480
TI  - Bleeding and blood transfusion issues in patients with non-ST-segment elevation
      acute coronary syndromes.
AB  - Antithrombotic therapy and invasive risk stratification in selected high-risk
      patients have improved outcomes from non-ST-segment elevation acute coronary
      syndromes (NSTE-ACS), but carry a risk of bleeding and blood transfusion.
      Although the true incidence of bleeding depends on the population studied (i.e.
      clinical trial vs. registry), the definition used, and the use of invasive
      procedures, it is becoming clear that bleeding is associated with an increased
      risk for adverse outcomes including myocardial infarction and death. Blood
      transfusion itself may carry a risk for ischaemic outcomes that is independent of
      bleeding. Therefore, therapies that provide an adequate level of anticoagulation
      to reduce ischaemia while simultaneously minimizing the risk of bleeding and
      transfusion have the potential to improve outcomes among patients with NSTE-ACS.
      Anticoagulants studied in recent clinical trials that have focused on bleeding
      reduction include fondaparinux and bivalirudin. In this review, we discuss the
      clinical trial evidence for these agents, the association between bleeding and
      clinical outcomes, the biology of blood transfusion and potential mechanisms
      underlying its association with adverse outcomes, and propose strategies to deal
      with bleeding complications. Future directions for research and clinical practice
      are also discussed.

PMID- 17456481
TI  - High-risk acute coronary syndrome patient and cardiac biomarkers in the emergency
      department: where do we stand?

PMID- 17456482
TI  - Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation
      myocardial infarction in elderly and younger patients: results from ExTRACT-TIMI
      25.
AB  - AIMS: To determine the effects of age on outcomes in patients with STEMI treated
      with a strategy of enoxaparin (ENOX) vs. unfractionated heparin (UFH). METHODS
      AND RESULTS: In the ExTRACT-TIMI 25 trial, 20,479 patients with STEMI were
      randomized in a double-blind fashion to UFH or ENOX. A novel reduced dose of ENOX
      was administered to patients >or=75 years, and a reduced dose in those with an
      estimated creatinine clearance of < 30 mL/min. Anti-Xa levels were measured in a
      subset of patients (n = 73). The exposure to anti-Xa over time was lower in the
      elderly (AUC(0-12 h) P < 0.0001; AUC(steady-state) P = 0.0046). The relative risk
      reduction (RR) with ENOX on the primary endpoint, i.e. death or non-fatal
      recurrent myocardial infarction, was greater in patients < 75 years (20%) than >
      75 years (6%), but the absolute benefits were similar. When compared with UFH,
      ENOX was associated with an RR of 1.67 for major bleeding, but the magnitude of
      the excess risk tended to be lower (RR = 1.15) in patients >or= 75 years assigned
      to ENOX. CONCLUSION: A dose reduction of ENOX in the elderly appears to be
      helpful in ameliorating bleeding risk. A strategy of ENOX was superior to UFH in
      both young and elderly patients with STEMI treated with fibrinolysis.

PMID- 17456483
TI  - Trimetazidine improves endothelial dysfunction in chronic heart failure: an
      antioxidant effect.
AB  - AIMS: To determine whether trimetazidine (TMZ) improves the endothelium-dependent
      relaxation (EDR) in chronic heart failure (CHF) and whether this effect is
      associated with its antioxidant properties. METHODS AND RESULTS: We studied 51
      patients (mean age 51.4 +/- 6 years) with CHF secondary to ischaemic
      cardiomyopathy (ejection fraction 32.5 +/- 4.5%). Plasma malondialdehyde (MDA)
      and lipid hydroperoxides (LOOHs) were measured from an antecubital vein on study
      entry and after a 4 week treatment with oral TMZ (20 mg tid) (group T, n = 23) or
      placebo (group C, n = 22) given randomly. Endothelium-dependent vasodilation of
      the radial artery (RA) was determined by intra-arterial infusion of acetylcholine
      (7.5, 15 and 30 microg/min). Patients receiving TMZ had an increased radial
      artery diameter (RAD) in response to each dose of acetylcholine infusion and a
      greater peak oxygen uptake (P < 0.01 vs. placebo). Plasma MDA and LOOHs levels
      were reduced at 4 weeks only in patients receiving TMZ (P < 0.001 for both vs.
      placebo). The improvement in ED-vasodilation was correlated with changes in peak
      VO(2) (r = 0.68; P = 0.0001), MDA (r = -0.61; P = 0.0002) and LOOHs (r = -0.59; P
      = 0.005). CONCLUSION: TMZ improves the ED-relaxation in patients with ischaemic
      cardiomyopathy. The antioxidant properties of TMZ may play a role.

PMID- 17456484
TI  - Recruitable collateral blood flow index predicts coronary instent restenosis
      after percutaneous coronary intervention.
AB  - AIMS: Collateral flow may influence long-term results after percutaneous coronary
      intervention (PCI) because of haemodynamic forces compete with the antegrade flow
      through the dilated lesion. The aim of the study was to assess the influence of
      recruitable collateral blood flow on restenosis in patients undergoing PCI with
      bare metal stents and using optimal antithrombotic treatment. METHODS AND
      RESULTS: In 95 patients, 95 de novo lesions were treated with PCI and a bare
      metal stent. Fractional flow reserve (FFR) at maximum hyperaemia induced by
      intravenous adenosine was determined. The pressure-derived collateral flow index
      (CFI) was determined as (P(w)-P(cvp))/(P(a)-P(cvp)), where P(w) represents
      coronary wedge pressure, P(cvp) central venous pressure, and P(a) mean aortic
      blood pressure. Both were measured during transient coronary occlusion by a
      balloon inflation of 30 s. Pre-interventional FFR (0.65 +/- 0.20) correlated
      inversely with the CFI (0.18 +/- 0.11), r =- 0.356, P < 0.001. After 9 months,
      binary angiographic restenosis (>/=50% diameter stenosis) was seen in 29.1%.
      Compared to patients with poorly developed collaterals (CFI < 0.25), patients
      with well-developed collaterals (CFI >/= 0.25) had a lower pre-interventional FFR
      (0.50 +/- 0.14 vs. 0.72 +/- 0.18, P < 0.001), a higher CFI (0.33 +/- 0.08 vs.
      0.13 +/- 0.07, P < 0.001), and a higher binary restenosis rate (54.2% vs. 19.4, P
      = 0.003). CFI*100 was an independent predictor of restenosis after 9 months (odds
      ratio 1.07, 95% CI 1.02-1.12, P = 0.016). CONCLUSION: Recruitable collateral
      blood flow measured during balloon inflation predicts angiographic instent
      restenosis in PCI patients treated with bare metal stents.

PMID- 17456485
TI  - Analysis of myocardial deformation based on ultrasonic pixel tracking to
      determine transmurality in chronic myocardial infarction.

PMID- 17456486
TI  - Feasibility study for the administration of remifentanil based on the difference
      between response entropy and state entropy.
AB  - BACKGROUND: Facial electromyography (FEMG) may have utility in the assessment of
      nociception during surgery. The difference between state entropy (SE) and
      response entropy (RE) is an indirect measure of FEMG. This study assesses an
      automated algorithm for remifentanil administration that is based on maintaining
      an entropy difference (ED) that is less than an upper boundary condition and
      greater than a lower boundary condition. METHODS: The algorithm was constructed
      with a development set (n = 40), and then automated and studied with a validation
      set (n = 20) of patients undergoing anterior cruciate ligament repair. The
      percentage of time that the ED was maintained between the two boundary conditions
      was determined. Remifentanil and propofol predicted effect-site concentrations
      (Ce) were determined at surgical milestones and, after drug discontinuation, the
      time to response to verbal stimulation and orientation was measured. RESULTS: The
      median (25th-75th percentile) per cent of time that the ED was recorded between
      the boundary conditions was 99.3% (98.1-99.8%). Predicted propofol (microg ml(
      1)) and remifentanil (ng ml(-1)) Ce (sd), respectively, were 3.5 and 4.0 at
      induction, 1.9 (0.8) and 7.2 (3.7) at the end of surgery, and 1.1 (0.5) and 3.2
      (2.2) at eye opening. The median time to eye opening and orientation was 3.8 and
      6.8 min, respectively. CONCLUSION: This feasibility study supports the concept
      that remifentanil may be delivered using an algorithm that maintains the
      difference between SE and RE between the upper and lower boundary condition.

PMID- 17456487
TI  - Urotensin II: from osmoregulation in fish to cardiovascular regulation in man.

PMID- 17456488
TI  - Coronary artery stents and non-cardiac surgery.
AB  - The utility of interventional cardiology has developed significantly over the
      last two decades with the introduction of coronary angioplasty and stenting, with
      the associated antiplatelet medications. Acute coronary stent occlusion carries a
      high morbidity and mortality, and the adoption of therapeutic strategies for
      prophylaxis against stent thrombosis has major implications for surgeons and
      anaesthetists involved in the management of these patients in the perioperative
      period. Currently, there is limited published information to guide the clinician
      in the optimal care of patients who have had coronary stents inserted when they
      present for non-cardiac surgery. This review examines the available literature on
      the perioperative management of these patients. A number of key issues are
      identified: the role of surgery vs percutaneous coronary intervention for
      coronary revascularization in the preoperative period; the different types of
      coronary stents currently available; the emerging issues related to drug-eluting
      stents; the pathophysiology of coronary stent occlusion; and the recommended
      antiplatelet regimes that the patient with a coronary stent will be receiving.
      The role of preoperative platelet function testing is also discussed, and the
      various available tests are listed. Appropriate management by all the clinicians
      involved with patients with coronary stents undergoing a variety of non-cardiac
      surgical procedures is essential to avoid a high incidence of postoperative
      cardiac mortality and morbidity. The review examines the evidence available for
      the perioperative strategies aimed at reducing adverse outcomes in a number of
      different clinical scenarios.

PMID- 17456489
TI  - Validation of pulse contour derived stroke volume variation during modifications
      of cardiac afterload.
AB  - BACKGROUND: Left ventricular stroke volume variation (SVV) or its surrogates are
      useful tools to assess fluid responsiveness in mechanically ventilated patients.
      So far it is unknown, how changes in cardiac afterload affect SVV. Therefore,
      this study compared left ventricular SVV derived by pulse contour analysis with
      SVV measured using an ultrasonic flow probe and investigated the influence of
      cardiac afterload on left ventricular SVV. METHODS: In 13 anaesthetized,
      mechanically ventilated pigs [31(SD 6) kg], we compared cardiac output (CO),
      stroke volume (SV), and SVV determined by pulse contour analysis and by an
      ultrasonic aortic flow signal (Bland-Altman analysis). After obtaining baseline
      measurements, cardiac afterload was increased using phenylephrine and decreased
      using adenosine (both continuously administered). Measurements were performed
      with a constant tidal volume (12 ml kg-1) without PEEP. RESULTS: Neither
      increasing mean arterial pressure (MAP) [from 59 (7) to 116 (19)] nor decreasing
      MAP [from 63 (7) to 39 (4)] affected CO, SV, and SVV (both methods). Method
      comparison revealed a bias for SVV of 0.1% [standard error of the mean (SE) 0.8]
      at baseline, -1.2% (SE 0.8) during decreased and 4.0% (SE 0.7) during increased
      afterload, the latter being significantly different from the others (P<0.05).
      Thereby, pulse contour analysis tended to underestimate SVV during decreased
      afterload and to overestimate SVV during increased afterload. Limits of agreement
      were approximately 6% for all points of measurement. CONCLUSIONS: Left
      ventricular SVV is not affected by changes in cardiac afterload. There is a good
      agreement of pulse contour with flow derived SVV. The agreement decreases, if
      afterload is extensively augmented.

PMID- 17456490
TI  - Intra-abdominal pressure measurement: validation of intragastric pressure as a
      measure of intra-abdominal pressure.
AB  - BACKGROUND: The diagnosis of abdominal compartment syndrome depends upon the
      demonstration of an elevated intra-abdominal pressure (IAP). Direct measures of
      IAP are impractical in the critical care unit; intravesical pressure (IVP) and
      intragastric pressure (IGP) should represent acceptable surrogate measures. IVP
      is the preferred measure of IAP in critical care. We considered that IGP
      represents a practical alternative. The objective of this preliminary study was
      to observe the relationship between IGP and IAP. METHODS: After Institutional
      Ethics Board approval, 29 patients having elective laparoscopic surgery were
      recruited. IAP was measured directly via the abdominal trochar. This was compared
      with IGP measured via a commercial balloon catheter placed into the stomach.
      RESULTS: Measured IGP was always more positive than IAP; both showed linear
      correlation (r2>0.9). When IGP was calibrated against IAP, an estimated
      difference between the IGP and IAP of+/-2.5 mm Hg for 95% of the measurements was
      seen. CONCLUSIONS: The study demonstrates the strength of the relationship
      between IGP and IAP in normal individuals. Application of IGP measurement in the
      critical care patient is necessary to demonstrate its suitability for continuous
      IAP assessment.

PMID- 17456491
TI  - HES 130/0.42 shows less alteration of pharmacokinetics than HES 200/0.5 when
      dosed repeatedly.
AB  - BACKGROUND: Hydroxyethyl starches (HES) accumulate in the circulation when
      administered repeatedly. Accumulation is thought to be partly responsible for
      undesirable effects (tissue storage, blood coagulation impairment, and itching).
      HES 130/0.42 with low molecular weight and a low level of substitution has
      recently been developed in order to reduce those risks. METHODS: In healthy
      volunteers, the pharmacokinetics of HES 130/0.42/6:1 were investigated using a
      crossover design with HES 200/0.5 serving as control. Fifty grams of either HES
      were administered in 4 h day-1 for a period of five consecutive days. HES serum
      concentrations were used for computation of pharmacokinetic coefficients. Change
      between the first and fifth infusion in the area under the concentration curve
      (AUC) served as the primary measurement. RESULTS: Although the circulation was
      freed from the load with HES 130/0.42 within 20 h after end of the previous
      infusion, the amount of HES 200/0.5 increased continuously from one
      administration to the other. AUC and elimination half-life (t1/2) were
      significantly lower with HES 130/0.42. AUC and t1/2 of HES 200/0.5 showed an
      increase between the first and the fifth administration whereas only a minimal
      shift was present with HES 130/0.42. Haemodilution via HES 200/0.5 did not change
      over time. CONCLUSIONS: Repeated administration of HES 130/0.42 shows no
      accumulation and fewer tendencies to time-dependent changes in pharmacokinetic
      parameters than HES 200/0.5. The improved reproducibility may improve drug
      safety, particularly as the accumulation of residual starch with HES 200/0.5 does
      not contribute to the colloid's volume effect, but may rather increase the risk
      of undesired reactions.

PMID- 17456492
TI  - Predicting response to recombinant factor VIIa in non-haemophiliac patients with
      severe haemorrhage.

PMID- 17456493
TI  - Sevoflurane and analgesia.

PMID- 17456494
TI  - Alzheimer's disease and anaesthesia.

PMID- 17456495
TI  - Coma after combined spinal-epidural anaesthesia.

PMID- 17456496
TI  - Bedside prediction of central venous catheter insertion depth.

PMID- 17456497
TI  - Entrapped central venous catheter.

PMID- 17456498
TI  - Postoperative management of patients with obstructive sleep apnoea syndrome.

PMID- 17456499
TI  - Structural modelling and mutation analysis of a nociceptin receptor and its
      ligand complexes.
AB  - We recently modelled and proposed four ligand-bound conformations for a G-protein
      coupled receptor, namely, forms I, II, III and IV, based on the 3D structure and
      functional evidences for rhodopsin. In this study, the same strategy was applied
      to a human nociceptin receptor (NR), in order to predict ligand-bound receptor
      structures. Additionally, site-directed mutagenesis studies were carried out to
      evaluate these structures. A Thr138Ala mutant demonstrated the same affinity for
      [Phe(1)Psi(CH(2)-NH)Gly(2)]nociceptin(1-13)NH(2) as the wild-type receptor;
      however, the affinity of this mutant for nociceptin was 20-fold lower than that
      of the wild type. A Ser223Ala mutation showed the same characteristics as those
      of the wild type. On the other hand, a Gln280Ala mutation reduced the affinity to
      nociceptin by more than 60-folds. These results suggested that a change in the
      conformation of NR following agonist binding did not accompany the rigid-body
      rotation of the sixth transmembrane segment that was reported for an adrenergic
      receptor and a kappa-opioid receptor. NR is potently activated not only by
      nociceptin but also a synthetic peptide, i.e. Ac-RYYRIK-NH(2), although the amino
      acid sequences of both these ligands are completely different. The model explains
      why both the ligands activate NR and shows that their receptor-bound
      conformations have similar 3D structures.

PMID- 17456500
TI  - Marked difference between self-aggregations of first and fourth repeat peptides
      on tau microtubule-binding domain in acidic solution.
AB  - The heparin-induced self-aggregation behaviours of four repeat peptides (R1-R4)
      in an acidic solution (pH = 4.5) were investigated by fluorescence and circular
      dichroism (CD) measurements and compared with those in a neutral solution (pH =
      7.5). In contrast with the self-aggregation-resistive behaviours of the R1 and R4
      repeat peptides in the neutral solution, the R4 peptide formed a filament
      similarly to the R2 and R3 peptides in the acidic solution, whereas the R1
      peptide still showed resistive behaviour for filament formation. This is the
      first report on the markedly different self-aggregation behaviours of the first
      and fourth repeat peptides on tau microtubule-binding domain.

PMID- 17456501
TI  - Studying on the 19-bp palindrome repeats in human cytomegalovirus immediate early
      enhancer/promoter reveals their diversity in function for the promoter activity.
AB  - The human cytomegalovirus major immediate early enhancer/promoter (HCMV MIEP),
      extending from -588 to +1 relative to the transcription start site, contains a
      series of reiterated cis-acting elements, such as 19-bp repeats, which occur four
      times in the enhancer/promoter region. However, it is still not clear whether
      these elements repeat just for backing up or they really execute various
      indispensable functions. We show here that these reiterated elements are
      functionally different from each other through serial deletion mutation and site
      directed mutation. In addition, we also found that the CG-reverse in the first 19
      bp repeat could improve the transcription activity of MIEP in HeLa cells and
      impair the protein-binding capacity in the EMSA assay. The expression feature of
      this mutated MIEP in transgenic mice further confirmed its stronger and more
      universal transcription activity in vivo.

PMID- 17456502
TI  - Changes in physician supply and scope of practice during a malpractice crisis:
      evidence from Pennsylvania.
AB  - The extent to which liability costs cause physicians to restrict their scope of
      practice or cease practicing is controversial in policy debates over malpractice
      "crises." We used insurance department administrative data to analyze specialist
      physician scope-of-practice changes and exits in Pennsylvania in 1993-2002. In
      most specialties the proportions of high-risk specialists restricting their scope
      of practice did not increase during the crisis; however, the supply of
      obstetrician-gynecologists decreased by 8 percent in the three years following
      premium increases in 1999. We discuss methodological issues that could explain
      the disparate findings regarding physician supply effects in studies using
      administrative data sets and survey data.

PMID- 17456503
TI  - Risk factors for accident and emergency (A&E) attendance for asthma in inner city
      children.
AB  - BACKGROUND: Inner city children make heavy use of accident and emergency (A&E)
      services for asthma. Developing strategies to reduce this requires a better
      understanding of the risk factors. METHODS: A case-control study was carried out
      of children with asthma living in south-east London: 1018 children who attended
      A&E for asthma over 1 year and 394 children who had not attended A&E for asthma
      over the previous year. The main risk factors were socioeconomic status, home
      environment, routine asthma management and parents' psychological responses to
      and beliefs about the treatment of asthma attacks. RESULTS: A&E attendance was
      more common in children living in poorer households. No associations were found
      with home environment or with measures of routine asthma care. Children who had
      attended outpatients were much more likely to attend A&E (odds ratio (OR) 13.17,
      95% CI 7.13 to 24.33). Other risk factors included having a parent who reported
      feeling alone (OR 2.58, 95% CI 1.71 to 3.87) or panic or fear (OR 2.62. 95% CI
      1.75 to 3.93) when the child's asthma was worse; and parental belief that the
      child would be seen more quickly in A&E than at the GP surgery (OR 2.48, 95% CI
      1.62 to 3.79). Parental confidence in the GP's ability to treat asthma attacks
      reduced the risk of attending A&E (OR 0.30, 95% CI 0.17 to 0.54). CONCLUSIONS:
      There is no evidence that passive smoking, damp homes or poor routine asthma care
      explains heavy inner city use of A&E in children with asthma. Reducing A&E use is
      unlikely to be achieved by improving these, but identifying appropriate settings
      for treating children with asthma attacks and communicating these effectively may
      do so.

PMID- 17456504
TI  - Isolation and characterization of a Vitis vinifera transcription factor, VvWRKY1,
      and its effect on responses to fungal pathogens in transgenic tobacco plants.
AB  - Pathogen attack represents a major problem for viticulture and for agriculture in
      general. At present, the use of phytochemicals is more and more restrictive, and
      therefore it is becoming essential to control disease by having a thorough
      knowledge of resistance mechanisms. The present work focused on the trans
      regulatory proteins potentially involved in the control of the plant defence
      response, the WRKY proteins. A full-length cDNA, designated VvWRKY1, was isolated
      from a grape berry library (Vitis vinifera L. cv. Cabernet Sauvignon). It encodes
      a polypeptide of 151 amino acids whose structure is characteristic of group IIc
      WRKY proteins. VvWRKY1 gene expression in grape is regulated in a developmental
      manner in berries and leaves and by various signal molecules involved in defence
      such as salicylic acid, ethylene, and hydrogen peroxide. Biochemical analysis
      indicates that VvWRKY1 specifically interacts with the W-box in various
      nucleotidic contexts. Functional analysis of VvWRKY1 was performed by
      overexpression in tobacco, and transgenic plants exhibited reduced susceptibility
      to various fungi but not to viruses. These results are consistent with a possible
      role for VvWRKY1 in grapevine defence against fungal pathogens.

PMID- 17456505
TI  - Cloning, gene mapping, and functional analysis of a fructan 1-exohydrolase (1
      FEH) from Lolium perenne implicated in fructan synthesis rather than in fructan
      mobilization.
AB  - Fructans, which are beta-(2,1) and/or beta-(2,6) linked polymers of fructose, are
      important storage carbohydrates in many plants. They are mobilized via fructan
      exohydrolases (FEHs). The cloning, mapping, and functional analysis of the first
      1-FEH (EC 3.2.1.153) from Lolium perenne L. var. Bravo is described here. By
      screening a perennial ryegrass cDNA library, a 1-FEH cDNA named Lp1-FEHa was
      cloned. The Lp1-FEHa deduced protein has a low iso-electric point (5.22) and it
      groups together with plant FEHs and cell-wall type invertases. The deduced amino
      acid sequence shows 75% identity to wheat 1-FEH w2. The Lp1-FEHa gene was mapped
      at a distal position on the linkage group 3 (LG3). Functional characterization of
      the recombinant protein in Pichia pastoris demonstrated that it had high FEH
      activity towards 1-kestotriose, 1,1-kestotetraose, and inulin, but low activity
      against 6-kestotriose and levan. Like other fructan-plant FEHs, no hydrolase
      activity could be detected towards sucrose, convincingly demonstrating that the
      enzyme is not a classic invertase. The expression pattern analysis of Lp1-FEHa
      revealed transcript accumulation in leaf tissues accumulating fructans while
      transcript level was low in the photosynthetic tissues. The high expression level
      of this 1-FEH in conditions of active fructan synthesis, together with its low
      expression level when fructan contents are low, suggest that it might play a role
      as a beta-(2,1) trimming enzyme acting during fructan synthesis in concert with
      fructan synthesis enzymes.

PMID- 17456506
TI  - A controlled clinical trial of the effects of the Twin Block and Dynamax
      appliances on the hard and soft tissues.
AB  - The aim of this controlled trial was to identify and quantify skeletal, soft
      tissue and dental changes during treatment, and immediately post-treatment with
      Twin Block (TB) or Dynamax appliance using the techniques of three-dimensional
      (3D)optical surface laser scanning, cephalometric, and clinical measurements.
      Sixty-two Caucasian subjects, 36 males aged 11-14 years and 26 females aged 10-13
      years were enrolled in the study. The patients were placed in two groups, matched
      for gender and age and subsequently allocated randomly for treatment with either
      a TB or Dynamax appliance. Active treatment lasted 9 months followed by 3 months'
      post-treatment observation. Laser scanning and clinical measurements were taken
      at 3-monthly intervals and final cephalometric records after 12 months.
      Statistical analysis was performed using Wilcoxon's matched-pairs signed-rank
      tests. The non-compliance rates were the same for both groups (9 per cent), but a
      greater incidence of breakages was found in the Dynamax group. The TB was found
      to produce slightly more antero-posterior skeletal change, median ANB reduction,
      TB=2 degrees, Dynamax 1.1 degree (P=0.006), and similar forward movements of the
      chin and was associated with larger increases in the vertical facial dimension,
      median total anterior face height increase; TB=3.2 mm, Dynamax = 2.8 mm (P=0.03).
      The soft tissue vertical cephalometric increases were 3.6 mm with the TB, 2.0 mm
      with the Dynamax (P=0.036), and with laser scanning 5.05 and 2.6 mm,
      respectively, a difference which is likely to be more clinically relevant. The
      median post-treatment changes in soft tissue pogonion were -0.65 mm in the TB and
      +0.22 mm in the Dynamax group. The optical surface scanning mark and measure
      system is a valid method for quantifying soft tissue changes.

PMID- 17456507
TI  - Parents of deaf children seeking hearing loss-related information on the
      internet: the Australian experience.
AB  - Parents whose children are diagnosed in an infant screening program are required
      to make some difficult choices about the management of the hearing loss at a time
      when they are emotionally vulnerable. They are required to evaluate information
      and outcomes regarding issues such as technology for hearing impairment,
      communication options, education, and rehabilitation. The World Wide Web has
      become an important resource of health information for both health consumers and
      practitioners. The ability to obtain accurate health information online quickly,
      conveniently, and privately provides opportunity to make informed decisions.
      However, little is known about the level of the use of the Internet to acquire
      health information, particularly in the case of parents of deaf children seeking
      information. This study confirms that searches for health information on the
      Internet are conducted primarily by mothers. In the Australian context, there is
      minimal online information available to families beyond early intervention.
      Information on education issues, mental health, and deafness or the day-to-day
      management of a child or adolescent with a hearing loss are neglected topics on
      Web sites. This study also revealed that the majority of respondents had never
      visited HealthInsite or Medline Plus, two gateway sites for reliable consumer
      health information, although the information on these sites is more generic in
      nature and unlikely to assist parents to make informed choices on complex issues
      such as communication options or education. However, the study suggested that
      half the parents have talked to their doctor or hearing professional about
      information they found on the Internet, which is an encouraging tendency.

PMID- 17456508
TI  - Cytotoxicity in cultured mammalian cells is a function of the method used to
      estimate it.
AB  - Up to prescribed limits, the maximum test compound concentrations used in
      mammalian cell genotoxicity assays in vitro are determined by cytotoxicity,
      unless limited by solubility in solvents or culture medium. However,
      'cytotoxicity' is different in the various test systems, both in the methods used
      to estimate it and the levels of toxicity that must be achieved. For example, in
      cytogenetic assays, the acceptable level of toxicity is defined as a 'significant
      reduction (>50%)' in cell number, culture confluency or mitotic index (MI) (OECD
      473, ICH S2A), whereas mutation tests require relative total growth or cloning
      efficiency (CE) to be reduced by 80-90% (OECD 476, ICH S2A). In this study using
      mouse lymphoma cells, it was shown that, for a variety of agents with differing
      modes of action, cytotoxicity varies considerably depending on the method used to
      estimate it. Specifically, trypan blue exclusion, MI and binucleate incidence all
      grossly underestimate cytotoxicity in comparison with cell growth or CE. If the
      performance of different test systems is to be compared, or if data from
      different assays are to be used for the meaningful assessment of a novel chemical
      entity, it is essential that similar methods to determine cytotoxicity are used
      for them all. The purpose of this paper is not to recommend a specific method to
      determine cytotoxicity, although it can be argued that any such method must
      quantify the proportion of cells capable of division following treatment, but
      rather to draw attention to the fact that apparent toxicity depends upon the
      method used to estimate it.

PMID- 17456509
TI  - New serological markers in inflammatory bowel disease are associated with
      complicated disease behaviour.
AB  - BACKGROUND AND AIMS: Several antibodies have been associated with Crohn's disease
      and are associated with distinct clinical phenotypes. The aim of this study was
      to determine whether a panel of new antibodies against bacterial peptides and
      glycans could help in differentiating inflammatory bowel disease (IBD), and
      whether they were associated with particular clinical manifestations. METHODS:
      Antibodies against a mannan epitope of Saccharomyces cerevisiae (gASCA),
      laminaribioside (ALCA), chitobioside (ACCA), mannobioside (AMCA), outer membrane
      porins (Omp) and the atypical perinuclear antineutrophilic cytoplasmic antibody
      (pANCA) were tested in serum samples of 1225 IBD patients, 200 healthy controls
      and 113 patients with non-IBD gastrointestinal inflammation. Antibody responses
      were correlated with the type of disease and clinical characteristics. RESULTS:
      76% of Crohn's disease patients had at least one of the tested antibodies. For
      differentiation between Crohn's disease and ulcerative colitis, the combination
      of gASCA and pANCA was most accurate. For differentiation between IBD, healthy
      controls and non-IBD gastrointestinal inflammation, the combination of gASCA,
      pANCA and ALCA had the best accuracy. Increasing amounts and levels of antibody
      responses against gASCA, ALCA, ACCA, AMCA and Omp were associated with more
      complicated disease behaviour (44.7% versus 53.6% versus 71.1% versus 82.0%, p <
      0.001), and a higher frequency of Crohn's disease-related abdominal surgery
      (38.5% versus 48.8% versus 60.7% versus 75.4%, p < 0.001). CONCLUSIONS: Using
      this new panel of serological markers, the number and magnitude of immune
      responses to different microbial antigens were shown to be associated with the
      severity of the disease. With regard to the predictive role of serological
      markers, further prospective longitudinal studies are necessary.

PMID- 17456510
TI  - Reduced mucosal antimicrobial activity in Crohn's disease of the colon.
AB  - OBJECTIVES: In order to maintain the mucosal barrier against luminal
      microorganisms the intestinal epithelial cells synthesise various broad-spectrum
      antimicrobial peptides including defensins and cathelicidins. Recent studies
      indicate that both may be deficient in Crohn's disease. To elucidate the possible
      functional consequences of this deficiency antimicrobial activity in colonic
      mucosa from patients with inflammatory bowel disease and healthy controls was
      investigated. METHODS: A flow cytometric assay was established to quantitate
      bacterial killing and test the antibacterial activity of cationic peptide
      extracts from colonic biopsies taken from patients with active or inactive
      ileocolonic or colonic Crohn's disease (n = 22), ulcerative colitis (n = 29) and
      controls (n = 13) against clinical isolates of Bacteroides vulgatus and
      Enterococcus faecalis or the reference strains Escherichia coli American Type
      Culture Collection (ATCC) 25922 and Staphylococcus aureus ATCC 25923. RESULTS:
      Compared with controls and ulcerative colitis there was a reduced antimicrobial
      effect in Crohn's disease extracts that was most evident against B. vulgatus. The
      antimicrobial effect against E. coli and E. faecalis was significantly lower in
      Crohn's disease compared with ulcerative colitis. Activity against S. aureus
      disclosed a similar pattern, but was less pronounced. The differences were
      independent of the inflammation status or concurrent steroid treatment. Bacteria
      incubated with biopsy extracts from ulcerative colitis patients frequently showed
      a characteristic change in cell size and granularity, compatible with more
      extensive membrane disintegration, compared with bacteria incubated with extracts
      from controls or Crohn's disease. CONCLUSION: Crohn's disease of the colon is
      characterized by a diminished functional antimicrobial activity that is
      consistent with the reported low antibacterial peptide expression.

PMID- 17456511
TI  - Simultaneously optimizing dose and schedule of a new cytotoxic agent.
AB  - BACKGROUND: Traditionally, phase I clinical trial designs are based upon one
      predefined course of treatment while varying among patients the dose given at
      each administration. In actual medical practice, patients receive a schedule
      comprised of several courses of treatment, and some patients may receive one or
      more dose reductions or delays during treatment. Consequently, the overall risk
      of toxicity for each patient is a function of both actual schedule of treatment
      and the differing doses used at each adminstration. PURPOSE: Our goal is to
      provide a practical phase I clinical trial design that more accurately reflects
      actual medical practice by accounting for both dose per administration and
      schedule. METHODS: We propose an outcome-adaptive Bayesian design that
      simultaneously optimizes both dose and schedule in terms of the overall risk of
      toxicity, based on time-to-toxicity outcomes. We use computer simulation as a
      tool to calibrate design parameters. RESULTS: We describe a phase I trial in
      allogeneic bone marrow transplantation that was designed and is currently being
      conducted using our new method. Our computer simulations demonstrate that our
      method outperforms any method that searches for an optimal dose but does not
      allow schedule to vary, both in terms of the probability of identifying optimal
      (dose, schedule) combinations, and the numbers of patients assigned to those
      combinations in the trial. LIMITATIONS: Our design requires greater sample sizes
      than those seen in traditional phase I studies due to the larger number of
      treatment combinations examined. Our design also assumes that the effects of
      multiple administrations are independent of each other and that the hazard of
      toxicity is the same for all administrations. CONCLUSIONS: Our design is the
      first for phase I clinical trials that is sufficiently flexible and practical to
      truly reflect clinical practice by varying both dose and the timing and number of
      administrations given to each patient.

PMID- 17456512
TI  - Eliciting and using expert opinions about dropout bias in randomized controlled
      trials.
AB  - BACKGROUND: The analysis of clinical trials with dropout usually assumes the
      missing data are ;missing at random', i.e. given an individual's past observed
      data, their probability of dropout does not depend on their present outcome.
      However, in many settings this assumption is implausible, so it is sensible to
      assess the robustness of conclusions to departures from missing at random.
      PURPOSE: To develop a practical, accessible, approach that allows expert opinions
      about the degree of departure from missing at random in the analysis of a
      clinical trial to be meaningfully and accurately elicited and incorporated in
      sensitivity analysis. METHODS: We elicit experts' prior beliefs about the mean
      difference between missing and observed outcomes in each trial arm. Then we
      perform a Bayesian synthesis of the information in the trial data with that in
      the experts' prior, using (i) a full Bayesian analysis for which we give WinBUGS
      code, and (ii) a simple approximate formula for the estimated treatment effect
      and its standard error. We illustrate our approach by re-analysing a recent trial
      of interventions to improve the quality of peer review. RESULTS: In the peer
      review trial, the approximate formula agreed well with the full Bayesian
      analysis, and both showed substantially larger standard errors than an analysis
      assuming missing at random. LIMITATIONS: Strictly, the method is only applicable
      if the outcome is normally distributed. We did not elicit the full bivariate
      prior distribution, and instead used a sensitivity analysis. Our approach is not
      designed to incorporate prior beliefs about the intervention effect itself.
      CONCLUSIONS: Our proposed approach allows for the greater uncertainty introduced
      by missing data that are potentially informatively missing. It can therefore
      claim to be a truly conservative method, unlike methods such as ;last observation
      carried forward'. It is practical and accessible to non-statisticians. It should
      be considered as part of the design and analysis of future clinical trials.

PMID- 17456513
TI  - A decision rule for sequential monitoring of clinical trials with a primary and
      supportive outcome.
AB  - BACKGROUND: Many clinical trials have multiple outcomes. Formal interim
      monitoring guidelines that take account of multiple outcomes can be useful to
      Data Monitoring Committees (DMC). Previous research has focused on marginal
      criteria that control the overall type I error for bivariate endpoints
      corresponding to efficacy and safety. Usually, an 'or' decision rule is used,
      that is, the trial is stopped when either the safety or the efficacy endpoint
      crosses a boundary. PURPOSE: In many trials there is not a clear difference
      between what is considered a safety and an efficacy endpoint. Likewise, in some
      studies there is interest in more than one disease outcome and while there may be
      a primary efficacy endpoint, interim monitoring might also involve a measure of
      overall health. For these situations, an ;and' decision rule might be more
      appropriate; that is, the trial is stopped only when both endpoints cross a
      boundary. Formulation of this new decision rule at the design stage would
      encourage more discussion among trial investigators of monitoring guidelines and
      would result in improved guidelines for DMCs. METHODS: In this paper, we propose
      stopping guidelines for such trials with two major outcomes that control the
      overall type I error and stop early only if both endpoints indicate superiority
      for the same treatment. Trials with two treatments are considered and we develop
      sets of paired two-sided boundaries, permitting one endpoint to be primary and
      the other supportive, with or without pre-specifying which one is primary.
      RESULTS: The results show that the boundaries depend on the correlation between
      the two outcomes. The critical values increase as the correlation increases in
      most cases. For low to moderate correlation and before the last stage, critical
      values based on the O'Brien Fleming (or Pocock) error spending function that
      consider the correlation are lower than those which do not. LIMITATIONS:
      Investigators might not want to stop a trial early with the small size of the
      critical values that result from this decision rule for some situations. For a
      trial in which the treatment effect for one outcome is large, while for the other
      it is small, the proposed decision rule has low power to accept this treatment
      for its superiority on both outcomes. Also, we do not provide a separate P-value
      for each outcome since type I error is not controlled for individual null
      hypotheses. CONCLUSIONS: For trials involving two major health outcomes these
      stopping guidelines may be appropriate for DMCs when the trial investigators and
      sponsor recommend that early termination not be considered unless the findings
      are consistent for both outcomes.

PMID- 17456514
TI  - Cost-effectiveness in clinical trials: using multiple imputation to deal with
      incomplete cost data.
AB  - BACKGROUND: Cost-effectiveness has become an important outcome in many clinical
      trials and has resulted in the collection of resource use data and the
      calculation of costs for individual patients. A specific example is a Cancer
      Research UK phase III trial comparing chemotherapy (CT) against standard
      palliative care in patients with advanced non-small cell lung cancer. Resource
      usage from trial entry until death were collected and costs obtained on a subset
      of 115 trial patients. For some patients, however, the unavailability of medical
      notes resulted in some cost components, and hence total cost, being missing. The
      82 patients with complete data were not representative of all trial patients in
      terms of effectiveness and thus it was necessary to address the missing data
      problem. METHODS: Multiple imputation (MI) was used to impute values for the
      unobserved individual cost components, allowing total cost to be calculated and
      cost-effectiveness carried out for all patients in the cost sub-study. The
      results are compared with those from a complete case analysis. RESULTS: After MI,
      the results indicated that CT had a high probability of being cost-effective for
      a societal willingness to pay over 20,000 Pounds per life-year gained. This was
      in stark contrast with the complete case analysis, which suggested that CT was
      not a cost-effective use of resources at any reasonable level of willingness to
      pay for a life-year. LIMITATIONS: Our findings are based on a relatively small
      retrospective study with all events observed. CONCLUSION: In conclusion, cost
      effectiveness analysis of the complete cases only may give biased results, and
      therefore, in situations where there are missing costs, MI is recommended.

PMID- 17456516
TI  - Target practice: oncology drug development in the era of genomic medicine.

PMID- 17456518
TI  - Developing targeted therapy.

PMID- 17456517
TI  - New challenges for 21st century clinical trials.

PMID- 17456521
TI  - Integrating smoking cessation into mental health care for post-traumatic stress
      disorder.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) is associated with a high
      prevalence of smoking, heavy cigarette consumption and low cessation rates.
      PURPOSE: This manuscript describes the design of a randomized, multisite
      effectiveness trial to test whether integrating smoking cessation treatment into
      mental health care (integrated care) improves prolonged abstinence rates among
      veterans with PTSD, compared with referral to specialized smoking cessation
      clinics (usual standard of care). Secondary objectives are to assess the cost
      effectiveness of integrated care relative to usual standard of care, identify
      treatment variables that mediate differences between conditions in outcome and
      determine whether smoking cessation is associated with worsening PTSD and/or
      depression. METHODS: Following randomization, subjects (projected n = 1400) from
      10 Veterans Health Administration (VHA) medical centers complete follow-up
      assessments every three or six months for up to four years. Endpoints include 1
      year prolonged abstinence at 18 months postrandomization, 7- and 30-day point
      prevalence abstinence and measures of depression, PTSD and economic outcomes.
      RESULTS: This study is unique in providing the largest scale test of the
      feasibility and effectiveness of having mental health clinicians implement
      evidence-based smoking cessation treatment in psychiatric care settings for
      veterans with PTSD. It incorporates methodological features that are desirable
      for cessation treatment trials, including: a) assessment of clinically meaningful
      long-term smoking outcomes; b) a manual guiding delivery of the experimental
      intervention; c) independent ratings of clinician competence and treatment
      adherence and d) methods for training clinicians that would enhance
      implementation of tobacco cessation treatment in large health care systems.
      LIMITATIONS: Use of an exclusively VHA sample with few females limits
      generalizability. CONCLUSIONS: The process for meeting challenges in designing
      this study may provide planning of other large-scale clinical effectiveness
      trials in tobacco control. Findings have potential to initiate system-wide change
      in clinical practice patterns for tobacco cessation treatment involving patients
      with mental disorders.

PMID- 17456522
TI  - Statistical design of THRio: a phased implementation clinic-randomized study of a
      tuberculosis preventive therapy intervention.
AB  - BACKGROUND: Tuberculosis (TB) is a major public health problem in Rio de Janeiro,
      where a high proportion of HIV-infected adults are co-infected with latent TB.
      Health officials in Brazil have recommended that HIV patients be tested for TB
      infection and given TB prophylaxis (isoniazid) if positive. In practice, although
      Brazil is a model for provision of antiretroviral therapy to patients with
      advanced HIV disease, relatively few such patients receive TB testing and
      prevention services. PURPOSE: We initiated a randomized study of a health
      services intervention to train health personnel in implementation of the
      recommended routine of TB testing and isoniazid prophylaxis. The primary goal is
      to reduce incident TB disease in the HIV clinic population. METHODS: The clinic
      level intervention will be phased in gradually over the study period until all
      clinics have received the intervention. The clinics' order of initiation of
      intervention was randomized and subjected to constraints based on clinic-level
      covariates. This phased intervention cluster-randomized trial required special
      attention to power/sample size calculation and randomization procedures, of which
      we provide the relevant details. RESULTS: Special design considerations accounted
      for within-clinic correlation, variation in the clinic size, time-varying ratio
      of intervention to control clinics and guaranteed post-randomization covariate
      balance. These were successfully implemented for the estimation of power and
      execution of the randomization strategy. LIMITATIONS: Although the design
      features of randomization by clinic and phased implementation of the intervention
      meet logistic and local needs, they substantially lower the statistical power of
      the study. CONCLUSIONS: Studies with cluster-randomized order of intervention
      introduction can provide useful information on intervention effects. Their design
      and analysis are more complicated than for individually randomized parallel
      design trials. The methods we describe represent practical approaches to the
      challenges raised in the course of designing this study.

PMID- 17456523
TI  - Bone mineral density in patients with recently diagnosed, active rheumatoid
      arthritis.
AB  - OBJECTIVES: Osteoporosis is a well-known extra-articular phenomenon in patients
      with uncontrolled, long-standing rheumatoid arthritis (RA). In the present study,
      the extent of osteoporosis and reduced bone mineral density (BMD) and the disease
      related and demographic factors that are associated with osteoporosis and reduced
      BMD were examined in patients with recently diagnosed, active RA. METHODS: BMD of
      the total hip and the lumbar spine was measured using dual-energy x ray
      absorptiometry in 381 patients with recently diagnosed active RA, who had never
      been treated with DMARDs or corticosteroids. Osteoporosis was defined as a T
      score <or=-2.5 SD and reduced BMD as Z score <or=-1 SD. Multivariate logistic
      regression analyses were performed to detect associations of osteoporosis and
      reduced BMD with disease activity, functional disability, joint damage (Sharp-van
      der Heijde score) and demographic factors. RESULTS: Osteoporosis and reduced BMD
      were found in the spine and/or the hip in 11% and 25%, respectively, of the
      patients. Longer symptom duration and presence of rheumatoid factor (RF) were the
      only RA-specific markers for osteoporosis and reduced BMD. Further,
      postmenopausal status in women, a low body mass index, familial osteoporosis,
      and, remarkably, male gender, were independently associated with osteoporosis and
      reduced BMD. CONCLUSION: In patients with recently diagnosed active RA who had
      never been treated with DMARDs or corticosteroids, BMD seems to be well-preserved
      and predominantly related to demographic factors. Longer symptom duration and a
      positive RF, but not higher disease activity or more joint damage, were related
      to osteoporosis and reduced BMD.

PMID- 17456524
TI  - Macrophage migration inhibitory factor polymorphisms do not predict therapeutic
      response to glucocorticoids or to tumour necrosis factor alpha-neutralising
      treatments in rheumatoid arthritis.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is an inflammatory
      mediator associated with RA severity. In various diseases, MIF polymorphisms are
      associated with clinical response glucocorticoid (GC) treatment. It is unclear
      whether MIF polymorphisms determine GC response in rheumatoid arthritis (RA) and
      to other RA treatments. Therefore, the question of whether two functional
      variants in MIF are associated with the response to tumour necrosis factor
      (TNF)alpha-neutralising and GC treatments in RA was investigated. METHODS: Data
      from two cohorts of an RA registry were used. For patients who started with
      TNFalpha-neutralising (infliximab) or GC treatment, courses with a duration of at
      least 3 months were included and response to TNFalpha blockers or GC was
      calculated according to the European League Against Rheumatism response criteria.
      MIF -173G-->C genotyping was achieved using an assay-on-demand allelic
      discrimination assay, and alleles of the CATT repeat element were identified
      using a fluorescently labelled PCR primer and capillary electrophoresis. Logistic
      regression modelling was used for the statistical analysis. RESULTS: In total,
      192 courses of oral prednisone or methylprednisolone injections in 98 patients
      with RA and 90 patients with RA who were on TNFalpha-neutralising treatments were
      documented. In all, 27% of the patients with RA were found to be heterozygous for
      seven CATT repeats (CATT(7)) and 31% were heterozygous for -173C. Respectively,
      4% and 6% of the patients with RA were homozygous for the MIF CATT(7) repeat or
      the MIF -173C allele. Carrier status and homozygosity for CATT(7 )repeat and the
      MIF -173C allele were not associated with response to GC (odds ratios (ORs) close
      to 1) or to TNFalpha-neutralising treatment (ORs close to 2). CONCLUSION: The MIF
      CATT(7) repeat and the MIF-173G-->C functional variant are not strongly
      associated with a decreased clinical response to TNFalpha-neutralising or GC
      treatment in RA.

PMID- 17456525
TI  - Optic neuritis occurring with anti-tumour necrosis factor alpha therapy.
AB  - OBJECTIVE: Various demyelinating disorders have been reported in association with
      anti-tumour necrosis factor alpha (TNFalpha) agents. The objective of this study
      was to review the occurrence, clinical features and outcome of optic neuritis
      (ON) during treatment with anti-TNFalpha agents. METHODS: A PubMed search was
      conducted to identify literature addressing the potential association between
      anti-TNFalpha agents and ON, following our experience with a patient having
      rheumatoid arthritis in whom ON developed while being treated with infliximab.
      RESULTS: 15 patients including the case presented here with ON in whom the
      symptoms developed following TNFalpha antagonist therapy were evaluated. Eight of
      these patients had received infliximab, five had received etanercept and two
      patients had received adalimumab. Among them, nine patients experienced complete
      resolution, and two patients had partial resolution, while four patients
      continued to have symptoms. DISCUSSION: Patients being treated with a TNFalpha
      antagonist should be closely monitored for the development of ophthalmological or
      neurological signs and symptoms. Furthermore, consideration should be given to
      avoiding such therapies in patients with a history of demyelinating disease. If
      clinical evaluation leads to the diagnosis of ON, discontinuation of the
      medication and institution of steroid treatment should be a priority.

PMID- 17456526
TI  - Performance of referral recommendations in patients with chronic back pain and
      suspected axial spondyloarthritis.
AB  - BACKGROUND: Ankylosing spondylitis (AS) and its early form account for up to 5%
      of all patients with chronic back pain. Interest has recently focused on
      shortening the delay of 5-10 years between the appearance of first symptoms and
      the diagnosis of AS, particularly because effective treatments have now become
      available. Referral parameters that are easy for doctors in primary care to apply
      to patients presenting with possible AS could contribute to earlier diagnosis.
      METHODS: Orthopaedists and primary-care doctors were requested to refer patients
      with (1) chronic low back pain (duration >3 months) and (2) onset of back pain
      before <45 years of age to a specialist rheumatology outpatient clinic for
      further diagnostic investigation if at least one of the following screening
      parameters was present: (1) inflammatory back pain, (2) positive human leucocyte
      antigen B27, and (3) sacroiliitis detected by imaging. The final diagnosis was
      made according to expert opinion. RESULTS: In total, 350 referred cases were
      analysed. A diagnosis of definite axial spondyloarthritis (axial SpA), comprising
      established AS and pre-radiographic axial SpA, could be made in 45.4% of all
      referred patients (of which 50.3% were classified as AS and 49.7% as
      preradiographic axial SpA), whereas 45.4% were classified as non-SpA and 9.1% as
      possible SpA. A diagnosis of definite axial SpA could be made in 34.2% if only
      one referral parameter was positive, and in 62.6% if there was >1 positive
      referral parameter. CONCLUSIONS: The proposed referral parameters have proven
      useful when applied in primary care in identifying patients with AS/pre
      radiographic axial SpA among young to middle-aged patients with chronic low back
      pain.

PMID- 17456527
TI  - Predicting poor functional outcome in community-dwelling older adults with knee
      pain: prognostic value of generic indicators.
AB  - BACKGROUND: In longitudinal studies across a range of regional musculoskeletal
      pain syndromes, certain prognostic factors consistently emerge. They are
      "generic" in the sense that they appear to apply regardless of the particular
      anatomical site or underlying cause of the pain. OBJECTIVE: To investigate the
      value of generic indicators of poor functional outcome for knee pain and
      osteoarthritis in the community. METHODS: We conducted a population-based cohort
      study of adults aged >or=50 years with knee pain as part of the Clinical
      Assessment Study (Knee) (CAS(K)). At baseline, participants completed a postal
      questionnaire and attended a research clinic where they completed a further
      questionnaire and underwent structured physical examination and x rays. The 18
      month follow-up was via a self-completed questionnaire. Risk ratios were
      calculated using Cox regression with a fixed time period assigned to each
      participant. RESULTS: In total, 60% of participants experienced a poor outcome at
      18 months. Twelve univariate associations were associated with poor outcome, with
      four variables remaining in the multivariate model (older age, being overweight
      or obese, having possible or probable anxiety, and more severe pain). Using a
      simple unweighted additive risk score (1 point each for age >or=60 years, body
      mass index >or=25 kg/m(2), possible or probable anxiety, Chronic Pain Grade II
      IV), 90% of participants with all four generic indicators were correctly
      classified. CONCLUSIONS: This study has demonstrated that generic prognostic
      indicators can be used to determine the prognosis of older people in the
      community with knee pain.

PMID- 17456528
TI  - Comparison of in vitro-specific blood tests with tuberculin skin test for
      diagnosis of latent tuberculosis before anti-TNF therapy.
AB  - INTRODUCTION: Latent tuberculosis infection (LTBI) is detected with the
      tuberculin skin test (TST) before anti-TNF therapy. We aimed to investigate in
      vitro blood assays with TB-specific antigens (CFP-10, ESAT-6), in immune-mediated
      inflammatory diseases (IMID) for LTBI screening. PATIENTS AND METHODS: Sixty
      eight IMID patients with (n = 35) or without (n = 33) LTBI according to clinico
      radiographic findings or TST results (10 mm cutoff value) underwent cell
      proliferation assessed by thymidine incorporation and PKH-26 dilution assays, and
      IFNgamma-release enzyme-linked immunosorbent spot (ELISPOT) assays with TB
      specific antigens. RESULTS: In vitro blood assays gave higher positive results in
      patients with LTBI than without (p<0.05), with some variations between tests.
      Among the 13 patients with LTBI diagnosed independently of TST results, 5 had a
      negative TST (38.5%) and only 2 a negative blood assays result (15.4%). The 5
      LTBI patients with negative TST results all had positive blood assays results.
      Ten patients without LTBI but with intermediate TST results (6-10 mm) had no
      different result than patients with TST result </=5 mm (p>0.3) and lower results
      than those with LTBI (p<0.05) on CFP-10+ESAT-6 ELISPOT and CFP-10 proliferation
      assays. CONCLUSION: Anti-TB blood assays are beneficial for LTBI diagnosis in
      IMID. Compared with TST, they show a better sensitivity, as seen by positive
      results in 5 patients with certain LTBI and negative TST, and better specificity,
      as seen by negative results in most patients with intermediate TST as the only
      criteria of LTBI. In the absence of clinico-radiographic findings for LTBI, blood
      assays could replace TST for antibiotherapy decision before anti-TNF.

PMID- 17456529
TI  - Contribution of anti-cyclic citrullinated peptide antibody and rheumatoid factor
      to the diagnosis of arthropathy in haemochromatosis.
AB  - OBJECTIVE: To investigate the prevalence of antibodies to cyclic citrullinated
      peptide (anti-CCP) and rheumatoid factor in patients with hereditary
      haemochromatosis (HHC) and to evaluate their diagnostic reliability in
      distinguishing HHC-associated arthropathy from rheumatoid arthritis. METHODS:
      Anti-CCP antibodies and rheumatoid factor levels were determined by ELISA in sera
      from 87 patients with HHC homozygous for the C282Y mutation of the HFE gene, 31
      patients with rheumatoid arthritis and 162 healthy controls. RESULTS: Of the 87
      patients with HHC, 32 (36.8%) had joint involvement. Anti-CCP antibodies were
      detected in only 1 patient (1.1%) with HHC, who had no joint disease, and in
      (1.2%) healthy controls. In total, 18 (58.1%) patients with rheumatoid arthritis
      displayed anti-CCP reactivity (p<0.001). Rheumatoid factor was detected in 10
      (11.5%) patients with HHC compared with 7 (4.3%) healthy control subjects (p =
      0.03) and 21 of 31 (65.6%) patients with rheumatoid arthritis. CONCLUSIONS:
      Testing for anti-CCP antibodies discriminates HHC arthropathy from rheumatoid
      arthritis, as these patients were consistently anti-CCP negative. Thus, HHC
      arthropathy should be considered in the differential diagnosis of CCP-negative
      arthritis.

PMID- 17456530
TI  - Do children born after assisted conception have less risk of developing infantile
      autism?
AB  - BACKGROUND: A Danish population based matched case-control study of perinatal
      risk factors in children with infantile autism has provided some interesting and
      surprising observations regarding infantile autism and children born after
      assisted conception. METHODS AND RESULTS: The cases (461) consisted of all
      children born between 1990 and 1999 and diagnosed with infantile autism in the
      Danish Psychiatric Central Register before February 2001. Matched controls were
      identified in the Danish Civil Registration System. The main exposure measures
      included obstetric risk factors for infantile autism. We found a 59% decreased
      risk for developing infantile autism among children conceived after assisted
      conception (odds ratio [OR] 0.41, 95% [0.19-0.89]) and a 63% decreased risk after
      adjusting for known risk factors for assisted conception and infantile autism (OR
      0.37, 95% [0.14-0.98]). CONCLUSION: We found that children born after assisted
      conception had a lower risk of developing infantile autism then their matched
      controls. Our observations could possibly be explained by the mother's health
      status before and during early pregnancy. Our findings require further
      investigation in larger studies.

PMID- 17456531
TI  - Computerized assessment of surgical patients for tobacco use: accuracy and
      acceptability.
AB  - BACKGROUND: Despite increased risks of postoperative complications among patients
      who use tobacco, a number of barriers hinder the systematic identification of
      surgical patients who smoke. The study investigated the accuracy and
      acceptability of a patient-completed touchscreen computer program, which assessed
      patient smoking status during attendance at a surgical pre-operative clinic.
      METHODS: One thousand and four patients participated in the study and completed a
      touchscreen computer smoking assessment program. RESULTS: The sensitivity and
      specificity measures of the computerized assessment were 93% and 95%
      respectively. Patients, and clinic receptionists, nurses and anaesthetists found
      the touchscreen computer-based assessment acceptable. CONCLUSIONS: The findings
      suggest that computerized assessment of smoking status is an accurate and
      acceptable way to identify tobacco users in a pre-operative clinic setting.

PMID- 17456532
TI  - Mortality from all causes and circulatory disease by country of birth in England
      and Wales 2001-2003.
AB  - BACKGROUND: Differences in mortality by country of birth in England and Wales in
      people under 70 years of age have been demonstrated previously. Changes in age
      distribution of migrants and in migration patterns have occurred subsequently.
      METHODS: All-cause and circulatory disease mortality for people aged 20 years and
      over in England and Wales by country of birth were examined using population data
      from the 2001 Census and mortality data for 2001-2003. Indirect standardization
      was used to estimate sex-specific standardized mortality ratios (SMRs) and 95%
      confidence intervals (CI) in comparison to mortality for England and Wales as a
      whole. RESULTS: SMRs for all-cause mortality were statistically significantly
      higher than the national average for people born in Ireland, Scotland, East
      Africa and West Africa and lower for people born in China and Hong Kong. SMRs for
      circulatory disease were highest among people born in Bangladesh and lowest among
      people born in China and Hong Kong. Patterns of ischaemic heart disease and
      cerebrovascular disease mortality differed by country of birth. CONCLUSIONS:
      Mortality, particularly due to ischaemic heart disease and stroke, differs
      markedly by country of birth in all age groups including the > or =70-year-old
      group.

PMID- 17456533
TI  - Single-centre experience on endocardial and epicardial pacemaker system function
      in neonates and infants.
AB  - AIMS: Endocardial (ENDO) or epicardial (EPI) pacing systems are implanted in
      infants but it remains unclear which system should be preferred. METHODS AND
      RESULTS: We evaluated the results of children <or=1 year who underwent pacemaker
      (PM) implantation at our centre with a retrospective analysis. Between 1992 and
      2004, 56 patients, 37 of whom had other congenital heart defects (CHDs), received
      a PM at 4.4 +/- 3.8 months of age for atrioventricular block (n = 52) and sinus
      node dysfunction. Rate-responsive ventricular demand pacing (VVIR) PMs were
      implanted in 25 patients (19 ENDO), dual-chamber demand pacing (DDD) in 29, and
      rate-responsive atrial demand pacing (AAIR) in 2 (all EPI). Follow-up (FU) was
      4.5 +/- 3.5 (range 0.3-13) years: 15 pacing system failures occurred among the 56
      patients (26%) after 4.5 +/- 3.2 years, with a significantly reduced success rate
      for EPI (21-fold increase of the risk of failure) and complex CHD. Also in
      patients without surgery for CHD, EPI showed a worse outcome. Among the 91 leads
      implanted, failures occurred more significantly in EPI (18% of atrial, 24% of
      ventricular leads) than in ENDO (5% of ventricular leads). No venous occlusion
      was found at FU. CONCLUSIONS: Single-lead, VVIR ENDO pacing had higher efficiency
      and safety than EPI, and it might be the best choice for PM implantation in
      infants. However, because of small patient numbers and lack of longer FU, these
      findings should be treated with caution.

PMID- 17456534
TI  - Comment: Community pharmacy services in Portugal.

PMID- 17456536
TI  - A key to the literature of total parenteral nutrition. 1983.

PMID- 17456537
TI  - The availability of trace elements in intravenous hyperalimentation solutions.
      1977.

PMID- 17456538
TI  - Advancement of nutrition support in clinical pharmacy.

PMID- 17456539
TI  - Use of bone health protocol to identify and prevent bone disease in kidney and
      pancreas transplant recipients.
AB  - BACKGROUND: Posttransplant bone disease is a well recognized and undertreated
      problem. The use of protocols within other populations has been shown to improve
      recognition and treatment of common disease states, but outcome studies involving
      the use of protocols within transplant patients are lacking. OBJECTIVE: To
      compare the appropriate screening for and the prevention and treatment of
      osteopenia and osteoporosis in transplant patients before and after a bone health
      protocol was implemented. METHODS: A retrospective analysis in a single
      institution was designed to determine whether the development and implementation
      of a comprehensive bone health protocol impacted disease outcomes in
      posttransplant kidney and simultaneous kidney-pancreas patients. RESULTS: There
      were 132 patients in the historical control group and 76 in the treatment group.
      The groups were well matched, with no statistically significant differences noted
      for any of the baseline characteristics that were compared, including the
      modifiable and nonmodifiable risk factors known to put a patient at increased
      risk for osteopenia or osteoporosis. Significantly more patients in the treatment
      group received proper screening and prevention compared with the historical
      control group (p < 0.001). Although more patients in the treatment group received
      proper bone disease treatment, this did not reach statistical significance (81%
      vs 66%; p < 0.22). Additionally, the dual energy X-ray absorptiometry scans were
      performed, on average, 19 days earlier in the treatment group, although this also
      did not achieve statistical significance (p = 0.149). CONCLUSIONS: The
      multidisciplinary development and implementation of a comprehensive bone health
      protocol improves the screening and prevention of osteopenia and osteoporosis
      within kidney and pancreas transplant recipients.

PMID- 17456540
TI  - Providing patient care through community pharmacies in the UK: policy, practice,
      and research.
AB  - OBJECTIVE: To describe the provision of patient services through community
      pharmacies in the UK, with particular reference to England, and to explore the
      research evidence and policy developments for enhancing the contribution of
      community pharmacy to primary care and public health. FINDINGS: In the UK,
      National Health Service (NHS) pharmaceutical services are delivered under
      contract by privately owned community pharmacies. In England, a new 3 tier
      structure for pharmaceutical services was introduced in 2005 comprising
      essential, advanced, and enhanced-level services. All NHS pharmacies must deliver
      7 essential pharmaceutical services and provide evidence that they meet the
      requirements of a comprehensive quality assurance framework. In the first year of
      the contract, around 40% of pharmacies were accredited to undertake medicine use
      reviews, the first advanced-level service to be implemented. Meanwhile, up to 25%
      of pharmacies provide a variety of enhanced-level services; the most common of
      these is supervised administration of methadone as well as support programs for
      patients quitting smoking. New legislation is being introduced that will
      accomplish the following: allow pharmacists to acquire independent prescribing
      rights, require pharmacy technicians to be licensed, necessitate that both
      pharmacists and pharmacy technicians periodically demonstrate their continuing
      qualification to practice, and introduce the concept of the "responsible
      pharmacist" to the operation of community pharmacies. DISCUSSION: Community
      pharmacy is now being recognized by the government as a mainstream contributor to
      primary care and public health. The current priority is to integrate services
      provided through community pharmacies into programs provided by other primary
      care professionals, through strengthening information technology and contractual
      arrangements. While major changes to the regulation of the pharmacy workforce are
      occurring, the quality management of community pharmacy services merits further
      attention. CONCLUSIONS: The new NHS pharmacy contract and current legislative
      changes provide a basis for community pharmacy to become fully integrated into
      NHS long-term care and public health programs.

PMID- 17456541
TI  - Etanercept for toxic epidermal necrolysis.

PMID- 17456542
TI  - Adverse effects of voriconazole: analysis of the French Pharmacovigilance
      Database.
AB  - BACKGROUND: The most common adverse effects of voriconazole reported during
      clinical trials were disturbances of vision (30% of pts.), skin rashes (17.3%),
      and elevations in hepatic enzymes level (approximately 10% of pts.; varying with
      enzymes). However, postmarketing data concerning safety of voriconazole are
      limited. OBJECTIVE: To describe voriconazole adverse drug effects (ADEs) after 4
      years of the drug's availability in France and determine their occurrence.
      METHODS: All cases of ADEs including voriconazole reported to the French
      Pharmacovigilance Database between 2002 and 2005 were analyzed. For each case,
      the following data were recorded: age, sex, indication, concomitant disease,
      concomitant medications, and ADE description. Causality link between voriconazole
      and ADEs was performed using the Naranjo probability scale. RESULTS: A total of
      227 ADE cases were reported in 178 adults and 9 children (<12 y), with 66%
      occurring in males. The patients' median age was 49.6 (2-80) years. ADEs included
      liver function test abnormalities (23%), visual disturbances (18%), skin rashes
      (17%), neurologic disturbances (14%), cardiovascular events (10%), hematologic
      disorders (8%), and renal disturbances (4%). Other less commonly identified ADEs
      included headache, nausea, vomiting, and diarrhea. Drug-drug interactions were
      observed in 7 cases. According to the Naranjo criteria, 84% of ADEs were
      classified as possible, 7% as probable, 5% as highly probable, and 4% as
      doubtful. CONCLUSIONS: Most ADEs found in this study are well documented in the
      literature, except for cardiac complications, which are rarely reported. Few ADEs
      related to drug interactions were observed; however, due to the extensive
      metabolism of voriconazole by cytochrome P450 isoenzymes, clinicians should be
      aware of potential interactions between voriconazole and other drugs metabolized
      through this pathway.

PMID- 17456543
TI  - Managing complex medication regimens: perspectives of consumers with
      osteoarthritis and healthcare professionals.
AB  - BACKGROUND: Managing medications is complex, particularly for consumers with
      multiple coexisting conditions for whom benefits and adverse effects are
      unpredictable and health priorities may be variable. OBJECTIVE: To investigate
      perceptions of and experiences with managing drug regimens from the perspectives
      of consumers with osteoarthritis and coexisting chronic conditions and of
      healthcare professionals from diverse backgrounds. METHODS: Using an exploratory
      research design, focus groups were formed with 34 consumers and 19 healthcare
      professionals. Individual interviews were undertaken with 3 community medical
      practitioners. RESULTS: Consumers' management of medications was explored in
      terms of 3 themes: administration of medications, provision of information, and
      the perceived role of healthcare professionals. In general, consumers lacked
      understanding regarding the reason that they were prescribed certain medications.
      Since all consumer participants had at least 2 chronic conditions, they were
      taking many drugs to relieve undesirable symptoms. Some consumers were unable to
      achieve improved pain relief and were reluctant to take analgesics prescribed on
      an as-needed basis. Healthcare professionals discussed the importance of using
      non-pharmacologic measures to improve symptoms; however, consumers stated that
      physicians encourage them to continue using medications, often for prolonged
      periods, even when these agents are not helpful. CONCLUSIONS: Consumers were
      dissatisfied about the complexity of their medication regimens and also lacked
      understanding as to how to take their drugs effectively. Dedicated time should be
      devoted during medical consultations to facilitate verbal exchange of information
      about medications. Pharmacists must communicate regularly with physicians about
      consumers' medication needs to help preempt any problems that may arise.
      Instructions need to be revised through collaboration between physicians and
      pharmacists so that "as needed" directions provide more explicit advice about
      when and how to use such drugs. Future research, using large, generalizable
      samples, should examine trends related to consumers' experiences of symptomatic
      relief from chronic conditions and their understandings about medications.

PMID- 17456544
TI  - Aspirin resistance in patients with stable coronary artery disease with and
      without a history of myocardial infarction.
AB  - BACKGROUND: Aspirin therapy is a cornerstone in the prevention of
      atherothrombotic events, but recurrent vascular events are estimated to occur in
      8-18% of patients taking aspirin for secondary prevention after 2 years.
      Estimates of biologic aspirin resistance vary from 5% to 60%, depending on the
      assay used. However, the relationship between biologic measurements of aspirin
      resistance and adverse clinical events remains unclear. OBJECTIVE: To determine
      whether patients with documented myocardial infarction (MI) while on aspirin
      therapy (cases) were more likely to be aspirin resistant than were patients with
      coronary artery disease (CAD) who had no history of MI (controls) and to assess
      clinical predictors of aspirin resistance in patients with stable CAD. METHODS:
      This case-control study examined aspirin responses using the VerifyNow Aspirin
      Assay system in 50 cases and 50 controls who had taken a dose of aspirin within
      48 hours of presentation to the clinic visit. Odds ratios were estimated to
      determine the association between aspirin resistance and MI. Independent
      predictors of aspirin resistance were determined using univariate and
      multivariate analyses. RESULTS: An increase in the prevalence of aspirin
      resistance among cases (16% vs 12% in controls) was not observed (OR 1.40; 95% CI
      0.45 to 4.37; p = 0.566). In the overall CAD population, female sex was
      independently associated with aspirin resistance (OR 4.01; 95% CI 1.15 to 13.92;
      p = 0.029). CONCLUSIONS: Additional large studies are required to understand
      whether biologically defined aspirin resistance is associated with increased risk
      for cardiovascular events, with special attention paid to sex differences.

PMID- 17456546
TI  - Shock wave therapy for chronic plantar fasciopathy.
AB  - INTRODUCTION: Relevant data of randomized-controlled studies on shock wave
      treatment for chronic plantar fasciopathy are statistically and clinically
      heterogeneous. METHODS: Randomized trials were identified form a current search
      of the Cochrane Bone, Joint and Muscle Trauma Group specialized register of
      trials, the Cochrane Central Register of Controlled Trials, MEDLINE and reference
      lists of articles and dissertations. We identified and retrieved a total of 17
      articles. Methodological quality criterial included appropriate randomization,
      allocation concealment, blinding, number lost of follow-up and intention to treat
      analysis. Significant heterogeneity between studies precluded pooled analyses.
      Instead, individual trial results were described in the text. RESULTS: We
      identified conflicting results in the 17 studies, involving more than 2100
      participants. There was considerable heterogeneity in terms of methodological
      quality, treatment regimen, patient selection and follow-up period. CONCLUSIONS:
      With current studies heterogenous in terms of the duration of the disorder; type,
      frequency and total dose of shock wave therapy (SWT); period of time between SWT;
      type of management and control group; timing of follow-up and outcomes assessed,
      a pooled meta-analysis of SWT for chronic plantar fasciopathy was considered
      inappropriate. Neverhteless, there was a preponderance of well-designed studies
      showing favourable results. It appears that one should only consider SWT for
      plantar fasciopathy after more common, accepted and proven non-invasive
      treatments have failed.

PMID- 17456545
TI  - The role of vildagliptin in the management of type 2 diabetes mellitus.
AB  - OBJECTIVE: To highlight the role of incretin hormones in the management of type 2
      diabetes mellitus with a focus on vildagliptin, a dipeptidyl peptidase IV (DPP
      IV) inhibitor currently in development. DATA SOURCES: Searches were conducted in
      MEDLINE (1950-April 2007) and International Pharmaceutical Abstracts (1970-April
      2007) using the key words vildagliptin, LAF237, and dipeptidyl peptidase IV
      inhibitor. Additional data were obtained from abstracts presented at the American
      Diabetes Association Scientific Sessions (2003-2006) and from the manufacturer.
      STUDY SELECTION AND DATA EXTRACTION: Articles pertaining to the pharmacology,
      pharmacokinetics, safety, and efficacy of vildagliptin for the treatment of type
      2 diabetes were reviewed for inclusion. When available, human trials were
      included over animal studies. DATA SYNTHESIS: Reduced incretin effect is thought
      to be associated with type 2 diabetes. Glucagon-like peptide-1 (GLP-1), an
      incretin hormone, stimulates postprandial insulin release; however, it is rapidly
      degraded by DPP IV. Studies evaluating the use of vildagliptin in patients with
      type 2 diabetes found significant decreases in DPP IV and increased GLP-1
      activity 45 minutes after dosing. Glucagon levels were reduced, with little to no
      change in insulin levels. With vildagliptin doses ranging from 25 mg daily to 100
      mg twice daily, researchers observed consistent reductions in fasting plasma
      glucose, 4 hour postprandial glucose, and hemoglobin A1c. Similar benefits were
      seen when vildagliptin was used in combination with metformin. Vildagliptin was
      well tolerated after 12 weeks; however, incidences of hypoglycemia increased with
      longer study duration. Optimal results with minimal adverse effects were achieved
      with 25 mg twice daily and 50 mg once daily doses. CONCLUSIONS: Vildagliptin
      represents a safe and effective new approach to targeting GLP-1 deficiencies in
      patients with type 2 diabetes by inhibiting DPP IV.

PMID- 17456547
TI  - F-actin binding is essential for coronin 1B function in vivo.
AB  - Coronins are conserved F-actin binding proteins that have been implicated in a
      variety of processes including fibroblast migration, phagocytosis, and
      chemotaxis. Recent data from our lab indicate that coronin 1B coordinates Arp2/3
      dependent actin filament nucleation and cofilin-mediated filament turnover at the
      leading edge of migrating fibroblasts. Analysis of coronin function has been
      hampered by the lack of a clear understanding of how coronin interacts with F
      actin. Here, we identify a surface-exposed conserved arginine residue at position
      30 (R30), which is crucial for coronin 1B binding to F-actin both in vitro and in
      vivo. Using actin co-sedimentation, we demonstrate that coronin 1B binds with
      high affinity to ATP/ADP-P(i)-F-actin (170 nM) and with 47-fold lower affinity to
      ADP-F-actin (8 microM). In contrast to a previous study, we find no evidence for
      enhanced cofilin binding to F-actin in the presence of either coronin 1B or
      coronin 1A. Instead, we find that coronin 1B protects actin filaments from
      cofilin-induced depolymerization. Consistent with an important role for
      interactions between coronin 1B and F-actin in vivo, an R30D coronin mutant that
      does not bind F-actin localizes inefficiently to the leading edge. Furthermore,
      our analysis indicates that F-actin binding is absolutely required for coronin 1B
      to exert its effects on whole-cell motility and lamellipodial dynamics.

PMID- 17456548
TI  - Characterization of Spo11-dependent and independent phospho-H2AX foci during
      meiotic prophase I in the male mouse.
AB  - Meiotic DNA double strand breaks (DSBs) are indicated at leptotene by the
      phosphorylated form of histone H2AX (gamma-H2AX). In contrast to previous
      studies, we identified on both zygotene and pachytene chromosomes two distinct
      types of gamma-H2AX foci: multiple small (S) foci located along autosomal
      synaptonemal complexes (SCs) and larger signals on chromatin loops (L-foci). The
      S-foci number gradually declined throughout pachytene, in parallel with the
      repair of DSBs monitored by repair proteins suggesting that S-foci mark DSB
      repair events. We validated this interpretation by showing the absence of S-foci
      in Spo11(-/-) spermatocytes. By contrast, the L-foci number was very low through
      pachytene. Based on the analysis of gamma-H2AX labeling after irradiation of
      spermatocytes, the formation of DSBs clearly induced L-foci formation. Upon DSB
      repair, these foci appear to be processed and lead to the above mentioned S-foci.
      The presence of L-foci in wild-type pachytene and diplotene could therefore
      reflect delayed or unregulated DSB repair events. Interestingly, their
      distribution was different in Spo11(+/-) spermatocytes compared with Spo11(+/+)
      spermatocytes, where DSB repair might be differently regulated as a response to
      homeostatic control of crossing-over. The presence of these L-foci in Spo11(-/-)
      spermatocytes raises the interesting possibility of yet uncharacterized
      alterations in DNA or chromosome structure in Spo11(-/-) cells.

PMID- 17456549
TI  - Phosphoinositide 3-kinase signalling regulates early development and
      developmental haemopoiesis.
AB  - Phosphoinositide 3-kinase (PI3K)-dependent signalling regulates a wide variety of
      cellular functions including proliferation and differentiation. Disruption of
      class I(A) PI3K isoforms has implicated PI3K-mediated signalling in development
      of the early embryo and lymphohaemopoietic system. We have used embryonic stem
      (ES) cells as an in vitro model to study the involvement of PI3K-dependent
      signalling during early development and haemopoiesis. Both pharmacological
      inhibition and genetic manipulation of PI3K-dependent signalling demonstrate that
      PI3K-mediated signals, most likely via 3-phosphoinositide-dependent protein
      kinase 1 (PDK1), are required for proliferation of cells within developing
      embryoid bodies (EBs). Surprisingly, the haemopoietic potential of EB-derived
      cells was not blocked upon PI3K inhibition but rather enhanced, correlating with
      modest increases in expression of haemopoietic marker genes. By contrast, PDK1
      deficient EB-derived progeny failed to generate terminally differentiated
      haemopoietic lineages. This deficiency appeared to be due to a requirement for
      PI3K signalling during the proliferative phase of blast-colony-forming cell (BL
      CFC) expansion, rather than as a result of effects on differentiation per se. We
      also demonstrate that PI3K-dependent signalling is required for optimal
      generation of erythroid and myeloid progenitors and their differentiation into
      mature haemopoietic colony types. These data demonstrate that PI3K-dependent
      signals play important roles at different stages of haemopoietic development.

PMID- 17456550
TI  - Cortical centralspindlin and G alpha have parallel roles in furrow initiation in
      early C. elegans embryos.
AB  - Evidence from various systems suggests that either asters or the midzone of the
      mitotic spindle are the predominant determinants of cleavage plane position.
      Disrupting spindle midzone formation in the one-cell Caenorhabditis elegans
      embryo, such as by using mutants of the centralspindlin component ZEN-4, prevents
      completion of cytokinesis but does not inhibit furrowing. However, furrowing is
      inhibited by the simultaneous depletion of ZEN-4 with either PAR-2 or G alpha,
      which are required for asymmetric divisions. Through studies of other genes
      required for the presence of an intact spindle midzone containing microtubule
      bundles, we found that furrowing failed in the absence of PAR-2 or G alpha only
      when centralspindlin was absent from the furrow. We also found spindle length or
      microtubule distribution did not correlate with furrow initiation. We propose
      that centralspindlin acts redundantly with G alpha to regulate furrow initiation.

PMID- 17456551
TI  - Src-dependent phosphorylation of beta2-adaptin dissociates the beta-arrestin-AP-2
      complex.
AB  - Beta-arrestins are known to act as endocytic adaptors by recruiting the clathrin
      adaptor protein 2 (AP-2) complex to G-protein-coupled receptors (GPCRs), linking
      them to clathrin-coated pits (CCPs) for internalization. They also act as
      signaling molecules connecting GPCRs to different downstream effectors. We have
      previously shown that stimulation of the angiotensin II (Ang II) type 1 receptor
      (AGTR1, hereafter referred to as AT1R), a member of the GPCR family, promotes the
      formation of a complex between beta-arrestin, the kinase Src and AP-2. Here, we
      report that formation of such a complex is involved in the AT1R-mediated tyrosine
      phosphorylation of beta2-adaptin, the subunit of AP-2 involved in binding beta
      arrestin. We identify a crucial tyrosine residue in the ear domain of beta2
      adaptin and show in vitro that the phosphorylation of this site regulates the
      interaction between beta-arrestin and beta2-adaptin. Using fluorescently tagged
      proteins combined with resonance energy transfer and image cross-correlation
      spectroscopy approaches, we show in live cells that beta2-adaptin phosphorylation
      is an important regulatory process for the dissociation of beta-arrestin-AP-2
      complexes in CCPs. Finally, we show that beta2-adaptin phosphorylation is
      involved in the early steps of receptor internalization. Our findings not only
      unveil beta2-adaptin as a new Src target during AT1R internalization, but also
      support the role of receptor-mediated signaling in the control of clathrin
      dependent endocytosis of receptors.

PMID- 17456552
TI  - Post-translational integration of tail-anchored proteins is facilitated by
      defined molecular chaperones.
AB  - Tail-anchored (TA) proteins provide an ideal model for studying post
      translational integration at the endoplasmic reticulum (ER) of eukaryotes. There
      are multiple pathways for delivering TA proteins from the cytosol to the ER
      membrane yet, whereas an ATP-dependent route predominates, none of the cytosolic
      components involved had been identified. In this study we have directly addressed
      this issue and identify novel interactions between a model TA protein and the two
      cytosolic chaperones Hsp40 and Hsc70. To investigate their function, we have
      reconstituted the membrane integration of TA proteins using purified components.
      Remarkably, we find that a combination of Hsc70 and Hsp40 can completely
      substitute for the ATP-dependent factors present in cytosol. On the basis of this
      in vitro analysis, we conclude that this chaperone pair can efficiently
      facilitate the ATP-dependent integration of TA proteins.

PMID- 17456553
TI  - Force activates smooth muscle alpha-actin promoter activity through the Rho
      signaling pathway.
AB  - In pressure or volume overload, hypertrophic growth of the myocardium is
      associated with myofibroblast differentiation, a process in which cardiac
      fibroblasts express smooth muscle alpha-actin (SMA). The signaling mechanisms
      that mediate force-induced myofibroblast differentiation and SMA expression are
      not defined. We examined the role of the Rho-Rho-kinase pathway in force-induced
      SMA expression in fibroblasts using an in vitro model system that applies static
      tensile forces (0.65 pN/microm(2)) to integrins via collagen-coated magnetite
      beads. Force maximally induced RhoA activation at 10 minutes that was localized
      to force application sites and required intact actin filaments. Force application
      induced phosphorylation of LIM kinase (5-10 minutes) and an early
      dephosphorylation of cofilin (5 minutes) that was followed by prolonged cofilin
      phosphorylation. These responses were blocked by Y27632, an inhibitor of Rho
      kinase. Force promoted actin filament assembly at force application sites (10-20
      minutes), a process that required Rho kinase and cofilin. Force application
      induced nuclear translocation of the transcriptional co-activator MRTF-A but not
      MRTF-B. Nuclear translocation of MRTF-A required Rho kinase and intact actin
      filaments. Force caused 3.5-fold increases of SMA promoter activity that were
      completely blocked by transfection of cells with dominant-negative MRTF-A or by
      inhibition of Rho kinase or by actin filament disassembly. These data indicate
      that mechanical forces mediate actin assembly through the Rho-Rho-kinase-LIMK
      cofilin pathway. Force-mediated actin filament assembly promotes nuclear
      translocation of MRTF and subsequent activation of the SMA promoter to enhance
      SMA expression.

PMID- 17456554
TI  - A multicenter comparison of tap water versus sterile saline for wound irrigation.
AB  - OBJECTIVES: To compare wound infection rates for irrigation with tap water versus
      sterile saline before closure of wounds in the emergency department. METHODS: The
      study was a multicenter, prospective, randomized trial conducted at two Level 1
      urban hospitals and a suburban community hospital. Subjects were a convenience
      sample of adults presenting with acute simple lacerations requiring sutures or
      staples. Subjects were randomized to irrigation in a sink with tap water or with
      normal saline using a sterile syringe. Wounds were closed in the standard
      fashion. Subjects were asked to return to the emergency department for suture
      removal. Those who did not return were contacted by telephone. Wounds were
      considered infected if there was early removal of sutures or staples, if there
      was irrigation and drainage of the wound, or if the subject needed to be placed
      on antibiotics. Equivalence of the groups was met if there was less than a
      doubling of the infection rate. RESULTS: A total of 715 subjects were enrolled in
      the study. Follow-up data were obtained on 634 (88%) of enrolled subjects. Twelve
      (4%) of the 300 subjects in the tap water group had wound infections, compared
      with 11 (3.3%) of the 334 subjects in the saline group. The relative risk was
      1.21 (95% confidence interval = 0.5 to 2.7). CONCLUSIONS: Equivalent rates of
      wound infection were found using either irrigant. The results of this multicenter
      trial evaluating tap water as an irrigant agree with those from previous single
      institution trials.

PMID- 17456555
TI  - The epidemiology of emergency medical services use by older adults: an analysis
      of the National Hospital Ambulatory Medical Care Survey.
AB  - OBJECTIVES: To characterize older adult emergency department (ED) visits arriving
      by emergency medical services (EMS) and to identify factors associated with those
      patient visits. METHODS: A secondary analysis of the ED component of the 1997
      2000 National Hospital Ambulatory Medical Care Survey using logistic regression
      analyses was conducted. The dependent variable was the modes of arrival (EMS vs.
      not EMS) to the ED. Independent variables were grouped into four domains:
      demographic, clinical, system, and service characteristics. RESULTS: Between 1997
      and 2000, 38% of EMS responses were for patients aged 65 years and older. During
      that period, 62.2 million older adult ED patient visits occurred; 38% arrived via
      EMS. The average rate of EMS utilization by older adults was 167/1,000 population
      per year, more than four times the rate for younger patients (39/1,000
      population). Fifty-three percent of EMS responses with transport to an ED for
      older adults resulted in hospital admission. Factors found to be associated with
      EMS mode of arrival included demographic (older age and urban residence),
      clinical (need for more rapid care and circulatory system illnesses), and service
      (need for procedures). CONCLUSIONS: Older adults account for a large proportion
      of EMS responses and use EMS at a disproportionately high rate. As the older
      adult population grows, EMS systems must prepare for the increased volume of
      older adults by making changes in training, operations, and equipment.

PMID- 17456556
TI  - Can academic emergency medicine influence the growth of emergency medicine
      globally?

PMID- 17456557
TI  - The search for common ground: developing emergency medicine in Iran.
AB  - Academic ties between Iran and the United States were extensive before the 1979
      revolution in Iran. After 20 years of negligible academic exchanges, there has
      been a growing trend of professional contacts between the two countries over the
      past few years. The genuine warmth of friendship and commitment to excellence in
      emergency medicine (EM) among Iranians has transcended the political barriers to
      allow international contribution of EM development in the country. Since 1999,
      there has been a successful academic collaboration between Iranian and U.S.
      universities to help develop EM in Iran. Today, remarkable progresses have been
      achieved through recognition of EM as a distinct profession, developing EM
      residency programs, improving emergency medical services, establishing qualified
      emergency departments, training faculty and staff, starting physician exchange
      programs, and building mutual contributions with professionals throughout the
      world. A supportive policy environment and a high-quality health care system have
      had incredible impacts on EM development in the country.

PMID- 17456558
TI  - Chronicles of an emergency medicine intern.

PMID- 17456559
TI  - Commentary: Physician well-being: the seventh competency?

PMID- 17456560
TI  - The use of the Broselow tape in pediatric resuscitation.

PMID- 17456562
TI  - RNA-based affinity purification reveals 7SK RNPs with distinct composition and
      regulation.
AB  - Recent studies have uncovered an unanticipated diversity of noncoding RNAs
      (ncRNAs), although these studies provide limited insight into their biological
      significance. Numerous general methods for identification and characterization of
      protein interactions have been developed, but similar approaches for
      characterizing cellular ncRNA interactions are lacking. Here we describe RNA
      Affinity in Tandem (RAT), an original, entirely RNA tag-based method for affinity
      purification of endogenously assembled RNP complexes. We demonstrate the general
      utility of RAT by isolating RNPs assembled in vivo on ncRNAs transcribed by RNA
      polymerase II or III. Using RAT in conjunction with protein identification by
      mass spectrometry and protein-RNA interaction assays, we define and characterize
      previously unanticipated protein subunits of endogenously assembled human 7SK
      RNPs. We show that 7SK RNA resides in a mixed population of RNPs with different
      protein compositions and responses to cellular stress. Depletion of a newly
      identified 7SK RNP component, hnRNP K, alters the partitioning of 7SK RNA among
      distinct RNPs. Our results establish the utility of a generalizable RNA-based RNP
      affinity purification method and provide insight into 7SK RNP dynamics.

PMID- 17456563
TI  - A rapid, quantitative assay for direct detection of microRNAs and other small
      RNAs using splinted ligation.
AB  - The discovery and characterization of microRNAs (miRNAs) and other families of
      short RNAs has led to a rapid expansion of research directed at elucidating their
      expression patterns and regulatory functions. Here, we describe a convenient,
      sensitive, and straightforward method to detect and quantitate specific miRNA
      levels in unfractionated total RNA samples. The method, based on splinted
      ligation, does not require specialized equipment or any amplification step, and
      is significantly faster and more sensitive than Northern blotting. We demonstrate
      that the method can be used to detect various classes of small regulatory RNAs
      from different organisms.

PMID- 17456564
TI  - A case for "StopGo": reprogramming translation to augment codon meaning of GGN by
      promoting unconventional termination (Stop) after addition of glycine and then
      allowing continued translation (Go).
AB  - When a eukaryotic mRNA sequence specifying an amino acid motif known as 2A is
      directly followed by a proline codon, two nonoverlapping proteins are
      synthesized. From earlier work, the second protein is known to start with this
      proline codon and is not created by proteolysis. Here we identify the C-terminal
      amino acid of an upstream 2A-encoded product from Perina nuda picorna-like virus
      that is glycine specified by the last codon of the 2A-encoding sequence. This is
      an example of recoding where 2A promotes unconventional termination after
      decoding of the glycine codon and continued translation beginning with the 3'
      adjacent proline codon.

PMID- 17456565
TI  - A recoding element that stimulates decoding of UGA codons by Sec tRNA[Ser]Sec.
AB  - Selenocysteine insertion during decoding of eukaryotic selenoprotein mRNA
      requires several trans-acting factors and a cis-acting selenocysteine insertion
      sequence (SECIS) usually located in the 3' UTR. A second cis-acting
      selenocysteine codon redefinition element (SRE) has recently been described that
      resides near the UGA-Sec codon of selenoprotein N (SEPN1). Similar
      phylogenetically conserved elements can be predicted in a subset of eukaryotic
      selenoprotein mRNAs. Previous experimental analysis of the SEPN1 SRE revealed it
      to have a stimulatory effect on readthrough of the UGA-Sec codon, which was not
      dependent upon the presence of a SECIS element in the 3' UTR; although, as
      expected, readthrough efficiency was further elevated by inclusion of a SECIS. In
      order to examine the nature of the redefinition event stimulated by the SEPN1
      SRE, we have modified an experimentally tractable in vitro translation system
      that recapitulates efficient selenocysteine insertion. The results presented here
      illustrate that the SRE element has a stimulatory effect on decoding of the UGA
      Sec codon by both the methylated and unmethylated isoforms of Sec tRNA([Ser]Sec),
      and confirm that efficient selenocysteine insertion is dependent on the presence
      of a 3'-UTR SECIS. The variation in recoding elements predicted near UGA-Sec
      codons implies that these elements may play a differential role in determining
      the amount of selenoprotein produced by acting as controllers of UGA decoding
      efficiency.

PMID- 17456566
TI  - Distinct reaction pathway promoted by non-divalent-metal cations in a tertiary
      stabilized hammerhead ribozyme.
AB  - Divalent ion sensitivity of hammerhead ribozymes is significantly reduced when
      the RNA structure includes appropriate tertiary stabilization. Therefore, we
      investigated the activity of the tertiary stabilized "RzB" hammerhead ribozyme in
      several nondivalent ions. Ribozyme RzB is active in spermidine and Na(+) alone,
      although the cleavage rates are reduced by more than 1,000-fold relative to the
      rates observed in Mg(2+) and in transition metal ions. The trivalent cobalt
      hexammine (CoHex) ion is often used as an exchange-inert analog of hydrated
      magnesium ion. Trans-cleavage rates exceeded 8 min(-1) in 20 mM CoHex, which
      promoted cleavage through outersphere interactions. The stimulation of catalysis
      afforded by the tertiary structural interactions within RzB does not require
      Mg(2+), unlike other extended hammerhead ribozymes. Site-specific interaction
      with at least one Mg(2+) ion is suggested by CoHex competition experiments. In
      the presence of a constant, low concentration of Mg(2+), low concentrations of
      CoHex decreased the rate by two to three orders of magnitude relative to the rate
      in Mg(2+) alone. Cleavage rates increased as CoHex concentrations were raised
      further, but the final fraction cleaved was lower than what was observed in CoHex
      or Mg(2+) alone. These observations suggest that Mg(2+) and CoHex compete for
      binding and that they cause misfolded structures when they are together. The
      results of this study support the existence of an alternate catalytic mechanism
      used by nondivalent ions (especially CoHex) that is distinct from the one
      promoted by divalent metal ions, and they imply that divalent metals influence
      catalysis through a specific nonstructural role.

PMID- 17456567
TI  - A familial thyrotropin (TSH) receptor mutation provides in vivo evidence that the
      inositol phosphates/Ca2+ cascade mediates TSH action on thyroid hormone
      synthesis.
AB  - CONTEXT: In the human thyroid gland, TSH activates both the cAMP and inositol
      phosphates (IP) signaling cascades via binding to the TSH receptor (TSHR).
      Biallelic TSHR loss-of-function mutations cause resistance to TSH, clinically
      characterized by hyperthyrotropinemia, and normal or reduced thyroid gland
      volume, thyroid hormone output, and iodine uptake. OBJECTIVE: We report and study
      a novel familial TSHR mutation (L653V). RESULTS: Homozygous individuals
      expressing L653V had euthyroid hyperthyrotropinemia. Paradoxically, patients had
      significantly higher 2-h radioiodide uptake and 2- to 24-h radioiodide uptake
      ratios compared with heterozygous, unaffected family members, suggesting an
      imbalance between iodide trapping and organification. In transfected COS-7 cells,
      the mutant TSHR had normal surface expression, basal activity, and TSH-binding
      affinity, equally (2.2-fold) increased EC50 values for TSH-induced cAMP and IP
      accumulation, and normal maximum cAMP generation. In contrast, the efficacy of
      TSH for generating IP was more than 7-fold lower with the mutant compared with
      wild-type TSHR. CONCLUSIONS: We identified and characterized a TSHR defect,
      preferentially affecting the IP pathway, with a phenotype distinct from
      previously reported loss-of-function mutations. Results provide the first in vivo
      evidence for the physiological role of the TSHR/IP/Ca2+ cascade in regulating
      iodination. According to systematic in vitro mutagenesis studies, other TSHR
      mutations can result in even complete loss of IP signaling with retained cAMP
      induction. We hypothesize that such TSHR mutations could be the cause in
      unexplained partial organification defects.

PMID- 17456568
TI  - Reduced serum testosterone levels in infant boys conceived by intracytoplasmic
      sperm injection.
AB  - CONTEXT: Concern has been raised for the health of the offspring conceived by
      assisted reproduction technologies. Basal reproductive hormones around 3 months
      of age reflect the pituitary-testicular axis, which is transiently active at this
      age. OBJECTIVES: We tested the hypothesis that transmission of impaired
      testicular function from father to son could be detected at 3 months of age in
      boys conceived by intracytoplasmic sperm injection (ICSI), which is predominantly
      used in the management of male infertility. DESIGN: We conducted a longitudinal
      prospective cohort study, including 125 boys conceived by ICSI, 124 boys
      conceived by in vitro fertilization (IVF), and 933 naturally conceived (NC) boys.
      INTERVENTION: Anthropometrical measurements were performed at birth and at 3
      months of age; 58, 67, and 64% of ICSI, IVF, and NC boys, respectively, had a
      blood sample taken at 3 months. MAIN OUTCOME MEASURES: We measured serum levels
      of LH, FSH, SHBG, inhibin B, testosterone, as well as penile length. RESULTS:
      Serum testosterone levels were significantly lower in boys conceived by ICSI (2.4
      nmol/liter; 0.2-4.9 nmol/liter) (median; 2.5th-97.5th percentiles) compared with
      NC boys (3.3 nmol/liter; 0.6-7.6 nmol/liter; P < 0.001), and the LH to
      testosterone ratio was increased (0.8; 0.2-7.9 vs. 0.5; 0.2-2.3, respectively; P
      = 0.001). Boys conceived by IVF because of female infertility factors had a
      normal serum testosterone and LH to testosterone ratio compared with controls.
      Adjusted analyses for confounders did not alter the results. CONCLUSIONS: Our
      results point toward a subtle impairment of Leydig cell function in boys
      conceived by ICSI, possibly inherited from their fathers. The clinical
      significance of our findings is uncertain. However, our findings should raise
      concern because ICSI is increasingly used to overcome male infertility.

PMID- 17456569
TI  - Growth hormone reduces inflammation in postmenopausal women with abdominal
      obesity: a 12-month, randomized, placebo-controlled trial.
AB  - CONTEXT: Abdominal obesity is associated with low GH secretion, elevated
      circulating markers of inflammation, and increased risk of cardiovascular
      disease. OBJECTIVE: The objective was to study the effect of GH treatment on
      inflammatory markers and vascular adhesion molecules in postmenopausal women with
      abdominal obesity. DESIGN: Forty women aged 51-63 yr received GH (0.67 mg/d) in a
      randomized, double-blind, placebo-controlled, 12-month trial. Measurements of
      inflammatory markers [highly sensitive C-reactive protein (CRP), IL-6, and
      amyloid polypeptideA] and markers of endothelial dysfunction (soluble E-selectin,
      vascular adhesion molecule-1, intercellular molecule-1, and matrix
      metalloproteinase-9) were performed at baseline and after 6 and 12 months of
      treatment. RESULTS: After 12 months, the mean IGF sd score was 0.9 +/- 1.5 and 
      0.8 +/- 0.6 in the GH and placebo groups, respectively. GH treatment reduced CRP
      and IL-6 levels compared with placebo (P = 0.03 and P = 0.05, respectively),
      whereas the markers of endothelial dysfunction were unaffected. Within the GH
      treated group, a reduction was shown in CRP (4.3 +/- 4 to 3.0 +/- 3 mg/liter; P <
      0.05) and in IL-6 (4.4 +/- 2 to 3.3 +/- 2 ng/liter; P < 0.01). In the GH-treated
      group, the decrease in CRP and IL-6 correlated with a reduction in visceral
      adipose tissue (r = 0.7, P < 0.001 and r = 0.5, P < 0.05, respectively).
      CONCLUSION: GH treatment in postmenopausal women with abdominal obesity reduced
      serum markers of systemic inflammation. Circulating markers of endothelial
      dysfunction were unaffected by treatment.

PMID- 17456570
TI  - Serum estrogen, but not testosterone, levels differ between black and white men
      in a nationally representative sample of Americans.
AB  - CONTEXT: Higher testosterone in black compared with white men has been postulated
      to explain their higher prostate cancer incidence. Previous studies comparing
      hormone levels by race might have been limited by size, restricted age variation,
      or lack of representation of the general population. OBJECTIVE: Our objective was
      to compare serum testosterone, estradiol, and SHBG concentrations among non
      Hispanic black, non-Hispanic white, and Mexican-American men. PARTICIPANTS,
      DESIGN, AND SETTING: A total of 1413 men aged 20+ yr and who attended the morning
      examination session of the Third National Health and Nutrition Examination Survey
      (NHANES III) in 1988-1991 were included in this cross-sectional study.
      MEASUREMENT: Serum hormone concentrations were measured by
      electrochemiluminescence immunoassays. RESULTS: After applying sampling weights
      and adjusting for age, percent body fat, alcohol, smoking, and activity,
      testosterone concentrations were not different between non-Hispanic blacks (n =
      363; geometric mean, 5.29 ng/ml) and non-Hispanic whites (n = 674; 5.11 ng/ml; P
      > 0.05) but were higher in Mexican-Americans (n = 376; 5.48 ng/ml; P < 0.05). Non
      Hispanic blacks (40.80 pg/ml) had a higher estradiol concentration than non
      Hispanic whites (35.46 pg/ml; P < 0.01) and Mexican-Americans (34.11 pg/ml; P <
      0.01). Non-Hispanic blacks (36.49 nmol/liter) had a higher SHBG concentration
      than non-Hispanic whites (34.91 nmol/liter; P < 0.05) and Mexican-Americans
      (35.04 nmol/liter; P < 0.05). CONCLUSIONS: Contrary to the postulated racial
      difference, testosterone concentrations did not differ notably between black and
      white men. However, blacks had higher estradiol levels. Mexican-Americans had
      higher testosterone than whites but similar estradiol and SHBG concentrations.
      Given these findings, it may be equally if not more important to investigate
      estradiol as testosterone in relation to diseases with racial disparity.

PMID- 17456571
TI  - Dopamine agonist cabergoline reduces hemoconcentration and ascites in
      hyperstimulated women undergoing assisted reproduction.
AB  - CONTEXT: Ovarian hyperstimulation syndrome (OHSS) results from increased vascular
      permeability (VP) caused by ovarian hypersecretion of vascular endothelial growth
      factor (VEGF), which activates its receptor-2. In animals, the dopamine receptor
      2 agonist cabergoline (Cb2) inactivates VEGF receptor-2 and prevents increased
      VP. OBJECTIVE: Our objective was to test whether Cb2 reduces VP and prevents OHSS
      in humans. DESIGN: We conducted a prospective, randomized, double-blind study on
      oocyte donors at risk of developing OHSS (>20 follicles, >12 mm developed, and
      >20 oocytes retrieved). INTERVENTIONS: Cb2 0.5 mg/d (n = 37) or a placebo (n =
      32) was administered from the day of human chorionic gonadotropin (d 0) until d
      8. Ascites (a pocket of peritoneal fluid > 9 cm(2) in lithotomy position),
      hemoconcentration, and serum prolactin were recorded. Pharmacokinetic studies
      with magnetic resonance employing the transfer constant rate (K(trans), measure
      of permeability) and the extravascular extracellular space (upsilon(e), marker of
      cellular leakage) were performed to measure VP objectively. RESULTS: Hematocrit
      (P < 0.01), hemoglobin (P = 0.003), and ascites (P = 0.005) were significantly
      lower on d 4 and 6 after treatment with Cb2 as compared with placebo. The
      incidence of moderate OHSS was 20.0 and 43.8%, respectively (P = 0.04). Magnetic
      resonance studies showed an increase in VP and extravascular leakage of fluid 5 d
      after human chorionic gonadotropin injection that was significantly prevented
      with Cb2 (K(trans) P = 0.04 and upsilon(e) P = 0.001, respectively). CONCLUSIONS:
      Given that Cb2 is a well-established and safe medication, this study provides
      proof of concept for the use of dopamine agonists in the prevention of OHSS in
      women undergoing assisted reproduction.

PMID- 17456572
TI  - Dissociation between adipose nitric oxide synthase expression and tissue
      metabolism.
AB  - CONTEXT: Nitric oxide synthase (NOS) expression in adipose tissue is increased in
      obese subjects. The functional relevance is not known. OBJECTIVE: The objective
      was to compare adipose tissue metabolism between obese men with greater or lower
      adipose endothelial NOS (eNOS) or inducible NOS (iNOS) expression. DESIGN: The
      design was an open-labeled prospective study. SETTING: The study took place at an
      academic clinical research center. PATIENTS: The patients included 14 obese (32
      +/- 0.6 kg/m2) and eight normal-weight (23 +/- 2 kg/m2) healthy men.
      INTERVENTION: Microdialysis catheters in abdominal sc adipose tissue and in
      vastus lateralis were perfused with N-omega-nitro-L-arginine methyl ester (L
      NAME) or N-omega-nitro-D-arginine methyl ester (D-NAME). Then, incremental
      isoproterenol concentrations were added to the perfusate. MAIN OUTCOME MEASURES:
      Microdialysate glycerol was the main outcome measure. RESULTS: Tissue perfusion
      and microdialysate glycerol concentrations at baseline and during isoproterenol
      stimulation were similar in obese men with high or low eNOS or iNOS expression
      during both L-NAME and D-NAME. During D-NAME, basal and maximal isoproterenol
      stimulated glycerol were similar in lean and in obese men. However, in lean men,
      the dose-response relationship between isoproterenol and glycerol was shifted
      towards the left (P < 0.0001). NOS inhibition with L-NAME had no effect on basal
      or isoproterenol-stimulated glycerol in the obese group in skeletal muscle or in
      adipose tissue. In contrast, L-NAME augmented the lipolytic response in lean
      subjects in both tissues. CONCLUSIONS: Differences in eNOS and iNOS mRNA
      expression at the adipose tissue level may have a limited effect on lipolysis and
      tissue perfusion. The lower resting lipolysis in adipose tissue of obese compared
      with nonobese subjects cannot be explained by a tonic nitric oxide effect.

PMID- 17456573
TI  - Raised serum, adipocyte, and adipose tissue retinol-binding protein 4 in
      overweight women with polycystic ovary syndrome: effects of gonadal and adrenal
      steroids.
AB  - CONTEXT: Polycystic ovary syndrome (PCOS) is associated with insulin resistance
      and obesity. Recent studies have shown that serum retinol-binding protein 4
      (RBP4) levels increase with obesity. Currently, no data exist on the relative
      expression of RBP4 in either serum or adipose tissue of PCOS women. OBJECTIVES:
      mRNA expression of RBP4 from sc and omental (om) adipose tissue and sc adipocytes
      in overweight PCOS women were compared with matched controls; RBP4 protein in
      adipose tissue and serum RBP4 levels were also assessed. Additionally, we studied
      the effects of testosterone, 17beta-estradiol, androstenedione, and
      dehydroepiandrosterone sulfate on RBP4 expression in adipose tissue explants.
      DESIGN: Real-time RT-PCR and Western blotting were used to assess the relative
      mRNA and protein expression of RBP4. Biochemical measurements were also
      performed. RESULTS: Compared with controls, there was significant up-regulation
      of RBP4 mRNA in sc (P < 0.05) and om (P < 0.01) adipose tissue as well as
      isolated sc adipocytes (P < 0.01) of PCOS women. In addition to elevated serum
      RBP4 levels in PCOS women (P < 0.05), RBP4 protein levels were significantly
      greater in sc and om adipose tissue of PCOS women (P < 0.05 and P < 0.05,
      respectively). Furthermore, in human sc and om adipose tissue explants, 17beta
      estradiol significantly increased RBP4 mRNA expression, protein levels, and
      secretion into the culture media (P < 0.05). CONCLUSIONS: The precise reason for
      elevated levels of RBP4 in overweight PCOS women is unknown, but it appears that
      17beta-estradiol may play a role in their regulation in adipose tissue.

PMID- 17456574
TI  - Newborn screening for congenital adrenal hyperplasia: additional steroid profile
      using liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Neonatal screening programs for congenital adrenal hyperplasia (21
      CAH) using an immunoassay for 17alpha-hydroxyprogesterone (17-OHP) generate a
      high rate of positive results attributable to physiological reasons and to cross
      reactions with steroids other than 17alpha-OHP, especially in preterm neonates
      and in critically ill newborns. METHODS: To increase the specificity of the
      screening process, we applied a liquid chromatography-tandem mass spectrometry
      method quantifying 17alpha-OHP, 11-deoxycortisol, 21-deoxycortisol, cortisol, and
      androstenedione. The steroids were eluted in aqueous solution containing d8
      17alpha-OHP and d2-cortisol and quantified in multiple reaction mode. RESULTS:
      Detection limit was below 1 nmol/liter, and recovery ranged from 64%
      (androstenedione) to 83% (cortisol). Linearity was proven within a range of 5-100
      nmol/liter (cortisol, 12.5-200 nmol/liter), and total run time was 6 min.
      Retrospective analysis of 6151 blood samples and 50 blood samples from newborns
      with clinically confirmed 21-CAH, as well as prospective analysis of 1609 samples
      of a total of 242,500 testing positive in our routine 17-OHP immunoassay, allowed
      clear distinction of affected and nonaffected newborns. High levels of 21
      deoxycortisol were only found in children with 21-hydroxylase deficiency.
      Calculating the ratio of 17alpha-OHP to 21-deoxycortisol divided by cortisol
      further increased the sensitivity of the method. CONCLUSION: Our liquid
      chromatography-tandem mass spectrometry procedure as a second-tier test can be
      used to reduce false-positive results of standard 21-CAH screening. The short
      total run time of 6 min allows for immediate reanalysis of all immunoassay
      results above the cutoff.

PMID- 17456575
TI  - Gonadotropin-releasing hormone neurons express estrogen receptor-beta.
AB  - CONTEXT: Recent identification of the second estrogen receptor (ER) isoform (ER
      beta) within GnRH neurons of the rodent brain has generated much enthusiasm in
      the field of neuroendocrine research by questioning the dogma that GnRH cells do
      not directly sense changes in circulating estrogens. OBJECTIVE: To address the
      issue of whether GnRH neurons of the human hypothalamus also contain ER-beta, we
      have performed dual-label immunocytochemical studies. DESIGN: Tissue sections
      were prepared from autopsy samples of male human individuals (n = 8; age < 50
      yr), with sudden causes of death. Technical efforts were made to minimize
      postmortem interval (<24 h), optimize tissue fixation (use of a mixture of 2%
      paraformaldehyde and 4% acrolein for four tissue samples), and sensitize the
      immunocytochemical detection of ER-beta (application of silver-intensified nickel
      diaminobenzidine chromogen). MAIN OUTCOME MEASURE: Distribution and percent ratio
      of GnRH neurons that also contained ER-beta immunoreactivity were analyzed under
      the light microscope. RESULTS: With acrolein in tissue fixative, nuclear ER-beta
      immunoreactivity was observed in 10.8-28.0% of GnRH neurons of the four different
      individuals. ER-beta-containing GnRH neurons were widely distributed in the
      hypothalamus, without showing a noticeable preference in regional location.
      CONCLUSIONS: The demonstration of ER-beta and the previous lack of detection of
      ER-alpha in human GnRH cells indicate that estrogens may exert direct actions
      upon GnRH neurons exclusively through ER-beta. In the light of differing ligand
      binding characteristics of ER-beta from those of ER-alpha, this discovery offers
      a potential new approach to influence estrogen feedback to GnRH neurons through
      ER-beta-selective receptor ligands.

PMID- 17456576
TI  - Monocyte chemoattractant protein-1 in subcutaneous abdominal adipose tissue:
      characterization of interstitial concentration and regulation of gene expression
      by insulin.
AB  - CONTEXT: The chemokine monocyte chemoattractant protein-1 (MCP-1) is implicated
      in obesity-associated chronic inflammation, insulin resistance, and
      atherosclerosis. OBJECTIVES: The objectives of this study were to: 1)
      characterize the interstitial levels and the gene expression of MCP-1 in the sc
      abdominal adipose tissue (SCAAT), 2) elucidate the response of MCP-1 to acute
      hyperinsulinemia, and 3) determine the relationship between MCP-1 and arterial
      stiffness. DESIGN: Nine lean (L) and nine uncomplicated obese (OB) males were
      studied in the fasting state and during a euglycemic-hyperinsulinemic clamp
      combined with the microdialysis technique. Interstitial and serum MCP-1 (iMCP-1
      and sMCP-1, respectively) levels, pulse wave analysis, and SCAAT biopsies were
      characterized at baseline and after hyperinsulinemia. RESULTS: OB showed elevated
      sMCP-1 (P < 0.01) but similar iMCP-1 levels as compared with L. Basal iMCP-1
      concentrations were considerably higher than sMCP-1 (P < 0.0001), and a gradient
      between iMCP-1 and sMCP-1 levels was maintained throughout the hyperinsulinemia.
      At baseline, SCAAT gene expression profile revealed a "co-upregulation" of MCP-1,
      MCP-2, macrophage inflammatory protein-1alpha, and CD68 in OB, and whole-body
      glucose disposal inversely correlated with the MCP-1 gene expression. After
      hyperinsulinemia, MCP-1 and MCP-2 mRNA levels significantly increased in L, but
      not in OB. Finally, sMCP-1 excess in the OB positively correlated with the
      stiffer vasculature. CONCLUSIONS: These observations demonstrate similar
      interstitial concentrations and a differential gene response to hyperinsulinemia
      of MCP-1 in the SCAAT from L and OB individuals. In human obesity, we suggest the
      SCAAT MCP-1 gene overexpression as a biomarker of an "inflamed" adipose organ and
      impaired glucose metabolism.

PMID- 17456577
TI  - High radiosensitivity of germ cells in human male fetus.
AB  - CONTEXT: Germ cells formed during human fetal life are essential for fertility of
      the adult, and 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. However, factors inducing
      a genotoxic stress may also be implicated. OBJECTIVES: We investigated the effect
      of gamma-irradiation on the functions of human fetal testis during the first
      trimester of gestation by using an organ culture system. Then we focused on the
      role of the p53 pathway in the observed effects. RESULTS: Germ cells were highly
      sensitive to irradiation even at doses as low as 0.1 and 0.2 Gy. Indeed, for
      these doses, one third of germ cells died by apoptosis. Other germ cells were
      blocked in their cycle, but no repair seemed to occur, and longer culture with
      the highest dose used showed that they were destined to die. Sertoli cells were
      less affected, although their proliferation and the level of anti-Mullerian
      hormone were reduced. Irradiation had no effect on testosterone secretion or on
      the expression of steroidogenic enzymes by Leydig cells. After irradiation, p53
      phosphorylated on serine 15 was detected from 1-24 h in all cell types. This
      activation of p53 was accompanied by an increase in mRNA levels of proapoptotic
      factors Bax and Puma, whereas that of antiapoptotic Bcl-2 remained unchanged.
      P21, which is responsible for cell cycle arrest, was also up-regulated 6, 30, and
      72 h after irradiation. Finally, when we added pifithrin-alpha, a specific
      inhibitor of p53 functions, a significant decrease in irradiation-induced
      apoptosis in both germ and Sertoli cells was observed, indicating the involvement
      of the p53 pathway in irradiation-induced apoptosis. CONCLUSIONS: This study
      demonstrated here for the first time the great sensitivity of human fetal germ
      cells to genotoxic stress caused by ionizing radiation.

PMID- 17456578
TI  - Increased acute myocardial infarction rates and cardiovascular risk factors among
      patients with human immunodeficiency virus disease.
AB  - CONTEXT: Metabolic changes and smoking are common among HIV patients and may
      confer increased cardiovascular risk. OBJECTIVE: The aim of the study was to
      determine acute myocardial infarction (AMI) rates and cardiovascular risk factors
      in HIV compared with non-HIV patients in two tertiary care hospitals. DESIGN,
      SETTING, AND PARTICIPANTS: We conducted a health care system-based cohort study
      using a large data registry with 3,851 HIV and 1,044,589 non-HIV patients. AMI
      rates were determined among patients receiving longitudinal care between October
      1, 1996, and June 30, 2004. MAIN OUTCOME MEASURES: The primary outcome was
      myocardial infarction, identified by International Classification of Diseases
      coding criteria. RESULTS: AMI was identified in 189 HIV and 26,142 non-HIV
      patients. AMI rates per 1000 person-years were increased in HIV vs. non-HIV
      patients [11.13 (95% confidence interval [CI] 9.58-12.68) vs. 6.98 (95% CI 6.89
      7.06)]. The HIV cohort had significantly higher proportions of hypertension (21.2
      vs. 15.9%), diabetes (11.5 vs. 6.6%), and dyslipidemia (23.3 vs. 17.6%) than the
      non-HIV cohort (P < 0.0001 for each comparison). The difference in AMI rates
      between HIV and non-HIV patients was significant, with a relative risk (RR) of
      1.75 (95% CI 1.51-2.02; P < 0.0001), adjusting for age, gender, race,
      hypertension, diabetes, and dyslipidemia. In gender-stratified models, the
      unadjusted AMI rates per 1000 person-years were higher for HIV patients among
      women (12.71 vs. 4.88 for HIV compared with non-HIV women), but not among men
      (10.48 vs. 11.44 for HIV compared with non-HIV men). The RRs (for HIV vs. non
      HIV) were 2.98 (95% CI 2.33-3.75; P < 0.0001) for women and 1.40 (95% CI 1.16
      1.67; P = 0.0003) for men, adjusting for age, gender, race, hypertension,
      diabetes, and dyslipidemia. A limitation of this database is that it contains
      incomplete data on smoking. Smoking could not be included in the overall
      regression model, and some of the increased risk may be accounted for by
      differences in smoking rates. CONCLUSIONS: AMI rates and cardiovascular risk
      factors were increased in HIV compared with non-HIV patients, particularly among
      women. Cardiac risk modification strategies are important for the long-term care
      of HIV patients.

PMID- 17456580
TI  - A simple theoretical model for the air flow and particle penetration in a
      modified horizontal elutriator with plates of unequal lengths.
AB  - A simple theoretical model is presented for the distribution of air speeds in a
      modified horizontal elutriator consisting of groups of plates with different
      lengths. Equations are presented for calculating the particle penetration both in
      channels of shortended plate lengths, as downstream the end of a shortended
      plate.

PMID- 17456579
TI  - Development, evaluation and data acquired with a tape-stripping technique for
      measuring dermal exposure to budesonide at a pharmaceutical manufacturing site.
AB  - OBJECTIVES: Although corticosteroids have been used for over 50 years as anti
      inflammatory and anti-proliferative agents, few studies have examined their
      exposure levels and health effects on workers employed in the corticosteroid
      manufacturing industry. The aims of the study reported here were to develop a
      tape-stripping technique for monitoring budesonide (a corticosteroid used in
      inhalators for treating respiratory diseases) and to apply the method in a pilot
      study to estimate the potential dermal exposure to budesonide among workers at a
      pharmaceutical formulation site. METHODS: The tape-stripping method was evaluated
      by applying 0.5 and 2.07 microg of budesonide dissolved in ethanol on tape
      strips. The same amounts were also applied on a cleaned glass plate and human
      skin of volunteers, which were then stripped by series of tapes immediately, and
      30 min later, the amounts collected by the tapes were measured. Finally, the
      technique was used to study the exposure of budesonide among eight employees at a
      pharmaceutical industry site. Three exposure sites were tested: the tip of the
      forefinger, palm of the hand and ventral part of the lower arm. Five consecutive
      tape strips per sampling site were used in both the recovery studies and the
      field study. RESULTS: The mean overall recoveries from spiked tapes and the glass
      plate were 96 and 81%, respectively, while for human skin the corresponding
      figure was 38%, (for applications of 2.07 microg; no detectable amounts were
      recovered from human skin after 0.5 microg applications). The recovered amount
      was found on two consecutive tapes after 0 min, but only on the first tape strip
      after 30 min. The inter-individual variability was 4-fold. In the field,
      quantifiable amounts were found for four of eight employees and a concentration
      gradient was detected along the two or three consecutive tape strips. The tip of
      the forefinger and the palm of the hand were the most highly exposed sites to
      budesonide. CONCLUSIONS: A tape-stripping method can be used to determine
      potential dermal exposure to budesonide. The results also indicate that
      budesonide is taken up by the skin of operators who are exposed to the substance
      at their workplace.

PMID- 17456581
TI  - Measurement of asbestos fibre concentrations in fluid of repeated bro-choalveolar
      lavages of exposed workers.
AB  - OBJECTIVES: The aim of this study was to assess the reliability of asbestos fibre
      concentration in bronchoalveolar lavage fluid (BALF) by carrying out the
      mineralogical analysis of BALF at different times in the same patient and
      comparing the results. METHODS: Twenty two patients underwent diagnostic
      fibreoptic bronchoscopy twice: the first was to assess the past asbestos exposure
      and the second for different clinical reasons. Mineralogical analysis of BALF was
      carried out. RESULTS: In 16 patients (72.7%), a reduction of concentration in
      BALF of all asbestos fibres was observed. The concentrations of both chrysotile
      and amphiboles in the first bronchoalveolar lavage (BAL) were related to their
      concentrations in the second BAL and the observed differences were not
      statistically significant. A significant decrease in asbestos body concentration
      between the first and the second BAL was found (Wilcoxon test, P < 0.01).
      CONCLUSIONS: The reliability of the fibre concentration in BALF as a marker of
      past asbestos exposure seems quite good. In most cases, it allows us to
      distinguish workers in different classes of exposure and gives useful information
      on the pattern of exposure. Uncertainties related in general to lung residues and
      in particular to mineralogical analysis of BALF (mainly due to the high
      coefficient of variation (CV) at low fibre concentrations and the results of the
      statistical analysis on total fibres) suggest that this biomarker is more likely
      suitable for a qualitative/categorical approach to exposure assessment than a
      quantitative one.

PMID- 17456582
TI  - Redesign of a static horizontal elutriator to perform according to the ISO 7708
      respirable convention.
AB  - A static horizontal elutriator (multi-channel elutriator C-30, Sibata Scientific
      Instruments Ltd, Tokyo) has been widely used as a dust size classifier for a low
      volume air sampler in Japan. The sampler uses the historical criterion defined by
      the British Medical Research Council (BMRC). However, a new sampling convention
      based on the ISO 7708 respirable dust convention was recently introduced into the
      Japanese standard for work environment measurement. It is necessary to modify the
      multi-channel static horizontal elutriator to satisfy the ISO 7708 respirable
      convention. We propose a modification of the horizontal elutriator, involving the
      shortening of 11 of the 36 plates to meet the ISO 7708 respirable convention. The
      relationship between aerosol particle size and penetration for the elutriator was
      measured in calm air. The measured penetrations were compared with the calculated
      performance of the sampler and with the sampling convention for the ISO
      respirable dust. The calculated bias of sampled masses with respect to the ISO
      respirable mass was almost zero for the workplace aerosols.

PMID- 17456583
TI  - Similarity in pharmacokinetics of oseltamivir and oseltamivir carboxylate in
      Japanese and Caucasian subjects.
AB  - The pharmacokinetics of oseltamivir and oseltamivir carboxylate in healthy
      Japanese (n = 14) and Caucasian (n = 14) males were compared. Subjects in each
      ethnic group were randomized to twice-daily oral oseltamivir 75 mg, 150 mg, or
      placebo for 13 doses. Oseltamivir was well tolerated across doses and ethnic
      groups. Oseltamivir was rapidly absorbed and hydrolyzed to oseltamivir
      carboxylate in all subjects. The mean plasma concentration-time profiles for
      oseltamivir and oseltamivir carboxylate were similar in Japanese and Caucasian
      subjects. At steady state, there was no evidence of any ethnic difference in the
      individual AUC(0-12) values for oseltamivir or oseltamivir carboxylate. Despite a
      significant difference in group mean body weight (approximately 20 kg) between
      the Japanese and Caucasian subjects, there was no evidence that dose-adjusted
      AUC(0-12) and C(max) for oseltamivir carboxylate were affected by body weight or
      ethnicity. Day 7 trough concentrations (C(min)) for oseltamivir carboxylate
      markedly exceeded the IC(50) (50% inhibitory concentration) against influenza A
      and B isolates. In conclusion, the results of this study support the use of the
      same dose regimens of oseltamivir in both Caucasian and Japanese subjects because
      of similarity in pharmacokinetics.

PMID- 17456584
TI  - The SIL gene is essential for mitotic entry and survival of cancer cells.
AB  - Although mitosis is a general physiologic process, cancer cells are unusually
      sensitive to mitotic inhibitors. Therefore, there is an interest in the
      identification of novel mitotic inhibitors. Here, we report the novel discovery
      of the SIL gene as a regulator of mitotic entry and cell survival. The SIL gene
      was cloned from leukemia-associated chromosomal translocation. It encodes a
      cytosolic protein with an unknown function and no homology to known proteins.
      Previously, we observed an increased expression of SIL in multiple cancers that
      correlated with the expression of mitotic spindle checkpoint genes and with
      increased metastatic potential. Here, we show that SIL is important for the
      transition from the G(2) to the M phases of the cell cycle. Inducible knockdown
      of SIL in cancer cells in vitro delayed entrance into mitosis, decreased
      activation of the CDK1 (CDC2)-cyclin B complex, and induced apoptosis in a p53
      independent manner. SIL is also essential for the growth of tumor explants in
      mice. Thus, SIL is required for mitotic entry and cancer cell survival. Because
      increased expression of SIL has been noted in multiple types of cancers and
      correlates with metastatic spread, it may be a suitable target for novel
      anticancer therapy.

PMID- 17456585
TI  - LOXL1 and LOXL4 are epigenetically silenced and can inhibit ras/extracellular
      signal-regulated kinase signaling pathway in human bladder cancer.
AB  - Promoter hypermethylation is one of the common mechanisms leading to gene
      silencing in various human cancers. Using a combination of pharmacologic
      unmasking and microarray techniques, we identified 59 candidate hypermethylated
      genes, including LOXL1, a lysyl oxidase-like gene, in human bladder cancer cells.
      We further showed that LOXL1 and LOXL4 are commonly silenced genes in human
      bladder cancer cells, and this silence is predominantly related to promoter
      methylation. We also found LOXL1 and LOXL4 gene methylation and loss of
      expression in primary bladder tumors. In addition, somatic mutations were
      identified in LOXL4, but not in LOXL1 in bladder cancer. Moreover, reintroduction
      of LOXL1 and LOXL4 genes into human bladder cancer cells leads to a decrease of
      colony formation ability. Further studies indicated that the overexpression of
      LOXL1 and LOXL4 could antagonize Ras in activating the extracellular signal
      regulated kinase (ERK) signaling pathway. Thus, our current study suggests for
      the first time that lysyl oxidase-like genes can act as tumor suppressor genes
      and exert their functions through the inhibition of the Ras/ERK signaling pathway
      in human bladder cancer.

PMID- 17456586
TI  - Respiratory periodicity and electroencephalogram arousals during sleep in older
      adults.
AB  - The aim of this exploratory study was to examine the relationship of
      electroencephalogram (EEG) arousals to breathing patterns and the relationship of
      both arousals and breathing patterns to arterial oxygenation during sleep in
      older adults. Five older adults were monitored using standard polysomnography.
      Records were divided into 5-min segments and breathing patterns identified based
      on the level of respiratory periodicity and the variability in the frequency of
      breathing cycles. Standard criteria were used to determine sleep states and
      occurrence of EEG arousals. High respiratory periodicity was seen in 23% of the
      segments, whereas 24% had low respiratory periodicity with minimal variability in
      the frequency of breathing (Type A low respiratory periodicity) and 53% had low
      respiratory periodicity with high variability in the frequency of breathing (Type
      B low respiratory periodicity). Nearly all (97%) segments with high respiratory
      periodicity had EEG arousals, whereas fewer segments (33%) with low respiratory
      periodicity had arousals, regardless of the stage of sleep. Desaturations
      occurred more often in segments with high respiratory periodicity, F((2,4)) =
      57.3, p < .001, but overall, the mean SaO(2) of segments with high respiratory
      periodicity did not differ from levels seen in segments with low respiratory
      periodicity, F((2,4)) = 0.77, ns. Our findings suggest that high respiratory
      periodicity is a common feature of EEG arousals and, in older adults, may be
      important for maintaining oxygen levels during desaturations during sleep.

PMID- 17456587
TI  - Cytokines in chronically critically ill patients after activity and rest.
AB  - Inflammation, a common problem for patients in the intensive care unit (ICU),
      frequently is associated with serious and prolonged critical illnesses. To date,
      no study has examined whether physical activity influences inflammatory factors
      in critically ill adults. The objectives of this study were to (a) examine the
      relationships between type and duration of physical activity and serum levels of
      interleukin 6 (IL-6), a proinflammatory cytokine; IL-10, an anti-inflammatory
      cytokine; and their ratio and (b) determine if there are associations between
      cytokines or their ratio and activity or outcomes. This descriptive feasibility
      study investigated the approaches to measuring levels of physical activity and
      its relationship to serum levels of IL-6 and IL-10 and the ratio between them in
      patients with prolonged mechanical ventilation during periods of activity and
      rest. Measurements included serum IL-6 and IL-10 levels, direct observation and
      actigraphy, and prospective chart review. Ten critically ill patients who were
      mechanically ventilated for an average of 10 days in a large, urban, teaching
      hospital were enrolled. The average ratio of IL-6 to IL-10 improved after an
      average of 14.7 min of passive physical activity, typically multiple in-bed turns
      associated with hygiene. IL-6, IL-10, and their ratio were not associated with
      patient outcomes of weaning success or length of stay. High levels of IL-6 were
      associated with mortality. Cytokine balance may be improved by low levels of
      activity among patients with prolonged critical illness. The pattern of cytokines
      produced after activity may improve patients' recovery from prolonged critical
      illness and mechanical ventilation.

PMID- 17456588
TI  - Fetal development: voice processing in normotensive and hypertensive pregnancies.
AB  - Recent observation of maternal voice recognition provides evidence of rudimentary
      memory and learning in healthy term fetuses. However, such higher order auditory
      processing has not been examined in the presence of maternal hypertension, which
      is associated with reduced and/or impaired uteroplacental blood flow. In this
      study, voice processing was examined in 40 fetuses (gestational ages of 33 to 41
      weeks) of hypertensive and normotensive women. Fetuses received 2 min of no
      sound, 2 min of a tape-recorded story read by their mothers or by a female
      stranger, and 2 min of no sound while fetal heart rate was recorded. Results
      demonstrated that fetuses in the normotensive group had heart rate accelerations
      during the playing of their mother's voice, whereas the response occurred in the
      hypertensive group following maternal voice offset. Across all fetuses, a greater
      fetal heart rate change was observed when the amniotic fluid index was above
      compared to below the median (i.e., 150 mm), indicating that amniotic fluid
      volume may be an independent moderator of fetal auditory sensitivity. It was
      concluded that differential fetal responding to the mother's voice in pregnancies
      complicated by maternal hypertension may reflect functional elevation of
      sensorineural threshold or a delay in auditory system maturation, signifying
      functional differences during fetal life or subtle differences in the development
      of the central nervous system.

PMID- 17456589
TI  - Heart rate variability in premature infants during feeding.
AB  - Early mother-infant interaction, a potentially major contributor to the
      development of a premature infant's behavioral and physiologic regulation, has
      received very little research attention. This study examined the development of
      physiologic regulation in relation to maternal-infant feeding interaction for 43
      premature infants, from the time caregiving responsibility was transferred to the
      mother through each infant's 4th postterm month. Infants and mothers were seen in
      a special care nursery just before discharge and in home at 1 and 4 months
      postterm age. General linear mixed models were used to examine the changes in
      infant heart rate variability (HRV) and Positive Affective Involvement and
      Sensitivity/Responsiveness scores over time and infant HRV over feeding
      conditions (prefeeding, feeding, and postfeeding). Significant differences were
      found for high-frequency and low-frequency HRV over time (p < .001 and p = .014,
      respectively). However, maternal feeding behavior did not show a significant
      effect of time (p = .24). The feeding condition effect on high-frequency HRV was
      significant (p < .001), with HRV lower during feeding compared to both prefeeding
      and postfeeding. Maternal feeding behavior was not associated with infant HRV.
      Discovering the ways in which maternal feeding behavior contributes to infant
      physiologic regulation may require study of the relationship of HRV to infant
      feeding behavior.

PMID- 17456590
TI  - The effect of kappa opioid receptor antagonism on energy expenditure in the obese
      Zucker rat.
AB  - Food intake and, subsequently, body weight are influenced by endogenous opioids
      acting in the central nervous system. Agonists for the opioid receptor increase
      food intake, whereas antagonists reduce food intake. Body weight, however, is the
      result of food consumed and energy expended. Although much has been reported
      about the effect of opioid antagonism on food intake, less has been reported
      about its effect on energy expended. This study investigated the effect of
      selective antagonism of the kappa opioid receptor on food intake, body weight,
      and indicators of energy expenditure in male obese Zucker rats (n=10). Energy
      expenditure was measured by indirect calorimetry, whereas general activity and
      body temperature were measured by implanted radio frequency telemetry. Central
      administration of 30 microg of the kappa opioid receptor (KOR) antagonist
      norbinaltorphamine resulted in a significant 34% reduction in food intake (p
      =.001), a small reduction in body weight, a reduction in resting energy
      expenditure (p = .06), a reduction in respiratory quotient (p =.06), a 14%
      reduction in general activity, and a reduction in core body temperature.
      Reduction in body weight as a result of KOR inhibition in this study was related
      to a decrease in food intake but not related to an increase in energy expended or
      activity.

PMID- 17456591
TI  - The dose-dependent effects of chronic iron overload on the production of oxygen
      free radicals and vitamin E concentrations in the liver of a murine model.
AB  - Genetic disorders of iron metabolism such as primary and secondary
      hemochromatosis affect thousands of individuals worldwide and are major causes of
      liver dysfunction, morbidity, and mortality. Although the exact mechanism of
      hepatic injury associated with these genetic disorders is not fully understood,
      the propagation of excess concentrations of iron-catalyzed oxygen free radicals
      (OFRs) may play a role. The authors hypothesized that chronic iron burden would
      result in dose-dependent (a) increases in hepatic iron stores, (b) increases in
      hepatic OFR-mediated hepatic cellular injury as quantified by the cytotoxic
      aldehydes malondialdehyde (MDA) and hexanal, and (c) decreases in protective
      antioxidant reserve status as quantified by plasma vitamin E (alpha-tocopherol)
      levels in a murine model. Twenty B(6)D(2)F1 male mice were randomized to the (a)
      saline control (0.05 mL intraperiotoneal [i.p.]/mouse/day, n = 5), (b) 100 mg
      total iron burden (n = 5), (c) 200 mg total iron burden (n = 5), or (d) 400 mg
      total iron burden (n = 5) group. Iron burden was achieved by daily injections of
      iron dextran (Imferon, 0.05 mL i.p./mouse/day). In comparison to control mice and
      in support of the hypothesis, the authors observed significant dose-dependent
      increases in total hepatic iron burden (p < .001) with corresponding increases in
      MDA and hexanal concentrations (p < .001) and decreases in the protective plasma
      antioxidant vitamin E (p < .001). These findings suggest that iron-catalyzed OFR
      mediated damage may play a role in damaging the liver in chronic states of iron
      burden.

PMID- 17456592
TI  - Methods of measuring insulin sensitivity.
AB  - Insulin resistance is a component of several health disorders, most notably
      impaired glucose tolerance and type 2 diabetes mellitus. Insulin-resistant
      individuals have an impaired biological response to the usual action of insulin;
      that is, they have reduced insulin sensitivity. Various methods are used to
      assess insulin sensitivity both in individuals and in study populations.
      Validity, reproducibility, cost, and degree of subject burden are important
      factors for both clinicians and researchers to consider when weighing the merits
      of a particular method. This article describes several in vivo methods used to
      assess insulin sensitivity and presents the advantages and disadvantages of each.

PMID- 17456593
TI  - In vivo imaging and genetic analysis link bacterial motility and symbiosis in the
      zebrafish gut.
AB  - Complex microbial communities reside within the intestines of humans and other
      vertebrates. Remarkably little is known about how these microbial consortia are
      established in various locations within the gut, how members of these consortia
      behave within their dynamic ecosystems, or what microbial factors mediate
      mutually beneficial host-microbial interactions. Using a gnotobiotic zebrafish
      Pseudomonas aeruginosa model, we show that the transparency of this vertebrate
      species, coupled with methods for raising these animals under germ-free
      conditions can be used to monitor microbial movement and localization within the
      intestine in vivo and in real time. Germ-free zebrafish colonized with isogenic
      P. aeruginosa strains containing deletions of genes related to motility and
      pathogenesis revealed that loss of flagellar function results in attenuation of
      evolutionarily conserved host innate immune responses but not conserved nutrient
      responses. These results demonstrate the utility of gnotobiotic zebrafish in
      defining the behavior and localization of bacteria within the living vertebrate
      gut, identifying bacterial genes that affect these processes, and assessing the
      impact of these genes on host-microbial interactions.

PMID- 17456594
TI  - The macrophage-stimulating protein pathway promotes metastasis in a mouse model
      for breast cancer and predicts poor prognosis in humans.
AB  - A better understanding of tumor metastasis requires development of animal models
      that authentically reproduce the metastatic process. By modifying an existing
      mouse model of breast cancer, we discovered that macrophage-stimulating protein
      promoted breast tumor growth and metastasis to several organs. A special feature
      of our findings was the occurrence of osteolytic bone metastases, which are
      prominent in human breast cancer. To explore the clinical relevance of our model,
      we examined expression levels of three genes involved in activation of the MSP
      signaling pathway (MSP, MT-SP1, and MST1R) in human breast tumors. We found that
      overexpression of MSP, MT-SP1, and MST1R was a strong independent indicator of
      both metastasis and death in human breast cancer patients and significantly
      increased the accuracy of an existing gene expression signature for poor
      prognosis. These data suggest that signaling initiated by MSP is an important
      contributor to metastasis of breast cancer and introduce an independent biomarker
      for assessing the prognosis of humans with breast cancer.

PMID- 17456595
TI  - Discovery of platencin, a dual FabF and FabH inhibitor with in vivo antibiotic
      properties.
AB  - Emergence of bacterial resistance is a major issue for all classes of
      antibiotics; therefore, the identification of new classes is critically needed.
      Recently we reported the discovery of platensimycin by screening natural product
      extracts using a target-based whole-cell strategy with antisense silencing
      technology in concert with cell free biochemical validations. Continued screening
      efforts led to the discovery of platencin, a novel natural product that is
      chemically and biologically related but different from platensimycin. Platencin
      exhibits a broad-spectrum Gram-positive antibacterial activity through inhibition
      of fatty acid biosynthesis. It does not exhibit cross-resistance to key
      antibiotic resistant strains tested, including methicillin-resistant
      Staphylococcus aureus, vancomycin-intermediate S. aureus, and vancomycin
      resistant Enterococci. Platencin shows potent in vivo efficacy without any
      observed toxicity. It targets two essential proteins, beta-ketoacyl-[acyl carrier
      protein (ACP)] synthase II (FabF) and III (FabH) with IC50 values of 1.95 and
      3.91 microg/ml, respectively, whereas platensimycin targets only FabF (IC50 =
      0.13 microg/ml) in S. aureus, emphasizing the fact that more antibiotics with
      novel structures and new modes of action can be discovered by using this
      antisense differential sensitivity whole-cell screening paradigm.

PMID- 17456596
TI  - Bacteriocin production as a mechanism for the antiinfective activity of
      Lactobacillus salivarius UCC118.
AB  - The mechanisms by which probiotic strains enhance the health of the host remain
      largely uncharacterized. Here we demonstrate that Lactobacillus salivarius
      UCC118, a recently sequenced and genetically tractable probiotic strain of human
      origin, produces a bacteriocin in vivo that can significantly protect mice
      against infection with the invasive foodborne pathogen Listeria monocytogenes. A
      stable mutant of Lb. salivarius UCC118 that is unable to produce the Abp118
      bacteriocin also failed to protect mice against infection with two strains of L.
      monocytogenes, EGDe and LO28, confirming that bacteriocin production is the
      primary mediator of protection against this organism. Furthermore, Lb. salivarius
      UCC118 did not offer any protection when mice were infected with a strain of L.
      monocytogenes expressing the cognate Abp118 immunity protein AbpIM, confirming
      that the antimicrobial effect is a result of direct antagonism between Lb.
      salivarius and the pathogen, mediated by the bacteriocin Abp118.

PMID- 17456597
TI  - The structure of a birnavirus polymerase reveals a distinct active site topology.
AB  - Single-subunit polymerases are universally encoded in both cellular organisms and
      viruses. Their three-dimensional structures have the shape of a right-hand with
      the active site located in the palm region, which has a topology similar to that
      of the RNA recognition motif (RRM) found in many RNA-binding proteins.
      Considering that polymerases have well conserved structures, it was surprising
      that the RNA-dependent RNA polymerases from birnaviruses, a group of dsRNA
      viruses, have their catalytic motifs arranged in a permuted order in sequence.
      Here we report the 2.5 A structure of a birnavirus VP1 in which the polymerase
      palm subdomain adopts a new active site topology that has not been previously
      observed in other polymerases. In addition, the polymerase motif C of VP1 has the
      sequence of -ADN-, a highly unusual feature for RNA-dependent polymerases.
      Through site-directed mutagenesis, we have shown that changing the VP1 motif C
      from -ADN- to -GDD- results in a mutant with an increased RNA synthesis activity.
      Our results indicate that the active site topology of VP1 may represent a newly
      developed branch in polymerase evolution, and that birnaviruses may have acquired
      the -ADN- mutation to control their growth rate.

PMID- 17456599
TI  - Following evolution's lead to a single residue switch for diterpene synthase
      product outcome.
AB  - There have been few insights into the biochemical origins of natural product
      biosynthesis from primary metabolism. Of particular interest are terpene
      synthases, which often mediate the committed step in particular biosynthetic
      pathways so that alteration of their product outcome is a key step in the
      derivation of novel natural products. These enzymes also catalyze complex
      reactions of significant mechanistic interest. Following an evolutionary lead
      from two recently diverged, functionally distinct diterpene synthase orthologs
      from different subspecies of rice, we have identified a single residue that can
      switch product outcome. Specifically, the mutation of a conserved isoleucine to
      threonine that acts to convert not only the originally targeted isokaurene
      synthase into a specific pimaradiene synthase but also has a much broader effect,
      which includes conversion of the ent-kaurene synthases found in all higher plants
      for gibberellin phytohormone biosynthesis to the production of pimaradiene. This
      surprisingly facile switch for diterpene synthase catalytic specificity indicates
      the ease with which primary (gibberellin) metabolism can be subverted to
      secondary biosynthesis and may underlie the widespread occurrence of pimaradiene
      derived natural products. In addition, because this isoleucine is required for
      the mechanistically more complex cyclization to tetracyclic kaurene, whereas
      substitution with threonine "short-circuits" this mechanism to produce the
      "simpler" tricyclic pimaradiene, our results have some implications regarding the
      means by which terpene synthases specify product outcome.

PMID- 17456600
TI  - The limited impact of kinship on cooperation in wild chimpanzees.
AB  - The complex cooperative behavior exhibited by wild chimpanzees generates
      considerable theoretical and empirical interest, yet we know very little about
      the mechanisms responsible for its evolution. Here, we investigate the influence
      of kinship on the cooperative behavior of male chimpanzees living in an unusually
      large community at Ngogo in Kibale National Park, Uganda. Using long-term field
      observations and molecular genetic techniques to identify kin relations between
      individuals, we show that male chimpanzees clearly prefer to affiliate and
      cooperate with their maternal brothers in several behavioral contexts. Despite
      these results, additional analyses reveal that the impact of kinship is limited;
      paternal brothers do not selectively affiliate and cooperate, probably because
      they cannot be reliably recognized, and the majority of highly affiliative and
      cooperative dyads are actually unrelated or distantly related. These findings add
      to a growing body of research that indicates that animals cooperate with each
      other to obtain both direct and indirect fitness benefits and that complex
      cooperation can occur between kin and nonkin alike.

PMID- 17456598
TI  - Distinct functional motifs within the IL-17 receptor regulate signal transduction
      and target gene expression.
AB  - IL-17 is the founding member of a novel family of proinflammatory cytokines that
      defines a new class of CD4+ effector T cells, termed "Th17." Mounting evidence
      suggests that IL-17 and Th17 cells cause pathology in autoimmunity, but little is
      known about mechanisms of IL-17RA signaling. IL-17 through its receptor (IL-17RA)
      activates genes typical of innate immune cytokines, such as TNFalpha and IL
      1beta, despite minimal sequence similarity in their respective receptors. A
      previous bioinformatics study predicted a subdomain in IL-17-family receptors
      with homology to a Toll/IL-1R (TIR) domain, termed the "SEFIR domain." However,
      the SEFIR domain lacks motifs critical for bona fide TIR domains, and its
      functionality was never verified. Here, we used a reconstitution system in IL
      17RA-null fibroblasts to map functional domains within IL-17RA. We demonstrate
      that the SEFIR domain mediates IL-17RA signaling independently of classic TIR
      adaptors, such as MyD88 and TRIF. Moreover, we identified a previously
      undescribed"TIR-like loop" (TILL) required for activation of NF-kappaB, MAPK, and
      up-regulation of C/EBPbeta and C/EBPdelta. Mutagenesis of the TILL domain
      revealed a site analogous to the LPS(d) mutation in TLR4, which renders mice
      insensitive to LPS. However, a putative salt bridge typically found in TIR
      domains appears to be dispensable. We further identified a C-terminal domain
      required for activation of C/EBPbeta and induction of a subset IL-17 target
      genes. This structure-function analysis of a IL-17 superfamily receptor reveals
      important differences in IL-17RA compared with IL-1/TLR receptors.

PMID- 17456601
TI  - Stoichiometric controls of mercury dilution by growth.
AB  - Rapid growth could significantly reduce methylmercury (MeHg) concentrations in
      aquatic organisms by causing a greater than proportional gain in biomass relative
      to MeHg (somatic growth dilution). We hypothesized that rapid growth from the
      consumption of high-quality algae, defined by algal nutrient stoichiometry,
      reduces MeHg concentrations in zooplankton, a major source of MeHg for lake fish.
      Using a MeHg radiotracer, we measured changes in MeHg concentrations, growth and
      ingestion rates in juvenile Daphnia pulex fed either high (C:P = 139) or low
      quality (C:P = 1317) algae (Ankistrodesmus falcatus) for 5 d. We estimated
      Daphnia steady-state MeHg concentrations, using a biokinetic model parameterized
      with experimental rates. Daphnia MeHg assimilation efficiencies (approximately
      95%) and release rates (0.04 d(-1)) were unaffected by algal nutrient quality.
      However, Daphnia growth rate was 3.5 times greater when fed high-quality algae,
      resulting in pronounced somatic growth dilution. Steady-state MeHg concentrations
      in Daphnia that consumed high-quality algae were one-third those of Daphnia that
      consumed low-quality algae due to higher growth and slightly lower ingestion
      rates. Our findings show that rapid growth from high-quality food consumption can
      significantly reduce the accumulation and trophic transfer of MeHg in freshwater
      food webs.

PMID- 17456602
TI  - A family of glycosylphosphatidylinositol-linked aspartyl proteases is required
      for virulence of Candida glabrata.
AB  - Candida glabrata is a yeast pathogen of humans. We have established a tissue
      culture model to analyze the interaction of C. glabrata with macrophages.
      Transcript profiling of yeast ingested by macrophages reveals global changes in
      metabolism as well as increased expression of a gene family (YPS genes) encoding
      extracellular glycosylphosphatidylinositol-linked aspartyl proteases. Eight of
      these YPS genes are found in a cluster that is unique to C. glabrata. Genetic
      analysis shows that the C. glabrata YPS genes are required for cell wall
      integrity, adherence to mammalian cells, survival in macrophages and virulence.
      By monitoring the processing of a cell wall adhesin, Epa1, we also show that Yps
      proteases play an important role in cell wall re-modeling by removal and release
      of glycosylphosphatidylinositol-anchored cell wall proteins.

PMID- 17456603
TI  - Human prion proteins with pathogenic mutations share common conformational
      changes resulting in enhanced binding to glycosaminoglycans.
AB  - Mutation in the prion gene PRNP accounts for 10-15% of human prion diseases.
      However, little is known about the mechanisms by which mutant prion proteins
      (PrPs) cause disease. Here we investigated the effects of 10 different pathogenic
      mutations on the conformation and ligand-binding activity of recombinant human
      PrP (rPrP). We found that mutant rPrPs react more strongly with N terminus
      specific antibodies, indicative of a more exposed N terminus. The N terminus of
      PrP contains a glycosaminoglycan (GAG)-binding motif. Binding of GAG is important
      in prion disease. Accordingly, all mutant rPrPs bind more GAG, and GAG promotes
      the aggregation of mutant rPrPs more efficiently than wild-type recombinant
      normal cellular PrP (rPrP(C)). Furthermore, point mutations in PRNP also cause
      conformational changes in the region between residues 109 and 136, resulting in
      the exposure of a second, normally buried, GAG-binding motif. Importantly, brain
      derived PrP from transgenic mice, which express a pathogenic mutant with nine
      extra octapeptide repeats, also binds more strongly to GAG than wild-type PrP(C).
      Thus, several rPrPs with distinct pathogenic mutations have common conformational
      changes, which enhance binding to GAG. These changes may contribute to the
      pathogenesis of inherited prion diseases.

PMID- 17456604
TI  - Frequency and phenotypic implications of mitochondrial DNA mutations in human
      squamous cell cancers of the head and neck.
AB  - Mitochondrial genomic mutations are found in a variety of human cancers; however,
      the frequency of mitochondrial DNA (mtDNA) mutations in coding regions remains
      poorly defined, and the functional effects of mitochondrial mutations found in
      primary human cancers are not well described. Using MitoChip, we sequenced the
      whole mitochondrial genome in 83 head and neck squamous cell carcinomas. Forty
      one of 83 (49%) tumors contained mtDNA mutations. Mutations occurred within
      noncoding (D-loop) and coding regions. A nonrandom distribution of mutations was
      found throughout the mitochondrial enzyme complex components. Sequencing of
      margins with dysplasia demonstrated an identical nonconservative mitochondrial
      mutation (A76T in ND4L) as the tumor, suggesting a role of mtDNA mutation in
      tumor progression. Analysis of p53 status showed that mtDNA mutations correlated
      positively with p53 mutations (P < 0.002). To characterize biological function of
      the mtDNA mutations, we cloned NADH dehydrogenase subunit 2 (ND2) mutants based
      on primary tumor mutations. Expression of the nuclear-transcribed, mitochondrial
      targeted ND2 mutants resulted in increased anchorage-dependent and -independent
      growth, which was accompanied by increased reactive oxygen species production and
      an aerobic glycolytic metabolic phenotype with hypoxia-inducible factor (HIF)
      1alpha induction that is reversible by ascorbate. Cancer-specific mitochondrial
      mutations may contribute to development of a malignant phenotype by direct
      genotoxic effects from increased reactive oxygen species production as well as
      induction of aerobic glycolysis and growth promotion.

PMID- 17456605
TI  - Structure and tie strengths in mobile communication networks.
AB  - Electronic databases, from phone to e-mails logs, currently provide detailed
      records of human communication patterns, offering novel avenues to map and
      explore the structure of social and communication networks. Here we examine the
      communication patterns of millions of mobile phone users, allowing us to
      simultaneously study the local and the global structure of a society-wide
      communication network. We observe a coupling between interaction strengths and
      the network's local structure, with the counterintuitive consequence that social
      networks are robust to the removal of the strong ties but fall apart after a
      phase transition if the weak ties are removed. We show that this coupling
      significantly slows the diffusion process, resulting in dynamic trapping of
      information in communities and find that, when it comes to information diffusion,
      weak and strong ties are both simultaneously ineffective.

PMID- 17456606
TI  - The impact of herbivore-plant coevolution on plant community structure.
AB  - Coevolutionary theory proposes that the diversity of chemical structures found in
      plants is, in large part, the result of selection by herbivores. Because
      herbivores often feed on chemically similar plants, they should impose selective
      pressures on plants to diverge chemically or bias community assembly toward
      chemical divergence. Using a coevolved interaction between a group of chrysomelid
      beetles and their host plants, I tested whether coexisting plants of the Mexican
      tropical dry forest tend to be chemically more dissimilar than random. Results
      show that some of the communities are chemically overdispersed and that
      overdispersion is related to the tightness of the interaction between plants and
      herbivores and the spatial scale at which communities are measured. As
      coevolutionary specialization increases and spatial scale decreases, communities
      tend to be more chemically dissimilar. At fairly local scales and where
      herbivores have tight, one-to-one interactions with plants, communities have a
      strong pattern of chemical disparity.

PMID- 17456607
TI  - The coordination chemistry of saturated molecules.

PMID- 17456608
TI  - Functional evaluation of domain-domain interactions and human protein interaction
      networks.
AB  - MOTIVATION: Large amounts of protein and domain interaction data are being
      produced by experimental high-throughput techniques and computational approaches.
      To gain insight into the value of the provided data, we used our new similarity
      measure based on the Gene Ontology (GO) to evaluate the molecular functions and
      biological processes of interacting proteins or domains. The applied measure
      particularly addresses the frequent annotation of proteins or domains with
      multiple GO terms. RESULTS: Using our similarity measure, we compare predicted
      domain-domain and human protein-protein interactions with experimentally derived
      interactions. The results show that our similarity measure is of significant
      benefit in quality assessment and confidence ranking of domain and protein
      networks. We also derive useful confidence score thresholds for dividing domain
      interaction predictions into subsets of low and high confidence. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 17456609
TI  - Atherosclerosis imaging in statin intervention trials.

PMID- 17456610
TI  - Quantifying emerging drugs for very rare conditions.
AB  - BACKGROUND: EU legislation is encouraging pharmaceutical companies to develop
      drugs for rare conditions, but their often high cost, and potential for long-term
      administration has led to debate about their affordability and cost
      effectiveness. AIM: To investigate how many drugs are in development for very
      rare conditions. METHODS: We defined very rare conditions as having a prevalence
      of <1:50,000, and identified pharmaceuticals in phase II, phase III trials or pre
      registration for these conditions using commercial databases. RESULTS: We
      identified 42 very rare conditions with at least one drug in late-stage clinical
      development, with a total of 113 drugs in development (17 for at least two
      indications). Sixteen drugs were pre-registration, 29 were in phase III
      development, 65 were in phase II development, one drug was both pre-registration
      and phase II for different indications and two drugs were in both phase II and
      phase III trials for different indications. DISCUSSION: Not all the drugs in
      development will reach the market, but it is likely that a significant number
      will do so. Affordability and methods to assess cost-effectiveness will need
      debate and clear national policy for decision-makers to follow.

PMID- 17456611
TI  - Complications arising from intravenous buprenorphine abuse.

PMID- 17456612
TI  - Impact factor.

PMID- 17456614
TI  - Kaposi's sarcoma in renal transplant recipients--the impact of proliferation
      signal inhibitors.
AB  - The incidence of Kaposi's sarcoma (KS) is greatly increased in renal transplant
      recipients compared with the general population, with particular prevalence in
      certain ethnic groups where it can occur in up to 5% of transplant recipients.
      The increased incidence of disease in transplant populations may, in part, be
      attributed to the choice of immunosuppressive regimen, with calcineurin inhibitor
      (CNI)-based immunosuppression being associated with the development of the
      tumour. A number of small studies have recently demonstrated that conversion to
      proliferation signal inhibitors (PSIs) along with the concomitant withdrawal of
      CNIs leads to a rapid resolution of both cutaneous and visceral Kaposi's lesions.
      In agreement with these data the abrupt onset of KS has been observed following
      the withdrawal of PSIs. Histological examination of lesions from patients with KS
      supports data from animal models which suggests that PSIs inhibit tumour
      angiogenesis through impaired vascular endothelium growth factor production, a
      key element in the development of the tumour. Previously unpublished data on
      renal transplant recipients from a number of European and Australian centres have
      been pooled to provide further insight into the use of PSIs in the management of
      post-transplant KS. Both members of the PSI class, everolimus and sirolimus,
      along with CNI withdrawal lead to regression of KS lesions in 11 out of 12
      patients. Conversion to PSIs was generally well tolerated with stable renal
      function maintained in most patients and no episodes of acute rejection recorded.
      PSIs provide a potential treatment option in the management of post-transplant KS
      and should be considered for use in renal transplant recipients who develop the
      disease.

PMID- 17456615
TI  - Use of proliferation signal inhibitors in non-melanoma skin cancer following
      renal transplantation.
AB  - Non-melanoma skin cancer (NMSC) affects a large proportion of renal transplant
      recipients, with estimates suggesting that at least half of white-skinned
      transplant recipients will develop NMSC following transplantation. Squamous-cell
      carcinoma is the most frequent NMSC following transplantation occurring at a 100
      times greater risk than in the general population, while the incidence of basal
      cell carcinoma is increased 10-fold over the general population. The most
      important risk factor for the development of NMSC in renal transplant recipients
      is prior exposure to ultraviolet radiation, therefore, geographical location and
      skin type highly influence the risk of NMSC. However, both the intensity and type
      of immuno-suppressive therapy have been associated with an increased risk of
      NMSC. Given the potential anti-cancer actions of the proliferation signal
      inhibitors (PSIs), everolimus and sirolimus, demonstrated in both pre-clinical
      and clinical studies, we have analysed the effect of conversion to PSIs in 53
      renal transplant recipients developing NMSC after transplantation. Remission of
      NMSC was observed in 37 patients and was generally well tolerated with minimal
      adverse events reported. Fifteen patients developed new lesions following
      conversion, two of these were receiving low-dose calcineurin inhibitors (CNIs) as
      part of their immuno-suppressive regimen suggesting that there was insufficient
      reduction of CNIs. PSI blood levels did not seem to affect the outcomes of
      conversion. These data, along with published clinical trial data suggest that
      conversion from CNIs to PSIs may be useful in the management of NMSC following
      renal transplantation.

PMID- 17456616
TI  - Post-transplant lymphoproliferative disorder--the potential of proliferation
      signal inhibitors.
AB  - Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of
      diseases characterized by abnormal lymphoid proliferation following
      transplantation. These lymphomas, in particular, have been shown to have a higher
      incidence in renal transplant recipients compared with the general age-matched
      population. The effect of different immunosuppressive regimens on the incidence
      of PTLD has been assessed in a number of studies. Although there are conflicting
      data on the role of calcineurin inhibitors (CNIs) in promoting the development of
      PTLD, an increase in risk is described in most studies and is usually related to
      the aggressiveness of immunosuppression. The proliferation signal inhibitors
      (PSIs), everolimus and sirolimus, have both immunosuppressive and
      antiproliferative actions and pre-clinical data suggest that everolimus has an
      inhibitory effect on the growth of PTLD-derived cell lines. There is currently
      limited clinical data on the use of PSIs in the management of PTLD, therefore,
      clinical experience from nine European Transplant centres has been pooled and
      analysed to assess their potential. Conversion to PSIs and subsequent
      minimization or withdrawal of CNIs was analysed in 19 renal transplant recipients
      with PTLD and remission was observed in 15 patients. These data suggest that PSIs
      may assist with the management of PTLD following renal transplantation.

PMID- 17456617
TI  - Use of proliferation signal inhibitors in the management of post-transplant
      malignancies--clinical guidance.
AB  - Increasing success in renal transplantation and longer patient survival has meant
      that post-transplant malignancies are having an increasing impact on long-term
      graft and patient survival. Choice of the immunosuppressive agents provides one
      of the controllable risk factors for the development of malignancies in this
      population. Calcineurin inhibitors (CNIs) are associated with an increased
      incidence of cancers, whereas the proliferation signal inhibitors (PSIs),
      everolimus and sirolimus have demonstrated anti-oncogenic effects in pre-clinical
      models and are currently being investigated as anti-cancer agents in clinical
      trials. There is increasing evidence demonstrating a lower incidence of post
      transplant malignancies in renal transplant recipients receiving PSI-based
      immunosuppression compared with those receiving CNIs. Conversion from CNIs to
      PSIs has been shown to lead to the regression of Kaposi's sarcoma in renal
      transplant recipients and is now part of accepted standard care for this tumour
      in this setting. The anti-cancer properties of PSI-based regimens have the
      potential to combine the dual benefits of immunosuppression without the use of
      CNIs and the direct anti-oncogenic effects through their inhibition of the
      mammalian target of rapamycin (mTOR) signalling pathway. In the absence of formal
      clinical trial evidence on the best way to use PSIs in this setting, a workshop
      was held to provide practical guidance on immunosuppressive strategies in the
      context of malignancy, given the current state of knowledge.

PMID- 17456618
TI  - Malignancies in renal transplantation: an unmet medical need.
AB  - Registry data show that there is an overall 3-5-fold increase in cancer risk in
      transplant recipients compared with the general population, with skin cancers and
      lymphoma particularly prevalent. Cancers in transplant recipients are often more
      aggressive than those in the general population, with poor prognosis,
      particularly for gastrointestinal tumours and lymphomas. Risk factors for post
      transplant malignancy include factors common to the general population, such as
      increasing age, cigarette smoking and sun exposure. In addition,
      immunosuppression is an important factor in the development of post
      transplantation cancer, although data for individual agents are not definitive. A
      number of studies have demonstrated that ciclosporin is associated with an
      increased risk of malignancy, whereas a few studies report no increase in risk of
      cancer after the introduction of ciclosporin into treatment regimens. Similarly,
      studies have shown that the mycophenolic acid-based agent mycophenolate mofetil
      is associated with an increased risk of malignancy, whereas other studies have
      demonstrated that mycophenolate mofetil is in fact associated with a lower risk.
      Polyclonal anti-thymocyte antibodies used for induction therapy appear to be
      related to an increased incidence of post-transplant lymphoproliferative
      disorder, but this effect is not observed with monoclonal anti-interleukin 2
      antibodies. Azathioprine has been implicated in the development of skin tumours,
      possibly as a result of increased photosensitivity to ultraviolet light. The
      proliferation signal inhibitors appear to be associated with a reduced risk of
      some malignancies. Further research will elucidate the role of these newer
      immunosuppressive agents in post-transplantation malignancies.

PMID- 17456619
TI  - Potential thrombogenic complications with the use of recombinant activated factor
      VII in combat trauma.

PMID- 17456620
TI  - Amaurosis fugax caused by heritable thrombophilia-hypofibrinolysis in cases
      without carotid atherosclerosis: thromboprophylaxis prevents subsequent transient
      monocular partial blindness.
AB  - Nineteen patients (age 60 +/- 14) with amaurosis fugax associated with heritable
      thrombophilia-hypofibrinolysis without ipsilateral atherosclerotic carotid plaque
      or other causes of amaurosis fugax were studied. Our hypothesis was that case
      specific thromboprophylaxis would prevent subsequent amaurosis fugax episodes.
      Prospective treatment data were available for 13 cases. Thrombophilic disorders
      included high Factors VIII and XI, G20210A prothrombin heterozygosity, low
      proteins C and S, MTHFR mutations, and the PL A1/A2 mutation. Hypofibrinolytic
      disorders included plasminogen activator inhibitor-1 4G4G, and high lipoprotein
      (a). Treatments included Coumadin; Lovenox, folic acid-vitamin B6-vitamin B12,
      discontinuation of estrogens-selective estrogen receptor modulators, Glucophage,
      and aspirin, as appropriate. Usually within 1 month on therapy, patients became
      asymptomatic and have remained asymptomatic for > or = 1 year on therapy, without
      adverse treatment side effects. When amaurosis fugax occurs without carotid
      artery atherosclerosis or other known causes, thrombophilia or hypofibrinolysis,
      or both are nearly universal, safely treatable, reversible pathoetiologies.

PMID- 17456621
TI  - Prevention of influenza episodes with colostrum compared with vaccination in
      healthy and high-risk cardiovascular subjects: the epidemiologic study in San
      Valentino.
AB  - The efficacy of a 2-month treatment with oral colostrum in the prevention of flu
      episodes compared with antiinfluenza vaccination was evaluated. Groups included
      healthy subjects without prophylaxis and those receiving both vaccination and
      colostrum. After 3 months of follow-up, the number of days with flu was 3 times
      higher in the non-colostrum subjects. The colostrum group had 13 episodes versus
      14 in the colostrum + vaccination group, 41 in the group without prophylaxis, and
      57 in nontreated subjects. Part 2 of the study had a similar protocol with 65
      very high-risk cardiovascular subjects, all of whom had prophylaxis. The
      incidence of complications and hospital admission was higher in the group that
      received only a vaccination compared with the colostrum groups. Colostrum, both
      in healthy subjects and high-risk cardiovascular patients, is at least 3 times
      more effective than vaccination to prevent flu and is very cost-effective.

PMID- 17456622
TI  - Isolation and characterization of heparin from tuna skins.
AB  - This study characterized heparin isolated from tuna skins. Glycosaminoglycans
      were isolated from tuna skin after digestion using anion exchange resin. Heparin
      was eluted from the resin by sodium chloride gradient and was further
      fractionated by acetone fractionation. Anticoagulant activity was determined
      using the activated partial thromboplastin time and Heptest assays. Potency was
      determined using amidolytic antifactor IIa and antifactor Xa assays. The presence
      of heparin in the extracted tuna skin glycosaminoglycans was confirmed using
      (13)C-nuclear magnetic resonance. The activated partial thromboplastin time and
      Heptest clotting times were doubled at concentrations of about 4 and 1 microg/mL,
      respectively. The clotting time prolongation and antiprotease activity induced by
      tuna heparin was readily neutralized by 25 microg/mL protamine sulfate. These
      results demonstrate that biologically active heparin with properties similar to
      clinical grade heparin can be derived from tuna skin, a raw material with
      otherwise relatively little economic value.

PMID- 17456623
TI  - Inhibition of thrombin in plasma by heparin or arginine.
AB  - The inhibition of plasmatic thrombin is of clinical importance in a broad range
      of diseases. To obtain reliable data the assay system should be as similar to
      physiology as possible. Using a newly developed physiologic assay system for
      fibrinogen/thrombin interaction (the FIFTA), the inhibition of plasmatic thrombin
      by heparin or by arginine was studied. The standard fibrinogen functional
      turbidimetric assay (FIFTA) was performed, varying heparin or arginine
      concentrations and varying the time point the inhibitor was added to the FIFTA.
      Plasmatic heparin concentrations equal to or greater than 0.63 IU/mL completely
      inhibit thrombin in the assay system described. The IC(50) is 0.1 IU/mL heparin.
      Heparin can only inhibit fibrin generation within the first 2 minutes at room
      temperature (RT=23 degrees C). The 50% inhibitory time point, that is, the time
      point that a 10 IU/mL final concentration of heparin results in 50% inhibition of
      FIFTA, is 30 seconds at RT. A final arginine concentration of at least 125 mM in
      the first 100 seconds of the FIFTA reaction at RT completely inhibits turbidity
      increase. Half-maximal turbidity increase occurs at 63 mM arginine. Final
      arginine concentrations of at least 250 mM completely inhibit turbidity increase,
      when arginine acts in the first 4 minutes (RT) of the thrombin/ fibrinogen
      interaction. A final arginine concentration of 477 mM added at the 12-minute or
      30-minute thrombin/ fibrinogen reaction time point decreases the resulting
      turbidity by 50% after an additional 30 minutes at RT. Pathologic disseminated
      intravascular coagulation occurs in a multitude of diseases; in common is always
      the generation of thrombin either by the contact phase or by the tissue factor
      phase of coagulation. Such pathologically elevated thrombin activity in blood or
      blood products must be prevented or inhibited. This study demonstrates the
      efficiency of two physiologic thrombin inhibitors: heparin and arginine.

PMID- 17456624
TI  - Significance of factor V, prothrombin, MTHFR, and PAI-1 genotypes in childhood
      cerebral thrombosis.
AB  - The aim of this study was to evaluate the significance of factor V (FV) G1691A,
      prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, and
      plasminogen activator inhibitor-1 (PAI-1) 4G/5G genotypes in development of
      childhood cerebral thrombosis (CT). A total of 113 Turkish children with CT were
      studied and compared with the control group. The carrier frequency of the factor
      V G1691A mutation was found to be significantly higher in the patient group
      (17.7%) than controls (7.4%). The presence of this genotype was associated with a
      2.7-fold increased risk of developing CT (95% confidence interval [CI], 1.0-7.0).
      The prevalence of prothrombin G20210A mutation in 110 patients (4.5%) was
      insignificantly higher than controls (2.3%) (odds ratio, 2.0; 95% CI, 0.4-10.7).
      A statistically significant increase in the frequency of homozygous MTHFR C677T
      genotype was observed in 62 patients (11.3%) compared to controls (4.3%), and
      this genotype was associated with 2.8-fold increased CT risk (95% CI, 1.0-8.0).
      The incidence of PAI-1 4G/4G genotype in 65 patients (21.5%) was slightly lower
      than that of controls (26.0%), but the differences did not reach statistical
      significance (odds ratio, 0.8; 95% CI, 0.4-1.5). The results of this study
      suggested that factor V G1691A and MTHFR C677T genotypes may be associated with
      an increased risk of developing CT in Turkish children.

PMID- 17456625
TI  - Treatment of deep vein thrombosis with enoxaparin in pediatric cancer patients
      receiving chemotherapy.
AB  - There are few data regarding the use of enoxaparin in children undergoing
      myelosuppressive therapy for malignancies even though thrombosis is a known risk
      in pediatric patients with malignancies. Low-molecular-weight heparin such as
      enoxaparin has become widely used in adult patients with thrombosis. The purpose
      of this study was to review the utilization of low-molecular-weight heparin,
      enoxaparin (Lovenox), in children with cancer at our institution who had
      thrombosis while undergoing myelosuppressive chemotherapy. In particular we were
      interested in the efficacy of enoxaparin in these patients, and in whether these
      children were able to continue their chemotherapy without adjustment or
      interruption secondary to bleeding complications. We conducted a retrospective
      review from 1999 through April 1, 2004. Seven patients (4-17 years of age) were
      identified. Diagnosis included B-precursor acute lymphoblastic leukemia (ALL)
      (n=three), T-ALL, Hodgkin's disease, anaplastic large cell lymphoma, and
      rhabdomyosarcoma (n=one each). Six patients had a deep vein thrombus (DVT) or
      clot of the vena cava. One of these six patients also had a pulmonary embolus.
      One patient presented with manifestations of a unilateral cerebral vascular
      accident without evidence of DVT. Most patients were screened for known
      hypercoaguable abnormalities. Treatment was enoxaparin, 1-1.5 mg/kg/dose twice
      daily to maintain a heparin anti-Xa level of 0.5-1.5 IU/mL till clot resolution.
      The dose was then decreased to daily for a total of 3-6 months of therapy. All
      patients had resolution of their thrombosis within 1-2 months of initiation of
      enoxaparin, and none required delays or dose reduction of their chemotherapy
      regimens while on anticoagulation, though some were supported by blood and
      platelet transfusions. Enoxaparin was safely administered to this series of seven
      patients for thrombotic complications in children undergoing cancer chemotherapy.

PMID- 17456626
TI  - The frequency of factor V Leiden and concomitance of factor V Leiden with
      prothrombin G20210A mutation and methylene tetrahydrofolate reductase C677T gene
      mutation in healthy population of Denizli, Aegean region of Turkey.
AB  - Factor V Leiden causing activated protein C resistance is the most common
      inherited form of thrombophilia leading to thrombosis. Its frequency shows great
      ethnic and geographic variations. The aim of this study was to determine the
      frequency of FV Leiden and coinheritance of FV Leiden with two other frequent
      hereditary thrombophilia causes, namely, prothrombin G20210A and methylene
      tetrahydrofolate reductase (MTHFR) C677T mutation in the Aegean region of Turkey.
      The study population consisted of 1030 (500 men and 530 women) apparently healthy
      subjects. Functional resistance to activated protein C (APC) was measured by
      using the test kit STA staclot APC-R ((Diagnostica Stago, Asnieres, France, Cat.
      No. 00721). In subjects with APC resistance, molecular analyses of FV Leiden and
      of prothrombin G20210A and MTHFR C677T mutation were performed by using FV-PTH
      MTHFR StripA (Vienna Lab, Labordiagnostika GmbH, Austria) kit, which was based on
      hybridization of polymerase chain reaction (PCR) amplified DNA products with
      mutation-specific oligonucleotide probes. Functional APC resistance was present
      in 93 subjects (9%). FV Leiden mutation was found in 87 of 93 subjects with APC
      resistance by PCR method. The FV Leiden carrier frequency was found to be 8.4%
      (87/1030). Seventy-six individuals were heterozygous (7.3%), and 11 were
      homozygous (1.06%). Among the 87 subjects with FV Leiden mutation, 45 subjects
      had MTHFR C677T gene mutation (7 homozygous, 38 heterozygous) and 4 subjects had
      heterozygote prothrombin G20210A gene mutation. A combination of FV Leiden and
      prothrombin G20210A and MTHFR C677T gene mutation was detected in 3 subjects. The
      results indicate that FV Leiden prevalence is quite high and coexistence of FV
      Leiden with other hereditary causes of thrombosis such as prothrombin G20210A
      mutation and MTHFR enzyme defect is not rare in healthy population of Aegean
      region of Turkey.

PMID- 17456627
TI  - A Prospective comparison of new Japanese criteria for disseminated intravascular
      coagulation: new Japanese criteria versus ISTH criteria.
AB  - In Japan, early diagnosis and early treatment of disseminated intravascular
      coagulation (DIC) based on the old Japanese criteria have greatly improved the
      outcomes of DIC patients with hematopoietic malignancy. However, the prognoses of
      critically ill patients with DIC have remained poor. To overcome this situation,
      new Japanese DIC criteria for critically ill patients were established in 2002.
      The new Japanese DIC criteria adopted a concept of coagulopathy associated with
      systemic inflammatory response syndrome. In the present study, we prospectively
      investigated the relationships between the new criteria and organ failure,
      prognosis, and other sets of DIC criteria. This study included 74 patients whose
      platelet counts were below 150 x 10(9)/L. Daily DIC scores and sequential organ
      failure assessment scores were recorded from days 0 to 4 once the patient was
      included in the study. The new Japanese DIC criteria diagnosed DIC earlier than
      both the non-overt DIC and the old Japanese criteria did (P = .0005). The new
      Japanese criteria diagnosed more DIC patients prior to the establishment of
      multiple organ failure than the other sets (P = .023). The new Japanese criteria
      tended also to predict prognoses more efficiently than the other two sets. In
      conclusion, the diagnostic sensitivity of the new Japanese criteria was as high
      as that of the non-overt DIC criteria. Furthermore, the new Japanese criteria
      provided the earliest detection and most accurate outcome prediction of DIC among
      the DIC criteria sets.

PMID- 17456628
TI  - Heparin-induced thrombocytopenia in a uremic patient requiring hemodialysis: an
      alternative treatment and reexposure to heparin.
AB  - Heparin-induced thrombocytopenia (HIT) is an uncommon but potentially serious
      complication of hemodialysis, and subsequent reexposure to heparin after the
      disappearance of antiheparin-PF4 complex antibodies (HIT antibody) has been
      controversial. We report a 60-year-old woman who was sensitized to unfractionated
      heparin (heparin) as anticoagulant during hemodialysis (HD) and heparin flush on
      a nonsession day. The patient suddenly developed acute systemic reactions with
      acute pulmonary embolism a few minutes after manipulation with heparin flush on
      day 9, a nonsession day. Although there was no evidence of pulmonary embolism on
      a pulmonary scintigram on the next day, the fifth HD session was discontinued
      owing to recurrence of acute systemic reactions and massive clots in the dialyzer
      30 min into the session. After confirmation of the presence of HIT antibody and
      maturation of vascular access fistula, a sixth HD session was carried out with
      argatroban, a synthetic direct thrombin inhibitor, with a bolus of 10 mg and
      continuous infusion of 0.5 mg/kg/hr as an alternative to heparin. Optimal dose
      adjustment of argatroban through activated partial thromboplastin time (APTT)
      monitoring led to a bolus of 5 mg and continuous infusion of 0.15 mg/kg/hr. The
      patient's HD treatment at the same doses 3 times a week followed an uneventful
      course over 6 months. HIT antibody was seronegative about 40 days after the
      cessation of heparin treatment. Reexposure to heparin was attempted with the
      monitoring of HIT antibody and platelet counts before and after the sessions on
      day 210. The titers of HIT antibody compared with before the level of reexposure
      showed a transient insignificantly small peak, and dialysis with heparin has been
      maintained to date with no recurrence of HIT. The measurement of HIT antibody
      titer could be useful in assessing not only the effect of argatroban to replace
      heparin but also in predicting the recurrence of HIT due to reexposure.

PMID- 17456629
TI  - Lower contribution of factor V Leiden or G202104 mutations to ischemic stroke in
      patients with clinical risk factors: pair-matched case-control study.
AB  - It was suggested that factor V Leiden and prothrombin G20210A mutations increase
      the risk of ischemic stroke only in combination with clinical risk factors of
      arterial ischemic disease. In these studies the controls were derived from the
      general population, with fewer clinical risk factors, which might have produced
      biased results. The factor V Leiden and prothrombin G20210A mutations were
      examined by polymerase chain reaction technique in 120 ischemic stroke patients
      and 120 controls younger than 65 years of age. Each patient had his own control,
      tightly matched in clinical risk factors. The prevalences of factor V Leiden and
      prothrombin G20210A mutations in patients were 8.3% (P = 0.02) and 7.5% (P =
      0.04), respectively, and 2.5% for controls for both mutations. All carriers were
      single heterozygotes. In patients, but not in controls, the carriers of either
      mutation were mostly women and with fewer clinical risk factors for arterial
      ischemic events. In particular, considering both mutations as a single
      coagulation deficit, their presence increased the likelihood of ischemic stroke
      (odds ratio [OR] = 3.6; 95% confidence interval [CI] 1.4-9.3), especially among
      women (OR = 4.6; 95% CI: 1.2-17.8), normotensive persons (OR = 9.2; 95% CI: 1.1
      17.8) and those having normal cholesterol (OR = 5.9; 95% CI: 1.6-21.2) and
      triglyceride serum concentrations (OR = 4.3; 95% CI: 1.5-12.8). In the studied
      sample of adult North Mediterranean population younger than 65 years the
      prevalences of factor V Leiden and prothrombin G20210A mutations were greater in
      patients with ischemic stroke than in matched controls. Unlike in studies with
      unmatched controls, we observed an apparently negative interaction of these
      mutations with clinical risk factors.

PMID- 17456630
TI  - Identifying carriers of type 2N von Willebrand disease: procedures and
      significance.
AB  - The defective FVIII carrier function of von Willebrand factor (VWF) identifies
      type 2N von Willebrand disease (VWD), a variant with a pattern resembling
      hemophilia A. Type 2N characterization is based on the evaluation of the capacity
      of VWF to bind exogenous FVIII (VWF:FVIIIB). Here we report on a retrospective
      evaluation of hemostatic laboratory parameters most useful in detecting type 2N
      carriers. The diagnostic capacity of aPTT, FVIII, VWF:Ag, FVIII/VWF:Ag ratio,
      VWF:FVIIIB and VWF:FVIIIB/VWF:Ag ratio was evaluated in 21 type 2N VWD carriers.
      Twenty subjects were heterozygous for the R854Q mutation, one was heterozygous
      for the R760C missense mutation, which interferes with cleavage of the VWF
      propeptide. We found that prolongation of aPTT and decrease in FVIII and
      FVIII/VWF:Ag ratio were not frequent findings in type 2N carriers. The same was
      true for VWF:FVIIIB which was not always abnormal. On the contrary,
      VWF:FVIIIB/VWF:Ag ratio was always defective and its values were not related with
      FVIII and FVIII/VWF:Ag ratio or influenced by plasma VWF concentration. Given
      these results, we attribute the greatest significance to VWF:FVIIIB/VWF:Ag ratio
      in the diagnosis of type 2N defects, and only search for type 2N mutations, to
      validate the diagnosis, if the ratio proves abnormal.

PMID- 17456631
TI  - Increased concentration of soluble CD40 ligand in preeclampsia.
AB  - Preeclampsia has been associated with increased platelet activation detected
      before disease onset. Platelets are involved in hemostasis and also directly
      initiate an inflammatory response of the vessel wall. Inappropriate activation of
      platelets may be involved in pathogenesis in preeclampsia by promoting
      coagulation and thrombosis, and also as a mediator of inflammation. Platelets may
      release inflammatory mediators such as soluble CD40 ligand. The plasma level of
      soluble CD40 ligand was investigated during preeclamptic (n =20) and normal
      pregnancies (n = 20) to emphasize inflammatory response in preeclampsia. The mean
      soluble CD40 ligand levels were 1.08 +/- 0.43 ng/mL in patients with preeclampsia
      and 0.76 +/- 0.24 ng/mL in healthy pregnant women, which was statistically
      significant (P = .01). To clarify whether inflammation may cause inappropriate
      endothelial cell activation or inappropriate endothelial cell activation may
      start this inflammatory response, future studies are needed in a larger study
      population.

PMID- 17456632
TI  - Elevation of activated platelet-dependent chemokines in patients with anti-CD20
      monoclonal antibody (rituximab)-treated non-Hodgkin's lymphoma.
AB  - This study measured and compared levels of some chemokines in patients with
      rituximab-treated non-Hodgkin lymphoma because they may participate in the
      mechanism of efficacy of rituximab in non-Hodgkin lymphoma patients. Monocytic
      chemotactant protein-1, RANTES (regulated on activation, normally T-cell
      expressed and secreted), eotaxin, interleukin-8, neutrophil-activating protein
      78, stromal cell-derived factor-1, and growth-regulating oncogene-alpha in
      patients with rituximab-treated non-Hodgkin lymphoma were measured by enzyme
      linked immunosorbent assay. Levels of RANTES were higher in non-Hodgkin lymphoma
      patients than in controls. Levels of monocytic chemotactant protein-1, RANTES,
      and neutrophil-activating protein-78 were significantly elevated before and after
      chemotherapy with rituximab treatment. However, the level of stromal cell-derived
      factor-1 did not exhibit a significant change. Before to after chemotherapy
      without rituximab treatment, all chemokine levels did not exhibit significant
      changes. These findings suggest that activated platelet-dependent chemokines such
      as RANTES and neutrophil-activating protein-78 may modulate the efficacy of
      rituximab in antibody-dependent cellular cytotoxity.

PMID- 17456633
TI  - Arginine inhibits serpins.
AB  - Serine protease inactivators (serpins) are important regulators in biochemistry.
      Often it is necessary to block the serpin action, that is, to stabilize the
      sample. The guanidine group of arginine is the ligand for the active center
      pocket of many serine proteases. Arginine or guanidine inhibits serine proteases,
      and arginine belongs to the reactive P1-P1' center of many serpins. The plasmatic
      antithrombin, antiplasmin, or anti-C1-esterase activity was determined: A total
      of 20 microL of pooled normal plasma or 7% human albumin was added to 100 microL
      of 0-2.67 M arginine, pH 8.6, 10 microL of 26 mIU/mL thrombin in 7% human
      albumin, and 30 microL of 1.7 mM CHG-Ala-Arg-pNA (37 degrees C). DeltaA at 405 nm
      was determined, by using a microtiter plate reader. Thrombin was substituted by
      plasmin or C1-esterase, and the chromogenic peptide substrates <Glu-Phe-Lys-pNA
      or MeOC-Lys(eCBO)-Gly-Arg-pNA, respectively, were used. The IC(50) of arginine
      against plasmatic antithrombin activity is 580 mM; the IC( 25) is 440 mM. The
      IC(25) of arginine against plasmatic alpha( 2)-antiplasmin or C1-inactivator is
      1650 mM. The amidolytic activity of thrombin, plasmin, and C1-esterase is
      inhibited similarly by arginine: the IC(50) for arginine against the amidolytic
      activity of these proteases is about 400 mM. Arginine at very high concentrations
      inhibits serpins. This is important, if stabilization of a biological fluid is a
      prerequisite for valid activities of serine proteases. In addition, these high
      concentrations of arginine might be a new gentle principle to inhibit pathogens
      that need serpins for their pathophysiology.

PMID- 17456634
TI  - Heparin, myeloperoxidase, and atherosclerosis: a new focus on an old drug.

PMID- 17456635
TI  - C-reactive protein in elderly patients with suspected and confirmed pulmonary
      embolism.

PMID- 17456636
TI  - Persistence of high plasma elastase level in young subjects with acute myocardial
      infarction.

PMID- 17456637
TI  - Insulin granule trafficking in beta-cells: mathematical model of glucose-induced
      insulin secretion.
AB  - A mathematical model that represents the dynamics of intracellular insulin
      granules in beta-cells is proposed. Granule translocation and exocytosis are
      controlled by signals assumed to be essentially related to ATP-to-ADP ratio and
      cytosolic Ca(2+) concentration. The model provides an interpretation of the roles
      of the triggering and amplifying pathways of glucose-stimulated insulin
      secretion. Values of most of the model parameters were inferred from available
      experimental data. The numerical simulations represent a variety of experimental
      conditions, such as the stimulation by high K(+) and by different time courses of
      extracellular glucose, and the predicted responses agree with published
      experimental data. Model capacity to represent data measured in a hyperglycemic
      clamp was also tested. Model parameter changes that may reflect alterations of
      beta-cell function present in type 2 diabetes are investigated, and the action of
      pharmacological agents that bind to sulfonylurea receptors is simulated.

PMID- 17456638
TI  - Impaired adaptation to repeated restraint and decreased response to cold in
      urocortin 1 knockout mice.
AB  - Urocortin 1 (UCN1) is a corticotropin-releasing factor (CRF)-like peptide whose
      role in stress is not well characterized. To study the physiological role of UCN1
      in the response of the hypothalamic-pituitary-adrenal (HPA) axis to stress, we
      generated UCN1-knockout (KO) mice and examined their adaptation to repeated
      restraint and to cold environment. Wild-type (WT) and UCN1-KO animals were
      restrained hourly for 15 min from 9 AM to 2 PM, and blood samples were obtained
      for corticosterone measurement. WT animals adapted to repeated restraint with a
      decreased corticosterone response; the restraint-stimulated corticosterone levels
      fell from 215 +/- 31 ng/ml in naive animals to 142 +/- 50 ng/ml in mice subjected
      to repeated restraint (P < 0.01) and from 552 +/- 98 to 314 +/- 58 ng/ml (P <
      0.001) in males and females, respectively. Male UCN1-KO mice did not show any
      adaptation to repeated restraint; instead, restraint-stimulated corticosterone
      levels were increased from 274 +/- 80 ng/ml in naive animals to 480 +/- 75 ng/ml
      in mice subjected to repeated restraint (P < 0.001). Female UCN1-KO mice showed
      only a partial adaptation to repeated restraint, with a decrease in the restraint
      stimulated corticosterone response from 631 +/- 102 ng/ml in naive animals to 467
      +/- 78 ng/ml in mice subjected to repeated restraint (P < 0.01). In addition,
      UCN1-KO mice showed no corticosterone response to 2-h cold environment. These
      data demonstrate an important role for UCN1 in the HPA axis adaptation to
      repeated restraint and in the corticosterone response to a cold environment.

PMID- 17456639
TI  - Growth hormone regulation of metabolic gene expression in muscle: a microarray
      study in hypopituitary men.
AB  - Muscle is a target of growth hormone (GH) action and a major contributor to whole
      body metabolism. Little is known about how GH regulates metabolic processes in
      muscle or the extent to which muscle contributes to changes in whole body
      substrate metabolism during GH treatment. To identify GH-responsive genes that
      regulate substrate metabolism in muscle, we studied six hypopituitary men who
      underwent whole body metabolic measurement and skeletal muscle biopsies before
      and after 2 wk of GH treatment (0.5 mg/day). Transcript profiles of four subjects
      were analyzed using Affymetrix GeneChips. Serum insulin-like growth factor I (IGF
      I) and procollagens I and III were measured by RIA. GH increased serum IGF-I and
      procollagens I and III, enhanced whole body lipid oxidation, reduced carbohydrate
      oxidation, and stimulated protein synthesis. It induced gene expression of IGF-I
      and collagens in muscle. GH reduced expression of several enzymes regulating
      lipid oxidation and energy production. It reduced calpain 3, increased ribosomal
      protein L38 expression, and displayed mixed effects on genes encoding
      myofibrillar proteins. It increased expression of circadian gene CLOCK, and
      reduced that of PERIOD. In summary, GH exerted concordant effects on muscle
      expression and blood levels of IGF-I and collagens. It induced changes in genes
      regulating protein metabolism in parallel with a whole body anabolic effect. The
      discordance between muscle gene expression profiles and metabolic responses
      suggests that muscle is unlikely to contribute to GH-induced stimulation of whole
      body energy and lipid metabolism. GH may regulate circadian function in skeletal
      muscle by modulating circadian gene expression with possible metabolic
      consequences.

PMID- 17456640
TI  - Glucocorticosteroid-induced osteoporosis in adult primiparous Gottingen miniature
      pigs: effects on bone mineral and mineral metabolism.
AB  - Information on the pathophysiology of glucocorticoid-induced osteoporosis (GIO)
      is limited, since its clinical picture often reflects a combined effect of
      glucocorticoids (GC) and the treated systemic disease (i.e., inflammation and
      immobility). In 50 healthy adult (30-mo-old) primiparous Gottingen minipigs, we
      studied the short-term (8 mo, n = 30) and long-term (15 mo, n = 10) effect of GC
      on bone and mineral metabolism longitudinally and cross-sectionally compared with
      a control group (n = 10). All animals on GC treatment received prednisolone
      orally at a dose of 1.0 mg x kg body wt(-1) x day(-1) for 8 wk and thereafter at
      0.5 mg/kg body wt(-1) x day(-1). In the short term, GC reduced bone mineral
      density (BMD) at the lumbar spine by -47.5 +/- 5.1 mg/cm(3) from baseline (P <
      0.001), which was greater (P < 0.05) than the loss [not significant (NS)] in the
      control group of -11.8 +/- 12.6 mg/cm(3). Calcium absorption decreased from
      baseline by -2,488 +/- 688 mg/7 days (P < 0.001) compared with -1,380 +/- 1,297
      mg/7 days (NS) in the control group. Plasma bone alkaline phosphatase (BAP)
      decreased from baseline by -17.8 +/- 2.2 U/l (P < 0.000), which was significantly
      different (P < 0.05) from the value of the control group of -1.43 +/- 4.8 U/l. In
      the long term, the loss of BMD became more pronounced and bone mineral content
      (BMC), trabecular thickness, mechanical stability, calcium absorption, 25
      hydroxyvitamin D(3), 1,25-dihydroxyvitamin D(3), and parathyroid hormone tended
      to be lower compared with the control group. There was a negative association
      between the cumulative dose of GC and BMD, which was associated with impaired
      osteoblastogenesis. In conclusion, the main outcomes after GC treatment are
      comparable to symptoms of GC-induced osteoporosis in human subjects. Thus the
      adult Gottingen miniature pig appears to be a valuable animal model for GC
      induced osteoporosis.

PMID- 17456643
TI  - The athlete of "a certain age".

PMID- 17456642
TI  - Electrothermal arthroscopic shoulder capsulorrhaphy: a minimum 2-year follow-up.
AB  - BACKGROUND: Few studies have documented the outcomes of thermal capsulorrhaphy
      for shoulder instability. PURPOSE: To examine prospective evaluate outcomes of
      the first 100 patients with glenohumeral instability treated with thermal
      capsulorrhaphy. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Between
      1997 and 1999, 85 of 100 patients treated with thermal capsulorrhaphy for
      glenohumeral instability were available for review at 2-year minimum follow-up
      (average, 4 years). Fifty-one patients suffered from anterior instability; 24 had
      an associated Bankart lesion. Ten patients demonstrated posterior instability; 1
      had an associated reverse Bankart lesion. Seventeen patients had multidirectional
      instability; 8 had an associated Bankart lesion. Seven patients demonstrated
      anterior and posterior instability without an inferior component; 2 had an
      associated Bankart lesion. Failures were defined as shoulders requiring revision
      stabilization (14) or with recurrent instability (18), recalcitrant pain (3), or
      stiffness (2). RESULTS: Forty-eight of 85 procedures were successful, and 37 of
      85 failed. For patients with anterior instability plus a Bankart lesion, 7 of 24
      (26%) had failed results. For those with anterior instability without a Bankart
      lesion, 10 of 27 (33%) had failed results. The failure rates for posterior,
      multidirectional instability, and anteroposterior were 60% (6/10), 59% (10/17),
      and 57% (4/7), respectively. Of the 48 successes, mean preoperative American
      Shoulder and Elbow Surgeons score improved from 71 to 96 postoperatively, and
      patient satisfaction was 9.1 on a 10-point scale. CONCLUSION: Because of the high
      failure rates, we now augment thermal capsulorrhaphy with capsular plication
      and/or rotator interval closure in cases of posterior and multidirectional
      instability and have lengthened the initial immobilization period to improve
      outcomes. Failure rates for thermal capsulorrhaphy, even with labral repairs, are
      high especially for shoulders with multidirectional instability and posterior
      instability. When procedures were successful, however, patients were very
      satisfied with significant improvements in American Shoulder and Elbow Surgeons
      scores.

PMID- 17456644
TI  - Ultrasound-guided regional anesthesia: in search of the holy grail.

PMID- 17456645
TI  - Should all patients undergoing cardiac surgery have preoperative psychometric
      testing: a brain stress test?

PMID- 17456646
TI  - Gender differences in stroke risk among the elderly after coronary artery
      surgery.
AB  - BACKGROUND: Previous studies have shown that women are at higher risk than men
      for stroke after coronary artery bypass graft (CABG) surgery, but gender
      differences in systemic atherosclerosis have not been studied adequately. We
      investigated gender differences in the incidence of craniocervical and ascending
      aortic atherosclerosis and other risk factors for stroke in elderly patients (age
      > or =60 yr) undergoing CABG surgery. METHODS: Data were prospectively collected
      on 720 patients (31.8% women) undergoing CABG surgery. All patients underwent
      preoperative brain magnetic resonance imaging and angiography to assess for prior
      cerebral infarctions, carotid artery stenosis, and intracranial arterial
      stenosis. Epiaortic ultrasound was performed at the time of surgery to assess for
      atherosclerosis of the ascending aorta. Cognitive status was measured using the
      Hasegawa-dementia score in all patients before surgery and on the seventh
      postoperative day. RESULTS: Women were older and had more hypertension and
      intracranial arterial stenosis than did men. Men had significantly higher rates
      of hyperlipidemia, peripheral vascular disease, abdominal aortic aneurysm,
      smoking history, severe carotid artery stenosis, and severe aortic
      atherosclerosis than did women. Although there were no differences in prior
      cerebral infarction or preoperative cognitive impairment, the rate of
      perioperative stroke was marginally higher in men than in women (3.9% vs 1.3%, P
      = 0.066). Univariate predictors of perioperative stroke were prior cerebral
      infarctions, ascending aortic atherosclerosis, preexisting cognitive impairment,
      and peripheral vascular disease. Stepwise logistic regression analysis
      demonstrated that significant independent predictors of perioperative stroke were
      prior cerebral infarctions and aortic atherosclerosis. CONCLUSIONS: These data
      suggest that men are more likely than women to have risk factors for stroke,
      including severe carotid artery stenosis, severe aortic atherosclerosis, and
      peripheral vascular disease. The rates of prior cerebral infarction and
      preoperative cognitive impairment were similar between genders.

PMID- 17456647
TI  - Preexisting cognitive impairment in patients scheduled for elective coronary
      artery bypass graft surgery.
AB  - BACKGROUND: An accurate assessment of the prevalence of cognitive impairment in
      patients scheduled for coronary artery bypass graft (CABG) surgery is necessary
      if valid assumptions regarding cognitive change are to be made. Such an
      assessment requires the use of a healthy control group free of cardiovascular
      disease. METHODS: In a retrospective observational study, 349 patients scheduled
      for CABG surgery underwent neuropsychological testing. We compared the results
      with those from a group of 170 healthy controls without cardiovascular disease
      and containing more female patients who were matched for age and IQ score.
      Cognitive impairment was defined as test scores > or =2 sd less than the controls
      on two or more of the seven tests. RESULTS: The CABG surgery patients performed
      significantly worse than the control group on all tests except the Grooved
      Pegboard test (nondominant). When analyzed by group, performance on the verbal
      learning test was the most impaired. Cognitive impairment was present in 122
      (35%) of CABG surgery patients before their procedure. Prior myocardial
      infarction, age, and IQ were independent predictors of cognitive impairment.
      CONCLUSIONS: Cognitive impairment is prevalent in patients presenting for CABG
      surgery. Impaired cognition before surgery must be considered when assessing the
      effects of CABG surgery on cognitive performance.

PMID- 17456648
TI  - Pressure-controlled versus volume-controlled ventilation during one-lung
      ventilation for thoracic surgery.
AB  - BACKGROUND: Pressure-controlled ventilation (PCV) has been suggested as a tool to
      improve oxygenation during one-lung ventilation (OLV) for patients undergoing
      thoracic surgery. In this study we investigated whether PCV results in improved
      arterial oxygenation compared with volume-controlled ventilation (VCV) during
      OLV. METHODS: Fifty-eight patients with good preoperative pulmonary function
      scheduled for thoracic surgery were prospectively randomized into two groups.
      Those in group A underwent OLV initially with VCV for 30 min followed by PCV for
      a similar period of time. Those in group B underwent OLV initially with PCV for
      30 min followed by VCV for a similar duration. Airway pressures and arterial
      blood gases were obtained during OLV at the end of each ventilatory mode.
      RESULTS: There were no differences during OLV in arterial oxygenation between VCV
      (Pao2, 206.1 +/- 62.4 mm Hg) and PCV (Pao2, 202.1 +/- 56.4 mm Hg; P = 0.534).
      Peak airway pressure was lower with PCV than with VCV (24.43 +/- 3.42 cm H2O vs.
      34.16 +/- 5.21 cm H2O; P < 0.001). CONCLUSIONS: The use of PCV during OLV does
      not lead to improved oxygenation during OLV compared with VCV for patients with
      good preoperative pulmonary function, but PCV did lead to lower peak airway
      pressures. Further study is needed for patients with severe obstructive or
      restrictive pulmonary disease.

PMID- 17456649
TI  - Cerebral oxygen desaturation after cardiopulmonary bypass in a patient with
      raynaud's phenomenon detected by near-infrared cerebral oximetry.
AB  - Raynaud's phenomenon is characterized by episodes of arterial vasospasm
      precipitated by cold stress, usually affecting the digits of the hands. There is
      controversy about the occurrence of vasospasm in internal organ systems. In this
      report, we present a case of Raynaud's peripheral vasospasm accompanied by
      cerebral oxygen desaturation as detected by near infrared cerebral oximetry after
      separation from cardiopulmonary bypass.

PMID- 17456650
TI  - Spontaneous echocardiographic contrast indicating successful endoleak management.

PMID- 17456651
TI  - Postoperative ketorolac tromethamine use in infants aged 6-18 months: the effect
      on morphine usage, safety assessment, and stereo-specific pharmacokinetics.
AB  - BACKGROUND: Nonsteroidal antiinflammatory drugs have been useful for treating
      postoperative pain in children. The only parenteral nonsteroidal antiinflammatory
      drug currently available in the United States is ketorolac tromethamine with
      cyclooxygenase-1 and cyclooxygenase-2 effects. Information on the
      pharmacokinetics of ketorolac in infants is sparse, making dosing difficult.
      Ketorolac is administered as a racemic mixture with the S(-) isomer responsible
      for the analgesic effect. In this study, we describe the population
      pharmacokinetics of ketorolac in a group of 25 infants and toddlers who received
      a single IV administration of racemic ketorolac and evaluate the potential
      influence of patient covariates on ketorolac disposition. METHODS: In this double
      blind, placebo-controlled study, ketorolac pharmacokinetic, safety, and analgesic
      effects were studied in 37 infants and toddlers (aged 6-18 mo) postoperatively.
      On postoperative day 1, infants were randomized to receive placebo, 0.5, or 1
      mg/kg ketorolac as a 10-min IV infusion. Blood samples were collected up to 12-h
      after dosing. The data were analyzed using noncompartmental and compartmental
      (nonlinear mixed-effects model) means. The patient covariates, including body
      weight, age, and surgical procedure, were analyzed in a stepwise fashion to
      identify their potential influence on ketorolac pharmacokinetics. RESULTS: The
      data were best described by a two-compartmental model. Inclusion of covariates
      did not significantly decrease the nonlinear mixed-effects model objective
      function values and between-subject variability in the pharmacokinetic parameters
      of nested models. The mean and standard error of the estimates of the R(+) isomer
      were central volume of distribution 1200 +/- 163 mL (coefficient of variation of
      interindividual variability, 13.6%), peripheral volume of distribution 828 +/-
      108 mL (13.0%), clearance from the central compartment 7.52 +/- 0.7 mL/min
      (9.3%), and extrapolated elimination half-life 238 +/- 48 min. Those of the S(-)
      isomer were 2320 +/- 34 (14.6%), 224 +/- 193 mL (86.2%), 45.3 +/- 5.5 mL/min
      (12.1%), and 50 +/- 42 min respectively. Dosing simulations, using population
      pharmacokinetic parameters, showed no accumulation of S(-) ketorolac but steady
      increases in R(+) ketorolac. Safety assessment showed no adverse effects on renal
      or hepatic function tests, surgical drain output, or continuous oximetry between
      placebo and ketorolac groups. Cumulative morphine administration showed large
      interpatient variability and was not different between groups. CONCLUSION: The
      stereo-isomer-specific clearance of ketorolac in infants and toddlers (aged 6-18
      mo) shows rapid elimination of the analgesic S(-) isomer. No adverse effects on
      surgical drain output, oximetry measured saturations, renal or hepatic function
      tests were seen. Simulation of single dosing at 0.5 or 1 mg/kg every 4 or 6 h
      does not lead to accumulation of S(-) ketorolac, the analgesic isomer, but does
      result in increases in R(+) ketorolac. Shorter dose intervals may be needed in
      infants older than 6 mo.

PMID- 17456652
TI  - There is no dose-escalation response to dexamethasone (0.0625-1.0 mg/kg) in
      pediatric tonsillectomy or adenotonsillectomy patients for preventing vomiting,
      reducing pain, shortening time to first liquid intake, or the incidence of voice
      change.
AB  - BACKGROUND: Tonsillectomy is associated with postoperative nausea and vomiting
      (PONV) if no prophylaxis is administered. Previous studies have shown that a
      single dose of dexamethasone decreases the incidence of PONV. The most effective
      dose of dexamethasone to affect clinical outcome is yet to be defined. METHODS:
      One-hundred-twenty-five children were enrolled in a double-blind, prospective,
      randomized, dose-escalating study of dexamethasone: 0.0625, 0.125, 0.25, 0.5, or
      1 mg/kg, maximum dose 24 mg. Nonparametric ANOVA was used to analyze the
      incidence of vomiting by treatment group for 0 to < or =5 h, >5 to 24 h. The Cox
      Proportional Likelihood Ratio Test was used to compare the time of first vomit
      and time to first pain medication across treatment groups. RESULTS: There was no
      difference in the incidence of vomiting for the five escalating doses of
      dexamethasone in the time period. There were no differences in secondary outcomes
      (analgesic requirements, time to first liquid, and change in voice) across
      treatment groups. CONCLUSION: We conclude that the lowest dose of dexamethasone
      (0.0625 mg/kg) was as effective as the highest dose of dexamethasone (1.0 mg/kg)
      for preventing PONV or reducing the incidence of other secondary outcomes
      following tonsillectomy or adenotonsillectomy. There is no justification for the
      use of high-dose dexamethasone for the prevention of PONV in this cohort of
      children.

PMID- 17456653
TI  - Time course and prognostic value of plasma B-type natriuretic peptide
      concentration in neonates undergoing the arterial switch operation.
AB  - BACKGROUND: Plasma B-type natriuretic peptide (BNP) can predict postoperative
      complications after cardiac surgery in adults. Our aim was to investigate BNP
      kinetics and prognostic value in neonates undergoing the arterial switch
      operation (ASO) for transposition of the great arteries (TGA). METHODS: We
      measured BNP concentrations in 30 neonates before, immediately after, and 6, 12,
      24, and 48 h after ASO for TGA. Complicated postoperative evolution was defined
      as patients requiring mechanical ventilation or presenting low cardiac output
      syndrome for more than 72 h. We studied the ability of postoperative BNP
      concentrations to predict complicated evolution. RESULTS: Intubation duration,
      inotropic support duration, and intensive care unit stay were 68 (48-121) h, 78
      (69-141) h, and 96 (76-149) h respectively. Patients with complicated evolution
      had higher 6 and 12-h BNP concentrations than patients with simple evolution (459
      (210-897) vs 137 (67-248) ng/L and 547 (193-868) vs 185 (79-354) ng/L
      respectively; P < 0.05) and had longer intubation, inotropic support, and
      intensive care unit stay (96 (70-190) vs 50 (48-66) h, 100 (83-190) vs 70 (59-72)
      h, and 120 (90-240) vs 84 (72-96) h, P < 0.05). A 6-h BNP concentration >160 ng/L
      was able to predict complicated evolution with a sensitivity of 93% and a
      specificity of 67%. CONCLUSION: In neonates, BNP concentrations can predict
      adverse outcome in the postoperative period after ASO for TGA. This marker has
      potential clinical applications.

PMID- 17456654
TI  - Isoflurane-delayed preconditioning reduces immediate mortality and improves
      striatal function in adult mice after neonatal hypoxia-ischemia.
AB  - BACKGROUND: Exposure to hypoxia and isoflurane (Iso) before hypoxia-ischemia has
      been found to be neuroprotective in neonatal rats. We investigated the long-term
      effects of delayed preconditioning with Iso, hypoxia, or room air on motor and
      cognitive function in mice that had 65 min of hypoxia-ischemia on postnatal day
      10. METHODS: Nine-day-old C57x129T2 F1 mice received either 1.8% Iso, hypoxic
      (10% O2 in N2), or sham (room air) preconditioning. The following day, the mice
      were subjected to permanent right common carotid ligation or sham ligation
      followed by 65 min of hypoxia, or room air. At 70 days of age, learning was
      tested using a series of Morris water maze tests. Striatal function was assessed
      by response to apomorphine injection. Histological analysis was performed on
      adult brain (P120) sections of striatum and dorsal hippocampus. RESULTS: Iso
      preconditioning 24 h before severe neonatal hypoxia-ischemia reduced preweaning
      mortality from 20% to 0% (P < 0.04) and improved striatal function in adult mice,
      as assessed by circling after apomorphine injection (P < 0.028), but no
      improvements in performance were noted in the spatial-reference memory water maze
      tests. Hypoxic preconditioning improved learning relative to the sham
      preconditioned group on the hidden maze, but not the more difficult reduced maze
      test of spatial memory. It had no significant effect on preweaning mortality and
      apomorphine response. Histologic analysis showed the hippocampus of non
      preconditioned and Iso-preconditioned animals to be equally injured. CONCLUSION:
      Iso and hypoxia confer selective functional neuroprotection in a delayed
      preconditioning paradigm in neonatal mice.

PMID- 17456655
TI  - Intrathecal local anesthetic infusion as a treatment for complex regional pain
      syndrome in a child.
AB  - Diagnosis and treatment of complex regional pain syndrome in children is one of
      the most challenging clinical pain problems encountered in the chronic pain
      setting. Despite the intense and debilitating nature of the pain, referral to
      appropriate specialists often comes too late, thereby prolonging an already
      arduous (and controversial) course of treatment and risking long-term disability.
      On the contrary, full recovery can be expected with early diagnosis and prompt
      treatment. The following case study describes a novel and successful use of
      intrathecal catheter administration of ropivacaine in a child with early, rapidly
      progressing, and debilitating complex regional pain syndrome.

PMID- 17456656
TI  - A randomized, double-blind comparison of the NK1 antagonist, aprepitant, versus
      ondansetron for the prevention of postoperative nausea and vomiting.
AB  - BACKGROUND: Antiemetics currently in use are not totally effective. Neurokinin-1
      receptor antagonists are a new class of antiemetic that have shown promise for
      chemotherapy-induced nausea and vomiting. This is the first study evaluating the
      efficacy and tolerability of the neurokinin-1 receptor antagonist, aprepitant,
      for the prevention of postoperative nausea and vomiting. METHODS: In this
      multicenter, double-blind trial, we randomly assigned 805 patients receiving
      general anesthesia for open abdominal surgery to a preoperative dose of
      aprepitant 40 mg orally, aprepitant 125 mg orally, or ondansetron 4 mg IV.
      Vomiting, nausea, and use of rescue therapy were assessed over 48 h after
      surgery. Treatments were compared using logistic regression. RESULTS: Incidence
      rates for the primary end point (complete response [no vomiting and no use of
      rescue] over 0-24 h after surgery, tested for superiority of aprepitant) were not
      different across groups (45% with aprepitant 40 mg, 43% with aprepitant 125 mg,
      and 42% with ondansetron). The incidence of no vomiting (0-24 h) was higher with
      aprepitant 40 mg (90%) and aprepitant 125 mg (95%) versus ondansetron (74%) (P <
      0.001 for both comparisons), although between-treatment use of rescue and nausea
      control was not different. Both aprepitant doses also had higher incidences of no
      vomiting over 0-48 h (P < 0.001). No statistically significant differences were
      seen among the side effect profiles of the treatments. CONCLUSIONS: Aprepitant
      was superior to ondansetron for prevention of vomiting in the first 24 and 48 h,
      but no significant differences were observed between aprepitant and ondansetron
      for nausea control, use of rescue, or complete response.

PMID- 17456657
TI  - Anesthetic properties of some fluorinated oxolanes and oxetanes.
AB  - BACKGROUND: The search for new potent inhaled anesthetics has slowed, in large
      part because of the excellence of the two most recent additions, desflurane and
      sevoflurane. Nonetheless, neither desflurane nor sevoflurane are ideal
      anesthetics, desflurane causing cardiorespiratory stimulation, and sevoflurane
      having a slower (albeit rapid) recovery from anesthesia. Sevoflurane also can
      produce convulsions and postoperative agitation. METHODS AND RESULTS: In the
      present report, we describe the physical and anesthetic properties of 31 cyclic
      ethers halogenated solely with fluorine. Although several produced anesthesia,
      none had solubilities that would make them better than sevoflurane. The remaining
      ethers were unstable or produced obvious central nervous system irritation,
      including convulsions. CONCLUSIONS: We find that none of these cyclic ethers
      appear to provide advantages over desflurane or sevoflurane.

PMID- 17456658
TI  - Lidocaine, MK-801, and MAC.
AB  - BACKGROUND: Previous studies have found that the local anesthetic/sodium channel
      blocker lidocaine decreased MAC by maximum amounts approximately equal to the
      decreases produced by dizocilpine (MK-801), a N-methyl-d-aspartate (NMDA)
      receptor antagonist. Blockade of sodium channels by inhaled anesthetics has been
      suggested as a possible cause for impairment of transmission through NMDA
      receptors. We postulated that the net effect of lidocaine and MK-801 on MAC would
      be the same, albeit by affecting NMDA neurotransmission at different points.
      METHODS: We measured the effect of various lidocaine infusions on the MAC of
      cyclopropane, halothane, isoflurane, and o-difluorobenzene in rats. We also
      measured the effect of concurrent lidocaine-MK-801 infusion on the MAC of
      isoflurane and o-difluorobenzene. RESULTS: Our data contradicted our predictions.
      (a) We found no limit to the effect of lidocaine infusion, in some cases finding
      that lidocaine, alone, produced immobility; (b) lidocaine infusion did not
      decrease the MAC of o-difluorobenzene differently from the MAC of other inhaled
      anesthetics; and (c) the addition of MK-801 equally affected the decrease in MAC
      produced by lidocaine infusion for isoflurane versus o-difluorobenzene.
      CONCLUSION: Lidocaine does not primarily decrease MAC by decreasing the release
      of glutamate from nerve terminals.

PMID- 17456659
TI  - The effects of fentanyl on the contractile response of ovalbumin-sensitized rat
      trachea.
AB  - BACKGROUND: It is not clear whether fentanyl affects a hyperresponsive airway. We
      examined the effects of fentanyl on the contractile response of ovalbumin (OA)
      sensitized rat tracheas. METHODS: Rats were sensitized with a single
      intraperitoneal injection of 10 mug of OA mixed with adjuvant. Fourteen days
      later, the trachea was cut into 3-mm-wide rings. The OA-induced tension was
      measured, and the effects of fentanyl were studied in the presence of naloxone.
      Second, the role of cholinergic nerves and serotonin in the contraction and the
      effects of fentanyl were examined using tetrodotoxin and ketanserin. Third, lungs
      of sensitized rats were ventilated, and respiratory system resistance was
      calculated before and after the administration of OA in the presence of fentanyl.
      RESULTS: Fentanyl dose-dependently attenuated the OA-induced contraction, and
      naloxone partly reversed it. Both tetrodotoxin and ketanserin attenuated the
      contraction. Fentanyl had no further effect on the contraction in the presence of
      tetrodotoxin, whereas the contraction was nearly abolished by fentanyl in the
      presence of ketanserin. OA increased respiratory system resistance in sensitized
      rats, and this effect was attenuated by fentanyl. CONCLUSIONS: Fentanyl
      attenuates the airway hyperresponsiveness of sensitized rat trachea through the
      inhibition of cholinergic nerves on the smooth muscle.

PMID- 17456660
TI  - The effects of systemic lidocaine on airway tone and pulmonary function in
      asthmatic subjects.
AB  - BACKGROUND: To prevent reflex-induced bronchoconstriction in patients with
      asthma, local anesthetics are commonly administered by aerosol or IV as adjunct
      medication. Lidocaine attenuates responsiveness to a neurally active stimulus
      that increases tone, but there is scant information about the effect of lidocaine
      on baseline airway tone. Therefore we examined the effects of IV lidocaine on
      baseline airway tone in asthmatic subjects. METHODS: Small, medium, and large
      airways (2-5, 5-8, >8 mm diameter) were analyzed by computed tomography in 15
      asthmatic volunteers under baseline conditions and during infusion of lidocaine.
      Changes in luminal airway diameter and wall thickness from baseline to during
      lidocaine infusion, and the change in pulmonary function induced by lidocaine,
      were analyzed. RESULTS: Lidocaine caused a significant decrease in the forced
      expiratory volume in 1 s pulmonary function measure (7 +/- 2%, P = 0.006). There
      was also a small but significant decrease in the airway luminal diameter at total
      lung capacity during lidocaine infusion compared to baseline (-3 +/- 0.5%, P <
      0.001). Moreover, there was a significant correlation between the change in
      forced expiratory volume in 1 s and the change in airway luminal diameter at
      total lung capacity (r2 = 0.47, P = 0.01). CONCLUSION: Lidocaine, which reduces
      airway responsiveness to drugs that cause bronchospasm through sensory nerve
      activation, did not reduce baseline airway tone. Instead, even when administered
      IV, lidocaine significantly increased airway tone and caused airway narrowing.
      Therefore, while the administration of lidocaine can prevent intubation-induced
      bronchospasm, the airways should be constantly monitored by auscultation even
      during IV lidocaine administration.

PMID- 17456661
TI  - Lack in effects of therapeutic concentrations of dexmedetomidine and clonidine on
      the neuromuscular blocking action of rocuronium in isolated rat diaphragms.
AB  - BACKGROUND: We investigated the effects of the alpha-2 adrenoceptor agonists
      clonidine and dexmedetomidine on the neuromuscular blocking effect of rocuronium
      in vitro. METHODS: Isometric twitch tensions of rat nerve-hemidiaphragm
      preparations elicited by indirect (phrenic nerve) supramaximal stimulation at 0.1
      Hz were evaluated. RESULTS: Clonidine and dexmedetomidine 50 microM (n = 6 each),
      but not 0.05 microM, shifted the rocuronium concentration-twitch tension curves
      to the left and decreased the rocuronium concentration for 50% twitch depression
      (IC50) compared with control (n = 9, P < 0.01). The leftward shift induced by
      clonidine 50 microM or dexmedetomidine 50 microM was not antagonized by yohimbine
      50 microM, an alpha-2 adrenoceptor antagonist. Twitch tensions partially
      depressed by 7 microM rocuronium, to about 65% of the control, were further
      suppressed in a concentration-dependent manner by clonidine (n = 6) and
      dexmedetomidine (n = 9) at concentrations of 30 microM or more (P < 0.01).
      CONCLUSIONS: These results indicate that very high, but not therapeutic,
      concentrations of clonidine and dexmedetomidine enhance the neuromuscular
      blocking action of rocuronium, but this is not mediated by an agonist action on
      alpha-2 adrenoceptors.

PMID- 17456662
TI  - Prolongation of intrathecal and sciatic nerve blocks using a complex of
      levobupivacaine with maltosyl-beta-cyclodextrin in rats.
AB  - BACKGROUND: We used a cyclodextrin-based drug delivery system, consisting of
      levobupivacaine complexed with maltosyl-beta-cyclodextrin (G2-beta-CD), in spinal
      and sciatic nerve blocks in rats to investigate prolongation of the local
      anesthetic effect. METHODS: Rats were assigned to four groups (n = 6 in each) and
      received intrathecally 30 microL of 1% levobupivacaine complexed with 0
      (control), 50, 100, or 200 mM of G2-beta-CD. Muscle tone and tail flick latency
      were studied after intrathecal administration. Four more groups (n = 6) of rats
      received a sciatic nerve block with 0.5% or 1% levobupivacaine complexed with
      either 0 or 100 mM of G2-beta-CD. The time course of changes in proprioception,
      motor function, and nociception after circumferential subcutaneous administration
      to the sciatic nerve was examined. RESULTS: With the intrathecal block, all rats
      stopped tail movement immediately after injection of the local anesthetic. The
      mean time to recovery of muscle tone with 1% levobupivacaine complexed with 100
      mM (80.0 +/- 8.9 min) and 200 mM (91.7 +/- 7.0 min) of G2-beta-CD was
      significantly longer than that of the control group (38.3 +/- 3.1 min), but tail
      flick latency was not prolonged. With the sciatic nerve block, all rats were
      temporarily immobilized after levobupivacaine injection. The anesthetic effects
      of 0.5% levobupivacaine with 100 mM of G2-beta-CD were twice as long as those for
      0.5% levobupivacaine alone, and those of 1% levobupivacaine with 100 mM of G2
      beta-CD were 1.4 times longer than those for 1% levobupivacaine alone.
      CONCLUSIONS: The complex of levobupivacaine with G2-beta-CD prolonged the
      anesthetic effect of levobupivacaine in both intrathecal and sciatic nerve blocks
      in rats.

PMID- 17456663
TI  - The effects of sevoflurane anesthesia on rat brain proteins: a proteomic time
      course analysis.
AB  - BACKGROUND: Recent studies showed changes in cerebral protein expression up to 3
      days after desflurane anesthesia in rats. In the present study, we investigated
      the existence of persisting changes on the proteome level after sevoflurane
      anesthesia that persisted for as long as 28 days after anesthesia. METHODS: Rats
      were anesthetized by spontaneous inhalation of 2.4% sevoflurane in air for 3 h.
      Animals (n = 6 for each group) were killed either directly, 72 h, or 28 days
      after anesthesia. Brains were removed and subjected to global protein expression
      profiling based on two-dimensional gel electrophoresis and mass spectrometry.
      Expression factors were compared to results from untreated conscious animals at
      each time point. Data were statistically analyzed by ANOVA (P < 0.01) and a cut
      of more than two-fold change in the expression factor. RESULTS: We found 11
      protein spots differentially regulated directly after anesthesia. Seventeen
      proteins were differentially expressed 72 h after the anesthesia. Only one spot
      was differentially regulated 28 days after anesthesia. The plausible targets of
      these differentially regulated proteins can be attributed to synaptic vesicle
      handling and cell-cell communication. CONCLUSIONS: Sevoflurane induced relevant
      changes in protein expression profiles directly and 72 h after an anesthesia with
      1 MAC. Twenty-eight days after the anesthesia, all proteins except one had
      returned to baseline levels of abundance.

PMID- 17456664
TI  - The effects of general anesthetics on P2X7 and P2Y receptors in a rat microglial
      cell line.
AB  - BACKGROUND: Microglial cells play important roles in coordinating the
      inflammatory brain responses to hypoxia and trauma. Ionotropic P2X receptors and
      metabotropic P2Y receptors (P2YRs) expressed in microglia can be activated by
      extracellular adenosine triphosphate (ATP) derived from damaged cells or
      astrocytes, and participate in the signaling pathways evoked in brain insult.
      Although several inhaled and IV anesthetics produce neuroprotective effects
      through neuronal mechanisms, little is known about how general anesthetics
      modulate microglial responses in the pathological state. We examined the effects
      of various general anesthetics on purinergic responses in a rat microglial cell
      line. METHODS: Currents were consistently activated by applications of ATP via a
      U-tube system under the whole-cell configuration. ATP-induced nondesensitizing
      currents observed after several applications of ATP exhibited characteristics of
      P2X7 receptors. The P2YRs-mediated mobilization of intracellular Ca2+ was
      measured using a Ca2+-sensitive fluorescent dye (fura-2). RESULTS: Inhaled
      anesthetics (sevoflurane, isoflurane, and halothane) at doses three times as high
      as minimum alveolar concentrations had no effect on the P2X7Rs-mediated currents.
      IV anesthetics (ketamine, propofol, and thiopental) enhanced the P2X7Rs-mediated
      currents reversibly. The potencies for activation of P2X7Rs were not correlated
      with the octanol/buffer partition coefficients. Thiopental, at low
      concentrations, slightly inhibited the P2X7Rs-mediated currents, suggesting its
      dual actions on P2X7Rs. The P2YRs-mediated mobilization of intracellular Ca2+ was
      not affected by any of the general anesthetics tested. CONCLUSIONS: Our results
      suggest that IV anesthetics, particularly thiopental and propofol, may modulate
      microglial functions through P2X7Rs in pathological conditions.

PMID- 17456665
TI  - Bispectral index-guided general anesthesia in combination with thoracic epidural
      analgesia reduces recovery time in fast-track colon surgery.
AB  - BACKGROUND: The impact of bispectral index (BIS)-guided general anesthesia on
      recovery from general anesthesia has been evaluated in different patient
      populations. The benefit of using BIS has been inconsistent. We designed this
      study to examine the value of BIS-guided anesthesia in a fast-track setting where
      the goal is rapid recovery. METHODS: Forty-four patients undergoing open colon
      resection were randomly assigned to receive either BIS-guided (BIS group, n = 22)
      or clinically guided (standard care group, n = 22) total IV anesthesia with
      propofol after placing a thoracic epidural catheter. Duration of postanesthesia
      care unit stay, time to tracheal extubation, direct drug cost, the incidence of
      hemodynamic abnormalities, ability of ambulation on the day of surgery, and
      patient satisfaction with anesthetic management were assessed. RESULTS: In the
      BIS-guided group, tracheal extubation was achieved significantly earlier (7.6 vs.
      15.4 min, P < 0.01) and the postanesthesia care unit stay was significantly
      shorter (51 vs. 85 min, P < 0.01). Total anesthetic drug cost was reduced by 23%
      and the incidence of hypotension requiring treatment was significantly lower in
      the BIS group. Early ambulation, patient satisfaction, and incidence of adverse
      events were not significantly different between the groups. CONCLUSIONS: BIS
      guided IV anesthesia in combination with thoracic epidural analgesia facilitates
      rapid recovery and reduces the overall cost of care in patients undergoing fast
      track colon surgery.

PMID- 17456666
TI  - The influence of stellate ganglion transcutaneous electrical nerve stimulation on
      signal quality of pulse oximetry in prehospital trauma care.
AB  - BACKGROUND: Accurate monitoring of the peripheral arterial oxygen saturation has
      become an important tool in the prehospital emergency medicine. This monitoring
      requires an adequate plethysmographic pulsation. Signal quality is diminished by
      cold ambient temperature due to vasoconstriction. Blockade of the stellate
      ganglion can improve peripheral vascular perfusion and can be achieved by direct
      injection or transcutaneous electrical nerve stimulation (TENS) stimulation. We
      evaluated whether TENS on the stellate ganglion would reduce vasoconstriction and
      thereby improve signal detection quality of peripheral pulse oximetry. METHODS:
      In our study, 53 patients with minor trauma who required transport to the
      hospital were enrolled. We recorded vital signs, including core and skin
      temperature before and after transport to the hospital. Pulse oximetry sensors
      were attached to the patient's second finger on both hands. TENS of the stellate
      ganglion was started on one side after the beginning of the transport. Pulse
      oximeter alerts, due to poor signal detection, were recorded for each side
      separately. RESULTS: On the hand treated with TENS we detected a significant
      reduction of alerts compared to the other side (mean alerts TENS 3.1 [1-15]
      versus control side 8.8 [1-28] P < 0.05). The duration of dropouts was shorter as
      well (mean duration TENS 77 [16-239] s versus control side 333 [78-1002] s).
      CONCLUSION: The data indicate that blockade of the stellate ganglion with TENS
      improves signal quality of pulse oximeters in the prehospital setting.

PMID- 17456667
TI  - The novel use of computer-generated virtual imaging to assess the difficult
      pediatric airway.
AB  - In a patient with a known difficult airway, history and examination may be of
      limited use in formulating a management plan for subsequent tracheal intubation.
      Further detailed and descriptive review of the airway is necessary. Virtual
      imaging is a recent advance in radiology that offers noninvasive airway
      assessment. It creates a movie clip image of the upper airway akin to the view
      obtained through a fiberscope. We present a patient with Goldenhar syndrome in
      whom virtual imaging was used to identify the cause of a previous failed tracheal
      intubation.

PMID- 17456668
TI  - Application of a similarity index to state discharge abstract data to identify
      opportunities for growth of surgical and anesthesia practices.
AB  - INTRODUCTION: Most surgical and anesthesia groups are interested in expanding
      their practices and recruiting more patients. Methods have been developed to help
      hospitals identify surgical specialties with the potential for growth by
      determining whether the hospital is performing fewer of certain types of
      procedures than expected in a given specialty. However, these methods are not
      appropriate for physicians who may practice at more than one hospital and want to
      determine the potential for growth in their regions. METHODS: We examined
      potential markets for growth of surgical and anesthesia practices in Iowa and New
      York State using state discharge abstract data. Several patient demographic
      groups and several surgical specialties were examined. Each state was divided
      into regions, and data were analyzed three ways: (1) A similarity index compared
      each region to the rest of the state. (2) The number of procedures performed on
      patients who left their home regions for care was determined. (3) A similarity
      index compared procedures performed on patients who left their home regions for
      care with procedures performed on patients who remained within their home
      regions. RESULTS: The methods successfully identified several geographic regions
      with previously unrecognized growth potential. Access to care was limited in
      these regions. The methods correctly showed few opportunities for growth in
      geographic regions where expansion was already known to be unlikely. CONCLUSIONS:
      A count of the number of procedures performed on patients who left their home
      regions, in combination with the similarity index, is a useful method for
      screening state discharge abstract data to identify geographic regions where
      surgical and anesthesia practices could grow.

PMID- 17456669
TI  - The effects of hypothermia on endotoxin-primed lung.
AB  - BACKGROUND: Hypothermia may be effective for endotoxin-induced acute lung injury.
      In most studies, hypothermia was induced before the development of neutrophilic
      inflammation, which would be clinically irrelevant. We investigated whether
      hypothermia induced after the onset of such neutrophilic inflammation reduces
      acute lung injury. METHODS: In the first experiment, rats were allocated to one
      of four groups: intratracheal saline instillation/killed at 1 h (saline),
      intratracheal lipopolysaccharide (LPS) instillation/killed at 1 h (LPS-primed),
      intratracheal LPS instillation/killed at 6 h (LPS-NT), all under normothermia
      (NT) (37 +/- 0.5 degrees C) throughout study, and intratracheal LPS
      instillation/killed at 6 h with hypothermia (HT) (32 +/- 0.5 degrees C) for the
      last 5 h of study (LPS-HT). Lungs were lavaged for biochemical measurements. In
      the second experiment in 26 additional rats, we followed exactly the same
      protocol as described above for the saline group (n = 2), LPS-NT (n = 12), and
      LPS-HT (n = 12), and obtained a fresh pool of alveolar neutrophils to assess
      oxidative burst. RESULTS: Compared with the LPS-primed group, the neutrophil
      count, protein level, and lactate dehydrogenase activity in the bronchoalveolar
      lavage fluid, and myeloperoxidase activity of the lung were all higher in the LPS
      NT group. Compared with this LPS-NT group, the neutrophil count, protein level,
      and lactate dehydrogenase activity in the bronchoalveolar lavage fluid, and
      microscopic scores for alveolar neutrophilic infiltration were all lower in the
      LPS-HT group. The stimulated production of hydrogen peroxide in neutrophils was
      lower in the LPS-HT group than in the LPS-NT group. CONCLUSION: Hypothermia,
      applied even after the onset of neutrophilic inflammation, was effective in
      reducing endotoxin-induced acute lung injury.

PMID- 17456670
TI  - Sigma receptor agonists provide neuroprotection in vitro by preserving bcl-2.
AB  - BACKGROUND: Sigma (sigma)-receptor agonists attenuate brain injury after
      experimental focal cerebral ischemia in several species. We tested the hypothesis
      that the potent, prototypical sigma(1)-receptor agonist, 4-phenyl-1-(4
      phenylbutyl) piperidine (PPBP), protects neurons by a mechanism involving the
      antiapoptotic protein bcl-2. METHODS: Primary cortical neuronal cultures were
      exposed to either 2 h of oxygen-glucose deprivation (OGD) or glutamate (100
      microM). PPBP treatment was initiated either 15 min prior to the insult or at 15
      min postinsult then continued for 24 h. In another set of experiments, cultured
      neurons were preincubated for 2 h prior to PPBP treatment with sigma1-receptor
      antagonist, rimcazole, in a dose-dependent manner. Alive and dead cells were
      detected with calcein-AM and propidium iodide respectively. Bcl-2 and bax
      expression were determined by quantitative real time reverse transcription
      polymerase chain reaction and western blotting, and DNA damage was detected by
      TUNEL staining. RESULTS: PPBP pretreatment attenuated neuronal injury induced by
      OGD or glutamate (50 or 100 microM). This protection was reversed with rimcazole
      (cell death: OGD 48 +/- 2%, OGD plus PPBP 31 +/- 3%, OGD plus PPBP with rimcazole
      46 +/- 2%). PPBP treatment increased bcl-2 but not bax mRNA levels. PPBP's
      ability to preserve bcl-2 protein after OGD by PPBP was fully abolished by
      rimcazole. Lastly, PPBP reduced the number of TUNEL-positive cells after OGD,
      suggesting fewer cells with overt DNA damage. CONCLUSIONS: These data demonstrate
      that PPBP reduces cell death in vitro by a mechanism involving receptor-dependent
      preservation of protective genes such as bcl-2.

PMID- 17456671
TI  - Visual loss in a prone-positioned spine surgery patient with the head on a foam
      headrest and goggles covering the eyes: an old complication with a new mechanism.
AB  - A patient developed central retinal artery occlusion during surgery in the prone
      position with eye protectors placed over his eyes. We discuss the potential
      hazards of using such a device (the Dupaco Opti-Gard) in this setting.

PMID- 17456672
TI  - Ultrasound using the transverse approach to the lumbar spine provides reliable
      landmarks for labor epidurals.
AB  - BACKGROUND: Ultrasound imaging of the spine has recently been proposed to
      facilitate identification of the epidural space. In this study, we assessed the
      accuracy and precision of the transverse approach, using a "single-screen"
      method, to facilitate labor epidurals. METHODS: We enrolled 61 patients
      requesting labor epidurals. Ultrasound imaging (transverse approach, 2-5 MHz
      curved array probe) identified the midline, the intervertebral space, and the
      distance from the skin to the epidural space (ultrasound depth/UD). During the
      epidural puncture, we recorded the success of the insertion point, and measured
      the distance to the epidural space to the nearest half-centimeter of the marked
      Tuohy needle (needle depth/ND). We calculated the agreement between UD and ND by
      the concordance correlation coefficient and Bland-Altman analysis with 95% limits
      of agreement. RESULTS: The average maternal age was 33 +/- 4.6 yr, body mass
      index 29.7 +/- 4.8, UD 4.66 +/- 0.68 cm, and ND 4.65 +/- 0.72 cm. The success of
      the insertion point was 91.8%, with no need to redirect the needle in 73.8% of
      the patients. The concordance correlation coefficient between UD and ND was 0.881
      (95% CI 0.820-0.942). The 95% limits of agreement were -0.666 to 0.687 cm.
      CONCLUSIONS: We found a good level of success in the ultrasound-determined
      insertion point, and very good agreement between UD and ND. This suggests that
      our proposed ultrasound single-screen method, using the transverse approach, can
      be a reliable guide to facilitate labor epidural insertion.

PMID- 17456673
TI  - Cesarean delivery in the interventional radiology suite: a novel approach to
      obstetric hemostasis.
AB  - BACKGROUND: The adjunctive use of interventional radiology procedures to minimize
      and control bleeding at the time of cesarean delivery has become increasingly
      common. These procedures require modern imaging equipment and supplies not
      available in traditional operating rooms. METHODS: We describe three women who
      strongly desired continued reproductive function in clinical circumstances where
      postpartum hemorrhage and hysterectomy were likely. RESULTS: Cesarean delivery
      was performed in the interventional radiology suite after selective uterine
      artery balloon placement and/or embolotherapy, which successfully minimized blood
      loss during delivery. CONCLUSION: We propose that this novel surgical location is
      feasible, and may offer advantages in select patients.

PMID- 17456674
TI  - Cricoid pressure impedes insertion of, and ventilation through, the ProSeal
      laryngeal mask airway in anesthetized, paralyzed patients.
AB  - BACKGROUND: We designed this prospective self-controlled study to assess whether
      cricoid pressure hampers placement of and ventilation through the ProSeal
      laryngeal mask airway (ProSeal LMA) in anesthetized, paralyzed adult patients.
      METHODS: After induction of anesthesia, the ProSeal LMA was inserted using the
      introducer tool with cricoid pressure advanced as far as possible, and the cuff
      pressure was set at 60 cm H2O. Ventilation adequacy and anatomic position were
      scored using measures previously described for ProSeal LMA assessment. Airway
      seal pressure was recorded. Cricoid pressure was then released, the ProSeal LMA
      further advanced and reseated, and the assessment repeated. RESULTS: Lung
      ventilation scores, anatomic position scores, and airway seal pressure were
      significantly better after release of cricoid pressure and reseating of the
      ProSeal LMA than in the first position, where the ProSeal LMA was seated with
      cricoid pressure (P < 0.05). Expiratory tidal volume during intermittent positive
      pressure ventilation was similar with and without cricoid pressure, but peak
      inspiratory pressure decreased from 28 cm H(2)O with cricoid pressure to 14 cm
      H(2)O without cricoid pressure (P < 0.05). CONCLUSIONS: Cricoid pressure applied
      before insertion hampered proper placement of the ProSeal LMA. Temporary cricoid
      pressure release during insertion allowed the device to be advanced to the proper
      position. After correct placement of the ProSeal LMA, application of cricoid
      pressure did not change tidal volume, but produced a significant increase in peak
      inspiratory pressure.

PMID- 17456675
TI  - Hypnosis and surgery: past, present, and future.
AB  - Hypnosis has been defined as the induction of a subjective state in which
      alterations of perception or memory can be elicited by suggestion. Ever since the
      first public demonstrations of "animal magnetism" by Mesmer in the 18th century,
      the use of this psychological tool has fascinated the medical community and
      public alike. The application of hypnosis to alter pain perception and memory
      dates back centuries. Yet little progress has been made to fully comprehend or
      appreciate its potential compared to the pharmacologic advances in
      anesthesiology. Recently, hypnosis has aroused interest, as hypnosis seems to
      complement and possibly enhance conscious sedation. Contemporary clinical
      investigators claim that the combination of analgesia and hypnosis is superior to
      conventional pharmacologic anesthesia for minor surgical cases, with patients and
      surgeons responding favorably. Simultaneously, basic research of pain pathways
      involving the nociceptive flexion reflex and positron emission tomography has
      yielded objective data regarding the physiologic correlates of hypnosis. In this
      article I review the history, basic scientific and clinical studies, and modern
      practical considerations of one of the oldest therapeutical tools: the power of
      suggestion.

PMID- 17456676
TI  - Perineural resiniferatoxin prevents the development of hyperalgesia produced by
      loose ligation of the sciatic nerve in rats.
AB  - BACKGROUND: The vanilloid receptors (TRPV1) are found in peripheral nerve fibers;
      their stimulation by capsaicin leads to release of calcitonin gene-related
      peptide and other neuropeptides participating in neuroinflammation. On the other
      hand, various inflammatory mediators, released after nerve damage, can activate
      or sensitize the TRPV1 receptors. These findings together suggest a protective
      effect of TRPV1 receptor blockade in neuropathy. In the present study, we tested
      the hypothesis that perineural resiniferatoxin (RTX) can prevent the development
      of hyperalgesia caused by placing loosely constrictive ligatures around the
      sciatic nerve. METHODS: Male Sprague-Dawley rats received a single percutaneous
      injection of RTX (0.0005%, 0.1 mL) or vehicle at the sciatic nerve, and underwent
      surgery 3 h later to place four loose ligatures around the nerve on the side of
      drug administration. Responses to noxious heat (withdrawal latency, paw-lift
      duration), repetitive stimulation with von Frey filaments, and changes in hindpaw
      posture (toe spread, ventroflexion, and foot exorotation) were assessed. RESULTS:
      Perineural RTX administered before surgery completely prevented ligation-induced
      reduction in withdrawal latency, increase in paw lift duration and increase in
      withdrawal frequency to von Frey filaments. The preventive effect of RTX on the
      development of deficits in hindpaw posture was pronounced but not complete, e.g.,
      on day 7 after surgery, the cumulative paw-posture score (0-6) was 1.69 +/- 0.92
      with RTX and 4.06 +/- 1.68 with vehicle (P < 0.005). The effect of RTX used
      against the background of already developed neuropathy was limited to thermal
      hypoalgesia lasting for a relatively short period. CONCLUSION: Perineural RTX
      prevents the development of neuropathy caused by placing loosely constrictive
      ligatures on the sciatic nerve. Perioperative use of drugs acting via the TRPV1
      receptors may hold the promise for preventing neuropathic pain after surgery on
      peripheral nerves.

PMID- 17456677
TI  - The efficacy of lumbar epidural steroid injections in patients with lumbar disc
      herniations.
AB  - INTRODUCTION: Lumbar epidural steroid injection can be accomplished by one of
      three methods: caudal (C), interlaminar (IL), or transforaminal (TF). In this
      study we sought to determine the efficacy of these techniques for the management
      of radicular pain associated with lumbar disk herniations. METHODS: Ninety
      patients aged 18-60 years with L5-S1 disk herniations and radicular pain were
      randomly assigned to one of these groups to have epidural steroid injection
      therapy every 2 wk for a maximum of three injections. Pain relief, disability,
      and activity levels were assessed. RESULTS: Pain relief was significantly more
      effective with TF injections. At 24 wk from the initiation of this study, pain
      relief was as follows: C: complete pain relief: 1/30, partial pain relief: 16/30,
      and no relief: 13/30; IL: complete pain relief: 3/30, partial pain relief: 15/30,
      and no relief: 12/30; and TF: complete pain relief: 9/30, partial pain relief:
      16/30, and no relief: 5/30. CONCLUSIONS: The TF route of epidural steroid
      placement is more effective than the C or IL routes. We attribute this
      observation to a higher incidence of steroid placement in the ventral epidural
      space when the TF method is used.

PMID- 17456678
TI  - Disruption of attention and working memory traces in individuals with chronic
      pain.
AB  - BACKGROUND: Research has found that chronic pain disrupts attention and that this
      disruption can lead to significant functional impairment and decreased quality of
      life. We conducted the present study to examine how attention and memory are
      disrupted by chronic pain. METHODS: Computerized tests of working memory were
      given to participants with chronic pain along with a neuropsychological test of
      attention before and after procedures resulting in analgesia. RESULTS: Two-thirds
      of participants with chronic pain had scores in the clinically impaired range on
      attentional tasks. These results were independent of age, education level, sleep
      disruption, and pain relief. Medication use was also recorded and is reported to
      account for potential effects of medication on task performance. Those
      participants with the highest level of impairment had significantly greater
      difficulties in maintaining a memory trace during a challenging test of working
      memory. CONCLUSIONS: These findings point to a specific cognitive mechanism, the
      maintenance of the memory trace, that is affected by chronic pain during task
      performance. Cognitive function was not improved by short-term local analgesia.

PMID- 17456679
TI  - Epidural clonidine for postoperative pain after total knee arthroplasty: a dose
      response study.
AB  - BACKGROUND: Combinations of epidural clonidine, local anesthetics, and opioids
      have improved postoperative analgesia after total knee arthroplasty. In this
      study we sought to determine the optimal epidural bolus dose of clonidine, which
      provides the best analgesia and fewest side effects. METHODS: Eighty ASA I-III
      patients, who underwent total knee arthroplasty were randomly assigned to one of
      four groups of 20 patients each. Identical epidural anesthesia procedures were
      used for all groups. After surgery, groups C0, C1, C2, and C4 received patient
      controlled epidural analgesia (PCEA) with clonidine (0, 1.0, 2.0, or 4.0 mug/mL,
      respectively) and morphine (0.1 mg/mL) in 0.2% ropivacaine. The analgesia effect
      was estimated by PCEA consumption volume and visual analog pain scale at rest and
      with movement at 1, 2, 4, 12, 24, 48, and 72 h after surgery. Systolic blood
      pressure, heart rate, sedation, and sensory and motor blockade were also recorded
      for 72 h after surgery. RESULTS: The PCEA consumption volume for groups C0, C1,
      C2, and C4 were 71.8 +/- 19.5 mL, 49.6 +/- 12.3 mL, 48.1 +/- 9.3 mL, and 39.4 +/-
      9.0 mL, respectively. The clonidine groups experienced less postoperative pain (P
      = 0.002). In the C4 group, four patients had prolonged sensory blockade and one
      patient had both severe sedation and prolonged sensory motor blockade. No
      significant statistical difference in analgesic consumption (P = 0.78) and pain
      intensity (P = 0.66) between groups C1 and C2 were noted. CONCLUSIONS: The
      optimal amount of epidural clonidine in a solution of morphine and ropivacaine
      for postoperative pain management is 1.0 microg/mL.

PMID- 17456680
TI  - Refinement of symptoms of neuropathic pain measurements after various
      transections of the nerve endings of the sciatic and femoral nerve in rats: an
      exploratory behavioral analysis.
AB  - BACKGROUND: Many animal models can be used to study the underlying
      pathophysiological mechanisms of neuropathic pain. Most of these models rely on a
      partial denervation of the limb of the animal by ligating a selected nerve. In
      this study, we performed nerve lesions on three peripheral nerves supplying the
      plantar side of the rat hindpaw by differentially transecting the saphenous, the
      tibial, and the sural nerves alone or in paired combinations. METHODS: The
      development of neuropathic pain symptoms at three different anatomical areas
      (medial, central, and lateral) of the glabrous skin of the hindpaw was evaluated
      by sensory testing over a 12-wk period. Mechanical hyperalgesia (pinprick), cold
      allodynia (acetone), and abnormalities of hindpaw posture were continuously
      present in animals with tibial and tibial and saphenous nerve transection.
      RESULTS: Transection of the tibial and sural nerves induced cold allodynia and
      moderate mechanical hyperalgesia. Transection of the sural, the saphenous, or
      both nerves simultaneously induced no signs of specific neuropathic pain behavior
      and no abnormalities in posture of the affected hindpaw were noted after adequate
      stimulation. CONCLUSIONS: The overlapping innervation of nerve distribution can
      complicate the interpretation of nerve ligation studies of peripheral
      neuropathies.

PMID- 17456681
TI  - Estrogen amplifies pain responses to uterine cervical distension in rats by
      altering transient receptor potential-1 function.
AB  - INTRODUCTION: Estrogen sensitizes responses to painful stimuli, but its
      contribution to acute and chronic pain from the uterine cervix is unknown.
      Previous studies link the excitatory transient receptor potiential-1 channel
      (TRPV-1) to sensitization in viscera, and show that estrogen increases TRPV-1
      expression in afferents from the uterine cervix. Here, we tested whether estrogen
      enhanced responses to uterine cervical distension in rats, and whether this
      involved TRPV-1 channels. METHODS: Ovariectomized rats, with or without estrogen
      replacement, were anesthetized and hypogastric nerve and abdominal muscle
      contraction reflex responses to graded uterine cervical distension were recorded.
      Single unit hypogastric nerve fiber firing was measured before and after acute
      treatment with the TRPV-1 antagonist, capsaizepine, or vehicle. RESULTS:
      Abdominal muscle contraction reflex responses to uterine cervical distension were
      enhanced in estrogen-treated rats. Hypogastric afferent responses to cervical
      distension were reduced by capsaizepine in estrogen-treated animals, but were
      unaffected in ovariectomized animals without estrogen replacement. CONCLUSIONS:
      These data suggest that the TRPV-1 channel is unimportant for normal
      mechanosensation in the cervix in the absence of estrogen, since capsaizepine
      failed to reduce responses to uterine cervical distension in rats without
      estrogen replacement. In contrast, TRPV-1 function is important for estrogen
      induced sensitization. These data raise the possibility that acute and chronic
      pain coming from the cervix, such as labor or cancer, may be enhanced by estrogen
      and might be reduced by antagonists of TRPV-1.

PMID- 17456682
TI  - Dextromethorphan or dextrorphan have a local anesthetic effect on infiltrative
      cutaneous analgesia in rats.
AB  - BACKGROUND: Dextromethorphan blocks sodium channels, the site of action of local
      anesthetics. In this study we evaluated whether dextromethorphan has a local
      anesthetic effect. METHODS: We administered dextromethorphan and its active
      metabolite--dextrorphan, and lidocaine subcutaneously to rats and tested them for
      cutaneous anesthesia. Drug-drug interactions and systemic safety indices
      (LD50s/ED50s) were also evaluated. RESULTS: Dextromethorphan and dextrorphan had
      a local anesthetic effect after cutaneous infiltration. The ranking of potencies
      was dextromethorphan > dextrorphan > lidocaine (P < 0.01 for each comparison). A
      combination of dextromethorphan or dextrorphan with lidocaine produced an
      additive effect. Dextromethorphan and dextrorphan had 2.4- and 1.9-fold higher
      system safety indices than did lidocaine. CONCLUSION: Dextromethorphan and
      dextrorphan were more potent local anesthetics than lidocaine, but with higher
      systemic safety indices. Coadministration of dextromethorphan or dextrorphan with
      lidocaine produced an additive effect.

PMID- 17456683
TI  - Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels.
AB  - BACKGROUND: Kv1.1 and Kv7.2/7.3 channels control excitability of neuronal cells.
      As hyperexcitability is a sign of neuropathic pain, epilepsy, and anxiety
      disorders, these channels may be important molecular targets of amitriptyline
      that cause pharmacological as well as toxicological effects by altering neuronal
      excitability. Since the molecular mechanisms underlying these effects of
      amitriptyline have not been fully elucidated, we aimed to characterize the
      interaction of amitriptyline with human Kv1.1 and Kv7.2/7.3 channels. We also
      intended to establish the interaction of amitriptyline with the Kv7.2/7.3 channel
      opener, retigabine. METHODS: Kv1.1 and Kv7.2/7.3 channels were expressed in human
      embryonic kidney cells and in Chinese hamster ovary cells. The effects of
      amitriptyline and retigabine were studied with the patch-clamp technique.
      RESULTS: Amitriptyline inhibited Kv1.1 and Kv7.2/7.3 channels in a concentration
      dependent and reversible manner. The IC50-value was 22 +/- 3 microM (n = 33) and
      10 +/- 1 microM (n = 40), respectively. Deactivating inward currents of Kv7.2/7.3
      channels were inhibited with an IC50-value of 4.2 +/- 0.6 microM (n = 32).
      Inhibition of Kv7.2/7.3 channels by amitriptyline reversibly depolarized the
      resting membrane potential. Retigabine reversed both the inhibitory action of
      amitriptyline on Kv7.2/7.3 channels as well as the depolarization of the membrane
      potential. CONCLUSIONS: Since amitriptyline inhibited Kv1.1 and Kv7.2/7.3
      channels only at toxicologically relevant plasma concentrations, our results
      suggest a role for these channels in the neuroexcitatory side effects of
      amitriptyline. As the inhibitory effects of amitriptyline were reversed by
      retigabine, a combination of amitriptyline and retigabine could be of additional
      benefit in the therapy of neuropathic pain.

PMID- 17456684
TI  - Ultrasound-guided regional anesthesia: current concepts and future trends.
AB  - The scope of ultrasound imaging guidance for regional anesthesia is growing
      rapidly. Preliminary data, although limited, suggest that ultrasound can improve
      block success rate and decrease complications. In this review, we describe the
      basic principles of ultrasound scanning and needling techniques for nerve blocks,
      highlight some of the data on clinical outcome, discuss specific limitations of
      ultrasound for regional anesthesia, and speculate on the future direction for
      physician training and competency assessment with this technology.

PMID- 17456685
TI  - Ultrasound guidance for lateral midfemoral sciatic nerve block: a prospective,
      comparative, randomized study.
AB  - Block of the sciatic nerve at the midfemoral level is usually performed using
      nerve stimulation techniques. We investigated the efficacy of ultrasound,
      combined with nerve stimulation, to locate and block the sciatic nerve at the
      lateral midfemoral level compared to nerve stimulation alone. Sixty-one patients
      scheduled for foot and ankle surgery were enrolled in this prospective,
      randomized study. Thirty patients underwent a lateral block of the sciatic nerve
      at the midfemoral level guided by ultrasound (group US) and 31 patients received
      the block without ultrasound (group ES). Once an adequate motor response was
      obtained using nerve stimulation, 35 mL of ropivacaine 0.5% was administered. The
      main end-points of the study were: number of attempts to obtain an adequate motor
      response, success rate of nerve location at the first attempt, quality and
      duration of both sensory and motor blocks, and anesthetic distribution. The
      success of sciatic nerve location at the first attempt was significantly more
      frequent in the US group than in the ES group (76.6% versus 41.9%; P < 0.001).
      The quality of the sensory block and the tolerance to the pneumatic tourniquet
      were also significantly better in the US group (P < 0.01). We conclude that
      ultrasound combined with nerve stimulation improved the quality of the sensory
      block and the tolerance to the pneumatic tourniquet, reducing the number of
      attempts to perform sciatic nerve block at the midfemoral level.

PMID- 17456686
TI  - Neurostimulation in ultrasound-guided infraclavicular block: a prospective
      randomized trial.
AB  - Ultrasound guidance (USG) for infraclavicular blocks provides real time
      visualization of the advancing needle and local anesthetic distribution. Whether
      visualization of local anesthetic spread can supplant neurostimulation as the end
      point for local anesthetic injection during USG block has never been formally
      evaluated. Therefore, for this prospective randomized study, we recruited 72
      patients scheduled for hand or forearm surgery and compared the speed of
      execution and quality of USG infraclavicular block with either USG alone (Group
      U) or USG combined with neurostimulation (Group S). In Group U, local anesthetic
      was deposited in a U-shaped distribution posterior and to each side of the
      axillary artery using as few injections as possible (1, 2, and 3 injections in
      29, 6, and 3 patients, respectively). In Group S, a single injection was made
      after obtaining a distal motor response with a stimulating current between 0.3
      and 0.6 mA. The anesthetic solution consisted of 0.5 mL/kg of lidocaine 1.5%,
      bupivacaine 0.125%, and epinephrine 1:200 000 (final concentrations). Procedure
      times were significantly shorter in Group U compared with Group S (3.1 +/- 1.6
      min and 5.2 +/- 4.7 min, respectively; P = 0.006). In Group S, anesthetic spread
      was mainly anterior to the axillary artery in 37% of patients and mainly
      posterior in 63% of patients. Thirty minutes after the injection, 86% of patients
      in Group U had complete sensory block in the musculocutaneous, median, radial,
      and ulnar nerve territories compared with 57% in Group S (P = 0.007). Patients
      blocked in Group U with a single injection had the same rate of complete block
      (86%) as those blocked with more than one injection (86%). Block supplementation
      rates were 8% in Group U versus 26% in Group S (P = 0.049). Block failure
      occurred in one patient in Group S because of an inability to obtain a distal
      stimulation after 20 min. We conclude that USG infraclavicular block is more
      rapidly performed and yields a higher success rate when visualization of local
      anesthetic spread is used as the end point for injection. Posterolateral spread
      of local anesthetic around the axillary artery predicts successful block,
      circumventing the need for direct nerve visualization.

PMID- 17456687
TI  - An ultrasonographic and histological study of intraneural injection and
      electrical stimulation in pigs.
AB  - BACKGROUND: In this study we evaluated the minimum stimulating current associated
      with intraneural needle placement and sonographic appearance of intraneural
      injection. METHODS: We inserted a needle 2 cm inside 28 pig nerves (brachial
      plexus in vivo), recorded the minimum current to elicit a motor response, and
      injected dye (5 mL) under ultrasound (US) imaging. RESULTS: The minimum current
      to elicit a motor response was 0.43 mA (range: 0.12-1.8 mA). Nerve expansion was
      visualized by US in 24 of 28 nerves. Histology revealed penetration of the
      epineurium in these same 24 nerves. There was no evidence of dysplasia within the
      fascicle of any nerve. CONCLUSIONS: US may prove useful to detect intraneural
      injection, whereas a motor response above 0.5 mA may not exclude intraneural
      needle placement. The correlation between intraneural injection and neurological
      dysfunction remains unclear.

PMID- 17456688
TI  - Ultrasound-guided infraclavicular block in an anticoagulated and anesthetized
      patient.
AB  - The author describes the use of ultrasound to facilitate a continuous
      infraclavicular brachial plexus block in a patient who had been anticoagulated
      with 5000 U of heparin. The procedure was done 2 h after the patient was
      anticoagulated, and his activated clotting time was 203 s. The patient had
      vascular checks with a laser Doppler monitor every hour and neurological checks
      every 12 h.

PMID- 17456689
TI  - The "axillary tunnel": an anatomic reappraisal of the limits and dynamics of
      spread during brachial plexus blockade.
AB  - BACKGROUND: Various anatomic factors have been described as affecting the
      distribution of a solution injected around the brachial plexus. Using
      computerized axial tomography dye studies, we introduce a new concept. METHODS:
      Ten patients with brachial plexus catheters sited using the bent needle
      supraclavicular technique were studied. After the catheter tip was located, 20 mL
      50% diluted Omnipaque dye was injected through the catheter. The limits of spread
      of dye and patterns of dye distribution were described and quantified. RESULTS:
      The brachial plexus is contained within, and closely surrounded by, rigid
      muscular and bony boundaries, which effectively create a tunnel. Tunnel unit
      volumes are small (5.21-9.5 cm3), differing significantly from the volume of dye
      injected (P < 0.001), so spread must occur along the tunnel. Tunnel dimensions
      vary, with potential points of resistance at the apex of the axilla and in the
      subcoracoid region. Catheters placed for shoulder surgery, with tips located
      inferomedial to the medial edge of the coracoid process, were associated with 90%
      retrograde flow (95% C.I. = 83-97). Catheters placed for more distal surgical
      procedures, with tips located inferolateral to the medial edge of the coracoid
      process, were associated with equally antero- and retrograde flow. CONCLUSIONS:
      We conclude that the brachial plexus is contained within a rigid-walled tunnel of
      variable dimensions, which we call the "axillary tunnel." The
      scapula/subscapularis complex, related to the subcoracoid point of resistance,
      may account for the differing patterns of dye distribution observed.

PMID- 17456690
TI  - Cognitive AIDS in a simulated anesthetic crisis.

PMID- 17456691
TI  - The real ultrasound revolution.

PMID- 17456692
TI  - Mirror-guided tracheal intubation.

PMID- 17456693
TI  - Mepivacaine overdosage is more likely a cause of intraoperative cardiac arrest
      than drug-drug interaction.

PMID- 17456694
TI  - Drug-drug interaction or a local anesthetic overdose?

PMID- 17456695
TI  - Hemostatic impairment after infusion of hydroxyethyl starch, gelatin, and
      albumin.

PMID- 17456696
TI  - Methylene blue for CPB.

PMID- 17456697
TI  - Is depth of anesthesia, as assessed by the bispectral index, related to
      postoperative cognitive dysfunction and recovery?

PMID- 17456698
TI  - Correlation of the depth of anesthesia with POCD (postoperative cognitive
      dysfunction).

PMID- 17456699
TI  - Ambulatory anesthesia: whither thou goest.

PMID- 17456700
TI  - Limitations of microarray studies.

PMID- 17456701
TI  - Aprotinin's effect on ACT is not an artifact.

PMID- 17456702
TI  - Outpatient continuous peripheral nerve catheters.

PMID- 17456703
TI  - Cricoid pressure not protective in patients that have undergone esophagectomy.

PMID- 17456704
TI  - An inflatable, multichambered upper body support for the placement of the obese
      patient in the head-elevated laryngoscopy position.

PMID- 17456705
TI  - Preoperative antibiotic administration and the surgical "time out".

PMID- 17456706
TI  - Positioning of obese patients in out-of-operating room locations.

PMID- 17456707
TI  - The LMA Fastrack endotracheal tube facilitates the use of the Bullard
      laryngoscope.

PMID- 17456708
TI  - Intravascularly administered epinephrine, injected inadvertently as part of an
      epidural test dose, failed to elicit tachycardia in a patient using timolol eye
      drops.

PMID- 17456709
TI  - Using two needles for multiple injection nerve blocks avoids manipulation after
      local anesthetic injection.

PMID- 17456710
TI  - Skin reactions at the femoral perineural catheter insertion site: retrospective
      summary of a randomized clinical trial.

PMID- 17456711
TI  - Herniation of the lateral head of the gastrocnemius muscle: is it the source of
      the posterolateral knee pain?

PMID- 17456712
TI  - Daze of the dolphin.

PMID- 17456713
TI  - Stellate ganglion block as alternative to intrathecal papaverine in relieving
      vasospasm due to subarachnoid hemorrhage.

PMID- 17456714
TI  - Laryngeal mask airway and tonsillectomy: a question of training.

PMID- 17456715
TI  - Prevention of aspiration of nasopharyngeal airway.

PMID- 17456716
TI  - Concerns about data and methodology in multiple chemical sensitivity paper.

PMID- 17456718
TI  - Developmental- and differentiation-specific patterns of human gamma- and beta
      globin promoter DNA methylation.
AB  - The mechanisms underlying the human fetal-to-adult beta-globin gene switch remain
      to be determined. While there is substantial experimental evidence to suggest
      that promoter DNA methylation is involved in this process, most data come from
      studies in nonhuman systems. We have evaluated human gamma- and beta-globin
      promoter methylation in primary human fetal liver (FL) and adult bone marrow
      (ABM) erythroid cells. Our results show that, in general, promoter methylation
      and gene expression are inversely related. However, CpGs at -162 of the gamma
      promoter and -126 of the beta promoter are hypomethylated in ABM and FL,
      respectively. We also studied gamma-globin promoter methylation during in vitro
      differentiation of erythroid cells. The gamma promoters are initially
      hypermethylated in CD34(+) cells. The upstream gamma promoter CpGs become
      hypomethylated during the preerythroid phase of differentiation and are then
      remethylated later, during erythropoiesis. The period of promoter hypomethylation
      correlates with transient gamma-globin gene expression and may explain the
      previously observed fetal hemoglobin production that occurs during early adult
      erythropoiesis. These results provide the first comprehensive survey of
      developmental changes in human gamma- and beta-globin promoter methylation and
      support the hypothesis that promoter methylation plays a role in human beta
      globin locus gene switching.

PMID- 17456719
TI  - Epitope specificity and isotype of monoclonal anti-D antibodies dictate their
      ability to inhibit phagocytosis of opsonized platelets.
AB  - Rh immune globulin (WinRho SDF; Cangene, Mississauga, ON, Canada) is an effective
      treatment for autoimmune thrombocytopenic purpura; however, maintaining a
      sustained supply for its use in autoimmune thrombocytopenic purpura and its
      primary indication, hemolytic disease of the newborn, makes the development of
      alternative reagents desirable. We compared Rh immune globulin and 6 human
      monoclonal anti-D antibodies (MoAnti-D) with differing isotypes and specificities
      for their ability to opsonize erythrocytes and inhibit platelet phagocytosis in
      an in vitro assay. Results demonstrated that opsonization of erythrocytes with Rh
      immune globulin significantly (P < .001) reduced phagocytosis of fluorescently
      labeled opsonized platelets in an Fc-dependent manner. Of the MoAnti-D that
      shared specificity but differed in isotype, only IgG3 antibodies could
      significantly (P < .001) inhibit platelet phagocytosis. In contrast, 2 MoAnti-D
      shared isotypes and differed in specificity; however, only one could
      significantly (P < .001) inhibit platelet phagocytosis. The results suggest that
      MoAnti-D epitope specificity and isotypes are critical requirements for optimal
      inhibition of opsonized platelet phagocytosis.

PMID- 17456720
TI  - Heterogeneous prognostic impact of derivative chromosome 9 deletions in chronic
      myelogenous leukemia.
AB  - Derivative chromosome 9 deletions are seen in 10% to 15% of patients with chronic
      myelogenous leukemia and have been associated with a poor prognosis; however, no
      studies have been performed in the context of a randomized clinical trial. We
      developed a DNA-based deletion screen and investigated 339 chronic phase patients
      treated with interferon-alpha as first-line therapy in 3 controlled German
      studies with a median observation time of 7 years. Deletions were detected in
      pretreatment DNA of 59 of 339 (17%) patients. Of these, 21 spanned the ABL/BCR
      junction and 38 were centromeric (n = 20) or telomeric (n = 18) of the
      breakpoint. There was no significant difference in overall survival between
      deleted and nondeleted patients. Patients with breakpoint-spanning deletions had
      poorer survival compared with patients without deletions (4.7 versus 7.8 years; P
      = .003), but this was not significant when censored at allogeneic stem cell
      transplantation (n = 129) or imatinib (n = 62) treatment in the first chronic
      phase (P = .078). Unexpectedly, deletions that did not span the breakpoint were
      associated with improved survival compared with cases without deletions (P =
      .001). Multiple Cox regression analysis indicated that deletion status (P =
      .007), age (P = .018), and spleen enlargement (P < .001) were significant
      independent indicators of survival and confirmed that only deletions spanning the
      ABL/BCR breakpoint were associated with an adverse prognosis (P = .039).

PMID- 17456721
TI  - Multiple prethymic defects underlie age-related loss of T progenitor competence.
AB  - Aging in mice and humans is characterized by declining T-lymphocyte production in
      the thymus, yet it is unclear whether aging impacts the T-lineage potential of
      hematopoietic progenitors. Although alterations in the lymphoid progenitor
      content of aged mouse bone marrow (BM) have been described, irradiation
      reconstitution experiments have failed to reveal defects in T-lineage potential
      of BM hematopoietic progenitors or purified hematopoietic stem cells (HSCs) from
      aged mice. Here, we assessed T-progenitor potential in unmanipulated recipient
      mice without conditioning irradiation. T-progenitor potential was reduced in aged
      BM compared with young BM, and this reduction was apparent at the earliest stages
      of intrathymic differentiation. Further, enriched populations of aged HSCs or
      multipotent progenitors (MPPs) gave rise to fewer T-lineage cells than their
      young counterparts. Whereas the T-precursor frequency within the MPP pool was
      unchanged, there was a 4-fold decline in T-precursor frequency within the HSC
      pool. In addition, among the T-competent HSC clones, there were fewer highly
      proliferative clones in the aged HSC pool than in the young HSC pool. These
      results identify T-compromised aged HSCs and define the nature and cellular sites
      of prethymic, age-related defects in T-lineage differentiation potential.

PMID- 17456722
TI  - A set of genes that regulate cell proliferation predicts treatment outcome in
      childhood acute lymphoblastic leukemia.
AB  - To identify novel predictors of outcome in childhood acute lymphoblastic leukemia
      (ALL), we analyzed gene expression in the leukemic cells of 187 children with
      newly diagnosed ALL and compared the findings with minimal residual disease (MRD)
      results obtained on day 19 of remission induction treatment. Genes that showed a
      significant relationship to MRD were then tested for their capacity to predict
      leukemic relapse in an independent cohort of 99 patients. We identified 674 probe
      sets that were associated with MRD on day 19 (P < .006); 40 of the identified
      genes predicted relapse (P < .03). Among these, 14 showed independent prognostic
      significance after adjustment for age, leukocyte count at diagnosis, and genetic
      subtype. More than half of the 40 genes and nearly all of the 14 genes were
      functionally related, as indicated by their roles in the regulation of cell
      proliferation. Underexpression of genes promoting cell proliferation was
      associated with resistance to chemotherapy. The biologic processes regulated by
      the genes we identified appear to be key determinants of the early cytoreductive
      response to remission induction therapy and subsequent clinical outcome in
      childhood ALL. Incorporation of the expression levels of these genes into
      existing strategies of risk classification could improve clinical management.

PMID- 17456723
TI  - Lentiviral vectors containing an enhancer-less ubiquitously acting chromatin
      opening element (UCOE) provide highly reproducible and stable transgene
      expression in hematopoietic cells.
AB  - Ubiquitously acting chromatin opening elements (UCOEs) consist of methylation
      free CpG islands encompassing dual divergently transcribed promoters of
      housekeeping genes that have been shown to confer resistance to transcriptional
      silencing and to produce consistent and stable transgene expression in tissue
      culture systems. To develop improved strategies for hematopoietic cell gene
      therapy, we have assessed the potential of the novel human HNRPA2B1-CBX3 UCOE
      (A2UCOE) within the context of a self-inactivating (SIN) lentiviral vector.
      Unlike viral promoters, the enhancer-less A2UCOE gave rise to populations of
      cells that expressed a reporter transgene at a highly reproducible level. The
      efficiency of expression per vector genome was also markedly increased in vivo
      compared with vectors incorporating either spleen focus-forming virus (SFFV) or
      cytomegalovirus (CMV) promoters, suggesting a relative resistance to silencing.
      Furthermore, an A2UCOE-IL2RG vector fully restored the IL-2 signaling pathway
      within IL2RG-deficient human cells in vitro and successfully rescued the X-linked
      severe combined immunodeficiency (SCID-X1) phenotype in a mouse model of this
      disease. These data indicate that the A2UCOE displays highly reliable
      transcriptional activity within a lentiviral vector, largely overcoming insertion
      site position effects and giving rise to therapeutically relevant levels of gene
      expression. These properties are achieved in the absence of classic enhancer
      activity and therefore may confer a high safety profile.

PMID- 17456724
TI  - Effects of age-dependent membrane transport changes on the homeostasis of
      senescent human red blood cells.
AB  - Little is known about age-related changes in red blood cell (RBC) membrane
      transport and homeostasis. We investigated first whether the known large
      variation in plasma membrane Ca(2+) (PMCA) pump activity was correlated with RBC
      age. Glycated hemoglobin, Hb A1c, was used as a reliable age marker for normal
      RBCs. We found an inverse correlation between PMCA strength and Hb A1c content,
      indicating that PMCA activity declines monotonically with RBC age. The previously
      described subpopulation of high-Na(+), low-density RBCs had the highest Hb A1c
      levels, suggesting it represents a late homeostatic condition of senescent RBCs.
      Thus, the normal densification process of RBCs with age must undergo late
      reversal, requiring a membrane permeability increase with net NaCl gain exceeding
      KCl loss. Activation of a nonselective cation channel, Pcat, was considered the
      key link in this density reversal. Investigation of Pcat properties showed that
      its most powerful activator was increased intracellular Ca(2+). Pcat was
      comparably selective to Na(+), K(+), choline, and N-methyl-D-glucamine,
      indicating a fairly large, poorly selective cation permeability pathway. Based on
      these observations, a working hypothesis is proposed to explain the mechanism of
      progressive RBC densification with age and of the late reversal to a low-density
      condition with altered ionic gradients.

PMID- 17456725
TI  - FLT3 tyrosine kinase domain mutations are biologically distinct from and have a
      significantly more favorable prognosis than FLT3 internal tandem duplications in
      patients with acute myeloid leukemia.
AB  - The prognostic impact of tyrosine kinase domain (TKD) mutations of the fms-like
      tyrosine kinase-3 (FLT3) gene in acute myeloid leukemia (AML) is currently
      uncertain. To resolve this issue we screened 1107 young adult nonacute
      promyelocytic leukemia AML patients with known FLT3 internal tandem duplication
      (ITD) status for FLT3/TKDs; they were detected in 127 (11%) cases. Mutations were
      associated with a high white cell count (P =.006) and patients with inv(16) (P =
      .005) but were infrequent in patients with adverse cytogenetics and secondary
      AML. Overall survival (OS) at 5 years was 53% and 37% for FLT3/TKD mutant and
      wild-type patients respectively (odds ratio, 0.72; 95% confidence interval, 0.58
      to 0.89; P = .002). For both the cumulative incidence of relapse and OS the
      difference in outcome between FLT3/ITDs and FLT3/TKDs was highly significant (P <
      .001). In multivariate analysis, impact of FLT3/TKDs on OS when including all
      mutant-positive patients was not significant, but patients with high-level
      mutations (more than 25% mutant) had a significantly improved outcome (P = .004).
      The novel finding that biologically distinct activating mutations of the same
      gene can be associated with markedly different clinical outcomes has implications
      for risk stratification and therapy and is significant to the understanding of
      chemoresistance in AML.

PMID- 17456726
TI  - Cellular mechanisms in sepsis.
AB  - Mortality remains very high among septic patients despite the advanced treatments
      rendered in intensive care units. The development of septic shock is
      multifactorial. Tissue damage and organ dysfunction may be caused not only by the
      microorganisms but also by the inflammatory mediators released in response to the
      infection. Cytokines (tumor necrosis factor, interleukin-1, interleukin-6,
      interleukin-8, high-mobility group box-1 protein, macrophage migratory inhibitory
      factor) and noncytokines (nitric oxide, platelet-activating factor, complements,
      and eicosonoids) may inflict tissue injury and contribute to multiple organ
      dysfunction and cell death (or apoptosis). Gram-negative bacteria are the most
      common organisms identified in septic patients. The pathological effects of gram
      negative bacteria are conveyed through lipopolysaccharide derived from the
      bacterial cell membrane. Lipopolysaccharide activates the nuclear factor kappa B,
      which triggers the release of inflammatory mediators. Protein components from
      gram-positive bacteria, fungi, or viruses may evoke the activation of nuclear
      factor kappa B in a similar fashion as lipopolysaccharide. Endogenous anti
      inflammatory mediators are released in response to the infection and act to
      control the overwhelming systemic inflammatory response. The fragile balance
      between negative and positive feedback on the inflammatory mediators is the key
      factor that modulates the cellular damage and influences the clinical outcome.

PMID- 17456727
TI  - Life-threatening complications of HIV infection.
AB  - Few modern diseases have experienced as rapid and dramatic change in prognosis
      and treatment as HIV infection. The introduction of active antiretroviral therapy
      (ART) and effective prophylaxis of opportunistic infections ushered in a new era
      in the treatment of HIV infection and changed dramatically the natural history of
      this disease. The rates of admission to the intensive care unit (ICU) and
      intensive care mortality in patients with HIV infection have shifted repeatedly
      during the AIDS epidemic, influenced by attitudes of patients and providers
      toward utility of care. In the ART era, patients with HIV infection admitted to
      the ICU fall into 3 general categories: those with AIDS-related opportunistic
      infections, those who are experiencing complications related to ART, and those
      with medical problems unrelated to HIV infection. In this article, the authors
      provide a review of the most common life-threatening complications in patients
      with HIV infection.

PMID- 17456728
TI  - Evaluation and management of patients with thrombotic thrombocytopenic purpura.
AB  - Thrombotic thrombocytopenic purpura (TTP) describes syndromes with multiple
      etiologies, some of which are rapidly fatal without plasma exchange treatment.
      Although there have been advances in understanding the pathogenesis of TTP,
      evaluation and management remain difficult because there are no specific
      diagnostic criteria, as TTP can be clinically similar to other acute disorders,
      such as sepsis, disseminated malignancy, malignant hypertension, and
      preeclampsia, and because urgent treatment is required. An unexpected observation
      of anemia and thrombocytopenia should trigger consideration of TTP; evidence that
      the anemia is due to microangiopathic hemolysis, suggested by the presence of red
      cell fragmentation on the blood smear, supports the diagnosis. When the
      diagnostic criteria of microangiopathic hemolytic anemia and thrombocytopenia
      without an apparent alternative etiology are fulfilled, plasma exchange treatment
      is appropriate. However, plasma exchange has risks for severe complications and
      death; therefore, this management decision must be balanced against the
      confidence in the diagnosis. With plasma exchange treatment, approximately 80% of
      patients survive, in contrast to only 10% in the era prior to the availability of
      plasma exchange. The continuing mortality from TTP, the risks of plasma exchange
      treatment, and the potential for recurrent episodes of TTP are clinical
      challenges that remain to be solved.

PMID- 17456729
TI  - Critical care issues in the patient after major joint replacement.
AB  - Admission rates of orthopedic patients to intensive care units are increasing.
      Thus, an intensivist's familiarity with specific problems associated with major
      joint replacement surgery is of utmost importance in order to meet the needs of
      this particular patient population. In this article, the authors review the most
      commonly encountered complications after major hip and knee arthroplasty.
      Perioperative risk factors for morbidity and mortality and the epidemiology,
      diagnosis, and treatment of cardiopulmonary complications in this patient
      population are discussed. Procedure-specific complications such as fat embolism
      and acrylic bone cement-related issues are reviewed.

PMID- 17456730
TI  - Acute adrenal insufficiency after a single dose of etomidate.
AB  - Acute adrenocortical insufficiency is a critical care emergency characterized by
      hemodynamic instability, lethargy, and cardiovascular collapse. Acute adrenal
      insufficiency has many etiologies, from rapid withdrawal of exogenous
      glucocorticoids to adrenocortical destruction to poor adrenal reserve after
      administration of steroid synthesis inhibitors. Etomidate, a parenteral hypnotic
      agent, is a steroid synthesis inhibitor. Although the use of continuous etomidate
      infusion in the intensive care unit fell from favor secondary to reports of
      adrenal crisis, single-dose etomidate for induction of anesthesia is common for
      the hemodynamically unstable patient or in patients who may not tolerate wide
      variance in heart rate or blood pressure. A case is presented of acute
      adrenocortical insufficiency and crisis after a standard induction dose of
      etomidate. Acute adrenal insufficiency should be suspected in intensive care unit
      patients who have undergone general anesthesia with etomidate induction and
      present with hypotension refractory to standard vasopressor administration.

PMID- 17456731
TI  - Cerebral oximetry monitoring provides early warning of hypercyanotic spells in an
      infant with tetralogy of Fallot.
AB  - A 3.6-kg, 3-month-old infant with a history of tetralogy of Fallot and increasing
      hypercyanotic spells was brought to the operating room for operative repair.
      Before the initiation of cardiopulmonary bypass, it was noted that an abrupt
      decrease in the cerebral oximetry value occurred before pulse oximetry measured
      the decrease in oxygen saturation. This happened 4 times, and during all 4 of the
      hypercyanotic spells, the decrease of the cerebral oximeter value occurred 15 to
      30 seconds before a change registered in the pulse oximetry value. For the first
      time, this case illustrates that cerebral oximetry monitoring may be able to
      identify the onset of hypercyanotic spells and desaturation before standard pulse
      oximetry. Cerebral oximetry may provide a quicker identification of acute changes
      in the clinical status of infants and children by identifying hypoxemia before
      pulse oximetry.

PMID- 17456732
TI  - Do not just "higher the low and lower the high".

PMID- 17456733
TI  - Extracorporeal blood purification for acute organophosphorus pesticide poisoning.

PMID- 17456735
TI  - Expression changes in mouse brains following nicotine-induced seizures: the
      modulation of transcription factor networks.
AB  - Nicotine, acting through the neuronal nicotinic acetylcholine receptors (nAChRs),
      can induce seizures in mice. We aimed to study brain transcriptional response to
      seizure and to identify genes whose expression is altered after nicotine-induced
      seizures. Whole brains of untreated mice were compared with brains 1 h after
      seizure activity, using Affymetrix U74Av2 microarrays. Experimental groups
      included wild-type mice and both nicotine-induced seizure-sensitive and 
      resistant nAChR mutant mice. Each genotype group received different nicotine
      doses to generate seizures. This approach allowed the identification of
      significantly changed genes whose expression was dependent on seizure activity,
      nicotine administration, or both but not on the type of nAChR subunit mutation or
      the amount of nicotine injected. Significant expression changes were detected in
      62 genes (P < 0.05, false discovery rate correction). Among them, gene ontology
      functional annotation analysis determined that the most significantly
      overrepresented categories were of genes encoding MAP kinase phosphatases,
      regulators of transcription and nucleosome assembly proteins. In silico
      bioinformatic analysis of the promoter regions of the 62 changed genes detected
      significant enrichments of 16 transcription regulatory elements (TREs), creating
      a network of transcriptional regulatory responses to seizures. The TREs for
      activating transcription factor and serum response factor were most significantly
      enriched, supporting their association with seizure activity. Our data suggest
      that nicotine-induced seizure in mice is a useful model to study seizure activity
      and its global brain transcriptional response. The differentially expressed genes
      detected here can help us to understand the molecular mechanisms underlying
      seizures in animal models and may also serve as candidate genes to study epilepsy
      in humans.

PMID- 17456736
TI  - Comparative genomic analysis of a mammalian beta-defensin gene cluster.
AB  - Comparative genomic analyses have yielded valuable insights into conserved and
      divergent aspects of gene function, regulation, and evolution. Herein, we
      describe the characterization of a mouse beta-defensin gene cluster locus on
      chromosome 2F6. In addition, we present the evolutionary analysis of this cluster
      and its human, rhesus, and rat orthologs. Expression analysis in mouse revealed
      the occurrence of defensin cluster transcripts in multiple tissues, with the
      highest abundance in the urogenital tract. Molecular evolutionary analysis
      suggests that this cluster originated by a series of duplication events, and by
      positive selection occurring even after the rodent-primate split. In addition,
      the constraints analysis showed higher positive selection in rodents than in
      primates, especially distal to the six-cysteine array. Positive selection in the
      evolution of these defensins may relate not only to the evolving enhancement of
      ancestral host defense but also to functional innovations in reproduction. The
      multiplicity of defensins and their preferential overexpression in the urogenital
      tract indicate that defensins function in the protection and maintenance of
      fertility.

PMID- 17456737
TI  - GeneChip, geNorm, and gastrointestinal tumors: novel reference genes for real
      time PCR.
AB  - Accurate quantitation of target genes depends on correct normalization. Use of
      genes with variable tissue transcription (GAPDH) is problematic, particularly in
      clinical samples, which are derived from different tissue sources. Using a large
      scale gene database (Affymetrix U133A) data set of 36 gastrointestinal (GI)
      tumors and normal tissues, we identified 8 candidate reference genes and
      established expression levels by real-time RT-PCR in an independent data set (n =
      42). A geometric averaging method (geNorm) identified ALG9, TFCP2, and ZNF410 as
      the most robustly expressed control genes. Examination of raw C(T) values
      demonstrated that these genes were tightly correlated between themselves (R2 >
      0.86, P < 0.0001), with low variability [coefficient of variation (CV) <12.7%]
      and high interassay reproducibility (r = 0.93, P = 0.001). In comparison, the
      alternative control gene, GAPDH, exhibited the highest variability (CV = 18.1%),
      was significantly differently expressed between tissue types (P = 0.05), was
      poorly correlated with the three reference genes (R2 < 0.4), and was considered
      the least stable gene. To illustrate the importance of correct normalization, the
      target gene, MTA1, was significantly overexpressed (P = 0.0006) in primary GI
      neuroendocrine tumor (NET) samples (vs. normal GI samples) when normalized by
      geNorm(ATZ) but not when normalized using GAPDH. The geNorm(ATZ) approach was, in
      addition, applicable to adenocarcinomas; MTA1 was overexpressed (P < 0.04) in
      malignant colon, pancreas, and breast tumors compared with normal tissues. We
      provide a robust basis for the establishment of a reference gene set using
      GeneChip data and provide evidence for the utility of normalizing a malignancy
      associated gene (MTA1) using novel reference genes and the geNorm approach in GI
      NETs as well as in adenocarcinomas and breast tumors.

PMID- 17456738
TI  - Toxicity of ligand-dependent Cre recombinases and generation of a conditional Cre
      deleter mouse allowing mosaic recombination in peripheral tissues.
AB  - Ligand-activated Cre recombinases are widely used for studying gene function in
      vitro and in conditional mouse models. To compare ligand-dependent Cre
      recombinases, different Cre estrogen receptor fusions were introduced into the
      ROSA26 locus of embryonic stem (ES) cells and assayed for genotoxicity and
      recombination efficiency. Of the tested recombinases, the CreERT2 variant showed
      no toxicity and was highly responsive to ligand induction. To constitutively
      express CreERT2 in mice and also to clarify whether the CreERT2 system displays
      background activity, we generated a knock-in mouse line harboring the CreERT2
      coding region under the control of the ROSA26 locus. Analysis of this ROSA26
      CreERT2 deleter mouse with different reporter strains revealed ubiquitous
      recombination in the embryo and partial recombination in peripheral and
      hematopoietic tissues but no effective CreERT2 expression in the brain.
      Furthermore, using flow cytometry, we found low-level background recombination in
      noninduced bitransgenic ROSA26-CreERT2/EGFP reporter mice. To determine whether
      background activity poses a general problem for conducting conditional in vivo
      experiments with the ROSA26-CreERT2 deleter, we used a sensitive conditional skin
      cancer model. In this assay, cancer induction was completely restricted to
      induced bitransgenic CreERT2/K-Ras(V12) mice, whereas noninduced control animals
      did not show any sign of cancer, indicating the usefulness of the ROSA-CreERT2
      system for regulating conditional gene expression in vivo. The ROSA26-CreERT2
      deleter strain will be a convenient experimental tool for studying gene function
      under circumstances requiring partial induction of recombination in peripheral
      tissues and will be useful for uncovering previously unknown or unsuspected
      phenotypes.

PMID- 17456739
TI  - The FliK protein and flagellar hook-length control.
AB  - The bacterial flagellum is a highly complex prokaryotic organelle. It is the
      motor that drives bacterial motility, and despite the large amount of energy
      required to make and operate flagella, motile organisms have a strong adaptive
      advantage. Flagellar biogenesis is both complex and highly coordinated and it
      typically involves at least three two-component systems. Part of the flagellum is
      a type III secretion system, and it is via this structure that flagellar
      components are exported. The assembly of a flagellum occurs in a number of
      stages, and the "checkpoint control" protein FliK functions in this process by
      detecting when the flagellar hook substructure has reached its optimal length.
      FliK then terminates hook export and assembly and transmits a signal to begin
      filament export, the final stage in flagellar biosynthesis. As yet the exact
      mechanism of how FliK achieves this is not known. Here we review what is known of
      the FliK protein and discuss the evidence for and against the various hypotheses
      that have been proposed in recent years to explain how FliK controls hook length,
      FliK as a molecular ruler, the measuring cup theory, the role of the FliK N
      terminus, the infrequent molecular ruler theory, and the molecular clock theory.

PMID- 17456740
TI  - Loop anchor modification causes the population of an alternative native state in
      an SH3-like domain.
AB  - Many stably folded proteins are proposed to contain long, unstructured loops. A
      series of hybrid proteins (EbE1-4) containing the folded scaffold of photosystem
      I accessory protein E (PsaE), an SH3-like protein, and the 40-residue heme
      binding loop of cytochrome b(5) was created to inspect the dependence of
      thermodynamic and kinetic parameters on the residues at the interface of folded
      and flexible regions. Compared to the simplest hybrid (EbE1), the chimeras
      differed by Gly insertions (EbE2, EbE3) or an asymmetric four-residue
      restructuring of loop termini (EbE4). NMR spectroscopy indicated that the
      chimeras retained the PsaE topology; native and unfolded state solubilities,
      however, were affected to varying degrees. Thermal and chemical denaturation
      experiments revealed that the EbE2 and EbE1 constructs resulted in a modest
      destabilization of the PsaE core, whereas apparent stability was increased by >5
      kJ/mol in EbE4. EbE3 aggregated at microM concentrations and was not studied in
      detail. EbE4 populated two native states (N1 and N2), which differed by
      hydrophobic core packing and C-terminal interactions. At room temperature, the
      population ratio ( approximately 3-4:1) favored the state whose spectroscopic
      properties most resembled those of PsaE (N1). EbE4 also demonstrated altered
      folding kinetics, displaying multiple slow phases related to the population of
      intermediates and possibly N2. It was concluded that loop anchors can affect
      protein properties, including stability, via short-range effects on local
      structure and long-range communication with the packed hydrophobic core.
      Modification of the attachment points appears to be a possible stepping stone in
      the transition from one three-dimensional structure to another.

PMID- 17456741
TI  - Molecular architecture of DesV from Streptomyces venezuelae: a PLP-dependent
      transaminase involved in the biosynthesis of the unusual sugar desosamine.
AB  - Desosamine is a 3-(dimethylamino)-3,4,6-trideoxyhexose found in certain macrolide
      antibiotics such as the commonly prescribed erythromycin. Six enzymes are
      required for its biosynthesis in Streptomyces venezuelae. The focus of this
      article is DesV, which catalyzes the PLP-dependent replacement of a 3-keto group
      with an amino functionality in the fifth step of the pathway. For this study the
      three-dimensional structures of both the internal aldimine and the ketimine
      intermediate with glutamate were determined to 2.05 A resolution. DesV is a
      homodimer with each subunit containing 12 alpha-helical regions and 12 beta
      strands that together form three layers of sheet. The structure of the internal
      aldimine demonstrates that the PLP-cofactor is held in place by residues
      contributed from both subunits (Asp 164 and Gln 167 from Subunit I and Tyr 221
      and Asn 235 from Subunit II). When the ketimine intermediate is present in the
      active site, the loop defined by Gln 225 to Ser 228 from Subunit II closes down
      upon the active site. The structure of DesV is similar to another sugar-modifying
      enzyme referred to as PseC. This enzyme is involved in the biosynthesis of
      pseudaminic acid, which is a sialic acid-like nonulosonate found in the flagellin
      of Helicobacter pylori. In the case of PseC, however, the amino group is
      transferred to the C-4 rather than the C-3 position. Details concerning the
      structural analysis of DesV and a comparison of its molecular architecture to
      that of PseC are presented.

PMID- 17456742
TI  - The 2.0 A crystal structure of the ERalpha ligand-binding domain complexed with
      lasofoxifene.
AB  - Lasofoxifene is a new and potent selective estrogen receptor modulator (SERM).
      The structural basis of its interaction with the estrogen receptor has been
      investigated by crystallographic analysis of its complex with the ligand-binding
      domain of estrogen receptor alpha at a resolution of 2.0 A. As with other SERMs,
      lasofoxifene diverts the receptor from its agonist-bound conformation by
      displacing the C-terminal AF-2 helix into the site at which the LXXLL motif of
      coactivator proteins would otherwise be able to bind. Lasofoxifene achieves this
      effect by occupying the space normally filled by residue Leu 540, as well as by
      modulating the conformation of residues of helix 11 (His 524, Leu 525). A well
      defined salt bridge between lasofoxifene and Asp 351 suggests that charge
      neutralization in this region of the receptor may explain the some of the
      antiestrogenic effects of lasofoxifene. The results suggest general features of
      ERalpha/SERM recognition, and add a new dimension to efforts to rationalize
      differences between the biological activity profiles exhibited by these important
      pharmacological agents.

PMID- 17456743
TI  - A simple algorithm locates beta-strands in the amyloid fibril core of alpha
      synuclein, Abeta, and tau using the amino acid sequence alone.
AB  - Fibrillar inclusions are a characteristic feature of the neuropathology found in
      the alpha-synucleinopathies such as Parkinson's disease, dementia with Lewy
      bodies, and multiple system atrophy. Familial forms of alpha-synucleinopathies
      have also been linked with missense mutations or gene multiplications that result
      in higher protein expression levels. In order to form these fibrils, the protein,
      alpha-synuclein (alpha-syn), must undergo a process of self-assembly in which its
      native state is converted from a disordered conformer into a beta-sheet-dominated
      form. Here, we have developed a novel polypeptide property calculator to locate
      and quantify relative propensities for beta-strand structure in the sequence of
      alpha-syn. The output of the algorithm, in the form of a simple x-y plot, was
      found to correlate very well with the location of the beta-sheet core in alpha
      syn fibrils. In particular, the plot features three peaks, the largest of which
      is completely absent for the nonfibrillogenic protein, beta-syn. We also report
      similar significant correlations for the Alzheimer's disease-related proteins,
      Abeta and tau. A substantial region of alpha-syn is capable [corrected] of
      converting from its disordered conformation into a long [corrected] alpha-helical
      protein. We have developed the aforementioned algorithm to locate and quantify
      the alpha-helical hydrophobic moment in the amino acid sequence of alpha-syn. As
      before, the output of the algorithm, in the form of a simple x-y plot, was found
      to correlate very well with the location of alpha-helical structure in membrane
      bilayer-associated alpha-syn.

PMID- 17456744
TI  - Expression of proteins with dimethylarginines in Escherichia coli for protein
      protein interaction studies.
AB  - Protein arginine methylation often modulates protein-protein interactions. To
      isolate a sufficient quantity of proteins enriched in methyl arginine(s) from
      natural sources for biochemical studies is laborious and difficult. We describe
      here an expression system that produces recombinant proteins that are enriched in
      omega-N(G),N(G)-asymmetry dimethylarginines. A yeast type I arginine
      methyltransferase gene (HMT1) is put on a plasmid under the control of the
      Escherichia coli methionine aminopeptidase promoter for constitutive expression.
      The protein targeted for post-translational modification is put on the same
      plasmid behind a T7 promoter for inducible expression of His(6)-tagged proteins.
      Sbp1p and Stm1p were used as model proteins to examine this expression system.
      The 13 arginines within the arginine-glycine-rich motif of Sbp1p and the RGG
      sequence near the C terminus of Stm1p were methylated. Unexpectedly, the arginine
      residue on the thrombin cleavage site (LVPRGS) of the fusion proteins can also be
      methylated by Hmt1p. Sbp1p and Sbp1p/hmt1 were covalently attached to solid
      supports for the isolation of interacting proteins. The results indicate that
      arginine methylation on Sbp1p exerts both positive and negative effects on
      protein-protein interaction.

PMID- 17456745
TI  - DDOMAIN: Dividing structures into domains using a normalized domain-domain
      interaction profile.
AB  - Dividing protein structures into domains is proven useful for more accurate
      structural and functional characterization of proteins. Here, we develop a
      method, called DDOMAIN, that divides structure into DOMAINs using a normalized
      contact-based domain-domain interaction profile. Results of DDOMAIN are compared
      to AUTHORS annotations (domain definitions are given by the authors who solved
      protein structures), as well as to popular SCOP and CATH annotations by human
      experts and automatic programs. DDOMAIN's automatic annotations are most
      consistent with the AUTHORS annotations (90% agreement in number of domains and
      88% agreement in both number of domains and at least 85% overlap in domain
      assignment of residues) if its three adjustable parameters are trained by the
      AUTHORS annotations. By comparison, the agreement is 83% (81% with at least 85%
      overlap criterion) between SCOP-trained DDOMAIN and SCOP annotations and 77%
      (73%) between CATH-trained DDOMAIN and CATH annotations. The agreement between
      DDOMAIN and AUTHORS annotations goes beyond single-domain proteins (97%, 82%, and
      56% for single-, two-, and three-domain proteins, respectively). For an "easy"
      data set of proteins whose CATH and SCOP annotations agree with each other in
      number of domains, the agreement is 90% (89%) between "easy-set"-trained DDOMAIN
      and CATH/SCOP annotations. The consistency between SCOP-trained DDOMAIN and SCOP
      annotations is superior to two other recently developed, SCOP-trained, automatic
      methods PDP (protein domain parser), and DomainParser 2. We also tested a simple
      consensus method made of PDP, DomainParser 2, and DDOMAIN and a different version
      of DDOMAIN based on a more sophisticated statistical energy function. The DDOMAIN
      server and its executable are available in the services section on
      http://sparks.informatics.iupui.edu.

PMID- 17456746
TI  - Inter-ring communication allows the GroEL chaperonin complex to distinguish
      between different substrates.
AB  - The productive folding of substrate proteins by the GroEL complex of Escherichia
      coli requires the activity of both the chaperonin rings. These heptameric rings
      were shown to regulate the chaperonins' affinity for substrates and co-chaperonin
      via inter-ring communications; however, the molecular details of the interactions
      are not well understood. We have investigated the effect of substrate binding on
      inter-ring communications of the chaperonin complex, both the double-ring GroEL
      as well as the single-ring SR1 chaperonin in complex with four different
      substrates by using mass spectrometry. This approach shows that whereas SR1 is
      unable to distinguish between Rubisco, gp23, gp5, and MDH, GroEL shows clear
      differences upon binding these substrates. The most distinctive binding behavior
      is observed for Rubisco, which only occupies one GroEL ring. Both bacteriophage
      capsid proteins (gp23 and gp5) as well as MDH are able to bind to the two GroEL
      rings simultaneously. Our data suggest that inter-ring communication allows the
      chaperonin complex to differentiate between substrates. Using collision induced
      dissociation in the gas phase, differences between the chaperonin(substrate)
      complexes are observed only when both rings are present. The data indicate that
      the size of the substrate is an important factor that determines the degree of
      stabilization of the chaperonin complex.

PMID- 17456747
TI  - Cell-free complements in vivo expression of the E. coli membrane proteome.
AB  - Reconstituted cell-free (CF) protein expression systems hold the promise of
      overcoming the traditional barriers associated with in vivo systems. This is
      particularly true for membrane proteins, which are often cytotoxic and due to the
      nature of the membrane, difficult to work with. To evaluate the potential of cell
      free expression, we cloned 120 membrane proteins from E. coli and compared their
      expression profiles in both an E. coli in vivo system and an E. coli-derived cell
      free system. Our results indicate CF is a more robust system and we were able to
      express 63% of the targets in CF, compared to 44% in vivo. To benchmark the
      quality of CF produced protein, five target membrane proteins were purified and
      their homogeneity assayed by gel filtration chromatography. Finally, to
      demonstrate the ease of amino acid labeling with CF, a novel membrane protein was
      substituted with selenomethionine, purified, and shown to have 100% incorporation
      of the unnatural amino acid. We conclude that CF is a novel, robust expression
      system capable of expressing more proteins than an in vivo system and suitable
      for production of membrane proteins at the milligram level.

PMID- 17456748
TI  - Structural context for protein N-glycosylation in bacteria: The structure of
      PEB3, an adhesin from Campylobacter jejuni.
AB  - Campylobacter jejuni is unusual among bacteria in possessing a eukaryotic-like
      system for N-linked protein glycosylation at Asn residues in sequons of the type
      Asp/Glu-Xaa-Asn-Xaa-Ser/Thr. However, little is known about the structural
      context of the glycosylated sequons, limiting the design of novel recombinant
      glycoproteins. To obtain more information on sequon structure, we have determined
      the crystal structure of the PEB3 (Cj0289c) dimer. PEB3 has the class II
      periplasmic-binding protein fold, with each monomer having two domains with a
      ligand-binding site containing citrate located between them, and overall
      resembles molybdate- and sulfate-binding proteins. The sequon around Asn90 is
      located within a surface-exposed loop joining two structural elements. The three
      key residues are well exposed on the surface; hence, they may be accessible to
      the PglB oligosaccharyltransferase in the folded state.

PMID- 17456749
TI  - A bacterial two-hybrid system based on the twin-arginine transporter pathway of
      E. coli.
AB  - We have developed a bacterial two-hybrid system for the detection of interacting
      proteins that capitalizes on the folding quality control mechanism of the Twin
      Arginine Transporter (Tat) pathway. The Tat export pathway is responsible for the
      membrane translocation of folded proteins, including proteins consisting of more
      than one polypeptide, only one of which contains a signal peptide ("hitchhiker
      export"). Here, one protein (bait) is expressed as a fusion to a Tat signal
      peptide, whereas the second protein (prey) is fused to a protein reporter that
      can confer a phenotype only after export into the bacterial periplasmic space.
      Since the prey-reporter fusion lacks a signal peptide, it can only be exported as
      a complex with the bait-signal peptide fusion that is capable of targeting the
      Tat translocon. Using maltose-binding protein as a reporter, clones expressing
      interacting proteins can be grown on maltose minimal media or on MacConkey
      plates. In addition, we introduce the use of the cysteine disulfide oxidase DsbA
      as a reporter. Export of a signal peptide-prey:bait-DsbA complex into the
      periplasm allows complementation of dsbA(-) mutants and restores the formation of
      active alkaline phosphatase, which in turn can be detected by a chromogenic
      assay.

PMID- 17456750
TI  - Pathophysiology of sepsis.
AB  - Sepsis remains a critical problem with significant morbidity and mortality even
      in the modern era of critical care management. Multiple derangements exist in
      sepsis involving several different organs and systems, although controversies
      exist over their individual contribution to the disease process. Septic patients
      have substantial, life-threatening alterations in their coagulation system, and
      currently, there is an approved therapy with a component of the coagulation
      system (activated protein C) to treat patients with severe sepsis. Previously, it
      was believed that sepsis merely represented an exaggerated, hyperinflammatory
      response with patients dying from inflammation-induced organ injury. More recent
      data indicate that substantial heterogeneity exists in septic patients'
      inflammatory response, with some appearing immuno-stimulated, whereas others
      appear suppressed. Cellular changes continue the theme of heterogeneity. Some
      cells work too well such as neutrophils that remain activated for an extended
      time. Other cellular changes become accelerated in a detrimental fashion
      including lymphocyte apoptosis. Metabolic changes are clearly present, requiring
      close and individualized monitoring. At this point in time, the literature richly
      illustrates that no single mediator/system/pathway/pathogen drives the
      pathophysiology of sepsis. This review will briefly discuss many of the important
      alterations that account for the pathophysiology of sepsis.

PMID- 17456751
TI  - Genetic pathways to primary and secondary glioblastoma.
AB  - Glioblastoma is the most frequent and most malignant human brain tumor. The
      prognosis remains very poor, with most patients dying within 1 year after
      diagnosis. Primary and secondary glioblastoma constitute distinct disease
      subtypes, affecting patients of different age and developing through different
      genetic pathways. The majority of cases (>90%) are primary glioblastomas that
      develop rapidly de novo, without clinical or histological evidence of a less
      malignant precursor lesion. They affect mainly the elderly and are genetically
      characterized by loss of heterozygosity 10q (70% of cases), EGFR amplification
      (36%), p16(INK4a) deletion (31%), and PTEN mutations (25%). Secondary
      glioblastomas develop through progression from low-grade diffuse astrocytoma or
      anaplastic astrocytoma and manifest in younger patients. In the pathway to
      secondary glioblastoma, TP53 mutations are the most frequent and earliest
      detectable genetic alteration, already present in 60% of precursor low-grade
      astrocytomas. The mutation pattern is characterized by frequent G:C-->A:T
      mutations at CpG sites. During progression to glioblastoma, additional mutations
      accumulate, including loss of heterozygosity 10q25-qter ( approximately 70%),
      which is the most frequent genetic alteration in both primary and secondary
      glioblastomas. Primary and secondary glioblastomas also differ significantly in
      their pattern of promoter methylation and in expression profiles at RNA and
      protein levels. This has significant implications, particularly for the
      development of novel, targeted therapies, as discussed in this review.

PMID- 17456752
TI  - Mig-7 linked to vasculogenic mimicry.

PMID- 17456753
TI  - Treating the lesions, not the disease.

PMID- 17456754
TI  - Inactivation of Smad5 in endothelial cells and smooth muscle cells demonstrates
      that Smad5 is required for cardiac homeostasis.
AB  - Smads are intracellular signaling proteins that transduce signals elicited by
      members of the transforming growth factor (TGF)-beta superfamily. Smad5 and Smad1
      are highly homologous, and they mediate primarily bone morphogenetic protein
      (Bmp) signals. We used the Cre-loxP system and Sm22-Cre and Tie-1-Cre mice to
      study the function of Smad5 in the developing blood vessel wall. Analysis of
      embryos demonstrated that deletion of Smad5 in endothelial or smooth muscle cells
      resulted in a normal organization of embryonic and extra-embryonic vasculature.
      Angiogenic assays performed in adult mice revealed that mutant mice display a
      comparable angiogenic and vascular remodeling response to control mice. In Sm22
      Cre; Smad5(fl/-) mice, Smad5 is also deleted in cardiomyocytes. Echocardiographic
      analysis on those 9-month-old female mice demonstrated larger left ventricle
      internal diameters and decreased fractional shortening compared with control
      littermates without signs of cardiac hypertrophy. The decreased cardiac
      contractility was associated with a decreased performance in a treadmill
      experiment. In isolated cardiomyocytes, fractional shortening was significantly
      reduced compared with control cells. These data demonstrate that restricted
      deletion of Smad5 in the blood vessel wall results in viable mice. However, loss
      of Smad5 in cardiomyocytes leads to a mild heart defect.

PMID- 17456755
TI  - Deficiency of endothelial nitric-oxide synthase confers susceptibility to
      diabetic nephropathy in nephropathy-resistant inbred mice.
AB  - Recent studies have implicated dysfunctional endothelial nitric-oxide synthase
      (eNOS) as a common pathogenic pathway in diabetic vascular complications.
      However, functional consequences are still incompletely understood. To determine
      the role of eNOS-derived nitric oxide (NO) in diabetic nephropathy, we induced
      diabetes in eNOS knockout (KO) and wild-type (WT) mice on the C57BL6 background,
      using low-dose streptozotocin injection, and we investigated their glomerular
      phenotype at up to 20 weeks of diabetes. Although the severity of hyperglycemia
      in diabetic eNOS KO mice was similar to diabetic WT mice, diabetic eNOS KO mice
      developed overt albuminuria, hypertension, and glomerular mesangiolysis, whereas
      diabetic WT and nondiabetic control mice did not. Glomerular hyperfiltration was
      also significantly reduced in diabetic eNOS KO mice. Electron micrographs from
      diabetic eNOS KO mice revealed an injured endothelial morphology, thickened
      glomerular basement membrane, and focal foot process effacement. Furthermore, the
      anionic sites at glomerular endothelial barrier estimated by cationic ferritin
      binding were reduced in diabetic eNOS KO mice. In aggregate, these results
      demonstrate that deficiency of eNOS-derived NO causes glomerular endothelial
      injury in the setting of diabetes and results in overt albuminuria and glomerular
      mesangiolysis in nephropathy-resistant inbred mice. The findings indicate a vital
      role for eNOS-derived NO in the pathogenesis of diabetic nephropathy.

PMID- 17456756
TI  - Inhibition of CXCL16 attenuates inflammatory and progressive phases of anti
      glomerular basement membrane antibody-associated glomerulonephritis.
AB  - Chemokines recruit and activate leukocytes during inflammation. CXCL16 is a
      recently discovered chemokine that is expressed as a transmembrane protein that
      is cleaved to form the active, soluble chemokine. We analyzed the role of CXCL16
      in the development of inflammation and in the progression of the anti-glomerular
      basement membrane (GBM) antibody-induced experimental glomerulonephritis in
      Wistar-Kyoto rats. CXCL16 was expressed in glomerular endothelial cells and
      mediated adhesion of macrophages expressing CXCL16 and its cognate receptor,
      CXCR6. Glomerular infiltrates displayed a strong migratory response to soluble
      CXCL16. Soluble CXCL16 and its receptor CXCR6 were induced in nephritic glomeruli
      throughout the disease, and CXCL16 expression correlated with the up-regulation
      of ADAM10, suggesting that this disintegrin and metalloproteinase mediates the
      chemokine activity of CXCL16. Blocking CXCL16 in the acute inflammatory phase or
      progressive phase of established glomerulonephritis significantly attenuated
      monocyte/macrophage infiltration and glomerular injury; proteinuria also
      improved. We conclude that CXCL16/CXCR6 plays a critical role in stimulating
      leukocyte influx, which causes glomerular damage during anti-GBM
      glomerulonephritis. Blocking CXCL16 actions limits the progression of anti-GBM
      glomerulonephritis even when the disease is established.

PMID- 17456757
TI  - Intrapulmonary delivery of ricin at high dosage triggers a systemic inflammatory
      response and glomerular damage.
AB  - In view of the possibility that ricin may be used as a bioweapon against human
      populations, we examined the pathological consequences that occur in mice after
      introduction of ricin into the pulmonary system. Intratracheal instillation of a
      lethal dose of ricin (20 microg/100 g body weight) resulted in a hemorrhagic
      inflammatory response in multiple organs, accompanied by activation of mitogen
      activated protein kinases, increased synthesis of proinflammatory RNA
      transcripts, and increased levels of circulating cytokines and chemokines. A
      sublethal dose of instilled ricin (2 microg/100 g body weight) induced a similar
      response in lungs but did not cause detectable damage in other organs. Lungs of
      mice that recovered from a sublethal dose of ricin displayed evidence of fibrosis
      and residual damage. A lethal dose of ricin caused accumulation of
      proinflammatory RNA transcripts and substantial damage to 28S rRNA of multiple
      organs, including lung, kidney, spleen, liver, and blood, demonstrating that
      instilled ricin gained access to the circulation. The kidneys of mice instilled
      with a lethal dose of ricin showed accumulation of fibrin/fibrinogen in
      glomerular capillaries, increased numbers of glomerular leukocytes, and
      impairment of kidney function. A sublethal dose of ricin failed to induce damage
      to 28S rRNA in kidney or other extrapulmonary organs.

PMID- 17456758
TI  - Nuclear factor-kappa B, p38, and stress-activated protein kinase mitogen
      activated protein kinase signaling pathways regulate proinflammatory cytokines
      and apoptosis in human placental explants in response to oxidative stress:
      effects of antioxidant vitamins.
AB  - Preeclampsia is a potentially fatal complication of human pregnancy characterized
      by hypertension, proteinuria, and edema. Placental oxidative stress is a key
      element in the pathogenesis of the syndrome and results in the release of a
      cocktail of factors, including proinflammatory cytokines and apoptotic debris,
      that in turn cause activation of the maternal endothelium. The intermediary
      molecular mechanisms underlying this release are unknown, but they represent a
      potential target for therapeutic interventions. We examined activation of
      signaling pathways during hypoxia-reoxygenation of villous explants in vitro.
      Hypoxia-reoxygenation activated the p38 and stress-activated protein kinase
      mitogen-activated protein kinase (MAPK) and the nuclear factor-kappaB pathways.
      Downstream consequences included increased tissue concentrations and secretion of
      tumor necrosis factor-alpha and interleukin-1 beta, increased expression of
      cyclooxygenase-2, and increased apoptosis. Administration of vitamins C and E to
      explants blocked activation of the p38 and stress-activated protein kinase MAPK
      and nuclear factor-kappaB pathways. Vitamin administration or p38 pathway
      inhibition also reduced cyclooxygenase-2 expression, tumor necrosis factor-alpha
      and interleukin-1 beta secretion, and the levels of apoptosis. We conclude that
      oxidative stress is a potent inducer of placental synthesis and release of
      proinflammatory factors. Most of these effects are mediated through the p38 MAPK
      and nuclear factor-kappaB pathways and can be effectively blocked by vitamins C
      and E in vitro.

PMID- 17456759
TI  - Induction of apoptosis by crambene protects mice against acute pancreatitis via
      anti-inflammatory pathways.
AB  - Apoptosis is a teleologically beneficial form of cell death in acute
      pancreatitis. Our previous work has demonstrated that induction of pancreatic
      acinar cell apoptosis by crambene protects mice against acute pancreatitis.
      However, little is known about how the induction of apoptosis reduces the
      severity of acute pancreatitis. Because the clearance of apoptotic cells might
      suppress inflammation and critically regulate immune responses, we postulate that
      clearance of apoptotic cells stimulates an anti-inflammatory response, which has
      a protective action against acute pancreatitis. To test this hypothesis,
      induction of apoptosis in acute pancreatitis in vivo and co-cultures of
      peritoneal resident macrophages with apoptotic acinar cells in vitro were used as
      experimental systems, testing expression of phagocytic receptors and levels of
      inflammatory mediators. Moreover, neutralizing anti-interleukin (IL)-10
      monoclonal antibody (2.5 mg/kg) was used before the induction of apoptosis in
      acute pancreatitis, testing whether the protection from apoptosis induction would
      be removed. Our study showed that clearance of apoptotic acinar cells, which may
      occur essentially through the CD36-positive macrophage, stimulates the release of
      anti-inflammatory mediators like IL-10. IL-10 plays an important role in crambene
      induced protection in acute pancreatitis. Thus, induction of pancreatic acinar
      cell apoptosis by crambene protects mice against acute pancreatitis via induction
      of anti-inflammatory pathways.

PMID- 17456760
TI  - Loss of fibulin-2 expression is associated with breast cancer progression.
AB  - Fibulin-2, an extracellular matrix protein expressed by normal epithelia, was
      found to be down-regulated in several breast cancer cell lines. Fibulin-2 protein
      expression was also decreased in breast cancer tissue samples as evaluated by
      immunohistochemistry. Reintroduction of Fibulin-2 into breast cancer cell lines
      that do not express Fibulin-2 reduced cancer cell motility and invasion in vitro
      but had no effect on cell growth and adhesion properties. Together with evidence
      that Fibulin-2 contributes to wound healing and inhibits smooth muscle cell
      migration, our findings suggest that loss of Fibulin-2 expression may facilitate
      migration and invasion in breast cancer.

PMID- 17456761
TI  - Direct involvement of breast tumor fibroblasts in the modulation of tamoxifen
      sensitivity.
AB  - Using contact-dependent three-dimensional coculture systems and serum-free
      conditions, we compared the ability of estrogen receptor (ER)-alpha(+) tamoxifen
      sensitive premalignant (EIII8) or tumorigenic (MCF-7), ER-alpha(+) tamoxifen
      resistant (EIII8-TAM(R)) or ER-alpha(-) MDA-MB-231 breast cancer cells to
      interact and undergo epithelial morphogenesis on association with breast tumor
      derived fibroblasts. Although all breast cancer cell lines interacted with tumor
      fibroblasts, EIII8 and its intrinsically tamoxifen-resistant counterpart EIII8
      TAM(R) cells were most receptive and responded with dramatic, albeit, aberrant
      epithelial morphogenesis. EIII8 cells underwent epithelial morphogenesis when
      cocultured with fibroblasts from ER-alpha(-)/PgR(-) or ER-alpha(+)/PgR(+) breast
      tumors; however, EIII8 cells cocultured with ER-alpha(-)/PgR(-) tumor-derived
      fibroblasts exhibited decreased tamoxifen sensitivity compared with cells
      cocultured with ER-alpha(+)/PgR(+) tumor fibroblasts. Fibroblast-induced
      tamoxifen resistance was accompanied by mitogen-activated protein kinase and Akt
      hyperactivation, reduced sensitivity to U0126 or LY294002, and ER-alpha
      hyperphosphorylation in the activation function-1 domain. The intrinsic tamoxifen
      resistance of EIII8-Tam(R) cells correlated with constitutive ER-alpha
      hyperphosphorylation that was unaffected by the tumor fibroblasts. Our results
      suggest that tumor fibroblast-induced tamoxifen resistance of EIII8 cells is not
      mediated by epidermal growth factor receptor or insulin-like growth factor (IGF)
      1R axes because no correlation was found between expression levels of IGF-1, IGF
      2, phosphorylated IGF-1R, or epidermal growth factor receptor, and tamoxifen
      sensitivity of EIII8 fibroblast cultures.

PMID- 17456762
TI  - Luteogenic hormones act through a vascular endothelial growth factor-dependent
      mechanism to up-regulate alpha 5 beta 1 and alpha v beta 3 integrins, promoting
      the migration and survival of human luteinized granulosa cells.
AB  - The formation of the corpus luteum (CL) is critical for the establishment of a
      successful pregnancy. After ovulation, the CL develops from the remnants of the
      ovulated ovarian follicle. This process, which involves varying cell-matrix
      interactions, is poorly characterized. To understand the role and potential
      regulation of cell-matrix interactions in the formation of the CL, we
      investigated the expression and activity of the matrix protein fibronectin (FN)
      and several of its integrin receptors on luteinized granulosa cells (GCs). In
      situ, FN and several FN-binding integrins were detected around luteinizing GCs
      during the early luteal phase, although expression declined in the late luteal
      phase. In vitro, GCs released FN, and stimulation of these cells with human
      chorionic gonadotropin increased the surface expression of FN, alpha(5)beta(1),
      and alpha(v)beta(3). Up-regulation of these proteins on GCs was reproduced by
      stimulation with vascular endothelial growth factor (VEGF) and was inhibited by
      anti-VEGF antibody. Lastly, expression of alpha(5)beta(1) and alpha(v)beta(3)
      mediated adhesion to FN, facilitated migration, and prevented apoptosis. These
      data suggest that in vivo luteogenic hormones, in part through a VEGF-dependent
      mechanism, stimulate selected integrin-matrix adhesive interactions that promote
      the motility and survival of GCs and thus contribute to the formation and
      preservation of the CL.

PMID- 17456763
TI  - Tissue plasminogen activator induces pancreatic cancer cell proliferation by a
      non-catalytic mechanism that requires extracellular signal-regulated kinase 1/2
      activation through epidermal growth factor receptor and annexin A2.
AB  - Tissue plasminogen activator (tPA) is overexpressed in pancreatic ductal
      carcinoma and is involved in tumor progression. This effect is probably mediated
      through the activation of angiogenesis, cell invasion, and cell proliferation.
      Previous studies support the notion that the effects of tPA on cell invasion
      require its proteolytic activity. Here, we report the molecular mechanism
      responsible for the proliferative effects of tPA on pancreatic tumor cells. tPA
      activates the extracellular signal-regulated kinase 1/2 signaling pathway in a
      manner that is independent of its catalytic activity. We also show that at least
      two membrane receptors, epidermal growth factor receptor and annexin A2, which
      are overexpressed in pancreatic cancer, are involved in the transduction of tPA
      signaling in pancreatic tumors. This observation suggests the establishment of an
      amplification loop in tumor cell proliferation. Double immunofluorescence
      experiments showed co-localization of tPA/epidermal growth factor receptor and
      tPA/annexin A2 in pancreas cancer cells. These results add novel insights into
      the non-catalytic functions of tPA in cancer and the molecular mechanisms behind
      the effects of this protease on cell proliferation, including a role for
      epidermal growth factor receptor.

PMID- 17456764
TI  - Retinoblastoma pathway dysregulation causes DNA methyltransferase 1
      overexpression in cancer via MAD2-mediated inhibition of the anaphase-promoting
      complex.
AB  - We have examined the mechanism of normal DNA methyltransferase 1 (DNMT1)
      degradation as well as its mechanism of dysregulation in cancer. We have
      previously reported that DNMT1 protein levels were elevated and abnormally
      stabilized because of defective degradation through its N-terminal destruction
      domain. Here, we report that DNMT1 was abnormally stabilized in several cancer
      cell lines and that, in cells with normal DNMT1 destruction, depletion of CDC20
      or FZR1 (two substrate recognition adaptor components of the anaphase-promoting
      complex) resulted in stabilization of DNMT1 that was partially dependent on the N
      terminal destruction domain, thus implicating this cell cycle regulator in the
      destruction of DNMT1. MAD2, an inhibitor of CDC20, was shown to stabilize DNMT1
      levels, and overexpression of MAD2, a consequence of retinoblastoma (RB) pathway
      dysregulation, was shown to correlate with impaired G(1) phase DNMT1 destruction
      and RB inactivation by hyperphosphorylation in several normal and cancer cell
      lines. Furthermore, in a series of 85 cases of human breast cancer, a moderately
      strong, but highly significant, correlation between MAD2 and DNMT1
      immunohistochemical staining was observed, yielding a Spearman rank order
      correlation coefficient of 0.37 (P<0.001). This suggests that RB pathway
      inactivation, a common dysfunction in cancer cells, may be the underlying cause
      of DNMT1 dysregulation.

PMID- 17456765
TI  - A homeobox gene related to Drosophila distal-less promotes ovarian tumorigenicity
      by inducing expression of vascular endothelial growth factor and fibroblast
      growth factor-2.
AB  - Homeobox genes control developmental patterning and are increasingly being found
      to be deregulated in tumors. The DLX4 homeobox gene maps to the 17q21.3-q22
      region that is amplified in some epithelial ovarian cancers. Because
      amplification of this region correlates with poor prognosis, we investigated
      whether DLX4 overexpression contributes to aggressive behavior of this disease.
      DLX4 was not detected in normal ovary and cystadenomas, whereas its expression in
      ovarian carcinomas was strongly associated with high tumor grade and advanced
      disease stage. Overexpression of DLX4 in ovarian cancer cells promoted growth in
      low serum and colony formation. Imaging of mice bearing intraperitoneal tumors
      revealed that DLX4 overexpression substantially increased tumor burden. Tumors
      that overexpressed DLX4 were more vascularized than vector-control tumors.
      Conditioned medium of DLX4-overexpressing tumor cells was more effective than
      medium conditioned by vector-control cells in stimulating endothelial cell
      growth. These observations were associated with the ability of DLX4 to induce
      expression of vascular endothelial growth factor as well as intracellular and
      secreted isoforms of fibroblast growth factor-2. Moreover, increased levels of
      these fibroblast growth factor-2 isoforms induced vascular endothelial growth
      factor expression in tumor cells. This study reveals a novel role for a homeobox
      gene in ovarian tumorigenicity by its induction of a proangiogenic, growth
      stimulatory molecular program.

PMID- 17456766
TI  - Epstein-Barr virus (EBV) latent membrane protein-1 down-regulates tumor necrosis
      factor-alpha (TNF-alpha) receptor-1 and confers resistance to TNF-alpha-induced
      apoptosis in T cells: implication for the progression to T-cell lymphoma in EBV
      associated hemophagocytic syndrome.
AB  - The infection of T cells by Epstein-Barr virus (EBV) may result in hemophagocytic
      syndrome (HPS) through enhanced cytokine secretion, particularly tumor necrosis
      factor-alpha (TNF-alpha), by EBV latent membrane protein-1 (LMP-1). One
      bewildering observation of HPS patients is relapsing disease or progression to T
      cell lymphoma. This finding raises the question whether EBV LMP-1-expressing T
      cells may survive and proliferate in the cytokine milieu of HPS. To explore this
      possibility, we tested the sensitivity of LMP-1-expressing T cells to apoptosis
      in the presence of TNF-alpha. LMP-1 up-regulated TNF-alpha through TRAF2,5 and
      nuclear factor-kappaB pathway in T cells. The LMP-1-expressing T cells then
      became resistant to TNF-alpha-induced apoptosis. Interestingly, the expression of
      TNFR1 was remarkably down-regulated by LMP-1 in T cells. Furthermore, the TNF
      alpha/TNFR1 downstream death signal TNFR1-associated death domain protein was
      constitutively recruited by LMP-1, and the activities of apoptotic caspases 3, 8,
      and 9 were suppressed. Reconstitution of TNFR1 successfully reversed the TNF
      alpha-induced apoptotic cascades. Therefore, EBV LMP-1 not only activates T cells
      to proliferate but also confers resistance to TNF-alpha-mediated apoptosis via
      down-regulation of TNFR1 in the cytokine milieu of HPS. This finding provides a
      potential mechanism to explain the disease persistence or progression to T-cell
      lymphoma in HPS patients.

PMID- 17456767
TI  - Epigenetic silencing through DNA and histone methylation of fibroblast growth
      factor receptor 2 in neoplastic pituitary cells.
AB  - Four members of the fibroblast growth factor receptor (FGFR) family of tyrosine
      kinases transduce signals of a diverse group of more than 23 fibroblast growth
      factor (FGF) ligands. Each prototypic receptor is composed of three
      immunoglobulin-like extracellular domains, two of which are involved in ligand
      binding. Alternative RNA splicing of one of two exons results in two different
      forms of the second half of the third immunoglobulin-like domain, the IIIb or
      IIIc isoforms. The contribution of each receptor and their isoforms in
      tumorigenesis remains unknown. In the pituitary, FGFR2 is expressed primarily as
      the IIIb isoform in normal adenohypophysial cells. In contrast, FGFR2 is
      significantly down-regulated in mouse corticotroph AtT20 tumor cells where the 5'
      promoter is methylated. Treatment of AtT20 cells with 5'-azacytidine resulted in
      FGFR2 re-expression, mainly as the FGFR2-IIIb isoform. Chromatin
      immunoprecipitation revealed evidence of histone methylation, but not of
      deacetylation, in the silencing of FGFR2 in AtT20 cells. Exposure of these cells
      to the cognate FGFR2-IIIb ligand FGF-7 resulted in diminished Rb phosphorylation
      and accumulation of p21 and p27, indicating diminished cell cycle progression.
      Examination of primary human pituitary adenomas revealed FGFR2 down-regulation in
      52% (11 of 21) of samples and FGFR2 promoter DNA methylation in 45% (10 of 22) of
      samples. These data highlight the contribution from DNA and histone methylation
      as epigenetic mechanisms responsible for FGFR2 silencing in pituitary neoplasia.

PMID- 17456768
TI  - Emergence of anti-red blood cell antibodies triggers red cell phagocytosis by
      activated macrophages in a rabbit model of Epstein-Barr virus-associated
      hemophagocytic syndrome.
AB  - Hemophagocytic syndrome (HPS) is a fatal complication frequently associated with
      viral infections. In childhood HPS, Epstein-Barr virus (EBV) is the major
      causative agent, and red blood cells (RBCs) are predominantly phagocytosed by
      macrophages. To investigate the mechanism of RBC phagocytosis triggered by EBV
      infection, we adopted a rabbit model of EBV-associated HPS previously established
      by using Herpesvirus papio (HVP). The kinetics of virus-host interaction was
      studied. Using flow cytometry, we detected the emergence of antibody-coated RBCs,
      as well as anti-platelet antibodies, at peak virus load period at weeks 3 to 4
      after HVP injection, and the titers increased thereafter. The presence of anti
      RBCs preceded RBC phagocytosis in tissues and predicted the full-blown
      development of HPS. The anti-RBC antibodies showed cross-reactivity with Paul
      Bunnell heterophile antibodies. Preabsorption of the HVP-infected serum with
      control RBCs removed the majority of anti-RBC activities and remarkably reduced
      RBC phagocytosis. The RBC phagocytosis was specifically mediated via an Fc
      fragment of antibodies in the presence of macrophage activation. Therefore, the
      emergence of anti-RBC antibodies and the presence of macrophage activation are
      both essential in the development of HPS. Our observations in this animal model
      provide a potential mechanism for hemophagocytosis in EBV infection.

PMID- 17456769
TI  - Murine cerebral malaria development is independent of toll-like receptor
      signaling.
AB  - Malaria pigment hemozoin was reported to activate the innate immunity by Toll
      like receptor (TLR)-9 engagement. However, the role of TLR activation for the
      development of cerebral malaria (CM), a lethal complication of malaria infection
      in humans, is unknown. Using Plasmodium berghei ANKA (PbA) infection in mice as a
      model of CM, we report here that TLR9-deficient mice are not protected from CM.
      To exclude the role of other members of the TLR family in PbA recognition, we
      infected mice deficient for single TLR1, -2, -3, -4, -6, -7, or -9 and their
      adapter proteins MyD88, TIRAP, and TRIF. In contrast to lymphotoxin alpha
      deficient mice, which are resistant to CM, all TLR-deficient mice were as
      sensitive to fatal CM development as wild-type control mice and developed typical
      microvascular damage with vascular leak and hemorrhage in the brain and lung,
      together with comparable parasitemia, thrombocytopenia, neutrophilia, and
      lymphopenia. In conclusion, the present data do not exclude the possibility that
      malarial molecular motifs may activate the innate immune system. However, TLR
      dependent activation of innate immunity is unlikely to contribute significantly
      to the proinflammatory response to PbA infection and the development of fatal CM.

PMID- 17456770
TI  - Phase-dependent roles of E-selectin during chronic contact hypersensitivity
      responses.
AB  - Chronic contact hypersensitivity (CH) models induced by repeated hapten exposure
      exhibit chronic dermatitis and immunological abnormalities resembling atopic
      dermatitis. To assess the contribution of endothelial selectins (P- and E
      selectins) to cutaneous chronic inflammation, chronic CH responses were assessed
      in mice lacking P- or E-selectin. Elicitation with oxazolone on the ears of P
      selectin(-/-) mice 7 days after the sensitization induced a typical delayed-type
      hypersensitivity response similar to that found in wild-type mice. By contrast, a
      significant increase in ear swelling was observed in E-selectin(-/-) mice 36 to
      48 hours after first elicitation. E-selectin(-/-) mice showed augmented P
      selectin up-regulation, and administration of anti-P-selectin monoclonal antibody
      significantly inhibited the enhanced ear response, suggesting that the enhanced
      ear-swelling response in E-selectin(-/-) mice resulted from compensatory increase
      in P-selectin expression. In the late phase of chronic CH, acceleration of ear
      swelling was significantly reduced in both E- and P-selectin(-/-) mice relative
      to wild-type littermates. Thus, the loss of P- or E-selectin suppressed
      inflammatory responses during the chronic phase of the chronic models, whereas
      early-phase inflammatory responses were exacerbated by E-selectin blockade.
      Collectively, P- and E-selectins cooperatively regulate CH response, although
      their roles may be different depending on the phase of the reaction.

PMID- 17456771
TI  - Expression of the murine Pomt1 gene in both the developing brain and adult muscle
      tissues and its relationship with clinical aspects of Walker-Warburg syndrome.
AB  - Walker-Warburg syndrome (WWS) is the most severe of a group of congenital
      disorders that have in common defects in the O-glycosylation of alpha
      dystroglycan. WWS is characterized by congenital muscular dystrophy coupled with
      severe ocular and brain malformations. Moreover, in at least one-fifth of the
      reported cases, mutations in the POMT1 gene are responsible for this disease.
      During embryonic development (E8.5 to E11.5), the mouse Pomt1 gene is expressed
      in the tissues most severely affected in WWS, the muscle, eye, and brain. In this
      study, we show that mPomt1 expression is maintained in the muscle and eye in
      later developmental stages and, notably, that its expression is particularly
      strong in regions of brain and cerebellum that, when affected, could generate the
      defects observed in patients with WWS. We show that the Pomt1 protein is
      localized to the sarcoplasmic reticulum of muscle tissue cells in adult mice,
      where alpha-dystroglycan is O-glycosylated. Furthermore, the Pomt1 protein is
      localized to the acrosome of maturing spermatids, where alpha-dystroglycan is not
      glycosylated, so that Pomt1 might have a different target for O-mannosylation in
      the testes. This expression pattern in the testes could also be related to the
      gonadal anomalies observed in some patients with WWS.

PMID- 17456772
TI  - Lithium reduces tau phosphorylation but not A beta or working memory deficits in
      a transgenic model with both plaques and tangles.
AB  - Glycogen synthase kinase 3 (GSK-3) is a major kinase implicated in the
      pathogenesis of Alzheimer's disease (AD), and reducing its activity may have
      therapeutic efficacy. Two variants exist, referred to as GSK-3 alpha and GSK
      3beta. In addition to the latter's well-described role in the phosphorylation of
      tau, reports also suggest that GSK-3 alpha may regulate amyloid precursor protein
      processing and Abeta formation. The activities of both GSK-3 alpha and GSK-3beta
      are reduced by lithium, a well-tolerated drug used in humans to combat bipolar
      disorder. Here, we investigate the therapeutic efficacy of chronic lithium
      administration in aged 3xTg-AD mice that harbor both plaques and tangles. We
      found that lithium reduced tau phosphorylation but did not significantly alter
      the A beta load. Despite the reduction in phosphotau, lithium treatment did not
      improve deficits in working memory. Although other studies have investigated the
      effects of lithium on tau biochemistry, this study represents the first to
      address comprehensively its therapeutic potential on other critical aspects of AD
      including its effect on A beta and learning and memory. It remains to be
      determined from human clinical trials whether lithium treatment alone will
      improve the clinical outcome in AD patients. These results, however, suggest that
      the most efficacious treatment will be combining lithium with other anti-A beta
      interventions.

PMID- 17456773
TI  - Overexpression of the transcriptional factor Runx2 in osteoblasts abolishes the
      anabolic effect of parathyroid hormone in vivo.
AB  - There is convincing evidence that Runx2 could be a regulator of the anabolic
      action of parathyroid hormone (PTH) in bone. We therefore decided to determine
      how Runx2 overexpression in osteoblasts affects the anabolic response to PTH.
      Transgenic osteoporotic female mice overexpressing Runx2 (TG) and their wild-type
      littermates (WT) were treated with PTH (100 microg/kg/day, 7 days a week) or with
      the vehicle for 6 weeks. Unexpectedly, Runx2 overexpression blunted the increase
      in the mineral density and volume of bone induced by intermittent PTH in WT mice.
      Our findings also indicate that PTH failed to increase bone formation in TG mice
      overexpressing Runx2. This abolition of the effect of PTH by Runx2 overexpression
      was attributable to a decrease in the differentiation of osteoblastic cells both
      in vivo and in vitro. Finally, we showed that less cAMP was induced by PTH and
      that there were fewer PTH binding sites in TG than WT osteoblasts. In conclusion,
      our findings demonstrate that in vivo a high level of Runx2 abolishes the
      anabolic effect of PTH, probably via a decrease in the sensitivity of TG
      osteoblasts to PTH, and that the level of expression of Runx2 is critical if PTH
      is to produce its anabolic effect on bone in vivo.

PMID- 17456774
TI  - Inhibition of notch signaling induces neural differentiation in Ewing sarcoma.
AB  - Cells from Ewing sarcoma exhibit cellular features and express markers,
      suggesting that the tumor is of neuroectodermal origin. Because Notch signaling
      regulates the differentiation of neuroectodermal cells during development, we
      examined the role of Notch signaling in Ewing sarcomas. We found that Ewing
      sarcomas express Notch receptors, ligands, and the Notch target gene HES1. To
      determine the functional implications of Notch signaling, we expressed
      tetracycline-regulated constitutively active, dominant-negative (DN), or wild
      type Notch-1 receptors in two Ewing sarcoma cell lines, or we treated the cell
      lines with a gamma-secretase inhibitor. Expression of the constitutively active
      Notch-1 reduced proliferation and expression of the DN Notch-1 reduced apoptosis
      in vitro. However, there was only a small difference in the volume of tumors that
      formed when the cell lines expressing these constructs were implanted in nude
      mice. Xenograft tumors derived from the cell lines expressing DN Notch-1
      exhibited a neural phenotype. Treatment with a gamma-secretase inhibitor caused
      similar changes as expression of the DN construct. Notch signaling plays a role
      in cell differentiation, proliferation, and apoptosis in Ewing sarcoma, but its
      inhibition is only associated with a small change in tumor growth potential.

PMID- 17456775
TI  - Elevated neuronal expression of CD200 protects Wlds mice from inflammation
      mediated neurodegeneration.
AB  - Axonal damage secondary to inflammation is likely the substrate of chronic
      disability in multiple sclerosis and is found in the animal model of experimental
      autoimmune encephalomyelitis (EAE). Wld(s) mice have a triplication of the fusion
      gene Ube4b/Nmnat and a phenotype of axon protection. Wld(s) mice develop an
      attenuated disease course of EAE, with decreased demyelination, reduced axonal
      pathology, and decreased central nervous system (CNS) macrophage and microglial
      accumulation. We show that attenuated disease in Wld(s) mice was associated with
      robust constitutive expression of the nonsignaling CD200 molecule on neurons in
      the CNS compared with control mice. CD200 interacts with its signaling receptor
      CD200R, which we found to be expressed on microglia, astrocytes, and
      oligodendrocytes at similar levels in control and Wld(s) mice. Administration of
      blocking anti-CD200 antibody to Wld(s) mice abrogated disease attenuation and was
      associated with increased CNS inflammation and neurodegeneration. In vitro,
      Wld(s) neuronal cultures were protected from microglial-induced neurotoxicity
      compared with control cultures, but protection was abrogated by anti-CD200
      antibody. The CD200-CD200R pathway plays a critical role in attenuating EAE and
      reducing inflammation-mediated damage in the CNS. Strategies that up-regulate the
      expression of CD200 in the CNS or molecules that ligate the CD200R may be
      relevant as neuroprotective strategies in multiple sclerosis.

PMID- 17456776
TI  - Microglial recruitment, activation, and proliferation in response to primary
      demyelination.
AB  - We have characterized the cellular response to demyelination/remyelination in the
      central nervous system using the toxin cuprizone, which causes reproducible
      demyelination in the corpus callosum. Microglia were distinguished from
      macrophages by relative CD45 expression (CD45(dim)) using flow cytometry. Their
      expansion occurred rapidly and substantially outnumbered infiltrating macrophages
      and T cells throughout the course of cuprizone treatment. We used
      bromodeoxyuridine incorporation and bone marrow chimeras to show that both
      proliferation and immigration from blood accounted for increased microglial
      numbers. Microglia adopted an activated phenotype during demyelination, up
      regulating major histocompatibility class I and B7.2/CD86. A subpopulation of
      CD45(dim-high) microglia that expressed reduced levels of CD11b emerged during
      demyelination. These microglia expressed CD11c and were potent antigen-presenting
      cells in vitro. T cells were recruited to the demyelinated corpus callosum but
      did not appear to be activated. Our study highlights the role of microglia as a
      heterogeneous population of cells in primary demyelination, with the capacity to
      present antigen, proliferate, and migrate into demyelinated areas.

PMID- 17456777
TI  - Calpain-cleavage of alpha-synuclein: connecting proteolytic processing to disease
      linked aggregation.
AB  - Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are both
      characterized pathologically by the presence of neuronal inclusions termed Lewy
      bodies (LBs). A common feature found in LBs are aggregates of alpha-synuclein
      (alpha-Syn), and although it is now recognized that alpha-Syn is the major
      building block for these toxic filaments, the mechanism of how this occurs
      remains unknown. In the present study, we demonstrate that proteolytic processing
      of alpha-Syn by the protease calpain I leads to the formation of aggregated high
      molecular weight species and adoption of a beta-sheet structure. To determine
      whether calpain-cleavage of alpha-Syn occurs in PD and DLB, we designed site
      directed calpain-cleavage antibodies to alpha-Syn and tested their utility in
      several animal model systems. Detection of calpain-cleaved alpha-Syn was evident
      in mouse models of cerebral ischemia and PD and in a Drosophila model of PD. In
      the human PD and DLB brain, calpain-cleaved alpha-Syn antibodies immunolabeled
      LBs and neurites in the substantia nigra. Moreover, calpain-cleaved alpha-Syn
      fragments identified within LBs colocalized with activated calpain in neurons of
      the PD and DLB brains. These findings suggest that calpain I may participate in
      the disease-linked aggregation of alpha-Syn in various alpha-synucleinopathies.

PMID- 17456778
TI  - Epigenetic reversion of breast carcinoma phenotype is accompanied by changes in
      DNA sequestration as measured by AluI restriction enzyme.
AB  - The importance of microenvironment and context in regulation of tissue-specific
      genes is well established. DNA exposure to or the sequestration from nucleases
      detects differences in higher order chromatin structure in intact cells without
      disturbing cellular or tissue architecture. To investigate the relationship
      between chromatin organization and tumor phenotype, we used an established three
      dimensional assay in which normal and malignant human breast cells can be easily
      distinguished by the morphology of the structures they make (acinus-like versus
      tumor-like, respectively). We show that these phenotypes can be distinguished
      also by sensitivity to AluI digestion in which the malignant cells resist
      digestion relative to nonmalignant cells. Treatment of T4-2 breast cancer cells
      in three-dimensional culture with cAMP analogs or a phosphatidylinositol 3-kinase
      inhibitor not only reverted their phenotype from nonpolar to polar acinar-like
      structures but also enhanced chromatin sensitivity to AluI. By using different
      cAMP analogs, we show that cAMP-induced phenotypic reversion, polarization, and
      shift in DNA organization act through a cAMP-dependent protein-kinase A-coupled
      signaling pathway. Importantly, inhibitory antibody to fibronectin produced the
      same effect. These experiments underscore the concept that modifying the tumor
      microenvironment can alter the organization of tumor cells and demonstrate that
      architecture and global chromatin organization are coupled and highly plastic.

PMID- 17456779
TI  - Histological and culture studies with respect to ABCG2 expression support the
      existence of a cancer cell hierarchy in human hepatocellular carcinoma.
AB  - In this study, we examined the possible involvement of progenitor cells in the
      carcinogenesis of human hepatocellular carcinoma (HCC) using tissue specimens and
      cell lines. We used ATP-binding cassette transporter ABCG2 as a progenitor cell
      marker. Immunohistochemically, ABCG2(+) hepatocytes were observed in the
      periportal areas of the dysplastic nodule, and ABCG2(+) cancer cells were also
      scattered or focally clustered in HCC. We sorted the cultured HCC cells (HuH7 and
      PLC5) into ABCG2(+) and ABCG2(-) subpopulations and then subcultured them for 4
      weeks. ABCG2(+) cells could generate ABCG2(+) and ABCG2(-) progenies during
      subculture, whereas ABCG2(-) cells bore only ABCG2(-) cells, suggesting that a
      cancer cell hierarchy with reference to ABCG2 exists in HCC cells and that
      ABCG2(+) cells reside at the higher rank in that hierarchy. Interestingly, other
      progenitor cell markers including cytokeratin 19 and alpha-fetoprotein were
      mainly expressed in ABCG2(+) subpopulations. Conversely, albumin expression was
      more intense in ABCG2(-) cells. In addition, the expression patterns of
      transcription factors (GATA6, CCAAT/enhancer-binding protein alpha, and
      CCAAT/enhancer-binding protein beta) in ABCG2(+) and ABCG2(-) cells resembled
      those during normal liver development. In conclusion, this study suggests that
      cancer cells with ABCG2 expression might play a central role in
      hepatocarcinogenesis and the maintenance of the cancer cell hierarchy of human
      HCC.

PMID- 17456780
TI  - Overexpression of carcinoma and embryonic cytotrophoblast cell-specific Mig-7
      induces invasion and vessel-like structure formation.
AB  - Molecular requirements for carcinoma cell interactions with the microenvironment
      are critical for disease progression but are poorly understood. Integrin alpha v
      beta 5, which senses the extracellular matrix, is important for carcinoma cell
      dissemination in vivo. alpha v beta 5 signaling induces Mig-7, a novel human gene
      product that is apparently carcinoma-specific. We hypothesized that Mig-7
      expression facilitates tumor cell dissemination by increasing invasion and
      vasculogenic mimicry. Results show that embryonic cytotrophoblasts up-regulated
      Mig-7 expression before they acquired an invasive phenotype capable of
      pseudovasculogenesis. Mig-7 protein primarily co-localized with vasculogenic
      mimicry markers factor VIII-associated antigen, vascular endothelial-cadherin,
      and laminin 5 gamma 2 chain domain III fragment in lymph node metastases.
      Overexpression of Mig-7 increased gamma 2 chain domain III fragments known to
      contain epidermal growth factor (EGF)-like repeats that can activate EGF
      receptor. Interestingly, EGF also induced Mig-7 expression. Carcinoma cell
      adhesion to laminins was significantly reduced by Mig-7 expression. Remarkably,
      in two-dimensional and three-dimensional Matrigel cultures, Mig-7 expression
      caused invasion and vessel-like structures. Melanoma cells, which were previously
      characterized to invade aggressively and to undergo vasculogenic mimicry,
      expressed Mig-7. Taken together, these data suggest that Mig-7 expression allows
      cells to sense their environment, to invade, and to form vessel-like structures
      through a novel relationship with laminin 5 gamma 2 chain domain III fragments.

PMID- 17456781
TI  - The host inflammatory response promotes liver metastasis by increasing tumor cell
      arrest and extravasation.
AB  - Inflammation can play a regulatory role in cancer progression and metastasis.
      Previously, we have shown that metastatic tumor cells entering the liver trigger
      a proinflammatory response involving Kupffer cell-mediated release of tumor
      necrosis factor-alpha and the up-regulation of vascular endothelial cell adhesion
      receptors, such as E-selectin. Here, we analyzed spatio-temporal aspects of the
      ensuing tumor-endothelial cell interaction using human colorectal carcinoma CX-1
      and murine carcinoma H-59 cells and a combination of immunohistochemistry,
      confocal microscopy, and three-dimensional reconstruction. E-selectin expression
      was evident mainly on sinusoidal vessels by 6 and 10 hours, respectively,
      following H-59 and CX-1 inoculation, and this corresponded to a stabilization of
      the number of tumor cells within the sinuses. Tumor cells arrested in E
      selectin(+) vessels and appeared to flatten and traverse the vessel lining, away
      from sites of intense E-selectin staining. This process was evident by 8 (H-59)
      and 12 (CX-1) hours after inoculation, coincided with increased endothelial
      vascular cell adhesion molecule-1 expression, and involved tumor cell attachment
      in areas of intense vascular cell adhesion molecule-1 and platelet endothelial
      cell adhesion molecule-1 expression. Nonmetastatic (human) MIP-101 and (murine) M
      27 cells induced a weaker response and could not be seen to extravasate. The
      results show that metastatic tumor cells can alter the hepatic microvasculature
      and use newly expressed endothelial cell receptors to arrest and extravasate.

PMID- 17456782
TI  - Oncogenic regulators and substrates of the anaphase promoting complex/cyclosome
      are frequently overexpressed in malignant tumors.
AB  - The fidelity of cell division is dependent on the accumulation and ordered
      destruction of critical protein regulators. By triggering the appropriately
      timed, ubiquitin-dependent proteolysis of the mitotic regulatory proteins
      securin, cyclin B, aurora A kinase, and polo-like kinase 1, the anaphase
      promoting complex/cyclosome (APC/C) ubiquitin ligase plays an essential role in
      maintaining genomic stability. Misexpression of these APC/C substrates,
      individually, has been implicated in genomic instability and cancer. However, no
      comprehensive survey of the extent of their misregulation in tumors has been
      performed. Here, we analyzed more than 1600 benign and malignant tumors by
      immunohistochemical staining of tissue microarrays and found frequent
      overexpression of securin, polo-like kinase 1, aurora A, and Skp2 in malignant
      tumors. Positive and negative APC/C regulators, Cdh1 and Emi1, respectively, were
      also more strongly expressed in malignant versus benign tumors. Clustering and
      statistical analysis supports the finding that malignant tumors generally show
      broad misregulation of mitotic APC/C substrates not seen in benign tumors,
      suggesting that a "mitotic profile" in tumors may result from misregulation of
      the APC/C destruction pathway. This profile of misregulated mitotic APC/C
      substrates and regulators in malignant tumors suggests that analysis of this
      pathway may be diagnostically useful and represent a potentially important
      therapeutic target.

PMID- 17456783
TI  - Phosphatidylethanolamine N-methyltransferase (PEMT) gene expression is induced by
      estrogen in human and mouse primary hepatocytes.
AB  - Choline is an essential nutrient for humans, though some of the requirement can
      be met by endogenous synthesis catalyzed by phosphatidylethanolamine N
      methyltransferase (PEMT). Premenopausal women are relatively resistant to choline
      deficiency compared with postmenopausal women and men. Studies in animals suggest
      that estrogen treatment can increase PEMT activity. In this study we investigated
      whether the PEMT gene is regulated by estrogen. PEMT transcription was increased
      in a dose-dependent manner when primary mouse and human hepatocytes were treated
      with 17-beta-estradiol for 24 h. This increased message was associated with an
      increase in protein expression and enzyme activity. In addition, we report a
      region that contains a perfect estrogen response element (ERE) approximately 7.5
      kb from the transcription start site corresponding to transcript variants
      NM_007169 and NM-008819 of the human and murine PEMT genes, respectively, three
      imperfect EREs in evolutionarily conserved regions and multiple imperfect EREs in
      nonconserved regions in the putative promoter regions. We predict that both the
      mouse and human PEMT genes have three unique transcription start sites, which are
      indicative of either multiple promoters and/or alternative splicing. This study
      is the first to explore the underlying mechanism of why dietary requirements for
      choline vary with estrogen status in humans.

PMID- 17456784
TI  - Apoptotic cells induce arginase II in macrophages, thereby attenuating NO
      production.
AB  - In recent years it has become apparent that removal of apoptotic cells (AC) by
      professional phagocytes alters the macrophage phenotype. This change is
      characterized by attenuated proinflammatory cytokine expression and NO
      production, which mechanistically remained unexplained. With the intention to
      explore molecular mechanisms underlying reduced NO formation, we showed that NO
      production in IFNgamma-stimulated murine RAW264.7 macrophages exposed to AC but
      not to either necrotic or viable human Jurkat cells was significantly reduced
      although iNOS expression remained high compared with controls. Analyzing iNOS
      activity in the cell extracts by using the radioactive L-arginine/citrulline
      conversion assay revealed increased ornithine production over citrulline in cells
      exposed to AC. RT-PCR, Western blot, and luciferase reporter analysis supported
      the idea of an arginase II increase in response to AC. The involvement of
      arginase in modulating NO formation in response to AC was substantiated by the
      arginase inhibitor N(omega)-hydroxy-nor-L-arginine. Moreover, knockdown of
      arginase II by siRNA allowed recovery of NO production. Experiments with AC
      conditioned medium demonstrated that a soluble lipid factor, rather than
      phagocytosis of AC, modulated NO production in macrophages. We conclude that AC
      release a lipid factor to modulate NO formation in macrophages via arginase II up
      regulation, thereby contributing to innate immune regulation.

PMID- 17456785
TI  - Transcriptional regulation of brain-derived neurotrophic factor in the amygdala
      during consolidation of fear memory.
AB  - We have demonstrated previously that brain-derived neurotrophic factor (BDNF)
      signaling in the amygdala is required for the consolidation of fear memory. This
      study is designed to characterize the signal cascades by which fear conditioning
      modulates transcriptional and translational expression of BDNF. Real-time reverse
      transcription-coupled polymerase chain reaction showed a significant increase in
      BDNF exon I- and III-containing mRNA in the amygdala of fear-conditioned rats,
      indicating that fear conditioning was capable of up-regulating BDNF mRNA.
      Bilateral administration of actinomycin D or anisomycin to the amygdala
      attenuated conditioning-induced increase in BDNF protein. Inhibitors for N-methyl
      d-aspartate (NMDA) receptor, L-type voltage-dependent calcium channel (L-VDCC),
      adenylyl cyclase, cAMP-dependent protein kinase (PKA), and calcium/calmodulin
      dependent kinase IV (CaMKIV) significantly reduced the increase. Moreover, DNA
      affinity precipitation and chromatin immunoprecipitation assays showed that
      phosphorylated cAMP response element-binding protein (p-CREB) binding activity in
      the proximal region of BDNF promoter I and III was significantly increased after
      fear conditioning. Intra-amygdala administration of cAMP response element decoy
      DNA before training impaired fear learning. Taken together, these results suggest
      that calcium influx through NMDA receptors and L-VDCCs during fear conditioning
      activates PKA and CaMKIV resulting in CREB phosphorylation. The phosphorylated
      CREB binds to BDNF promoter and up-regulates the expression of BDNF in the
      amygdala, which helps the consolidation of fear memory.

PMID- 17456786
TI  - Identification and characterization of a new tubulin-binding tetrasubstituted
      brominated pyrrole.
AB  - We studied the mechanism of action of 3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H
      pyrrole-2-carboxylic acid ethyl ester (JG-03-14) and found that it is a potent
      microtubule depolymerizer. JG-03-14 caused a dose-dependent loss of cellular
      microtubules, formation of aberrant mitotic spindles, accumulation of cells in
      the G(2)/M phase of the cell cycle, and Bcl-2 phosphorylation. These events
      culminated in the initiation of apoptosis, as evidenced by the caspase 3
      dependent cleavage of poly(ADP-ribose) polymerase (PARP). JG-03-14 has
      antiproliferative activity against a wide range of cancer cell lines, with an
      average IC(50) value of 62 nM, and it is a poor substrate for transport by P
      glycoprotein. JG-03-14 inhibited the polymerization of purified tubulin in vitro,
      consistent with a direct interaction between the compound and tubulin. JG-03-14
      potently inhibited the binding of [(3)H]colchicine to tubulin, suggesting that it
      bound to tubulin at a site overlapping the colchicine site. JG-03-14 had
      antitumor effects in the PC3 xenograft model, in which it caused greater than 50%
      reduction in tumor burden after 14 days of treatment. Molecular modeling studies
      indicated that the dimethoxyphenyl group of JG-03-14 occupies a space similar to
      that of the trimethoxyphenyl group of colchicine. However, the 2,3,5
      trisubstituted pyrrole group, which is connected to the dimethoxyphenyl moiety,
      interacted with both alpha and beta tubulin in space not shared with colchicine,
      suggesting significant differences compared with colchicine in the mechanism of
      binding to tubulin. Our results suggest that this tetransubstituted pyrrole
      represents a new, biologically active chemotype for the colchicine site on
      tubulin.

PMID- 17456787
TI  - Erlotinib, an effective epidermal growth factor receptor tyrosine kinase
      inhibitor, induces p27KIP1 up-regulation and nuclear translocation in association
      with cell growth inhibition and G1/S phase arrest in human non-small-cell lung
      cancer cell lines.
AB  - Erlotinib, a small-molecule epidermal growth factor receptor (EGFR) tyrosine
      kinase inhibitor, has been shown to have potent antitumor effects against human
      non-small-cell lung cancer (NSCLC) cell growth; however, the mechanism of such an
      effect is not elucidated. Here, we demonstrate that erlotinib-induced cell growth
      inhibition in EGFR high-expressing human H322 NSCLC cells was accompanied by G1/S
      phase arrest, which was largely caused by a decrease in expression of G1/S
      related cyclins, suppression of activities of cyclin-dependent kinase (CDK) 2 and
      CDK4, induction of CDK inhibitor p27(KIP1), and retinoblastoma
      hypophosphorylation. To further understand the role of p27(KIP1) in G1/S arrest
      and cell growth inhibition by erlotinib, we determined its effect on the
      expression of p27(KIP1) at transcriptional and posttranscriptional levels.
      Studies using real-time reverse transcription-polymerase chain reaction analysis
      and p27 promoter-driven luciferase reporter showed that erlotinib treatment
      resulted in the promotion of p27 gene transcription. In addition, erlotinib
      treatment led to an increase in p27(KIP1) half-life by inhibiting p27(KIP1)
      phosphorylation at Thr187 and by down-regulating Skp2 expression. Furthermore,
      immunofluorescence staining and cell fractionation showed that erlotinib
      treatment led to p27(KIP1) translocation to the nucleus. Knockdown of p27(KIP1)
      expression with p27(KIP1) small interfering RNA significantly abrogated erlotinib
      induced G1 phase arrest and cell growth inhibition, suggesting that induction of
      p27(KIP1) is required for G1 arrest and cell growth inhibition by erlotinib. It
      is noteworthy that we found that G1 arrest and p27(KIP1) up-regulation by
      erlotinib occurred in the tested sensitive cell lines but to a lesser extent in
      the resistant cell lines. Taken together, these results suggest that erlotinib
      inhibits human NSCLC cell growth predominantly by inducing p27(KIP1) expression
      and by suppressing cell-cycle events involved in the G1/S transition.

PMID- 17456788
TI  - Dynorphin knockout reduces fat mass and increases weight loss during fasting in
      mice.
AB  - Endogenous opioids, particularly dynorphins, have been implicated in regulation
      of energy balance, but it is not known how they mediate this in vivo. We
      investigated energy homeostasis in dynorphin knockout mice (Dyn(-/-) mice) and
      probed the interactions between dynorphins and the neuropeptide Y (NPY) system.
      Dyn(-/-) mice were no different from wild types with regards to body weight and
      basal and fasting-induced food intake, but fecal output was increased, suggesting
      decreased nutrient absorption, and they had significantly less white fat and lost
      more weight during a 24-h fast. The neuroendocrine and thermal responses to
      fasting were at least as pronounced in Dyn(-/-) as in wild types, and there was
      no stimulatory effect of dynorphin knockout on 24-h energy expenditure
      (kilocalories of heat produced) or physical activity. However, Dyn(-/-) mice
      showed increased circulating concentrations of 3,4-dihydroxyphenlacetic acid and
      3,4-dihydroxyphenylglycol, suggesting increased activity of the sympathetic
      nervous system. The respiratory exchange ratio of male but not female Dyn(-/-)
      mice was reduced, demonstrating increased fat oxidation. Interestingly,
      expression of the orexigenic acting NPY in the hypothalamic arcuate nucleus was
      reduced in Dyn(-/-) mice. However, fasting-induced increases in pre-prodynorphin
      expression in the arcuate nucleus, the paraventricular nucleus, and the
      ventromedial hypothalamus but not the lateral hypothalamus were abolished by
      deletion of Y(1) but not Y(2) receptors. Therefore, ablation of dynorphins
      results in increases in fatty acid oxidation in male mice, reductions in
      adiposity, and increased weight loss during fasting, possibly via increases in
      sympathetic activity, decreases in intestinal nutrient absorption, and
      interactions with the NPYergic system.

PMID- 17456789
TI  - Nuclear corepressor is required for inhibition of phosphoenolpyruvate
      carboxykinase expression by tumor necrosis factor-alpha.
AB  - Inhibition of phosphoenolpyruvate carboxykinase (PEPCK) by TNF-alpha contributes
      to the pathogenesis of hypoglycemia in endotoxin shock. In this study, the
      molecular mechanism underlying the inhibition was investigated in hepatoma cells
      (rat H4IIE and human HepG2). PEPCK expression was induced by cAMP, and the
      induction was reduced by TNF-alpha at protein and mRNA levels in H4IIE cells. The
      inhibition was observed in the PEPCK gene promoter in a PEPCK-luciferase
      reporter. Activation of nuclear factor kappaB (NF-kappaB) pathway was required
      for the transcriptional inhibition of PEPCK gene. Degradation of NF-kappaB
      inhibitor (IkappaB) and p65 nuclear translocation were involved in the
      inhibition. An interaction of histone deacetylase 3 (HDAC3) and silencing
      mediator for retinoic acid receptor and thyroid hormone receptor (SMRT) with the
      PEPCK gene promoter was induced by TNF-alpha and observed in a chromatin
      immunoprecipitation assay. The TNF-induced inhibition was blocked by HDAC
      inhibitor or HDAC3 knockdown. The blocking effect was also observed in knockdown
      of corepressor SMRT. Point mutation suggests that cAMP response element (CRE) is
      required for TNF-induced inhibition of the PEPCK gene promoter. Phosphorylation
      of cAMP response element-binding protein at Ser133 and expression of peroxisome
      proliferator-activated receptor-gamma coactivator 1alpha were not changed by TNF
      alpha in H4IIE cells. The transcriptional activity of CRE-binding protein was
      inhibited by TNF-alpha in a CRE-luciferase reporter. The data suggests that the
      nuclear corepressor proteins of HDAC3 and SMRT mediate TNF inhibition of PEPCK
      transcription. The inhibition mechanism is related to activation of NF-kappaB and
      inhibition of CRE-binding protein activity by the corepressor. These data suggest
      a novel activity of nuclear corepressor in the regulation of PEPCK expression by
      TNF-alpha.

PMID- 17456790
TI  - N-linked oligosaccharides direct the differential assembly and secretion of
      inhibin alpha- and betaA-subunit dimers.
AB  - The biosynthetic pathway governing inhibin heterodimer (alpha/beta) and activin
      homodimer (beta/beta) assembly and secretion from ovarian granulosa cells is not
      fully understood. Here, we examined the role of inhibin subunit glycosylation in
      the assembly and secretion of mature inhibin A and activin A. Inhibition of
      subunit glycosylation by tunicamycin treatment of alpha- and beta(A)-expressing
      CHO cell lines reduced inhibin but not activin secretion. Dimeric inhibin A is
      preferentially secreted from parental isogenic wild-type (wt) cell lines
      (alpha(wt)beta(wt)). Mutation of a single glycosylation site at asparagine 268
      (alpha(Delta268)beta(wt)) reduces inhibin secretion by 78% and permits beta/beta
      assembly and secretion. Conversely, gain of a glycosylation (GOG) site in the
      analogous region of the beta(A)-subunit (alpha(wt)beta(GOG327)) enhances inhibin
      A secretion. The present study demonstrates that N-linked glycan sites direct
      heterodimer vs. homodimer assembly, and prevention of glycosylation abrogates
      inhibin secretion. These data support a definitive role for site-specific N
      glycosylation in governing inhibin/activin dimer assembly and secretion.

PMID- 17456791
TI  - A mutation in Tpst2 encoding tyrosylprotein sulfotransferase causes dwarfism
      associated with hypothyroidism.
AB  - The growth-retarded (grt) mouse has an autosomal recessive, fetal-onset, severe
      thyroid hypoplasia related to TSH hyporesponsiveness. Through genetic mapping and
      complementation experiments, we show that grt is a missense mutation of a highly
      conserved region of the tyrosylprotein sulfotransferase 2 (Tpst2) gene, encoding
      one of the two Tpst genes implicated in posttranslational tyrosine O-sulfation.
      We present evidence that the grt mutation leads to a loss of TPST2 activity, and
      TPST2 isoform has a high degree of substrate preference for TSH receptor (TSHR).
      The expression of TPST2 can restore TSH-TSHR-mediated cAMP production in
      fibroblasts derived from grt mice. Therefore, we propose that the tyrosine
      sulfation of TSHR by TPST2 is crucial for TSH signaling and resultant thyroid
      gland function.

PMID- 17456792
TI  - Cellular expression levels of the vitamin D receptor are critical to its
      transcriptional regulation by the pituitary transcription factor Pit-1.
AB  - The biological role of 1,25-dihydroxyvitamin D(3) has generally been related to
      calcium homeostasis, but this hormone also has fundamental effects on processes
      of cellular proliferation and differentiation. The genomic actions of 1,25
      dihydroxyvitamin D(3) are mediated by the vitamin D receptor (VDR) present in
      target cells. However, VDR transcriptional regulation is not well understood,
      probably attributable to the complexity of the VDR gene and its promoter. In the
      present study, it is demonstrated that administration of the pituitary
      transcription factor Pit-1 (originally found in the pituitary gland but also
      present in other nonpituitary cell types and tissues) to the MCF-7 (human breast
      adenocarcinoma) cell line induces a significant increase in VDR mRNA and protein
      levels. Conversely, Pit-1-targeted small interference RNA markedly reduced
      expression of VDR in MCF-7 cells. Reporter gene assays demonstrated that the
      effect of Pit-1 is mediated by its binding to a region located between -254 and 
      246 bp from the VDR transcription start site. Selective mutations of this site
      completely abolished VDR transcription. Chromatin immunoprecipitation analysis
      showed that binding of Pit-1 to the VDR promoter leads additionally to
      recruitment of cAMP response element-binding protein binding protein, acetylated
      histone H4, and RNA polymerase II. Surprisingly, Pit-1 binding also recruits VDR
      protein to the VDR promoter. Using several cell lines with different levels of
      VDR expression, it was demonstrated that up-regulation of VDR transcription by
      Pit-1 is dependent on the presence of VDR protein, suggesting that
      transcriptional expression of VDR in a given cell type is dependent on, among
      other factors, its own expression levels.

PMID- 17456793
TI  - Estrogen-enhanced peptidylarginine deiminase type IV gene (PADI4) expression in
      MCF-7 cells is mediated by estrogen receptor-alpha-promoted transfactors
      activator protein-1, nuclear factor-Y, and Sp1.
AB  - Human peptidylarginine deiminase type IV (PAD4), a Ca(2+)-dependent enzyme known
      to convert arginine residues to citrulline residues in histones, has been shown
      to be associated with the development of rheumatoid arthritis. Recently, it was
      noted that the human peptidylarginine deiminase type IV gene (PADI4) regulates
      the expression of estrogen-responsive genes by modifying the methylated arginine
      sites in histones H3 and H4. In this study, we demonstrated that PADI4 was
      expressed in MCF-7 cells and was responsive to estrogen at the transcriptional
      level. Using the luciferase reporter gene fused to wild-type or mutated 5'
      flanking region of PADI4, we characterized that as few as 348 bp upstream from
      the transcription initiation site were sufficient to direct transcription of the
      reporter gene. Chromatin immunoprecipitation and small interfering RNA assays
      revealed that activator protein-1, Sp1/Sp3, and nuclear factor-Y were cis-acting
      factors bound to the minimal promoter of PADI4 and that they regulated gene
      expression in a cooperative manner. Moreover, it was indicated that estrogen
      stimulated PADI4 expression through binding of estrogen receptor (ER)-alpha to
      the upstream of the PADI4 gene and ERalpha-mediated enhancement of activator
      protein-1, Sp1, and nuclear factor-Y levels. These findings indicated that
      estrogen stimulated PADI4 expression through both of the classical and
      nonclassical ER-mediated pathways.

PMID- 17456794
TI  - Role of the growth hormone (GH) receptor transmembrane domain in receptor
      predimerization and GH-induced activation.
AB  - The GH receptor (GHR) mediates GH effects by activating the GHR-associated
      cytoplasmic tyrosine kinase, Janus kinase 2. Recent studies indicate that GHRs
      exist as dimers independently of GH binding. Some authors suggest that receptor
      predimerization is mediated by the transmembrane domain (TMD) and that GH binding
      initiates signaling by triggering changes in the orientation of the two GHRs
      within the dimer. In this study, we investigate the role of GHR TMD in GH
      independent receptor dimerization and ligand-induced activation. We prepared a
      GHR mutant, GHR(LDLR), in which the TMD is replaced with the TMD of the human low
      density lipoprotein receptor (LDLR). The resultant chimera has a TMD two residues
      shorter than the native GHR TMD; thus, in addition to possessing a different TMD,
      the altered GHR(LDLR) TMD helical register may change positions of the GHR
      extracellular domain (ECD) and intracellular domain relative to the TMD when
      compared with the wild-type (WT) receptor. When each was coexpressed with an
      intracellular domain-truncated GHR mutant, GHR(1-274-Myc), both WT GHR and
      GHR(LDLR) were specifically coprecipitated with GHR(1-274-Myc), indicating that
      the GHR TMD was not required for GHR heterodimerization with GHR(1-274-Myc). We
      further examined the contribution of the so-called "dimerization interface," a
      GHR ECD region that is critical for GH-induced signaling, to receptor
      predimerization. Coimmunoprecipitation experiments with either WT GHR, a
      dimerization interface mutant (GHR-H150D), or a control mutant (GHR-T147D) with
      GHR(1-274-Myc) showed dramatically reduced coprecipitation of GHR-H150D with
      GHR(1-274-Myc) when compared with WT GHR or GHR-T147K. This result suggests that,
      in contrast to some recent models, the dimerization interface contributes to GHR
      predimerization. We also compared WT GHR with GHR(LDLR) and GHR(LDLRDelta4) (a
      chimera in which the LDLR TMD has an internal deletion of four residues) with
      regard to response to GH stimulation. Although the chimeras had similar GH dose
      responses and time courses for signaling as WT GHR, they were markedly less
      sensitive to inhibition of signaling by a conformation-sensitive GHR ECD
      monoclonal antibody. Further, the chimeras were much less sensitive to inducible
      metalloprotease cleavage than was WT GHR, implying that the ECD conformations of
      the chimera receptors differ from WT GHR. Collectively, our data indicate that
      the composition and/or length of the TMD affect some aspects of GHR function, but
      do not affect receptor predimerization or GH-induced GHR activation. Further,
      they suggest that the GHR ECD-TMD is more flexible than previously thought in
      terms of the ability to achieve the active conformation in response to GH.

PMID- 17456795
TI  - Differential regulation of the human adrenocorticotropin receptor [melanocortin-2
      receptor (MC2R)] by human MC2R accessory protein isoforms alpha and beta in
      isogenic human embryonic kidney 293 cells.
AB  - The ACTH receptor [melanocortin-2 receptor (MC2R)] is the smallest known G
      protein-coupled receptor (GPCR). Herein, human MC2R accessory protein (MRAP)
      isoforms alpha and beta, cloned from a human fetal adrenal gland, were expressed
      with c-Myc-tagged MC2R (Myc-MC2R) in 293/Flp recombinase target site cells by
      homologous recombination. Although insertion of Myc-MC2R at the plasma membrane
      occurred without MRAP assistance, ACTH stimulation of cAMP production was only
      detected in cells coexpressing MC2R with either MRAP isoform. On the other hand,
      a MC2R-green fluorescent protein fusion transfected with either MRAPalpha or
      MRAPbeta was impaired both in cell membrane localization and signaling. MRAP
      isoforms were also tagged with either Flag or 6xHis epitopes. In cell populations
      coexpressing transiently and/or stably Myc-MC2R with MRAPalpha or MRAPbeta,
      stimulation with ACTH induced production of cAMP with EC(50) values lower in
      MRAPalpha- than in MRAPbeta-expressing cells. ACTH only bound Myc-MC2R in the
      presence of MRAP. Higher Myc-MC2R cell surface density was observed in the
      presence of MRAPbeta comparatively to MRAPalpha, possibly contributing to higher
      ACTH binding capacity and higher maximal cAMP responses observed in MRAPbeta
      expressing cells. Immunofluorescence studies indicated that MRAP isoforms were
      localized near the plasma membrane and in the vicinity, but not colocalized, with
      Myc-MC2R. In summary, through the generation of a new all-human experimental
      model devoid of endogenous MCRs, we present evidence that human MRAP isoforms,
      although not essential for MC2R localization at the plasma membrane, are
      essential for ACTH binding and ACTH-induced cAMP production and that they
      differentially regulate, although modestly, cell membrane density and functional
      properties of MC2R.

PMID- 17456796
TI  - The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand
      for the farnesoid and pregnane X receptors.
AB  - Cafestol, a diterpene present in unfiltered coffee brews such as Scandinavian
      boiled, Turkish, and cafetiere coffee, is the most potent cholesterol-elevating
      compound known in the human diet. Several genes involved in cholesterol
      homeostasis have previously been shown to be targets of cafestol, including
      cholesterol 7alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid
      biosynthesis. We have examined the mechanism by which cafestol elevates serum
      lipid levels. Changes in several lipid parameters were observed in cafestol
      treated APOE3Leiden mice, including a significant increase in serum triglyceride
      levels. Microarray analysis of these mice identified alterations in hepatic
      expression of genes involved in lipid metabolism and detoxification, many of
      which are regulated by the nuclear hormone receptors farnesoid X receptor (FXR)
      and pregnane X receptor (PXR). Further studies demonstrate that cafestol is an
      agonist ligand for FXR and PXR, and that cafestol down-regulates expression of
      the bile acid homeostatic genes CYP7A1, sterol 12alpha-hydroxylase, and Na(+)
      taurocholate cotransporting polypeptide in the liver of wild-type but not FXR
      null mice. Cafestol did not affect genes known to be up-regulated by FXR in the
      liver of wild-type mice, but did increase expression of the positive FXR-target
      genes intestinal bile acid-binding protein and fibroblast growth factor 15
      (FGF15) in the intestine. Because FGF15 has recently been shown to function in an
      enterohepatic regulatory pathway to repress liver expression of bile acid
      homeostatic genes, its direct induction in the gut may account for indirect
      effects of cafestol on liver gene expression. PXR-dependent gene regulation of
      cytochrome P450 3A11 and other targets by cafestol was also only seen in the
      intestine. Using a double FXR/PXR knockout mouse model, we found that both
      receptors contribute to the cafestol-dependent induction of intestinal FGF15 gene
      expression. In conclusion, cafestol acts as an agonist ligand for both FXR and
      PXR, and this may contribute to its impact on cholesterol homeostasis.

PMID- 17456797
TI  - Integration of steroid and growth factor pathways in breast cancer: focus on
      signal transducers and activators of transcription and their potential role in
      resistance.
AB  - The signaling pathways that are critical to the development and growth of breast
      cancer include those activated downstream of the estrogen receptor (ER) and the
      human epidermal growth factor receptor family. Many of these pathways, including
      the signal transducer and activator of transcription pathway, are common to both.
      The well-described genomic actions of ER involve its role as a transcription
      factor, either by binding directly to DNA through estrogen response elements, or
      by tethering to DNA through interaction with other proteins. Nongenomic signaling
      by the ER involves interaction with membrane-associated signaling proteins such
      as the c-Src tyrosine kinase and adapter proteins p130Cas and moderator of
      nongenomic activity of ER. Interactions with the signal transducer and activator
      of transcription pathway are important in both ER signaling pathways and are
      critical for estrogen-induced proliferation and tumorigenesis. These mechanisms
      of signaling cross talk and their role in resistance to antiestrogen therapies
      are discussed.

PMID- 17456799
TI  - Sirtuin functions in health and disease.
AB  - Sirtuins or Sir2 (silent information regulator 2)-related enzymes have originally
      been defined as a family of nicotinamide adenine dinucleotide-dependent enzymes
      that deacetylate lysine residue on various proteins. Certain sirtuins have in
      addition an ADP-ribosyltransferase activity. The sirtuins are remarkably
      conserved throughout evolution from archaebacteria to eukaryotes. The mammalian
      sirtuins SIRT1-SIRT7 are implicated in a variety of cellular functions ranging
      from gene silencing, over the control of the cell cycle and apoptosis, to energy
      homeostasis. On a whole-body level, the wide range of cellular activities of the
      sirtuins suggests that they could constitute therapeutic targets to combat
      metabolic, neurodegenerative, and proliferative diseases. Here, we review some of
      the recent data related to the sirtuins and discuss their mode of action, their
      biological role in cellular and organismal models, and their possible association
      to age-related human diseases.

PMID- 17456798
TI  - Receptor interacting protein 140 regulates expression of uncoupling protein 1 in
      adipocytes through specific peroxisome proliferator activated receptor isoforms
      and estrogen-related receptor alpha.
AB  - Expression of uncoupling protein 1 (Ucp1) mRNA is elevated in differentiated
      adipocytes derived from brown or white adipose tissue devoid of the nuclear
      receptor corepressor receptor interacting protein 140 (RIP140). Increased
      expression is mediated in part by the recruitment of peroxisome proliferator
      activated receptors alpha and gamma, together with estrogen-related receptor
      alpha, which functions through a novel binding site on the Ucp1 enhancer. This
      demonstrates that regulation of Ucp1 expression in the absence of RIP140 involves
      derepression of at least three different nuclear receptors. The ability to
      increase expression of Ucp1 by beta-adrenergic signaling is independent of
      RIP140, as shown by the action of the beta(3)-adrenergic agonist CL 316,243 to
      stimulate expression in both brown and white adipocytes in the presence and
      absence of the corepressor. Therefore, the expression of this metabolic
      uncoupling protein in adipose cells is regulated by inhibition as well as
      activation of distinct signaling pathways.

PMID- 17456800
TI  - Kinetics of mobilization and differentiation of lymphohematopoietic cells during
      experimental murine schistosomiasis in galectin-3 -/- mice.
AB  - Galectin-3 (gal-3), a beta-galactoside-binding animal lectin, plays a role in
      cell-cell and cell-extracellular matrix interactions. Extracellular gal-3
      modulates cell migration and adhesion in several physiological and pathological
      processes. Gal-3 is highly expressed in activated macrophages. Schistosoma
      mansoni eggs display a large amount of gal-3 ligands on their surface and elicit
      a well-characterized, macrophage-dependent, granulomatous, inflammatory reaction.
      Here, we have investigated the acute and chronic phases of S. mansoni infection
      in wild-type and gal-3(-/-) mice. In the absence of gal-3, chronic-phase
      granulomas were smaller in diameter, displaying thinner collagen fibers with a
      loose orientation. Schistosoma-infected gal-3(-/-) mice had remarkable changes in
      the monocyte/macrophage, eosinophil, and B lymphocyte subpopulations as compared
      with the infected wild-type mice. We observed a reduction of macrophage number,
      an increase in eosinophil absolute number, and a decrease in B lymphocyte
      subpopulation (B220(+/high) cells) in the periphery during the evolution of the
      disease in gal-3(-/-) mice. B lymphopenia was followed by an increase of plasma
      cell number in bone marrow, spleen, and mesenteric lymph nodes of the infected
      gal-3(-/-) mice. The plasma IgG and IgE levels also increased in these mice. Gal
      3 plays a role in the organization, collagen distribution, and mobilization of
      inflammatory cells to chronic-phase granulomas, niches for extramedullary
      myelopoiesis, besides interfering with monocyte-to-macrophage and B cell-to
      plasma cell differentiation.

PMID- 17456801
TI  - Large defects of type I allergic response in telomerase reverse transcriptase
      knockout mice.
AB  - Telomerase is critically important for the maintenance of a constant telomere
      length, which in turn, is related to the concepts of longevity and oncogenesis.
      In addition, it has been well documented that telomerase activity is expressed in
      immune cells in a highly regulated manner. We have studied systemic anaphylaxis
      in mouse telomerase reverse transcriptase knockout (mTERT(-/-)) mice to
      understand the significance of telomerase activity and telomere stability in mast
      cells, which induce a type I allergic response. Compared with wild-type mice,
      mTERT(-/-) mice displayed largely attenuated, IgE-mediated, passive anaphylactic
      responses, which were observed even in the early generations of mTERT(-/-) mice,
      and had decreased numbers of mast cells in vivo and impaired development of bone
      marrow-derived mast cells (BMMCs) induced by IL-3 or stem cell factor in vitro.
      Moreover, in mTERT(-/-) mice, BMMCs exhibited a large morphology and low
      proliferation rate, while they possessed a comparable degranulation capacity and
      cell surface expression level of c-kit and FcepsilonRI. These findings imply that
      telomerase activity has a definitive impact on the type I allergic response by
      altering the character of effecter mast cells.

PMID- 17456802
TI  - Maturation of the mucosal immune system underlies colitis susceptibility in
      interleukin-10-deficient (IL-10-/-) mice.
AB  - Elevated mucosal IL-12/23p40 and IFN-gamma accompany early inflammation in IL-10
      deficient (IL-10(-/-)) mice and then later decline while inflammation persists.
      This report addresses whether this cytokine profile reflects disease progression
      or inherent, age-related changes in mucosal immunity. IL-10(-/-) and wild-type
      (WT) mice were maintained in an ultrabarrier facility or transferred to
      conventional housing at 3, 12, or 30 weeks of age. Weight, stool changes, and
      histologic features were followed. Lamina propria mononuclear cells were cultured
      for cytokine analysis by ELISA. Ultrabarrier-housed IL-10(-/-) mice are
      statistically indistinguishable from WT mice by weight, disease activity index,
      and histologic inflammation. IL-10(-/-) mice but not WT, transferred at 3 weeks,
      develop colitis gradually, reaching a significant, sustained maximum by 15 weeks
      of age. Transfer at 12 weeks induces rapid disease onset in both strains, maximal
      at 15 weeks of age. Inflammation persists in IL-10(-/-), and WT recover. IL-10(-/
      ) and WT mice transferred at 30 weeks demonstrate transient diarrhea and weight
      loss but no chronic inflammation. Probiotics delay symptom onset only in the 12
      week-old group. IFN-gamma production from ultrabarrier-housed IL-10(-/-) mice is
      elevated at 12 weeks of age, and older animals have decreased IFN-gamma and
      increased IL-4. IL-10 is important for suppressing inflammation after transfer at
      3 weeks of age and limiting inflammation after transfer at 12 weeks but has
      little influence at 30 weeks of age. Colitis onset, progression, and response to
      probiotic therapy vary with immune system age, suggesting that a distinct, Th1
      driven, age-dependent cytokine profile may contribute to increased colitis
      susceptibility in otherwise healthy mice.

PMID- 17456803
TI  - G-protein-coupled receptor expression, function, and signaling in macrophages.
AB  - G-protein-coupled receptors (GPCRs) are widely targeted in drug discovery. As
      macrophages are key cellular mediators of acute and chronic inflammation, we
      review here the role of GPCRs in regulating macrophage function, with a focus on
      contribution to disease pathology and potential therapeutic applications. Within
      this analysis, we highlight novel GPCRs with a macrophage-restricted expression
      profile, which provide avenues for further exploration. We also review an
      emerging literature, which documents novel roles for GPCR signaling components in
      GPCR-independent signaling in macrophages. In particular, we examine the
      crosstalk between GPCR and TLR signaling pathways and highlight GPCR signaling
      molecules which are likely to have uncharacterized functions in this cell
      lineage.

PMID- 17456804
TI  - Focus issue: from egg to egg--cell signaling in germ cells.
AB  - In this Focus Issue of Science's STKE, which complements the Science Special
      Issue on germ cells, we take a closer look at cell signaling in germ cells. STKE
      highlights the migration of germ cells with an article that describes the
      different mechanisms controlling primordial germ cell movement and survival in
      mice and flies. Another article describes a mechanism for mediating plant self
      incompatibility through control of the pollen tube, to prevent inappropriate
      delivery of incompatible sperm to the ovule. A common feature found in each of
      the organisms discussed, be they animal, insect or plant, is that signals from
      the surrounding tissues control survival and migration of the germ cells or
      resulting gametes.

PMID- 17456805
TI  - What is left behind--quality control in germ cell migration.
AB  - Cell differentiation, cell proliferation, cell death, and cell migration are
      tightly controlled during animal development and adult homeostasis. Failure to
      regulate these processes can result in tumor formation and metastasis. Aberrant
      cells are therefore often cleared by induction of cell death. Recent work has
      elucidated the mechanism of elimination of mouse primordial germ cells that fail
      to migrate properly and highlights the similarity of this mechanism to those
      governing the same phenomenon in Drosophila. In addition, these studies
      underscore the different functions a single signaling pathway can have in
      controlling cell survival, cell proliferation, and cell migration during
      different phases of development.

PMID- 17456806
TI  - Pollen-pistil signaling in self-incompatible poppy: does it allow more efficient
      resource allocation in the pistil?
AB  - In the process of pollination, haploid pollen germinates on the stigma surface
      and a pollen tube grows through the diploid tissues of the pistil toward the
      ovary. The pistil has two basic functions: to prevent unwanted pollen from
      gaining access to the ovary and to support the growth of desirable pollen. Pollen
      pistil signaling allows these different types of pollen to be distinguished. Self
      incompatibility (SI) systems, controlled by the S locus, are the best-understood
      pollen-pistil signaling systems. Other SI systems have been investigated at the
      molecular level, but the physiology of pollen tube rejection is best understood
      in the field poppy, Papaver rhoeas. This species has a gametophytic SI system:
      Pollen is rejected when its S haplotype is the same as either of the two S
      haplotypes expressed in the diploid pistil. Recent advances reveal new ways that
      SI controls pollen tube metabolism. A soluble pyrophosphatase is down-regulated
      as part of the rapid SI response, and, over the long term, perturbations of the
      actin cytoskeleton lead to programmed cell death in incompatible pollen tubes.
      Manipulating incompatible pollen tube metabolism in this way may leave more
      resources available for supporting the growth of compatible pollen tubes, the
      complementary function of the pistil.

PMID- 17456807
TI  - The cover. Young Christian Girl.

PMID- 17456808
TI  - A piece of my mind. At a loss for words.

PMID- 17456809
TI  - Epidurals' benefit for back pain questioned.

PMID- 17456810
TI  - JCAHO tweaks emergency departments' pneumonia treatment standards.

PMID- 17456811
TI  - Anesthesia-Alzheimer disease link probed.

PMID- 17456812
TI  - Centers to weave addiction treatment into medical education.

PMID- 17456813
TI  - Clopidogrel and long-term outcomes after drug-eluting stent implantation.

PMID- 17456814
TI  - Clopidogrel and long-term outcomes after drug-eluting stent implantation.

PMID- 17456815
TI  - Clopidogrel and long-term outcomes after drug-eluting stent implantation.

PMID- 17456816
TI  - Clopidogrel and long-term outcomes after drug-eluting stent implantation.

PMID- 17456817
TI  - Pharmacy care programs and clinical outcomes.

PMID- 17456818
TI  - Effect of 10 days of bed rest on skeletal muscle in healthy older adults.

PMID- 17456819
TI  - Effects of ranolazine on recurrent cardiovascular events in patients with non-ST
      elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial.
AB  - CONTEXT: Ranolazine is a novel antianginal agent that reduces ischemia in
      patients with chronic angina but has not been studied in patients with acute
      coronary syndromes (ACS). OBJECTIVE: To determine the efficacy and safety of
      ranolazine during long-term treatment of patients with non-ST-elevation ACS.
      DESIGN, SETTING, AND PATIENTS: A randomized, double-blind, placebo-controlled,
      multinational clinical trial of 6560 patients within 48 hours of ischemic
      symptoms who were treated with ranolazine (initiated intravenously and followed
      by oral ranolazine extended-release 1000 mg twice daily, n = 3279) or matching
      placebo (n = 3281), and followed up for a median of 348 days in the Metabolic
      Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary
      Syndromes (MERLIN)-TIMI 36 trial between October 8, 2004, and February 14, 2007.
      MAIN OUTCOME MEASURES: The primary efficacy end point was a composite of
      cardiovascular death, myocardial infarction (MI), or recurrent ischemia through
      the end of study. The major safety end points were death from any cause and
      symptomatic documented arrhythmia. RESULTS: The primary end point occurred in 696
      patients (21.8%) in the ranolazine group and 753 patients (23.5%) in the placebo
      group (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.83-1.02; P =
      .11). The major secondary end point (cardiovascular death, MI, or severe
      recurrent ischemia) occurred in 602 patients (18.7%) in the ranolazine group and
      625 (19.2%) in the placebo group (HR, 0.96; 95% CI, 0.86-1.08; P = .50).
      Cardiovascular death or MI occurred in 338 patients (10.4%) allocated to
      ranolazine and 343 patients (10.5%) allocated to placebo (HR, 0.99; 95% CI, 0.85
      1.15; P = .87). Recurrent ischemia was reduced in the ranolazine group (430
      [13.9%]) compared with the placebo group (494 [16.1%]; HR, 0.87; 95% CI, 0.76
      0.99; P = .03). QTc prolongation requiring a reduction in the dose of intravenous
      drug occurred in 31 patients (0.9%) receiving ranolazine compared with 10
      patients (0.3%) receiving placebo. Symptomatic documented arrhythmias did not
      differ between the ranolazine (99 [3.0%]) and placebo (102 [3.1%]) groups (P =
      .84). No difference in total mortality was observed with ranolazine compared with
      placebo (172 vs 175; HR, 0.99; 95% CI, 0.80-1.22; P = .91). CONCLUSIONS: The
      addition of ranolazine to standard treatment for ACS was not effective in
      reducing major cardiovascular events. Ranolazine did not adversely affect the
      risk of all-cause death or symptomatic documented arrhythmia. Our findings
      provide support for the safety and efficacy of ranolazine as antianginal therapy.
      TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00099788.

PMID- 17456820
TI  - Invasive pneumococcal disease caused by nonvaccine serotypes among alaska native
      children with high levels of 7-valent pneumococcal conjugate vaccine coverage.
AB  - CONTEXT: With routine childhood vaccination using heptavalent pneumococcal
      conjugate vaccine, one concern has been the potential for emergence and expansion
      of replacement disease caused by serotypes not contained in the heptavalent
      conjugate vaccine. OBJECTIVE: To determine whether replacement disease is
      associated with the overall decline in invasive pneumococcal disease among Alaska
      Native children. DESIGN, SETTING, AND PATIENTS: Alaska statewide longitudinal
      population-based laboratory surveillance of invasive Streptococcus pneumoniae
      infections from January 1, 1995, through December 31, 2006. MAIN OUTCOME
      MEASURES: Incidence and types of pneumococcal disease in children younger than 2
      years. RESULTS: In the first 3 years after introduction of routine vaccination
      with heptavalent pneumococcal conjugate vaccine, overall invasive pneumococcal
      disease decreased 67% in Alaska Native children younger than 2 years (from 403.2
      per 100,000 in 1995-2000 to 134.3 per 100,000 per year in 2001-2003, P<.001).
      However, between 2001-2003 and 2004-2006, there was an 82% increase in invasive
      disease in Alaska Native children younger than 2 years to 244.6/100,000 (P =
      .02). Since 2004, the invasive pneumococcal disease rate caused by nonvaccine
      serotypes has increased 140% compared with the prevaccine period (from 95.1 per
      100,000 in 1995-2000 to 228.6 in 2004-2006, P = .001). During the same period,
      there was a 96% decrease in heptavalent vaccine serotype disease. Serotype 19A
      accounted for 28.3% of invasive pneumococcal disease among Alaska children
      younger than 2 years during 2004-2006. There was no significant increase in
      nonvaccine disease in non-Native Alaska children younger than 2 years.
      CONCLUSIONS: Alaska Native children are experiencing replacement invasive
      pneumococcal disease with serotypes not covered by heptavalent pneumococcal
      conjugate vaccine. The demonstration of replacement invasive pneumococcal disease
      emphasizes the importance of ongoing surveillance and development of expanded
      valency vaccines.

PMID- 17456821
TI  - Association of CFH Y402H and LOC387715 A69S with progression of age-related
      macular degeneration.
AB  - CONTEXT: Studies have reported that single-nucleotide polymorphisms in the genes
      CFH and LOC387715 are associated with age-related macular degeneration (AMD).
      OBJECTIVE: To assess whether these genetic variants have prognostic importance
      for progression to advanced AMD and related visual loss. DESIGN, SETTING, AND
      PARTICIPANTS: Prospective analysis of 1466 white participants in the Age-Related
      Eye Disease Study (AREDS), a US multicenter clinical trial conducted from 1990 to
      2001 with a mean follow-up time of 6.3 years. Age-related macular degeneration
      status was determined by grading of fundus photographs. Progression (n = 281) was
      defined as newly diagnosed advanced AMD (geographic atrophy, exudative disease,
      or AMD causing visual loss) in one or both eyes during the course of the study.
      Genotypic analysis was conducted in 2006. MAIN OUTCOME MEASURE: Incidence rates
      of dry and neovascular advanced AMD. RESULTS: The CFH Y402H and LOC387115 A69S
      polymorphisms were each independently related to progression from early or
      intermediate stages to advanced stages of AMD, controlling for demographic
      factors, smoking, body mass index, and AREDS vitamin-mineral treatment
      assignment, with odds ratios (ORs) of 2.6 (95% confidence interval [CI], 1.7-3.9)
      for CFH and 4.1 (95% CI, 2.7-6.3) for LOC387715 for the homozygous risk genotypes
      (P<.001 for trend for each additional risk allele for both genes). The effect of
      LOC387715 was stronger for progression to neovascular disease (OR, 6.1; 95% CI,
      3.3-11.2) compared with geographic atrophy (OR, 3.0; 95% CI, 1.4-6.5) relative to
      no progression for the homozygous risk state. The presence of all adverse factors
      (both risk genotypes, smoking, and body mass index > or =25) increased risk 19
      fold. Smoking and high body mass index increased odds of progression within each
      risk genotype. Genetic plus nongenetic risk scores provided an area under the
      receiver operating characteristic curve of up to 0.78. CONCLUSIONS: Common
      polymorphisms in the genes CFH and LOC387715 are independently related to AMD
      progression after adjustment for other known AMD risk factors. Presence of these
      polymorphisms plus smoking [corrected] and body mass index of 25 or higher,
      controlling for AREDS vitamin-mineral treatment, identifies [corrected] patients
      who are highly susceptible to developing advanced states [corrected] of this
      visually disabling disease.

PMID- 17456822
TI  - Derivation and validation of a simplified predictive index for renal replacement
      therapy after cardiac surgery.
AB  - CONTEXT: A predictive index for renal replacement therapy (RRT; hemodialysis or
      continuous venovenous hemodiafiltration) after cardiac surgery may improve
      clinical decision making and research design. OBJECTIVES: To develop a predictive
      index for RRT using preoperative information. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective cohort of 20 131 cardiac surgery patients at 2 hospitals in
      Ontario, Canada. The derivation cohort consisted of 10,751 patients at Toronto
      General Hospital (1999-2004). The validation cohorts consisted of 2566 patients
      at Toronto General Hospital (2004-2005) and 6814 patients at Ottawa Heart
      Institute (1999-2003). MAIN OUTCOME MEASURE: Postoperative RRT. RESULTS: RRT
      rates in the derivation, Toronto validation, and Ottawa validation cohorts were
      1.3%, 1.8%, and 2.2%, respectively. Multivariable predictors of RRT were
      preoperative estimated glomerular filtration rate, diabetes mellitus requiring
      medication, left ventricular ejection fraction, previous cardiac surgery,
      procedure, urgency of surgery, and preoperative intra-aortic balloon pump. The
      predictive index was scored from 0 to 8 points. An estimated glomerular
      filtration rate less than or equal to 30 mL/min was assigned 2 points; other
      components were assigned 1 point each: estimated glomerular filtration rate 31 to
      60 mL/min, diabetes mellitus, ejection fraction less than or equal to 40%,
      previous cardiac surgery, procedure other than coronary artery bypass grafting,
      intra-aortic balloon pump, and nonelective case. Among the 53% of patients with
      low risk scores (< or =1), the risk of RRT was 0.4%; by comparison, this risk was
      10% among the 6% of patients with high-risk scores (> or =4). The predictive
      index had areas under the receiver operating characteristic curve in the
      derivation, Toronto validation, and Ottawa validation cohorts of 0.81, 0.78, and
      0.78, respectively. When these cohorts were stratified based on index scores,
      likelihood ratios for RRT were more concordant than observed RRT rates.
      CONCLUSIONS: RRT after cardiac surgery is predicted by readily available
      preoperative information. A simple predictive index based on this information
      discriminated well between low- and high-risk patients in derivation and
      validation cohorts. The index had improved generalizability when used to predict
      likelihood ratios for RRT.

PMID- 17456823
TI  - Does this patient with a pericardial effusion have cardiac tamponade?
AB  - CONTEXT: Cardiac tamponade is a state of hemodynamic compromise resulting from
      cardiac compression by fluid trapped in the pericardial space. The clinical
      examination may assist in the decision to perform pericardiocentesis in patients
      with cardiac tamponade diagnosed by echocardiography. OBJECTIVE: To
      systematically review the accuracy of the history, physical examination, and
      basic diagnostic tests for the diagnosis of cardiac tamponade. DATA SOURCES:
      MEDLINE search of English-language articles published between 1966 and 2006,
      reference lists of these articles, and reference lists of relevant textbooks.
      STUDY SELECTION: We included articles that compared aspects of the clinical
      examination to a reference standard for the diagnosis of cardiac tamponade. We
      excluded studies with fewer than 15 patients. Of 787 studies identified by our
      search strategy, 8 were included in our final analysis. DATA EXTRACTION: Two
      authors independently reviewed articles for study results and quality. A third
      reviewer resolved disagreements. DATA SYNTHESIS: All studies evaluated patients
      with known tamponade or those referred for pericardiocentesis with known
      effusion. Five features occur in the majority of patients with tamponade: dyspnea
      (sensitivity range, 87%-89%), tachycardia (pooled sensitivity, 77%; 95%
      confidence interval [CI], 69%-85%), pulsus paradoxus (pooled sensitivity, 82%;
      95% CI, 72%-92%), elevated jugular venous pressure (pooled sensitivity, 76%; 95%
      CI, 62%-90%), and cardiomegaly on chest radiograph (pooled sensitivity, 89%; 95%
      CI, 73%-100%). Based on 1 study, the presence of pulsus paradoxus greater than 10
      mm Hg in a patient with a pericardial effusion increases the likelihood of
      tamponade (likelihood ratio, 3.3; 95% CI, 1.8-6.3), while a pulsus paradoxus of
      10 mm Hg or less greatly lowers the likelihood (likelihood ratio, 0.03; 95% CI,
      0.01-0.24). CONCLUSIONS: Among patients with cardiac tamponade, a minority will
      not have dyspnea, tachycardia, elevated jugular venous pressure, or cardiomegaly
      on chest radiograph. A pulsus paradoxus greater than 10 mm Hg among patients with
      a pericardial effusion helps distinguish those with cardiac tamponade from those
      without. Diagnostic certainty of the presence of tamponade requires additional
      testing.

PMID- 17456824
TI  - The right brain hypothesis for obesity.

PMID- 17456825
TI  - Does ranolazine have a place in the treatment of acute coronary syndromes?

PMID- 17456826
TI  - Invasive pneumococcal disease: the target is moving.

PMID- 17456827
TI  - JAMA patient page. Pericardial effusion.

PMID- 17456828
TI  - Use of an electronic medical record for the identification of research subjects
      with diabetes mellitus.
AB  - Diabetes mellitus is a rapidly increasing and costly public health problem. Large
      studies are needed to understand the complex gene-environment interactions that
      lead to diabetes and its complications. The Marshfield Clinic Personalized
      Medicine Research Project (PMRP) represents one of the largest population-based
      DNA biobanks in the United States. As part of an effort to begin phenotyping
      common diseases within the PMRP, we now report on the construction of a diabetes
      case-finding algorithm using electronic medical record data from adult subjects
      aged > or =50 years living in one of the target PMRP ZIP codes. Based upon
      diabetic diagnostic codes alone, we observed a false positive case rate ranging
      from 3.0% (in subjects with the highest glycosylated hemoglobin values) to 44.4%
      (in subjects with the lowest glycosylated hemoglobin values). We therefore
      developed an improved case finding algorithm that utilizes diabetic diagnostic
      codes in combination with clinical laboratory data and medication history. This
      algorithm yielded an estimated prevalence of 24.2% for diabetes mellitus in adult
      subjects aged > or =50 years.

PMID- 17456829
TI  - Evaluation of genetic factors for warfarin dose prediction.
AB  - OBJECTIVES: Warfarin is a commonly prescribed anticoagulant drug used to prevent
      thromboses that may arise as a consequence of orthopedic and vascular surgery or
      underlying cardiovascular disease. Warfarin is associated with a notoriously
      narrow therapeutic window where small variations in dosing may result in
      hemorrhagic or thrombotic complications. To ultimately improve dosing of
      warfarin, we evaluated models for stable maintenance dose that incorporated both
      clinical and genetic factors. METHOD: A model was constructed by evaluating the
      contribution to dosing variability of the following clinical factors: age,
      gender, body surface area, and presence or absence of prosthetic heart valves or
      diabetes. The model was then sequentially expanded by incorporating polymorphisms
      of cytochrome P450 (CYP) 2C9; vitamin K 2,3 epoxide reductase complex, subunit 1
      (VKORC1); gamma carboxylase; factor VII; and apolipoprotein (Apo) E genes.
      RESULTS: Of genetic factors evaluated in the model, CYP2C9 and VKORC1 each
      contributed substantially to dose variability, and together with clinical factors
      explained 56% of the individual variability in stable warfarin dose. In contrast,
      gamma carboxylase, factor VII and Apo E polymorphisms contributed little to dose
      variability. CONCLUSION: The importance of CYP2C9 and VKORC1 to patient-specific
      dose of warfarin has been confirmed, while polymorphisms of gamma carboxylase,
      factor VII and Apo E genes did not substantially contribute to predictive models
      for stable warfarin dose.

PMID- 17456830
TI  - Scabies--a hypersensitive subject.

PMID- 17456831
TI  - Diagnosis--hydatid cyst disease.

PMID- 17456832
TI  - An evidence-based update on nonsteroidal anti-inflammatory drugs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs), including both traditional
      nonselective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are
      widely used for their anti-inflammatory and analgesic effects. NSAIDs are a
      necessary choice in pain management because of the integrated role of the COX
      pathway in the generation of inflammation and in the biochemical recognition of
      pain. This group of drugs has recently come under scrutiny because of recent
      focus in the literature on the various adverse effects that can occur when
      applying NSAIDs. This review will provide an educational update on the current
      evidence of the efficacy and adverse effects of NSAIDs. It aims to answer the
      following questions: (1) are there clinically important differences in the
      efficacy and safety between the different NSAIDs, (2) if there are differences,
      which are the ones that are more effective and associated with fewer adverse
      effects, and (3) which are the effective therapeutic approaches that could reduce
      the adverse effects of NSAIDs. Finally, an algorithm is proposed which delineates
      a general decision-making tree to select the most appropriate analgesic for an
      individual patient based on the evidence reviewed.

PMID- 17456834
TI  - Better management of cardiovascular diseases by pulse wave velocity: combining
      clinical practice with clinical research using evidence-based medicine.
AB  - Arterial stiffness measured by pulse wave velocity (PWV) is an accepted strong,
      independent predictor of cardiovascular events and mortality. However, lack of a
      reliable reference range has limited its use in clinical practice. In this
      evidence-based review, we applied published data to develop a PWV risk
      stratification model and demonstrated its impact on the management of common
      clinical scenarios. After reviewing 97 studies where PWV was measured, 5 end
      stage renal disease patients, 5 hypertensives, 2 diabetics, and 2 elderly studies
      were selected. Pooling the data by the "fixed-effect model" demonstrated that the
      mortality and cardiovascular event risk ratio for one level increment in PWV was
      2.41 (1.81-3.20) or 1.69 (1.35-2.11), respectively. There was a significant
      difference in PWV between survived and deceased groups, both in the low and high
      risk populations. Furthermore, risk comparison demonstrated that 1 standard
      deviation increment in PWV is equivalent to 10 years of aging, or 1.5 to 2 times
      the risk of a 10 mmHg increase in systolic blood pressure. Evidence shows that
      PWV can be beneficially used in clinical practice for cardiovascular risk
      stratification. Furthermore, the above risk estimates could be incorporated into
      currently used cardiac risk scores to improve their predictive power and
      facilitate the clinical application of PWV.

PMID- 17456833
TI  - Lessons from BRCA: the tubal fimbria emerges as an origin for pelvic serous
      cancer.
AB  - Ovarian epithelial cancer is diagnosed in approximately 25,000 women yearly in
      the United States, accounting for approximately 12,500 deaths. Of these tumors,
      serous cancer is the most lethal, due to its capacity to spread beyond the
      reproductive tract and involve the peritoneal surfaces or distant organs.
      Conventional classification systems designate tumor origins principally on the
      location of the largest tumor. However, despite the fact that the largest tumors
      typically involve the ovaries, demonstrations of a precise starting point for
      these tumors, including precursor lesions, have been inconsistent. In recent
      years, a major effort to prevent serous cancer in genetically susceptible women
      with mutations in BRCA1 or BRCA2 has spawned the practice of prophylactic
      salpingo-oophorectomy. This practice has surprisingly revealed that many early
      cancers in these women arise in the fallopian tube, and further studies have
      pinpointed the distal (fimbrial) portion as the most common site of origin.
      Emerging studies that carefully examine the fallopian tubes suggest a high
      frequency of early cancer in the fimbria in unselected women with ovarian and
      peritoneal serous carcinoma, raising the distinct possibility that a significant
      proportion of these tumors have a fimbrial origin. The evidence for these
      discoveries and their relevance to serous cancer classification, early detection
      and prevention are addressed in this review. A model for pelvic serous cancer is
      proposed that takes into account five distinct variables which ultimately impact
      on origin and tumor distribution: (1) location of target epithelium, (2)
      genotoxic stress, (3) type of epithelium, (4) mitigating genetic factors, and (5)
      tumor spread pattern. Ultimately, this model illustrates the importance of
      identifying cancer precursors, inasmuch as these entities are useful as both
      surrogate endpoints for their respective malignancies in epidemiologic studies
      and natural targets for cancer prevention.

PMID- 17456835
TI  - Plastic biliary stent occlusion: factors involved and possible preventive
      approaches.
AB  - Endoscopic biliary stenting is today the most common palliative treatment for
      patients suffering from obstructive jaundice associated with malignant
      hepatobiliary tumors or benign strictures. However, recurrent jaundice, with or
      without cholangitis, is a major complication of a biliary endoprosthesis
      insertion. Thus, stent removal and replacement with a new one frequently occurs
      as a consequence of device blockage caused by microbial biofilm growth and
      biliary sludge accumulation in the lumen. Factors and mechanisms involved in
      plastic stent clogging arising from epidemiological, clinical and experimental
      data, as well as the possible strategies to prevent biliary stent failure, will
      be reviewed and discussed.

PMID- 17456836
TI  - Utility of the clinical dementia rating in Asian populations.
AB  - Consistent with the worldwide demographic trend of population aging, dementia is
      expected to become a burgeoning public health problem in Asian populations. Thus,
      there is a pressing need for reliable and valid methods of dementia diagnosis and
      staging that are applicable in heterogeneous Asian populations. The Clinical
      Dementia Rating (CDR) is an informant-based global assessment scale with
      established reliability and validity that has been widely utilized as a severity
      ranking scale in many studies of Asian populations. From a diagnostic standpoint,
      the CDR is congruent with the Diagnostic and Statistical Manual of Mental
      Disorders approach of dementia diagnosis. It exhibits excellent discriminatory
      ability in the very mild stages of dementia, a useful property that is germane to
      the surging interest in mild cognitive impairment and related concepts.
      Limitations of the CDR include its length of administration, reliance on clinical
      judgment and collateral source information, and relative insensitivity as a
      measure of change in interventional studies. Since the exercise of clinical
      judgment is inherent in scoring, CDR raters should be mindful of the influence of
      cultural factors on premorbid lifestyle, informant reliability and performance in
      certain CDR test items (especially those pertaining to the categories of judgment
      and problem solving, community, and home and hobbies). Thus, in future studies
      that involve the nascent use of the CDR in Asian populations, it is recommended
      that any transcultural adaptation of CDR items be described in detail and
      appropriate validation studies be carried out before adopting the CDR as a
      yardstick measure of assessment. The potential of adapted versions of the CDR in
      chronic care settings and advanced cases should be explored. An integrative
      approach, combining brief informant interview in conjunction with brief objective
      cognitive testing, could be a viable strategy for dementia screening in the
      clinical and research setting that warrants further evaluation in Asian
      populations.

PMID- 17456838
TI  - Bone size normalizes with age in children and adolescents with type 1 diabetes.
AB  - OBJECTIVE: The aim of this study was to establish whether type 1 diabetes has a
      long-term effect on bone development in children and adolescents. RESEARCH DESIGN
      AND METHODS: Bone characteristics and muscle cross-sectional area (CSA) were
      analyzed cross-sectionally in 41 (19 female and 22 male) patients and were
      reevaluated after 5.56 +/- 0.4 years using peripheral quantitative computed
      tomography (pQCT). We hypothesize that bone size and muscle mass normalize with
      age. RESULTS: At the first evaluation, mean +/- SD age was 9.87 +/- 2.3 years and
      disease duration was 4.31 +/- 2.9 years. Height was -0.36 +/- 1.9 SD, and BMI was
      0.39 +/- 0.9 SD. Parameters of bone size were low in the whole patient group
      (corrected for patient's height). At reevaluation, age was 15.44 +/- 2.3 years,
      and patients had a mean height of -0.12 +/- 0.8 SD. BMI SD had increased to 0.57
      +/- 1.1. Total and cortical CSA had normalized. Those patients with an increase
      in total CSA had a significant younger age at disease manifestation and a younger
      age at initial pQCT measurement. Bone size was well adapted to muscle mass
      expressed as the ratio of bone mineral content per muscle mass, and a close
      correlation was shown between the increase in bone size and in muscle CSA (r =
      0.46, P = 0.03). CONCLUSIONS: Patients with manifestation of type 1 diabetes at
      an early age had transient impaired bone development. Within the follow-up
      period, the greatest increase in bone size was found in these patients. In
      adolescence, all patients had a normal bone size and appropriate adaptation of
      bone on muscle.

PMID- 17456837
TI  - Unequal efficacy of pyridinium oximes in acute organophosphate poisoning.
AB  - The use of organophosphorus pesticides results in toxicity risk to non-target
      organisms. Organophosphorus compounds share a common mode of action, exerting
      their toxic effects primarily via acetylcholinesterase (AChE) inhibition.
      Consequently, acetylcholine accumulates in the synaptic clefts of muscles and
      nerves, leading to overstimulation of cholinergic receptors. Acute cholinergic
      crisis immediately follows exposure to organophosphate and includes signs and
      symptoms resulting from hyperstimulation of central and peripheral muscarinic and
      nicotinic receptors. The current view of the treatment of organophosphate
      poisoning includes three strategies, i.e. the use of an anticholinergic drug
      (e.g., atropine), cholinesterase-reactivating agents (e.g., oximes) and
      anticonvulsant drugs (e.g., benzodiazepines). Oximes, as a part of antidotal
      therapy, ensure the recovery of phosphylated enzymes via a process denoted as
      reactivation of inhibited AChE. However, both experimental results and clinical
      findings have demonstrated that different oximes are not equally effective
      against poisonings caused by structurally different organophosphorus compounds.
      Therefore, antidotal characteristics of conventionally used oximes can be
      evaluated regarding how close the certain substance is to the theoretical concept
      of the universal oxime. Pralidoxime (PAM-2), trimedoxime (TMB-4), obidoxime (LuH
      6), HI-6 and HLo-7 have all been demonstrated to be very effective in
      experimental poisonings with sarin and VX. TMB-4 and LuH-6 may reactivate tabun
      inhibited AChE, whereas HI-6 possesses the ability to reactivate the soman
      inhibited enzyme. An oxime HLo-7 seems to be an efficient reactivator of AChE
      inhibited by any of the four organophosphorus warfare agents. According to the
      available literature, the oximes LuH-6 and TMB-4, although relatively toxic, are
      the most potent to induce reactivation of AChE inhibited by the majority of
      organophosphorus pesticides. Since there are no reports of controlled clinical
      trials on the use of TMB-4 in human organophosphate pesticide poisoning, LuH-6
      may be a better option.

PMID- 17456839
TI  - AIR inhaled insulin in subjects with chronic obstructive pulmonary disease:
      pharmacokinetics, glucodynamics, safety, and tolerability.
AB  - OBJECTIVE: In this open-label, randomized, crossover study, pharmacokinetic and
      glucodynamic responses were compared in healthy subjects versus subjects with
      moderate chronic obstructive pulmonary disease (COPD), following administration
      of 12 units equivalent AIR inhaled insulin versus 12 units subcutaneous insulin
      lispro. RESEARCH DESIGN AND METHODS: Three nonsmoking groups (n = 15 each)-
      healthy subjects (baseline mean +/- SD age 38 +/- 13 years, forced expiratory
      volume in 1 s [FEV1] 4.06 +/- 1.04 l), subjects with chronic bronchitis (aged 53
      +/- 9 years, FEV1 2.14 +/- 0.60 l), and subjects with pulmonary emphysema (aged
      58 +/- 6 years, FEV1 1.67 +/- 0.61 l)--were randomly assigned to one of three
      treatment sequences. Three euglycemic glucose clamp procedures were performed.
      RESULTS: In subjects with chronic bronchitis and emphysema, AIR inhaled insulin
      administration resulted in reduced insulin exposure (area under the serum insulin
      concentration curve from time zero until time of return to baseline [AUC(0-t')])
      (55.7%, P = 0.13 and 78.5%, P < 0.001, respectively) and reduced total insulin
      effect (total glucose infusion rate) (60.4%, P < 0.01 and 67.1%, P < 0.01,
      respectively) relative to healthy subjects. Subcutaneous insulin lispro
      administration resulted in similar responses across study groups for insulin
      exposure and metabolic effect. Intrasubject pharmacokinetic and glucodynamic
      variability ranged from 17 to 52% across groups. No significant differences were
      shown for pre- and postclamp pulmonary function tests. During clamps, FEV1 and
      forced vital capacity declined modestly in both COPD groups, with no difference
      between AIR insulin and subcutaneous insulin lispro. CONCLUSIONS: Short-term
      exposure to AIR inhaled insulin was well tolerated by COPD subjects, showing
      similar time-exposure and time-action profiles, but with reduced insulin
      absorption and metabolic effect compared with healthy subjects. Further clinical
      evaluation is warranted in patients with comorbid diabetes and COPD.

PMID- 17456840
TI  - Elevated cystatin C concentration and progression to pre-diabetes: the Western
      New York study.
AB  - OBJECTIVE: We conducted a nested case-control investigation to examine whether
      elevated baseline concentrations of cystatin C predicted progression from
      normoglycemia to pre-diabetes over 6 years of follow-up from the Western New York
      Health Study. RESEARCH DESIGN AND METHODS: In 2002-2004, 1,455 participants from
      the Western New York Health Study, who were free of type 2 diabetes and known
      cardiovascular disease at baseline (1996-2001), were reexamined. An incident case
      of pre-diabetes was defined as an individual with fasting glucose < 100 mg/dl at
      the baseline examination and > or = 100 and < or = 125 mg/dl at the follow-up
      examination, thereby eliminating individuals with prevalent pre-diabetics. All
      case patients (n = 91) were matched 1:3 to control participants based on sex,
      race/ethnicity, and year of study enrollment. All control subjects had fasting
      glucose levels < 100 mg/dl at both baseline and follow-up examinations. Cystatin
      C concentrations and the urinary albumin-to-creatinine ratio were measured from
      frozen (-196 degrees C) baseline blood and urine samples. Serum creatinine
      concentrations were available from the baseline examination only. RESULTS:
      Multivariate conditional logistic regression analyses adjusted for age, baseline
      glucose level, homeostasis model assessment of insulin resistance, BMI,
      hypertension, estimated glomerular filtration rate, cigarette smoking, and
      alcohol use revealed a significantly increased risk of progression to pre
      diabetes among those with elevated baseline concentrations of cystatin C (odds
      ratio 3.28 [95% CI 1.43-7.54]) (upper quintile versus the remainder). Results of
      secondary analyses that considered high-sensitivity C-reactive protein,
      interleukin-6, E-selectin, or soluble intercellular adhesion molecule-1 did not
      alter these results. CONCLUSIONS: These results suggest that cystatin C was
      associated with a threefold excess risk of progression to pre-diabetes in this
      population.

PMID- 17456841
TI  - Central obesity is an independent risk factor for albuminuria in nondiabetic
      South Asian subjects.
AB  - OBJECTIVE: South Asians have a high prevalence of central obesity. When the
      diagnosis of diabetes is made, they have a very high risk of developing renal
      failure. In the current study, we explored the hypothesis that central obesity is
      associated with the development of renal injury, before the manifestation of
      diabetes. RESEARCH DESIGN AND METHODS: We invited first-degree nondiabetic
      relatives of South Asian type 2 diabetic patients for investigation of
      microalbuminuria and diabetes. Subjects who used antihypertensive or antidiabetic
      medication were excluded. We performed a glucose tolerance test according to the
      classic World Health Organization criteria. A total of 205 subjects were
      normoglycemic; we excluded 25 subjects because of impaired glucose tolerance, and
      30 subjects were excluded because of de novo diabetes. Central obesity was
      measured by waist-to-hip ratio (WHR). Albuminuria was measured as albumin-to
      creatinine ratio (ACR) in the early-morning urine. RESULTS: Central obesity was
      independently related with albuminuria in the 205 normoglycemic subjects. We
      found no relation of fasting blood glucose or systolic blood pressure with
      albuminuria. Multivariate analysis for the presence of increased albuminuria
      (median ACR >0.31 mg/mmol) showed a relative risk of 4.1 for the highest versus
      the lowest tertile of WHR (P = 0.002). CONCLUSIONS: Central obesity is an early
      and independent risk factor for increased albuminuria in normoglycemic South
      Asian subjects. This could explain the high incidence of diabetic renal disease
      in South Asians, probably by the mechanism of insulin resistance and endothelial
      dysfunction in the pre-diabetic state.

PMID- 17456842
TI  - Asymmetric dimethylarginine predicts cardiovascular events in patients with type
      2 diabetes.
AB  - OBJECTIVE: Circulating concentrations of an endogenous inhibitor of nitric oxide
      synthase, asymmetric dimethylarginine (ADMA), are elevated in patients with
      increased cardiovascular risk. We hypothesized that ADMA predicts cardiovascular
      events and enhances risk prediction independent of established risk markers in
      patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This prospective
      cohort study included 125 patients with type 2 diabetes. ADMA, L-arginine, high
      sensitivity C-reactive protein (CRP), and routine clinical parameters were
      determined at baseline. First occurrence of cardiovascular events (myocardial
      infarction, percutaneous coronary intervention, coronary artery bypass graft,
      stroke, carotid revascularization, or all-cause mortality) was defined as a
      composite end point. RESULTS: During a median follow-up of 21 (interquartile
      range 11-27) months, 84 events occurred in 48 patients. According to multivariate
      Cox regression analysis, patients with baseline ADMA or CRP in the highest
      tertile had a significantly increased hazard ratio for incident cardiovascular
      events compared with those with ADMA or CRP in tertile 1 (2.37 [95% CI 1.05
      5.35], P = 0.038, and 3.63 [1.59-8.28], P = 0.002). Assessing the joint effect of
      ADMA and CRP revealed that patients with either ADMA or CRP or both in the
      highest tertile had increased hazard ratios for cardiovascular events compared
      with patients with neither ADMA nor CRP in the highest tertile before and after
      adjustment for possible confounders (hazard ratio 4.59 [95% CI 2.07-10.15], P <
      0.001). CONCLUSIONS: ADMA predicted cardiovascular events and enhanced the
      predictive role of CRP in patients with type 2 diabetes. ADMA therefore could
      improve cardiovascular risk assessment in patients with type 2 diabetes.

PMID- 17456843
TI  - Clustering of multiple healthy lifestyle habits and health-related quality of
      life among U.S. adults with diabetes.
AB  - OBJECTIVE: We sought to examine the association between clustering of multiple
      healthy lifestyle habits (HLHs) and health-related quality of life (HRQOL) among
      adults with diabetes. RESEARCH DESIGN AND METHODS: We analyzed the representative
      sample of the civilian, noninstitutionalized U.S. population aged > or = 18 years
      with diabetes using data from the 2005 Behavioral Risk Factor Surveillance System
      (n = 16,428). Four HRQOL measures were general health rating, physically
      unhealthy days, mentally unhealthy days, and impaired activity days. Three HLHs
      included not smoking, engaging in adequate leisure time physical activity, and
      consuming five or more servings of fruits and vegetables per day. RESULTS: The
      proportion of having 0, 1, 2, and 3 HLHs was 10.5, 44.7, 32.9, and 11.9%,
      respectively. The age-adjusted prevalence rates of poor or fair health, > or = 14
      physically unhealthy days, > or = 14 mentally unhealthy days, and > or = 14
      impaired activity days were 43.07, 27.61, 17.22, and 18.87%, respectively. After
      adjustment for potential confounders and comparison with none of the three HLHs,
      people with all three HLHs were less likely to report poor or fair health
      (adjusted odds ratio 0.49 [95% CI 0.33-0.71]), > or = 14 physically unhealthy
      days (0.56 [0.39-0.80]), > or = 14 mentally unhealthy days (0.35 [0.23-0.55]), or
      > or = 14 impaired activity days (0.35 [0.23-0.56]). CONCLUSIONS: Accumulation of
      multiple HLHs was significantly associated with better HRQOL among people with
      diabetes.

PMID- 17456844
TI  - Telmisartan shows an equivalent effect of vitamin C in further improving
      endothelial dysfunction after glycemia normalization in type 1 diabetes.
AB  - OBJECTIVE: Long-lasting hyperglycemia in type 1 diabetic patients induces
      permanent alterations of endothelial function by increased oxidative stress, even
      when glycemia is normalized. RESEARCH DESIGN AND METHODS: In this study, 36 type
      1 diabetic patients and 12 control subjects were enrolled. The diabetic patients
      were divided into three groups. The first group was treated for 24 h with
      insulin, achieving a near normalization of glycemia. After 12 h of this
      treatment, vitamin C was added for the remaining 12 h. The second group was
      treated for 24 h with vitamin C. After 12 h of this treatment, insulin was
      started, achieving a near normalization of glycemia for the remaining 12 h. The
      third group was treated for 24 h with both vitamin C and insulin, achieving near
      normalization of glycemia. The same protocols were performed after 1 month of
      telmisartan or placebo. RESULTS: Neither normalization of glycemia nor vitamin C
      treatment alone was able to normalize endothelial dysfunction or oxidative
      stress. Combining insulin and vitamin C normalized endothelial dysfunction and
      decreased oxidative stress to normal levels. Telmisartan significantly improved
      basal endothelial function and decreased nitrotyrosine plasma levels. In patients
      treated with telmisartan, a near normalization of both flow-mediated vasodilation
      and oxidative stress was achieved when glycemia was normalized, whereas adding
      vitamin C infusion did not show further effect on endothelial function or
      nitrotyrosine plasma levels. CONCLUSIONS: These data indicate that combining the
      normalization of glycemia with an antioxidant can normalize endothelial function
      in type 1 diabetic patients and that telmisartan works as an antioxidant like
      vitamin C.

PMID- 17456845
TI  - Intra-abdominal fat and elevated urine albumin excretion in men with type 1
      diabetes.

PMID- 17456847
TI  - Impaired fat oxidation after a single high-fat meal in insulin-sensitive
      nondiabetic individuals with a family history of type 2 diabetes.
AB  - Individuals with insulin resistance and type 2 diabetes have an impaired ability
      to switch appropriately between carbohydrate and fatty acid oxidation. However,
      whether this is a cause or consequence of insulin resistance is unclear, and the
      mechanism(s) involved in this response is not completely elucidated. Whole-body
      fat oxidation and transcriptional regulation of genes involved in lipid
      metabolism in skeletal muscle were measured after a prolonged fast and after
      consumption of either high-fat (76%) or high-carbohydrate (76%) meals in
      individuals with no family history of type 2 diabetes (control, n = 8) and in age
      and fatness-matched individuals with a strong family history of type 2 diabetes
      (n = 9). Vastus lateralis muscle biopsies were performed before and 3 h after
      each meal. Insulin sensitivity and fasting measures of fat oxidation were not
      different between groups. However, subjects with a family history of type 2
      diabetes had an impaired ability to increase fatty acid oxidation in response to
      the high-fat meal (P < 0.05). This was related to impaired activation of genes
      involved in lipid metabolism, including those for peroxisome proliferator
      activated receptor coactivator-1alpha (PGC1alpha) and fatty acid translocase
      (FAT)/CD36 (P < 0.05). Of interest, adiponectin receptor-1 expression decreased
      23% after the high-fat meal in both groups, but it was not changed after the high
      carbohydrate meal. In conclusion, an impaired ability to increase fatty acid
      oxidation precedes the development of insulin resistance in genetically
      susceptible individuals. PGC1alpha and FAT/CD36 are likely candidates in
      mediating this response.

PMID- 17456846
TI  - Nkx2.2 regulates beta-cell function in the mature islet.
AB  - Nkx2.2 is a homeodomain transcription factor that is critical for pancreatic
      endocrine cell specification and differentiation in the developing mouse embryo.
      The purpose of this study was to determine whether Nkx2.2 is also required for
      the maintenance and function of the mature beta-cell in the postnatal islet. We
      have demonstrated previously that a repressor derivative of Nkx2.2 can
      functionally substitute for endogenous Nkx2.2 to fully restore alpha- and
      immature beta-cells in the embryonic islet; however, Nkx2.2 activator functions
      appear to be required to form a functional beta-cell. In this study, we have
      created transgenic mouse lines to express the Nkx2.2-repressor derivative in the
      mature beta-cell in the presence of endogenous Nkx2.2. The transgenic mice were
      assessed for beta-cell function, overall islet structure, and expression of beta
      cell-specific markers. Using this transgenic approach, we have determined that
      the Nkx2.2-repressor derivative disrupts endogenous Nkx2.2 expression in adult
      mice and causes downregulation of the mature beta-cell factors, MafA and Glut2.
      Consistently, the Nkx2.2-repressor mice display reduced insulin gene expression
      and pancreatic insulin content and impaired insulin secretion. At weaning, the
      male Nkx2.2-repressor mice are overtly diabetic and all Nkx2.2-repressor
      transgenic mice exhibit glucose intolerance. Furthermore, the loss of beta-cell
      function in the Nkx2.2-repressor transgenic mice is associated with disrupted
      islet architecture. These studies indicate a previously undiscovered role for
      Nkx2.2 in the maintenance of mature beta-cell function and the formation of
      normal islet structure.

PMID- 17456848
TI  - Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal
      antibody.
AB  - Anti-CD3 monoclonal antibody (mAb) has been shown to induce tolerance and to be
      an effective treatment for diabetes both in animal models and in human trials. We
      have shown that anti-CD3 mAb given orally is biologically active in the gut and
      suppresses experimental autoimmune encephalitis by the induction of a regulatory
      T-cell that expresses latency-associated peptide (LAP) on its surface. In the
      present study, we investigated the effect of oral anti-CD3 mAb on the prevention
      of autoimmune diabetes in AKR mice in which the low-dose streptozocin (STZ) model
      induces autoimmunity to the beta-cells of the islets. We found that oral anti-CD3
      mAb given at doses of 50 and 250 microg/feeding suppressed the incidence of
      diabetes in this model with the best effects seen at the 50 microg/dose.
      Associated with suppression, we observed decreased cell proliferation in the
      spleen and conversion of T-helper (Th)1 responses into Th2/Th3 responses in the
      periphery, including the pancreatic lymph nodes. Oral anti-CD3 mAb increased the
      expression of LAP on CD4(+) T-cells, and these cells could adoptively transfer
      protection. Protection by oral anti-CD3 was transforming growth factor-beta
      dependent. Our results demonstrate that oral anti-CD3 is effective in the model
      of STZ-induced diabetes and may be a useful form of therapy for type 1 diabetes
      in humans.

PMID- 17456849
TI  - Alzheimer-like changes in rat models of spontaneous diabetes.
AB  - OBJECTIVE: To examine whether changes characteristic of Alzheimer's disease occur
      in two rat models with spontaneous onset of type 1 and type 2 diabetes. RESEARCH
      DESIGN AND METHODS: The frontal cortices of 8-month-diabetic rats were examined
      with respect to neuronal densities, neurite degeneration, expression, and/or
      immunolocalization of amyloid precursor protein (APP), beta-secretase, beta
      amyloid, COOH-terminal fragment (CTF), insulin receptor, IGF-1 receptor, glycogen
      synthase kinase 3-beta (GSK-3beta), protein kinase B (Akt), phosphorylated tau
      (phospho-tau), synaptophysin, and phosphorylated neurofilaments (SMI-31).
      RESULTS: Neuronal loss occurred in both models, significantly more so in type 2
      diabetic BBZDR/Wor rats compared with type 1 diabetic BB/Wor rats and was
      associated with a ninefold increase of dystrophic neurites. APP, beta-secretase,
      beta-amyloid, and CTF were significantly increased in type 2 diabetic rats, as
      was phospho-tau. The insulin receptor expression was decreased in type 1
      diabetes, whereas IGF-1 receptor was decreased in both models, as were Akt and
      GSK-3beta expression. CONCLUSIONS: The data show that beta-amyloid and phospho
      tau accumulation occur in experimental diabetes and that this is associated with
      neurite degeneration and neuronal loss. The changes were more severe in the type
      2 diabetic model and appear to be associated with insulin resistance and possibly
      hypercholesterolemia. The two models will provide useful tools to unravel further
      mechanistic associations between diabetes and Alzheimer's disease.

PMID- 17456850
TI  - Metabolic endotoxemia initiates obesity and insulin resistance.
AB  - Diabetes and obesity are two metabolic diseases characterized by insulin
      resistance and a low-grade inflammation. Seeking an inflammatory factor causative
      of the onset of insulin resistance, obesity, and diabetes, we have identified
      bacterial lipopolysaccharide (LPS) as a triggering factor. We found that normal
      endotoxemia increased or decreased during the fed or fasted state, respectively,
      on a nutritional basis and that a 4-week high-fat diet chronically increased
      plasma LPS concentration two to three times, a threshold that we have defined as
      metabolic endotoxemia. Importantly, a high-fat diet increased the proportion of
      an LPS-containing microbiota in the gut. When metabolic endotoxemia was induced
      for 4 weeks in mice through continuous subcutaneous infusion of LPS, fasted
      glycemia and insulinemia and whole-body, liver, and adipose tissue weight gain
      were increased to a similar extent as in high-fat-fed mice. In addition, adipose
      tissue F4/80-positive cells and markers of inflammation, and liver triglyceride
      content, were increased. Furthermore, liver, but not whole-body, insulin
      resistance was detected in LPS-infused mice. CD14 mutant mice resisted most of
      the LPS and high-fat diet-induced features of metabolic diseases. This new
      finding demonstrates that metabolic endotoxemia dysregulates the inflammatory
      tone and triggers body weight gain and diabetes. We conclude that the LPS/CD14
      system sets the tone of insulin sensitivity and the onset of diabetes and
      obesity. Lowering plasma LPS concentration could be a potent strategy for the
      control of metabolic diseases.

PMID- 17456851
TI  - Long-term exposure to glucose and lipids inhibits glucose-induced insulin
      secretion downstream of granule fusion with plasma membrane.
AB  - Mouse beta-cells cultured at 15 mmol/l glucose for 72 h had reduced ATP-sensitive
      K+ (K(ATP)) channel activity (-30%), increased voltage-gated Ca2+ currents,
      higher intracellular free Ca2+ concentration ([Ca2+]i; +160%), more exocytosis
      (monitored by capacitance measurements, +100%), and greater insulin content
      (+230%) than those cultured at 4.5 mmol/l glucose. However, they released 20%
      less insulin when challenged with 20 mmol/l glucose. Glucose-induced (20 mmol/l)
      insulin secretion was reduced by 60-90% in islets cocultured at 4.5 or 15 mmol/l
      glucose and either oleate or palmitate (0.5 mmol/l). Free fatty acid (FFA)
      induced inhibition of secretion was not associated with any major changes in
      [Ca2+]i or islet ATP content. Palmitate stimulated exocytosis by twofold or more
      but reduced K+-induced secretion by up to 60%. Basal (1 mmol/l glucose) K(ATP)
      channel activity was 40% lower in islets cultured at 4.5 mmol/l glucose plus
      palmitate and 60% lower in islets cultured at 15 mmol/l glucose plus either of
      the FFAs. Insulin content decreased by 75% in islets exposed to FFAs in the
      presence of high (15 mmol/l), but not low (4.5 mmol/l), glucose concentrations,
      but the number of secretory granules was unchanged. FFA-induced inhibition of
      insulin secretion was not associated with increased transcript levels of the
      apoptosis markers Bax (BclII-associated X protein) and caspase-3. We conclude
      that glucose and FFAs reduce insulin secretion by interference with the exit of
      insulin via the fusion pore.

PMID- 17456852
TI  - Hematopoietic stem cells derived from adult donors are not a source of pancreatic
      beta-cells in adult nondiabetic humans.
AB  - OBJECTIVE: Type 1 and type 2 diabetes are characterized by an approximately 98
      and approximately 65% loss of pancreatic beta-cells, respectively. Efforts to
      reverse either form of diabetes increasingly focus on the possibility of
      promoting beta-cell replacement and/or regeneration. Islet transplantation has
      been explored, but it does not provide long-term insulin independence. One
      possible source of beta-cell regeneration is hematopoietic stem cells. In mice,
      there are conflicting data as to whether hematopoietic stem cells contribute to
      pancreatic beta-cells. We sought to establish whether hematopoietic stem cells
      (derived from adult donors) transdifferentiate into pancreatic beta-cells in
      adult humans. RESEARCH DESIGN AND METHODS: We addressed this in 31 human
      pancreata obtained at autopsy from hematopoietic stem cell transplant recipients
      who had received their transplant from a donor of the opposite sex. RESULTS:
      Whereas some donor-derived cells were observed in the nonendocrine pancreata, no
      pancreatic beta-cells were identified that were derived from donor hematopoietic
      stem cells, including two cases with type 2 diabetes. CONCLUSIONS: We conclude
      that hematopoietic stem cells derived from adult donors contribute minimally to
      pancreatic beta-cells in nondiabetic adult humans. These data do not rule out the
      possibility that hematopoietic stem cells contribute to pancreatic beta-cells in
      childhood or in individuals with type 1 diabetes.

PMID- 17456853
TI  - Renal fibrosis and glomerulosclerosis in a new mouse model of diabetic
      nephropathy and its regression by bone morphogenic protein-7 and advanced
      glycation end product inhibitors.
AB  - Diabetic nephropathy is currently the most common cause of end-stage renal
      disease (ESRD) in the western world. A mouse model for diabetic nephropathy that
      encompasses the salient features of this disease in the kidney is not available.
      Here, we report that CD1 mice, in contrast to inbred C57BL/6 and 129Sv strains,
      develop ESRD associated with prominent tubulointerstitial nephritis and fibrosis
      within 3 months and die because of diabetic complications by 6-7 months after a
      single injection of streptozotocin. Histopathologic lesions observed in these
      mice mimic human diabetic nephropathy, including glomerular hypertrophy, diffuse
      glomerulosclerosis, tubular atrophy, interstitial fibrosis, and decreased renal
      excretory function. Next, we tested the therapeutic efficacy of bone morphogenic
      protein-7 (BMP-7) and inhibitors of advanced glycation end products (AGEs),
      aminoguanidine and pyridoxamine, to inhibit and regress the progression of renal
      disease in diabetic CD1 mice. We demonstrate that although aminoguanidine,
      pyridoxamine, and BMP-7 significantly inhibit glomerular lesions, BMP-7 is most
      effective in the inhibition of tubular inflammation and tubulointerstitial
      fibrosis in these mice. Collectively, our results report a new mouse model for
      diabetic nephropathy with prominent interstitial inflammation and fibrosis and
      the selective inhibition of diabetic kidney disease by AGE inhibitors and BMP-7.

PMID- 17456854
TI  - Adipose mitochondrial biogenesis is suppressed in db/db and high-fat diet-fed
      mice and improved by rosiglitazone.
AB  - The objective of this study was to further establish and confirm the relationship
      of adipose mitochondrial biogenesis in diabetes/obesity and the effects of
      rosiglitazone (RSG), a peroxisome proliferator-activated receptor (PPAR) gamma
      agonist, by systematically analyzing mitochondrial gene expression and function
      in two mouse models of obesity and type 2 diabetes. Using microarray technology,
      adipose mitochondrial gene transcription was studied in db/db, high-fat diet-fed
      C57BL/6 (HFD) and respective control mice with or without RSG treatment. The
      findings were extended using mitochondrial staining, DNA quantification, and
      measurements of citrate synthase activity. In db/db and HFD mice, gene
      transcripts associated with mitochondrial ATP production, energy uncoupling,
      mitochondrial ribosomal proteins, outer and inner membrane translocases, and
      mitochondrial heat-shock proteins were decreased in abundance, compared with db/+
      and standard-fat diet-fed control mice, respectively. RSG dose-dependently
      increased these transcripts in both db/db and HFD mice and induced transcription
      of mitochondrial structural proteins and cellular antioxidant enzymes responsible
      for removal of reactive oxygen species generated by increased mitochondrial
      activity. Transcription factors, including PPAR coactivator (PGC)-1beta, PGC
      1alpha, estrogen-related receptor alpha, and PPARalpha, were suppressed in both
      models and induced by RSG. The effects of RSG on adipose mitochondrial genes were
      confirmed by quantitative RT-PCR and further supported by mitochondrial staining,
      mitochondrial DNA quantification, and citrate synthase activity. Adipose
      mitochondrial biogenesis was overwhelmingly suppressed in both mouse models of
      diabetes/obesity and globally induced by RSG. These findings suggest an important
      role of adipose mitochondria in diabetes/obesity and the potential for new
      treatment approaches targeting adipose mitochondria.

PMID- 17456855
TI  - Diffusion of clean indoor air ordinances in the southwestern United States.
AB  - The authors investigate the process through which clean indoor air ordinances
      were considered in 10 communities in the southwestern United States and key
      factors that influenced diffusion and adoption. Clean indoor air ordinances,
      which ban smoking in public places, were adopted in approximately 1,409 U.S.
      communities from 1986 to April 2004. The authors gathered data from 10
      communities in New Mexico and Texas by means of face-to-face interview, e-mail,
      and telephone interviews and by analyzing archival materials. Important
      influences on the adoption or rejection of clean indoor air ordinances were (a)
      personal experiences of policy champions, (b) local framing of the ordinance as a
      public health issue versus as an economic/ business or an individual rights
      issue, and (c) interpersonal networks connecting a community to previously
      adopting communities. The policies that were adopted ranged in comprehensiveness,
      with each community of study reinventing model policies obtained from other
      communities.

PMID- 17456856
TI  - Self-efficacy as a predictor to PFMT adherence in a prevention of urinary
      incontinence clinical trial.
AB  - Past research suggests a positive correlation between self-efficacy (SE) and
      adherence to behavioral interventions. Less is known about SE and adherence in
      behavioral programs that are preventive in nature and specific to urinary
      incontinence (UI). Using treatment-group data from a previously reported
      randomized controlled trial, the authors assess the role of SE in predicting
      adherence to pelvic-floor muscle training (PFMT) for UI prevention in a sample of
      postmenopausal women. Results indicate that at 12 months follow-up, nearly 70% of
      participants reported medium or high adherence, performing the recommended PFMT
      regimen 2 to 3 times per week or more. Summary scores of both Task SE, beta =
      .25, SE (beta) = .08, p < .01, and Regulatory SE, beta = .43, SE (beta) = .06, p
      < .0001, predict adherence. Also, the authors found a modest decline in self
      efficacy scores over time. These findings highlight the importance of SE in
      sustained behavioral change.

PMID- 17456857
TI  - Spousal support and food-related behavior change in middle-aged and older adults
      living with type 2 diabetes.
AB  - One of the most challenging diabetes-related behavior changes is adhering to a
      healthful diet. Drawing on the social cognitive theory and social support
      literature, this qualitative study explores how spousal support influences
      dietary changes following a diagnosis of type 2 diabetes in middle-aged and older
      adults. The purpose of this study was to determine how aspects of the spousal
      relationship translate into behavior changes, specifically adherence to a
      healthful diet. Analyses revealed five core themes related to dietary adherence:
      control over food, dietary competence, commitment to support, spousal
      communication, and coping with diabetes. The themes can be categorized within two
      key social cognitive theory constructs: reinforcement and self-efficacy.
      Implications from the focus group data can inform the development of more
      effective, targeted nutrition messages and programs to provide specific knowledge
      and skills.

PMID- 17456858
TI  - The relationship between the social environment within religious organizations
      and intake of fat versus fruits and vegetables.
AB  - The authors explored associations of social environment with dietary behavior
      among participants in the Eating for a Healthy Life study, a randomized, low-fat,
      high-fruit-and-vegetable dietary intervention trial in religious organizations.
      Data in this report are from baseline telephone surveys of 1,520 persons that
      assessed dietary behaviors (Fat- and Fiber-Related Diet Behavior Questionnaire)
      and social environment (Moos Group Environment Scale). After adjusting for
      demographic characteristics, higher scores on the Cohesion and Order/Organization
      subscales were associated with higher fruit/vegetable scores (indicating higher
      fruit and vegetable consumption). Higher scores on the Cohesion, Leader Support,
      and Order/Organization subscales were also associated with lower fat scores
      (indicating lower fat intake). Dietary behaviors within religious organizations
      may be related to positive perceptions of the social environment. These results
      support further exploration of the potential influence of religious
      organizations' social environment on health behaviors and its applicability to
      dietary change interventions.

PMID- 17456860
TI  - Can optical imaging assist in characterization of the onset of angiogenesis in
      developing hepatic metastases in mice livers?
AB  - Optical imaging currently can be used to characterize some of the early steps in
      the angiogenic pathway in vivo in animals. Liu and Matsui have provided valuable
      information in regard to the sequential changes in the origin and nature of newly
      formed blood vessels during progressive stages of growth of hepatic colorectal
      cancer metastases. The short-term challenge is to image cellular events that
      precede visible vessel formation and that occur during drug-induced vascular
      regression.

PMID- 17456861
TI  - The American board of radiology perspective on maintenance of certification: part
      IV--practice quality improvement for diagnostic radiology.

PMID- 17456862
TI  - Large field trial for lung cancer screening: putting the wrong cart before the
      horse?

PMID- 17456864
TI  - Evidence-based practice in radiology: step 5 (evaluate)--caveats and common
      questions.
AB  - So far, this series has described and illustrated the first four steps of the
      five-step evidence-based practice (EBP) process that was originally designed and
      taught by the medical epidemiologists of McMaster University (Hamilton, Ontario,
      Canada) and the National Health Service Centre for Evidence-Based Medicine
      (University of Oxford, Oxford, England). This article in the series first briefly
      considers the fifth step (evaluate). A more detailed consideration of caveats,
      common questions, and challenges relevant to EBP in radiology then follows. These
      are issues that merit some thought by those beginning or continuing work in EBP.

PMID- 17456865
TI  - Nano- and microparticle-based imaging of cardiovascular interventions: overview.
AB  - The rapid progress of nanoscience and the application of nanotechnology are
      changing the foundations of diagnosis, treatment, and prevention of
      cardiovascular diseases. As the core of nanotechnology, nano- and microparticles
      offer "three-in-one" functions as imaging agents, target probes, and therapeutic
      carriers. While nano- and microparticle-based imaging of cardiovascular
      interventions is still in its developing phase, it has already presented the
      exciting potential to monitor primary interventional procedures for precise
      therapeutic delivery, enhance the effectiveness of delivered therapeutics, and
      monitor therapeutic efficiency after interventions performed to treat
      cardiovascular diseases. This article provides an overview of the current status
      of the application of nano- and microparticles in the imaging of cardiovascular
      interventions.

PMID- 17456866
TI  - Breast cancer detection rate: designing imaging trials to demonstrate
      improvements.
AB  - PURPOSE: To estimate the extent of variability in screening mammography cancer
      detection rates and its effect on a hypothetical clinical trial of a new
      screening modality used to measure changes in cancer detection rate. MATERIALS
      AND METHODS: Each registry and the statistical coordinating center received
      institutional review board approval along with approval for consenting processes
      or a waiver of consent to enroll participants, link data, and perform analytic
      studies. This study was HIPAA compliant. The authors estimated the distribution
      of individual radiologists' breast cancer detection rates for 2,289,132 screening
      mammograms (9030 cancers) read by 510 radiologists in the United States who
      participated in the Breast Cancer Surveillance Consortium from 1996 through 2002.
      They then computed the distributions of breast cancer detection rates expected
      from a trial of screening mammography and multiple radiologists, as well as
      similar distributions for a hypothetical new modality that depicts one additional
      cancer per reader per 1000 screening examinations. Statistical power was
      calculated. RESULTS: The mean screening mammography cancer detection rate for
      individual radiologists was 3.91 cancers (standard deviation, 1.93; range, 0.25
      13.75) per 1000 examinations. To achieve 80% power to detect a hypothetical
      increase of one additional cancer detected per reader per 1000 screening
      examinations, a trial in which a new modality was compared with standard
      mammography would require at least 25 radiologists each reading the images of at
      least 8000 screening examinations or 91 radiologists each reading the images of
      1000-2000 examinations. CONCLUSION: The low breast cancer prevalence in an
      average-risk screening population and the large interradiologist variability in
      the observed cancer detection rate suggest that for new technologies to
      demonstrate significant improvement in cancer detection rate in a clinical trial,
      very large samples of both radiologists and patients will be required.

PMID- 17456867
TI  - Contrast-enhanced cardiac MR imaging in the detection of reduced coronary flow
      velocity reserve.
AB  - PURPOSE: To prospectively evaluate the accuracy of contrast material-enhanced
      cardiac magnetic resonance (MR) imaging for determining impaired coronary flow
      velocity reserve (CFR) by using Doppler flow measurement as the reference
      standard. MATERIALS AND METHODS: The study was approved by the institutional
      ethics committee, and all patients gave written informed consent. Eligible
      patients underwent contrast-enhanced cardiac MR imaging and invasive measurement
      of CFR. For contrast-enhanced MR imaging, a three-section single-shot saturation
      recovery gradient-recalled echo sequence with steady-state free precession was
      used. Sections were divided into six segments. For each segment, a transmural and
      subendocardial myocardial perfusion reserve index (MPRI) was calculated by using
      the upslope of the signal intensity-time curve during the first pass of contrast
      material at rest and during adenosine infusion (140 microg per kilogram body
      weight per minute). MPRIs of vascular regions were compared with the
      corresponding CFR. Receiver operating characteristic (ROC) analysis was performed
      to find the number of segments needed for best diagnostic accuracy of MPRI and to
      find a cutoff value for MPRI in the detection of a reduced CFR. RESULTS: Thirty
      five patients were evaluated (male-to-female ratio, 27:8; mean age +/- standard
      deviation, 63.5 years +/- 8.2; mean body mass index, 28.8 kg/m(2) +/- 3.8), and
      43 vascular regions were analyzed. A linear correlation was found between the
      MPRI and CFR (r = 0.44, P < .05). The MPRI was significantly lower in vascular
      regions with a CFR of less than 2.00 than in regions with a CFR of 2.00 or
      greater (P < .05). Detection of a CFR of less than 2.00 was more accurate with
      subendocardial MPRI measurements than with transmural measurements. The mean
      subendocardial MPRI of the segments with the three lowest MPRIs of a vascular
      region showed the best diagnostic performance in the detection of a CFR of less
      than 2.00 (area under the ROC curve, 0.85; sensitivity, 84%; specificity, 75%) by
      using a cutoff value of 1.21. CONCLUSION: The diagnostic accuracy of
      subendocardial perfusion analysis in contrast-enhanced cardiac MR imaging is
      higher than that of transmural analysis.

PMID- 17456868
TI  - Assessment of renal hemodynamics and function in pigs with 64-section
      multidetector CT: comparison with electron-beam CT.
AB  - PURPOSE: To prospectively evaluate the feasibility of obtaining reliable
      measurements of renal hemodynamics and function by using 64-section multidetector
      CT. MATERIALS AND METHODS: This study was approved by the Institutional Animal
      Care and Use Committee. Eight pigs (two with induced unilateral renal artery
      stenosis) were studied with both electron-beam CT and 64-section multidetector CT
      at 1-week intervals in randomized order. Both kidneys were scanned repeatedly,
      without table movement, for about 3 minutes after intravenous (IV) administration
      of a bolus of contrast medium and again during vasodilator challenge
      (acetylcholine). Images were reconstructed on each CT console but were analyzed
      on the same independent workstation. Attenuation changes in the kidneys were
      plotted as function of time, and time-attenuation curves (TACs) were subsequently
      analyzed to determine regional perfusion and volume, glomerular filtration rate
      (GFR), and renal blood flow (RBF). Statistical analysis utilized Student t test,
      analysis of variance (ANOVA), linear regression, and Bland-Altman analysis.
      RESULTS: TACs obtained with multidetector CT were qualitatively similar to those
      obtained with electron-beam CT, as were the quantitative values of renal
      perfusion and function. RBF correlated significantly between the two techniques
      (RBF(MD) = 0.96 . RBF(EB) mL/min; R = 0.77, P < .01). GFR(MD) was also similar to
      GFR(EB) (77.6 +/- 8.3 vs 79.8 +/- 8.8 mL/min, p > .05). Bland-Altman plots showed
      good agreement between the two techniques. Both techniques similarly detected the
      differences between stenotic and contralateral kidneys. CONCLUSION: The clinical
      multidetector CT scanner provides reliable measurements of single-kidney
      hemodynamics and function, which are similar to those obtained with previously
      validated electron-beam CT.

PMID- 17456869
TI  - Determining contrast medium dose and rate on basis of lean body weight: does this
      strategy improve patient-to-patient uniformity of hepatic enhancement during
      multi-detector row CT?
AB  - PURPOSE: To prospectively evaluate the use of lean body weight (LBW) as the main
      determinant of the volume and rate of contrast material administration during
      multi-detector row computed tomography of the liver. MATERIALS AND METHODS: This
      HIPAA-compliant study had institutional review board approval. All patients gave
      written informed consent. Four protocols were compared. Standard protocol
      involved 125 mL of iopamidol injected at 4 mL/sec. Total body weight (TBW)
      protocol involved 0.7 g iodine per kilogram of TBW. Calculated LBW and measured
      LBW protocols involved 0.86 g of iodine per kilogram and 0.92 g of iodine per
      kilogram calculated or measured LBW for men and women, respectively. Injection
      rate used for the three experimental protocols was determined proportionally on
      the basis of the calculated volume of contrast material. Postcontrast attenuation
      measurements during portal venous phase were obtained in liver, portal vein, and
      aorta for each group and were summed for each patient. Patient-to-patient
      enhancement variability in same group was measured with Levene test. Two-tailed t
      test was used to compare the three experimental protocols with the standard
      protocol. RESULTS: Data analysis was performed in 101 patients (25 or 26 patients
      per group), including 56 men and 45 women (mean age, 53 years). Average summed
      attenuation values for standard, TBW, calculated LBW, and measured LBW protocols
      were 419 HU +/- 50 (standard deviation), 443 HU +/- 51, 433 HU +/- 50, and 426 HU
      +/- 33, respectively (P = not significant for all). Levene test results for
      summed attenuation data for standard, TBW, calculated LBW, and measured LBW
      protocols were 40 +/- 29, 38 +/- 33 (P = .83), 35 +/- 35 (P = .56), and 26 +/- 19
      (P = .05), respectively. CONCLUSION: By excluding highly variable but poorly
      perfused adipose tissue from calculation of contrast medium dose, the measured
      LBW protocol may lessen patient-to-patient enhancement variability while
      maintaining satisfactory hepatic and vascular enhancement.

PMID- 17456870
TI  - Can high-attenuation renal cysts be differentiated from renal cell carcinoma at
      unenhanced CT?
AB  - PURPOSE: To retrospectively determine if renal cell carcinoma can be
      differentiated from high-attenuation renal cysts at unenhanced computed
      tomography (CT) based on Hounsfield unit measurements and heterogeneity.
      MATERIALS AND METHODS: The Human Investigation Committee at our institution
      approved this study with waiver of informed consent. This study was compliant
      with the HIPAA. Fifty-four pathologically proved renal cell carcinomas in 54
      patients (36 men and 18 women; average age, 53 years; range, 23-90 years) and 56
      high-attenuation renal cysts in 51 patients (30 men and 21 women; average age, 63
      years; range, 28-86 years) were retrospectively evaluated at unenhanced CT. Two
      independent readers reviewed randomized unenhanced CT images and obtained
      Hounsfield unit readings of each mass. A subjective determination of lesion
      heterogeneity was also performed by using a four-point scale (1: homogeneous, 2:
      mildly heterogeneous, 3: moderately heterogeneous, 4: markedly heterogeneous).
      Statistical analysis was performed by using Bland-Altman regression tree,
      classification and regression tree, and Shapiro-Wilk normality test. RESULTS: The
      average attenuation of cysts for reader 1 was 53.4 HU (range, 23-113 HU) and for
      reader 2 was 53.8 HU (range, 21-108 HU). The average attenuation of neoplasms for
      reader 1 was 34.7 HU (range, 21-60 HU) and for reader 2 was 38.4 HU (range, 22-60
      HU). For cyst heterogeneity, a score of 1 was given in 55 of 56 (98%) cysts for
      reader 1 and in 53 of 56 (95%) cysts for reader 2. For neoplasm heterogeneity, a
      score of 1 was given in 35 of 54 (65%) neoplasms for reader 1 and in 36 of 54
      (67%) for reader 2. Given the distribution of cyst and tumor attenuation values
      and lesion heterogeneity, a homogeneous mass measuring 70 HU or greater at
      unenhanced CT has a greater than 99.9% chance of representing a high-attenuation
      renal cyst. CONCLUSION: The findings from this study may help differentiate high
      attenuation renal cysts from renal cell carcinomas at unenhanced CT and may
      suggest the next appropriate imaging study for definitive characterization.

PMID- 17456871
TI  - Comparison of SPIO and USPIO for in vitro labeling of human monocytes: MR
      detection and cell function.
AB  - PURPOSE: To label human monocytes with superparamagnetic iron oxide (SPIO) and
      compare labeling efficiency with that of ultrasmall SPIO (USPIO) and evaluate the
      effect of iron incorporation on cell viability, migratory capacity, and
      proinflammatory cytokine production. MATERIALS AND METHODS: The study was
      approved by the institutional ethics committee; informed consent was obtained
      from donors. Freshly isolated human monocytes were labeled with iron particles of
      two sizes, USPIOs of 30 nm and SPIOs of 150 nm, for 1.5 hours in culture medium
      containing 0.1, 0.5, 1.0, and 3.7 mg of iron per milliliter. Labeling efficiency
      was determined with relaxation time magnetic resonance (MR) imaging (4.7 T) and
      Prussian blue staining for presence of intracellular iron. Cell viability was
      monitored; migratory capacity of monocytes after labeling was evaluated by using
      an in vitro assay with monolayers of brain endothelial cells. Levels of
      proinflammatory cytokines, interleukin (IL) 1 and IL-6, were measured with enzyme
      linked immunosorbent assay 24 hours after labeling. Data were analyzed with
      Student t test or two-way analysis of variance followed by a multiple-comparison
      procedure. RESULTS: R2 relaxation rates increased for cell samples incubated with
      SPIOs, whereas rates were not affected for samples incubated with highest
      concentration of USPIOs. Labeling monocytes with SPIOs (1.0 mg Fe/mL) resulted in
      an R2 of 13.1 sec(-1) +/- 0.8 (standard error of the mean) (7 sec(-1) +/- 0.2 for
      vehicle-treated cells, P < .05) and had no effect on cell viability. On the basis
      of T2 relaxation times, the in vitro MR detection limit of 58 labeled monocytes
      per 0.05 microL was calculated. Migration of labeled monocytes was not different
      from that of vehicle-treated cells. Intracellular iron had no effect on
      production of IL-1 and IL-6 24 hours after labeling. CONCLUSION: In vitro
      labeling of human monocytes is effective by using SPIOs, not USPIOs. Incubation
      with SPIOs (1.0 mg Fe/mL) results in efficient labeling detectable on MR images
      and does not affect cellular viability and activation markers such as cell
      migration and cytokine production.

PMID- 17456872
TI  - White matter damage in Alzheimer disease and mild cognitive impairment:
      assessment with diffusion-tensor MR imaging and parallel imaging techniques.
AB  - PURPOSE: To prospectively determine regional differences in fiber tract integrity
      between elderly patients with Alzheimer disease (AD), those with mild cognitive
      impairment (MCI), and healthy elderly subjects by using diffusion-tensor imaging
      with parallel imaging techniques and a new eight-element receiving coil.
      MATERIALS AND METHODS: Institutional review board approval and informed consent
      were obtained. Fifteen patients with AD (seven men, eight women; mean age; 68.8
      years), 16 patients with MCI (nine men, seven women; mean age, 68.9 years) and 19
      healthy control subjects (eight men, 11 women; mean age, 63.9 years) underwent
      diffusion-tensor imaging performed with a 1.5-T magnetic resonance system. An
      echo-planar imaging diffusion sequence was used with an integrated parallel
      acquisition technique (PAT) and an eight-element head coil. The mean apparent
      diffusion coefficient (ADC), fractional anisotropy (FA), and relative anisotropy
      (RA) values of several white matter (WM) regions were determined. The Kruskal
      Wallis test was used initially to test for overall equality of median values in
      each data group. Single posttest comparisons were performed with the Mann-Whitney
      U test, with an overall statistical significance level of .05. RESULTS: FA and RA
      values were significantly (P < .05) decreased, whereas ADC values in the splenium
      of the corpus callosum were higher in patients with AD than in patients with MCI.
      Evidence of higher ADC values in the WM of the temporal lobe was observed in
      patients with AD compared with the ADC values in patients with MCI and in control
      subjects. ADC values in the parietal WM were significantly (P < .05) elevated in
      patients with MCI compared with those in control subjects. The images obtained
      with integrated PAT showed fewer susceptibility artifacts and were less distorted
      than images acquired without parallel imaging techniques. CONCLUSION: Reduced FA
      and RA values in patients with AD suggest that diffusion-tensor imaging of the
      brain can be used to confirm clinical manifestation of AD but is less applicable
      in the detection of MCI.

PMID- 17456873
TI  - Inoperable hepatocellular carcinoma: transarterial 188Re HDD-labeled iodized oil
      for treatment--prospective multicenter clinical trial.
AB  - PURPOSE: To prospectively evaluate, in a multicenter clinical trial, dosimetry
      guided transarterial radionuclide therapy (TART) with rhenium 188 ((188)Re) 4
      hexadecyl 1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol (HDD)-labeled iodized
      oil in inoperable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Ninety
      three patients were recruited from 2000 to 2005 for this ethics committee
      approved study. Informed written consent was obtained. After complete clinical
      evaluation (including assessment of liver status, serum alpha-fetoprotein [AFP]
      level, tumor size, portal vein status, Child-Pugh classification, Okuda staging),
      radiation absorbed dose (RAD) to various organs, including tumor, was calculated
      after injecting 185 MBq of (188)Re HDD iodized oil via the hepatic artery. From
      this value, the maximum tolerable activity of (188)Re, defined as the amount of
      radioactivity delivering no more than 12 Gy of RAD to lungs, 30 Gy to normal
      liver, or 1.5 Gy to bone marrow, was calculated and injected. RESULTS: Mean
      patient age was 53 years (80 men and 13 women). Sixty-eight percent of patients
      had serologic evidence of hepatitis B and/or C; 40% had clinicoradiologic
      evidence of cirrhosis. Mean tumor diameter was 10.3 cm +/- 4.4, with 40% of
      patients having more than three lesions; in 50% of patients, tumor was either
      unilateral, occupying 50% or more of the liver, or bilateral. AFP was elevated in
      68% of patients and was elevated to more than 300 ng/mL in 44% of patients. There
      was portal vein thrombosis in 38% of patients, Child-Pugh status B disease in 37%
      of patients, and Okuda stage II or III disease in 50% of patients. Mean first
      administered activity was 5.3 GBq +/- 1.6, which delivered 88 Gy of RAD to the
      tumor. Treatment was tolerated well. Of 66 patients in whom complete tumor
      response occurred, five (8%) had complete tumor mass ablation, 17 (26%) had a
      partial response (>50% tumor reduction), and 23 (35%) had stable disease. Only
      RAD to the tumors was found to be significantly (P = .001) associated with tumor
      and/or AFP response. Survival rates at 6, 9, 12, 24, and 36 months among patients
      with objective tumor response were 100%, 95%, 90%, 58%, and 30%, respectively,
      with a median survival of 980 days. CONCLUSION: TART appears to be a safe,
      effective, and promising therapeutic option in patients with inoperable HCC.

PMID- 17456874
TI  - Suspected appendicitis in children: rectal and intravenous contrast-enhanced
      versus intravenous contrast-enhanced CT.
AB  - PURPOSE: To retrospectively compare the diagnostic performance of intravenous
      contrast material-enhanced computed tomography (CT) with that of intravenous and
      rectal contrast-enhanced CT in the evaluation of children suspected of having
      appendicitis by using pathologic findings, surgical findings, or a follow-up
      telephone call as the reference standard. MATERIALS AND METHODS: This HIPAA
      compliant study was approved by the committee on clinical investigations. As part
      of a larger study, informed consent was obtained from all parents and from all
      children older than 7 years. Consecutive patients aged 5-21 years who presented
      to the emergency department and were suspected of having appendicitis were
      studied with CT. From April 2003 until February 2004, patients underwent
      intravenous and rectal contrast-enhanced CT. From March 2004 until December 2004,
      patients underwent intravenous contrast-enhanced CT. Demographic data, clinical
      outcomes, and test performance characteristics--including sensitivity,
      specificity, accuracy, and negative and positive predictive values--were
      compared. RESULTS: Of the 416 patients who met inclusion criteria, 223 underwent
      intravenous and rectal contrast-enhanced CT and 193 underwent intravenous
      contrast-enhanced CT. There were no differences in sex distribution (55% vs 52%
      male patients), frequency of appendicitis (36% vs 32%), or frequency of equivocal
      CT findings (4%) between the groups. Intravenous and rectal contrast-enhanced CT
      had a sensitivity of 92% (95% confidence interval [CI]: 85%, 97%), a specificity
      of 87% (95% CI: 79%, 92%), a negative predictive value of 94% (95% CI: 90%, 98%),
      and an accuracy of 89% (95% CI: 85%, 93%). Intravenous contrast-enhanced CT had a
      sensitivity of 93% (95% CI: 84%, 97%), a specificity of 92% (95% CI: 85%, 96%), a
      negative predictive value of 95% (95% CI: 90%, 99%), and an accuracy of 92% (95%
      CI: 88%, 96%) (P > .2 for all comparisons). CONCLUSION: There was no significant
      difference between the performance of intravenous contrast-enhanced CT and that
      of rectal and intravenous contrast-enhanced CT in children suspected of having
      appendicitis.

PMID- 17456875
TI  - Coronary artery calcium: a multi-institutional, multimanufacturer international
      standard for quantification at cardiac CT.
AB  - PURPOSE: To develop a consensus standard for quantification of coronary artery
      calcium (CAC). MATERIALS AND METHODS: A standard for CAC quantification was
      developed by a multi-institutional, multimanufacturer international consortium of
      cardiac radiologists, medical physicists, and industry representatives. This
      report specifically describes the standardization of scan acquisition and
      reconstruction parameters, the use of patient size-specific tube current values
      to achieve a prescribed image noise, and the use of the calcium mass score to
      eliminate scanner- and patient size-based variations. An anthropomorphic phantom
      containing calibration inserts and additional phantom rings were used to simulate
      small, medium-size, and large patients. The three phantoms were scanned by using
      the recommended protocols for various computed tomography (CT) systems to
      determine the calibration factors that relate measured CT numbers to calcium
      hydroxyapatite density and to determine the tube current values that yield
      comparable noise values. Calculation of the calcium mass score was standardized,
      and the variance in Agatston, volume, and mass scores was compared among CT
      systems. RESULTS: Use of the recommended scanning parameters resulted in similar
      noise for small, medium-size, and large phantoms with all multi-detector row CT
      scanners. Volume scores had greater interscanner variance than did Agatston and
      calcium mass scores. Use of a fixed calcium hydroxyapatite density threshold (100
      mg/cm(3)), as compared with use of a fixed CT number threshold (130 HU), reduced
      interscanner variability in Agatston and calcium mass scores. With use of a
      density segmentation threshold, the calcium mass score had the smallest variance
      as a function of patient size. CONCLUSION: Standardized quantification of CAC
      yielded comparable image noise, spatial resolution, and mass scores among
      different patient sizes and different CT systems and facilitated reduced
      radiation dose for small and medium-size patients.

PMID- 17456876
TI  - Intraaxial brain masses: MR imaging-based diagnostic strategy--initial
      experience.
AB  - PURPOSE: To develop and retrospectively determine the accuracy of a magnetic
      resonance (MR) imaging strategy to differentiate intraaxial brain masses, with
      histologic findings or clinical diagnosis as the reference standard. MATERIALS
      AND METHODS: The study was HIPAA compliant and was approved by the institutional
      review board. A waiver of informed consent was obtained. A strategy was developed
      on the basis of conventional MR imaging, diffusion-weighted MR imaging, perfusion
      MR imaging, and proton MR spectroscopy to classify intraaxial masses as low-grade
      primary neoplasms, high-grade primary neoplasms, metastatic neoplasms, abscesses,
      lymphomas, tumefactive demyelinating lesions (TDLs), or encephalitis. The
      strategy was evaluated by using data from 111 patients (46 women, 65 men; mean
      age, 48.9 years) with imaging results available on a departmental picture
      archiving and communication system from a 5-year search period. Bayesian
      statistics of the strategy elements and three clinical tasks were calculated.
      RESULTS: Search results identified 44 patients with high-grade and 14 with low
      grade primary neoplasms, 24 with abscesses, 12 with lymphoma, 11 with TDLs, five
      with metastases, and one with encephalitis who had undergone conventional and
      advanced MR imaging. However, only 40 patients (25 women, 15 men; mean age, 45
      years) had undergone all studies and had data to allow completion of the entire
      strategy. Accuracy, sensitivity, and specificity of the strategy, respectively,
      were 90%, 97%, and 67% for discrimination of neoplastic from nonneoplastic
      diseases, 90%, 88%, and 100% for discrimination of high-grade from low-grade
      neoplasms, and 85%, 84%, and 87% for discrimination of high-grade neoplasms and
      lymphoma from low-grade neoplasms and nonneoplastic diseases. CONCLUSION: An
      integrated MR imaging-based strategy, which is accurate in differentiation of
      several intraaxial brain masses, was proposed.

PMID- 17456877
TI  - Teniae coli-based circumferential localization system for CT colonography:
      feasibility study.
AB  - This HIPAA-compliant study, with institutional review board approval and informed
      patient consent, was conducted to retrospectively develop a teniae coli-based
      circumferential localization method for guiding virtual colon navigation and
      colonic polyp registration. Colonic surfaces (n = 72) were depicted at computed
      tomographic (CT) colonography performed in 36 patients (26 men, 10 women; age
      range, 47-72 years) in the supine and prone positions. For 70 (97%) colonic
      surfaces, the tenia omentalis (TO), the most visible of the three teniae coli on
      a well-distended colonic surface, was manually extracted from the cecum to the
      descending colon. By virtually dissecting and flattening the colon along the TO,
      the authors developed a localization system involving 12 grid lines to estimate
      the circumferential positions of polyps. A sessile polyp would most likely (at
      95% confidence level) be found within +/-1.2 grid lines (one grid line equals
      1/12 the circumference) with use of the proposed method. By orienting and
      positioning the virtual cameras with use of the new localization system,
      synchronized prone and supine navigation was achieved. The teniae coli are
      extractable landmarks, and the teniae coli-based circumferential localization
      system helps guide virtual navigation and polyp registration at CT colonography.

PMID- 17456878
TI  - Pulmonary nodules: sensitivity of maximum intensity projection versus that of
      volume rendering of 3D multidetector CT data.
AB  - PURPOSE: To prospectively compare maximum intensity projection (MIP) and volume
      rendering (VR) of multidetector computed tomographic (CT) data for the detection
      of small intrapulmonary nodules. MATERIALS AND METHODS: This institutional review
      board-approved prospective study included 20 oncology patients (eight women and
      12 men; mean age, 56 years +/- 16 [standard deviation]) who underwent clinically
      indicated standard-dose thoracic multidetector CT and provided informed consent.
      Transverse thin slabs of the chest (thickness, 7 mm; reconstruction increment,
      3.5 mm) were created by using MIP and VR techniques to reconstruct CT data
      (collimation, 16 x 0.75 mm) and were reviewed in interactive cine mode. Mean,
      minimum, and maximum reading time per examination and per radiologist was
      documented. Three radiologists digitally annotated all nodules seen in a way that
      clearly determined their locations. The maximum number of nodules detected by the
      three observers and confirmed by consensus served as the reference standard.
      Descriptive statistics were calculated, with P < .05 indicating a significant
      difference. The Wilcoxon matched-pairs signed rank test and confidence intervals
      for differences between methods were used to compare the sensitivities of the two
      methods. RESULTS: VR performed significantly better than MIP with regard to both
      detection rate (P < .001) and reporting time (P < .001). The superiority of VR
      was significant for all three observers and for nodules smaller than 11 mm in
      diameter and was pronounced for perihilar nodules (P = .023). Sensitivities
      achieved with VR ranged from 76.5% to 97.3%, depending on nodule size.
      CONCLUSION: VR is the superior reading method compared with MIP for the detection
      of small solid intrapulmonary nodules.

PMID- 17456881
TI  - Case 112: pituitary stalk transection syndrome with ectopic posterior pituitary
      gland.

PMID- 17456882
TI  - Case 113: pancreatic cystosis.

PMID- 17456883
TI  - The inverted Napoleon's hat sign.

PMID- 17456884
TI  - Mammography and fetal dose.

PMID- 17456885
TI  - Contrast material-induced nephropathy.

PMID- 17456886
TI  - Pancreatic cysts 3 cm or smaller.

PMID- 17456887
TI  - Salami science.

PMID- 17456888
TI  - Effects of an extended version of the lee silverman voice treatment on voice and
      speech in Parkinson's disease.
AB  - PURPOSE: The present study examined vocal SPL, voice handicap, and speech
      characteristics in Parkinson's disease (PD) following an extended version of the
      Lee Silverman Voice Treatment (LSVT), to help determine whether current treatment
      dosages can be altered without compromising clinical outcomes. METHOD: Twelve
      participants with idiopathic PD received the extended treatment version (LSVT-X),
      similar to LSVT except that it was administered twice a week in 1-hr sessions
      over 8 weeks and required substantially more home practice. Recordings were made
      in a sound-treated booth immediately before and after treatment, and again 6
      months later. Vocal SPL was measured for 4 different tasks and compared with data
      from a previous study, in which participants with PD received traditional LSVT 4
      times a week for 4 weeks. Listener ratings were conducted with audio samples from
      both studies, using sentence pairs from a standard passage. LSVT-X participants
      completed the Voice Handicap Index (VHI) before each set of recordings. RESULTS:
      Participants receiving LSVT-X significantly increased vocal SPL by 8 dB after
      treatment and maintained increased vocal SPL by 7.2 dB at 6 months. VHI scores
      improved for 25% of the LSVT-X participants following treatment, and listener
      ratings indicated audible improvement in speech. CONCLUSIONS: LSVT-X successfully
      increased vocal SPL (which was consistent with improvements following traditional
      LSVT), decreased perceived voice handicap, and improved functional speech in
      individuals with PD. Further large-scale research is required to truly establish
      LSVT-X efficacy.

PMID- 17456889
TI  - Speech and language skills of parents of children with speech sound disorders.
AB  - PURPOSE: This study compared parents with histories of speech sound disorders
      (SSD) to parents without known histories on measures of speech sound production,
      phonological processing, language, reading, and spelling. Familial aggregation
      for speech and language disorders was also examined. METHOD: The participants
      were 147 parents of children with SSD (58 fathers and 89 mothers) who were
      directly tested and interviewed for family history of disorders. RESULTS: Thirty
      six parents (18 mothers and 18 fathers) reported enrollment in speech therapy as
      children for SSD. Parents with a history of speech therapy obtained lower scores
      on the Multisyllabic Word Repetition, Nonword Repetition, and Tongue Twister
      tasks than parents without such histories. These parents also had poorer reading,
      spelling, and receptive language skills. Parents with histories of SSD and
      additional language impairments (LI) performed worse than parents with isolated
      SSD on all measures except Pig Latin and oral motor skills. Familial aggregation
      for SSD and LI was supported. In addition, the likelihood of SSD in a family
      member increased by a factor of 1.9 over rates of SSD found in individuals
      without additional family members with SSD, and the odds of LI increased by a
      factor of 4.1 over rates of LI found in individuals without additional family
      members with LI for each additional family member with SSD or LI, respectively.
      CONCLUSIONS: The results documented both residual effects in adulthood of
      childhood SSD and familial aggregation for SSD. These residual difficulties do
      not appear to affect educational and occupational outcomes.

PMID- 17456890
TI  - Clinician-child interactions: adjustments in linguistic complexity.
AB  - PURPOSE: This pilot study examined the extent and nature of associations in the
      linguistic complexity used by child and clinician within conversational
      interactions. METHOD: Correlation analyses focused on semantic and
      morphosyntactic language sample measures from an experienced speech-language
      clinician and 29 children with language impairment. RESULTS: Positive
      associations emerged between a variety of child and clinician measures, even when
      the effect of child age was removed. The most robust effect related to clinician
      adjustments in both morphosyntactic complexity and vocabulary diversity
      associated with differences in children's developmental sentence scores.
      CONCLUSIONS: Within a conversational exchange, the clinician in this study made
      significant adjustments in her linguistic complexity that were due, at least in
      part, to the linguistic complexity used by the children with whom she was
      interacting. Associations were similar to adjustments reported in prior studies
      of parent and teacher interactions with children with differing language
      abilities. However, the extent to which these findings generalize to other
      clinicians needs to be examined. Results from the present study challenge
      clinicians to dedicate conscious thought toward how their linguistic input should
      be structured, taking into consideration both the goal of the interaction and
      each child's profile of linguistic strengths and weaknesses. Directions for
      future research are also provided.

PMID- 17456891
TI  - The use of ultrasound in remediation of North American English /r/ in 2
      adolescents.
AB  - PURPOSE: Ultrasound can provide images of the tongue during speech production.
      The present study set out to examine the potential utility of ultrasound in
      remediation of North American English /r/. METHOD: The participants were 2
      Canadian English-speaking adolescents who had not yet acquired /r/. The study
      included an initial period without ultrasound and 13 treatment sessions, each 1
      hr long, using ultrasound. Speech samples were recorded at screening and
      immediately before and after treatment. Samples were analyzed acoustically and
      with listener judgments. Ultrasound images were obtained before, during, and
      after the treatment period. RESULTS: Three speech-language pathologists
      unfamiliar with the participants rated significantly more posttreatment tokens as
      accurate [r]s in single words and some phrases. Acoustic analyses showed an
      expected lowering of the third formant after treatment. A qualitative observation
      of posttreatment ultrasound images for accurate [r] tokens showed tongue shapes
      to be more similar to those of typical adults than had been observed before
      treatment. Participants needed continued practice of their newly acquired skills
      in sentences and conversation. CONCLUSION: Two-dimensional dynamic ultrasound
      appears to have potential utility for remediation of /r/ in speakers with
      residual /r/ impairment. Further research is needed with larger numbers of
      participants to establish the relative efficacy of ultrasound in treatment.

PMID- 17456892
TI  - Effects of verbal cue on bolus flow during swallowing.
AB  - PURPOSE: To examine the effects of verbal cuing to initiate swallowing on bolus
      flow measures in healthy adults. METHOD: Videofluoroscopic examinations were
      completed in 12 healthy older adults (median age=69 years) as they swallowed 5 ml
      of self-administered liquid barium in 2 conditions: verbally cued and noncued
      swallows. In the cued condition, participants held the liquid in their mouths
      until instructed to swallow. In the noncued condition, participants swallowed in
      their usual manner. RESULTS: Verbal cue affected bolus position at onset of
      timing measures, thereby influencing duration. The bolus was positioned more
      posterior in the oral cavity at onset of oral transit for cued as compared with
      noncued swallows. The leading edge of the bolus at onset of the pharyngeal
      swallow was more superior in the pharynx for cued as compared with noncued
      swallows. Durations of the cued swallows were significantly shorter than for
      noncued swallows for all timing measures. Bolus direction scores were not
      significantly different between conditions. CONCLUSIONS: Findings suggest that
      swallowing is altered by the use of verbal cues to initiate swallowing in healthy
      adults. Determining whether shorter durations with implementation of verbal cues
      are evident in individuals with dysphagia and whether effects are beneficial or
      deleterious requires continued research.

PMID- 17456893
TI  - Tongue measures in individuals with normal and impaired swallowing.
AB  - PURPOSE: This investigation sought to add to the extant literature on measures of
      normal tongue function, to provide information on measures of tongue function in
      a group of individuals with oral phase dysphagia, and to provide a comparison of
      these 2 groups matched for age and gender. METHOD: The Iowa Oral Performance
      Instrument was utilized to measure tongue function (strength and endurance) in a
      group of individuals with normal (N=200) and impaired (N=50) swallowing. The peak
      measure of 3 encouraged trials was recorded as participants' strength, and 50% of
      their peak was sustained as long as possible for endurance. RESULTS: Results for
      the control group supported previous investigations wherein greater tongue
      strength was found in males than in females and in the youngest versus oldest
      groups. The experimental group demonstrated a similar trend in strength for
      gender. When matched for age and gender, the experimental group demonstrated
      significantly lower strength. Significant differences were not revealed on
      measures of tongue endurance. CONCLUSIONS: We were able to extend the normative
      database on tongue function and document reduced tongue strength in a group of
      individuals with dysphagia. The findings provide evidence that in this group,
      tongue weakness coincided with signs of dysphagia, adding justification for
      tongue-strengthening protocols.

PMID- 17456894
TI  - African American English dialect and performance on nonword spelling and phonemic
      awareness tasks.
AB  - PURPOSE: To evaluate the role of dialect on phonemic awareness and nonword
      spelling tasks. These tasks were selected for their reliance on phonological and
      orthographic processing, which may be influenced by dialect use. METHOD: Eighty
      typically developing African American children in Grades 1 and 3 were first
      screened for dialect use and then completed a standardized test of phonological
      processing and a nonword spelling measure. The influence of dialect was analyzed
      in both experimental tasks, followed by a qualitative analysis of dialect use in
      nonword spellings. RESULTS: Dialect density measures based solely on the use of
      African American English (AAE) phonological features explained few differences in
      phonological processing scores. In contrast, correlations indicated that children
      with higher dialect densities produced more nonword spelling errors influenced by
      AAE, an effect most evident in Grade 3. Qualitative analyses revealed AAE
      phonological features occurring in many of the misspelled nonwords. CONCLUSION:
      After Grade 2, nonword spelling may be more sensitive to the effects of dialect
      variation than are phonemic awareness tasks. It is suggested that spelling may be
      a more sensitive clinical indicator of difficulties in integrating the
      phonological and orthographic information needed for fluent decoding skill.

PMID- 17456895
TI  - Genetic etiology in cases of recovered and persistent stuttering in an
      unselected, longitudinal sample of young twins.
AB  - PURPOSE: The contribution of genetic factors in the persistence of and early
      recovery from stuttering was assessed. METHOD: Data from the Twins Early
      Development Study were employed. Parental reports regarding stuttering were
      collected at ages 2, 3, 4, and 7 years, and were used to classify speakers into
      recovered and persistent groups. Of 12,892 children with at least 2 ratings, 950
      children had recovered and 135 persisted in their stutter. RESULTS: Logistic
      regressions showed that the rating at age 2 was not predictive of later
      stuttering, whereas ratings at ages 3 and 4 were. Concordance rates were
      consistently higher for monozygotic than for dizygotic twin pairs (with the
      exception of girls at age 3). At 3, 4, and 7 years, the liability to stuttering
      was highly heritable (h2 estimates of between .58 and .66). Heritability for the
      recovered and persistent groups was also high but did not differ from each other.
      CONCLUSION: Stuttering appears to be a disorder that has high heritability and
      little shared environment effect in early childhood and for recovered and
      persistent groups of children, by age 7. The clinical implications of the
      findings are discussed.

PMID- 17456896
TI  - Peer conflict explanations in children, adolescents, and adults: examining the
      development of complex syntax.
AB  - PURPOSE: Expository discourse, the use of language to convey information,
      requires facility with complex syntax. Although expository discourse is often
      employed in school and work settings, little is known about its development in
      children, adolescents, and adults. Hence, it is difficult to evaluate this genre
      in students who have language disorders. This study examined syntactic complexity
      in expository discourse in an effort to begin to establish a normative database.
      METHOD: Speakers with typical development whose mean ages were 11, 17, and 25
      years old (n=60) participated in a peer conflict resolution (PCR) task designed
      to elicit expository discourse. The results were compared with an additional
      measure of expository discourse, the favorite game or sport (FGS) task, reported
      in a previous study that included these same participants (M. A. Nippold, L. J.
      Hesketh, J. K. Duthie, & T. C. Mansfield, 2005). RESULTS: The PCR task elicited
      expository discourse from speakers in all 3 groups. Older speakers packed more
      information into their utterances than did younger ones, and the PCR task
      elicited greater syntactic complexity than did the FGS task. CONCLUSIONS: The PCR
      task is potentially a useful tool for examining expository discourse. Research is
      needed to expand the database and administer the task to clinical groups.

PMID- 17456897
TI  - Quantitation of isoprostane isomers in human urine from smokers and nonsmokers by
      LC-MS/MS.
AB  - A simple, rapid liquid chromatography-tandem mass spectrometry method was
      developed to identify and quantitate in human urine the isoprostanes iPF(2 alpha)
      III, 15-epi-iPF(2 alpha)-III, iPF(2 alpha)-VI, and 8,12-iso-iPF(2 alpha)-VI along
      with the prostaglandin PGF(2 alpha) and 2,3-dinor-iPF(2 alpha)-III, a metabolite
      of iPF(2 alpha)-III. Assay specificity, linearity, precision, and accuracy met
      the required criteria for most analytes. The urine sample storage stability and
      standard solution stability were also tested. The methodology was applied to
      analyze 24 h urine samples collected from smokers and nonsmokers on controlled
      diets. The results for iPF(2 alpha)-III obtained by our method were significantly
      correlated with results by an ELISA, although an approximately 2-fold high bias
      was observed for the ELISA data. For iPF(2 alpha)-III and its metabolite 2,3
      dinor-iPF(2 alpha)-III, smokers had significantly higher concentrations than
      nonsmokers (513 +/- 275 vs. 294 +/- 104 pg/mg creatinine; 3,030 +/- 1,546 vs.
      2,046 +/- 836 pg/mg creatinine, respectively). The concentration of iPF(2 alpha)
      VI tended to be higher in smokers than in nonsmokers; however, the increase was
      not statistically significant in this sample set. Concentrations of the other
      three isoprostane isomers showed no trends toward differences between smokers and
      nonsmokers. Among smokers, the daily output of two type VI isoprostanes showed a
      weak correlation with the amount of tobacco smoke exposure, as determined by
      urinary excretion of total nicotine equivalents.

PMID- 17456898
TI  - SREBP-1-independent regulation of lipogenic gene expression in adipocytes.
AB  - Sterol regulatory element-binding protein (SREBP)-1c is now well established as a
      key transcription factor for the regulation of lipogenic enzyme genes such as FAS
      in hepatocytes. Meanwhile, the mechanisms of lipogenic gene regulation in
      adipocytes remain unclear. Here, we demonstrate that those in adipocytes are
      independent of SREBP-1c. In adipocytes, unlike in hepatocytes, the stimulation of
      SREBP-1c expression by liver X receptor agonist does not accompany lipogenic gene
      upregulation, although nuclear SREBP-1c protein is concomitantly increased,
      indicating that the activation process of SREBP-1c by the cleavage system is
      intact in adipocytes. Supportively, transcriptional activity of the mature form
      of SREBP-1c for the FAS promoter was negligible when measured by reporter
      analysis. As an underlying mechanism, accessibility of SREBP-1c to the functional
      elements was involved, because chromatin immunoprecipitation assays revealed that
      SREBP-1c does not bind to the functional SRE/E-box site on the FAS promoter in
      adipocytes. Moreover, genetic disruption of SREBP-1 did not cause any changes in
      lipogenic gene expression in adipose tissue. In summary, in adipocytes, unlike in
      hepatocytes, increments in nuclear SREBP-1c are not accompanied by
      transactivation of lipogenic genes; thus, SREBP-1c is not committed to the
      regulation of lipogenesis.

PMID- 17456899
TI  - The transfer of VLDL-associated phospholipids to activated platelets depends upon
      cytosolic phospholipase A2 activity.
AB  - We previously reported that VLDL could transfer phospholipids (PLs) to activated
      platelets. To identify the metabolic pathway involved in this process, the
      transfer of radiolabeled PLs from VLDL (200 microM PL) to platelets (2 x
      10(8)/ml) was measured after incubations of 1 h at 37 degrees C, with or without
      thrombin (0.1 U/ml) or LPL (500 ng/ml), in the presence of various inhibitors,
      including aspirin, a cyclooxygenase inhibitor (300 microM); esculetin, a 12
      lipoxygenase inhibitor (20 microM); methyl-arachidonyl-fluorophosphonate (MAFP),
      a phospholipase A(2) (PLA(2)) inhibitor (100 microM); 1,2-bis(2
      aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl) ester
      (BAPTA-AM), a Ca(2+) chelator (20 microM); bromoenol lactone (BEL), a Ca(2+)-
      independent phospholipase A(2) (iPLA(2)) inhibitor (100 nM); and 1-[6-[[17beta-3
      methoxyestra-1,3,5(10)-trien-17-yl-]amino]hexyl]1H-pyrrole-2,5-dione (U73122), a
      phospholipase C (PLC) inhibitor (20 microM). Aspirin and esculetin had no effect,
      showing that PL transfer was not dependent upon cyclooxygenase or lipoxygenase
      pathways. The transfer of PL was inhibited by MAFP, U73122, and BAPTA-AM.
      Although MAFP inhibited both cytosolic phospholipase A(2) (cPLA(2)) and iPLA(2),
      only cPLA(2) is a calcium-dependent enzyme. Because calcium mobilization is
      favored by PLC and inhibited by BAPTA-AM, the transfer of PL from VLDL to
      platelets appeared to result from a cPLA(2)-dependent process. The inhibition of
      iPLA(2) by BEL had no effect on PL transfers.

PMID- 17456901
TI  - The staying power of pain. A comparison of torture survivors from Bosnia and
      Colombia and their rates of anxiety, depression and PTSD.
AB  - The article describes symptoms of anxiety, depression and PTSD among Bosnian
      (n=17) and Colombian (n=17) torture survivors served by the Florida Center for
      Survivors of Torture, a programme of Gulf Coast Jewish Family Services, Inc.
      Information from clients enrolled in the programme for six months or more was
      collated over a 14 month period in order to better prioritize and design services
      for the two distinct populations. On average, the Bosnians in this sample
      experienced torture approximately 14 years ago while the Colombians'experience
      was approximately six years ago. Types of torture experienced by clients are
      documented using HURIDOCS and the number of family and friends affected by
      extreme trauma are counted. Employment and education levels attained are also
      identified. Findings show that 100% of Bosnians are symptomatic for depression
      and over half possess symptoms of PTSD compared to 35% of Colombians for
      depression and 18% for PTSD, despite the differences in years since trauma
      occurred. High incidences of torture experienced by Bosnian clients and high
      numbers of family and friends affected support the high rates of symptoms. For
      the Colombian clients, high rates of employment and years of education, as well
      as earlier intervention, may contribute to their lower rates of symptoms. The two
      client groups are distinguished by the unique circumstances experienced by each,
      including punctuated wartime versus a prolonged insurgency, as well as the
      refugee versus asylum seeker experience. This exploratory project informs the
      torture treatment model while recognizing the importance of ethnic, political and
      cultural perspectives affecting the healing process.

PMID- 17456900
TI  - Sex-specific regulation of gene expression in the aging monkey aorta.
AB  - Although increased vascular stiffness is more prominent in aging males than
      females, and males are more prone to vascular disease with aging, no study has
      investigated the genes potentially responsible for sex differences in vascular
      aging. We tested the hypothesis that the transcriptional adaptation to aging
      differs in males and females using a monkey model, which is not only
      physiologically and phylogenetically closer to humans than the more commonly
      studied rodent models but also is not afflicted with the most common forms of
      vascular disease that accompany the aging process in humans, e.g.,
      atherosclerosis, hypertension, and diabetes. The transcriptional profile of the
      aorta was compared by high-density microarrays between young and old males or
      females (n = 6/group). About 600 genes were expressed differentially when
      comparing old versus young animals. Surprisingly, <5% of these genes were shared
      between males and females. Radical differences between sexes were especially
      apparent for genes regulating the extracellular matrix, which relates to
      stiffness. Aging males were also more prone than females to genes switching
      smooth muscle cells from the "contractile" to "secretory" phenotype. Other sex
      differences involved genes participating in DNA repair, stress response, and cell
      signaling. Therefore, major differences of gene regulation exist between males
      and females in vascular aging, which may underlie the physiological differences
      characterizing aging arteries in males and females. Furthermore, the analyses in
      young monkeys demonstrated differences in genes regulating vascular structure,
      implying that the sex differences in vascular stiffness that develop with aging
      are programmed at an early age.

PMID- 17456902
TI  - Treatment of torture victims--a longitudinal clinical study.
AB  - AIM: To look at the effect of physiotherapy as part of the multidisciplinary
      treatment of torture victims. METHODS: Monitoring of an extended, personally
      designed, multidisciplinary treatment of 21 torture victims, earlier exposed to
      both physical and psychological torture, over nine months with assessment of
      outcome. The physiotherapy comprised elements such as massage, exercise on land,
      balance training and stimulation of proprioception, all aiming at regaining body
      awareness. Effect of treatment was measured using the fibrositis index. Non
      parametric statistics using the Wilcoxon test was applied. RESULTS: Prior to
      treatment the median score of the fibrositis index was 15 points (range 2-34).
      After nine months of multidisciplinary treatment the median score of the
      fibrositis index was 2 points (range 0-3415). This decrease in experienced muscle
      pain was statistically significant (p<0,0001). CONCLUSION: A high percentage of
      the torture victims in our study suffered from fibromyalgia prior to treatment. A
      multidisciplinary treatment involving individualised physiotherapy and
      psychotherapy had a significant effect on musculoskeletal pain in torture
      victims. Following nine months of treatment, only one torture victim in our study
      could be classified as suffering from fibromyalgia when applying the fibrositis
      index.

PMID- 17456903
TI  - Documentation of torture victims. Implementation of medico-legal protocols.
AB  - This article outlines the background for performing medical documentation in the
      context of a rehabilitation centre by reviewing literature and current practices.
      The article moreover delineates 6 ways of using medico-legal documentation in
      torture prevention: National legal proceedings; international legal proceedings;
      asylum cases; research, lobbying and advocacy activities. This article forms the
      basis for a Pilot Study performed at the Rehabilitation and Research Centre for
      Torture Victims in Copenhagen, which is described elsewhere.

PMID- 17456904
TI  - Impunity or immunity: wartime male rape and sexual torture as a crime against
      humanity.
AB  - This paper seeks to analyze the phenomenon of wartime rape and sexual torture of
      Croatian and Iraqi men and to explore the avenues for its prosecution under
      international humanitarian and human rights law. Male rape, in time of war, is
      predominantly an assertion of power and aggression rather than an attempt on the
      part of the perpetrator to satisfy sexual desire. The effect of such a horrible
      attack is to damage the victim's psyche, rob him of his pride, and intimidate
      him. In Bosnia- Herzegovina, Croatia, and Iraq, therefore, male rape and sexual
      torture has been used as a weapon of war with dire consequences for the victim's
      mental, physical, and sexual health. Testimonies collected at the Medical Centre
      for Human Rights in Zagreb and reports received from Iraq make it clear that
      prisoners in these conflicts have been exposed to sexual humiliation, as well as
      to systematic and systemic sexual torture. This paper calls upon the
      international community to combat the culture of impunity in both dictator-ruled
      and democratic countries by bringing the crime of wartime rape into the
      international arena, and by removing all barriers to justice facing the victims.
      Moreover, it emphasizes the fact that wartime rape is the ultimate humiliation
      that can be inflicted on a human being, and it must be regarded as one of the
      most grievous crimes against humanity. The international community has to
      consider wartime rape a crime of war and a threat to peace and security. It is in
      this respect that civilian community associations can fulfill their duties by
      encouraging victims of male rape to break their silence and address their socio
      medical needs, including reparations and rehabilitation.

PMID- 17456905
TI  - Torture in Egypt.
AB  - This article is concerned with the increasing prevalence of torture in Egypt.
      Torture is a widespread problem in Egypt, being practiced in the majority of
      police stations and state security places. It has become a routine practice and
      is seen daily on a systematic basis. The number of people who are subjected every
      month to torture is unimaginable. In addition, there are deaths that occur as a
      result of the torture. However, the Egyptian government does not give clear
      answers about the issue. Everyone could be exposed to torture, and for different,
      illogical reasons. The case of Bany Mazar is a horribly clarifying one. The
      unclear political situation and the absence of democracy play the main role in
      the highly increasing rate of torture in Egypt.

PMID- 17456906
TI  - Methods and sequelae of torture: a study in Sri Lanka.
AB  - A retrospective study was performed to document the physical and psychological
      methods of torture and their sequelae on 90 victims of torture who attended the
      Family Rehabilitation Centres in Vavuniya, Trincomalee and Anuradhapura, using a
      standard assessment format. The study showed that the methods of torture
      practised in Sri Lanka are similar to that of other countries. The methods are
      physical and psychological. Being a victim of a traumatic event would be
      physically and psychologically stressful.

PMID- 17456907
TI  - Consequences among protest survivors of 2006 in Nepal.
AB  - This study is based on the secondary data gathered from various health
      institutions, human right organizations, a political party and news agencies in
      Nepal. The Centre for Victims of Torture (CVICT) has its own primary data of
      traumatized victims from the mobile medical rescue team and from observing for
      human rights violations. There have been gross human rights abuses. Even the
      rescue team was not found to be safe from the incident. Moreover, the head and
      neck along with the vital organs of the body were made the target. The injured
      people were managed in different hospitals. Many victims suffer from the
      aftermath of this brutality through combat fatigue, also called acute crisis
      reaction. They are in need of comprehensive rehabilitation in the form of
      medical, psychological and social assistance.

PMID- 17456908
TI  - Comment on "Psychology and U.S. psychologists in torture and war in the Middle
      East".

PMID- 17456909
TI  - Immunoprophylaxis of leprosy: current status and future prospects.

PMID- 17456910
TI  - Photoprotection.
AB  - The deleterious effect of ultraviolet radiation on humans has increased the need
      for photoprotection. Sunscreens are widely used as photo protective agents. They
      are divided into chemical sunscreens which absorb high-energy ultraviolet rays
      and physical blockers which reflect or scatter light. Effectiveness of sunscreens
      depends upon sun protection factor and its substantivity. Clothing is also
      important for sun protection and its effectiveness is measured by Ultraviolet
      Protection Factor. There are many other agents with photo protective properties,
      which range from antioxidants to plant extracts to DNA repair enzymes. Usage of
      wide brimmed hats and sunglasses, avoidance of solar exposure at times of peak
      intensity, use of cover-up garments and sunscreen lotions are effective for photo
      protection of the skin.

PMID- 17456911
TI  - Physical sunscreens: on the comeback trail.
AB  - Awareness of ultraviolet radiation-induced skin damage creates the need for the
      development of broad-spectrum, safe and cosmetically acceptable sunscreens. Being
      relatively inert, safe, stable and non-irritating, physical sunscreens are
      particularly useful for patients with sensitive skin who cannot tolerate chemical
      sunscreens. However, they form a thick visible pigment layer on the skin. To
      overcome this drawback, microfine oxides have been developed which made the
      sunscreens virtually transparent when applied on the skin. This article reviews
      the rationale for the comeback of physical sunscreens by analyzing data from
      various sources.

PMID- 17456912
TI  - Protective effect of bacillus Calmette Guerin (BCG) vaccine in the prevention of
      leprosy: a meta-analysis.
AB  - BACKGROUND: Although the role of bacillus Calmette Guerin (BCG) vaccine in the
      prevention of leprosy was hypothesized as early as 1939, its level of protective
      effect remained controversial. AIM: As a meta-analysis systematically combines
      the results from different studies, we summarize the protective effect of BCG
      vaccine in prevention of leprosy using meta-analytic procedures. METHODS: Our
      search strategy included a computerized literature search, snowballing technique
      to identify potential studies, review of previously compiled lists of BCG studies
      and articles, contacting experts on BCG vaccination and manual search to locate
      articles in non-indexed journals. The present meta-analysis included 22 studies
      (6 trials, 2 cohort studies and 14 case-control studies) on the role of BCG
      vaccine in the prevention of leprosy. The random effects model as described by
      DerSimonian and Laird was used to summarize the effect measures. For each
      summarization, a Chi-square test of heterogeneity was estimated. To strengthen
      the viewpoint further additional information from the studies which were not
      included in meta-analysis, was also utilized. RESULTS: The summary protective
      effects calculated from trials, cohort studies and case-control studies were 43
      (27-55), 62 (53-69) and 58 (47-67)% respectively, which were statistically
      significant. These estimates confirmed the protective association between BCG
      vaccination and leprosy. Review of 29 studies focusing on the role of BCG
      vaccination in the prevention of leprosy revealed that not a single study
      reported a negative protective effect. Thirteen (44.8%) studies demonstrated
      greater than or equal to 50% efficacy/effectiveness. CONCLUSION: There is
      sufficient and convincing evidence of the protective effect of BCG vaccine
      against leprosy, as reflected from the meta-analysis and overall review of 29
      studies of BCG vaccination and leprosy.

PMID- 17456913
TI  - Efficacy of topical azelaic acid gel in the treatment of mild-moderate acne
      vulgaris.
AB  - BACKGROUND: Twenty percent azelaic acid gel is recommended as a topical treatment
      for acne due to its favorable profile. AIM: Our objective in this study was to
      evaluate the efficacy of 20% azelaic acid gel in the treatment of mild to
      moderate acne vulgaris. METHODS: This was a double blind, randomized clinical
      trial. Sixty patients with mild to moderate acne vulgaris were selected randomly
      to receive either azelaic acid gel or the vehicle gel alone. Patients were
      followed up every 15 days for a period of 45 days. The number of lesions and the
      acne severity index (ASI) were recorded and compared using Student's t-test.
      RESULTS: Total lesion count was reduced by 60.6% and 19.9% by azelaic acid gel
      and the placebo respectively (P = 0.002). ASI was reduced by 65.2% and 21.3% by
      azelaic acid gel and the placebo respectively (P = 0.001), i.e, azelaic acid gel
      was 3.06 times more effective than the placebo in reducing ASI. CONCLUSION:
      Azelaic acid gel can be used as an effective treatment in mild to moderate acne
      vulgaris.

PMID- 17456914
TI  - Determination of minimal erythemal dose for narrow band-ultraviolet B radiation
      in north Indian patients: comparison of visual and Dermaspectrometer readings.
AB  - BACKGROUND: Minimal erythemal dose (MED) for narrow band-ultraviolet B radiation
      (NB-UVB) varies with race and skin type. The aim was to estimate the MED for NB
      UVB and compare visual readings with those from a Dermaspectrometer in a north
      Indian patients as the available data is sparse. METHODS: Forty one patients who
      visited the dermatology outpatient department were recruited for this study. Skin
      type was grouped as per Fitzpatrick skin type scale. Patients' upper backs were
      irradiated after applying a novel template with 8 windows of 2 x 2 cm each, with
      a test dose ladder of 250-1500 mJ/cm2 in a Waldmann (700K) TL-01 chamber. MED and
      erythema index were read after 24 hours, the latter by using Dermaspectrometer.
      RESULTS: Forty one patients (10 males, 31 females) with mean age of 30.5 (14-65)
      years were recruited. 23 patients were of skin type 5, 17 of type 4 and one of
      skin type 3. The estimated MEDs were 1000 mJ/cm2 in 17, 750 mJ/cm2 in 19, 1100
      mJ/cm2 in four and 500 mJ/cm2 in one patient. The median and mode MED was 1000
      mJ/cm2. There was an exponential rise in the erythema index with increase in
      irradiation (17.18-26.25/250-1500 mJ/cm2). Student's t-test applied to detect
      differences between the visual and Dermaspectrometer readings was found to be
      statistically not significant. CONCLUSION: The estimated MED for NB-UVB varied
      from 500 to 1100 mJ/cm2, the median MED being 1000 mJ/cm2. The darker skin types
      did not have low MED while some patients with lighter skin type displayed lower
      MED. There was no significant difference in MED determined by visual and
      Dermaspectrometer readings.

PMID- 17456915
TI  - A clinical and histopathological study of pityriasis lichenoides.
AB  - BACKGROUND: Pityriasis lichenoides is a papulosquamous disorder of unknown
      etiology with remissions and exacerbations. Histopathology helps greatly in the
      diagnosis of this condition. AIM: We studied clinical and histopathological
      features of pityriasis lichenoides in our patients. METHODS: This is a 3-year
      retrospective and prospective, descriptive study of all patients clinically
      diagnosed as pityriasis lichenoides and confirmed by histopathology. All patients
      were studied clinically and histopathologically. RESULTS: There were 51 (30 males
      and 21 females) cases of pityriasis lichenoides in the study period. The maximum
      number of cases, 14 (27.45%) were in their second decade of life. Pityriasis
      lichenoides chronica was diagnosed in 39 cases (76.47%) and pityriasis
      lichenoides et varioliformis acuta (PLEVA) in 12 cases (23.53%).
      Histopathologically, basal cell vacuolation and perivascular infiltrate were seen
      in all the cases. Exocytosis was seen in 45.1% of the cases. All the cases of
      PLEVA showed lymphocytic vasculitis albeit without fibrinoid deposition in the
      vessel walls. CONCLUSION: Pityriasis lichenoides is not a rare disorder, and is
      not a true lymphocytic vasculitis as blood vessel damage and fibrinoid deposition
      in the blood vessel walls were not seen in this study.

PMID- 17456916
TI  - Type I hypersensitivity to Parthenium hysterophorus in patients with parthenium
      dermatitis.
AB  - BACKGROUND: Parthenium dermatitis is a major problem in urban and rural India.
      Patients with severe allergic rhinitis due to exposure to pollens of parthenium
      are reported to have parthenium specific IgE and IgG antibodies. Parthenium
      induces contact dermatitis by Type IV hypersensitivity and allergic rhinitis by
      Type-I hypersensitivity. AIMS: The study was undertaken to detect Type-I and Type
      IV hypersensitivity amongst patients with parthenium dermatitis. METHODS:
      Fourteen patients with clinical features of parthenium dermatitis who patch
      tested positive to parthenium were included in the study. Patch testing was done
      by standard method and results interpreted as recommended by the ICDRG. Serum IgE
      was determined by chemiluminescence immuno assay system (CLIA). Prick testing was
      performed and interpreted by standard method. RESULTS: Twelve out of the 14
      patients included, showed a positive prick test. Serum IgE was elevated in all
      patients to varying degrees (mean IgE-1279.9 IU/ml; N--up to 100 IU/ml).
      CONCLUSION: The positive patch test, prick test and elevated serum IgE suggest
      that both Type-I and Type-IV hypersensitivity may play a role in the induction
      and perpetuation of parthenium dermatitis in most patients. To date, delayed
      hypersensitivity was thought to be solely responsible for parthenium dermatitis.
      This study suggests that a combined type-I and type IV hypersensitivity
      mechanisms may be operational.

PMID- 17456917
TI  - Cutaneous manifestations in renal failure patients: a case series.
AB  - Cutaneous involvement in renal disease is due to a host of factors ranging from
      metabolic disturbances to immunosuppressive drugs. Herein we report a series of
      six cases of renal failure with varied cutaneous manifestations ranging from
      infections to neoplasms due to prolonged immunosuppression. Our first case had
      cutaneous cryptococcosis where skin lesions gave a clue to the diagnosis of
      altered sensorium and underlying meningitis. The second case initially presented
      with florid warts and was treated successfully but later presented with an
      explosive recurrence of skin lesions due to malignant transformation. Our third
      case had basal cell carcinoma over the presternal region that was successfully
      treated with liquid nitrogen cryotherapy. Our fourth case had diabetic
      nephropathy that presented with septicemia and purpura fulminans. The last case
      had cutaneous manifestations of drug therapy because of heparin infusion. To
      conclude, cutaneous manifestations in patients with renal failure are varied and
      a high degree of suspicion is needed for early diagnosis and aggressive treatment
      to effectively combat mortality and morbidity.

PMID- 17456918
TI  - Aleukemic leukemia cutis.
AB  - Aleukemic leukemia cutis has always been a dermatological curiosity. It is a rare
      condition characterized by the infiltration of skin by leukemic cells before
      their appearance in the peripheral blood or bone marrow. A 20 year old man had
      presented with nodular swelling on the scalp of 6 months duration along with
      cervical lymphadenopathy. Biopsy and immunohistochemistry revealed myeloid
      sarcoma. The initial presentation was aleukemic and repeated peripheral blood
      counts and marrow examinations were normal. However, the outcome was fatal within
      3 months of diagnosis of cutaneous lesions.

PMID- 17456919
TI  - Pentazocine-induced leg ulcers and fibrous papules.
AB  - We herein describe a case of 55-year-old farmer, who presented with chronic non
      healing ulcers over both shins of 4 years duration. Intravenous drug abuse was
      suspected due to inability to find any venous access and all peripheral veins
      being found thickened and fibrosed. There were multiple atrophic scars in linear
      distribution in all limbs as well as in both groins. In addition there were
      multiple discrete fibrous papules in linear distribution on both hands, which
      were more obvious on the left side. The patient denied abusing intravenous drugs.
      However, his relatives confirmed that he abused pentazocine for almost one year
      before his chronic pain in abdomen was treated by appendicectomy. With subsequent
      counseling, it was found that he continued to abuse pentazocine at times even
      after surgery leading to the non-healing of ulcers.

PMID- 17456920
TI  - Langerhans cell histiocytosis of the mandible in a six-year-old child.
AB  - Histiocytosis is a term applied to a group of rare disorders of the
      reticuloendothelial system. Eosinophilic granuloma, the most benign and localized
      of the three Langerhans cell histiocytosis entities, may be solitary or multiple.
      Eosinophilic granuloma can affect almost any bone, but commonly involves the
      mandible when the jaws are affected. Conventional treatment of LCH is with
      surgery, radiotherapy, chemotherapy and steroid injections, alone or in
      combination. Spontaneous regression of localized disease has also been reported.
      We report a six and a half-year-old patient with Langerhans cell histiocytosis-
      solitary eosinophilic granuloma of the mandible that initially regressed but
      rapidly recurred even after radical treatment and had a fatal outcome.

PMID- 17456921
TI  - Blastomycosis-like pyoderma.
AB  - A 9-year-old female, presented with recurrent bilaterally symmetrically
      distributed flesh colored vegetative plaques, papules and nodules on trunk and
      upper and lower extremities since 15 days. Investigations revealed anemia,
      hypoproteinemia, decreased albumin and positive D-xylose test. Pus swab and
      biopsy for culture sensitivity showed Enterococci species. Biopsy showed
      spongiotic psoriasiform dermatitis with subcorneal pustule. She fulfilled
      criteria for the diagnosis of blastomycosis-like pyoderma viz. presentation of
      large verrucous plaques with pustules and elevated border, pseudoepitheliomatous
      hyperplasia with abscess histologically and growth of one pathogenic bacterium on
      culture or tissue biopsy. She responded to long-term amoxicillin-clavulanic acid
      therapy.

PMID- 17456922
TI  - Epidermal nuclear staining: a distinct reaction pattern in connective tissue
      diseases.

PMID- 17456923
TI  - Prolonged remission of pemphigus induced by dexamethasone-cyclophosphamide pulse
      therapy.

PMID- 17456924
TI  - Gianotti Crosti syndrome associated with transfusion acquired hepatitis B virus
      infection in a patient of sickle cell anemia.

PMID- 17456925
TI  - Localization of varicella around cutaneous leishmaniasis.

PMID- 17456926
TI  - Effect of tazarotene on ichthyosiform erythroderma of Tay's syndrome.

PMID- 17456927
TI  - Basal cell carcinoma developing in verrucous epidermal nevus.

PMID- 17456928
TI  - Methods of specimen collection for the diagnosis of STIs.

PMID- 17456929
TI  - Use of fumaric acid esters in psoriasis.
AB  - Fumaric acid esters (FAE) are chemical compounds derived from the unsaturated
      dicarbonic acid fumaric acid. The usage of FAEs in treatment of psoriasis was
      introduced in the late 1950's. In the 1980s more standardized oral preparations
      of FAEs were developed containing dimethylfumarate (DMF) and salts of
      monoethylfumarate (MEF) as main compounds. In 1994, Fumaderm an enteric-coated
      tablet containing DMF and calcium, magnesium and zinc salts of MEF was approved
      for the treatment of psoriasis in Germany and since then has become the most
      commonly used systemic therapy in this country. Fumaric acids have been proven to
      be an effective therapy in patients with psoriasis even though the mechanisms of
      action are not completely understood. About 50-70% of the patients achieve PASI
      75 improvement within four months of treatment and without any long-term
      toxicity, immunosuppressive effects or increased risk of infection or malignancy.
      Tolerance is limited by gastrointestinal side effects and flushing of the skin.
      This article reviews pharmacokinetics, uses, contraindications, dosages and side
      effects of treatment with FAEs.

PMID- 17456930
TI  - www.derm101.com: a growing online resource for learning dermatology and
      dermatopathology.
AB  - The internet is increasingly being used to distribute knowledge in medicine in
      novel and unconventional ways. In this article, we give a brief introduction into
      the website www.derm101.com, which was founded by A. B. Ackerman for the purpose
      of teaching dermatology and dermatopathology. A clinical atlas, online books such
      as the 3rd edition of his volume "Histologic diagnosis of inflammatory skin
      diseases", works on clues and differential diagnoses in dermatopathology, a
      resource on therapeutic strategies in dermatology, a video lecture library on
      controversial issues in dermatology, the quarterly online journal
      Dermatopathology: Practical and Conceptual and much more can be found on
      derm101.com. The site is enriched with new contents biweekly and offers several
      interactive teaching devices. Currently, www.derm101.com is the most
      comprehensive online library of dermatology resources.

PMID- 17456931
TI  - A large asymptomatic lesion on buttock since birth.

PMID- 17456932
TI  - Institutional review boards and new patient privacy issues in publication.

PMID- 17456933
TI  - Global variation and pattern changes in epidemiology of uveitis.
AB  - Uveitis, a complex intraocular inflammatory disease results from several
      etiological entities. Causes of uveitis are known to vary in different
      populations depending upon the ecological, racial and socioeconomic variations of
      the population studied. Tropical countries are unique in their climate,
      prevailing pathogens and in the existing diseases, which further influence the
      epidemiological and geographical distribution of specific entities. We provide an
      overview of the pattern of uveitis of 15221 cases in 24 case series reported from
      several countries over 35 years (1972-2007) and we integrate it with our
      experience of an additional 8759 cases seen over six years (1996-2001) at a large
      community-based eye hospital. Uveitis accounted for 0.8% of our hospital-based
      outpatient visits. The uveitis was idiopathic in 44.6%, the most commonly
      identified entities in the cohort included leptospiral uveitis (9.7%),
      tuberculous uveitis (5.6%) and herpetic uveitis (4.9%). The most common uveitis
      in children below 16 years (616 patients; 7.0% of the total cohort) was pediatric
      parasitic anterior uveitis, (182 children, 29.5% of the pediatric cohort),
      whereas the most common uveitis in patients above 60 years (642 patients; 7.3% of
      the total cohort) was herpetic anterior uveitis, (78 patients, 12.1% of the
      elderly cohort). Etiologies varied with the age group of the patients. As in
      other tropical countries, a high prevalence of infectious uveitis was seen in
      this population.

PMID- 17456934
TI  - Primary intraocular lens implantation in the first two years of life: safety
      profile and visual results.
AB  - PURPOSE: To study the safety profile of primary intraocular lens (IOL)
      implantation in the first two years of life. MATERIALS AND METHODS: A prospective
      nonrandomized, interventional study was done at the tertiary care center. Forty
      five eyes of 27 children (aged three weeks to two years) with congenital cataract
      who underwent phacoaspiration with continuous curvilinear capsulorrhexis combined
      with primary posterior capsulotomy and anterior vitrectomy with in the bag
      placement of IOL at primary surgery were included. Outcome measures were clarity
      of visual axis, postoperative inflammation, fixation pattern and retinoscopy.
      RESULTS: The mean IOL power was 23.95 +/- 0.87 diopter (D) (range 22D to 27D).
      Follow-up ranged from 12 months to 48 months (mean 18 +/- 9.13 months). In
      infants, hypermetropia decreased from 6.60D +/- 2.64D at one week postoperatively
      to 3.03D +/- 2.53D at one year following surgery and 4.78D +/- 1.93D to 2.56D +/-
      1.5D in children older than one year at the time of surgery. Re-opacification of
      the central visual axis was observed in six eyes (13.3%). Significant posterior
      synechiae due to irido-capsular adhesion was seen in seven eyes (15.6%). Five of
      these seven eyes also had significant posterior capsular opacification.
      CONCLUSIONS: Meticulously performed primary IOL implantation and primary
      posterior capsulorrhexis with anterior vitrectomy in the first two years of life
      is a safe and effective method of aphakic correction.

PMID- 17456935
TI  - Evaluation of retinal nerve fiber layer thickness measurement following laser in
      situ keratomileusis using scanning laser polarimetry.
AB  - AIM: To evaluate the effect of laser-assisted in situ keratomileusis (LASIK) on
      the measurement of retinal nerve fiber layer thickness by scanning laser
      polarimetry using customized corneal compensation in myopes. MATERIALS AND
      METHODS: Scanning laser polarimetry was performed on 54 eyes of 54 healthy
      patients with myopia using the glaucoma diagnostics variable corneal compensation
      (GDx VCC) instrument (Laser Diagnostic Technologies, San Diego, California)
      before and a week after LASIK. The various parameters were compared using the
      Student's t test. RESULTS: No statistically significant change was observed in
      any of the retinal nerve fiber layer parameters before and after LASIK.
      CONCLUSIONS: While the measurement of retinal nerve fiber layer thickness by
      scanning laser polarimetry is affected by anterior segment birefringent
      properties and LASIK would be expected to produce changes in the same, customized
      corneal compensation using the GDx VCC seems to adequately compensate for these
      changes.

PMID- 17456936
TI  - Lipoprotein(a) as a risk factor for diabetic retinopathy in patients with type 2
      diabetes mellitus.
AB  - AIMS: To estimate serum lipoprotein(a) [Lp(a)] levels in patients with type 2
      diabetes mellitus with and without diabetic retinopathy and to determine the
      correlation, if any, between serum Lp(a) levels and severity of diabetic
      retinopathy. MATERIALS AND METHODS: The study included a total of 200 patients of
      type 2 diabetes mellitus out of which 100 patients who had no retinopathy served
      as the control group and 100 patients with diabetic retinopathy formed the study
      group. A detailed fundus examination was done with dilated pupil. The Lp(a)
      levels were measured quantitatively in fasting venous samples by an
      immunoturbidimetric method using commercially available kits (Clonital).
      STATISTICAL ANALYSIS USED: Group comparisons involving qualitative measures were
      carried out using Chi square test. ANOVA procedure was applied for comparing
      group means. Logistic regression analysis was performed for independent factors
      associated with diabetic retinopathy. RESULTS: The average Lp(a) levels in the
      study group (68.5 mg/dl) were significantly higher than in the control group
      (25.1 mg/dl) (P 0.001). The Lp(a) levels were found to increase with increasing
      severity of diabetic retinopathy. CONCLUSIONS: Serum Lp(a) levels are
      significantly raised in patients with diabetic retinopathy as compared to those
      with no retinopathy.

PMID- 17456937
TI  - Analysis of juvenile idiopathic arthritis associated uveitis in India over the
      last 16 years.
AB  - AIM: Juvenile idiopathic arthritis (JIA) associated uveitis is one of the most
      common causes of visual morbidity in children. We report the systemic, clinical
      and investigational features of a cohort of all cases of JIA associated uveitis
      seen at our referral uveitis clinic between 1988 and 2004. STUDY DESIGN:
      Retrospective case series MATERIALS AND METHODS: All patients of JIA seen at the
      uveitis clinic of tertiary eye care hospital, between 1988 and 2004 with minimum
      follow up of 3 months were included. Complete history and ophthalmic evaluation
      and findings on each visit were noted. Ocular complications were identified and
      recorded. Results of laboratory investigations and diagnostic as well as
      therapeutic procedures were analyzed. A rheumatologist managed systemic status.
      RESULTS: There were 40 patients (64 eyes) with JIA. Thirty four patients (85%)
      had pauciarticular type and 6 patients (15%) had polyarticular type of JIA.
      Complicated cataract and band shaped keratopathy were seen in 38 eyes (63%) and
      37 eyes (62%) respectively. Twenty-two patients (17 bilateral and 5 unilateral)
      were treated with immunosuppressives and in 19 of these patients, the disease
      went into remission. Twenty-three eyes (38%) had improvement in visual acuity
      while in 27 eyes (45%), the vision remained stable and in 10 eyes (17%), vision
      deteriorated despite therapy. CONCLUSION: In India, JIA associated uveitis
      commonly presented in pauciarticular type with preponderance in males. Rheumatoid
      arthritis factor and anti nuclear antibodies were not as common as compared to
      the western population. Among long-term treatment options, immunosuppressives are
      a better choice. Ocular surgery was performed when mandatory for visual
      rehabilitation.

PMID- 17456938
TI  - Phacoemulsification and pars plana vitrectomy: a combined procedure.
AB  - AIM: To describe the results of a combined procedure including
      phacoemulsification, insertion of posterior chamber intraocular lens (PCIOL) and
      pars plana vitrectomy (PPV) in eyes with vitreoretinal pathology and coexisting
      significant cataract. DESIGN: Retrospective, consecutive, noncomparative,
      interventional case series. MATERIALS AND METHODS: Medical records of patients
      who had undergone phacoemulsification, PPV and PCIOL implantation as a combined
      procedure between January 2000 and December 2004 were retrospectively reviewed.
      The main outcome measures were the anatomical success of retina, defined as
      reattached retina, intraoperative and postoperative complications and functional
      success in terms of final best corrected visual acuity. RESULTS: In all, 65 eyes
      of 64 patients were included. The mean age of the patients was 50.9 years +/-
      17.1 (range, five to 82 years). Vitreous hemorrhage with or without retinal
      detachment (19 eyes, 29.2%) was the most common indication for the vitreoretinal
      procedure. Primary anatomical success of retina was achieved in 59 eyes (90.7%).
      Visual acuity improved in 48 eyes (73.8%), was unchanged in 12 eyes (18.5%) and
      deteriorated in five eyes (7.7%). Postoperative inflammation was significantly
      more in the subgroup of previously vitrectomized eyes (42%) (P =0.014, Fisher
      exact test) compared to those which underwent primary vitrectomy. CONCLUSIONS:
      Combined surgery is a feasible option for patients with vitreoretinal diseases
      and cataract.

PMID- 17456939
TI  - Visual acuity and contrast sensitivity outcomes in Indian eyes undergoing
      photodynamic therapy with intravitreal injection of triamcinolone acetonide in
      age-related macular degeneration.
AB  - PURPOSE: To evaluate photodynamic therapy (PDT) with verteporfin along with
      intravitreal triamcinolone acetonide (IVTA) in the treatment of neovascular age
      related macular degeneration (AMD). MATERIALS AND METHODS: This prospective
      interventional case series included 23 patients (23 eyes) of choroidal
      neovascularization due to neovascular AMD who were treated with PDT with
      verteporfin followed by an injection of 4 mg IVTA. The main outcome measures were
      visual acuity (VA), contrast sensitivity, retreatment frequency with PDT (and
      triamcinolone) and frequency of side-effects. RESULTS: Twenty-three eyes
      underwent PDT with verteporfin followed by IVTA one week later. All patients were
      followed up for one year. Initial VA ranged from 20/32 to 20/800 and final VA
      ranged from 20/40 to 20/500 at the end of 12 months. VA stabilized (that is
      loss/gain < 2 lines) in 19 (82%) eyes. Contrast sensitivity also improved in
      16/23 eyes (70%). Lesion type and patient's age had no influence on the outcome,
      but baseline VA had a borderline statistically significant effect (P =0.059). Six
      eyes (27%) had an increase in intraocular pressure that required therapy. There
      were no cases of endophthalmitis, but four eyes (18%) developed significant
      cataract that required surgery during the follow-up period. CONCLUSION: The
      combination of PDT along with IVTA improves contrast sensitivity and stabilizes
      vision during one-year follow-up.

PMID- 17456940
TI  - Can the Bruckner test be used as a rapid screening test to detect significant
      refractive errors in children?
AB  - PURPOSE: To assess the suitability of Bruckner test as a screening test to detect
      significant refractive errors in children. MATERIALS AND METHODS: A pediatric
      ophthalmologist prospectively observed the size and location of pupillary
      crescent on Bruckner test as hyperopic, myopic or astigmatic. This was compared
      with the cycloplegic refraction. Detailed ophthalmic examination was done for
      all. Sensitivity, specificity, positive predictive value and negative predictive
      value of Bruckner test were determined for the defined cutoff levels of
      ametropia. RESULTS: Ninety-six subjects were examined. Mean age was 8.6 years
      (range 1 to 16 years). Bruckner test could be completed for all; the time taken
      to complete this test was 10 seconds per subject. The ophthalmologist identified
      131 eyes as ametropic, 61 as emmetropic. The Bruckner test had sensitivity 91%,
      specificity 72.8%, positive predictive value 85.5% and negative predictive value
      83.6%. Of 10 false negatives four had compound hypermetropic astigmatism and
      three had myopia. CONCLUSIONS: Bruckner test can be used to rapidly screen the
      children for significant refractive errors. The potential benefits from such use
      may be maximized if programs use the test with lower crescent measurement
      cutoffs, a crescent measurement ruler and a distance fixation target.

PMID- 17456941
TI  - Role of fine needle aspiration cytology in diagnosis of eyelid sebaceous
      carcinoma.
AB  - Sebaceous carcinoma of the ocular adnexa is a malignant neoplasm which can
      exhibit aggressive local behavior and can metastasize to regional lymph nodes and
      distant organs. The neoplasm is known to masquerade as other benign and less
      malignant lesions, resulting in delay in diagnosis and relative high morbidity
      and mortality. Fine needle aspiration cytology (FNAC) of recurrent upper eyelid
      nodules treated elsewhere as chalazion was done. Cytological smears were
      suggestive of malignancy. Subsequently histopathology confirmed the diagnosis of
      sebaceous gland carcinoma. Eyelid reconstruction was done after
      histopathologically confirmed tumor-free margins. The article highlights the role
      of FNAC in early diagnosis and subsequent appropriate surgical management of
      eyelid sebaceous gland carcinoma to prevent recurrence and metastasis.

PMID- 17456942
TI  - Craniodiaphyseal dysplasia: an unusual cause of recurrent dacryocystitis.
AB  - We describe a rare syndrome characterized by severe craniofacial hyperostosis,
      sclerosis, obliteration of paranasal sinuses and foramina of skull base, in a 10
      year-old female child who presented with abnormal facial features and recurrent
      dacryocystitis due to narrowing of nasolacrimal duct.

PMID- 17456943
TI  - Double combined pigment epithelial and retinal hamartomas in a single eye: an
      optical coherence tomographic study.
AB  - Combined retinal pigment epithelial and retinal hamartomas are focal
      malformations composed of overgrowth of mature glial, vascular and pigmented
      cells. They are usually solitary and unilateral. In addition there are only a few
      optical coherence tomographic reports of the same. We report a rare case of twin
      hamartomas in the same eye and their unique optical coherence tomographic
      findings that are different from previous reports.

PMID- 17456944
TI  - Unilateral hypopyon in a child as a first and sole presentation in relapsing
      acute lymphoblastic leukemia.
AB  - Ocular manifestations form a part of the spectrum of varied clinical
      presentations in leukemias. Most of the ophthalmic manifestations are related to
      central nervous system leukemia and bone marrow relapse. We report a case of
      acute unilateral hypopyon uveitis as an initial presenting feature of relapsing
      acute lymphoblastic leukemia (ALL) in a pediatric patient. Anterior chamber
      paracentesis was performed in a four-year-old male child presenting with
      unilateral treatment-resistant hypopyon after remission of ALL. Examination of
      aqueous humor aspirate revealed presence of malignant cells. Atypical hypopyon,
      even unilateral can be an indication of relapsing ALL in a child.

PMID- 17456945
TI  - Serous macular detachment associated with dysplastic disc.
AB  - The article describes a case of abnormal looking optic disc (dysplastic)
      associated with serous macular detachment similar to what is described in cases
      of optic pit. However clinically as well as on fluorescein angiography, no optic
      pit or coloboma could be identified. Gas injection, prone positioning and laser
      along the temporal border of the disc could correct the macular detachment.

PMID- 17456946
TI  - Anterior chamber exudative mass due to Scedosporium apiospermum in an
      immunocompetent individual.
AB  - Endogenous intraocular infection of fungal etiology is extremely rare in an
      immunocompetent individual. Usually, an antecedent history of trauma, surgery,
      intravenous drug abuse or an immunocompromized state can be elicited.
      Scedosporium apiospermum is a known cause of keratomycosis after traumatic
      implantation and can cause fatal disseminated infection in immunocompromized
      patients. However, cases of S. apiospermum intraocular infection in
      immunocompetent individuals have been very rarely reported in literature. We
      report here a case of an anterior chamber exudative mass due to S. apiospermum in
      an immunocompetent individual which was managed successfully with anterior
      chamber wash and intravitreal injection of voriconazole.

PMID- 17456947
TI  - Herniation of the anterior lens capsule.
AB  - Herniation of the anterior lens capsule is a rare abnormality in which the
      capsule bulges forward in the pupillary area. This herniation can be mistaken for
      an anterior lenticonus where both the capsule and the cortex bulge forward. The
      exact pathology behind this finding is still unclear. We report the clinical,
      ultrasound biomicroscopy (UBM) and histopathological findings of a case of
      herniation of the anterior lens capsule. UBM helped to differentiate this entity
      from anterior lenticonus. Light microscopy revealed capsular splitting suggestive
      of capsular delamination and collection of fluid (aqueous) in the area of
      herniation giving it a characteristic appearance.

PMID- 17456948
TI  - Endogenous endophthalmitis in a rheumatoid patient on tumor necrosis factor alpha
      blocker.
AB  - The development of anti-tumor necrosis factor (TNF) therapies is a milestone in
      the therapy of rheumatic diseases. It is of concern whether all potential
      undesired complications of therapy have been evaluated within clinical trials
      which have led to treatment approval. Specialists prescribing TNF blockers should
      be aware of the unusual and severe complications that can occur. We describe a
      case of endogenous endophthalmitis in a rheumatoid patient on TNF alpha blocker.

PMID- 17456949
TI  - Traumatic expulsive aniridia after phacoemulsification.
AB  - Blunt trauma is usually associated with severe ocular damage particularly in eyes
      following cataract surgery. Small, self-sealing incision cataract surgery is
      changing the pattern of presentation of such cases, with relatively favorable
      outcomes. We describe a case of blunt trauma following phacoemulsification
      leading to aniridia.

PMID- 17456950
TI  - Optical coherence tomography following successful management of endophthalmitis.
AB  - Optical coherence tomography (OCT) was done in 20 eyes to detect causes of poor
      visual outcome, at least three months after successful management of
      endophthalmitis, which obtained clear media and best corrected visual acuity of <
      20/40. Only four (20%) eyes had normal foveal contour on OCT. Eleven (55%) eyes
      showed treatable lesions, including epiretinal membrane with macular thickening
      in five (25%), epiretinal membrane without macular thickening in three (15%),
      cystoid macular edema in two (10%) and subfoveal serous detachment in one (5%)
      eye. Five eyes (25%) had foveal atrophy. OCT was helpful in segregating treatable
      conditions like cystoid macular edema from nontreatable causes like neurosensory
      atrophy in the postendophthalmitis patients.

PMID- 17456951
TI  - Parinaud's syndrome in a patient with thalamic infarction due to cerebral venous
      thrombosis.

PMID- 17456952
TI  - "Reverse" optic capture complicating retained viscoelastic in capsular bag
      following phacoemulsification.

PMID- 17456953
TI  - Panophthalmitis due to Aspergillus in an acquired immunodeficiency syndrome
      patient: clinicopathological study of a case.

PMID- 17456954
TI  - Ultrastructural study of a contusion cataract.

PMID- 17456955
TI  - Heavy eye phenomenon in association with zonular cataracts.

PMID- 17456956
TI  - Subconjunctival larva migrans caused by sparganum.

PMID- 17456957
TI  - Guest editorial.

PMID- 17456959
TI  - The dental and oral status of children with chronic renal failure.
AB  - The main purpose of this investigation was to evaluate the oral and dental status
      of chronic renal failure (CRF) patients undergoing hemodialysis at children's
      Hospitals in Tehran. Fifty-three children with CRF aged 5-18 years recruited from
      the renal unit of children's medical center, Tehran Hospitals for children, were
      studied. The decayed, missing, filled dmf, DMF and MGI scores were recorded. The
      CRF children had low prevalence of dental caries, although none of the clinical
      diagnoses displayed the absence of gingival inflammation. Duration of dialysis
      and Anemia had a significant influence on the gingival condition. Especially
      anemia leads to severe gingivitis. The CRF children need careful monitoring and
      all such patient should be given oral hygiene education as topmost priority.

PMID- 17456960
TI  - The use of index of orthodontic treatment need in an Iranian population.
AB  - This study aims to evaluate the need for orthodontic treatment between 11 and 14
      year old school children in Shiraz. A sample of 2000 students consisting of 1200
      boys and 800 girls from various parts of the city was selected. The index of
      orthodontic treatment need (IOTN) was used by two calibrated examiners. The data
      was recorded in questionnaires to assess dental health components (DHC).
      Aesthetic components (AC) were evaluated both by students (AC) and examiners
      (ACE). The results for DHC of IOTN were: 18.39% of population showed severe and
      very severe need for treatment, 25.8% were in border line category, 48.1% had a
      slight need and the percentage for no need to treatment was 7.63%. In evaluating
      AC, 91.93% were in no need or little need, 3.91% in moderate need and 4.11% in
      great need to treatment group. Where as ACE resulted in: 91.31% no need and
      little need, 2.44% moderate need and 6.21% great need to treatment. There was a
      slight statistical correlation (0.54) between AC and ACE, but a very weak
      correlation between DHC and AC was observed. According to DHC, boys showed more
      need for treatment than girls (P=0.001). Grade 8 showed the most percentage in
      great need category in both AC and ACE (3.41% of 4.11% and 5.74% of 6.21%,
      respectively). The results indicate that the need for orthodontic treatment was
      less than other studies and most of the students were in the category of little
      need for treatment.

PMID- 17456961
TI  - Status of oral health awareness in Indian children as compared to Western
      children: a thought provoking situation (a pilot study).
AB  - A study was conducted to evaluate the level of oral health awareness in a
      selected sample of Indian children and a selected sample of western children
      residing in Amritsar city of Punjab. Children were evaluated on the basis of a
      standardized questionnaire developed by WHO, for health awareness in children.
      Final results revealed the level of awareness in both the groups and the
      practical application of their knowledge about dental health in day to day life.

PMID- 17456962
TI  - Comparison of salivary fluoride levels following use of dentifrices containing
      different concentrations of fluoride.
AB  - Many industrialized countries have reported a decline in caries prevalence over
      the past few decades. These reductions have been related to the regular use of
      fluoride dentifrices. Fluoride dentifrices are the most cost-effective and
      efficient means of caries prevention. However, there have been concerns regarding
      the risk of fluorosis in children due to the ingestion of dentifrices. This has
      led to the use of dentifrices with low concentration of fluoride. Salivary
      fluoride levels after tooth-brushing have been shown to be related to the
      anticaries efficacy of fluoride dentifrices. The present study was designed to
      evaluate the effect of the concentration of fluoride in the dentifrice, on the
      salivary fluoride level in children. Twenty children in the age group of five to
      six years were randomly selected and divided into two groups using, either 500ppm
      or 1000ppm fluoride dentifrice (sodium monofluorophosphate). Salivary fluoride
      levels at 0, 15, 30, 45, 60, minutes after brushing were estimated. The data
      collected was statistically evaluated using the unpaired t-test. The results
      showed that salivary fluoride levels following use of 500ppm fluoride dentifrice
      were significantly lower than 1000ppm fluoride dentifrice. The low salivary
      fluoride levels may thereby reduce the anticaries efficacy. Hence, the pros and
      cons of recommending a low fluoride concentration dentifrice must be judiciously
      considered.

PMID- 17456963
TI  - Spontaneous closure of midline diastema following frenectomy.
AB  - Maxillary midline diastema is a common aesthetic problem in mixed and early
      permanent dentitions. The space can occur either as a transient malocclusion or
      created by developmental, pathological or iatrogenical factors. Many innovative
      therapies varying from restorative procedures such as composite build-up to
      surgery (frenectomies) and orthodontics are available. Although literature says
      every frenectomy procedure should be preceded by orthodontic treatment, we opted
      for frenectomy technique without any orthodontic intervention. Presented herewith
      is a case report of a 9-year-old girl with a high frenal attachment that had
      caused spacing of the maxillary central incisors. A spontaneous closure of the
      midline diastema was noted within 2 months following frenectomy. The patient was
      followed up for 4 months after which the space remained closed and there was no
      necessity for an orthodontic treatment at a later stage.

PMID- 17456964
TI  - Cherubism in siblings: A case report.
AB  - Cherubism is a benign disease of bones affecting the jaws and giving a
      characteristic cherubic appearance to the patient. On radiography, the lesions
      exhibit bilateral multilocular radiolucent areas. Histopathology shows numerous
      multinucleated giant cells in the background of proliferating fibrous connective
      tissue. Cherubism can be a solitary case. The present report describe cherubism
      in two siblings and briefly review the literature on this subject.

PMID- 17456965
TI  - Facial plexiform neurofibroma in a child with neurofibromatosis type I: a case
      report.
AB  - Plexiform neurofibroma is a non-circumscribed, thick and irregular benign tumor
      of the peripheral nerve sheath. It is a virtually pathognomonic and often
      disabling feature of neurofibromatosis type I. The diffuse and soft nature of
      plexiform neurofibroma is often compared to 'a bag of worms' and is difficult to
      distinguish from a vascular malformation or a lymphangioma, thus necessitating
      thorough clinical and histopathological examination and imaging of the lesion. We
      present a case of plexiform neurofibroma in a 12-year-old male child.

PMID- 17456966
TI  - Treatment of space loss caused by submerged maxillary second primary molar.
AB  - Submersion is a clinical term describing a tooth depressed below the occlusal
      plane. In this case report, we present the treatment of a patient who had totally
      submerged primary maxillary second molar, which caused impaction of the second
      premolar and space loss in the maxillary arch due to tipping of adjacent teeth. A
      12-year-old girl was referred to the pediatric dentistry clinic. The intra-oral
      examination revealed that right maxillary second primary molar was localized
      buccal side of posterior maxillary alveolar process, being almost completely
      covered by gingiva and adjacent teeth inclined closing the space of the related
      teeth completely. Periapical radiograph demonstrated that maxillary second
      premolar was impacted. Based on clinical and radiographic findings, maxillary
      primary second molar was extracted. Headgear was used for the distalization of
      maxillary right first molar in order to create space for the impacted second
      premolar. Eruption begun spontaneously 6 months later.

PMID- 17456967
TI  - Crossed hemifacial hyperplasia: a diagnostic dilemma.
AB  - Crossed hemifacial hyperplasia is a rare condition producing facial asymmetry and
      overgrowth of the extremities of the opposite side. Very few cases are reported
      in literature. A case of an 11-year-old female is presented here to supplement
      existing clinical knowledge with many of the reported clinical and orofacial
      findings. Emphasis is placed on diagnosis of the condition by thoughtful
      elimination and the necessity of a multi-disciplinary approach to its management.

PMID- 17456968
TI  - Clinical and intraoral findings of a patient with tricho-rhino-phalangeal
      syndrome type I.
AB  - Tricho-rhino-phalangeal syndrome (TRPS) is a rare and an autosomal dominant
      disorder having the following characteristics: slowly growing sparse hair,
      medially thick and laterally thin eyebrows, bulbous tip of the nose, long flat
      philtrum and thin upper lip with vermilion border, protruding ears, cone-shaped
      epiphyses and swelling. Our report intends to introduce TRPS to the dental
      literature and to present oral, clinical and radiological data of a patient with
      TRPS. A rare association of supernumerary teeth was also diagnosed and one of
      them was extracted as it impeded on the eruption path of left premolar tooth.

PMID- 17456969
TI  - Aglossia: a case report.
AB  - A female child of 4 years with congenital absence of tongue has been described.
      This anomaly is usually associated with other congenital defects particularly
      limb and other cranio-facial defects. But in this case, the child enjoys the
      normal life, the unusual absence of tongue; she used to go to school play around
      with her friends and had a comparable I.Q.

PMID- 17456970
TI  - Reactivation of trigeminal neuralgia following distraction osteogenesis in an 8
      year-old child: report of a unique case.
AB  - Trigeminal neuralgia is extremely rare in children. No concrete treatment
      protocols seem to be available for management of this condition in the pediatric
      population. Although trigeminal neuralgia may achieve remission, the possibility
      of reactivation of a hitherto quiescent condition cannot be ruled out. We present
      a case of pediatric trigeminal neuralgia following distraction osteogenesis of
      the mandible.

PMID- 17456971
TI  - Talon's cusp: report of four unusual cases.
AB  - Talon cusp is a developmental dental anomaly thought to arise as a result of
      evagination on the surface of a tooth crown before calcification has occurred.
      The etiology remains unknown. The incidence is 0.04-10%. Any tooth may have a
      talon cusp but most of the cases involve maxillary lateral incisors, with some
      instances of bilateral involvement. The anomaly has been reported to be rare in
      the mandible. This article reports four cases of talon cusp. The first and the
      second cases describe bilateral involvement of talon cusp on palatal surfaces of
      maxillary primary centrals; in the third case talon tubercle occurs on palatal
      surfaces of both maxillary permanent lateral incisors and the maxillary left
      central incisor and in the last case a talon cusp in the lingual surface of
      mandibular permanent lateral incisor.

PMID- 17456972
TI  - Dentigerous cyst associated with multiple mesiodens: a case report.
AB  - Dentigerous cyst is a developmental odontogenic cyst, which apparently develops
      by accumulation of fluid between reduced enamel epithelium and the tooth crown of
      an unerupted tooth. When observed with erupted and complete dentition the
      diagnosis is a surprise; as about 95% of dentigerous cysts involve the permanent
      dentition and only 5% are associated with supernumerary teeth. The usual age of
      clinical presentation of dentigerous cyst due to supernumerary tooth is during
      the first four decades. Mesiodens is a supernumerary tooth situated between the
      maxillary central incisors. More frequently the mesiodens occurs unilaterally,
      but it may also be bilateral, while three or more supernumerary teeth in the
      median region of the palate are more rarely found. We report a rare case of
      dentigerous cyst in association with multiple mesiodens in a 14-year-old female
      patient.

PMID- 17456973
TI  - N'-(alpha-aminoacyl)- and N'-alpha-(N(alpha)-alkylamino)acyl derivatives of
      vancomycin and eremomycin. I. Synthesis of N'-(alpha-aminoacyl)- and N'-alpha
      (N(alpha)-alkylamino)acyl derivatives of vancomycin and eremomycin by selective
      aminoacylation of the amino sugar of the disaccharide branch.
AB  - The acylation of unprotected vancomycin or eremomycin with activated esters of
      N(alpha)-protected amino acids or N(alpha)-alkyl-N(alpha)-Fmoc-amino acids is
      directed selectively to the amino group of the disaccharide branch (N') and after
      Fmoc-group removal leads to the corresponding N'-alpha-aminoacyl derivatives. A
      series of N'-alpha-aminoacyl and N'-alpha-(N(alpha)-alkylamino)acyl derivatives
      of eremomycin and vancomycin containing hydrophobic moieties has been
      synthesized. The structures of all derivatives were confirmed by Electrospray
      Ionization mass-spectral (ESI MS) analysis, and by chemical degradation methods.
      Position of the introduced N'-alpha-aminoacyl- and N-(N(alpha)-alkylamino)acyl
      groups were determined after Edman degradation and acidic hydrolysis. The
      structures of the synthesized starting reagents (N(alpha)-alkylamino acids or
      N(alpha)-alkyl-N(alpha)-Fmocamino acids) were confirmed by NMR-spectra data. In
      general, N'-(N-alkylglycyl)-derivatives were more active than the corresponding
      N'-alpha-(N(alpha)-alkylamino)acylated derivatives containing other amino acids
      (L-Lys, L-Met, L-Orn, L- and D-Ala, L- and D-Phe and benzyl-O-L-Tyr).

PMID- 17456974
TI  - N'-(alpha-aminoacyl)- and N'-alpha-(N-alkylamino)acyl derivatives of vancomycin
      and eremomycin. II. Antibacterial activity of N'-(alpha-aminoacyl)- and N'-alpha
      (N-alkylamino)acyl derivatives of vancomycin and eremomycin.
AB  - The antibacterial activities of the series of novel N'-(alpha-aminoacyl)- and N'
      alpha-(N-akylamino)acyl derivatives of eremomycin and vancomycin containing
      hydrophobic moieties have been investigated. The N'-(N-alkylglycyl) derivatives
      of vancomycin are more active against vancomycin-susceptible staphylococci and
      enterococci and glycopeptide intermediate-resistant Staphylococcus aureus (GISA)
      than the corresponding eremomycin derivatives, but except for N'-[N-(p
      octyloxybenzyl)glycyl-vancomycin] (28) and N'-[N-(p-octyloxybenzyl)-L-alanyl
      vancomycin (33)--they are less active against glycopeptide-resistant enterococci
      (GRE). Derivatives 28 and 33 are the most active compounds (MIC's for
      glycopeptide-sensitive staphylococci and enterococci are 0.25 approximately 1
      microg/ml, for GISA 1 approximately 2 microg/ml, for GRE 2 approximately 6
      microg/ml). In in vivo studies, derivative 28 was active against S. aureus
      infections in mice with ED(50) 1 mg/kg versus 2 mg/kg for vancomycin (iv). In
      general N'-(N-alkylglycyl)-derivatives of vancomycin and eremomycin were more
      active than the corresponding N'-aminoacylated derivatives of these antibiotics
      containing other than glycin amino acids (L-Lys, L-Met, L-Orn, L- and D-Ala) and
      also L- and D-Phe or benzyl-O-L-Tyr.

PMID- 17456975
TI  - Urukthapelstatin A, a novel cytotoxic substance from marine-derived
      Mechercharimyces asporophorigenens YM11-542. I. Fermentation, isolation and
      biological activities.
AB  - Urukthapelstatin A, a novel cyclic peptide, was isolated from the cultured
      mycelia of marine-derived Thermoactinomycetaceae bacterium Mechercharimyces
      asporophorigenens YM11-542. The peptide was purified by solvent extraction,
      silica gel chromatography, ODS flash chromatography, and finally by preparative
      HPLC. Urukthapelstatin A dose-dependently inhibited the growth of human lung
      cancer A549 cells with an IC(50) value of 12 nM. Urukthapelstatin A also showed
      potent cytotoxic activity against a human cancer cell line panel.

PMID- 17456976
TI  - Urukthapelstatin A, a novel cytotoxic substance from marine-derived
      Mechercharimyces asporophorigenens YM11-542. II. Physico-chemical properties and
      structural elucidation.
AB  - The new cyclic peptide antibiotic, urukthapelstatin A, has been isolated from a
      culture of Thermoactinomycetaceae bacterium Mechercharimyces asporophorigenens
      YM11-542. The structure of urukthapelstatin A was elucidated by NMR, MS, Marfey
      analysis, chiral HPLC and X-ray crystal analyses.

PMID- 17456977
TI  - Biotransformation of cinobufagin by Cunninghamella elegans.
AB  - Cunninghamella elegans has been employed for the biotransformation of cinobufagin
      to afford 5 metabolites. The structures of the transformation products have been
      characterized as 12alpha-hydroxybufagin, 11alpha-hydroxybufagin, 12beta-hydroxy
      desacetylcinobufagin, 3-oxo-12alpha-hydroxybufagin and 12beta-hydroxybufagin.
      Products 12alpha-hydroxybufagin and 11alpha-hydroxybufagin are new compounds. In
      vitro both the biotransformation products and cinobufagin all showed cytotoxic
      activities against HeLa cells.

PMID- 17456978
TI  - Biotransformations of lipoglycopeptides to obtain novel antibiotics.
AB  - The emergence of resistance among Gram-positive pathogens towards glycopeptide
      antibiotics has stimulated the research of second-generation molecules with
      improved activity and expanded antimicrobial spectrum. In this paper we
      investigate biotransformations as a way to generate novel teicoplanin- and A40926
      like molecules. A range of commercial enzymes, fungi and actinomycetes were
      tested on A40926 and on its semi-synthetic derivatives (MDL 63,246 and
      dalbavancin). Oxidation of dalbavancin to MDL 63,246 was achieved by Nonomuraea
      sp. ATCC 39727 and Actinomadura parvosata ATCC 53463, while Actinoplanes sp. NRRL
      3884, Actinoplanes missouriensis ATCC 23342 and Actinoplanes teichomyceticus ATCC
      31121 deacylated MDL 63,246, dalbavancin and A40926. It is worth noting that the
      actinomycetes able to catalyze the deacylation of lipoglycopeptides are
      themselves producers of microbiologically active glycopeptides. Structurally
      related antibiotics (mideplanin and teicoplanin) were not transformed.
      Biotransformation conditions were optimised and scaled-up for the use of
      Actinoplanes sp. NRRL 3884 in the production of novel deacylated derivatives.

PMID- 17456979
TI  - Isolation, structure elucidation and activity of an unknown impurity of
      amphotericin B.
AB  - An unknown impurity named amphotericin B (2) (AmB(2)) isolated from amphotericin
      B (AmB) bulk material was identified as
      (1S,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)
      33-[(3-amino-3,6-dideoxy-beta-D-mannopyranosyl)oxy]-1-methyloxy-3,5,6,9,11,17,37
      heptahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta
      19,21,23,25,27,29,31-heptaene-36-carboxylic acid according to the IUPAC. The
      structure was elucidated by various 1D and 2D NMR techniques, mass spectrometry
      and by comparison with the NMR data of AmB. Its activity against Candida albicans
      was evaluated by comparison with AmB.

PMID- 17456980
TI  - Elloxazinones A and B, New Aminophenoxazinones from Streptomyces griseus Acta
      2871.
AB  - Two new aminophenoxazinone compounds with antitumor activity, elloxazinone A and
      B, were isolated from the culture filtrate of Streptomyces griseus Acta 2871.
      Their chemical structures were determined by mass spectrometry, NMR spectroscopy
      and X-ray analysis. Elloxazinones A and B showed a moderate inhibition of the
      proliferation of human cells from gastric adenocarcinoma in vitro but a strong
      inhibition of hepatocellular carcinoma cells whereas elloxazinone B strongly
      inhibited the proliferation of human breast carcinoma cells.

PMID- 17456981
TI  - Serialynic acid, a new phenol with an isopentenyne side chain from Antrodia
      serialis.
AB  - A new phenolic compound serialynic acid was isolated from an agar culture of the
      basidiomycete Antrodia serialis, through bioactivity-guided fractionations. It
      showed weak growth inhibitory activity towards phytopathogenic fungi and a dose
      independent anti-Pythium graminicola activity.

PMID- 17456982
TI  - Serum adiponectin level as an independent predictor of mortality in patients with
      congestive heart failure.
AB  - BACKGROUND: Congestive heart failure (CHF) is associated with altered energy
      homeostasis and myocardial inflammation, hypertrophy, and fibrosis. Adiponectin,
      an insulin-sensitizing adipocytokine, may affect these pathogenic factors, and
      the circulating adiponectin level may serve as a biological marker of CHF. This
      study aimed to assess the significance of serum adiponectin as a prognostic
      marker for Japanese CHF patients. METHODS AND RESULTS: The serum adiponectin
      levels were compared between 54 (24 ischemic and 30 non-ischemic) CHF patients
      with left ventricular systolic dysfunction and 55 age- and gender-matched control
      subjects. The CHF patients also underwent simultaneous clinical assessment and
      measurements for brain natriuretic peptide (BNP) and parameters of lipid or
      glucose metabolism. Compared with the controls, the CHF patients showed
      significantly increased serum adiponectin levels [6.7 (4.9-12.6) vs 14.6 (9.7
      25.4) microg/ml, p<0.0001]. In the CHF patients, the log-transformed values of
      the serum adiponectin levels positively correlated with the log-transformed
      values of the plasma BNP levels (p=0.0003, r=0.48) and inversely correlated with
      the body mass index (p=0.0006, r=-0.46). Furthermore, an increase in the serum
      adiponectin level was associated with higher mortality (p<0.05), particularly in
      the ischemic CHF patients (p<0.005). CONCLUSIONS: An increase in the circulating
      adiponectin level was associated with higher mortality in the ischemic CHF
      patients. Adiponectin may be an informative risk marker for Japanese CHF
      patients.

PMID- 17456983
TI  - Cardiac troponin T vs other biochemical markers in patients with congestive heart
      failure.
AB  - BACKGROUND: Several pathologic processes can cause myocardial injury, which is
      followed by cardiac remodeling and congestive heart failure (CHF). Cardiac
      troponin T (cTnT), a specific and sensitive marker of myocardial injury, has been
      related to long-term outcome in patients with CHF, so the relationship between
      cTnT and other biochemical markers associated with the pathophysiology of CHF was
      investigated in the present study. METHODS AND RESULTS: Between February 2004 and
      December 2005, 145 consecutive hospitalized patients (mean left ventricular
      ejection fraction (LVEF) 31.6+/-0.9%) with CHF were divided into low (<0.01
      ng/ml) and high (> or =0.01 ng/ml) serum cTnT groups. Correlations with other
      prognostic biochemical markers, including brain natriuretic peptide (BNP), type I
      collagen C-terminal telopeptide (ICTP), procollagen type III peptide (PIIIP),
      renin, norepinephrine (NOREPI), C-reactive protein (CRP), cholesterol, hemoglobin
      (Hb), uric acid and HbA1c were examined. cTnT was high in 46 (32%) and low in 99
      (68%) patients at baseline. Patients with high cTnT had abnormally high blood
      concentrations of BNP (p<0.0001), ICTP (p<0.0001), PIIIP (p=0.0006), NOREPI
      (p=0.0119), CRP (p=0.0003), uric acid (p=0.0026) and HbA1c (p=0.0361). In
      contrast, concentrations of cholesterol and Hb were significantly lower in
      patients with high cTnT (p=0.0319 and 0.0005, respectively). Death from or
      rehospitalization for CHF occurred in 41% in the high vs 9% in the low cTnT group
      (p=0.0002). Univariate analysis showed that high cTnT (p=0.0005), BNP (p=0.0001),
      renin (p=0.0158), NOREPI (p=0.0094), old age (p=0.0390), low LVEF (p=0.0231) and
      high New York Heart Association (NYHA) class (p=0.0006) were predictors of death
      from or rehospitalization for CHF. By multivariate analysis including BNP,
      NOREPI, age, LVEF and NYHA class, high cTnT and renin remained as significant
      predictors. CONCLUSIONS: Patients with ongoing myocardial injury and high cTnT
      had associated findings consistent with activation of the sympathetic system,
      synthesis of cardiac fibrosis, inflammation and metabolic abnormalities. By
      multivariate analysis, high cTnT and renin remained significant predictors of
      death or rehospitalization.

PMID- 17456984
TI  - Electrophysiologic and anatomical characteristics of the right atrial posterior
      wall in patients with and without atrial flutter: analysis by intracardiac
      echocardiography.
AB  - BACKGROUND: The posterior right atrial transverse conduction capability during
      typical atrial flutter (AFL) is well known, but its relationship to the
      anatomical characteristics remains controversial. METHODS AND RESULTS: Thirty
      four AFL and 16 controls underwent intracardiac echocardiography after placement
      of a 20-polar catheter at the posterior block site during AFL or pacing. In 31
      patients, the effective refractory period (ERP) at the block site was determined
      as the longest coupling interval that resulted in double potentials during
      extrastimuli from the mid-septal (SW) and free (FW) walls. The block site was
      located 3.0-29.0 mm posterior to the crista terminalis (CT) in each AFL and
      control patient. The CT area indexed to the body surface area was larger in AFL
      patients than in control patients (16.4+/-6.5 mm(2)/m(2) vs 11.3+/-6.4
      mm(2)/m(2), p=0.01), and was positively correlated to age (r=0.34, p=0.02). The
      ERP was longer in the AFL patients than in controls (SW: median value 600 [270
      725] ms vs 220 [200-253] ms; FW: 280 [230-675] ms vs 215 [188-260] ms, p<0.05 for
      each). CONCLUSIONS: A functional block line was located on the septal side of the
      CT in all patients. A limited conduction capability and age-related CT
      enlargement might have important implications for the pathogenesis in AFL.

PMID- 17456985
TI  - Assessment of the histological characteristics of coronary arterial plaque with
      severe calcification.
AB  - BACKGROUND: Several studies have shown that rotational atherectomy (RA) is
      associated with higher rates of the slow-flow phenomenon and that ablated
      particles may be the possible cause. Intravascular ultrasound (IVUS) has an
      intrinsic limitation in assessing plaque morphology behind the calcification
      because of acoustic shadowing. Therefore, the purpose of this study was to
      investigate plaque characteristics behind severe calcification by histological
      examination. METHODS AND RESULTS: One hundred eight coronary arterial segments
      from 40 human cadavers (24 males, 16 females, mean age 74+/-7 years) were
      examined. Serial images of IVUS were obtained and 18 severe calcified lesions
      were collected. Experienced observers quantitatively analyzed the lesions by
      computerized planimetry for fibrous, fibrofatty, calcification, and necrotic
      tissue area. Histologically, 15 of 18 severely calcified lesions (83%) had an
      extensive necrotic tissue containing large numbers of cholesterol crystals and
      microcalcifications; 16 of same 18 severely calcified lesions (89%) had
      fibrofatty tissue as well as calcification. The necrotic tissue occupied 14+/-13%
      and fibrofatty tissue occupied 13+/-11% of severely calcified lesions.
      CONCLUSION: Necrotic core and fibrofatty tissue components "hidden" behind
      calcification might cause emboli-induced thrombus formation and distal flow
      disturbance during RA.

PMID- 17456986
TI  - Atherosclerotic plaque with ultrasonic attenuation affects coronary reflow and
      infarct size in patients with acute coronary syndrome: an intravascular
      ultrasound study.
AB  - BACKGROUND: No reflow following percutaneous coronary intervention (PCI) is a
      major concern in patients with acute coronary syndrome (ACS) and it may be
      influenced by the preexisting plaque type. METHODS AND RESULTS: To evaluate the
      impact of plaque characteristics on coronary reflow following PCI in patients
      with ACS, a total of 110 patients (89 acute myocardial infarction, 21 unstable
      angina) were assessed by intravascular ultrasound. Plaque type was categorized as
      either atherosclerotic plaque without ultrasonic attenuation (group 1) or
      atherosclerotic plaque with attenuation (group 2). External elastic membrane,
      plaque plus media, and lumen area were measured. Coronary flow was assessed by
      Thrombolysis in Myocardial Infarction (TIMI) grade and TIMI frame count. Although
      the final TIMI frame count was similar between the 2 groups, TIMI frame count
      immediately after the first balloon inflation was significantly higher in group 2
      (p=0.03). Despite the similar final TIMI grade and TIMI frame count, peak
      creatine kinase level was significantly higher (3,035+/-2,553 vs 1,950+/-1,958
      IU/L, p=0.04) and fatal arrhythmia more frequently observed (16.4% vs 2.7%,
      p=0.04) in group 2 than in group 1. CONCLUSIONS: Atherosclerotic plaque with
      ultrasonic attenuation may be related to a transient deterioration in coronary
      flow and as a result larger infarct size and higher incidence of fatal arrhythmia
      following PCI in patients with ACS. These results may help in selecting lesions
      suitable for distal protection devices.

PMID- 17456987
TI  - Relationship between coronary artery remodeling and plaque composition in culprit
      lesions: an intravascular ultrasound radiofrequency analysis.
AB  - BACKGROUND: The relationship between coronary artery remodeling and culprit
      plaque composition in vivo has not been fully evaluated by spectral analysis of
      intravascular ultrasound (IVUS) radiofrequency (RF) data. METHODS AND RESULTS:
      IVUS RF analyses were performed for 56 consecutive de novo culprit lesions of 52
      patients undergoing percutaneous coronary intervention. Remodeling of culprit
      lesions was determined using the remodeling index (RI), calculated as the
      external elastic membrane area of the minimum lumen area (MLA) site divided by
      that of the proximal reference site. Positive remodeling was defined as RI >1.05,
      intermediate remodeling as 0.95< or = RI < or =1.05 and negative remodeling as RI
      <0.95. Among the 56 lesions, positive remodeling was detected in 24, intermediate
      remodeling in 16, and negative remodeling in 16. At MLA sites, positive
      remodeling lesions had a larger percentage of the fibrofatty component than
      negative remodeling lesions (22.5+/-10.3% vs 10.4+/-6.6%, p=0.0001), whereas the
      latter contained a larger percentage of the dense calcium component than the
      former (2.8+/-2.9% vs 8.4+/-7.0%, p=0.016). CONCLUSIONS: Culprit plaques with
      positive remodeling have a large lipid burden, whereas those with negative
      remodeling contain a large amount of calcium.

PMID- 17456988
TI  - Augmentation of left ventricular apical endocardial rotation with inotropic
      stimulation contributes to increased left ventricular torsion and radial strain
      in normal subjects: quantitative assessment utilizing a novel automated tissue
      tracking technique.
AB  - BACKGROUND: The difference in the left ventricular (LV) torsion of the endo- and
      epicardium (Endo, Epi) with inotropic stimulation and its relation to radial
      strain (RS) remain unclear. METHODS AND RESULTS: LV basal and apical short-axis
      images were recorded in 13 normal subjects at rest and during dobutamine infusion
      (5, 10 microg x kg (-1) x min(-1)). A total of 8 points (anterior, lateral,
      posterior and septum in both Endo and Epi) were manually placed by 2-dimensional
      tissue tracking technique and the movement of these points during a cardiac cycle
      was tracked, after which the rotation angles and RS were calculated. LV torsion
      was defined as the net difference between the basal and apical rotations. In the
      LV apex, Endo-rotation increased (7.8+/-2.7 to 14.1+/-4.6 degrees, p<0.01),
      whereas Epi-rotation was unchanged, with dobutamine. The apical Endo-rotation was
      significantly greater than the Epi-rotation, although no difference was seen
      between the Endo and Epi in the LV base throughout the study. During dobutamine
      infusion, the LV Endo-torsion increased (9.5+/-2.8 to 19.3+/-4.8 degrees, p<0.01)
      and these values were greater than those for Epi. The apical RS increased with
      the dobutamine dose (39.0+/-9.3 to 61.9+/-15.5%, p<0.01), whereas basal RS
      initially increased at 5 microg x kg(-1) x min(-1), but thereafter showed no
      further increase at 10 microg x kg(-1) x min(-1) of dobutamine. CONCLUSIONS:
      Augmentation of LV rotation with inotropism was clearly observed in the apical
      Endo, thus causing increased LV endo-torsion and apical RS.

PMID- 17456989
TI  - Preload dependency of the time interval between the onset of mitral inflow and
      the early diastolic annular motion: a hemodialysis-related preload reduction
      study.
AB  - BACKGROUND: The novel parameter T(E-E'), which is the time interval between the
      onset of the early diastolic mitral inflow velocity (E) and the early diastolic
      mitral annular velocity (E'), is reported to be related to the constant of the
      left ventricular (LV) relaxation, and T(E-E') is also reported to be useful for
      predicting the LV filling pressure. METHODS AND RESULTS: To investigate the
      effect of preload reduction via hemodialysis on T(E-E'), 28 pairs of
      echocardiographic evaluations were performed just before and immediately after
      hemodialysis, including the measurement of the T(E-E') as well as measurement of
      the conventional echocardiographic parameters. The baseline T(E-E') was 17.9 +/
      28.1 ms, which correlated with the ratio of E/E' (r=0.49, p=0.008). After
      hemodialysis, T(E-E') was shortened to -3.2+/-34.1 ms, which was a significant
      change from baseline (p=0.001). CONCLUSIONS: As T(E-E') is a preload dependent
      parameter, the intravascular volume status should be taken into account when the
      clinical application of T(E-E') is considered as an index of LV relaxation.

PMID- 17456990
TI  - Relationship of serum adiponectin level to adverse cardiovascular events in
      patients who undergo percutaneous coronary intervention.
AB  - BACKGROUND: Hypoadiponectinemia has been reported to indicate an increased risk
      of cardiovascular disease, so the present study investigated the significance of
      serum adiponectin (APN) levels for predicting clinical outcomes after
      percutaneous coronary intervention (PCI). METHODS AND RESULTS: The APN levels
      were evaluated in 184 consecutive patients who underwent PCI. The patients were
      divided into Group A [the lowest quartile of APN levels (APN < or =4.5
      microg/ml), n=46] and Group B [the upper 3 quartiles of APN levels (APN >4.5
      microg/ml), n=138]. During a mean follow-up period of 27.3 months, the rate of
      major adverse cardiac and cerebrovascular events (MACCE: death from any cause, re
      infarction, repeat coronary revascularization, hospitalization because of
      congestive heart failure, and cerebral infarction) was higher in Group A (58.7%)
      than in Group B (37.0%, p=0.0101). Moreover, when the APN levels were calculated
      by adjusting for sex, age, body mass index, and triglyceride levels, patients in
      the lowest quartile of residual APN levels had a higher risk of MACCE (p=0.0405).
      Multiple logistic analyses showed that hypoadiponectinemia (APN < or =4.5
      microg/ml) was independently correlated with MACCE. Kaplan-Meier analysis
      demonstrated a higher MACCE rate in Group A than in Group B (Log-rank
      chi(2)=7.89, p=0.0050). CONCLUSION: The APN level may be helpful for predicting
      clinical outcomes after PCI.

PMID- 17456991
TI  - Elevated plasma levels of oxidized low-density lipoprotein relate to the presence
      of angiographically detected complex and thrombotic coronary artery lesion
      morphology in patients with unstable angina.
AB  - BACKGROUND: Increased levels of oxidized low-density lipoprotein (ox-LDL) are
      related to plaque instability, so the aim of the present study was to investigate
      whether there is a relationship between angiographic coronary plaque morphology
      in patients with unstable angina pectoris (UAP) and the level of ox-LDL. METHODS
      AND RESULTS: Plasma ox-LDL levels were measured in 149 patients with UAP and in
      88 control subjects, using a highly sensitive enzyme-linked immunosorbent assay
      method. Angiographic morphology of the culprit lesion was classified as either
      simple or complex based on the Ambrose classification. Plasma ox-LDL levels in
      patients with Braunwald class III were significantly higher than in patients with
      class I (p<0.0001) or in control subjects (p<0.0001). In each of the 3 Braunwald
      classes, plasma ox-LDL levels in patients with a complex lesion were
      significantly higher than in patients with a simple lesion. Multivariate logistic
      regression analysis revealed that ox-LDL level and Braunwald class III were
      independent factors associated with angiographically detected complex lesions.
      CONCLUSION: In each Braunwald class of UAP, elevated plasma levels of ox-LDL
      closely relate to the presence of angiographically detected complex and
      thrombotic lesion morphology.

PMID- 17456992
TI  - Association of high levels of plasma free dopamine with future coronary events in
      patients with coronary artery disease.
AB  - BACKGROUND: There is an intimate relationship between activation of the
      sympathetic nervous system and myocardial ischemia. This study examined whether
      plasma levels of dopamine, a precursor of norepinephrine, may provide prognostic
      information in coronary artery disease (CAD). METHODS AND RESULTS: Plasma levels
      of free dopamine were measured by high-performance liquid chromatography in 210
      consecutive patients with stable CAD. The patients were prospectively followed up
      for a period of < or =36 months until occurrence of a clinical coronary event.
      Coronary events occurred in 37 patients during follow-up. In Kaplan-Meier
      survival analysis, higher dopamine levels (> or =30 pg/ml) resulted in a higher
      event probability (p<0.01). Multivariate Cox hazards analysis showed that higher
      dopamine levels were a significant and independent risk factor for future
      coronary events (hazard ratio 3.3, 95% confidence interval 1.3-8.1, p<0.01).
      Furthermore, patients with higher dopamine levels had lower left ventricular (LV)
      ejection fraction and higher levels of brain natriuretic peptide, C-reactive
      protein, and fibrinogen than those with lower dopamine levels. CONCLUSIONS:
      Plasma levels of free dopamine are increased in association with a decrease in LV
      function and an increase in inflammatory risk markers. Higher free dopamine
      levels are an independent risk factor for future coronary events in CAD patients.

PMID- 17456993
TI  - Plasma level of mitochondrial coupling factor 6 increases in patients with
      coronary heart disease.
AB  - BACKGROUND: The aim of the present study was to investigate alterations in the
      plasma level of coupling factor 6 (CF6), a novel endogenous inhibitor of
      prostacyclin, in patients with coronary heart disease. METHODS AND RESULTS: In
      total, 35 patients with coronary heart disease and 20 age-matched healthy
      subjects were examined. Plasma levels of CF6 and 6-keto-prostaglandin (PG)F(1a)
      (a stable metabolite of prostacyclin) were measured using radioimmunoassay. The
      plasma level of CF6 was significantly increased in patients (254.1+/-29.8 pg/ml
      vs 219.4 +/-36.7 pg/ml in controls, p<0.0001), whereas that of 6-keto-PGF(1a) was
      significantly decreased (23.4 +/-2.3 pg/ml vs 26.1+/-4.5 pg/ml in controls,
      p=0.001). Moreover, after percutaneous transluminal coronary angioplasty (PTCA)
      and stent therapy, the level of CF6 was further increased by 30% to 330.4+/-26.0
      pg/ml, and that of 6-keto-PGF (1a) was decreased by 42% to 13.5+/-2.0 pg/ml,
      compared with baseline (all p<0.01). Univariate analysis showed a significant
      result that the plasma level of CF6 was inversely correlated with that of 6-keto
      PGF(1a) in the patients. The plasma ratio of CF6 to 6-keto-PGF(1a) was 8.4 in the
      control group and that in patients with coronary heart disease was increased to
      24.4 after the therapy from 10.9 before therapy. CONCLUSIONS: The results suggest
      that an increased CF6 level may be responsible in part for the decreased
      prostacyclin level observed in patients with coronary heart disease, in
      particular after PTCA and stent therapy. As a potential risk factor for coronary
      heart disease, CF6 might have important clinical significance.

PMID- 17456994
TI  - Relationship between endothelial function and coronary risk factors in patients
      with stable coronary artery disease.
AB  - BACKGROUND: Results of experimental and clinical studies suggest that both
      coronary artery disease (CAD) itself and its traditional risk factors lead to
      endothelial dysfunction. The aim of the present study was to determine which CAD
      risk factors sustain their contribution to endothelial dysfunction despite the
      presence of established CAD. METHODS AND RESULTS: The study group comprised 150
      patients with CAD. Using a high-resolution ultrasound, the diameter of the
      brachial artery at rest and during reactive hyperemia (flow-mediated dilatation,
      FMD%: endothelial-dependent stimulus to vasodilatation), as well as after
      sublingual administration of nitroglycerin (NTG%: endothelium-independent
      vasodilatation), was measured. The relationship between FMD% and coronary risk
      factors [diabetes mellitus (DM), total cholesterol, high-density lipoprotein
      cholesterol, low-density lipoprotein-cholesterol, triglycerides, age, family
      history of premature atherosclerosis, smoking, hypertension (HT), body mass index
      (BMI)] was investigated. In univariate analysis there was an inverse relationship
      between FMD% and age (r=-0.300, p<0.001), and BMI (r=-0.230, p<0.005) and FMD%
      was significantly lower in diabetic patients when compared to non-diabetic
      patients (p<0.001). In stepwise multivariate regression analysis; FMD still
      correlated with DM and advanced age, but not with BMI (beta=0.065, p<0.001, beta=
      0.001 p=0.002, beta=-0.087, p<0.284, respectively). FMD% was found to be not
      associated with hypercholesterolemia, family history of premature
      atherosclerosis, HT and smoking. CONCLUSION: Only aging and DM were independently
      associated with endothelial dysfunction in patients with established CAD.

PMID- 17456995
TI  - Level and value of interleukin-18 in patients with acute myocardial infarction
      undergoing primary coronary angioplasty.
AB  - BACKGROUND: The prognostic value of interleukin (IL)-18 in patients with ST
      segment elevation acute myocardial infarction (STEMI) is currently unclear. Thus,
      the purpose of this study was to test whether the circulating IL-18 level can
      predict prognosis in patients with STEMI undergoing primary percutaneous coronary
      intervention (PCI). METHODS AND RESULTS: A prospective cohort study was conducted
      with 267 consecutive patients with STEMI of onset <12 h who were undergoing
      primary PCI. Blood samples for plasma IL-18 level were collected in the
      catheterization laboratory following vascular puncture. The plasma IL-18 level
      was also evaluated in 25 healthy and 30 at-risk control subjects. The plasma
      level of IL-18 was significantly higher in acute myocardial infarction (AMI)
      patients than in both groups of control subjects (all p<0.0001). Patients with
      high plasma IL-18 level (> or =560 pg/ml) had significantly higher peak creatine
      kinase-MB levels, higher incidence of cardiogenic shock upon presentation,
      significantly lower left ventricular ejection fraction (LVEF), lower successful
      reperfusion and significantly higher incidence of 30-day composite major adverse
      clinical events (MACE) (advanced congestive heart failure > or = class 3 or 30
      day mortality) than those patients with low plasma IL-18 level (<560 pg/ml) (all
      p<0.0001). Multiple stepwise logistic regression analysis demonstrated that high
      plasma IL-18 level (> or =560 pg/ml) along with low LVEF (<50%) and cardiogenic
      shock were the most independent predictors of 30-day MACE (p<0.0001).
      CONCLUSIONS: In patients with STEMI, plasma IL-18 level is a major independent
      inflammatory predictor of 30-day MACE. Evaluation of circulating IL-18 might
      improve the prediction of unfavorable clinical outcomes following AMI.

PMID- 17456997
TI  - Left ventricular hypertrophy and geometry in untreated essential hypertension is
      associated with blood levels of aldosterone and procollagen type III amino
      terminal peptide.
AB  - BACKGROUND: The present study examined the role of aldosterone in left
      ventricular hypertrophy (LVH) and geometry in patients with untreated essential
      hypertension (EHT), and investigated the contribution of myocardial fibrosis to
      the process of LVH. METHODS AND RESULTS: The relationship of the plasma
      aldosterone concentration (PAC) to LVH and left ventricular (LV) geometry was
      investigated in 57 consecutive patients with untreated EHT. PAC correlated with
      both LV mass index (LVMI: r=0.46, p=0.0004) and relative wall thickness (RWT:
      r=0.33, p=0.013). In patients with LVH (LVMI > or =125 g/m(2)), the serum
      concentration of procollagen type III amino-terminal peptide (PIIINP), a marker
      of myocardial fibrosis, correlated with RWT (r=0.46, p=0.029). These patients
      were divided into 2 groups: concentric hypertrophy (CH) with RWT > or =0.44, and
      eccentric hypertrophy (EH) with RWT <0.44. The serum PIIINP concentration was
      significantly higher in the CH group than in the EH group (0.52+/-0.02 ng/ml vs
      0.44+/-0.03 ng/ml, respectively; p<0.05). CONCLUSIONS: Aldosterone may be
      involved in LVH and LV geometry, particularly in the development of CH.
      Myocardial fibrosis seems more strongly involved in the hypertrophic geometry of
      CH than with EH.

PMID- 17456996
TI  - Coronary artery aneurysm induced by Kawasaki disease in children show features
      typical senescence.
AB  - BACKGROUND: Kawasaki disease (KD) causes coronary artery disease (CAD) in
      children. In addition, a history of KD is suspected to be a risk factor for the
      development of atherosclerotic heart disease in the future. Histological
      senescence changes are a common denominator in atherosclerotic lesions in adults,
      so the present study investigated whether histological senescence changes had
      already occurred in KD aneurysm. METHODS AND RESULTS: KD coronary aneurysms and
      internal mammary arteries retrieved from 5 children with KD (3, 4, 5, 6, and 11
      years old, respectively) who underwent coronary artery bypass grafting, as well
      as giant coronary aneurysm size-reducing operations, were analyzed. Senescence
      associated strong beta-galactosidase activity was observed in KD aneurysms, but
      not in the internal mammary arteries. An immunohistochemical analysis of the KD
      aneurysm using anti-CD31, anti-endothelial nitric oxide synthetase (eNOS), anti
      vascular adhesion molecule-1 (VCAM-1), and anti-monocyte chemoattractant protein
      1 (MCP-1) showed vascular endothelium CD31 staining, decreased staining of eNOS
      and strong staining of MCP-1 and VCAM-1. cDNA microarray gene expression
      profiling revealed increased MCP-1 expression in the KD aneurysm, a finding
      confirmed by quantitative polymerase chain reaction. CONCLUSIONS: Histological
      features of senescence and active remodeling gene expression show that the KD
      aneurysm is not a silent vasculitis terminal. The future fate of KD aneurysms,
      including atherosclerosis, should be monitored carefully.

PMID- 17456998
TI  - Adolescent obesity adversely affects blood pressure and resting heart rate.
AB  - BACKGROUND: Obesity is associated with hypertension (HT) and high resting heart
      rate (HR), as well as metabolic disturbances. However, little is known about how
      strongly these hemodynamic abnormalities are associated with the degree of
      obesity in adolescents. METHODS AND RESULTS: Height, body weight, resting HR, and
      systolic and diastolic blood pressures were measured in 20,165 male and 19,683
      female high-school students. Adiposity levels were classified into 6 groups by
      body mass index: group 1 (<20th percentile), group 2 (20th-39.9th percentile),
      group 3 (40th-59.9th percentile), group 4 (60th-79.9th percentile), group 5 (80th
      98.9th percentile), and group 6 (> or =99th percentile). Systolic and diastolic
      hypertensions were defined as > or =140 mmHg and > or =85 mmHg, respectively.
      Resting tachycardia was defined as the corresponding 95th percentile or greater.
      Resting HR and systolic and diastolic blood pressures increased with adiposity
      level in both sexes (p<0.0001). Both systolic HT and diastolic HT were associated
      with high resting HR, and the clustering of these unfavorable conditions
      increased with the degree of obesity. CONCLUSION: Hemodynamic abnormalities, such
      as HT and a high resting HR, are closely associated with adolescent obesity and
      are probably explained by impaired autonomic nerve function.

PMID- 17456999
TI  - Aortic elastic properties in patients with hypertensive response to exercise.
AB  - BACKGROUND: The aim of this study was to evaluate whether there is a relationship
      between aortic elastic properties in patients with a suggestive response to
      treadmill exercise testing. METHODS AND RESULTS: The study group comprised 32
      patients suggesting hypertensive response to exercise and 20 patients suggesting
      normal blood pressure response to treadmill exercise testing. Baseline
      demographic characteristics were similar in both groups. However, the mean aortic
      stiffness index of patients suggesting hypertensive response to treadmill
      exercise testing was significantly higher (4.8+/-1.26 vs 2.36+/-1.09; p=0.001)
      whereas aortic distensibility was significantly lower (12.82 +/-5.84 vs 22.64+/
      14.54; p=0.001) than the control group. The aortic strain of patients with
      hypertensive response to exercise was lower than the control group (12+/-3% vs
      19.2+/-5%, p<0.001). The left ventricular mass (LVM) of these patients was also
      higher than control group (206.5+/-46.3 vs 134.2+/-19.97; p=0.01). A negative
      correlation between LVM and distensibility was found (r=-0.64; p=0.001) well as a
      positive correlation between LVM and aortic stiffness index (r=0.51; p=0.004) in
      patients suggesting hypertensive response to exercise. Pressure--rate product was
      also found to be correlated with LVM (r=0.47; p=0.006). CONCLUSION: Elastic
      properties of the aorta may be impaired in subjects showing exaggerated blood
      pressure response to exercise long before clinically manifest hypertension,
      particularly if the LVM is increased.

PMID- 17457000
TI  - Evaluation of hypertensive cardiac abnormalities using the Cornell product.
AB  - BACKGROUND: The Cornell product (CP) improved identification of left ventricular
      hypertrophy (LVH) in the LIFE study, although its clinical significance is still
      unknown in Japanese hypertensive (HT) patients. METHODS AND RESULTS: A standard
      12-lead ECG was recorded in 265 HT and 363 normotensive cases (N). All ECGs were
      digitized, and a simple product was calculated by multiplying the Cornell voltage
      (CV) by the QRS duration. In 147 of the 265 HT cases, the standard 12-lead ECG
      and transthoracic Doppler echocardiography were examined in the same period. The
      mean value of CP increased in the following order: 1,426+/-673 mm x ms in N,
      1,989+/-900 mm x ms in HT with treatment, 2,137+/-976 mm x ms in HT without
      treatment. The correlation with left ventricular mass index (LVMI) measured by
      echocardiography was improved by CP with the simple CV. With use of a partition
      of 2,440 mm x ms in CP, LVMI and relative wall thickness were significantly
      higher in HT with > or =2,440 mm x ms of CP compared with <2,440 mm x ms. Early
      diastolic wave in tissue Doppler imaging was significantly lower in HT with > or
      =2,440 mm x ms of CP compared with <2,440 mm x ms. CONCLUSION: The Cornell
      product is a useful ECG marker, reflecting not only left ventricular (LV) mass
      but also LV geometry and diastolic function in Japanese HT patients.

PMID- 17457001
TI  - Measurement of flow-mediated vasodilation of the brachial artery: a comparison of
      measurements in the seated and supine positions.
AB  - BACKGROUND: Measurement of flow-mediated vasodilation (FMD) is used to assess
      endothelial function in humans and according to the guidelines, subjects must
      remain supine during the study. However, measurement of FMD while seated would be
      more comfortable and convenient for patients, so the purpose of this study was to
      determine the effect of the patient's position on FMD results. METHODS AND
      RESULTS: High-resolution ultrasonography, a linear array transducer (13 MHz) and
      an arm-holding device were used to measure arterial diameter in response to
      reactive hyperemia (FMD, cuff inflated to 50 mmHg above systolic blood pressure
      for 5 min) and in response to sublingual nitroglycerine (NTG, 75 microg) in 31
      subjects, which included those with cardiovascular diseases. There was no
      significant difference between basal or peak hyperemic blood flow in the seated
      or supine position. Basal brachial artery diameter, FMD and vascular response to
      NTG were similar in both positions (basal diameter: 3.8+/-0.4 vs 3.9+/-0.4 mm,
      FMD: 7.3+/-4.3% vs 7.2+/-4.5%, NTG: 13.1+/-5.1% vs 12.8+/-5.6%). CONCLUSIONS: The
      findings suggest that measurement of FMD in the seated position is as useful as
      measuring it in the supine position for assessing endothelial function. This
      flexibility of position is better for patients and physicians, and should lead to
      more widespread measurement of FMD.

PMID- 17457002
TI  - Apolipoprotein A-I/C-III/A-IV SstI and apolipoprotein B XbaI polymorphisms do not
      affect early functional and structural changes in atherosclerosis: the
      Cardiovascular Risk in Young Finns study.
AB  - BACKGROUND: The present study was designed to investigate the effects of apoB
      XbaI and apoA-I/C-III/A-IV SstI polymorphisms to carotid artery intima-media
      thickness (IMT), carotid artery compliance (CAC) and brachial artery flow
      mediated vasodilatation (FMD). METHODS AND RESULTS: As part of the Cardiovascular
      Risk in Young Finns Study, the carotid IMT, CAC and brachial FMD of 2,265
      subjects (mean age +/- SD 32 +/-5 years) were measured with ultrasonography, and
      genotyping of the apolipoprotein polymorphisms was performed. The frequencies of
      the genotypes did not differ between the groups with high (above median 0.57 mm)
      and low (below median) IMT, CAC or FMD. The average carotid IMT differed between
      the 3 apoB XbaI genotypes (ANOVA, p=0.04), but not between the apoA-I/C-III/A-IV
      SstI genotypes (ANOVA, p=0.53). The relationship between the polymorphisms and
      carotid IMT was not significant in any of the covariate-adjusted logistic and
      linear regression analyses. CAC and FMD were not influenced by either of the
      polymorphisms in ANOVA and regression analyses. CONCLUSIONS: The polymorphisms
      apoA-I/C-III/A-IV SstI and apoB XbaI do not seem to affect carotid artery
      characteristics or brachial artery FMD in young adulthood.

PMID- 17457003
TI  - Strong linkage disequilibrium and association of -1131T>C and c.553G>T
      polymorphisms of the apolipoprotein A5 gene with hypertriglyceridemia in a
      Japanese population.
AB  - BACKGROUND: The apolipoprotein A5 gene (ApoA5) plays an important role in
      modulating triglyceride metabolism. Polymorphisms of ApoA5, including -1131T>C
      and c.553G>T (G185C), have been reported to correlate with hypertriglyceridemia
      (HTG). In the present study the relationships of 5 single nucleotide
      polymorphisms, including the -1131T>C, c.56C>G, IVS3+476G>A, c.553G>T, and
      c.1259T>C polymorphisms of ApoA5, with HTG were investigated. METHODS AND
      RESULTS: The study group comprised 95 Japanese patients with HTG and 119
      unrelated normolipidemic subjects. Frequencies of the C allele of -1131T>C
      (0.511) and the T allele of c.553G>T (0.205) in the hypertriglyceridemic patients
      were significantly higher than in the normolipidemic subjects (0.315 and 0.105,
      respectively). The c.56C>G (S19W) polymorphism was not observed, and the other 4
      polymorphic sites were in strong linkage disequilibrium. Five of the 8 detected
      haplotypes with the C allele of -1131T>C correlated with HTG. Promoter activities
      of ApoA5, including that with the -1131T>C polymorphism, were estimated using a
      luciferase assay. Analysis of ApoA5 promoters showed that the -1131T>C
      polymorphism alone had no effect. Comparison of expression of mutant G185C and
      wild-type ApoA5-green fluorescent protein (GFP) in HepG2 cells showed that ApoA5
      GFP was abundant in punctate endosome-like structures, and ApoA5 (G185C)-GFP
      expression resembled that of the wild type. CONCLUSIONS: The -1131T>C and
      c.553G>T (G185C) polymorphisms correlated with HTG in this Japanese population,
      but neither polymorphism directly affected ApoA5 expression.

PMID- 17457004
TI  - Segmental pulmonary vein antrum isolation using the "large-size" lasso catheter
      in patients with atrial fibrillation.
AB  - BACKGROUND: The limited efficacy and complications of segmental ostial pulmonary
      vein isolation (PVI) for treating atrial fibrillation (AF) have been discussed
      so, in the present study the feasibility and efficiency of performing segmental
      pulmonary vein (PV) antrum isolation to treat AF were assessed. METHODS AND
      RESULTS: A total of 187 patients with drug-refractory AF (paroxysmal 120,
      persistent 67) underwent segmental PVI guided by circumferential 20-electrode
      catheters (Lasso). Radiofrequency (RF) current was delivered either at the ostium
      using a regular Lasso (15-20 mm in diameter, 70 patients: Group 1) or at the
      antrum using a larger Lasso (25-30 mm in diameter, 117 patients: Group 2). A
      significantly wider region had to be ablated, with a longer RF application time,
      to isolate all 4 PVs in Group 2 patients than in Group 1 patients. Although the
      rate of recurrence of AF after the initial session was equal in both groups, a
      significantly greater number of patients were free from AF after a mean of 1.4
      procedures in Group 2 than in Group 1 (93% vs 76% for paroxysmal AF, 78% vs 48%
      for persistent AF). CONCLUSIONS: Segmental antral PVI using large-sized Lasso
      catheters was found to be more effective and safer than ostial PVI for the
      treatment of AF.

PMID- 17457005
TI  - Incidence of major bleeding complication of warfarin therapy in Japanese patients
      with atrial fibrillation.
AB  - BACKGROUND: During anticoagulation for prevention of stroke in patients with non
      valvular atrial fibrillation (NVAF), bleeding is the most serious complication.
      In Western countries, the incidences of major bleeding and intracranial
      hemorrhages with low-dose warfarin are known to occur at a rate of 0.4-1.3% and
      0.2% per year, respectively. The purpose of this study was to investigate the
      incidence and risk factors for major bleeding related with warfarin therapy in
      Japanese patients with NVAF. METHODS AND RESULTS: From August 2004 to July 2005,
      667 NVAF patients treated with warfarin for NVAF were followed-up. The target
      prothrombin time-international normalized ratio (PT-INR) value was set at 1.6-2.6
      (low-dose warfarin). The exposure on warfarin was 503 patient-years (average PT
      INR 2.00 +/-0.40). During the follow-up period, 12 major bleeding complications
      occurred (2.38% per patient-year), which included 3 intracranial hemorrhages
      (0.60% per patient-year). Among the patients' characteristics, average PT-INR >
      or =2.27 during the study was identified as an independent risk factor for major
      bleeding. CONCLUSIONS: The incidence of major bleeding and intracranial
      hemorrhages in Japanese NVAF patients with low-dose warfarin therapy was 2.38%
      and 0.60% per patient-year, respectively, which is higher than in Westerners.

PMID- 17457006
TI  - Fever associated with acute aortic dissection.
AB  - BACKGROUND: Although fever is a common accompanying feature of acute aortic
      dissection, few reports have been published concerning the duration and character
      of this fever. METHODS AND RESULTS: The mean duration of fever was calculated for
      a total of 57 patients with acute aortic dissection, who were then divided into 2
      groups: those with duration of fever shorter than the mean (Group A) and those
      with duration of fever equal to or longer than the mean (Group B). The reduction
      in false lumen size and hematological parameters were compared between groups.
      The mean duration of fever was 15.9+/-11 days. The false lumen reduction ratio
      was significantly higher in Group A (18.3+/-5.0%) than in Group B (2.0+/-5.3%).
      There was a significant negative correlation between the false lumen reduction
      ratio and duration of fever. Hematological parameters did not differ
      significantly between the 2 groups except for fibrin degradation product,
      although the white blood cell count and platelet counts and C-reactive protein
      concentration tended to be higher in Group B. CONCLUSIONS: Checking for fever is
      important in assessing the status of individual cases of acute aortic dissection.

PMID- 17457007
TI  - Unusual pulmonary embolism: septic pulmonary embolism and amniotic fluid
      embolism.
AB  - BACKGROUND: Septic and amniotic fluid emboli are rare sources of pulmonary
      embolism (PE), so the present study sought to elucidate the background of these
      cases. METHODS AND RESULTS: A total of 11,367 PE cases were identified from
      396,982 postmortem examinations. The incidence of septic PE was 247 (2.2%) of the
      total. The origin of infection was found in 85.6% of the cases. Fungal embolus
      was detected more often than bacterial embolus. The most frequently detected
      fungus was aspergillus (20.8%). The primary disease associated with fungal
      embolus was leukemia (43.2%). The incidence of PE cases associated with pregnancy
      and/or delivery was 89 (0.8%) of the total PE cases. Among them, amniotic fluid
      embolism was found in 33 (73.3%) of 45 PE cases with vaginal delivery, and in 7
      (21.2%) of 33 PE cases with cesarean delivery (p<0.0001). CONCLUSION: Fungal
      embolus was more frequent than bacterial embolus, and leukemia was most frequent
      as the primary disease in cases of fungal embolus. The main cause of PE in
      cesarean section cases was thrombotic embolism, and the main cause in vaginal
      delivery cases was amniotic fluid embolism.

PMID- 17457008
TI  - Associations of obesity measures with metabolic risk factors in a community-based
      population in Japan.
AB  - BACKGROUND: The association of obesity measures (ie, body mass index (BMI), waist
      circumference (WC) and waist-to hip ratio (WHR)) with metabolic risk factors in
      community-based populations has not been well studied. METHODS AND RESULTS: In
      the present study 759 men and 1,255 women aged between 30 and 79 years, without
      histories of stroke or coronary heart diseases, were dichotomized at the medians
      of BMI-WHR, WC-WHR and BMI-WC. The accumulation of 4 metabolic risk factors (risk
      _ sum) were examined: high blood pressure (> or =130/85 mmHg or on
      antihypertensive therapy); high triglycerides (> or =170 mg/dl); low high-density
      lipoprotein-cholesterol (<40 mg/dl); and impaired glucose tolerance (hemoglobin
      A1c > or =5.6% or on antidiabetic therapy). BMI and WC correlated well in both
      men (r=0.871) and women (r=0.874). All 3 obesity measures related with the
      metabolic risk factors. The area under the receiver-operating characteristic
      curve for BMI, WC and WHR to predict the risk _ sum > or =2 for men was 0.683,
      0.709, and 0.700, respectively, and 0.715, 0.739, and 0.746, respectively, for
      women. CONCLUSIONS: BMI may be used instead of WC if the latter is not available.
      When WC is measured, hip circumference also should be measured because the WHR
      may be the most valuable measure of obesity.

PMID- 17457009
TI  - Influence of cerebrovascular arteriosclerosis on cerebral oxygenation during
      exercise.
AB  - BACKGROUND: Although it is assumed that cerebral oxygenation during exercise is
      influenced by both cardiopulmonary function and cerebrovascular arteriosclerosis,
      the latter factor has not been fully clarified. In the present study the
      relationship between the degree of cerebrovascular arteriosclerosis and cerebral
      oxygenation during exercise was investigated. METHODS AND RESULTS: A total of 109
      patients (69 patients with coronary artery disease, 40 patients with hypertensive
      heart disease) (61.7+/-9.7 years) performed a symptom-limited exercise test with
      respiratory gas measurements (CPX). From the respiratory gas analysis, peak O(2)
      uptake (VO(2)), the slope of the increase in VO(2) to the increase in work rate
      (DeltaVO (2)/DeltaWR), and the slope of the increase in ventilation to the
      increase in CO(2) output (VE/VCO(2) slope) were calculated. Oxyhemoglobin
      (O(2)Hb) at the forehead was monitored using near-infrared spectroscopy. The
      brain ischemic score was counted based upon fluid-attenuated inversion recovery
      images of magnetic resonance imaging and expressed from 0 to 4. When compared
      with patients with a lower ischemic score (<2, n=67), those with a higher
      ischemic score (> or =2, n=42) had a lower increase in brain O(2)Hb during
      exercise (-1.08 +/-2.7 vs 0.77+/-4.1 micromol/L, p=0.011). Of brain ischemic
      score, left ventricular ejection fraction, peak VO(2), DeltaVO(2)/DeltaWR, and
      the VE/VCO(2) slope, DeltaVO(2)/ DeltaWR was found to be the sole independent
      index determining cerebral O(2)Hb during exercise. The CPX parameters were also
      significantly related to the degree of cerebrovascular arteriosclerosis.
      CONCLUSIONS: Although cerebral oxygenation during exercise is mainly related to
      cardiopulmonary function, the degree of cerebrovascular arteriosclerosis partly
      influences cerebral oxygenation in patients with risk factors for
      atherosclerosis.

PMID- 17457010
TI  - Novel rat model of ischemic cardiomyopathy induced by repetitive myocardial
      ischemia/reperfusion injury while conscious.
AB  - BACKGROUND: A rodent model of ischemic cardiomyopathy (ICM) induced by repetitive
      brief ischemia/reperfusion (I/R) injury while conscious has not been previously
      established. METHODS AND RESULTS: A newly developed coronary occluder was
      implanted in male Wistar rats. A repetitive I/R protocol (20 s, 2 min, followed
      by main 30 min--ischemia, every 48 h, for 4 weeks) was introduced while the
      animals were conscious. The I/R protocol did not induce transmural scar formation
      but induced (1) residual myocytes with scattered infiltration of fibrosis (Masson
      trichrome stain), (2) coronary hypoperfusion ((201)Tl-Cl autoradiogram), (3)
      reduced coronary microvascular volume fraction (microCT), and (4) gradually
      progressive left ventricular (LV) dilation (echocardiography). These parameters
      of ICM showed interindividual variation; however, the percent increase in LV
      diastolic area on day 3 was significantly correlated with LV dilation (r=0.91,
      p<0.0001), fibrosis (r=0.77, p=0.0034), and reduction in microvessels (r=0.67,
      p=0.040) at week 4. The LV dilatory response on day 3 also correlated with
      inducible nitric oxide synthase expression (immunohistochemistry, day 3) in the
      LV (r=0.92, p=0.028). CONCLUSIONS: A novel rat model of ICM induced by repetitive
      I/R while conscious showed interindividual variation in the severity of ICM in
      the advanced stage, but this was predictable non-invasively (by LV dilatory
      response) during the initial stage of repetitive I/R.

PMID- 17457011
TI  - Stanniocalcin 1 prevents cytosolic Ca2+ overload and cell hypercontracture in
      cardiomyocytes.
AB  - BACKGROUND: The aim of the present study was to examine whether stanniocalcin 1
      (STC1) affects cardiomyocytes under physiological or pathophysiological
      conditions. METHODS AND RESULTS: Using fresh isolated rat cardiomyocytes, the
      effects of STC1 on cell hypercontracture, cell shortening and Ca(2+) transients
      were measured after exposing the cells to ouabain. STC1 alone did not affect cell
      shortening or the Ca(2+) transient. Exposure to ouabain significantly increased
      the fraction of hypercontractured cells (40.5+/-1.4% vs 3.5+/-1.7% in the
      control, p<0.01). However, treatment with STC1 decreased the percentage of cell
      hypercontracture that was induced by ouabain, in a concentration-dependent manner
      (17.4+/-2.6% at 2.5 nmol/L STC1, p<0.01). Moreover, STC1 prevented the increase
      in diastolic intracellular Ca(2+) level that was induced by ouabain (-5.3+/-2.7%
      vs 7.9+/-3.7% induced by ouabain, p<0.05; -15.3+/-5.1% in the control) in the
      cardiomyocytes. CONCLUSIONS: STC1 prevented the increase in diastolic Ca(2+)
      overload and ouabain-induced cell hypercontracture, which suggests that STC1
      could effectively prevent cytosolic Ca(2+) overload and protect cardiomyocytes
      from pathophysiological conditions such as in the failing heart.

PMID- 17457012
TI  - Fibroblast growth factor (FGF)23 in patients with acromegaly.
AB  - Fibroblast growth factor (FGF)23 is a hormone that regulates serum phosphate and
      1,25-dihydroxyvitamin D levels. Hyperphosphatemia is sometimes observed in
      patients with acromegaly while the detailed mechanism of this abnormal phosphate
      metabolism remains to be elucidated. We have measured FGF23 levels in 18 patients
      before and after the surgery for acromegaly. Serum GH, IGF-I and phosphate
      significantly decreased after the surgery. In addition, FGF23 also reduced by the
      surgery. These results indicate that deficient action of FGF23 is not the cause
      of deranged phosphate metabolism in patients with acromegaly.

PMID- 17457013
TI  - Preferable effect of pravastatin compared to atorvastatin on beta cell function
      in Japanese early-state type 2 diabetes with hypercholesterolemia.
AB  - While a large numbers of clinical trials using various kinds of statins has been
      reported, a possible preventive effect on new onset of type 2 diabetes mellitus
      was shown only by the subanalysis of The West of Scotland Coronary Prevention
      Study (WOSCOPS) using pravastatin. The aim of this study was to investigate
      whether pravastatin has a preferable effect on glucose tolerance among statins.
      An open-label prospective cross-over trial was performed to compare the effect of
      pravastatin (10 mg/day) or atorvastatin (10 mg/day) in Japanese early-state type
      2 diabetes mellitus with hypercholesterolemia. The analyzed study subjects were
      treated with pravastatin (10 mg/day, n = 12) or atorvastatin (10 mg/day, n = 12)
      for 12 weeks. After a 4-week-washout period, the drugs were switched and
      treatment was continued for another 12 weeks. Oral glucose tolerance test (OGTT)
      was performed to evaluate several parameters including the appropriateness of
      beta cell function for the individual insulin sensitivity (disposition index:
      product of a validated secretion parameter and sensitivity) at the end of each
      therapy. HbA(1c) and 2 h-glucose levels during OGTT in the pravastatin treatment
      were significantly lower than atorvastatin treatment. Disposition index after
      pravastatin treatment was significantly higher than after atorvastatin treatment.
      In conclusion, our study suggests that pravastatin has a favorable effect on
      pancreatic beta cell function compared with atorvastatin.

PMID- 17457014
TI  - Diagnosis of a case of ectopic parathyroid adenoma on the early image of 99mTc
      MIBI scintigram.
AB  - We report the case of a 64-year-old woman who had a severe hypercalcemia. Serum
      calcium, intact parathyroid hormone (PTH), 1alpha, 25 (OH)(2 )vitamin D(3) levels
      were all elevated, and serum phosphorus level was decreased, which were all
      consistent with primary hyperparathyroidism (PHPT). (201)Tl/(99m)Tc subtraction
      scintigraphy failed to detect any abnormal accumulation in the neck and chest,
      while (99m)Tc-MIBI scintigraphy demonstrated the focal accumulation of increased
      radiotracer uptake in the mediastinum only on the early image, but not on the
      delayed image. Neck and chest computerized tomography scanning showed a small
      nodule at the retrosternal region, and a selective venous sampling study of the
      intact PTH suggested PTH production from the nodule. Together with the
      observation of the early image of (99m)Tc-MIBI scintigraphy, it was diagnosed
      that the patient had an ectopic parathyroid adenoma. Video-assisted thoracic
      surgery was performed. A 15-mm diameter mass, visualized by an intravenous
      infusion of methylene blue, was excited. The histopathology was consistent with
      the parathyroid adenoma. The adenoma was composed of mainly chief cells and
      rarely oxyphil cells. The absence of oxyphil cells would explain the lack of
      (99m)Tc-MIBI retention on late-phase imaging in our case. Even without uptake on
      the delayed image of (99m)Tc-MIBI scintigram, the early image was available for
      the localization of an ectopic parathyroid adenoma.

PMID- 17457015
TI  - A case of insulin-induced localized lobular panniculitis with evidence for the
      phagocytosis of insulin by histiocytes.
AB  - Insulin-induced localized lipoatrophy is a well-known localized side effect.
      Although an immune process has been suggested as its etiology, no definitive
      evidence has been reported to show that insulin is involved. Here, we report the
      first evidence for the phagocytosis of insulin by histiocytes as a very early
      stage of lipoatrophy, which was reproducible in two different lobular
      panniculitis tissues from a 71 year-old male patient. He had taken a subcutaneous
      insulin injection in his arms because of a sight disturbance. Since these
      subcutaneous tumors were likely due to inflammation by insulin, a biopsy sample
      was taken from the subcutaneous tumor of his right arm with his consent. The
      primary antibodies for insulin (1 : 200) and CD68 (1 : 50) were obtained from
      DAKO (guinea pig anti-insulin and mouse anti-human CD68). HE staining revealed
      the infiltration of mononuclear cells and histiocytes into the subcutaneous fat
      tissue, and some parts of this tissue had fibrosis with rich collagen fibers.
      These findings are consistent with a lobular panniculitis. Some histiocytes
      contained intracellular substances with a positive immunoreactivity to insulin.
      This activity was reduced when the anti-insulin antibody was preincubated with an
      excess amount of insulin antigen. The same substances were also positive to CD68.
      Thus, the phagocytosis of insulin by histiocytes appears to occur in this region.
      Therefore, the activation of subcutaneous macrophages by the complex of insulin
      and insulin antibodies may account for the initial autoimmune process.

PMID- 17457016
TI  - Fenofibrate increases high molecular weight adiponectin in subjects with
      hypertriglyceridemia.
AB  - Beneficial effects of peroxisome proliferator-activated receptor alpha (PPAR
      alpha) agonists have been reported in improving insulin sensitivity and raising
      serum total adiponectin. High molecular weight (HMW) adiponectin, which is
      secreted from adipocytes, and visfatin, which is also expressed in adipose
      tissue, is related to glucose metabolism. In view of the additive effects of PPAR
      alpha agonists on these adipocytokines and glucose metabolism, we investigated
      male hypertriglyceridemic subjects who were treated with fenofibrate. Eleven male
      subjects with hypertriglyceridemia were treated with fenofibrate and serum total
      cholesterol (T-cho), triglyceride, high-density lipoprotein cholesterol (HDL-C),
      low-density lipoprotein cholesterol (LDL-C), fasting glucose, fasting insulin,
      total and HMW adiponectin, and serum visfatin levels were determined before and 3
      months after treatment. Fenofibrate treatment significantly lowered T-cho,
      triglyceride, and LDL-C levels. There was a statistically significant increase of
      HDL-C. No differences in insulin sensitivity indices (G/I ratio and HOMA-IR) were
      observed between before and after treatment with fenofibrate. The treatment did
      not alter the levels of serum total adiponectin and visfatin in the
      hypertriglyceridemic patients, while serum HMW adiponectin increased
      significantly. This study demonstrates that fenofibrate increases serum HMW
      adiponectin levels, whereas visfatin is not regulated by fenofibrate in
      hypertriglyceridemic subjects. Further investigations are warranted to determine
      whether the elevation of HMW adiponectin caused by fenofibrate might improve
      insulin sensitivity.

PMID- 17457017
TI  - Head trauma in female professional wrestlers.
AB  - The clinical characteristics of head trauma were evaluated in 18 wrestlers
      belonging to a female professional wrestling organization, 13 regular members and
      five trainees aged 15-34 years. Medical examinations for head trauma were
      performed in all wrestlers, and wrestlers treated at our emergency outpatient
      department were clinically evaluated. In addition, the relationships of head
      trauma with duration of the wrestling career of 1-16 years (mean 8 years) in the
      regular members, and less than 1 year in the five trainees, and body mass index
      (BMI) of 21.0-32.0 in the 16 subjects, excluding two trainees, was evaluated.
      Chronic symptoms were noted in four of the 18 wrestlers with long wrestling
      careers (16 years in 1, 13 years in 1, and 5 years in 2). Three wrestlers with
      symptoms immediately after head trauma showed recurrent retrograde amnesia and
      had low BMI (21.6, 21.6, and 23.1). Five wrestlers were treated at our emergency
      outpatient clinic, three required hospitalization and two showed intracranial
      traumatic changes on computed tomography (acute subdural hematoma in 1 and
      diffuse brain swelling in 1). Head trauma in female professional wrestlers is
      associated with longer wrestling career and low BMI. Periodic medical
      examinations are recommended to monitor for signs of head trauma.

PMID- 17457018
TI  - Internal carotid artery bifurcation aneurysms: surgical experience.
AB  - Internal carotid artery (ICA) bifurcation aneurysms are relatively uncommon and
      frequently rupture at a younger age compared to other intracranial aneurysms. We
      have treated a total of 999 patients for intracranial aneurysms, of whom 89
      (8.9%) had ICA bifurcation aneurysms, and 42 of the 89 patients were 30 years of
      age or younger. The present study analyzed the clinical records of 70 patients
      with ICA bifurcation aneurysms treated from mid 1997 to mid 2003. Multiple
      aneurysms were present in 15 patients. Digital subtraction angiography films were
      studied in 55 patients to identify vasospasm and aneurysm projection. The
      aneurysm projected superiorly in most of these patients (37/55, 67.3%). We
      preferred to minimize frontal lobe retraction, so widely opened the sylvian
      fissure to approach the ICA bifurcation and aneurysm neck. Elective temporary
      clipping was employed before the final dissection and permanent clip application.
      Vasospasm was present in 24 (43.6%) of 55 patients. Forty-eight (68.6%) of the 70
      patients had good outcome, 14 (20%) had poor outcome, and eight (11.4%) died.
      Patients with ICA bifurcation aneurysms tend to bleed at a much younger age
      compared to those with other intracranial aneurysms. Wide opening of the sylvian
      fissure and elective temporary clipping of the ICA reduces the risk of
      intraoperative rupture and perforator injury. Mortality was mainly due to poor
      clinical grade and intraoperative premature aneurysm rupture.

PMID- 17457019
TI  - Ruptured aneurysm of the distal anterior cerebral artery: clinical features and
      surgical strategies.
AB  - Ruptured aneurysms of the distal anterior cerebral artery (ACA) are relatively
      rare and surgical management provides some unique technical challenges. This
      retrospective analysis of 20 patients with distal ACA aneurysms evaluated the
      clinical features and surgical strategies. The characteristic findings were small
      and common concurrent aneurysms, and frequent intracerebral hematoma (ICH).
      Aneurysms were divided by location on the genu (n = 13), infracallosal (n = 5),
      and supracallosal portions (n = 2). All patients except one underwent surgery via
      an interhemispheric route. Unilateral craniotomy was performed for aneurysms on
      the genu portions without massive ICH. Bilateral craniotomies were selected for
      aneurysm located on the infracallosal portion or combined with massive ICH. No
      intraoperative rupture was observed. Favorable outcomes were achieved in 15 of 20
      patients, and only one patient died. The preoperative Hunt and Kosnik grade was
      closely correlated with the outcome.

PMID- 17457020
TI  - Expression of WT1 protein and correlation with cellular proliferation in glial
      tumors.
AB  - The expression of Wilms' tumor gene WT1 protein was investigated
      immunohistochemically in 73 glial tumors, including 60 astrocytic tumors, eight
      oligodendroglial tumors, and five ependymal tumors. WT1 protein was detected in
      70 of the 73 glial tumors (95.9%) examined. Almost all glioblastomas, anaplastic
      astrocytomas, anaplastic ependymomas, and anaplastic oligodendrogliomas expressed
      high levels of WT1 protein. A significant (p < 0.001) correlation was found
      between WT1 protein expression and MIB-1 staining index. Histological examination
      found that WT1 protein was strongly expressed in the anaplastic portions and
      areas with perivascular proliferation and high cellularity, implying that WT1
      gene might be important in glial tumor cell proliferation. WT1 gene is
      overexpressed in various types of solid tumors and WT1 protein is a target
      antigen for cancer immunotherapy. This study indicates that many malignant glial
      tumors are good candidates for cancer immunotherapy targeting WT1 protein and
      that WT1 protein expression could be used as a proliferation marker in glial
      tumors.

PMID- 17457021
TI  - Intracerebral cavernous malformation induced by radiosurgery. Case report.
AB  - A 37-year-old man was treated for lung cancer by chemo-radiation therapy.
      Subsequently, magnetic resonance (MR) imaging identified a ring-enhanced lesion
      in the left temporal lobe. Gamma knife radiosurgery was performed under a
      diagnosis of brain metastasis. Nevertheless, MR imaging showed regrowth of the
      tumor 1 year later, so radiosurgery was repeated on the same lesion. Two years
      after the first radiosurgery, MR imaging revealed an irregularly enhanced lesion
      with increasing perifocal edema in the left temporal lobe. Emergency surgery was
      performed under a diagnosis of impending uncal herniation. The histological
      diagnosis was cavernous malformation. This case demonstrates that gamma knife
      radiosurgery can cause radiation-induced cavernous malformation.

PMID- 17457022
TI  - Frontal anaplastic oligodendroglioma showing multi-organ metastases after a long
      clinical course. Case report.
AB  - A 17-year-old woman presented with an anaplastic oligodendroglioma manifesting as
      generalized seizure. Neuroimaging studies revealed a right frontal tumor.
      Histological examinations of biopsy specimens revealed that the tumor was
      oligodendroglial in nature. Total resection was repeated four times, and
      malignant change was evident within the tissues. The final diagnosis was
      anaplastic oligodendroglioma. Despite irradiation, combination chemotherapy, and
      interstitial hyperthermia, the tumor grew rapidly but was confined to the cavity
      created by previous removal operations. She suffered bone pain in the last 3
      months of her life, when neuroimaging examinations disclosed multiple bone
      lesions. She died at the age of 29 years. At autopsy, generalized metastases from
      the tumor were identified at various sites, including the dura mater covering the
      frontal lobes and thoracic cord, cavernous sinus, tuberculum sellae, spleen,
      liver, pancreas, lungs, paratracheal lymph nodes, vertebral bodies, ribs,
      sternum, pelvis, dorsal root ganglia, and iliopsoas muscle. This rare case of
      cerebral anaplastic oligodendroglioma developed in adolescence, and rapid
      hematogenous spread of the glioma cells into the systemic organs occurred after a
      relatively long clinical course.

PMID- 17457023
TI  - Multiple cavernous angiomas of the cauda equina. Case report.
AB  - An 18-year-old male presented with multiple cavernous angiomas of the cauda
      equina manifesting as acute onset of severe low back pain radiating into the
      bilateral legs. Magnetic resonance imaging revealed a 20 mm by 15 mm nonenhanced,
      heterogeneous intensity intradural mass at the L-1 level, which had completely
      obliterated the spinal canal. After laminectomy at T12-L1 and dural incision, a
      20 mm dark-bluish, mulberry-like tumor was seen, displacing the cauda equina
      circumferentially. After total removal of this tumor, four more small tumors were
      found adhering to different nerve roots, which were not resected. Histological
      examination revealed cavernous angioma. Although the postoperative course was
      uneventful, close observation of the residual tumors is required.

PMID- 17457024
TI  - Atlantoaxial dislocation associated with a mass in the extradural craniovertebral
      junction unrelated to rheumatoid arthritis. Case report.
AB  - A 61-year-old woman without rheumatoid arthritis (RA) was admitted with
      atlantoaxial dislocation (AAD) and a retroodontoid mass at the craniovertebral
      junction manifesting as a 1-year history of numbness and mild weakness of the
      right upper extremity. Computed tomography and magnetic resonance (MR) imaging
      showed AAD and a mass at the craniovertebral junction. She had no past history of
      RA or trauma in the head and neck. She underwent surgery to obtain the
      histological diagnosis of the mass and to improve AAD-induced instability. The
      lesion was approached through the right transcondylar fossa approach with C-1
      laminectomy. Intraoperative pathological examination showed cicatrizing collagen
      fibers and no obvious tumor cells. After partial removal of the lesion, the AAD
      was fixed with the posterior approach. The symptoms subsided soon after surgery
      and the mass decreased on MR images taken 3 months after surgery. If a
      pseudotumor is suspected based on the preoperative radiological investigation in
      a non-RA patient with AAD and the symptoms are not progressive, stabilization can
      be expected to induce spontaneous regression without urgent direct excision of
      the mass.

PMID- 17457025
TI  - Delayed hemorrhage following microvascular decompression. Three case reports.
AB  - Postoperative hemorrhage is one of the most dangerous complications following
      microvascular decompression (MVD), and usually occurs within the first 24 hours
      after MVD operation, whereas delayed hemorrhage is extremely rare. The possible
      mechanisms of acute and delayed postoperative hemorrhage following MVD seem to be
      different. Three of 685 patients treated by MVD developed delayed hematoma more
      than 24 hours after surgery, including two cases at the operative site and one at
      a remote site. The possible causes of such delayed hemorrhage are discussed.
      Postoperative monitoring is extremely important after the MVD procedure. If any
      hemorrhage can be identified at the early stage, valuable time can be won for
      treatment and better outcome.

PMID- 17457026
TI  - Posterior C1-2 Fixation with cancellous screw and rod system for retro-odontoid
      pseudotumor associated with chronic atlantoaxial subluxation. Technical note.
AB  - Posterior C1-2 fixation with individual screw placement in C-1 and C-2 was
      performed in three patients presenting with progressive myelopathy caused by
      retro-odontoid pseudotumor associated with chronic atlantoaxial subluxation.
      Postoperatively, all patients demonstrated neurological recovery with gradually
      diminishing pseudotumor. Posterior C1-2 fixation with the cancellous screw and
      rod system is a safe and reliable method, and can be used to treat retro-odontoid
      pseudotumor associated with chronic atlantoaxial subluxation.

PMID- 17457027
TI  - Retrograde neuron tracing with microspheres reveals projection of CGRP
      immunolabeled vestibular afferent neurons to the vestibular efferent nucleus in
      the brainstem of rats.
AB  - OBJECTIVE: A new retrograde neuron-tracing technique with microspheres was used
      to explore the possible innervation of calcitonin gene-related peptide (CGRP)
      immunolabeled vestibular afferent neurons in the vestibular efferent
      immunolabeled nucleus in the brainstem. METHODS: 0.1 microl of 5%
      microfluorospheres was injected into the area of the vestibular efferent nucleus,
      which is located lateral to the genu of the facial nerve. CGRP
      immunohistochemistry was processed in serial sections of the brainstem at the
      facial nerve genu level. Double-labeled neurons with both CGRP immunoreactivity
      and microfluorospheres were examined with fluorescence and confocal laser
      microscopy. RESULTS: Three types of labeled neurons were observed: (1) neurons
      only retrogradely microfluorosphere-labeled that were mainly located in the
      medial vestibular nucleus, lateral vestibular nucleus, superior vestibular
      nucleus and parvicellular reticular nucleus on the ipsilateral side of the
      injection; (2) neurons that were both immunolabeled with CGRP and also
      retrogradedly labeled with microfluorospheres, indicating that they are CGRP
      cells projecting to the area of vestibular efferent nucleus, these cells were
      mainly distributed in the superior vestibular nucleus and dorsal vestibular
      nucleus, and (3) cells only immunolabeled for CGRP that were scattered
      extensively in the brainstem. CONCLUSION: The presented methodical contribution
      demonstrates the suitability of fluorescein-labeled microspheres for retrograde
      neuronal tracing. The vestibular nuclei contain numerous afferent neurons that
      send projections to the vestibular efferent nucleus, some of which are CGRP
      cells. This afferent innervation provides morphological evidence that the
      vestibular efferent neurons receive input from the vestibular afferent neurons
      including CGRP cells. These vestibular primary CGRP afferent neurons may have an
      influence on vestibular efferent neurons. CGRP acts as an important co
      transmitter or modulator in the afferent-mediated activity of vestibular efferent
      neurons, which in turn affect afferents in the vestibular end organs.

PMID- 17457028
TI  - Proteinuria as a therapeutic target in patients with chronic kidney disease.
AB  - Patients excreting large amounts of urinary protein, who are otherwise deemed to
      be optimally treated, should still be considered at high risk for renal disease
      progression. The observation that reductions in urinary protein excretion, in a
      graded fashion over a relatively short period of time, correlate with long-term
      preservation of renal function supports the idea of using urinary protein
      excretion as a guide to implementation of renoprotective therapies. The
      association between residual proteinuria and renal outcomes suggests that
      minimization of proteinuria is an important therapeutic goal in the management of
      proteinuric chronic kidney disease patients. This article reviews the evidence
      for using proteinuria as a target for the implementation of therapies shown to
      have renal protective effects.

PMID- 17457029
TI  - Metabolic correlates of brain reserve in dementia with Lewy bodies: an FDG PET
      study.
AB  - BACKGROUND: Studies suggest that brain reserve allows patients with more years of
      schooling to cope better with brain damage. Research has been mainly focussed on
      Alzheimer's disease and no studies exist on patients with dementia with Lewy
      bodies (DLB). The aim of this study was to provide evidence for brain reserve in
      DLB. METHODS: Twenty-one consecutive patients with DLB and 16 age-matched healthy
      controls were included. The participants underwent cerebral (18)F-FDG PET imaging
      at rest. A group comparison was conducted in SPM2 between the patient and control
      groups. A linear regression analysis with glucose metabolism as the dependent and
      years of schooling as the independent variable was performed. Age, gender and a
      total score of the Consortium to Establish a Registry for Alzheimer's Disease
      neuropsychological battery were included as covariates into the analysis.
      RESULTS: The patients showed a significant metabolic reduction in the frontal and
      posterior association cortices, the basal ganglia and the pulvinar of the
      thalami. Glucose metabolism and education showed an inverse relationship in an
      extensive cluster in the left temporo-parieto-occipital cortex. CONCLUSION:
      Similar findings were previously reported in Alzheimer's disease and are regarded
      as evidence for brain reserve. Therefore, we suggest that brain reserve is also
      present in DLB.

PMID- 17457030
TI  - Altered expression of COX-2 in subdivisions of the hippocampus during aging and
      in Alzheimer's disease: the Hisayama Study.
AB  - BACKGROUND: It has been reported that nonsteroidal anti-inflammatory drugs may
      delay the onset of Alzheimer's disease (AD). Since nonsteroidal anti-inflammatory
      drugs inhibit cyclooxygenase (COX), COX-2, an inducible form of COX, may be
      involved in the pathology of AD in association with the arachidonic acid cascade.
      In addition, it has been suggested that alterations in the balance of
      polyunsaturated fatty acids are associated with brain dysfunctions such as
      neurodegerative pathologies of the aging brain. METHOD: To explore COX-2
      expression in the hippocampus, we analyzed 45 consecutive autopsy subjects
      without dementia and 25 AD patients derived from the town of Hisayama, Japan.
      RESULTS: The neuronal expression of COX-2 in the CA3 subdivision of the
      hippocampus, subiculum, entorhinal cortex and transentorhinal cortex were
      consistently observed in both nondemented and AD brains, and COX-2
      immunoreactivity correlated with age in nondemented brains. In AD patients,
      neurons of CA1 exhibited increased COX-2 immunoreactivity which correlated with
      the severity of AD pathology. This correlation was not apparent in nondemented
      subjects. CONCLUSION: These results suggest that COX-2 expression may be
      differentially regulated among subdivisions of the hippocampus and that elevated
      COX-2 expression in the CA1 of AD brains may be associated with AD pathology and
      thus cognitive dysfunction.

PMID- 17457031
TI  - Sigma receptor type 1 gene variation in a group of Polish patients with
      Alzheimer's disease and mild cognitive impairment.
AB  - The sigma-1 receptor (SIGMAR1) is a subtype of a nonopioid sigma receptor family
      and is implicated in numerous functions connected with Alzheimer's disease (AD).
      Two common genetic variants were identified in SIGMAR1: GC-241 -240TT and Q2P
      (A61C). It was suggested that the TT-C haplotype is a protective factor for AD.
      We decided to investigate a putative link between the variants of SIGMAR1 and AD
      in a group of Polish patients with late-onset AD, in patients with mild cognitive
      impairment, and in a control group. We observed no significant differences for
      the SIGMAR1 allele, genotype, haplotype, and diplotype distributions between the
      studied groups. Multivariate logistic regression analysis showed no interaction
      between the APOE4 and SIGMAR1 polymorphisms. Further studies using data from
      different populations are required to elucidate the effect of SIGMAR1
      polymorphisms on AD.

PMID- 17457032
TI  - Prognostic significance of pre- and postoperative serum carcinoembryonic antigen
      levels in patients with colorectal cancer.
AB  - BACKGROUND: To evaluate the prognostic significance of pre- and postoperative
      serum carcinoembryonic antigen(CEA) levels in colorectal cancer (CRC) patients.
      METHODS: 425 CRC patients underwent curative resection at our institution. Their
      pre- and postoperative serum CEA level was classified into two groups according
      to concentration: normal CEA (<5.0 ng/ml) and abnormal CEA (> or =5.0 ng/ml).
      RESULTS: Of all patients, abnormal pre- and postoperative serum CEA levels were
      observed in 181 (42.6%) and 48 (11.3%) patients, respectively. Abnormal
      preoperative serum CEA level was significantly correlated with the tumor located
      in the colon, the depth of tumor invasion, the status of lymph node metastasis,
      UICC stage, and the presence of postoperative relapse (p < 0.05). Concurrently,
      an abnormal postoperative serum CEA level was also prominently related to the
      above corresponding parameters (p < 0.05), except for the tumor location.
      Patients with a failed conversion of abnormal preoperative value to normal
      postoperative concentration were found to have the worst overall survival rate.
      Abnormal pre- and postoperative serum CEA levels were single independent
      predictors for survival and postoperative relapse, respectively. CONCLUSIONS: The
      identification of abnormal pre- and postoperative serum CEA levels may be useful
      in the auxiliary cancer prognosis or postoperative surveillance of CRC patients.

PMID- 17457033
TI  - Nongenetic model of type 2 diabetes: a comparative study.
AB  - Seven-week-old male Sprague-Dawley (SD) rats were divided into six groups (LFC,
      LFD, HFC, HFD30, HFD40, HFD50) to determine whether animals receiving a low-fat
      (LF) diet plus nicotinamide-streptozotocin (NA-STZ) injection or animals
      receiving a high-fat (HF) diet plus STZ injection provide a better model of type
      2 diabetes. After 2 weeks of feeding, diabetes was induced by intraperitoneal
      injection of NA (230 mg/kg BW) and STZ (65 mg/kg BW) in LFD, and STZ 30, 40, 50
      mg/kg BW to HFD30, HFD40, HFD50 groups, respectively. Fasting blood glucose at 48
      72 h and nonfasting blood glucose at 1 week after STZ injection were >200 and
      >600 mg/dl, respectively, in HFD40 and HFD50 groups while no significant
      difference was observed among other groups. Serum insulin concentration was
      significantly (p < 0.05) decreased in LFD, HFC, HFD30, and HFD40 groups compared
      to LFC and HFD50 groups. One animal died and other animals of the HFD50 group
      were in a critical condition. Serum lipid and liver glycogen were increased in
      HFD groups compared to other groups. The results of this study suggest that the
      HF diet-fed, 40-mg/kg BW STZ-injected SD rat is better than the LF diet-fed NA
      STZ-injected rat as an animal model of human type 2 diabetes.

PMID- 17457034
TI  - Mitophagy: growing in intricacy.

PMID- 17457035
TI  - Ubiquitin trafficking to the lysosome: keeping the house tidy and getting rid of
      unwanted guests.
AB  - Bacterial killing by autophagic delivery to the lysosomal compartment has been
      shown for Mycobacteria, Streptococcus, Shigella, Legionella and Salmonella,
      indicating an important role for this conserved trafficking pathway for the
      control of intracellular bacterial pathogens.(1-5) In a recent study we found
      that solubilized lysosomes isolated from bone marrow-derived macrophages had
      potent antibacterial properties against M. tuberculosis and M. smegmatis that
      were associated with ubiquitin and ubiquitin-derived peptides. We propose that
      ubiquitinated proteins are delivered to the lysosomal compartment, where
      degradation by lysosomal proteinases generates ubiquitin-derived peptides with
      antimycobacterial properties. This surprising finding provokes a number of
      questions regarding the nature and trafficking of ubiquitin and ubiquitin
      modified proteins in mammalian cells. We discuss the possible role(s) that the
      multivesicular body (MVB), the late endosome and the autophagosome may play in
      trafficking of ubiquitinated proteins to the lysosome.

PMID- 17457036
TI  - AMP-activated protein kinase: a universal regulator of autophagy?
AB  - Autophagy is a lysosomal pathway involved in the turnover of cellular
      macromolecules and organelles. Starvation and various other stresses increase
      autophagic activity above the low basal levels observed in unstressed cells,
      where it is kept down by mammalian target of rapamycin complex 1 (mTORC1). In
      starved cells, LKB1 activates AMP-activated protein kinase (AMPK) that inhibits
      mTORC1 activity via a pathway involving tuberous sclerosis complex 1 and 2
      (TSC1/2) and its substrate Rheb. The present study suggests hat AMPK inhibits
      mTORC1 and autophagy also in nonstarved cells. Various Ca(2+) mobilizing agents
      (vitamin D compounds, thapsigargin, ATP and ionomycin) activate MPK via
      activation of Ca(2+)/calmodulin-dependent kinase kinase-beta (CaMKK-beta), and
      his pathway is required for Ca(2+)-induced autophagy. Thus, we propose that an
      increase in free cytosolic Ca(2+) ([Ca(2+)](c)) induces autophagy via the
      CaMKK/beta-AMPK-TSC1/2-Rheb-mTORC1 signaling pathway and that AMPK is a more
      general regulator of autophagy than previously expected.

PMID- 17457037
TI  - The heterotrimeric G protein G(i3) regulates hepatic autophagy downstream of the
      insulin receptor.
AB  - Compelling evidence suggests that the heterotrimeric G protein G(i3) specifically
      transmits the antiautophagic effects of insulin and amino acids in the liver.
      This points to a previously unrecognized cross talk between the insulin receptor
      tyrosine kinase and G(i3). Interestingly, G(i3) is localized not only to plasma
      membranes but also to membranes of the autophagosomal compartment. Furthermore,
      as part of insulin's or phenylalanine's actions to inhibit autophagy, G(i3) is
      redistributed away from autophagosomes. Therefore, endomembrane-associated rather
      than plasma membrane-localized G(i3) may serve as the target of insulin's
      endocrine and metabolic actions. We therefore propose that the function and
      regulation of organelle-associated heterotrimeric G proteins may be different
      from their roles at the plasma membrane where they act as signal transducers of
      seven-transmembrane receptors. Here, we discuss recent findings and propose a
      function for G(i3) in mTOR-dependent signaling pathways. We hypothesize that G(i)
      family members may have tissue-specific roles in the regulation of autophagy
      under different physiological and pathological conditions.

PMID- 17457038
TI  - Mitochondrial DNA deletions and chloramphenicol treatment stimulate the
      autophagic transcript ATG12.
AB  - Deletion mutations of mitochondrial DNA (mtDNA) accumulate somatically on a cell
      by-cell basis with age, resulting in decreased cell function in muscle and
      substantia nigra. In osteosarcoma cells deletions incapacitate mitochondria and
      induce the autophagic transcript ATG12, which is involved in an early step of the
      mammalian autophagy pathway. We discuss here which consequences of mtDNA
      deletions could induce ATG12, and provide two new pieces of data. Our previous
      studies demonstrated that mtDNA deletions decreased mitochondrial ATP production
      and proteasomal function, induced the AMPK transcript (likely as a consequence of
      bioenergetic depletion), and decreased the intracellular concentration of 20
      amino acids (possibly as a consequence of decreased proteasomal activity).
      Deletions eliminate essential tRNAs for mitochondrial protein synthesis, as well
      as essential components of mitochondrial multisubunit enzymes; therefore, the
      increased level of ATG12 could result from decreased bioenergetic function,
      increased oxidative damage, or decreased mitochondrial protein synthesis.
      However, the bioenergetic inhibitor rotenone does not induce ATG12. We show here
      that chloramphenicol, which inhibits mitochondrial protein synthesis, induces
      ATG12, and that mtDNA deletions result in an increased burden of oxidatively
      damaged protein. Thus, mtDNA deletions could induce ATG12 through a mechanism
      such as the following: deletions > mitochondrial protein synthesis inhibition or
      ROS > proteasome inhibition > amino acid depletion > ATG12.

PMID- 17457039
TI  - Hsp60 and Hspl0 as antitumor molecular agents.
AB  - The molecular chaperones Hsp60 and Hsp10 are, according to recent reports,
      involved in cancer development and progression. We, for instance, have found that
      their expression varies with distinctive patterns in different malignancies: they
      are overexpressed in colorectal, exocervical and prostate carcinogenesis, and
      colorectal cancer progression, but they are downregulated during bronchial
      carcinogenesis. There is also evidence showing that Hsp60 and Hsp10 can be used
      as therapeutic agents, for example in rheumatoid arthritis. In view of these
      findings we want now to call attention to the potential of Hsp60 and Hsp10 in
      cancer therapy.

PMID- 17457040
TI  - Silencing of heparanase by siRNA inhibits tumor metastasis and angiogenesis of
      human breast cancer in vitro and in vivo.
AB  - Expression of the heparanase gene is associated with invasive, angiogenic and
      metastatic potential of diverse malignant tumors and cell lines. Here we used RNA
      interference strategies to evaluate the role of human heparanase in breast
      malignancy and to explore the therapeutic potential of its specific targeting.
      The siRNA targeting human heparanase almost completely inhibited the expression
      of heparanase in human breast carcinoma MDA-MB-435 cells, whereas the mismatched
      siRNA showed no effect. Cells transfected with heparanase siRNA expressed
      significantly less heparanase and profoundly reduced invasion and adhesion in
      vitro. In MDA-MB-435 cell xenograft model, tumors treated with siRNA were less
      vascularized and less metastatic than those treated with saline and the
      mismatched controls. The association of reduced levels of heparanase and altered
      tumorigenic properties in cells with anti-heparanase siRNA indicates that
      heparanase is important in cancer progress and has potential use as a target for
      anticancer drug development.

PMID- 17457041
TI  - Phenoxodiol-Topotecan co-administration exhibit significant anti-tumor activity
      without major adverse side effects.
AB  - OBJECTIVE: We previously showed that Phenoxodiol is able to sensitize epithelial
      ovarian cancer cells to Paclitaxel, Carboplatin, Gemcitabine, and Docetaxel. The
      aim of this study was to determine the value of Phenoxodiol-Topotecan
      coadministration. METHODS: Nine epithelial ovarian cancer cell lines isolated
      from ascites or ovarian tissue were treated with increasing concentrations of
      Topotecan (5-500 ng/ml) with or without Phenoxodiol pretreatment (10 microg/ml)
      for 24 h and cell viability was measured using CellTiter 96 AQueous One Solution
      Cell Proliferation Assay. The effect of Phenoxodiol-Topotecan combination therapy
      in vivo was determined using the topotecan resistant A2780 mouse xenograft model.
      RESULTS: In vitro, pretreatment with Phenoxodiol lowers the topotecan IC50 from
      >500 ng/ml to 2.5-100 ng/ml in five out of nine cell lines tested. RESULTS from
      animal experiments confirmed the advantage of Phenoxodiol-Topotecan combination
      therapy over monotherapy controls. Median tumour kinetics from animals receiving
      Phenoxodiol-Topotecan in combination was significantly slower compared to those
      animals receiving the respective monotherapies. In addition, co-administration
      with Phenoxodiol reversed Topotecan-induced myelosuppression. CONCLUSION:
      Phenoxodiol-Topotecan combination therapy allows the administration of both
      agents at lower doses while retaining significant anti-tumor activity compared to
      monotherapy. These findings suggest that the Phenoxodiol-Topotecan combination
      may represent an alternative treatment modality for the management of ovarian
      cancer and justifies further investigation in the clinical setting.

PMID- 17457042
TI  - EGFR inhibition in glioblastoma cells induces G2/M arrest and is independent of
      p53.
AB  - Mutations involving the TP53 gene are frequently identified in up to 50% of all
      human tumors, including glioblastomas. Analysis of expression patterns of TP53 in
      glioblastomas shows that it is mainly mutated in secondary glioblastomas and is
      less common in primary GBMs. However, the prognostic significance of TP53 loss of
      function in astrocytomas has always been controversial. In contrast, EGFR/erbB2
      complexes have been implicated in the poor prognosis of several cancers,
      including glioblastomas. Our previous work showed that transforming phenotypes
      could be inhibited by interfering with active EGFR/erbB2 complex using mutant
      erbB2 proteins in wild-type p53 GBM cells. To assess the dependence of EGFR
      inhibited phenotype on p53, we used three mutant p53 glioblastoma cell lines in
      the present study and showed that mutant erbB2 can be exploited to inhibit EGFR
      mediated oncogenic transformation irrespective of p53 status. Ectopic expression
      of a mutant erbB2 receptor (T691S) in mutant p53 GBM cells resulted in slower
      growth rate than empty vector controls. T691S-expressing clones exhibited a more
      flattened and nontransformed morphology. Consistently, T691S inhibited
      transformation in soft agar assays and tumor formation in nude mice independent
      of p53 status. Biochemical analysis showed reduced Akt and GSK-3 alpha/beta, but
      not p42/44MAPK phosphorylation, in T691S-expressing cells, when compared to
      parental controls, suggesting the P13-K pathway may be more relevant than MAPK
      for glial cell transformation. Cell cycle analysis showed reduced cyclin D1 and
      CDK6 and increased phospho-Cdc-2 (Tyr15) and p15INK4B in erbB2-inhibited cells,
      suggesting that nonfunctional EGFR/erbB2 complexes exert their inhibitory effects
      at various stages of the cell cycle to block the progression of cells through
      G2/M via Akt/GSK-3/Cdc2 pathway. Collectively, these observations provide a basis
      for receptor-based therapies that disable erbB receptors and inhibit
      proliferative signals in erbB-expressing human cancers including glioblastomas,
      regardless of their TP53 status.

PMID- 17457043
TI  - High copy amplification of the Aurora-A gene is associated with chromosomal
      instability phenotype in human colorectal cancers.
AB  - Chromosomal instability (CIN) is a common but not universal feature of colorectal
      cancer (CRC); however, the molecular basis for CIN is controversial and poorly
      understood. There are many plausible mechanisms proposed for CIN, including
      disruption of G1/S and G2/M checkpoint regulation, and alterations in the spindle
      checkpoint genes. However, mutations in individual growth regulatory genes are
      not commonly observed in CRC. Therefore, a more comprehensive analysis of the
      genes involved in each cell cycle checkpoint regulatory pathway might be required
      to evaluate a possible role for involvement in CIN. We investigated the presence
      of high copy amplification of the cyclin E, Aurora-A, Skp2 genes, mutation of
      ubiquitin ligase CDC4, and promoter methylation of Mad2L1, as well as the
      expression of the gene products in a panel of 11 human CRC cell lines as well as
      48 human CRC specimens. In the cell lines with CIN, we found amplification of the
      Aurora-A, cyclin E and Skp2 genes, and a mutation in the CDC4 gene, all of which
      resulted in altered expression of the cognate proteins. In the human CRC tissues,
      amplification of Aurora-A was frequent (29%), while alterations were rarely
      observed in cyclin E, Skp2 or CDC4. Aurora-A amplification was strongly
      associated with a high fractional allelic loss score (p = 0.0001), but not with
      microsatellite instability, nor with the promoter methylation phenotype in these
      tumors. Our data confirm involvement in the CDC4-cyclin E pathway of the
      development of the CIN phenotype in human CRC, and find that amplification of the
      Aurora-A is a common target for disruption of this pathway.

PMID- 17457044
TI  - A phase II study of ixabepilone (BMS-247550) in metastatic renal-cell carcinoma.
AB  - INTRODUCTION: Ixabepilone (BMS-247550) is a semi-synthetic analog of epothilone B
      that has been characterized as a microtubule stabilizing agent with a mechanism
      of action distinct from taxanes. Suggestion of activity in renal cell carcinoma
      (RCC) has been seen in early clinical studies. METHODS: Eligible patients had
      metastatic RCC as well as ECOG performance status 0-2 and normal organ function.
      Patients received ixabepilone at a dose of 40 mg/m2 intravenously over three
      hours every 21 days. There was no restriction on RCC histology or prior treatment
      type, but prior treatment with tubule inhibitors was not allowed. The primary
      endpoint was RECIST defined response and radiographic evaluations were performed
      every three cycles. Toxicity evaluations utilized CTCAE v3.0 and were performed
      every cycle. Using a Simon two-stage optimal design with alpha = 0.1, beta = 0.1,
      a null hypothesized response rate of 0.05 and an alternative response rate of
      0.2, an initial 12 patients were to be accrued with full accrual of 37 patients
      if at least one response were observed. RESULTS: A median of five cycles were
      administered. No objective responses were observed in the first 12 evaluable
      patients, and six patients showed stable disease for more than 18 weeks on
      therapy. Median time to progression among those with objective progression was
      nine weeks. One patient experienced grade 4 anemia and lymphopenia. Grade 3
      adverse events included lymphopenia, neutropenia, leukopenia, diarrhea, and
      infection. Common grade 2 toxicities included alopecia, fatigue and anemia.
      CONCLUSION: Ixabepilone administered at a dose of 40 mg/m2 every 21 days should
      not be advanced for further study in metastatic RCC. Given previous results,
      however, other dosing schedules may be worthy of further investigation.

PMID- 17457045
TI  - Pheophorbide a, an active component in Scutellaria barbata, reverses P
      glycoprotein-mediated multidrug resistance on a human hepatoma cell line R-HepG2.
AB  - Scutellaria barbata, a Traditional Chinese Medicine native in southern China, has
      been widely used for treating liver diseases. In this study, the anti
      proliferative effect of Pheophorbide a (Pa), an active component from S. barbata,
      was examined on a multi-drug resistant (MDR) human hepatoma cell line R-HepG2.
      Our study showed that Pa could significantly inhibit the growth of R-HepG2 cells
      with an IC50 value at 25.0 microM after 48 hours treatment. When compared with
      the parental HepG2 cells, Pa showed weak resistance to R-HepG2. Efflux of Pa out
      of R-HepG2 cells was not observed as its cellular uptake level showed no
      significant difference comparing with HepG2 cells. Interestingly, significant
      reduction of P-glycoprotein expression on Pa-treated R-HepG2 cells was found at
      both transcriptional and translational levels, leading to reduction of P
      glycoprotein activity. In addition, mechanistic study elucidated that Pa induced
      cell cycle arrest at G2/M phase and inhibited the expressions of G2/M phase cell
      cycle regulatory proteins, cyclin-A1 and cdc2 in a dose-dependent manner.

PMID- 17457046
TI  - Velafermin improves gastrointestinal mucositis following irinotecan treatment in
      tumor-bearing DA rats.
AB  - Mucositis is a common, costly and unpleasant side effect of cancer chemotherapy
      and radiotherapy. Velafermin (FGF-20) has shown the potential to reduce these
      side effects. Irinotecan is a chemotherapeutic agent which is commonly used in
      solid tumors, and causes GI mucositis manifested by severe diarrhea. Therefore
      the primary aim of this study was to investigate whether velafermin reduces the
      GI mucositis induced by irinotecan. The secondary aim was to test varying
      schedules of administration of velafermin. Groups of tumor-bearing DA rats (6 per
      group) were treated with varying doses (4, 8 or 16 mg/kg) of velafermin
      intraperitoneally either prior to, prior to and during, or after chemotherapy
      treatment. Rats received a single dose of 200 mg/kg irinotecan intraperitoneally.
      Rats were monitored closely for the incidence and severity of diarrhea and
      mortality before being killed 192 h following treatment. Mortality, diarrhea and
      histopathology were assessed throughout the gastrointestinal tract. Severe or
      moderate diarrhea occurred in approximately 40% of rats treated with irinotecan
      alone. This was associated with a 50% mortality rate 96 h following chemotherapy.
      Velafermin administered at 16 mg/kg prior to irinotecan improved gastrointestinal
      mucositis as measured by reduced diarrhea and mortality following irinotecan
      chemotherapy in the DA rat. Rats that received velafermin prior to, or prior to
      and during irinotecan treatment did develop severe or moderate diarrhea, however
      it occurred later, in fewer rats and was not associated with mortality. Other
      dosing regimens were not as effective. This has important implications for the
      use of velafermin in GI mucositis in humans, and should be further studied.

PMID- 17457047
TI  - ErbB3 expression and dimerization with EGFR influence pancreatic cancer cell
      sensitivity to erlotinib.
AB  - Abnormal expression and signaling of ErbB receptors has been implicated in
      multiple epithelial malignancies, including pancreatic cancer. Erlotinib, an
      epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been
      recently approved for pancreatic cancer treatment, but there are no reliable
      predictors of patient response. Expression of additional ErbB receptors seems to
      influence tumor response to EGFR-targeted therapy. We analyzed the influence of
      ErbB3 expression on pancreatic cancer cell response to erlotinib treatment.
      Proliferation assays of five human pancreatic cancer cell lines were performed
      following treatment with erlotinib. Expression and phosphorylation profiles of
      ErbB receptors and downstream adaptor protein (Akt, ERK1/2, STAT3, mTOR) were
      evaluated following stimulation with EGF or neuregulin-beta. The formation of
      EGFR homodimers and EGFR-ErbB3 heterodimers, necessary to enable ErbB3 downstream
      signaling, was demonstrated by chemical cross-linking assays. The effects of RNA
      inhibition of ErbB3 on sensitivity to erlotinib treatment were evaluated in AsPC
      1 pancreatic cancer cells. Erlotinib inhibited Akt phosphorylation and
      proliferation of all the ErbB3-expressing cell lines but did not affect mTOR
      activation. Cross-linking studies confirmed the presence of EGFR-ErbB3
      heterodimers in pancreatic cancer cells. Only the ErbB3-deficient MIA PaCa-2
      cells displayed persistent Akt activation and ongoing proliferation in spite of
      erlotinib treatment. siRNA-mediated inhibition of ErbB3 expression in AsPC-1
      cells resulted in acquired resistance to erlotinib treatment. Pancreatic cancer
      cells which lack ErbB3 do not display activation of the ErbB3-PI3K-Akt cascade
      induced by EGFR/ErbB3 heterodimers and become less critically dependent on EGFR
      signaling and therefore resistant to erlotinib. Pancreatic cancer expression of
      ErbB3 may be useful for EGFR-targeted therapy patient selection.

PMID- 17457048
TI  - IGFBP-3 regulates esophageal tumor growth through IGF-dependent and independent
      mechanisms.
AB  - Insulin-like growth factor binding protein (IGFBP)-3 exerts either proapoptotic
      or growth stimulatory effects depending upon the cellular context. IGFBP-3 is
      overexpressed frequently in esophageal cancer. Yet, the role of IGFBP-3 in
      esophageal tumor biology remains elusive. To delineate the functional
      consequences of IGFBP-3 overexpression, we stably transduced Ha-Ras(V12)
      transformed human esophageal cells with either wild-type or mutant IGFBP-3, the
      latter incapable of binding Insulin-like growth factor (IGFs) as a result of
      substitution of amino-terminal Ile56, Leu80, and Leu81 residues with Glycine
      residues. Wild-type, but not mutant, IGFBP-3 prevented IGF-1 from activating the
      IGF-1 receptor and AKT, and suppressed anchorage-independent cell growth. When
      xenografted in nude mice, in vivo bioluminescence imaging demonstrated that wild
      type, but not mutant IGFBP-3, abrogated tumor formation by the Ras-transformed
      cells with concurrent induction of apoptosis, implying a prosurvival effect of
      IGF in cancer cell adaptation to the microenvironment. Moreover, there was more
      aggressive tumor growth by mutant IGFBP-3 overexpressing cells than control cell
      tumors, without detectable caspase-3 cleavage in tumor tissues, indicating an IGF
      independent growth stimulatory effect of mutant IGFBP-3. In aggregate, these data
      suggest that IGFBP-3 contributes to esophageal tumor development and progression
      through IGF-dependent and independent mechanisms.

PMID- 17457049
TI  - p53: guardian of the genome and policeman of the oncogenes.
AB  - The process of malignant transformation universally entails genetic damage and
      oncogenic signaling, two stresses that are signaled to p53 through different
      genetic pathways. Based on this, it is possible to distinguish two jobs for p53:
      "guardian of the genome" that consists in sensing and reacting to DNA damage
      through the ATM/ATR and Chk1/Chk2 kinases, and "policeman of the oncogenes" that,
      correspondingly, consists in responding to oncogenic signaling through the p53
      stabilizing protein ARF. Contrary to expectation, recent genetic evidence in mice
      indicates that the response of p53 to DNA damage has little or no impact on
      cancer protection. In contrast, ARF-dependent activation of p53 is critical for
      p53-mediated tumor suppression. Here, we discuss the mechanistic implications of
      these observations and their relevance for cancer therapy.

PMID- 17457050
TI  - The molecular biology of mammalian SIRT proteins: SIRT2 in cell cycle regulation.
AB  - Sir2, an NAD+-dependent protein deacetylase, extends the lifespan in diverse
      species from yeast to flies. Mammals have seven homologs of Sir2, SIRT1-7, which
      affect aging and metabolism and which are potential targets for pharmacologic
      intervention. We identified SIRT2, which preferentially deacetylates tubulin and
      histone H4, as a downregulated protein in gliomas due to its epigenetic
      aberration. We herein discuss the role of SIRT2 in the mitotic checkpoint
      function and show that it may be as a potential target of anti-cancer drugs.

PMID- 17457051
TI  - Methylation of human microRNA genes in normal and neoplastic cells.
AB  - MicroRNAs (miRNAs) are small RNA molecules that control gene expression by
      inhibition of protein translation or degradation of cognate target mRNAs.
      Eventhough strict Even though strict developmental and tissue-specific regulation
      appears to be critical for miRNA function, very little is known about the
      mechanisms governing miRNA gene expression. Several recent studies have shown
      that miRNA genes can regulated DNA methylation and other epigenetic mechanisms.
      The observation of altered miRNA gene methylation patterns in human cancers also
      suggested that miRNA gene methylation is functional relevant for tumorigenesis.
      We have now performed a comprehensive analysis of miRNA genes and found that
      about half of these genes are associated with CpG islands and thus represent
      candidate targets of the DNA methylation machinery An expanded analysis of
      several miRNA-associated CpG islands in five cell lines indicated that miRNA gene
      methylation is detectable at high frequencies, both in normal and malignant
      cells. Possible explanations for this phenomenon include the specific structure
      of miRNA genes and/or their requirement for strict expression regulation.

PMID- 17457052
TI  - Stem cell chromatin patterns: an instructive mechanism for DNA hypermethylation?
AB  - Epigenetic gene silencing, and associated promoter CpG island DNA
      hypermethylation, is an alternative mechanism to mutations by which tumor
      suppressor genes may be inactivated within a cancer cell. These epigenetic
      changes are prevalent in all types of cancer, and their appearance may precede
      genetic changes in premalignant cells and foster the accumulation of additional
      genetic and epigenetic hits. These epigenetically modified genes constitute
      important categories of tumor suppressor genes including cell cycle regulators,
      pro-differentiation factors, and anti-apoptotic genes, and many of these genes
      are known to play a role in normal development. While the silencing of these
      genes may play an essential role in tumor initiation or progression, the
      mechanisms underlying the specific targeting of these genes for DNA
      hypermethylation remains to be determined. The large numbers of epigenetically
      silenced genes that may be present in any given tumor, and the clustering of
      silenced genes within single cell pathways, begs the question of whether gene
      silencing is a series of random events resulting in an enhanced survival of a
      premalignant clone, or whether silencing is the result of a directed, instructive
      program for silencing initiation reflective of the cells of origin for tumors. In
      this regard, the current review stresses the latter hypothesis and the important
      possibility that the program is linked, at least for silencing of some cancer
      genes, to the epigenetic control of stem/precursor cell gene expression patterns.

PMID- 17457053
TI  - Lineage-specific transcription factors in multipotent hematopoietic progenitors:
      a little bit goes a long way.
AB  - Basal expression of lineage-specific transcription factors (TFs) in multipotent
      hematopoietic progenitor cells (HPCs) plays a pivotal role in normal
      hematopoiesis. Indeed, the interplay between lineage-specific TFs and chromatin
      modifying or remodeling complexes allows chromatin modifications at specific
      hematopoietic loci and promotes transcriptionally prone conformations. During
      hematopoiesis, the expression of various lineage-specific genes can be preceded
      by their potentiation i.e., by chromatin activation, in progenitor cells. Gene
      potentiation appears to counterbalance epigenetic silencing of lineage-specific
      genes in early progenitors, while maintaining an accessible chromatin
      conformation in the lineage pathway selected. Herein, we discuss the impact of
      lineage-specific TFs on gene potentiation and priming in normal hematopoiesis,
      and emphasize the complementary role of locus control region (LCR) or LCR-like
      structures and promoter regions in gene-specific potentiation events.

PMID- 17457054
TI  - Apigenin-induced cell cycle arrest is mediated by modulation of MAPK, PI3K-Akt,
      and loss of cyclin D1 associated retinoblastoma dephosphorylation in human
      prostate cancer cells.
AB  - Apigenin, a dietary plant-flavonoid has shown anti-proliferative and anticancer
      properties, however the molecular basis of this effect remains to be elucidated.
      We studied the molecular events of apigenin action in human prostate cancer
      cells. Treatment of LNCaP and PC-3 cells with apigenin causes G0-G1 phase arrest,
      decrease in total Rb protein and its phosphorylation at Ser780 and Ser807/811 in
      dose- and time-dependent fashion. Apigenin treatment caused increased
      phosphorylation of ERK1/2 and JNK1/2 and this sustained activation resulted in
      decreased ELK-1 phosphorylation and c-FOS expression thereby inhibiting cell
      survival. Use of kinase inhibitors induced ERK1/2 phosphorylation, albeit at
      different levels, and did not contribute to cell cycle arrest in comparison to
      apigenin treatment. Despite activation of MAPK pathway, apigenin caused a
      significant decrease in cyclin D1 expression that occurred simultaneously with
      the loss of Rb phosphorylation and inhibition of cell cycle progression. The
      reduced expression of cyclin D1 protein correlated with decrease in expression
      and phosphorylation of p38 and PI3K-Akt, which are regulators of cyclin D1
      protein. Interestingly, apigenin caused a marked reduction in cyclin D1, D2 and E
      and their regulatory partners CDK 2, 4 and 6, operative in G0-G1 phase of the
      cell cycle. This was accompanied by a loss of RNA polymerase II phosphorylation,
      suggesting the effectiveness of apigenin in inhibiting transcription of these
      proteins. This study provides an insight into the molecular mechanism of apigenin
      in modulating various tyrosine kinases and perturbs cell cycle progression,
      suggesting its future development and use as anticancer agent in humans.

PMID- 17457055
TI  - Plasticity of mammalian myotubes upon stimulation with a thrombin-activated serum
      factor.
AB  - Salamanders display unique regeneration abilities among adult vertebrates. An
      intriguing feature of salamander regeneration is the dedifferentiation of cells,
      such as myofibers and myotubes at the injury site, a process that involves cell
      cycle reentry from the differentiated state. A thrombin-activated serum factor
      that is distinct from conventional growth factors is known to cause S-phase
      reentry in salamander myotubes. While mammalian myotubes do not reenter S-phase
      upon serum stimulation, an upregulation of some immediate early genes such as jun
      and fos has been observed. Until now, it was unknown whether this transcriptional
      response was stimulated by conventional growth factors or by the thrombin
      activated serum factor. By measuring transcriptional activity in individually
      purified C2C12 mouse myotubes using quantitative reverse transcription polymerase
      chain reactions, we show that a set of immediate early genes are activated in
      response to the thrombin-activated serum factor in a distinct manner from the
      growth factors PDGF, FGF and EGF. A partially purified fraction of the thrombin
      activated serum factor elicited stronger upregulation of a broader set of genes
      compared to individual growth factors and additionally caused downregulation of
      E2F6. Despite this robust transcriptional response in mammalian myotubes, we did
      not detect a large-scale change in histone H3K9 di-methylation or S-phase, a
      feature that characterizes salamander serum-stimulated myotubes. Our results
      indicate that mammalian myotubes have retained responsiveness to the thrombin
      activated serum factor, but full reentry into S-phase is prevented by factors
      downstream of the immediate early genes.

PMID- 17457056
TI  - A Fhit-ing role in the DNA damage checkpoint response.
AB  - The FHIT gene encompasses the most active common fragile site of the human genome
      and is thus exquisitely sensitive to intragenic alterations by DNA damaging
      agents, alterations that can lead to FHIT allele loss very early in the
      preneoplastic phase of cancer development, before or coincident with activation
      of the DNA damage checkpoint. Fhit protein expression is lost or reduced in many
      preneoplastic lesions and in >50% of cancers, Fhit knockout mice are highly
      susceptible to carcinogen induction of tumors and Fhit replacement in these mice
      by gene therapy induces apoptosis and significantly reduces tumor burden. But
      learning how Fhit induces apoptosis and suppresses tumors has been a challenge
      because interacting proteins, effectors of Fhit signals, have not been
      discovered. Nevertheless, the study of Fhit deficient mouse and human tissue
      derived and cancer-derived cells in vitro has led to several important
      conclusions: repair protein-deficient cancers are more likely to be Fhit
      deficient; Fhit-deficient cells show enhanced resistance to UVC, mitomycin C,
      camptothecin and ionizing radiation-induced cell killing, possibly due to strong
      activation of the ATR pathway following DNA damage; Fhit-deficient cells show
      higher efficiency of homologous recombination repair, a double-strand break
      repair pathway in mammalian cells; Fhit protein indirectly affects S-phase
      checkpoint and DNA repair. Finally, results of a recent study have suggested that
      the DNA damage-susceptible FRA3B/FHIT chromosome fragile region, paradoxically,
      encodes a protein, Fhit, that is necessary for protecting cells from accumulation
      of DNA damage, through modulation of checkpoint proteins Hus1 and phosphoChk1.
      Thus, inactivation of Fhit contributes to accumulation of abnormal checkpoint
      phenotypes in cancer development. It will be very important to determine
      mechanisms employed by Fhit in modulating checkpoint pathways, and to define
      consequences of Fhit loss in specific preneoplastic and neoplastic tissues, to
      provide rationales for effective replacement or reactivation of endogenous Fhit
      pathways in novel therapeutic or preventive approaches.

PMID- 17457057
TI  - Phosphorylation by aurora-B negatively regulates survivin function during
      mitosis.
AB  - Survivin operates in a complex with aurora B kinase and is phosphorylated by it
      on threonine 117 in vitro. Here we ask whether phosphorylation of survivin by
      aurora B kinase regulates its function during mitosis in vivo. Using a phospho
      specific antibody we first establish that survivin is phosphorylated at T117
      during mitosis and is present at the midbody during cytokinesis. Next we use two
      independent RNAi complementation approaches to investigate threonine 117 mutants
      in survivin depleted cells. Our data suggest that while non-phosphorylatable
      survivin, survivin(T117A), can substitute for the wild type protein, a
      phosphomimic, survivin(T117E) cannot restore viability, nor can it complement
      chromosome congression and spindle checkpoint defects that arise due to depletion
      of endogenous survivin. Fluorescence imaging and fluorescence recovery after
      photobleaching analysis suggest that the phosphomimic has reduced affinity for
      centromeres compared with the non-phosphorylatable form. We conclude that
      survivin is phosphorylated at T117 during mitosis, and once phosphorylated,
      dephosphorylation is crucial for chromosome congression and progression into
      anaphase.

PMID- 17457058
TI  - CDK2 and FOXO1: a fork in the road for cell fate decisions.
AB  - It has been well established that cyclin-dependent kinases (CDKs) including CDK2
      and CDK1 play an essential role in mediating cell-cycle arrest, DNA repair and
      apoptosis in cells with damaged genomes. Following DNA damage, the function of
      CDKs is inhibited, and therefore cells are arrested at the G(1), S or G(2)/M
      phase of the cell-division cycle. It is believed that DNA damage-induced cell
      cycle arrest is important, because it allows cells to either repair the damage
      and survive or commit to apoptotic cell death. However, the molecular bases for
      the two cell fate options are not fully understood. Recently, we provided
      evidence that CDK2 interacts with and phosphorylates the forkhead transcription
      factor FOXO1. Importantly, activated CDK2 inhibits the pro-apoptotic function of
      FOXO1. However, in the presence of high levels of double-strand breaks (DSBs) the
      CDK2-mediated inhibition of FOXO1 is abrogated due to the ablation of CDK2
      activity, and therefore the anti-apoptotic function of FOXO1 is restored. Thus,
      CDK2 silencing-dependent activation of FOXO1 represents a new mechanism that
      links DNA strand breakage to cell death.

PMID- 17457059
TI  - ATM activation and DNA damage response.
AB  - Well before the gene (ATM) mutated in the human genetic disorder ataxia
      telangiectasia (A-T) was described it was evident from the clinical, molecular
      and cellular phenotype of A-T that this gene would play a central role in the DNA
      damage response. Mutation of ATM causes defective cell cycle checkpoint
      activation,a reduced capacity for repair of DNA double strand breaks and abnormal
      apoptosis, all of which contribute to the major features of A-T including genome
      instability, increased cancer risk and neurodegeneration. While the exact
      mechanism of activation remains unknown, it is clear that the Mre11 complex plays
      an important role both in the recruitment of ATM to the sites of DNA damage and
      in the efficient activation of ATM. Although ATM responds to agents that produce
      double strand breaks in DNA, other stimuli are also capable of ATM activation.
      The description of autophosphorylation on S1981 of ATM and the ensuing transition
      from an inactive dimer to an active monomer represents a major milestone in our
      understanding of the activation process. However, it is now evident that more
      than one autophosphorylation event is required and not surprisingly this process
      is also attenuated by phosphatases and other modifications such as acetylation
      are also implicated. This is further complicated by a recent report that
      autophosphorylation at S1987 (the mouse site corresponding to S1981) is
      dispensable for Atm activation in an Atm mutant mouse model. Use of cell extracts
      and in vitro approaches in the reconstruction of activation complexes have shed
      further light on what it takes to activate ATM. The aim here is to examine the
      evidence for the involvement of these various steps in ATM activation and attempt
      to put together a comprehensive picture of the overall process and its
      significance to DNA damage signaling.

PMID- 17457061
TI  - Clinical academies: innovative school-health services partnerships to deliver
      clinical education.
AB  - During the past five years (2001-2006), the University of Bristol Medical School
      has developed and implemented a new model for delivering clinical education: the
      clinical academy. The principal features of the model are (1) having both in
      Bristol and out-of-Bristol campuses for clinical education, (2) innovative
      partnerships with local health care providers, (3) local leadership of
      educational delivery, and (4) the recruitment and training of new cadres of
      clinical teachers. The seven clinical academies consist of two academies based in
      traditional acute-care teaching hospitals in the city of Bristol and five
      academies in the surrounding counties. The same Bristol curriculum is delivered
      in every clinical academy by locally recruited hospital specialists and family
      physicians. Each academy is led by an academy medical dean, who has local
      responsibility for program delivery, quality assurance, academic and personal
      support for students, and finances on behalf of the university. Medical students
      rotate between clinical academies every half academic year, alternately based in
      and outside of Bristol. They learn clinical medicine and develop clinical
      competence as apprentice members of a local multiprofessional learning community.
      The medical school now has enough high-quality clinical placements to accommodate
      increasing numbers of medical students whilst keeping a "human-scale" educational
      environment. Clinical academies are thus the key components of a decentralized
      system of curriculum delivery; they differ in concept and purpose from the new
      academies of medical educators in the United States that offer a centralized
      focus for the educational mission.

PMID- 17457062
TI  - The current status of medical genetics instruction in US and Canadian medical
      schools.
AB  - PURPOSE: Relatively little is known about how medical genetics is being taught in
      the undergraduate medical curriculum and whether educators concur regarding
      topical priority. This study sought to document the current state of medical
      genetics education in U.S. and Canadian accredited medical schools. METHOD: In
      August 2004, surveys were sent from the Indiana University School of Medicine to
      149 U.S. and Canadian medical genetics course directors or curricular deans.
      Returned surveys were collected through June 2005. Participants were asked about
      material covered, number of contact hours, year in which the course was offered,
      and what department sponsored the course. Data were collated according to
      instructional method and course content. RESULTS: The response rate was 75.2%.
      Most respondents (77%) taught medical genetics in the first year of medical
      school; only half (47%) reported that medical genetics was incorporated into the
      third and fourth years. About two thirds of respondents (62%) devoted 20 to 40
      hours to medical genetics instruction, which was largely concerned with general
      concepts (86%) rather than practical application (11%). Forty-six percent of
      respondents reported teaching a stand-alone course versus 54% who integrated
      medical genetics into another course. Topics most commonly taught were cancer
      genetics (94.2%), multifactorial inheritance (91.3%), Mendelian disorders
      (90.3%), clinical cytogenetics (89.3%), and patterns of inheritance (87.4%).
      CONCLUSIONS: The findings provide important baseline data relative to guidelines
      recently established by the Association of American Medical Colleges. Ultimately,
      improved genetics curricula will help train physicians who are knowledgeable and
      comfortable discussing and answering questions about genetics with their
      patients.

PMID- 17457063
TI  - Virtual patient simulation at US and Canadian medical schools.
AB  - PURPOSE: "Virtual patients" are computer-based simulations designed to complement
      clinical training. These applications possess numerous educational benefits but
      are costly to develop. Few medical schools can afford to create them. The purpose
      of this inventory was to gather information regarding in-house virtual patient
      development at U.S. and Canadian medical schools to promote the sharing of
      existing cases and future collaboration. METHOD: From February to September 2005,
      the authors contacted 142 U.S. and Canadian medical schools and requested that
      they report on virtual patient simulation activities at their respective
      institutions. The inventory elicited information regarding the pedagogic and
      technical characteristics of each virtual patient application. The schools were
      also asked to report on their willingness to share virtual patients. RESULTS:
      Twenty-six out of 108 responding schools reported that they were producing
      virtual patients. Twelve schools provided additional data on 103 cases and 111
      virtual patients. The vast majority of virtual patients were media rich and were
      associated with significant production costs and time. The reported virtual
      patient cases tended to focus on primary care disciplines and did not as a whole
      exhibit racial or ethnic diversity. Funding sources, production costs, and
      production duration influenced the extent of schools' willingness to share.
      CONCLUSIONS: Broader access to and cooperative development of these resources
      would allow medical schools to enhance their clinical curricula. Virtual patient
      development should include basic science objectives for more integrative
      learning, simulate the consequences of clinical decision making, and include
      additional cases in cultural competency. Together, these efforts can enhance
      medical education despite external constraints on clinical training.

PMID- 17457065
TI  - Musculoskeletal medicine: an assessment of the attitudes and knowledge of medical
      students at Harvard Medical School.
AB  - PURPOSE: To assess medical students' knowledge and clinical confidence in
      musculoskeletal medicine as well as their attitudes toward the education they
      receive in this specialty. METHOD: A cross-sectional survey of students in all
      four years of Harvard Medical School was conducted during the 2005-2006 academic
      year. Participants were asked to fill out a 30-question survey and a nationally
      validated basic competency exam in musculoskeletal medicine. RESULTS: The
      response rate was 74% (449/608). Medical students rated musculoskeletal education
      to be of major importance (3.8/5) but rated the amount of curriculum time spent
      on musculoskeletal medicine as poor (2.1/5). Third-year students felt a low to
      adequate level of confidence in performing a musculoskeletal physical examination
      (2.7/5) and failed to demonstrate cognitive mastery in musculoskeletal medicine
      (passing rate on competency exam: 7%), whereas fourth-year students reported a
      similar level of confidence (2.7/5) and exhibited a higher passing rate (26%).
      Increasing exposure to the subject by taking clinical electives resulted in
      greater clinical confidence and enhanced performance on the exam (P < .001).
      Students' feedback suggested that musculoskeletal education can be better
      integrated into the preclinical curriculum, more time should be spent in the
      field, and more focus should be placed on common clinical conditions.
      CONCLUSIONS: These findings, which are consistent with those from other schools,
      suggest that medical students do not feel adequately prepared in musculoskeletal
      medicine and lack both clinical confidence and cognitive mastery in the field.
      Implementing a four-year integrated musculoskeletal curriculum is one way that
      medical schools can address this concern.

PMID- 17457066
TI  - Medical training in school-based health centers: a collaboration among five
      medical schools.
AB  - School-based health centers (SBHCs) have tremendous untapped potential as models
      for learning about systems-based care of vulnerable children. SBHCs aim to
      provide comprehensive, community-based primary health care to primary and
      secondary schoolchildren who might not otherwise have ready access to that care.
      The staffing at SBHCs is multidisciplinary, including various combinations of
      nurse practitioners, physicians, dentists, nutritionists, and mental health
      providers. Although this unique environment provides obvious advantages to
      children and their families, medical students and residents receive little or no
      preparation for this type of practice. To address these deficiencies in medical
      education, five downstate New York state medical schools, funded by the New York
      State Department of Health, collaborated to define, develop, implement, and
      evaluate curricula that expose health professions students and residents to
      SBHCs. The schools identified core competencies and developed a comprehensive
      training model for the project, including clinical experiences, didactic
      sessions, and community service opportunities, and they developed goals,
      objectives, and learning materials for each competency for all types and levels
      of learners. Each school has implemented a wide range of learning activities
      based on the competencies. In this paper, the authors describe the development of
      the collaboration and illustrate the process undertaken to implement new
      curricula, including considerations made to address institutional needs,
      curricula development, and incorporation into existing curricula. In addition,
      they discuss the lessons learned from conducting this collaborative effort among
      medical schools, with the goal of providing guidance to establish effective cross
      disciplinary curricula that address newly defined competencies.

PMID- 17457068
TI  - Continuous quality improvement and community-based faculty development through an
      innovative site visit program at one institution.
AB  - This article describes and evaluates a unique site-visit process for community
      based teaching sites. A continuous quality-improvement program was developed by
      the undergraduate program in the Department of Family and Community Medicine at
      the University of Toronto Faculty of Medicine to facilitate and document both
      self- and peer-assessment. A pilot program was launched in 2000, and, after some
      adjustments based on initial feedback, the program in its current form was
      implemented in 2002. This program provides individualized support mechanisms to
      address the faculty development needs and infrastructure requirements of
      community-based, mostly volunteer, teachers. It also trains participating
      reviewers to provide individualized faculty development at the point of teaching.
      During their training, reviewers receive a toolkit consisting of suggestions for
      initial contact with teachers, guidelines for peer assessments, previously
      completed previsit teacher surveys, reviewer checklists, postvisit feedback
      forms, sample thank-you letters, and a faculty development reference resource
      list. A two-year evaluation of the program demonstrated that faculty and reviewer
      participants perceived it to be comprehensive, consistent, informative, and an
      acceptable method of reviewing existing and prospective community-based teaching
      sites. This program should be transferable to other institutions that engage in
      community-based teaching.

PMID- 17457069
TI  - Integrating gross anatomy into a clinical oncology curriculum: the oncoanatomy
      course at Duke University School of Medicine.
AB  - The amount of time devoted to teaching gross anatomy to medical students is
      declining. This topic remains critically important for some medical students,
      especially those seeking training in anatomy-laden specialties. The authors
      describe a course currently offered in the department of radiation oncology in
      the Duke University School of Medicine, developed in 2005, that expands anatomy
      education into the medical school clinical years. The aim of the course is to
      help reinforce anatomy knowledge in the clinical context of radiation oncology
      priorities and concerns, as well as to provide direct visualization and palpation
      of human cadavers, thus enabling the understanding of complex three-dimensional
      and anatomic principles. The audience for this course consists of medical
      students rotating through and the residents and clinical faculty in the
      department of radiation oncology. Anatomists and radiation oncology residents
      together present monthly didactic lectures, clinical case presentations, and
      cadaver-based demonstrations about the relationships between a tumor's anatomic
      location and its symptoms, patterns of spread, and treatment considerations.
      Anonymous surveys were distributed to course participants to assess the three
      components of the course. Survey results indicate that the participants found the
      anatomy lectures, clinical case presentations, and dissection presentations all
      to be interesting, relevant, and of high quality. This course is therefore
      favored by students, residents, and faculty as a way to supplement gross anatomy
      education during training for a specialty in which anatomy knowledge is
      essential.

PMID- 17457070
TI  - Too many cooks spoil the broth.

PMID- 17457071
TI  - A unique, innovative, and clinically oriented approach to anatomy education.
AB  - The establishment of The Cleveland Clinic Lerner College of Medicine of Case
      Western Reserve University, whose first class entered in 2004, provided a unique
      opportunity to design an anatomy program that, from all indications, is
      effective, time efficient, and clinically relevant in the context of a
      nonlecture, problem-based, organ-systems-oriented curriculum. Through
      consultation with surgery colleagues, the case-directed anatomy program was
      developed. This approach, meeting one day a week for 1 hour 50 minutes for 30
      weeks, uses clinical cases to introduce anatomical information that is reinforced
      using prosected cadavers and imaging. The format of the approach involves three
      steps: (1) students preview a clinical case with clinical questions and learning
      objectives, (2) students acquire basic knowledge using textbooks and self
      directed learning modules, and (3) students reinforce their basic knowledge in
      weekly case-directed anatomy sessions, which involve an interactive discussion of
      the clinical case followed by a laboratory. In the laboratory, students rotate
      around stations viewing prosected cadavers and imaging. Learning anatomy does not
      stop after the first year, because the program is longitudinal. During the second
      year, students review anatomy in each organ-system course using the first-year
      format. Also, second-year students can assist the fellows or residents prepare
      the prosections for first-year students and for their review of anatomy in the
      second year. This provides students with a dissection experience. During third
      year clinical rotations, anatomy knowledge is reinforced, and several surgery
      anatomy electives are available during the final year. In this way, anatomy is
      learned and reinforced throughout the medical school curriculum.

PMID- 17457072
TI  - Viewpoint: leaving the "empty glass" of problem-based learning behind: new
      assumptions and a revised model for case study in preclinical medical education.
AB  - The popularity of problem-based learning (PBL) reflects medical educators'
      recognition that case study can enhance the preclinical medical school
      curriculum. However, the PBL method itself has features, particularly its
      reliance on small-group work with tutor-facilitators, that are expensive to
      implement and that limit the potential educational value of case study. The
      author systematically analyzes specific aspects of the PBL methodology and
      concludes that the PBL approach misuses the faculty, tends to compromise the
      authenticity of cases, and results in an unnecessarily varied and impoverished
      educational experience for students. Approaches to case study with different
      assumptions need to be devised. A model is proposed that shifts the goal of case
      study from development of problem-solving skills to development of ideas that
      allow meaningful engagement in sophisticated discussions of medicine. In this
      model, the method shifts from self-directed learning to independent study guided
      by the expertise of the faculty. One possible approach to case study based on
      this model is briefly described. It consists of reading published cases from the
      medical literature, with analysis and discussion of the cases led by faculty
      experts in large-group format. The approach immerses students in an authentic,
      state-of-the-art discussion of medicine and is easily incorporated into any
      curriculum structure at limited cost. The author argues that, contrary to the
      claims of proponents, the glass is "mostly empty" for PBL and that we can
      generate the higher-level discussion that case study merits only by moving away
      from PBL's extraneous assumptions.

PMID- 17457073
TI  - A faculty development program to train tutors to be discussion leaders rather
      than facilitators.
AB  - PURPOSE: During 2003, 2004, and 2005, the role of 70 tutors was changed from that
      of facilitator to discussion leader, in a preclinical PBL learning course,
      Gastrointestinal Pathophysiology, by use of three key business school teaching
      strategies: questions, summaries, and schematics. The purpose of this study was
      to learn what difference this new approach made. METHOD: During each of the three
      study years, 171 (2003), 167 (2004), and 170 (2005) students were given Likert
      scale attitudinal questionnaires to rate whether their tutors encouraged student
      direction of the tutorials and whether the summaries and closure schematics
      benefited their learning. Students' overall course evaluations and mean USMLE
      scores were quantitatively analyzed, pre- and postintervention. A variety of
      statistical tests were used to assess the statistical significance of means at
      the confidence level of .05. RESULTS: In the third year of the program, student
      ratings indicated that their tutors were significantly better at encouraging
      student direction of the tutorials than in the first year (P < .05). The students
      reported that the tutorial made a more important contribution to their learning
      (P < .05), and the course objectives were better stated (P = .038) and better met
      (P = .007). Overall satisfaction with the course also improved significantly (P =
      .006). Part I gastrointestinal system mean scores of the USMLE showed a
      statistically significant increase in 2005 compared with 2001 or 2002.
      CONCLUSIONS: The tutor as a discussion leader who questions, summarizes, and uses
      schematics to illustrate concepts had a significant and positive impact on
      learning in tutorials, achieving course objectives, improving overall course
      satisfaction, and increasing a standardized national exam's mean score.

PMID- 17457074
TI  - The portfolio approach to competency-based assessment at the Cleveland Clinic
      Lerner College of Medicine.
AB  - Despite the rapid expansion of interest in competency-based assessment, few
      descriptions of assessment systems specifically designed for a competency-based
      curriculum have been reported. The purpose of this article is to describe the
      design of a portfolio approach to a comprehensive, competency-based assessment
      system that is fully integrated with the curriculum to foster an educational
      environment focused on learning. The educational design goal of the Cleveland
      Clinic Lerner College of Medicine of Case Western Reserve University was to
      create an integrated educational program-curriculum and instructional methods,
      student assessment processes, and learning environment-to prepare medical
      students for success in careers as physician investigators. The first class in
      the five-year program matriculated in 2004. To graduate, a student must
      demonstrate mastery of nine competencies: research, medical knowledge,
      communication, professionalism, clinical skills, clinical reasoning, health care
      systems, personal development, and reflective practice. The portfolio provides a
      tool for collecting and managing multiple types of assessment evidence from
      multiple contexts and sources within the curriculum to document competence and
      promote reflective practice skills. This article describes how the portfolio was
      developed to provide both formative and summative assessment of student
      achievement in relation to the program's nine competencies.

PMID- 17457075
TI  - Peer reviewing e-learning: opportunities, challenges, and solutions.
AB  - Peer review is the foundation of academic publication and a necessary step in the
      scrutiny of any scholarly work. Simply defined, peer review is the attentive,
      unbiased assessment of any scholarly work that is submitted for formal scrutiny.
      Although medical school faculty increasingly use technology in clinical teaching,
      e-learning materials are often not subjected to a rigorous peer review process.
      The authors contrast peer review of e-learning materials with that of print
      materials, describe peer review issues regarding e-learning materials, propose
      approaches to address the challenges of peer review of e-learning materials, and
      outline directions for refinement of the e-learning peer review process. At its
      core, the peer review of e-learning materials should not differ substantially
      from that of traditional manuscripts. However, e-learning introduces new demands
      that impel reviewers to consider aspects that are unique to educational
      technology, including pedagogy, format, usability, navigation, interactivity,
      delivery, ease of updating, distribution, and access. Four approaches are offered
      to ease the burden and improve the quality of e-learning peer review: develop
      peer review training, embrace multidisciplinary peer review, develop guidelines,
      and provide incentives and compensation. The authors conclude with suggestions
      about peer review research.

PMID- 17457076
TI  - Medical students' perceptions of emerging learning communities at one medical
      school.
AB  - PURPOSE: In 1999, the University of Iowa Roy J. and Lucille A. Carver College of
      Medicine (UICCOM) established a student management model consisting of four
      student-style learning communities (LCs), each comprising one quarter of the
      students from each class, with the goal of fostering student connection,
      excellence, learning, leadership, and service. The authors present results of a
      prospective evaluation of medical students' perceptions of emerging LCs and their
      impact on medical student life at UICCOM. METHOD: A two-page questionnaire,
      administered in 1999 and again in 2003 to all second-through fourth-year and
      MD/PhD students, assessed connections among students from different years of
      study, students' participation in activities, anticipated/perceived benefits of
      LCs, concerns about LCs, and the impact of LCs on students' perceptions of the
      learning environment. Questions were open ended or Likert scaled; statistical
      analyses were descriptive, parametric, and nonparametric. RESULTS: Comparison of
      results between 1999 and 2003 demonstrated increased connections between students
      and participation in LC activities, positive perceptions of the overall learning
      environment, increased access to faculty and staff, and increased involvement in
      leadership and service activities. Student concerns included continued obstacles
      to involvement in LCs for third- and fourth-year students. CONCLUSIONS: This
      prospective evaluation demonstrates that LCs can contribute to more positive
      perceptions of the learning environment and increased interaction between
      students throughout medical school. LCs seem to increase student leadership
      development and engagement in the broader community. Further investigation is
      needed to determine how these potential benefits of LCs can be maximized and made
      more accessible to all students.

PMID- 17457078
TI  - The mentored clinical casebook project at Harvard Medical School.
AB  - An excellent physician must be aware of the countless issues that affect each
      patient's health. Many medical education programs expose students to a broad
      spectrum of disparate knowledge and hope they will integrate all the pieces into
      a coherent whole. The authors describe an explicit approach to integration used
      at Harvard Medical School since 2003 that aims to enhance students' learning in
      medical school and throughout their medical careers: the Mentored Clinical
      Casebook Project (MCCP). The MCCP is constructed on the premise that such
      integration does not occur suddenly but, rather, is an unending process. A first
      year student is assigned to one clinician and follows one patient for one year.
      The student is expected to spend as much time with the patient as possible, in
      both clinical and nonclinical settings, seek help from the clinician, and consult
      other experts and sources to develop a complete picture of the patient's life.
      The student must produce a casebook that includes, but is not limited to, the
      patient's history; basic science, clinical, socioeconomic, and cultural issues;
      and self-reflection. The MCCP is intended to allow students to develop a deeper
      and more diverse understanding of what comprises a patient's health care life, to
      discern the patient as a person and the person as a patient. This educational
      project has been popular with students since its inception, providing them with a
      personal framework from which to address the needs of future patients and
      introducing them to how much they will continue to learn from their patients.

PMID- 17457079
TI  - University of South Florida College of Medicine (Tampa, Florida).

PMID- 17457080
TI  - Medicine and the arts. Winter Count 1973: Geese, They Flew Over in a Storm
      [excerpt] by Barry Lopez. Commentary.

PMID- 17457082
TI  - The role of adipokines in relation to HIV lipodystrophy.

PMID- 17457083
TI  - Testing antiretroviral drug efficacy in conventional mice infected with chimeric
      HIV-1.
AB  - OBJECTIVE: We previously described chimeric HIV-1, EcoHIV, which can infect mouse
      cells in culture and cause spreading infection in conventional immunocompetant
      mice. We have now applied this system as a model for preclinical evaluation of
      anti-retroviral drugs. DESIGN AND METHODS: We used chimeric virus EcoHIV/NDK
      constructed on the backbone of subtype D NDK. EcoHIV/NDK expression in mice was
      characterized 5-10 days after infection by testing viral DNA, RNA, and protein
      burdens in spleen and macrophages by real-time PCR (QPCR), RT-PCR, and p24 ELISA.
      For antiviral evaluation, groups of 5-7 mice were pretreated with 2',3'
      dideoxycytidine (ddC), abacavir, or vehicle; mice were then infected with
      EcoHIV/NDK, treatment maintained for additional 48 h, and tested for viral DNA
      and RNA burdens in spleens and macrophages by QPCR. RESULTS: EcoHIV/NDK infected
      mice reproducibly showed viral burdens of up to 1.4 x 10 viral DNA copies and 200
      pg p24 per 10 spleen cells and expressed spliced Vif RNA and mature p24 in
      macrophages 5-10 days after infection. Treatment of mice with 60 or 300 mg
      ddC/kg/day blocked EcoHIV/NDK infection in a dose-dependent manner with
      significantly lower viral DNA and RNA burdens at both drug doses (P < 0.001) in
      the spleens of infected mice. Abacavir tested at 100 mg/kg/day caused 96%
      inhibition of viral DNA synthesis in spleen and it almost completely abolished
      viral spliced RNA synthesis in spleens and macrophages. CONCLUSIONS: The system
      of chimeric HIV-1 infection of mice permits rapid, statistically powerful, and
      inexpensive evaluation of antiretroviral drugs in vivo.

PMID- 17457084
TI  - Gatekeeper role of 14-3-3tau protein in HIV-1 gp120-mediated apoptosis of human
      endothelial cells by inactivation of Bad.
AB  - OBJECTIVE: HIV-1-associated dementia (HAD) is a major neurological complication
      often observed in the advanced stages of AIDS. We have reported that 14-3-3
      proteins in cerebrospinal fluid, reflecting neuronal cell destruction, is a real
      time marker of HAD progression. This study was designed to examine the role of 14
      3-3 proteins in HAD. DESIGN: An in-vitro human umbilical vein endothelial cells
      (HUVEC) model of gp120 protein-induced apoptosis to study the protective role of
      14-3-3 in HIV-1 gp120/CXCR4-mediated cell death. METHODS: The alpha-chemokine
      receptor-mediated cell death by HIV-1 envelope protein, gp120, the critical event
      that causes neuron loss and endothelial cell injury, was evaluated in HUVEC
      undergoing gp120-induced apoptosis through the CXCR4 receptor. We studied the
      effects of siRNA for each 14-3-3 isoform on the death of HUVEC treated with CXCR4
      preferring gp120 (IIIB). RESULTS: Gp120 increased the expression of 14-3-3tau in
      HUVEC. The binding of Gp120 to CXCR4 induced apoptosis of HUVEC through decreased
      binding of 14-3-3tau to the pro-apoptotic molecule, Bad. Treatment of the cells
      with dsRNA against 14-3-3tau enhanced the gp120-mediated dephosphorylation of Bad
      and its association with Bcl-XL in mitochondria, accelerating the gp120-induced
      apoptosis, whereas suppression of Bad by RNAi rescued the cells from apoptosis
      triggered by gp120. CONCLUSIONS: The specific up-regulation of 14-3-3tau in HUVEC
      negatively regulated gp120/CXCR4-mediated cell death by protecting Bad
      dephosphorylation.

PMID- 17457085
TI  - Increased carotid intima media thickness and cardiac biomarkers in HIV infected
      children.
AB  - OBJECTIVES: To assess carotid intima media thickness (IMT) and cardiac biomarkers
      in HIV infected children on antiretroviral therapy (ART). METHODS: This was a
      single site, cross sectional, controlled observational study. We assessed carotid
      IMT, homocysteine, high-sensitivity C-reactive protein and myeloperoxidase levels
      in HIV infected children on stable ART for >or= 6 months. Carotid IMT was
      reported as internal carotid artery (ICA) and common carotid artery (CCA)
      thickness; left and right sides were measured separately. Groups were compared
      using appropriate two-sample tests. RESULTS: Of the 62 subjects enrolled, 31 were
      HIV positive (50%), 66% were female, and 69% were African-American. Median CD4%
      was 32% and 26 patients (84%) had HIV-1 RNA< 400 copies/ml. Sixteen patients had
      been taking protease inhibitors for a median duration of 27 months. None had
      hypertension or smoked. HIV infected children had higher HOMA-IR, waist-to-hip
      ratio, cholesterol, triglycerides, myeloperoxidase and lower homocysteine levels.
      Left and right CCA IMT, and left and right ICA IMT were significantly higher in
      the HIV infected group. Significant predictors of carotid IMT measurements in
      uninfected controls were body mass index and homocysteine, but only the duration
      of ARV therapy was predictive of IMT in the HIV infected group. CONCLUSION:
      Higher levels of carotid IMT and some cardiac markers were found in ART treated
      HIV infected children when compared to matched uninfected controls. These results
      suggest that HIV infected children receiving ART may be at increased risk of
      cardiovascular disease.

PMID- 17457086
TI  - In utero nucleoside reverse transcriptase inhibitor exposure and signs of
      possible mitochondrial dysfunction in HIV-uninfected children.
AB  - BACKGROUND: There is equivocal evidence of in utero nucleoside reverse
      transcriptase inhibitor (NRTI) exposure and the occurrence of mitochondrial
      dysfunction (MD) in HIV-uninfected children born of HIV-infected women. METHODS:
      The primary analysis included 1037 HIV-uninfected children born in 1991-2002 and
      enrolled in Pediatric AIDS Clinical Trials Group protocols 219/219C. Possible
      cases with unexplained signs of MD according to the Enquete Perinatale Francaise
      criteria were identified through retrospective review. Associations between
      overall in utero NRTI exposure, and trimester of first in utero NRTI exposure and
      possible MD were estimated with exact logistic regression. RESULTS: Cases (n =
      20) were significantly more likely to be male and to be born in earlier years
      than non-cases (n = 1017). There was no association between overall in utero NRTI
      exposure and MD. In unadjusted models there were higher odds of first in utero
      exposure in the third trimester to lamivudine (3TC) [odds ratio (OR), 3.76 versus
      3TC unexposed; 95% confidence interval (CI), 1.09-11.78] and to zidovudine (ZDV)
      and 3TC in combination (ZDV/3TC) (OR, 3.29 vs. ZDV/3TC unexposed; 95% CI, 0.96
      10.25) among cases than noncases. When adjusted for year of birth the odds of
      first exposure in the third trimester to 3TC (OR, 10.57; 95% CI, 1.93-75.61) and
      ZDV/3TC (OR, 9.84; 95% CI, 1.77-71.68) were significantly higher among cases than
      non-cases. Incomplete data precluded control of possible confounding by maternal
      viral load and psychoactive drug use. CONCLUSIONS: Our study suggests that first
      exposure to 3TC or ZDV/3TC in the third trimester may be associated with the
      occurrence of possible MD. Further studies that rigorously assess MD and better
      control confounding are needed.

PMID- 17457087
TI  - Treatment initiation with zidovudine-containing potent antiretroviral therapy
      impairs CD4 cell count recovery but not clinical efficacy.
AB  - OBJECTIVE: Zidovudine-containing antiretroviral therapy has been associated with
      a lower rise in absolute CD4 cell counts in several randomized trials. We
      examined the predictive factors for this phenomenon and assessed its impact on
      clinical progression during treatment in a large patient cohort. DESIGN: An
      analysis of data from the Swiss HIV Cohort Study. METHODS: All 2177 treatment
      naive adults who began potent antiretroviral therapy (ART) between September 1995
      and September 2004 were included. Exclusion criteria were previous ART and
      treatment duration of less than 3 months. Follow-up was censored in the case of a
      treatment switch or stop. RESULTS: A total of 1312 patients initiated zidovudine
      containing ART and 865 started ART without zidovudine. Except for slightly higher
      absolute CD4 cell counts in the zidovudine group, prognostic characteristics at
      baseline and viral suppression during treatment did not differ. During an
      observation time of 2343 and 1486 patient-years, the CD4 cell count increased by
      a median of 221 versus 286 cells/microl at 2 years and 290 versus 379
      cells/microl at 4 years in the zidovudine versus no zidovudine group; however,
      the rise in the percentage of CD4 cells was similar in both groups. The
      zidovudine group had a significantly slower rise in total lymphocytes and
      haemoglobin. In multivariable Cox models, the hazard for new HIV-associated
      clinical events was not affected by zidovudine-containing ART. CONCLUSION: Over 4
      years, zidovudine led to a smaller increase in absolute, but not percentage, CD4
      cell counts. The effect can be explained as a slower rise in total lymphocytes
      and has no impact on clinical efficacy.

PMID- 17457088
TI  - Lamivudine/abacavir maintains virological superiority over zidovudine/lamivudine
      and zidovudine/abacavir beyond 5 years in children.
AB  - OBJECTIVE: To describe the long-term efficacy over 5 years of regimens including
      combinations of abacavir, lamivudine and/or zidovudine in previously untreated
      children in the PENTA 5 trial. DESIGN: PENTA 5 was a 48-week randomised
      controlled trial comparing three dual nucleoside reverse transcriptase inhibitor
      (NRTI) combinations as part of first triple antiretroviral therapy (ART).
      METHODS: 128 ART-naive children were randomised to zidovudine?lamivudine (n =
      36), zidovudine?abacavir (45) or lamivudine?abacavir (47). Asymptomatic children
      (n = 55) were also randomised to nelfinavir or placebo; all other children
      received open-label nelfinavir. Analyses are intent-to-treat and adjusted for
      minor baseline imbalances and receipt of nelfinavir/placebo. RESULTS: Median
      follow-up was 5.8 years. By 5 years, 17 (47%), 28 (64%) and 18 (39%) children had
      changed their randomised NRTIs in the zidovudine?lamivudine, zidovudine?abacavir
      and lamivudine?abacavir groups respectively, but 18%, 50% and 50% of these
      changes were either early single drug substitutions for toxicity or switches with
      viral suppression (HIV-1 RNA < 400 copies/ml; e.g. to simplify regimen delivery).
      At 5 years, 55%/32% zidovudine?lamivudine, 50%/25% zidovudine?abacavir and
      79%/63% lamivudine?abacavir had HIV-1 RNA < 400/< 50 copies/ml respectively (p =
      0.03/p = 0.003). Mean increase in height-for-age 0.42, 0.68, 1.05 (p = 0.02);
      weight-for-age 0.03, 0.13, 0.75 (p = 0.02). Reverse transcriptase resistance
      mutations emerging on therapy differed between the groups: zidovudine?lamivudine
      (M41L, D67N, K70R, M184V, L210W, T215Y); zidovudine?abacavir (M41L, D67N, K70R,
      L210W, T215F/Y, K219Q); lamivudine?abacavir (K65R, L74V, Y115F, M184V).
      CONCLUSIONS: Five year data demonstrate that lamivudine?abacavir is more
      effective in terms of HIV-1 RNA suppression and growth changes, with lower rates
      of switching with detectable HIV-1 RNA than zidovudine?lamivudine or
      zidovudine?abacavir, and should be preferred as first-line NRTI backbone.

PMID- 17457089
TI  - Early clinical and immune response to NNRTI-based antiretroviral therapy among
      women with prior exposure to single-dose nevirapine.
AB  - OBJECTIVE: To determine whether prior exposure to single-dose nevirapine (NVP)
      for prevention of mother-to-child HIV transmission (PMTCT) is associated with
      attenuated CD4 cell response, death, or clinical treatment failure in women
      starting antiretroviral therapy (ART) containing non-nucleoside reverse
      transcriptase inhibitors (NNRTI). METHODS: Open cohort evaluation of outcomes for
      women in program sites across Zambia. HIV treatment was provided according to
      Zambian/World Health Organization guidelines. RESULTS: Peripartum NVP exposure
      status was known for 6740 women initiating NNRTI-containing ART, of whom 751
      (11%) reported prior use of NVP for PMTCT. There was no significant difference in
      mean CD4 cell change between those exposed or unexposed to NVP at 6 (+202 versus
      +182 cells/microl; P = 0.20) or 12 (+201 versus +211 cells/microl; P = 0.60)
      months. Multivariable analyses showed no significant differences in mortality
      [adjusted hazard ratio (HR), 1.2; 95% confidence interval (CI), 0.8-1.8] or
      clinical treatment failure (adjusted HR, 1.1; 95% CI, 0.8-1.5). Comparison of
      recent NVP exposure with remote exposure suggested a less favorable CD4 cell
      response at 6 (+150 versus +219 cells/microl; P = 0.06) and 12 (+149 versus +215
      cells/microl; P = 0.39) months. Women with recent NVP exposure also had a trend
      towards elevated risk for clinical treatment failure (adjusted HR, 1.6; 95% CI,
      0.9-2.7). CONCLUSION: Exposure to maternal single-dose NVP was not associated
      with substantially different short-term treatment outcomes. However, evidence was
      suggestive that exposure within 6 months of ART initiation may be a risk factor
      for poor treatment outcomes, highlighting the importance of ART screening and
      initiation early in pregnancy.

PMID- 17457090
TI  - Treatment interruptions predict resistance in HIV-positive individuals purchasing
      fixed-dose combination antiretroviral therapy in Kampala, Uganda.
AB  - OBJECTIVE: To evaluate adherence, treatment interruptions, and outcomes in
      patients purchasing antiretroviral fixed-dose combination (FDC) therapy. DESIGN:
      Ninety-seven participants were recruited into a prospective 24-week observational
      cohort study of HIV-positive, antiretroviral-naive individuals initiating self
      pay Triomune or Maxivir therapy in Kampala, Uganda. Adherence was measured by
      monthly structured interview, unannounced home pill count, and electronic
      medication monitors (EMM). Treatment interruptions were measured as continuous
      intervals greater than 48 h without opening the EMM. The primary outcomes were
      survival with viral suppression below 400 copies/ml, CD4 cell increases, and
      genotypic drug resistance at 24 weeks. RESULTS: The median baseline CD4 cell
      count was 56 cells/microl and median log10 copies RNA/ml was 5.54; mean adherence
      ranged from 82 to 95% for all measures but declined significantly over time. In
      an intent-to-treat analysis, 70 (72%) patients had an undetectable plasma HIV-RNA
      level at week 24. Sixty-two of 95 (65%) individuals with continuous EMM data had
      a treatment interruption of greater than 48 h. Treatment interruptions accounted
      for 90% of missed doses. None of 33 participants who did not interrupt treatment
      for over 48 h had drug resistance, whereas eight of 62 (13%) participants who did
      interrupt therapy experienced drug resistance. Antiretroviral resistance was seen
      in 8% of individuals and overall mortality was 10% at 24 weeks. CONCLUSION: HIV
      positive individuals purchasing generic FDC antiretroviral therapy have high
      rates of adherence and viral suppression, low rates of antiretroviral resistance,
      and robust CD4 cell responses. Adherence is an important predictor of survival
      with full viral suppression. Treatment interruptions are an important predictor
      of drug resistance.

PMID- 17457092
TI  - Recent epidemic of acute hepatitis C virus in HIV-positive men who have sex with
      men linked to high-risk sexual behaviours.
AB  - OBJECTIVE: To characterize the mode of hepatitis C virus (HCV) transmission in a
      recent epidemic of acute HCV in HIV-infected individuals using linked molecular
      and clinical epidemiological studies. DESIGN: Individuals diagnosed with acute
      HCV between 1999 and 2005 at three urban HIV units in the UK were enrolled into a
      phylogenetic and case-control study. Phylogenetic trees were constructed from the
      amplified sequences of the E1/E2 region of the HCV genome and were used to
      compare cases with unrelated sequences. A questionnaire-based, case-control study
      using matched controls recruited from each HIV unit identified putative
      transmission factors. RESULTS: One hundred and eleven HIV-positive men who have
      sex with men with acute HCV (genotype 1: 84%) were enrolled. Phylogenetic
      analysis of 93 E1/E2 sequences revealed seven monophyletic clusters signifying
      multiple independent HCV lineages co-circulating in the HIV-positive population.
      Permucosal rather than percutaneous transmission factors were associated with
      case/control status. Cases (n = 60) had more sexual partners, increased levels of
      high-risk sexual behaviour and were more likely to have shared drugs via a nasal
      or anal route in the preceding year in comparison with controls (n = 130). Sex in
      a group of more than two people was the strongest predictor of case/control
      status; odds ratios associated with participation in two or at least three types
      of high-risk sexual behaviour in a group were 9.16 (95% confidence interval, 3.51
      23.90) and 23.50 (95% confidence interval, 9.47-58.33), respectively. CONCLUSION:
      The identified co-circulating HCV lineages belong to different subtypes and
      genotypes, implying that rather than viral change, the epidemic is due to
      permucosal transmission factors that should be the focus of public health
      interventions.

PMID- 17457091
TI  - HIV drug resistance surveillance for prioritizing treatment in resource-limited
      settings.
AB  - BACKGROUND: Sentinel testing programs for HIV drug resistance in resource-limited
      settings can inform policy on antiretroviral therapy (ART) and drug sequencing.
      OBJECTIVE: : To examine the value of resistance surveillance in influencing
      recommendations toward effective and cost-effective sequencing of ART regimens.
      METHODS: A state-transition model of HIV infection was adapted to simulate
      clinical care in Cote d'Ivoire and evaluate the incremental cost-effectiveness of
      (1) no ART; (2) ART beginning with a non-nucleoside reverse transcriptase
      inhibitor (NNRTI)-based regimen followed by a boosted protease inhibitor (PI)
      based regimen; and (3) ART beginning with a boosted PI-based regimen followed by
      an NNRTI-based regimen. RESULTS: At a 5% prevalence of NNRTI resistance, a
      strategy that started with a PI-based regimen had a smaller health benefit and
      higher cost-effectiveness ratio than a strategy that started with an NNRTI-based
      regimen (cost-effectiveness ratio $910/year of life saved). Results consistently
      favored initiation with an NNRTI-based regimen, regardless of the population
      prevalence of NNRTI resistance (up to 76%) and the efficacy of an NNRTI-based
      regimen in the setting of resistance. The most influential parameters on the cost
      effectiveness of sequencing strategies were boosted PI-based regimen costs and
      the efficacy of this regimen when used as second-line therapy. CONCLUSIONS: Drug
      costs and treatment efficacies, but not NNRTI resistance levels, were most
      influential in determining optimal HIV drug sequencing in Cote d'Ivoire. Results
      of surveillance for NNRTI resistance should not be used as a major guide to
      treatment policy in resource-limited settings.

PMID- 17457093
TI  - Twin pregnancy as a risk factor for mother-to-child transmission of HIV-1: trends
      over 20 years.
AB  - OBJECTIVE: We investigated whether twin pregnancies were at increased risk of
      mother-to-child HIV-1 transmission (MTCT), in comparison with singletons.
      METHODS: Among HIV-1 infected women enrolled in the French Perinatal HIV Cohort
      (n = 9262), we studied the association between twin deliveries and MTCT rate
      according to three time periods (pre-1994, 1994-1996, 1997-2004) and the effect
      of birth order. The mother was considered to have transmitted if at least one of
      the twins was infected. Univariate and multivariate analyses of risk factors for
      MTCT were performed for deliveries in the periods up to 1996. RESULTS: Overall,
      2.1% (192/9262) of all the deliveries were twins. The rate of prematurity was
      greater in twins than in singletons (54% and 13%, respectively). Up to 1996 the
      rate of MTCT of HIV-1 was 28.3% (15/53) in twin pregnancies, versus 13.5%
      (414/3077) in singletons [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.4
      4.7; P = 0.002; adjusted OR, 2.3: 95% CI, 1.1-2.3; P = 0.03). In the period from
      1997 to 2003, MTCT was low and did not differ between twins (1.0%) and singletons
      (1.8%; P = 1.0). Overall, the transmission rate for the first-born child was
      threefold that for the second-born child (14/164, 8.5% versus 4/164, 2.4%; P =
      0.008). CONCLUSION: Twin pregnancies were at increased risk of transmission, but
      in the era of HAART this risk was reduced for twins, as well as singletons.
      Management of multiple pregnancies should take into account the risks of
      premature rupture of the membranes and preterm delivery.

PMID- 17457095
TI  - Trends in HIV prevalence in blood donations in Europe, 1990-2004.
AB  - INTRODUCTION: The comparison of HIV prevalence among blood donations in European
      countries provides an indication of the relative safety of the blood supply in
      different countries and over time. METHODS: Data between 1990 and 2004 on annual
      numbers of blood donations and HIV prevalence in blood donations were collected
      from national correspondents in the 52 countries of the World Health Organization
      European Region. Data are presented for three geographic areas: West, Centre and
      East. RESULTS: Since 1990, the number of blood donations has declined by 43% in
      the East and by 26% in the Centre, while remaining relatively stable in the West.
      In 2004, the number of blood donations was more than twice as high in the West in
      comparison with the East and the Centre. Over the same period, HIV prevalence
      among blood donations increased dramatically in the East, remained stable in the
      Centre and declined in the West. Since 2001, HIV prevalence levels of more than
      10 per 100 000 donations were reported from six countries in the East (with a
      high of 128/100 000 in Ukraine), whereas in the rest of Europe the reported
      national HIV prevalence levels were lower than 10/100 000 donations. The
      prevalence of HIV was much lower among donations from repeat donors than from
      first-time donors. CONCLUSION: In some eastern European countries public health
      interventions, such as deferring individuals at risk of HIV infection from
      donating blood and constituting a pool of regular donors, are urgently needed to
      assure the safety of the blood supply.

PMID- 17457094
TI  - Microalbuminuria in HIV infection.
AB  - OBJECTIVE: Microalbuminuria is associated with increased risk of cardiovascular
      disease and mortality. The objective of the study was to evaluate if HIV
      infection was an independent risk factor for microalbuminuria. DESIGN: Cross
      sectional. METHODS: The relationship between HIV infection and microalbuminuria
      was assessed using subjects enrolled in the study of Fat Redistribution and
      Metabolic Change in HIV Infection, which consists of HIV-positive and control men
      and women. Participants with proteinuria (dipstick >or= 1+) were excluded.
      RESULTS: Microalbuminuria (urinary albumin/creatinine ratio, ACR > 30 mg/g) was
      present in 11% of HIV infected, and 2% of control participants (P < 0.001); a
      fivefold odds after multivariate adjustment (odds ratio, 5.11; 95% confidence
      interval, 1.97-13.31; P=0.0008). Several cardiovascular risk factors were
      associated with higher ACR in HIV participants: insulin resistance (HOMA > 4;
      32%, P < 0.0001), systolic blood pressure (21%, P = 0.01 for 120-140 versus < 120
      mmHg, and 43%, P = 0.06 for > 140 versus < 120 mmHg), and family history of
      hypertension (17%, P = 0.03). Higher CD4 cell count was associated with lower
      albumin/creatinine ratio (-24%, P = 0.009 for 200-400 versus < 200 cells/ml and 
      26%, P = 0.005 for > 400 versus < 200 cells/ml). CONCLUSION: HIV infection had a
      strong and independent association with microalbuminuria, the severity of which
      was predicted by markers of insulin resistance, hypertension, and advanced HIV
      infection. These associations warrant further investigation, as the increased
      prevalence of microalbuminuria in HIV infection may be a harbinger of future risk
      of cardiovascular and kidney diseases.

PMID- 17457096
TI  - Antiretroviral therapy and premature delivery in diagnosed HIV-infected women in
      the United Kingdom and Ireland.
AB  - OBJECTIVE: To explore the association between antiretroviral therapy in pregnancy
      and premature delivery, birthweight, stillbirth and neonatal mortality, in
      pregnancies in HIV-infected women delivering between 1990 and 2005. DESIGN:
      Pregnancies in women with diagnosed HIV infection in the UK and Ireland are
      notified to the National Study of HIV in Pregnancy and Childhood (NSHPC) through
      a well-established surveillance scheme. RESULTS: The prematurity rate (< 37 weeks
      gestation) was higher in women on highly active antiretroviral therapy (HAART)
      (14.1%, 476/3384) than in women on mono/dual therapy (10.1%, 107/1061), even
      after adjusting for ethnicity, maternal age, clinical status and injecting drug
      use as the source of HIV acquisition [adjusted odds ratio (AOR) = 1.51, 95%
      confidence interval (CI), 1.19-1.93; P = 0.001]. Delivery at < 35 weeks was even
      more strongly associated with HAART (AOR = 2.34; 95% CI, 1.64-3.37; P < 0.001).
      The effect was the same whether or not HAART included a protease inhibitor. In
      comparison with exposure to mono/dual therapy, exposure to HAART was associated
      with lower birthweight standardized for gestational age (P < 0.001), and an
      increased risk of stillbirth (AOR = 2.27; 95% CI, 0.96-5.41; P = 0.063).
      CONCLUSIONS: These findings, based on comprehensive population surveillance,
      demonstrate an increased risk of prematurity associated with HAART, and a
      possible association with other perinatal outcomes, including stillbirth and
      birthweight. Although the beneficial effects of antiretroviral therapy on mother
      to-child transmission are indisputable, monitoring antiretroviral therapy in
      pregnancy remains a priority.

PMID- 17457097
TI  - Pregnancy and the risk of HIV-1 acquisition among women in Uganda and Zimbabwe.
AB  - OBJECTIVE: Several studies have suggested that pregnancy is associated with an
      increased risk of HIV-1 acquisition. We used data from a large, prospective study
      of hormonal contraception and HIV-1 to evaluate the effect of pregnancy on the
      risk of HIV-1 acquisition. DESIGN: A multicenter prospective cohort study.
      METHODS: We examined 4439 women from family planning sites in Uganda and Zimbabwe
      contributing 31 369 follow-up visits during 1999-2004. Participants were aged 18
      35 years, and had received pregnancy and HIV-1 testing quarterly for 15-24
      months. Using proportional hazards modeling, we compared the time to HIV-1
      acquisition among four groups: pregnant women, non-pregnant lactating (NP/L)
      women, and women neither pregnant nor lactating (NP/NL) who were either using or
      not using hormonal contraception. RESULTS: A total of 211 participants became HIV
      1 infected (2.7 per 100 woman-years; wy), including 13 pregnant women (1.6 per
      100 wy), 33 NP/L women (2.7 per 100 wy), 126 NP/NL women using hormonal
      contraception (2.9 per 100 wy), and 39 NP/NL women not using hormonal
      contraception (2.7 per 100 wy). In multivariable analysis adjusting for site,
      age, living with partner, risky sexual behaviors, and incident vaginal, cervical
      and herpes simplex virus 2 infections, neither pregnant, NP/L, nor NP/NL women
      using hormonal contraception were at an increased risk of HIV-1 acquisition
      compared with NP/NL women not using hormonal contraception. CONCLUSION: Neither
      pregnancy nor lactation placed women at increased risk of HIV-1 acquisition in
      this multisite, prospective study of African women. This information is important
      in planning interventions to reduce HIV-1 acquisition among women.

PMID- 17457098
TI  - Evidence of a decline in transmitted HIV-1 drug resistance in the United Kingdom.
AB  - OBJECTIVE: To examine recent trends in transmitted drug resistance (TDR) in the
      United Kingdom. METHODS: Analysis of results of genotypic resistance tests
      reported to the UK HIV Drug Resistance Database, which includes virtually all
      tests conducted as part of routine clinical care nationally. Resistance was based
      on major mutations as defined in the 2005 International AIDS Society-USA
      guidelines. Analysis was restricted to persons who were antiretroviral treatment
      naive at the time of sampling, and a test defined as relating to recent infection
      if the patient was co-enrolled in the UK Register of HIV Seroconverters and the
      sample taken within 18 months of a negative HIV antibody test. RESULTS: A total
      of 4454 samples from treatment-naive patients between 1996 and 2004 were
      analysed, including 316 from patients recently infected at the time of the
      resistance test. After an initial rise, TDR declined from a peak of around 14% in
      2001-2002 to around 8% by the end of 2004 (Ptrend < 0.001), largely driven by a
      decrease in nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations. Non
      NRTI resistance has become increasingly important in relative terms and is now as
      common as NRTI resistance. Among patients with recent infection, an almost
      identical pattern was observed but shifted approximately 2 years earlier. A
      change in the distribution of viral subtypes did not explain these temporal
      trends. CONCLUSIONS: This is the first clear evidence of a decrease in TDR at
      national level. The wider use of regimens that suppress viral concentration to
      below infectious levels is one of several plausible explanations for this
      finding.

PMID- 17457099
TI  - Adherence to antiretroviral therapy in resource-limited settings: everything
      matters.

PMID- 17457100
TI  - Replication-competent HIV strains infect HIV controllers despite undetectable
      viremia (ANRS EP36 study).
AB  - The replicative potential of HIV-1 strains in a well-characterized group of eight
      HIV controllers was investigated. Replication-competent viruses were detected in
      CD4 T-cell co-culture supernatants from all HIV controllers. The phylogenetic
      analysis of C2V4 suggested viral evolution or co-infection or superinfection in
      two out of the four patients analysed. The vif and vpr genes were normal.
      Infection with HIV-1 variants with attenuated replicative capacity cannot be a
      general factor accounting for undetectable viraemia in HIV controllers.

PMID- 17457101
TI  - The GBV-C envelope glycoprotein E2 does not interact specifically with CD81.
AB  - The addition of GB virus C (GBV-C) E2 protein to cells inhibits HIV replication
      in vitro, presumably triggered by interactions with a specific cellular receptor.
      Indirect evidence suggests that CD81 is the GBV-C E2 cellular receptor. We found
      that E2 binding to cells was not dependent upon human CD81, and that soluble CD81
      did not compete with GBV-C E2 for cell binding. GBV-C E2 protein thus does not
      appear to interact with CD81.

PMID- 17457102
TI  - Relationship between serum IL-7 concentrations and lymphopenia upon different
      levels of HIV immune control.
AB  - Serum IL-7 levels correlate with T-cell depletion in HIV-infected individuals. In
      some patients, we observed that serum IL-7 decreases upon progression to AIDS,
      suggesting a role for IL-7 in T-cell maintenance in sporadic cases.
      Interestingly, IL-7 levels were significantly lower in stable long-term non
      progressors (LTNP) than in patients who lost the LTNP status in a 3-year follow
      up (P < 0.001), indicating that the serum IL-7 concentration might be a valuable
      marker for maintenance of the LTNP state.

PMID- 17457103
TI  - HIV-1 genetic diversity and compartmentalization in mother/infant pairs infected
      with CRF01_AE.
AB  - Molecular characterization of C2-V5 envelope sequences from maternal plasma,
      peripheral blood mononuclear cells (PBMC), cervical secretions and infant PBMC
      was performed in eight CRF01_AE-infected mother/infant pairs. Maternal viruses
      were relatively homogeneous within a compartment but distinct in different
      compartments in mothers with high CD4 cell counts. Infant viruses were almost
      distinct, but phylogenetically related, to maternal viruses, mostly from the
      maternal PBMC compartment, reflecting the frequent transmission of HIV-1 from
      maternal cells rather than free viruses.

PMID- 17457104
TI  - Steady-state lopinavir levels in third trimester of pregnancy.
AB  - Stek and colleagues reported low lopinavir levels in the third trimester of
      pregnancy at standard dosing. Since their initial report in 2003, we have taken
      steady-state trough lopinavir levels in all pregnant women in the third
      trimester; the results of 26 women on a lopinavir/ritonavir regimen are reported.
      The median trough level was 3.66 microg/ml, range 0.25-9.97; the median HIV viral
      load was 49 copies/ml at delivery. All infants were HIV polymerase chain reaction
      negative at 3 months.

PMID- 17457105
TI  - HIV-1 co-infection prevalence in two cohorts of early HIV-1 seroconverters in
      France.
AB  - Despite anecdotal reports of HIV-1 co-infections and super-infections, few large
      scale prevalence studies are available on multiple HIV-1 infection. We
      systematically searched for HIV-1 co-infections by means of a heteroduplex
      mobility assay in 660 HIV-1 seroconverters from the two ANRS SEROCO and PRIMO
      cohorts. Our results strongly suggest that HIV-1 co-infection remains a rare
      phenomenon in HIV-1 seroconverters infected in France between 1986 and 2004.

PMID- 17457106
TI  - HIV incidence and recent injections among adults in rural southwestern Uganda.
AB  - Thirty-six incident HIV cases were matched for age, sex and time period with 36
      controls to examine associations with recent injections. A significant
      association between HIV incidence and a history of injections was detected that
      was not reduced after adjusting for available sexual behaviour variables. This
      association could either be the result of injections causing HIV infection or,
      more likely, injections for seroconversion illnesses or other consequences of
      unsafe sex.

PMID- 17457107
TI  - Possible allergic cross-reaction to didanosine and tenofovir in an HIV-1-infected
      woman.

PMID- 17457108
TI  - Atazanavir-containing renal calculi in an HIV-infected patient.

PMID- 17457109
TI  - 'Forced treatment interruptions' and risk of HIV resistance in countries adopting
      law enforcement against marginalized populations.

PMID- 17457110
TI  - D-dimer levels are markedly raised in HIV-related thrombotic thrombocytopenic
      purpura.

PMID- 17457111
TI  - Thrombosis of a drug-eluting stent after almost 2 years in an HIV-infected
      patient.

PMID- 17457112
TI  - Nodular regenerative hyperplasia of liver as a consequence of ART.

PMID- 17457113
TI  - Rhodotorula mucilaginosa: an unusual cause of oral ulcers in AIDS patients.

PMID- 17457114
TI  - Psychosocial support for HIV-infected populations in developing countries: a key
      yet understudied component of positive prevention.

PMID- 17457116
TI  - Recrudescence of malignant hyperthermia.

PMID- 17457117
TI  - Communication and teamwork: essential to learn but difficult to measure.

PMID- 17457118
TI  - Neurostimulation/ultrasonography: the Trojan war will not take place.

PMID- 17457119
TI  - Drug-eluting coronary stents: what are the risks?

PMID- 17457120
TI  - Analysis of the clinical variables associated with recrudescence after malignant
      hyperthermia reactions.
AB  - BACKGROUND: Some patients develop recrudescence after a malignant hyperthermia
      (MH) reaction, but it is not clear which patients are at risk. The authors
      analyzed clinical variables associated with recrudescence after a clinical MH
      episode. METHODS: Data were obtained from Adverse Metabolic Reaction to
      Anesthesia reports in the North American Malignant Hyperthermia Registry.
      Patients who underwent general anesthesia and with an MH clinical grading score
      of 20 or greater, indicating a likely MH reaction, were included in this
      analysis. Patient characteristics, anesthetic agents, MH reaction clinical
      details, and postoperative outcomes were compared in the recrudescence and no
      recrudescence groups using chi-square tests and Z tests for categorical variables
      and the Student t test for continuous variables. Associations of clinical
      variables with recrudescence were assessed with univariate and multivariate
      logistic regression. RESULTS: Of 308 patients, 63 (20%) had recrudescence. The
      mean time from initial reaction to recrudescence was 13 h (SD = 13 h). Patients
      with recrudescence were more likely to have a muscular body type (P < 0.01),
      malignant hyperthermia score of 35 or greater (P < 0.01), a temperature increase
      (P < 0.01), and more than 150 min from induction to adverse reaction (P < 0.05).
      Muscular body type, a temperature increase, and a longer time from induction to
      initial malignant hyperthermia reaction were associated with recrudescence on
      multivariate logistic regression analysis. CONCLUSIONS: Recrudescence occurred in
      20% of patients. Muscular body types had a higher rate of recrudescence, perhaps
      associated with increased muscle mass. The risk of recrudescence increased as
      time from induction to the initial MH reaction increased, perhaps as a result of
      greater muscle exposure to triggering agents.

PMID- 17457121
TI  - Evaluating teamwork in a simulated obstetric environment.
AB  - BACKGROUND: The National Confidential Enquiry into Maternal Deaths identified
      "lack of communication and teamwork" as a leading cause of substandard obstetric
      care. The authors used high-fidelity simulation to present obstetric scenarios
      for team assessment. METHODS: Obstetric nurses, physicians, and resident
      physicians were repeatedly assigned to teams of five or six, each team managing
      one of four scenarios. Each person participated in two or three scenarios with
      differently constructed teams. Participants and nine external raters rated the
      teams' performances using a Human Factors Rating Scale (HFRS) and a Global Rating
      Scale (GRS). Interrater reliability was determined using intraclass correlations
      and the Cronbach alpha. Analyses of variance were used to determine the
      reliability of the two measures, and effects of both scenario and rater
      profession (R.N. vs. M.D.) on scores. Pearson product-moment correlations were
      used to compare external with self-generated assessments. RESULTS: The average of
      nine external rater scores showed good reliability for both HFRS and GRS;
      however, the intraclass correlation coefficients for a single rater was low.
      There was some effect of rater profession on self-generated HFRS but not on GRS.
      An analysis of profession-specific subscores on the HFRS revealed no interaction
      between profession of rater and profession being rated. There was low correlation
      between externally and self-generated team assessments. CONCLUSIONS: This study
      does not support the use of the HFRS for assessment of obstetric teams. The GRS
      shows promise as a summative but not a formative assessment tool. It is necessary
      to develop a domain specific behavioral marking system for obstetric teams.

PMID- 17457122
TI  - Submandible angle in nonobese patients with difficult tracheal intubation.
AB  - BACKGROUND: Although functional immobility of craniofacial structures during
      direct laryngoscopy may cause difficult tracheal intubation (DTI), there may be
      an unfavorable specific craniofacial feature for successful tracheal intubation.
      The aim of this study was to identify the specific craniofacial features
      associated with DTI. METHODS: Digital photographs of nonobese patients with DTI
      (23 males and 18 females) and age- and body mass index-matched patients with easy
      tracheal intubation (ETI) (16 males and 16 females) were taken and used for
      measurements of various craniofacial dimensions. Composite facial pictures of
      each patient group were constructed for visualization of differences of the
      craniofacial features. RESULTS: Mandible position angle was significantly smaller
      in DTI males than in male patients with ETI. Submandible angle was significantly
      larger in both male and female DTI patients than in patients with ETI. Logistic
      regression analysis revealed that the submandible angle was a significant and
      independent variable associated with DTI among the craniofacial dimensions for
      both sexes. The specific craniofacial features were visually more evident in the
      profile in than frontal composites. CONCLUSION: Increased submandible angle
      characterizes craniofacial features of patients with DTI.

PMID- 17457123
TI  - Pharmacokinetics and pharmacodynamics of propofol microemulsion and lipid
      emulsion after an intravenous bolus and variable rate infusion.
AB  - BACKGROUND: The aim of this trial was to evaluate the induction and recovery
      characteristics of microemulsion propofol (Aquafol; Daewon Pharmaceutical Co.,
      Ltd., Seoul, Korea). Pharmacokinetics, pharmacodynamics, and safety profile were
      investigated. Lipid emulsion propofol (Diprivan; AstraZeneca, London, United
      Kingdom) was used as a comparator. METHODS: Thirty-one healthy volunteers aged 20
      79 yr were given an intravenous bolus of propofol 2 mg/kg, followed by variable
      rate infusion for 60 min. Each volunteer was studied twice with different
      formulations at an interval of 1 week. Arterial concentrations of propofol were
      measured, and Bispectral Index was used as a surrogate measure of propofol
      effect. The induction and recovery characteristics including bioequivalence were
      evaluated by noncompartmental analysis. The pharmacokinetics and pharmacodynamics
      were investigated using a population approach with mixed effects modeling. The
      rate, severity, and causal relation of adverse events were analyzed. RESULTS:
      Both formulations were bioequivalent. The observed time to peak effect after a
      bolus of both formulations was 1.5 min. Plasma concentration of propofol at loss
      of consciousness, time to loss of consciousness after a bolus, and time to
      recovery of consciousness after discontinuation of infusion did not show
      significant differences. The population pharmacokinetics and pharmacodynamics
      revealed a variety of differences between two formulations. Aquafol showed
      similar safety profile to Diprivan. CONCLUSIONS: The efficacy and safety of
      Aquafol were not different from those of Diprivan within the dose range in this
      study.

PMID- 17457124
TI  - Early reversal of profound rocuronium-induced neuromuscular blockade by
      sugammadex in a randomized multicenter study: efficacy, safety, and
      pharmacokinetics.
AB  - BACKGROUND: Sugammadex reverses the neuromuscular blocking effects of rocuronium
      by chemical encapsulation. The efficacy, safety, and pharmacokinetics of
      sugammadex for reversal of profound rocuronium-induced neuromuscular blockade
      were evaluated. METHODS: Ninety-eight male adult patients were randomly assigned
      to receive sugammadex (1, 2, 4, 6, or 8 mg/kg) or placebo at 3, 5, or 15 min
      after 0.6 mg/kg rocuronium. Patients were anesthetized with propofol and
      fentanyl. The primary endpoint of the study was the time to achieve a recovery of
      train-of-four ratio to 0.9. Neuromuscular blockade was measured using
      acceleromyography. Concentrations of rocuronium and sugammadex were determined in
      venous blood and urine samples. A population pharmacokinetic model using NONMEM
      (GloboMax LLC, Hanover, MD) was applied. RESULTS: The mean time to recovery of
      the train-of-four ratio to 0.9 after dosing at 3, 5, and 15 min decreased from
      52.1, 51.7, and 35.6 min, respectively, after administration of placebo to 1.8,
      1.5, and 1.4 min, respectively, after 8 mg/kg sugammadex. Sugammadex was safe and
      well tolerated. However, 20.4% of patients showed signs of inadequate anesthesia
      after its administration. The median cumulative excretion of rocuronium in the
      urine over 24 h was 26% in the placebo group and increased to 58-74% after 4-8
      mg/kg sugammadex. The mean plasma clearances of sugammadex and rocuronium were
      0.084 and 0.26 l/min, respectively. CONCLUSIONS: In male subjects, sugammadex
      safely reversed profound neuromuscular blockade induced by 0.6 mg/kg rocuronium
      in a dose-dependent manner. Sugammadex enhanced the renal excretion of
      rocuronium, and its clearance is approximately one third that of rocuronium.

PMID- 17457125
TI  - Response to recruitment maneuver influences net alveolar fluid clearance in acute
      respiratory distress syndrome.
AB  - BACKGROUND: Alveolar fluid clearance is impaired in the majority of patients with
      acute respiratory distress syndrome (ARDS). Experimental studies have shown that
      a reduction of tidal volume increases alveolar fluid clearance. This study was
      aimed at assessing the impact of the response to a recruitment maneuver (RM) on
      net alveolar fluid clearance. METHODS: In 15 patients with ARDS, pulmonary edema
      fluid and plasma protein concentrations were measured before and after an RM,
      consisting of a positive end-expiratory pressure maintained 10 cm H2O above the
      lower inflection point of the pressure-volume curve during 15 min.
      Cardiorespiratory parameters were measured at baseline (before RM) and 1 and 4 h
      later. RM-induced lung recruitment was measured using the pressure-volume curve
      method. Net alveolar fluid clearance was measured by measuring changes in
      bronchoalveolar protein concentrations before and after RM. RESULTS: In
      responders, defined as patients showing an RM-induced increase in arterial oxygen
      tension of 20% of baseline value or greater, net alveolar fluid clearance (19 +/-
      13%/h) and significant alveolar recruitment (113 +/- 101 ml) were observed. In
      nonresponders, neither net alveolar fluid clearance (-24 +/- 11%/h) nor alveolar
      recruitment was measured. Responders and nonresponders differed only in terms of
      lung morphology: Responders had a diffuse loss of aeration, whereas nonresponders
      had a focal loss of aeration, predominating in the lower lobes. CONCLUSION: In
      the absence of alveolar recruitment and improvement in arterial oxygenation, RM
      decreases the rate of alveolar fluid clearance, suggesting that lung
      overinflation may be associated with epithelial dysfunction.

PMID- 17457126
TI  - Scopolamine prevents dreams during general anesthesia.
AB  - BACKGROUND: Dreaming during anesthesia is not a well-understood phenomenon.
      Anticholinergic drugs are used in anesthesia as premedication, but their use to
      decrease the incidence of dreams and psychological adverse reactions after
      anesthesia is not well established. The authors therefore studied the efficacy of
      intramuscular atropine and scopolamine for the prevention of dreams during
      general anesthesia with propofol and nitrous oxide. METHODS: Healthy women
      undergoing minor gynecologic surgery were randomly assigned to receive 2.5
      microg/kg scopolamine or 10 microg/kg atropine intramuscularly (n = 50/group). In
      both groups, anesthesia was induced and maintained with propofol as a 2.5-mg/kg
      bolus, followed by 12 mg x kg(-1) x h(-1) as a continuous infusion and 70%
      nitrous oxide in oxygen. Two interviews regarding dreaming activity and
      characteristics were conducted at 20 min and 6 h after surgery. RESULTS: None of
      the patients in the scopolamine group and 47% of the patients in the atropine
      group reported the occurrence of dreams 20 min after recovery. The results were
      similar at 6 h: 6% of the scopolamine group and 43% of the atropine group
      reported dream activity. No differences in sedation or anesthetic requirements
      were found. CONCLUSIONS: Previous studies in animals and humans suggest that
      dreams are affected by drugs acting on the central cholinergic system. The
      current results suggest that intramuscular scopolamine prevents dreams or dream
      recall in healthy young women undergoing short elective surgery with propofol
      nitrous oxide anesthesia.

PMID- 17457127
TI  - Myocardial depressant effects of desflurane: mechanical and electrophysiologic
      actions in vitro.
AB  - BACKGROUND: The authors determined whether desflurane altered myocardial
      excitation-contraction coupling and electrophysiologic behavior in the same
      manner as isoflurane and sevoflurane. METHODS: The effects of desflurane on
      isometric force in guinea pig ventricular papillary muscles were studied in
      modified standard and in 26 mM K(+) Tyrode solution with 0.1 microm
      isoproterenol. Desflurane effects on sarcoplasmic reticulum Ca(2+) release were
      also determined by examining its actions on rat papillary muscles, guinea pig
      papillary muscles in low-Na(+) Tyrode solution, and rapid cooling contractures.
      Normal and slow action potentials were recorded using a conventional
      microelectrode technique. Ca(2+) and K(+) currents of guinea pig ventricular
      myocytes were examined. RESULTS: Desflurane (5.3% and 11.6%) decreased peak force
      to approximately 70% and 40% of the baseline, respectively, similar to the
      effects of equianesthetic isoflurane concentrations. With isoproterenol in 26 mM
      K(+) Tyrode solution, desflurane markedly depressed late peaking force and
      modestly depressed early peak force. The rested state contractions of rat
      myocardium or guinea pig myocardium in low-Na(+) Tyrode solution were modestly
      depressed, whereas rapid cooling contractures were virtually abolished after
      desflurane administration. Desflurane significantly prolonged the action
      potential duration. Desflurane reduced L-type Ca(2+) current and the delayed
      outward K(+) current but did not alter the inward rectifier K(+) current.
      CONCLUSIONS: Myocardial depression by desflurane is due to decreased Ca(2+)
      influx, whereas depolarization-activated sarcoplasmic reticulum Ca(2+) release is
      modestly depressed, similar to the actions of isoflurane and sevoflurane.
      Desflurane depressed the delayed outward K(+) current associated with significant
      lengthening of cardiac action potentials.

PMID- 17457128
TI  - Molecular interaction of droperidol with human ether-a-go-go-related gene
      channels: prolongation of action potential duration without inducing early
      afterdepolarization.
AB  - BACKGROUND: The cardiac safety of droperidol given at antiemetic doses is a
      matter of debate. Although droperidol potently inhibits human ether-a-go-go
      related gene (HERG) channels, the molecular mode of this interaction is unknown.
      The role of amino acid residues typically mediating high-affinity block of HERG
      channels is unclear. It is furthermore unresolved whether droperidol at
      antiemetic concentrations induces action potential prolongation and
      arrhythmogenic early afterdepolarizations in cardiac myocytes. METHODS: Molecular
      mechanisms of HERG current inhibition by droperidol were established using two
      electrode voltage clamp recordings of Xenopus laevis oocytes expressing wild-type
      and mutant channels. The mutants T623A, S624A, V625A, Y652A, and F656A were
      generated by site-directed mutagenesis. The effect of droperidol on action
      potentials was investigated in cardiac myocytes isolated from guinea pig hearts
      using the patch clamp technique. RESULTS: Droperidol inhibited currents through
      HERG wild-type channels with a concentration of half-maximal inhibition of 0.6
      0.9 microM. Droperidol shifted the channel activation and the steady state
      inactivation toward negative potentials while channel deactivation was not
      affected. Current inhibition increased with membrane potential and with
      increasing duration of current activation. Inhibition of HERG channels was
      similarly reduced by all mutations. Droperidol at concentrations between 5 and
      100 nM prolonged whereas concentrations greater than 300 nm shortened action
      potentials. Early afterdepolarizations were not observed. CONCLUSIONS: Droperidol
      is a high-affinity blocker of HERG channels. Amino acid residues typically
      involved in high-affinity block mediate droperidol effects. Patch clamp results
      and computational modeling allow the hypothesis that interaction with calcium
      currents may explain why droperidol at antiemetic concentrations prolongs the
      action potential without inducing early afterdepolarizations.

PMID- 17457129
TI  - A comparison of epinephrine only, arginine vasopressin only, and epinephrine
      followed by arginine vasopressin on the survival rate in a rat model of
      anaphylactic shock.
AB  - BACKGROUND: Epinephrine and more recently arginine vasopressin (AVP) alone or in
      combination have been proposed in patients with anaphylactic shock, but few
      experimental data exist. The authors investigated the effects of epinephrine
      only, AVP only, or epinephrine followed by AVP in a model of anaphylactic shock.
      METHODS: Ovalbumin-sensitized Brown Norway rats were anesthetized, intubated, and
      shock induced with ovalbumin. Rats (n = 6/group) were randomly allocated to
      receive 5 min after shock onset: (1) saline (no-treatment group); (2) two boluses
      of epinephrine followed by continuous infusion (epinephrine group); (3) AVP bolus
      followed by continuous infusion (AVP group); (4) epinephrine bolus followed by
      AVP continuous infusion (epinephrine + AVP group). Mean arterial pressure (MAP)
      and skeletal muscle oxygen pressure (PtiO2) were measured. Continuous infusion
      rates were titrated to reach MAP values of 60 mmHg. Survival was analyzed.
      RESULTS: Without treatment, MAP and PtiO2 decreased rapidly with 0% survival. In
      the epinephrine group, MAP and PtiO2 recovered after an initial decrease, with
      84% survival. In the AVP group, MAP was partially restored and subsequently
      decreased; PtiO2 values decreased to values similar to those in the no-treatment
      group; survival was 0%. In the epinephrine + AVP group, MAP and PtiO2 values
      increased more slowly as compared with the epinephrine group; survival was 100%.
      CONCLUSIONS: In this model of anaphylactic shock, early treatment with
      epinephrine followed by continuous epinephrine or vasopressin infusion resulted
      in an excellent survival rate, whereas vasopressin only resulted in a 100% death
      rate. These experimental results suggest that epinephrine must still be
      considered as the first-line drug to treat anaphylactic shock.

PMID- 17457130
TI  - Isoflurane activates sarcolemmal adenosine triphosphate-sensitive potassium
      channels in vascular smooth muscle cells: a role for protein kinase A.
AB  - BACKGROUND: Recent evidence indicates that vascular adenosine triphosphate
      sensitive potassium (K(ATP)) channels in vascular smooth muscle cells are
      critical in the regulation of vascular tonus under both physiologic and
      pathophysiologic conditions. Studies of the interaction of volatile anesthetics
      with vascular K(ATP) channels have been limited. In the current study, the
      authors investigated the molecular mechanism of isoflurane's action on vascular
      K(ATP) channels. METHODS: Electrophysiologic experiments were performed using
      cell-attached and inside-out patch clamp techniques to monitor native vascular
      K(ATP) channels, and recombinant K(ATP) channels comprised of inwardly rectifying
      potassium channel subunits (Kir6.1) and the sulfonylurea receptor (SUR2B).
      Isometric tension experiments were performed in rat thoracic aortic rings without
      endothelium. RESULTS: Application of isoflurane (0.5 mM) to the bath solution
      during cell-attached recordings induced a significant increase in K(ATP) channel
      activity, which was greatly reduced by pretreatment with a selective inhibitor of
      protein kinase A (PKA), Rp-cAMPS (100 microM). In inside-out patches, isoflurane
      did not activate K(ATP) channels. Isoflurane significantly activated wild-type
      recombinant SUR2B/Kir6.1 in cell-attached patches. Isoflurane-induced activation
      of wild-type channels was diminished in the PKA-insensitive mutant SUR2B
      T633A/Kir6.1, SUR2B-S1465A/Kir6.1, and SUR2B/Kir6.1-S385A. In addition, the
      authors demonstrated that isoflurane-induced PKA activation was associated with
      isoflurane-induced decreases in isometric tension in the rat aorta. CONCLUSION:
      These results indicate that isoflurane activates K(ATP) channels via PKA
      activation. PKA-dependent vasodilation induced by isoflurane also was observed in
      isometric tension experiments. Analysis of expressed vascular-type K(ATP)
      channels suggested that PKA-mediated phosphorylation of both Kir6.1 and SUR2B
      subunits plays a pivotal role in isoflurane-induced vascular K(ATP) channel
      activation.

PMID- 17457131
TI  - A prospective, randomized comparison between ultrasound and nerve stimulation
      guidance for multiple injection axillary brachial plexus block.
AB  - BACKGROUND: This prospective, randomized, blinded study tested the hypothesis
      that ultrasound guidance can shorten the onset time of axillary brachial plexus
      block as compared with nerve stimulation guidance when using a multiple injection
      technique. METHODS: Sixty American Society of Anesthesiology physical status I
      III patients receiving axillary brachial plexus block with 20 ml ropivacaine,
      0.75%, using a multiple injection technique, were randomly allocated to receive
      either nerve stimulation (group NS, n = 30), or ultrasound guidance (group US, n
      = 30) for nerve location. A blinded observer recorded the onset of sensory and
      motor blocks, the need for general anesthesia (failed block) or greater than 100
      microg fentanyl (insufficient block) to complete surgery, procedure-related pain,
      success rate, and patient satisfaction. RESULTS: The median (range) number of
      needle passes was 4 (3-8) in group US and 8 (5-13) in group NS (P = 0.002). The
      onset of sensory block was shorter in group US (14 +/- 6 min) than in group NS
      (18 +/- 6 min) (P = 0.01), whereas no differences were observed in onset of motor
      block (24 +/- 8 min in group US and 25 +/- 8 min in group NS; P = 0.33) and
      readiness to surgery (26 +/- 8 min in group US and 28 +/- 9 min in group NS; P =
      0.48). No failed block was reported in either group. Insufficient block was
      observed in 1 patient (3%) of group US and 2 patients (6%) of group NS (P =
      0.61). Procedure-related pain was reported in 6 patients (20%) of group US and 14
      patients (48%) of group NS (P = 0.028); patient acceptance was similarly good in
      the two groups. CONCLUSION: Multiple injection axillary block with ultrasound
      guidance provided similar success rates and comparable incidence of complication
      as compared with nerve stimulation guidance.

PMID- 17457132
TI  - A review of neuraxial epidural morbidity: experience of more than 8,000 cases at
      a single teaching hospital.
AB  - BACKGROUND: The true incidence of serious neuraxial complications such as
      epidural hematoma or abscess after postoperative epidural infusions is still
      uncertain, in part due to inconsistencies in multicenter data collection.
      METHODS: Prospective data were collected over 16 yr from the authors' Acute Pain
      Service, which is based in a large tertiary teaching institution with a
      nonobstetric general surgical population. RESULTS: Over this period, 8,210
      epidural catheters were inserted for postoperative analgesia and 32 computed
      tomography or magnetic resonance imaging scans were undertaken to exclude
      potential neuraxial complications. From these, two spinal hematomas (1:4,105) and
      six epidural abscesses (1:1,368) were diagnosed. Only one patient required
      surgical decompression. There were no long-term neurologic sequelae in any
      patient. In the past 6 yr, the frequency of investigation and diagnosis of
      epidural abscess has increased. Overall, the combined rate of epidural abscess or
      hematoma was 1:1,026, (0.1%; 95% confidence interval, 0.04-0.19%) with a need for
      operative intervention of 1:8,210 (0.01%; 95% confidence interval, 0.0-0.07%).
      CONCLUSIONS: Spinal hematoma was very rare (< 0.05%). Epidural abscess was also
      rare (< 0.1%) but remains a potentially serious complication. Early diagnosis,
      using magnetic resonance imaging in patients with appropriate clinical
      indicators, before the onset of neurologic signs, enables conservative therapy in
      many cases and may help to prevent the development of serious neurologic
      sequelae.

PMID- 17457133
TI  - Risk factors for chronic pain after hysterectomy: a nationwide questionnaire and
      database study.
AB  - BACKGROUND: Women scheduled to undergo hysterectomy for benign indications
      frequently have preoperative pelvic pain, but it is largely unknown why pain in
      some cases persists or even develops after surgery. This nationwide questionnaire
      and database study describes pain and identifies risk factors for chronic
      postsurgical pain 1 yr after hysterectomy for benign indications. METHODS: A pain
      questionnaire was mailed to 1,299 women 1 yr after hysterectomy. The response
      rate was 90.3%, and the presence of persistent pain was correlated to indication
      for surgery, surgical procedure, type of anesthesia, and other perioperative
      data. RESULTS: Pain was reported by 31.9% 1 yr after hysterectomy (chronic pain),
      and 13.7% had pain more than 2 days a week. Pain was not present before surgery
      in 14.9% of women with chronic postsurgical pain. Risk factors for chronic pain
      were preoperative pelvic pain (odds ratio [OR], 3.25; 95% confidence interval
      [CI], 2.40-4.41), previous cesarean delivery (OR, 1.54; CI, 1.06-2.26), pain as
      the main indication for surgery (OR, 2.98; CI, 1.54-5.77), and pain problems
      elsewhere (OR, 3.19; CI, 2.29-4.44). Vaginal hysterectomy versus total abdominal
      hysterectomy was not significantly associated with a lower risk of chronic pain
      (OR, 0.70; CI, 0.46-1.06). Importantly, spinal versus general anesthesia was
      associated with less chronic pain (OR, 0.42; CI, 0.21-0.85). CONCLUSIONS: Thirty
      two percent had chronic pain after hysterectomy, and risk factors were comparable
      to those seen in other operations. Interestingly, spinal anesthesia was
      associated with a lower frequency of chronic pain, justifying prospective study
      of spinal anesthesia for patients with a high risk for development of chronic
      postsurgical pain.

PMID- 17457134
TI  - Constitutive cyclooxygenase-2 is involved in central nociceptive processes in
      humans.
AB  - BACKGROUND: Prostaglandins play a major role in inflammation and pain. They are
      synthesized by the two cyclooxygenase (COX) isoforms: COX-1, which is expressed
      constitutively in many cell types, and COX-2, which is induced at the site of
      inflammation. However, unlike peripheral tissues, COX-2 is expressed
      constitutively in the central nervous system and may play a role in nociceptive
      processes. The current study aimed to investigate the role of constitutive COX-2
      in the spinal transmission of nociceptive signals in humans. METHODS: The authors
      used 12 healthy volunteers to compare the effects of the specific COX-2 inhibitor
      sodium parecoxib (1 mg/kg) or placebo, administered intravenously in a double
      blind and crossover fashion, on the electrophysiologic recordings of the
      nociceptive flexion (RIII) reflex. The RIII reflex is an objective
      psychophysiologic index of the spinal transmission of nociceptive signals and was
      recorded from the biceps femoris after electrical stimulation of the sural nerve.
      Two experiments, 7 days apart, were conducted in each volunteer. On each
      experimental day, the effects of parecoxib or placebo were tested on (1) the RIII
      reflex threshold, (2) the stimulus-response curves of the reflex up to the
      tolerance threshold (frequency of stimulation: 0.1 Hz), and (3) the progressive
      increase of the reflex and pain sensations (i.e., "windup" phenomenon) induced by
      a series of 15 stimulations at a frequency of 1 Hz (intensity 20% above RIII
      threshold). RESULTS: Parecoxib, but not placebo, significantly reduced the slope
      of the stimulus-response curve, suggesting a reduction in the gain of the spinal
      transmission of nociceptive signals. By contrast, the windup phenomenon was not
      significantly altered after administration of parecoxib or placebo. CONCLUSIONS:
      This study shows that constitutive COX-2 modulates spinal nociceptive processes
      and that the antiinflammatory and antinociceptive actions of COX-2 inhibitors are
      not necessarily related.

PMID- 17457135
TI  - Oral donepezil reduces hypersensitivity after nerve injury by a spinal muscarinic
      receptor mechanism.
AB  - BACKGROUND: Cholinesterase inhibitors which reach the central nervous system
      produce pain relief but are poorly tolerated because of gastrointestinal side
      effects. Here, the authors tested whether donepezil, a central nervous system
      penetrant cholinesterase inhibitor with a low incidence of gastrointestinal side
      effects, would relieve hypersensitivity in an animal model of neuropathic pain.
      METHODS: Male rats were anesthetized, and the L5 and L6 spinal nerves were
      ligated unilaterally. Hypersensitivity was measured by withdrawal threshold to
      von Frey filament application to the hind paw after oral donepezil, and
      antagonists administered centrally and peripherally. Efficacy of chronic oral
      donepezil to relieve hypersensitivity was tested, and activation of G proteins by
      M(2) muscarinic receptors was determined by carbachol-stimulated [(35)S]guanosine
      triphosphate (gamma)S autoradiography in brain and spinal cord. RESULTS: Spinal
      nerve ligation resulted in hypersensitivity that was more severe ipsilateral than
      contralateral to surgery. Oral donepezil reduced hypersensitivity bilaterally in
      a dose-dependent manner for 2 h, and this effect was blocked by spinal but not
      supraspinal or peripheral muscarinic receptor antagonism. Oral donepezil
      maintained efficacy over 2 weeks of twice daily administration, and this
      treatment did not lead to desensitization of muscarinic receptor-coupled G
      proteins in brain or spinal cord. CONCLUSIONS: Donepezil, a well-tolerated
      cholinesterase inhibitor used in the treatment of Alzheimer dementia, reduces
      hypersensitivity in this rat model of neuropathic pain by actions on muscarinic
      receptors in the spinal cord. Lack of tolerance to this effect, in contrast to
      rapid tolerance to direct receptor agonists, suggests that cholinesterase
      inhibition may be useful in the treatment of neuropathic pain.

PMID- 17457136
TI  - Effects of intermittent femoral nerve injections of bupivacaine, levobupivacaine,
      and ropivacaine on mitochondrial energy metabolism and intracellular calcium
      homeostasis in rat psoas muscle.
AB  - BACKGROUND: Long-acting local anesthetics cause muscle damage. Moreover, long
      acting local anesthetics act as uncoupler of oxidative phosphorylation in
      isolated mitochondria and enhance sarcoplasmic reticulum Ca(2+) release. The aim
      of the study was to evaluate effects of perineural injections of local
      anesthetics on mitochondrial energetic metabolism and intracellular calcium
      homeostasis in vivo. METHODS: Femoral nerve block catheters were inserted in
      adult male Wistar rats. Rats were randomized and received seven injections (1
      ml/kg) of bupivacaine, levobupivacaine, ropivacaine, or isotonic saline at 8-h
      intervals. Rats were killed 8 h after the last injection. Psoas muscle was
      quickly dissected from next to the femoral nerve. Local anesthetic concentrations
      in muscle were determined. Oxidative capacity was measured in saponin-skinned
      fibers. Oxygen consumption rates were measured, and mitochondrial adenosine
      triphosphate synthesis rate was determined. Enzymatic activities of mitochondrial
      respiratory chain complexes were evaluated. Local calcium release events (calcium
      sparks) were analyzed as well as sarcoplasmic reticulum calcium content in
      saponin-skinned fibers. RESULTS: Eight hours after the last injection, psoas
      muscle concentration of local anesthetics was less than 0.3 microg/g tissue.
      Adenosine triphosphate synthesis and adenosine triphosphate-to-oxygen ratio were
      significantly decreased in the muscle of rats treated with local anesthetics. A
      global decrease (around 50%) in all of the enzyme activities of the respiratory
      chain was observed. Levobupivacaine increased the amplitude and frequency of the
      calcium sparks, whereas lower sarcoplasmic reticulum calcium content was shown.
      CONCLUSION: Bupivacaine, levobupivacaine, and ropivacaine injected via femoral
      nerve block catheters induce a deleterious effect in mitochondrial energy,
      whereas only levobupivacaine disturbs calcium homeostasis.

PMID- 17457137
TI  - Patient-requested neuraxial analgesia for labor: impact on rates of cesarean and
      instrumental vaginal delivery.
AB  - A systematic review, including a meta-analysis, on the timing effects of
      neuraxial analgesia (NA) on cesarean and instrumental vaginal deliveries in
      nulliparous women was conducted. Of 20 articles identified, 9 met the inclusion
      quality criteria (3,320 participants). Cesarean delivery (odds ratio, 1.00; 95%
      confidence interval, 0.82-1.23) and instrumental vaginal delivery (odds ratio,
      1.00; 95% confidence interval, 0.83-1.21) rates were similar in the early NA and
      control groups. Neonates of women with early NA had a higher umbilical artery pH
      and received less naloxone. In the early NA group, fewer women were not compliant
      with assigned treatment and crossed over to the control group. Women receiving
      early NA for pain relief are not at increased risk of operative delivery, whereas
      those receiving early parenteral opioid and late epidural analgesia present a
      higher risk of instrumental vaginal delivery for nonreassuring fetal status,
      worse indices of neonatal wellness, and a lower quality of maternal analgesia.

PMID- 17457138
TI  - A tale of two paintings: depictions of the first public demonstration of ether
      anesthesia.

PMID- 17457139
TI  - Hyperoxia-induced tissue hypoxia: a danger?

PMID- 17457140
TI  - Late thrombosis of a drug-eluting stent presenting in the perioperative period.

PMID- 17457141
TI  - Etomidate-induced pacemaker-mediated ventricular tachycardia.

PMID- 17457142
TI  - beta-Blockade abolishes anesthetic preconditioning: impact on clinical
      applicability.

PMID- 17457144
TI  - Takotsubo cardiomyopathy after general anesthesia.

PMID- 17457145
TI  - Ganglion impar injection techniques for coccydynia (coccyx pain) and pelvic pain.

PMID- 17457146
TI  - beta-Blockade Abolishes Anesthetic Preconditioning: Impact on Clinical
      Applicability.

PMID- 17457147
TI  - Oxycodone's mechanism of action and potency differences after spinal and systemic
      routes of administration.

PMID- 17457150
TI  - Lower tidal volumes and positive end-expiratory pressure prevents alveolar
      coagulation in patients without lung injury.

PMID- 17457151
TI  - An unusual cause of leak in a silicone endotracheal tube secured by the
      SecureEasy endotracheal tube holder in the trauma intensive care unit.

PMID- 17457152
TI  - Coronary artery stent placement immediately before noncardiac surgery: a
      potential risk?

PMID- 17457153
TI  - A new twist in approaching difficult tracheal intubation. Description of an
      economic, easy, and effective way: the sigma way.

PMID- 17457156
TI  - Morbidity and mortality following breast cancer surgery in women: national
      benchmarks for standards of care.
AB  - BACKGROUND: Most reports on postoperative (OP) morbidity and mortality following
      breast cancer surgery (BCS) are limited by relatively small sample size resulting
      in a lack of national benchmarks for quality of care. This paper reports the 30
      day morbidity and mortality following BCS in women using a large prospective
      multi-institutional database. METHODS: The National Surgical Quality Improvement
      Program Patient Safety in Surgery, prospectively collected inpatient and
      outpatient 30 day postoperative morbidity and mortality data on patients
      undergoing surgery at 14 university and 4 community centers. Using the procedure
      CPT code, the database was queried for all women undergoing mastectomy (MT) or
      lumpectomy with an axillary procedure (L-ANP). Morbidity and mortality were
      categorized as mortality, wound, cardiac, renal, pulmonary, and central nervous
      system. Logistic regression models for the prediction of wound complications were
      developed. Preoperative variables having bivariate relationships with
      postoperative wound complications with P < or = 0.20 were submitted for
      consideration. RESULTS: We identified 1660 and 1447 women who underwent MT and l
      ANP, respectively. The mean age was 55.9 years. The majority of procedures were
      under general anesthesia. The 30-day postoperative mortality for MT and l-ALNP
      were 0.24% and 0%, respectively. The most frequent morbid complication was wound
      infection, more commonly occurring in the mastectomy (4.34%) group versus the
      lumpectomy group (1.97%). Cardiac and pulmonary complications occurred
      infrequently in the mastectomy group (cardiac: MT, 0.12%; and pulmonary: MT,
      0.66%). There were no cardiac or pulmonary complications in the lumpectomy group.
      CNS morbidities were rare in both surgical groups (MT, 0.12%; and l-ALNP, 0.07%).
      Development of a UTI was more common in women who underwent a mastectomy (0.66%)
      when compared with women that had a lumpectomy (0.14%). The only significant
      predictors of a wound complication were morbid obesity (BMI >30), having had a
      MT, low preoperative albumin and hematocrit greater than 45%. CONCLUSION:
      Morbidity and mortality rates following BCS in women are low, limiting their
      value in assessing quality of care. Mastectomy carries higher complication rate
      than l-ANP with wound infection being the most common.

PMID- 17457157
TI  - Quality of benchmarks for assessment of care will influence outcome.

PMID- 17457158
TI  - Early antibiotic treatment for severe acute necrotizing pancreatitis: a
      randomized, double-blind, placebo-controlled study.
AB  - BACKGROUND & AIMS: In patients with severe, necrotizing pancreatitis, it is
      common to administer early, broad-spectrum antibiotics, often a carbapenem, in
      the hope of reducing the incidence of pancreatic and peripancreatic infections,
      although the benefits of doing so have not been proved. METHODS: A multicenter,
      prospective, double-blind, placebo-controlled randomized study set in 32 centers
      within North America and Europe. PARTICIPANTS: One hundred patients with
      clinically severe, confirmed necrotizing pancreatitis: 50 received meropenem and
      50 received placebo. INTERVENTIONS: Meropenem (1 g intravenously every 8 hours)
      or placebo within 5 days of the onset of symptoms for 7 to 21 days. MAIN OUTCOME
      MEASURES: Primary endpoint: development of pancreatic or peripancreatic infection
      within 42 days following randomization. Other endpoints: time between onset of
      pancreatitis and the development of pancreatic or peripancreatic infection; all
      cause mortality; requirement for surgical intervention; development of
      nonpancreatic infections within 42 days following randomization. RESULTS:
      Pancreatic or peripancreatic infections developed in 18% (9 of 50) of patients in
      the meropenem group compared with 12% (6 of 50) in the placebo group (P = 0.401).
      Overall mortality rate was 20% (10 of 50) in the meropenem group and 18% (9 of
      50) in the placebo group (P = 0.799). Surgical intervention was required in 26%
      (13 of 50) and 20% (10 of 50) of the meropenem and placebo groups, respectively
      (P = 0.476). CONCLUSIONS: This study demonstrated no statistically significant
      difference between the treatment groups for pancreatic or peripancreatic
      infection, mortality, or requirement for surgical intervention, and did not
      support early prophylactic antimicrobial use in patients with severe acute
      necrotizing pancreatitis.

PMID- 17457159
TI  - As good as it gets: the study of prophylactic antibiotics in severe acute
      pancreatitis.

PMID- 17457160
TI  - Intraoperative blood salvage during liver resection: a randomized controlled
      trial.
AB  - OBJECTIVE: A randomized controlled trial was conducted to clarify the
      effectiveness of intraoperative blood salvage in reducing blood loss. BACKGROUND:
      Although reduction of central venous pressure (CVP) is thought to decrease blood
      loss during liver resection, no consistently effective and safe method for
      obtaining the desired reduction of CVP has been established. METHODS: Living
      liver donors scheduled to undergo liver graft procurement were randomly assigned
      to a blood salvage group, in which a blood volume equal to approximately 0.7% of
      the patient's body weight was collected before the liver transection, or a
      control group. The surgeons were blinded to the randomization results. The
      primary outcome measure was blood loss during liver parenchymal division. A
      multivariate analysis was also performed. RESULTS: Seventy-nine donors were
      allocated intraoperatively to the blood salvage group (n = 40) or the control
      group (n = 39). The amount of blood loss during liver transection was
      significantly smaller in the blood salvage group than in the control group
      (median loss during transection, 140 mL vs. 230 mL, P = 0.034). The CVP at the
      beginning of the liver parenchymal division was significantly lower in the blood
      salvage group than in the control group (median, 5 cm H2O vs. 6 cm H2O, P =
      0.005). The results of a multivariate analysis revealed that intraoperative blood
      salvage offered the advantage of reduced blood loss during liver parenchymal
      division (adjusted OR, 0.31; 95% CI, 0.11-0.85, P = 0.025). CONCLUSION: Modest
      intraoperative blood salvage significantly and safely reduced blood loss during
      hepatic parenchymal transection.

PMID- 17457161
TI  - Conventional versus binding pancreaticojejunostomy after pancreaticoduodenectomy:
      a prospective randomized trial.
AB  - OBJECTIVE: This study compared the postoperative pancreatic anastomosis leakage
      rate of a new binding technique with the conventional technique of
      pancreaticojejunostomy after pancreaticoduodenectomy. SUMMARY BACKGROUND DATA:
      Leakage from pancreatic anastomoses remains the single most important morbidity
      after pancreaticoduodenectomy and contributes to prolonged hospitalization and
      mortality. The reported incidence after conventional pancreaticojejunostomy
      ranged from 10% to 29%. We previously reported a new binding
      pancreaticojejunostomy technique with a leakage of 0%. METHODS: We conducted a
      prospective randomized study on 217 patients who underwent
      pancreaticoduodenectomy for benign and malignant diseases of the pancreatic head
      and the periampullary region comparing the 2 techniques of
      pancreaticojejunostomy. RESULTS: Of the 111 patients randomized to the
      conventional group, pancreaticojejunostomy leakage occurred in 8 patients, while
      no patient in the 106 patients randomized to the binding group developed leakage
      (chi test, P = 0.014). The overall postoperative complications developed in 41
      patients (36.9%) in the conventional group compared with 26 patients (24.5%) in
      the binding group (chi test, P = 0.048). Seven patients (6.3%) died in the
      perioperative period in the conventional group compared with 3 patients (2.8%) in
      the binding group (chi test, P = 0.37). The postoperative hospital stay (mean +/-
      SD) for the conventional group was 22.4 +/- 10.9 days, which was significantly
      longer than the binding group (18.4 +/- 4.7 days) (Mann-Whitney U test, P <
      0.001). CONCLUSIONS: Binding pancreaticojejunostomy after panceaticoduodenectomy
      significantly decreased postoperative complication and pancreaticojejunostomy
      leakage rates and shortened hospital stay when compared with conventional
      pancreaticojejunostomy.

PMID- 17457162
TI  - A state-wide review of contemporary outcomes of gastric bypass in Florida: does
      provider volume impact outcomes?
AB  - OBJECTIVES: To report contemporary outcomes of gastric bypass for obesity and to
      assess the relationship between provider volume and outcomes. BACKGROUND: Certain
      Florida-based insurers are denying patients access to bariatric surgery because
      of alleged high morbidity and mortality. SETTINGS AND PATIENTS: The prospectively
      collected and mandatory-reported Florida-wide hospital discharge database was
      analyzed. Restrictive procedures such as adjustable gastric banding and
      gastroplasty were excluded. RESULTS: The overall complication and in-hospital
      mortality rates in 19,174 patients who underwent gastric bypass from 1999 to 2003
      were 9.3% (8.9-9.7) and 0.28% (0.21-0.36), respectively. Age and male gender were
      associated with increased duration of hospital stay (P < 0.001), increased in
      hospital complications [age: odds ratio (OR) = 1.11, CI: 1.08-1.13; male: OR =
      1.53, CI: 0.36-1.72] and increased in-hospital mortality (age: OR = 1.51, CI:
      1.32-1.73; male: CI = 2.66, CI: 1.53-4.63), all P < 0.001. The odds of in
      hospital complications significantly increased with diminishing surgeon or
      hospital procedure volume (surgeon: OR = 2.0, CI: 1.3-3.1; P < 0.001, 1-5
      procedures relative to >500 procedures; hospital volume: OR = 2.1, CI: 1.2-3.5; P
      < 0.001, 1-9 procedures relative to >500 procedures). The percent change of in
      hospital mortality in later years of the study was lowest, indicating higher
      mortality rates, for surgeons or hospitals with fewer (< or =100) compared with
      higher (> or =500) procedures. CONCLUSION: Increased utilization of bariatric
      surgery in Florida is associated with overall favorable short-term outcomes.
      Older age and male gender were associated with increased morbidity and mortality.
      Surgeon and hospital procedure volume have an inverse relationship with in
      hospital complications and mortality.

PMID- 17457163
TI  - Long-term outcomes following neoadjuvant chemoradiotherapy for esophageal cancer.
AB  - OBJECTIVE: We present and analyze long-term outcomes following multimodal therapy
      for esophageal cancer, in particular the relative impact of histomorphologic
      tumor regression and nodal status. PATIENTS AND METHODS: A total of 243 patients
      [(adenocarcinoma (n = 170) and squamous cell carcinoma (n = 73)] treated with
      neoadjuvant chemoradiotherapy in the period 1990 to 2004 were followed
      prospectively with a median follow-up of 60 months. Pathologic stage and tumor
      regression grade (TRG) were documented, the site of first failure was recorded,
      and Kaplan-Meier survival curves were plotted. RESULTS: Thirty patients (12%) did
      not undergo surgery due to disease progression or deteriorated performance
      status. Forty-one patients (19%) had a complete pathologic response (pCR), and
      there were 31(15%) stage I, 69 (32%) stage II, and 72 (34%) stage III cases. The
      overall median survival was 18 months, and the 5-year survival was 27%. The 5
      year survival of patients achieving a pCR was 50% compared with 37% in non-pCR
      patients who were node-negative (P = 0.86). Histomorphologic tumor regression was
      not associated with pre-CRT cTN stage but was significantly (P < 0.05) associated
      with ypN stage. By multivariate analysis, ypN status (P = 0.002) was more
      predictive of overall survival than TRG (P = 0.06) or ypT stage (P = 0.39).
      CONCLUSION: Achieving a node-negative status is the major determinant of outcome
      following neoadjuvant chemoradiotherapy. Histomorphologic tumor regression is
      less predictive of outcome than pathologic nodal status (ypN), and the need to
      include a primary site regression score in a new staging classification is
      unclear.

PMID- 17457164
TI  - An evaluation of prognostic factors and tumor staging of resected carcinoma of
      the esophagus.
AB  - OBJECTIVE: To evaluate prognostic factors and tumor staging in patients after
      esophagectomy for cancer. SUMMARY BACKGROUND DATA: Several reports have
      questioned the appropriateness of the sixth edition of the International Union
      Against Cancer (UICC) TNM guidelines for staging esophageal cancer. Additional
      pathologic characteristics, besides the 3 basic facets of anatomic spread (tumor,
      node, metastases), might also have prognostic value. METHODS: All patients who
      underwent resection of the esophagus for carcinoma between January 1995 and March
      2003 were extracted from a prospective database. Univariate and multivariate
      analysis was performed to identify prognostic factors for survival. The goodness
      of fit and accuracy of 3 staging models (UICC-TNM, Korst classification, Rice
      classification) predicting survival were assessed. RESULTS: A total of 292
      patients (mean age, 63 years) underwent esophagectomy. The 5-year overall
      survival rate was 29% (median, 21 months). pT-, pN-, pm-stage, and radicality of
      the resection were independent prognostic factors. Subdivision of T1 tumors into
      mucosal and submucosal showed significant differences in 5-year survival between
      both groups: 90% versus 47%, respectively (P = 0.01). Subdivision of pN-stage
      into 3 groups based on the number of positive nodes (0, 1-2, and >3 nodes
      positive) or the lymph node ratio (0, 0.01-0.2, and >0.2) also refined staging (P
      = 0.001 and P < 0.001, respectively). The current subclassification of M1 (M1a
      and M1b) is not warranted (P = 0.41). The staging model of Rice was more accurate
      than the UICC-TNM classification in predicting survival. CONCLUSION: This study
      supports the view that the current (6th edition) UICC-TNM staging model for
      esophageal cancer needs to be revised.

PMID- 17457165
TI  - Is the increasing rate of local excision for stage I rectal cancer in the United
      States justified?: a nationwide cohort study from the National Cancer Database.
AB  - OBJECTIVE: Determine rates of local excision (LE) over time, and test the
      hypothesis that LE carries increased oncologic risks but reduced perioperative
      morbidity when compared with standard resection (SR). SUMMARY BACKGROUND DATA:
      Despite the lack of level I/level II evidence supporting its oncologic adequacy,
      LE is performed for stage I rectal cancer. METHODS: Surgical therapy for 35,179
      patients with stage I rectal cancer diagnosed in 1989 to 2003 was examined over
      time, utilizing the National Cancer Database. A special study then analyzed
      perioperative outcomes, local recurrence and survival in 2124 patients diagnosed
      between 1994 and 1996, including 765 (T1, 601; T2, 164) treated by LE and 1359
      (T1, 493; T2, 866) treated by SR. RESULTS: From 1989 to 2003, the use of LE has
      increased (T1, 26.6-43.7%; T2, 5.8-16.8%; P < 0.001 both). The special study
      demonstrated significantly lower 30-day morbidity after LE versus SR (5.6% vs.
      14.6%; P < 0.001). After adjusting for patient and tumor characteristics, the 5
      year local recurrence after LE versus SR was 12.5 versus 6.9% (P = 0.003; hazard
      ratio = 0.38; 95% CI, 0.23-0.62) for T1 tumors, and 22.1 versus 15.1% (P = 0.01;
      hazard ratio = 0.69; 95% CI, 0.44-1.07) for T2 tumors. The 5-year overall
      survival (T1, 77.4% vs. 81.7%, P = 0.09; T2, 67.6% vs. 76.5%, P = 0.01) was
      influenced by age and comorbidities but not the type of surgery. CONCLUSIONS:
      This study provides the best evidence for both the increasing use and the
      associated risks of LE versus SR. For each individual patient, the benefits of LE
      must be balanced against the heightened risk of local failure.

PMID- 17457166
TI  - Endogenous endotoxin participates in causing a panenteric inflammatory ileus
      after colonic surgery.
AB  - OBJECTIVE: To investigate muscularis inflammation and endogenous endotoxin as
      causes of postoperative ileus. BACKGROUND: Postoperative inflammatory ileus of
      the colon is associated with a significant delay in gastrointestinal transit. We
      investigated whether these changes are caused by the downstream obstructive
      barrier of the surgically altered colon or by small intestinal muscularis
      inflammation itself. Furthermore, we evaluated the mechanistic role of gut
      derived endotoxin in the development of postoperative intestinal dysfunction.
      METHODS: Rats underwent surgical manipulation of the colon. Isolated
      gastrointestinal transit was analyzed in animals with ileostomy. The
      perioperative emigration of intracolonic particles was investigated by colonic
      luminal injection of fluorescently labeled LPS and microspheres. Mediator mRNA
      induction was quantified by real-time RT-PCR. Muscularis leukocytic infiltrates
      were characterized. In vitro circular muscle contractility was assessed in a
      standard organ bath. RESULTS: Ileostomy rats presented with a significant delay
      in small intestinal transit after colonic manipulation. This was associated with
      leukocyte recruitment and inflammatory mediator mRNA induction within the small
      intestinal muscularis. Colonic manipulation caused the transference of
      intracolonic LPS and microspheres into the intestinal muscularis. Postoperative
      in vitro small intestinal circular muscle contractility was impaired by 42%
      compared with controls. Gut decontamination and TLR-4 deletion significantly
      alleviated the small intestinal muscularis inflammation and prevented intestinal
      muscle dysfunction. CONCLUSIONS: Selective colonic manipulation initiates a
      distant inflammatory response in the small intestinal muscularis that contributes
      to postoperative ileus. The data provide evidence that gut-derived bacterial
      products are mechanistically involved in the initiation of this remote
      inflammatory cascade.

PMID- 17457167
TI  - Early assessment of pancreatic infections and overall prognosis in severe acute
      pancreatitis by procalcitonin (PCT): a prospective international multicenter
      study.
AB  - BACKGROUND: Pancreatic infections and sepsis are major complications in severe
      acute pancreatitis (AP) with significant impact on management and outcome. We
      investigated the value of Procalcitonin (PCT) for identifying patients at risk to
      develop pancreatic infections in severe AP. METHODS: A total of 104 patients with
      predicted severe AP were enrolled in five European academic surgical centers
      within 96 hours of symptom onset. PCT was measured prospectively by a semi
      automated immunoassay in each center, C-reactive protein (CRP) was routinely
      assessed. Both parameters were monitored over a maximum of 21 consecutive days
      and in weekly intervals thereafter. RESULTS: In contrast to CRP, PCT
      concentrations were significantly elevated in patients with pancreatic infections
      and associated multiorgan dysfunction syndrome (MODS) who all required surgery (n
      = 10) and in nonsurvivors (n = 8) early after onset of symptoms. PCT levels
      revealed only a moderate increase in patients with pancreatic infections in the
      absence of MODS (n = 7), all of whom were managed nonoperatively without
      mortality. A PCT value of > or =3.5 ng/mL on 2 consecutive days was superior to
      CRP > or =430 mg/L for the assessment of infected necrosis with MODS or
      nonsurvival as determined by ROC analysis with a sensitivity and specificity of
      93% and 88% for PCT and 40% and 100% for CRP, respectively (P < 0.01). The single
      or combined prediction of the two major complications was already possible on the
      third and fourth day after onset of symptoms with a sensitivity and specificity
      of 79% and 93% for PCT > or =3.8 ng/mL compared with 36% and 97% for CRP > or
      =430 mg/L, respectively (P = 0.002). CONCLUSION: Monitoring of PCT allows early
      and reliable assessment of clinically relevant pancreatic infections and overall
      prognosis in AP. This single test parameter significantly contributes to an
      improved stratification of patients at risk to develop major complications.

PMID- 17457168
TI  - Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single
      institution.
AB  - OBJECTIVE: To assess long-term survival and prognostic factors in a large series
      of patients with bile duct cancer. SUMMARY BACKGROUND DATA: The incidence of bile
      duct cancer is low but increasing. Determinants of survival vary in the
      literature, due to a lack of sufficient numbers of patients in most series.
      METHODS: We studied 564 consecutive patients with bile duct cancer operated upon
      between 1973 and 2004. Patients were divided into intrahepatic, perihilar, and
      distal groups. Principle outcome measures were complications, 30-day mortality,
      and survival. RESULTS: Of the 564 patients, 44 (8%) had intrahepatic, 281 (50%)
      had perihilar, and 239 (42%) had distal tumors. Approximately half (294, 52%)
      were treated before 1995, while 270 (48%) were treated thereafter. The
      perioperative mortality rate was 4%. In log-rank analyses, survival was higher in
      the later time period (P = 0.002), in patients with intrahepatic disease (P =
      0.001), with negative resection margins (P < 0.001), with well/moderately
      differentiated tumors (P < 0.001), and those with negative lymph nodal status (P
      < 0.001). In multivariate analysis, negative margins (P < 0.001), tumor
      differentiation (P < 0.001), and negative nodal status (P < 0.001), but not tumor
      diameter, were significant independent prognostic factors. In R0-resected
      patients, lymph node status (P < 0.001), but not tumor diameter, histology, or
      differentiation, further predicted survival. The median survivals for R0-resected
      intrahepatic, perihilar, and distal tumors were 80, 30, and 25 months,
      respectively, and the 5-year survivals were 63%, 30%, and 27%, respectively.
      CONCLUSION: R0 resection remains the best chance for long-term survival, and
      lymph node status is the most important prognostic factor following R0 resection.

PMID- 17457169
TI  - Referral pattern and timing of repair are risk factors for complications after
      reconstructive surgery for bile duct injury.
AB  - BACKGROUND: The aim of the present study was to assess the role of the referral
      pattern and the timing of the surgical procedure on outcome after reconstructive
      surgery for bile duct injury (BDI). SUMMARY BACKGROUND DATA: BDI after
      laparoscopic cholecystectomy remains a major problem in current surgical
      practice. Controversy exists about the influence of previous interventions before
      referral and the timing of repair on outcome. METHODS: Of 500 patients referred
      to a tertiary center, 151 patients (30.2%) underwent reconstructive surgery for
      BDI. The influence of referral pattern was analyzed by defining patients as
      primary and secondary referred patients. The influence of timing of repair was
      investigated by categorizing 3 groups of patients: A, acute repair; B, delayed
      repair; and C, late repair. RESULTS: Hospital mortality was zero. Perioperative
      complications occurred in 29 patients (19.2%): in 26.4% in secondary referred
      patients and 7.9% in primary referred patients (P = 0.04). Perioperative
      complications occurred in group A in 33.3%, in group B in 15.6%, and in group C
      in 22.5% (P = 0.22). Postoperative strictures occurred significantly more often
      in patients operated in the acute phase (P < 0.01) and in secondary referred
      patients (P = 0.03). A multivariate analysis identified 3 independent negative
      predictive factors for outcome: extended injury in the biliary tree (odds ratio =
      3.70; confidence interval, 1.32-10.34), secondary referral (odds ratio = 4.35;
      confidence interval, 1.12-16.76), and repair in the acute phase after injury
      (odds ratio = 5.44; confidence interval, 1.2-24.43). CONCLUSIONS: Reconstructive
      surgery for the treatment of BDI is associated with acceptable morbidity and no
      mortality. Extended injury to the bile duct, referral to a tertiary center after
      therapeutic interventions, and acute repair are independent negative predictors
      on outcome after reconstructive surgery for BDI.

PMID- 17457170
TI  - Hepatic resection but not radiofrequency ablation results in tumor growth and
      increased growth factor expression.
AB  - OBJECTIVE: The purpose of this study was to examine the effects of radiofrequency
      ablation (RFA) on tumor growth and growth factor expression in a murine model.
      BACKGROUND: Surgical excision remains the only potentially curative therapy for
      hepatic malignancies. Tumor growth in the remaining liver may be accelerated
      after resection. The mechanism of this enhanced tumor growth remains unexplained,
      although growth factors that are released after hepatic resection (which
      facilitate liver regeneration) may play a role in residual tumor growth. RFA has
      become a viable alternative for patients who are not candidates for a curative
      resection. The effect of RFA on tumor growth and growth factor expression has not
      been studied. METHODS: Hepatic tumors were established by direct injection with
      CT-26, a murine adenocarcinoma. Tumors were treated by either partial hepatic
      resection (PH) or RFA. Hepatocyte growth factor (HGF) and basic fibroblast growth
      factor (bFGF) expression was measured at selected time intervals post-treatment.
      Tumor growth was measured by reinjection of CT-26 into the residual liver after
      treatment. Nine days after reinjection, tumor volume was calculated and compared
      with nontreated controls. RESULTS: HGF and bFGF expression was significantly
      higher at baseline in the CT-26 tumor-bearing mice when compared with non-tumor
      bearing controls (P = 0.00001 and P = 9 x 10, respectively). There was an
      increase in HGF and bFGF expression at 24 hours (P = 0.005, and P = 0.001) in the
      PH group. In the RFA group, there was a decrease in HGF and bFGF expression at 24
      and 72 hours (P = 0.001 and P = 0.002). Tumor growth comparisons revealed an
      increase in tumor growth in the hepatectomy group (P = 0.006) but not the RFA
      group (P = 0.2). CONCLUSIONS: Baseline growth factor expression in tumor-bearing
      mice is exponentially higher when compared with non-tumor-bearing controls. HGF
      and bFGF expression are increased posthepatectomy, and decreased post-RFA.
      Partial hepatectomy results in an increase in tumor growth in the residual liver.
      RFA did not increase tumor growth after treatment. While hepatectomy is the only
      curative option for patients with hepatic malignancies, it may accelerate growth
      of microscopic residual disease.

PMID- 17457171
TI  - Hospital volume and late survival after cancer surgery.
AB  - CONTEXT: Although hospital procedure volume is clearly related to operative
      mortality with many cancer procedures, its effect on late survival is not well
      characterized. OBJECTIVE: To examine relationships between hospital volume and
      late survival after different types of cancer resections. DESIGN: Using the
      national Surveillance Epidemiology and End Results (SEER)-Medicare linked
      database (1992-2002), we identified all patients undergoing major resections for
      lung, esophageal, gastric, pancreatic, colon, and bladder cancer (n = 64,047).
      Relationships between hospital volume and survival were assessed using Cox
      proportional hazards models, adjusting for patient characteristics and use of
      adjuvant radiation and chemotherapy. STUDY PARTICIPANTS: U.S. Medicare patients
      residing in SEER regions. MAIN OUTCOME MEASURES: 5-year survival. RESULTS:
      Although there were statistically significant relationships between hospital
      volume and 5-year survival with all 6 cancer types, the relative importance of
      volume varied markedly. Absolute differences in 5-year survival probabilities
      rates between low-volume hospitals (LVHs) and high-volume hospitals (HVHs) ranged
      from 17% for esophageal cancer resection (17% vs. 34%, respectively) to only 3%
      for colon cancer resection (45% vs. 48%). Absolute differences in 5-year survival
      between LVHs and HVHs fell between these ranges for lung (6%), gastric (6%),
      pancreatic (5%), and bladder cancer (4%). Volume-related differences in late
      survival could not be attributed to differences in rates of adjuvant therapy.
      CONCLUSIONS: Along with lower operative mortality, HVHs have better late survival
      rates with selected cancer resections than their lower-volume counterparts.
      Mechanisms underlying their better outcomes and thus opportunities for
      improvement remain to be identified.

PMID- 17457172
TI  - Primary breast lymphoma: the role of mastectomy and the importance of lymph node
      status.
AB  - OBJECTIVE: To construct and analyze a database comprised of all reported cases of
      primary breast lymphoma (PBL) that include treatment and follow-up information
      published during the last 3 decades. SUMMARY BACKGROUND DATA: PBL accounts for
      0.4% of breast malignancies and 2% of extranodal lymphomas. Surgical therapy has
      varied from biopsy to radical mastectomy. Chemotherapy and radiation therapy have
      been used as adjuvant or primary therapy. A standard consensus treatment of PBL
      is not available. METHODS: We reviewed all published PBL reports from June 1972
      to March 2005. A database was compiled by abstracting individual patient
      information, limiting our study to those reports that contained specific
      treatment and outcome data. Patient demographics such as survival, recurrence,
      and time to follow-up were recorded, in addition to surgical, radiation, and/or
      chemotherapy treatment(s). RESULTS: We found 465 acceptable patients reported in
      92 publications. Age range was 17 to 95 years (mean, 54 years). Mean tumor size
      was 3.5 cm. Diffuse large cell (B) lymphoma was the most common histologic
      diagnosis (53%). Disease-free survival was 44.5% overall. Follow-up ranged from
      one to 288 months (mean, 48 months). Treatment by mastectomy offered no survival
      benefit or protection from recurrence. Treatment that included radiation therapy
      in stage I patients (node negative) showed benefit in both survival and
      recurrence rates. Treatment that included chemotherapy in stage II patients (node
      positive) showed benefit in both survival and recurrence rates. Histologic tumor
      grade predicted survival. CONCLUSIONS: Mastectomy offers no benefit in the
      treatment of PBL. Nodal status predicts outcome and guides optimal use of
      radiation and chemotherapy.

PMID- 17457173
TI  - Improved quality of life after bilateral laparoscopic adrenalectomy for Cushing's
      disease: a 10-year experience.
AB  - OBJECTIVE: To determine long-term quality of life after bilateral adrenalectomy
      for persistent Cushing's disease after transsphenoidal pituitary tumor resection.
      SUMMARY BACKGROUND DATA: Bilateral adrenalectomy for symptomatic relief of
      persistent hypercortisolism appears to be an effective treatment option. However,
      few studies have examined long-term outcomes in this patient population. METHODS:
      Retrospective review of 39 patients treated by bilateral laparoscopic
      adrenalectomy for Cushing's disease from 1994 to 2004. Patients completed a
      follow-up phone survey, including our Cushing-specific questionnaire and the SF
      12v2 health survey. Patients then refrained from taking their steroid replacement
      for 24 hours, and serum cortisol and ACTH levels were measured. RESULTS: Three
      patients died at 12, 19, and 50 months following surgery from causes unrelated to
      adrenalectomy. The remaining 36 patients all responded to the study questionnaire
      (100% response rate). Patients were between 3 months and 10 years post
      adrenalectomy. We had zero operative mortalities and a 10.3% morbidity rate. Our
      incidence of Nelson's syndrome requiring clinical intervention was 8.3%; 89% of
      patients reported an improvement in their Cushing-related symptoms, and 91.7%
      would undergo the same treatment again. Twenty of 36 (55%) and 29 of 36 (81%)
      patients fell within the top two thirds of the national average for physical and
      mental composite scores, respectively, on the SF-12v2 survey. An undetectable
      serum cortisol level was found in 79.4% of patients. CONCLUSIONS: Laparoscopic
      bilateral adrenalectomy for symptomatic Cushing's disease is a safe and effective
      treatment option. The majority of patients experience considerable improvement in
      their Cushing's disease symptoms, and their quality of life equals that of
      patients initially cured by transsphenoidal pituitary tumor resection.

PMID- 17457174
TI  - Exposure to bacterial DNA before hemorrhagic shock strongly aggravates systemic
      inflammation and gut barrier loss via an IFN-gamma-dependent route.
AB  - OBJECTIVE: To investigate the role of bacterial DNA in development of an
      excessive inflammatory response and loss of gut barrier loss following systemic
      hypotension. SUMMARY BACKGROUND DATA: Bacterial infection may contribute to
      development of inflammatory complications following major surgery; however, the
      pathogenesis is not clear. A common denominator of bacterial infection is
      bacterial DNA characterized by unmethylated CpG motifs. Recently, it has been
      shown that bacterial DNA or synthetic oligodeoxynucleotides containing
      unmethylated CpG motifs (CpG-ODN) are immunostimulatory leading to release of
      inflammatory mediators. METHODS: Rats were exposed to CpG-ODN prior to a
      nonlethal hemorrhagic shock. The role of interferon-gamma (IFN-gamma) was
      investigated by administration of anti IFN-gamma antibodies. RESULTS: Exposure to
      CpG-ODN prior to hemorrhagic shock significantly augmented shock-induced release
      of IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) (P < 0.05), interleukin
      (IL)-6 (P < 0.05), and nitrite levels (P < 0.05), while there was a defective IL
      10 response (P < 0.05). Simultaneously, expression of Toll-like receptor (TLR) 4
      in the liver was markedly enhanced. Furthermore, intestinal permeability for HRP
      significantly increased and bacterial translocation was enhanced in hemorrhagic
      shock rats pretreated with CpG-ODN. Interestingly, inhibition of IFN-gamma in CpG
      treated animals reduced TNF-alpha (P < 0.05), IL-6 (P < 0.05), nitrite (P <
      0.05), and intestinal permeability following hemorrhagic shock (P < 0.05) and
      down-regulated expression of TLR4. CONCLUSION: Exposure to bacterial DNA strongly
      aggravates the inflammatory response, disrupts the intestinal barrier, and up
      regulates TLR4 expression in the liver following hemorrhagic shock. These effects
      are mediated via an IFN-gamma-dependent route. In the clinical setting, bacterial
      DNA may be important in development of inflammatory complications in surgical
      patients with bacterial infection.

PMID- 17457175
TI  - Trauma-related infections in battlefield casualties from Iraq.
AB  - OBJECTIVE: To describe risks for, and microbiology and antimicrobial resistance
      patterns of, war trauma associated infections from Operation Iraqi Freedom.
      BACKGROUND: : The invasion of Iraq resulted in casualties from high-velocity
      gunshot, shrapnel, and blunt trauma injuries as well as burns. Infectious
      complications of these unique war trauma injuries have not been described since
      the 1970s. METHODS: Retrospective record review of all trauma casualties 5 to 65
      years of age evacuated from the Iraqi theatre to U.S. Navy hospital ship, USNS
      Comfort, March to May 2003.War trauma-associated infection was defined by
      positive culture from a wound or sterile body fluid (ie, blood, cerebrospinal
      fluid) and at least two of the following infection-associated signs/symptoms:
      fever, dehiscence, foul smell, peri-wound erythema, hypotension, and
      leukocytosis. A comparison of mechanisms of injury, demographics, and clinical
      variables was done using multivariate analysis. RESULTS: Of 211 patients, 56 met
      criteria for infection. Infections were more common in blast injuries, soft
      tissue injuries, >3 wound sites, loss of limb, abdominal trauma, and higher
      Injury Severity Score (ISS). Wound infections accounted for 84% of cases,
      followed by bloodstream infections (38%). Infected were more likely to have had
      fever prior to arrival, and had higher probability of ICU admission and more
      surgical procedures. Acinetobacter species (36%) were the predominant organisms
      followed by Escherichia coli and Pseudomonas species (14% each). CONCLUSIONS:
      Similar to the Vietnam War experience, gram-negative rods, particularly
      Acinetobacter species, accounted for the majority of wound infections cared for
      on USNS Comfort during Operation Iraqi Freedom. Multidrug resistance was common,
      with the exception of the carbapenem class, limiting antibiotic therapy options.

PMID- 17457176
TI  - Acute traumatic coagulopathy: initiated by hypoperfusion: modulated through the
      protein C pathway?
AB  - OBJECTIVES: Coagulopathy following major trauma is conventionally attributed to
      activation and consumption of coagulation factors. Recent studies have identified
      an acute coagulopathy present on admission that is independent of injury
      severity. We hypothesized that early coagulopathy is due to tissue hypoperfusion,
      and investigated derangements in coagulation associated with this. METHODS: This
      was a prospective cohort study of major trauma patients admitted to a single
      trauma center. Blood was drawn within 10 minutes of arrival for analysis of
      partial thromboplastin and prothrombin times, prothrombin fragments 1+2,
      fibrinogen, thrombomodulin, protein C, plasminogen activator inhibitor-1, and D
      dimers. Base deficit (BD) was used as a measure of tissue hypoperfusion. RESULTS:
      A total of 208 patients were enrolled. Patients without tissue hypoperfusion were
      not coagulopathic, irrespective of the amount of thrombin generated. Prolongation
      of the partial thromboplastin and prothrombin times was only observed with an
      increased BD. An increasing BD was associated with high soluble thrombomodulin
      and low protein C levels. Low protein C levels were associated with prolongation
      of the partial thromboplastin and prothrombin times and hyperfibrinolysis with
      low levels of plasminogen activator inhibitor-1 and high D-dimer levels. High
      thrombomodulin and low protein C levels were significantly associated with
      increased mortality, blood transfusion requirements, acute renal injury, and
      reduced ventilator-free days. CONCLUSIONS: Early traumatic coagulopathy occurs
      only in the presence of tissue hypoperfusion and appears to occur without
      significant consumption of coagulation factors. Alterations in the thrombomodulin
      protein C pathway are consistent with activated protein C activation and systemic
      anticoagulation. Admission plasma thrombomodulin and protein C levels are
      predictive of clinical outcomes following major trauma.

PMID- 17457177
TI  - In situ cross-linkable hyaluronan hydrogels containing polymeric nanoparticles
      for preventing postsurgical adhesions.
AB  - OBJECTIVE: To develop a combined barrier method and drug delivery system ("hybrid
      system") for preventing postoperative peritoneal adhesions, which could combine
      the biocompatibility and ease of application of in situ cross-linkable hydrogels
      with the controlled release features of polymeric nanoparticles. METHODS:
      Poly(lactic-co-glycolic acid) nanoparticles were dispersed in aldehyde- and
      hydrazide-modified hyaluronic acids (HA), then combined via a double-barreled
      syringe. The material was subjected to mechanical testing and was assayed for in
      vitro cytotoxicity to murine mesothelial cells. Subsequently, it was tested for
      biocompatibility by intraperitoneal injection in mice. The hybrid's effectiveness
      in preventing postsurgical adhesions was assessed using a rabbit sidewall defect
      cecum abrasion model, where it was applied to both injured surfaces. RESULTS: The
      in situ hybrid gel system formed a flexible and durable hydrogel in less than 10
      seconds. It had low in vitro cytotoxicity. In the mouse, the cross-linked HA
      maintained the polymeric nanoparticles in the peritoneum for 1 week, which we had
      previously shown would have cleared in less than 2 days, and no animals developed
      adhesions. Notably, the hybrid gel, even in the absence of encapsulated drug, was
      highly effective in preventing peritoneal adhesions in the rabbit model employed.
      Animals treated with the hybrid (n = 8) had no adhesions in 62.5% of cases, and
      none had adhesions that could only be separated by sharp dissection. In contrast,
      only 4.2% of untreated animals (n = 24) had no adhesions, and 58.3% developed
      adhesions requiring sharp dissection. CONCLUSIONS: The hybrid cross-linked HA
      nanoparticle system described here appears to be a biocompatible and highly
      effective adhesion barrier, which could also deliver antiadhesion drugs.

PMID- 17457179
TI  - A selective approach to resection of cystic lesions of the pancreas: results from
      539 consecutive patients.

PMID- 17457180
TI  - A selective approach to the resection of cystic lesions of the pancreas: results
      from 539 consecutive patients.

PMID- 17457182
TI  - Authors' response to a letter to the editor re: Sentinel node biopsy for early
      stage melanoma.

PMID- 17457183
TI  - Safety of UVA-riboflavin cross-linking of the cornea.
AB  - PURPOSE: To study potential damage to ocular tissue during corneal collagen cross
      linking (X-linking) by means of the riboflavin/UVA (370 nm) approach. METHODS:
      Comparison of the currently used technique with officially accepted guidelines
      regarding direct UV damage and the damage created by the induced free radicals
      (photochemical damage). RESULTS: The currently used UVA radiant exposure of 5.4
      mJ/cm and the corresponding irradiance of 3 mW/cm2 is below the known damage
      thresholds of UVA for the corneal endothelium, lens, and retina. Regarding the
      photochemical damage caused by the free radicals, the damage thresholds for
      keratocytes and endothelial cells are 0.45 and 0.35 mW/cm, respectively. In a 400
      microm-thick cornea saturated with riboflavin, the irradiance at the endothelial
      level was 0.18 mW/cm, which is a factor of 2 smaller than the damage threshold.
      CONCLUSIONS: After corneal X-linking, the stroma is depopulated of keratocytes
      approximately 300 microm deep. Repopulation of this area takes up to 6 months. As
      long as the cornea treated has a minimum thickness of 400 microm (as
      recommended), the corneal endothelium will not experience damage, nor will deeper
      structures such as lens and retina. The light source should provide a homogenous
      irradiance, avoiding hot spots.

PMID- 17457184
TI  - Treatment of progressive keratoconus by riboflavin-UVA-induced cross-linking of
      corneal collagen: ultrastructural analysis by Heidelberg Retinal Tomograph II in
      vivo confocal microscopy in humans.
AB  - PURPOSE: To assess ultrastructural stromal modifications after riboflavin-UVA
      induced cross-linking of corneal collagen in patients with progressive
      keratoconus. METHODS: This was a second-phase prospective nonrandomized open
      study in 10 patients with progressive keratoconus treated by riboflavin-UVA
      induced cross-linking of corneal collagen and assessed by means of Heidelberg
      Retinal Tomograph II Rostock Corneal Module (HRT II-RCM) in vivo confocal
      microscopy. The eye in the worst clinical condition was treated for each patient.
      Treatment under topical anesthesia included corneal deepithelization (9-mm
      diameter) and instillation of 0.1% riboflavin phosphate-20% dextran T 500
      solution at 5 minutes before UVA irradiation and every 5 minutes for a total of
      30 minutes. UVA irradiation was 7 mm in diameter. Patients were assessed by HRT
      II-RCM confocal microscopy in vivo at 1, 3, and 6 months after treatment.
      RESULTS: Rarefaction of keratocytes in the anterior and intermediate stroma,
      associated with stromal edema, was observed immediately after treatment. The
      observation at 3 months after the operation detected keratocyte repopulation in
      the central treated area, whereas the edema had disappeared. Cell density
      increased progressively over the postoperative period. At approximately 6 months,
      keratocyte repopulation was complete, accompanied by increased density of stromal
      fibers. No endothelial damage was observed at any time. CONCLUSIONS: Reduction in
      anterior and intermediate stromal keratocytes followed by gradual repopulation
      has been confirmed directly in vivo in humans by HRT II-RCM confocal microscopy
      after riboflavin-UVA-induced corneal collagen cross-linking.

PMID- 17457185
TI  - Efficacy of intracameral amphotericin B injection in the management of refractory
      keratomycosis and endophthalmitis.
AB  - PURPOSE: To evaluate the efficacy of intracameral amphotericin B injection in the
      adjunctive management of keratomycosis with probable intraocular extension not
      responding to conventional antifungal therapy. METHODS: Fourteen eyes of 12
      patients with fungal keratitis that did not respond to initial treatment with
      topical and intravenous fluconazole and oral itraconazole were treated with up to
      5 intracameral injections of 5 microg of amphotericin B. Six eyes received one
      injection, and 8 required subsequent injections. RESULTS: Twelve eyes responded
      to amphotericin B therapy, including 5 that healed with a central corneal scar
      and 8 that healed with a peripheral opacity. Two eyes progressed to evisceration.
      Four eyes developed anterior subcapsular cataract after intracameral amphotericin
      B. CONCLUSIONS: Intracameral amphotericin B may be an effective adjunctive
      treatment of fungal keratitis unresponsive to conventional antifungal therapy,
      although cataract may occur.

PMID- 17457186
TI  - Quantitative evaluation of tear meniscus height from fluorescein photographs.
AB  - PURPOSE: To describe a method of quantifying the tear meniscus height (TMH) and
      using these values to diagnose patients with dry eye. METHODS: Thirty-eight eyes
      of 19 healthy subjects and 14 patients diagnosed with dry eye were studied. Each
      eye received 2 microL of 1% fluorescein-sodium solution in the conjunctival sac,
      and digital photographs were taken of the external surface of the eye with a
      fundus camera. The tear meniscus was extracted from the digitalized image and
      used to measure the TMH with NIH image software. The correlation between the mean
      TMH and Schirmer test values or cotton-thread test values was evaluated. RESULTS:
      The means of the upper and lower TMH in healthy subjects were 0.22 +/- 0.06 and
      0.24 +/- 0.08 mm, respectively. The comparable values in patients with dry eye
      were 0.17 +/- 0.04 and 0.17 +/- 0.07 mm (upper TMS, P = 0.01; lower TMH, P =
      0.04; unpaired t test). A significant correlation was found between the TMH and
      Schirmer test values (r = 0.72, P = 0.01) but not with cotton-thread test values.
      CONCLUSIONS: Fluorescein photographs of the eye can be used to quantify the upper
      and lower TMH separately and simultaneously without specialized equipment. This
      technique can be used for the diagnosis of dry eye.

PMID- 17457187
TI  - Comparison of conjunctival autograft with amniotic membrane transplantation for
      pterygium surgery: surgical and cosmetic outcome.
AB  - PURPOSE: To compare the clinical results of conjunctival autograft and amniotic
      membrane transplantation (AMT) for primary and recurrent pterygium excision. In
      an effort to determine whether AMT yields acceptable cosmetic results as
      conjunctival autografting in pterygium surgery, we compared the final cosmetic
      outcomes of these 2 techniques. METHODS: We performed a prospective, randomized
      clinical study of 78 eyes (78 patients) divided into 2 groups. Forty eyes (28
      with primary and 12 with recurrent pterygia) received conjunctival limbal
      autograft (group 1), and 38 eyes (27 with primary and 11 with recurrent pterygia)
      received AMT (group 2) after extensive removal of pterygium. Mean follow-up time
      was 16.6 +/- 3.52 months in group 1 and 13.4 +/- 2.08 months in group 2. The
      results were evaluated by clinical examination and photographing and final
      appearances were graded from 1 to 4. Grade 4 represented true recurrence, whereas
      grade 3 indicated unacceptable cosmetic appearance. RESULTS: Recurrence rates of
      primary, recurrent, and all pterygia in group 1 and group 2 were 3.6%, 16.7%, and
      7.5% and 3.7%, 18.2%, and 7.9%, respectively. There was no significant difference
      in recurrence rates between the 2 groups (P = 1.00 for all). The rates of final
      appearance as grade 3 were 10.0% in group 1 and 21.1% in group 2, and the
      difference was statistically significant (P = 0.048). No major complications
      occurred during the follow-up period. CONCLUSIONS: Although better results in the
      final appearance were achieved using conjunctival autografting than with AMT, AMT
      can be a useful alternative in pterygium surgery, especially in those patients
      who may have a limited amount of conjunctiva for future surgeries.

PMID- 17457188
TI  - Elliptical nonmechanical corneal trephination: intraoperative complications and
      long-term outcome of 42 consecutive excimer laser penetrating keratoplasties.
AB  - PURPOSE: To assess intraoperative complications and long-term outcome of
      elliptical excimer laser trephination for penetrating keratoplasties (EELPKs)
      performed at the Friedrich-Alexander University of Erlangen, between 1989 and
      2002. METHODS: This was a retrospective, longitudinal, single-center, clinical,
      interventional case series. Forty-two eyes (14 Fuchs dystrophy, 11 corneal ulcer,
      7 aphakic/pseudophakic bullous keratopathy, 9 corneal scars, 1 keratotorus) after
      EELPK were observed. Trephination was performed with a 193-nm Meditec excimer
      laser along metal masks with 0-8 orientation teeth/notches. Horizontal/vertical
      graft diameters ranged from 7.0/6.0 to 8.0/7.0 mm, and 12 to 24 interrupted
      sutures were used. Simultaneously, 11 eyes (26.2%) underwent cataract surgery, 3
      (7.1%) underwent intraocular lens (IOL) exchange, and 1 (2.4%) underwent
      secondary IOL implantation. The main outcome measures included intraoperative
      complications, immune reactions, and final astigmatism/visual acuity at the end
      of follow-up. RESULTS: During surgery, 4 (9.5%) recipients had iris bleedings,
      and 10 (23.8%) ring-shaped superficial corneal thermal donor damages were
      detected. One (2.4%) immunologic graft rejection was seen in Fuchs dystrophy, and
      3 (7.1%) in corneal ulcers occurred during follow-up (4.7 +/- 3.2 years). At the
      end of follow-up, corrected visual acuity (0.1/0.4; P < 0.001) and keratometric
      astigmatism (2.3 D/4.7 D, P = 0.001) increased significantly. CONCLUSIONS: In
      EELPK, intraoperative disadvantages, such as the need for interrupted sutures and
      a tendency toward higher and more irregular astigmatism, may be expected. This
      study does not have the power to statistically confirm the tendency of EELPK
      toward a lower rate of immunologic graft rejections after normal-risk
      keratoplasty. However, EELPK may have advantages in deep or perforated
      elliptically shaped corneal ulcers (such as in acanthamoeba keratitis).

PMID- 17457189
TI  - Central corneal thickness in individuals with intellectual disabilities.
AB  - PURPOSE: To assess central corneal thickness (CCT) values in individuals with
      intellectual disabilities (ID). METHODS: The study group was made up of 25
      participants with ID (mean age, 36.9 +/- 8.7 years). The control group was made
      up of 25 healthy individuals (mean age, 37.1 +/- 10.1 years) with normal
      intellectual capacity and without any systemic or intraocular pathology. CCT
      value was measured by ultrasound pachymetry. Ten consecutive measurements were
      made at the center of the cornea of each eye. RESULTS: In the ID group, mean CCT
      value was 554.0 +/- 39.7 microm in the right eye and 556.8 +/- 38.7 microm in the
      left eye. In the control group, mean CCT value was 535.7 +/- 24.2 microm in the
      right eye and 536.5 +/- 24.8 microm in the left eye. CCT value in the ID group
      was significantly greater than in the control group for both right (P < 0.05) and
      left eyes (P < 0.02). CONCLUSIONS: CCT should be kept in mind during measurements
      of intraocular pressure (IOP) in individuals with ID because their CCTs may be
      greater than those in the general population.

PMID- 17457190
TI  - Supratarsal triamcinolone injection in the treatment of superior limbic
      keratoconjunctivitis.
AB  - PURPOSE: To evaluate the efficacy of supratarsal triamcinolone injection in the
      treatment of superior limbic keratoconjunctivitis (SLK). METHODS: Forty eyes of
      20 patients were diagnosed with SLK. All eyes with long-standing severe ocular
      irritation unresponsive to topical steroid and artificial tears were treated with
      supratarsal triamcinolone injection in addition to ongoing treatment of dry eye.
      Objective tarsal conjunctiva inflammation, bulbar conjunctiva, cornea staining,
      and subjective symptom gradings were performed before and after 2 weeks of
      therapy. All patients underwent laboratory evaluations of underlying systemic
      abnormalities. RESULTS: All 40 eyes responded well to treatment and had long-term
      (average, 7.8 months) improvement of irritation and dry sensation and improvement
      of inflammation and staining of conjunctiva and cornea. Fourteen patients (70%)
      had associated autoimmune diseases. There were no irreversible complications
      related to this therapy. CONCLUSIONS: Supratarsal triamcinolone injection
      effectively and rapidly resolved symptoms and signs associated with SLK. It is
      helpful as primary or adjunctive therapy for SLK.

PMID- 17457191
TI  - Rebound tonometer compared with goldmann tonometer in normal and pathologic
      corneas.
AB  - PURPOSE: To compare the intraocular pressure (IOP) measurements obtained with the
      rebound tonometer (RT) and the Goldmann handheld tonometer (GT) in normal and
      altered corneas. METHODS: A total of 208 normal corneas and 50 corneas with
      pathologies were included in this prospective study. All measurements were
      randomly obtained by 1 observer. The medians and interquartile range (IR) for
      both tonometers were compared. The median differences were assessed in IOP
      groups. Agreement between the tonometers was calculated using the Bland-Altman
      method. RESULTS: The median IOP in all eyes was 17 mm Hg (IR, 13-22 mm Hg) with
      the RT and 16 mm Hg (IR, 13-21 mm Hg) with the GT (P < 0.001). The correlation
      was excellent between tonometers (r2 = 0.86; P < 0.001). The minimal differences
      between the two were obtained from 10 to 20 mm Hg (GT). The Bland-Altman
      scatterplot obtained good agreement between the instruments. In normal corneas,
      the median difference was < or =2 mm Hg in 77.4% of cases. In the altered
      corneas, the median difference was < or =2 mm Hg in 73% of cases (P = 0.21
      compared with the normal group). In 10% and 2% of cases, the IOP could not be
      measured using the GT and RT, respectively. CONCLUSIONS: The results were similar
      for both tonometers. In the altered corneas, the IOP could be difficult to obtain
      with the GT because of distorted half-circles. The 1-mm-diameter disposable RT
      tip facilitated obtaining measurements without anesthetic drops, which avoids
      infections. The RT could be useful in routine clinical settings when measuring
      IOP in corneas with pathologies.

PMID- 17457192
TI  - Interleukin-6 and tumor necrosis factor-alpha levels in tears of patients with
      dry eye syndrome.
AB  - PURPOSE: To determine the levels of interleukin-6 (IL-6) and tumor necrosis
      factor-alpha (TNF-alpha) in tears of patients with dry eye syndrome. METHODS: IL
      6 and TNF-alpha levels were measured by enzyme-linked immunosorbent assay in tear
      samples obtained from 18 patients with dry eye (8 patients with Sjogren syndrome
      and 10 patients with non-Sjogren syndrome) and 14 control subjects. The
      correlation between IL-6 and TNF-alpha levels and tear film and ocular surface
      parameters was analyzed. The relative expression of these cytokines was evaluated
      in conjunctival impression cytology and conjunctival biopsy specimens by using
      immunohistochemical staining. RESULTS: The mean levels of IL-6 and TNF-alpha
      were, respectively, 18.57 +/- 8.92 and 3.68 +/- 3.45 pg/mL in patients with dry
      eye and 3.59 +/- 3.38 (P < 0.01) and < 0.5 (P < 0.01) pg/mL in control subjects.
      IL-6 level was significantly increased in tears of patients with Sjogren syndrome
      compared with those with non-Sjogren syndrome (P < 0.01). IL-6 level correlated
      significantly with tear film breakup time (P = 0.04), Schirmer test (P < 0.01),
      tear clearance (P = 0.02), keratoepithelioplasty score (P < 0.01), and goblet
      cell density (P = 0.03), but not with corneal sensitivity (P = 0.08). There was
      no significant difference in TNF-alpha level between patients with non-Sjogren
      and Sjogren syndrome. TNF-alpha levels did not correlate with tear film and
      ocular surface parameters. Immunohistochemical staining showed positive staining
      for IL-6 in specimens from patients with dry eye, especially in specimens from
      patients with Sjogren syndrome. CONCLUSION: IL-6 and TNF-alpha levels are
      elevated in tears of patients with dry eye syndrome. IL-6 level, but not TNF
      alpha level, is associated with the severity of the disease and correlates with
      various tear film and ocular surface parameters.

PMID- 17457193
TI  - Comparison of in vivo confocal microscopy of human cornea by white light scanning
      slit and laser scanning systems.
AB  - PURPOSE: To compare in vivo corneal imaging by scanning slit white light and
      laser confocal microscopy systems. METHODS: Twenty healthy individuals and 10
      patients with corneal dystrophies including Fuchs, granular, Map-Dot-Fingerprint
      dystrophies, and amiodarone-induced keratopathy were examined with the ConfoScan
      3 (Nidek Technologies) scanning slit white light confocal microscope equipped
      with x40 front lens (Zeiss) and the Rostock Cornea Module (RCM) for HRT II
      (Heidelberg Engineering) laser confocal microscopy system equipped with Olympus
      x60 front lens. The endothelial cell density counts were performed and results
      were compared. For additional validation of endothelial cells density results,
      separate counts were carried out using the specular microscope SP-1000 (Topcon).
      RESULTS: The healthy and pathologically changed corneal structures are imaged in
      a similar manner by both systems. The differences in quality of acquired images
      in contrast and brightness between the systems are debatable, although the laser
      system was more efficient for epithelium imaging and white light scanning slit
      was better for evaluation of endothelium. Some of the examinations completed with
      the laser system, which requires applanating its front lens to the cornea, imaged
      dark striae in posterior stroma and Descemet membrane folds, resembling those
      observed in corneal pathologies, whereas most were probably induced by the
      pressure applied to the cornea during examination. All the results of cell
      density (for patients and for subjects with no ophthalmic disease) counts
      performed with the RCM (laser system) were higher than those with the ConfoScan 3
      (scanning slit system) by 36.7% +/- 11.9% (SD) and 30.2% +/- 11.3% higher than SP
      1000 (specular). The difference in cell counts between the RCM and other methods
      was increasing at higher cell densities. CONCLUSIONS: The morphologic findings in
      examinations performed with the laser confocal microscopy system are generally
      comparable to white light scanning slit confocal microscopy. Direct applanation
      of the front lens of the laser system to the cornea may generate certain changes
      in confocal microscopy outcomes, including imaging of Descemet membrane folds and
      dark lines in stroma, which should be differentiated from pathologic alterations.
      Comparison of the endothelium cell density counts obtained with the 2 systems
      should be made cautiously because significant differences might occur--RCM
      configured with the Olympus x60 front lens was found to overestimate the results
      compared with both CS3 and SP-1000 microscopes, with the range of disparity
      increasing for higher cell densities.

PMID- 17457194
TI  - Comparative study of stromal bed quality by using mechanical, IntraLase
      femtosecond laser 15- and 30-kHz microkeratomes.
AB  - PURPOSE: To evaluate corneal stromal bed quality of lamellar keratectomy in laser
      in situ keratomileusis (LASIK) procedures by using mechanical and femtosecond
      laser microkeratomes. METHODS: LASIK corneal flaps were created in 9 fresh human
      globes not suitable for transplantation. We grouped the samples into 3 different
      groups of 3 globes each. Group 1 was the control group, in which the flaps were
      created using a Hansatome microkeratome with a 160-microm head. Groups 2 and 3
      consisted of flaps created at the 110-microm flap thickness setting using the
      IntraLase 15- and 30-kHz femtosecond laser, respectively. All the flaps were
      removed, and the corneal stromal beds were prepared for scanning electron
      microscopy (SEM). Qualitative surface roughness (QlSR) of the SEM images was
      graded using a roughness grading scale from 1 to 5 by 3 masked observers.
      Quantitative surface roughness (QnSR) of the SEM images was also assessed using
      software designed for roughness analysis. Mann-Whitney nonparametric statistical
      analysis was performed to compare groups. RESULTS: There was no statistically
      significant difference in QlSR and QnSR scores between group 2 and group 1 (brand
      new blade only). Group 3 30-kHz IntraLase samples showed a smoother stromal bed
      compared with group 1 and 2 samples. This was a statistically significant
      difference for QlSR (QlSR = 1.1 +/- 0.17, P < 0.001) and showed borderline
      significance for QnSR (QnSR = 24.4 +/- 0.96, P = 0.05). CONCLUSIONS: The
      IntraLase 15-kHz femtosecond laser 110-microm flaps and the Hansatome 160-microm
      head using a new blade both produced smooth, good-quality, compact stromal beds
      as assessed qualitatively by masked observers and quantitatively by image
      analysis software. The 30-kHz femotsecond laser permits a tighter spot/line
      separation and lower energy per pulse, which creates smoother corneal stromal
      beds.

PMID- 17457195
TI  - Hyperosmolarity-induced apoptosis in human corneal epithelial cells is mediated
      by cytochrome c and MAPK pathways.
AB  - PURPOSE: To study whether hyperosmolarity induces apoptosis in human corneal
      epithelial cells through cytochrome c-mediated death pathways and by activation
      of mitogen-activated protein kinases (MAPKs). METHODS: Primary human corneal
      epithelial cells cultured in normal osmolar media (312 mOsM) were switched to
      hyperosmolar media (450, 500, and 550 mOsM) by adding 70, 90, and 120 mM NaCl,
      respectively, with or without the c-jun N-terminal kinase (JNK) inhibitor
      SB202190 or the extracellular-regulated kinase (ERK) inhibitor PD98059. Apoptosis
      was assessed by the ApopTag In Situ Oligo Ligation (ISOL) assay. Confocal
      microscopy was used to detect cytochrome c and active caspase-3. Total RNA was
      extracted and subjected to reverse transcriptase-polymerase chain reaction for
      apoptosis-associated genes. Western blots were performed on cell extracts for the
      apoptogenic molecules cytochrome c and Smac/DIABLO, and phospho-JNK and ERK.
      RESULTS: ISOL-positive apoptotic cells significantly increased from 3.3 +/- 1.6%
      in control medium to 11.4 +/- 5.8%, 18.9 +/- 4.8%, and 43.9 +/- 8.8% in 70, 90,
      and 120 mM NaCl added media, respectively. The 90 mM NaCl high saline medium
      notably increased release of cytochrome c and Smac/DIABLO from mitochondria;
      activated caspase-3, JNK and ERK; stimulated mRNA expression of interleukin-1
      converting enzyme and Bax; and reduced Bcl2 expression. SB202190 and PD98059
      significantly suppressed hyperosmolarity-induced JNK/ERK activation and ISOL
      positive cells. In addition, PD98059 inhibited the release of cytochrome c and
      Smac/DIABLO from mitochondria. CONCLUSIONS: These findings show that
      hyperosmolarity induces apoptosis of human corneal epithelial cells through a
      cytochrome c-mediated death pathway, which may be mediated by JNK and ERK MAPK
      signaling pathways.

PMID- 17457196
TI  - Mitomycin-C concentration in cornea and aqueous humor and apoptosis in the stroma
      after topical mitomycin-C application: effects of mitomycin-C application time
      and concentration.
AB  - PURPOSE: To evaluate the effects of the applied mitomycin-C (MMC) concentration
      and application time on the aqueous MMC concentration and apoptosis in the
      corneal stroma. METHODS: New Zealand white rabbits underwent mechanical
      epithelium debridement of the central 7.5 mm of the cornea. A sponge soaked in
      MMC solution was placed on the denuded corneal stroma. The effect of the exposure
      times ranging from 15 to 120 seconds and the different MMC concentrations ranging
      from 0.005% to 0.04% on the aqueous MMC concentration and the apoptosis in the
      stromal cells were evaluated. RESULTS: The aqueous concentration of MMC increased
      linearly with increasing exposure time and MMC concentration. The correlation
      between the aqueous MMC concentration and the applied concentration (r = 0.809, P
      < 0.001) was higher than the correlation between the aqueous MMC concentration
      and the application time (r = 0.693, P < 0.001). Terminal
      deoxyribonucleotidyltransferase-mediated dUTP-digoxigenin nick end labeling
      (TUNEL)-positive cells were detected in the superficial stroma of the central
      denuded cornea. The numbers of TUNEL-positive cells increased linearly with
      increasing concentrations, and the increase was statistically significant (P =
      0.026). However, the numbers of TUNEL-positive cells increased only slightly with
      an increasing application time, and the increase was not statistically
      significant (P = 0.928). CONCLUSIONS: Reducing the applied concentration or
      decreasing the exposure time might be a good modality for reducing the potential
      MMC toxicity. The applied MMC concentration had greater effects on the aqueous
      MMC concentration and apoptosis in the stromal cells than the exposure time.

PMID- 17457197
TI  - MLH1 and MSH2 expression in pterygia.
AB  - PURPOSE: Pterygia have been reported to share some of the genetic defects seen in
      cancers, including microsatellite instability (MSI). We examined pterygia for the
      presence of proteins typically missing or defective in adenocarcinomas with MSI.
      We also performed microsatellite analysis on DNA from pterygia to test for
      instability in the size of the microsatellites, using markers conventionally used
      to characterize MSI in tumors (Bethesda convention markers). METHODS: We examined
      13 pterygia by immunohistochemistry for MLH1 and MSH2, 2 proteins involved in DNA
      mismatch repair. In addition, we amplified the pterygial DNA with primers
      specific for 5 Bethesda markers (BAT25, BAT26, D2S123, D5S346, and D17S250).
      RESULTS: MLH1 staining was present at low levels in the basal cells of the cornea
      and migrating limbal cells of the pterygia. MSH2 staining was present in basal
      and in maturing epithelial cells of the cornea and migrating limbal cells of
      pterygia. We observed no reproducible examples of MSI or loss of heterozygosity
      (LOH). CONCLUSIONS: We were unable to confirm the presence of MSI and LOH by
      using the markers we examined. MSH2 staining appeared to be normal in pterygia.
      MLH1 staining was present but in reduced amounts compared with that seen in the
      conjunctiva.

PMID- 17457198
TI  - Human anterior lens capsule as a biologic substrate for the ex vivo expansion of
      limbal stem cells in ocular surface reconstruction.
AB  - PURPOSE: To study the potential use of human anterior lens capsule as a scaffold
      for stem cell transplantation in treatment of limbal cell deficiency. METHODS:
      Limbal biopsies and anterior lens capsules were obtained (same eye) from 30
      patients during cataract surgery. Biopsies were suspended in Dulbecco modified
      Eagle medium under sterile conditions and stored at 4 degrees C. Capsules were
      treated in distilled water under strict asepsis for 2 hours to eliminate the
      crystalline epithelium and stored at 4 degrees C. After initial processing, the
      limbal biopsy was plated epithelial-side down (48 hours) on the capsular specimen
      in a 35-mm culture dish. Samples were sorted into 4 groups. Group 1 was made up
      of 10 samples in which limbal biopsies were allowed to grow on corresponding
      capsules from the same eye (autologous). Group 2 was 10 limbal biopsies that were
      allowed to grow on capsules of different eye (allogeneic). The remaining
      specimens were randomized into 2 groups. Group 3 included 10 capsules on which an
      ex vivo expanded cell line was allowed to grow. Group 4 harbored 10 limbal
      biopsies that were allowed to grow on polystyrene culture plates. All specimens
      were incubated for 2 weeks at 37 degrees C and 5% CO2. Cell density, viability,
      morphology, and adherence of the cell-capsule complex were evaluated at 1, 3, 7,
      and 14 days. RESULTS: Rate of cell growth and density in groups 1 and 2 were
      comparable to the control groups. Cell viability was 95% or superior in all
      groups, and desmosomes developed between growing cells. CONCLUSIONS: Human
      anterior lens capsule is a potential scaffold for ex vivo expansion of limbal
      epithelial cells, possibly providing a substrate for ocular surface
      reconstruction.

PMID- 17457199
TI  - Central corneal delle as a complication of erythema multiforme major.
AB  - PURPOSE: To report a case of erythema multiforme major complicated by a central
      corneal delle. METHODS: Case report. RESULTS: An 18-year-old man recovering from
      erythema multiforme major complained of blurred vision and grittiness. Slit-lamp
      examination revealed a central corneal depression; the overlying epithelium was
      intact, and the stroma was thinned but lacked inflammation. The patient underwent
      2 months of treatment with lubrication and autologous serum. The thinning corneal
      stroma thickened, and the corneal curvature returned to normal without any
      further complications such as corneal perforation. CONCLUSIONS: Erythema
      multiforme major caused upper tarsus deformity and dry eye, which resulted in
      localized corneal dehydration and a central corneal delle.

PMID- 17457200
TI  - Iris cavernous hemangioma associated with multiple cavernous hemangiomas in the
      kidney, brain, and skin.
AB  - PURPOSE: To document the relationship of iris cavernous hemangiomas with
      multiorgan hemangiomas in a child. METHODS: A 7-year-old girl with kidney
      hemangiomas, brain hemangiomas, and skin hemangiomas developed blurred vision and
      darkening of the right iris. She had undergone 6 previous brain surgeries and
      multiple revisions of a ventriculoperitoneal shunt for hydrocephalus beginning at
      age 3 months. RESULTS: Examination revealed visual acuity of 20/30 in the right
      eye and 20/20 in the left eye. There was a reddish-purple lobulated cystic mass
      along the superior iris pupillary margin measuring 2 mm in greatest diameter
      confirmed by ultrasound biomicroscopy. The remainder of the ocular examination
      was unremarkable. The diagnosis was iris cavernous hemangioma in a patient with
      multiorgan cavernous hemangiomatosis. By 1-year follow-up, the iris hemangioma
      deflated, leaving a fibrotic, involuted scar. CONCLUSIONS: Iris cavernous
      hemangioma can be associated with multiorgan hemangiomas that can be life
      threatening.

PMID- 17457201
TI  - Asymptomatic conjunctival mucosa-associated lymphoid tissue-type lymphoma with
      presumed intraocular involvement.
AB  - PURPOSE: To report a case of conjunctival mucosa-associated lymphoid tissue
      (MALT) lymphoma with presumed intraocular involvement. METHODS: Observational
      case report. RESULTS: A 73-year-old white man presented for a routine eye
      examination and was found to have a salmon-colored bulbar conjunctival mass of
      the left eye. Ultrasound showed a low-reflective mass with diffuse thickening of
      the ciliary body and choroid. Immunohistochemistry and flow cytometry of an
      incisional biopsy specimen suggested a polyclonal lesion. Treatment with topical
      steroids yielded no clinical improvement, and excisional biopsy was performed. A
      diagnosis of MALT lymphoma was made after polymerase chain reaction (PCR)
      analysis of the immunoglobulin heavy chain (IgH) locus revealed a clonal B-cell
      population. CONCLUSIONS: Conjunctival MALT lymphoma can present without symptoms
      and can extend intraocularly. PCR analysis of the IgH locus can identify lesion
      clonality when immunohistochemistry and flow cytometry fail to do so.

PMID- 17457202
TI  - Complete spontaneous crystalline lens dislocation into the anterior chamber with
      severe corneal endothelial cell loss.
AB  - PURPOSE: To report an unusual case of a spontaneously dislocated crystalline lens
      into the anterior chamber that was successfully treated. METHODS: A generally
      healthy 49-year-old woman with no history of trauma presented with a
      spontaneously dislocated crystalline lens into the anterior chamber accompanied
      by corneal endothelial cell loss. The crystalline lens was extracted
      intracapsularly after gentle separation from the corneal endothelium by using a
      viscoelastic material. RESULTS: Visual acuity remained at 20/16 from 1 day
      postoperatively, with little endothelial cell loss compared with preoperatively.
      CONCLUSIONS: A spontaneously dislocated crystalline lens into the anterior
      chamber with severe corneal endothelial cell loss was treated successfully by
      intracapsular extraction.

PMID- 17457203
TI  - Development of superior limbic keratoconjunctivitis after upper eyelid
      blepharoplasty surgery: support for the mechanical theory of its pathogenesis.
AB  - PURPOSE: To describe a unique presentation of superior limbic
      keratoconjunctivitis (SLK) that occurred after upper eyelid blepharoplasty and to
      review the literature regarding the current theories of SLK pathogenesis and its
      treatment. METHODS: A 48-year-old woman presented with a 2-year history of
      irritation and foreign body sensation in both eyes that began immediately after
      bilateral upper eyelid blepharoplasty. Her symptoms were unresponsive to therapy
      with lubricating eyedrops and ointments, cyclosporine 0.05% drops, and silver
      nitrate cauterization. The patient subsequently underwent surgical resection of
      the superior bulbar conjunctiva in both eyes. RESULTS: Complete resolution of SLK
      symptoms. CONCLUSIONS: The pathogenesis of SLK has been associated with
      mechanical injury to the superior limbus and superior bulbar conjunctiva. The
      development of SLK after upper eyelid blepharoplasty in our patient supports this
      theory and should be considered a possible adverse consequence of blepharoplasty.

PMID- 17457204
TI  - Descemet stripping with endothelial keratoplasty for treatment of iridocorneal
      endothelial syndrome.
AB  - PURPOSE: To describe use of Descemet stripping with endothelial keratoplasty
      (DSEK) to treat corneal edema associated with iridocorneal endothelial (ICE)
      syndrome. METHODS: In this retrospective, consecutive, interventional case
      series, the corneal endothelium was selectively replaced by the DSEK technique in
      eyes with ICE syndrome. Three eyes were treated at 1 center between June 2005 and
      July 2006. Descemet membrane and endothelium were stripped from the recipient and
      an 8- or 8.5-mm-diameter donor button consisting of posterior stroma and healthy
      endothelium was folded and implanted through a 5-mm incision. An air bubble was
      used to press the donor tissue against the recipient cornea, allowing it to
      attach without sutures. In 1 case with extensive peripheral anterior synechiae
      (PAS), after the PAS were broken, the anterior chamber was shallow, so a
      temporary anchor suture was placed in the peripheral edge of the donor tissue to
      help ensure that it would unfold in the correct orientation. RESULTS: DSEK
      successfully resolved corneal edema in 3 male patients with unilateral ICE
      syndrome who were 47 to 67 years of age. Follow-up ranged from 1 to 14 months.
      Best spectacle-corrected visual acuity at the most recent visit was 20/20 to
      20/30, with a mean refractive cylinder of 1.2 D. CONCLUSIONS: Selective
      replacement of dysfunctional endothelium with DSEK can successfully treat corneal
      edema and associated visual loss and pain caused by ICE syndrome. Visual recovery
      is rapid and refractive changes are minimal compared with replacement of the full
      corneal thickness with a traditional penetrating keratoplasty.

PMID- 17457205
TI  - Topical steroids in the management of Churg-Strauss syndrome involving the
      conjunctiva.
AB  - PURPOSE: To discuss a case of Churg-Strauss syndrome that developed bilateral
      conjunctival involvement while recovering from miliary tuberculosis. METHODS:
      Case report and literature review. RESULTS: A 22-year-old man who was on oral
      prednisolone for Churg-Strauss syndrome since 2002 contracted miliary
      tuberculosis in June 2004. The diagnosis was confirmed by liver biopsy.
      Ophthalmologic examination was within reference limits except for bilateral
      multifocal choroiditis. A combined therapy of rifampicin, ethambutol,
      streptomycin, and morphazinamide was started on June 24, 2004. Complete recovery
      was achieved, and the antituberculosis therapy was terminated in June 2005. The
      patient noted redness and pain in both eyes a month later. He had bilateral
      irregular, pink-yellow, gravel-like infiltrations involving the bulbar
      conjunctiva. Biopsy revealed granulomas with central fibrinoid necrosis,
      histiocytes, and eosinophils, suggestive of conjunctival involvement of Churg
      Strauss syndrome. Topical dexamethasone 0.1% drops were started 4 times per day
      and tapered gradually. Lesions totally regressed within 2 months. No recurrence
      was noted during a follow-up of 11 months. CONCLUSIONS: Churg-Strauss syndrome
      may rarely involve the conjunctiva, and conjunctival lesions respond favorably to
      topical steroids.

PMID- 17457206
TI  - In vivo confocal microscopy of subepithelial infiltrates in human corneal
      transplant rejection.
AB  - PURPOSE: Corneal allograft rejection is the leading cause of penetrating
      keratoplasty failure in the first year after surgery. We report 2 cases of
      subepithelial infiltrates in corneal transplant rejection imaged by in vivo
      confocal microscopy. METHODS: Case report and review of relevant literature.
      RESULTS: Two subjects with subepithelial infiltrates in previously clear
      penetrating corneal transplants were assessed. In vivo confocal microscopy
      revealed focal accumulations of hyperreflective dendritic-like particles,
      postulated to represent Langerhans cells, at the level of the basal epithelium
      and Bowman membrane. Altered keratocytes with visible cytoplasmic processes were
      observed posterior to these foci. CONCLUSIONS: To our knowledge, these are the
      first reported cases of in vivo confocal microscopy appearance of corneal
      allograft rejection in humans. In vivo confocal microscopy may provide a valuable
      clinical tool to aid in the diagnosis of early corneal transplant rejection and
      in the differential diagnosis of other inflammatory conditions of the cornea.

PMID- 17457207
TI  - Unilateral lacrimal gland atrophy in a patient with hereditary angioedema.
AB  - PURPOSE: To report a case of unilateral lacrimal gland atrophy in a patient with
      hereditary angioedema (HAE). METHODS: Observational case report with literature
      review. RESULTS: A 32-year-old woman with HAE presented with dryness and
      irritation of the left eye (OS). Investigations revealed features of unilateral
      severe dry OS with atrophy of the ipsilateral lacrimal gland confirmed by
      magnetic resonance imaging (MRI). CONCLUSIONS: Dry eye should be included in the
      ocular manifestations of HAE. Recurrent mucosal and soft-tissue inflammation
      secondary to HAE may lead to lacrimal gland atrophy. MRI is a useful, noninvasive
      tool in diagnosing lacrimal gland atrophy.

PMID- 17457208
TI  - Deep anterior lamellar keratoplasty for post-LASIK ectasia.
AB  - PURPOSE: To describe 2 cases of post-laser in situ keratomileusis (LASIK) ectasia
      managed with deep anterior lamellar keratoplasty (DALK). METHODS: Clinical
      findings, surgical interventions, and outcomes are reported. The surgical
      technique of DALK is described. RESULTS: Two patients developed progressive loss
      of vision after LASIK surgery with enhancement procedure(s). Corneal ectasia was
      diagnosed on the basis of clinical findings, progressive central corneal thinning
      on pachymetry, and topographical changes with irregular astigmatism and inferior
      corneal steepening. Both patients underwent uneventful DALK surgery, in which the
      anterior 80% of the central corneal stroma was replaced by a donor button and
      sutured in place. The postoperative recovery was uneventful, except for mild
      interface haze in 1 case, which resolved within 2 weeks of surgery. However, 1
      patient underwent additional surgery, including clear lens extraction with
      intraocular lens placement, astigmatic keratotomies, and photorefractive
      keratectomy (PRK) to achieve good unaided visual acuity. At last follow-up, at
      least 2 years after DALK, both patients were satisfied with their vision. Their
      uncorrected visual acuity (UCVA) was 20/60+ and 20/40- in their operated eyes,
      improving to 20/40+ and 20/30- with minimal refractive corrections. The grafts
      and lamellar interfaces were clear. CONCLUSIONS: We believe that DALK should be
      considered as an alternative to penetrating keratoplasty for the surgical
      management of post-LASIK ectasia.

PMID- 17457209
TI  - Long-term follow-up of free-floating epithelial inclusion cyst after radial
      keratotomy.
AB  - PURPOSE: To report the benign seven year follow-up on a free-floating anterior
      chamber epithelial inclusion cyst that did not require treatment. DESIGN:
      Retrospective observational case report. METHODS: Seven years of clinical
      observation of a patient who had radial keratotomy in 1998. RESULTS: The free
      floating cyst showed no growth or untoward effects on the eye and required no
      treatment during the observation period. CONCLUSIONS: The long clinical course of
      our patient shows that epithelial inclusion cysts may be managed without
      treatment for many years with careful and frequent follow-up.

PMID- 17457211
TI  - Efficient activation of autologous tumor-specific T cells: a simple coculture
      technique of autologous dendritic cells compared to established cell fusion
      strategies in primary human colorectal carcinoma.
AB  - Different technologies have been employed to deliver the whole spectrum of tumor
      antigens (TAs) to dendritic cells (DCs) to be presented to T cells. These include
      whole tumor RNA-transfected DCs, preparations of DCs loaded with tumor-derived
      apoptotic bodies or tumor cell lysates, and DC tumor cell fusions. Early clinical
      trials have been conducted using such techniques. The presented study was aimed
      to revisit the necessity of tumor cell manipulation in DC-based immunotherapy
      strategies for colorectal carcinoma. We investigated a simple coculture method of
      autologous monocyte-derived DCs and human primary colorectal carcinoma (pCC) in
      comparison with 2 well-described cell fusion strategies for the efficacy of
      uptake, processing and presentation of TAs to autologous T cells. Before
      coculture or fusion, pCC had been cryopreserved without further manipulation.
      Fluorescence microscopy and flow cytometry analyses of fluorescent dye labeled
      cells were used for monitoring engulfment of pCC by DCs. The coculture procedure
      resulted in a double positive cell fraction of up to 22% and thus was comparable
      to that observed after cell fusion. More important, DCs after coculture with
      autologous pCC induced significant tumor-specific interferon-gamma-producing
      autologous T cells in the same number of patients as DC/pCC fusions. Furthermore,
      tumor-specific major histocompatibility complex class I restricted cytotoxic T
      lymphocytes were generated by stimulation with DCs cocultured with pCC. In prior
      studies for human carcinomas coculture techniques were described to be inferior.
      In contrast, our data strongly suggest that at least for human pCC and autologous
      DCs this simple coculture method is similarly efficient compared to established
      fusion techniques.

PMID- 17457212
TI  - Zoledronic acid has direct antiproliferative and antimetastatic effect on
      pancreatic carcinoma cells and acts as an antigen for delta2 gamma/delta T cells.
AB  - Beside their use as antiresorptive drug, bisphosphonates are well known to
      stimulate gammadelta T cells and to have direct effects on tumor growth. We
      determined the direct cytotoxic potential, induction of apoptosis, and
      antimigratory effect of zoledronic acid. The susceptibility of pancreatic
      carcinoma cells pretreated with bisphosphonates against gammadelta T cells was
      tested and the subgroup involved in killing was determined. Zoledronic acid has a
      cytotoxic potential even at pharmacologic dosage. Zoledronic acid does not only
      induce apoptosis by inhibiting the Ras-pathway but has also an antimetastatic
      effect as shown in migration assays and by down-regulation of urokinase
      plasminogen activator. Freshly prepared gammadelta T cells consisting mainly of
      Vdelta2 cells showed increased cytotoxicity against bisphosphonate-treated
      pancreatic carcinoma cells. Our results demonstrate that zoledronic acid has a
      direct apoptotic effect on pancreatic carcinoma cells and has antimigratory
      properties. Tumor cells treated with zoledronic acid are more vulnerable against
      Vgamma9 Vdelta2 T cell attack. Treatment with zoledronic acid for patients with
      pancreatic carcinoma might be an option.

PMID- 17457213
TI  - "Pathogen-mimicking" nanoparticles for vaccine delivery to dendritic cells.
AB  - A clinically relevant delivery system that can efficiently target and deliver
      antigens and adjuvant to dendritic cells (DCs) is under active investigation.
      Immunization with antigens and immunomodulators encapsulated in poly(D,L-lactic
      co-glycolic acid) (PLGA) nanoparticles elicits potent cellular immune responses;
      but understanding how this mode of delivery affects DCs and priming of naive T
      cells needs further investigation. In the current study, we assessed the extent
      of maturation of DCs after treatment with monophosphoryl lipid A (MPLA)
      encapsulated in PLGA nanoparticles and the generation of primary T-cell immune
      responses elicited by DCs loaded with antigens using this approach. Results
      indicated that DCs up-regulated the expression of surface maturation markers and
      demonstrated an enhanced allostimulatory capacity after treatment with MPLA
      containing PLGA nanoparticles. Treatment of DCs with MPLA containing
      nanoparticles released high amounts of proinflammatory and TH1 (T helper 1)
      polarizing cytokines and chemokines greater than that achieved by MPLA in
      solution. The delivery of ovalbumin in PLGA nanoparticles to DCs induced potent
      in vitro and in vivo antigen-specific primary TH1 immune responses that were
      furthermore enhanced with codelivery of MPLA along with the antigen in the
      nanoparticle formulation. Delivery of MUC1 lipopeptide (BLP25, a cancer vaccine
      candidate) and MPLA in PLGA nanoparticles to human DCs induced proliferation of
      MUC1 reactive T cells in vitro demonstrating the break in tolerance to self
      antigen MUC1. These results demonstrated that targeting antigens along with toll
      like receptor ligands in PLGA nanoparticles to DCs is a promising approach for
      generating potent TH1 polarizing immune responses that can potentially override
      self-tolerance mechanisms and become beneficial in the immunotherapy of cancer
      and infectious diseases.

PMID- 17457214
TI  - Targeting, imaging, and therapy using a humanized antiprostate stem cell antigen
      (PSCA) antibody.
AB  - The murine 1G8 (micro1G8) monoclonal antibody directed against prostate stem cell
      antigen (PSCA) prevents prostate tumor establishment, growth, and metastasis in
      murine models. To further delineate in vivo targeting properties, micro1G8 was
      radiolabeled with In-111 and evaluated in nude mice bearing PC3-PSCA xenografts.
      Tumor activity ranged from 11.8% to 17.1% injected dose per gram (ID/g) at 24 to
      96 hours postinjection. To extend the clinical applicability of micro1G8, a
      chimeric 1G8 antibody was produced that exhibited specific binding to PSCA and
      significant antitumor effect over micro1G8 in established LAPC-9 prostate cancer
      xenografts (P=0.0014). However, low expression yields and instability prompted us
      to humanize 1G8 by grafting the complementary determining regions onto the
      stable, human Fv framework of anti-p185 4D5v8 (trastuzumab). Two humanized 1G8
      (hu1G8) versions (A and B) that differed in the number of murine residues present
      in the C-terminal half of CDR-H2, were produced. Biacore binding studies
      demonstrated affinities of 1.47 nM for micro1G8 and 3.74 nM for hu2B3-B,
      representing a 2.5-fold reduction. Tumor targeting of version B radioiodinated
      with I was evaluated by serial microPET imaging. Specific tumor targeting of I
      hu1G8-B to PC3-PSCA [12.7 (+/-1.6)% ID/g at 94 h] and LAPC-9 [6.6 (+/-0.9)% ID/g
      at 168 h) xenografts was observed. Inhibition of tumor growth by hu1G8-B was
      demonstrated in mice bearing low-expressing SW-780-PSCA bladder carcinoma
      xenografts. In this model, the micro1G8 was ineffective, whereas the hu1G8-B
      exhibited approximately 50% inhibitory effect. These data support further
      development of hu1G8 anti-PSCA antibody for targeted imaging and therapy for
      tumors of urogenital origin.

PMID- 17457215
TI  - 4-1BB costimulation of effector T cells for adoptive immunotherapy of cancer:
      involvement of Bcl gene family members.
AB  - We previously reported that in vitro costimulation of murine MCA 205 tumor
      draining lymph node (TDLN) cells through a third signal, 4-1BB (CD137), in
      addition to CD3 and CD28 engagement significantly increases T-cell yield and
      amplifies antitumor responses in adoptive therapy. The increased T-cell yield
      seemed to be related to inhibition of activation-induced cell death. In this
      study, using real time-polymerase chain reaction and intracellular staining, we
      tested our hypothesis that antiapoptotic Bcl gene members are modulated in 4-1BB
      ligated TDLN cells. TDLN cells activated through 4-1BB in conjunction with
      CD3/CD28 demonstrated elevated Bcl-2 and Bcl-xL gene and protein expression
      compared with CD3/CD28 activation. Furthermore, Bcl-2 and/or Bcl-xL inhibition
      abrogated 4-1BB-conferred rescue of activation-induced cell death in TDLN cells,
      and as a result, 4-1BB-enhanced TDLN cell yield was abolished. Congenic mice were
      used as donors for TDLN cells labeled with CFSE to evaluate proliferation and
      persistence of activated cells after intravenous adoptive transfer. The effector
      function of transferred cells was assessed by determining the incidence of
      interferon-gamma-producing cells in response to tumor stimulation in serial blood
      samples drawn from treated mice using intracellular cytokine staining. CD28 and
      CD28/4-1BB costimulation significantly enhanced in vivo proliferation and
      survival of the infused cells compared with CD3 activation. 4-1BB coligation
      augmented the proliferation and effector function of the infused cells compared
      with both CD3 and CD3/CD28-activated cells. Characterizing the function of
      signaling molecules involved in T-cell activation pathways may allow optimization
      of conditions in the generation of effector T cells for cancer immunotherapy.

PMID- 17457216
TI  - Expression of CXCR3 on mononuclear cells and CXCR3 ligands in patients with
      metastatic renal cell carcinoma in response to systemic IL-2 therapy.
AB  - Chemokines play an important role in regulating tumor-mediated immunity,
      angiogenesis, and tumor cell metastasis. The chemokine receptor, CXCR3, is
      expressed in various human tumors, including renal cell carcinoma (RCC). CXCR3 is
      also associated with antiangiogenic effects in multiple tumors, and we
      hypothesized that interleukin-2 (IL-2) treatment of patients with metastatic
      clear cell RCC could augment CXCR3 levels on circulating mononuclear cells and
      correlate to outcome. The kinetics of CXCR3 expression on circulating mononuclear
      cells and its ligands (CXCL9, CXCL10, and CXCL11) in plasma were evaluated in 20
      patients with metastatic clear cell RCC during cycles 1 and 2 of high dose IL-2
      therapy. Subpopulations of peripheral blood mononuclear cells (PBMCs) were
      studied by dual color flow cytometry. Angiogenic ligands were measured and an
      "angiogenic ratio" was calculated prehigh and posthigh dose IL-2. CXCR3
      expression on PBMC at baseline was similar in patients with metastatic RCC and
      normal controls. PBMC CXCR3 expression increased during treatment, and peaked
      during cycle 2. Plasma from RCC patients displayed similar baseline levels of
      CXCR3 ligands to normal controls. However, the angiogenic ratio was significantly
      increased in patients with metastatic RCC at baseline. Plasma levels of CXCR3
      ligands increased during treatment, resulting in a reversal in the angiogenic
      ratio to favor angiostatic chemokines. The CXCR3/CXCR3 ligand biologic axis and
      angiogenic ratio may be important biomarkers in clear cell RCC patients who are
      undergoing high dose IL-2 therapy.

PMID- 17457219
TI  - Multicenter phase II study of chemo-immunotherapy in the treatment of metastatic
      renal cell carcinoma.
AB  - The purpose of this study was to evaluate the potential efficacy of a chemo
      immunotherapy regimen for the treatment of metastatic renal cell carcinoma
      (MRCC). Forty-one patients with progressing MRCC and with a median age of 63
      years were recruited. Planned treatment consisted of 6 courses of capecitabine
      1000 mg/m twice daily on days 1 to 14 every 4 weeks, pegylated alpha-interferon
      2b 50 microg every week, interleukin-2 1.8 M IU subcutaneously, and oral 13-cis
      retinoic acid 0.5 mg/kg, all given 5 days/wk, 3 weeks of each month. After 6
      courses of concomitant biochemotherapy, biotherapy was continued in patients who
      had a clinical benefit. The primary end point was response; secondary end points
      were the evaluation of the immunologic parameters, toxicity, progression-free,
      and overall survival. The treatment was well-tolerated. Grade 3 and 4 neutropenia
      and thrombocytopenia occurred in 5% and 7% of patients, respectively. The overall
      response rate in the 41 evaluable patients was 53.6% (95% confidence interval 37%
      69%). Median progression-free and overall survivals were 14.7 and 27.8 months,
      respectively. A sustained improvement in all evaluated immunologic parameters was
      observed in the 36 patients treated with maintenance biotherapy. Six cycles of
      biochemotherapy, being followed by maintenance immunotherapy is well-tolerated
      and shows significant activity in patients with MRCC.

PMID- 17457217
TI  - AFP-specific CD4+ helper T-cell responses in healthy donors and HCC patients.
AB  - Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and
      is often diagnosed at an advanced stage. We have investigated alpha-fetoprotein
      (AFP) as a tumor-associated antigen for HCC. We identified major
      histocompatibility complex class I-restricted peptide epitopes derived from AFP
      and studied CD8 T-cell responses in vivo and in vitro in ongoing immunotherapy
      studies. Helper T cells are of critical importance in shaping the immune
      response; therefore, we investigated the frequency and function of AFP-specific
      CD4 T cells in the general population and among HCC patients. CD4 T-cell
      responses were assessed by direct ex vivo multicytokine enzyme-linked immunospot
      assay and by measurement of cytokine levels using a multicytokine assay. Our
      analysis indicates that healthy donors have very low frequencies of AFP-specific
      CD4 T-cell responses, which are of TH1 type, detectable ex vivo. In contrast,
      these T cells were either reduced or eliminated in HCC patients at advanced
      stages of disease. To better activate these cells, we compared the stimulatory
      capacity of both AFP protein-fed and AdVhAFP-engineered dendritic cells (DC).
      Healthy donors have CD4 T-cell responses, which were activated in response to AFP
      protein-fed DC whereas HCC patients do not demonstrate significant responses to
      AFP protein. AdVhAFP-transduced DC were capable of activating higher frequency
      TH1 CD4 responses to AFP in both healthy donors and AFP-positive HCC patients.
      Importantly, CD4 T-cell cytokine expression profiles were skewed towards
      interleukin-2 and interferon-gamma production when activated by adenovirally
      engineered DC, which has therapeutic implications for vaccination efforts.

PMID- 17457218
TI  - Inability to mediate prolonged reduction of regulatory T Cells after transfer of
      autologous CD25-depleted PBMC and interleukin-2 after lymphodepleting
      chemotherapy.
AB  - CD25CD4 regulatory T cells (Treg) regulate peripheral self-tolerance and possess
      the ability to suppress antitumor responses, which may explain the poor clinical
      response of cancer patients undergoing active immunization protocols, and
      provides the rationale for neutralizing Treg cells in vivo to strengthen local
      antitumor immune responses. Because interleukin-2 (IL-2) mediates tumor
      regression in about 15% of treated patients but simultaneously increases Treg
      cells, we hypothesized that transient elimination of Treg cells will enhance the
      clinical effectiveness of IL-2 therapy. In the current study, 5 patients with
      metastatic melanoma who were refractory to prior IL-2 received a lymphodepleting
      preparative regimen followed by the adoptive transfer of autologous lymphocytes
      depleted of CD25 Treg cells and high-dose IL-2 administration. CD25 cells were
      eliminated from patient leukapheresis samples using a clinical-grade, large-scale
      immunomagnetic system, leaving CD8 and CD25CD4 T cells intact. In the early
      aftermath of CD25 Treg cell-depleted cell infusion, CD25FOXP3+ CD4 Treg cells
      rapidly repopulated the peripheral blood of treated patients with 18% to 63% of
      CD4 T cells expressing FOXP3. Recovering CD25CD4 T cells exhibited suppressive
      activity against CD25CD4 effector T-cell proliferation in vitro. No patient
      experienced objective tumor regression or autoimmunity. Our results indicate that
      in vivo transfer of autologous CD25-depleted mononuclear populations to
      lymphopenic patients in combination with high-dose IL-2 is not sufficient to
      mediate prolonged reduction of Treg cells after IL-2 administration.

PMID- 17457220
TI  - Induction of adaptive Anti-HER2/neu immune responses in a Phase 1B/2 trial of 2B1
      bispecific murine monoclonal antibody in metastatic breast cancer (E3194): a
      trial coordinated by the Eastern Cooperative Oncology Group.
AB  - 2B1 is a bispecific murine monoclonal antibody that binds to the extracellular
      domains of HER2/neu and FcgammaRIII. 2B1 efficiently promotes the lysis of tumor
      cells overexpressing HER2/neu by natural killer cells and mononuclear phagocytes
      that express the FcgammaRIII A isoform. Here, we report the results of E3194, a
      phase 1B/2 trial conducted by the Eastern Cooperative Oncology Group that
      employed 2B1 therapy in 20 women with metastatic breast cancer. The median age
      was 51 years. All but 1 patient had received prior chemotherapy. After the first
      dose, 3 of the initial 8 patients experienced dose-limiting toxicities that
      required dose-reduction. The nature of these dose-limiting toxicities resulted in
      a reduced dose from 2.5 mg/m/d to 1 mg/m/d in the remaining 12 patients.
      Objective antitumor responses were not seen. However, 2B1 therapy induced
      adaptive immune responses to both intracellular and extracellular domains of
      HER2/neu. Even though 2B1 antibody therapy did not show activity in metastatic
      breast cancer at the current administered doses, the ability of this antibody to
      induce detectable immune responses against an important tumor antigen has
      implications for understanding the mechanisms by which antibodies that mediate
      antibody-directed cellular cytotoxicity may exert their clinical antitumor
      effects.

PMID- 17457222
TI  - Predictive factors for response and for resistance to tyrosine kinase inhibitor
      therapy in lung cancer.

PMID- 17457223
TI  - Gender differences: implications for clinical trials and practice.

PMID- 17457224
TI  - Combination of standard chemotherapy and targeted agents.

PMID- 17457225
TI  - Radiofrequency ablation of inoperable non-small cell lung cancer.

PMID- 17457226
TI  - Lung cancer.

PMID- 17457227
TI  - The role of pharmacogenetics in adjuvant treatment of non-small cell lung cancer.
AB  - The disappointing results of long-term survival among patients with non-small
      cell lung cancer (NSCLC) may reflect the lack of knowledge of the ways in which
      molecular abnormalities of neoplastic cells affect responsiveness to anticancer
      therapy. Remarkable advances in the understanding of NSCLC cancer biology have
      been made over the past decade, including the discovery of critical mutations in
      oncogenes (i.e., mutation of K-Ras and c-myc gene), as well as the loss of tumor
      suppressor genes, such as TP53, 16INK4, or Rb. The future challenge of NSCLC
      chemotherapy relies on the identification of molecular markers that are
      predictive of drug sensitivity and help in the selection of chemotherapeutic
      agents best suited to the individual patient. Other intriguing issues will be the
      identification of the optimal drug sequence in combination regimens, as well as
      polymorphisms of genes involved in severe toxicities.

PMID- 17457228
TI  - Role of induction chemotherapy in resectable N2 non-small cell lung cancer.

PMID- 17457229
TI  - Multimodality treatment of stage IIIA and IIIB non-small cell lung cancer.

PMID- 17457230
TI  - Sentinel lymph node mapping: detection of micrometastases by polymerase chain
      reaction in non-small cell lung cancer.

PMID- 17457231
TI  - Toward therapies tailored to patient characteristics.

PMID- 17457232
TI  - Combination of target agents: challenges and opportunities.

PMID- 17457233
TI  - Image-guided radiotherapy and hypofractionation in lung cancer.

PMID- 17457234
TI  - Observational, one-arm studies and randomized population-based trials for
      evaluation of the efficacy of lung cancer screening.

PMID- 17457235
TI  - Stereotactic body radiation therapy for early non-small cell lung cancer:
      experience at the University of Turin.

PMID- 17457236
TI  - Fluoro-2-deoxy-D-glucose positron emission tomography in lung cancer.

PMID- 17457237
TI  - Adjuvant chemotherapy for non-small cell lung cancer.
AB  - Cisplatin must be considered the treatment standard for lung cancer chemotherapy,
      whatever the disease setting, at least in the Western world. After the seminal
      meta-analysis published in 1995, 12 randomized clinical trials (RCTs) exploring
      the benefits of adjuvant cisplatin-based chemotherapy have been completed,
      published, or presented. Although all these RCTs differ in patient features, two
      common suggestions emerge when the stage is taken into account: a significant
      benefit for chemotherapy is demonstrated for stage II and IIIA patients and none
      of these trials showed any significant benefit for adjuvant chemotherapy in stage
      IB patients. Ten years after this meta-analysis, a further individual patient
      data-pooled analysis exploring the eventual benefits of adjuvant cisplatin-based
      chemotherapy after surgery for early stage non-small cell lung cancer in the more
      recent RCTs has been presented. The 5-year overall survival benefit in favor of
      cisplatin-based chemotherapy was 5.3% (48.8% versus 43.3%, p = 0.004), with a
      relative risk reduction of 11%. These results confirm those reported by previous
      meta-analyses performed according to a literature-based approach. Advances are
      emerging in the selection of those patients who are likely to benefit more from
      such treatment. In this respect, the customized therapy based on
      molecular/genetic patient and disease features constitutes a new avenue to
      pursue.

PMID- 17457238
TI  - Syphilis serologic prevalence monitoring among STD clinic clients: correlation
      with reported syphilis incidence, San Diego, CA, 1985-2004.
AB  - OBJECTIVE: To describe the serologic test for syphilis (STS) prevalence among STD
      clinic clients, determine the correlation between STS prevalence trends and
      reported community-diagnosed primary and secondary (P&S) case incidence, and
      evaluate the usefulness of STS prevalence monitoring as a component of syphilis
      surveillance. STUDY: During the period 1985-2004, 21,4336 STS were done among STD
      clinic clients and a variety of STS prevalence measures were evaluated. RESULTS:
      From 1985-1991, 10.2% of STS were positive, which declined to 5.6% during 1992
      2004. Overall, STS positivity (>or=1:8) and male positivity (>or=1:8) trends were
      correlated with reported community-diagnosed P&S case incidence and case
      incidence in men (r = 0.58 and r = 0.81, respectively). Male STS positivity
      (>or=1:8) began increasing in 2001, 1 year before the increase in syphilis
      incidence in men, which began in the latter half of 2002 and occurred mostly
      among men who have sex with men. CONCLUSION: In a syphilis outbreak in men who
      have sex with men, STS prevalence (>or=1:8) among male STD clinic clients was a
      useful measure of syphilis case incidence trends and may provide an early warning
      for a subsequent increase in community-diagnosed case incidence.

PMID- 17457239
TI  - Performance of focus ELISA tests for HSV-1 and HSV-2 antibodies among university
      students with no history of genital herpes.
AB  - OBJECTIVES: To define the performance characteristics of the Focus ELISA HSV-1
      and HSV-2 assay among 100 university students. STUDY DESIGN: HSV-1 and HSV-2
      Focus ELISA and Western Blot assays were performed on sera from university
      students who reported no history of genital herpes. RESULTS: HSV-2 and HSV-1
      seroprevalence by Western Blot were 3.4% and 48%, respectively. In this
      population, the positive predictive value of the Focus HSV-2 ELISA was 37.5%, the
      sensitivity was 100%, and specificity was 94.1%. The PPV of the Focus HSV-1 ELISA
      was 96.7%, the sensitivity was 69.0%, and the specificity was 97.8%. CONCLUSIONS:
      In this low-prevalence population, the positive predictive value of the Focus HSV
      2 ELISA test was low. This finding, together with those reported elsewhere,
      indicates that caution is warranted when recommending HSV screening in low
      prevalence or heterogeneous populations. Consideration should be given to raising
      the cutoff index value for defining a positive test result.

PMID- 17457240
TI  - Sexually transmitted infections in men in Mumbai slum communities: the
      relationship of prevalence to risk behavior.
AB  - OBJECTIVES: The objectives of this study were to identify sexually transmitted
      infection (STI) prevalence, assess behavioral and symptom correlates, and develop
      intervention strategies. GOAL: The goal of this study was to conduct one of the
      first community-based surveys of STI prevalence and risk behaviors among married
      men in India. STUDY DESIGN: In 2003, 2,408 randomly selected married men, aged 21
      to 40 years, were administered a survey instrument with urine and blood samples
      collected from a random subset of 641. RESULTS: The most common current STI was
      gonorrhea (3.9%) with 6.1% of men being positive for an acute STI and 9.7%
      antibody-positive for Treponema pallidum or herpes simplex virus type 2. Risk
      behaviors were not associated with laboratory confirmed STIs, but did show an
      association with men's concerns about sexual performance derived from traditional
      Indian systems of medicine. CONCLUSION: Culturally based symptoms can serve as
      effective markers for men involved in risky sexual behaviors and provide an
      opportunity to engage these men as they seek care for these symptoms at community
      based service points.

PMID- 17457256
TI  - [Diffusion MRI: technique and clinical applications].
AB  - Diffusion MRI gives information that is not available with conventional MRI
      examinations. It can provide early diagnosis of stroke and helps in diagnosing
      cerebral lymphoma, cerebral bacterial abscess, and epidermoid cyst. It helps
      distinguish between vasogenic edema and cytotoxic edema and has prognostic value.
      Acquisition is fast and should be performed in all neuroradiological
      examinations.

PMID- 17457257
TI  - [MR and CT perfusion imaging of the brain: principles and clinical applications].
AB  - MR and CT imaging techniques provide both morphological data and functional data.
      MR and recently CT perfusion have substantially modified the treatment of acute
      stroke. CT perfusion offers new opportunities to improve the management strategy
      in vasospasm after subarachnoid hemorrhage. Both are also helpful for the
      diagnosis of brain tumors and the assessment of treatment effects.

PMID- 17457258
TI  - [Advanced vascular imaging techniques of supra-aortic, encephalic and medullary
      vessels].
AB  - Recent technical progress of MRI and CT made it possible to widen the field of
      exploration of the noninvasive vascular imaging in the study of supra-aortic,
      encephalic and medullary vessels. MRI of the carotid plaques, CT angiography in
      the detection of the intracranial aneurysms, intracranial time-resolved MRA and
      MRA of the spinal cord took their place in the field of the noninvasive vascular
      imaging.

PMID- 17457259
TI  - [Brain magnetic resonance spectroscopy].
AB  - MR spectroscopy (MRS) sequences allow noninvasive exploration of brain metabolism
      during a MRI examination. Their day-to-day use in a clinical setting has recently
      been improved by simple programming of sequences and automated quantification of
      metabolites. However, a few simple rules should be observed in the choice of
      sequences and the location of the voxels so as to obtain an informative, high
      quality examination. The research applications of MR spectroscopy, where use of
      this examination seeks to better understand the pathophysiology of the disease,
      must be distinguished from its clinical indications, where MRS provides
      information that can be used directly in patient management. The most significant
      of the clinical uses are imaging intracranial tumors (positive and differential
      diagnosis, extension, treatment follow-up), diffuse brain injury,
      encephalopathies (especially hepatic and HIV-related), and the diagnosis of
      metabolic disorders.

PMID- 17457260
TI  - [Functional magnetic resonance imaging: physiopathology, techniques and
      applications].
AB  - Brain functional MRI (fMRI) provides an indirect mapping of cerebral activity,
      based on the detection of local changes in blood flow and oxygenation levels that
      are associated with neuronal activity (BOLD contrast). fMRI allows noninvasive
      studies of normal and pathological aspects of the brain's functional
      organization. It is based on the comparison of two or more cognitive states.
      Echoplanar imaging is the technique of choice, providing the quickest study of
      the entire brain. Activation maps are calculated from a statistical analysis of
      the local signal changes. fMRI has become one of the most widely used functional
      imaging techniques in neuroscience. In clinical practice, fMRI can identify
      eloquent areas involved in motor and language functions in surgical patients and
      can evaluate the risk of postoperative neurological deficit.

PMID- 17457261
TI  - [Diffusion tensor imaging and tractography of the brain and spinal cord].
AB  - Diffusion tensor imaging is a magnetic resonance imaging technique that provides
      details on tissue microstructure and organization well beyond the usual image
      resolution. With diffusion tensor imaging, diffusion anisotropy can be quantified
      and subtle white matter changes not normally seen on conventional MRI can be
      detected. The aim of this article is to review the principles of diffusion tensor
      imaging and fiber tracking and their applications to the study of the brain,
      including Alzheimer disease, neuropsychiatric disorders, strokes, multiple
      sclerosis, brain tumors, and intractable seizures. Emerging applications to
      spinal cord disorders are also presented.

PMID- 17457263
TI  - [It's high time we spoke about doses! Or don't tell my mother I'm a radiologist.
      She reads "Le Point"].

PMID- 17457264
TI  - [Magnetic resonance imaging of angiogenesis in tumors].
AB  - Tumor angiogenesis induces the proliferation of immature blood vessels that are
      both heterogeneous and leaky. These characteristics can be demonstrated by
      measuring the perfusion parameters with MRI. Perfusion MRI is usually performed
      with in T1-weighted dynamic imaging after bolus injection of an exogenous
      contrast agent such as gadolinium chelate. The perfusion parameters are obtained
      by semi-quantitative or quantitative analysis of the enhancement curves in the
      tumor and the arterial input. Perfusion can also be assessed without injecting a
      contrast agent using arterial spin labeling techniques, diffusion MRI, or BOLD
      (blood oxygen level dependent) MRI. However, these latter methods are limited by
      a low signal-to-noise ratio and problems with quantification. The main indication
      for perfusion MRI is the assessment of antiangiogenic and antivascular
      treatments. New possibilities for demonstrating angiogenic blood vessels are
      being opened by molecular imaging.

PMID- 17457265
TI  - [Heart and heart-lung transplants thorax complications: major radiologic forms].
AB  - Bipulmonary and cardiopulmonary transplantations are among the most difficult to
      perform, with a 10-year survival rate estimated at 33%. This low rate can be
      attributed to thoracic complications that can be classified into three distinct
      groups: 1) early complications, occurring in the first 30 days after
      transplantation (hemothorax, diaphragmatic paralysis, reperfusion edema, hydric
      overloading, acute rejection); 2) late complications that occur beyond the first
      month (bronchiolitis obliterans syndrome, bronchic stenosis, sirolimus-induced
      lung disorders, initial disease recurrence); and 3) infections classed separately
      because of their high morbidity and mortality (thoracic wall abscess, bacterial
      and viral pneumonia, CMV, pneumocystosis, Aspergillus necrotizing bronchitis).
      Imaging is essential in screening and diagnosing these complications as part of
      the clinician's monitoring throughout the rest of the transplant recipient's
      life. In diagnosis, combined with clinical and biological data, imaging has its
      place in delaying the onset of these diseases.

PMID- 17457266
TI  - [Sonography of peripheral nerves. Part II: lower limbs].
AB  - On sonographic images, the peripheral nerves have a fibrillary structure,
      ribboned on longitudinal images and ovoid on cross-section images. The nerves
      travel between the muscle groups, often with blood vessels, or in canals.
      Recently improved ultrasound devices are able to investigate the peripheral
      nerves along their entire length, as far as the sonographer has thorough
      anatomical knowledge, rigorous technique, and, when searching for pathology, good
      clinical notions. As in Part I on sonography of the peripheral nerves of the
      upper limbs, published in this journal, the objective of this general review is
      to present normal and pathological echoanatomy of the peripheral nerves of the
      lower limbs in an educational way.

PMID- 17457267
TI  - [Radiography of scoliosis: comparative dosimetry between conventional technique
      and digital fluorography].
AB  - OBJECTIVE: Compare the irradiation delivered in conventional radiography and
      digital radiography by image intensifier during a scoliosis workup. PATIENTS AND
      METHODS: Our prospective randomized study included 105 patients, all of whom were
      identified according to sociodemographic parameters as well as criteria
      evaluating the quality of the full front spinal x-ray at PA incidence. The entry
      dose at the scapula and the exit dose in interorbital, thyroid, mammary, and
      hypogastric projection was measured by thermoluminescent dosimeters. RESULTS: The
      results of 71 girls and 28 boys, aged a mean 13.8 years with a mean weight of 47
      kg were analyzed. At equal image quality, the entry dose was not significantly
      different between the two techniques; the mean exit dose reduction was 64% during
      digital acquisition. This reduction involved the interorbital (162%), mammary
      (43%), and thyroid (309%) regions. However, this system is more irradiating in
      the hypogastric region (34%). CONCLUSION: The dosimetric evaluation of the
      different imaging techniques used to explore the entirety of the spine should be
      part of radiologists' quality standard used to document their work and their
      choices.

PMID- 17457268
TI  - [Embolization of localized pulmonary arteriovenous malformations in adults].
AB  - OBJECTIVES: To report our experience using embolization in managing localized
      pulmonary arteriovenous malformations in adults. MATERIAL: and methods. All
      patients presenting with localized pulmonary arteriovenous malformations treated
      with embolization were included in the study. Clinical presentation (respiratory
      symptoms and previous history of paradoxical embolism) and the characteristics of
      pulmonary arteriovenous malformations (single or multiple, location, diameter of
      the afferent artery and simple or complex angioarchitecture) before embolization
      were analyzed. The details of the procedure, including the number of pulmonary
      arteriovenous malformations embolized, the number of coils used, and the type of
      intraoperative complications were recorded. Postembolization clinical and imaging
      follow-up were described. RESULTS: Forty-two patients (26 women, 16 men; mean
      age, 45 years), including 36 with hereditary hemorrhagic telangiectasia were
      treated with embolization. Twenty-two patients (53%) were dyspneic and 12 (29%)
      had a previous history of paradoxical embolism prior to embolization. Forty-seven
      procedures were carried out on a total of 99 pulmonary arteriovenous
      malformations (mean, 2.3 per patient), using 530 coils (12.6 per patient). The
      pulmonary arteriovenous malformations were located in the lower lobes in 60% of
      cases and a simple architecture was reported in 81% of cases. The average
      diameter of the afferent artery was 6mm. No preoperative complications were
      reported. After embolization, two patients (5%) presented with a paradoxical
      embolism and five patients out of 22 (23%) remained dyspneic. The rate of
      complete occlusion of treated arteriovenous malformations was 92% using computer
      tomography. CONCLUSION: Embolization is a highly effective and safe technique for
      treating pulmonary arteriovenous malformations. Improvement in dyspnea and
      prevention of paradoxical embolism can be expected. A high technical success rate
      can be obtained by experienced interventional radiologists.

PMID- 17457269
TI  - [Benefit of hip ultrasound in management of the limping child].
AB  - OBJECTIVE: To evaluate the contribution of sonography of the hip in the
      management of nontraumatic limping in children. PATIENTS AND METHODS: Prospective
      study including children consulting for nontraumatic limping (n=93). These
      children had a clinical examination, a biological and imaging workup (pelvis x
      rays (n=88), initial sonograph of the hip (n=93), and follow-up sonograph of the
      hip (n=29)). RESULTS: Ninety-three children (69 boys, 24 girls) aged from 10
      months to 13 years (median, 4 years) were included and divided into two groups:
      The sensitivity and specificity of sonography in establishing a serious diagnosis
      was 57% and 59%, respectively. CONCLUSION: The advantage of systematic hip
      sonography is challenged in this study because of low sensitivity and
      specificity. Its main advantage seems to be in its negative results, which prompt
      other investigations.

PMID- 17457270
TI  - [What is the thickness of the normal appendix on MDCT?].
AB  - OBJECTIVE: To determine the wall thickness and external diameter values of the
      normal appendix on multidetector computed tomography (MDCT). Materials and
      methods. A senior radiologist with no knowledge of the patient's surgical history
      prospectively examined the abdominal-pelvic CT scans of 57 consecutive adult
      patients with no suspicion for appendicitis. Most of the patients (50/57)
      received an intravenous iodinated contrast material injection, but none had
      gastrointestinal studies. All slices (1 and 5 mm) and multiplanar reconstructions
      were analyzed on a treatment console. The external diameter of the appendix, the
      thickness of the two appendicular walls, and the presence or absence of
      intraluminal gas were noted. RESULTS: The appendix was visualized in 82% of the
      cases (47/57). The mean external diameter was 6.7 mm+/-1.2 (range, 5.0-11.0 mm).
      The mean thickness of the two walls was 4.8 mm+/-1.0 (range, 2.6-6.4 mm).
      Intraluminal air was visualized in 87% of cases (41/47). CONCLUSION: Contrary to
      external diameter, the normal thickness of the appendix's two walls does not go
      beyond the threshold of 6 mm and therefore seems to be a reliable measurement for
      identifying a normal appendix using MDCT.

PMID- 17457271
TI  - [Spontaneous pneumomediastinum and marijuana].

PMID- 17457272
TI  - [Colon CT exploration of an internal hernia of the ascending cecocolon through
      the hiatus of Winslow].

PMID- 17457273
TI  - [Melorheostosis: a radiological and clinical case report].

PMID- 17457274
TI  - [Extraosseous osteosarcoma in paratesticular location: case report].

PMID- 17457275
TI  - [MRI and CT without contrast material injection: which provides the best
      diagnosis for stroke?].

PMID- 17457276
TI  - [Number 2-2007 question answer. Diagnosis of omentum infarction].

PMID- 17457277
TI  - [What is your diagnosis?].

PMID- 17457278
TI  - [Including exposure dose in radiological reports: how? why?].

PMID- 17457279
TI  - [15th Consensus Conference on anti-infectious treatments: management of viral
      infections of the lower respiratory tract in the immunocompetent adult. Short
      text].

PMID- 17457280
TI  - [New biological treatments for lung cancer].
AB  - Therapies targeted on cell signal pathways that control cell division and tumor
      angiogenesis have been developed over the last five years for non small cell lung
      cancer (NSCLC) with some amazing results, in subgroups of selected patients,
      predicting more significant success in the upcoming years. Compounds targeted on
      EGF tyrosine kinase receptor have been tested in large clinical phase 2 and 3
      trials including thousands of patients. Their efficacy has been proved, in second
      and third line trials, after first line cisplatin-based chemotherapy for non
      mucinous adenocarcinoma in non-smokers, women and Asian patients. Response rates
      vary from 10% in non selected Caucasian patients to 40% in non-smoking Asian
      patients with long survivals. Therapeutic targeting improves success rates,
      either relying on EGFR gene amplification detection by FISH, or search for EGFR
      tyrosine kinase domain mutations. Commercial kits are available for routine
      molecular diagnosis of domain mutations potentially enabling molecular targeting
      in addition to clinical targeting. Angiogenesis inhibitors, especially monoclonal
      antibody to VEGF, bevacizumab, have also been developed in the last few years.
      Bevacizumab associated with classical cytotoxic chemotherapy led, in selected
      patients (with non squamous cell lung cancer and no past history of
      cardiovascular disease) to an increase of median survival to more than 12 months
      with tolerable toxicity. Other drugs that have both anti-EGFR activity and anti
      angiogenic properties will be soon developed, since future bioactive anti-cancer
      drugs will probably be multi-targeted drugs.

PMID- 17457281
TI  - [Prognosis of mucoepidermoid carcinoma of the bronchi].
AB  - BACKGROUND: Mucoepidermoid cancer is exceptional in the respiratory tract,
      accounting for only 0.2% of primary lung cancers. CASE REPORTS: We report three
      cases of mucoepidermoid carcinoma. The inaugural signs were hemoptysia in a 10
      year-old child, recurrent lower respiratory tract infections in a 13-year-old
      child, and dyspnea with chest pain in a 32-year-old adult. Bronchial fibroscopy
      disclosed a proximal endobronchial tumor in all three patients. Pathology study
      of the operative specimen identified low-grade malignant mucoepidermoid carcinoma
      in the two children and high-grade malignant mucoepidermoid carcinoma in the
      adult. Surgical resection was performed for the pediatric cases. Outcome was
      favorable with recurrence-free survival at eight years in the first child. The
      surgical resection was less radical in the second child due to locoregional
      extension. This child was lost to follow-up. The clinical course was rapidly
      fatal in the third patient who presented metastatic spread at diagnosis and died
      one month later. DISCUSSION: The prognosis of mucoepidermoid tumors of the
      bronchi is closely related to tumor grade and extension at diagnosis. Unlike high
      grade mucoepidermoid carcinoma, the progression of low-grade tumors, which
      predominate in children, is generally slow, enabling good prognosis if diagnosis
      is established early. Early search for these tumors in patients presenting
      chronic or recurrent respiratory manifestations would avoid late diagnosis and
      improve prognosis.

PMID- 17457282
TI  - [Smoking in school: Cocody, Abidjan].
AB  - MATERIAL AND METHODS: A cross-sectional study on smoking in school was conducted
      in public, private, and international secondary schools in Cocody, Abidjan,
      between March 18 and May 4, 2003. Data were collected with an anonymous
      individual questionnaire from 1000 pupils. RESULTS: Pupils smoked for the first
      time at an early age, 13.9 years on average. The prevalence of smoking was 15.9%,
      with a strong proportion of girls who smoked (10.6%). Smoking was particularly
      prevalent in private and international schools. Many pupils (37.7%) stated their
      teachers also smoked in the school and in their presence. Only 13.8% of parents
      knew their children smoked. Favoring factors observed were the influence of
      smoking parents (26.5%), influence of smoking peers (67.6%). Two motivations were
      predominant: curiosity and imitation. Most pupils bought their cigarettes with
      their pocket money (62.7%). Most smokers smoked in night clubs and bars (74.3%)
      and drank alcohol (69%). Less than two-thirds of the pupils were knowledgeable
      about the consequences of smoking: basically they knew about lung diseases
      (62.9%), and particularly lung cancer (63% of lung diseases). The majority of the
      pupils were aware of the nicotine content of cigarettes (52.8%).

PMID- 17457283
TI  - [Audit of management of chronic obstructive pulmonary disease by general
      practitioner in Morrocco].
AB  - OBJECTIVE: The purpose of this study initiated in January 2003 was to evaluate
      the awareness of general practitioners in Morrocco concerning the diagnosis and
      initial management of chronic obstructive pulmonary disease (COPD). METHOD AND
      RESULTS: Ten percent of the COPD patients, selected at random, participated in
      the study, i.e; 223 patients/2186. The proportion of COPD patients among patients
      attending consultations was 5 to 10% for 40% of general practitioners. Only 48.9%
      of the general practitioners were aware of international guidelines for the
      management of COPD. For 97.8%, chronic bronchial symptoms were the predominant
      reasons for suspecting the diagnosis of COPD; other symptoms included exercise
      induced dyspnea (95.1%). Only 10.8% of the general practitioners ordered a
      spirometry examination. Only 30.5% managed patients themselves. CONCLUSION: Our
      findings show that general practitioners should be implicated in the diagnosis
      and early management of COPD but that management practices could be improved.

PMID- 17457284
TI  - [Filling the thymic space after treatment of Hodgkin's disease: rebound or
      relapse].
AB  - We report the case of a 36-year-old women with Hodgkin's disease treated with
      polychemotherapy and bone marrow autograft. Progressive growth of a thymic mass
      suggested possible relapse four months after treatment withdrawal. This mass did
      not exhibit gallium-67 uptake but showed strong affinity for 18-FDG (SUV=6.8).
      Surgical biopsy ruled out recurrence of Hodgkin's disease of the thymus and led
      to the diagnosis of thymic rebound. The aspect of the thymic compartment returned
      to normal spontaneously at one year.

PMID- 17457285
TI  - [Disseminated intravascular coagulation syndrome and thromboembolic complications
      of non-small-cell lung cancer. A case report].
AB  - Hemostatic disorders can be found in approximately 90% of cancer patients, but
      clinical expression in only 15%. Hemorrhagic complications are more frequent in
      acute leukaemia; solid tumors are often associated with deep venous thromboses
      (DVP). Disseminated intravascular coagulation syndrome (DICS) can be latent or
      acute, and has various clinical presentations, occurring in the course of many
      serious conditions including cancer. Patients have higher morbidity and
      mortality. Irrespective of the etiology, DICS can be revealed by a wide variety
      of clinical manifestations, from mild biological hemostasis disorders, to
      intravascular or extravascular microthromboses or lethal hemorrhagic events. We
      report the case of a 45-year-old female with non-small-cell lung cancer with
      metastases at diagnosis. The patient developed and finally died of numberous
      thromboembolic events subsequent to DICS. This case illustrates some rather rare
      complications of DICS and offers the opportunity to discuss the main therapeutic
      goal in this situation, i.e. to modulate the disproportionate production of
      thrombin, inducing thromboses and/or hemorrhages by consumption of the cellular
      and plasmatic coagulation factors. This means a symptomatic and mostly etiologic
      treatment, especially chemotherapy which can in itself provoke thromboembolic
      events.

PMID- 17457286
TI  - [Three-year survival after treatment of a primary pulmonary angiosarcoma].
AB  - We report an observation of angiosarcoma of the pulmonary artery in a 65-year-old
      man hospitalized for acute dyspnea revealing a left mass hilaire which arose from
      the pulmonary artery before the development of obstructive endobronchial
      extension. The therapeutic sequence associated removal of the lobar bronchus
      obstruction by interventional endoscopy, chemotherapy using ifosfamide
      doxorubicin, complete left pneumonectomy and auxiliary chemotherapy with 2
      additional cycles. The patient was free of tumor relapse at nearly 3 years follow
      up.

PMID- 17457287
TI  - [Intrapulmonary thymic choristoma].

PMID- 17457288
TI  - [Multifocal (spinal cord, thorax, abdomen) severe complicated hydatid disease].

PMID- 17457289
TI  - [A rare tumor of the thoracic wall: solitary malignant fibrous tumor].

PMID- 17457290
TI  - [Link between depression and academic self-esteem in gifted children].
AB  - INTRODUCTION: Studies of the psychology of gifted children frequently refer to
      their relatively immature affective development in terms of their intellectual
      capacities and the relational difficulties they experience with regard to their
      peers, teachers, close acquaintances and sometimes their parents. From a
      psychopathological viewpoint, various types of problem have been observed such as
      depressive symptoms, motor instability coupled with hyperactivity, attentional
      deficits, impulsivity and a fall in self-esteem. OBJECTIVE: In this study, we
      wished to verify the links between self-esteem and psychopathological symptoms in
      these children. METHOD: The total population studied consisted of 58 pupils taken
      from two teaching establishments in Dijon who were subdivided into two groups
      (gifted children and adolescents versus control children and adolescents). Of
      these 58 subjects who took part in the tests, 8 were eliminated either due to
      their results on the "lie" scale of the self-esteem scale (score greater than or
      equal to 5) or to their age. In effect, a high score on this scale implies that
      the subjects want to show themselves in a better light than is actually correct.
      It is then assumed that the subjects had sought the examiner's approval by
      presenting the best possible image of themselves; 23 gifted children, referred to
      as GC (10 girls, 13 boys) aged between 9 and 13 years (mean age=11 years 3 months
      or 135 months, standard deviation=14) took part in the study. The selection
      criteria required the subjects to possess an Intelligence Quotient (IQ)
      calculated using one of the Weschler tests (WPPSI or WISC III depending on age)
      greater than or equal to 130 (mean IQ=145.23, standard deviation=7.93); 20 were
      attending private schools and 3 were in the state education system. They were all
      attending special "GC" classes to which they had been admitted solely on the
      basis of an IQ test conducted by a psychologist. Their teachers had volunteered
      to take these classes and had received appropriate training. The pupils had no
      record of any neurological or physical antecedents, were all French-speaking,
      were not taking any toxic substances and had never consulted a psychologist or
      psychiatrist. They were all in advance by one to two years in terms of academic
      level. They were matched with the control subjects by real age and not mental age
      and as a function of their parents' socio-economic level. The mean age of this
      latter group was 11 years, 4 months (standard deviation=14 months; minimum=8
      years 11 months, maximum=13 years 1 month) and the group consisted of 14 girls
      and 9 boys. It was similar to the target group in terms of age, gender, key
      childhood experiences, divorces, separations and the death or illness of close
      relations. They had never consulted a child psychologist or been hospitalized for
      related problems, were not following any psychotherapy, were neither behind nor
      advanced in terms of academic age and came from normal classes. Their mean
      Intelligence Quotient (IQ) was 106.04 (standard deviation=5.39). Children
      attending special classes (European, Franco-German, music, sport, etc.) were
      excluded in order to obtain as "standardized" a group as possible. The following
      tools were used: 1) The Child Behaviour Check List (CBCL), a self-questionnaire
      developed in 1978 by Achenbach in the USA, which is one of the most frequently
      used child psychopathology measuring tools both in research and in clinical
      practice. It is intended to provide a standardized description of emotional
      and/or behavioral problems as observed by parents in children aged between 4 and
      16 years. A French version, "la liste des comportements pour les enfants", has
      been developed and used for a subsample of the boys aged between 6 and 11 years
      (Fombonne and Vermeersch, 1997). 2) Carre's "self-esteem inventory" (SEI) was
      created by Carre (1984) in order to test the level of self-esteem. This tool is
      designed to measure the subject's evaluation of himself or herself in the social,
      family, academic and general fields. A "lie" scale makes it possible to reject
      invalidated tests. 3) The EDICODE is an instrument designed to gather and
      quantify the speech produced by the subject during a semi-structured interview.
      It is rated by the interviewer and is therefore dependent on his or her
      subjective evaluation. It was constructed within a clinical research perspective
      (Pierrhumbert et al., 1999) and is based on the theory of attachment (Main and
      Goldwyn, 1985-1994). EDICODE consists of 21 items presented in the form of
      differential semantic scales. These items are then grouped into 5 factors or
      scales (containing non-redundant items) that cover the following dimensions:
      fluidity (associative richness, ease of access to memories, participation in the
      interview), coherence (the speech is "focused" and structured), appropriateness
      (appropriate relational distance, confidence in relations, capacity for emotional
      control), reflection (consideration of one's own mental state and that of others
      as well as of the influence of such states), authenticity (spontaneous, lively
      speech). RESULTS: The comparison of 23 gifted children (GC) and 23 controls
      matched on age, sex and school grade revealed that the scores for academic self
      esteem, total self-esteem and lie-scale were significantly lower than those
      observed in the control group (p<0.006, p=0.03, p<0.0001 respectively) and that
      the depression scores were significantly higher in the gifted children (p=0.021).
      Significant correlations are only observed in the group of gifted children. The
      correlation analyses reveal that the lower the general self-esteem, academic self
      esteem and total self-esteem values had fallen, the higher the depression (r=-
      0.59, r=- 0.67 and r=- 0.76 respectively), hyperactivity (r=- 0.47, r=- 0.82 et
      r=- 0.59) and total psychopathology (r=- 0.56, r=- 0.67 et r=- 0.75) scores were.
      Similarly, the lower the general and total self-esteem scores, the higher the
      aggression scores (r=- 0.56 and r=- 0.68 respectively). Academic self-esteem was
      the only value to be negatively correlated with communication disorders (r=-
      0.79) and somatization symptoms (r=- 0.49). Finally, social self-esteem, family
      self-esteem and the lie scale were not correlated with any CBCL variable. The
      regression analyses indicate that academic self-esteem is the variable that
      explains the depression scores. DISCUSSION: The gifted children in our study
      therefore manifested a lack of self-esteem, and in particular a lack of academic
      self-esteem, coupled with depressive symptoms. For Coopersmith (1984), self
      esteem is a function of experienced events in the various sectors in question,
      while Gibello (1992) sees a link between inhibition or academic disinvestment and
      everything that may generate anxiety and/or depression in the subject. We can
      hypothesize that the difficulties experienced by these children derive, at least
      in part, from their specific characteristics, namely their internal and social
      dysschynchronism (Terrassier, 1981). Among its other effects, this dyssynchronism
      leads to a school life that is often difficult or even chaotic, resulting in a
      general level of self-esteem, and more particularly an academic self-esteem, that
      is lower than the mean. These considerations might then, in their turn, generate
      psychopathological symptoms such as depression or hyperactivity (Revol et al.,
      2002) which have repercussions that affect the effectiveness of the children's
      school work. This study suggests the need to verify whether similar results are
      observed in gifted children who do not attend special classes and children who
      have not yet been identified as gifted. Furthermore, our results indicate that
      these children are liable to a specific vulnerability in the emotional and
      behavioral domains that needs to be emphasized. They stress the need for early
      preventive measures to combat the emotional and behavioral difficulties
      experienced by gifted children and emphasize the importance of continuing to
      conduct this type of study in order to explain and specify the origin of these
      difficulties.

PMID- 17457291
TI  - [Schizophrenia and culture: reality and perspectives based on the Tunisian
      experience].
AB  - Despite notable advances in the field, schizophrenia is still considered a major
      public health problem on international level. The combination of frequency,
      chronicity and severity make it, for some authors, the "cancer of mental
      disorders". However, according to the many cross-cultural studies, in particular,
      the two mammoth research projects of the WHO (IPSS and DOSMED, it is now
      irrefutable that the course and outcome of schizophrenia are better in patients
      from developing countries. The reasons for better outcome and more favorable
      course of schizophrenia in developing countries are still far from clear and
      remain speculative. AIM OF THE STUDY: We have carried out a study among a
      population of schizophrenic patients admitted to our hospital during the past
      year, to question the issues of outcome, course and prognosis in Tunisia, which
      is an emerging country, ranking half-way between the most and the least developed
      countries. RESULTS: It appears that the outcome of schizophrenia is similar to
      that of developed countries. A community survey reported an annual prevalence of
      5.7 and an incidence of 3. 266 patients with schizophrenia were admitted between
      August 2003 and 2004, representing 40% of the whole hospitalized population; 80%
      were former patients who had been hospitalized an average of 8 times. One patient
      out of five will be readmitted at least once within the same year. Only 16.5%
      were married, and 10% had a regular job, in spite of a high level of education. A
      chronic course without remission is not unusual and long stay patients now
      account for a fourth of the hospital population. COMMENTS: It seems clearly and
      paradoxically that the course and outcome of schizophrenia is deteriorating and
      getting closer to what is observed in the industrialized societies. The same
      trend was observed in the western countries during the last centuries, leading
      some authors to claim that schizophrenia is a modern disease, which appeared in
      the XIX(e) century and spread in the XX(e). Besides, other than the controversy
      regarding the recent evolution of its incidence, it seems that we are not
      witnessing the anticipated decrease in incidence that comes with the therapeutic
      progress and the decline in fertility among individuals with schizophrenia.
      DISCUSSION: We shall discuss three hypotheses to try to explain the aggravation
      of schizophrenia along with the economic development: the heterogeneity of the
      disease with two clinical presentations: a benign form (good prognosis), more
      frequent in developing countries, and a severe form, observed mainly in developed
      societies. The progress in medicine and gynecology-obstetrics, which contributes
      to the survival of patients with serious schizophrenia and the vulnerable newborn
      exposed to multiple assaults and risk factors related to birth. The progress in
      psychiatry that is selecting the more serious subtypes of schizophrenia, which
      are overrepresented today. Research issues pertaining to course and outcome of
      schizophrenia are still unresolved. It is likely that prognosis of schizophrenia
      varies according to the economic development rather than to the culture. This
      observation could open new research and prevention perspectives.

PMID- 17457293
TI  - [Validity of vascular depression as a specific diagnostic: a review].
AB  - INTRODUCTION: A number of authors have suggested that cerebrovascular disease may
      predispose, precipitate, or perpetuate some geriatric depressive syndromes. These
      "vascular depressions" may result from damage of striato-pallido-thalamo-cortical
      pathways which frequently occurs in cerebrovascular disease. METHOD: We have
      searched the English and French literature published between 1996 (when the
      "vascular depression" hypothesis was first stated) and December 2004 through the
      Medline computer database and examined the validity of the concept of "vascular
      depression" thanks to four levels of validity: face validity, descriptive
      validity, construct validity and predictive validity. The face validity is the
      extent to which experts agree about the existence of a nosological entity.
      RESULTS: The reviews published in this field broadly support the concept of
      "vascular depression" as a specific disorder. However many authors highlighted
      the fact that depression has been shown to precede vascular diseases and that
      depression and vascular diseases may both share some pathogenic or genetic
      determinants. These interactive and co-morbid relationships between depression
      and cerebrovascular diseases are difficult to disentangle. The descriptive
      validity refers to the degree of the clinical specificity of a disorder. It
      appears only moderate regarding the clinical studies carried out on this issue.
      However, a late-onset, the absence of a family history of mental illness, the
      lack of insight, lassitude, psychomotor retardation, a greater disability and
      particular neuropsychological dysfunctions may be associated with vascular
      depression. The construct validity, which refers to the degree to which the
      physiopathological processes involved in an illness are understood, appears
      difficult to establish because of the complex interactive relationships between
      cerebrovascular disease and depression. However, cerebrovascular diseases may
      contribute to the occurrence of depressive symptoms independently of its
      psychosocial burden. The predictive validity refers to the degree to which a
      syndrome is characterized by a specific response to treatment or a specific
      natural history. As regards response to treatment, vascular depression appears
      rather specific in the sense of a worse response to antidepressants and
      electroconvulsive therapy. The studies on the natural history of vascular
      depression lead to inconsistent results. According to some authors, this relative
      resistance to treatment may be explained by structural rather than functional,
      and thus potentially irreversible disruption in neural networks. CONCLUSION: In
      conclusion, the systematic review of the validity of vascular depression broadly
      supports this concept. However, further studies are needed to decipher the
      relationships between depression and cerebrovascular disease. Finally, we suggest
      that it could be more relevant for future researches in this field if the
      diagnostic criteria for vascular depression were narrowed and required the
      presence of both neuro-imaging changes and cerebrovascular disease.

PMID- 17457292
TI  - [Anxiety and depressive disorders in 4,425 long term benzodiazepine users in
      general practice].
AB  - Consumption rates of anxiolytic drugs, and especially of benzodiazepines, remain
      very high in France compared to other Western countries, whereas clinical
      guidelines limit their indications to short term treatments and only for some
      precise anxiety disorders. Recent epidemiologic surveys in the community
      indicated that more than 15% of people used once or more an anxiolytic drug in
      the past year. The issue of chronic treatments is particularly crucial because of
      their poor benefit/risk ratio in most anxiety disorders (limited efficacy,
      cognitive side effects, withdrawal and dependence problems). To address this
      important public health issue, and knowing that, in France, benzodiazepines are
      prescribed mainly by general physicians, our aims were to explore psychiatric
      diagnoses in GP's patients with chronic use of anxiolytic benzodiazepines. We
      included 4 425 patients consuming such drugs regularly for six months or more,
      and assessed their anxiety and depression symptoms through various clinical
      scales (Hospital Anxiety and Depressive scale - HAD, Clinical Global Impression
      scale - CGI, Sheehan Disability Scale - SDS, Cognitive Dependence to
      Benzodiazepines scale - CDB) and with the Mini International Neuropsychiatric
      Interview for DSM IV criteria. Only 2.2% of the subjects had neither anxious nor
      depressive symptoms as indicated by low scores on both subscores (less than 8) of
      the HAD scale, used as a screener. Nearly three quarters of the 4,257 subjects
      (73.2%), had CGI scores of at least 5 (markedly ill to extremely ill). Social and
      familial disability was also high in more than 40% of the sample (marked to
      extreme disruption according to SDS scores). About half of the sample had CDB
      scores suggesting a benzodiazepine dependence. According to the MINI, 85.1% of
      the patients had at least one current DSM IV diagnosis of affective disorder. The
      most frequent diagnoses were major depressive episode (60%), generalized anxiety
      disorder (61.2%), and panic disorder (22.5%). An anxiety and depressive
      comorbidity wad found in 41.9% of the subjects. Some methodological limitations
      must be taken into account in the discussion of our results, and especially the
      fact that the included patients were not supposed to be totally representative of
      all patients consuming anxiolytic benzodiazepines in general practice. However,
      the size of our sample is sufficiently large to limit possible biases in patient
      selection. The main result of this study is that a great majority of the patients
      had significant symptomatology, in particular major depressive episodes and
      generalized anxiety disorder, often with marked severity and disability. These
      data are in line with the knowledge of a lack of efficacy of benzodiazepines in
      depressive and most anxiety disorders, despite long term treatment. They also
      confirm the current guidelines which recommend prescribing serotoninergic
      antidepressants, and not benzodiazepines, when long term treatments are needed
      for severe and chronic affective disorders. This epidemiologic study leads to the
      conclusion that a specific and attentive diagnostic assessment should be done in
      all patients receiving benzodiazepines for more than three months, in order to
      purpose in many cases other long term therapeutic strategies.

PMID- 17457294
TI  - [Validation of EHD self questionnaire in multiple sclerosis].
AB  - Depressive Mood Scale (EHD) aims at assessing the various depressive mood
      dimensions as "blunted affect" and "lack of emotional control". It is an 18 items
      hetero-evaluation scale. The aim of this study was the validation of an EHD self
      questionnaire version. Self questionnaire items were generated from genuine scale
      items. As in the former version, response format was a Lickert 5 point scale.
      This validation study was carried out on 77 Multiple Sclerosis (MS) patients.
      Mood disorders are frequent during the course of MS and might be triggered or
      worsened by immuno-modulation therapies. Principal Component Analysis (ACP) with
      Varimax rotation revealed a two factors structure. The first one, corresponding
      to a "blunted affect" dimension, explained 33.5% of the scale variance and was
      composed of 7 items. The second one, corresponding to a "lack of emotional
      control" dimension, explained 20% of total scale variance and was composed of 4
      items. The questionnaire internal coherence coefficient (Cronbach alpha) was
      excellent (=0.87) and the two sub-scales ones were satisfactory [0.89 for
      "blunted affect" dimension and 0.71 for "lack of emotional control" dimension.
      The questionnaire's external validity was confirmed by a positive correlation
      between "lack of control" sub-score and state sub-score of the Stait-Trait Anger
      eXpression Inventory (STAXI)] (r=0.55, p<0.01). Moreover we found a positive
      correlation between the total EHD autoquestionnaire score and both sub-scores on
      the one hand, and the Beck Depression Inventory score on the second hand
      (EHD/BDI: r=0.76, p<0.01; "lack of emotional control"/BDI: r=0.68, p<0.01;
      "blunted affect"/BDI: r=0.63, p<0.01). Test-retest reliability was good with a
      positive correlation between all the initial scores and their retests, a week
      later. Secondarily, a structural equation modeling analysis confirmed the two
      factors structure model suggested by ACP. Various indicators showed a good fit
      between theoretical variance-covariance matrix and the observed one
      (chi(2)=41.55, p=0.49, ddl=42, Goodness Fit Index GFI=0.91, Root Mean Square
      Residual RMSEA=0.00). Thus, we proposed a well validated self questionnaire that
      allows the assessment of "blunted affect" and "lack of emotional control". It
      should be challenging to correlate those dimensions with neuro-psycho-logical
      testing and neuro-imagery, in patients affected by CNS diseases. Moreover, the
      assessment of those dimensions during interferon treatment in MS could allow a
      more precise evaluation of the emotional changes potentially induced by immuno
      modulatory treatments.

PMID- 17457295
TI  - [2-COM: presentation of an instrument facilitating communication between
      physicians and carers in daily practice].
AB  - Communication between the patient and the professional carer lies at the heart of
      all decisions regarding diagnosis and treatment. However, patients and doctors
      often have divergent views on care needs; 2-COM (for 2-communication) is a simple
      patient-completed self-report instrument designed in order to facilitate patient
      professional carer communication. Aims - To present 2-COM and to examine whether
      providing patients with an opportunity to identify and discuss their needs would
      improve communication and induce changes in care. Methods - The 2-COM is a simple
      list of 20 common problems, or areas of perceived need, that might be experienced
      by patients with severe mental illness. The list includes problems with housing,
      relationships, money, lack of activities, psychological distress, sexuality,
      symptoms and treatment side effects; 2-COM has shown adequate test-retest
      reliability and is well accepted by patients as a valued aid to communication
      with their doctor; 134 patients in a clinical diagnosis of schizophrenia or
      schizoaffective disorder were recruited at seven European centres: Maastricht,
      Oviedo, Gijon, Hamburg, Copenhagen, Milan and Nice. The assessment took place
      over 3 out patient clinic visits; at visit 1, the clinician recorded a list of
      all current interventions, including medication and non-medical treatments,
      together with demographic information and an assessment of current level of
      functioning, using the Global Assessment of Functioning scale. Prior to the
      second visit, patients were randomised to receive either 2-COM or "standard care"
      - a routine appointment without 2-COM. Immediately after the interview, all
      patients, whether they had completed 2-COM or not, completed a confidential
      questionnaire in which they could indicate the perceived quality of
      communication. Similarly, clinicians completed a repeat of the list of all
      current interventions, together with an assessment of any changes to the
      treatment plan implemented after the interview with the patient. Four to six
      weeks after clinic visit 2, patients attended the clinic for a third, "routine"
      clinical interview. Both patients and clinicians then completed the same set of
      post-interview assessments as at visit 2. The 2-COM induced a stable improvement
      of patient-reported quality of patient-doctor communication (B=0.33, P=0.031),
      and induced changes in management immediately after the intervention. Treatment
      change was more likely in patients with more reported needs at the 2-COM and
      needs most likely to induce treatment changes. In conclusion, the study showed
      that 2-COM is a useful instrument to expose and subsequently bridge, patient
      professional carer discordance on patient needs.

PMID- 17457296
TI  - [Psychotherapeutic practices in France: results of a professional-based health
      insurance participant survey].
AB  - INTRODUCTION: Today in France, little empirical data on the use of psychotherapy
      is available. This paper presents an empirical study of psychotherapeutic
      practices, from the patient's point of view. We will present results regarding
      frequency of psychotherapies, patients' characteristics, associations between
      different kinds of therapy, where they take place, and the reasons given for
      beginning psychotherapy. METHODOLOGY: Data is based on a general and mental
      health survey conducted by MGEN(1) foundation among 6,500 persons, as well as on
      general population data collected by the BVA survey institute. RESULTS: Depending
      on the population studied, between 5 to 11.5% of people have had psychotherapy
      sessions at least once in their lifetime. Women born at the beginning of the
      sixties and men born at the beginning of the fifties are those who consulted the
      most. The vast majority of these psychotherapies are individual, in private
      practice. They often last more than one year, with a frequency of once per week
      or more. Thirty percent declare that they have undergone several psychotherapies.
      The reasons for consultation reported by users are mainly depression or anxiety.
      There are significant differences between genders for the reasons for
      consultation, women being concerned by depression, problems with sleep and food,
      and men being concerned by obsessive thoughts and addiction (alcohol, tobacco).
      People undergoing psychotherapy give an average of 2.5 reasons for this
      psychotherapy, and only 28% gave only one reason. A relationship exists between
      the number of consecutive treatments and the number of reasons given for
      undergoing psychotherapy. More than 25% of the psychotherapies last less than 6
      months. "Intensive psychotherapy" (at least 6 months and a frequency of 2 to 3
      times per month) concern 5.9% of the whole population studied, and represent
      51.4% of all psychotherapies. People are quite satisfied by their psychotherapy;
      90% are satisfied with the results and 60% believe that their condition has been
      much improved in a durable manner. 16.6% were unsatisfied with the results. There
      is (in women only) an association between satisfaction and intensity of
      treatment; satisfaction is lower in those women undergoing intensive
      psychotherapy; 77. 7% of users have also used some sort of drugs for the problem
      (80.6% of women and 69.9% of men) with psychotropic drugs most frequently used:
      70.8% of the psychotherapy users had taken such drugs for their problem (women
      72.9%, men 65.4%). CONCLUSION: In France, psychotherapies are playing an
      important role and it is necessary to study these techniques better in order to
      give them the place they deserve in the French mental health policy.

PMID- 17457297
TI  - [Perception of everyday life by schizophrenic patients and nurses: content
      analysis of patients' speech on different domains of quality of life].
AB  - INTRODUCTION: The validation of a questionnaire of subjective quality of life was
      used as pretext to question the way in which various fields of the everyday life
      were understood by schizophrenic subjects and nursing team members. Content
      analysis allowed the development of logico-semantic categories shared by the two
      populations and likely to give body to the subjacent social representations.
      METHOD: Patients were asked to comment on the different items of the SQUALA.
      Patients' and nurses' answers for each item were grouped and the analysis was
      conducted on this corpus. For each item, the different points of view were
      summarised into categories of signification. RESULTS: The results are presented
      item by item. The most important points are the followings: perceived health,
      physical autonomy, mental well-being and safety are linked to social and
      relational aspect of patients' life. Abstract concepts could be questioned among
      schizophrenic patients. It was possible to establish coherent categories. The
      analysis of certain unclassifiable statements makes it possible to specify
      phenomenological aspects of the schizophrenic experience. DISCUSSION:
      Methodological limitations of this study are essentially due to content analysis
      methodology (standardisation of answers, choice of categories) and to the
      characteristics of the populations selected.

PMID- 17457298
TI  - [Pharmacological treatment of generalized anxiety disorders: rationale and
      limitations].
AB  - The rational use of pharmacological treatment in generalized anxiety disorders is
      still a matter of debate due to the uncertainties concerning the nature,
      diagnostic criteria and target-symptoms of this frequent and potentially
      invalidating disorder. If benzodiazepines may still be prescribed for a limited
      amount of time (i.e. 6 to 12 weeks) due to the fluctuating nature of generalized
      anxiety, the chronic evolution of this disorder in most patients often justifies
      the long-term prescription of serotoninergic (5-HT) or dual-action (5HT-NA)
      antidepressants and sometimes of 5HT-la partial agonists like buspirone.
      Imipramine, a tricyclic antidepressant was the first to demonstrate its efficacy
      in carefully selected patients; however, due to the side-effects of this molecule
      recent guidelines based on controlled clinical trials, suggest to use either
      serotonergic antidepressants (SSRIs) or venlafaxine as a first-line treatment of
      generalized anxiety disorders. Because of its pharmacological profile buspirone
      remains however a useful option in patients with cognitive or addictive problems,
      especially alcoholics. If most SSRIs have demonstrated efficacy over placebo,
      head to head comparisons remain limited except for escitalopram which appear
      better tolerated than paroxetine in this indication. More recently, an
      anticonvulsant, pregabaline also demonstrated its efficacy in several clinical
      trials but the symptomatic profile of generalized anxiety patients likely to
      respond to this GABA analog compared to other psychotropic treatments remain to
      be established. The traditional use of other psychotropic agents such as
      hydroxyzine, an H1 histaminergic receptor antagonist, is only supported by
      limited scientific data; this is also the case of sedative typical antipsychotics
      which benefit/risk ratio should be carefully evaluated before being prescribed to
      generalized anxiety patients resistant to other psychotropic agents. However, the
      possible use of atypical antipsychotics with a better tolerance profile than the
      typical ones in this indication is presently under investigation in several
      countries. At last it is important to realize that most clinical trials in this
      field only include patients with non-comorbid generalized anxiety and that their
      conclusion may not always be generalizable to most psychiatric patients who are
      usually characterized by a high rate of comorbidity. In this population the
      indication of specific pharmacological treatments should rely on a careful
      evaluation of the patients drug treatment history, of the duration, evolution and
      functional consequences of their symptoms and of the nature of their possible
      comorbidity. The treatment of resistant generalized anxiety disorders remains a
      question for future research but the use of imipramine or sedative antipsychotics
      could be an option when other treatments have failed to induce any improvement.

PMID- 17457299
TI  - [Postoperative dementia: toxicity of nitrous oxide].
AB  - INTRODUCTION: Post-operative neuropsychiatric manifestations represent a frequent
      situation and may be due to several aetiologies. The responsibility of vitamin
      B12 deficiency must be evoked, especially in case of anaesthesia with a currently
      used substance: nitrous oxide. CASE REPORT: A 65 year-old man with no medical
      history, presented problems walking and memory loss 16 days after surgery for
      femoral prosthesis. Neurological examination revealed paraplegia with syndrome of
      combined degeneration of the spinal cord. The exploration of cognitive functions
      showed disorientation in time with memory disorders and disturbance of executive
      functioning. There was no apraxia, aphasia or agnosia. There were neither
      psychotic symptoms nor mood changes. MMS was at 18/30. Red blood count revealed
      an anaemia with macrocytosis (MGV=120 3). Vitamin B12 rate was very low (less
      than 30 g/l). Folate blood level was normal. Brain MRI showed moderate cerebral
      atrophy. Other investigations led to the diagnosis of Biermer's disease (fundic
      atrophy at biopsy with presence in the serum of antibodies to intrinsic factor).
      The diagnosis of neurological attack related to a vitamin B12 deficiency
      secondary to Biermer's disease was established, but the appearance of disorders
      in the post-operative period suggested the existence of an added factor. The
      recovery of informations revealed that anaesthesia was maintained by nitrous
      oxide during two hours and the patient exhibited pre-operative anaemia with
      macrocytosis. The hypothesis of decompensation of latent vitamin B12 deficiency
      by nitrous oxide was evoked. Replacement therapy by vitamin B12 induced real
      improvement of the cognitive impairment. MMS increased to 25/30. DISCUSSION:
      Cognitive impairment due to vitamin B12 deficiency is rarely dominated by
      isolated memory disorders. An authentic dementia is exceptional. Our patient had
      a dementia diagnosed on the basis of DSM IV criteria including memory disorders,
      disturbance of executive functioning and significant impairment in social and
      occupational functioning, associated with a combined degeneration of the spinal
      cord, common in vitamin B12 deficiency. Furthermore, he had an unknown Biermer's
      disease responsible for pre-operative deficiency which was clinically latent
      (there was only macrocytosis anaemia). The appearance of problems in the post
      operative period was due to an acute decompensation of the latent deficiency
      induced undoubtedly by nitrous oxide used in anaesthesia. According to
      Christensen, nitrous oxide causes irreversible oxidation of vitamin B12 cobalt's
      atom responsible for its inactivation and the appearance of clinical
      manifestations. Evolution under vitamin B12 replacement therapy depends on the
      rapidity of its founding. In our case, it led to an improvement, notably in
      cognitive functions. CONCLUSION: Through this observation, the authors underline
      the necessity to search for vitamin B12 deficiency in the case of cognitive
      features following general anaesthesia.

PMID- 17457300
TI  - The Delta paradox: DLL4 blockade leads to more tumour vessels but less tumour
      growth.
AB  - Anti-angiogenesis therapies have emerged as important treatment options for
      several types of tumours. To date, these therapies have focused on blocking the
      vascular endothelial growth factor (VEGF) pathway. A recent series of papers have
      shown that one ligand for the Notch receptors, Delta-like ligand 4 (DLL4), is
      normally induced by VEGF and is a negative-feedback regulator that restrains
      vascular sprouting and branching. Consistent with this role, the deletion or
      inhibition of DLL4 results in excessive, non-productive angiogenesis. This
      unrestrained angiogenesis unexpectedly and paradoxically decreases tumour growth,
      even in tumours resistant to anti-VEGF therapies. Can too much angiogenesis be
      bad for tumours but good for patients?

PMID- 17457301
TI  - Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition.
AB  - Cancer therapy has progressed remarkably in recent years. In no area has this
      been more apparent than in the development of "targeted therapies", particularly
      those using drugs that inhibit the activity of certain tyrosine kinases,
      activating mutations or amplifications of which are causal, or strongly
      contributory, to tumorigenesis. However, some of these therapies have been
      associated with toxicity to the heart. Here we summarize what is known about the
      cardiotoxicity of cancer drugs that target tyrosine kinases. We focus on basic
      mechanisms through which interruption of specific signalling pathways leads to
      cardiomyocyte dysfunction and/or death, and contrast this with therapeutic
      responses in cancer cells.

PMID- 17457302
TI  - Second generation inhibitors of BCR-ABL for the treatment of imatinib-resistant
      chronic myeloid leukaemia.
AB  - Imatinib, a small-molecule ABL kinase inhibitor, is a highly effective therapy
      for early-phase chronic myeloid leukaemia (CML), which has constitutively active
      ABL kinase activity owing to the expression of the BCR-ABL fusion protein.
      However, there is a high relapse rate among advanced- and blast-crisis-phase
      patients owing to the development of mutations in the ABL kinase domain that
      cause drug resistance. Several second-generation ABL kinase inhibitors have been
      or are being developed for the treatment of imatinib-resistant CML. Here, we
      describe the mechanism of action of imatinib in CML, the structural basis of
      imatinib resistance, and the potential of second-generation BCR-ABL inhibitors to
      circumvent resistance.

PMID- 17457303
TI  - Tumour microenvironment: laminin 332 in squamous-cell carcinoma.
AB  - Basement membranes can be a barrier to tumour growth, but basement membrane
      molecules, including laminins, are also important autocrine factors produced by
      cancers to promote tumorigenesis. Many studies have shown the importance of
      laminin 332 (previously known as laminin 5) in this process, especially in
      squamous cell carcinoma. Through interactions with several cell-surface receptors
      (including alpha6beta4 and alpha3beta1 integrins, epidermal growth factor
      receptor and syndecan 1) and other basement membrane components (including type
      VII collagen), laminin 332 drives tumorigenesis through phosphatidylinositol-3
      kinase (PI3K) and RAC1 activation, promoting tumour invasion and cell survival.
      The extracellular interactions of laminin 332 appear amenable to antibody
      mediated therapies.

PMID- 17457304
TI  - Suppressive effects of antiandrogens, finasteride and flutamide on development of
      prostatic lesions in a transgenic rat model.
AB  - Transgenic (TG) rats bearing a probasin promoter/simian virus 40 T antigen (SV40
      Tag) construct were treated with antiandrogens to examine their ability to
      suppress prostate carcinogenesis. Finasteride and flutamide were administered to
      10-week-old TG rats five times a week for 2, 5 and 7 weeks. Antiandrogen-treated
      prostates exhibited atrophic glandular structures with almost no expression of
      SV40 Tag and only weak signals for androgen receptors. Furthermore, quantitative
      data for ventral prostate adenocarcinomas showed significant decrease with
      antiandrogen treatment. Both finasteride and flutamide had the ability to
      suppress SV40 Tag-driven carcinogenesis through their different antiandrogenic
      mechanisms, suggesting that this TG model is suitable for exploring the potential
      of agents to inhibit prostate cancer development.

PMID- 17457305
TI  - Increased expression of anterior gradient-2 is significantly associated with poor
      survival of prostate cancer patients.
AB  - Anterior gradient-2 (AGR2) expression was examined in a series of prostate cell
      lines and in an archival set of prostate tissues. The relative levels of AGR2
      expression in the malignant cell lines PC-3 and PC-3M were, respectively, 5.3+/
      0.1 and 3.8+/-0.2 times that detected in the benign cell line PNT-2.
      Immunohistochemical staining in 106 cases showed that amongst seven normal cases,
      one (14.3%) was unstained, five (71.4%) stained weakly positive and one (14.3%)
      stained moderately positive. Amongst 34 benign prostate hyperplastic (BPH) cases,
      12 (35.3%) were unstained, 18 (52.9%) stained weakly positive and four (11.8%)
      stained moderately positive. Amongst 65 carcinomas, three (4.6%) were unstained,
      14 (21.5%) stained weakly positive, 19 (29.2%) stained moderately positive and 29
      (44.9%) stained strongly positive. AGR2 expression in carcinomas was
      significantly higher than that in BPH (chi(2)-test, P<0.001). Kaplan-Meier
      survival analysis showed that increased AGR2 expression was significantly (log
      rank test, P=0.007) associated with reduced patient-survival time. Increased
      joint Gleason score (GS) was significantly (log rank test, P=0.001) associated
      with poor patient survival. However, neither prostate specific antigen (PSA)
      level, nor androgen receptor (AR) index, was significantly associated with
      patient-survival time. Increased AGR2 expression was significantly correlated
      with high GS (two-sided Fisher's exact test, P<0.001) and PSA levels (Mann
      Whitney U-test, P=0.047), but not significantly related to the level of AR (Mann
      Whitney U-test, P=0.286). These results suggest that increased AGR2 expression is
      a valuable prognostic factor to predict the clinical outcome of the prostate
      cancer patients.

PMID- 17457306
TI  - Does addition of sitagliptin to metformin monotherapy improve glycemic control in
      patients with type 2 diabetes mellitus?

PMID- 17457307
TI  - Growth hormone and thyroid function-interaction and inhibition.

PMID- 17457308
TI  - Is barium column surface area a better predictor of primary achalasia disease
      severity than barium column height?

PMID- 17457309
TI  - What is the best way of screening hemodialysis patients for latent tuberculosis?

PMID- 17457310
TI  - Lumbar disc herniation--to operate or not to operate?

PMID- 17457311
TI  - Heart failure in childhood cancer survivors.

PMID- 17457312
TI  - The immune-mediated alteration of serotonin and glutamate: towards an integrated
      view of depression.
AB  - Beside the well-known deficiency in serotonergic neurotransmission as
      pathophysiological correlate of major depression (MD), recent evidence points to
      a pivotal role of increased glutamate receptor activation as well. However, cause
      and interaction of these neurotransmitter alterations are not understood. In this
      review, we present a hypothesis integrating current concepts of neurotransmission
      and hypothalamus-pituitary-adrenal (HPA) axis dysregulation with findings on
      immunological alterations and alterations in brain morphology in MD. An immune
      activation including increased production of proinflammatory cytokines has
      repeatedly been described in MD. Proinflammatory cytokines such as interleukin-2,
      interferon-gamma, or tumor necrosis factor-alpha activate the tryptophan- and
      serotonin-degrading enzyme indoleamine 2,3-dioxygenase (IDO). Depressive states
      during inflammatory somatic disorders are also associated with increased
      proinflammatory cytokines and increased consumption of tryptophan via activation
      of IDO. An enhanced consumption of serotonin and its precursor tryptophan through
      IDO activation could well explain the reduced availability of serotonergic
      neurotransmission in MD. An increased activation of IDO and its subsequent enzyme
      kynurenine monooxygenase by proinflammatory cytokines, moreover, leads to an
      enhanced production of quinolinic acid, a strong agonist of the glutamatergic N
      methyl-D-aspartate receptor. In inflammatory states of the central nervous
      system, IDO is mainly activated in microglial cells, which preferentially
      metabolize tryptophan to the NMDA receptor agonist quinolinic acid, whereas
      astrocytes - counteracting this metabolism due to the lack of an enzyme of this
      metabolism - have been observed to be reduced in MD. Therefore the type 1/type 2
      immune response imbalance, associated with an astrocyte/microglia imbalance,
      leads to serotonergic deficiency and glutamatergic overproduction. Astrocytes are
      further strongly involved in re-uptake and metabolic conversion of glutamate. The
      reduced number of astrocytes could contribute to both, a diminished
      counterregulation of IDO activity in microglia and an altered glutamatergic
      neurotransmission. Further search for antidepressant agents should take into
      account anti-inflammatory drugs, for example, cyclooxygenase-2 inhibitors, might
      exert antidepressant effects by acting on serotonergic deficiency, glutamatergic
      hyperfunction and antagonizing neurotoxic effects of quinolinic acid.

PMID- 17457313
TI  - Association analysis of the chromosome 4p15-p16 candidate region for bipolar
      disorder and schizophrenia.
AB  - Several independent linkage studies have identified chromosome 4p15-p16 as a
      putative region of susceptibility for bipolar disorder (BP), schizophrenia (SCZ)
      and related phenotypes. Previously, we identified two subregions (B and D) of the
      4p15-p16 region that are shared by three of four 4p-linked families examined.
      Here, we describe a large-scale association analysis of regions B and D (3.8 and
      4.5 Mb, respectively). We selected 408 haplotype-tagging single nucleotide
      polymorphisms (SNPs) on a block-by-block basis from the International HapMap
      project and tested them in 368 BP, 386 SCZ and 458 control individuals. Nominal
      significance thresholds were determined using principal component analysis as
      implemented in the program SNPSpD. In region B, overlapping SNPs and haplotypes
      met the region-wide threshold (P<or=0.0005) at the global and individual
      haplotype test level and clustered in two regions. In region D, no individual
      SNPs were nominally significant, but multiple global and individual haplotypes
      were associated with BP and/or SCZ (region-wide threshold, P<or=0.0003). These
      overlapping haplotypes fell into two regions. Within each of these four clusters,
      at least one globally significant haplotype withstood permutation testing
      (P(gp)<or=0.05). Five predicted genes were found within these associated regions,
      while Known/RefSeq genes, including KIAA0746 and PPARGC1A, mapped nearby. There
      were also nine other clusters within regions B and D with nominally significant
      haplotypes, but only at the individual haplotype level. KIAA0746, PPARGC1A,
      GPR125, CCKAR and DKFZp761B107 overlapped with these regions. This study has
      identified significant associations between BP and SCZ within the chromosome 4p
      linkage region, resulting in candidate regions worthy of further investigation.

PMID- 17457314
TI  - Adult mice with reduced Nurr1 expression: an animal model for schizophrenia.
AB  - The transcription factor Nurr1 (NR4A2) has been found to play a critical role in
      the development of midbrain dopaminergic neurons. Nurr1 heterozygous (+/-) male
      and female mice expressing 35-40% of normal levels of Nurr1 were generated and
      examined in animal models related to symptoms of schizophrenia. The Nurr1 (+/-)
      mice displayed hyperactivity in a novel environment, which persisted after
      administration of the dopamine-mimetic amphetamine and the N-methyl-D-aspartate
      receptor antagonist phencyclidine. The Nurr1 (+/-) mice were deficient in the
      retention of emotional memory and showed an enhanced response to swim stress. In
      addition, Nurr1 (+/-) male mice displayed a reduced dopamine turnover in the
      striatum and an enhanced dopamine turnover in the prefrontal cortex, while female
      mice showed an opposite pattern. These results show that Nurr1 (+/-) mice display
      a pattern of behaviors indicative of potential relevance for symptoms of
      schizophrenia combined with a gender-specific abnormal dopamine transmission in
      the striatum and prefrontal cortex, respectively. This suggests that the Nurr1
      mutant mouse may be a potential animal model for studies on some of the
      behavioral and molecular mechanisms underlying schizophrenia.

PMID- 17457315
TI  - Arthroscopic lavage of the knee with or without corticosteroids versus joint
      aspiration--which is best?

PMID- 17457316
TI  - Should renal and bladder function be our compass for management of vesicoureteral
      reflux?

PMID- 17457318
TI  - Ras transformation mediates reovirus oncolysis by enhancing virus uncoating,
      particle infectivity, and apoptosis-dependent release.
AB  - Reovirus, a potential cancer therapy, replicates more efficiently in Ras
      transformed cells than in non-transformed cells. It was presumed that increased
      translation was the mechanistic basis of reovirus oncolysis. Analyses of each
      step of the reovirus life cycle now show that cellular processes deregulated by
      Ras transformation promote not one but three viral replication steps. First, in
      Ras-transformed cells, proteolytic disassembly (uncoating) of the incoming
      virions, required for onset of infection, occurs more efficiently. Consequently,
      threefold more Ras-transformed cells become productively infected with reovirus
      than non-transformed cells, which accounts for the observed increase of reovirus
      proteins in Ras-transformed cells. Second, Ras transformation increases the
      infectious-to-noninfectious virus particle ratio, as virions purified from Ras
      transformed cells are fourfold more infectious than those purified from non
      transformed cells. Progeny assembled in non- and Ras-transformed cells appear
      similar by electron microscopy and sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) analysis, suggesting that Ras transformation
      introduces a subtle change necessary for virus infectivity. Finally, reovirus
      release, mediated by caspase-induced apoptosis, is ninefold more efficient in Ras
      transformed cells. The combined effects of enhanced virus uncoating, infectivity,
      and release result in >100-fold differences in virus titers within one round of
      replication. Our analysis reveals previously unrecognized mechanisms by which Ras
      transformation mediates selective viral oncolysis.

PMID- 17457319
TI  - Correction of DNA protein kinase deficiency by spliceosome-mediated RNA trans
      splicing and sleeping beauty transposon delivery.
AB  - Spliceosome-mediated RNA trans-splicing (SMaRT) is an emerging technology for the
      repair of defective pre-messenger RNA (pre-mRNA) molecules. It is especially
      useful in the treatment of genetic disorders involving large genes. Although
      viral vectors have been used for achieving long-lasting expression of trans
      splicing molecules, the immunogenicity and suboptimal safety profiles associated
      with viral-based components could limit the widespread application of SMaRT in
      the repair of genetic defects. Here, we tested whether the non-viral Sleeping
      Beauty (SB) transposon system could mediate stable delivery of trans-splicing
      molecules designed to correct the genetic defect responsible for severe combined
      immune deficiency (SCID). This immunological disorder is caused by a point
      mutation within the 12.4 kilobase (kb) gene encoding the DNA protein kinase
      catalytic subunit (DNA-PKcs) and is associated with aberrant DNA repair,
      defective T- and B-cell production, and hypersensitivity to radiation-induced
      injury. Using a novel SB-based trans-splicing vector, we demonstrate stable mRNA
      correction, proper DNA-PKcs protein production, and conference of a radiation
      resistant phenotype in a T-cell thymoma cell line and SCID multipotent adult
      progenitor cells (MAPCs). These results suggest that SB-based trans-splicing
      vectors should prove useful in facilitating the correction of endogenous mutated
      mRNA transcripts, including the DNA-PKcs defect present in SCID cells.

PMID- 17457317
TI  - Advances in preclinical investigation of prostate cancer gene therapy.
AB  - Treating recurrent prostate cancer poses a great challenge to clinicians.
      Research efforts in the last decade have shown that adenoviral vector-based gene
      therapy is a promising approach that could expand the arsenal against prostate
      cancer. This maturing field is at the stage of being able to translate many
      preclinical discoveries into clinical practices. At this juncture, it is
      important to highlight the promising strategies including prostate-targeted gene
      expression, the use of oncolytic vectors, therapy coupled to reporter gene
      imaging, and combined treatment modalities. In fact, the early stages of clinical
      investigation employing combined, multimodal gene therapy focused on loco
      regional tumor eradication and showed promising results. Clinicians and
      scientists should seize the momentum of progress to push forward to improve the
      therapeutic outcome for the patients.

PMID- 17457320
TI  - Histone modifications are associated with the persistence or silencing of vector
      mediated transgene expression in vivo.
AB  - One of the major obstacles to success in non-viral gene therapy is
      transcriptional silencing of the DNA vector. The mechanisms underlying gene
      silencing/repression in mammalian cells are complex and remain unclear. Because
      changes in chromatin structure and, in particular, histone modifications are
      involved in transcriptional regulation of endogenous genes, we hypothesized that
      changes in the pattern of histone modifications were related to the observed
      transcriptional silencing of exogenous DNA vectors. We used antibodies against
      specific modified histones to perform chromatin immunoprecipitation (ChIP)
      analyses on liver lysates from mice transfected with two types of plasmids: (i)
      DNA minicircles (MCs) devoid of bacterial plasmid backbone DNA, which showed
      marked persistence of transgene expression, and (ii) their parental plasmids,
      which were silenced over time. Silencing of the transgene from the parental
      vectors was accompanied by an increase in heterochromatin-associated histone
      modifications and a decrease in modifications typically associated with
      euchromatin. Conversely, the pattern of histone modifications on the MC DNA was
      consistent with euchromatin. Our data indicates that (i) episomal vectors undergo
      chromatinization in vivo, and (ii) both persistence and silencing of transgene
      expression are associated with specific histone modifications.

PMID- 17457321
TI  - Cellular dynamics of EGF receptor-targeted synthetic viruses.
AB  - The epidermal growth factor receptor (EGFR) is overexpressed on a high percentage
      of human carcinomas. EGFR is an attractive therapeutic target for tissue-specific
      targeting by non-viral vectors in cancer gene therapy. In this study we analyzed
      and compared the effects of EGFR-targeted and untargeted polyplexes in respect to
      internalization into EGFR overexpressing HuH7 cells. Uptake kinetics and
      internalization dynamics were evaluated by flow cytometry and single-particle
      tracking. Our results clearly show that EGFR targeting leads to faster and more
      efficient internalization compared with untargeted particles. After 5 minutes 50%
      of the EGFR-targeted polyplexes were internalized, whereas untargeted polyplexes
      reached only approximately 20% internalization even after 20 minutes. In
      addition, single-particle tracking revealed a three-phase dynamics of the
      internalization process, and this was generally observed for polyplexes
      independent of targeting. Phase I was characterized by slow, actin cytoskeleton
      mediated movement of the particles with drift, and included the internalization
      process. During phase II particles displayed increased velocities with normal and
      confined diffusion in the cytoplasm. Phase III was characterized by fast active
      transport along microtubules. Targeting of polyplexes for receptor-mediated
      endocytosis by the EGFR resulted in shortening of phase I and strongly
      accelerated internalization.

PMID- 17457322
TI  - Bystander killing of malignant glioma by bone marrow-derived tumor-infiltrating
      progenitor cells expressing a suicide gene.
AB  - Adult stem cells are promising cellular vehicles for therapy of malignant gliomas
      as they have the ability to migrate into these tumors and even track infiltrating
      tumor cells. However, their clinical use is limited by a low passaging capacity
      that impedes large-scale production. In the present study, a bone marrow-derived,
      highly proliferative subpopulation of mesenchymal stem cells (MSCs)-here termed
      bone marrow-derived tumor-infiltrating cells (BM-TICs)-was genetically modified
      for the treatment of malignant glioma. Upon injection into the tumor or the
      vicinity of the tumor, BM-TICs infiltrated solid parts as well as the border of
      rat 9L glioma. After intra-tumoral injection, BM-TICs expressing the thymidine
      kinase of herpes simplex virus (HSV-tk) and enhanced green fluorescent protein
      (BM-TIC-tk-GFP) were detected by non-invasive positron emission tomography (PET)
      using the tracer 9-[4-[(18)F]fluoro-3-hydroxymethyl)butyl]guanine ([(18)F]FHBG).
      A therapeutic effect was demonstrated in vitro and in vivo by BM-TICs expressing
      HSV-tk through bystander-mediated glioma cell killing. Therapeutic efficacy was
      monitored by PET as well as by magnetic resonance imaging (MRI) and strongly
      correlated with histological analysis. In conclusion, BM-TICs expressing a
      suicide gene were highly effective in the treatment of malignant glioma in a rat
      model and therefore hold great potential for the therapy of malignant brain
      tumors in humans.

PMID- 17457323
TI  - Expert assessment of exposure to carcinogens in Norway's offshore petroleum
      industry.
AB  - This study presents and evaluates an expert group's assessment of exposure to
      carcinogens for defined job categories in Norway's offshore petroleum industry,
      1970-2005, to provide exposure information for a planned cohort study on cancer.
      Three university and five industry experts in occupational hygiene individually
      assessed the likelihood of exposure to 1836 combinations of carcinogens (n=17),
      job categories (n=27) and time periods (n=4). In subsequent plenary discussions,
      the experts agreed on exposed combinations. Agreement between the individual and
      the panel assessments was calculated by Cohen's kappa index. Using the panel
      assessment as reference, sensitivity and specificity were estimated. The eight
      experts assessed 63% of the 1836 combinations in plenary, resulting in 265 (14%)
      convened exposed combinations. Chlorinated hydrocarbons, benzene and inhalation
      of mineral oils had the highest number of exposed job categories (n=14, 9 and 10,
      respectively). The job categories classified as exposed to the highest numbers of
      carcinogens were the mechanics (n=10), derrick workers (n=6) and process
      technicians (n=5). The agreement between the experts' individual assessments and
      the panel assessment was kappa=0.53-0.74. The sensitivity was 0.55-0.86 and
      specificity 0.91-0.97. For these parameters, there were no apparent differences
      between the university experts and the industry experts. The resulting 265 of
      1836 possible exposure combinations convened as "exposed" by expert assessment is
      presented in this study. The experts' individual ratings highly agreed with the
      succeeding panel assessment. Correlation was found between years of experience of
      the raters and agreement with the panel. The university experts and the industry
      experts' assessments had no apparent differences. Further validation of the
      exposure assessment is suggested, such as by new sampling data or observational
      studies.

PMID- 17457324
TI  - The ECETOC approach to targeted risk assessment; lessons and experiences relevant
      to REACH.
AB  - ECETOC has been developed an approach by which the health and environmental risks
      arising from the supply and use of chemicals can be quickly and reliably
      evaluated by chemical suppliers. The approach has been available as a web-based
      tool since 2004. During the development and implementation of the approach,
      ECETOC has consulted widely so that the approach is seen to meet the required
      levels of science while also meeting the differing needs of affected
      stakeholders. The consultation process has yielded a number of findings in terms
      of the considerations necessary for implementing successful risk-informed
      decision-making in a multi-stakeholder environment. Concurrently, as the European
      Commission's REACH legislative package has begun to take shape, it has also
      become apparent that the approach has a number of potential applications for
      aiding the process of risk assessment under REACH. This paper reviews these
      experiences within the broader context of the expectations that REACH places on
      chemical manufacturers and suppliers. In particular, it highlights the key role
      that REACH Exposure Scenarios have for evaluating, managing and communicating
      chemical risks.

PMID- 17457326
TI  - Advertising and its discontents.

PMID- 17457327
TI  - Tubuloglomerular feedback responses of the downstream efferent resistance:
      unmasking a role for adenosine?
AB  - This Commentary aims to integrate or interrelate the available in vivo data with
      the in vitro study by Ren and co-workers, which comes to the somewhat surprising
      conclusion that tubuloglomerular feedback activation vasodilates the efferent
      arteriole by an adenosine-dependent mechanism.

PMID- 17457328
TI  - Diabetes: caught in the Akt?
AB  - One complication of diabetes is a pronounced renal cellular hypertrophy,
      inevitably resulting in chronic fibrotic changes. Chuang and colleagues
      demonstrate that hypertrophy in vitro is dependent on an increased
      phosphoinositide 3-kinase (PI3K) activity and is correlated with increased levels
      of p21(WAF1/Cip1), a cell-cycle regulator that was previously associated with
      renal fibrosis and sclerosis from nondiabetic causes.

PMID- 17457329
TI  - Membranous nephropathy: when and how to treat.
AB  - The treatment of idiopathic membranous nephropathy is heavily debated because of
      wide variation in outcome. A rational treatment strategy is needed to
      appropriately administer conservative treatment to the low-risk group but
      immunosuppressive therapy to those with medium or high risk of renal
      deterioration. Currently, combinations of steroids with alkylating agents are
      best studied. Newer forms of immunosuppressive treatment are currently under
      study.

PMID- 17457331
TI  - Hepato-renal confusion.

PMID- 17457333
TI  - Kidney International, false covers and loss of integrity.

PMID- 17457335
TI  - Osteodystrophy and dialysis survival.

PMID- 17457336
TI  - A large obstructive parapelvic cyst: challenging diagnosis and management.

PMID- 17457337
TI  - Purple urine bag syndrome in a hemodialysis patient.

PMID- 17457338
TI  - Measures of adiposity and body fat distribution in relation to serum folate
      levels in postmenopausal women in a feeding study.
AB  - OBJECTIVE: To assess the associations between serum folate concentration and
      measures of adiposity in postmenopausal women. DESIGN: This study was conducted
      as a cross-sectional analysis within the control segment of a randomized,
      crossover trial in which postmenopausal women (n=51) consumed 0 g (control), 15 g
      (one drink) and 30 g (two drinks) alcohol (ethanol)/day for 8 weeks as part of a
      controlled diet. Subjects in one treatment arm were crossed-over to another arm
      after a 2- to 5-week washout period. Body mass index (BMI) was measured, and dual
      energy X-ray absorptiometry (DEXA) scan administered to the women during the
      control (0 g alcohol) treatment, and a blood sample from this group was collected
      at baseline and week 8 of each diet period and analyzed for folate, B12,
      homocysteine and methylmalonic acid. SETTING: This study was conducted at the
      Beltsville Human Nutrition Research Center, MD, USA. RESULTS: In multivariate
      analysis, women who were overweight had a 12% lower, and obese women had a 22%
      lower serum folate concentrations compared to normal weight women (P-trend=0.02).
      Vitamin B12 also decreased with increasing BMI (P-trend=0.08). Increased BMI,
      percent body fat, and absolute amounts of central and peripheral fat were all
      significantly associated with decreased serum folate, but were unrelated to serum
      B12, homocysteine or methylmalonic acid. CONCLUSIONS: Our data show that
      adiposity is associated with lower serum folate levels in postmenopausal women.
      With obesity at epidemic proportions, these data, if confirmed by prospective or
      randomized controlled studies, have important public health implications.

PMID- 17457339
TI  - Location of body fat and body size impacts DXA soft tissue measures: a simulation
      study.
AB  - OBJECTIVE: The aim of this study was to determine the ability of dual X-ray
      absorptiometry (DXA) to detect exogenous fat in men and women simulating typical
      sex-specific weight changes. SUBJECTS: A diverse sample including 29 elderly (52
      83 years) and 61 young (18-40 years) individuals (45 women, 45 men) of varying
      body mass index (BMI; M+/-s.d.: 26.1+/-4.9 kg/m2, range=16.4-39 kg/m2). METHODS:
      Whole body (WB) DXA scans (Hologic QDR 4500A) were completed with Scan 1
      performed as a normal baseline scan, Scan 2 with 1 kg packet of lard placed on
      each thigh and Scan 3 with two 1 kg lard packets placed on the abdomen (men) or
      chest and abdomen (women). RESULTS: Measurement error of fat mass (FM) was more
      pronounced in the trunk as lard packets were detected with 59% accuracy
      (error=0.82+/-0.42 kg, P<0.001), whereas 94% of thigh lard (error=0.11+/-0.45 kg,
      P<0.001) was determined to be FM, while the remainder in both conditions was
      determined to be mineral free lean mass. Initial FM (r=0.37, P<0.001) for thigh
      loading and trunk bone mineral content (r=0.30, P<0.01) for trunk-loaded
      conditions had the most impact on measurement error of WB FM. CONCLUSIONS:
      Regional differences impact measurement error of simulated changes in FM with
      greater measurement error in the trunk compared to the thigh region and initial
      FM and higher levels of bone mineral content in the trunk region impacting error.

PMID- 17457340
TI  - Long-term effects of a plant-based dietary portfolio of cholesterol-lowering
      foods on blood pressure.
AB  - OBJECTIVE: To determine the effect on blood pressure of dietary advice to consume
      a combination of plant-based cholesterol-lowering foods (dietary portfolio).
      METHODS: For 1 year, 66 hyperlipidemic subjects were prescribed diets high in
      plant sterols (1.0 g/1000 kcal), soy protein (22.5 g/1000 kcal), viscous fibers
      (10 g/1000 kcal) and almonds (22.5 g/1000 kcal). There was no control group.
      Seven-day diet record, blood pressure and body weight were monitored initially
      monthly and later at 2-monthly intervals throughout the study. RESULTS: Fifty
      subjects completed the 1-year study. When the last observation was carried
      forward for non-completers (n=9) or those who changed their blood pressure
      medications (n=7), a small mean reduction was seen in body weight 0.7+/-0.3 kg
      (P=0.036). The corresponding reductions from baseline in systolic and diastolic
      blood pressure at 1 year (n=66 subjects) were -4.2+/-1.3 mm Hg (P=0.002) and 
      2.3+/-0.7 mm Hg (P=0.001), respectively. Blood pressure reductions occurred
      within the first 2 weeks, with stable blood pressures 6 weeks before and 4 weeks
      after starting the diet. Diastolic blood pressure reduction was significantly
      related to weight change (r=0.30, n=50, P=0.036). Only compliance with almond
      intake advice related to blood pressure reduction (systolic: r=-0.34, n=50,
      P=0.017; diastolic: r=-0.29, n=50, P=0.041). CONCLUSIONS: A dietary portfolio of
      plant-based cholesterol-lowering foods reduced blood pressure significantly,
      related to almond intake. The dietary portfolio approach of combining a range of
      cholesterol-lowering plant foods may benefit cardiovascular disease risk both by
      reducing serum lipids and also blood pressure.

PMID- 17457341
TI  - Methodology for studying postprandial lipid metabolism.
AB  - BACKGROUND: Postprandial lipid metabolism in humans has deserved much attention
      during the last two decades. Although fasting lipid and lipoprotein parameters
      reflect body homeostasis to some extent, the transient lipid and lipoprotein
      accumulation that occurs in the circulation after a fat-containing meal
      highlights the individual capacity to handle an acute fat input. An exacerbated
      postprandial accumulation of triglyceride-rich lipoproteins in the circulation
      has been associated with an increased cardiovascular risk. METHODS: The important
      number of studies published in this field raises the question of the methodology
      used for such postprandial studies, as reviewed. RESULTS: Based on our
      experiences, the present review reports and discuss the numerous methodological
      issues involved to serve as a basis for further works. These aspects include aims
      of the postprandial tests, size and nutrient composition of the test meals and
      background diets, pre-test conditions, characteristics of subjects involved,
      timing of sampling, suitable markers of postprandial lipid metabolism and
      calculations. CONCLUSION: In conclusion, we stress the need for standardization
      of postprandial tests.

PMID- 17457342
TI  - Megalin genetic polymorphisms and individual sensitivity to the ototoxic effect
      of cisplatin.
AB  - Ototoxicity and nephrotoxicity are dose-limiting side effects of cisplatin.
      Megalin, a member of the low-density lipoprotein receptor family, is highly
      expressed in renal proximal tubular cells and marginal cells of the stria
      vascularis of the inner ear - tissues, which accumulate high levels of platinum
      DNA adducts. On the assumption that the mechanisms of cisplatin-induced nephro-
      and ototoxicity involve megalin we analyzed the incidence of the non-synonymous
      single nucleotide polymorphisms (SNP) rs2075252 and rs4668123 in 25 patients who
      developed a distinct hearing loss during cisplatin therapy and in 25 patients
      without hearing impairment after cisplatin therapy. We found no association
      between cisplatin-induced ototoxicity and any allele of rs4668123 but observed a
      higher frequency of the A-allele of rs2075252 in the group with hearing
      impairment than in the group with normal hearing after cisplatin therapy (0.32
      versus 0.14) (chi(2)=5.83, P<0.02; odds ratio: 3.45; 95% confidence interval:
      1.11-11.2) indicating that SNPs at the megalin gene might impact the individual
      susceptibility against cisplatin-induced ototoxicity.

PMID- 17457343
TI  - The family of five: TIR-domain-containing adaptors in Toll-like receptor
      signalling.
AB  - Signalling by Toll-like receptors (TLRs) involves five adaptor proteins known as
      MyD88, MAL, TRIF, TRAM and SARM. Recent insights have revealed additional
      functions for MyD88 apart from NF-kappaB activation, including activation of the
      transcription factors IRF1, IRF5 and IRF7, and also a role outside the TLRs in
      interferon-gamma signalling. Biochemical information on MAL and TRAM has shown
      that both act as bridging adaptors, with MAL recruiting MyD88 to TLR2 and TLR4,
      and TRAM recruiting TRIF to TLR4 to allow for IRF3 activation. Finally, the
      function of the fifth adaptor, SARM, has been revealed, which negatively
      regulates TRIF. These new insights allow for a detailed description of the
      function of the five TIR-domain-containing adaptors in the initiation of TLR
      signalling.

PMID- 17457344
TI  - Innate immunity of the newborn: basic mechanisms and clinical correlates.
AB  - The fetus and newborn face a complex set of immunological demands, including
      protection against infection, avoidance of harmful inflammatory immune responses
      that can lead to pre-term delivery, and balancing the transition from a sterile
      intra-uterine environment to a world that is rich in foreign antigens. These
      demands shape a distinct neonatal innate immune system that is biased against the
      production of pro-inflammatory cytokines. This bias renders newborns at risk of
      infection and impairs responses to many vaccines. This Review describes innate
      immunity in newborns and discusses how this knowledge might be used to prevent
      and treat infection in this vulnerable population.

PMID- 17457345
TI  - Immune evasion by Kaposi's sarcoma-associated herpesvirus.
AB  - To efficiently establish a persistent infection, Kaposi's sarcoma-associated
      herpesvirus (KSHV; also known as HHV8) dedicates a large amount of its coding
      potential to produce proteins that antagonize the immune system of its host.
      These viral immunomodulators interfere with both the innate and adaptive immune
      responses and most of them are homologous to cellular proteins, suggesting that
      they have been pirated from the host during viral evolution. In this Review, I
      present recent advances in the understanding of immune evasion by KSHV, with a
      particular focus on the virally encoded modulators of immune responses that are
      unique to this virus.

PMID- 17457346
TI  - Rethinking peptide supply to MHC class I molecules.
AB  - The notion that peptides bound to MHC class I molecules are derived mainly from
      newly synthesized proteins that are defective, and are therefore targeted for
      immediate degradation, has gained wide acceptance. This model, still entirely
      hypothetical, has strong intuitive appeal and is consistent with some
      experimental results, but it is strained by other findings, as well as by
      established and emerging concepts in protein quality control. While not
      discounting defectiveness as a driving force for the processing of some proteins,
      we propose that MHC-class-I-restricted epitopes are derived mainly from nascent
      proteins that are accessed by the degradation machinery prior to any assessment
      of fitness, and we outline one way in which this could be accomplished.

PMID- 17457347
TI  - Women and heart disease: time for change.

PMID- 17457348
TI  - 'End-stage' hypertrophic cardiomyopathy: from mystery to model.

PMID- 17457349
TI  - Calcific aortic stenosis: an update.
AB  - Calcific aortic stenosis in the elderly is the number one cause of surgical valve
      replacement in the US and Europe. The incidence of calcific aortic stenosis is
      increasing as the general age of the population increases. For many years,
      rheumatic heart disease was the main cause of aortic valve disease. Over the last
      half century, however, there has been a change from a rheumatic etiology to a
      'degenerative' mechanism because of the increase in access to health care in
      developed countries and the increasing age of the population in the US and
      Europe. For many years 'degenerative' aortic stenosis was thought to be caused by
      the passive accumulation of calcium on the surface of the aortic valve leaflet.
      Recent studies have demonstrated, however, that the etiology of aortic valve
      disease has a similar pathophysiology to that of vascular atherosclerosis, and
      that the treatment of this disease could be similar to that of chronic vascular
      atherosclerosis. This Review will discuss our current understanding of the
      pathophysiology, risk factors, cellular mechanisms, diagnosis and finally, future
      medical therapies for calcific aortic stenosis.

PMID- 17457350
TI  - The erectile-endothelial dysfunction nexus: new opportunities for cardiovascular
      risk prevention.
AB  - Erectile and endothelial dysfunction are common in individuals with multiple
      cardiovascular risk factors and are longitudinal predictors of cardiovascular
      events. The pathogenesis of both endothelial and erectile dysfunction is
      intimately linked through increased expression and activation of endothelial
      nitric oxide synthase, and the subsequent physiological actions of nitric oxide.
      Endothelial production of nitric oxide by endothelial nitric oxide synthase in
      the corpus cavernosum is involved in the maintenance of penile erection. Erectile
      dysfunction can be detected clinically using systematic questioning and could
      potentially be employed as an independent predictor of cardiovascular risk to
      target treatment of cardiovascular risk factors. Both erectile and endothelial
      dysfunction respond to lifestyle modifications, particularly in individuals with
      the metabolic syndrome. Drugs that improve endothelial dysfunction can also
      improve erectile dysfunction, but responses are not always concordant.
      Phosphodiesterase type 5 inhibitors, however, are powerful agents that commonly
      improve erectile and endothelial dysfunction, with potential cardiac
      applications. The recent Princeton consensus requires more extensive
      implementation and evaluation in clinical practice. The judicious diagnosis of
      erectile dysfunction, nevertheless, provides a unique opportunity for the
      prevention of cardiovascular disease.

PMID- 17457351
TI  - Mechanisms of disease: L-arginine in coronary atherosclerosis--a clinical
      perspective.
AB  - L-arginine is the substrate of endothelial nitric oxide synthase and the main
      precursor of nitric oxide in the vascular endothelium, thus its effects are
      mediated largely by increases in nitric oxide production. L-arginine has
      antioxidant and antiapoptotic properties, increases smooth muscle relaxation,
      inhibits the expression of adhesion molecules and chemotactic peptides, decreases
      endothelin-1 expression, and inhibits platelet aggregation. This amino acid also
      improves endothelial function in patients with coronary artery disease and
      dilates human epicardial atheromatous coronary arteries. Despite the positive
      results from small case-control studies, it is still unclear whether chronic
      administration of L-arginine has any effect on clinical outcome in patients with
      coronary artery disease. In addition, other indirect strategies, such as the
      inhibition of arginase, could prove more effective at improving intracellular L
      arginine bioavailability than exogenous L-arginine administration. The potential
      clinical usefulness of L-arginine, therefore, needs further evaluation in large,
      prospective clinical trials. Here, we present a critique of the existing
      literature about the role of L-arginine in the prevention of atherosclerosis.

PMID- 17457352
TI  - Ventricular ectopy during REM sleep: implications for nocturnal sudden cardiac
      death.
AB  - BACKGROUND: A young adult female presented with syncope and periodic weakness. A
      12-lead electrocardiogram showed frequent premature ventricular contractions and
      prolonged QU interval. Repetitive runs of nonsustained ventricular tachycardia
      were recorded at night. INVESTIGATIONS: Electromyography, muscle biopsy, MRI,
      echocardiography, exercise stress testing using Bruce protocol with microvolt T
      wave alternans testing, 24 h Holter monitoring, electrophysiological testing and
      examination of the effects of sleep and sleep stage on the patient's ventricular
      arrhythmias. DIAGNOSIS: Type 1 Andersen-Tawil syndrome, (also known as type 7
      long QT syndrome). Severe ventricular arrhythmia was observed, predominantly
      during rapid eye movement sleep. We speculate that the autonomic instability
      present during rapid eye movement sleep precipitates increasing vulnerability to
      sleep-related ventricular tachycardia. MANAGEMENT: Beta-blocker therapy alone,
      subsequently combined with mexiletine treatment.

PMID- 17457357
TI  - What new drugs can nephrologists look forward to in the next year or two?

PMID- 17457358
TI  - When should patients with ANCA-associated vasculitis be switched from induction
      to maintenance therapy?

PMID- 17457359
TI  - Central venous catheter-related bacteremia in chronic hemodialysis patients:
      epidemiology and evidence-based management.
AB  - Central venous catheter-related blood stream infection (CRBSI) is a major cause
      of morbidity and mortality in patients with end-stage renal disease treated with
      chronic hemodialysis. Risk factors include Staphylococcus aureus nasal
      colonization, longer duration of catheter use, previous bacteremia, older age,
      higher total intravenous iron dose, lower hemoglobin and serum albumin levels,
      diabetes mellitus and recent hospitalization. Symptoms that raise clinical
      suspicion of bacteremia in chronic hemodialysis patients are fevers and chills.
      When CRBSI is suspected, blood cultures should be obtained and empirical therapy
      with broad spectrum intravenous antibiotics initiated. The diagnosis of CRBSI is
      confirmed by isolation of the same microorganism from quantitative cultures of
      both the catheter and the peripheral blood of a patient that has clinical
      features of infection without any other apparent source. Gram-positive cocci,
      predominantly S. epidermidis and S. aureus, cause bacteremia in two-thirds of
      cases. Among the various approaches to management of CRBSI, removal and delayed
      replacement of the catheter, catheter exchange over a guidewire in selected
      patients, and the use of antimicrobial/citrate lock solutions have all been found
      to be promising for treatment and/or prevention; however, resolution of issues
      regarding selection, dose, duration and emergence of antibiotic-resistant
      organisms with chronic use of antibiotic lock solutions, as well as the safety of
      long-term use of trisodium citrate lock solutions, await further randomized,
      multicenter trials involving larger samples of hemodialysis patients.

PMID- 17457360
TI  - Technology insight: artificial extracorporeal liver support--how does Prometheus
      compare with MARS?
AB  - Artificial extracorporeal liver support or 'liver dialysis' has been used in
      patients with severe liver failure with increasing frequency since the Molecular
      Adsorbents Recirculating System (MARS), a variant of albumin dialysis, was
      introduced in 1999. Nevertheless, liver dialysis must still be thought of as
      experimental because its contribution to improved patient survival has not been
      proven in large randomized trials. Prometheus is a novel device for fractionated
      plasma separation via an albumin-permeable filter that was developed to improve
      removal of albumin-bound toxins. Initial studies have proven clinical use of
      Prometheus to be feasible and safe. Head-to-head comparisons of Prometheus and
      MARS have shown treatment with the former to be more efficient with respect to
      removal of most albumin-bound and water-solved markers. As controlled studies
      with clinical end points are lacking, it is not known whether the observed
      greater detoxification capacity of Prometheus will translate into clinical
      benefit; two small studies indicate that there might be a beneficial effect in
      hepatic encephalopathy and pruritus. In a recent randomized comparison of MARS
      and Prometheus, however, hemodynamic improvement was observed in response to
      MARS, but not Prometheus, treatment. A large randomized controlled trial
      investigating the effect of Prometheus on survival--the HELIOS study--has been
      initiated. First results are expected in 2008 and will be crucial to establishing
      a role for Prometheus in the field of extracorporeal liver support.

PMID- 17457361
TI  - Mechanisms of disease: the complement system in renal injury--new ways of looking
      at an old foe.
AB  - The fact that the complement system is activated during immune-complex glomerular
      disease has been known for nearly 50 years. Detection of complement deposition in
      the glomerulus using immunochemistry has become an important element of the
      histological analysis of renal biopsies, and is key to the diagnosis of many
      types of glomerulonephritis. In recent years it has become evident that
      complement activation is involved in the pathogenesis of other types of renal
      disease; complement activation is implicated in transplant injury, atypical
      hemolytic uremic syndrome and progressive tubulointerstitial fibrosis. Emergence
      of this evidence has provided insight into how these diseases develop, and has
      yielded useful diagnostic tools and potential targets for therapeutic
      intervention. Clinicians have, by using plasma-based therapies, unknowingly
      treated abnormalities of the complement system in renal patients for many years.
      Advances in antibody and protein technologies have led to the development of
      complement inhibitors that have been used in phase III clinical studies. More
      specific agents and applications are likely to be developed over the coming years
      and are discussed in this Review.

PMID- 17457362
TI  - Proteinuria in a patient receiving anti-VEGF therapy for metastatic renal cell
      carcinoma.
AB  - BACKGROUND: A 59-year-old man who had undergone a left nephrectomy for renal cell
      carcinoma was found to have metastatic disease during a restaging examination.
      The patient was started on treatment with interferon alpha2b plus bevacizumab, a
      humanized monoclonal anti-vascular endothelial growth factor antibody. After 9
      months of this therapy, the patient developed proteinuria, which gradually
      increased to over 6 g/day. INVESTIGATIONS: Physical examination, urine and blood
      analysis, biopsy of the right kidney, and histologic evaluation of the non
      neoplastic portion of the left nephrectomy specimen. DIAGNOSIS: Thrombotic
      microangiopathy and IgA immune-complex deposition in the glomerular capillary
      walls and mesangium. MANAGEMENT: Discontinuation of interferon alpha2b and
      bevacizumab, control of blood pressure with an angiotensin-converting-enzyme
      inhibitor and an angiotensin-receptor blocker.

PMID- 17457363
TI  - Increased expression of a proline-rich Akt substrate (PRAS40) in human
      copper/zinc-superoxide dismutase transgenic rats protects motor neurons from
      death after spinal cord injury.
AB  - The serine-threonine kinase, Akt, plays an important role in the cell survival
      signaling pathway. A proline-rich Akt substrate, PRAS40, has been characterized,
      and an increase in phospho-PRAS40 (pPRAS40) is neuroprotective after transient
      focal cerebral ischemia. However, the involvement of PRAS40 in the cell
      death/survival pathway after spinal cord injury (SCI) is unclear. Liposome
      mediated PRAS40 transfection was performed to study whether overexpression of
      pPRAS40 is neuroprotective. We further examined the expression of pPRAS40 after
      SCI by immunohistochemistry and Western blot using copper/zinc-superoxide
      dismutase (SOD1) transgenic (Tg) rats and wild-type (Wt) littermates. We then
      examined the relationship between PRAS40 and Akt by injection of LY294002, a
      phosphatidylinositol 3-kinase (PI3K) pathway inhibitor, or Akt inhibitor IV, a
      compound that inhibits Akt activation after SCI. Our data demonstrated that
      increased pPRAS40 resulted in survival of more motor neurons compared with
      control complementary DNA transfection. Phosphorylated PRAS40 increased in the Wt
      rats after SCI, whereas there was a greater and prolonged increase in the SOD1 Tg
      rats. Coimmunoprecipitation showed that binding of pPRAS40 with 14-3-3 increased
      1 day after SCI in the Wt rats, whereas there was a significant increase in the
      Tg rats. The inhibitor studies showed that phospho-Akt and pPRAS40 were decreased
      after injection of LY294002 or Akt inhibitor IV. We conclude that an increase in
      pPRAS40 by transfection after SCI results in survival of motor neurons, and
      overexpression of SOD1 in the Tg rats results in an increase in endogenous
      pPRAS40 and a decrease in motor neuron death through the PI3K/Akt pathway.

PMID- 17457364
TI  - Imaging brain inflammation with [(11)C]PK11195 by PET and induction of the
      peripheral-type benzodiazepine receptor after transient focal ischemia in rats.
AB  - [(11)C]PK11195 is used in positron emission tomography (PET) studies for imaging
      brain inflammation in vivo as it binds to the peripheral-type benzodiazepine
      receptor (PBR) expressed by reactive glia and macrophages. However, features of
      the cellular reaction required to induce a positive [(11)C]PK11195 signal are not
      well characterized. We performed [(11)C]PK11195 PET and autoradiography in rats
      after transient focal cerebral ischemia. We determined [(3)H]PK11195 binding and
      PBR expression in brain tissue and examined the lesion with several markers.
      [(11)C]PK11195 standard uptake value increased at day 4 and grew further at day 7
      within the ischemic core. Accordingly, ex vivo [(3)H]PK11195 binding increased at
      day 4, and increases further at day 7. The PET signal also augmented in
      peripheral regions, but to a lesser extent than in the core. Binding in the
      region surrounding infarction was supported by [(11)C]PK11195 autoradiography at
      day 7 showing that the radioactive signal extended beyond the infarcted core.
      Enhanced binding was preceded by increases in PBR mRNA expression in the
      ipsilateral hemisphere, and a 18-kDa band corresponding to PBR protein was
      detected. Peripheral-type benzodiazepine receptor immunohistochemistry showed
      subsets of ameboid microglia/macrophages within the infarcted core showing a
      distinctive strong PBR expression from day 4. These cells were often located
      surrounding microhemorrhages. Reactive astrocytes forming a rim surrounding
      infarction at day 7 also showed some PBR immunostaining. These results show
      cellular heterogeneity in the level of PBR expression, supporting that PBR is not
      a simple marker of inflammation, and that the extent of [(11)C]PK11195 binding
      depends on intrinsic features of the inflammatory cells.

PMID- 17457365
TI  - Downregulation of hippocampal adenosine kinase after focal ischemia as potential
      endogenous neuroprotective mechanism.
AB  - The rate of ischemic brain injury varies with the brain region, requiring only
      hours in striatum but days in hippocampus. Such maturation implies the existence
      of endogenous neuroprotective mechanisms. Adenosine is an endogenous
      neuroprotectant regulated by adenosine kinase (ADK). To investigate, whether
      adenosine might play a role in protecting the hippocampus after focal ischemia,
      we subjected transgenic mice, which overexpress ADK in hippocampal neurons (Adk
      tg mice) to transient middle cerebral artery occlusion (MCAO). Although the
      hippocampus of wild-type (wt) mice was consistently spared from injury after 60
      mins of MCAO, hippocampal injury became evident in Adk-tg mice after only 15 mins
      of MCAO. To determine, whether downregulation of hippocampal ADK might qualify as
      candidate mechanism mediating endogenous neuroprotection, we evaluated ADK
      expression in wt mice after several periods of reperfusion after 15 or 60 mins of
      MCAO. After 60 mins of MCAO, hippocampal ADK was significantly reduced in both
      hemispheres after 1, 3, and 24 h of reperfusion. Reduction of ADK
      immunoreactivity corresponded to a 2.2-fold increase in hippocampal adenosine at
      3 h of reperfusion. Remarkably, a significant reduction of ADK immunoreactivity
      was also found in the ipsilateral (stroked) hippocampus after 15 mins of MCAO and
      3 h of reperfusion. Thus, transient downregulation of hippocampal ADK after
      stroke might be a protective mechanism during maturation hippocampal cell loss.

PMID- 17457366
TI  - Reduced tissue damage and improved recovery of motor function after traumatic
      brain injury in mice deficient in complement component C4.
AB  - Complement component C4 mediates C3-dependent tissue damage after systemic
      ischemia-reperfusion injury. Activation of C3 also contributes to the
      pathogenesis of experimental and human traumatic brain injury (TBI); however, few
      data exist regarding the specific pathways (classic, alternative, and lectin)
      involved. Using complement knockout mice and a controlled cortical impact (CCI)
      model, we tested the hypothesis that the classic pathway mediates secondary
      damage after TBI. After CCI, C4c and C3d immunostaining were detected in cortical
      vascular endothelial cells in wild-type (WT) mice; however, C4c and C3d
      immunostaining were also detected in C1q(-/-) mice, and C3d immunostaining was
      detected in C4(-/-) mice. After CCI, WT and C1q(-/-) mice had similar motor
      deficits, Morris water maze performance, and brain lesion size. Naive C4(-/-) and
      WT mice did not differ in baseline motor performance, but C4(-/-) mice had
      reduced postinjury motor deficits (days 1 to 7, P<0.05) and decreased brain
      tissue damage (days 14 and 35, P<0.05) versus WT. Reconstitution of C4(-/-) mice
      with human C4 (hC4) reversed their protection against postinjury motor deficits
      (P<0.05 versus vehicle), but administration of hC4 did not impair postinjury
      motor performance (versus vehicle) in WT mice. The protective effects of C4(-/-)
      were functionally distinct from the classic pathway and terminal complement, as
      C1q(-/-) and C3(-/-) mice had postinjury tissue damage and motor dysfunction
      similar to WT. Thus, C4 contributes to motor deficits and brain tissue damage
      after CCI by mechanism(s) fundamentally different from those involved in
      experimental systemic ischemia-reperfusion injury.

PMID- 17457367
TI  - A neuroprotective function for the hematopoietic protein granulocyte-macrophage
      colony stimulating factor (GM-CSF).
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic
      cytokine responsible for the proliferation, differentiation, and maturation of
      cells of the myeloid lineage, which was cloned more than 20 years ago. Here we
      uncovered a novel function of GM-CSF in the central nervous system (CNS). We
      identified the GM-CSF alpha-receptor as an upregulated gene in a screen for
      ischemia-induced genes in the cortex. This receptor is broadly expressed on
      neurons throughout the brain together with its ligand and induced by ischemic
      insults. In primary cortical neurons and human neuroblastoma cells, GM-CSF
      counteracts programmed cell death and induces BCL-2 and BCL-Xl expression in a
      dose- and time-dependent manner. Of the signaling pathways studied, GM-CSF most
      prominently induced the PI3K-Akt pathway, and inhibition of Akt strongly
      decreased antiapoptotic activity. Intravenously given GM-CSF passes the blood
      brain barrier, and decreases infarct damage in two different experimental stroke
      models (middle cerebral artery occlusion (MCAO), and combined common
      carotid/distal MCA occlusion) concomitant with induction of BCL-Xl expression.
      Thus, GM-CSF acts as a neuroprotective protein in the CNS. This finding is
      remarkably reminiscent of the recently discovered functionality of two other
      hematopoietic factors, erythropoietin and granulocyte colony-stimulating factor
      in the CNS. The identification of a third hematopoietic factor acting as a
      neurotrophic factor in the CNS suggests a common principle in the functional
      evolution of these factors. Clinically, GM-CSF now broadens the repertoire of
      hematopoietic factors available as novel drug candidates for stroke and
      neurodegenerative diseases.

PMID- 17457368
TI  - Estimating the odds ratios of Crohn disease for the main CARD15/NOD2 mutations
      using a conditional maximum likelihood method in pedigrees collected via affected
      family members.
AB  - Estimation of genotype-specific risks at a disease susceptibility locus is an
      important question that is best carried out in a prospective study. Nevertheless
      it is usually desirable to make use of data from the families that have already
      been collected to identify the susceptibility locus. Assuming that the families
      have been collected without regard to genotype at the locus in question, most of
      the information can be extracted by writing the likelihood in terms of the risk
      for a genotype relative to the standard genotype and conditional on the parental
      mating type. Parameters may then be estimated by explicit solution of likelihood
      equations. This method permits estimation of risks for heterozygotes and
      homozygotes for different alleles, testing of different modes of inheritance and
      heterogeneity of risk between alleles. It is applicable to risk alleles for any
      disease locus or incompletely penetrant phenotype. We have used the method to
      estimate risks of Crohn disease for different CARD/NOD2 15 mutations, using the
      families originally collected to identify this susceptibility locus. The odds
      ratio of Crohn disease were, respectively, 1.97+/-0.85, 3.05+/-* and 4.55+/-1.34
      for the R702W, G9068R and 1007fs heterozygotes and 3.29+/-0.64, 12.13+/-* and
      34.66+/-12.87 for the corresponding homozygotes. (* Signifies insufficient data
      to estimate these values.) These results confirm the dosage effect for
      CARD15/NOD2 mutations and demonstrate that the disease risks are very different
      in homozygotes. This last observation illustrates the power of this approach,
      especially for alleles with low or moderate frequency in the general population.

PMID- 17457369
TI  - Genotypic and haplotypic associations of the DBH gene with plasma dopamine beta
      hydroxylase activity in African Americans.
AB  - Several variants at DBH are significantly associated with plasma DbetaH activity
      (pDbetaH). However, the overwhelming majority of data on this genotype-phenotype
      relationship has been gathered in samples from Europeans and European Americans
      (EAs). In this study, we examined the relationship between DBH polymorphisms and
      pDbetaH in samples from African-American (AA) subjects. Genotypes were determined
      at a 19-bp insertion/deletion polymorphism (ins/del) and four single-nucleotide
      polymorphisms (SNPs) at DBH in 109 samples. Analyses were performed using
      analyses of variance (ANOVAs) (for individual SNPs) and regression procedures (to
      assess the joint effects and the specific SNP-based haplotypes). We found: (1)
      single-variant analysis of all polymorphisms revealed apparent associations to
      pDbetaH, with rs1611115 accounting for the largest proportion of the variance in
      pDbetaH (28.7%) and ins/del the smallest (6.5%); (2) modest but significant
      linkage disequilibrium (LD) existed between ins/del and rs1611115; (3) LD between
      all other pairs of variants was not observed; (3) stepwise regression showed that
      a model containing rs1611115, rs2519152 and rs6271 accounted for 37.6% of the
      variance in pDbetaH, with rs6271 showing additional 7.6% above the effect of
      rs1611115, and rs2519152 showing additional 2% above rs1611115 and rs6271; (4)
      two common haplotypes, C-T-C and T-C-C at rs1611115-rs2519152-rs6271 were
      significantly associated with pDbetaH (P=0.0025 and 0.0036, respectively). The
      data support the validity of prior reported associations and underscore the
      importance of analyzing multiple SNPs across DBH in future association studies
      examining disease and biochemical phenotypes.

PMID- 17457370
TI  - Transgenerational response to nutrition, early life circumstances and longevity.
AB  - Nutrition might induce, at some loci, epigenetic or other changes that could be
      transmitted to the next generation impacting on health. The slow growth period
      (SGP) before the prepubertal peak in growth velocity has emerged as a sensitive
      period where different food availability is followed by different
      transgenerational response (TGR). The aim of this study is to investigate to what
      extent the probands own childhood circumstances are in fact the determinants of
      the findings. In the analysis, data from three random samples, comprising 271
      probands and their 1626 parents and grandparents, left after exclusions because
      of missing data, were utilized. The availability of food during any given year
      was classified based on regional statistics. The ancestors' SGP was set at the
      ages of 8-12 years and the availability of food during these years classified as
      good, intermediate or poor. The probands' childhood circumstances were defined by
      the father's ownership of land, the number of siblings and order in the sibship,
      the death of parents and the parents' level of literacy. An earlier finding of a
      sex-specific influence from the ancestors' nutrition during the SGP, going from
      the paternal grandmother to the female proband and from the paternal grandfather
      to the male proband, was confirmed. In addition, a response from father to son
      emerged when childhood social circumstances of the son were accounted for. Early
      social circumstances influenced longevity for the male proband. TGRs to
      ancestors' nutrition prevailed as the main influence on longevity.

PMID- 17457371
TI  - Podocyte protection by darbepoetin: preservation of the cytoskeleton and nephrin
      expression.
AB  - Podocyte injury is a significant contributor to proteinuria and
      glomerulosclerosis. Recent studies have shown a renoprotective effect of
      erythropoietin (EPO) during ischemic kidney disease. In this study, we examine
      mechanisms by which a long acting recombinant EPO analog, darbepoetin, may confer
      renoprotection in the puromycin aminonucleoside-induced model of nephrotic
      syndrome. Darbepoetin decreased the proteinuria of rats treated with puromycin.
      This protective effect was correlated with the immunohistochemical disappearance
      of the podocyte injury markers desmin and the immune costimulator molecule B7.1
      with the reappearance of nephrin expression in the slit diaphragm. Podocyte foot
      process retraction and effacement along with actin filament rearrangement,
      determined by electron microscopy, were all reversed by darbepoetin treatment.
      The protective effects were confirmed in puromycin-induced nephrotic rats that
      had been hemodiluted to normal hematocrit levels. Furthermore, puromycin
      treatment of rat podocytes in culture caused actin cytoskeletal reorganization
      along with deranged nephrin distribution. All these effects in vitro were
      reversed by darbepoetin. Our study demonstrates that darbepoetin treatment
      ameliorates podocyte injury and decreases proteinuria by a direct effect on
      podocytes. This may be accomplished by maintenance of the actin cytoskeleton and
      nephrin expression.

PMID- 17457372
TI  - The endothelium-derived hyperpolarizing factor: insights from genetic animal
      models.
AB  - In the late eighties, several studies revealed the existence of a third
      vasodilating factor next to nitric oxide (NO) and prostacyclin (PGI2). As the
      action of this third factor is closely related to smooth muscle
      hyperpolarization, this factor was termed endothelium-derived hyperpolarizing
      factor (EDHF). The story of its investigation is a confusing one and several
      different candidate molecules and pathways have been proposed to account for the
      EDHF phenomenon. Major candidate molecules/mediators of EDHF signalling are K+,
      electrical coupling through gap junctions, cytochrome P450 metabolites, and
      endothelial small- and intermediate Ca2+-activated K+ channels (SK(Ca) and
      IK(Ca)). In this mini review, we wish to convey that EDHF is as powerful as NO
      and PGI2 in terms of blood pressure regulation and that deficiency in EDHF
      signalling contribute to several cardiovascular pathologies such as hypertension,
      chronic renal failure, and diabetes. In addition, we focus on recent insight into
      the EDHF phenomenon provided by novel genetic animal models, such as mice
      deficient of either endothelial SK(Ca) or IK(Ca) and the impact of channel
      deficiency on endothelial function, EDHF signalling, and arterial blood pressure.

PMID- 17457373
TI  - Early changes in gene expression that influence the course of primary glomerular
      disease.
AB  - Serial changes in glomerular capillary loop gene expression were used to uncover
      mechanisms contributing to primary glomerular disease in rat models of passive
      Heymann nephritis and puromycin nephrosis. Before the onset of proteinuria,
      podocyte protein-tyrosine phosphatase (GLEPP1) expression was transiently
      decreased in the nephrosis model, whereas the immune costimulatory molecule B7.1
      was stimulated in both models. To relate these changes to the development of
      proteinuria, the time of onset and intensity of proteinuria were altered. When
      the models were induced simultaneously, proteinuria and anasarca occurred earlier
      with the collapse of glomerular capillary loops. Upregulation of B7.1 with the
      downregulation of GLEPP1, Wilms' tumor gene (WT1), megalin, and vascular
      endothelial growth factor started early and persisted through the course of
      disease. In the puromycin and the combined models, changes in GLEPP1 expression
      were corticosteroid-sensitive, whereas B7.1, WT1, vascular endothelial growth
      factor, and most slit diaphragm genes involved later in the combined model,
      except podocin, were corticosteroid-resistant. There was a very early increase in
      the nuclear expression of podocyte transcription factors ZHX2 and ZHX1 that may
      be linked to the changes in gene expression in the combined proteinuric model.
      Our studies suggest that an early and persistent change in mostly steroid
      resistant glomerular gene expression is the hallmark of severe and progressive
      glomerular disease.

PMID- 17457374
TI  - Fever, nephrotic syndrome, and rapidly progressive renal failure.

PMID- 17457375
TI  - Gentamicin-induced ototoxicity in hemodialysis patients is ameliorated by N
      acetylcysteine.
AB  - Aminoglycoside (AG) antibiotics are associated with several side effects,
      including a reversible nephrotoxicity and a permanent ototoxicity. Oxidative
      stress is thought to contribute to the pathophysiology of both conditions. We
      studied the possible protective effect of the antioxidant N-acetylcysteine (NAC)
      in gentamicin-induced hearing loss in hemodialysis patients. This study includes
      53 hemodialysis patients scheduled to receive gentamicin for dialysis catheter
      related bacteremia that were randomized to receive the antibiotic with or without
      NAC. Hearing function was assessed by the standard technique of pure-tone
      audiograms over a range of frequencies. Audiometric evaluations were performed at
      baseline, 1 week and at 6 weeks after the completion of gentamicin therapy. A
      total of 40 patients completed the study protocol with a mean duration of therapy
      of almost 15 days. At both 1 and 6 weeks after the completion of antibiotic
      therapy, there were significantly more patients exhibiting ototoxicity in the
      control group compared with the group receiving NAC. Additionally, significantly
      more patients in the control group had bilateral ototoxicity. The greatest
      otoprotective effect of NAC was noticed in the high audiometric tone frequencies.
      Taken together, our study suggests that NAC treatment may ameliorate gentamicin
      induced ototoxicity in hemodialysis patients.

PMID- 17457376
TI  - Intestinal phosphate absorption in a model of chronic renal failure.
AB  - Hyperphosphatemia is an important consequence of chronic renal failure (CRF).
      Lowering of the plasma phosphate concentration is believed to be critical in the
      management of patients with CRF, especially those on dialysis. Reports of the
      effect of CRF on the intestinal handling of phosphate in vitro have been
      conflicting; but what happens in vivo has not been studied. What effect a
      reduction in the dietary phosphate intake has on intestinal phosphate absorption
      in CRF in vivo is unclear. In this study, we have used the in situ intestine loop
      technique to determine intestinal phosphate absorption in the 5/6-nephrectomy rat
      model of CRF under conditions of normal and restricted dietary phosphate intake.
      In this model of renal disease, we found that there is no significant change in
      the phosphate absorption in either the duodenum or jejunum regardless of the
      dietary phosphate intake. There was also no change in the expression of the
      messenger RNA of the major intestinal phosphate carrier the sodium-dependent-IIb
      transporter. Furthermore, we found no change in the intestinal villus length or
      in the location of phosphate uptake along the villus. Our results indicate that
      in CRF, unlike the kidney, there is no reduction in phosphate transport across
      the small intestine. This makes intestinal phosphate absorption a potential
      target in the prevention and treatment of hyperphosphatemia.

PMID- 17457377
TI  - Podocytes in culture: past, present, and future.
AB  - Human genetic and in vivo animal studies have helped to define the critical
      importance of podocytes for kidney function in health and disease. However, as in
      any other research area, by default these approaches do not allow for mechanistic
      studies. Such mechanistic studies require the availability of cells grown ex vivo
      (i.e., in culture) with the ability to directly study mechanistic events and
      control the environment such that specific hypotheses can be tested. A seminal
      breakthrough came about a decade ago with the documentation of differentiation in
      culture of primary rat and human podocytes and the subsequent development of
      conditionally immortalized differentiated podocyte cell lines that allow
      deciphering the decisive steps of differentiation and function of 'in vivo'
      podocytes. Although this paper is not intended to provide a comprehensive review
      of podocyte biology, nor their role in proteinuric renal diseases or progressive
      glomerulosclerosis, it will focus specifically on several aspects of podocytes in
      culture. In particular, we will discuss the scientific and research rationale and
      need for cultured podocytes, how podocyte cell-culture evolved, and how cultured
      podocytes are currently being used to uncover novel functions of podocytes that
      can then be validated in vivo in animal or human studies. In addition, we provide
      a detailed description of how to properly culture and characterize podocytes to
      avoid potential pitfalls.

PMID- 17457378
TI  - PPAR-gamma agonist protects podocytes from injury.
AB  - Podocyte injury and loss contribute to progressive glomerulosclerosis. Peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear hormone receptor,
      which we have found to be increased in podocytes in a variety of kidney diseases.
      It is not known if PPAR-gamma contributes to renal injury or if it serves as a
      countermeasure to limit renal injury during disease progression. We tested these
      possibilities utilizing the puromycin aminonucleoside (PAN) model of renal injury
      in immortalized mouse podocytes. The cultured podocytes expressed PPAR-gamma mRNA
      at baseline but this was decreased by PAN. Pioglitazone, a pharmacologic agonist
      of PPAR-gamma, increased both PPAR-gamma mRNA and activity in injured podocytes,
      as assessed by a reporter plasmid assay. Further, pioglitazone significantly
      decreased PAN-induced podocyte apoptosis and necrosis while restoring podocyte
      differentiation. The PPAR-gamma agonist significantly restored expression of the
      cyclin-dependent kinase inhibitor p27 and the antiapoptotic molecule Bcl-xL while
      significantly decreasing proapoptotic caspase-3 activity. Pioglitazone tended to
      decrease PAN-induced transforming growth factor-beta (TGF-beta) mRNA expression.
      Our study shows that PPAR-gamma is normally expressed by podocytes and its
      activation is protective against PAN-induced apoptosis and necrosis. We postulate
      that this protective effect may be mediated in part by effects on p27 and TGF
      beta expression.

PMID- 17457379
TI  - Cardiac remodeling and dysfunction in nephrotic syndrome.
AB  - There is an increased incidence of heart disease in patients with chronic
      nephrotic syndrome (NS), which may be attributable to the malnutrition and
      activated inflammatory state accompanying the sustained proteinuria. In this
      study, we evaluated renal function, cardiac morphometry, contractile function,
      and myocardial gene expression in the established puromycin aminonucleoside
      nephrosis rat model of NS. Two weeks after aminonucleoside injection, there was
      massive proteinuria, decreased creatinine clearance, and a negative sodium
      balance. Skeletal and cardiac muscle atrophy was present and was accompanied by
      impaired left ventricular (LV) hemodynamic function along with decreased
      contractile properties of isolated LV muscle strips. The expression of selected
      cytokines and proteins involved in calcium handling in myocardial tissue was
      evaluated by real time polymerase chain reaction. This revealed that the
      expression of interleukin-1beta, tumor necrosis factor-alpha, and phospholamban
      were elevated, whereas that of cardiac sarco(endo)plasmic reticulum calcium pump
      protein was decreased. We suggest that protein wasting and systemic inflammatory
      activation during NS contribute to cardiac remodeling and dysfunction.

PMID- 17457380
TI  - Gender-specific association of adiponectin as a predictor of progression of
      chronic kidney disease: the Mild to Moderate Kidney Disease Study.
AB  - Progressive renal vascular sclerosis is a key feature of chronic kidney disease
      (CKD). Adiponectin, an adipokine with potent anti-inflammatory and
      antiatherosclerotic properties, is associated with insulin resistance, type II
      diabetes and cardiovascular disease. In this study, we evaluated the predictive
      value of adiponectin for the progression of CKD in patients enrolled in the Mild
      to Moderate Kidney Disease Study. The primary end point was defined as a doubling
      of the baseline serum creatinine and/or terminal renal failure in 177 patients
      who completed a prospective follow-up of 7 years. Patients who reached a
      progression endpoint (n=65) were significantly older, had higher baseline serum
      creatinine, proteinuria and adiponectin concentrations and more components of the
      metabolic syndrome. A gender-stratified Cox model revealed adiponectin in men as
      a significant predictor of progression after adjustment for age, glomerular
      filtration rate, and proteinuria. Male patients with adiponectin levels above
      their ROC analysis-derived optimal cutoff of 4 microg/ml had a significantly
      faster progression than patients below this point. This prospective long-term
      study in patients with CKD indicates high adiponectin as a novel independent
      predictor of disease progression in men but not in women. Our observation may be
      relevant for other conditions of progressive vascular sclerosis and diabetic
      nephropathy.

PMID- 17457381
TI  - [Research procurement as a priority].

PMID- 17457382
TI  - [Spontaneous cerebral hemorrhage--how much treatment?].

PMID- 17457383
TI  - [Smaller, but heavier hand baggage].

PMID- 17457384
TI  - [Acute poisoning and statistics].

PMID- 17457385
TI  - [Acute poisonings in Norway 1999-2004--morbidity and mortality].
AB  - BACKGROUND: Monitoring of acute poisoning is important for health authorities.
      There have been local studies and national studies in limited areas such as drug
      poisoning, but morbidity and mortality associated with acute poisoning has not
      been presented collectively at a national level. The aim of the study is to
      establish morbidity and mortality associated with acute poisoning in Norway.
      MATERIAL AND METHODS: The study material comprised data from the Norwegian
      Patient Register and the Norwegian Causes of Death Register on patients with
      acute poisoning from 1999 through 2004. Data from somatic hospitals include
      patients who were discharged after 5 hours. RESULTS: Almost 11,000 discharges
      with acute poisoning, coded as main or other condition (ICD-10 F and T codes),
      were recorded from somatic hospitals annually. The hospital mortality was 0.8 %.
      About 500 acute poisoning deaths occurred annually, 20 % within and 80 % of them
      outside hospitals. INTERPRETATION: The results show increased morbidity and
      stable mortality by acute poisoning in Norway, 1999-2004. Information in the
      Cause-of-Death and especially the Patient Register should be improved. More
      detailed information by type of drugs and substances and external causes are
      needed for monitoring and prevention.

PMID- 17457386
TI  - [Psychotropic medicines to patients with mental retardation].
AB  - BACKGROUND: Psychotropic drugs are widely used by mentally retarded persons. Our
      aim was to describe changes in prescription practice and use of such drugs after
      patients were moved from institutions to community care. METHOD: 101 individuals
      with mental retardation, previously living in institutions, were included in our
      study. Their caregivers were requested to answer a questionnaire. RESULTS: 44% of
      the study population were taking psychotropic medication; the most commonly used
      were antipsychotic drugs. Psychiatric disorders and behaviour problems were the
      most common reasons for prescriptions. The effects and side effects were in most
      cases not recorded. Other types of treatment, such as analysis and adaptation of
      environmental factors, were seldom used. Specialists in habilitation and
      psychiatry were rarely involved in the treatment. INTERPRETATION: Many
      individuals with mental retardation use psychotropic drugs. The survey indicates
      an increased use of these drugs after patients moving from institutions to
      community care. It also seems that treatment given at the institution was
      continued. Psychotropic drug treatment is complicated and should be handled by
      specialists in psychiatry or habilitation.

PMID- 17457387
TI  - [Endoscopic treatment of vesicoureteral reflux in children].
AB  - BACKGROUND: At Rikshospitalet, Norway, vesicoureteral reflux (VUR) in children
      has been treated with subureteric teflon (polytetrafluoroethylen) injection
      (STING) since 1994. After a biological injection substance became commercially
      available, we changed to Deflux (dextranomer/hyaluronic acid) in 2000. The aim of
      this study was to assess whether the VUR results following use of the new
      injection substance are comparable to those for the previously used substance.
      MATERIAL AND METHODS: 202 ureters with VUR grade II-V in 132 patients (91 girls)
      were treated for the first time with subureteric injections of teflon (n = 77) or
      Deflux (n = 125) during the 5-year period November 1998-2003. The charts were
      retrospectively reviewed. RESULTS: 201 ureters (131 patients) were followed up
      with urinary tract ultrasound and voiding cystogram 1-34 months after the last
      injection. After the first teflon injection 43% of the ureters had no reflux and
      an additional 9% were improved. After the first Deflux injection 48 % of the
      ureters had no reflux and 10% were improved. After 1-3 injections 78% (teflon
      71%, Deflux 81%) were without or had reduced VUR. Three ureters showed terminal
      stenosis after the first Deflux injection. Statistically, the results were
      independent of VUR grade, injection substance and surgeon experience, and similar
      for duplex and single ureters. INTERPRETATION: Endoscopic treatment of VUR in
      children is safe and simple. The results after Deflux and teflon were similar.
      Urinary tract ultrasound and voiding cystogram should be used for follow-up of
      all patients some months after injection.

PMID- 17457388
TI  - [Allergy vaccination in Norway].
AB  - BACKGROUND: Allergen-specific immunotherapy is an important treatment option for
      severe allergy to air-borne allergens and insects, but is less used in Norway
      than in other Scandinavian countries. MATERIAL AND METHODS: A questionnaire was
      sent to hospitals and private centres that offered immunotherapy in 2005. The
      number of patients treated, treatment regimes, the allergens used for
      immunotherapy and the occurrence of systemic side effects during treatment were
      recorded. RESULTS: 2,400 patients (5.2 per 10,000 inhabitants) received
      immunotherapy in 2005. The numbers of patients treated, types of regimes and
      allergens used for immunotherapy varied significantly between counties. The
      number of patients receiving immunotherapy was significantly lower than in our
      neighbouring countries. The number of systemic side effects was low. Severe, but
      not life-threatening events occurred in 1.2 of 1,000 injections; no anaphylactic
      reaction was reported. INTERPRETATION: The availability of allergen-specific
      immunotherapy varies substantially in Norway.

PMID- 17457389
TI  - [Anticancer drug dosing--pharmacogenomic biomarkers or body surface area?].
AB  - BACKGROUND: Chemotherapeutic treatment regimes are established for most cancer
      forms. In general, these substances have extremely narrow therapeutic windows,
      which render cancer patients vulnerable to over- and underdosing. Individual drug
      dosing is currently based on the patients' body surface area. This practice is an
      extrapolation from animal studies. Recent advances in molecular medicine raise
      the question of whether the present dosing strategy should be adjusted to
      individual functional DNA variants affecting the metabolism, transport and
      efficacy of anticancer drugs. MATERIAL AND METHODS: This review is based on
      selected references retrieved from PubMed and the authors' experience in drug
      treatment of cancer patients. RESULTS: Several single nucleotide polymorphisms
      and other DNA variants that contribute to varying clinical response to
      chemotherapeutic agents were identified. For some drugs it has been shown that
      unfavourable DNA variants can lead to life-threatening side effects and/or
      suboptimal treatment. INTERPRETATION: There is a compelling need for prospective,
      randomized studies to establish the prognostic values of pharmacogenomic markers.
      With few exceptions the current knowledge is insufficient to include genotype
      analyses in routine planning of anticancer drug treatment. In most clinical
      situations, individual drug dosing according to body surface area in addition to
      therapeutic drug monitoring and close clinical surveillance is still the
      preferred approach to treat cancer patients.

PMID- 17457390
TI  - [Cryopreservation of ovarian tissue].
AB  - BACKGROUND: Unfertilized oocytes, embryos and ovarian issue can be cryopreserved
      before cancer treatment of post-pubertal women. Fertility may be restored by
      retransplantation in women who are pronounced healthy. MATERIAL AND METHODS: The
      article is based on relevant literature and our own clinical experience since
      2004, when the procedure was first allowed in Norway. RESULTS AND INTERPRETATION:
      Cryopreservation of ovarian tissue is an established procedure in Norway. As of
      January 2007, ovarian tissue from 22 women, aged 14-35 years, has been
      cryopreserved at Rikshospitalet. There is an upper age limit of 35 years because
      of age-related follicular loss. The treating oncologist and a gynaecologist
      should be responsible for informing patients about the possibility of preserving
      fertility by ovarian cryopreservation before chemo- and/or radiation therapy. The
      patient should, at the same time, be told about the limited world-wide experience
      with this procedure.

PMID- 17457391
TI  - [The good discharge summary--criteria and evaluation].
AB  - BACKGROUND: A discharge summary should be sent to the primary care physicians to
      ensure adequate follow-up of patients after discharge from hospital. It should
      arrive in due time and its content should serve its purpose. MATERIAL AND
      METHODS: We identified six criteria to be used for quality evaluation of
      discharge summary content and format. Two general practitioners and two hospital
      physicians applied the criteria in an evaluation of 50 consecutive discharge
      summaries from a department of internal medicine. The six criteria were given a
      score from 1 to 4 for each discharge summary. RESULTS AND INTERPRETATION: The
      scores showed only a modest inter-rater agreement between the four evaluators.
      The hospital physicians tended to give higher scores than primary care
      physicians. The inter-rater agreement was best for information about medicines
      (mean weighted kappa 0.17) and ortograhy (mean weighted kappa 0.13).
      Collectively, the evaluators judged the discharge summaries to be of overall fair
      to good quality, although 44% of the summaries were given a poor score for at
      least one criterion. We suggest ways to ensure high quality content in discharge
      summaries.

PMID- 17457392
TI  - [Lower digitalis dosage in heart failure].

PMID- 17457393
TI  - [Treatment of acute ischemic stroke].
AB  - BACKGROUND: Treatment of acute ischemic stroke changes rapidly. The purpose of
      this article is to present current therapeutic options. MATERIAL AND METHODS: The
      review is based on relevant literature found through a Medline search and on
      personal clinical experience. RESULTS: Acute treatment of ischemic stroke
      encompasses specific therapy aimed at recanalising the occluded vessel (chemical
      or mechanical thrombolysis) and treatment aimed at protection from the cellular
      consequences of ischemia (neuroprotection). Acute treatment also encompasses
      general stabilisation of a critically ill patient; with focus on blood pressure,
      cardiovascular function, airways, breathing and metabolic disturbances such as
      hyperglycemia and hyperthermia. Time is a crucial single factor for treatment
      effect. A rapid chain of delivery and a well-functioning stroke unit are
      therefore necessary prerequisites for effective acute stroke treatment.
      INTERPRETATION: Effective treatment of acute ischemic stroke is available and
      should whenever possible be evidence-based. Treatment based on experience and
      pathophysiological reasoning should be used when scientific evidence lacks.

PMID- 17457394
TI  - [Spontaneous intracerebral hemorrhage].
AB  - BACKGROUND: Cerebral stroke caused by intracerebral hemorrhage is serious. This
      review presents updated knowledge about the condition. MATERIAL AND METHODS: The
      review is based on pivotal articles published during recent years, identified
      through a PubMed search applying the key words "intracerebral haemorrhage", and
      our own clinical experience. RESULTS AND INTERPRETATION: Intracerebral hemorrhage
      strikes about 1,000 persons in Norway annually. Hypertension is the single most
      important risk factor. Cerebral CT confirms the diagnosis. Almost half of the
      patients die during the first month after the hemorrhage, many during the first
      two days. About 20% of the patients can manage without help after the first six
      months. Treatment includes measures against increased intracranial pressure and
      in selected cases surgical evacuation of the haematoma, especially in cases of
      bleeding into the cerebellum. Recombinant factor VIIa infused within the first
      three hours to stop the bleeding can play an important role in the acute phase.
      Patients below the age of 45, patients without hypertension, and patients with
      lobar haemorrhage and signs of clinical deterioration should be thoroughly
      investigated to disclose a potential arteriovenous malformation or an aneurysm.
      Neurointensive care may give better clinical results and the condition should
      ideally be treated in an intensive care unit.

PMID- 17457395
TI  - [Cerebral venous thrombosis--diagnosis and treatment].
AB  - BACKGROUND: Cerebral venous thrombosis (CVT) is a rare cause of stroke, and an
      important differential diagnosis for a number of neurological complaints. This
      review article concerns the aetiology, pathology, diagnostic work-up and
      treatment of the condition. MATERIAL AND METHODS: This article is based on a
      review of relevant literature and on the authors' personal experience. RESULTS
      AND INTERPRETATION: CVT is thought to be responsible for about 0.5-1.0% of all
      strokes. Headache is the initial symptom in 70-90% of the cases. Apart from this,
      symptoms vary considerably. CVT was previously assumed to be a rare condition
      with a high mortality, as the diagnosis could in effect only be made post mortem.
      Conditions with a benign course can now be diagnosed with modern
      neuroradiological examinations. All patients should be assessed carefully;
      particular attention should be given to possible congenital or acquired forms of
      thrombophilia. Scepsis about the use of anticoagulants in CVT has long prevailed,
      especially in connection with haemorrhagic infarcts. During the last 10-15 years,
      several studies indicate that anticoagulation with heparin, or low-molecular
      heparin, should be the initial treatment of choice. Catheter-based endovascular
      thrombolytic treatment should be considered in serious cases where anticoagulant
      treatment is unsuccessful. Mortality is about 10%.

PMID- 17457396
TI  - [Subarachnoid haemorrhage--diagnosis and management].
AB  - INTRODUCTION: Subarachnoid haemorrhage (SAH) causes 3% of all strokes and is
      caused by a ruptured cerebral aneurysm in four of five cases. This review article
      presents an update of knowledge on symptoms, diagnosis and management of SAH.
      MATERIAL AND METHODS: This article is based on selected literature and the
      authors' clinical experience. RESULTS AND INTERPRETATION: The mortality of SAH is
      approximately 50% and one out of three survivors have permanent disabling
      neurological symptoms. Patients with suspected or diagnosed SAH need urgent
      examination and treatment. A large randomised multicentre study (International
      Subarachnoid Aneurysm Trial) suggests that endovascular repair with coiling may
      be less traumatic than microsurgery. Not all patients are suitable for
      endovascular treatment, despite new tools like balloon- and stent-assisted
      coiling. Centres that treat patients with SAH should have both methods available
      at all hours. The management of these patients involves advanced neuro-intensive
      care, and co-operation between neurosurgeons, neuroradiologists and
      neuroanestesiologists.

PMID- 17457397
TI  - [Communication and leadership in health care].

PMID- 17457398
TI  - [Wrong about cord blood tests].

PMID- 17457399
TI  - [The Norwegian Thyroid Society wishes better cooperation with physicians].

PMID- 17457402
TI  - [What can physicians do against climate changes].

PMID- 17457406
TI  - [Maternal mortality still high].

PMID- 17457409
TI  - Creation of quaternary stereocenters in carbonyl allylation reactions.
AB  - Despite the advances in stereoselective carbonyl allylation reactions, the
      creation of quaternary stereocenters in the addition of 3,3'-disubstituted
      allylmetals to aldehydes is still a challenging issue. This feature article
      describes the most powerful approaches that have been devised to address this
      problem.

PMID- 17457410
TI  - Increased single nucleotide discrimination in arrayed primer elongation by 4'C
      modified primer probes.
AB  - Herein we describe the beneficial impact of immobilized 4'C-modified primer
      probes on detecting single nucleotide variations in arrayed primer extension by a
      DNA polymerase.

PMID- 17457411
TI  - A novel Ir-hexaaluminate catalyst for N(2)O as a propellant.
AB  - Aiming for designing a novel catalyst for N(2)O as a green propellant, Ir
      substituted hexaaluminate, which can initiate N(2)O decomposition at 623 K and
      can sustain the stability at 1473 K, has been developed for the first time.

PMID- 17457412
TI  - Acid-induced photochromic system switching of diarylethene derivatives between P-
      and T-types.
AB  - P-type photochromic diarylethenes having a diethylamino group can switch to T
      type photochromic system by the addition of trifluoromethanesulfonic acid as
      external stimuli.

PMID- 17457413
TI  - Active site mutagenesis of the putative Diels-Alderase macrophomate synthase.
AB  - Although the macrophomate synthase active site is rich in potential functional
      groups, site-directed mutagenesis shows that only three residues are absolutely
      required for catalysis of oxaloacetate decarboxylation and trapping of the
      resulting enolate with a 2-pyrone; the other residues that line the binding
      pocket are surprisingly tolerant to substitution.

PMID- 17457414
TI  - Conjugated alternating copolymers containing both donor and acceptor moieties in
      the main chain.
AB  - A straightforward synthesis toward two conjugated alternating copolymers
      consisting of 2,7-linked carbazole donor (2,7-Cz) and ladderized pentaphenylene
      with diketone bridge (LPPK) acceptor chromophores is reported: the copolymers
      differ by the repeat unit ratio between the 2,7-Cz and LPPK units within the
      backbone; energy and charge transfer properties and supramolecular organizations
      of donor-acceptor moieties in these copolymers have been studied via optical
      spectroscopy and two-dimensional wide-angle X-ray scattering (2D-WAXS);
      preliminary results such as the efficient energy and charge transfer and pi
      stacking character in the solid state suggest that the copolymers are potentially
      useful for photovoltaic devices.

PMID- 17457415
TI  - An unprecedented twofold interpenetrating (3,4)-connected 3-D metal-organic
      framework.
AB  - An unprecedented twofold interpenetrating (3,4)-connected topology of the
      Cu(3)L(4)-type metal-organic framework was prepared using N,N',N''-tris(4
      pyridinyl)-1,3,5-benzenetricarboxamide (L) as a trigonal three-connection node
      and the copper(ii) ion as a square planar four-connection node, where the
      framework contains remarkably large 1-D solvent channels.

PMID- 17457416
TI  - A stable electrode for high-potential, electrocatalytic O(2) reduction based on
      rational attachment of a blue copper oxidase to a graphite surface.
AB  - Attachment of substrate-like anthracene based units to the surface of pyrolytic
      graphite greatly enhances the adsorption of high-potential fungal laccases,
      'blue' Cu enzymes that catalyse the four-electron reduction of O(2), providing a
      stable cathode for enzymatic biological fuel cells and electrochemical studies.

PMID- 17457417
TI  - Genotoxicity screening for N-nitroso compounds. Electrochemical and
      electrochemiluminescent detection of human enzyme-generated DNA damage from N
      nitrosopyrrolidine.
AB  - We report for the first time voltammetric/electrochemiluminescent sensors applied
      to predict genotoxicity of N-nitroso compounds bioactivated by human cytochrome
      P450 enzymes.

PMID- 17457418
TI  - Luminescent lanthanide bimetallic triple-stranded helicates as potential cellular
      imaging probes.
AB  - Water-soluble triple-stranded [Ln(2)(L)(3)] helicates have been successfully
      tested as imaging probes in human cervical adenocarcinoma cells (HeLa), the
      complex being not toxic and clearly staining their cytoplasm in a concentration
      dependent manner.

PMID- 17457419
TI  - Platination of superoxide dismutase with cisplatin: tracking the ammonia ligands
      using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS).
AB  - The high mass accuracy of FT-ICR MS combined with (15)N-labelling shows that mono
      and di- platinated products from the reaction of erythrocyte superoxide
      dismutase with the anticancer drug cisplatin in solution retain their ammine
      ligands, in contrast to a recent X-ray crystallographic study.

PMID- 17457420
TI  - Bioconjugation onto biological surfaces with fluorescently labeled polymers.
AB  - Direct bioconjugation onto hair fibers, monitored by confocal laser scanning
      microscopy and differential scanning calorimetry, has been performed using NHS
      alpha-functional fluorescently tagged polymers synthesised by living radical
      polymerisation.

PMID- 17457421
TI  - Reducing charge recombination losses in solid state dye sensitized solar cells:
      the use of donor-acceptor sensitizer dyes.
AB  - Herein we report the application of supramolecular dyes to control charge
      recombination between photo-injected electrons and oxidized hole-transporting
      material, resulting in an enhancement in the performance of dye sensitized solar
      cell devices based upon such dyes.

PMID- 17457422
TI  - Synthesis and structural characterization of a molecular plutonium(IV) compound
      constructed from dimeric building blocks.
AB  - Single crystals of Na(8)Pu(2)(O(2))(2)(CO(3))(6) x 12H(2)O, exhibiting bridging
      mu(2),eta(2)-O(2) ligands in unprecedented Pu(IV) dimeric units, were obtained at
      ambient temperature from an aqueous Pu(IV) peroxide carbonate solution.

PMID- 17457423
TI  - Photocrosslinked nitroxide polymer cathode-active materials for application in an
      organic-based paper battery.
AB  - A nitroxide radical functional polymer was photocrosslinked for the first time
      without significant side reactions, producing a cathode-active thin film, leading
      to an organic-based paper battery.

PMID- 17457424
TI  - Electrochemical synthesis of metal and semimetal nanotube-nanowire
      heterojunctions and their electronic transport properties.
AB  - Metal and semimetal nanotube-nanowire heterojunction arrays have been achieved by
      sequential electrochemical-deposition inside the nanochannels of anodic aluminium
      oxide template with a layer of Au thin enough to leave the pores open.

PMID- 17457425
TI  - Conformational control of HCl co-transporter: imidazole functionalised
      isophthalamide vs. 2,6-dicarboxamidopyridine.
AB  - Replacement of the central isophthalamide core in a synthetic HCl receptor, with
      a 2,6-dicarboxamidopyridine, leads to a more preorganised molecular structure
      that exhibits higher chloride affinity and membrane transport flux.

PMID- 17457426
TI  - Catalytic asymmetric hydrogenation of aldehydes.
AB  - Racemic alpha-arylaldehydes provide the corresponding primary alcohols via
      dynamic kinetic resolution in excellent enantioselectivities and yields upon
      hydrogenation using a Noyori ruthenium catalyst; for example, the biologically
      active (S)-enantiomer of the non-steroidal anti-inflammatory drug ibuprofen could
      be synthesized via catalytic enantioselective hydrogenation of aldehyde followed
      by oxidation with potassium permanganate in 76% isolated yield and 96 : 4 er.

PMID- 17457427
TI  - Aryl bromide/triflate selectivities reveal mechanistic divergence in palladium
      catalysed couplings; the Suzuki-Miyaura anomaly.
AB  - In palladium-catalysed cross-coupling reactions, the outcome of competition
      between aryl bromides and aryl triflates depends on the nucleophilic partner;
      Suzuki couplings with R-B generally follow a different pattern from other R-M
      species.

PMID- 17457428
TI  - The isolation and photochemistry of individual atropisomers of photochromic
      diarylethenes.
AB  - All three atropisomers of photochromic diarylethenes were isolated for the first
      time and the stereospecific photochemical switching process studied by UV-vis and
      CD spectroscopy.

PMID- 17457429
TI  - Trimorphism in solid resorcinarenes.
AB  - Nonylresorcinarene, in contrast to methylresorcinarene and nonylpyrogallene,
      exists in three isolable phases: a layer structure, a hexamer and an amorphous
      phase; the three are in thermal equilibrium.

PMID- 17457430
TI  - The outside knows the difference inside: trapping helium by immediate reduction
      of the orifice size of an open-cage fullerene and the effect of encapsulated
      helium and hydrogen upon the NMR of a proton directly attached to the outside.
AB  - A methodology to entrap He inside an open-cage fullerene by immediate reduction
      of the size of an orifice was developed, and the effects of encapsulated He and
      H(2) on the chemical shift of a proton directly attached to the outer fullerene
      sphere were revealed.

PMID- 17457431
TI  - The cost of new therapies in cardiovascular care. Time for hope or despair for
      developing countries.
AB  - In recent years, remarkable therapeutic advances have been made in the field of
      interventional cardiology with the introduction of statins, thienopyridines, such
      as clopidogrel and drug-eluting stents. Only a small minority in developing
      countries can afford these new treatment modalities, while the public health
      system would be rapidly bankrupted if it were to provide these modalities for all
      patients who might benefit from it. The purpose of this review article is to
      provide insight regarding the cost-effectiveness of these new treatment
      strategies and to address the added costs resulting upon their adoption and their
      appropriateness in developing countries.

PMID- 17457432
TI  - Expression of p21 and p27 in gallbladder cancer.
AB  - OBJECTIVE: To investigate the expression of p21 and p27 factors in gallbladder
      cancer (GBC), and to correlate their expression with clinicopathological
      parameters: age, gender, stage, invasion, and grade. METHODS: Thirty-two
      surgically resected specimens were collected between 1994-2001 from different
      health centers in north Jordan. Tissues belong to 25 females and 7 males were
      examined immunohistochemically. The study took place in the Pathology Department,
      Jordan University of Science and Technology, Jordan. RESULTS: Levels of p21 were
      found in 75% and p27 in 25%. Furthermore, p21 was expressed in 50% of the
      specimens which are belong to patients with ages <64 years, whereas all specimens
      for ages >64 years have p21WAF1/CIP1 expression (p=0.001). The expression of p21
      between advanced stages (stages III and IV) was 89.5% and early stages (stages I
      and II) was 53.8 % (p=0.031). CONCLUSION: The p27 expression was markedly
      decreased in GBC cases (25%) and there were no significant correlation between
      p27KIP1 expression and all clinicopathological parameters including gender, World
      Health Organization grades, stages, and invasion, whereas the expression of p21
      was 75% and there was a significant correlation between p21 and the
      clinicopathological parameters including gender, stages, and invasion.

PMID- 17457433
TI  - The role of hepatocyte growth factor in the differentiation of dendritic cells
      from peripheral blood monocytes.
AB  - OBJECTIVE: To find out the effects of hepatocyte growth factor (HGF) in the
      development of dendritic cells (DC) from the peripheral monocytes. METHODS: The
      study was carried out in Black Sea Technical University Hospital, Trabzon, Turkey
      between 2003-2004. Seven different cytokine combinations were employed to assess
      phenotypical and functional differences of DCs from the peripheral monocytes in
      serum free culture media. Peripheral monocytes were incubated in media with
      cytokines for 5 days. The tumor necrosis factor-alpha (TNF-alpha) was added to
      the cell culture on day 5 and incubated for another 2 days. Surface and co
      stimulating molecules on the cells were assessed by flowcytometry. The functional
      capacity of the DCs was evaluated on day 7 by purified protein derivative loading
      and subsequent lymphoproliferation test using methyl tetrazolium staining.
      RESULTS: On the 5th day of incubation DC development was observed in all cytokine
      groups, but cells were superior in cultures maintained in the presence of
      interleukin-4 combinations with granulocyte-macrophage colony stimulating factor
      (GM-CSF) or with GM-CSF+HGF. Moreover, the expression of surface and co
      stimulating molecules increased significantly after incubation with TNF-alpha.
      The effect of PPD loaded-DCs on proliferation of lymphocytes was more striking in
      HGF containing groups. CONCLUSION: It was concluded that HGF supplemented
      cultures exert some additive effects in relation to function of monocyte-derived
      DCs. But HGF alone does not seem to augment monocyte-derived DC proliferation and
      maturation significantly.

PMID- 17457434
TI  - Homeostasis status between prooxidants and antioxidants as a potent marker in
      Iranian preeclamptic patients.
AB  - OBJECTIVE: To measure the plasma oxidant, lipid peroxidation and antioxidants,
      ascorbate, to magnify the prooxidants and antioxidants status as a marker of pre
      eclampsia. METHODS: Included in the study were 50 preeclamptic and 100
      normotensive pregnant women of singleton gestations in their third trimester,
      presented in Allavi Hospitals in Ardabil province of Iran from August 2004 to
      April 2005. Among these patients plasma malonaldehyde (MDA) and vitamin C
      concentration were analyzed. Blood samples (5 ml) were collected aseptically in
      heparin bulb. Spectrophotometric methods were employed to determine the plasma
      concentrations of vitamin C. The Statistical Package for Social Sciences software
      was used to analyze the data. RESULTS: In preeclampsia, significant increase in
      prooxidant MDA was observed as compared to controls. A significant fall in
      antioxidants vitamin C was noted in preeclampsia as compared to control. The MDA
      showed a significant balance to the level of vitamin C. CONCLUSION:
      Administration of regular nutritive supplementation containing reducing systems
      like vitamin C should help in maintaining the equilibrium during normal pregnancy
      and theoretically in preeclampsia too but to what extent they help in clinical
      practice is still being investigated.

PMID- 17457435
TI  - The role of adenosine triphosphate-regulated potassium channels in propofol
      induced beneficial effect on contractile function of hypercholesterolemic
      isolated rabbit hearts.
AB  - OBJECTIVE: To investigate the role of adenosine triphosphate-regulated potassium
      (KATP) channels in the propofol-induced changes in the contractile function of
      hypercholesterolemic rabbit hearts. METHODS: This study was carried out in the
      Department of Pharmacology Laboratory, Faculty of Medicine, Dokuz Eylul
      University, Izmir, Turkey during the period January to December 2003. Twenty-two
      isolated rabbit hearts were grouped into 4. Group I (n=6) were infused with 50
      microM propofol during a 60 minutes perfusion. Group II (n=6) were also infused
      with 100 microM propofol over the same period. Group III (n=5) was perfused with
      solutions containing 10 microM glybenclamide and group IV (n=5) 100 microM
      diazoxide for 5 minutes before and during a 60 minutes infusion with 100 microM
      propofol. RESULTS: The 50 microM propofol infusion decreased left ventricular
      pressure (LVP) significantly (p<0.05) but it did not change dP/dt max and dP/dt
      min. The 100 microM propofol infusion caused a significant increase in LVP at 20
      minutes. Furthermore, a 100 microM propofol infusion resulted in a significant
      increase in maximal positive left ventricular pressure (dP/dt max) and maximal
      negative left ventricular pressure (dP/dt min) compared to baseline (p<0.05). The
      increase in dP/dtmax and dP/dt min induced by 100 microM propofol was inhibited
      by glybenclamide (p<0.05), a KATP channel blocker, but was not affected by
      diazoxide (p>0.05), a KATP channel opener. CONCLUSION: The activation of KATP
      channels seems to be one of the mechanisms by which propofol induced beneficial
      effect on contractility of myocardium in hypercholesterolemic rabbit hearts.

PMID- 17457436
TI  - Comparison between intraarticular triamcinolone acetonide and methylprednisolone
      acetate injections in treatment of frozen shoulder.
AB  - OBJECTIVE: To compare the effectiveness of triamcinolone acetonide (40 mg) and
      methylprednisolone acetate (60 mg) in Iraqi patients with primary and secondary
      frozen shoulder. METHODS: A total number of 135 (93 males and 42 females)
      patients with frozen shoulder, allocated at outpatient clinic of rheumatology in
      Al-Yarmook Teaching Hospital (Baghdad-Iraq) from January 2004 to December 2005,
      were enrolled in non-controlled clinical trial. The diagnosis of frozen shoulder
      was made using the guidelines for shoulder complaint issued by the Dutch College
      of General Practitioners. Intraarticular injections of 40 mg triamcinolone
      acetonide (46 males and 22 females) or 60 mg methylprednisolone acetate (47 males
      and 20 females) were given every 3 weeks (not more than 3 injections) by using
      posterior route. RESULTS: Both triamcinolone acetonide (81.8%) and
      methylprednisolone acetate (83.3%) were equally effective in primary frozen
      shoulder. Triamcinolone acetonide is significantly improved diabetic frozen
      shoulder in comparison to methylprednisolone acetate (69% versus 39%). Also
      patients on triamcinolone acetonide required less number of steroid injections
      and higher percent of severe cases were significantly improved by triamcinolone
      acetonide in comparison with methylprednisolone acetate. CONCLUSION: We conclude
      that triamcinolone acetonide is a good rescue for painful stiff shoulder
      particularly for resistant cases as with diabetes mellitus, and with long
      duration of illness. Also, its efficacy can be observed with less frequent
      injections.

PMID- 17457437
TI  - Effects of intraarticular contrast media on synovial membrane and cartilage. An
      electron microscopic evaluation in rabbit knees.
AB  - OBJECTIVE: To evaluate the histological and ultrastructural alterations in rabbit
      knee joint cartilage and synovia induced by intraarticular injections of 2 water
      soluble contrast agents. METHODS: The study was conducted at the Department of
      Orthopedics and Traumatology, Medical Faculty, Osmangazi University, Eskisehir,
      Turkey in January 2002. To examine the effect of contrast agents on articular
      cartilage and synovial membrane, rabbit model was used. Specimens from 62 knee
      joints were examined by light microscopy and transmission electron microscopy one
      hour, one day, one week and 2 weeks after intraarticular administration of
      gadolinium-diethylenetriamine pentaacetic acid, iopromide or saline. RESULTS: In
      the knees injected with saline, light microscopic changes of the synovium
      consisted of edema only. Edema and hyperemia were seen in contrast agent injected
      knees. Ultrastructurally, numerous and large pinocytotic vesicles in A cells of
      the synovial membrane were seen in contrast agent injected groups. In the knees
      injected with saline the cartilage were ultrastructurally normal but contrast
      agent injected knees showed increased activation of chondrocytes with increase of
      dense glycogen accumulation, large lipid vacuoles and matrix material. There were
      very rare pycnotic cells in these samples. The rating scale has been used and the
      means of the total scores were determined for the groups. CONCLUSION: The effects
      of contrast agents reduced gradually on the cartilage and synovium in general but
      did not become completely normal in the observation period.

PMID- 17457438
TI  - Increased serum anti-mycobacterial antibody titers in rheumatoid arthritis
      patients. Is there any specific antigenic target?
AB  - OBJECTIVE: To investigate the presence of immunoreactivity against mycobacterial
      antigens in the sera of patients with rheumatoid arthritis (RA) and to detect the
      target of the immune reaction. METHODS: This study was carried out on 60 patients
      with RA, and 25 patients with no joint diseases in the laboratory of Clinical
      Microbiology Department of Ankara University Medical Faculty, Ankara, Turkey
      between July 2003 to January 2004. Secreted and cellular antigens of
      Mycobacterium tuberculosis (M. tuberculosis) H37Rv and Mycobacterium bovis (M.
      bovis) were isolated and purified by high performance liquid chromatography to
      antigenic fractions. The immunoreactivity of patient and control sera against
      these antigens were determined by enzyme-linked immunosorbent assay (ELISA).
      RESULTS: Immunoreactivity against mycobacterial antigens in RA patients were
      significantly higher than controls. Significant difference between patients and
      controls has been determined with M. bovis Bacillus Calmette Guerin (BCG) culture
      fluid and sonicate antigens, but not with M. tuberculosis H37Rv. This suggests
      that the antigen triggering immune response in patients with RA may belong to or
      mainly expressed on M. bovis BCG. The ELISA results showed significant difference
      between RA patients and controls with all antigenic fractions. CONCLUSION:
      Presence of increased immunoreactivity against mycobacterial antigens in the sera
      of patients with RA was detected. When statistical analyses was considered, we
      cannot put forward any antigenic fraction alone as the one responsible for the
      increased reactivity.

PMID- 17457439
TI  - Study of the bacterial agents in nosocomial and acquired infections based on the
      blood culture in neonatal intensive care unit of a hospital, north east of Iran.
AB  - OBJECTIVE: To study the distribution of bacterial agents in bloodstream
      infections among hospitalized patients in the neonatal intensive care unit
      (NICU). METHODS: From March 2003 to February 2004, 1341 blood samples were taken
      from hospitalized infants in NICU of Imam Reza Hospital in Mashhad north east of
      Iran. In this study, 6 ml of blood was extracted from the patients having
      septicemia, which was then added to the bottle containing the blood culture
      broth. The bottles were labeled and incubated at 35 degrees C for maximum of 7
      days. RESULTS: The result shows that out of the 202 patients with positive blood
      cultures 109 had gram positive organisms while 93 had gram negative organisms. In
      those with gram-positive bacteria, 73 cases were acquired infection and 36 cases
      were nosocomial infection. These results for gram negative bacteria showed that
      51 cases were due to acquired infection and 42 cases due to nosocomial infection.
      In determining the relation between the rate of death and the type of infection,
      we found that out of 202 patients 83 (41%) died. Of these cases 48 (39%) were due
      to acquired infection and 35 (45%) were due to nosocomial infection. CONCLUSION:
      We conclude that nosocomial bloodstream infection is an important target for the
      most aggressive strategies for prevention and control.

PMID- 17457440
TI  - Effects of intrauterine device and oral contraceptive on vaginal flora and
      epithelium.
AB  - OBJECTIVE: To investigate the microbial and cytopathological changes and genital
      symptoms in oral contraceptive pill (OCP) and intrauterine contraceptive device
      (IUCD) users. METHODS: Included in the study were 34 women using OCP and 34 women
      using IUCD for 24 to 36 months period and 34 women as control group. We conducted
      the study between March to September 2005 in Antakya Maternity Hospital, Turkey.
      Vaginal discharge was subjected to wet mount examination, gram staining, and
      culture. Cervical smears were examined and reported using the Bethesda system as
      reference. RESULTS: In the IUCD group, women with intermediate score was 20.6%,
      while those with bacterial vaginosis was 11.7%. In the OCP group however, women
      with intermediate score was 8.8%, while those with bacterial vaginosis was 5.9%.
      Compared to the control group, these rates were 2.9% for those with intermediate
      score and 2.9% for those with bacterial vaginosis. Escherichia coli vaginal
      colonization increased by 5-fold in the IUCD users (p<0.05). Cervical erosion was
      found in 14.7% of the women using IUCD as compared to the other groups (p<0.05).
      Actinomyces like organisms was detected in 11.7% of the IUCD users (p<0.05).
      CONCLUSION: The use of IUCD clearly alter the normal vaginal flora, although OCP
      appears to have minimal effects on the vaginal microbial flora. The data support
      the hypothesis that IUCD might change cervico vaginal environment, and suggests
      that women with IUCD may be at a higher risk for vulvovaginal infection.

PMID- 17457441
TI  - Effect of low-dose aspirin therapy on implantation rate in women undergoing in
      vitro fertilization cycles.
AB  - OBJECTIVE: To determine the effect of low-dose aspirin on ovarian response,
      implantation and pregnancy rates in patients undergoing in-vitro fertilization
      (IVF) cycles. METHODS: We performed a randomized analysis of 145 infertile women
      with a mean+/-SD age of 29.6 +/- 4.47 years who underwent cycles of IVF. Patients
      received 100 mg of aspirin (n=72) or placebo (n=73) daily. This study was
      conducted in Royan Institute, Tehran, Iran from April 2002 to January 2004.
      Aspirin was started on the 21st of their preceding menstrual cycle and it was
      continued until menstruation or a negative pregnancy test. Pregnant women
      received the medication until 12 weeks of pregnancy. The main outcome measures
      were number of follicles >or=15 mm, number of oocytes retrieved, serum E2 levels,
      cancellation rate, Ovarian Hyperstimulation Syndrome (OHSS) occurrence, number of
      embryos transferred, and implantation and pregnancy rates. RESULTS: There were
      statistically significant differences between the treatment group and the control
      group in the number of follicles (7.4 +/- 4.1 versus 9.0 +/- 4.8) and OHSS
      occurrence (5.6% versus 23.3%) but not in the other measures. CONCLUSION: The
      addition of aspirin low dose (100 mg/daily) to the standard long protocol for
      oocyte retrieval did not improve implantation and pregnancy rates in unselected
      patients undergoing IVF cycles.

PMID- 17457442
TI  - Utilization of antenatal care services by Sudanese women in their reproductive
      age.
AB  - OBJECTIVE: To describe the current antenatal care situation in Sudan with regard
      to routine utilization of antenatal health care services and application of
      tetanus toxoid (TT) vaccination in urban and rural areas. METHODS: The study was
      conducted in Khartoum State, Sudan, between August and December 2002. Interviews
      were held among a representative sample of 400 married women aged 15-49 years
      from both urban and rural localities. Utilization of antenatal care and TT
      vaccine for pregnant women were used as dependent variables while socio-economic
      status, place of resident, women's education, quality of care and walk-time were
      applied as independent variables. RESULTS: Utilization of routine antenatal
      health care services was approximately 5 times and application of TT-vaccination
      was 3.7 times higher in urban women as compared to women in rural areas. A higher
      quality of care (odds-ratio 5.8) and shorter walk-time (odds-ratio 3.1) were
      significantly associated with more utilization of routine antenatal care
      services. Mother's education showed a nearly significant positive relationship
      both with the use of routine antenatal health care service (odds-ratio 2.1).
      CONCLUSION: Results suggest that public health care policy should focus on 1.
      developing more high quality primary health care facilities for routine antenatal
      care and TT-vaccination in rural areas, and 2. development and implementation of
      mass-media and community education for pregnant women on the need for routine
      antenatal care and TT-vaccination.

PMID- 17457443
TI  - Hearing threshold in patients with chronic renal failure.
AB  - OBJECTIVE: To determine the pattern of hearing loss among patients with chronic
      renal failure (CRF). METHODS: This is a case control study carried out jointly by
      the Otorhinolaryngology and Nephrology Departments of the University College
      Hospital Ibadan, Nigeria between December 2004 and March 2006. Consecutive CRF
      patients who satisfied the inclusion criteria were recruited, the patients had
      not had hemodialysis prior to inception of the study. Parameters like age,
      gender, duration of illness and blood pressure were recorded and pure tone
      audiometry was carried out. The data was analyzed using the Statistical Package
      for Social Sciences. RESULTS: Thirty-three CRF patients and 28 healthy controls
      (34 males and 27 females) were used. The age range was 16-72 years, mean of 45.30
      (SD 16.20). Sensorineural hearing loss was found in 67% of CRF and 32% of
      controls. The mean hearing threshold of CRF was 47.42 (SD 18.55) while the
      controls was 35 db, unpaired t-test (value -5.155) and Pearson correlation
      p=0.0008, r=0.614 showed the difference was significant. There was a correlation
      between duration of renal disease and hearing threshold p=0.00387 (r=0.73). There
      was no correlation between the hearing threshold and the diastolic blood pressure
      p=0.056 dosage of diuretics p=-0.155 (r=0.12) and creatinine level of the
      patients p=0.35 (r=0.31). CONCLUSION: Sensorineural hearing loss is common among
      patients with CRF and related to the duration of renal disease, we recommend
      periodic audiological assessment incorporated in the care of these patients.

PMID- 17457444
TI  - Level of health awareness of Saudi patients on renal replacement therapy.
AB  - OBJECTIVE: To assess health awareness in patients on renal replacement therapy
      (RRT) in Saudi Arabia. METHODS: This is a cross-sectional survey using a 22-item
      questionnaire in 143 randomly selected adult RRT patients [40 on hemodialysis
      (HD), 61 on peritoneal dialysis (PD) and 42 with renal transplant (TX)]. The
      study was carried out at King Abdul-Aziz Medical City, Riyadh in April 2006. The
      questionnaire was designed to evaluate patients' knowledge in 5 areas: 1. causes
      of renal failure, 2. biology of the kidneys, 3. symptoms of kidney disease, 4.
      therapeutic options available, 5. national kidney patients support facilities.
      The association between the level of awareness (the percentage of correct
      answers) to different demographic factors was assessed. RESULTS: Three fifths of
      the patients had less than secondary education. The average mark for correct
      responses of all patients was 45.9% with a highest (58%) for the category on
      biology of the kidney and lowest (36.8%) for national kidney patients support
      facilities. The PD group had the highest score (54.4%) followed by HD (44.3%) and
      finally TX (35.1%). CONCLUSION: The level of our patients; health awareness is
      lower than satisfactory. Level of education seems to be a contributory factor.

PMID- 17457445
TI  - Survey of operative outcome for aortic dissection.
AB  - OBJECTIVE: To survey the results of operative outcome for aortic dissection.
      METHODS: A retrospective study on 46 patients, admitted for operation in Shahid
      Madani Heart Hospital in Tabriz, Iran from 1994-2003. A questionnaire was used
      for collecting data. Statistical analysis was performed and was carried out
      through a descriptive statistical methods. RESULTS: We included 30 males (65%)
      and 16 females (35%). Seven (15.2%) died in the operating room before surgery,
      while 39 patients (59% male and 41% female) underwent surgery. The mean age of
      patients was 48.9 +/- 2.3 years old. Pre-operative diagnosis was carried out by
      transesophageal echocardiography and angiography. All patients were operated in
      an emergency situation. In 42% of patients aortic valve replacement (AVR) with
      ascending aorta was replaced. In 24% only the ascending aorta was replaced, and
      in 10% the aortic valve was repaired with acute aortic dissection. In 10% of
      patients, the ascending aorta with aortic arch was replaced. Four patients (14%)
      had distal aortic dissection and replacement. Major complications were hemorrhage
      (31%) and respiratory failure (13.8%). A total of 20.7% died in hospital, and
      only 21 patients (45.5%) could be followed for 10 years. CONCLUSION: Acute aortic
      dissection is a fatal disease. With early diagnosis and surgical intervention, we
      can save approximately 75% of patients with very good functional class and
      survival in the mid term.

PMID- 17457446
TI  - Management of omphalocele using the sac as supportive material.
AB  - OBJECTIVE: To document retrospectively the outcome of a newly modified procedure
      for closure of large omphalocele, where the sac was conserved and used as
      autogenous supportive material. METHODS: The medical records of 10 patients with
      omphalocele major admitted to Al-Noor Specialist Hospital in Makkah, Kingdom of
      Saudi Arabia in the last 15 years, October 1990 to October 2005, were
      retrospectively reviewed. The defects were considered by the same treating
      surgeon too big to be closed primarily so the sac was preserved to reduce the
      contents gradually. RESULTS: In the first stage, complete reduction was achieved
      in all the cases followed by second stage, the surgical closure. There was no
      mortality related to this intervention. CONCLUSION: This proposed technique is
      safe, simple and effective for the treatment of large omphalocele.

PMID- 17457447
TI  - Evaluation of independent prognostic importance of hyperuricemia in hospital
      death after acute myocardial infarction.
AB  - OBJECTIVE: To evaluate the role of hyperuricemia (serum uric acid level greater
      than 7 mg/dl) as an independent short term (in hospital) prognostic factor after
      acute myocardial infarction (AMI). METHODS: Included in the study were 2218
      patients who were hospitalized with well established AMI from June 1996 through
      to December 2002 in the Coronary Care Unit of Ekbatan General Hospital, Hamedan
      University of Medical Sciences, Iran. All patients with exclusive criteria, were
      omitted from study. Furthermore, frequency of hyperuricemia in patients (N=59)
      who expired after AMI was compared with patients (N=104) whom were discharged
      from the hospital after AMI. RESULTS: Frequency of hyperuricemia was measured
      according to the extension of myocardial necrosis (as the most important
      prognostic risk factor) based on serum creatine phosphokinase level greater or
      less than 2000 IU, which was 13.3% and 20.7% in the case group, and 9.5% and 9.7%
      in the controls, respectively. CONCLUSION: These findings indicate that
      hyperuricemia is not an independent prognostic risk factor in hospital death
      after AMI.

PMID- 17457448
TI  - Idiopathic intracranial hypertension. Atypical presentation.
AB  - OBJECTIVE: To describe the clinical features of 5 patients with rare atypical
      presentation of idiopathic intracranial hypertension (IIH), and propose the
      possible mechanism of this atypical presentation. METHODS: We carried out a
      retrospective study of 5 patients admitted at King Khalid National Guard
      Hospital, Jeddah, Kingdom of Saudi Arabia with IIH during the period from January
      2001 to December 2005. All were females with their age ranges from 24 to 40
      years. The clinical presentations, and the laboratory and imaging studies were
      analyzed. The opening pressures of the lumbar puncture tests were documented.
      RESULTS: All patients were presented with headache. One had typical pain of
      trigeminal neuralgia, and one with neck pain and radiculopathy. Facial diplegia
      was present in one patient, and 2 patients had bilateral 6th cranial neuropathy.
      Papilledema was present in all patients except in one patient. Imaging study was
      normal in all patients, and they had a very high opening pressure during lumbar
      puncture, except in one patient. All patients achieved full recovery with medical
      therapy in 6 to 12 weeks with no relapse during the mean follow up of 2 years.
      CONCLUSION: Atypical findings in IIH are rare and require a high index of
      suspicion for early diagnosis.

PMID- 17457449
TI  - Adiposity and physical activity levels among preschool children in Jeddah, Saudi
      Arabia.
AB  - OBJECTIVE: To assess the levels of adiposity and physical activity among Saudi
      preschool children from Jeddah. METHODS: Participants included 224 Saudi
      preschool children, randomly selected from public and private preschools in
      Jeddah during April and May of 2006, using a multistage stratified sampling
      technique. Measurements included weight, height, body mass index, triceps and
      subscapular skinfolds, fat percentage, fat mass (FM), fat-free mass (FFM), FM
      index (FMI) and FFM index (FFMI), time spent watching television and physical
      activity levels using electronic pedometer for 3 continuous days during weekdays.
      RESULTS: The fat content averaged 20.6% of body weight, while the prevalence of
      obesity was 10.8%. There were significant gender differences in fat percentage,
      FM, FFM, FMI, and FFMI. The mean value for pedometer-determined steps counts for
      the preschool children was 6773.2 steps per day. Boys were significantly more
      active than girls. Only 22.4% of the preschool children had 10,000 steps or more
      per day. There were no significant age differences in skinfolds measurements, fat
      percentage, FMI, FFMI, central obesity or daily steps counts. Television viewing
      time increased by 22.5% from age 4 to age 6. Compared to non-obese, obese
      preschool children were significantly heavier, taller and had higher values for
      all adiposity indices and television viewing time. CONCLUSION: A considerable
      proportion of Saudi preschool children is obese and even a greater proportion is
      physically inactive. Obesity and physical inactivity represent major risks for a
      number of non-communicable diseases, and an early intervention is most
      appropriate.

PMID- 17457450
TI  - High prevalence of osteoporosis in Saudi men.
AB  - OBJECTIVE: To determine the prevalence of osteoporosis in healthy Saudi men.
      METHODS: We randomly recruited 429 Saudi men from the community. The recruited
      Saudi men were subjected to an interview to reveal their lifestyle parameters,
      calcium intake and level of activity. Bone densitometry was assessed at lumbar
      spine (L1-4) and the femoral neck. The dual x-ray absorptiometry (DXA) scan was
      carried out in the Nuclear Medicine at King Khalid University Hospital, Riyadh,
      Saudi Arabia from September 2002 to December 2004. The World Health Organization
      definition of low bone mineral density was used. RESULTS: Poor oral calcium
      intake and low level of daily activity were noted. The overall prevalence of
      osteopenia for the lumbar spine in the whole group was 35.7% while osteoporosis
      was present in 21.4% of the subjects. In the femoral neck, osteopenia was noted
      in 38% and osteoporosis in 11.4%. When either lumbar spine or femoral neck
      osteoporosis is used for diagnosis, the prevalence of osteoporosis rises to
      23.5%. Within the whole group, osteopenia and osteoporosis were more common in
      individuals above the age of 50 than those below 50 years old. CONCLUSION: Low
      bone mineral density occurs with high frequency in Saudi men. Lumbar spine
      appears to be affected to a higher degree. The reason for the high prevalence of
      osteoporosis in Saudi men is unclear. Possible underlying causes include
      nutritional, life style and genetic factors.

PMID- 17457451
TI  - Collision tumor-concurrent involvement of Virchow's lymph node by Hodgkin's
      disease and metastatic gastric adenocarcinoma. A Troisier's sign and more?
AB  - We describe the case of a 59-year-old Caucasian male who presented to the
      outpatient clinic with intractable hiccups, upper abdominal pain, repeated bouts
      of vomiting, and stiff neck. Physical examination revealed a cachectic male with
      pallor, with enlarged left supraclavicular Virchow's lymph node and
      hepatosplenomegaly. Histologic examination of the excised lymph node revealed
      simultaneous presence of 2 malignant processes, nodular sclerosing classical
      Hodgkin's lymphoma and metastatic adenocarcinoma. Subsequent investigations of
      the patient, revealed the presence of gastric adenocarcinoma. Although factors
      governing the coexistence and the possible order of appearance of the 2
      pathologies in the present case remain unknown, attempts are made to elucidate
      the pathogenetic mechanisms that led to their existence.

PMID- 17457452
TI  - Primary hyperparathyroidism. A rare cause of spinal cord compression.
AB  - We report a case of a 62-year-old postmenopausal hypertensive lady who was
      treated for osteoporosis with calcium and Vitamin D. She presented with
      progressive lower limb weakness and paresthesia with sensory level at T4.
      Investigations revealed high parathyroid hormone 1152 ng/dl, calcium 10.9 mg/dl,
      and low phosphorus of 2.4 mg/dl after stopping calcium supplement. Chest x-ray
      showed an expansile mass lesion of the right 6th rib confirmed by chest CT.
      Thoracic MRI showed a mass lesion extending from the T3 vertebral body and
      compressing the spinal cord. There were multiple lytic lesions of the scalp,
      ribs, femur, and pelvis suggesting metastatic lesions. A neck ultrasound and
      SESTA MIBI parathyroid scan confirmed a right lower parathyroid adenoma. Excision
      biopsy of the rib lesion confirmed a vascular lesion with features of brown tumor
      BT. Decompression surgery of the thoracic spine was performed, and the
      histopathology confirmed BT. Two weeks later the patient underwent right
      parathyroidectomy that proved to be a parathyroid adenoma. She showed a
      remarkable improvement in her clinical condition and there were some regression
      of the bony lesions observed 12 months post parathyroidectomy. This case should
      alert physicians to the association of multiple brown tumors in PHPT and that the
      presentation may be an aggressive one mimicking metastasis, patients with
      osteoporosis warrant at least calcium profile to rule out a secondary cause.

PMID- 17457453
TI  - Invasive squamous cell carcinoma of the eyes in patients with epidermodysplasia
      verruciformis.
AB  - We described 3 male patients with epidermodysplasia verruciformis seen in the
      Department of Dermatology and Venereology, Baghdad Teaching Hospital; their ages
      were 25, 30 and 34 years subsequently. They developed frequent multiple basal and
      squamous cell carcinoma, all of them had periorbital squamous cell carcinoma that
      invaded the orbit and ended with enucleation of their eyes. All available
      therapeutic measures failed to inhibit the progressiveness of these tumors. Great
      awareness and early management must be performed regarding any periorbital lesion
      in epidermodysplasia verruciformis patients.

PMID- 17457454
TI  - Male genital self-amputation in the Middle East. A simple repair by anterior
      urethrostomy.
AB  - Genital self-mutilation, whether partial or complete, is a rare condition, which
      usually occurs in psychotic patients and occasionally has a religious background.
      The initial management of complete genital self-mutilation usually involves a
      formation of perineal urethrostomy or a more complex procedure to form a short
      penile stump. Here, we present a case of complete genital self-mutilation in a
      psychotic male who was managed with simple urethral spatulation to form an
      anterior urethrostomy.

PMID- 17457455
TI  - Ectopic pregnancy after bilateral salpingectomy.
AB  - Ectopic pregnancy is a life threatening condition and is a major event in a
      woman's reproductive life. We report herein an unusual case of repeated ectopic
      pregnancy even after the excision of both fallopian tubes with a deleterious
      consequences and a near miss. This case teaches us a lesson not to forget ectopic
      pregnancy. The lady in this report underwent in vitro fertilization treatment
      cycle due to absence of both fallopian tubes as consequence of previous ectopic
      pregnancy and a hydrosalpinx; she conceived successfully but unfortunately the
      pregnancy was another ectopic pregnancy.

PMID- 17457456
TI  - Pure red cell aplasia associated with thymic follicular hyperplasia.

PMID- 17457457
TI  - An Arab tradition could lead to a disaster in diabetic patients.

PMID- 17457458
TI  - Screening for hOGG1 S326C variant in normal Saudi population.

PMID- 17457459
TI  - Is Saudi Arabia a fertile land for exchanging infectious diseases?

PMID- 17457460
TI  - Spontaneous recovery of propylthiouracil-induced fulminant hepatic failure in an
      8-year old child.

PMID- 17457461
TI  - Rimonabant as potential treatment for the neglected epidemic of diabetes in the
      Middle East and Arabian Peninsula. Implication for prevention.

PMID- 17457462
TI  - Five-year surveillance of chickenpox in Qassim, Central Saudi Arabia.

PMID- 17457463
TI  - Chronic unilateral nasal obstruction in children.

PMID- 17457464
TI  - Treatment of alopecia areata by topical diclofenac sodium gel in comparison to
      benzoyl peroxide. A novel single blind therapeutic clinical trial.

PMID- 17457465
TI  - Post hemorrhoidectomy pain. A randomized controlled trial.

PMID- 17457466
TI  - Surgical treatment of chronic sacrococcygeal pilonidal sinus. Open method versus
      primary closure.

PMID- 17457467
TI  - An introduction into proteomics and its clinical applications.
AB  - The completion of the human genome project has marked the official start of the
      post-genomic era. Due to limitations in DNA and RNA studies, the advent of
      proteomics, or large-scale analysis of proteins, is considered a crucial
      consequence and a chief player of post-genomic initiatives. An immediate goal of
      proteomic studies is the understanding of proteins including their expression,
      function, interaction, and structure with an endpoint of discovery of protein
      biomarkers. Such biomarkers can be used in detection, prognostication, and
      treatment of diseases. However, the challenge of studying complete sets of
      cellular proteins, or proteomes, is driving the development of newer
      technologies. In this review, a discussion of proteomic biotechnologies and their
      clinical applications is offered. The main techniques covered are the 2
      dimensional polyacrylamide gel electrophoresis, mass spectrometry, surface
      enhanced laser desorption ionization mass spectrometry, and protein microarrays.
      These tools have been successfully utilized in analyzing human and other
      biological samples in discovery of biomarkers. Recent advancement in proteomics
      has added and will continue to add valuable information to our knowledge-base of
      the human biological system.

PMID- 17457468
TI  - Functioning free muscle transplantation for restoring upper extremity function.
AB  - Functioning free muscle transplantation FFMT is now an important procedure in
      several fields of reconstructive surgery. In this article, the progress of FFMT
      in restoring upper extremity function, including essential aspects like
      indications, preoperative examination, donor muscle selection, donor nerve
      selection, operative technique, tension of muscle at suturing, postoperative
      functional assessment, and changes of the transferred muscle after operation are
      discussed in detail.

PMID- 17457469
TI  - Expression of CXC chemokine IP-10/Mob-1 by primary hepatocytes following heat
      shock.
AB  - OBJECTIVE: To examine the expression of chemokine IP-10/Mob-1 of hepatocytes in
      responses to the stress imposed during isolation by collagenase perfusion.
      METHODS: This study was performed in the Faculty of Life Sciences University of
      Manchester during 2001-2005. We employed western and northern blotting analysis
      to detect IP-10/Mob-1 in isolated and cultured hepatocytes in response to
      isolation stresses and under heat shock stimulation in this project. RESULTS: We
      showed that the ELR-CXC chemokine, IP-10/Mob-1 is secreted from isolated rat
      hepatocytes immediately after isolation and early during culture and IP-10/Mob-1,
      expression by hepatocytes was also stimulated in response to heat shock.
      CONCLUSION: It seems that hepatocytes mimic the experiences of liver injury in
      vivo such as during stress, trauma, or after insults, and therefore, produce
      stress related agents like IP-10/Mob-1 chemokine to overcome such a injurious
      condition following isolation and heat shock stimulation. This study also
      provides a useful model to study the regulation of expression of this chemokines
      in vitro.

PMID- 17457470
TI  - Estimation of transforming growth factor-beta 1 as a marker of renal injury in
      type II diabetes mellitus.
AB  - OBJECTIVE: To evaluate the serum transforming growth factor-beta 1 level in type
      II diabetic patients with diabetic nephropathy (DN) and to assess its use as a
      marker of renal injury in type II diabetes. METHODS: Sixty patients with type II
      diabetes mellitus (DM), who attended the outpatient internal medicine clinic in
      Cairo University Hospital, Egypt from January 2003 to March 2003, were the
      subjects of the present study and compared to 10 healthy age- and gender- matched
      control subjects They were divided into 6 major groups according to degree of
      metabolic control, as determined by glycosylated hemoglobin (HbA1c), the rate of
      urinary albumin excretion (UAE) and serum creatinine level. Serum transforming
      growth factor-beta 1 level was assessed by enzyme linked immunosorbent assay
      (ELISA). RESULTS: Serum transforming growth factor-beta 1 level was significantly
      increased in micro albuminuric (UAE 20-200 ug/minute), macro albuminuric (UAE
      >200 ug/minute) and overtly nephropathic diabetic patients with renal impairment
      compared to healthy controls (p<0.05). In addition, serum transforming growth
      factor-beta 1 level was significantly increased in type II diabetic patients with
      poor glycemic control (HbA1c >7.6%) compared to patients with good glycemic
      control (HbA1c 5.5-7.6%). Serum transforming growth factor-beta 1 level was
      significantly increased in hypertensive DM patients compared to normotensive DM
      patients (p<0.05). There was a strong correlation between serum transforming
      growth factor-beta 1 level and HbA1c, blood urea, serum creatinine and 24-hour
      urinary protein excretion (p<0.01). CONCLUSION: Our data strongly support the
      hypothesis that hyperglycemia may trigger the activation of transforming growth
      factor-beta 1 which in turn mediates progressive renal damage in type II DM.
      Increased serum transforming growth factor-beta 1 may be useful as a marker of
      diabetic renal disease as it shows a close association with the parameters of
      renal injury in type II diabetes.

PMID- 17457471
TI  - Developmental variations and clinical importance of the fetal thyroid gland. A
      morphometric study.
AB  - OBJECTIVE: To investigate the morphologic structures and developmental anomalies
      of the thyroid gland in human fetuses. METHODS: This study performed in the
      Department of Anatomy, Meram Faculty of Medicine between February and April in
      2002. Fetuses were obtained from the Gynecology Department of the Meram Faculty
      of Medicine, Selcuk University, and Dr. Faruk Sukan Maternity Hospital (Konya,
      Turkey). Sixty spontaneously aborted fetuses (30 boys and 30 girls) between the
      ages of 13.5th and 32.5th weeks, which had no detectable anomalies, were
      evaluated. The gland was dissected under the microscope. The location of the
      gland was determined according to the tracheal ring levels and laryngeal
      cartilage levels. The length, width and thickness of both lobes and isthmus of
      the gland were measured and then, the developmental anomalies were noted. The
      obtained data were statistically analyzed by Least Squares in variant analysis.
      RESULTS: Although there was no significant difference regarding to the gender for
      all parameters except in width of the right lobe (p<0.05), difference in the
      length and width of lobes and the length of isthmus between trimesters was
      significant (p<0.05). All measured parameters were increasing with advancing
      gestational age. The pyramidal lobe was observed in 18.3% of the cases.
      CONCLUSION: Normal dimensions and developmental anomalies of the fetal thyroid,
      which was shown in this study, may provide useful information for the prenatal
      diagnosis and in-utero treatment of thyroid dysfunctions.

PMID- 17457472
TI  - Restriction fragment length polymorphism of virulence genes cagA, vacA and ureAB
      of Helicobacter pylori strains isolated from Iranian patients with gastric ulcer
      and nonulcer disease.
AB  - OBJECTIVE: To investigate the distribution of different genotypes of major
      virulence factors cagA, vacA and ureAB among Helicobacter pylori (H. pylori)
      strains isolated from patients with ulcerative and nonulcerative diseases.
      METHODS: This study was performed in Clinical Microbiology Research Center,
      Shiraz University of Medical Sciences, Shiraz, Iran, during November 2004 to
      October 2005. Sixty-five H. pylori strains, 30 from patients with gastric ulcer
      (ulcerative disease) and 35 from patients with gastritis (nonulcerative disease)
      were analyzed by polymerase chain reaction (PCR) to investigate the presence of
      cagA, vacA and ureAB genes. The amplified fragments were then digested with the
      restriction enzymes HaeIII (for ureAB) HinfI (for cagA) and HphI (for vacA).
      RESULTS: We found a significantly higher prevalence of vacA-positive strains in
      ulcerative disease (UD) than that in nonulcerative disease (NUD) patients
      (p<0.05). Restriction fragment length polymorphism (RFLP) analysis revealed 2
      different patterns for cagA gene. The prevalence of pattern beta with 3 bands was
      significantly higher in both groups of patients. HaeIII digestion resulted in a
      strictly homogeneous pattern for 83.33% of the vacA+ strains isolated from the
      patients with UD. This pattern was significantly associated with UD status
      (p<0.05). The ureAB polymorphism analysis revealed 10 distinguishable DNA banding
      patterns among them the pattern named ureAB 5a was the most prevalent (47.61%) in
      all isolates. No association between a specific DNA pattern and clinical disease
      was observed for cagA and ureAB (p>0.05). CONCLUSION: It seems that in our
      patients, the presence of cagA gene may not necessarily be a risk factor for
      ulcer disease, while a homologous genotype of vacA appears to be associated with
      an increase risk of UD development. Lastly, despite the existence of a high
      degree of genomic variability within ureAB, conserved DNA banding profiles are
      distributed in our areas.

PMID- 17457473
TI  - Supportive presumptive diagnosis of Plasmodium vivax malaria. Thrombocytopenia
      and red cell distribution width.
AB  - OBJECTIVE: To evaluate hemoglobin, leukocyte, platelet counts and red cell
      distribution width values during acute vivax malaria. METHODS: This study, which
      comprises 90 symptomatic vivax malaria patients compared with 52 healthy
      controls, investigated hemoglobin, leukocyte, platelet counts and red cell
      distribution width values during acute disease prior to the treatment in vivax
      malaria, from May 2002 to December 2004 in Adana, Cukurova region, located in the
      southern part of Turkey, along the Mediterranean coast. RESULTS: Mean values for
      hemoglobin, leukocyte and platelet counts in the vivax malaria group in our study
      were found to be significantly lower in comparison to the control group. Anemia
      and thrombocytopenia were also observed in the malaria group while not in the
      control group (p<0.05, p<0.0001). Mean red cell distribution width values were
      found to be significantly higher in the malaria group (p<0.0001). CONCLUSION: Our
      findings indicated that routinely used laboratory findings such as low
      hemoglobin, leukocyte or platelet counts and especially high red cell
      distribution width values could present a more supportive clue in the diagnosis
      of vivax malaria in endemic areas.

PMID- 17457474
TI  - Efficacy of hepatitis B vaccine in susceptible spouses of chronic hepatitis B
      virus infected individuals at the time of marriage.
AB  - OBJECTIVE: To evaluate the efficacy of hepatitis B virus (HBV) vaccine in
      susceptible spouses at the time of marriage. METHODS: From April 2003 to December
      2005, 60 cases of susceptible wives of infected husbands and 32 cases of
      susceptible husbands of the infected wives in Babol north of Iran, received
      recombinant hepatitis B (HB) vaccine at the time of marriage followed with the
      second and third doses at 1, and 6 months. Post vaccination tests for hepatitis B
      surface antigen (HBsAg), anti-HBs and anti-hepatitis B core (HBc) were assessed 2
      months of the later dose. The HBs antibody levels of > or = 10 mIU/ml was
      considered to be protective. Those with anti-HBs levels of <10 mIU/l received the
      second series of HBV vaccination. RESULTS: The mean age of the infected husbands
      was 26.4 +/- 6 years and for infected wives were 22.7 +/- 4.7 years. Seventy
      (76.1%) cases were HBsAg and anti-hepatitis B e (HBe) positive. Among the
      recipients of vaccine, the mean age of females was 19 +/- 3.8 years and in males
      was 25.2 +/- 4.8 years (p=0.007). The HBs antibody levels of > or = 10 mIU/ml
      were detected in 79 (85.9%) cases. The HBs antibody levels of >100 mIU/ml were
      developed in 76.7% males and in 75% females (p=0.430). Twelve (13%) cases were
      non-responder and among them 11 (91.7%) cases responded to the second course of
      HBV vaccination. The HBs and HBc antibodies were developed in one case.
      CONCLUSION: This study shows that administration of hepatitis B vaccine at the
      time of marriage prevents the transmission of hepatitis B virus in susceptible
      spouses.

PMID- 17457475
TI  - Trends of drug resistant Mycobacterium tuberculosis in a tertiary tuberculosis
      center in Iran.
AB  - OBJECTIVE: To determine the drug resistance pattern to first line antituberculous
      drugs in National Research Institute of Tuberculosis and Lung Disease and to
      compare resistant rates with previous studies. METHODS: An anterograde cross
      sectional study was performed. The study includes all adults with documented
      pulmonary tuberculosis (TB) that were hospitalized in National Research Institute
      of Tuberculosis and Lung Disease in Tehran, from June 2003 to September 2004.
      Demographic characteristic, TB categories, and drug susceptibility test results
      were recorded. Two previous studies regarding drug susceptibility in Iran were
      selected as historical controls. RESULTS: One hundred and ninety-six new cases
      and 68 previously treated patients were enrolled in the study. The strains of 61%
      of new patients and 21% of previously treated patients were fully sensitive to
      all drugs. The most common resistance was streptomycin (27%) followed by
      isoniazid (23%) in new cases. Multiple drug resistant strains were noted in 2.6%
      (95% CI 0.8% to 5.8%) of new cases versus 56% (95% CI 43% to 68%) in previously
      treated group. The frequency of primary drug resistance to isoniazid was 9.8%-15%
      or streptomycin 9.8%-13% in the previous studies (p<0.00001). CONCLUSION: While
      these rates may not reflect the true prevalence of drug resistance on a national
      scale, it does partially demonstrate some defects in the existing tuberculosis
      control program. The significant increase of isoniazid and streptomycin
      resistance in the last few years would present a serious challenge to effective
      management of TB.

PMID- 17457476
TI  - The post-antibiotic effects of linezolid against Gram-positive pathogens.
AB  - OBJECTIVE: To investigate the post-antibiotic effect (PAE) of linezolid against
      methicillin-resistant and -susceptible staphylococci, vancomycin-resistant and 
      susceptible enterococci. METHODS: Clinical strains of Staphylococcus aureus (S.
      aureus), Staphylococcus epidermidis (S. epidermidis) and Enterococcus faecalis
      (E. faecalis) were isolated from hospitalized patients at Ege University Medical
      Faculty Hospital between June and September 2005. This study was made between
      September and December 2005. The PAE of linezolid was determined at the minimum
      inhibitory concentration (MIC) and 4 times the MIC concentrations for 60 minutes
      in Mueller-Hinton Broth (MHB). The duration of the PAE was obtained by following
      the recovery of bacterial growth in antibiotic free MHB measured colony forming
      units on Mueller-Hinton agar. RESULTS: All the straines were susceptible to
      linezolid. The PAE was greater at 4 times the MIC (0.5 - 2.4 hours) that at the
      MIC (0 - 1.7 hours) for linezolid against all organisms tested. The PAE for
      linezolid was slightly higher against E. faecalis strains than other organisms.
      CONCLUSION: In this study, it was demonstrated that linezolid had a moderate in
      vitro PAE against S. aureus, S. epidermidis and E.faecalis strains.

PMID- 17457477
TI  - Hepatic hydatid disease in children and adults living in different areas in
      Turkey.
AB  - OBJECTIVE: To compare the clinical features of the hepatic hydatid disease in the
      operated children and adults living in the east and west part of Turkey. METHODS:
      Between January 2001 and May 2005, 105 patients were operated with the diagnosis
      of hepatic hydatid cyst in Trakya and Yuzuncu Yil University Hospitals, Turkey.
      The patients (n=105) were retrospectively evaluated in 4 groups; Edirne Ch: (18
      children under 18 year-old) and Edirne Ad: (20 adults) were from Edirne, Van Ch:
      (22 children under 18 year-old) and Van Ad: (44 adults) from Van. The patients in
      each group were analyzed according to their clinical and radiological findings.
      RESULTS: The frequency of hepatic hydatid cysts in children was significantly
      higher in boys in Edirne Ch group and in girls in Van Ch group (p<0.05). In
      adults, the disease was also seen significantly higher in males in Edirne Ad
      group and females in Van Ad group (p<0.05). There were no difference symptoms of
      the disease, concomitant extra hepatic cysts and total cyst number in children
      and adults in the same region (p>0.05). The number of huge hepatic cysts and
      history of contact with animal were more common in children and adults living in
      Van. CONCLUSION: While the course of hepatic hydatid disease has the similar
      clinical features among the children and adults in the same region, remarkable
      regional differences have been found on it.

PMID- 17457478
TI  - Prevalence of physical activity and inactivity among Saudis aged 30-70 years. A
      population-based cross-sectional study.
AB  - OBJECTIVE: To assess physical activity levels among Saudi adults, and to examine
      the relationships of physical activity with body mass index (BMI), waist
      circumference (WC) and obesity prevalence. METHODS: Data taken from the Coronary
      Artery Disease in Saudis Study which is a National Epidemiological Health Survey
      carried out between 1995 and 2000. Participants included 17395 Saudi males and
      females aged 30-70 years, selected randomly using a multistage stratified cluster
      sampling technique. Leisure-type and sport-related physical activities including
      walking were assessed using an interviewed-administered questionnaire. The
      activities were classified into five intensity categories and assigned metabolic
      equivalents (MET) according to the compendium of physical activity. Based on the
      intensity, duration and frequency of physical activity, subjects were classified
      into active or inactive category. RESULTS: Inactivity prevalence (96.1%) was very
      high. There were significantly (p<0.001)) more inactive females (98.1%) than
      males (93.9%). Inactivity prevalence increases with increasing age category,
      especially in males, and decreases with increasing education levels. Inactivity
      was the highest in the central region (97.3%; 95% CI = 96.8-97.8%) and the lowest
      in the southern region of Saudi Arabia (94.0%; 95% CI = 93.2-94.8%). Further,
      active individuals exhibited lower values of BMI and WC. CONCLUSION: These
      findings reveal the sedentary nature of Saudi population. The overwhelming
      majority of men and women did not reach the recommended physical activity levels
      necessary for promoting health and preventing diseases. The high prevalence of
      inactivity among Saudis represents a major public health concern.

PMID- 17457479
TI  - Perception of the role of inhaled corticosteroids and factors affecting
      compliance among asthmatic adult patients.
AB  - OBJECTIVE: To examine the patient characteristics linked with reduced adherence
      to inhaled corticosteroids (ICS) use. METHODS: A prospective study of adult
      asthmatic patients who were prescribed with ICS and are under regular follow-up
      at the pulmonary outpatient clinics between June 1st, and December 31st, 2001, at
      King Fahad National Guard Hospital in Riyadh. All patients underwent structured
      interviews with an investigator. RESULTS: Included in the study were 334
      patients. Thirty eight percent (38%) of the patients reported irregular use of
      ICS. Factors associated with irregular ICS use were a negative perception of the
      role of ICS (p=0.03) and less than high school education (p=0.03). Almost 50%
      (169/334) of all patients had concerns regarding ICS safety resulting in reduced
      willingness to use them. These concerns were again significantly related to the
      level of education and the patient's attitude to ICS. Among the most common fears
      hindering regular ICS use were their potential to lead to addiction (60%) and
      worry from steroid side effects (41%). CONCLUSION: The result of this study
      raises the importance of patient's education and the importance of treatment of
      those involved in asthma care to educate the patient and discuss with them the
      role of asthma medications, particularly ICS, and to correct common fears and
      misconceptions.

PMID- 17457480
TI  - Risk factors of pulmonary thromboembolism in patients from a university hospital.
AB  - OBJECTIVE: To investigate the impact of risk factors in the diagnosis of
      pulmonary thromboembolism. METHODS: This was a retrospective study of 295
      patients with suspicion of pulmonary embolism (PE), of whom 154 were referred
      from outpatient and 141 from inpatient departments for a period of 24 months
      (2000-2001) in Hacettepe University Hospital in Ankara. RESULTS: Pulmonary
      thromboembolism was diagnosed in 71 patients (24.1%) with high probability
      ventilation/perfusion scintigraphy. Chronic renal failure, trauma, history of
      pulmonary thromboembolism and type of care were significantly associated with
      pulmonary thromboembolism, after adjusting for age and gender. CONCLUSION: This
      retrospective study revealed that clinicians should keep PTE in mind, especially
      in the presence of risk factors. Ventilation/perfusion scintigraphy has been the
      procedure of choice for the assessment of patients with suspected PE.

PMID- 17457481
TI  - Risk factors for diabetic retinopathy in Kuwaiti type 2 diabetic patients.
AB  - OBJECTIVE: To determine the risk factors associated with diabetic retinopathy in
      Kuwaiti subjects with type 2 diabetes. METHODS: Kuwaiti subjects with type 2
      diabetes (n=165) attending the Diabetic Clinic at Al-Sabah Hospital, Kuwait
      between October 2000 and March 2005 were screened for diabetic retinopathy.
      RESULTS: Any diabetic retinopathy was found in 40% while 20.6% had sight
      threatening retinopathy. Mild NPDR was present in 21.2%, moderate to severe non
      proliferative diabetic retinopathy (NPDR) in 7.9%, and proliferative diabetic
      retinopathy (PDR) in 3.0%. Maculopathy was present in 10.3% and 7.9% of the
      patients were photocoagulated. Compared to those without retinopathy, diabetic
      patients with any retinopathy were significantly older (51.7 +/- 10.3 versus 47.2
      +/- 9.5 years; p<0.005), had longer duration of diabetes (13.1 +/- 6.3 versus 4.7
      +/- 5.4 years; p<0.0001), higher systolic blood pressure (142.9 +/- 23.0 versus
      130.3 +/- 20.2; p<0.0001) and poor glycemic control (Hemoglobin A1c = 10.1 +/-
      2.4 versus 8.9 +/- 2.3; p<0.005). The prevalence of hypertension and nephropathy
      was significantly higher in patients with any retinopathy than those without
      retinopathy (70.8% versus 49.5%; p<0.01 and 64.4% versus 30.8%; p<0.0001)
      respectively. Longer duration of diabetes and presence of nephropathy was the
      most significant independent factors associated with any retinopathy and sight
      threatening retinopathy. Treatment with sulphonylurea or insulin, and poor
      glycemic control were other significant independent factors associated with any
      retinopathy. CONCLUSION: Longer duration of diabetes, presence of nephropathy,
      glycemic control and mode of treatment were the most significant independent risk
      factors of diabetic retinopathy. However, a population-based study is warranted
      to identify the risk factors, as well as the prevalence of diabetic retinopathy.

PMID- 17457482
TI  - Type 1 diabetes-related epidemiological, clinical and laboratory findings. An
      evaluation with special regard to autoimmunity in children.
AB  - OBJECTIVE: To evaluate our data related with epidemiologic features, clinical
      presentation, and laboratory findings in children with type 1 diabetes mellitus
      (DM1) and to compare specific characteristics of immune-mediated subtype (DM 1A)
      with idiopathic one (DM 1B). METHODS: We classified 115 children with DM1
      according to the presence (DM 1A, n=77) or absence (DM 1B, n=38) of diabetes
      related autoantibodies in Akdeniz University Hospital, Turkey from January 2000
      to December 2005. RESULTS: A total of 43 patients (37%) in the whole group, had
      onset of DM1 during the winter months and the lowest frequency occurred in summer
      (p<0.005). The duration of breast-feeding, introduction time of cow's milk, and
      seasonal distribution of birth-month or onset of disease did not significantly
      differ in both groups. When compared with patients who had no documented
      honeymoon period, the patients who had a documented honeymoon period had lower
      HbA1c levels (p<0.01) at the onset. A large percentage of patients with DM 1A
      were positive for glutamic acid decarboxylase antibody (GAD65). CONCLUSION: There
      was no significant difference between patients with DM 1A and DM 1B with respect
      to epidemiologic features, and clinical presentation suggested that these factors
      do not play a major role either in creating a disease-initiating effect or in the
      development of islet autoimmunity. However, determination of GAD65 with HbA1c
      levels at the onset of the disease may ensure some useful information regarding
      clinical course.

PMID- 17457483
TI  - Incidence of ectopic pregnancy after assisted reproduction treatment.
AB  - OBJECTIVE: To assess the ectopic pregnancy risk among women who conceived with
      assisted reproductive technology (ART) procedures. METHODS: We performed a
      retrospective analysis of pregnancies as a result of ART procedure at McGill
      University Health Center, Quebec, Canada for the period from 1997 to 2006.
      RESULTS: The ectopic pregnancy rate was 1.6% and the heterotopic pregnancy rate
      was 13%. Maternal age, number of embryos transferred, ovarian hyperstimulation
      syndrome, use of assisted hatching, and Intra Cytoplasmic Sperm Injection (ICSI)
      were not significant predictors of ectopic pregnancy. CONCLUSION: Ectopic
      pregnancy rate in ART pregnancies is comparable to that of spontaneous
      pregnancies.

PMID- 17457484
TI  - An incidence study on thyroglossal duct cysts in adults.
AB  - OBJECTIVE: To investigate the incidence of the asymptomatic thyroglossal duct
      anomalies and to review the literature and make comments on the significance of
      this condition. METHODS: A total of 80 cadavers were dissected in the present
      study. This study was carried out during 2005, where the cadavers were randomly
      included from the criminal laboratories of the Ministry of Justice, Republic of
      Turkey in Istanbul. None of the cadavers had laryngeal and cervical injuries
      resulting from a trauma or the cause of their death. The examined cadavers
      included 59 men and 21 females, and their age were ranged from 35-80 years old.
      The larynges were removed and fixed in 10% formalin and then dissected. The
      sections were examined using surgical SMZ 10 Nikon stereomicroscope. We evaluated
      the presence, localization, and diameter of the cysts with regard to age and sex
      of the cadavers. RESULTS: We observed a total of 12 different localization of
      thyroglossal ducts and cysts among the dissected 80 cadavers. Ten of these ducts
      cysts were found in males with an age range of 35-68 years and 2 in female
      cadavers aged 46-65 years. In 6 cases, the thyroglossal ducts and cysts were
      located in the left of the midline of the neck, while 3 cases were from the right
      of the midline, and the remaining was located on the midline of the neck. In all
      cases, thyroglossal ducts and cysts were complete and restricted to the
      infrahyoid region; all of them had connection with the hyoid bone, but not with
      the perichondrium of the cartilage. In addition, the thyroglossal ducts had
      connection with the left lobe of the thyroid glands in 3 cases, one case in the
      right lobe, and 2 cases with the isthmus of the thyroid gland. Finally, in 5
      cases thyroglossal ducts were complete and had well-developed cysts. CONCLUSION:
      Thyroglossal duct remnants are one of the most often seen congenital asymptomatic
      masses of the neck region (7%). The presence of these duct remnants may lead to
      abnormal phonation and epithelial carcinomas. Therefore, correlation of the rate
      of thyroglossal duct remnants in a population together with the related clinical
      symptoms can lead to an early diagnosis and better treatment chances for these
      problems.

PMID- 17457485
TI  - Quality of life following endoscopic resection or radio-therapy for early glottic
      cancer.
AB  - OBJECTIVE: To compare post treatment quality of life (QoL) of patients treated by
      radiotherapy or endoscopic transoral endolaryngeal surgery using two quality of
      life scoring tools. METHODS: From May 1998 to July 2005, 48 patients (11 women
      and 37 men) with early glottic cancer were treated with curative radiotherapy (18
      patients) or laser cordectomy (30 patients), and retrospectively evaluated using
      QoL questionnaires; European Organization for Research and Treatment of Cancer
      (EORTC) - EORTC-QoL Core Questionnaire (QLQ-C30 version 2.0) and organ specific
      EORTC - QLQ, Head and Neck Module (QLQ-H&N35) at the University Hospital Motol,
      Czech Republic. RESULTS: Mean follow-up was 24 months. Only patients in complete
      remission were enrolled in the study. The overall score calculated separately for
      both questionnaires was not statistically different between both groups.
      Statistically significant differences were found only in specific group of
      questions focusing on saliva production (p=0.034) and sexuality performance
      (p=0.002). The majority of cases treated with cordectomy were Tis lesions. In the
      radiotherapy group, T1 lesions predominated (p=0.0001). Patients treated with
      radiotherapy were significantly older than those treated with cordectomy
      (p=0.027), which could explain the worsened score in sexuality questions. There
      were no significant differences found between genders allocated either to
      cordectomy or radiotherapy group. CONCLUSION: The overall QoL did not differ
      between patients treated with cordectomy or radiotherapy, despite the fact that
      patients treated with radiotherapy had more advanced disease and were older.
      There was significantly worse saliva and sexuality question score in the
      radiotherapy group.

PMID- 17457486
TI  - Percutaneous K-wiring for Gartland type III supracondylar humerus fractures in
      children.
AB  - OBJECTIVE: To assess the ability of closed reduction and percutaneous K-wire
      fixation, to obtain and maintain an adequate reduction, and thereby achieve
      satisfactory end results. METHODS: A prospective study conducted on 60 children
      over 28 months at Jawaharlal Nehru Medical College, Aligarh Muslim University,
      Aligarh, India, from March 2003 to June 2005, in which Gartland type-III
      supracondylar fracture humerus were treated by closed reduction and percutaneous
      pinning, either from lateral side only or from medial side also, under image
      intensifier control. RESULTS: There was no problem in union. Patients were graded
      by Flynn's criteria with excellent results in 88.88%, good in 4.44%, and fair in
      2.24%, and poor in 4.44% cases. Only one patient had developed cubitus varus
      deformity and one had Iatrogenic Ulnar nerve palsy from medial pin, which
      recovered subsequently. The Baumann's angle was well with in the normal range of
      66-84 degrees [corrected] CONCLUSION: Percutaneous K-wire fixation is a safe and
      effective method for the management of Gartland type-III supracondylar fractures
      with minimal hospital stay and without risking vascular compromise.

PMID- 17457487
TI  - A simple method for percutaneous resection of osteoid osteoma.
AB  - OBJECTIVE: To introduce a method that can be performed with minimal equipments
      available to most orthopedic surgeons and precludes the extensive anesthetic and
      ablative requirements. METHODS: A percutaneous lead tunnel was first established
      in the cortex next to the nidus under computerized tomography guidance with local
      anesthesia; then the nidus was curetted in the operating room through the lead
      tunnel. The study was performed in Shariati Hospital in Tehran, Iran, from
      September 2002 to December 2005. RESULTS: Nineteen patients were treated with
      this method with 94.7% cure rate. The diagnosis was histologically confirmed in
      16 cases (84.2%). Failure occurred in one patient. The patients had a mean follow
      up of 13.5 months with no recurrence of symptoms with mean hospitalization time
      of 1.6 days. CONCLUSION: This technique is simple, minimally invasive and
      effective. It needs no especial equipments and provides the material for tissue
      diagnosis.

PMID- 17457488
TI  - The effect of nonsteroidal anti-inflammatory drugs on rat gastric mucosa. The
      role of endothelin.
AB  - OBJECTIVE: To investigate the role of endothelin on nonsteroidal anti
      inflammatory drugs (NSAIDs) and selective cyclooxygenase-2 (COX2) enzyme
      inhibitors-induced effects on the gastric mucosa. METHODS: This study was carried
      out in the Department of Pharmacology Laboratory, Faculty of Medicine, Dokuz
      Eylul University, Izmir, Turkey during the period January to December 2002. In
      the first group a cyclooxygenase-1 (COX1) and COX2 enzyme inhibitor, indomethacin
      (25 mg/kg, subcutaneous injection (s.c), n=7), a selective COX2 enzyme inhibitor,
      NS398 (10 mg/kg, s.c) and normal saline were administered. In the second group,
      endothelin-1 (ET1) was administered (200 pmol/kg) alone, in the presence of an
      endothelin receptor antagonist bosentan, (100 mg/kg) and PGE1 [40 microg/kg,
      orally] with submucosal injection. In the third group, NS398 and indomethacin
      were applied in the presence of bosentan. In the fourth group, NS398 were applied
      in the presence of N (G)-nitro-l-arginine methyl ester (L-NAME) (10 mg/kg, s.c).
      RESULTS: Indomethacin caused gastric mucosal injury. The effect of NS398 on
      gastric mucosa did not differ considerably from that of the control group.
      Submucosal injection of ET1 caused a gastric damage, which could not be prevented
      by intragastric administration of bosentan, while pretreatment with PGE1
      prevented ET1-induced ulcer. Pretreatment with bosentan did not attenuate
      indomethacin-induced gastric mucosal damage but it increased NS398-induced damage
      by 1.5 fold. Pretreatment with L-NAME increased NS398-induced gastric mucosal
      damage as bosentan did. CONCLUSION: These results suggest that neither endothelin
      induced nor indomethacin-induced ulcer is completely receptor dependent.
      Cyclooxygenase-2 inhibitors caused ulcer in the presence of bosentan. Protective
      effects of gastric mucosal injury of COX2 inhibitors may be via endothelin
      receptor related nitric oxide release.

PMID- 17457489
TI  - Evaluation of drug and poison information center in Saudi Arabia during the
      period 2000-2002.
AB  - OBJECTIVE: To evaluate the profile of the requestors, the number and content of
      questions which were received during the period of May 2000 - December 2002.
      METHODS: A total of 1967 requests were evaluated. The questions were sorted
      according to source of callers, caller identification, the content of the
      questions, search data and time required to answer the questions. All data
      analysis were performed using the Statistical Package for Social Sciences Version
      9.0. RESULTS: The questions were received from different places, including Riyadh
      (90.1%), overall the Kingdom (8.9%) and gulf countries (1%). The Drug and Poison
      Information Center (DPIC) provides information to pharmacists, community,
      employee of King Saud University, physicians, nurses, dentists and others. The
      type of requests most frequently inquired about were drug related, health
      related, article/information, and poisoning. Requested data include information
      about therapeutics uses, drug identification, articles, adverse effects,
      dosage/administration, drug interactions, poisoning, with very few questions
      about availability, pregnancy and lactation, and IV incompatibilities. The most
      common resources used were Drugdex and internet, reference books, Iowa Drug
      Information Services (IDIS), PubMed and Poisondex. The time devoted to the
      service is varied ranging from 5 minutes to weeks. CONCLUSION: This study
      emphasizes on how important to document type of the activities of the DPIC to be
      used as a vital quality assurance tool. It also revealed the need to stimulate
      more requestors particularly physicians by advertising the drug information
      activities or possibly by establishing a website for the DPIC.

PMID- 17457490
TI  - Hypoplastic left heart syndrome and valvular pulmonary stenosis. A rare
      association that limits the management options.
AB  - A term baby had cyanosis 2 hours after delivery; echocardiography showed
      hypoplastic left heart syndrome HLHS and valvular pulmonary stenosis PS. The
      opinions of the cardiac centers in Saudi Arabia were taken; however, the baby was
      not accepted probably because the associated PS made him a poor candidate for a
      Norwood procedure and because cardiac transplant is not available for infants in
      Saudi Arabia. He died after 15 days. This mother should have fetal
      echocardiography in future pregnancies, and if HLHS is suspected she might be
      advised to seek medical advice antenatally at highly specialized cardiac centers
      abroad, as delivery there may increase the chance of surgical intervention.

PMID- 17457491
TI  - Inflammatory myofibroblastic tumor of paranasal sinuses.
AB  - Inflammatory myofibroblastic tumors IMTs are clinico-pathologically distinctive
      but biologically controversial entities; they rarely affect the head and neck
      region and usually follow a benign clinical course after radical excision. We
      reviewed the literatures of IMTs and present a rare case of IMT arising from the
      maxillary paranasal sinus of an 11-year-old girl. Moreover, we elaborate on the
      morpho-immunophenotypic characteristics of this lesion. Microscopic examination
      revealed a spindle cell proliferation set in a highly vascular stroma with
      numerous inflammatory cells. Tumor cells were immunoreactive for vimentin, and
      smooth muscle actin, negative for desmin, S-100, p53, Cyclin D1, and bcl-2. The
      potential neoplastic nature of this lesion was substantiated by the strong
      diffuse immuno-expression of ALK-1 protein, a marker that has been linked to
      neoplastic transformation. The lesion was excised completely by a CO2 LASER as a
      new treatment modality and the patient manifested no evidence of disease
      recurrence at 10-months recall.

PMID- 17457492
TI  - Familial hypercholesterolemia.
AB  - Familial homozygous hypercholesterolemia is a rare autosomal disorder
      characterized by high levels of cholesterol, extensive tendon xanthomatosis and
      premature development of atherosclerotic disease. Early coronary artery disease
      with myocardial infarctions and sudden deaths are common. We reported a family of
      familial hypercholesterolemia from the Kashmir valley of the Indian subcontinent.
      The appearance and the severity of the cutaneous xanthomas was found to be age
      related suggesting a role for the duration of hypercholesterolemia in the
      development of xanthomatosis.

PMID- 17457493
TI  - Small bowel perforation due to metastatic lung squamous cell carcinoma.
AB  - Squamous cell cancer of the lung occurs with early dissemination but clinically
      significant metastases localized to the small bowel are rare. Small bowel
      metastasis is a fatal complication usually seen in advanced stages of the
      disease. In the present study, we report a case of a 65-year-old patient who was
      admitted to the emergency department with acute abdominal pain and during
      evaluation was found to have squamous cell carcinoma metastasis to small bowel
      leading to perforation. We also discuss the current management possibilities in
      the guidance of current literature.

PMID- 17457494
TI  - Aggressive primary thyroid non Hodgkin's lymphoma with pregnancy.
AB  - We present here a multigravida patient who presented with a huge neck swelling,
      severe respiratory distress together with dysphagia and hoarseness of voice while
      she was pregnant +/- 30 weeks of gestation. She was diagnosed as an aggressive
      non-Hodgkin lymphoma of the thyroid gland. She was treated by 6 cycles of
      chemotherapy, with dramatic response after receiving the first cycle. She had 3
      cycles of 4 chemotherapeutic agents before successful, elective and scheduled
      induction of labor at 36 weeks of gestation with favorable outcomes.

PMID- 17457495
TI  - Unusual mechanism of isolated torsion of fallopian tube following minor trauma.
      Herniation through a broad ligament tear.
AB  - Isolated torsion of the fallopian tube without ovarian involvement and associated
      pathology is a rare event. We report an 18-year-old single female who presented
      with acute lower abdominal pain during menstruation after a minor trauma of the
      pelvis. It was diagnosed as isolated torsion of normal right tube during
      laparatomy due to herniation of the tube through a tear in the broad ligament.

PMID- 17457496
TI  - Intestinal perforation from primary intra-abdominal fibromatosis.

PMID- 17457497
TI  - Apnea after reversal of neuromuscular blockade. A case of rare mix-up.

PMID- 17457498
TI  - Paeonol inhibits the proliferation of human colorectal carcinoma cells and
      synergic with chemotherapeutic agents.

PMID- 17457499
TI  - Household cardiovascular health education. A school-based approach.

PMID- 17457500
TI  - Changes of the immune status in pregnancies complicated by diabetes.

PMID- 17457501
TI  - A high rate of caesarean section at a newly opened university hospital.

PMID- 17457502
TI  - Loss of zonal organization of articular cartilage after experimental subchondral
      trauma of the knee joint.

PMID- 17457503
TI  - Beneficial effects of soy protein isoflavones on lipid and blood glucose
      concentrations in type 2 diabetic subjects.

PMID- 17457504
TI  - Gangrenous ecthyma in infancy.

PMID- 17457505
TI  - Dermatitis herpetiformis and rheumatoid arthritis.

PMID- 17457506
TI  - The pattern of fetal hemoglobin changes in patients with malignancy on
      chemotherapy.

PMID- 17457508
TI  - Single- and multi-component adsorption of Pb, Cu, and Cd on peat.

PMID- 17457509
TI  - Use of synthetic mesh in pelvic reconstructive surgery: a survey of attitudes and
      practice patterns of urogynecologists.
AB  - This study surveyed attitudes and practice patterns of urogynecologists regarding
      the use of synthetic mesh in pelvic reconstructive surgery. A web-based survey
      was administered to members of the American Urogynecologic Society. The survey
      evaluated the use of the mesh for sacrocolpopexy, suburethral sling, and vaginal
      pelvic reconstructive surgery. The survey had a 30.5% response rate. One hundred
      one (39%) respondents were women, and 158 (61%) were men. One hundred forty-seven
      (56.8%) participated in fellowship training. Two hundred forty-seven (99.5%)
      currently perform procedures using synthetic mesh, including 93% who perform
      sacrocolpopexy and 93% who perform suburethral slings. In a logistic regression
      model including gender, fellowship training, and practice setting, male surgeons
      and those who had not undergone fellowship training were more likely to use the
      mesh than those who were fellowship trained. Respondents use the mesh most
      commonly when performing sacrocolpopexies and suburethral slings. The use of the
      mesh for anterior and posterior colporrhaphy is less common.

PMID- 17457510
TI  - Neutralising antibodies to interferon beta in multiple sclerosis : expert panel
      report.
AB  - Interferon beta (IFNbeta) therapy for multiple sclerosis (MS) is associated with
      a potential for the development of neutralising antibodies (NAbs) that negatively
      affect therapy. Several factors influence the development of NAbs, such as lack
      of complete sequence homology with the endogenous IFNbeta sequence, frequency of
      administration, level of dose and formulation of IFNbeta. Taken together, the
      evidence that NAb status reduces clinical efficacy in MS patients is strong.
      Standardised assays for NAbs are lacking, and titres vary over time. NAb testing
      is a critical component of care for MS patients because it provides information
      on one of the most important factors determining clinical responsiveness to
      IFNbeta therapy. This expert panel report attempts to move the field towards
      resolution of the remaining issues and considers several aspects of NAbs,
      including their clinical relevance, factors influencing immunogenicity, assays to
      quantify NAbs and the definition of clinically relevant titres.

PMID- 17457511
TI  - From low to high: late-onset intracranial hypertension after treatment of
      spontaneous intracranial hypotension.

PMID- 17457512
TI  - Genetic determination in onset age of wrist fracture.
AB  - The onset age of fracture may be useful to explore the clinical and genetic
      heterogeneity of fracture study. In the present study, we investigated the
      heritability of the onset age of wrist fracture (OAWF) in 30 female full-sib
      pairs. The phenotypic correlation coefficient of OAWF was 0.309 (P=0.09) for this
      cohort of female sib pairs, and the narrow-sense heritability (h2) was estimated
      to be 0.618 (P=0.09). In addition, the h2 derived from the variance component
      model implemented in SOLAR was 0.722 (P<0.05). This study, for the very first
      time, suggested that OAWF is under genetic control and thus potentially helps
      clarify genetic heterogeneity of wrist fracture.

PMID- 17457513
TI  - Historical controls for phase II surgically based trials requiring gross total
      resection of glioblastoma multiforme.
AB  - New treatments for patients with glioblastoma multiforme (GBM) are frequently
      tested in phase II surgically based clinical trials that require gross total
      resection (GTR). In order to determine efficacy in such single-arm phase II
      clinical trials, the results are often compared to those from a historical
      control group that is not limited to patients with GTR. Recursive partitioning
      analysis (RPA) can define risk groups within historical control groups; however,
      RPA analyses to date included patients irrespective of whether a patient had a
      GTR or not. To provide a more appropriate historical control group for surgically
      based trials requiring a GTR, we sought to determine survival for a group of
      patients with newly diagnosed GBM, all of who underwent GTR and were treated on
      prospective clinical trials. GTR was defined as removal of >90% of the enhancing
      mass, determined by postoperative magnetic resonance imaging. Of 893 patients
      with GBM treated during these trials, 153 underwent GTR. The median survival for
      the GTR group was 71 weeks (95% CI 65-76) which was better than those who did not
      have a GTR. Within the GTR group, the median age was 54 years (range 25-77
      years), and median Karnofsky Performance Score was 90 (range 60-100). Considering
      only patients with GTR, age at diagnosis continued to be a statistically
      significant prognostic factor. Patients treated during surgically based phase II
      studies should be matched with a historical control group restricted to patients
      with similar pretreatment variables, including GTR.

PMID- 17457514
TI  - Evidence for direct interactions between the mercuric ion transporter (MerT) and
      mercuric reductase (MerA) from the Tn501 mer operon.
AB  - Mercuric ion resistance in bacteria requires transport of mercuric ions (Hg(2+))
      into the cytoplasmic compartment where they are reduced to the less toxic
      metallic mercury (Hg(0)) by mercuric reductase (MR). The long-established model
      for the resistance mechanism predicts interactions between the inner membrane
      mercuric ion transporter, MerT, and the N-terminal domain of cytoplasmic MR, but
      attempts to demonstrate this interaction have thus far been unsuccessful. A
      recently developed bacterial two-hybrid protein interaction detection system was
      used to show that the N-terminal region of MR interacts with the cytoplasmic face
      of MerT. We also show that the cysteine residues on the cytoplasmic face of the
      MerT protein are required for maximal mercuric ion transport but not for the
      interaction with mercuric reductase.

PMID- 17457515
TI  - Indocyanine green angiography in Vogt-Koyanagi-Harada disease: angiographic signs
      and utility in patient follow-up.
AB  - PURPOSE: Firstly, to give a review of characteristic indocyanine green
      angiographic (ICGA) signs in Vogt-Koyanagi-Harada (VKH) disease and, secondly, to
      determine the utility of ICG angiography in the assessment and follow-up of
      choroidal inflammatory activity during initial high-dose inflammation suppressive
      therapy and during the tapering of therapy. METHODS: We have first reviewed
      characteristic ICGA signs in VKH. This is followed by a study of four patients
      with an acute initial VKH uveitis episode who received regular initial and follow
      up angiographic examinations for at least 9 months. Classical ICGA signs were
      recorded at onset and followed for at least 9 months and were correlated with
      treatment levels. The treatment consisted of high-dose oral corticosteroids (0.8
      1.5 mg/kg) preceded by pulse intravenous methylprednisolone (500-1000 mg) for 3
      days in hyperacute cases and followed by very slow tapering with the addition of
      an immunosuppressive agent in cases of insufficient response. RESULTS: The major
      ICGA signs that were both consistently present and easy to record in the four VKH
      patients having an acute initial uveitis episode with a pre-treatment angiography
      and an angiographic follow-up for a minimum of 9 months include (1) early
      choroidal stromal vessel hyperfluorescence and leakage, (2) hypofluorescent dark
      dots, (3) fuzzy vascular pattern of large stromal vessels and (4) disc
      hyperfluorescence. All patients were treated with high-dose inflammation
      suppressive therapy: in two patients, within 14 and 21 days after initial
      symptoms, respectively, and in the other two patients, within 6 weeks.
      Hypofluorescent dark dots, the most constant and easily recordable sign, was very
      prominent in all cases at presentation. A 90% to complete resolution of dark dots
      was noted in all four patients after 4 months of therapy. The other three major
      angiographic signs, early choroidal stromal vessel hyperfluorescence and leakage,
      indistinct fuzzy vessels at the intermediate angiographic phase and disc
      hyperfluorescence resolved in all cases within 8 weeks or less of high-dose
      inflammation suppressive therapy. In three of the four patients, dark dots
      reappeared after a mean of 7.8 +/- 2.8 months after onset of therapy when the
      patients were under a mean corticosteroid dose of 13.2 +/- 6.3 mg per day without
      any significant clinical or fluorescein angiographic signs, indicating
      subclinical recurrence. An increase in the inflammation suppressive therapy again
      brought about angiographic resolution of choroidal subclinical disease in all
      cases. CONCLUSION: Choroidal inflammation shown by ICG angiography can be
      suppressed completely by initial high-dose inflammation suppressive therapy.
      However, recurrent subclinical choroidal inflammation is detected at the end of
      the tapering period in a high proportion of cases. This indicates that, in the
      absence of an ICGA follow-up, undetected smoldering subclinical disease may
      persist, thereby explaining the frequently reported evolution towards sunset glow
      fundus despite an apparently controlled disease. This is a clear indication that
      VKH disease should be followed by ICG angiography and, in the case of choroidal
      subclinical reactivation, a reversal of therapy tapering and an extension of
      therapy duration should be considered.

PMID- 17457516
TI  - A new model for chemical shifts of amide hydrogens in proteins.
AB  - We propose a new computational model to predict amide proton chemical shifts in
      proteins. In addition to the ring-current, susceptibility and electrostatic
      effects of earlier models, we add a hydrogen-bonding term based on density
      functional calculations of model peptide-peptide and peptide-water systems. Both
      distance and angular terms are included, and the results are rationalized in
      terms of natural bond orbital analysis of the interactions. Comparison to
      observed shifts for 15 proteins shows a significant improvement over existing
      structure-shift correlations. These additions are incorporated in a new version
      of the SHIFTS program.

PMID- 17457517
TI  - Fiber specific differential phosphorylation of the alpha1-subunit of the Na(+),K
      (+)-ATPase in rat skeletal muscle: the effect of aging.
AB  - In skeletal muscle, the Na(+),K(+)-ATPase maintains the Na(+) and K(+) gradients
      and modulates contractile functions. The different fibers of the skeletal muscle
      possess diverse properties and functions, and thus, the demands for the Na-pump
      activity might be different. Because phosphorylation of the alpha1-subunit of the
      Na(+),K(+)-ATPase appears to serve a regulatory role in the activity of
      Na(+),K(+)-ATPase, we postulated that a difference in the phosphorylation of the
      alpha1-subunit may be found among the fibers. We utilized two well-characterized
      specific antibodies for the alpha1-subunit, namely the McK1 and alpha6F, to
      determine, by immunofluorescence, if the alpha1-subunit in rat skeletal muscle
      fiber is differentially phosphorylated. McK1 has the unique property that its
      binding to the alpha1-subunit is greatly reduced when Ser-18 is phosphorylated.
      Our data show that, in red gastrocnemius muscle, only a small number of the
      fibers were stained on the sarcolemmal membrane by McK1, while other fibers were
      almost completely devoid of any staining. By contrast, the staining pattern by
      McK1 in the white gastrocnemius muscle was mostly uniform. Immunostaining of
      serial sections using the alpha6F antibody showed that the alpha1-subunit is
      expressed in all fibers. Dephosphorylation of the tissue sections by phosphatase
      partially restored immunostaining of the alpha1-subunit by McK1. Fiber typing
      results showed that, in red gastrocnemius, those fibers stained positive for
      alpha1-subunit by McK1 are the Type I fibers, whereas those stained negative are
      the Type IIA, IID, and IIB fibers. With age, the number of fibers in red
      gastrocnemius stained positive for McK1 increased markedly in 30-month old rats
      compared to 6-month old rats. In conclusion, our result suggests that, in rats,
      the alpha1-subunit of the Na(+),K(+)-ATPase is differentially phosphorylated in
      the fibers of the red gastrocnemius muscle. Furthermore, advanced age is
      associated with an apparent decrease in the phosphorylation of the alpha1
      subunit, in addition to the previously demonstrated increase in the levels of
      expression of the subunit.

PMID- 17457518
TI  - Regulation of nucleo-cytoplasmic shuttling of human annexin A2: a proposed
      mechanism.
AB  - Studies have long been focused on the functions of annexin A2 in the cytoplasm.
      However, the involvement of annexin A2 in DNA replication as a part of primer
      recognition protein complex and the presence of nuclear export signal (NES)
      suggest that annexin A2 is also functional in the nucleus, and its localization
      in the nucleus is under regulation by interaction with other nuclear factors
      through its N-terminus. During the study of the mechanism of annexin A2
      sequestering in the nucleus and the regulation of its export from the nucleus, in
      this study, we show that endogenous annexin A2 is present in both the cytoplasm
      and the nucleus in HeLa, PC-3 and DU-145 cells. While exogenously expressed
      annexin A2 is excluded from nuclei of annexin A2-null LNCaP cells in a CRM1
      (Chromosome Maintenance Region 1) mediated nuclear export, endogenous annexin A2
      in HeLa, PC-3 and DU-145 cell lines does not undergo the CRM1 mediated nuclear
      export. While investigating the mechanism of the nuclear retention of annexin A2,
      we found that an anti-annexin A2 antibody that recognizes the C-terminus of
      annexin A2 (D1/274.5) cannot recognize nuclear annexin A2, suggesting that the
      domain recognized by this antibody may be masked in the nuclei. In order to find
      out the role of annexin A2 C-terminus in the nuclear retention of annexin A2, we
      transiently transfected green fluorescence protein (GFP)-fused N-terminal 29
      amino acids of annexin A2 to LNCaP, PC-3 and DU-145 cells, and determined that
      the C-terminus is not required for the nuclear retention of annexin A2. Based on
      the finding described above, we propose a model for nuclear retention of annexin
      A2 where the regulation sites reside in the N-terminus and are adjacent to the
      NES, and upon modification, the NES is exposed and annexin A2 is exported from
      the nucleus.

PMID- 17457519
TI  - Expression and transcriptional activity of alternative splice variants of Mitf
      exon 6.
AB  - Microphthalmia-associated transcription factor (Mitf) is a tissue-specific
      transcription factor. At least nine distinct mouse isoform mRNAs are encoded by
      alternative splicing of the first exon of Mitf (Mitf-A, -B, -C, -D, -E, -H, -J, 
      M, and -mc), while exons 2-9 of all Mitf isoforms examined to date are identical.
      In addition, alternative splice variants of exon 6a encoding 6 amino acid
      proximal to the basic region of the protein are known in Mitf-A, -H, and -M. In
      this study, we identified alternative splice variants of exon 6a in other Mitf
      isoforms (Mitf-E, -J, and -mc) in melanocytes, mast cells, macrophages, and
      heart. We also compared the transcriptional activity of Mitf variants containing
      exon 6a to that of Mitf variants that did not contain exon 6a. PCR-RFLP analysis
      revealed that expression of Mitf with exon 6a was comparable with that of Mitf
      without exon 6a, irrespective of the specificity of the first exon, or cell type,
      although Mitf isoforms with different first exons were expressed in a cell type
      dependent manner. Luciferase-based reporter assays revealed that transcription of
      Tyrosinase, which is known Mitf-regulated gene, was elicited more efficiently by
      expression of Mitf isoforms containing exon 6a, compared to isoforms that did not
      contain exon 6a. However, when transcription of Tyrp-1, Mmcp-6, and PAI-1 was
      examined, no significant differences were detected between Mitf isoforms with
      exon 6a and those without exon 6a, except for Tyrp-1 transcription by Mitf-D/E
      isoform. These results reveal a diverse pattern of gene expression and different
      transcriptional activities of Mitf isoforms, suggesting discrete regulation of
      gene transcription in specific tissues by Mitf.

PMID- 17457520
TI  - Western array analysis of cell cycle protein changes during the hyperplastic to
      hypertrophic transition in heart development.
AB  - Cardiac myocytes proliferate most rapidly during the hyperplastic phase of heart
      development; however, the level of cell cycle activity is drastically down
      regulated after birth. Further growth of the heart is achieved by hypertrophic
      growth of cardiac myocytes. The mechanism that controls the switch from
      hyperplastic proliferation to hypertrophic growth in cardiac myocytes is unknown.
      Understanding this fundamental mechanism of cardiac myocyte biology would be most
      beneficial for studies directed towards myocardial regeneration. In this study,
      we identified changes in the expression of proteins involved in cell cycle
      regulation during the hyperplastic to hypertrophic transition of cardiac
      myocytes. Using a high-throughput immunoblotting technique, we examined 200+
      proteins in primary cultures of cardiac myocytes at different developmental time
      points to determine the important regulators of this transition. In addition, we
      also analyzed samples from an immortalized cardiac myocyte cell line to compare
      expression levels of cell cycle regulatory proteins to our primary cultures. Our
      findings by this uncovered proteomic screen identified several potential key
      regulatory proteins and provide insight into the important components of cardiac
      myocyte cell cycle regulation.

PMID- 17457521
TI  - Oxidative stress enhances phosphorylation of p53 in neonatal rat cardiomyocytes.
AB  - p53 is an important regulator of cell growth and apoptosis and its activity is
      regulated by phosphorylation. Accordingly, in neonatal rat cardiomyocytes we
      examined the involvement of p53 in H(2)O(2)-induced apoptosis. Treatment with 50
      100 microM H(2)O(2) markedly induced apoptosis in cardiomyocytes, as assessed by
      gel electrophoresis of genomic DNA. To examine whether H(2)O(2) increases p53
      phosphorylation in cardiomyocytes, we utilized an antibody that specifically
      recognizes phosphorylated p53 at serine-15. The level of phosphorylated p53 was
      markedly increased by 100 microM H(2)O(2) at 30 and 60 min. Using specific
      protein kinase inhibitors we examined the involvement of protein kinases in p53
      phosphorylation in response to H(2)O(2) treatment. However, staurosporine, a
      broad spectrum inhibitor of protein kinases, SB202190, a specific p38 kinase
      inhibitor, PD98059, a MAP kinase inhibitor, wortmannin, an inhibitor of DNA-PK
      and PI3 kinase, SP600125, a JNK inhibitor and caffeine,an inhibitor of ATM and
      ATR, failed to prevent the H(2)O(2)-induced phosphorylation of p53. cDNA
      microarray revealed that H(2)O(2) markedly increased expression of several p53
      upstream modifiers such as the p300 coactivator protein and several downstream
      effectors such as gadd45, but decreased the expression of MDM2, a negative
      regulator of p53. Our results suggest that phosphorylation of p53 at serine-15
      may be an important signaling event in the H(2)O(2)-mediated apoptotic process.

PMID- 17457522
TI  - Antioxidant effect of the marine algae Chlorella vulgaris against naphthalene
      induced oxidative stress in the albino rats.
AB  - Alcoholic extract of the marine algae Chlorella vulgaris was examined for its
      free radical scavenging effect with reference to naphthalene-induced lipid
      peroxidation in serum, liver, and kidney of rats. Initially, upon naphthalene
      intoxication (435 mg/kg body weight, intraperitoneally), the lipid peroxidation
      activity increased significantly (P < 0.001), and in contrast, the enzymic
      antioxidants (superoxide dismutase, catalase, glutathione peroxidase) and non
      enzymic antioxidants (glutathione, ascorbic acid, and alpha-tocopherol) levels
      decreased remarkably. When the naphthalene stressed rats were treated with
      Chlorella vulgaris extract (70 mg/kg body weight, orally), the lipid peroxidation
      activity reduced significantly (P < 0.001) and the activities of both the enzymic
      and non-enzymic antioxidants increased reaching near control values. The minimum
      concentration (70 mg/l) of the extract that exhibited maximum (85%) free radical
      scavenging activity was chosen for the experimental study. The present results
      suggest that Chlorella vulgaris extract exerts its chemo-preventive effect by
      modulating the antioxidants status and lipid peroxidation during naphthalene
      intoxication.

PMID- 17457523
TI  - Stilbene derivatives inhibit the activity of the inner mitochondrial membrane
      chloride channels.
AB  - Ion channels selective for chloride ions are present in all biological membranes,
      where they regulate the cell volume or membrane potential. Various chloride
      channels from mitochondrial membranes have been described in recent years. The
      aim of our study was to characterize the effect of stilbene derivatives on single
      chloride channel activity in the inner mitochondrial membrane. The measurements
      were performed after the reconstitution into a planar lipid bilayer of the inner
      mitochondrial membranes from rat skeletal muscle (SMM), rat brain (BM) and heart
      (HM) mitochondria. After incorporation in a symmetric 450/450 mM KCl solution
      (cis/trans), the chloride channels were recorded with a mean conductance of 155
      +/- 5 pS (rat skeletal muscle) and 120 +/- 16 pS (rat brain). The conductances of
      the chloride channels from the rat heart mitochondria in 250/50 mM KCl
      (cis/trans) gradient solutions were within the 70-130 pS range. The chloride
      channels were inhibited by these two stilbene derivatives: 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4'
      isothiocyanostilbene-2,2'-disulfonic acid (SITS). The skeletal muscle
      mitochondrial chloride channel was blocked after the addition of 1 mM DIDS or
      SITS, whereas the brain mitochondrial channel was blocked by 300 microM DIDS or
      SITS. The chloride channel from the rat heart mitochondria was inhibited by 50
      100 microM DIDS. The inhibitory effect of DIDS was irreversible. Our results
      confirm the presence of chloride channels sensitive to stilbene derivatives in
      the inner mitochondrial membrane from rat skeletal muscle, brain and heart cells.

PMID- 17457524
TI  - The effect of TGF-beta1 and Smad7 gene transfer on the phenotypic changes of rat
      alveolar epithelial cells.
AB  - The aim of this study was to investigate whether transforming growth factor-beta1
      (TGF-beta1) could induce alveolar epithelial-mesenchymal transition (EMT) in
      vitro, and whether Smad7 gene transfer could block this transition. We also aimed
      to elucidate the possible mechanisms of these processes. The Smad7 gene was
      transfected to the rat type II alveolar epithelial cell line (RLE-6TN).
      Expression of the EMT-associated markers was assayed by Western Blot and Real
      time PCR. Morphological alterations were examined via phase-contrast microscope
      and fluorescence microscope, while ultrastructural changes were examined via
      electron microscope. TGF-beta1 treatment induced a fibrotic phenotype of RLE-6TN
      with increased expression of fibronectin (FN), alpha-smooth muscle actin (alpha
      SMA) and vimentin, and decreased expression of E-cadherin (E-cad) and
      cytokeratin19 (CK19). After transfecting the RLE-6TN with the Smad7 gene, the
      expression of the mesenchymal markers was downregulated while that of the
      epithelial markers was upregulated. TGF-beta1 treatment for 48 h resulted in the
      separation of RLE-6TN from one another and a change into elongated, myofibroblast
      like cells. After the RLE-6TN had been transfected with the Smad7 gene, TGF-beta1
      treatment had no effect on the morphology of the RLE-6TN. TGF-beta1 treatment for
      48 h resulted in an abundant expression of alpha-SMA in the RLE-6TN. If the RLE
      6TN were transfected with the Smad7 gene, TGF-beta1 treatment for 48 h could only
      induce a low level of alpha-SMA expression. Furthermore, TGF-beta1 treatment for
      12 h resulted in the degeneration and swelling of the osmiophilic multilamellar
      bodies, which were the markers of type II alveolar epithelial cells. TGF-beta1
      can induce alveolar epithelial-mesenchymal transition in vitro, which is
      dependent on the Smads signaling pathway to a certain extent. Overexpression of
      the Smad7 gene can partially block this process.

PMID- 17457525
TI  - Characteristics of the responses of visual cortex neurons with sensitivity to
      bars or cross-shaped figures in cats.
AB  - The magnitudes and latent periods of spike responses were recorded from 280
      individual neurons tuned to the orientation of light bars or cross-shaped figures
      in the primary visual cortex (field 17) of the cat. In control experimental
      conditions, half of 195 cells preferred the bar (first group), the remainder
      preferring crosses (second group); the responses of neurons of the first group to
      bars and crosses were of similar magnitude, while in the second group, responses
      to crosses were significantly larger than responses to bars. The latent periods
      of responses to optimal bars in the first group of neurons were shorter than
      those in the second group, and became longer on exposure to crosses, while latent
      periods in the second group were shorter on exposure to crosses. In conditions of
      local bicuculline blockade of intracortical inhibition, about a quarter of 85
      neurons were sensitive only to the bar, regardless of the presence or absence of
      inhibition. The remaining neurons were sensitive to crosses in at least one of
      the states and continued to have responses which were smaller in terms of
      absolute magnitude than the responses of group 1 neurons. The significance of
      these data for understanding the mechanisms of tuning of striate neurons to
      signal features and the temporal sequence of their operation is discussed.

PMID- 17457526
TI  - Significance of the context of cognitive activity in the formation of unconscious
      visual sets.
AB  - Experimental data from healthy humans on the context dependence of cognitive
      activity involved in the process of substituting a previously formed unconscious
      set with a new set appropriate to the altered conditions are discussed. The
      mobility/rigidity property of the visual set changes depending on the nature of
      the additional task introduced into the context (stimulus recognition or
      identification of the spatial position of a stimulus). It is hypothesized that
      the process of set substitution is facilitated when the context of cognitive
      activity includes alternation of the involvement of the ventral and dorsal visual
      systems in information processing.

PMID- 17457527
TI  - Characteristics of activation in the parietal areas of the cortex in humans in
      different types of visual attention.
AB  - The state of cortical activation in the parietal and temporal areas was assessed
      using evoked potentials (EP) during the tasks of selection of lateralized visual
      stimuli requiring three different types of attention: to stimulus shape, to
      stimulus position, and to both. Studies in 15 young, healthy subjects involved
      recording of EP in six cortical leads: P3, P4, T3, T4, T5, and T6, with analysis
      of the endogenous EP components CNV, N1, P3, and the EP complex [N1-P3]
      (according to standard terminology). Changes in EP components in response to the
      attended and non-attended stimulus features were compared. Differences between
      them were assessed using the index of selectivity of attention to one or another
      feature of the visual stimuli. In the parietal area, selectivity was seen in
      conditions of attention to stimulus position and attention to stimulus shape. In
      conditions of simultaneous attention, the indexes of selectivity were essentially
      equal to the sum of the indexes of selectivity of attention to shape and
      position. The most marked endogenous EP components (CNV, N1, and P3) in visual
      selection were seen in the parietal areas, with a greater gradient of increased
      activation of the parietal areas of the cortex as the need for attention
      increased, along with a lower threshold for the action of attention, and
      anticipatory development of the P3 wave in the parietal area as compared with the
      temporal area. These results suggest that the parietal cortex has priority in the
      visual attention system and that the magnocellular (M) pathway forms the most
      important visual input to the dorsal parietal area of the neocortex.

PMID- 17457528
TI  - Transcranial electrostimulation activates reparative regeneration and the insulin
      producing function of pancreatic B-cells in alloxan diabetes in rats.
AB  - Studies on rats with experimental diabetes induced by administration of alloxan
      showed that transcranial electrostimulation of endorphinergic brain structures
      stimulates the regeneration of damaged beta-cells in pancreatic islets of
      Langerhans. This was identified on pancreatic sections stained with hematoxylin
      and eosin. De novo formation of small islets was noted, as evidenced by their
      regeneration from progenitor cells. After transcranial electrostimulation, islet
      beta-cells stained by the Gomori method showed recovery of granularity - a sign
      of insulin production. Application of an immunoenzyme method demonstrated
      recovery of blood insulin levels, the dynamics of increases in which showed a
      highly significant negative correlation with a decrease in blood glucose. These
      data led to the conclusion that the antihyperglycemic effect of transcranial
      electrostimulation in experimental alloxan diabetes results from reparative
      regeneration of beta-cells in islets of Langerhans with recovery of their insulin
      producing function.

PMID- 17457529
TI  - Age-related characteristics of the neurotransmitter composition of neurons in the
      stellate ganglion.
AB  - The neurotransmitter composition of neurons in the stellate ganglion of rats of
      different ages (neonatal, 10, 20, 30, and 60 days) was studied by an
      immunocytochemical method using double labeling. Most neurons in rat pups of all
      age groups contained tyrosine hydroxylase. Most choline acetyltransferase
      positive neurocytes in neonatal and 10-day-old rat pups were also tyrosine
      hydroxylase-positive. Only occasional cells in 30-and 60-day rat pups contained
      both of these enzymes. There were increases in the proportions of cells
      containing tyrosine hydroxylase and neuropeptide Y from birth to all time points
      of the study. In addition, there was a decrease in the proportion of somatostatin
      positive neurons. The proportions of VIP-positive cells and choline
      acetyltransferase-containing neurons increased to age 10 days and then decreased.
      Somatostatin-positive neurons in all rat pups were small cells, while those
      containing choline acetyltransferase were large. Maturation of the
      neurotransmitter set in the rat stellate ganglion was complete by the end of the
      second month of life.

PMID- 17457530
TI  - Activation of the hypothalamo-hypophyseal-adrenocortical system as an important
      gastroprotective component of the stress reaction.
AB  - This article presents an analysis of data providing evidence of the important
      contribution of the hypothalamo-hypophyseal-adrenocortical system (HHACS) to the
      processes maintaining the integrity of the gastric mucosa. According to these
      data, glucocorticoid hormones produced during stress-induced activation of the
      HHACS are gastroprotective hormones rather than ulcerogenic factors, as is widely
      believed. The gastroprotective influence of glucocorticoids has been demonstrated
      on exposure to ulcerogenic stimuli of different modalities. The gastroprotective
      action of glucocorticoid hormones is mediated via type II glucocorticoid
      receptors and may be associated with the maintenance of the blood glucose level,
      their calming effects on pathogenetic factors, and their favorable effects on
      protective factors for the gastric mucosa. Glucocorticoid hormones can compensate
      for the absence of the gastroprotective action of prostaglandins, nitric oxide,
      and capsaicin-sensitive neurons. The data lead to the conclusion that activation
      of the HHACS is an important gastroprotective component of the stress reaction.

PMID- 17457531
TI  - The role of the hormones of the hypothalamo-hypophyseal-adrenocortical system in
      the analgesic effect of corticotropin-releasing hormone.
AB  - Experiments on anesthetized male rats were performed to study the role of the
      hormones of the hypothalamo-hypophyseal-adrenocortical system (HHACS) in
      analgesia induced by central or systemic administration of corticoliberin
      releasing hormone (CRF). Studies of the contribution of HHACS hormones were
      performed by blocking HHACS function by administration of hydrocortisone at a
      pharmacological dose one week before experiments started. Blockade of HHACS
      function, resulting in the inability of the system to increase hormone levels,
      resulted in a decrease in the analgesic effect resulting from systemic
      administration of CRF and completely abolished the analgesic effect after central
      administration of CRF. These data lead to the conclusion that there are two
      components involved in increasing the pain sensitivity threshold in response to
      administration of CRF: 1) a component dependent on HHACS hormones in central and
      systemic administration of CRF; 2) a component independent of HHACS hormones on
      systemic administration of CRF.

PMID- 17457532
TI  - The evoked potential as a measure of perceptual and semantic differences.
AB  - This review discusses the information content of perceptual and semantic evoked
      potentials arising in humans as a result of instantaneous changes in nonverbal
      and verbal stimuli. The amplitudes of perceptual and semantic evoked potentials
      were found to correlate positively with subjects' assessments of the differences
      between these stimuli. Multidimensional scaling matrixes of evoked potential
      amplitudes and subjective assessments of differences on pairwise substitution of
      stimuli showed that the actual colors and color names occupied a four-dimensional
      spherical color space and were encoded by excitation vectors of identical
      lengths. Color differences were equal to the absolute differences between their
      excitation vectors, while semantic differences in color names corresponded to the
      absolute difference vectors represented by long-term color memory traces. These
      data were reviewed in the framework of a spherical model of cognitive processes.

PMID- 17457533
TI  - Spectral EEG characteristics during increases in the complexity of the context of
      cognitive activity.
AB  - The spatial and frequency characteristics of cortical electrical activity were
      studied in healthy human subjects in two series of experiments involving solution
      of sequentially presented visual tasks. The first task was to assess the relative
      sizes of two circles and was identical in both series. In the first series, this
      was supplemented by a task consisting of recognition of pseudowords/words,
      presumptively also requiring predominant involvement of the ventral "what?"
      visual system. In the second series, the additional task (spatial localization of
      a target stimulus in a matrix of letters) was associated with the predominant
      involvement of the dorsal "where?" visual system. Cortical electrical activity
      immediately before presentation of pairs of tasks was analyzed. Measures of EEG
      spectral power in the frontal, central, occipital, and temporal areas of the
      cortex was subjected to dispersion analysis. The power of electrical potentials
      in the delta and beta1 frequency ranges was greater when both tasks were
      associated predominantly with activation of the ventral visual system (first
      series of experiments). Power in the occipital alpha rhythm was lesser in the
      left hemisphere in both series of experiments. The interaction of the
      "experimental series" and "hemisphere" factors was significant in the temporal
      areas for EEG activity in the alpha2 range, where the predominant involvement of
      the ventral visual system on solution of both tasks corresponded to greater
      asymmetry in the electrical oscillations in the rapid alpha2 rhythm and its
      neighboring beta1 range with greater desynchronization (lesser power) on the left
      side. Thus, the nature of the ongoing activity is reflected in the spatial
      frequency characteristics of the "background" electrical activity of the cortex.

PMID- 17457534
TI  - Comparative study of the gamma rhythm in normal conditions, during examination
      stress, and in patients with first depressive episode.
AB  - We report here a comparative analysis of measures of spectral power and
      synchronization of the gamma rhythm (30-40 Hz) in healthy subjects in normal
      conditions and before examinations (a stress situation) and in patients with
      major depression (first episode), both without cognitive loading and during
      performance of tests (arithmetic counting and spatial imagination). The results
      showed that the power of the gamma rhythm in the frontal and temporal areas of
      the cortex was significantly greater in patients with depression than in normal
      subjects. In the stress situation, healthy subjects showed a reduction in the
      number of differences in this measure as compared with depression patients, both
      at rest and during performance of the arithmetic counting test. the spatial
      imagination test resulted in a smaller number of significant differences between
      patients with depression and healthy subjects, regardless of whether the latter
      were in normal conditions or in the stress situation. The levels of gamma rhythm
      synchronization between cortical areas at rest and during cognitive loading were
      not different in healthy subjects, though synchronization increased in healthy
      subjects during stress and in patients with depression. Thus, the stress
      situation in healthy subjects leads to decreases in the differences in EEG
      measures from those in depression both at rest (power) and during cognitive
      loading (both measures). This may be evidence that stress is a "trigger
      mechanism" for depression.

PMID- 17457535
TI  - Encoding of stimulus movement parameters in the cat visual system.
AB  - Analysis of matrixes consisting of the numbers of spikes evoked by the movement
      of simple and complex stimuli in cat visual cortex neurons by the principal
      components method demonstrated vector encoding. The responses of direction
      detectors to the movement of points and orientation detectors to changes in the
      angle of a line were encoded independently in areas V1 and V2 of the cortex. Each
      type of detector was represented by excitation of two cardinal neurons generating
      sine and cosine functions. The responses of neurons in the associative cortex
      with selectivity for the direction of movement of specifically oriented bars
      depended on four cardinal neurons formed by summation of the excitations of the
      cardinal neurons of the directional and orientational channels.

PMID- 17457536
TI  - Theta driving both inhibits and potentiates the effects of nicotine on dentate
      gyrus responses.
AB  - The medial septal area of conscious rats was stimulated through previously
      implanted electrodes at a frequency of 7.7 Hz for 20 min each day for 7 days to
      evoke rhythmic slow activity in CA1 at a similar frequency to spontaneous theta.
      Two weeks later in the anaesthetized rats the effects of a single subcutaneous
      injection of nicotine (0.4 mg/kg) on fEPSPs, evoked in the dentate gyrus by
      separate stimulation of the MPP and LPP, were studied and compared with those
      obtained in controls. Nicotine increased the firing of locus coeruleus neurons
      and the slope of the fEPSPs evoked by LPP stimulation, but not by MPP
      stimulation. Prior theta driving considerably increased the effect of nicotine on
      the responses evoked by stimulation of the MPP and abolished the nicotine-induced
      potentiation of the responses evoked by stimulation of the LPP. The results are
      attributed to theta driving increasing the amount of noradrenaline released by
      nicotine and to noradrenaline producing a beta-adrenoceptor long-lasting
      potentiation at the medial perforant path synapse and a long-lasting depression
      at the lateral perforant path synapse.

PMID- 17457537
TI  - Involvement of protein synthesis in the reconsolidation of memory at different
      time points after formation of conditioned reflex freezing in mice.
AB  - The aim of the present work was to study the involvement of protein synthesis in
      the reconsolidation of memory at different periods of time after training. In
      mice trained in a conditioned reflex freezing model, memory was reactivated by a
      reminder combined with administration of the protein synthesis inhibitor
      cycloheximide. The results showed that suppression of protein synthesis on
      reactivation of memory 3, 6, and 24 h and 14 and 30 days after training impaired
      acquired conditioned reflex freezing. These data provide evidence that memories
      retrieved by a reminder require protein-dependent reorganization at both short (3
      6 h) and long (14-30 days) periods after training.

PMID- 17457538
TI  - Coaxil (tianeptine) in the treatment of depression in Parkinson's disease.
AB  - An open, non-comparative clinical study was performed to assess the efficacy and
      safety of tianeptine (Coaxil) in Parkinson's disease (PD). A total of 18 patients
      with PD were used whose clinical state increased moderately severe and more
      profound depression (assessed on the Hamilton and Beck scales). After three
      months of treatment, depression on the Hamilton depression scale was decreased by
      34% and on the Beck scale by 31% compared with baseline data ((p) < 0.05).
      Improvements in mental status were noted in 14 of 18 patients (77%); eight
      patients (44%) showed more than 50% reductions on the Hamilton scale. Analysis of
      the structure of depressive symptomatology showed that improvement occurred
      because of decreases in anxiety and the severity of somatoform symptoms and, to a
      lesser extent, in melancholy and sleep disturbance. There was no significant
      change in apathy. The decrease in the severity of depression was accompanied by
      an improvement in the quality of life. The efficacy of Coaxil was greater in
      patients with less marked depressive and motor symptoms, shorter durations of
      illness, and less marked cognitive impairments. Coaxil was well tolerated by the
      patients. The data obtained here provide grounds for recommending the use of
      Coaxil in the treatment of depression in PD.

PMID- 17457539
TI  - Applications of RNA interference: current state and prospects for siRNA-based
      strategies in vivo.
AB  - Within the recent years, RNA interference (RNAi) has become an almost-standard
      method for in vitro knockdown of any target gene of interest. Now, one major
      focus is to further explore its potential in vivo, including the development of
      novel therapeutic strategies. From the mechanism, it becomes clear that small
      interfering RNAs (siRNAs) play a pivotal role in triggering RNAi. Thus, the
      efficient delivery of target gene-specific siRNAs is one major challenge in the
      establishment of therapeutic RNAi. Numerous studies, based on different modes of
      administration and various siRNA formulations and/or modifications, have already
      accumulated promising results. This applies to various animal models covering
      viral infections, cancer and multiple other diseases. Continuing efforts will
      lead to the development of efficient and "double-specific" drugs, comprising of
      siRNAs with high target gene specificity and of nanoparticles enhancing siRNA
      delivery and target organ specificity.

PMID- 17457540
TI  - Kinetic studies on autohydrogenotrophic growth of Ralstonia eutropha with nitrate
      as terminal electron acceptor.
AB  - Autohydrogenotrophic batch growth of Ralstonia eutropha H16 was studied in a
      stirred-tank reactor with nitrate and nitrite as terminal electron acceptors and
      the sole limiting substrates. Assuming product inhibition by nitrite, saturation
      kinetics with the two limiting substrates and a simple switching function, which
      allows growth on nitrite only at low nitrate concentrations, resulted in a
      kinetic growth model with nine model parameters. The data of two batch
      experiments were used to identify the kinetic model. The kinetic model was
      validated with two additional batch experiments. The model predictions are in
      very good agreement with the experimental data. The maximum nitrite concentration
      was estimated to be 30.7 mM (total inhibition of growth). After complete
      reduction of nitrate, the growth rate decreases almost to zero before it
      increases again because of the following nitrite respiration. The maximum
      autohydrogenotrophic growth rate of Ralstonia eutropha with nitrate as a final
      electron acceptor (0.509 d(-1)) was found to be reduced by 90-95% compared to the
      so far reported autohydrogenotrophic growth rates with oxygen.

PMID- 17457541
TI  - Repeated pH-stat fed-batch fermentation for rhamnolipid production with
      indigenous Pseudomonas aeruginosa S2.
AB  - Rhamnolipid is one of the most commonly used biosurfactants with the ability to
      reduce the surface tension of water from 72 to 30 mN/m. An indigenous isolate
      Pseudomonas aeruginosa S2 possessing excellent ability to produce rhamnolipid was
      used as a model strain to explore fermentation technology for rhamnolipid
      production. Using optimal medium and operating conditions (37 degrees C, pH 6.8,
      and 250 rpm agitation) obtained from batch fermentation, P. aeruginosa S2 was
      able to produce up to 5.31 g/l of rhamnolipid from glucose-based medium. To
      further improve the rhamnolipid yield, a pH-stat fed-batch culture was performed
      by maintaining a constant pH of 6.8 through manipulating glucose feeding. The
      effect of influent glucose concentration on rhamnolipid yield and productivity
      was investigated. Using the pH-stat culture, a maximum rhamnolipid concentration
      (6.06 g/l) and production rate (172.5 ml/h/l) was obtained with 6% glucose in the
      feed. Moreover, combining pH-stat culture with fill-and-draw operation allowed a
      stable repeated fed-batch operation for approximately 500 h. A marked increase in
      rhamnolipid production was achieved, leading to the best rhamnolipid yield of
      approximately 9.4 g/l during the second repeated run.

PMID- 17457542
TI  - Starvation is not a prerequisite for the formation of aerobic granules.
AB  - Activated sludge with sludge volume index (SVI)(30) of 77 ml g(-1) and SVI(30) of
      433 ml g(-1) was inoculated to start up reactors R1 and R2, respectively. In both
      R1 and R2, cycle time of 1 h and the influent chemical oxygen demand (COD)
      concentrations of 1,000 mg l(-1) were employed. Initial settling time of 2 min
      resulted in the loss of a substantial amount of biomass as wash-out and high
      effluent COD concentrations within the first week of operation. This implied that
      there was no starvation phase in each cycle of R1 and R2 during the first week of
      operation. However, aerobic granules with a size above 400 mum formed by day 7.
      Thus, it was concluded that starvation was not a prerequisite for the formation
      of aerobic granules. When cycle time was 1 h, the instability of aerobic granules
      was observed. When cycle time was prolonged to 1.5 h and granular sludge of 200
      ml was used to start up reactor R3, the reactor R3 reached steady state within 1
      week. SVI, size, and the morphology of granular sludge in R3 remained stable
      during the 47-day operation, which indicated that prolonged starvation time had
      positive effects on the stability of aerobic granules.

PMID- 17457543
TI  - Biosynthesis, properties and potential of natural-synthetic hybrids of
      polyhydroxyalkanoates and polyethylene glycols.
AB  - Chemical conjugation with poly(ethylene glycols) (PEGs) are established
      procedures to facilitate solubilisation of hydrophobic compounds. Such techniques
      for PEGylation have been applied to polyhydroxybutyrate. 'BioPEGylation' of such
      polyhydroxyalkanoates (PHAs) to form natural-synthetic hybrids has been
      demonstrated through the addition of PEGs to microbial cultivation systems. The
      strategic addition of certain PEGs not only supports hybrid synthesis but may
      also provide a technique for control of PHA composition and molecular mass, and
      by extension, their physico-mechanical properties. PHA composition and molecular
      mass control by PEGs is dependent upon the polyethers' molecular mass, loading in
      the cultivation system, time of introduction and microbial species. Hybrid
      characterisation studies are in their infancy, but results to date suggest that
      PHA-PEG hybrids have subtle, but significant, differences in their physiochemical
      and material properties as a consequence of the PEGylation.

PMID- 17457544
TI  - Hypoglycemic effects of exopolysaccharides produced by mycelial cultures of two
      different mushrooms Tremella fuciformis and Phellinus baumii in ob/ob mice.
AB  - The anti-diabetic activities of the exopolysaccharides (EPS) produced by
      submerged mycelial culture of two different mushrooms, Tremella fuciformis and
      Phellinus baumii, in ob/ob mice were investigated. All the animals were randomly
      divided into three groups with seven animals in each group: The control group
      received 0.9% NaCl solution; the diabetic groups were treated with EPS from T.
      fuciformis (Tf EPS) and P. baumii (Pb EPS) at the level of 200 mg/kg body weight
      using an oral zoned daily for 52 days. The plasma glucose levels in the EPS-fed
      mice were substantially reduced by about 52% (Tf EPS) and 32% (Pb EPS),
      respectively, as compared to control mice. The results of oral glucose tolerance
      test (OGTT) revealed that both EPS-fed groups significantly increased the glucose
      disposal after 52 days of EPS treatments. Furthermore, higher food efficiency
      ratios and reduced blood triglyceride levels were observed in the EPS-treated
      groups. Because peroxisome proliferator-activated receptor gamma (PPAR-gamma) is
      indeed a key regulator of insulin action, we investigated the expression pattern
      of adipose tissue PPAR-gamma messenger RNA (mRNA) and plasma levels of PPAR
      gamma. It was revealed that PPAR-gamma was significantly activated in response to
      EPS treatments. The results suggested that both EPS exhibited considerable
      hypoglycemic effect and improved insulin sensitivity possibly through regulating
      PPAR-gamma-mediated lipid metabolism. Our results indicated that two mushroom
      derived EPS might be developed as potential oral hypoglycemic agents or
      functional foods for the management of non-insulin-dependent diabetes mellitus.

PMID- 17457545
TI  - Differential role of microenvironment in microencapsulation for improved cell
      tolerance to stress.
AB  - The effect of the microenvironment in alginate-chitosan-alginate (ACA)
      microcapsules with liquid core (LCM) and solid core (SCM) on the physiology and
      stress tolerance of Sacchromyces cerevisiae was studied. The suspended cells were
      used as control. Cells cultured in liquid core microcapsules showed a nearly
      twofold increase in the intracellular glycerol content, trehalose content, and
      the superoxide dismutase (SOD) activity, which are stress tolerance substances,
      while SCM did not cause the significant physiological variation. In accordance
      with the physiological modification after being challenged with osmotic stress
      (NaCl), oxidative stress (H(2)O(2)), ethanol stress, and heat shock stress, the
      cell survival in LCM was increased. However, SCM can only protect the cells from
      damaging under ethanol stress. Cells released from LCM were more resistant to
      hyperosmotic stress, oxidative stress, and heat shock stress than cells liberated
      from SCM. Based on reasonable analysis, a method was established to estimate the
      effect of microenvironment of LCM and SCM on the protection of cells against
      stress factors. It was found that the resistance of LCM to hyperosmotic stress,
      oxidative stress, and heat shock stress mainly depend on the domestication effect
      of LCM's microenvironment. The physical barrier of LCM constituted by alginate
      chitosan membrane and liquid alginate matrix separated the cells from the damage
      of oxidative stress and ethanol stress. The significant tolerance against ethanol
      stress of SCM attributed to the physical barrier consists of solid alginate
      calcium matrix and alginate-chitosan membrane.

PMID- 17457546
TI  - Are there any differences between nutcracker esophagus with and without reflux?
AB  - "Nutcracker esophagus" (NE) is a primary esophageal motor disorder, first
      described in patients with noncardiac chest pain. In recent years NE has been
      associated with gastroesophageal reflux disease (GERD). In this study we compare
      patients with NE with and without GERD, as defined by pHmetry or endoscopy, with
      respect to clinical, endoscopic, radiologic, and manometric findings. Fifty-two
      patients with NE were studied. They were divided in two groups: GERD (17-32.6%)
      and non-GERD (35-67.4%) patients. Females predominated in both groups, with no
      significant difference in age (p>0.05). Chest pain was the chief complaint in
      both groups (p>0.05). Clinical findings in patients with and without reflux
      included chest pain (52.9% and 51.4%), dysphagia (58.8% and 42.8%), and heartburn
      (64.7% and 42.8%), followed by regurgitation, dyspepsia, ear, nose, and throat
      (ENT) complaints, respiratory symptoms, and odynophagia (p>0.05). Erosive
      esophagitis was found in three patients (5.7%). There were no differences between
      groups in the findings of barium swallow studies and all manometric findings were
      similar for both groups (p>0.05). We conclude that there were no differences in
      patients with NE with or without associated reflux disease. It is important to
      diagnose reflux properly so patients can be treated adequately.

PMID- 17457547
TI  - Dysphagia evaluation practices of speech and language therapists in Ireland:
      clinical assessment and instrumental examination decision-making.
AB  - The purpose of this study was to investigate clinical assessment practices and
      instrumental examination decision-making by speech and language therapists (SLTs)
      in Ireland. A 21-question survey (including patient scenarios) was sent to 480
      SLTs in Ireland. A total of 261 completed surveys were returned (54%), providing
      demographic information on SLTs currently working in Ireland and their services.
      Of these 261 surveys, 70 provided the data for the study, focusing on SLTs
      currently working in dysphagia, with adults/seniors at least some of the time.
      The results also showed clinician variability regarding which components are
      included in a bedside clinical examination of swallowing, with a high degree of
      consistency for only 11 of the 20 components. Clinicians agreed in their
      instrumental vs. noninstrumental evaluation recommendations for two of the six
      patient scenarios, with wide variability in clinical decision-making. Possible
      influences on clinical decision-making are discussed in relation to the findings
      of similar previous studies, as well as the current status and future needs of
      dysphagia training and services in Ireland.

PMID- 17457548
TI  - Reliability and validity of cervical auscultation.
AB  - We conducted a two-part study that contributes to the discussion about cervical
      auscultation (CA) as a scientifically justifiable and medically useful tool to
      identify patients with a high risk of aspiration/penetration. We sought to
      determine (1) acoustic features that mark a deglutition act as dysphagic; (2)
      acoustic changes in healthy older deglutition profiles compared with those of
      younger adults; (3) the correctness and concordance of rater judgments based on
      CA; and (4) if education in CA improves individual reliability. The first part of
      the study focused on a comparison of the "swallow morphology" of dysphagic as
      opposed to healthy subjects' deglutition in terms of structure properties of the
      pharyngeal phase of deglutition. We obtained the following results. The duration
      of deglutition apnea is significantly higher in the older group than in the
      younger one. Comparing the younger group and the dysphagic group we found
      significant differences in duration of deglutition apnea, onset time, and number
      of gulps. Just one parameter, number of gulps, distinguishes significantly
      between the older and the dysphagic groups. The second part of the study aimed at
      evaluating the reliability of CA in detecting dysphagia measured as the
      concordance and the correctness of CA experts in classifying swallowing sounds.
      The interrater reliability coefficient AC1 resulted in a value of 0.46, which is
      to be interpreted as fair agreement. Furthermore, we found that comparison with
      radiologically defined aspiration/penetration for the group of experts (speech
      and language therapists) yielded 70% specificity and 94% sensitivity. We conclude
      that the swallowing sounds contain audible cues that should, in principle, permit
      reliable classification and view CA as an early warning system for identifying
      patients with a high risk of aspiration/penetration; however, it is not
      appropriate as a stand-alone tool.

PMID- 17457549
TI  - Strength-training exercise in dysphagia rehabilitation: principles, procedures,
      and directions for future research.
AB  - Dysphagia rehabilitation, historically, has focused a great deal on various
      compensations during swallowing to prevent aspiration and/or improve safety and
      efficiency. Exercise, in general, has been a part of the dysphagia rehabilitation
      landscape. However, heightened discussions in the field regarding best practices
      for exercise training, particularly strengthening, raise more questions than
      answers. The intent of this paper is to (1) explore the overriding principles of
      neuromuscular plasticity with regard to strength training, (2) evaluate how
      current exercise-training interventions in dysphagia rehabilitation correspond to
      these principles, and (3) postulate directions for future study of normal and
      disordered swallowing and determine how to incorporate these principles into
      dysphagia rehabilitation.

PMID- 17457551
TI  - [Minimally invasive surgery and the economics of it. Can minimally invasive
      surgery be cost efficient from a business point of view?].
AB  - Minimally invasive surgery (MIS) is now accepted as equally valid as the use of a
      standard access in some areas of surgery. It is not possible to decide whether
      this access is economically worthwhile and if so for whom without a full economic
      cost-benefit analysis, which must take account of the hospital's own
      characteristics in addition to the cost involved for surgery, staff,
      infrastructure and administration. In summary, the main economic advantage of MIS
      lies in the patient-related early postoperative results, while the main
      disadvantage is that the operative material costs are higher. At present, the
      payment made for each procedure performed under the DRG system includes 14-17% of
      the total cost for materials, regardless of the access route and of the technical
      sophistication of the operation. The actual material costs are greater by a
      factor of 2-50 for MIS than for a conventional procedure. The task of the
      hospital is thus to lower the costs for material and infrastructure; that of
      industry is to offer less expensive alternatives; and that of our politicians, to
      implement better remuneration of the material costs.

PMID- 17457552
TI  - Biodiversity below ground: probing the subterranean ant fauna of Amazonia.
AB  - Ants are abundant, diverse, and ecologically dominant in tropical forests.
      Subterranean ants in particular are thought to have a significant environmental
      impact, although difficulties associated with collecting ants underground and
      examining their ecology and behavior have limited research. In this paper, we
      present the results of a study of subterranean ant diversity in Amazonian Ecuador
      that employs a novel probe to facilitate the discovery of species inhabiting the
      soil horizon. Forty-seven species of ants in 19 genera, including new and
      apparently rare species, were collected in probes. Approximately 19% of the
      species collected at different depths in the soil were unique to probe samples.
      Analysis of similarity (ANOSIM) results showed that the species composition of
      ants collected with the probe was significantly different from samples collected
      using other techniques. Additionally, ANOSIM computations indicated the species
      assemblage of ants collected 12.5 cm below the surface was significantly
      different from those found at 25, 37.5, and 50 cm. Ant diversity and species
      accumulation rates decreased with increasing depth. There were no species unique
      to the lowest depths, suggesting that subterranean ants may not be distributed
      deep in the soil in Amazonia due to the high water table. The technique we
      describe could be used to gain new insights into the distribution and biology of
      subterranean ant species and other members of the species-rich soil invertebrate
      macrofauna.

PMID- 17457553
TI  - Cosmic vacuum energy decay and creation of cosmic matter.
AB  - In the more recent literature on cosmological evolutions of the universe, the
      cosmic vacuum energy has become a nonrenouncable ingredient. The cosmological
      constant Lambda, first invented by Einstein, but later also rejected by him,
      presently experiences an astonishing revival. Interestingly enough, it acts like
      a constant vacuum energy density would also do. Namely, it has an accelerating
      action on cosmic dynamics, without which, as it appears, presently obtained
      cosmological data cannot be conciliated with theory. As we are going to show in
      this review, however, the concept of a constant vacuum energy density is
      unsatisfactory for very basic reasons because it would claim for a physical
      reality that acts upon spacetime and matter dynamics without itself being acted
      upon by spacetime or matter.

PMID- 17457554
TI  - [High usage of zolpidem and zopiclone. Cross-sectional study using claims data].
AB  - BACKGROUND: Case reports indicate dose increase, abuse, and dependence concerning
      zolpidem and zopiclone (so-called Z-drugs). METHODS: We conducted a cross
      sectional study between 1 July and 31 December 2004 using claims data of the
      German health insurer Gmuender ErsatzKasse to examine high usage of these drugs.
      RESULTS: A total of 6959 subjects bought at least one packet of zolpidem or
      zopiclone, including 20.9% containing 90 daily doses (DDD) or more. High usage,
      defined as at least 180 DDD, was identified in 501 subjects (7.2%). Compared to
      other use, high usage was associated with GP visits only for the prescription of
      Z-drugs (odds ratio 2.01, 95% confidence interval 1.52-2.67), neuroleptics (odds
      ratio 2.53, 95% confidence interval 2.02-3.18), and polypharmacy (odds ratio
      2.40, 95% confidence interval 1.84-3.15). CONCLUSION: Zolpidem and zopiclone are
      often prescribed in higher doses or for long-term use. Such therapy regimens
      should be viewed critically.

PMID- 17457555
TI  - [Illegal purchase of psychotropic drugs from the internet].
AB  - Several national institutions are registering a significant increase in sales of
      prescription and illegal drugs from internet pharmacies. Psychoactive drugs are
      preferred; the clients are particularly young. Considering the current amount of
      data available, the extent and relevance to addiction medicine remain unclear. In
      the following report we present the case of a patient from our outpatient
      department who has suffered from an opioid dependency for several years and has
      been using a Spanish internet pharmacy to purchase tramadol without prescription.

PMID- 17457556
TI  - [The psychopathology of "as if" experiences].
AB  - After a descriptive phenomenological sketch, we try to elucidate the structure of
      the "as if" experience. This experience is concerned with appearance, with what
      'seems' to a person as opposed to actual reality. Normally there is always the
      possibility of error trying to recognize reality, which is accessible to anybody.
      In contrast, for the individual no error is possible regarding an appearance
      which is accessible to nobody but the person to whom it appears. In daily life we
      are often unaware of the confusions of reality and appearance. The obsessive
      patient cannot permit himself such customary confusions. The delusional patient
      cannot realize relevant confusions of reality and appearance, in spite of
      encounters with outside persons. As mentioned, reality and appearance get
      pathologically entangled in both obsessive and delusional patients. Some
      therapeutic proposals are offered from the standpoint of these "as if" patents.

PMID- 17457557
TI  - [Clinical and diagnostic characteristics of T1 root syndrome].
AB  - BACKGROUND: Among radicular lesions, those affecting the T1 root are rare.
      Together with the similarity of symptoms to C8 syndrome, which is more common,
      this makes the diagnosis of T1 radiculopathy complicated. The clinical and
      diagnostic specifics of T1 syndrome are shown here based on three cases.
      MATERIALS AND RESULTS: We report on three patients with T1 syndrome. Clinical
      diagnostics (clinical investigation, electrophysiology, MRI) showed in two cases
      lateral intraforaminal disc herniae at the T1-2 level, and the third patient had
      metastasis of a cervix carcinoma being responsible for the radiculopathy. In all
      cases surgery was performed. The patients with disc herniae were immediately pain
      free after surgery; in the third patient the neurological symptoms and pain
      clearly improved. CONCLUSIONS: These three cases show that by thorough analysis
      of clinical symptoms and functional (electrophysiology) and morphological (MRI)
      diagnostics, T1 radiculopathy can be differentiated from C8 lesions. All of the
      patients benefited from decompressive surgery.

PMID- 17457558
TI  - [Early neurological-neurosurgical rehabilitation. Current state].
AB  - In German neurorehabilitation, the ambiguous term "early rehabilitation" reflects
      the multidisciplinary, rehabilitative treatment of severely impaired patients in
      continuing need of acute and intensive care (including weaning from the
      respirator in selected cases). The actual definition of this treatment is
      discussed, which hitherto corresponded to Phase B according to recommendations of
      the German Federal Study Group for Rehabilitation (BAR) and now has started to be
      integrated into the diagnosis-related group system. The tasks and aims of early
      rehabilitation are to support and enhance neuroplastic remission of nervous
      system functional loss and continued medical care, improve vigilance, establish
      cooperativity, and evaluate the rehabilitation potential including compensatory
      and adaptive strategies organizing posthospital care, reducing the need of
      nursing support, and improving quality of life. Some special aspects of early
      rehabilitative care are presented here in more detail. To fulfill these tasks, a
      multidisciplinary team is required including various therapists qualified for
      neurorehabilition, physicians (including a neurologist), nurses, and social
      workers. Outcome data were assessed using our 5-year prospective early
      rehabilitation registry. Fifty-five percent of patients improved to reach the
      next step of neurorehabilitation (Phase C), with significant gain in function
      even in the subgroup of aged and most severely disabled patients. The trend to
      transfer patients very early in the postacute Phase to early rehabilitation
      facilities, with open medical problems and increased risk of complications, makes
      close cooperation and interaction with acute medical centers necessary.

PMID- 17457560
TI  - [The influence of diet on mental health].
AB  - The influence of nutritional factors on brain metabolism and the course of mental
      illness are increasingly being addressed in international research. It is a
      matter of discussion whether dietary habits, e.g., the amount of fish or
      vegetables, have an effect on the incidence of certain illnesses. Furthermore an
      optimized or supplemented diet could offer therapeutic possibilities; one example
      is the role of polyunsaturated fatty acids as an add-on therapy in affective
      disorders. The limitations of psychopharmacotherapy (drug interactions, side
      effects, noncompliance) underline the theoretical and practical relevance of
      nutrition in mental illness, the more so as mentally ill patients (especially
      when demented, anorectic, depressed, or schizophrenic) are at higher risk of
      malnutrition anyway. Even if the therapeutic evidence is still limited and the
      effects may be relatively weak, nutritional assessment and an optimized diet can
      be recommended for every patient.

PMID- 17457561
TI  - [Rete compensation in agenesis of the internal carotid artery].
AB  - The term carotid rete mirabile refers to an anatomic structure common in several
      lower mammals (e.g., swine). The blood supply for the intracranial arteries
      originates from branches of the external carotid artery, predominantly the
      ascending pharyngeal and internal maxillary arteries. In these animals the
      intracranial internal carotid artery forms from a dense network of numerous
      converging, small-caliber vessels. An analogous structure is rarely found in
      humans. Associated with segmental agenesis of the internal carotid artery, so
      called carotid rete mirabile can be observed. In it numerous tortuous vessels
      with a diameter of 1-2 mm are found along the expected course of the internal
      carotid artery and coming from branches of the external carotid artery. These
      vessels converge to the intradural paraclinoid segment of the internal carotid
      artery, which shows a normal diameter. This rare pattern of collateral supply to
      the brain is illustrated here on the basis of two clinical case histories. Both
      patients presented with aneurysmal subarachnoid hemorrhage. In one, histological
      examination of a vessel biopsy revealed medial fibromuscular dysplasia. In both
      patients the rete mirabile was found in only one carotid system. The affected
      carotid canal in the skull base was hypoplastic. Human carotid rete mirabile
      probably has no inherent pathologic significance, but its frequent association
      with other intra- and extracranial vascular pathologies should be kept in mind.

PMID- 17457562
TI  - [Management of refractory status epilepticus from a neurologic and neuropediatric
      perspective].
AB  - Status epilepticus is a frequent neurologic emergency that is refractory to
      benzodiazepines and phenytoin in 60% to 70% of cases. Patients commonly require
      management in an intensive care unit incorporating aggressive treatment with
      intravenous anaesthetics. Treatment guidelines commonly comment on initial
      pharmacologic management in detail, as they can refer to data from randomised
      controlled trials. In contrast, recommendations for the management of refractory
      status epilepticus often are sparse, as they rely on data from retrospective or
      uncontrolled prospective studies only. Since status epilepticus is refractory in
      every third patient, a critical analysis of the available data and a review
      focussing on the further management of this condition are urgently needed. The
      Koenigstein Team, a panel of expert epileptologists and neuropediatricians,
      discussed at its 31(st) meeting in March 2006 the clinical and experimental
      aspects and implicit prognostic variables of refractory status epilepticus. Here
      we present the results of that discussion and state recommendations from a
      neurologic and neuropediatric perspective for current und future management of
      refractory status epilepticus.

PMID- 17457563
TI  - [Vena cava filter].
AB  - Fulminant pulmonary embolism is one of the major causes of death in the Western
      World. In most cases, deep leg and pelvic venous thrombosis are the cause. If an
      anticoagulant/thrombotic therapy is no longer possible or ineffective, a vena
      cava filter implant may be indicated if an embolism is threatening. Implantation
      of the filter is a simple and safe intervention. Nevertheless, it is necessary to
      take into consideration that the data base for determining the indications for
      this treatment are very limited. Currently, a reduction in the risk of
      thromboembolism with the use of filters of about 30%, of recurrences of almost 5%
      and fatal pulmonary embolism of 1% has been reported, with a risk of up to 20% of
      filter induced vena cava thrombosis.

PMID- 17457564
TI  - Changing perspectives in diabetes: their impact on its classification.
AB  - Type 1 and type 2 diabetes are usually regarded as distinct disorders, but the
      convergence of their phenotypes over recent years, the relationship of body
      weight to the risk of type 1 diabetes, the diminishing importance of the type 1
      susceptibility genes and the finding of autoantibodies in patients with type 2
      diabetes, invite a different interpretation. The possibility that type 1 and type
      2 diabetes, rather than being different, are merely poles of a single spectrum,
      where variation in the tempo of beta cell loss determines age at onset and
      symptoms at presentation, has important implications. Correct classification is
      crucial because it directs appropriate treatment and, where available,
      prevention. This article argues that type 1 diabetes is currently misclassified,
      provides evidence that insulin resistance drives type 1 diabetes as it does type
      2, and proposes how the 'accelerator hypothesis' can be tested in a randomised
      controlled trial, which could demonstrate, for the first time, the safe and
      effective prevention of type 1 diabetes.

PMID- 17457565
TI  - Directed differentiation of human embryonic stem cells towards a pancreatic cell
      fate.
AB  - AIMS/HYPOTHESIS: The relative lack of successful pancreatic differentiation of
      human embryonic stem cells (hESCs) may suggest that directed differentiation of
      hESCs into definitive endoderm and subsequent commitment towards a pancreatic
      fate are not readily achieved. The aim of this study was to investigate whether
      sequential exposure of hESCs to epigenetic signals that mimic in vivo pancreatic
      development can efficiently generate pancreatic endodermal cells, and whether
      these cells can be further matured and reverse hyperglycaemia upon
      transplantation. MATERIALS AND METHODS: The hESCs were sequentially treated with
      serum, activin and retinoic acid (RA) during embryoid body formation. The
      patterns of gene expression and protein production associated with embryonic germ
      layers and pancreatic endoderm were analysed by RT-PCR and immunostaining. The
      developmental competence and function of hESC-derived PDX1-positive cells were
      evaluated after in vivo transplantation. RESULTS: Sequential treatment with
      serum, activin and RA highly upregulated the expression of the genes encoding
      forkhead box protein A2 (FOXA2), SRY-box containing gene 17 (SOX17), pancreatic
      and duodenal homeobox 1 (PDX1) and homeobox HB9 (HLXB9). The population of
      pancreatic endodermal cells that produced PDX1 was significantly increased at the
      expense of ectodermal differentiation, and a subset of the PDX1-positive cells
      also produced FOXA2, caudal-type homeobox transcription factor 2 (CDX2), and
      nestin (NES). After transplantation, the PDX1-positive cells further
      differentiated into mature cell types producing insulin and glucagon, resulting
      in amelioration of hyperglycaemia and weight loss in streptozotocin-treated
      diabetic mice. CONCLUSIONS/INTERPRETATION: Our strategy allows the progressive
      differentiation of hESCs into pancreatic endoderm capable of generating mature
      pancreatic cell types that function in vivo. These findings may establish the
      basis of further investigations for the purification of transplantable islet
      progenitors derived from hESCs.

PMID- 17457566
TI  - [Axes of the legs in childhood. What is pathologic?].
AB  - At birth the lower extremity is characterized by a varus axis in the lower leg
      and the knee joint in the frontal plane (bowleg) and an increased femoral
      antetorsion and a neutral or increased medial torsion of the lower leg in the
      transverse plane. By the time growth is complete a normal valgus axis of 5-9
      degrees has developed in the lower limb and the femoral antetorsion has decreased
      to about 15 degrees. The lower leg will show a normal external rotation of 15
      degrees on average. The evolution of the axis values in the lower extremity is
      influenced by changing compressive and propelling forces acting on the growth
      plates as the child adopts an upright posture. There is a wide range of normal
      values, but pathologic development of the leg axes is rare and mostly idiopathic.
      Secondary deviations of the axis from normal can occur. Careful clinical
      examinations are necessary to differentiate between pathologic and physiological
      variations. Further apparative diagnostic procedures help to elucidate the
      etiology and are essential for surgical planning. Nonoperative treatment alone is
      rarely sufficient to influence the deformity.

PMID- 17457567
TI  - [Ulna shortening osteotomy using a new 7 hole gliding plate. Results from 73
      cases].
AB  - BACKGROUND: Ulna shortening osteotomy is a common procedure for the surgical
      treatment of ulna impaction syndrome, but it is still associated with
      complications such as rotation malalignment, and delayed or non-union due to of
      incomplete closure of the osteotomy gap. METHODS: We have developed a 7-hole
      titanium compression plate that provides fixation of the ulna before the
      osteotomy is carried out. With this plate, which has been in use for 4 years, a
      shortening of up to 10 mm is possible using two gliding holes, with the
      compression holes enabling the closure of the osteotomy gap. We report the
      results of 70 patients undergoing 70 ulna shortening procedures, with a follow-up
      of between 5 and 18 months. Two patient groups underwent follow-up clinical
      examination as well as completing the Disabilities of the Arm, Shoulder and Hand
      (DASH) questionnaire for evaluation. RESULTS AND CONCLUSIONS: There was no
      occurrence of delayed or non-union. The DASH score averaged 19 points in the
      prospective and 23 points in the retrospective group, representing a good
      functional result with only minor impairment. This study indicates that ulnar
      shortening using this gliding compression plate and performing an oblique
      osteotomy is associated with a minimal complication rate and highly satisfactory
      clinical outcome.

PMID- 17457568
TI  - Measurement of respiratory system resistance during mechanical ventilation.
AB  - BACKGROUND: The measurement of respiratory system resistance during mechanical
      ventilation is important to ascertain the causes of increase in airway pressure
      during volume-controlled ventilation, which may include airways resistance and
      decreased respiratory system compliance. DISCUSSION: Separation of total
      resistance from compliance of the respiratory system can be assessed by the end
      inspiratory hold maneuver that separates peak pressure from plateau pressure.
      CONCLUSIONS: Although this method assumes a homogeneous respiratory system, it
      has proven useful clinically to separate flow-dependence issues such as
      bronchospasm or endotracheal tube obstruction from stiff lungs (acute lung
      injury) or decrease chest wall (abdominal distension) compliance.

PMID- 17457569
TI  - Internal jugular venous catheter-related bacteremia according to central and
      posterior accesses.
AB  - BACKGROUND: Although there are many studies about central venous catheter-related
      infection, we have not found any analysis of the incidence of internal jugular
      venous catheter-related bacteremia associated with different accesses. OBJECTIVE:
      The objective of this study was to test whether the position of the internal
      jugular venous catheter, central or posterior, influences the incidence of
      bacteremia. DESIGN: A cohort study. SETTING: A 12-bed polyvalent medical-surgical
      intensive care unit (ICU). PATIENTS: Patients admitted to ICU between 1 May 2000
      and 30 April 2004 who received one or more internal jugular venous catheters.
      MEASUREMENTS AND RESULTS: A total of 1,483 patients were admitted to the
      polyvalent ICU, of whom 1,311 underwent central venous catheterization. A total
      of 547 patients received 684 internal jugular venous catheters, 169 by posterior
      and 515 by central access. There were no significant differences between central
      and posterior access patients in sex, age, APACHE II (14.1 +/- 5.0 vs. 13.9 +/-
      5.2, p = 0.40), diagnosis, order of catheter insertion, use of mechanical
      ventilation, use of antimicrobials, use of total parenteral nutrition or use of
      pulmonary artery catheter. We found a higher incidence of internal jugular venous
      catheter-related bacteremia with central (4.8 per 1000 catheter-day) than with
      posterior (1.2 per 1000 catheter-day) access (odds ratio 3.9; 95% confidence
      interval 1.1-infinite; p = 0.03). CONCLUSION: Posterior access has a lower
      incidence of internal jugular venous catheter-related bacteremia than central
      access in non-severely ill patients (according to the low APACHE II score values
      of the study patients).

PMID- 17457570
TI  - Traumatic pediatric brain injury and intracranial pressure monitoring: does it
      really improve outcome?

PMID- 17457571
TI  - Pediatric delirium in critical illness: phenomenology, clinical correlates and
      treatment response in 40 cases in the pediatric intensive care unit.
AB  - OBJECTIVE: To study the phenomenology, clinical correlates, and response to
      treatment of delirium in critically ill children in the pediatric intensive care
      unit (PICU). DESIGN, SETTING AND PATIENTS: Descriptive study of a cohort of child
      psychiatric consultations from a tertiary PICU between January 2002 and December
      2005. Demographic data, clinical presentation, and response to treatment of
      children subsequently diagnosed with delirium were analyzed. RESULTS: Out of 877
      admissions (age distribution 0-18 years) arose 61 requests for psychiatric
      assessment. Of the 61 children, 40 (15 girls and 25 boys) were diagnosed with
      delirium (cumulative incidence 5%; mean age 7.6 years). Age-specific incidence
      rates varied from 3% (0-3 years) to 19% (16-18 years). In addition to the
      classical hypoactive and hyperactive presentations, a third presentation was
      apparent, characterized mainly by anxiety, with a higher prevalence in boys. All
      but 2 of the 40 children received antipsychotic medication: 27 (68%) haloperidol,
      10 (25%) risperidone, and 1 both in succession. Two children treated with
      haloperidol experienced an acute torticollis as side effect. All children made a
      complete recovery from the delirium; five, however, died of their underlying
      disease. CONCLUSION: The rate of delirium in critically ill children on a PICU is
      not negligible, yet prospective studies of the phenomenology, risk factors and
      treatment of childhood delirium are very rare. Once pediatric delirium has been
      recognized, it generally responds well to treatment.

PMID- 17457572
TI  - Some more applications of transcranial Doppler in the ICU.

PMID- 17457573
TI  - Postresuscitation accelerated idioventricular rhythm: a potential prognostic
      factor for out-of-hospital cardiac arrest survivors.
AB  - OBJECTIVE: Data are lacking on the relationship between postresuscitation ECG and
      outcome in out-of-hospital cardiac arrest (OHCA). We examined the prognostic
      information that postresuscitation ECG rhythm can provide for predicting outcome
      in OHCA survivors. METHODS: The retrospective observational study enrolled 56
      successfully resuscitated nontraumatic adult OHCA patients. Postresuscitation 12
      lead ECGs of the enrolled patients were interpreted independently by two
      cardiologists. We compared baseline clinical characteristics, CPR process, and
      outcome in the 8 patients with postresuscitation accelerated idioventricular
      rhythm (AIVR, n = 8) and the 48 without AIVR. RESULTS: The AIVR group had a
      higher proportion of patients with coronary artery disease (50% vs. 15%), initial
      ventricular tachycardia/fibrillation rhythm (50% vs. 8%), and cardiac origin of
      OHCA (75% vs. 23%). AIVR patients had longer total CPR duration (32 vs. 18 min)
      and higher dose of epinephrine use (10 vs. 3 mg). Postresuscitation AIVR was
      associated with an increased incidence of repeated CPR within 1 h after return of
      spontaneous circulation (38% vs. 4%), and lower 7-day survival rate (0% vs. 50%).
      CONCLUSIONS: AIVR on postresuscitation ECG offers a prognostic factor related to
      a higher repeated CPR rate within 1h after return of spontaneous circulation and
      a lower 7-day survival rates in successfully resuscitated OHCA victims.

PMID- 17457574
TI  - The effect of activated protein C on plasma cytokine levels in a porcine model of
      acute endotoxemia.
AB  - OBJECTIVE: To assess the anti-inflammatory effects of recombinant human activated
      protein C (rhAPC) in a porcine model of acute endotoxemia. DESIGN AND SETTING:
      Animal randomized controlled study at the Laboratory of Clinical Institute,
      Aarhus University Hospital. SUBJECTS: Eighteen female landrace pigs (30 kg).
      INTERVENTIONS: By pairwise randomization, pigs were given either LPS or LPS and
      rhAPC. Both groups received a stepwise increasing LPS infusion for 30[Symbol: see
      text]min; whereafter the infusion continued at a lower rate (300 min LPS in both
      groups). The LPS+rhAPC group received rhAPC (100 microg/kg per hour) 15 min
      before the LPS infusion began and throughout the trial period. RESULTS: While
      rhAPC showed no modifying effects on peak plasma levels of pro- or anti
      inflammatory cytokines (TNF-alpha, IL-6, IL-8, IL-10), TNF-alpha and IL-10 peaked
      significantly later in the rhAPC-treated animals. The profibrinolytic effects of
      rhAPC were confirmed by decreased plasminogen activator inhibitor 1 levels, while
      no differences were found in other coagulation markers, hemodynamic, metabolic,
      or leukocyte data between the two groups. CONCLUSIONS: We found no significant
      effect of rhAPC on plasma levels of either pro- or anti-inflammatory cytokines in
      this porcine model of acute endotoxemia. However, TNF-alpha and IL-10 peaked
      significantly later in the rhAPC-treated animals.

PMID- 17457575
TI  - Influence of intra-operative joint gap on post-operative flexion angle in
      osteoarthritis patients undergoing posterior-stabilized total knee arthroplasty.
AB  - Recently, we developed a new tensor for total knee arthroplasty (TKA) procedures
      enabling soft tissue balance assessment throughout the range of motion while
      reproducing post-operative joint alignment with the patello-femoral (PF) joint
      reduced and the tibiofemoral joint aligned. Using the tensor with a computer
      assisted navigation system, we investigated the relationship between various
      intra-operative joint gap values and their post-operative flexion angles. An
      increased value during the extension to flexion gap and a decreased value during
      the flexion to deep flexion gap with PF joint reduced, not everted, showed an
      inverse correlation with post-operative knee flexion angle, not pre-operative
      flexion angle. In conclusion, understanding the characteristics of joint gap
      kinematics in posterior-stabilized TKA under physiological and reproducible joint
      conditions may enable the prediction of the post-operative flexion angle and help
      to determine the appropriate intra-operative joint gap.

PMID- 17457576
TI  - Revision using modified transglenoid reconstruction in recurred glenohumeral
      instability combined with anchor-induced arthropathy.
AB  - A 25-year-old man presented with a history of pain and crepitus in the right
      shoulder; he had been previously treated with arthroscopic anterior stabilization
      using four metallic suture anchors for recurrent traumatic anterior instability 1
      year earlier. In this report, we present a patient with recurrent glenohumeral
      instability combined with anchor-induced arthropathy who was managed with
      modified arthroscopic transglenoid reconstruction following arthroscopic suture
      anchor retrieval.

PMID- 17457577
TI  - A SLAP lesion associated with calcific tendinitis of the long head of the biceps
      brachii at its origin.
AB  - Calcific tendinitis is a common condition with characteristic clinical and
      radiological findings. Although we do not know which condition initiated the
      pathologic cascade, we present a rare case of calcific tendinitis of the long
      head of the biceps brachii at its origin, associated with a SLAP lesion. The
      calcium deposit was removed and the SLAP lesion was repaired with a suture anchor
      arthroscopically.

PMID- 17457578
TI  - A long-term ecstasy-related change in visual perception.
AB  - RATIONALE: The present study provides the first evidence of the long-term
      consequences of ecstasy use on visual processes thought to reflect serotonergic
      functions in the occipital lobe. Methylenedioxymethamphetamine ("ecstasy") is
      known to cause lasting changes to the serotonin system in animals, and convergent
      evidence suggests that similar changes occur in human ecstasy users. Other
      research suggests that serotonin may be involved in lateral inhibition between
      orientation sensitive neurons in the occipital lobe, and that disruption to the
      serotonin system causes an increase in the magnitude of the tilt aftereffect
      illusion that is known depend on those neurons. OBJECTIVES: The aim of the
      present study was to determine if ecstasy users have detectable changes in
      occipital lobe behavioural functioning, as revealed by the tilt aftereffect
      illusion. MATERIALS AND METHODS: Thirty ecstasy users and 34 non-drug using
      controls were compared on the magnitude of the tilt aftereffect illusion
      following adaptation to stimuli oriented at 15 and 40 degrees from vertical.
      RESULTS: Ecstasy users who had not used amphetamines for 115 days or more had a
      larger average tilt aftereffect than non-drug using controls after adaptation to
      40 degrees stimuli but not after adaptation to 15 degrees stimuli. Additionally,
      there was no difference between non-drug using controls and ecstasy users who had
      used amphetamines within the last 61 days at either adaptation angle.
      CONCLUSIONS: The results were consistent with the proposal that ecstasy-related
      damage to the serotonin system causes behavioural changes on tests of visual
      perception processes that are thought to reflect serotonergic functions in the
      occipital lobe.

PMID- 17457579
TI  - Genotoxic hazard of radiopharmaceuticals in humans: chemical and radiation
      aspects coupled to microdosing.
AB  - INTRODUCTION: To obtain the pharmacokinetic properties of drug candidates at an
      early stage of the development process, a microdosing (phase 0) concept to
      radiolabel drug candidates and administer them at subtoxic mass to a few
      volunteers has been suggested. Radiopharmaceuticals are special in the sense that
      the chemical carrier might be genotoxic, whereas it is well established that
      ionizing radiation coupled to the molecule is genotoxic, and that the mechanism
      that causes cancer is similar to certain genotoxic chemicals. REGULATORY
      PERSPECTIVES OF THE LEVELS OF TOXICITY: An analysis shows that, e.g., positron
      emission tomography (PET) pharmaceuticals carry a mass less than what is regarded
      as an acceptable level of a genotoxic impurity. It has also been shown that the
      estimated genotoxicity hazard of the radioactivity is 10-100 times higher than
      that of the administered chemicals. CONCLUSION: As radiation doses at this level
      are accepted in clinical trials, the conclusion is that the regulatory demands on
      radiopharmaceuticals produced at high specific radioactivity should be
      reconsidered in order to facilitate the use of the microdosing concept for drug
      development.

PMID- 17457580
TI  - Vesicocutaneous fistula caused by giant bladder calculus.
AB  - A rare case of giant bladder calculus presenting with vesicocutaneous fistula is
      described. A 62-year-old woman presented with dysuria and ulcer of the
      hypogastric wall. Urine drained through the ulcer. Both X-ray and computed
      tomography (CT) of the abdomen showed a giant bladder calculus with
      vesicocutaneous fistula. We performed cystolithotomy followed by closure of the
      fistula. The calculus measured 95 x 60 x 55 mm and weighed 350 g. Worldwide, it
      is the second reported case of vesicocutaneous fistula caused by giant bladder
      calculus.

PMID- 17457581
TI  - Multidetector row CT for imaging the paediatric tracheobronchial tree.
AB  - The introduction of multidetector row computed tomography (MDCT) scanners has
      altered the approach to imaging the paediatric thorax. In an environment where
      the rapid acquisition of CT data allows general hospitals to image children
      instead of referring them to specialist paediatric centres, it is vital that
      general radiologists have access to protocols appropriate for paediatric
      applications. Thus a dramatic reduction in the delivered radiation dose is
      ensured with optimal contrast bolus delivery and timing, and inappropriate
      repetition of the scans is avoided. This article focuses on the main principles
      of volumetric CT imaging that apply generically to all MDCT scanners. We describe
      the reconstruction techniques for imaging the paediatric thorax and the low-dose
      protocols used in our institution on a 16-slice detector CT scanner. Examples of
      the commonest clinical applications are also given.

PMID- 17457582
TI  - Low MHC variation in the endangered Galapagos penguin (Spheniscus mendiculus).
AB  - The major histocompatibility complex (MHC) is one of the most polymorphic regions
      of the genome, likely due to balancing selection acting to maintain alleles over
      time. Lack of MHC variability has been attributed to factors such as genetic
      drift in small populations and relaxed selection pressure. The Galapagos penguin
      (Spheniscus mendiculus), endemic to the Galapagos Islands, is the only penguin
      that occurs on the equator. It relies upon cold, nutrient-rich upwellings and
      experiences severe population declines when ocean temperatures rise during El
      Nino events. These bottlenecks, occurring in an already small population, have
      likely resulted in reduced genetic diversity in this species. In this study, we
      used MHC class II exon 2 sequence data from a DRB1-like gene to characterize the
      amount of genetic variation at the MHC in 30 Galapagos penguins, as well as one
      Magellanic penguin (S. magellanicus) and two king penguins (Aptenodytes
      patagonicus), and compared it to that in five other penguin species for which
      published data exist. We found that the Galapagos penguin had the lowest MHC
      diversity (as measured by number of polymorphic sites and average divergence
      among alleles) of the eight penguin species studied. A phylogenetic analysis
      showed that Galapagos penguin MHC sequences are most closely related to Humboldt
      penguin (Spheniscus humboldti) sequences, its putative sister species based on
      other loci. An excess of non-synonymous mutations and a pattern of trans-specific
      evolution in the neighbor-joining tree suggest that selection is acting on the
      penguin MHC.

PMID- 17457583
TI  - Evolution of the lung surfactant proteins in birds and mammals.
AB  - Phylogenetic analyses of the families of mammalian lung surfactant proteins (SP
      A, SP-B, SP-C, and SP-D) supported the hypothesis that these proteins have
      diverged between birds and mammals as a result of lineage-specific gene
      duplications and deletions. Homologs of mammalian genes encoding SP-B, SP-C, and
      SP-D appear to have been deleted in chickens, whereas there was evidence of avian
      specific duplications of the genes encoding SP-A and presaposin. Analysis of the
      genes closely linked to human SP-B, SP-C, and SP-D genes revealed that all three
      of these genes are closely linked to genes having orthologs on chicken chromosome
      6 and also to genes lacking chicken orthologs. These relationships suggest that
      all of the lung surfactant protein genes, as well as certain related genes, may
      have been linked in the ancestor of humans and chickens. Further, they imply that
      the loss of surfactant protein genes in the avian lineages formed part of major
      genomic rearrangement events that involved the loss of other genes as well.

PMID- 17457584
TI  - Localization of splenosis using 99mTc-damaged red blood cell SPECT/CT and
      intraoperative gamma probe measurements.

PMID- 17457585
TI  - Radioiodine treatment of hyperthyroidism: fixed or calculated doses; intelligent
      design or science?

PMID- 17457586
TI  - Familial multiple myeloma: first case reported in a Mexican family.

PMID- 17457587
TI  - Continuous model for the rock-scissors-paper game between bacteriocin producing
      bacteria.
AB  - In this work, important aspects of bacteriocin producing bacteria and their
      interplay are elucidated. Various attempts to model the resistant, producer and
      sensitive Escherichia coli strains in the so-called rock-scissors-paper (RSP)
      game had been made in the literature. The question arose whether there is a
      continuous model with a cyclic structure and admitting an oscillatory dynamics as
      observed in various experiments. The May-Leonard system admits a Hopf
      bifurcation, which is, however, degenerate and hence inadequate. The traditional
      differential equation model of the RSP-game cannot be applied either to the
      bacteriocin system because it involves positive interaction terms. In this paper,
      a plausible competitive Lotka-Volterra system model of the RSP game is presented
      and the dynamics generated by that model is analyzed. For the first time, a
      continuous, spatially homogeneous model that describes the competitive
      interaction between bacteriocin-producing, resistant and sensitive bacteria is
      established. The interaction terms have negative coefficients. In some
      experiments, for example, in mice cultures, migration seemed to be essential for
      the reinfection in the RSP cycle. Often statistical and spatial effects such as
      migration and mutation are regarded to be essential for periodicity. Our model
      gives rise to oscillatory dynamics in the RSP game without such effects. Here, a
      normal form description of the limit cycle and conditions for its stability are
      derived. The toxicity of the bacteriocin is used as a bifurcation parameter.
      Exact parameter ranges are obtained for which a stable (robust) limit cycle and a
      stable heteroclinic cycle exist in the three-species game. These parameters are
      in good accordance with the observed relations for the E. coli strains. The roles
      of growth rate and growth yield of the three strains are discussed. Numerical
      calculations show that the sensitive, which might be regarded as the weakest, can
      have the longest sojourn times.

PMID- 17457588
TI  - [Prevalence of diabetic retinopathy. Check-up program of a public health
      insurance company in Germany 2002-2004].
AB  - OBJECTIVES: Population based studies have reported a prevalence of diabetic
      retinopathy (DR) at the time of diagnosis in up to 30% of the patients. In the
      context of a general diabetes check-up program (so called "Diabetes-TUV"), the
      prevalence of diabetic retinopathy in Germany was examined in all diabetes
      patients insured in a public health insurance company. METHODS: Patients were
      screened in the offices of 181 ophthalmologists according to a standardized
      protocol formulated by Prof. Kroll, Marburg. A total of 6,500 sheets were
      analysed out of which 14.5% were multiply documented. The latest protocols of
      5,596 patients were evaluated; the mean age was 64.7 years with an average
      duration of diabetes of 10.2 years. RESULTS: Some 86.3% of the eyes examined had
      no DR, in 3.1% no evaluation was possible. Of the patients checked, 10.6% had DR.
      Mild/moderate DR was reported in 8.3%, severe non-proliferative DR in 1.7% and
      proliferative DR in 0.5%. Macular edema was reported in 0.85% of cases, vitreous
      hemorrhage in 0.2%. There was 0.1% iris neovascularisation and 0.1% retinal
      detachment. Visual impairment due to cataract or secondary cataract was found in
      25.2% of patients with an 8.3% pseudophakia rate. CONCLUSION: Documentation of
      the eye examination in the diabetes check-up program was good. The 10.6%
      prevalence of DR in Germany, even after long standing diabetes, seems to be lower
      than in earlier population based studies in the US or UK. The data reported here
      could be an indication of better diabetes care in Germany. However, not all
      patients were examined with dilated pupils, and in the case of severe changes,
      the ophthalmologist might have decided not to fill in the report form and to have
      chosen another form of communication.

PMID- 17457589
TI  - [Panuveitis with an iris tumor in the chamber angle].

PMID- 17457590
TI  - [Unclear sterile corneal ulcer in a psychologically disturbed patient].

PMID- 17457591
TI  - Circadian rhythms of locomotor activity and temperature selection in sleepy
      lizards, Tiliqua rugosa.
AB  - This study examined whether the daily rhythms of locomotor activity and
      behavioural thermoregulation that have previously been observed in Australian
      sleepy lizards (Tiliqua rugosa) under field conditions are true circadian rhythms
      that persist in constant darkness (DD) and whether these rhythms show similar
      characteristics. Lizards held on laboratory thermal gradients in the Australian
      spring under the prevailing 12-hour light : dark (LD) cycle for 14 days displayed
      robust daily rhythms of behavioural thermoregulation and locomotor activity. In
      the 13-day period of DD that followed LD, most lizards exhibited free-running
      circadian rhythms of locomotor activity and behavioural thermoregulation. The
      predominant activity pattern displayed in LD was unimodal and this was retained
      in DD. While mean levels of skin temperature and locomotor activity were found to
      decrease from LD to DD, activity duration remained unchanged. The present results
      demonstrate for the first time that this species' daily rhythm of locomotor
      activity is an endogenous circadian rhythm. Our results also demonstrate a close
      correlation between the circadian activity and thermoregulatory rhythms in this
      species indicating that the two rhythms are controlled by the same master
      oscillator(s). Future examination of seasonal aspects of these rhythms, may,
      however, cause this hypothesis to be modified.

PMID- 17457592
TI  - Diffuse alterations in synaptic protein expression following focal traumatic
      brain injury in the immature rat.
AB  - INTRODUCTION: The mechanisms responsible for cognitive decline after traumatic
      brain injury (TBI) in pediatric patients are poorly understood. The present study
      examined the potential role of synaptic alterations in this process by using an
      animal model of immature head injury to define the impact of TBI on expression of
      the synaptic protein, synaptophysin. MATERIALS AND METHODS: After craniotomy, TBI
      was induced in postnatal day 17 (PND17) rats using controlled cortical impact
      delivered to the left hemisphere. NeuN, a neuronal marker, and synaptophysin
      expression were examined 1 day, 1 week, and 1 month after injury by
      immunohistochemistry and immunoblotting. RESULTS: There were significant
      decreases in both NeuN and synaptophysin after 1 day and 1 week but not 1 month
      after injury within the hippocampus and neocortex adjacent to the impact site
      compared to sham-injured controls. The decrease in synaptophysin and NeuN was
      also noted in the contralateral hippocampus by 1 day after injury and in the
      contralateral neocortex by 1 week, indicating that changes in protein expression
      were not solely localized to the injury site but occurred in more distant regions
      as well. DISCUSSION: In conclusion, the decrease and recovery in synaptophysin
      parallel the cognitive changes that occur after experimental TBI in the PND17
      rat, which suggests that changes in this protein may contribute to cognitive
      declines after injury. The results also suggest that, in spite of the focal
      nature of the impact, diffuse alterations in protein expression can occur after
      immature TBI and may contribute to the subsequent cognitive dysfunction.

PMID- 17457593
TI  - Multiple pilocytic astrocytomas of the cerebellum in a 17-year-old patient with
      neurofibromatosis type I.
AB  - OBJECTIVE: Approximately 10% of patients with neurofibromatosis I (NFI) patients
      will have central nervous system (CNS) tumors. The most common of these are
      hypothalamic-optic gliomas, followed by brainstem and cerebellar pilocytic
      astrocytomas. While isolated pilocytic astrocytomas in NFI are well described,
      the appearance of multiple pilocytic astrocytomas in an individual patient is
      less common. The most frequent combination in NFI patients with more than one
      pilocytic astrocytoma is optic tract/hypothalamic and brainstem. Other
      combinations are exceedingly rare; multiple pilocytic astrocytomas have only been
      reported once in the cerebral hemispheres in a patient with NFI. This report
      presents the first documented case, to our knowledge, of multiple pilocytic
      astrocytomas in the cerebellum of a patient with NF1. METHODS: Case report.
      CONCLUSION: The finding of multiple cerebellar pilocytic astrocytomas in a
      patient with NF1 is important because it expands the spectrum of presentations
      for patients with NF1 and also highlights specific diagnostic and therapeutic
      challenges faced by the treating physicians. The genetic and molecular basis of
      NF1 is reviewed. Strategies of diagnosis and treatment outlined here are relevant
      to both patients with NF1 and all patients with multiple posterior fossa tumors.

PMID- 17457594
TI  - Valosin-containing protein and the pathogenesis of frontotemporal dementia
      associated with inclusion body myopathy.
AB  - Frontotemporal dementia with inclusion body myopathy and Paget's disease of bone
      (IBMPFD) is a rare, autosomal dominant disorder caused by mutations in the gene
      valosin-containing protein (VCP). The CNS pathology is characterized by a novel
      pattern of ubiquitin pathology distinct from sporadic and familial frontotemporal
      lobar degeneration with ubiquitin-positive inclusions without VCP mutations. Yet,
      the ubiquitin-positive inclusions in IBMPFD also stain for TAR DNA binding
      protein, a feature that links this rare disease with the pathology associated
      with the majority of sporadic FTD as well as disease resulting from different
      genetic alterations. VCP, a member of the AAA-ATPase gene family, associates with
      a plethora of protein adaptors to perform a variety of cellular processes
      including Golgi assembly/disassembly and regulation of the ubiquitin-proteasome
      system. However, the mechanism whereby mutations in VCP lead to CNS, muscle, and
      bone disease is largely unknown. In this report, we review current literature on
      IBMPFD, focusing on the pathology of the disease and the biology of VCP with
      respect to IBMPFD.

PMID- 17457595
TI  - Femoral revision using long hydroxyapatite-coated interlocking stem.
AB  - INTRODUCTION: Cementless femoral revision has become increasingly popular because
      the cementless implants provide the potential for long-term biologic implant
      fixation. The IOTA interlocking femoral stem is a hydroxyapatite-coated stem with
      the option of interlocking the stem distally. The aim of the current study was to
      evaluate the short-term results of IOTA interlocking stem. MATERIALS AND METHODS:
      We retrospectively reviewed the results of 18 total hip arthroplasties in 17
      patients performed between July 2002 and 2004 using the IOTA interlocking stem.
      In-patient records were retrieved and in addition to demographic data the
      indication for revision, the preoperative and postoperative Harris Hip scores,
      need for allografts were noted. The bone deficiency was classified based on the
      AAOS classification. Intraoperative complications and problems if any were
      retrieved from the authors' operative notes. Radiographs at the final follow up
      were evaluated by the criteria described by Engh et al. (Clin Orthop 257:107-128,
      1990) RESULTS: Average age at the time of revision was 57 years. Preoperatively
      five femora showed type I deficiency, type II deficiency was seen in three, type
      III in nine and type IV deficiency in one femur. In five hips the calcar
      replacing prosthesis was implanted to manage the proximal calcar defect, in one
      hip allograft was used to reconstruct the calcar. One patient sustained
      intraoperative fracture of the shaft of the femur while implanting the trial
      prosthesis and one patient had a perforation of the posterior cortex of femur
      while trying to remove the cement. The mean follow up period was 33.5 months
      (range 27-45 months). The mean preoperative Harris Hip score was 36 (range 23
      50), which improved to 77 (range 68-92) at the time of final follow up. None of
      the stems required revision and at minimum 27 months follow up, bony ingrowth was
      noted in 83.33% of the stems. CONCLUSION: IOTA interlocking stem has shown
      promising short-term results for femoral revisions. The advantages are initial
      axial and rotational stability and consistent bony in growth owing to
      hydroxyapatite coating. Intraoperative fracture is a potential drawback because
      of the straight nature of the stem. The calcar replacing option of the stem is
      especially useful in patients with deficient calcar as a substitute for the
      allograft.

PMID- 17457596
TI  - Treatment of the humeral shaft nonunion after surgical failure using the
      Selfdynamisable internal fixator.
AB  - INTRODUCTION: A nonunion of the humeral shaft is not a rare condition and is a
      complication of both nonoperative and operative treatment of the fracture.
      Several fixation options were used in the nonunion treatment, including various
      plate techniques, intramedullary nails and external fixator. We applied our
      Selfdynamisable internal fixator for the treatment of humeral shaft nonunion
      after surgical failure and evaluated its clinical outcome. MATERIALS AND METHODS:
      Six patients with persistent atrophic nonunion of the humeral shaft were treated
      with Selfdynamisable internal fixator. The inclusion criteria were mobile,
      unstable resistant nonunion of the humeral diaphysis which persisted after
      surgical treatment for nonunion. All patients were men with a mean age of 32 (27
      39) years. The initial fracture treatment was external fixator in two patients
      and plaster cast for four patients. All cases failed to unite after primary
      treatment. Plate fixation was resorted for fracture union but failed. The
      revision surgery consisted of removal of hardware, freshening of bone ends and
      bone grafting, and internal fixation with a Selfdynamisable internal fixator.
      RESULTS: The average follow-up was 33 months. All the nonunions healed after
      indexed operation. The average time for union was 5.5 months (range 4-9 months).
      There was no loosening or breakage of the fixation device. The functional
      results, according to the scale of Constant and Murlay modified by Ring, were
      excellent in five and good in one patient. There were no complications of nerve
      injuries or infections related to the operation. CONCLUSION: Selfdynamisable
      internal fixator with bone graft for the treatment of recalcitrant humeral shaft
      nonunion provided successful clinical outcome with minimal complications.

PMID- 17457597
TI  - Mechanical evaluation of different techniques for Achilles tendon repair.
AB  - INTRODUCTION: One aim of the surgical treatment of acute Achilles tendon ruptures
      is to obtain a maximum primary stability of the sutured tendon. Therefore, we
      investigated the primary stability of sutured human Achilles tendons depending on
      different applied techniques. METHODS: The strength of 60 repaired cadaveric
      human Achilles tendons was tested depending on either the suture technique
      (Bunnell or Kessler), the suture material (PDS-thread or PDS-cord) or an
      additional plantaris tendon augmentation (PDS-thread with or without
      augmentation). Following anatomic reconstruction the repaired specimens were
      loaded to failure. RESULTS: The use of Bunnell's technique resulted in a stronger
      primary suture stability compared to Kessler's technique. Sutures carried out
      with a PDS-thread were of lower strength than those accomplished with a PDS-cord
      (Bunnell: thread 139 N +/- 29.8; cord 291 N +/- 55.2/Kessler: thread 137 N +/-
      37.3; cord 180 N +/- 41.1). Sutures performed according to Bunnell's technique
      with a PDS-thread and an additional autologous plantaris tendon augmentation
      reached the highest primary stability (326 N +/- 124.9). CONCLUSIONS: The
      findings identify the Achilles tendon suture with a PDS-cord according to
      Bunnell's technique as a mechanically strong method. A plantaris tendon
      augmentation in addition to a PDS-thread can even add more stability to the
      Achilles tendon suture.

PMID- 17457598
TI  - Proximal humerus fractures: a comparative biomechanical analysis of intra and
      extramedullary implants.
AB  - INTRODUCTION: The biomechanical stability of a newly developed humerus nail
      (Sirustrade mark) for the treatment of fractures of the proximal humerus was
      analyzed in comparison to established systems. In total, three randomized groups
      were formed (n = 4 pairs) from 12 matched pairs of human cadaver humeri.
      MATERIALS AND METHODS: All intact bones were mechanically characterized by five
      subsequent load cycles under bending and torsional loading. The bending moment at
      the osteotomy was 7.5 N m the torsional moment was 8.3 N m over the hole specimen
      length. Loading was consistently initiated at the distal epiphysis and the
      deformation at the distal epiphysis was continuously recorded. Prior to implant
      reinforcement, a defect of 5 mm was created to simulate an unstable subcapital
      humerus fracture. For paired comparison, one humerus of each pair was stabilized
      with the Sirus proximal humerus nail while the counterpart was stabilized by a
      reference implant. In detail, the following groups were created: Sirus versus
      Proximal humerus nail (PHN) with spiral blade (group I); Sirus versus PHILOS
      plate (group II); Sirus versus 4.5 mm AO T-plate (group III). RESULTS: The Sirus
      nail demonstrated significantly higher stiffness values compared to the reference
      implants for both bending and torsional loading. The following distal epiphyseal
      displacements were recorded for a bending moment of 7.5 N m at the osteotomy:
      Sirus I: 8.8 mm, II: 8.4 mm, III: 7.7 mm (range 6.9-10.9), PHN 21.1 mm (range
      15.7-25.2) (P = 0.005), PHILOS plate 27.5 mm (range 21.6-35.8) (P < 0.001), 4.5
      AO T-plate 26.3 mm (range 24.3-33.9) (P = 0.01). The rotations corresponding to
      8.3 N m torsional moment were: Sirus I: 9.1 degrees , II: 9.3 degrees , III: 10.6
      degrees (range 7.5-12.2), PHN 13.5 degrees (range 10.3-15.6) (P = 0.158), PHILOS
      plate 15.6 degrees (range 13.7-20.8) (P = 0.007), 4.5 AO T-Platte 14.1 degrees
      (range 11.5-19.7) (P = 0.158). CONCLUSION: The intramedullary load carriers were
      biomechanically superior when compared to the plating systems in the fracture
      model presented here. Supplementary, the Sirus Nail showed higher stiffness
      values than the PHN. However, the latter are gaining in importance due to the
      possibility of minimal invasive implantation. Whether this will be associated
      with functional advantages requires further clinical investigation.

PMID- 17457599
TI  - Relevance of the low-affinity type of the Fcgamma-receptor IIIa-polymorphism in
      bullous pemphigoid.
AB  - Bullous pemphigoid (BP) is mediated by autoantibodies directed against molecules
      of the basement membrane zone. The biological function of antibodies involves
      binding to Fc-receptors expressed on human leucocytes. Recent studies suggested
      that a functional single-nucleotide-polymorphism of the Fcgamma-receptor IIIa
      (FcgammaRIIIa = CD16) at nucleotide 559 might predispose to the development of
      antibody-associated autoimmune disorders. This allelic difference affects the
      level of receptor affinity by predicting either a phenylalanine (F 158, low
      affinity) or valine (V 158, high-affinity). We investigated if inherited
      frequencies of the high- and low-affinity FcgammaRIIIa polymorphism differed
      between patients with BP and healthy subjects. Genomic DNA from peripheral white
      blood cells was analyzed regarding FcgammaRIIIa polymorphism at nucleotide 559 by
      an established polymerase chain reaction. Sixty-seven Caucasian patients with BP
      and 88 healthy controls were included into the study. There was no significant
      difference in the distribution of the homozygous high-affinity FcgammaRIIIa
      allotype (V/V) between BP-patients (14.9%) and healthy control subjects (20.5%).
      In contrast, 58.2% of the BP-patients were homozygous for the low-affinity
      FcgammaRIIIa-allotype (F/F), compared to 28.4% of the healthy controls (P =
      0.001, OR 3.51). The frequencies of the polymorphism in the control group were in
      range of formerly published frequencies for healthy Caucasian subjects. Thus, the
      FcgammaRIIIa (158 F/V) polymorphism may modulate the susceptibility to acquire
      BP.

PMID- 17457600
TI  - Two- versus three-dimensional ultrasound in the second and third trimester of
      pregnancy: impact on recognition and maternal-fetal bonding. A prospective pilot
      study.
AB  - OBJECTIVE: To assess the impact of three-dimensional (3D) versus two-dimensional
      (2D) ultrasound (US) on maternal-fetal bonding. STUDY DESIGN: Prospective
      randomized pilot study among low risk women with singleton fetuses in the second
      and third trimester. Dependent on the randomization pattern, US was commenced
      either with 2D US or 3D US and the effects were recorded with standardized
      questionnaires. RESULTS: Sixty patients were included. Although the quality of 2D
      US, assessed by the examinator, was superior to 3D US, maternal recognition was
      higher with 3-D US (P = 0.004). With 2D US, nulliparous patients had
      significantly more difficulties visualizing the fetus, than multiparous (P =
      0.03). However, the maternal preference of 3D US had no significant impact on
      maternal-fetal bonding. CONCLUSION: Ultrasound had no significant effect on
      maternal-fetal bonding. Three-dimensional images may facilitate recognition of
      the fetus, but 3D US did not have higher impact on maternal-fetal bonding. This
      finding may be a reason not to consider 3D ultrasound for routine scanning.

PMID- 17457601
TI  - Voice in early glottic cancer compared to benign voice pathology.
AB  - The purpose of this study is to compare (Dutch) Voice Handicap Index (VHIvumc)
      scores from a selected group of patients with voice problems after treatment for
      early glottic cancer with patients with benign voice disorders and subjects from
      the normal population. The study included a group of 35 patients with voice
      problems after treatment for early glottic cancer and a group of 197 patients
      with benign voice disorders. Furthermore, VHI scores were collected from 123
      subjects randomly chosen from the normal population. VHI reliability was high
      with high internal consistency and test-retest stability. VHI scores of glottic
      cancer patients were similar to those of patients with voice problems due to
      benign lesions. Both groups of patients were clearly deviant from the normal
      population. Within the normal population, 16% appeared to have not-normal voices.
      Based on ROC curves a cut-off score of 15 points was defined to identify patients
      with voice problems in daily life. A clinical relevant difference score of 10
      points was defined to be used for individual patients and of 15 points to be used
      in study designs with groups. Patients with voice problems after treatment for
      early glottic cancer encounter the same amount of problems in daily life as the
      other voice-impaired patients. The VHI proved to be an adequate tool for baseline
      and effectiveness measurement of voice.

PMID- 17457602
TI  - Perimetric and retrobulbar blood flow changes following carotid endarterectomy.
AB  - BACKGROUND: Carotid stenosis can produce visual changes. This study examines
      perimetric and retrobulbar blood flow changes following carotid endarterectomy
      (CEA) in patients without visual symptoms. METHODS: Sixteen patients (13 male,
      three female) with bilateral carotid stenosis were included. Patients with a
      history of ophthalmic disease, including glaucoma, were excluded. Peak systolic
      velocity (PSV) in the ophthalmic artery (OA), central retinal artery (CRA), and
      short posterior ciliary arteries (SPCAs) was measured preoperatively and 12
      months following CEA with color Doppler imaging (CDI), using a 7.5 MHz probe, at
      both the side operated upon and its fellow side. Automated static perimetry
      (Octopus 500 perimeter, G1x program) was performed at the same intervals. Mean
      sensitivity (MS), mean defect (MD), loss variance (LV) and corrected loss
      variance (CLV) were recorded. RESULTS: Preoperative PSV in the OA was
      significantly lower in the side operated on. Preoperative perimetric parameters
      were significantly compromised, compared with normative data, in both eyes.
      Postoperatively, PSV had significantly improved in all vessels examined in the
      carotid that was operated on, but only in the OA and SPCAs in the fellow side. MD
      had significantly improved postoperatively for both eyes, whereas improvement in
      the other perimetric parameters examined was not statistically significant.
      CONCLUSIONS: Perimetric changes occur in carotid stenosis. CEA results in the
      improvement of retrobulbar blood flow and perimetric parameters. Further research
      will be required to determine whether perimetric parameters may be used as
      additional indicators for carotid endarterectomy.

PMID- 17457603
TI  - Detection of disseminated tumor cells in the lymph nodes of colorectal cancer
      patients using a real-time polymerase chain reaction assay.
AB  - INTRODUCTION: Postoperative treatment for colorectal cancer depends on tumor
      stage as defined by the International Union Against Cancer (UICC). Adjuvant
      chemotherapy is not recommended in patients without lymph node involvement (UICC
      stages I and II). As many as 20-30% of these patients, however, will develop
      recurrence. AIMS AND OBJECTIVES: We conducted this study to determine the
      presence of disseminated tumor cells in the lymph nodes by quantitative real-time
      polymerase chain reaction (QRT-PCR) for cytokeratin 20 (CK20) in an attempt to
      provide supplementary information compared to histopathological findings.
      MATERIALS AND METHODS: Using a standard QRT-PCR assay, we examined primary tumors
      and 391 lymph nodes from 31 patients with completely resected colorectal cancer.
      RESULTS: Of the 31 primary tumors, 29 were positive for CK20 by QRT-PCR.
      DISCUSSION: An examination of the lymph nodes from the 29 patients with CK20
      positive primary tumors revealed that 35 (92.1% sensitivity) of the 38
      histopathologically positive lymph nodes and 54 (16.7%) of the 324
      histopathologically negative lymph nodes were positive by molecular analysis.
      CK20 expression was detected in 10 (100%) of 10 patients with a
      histopathologically positive lymph node status (pN1). In 9 (47.4%) of 19 patients
      with negative histopathological results (pN0), we detected a CK20 mRNA signal in
      at least one lymph node. Whereas eight patients with histopathologically negative
      lymph nodes could be upstaged on the basis of the molecular findings, no patient
      would be downstaged. CONCLUSION: Our results suggest that QRT-PCR for CK20 is a
      useful tool for the quantitative detection of micrometastases in the regional
      lymph nodes. We introduce a standardized procedure that integrates a molecular
      diagnostic technique in the clinical staging.

PMID- 17457604
TI  - Formation of syringyl-rich lignins in maize as influenced by feruloylated xylans
      and p-coumaroylated monolignols.
AB  - Grass cell walls are atypical because their xylans are acylated with ferulate and
      lignins are acylated with p-coumarate. To probe the role and interactions of
      these p-hydroxycinnamates during lignification, feruloylated primary cell walls
      isolated from maize cell suspensions were lignified with coniferyl and sinapyl
      alcohols and with varying levels of p-coumarate esters. Ferulate xylan esters
      enhanced the formation of wall-bound syringyl lignin more than methyl p
      coumarate, however, maximal concentrations of syringyl lignin were only one-third
      that of guaiacyl lignin. Including sinapyl p-coumarate, the presumed precursor of
      p-coumaroylated lignins, with monolignols unexpectedly accelerated peroxidase
      inactivation, interfered with ferulate copolymerization into lignin, and had
      minimal or adverse effects on cell wall lignification. Free phenolic groups of p
      coumarate esters in isolated maize lignin and pith cell walls did not undergo
      oxidative coupling with each other or with added monolignols. Thus, the extensive
      formation of syringyl-rich lignins and the functional role of extensive lignin
      acylation by p-coumarate in grasses remains a mystery.

PMID- 17457605
TI  - Effects of problem size, operation, and working-memory span on simple-arithmetic
      strategies: differences between children and adults?
AB  - Adult's simple-arithmetic strategy use depends on problem-related
      characteristics, such as problem size and operation, and on individual-difference
      variables, such as working-memory span. The current study investigates (a)
      whether the effects of problem size, operation, and working-memory span on
      children's simple-arithmetic strategy use are equal to those observed in adults,
      and (b) how these effects emerge and change across age. To this end, simple
      arithmetic performance measures and a working-memory span measure were obtained
      from 8-year-old, 10-year-old, and 12-year-old children. Results showed that the
      problem-size effect in children results from the same strategic performance
      differences as in adults (i.e., size-related differences in strategy selection,
      retrieval efficiency, and procedural efficiency). Operation-related effects in
      children were equal to those observed in adults as well, with more frequent
      retrieval use on multiplication, more efficient strategy execution in addition,
      and more pronounced changes in multiplication. Finally, the advantage of having a
      large working-memory span was also present in children. The differences and
      similarities across children's and adult's strategic performance and the
      relevance of arithmetic models are discussed.

PMID- 17457606
TI  - Expression of estrogen and progesterone receptors and inhibin-alpha in
      hepatobiliary cystadenoma: an immunohistochemical study.
AB  - To further characterize the immunohistochemical features of hepatobiliary
      cystadenoma with mesenchymal stroma, a battery of stains was performed on nine
      typical cases. All nine tumors had been resected from female patients who ranged
      in age from 30 to 59 years. Freshly cut sections were stained with antibodies to
      estrogen receptor (ER), progesterone receptor (PR), alpha-smooth muscle actin
      (SMA), inhibin-alpha, and cytokeratins (CK) 7, 8, 18, and 19. Nuclear staining of
      the mesenchymal stromal cells for ER and PR was present in all and seven out of
      nine cases, respectively. A strong cytoplasmic staining of the mesenchymal
      stromal cells for SMA was seen in all cases. A patchy pale cytoplasmic staining
      of the tumor epithelium for ER and PR was seen in five out of nine and four out
      of nine cases, respectively. Immunoreactivity of luteinized stromal cell for
      inhibin-alpha was documented in three out of nine cases. All tumors (nine out of
      nine) demonstrated strong cytoplasmic positivity of the epithelial lining of the
      cysts to CK7, CK8, CK18, and CK19, typical of biliary-type epithelium. The
      expression of ER, PR, and inhibin-alpha in the ovarian-like stroma supports the
      likely hormonal dependence of this tumor and probably explains its almost
      exclusive occurrence in women.

PMID- 17457607
TI  - CCR5 and CCR3 expression on T CD3+ lymphocytes from HIV/Leishmania co-infected
      subjects.
AB  - CC chemokine receptor 5 (CCR5) and CC chemokine receptor 3 (CCR3) are membrane
      bound proteins involved in HIV-1 entry into susceptible cells. All T lymphocyte
      subsets display CCR5 and CCR3 on their membrane surface. T helper 1 cells are
      known to express CCR5 but not CCR3, and most of T cells expressing CCR3 are T
      helper 2. This study aimed to assess the expression of CCR5 and CCR3 on
      peripheral blood CD3+ T lymphocytes of HIV-Leishmania co-infected individuals. A
      total of 36 subjects were enrolled; nine had HIV-Leishmania co-infection; nine
      were HIV-infected without Leishmania, nine had visceral leishmaniasis without HIV
      co-infection and nine were healthy blood donors. HIV-Leishmania co-infected
      subjects showed a significantly higher rate of CCR5+CD3+ T lymphocytes in
      comparison with the other studied groups. The higher rate of CD3+ T-cells
      expressing CCR5 found in HIV-Leishmania co-infected subjects may be related to
      the role of Leishmania as an enhancer of the progression to AIDS.

PMID- 17457608
TI  - Glutathione peroxidase, glutathione reductase and protein oxidation in patients
      with glioblastoma multiforme and transitional meningioma.
AB  - PURPOSE: The aim of this study was to assess glutathione peroxidase (GPx),
      glutathione reductase (GRx) and protein oxidation (POx) levels in patients with
      glioblastoma multiforme (GBM) and transitional meningioma (TM) and to compare
      with normal brain tissues. METHODS: GPx, GRx and POx levels were measured in 48
      brain tumors obtained during surgery and 15 normal brain tissues that were
      collected during autopsy. Results were compared between two groups. RESULTS: GPx
      and GRx activities were significantly lower in GBM and TM when compared to
      controls and the difference was statistically significant (P = 0.0001).
      Furthermore, the decrease in enzyme activities was more evident in GBM than in
      TM. In contrast, POx levels were found to be higher in both GBM and TM compared
      to controls and showed statistically significant difference (P = 0.00001).
      Increase in POx levels was clearer in GBM than TM. CONCLUSIONS: GPx and GRx
      decreased and POx increased significantly in both GBM and TM when compared to
      normal brain tissues. Further, clinical studies with a larger patient population
      are required to show the role(s) of antioxidant enzymes in brain tumors more
      accurately.

PMID- 17457609
TI  - Expression of estrogen receptor beta wt isoform (ERbeta1) and ERbetaDelta5 splice
      variant mRNAs in sporadic breast cancer.
AB  - PURPOSE: In addition to Estrogen Receptor alpha (ERalpha) and Progesterone
      Receptor (PR), the Second Estrogen Receptor (ERbeta) appears to play an important
      role not only in estrogen signaling, but also in the pathogenesis of cancer in
      estrogen dependent tissues. The existence of various isoforms and splice variants
      of both ERs additionally complicates elucidation of their physiological role and
      involvement in the process of carcinogenesis. METHODS: In this study, the
      expression of ERbeta1 mRNA (wild type of beta receptor) and splice variant
      ERbetaDelta5 mRNA (which codes for truncated protein) was measured by the
      quantitative RT-PCR (q RT-PCR) in the 60 samples of Breast Cancer (BC) and
      correlated with ERalpha and PR protein levels and with clinical and
      histopathological parameters. RESULTS: We found the inverse correlation of
      ERbetaDelta5 mRNA expression with the levels of PR and ERalpha proteins in the
      group of postmenopausal patients; we also report the lower expression of ERbeta1
      and ERbetaDelta5 mRNA in the larger tumors (>20 mm, T2, and T3) than in smaller
      ones (< or =20 mm, T1). The decrease of ERbetaDelta5 mRNA expression in larger
      tumors is found to arise from ER-positive breast carcinomas. In addition, the
      portion of tumors with concomitant high expression of both transcripts matches up
      the known percentage of tumors resistant to endocrine therapy in patients with
      different ER/PR status. CONCLUSIONS: As far as we know, this is the first study
      in which ERbetaDelta5 mRNA splice variant was quantified by real-time RT-PCR in
      the clinical samples of breast cancer tissue. Until now, the focus of clinical
      reports was the level of ERbeta1, ERbeta2, and ERbeta5 isoforms. The higher
      expression of ERbetaDelta5 mRNA is associated with the indicators of low
      biological aggressiveness of tumor (low tumor size within ER-positive status in
      our study) suggesting that the uncontrolled local tumor growth may occur as the
      expression of ERbetaDelta5 mRNA decreases in estrogen-dependent breast cancer.

PMID- 17457610
TI  - Anatomic wide hepatectomy for treatment of hepatocellular carcinoma.
AB  - PURPOSE: We aimed to clarify the prognostic impact of the anatomic extent of
      hepatic resection (Hr) related to the tumor hepatic involvement (H) on patients'
      survival in the treatment of hepatocellular carcinoma (HCC). METHOD: The 305
      patients with HCC who had undergone hepatectomy were analyzed retrospectively.
      The patients were classified into the anatomic wide hepatectomy (Hr > H
      hepatectomy, i.e. Hr was larger than H, n = 93) group and the other hepatectomies
      (Hr < or = H hepatectomy, i.e. Hr was equal to or smaller than H, n = 212) group.
      We compared the clinico-pathologic features between the two hepatectomy groups
      and the prognostic factors associated with postoperative HCC recurrence by using
      the Cox's proportional hazard model. RESULTS: After median follow-up duration of
      50 months (range 1-223 months), in Hr > H and Hr < or = H hepatectomy groups, the
      cumulative 3, 5, 10 year disease-free survival rates were 58.1, 44.6, 27.1% and
      49.2, 33.0, 14.6%, respectively (P = 0.043). The overall survival was not
      significantly different between the groups (P = 0.401). Multivariate analysis
      revealed that Hr > H hepatectomy was an independent favorable factor for disease
      free survival: the relative risk was 0.64 (95% confidence interval, 0.43-0.95; P
      = 0.026). CONCLUSION: Anatomic wide (Hr > H) hepatectomy is a favorable procedure
      of choice in HCC for possibly reducing the risk of postoperative recurrence.

PMID- 17457611
TI  - Comparative study of the impact of 3- versus 8-month neoadjuvant hormonal therapy
      on outcome of laparoscopic radical prostatectomy.
AB  - PURPOSE: To comparatively evaluate the effect of 3- versus 8-month neoadjuvant
      hormonal therapy (NHT) on laparoscopic radical prostatectomy (LRP) operative and
      postoperative parameters. METHODS: We evaluated 55 patients with clinically
      localized prostate cancer treated by 3-month (25 patients, group-1), 8-month NHT
      (19 patients, group-2) and non-neoadjuvant therapy (11 patients, group-3) before
      LRP. Serum PSA levels and prostate volume were measured and evaluated monthly
      before operation. The operative and postoperative parameters were recorded and
      compared in the three different groups. RESULTS: Transrectal ultrasound
      determined that prostate volume decreased 39.6% in group 1 and 35.4% in group 2
      after 3-month NHT and a further 34.4% in group 2 after 8-month NHT. The mean
      prostate volume was significantly smaller after 8-month than 3-month NHT in group
      2 (P < 0.05). Mean serum PSA decreased 97.8% in group 1 and 98.1% in group 2
      after 3-month NHT. A further 72.9% PSA decrease was determined after 8-month NHT
      in group 2. There were no significant differences in the three groups with
      respect to mean operative time, mean blood loss, transfusion rate, operative
      difficulty, catheterization time, hospital time and complication rate (P > 0.05,
      respectively). Positive margin rate was significantly lower in the 3- or 8-month
      NHT group than in the non-adjuvant group (P < 0.05, respectively). However, there
      was no significant difference between the 3- and 8-month groups with respect to
      positive margin rate (P > 0.05). CONCLUSIONS: The prolonged NHT (8-month) did not
      affect the operative or postoperative parameters. The LRP can be safely performed
      in patients after prolonged NHT. Prospective randomized studies are required to
      determine whether prolonged NHT reduces the risk of biochemical recurrence after
      LRP.

PMID- 17457612
TI  - Role of the 5' --> 3' exonuclease and Klenow fragment of Escherichia coli DNA
      polymerase I in base mismatch repair.
AB  - We have previously demonstrated that the Escherichia coli strain mutS DeltapolA
      had a higher rate of transition and minus frameshift mutations than mutS or
      DeltapolA strains. We argued that DNA polymerase I (PolI) corrects transition
      mismatches. PolI, encoded by the polA gene, possesses Klenow and 5' --> 3'
      exonuclease domains. In the present study, rates of mutation were found to be
      higher in Klenow-defective mutS strains and 5' --> 3' exonuclease-defective mutS
      strains than mutS or polA strains. The Klenow-defective or 5' --> 3' exonuclease
      defective mutS strains showed a marked increase in transition mutations. Sites of
      transition mutations in mutS, Klenow-defective mutS and 5' --> 3' exonuclease
      defective mutS strains are different. Thus, it is suggested that, in addition to
      mutS function, both the Klenow and 5' --> 3' exonuclease domains are involved in
      the decrease of transition mutations. Transition hot and warm spots in mutS+
      polA+ strains were found to differ from those in mutS and mutS DeltapolA strains.
      We thus argue that all the spontaneous transition mutations in the wild-type
      strain do not arise from transition mismatches left unrepaired by the MutS system
      or MutS PolI system.

PMID- 17457613
TI  - Mortality and cancer incidence in males with Y polysomy in Britain: a cohort
      study.
AB  - The mortality and cancer incidence risks among males with Y polysomy are unknown
      because there have been no large long-term cohort studies carried out of such
      men. We conducted a cohort study of 667 men diagnosed with the abnormality in
      Britain since 1959 to compare their mortality and cancer incidence rates with
      those of the general population. Sixty deaths occurred during follow-up to
      December 2005, twice the number expected from general population rates
      (standardised mortality ratio (SMR) = 2.0 (95% confidence interval (CI) 1.5
      2.6)). Significantly raised mortality was observed for diseases of the nervous
      system (SMR = 7.0, 95% CI: 2.3-16.4), circulatory system (SMR = 2.1, 95% CI: 1.3
      3.2), respiratory system (SMR = 4.0, 95% CI: 1.8-7.5), genitourinary system (SMR
      = 10.2, 95% CI: 1.2-36.9), and congenital anomalies (SMR = 11.9, 95% CI: 3.2
      30.5). Four of the five nervous system deaths were from epilepsy, the risk of
      death from this condition being more than 20-fold raised. The rates of cancer
      incidence and mortality among these men was not significantly different from
      those in the general population. This study provides evidence that mortality
      rates from several specific causes are raised among men with Y polysomy. The use
      of these data in genetic counselling should be cautious particularly for cases of
      Y polysomy that are detected prenatally. Further investigations are required to
      confirm these findings and to elucidate the possible role of genes on the Y
      chromosome in the aetiology of these causes of death.

PMID- 17457614
TI  - Extreme individual marker F(ST )values do not imply population-specific selection
      in humans: the NRG1 example.
AB  - Extreme population differentiation, as measured by the F(ST) value, has been
      suggested as an indicator of recent population-specific positive selection.
      Elevated F(ST) values indicating high differentiation between continental groups
      were previously reported on a linkage disequilibrium region in the Neuregulin 1
      gene, a gene which has been associated to schizophrenia. In the present study we
      show evidence that high F(ST) values may not necessarily imply the action of
      selection, in particular positive selection, neither globally nor regionally,
      using the example of the NRG1 gene.

PMID- 17457615
TI  - Complex chromosome 17p rearrangements associated with low-copy repeats in two
      patients with congenital anomalies.
AB  - Recent molecular cytogenetic data have shown that the constitution of complex
      chromosome rearrangements (CCRs) may be more complicated than previously thought.
      The complicated nature of these rearrangements challenges the accurate
      delineation of the chromosomal breakpoints and mechanisms involved. Here, we
      report a molecular cytogenetic analysis of two patients with congenital anomalies
      and unbalanced de novo CCRs involving chromosome 17p using high-resolution array
      based comparative genomic hybridization (array CGH) and fluorescent in situ
      hybridization (FISH). In the first patient, a 4-month-old boy with developmental
      delay, hypotonia, growth retardation, coronal synostosis, mild hypertelorism, and
      bilateral club feet, we found a duplication of the Charcot-Marie-Tooth disease
      type 1A and Smith-Magenis syndrome (SMS) chromosome regions, inverted insertion
      of the Miller-Dieker lissencephaly syndrome region into the SMS region, and two
      microdeletions including a terminal deletion of 17p. The latter, together with a
      duplication of 21q22.3-qter detected by array CGH, are likely the unbalanced
      product of a translocation t(17;21)(p13.3;q22.3). In the second patient, an 8
      year-old girl with mental retardation, short stature, microcephaly and mild
      dysmorphic features, we identified four submicroscopic interspersed 17p
      duplications. All 17 breakpoints were examined in detail by FISH analysis. We
      found that four of the breakpoints mapped within known low-copy repeats (LCRs),
      including LCR17pA, middle SMS-REP/LCR17pB block, and LCR17pC. Our findings
      suggest that the LCR burden in proximal 17p may have stimulated the formation of
      these CCRs and, thus, that genome architectural features such as LCRs may have
      been instrumental in the generation of these CCRs.

PMID- 17457616
TI  - Inducible lectins with galectin properties and human IL1alpha epitopes opsonize
      yeast during the inflammatory response of the ascidian Ciona intestinalis.
AB  - Studies on inducible ascidian lectins may shed light on the evolutionary
      emergence of cytokine functions. Here, we show that the levels of opsonins, with
      IL1alpha-epitopes, increase in Ciona intestinalis hemolymph as a response to an
      inflammatory stimulus and, in particular, to intratunic injection of
      lipopolysaccharide (LPS). The inflammatory agent promptly (within 4 h) enhances
      Ca(2+)-independent serum hemagglutinating and opsonizing activities, which are
      both inhibited by D-galactose and D-galactosides (alpha-lactose, N-acetyl-D
      lactosamine, thio-digalactoside), suggesting that anti-rabbit erythrocyte lectins
      with galectin properties are involved as opsonins. Inducible galectin molecules
      contain interleukin-1alpha (IL1alpha) epitopes, and their activities are
      specifically inhibited by anti-human recombinant IL1alpha antibody. Analysis by
      SDS-polyacrylamide gel electrophoresis has revealed that the density of the bands
      of several serum proteins increases within 4 h after LPS injection, correlated
      with the enhanced serum activity. Moreover, Western blot patterns demonstrate
      that several serum proteins (59, 37, 30, 23, 15 kDa) cross-react with the
      antibody as early as 4 h post-injection. Although we have not been able to
      establish whether, in adition to galectins, various types of D-galactose-specific
      lectins are contained in the serum, we show, for the first time in invertebrates,
      that galectin molecules with opsonic properties can be enhanced in response to a
      non-specific inflammatory stimulus, and that their release can be further
      stimulated by LPS. Finally, we reveal that multiple galectins share human
      IL1alpha epitopes, probably because of steric configuration and the
      oligomerization process.

PMID- 17457617
TI  - Dragonfly predators influence biomass and density of pond snails.
AB  - Studies in lakes show that fish and crayfish predators play an important role in
      determining the abundance of freshwater snails. In contrast, there are few
      studies of snails and their predators in shallow ponds and marshes. Ponds often
      lack fish and crayfish but have abundant insect populations. Here we present the
      results of field surveys, laboratory foraging trials, and an outdoor mesocosm
      experiment, testing the hypothesis that insects are important predators of
      pulmonate snails. In laboratory foraging trials, conducted with ten species of
      insects, most insect taxa consumed snails, and larval dragonflies were especially
      effective predators. The field surveys showed that dragonflies constitute the
      majority of the insect biomass in fishless ponds. More focused foraging trials
      evaluated the ability of the dragonflies Anax junius and Pantala hymenaea to prey
      upon different sizes and species of pulmonate snails (Helisoma trivolvis, Physa
      acuta, and Stagnicola elodes). Anax junius consumed all three species up to the
      maximum size tested. Pantala hymenaea consumed snails with a shell height of 3 mm
      and smaller, but did not kill larger snails. P. acuta were more vulnerable to
      predators than were H. trivolvis or S. elodes. In the mesocosm experiment,
      conducted with predator treatments of A. junius, P. hymenaea, and the hemipteran
      Belostoma flumineum, insect predators had a pronounced negative effect on snail
      biomass and density. A. junius and B. flumineum reduced biomass and density to a
      similar degree, and both reduced biomass more than did P. hymenaea. Predators did
      not have a strong effect on species composition. A model suggested that A. junius
      and P. hymenaea have the largest effects on snail biomass in the field. Given
      that both pulmonate snails and dragonfly nymphs are widespread and abundant in
      marshes and ponds, snail assemblages in these water bodies are likely regulated
      in large part by odonate predation.

PMID- 17457618
TI  - Immunotactoid glomerulonephritis in a child with HIV infection: a case report.
AB  - Renal disease is a common complication of human immunodeficiency virus (HIV)
      infection in adults. In children, however, HIV pathology of the gastrointestinal
      and respiratory tracts predominates, whereas renal disease is often an incidental
      finding. In this report, we describe a child with stage III HIV infection
      associated with immunotactoid glomerulonephritis (IT). The patient was referred
      for investigation of idiopathic nephrotic syndrome. Electron microscopy of his
      renal biopsy specimen revealed numerous electron-dense microtubular deposits,
      arranged in parallel fashion, consistent with a diagnosis of IT. He received
      highly active antiretroviral therapy (HAART) as well as corticosteroids and is
      currently in remission. To our knowledge, this is the first report of IT in a
      child.

PMID- 17457619
TI  - Nephrotic syndrome preceding psoriasis in children.
AB  - Nephrotic syndrome is considered to be a late complication of psoriasis, reported
      usually in adults and characterized by IgA nephropathy or focal segmental
      glomerulosclerosis. We report on four children in whom steroid-resistant
      nephrotic syndrome either preceded (n = 3), by 41-120 months, or occurred
      simultaneously (n = 1) with psoriasis; renal histology showed minimal change
      disease. Therapy with corticosteroids and cyclosporine resulted in remission of
      renal and cutaneous symptoms. Minimal change nephrotic syndrome and psoriasis
      might share similar mechanisms of pathogenesis involving cell-mediated immunity.

PMID- 17457620
TI  - Quercetin protects human mesothelial cells against exposure to peritoneal
      dialysis fluid.
AB  - During peritoneal dialysis, mesothelial cells have been shown to undergo severe
      damage due to continuous exposure to peritoneal dialysis fluid (PDF) with
      cytotoxic physicochemical properties. In this study, we investigated the
      cytoprotective role of the bioflavonoid Quercetin in the in vitro model of
      peritoneal dialysis. Immortalized human mesothelial cells (Met5A) were exposed
      either to regular growth medium or to standard acidic lactate-buffered PDF
      (Dianeal PD4) or to a more biocompatible lactate-bicarbonate-buffered PDF
      (Physioneal 40). Parallel cell cultures were supplemented with 200 microM
      Quercetin. Cytotoxicity was assessed qualitatively by morphologic assessment and
      quantitatively by the release of cytoplasmic lactate dehydrogenase and
      fluorescence-activated cell sorting (FACS). PDF exposure with bioincompatible
      Dianeal PD4 resulted in severe disruption of cell cultures and in significantly
      increased lactate dehydrogenase (LDH) release (p=0.0007 vs. control). Addition of
      200 microM Quercetin significantly decreased the LDH release (p=0.04 vs. "pure"
      Dianeal PD4 exposure), comparable to control exposure and to more biocompatible
      Physioneal 40 exposure (p=0.37) and resulted in marked preservation of cell
      culture monolayers and cellular viability as assessed by FACS. Introduction of
      cytoprotective agents such as Quercetin may represent an alternate approach to
      protect mesothelial cells from cytotoxicity of frequently used PDFs, comparably
      effective to the introduction of novel, more biocompatible, PDFs.

PMID- 17457621
TI  - Serum and urine fibronectin levels in children with vesicoureteral reflux.
AB  - The study objective was to assess serum and urine fibronectin (FN) levels in
      children with vesicoureteral reflux (VUR) depending on reflux grade and urine
      osmolality. The study group (1) consisted of 54 VUR children, median age 4.28
      (range 0.6-15) years: subgroup A, 19 children with grade II; subgroup B, 19 with
      grade III; and subgroup C, 16 with grade IV or V VUR. The control group (2)
      included 27 healthy children. The immunoenzymatic method enzyme immunoassay (EIA)
      was used to determine serum soluble and urine FN levels, with an osmometer to
      measure urinary osmolality. The median urine FN in VUR children was 224.1 (15.4
      3537) ng/mg creatinine (Cr), compared with the control group: 137.9 (20.3-670.6)
      ng/mg Cr (p<0.05), whereas median serum FN was 395.0 (13.0-779.9) ng/ml and 121.9
      (25-345.1) ng/ml (p<0.05), respectively. A detailed analysis showed that only in
      subgroup C was the level of urinary FN significantly higher than in the control
      group (p<0.01). However, serum concentration was elevated in all VUR children (A
      C) compared with controls (p<0.01). Reduced osmolality, below 800 mOsm/kg H2O,
      was observed in subgroup C. Negative correlation between urinary osmolality and
      urinary FN was found (r=-0.426, p < 0.01). In children with VUR, serum FN
      increased with reflux grade, whereas its urinary level was elevated only in grade
      IV and V reflux with impaired urine concentration.

PMID- 17457622
TI  - Responses of soil microbial catabolic diversity to arbuscular mycorrhizal
      inoculation and soil disinfection.
AB  - Although it is usually admitted that arbuscular mycorrhizal (AM) fungi are key
      components in soil bio-functioning, little is known on the response of microbial
      functional diversity to AM inoculation. The aims of the present study were to
      determine the influence of Glomus intraradices inoculum densities on plant growth
      and soil microflora functional diversity in autoclaved soil or non-disinfected
      soil. Microbial diversity of soil treatments was assessed by measuring the
      patterns of in situ catabolic potential of microbial communities. The soil
      disinfection increased sorghum growth, but lowered catabolic evenness (4.8)
      compared to that recorded in the non-disinfected soil (6.5). G. intraradices
      inoculation induced a higher plant growth in the autoclaved soil than in the non
      disinfected soil. This AM effect was positively related to inoculum density.
      Catabolic evenness and richness were positively correlated with the number of
      inoculated AM propagules in the autoclaved soil, but negatively correlated in the
      non-disinfected soil. In addition, after soil disinfection and AM inoculation,
      these microbial functionality indicators had higher values than in the autoclaved
      or in the non-disinfected soil without AM inoculation. These results are
      discussed in relation to the ecological influence of AM inoculation, with
      selected fungal strains and their associated microflora on native soil microbial
      activity.

PMID- 17457623
TI  - Reduction in pediatric invasive pneumococcal disease in the Basque Country and
      Navarre, Spain, after introduction of the heptavalent pneumococcal conjugate
      vaccine.
AB  - This study evaluated the incidence of invasive pneumococcal disease, identified
      the causal serotypes, and tracked the evolution of the antibiotic susceptibility
      of Streptococcus pneumoniae isolates in the regions of the Basque Country and
      Navarre, Spain, before and after the introduction of the heptavalent pneumococcal
      conjugate vaccine. The study included all children aged between birth and 5 years
      diagnosed with bacteremia, meningitis, or bacteremic pneumonia caused by
      pneumococci. By the second year after introduction of the heptavalent
      pneumococcal conjugate vaccine, compared with the period 1998-2001, the incidence
      of invasive disease decreased by 64.3% in children less than 12 months of age, by
      39.7% in children less than 24 months of age, and by 37.5% in children less than
      60 months of age. The prevalence of clinical isolates of S. pneumoniae that
      lacked susceptibility to penicillin decreased by 58.2% among children less than
      60 months of age. With an estimated coverage by four-dose heptavalent
      pneumococcal conjugate vaccine of 28-45% in 2003, the number of invasive
      pneumococcal infections in the Basque Country and in Navarre fell significantly
      after just 2 years of immunization, underscoring the importance of improving
      vaccination coverage under a universal childhood immunization program.

PMID- 17457624
TI  - Outcomes in 74 patients with an appendicolith who did not undergo surgery: is
      follow-up imaging necessary?
AB  - The objective of this study was to report the clinical outcome of patients with
      an appendicolith on computed tomography (CT) who did not undergo appendectomy on
      initial presentation. Reports from 45,901 abdominal CT examinations performed
      between March 2000-March 2004 containing the words "appendicolith" or "fecalith"
      were identified. Patients with appendicoliths not initially undergoing
      appendectomy were followed to assess re-presentation with abdominal pain
      ultimately requiring appendectomy. Seventy-four patients had an appendicolith on
      CT report, were discharged without surgery, and had clinical follow-up. Fifty-two
      of 74 (70%) patients had no appendiceal symptoms, were given an alternate
      diagnosis, and did not return with appendicitis. Twenty-two of 74 (30%) patients
      were discharged without acute appendicitis but with possible appendiceal
      symptoms. Five of these 22 (23%) patients returned with pathologically proven
      acute appendicitis, and all had possible appendiceal symptoms at initial
      presentation. An appendicolith may be a marker of increased risk for appendicitis
      but is not an indication for appendectomy.

PMID- 17457625
TI  - MDCT diagnosis of appendicitis using only coronal reformations.
AB  - The purpose of this study was to assess the feasibility of diagnosing
      appendicitis based on coronal reformations without the aid of transverse images.
      Abdominal and pelvic computed tomography (CT) scans of 53 patients (27 with
      appendicitis and 26 without appendicitis) were reviewed. All scans were obtained
      using a four-slice multi-detector row CT. The radiologists were not aware of the
      final diagnosis. Cases were reviewed for the visualization of the appendix and
      presence of appendicitis. All images were reviewed on picture archiving and
      communication systems. There were no false positives for diagnosing appendicitis
      when using either the transverse or coronal reformations. Appendicitis was not
      seen on the coronal images in one case, and there were no false negatives when
      transverse reformations alone were used. This difference was not statistically
      significant (p < 0.0001 for both modes of display). The sensitivity for
      diagnosing appendicitis based on the coronal images alone was 96%, the
      specificity was 100%, and the accuracy was 98%. Coronal reformations decreased
      the number of images reviewed by 19%. CT diagnosis of appendicitis based on the
      coronal images is accurate.

PMID- 17457626
TI  - Cyclophosphamide-induced agenesis of cerebral aqueduct resulting in hydrocephalus
      in mice.
AB  - The present work was undertaken to reveal the mechanism of cerebral aqueduct
      agenesis found to result in hydrocephalus following intrauterine exposure to
      model teratogen, cyclophosphamide, in murine fetuses. A single dose of 10-mg/kg
      body weight cyclophosphamide was injected intaperitoneally to pregnant mice on
      day 10, 11 or 12 of gestation. Fetuses were collected through abdominal incision
      on day 18 and studied for various malformations of brain and cranium including
      hydrocephalus. Incomplete development and failure of canalization of the cerebral
      aqueduct were detected when serial sections of brain in coronal and transverse
      planes were studied under the microscope. Biotechnological investigations such as
      % DNA fragmentation, % viable cell count and cell proliferation assay were
      carried out on brain cells for further studies. Agenesis and non-canalization of
      the cerebral aqueduct resulted in increased pressure of CSF, which led to rupture
      of the aqueduct complicated by leakage and accumulation of CSF in brain substance
      forming a cavity containing CSF parallel and lateral to the unopened part of the
      cerebral aqueduct. Incomplete development along with non-canalization of the
      cerebral aqueduct resulted in blockage of CSF flow through the ventricles that
      manifest as internal hydrocephalus. External hydrocephalus on the other hand was
      detected where the CSF accumulated in the cavity formed inside the brain
      substance and established communication with the CSF in the subarachnoid space.
      Cyclophosphamide induced inhibition of mitosis and cell differentiation of
      ependymal cells reflecting a decreased % viable cell count and cell proliferation
      assay along with augmentation of apoptosis of brain cells quantified as increased
      % DNA fragmentation count, which were identified as the contributing factors
      underlying the agenesis and incomplete development of the cerebral aqueduct. The
      study also suggests that cell survival, proliferation, migration or
      differentiation of ependymal cells might have been affected, and we speculate
      that CSF may have an inducing role in the development and canalization of the
      cerebral aqueduct.

PMID- 17457627
TI  - Aspects of eye accommodation evaluated by finite elements.
AB  - Axisymmetric nonlinear finite models of accommodation incorporating the
      posteriorly sloped force and vitreous effects have been studied by means of their
      effectiveness in mechanical and optical performances. All materials were assumed
      to be linearly elastic, vitreous and lens matrices were incompressible. The
      present model is subjected to certain indicated shortcomings, however, the
      behavior of the model is predictable, reasonable and favourably consistent with
      different published data, supporting the Helmholtz theory of accommodation.

PMID- 17457628
TI  - Genetic analysis of polyketide synthase and peptide synthetase genes in
      cyanobacteria as a mining tool for secondary metabolites.
AB  - Molecular screening using degenerate PCR to determine the presence of secondary
      metabolite genes in cyanobacteria was performed. This revealed 18 NRPS and 19 PKS
      genes in the 21 new cyanobacterial strains examined, representing three families
      of cyanobacteria (Nostocales, Chroococales and Oscillatoriales). A BLAST analysis
      shows that these genes have similarities to known cyanobacterial natural
      products. Analysis of the NRPS adenylation domain indicates the presence of novel
      features previously ascribed to both proteobacteria and cyanobacteria.
      Furthermore, binding-pocket predictions reveal diversity in the amino acids used
      during the biosynthesis of compounds. A similar analysis of the PKS ketosynthase
      domain shows significant structural diversity and their presence in both mixed
      modules with NRPS domains and individually as part of a PKS module. We have been
      able to classify the NRPS genes on the basis of their binding-pockets. Further,
      we show how this data can be used to begin to link structure to function by an
      analysis of the compounds Scyptolin A and Hofmannolin from Scytonema sp. PCC
      7110.

PMID- 17457629
TI  - Central serous chorioretinopathy and risk for obstructive sleep apnea.
AB  - Patients with obstructive sleep apnea (OSA), in comparison to controls, have
      increased levels of circulating epinephrine and norepinephrine, both of which are
      risk factors for the development of central serous chorioretinopathy (CSCR). The
      aim of this pilot study was to investigate the frequency of symptoms that suggest
      OSA in CSCR patients and normal controls. The Berlin Questionnaire, a validated
      research tool to assess risk for OSA, was administered to 29 patients who met the
      criteria for active, acute, non-steroid-induced CSCR and 29 controls matched for
      age and sex. In this retrospective case-controlled study, the main outcome
      measure was increased risk for OSA. The mean age of the patients was 47.8 years
      (range 29-72) and the mean age of controls was 47.3 years (range 25-70). Seventy
      six percent (22) of both groups were men. Survey scores showed 58.6% (17) of
      patients with CSCR to be at an increased risk for OSA compared to 31.0% (nine) of
      controls. A conditional logistic regression analysis showed that the CSCR group
      had a higher proportion with an increased risk for OSA compared to the control
      group (odds ratio=3.67; 95% CI: 1.02, 13.14; P = 0.046). Patients with CSCR may
      be more likely than other adults to have OSA, and screening for this sleep
      disorder should be considered in this population. Further research is warranted
      to determine whether sleep apnea may contribute to the development of CSCR, and
      to assess whether treatment of sleep apnea might offer a new therapeutic option
      for some patients with CSCR.

PMID- 17457630
TI  - Construct validity for the Health Utilities Index in a sleep center.
AB  - We utilized well-established and validated quality of life (QoL) measures to test
      the validity of the Health Utilities Index (HUI) in patients with untreated sleep
      disorders in a cross-sectional study. We submitted a 66-question survey to 86
      patients presenting to the University of Maryland Sleep Disorders Center (68 with
      sleep apnea, 18 with other sleep disorders). HUI mark 2 (HUI2) and HUI mark 3
      (HUI3) were compared with other indices of QoL: medical short form 12 (SF-12),
      Epworth Sleepiness Scale (ESS), and Functional Outcomes of Sleepiness
      Questionnaire (FOSQ). The participants of this study were eighty-six patients
      presenting with untreated sleep disorders to the University Medical Center. There
      were no interventions. The mean age in our patients was 50.7 +/- 14.2 years with
      a mean body mass index of 32.9 +/- 7.6. For patients with sleep apnea, the mean
      respiratory disturbance index was 32.6 +/- 29.1. For all patients, the mean HUI2
      score was 0.73 + 0.23, and the mean HUI3 score was 0.6 +/- 0.35 (p = 0.0066 for
      difference from HUI2). The mean SF-12 physical components (PC) score was 43.6 +/-
      12.1, and the mean SF-12 mental components (MC) score was 49.8 identical with
      40.1. The mean ESS score was 10.5 + 5.2, and the mean FOSQ score was 16.4 +/-
      3.5. Significant bivariate correlations were found between HUI2 and HUI3 as well
      as between both of these and age, SF-12, SF-12 PC score, ESS, and FOSQ. Stepwise
      multivariate regression revealed significant independent correlations between
      HUI2 and age, SF-12 PC and the FOSQ, and between HUI3, SF-12 PC, and the FOSQ.
      There were no differences in HUI scores between obstructive sleep apnea (OSA) and
      non-OSA patients: (1) HUI3 scores are lower than HUI2 scores, (2) both HUI2 and
      HUI3 are correlated with other indices of QoL in sleep patients, and (3) the HUI
      surveys should be considered in QoL and economic impact studies in patients with
      sleep disorders.

PMID- 17457631
TI  - Time- and dose-related effects of three 5-HT receptor ligands on the genioglossus
      activity in anesthetized and conscious rats.
AB  - Clinical trials in obstructive sleep apnea syndrome patients reported moderate
      effects of serotoninergic drugs on oropharyngeal apneas, although numerous
      specific 5-HT ligands highly modulate the genioglossus muscle (GG) activity in
      experiments performed in anesthetized animals. The purpose of this study was to
      investigate time- and dose-related effects of central and systemic injections of
      8-OHDPAT (5-HT1A agonist), SB224289 (5-HT1B antagonist), and DOI (5-HT2A/2C
      agonist) on the GG activity in anesthetized and conscious rats. Electromyographic
      recordings of the GG activity (GGemg) were analyzed after central and systemic
      injections of each drug in ketamine-xylazine anesthetized rats.
      Electroencephalograms (EEG), as well as neck and GG muscle activities (Nemg and
      GGemg), were recorded in 15 additional rats to analyze changes in sleep-wake
      states before and after systemic injection of the drugs. Central injections of 8
      OHDPAT and DOI in anesthetized rats induced clear dose-related increases in
      phasic and tonic GGemg activities, respectively. The time-responses were inferior
      to 30 min with 8-OHDPAT and over 50 min with DOI. Moderate increases in phasic
      GGemg activity were also observed after central, but not peripheral injection of
      SB and DOI. The total sleep time measured in conscious rats significantly
      decreased after systemic injections of DOI and 8-OHDPAT, although no change was
      observed in phasic or tonic GGemg activity. The dose- and time-responses of the
      DOI in anesthetized rat partly explain the lack of GGemg tonic change in
      conscious rat. The moderate effect on the GGemg phasic activity of peripheral 5
      HT1A ligand injection easily explains the lack of change in conscious rat. The
      serotonergic modulation of the respiratory component of the GGemg remains
      complex, but is highly sensitive to 5-HT1A receptors after central injection in
      rats under anesthesia. Forthcoming therapy in OSAS should be made of mixed
      profiled neurotransmitters and different routes of administration.

PMID- 17457632
TI  - Internists, epidemics, outbreaks, and bioterrorist attacks.

PMID- 17457633
TI  - Reduced selection for codon usage bias in Drosophila miranda.
AB  - Biased codon usage in many species results from a balance among mutation, weak
      selection, and genetic drift. Here I show that selection to maintain biased codon
      usage is reduced in Drosophila miranda relative to its ancestor. Analyses of
      mutation patterns in noncoding DNA suggest that the extent of this reduction
      cannot be explained by changes in mutation bias or by biased gene conversion. Low
      levels of variability in D. miranda relative to its sibling species, D.
      pseudoobscura, suggest that it has a much smaller effective population size.
      Reduced codon usage bias in D. miranda may thus result from the reduced efficacy
      of selection against newly arising mutations to unpreferred codons.

PMID- 17457634
TI  - Unique regulation of the Calvin cycle in the ultrasmall green alga Ostreococcus.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GapAB) and CP12 are two major players
      in controlling the inactivation of the Calvin cycle in land plants at night. GapB
      originated from a GapA gene duplication and differs from GapA by the presence of
      a specific C-terminal extension that was recruited from CP12. While GapA and CP12
      are assumed to be generally present in the Plantae (glaucophytes, red and green
      algae, and plants), up to now GapB was exclusively found in Streptophyta,
      including the enigmatic green alga Mesostigma viride. However, here we show that
      two closely related prasinophycean green algae, Ostreococcus tauri and
      Ostreococcus lucimarinus, also possess a GapB gene, while CP12 is missing. This
      remarkable finding either antedates the GapA/B gene duplication or indicates a
      lateral recruitment. Moreover, Ostreococcus is the first case where the crucial
      CP12 function may be completely replaced by GapB-mediated GapA/B aggregation.

PMID- 17457635
TI  - Variability of nuclear SSU-rDNA group introns within Septoria species:
      incongruence with host sequence phylogenies.
AB  - We report structural features and distribution patterns of 26 different group I
      introns located at three distinct nucleotide positions in nuclear small subunit
      ribosomal DNA (SSU-rDNA) of 10 Septoria and 4 other anamorphic species related to
      the teleomorphic genus Mycosphaerella. Secondary structure and sequence
      characteristics assigned the introns to the common IC1 and IE groups. Intron
      distribution patterns and phylogenetic relationships strongly suggested that some
      horizontal transfer events have occurred among the closely related fungal species
      sampled. To test this hypothesis, we used a comparative approach of intron- and
      rDNA-based phylogenies through MP- and ML-based topology tests. Our results
      showed two statistically well-supported major incongruences between the intron
      and the equivalent internal transcribed spacer (ITS) tree comparisons made. Such
      absence of a co-evolutive history between group I introns and host sequences is
      discussed relatively to the intron structures, the mechanisms of intron movement,
      and the biology of the Mycosphaerella pathogenic fungi.

PMID- 17457636
TI  - Indomethacin use for the management of patent ductus arteriosus in preterms: a
      web-based survey of practice attitudes among neonatal fellowship program
      directors in the United States.
AB  - The objective of this study was to determine whether neonatal-perinatal
      fellowship programs (NFTPs) in the United States vary in indomethacin use for the
      management of patent ductus arteriosus (PDA) in < or =28 week gestational age
      infants at birth. A 53-item web-based survey was sent to 84 NFTP directors who
      received prenotification, followed 2 weeks later by a reminder letter. A total of
      56 NFTP directors responded (67% maximum response rate). Wide variation exists in
      the maximum number of indomethacin courses used to close ductus, use of
      indomethacin for reopened PDA beyond 14 days, ductal closure definition,
      contraindications before consideration of indomethacin, interventions for
      contraindications, and reported ductal closer rate after each indomethacin
      course. Indomethacin therapy for symptomatic PDA and short course of indomethacin
      are common practices. Indomethacin use for the management of PDA in premature
      infants varies among NFTP directors. Practice attitudes may explain variations in
      ductal closure and ligation rates. Because practice variations may have
      implications for long-term outcome of vulnerable premature infants, studies
      relevant to the management of PDA in premature infants are needed.

PMID- 17457637
TI  - Stent angioplasty: an effective alternative in selected infants with critical
      native aortic coarctation.
AB  - Management of native aortic coarctation during early months of life poses
      therapeutic challenges, and there is no consensus among medical professionals
      regarding a management plan. Much can be argued about the benefits, limitations,
      and/or complications of transcatheter versus surgical intervention in such cases.
      Occasionally, the complexity of the lesions limits management options. Therefore,
      each patient requires individual management decisions because there is no one
      therapeutic plan that satisfies all patients. In this report, four critically ill
      infants who had complex native coarctation are presented. Surgical repair was not
      possible because of relative contraindications. The patients underwent
      transcatheter stent implantation (six procedures and seven stents) as a
      nondefinitive procedure with acceptable results. Three patients improved. One
      patient did not survive, mainly due to other major complications. Multiple
      reexpansions of the stents were carried out when indicated. After a mean follow
      up of 45 months (range, 41-49), the three survivors were doing fine and had
      gained an average weight of 9.7 kg (range, 6.6-13.3). At the time of reporting,
      the relative contraindications no longer exist and the final surgical repair can
      be carried out. Our experience suggests that in certain situations and in
      critically ill infants with complex form of coarctation, stent angioplasty can be
      used as a life-saving palliative procedure. Further reexpansions can be done when
      required. This may serve as a bridge to major surgical repair in the future.

PMID- 17457638
TI  - Antenatal diagnosis of aortico-left ventricular tunnel.

PMID- 17457639
TI  - Inorganic species distribution and microbial diversity within high Arctic
      cryptoendolithic habitats.
AB  - Cryptoendolithic habitats in the Canadian high Arctic are associated with a
      variety of microbial community assemblages, including cyanobacteria, algae, and
      fungi. These habitats were analyzed for the presence of metal ions by sequential
      extraction and evaluated for relationships between these and the various
      microorganisms found at each site using multivariate statistical methods.
      Cyanobacteria-dominated communities exist under higher pH conditions with
      elevated concentrations of calcium and magnesium, whereas communities dominated
      by fungi and algae are characterized by lower pH conditions and higher
      concentrations of iron, aluminum, and silicon in the overlying surfaces. These
      results suggest that the activity of the dominant microorganisms controls the pH
      of the surrounding environment, which in turn dictates rates of weathering or the
      possibility for surface crust formation, both ultimately deciding the structure
      of microbial diversity for each cryptoendolithic habitat.

PMID- 17457641
TI  - Civilian extraperitoneal rectal gunshot wounds: surgical management made simpler.
AB  - BACKGROUND: Rectal injuries are associated with significant morbidity and
      mortality. Controversy persists regarding routine presacral drainage, distal
      rectal washout (DRW), and primary repair of extraperitoneal rectal injuries. This
      retrospective review was performed to determine the outcome of rectal injuries in
      an urban trauma center with a high incidence of penetrating trauma where a non
      aggressive surgical approach to these injuries is practiced. METHODS: The records
      of all patients with a full-thickness penetrating rectal injury admitted to the
      Trauma Center at Groote Schuur Hospital over a 4-year period were reviewed. These
      were reviewed for demographics, injury mechanism and perioperative management,
      anatomical site of the rectal injury, associated intra-abdominal injuries and
      their management. Infectious complications and mortality were noted.
      Intraperitoneal rectal injuries were primarily repaired, with or without fecal
      diversion. Extraperitoneal rectal injuries were generally left untouched and a
      diverting colostomy was done. Presacral drainage and DRW were not routinely
      performed. RESULTS: Ninety-two patients with 118 rectal injuries [intraperitoneal
      (7), extraperitoneal (59), combined (26)] were identified. Only two
      extraperitoneal rectal injuries were repaired. None had presacral drainage.
      Eighty-six sigmoid loop colostomies were done. Two (2.2%) fistula, one
      rectocutaneous, and one rectovesical, were recorded. There were nine (9.9%)
      infectious complications: surgical site infection (4), buttock abscess (1),
      buttock necrosis (1), pubic ramus osteitis (1), septic arthritis (2). No
      perirectal sepsis occurred. CONCLUSIONS: Extraperitoneal rectal injuries due to
      low-velocity trauma can be safely managed by fecal diversion alone.

PMID- 17457642
TI  - Stapled transanal rectal resection (STARR) to reverse the anatomic disorders of
      pelvic floor dyssynergia.
AB  - Anterior rectocele and rectoanal intussusception are anatomic disorders related
      to excessive straining during defecation that usually manifest with symptoms of
      obstructive defecation. Stapled transanal rectal resection (STARR), a newly
      described surgical method for correcting these disorders, is considered a good
      alternative to the traditional transrectal approaches. The aim of the present
      study was to assess the early postoperative functional results of STARR. A total
      of 16 patients (13 female) were subjected to the STARR procedure during a period
      of 12 months. The presence of anatomic disorders of the anorectum was verified by
      dynamic defecography. Preoperative assessment also included colonic transit time,
      anal sphincter ultrasonography, and anorectal stationary manometry. Postoperative
      assessment included the same battery of tests. Altogether, 12 patients had
      rectoanal intussusception of > 2 cm and rectocele. In eight of them the anterior
      component of the rectocele was 2 to 4 cm, and in four it was > 4 cm. Four
      patients had a 1- to 2-cm internal intussusception and a rectocele of < 2 cm. All
      of them reported evacuation difficulties, but none had significant incontinence.
      Preoperative endoscopy did not reveal the presence of a solitary ulcer in any of
      the patients. All females had had normal vaginal deliveries, and four of them
      were multiparous. No complications were encountered postoperatively, and the need
      for analgesics was minimal. At defecography, rectoanal anatomy was seen to be
      restored in all patients. Obstructive defecation symptoms remained rather
      unaffected in seven, disappeared in three, and improved significantly in the
      remaining six patients. The seven failures showed anismus at manometry and had
      biofeedback treatment with satisfactory results in five of them. Failure of the
      operation and biofeedback sessions to treat symptoms in those two cases was
      attributed to coexisting enterocele, which had been missed preoperatively.
      Immediately after surgery, most of the patients complained of urgency and
      frequent small motions that resolved spontaneously within 3 to 5 weeks in all but
      two cases. STARR is a safe, well tolerated surgical procedure that effectively
      restores anatomy and function of the anorectum in patients with anterior mucosal
      prolapse and rectoanal intussusception. Additional biofeedback treatment is
      usually necessary for further functional improvement. Failure may be the result
      of other coexisting anatomic and functional abnormalities of the pelvic floor.

PMID- 17457643
TI  - Surgical management of intestinal malrotation in adults.
AB  - OBJECTIVE: The aim of this study was to review our experience with diagnosis and
      surgical management of intestinal malrotation in adult patients. PATIENTS AND
      METHODS: A retrospective review of the surgical outcome of adults with intestinal
      malrotation was performed. Twelve patients were observed and treated between July
      1996 and July 2006 (4 women and 8 men; the mean age of the patients was 28.5
      years). Surgical outcomes, including postoperative complications, deaths, and
      resolution of preoperative symptoms, were measured. RESULTS: A diagnosis of
      malrotation was made preoperatively in five patients by upper gastrointestinal
      contrast study, barium enema, or computed tomography scan. The anomaly was
      discovered incidentally at laparotomy in seven patients. All cases were proved to
      be malrotation intraoperatively. Nine patients underwent laparotomy and three
      underwent laparoscopic surgery (one converted to an open procedure). Follow-up
      ranged from 2 months to 118 months. Three patients had complications: one had
      wound infection, one had delayed gastric emptying, and one developed adhesive
      ileus. There were only two recurrences detected and one patient with recurrence
      required reoperation. No one died. CONCLUSIONS: Intestinal malrotation is a rare
      but important cause of abdominal pain in adults. It may present with chronic or
      acute symptoms. Laparotomy and laparoscopy are alternative and feasible
      techniques with low rates of complications for the treatment of intestinal
      malrotation in adults.

PMID- 17457644
TI  - Rhamnolipid produced from agroindustrial wastes enhances hydrocarbon
      biodegradation in contaminated soil.
AB  - A crude biosurfactant solution was produced by Pseudomonas aeruginosa growing on
      agroindustrial wastes as the substrate and used to study its effect on
      hydrocarbon biodegradation by the indigenous soil microflora under laboratory
      conditions. Two concentrations were studied at first and 1 mg of biosurfactant/g
      of soil showed to be the most efficient for the total petroleum hydrocarbon
      reduction, which reached 85% at the first 20 days in soil microcosms.
      Respirometric and microbial analyses showed that the biosurfactant added did not
      have toxic effects over the microbial population. The use of a biosurfactant for
      bioremediation has been limited because of its high cost production.
      Biosurfactants produced from cost-free by-products combines waste minimization
      with economic potential bioremediation process.

PMID- 17457645
TI  - Clinical and environmental Burkholderia strains: biofilm production and
      intracellular survival.
AB  - Bacteria belonging to the Burkholderia species are important pulmonary pathogens
      in cystic fibrosis (CF) patients. Their ability to establish chronic and
      sometimes fatal infections seems linked to the quorum sensing-regulated
      expression of virulence factors. We examined 23 Burkholderia isolates, 19
      obtained from CF patients and 4 from the environment, to evaluate their ability
      to form biofilm and to penetrate and replicate inside J774 macrophagic cells. Our
      results indicate that biofilm formation and intracellular survival are behavioral
      traits frequently expressed by Burkholderia strains isolated from CF patients.
      Successive isolates obtained from each of four chronically infected patients
      yielded bacteria consistently belonging to the same strain but showing increasing
      ability to replicate intracellularly and to produce biofilm, possibly due to in
      vivo bacterial microevolution driven by the selective lung environmental
      conditions. Protection against antimicrobials granted to burkholderiae by the
      expression of these two virulence factors might account for the frequent failures
      of antibiotic treatment in CF patients.

PMID- 17457646
TI  - High-level oxacillin and gentamycin resistance with reduced susceptibility to
      vancomycin in Staphylococcus aureus-carrying mecA and femA gene complex.
AB  - Staphylococcus aureus oxiva 10 and oxiva 14 strains clinically isolated from
      diabetic patients were resistant to gentamycin and oxacillin The minimal
      inhibitory concentrations (MICs) of oxacillin and gentamycin were 720 and >2048
      microg/mL, respectively, for oxiva 10 and 680 and 400 microg/mL. respectively,
      for oxiva 14; both strains carry mecA and femA genetic determinants in their
      genomes. In addition, both are vancomycin-intermediate Staphylococcus aureus
      (VISA) isolates. The addition of vancomycin led to significant decreases in
      oxacillin resistance of both oxiva 10 and oxiva 14 strains, whereas the addition
      of vancomycin to gentamycin plates showed a decrease in gentamycin resistance of
      non-high-level gentamycin-resistant (non-HLGR) oxiva 14 and indifference in
      gentamycin resistance in HLGR oxiva 10. Transmission electron microscopy of
      representative strains unveils a remarkable increase in the thickness of the cell
      wall, indicating that thickening of the cell wall is a common phenotype
      associated with vancomycin resistance in VISA isolates. The present study reports
      that the rate of synergism and synergistic effect in the combination vancomycin
      gentamycin vary according to the MICs of gentamycin.

PMID- 17457647
TI  - Production and regulation of lipase activity from Penicillium restrictum in
      submerged and solid-state fermentations.
AB  - Different carbon (C) sources, mainly carbohydrates and lipids, have been screened
      for their capacity to support growth and lipase production by Penicillium
      restrictum in submerged fermentation (SmF) and in solid-state fermentation (SSF).
      Completely different physiological behaviors were observed after the addition of
      easily (oleic acid and glucose) and complex (olive oil and starch) assimilable C
      sources to the liquid and solid media. Maximal lipolytic activities (12.1 U/mL
      and 17.4 U/g) by P. restrictum were obtained with olive oil in SmF and in SSF,
      respectively. Biomass levels in SmF (12.2-14.1 mg/mL) and SSF (7.0-8.0 mg/g) did
      not varied greatly with the distinct C sources used. High lipase production (12.3
      U/g) using glucose was only attained in SSF, perhaps due to the ability of this
      fermentation process to minimize catabolite repression.

PMID- 17457648
TI  - Prevalence of community-occurring extended spectrum beta-lactamase-producing
      Enterobacteriaceae in Brazil.
AB  - The occurrence of extended-spectrum-beta-lactamase (ESBL)-producing strains in
      the community was investigated in a private laboratory located in Juiz de Fora,
      Brazil. All enterobacterial isolates analysed were collected from urine of human
      patients between the years 2000 and 2002. ESBL production was confirmed by double
      disk screening, combination disk method, and Etest ESBL strip. The isoelectric
      point of each beta-lactamase was determined in the crude extracts from each
      isolate. Detection of ESBL genes was performed by polymerase chain reaction and
      the genetic relatedness of the isolates determined by pulsed-field gel
      electrophoresis (PFGE). Of the 1,481 isolates, 22 (12 Klebsiella pneumoniae, 7
      Escherichia coli, 1 Providencia stuartii, 1 Citrobacter freundii, and 1 Serratia
      marcescens) were identified as ESBL producers. The frequency of ESBL producers in
      the community was 1.48%. TEM-type enzymes were identified in 95.4% of the
      isolates, followed by the SHV type. Seven strains produced CTX-M-type enzymes.
      This study showed that strains producing multiple beta-lactamases are also
      present in community-acquired bacterial isolates. Multiple strains exhibiting
      identical PFGE genotypes were found in individual patients indicating a common
      source of acquisition.

PMID- 17457649
TI  - Long-term locoregional vascular morbidity after isolated limb perfusion and
      external-beam radiotherapy for soft tissue sarcoma of the extremity.
AB  - BACKGROUND: Isolated limb perfusion (ILP) with tumor necrosis factor alpha (TNF
      alpha) and melphalan, followed by delayed surgical resection and adjuvant
      external-beam radiotherapy is a limb salvage treatment strategy for locally
      advanced soft tissue sarcomas. The long-term vascular side effects of this
      combined procedure were evaluated. METHODS: Thirty-two patients were treated for
      a locally advanced sarcoma of the upper (n = 5) or lower limb (n = 27). All
      patients underwent a noninvasive vascular work-up. RESULTS: Five patients
      underwent a leg amputation, in two cases due to critical leg ischemia 10 years
      after ILP. With a median follow-up of 88 (range, 17-159) months, none of the
      patients with a salvaged lower leg (n = 22) experienced peripheral arterial
      occlusive disease. Ankle-brachial index (ABI) measurements in the involved leg
      (median, 1.02; range, .50-1.20) showed a significant decrease compared with the
      contralateral leg (median, 1.09; range, .91-1.36, P = .001). Pulsatility index
      (PI) was decreased in the treated leg in 17 of 22 patients at the femoral level
      (median, 6.30; range, 2.1-23.9 vs. median, 7.35; range, 4.8-21.9; P = .011) and
      in 19 of 20 patients at popliteal level (median, 8.35; range, 0-21.4 vs. median,
      10.95; range, 8.0-32.6; P < .0005). In patients with follow-up of >5 years, there
      was more often a decrease in ABI (P = .024) and PI at femoral level (P = .011).
      CONCLUSIONS: ILP followed by resection and external-beam radiotherapy can lead to
      major late vascular morbidity that requires amputation. Objective measurements
      show a time-related decrease of ABI and femoral PI in the treated extremity.

PMID- 17457651
TI  - A mathematical model of valveless pumping: a lumped model with time-dependent
      compliance, resistance, and inertia.
AB  - A new lumped model of flow driven by pumping without valves is presented,
      motivated by biomedical applications: the circulation of the human fetus before
      the development of the heart valves and mechanism of blood flow during the
      external cardiopulmonary resuscitation (CPR). The phenomenon of existence of a
      unidirectional net flow around a loop of tubing that consists of two different
      compliances is called valveless pumping. The lumped parameter model of valveless
      pumping in this paper is governed by the ordinary differential equations for
      pressure and flow, with time-dependent compliance, resistance, and inertia. This
      simple model can represent the essential features of valveless pumping we
      observed in earlier mathematical models and physical experiments of valveless
      pumping. We demonstrate that not only parameters of the driving function, such as
      frequency or amplitude, but also physical parameters, such as wall thickness and
      tube stiffness, are important in determining the direction and magnitude of a net
      flow. In this system, we report two new and interesting phenomena of valveless
      pumping: One is that the shifted peak frequency can be predicted by the pulsewave
      speed and the other is that time-dependent resistance is a crucial factor in
      generating valveless pumping. We also demonstrate that this lumped model can be
      extended to a one-dimensional flow model of valveless pumping and explain why a
      linear case, the case of the constant compliance, resistance, and inertia,
      generates almost zero net flow. This emphasizes that the nonlinearity of
      valveless pumping is also an important factor to generate a net flow in a closed
      loop model of valveless pumping.

PMID- 17457652
TI  - Bayesian inference for the spatio-temporal invasion of alien species.
AB  - In this paper we develop a Bayesian approach to parameter estimation in a
      stochastic spatio-temporal model of the spread of invasive species across a
      landscape. To date, statistical techniques, such as logistic and autologistic
      regression, have outstripped stochastic spatio-temporal models in their ability
      to handle large numbers of covariates. Here we seek to address this problem by
      making use of a range of covariates describing the bio-geographical features of
      the landscape. Relative to regression techniques, stochastic spatio-temporal
      models are more transparent in their representation of biological processes. They
      also explicitly model temporal change, and therefore do not require the
      assumption that the species' distribution (or other spatial pattern) has already
      reached equilibrium as is often the case with standard statistical approaches. In
      order to illustrate the use of such techniques we apply them to the analysis of
      data detailing the spread of an invasive plant, Heracleum mantegazzianum, across
      Britain in the 20th Century using geo-referenced covariate information describing
      local temperature, elevation and habitat type. The use of Markov chain Monte
      Carlo sampling within a Bayesian framework facilitates statistical assessments of
      differences in the suitability of different habitat classes for H.
      mantegazzianum, and enables predictions of future spread to account for
      parametric uncertainty and system variability. Our results show that ignoring
      such covariate information may lead to biased estimates of key processes and
      implausible predictions of future distributions.

PMID- 17457653
TI  - Mathematical model for spatial segregation of the Rho-family GTPases based on
      inhibitory crosstalk.
AB  - Cdc42, Rac, and Rho are small GTPases known to play a central role in signal
      transduction to the actin cytoskeleton. These proteins regulate cell motility, by
      affecting nucleation, uncapping, and depolymerization of actin filaments, and
      acto-myosin contractility. Studies of crosstalk and mutual feedbacks in these
      three proteins have led to a number of proposals for their interaction. At the
      same time, observations of the spatio-temporal dynamics of Rho-family proteins
      give evidence of spatial polarization and mutual exclusion between Cdc42/Rac and
      Rho. In this paper, we formulate a mathematical model to account for such
      observations, based on the known underlying biology of these proteins. We first
      investigate which of the crosstalk schemes proposed in the literature is
      consistent with observed dynamics, and then derive a simple model that can
      correctly describe these dynamics (assuming crosstalk is mediated via Rho GEFs).
      We show that cooperativity is an essential ingredient in the interactions of the
      proteins. The co-occurrence of a stable rest state with the possibility of fast
      spatial segregation can be related to bistability in a set of underlying ODEs in
      which the inactive forms of these proteins are fixed at a constant level. We show
      that the fast diffusion of the inactive forms is essential for stabilizing the
      transition fronts in the PDE formulation of the model, leading to robust spatial
      polarization, rather than traveling waves.

PMID- 17457654
TI  - A model of solute transport through stratum corneum using solute capture and
      release.
AB  - A one-dimensional model of solute transport through the stratum corneum is
      presented. Solute is assumed to diffuse through lipid bi-layers surrounding
      impermeable corneocytes. Transverse diffusion (perpendicular to the skin surface)
      through lipids separating adjacent corneocytes, is modeled in the usual way.
      Longitudinal diffusion (parallel to the skin surface) through lipids between
      corneocyte layers, is modeled as temporary trapping of solute, with subsequent
      release in the transverse direction. This leads to a linear equation for one
      dimensional transport in the transverse direction. The model involves an
      arbitrary function whose precise form is uncertain. For a specific choice of this
      function, closed form expressions for the Laplace transform of solute out-flux at
      the inner boundary, and for the time lag are obtained in the case that a constant
      solute concentration is maintained at the outer skin surface, with the inner
      boundary of the stratum corneum kept at zero concentration, and with the stratum
      corneum initially free of solute.

PMID- 17457655
TI  - Mathematical model of BCG immunotherapy in superficial bladder cancer.
AB  - Immunotherapy with Bacillus Calmette-Guerin (BCG)-an attenuated strain of
      Mycobacterium bovis (M. bovis) used for anti tuberculosis immunization-is a
      clinically established procedure for the treatment of superficial bladder cancer.
      However, the mode of action has not yet been fully elucidated, despite much
      extensive biological experience. The purpose of this paper is to develop a first
      mathematical model that describes tumor-immune interactions in the bladder as a
      result of BCG therapy. A mathematical analysis of the ODE model identifies
      multiple equilibrium points, their stability properties, and bifurcation points.
      Intriguing regimes of bistability are identified in which treatment has potential
      to result in a tumor-free equilibrium or a full-blown tumor depending only on
      initial conditions. Attention is given to estimating parameters and validating
      the model using published data taken from in vitro, mouse and human studies. The
      model makes clear that intensity of immunotherapy must be kept in limited bounds.
      While small treatment levels may fail to clear the tumor, a treatment that is too
      large can lead to an over-stimulated immune system having dangerous side effects
      for the patient.

PMID- 17457656
TI  - Propagation of fluctuations in biochemical systems, I: linear SSC networks.
AB  - We investigate the propagation of random fluctuations through biochemical
      networks in which the number of molecules of each species is large enough so that
      the concentrations are well modeled by differential equations. We study the
      effect of network topology on the emergent properties of the reaction system by
      characterizing the behavior of variance as fluctuations propagate down chains and
      studying the effect of side chains and feedback loops. We also investigate the
      asymptotic behavior of the system as one reaction becomes fast relative to the
      others.

PMID- 17457657
TI  - Socioeconomic impact of ankylosing spondylitis in Morocco.
AB  - The goal of this study was to determine the impact of ankylosing spondylitis (AS)
      on the socioeconomic well-being of Moroccan patients. One hundred (100)
      consecutive AS patients (71 men, 29 women) were included. The socioeconomic
      consequences were studied by measuring direct costs, indirect costs (consequences
      on work capacity), and intangible costs (social impact) of AS. The mean age at AS
      onset was 26.85 years +/- 11.71 (7-64). The mean disease duration of AS was 12.05
      years +/- 8.32 (0.5-39). Financial difficulties due to AS were observed in 82% of
      the patients. In 28% of them, these conditions explained a bad observance to
      treatments. In 14% of the cases, they led children to leave school to support
      their handicapped parents. Work disability occurred in 22.9% of initially
      employed patients. Withdrawal from work was correlated to bad social conditions
      at work, higher scores of Bath ankylosing spondylitis functional index (BASFI),
      and absence of adherence to a social security system. Sexual problems were
      present in 64.2% of the patients and were correlated to higher scores of BASFI.
      There were also disturbances in housekeeping (65.8%) and in leisure time
      activities (72.2%). Patients received a financial and a psychological familial
      support in, respectively, 66 and 87% of the cases. Despite the great familial
      support, Moroccan AS patients suffer from important socioeconomic consequences
      because of the illness, the bad socioeconomic conditions, the insufficiency of
      state help, and the social security problems.

PMID- 17457658
TI  - Hughes-Stovin syndrome: is it incomplete Behcet's? Report of two cases and review
      of the literature.
AB  - In this report, we described two male patients with Hughes-Stovin syndrome. The
      first patient was a 26-year-old male who initially presented with deep vein
      thrombosis (DVT) in the right lower limb followed shortly by hemoptysis.
      Pulmonary CT angiography revealed bilateral pulmonary artery aneurysms secondary
      to underlying pulmonary vasculitis. While the second case was a 16-year-old male
      patient who initially presented with generalized fits due to sagittal sinus
      thrombosis and later followed by DVT in the left lower limb. Pulmonary CT
      angiography showed small pulmonary artery aneurysms with thrombosis of peripheral
      pulmonary artery branches. Both patients were treated successfully with steroids
      and immunosuppressive therapy and showed clinical improvement.

PMID- 17457659
TI  - Chemogenomic analysis identifies geldanamycins as substrates and inhibitors of
      ABCB1.
AB  - PURPOSE: A prerequisite for geldanamycin (GA, NSC122750) to targeting heat shock
      protein 90 and inhibiting tumor growth is sufficient intracellular drug
      accumulation. We hypothesized that membrane transporters on tumor cells determine
      at least in part the response to GA analogues. MATERIALS AND METHODS: To
      facilitate a systematic study of chemosensitivity across a group of GA analogues
      with similar chemical structures, we correlated mRNA expression profiles of most
      known transporters with growth inhibitory potencies of compounds in 60 tumor cell
      lines (NCI-60). We subsequently validated the gene-drug correlations using
      cytotoxicity and transport assays. RESULTS: Geldanamycin analogues displayed a
      range of negative correlations coefficients with ABCB1 (MDR1, or P-glycoprotein)
      expression. Suppressing ABCB1 in multidrug resistant cells (NCI/ADR-RES and
      K562/DOX) and ABCB1-transfected cells (BC19) increased sensitivity to GA
      analogues, as expected for substrates. Moreover, ABCB1-mediated efflux of
      daunorubicin in K562/DOX cells could be blocked markedly by GA analogues in a
      dose-dependent fashion. The IC(50) values (half-maximum inhibition of
      daunorubicin efflux) were 5.5, 7.3 and 12 muM for macbecin II (NSC330500), 17-AAG
      (NSC330507) and GA, respectively. CONCLUSIONS: These observations demonstrate
      that GA analogues are substrates as well as inhibitors of ABCB1, suggesting that
      drug interactions between GA analogues and other agents that are ABCB1 substrates
      may occur via ABCB1 in normal or tumor cells.

PMID- 17457660
TI  - Increased erythropoietin elimination in fetal sheep following chronic phlebotomy.
AB  - PURPOSE: To determine by pharmacokinetic (PK) means the role of erythropoietin
      receptor (EPO-R) upregulation in fetuses on the elimination of erythropoietin
      (EPO). MATERIALS AND METHODS: Six fetal sheep were catheterized at a gestational
      age of 125-127 days and phlebotomized daily for 6 days. Paired tracer PK studies
      using recombinant human EPO (rHuEPO) were conducted in the sheep fetuses at
      baseline and post-phlebotomy, 7 days later. A PK model with Michaelis-Menten
      elimination was simultaneously fit to the PK data at baseline and post-phlebotomy
      for each fetus. RESULTS: Daily phlebotomies reduced the hemoglobin levels from
      baseline values of 10.8 (5%) (mean (C.V.)) g/dl to a nadir of 4.5 (17%) g/dl post
      phlebotomy. The endogenous EPO concentration rapidly increased after the first
      phlebotomy and remained elevated, although variable, thereafter. The Michaelis
      Menten maximal rHuEPO elimination rate parameter, V(max), was significantly
      greater post-phlebotomy than at baseline (p < 0.05), increasing 1.31 fold. The
      fetal baseline "linear" clearance at very low concentrations of rHuEPO was
      determined to be 117 ml/kg/h, similar to that determined in newborn sheep but 2-3
      fold higher than that determined in adult sheep. CONCLUSIONS: The observed
      increase in V(max) is consistent with an up-regulation of EPO-R due to a positive
      feedback resulting from the phlebotomy-induced anemia.

PMID- 17457661
TI  - Transdermal delivery of cytochrome C--A 12.4 kDa protein--across intact skin by
      constant-current iontophoresis.
AB  - PURPOSE: To demonstrate the transdermal iontophoretic delivery of a small (12.4
      kDa) protein across intact skin. MATERIALS AND METHODS: The iontophoretic
      transport of Cytochrome c (Cyt c) across porcine ear skin in vitro was
      investigated and quantified by HPLC. The effect of protein concentration (0.35
      and 0.7 mM), current density (0.15, 0.3 or 0.5 mA.cm(-2) applied for 8 h) and
      competing ions was evaluated. Co-iontophoresis of acetaminophen was employed to
      quantify the respective contributions of electromigration (EM) and electroosmosis
      (EO). RESULTS: The data confirmed the transdermal iontophoretic delivery of
      intact Cyt c. Electromigration was the principal transport mechanism, accounting
      for approximately 90% of delivery; correlation between EM flux and
      electrophoretic mobility was consistent with earlier results using small
      molecules. Modest EO inhibition was observed at 0.5 mA.cm(-2). Cumulative
      permeation at 0.3 and 0.5 mA.cm(-2) was significantly greater than that at 0.15
      mA.cm(-2); fluxes using 0.35 and 0.7 mM Cyt c in the absence of competing ions (J
      ( tot ) = 182.8 +/- 56.8 and 265.2 +/- 149.1 microg.cm(-2).h(-1), respectively)
      were statistically equivalent. Formulation in PBS (pH 8.2) confirmed the impact
      of competing charge carriers; inclusion of approximately 170 mM Na(+) resulted in
      a 3.9-fold decrease in total flux. CONCLUSIONS: Significant amounts (
      approximately 0.9 mg.cm(-2) over 8 h) of Cyt c were delivered non-invasively
      across intact skin by transdermal electrotransport.

PMID- 17457662
TI  - Confocal microscopy for the elucidation of mass transport mechanisms involved in
      protein release from lipid-based matrices.
AB  - PURPOSE: It was the aim of this study to identify the governing mechanisms during
      protein release from cylindrical lipid matrices by visualizing mass transport and
      correlating the data with in vitro dissolution testing. MATERIALS AND METHODS:
      Glyceryl trimyristate cylinders of 2 mm diameter, 2.2 mm height and 7 mg weight
      were manufactured by compression of a protein-lipid powder mixture prepared by a
      polyethylene glycol (PEG) co-lyophilization technique. BSA was fluorescence
      labeled and the distribution visualized and quantified at different stages of the
      release process by confocal microscopy in parallel to the quantification in the
      release buffer. The impact of matrix loading and protein molecular weight was
      assessed with the model proteins lysozyme, BSA, alcohol dehydrogenase and
      thyroglobulin. RESULTS: Buffer penetration and protein release occurred
      simultaneously from the outer regions of the cylinder progressing towards the
      center. Release from the top and bottom of the matrix was not negligible but much
      slower than penetration from the side, probably due to an oriented arrangement of
      lipid flakes during compression. The different quantification strategies were
      found to yield identical results. At 6% protein loading, buffer penetration was
      complete after 4 days, while only 60% of the protein was liberated in that time
      and release continued up to day 63. Protein release kinetics could be described
      using the power law equation M ( t ) /M ( infinity ) = kt ( n ) with an average
      time exponent n of 0.45 (+/-0.04) for loadings varying between 1 and 8%. A
      percolation threshold at 5% pure protein loading and 3-4% mixed loading (PEG and
      protein at a 1:1 mass ratio) could be identified. Release rate was found to
      decrease with increasing molecular weight. CONCLUSIONS: Protein release from
      lipid-based matrices is a purely diffusion controlled mechanism. Potential
      protein stabilization approaches should address the time span between complete
      buffer penetration of the matrix and 100% release of the remaining loading, which
      would be exposed to an aqueous environment before leaving the matrix.

PMID- 17457663
TI  - Natural products isolated from species of Halgerda bergh, 1880 (Mollusca:
      Nudibranchia) and their ecological and evolutionary implications.
AB  - Chemical investigations of five species of molluscan nudibranchs, Halgerda,
      collected from Australia and Japan were carried out. We identified a novel
      tryptophan derivative halgerdamine (1) along with the known compounds trigonellin
      (3), esmodil (4), zooanemonin (5), and C2-alpha-D-mannosylpyranosyl-L-tryptophan
      (2) from Halgerda aurantiomaculata. C2-alpha-D-mannosylpyranosyl-L-tryptophan (2)
      was previously thought to be a by-product of tryptophan metabolism exclusive to
      humans. The only other chordates reported to contain this compound are a number
      of ascidian species from New Caledonia and Australia including Atriolum robustum
      and Leptoclinides dubius. The occurrence of 2 in a mollusc has not been
      previously reported. Structure elucidation of 1 was achieved by using high-field
      2D NMR spectroscopy. No secondary metabolites were detected in extracts from five
      of the six other species studied, whereas Halgerda gunnessi contained mixtures of
      acylated tetrasaccharides. The compounds isolated from Halgerda are different
      from those found in the close sister taxon, Asteronotus. Specifically, species of
      Halgerda contain no terpenes, spirodysin, or bromophenols, as does Asteronotus.
      Furthermore, in contrast to other members of the Nudibranchia such as Chromodoris
      and Phyllidia, in which compound yields are quite high, several cryptic species
      of Halgerda seem to lack secondary metabolites, whereas the two highly
      conspicuous species yield mildly cytotoxic MeOH extracts. Our findings support
      recent hypotheses regarding progressive evolution of opisthobranchs. In
      particular, opisthobranchs have evolved to exploit a wider range of food and
      metabolites than did their ancestors, a demonstration of physiological
      innovation. Some species of Halgerda may not be chemically protected either via
      de novo synthesis or by sequestering particularly toxic compounds.

PMID- 17457664
TI  - Single molecule spectroscopy of poly 3-octyl-thiophene (P3OT).
AB  - We report on the spectroscopy of isolated chains of P3OT, in a highly dilute
      solution in the inert polymer host poly(methyl-methacrylate) (PMMA). This
      environment permits a detailed analysis of emission transitions in the 1.9-2.2 eV
      range by suppressing the formation of the lowest emitting-energy aggregated form
      of P3OT. Herein it is observed that the 1.9-2.2 eV band is in fact split into low
      (red) and high (blue) energy forms in a highly analogous situation to that found
      for the conjugated polymer MEH-PPV. Another focus of this work is an
      investigation of the interaction of singlet and triplet excitons in P3OT. The
      results indicate that, like in MEH-PPV, triplet excitons are highly efficient
      fluorescence quenchers for P3OT, strongly quenching the fluorescence of P3OT
      under even relatively low excitation intensities.

PMID- 17457665
TI  - A simple flow-injection spectrofluorimetric method for the determination of
      mercury.
AB  - A highly sensitive flow-injection spectrofluorimetric method is presented for the
      rapid and simple determination of Hg (II) in environmental and pharmaceutical
      samples. Murexide (ammonium purpurate) was used as the fluorescence reagent in
      the carrier stream. An emission peak of murexide, which is decreased linearly by
      addition of Hg (II), occurs at 435 nm in aqueous solution with excitation at 335
      nm. A linear calibration was obtained for 5-200 ng ml(-1) Hg (II) with the
      relative standard deviation 2.5% (n = 5) for a 20 microl injection volume Hg
      (II). The limit of the detection was 1 ng ml(-1) and the sampling rate was 80 h(
      1). No significant interference was found by the ions commonly found in the most
      environmental samples. The proposed method was successfully applied for the
      determination of trace mercury in real samples and the validation of the proposed
      methodology is provided.

PMID- 17457666
TI  - P300 cognitive evoked potentials before and after liver transplantation.
AB  - P300 cognitive evoked potentials have been shown to be effective for the
      assessment of mild hepatic encephalopathy but no investigations of their use with
      liver transplantation has been conducted. In this pilot study 12 subjects (7
      male, 5 female, average age 43.9-years-old) underwent recording of auditory and
      visual P300 cognitive evoked potentials prior to liver transplantation and again
      3-6 months subsequent to transplantation. Significant increases (p < 0.01) in
      P300 visual amplitude, as well as significant decreases in visual (p < 0.01) and
      auditory latencies (p < 0.01) were observed following transplantation. Auditory
      amplitudes increased but not to a statistically significant degree. P300
      cognitive evoked potentials may provide a useful tool for monitoring the cerebral
      status of liver transplantation patients if combined with established methods
      such as cognitive testing and EEG. Further research of their usage with these
      patients is warranted.

PMID- 17457667
TI  - Amplification of HSD17B1 has prognostic significance in postmenopausal breast
      cancer.
AB  - In situ synthesis of estrogens is believed to be of great importance for the
      progression of breast cancer. In postmenopausal women most estrogens are
      synthesized in peripheral hormone-target tissues from circulating precursor
      steroids, by the enzymes involved in formation of active estrogens. One of the
      enzymes involved in this process is 17beta-hydroxysteroid dehydrogenase (17beta
      HSD) type 1. This enzyme catalyzes the interconversion of estrone (E1) to the
      biologically more potent estradiol (E2). The gene coding for 17beta-HSD type 1
      (HSD17B1) is located at 17q12-21. The aim of this study was to investigate
      altered gene copy number of HSD17B1 in breast cancer. We used real-time PCR and
      examined 387 postmenopausal breast tumors for amplification of HSD17B1, and if an
      increased mRNA level of this enzyme is associated with amplification of the gene.
      We also investigated whether amplification of HSD17B1 has a prognostic value.
      There was a significant correlation between gene copy number of HSD17B1 and mRNA
      expression level (P = 0.00002). ER-positive patients with amplification of
      HSD17B1 showed lower breast cancer survival than patients without amplification
      (P = 0.025). Among ER-negative patients there was no significant correlation
      between increased gene copy number of HSD17B1 and prognosis. Furthermore, we
      found that amplification of the gene had prognostic significance in multivariate
      analysis adjusting for other clinicopathological variables.

PMID- 17457668
TI  - Controversies in preservation of ovary function and fertility in patients with
      breast cancer.
AB  - Improved treatment of breast cancer in premenopausal patients increased survival
      rates, but the therapy may influence fertility and ovarian function. Currently
      there is a big public and individual interest of breast cancer affected women in
      preservation of ovarian function and fertility. Chemotherapy induced amenorrhea
      (CIA) has many objective (osteoporosis, cardiovascular, urogenital atrophy,
      cognitive etc.) and subjective (hot flushes, sleep disturbances, change of mood
      etc.) consequences. In patients with breast cancer who wish to avoid a CIA and to
      preserve their fertility ovarian protection by GnRH agonists, cryopreservation of
      operative sampled ovarian tissue or obtained fertilized or non-fertilized eggs
      after stimulation and puncture or embryos after in vitro fertilization are
      technically possible. However there are no evidence-based recommendations for
      preservation of fertility or ovarian function in breast cancer patients. Except
      the cryopreservation of embryos all other procedures are experimental. It is also
      undefined who is going to carry the costs. Moreover, there are recent data that
      the reappearance of ovarian hormones may stimulate occult tumor cells in hormone
      sensitive breast cancer. Therefore it seems necessary to inform breast cancer
      patients about the possible negative effects of preservation of ovarian function.

PMID- 17457669
TI  - Risk of neoplastic transformation in asymptomatic radial scar. Analysis of 117
      cases.
AB  - BACKGROUND: Radial scar (RS) is a benign breast lesion but a variable percentage
      of cases are associated with atypical epithelial proliferations and cancer.
      Previous studies have shown that patient age and the size of RS are correlated to
      a potential neoplastic transformation. METHOD: We collected 117 asymptomatic
      patients with suspected RS following a mammogram, histologically confirmed. The
      clinical, pathological and immunophenotypical analysis is reported. The cases are
      subdivided into three different groups: (1) RS "Pure", without epithelial atypia;
      (2) RS associated with epithelial atypical hyperplasia; (3) RS with cancer.
      RESULTS: "Pure" RS was detected in 55 patients (47%); the mean age was 48.1 years
      and the mean size 0.94 cm. RS associated with atypical epithelial hyperplasia was
      identified in 25 cases (21%) with a mean age of 53.1 years and a mean size of
      0.98 cm. Carcinoma in RS was observed in 37 cases (32%); the mean age was 55.5
      years and the mean size was 1.16 cm. The mean age was statistically significant
      (P = 0.004) in separating RS with cancer from the two other RS groups. The size
      of RS was not sufficiently statistically significant (P = 0.2) to differentiate
      the risk. Atypical lesions and cancers showed a morphology and marker of low
      grade aggressiveness. CONCLUSION: RS seems to represent a natural model of
      carcinogenesis starting from a proliferative lesion in patients of less than 50
      years of age and developing into an atypical and later into a carcinomatous
      lesion. The fact that most carcinomas arising in RS are low grade also favors
      this hypothesis. All RS should be excised.

PMID- 17457670
TI  - Breast cancer subpopulation with high risk of internal mammary lymph nodes
      metastasis: analysis of 2,269 Chinese breast cancer patients treated with
      extended radical mastectomy.
AB  - PURPOSE: The selective treatment of internal mammary lymph nodes (IMNs) in breast
      cancer is controversial. The purpose of this research was to determine the
      subpopulation patients with high risk of internal mammary lymph nodes metastasis
      who received extended radical mastectomy without any preoperative treatment from
      1956 to 2003 in China. PATIENTS AND METHODS: 1,679 Chinese patients were
      underwent extended radical mastectomy (ERM) between 1956 and 2003. Four
      individual variables were selected (tumor site, tumor size, the number of ALNs
      involvement, patient age),then classified by following standards: tumor
      site(lateral, central, medial),tumor size(T1:<or=2 cm; T2:2 < T <or= 5 cm, T3:>5
      cm), ALNs(0,1-3,4-6, >or=7), age(<or=35 y, 36-50 y, >50 y). Chi-square and binary
      logistic regression were used to analysis relationship of these variable and
      IMMs. RESULTS: The four individual variables were significantly associated with
      IMNs metastasis using univariate analysis. However, three individual variables
      except for tumor size independently impact the IMNs metastasis using multivariate
      analysis. The incidence of IMNs metastasis in patients with 4-6 and >or=7
      positive ALNs was 28.1%, 41.5%. Within subgroup patients with medial tumor and
      positive ALNs, the incidence of IMNs metastasis was 23.6% for patients with 1-3
      positive ALNs, and 47.5% for 4-6 positive ALNs, 38.7% for patients with >or=7
      positive ALNs. The incidence of IMNs metastasis was 25.4% for patients with T3
      tumor and younger than 35 y. CONCLUSION: Patients with following conditions had
      high risk of IMNS metastasis: (1) patients with 4 or more positive ALNs. (2)
      patients with medial tumor and positive ALNs.(3) patients with T3 tumor and
      younger than 35 y. (4) patients with T2 tumor and positive ALNs.(5) patients with
      T2 tumor and medial tumor .The incidences of IMNS metastasis for those patients
      were more than 20%.

PMID- 17457671
TI  - The oncofetal Thomsen-Friedenreich carbohydrate antigen in cancer progression.
AB  - The oncofetal Thomsen-Friedenreich carbohydrate antigen (Galbeta1-3GalNAcalpha1
      Ser/Thr TF or T antigen) is a pan-carcinoma antigen highly expressed by about 90%
      of all human carcinomas. Its broad expression and high specificity in cancer have
      attracted many investigations into its potential use in cancer diagnosis and
      immunotherapy. Over the past few years increasing evidence suggests that the
      increased TF occurrence in cancer cells may be functionally important in cancer
      progression by allowing increased interaction/communication of the cells with
      endogenous carbohydrate-binding proteins (lectins), particularly the members of
      the galactoside-binding galectin family. This review focuses on the recent
      progress in understanding of the regulation and functional significance of
      increased TF occurrence in cancer progression and metastasis.

PMID- 17457672
TI  - Transplantation of foetal neural stem cells into the rat hippocampus during
      trimethyltin-induced neurodegeneration.
AB  - The present study investigates the survival and fate of neural stem
      cells/progenitor cells (NSC/NPCs) homografted into the hippocampus of rats
      treated with trimethyltin (TMT), a potent neurotoxicant considered a useful tool
      to obtain a well characterized model of neurodegeneration, to evaluate their
      possible role in the reparative mechanisms that accompany neurodegenerative
      events. NSC/NPCs expressing eGFP by lentivirus-mediated infection were
      stereotaxically grafted into the hippocampus of TMT-treated animals and controls.
      Two weeks after transplantation surviving NSC/NPCs were detectable in 60% of TMT
      treated animals and 30% of controls, while 30 days after transplantation only 40%
      of TMT-treated animals showed surviving grafted cells, which were undetectable in
      controls. At both times investigated, while grafted NSC/NPCs differentiated into
      neurons or astrocytes could be observed in addition to undifferentiated NSC/NPCs,
      we did not find evidence of structural integration of grafted cells into the main
      site of hippocampal lesion leading to appreciable repair.

PMID- 17457673
TI  - Hyperoxidized peroxiredoxins and glyceraldehyde-3-phosphate dehydrogenase
      immunoreactivity and protein levels are changed in the gerbil hippocampal CA1
      region after transient forebrain ischemia.
AB  - Oxidative stress is a major pathogenic event occurring in several brain disorders
      and is a major cause of brain damage due to ischemia/reperfusion. Thiol proteins
      are easily oxidized in cells exposed to reactive oxygen species (ROS). In the
      present study, we investigated transient ischemia-induced chronological changes
      in hyperoxidized peroxiredoxins (Prx-SO3) and glyceraldehyde-3-phosphate
      dehydrogenase (GAPDH-SO3) immunoreactivity and protein levels in the gerbil
      hippocampus induced by 5 min of transient forebrain ischemia. Weak Prx-SO3
      immunoreactivity is detected in the hippocampal CA1 region of the sham-operated
      group. Prx-SO3 immunoreactivity was significantly increased 12 h and 1 day after
      ischemia/reperfusion, and the immunoreactivity was decreased to the level of the
      sham-operated group 2 days after ischemia/reperfusion. Prx-SO3 immunoreactivity
      in the 4 days post-ischemia group was increased again, and the immunoreactivity
      was expressed in glial components for 5 days after ischemia/reperfusion. GAPDH
      SO3 immunoreactivity was highest in the CA1 region 1 day after
      ischemia/reperfusion, the immunoreactivity was decreased 2 days after
      ischemia/reperfusion. Four days after ischemia/reperfusion, GAPDH-SO3
      immunoreactivity increased again, and the immunoreactivity began to be expressed
      in glial components from 5 days after ischemia/reperfusion. Prx-SO3 and GAPDH-SO3
      protein levels in the ischemic CA1 region were also very high 12 h and 1 day
      after ischemia/reperfusion and returned to the level of the sham-operated group 3
      days after ischemia/reperfusion. Their protein levels were increased again 5 days
      after ischemia/reperfusion. In conclusion, Prx-SO3 and GAPDH-SO3 immunoreactivity
      and protein levels in the gerbil hippocampal CA1 region are significantly
      increased 12 h-24 h after ischemia/reperfusion and their immunoreactivity begins
      to be expressed in glial components from 4 or 5 days after ischemia/reperfusion.

PMID- 17457675
TI  - A multi-scale model of dendritic cell education and trafficking in the lung:
      implications for T cell polarization.
AB  - Health Sciences face a significant challenge in translating basic science data
      into improved understanding of innate and adaptive immunity. To improve
      understanding of the dynamic role of dendritic cells in the lung, a mathematical
      model was developed using a physiologically structured framework that explicitly
      accounts for functional heterogeneity. As sentinels of the immune system,
      dendritic cells play critical roles in coupling innate to adaptive immunity and
      produce an important immune regulatory cytokine: IL-12. The term IL-12 actually
      refers to the net bioactivity of three related proteins; IL12p40, IL12p70, and
      IL12(p40)2; assembled from two independent gene products: p35 and p40. The model
      for dendritic cell education and trafficking was created by incorporating five
      dimensions: chronological time, maturational age, p35 signal, p40 signal, and
      spatial location. The computational framework was calibrated to and validated
      against appropriate experimental studies. Using this validated model, I explore
      the impact of dynamic changes in the lung epithelium of IL-4, IFN-gamma, and PGE2
      on the dynamic ability of dendritic cells to polarize T cell subsets. In summary,
      this multi-scale model provides an essential aid in understanding the impact of a
      dynamically changing lung microenvironment on the ability of dendritic cells to
      orchestrate adaptive immunity.

PMID- 17457674
TI  - Cell-cell signaling in the neurovascular unit.
AB  - Historically, the neuron has been the conceptual focus for almost all of
      neuroscience research. In recent years, however, the concept of the neurovascular
      unit has emerged as a new paradigm for investigating both physiology and
      pathology in the CNS. This concept proposes that a purely neurocentric focus is
      not sufficient, and emphasizes that all cell types in the brain including
      neuronal, glial and vascular components, must be examined in an integrated
      context. Cell-cell signaling and coupling between these different compartments
      form the basis for normal function. Disordered signaling and perturbed coupling
      form the basis for dysfunction and disease. In this mini-review, we will survey
      four examples of this phenomenon: hemodynamic neurovascular coupling linking
      blood flow to brain activity; cellular communications that evoke the blood-brain
      barrier phenotype; parallel systems that underlie both neurogenesis and
      angiogenesis in the CNS; and finally, the potential exchange of trophic factors
      that may link neuronal, glial and vascular homeostasis.

PMID- 17457676
TI  - Relationship violence and psychological distress among low-income urban women.
AB  - In this paper, we examined the association between relationship violence and
      psychological distress among low-income urban women. Extending prior research, we
      considered the effects of relationship violence within the context of other
      chronic stressors that are common in the lives of these women. Using data from
      the Welfare, Children, and Families project (1999), a probability sample of 2,402
      low-income women with children living in low-income neighborhoods in Boston,
      Chicago, and San Antonio, we predicted psychological distress with multiple
      measures of relationship violence, a wide range of sociodemographic variables,
      and several chronic stressors. Our results show that relationship violence is
      associated with higher levels of economic hardship, neighborhood disorder, and
      household disrepair. We also find that relationship violence is associated with
      higher levels of psychological distress, net of these other chronic stressors.
      Finally, we observe that the effects of relationship violence do not vary
      according to the chronic stressors under study. Because the adverse effects of
      relationship violence are similar for women despite other adverse circumstances,
      interventions and treatment efforts focused exclusively on relationship violence
      may make a unique contribution to the psychological well-being of low-income
      urban women.

PMID- 17457677
TI  - Epidemiology of work-related injuries requiring hospitalization among sawmill
      workers in British Columbia, 1989-1997.
AB  - This study describes hospitalized injuries among workers in British Columbia
      lumber industry. Between April 1989 and December 1997, from the hospital records
      of 5,745 male sawmill workers were analyzed for the present study. Work
      relatedness was determined using either ICD-9 external cause of injury codes,
      which have a digit-indicating place of occurrence, or a payment field, which can
      identify workers compensation agency. Poisson regression models were used to
      analyze differences in hospitalization rates across race, job category, age
      group, and calendar year. The crude and adjusted rate ratios were calculated
      along with the 95% confidence intervals (CIs). During the follow-up period, there
      were 164 work related hospitalization resulting in a rate for work-related
      hospitalization of 5.38 per 1,000 person years. The higher rates by nature of
      injury were for dislocation, sprains & strains, open wounds, and fracture of
      upper limbs. During the study period, the higher rates of injury by causes were
      machinery related, falls, and struck against. In the multivariate models, there
      were no statistically significant relationship of injury risk with age and race.
      In respect to occupation, compared to foremen/supervisor, other sawmills' workers
      did not have significantly elevated risk of injury. The trend analyses found a
      significant negative trend (P = 0.004) of injury risk over the whole study
      period. Knowing the causes and nature of injury and their related risk factors
      are helpful to employers, compensation officials, and other stakeholders to
      target preventive measures.

PMID- 17457678
TI  - Microsatellite markers reveal spatial genetic structure of Tetranychus urticae
      (Acari: Tetranychidae) populations along a latitudinal gradient in Europe.
AB  - The genetic structure of populations of the two-spotted spider mite Tetranychus
      urticae was investigated along a south-north European transect spanning from
      southern France to The Netherlands. Mites were collected on Urtica dioica in 6
      sampling zones. Microsatellite variation at 5 loci revealed considerable genetic
      variation with an average heterozygozity of 0.49. Significant heterozygote
      deficiency was found in 7 populations out of the 18 samples analyzed and one of
      them was completely monomorphic. Tetranychus urticae populations show some level
      of genetic structuring. First, genetic differentiation between localities (F (ST)
      estimates) was significant for all comparisons. Second, the analysis of molecular
      variance, AMOVA, indicates that there is an effect, albeit low (9%), of the
      locality in accounting for allele frequency variance. Geographic distance emerges
      as a factor responsible for this genetic structure. The results are discussed in
      relation to the biological features of the species and the known patterns of
      migration. Related agronomical issues are addressed.

PMID- 17457679
TI  - Vanadate-induced cell death is dissociated from H2O2 generation.
AB  - Vanadium is an environmentally toxic metal with peculiar and sometimes
      contradictory cellular effects. It is insulin-mimetic, it can either stimulate
      cell growth or induce cell death, and it has both mutagenic and antineoplastic
      properties. However, the mechanisms involved in those effects are poorly
      understood. Several studies suggest that H(2)O(2) is involved in vanadate-induced
      cell death, but it is not known whether cellular sensitivity to vanadate is
      indeed related to H(2)O(2) generation. In the present study, the sensitivity of
      four cell lines from different origins (K562, K562-Lucena 1, MDCK, and Ma104) to
      vanadate and H(2)O(2) was evaluated and the production of H(2)O(2) by vanadate
      was analyzed by flow cytometry. We show that cell lines very resistant to
      H(2)O(2) (K562, K562-Lucena 1, and Ma104 cells) are much more sensitive to
      vanadate than MDCK, a cell line relatively susceptible to H(2)O(2), suggesting
      that vanadate-induced cytotoxicity is not directly related to H(2)O(2)
      responsiveness. In accordance, vanadate concentrations that reduced cellular
      viability to approximately 60-70% of the control (10 mumol/L) did not induce
      H(2)O(2) formation. A second hypothesis, that peroxovanadium (PV) compounds,
      produced once vanadate enters into the cells, are responsible for the
      cytotoxicity, was only partially confirmed because MDCK cells were resistant to
      both vanadate and PV compounds (10 micromol/L each). Therefore, our results
      suggest that vanadate toxicity occurs by two distinct pathways, one dependent on
      and one independent of H(2)O(2) production.

PMID- 17457680
TI  - Angiogenesis and chronic inflammation: cause or consequence?
AB  - Evidence has been gathered regarding the association between angiogenesis and
      inflammation in pathological situations. These two phenomena have long been
      coupled together in many chronic inflammatory disorders with distinct
      etiopathogenic origin, including psoriasis, rheumatoid arthritis, Crohn's
      disease, diabetes, and cancer. Lately, this concept has further been
      substantiated by the finding that several previously established non-inflammatory
      disorders, such as osteoarthritis and obesity, display both inflammation and
      angiogenesis in an exacerbated manner. In addition, the interplay between
      inflammatory cells, endothelial cells and fibroblasts in chronic inflammation
      sites, together with the fact that inflammation and angiogenesis can actually be
      triggered by the same molecular events, further strengthen this association.
      Therefore, elucidating the underlying cellular and molecular mechanisms that
      gather together the two processes is mandatory in order to understand their
      synergistic effect, and to develop new therapeutic approaches for the management
      of these disorders that cause a great deal of discomfort, disability, and in some
      cases death.

PMID- 17457681
TI  - Methane emission and heavy metals quantification from selected landfill areas in
      India.
AB  - In this study, an attempt has been made to study methane flux and quantification
      of heavy metals from Municipal Solid Waste (MSW) landfill areas of selected
      cities in India. During the period of study, the average value of methane flux
      was estimated from these landfill areas varied from 146-454 mg/m2/h. Methane
      emission from landfill is of serious environmental global concern as it accounts
      for approximately 15 percentages of current Greenhouse gas emissions. It has been
      estimated that methane emission, from landfill areas in the world, in next two
      decades would be same as that what is emitted from paddy fields presently.
      Besides, the estimation of methane flux, quantification of some heavy metals was
      conducted to analyse the suitability of using MSW as compost. The average values
      for metals were observed to be both within the range of USEPA and Indian
      standards for MSW disposal in landfill areas and to be used as compost
      respectively.

PMID- 17457682
TI  - An empirical study of estimating vehicle emissions under cordon and distance
      based road user charging in Leeds, UK.
AB  - This paper presents the impact of road user charging (RUC) on vehicle emissions
      through application of traffic assignment and pollutant emission models. It
      presents results of an analysis of five RUC schemes on vehicle emissions in
      Leeds, UK for 2005. The schemes were: a 3 pound sterling inner ring road cordon
      charge; a double cordon with a 2 pound sterling inner ring road and a 1 pound
      sterling outer ring road charge; and distance charges of 2, 10 and 20 p/km levied
      for travel within the outer cordon. Schemes were compared to a no charge option
      and results presented here. Emissions are significantly reduced within the inner
      cordon, whilst beyond the cordon, localised increases and decreases occur. The
      double cordon exhibits a similar but less marked pattern. Distance charging
      reduces city-wide emissions by 10% under a 2 p/km charge, 42-49% under a 10 p/km
      charge and 52-59% under a 20 p/km charge. The higher distance charges reduce
      emissions within the charge zone, and are also associated with elevated emissions
      outside the zone, but to a lesser extent than that observed for cordon charging.

PMID- 17457683
TI  - Performance of bioreactor landfill with waste mined from a dumpsite.
AB  - Emissions from landfills via leachate and gas are influenced by state and
      stability of the organic matter in the solid waste and the environmental
      conditions within the landfill. This paper describes a modified, ecologically
      sound waste treatment technique, where municipal solid waste is anaerobically
      treated in a lysimeter-scale landfill bioreactor with leachate recirculation to
      enhance organic degradation. The results demonstrate a substantial decrease in
      organic matter (BOD 99%, COD 88% and TOC 81%) and a clear decrease in nutrient
      concentrations especially ammonia (85%) over a period of 1 year with leachate
      recirculation.

PMID- 17457684
TI  - Alternative soil quality indices for evaluating the effect of intensive cropping,
      fertilisation and manuring for 31 years in the semi-arid soils of India.
AB  - Soil quality assessment provides a tool for evaluating the sustainability of
      alternative soil management practices. Our objective was to develop the most
      sensitive soil quality index for evaluating fertilizer, farm yard manure (FYM),
      and crop management practices on a semiarid Inceptisol in India. Soil indicators
      and crop yield data from a long-term (31 years) fertilizer, manure, and crop
      rotation (maize, wheat, cowpea, pearl millet) study at the Indian Agricultural
      Research Institute (IARI) near New Delhi were used. Plots receiving optimum NPK,
      super optimum NPK and optimum NPK + FYM had better values for all the parameters
      analyzed. Biological, chemical, and physical soil quality indicator data were
      transformed into scores (0 to 1) using both linear and non-linear scoring
      functions, and combined into soil quality indices using unscreened
      transformations, regression equation, or principal component analysis (PCA). Long
      term application of optimum inorganic fertilizers (NPK) resulted in higher soil
      quality ratings for all methods, although the highest values were obtained for
      treatment, which included FYM. Correlations between wheat (Triticum aestivum L.)
      yield and the various soil quality indices showed the best relationship (highest
      r) between yield and a PCA-derived SQI. Differences in SQI values suggest that
      the control (no NPK, no manure) and N only treatments were degrading, while soils
      receiving animal manure (FYM) or super optimum NPK fertilizer had the best soil
      quality, respectively. Lower ratings associated with the N only and NP treatments
      suggest that one of the most common soil management practices in India may not be
      sustainable. A framework for soil quality assessment is proposed.

PMID- 17457685
TI  - Distribution of heavy metals in surface water of Ranipet industrial area in Tamil
      Nadu, India.
AB  - Ranipet industrial area is about 120 km from Chennai on Chennai-Bangalore highway
      and is a chronic polluted area identified by Central Pollution Control Board of
      India. It is one of the biggest exporting centers of tanned leather in India. The
      total number of industries located in and around Ranipet town are 240 tanneries
      along with ceramic, refractory, boiler auxiliaries plant, and chromium chemicals.
      Studies were carried out to find out the contamination of surface water bodies
      due to industrial effluents. The results reveal that the surface water in the
      area is highly contaminated showing very high concentrations of some of the
      heavy/toxic metals like Cadmium ranging from 0.2 to 401.4 microg/l (average of
      51.1 microg/l), Chromium 2.4-1,308.6 (average of 247.2 microg/l), Copper 2.1
      535.5 microg/l (average of 95.5 microg/l), Nickel 1.6-147.0 microg/l (average of
      36.7 microg/l), Lead 6.4-2,034.4 microg/l (average of 467.8 microg/l) and Zinc
      20.8-12,718.0 microg/l (average of 3,760.4 microg/l). The concentration levels of
      these metals are much above the permissible limits in surface water and are
      health hazards especially for the people working in the tannery industries. It
      was observed that the people in the area are seriously affected and suffering
      from occupational diseases such as asthma, chromium ulcers and skin diseases.
      Distribution of metals, their contents at different locations, and their effects
      on human health are discussed in this paper.

PMID- 17457686
TI  - Delimitation of arsenic-contaminated groundwater using risk-based indicator
      approaches around blackfoot disease hyperendemic areas of southern Taiwan.
AB  - This work determined scopes of arsenic(As)-contaminated groundwater using risk
      based indicator classification approaches in blackfoot disease hyperendemic areas
      of southern Taiwan. Indicator kriging was first used to establish a conditional
      cumulative distribution function at each cell. Three approaches--the p-quantile
      estimate, the E-type estimate and the minimization of the expected loss--were
      then adopted to delimit contaminated regions for a regulated standard of As
      concentrations in groundwater. According to a risk assessment model established
      in our previous research, the standard was set to 250 microg/l for aquacultural
      use, corresponding to the 77.1th percentile of observed concentrations.
      Misclassification risks and uncertainty were examined for the classification
      approaches. The analyzed results reveal that contaminated areas are the largest
      using the 0.771-quantile estimate, whereas they are the smallest using the
      minimization of the expected loss. Proportions of credible polluted areas with
      low risks to false positives maintain a constant, 12.9-13.2%, for the
      classification approaches. To reduce a great impact on human health, As-polluted
      groundwater should be strictly prohibited to cultivate fish in credible polluted
      zones and monitored persistently in polluted zones with high risks to false
      positives.

PMID- 17457687
TI  - Pharmacokinetic disposition of triclabendazole in cattle and sheep;
      discrimination of the order and the rate of the absorption process of its active
      metabolite triclabendazole sulfoxide.
AB  - A comparative pharmacokinetic study was conducted to determine the order and the
      rate of absorption of triclabendazole (TCBZ) in cattle and sheep. A commercial
      suspension of TCBZ (Biofasiolex, Biogenesis S.A., Argentina) was administered at
      a dose rate of 10 mg/kg by the oral route to six Holstein female calves and six
      Corriedale female sheep. The plasma concentration profiles of the metabolites
      triclabendazole sulfoxide (TCBZ-SO) and triclabendazole sulfone (TCBZ-SO(2)) were
      analysed by means of the non-compartmental method. The order of the absorption
      process of the active metabolite, TCBZ-SO, was determined by construction of
      curves of cumulative absorbed fraction of the drug by means of the Wagner-Nelson
      method. The appearance of TCBZ-SO in plasma of cattle and sheep resembles the
      entry of a constant quantity of drug into the organism per unit time. This is
      explained by the reservoir effect of the rumen, which acts as a biological slow
      release system for TCBZ-SO and its precursor TCBZ to the posterior digestive
      tract where they are absorbed. The plasma concentration profiles of TCBZ-SO in
      both species were well described by a one-compartment open model with zero-order
      process of absorption and first-order process of elimination. The values of AUC(0
      infinity) and C(max) of TCBZ-SO did not differ between species, while other
      kinetic parameters except for lambda(z) had higher values in calves than in
      sheep. In the case of TCBZ-SO(2), t(max) was the only parameter that did not
      differ between species, while other kinetic parameters except for lambda(z) had
      higher values in calves than in sheep.

PMID- 17457688
TI  - Brain natriuretic peptide and P wave duration in dialysis patients.
AB  - OBJECTIVES: P wave duration and dispersion, defined as the difference between the
      maximum and minimum P duration, are regarded as very important non-invasive ECG
      markers for assessing atrial arrhythmia risk. Plasma brain natriuretic peptide
      (BNP) level is an independent predictor of recurrence of atrial fibrillation. We
      compared the effects of hemodialysis (HD) and continuous ambulatory peritoneal
      dialysis (CAPD) on P wave duration, P dispersion, and BNP in end-stage renal
      disease (ESRD) patients and examined the relationship between BNP levels, P wave
      duration, and P dispersion. DESIGN AND METHODS: Age-matched 22 HD patients (mean
      age 52.3 +/- 14.0 years) and 19 CAPD patients (mean age 46.7 +/- 10.9 years) were
      studied. RESULTS: BNP levels were greater in HD patients before the HD session
      (459.0 +/- 465.1 pg mL(-1)) than in CAPD patients (139.0 +/- 170.1 pg mL(-1)).
      The maximum and minimum P duration, and P dispersion, were similar for both
      groups (P > 0.05). Whereas BNP levels were negatively related to minimum P
      duration (r = -0.518, P = 0.019), BNP levels were positively correlated with
      systolic blood pressure and diastolic blood pressure (r = 0.672, P = 0.001 and r
      = 0.497, P = 0.022, respectively) in HD patients. CONCLUSIONS: Whereas BNP levels
      are higher in HD patients when they are at peak-volume status, just before HD, P
      wave duration and P dispersion were similar for both groups. A negative
      relationship was detected between BNP levels and minimum P duration in HD
      patients. Expansion of extra-cellular volume causing myocardial stretching may be
      the principal cause of increased BNP in HD patients. A functional relationship
      between BNP and the P wave was not found. Additional studies are needed to
      evaluate the effect of BNP on the P wave.

PMID- 17457689
TI  - Comparison of hospital pharmacy practice in France and Canada: can different
      practice perspectives complement each other?
AB  - OBJECTIVE: To compare hospital pharmacy practice in France and Canada by
      identifying similarities and differences in the two institution's pharmacy
      activities, resources, drug dispensing processes and responsibilities. SETTING:
      Centre hospitalier universitaire Sainte-Justine (SJ), Montreal, Quebec, Canada
      and Hopital Robert Debre (RD), Paris, France, are two maternal-child teaching
      hospitals. They share a similar mission focused on patient care, teaching and
      research. METHOD: The data were gathered from annual reports, department
      strategic plans and by direct observation. MAIN OUTCOME MEASURE: The description
      and comparison of the legal environment, hospital demographics, pharmacy
      department data, drug dispensing processes and pharmacist activities in the two
      institutions. RESULTS: The Centre hospitalier universitaire Sainte-Justine and
      Hopital Robert Debre are similar with respect to their mission and general
      demographics; number of beds, annual hospital expenditures, number of admissions,
      visits and childbirths. The respective pharmacy departments differ in allocated
      resources. The main operational differences concern compounding, quality control
      programs and clinical activities. The French department also manages medical
      devices, medical gases, blood derivatives and the sterilisation unit. These
      comparisons highlight the more patient-oriented Canadian hospital pharmacy
      practice against the more product-oriented French hospital practice Factors
      contributing to these differences include academic curriculum, the attention paid
      to the legal environment by professional bodies, staffing patterns and culture.
      CONCLUSION: There are differences between the hospital pharmacy practice in the
      studied hospitals in Canada and France. Hospital pharmacy practice in France
      seems to be more product oriented, and the practice in Canada seems more patient
      oriented.

PMID- 17457690
TI  - Heliobacterial photosynthesis.
AB  - Heliobacteria contain Type I reaction centers (RCs) and a homodimeric core, but
      unlike green sulfur bacteria, they do not contain an extended antenna system.
      Given their simplicity, the heliobacterial RC (HbRC) should be ideal for the
      study of a prototypical homodimeric RC. However, there exist enormous gaps in our
      knowledge, particularly with regard to the nature of the secondary and tertiary
      electron acceptors. To paraphrase S. Neerken and J. Amesz (2001 Biochim Biophys
      Acta 1507:278-290): with the sole exception of primary charge separation, little
      progress has been made in recent years on the HbRC, either with respect to the
      polypeptide composition, or the nature of the electron acceptor chain, or the
      kinetics of forward and backward electron transfer. This situation, however, has
      changed. First, the low molecular mass polypeptide that contains the terminal FA
      and FB iron-sulfur clusters has been identified. The change in the lifetime of
      the flash-induced kinetics from 75 ms to 15 ms on its removal shows that the
      former arises from the P798+ [FA/FB]- recombination, and the latter from P798+ FX
      recombination. Second, FX has been identified in HbRC cores by EPR and Mossbauer
      spectroscopy, and shown to be a [4Fe-4S]1+,2+ cluster with a ground spin state of
      S=3/2. Since all of the iron in HbRC cores is in the FX cluster, a ratio of
      approximately 22 Bchl g/P798 could be calculated from chemical assays of non-heme
      iron and Bchl g. Third, the N-terminal amino acid sequence of the FA/FB
      containing polypeptide led to the identification and cloning of its gene. The
      expressed protein can be rebound to isolated HbRC cores, thereby regaining both
      the 75 ms kinetic phase resulting from P798+ [FA/FB]- recombination and the light
      induced EPR resonances of FA- and FB-. The gene was named 'pshB' and the protein
      'PshB' in keeping with the accepted nomenclature for Type I RCs. This article
      reviews the current state of knowledge on the structure and function of the HbRC.

PMID- 17457691
TI  - Structural basis for the mechanism of electron bifurcation at the quinol
      oxidation site of the cytochrome bc1 complex.
AB  - At the heart of the Q cycle hypothesis, the cytochrome bc1 complex (bc1) is
      required to separate the two electrons from a quinol molecule at the quinol
      oxidation site. Recent studies have brought to light an intricate mechanism for
      this bifurcated electron transfer. A survey of the protein data bank shows 30
      entries for the structures of bc1 and the homologous b6 f complex. These
      structures provide considerable insights into the structural organization of
      mitochondrial, bacterial, and plant enzymes. Crystallographic binding studies of
      bc1 with either quinone reduction (QN) and/or quinol oxidation (QP) site
      inhibitors offer atomic details on how these compounds interact with residues at
      their respective sites. Most importantly, the different locations and apparent
      flexibility observed in crystals for the extrinsic domain of the iron-sulfur
      protein (ISP) subunit suggest a mechanism for electron bifurcation at the QP
      site. Analyses of various inhibitor-bound structures revealed two classes of QP
      site inhibitors: Pm inhibitors that promote ISP mobility and Pf inhibitors that
      favor the fixation of the ISP conformation. Those analyses also shed light on a
      possible process by which the ISP motion switch is controlled. The first phase
      reduction of ISP is shown to be comparable to the reduction of the bL heme by pre
      steady state kinetic analysis, whereas the second phase reduction of ISP share
      similar kinetics with the reduction of the bH heme. The reduction of cyt c1 is
      measured much slower, indicating that the reduced ISP remains bound at the QP
      site until the reduced heme bL is oxidized by the heme bH and supporting the
      existence of a control mechanism for the ISP motion switch.

PMID- 17457692
TI  - Regionally selective decreases in cerebral glucose metabolism in a mouse model of
      phenylketonuria.
AB  - Impairment of cognitive function is characteristic of untreated phenylketonuria
      in humans and in the pah(enu2) mouse model of phenylketonuria. We measured
      regional cerebral metabolic rate for glucose in the adult male pah(enu2) mouse to
      determine the effect of PKU on functional activity in brain and to discern what,
      if any, brain areas are affected. Our results demonstrate selective decreases (17
      21%) in regions thought to be involved in executive function. Regions most
      significantly affected include prelimbic, anterior cingulate, orbital frontal and
      perirhinal cortex. Sensory and motor areas of cortex and hippocampus were
      remarkably unaffected.

PMID- 17457694
TI  - Transferrin hypoglycosylation in hereditary fructose intolerance: using the clues
      and avoiding the pitfalls.
AB  - Hereditary fructose intolerance (HFI) is caused by a deficiency of aldolase B due
      to mutations of the ALDOB gene. The disease poses diagnostic problems because of
      unspecific clinical manifestations. We report three cases of HFI all of whom had
      a chronic disease with neurological, nephrological or gastroenterological
      symptoms, whereas nutritional fructose intolerance, the pathognomonic sign of
      HFI, was apparent only in retrospect. In all patients a hypoglycosylated pattern
      of transferrin isoforms was found but was misinterpreted as a sign of CDG Ix. The
      correct diagnosis was achieved with marked delay (26, 36 and 24 months,
      respectively) by sequencing of the ALDOB gene two common mutations were
      identified on both alleles or on one (A150P/A175D, A150P/-, and A150P/A175D). The
      diagnosis was further supported by normalization of transferrin isoforms on a
      fructose-free diet. Data available in two patients showed that following the
      fructose restriction the type I pattern of carbohydrate-deficient transferrin
      detectable on fructose-containing diet disappeared after 3-4 weeks. These cases
      illustrate that in the first years of life HFI may show misleading variability in
      clinical presentation and that protein glycosylation analysis such as transferrin
      isofocusing may give important diagnostic clues. However, care should be taken
      not to misinterpret the abnormal results as CDG Ix as well as to remember that a
      normal profile does not exclude HFI due to the possibility of spontaneous
      fructose restriction in the diet. The presented data also emphasize the
      usefulness of ALDOB mutation screening for diagnosis of HFI.

PMID- 17457695
TI  - Effects of a fat load and exercise on asymptomatic VLCAD deficiency.
AB  - The patient was identified via family screening at the age of 3 years when very
      long-chain acyl-CoA dehydrogenase (VLCAD) deficiency was diagnosed in his sister
      by newborn screening. Enzyme and molecular analyses confirmed VLCAD-deficiency
      (VLCADD). Until the age of 8 years no severe illnesses occurred and the patient
      was completely asymptomatic without a fat-reduced and fat-modified diet. On
      regular follow-up, creatine kinase (CK) and liver transaminases were always in
      the normal range. A long-chain fat load with 1.5 g/kg body weight did not result
      in clinical symptoms, nor in elevation of CK or liver transaminases. At the age
      of 8 years, the patient for the first time complained of recurrent muscle pain
      after exercise. CK concentrations were elevated up to 20,000 U/L during one of
      these episodes. Medium-chain fat was supplemented. With a medium-chain fat-rich
      meal directly before exercise, muscle pain after exercise clearly decreased. In
      asymptomatic mild VLCADD, a fat-reduced diet may not be necessary, whereas in
      later infancy and adolescence, strenuous physical exercise may require additional
      energy from medium-chain fat.

PMID- 17457693
TI  - Therapeutic concepts in succinate semialdehyde dehydrogenase (SSADH; ALDH5a1)
      deficiency (gamma-hydroxybutyric aciduria). Hypotheses evolved from 25 years of
      patient evaluation, studies in Aldh5a1-/- mice and characterization of gamma
      hydroxybutyric acid pharmacology.
AB  - We overview the pathophysiological bases, clinical approaches and potential
      therapeutic options for succinate semialdehyde dehydrogenase (SSADH; EC1.2.1.24)
      deficiency (gamma-hydroxybutyric aciduria, OMIM 271980, 610045) in relation to
      studies on SSADH gene-deleted mice, outcome data developed from 25 years of
      patient evaluation, and characterization of gamma-hydroxybutyric acid (GHB)
      pharmacology in different species. The clinical picture of this disorder
      encompasses a wide spectrum of neurological and psychiatric dysfunction, such as
      psychomotor retardation, delayed speech development, epileptic seizures and
      behavioural disturbances, emphasizing the multifactorial pathophysiology of SSADH
      deficiency. The murine SSADH-/- (e.g. Aldh5a1-/-) mouse model suffers from
      epileptic seizures and succumbs to early lethality. Aldh5a1-/- mice accumulate
      GHB and gamma-aminobutyric acid (GABA) in the central nervous system, exhibit
      alterations of amino acids such as glutamine (Gln), alanine (Ala) and arginine
      (Arg), and manifest disturbances in other systems including dopamine,
      neurosteroids and antioxidant status. Therapeutic concepts in patients with SSADH
      deficiency and preclinical therapeutic experiments are discussed in light of data
      collected from research in Aldh5a1-/- mice and animal studies of GHB
      pharmacology; these studies are the foundation for novel working approaches,
      including pharmacological and dietary trials, which are presented for future
      evaluation in this disease.

PMID- 17457696
TI  - Intermediate hyperhomocysteinaemia and compound heterozygosity for the common
      variant c.677C>T and a MTHFR gene mutation.
AB  - Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the regulation of
      plasma homocysteine levels. MTHFR deficiency, an autosomal recessive disorder,
      results in homocystinuria and hypomethioninaemia and presents with highly
      variable symptoms affecting many organs but predominantly the central nervous
      system. The common polymorphism of the MTHFR gene, c.677C>T, a known risk factor
      for elevated plasma homocysteine levels, occurs frequently in the caucasian
      population. In this study we investigated three subjects with moderate
      hyperhomocysteinaemia (total plasma homocysteine 72 micromol/L in case 1 and 90
      micromol/L in case 3, total non-protein-bound homocysteine 144-186 micromol/L in
      case 2) but different clinical presentation with no symptoms in case 1, muscle
      weakness at 17 years of age in case 2, and syncopes and cerebral convulsions at
      18 years of age in case 3. Each subject was compound heterozygous for the
      c.677C>T polymorphism and a novel mutation of the MTHFR gene (case 1: c.883G>A
      [p.D291N]; case 2: c.1552_c.1553delGA [p.E514fsX536]; case 3: c.616C>T
      [p.P202S]). Moderately decreased fibroblast MTHFR activity was associated with
      severely reduced affinity for NADPH and increased sensitivity to inhibition by S
      adenosylmethionine (AdoMet) in case 2, and with mild FAD responsiveness in case
      3. In case 1, fibroblast MTHFR activity was normal but the sensitivity to
      inhibition by AdoMet was slightly reduced. This study indicates that the sequence
      alteration c.677C>T combined with severe MTHFR mutations in compound heterozygous
      state may lead to moderate biochemical and clinical abnormalities exceeding those
      attributed to the c.677TT genotype and might require in addition to folate
      substitution further therapy to normalize homocysteine levels.

PMID- 17457698
TI  - COPD--moving beyond bronchodilation.
AB  - The burden of chronic obstructive pulmonary disease (COPD) remains very high.
      Till recently clinical approach of COPD patients was focused on measuring airflow
      limitation during exercise and treating airway obstruction with inhaled
      bronchodilators and corticosteroids. This approach stems from an old definition
      of COPD, mainly consisting of airflow limitation with poor reversibility after
      bronchodilation. The concept of COPD has changed strikingly in the last years.
      Many recent studies have shown that COPD is a systemic disease affecting not only
      the lungs but many other organs of the patient. Laboratory cardiopulmonary
      exercise testing assesses physiological and biological reserves. However, it is
      not the most suitable test to assess the functional state of a systemic disease
      such as COPD. We need simpler exercise tests that can be used on larger scales.
      The 6-minute walk test has been shown to be highly reproducible and reflects real
      life limitations of these patients better. It allows precise measurements of
      medical intervention and is a good predictor of mortality, provided clinicians
      respect the defined standards of this test. It should be associated with a more
      systemic index such as the BODE index to better find disease-modifying
      interventions and improve the outcome of COPD patients. On the other hand routine
      measurement of spirometry in the general population by primary care physicians
      should be promoted as it decreases smoking habits and helps better detecting and
      management of COPD patients. Specialists should support primary care physicians
      to spread these new concepts of COPD throughout the medical community.

PMID- 17457697
TI  - Fatigue in breast cancer survivors two to five years post diagnosis: a HEAL Study
      report.
AB  - PURPOSE: The purpose of this study was to estimate prevalence of fatigue,
      identify correlates of fatigue and evaluate the relationship between fatigue and
      health-related quality of life (HRQOL) in a large cohort of disease-free breast
      cancer survivors. METHODS: Participants are enrolled in the HEAL Study, a multi
      center prospective study of women diagnosed with in-situ to Stage IIIA breast
      cancer. HEAL participants (n = 1183) completed a baseline and a 24-month follow
      up interview. Women in this report (n = 800) also completed a quality of life
      questionnaire that included the Piper Fatigue Scale and the RAND SF-36 two to
      five years after diagnosis. Multivariate regression methods were used to identify
      significant factors associated with fatigue. SF-36 scores for fatigued survivors
      were compared to non-fatigued survivor scores and population norms. RESULTS:
      Forty-one percent of the breast cancer survivors were fatigued. Significant
      correlates of fatigue included pain, cognitive problems, physical inactivity,
      weight gain/personal appearance and antidepressant use. Fatigue was associated
      with poorer HRQOL, most notably in areas of role and social functioning.
      CONCLUSION: This study provides further support for the conclusion that a
      significant proportion of breast cancer survivors experience fatigue that
      compromises HRQOL two to five years post-diagnosis.

PMID- 17457699
TI  - Semen parameters in a fertile Swiss population.
AB  - BACKGROUND: The aim of this prospective study was to analyse the different sperm
      parameters of fertile Swiss men. To date there are no data regarding the quality
      of spermatozoa of fertile Swiss men. METHODS: We measured the ejaculates (pH,
      volume, concentration, motility, viability, morphology) of 34 men using strict
      inclusion criteria. The partners of these men had to be pregnant at the time of
      inclusion in the study and these pregnancies had to have been conceived
      spontaneously within 15 months. A questionnaire elucidated the consumption of
      alcohol, nicotine and drugs. Semen analysis was performed according to WHO
      criteria, with the exception of morphology, which was analysed according to
      Tygerberg's strict criteria. RESULTS: The mean age of the males studied was 34
      years. The semen analysis revealed the following following mean values: pH: 8,
      volume: 2.6 ml, concentration: 60 x 10(6)/ml, total count: 160 x 10(6),
      progressive motility: 42%, rapid progressive motility: 36%, viability: 47% and
      morphology: 8% normal forms. The consumption of alcohol, nicotine and drugs was
      low to moderate. CONCLUSIONS: No men fulfilled all criteria of normality in the
      different sperm parameters examined. The most striking results are that the upper
      limits of normal morphology and viability seem to be too high. Concentration and
      rapid progressive motility appear to have a high impact on fertility. The
      combination of several criteria is probably more predictive than a single
      parameter.

PMID- 17457700
TI  - Adherence to recommended standards of diabetes care by Swiss primary care
      physicians.
AB  - OBJECTIVES: To assess adherence to recommended standards of diabetes care by
      Swiss primary care physicians. METHODS: Medical files of community-based primary
      care physician were reviewed to assess adherence to recommended standards of
      diabetes care. These standards of care were based on a uniform set of definitions
      addressing medical care processes involved in the detection and follow-up of pre
      diabetic and diabetic patients. RESULTS: 186 physicians agreed to participate and
      3,682 medical files were assessed. The prevalence of diabetes was 11% and 5% had
      impaired glucose tolerance (pre-diabetic). Screening of diabetes based on family
      or personal history was reported for 83% of the patients and on cardiovascular
      risk factors for 69%. Counselling for dietary changes was reported for 91% of
      diabetic patients and for 79% for physical activity, but only for 66% and
      respectively 60% of pre-diabetic patients. Among diabetic patients, regular HbA1c
      control was reported for 65%, yearly fundoscopy for 62%, yearly feet examination
      for 65%, yearly microalbuminuria control for 49%, regular blood pressure control
      for 96%, and yearly lipid profile for 89%. Regular screening of microangiopathic
      complications was reported for only 33% of diabetic patients. CONCLUSION:
      Adherence to recommended standards of diabetes care displayed important
      variations among this convenience sample of Swiss primary care patients.
      Screening and counselling of diabetic patients were frequent, whereas counselling
      for lifestyle changes of pre-diabetic patients and regular follow-up of
      microangiopathic complications among diabetic patients were suboptimal. These
      results could help to target areas of diabetes care that need to be addressed to
      improve adherence to recommended standards.

PMID- 17457701
TI  - Endoscopic access closure for direct implantation of valved stents.
AB  - OBJECTIVES: The off-pump trans left ventricular approach provides an alternative
      option for insertion of stented aortic valves of any size for endovascular
      replacement. One of the key steps in this procedure is the repair of the
      ventricle after catheter withdrawal. This study evaluates the reliability of a
      new device for sutureless and quick repair of the left ventricle access. METHODS:
      The Amplatz-nitinol occluder consists of two square heads that squeeze the
      ventricle wall between them thus sealing the ventricular defect. In four adult
      pigs weighing 55 kg, left thoracoscopy was performed to open the pericardium and
      visualise the cardiac apex. Following a heparin injection (100 U/kg) under ICUS
      and fluoroscopic control, we inserted a 30 F sheath into the epigastric area
      through the cardiac apex up into the left ventricle thus simulating the approach
      for an off-pump aortic valve replacement. The sheath was then removed and the
      ventricle closed with the occluder. Animals were followed-up for three hours; the
      haemodynamics and pericardial bleeding were recorded. The animals were then
      sacrificed and the gross anatomy of the heart was examined. RESULTS: The device
      was successfully deployed in four animals in less than one minute. ACT was above
      200 seconds in all cases. All animals survived the procedure with a mean arterial
      pressure of 50 +/- 15 mm Hg. Bleeding during deployment was 80 +/- 20 ml and over
      a 3 hour period was 800 +/- 20 ml. Examination of the gross anatomy examination
      demonstrated the correct positioning of the device. CONCLUSIONS: The occluder is
      easy to use and the procedure is feasible and reproducible. However, the occluder
      design requires technical improvements in order to reduce bleeding before it can
      be used clinically.

PMID- 17457702
TI  - [Rare primary headache syndromes].
AB  - Primary headaches include common forms such as migraine, tension-type headache,
      and the less frequent cluster headache. Besides, several uncommon primary
      headaches were included in the section on 'Cluster headache and other trigeminal
      autonomic neuralgias' (section 3) and 'Other primary headaches' (section 4) in
      the second edition of the International Classification of Headache Disorders
      (ICHD-II, 2004). Since the prevalences of these uncommon headaches are quite low,
      datas related to clinical features, physiopathology and management are still
      controversial. While paroxysmal hemicrania, short-lasting unilateral neuralgiform
      headache attacks with conjunctival injection and tearing (SUNCT) are listed in
      the third section, hemicrania continua (HC) with not prominent autonomical signs
      are classified in the fourth section in the ICHD-II classification. The fourth
      section also includes other rare primary headache syndromes. In this review, some
      of the uncommon primary types of headache will be discussed. Even though these
      headaches are reported seldomly, the prevalences are possibly higher than known.
      It is of importance to recognize these uncommon disorders, since their management
      differs from common primary headaches.

PMID- 17457703
TI  - [Is childhood migraine an immature form of adult migraine?].
AB  - Childhood migraine is a common problem among the primary complaints of the
      pediatric population. But for the general practitioners there are little known
      about clinical characteristics and management strategies. Headache practitioners
      commonly notice the age related differences of headache characteristics and
      management schedules. This paper primarily aimed to answer the question if
      pediatric migraine is an unmaturated form of adult migraine, by discussing the
      pathophysiological basis, clinical forms and management strategies.

PMID- 17457704
TI  - [Osteoarthritis and pain].
AB  - Osteoarthritis (OA) is one of the most common health problems in the aging world.
      Pain and stiffness are the most prominent symptoms. Despite there are numerous
      risk factors that to be considered as responsible, the exact pathophysiology
      remains uncertain. According to this enigma, there isn't any single mechanism
      that explains emerge of pain in OA. Pain experienced in osteoarthritic joint may
      not always be caused by local pathology; there are also neurologic, neuromuscular
      and psychosocial influences. Understanding more about the pain mechanism might
      help us to develop better treatment options.

PMID- 17457705
TI  - [Effect of ondansetron in lower extremity bone surgery on morphine and tramadol
      consumption using patient controlled analgesia].
AB  - In this study, we aimed to assess the effect of administration of ondansetron on
      morphine and tramadol consumptions. After approval by the ethics committee, 120
      patients with ASA status I or II, who will undergo elective lower extremity
      surgery, were included in the study. Patients were randomly divided into 4 groups
      following the anesthesia induction. Group I received tramadol as PCA with an
      infusion of 0.3 mg/kg following a loading dose of 1.5 mg/kg administered 1 hour
      before the end of the surgery. Group II received ondansetron 0.1 mg/kg following
      induction of anesthesia, additionally. Group III received morphine as PCA with an
      infusion following a loading dose of 0.15 mg/kg administered 30 minutes before
      the end of surgery. Group IV received ondansetron 0.1 mg/kg following induction
      of anesthesia, additionally. Pain scores(VAS), nausea, vomitting and sedation
      scores, analgesic consumptions and adverse effects were recorded at 5th, 15th,
      30th, 45th minutes and 4th, 8th, 12th and 24th hours postoperatively.
      Postoperative VAS, nausea, vomitting and sedation scores were similar among the
      groups. The analgesic consumption was found significantly higher at 4th, 8th,
      12th and 24th hours in group II. No statistically significant difference was
      found in analgesic consumption between group III and IV at all times. We
      concluded that, ondansetron, when administered as nausea prophylaxis in patients
      receiving tramadol and morphine as PCA, did not effect morphine consumption
      whereas did increased tramadol consumption.

PMID- 17457706
TI  - Preemptive intraarticular tramadol for pain control after arthroscopic knee
      surgery.
AB  - The purpose of this study was to determine the effectiveness of intraarticular
      (ia) bupivacaine and tramadol injection and preemptive intraarticular tramadol in
      providing pain control after arthroscopic knee surgery. Following local research
      ethics committee approval, 60 patients were assigned in a randomized manner into
      three groups: Group I received ia 20 ml of 0.25 % bupivacaine at the end of the
      operation, Group II received ia 20 ml of 0.25 % bupivacaine and 100 mg of
      tramadol at the end of the operation and Group III received ia 100 mg of tramadol
      diluted in 20 ml of saline solution 30 minutes before skin inscision and 20 ml of
      0.25% bupivacaine at the end of the operation as well. Analgesic duration, total
      analgesic consumption and postoperative VAS pain scores recorded at rest and with
      movement were significantly lower and patient satisfaction was significantly
      higher in Group II and III, compared to Group I. Total analgesic consumption and
      the number of patients requiring supplementary analgesics were significantly
      lower in the preemptive tramadol group compared to the postoperative tramadol
      group. In conclusion, preemptive ia tramadol provided effective and reliable pain
      control after artroscopic knee surgeries and may be preferred to postoperative
      administration.

PMID- 17457707
TI  - [Comparison of phantom limb pain or phantom extremity sensation of upper and
      lower extremity amputations].
AB  - The aim of this retrospective study is to evaluate the upper and the lower
      extremity amputations with regard to phantom pain, phantom sensation and stump
      pain. A questionnaire consisting of 23 questions was send to the patients who
      underwent upper or lower extremity amputation surgery between 1996- 2005. The
      patients were questioned for the presence of phantom pain and sensations and if
      they existed for the frequency, intensity, cause of amputation, pre-amputation
      pain, stump pain, usage of artificial limb. Totally 147 patients were included
      and the response rate was 70 %. The incidence of phantom pain in Upper Extremity
      Group was 60 % and 65.8% in Lower Extremity Group. The incidence of phantom
      sensations was 70.7% in Upper Extremity Group and 75.6% in Lower Extremity Group.
      There was no significant difference between two groups considering in phantom
      pain and phantom sensations. The phantom pain was significantly higher in
      patients who lost dominant hand, experienced pre amputation pain and suffered
      stump pain. There were no significant differences in regard to phantom pain and
      sensation between upper and lower extremity amputations. However the presence of
      preamputation pain, stump pain and amputation of dominant hand were found as risk
      factors for the development of phantom pain.

PMID- 17457708
TI  - [Pain and pain behavior].
AB  - Pain is an unpleasant sensory and emotional experience associated with actual or
      potential tissue damage. Behavioral manifestation of pain, distress, and
      suffering have been characterized as pain behaviors. Pain behavior is the way
      individuals think, feel, and act in relation to their pain status. Pain behaviors
      are either adaptive or pathological, as when the pain behavior is
      disproportionate to the objective pathology. It's reported that when pain
      behavior exists in patients with pain, a psychiatric disorder might to increase
      pain. The relation between psychological factors and pain behavior is
      investigated in several studies.

PMID- 17457709
TI  - [Adjuvant analgesics in pain management].
AB  - The term adjuvant analgesics describes any drug with a primary indication other
      than pain, but with analgesic properties in some painful conditions. Adjuvant
      analgesics often are administered as first-line drugs in the treatment of chronic
      non-malignant pain. The group includes numerous drugs in diverse classes. Some
      adjuvant analgesics possess analgesic properties in several types of pain,
      whereas others are specific for neuropathic pain, or nociceptive pain.
      Antidepressants, anticonvulsants, neuroleptics, antiarrythmics, antihistaminics,
      NMDA receptor-antagonists, steroids, muscle relaxants, bisphosphonates, and
      radiopharmaceuticals are adjuvant agents. This article reviews the evidence
      supporting the use of adjuvant analgesics for the treatment of pain and
      emphasizes medical dosages, side effects, and drug interactions.

PMID- 17457710
TI  - [Migraine and cortical spreading depression].
AB  - Migraine is an episodic headache disorder accompanied by various neurological,
      gastrointestinal and autonomic changes. In one fifth of the migraineurs, a
      neurological disturbance (visual, sensory or motor) appears during or before the
      development of the headache called migraine aura. Cortical spreading depression
      (CSD) is a transient neuronal depolarization that spreads across unilateral
      hemisphere from a focus and is followed by a long-lasting depression of neuronal
      activity. CSD was proposed to be the underlying phenomenon of the migraine aura
      as it propagates at a similar velocity with visual scotomata and the transient
      cortical oligemia seen in migraineurs during the aura phase. This data, enabling
      a better understanding of migraine pathophysiology, will result in new insights
      into the treatment of other neurological disorders such as cerebrovascular
      disorders, transient global amnesia, traumatic brain injury, in whose
      pathophysiology CSD is supposed to take part, beside the treatment of migraine
      itself.

PMID- 17457711
TI  - [Transdermal fentanyl for neuropathic pain: a case report].
AB  - The mechanisms responsible for neuropathic pain are not fully understood. Most
      treatment modalities are ineffective or insufficient for this important clinical
      condition. Better understanding of pain mechanisms and opioid drug action has
      widened the indications for opioids in pain therapy of non-malignant pain
      including neuropathic pain. In this report of a female patient with chronic non
      malignant neuropathic pain was followed-up for pain and side effects, for
      approximately fourteen months with the use of transdermal fentanyl (TDF). Pain
      reduction was good throughout the study. Severe side effects did not occur. TDF
      was effective and well tolerated in the treatment of chronic neuropathic pain of
      non-malignant origin.

PMID- 17457712
TI  - [Investigation of nurses' pain related knowledge, attitude and clinical decision
      making skills].
AB  - The purpose of this study was to investigate the nurses' ain related knowledge,
      attitude and clinical decision making skills. Three instruments were used in the
      study: (1) Nurses' Introduction Form, (2) The Nurses' Knowledge and Attitudes
      Questionnaire and (3) Clinical Decision Making Survey Questionnaire developed by
      McCaffery and Ferrell was translated into Turkish and used with permission. The
      results showed that many nurses have inadequate knowledge about pain assessment
      and management, nurses' (% 47.4) did not observe patient's behaviors to
      determine/assess the patient's intensity of pain and % 74.5 of nurses' did not
      use pain assessment scales to measure the patient's pain.

PMID- 17457713
TI  - The effect of 3-in-1 femoral nerve block with ropivacaine 0.375% on postoperative
      morphine consumption in elderly patients after total knee replacement surgery.
AB  - Total knee replacement (TKR) is one of the most painful orthopedic surgical
      procedures. This study was aimed to investigate the effect of a single-shot
      preoperative 3-in-1 femoral nerve block on postoperative pain by using 0.375%
      ropivacaine, and on the consumption of morphine by using PCA following the TKR
      surgery. Side effects were also evaluated in this setting. 34 patients were
      included in this study. Group R (n=17) received a 3-in-1 femoral nerve block
      (FNB) with 40 mll of ropivacaine 0.375%. Group S (n=17) received only a 2 mg
      loading dose of morphine 30 minutes before the end of surgery, and no block was
      performed. Both groups received general anesthesia and postoperatively had a PCA
      pump programmed to deliver morphine. VAS scores at rest, morphine consumption and
      adverse effects were recorded. Two patients were excluded from each group. Pain
      scores at 0, 1, 2, 3, 4, 6, 8 postoperative hours were significantly lower in
      group R in resting position (p<0.05). Group R experienced no pain at the recovery
      room and this state lasted 8 hours after the surgery while group S reached the
      acceptable score (VAS ? 3) one hour after leaving the recovery room. The morphine
      requirement was significantly lower in Group R at 12, 18, 24, 48 hr after TKR
      (p<0.001). Side effects were also lower in this group. Preoperative single-shot 3
      in-1 FNB with 40 cc of ropivacaine 0.375% provides better VAS scores, less
      morphine consumption and fewer side effects in elderly patients when compared to
      the group with no block.

PMID- 17457714
TI  - [The prevalence of low back pain and its relationship with household jobs and
      other factors in a group of women in a rural area in Manisa].
AB  - The aims of this cross-sectional study were to determine the prevalence of low
      back pain and to evaluate the effects of household jobs on low back pain in women
      living in a rural setting in Manisa. Study population is consisted of 302 women
      and cluster sampling is performed according to percentage of health center
      district populations. Participation ratio of this study was 89.1%. Univariete and
      multivariete risk approach in 95% confidence interval and t test were performed
      in data analysis. Brief Disability Questionnaire was applied to the study group.
      Life time and point prevalence of low back pain were determined 79.2% and 34.9%
      of the study group. Low back pain risk in 95 % CI was higher in wrong posture
      during ironing, heavy load lifting, overweight/obesity and disability 2.2 (1.1-
      4.5), 4.5 (2.1-9.2), 3.8 (1.7-8.3) and 9.2 (4.3-19.7) times respectively. For
      preventive health measures it is necessary to apply ergonomic working conditions
      and to give appropriate postural habits to women.

PMID- 17457715
TI  - Efflux pumps as antimicrobial resistance mechanisms.
AB  - Antibiotic resistance continues to hamper antimicrobial chemotherapy of
      infectious disease, and while biocide resistance outside of the laboratory is as
      yet unrealized, in vitro and in vivo episodes of reduced biocide susceptibility
      are not uncommon. Efflux mechanisms, both drug-specific and multidrug, are
      important determinants of intrinsic and/or acquired resistance to these
      antimicrobials in important human pathogens. Multidrug efflux mechanisms are
      generally chromosome-encoded, with their expression typically resultant from
      mutations in regulatory genes, while drug-specific efflux mechanisms are encoded
      by mobile genetic elements whose acquisition is sufficient for resistance. While
      it has been suggested that drug-specific efflux systems originated from efflux
      determinants of self-protection in antibiotic-producing Actinomycetes,
      chromosomal multidrug efflux determinants, at least in Gram-negative bacteria,
      are appreciated as having an intended housekeeping function unrelated to drug
      export and resistance. Thus, it will be important to elucidate the intended
      natural function of these efflux mechanisms in order, for example, to anticipate
      environmental conditions or circumstances that might promote their expression
      and, so, compromise antimicrobial chemotherapy. Given the clinical significance
      of antimicrobial exporters, it is clear that efflux must be considered in
      formulating strategies for treatment of drug-resistant infections, both in the
      development of new agents, for example, less impacted by efflux or in targeting
      efflux directly with efflux inhibitors.

PMID- 17457716
TI  - Molecular pathogenesis of inflammatory bowel disease: genotypes, phenotypes and
      personalized medicine.
AB  - Crohn's disease (CD) and ulcerative colitis (UC), also known as inflammatory
      bowel diseases (IBD), are characterized by chronic inflammation of the
      gastrointestinal tract. IBD is among the few complex diseases for which several
      genomic regions and specific genes have been identified and confirmed in multiple
      replication studies. We will review the different loci implicated in disease risk
      in the context of three proposed mechanisms leading to chronic inflammation of
      the gut mucosa: 1) deregulation of the innate immune response to enteric
      microflora or pathogens; 2) increased permeability across the epithelial barrier;
      and 3) defective regulation of the adaptive immune system. As our knowledge of
      genetic variation, analytical approaches and technology improves, additional
      genetic risk factors are expected to be identified. With the identification of
      novel risk variants, additional pathophysiological mechanisms are likely to
      emerge. The resulting discoveries will further our molecular understanding of
      IBD, potentially leading to improved disease classification and rational drug
      design. Moreover, these approaches and tools can be applied in the context of
      variable drug response with the goal of providing more personalized clinical
      management of patients with IBD.

PMID- 17457717
TI  - The workings of the amyloid diseases.
AB  - The amyloidoses constitute a large group of diseases caused by an alteration in
      the conformation and metabolism of several globular proteins which, under
      particular conditions, deposit in tissues as insoluble fibrillar aggregates. To
      date, at least 24 different proteins have been recognized as causative agents of
      amyloid diseases. Despite a high heterogeneity in amino acid sequence, three
      dimensional structure, and biological function, all amyloidogenic proteins share
      a reduced folding stability, a strong propensity to acquire more than one
      conformation, and the capacity to form almost indistinguishable amyloid fibrils.
      In some cases, the generation of an aggregation-prone state can be triggered or
      enhanced by the occurrence of mutations, a proteolytic cleavage, or a seeding
      process. The interaction between the amyloidogenic precursor, some common
      components of amyloid deposits, and the extra-cellular environment also plays a
      role in fibrillogenesis and in particular in the organ tropism of amyloid
      deposition. The process of amyloid fibril formation exerts a cytotoxic effect,
      resulting in tissue damage and organ dysfunction. Prefibrillar aggregates are
      thought to have an active part in this process. Due to the pathogenic complexity
      of amyloid diseases, the integration of several therapeutic interventions
      involving different critical levels of the amyloidogenic cascade is envisaged.

PMID- 17457718
TI  - The broken genome: genetic and pharmacologic approaches to breaking DNA.
AB  - The RecQ family of DNA helicases consists of specialized DNA unwinding enzymes
      that promote genomic stability through their participation in a number of
      cellular processes, including DNA replication, recombination, DNA damage
      signaling, and DNA repair pathways. Mutations resulting in the inactivation of
      some but not all members of the RecQ helicase family can lead to human syndromes
      which are characterized by marked chromosomal instability and an increased
      predisposition to cancer. An evolutionarily conserved interaction between RecQ
      helicases and topoisomerase 3s has been established, and this interaction is
      important in the regulation of recombination and genomic stability.
      Topoisomerases are critical in the cell because they relieve helical stress that
      arises when DNA is unwound. Topoisomerases function by breaking and rejoining
      DNA. By inhibition of the rejoining function, topoisomerase inhibitors are potent
      chemotherapeutic agents that have been used successfully in the treatment of
      hematologic malignancies and other cancers. This review discusses the roles of
      RecQ helicases in genomic stability, the interplay between RecQ helicases and
      topoisomerase 3s, and current and future prospects for targeting these
      interactions to develop novel anticancer therapies.

PMID- 17457719
TI  - The LDL receptor-related protein (LRP) family: an old family of proteins with new
      physiological functions.
AB  - The low-density lipoprotein (LDL) receptor is the founding member of a family of
      seven structurally closely related transmembrane proteins (LRP1, LRP1b,
      megalin/LRP2, LDL receptor, very low-density lipoprotein receptor, MEGF7/LRP4,
      LRP8/apolipoprotein E receptor2). These proteins participate in a wide range of
      physiological processes, including the regulation of lipid metabolism, protection
      against atherosclerosis, neurodevelopment, and transport of nutrients and
      vitamins. While currently available data suggest that the role of the LDL
      receptor is limited to the regulation of cholesterol homeostasis by receptor
      mediated endocytosis of lipoprotein particles, there is growing experimental
      evidence that the other members of the gene family have additional physiological
      functions as signal transducers. In this review, we focus on the latest
      discovered functions of two major members of this family, LRP1 and megalin/LRP2,
      and on the newly elucidated physiological role of a third member of the family,
      MEGF7/LRP4, which can also function as a modulator of diverse signaling pathways
      during development.

PMID- 17457720
TI  - Three circadian clock genes Per2, Arntl, and Npas2 contribute to winter
      depression.
AB  - BACKGROUND: Multiple lines of evidence suggest that the circadian clock
      contributes to the pathogenesis of winter depression or seasonal affective
      disorder (SAD). We hypothesized that sequence variations in three genes,
      including Per2, Arntl, and Npas2, which form a functional unit at the core of the
      circadian clock, predispose to winter depression. METHODS: In silico analysis of
      the biological effects of allelic differences suggested the target single
      nucleotide polymorphisms (SNPs) to be analyzed in a sample of 189 patients and
      189 matched controls. The most relevant SNP in each gene was identified for the
      interaction analysis and included in the multivariate assessment of the combined
      effects of all three SNPs on the disease risk. RESULTS: SAD was associated with
      variations in each of the three genes in gene-wise logistic regression analysis.
      In combination analysis of variations of Per2, Arntl, and Npas2, we found
      additive effects and identified a genetic risk profile for the disorder. Carriers
      of the risk genotype combination had the odds ratio of 4.43 of developing SAD as
      compared with the remaining genotypes, and of 10.67 as compared with the most
      protective genotype combination. CONCLUSION: Variations in the three circadian
      clock genes Per2, Arntl, and Npas2 are associated with the disease, supporting
      the hypothesis that the circadian clock mechanisms contribute to winter
      depression.

PMID- 17457721
TI  - The politics and science behind GMO acceptance.
AB  - The question of nutritional quality has arisen in the International Community
      over the last few years along with other important issues such as population
      aging, multipopulation societies, and political conflicts. The nutritional issue
      is questioned both quantitatively and qualitatively. It is well known that the
      planet faces enormous problems with food that is available. Nowadays 20% of the
      population consumes approximately 80% of the produced energy and natural
      resources. During the last 15 years, a series of food scares and crises (BSE,
      dioxin, foot and mouth disease, bird flu) have seriously undermined public
      confidence in food producers and operators and their capacity to produce safe
      food. As a result, food safety has become a top priority of the European
      legislative authorities. Genetically Modified Organisms (GMOs) is the new food
      safety concern which despite the intense reactions from Non Governmental
      Organizations and consumer organizations have entered our lives with inadequate
      legislative measures to protect consumers from their consumption. The GMO issue
      will be the issue for discussion in the long run not only for the European
      Community but also for the international community as far as scientific,
      economical, political, ideological, ethical, and human issues are concerned.
      These issues are discussed in this paper along with a case of study of GM fish.

PMID- 17457722
TI  - Application of Failure Mode and Effect Analysis (FMEA), cause and effect
      analysis, and Pareto diagram in conjunction with HACCP to a corn curl
      manufacturing plant.
AB  - The Failure Mode and Effect Analysis (FMEA) model has been applied for the risk
      assessment of corn curl manufacturing. A tentative approach of FMEA application
      to the snacks industry was attempted in an effort to exclude the presence of GMOs
      in the final product. This is of crucial importance both from the ethics and the
      legislation (Regulations EC 1829/2003; EC 1830/2003; Directive EC 18/2001) point
      of view. The Preliminary Hazard Analysis and the Fault Tree Analysis were used to
      analyze and predict the occurring failure modes in a food chain system (corn
      curls processing plant), based on the functions, characteristics, and/or
      interactions of the ingredients or the processes, upon which the system depends.
      Critical Control points have been identified and implemented in the cause and
      effect diagram (also known as Ishikawa, tree diagram, and the fishbone diagram).
      Finally, Pareto diagrams were employed towards the optimization of GMOs detection
      potential of FMEA.

PMID- 17457723
TI  - Guar gum: a miracle therapy for hypercholesterolemia, hyperglycemia and obesity.
AB  - The number of hypercholesterolemic and hyperglycemic people is increasing rapidly
      in the world. The prevention against these health problems is related to a
      complex management of conventional and non-conventional risk factors. The
      inclusion of dietary fiber in the diet is the right approach to reduce these
      risks. Cholesterol and glucose lowering effects are most often associated with
      gelling, mucilaginous, and viscous fibers such as guar gum, an edible thickening
      agent. It has widespread applications in the food industry due to its ability to
      hydrate without heating. The demand for guar gum is still growing rapidly because
      in addition to its indispensable role in lowering serum cholesterol and glucose
      levels, it is also considered helpful in weight loss programs. The main thrust of
      therapeutic and medicinal properties lies in the soluble dietary fiber content of
      guar gum to improve the serum biochemical profile of human and non-human
      primates, reducing total serum cholesterol, triglycerides, increasing the high
      density lipoprotein cholesterol level, and the management of glycemic indices and
      obesity. Among the various intervention strategies, diet diversification is the
      right approach to overcome these problems. Composite flours containing wheat and
      legumes have proven practical uses and are being utilized in many parts of the
      world to improve the nutritional and functional properties of flour. The main
      focus of this manuscript is to review the available information on various
      aspects of guar gum with special reference to its effectiveness in reducing the
      cardiovascular disease risk, diabetes and weight loss programs.

PMID- 17457724
TI  - Food content, processing, absorption and metabolism of onion flavonoids.
AB  - The question as to how far the development of chronic diseases in humans depends
      on diet still remains open. Simultaneously, epidemiological studies suggest the
      consumption of a flavonoids rich diet might decrease the risk of degenerative
      changes and certain diseases. The intake of this group of compounds as to quality
      and quantity depends on dietary habits and a widespread presence of quercetin in
      the diet makes this compound one of the key factors. Onion, one of the richest
      and most common quercetin sources, was particularly often studied in different
      aspects. Quercetin is present in onion mainly as glycosides, of which the
      distribution within the onion bulb changes in onion processing, and biological
      activities attracted a lot of attention. Especially antioxidative activity
      demonstrated in vitro was initially associated with most of the beneficial
      effects of quercetin on the human body. However, after ingestion quercetin
      undergoes extensive metabolism and microbial action resulting in its altered or
      degraded structure; therefore, most of the effects shown in in vitro experiments
      with the pure compound cannot be directly extrapolated to in vivo systems. Yet,
      this does not mean that quercetin simultaneously loses its positive impact on
      consumer health. Even after being metabolized it may still affect the redox
      balance by inducing antioxidative and detoxifying enzymes or compounds which may
      be involved in sustaining homeostasis.

PMID- 17457725
TI  - Natural biopolymer-based nanocomposite films for packaging applications.
AB  - Concerns on environmental waste problems caused by non-biodegradable
      petrochemical-based plastic packaging materials as well as the consumer's demand
      for high quality food products has caused an increasing interest in developing
      biodegradable packaging materials using annually renewable natural biopolymers
      such as polysaccharides and proteins. Inherent shortcomings of natural polymer
      based packaging materials such as low mechanical properties and low water
      resistance can be recovered by applying a nanocomposite technology. Polymer
      nanocomposites, especially natural biopolymer-layered silicate nanocomposites,
      exhibit markedly improved packaging properties due to their nanometer size
      dispersion. These improvements include increased modulus and strength, decreased
      gas permeability, and increased water resistance. Additionally, biologically
      active ingredients can be added to impart the desired functional properties to
      the resulting packaging materials. Consequently, natural biopolymer-based
      nanocomposite packaging materials with bio-functional properties have a huge
      potential for application in the active food packaging industry. In this review,
      recent advances in the preparation of natural biopolymer-based films and their
      nanocomposites, and their potential use in packaging applications are addressed.

PMID- 17457727
TI  - Abortion and politics in Nicaragua: the women's movement in the debate on the
      Abortion Law Reform 1999-2002.
AB  - This paper analyses discussion on a proposed reform to the abortion law in
      Nicaragua between 1999 and 2002, as a struggle between different actors -
      politicians, religious leaders, doctors and feminists - over the meaning of
      abortion, motherhood and sexuality, and ultimately the value of women's lives. It
      shows how the interplay of gender discourses and political practices shaped the
      process of discussion: on one hand by making a broad alliance against abortion
      possible, on the other by highlighting the contradictory role of the women's
      movement in this discussion, between a dominant leadership and a low mobilizing
      capacity. The paper argues for the need of an inwards oriented process within the
      women's movement, that departs from the recognition of the personal issues at
      stake for women in order to break the silence surrounding abortion, such as
      prevailing feelings of fear and guilt. This entails recognition of the limits of
      the liberal feminist claim to 'abortion as a free choice', as a discourse of
      rights that is disconnected from the everyday life conditions and constraints
      under which women make choices and develop their notions of rights.

PMID- 17457728
TI  - 'It's really a hard life': love, gender and HIV risk among male-to-female
      transgender persons.
AB  - Scientific studies demonstrate high rates of HIV infection among male-to-female
      (MTF) transgender individuals and that stigma and discrimination place MTFs at
      increased risk for infection. However, there is little research examining how
      gender roles contribute to HIV risk. This paper reports on in-depth interviews
      with 20 MTFs attending a community clinic. Data reveal that stigma and
      discrimination create a heightened need for MTFs to feel safe and loved by a male
      companion and that in turn places them at a higher risk for acquiring HIV. Male
      to-female transgender individuals appear to turn to men to feel loved and
      affirmed as women; their main HIV risk stems from their willingness to engage
      with sexual partners who provide a sense of love and acceptance but who also may
      also request unsafe sexual behaviours. A model illustrating how HIV risk is
      generated from stigma and discrimination is presented.

PMID- 17457729
TI  - 'Marriage is sacred': the religious right's arguments against 'gay marriage' in
      Australia.
AB  - In 2004, the Australian government legislated to prohibit 'gay marriage'; the
      religious right had lobbied vigorously for passage of this legislation. Drawing
      on Durkheim's theory of sacred and profane, this paper examines the argument
      proffered by right-wing Christians that allowing legalised unions between
      lesbians and between gay men would seriously undermine the institution of
      marriage and the family. Claims about the spectre of gays and lesbians marrying
      reveal a deeper unease about the status of heterosexual marriage and the nuclear
      family. These concerns, in turn, house a deeper unease about the nature and place
      of masculinity in contemporary Australian society. This disquiet about
      masculinity and masculine authority is isomorphic with concerns about challenges
      to the notion of an objective epistemological order. Marriage and nature are both
      sacred in Durkheimian terms because they must be radically separated from matters
      profane. By locating heterosexual marriage within the domain of nature, it is
      protected from contact with things that threaten its sacred status. However,
      Durkheim's theory of the sacred is simultaneously an account of the exercise of
      ideological power. Attempts to cast heterosexual marriage as sacred and,
      therefore, as inviolate are inextricably linked with attempts to protect an
      epistemological order linked to masculine authority.

PMID- 17457730
TI  - Sexual objectification and the construction of whiteness in the gay male
      community.
AB  - This paper presents interview data and media analysis on the gay male community
      in the USA. It describes how sexual objectification is more than the outcome of
      racism in the gay male community. Sexual objectification of gay men of colour in
      the USA produces a white sexual community. Ideologies of inclusivity and non
      discrimination blind white gay men to the harmful effects of sexual
      objectification. Moreover, discussing negative effects of objectification is met
      with considerable resistance. The experiences of African American men, described
      in this paper, show the pervasiveness of sexual objectification. The sexual
      objectification of men of colour forces them to play specific roles in sexual
      encounters that are not necessarily of their own choosing.

PMID- 17457731
TI  - Don't bother to wrap it: online Giftgiver and Bugchaser newsgroups, the social
      impact of gift exchanges and the 'carnivalesque'.
AB  - At online internet newsgroups, members who self-identify as Giftgivers and
      Bugchasers post messages describing exchanging HIV as a gift, as the Gift. Using
      the literature on the social function of gift exchanges, this paper considers how
      Giftgiver and Bugchaser messages mobilize the language of gifts. In doing so,
      newsgroup members generate an ontological narrative wherein HIV, as the Gift,
      promotes social bonds, the creation and maintenance of self identity and social
      roles, and the meeting of particular goals. Thus the Gift appears to fulfill (at
      least discursively) many of the social functions of gift exchanges as described
      in the literature. Online newsgroups function as fora for the expression of a
      contrarian, transgressive HIV/AIDS narrative and act as 'carnivalesque' spaces in
      which normative social roles and meaning are inverted in the establishment of a
      realm whereby HIV becomes a gift.

PMID- 17457732
TI  - Regulation of sexuality in Indonesian discourse: normative gender, criminal law
      and shifting strategies of control.
AB  - This paper examines changes in the regulation of sexuality in Indonesia in the
      period since 1980 as seen through state, religious and lesbian and gay activist
      discourses on sexuality. Three different eras during that period of Indonesian
      history are compared. Under the New Order regime of Suharto, the Indonesian state
      sought to control sexuality through a deployment of gender. During the 1990s,
      state Islamic discourses of sexuality shifted in response to international
      pressures to support same-sex marriage and sexual rights. During the third period
      following the end of the Suharto regime in 1998, a conservative Islamic minority
      pushed for more restrictive laws in the State Penal Code, initiating intense
      public debate on the role of the state in questions of sexuality and morality.
      Over this time period, the dominant discourse on sexuality moved from
      strategically linking normative gender with heterosexuality and marriage to
      direct attempts to legislate heterosexual marriage by criminalizing a wide range
      of sexual practices.

PMID- 17457733
TI  - Childhood sexuality and rights in the context of HIV/AIDS.
AB  - The primary objective in this study was to explore what HIV and AIDS mean to
      seven- and eight-year-old children in South Africa and how sexual and gender
      dynamics are embedded within these meanings. Against representations that
      associate young children with innocence, the paper argues for a more capacious
      view of young children as sexual and gendered agents with the ability to exercise
      their rights. In contrast to research that addresses children as relatively
      passive desexualised beings, focusing on their dependence on adults, their
      innocence and their need for protection, this paper examines how HIV and AIDS are
      constructed and negotiated by young people. It views children not simply in terms
      of their need for sexual rights but as potentially active participants in the
      negotiation of their rights. Viewing children's rights as highly contested, the
      notion that young children have sexual rights opens up possibilities for children
      (including those from marginalised groups) to talk about their concerns and
      pleasures, fears and hopes, as well as issues relating to sexual rights and
      resistances. By working creatively with teachers, it may be possible to broaden
      young children's knowledge of HIV and AIDS and sexuality within a more supportive
      environment.

PMID- 17457734
TI  - Adapting the Canadian Occupational Performance Measure for use in a paediatric
      clinical trial.
AB  - BACKGROUND: The Canadian Occupational Performance Measure (COPM) is a commonly
      used outcome measure in rehabilitation. In this study it was adapted for very
      young children by deleting paid/unpaid work and household management categories
      and having parents act as proxies to rate child performance and their own
      satisfaction. PURPOSE: To assess the internal consistency reliability, content
      and construct validity, responsiveness, and impact of half scores (20 not 10
      point scale) of the adapted COPM. METHOD: Parent proxies of subjects aged 2 - 8
      (mean 3.9) years with spastic hemiplegic cerebral palsy (n = 41) participating in
      a clinical trial. There was a total of 214 occupational performance problems for
      analysis and an additional 56 which had used half score ratings. Internal
      consistency reliability and construct validity were evaluated using Cronbach
      alpha statistic. Proxy views explored content validity. Responsiveness was
      evaluated using pre-post intervention scores and a comparison with Goal
      Attainment Scaling scores which were assumed to be a suitable benchmark measure.
      The effect of half scores was assessed by two-sample t-tests. RESULTS: The COPM
      adaptations did not have a negative impact on internal consistency reliability as
      this was acceptable for performance (0.73) and satisfaction (0.83). The high
      Cronbach alpha scores indicated good construct validity. Content of occupations
      and rating approach was considered valid by proxies. Use of half scores did not
      result in significantly different performance ratings, but mean satisfaction
      ratings were significantly higher when half scores were used (p = 0.0001). This
      suggests that half scores may provide more precise proxy satisfaction ratings,
      but at the cost of rigour as internal consistency with satisfaction half scores
      was lower (0.63 vs. 0.82). Responsiveness to change in clinical status was
      demonstrated by significant pre-post scores and moderate correlations with goal
      attainment scores. CONCLUSION: The adapted COPM is a psychometrically robust tool
      and the use of half scores is not recommended.

PMID- 17457735
TI  - The development of a clinical practice stroke guideline for physiotherapists in
      The Netherlands: a systematic review of available evidence.
AB  - PURPOSE: To develop a clinical practice guideline for the physiotherapy
      management of patients with stroke as support for the clinical decision-making
      process, especially with respect to the selection of appropriate interventions,
      prognostic factors and outcome measures. INTRODUCTION: Physiotherapists have a
      high caseload of patients with stroke, so there is a need to identify effective
      evidence-based physiotherapy procedures. The availability of a guideline that
      includes information about prognostic factors, interventions, and outcome
      measures would facilitate clinical decision-making. METHOD: A systematic
      computerized literature search was performed to identify evidence concerning the
      use of: (i) prognostic factors related to functional recovery; (ii) physiotherapy
      interventions in patients with stroke; and (iii) outcome measures to assess
      patients' progress in functional health. Experts, physiotherapists working in the
      field of stroke rehabilitation, and a multidisciplinary group of health
      professionals reviewed the clinical applicability and feasibility of the
      recommendations for clinical practice and their comments were used to compose the
      definitive guideline. RESULTS: Of 9482 relevant articles, 322 were selected.
      These were screened for methodological quality. Seventy-two recommendations for
      clinical practice were retrieved from these articles and included in the
      guideline: Six recommendations concerned the prediction of functional recovery of
      activities of daily living (ADL), including walking ability and hand/arm use; 65
      recommendations concerned the choice of physiotherapy interventions; and 1
      recommendation concerned the choice of outcome instrument to use. A core set of
      seven reliable, responsive, and valid outcome measures was established, to
      determine impairments and activity limitations in patients with stroke.
      CONCLUSIONS: The guideline provides physiotherapists with an evidence-based
      instrument to assist them in their clinical decision making regarding patients
      with stroke. As most of the recommendations included in the guideline came from
      studies of patients in the post acute and chronic phase of stroke, and in general
      involved patients with less severe and uncomplicated stroke, more needs to be
      learned about the more complex cases.

PMID- 17457736
TI  - Characteristics of the Frenchay Activities Index one year after a stroke: a
      population-based study.
AB  - PURPOSE: To further describe the properties of Frenchay Activities Index (FAI)
      with special emphasis on relationships with stroke severity and cognition.
      METHODS: Survivors from a population-based first-ever stroke cohort (n = 246)
      were assessed with FAI one year post-stroke. At the same time patients were asked
      about their status pre-stroke. Stroke severity was assessed at baseline with the
      NIH stroke scale (NIHSS). Cognition was assessed at one year with the Mini Mental
      State Examination (MMSE). RESULTS: Pre-stroke and post-stroke FAI averaged at
      40.1 and 32.4, respectively. There was a floor effect post-stroke, where 17% had
      the lowest possible score. The sum score was related to age, but not to gender.
      Individual items, however, were gender-related. NIHSS was clearly related to the
      difference FAI pre-stroke - post-stroke, but individual variations were large.
      Individual NIHSS items differed regarding their impact on post-stroke FAI. MMSE
      post-stroke also has a clear relationship with FAI, but there are large
      individual variations. CONCLUSIONS: This study establishes a population-based
      standard for FAI scores one year after a stroke. The effects of stroke severity
      and cognition have been demonstrated. FAI gives useful information that is not
      obtained from basic ADL scales, such as the Barthel Index.

PMID- 17457737
TI  - The relationship between work function and low back pain history in
      occupationally active individuals.
AB  - PURPOSE: To investigate the relationship between work function and low back pain
      (LBP) history. STUDY DESIGN: Cross-sectional study. BACKGROUND: In some
      countries, traditional medical examinations do not assess work performance in
      people who continue working despite a history of LBP, although such assessment
      may be required. METHODS: A total of 100 industrial metal workers were assigned
      to groups with and without LBP history. Logistic regression and t-tests examined
      the associations between physical work performance (represented by dynamic
      strength evaluation) and the group, and compared worker performance between the
      two groups. Similar tests examined potentially confounding effects on group
      assignment. RESULTS: Work performance was significantly associated with the group
      in dynamic strength sub-tests assessing weight lifting and carrying. The weights
      handled were lower in the group with LBP history (p < 0.05). Only the workers'
      country of origin affected group assignment; adjustment for this factor, as well
      as for age and education improved the associations between work performance and
      the group. CONCLUSIONS: Workers with a history of LBP display decreased physical
      performance at work, which should be subject to further research and treated as a
      health-related problem in accordance with the ICF model.

PMID- 17457738
TI  - Are vertical meridian effects due to audio-visual interference? A new
      confirmation with deaf subjects.
AB  - PURPOSE: Specific increases of reaction times (RTs) were found in normal
      subjects, when endogenous spatial cues and targets were separated by the vertical
      visual meridian (VM) or by the vertical auditory (AM) meridian, when targets were
      either visual or auditory. The aim of this study was to assess if this effect
      could be attributed to longer RTs needed to shift activation between the
      hemispheres, or rather to different spatial maps underlying visual and auditory
      attention. METHOD: We tested the VM effect in deaf subjects. If the shifting of
      activation from one hemisphere to the other causes the increase in RTs, then no
      differences between normal and sensory disabled people should take place, as the
      incoming perceptual information in the residual modality uses the same neural
      pathways while crossing the vertical meridian. Conversely, if the vertical
      meridian effects are related to the spatial representation systems underlying
      endogenous orienting mechanisms, then the lack of the auditory perceptual system
      in deaf people may have determined different organization processes in the brain
      circuits, strongly affecting the orienting mechanisms of spatial attention.
      RESULTS: Compared with a control group of hearing subjects, we found no evidence
      of the VM effect in deaf subjects. CONCLUSIONS: This finding, jointly with those
      of a previous experiment which showed no AM effect on blind subjects (Olivetti
      Belardinelli & Santangelo 2005) supports the idea of different spatial maps
      underlying visual and auditory attention, and suggests that their co-existence
      may induce interference effects in space processing, giving rise to the
      anisotropic representation of visual and auditory spaces, observed in normal
      subjects.

PMID- 17457739
TI  - Predictors of functional disability in rheumatoid arthritis: results from a 13
      year prospective study.
AB  - PURPOSE: To explore the role of distress and social support as modifiers of
      functional disability in rheumatoid arthritis (RA). We hypothesized that: (a)
      higher inflammatory activity, more joint tenderness and more pain lead to more
      disability, and (b) that more distress and less social support lead to more
      disability and accelerate the disablement process by moderating the effects of
      inflammatory activity, joint tenderness and pain. METHODS: The study is a Dutch
      extension of the European Research on Incapacitating Diseases and Social Support
      (EURIDISS) which started with 292 patients. After five waves of data collection
      129 still participated. Correlational and hierarchical regression analyses were
      performed. RESULTS: In short-term RA, 68% of the variance in disability could be
      explained primarily by mean disability over the prior years. Other important
      predictors were inflammatory activity and pain. In long-term RA, 56% of the
      variance in disability could be explained primarily by mean disability over the
      prior years. Other important predictors were joint tenderness and pain. No clear
      moderator effects of distress and social support were found in short-term or long
      term RA. CONCLUSIONS: The results confirm the main pathway from pathology to
      disability in short-term and long-term RA, but do not provide support for the
      influence of distress and social support on the disablement process.

PMID- 17457740
TI  - Trends in Australian rehabilitation: reviving its humanitarian core.
AB  - PURPOSE: This paper discusses how vocational rehabilitation (VR) in Australia has
      been captured by economic concerns, leading to its failure to deliver promised
      outcomes. Both public and private sector VR in Australia have undergone
      significant changes over the last two decades. The demise of non-profit and
      socially-based rehabilitation in favour of fixed funding models (e.g., managed
      care or case-base funding), coupled with the growing emphasis on cost containment
      has placed many VR providers in an unfamiliar environment dominated by
      bureaucratic, legal, economic and political imperatives. Although it was expected
      that VR would address rising injury costs, its inability to do so has jeopardized
      its existence. CONCLUSION: Ironically, it is economic imperatives that are now
      prompting the re-invention of old concepts that appear to offer the same cost
      containment possibilities rehabilitation offered in the 1990s. The most
      significant among these trends are self-management, coordinated care, community
      rehabilitation and welfare-to-work incentives. Perhaps the major challenge now,
      however, is to define a new dimension for rehabilitation and capture the essence
      of these trends to ensure that they contribute to a possible revival of a model
      of VR that focuses on the client's broad social context and responds to client
      centred goals.

PMID- 17457741
TI  - A research study into the requirements of disabled residents for rehabilitation
      services in Beijing.
AB  - PURPOSE: Rehabilitation services need strengthening further. This study explores
      a sample of the population in Beijing in order to establish the extent of medical
      impairments and disabilities. It describes the present utilization of
      rehabilitation by different economic groups of the population and also explores
      the attitudes of these same groups to the concepts inherent in rehabilitation.
      The conclusions are that a considerable information program is needed to help
      people with disabilities to access and utilize services appropriately. Finally,
      it concludes that the present Rehabilitation Services need to be professionally
      improved and expanded. BACKGROUND: In China, the spectrum of disease is changing,
      along with the development of society, and progress in science and technology.
      The requirements of people for medical rehabilitation following major accidents,
      and acute or chronic disease, leading to disability and handicap, increase year
      by year. This is especially so now, with the added geriatric problems of an aging
      population. At present, rehabilitation services and resources within this country
      are limited. It is difficult to meet the immediate or long-term needs of disabled
      persons. Recently, there have been many national publications describing the
      requirements and discussing those factors which influence Rehabilitation Service
      provision, but much of this discussion has been theoretically based, rather than
      facing practical issues. We can find no studies describing the nature and extent
      of disabling disorders in the Beijing population and, in particular, few formal
      studies relating the provision of rehabilitation services to that population in
      need of this essential management process. We have therefore carried out a survey
      based study to demonstrate the present rehabilitation service requirements for
      disabled residents in some typical Beijing urban districts. We have also looked
      at those factors which influence clients to accept the various services which are
      available to them at present. This will, we suggest, provide an epidemiological
      and demographic analysis with data on which to base future policies for
      government services to best meet these requirements. METHOD: A series of
      comprehensive questionnaires were designed, in order to investigate the
      demographic characters, health conditions, knowledge of rehabilitation services,
      and social status of the interviewees. Some 460 disabled residents from three
      districts in the city of Beijing were selected. They were randomized, with multi
      stage cluster sampling for in-house survey. RESULTS: Some 74.78% of interviewees
      expressed a need for rehabilitation, at different levels, but only 26.73%
      received any services. Factors influencing requests for community rehabilitation
      services for disabled residents in Beijing included income, nature of disability,
      awareness of rehabilitation services and the nature of services supplied. The
      expressed needs for rehabilitation services by disabled residents in communities
      in Beijing urban districts are real, and are largely unmet. Only a few of the
      disabled received any services. Factors influencing disabled residents' abilities
      to access rehabilitation service, included the nature and degree of disability,
      the economic status of the residents, the quality and nature of the
      rehabilitation programs and treatment available, and the knowledge by clients of
      the existence and availability of these services. CONCLUSION: More effective
      measures need to be taken to make the appropriate Rehabilitation Services more
      available to community residents with medical disabilities.

PMID- 17457742
TI  - Feedback quality and environmentally friendly use of domestic central heating
      systems.
AB  - The study examined the influence of system-embedded feedback on user behaviour
      during the environmentally friendly operation of a central heating system. A PC
      based simulation, called CHESS, was developed to model the critical features of a
      central heating system. After having received 30 min of training on the
      simulation task, 60 participants worked on a series of operational scenarios
      under different levels of system feedback. In addition to the collection of
      various performance measures (e.g. energy consumption, energy wastage), a range
      of user variables was collected (e.g. environmental concern). As hypothesized,
      the results showed that increased feedback resulted in improved environmentally
      friendly performance and, more importantly, the specific feedback indicator
      influenced the type of strategy used to improve human - machine system
      performance. A major implication is that system designers need to develop
      feedback indicators that are chiefly influenced by user behaviour and are largely
      immune to factors that are beyond the user's control (e.g. weather conditions).

PMID- 17457743
TI  - Self-reported musculoskeletal problems amongst professional truck drivers.
AB  - Occupational driving has often been associated with a high prevalence of back
      pain. The factors that contribute to cause the pain are diverse and might include
      prolonged sitting, poor postures, exposure to whole-body vibration and other non
      driving factors such as heavy lifting, poor diet or other psychosocial factors.
      In Europe, truck drivers are likely to be considered an 'at risk' group according
      to the Physical Agents (Vibration) Directive and therefore risks will need to be
      reduced. This questionnaire-based study set out to examine the relationship
      between musculoskeletal problems and possible risk factors for HGV truck drivers
      to help prioritize action aimed at risk reduction. Truck drivers (n = 192)
      completed an occupational questionnaire with two measures of vibration exposure
      (weekly hours and distance driven). Items on manual handling, relevant ergonomics
      factors and musculoskeletal problems were also included. Reported exposures to
      vibration ranged from 12 to 85 h per week, with a mean of 43.8 h. Distances
      driven ranged from 256 to 6400 km (mean 2469 km). Most of the respondents (81%)
      reported some musculoskeletal pain during the previous 12 months and 60% reported
      low back pain. Contrary to expectations, vibration exposures were significantly
      lower among those who suffered musculoskeletal symptoms when distance was used as
      an exposure measure. Manual handling and subjective ratings of seat discomfort
      were associated with reported musculoskeletal problems.

PMID- 17457744
TI  - Driver sensitivity to brake pulse duration and magnitude.
AB  - Adaptive cruise control (ACC) requires that the driver intervene in situations
      that exceed the capability of ACC. A brake pulse might provide a particularly
      compatible means of alerting the driver to situations in which the acceleration
      authority of the ACC has been exceeded. This study examined the sensitivity of
      the driver to brake pulses of five different amplitudes (0.01-0.025 g) and five
      different durations (50-800 ms). Drivers were sensitive to accelerations as low
      as 0.015 g. Pulse duration interacted with pulse amplitude, such that moderate
      duration pulses were more detectable than long and short duration pulses at
      intermediate levels of pulse amplitude. A power function with an exponent of 1.0
      accounted for 99% of the variance in drivers' sensitivity to pulse amplitude;
      however, a power function with an exponent of 0.23 accounted for only 70% of the
      variance in drivers' sensitivity to pulse duration. These results can help
      designers create ACC algorithms and develop brake pulse warnings.

PMID- 17457745
TI  - Effect of joystick stiffness, movement speed and movement direction on joystick
      and upper limb kinematics when using hydraulic-actuation joystick controls in
      heavy vehicles.
AB  - Despite the widespread use of hydraulic-actuation joysticks in mobile North
      American construction, mining and forestry vehicles, the biomechanical effects
      that joysticks have on their human operators has not been studied extensively.
      Using nine unskilled joystick operators and a laboratory mock-up with a commonly
      used North American heavy off-road equipment hydraulic-actuation joystick and
      operator seat, the purpose of this work was to quantify and compare the effects
      of three hydraulic-actuation joystick stiffnesses and two movement speeds on
      upper limb and joystick kinematics as one of the initial steps towards the
      development of a hydraulic-actuation joystick design protocol. In addition to
      providing a detailed description of the kinematics of a constrained occupational
      task, coupled with the corresponding effects of the task on operator upper limb
      kinematics, results from principal component analysis and ANOVA procedures
      revealed a number of differences in joystick and upper limb angle ranges and
      movement curve shapes resulting from the various joystick stiffness-speed
      combinations tested. For the most part, these joystick motion alterations were
      caused by small, insignificant changes in one or more upper limb joint angles.
      The two exceptions occurred for forward movements of the joystick; the fast speed
      - light stiffness condition movement pattern shape change was caused primarily by
      an alteration of the elbow flexion-extension movement pattern. Similarly, the
      fast speed - normal stiffness condition movement curve shape perturbation - was
      caused principally by a combination of significant movement curve shape
      alterations to elbow flexion-extension, external-internal shoulder rotation and
      flexion-extension of the shoulder. The finding that joystick stiffness and speed
      alterations affect joystick and upper limb kinematics minimally indicates that
      the joystick design approach of modelling the joystick and operator upper limb as
      a closed linkage system should be pursued. This approach would allow one to
      simulate the upper limb and joystick kinematics that result from virtual changes
      to upper limb and joystick lengths.

PMID- 17457746
TI  - Effects of user experience, working posture and joint hardness on powered
      nutrunner torque reactions.
AB  - Powered hand tools produce reaction forces that may be associated with upper
      extremity musculoskeletal disorders. The handle displacement, grip force and
      upper limb muscle activity (electromyography (EMG)) due to the effects of
      operator experience, working height and distance, type of tool and fastener joint
      hardness were measured in this study with 15 experienced and 15 novice nutrunner
      users. The results show that when pistol grip handles were used to work on a
      horizontal surface, experienced users allowed an average handle displacement of
      7.9 degrees, while novice users allowed 11.5 degrees. Average EMG scaled by
      reference voluntary contraction (RVC) at forearm flexors, forearm extensors and
      biceps were greater for experienced users (318% RVC, 285% RVC, 143% RVC,
      respectively) than for novice users (246% RVC, 219% RVC, 113% RVC, respectively).
      Experienced users exerted more grip force than novice users when using right
      angle handles, but less force when using pistol grip handles. The results suggest
      that it is possible to minimize tool handle displacement by adapting the
      workplace layout to permit different working postures for each user group.

PMID- 17457747
TI  - The effect of camera viewing angle on posture assessment repeatability and
      cumulative spinal loading.
AB  - Video-based task analysis in the workplace is often limited by equipment location
      and production line arrangement, therefore making it difficult to capture the
      motion in a single plane. The purpose of this study was to investigate the
      effects of camera placement on an observer's ability to accurately assess working
      postures in three dimensions and the resultant influence on the reliability and
      repeatability of calculated cumulative loading variables. Four video cameras were
      placed at viewing angles of 0 degrees, 45 degrees, 60 degrees and 90 degrees to
      the frontal plane, enabling the simultaneous collection of views of four lifting
      tasks (two symmetric and two asymmetric). A total of 11 participants were trained
      in the use of the 3DMatch 3-D posture matching software package (developed at the
      University of Waterloo) and were required to analyse 16 lifting trials. Four of
      the participants were randomly selected to return within 72 h and repeat the
      analysis protocol to test intra-observer repeatability. Posture matching
      agreement between camera views was higher when the body segments had a minimal
      range of motion during the task. There was no significant participant main
      effect; however, there was a significant (p < 0.05) task main effect. Intraclass
      correlation coefficients (ICC) were calculated to assess the between day
      reliability. Compression, reaction anterior shear and extension moment were all
      found to have excellent reliability (ICC > 0.75). Joint anterior shear and joint
      posterior shear both provided fair to good reliability (0.4 > ICC < 0.75).
      Overall, the impact of the camera viewing angle on an observer's ability to match
      working postural exposure was found to be small.

PMID- 17457748
TI  - Susceptibility to seasickness.
AB  - This paper explains part of the observed variability in passenger illness ratings
      aboard ships by gender, age and sickness history. Within the framework of a
      European project, 2840 questionnaires, gathered on several ships operating all
      over Europe, were analysed. Gender, age and sickness history all had a highly
      significant effect on seasickness. Furthermore, these effects could be
      characterized by two fixed parameters describing a general age effect, a third
      parameter dependent on sickness history and a fourth parameter dependent on
      gender. Female illness ratings peaked at an age of 11 years, 1.5 times as high as
      male ratings, which peaked at an age of 21 years. At higher ages, illness ratings
      decrease to only 20% of their maximum, reducing gender differences to zero.
      Passengers with a previous history of seasickness rated their illness about two
      times higher than those who had not felt sick before.

PMID- 17457749
TI  - Automation and decision support in interactive consumer products.
AB  - This article presents two empirical studies (n = 30, n = 48) that are concerned
      with different forms of automation in interactive consumer products. The goal of
      the studies was to evaluate the effectiveness of two types of automation:
      perceptual augmentation (i.e. supporting users' information acquisition and
      analysis); and control integration (i.e. supporting users' action selection and
      implementation). Furthermore, the effectiveness of on-product information (i.e.
      labels attached to product) in supporting automation design was evaluated. The
      findings suggested greater benefits for automation in control integration than in
      perceptual augmentation alone, which may be partly due to the specific
      requirements of consumer product usage. If employed appropriately, on-product
      information can be a helpful means of information conveyance. The article
      discusses the implications of automation design in interactive consumer products
      while drawing on automation models from the work environment.

PMID- 17457750
TI  - An epidemiological appraisal instrument - a tool for evaluation of
      epidemiological studies.
AB  - In recent years, ergonomics practices have increasingly relied upon the knowledge
      derived from epidemiological studies. In this regard, there is limited research
      devoted to the exclusive evaluation of the methodological qualities of ergonomics
      epidemiological studies. The aim of this study was to develop and test a general
      purpose 'epidemiological appraisal instrument' (EAI) for evaluating the
      methodological quality of existing or new ergonomic epidemiological studies using
      a critical appraisal system rooted in epidemiological principles. A pilot EAI
      version was developed and tested by a team of
      epidemiologists/physicians/biostatisticians, with the team leader being both
      epidemiologist and ergonomist. The pilot version was further tested with regard
      to other raters with/without a background in epidemiology, biostatistics and
      ergonomics. A revised version was evaluated for criterion validity and
      reliability. An assessor with a basic background in epidemiology and
      biostatistics would be able to correctly respond on four out of five questions,
      provided that subject matter expertise is obtained on specific items. This may
      improve with the article's quality. Training may have an effect upon assessors
      with virtually no background in epidemiology/biostatistics, but with a background
      in ergonomics. In this latter case, the inter-rater degree of agreement is
      largely above 90% and assessors can resolve their differences in a subsequent
      round. The EAI proved to be a valid and reliable appraisal instrument that may be
      used in various applications, such as systematic reviews and meta-analyses.

PMID- 17457753
TI  - Enhanced yield of chromosome aberrations after CT examinations in paediatric
      patients.
AB  - PURPOSE: To determine whether computed tomography (CT) could enhance the
      chromosome aberration yields in paediatric patients. MATERIAL AND METHODS: Blood
      samples were taken before and after CT scans from 10 children for whom the
      medical justifications for CT examinations were accidental injuries and not
      diseases as investigated in earlier studies. Chromosome analysis was carried out
      in lymphocytes by fluorescence plus Giemsa (FPG) staining exclusively in
      metaphases of the first cell cycle in vitro. RESULTS: The mean blood dose of the
      10 children was about 12.9 mGy which was determined by a newly developed dose
      estimation. Based on more than 20,000 analyzed cells it was found that after CT
      examination the frequencies of dicentrics (dic) and excess acentric fragments
      (ace) in lymphocytes were significantly increased. By subdividing the children
      into two age groups, those with an age from 0.4 years to 9 years and from 10 - 15
      years, it became obvious that the observed increase in chromosome aberrations was
      mainly contributed by the younger age group. In this group the frequency of
      dicentrics was significantly increased whereas in the older group the observed
      increase was not significant. CONCLUSION: Our results demonstrate that CT
      examinations enhance the dicentrics yields in peripheral lymphocytes of children
      aged up to 15 years. Since in particular significantly increased dicentric yields
      could be observed in children with an age from 0.4 - 9 years, it can be assumed
      that children younger than 10 years may be more radiation sensitive than older
      subjects.

PMID- 17457754
TI  - Reproductive death of cancer cells induced by femtosecond laser pulses.
AB  - PURPOSE: High intensity femtosecond (1 fs = 10(-15) s) laser pulses may, via
      multi-photon processes, cause reproductive cell death at wavelengths that
      otherwise are harmless. We study the efficacy of inducing reproductive death of
      cancer cells by ultraviolet (UV), visible (VIS) and near infrared (IR)
      femtosecond laser pulses. MATERIALS AND METHODS: Human squamous carcinoma
      cervical cancer cells are irradiated by femtosecond laser pulses at 800
      nanometers (nm), 400 nm, 266 nm and 200 nm. The reproductive death is assessed by
      colony forming assay. The contribution from multi-photon processes is evaluated
      by comparing the cell reproduction subsequent to irradiation by collimated (low
      intensity) and focused (high intensity), pulsed laser beams with identical
      fluences. RESULTS: Suitable femtosecond pulses are capable of arresting cell
      reproduction at all the tested wavelengths. Irradiation at 266 nm is far more
      efficient than the other wavelengths, both in terms of the fluence and the
      absorbed dose needed to induce reproductive cell death. The collimated 800 nm
      beam is unable to induce reproductive cell death even at a fluence of 230
      Joule/square centimeters (J/cm2). However, focused 800 nm pulses with much higher
      intensities, but lower fluences efficiently arrest cell reproduction, thus
      highlighting the dramatic effect of multi-photon processes. At the intensities
      used in the present work focusing the 400 nm beam improves its efficacy by an
      order of magnitude, whereas focusing the 266 nm beam does not improve its
      efficacy. CONCLUSION: Femtosecond pulses at 200, 266, 400 and 800 nm induce
      reproductive cell death if the intensity is sufficiently high. Multi-photon
      processes can improve the efficacy substantially and even result in reproductive
      cell death at wavelengths, where single-photon processes are harmless.

PMID- 17457755
TI  - Biological effects of protons targeted to different ranges in Arabidopsis seeds.
AB  - PURPOSE: To investigate the biological effects of radiation damage induced at
      different depths of a plant seed and to investigate the difference in radiation
      response between dry seeds and water-imbibed seeds to the same type of radiation.
      MATERIALS AND METHODS: Arabidopsis seeds of the wild-type Columbia ecotype were
      used in our experiments. Dry or water-imbibed Arabidopsis seeds were irradiated
      with 1.1 MeV, 2.6 MeV or 6.5 MeV protons (H+). For comparison, 30 keV nitrogen
      ions (N+) were also used to irradiate dry Arabidopsis seeds. The germination and
      survival rates of the seeds were measured after each irradiation. RESULTS: After
      irradiation with 2.6 MeV H+ and 6.5 MeV H+, the fluence-response curves for
      germination and survival had distinct shoulders and then survival was reduced
      rapidly with increasing fluence. 2.6 MeV H+ was more effective than 6.5 MeV H+ in
      inhibiting germination and survival and water-imbibed seeds were more sensitive
      to the 6.5 MeV H+ irradiation than dry seeds. For 1.1 MeV H+ the germination and
      survival rates were reduced gradually and an intermediate plateau emerged for
      germination, which was similar to that observed for survival following 30 keV N+
      irradiation. One of the key morphologic malformations, the multi-SAM (shoot
      apical meristem), was observed both for dry and water-imbibed seeds after all
      proton irradiations and for the dry seeds after 30 keV N+ irradiation.
      CONCLUSIONS: Radiation-induced damage produced at different ranges in Arabidopsis
      seeds results in different fluence-response curves with water-imbibed seeds being
      more sensitive to proton irradiation than dry seeds. As well as the shoot apical
      meristem (SAM) being the primary target for irradiation, there exists a secondary
      target around the SAM that also contributes to the radiation response.

PMID- 17457756
TI  - Gamma-irradiated ceruloplasmin affords antifibrillatory protection against
      ischemia/reperfusion damage in the isolated rat heart.
AB  - PURPOSE: Ceruloplasmin (CP), an important serum antioxidant, was previously found
      to reduce the incidence of ventricular fibrillation (VF) induced by ischemia and
      reperfusion in isolated rat hearts. The present study investigated whether CP
      sterilized by gamma-irradiation maintains its antiarrhythmic capacity and in
      vitro antioxidant properties. MATERIALS AND METHODS: Isolated rat hearts
      submitted to regional ischemia (15 min), were reperfused (10 min) with native CP
      or with CP irradiated at various doses (1-3 kGy) in the absence or presence of
      tyrosine (Tyr). RESULTS: All untreated hearts showed VF at reperfusion, which
      were all irreversible ventricular fibrillation (IVF). No IVF were found in hearts
      treated with native CP or gamma-irradiated CP. Cardioprotection afforded by
      irradiated CP (with or without Tyr) was slightly higher than that obtained with
      native CP. No VF at all (100% prevention) was found in hearts treated with CP
      irradiated alone or in the presence of tyrosine at 3 kGy. Tyrosine and irradiated
      tyrosine had no cardiotoxic or protective effects on reperfusion-induced
      arrhythmias. The Oxygen Radical Absorbing Capacity (ORAC), measured in vitro with
      beta-phycoerythrin (beta-PE) fluorescent indicator, was slightly higher for gamma
      irradiated CP in the presence of Tyr. CONCLUSIONS: Ceruloplasmin sterilized by
      gamma-irradiation maintains antioxidant and antiarrhythmic effects in the post
      ischemia reperfused isolated rat heart.

PMID- 17457757
TI  - Kinetics and dose-response of residual 53BP1/gamma-H2AX foci: co-localization,
      relationship with DSB repair and clonogenic survival.
AB  - PURPOSE: Recent studies revealed that some foci produced by phosphorylated
      histone 2A family member X (gamma-H2AX) and tumor suppressor p53 binding protein
      1 (53BP1) that co-localize with radiation-induced DNA double-strand breaks (DSB)
      remain in cells at relatively long times after irradiation and indicated a
      possible correlation between cellular radiosensitivity and residual foci. In this
      study, we investigated dose-responses and kinetics for radiation-induced
      53BP1/gamma-H2AX foci formation in relation to their co-localization, DSB repair
      and cell survival. MATERIALS AND METHODS: Cell survival, DSB and foci were
      analyzed by clonogenic assay, pulsed field gel electrophoresis (PFGE), and
      confocal laser microscopy, respectively, in normal human fibroblasts (VH-10) and
      in a cancer cell line (HeLa). Computer analysis was used to determine both the
      number and the area of foci. RESULTS: We show that even at doses down to 1 cGy a
      statistically significant induction of 53BP1 foci is observed. While the number
      of foci was found to constantly decrease with post-irradiation time, the per-cell
      normalized area of foci does not change within a time window of approximately 4 h
      post-irradiation. Co-localization of gamma-H2AX and 53BP1 foci is shown to depend
      on dose and post-irradiation time. No clear correlations were established between
      radiosensitivity and foci formation because the dose response for 53BP1/gamma
      H2AX foci may depend on time after irradiation and duration of the cell cycle. We
      show that the kinetics of foci disappearance within 24 h post-irradiation do not
      coincide with those of DSB repair. CONCLUSIONS: The data suggest that the post
      irradiation time used for estimation of radiosensitivity at therapeutically
      relevant low doses (e.g., <3 Gy) in proliferating cells by scoring residual foci
      should be limited by the duration of the cell cycle, and that direct comparison
      of the kinetics of DSB repair and disappearance of DSB-co-localizing foci is not
      possible. Therefore, results obtained from the counting of foci should be
      interpreted with caution in terms of DSB repair.

PMID- 17457758
TI  - Response of chronic hypoxic cells to low dose-rate irradiation.
AB  - PURPOSE: Compare the sensitivity of human cells in vitro to low dose-rate
      irradiation in air and in moderate hypoxia (4% O2). MATERIALS AND METHODS:
      Continuous low dose-rate beta-irradiation at a dose rate of 0.015 or 0.062 Gy/h
      was given to human T-47D breast cancer cells by incorporation of [3H] -labelled
      valine into cellular protein. Acute irradiation at a dose rate of 0.4 Gy/min was
      performed using [137Cs]gamma-irradiation. Cells were cultivated in an atmosphere
      with 4% O2 using an INVIVO2 hypoxia cabinet. RESULTS: When grown in ambient air
      with continuous irradiation, T-47D cells were able to continue growth for at
      least 23 weeks at a dose-rate of 0.015 Gy/h with a surviving fraction stabilized
      at around 60%. When the dose rate was increased to 0.062 Gy/h the cell culture
      died out after about 23 days (corresponding to about 22 Gy). When grown in an
      atmosphere with 4% O2 we surprisingly found that the continuously irradiated T
      47D cells (0.015 Gy/h) were severely inhibited in their growth, and cell death
      became extensive after about 3 weeks while un-irradiated cells continued growth
      seemingly unaffected by this low oxygenation. Peri cellular oxygenation varied
      between 4% and below 0.1% over an ordinary passage due to diffusion-limitations
      through the 2 mm deep medium. Online O2-recordings over a whole passage showed
      that oxygen was more depleted in the irradiated compared to the un-irradiated
      cultures indicating increased respiration during irradiation. While cells growing
      attached to the bottom were inhibited and inactivated during irradiation it was
      found that cells attached high up in the neck region, i.e., having only a shallow
      layer of medium above them, survived and formed colonies. When cells cultivated
      in 4% O2 for 7 weeks were irradiated with acute doses of 137Cs gamma-rays, the
      radiosensitivity was the same as for cells cultivated in ambient air. CONCLUSION:
      Continuous irradiation with 0.015 Gy/h for several weeks results in a stronger
      inhibition for T-47D cells grown in an atmosphere with 4% as compared to 20% O2.
      The data indicate that this may be due to increased oxygen consumption resulting
      in more severe hypoxia in [3H]-incorporating compared to control (un-irradiated)
      cells.

PMID- 17457759
TI  - Influence of glutathione on the induction of chromosome aberrations, delay in
      cell cycle kinetics and cell cycle regulator proteins in irradiated mouse bone
      marrow cells.
AB  - PURPOSE: Reduced glutathione (GSH) is an endogenous thiol and has long been
      thought to affect the sensitivity of cells to radiation. The aim was to see the
      influence of GSH on: (i) the production of all types of radiation-induced
      chromosome aberrations (CA), and (ii) the radiation-induced delay in cell cycle
      and the levels of cell cycle regulator proteins. MATERIALS AND METHODS: Cell
      cycle kinetics were determined by scoring the mitotic index (MI). CA and MI were
      scored in gamma-irradiated buthionine sulfoximine (BSO) (10 h) or GSH (1 h)
      pretreated and untreated mouse bone marrow cells (BMC). The expression of p53 and
      p21 proteins after 2 and 6 h of irradiation and for the B-cell lymphoma 2 (Bcl-2)
      associated X-protein (Bax) after 24 h of irradiation with or without BSO or GSH
      treatment was analyzed by immunoblotting. RESULTS: Radiation delays mouse BMC in
      their passage through the cell cycle and induces CA. Exogenous addition of GSH
      protected CA uniformly at lower doses of radiation but differentially at higher
      doses, whereas GSH-depletion by BSO increased the frequency of radiation-induced
      CA. Both GSH and BSO-pretreated cells reduced the delay in cell kinetics after
      irradiation. Levels of both p53 and p21 were enhanced after irradiation to BSO
      pretreated cells. However, in GSH-pretreated cells the level of these proteins
      was reduced. CONCLUSION: Data indicate that the induction of CA and delay in cell
      kinetics by radiation may not always be interlinked and that the level of
      endogenous GSH exerts its influence on these parameters. Both GSH and BSO
      pretreatment reduce delays in cell kinetics of irradiated cells which may die
      apoptotically, since they have either a higher frequency of exchange aberrations
      or CA, respectively.

PMID- 17457762
TI  - Combined endovascular laser plus ambulatory phlebectomy for the treatment of
      superficial venous incompetence: a 4-year perspective.
AB  - BACKGROUND: Combination endovascular laser obliteration of the greater saphenous
      vein in conjunction with ambulatory phlebectomy has become the treatment of
      choice for superficial venous incompetence. OBJECTIVES: The present study
      examines the treatment of saphenofemoral junction (SFJ) incompetence with
      simultaneous treatment of associated truncal varicosities by ambulatory
      phlebectomy. METHODS: Four-year follow-up data for recurrence rate and
      complication profile was ascertained for 90 patients (mean age 40 years) with SFJ
      reflux associated with greater saphenous vein (GSV) incompetence (4-12 mm; mean
      7.8 mm) and enlargement of branch varicosities as documented by Duplex
      ultrasound, which were treated with a combined approach of endovascular laser
      obliteration of the GSV (810 nm, Diomed S30) followed by hook avulsion
      (ambulatory phlebectomy) of the remaining truncal varicosities. Follow-up by
      Duplex ultrasound to ensure closure was carried out at week 1 and months 1, 3, 6,
      12, 24, 36 and 48. RESULTS: A total recurrence rate (r = 94 limbs) of 4.3 was
      found in the patient cohort. All recurrences occurred within 12 months, with the
      majority documented at month 6. CONCLUSIONS: Combination endovascular laser
      treatment (EVLT) with ambulatory phlebectomy is an effective treatment modality
      for superficial venous incompetence in the outpatient ambulatory setting. Low
      recurrence rates are noted with this approach. In the present patient series, all
      recurrences were noted within 12 months of the aforementioned procedure. These
      results are comparable with other endovenous and radiofrequency technologies.

PMID- 17457763
TI  - The current role of laser/light sources in the treatment of male and female
      pattern hair loss.
AB  - Over the past several years there has been great interest in the potential role
      of laser/light-based treatments for male and female pattern hair loss. Despite
      aggressive marketing and centers claiming great success in the treatment of hair
      loss there is little scientific data supporting laser/light sources in hair loss.
      This paper is a consensus of hair loss experts on the current scientific data,
      mechanisms of action, safety, protocols and recommendations regarding laser/light
      treatment for hair loss. The authors believe that, while seemingly safe, there
      are no controlled, peer-reviewed studies validating current devices for hair loss
      and that all patients should be medically evaluated for any hair loss by a
      physician specialist to rule out other underlying medical conditions or the
      etiology of hair loss.

PMID- 17457764
TI  - Treatment of skin laxity of the lower face and neck in older individuals with a
      broad-spectrum infrared light device.
AB  - BACKGROUND: Non-ablative approaches with infrared and radiofrequency energy
      sources have been shown to reduce skin laxity, but studies have focused on
      individuals with early-stage, mild-to-moderate degenerative dermal changes.
      OBJECTIVE: The purpose of this prospective study was to evaluate the safety and
      efficacy of an infrared light device for the treatment of skin laxity in patients
      with soft tissue ptosis of the lower face and neck characteristic of the sixth
      decade of life and beyond. MATERIALS AND METHODS: Thirteen females, aged 58-83
      years old (average: 64 years), were treated with a filtered 1100-1800 nm infrared
      light-based device. All individuals presented with ptotic soft tissue, but varied
      in the extent of skin laxity from no visible laxity to having pendulous excess
      skin. Two treatment sessions were provided at monthly intervals. The individuals
      returned for follow-up visits at 1, 3 and 6 months after the second treatment.
      Twelve of the individuals completed the study. RESULTS: Changes were dramatic for
      those individuals in whom the skin envelope appeared to drape separately from
      deeper soft tissue. No treatment complications were noted. CONCLUSION: Infrared
      light source-induced skin tightening may be induced even in older individuals.

PMID- 17457766
TI  - Abstracts of the British Maternal and Fetal Medicine Society 12th Annual
      Conference. Belfast, United Kingdom. April 17-18, 2007.

PMID- 17457772
TI  - [Critical illness polyneuropathy and myopathy. Pathogenesis and diagnostic].
AB  - Since the first description of Bolton et al., critical illness polyneuropathy
      (CIP) and critical illness myopathy (CIM) are increasingly observed as a
      complication in intensive care patients. CIP and CIM commonly occur in patients
      with an ICU length of stay exceeding one week. Typically, these patients show
      weakness of the limbs and difficulties in weaning from the respirator.
      Neurological and electrophysiological examinations as well as muscle biopsies if
      myopathy is of concern may help to characterize and identify polyneuropathy and
      myopathy.

PMID- 17457773
TI  - [Lumbar discogenic pain. Disk degeneration and minimally invasive interventional
      therapies].
AB  - Discogenic pain has been responsible for a countless number of missed workdays
      and millions if not billions of dollars of lost revenue. Minimally invasive
      interventional therapies of the discogenic back pain gained significant
      acceptance among the proceduralists. The centuries old dilemma of discogenic low
      back pain has by no means been answered. We know today that discogenic low back
      pain has a multitude of causes. The leaking "chemical soup" within the nucleus
      pulposus is certainly responsible for causing inflammation and thus pain.
      However, neuropeptides released from peripheral endings of nociceptive afferents
      are also inflammatory mediators and pain generators. The nerves innervating the
      discs have been identified and in many cases denervated with good results. These
      nerves from posterior to anterior include the sinuvertebral nerve, the rami
      communicantes, and the sympathetic trunk. Diagnosing discogenic low back pain is
      the key to successful treatment. Classically this should be a low back pain in a
      "band-like" distribution without radiculopathy that is worse in the morning,
      worse with Valsalva, and aggravated by standing in flexion. Provocative
      discography with manometric monitoring is essential in aiding the diagnosis. Once
      the diagnosis is confirmed, a multitude of invasive therapy may be offered
      including: L2 root sleeve blocks, intradiscal RFTC, RFTC of the rami
      communicantes, or Comparative data on the effectiveness of the above-mentioned
      procedures is lacking and may in fact be an excellent topic for future
      discussion.

PMID- 17457774
TI  - [Intraoperative blood transfusion in a child with blunt abdominal trauma].
AB  - Pediatric transfusion therapy is complex since there is a remarkable
      physiological change from neonate to child. Here we report the blood transfusion
      management of a 6-year-old male child after abdominal trauma. Particular
      normovolemia with ringer/hetastarch, the estimation of the maximal allowable
      blood loss, target transfusion hematocrit, transfusion with platelets and FFP are
      discussed.

PMID- 17457775
TI  - [Palliative medicine. Self determination and care at life's end].

PMID- 17457776
TI  - ["It is a longer path to death !" On the way with palliative medicine].

PMID- 17457777
TI  - [State of the art 2007].
AB  - The beginning of the modern hospice movement and palliative medicine relates to
      the recognition of the fact that a cure-oriented health care system often
      neglects the critically ill and the dying in terms of appropriate treatment and
      human care. Therefore, the idea was born to offer comprehensive medical, nursing,
      psychological, social and spiritual care for these patients and their families at
      a suitable location . This first location was St Christopher's Hospice in London;
      the starting point of a still ongoing humanly and ethically demanded development.

PMID- 17457778
TI  - [Symptom relief in terminal illness].
AB  - It is the goal of palliative care to provide as large a relief of the disease
      symptoms as possible for patients, who are incurably sick, in order to improve
      the quality of the remaining life. Some of the symptoms can hardly be treated;
      others like pain, dyspnea, gastrointestinal complaints or sweating can usually be
      well alleviated. The condition for this is a careful evaluation of the clinical
      status before the treatment, in order to reach symptom relief by purposeful
      actions without new side effects.

PMID- 17457779
TI  - [Multiprofessional cooperation in palliative care].
AB  - "Nothing is more powerful than an idea whose time has come." (Victor Hugo)
      Originally referring to the beginning of the enlightenment (reconnaissance) of
      the French revolution the transcription of this words regarding to German
      palliative Care structures would mean a tremendous effort. The meaning of the new
      idea is a holistic kind of care for patients with a chronic disease at the end of
      their lives, so that they can die as most self determined as possible at a
      location of their choice. The special aim of palliative care, the need of
      interdisciplinary cooperation leading to multidisciplinary solutions is pointed
      out. The meaning of palliative care team as a team with special communication
      skills in between the team and with further cooperating partners is described.
      Communication in palliative care means more than telling facts.

PMID- 17457780
TI  - [Epidemiology of primary drug resistance in chronically HIV-infected patients in
      Nordrhein-Westfalen, Germany, 2001-2005].
AB  - BACKGROUND AND OBJECTIVE: Primary HIV drug resistance, characterized by mutant
      virus strains in untreated HIV-infected persons, is of significant
      epidemiological significance. Primary resistance is associated with reduced
      efficacy of antiretroviral therapy (ART). We determined the prevalence of primary
      resistance in Nordrhein-Westfalen, Germany. PATIENTS AND METHODS: Genotypic
      resistance testing was performed in a prospective multicenter study in
      chronically infected previously untreated HIV-positive patients before
      administration of first-line ART. Mutations were classified according to the
      International AIDS Society USA guidelines and the geno2pheno interpretation tool.
      RESULTS: Between January 2001 and December 2005, resistance testing was performed
      in 831 patients. 77.4% were males, the mean age was 39 years (SD: 10.5). The mean
      duration of diagnosis of HIV infection was 1.6 years (SD: 3.4). 32.4% of patients
      were at CDC stage C, mean CD4 cell count was 236 /microl (SD: 205), and mean
      viral load was 206,855 copies/ml (SD: 450,610). In total, resistance-associated
      mutations were detected in 75 patients (9.0%; 95%CI, 7.1-11.0). After inclusion
      of mutations E44D and V118I, resistance was identified in 99 patients (11.9%;
      95%CI, 9.7-14.1). 5.4% had mutations indicating nucleoside reverse transcriptase
      inhibitor (NRTI) resistance (95%CI, 3.9-7.0), 3.0% had non-NRTI resistance
      (95%CI, 1.8-4.2), and 2.4% had protease inhibitor resistance (95%CI, 1.4-3.4),
      respectively. Two-class resistance was detected in 0.8% (95%CI, 0.2-1.5), three
      class resistance in 0.5% (95%CI, 0.01-1.0). Mutations indicating revertant
      variants of resistant strains were found in 3.9% (95%CI, 2.5-5.2). Considering
      the variables age, gender, time since diagnosis, CDC stage, CD4 cell count, viral
      load, HIV subtype, ethnic origin, and HIV transmission group, no significant risk
      factor for the presence of primary resistance was demonstrated in univariate and
      mutlivariate analyses. CONCLUSION: The prevalence of primary resistant virus
      strains was about 10% in chronically infected ART-naive HIV-patients in the
      largest federal state of Germany. The majority of these patients had NRTI
      associated resistance. No risk factor for the presence of primary drug resistance
      was identified. Because of the high prevalence and the possible impact on
      efficacy of drug treatment, routine genotypic resistance testing should be
      performed in untreated HIV-positive patients before administration of first-line
      ART.

PMID- 17457782
TI  - [Iliac thrombus with peripheral embolization].

PMID- 17457781
TI  - [Graves' disease and papillary thyroid cancer--coincidence or association?].
AB  - HISTORY AND ADMISSION FINDINGS: A 41-year-old woman presented with hyperhydrosis,
      tremor, restlessness, sleeplessness and diarrhea. She had a tachycardia and later
      she developed soreness of her conjunctives. A tender goitre could be palpated.
      INVESTIGATIONS: Laboratory results showed thryeotoxicosis and later elevated
      TRAK. Ultrasound revealed a thyroid nodule. Scintigraphic uptake was generally
      elevated. Graves disease was diagnosed. TREATMENT AND COURSE: After 12 months of
      thyreostatic medication recurrence occurred and a thyroidectomy was performed.
      Histologically a papillary cancer was found and postoperative radioiodinetherapy
      was added. CONCLUSION: Due to leading symptoms of thyreotoxicosis the thyroid
      nodule has preoperatively not been paid enough attention to. A pathophysiologic
      association of Graves disease and differentiated thyroid cancer is controversely
      discussed but seems possible considering present literature data.
      Scintigraphically "cold" nodules in graves disease, as in simple nodular goitre,
      have a higher probability of malignancy.

PMID- 17457783
TI  - [Allergies and parasites].

PMID- 17457784
TI  - [Practical guidelines for the management of osteoporosis--evidence-based and cost
      effective].

PMID- 17457785
TI  - [Of desk-economists and doctors at the bedside within a health care system: they
      should learn from each other].

PMID- 17457786
TI  - [Patient's right to examine medical records].

PMID- 17457788
TI  - [In-hospital mortality of acute hemorrhage of esophageal/fundus varices: an
      analysis of blood glucose level and other risk factors in 99 consecutive
      patients].

PMID- 17457789
TI  - Formation of potentially prebiotic amphiphiles by reaction of beta-hydroxy-n
      alkylamines with cyclotriphosphate.

PMID- 17457790
TI  - Measurement of 1H-1H residual dipolar coupling constants for structural studies
      of medium size molecules.
AB  - Residual dipolar coupling constants (RDCs) are being increasingly applied to
      elucidate the configuration and conformation of small organic molecules, peptides
      and oligosaccharides. In this paper we describe a set of robust 1D NMR methods
      for accurate and precise measurement of proton-proton RDCs of small and medium
      size molecules. The performance of these techniques is not impeded by the
      presence of overlapping and broad (1)H multiplets that are typically observed for
      such molecules in weakly aligned media. The use of these techniques provides
      access to a large pool of proton-proton RDCs opening new avenues for the solution
      structure elucidation of medium size molecules by NMR. The techniques are
      illustrated on the determination of the alignment tensor of the reducing
      monosaccharide ring of cellobiose and the determination of the relative
      configuration of sodium cholate.

PMID- 17457792
TI  - Synthesis, structural characterization, electronic structure, and magnetic
      properties of the Zintl phase Eu10Cd6Bi12.
AB  - A new transition-metal-containing Zintl phase, Eu(10)Cd(6)Bi(12), was synthesized
      by combining the elements in excess molten Cd. Single-crystal X-ray diffraction
      studies indicated that this compound crystallizes in the orthorhombic space group
      Cmmm (No. 65) with a=7.840(2), b=24.060(7), and c=4.7809(14) A. The crystal
      structure of Eu(10)Cd(6)Bi(12) can be viewed as a stacking of a series of
      [Cd(6)Bi(12)] double layers, which are arranged alternately along the b axial
      direction. The layers are composed of corner- and edge-shared CdBi(4) tetrahedra,
      a common feature in the crystal chemistry of many transition-metal Zintl phases.
      Electronic-band-structure calculations confirm the closed-shell configuration of
      all constituent elements and corroborate the electron count inferred by the Zintl
      formalism, that is, [Eu(2+)](10)[Cd(2+)](6)[Bi(3-)](8)[Bi(2-)](4). Magnetic
      susceptibility measurements confirm the divalency of europium and show the
      existence of a long-range antiferromagnetic order of the Eu spins below 12.3 K.

PMID- 17457791
TI  - Modern potentiometry.
AB  - For most chemists, potentiometry with ion-selective electrodes (ISEs) primarily
      means pH measurements with a glass electrode. Those interested in clinical
      analysis might know that ISEs, routinely used for the determination of blood
      electrolytes, have a market size comparable to that of glass electrodes. It is
      even less well known that potentiometry went through a silent revolution during
      the past decade. The lower detection limit and the discrimination of interfering
      ions (the selectivity coefficients) have been improved in many cases by factors
      up to 10(6) and 10(10), respectively, thus allowing their application in fields
      such as environmental trace analysis and potentiometric biosensing. The
      determination of complex formation constants for lipophilic hosts and ionic
      guests is also covered in this Minireview.

PMID- 17457793
TI  - Effects of combined intervention programmes for people with dementia living at
      home and their caregivers: a systematic review.
AB  - OBJECTIVE: This study reviews the evidence for effects of combined intervention
      programmes for both the informal caregiver and the person with dementia. METHOD:
      Systematic review. Electronic databases and key articles were searched for effect
      studies of combined programmes, published between January 1992 and February 2005.
      The resulting 52 reports were scored according to set inclusion criteria.
      RESULTS: Twenty five reports relating to 22 programmes met the inclusion
      criteria. Various aspects of caregivers' mental health and burden were studied.
      Best results were obtained regarding general mental health. Other aspects often
      showed modest and varying results. Caregivers' competence was less often
      addressed. The effects on the cognitive and physical functioning, behavioural
      problems and survival of the persons with dementia were modest and inconsistent,
      whereas their mental health is positively affected and admittance to long stay
      care is often delayed. CONCLUSION: Combined programmes may improve some, not all,
      aspects of functioning for caregiver and person with dementia. Care professionals
      must define their programme goals and target groups before advising their clients
      on a combined programme. Research may focus on the effects of programmes that
      were introduced fairly recently and on subgroups of caregivers (female
      caregivers, depressed caregivers and people with dementia, and minorities).

PMID- 17457794
TI  - Characteristics and quality of adverse drug reaction reports by pharmacists in
      Norway.
AB  - PURPOSE: To evaluate the characteristics and quality of adverse drug reaction
      (ADR) reports submitted by pharmacists, and thereby assess the possible
      contribution of pharmacists to the spontaneous reporting system for ADRs in
      Norway. METHODS: An open, prospective study was conducted where dispensing
      pharmacists from 39 pharmacies were encouraged to report ADRs over a 3-month
      period. The submitted ADR reports were compared to reports by physicians from the
      same time period. All reports were evaluated for selected characteristics, that
      is distribution of Anatomical Therapeutic Chemical (ATC) classification codes of
      suspected drugs, distribution of ADRs according to system-organ classes and the
      quality of the reports. RESULTS: A total of 118 reports covering 274 ADRs
      received from the pharmacists were compared to 109 ADR reports with 304 ADRs
      submitted by physicians. Pharmacists more often reported ADRs related to
      cardiovascular drugs, alimentary tract and metabolism drugs and respiratory
      drugs, whereas physicians more frequently reported ADRs related to
      musculoskeletal drugs and antineoplastic and immunomodulating agents. ADRs
      reported by pharmacists more frequently described gastrointestinal reactions
      while physicians reported more ADRs in relation to the cardiovascular and blood
      system. Whereas 68% of the physicians' reports were classified as serious, only
      5% of the pharmacists' reports were serious. More than 50% of the reports
      submitted by pharmacists concerned ADRs following a generic substitution, in
      contrast to only 2% of the physicians' reports. The pharmacists' reports were
      found to be of a lower documentation grade. However, there was no substantial
      difference in a subjective assessment of the quality of information in the
      reports submitted by the two categories of health professionals. CONCLUSIONS:
      Pharmacists submit valuable ADR reports which provide information complimentary
      to physicians' reports. This emphasises that pharmacist ADR reporting might
      constitute an important addition to the spontaneous reporting system.

PMID- 17457795
TI  - Encoding of electrophysiology and other signals in MR images.
AB  - PURPOSE: To develop a gradient insensitive, generic technique for recording of
      non-MR signals by use of surplus scanner bandwidth. MATERIALS AND METHODS:
      Relatively simple battery driven hardware is used to transform one or more
      signals into radio waves detectable by the MR scanner. Similar to the "magstripe"
      technique used for encoding of soundtracks in motion pictures, the electrical
      signals are in this way encoded as artifacts appearing in the MR images or
      spectra outside the region of interest. The encoded signals are subsequently
      reconstructed from the signal recorded by the scanner. RESULTS:
      Electrophysiological (EP) eye and heart muscular recording (electrooculography
      [EOG] and electrocardiography [ECG]) during fast echo planar imaging (EPI) is
      demonstrated with an expandable, modular 8-channel prototype implementation. The
      gradient artifacts that would normally be dominating EOG are largely eliminated.
      CONCLUSION: The method provides relatively inexpensive sampling with inherent
      microsecond synchronization and it reduces gradient artifacts in physiological
      recordings significantly. When oversampling is employed, the method is compatible
      with all MR reconstruction and postprocessing techniques.

PMID- 17457796
TI  - Detection of myocarditis by contrast-enhanced MRI in patients presenting with
      acute coronary syndrome but no coronary stenosis.
AB  - PURPOSE: To prospectively assess the use of cardiac MRI with delayed contrast
      enhancement (DCE) for identifying patients with active myocarditis among those
      presenting with acute coronary syndrome (ACS) but no coronary stenosis. MATERIALS
      AND METHODS: A total of 27 consecutive patients (age = 45 +/- 17 years; 14 male)
      presenting with ACS (chest pain, positive troponin-I) and no coronary stenosis,
      underwent cardiac MRI 9 +/- 7 days after pain onset and 8 +/- 5 months later (N =
      19). Steady-state free-precession pulse (SSFP) sequence was applied for the
      assessment of myocardial function and both inversion-recovery (IR) and SSFP
      sequences were used for analyzing the topography and extent of DCE areas. Rest
      sestamibi-gated-single photon emission CT (SPECT) was also systematically
      performed. RESULTS: Subepicardial DCE pattern typical of acute myocarditis was
      documented in 12 patients (44%). Ischemic DCE pattern (transmural or
      subendocardial focal DCE) was documented in 12 of the 15 remaining patients
      (44%). Patients with subepicardial DCE had: higher C-reactive protein (CRP)
      levels (38 +/- 32 vs. 14 +/- 24 mg/mL; P = 0.04), lower Framingham cardiovascular
      risk (3 +/- 3% vs. 9 +/- 5%; P < 0.001), lower incidence of perfusion SPECT
      defects (17% vs. 73%; P = 0.01), higher left ventricular (LV) end-diastolic
      volume (77 +/- 16 vs. 64 +/- 10 mL/m(2); P = 0.02), and higher regression of DCE
      areas at follow-up (-65 +/- 17% vs. -18 +/- 23%; P = 0.002). CONCLUSION: DCE
      pattern of active myocarditis can be seen in patients presenting with ACS but no
      coronary stenosis.

PMID- 17457797
TI  - Assessing normal pulse wave velocity in the proximal pulmonary arteries using
      transit time: a feasibility, repeatability, and observer reproducibility study by
      cardiovascular magnetic resonance.
AB  - PURPOSE: To calculate pulse wave velocity (PWV) in the proximal pulmonary
      arteries (PAs) by cardiovascular magnetic resonance (CMR) using the transit-time
      method, and address respiratory variation, repeatability, and observer
      reproducibility. MATERIALS AND METHODS: A 1.9-msec interleaved phase velocity
      sequence was repeated three times consecutively in 10 normal subjects. Pulse wave
      (PW) arrival times (ATs) were determined for the main and branch PAs. The PWV was
      calculated by dividing the path length traveled by the difference in ATs.
      Respiratory variation was considered by comparing acquisitions with and without
      respiratory gating. RESULTS: For navigated data the mean PWVs for the left PA
      (LPA) and right PA (RPA) were 2.09 +/- 0.64 m/second and 2.33 +/- 0.44 m/second,
      respectively. For non-navigated data the mean PWVs for the LPA and RPA were 2.14
      +/- 0.41 m/second and 2.31 +/- 0.49 m/second, respectively. No statistically
      significant difference was found between respiratory non-navigated data and
      navigated data. Repeated on-table measurements were consistent (LPA non-navigated
      P = 0.95, RPA non-navigated P = 0.91, LPA navigated P = 0.96, RPA navigated P =
      0.51). The coefficients of variation (CVs) were 12.2% and 12.5% for intra- and
      interobserver assessments, respectively. CONCLUSION: One can measure PWV in the
      proximal PAs using transit-time in a reproducible manner without respiratory
      gating.

PMID- 17457798
TI  - Patient motion correction for multiplanar, multi-breath-hold cardiac cine MR
      imaging.
AB  - PURPOSE: To correct for spatial misregistration of multi-breath-hold short-axis
      (SA), two-chamber (2CH), and four-chamber (4CH) cine cardiac MR (CMR) images
      caused by respiratory and patient motion. MATERIALS AND METHODS: Twenty CMR
      studies from consecutive patients with separate breath-hold 2CH, 4CH, and SA 20
      phase cine images were considered. We automatically registered the 2CH, 4CH, and
      SA images in three dimensions by minimizing the cost function derived from plane
      intersections for all cine phases. The automatic alignment was compared with
      manual alignment by two observers. RESULTS: The processing time for the proposed
      method was <20 seconds, compared to 14-24 minutes for the manual correction. The
      initial plane displacement identified by the observers was 2.8 +/- 1.8 mm
      (maximum = 14 mm). A displacement of >/=5 mm was identified in 15 of 20 studies.
      The registration accuracy (defined as the difference between the automatic
      parameters and those obtained by visual registration) was 1.0 +/- 0.9 mm, 1.1 +/-
      1.0 mm, 1.1 +/- 1.2 mm, and 2.0 +/- 1.8 mm for 2CH-4CH alignment and SA alignment
      in the mid, basal, and apical regions, respectively. The algorithm variability
      was higher in the apex (2.0 +/- 1.9 mm) than in the mid (1.4 +/- 1.4 mm) or basal
      (1.2 +/- 1.2 mm) regions (ANOVA, P < 0.05). CONCLUSION: An automated
      preprocessing algorithm can reduce spatial misregistration between multiple CMR
      images acquired at different breath-holds and plane orientations.

PMID- 17457799
TI  - Multiple regression method for pulmonary apparent diffusion coefficient
      measurement by hyperpolarized 3He MRI.
AB  - PURPOSE: To develop and validate a new multiple regression technique for the
      separation of flip angle effect in pulmonary apparent diffusion coefficient (ADC)
      measurement. MATERIALS AND METHODS: Hyperpolarized (3)He MRI (HP (3)He MRI) ADC
      measurements were performed on phantom, pig, and human models. The diffusion
      sensitization sequence is modified from a standard gradient echo (GRE) sequence
      with a nonlinear progression in the bipolar gradient amplitude with each image.
      In the self-diffusion phantom experiment, four images were acquired with base
      gradient factor b(0) = 0.15 second/cm(2); in the pig and human experiment, six
      images were acquired with base gradient factor b(0) = 1.4 second/cm(2). RESULTS:
      The self-diffusion coefficient measured in the phantom experiment was 1.98 +/-
      0.16 cm(2)/second. The measured uncertainty curve was consistent with the
      theoretically predicted curve. The measured in vivo ADC values (three coronal
      slices in the supine direction) were 0.20/0.16/0.13 cm(2)/second and
      0.20/0.18/0.16 cm(2)/second for pig and human experiments, respectively.
      CONCLUSION: With the introduction of a nonlinear progression in the diffusion
      sensitization gradients, the multiple regression technique is capable of
      separating the flip angle effect in ADC measurement. In addition, this technique
      can perform a rigorous measurement uncertainty analysis and provide the optimal
      scan parameters that yield best noise performance.

PMID- 17457800
TI  - A simple catheter-vessel model for MR assessment of drug distribution in arteries
      and optimization of catheter design for intraarterial infusion therapy.
AB  - PURPOSE: To investigate the efficacy of a new catheter-vessel model for MRI to
      evaluate drug distribution and to optimize catheter design for intraarterial
      infusion therapy MATERIALS AND METHODS: The model consisted of a hepatic artery
      simulant tube through which blood simulant water flowed continuously and a water
      cistern. Catheters were inserted into the tube and a gadolinium contrast medium
      was injected at rates suitable for angiographic or computed tomographic
      evaluation and commensurate with the clinical drug infusion rate. Axial images of
      the tube were obtained with a 0.2-T scanner and gradient echo technique.
      Preliminary studies and catheter tests were conducted. The points at which drug
      and water were completely mixed were defined as the site with uniform enhancement
      nearest the catheter tip. RESULTS: Flip angle and gadolinium concentrations were
      optimized at 90 degrees, and at 62.5 and 500 mM for the high and low infusion
      rates, respectively. Drug distribution near the catheter tips was clearly
      visualized. The drug was mixed in shorter distances via the slit side-hole than
      the end- or side-hole catheters, and the smaller diametrical than the larger at
      either rate. CONCLUSION: This model appeared to be effective for evaluation of
      drug distribution and optimization of catheter design.

PMID- 17457801
TI  - Optimal acquisition orders of diffusion-weighted MRI measurements.
AB  - PURPOSE: To propose a new method to optimize the ordering of gradient directions
      in diffusion-weighted MRI so that partial scans have the best spherical coverage.
      MATERIALS AND METHODS: Diffusion-weighted MRI often uses a spherical sampling
      scheme, which acquires images sequentially with diffusion-weighting gradients in
      unique directions distributed isotropically on the hemisphere. If not all of the
      measurements can be completed, the quality of diffusion tensors fitted to the
      partial scan is sensitive to the order of the gradient directions in the scanner
      protocol. If the directions are in a random order, then a partial scan may cover
      some parts of the hemisphere densely but other parts sparsely and thus provide
      poor spherical coverage. We compare the results of ordering with previously
      published methods for optimizing the acquisition in simulation. RESULTS: Results
      show that all methods produce similar results and all improve the accuracy of the
      estimated diffusion tensors significantly over unordered acquisitions.
      CONCLUSION: The new ordering method improves the spherical coverage of partial
      scans and has the advantage of maintaining the optimal coverage of the complete
      scan.

PMID- 17457802
TI  - Assessment of the carotid artery by MRI at 3T: a study on reproducibility.
AB  - PURPOSE: To examine the reproducibility of carotid artery dimension measurements
      using 3T MRI. MATERIALS AND METHODS: Ten healthy volunteers underwent three scans
      on two occasions for assessment of total vessel wall area (TVWA), total luminal
      area (TLA), and minimum (MinT) and maximum (MaxT) vessel wall thickness. A double
      inversion-recovery (IR) fast gradient-echo (FGRE) sequence was used on a
      commercial 3T system. During the first visit the subjects were scanned twice. The
      third scan was performed at least four days later. One observer traced all scans,
      and a second observer retraced the first scan series. RESULTS: For TVWA an
      interclass correlation (ICC) of 0.994 was calculated with all three scans taken
      into account. The interobserver ICC was 0.984. The agreement between the scans
      for TLA showed an ICC of 0.982 with an interobserver ICC of 0.998. For MinT and
      MaxT an ICC of 0.843 and 0.935 were calculated, with interobserver ICCs of 0.860
      and 0.726, respectively. CONCLUSION: With the use of a commercial 3T MR system,
      TVWA, TLA, and wall thickness measurements of the carotid artery can be assessed
      with good reproducibility.

PMID- 17457803
TI  - MR contrast agents: physical and pharmacologic basics.
AB  - Since approval of the first magnetic resonance (MR) contrast agent was granted in
      1988, there has been remarkable growth in the utilization of intravenous
      gadolinium (Gd)-based agents. Currently it is estimated that nearly half of all
      MR studies performed are contrast-enhanced. Despite containing a toxic heavy
      metal, these agents have proven to be not only an effective diagnostic adjunct to
      non-enhanced MRI, but also remarkably well tolerated and safe. As a result,
      conventional wisdom has been that MR contrast media are "biologically inert," a
      notion that is clearly false. Ultimately, it is the radiologist's responsibility
      to understand the potential adverse effects of Gd-based agents and the special
      situations in which they are likely to occur; however, the basic pharmacology of
      contrast agents is generally not included in medical school curricula or formally
      taught in residency. The purpose of this review is to discuss the mechanism of
      action of MR contrast agents and relevant aspects of their clinical pharmacology,
      including effects on the cardiovascular and renal systems, potential laboratory
      errors, and special situations involving women and children. We also briefly
      discuss the issue of nephrogenic systemic fibrosis (NSF).

PMID- 17457804
TI  - Segmentation of gadolinium-enhanced lesions on MRI in multiple sclerosis.
AB  - PURPOSE: To develop and implement a method for identification and quantification
      of gadolinium (Gd) enhancements with minimal human intervention. MATERIALS AND
      METHODS: Dual fast spin echo (FSE), fluid attenuation inversion recovery (FLAIR),
      and pre- and postcontrast T1-weighted spin echo were acquired on 22 subjects. The
      enhancements were identified on the postcontrast T1-weighted images based on
      morphological operations. A single threshold based on the ratio of the difference
      of postcontrast and precontrast T1 images with that of precontrast T1 images is
      applied to the reconstructed images to reduce the false classifications. False
      classification of enhancements arising from enhancing vasculature and structures
      such as the choroid plexus that lack a blood-brain barrier were reduced by
      assuming that the true enhancements are always associated with hyperintense
      lesions on T2-weighted images (T2 lesions). The enhanced lesions were further
      delineated based on fuzzy connectivity. RESULTS: The segmented Gd enhancements
      were evaluated quantitatively with manually identified enhancements based on
      similarity measures. The average similarity index (SI) of 0.76 suggests excellent
      performance of the proposed methodology. The Bland-Altman plot shows a close
      agreement between the results obtained manually and those based on the proposed
      methodology. CONCLUSION: The proposed algorithm identifies and quantifies Gd
      enhancements accurately with minimal human intervention.

PMID- 17457805
TI  - Autoalignment of intervertebral disks.
AB  - PURPOSE: To develop an automated planning method to obtain double oblique slices
      for clinically relevant diagnoses of spine-related pathologies. MATERIALS AND
      METHODS: Thirty healthy volunteers, 18 patients with cervical spine (c-spine)
      pathologies, and 15 patients with lumbar spine (l-spine) pathologies were
      included in this study. The planning method requires no interaction and is
      calculated online on the MR scanner after two sagittal acquisitions (a MR
      myelogram and standard T2-weighted (T2W) acquisition). The planning of the
      subsequent double oblique slice packets is calculated automatically. The results
      from the volunteers were evaluated visually by an operating technician. The
      results obtained in a clinical trial from interactive planning by an operating
      technician and from automated planning were compared. RESULTS: Visual assessment
      of the planned slices in the T2W images of all subjects confirmed the accuracy
      and robustness of the method for both applications. The differences in positions
      and orientations between interactively and automatically planned transverse
      series were within the range of interindividual variability. CONCLUSION: he new
      approach can be used to automatically plan double oblique MR images for
      examination of spine-related pathologies with high reliability and robustness.
      The major advantage is that simultaneous planning in the transversal-coronal and
      transversal-sagittal orientations can be performed without any additional
      measurement. Another advantage is that standardized localization of the nerve
      roots in the center of the image can be obtained.

PMID- 17457806
TI  - On the potential causal relationship between gadolinium-containing MRI agents and
      nephrogenic systemic fibrosis.

PMID- 17457807
TI  - Parallel imaging technique for the external carotid artery and its branches:
      comparison of balanced turbo field echo, phase contrast, and time-of-flight
      sequences.
AB  - PURPOSE: To evaluate the parallel imaging technique in the external carotid
      artery and its branches using 3D balanced turbo field echo (3D bTFE), 3D phase
      contrast (3D PC), and 3D time-of-flight (3D TOF) MR angiography (MRA) sequences.
      MATERIALS AND METHODS: A total of 26 healthy volunteer subjects underwent 3D
      bTFE, 3D PC, and 3D TOF MRA with the parallel imaging sensitivity encoding
      (SENSE) technique. The obtained images were read in a blinded fashion by three
      radiologists. Interreader and intersequence statistical analyses were performed
      to compare the visibility of the arteries. RESULTS: Friedman's ranking test
      demonstrated that there was no significant difference in visibility between any
      two pairs of sequences for the external carotid artery and its first branches.
      However, of the three techniques, 3D PC MRA performed the best for the second
      order branches (P < 0.01) and for overall visibility of the external carotid
      artery and its branches (P < 0.01). The 3D bTFE sequence is superior to 3D TOF;
      however, an effective means of separating arteries from veins and salivary ducts
      is needed. CONCLUSION: The combination of parallel imaging and the 3D PC
      technique is a promising approach for face and neck MRA.

PMID- 17457808
TI  - Safety update on the possible causal relationship between gadolinium-containing
      MRI agents and nephrogenic systemic fibrosis.

PMID- 17457809
TI  - Imaging strategies to reduce the risk of radiation in CT studies, including
      selective substitution with MRI.
AB  - "When one admits that nothing is certain one must, I think, also admit that some
      things are much more nearly certain than others." Bertrand Russell (1872-1970)
      Computed tomography (CT) is one of the largest contributors to man-made radiation
      doses in medical populations. CT currently accounts for over 60 million
      examinations in the United States, and its use continues to grow rapidly. The
      principal concern regarding radiation exposure is that the subject may develop
      malignancies. For this systematic review we searched journal publications in
      MEDLINE (1966-2006) using the terms "CT," "ionizing radiation," "cancer risks,"
      "MRI," and "patient safety." We also searched major reports issued from
      governmental U.S. and world health-related agencies. Many studies have shown that
      organ doses associated with routine diagnostic CT scans are similar to the low
      dose range of radiation received by atomic-bomb survivors. The FDA estimates that
      a CT examination with an effective dose of 10 mSv may be associated with an
      increased chance of developing fatal cancer for approximately one patient in
      2000, whereas the BEIR VII lifetime risk model predicts that with the same low
      dose radiation, approximately one individual in 1000 will develop cancer. There
      are uncertainties in the current radiation risk estimates, especially at the
      lower dose levels encountered in CT. To address what should be done to ensure
      patient safety, in this review we discuss the "as low as reasonably achievable"
      (ALARA) principle, and the use of MRI as an alternative to CT.

PMID- 17457810
TI  - MR colonography with fecal tagging: do individual patient characteristics
      influence image quality?
AB  - PURPOSE: To evaluate if different patient characteristics influence performance
      of fecal tagging (a new MR colonography (MRC) technique to label stool to avoid
      bowel cleansing) and, consecutively, MR image quality. MATERIALS AND METHODS: A
      total of 333 patients (mean age = 61 years) underwent MRC with fecal tagging.
      Four segments of the large bowel (ascending, transverse, descending, and sigmoid
      colon) were assessed as for the presence of nontagged stool particles, which can
      impede an assessment of the colonic wall. Ratings were correlated with patients'
      characteristics including patient age (<55 vs. > or =55 years), body mass index
      (BMI) (<25 vs. > or =25), gender, and acceptance levels for fecal tagging.
      Statistical analysis was performed using a Mann-Whitney U-test. RESULTS: A total
      of 1332 colonic segments were evaluated. Among them, 327 segments (25%) did not
      contain any visible stool particles. Considerably reduced image quality was found
      in 61 segments (5%). Best image quality was found in the sigmoid colon (mean
      value = 1.9), while image quality of the ascending colon turned out to be worst
      (mean value = 2.6). Fecal tagging effectiveness showed a reverse correlation with
      patient age. However, all other characteristics did not have a statistically
      significant influence on fecal tagging outcome. CONCLUSION: MRC in conjunction
      with barium-based fecal tagging led to diagnostic image quality in 95% of all
      colonic segments. Since tagging results were significantly decreased in patients
      > or =55 years, tagging protocols should to be modified in this group, i.e., by
      increasing the time interval of tagging administration.

PMID- 17457811
TI  - Time-courses of perfusion and phosphocreatine in rat leg during low-level
      exercise and recovery.
AB  - PURPOSE: To develop a noninvasive protocol for measuring local perfusion and
      metabolic demand in muscle tissue with sufficient sensitivity and time resolution
      to monitor kinetics at the onset of low-level exercise and during recovery.
      MATERIALS AND METHODS: Capillary-level perfusion, the critical factor that
      determines oxygen and substrate delivery to active muscle, was measured by an
      arterial spin labeling (ASL) technique optimized for skeletal muscle.
      Phosphocreatine (PCr) kinetics, which signal the flux of oxidative
      phosphorylation, were measured by (31)P MR spectroscopy. Perfusion and PCr
      measurements were made in parallel studies before, during, and after three
      different intensities of low-level, stimulated exercise in rat hind limb.
      RESULTS: The data reveal close coupling between the perfusion response and PCr
      changes. The onset and recovery time constants for PCr changes were independent
      of contractile force over the range of forces studied. Perfusion time constants
      during both onset of exercise and recovery tended to increase with contractile
      force. CONCLUSION: These results demonstrate that the protocol implemented can be
      useful for probing the mechanisms that control skeletal muscle blood flow, the
      physiological limits to muscle performance, and the causes for the attenuated
      exercise-induced hyperemia observed in disease states.

PMID- 17457812
TI  - STAT3: a critical transcription activator in angiogenesis.
AB  - Angiogenesis, the formation of new blood vessels from the pre-existing
      vasculature, is a complex multistage process regulated by a number of signal
      transduction pathways. Accumulating evidence suggests that signal transducer and
      activator of transcription (STATs), mainly STAT3, play an important role in
      angiogenesis under both physiological and pathological conditions in addition to
      cell survival, proliferation, differentiation, and oncogenesis. STAT3, as a
      critical multifunctional mediator, regulates many aspects of angiogenesis at the
      transcriptional level. This review will highlight the pivotal role of STAT3 in
      well-studied tumorous angiogenesis and cardiac angiogenesis, and summarize
      various potential mechanisms utilized by STAT3 to regulate the transcriptional
      activation of VEGF.

PMID- 17457813
TI  - In vivo screening identifies a highly folded beta-hairpin peptide with a
      structured extension.

PMID- 17457814
TI  - Molecular mechanisms of agr quorum sensing in virulent staphylococci.

PMID- 17457815
TI  - Measurement of homogeneous kinase activity for cell lysates based on the
      aggregation of gold nanoparticles.

PMID- 17457816
TI  - Controlled assembly of peptide nanotubes triggered by enzymatic activation of
      self-immolative dendrimers.

PMID- 17457817
TI  - Probing the role of the DXDD motif in Class II diterpene cyclases.

PMID- 17457818
TI  - Distributing a fixed amount of cyclic loading to tendon explants over longer
      periods induces greater cellular and mechanical responses.
AB  - Tendon overuse injuries are a major source of clinical concern. Cyclic loading
      causes material damage and induces biochemical responses in tendon. The purpose
      of this study was to examine the biochemical and biomechanical tendon response
      after applying cyclical loading over varying durations. Avian flexor digitorum
      profundus tendons were loaded (3 or 12 MPa) to a fixed number of cycles across
      either 1 or 12 days in vitro. The tendon response evaluations included
      biomechanical data gathered during loading and subsequent failure testing.
      Evaluations also included cellular viability, cell death, and proteoglycan,
      collagen, collagenase, and prostaglandin E(2) (PGE(2)) content measurements
      obtained from tissue specimens and media samples. Significant strains (up to 2%)
      accumulated during loading. Loading to 12 MPa significantly reduced maximum
      stress (33% and 27%) and energy density (42% and 50%) when applied across 1 or 12
      days, respectively. Loading to 3 MPa also caused a 40% reduction in energy
      density, but only when applied across 12 days. Cell death and collagenase
      activity increased significantly with increasing magnitude and duration. However,
      no differences occurred in cell viability or collagen content. Glycosaminoglycan
      content increased 50% with load magnitude, while PGE(2) production increased 2.5
      fold with loading magnitude and 11-fold with increased duration. Mechanical
      fatigue-induced mechanical property changes were exhibited by the tendons in
      response to increased loading magnitude across just 1 day. However, when the same
      loading was applied over a longer period, most outcomes were magnified
      substantially, relative to the short duration regimens. This is presumably due to
      the increased response time for the complex cellular response to loading. A key
      contributor may be the inflammatory mediator, PGE(2), which exhibited large
      magnitude and duration dependent increases to cyclic loading.

PMID- 17457819
TI  - Fabrication of a novel micron scale Y-structure-based chiral metamaterial:
      Simulation and experimental analysis of its chiral and negative index properties
      in the terahertz and microwave regimes.
AB  - In this report, we describe the fabrication of a chiral metamaterial based on a
      periodic array of Y-shaped Al structures on a dielectric Mylar substrate. The
      unit cell dimensions of the Y-structure are approximately 100 microm on a side
      with 8 microm linewidths. The fabricated Y-structure elements are characterized
      using scanning electron microscopy (SEM) and atomic force microscopy (AFM).
      Quantitative elemental analyses were carried out on both the Y-structure,
      comprised of Al and its oxide, as well as adjacent regions of the underlying
      mylar substrate using the energy dispersive X-ray spectroscopy (EDS) capability
      of the SEM. Finite-Difference Time-Domain (FDTD) calculations of the negative
      index of refraction for a 3D wedge of multiple layers of the 2D metamaterials
      showed that these metamaterials possess double negative (-mu,-epsilon)
      electromagnetic bulk properties at THz frequencies. The same negative index of
      refraction was determined for a wedge comprised of appropriately scaled larger Y
      structures simulated in the microwave region. This double negative property was
      confirmed experimentally by microwave measurements on a 3D wedge comprised of
      stacked and registered Y-structure sheets.

PMID- 17457820
TI  - Enabling nanomanufacturing using microscopy techniques.

PMID- 17457821
TI  - Three dimensional rendering of the mitochondrial sheath morphogenesis during
      mouse spermiogenesis.
AB  - In the middle piece of mouse sperm tail, the idea of the mitochondria wrapping in
      a sinistral (left-handed) double helical structure was generally accepted. In the
      existing model, mitochondria aligned in four longitudinal rows (stage 1) and
      twisted dextrally (right-handed) (stage 2) and began to stagger, where opposing
      rows of mitochondria contacted each other to form a sinistral double helix (stage
      3), finally, the end-on touching mitochondria further elongated to their mature
      length (stage 4). However, in this model, mitochondria need to shift a long
      distance and reposition themselves. Since no gaps have been found in
      mitochondrial sheath, repositioning of most mitochondria along the middle piece
      is unlikely to happen. Therefore, we reapproached the questions through three
      dimensional rendering to provide a new model for mitochondrial sheath formation.
      In our proposed model, four dextrally arranged spherical mitochondrial arrays
      were considered stage 1 (resembles stage 2 of the old model). In stage 2
      (resembles stage 3 of the old model), a critical difference was found that pairs
      of mitochondria from the opposing arrays formed ring-like structures instead of a
      sinistral double helix. In stage 3, which was not observed in the old model,
      mitochondria staggered in a specific pattern to form the sinistral double helix.
      In stage 4, mitochondria elongated from crescent-shaped to rod-shaped structures.
      The new model proposed here would allow each mitochondrion to stay at where they
      attached first and elongate laterally from two directions to reach their final
      double helical structure without unreasonable great distance shift along the
      outer dense fibers.

PMID- 17457822
TI  - Hematoma resolution as a target for intracerebral hemorrhage treatment: role for
      peroxisome proliferator-activated receptor gamma in microglia/macrophages.
AB  - OBJECTIVE: Phagocytosis is necessary to eliminate the hematoma after
      intracerebral hemorrhage (ICH); however, release of proinflammatory mediators and
      free radicals during phagocyte activation is toxic to neighboring cells, leading
      to secondary brain injury. Promotion of phagocytosis in a timely and efficient
      manner may limit the toxic effects of persistent blood products on surrounding
      tissue and may be important for recovery after ICH. METHODS: Intrastriatal blood
      injection in rodents and primary microglia in culture exposed to red blood cells
      were used to model ICH and to study mechanisms of hematoma resolution and
      phagocytosis regulation by peroxisome proliferator-activated receptor gamma
      (PPARgamma) in microglia/macrophages. RESULTS: Our study demonstrated that the
      PPARgamma agonist, rosiglitazone, promoted hematoma resolution, decreased
      neuronal damage, and improved functional recovery in a mouse ICH model. Microglia
      isolated from murine brains showed more efficient phagocytosis in response to
      PPARgamma activators. PPARgamma activators significantly increased PPARgamma
      regulated gene (catalase and CD36) expression, whereas reducing proinflammatory
      gene (tumor necrosis factor-alpha, interleukin-1beta, matrix metalloproteinase-9,
      and inducible nitric oxide synthase) expression, extracellular H(2)O(2) level,
      and neuronal damage. Phagocytosis by microglia was significantly inhibited by
      PPARgamma gene knockdown or neutralizing anti-CD36 antibody, whereas it was
      enhanced by exogenous catalase. INTERPRETATION: PPARgamma in macrophages acts as
      an important factor in promoting hematoma absorption and protecting other brain
      cells from ICH-induced damage.

PMID- 17457823
TI  - Effect of robotic milling on periprosthetic bone remodeling.
AB  - The ROBODOC system has provided better fit and fill of the stem and less
      destruction of the bony architecture than with manual surgery. These benefits
      might affect femoral periprosthetic bone remodeling. We evaluated the effects of
      robotic milling in cementless total hip arthroplasty (THA) in a longitudinal 24
      month follow-up study using dual energy X-ray absorptiometry (DEXA) and plain
      radiographs of 29 patients (31 hips) after ROBODOC THA and 24 patients (27 hips)
      after manual THA with the same stem design. To minimize the influence of other
      factors on bone remodeling, only female osteoarthritis patients, who had no drugs
      that might affect bone metabolism were enrolled. Significantly less bone loss
      occurred at the proximal periprosthetic areas in the ROBODOC group. In zone 1,
      the decrease was 15.5 versus 29.9% using conventional rasping; in zone 7, the
      loss was 17.0% with ROBODOC compared to 30.5% with conventional rasping (p <
      0.05). On radiographs, endosteal spot welds in the proximal medial portion were
      more pronounced in the ROBODOC group (48 vs. 11% in the conventional group, p <
      0.05). Our results suggest that robotic milling is effective in facilitating
      proximal load transfer around the femoral component and minimizing bone loss
      after cementless THA.

PMID- 17457824
TI  - Mechanics of oriented electrospun nanofibrous scaffolds for annulus fibrosus
      tissue engineering.
AB  - Engineering a functional replacement for the annulus fibrosus (AF) of the
      intervertebral disc is contingent upon recapitulation of AF structure,
      composition, and mechanical properties. In this study, we propose a new paradigm
      for AF tissue engineering that focuses on the reconstitution of anatomic fiber
      architecture and uses constitutive modeling to evaluate construct function. A
      modified electrospinning technique was utilized to generate aligned nanofibrous
      polymer scaffolds for engineering the basic functional unit of the AF, a single
      lamella. Scaffolds were tested in uniaxial tension at multiple fiber
      orientations, demonstrating a nonlinear dependence of modulus on fiber angle that
      mimicked the nonlinearity and anisotropy of native AF. A homogenization model
      previously applied to native AF successfully described scaffold mechanical
      response, and parametric studies demonstrated that nonfibrillar matrix, along
      with fiber connectivity, are key contributors to tensile mechanics for engineered
      AF. We demonstrated that AF cells orient themselves along the aligned scaffolds
      and deposit matrix that contributes to construct mechanics under loading
      conditions relevant to the in vivo environment. The homogenization model was
      applied to cell-seeded constructs and provided quantitative measures for the
      evolution of matrix and interfibrillar interactions. Finally, the model
      demonstrated that at fiber angles of the AF (28 degrees -44 degrees ), engineered
      material behaved much like native tissue, suggesting that engineered constructs
      replicate the physiologic behavior of the single AF lamella. Constitutive
      modeling provides a powerful tool for analysis of engineered AF neo-tissue and
      native AF tissue alike, highlighting key mechanical design criteria for
      functional AF tissue engineering.

PMID- 17457825
TI  - High fever-related maternal diseases as possible causes of multiple congenital
      abnormalities: a population-based case-control study.
AB  - BACKGROUND: Multiple congenital abnormalities (MCAs) represent the most severe
      category of structural birth defects; therefore, we decided to evaluate the
      possible etiological factors for MCAs. METHODS: The population-based large data
      set of the Hungarian Case-Control Surveillance of Congenital Abnormalities (1980
      1996) was evaluated. RESULTS: We compared the data of 1,349 cases with MCAs,
      2,405 matched population controls without any defect, and 21,494 malformed
      controls with isolated congenital abnormalities. An association was found between
      a higher risk for MCAs and high fever-related influenza, common cold with
      secondary complications, tonsillitis, and recurrent orofacial herpes (adjusted
      ORs with 95% CIs: 2.3, 1.8-2.9). However, the risk for MCAs was reduced by
      antifever drug therapy (adjusted OR with 95% CI: 1.6, 0.9-2.9). CONCLUSIONS: An
      association was found between high fever-related maternal diseases and a higher
      risk for MCAs; however, a certain portion of these MCAs is preventable by
      antifever therapy.

PMID- 17457827
TI  - Cost-effectiveness of influenza vaccination in working-age cancer patients.
AB  - BACKGROUND: Despite recommendations to immunize all patients at an increased risk
      of influenza complications, the vaccine utilization among high-risk nonelderly
      adults remains low and its cost-effectiveness is unclear. In the current study,
      the authors analyzed the cost-effectiveness of influenza vaccination in working
      age (ages 20-64 years) cancer patients. METHODS: The authors developed a decision
      analytic model, from the societal perspective, using epidemiologic, vaccine
      effectiveness, resource utilization, cost, survival, and utility data from
      published sources, supplemented with data collected from the authors' own
      institutional accounting system. Two strategies were compared: influenza
      vaccination of working-age cancer patients and no vaccination. The base-case
      patient was assumed to be a 51-year-old cancer patient (the mean age for the
      National Cancer Institute's Surveillance, Epidemiology, and End Results [SEER]
      population of working-age patients within 5 years of cancer diagnosis). RESULTS:
      The effectiveness of the influenza vaccine was 6.02 quality-adjusted life-years
      (QALYs) at a cost of $30.10. The effectiveness of the no vaccination strategy was
      6.01 QALYs at a cost of $27.86. Compared with the no vaccination strategy, the
      incremental cost-effectiveness ratio of vaccinating working-age cancer patients
      would be $224.00 per QALY gained. Using the benchmark of $50,000 per QALY, the
      model was only sensitive to changes in cancer survival (threshold of 2.8 months).
      CONCLUSIONS: The influenza vaccine is cost-effective for working-age cancer
      patients with a life expectancy of >or=3 months. All working-age cancer patients
      who are within 5 years of cancer diagnosis and have a life expectancy of at least
      3 months should be vaccinated against influenza.

PMID- 17457828
TI  - Measurement of varus-valgus and internal-external rotational knee laxities in
      vivo--Part I: assessment of measurement reliability and bilateral asymmetry.
AB  - We examined the capabilities of the Vermont Knee Laxity Device (VKLD) in
      measuring varus (VR)-valgus (VL) and internal (INT)-external (EXT) rotational
      laxities by quantifying measurement consistency and absolute measurement error (N
      = 10). Based on the expected measurement error, we then examined side-to-side
      differences (N = 20). For all measures, the knee was flexed 20 degrees , the
      thigh securely fixed, and counterweights applied to the thigh and shank to create
      an initial zero shear and compressive load across the tibiofemoral joint. A 10-Nm
      torque was applied to the knee for VL and VR during non-weight-bearing, and a 5
      Nm torque was applied for INT and EXT during non-weight-bearing and weight
      bearing conditions. Position sensors measured angular displacements (deg). Except
      for INT during weight bearing, measurement consistency was good to excellent
      (range, 0.68-0.96), with absolute measurement errors generally less than 2
      degrees for VR-VL and 3-4 degrees for INT-EXT. Although side-to-side differences
      were observed, they did not exceed absolute measurement errors. The VKLD yields
      reliable measures of VR-VL and INT-EXT laxities, with sufficient measurement
      precision to yield clinically relevant differences.

PMID- 17457829
TI  - In vivo effects of coating loaded and unloaded Ti implants with collagen,
      chondroitin sulfate, and hydroxyapatite in the sheep tibia.
AB  - The in vivo effects of coating titanium implants with organic extracellular
      matrix molecules were examined in the sheep tibia. Titanium screws (5.0 mm) were
      coated with type I collagen (Ti/Coll) or type I collagen and chondroitin sulfate
      (Ti/Coll/CS) by biomimetic fibrillogenesis. Uncoated screws (Ti) and screws
      coated with hydroxyapatite (Ti/HA) served as control. Six adult female sheep
      received one screw of each type to stabilize a midshaft tibial fracture with
      external fixation. Four cylindrical implants of 4-mm outer diameter and 3.3-mm
      inner diameter with the same coatings were inserted into the tibial head. No pin
      track infections were seen at the time of implant retrieval 6 weeks after
      implantation. Extraction torque was greater for Ti/HA (1181 Nmm) and Ti/Coll/CS
      (1088 Nmm) compared to Ti/Coll (900 Nmm) and Ti (904 Nmm) [N.S.]. Newly formed
      bone was noted around all coated screws within the medullary cavity. Macrophage
      and osteoclast activity was significantly reduced around Ti/Coll/CS in both types
      of implants compared to uncoated controls (p < 0.05). Osteoblast activity was
      significantly increased around loaded Ti/Coll and Ti/Coll/CS screws compared to
      uncoated Ti screws (p < 0.05). Microtomographic evaluation (SRmicroCT) revealed
      no significant differences in new bone formation around the unloaded tibial head
      implants. Coating of external fixation devices with of type I collagen and
      chondroitin sulfate appears to have similar effects with respect to stability and
      bone healing as HA but with less osteoclast activity. These findings were more
      pronounced under loaded than unloaded conditions in the sheeptibia.

PMID- 17457830
TI  - Barriers to rehabilitation following surgery for primary breast cancer.
AB  - Surgery is a mainstay of primary breast cancer therapy. Alterations in surgical
      technique have reduced normal tissue injury, yet pain and functional compromise
      continue to occur following treatment. A tenuous evidence base bolstered by
      considerable expert opinion suggests that early intervention with conventional
      rehabilitative modalities can reduce surgery-associated pain and dysfunction.
      Barriers to the timely rehabilitation of functionally morbid sequelae are
      discussed at length in this article. Barriers arise from a wide range of
      academic, human, logistic, and financial sources. Despite obstacles, expeditious
      and effective post-surgical rehabilitation is being regularly delivered to breast
      cancer patients at many institutions. This experience has given rise to anecdotal
      information on the management of common sequelae that may undermine function. The
      epidemiology, pathophysiology, and management of these sequelae are outlined in
      this article with an emphasis on the caliber of supporting evidence. Myofascial
      dysfunction, axillary web syndrome, frozen shoulder, lymphostasis, post
      mastectomy syndrome, and donor site morbidity following breast reconstruction are
      addressed. A critical need for more definitive evidence to guide patient
      management characterizes the current treatment algorithms for surgical sequelae.

PMID- 17457831
TI  - Determination of bevantolol enantiomers in human plasma by coupled achiral-chiral
      high performance-liquid chromatography.
AB  - A coupled achiral-chiral high performance liquid chromatographic method was
      developed and fully validated for the determination of bevantolol enantiomers, (
      )-(S)-bevantolol and (+)-(R)-bevantolol, in human plasma. Plasma samples were
      prepared by solid phase extraction with Sep-Pak Plus C18 cartridges followed by
      HPLC. Bevantolol enantiomers and (+)-(R)-Propranolol as internal standard (IS)
      were preseparated from interfering components in plasma on a Phenomenex silica
      column and bevantolol enantiomers and IS were resolved and determined on a
      Chiralcel OJ-H chiral stationary phase. The two columns were connected by a
      switching valve equipped with silica precolumn. The Precolumn was used to
      concentrate bevantolol in the eluent from the achiral column before back flushing
      onto chiral phase. A detailed validation of the method was performed accordingly
      to FDA guidelines. For each enantiomer the assay was linear between 20 and 1600
      ng/ml. The quantification limits of both bevantolol enantiomers were 20 ng/ml.
      The intraday variation was between 1.07 and 12.64% in relation to the measured
      concentration and the interday variation was 0.91 and 11.79%. The method has been
      applied to the determination of (-)-(S)- and (+)-(R)-bevantolol in plasma from
      healthy volunteers dosed with racemic bevantolol hydrochloride.

PMID- 17457832
TI  - Metal-induced supramolecular chirality in optically active polymers of oxazoline
      substituted N-phenylmaleimides.
AB  - Polymerization of N-phenylmaleimide derivatives bearing a chiral oxazoline
      substituent at ortho-position on the phenyl group (namely, N-[o-(4,5-dihydro-1,3
      oxazol-2-yl)phenyl]maleimides, OPMI) was carried out with diethylzinc (Et2Zn) as
      an initiator. The resulting polymers exhibited a quite high specific rotation and
      a unique split-type circular dichroism. Furthermore, an induced Cotton effect was
      observed in the pi-pi* transition region of the chromophores upon complexation of
      these polymers with copper(II) salt in tetrahydrofuran solution, indicating the
      formation of chiral supramolecular aggregates. The induced supramolecular
      chirality was found to be dependent on the absolute configuration of monomer
      units, that is, the polymers with (R)-configurational oxazolinyl chromophores
      tended to form chiral aggregates with levorotatory handedness, while polymers
      obtained from the (S)-monomer offered dextrogyrate one upon the addition of
      Cu(II) salt.

PMID- 17457833
TI  - Application of liquid chromatography-tandem mass spectrometry method for the
      analysis of new nonselective beta-adrenergic blocker 1-(1-H-indol-4-yloxy)-3-{[2
      (2-methoxy phenoxy)ethylo]amino}propan-2-ol (2F109) in rat plasma.
AB  - A sensitive and specific liquid chromatography electrospray ionization-tandem
      mass spectrometry method for the enantioselective determination of the novel beta
      adrenolytic compound, 1-(1-H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethylo]amino}
      propan-2-ol, in rat plasma has been developed and validated. Chromatography was
      performed on a reversed-phase Chiralcel OD-RH analytical column (150x4.6 mm, 5
      microm, Daicel Chemical Industries, Tokyo, Japan) with isocratic elution using a
      mobile phase containing acetonitrile and water with 0.01% formic acid. Detection
      was achieved by an Applied Biosystems MDS Sciex (Concord, Ontario, Canada) API
      2000 triple quadrupole mass spectrometer. Electrospray ionization (ESI) was used
      for ion production. The limit of detection in the MRM mode was found to be 1.25
      ng/ml. The limit of quantification of both enantiomers was 2.5 ng/ml. The
      precision and accuracy for both intra- and inter-day determination of 2F109
      enantiomers ranged from 2.6 to 12% and from 89.1 to 107.1%. This analytical
      method allowed us to carry out pharmacokinetic studies in rats. Our findings
      demonstrate that 2F109 shows stereoselective disposition in rat plasma after i.v.
      administration. The terminal half-lives of (+)-(R)-2F109 and (-)-(S)-2F109 were
      33.5 and 42.6 min, respectively. The AUC0-inf of (+)-(R)-2F109 exceeded that of (
      )-(S)-2F109.

PMID- 17457834
TI  - 5-ALA for photodynamic photorejuvenation--optimization of treatment regime based
      on normal-skin fluorescence measurements.
AB  - BACKGROUND AND OBJECTIVES: Photodynamic therapy using 20% 5 aminolevulinic acid
      (5-ALA) has recently been introduced as a new tool in optical skin rejuvenation.
      The primary objective of this study was to optimize incubation time, the topical
      delivery mechanism (vehicle) and the concentration of 5-ALA by detecting the
      dynamic changes of normal skin after 5-ALA application. The secondary objective
      was to develop a treatment regime which minimizes post-treatment
      photosensitivity. STUDY DESIGN/MATERIALS AND METHODS: Skin fluorescence
      distribution patterns after topical application of low concentrations of 5-ALA
      (0.5% and 1% preparations encapsulated in liposomes), were investigated. Twenty
      percent 5-ALA in moisturizing cream was used as a control. Ten healthy volunteers
      participated, and skin fluorescence was documented by fluorescent photography.
      The fluorescent intensity was measured in % of maximum obtained fluorescence
      after 3 hours 5-ALA application. RESULTS: Skin fluorescence intensity after
      topical application of 0.5% and 1% non-occluded liposome-encapsulated 5-ALA
      application was heterogeneous distributed and reached saturation level after
      approximate 2 hours. The maximal fluorescence for 0.5% and 1% 5-ALA treated areas
      was 4.2% (SD: 3.5%) and 2.4% (SD: 2%), respectively, and this difference was
      statistically significant (P = 0.036). The fluorescence decayed linearly shortly
      (within 15 minutes) after end of application and was back to baseline within 8
      hours. In contrast, the fluorescence of areas treated more than 1 hour with 20% 5
      ALA was very uniform and a linear relationship (r2 = 0.998) to the incubation
      time (0-3 hours) was registered. Furthermore, fluorescence intensity (15.2-57.9%)
      continued to increase after the end of 5-ALA application. The maximum
      fluorescence reach a level of 1.6-9 times the fluorescence measured by end of the
      5-ALA application and occurred 8:13 hours (SD: 0:49 hours) after the end of 20% 5
      ALA application. The average skin surface fluorescence induced by the liposome
      encapsulated 0.5% 5-ALA applied for longer than 2 hours, was found to be
      statistically equal (P = 0.47) to the average measured skin surface fluorescence
      (4.2%) obtained after 30 minutes exposure to 20% 5-ALA cream (4.3%). CONCLUSION:
      Changing the 5-ALA vehicle from a moisturizing cream to liposome encapsulation,
      the 5-ALA concentration can be lowered by a factor of 40, and still induce the
      same skin fluorescence and at the same time eliminates the need for occlusion.
      The low post-treatment fluorescence also suggests a significantly reduced risk of
      post-treatment phototoxicity.

PMID- 17457835
TI  - Prospective direct comparison study of fractional resurfacing using different
      fluences and densities for skin rejuvenation in Asians.
AB  - BACKGROUND AND OBJECTIVE: Fractional resurfacing is a new concept of cutaneous
      remodeling whereby laser-induced zones of microthermal injury are surrounded by
      normal untreated tissue. The aim of this study is to compare the efficacy and
      complications of Fraxel laser treatment when using different fluences and density
      settings. STUDY DESIGN/MATERIALS AND METHODS: Thirty female Asian patients were
      enrolled in the study. Group 1 (n = 10); half of the face was treated with eight
      passes at 125 MTZ/cm2 at an energy setting of 8 mJ. The other half of the face
      was treated with eight passes at 250 MTZ/cm2 at an energy setting of 8 mJ. Group
      2 (n = 10); half of the face was treated with eight passes at 125 MTZ/cm2 at an
      energy setting of 8 mJ. The other half of the face was treated with eight passes
      at 125 MTZ/cm2 at an energy setting of 16 mJ. Group 3 (n = 10); half of the face
      was treated with eight passes at 125 MTZ/cm2 at an energy setting of 16 mJ. The
      other half of the face was treated with eight passes at 250 MTZ/cm2 at an energy
      setting of 8 mJ. Ice pack cooling was used during and after laser treatment. The
      patients were evaluated for clinical efficacy and treatment-related side effects.
      RESULTS: Pain, erythema, and swelling were observed to be significantly more
      evident or persisted longer in patients treated with higher densities and
      fluences (P<0.01). Patient satisfaction is significantly greater in patients
      treated with higher fluences (P<0.05), but not in patients treated with higher
      densities. Hyperpigmentation was observed in two patients. CONCLUSION: Increased
      density was more likely to produce swelling, redness, and hyperpigmentation when
      compared to increased energy. Patient satisfaction is significantly higher when
      their skin is treated with high fluences, but not when patients' skin is treated
      with high densities.

PMID- 17457836
TI  - A comparison of mass removal, thermal injury, and crater morphology of cortical
      bone ablation using wavelengths 2.79, 2.9, 6.1, and 6.45 microm.
AB  - BACKGROUND AND OBJECTIVE: Previous investigations have reported evidence of
      wavelength dependence on cortical bone ablation. This study used mid-infrared
      laser wavelengths generated by a free electron laser (FEL) and mass removal
      measurements to further examine the ablation efficiency of a wavelength (2.79
      microm) not previously reported and three wavelengths (2.9, 6.1, and 6.45 microm)
      previously demonstrated by crater morphology alone to be efficient for cortical
      bone removal. STUDY DESIGN/MATERIALS AND METHODS: The wavelengths examined were
      provided by an FEL emitting 4 microseconds macropulses consisting of 1-2
      picoseconds duration micropulses delivered at 350 picoseconds intervals. The mass
      removal measurements were conducted by a microbalance, and the collateral thermal
      injury and crater morphology of cortical bone were examined by light microscopy
      following standard histologic processing. RESULTS: The study demonstrated that
      the highest mass removal was achieved at lambda = 6.1 microm followed by, in
      order, lambda = 2.9, 6.45, and 2.79 microm. The zones of thermal injury and
      crater morphology created in cortical bone at the selected wavelengths were
      examined at the radiant exposure of 28.3 J/cm2. Ablation using lambda = 6.1
      microm provided the largest crater size and the least collateral thermal injury.
      The greatest amount of collateral thermal injury was produced by lambda = 2.79
      microm at both the sides and base of the ablation crater. CONCLUSIONS: The mass
      removal of cortical bone produced by FEL ablation at selected mid-IR wavelengths
      was measured as a function of incident radiant exposure. The ablation efficiency
      was found to be dependent upon wavelength. The lambda = 2.79 microm did not offer
      any improvement over the other wavelengths evaluated, suggesting that a potential
      shift in the dynamic optical properties of water during tissue irradiance with
      the FEL does not present an advantage to the cutting of cortical bone. The lambda
      = 6.1 microm provided the highest ablation efficiency with deepest crater and the
      least amount of collateral thermal injury.

PMID- 17457837
TI  - Flexible UV light guiding system for intraocular laser microsurgery.
AB  - BACKGROUND AND OBJECTIVE: Until now, UV lasers could not be applied to
      vitreoretinal surgery because of the absence of a practical beam guiding system.
      A flexible, freely mobile hollow core waveguide, capable of delivering UV laser
      light, was recently developed. We evaluated the feasibility of this UV laser
      guiding system for vitreoretinal surgery in enucleated porcine and rabbit eyes
      and in vivo on rabbit retina. MATERIALS AND METHODS: 193-nm argon fluoride (ArF)
      excimer laser and a 5th harmonic Nd:YAG laser with the wavelength of 213 nm were
      used as a light source. A hollow core waveguide was connected to a handpiece with
      a 20-gauge endoprobe as an instrument for vitreoretinal surgery. RESULTS: Cutting
      of the retina was possible only with contact technique. With a selected
      repetition rate of 20 Hz, sharp, full-depth dissection of porcine retinas was
      achieved only with 1.0 J/cm2. With the repetition rate of 50 Hz, even 0.05 J/cm2
      could incise the total thickness of rabbit retina with no histological damage of
      the underlying retinal pigment epithelium. The ease in using the instrument for
      vitreoretinal surgery was confirmed by the in vivo experiment. CONCLUSION: This
      study revealed the potential use of the new type of the UV laser scalpel,
      connected to a hollow core waveguide, to perform precise, "cold," and
      tractionless cutting during vitreoretinal surgery.

PMID- 17457839
TI  - Hair stimulation following laser and intense pulsed light photo-epilation: review
      of 543 cases and ways to manage it.

PMID- 17457840
TI  - Body contouring by non-invasive transdermal focused ultrasound.
AB  - BACKGROUND AND OBJECTIVES: The risks of currently available invasive procedures
      in body contouring motivate a need for safer, non-invasive technologies for
      improving the appearance of body silhouette. A new device has been developed that
      uses focused therapeutic ultrasound to reduce adipose tissue non-invasively. The
      aim of this study was to assess the efficacy and safety of a novel non-invasive
      focused ultrasound system (UltraShape Ltd, Tel Aviv, Israel) in reducing
      localized fat deposits to improve body contours. STUDY DESIGN/PATIENTS AND
      METHODS: A prospective study was conducted on 30 healthy patients. All patients
      underwent three treatments, at 1-month intervals, and were followed for 1 month
      after the last treatment. Areas treated were the abdomen, inner and outer thighs,
      flanks, inner knees, and breasts (males only). No other body contouring procedure
      was used during the study. Efficacy was determined by change in fat thickness,
      assessed by ultrasound measurements, and by circumference measurements. Weight
      change was monitored to assess whether reduction in fat thickness or
      circumference was dependent on or independent of weight loss. Safety was
      determined by clinical findings, assays of serum triglycerides, and liver
      ultrasound evaluation for the presence of steatosis. RESULTS: All patients showed
      significant reduction in subcutaneous fat thickness within the treated area. The
      mean reduction in fat thickness after three treatments was 2.28+/-0.80 cm.
      Circumference was reduced by a mean of 3.95+/-1.99 cm. Weight was unchanged
      during the treatment and follow-up period. No adverse effects were observed.
      CONCLUSIONS: This study shows the efficacy and safety of focused ultrasound,
      using the UltraShape Contour I, as a non-invasive transdermal method for reducing
      unwanted fat deposits in the body. Multiple treatments combined with appropriate
      patient and treatment area selection can produce dramatic improvements in body
      contour.

PMID- 17457841
TI  - Photothermolysis of blood vessels using indocyanine green and pulsed diode laser
      irradiation in the dorsal skinfold chamber model.
AB  - BACKGROUND AND OBJECTIVE: For the treatment of vascular lesions, the use of laser
      light absorbed by the endogenous chromophore hemoglobin may still be improved.
      MATERIALS AND METHODS: Laser treatment (lambda(em) = 805 nm; fluence rate: 106
      kW/cm2; fluence: 3.2 J/cm2 (3 milliseconds)), of blood vessels directly after
      i.v. application of indocyanine green (ICG) (ICG-concentration: 0, 2, or 4 mg/kg
      body weight (b.w.)) (n = 14,117) was investigated in the skinfold chamber model.
      Vessel diameters (1-351 microm) were measured using intravital fluorescence
      microscopy up to 24 hours following irradiation. Histology was taken 1 or 24
      hours after irradiation. Results were compared to a mathematical model based on
      the finite element method. RESULTS: The reduction of blood vessel perfusion was
      proportional to ICG-concentration and pulse duration; only a 30 milliseconds
      pulse duration (2 or 4 mg/kg b.w. ICG-concentration) induced a loss of perfusion
      even of blood vessels with a diameter <30 microm. Histology revealed
      photocoagulation of blood vessels up to 24 hours. Results were in agreement with
      mathematical calculations. CONCLUSION: ICG-mediated laser irradiation induces
      irreversible photocoagulation of blood vessels of all diameters in this model.

PMID- 17457842
TI  - Flashlamp pulsed-dye laser suppressed TGF-beta1 expression and proliferation in
      cultured keloid fibroblasts is mediated by MAPK pathway.
AB  - BACKGROUND AND OBJECTIVES: Our previous clinical study indicated that
      transforming growth factor-beta1 (TGF-beta1) and mitogen-activated protein
      kinases (MAPK) are both involved in keloid regression following flashlamp pulsed
      dye laser (PDL). To further characterize of this involvement, this work examined
      whether PDL suppression of TGF-beta1 expression was mediated through MAPK pathway
      in cultured keloid fibroblasts (KF). STUDY DESIGN/MATERIALS AND METHODS: Primary
      culture of KF harvested from keloid patients received various dosages of PDL
      treatment in 585-nm wavelength. TGF-beta1 expressions in KF following various
      dosages of PDL were assessed. Additionally, MAPK pathway activities were studied
      using the PD98059 (an ERK inhibitor), SB203580 (a p38 kinase inhibitor), and
      SP600125 (a JNK inhibitor), to determine the role in keloid following PDL
      treatment. Activator protein-1 (AP-1), a transcription factor of TGF-beta, was
      analyzed by electrophoretic mobility shift assay (EMSA). Phosphorylated c-Jun,
      one of the components of AP-1, was also detected. RESULTS: The observation
      results demonstrated that optimal dosages of PDL significantly suppressed KF
      proliferation and TGF-beta1 expression. EMSA study identified PDL downregulation
      of super-shift of AP-1. Three subtypes of MAPK cascades were augmented between 30
      minutes and 4 hours following PDL treatment, particularly phosphorylation of
      ERK1/2 and p38. Pre-treatment with PD98059, SB203580, but not SP600125, markedly
      inhibited the downregulating effects of TGF-beta1 and phosphorylated c-Jun
      expression following PDL treatment. CONCLUSION: PDL induced keloid regression is
      mediated by triggering MAPK cascades and blockade of AP-1 transcription and TGF
      beta expression. Modulation of TGF-beta and MAPK interaction in keloids may
      provide specific targets for therapeutic intervention.

PMID- 17457843
TI  - Cultured epithelial cells response to phototherapy with low intensity laser.
AB  - BACKGROUND AND OBJECTIVES: Little is known about the intracellular response of
      epithelial cells to phototherapy. The aim of this in vitro study was to analyze
      the effect of phototherapy with low-energy lasers with different wavelengths and
      powers on cultured epithelial cell growth under different nutritional conditions.
      STUDY DESIGN/MATERIALS AND METHODS: Epithelial cell cultures (Vero cell line)
      grown in nutritional deficit in culture medium supplemented with 2% fetal bovine
      serum (FBS) were irradiated with low-energy laser from one to three times with a
      GaAlAs laser (660 nm) and InGaAlP (780 nm), 40 and 70 mW, respectively, with 3 or
      5 J/cm2. Cell growth was indirectly assessed by measuring the cell mitochondrial
      activity. RESULTS: Nonirradiated cell cultures grown in nutritional regular
      medium supplemented with 10% FBS produced higher cell growth than all cultures
      grown in nutritional deficit irradiated or not. The overall cell growth of
      cultures grown under nutritionally deficit conditions was significantly improved
      especially when irradiated with 780 nm for three times. CONCLUSIONS: Phototherapy
      with the laser parameters tested increases epithelial cell growth rate for cells
      stressed by growth under nutritionally deficient states. This cell growth
      improvement is directly proportional to the number of irradiations; however, was
      not enough to reach the full cell growth potential rate of Vero epithelial cell
      line observed when growing under nutritional regular condition.

PMID- 17457844
TI  - Low-level laser irradiation (LLLI) promotes proliferation of mesenchymal and
      cardiac stem cells in culture.
AB  - BACKGROUND AND OBJECTIVES: Low-level laser irradiation (LLLI) was found to
      promote the proliferation of various types of cells in vitro. Stem cells in
      general are of significance for implantation in regenerative medicine. The aim of
      the present study was to investigate the effect of LLLI on the proliferation of
      mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs). STUDY
      DESIGN/MATERIALS AND METHODS: Isolation of MSCs and CSCs was performed. The cells
      were cultured and laser irradiation was applied at energy densities of 1 and 3
      J/cm2. RESULTS: The number of MSCs and CSCs up to 2 and 4 weeks respectively,
      post-LLLI demonstrated a significant increase in the laser-treated cultures as
      compared to the control. CONCLUSION: The present study clearly demonstrates the
      ability of LLLI to promote proliferation of MSCs and CSCs in vitro. These results
      may have an important impact on regenerative medicine.

PMID- 17457845
TI  - Health disparities and culturally specific treatment: perspectives and
      expectancies of African American smokers.
AB  - Researchers suggest that culturally specific (CS) interventions are important in
      addressing smoking-related health disparities. Yet, little research has examined
      the perspectives of African American smokers regarding these efforts. This
      qualitative study sought to gain insight into perceptions related to (a) the
      smoking prevalence among African Americans, (b) smoking-related health
      disparities, (c) expectancies for CS interventions, (d) methods of recruiting
      research participants, and (e) key intervention components. Six focus groups were
      conducted with 41 African American smokers (aged 21-64) at a community health
      center. Content analyses revealed several themes, including the perception that
      smoking is normative among African Americans, limited knowledge of racial health
      disparities, mixed perceptions regarding race as a risk factor for illness, and
      mixed expectancies for the efficacy of CS interventions. In conclusion,
      individual differences, such as smoking norms, knowledge of health disparities,
      and intervention expectations may influence receptivity to CS treatments.
      Implications for tobacco interventions among African Americans are discussed.

PMID- 17457846
TI  - The voices acceptance and action scale (VAAS): Pilot data.
AB  - Acceptance and mindfulness methods that emphasise the acceptance rather than
      control of symptoms are becoming more central to behavioural and cognitive
      therapies. Acceptance and Commitment Therapy (ACT) is the most developed of these
      methods; recent applications of ACT to psychosis suggest it to be a promising
      therapeutic approach. However, investigation of the mechanisms of therapy within
      this domain is difficult because there are no acceptance-based measures available
      specifically for psychotic symptoms. This paper describes the preliminary
      evaluation of a self-report instrument designed to assess acceptance-based
      attitudes and actions in relation to auditory and command hallucinations.
      Following initial scale development, a 56-item version of the Voices Acceptance
      and Action Scale (VAAS) was administered to 43 participants with command
      hallucinations as part of their baseline assessment in a larger trial. Measures
      of symptoms, quality of life, and depression were also administered. The scale
      was examined for reliability using corrected item total statistics. Based on this
      method, 31 items were retained. Internal consistency and test-retest reliability
      for the 31-item VAAS were acceptable. Subsequent examination of construct
      validity showed the VAAS to correlate significantly in the expected directions
      with depression, quality of life, and coping with command hallucinations. It also
      discriminated compliance from non-compliance with harmful command hallucinations.
      Although these results are preliminary and subject to a number of limitations,
      the VAAS shows promise as a useful aid in the assessment of the psychological
      impact of voices.

PMID- 17457847
TI  - The relationships of antisocial behavior with attachment styles, autonomy
      connectedness, and alexithymia.
AB  - The present study was aimed at investigating the relationships among attachment
      styles, autonomy-connectedness (self-awareness, sensitivity to others, and
      capacity for managing new situations), alexithymia, and antisocial behavior among
      202 college students (67 men and 135 women). We were particularly interested in
      sex differences in the levels of these variables as well as their associations.
      Sex differences were expected in types of insecure attachment styles, patterns of
      autonomy-connectedness, and levels of self-reported antisocial and passive
      aggressive behavior. All expected sex differences were indeed found. Furthermore,
      the model that we hypothesized was partly confirmed: For men, anxious attachment
      had a stronger direct and positive effect on antisocial behavior than for women,
      and the positive effect of anxious attachment on passive-aggressive behavior was
      smaller for women than for men. Interestingly, capacity for managing new
      situations had a main and mediating effect on antisocial behavior. Sensitivity to
      others appeared as a mediator between anxious attachment style and passive
      aggressive behavior. Contrary to expectations, fantasizing (a component of
      alexithymia) had a strong, negative association with antisocial behavior. The
      results are discussed against the background of other recent findings concerning
      alexithymia and autonomy- connectedeness.

PMID- 17457848
TI  - The efficacy of cognitive-behavioral therapy and the problem of drop-out.
AB  - Treatment drop-out is a common problem in the everyday practice of psychotherapy.
      In the cognitive-behavioral psychology literature, there are scant data on drop
      out from therapy and the data available vary widely according to the definition
      of drop-out and the intensity of treatment. This study presents results obtained
      in the Behavioural Therapy Unit of the University of Barcelona. Of the 203
      patients seen in the unit, 89 (43.8%) dropped out, mostly in the early stages of
      the intervention. The most common reasons for this were low motivation and/or
      dissatisfaction with the treatment or the therapist (46.7%), external
      difficulties (40%), and patients' feeling of improvement (13.3%). Patients who
      dropped out differed from those who continued; they more often presented
      affective or eating disorders or problems with impulse control. The observed drop
      out rate is in line with figures reported for psychotherapy in general and by
      those studies which have considered cognitive-behavioral therapy in particular.

PMID- 17457849
TI  - Longitudinal relations between employment and depressive symptoms in low-income,
      suicidal African American women.
AB  - Unemployment and depression are problematic at both individual and societal
      levels, and research suggests that the two phenomena are related. More thorough
      and longitudinal analyses, particularly ones within low-income minority
      populations, are needed to guide the development of programs to increase
      employment in persons with mental health problems. The current study aimed to
      specify the relations over time between depressive symptoms and employment status
      within a sample of 46 low-income African American women participating in an
      intervention study for intimate partner violence and suicidal behavior.
      Hierarchical logistic regression analysis indicated that baseline levels of
      depressive symptoms predicted employment status at the end of a 10-week
      intervention period, controlling for baseline employment status. Chi-square
      analysis and qualitative analyses of trends in depression scores showed that
      changes in employment status during the 10-week intervention period predicted 6
      month and one-year follow-up levels of depressive symptoms. Results imply that,
      for women in the currently sampled population, depressive symptoms create
      vulnerability for job loss, but the ability to gain employment despite high
      levels of depressive symptoms is linked to lowered depression levels over the
      long term. Community programs assisting such women could therefore not just lower
      the vulnerability to job loss by treating depressive symptoms, but they could
      potentially lower long-term depression levels through interventions that enhance
      employability and motivation to pursue work.

PMID- 17457850
TI  - The cognitive nature of forgiveness: using cognitive strategies of primary
      appraisal and coping to describe the process of forgiving.
AB  - The present study investigated forgiveness in a traditional cognitive model of
      stress appraisal and coping and in a more recent model that includes the
      construct of low control stressors. One-hundred sixty six men and 168 women
      completed measures of forgiveness, primary stress appraisals, and coping
      strategies. For men, forgiveness was found to be positively associated with the
      use of challenge appraisals, and negatively associated with the use of loss
      appraisals and emotion-focused coping. For women, forgiveness was found to be
      positively associated with emotion-focused coping and acceptance, and negatively
      associated with avoidance. The results for women indicate that when forgiveness
      situations are conceptualized as low-control stressors, we are able to explain
      the relationships between forgiveness, appraisal, and coping. The results for men
      are broadly in line with a more traditional model of coping, which does not
      consider the construct of low control. Crucial differences in the ways that men
      and women appraise and cope with situations involving forgiveness are discussed.

PMID- 17457851
TI  - God's will, God's punishment, or God's limitations? Religious coping strategies
      reported by young adults living with serious mental illness.
AB  - Qualitative research has demonstrated that religious meaning-making coping,
      defined as attributions of a stressful life event that involve the sacred, is
      particularly relevant to persons with serious mental illness. However, recent
      research advances in the study of religious coping have yet to be employed in
      clinical samples. This longitudinal study examines religious meaning-making
      coping in a sample of 48 young adults diagnosed with schizophrenia or bipolar
      disorder over a one-year period. Young adults with mental illness generally
      reported using religious meaning-making coping in levels comparable to
      nonpsychiatric samples. Reports of benevolent religious reappraisals were
      associated with perceptions of positive mental health, whereas punishing God
      reappraisals and reappraisals of God's power were associated with self-reported
      distress and personal loss. Religious coping variables accounted for variation in
      adults' reports of psychiatric symptoms and personal loss one year later over and
      above demographic and global religious variables. Implications of findings for
      clinical practice are discussed.

PMID- 17457852
TI  - Undifferentiated hepatic sarcoma with cardiac extension.

PMID- 17457853
TI  - Liver biopsy results in patients with sickle cell disease on chronic
      transfusions: poor correlation with ferritin levels.
AB  - BACKGROUND: Chronic transfusions are effective in preventing stroke and other
      complications of sickle cell disease. The aim of this study was to determine
      whether serum ferritin levels correlated with liver iron content in sickle cell
      patients on chronic transfusion. PROCEDURE: Forty-four liver biopsy specimens
      from 38 patients with homozygous sickle cell anemia (HbSS) and one patient with
      sickle thalassemia receiving chronic transfusions were studied. Five patients
      underwent a second liver biopsy for follow up. Three ferritin measurements were
      used to calculate a mean for each patient. The association between serum ferritin
      levels and liver iron quantitation was measured using the Spearman rank
      correlation, and sensitivity and specificity were determined for selected
      threshold values of serum ferritin. RESULTS: Serum ferritin levels ranged from
      515 to 6076 ng/ml, liver iron concentration ranged from 1.8 to 67.97 mg/g dry
      weight. The amount of iron per gram liver dry weight was moderately correlated
      with serum ferritin values (r = 0.46). The correlation of duration of transfusion
      with serum ferritin (r = 0.40) and with liver iron content (r = 0.41) also
      indicated moderate correlation. Liver biopsy results led to changes in the
      management after 29/44 (66%) of the biopsies. Serum ferritin >/=2500 ng/ml
      predicted high liver iron content (>/=7 mg/g), with a sensitivity of 62.5% and a
      specificity of 77.8%. CONCLUSION: We found a poor correlation between serum
      ferritin levels and liver iron content (LIC). Despite being on chelation therapy,
      many patients on chronic transfusion had high levels of liver iron. Measurement
      of LIC is highly recommended in these patients.

PMID- 17457854
TI  - Initial testing of the VEGFR inhibitor AZD2171 by the pediatric preclinical
      testing program.
AB  - BACKGROUND: Inhibition of vascular endothelial growth factor mediated signaling
      shows promise as an antiangiogenic strategy for solid tumors. AZD2171 is a potent
      and relatively selective inhibitor of the vascular endothelial growth factor
      (VEGF) receptor family that is orally bioavailable. This study was designed to
      screen for antitumor activity of AZD2171 against the in vitro and in vivo
      childhood cancer preclinical models of the Pediatric Preclinical Testing Program
      (PPTP). PROCEDURES: AZD2171 was tested at concentrations from 0.1 nM to 1.0
      microM against the in vitro panel and was tested against the in vivo tumor panels
      using a 6-week exposure to daily gavage administration of AZD2171 (3 or 6 mg/kg)
      or vehicle. RESULTS: One of 22 cell lines evaluated was sensitive to AZD2171 in
      vitro (maximum concentration 1 microM). Evidence of in vivo antitumor activity
      (primarily tumor growth delay) was observed in 78% of solid tumor xenografts (3/3
      rhabdoid, 2/3 Wilms', 3/3 Ewing's, 5/5 rhabdomyosarcoma, 1/3 medulloblastoma, 2/4
      glioblastoma, 5/6 neuroblastoma, 4/5 osteosarcoma). Objective responses (both
      complete responses) were observed in two of 32 (6%) solid tumor xenografts (a
      rhabdoid xenograft and an osteosarcoma xenograft). No activity was observed
      against 7 acute lymphoblastic leukemia models. CONCLUSIONS: AZD2171 demonstrated
      broad tumor growth inhibition against the PPTP's solid tumor xenografts and much
      less commonly induced tumor regression. This pattern of in vivo activity,
      combined with the disassociation of in vitro and in vivo efficacy, are consistent
      with AZD2171 inhibiting growth of the PPTP's solid tumor xenografts primarily
      through an anti-angiogenesis mechanism of action.

PMID- 17457855
TI  - Reactive nonproliferative gliosis predominates in a chronic mouse model of
      glaucoma.
AB  - In many CNS diseases, proliferation becomes dysregulated; cells divide and
      participate in pathological processes. Gliosis is a fundamental CNS response to
      trauma or disease in which cell hypertrophy and proliferation play prominent
      roles. The DBA/2J mouse is a glaucoma model in which mice experience gliosis
      concomitant with raised intraocular pressure that leads to a slow and progressive
      retinal ganglion cell axonopathy. We sought to determine if glaucomatous changes
      in DBA/2 retina would alter the regulation of cell proliferation, specifically in
      relation to retinal glia. Astrocyte and Muller glia populations within DBA/2
      retina upregulated glial fibrillary acidic protein mRNA and protein compared with
      C57Bl/6; microglial cell number increased twofold from 4 to 10 months. Various
      bromodeoxyuridine (BrdU) injection paradigms were used to label dividing cells in
      DBA/2 and C57Bl/6 retina at 4 and 10 months of age. Very modest cell division in
      the retina, primarily in ganglion cell and inner nuclear layers, was observed at
      all ages. Immunohistochemistry indicated cell turnover primarily of NG2+
      pericytes and Iba1+ microglia; astrocytes and Muller glia did not proliferate.
      There were no significant differences in BrdU+ cell numbers in 4 and 10-month-old
      retina, though 4-month retina had generally fewer BrdU+ cells than 10-month.
      C57Bl/6 retinas had fewer BrdU+ cells than DBA/2 retinas at all ages. These data
      show that, in contrast to gliosis in other CNS trauma and neurodegenerative
      diseases, glaucomatous changes in retina do not include substantive cell
      proliferation. Retinal changes in a chronic model of glaucoma engender a
      reactive, not proliferative, gliosis response.

PMID- 17457856
TI  - Hepatectomy vs. liver transplantation: a combination rather than an opposition.

PMID- 17457857
TI  - Use of extracorporeal albumin dialysis for erythropoietic protoporphyria.

PMID- 17457858
TI  - Recurrent hepatitis C: worse outcomes established, interventions still
      inadequate.

PMID- 17457859
TI  - Antiplatelet medication after liver transplantation: does it affect outcome?

PMID- 17457860
TI  - Salvage living donor liver transplantation after prior liver resection for
      hepatocellular carcinoma.
AB  - Salvage liver transplantation has been performed for recurrent hepatocellular
      carcinoma (HCC) or deterioration of liver function after primary liver resection.
      Because prior liver resection per se is an unfavorable condition for living donor
      liver transplantation (LDLT), we assessed the technical feasibility of LDLT after
      prior hepatectomy, and we compared the outcome of salvage LDLT with that of
      primary LDLT in HCC patients. Of 342 patients with HCC, 17 (5%) underwent salvage
      LDLT, with 5 having undergone prior major liver resection and 12 prior minor
      resection. During salvage LDLT, 12 patients received right lobe grafts, 3
      received left lobe grafts, and 2 received dual grafts. There was 1 incident
      (5.9%) of perioperative mortality. Recipient operation time was not prolonged in
      patients undergoing salvage LDLT, but bleeding complications occurred more
      frequently than in patients undergoing primary LDLT. Overall survival rates after
      salvage LDLT were similar to those after primary LDLT, especially when the extent
      of recurrent tumor was within the Milan criteria. These results indicate that
      every combination of prior hepatectomy and living donor liver graft is feasible
      for patients undergoing salvage LDLT, and the acceptable extent of HCC for
      salvage LDLT is equivalent to that for primary LDLT.

PMID- 17457861
TI  - In vivo imaging of changes in tumor oxygenation during growth and after
      treatment.
AB  - A novel procedure for in vivo imaging of the oxygen partial pressure (pO2) in
      implanted tumors is reported. The procedure uses electron paramagnetic resonance
      imaging (EPRI) of oxygen-sensing nanoprobes embedded in the tumor cells. Unlike
      existing methods of pO2 quantification, wherein the probes are physically
      inserted at the time of measurement, the new approach uses cells that are
      preinternalized (labeled) with the oxygen-sensing probes, which become
      permanently embedded in the developed tumor. Radiation-induced fibrosarcoma (RIF
      1) cells, internalized with nanoprobes of lithium octa-n-butoxy-naphthalocyanine
      (LiNc-BuO), were allowed to grow as a solid tumor. In vivo imaging of the growing
      tumor showed a heterogeneous distribution of the spin probe, as well as
      oxygenation in the tumor volume. The pO2 images obtained after the tumors were
      exposed to a single dose of 30-Gy X-radiation showed marked redistribution as
      well as an overall increase in tissue oxygenation, with a maximum increase 6 hr
      after irradiation. However, larger tumors with a poorly perfused core showed no
      significant changes in oxygenation. In summary, the use of in vivo EPR technology
      with embedded oxygen-sensitive nanoprobes enabled noninvasive visualization of
      dynamic changes in the intracellular pO2 of growing and irradiated tumors.

PMID- 17457862
TI  - T1-weighted magnetic resonance imaging shows fatty deposition after myocardial
      infarction.
AB  - Pathologic studies have shown an increased lipid content in areas of myocardial
      infarction (MI). We sought to show the ability of precontrast T1-weighted MRI to
      noninvasively detect fat deposition in MI and show its association with infarct
      age. Thirty-two patients with MI were studied. Precontrast inversion-recovery
      (IR) cine steady-state free precession (SSFP) imaging was used to generate both
      fat- and muscle-nulled images to locate areas of fat deposition in the left
      ventricular (LV) myocardium. Postcontrast delayed hyperenhanced (DHE) imaging was
      also performed. Image contrast in regions of MI on precontrast images and
      postcontrast DHE images was measured. The association of image contrast with
      infarct age was determined by means of correlations and Student's t-test. We
      found a significant association between infarct age and image contrast in both
      fat- and muscle-nulled images. Precontrast T1-weighted MRI is a promising method
      for detecting myocardial fat deposition in chronic MI, and can be used to assess
      myocardial infarct age.

PMID- 17457863
TI  - Reduction of transmitter B1 inhomogeneity with transmit SENSE slice-select
      pulses.
AB  - Parallel transmitter techniques are a promising approach for reducing transmitter
      B1 inhomogeneity due to the potential for adjusting the spatial excitation
      profile with independent RF pulses. These techniques may be further improved with
      transmit sensitivity encoding (SENSE) methods because the sensitivity information
      in pulse design provides an excitation that is inherently compensated for
      transmitter B1 inhomogeneity. This paper presents a proof of this concept using
      transmit SENSE 3D tailored RF pulses designed for small flip angles. An eight
      channel receiver coil was used to mimic parallel transmission for brain imaging
      at 3T. The transmit SENSE pulses were based on the fast-k(z) design and produced
      5-mm-thick slices at a flip angle of 30 degrees with only a 4.3-ms pulse length.
      It was found that the transmit SENSE pulses produced more homogeneous images than
      those obtained from the complex sum of images from all receivers excited with a
      standard RF pulse.

PMID- 17457864
TI  - Fast mapping of the T2 relaxation time of cerebral metabolites using proton echo
      planar spectroscopic imaging (PEPSI).
AB  - Metabolite T2 is necessary for accurate quantification of the absolute
      concentration of metabolites using long-echo-time (TE) acquisition schemes.
      However, lengthy data acquisition times pose a major challenge to mapping
      metabolite T2. In this study we used proton echo-planar spectroscopic imaging
      (PEPSI) at 3T to obtain fast T2 maps of three major cerebral metabolites: N
      acetyl-aspartate (NAA), creatine (Cre), and choline (Cho). We showed that PEPSI
      spectra matched T2 values obtained using single-voxel spectroscopy (SVS). Data
      acquisition for 2D metabolite maps with a voxel volume of 0.95 ml (32 x 32 image
      matrix) can be completed in 25 min using five TEs and eight averages. A
      sufficient spectral signal-to-noise ratio (SNR) for T2 estimation was validated
      by high Pearson's correlation coefficients between logarithmic MR signals and TEs
      (R2 = 0.98, 0.97, and 0.95 for NAA, Cre, and Cho, respectively). In agreement
      with previous studies, we found that the T2 values of NAA, but not Cre and Cho,
      were significantly different between gray matter (GM) and white matter (WM; P <
      0.001). The difference between the T2 estimates of the PEPSI and SVS scans was
      less than 9%. Consistent spatial distributions of T2 were found in six healthy
      subjects, and disagreement among subjects was less than 10%. In summary, the
      PEPSI technique is a robust method to obtain fast mapping of metabolite T2.

PMID- 17457865
TI  - Carotid plaque classification: defining the certainty with which plaque
      components can be differentiated.
AB  - Multicontrast-weighted MRI has the potential to become a powerful tool for
      assessment of atherosclerotic plaque. However, similarities in MR properties
      across plaque components limit the certainty with which these components can be
      differentiated. An understanding of MRI's underlying limitations in
      distinguishing atherosclerotic plaque components, and optimization of key
      parameters (including the set of components investigated and contrast weightings
      used) are required. In this study we analyzed endarterectomy specimens using
      multicontrast MRI and compared the results with matching histological findings to
      determine the probability of error, an unbiased measure of the underlying error
      caused by similarity in the spectral characteristics of components. The total
      error was >40% when five distinct components were investigated, but this was
      halved when components with similar functions and intensities were grouped
      together. When three contrast weightings were used to view plaque, diffusion
      weighted imaging (DWI) proved valuable for separating hemorrhage from necrotic
      core, and "hemorrhage + necrotic" from "loose connective tissue + fibrous
      tissue." A two-way interaction between contrast weightings and components
      demonstrated that the value of a contrast can be exploited or marginalized
      depending on the choice of contrast weightings used.

PMID- 17457866
TI  - Geographic disparities in deceased donor liver transplantation within a single
      UNOS region.
AB  - Although the Model for End-Stage Liver Disease (MELD) scoring system has improved
      the ability to measure medical urgency for transplantation, geographic
      disparities in the probability of being delisted as a result of complications of
      end-stage liver disease or death and in the probability of orthotopic liver
      transplantation (OLT) remain. The purpose of the current study was to identify
      factors associated with these variations among donor service areas (DSAs) in one
      United Network for Organ Sharing (UNOS) region. Data for 2,948 candidates listed
      for OLT within 4 DSAs in UNOS region 4 between February 2002 and November 2005
      were obtained from UNOS. Multivariate regression models were used to identify
      study factors associated with delisting (due to deterioration or death) and
      likelihood of OLT. After risk adjustment for candidate characteristics, those
      listed in DSA-3 and DSA-4 were at significantly higher risk of delisting than
      candidates listed in DSA-2 (hazard ratio, 1.22 and 1.10 vs. 0.87 for DSA-2; P =
      0.01 and 0.05, respectively). In addition, the likelihood of OLT was
      significantly higher for candidates listed in DSA-1 than in DSA-2, DSA-3 or DSA-4
      (hazard ratio, 1.00 compared with 0.45, 0.77, and 0.51; P < 0.001 for all
      pairwise comparisons). Despite the implementation of the MELD system, great
      geographic disparities exist in the likelihood of delisting and for OLT,
      suggesting the need for further refinement in regional allocation strategies.

PMID- 17457867
TI  - Perioperative coagulation management in a patient with afibrinogenemia undergoing
      liver transplantation.
AB  - Afibrinogenemia is a rare hereditary coagulation disorder characterized by a
      propensity toward bleeding. A 21-year-old Hispanic woman with afibrinogenemia
      developed ascites, a distended abdomen, an enlarged liver, scleral icterus, and
      umbilical vein and abdominal wall vein distension. Computed tomography (CT) scan
      showed occlusion of the hepatic veins and the infrahepatic vena cava consistent
      with Budd-Chiari syndrome. These developments led to her evaluation for, and
      placement on, the liver transplantation waiting list. The patient's unmeasurable
      international normalized ratio (INR) artifactually increased her Model for End
      Stage Liver Disease (MELD) score to 40. Immediately before transplant surgery, an
      initial thrombelastogram (TEG) showed a flat line, indicating a complete lack of
      fibrin clot formation. Preoperatively, 20 units of cryoprecipitate were infused.
      The first intraoperative TEG demonstrated a tracing consistent with normal clot
      formation. Coagulation studies normalized with the newly functioning liver. The
      liver transplantation appears to have corrected the fibrinogen deficiency,
      presumably limiting the chance of recurrent Budd-Chiari syndrome. This case
      report discusses the essential role of fibrinogen in the coagulation cascade, as
      visualized by thrombelastography, and exposes the interplay between plasma
      fibrinogen and thrombin levels, which determine coagulation or fibrinolysis.

PMID- 17457868
TI  - Urinary ethyl glucuronide testing detects alcohol consumption in alcoholic liver
      disease patients awaiting liver transplantation.
AB  - This study compared measurement of urinary ethyl glucuronide (EtG), a conjugated
      minor ethanol metabolite with a longer detection window than ethanol itself, with
      breath alcohol testing and self-report as ways to disclose recent drinking by 18
      liver transplant candidates with an alcoholic liver disease diagnosis that
      underwent an addiction group therapy program. At each therapy session, patients
      were questioned about any alcohol consumption in the intervening time, and they
      also performed a mandatory breath alcohol test, while observed urine samples for
      measurement of EtG were delivered on a voluntary basis. None of the patients ever
      admitted to intake of alcohol, and only 1 of 127 breath alcohol tests turned out
      positive. However, 9 patients showed positive EtG results in 24 (49%) of 49 urine
      samples. The individual frequency of urine samples being positive for EtG ranged
      from 22% to 100% with a mean value of 57%. Because 6 patients refused to provide
      urine on a total of 18 occasions, alcohol use might have been even more common.
      These results underscore the uncertainty of self-report data and the low
      sensitivity of breath alcohol testing as ways to disclose recent drinking, and
      underline the necessity of introducing sensitive and specific objective measures
      of recent alcohol consumption, such as EtG, in the transplantation setting.

PMID- 17457869
TI  - Combined liver-kidney transplantation in glycogen storage disease Ia: a case
      beyond the guidelines.
AB  - Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disorder due to
      hepatic glucose-6-phosphatase deficiency. Although great progress has been made
      in managing affected patients, severe hypoglycemia, lactic acidosis,
      hyperlipidemia, hepatic cytolysis, and impaired kidney function are frequent.
      Liver transplantation is the only radical treatment, for which the main
      indications are hepatic adenomatosis, hepatocellular carcinoma, or severe hepatic
      dysfunction. We present the case of a patient with end-stage renal disease
      without focal hepatic lesions and with moderate hepatic metabolic control, and we
      explain how combined liver-kidney transplantation (LKT) made it possible to
      correct the metabolic defects responsible for the impaired glucose homeostasis,
      liberalize the diet, and give birth to a healthy child after an uneventful
      pregnancy. Patients with end-stage renal disease that resulted from GSD Ia should
      be considered for LKT even in the absence of hepatic lesions with the aim of
      improving their quality of life.

PMID- 17457870
TI  - 3T MR of the prostate: reducing susceptibility gradients by inflating the
      endorectal coil with a barium sulfate suspension.
AB  - Most prostate MRI/MRS examinations are performed with an endorectal coil inflated
      with air, leading to an air-tissue interface that induces magnetic susceptibility
      gradients within the gland. Inflation of the coil with a barium sulfate
      suspension is described and compared to inflation with air or liquid
      perfluorocarbon (PFC). The B(0) field in the prostate gland was mapped for five
      healthy volunteers when the endorectal coil was inflated with each of the three
      agents. A marked decrease in the posterior-anterior (P-A) field gradient and a
      significant improvement in field homogeneity were evident in the presence of a
      barium suspension and PFC relative to air. MRS data acquired from the prostate
      gland in the presence of air, PFC, and a barium suspension in the endorectal coil
      showed similar trends, demonstrating improvement in line-widths and spectral
      resolution when the barium suspension or the PFC were inflating the endorectal
      coil. On this basis we conclude that a barium suspension provides an available,
      cheap, and safe alternative to PFC, and we suggest that inflating the endorectal
      coil with a barium suspension should be considered for prostate MR studies,
      especially at high field strengths (such as 3T).

PMID- 17457871
TI  - Improving k-t SENSE by adaptive regularization.
AB  - The recently proposed method known as k-t sensitivity encoding (SENSE) has
      emerged as an effective means of improving imaging speed for several dynamic
      imaging applications. However, k-t SENSE uses temporally averaged data as a
      regularization term for image reconstruction. This may not only compromise
      temporal resolution, it may also make some of the temporal frequency components
      irrecoverable. To address that issue, we present a new method called
      spatiotemporal domain-based unaliasing employing sensitivity encoding and
      adaptive regularization (SPEAR). Specifically, SPEAR provides an improvement over
      k-t SENSE by generating adaptive regularization images. It also uses a variable
      density (VD), sequentially interleaved k-t space sampling pattern with reference
      frames for data acquisition. Simulations based on experimental data were
      performed to compare SPEAR, k-t SENSE, and several other related methods, and the
      results showed that SPEAR can provide higher temporal resolution with
      significantly reduced image artifacts. Ungated 3D cardiac imaging experiments
      were also carried out to test the effectiveness of SPEAR, and real-time 3D short
      axis images of the human heart were produced at 5.5 frames/s temporal resolution
      and 2.4 x 1.2 x 8 mm3 spatial resolution with eight slices.

PMID- 17457872
TI  - Spectral phase-corrected GRAPPA reconstruction of three-dimensional echo-planar
      spectroscopic imaging (3D-EPSI).
AB  - MR spectroscopic (MRS) images from a large volume of brain can be obtained using
      a 3D echo-planar spectroscopic imaging (3D-EPSI) sequence. However, routine
      applications of 3D-EPSI are still limited by a long scan time. In this
      communication, a new approach termed "spectral phase-corrected generalized
      autocalibrating partially parallel acquisitions" (SPC-GRAPPA) is introduced for
      the reconstruction of 3D-EPSI data to accelerate data acquisition while
      preserving the accuracy of quantitation of brain metabolites. In SPC-GRAPPA,
      voxel-by-voxel spectral phase alignment between metabolite 3D-EPSI from
      individual coil elements is performed in the frequency domain, utilizing the
      whole spectrum from interleaved water reference 3D-EPSI for robust estimation of
      the zero-order phase correction. The performance of SPC-GRAPPA was compared with
      that of fully encoded 3D-EPSI and conventional GRAPPA. Analysis of whole-brain 3D
      EPSI data reconstructed by SPC-GRAPPA demonstrates that SPC-GRAPPA with an
      acceleration factor of 1.5 yields results very similar to those obtained by fully
      encoded 3D-EPSI, and is more accurate than conventional GRAPPA.

PMID- 17457873
TI  - Direct magnetic resonance imaging of histological tissue samples at 3.0T.
AB  - Direct imaging of a histological slice is challenging. The vast difference in
      dimension between planar size and the thickness of histology slices would require
      an RF coil to produce a uniform RF magnetic (B1) field in a 2D plane with minimal
      thickness. In this work a novel RF coil designed specifically for imaging a
      histology slice was developed and tested. The experimental data demonstrate that
      the coil is highly sensitive and capable of producing a uniform B1 field
      distribution in a planar region of histological slides, allowing for the
      acquisition of high-resolution T2 images and T2 maps from a 60-microm-thick
      histological sample. The image intensity and T2 distributions were directly
      compared with histological staining of the relative iron concentration of the
      same slice. This work demonstrates the feasibility of using a microimaging
      histological coil to image thin slices of pathologically diseased tissue to
      obtain a precise one-to-one comparison between stained tissue and MR images.

PMID- 17457874
TI  - Optimal methods for the preservation of cartilage samples in MRI and correlative
      biochemical studies.
AB  - MRI studies of cartilage require the prevention of sample degradation before and
      during scanning and during shipment for correlative studies. Methods to achieve
      this include immersion in protease inhibitors (PIs), refrigeration, and freezing.
      In this study, bovine nasal cartilage (BNC) samples were stored in Dulbecco's
      phosphate-buffered saline (DPBS), DPBS with standard PIs, or PI solution with
      GM6001, a potent metalloproteinase inhibitor. For each buffer, three samples were
      scanned at +4 degrees C and stored at +4 degrees C or at -20 degrees C with
      thawing prior to imaging. T2 and magnetization transfer (MT) rate, km, were
      measured weekly over 4 months, after which time water and glycosaminoglycan (GAG)
      contents were compared with those of matching tissue excised pre-storage. Samples
      in DPBS exhibited increased T2 (+33.6% after 1 month at +4 degrees C, P = 0.040)
      and decreased km (-20.6%, P = 0.004), while refrigeration in DPBS with PI and
      GM6001 yielded good stability (T2: +2.7%, P = 0.874; km: -4.2%, P = 0.654 after
      108 days at +4 degrees C). Water content increased while GAG content markedly
      decreased in all samples. Thus, stability in cartilage MRI parameters can be
      optimized with appropriate storage conditions, but storage time should
      nonetheless be minimized.

PMID- 17457875
TI  - Perfusion MRI with radial acquisition for arterial input function assessment.
AB  - Quantification of myocardial perfusion critically depends on accurate arterial
      input function (AIF) and tissue enhancement curves (TECs). Except at low doses,
      the AIF is inaccurate because of the long saturation recovery time (SRT) of the
      pulse sequence. The choice of dose and SRT involves a trade-off between the
      accuracy of the AIF and the signal-to-noise ratio (SNR) of the TEC. Recent
      methods to resolve this trade-off are based on the acquisition of two data sets:
      one to accurately estimate the AIF, and one to find the high-SNR TEC. With radial
      k-space sampling, a set of images with varied SRTs can be reconstructed from the
      same data set, allowing an accurate assessment of the AIF and TECs, and their
      conversion to contrast agent (CA) concentration. This study demonstrates the
      feasibility of using a radial acquisition for quantitative myocardial perfusion
      imaging.

PMID- 17457876
TI  - Clinical multishot DW-EPI through parallel imaging with considerations of
      susceptibility, motion, and noise.
AB  - Geometric distortions and poor image resolution are well known shortcomings of
      single-shot echo-planar imaging (ss-EPI). Yet, due to the motion immunity of ss
      EPI, it remains the most common sequence for diffusion-weighted imaging (DWI).
      Moreover, both navigated DW interleaved EPI (iEPI) and parallel imaging (PI)
      methods, such as sensitivity encoding (SENSE) and generalized autocalibrating
      parallel acquisitions (GRAPPA), can improve the image quality in EPI. In this
      work, DW-EPI accelerated by PI is proposed as a self-calibrated and unnavigated
      form of interleaved acquisition. The PI calibration is performed on the b = 0
      s/mm2 data and applied to each shot in the rest of the DW data set, followed by
      magnitude averaging. Central in this study is the comparison of GRAPPA and SENSE
      in the presence of off-resonances and motion. The results show that GRAPPA is
      more robust than SENSE against both off-resonance and motion-related artifacts.
      The SNR efficiency was also investigated, and it is shown that the SNR/scan time
      ratio is equally high for one- to three-shot high-resolution diffusion scans due
      to the shortened EPI readout train length. The image quality improvements without
      SNR efficiency loss, together with motion tolerance, make the GRAPPA-driven DW
      EPI sequence clinically attractive.

PMID- 17457877
TI  - T2 measurement of the human myocardium using a T2-prepared transient-state
      TrueFISP sequence.
AB  - A fast and motion-insensitive technique suitable for myocardial BOLD contrast
      imaging is presented. The method, termed T2-TrueFISP, combines T2 magnetization
      preparation with steady-state free precession (SSFP) imaging for T2 relaxation
      mapping of the myocardium in healthy volunteers. The T2 contrast-to-noise ratio
      (CNR) was optimized with the use of transient-state TrueFISP readout and half
      Fourier readout with linear phase encoding. Single-slice myocardial T2-weighted
      image was obtained within one heartbeat, and a single slice T2 map of the
      myocardium was obtained in under 5-7 s. A respiratory navigator-gating method was
      incorporated for serial measurements and signal averaging, with the subjects
      breathing freely. The mean myocardial T2 relaxation time measured in 12 healthy
      volunteers was 54 +/- 5.7 ms. Regional variations of T2 values across the
      myocardium were 7%. Temporal variations across serial T2 measurements in a
      transmural region covering approximately 0.5 cc of the left ventricular (LV) wall
      were 3.6% without signal averaging (number of excitations (NEX) = 1) and 1.7%
      with signal averaging (NEX = 10). According to our preliminary results, the T2
      TrueFISP method is expected to provide a robust and sensitive tool for clinical
      application of myocardial BOLD contrast imaging.

PMID- 17457878
TI  - RF refocused echoes of J-coupled spin systems: effects on RARE-based
      spectroscopic imaging.
AB  - A numerical simulation tool was developed to calculate the echo amplitudes of J
      coupled resonances within a series of radiofrequency (RF) refocused echoes. The
      signal modulation due to J-coupling in rapid acquisition with relaxation
      enhancement (RARE) is suppressed only when the inverse of the pulse interval
      (tau) is large compared to both the chemical shift (CS) difference (Deltadelta)
      of the coupled spins and the coupling constant. In contrast, the echo amplitudes
      in ultrafast low-flip-angle RARE (U-FLARE) oscillate around a quasi-steady-state
      value that is greater than zero (neglecting relaxation and diffusion) even when
      Deltadelta > 1/tau. The flip-angle distribution over the measured slice caused by
      the use of Gaussian-shape slice-selective refocusing pulses further reduces the
      echo oscillations. When the pulse interval falls short of the fast pulse rate
      regime, spectroscopic U-FLARE provides an improved spatial impulse response in
      the phase-encoding (PE) direction compared to spectroscopic RARE.

PMID- 17457879
TI  - Intuitive design guidelines for fast spin echo imaging with variable flip angle
      echo trains.
AB  - We present a simple and intuitive means for determining the flip angles (FAs)
      required for smooth transitions between static pseudo steady states (SPSSs) in
      fast spin echo (FSE) imaging with variable FA (VFA) echo trains. We demonstrate
      the effectiveness of single and multiple transition pulses to successfully vary
      refocusing FAs while retaining high signal levels. The graphical interpretation
      presented here is consistent with previous analytical techniques and permits
      accurate signal-intensity predictions along the echo train.

PMID- 17457880
TI  - T2-prepared SSFP improves diagnostic confidence in edema imaging in acute
      myocardial infarction compared to turbo spin echo.
AB  - T2-weighted MRI of edema in acute myocardial infarction (MI) provides a means of
      differentiating acute and chronic MI, and assessing the area at risk of
      infarction. Conventional T2-weighted imaging of edema uses a turbo spin-echo
      (TSE) readout with dark-blood preparation. Clinical applications of dark-blood
      TSE methods can be limited by artifacts such as posterior wall signal loss due to
      through-plane motion, and bright subendocardial artifacts due to stagnant blood.
      Single-shot imaging with a T2-prepared SSFP readout provides an alternative to
      dark-blood TSE and may be conducted during free breathing. We hypothesized that
      T2-prepared SSFP would be a more reliable method than dark-blood TSE for imaging
      of edema in patients with MI. In patients with MI (22 acute and nine chronic MI
      cases), T2-weighted imaging with both methods was performed prior to contrast
      administration and delayed-enhancement imaging. The T2-weighted images using TSE
      were nondiagnostic in three of 31 cases, while six additional cases rated as
      being of diagnostic quality yielded incorrect diagnoses. In all 31 cases the T2
      prepared SSFP images were rated as diagnostic quality, correctly differentiated
      acute or chronic MI, and correctly determined the coronary territory. Free
      breathing T2 prepared SSFP provides T2-weighted images of acute MI with fewer
      artifacts and better diagnostic accuracy than conventional dark-blood TSE.

PMID- 17457881
TI  - Reconstruction of undersampled dynamic images by modeling the motion of object
      elements.
AB  - Dynamic MRI is restricted due to the time required to obtain enough data to
      reconstruct the image sequence. Several undersampled reconstruction techniques
      have been proposed to reduce the acquisition time. In most of these techniques
      the nonacquired data are recovered by modeling the temporal information as
      varying pixel intensities represented in time or in temporal frequencies. Here we
      propose a new approach that recovers the missing data through a motion estimation
      of the object elements ("obels," or pieces of tissue) of the image. This method
      assumes that an obel displacement through the sequence has lower bandwidth than
      fluctuations in pixel intensities caused by the motion, and thus it can be
      modeled with fewer parameters. Preliminary results show that this technique can
      effectively reconstruct (with root mean square (RMS) errors below 4%) cardiac
      images and joints with undersampling factors of 8 and 4, respectively. Moreover,
      in the reconstruction process an approximation of the motion vectors is obtained
      for each obel, which can be used to quantify dynamic information. In this method
      the motion need not be confined to a part of the field of view (FOV) or to a
      portion of the temporal frequency. It is appropriate for dynamic studies in which
      the obels' motion model has fewer parameters than the number of acquired samples.

PMID- 17457882
TI  - High-resolution chemical shift imaging for the assessment of intramuscular
      lipids.
AB  - A new high-resolution MRSI technique was used to measure extracellular lipids
      (EMCL), intracellular lipids (IMCL), and total muscle lipids (TML). The purpose
      of this study was to assess the feasibility and reproducibility of this new
      technique. This study also compared results obtained from small regions of
      interest (ROIs) vs. a summation of a large ROI of voxels representing the total
      soleus or anterior tibialis (TA) muscles. Eight volunteers were studied with the
      use of a conventional single-slice MR spectroscopic imaging (MRSI) sequence run
      with the following parameters: TR = 145.9 ms, FOV = 16 cm, slice thickness = 1
      cm, and 64 x 64 phase encodes. EMCL, IMCL, and TML values from the small ROIs
      proved to be reproducible (coefficient of variation (CV) = 7.8-13.8% for soleus,
      and 8.2-18% for TA). EMCL, IMCL, and TML values from the larger soleus ROI proved
      to be reproducible (CV = 7.3-16.1%), whereas the larger TA ROIs were less
      reproducible. The small and larger soleus ROIs produced statistically equivalent
      measures of EMCL and TML per unit area. However, the small soleus and TA ROIs
      showed a trend toward yielding different IMCL contents as compared to the larger
      ROIs. This study demonstrates that high-resolution 1H MRSI of the calf muscle is
      feasible and can reproducibly measure EMCL, IMCL, and TML.

PMID- 17457883
TI  - Complex data analysis in high-resolution SSFP fMRI.
AB  - In transition-band steady-state free precession (SSFP) functional MRI (fMRI),
      functional contrast originates from a bulk frequency shift induced by a
      deoxygenated hemoglobin concentration change in the activated brain regions. This
      frequency shift causes a magnitude and/or phase-signal change depending on the
      off-resonance distribution of a voxel in the balanced-SSFP (bSSFP) profile.
      However, in early low-resolution studies, only the magnitude signal activations
      were shown. In this paper the task-correlated phase-signal change is presented in
      a high-resolution (1 x 1 x 1 mm3) study. To include this phase activation in a
      functional analysis, a new complex domain data analysis method is proposed. The
      results show statistically significant phase-signal changes in a large number of
      voxels comparable to that of the magnitude-activated voxels. The complex-data
      analysis method successfully includes these phase activations in the activation
      map and thus provides wider coverage compared to magnitude-data analysis results.

PMID- 17457884
TI  - Self-calibrated GRAPPA method for 2D and 3D radial data.
AB  - A fast parallel MRI (pMRI) reconstruction method is presented for 2D and 3D
      radial trajectories. A limitation of the radial generalized autocalibrating
      partially parallel acquisitions (GRAPPA) method is the need to acquire training
      data prior to the actual scan. This can be eliminated by the use of self
      calibration when synthesizing the missing data for each coil reconstruction. The
      training data for each coil are estimated by multiplying the conventionally
      reconstructed composite image, which contains the aliasing artifacts from
      undersampling, with each coil's spatial sensitivity profile. An estimate of the
      individual receiver spatial sensitivity profiles is obtained from the k-space
      data that fulfill the Nyquist sampling criterion. The frequency domain
      representation of the training data is then calculated at the acquired k-space
      sample points and at the unacquired locations at which we desire to synthesize k
      space data. Fitting the acquired k-space samples to the unacquired points creates
      reconstruction weights that are used to synthesize unacquired radial lines. The
      in vivo feasibility of the method for 2D radial trajectories is illustrated with
      an example of 2D abdominal imaging. Preliminary results obtained after applying
      the method on a 3D radial steady-state free precession (SSFP) data set are also
      demonstrated.

PMID- 17457885
TI  - Can antiplatelet prophylaxis reduce the incidence of hepatic artery thrombosis
      after liver transplantation?
AB  - To ascertain whether postoperative antiplatelet therapy could reduce the
      incidence of hepatic artery thrombosis (HAT) after liver transplantation (LT),
      838 consecutive adult whole-graft LTs performed from April 1986 to August 2005
      that survived beyond the first postoperative month were reviewed. Antiplatelet
      prophylaxis with aspirin (100 mg per day) was given following 236 LTs; the median
      starting time was 8 postoperative days (range, 1 to 29 days). Early HAT was
      observed in 29 cases. The median time of presentation was 5 postoperative days
      (range, 1-28 days), and the effect of aspirin on this type of complication was
      therefore not assessable. A total of 14 cases of late HAT were observed (1.67 %).
      The median time of presentation was 500.5 days (range, 50-2,405 days). Late HAT
      occurred in 1 out of 236 (0.4 %) patients who were maintained under antiplatelet
      prophylaxis and in 13 out of 592 (2.2 %) who did not receive prophylaxis (P =
      0.049). Risk factors for late HAT (grafts retrieved from donors who died of
      cerebrovascular accident and/or use of iliac conduit at transplantation) were
      present in 498 LTs: in this group the incidence of late HAT was significantly
      higher among cases who did not receive prophylaxis (12/338 vs 1/160; p = 0.037).
      There were no hemorrhagic complications associated with the use of aspirin. In
      conclusion,antiplatelet prophylaxis can effectively reduce the incidence of late
      HAT after LT, particularly in those patients at risk for this complication.

PMID- 17457887
TI  - Conversion to sirolimus-based immunosuppression in maintenance liver
      transplantation patients.
AB  - Sirolimus (SRL) has been proposed to replace calcineurin inhibitors (CNI) in case
      of CNI-induced toxicity. The aim of this study was to evaluate the efficacy and
      safety of conversion from CNI to SRL in maintenance liver transplantation (LT)
      patients. Between 2002 and 2006, conversion was performed in 48 patients (17
      female, 31 male; mean age 57 +/- 10 yr) after a median delay of 19.4 months
      (range 0.2-173 months) after LT. Indication for conversion was renal impairment
      (RI) (78%), CNI neurotoxicity (13%), or post-LT cancer (9%). Median follow-up was
      22.6 +/- 11 months. Median SRL dosage and trough levels were 2.4 +/- 1.3 mg and
      8.1 +/- 2.7 microg/L. Immunosuppression consisted of SRL alone (33%), or SRL +
      mycophenolate mofetil (MMF) (39%), SRL + prednisone (15%), SRL + CNI (4%), or SRL
      + MMF + prednisone (8%). Mean glomerular filtration rate (GFR) improved from 33
      to 48 mL/minute in patients with severe RI (P = 0.022) and from 56 to 74
      mL/minute in patients with moderate RI (P = 0.0001). After conversion, main
      complications were albuminuria (36%), hyperlipidemia (49%), dermatitis (14%),
      edema (14%), oral ulcers (12%), joint pain (4%), infection (2%), and pneumonia
      (2%). Acute rejection (AR) occurred in 17% of the patients. SRL was withdrawn in
      17% of the patients. In conclusion, conversion from CNI to SRL is safe and is
      associated with significant renal function improvement.

PMID- 17457889
TI  - Neuronal PAS domain protein 1 regulates tyrosine hydroxylase level in
      dopaminergic neurons.
AB  - Catecholamines (dopamine, norepinephrine, and epinephrine) are all synthesized
      from a common pathway in which tyrosine hydroxylase (TH) is the rate-limiting
      enzyme. Dopamine is the main neurotransmitter present in dopaminergic neurons of
      the ventral midbrain, where dysfunction of these neurons can lead to Parkinson's
      disease and schizophrenia. Neuronal PAS domain protein 1 (NPAS1) was identified
      as one of the genes up-regulated during dopaminergic MN9D cell differentiation.
      We found that there was a corresponding decrease in TH level during MN9D
      differentiation. Overexpression and siRNA experiments revealed that NPAS1, in
      concert with ARNT, negatively regulates the expression of TH and that this
      regulation is mediated by a direct binding of NPAS1 on the TH promoter.
      Expression studies also confirmed a decrease in TH level in the ventral midbrain
      during mouse development, concomitant with an increase in NPAS1 level. These
      results suggest that NPAS1 plays a novel and important role in regulating TH
      level of dopaminergic neurons in the ventral midbrain during development.

PMID- 17457891
TI  - Optical coherence tomography: expanding use in the bile duct.

PMID- 17457890
TI  - Venous outflow reconstruction with surgically reopened obliterated umbilical vein
      in domino liver transplantation.

PMID- 17457893
TI  - MMF to EC-MPS conversion: what makes the difference?

PMID- 17457897
TI  - Pediatric hepatopulmonary syndrome is seen with polysplenia/interrupted inferior
      vena cava and without cirrhosis.
AB  - Hepatopulmonary syndrome (HPS) is a triad of liver dysfunction, hypoxemia, and
      intrapulmonary vascular dilatation. We describe the prevalence and clinical
      features of HPS at a pediatric liver transplant center. Patients referred to
      Children's Healthcare of Atlanta/Emory University transplant program from
      February 1999 to May 2005 were reviewed. Oxygen saturation in room air was
      screened by percutaneous pulse oximetry. HPS cases were compared with similar age
      non-HPS recipients (n = 38) to determine differences in clinical characteristics,
      Pediatric End-Stage Liver Disease (PELD) scores, and posttransplantation
      survival. Of 211 patients referred and 114 patients transplanted, 7 met criteria
      for HPS (3.3% and 6.1%, respectively). Patients with HPS had lower PELD score (
      0.4 +/- 5.9 vs. 11 +/- 11; P = 0.01) and total bilirubin (1.7 +/- 1.1 vs. 11.2 +/
      10.1; P = 0.02) at the time of transplantation. Four of 7 patients with HPS had
      polysplenia/interrupted inferior vena cava (PS/IVC) compared with 0 of 38 age
      matched controls (P = 0.0002). Three patients with HPS did not have cirrhosis; 2
      of these 3 had PS/IVC. All HPS cases normalized room air oxygen saturation by 6
      months, and survival after transplantation in HPS cases was 100%. Marked hepatic
      synthetic or biochemical dysfunction may not be present, and cirrhosis is not a
      requirement for the development of HPS in children. HPS in children is frequently
      associated with PS/IVC. Histologic evidence of abnormal intrahepatic portal vein
      flow and the demonstration of portosystemic communications at any level should be
      sought in children presenting with unexplained intrapulmonary vascular
      dilatation. Liver transplantation for HPS in childhood may be appropriate even in
      the absence of cirrhosis.

PMID- 17457898
TI  - PELD allocation and acute liver/graft failure.

PMID- 17457900
TI  - Increased susceptibility of human respiratory syncytial virus to neutralization
      by anti-fusion protein antibodies on adaptation to replication in cell culture.
AB  - Subgroup A respiratory syncytial viruses present in respiratory secretions and
      low passage level cell culture isolates were found to be markedly less
      susceptible to neutralization with monoclonal antibodies (MAbs) to the F
      glycoprotein than the cell culture adapted A2 virus strain. Low passage virus
      isolates collected over a 20 year period and belonging to several sub-group A
      lineages were refractory to neutralization with antibodies recognizing two major
      neutralizing antigenic sites located sub-terminally at opposite ends of the F(1)
      glycoprotein sub-unit. On further passage in cell culture, virus isolates
      exhibited both increased infectivity titers and increased susceptibility to
      neutralization by antibodies to both antigenic sites. The consensus nucleotide
      sequence of the membrane associated proteins M and of the SH, G and F
      glycoprotein genes, and their intergenic regions were compared for neutralization
      resistant and susceptible stocks of one virus strain, R17532. No changes were
      observed in the known monoclonal antibody epitopes on the F glycoprotein. In line
      with this, the increase in susceptibility was not found to be associated with any
      increased binding of monoclonal antibody to isolated F glycoprotein in a BIAcore
      assay, thus excluding the possibility that passage in cell culture selected for
      viruses with mutations in the antibody binding sites. M and SH genes were
      conserved but a number of sites in the G and F glycoprotein genes were found to
      vary on adaptation to cell culture suggesting that change in susceptibility to
      neutralization was associated with a change in the prevalent quasispecies present
      in the virus population. The genetic basis of phenotypic change in susceptibility
      remains to be determined.

PMID- 17457901
TI  - Isolation of therapeutic human monoclonal antibodies for varicella-zoster virus
      and the effect of light chains on the neutralizing activity.
AB  - Therapeutic antibodies against varicella-zoster virus (VZV) were isolated from a
      combinatorial library of human antibodies using a phage-display system. Purified
      gH:gL was used to screen the library, and approximately 300 clones were isolated.
      Eight kinds of Fab-cp3-fused molecules (clones 10, 24, 36, 60, 94, 120, 192, and
      431) neutralized viral infectivity. After conversion of Fab-cp3 antibodies to the
      Fab-protein A form, the concentrations of antibodies showing 50% inhibition of
      plaque formation ranged from 0.12 to 400 nM. Clones 10, 24, 94, 120 and 431
      neutralized wild strains without showing strain specificity and were further
      converted to human IgG(1). Two clones (24 and 94) were confirmed to react with
      gH:gL and VZV-infected cells. IgG of clone 94 prevented spreading of infected
      cells. Thus these antibodies exhibited the typical phenotype of anti-gH antibody.
      Next the contribution of light (L) chains to neutralizing activity was analyzed
      by comparing the effect of L chain of clones 10, 120, and 192 with the identical
      heavy chain on their neutralizing activity. The L chain in the Fab form of clone
      94 was replaced by L chains of clones 10, 24, 36, and 60 and the neutralizing
      activity of these replaced antibodies was weaker than that of the prototype clone
      94. When the kappa-L chain of clone 94 was replaced by the lambda-L chain of
      clone 24, this antibody possessed neutralizing activity despite the kappa-lambda
      class change. Thus, human antibody library against VZV-gH has been established
      and characterized the role of the L chain in VZV-neutralizing activity to
      engineering further an antibody with stronger neutralizing activity.

PMID- 17457902
TI  - Characterization of viral kinetics in patients with hepatitis B e antigen
      positive chronic hepatitis B.
AB  - A study was conducted during a 1 year follow-up to characterize the viral
      kinetics in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and to
      develop a model of predicting the probability of spontaneous HBeAg
      seroconversion. Fifty-seven patients with HBeAg-positive chronic hepatitis B were
      enrolled with monthly follow-ups from three Phase III clinical trial placebo
      groups. According to serial viral loads, 30 patients (52.6%) with the stationary
      pattern maintained stable HBV DNA levels with fluctuations of less than 1.5 log
      copies/ml. Twenty patients (35.1%) with the declining pattern exhibited a
      spontaneous decline of more than 1.5 log copies/ml without a following rebound of
      at least 1.5 log copies/ml. The remaining seven patients (12.3%) had the wavering
      pattern. Both declining and wavering patterns, when compared with the stationary
      pattern, had significantly higher hepatic necroinflammation in terms of ALT and
      Knodell scores at the baseline and peak ALT levels during the follow-up period.
      The declining pattern had a significantly better clinical outcome in terms of the
      lowest final HBV DNA and a reduction in the necroinflammatory score after 1 year.
      Furthermore, the declining pattern had a favorable HBeAg seroconversion rate
      (40%) compared with the wavering (14.3%) and stationary patterns (0%). A
      regression equation, incorporating simultaneous serum bilirubin, ALT, and HBV DNA
      levels, predicted the probability of HBeAg seroconversion with a sensitivity of
      76.8% and a specificity of 74.7%. In conclusion, different viral kinetic patterns
      in patients with chronic hepatitis B implicate distinct clinical significance and
      immunologic perspective.

PMID- 17457903
TI  - Hepatitis B virus genotypes in children and adolescents in Japan: before and
      after immunization for the prevention of mother to infant transmission of
      hepatitis B virus.
AB  - The genotype distribution of hepatitis B virus (HBV) was investigated in 118
      children in Japan. One hundred and sixteen children (98%) had chronic HBV
      infection, and the remainder had acute hepatitis. Genotyping of HBV was
      determined by PCR and sequencing analysis in the S gene. Genotype C (86%) was the
      most frequent, followed by genotype B (9%), D (2.5%), and A (1.0%). Transmission
      routes of HBV to children were from mothers in 91 patients (77%), fathers in 8
      (6.5%), mother or father in 1 (1%), family members other than the parents in 5
      (4%), and unknown in 13 (11.5%). The relationship between routes of HBV
      transmission and HBV genotypes was studied. Eighty-eight (97%) of 91 children of
      mother-to-infant transmission were genotype C, while 13 (49%) of 27 children of
      the routes other than the mother to infant transmission were genotype C. The
      number of children with genotype C who were infected from their mothers was
      significantly higher than those with genotype B, D, or A (P < 0.01). In
      conclusion, HBV genotypes influence not only clinical characteristics but also
      the mechanisms of inter-personal HBV transmission.

PMID- 17457904
TI  - A putative new domain target for anti-hepatitis B virus: residues flanking
      hepatitis B virus reverse transcriptase residue 306 (rtP306).
AB  - Previous work showed that conservation of proline at residue 306 (rtP306) of
      hepatitis B virus (HBV) reverse transcriptase (RT) is crucial for virus
      replication and encapsidation of pregenomic RNA (pgRNA). In this study, the
      functions of residues flanking rtP306 in HBV RT (rtG304, rtY305, rtA307, rtL308
      and rtL311) are presented. Alanine or phenylalanine was used to substitute these
      residues by constructing site-directed mutants which were used to transfect Huh-7
      cells. Replication competencies and encapsidation efficiencies were compared
      between the mutants and the parental viral strain. Substitutions at these
      residues resulted in marked decrease of replication competency, which was
      confirmed by Southern blot hybridization of HBV DNA isolated from
      intracytoplasmic core particles, and trans-complementation between a non
      replicative defective mutant and corresponding RT mutants. Impaired pgRNA
      encapsidation efficiency of these mutants was shown as the major mechanism for
      decreased replication efficiency. Since residues from rt304 to rt311 are highly
      conserved among genotypes A-H HBV strains, results suggest that rt304 to rt311 in
      HBV RT may serve as a putative anti-HBV new target domain.

PMID- 17457905
TI  - Viral load and genomic integration of HPV 16 in cervical samples from HIV-1
      infected and uninfected women in Burkina Faso.
AB  - The relationships between human papillomavirus type 16 (HPV 16) viral load, HPV
      16 integration status, human immunodeficiency virus type 1 (HIV-1) status, and
      cervical cytology were studied among women enrolled in a cohort of female sex
      workers in Burkina Faso. The study focused on 24 HPV 16-infected women. The HPV
      16 viral load in cervical samples was determined by real-time PCR. Integration
      ratio was estimated as the ratio between E2 and E6 genes DNA copy numbers.
      Integrated HPV16 viral load was defined as the product of HPV 16 viral load by
      the integration ratio. High HPV 16 viral load and high integration ratio were
      more frequent among women with squamous intraepithelial lesions compared with
      women with normal cytology (33% vs. 11%, and 33% vs. 0%, respectively), and among
      women with high-grade squamous intraepithelial lesions compared with women
      without high-grade squamous intraepithelial lesions (50% vs. 17%, and 50% vs.
      11%, respectively). High HPV 16 DNA load, but not high integration ratio, was
      also more frequent among HIV-1-positive women (39% vs. 9%; and 23% vs. 18%,
      respectively). The absence of statistical significance of these differences might
      be explained by the small study sample size. High-integrated HPV 16 DNA load was
      significantly associated with the presence of high-grade squamous intraepithelial
      lesions (50% vs. 5%, P = 0.03) in univariate and multivariate analysis (adjusted
      odds-ratio: 19.05; 95% confidence interval (CI), 1.11-328.3, P = 0.03), but not
      with HIV-1 or other high-risk HPV types (HR-HPV). Integrated HPV 16 DNA load may
      be considered as a useful marker of high-grade cervical lesions in HPV 16
      infected women.

PMID- 17457906
TI  - Temporal dynamics of human T-lymphotropic virus type I tax mRNA and proviral DNA
      load in peripheral blood mononuclear cells of human T-lymphotropic virus type I
      associated myelopathy patients.
AB  - Human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of HTLV-I
      associated myelopathy/tropical spastic paraparesis (HAM/TSP). High HTLV-I
      provirus load and tax mRNA level have been suggested as predictors of disease
      progression in patients with HAM/TSP, but little is known about the temporal
      variation in patients. To clarify the role of high proviral and tax mRNA loads
      and their fluctuations in the pathogenesis of HAM/TSP, we measured proviral load
      and tax mRNA in serially collected peripheral blood mononuclear cells (PBMCs)
      from nine patients with HAM/TSP during a long-term follow-up, by use of real-time
      polymerase chain reaction using tax primers. The real-time PCR quantitation
      revealed a wide range of variation of proviral loads (7.82-97.13 copies per 100
      PBMCs) and tax mRNA (0.20-245.30 copies) among HAM/TSP patients. Patients showed
      three different patterns of HTLV-I tax mRNA loads during the course of the
      disease. Tax mRNA load showed a separate evolution with respect to the disease.
      The dynamic patterns of proviral load and mRNA Tax expression suggest that only
      the permanent presence of a basal level of tax mRNA, rather than the tax mRNA
      load, is related to the development of HAM/TSP. To our knowledge, this is the
      first longitudinal study to determine tax mRNA expression at different clinical
      stages.

PMID- 17457907
TI  - Molecular characterization of rare G3P[9] rotavirus strains isolated from
      children hospitalized with acute gastroenteritis.
AB  - In 2004, an epidemiological survey of human rotavirus infection in Chiang Mai,
      Thailand detected two uncommon human rotavirus strains (CMH120/04 and CMH134/04)
      bearing AU-1-like G3P[9] genotypes in 1 year old children hospitalized with acute
      gastroenteritis. The CMH120/04 and CMH134/04 rotavirus strains were characterized
      by molecular analyses of their VP6, VP7, VP8*, and NSP4 gene segments as well as
      the determination of RNA patterns by polyacrylamide gel electrophoresis (PAGE).
      Analysis of the VP8* gene revealed a high level of amino acid sequence identities
      with those of P[9] rotavirus reference strains, ranging from 94.9% to 98.3%. The
      highest identities were shared with the human rotavirus AU-1 strain at 97.8% and
      98.3% for CMH120/04 and CMH134/04 strains, respectively. Analysis of the VP7 gene
      sequence revealed the highest identities with G3 human rotavirus strain KC814 at
      96.6% and 96.2% for CMH120/04 and CMH134/04 strains, respectively. Based on the
      analyses of VP7 and VP8* genes, CMH120/04 and CMH134/04 belonged to G3P[9]
      genotypes. In addition, analyses of VP6 and NSP4 sequences revealed a VP6
      subgroup (SG) I, with NSP4 genetic group C specificities. Moreover, both strains
      displayed a long RNA electrophoretic pattern. The finding of uncommon G3P[9]
      rotaviruses in pediatric patients provided additional evidence of the
      genetic/antigenic diversities of human group A rotaviruses in the Chiang Mai area
      of Thailand.

PMID- 17457908
TI  - Human papillomavirus genotypes associated with cervical cytologic abnormalities
      and HIV infection in Ugandan women.
AB  - Human papillomavirus (HPV) infection is associated with almost all cases of
      cervical cancer, and cervical cancer is a common malignancy in women living in
      developing countries. A cross-sectional study was conducted to determine the
      prevalence of HPV infection, human immunodeficiency virus (HIV) infection, and
      cervical cytologic abnormalities in women presenting to a sexually transmitted
      infections clinic in Kampala, Uganda. In June and July, 2002, 135 women underwent
      complete physical exams including Papanicolaou (Pap) smears. HIV status was
      evaluated by serology. Cervical and vaginal swabs were obtained by clinicians and
      tested for HPV genotypes by PCR/reverse blot strip assay. Of the 106 women with
      cervical swabs adequate for HPV testing, the HPV prevalence was 46.2% (49/106).
      HIV prevalence was 34.9% (37/106). High risk genotypes 52, 58, and 16 were the
      genotypes detected most commonly. Eighteen percent (9/49) of women infected with
      HPV were found to have genotypes 16 and/or 18. Seventy-three percent (27/37) of
      HIV-positive women versus 16% (10/63) of HIV-negative women had abnormal Pap
      smears (P < 0.0001). Among HIV-positive women, abnormal Pap smears were
      associated with the presence of high risk HPV genotypes (P < 0.001). The majority
      of women infected with HPV attending this sexually transmitted infections clinic
      in Uganda were infected with high risk HPV genotypes other than 16 and 18. Future
      studies should focus on whether current HPV vaccine formulations, that are
      limited to high risk genotypes 16 and 18, would be effective at decreasing the
      burden of cervical cancer in this population.

PMID- 17457909
TI  - Prevalence of the most common high-risk HPV genotypes among women in three new
      independent states of the former Soviet Union.
AB  - Type distribution of HPV has been studied in different geographic regions, but
      the data are scanty from the new independent states of the former Soviet Union.
      Here the HPV prevalence and distribution of the most frequent high-risk HPV types
      among 3,187 women at different risk for HPV and cervical intraepithelial
      neoplasia in Russia, Belarus, and Latvia is reported. HPV detection, type
      distribution and viral load analysis in DNA samples from cervical scrapes were
      done with real-time PCR-based assay detecting HPV types 16, 18, 31, 33, 35, 39,
      45, 52, and 58. The overall HPV prevalence was 31.2%, HPV16 was the most
      prevalent type followed by HPV31 and HPV33 group. The overall HPV prevalences in
      Russia, Belarus and Latvia were 33.4%, 27.5%, and 26.2%. The type distributions
      were similar in these countries, except for Latvia where HPV39 was the third
      prevalent genotype. HPV prevalence was highest (40.8%) among women from sexually
      transmitted disease clinic, followed by 30.9% among gynecological outpatients and
      27.2% in screening patients. HPV detection increased with cytological abnormality
      (P = 0.0001) and lesion grade in the biopsy (P = 0.0001), from 27% to 72% in
      normal samples to cancer, and from 64% to 77% in cervical intraepithelial
      neoplasia 1 to cancer. The normalized viral loads varied greatly between and
      among different HPV-types. The mean log HPV33 group copies/cell increased from
      negative for intraepithelial lesions to cancer (P = 0.049). Distribution of the
      most common high-risk HPV-types seems to be similar in these countries as
      reported in other major geographical regions.

PMID- 17457910
TI  - Molecular epidemiology of hepatitis A in St. Petersburg, Russia, 1997-2003.
AB  - The molecular epidemiology of hepatitis A virus (HAV) strains circulating in the
      St. Petersburg and Karelia regions was studied during 1997-2003. Hepatitis A
      virus RNA was isolated from both clinical samples (stools or sera) and
      environmental samples (sewage water). RT-PCR was carried out using different
      primer pairs from the VP1/2A and VP1 genomic regions, the variable parts of the
      HAV genome. PCR products were sequenced and 306 nucleotides from the VP1/2A and
      332 nucleotides from the VP1 region were used for phylogenetic analysis. The
      results show that the IA subtype was the most common during the follow-up period:
      >90% of the isolated HAV strains belonged to that subtype. The HAV strains found
      in intravenous drug users belonged to subtypes IA and IIIA. Only one out of a
      total of 88 sequenced strains was of the IB subtype. The subtypes IB and IIIA
      were found only in 2001-2003, which suggests that new strains were introduced
      into the endemic situation. The results indicate the usefulness of molecular
      epidemiological methods in studying changes in the circulating HAV strains and in
      tracing transmission routes.

PMID- 17457911
TI  - Hepatitis C recurrence and fibrosis progression are not increased after living
      donor liver transplantation: a single-center study of 289 patients.
AB  - Today, hepatitis C virus (HCV) is the leading cause for liver transplantation
      (LT) and viral recurrence is almost universal. It has been suggested that viral
      replication within the transplanted tissue might be increased in organs of
      reduced size such as LD grafts. In the current literature the data is
      controversial, with many studies lacking routine liver biopsies. We performed a
      retrospective analysis of 289 HCV-LT (20 LD splits) patients receiving
      transplants between 1997 and 2005. Patient and organ survival, intensity of HCV
      recurrence, and fibrosis progression were analyzed with respect to deceased donor
      (DD) LT (DDLT) or living donor (LD) LT (LDLT). Organ and patient survival was
      significantly better for full-size recipients than for split-liver patients, with
      P = 0.037 for organ survival and P = 0.037 for patient survival; yet there were
      no significant differences when split-liver patients with large hepatocellular
      carcinoma (HCC) beyond the Milan criteria (n = 3) were excluded from the analysis
      (P > 0.05). First year fibrosis progression was 1.29 in full-size grafts and 1.07
      in split-livers (P = not significant). In conclusion, in our patient sample,
      intensity of HCV recurrence was not increased in LD graft recipients compared to
      full-size recipients. Patient and organ survival were similar when patients with
      large HCC and early tumor recurrence were excluded from analysis. LDLT can
      therefore be advocated for HCV patients.

PMID- 17457912
TI  - Occult hepatitis B virus infection in the setting of hepatitis C virus (HCV) and
      human immunodeficiency virus (HIV) co-infection: clinically relevant or a
      diagnostic problem?
AB  - The clinical relevance of occult hepatitis B virus (HBV) infection, defined as
      detectable HBV DNA serum/liver, in the absence of hepatitis B surface antigen
      (HBsAg), is unclear. We determined the prevalence of serum occult HBV infection
      in HIV/HCV co-infected patients enrolled in APRICOT, a randomized multinational
      trial that investigated the efficacy and safety of peginterferon alfa-2a (40 kDa)
      plus ribavirin for treatment of HCV. We also examined the effect of prior HBV
      exposure to liver histology at baseline. Only HBsAg-negative patients were
      eligible. At screening, serum HBV DNA was assessed by commercial assay (detection
      limit = 200 copies/mL). Patients were divided into four serological groups: anti
      HBs+/anti-HBc+; anti-HBs-/anti-HBc+; anti-HBs+/ anti-HBc-; anti-HBs-/anti-HBc-.
      Baseline liver biopsy grade and stage were compared among groups. Serum HBV DNA
      was undetectable in all patients, (n = 866). Results of anti-HBs and anti-HBc was
      available for 176 patients: 60 (34.1%) anti-HBs+/anti-HBc+; 60 (34.1%) anti-HBs
      /anti-HBc+; 11 (6.3%) anti-HBs+/anti-HBc-; 45 (25.6%) anti-HBs-/anti-HBc-. There
      were no differences among the groups in the histological grade or stage at
      baseline liver biopsies. Occult HBV infection in serum was not detected in this
      large immunocompetent cohort. Moreover, prior exposure to HBV did not appear to
      have any affect on baseline liver histology.

PMID- 17457913
TI  - Transplacental infection of Coxsackievirus B3 pathological findings in the fetus.
AB  - Coxsackievirus intrauterine infection has been documented mostly on the basis of
      indirect evidence of transplacental transmission, with neonatal manifestations
      ranging from asymptomatic infection to meningoencephalitis, myocarditis, and
      generalized sepsis. This is the first report of prenatal findings and
      fetoplacental pathology in a third trimester fetus with coxsackie B3
      transplacental infection confirmed by molecular techniques. Prenatal ultrasound
      detected severe reduction of fetal movements at the 27th week. Late onset fetal
      akinesia deformation sequence with mild arthrogryposis, necrotic
      meningoencephalitis with vascular calcifications, interstitial pneumonitis, mild
      myocardial hypertrophy, and chronic monocytic placental villitis were the
      cardinal findings at fetal autopsy following interruption of the pregnancy.

PMID- 17457914
TI  - Molecular and phylogenetic analysis of human influenza virus among Iranian
      patients in Shiraz, Iran.
AB  - Influenza is a viral respiratory pathogen responsible for frequent seasonal
      epidemics. There are currently three major human influenza viruses in global
      circulation namely A/H1N1, A/H3N2, and B. The objective of this study was to
      determine the human influenza virus genotypes in Shiraz, the capital of the Fars
      province of Iran. Three hundred patients suspected with human influenza virus
      infection were enrolled in this survey (2004-2005). The throat samples were
      cultured and titrated by hemagglutination (HA) assay. Typing and subtyping were
      performed by an in-house developed multiplex RT-PCR. Moreover, the phylogenetic
      analysis was carried out for HA gene. A total of 24 samples were found to be
      positive for human influenza virus infection, 17 H1N1 and 7 H3N2. These results
      were in agreement with the HI assay. The phylogenetic analysis results revealed
      that the Iranian H1N1 isolated were close to the A/New Caledonia/20/99 vaccine
      strain genetically and the Iranian H3N2 isolates were also related closely to the
      Fujian/411/021 and California/7/2004 vaccine strains. However, a slight genetic
      drift was found in these isolates. In conclusion, it was demonstrated that both
      influenza A subtypes A/H1N1 and A/H3N2 were dominant among Iranian patients in
      Shiraz during the 2004/5 winter season.

PMID- 17457915
TI  - Genetic variability of the fusion protein and circulation patterns of genotypes
      of the respiratory syncytial virus.
AB  - Although antigenic and genetic variations were shown to occur both in the G and F
      protein of respiratory syncytial virus (RSV), few studies looked at the variation
      of F gene. The F genotypes were determined by the evaluation of clustering
      patterns, via the phylogenetic analysis of the nucleotide sequences of a variable
      region in the F gene. One hundred seventy-nine strains obtained from a children's
      hospital in Korea over nine consecutive epidemics were included. The relationship
      between the F and G genotypes was analyzed with the G genotypes previously
      published by the authors. The phylogenetic analysis of the variable region from
      the F gene revealed 9 genotypes among 129 group A RSVs and 4 genotypes among 50
      group B RSVs. In each of the epidemics, the dominant genotypes were replaced with
      new genotypes in consecutive epidemics. In each of the epidemics of group B RSVs,
      the predominant genotype alternated between genotypes. Most of the strains which
      clustered to a particular F genotype were assigned to particular G genotype(s).
      By determining the nearly entire sequences of the F genes, we revealed the
      percentage of the nucleotide differences which resulted in amino acid coding
      changes was determined to be much great in two distinct variable regions of the F
      gene. Our results indicated that the F gene of the RSVs may be continuously
      evolving under selective pressure in a distinct pattern, and that the genetic
      variability of the F protein is associated with that of the G protein.

PMID- 17457916
TI  - Serum levels of anti-NS4a and anti-NS5a predict treatment response of patients
      with chronic hepatitis C.
AB  - In order to understand better the clinical significance and prognostic value of
      antibody responses to HCV proteins and in search for parameters that may allow
      the early identification of non-sustained responders to therapy, antibody levels
      were measured against NS3, NS4a and NS5a at baseline in the serum of 120 patients
      chronically infected with HCV of genotype 1 that were classified as sustained
      responders, relapsers, or non-responders to therapy. The capacity of these
      antibody tests to predict therapy-outcome was evaluated. While no differences
      were observed in the anti-NS3 responses in these different response groups, anti
      NS4a and anti-NS5a antibodies were observed more frequently and at higher titres
      in sustained responders versus non-responders or non-sustained responders (=non
      responders + relapsers). Based on this observation, a combination of test results
      consisting of 'the absence of NS4a (AA 1687-1718) antibody at baseline and the
      presence of HCV-RNA exceeding 10(5) IU/ml after 1 week of treatment' was
      identified which predicts non-sustained response to treatment with 100%
      certainty. Replacing the HCV-RNA decision limit by a HCV-core antigen level of
      >15 pg/ml resulted in the same predictive value. The proposed algorithm also
      holds for patients treated with peg-interferon and ribavirin. In conclusion, in
      patients with chronic HCV infection, the decision to continue or stop treatment
      can be made after 1 week of treatment with (peg)-interferon alpha and ribavirin.

PMID- 17457917
TI  - Outbreak of acute hemorrhagic conjunctivitis in Maharashtra and Gujarat states of
      India, caused by Coxsackie virus A-24 variant.
AB  - Acute hemorrhagic conjunctivitis is associated with enteroviruses. Among these,
      Coxsackie A-24 variant (CA-24) and Enterovirus-70 (EV-70) are known to cause
      epidemics and pandemics. An outbreak of acute hemorrhagic conjunctivitis occurred
      in August-September 2003 in Maharashtra and Gujarat states of India. The present
      investigation was carried out to determine the viral etiological agent associated
      with the epidemic. Virus isolates were obtained from 11 eye swabs of
      conjunctivitis patients using HeLa/ Hep-2 cell lines. The isolates were
      characterized by serological and mouse pathogenecity tests, RT-PCR using
      enterovirus common primers (VP4-VP2), CA-24 specific primers (3C-proteinase
      region), EV-70 primers (VP-3) followed by sequencing, and phylogenetic analysis.
      The virus was characterized as a Coxsackie A-24 variant (CA-24v) and none of the
      isolates were found to be positive for EV-70. Sequencing of the PCR products
      derived from all the 11 isolates revealed 98.4% (SE 0.20) nucleotide identity
      within the Indian strains and 98.6% (0.50) and 94.4% (0.30) nucleotide identity
      respectively with the West Indies and Asian strains reported worldwide. The
      findings suggest that the outbreak of acute hemorrhagic conjunctivitis that
      occurred in Maharashtra and Gujarat states of India during August-September 2003
      was caused by the Coxsackie A-24 variant (CA-24v).

PMID- 17457918
TI  - The roles of CD81 and glycosaminoglycans in the adsorption and uptake of
      infectious HCV particles.
AB  - Because appropriate cell-culture systems or small-animal models have been
      lacking, the early steps in the HCV life cycle have been difficult to study. A
      cell culture system was developed recently that allows production of infectious
      HCV. In this study, infectious HCV particles produced in cultured cells were
      used. To clarify the role of CD81 in HCV attachment and entry, the effect of anti
      CD81 antibody was examined. The antibody blocked HCV virion entry but not
      particle attachment. Only the fraction bound to a heparin affinity column and
      eluted with 0.3 M NaCl productively infected Huh7 cells, indicating that
      infectious HCV particles bind to heparin. Both heparin treatment of the virus
      particles and heparinase treatment of the Huh7 cells reduced virus-cell binding
      without substantially inhibiting HCV infectivity. Finally, to confirm the role of
      both heparin sulfate proteoglycan (HSPG) and CD81 in HCV entry, the effects of
      heparinase I and anti-CD81 antibody were analyzed. No productive RNA replication
      was detected in the Huh7 cells in the presence of both heparinase I and anti-CD81
      antibody. In conclusion, these data suggested that both HSPG and CD81 are
      important for HCV entry. HSPG may play a role in the initial cell surface binding
      of infectious HCV particles and CD81 is conceivably correlated with HCV entry
      after viral attachment.

PMID- 17457919
TI  - Prophylactic effects of chitin microparticles on highly pathogenic H5N1 influenza
      virus.
AB  - Highly pathogenic avian influenza virus (H5N1) is an emerging pathogen with the
      potential to cause great harm to humans, and there is concern about the potential
      for a new influenza pandemic. This virus is resistant to the antiviral effects of
      interferons and tumor necrosis factor-alpha. However, the mechanism of interferon
      independent protective innate immunity is not well understood. The prophylactic
      effects of chitin microparticles as a stimulator of innate mucosal immunity
      against a recently obtained strain of H5N1 influenza virus infection were
      examined in mice. Clinical parameters and the survival rate of mice treated by
      intranasal application of chitin microparticles were significantly improved
      compared to non-treated mice after a lethal influenza virus challenge. Flow
      cytometric analysis revealed that the number of natural killer cells that
      expressed tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and
      that had migrated into the cervical lymph node was markedly increased (26-fold)
      after intranasal treatment with chitin microparticles. In addition, the level of
      IL-6 and interferon-gamma-inducible protein-10 (IP-10) in the nasal mucosa after
      H5N1 influenza virus challenge was decreased by prophylactic treatment with
      chitin microparticles. These results suggest that prophylactic intranasal
      administration of chitin microparticles enhanced the local accumulation of
      natural killer cells and suppressed hyper-induction of cytokines, resulting in an
      innate immune response to prevent pathogenesis of H5N1 influenza virus.

PMID- 17457921
TI  - Antiretroviral drug resistance and phylogenetic diversity of HIV-1 in Chile.
AB  - This study reports the analysis of human immunodeficiency virus type 1 (HIV-1)
      protease (PR) and reverse transcriptase (RT) coding sequences from 136 HIV-1
      infected subjects from Chile, 66 (49%) of them under antiretroviral (ARV)
      treatment. The prevalence of mutations conferring high or intermediate resistance
      levels to ARVs was 77% among treated patients and 2.5% among drug-naive subjects.
      The distribution of resistance prevalence in treated patients by drug class was
      61% to nucleoside RT inhibitors, 84% to nonnucleoside RT inhibitors, and 46% to
      PR inhibitors. Phylogenetic analysis revealed that 115 (85%) subjects were
      infected with subtype B viruses, 1 with a subtype F1 virus, and 20 (15%) carried
      BF intersubtype recombinants. Most BF recombinants grouped into two clusters, one
      related to CRF12_BF, while the other could represent a new circulating
      recombinant form (CRF). In conclusion, this is the first report analysing the
      prevalence of ARV resistance which includes patients under HAART from Chile.
      Additionally, phylogenetic analysis of the PR-RT coding sequences reveals the
      presence of BF intersubtype recombinants.

PMID- 17457922
TI  - Analysis of the complete hepatitis B virus genome in patients with genotype C
      chronic hepatitis in relation to HBeAg and anti-HBe.
AB  - To investigate the relationship between viral factors and the development of
      chronic hepatitis B, the entire hepatitis B virus (HBV) genome of chronic
      carriers at different disease stages were analyzed. Eighty genotype C HBV
      carriers including 12 hepatitis B e antigen (HBeAg) positive asymptomatic
      carriers (Group A), 49 HBeAg positive patients with chronic liver diseases (Group
      B) and 19 anti-HBe positive patients with chronic liver diseases (Group C) were
      studied. HBV nucleic acid from serum samples was sequenced directly and compared
      with GenBank reference sequences HBV X01587 and M12906. On phylogenetic analysis,
      76 cases were genotype C2. Of the 76 genotype C2 cases, the nucleotide and amino
      acid substitution rates in the precore/core region were significantly higher in
      Groups B and C than in Group A, also in Group C than in Group B. The nucleotide
      substitution rates in the full genome and the core promoter region were
      significantly higher in Group C than in Group A, also in group C than in Group B.
      The nucleotide and amino acid substitution rates in the X region were
      significantly higher in Group C than in Group A. The amino acid substitution rate
      in the pre-S2 region was significantly higher in Group C than in Group B.
      Deletion mutations were found mainly in Groups B and C. This whole genome
      analysis of HBV chronic carriers suggested that the nucleotide substitutions and
      deletions in HBV were closely associated with the pathogenesis of chronic HBV
      infection.

PMID- 17457923
TI  - Detection of human rotavirus G9P[8] strains circulating in Argentina:
      phylogenetic analysis of VP7 and NSP4 genes.
AB  - During the surveillance of rotavirus strains that were circulating in Argentinean
      children from 2000 to 2004, seven rotaviruses were detected bearing the genotype
      combination G9P[8]. The molecular characterization of the VP7 and NSP4 genes and
      the RNA migration patterns support the hypothesis that rotaviruses G9 could have
      been reintroduced into Argentina as a novel G9P[8] strain, rather than represent
      VP7 gene reassortants from G9P[6] strains that had been circulating previously in
      this country.

PMID- 17457924
TI  - Ongoing subclinical infection of hepatitis E virus among blood donors with an
      elevated alanine aminotransferase level in Japan.
AB  - Ongoing subclinical infection of hepatitis E virus (HEV) has not been fully
      studied. In the present study, serum samples were collected from 6700 voluntary
      blood donors with an elevated alanine aminotransferase (ALT) level of 61-476 IU/l
      at a Japanese Red Cross Blood Center, and were tested for the presence of IgG,
      IgM and IgA classes of antibodies to HEV (anti-HEV) by in-house ELISA and HEV RNA
      by nested RT-PCR. Overall, 479 blood donors (7.1%) were positive for anti-HEV
      IgG, including 8 donors with anti-HEV IgM and 7 donors with anti-HEV IgA. Among
      the nine donors with anti-HEV IgM and/or anti-HEV IgA, six had detectable HEV
      RNA. The presence of HEV RNA was further tested in 10-sample minipools of sera
      from the remaining 6691 donors, and three donors including one without anti-HEV
      IgG were found to be positive for HEV RNA. When stratified by ALT level, the
      prevalence of HEV RNA was significantly higher among the 109 donors with ALT > or
      = 201 IU/l than among the 6591 donors with ALT of 61-200 IU/l (2.8% vs. 0.1%, P <
      0.0001). The HEV isolates obtained from the nine viremic donors segregated into
      genotype 3, shared a wide range of identities of 85.6-98.5% and were 87.3-93.9%
      similar to the Japan-indigenous HEV strain (JRA1), in the 412-nucleotide sequence
      of open reading frame 2. This study suggests that approximately 3% of Japanese
      individuals with ALT > or = 201 IU/l have ongoing subclinical infection with
      various HEV strains.

PMID- 17457925
TI  - Mother-to-infant transmission of multiple blood-borne viral infections from multi
      infected mothers.
AB  - Infants born from mothers with multiple blood-borne viral infections are at risk
      of multiple transmissions. Whether the risk of transmission of multiple
      infections increases with the number of viruses infecting the mother is still
      unknown. The aim of this study was to describe the risk of mother-to-infant
      transmission of multiple infections from multi-infected mothers. Sixty-four
      pregnant women infected by at least two viruses among human immunodeficiency
      virus-type 1 (HIV-1), hepatitis C virus, TT virus, and GB virus type C, together
      with their 64 infants, were studied. Maternal blood samples were collected in the
      third trimester of pregnancy and all infants were prospectively followed for
      evaluation of transmission within 3 months after birth and two times in the
      subsequent 24 months. Transmission of single and of dual infection from mothers
      infected by two viruses was, respectively, 10/40 (25%) and 5/40 (12.5%) and from
      mothers infected by three viruses 9/20 (45%) and 2/20 (10%). One (25%) infant
      infected by one virus was born from the four mothers infected by four viruses.
      Transmission of single or dual infection was not significantly associated with
      the number of viruses infecting the mother (P = 0.9) in the linear regression
      analysis. Present study suggests the absence of a synergistic effect from viral
      interactions toward mother-to-infant transmission of multiple infections and
      supports the hypothesis that transmission from multi-infected mothers is the
      result of the specific interaction between each virus and the host. These
      observations may be of clinical relevance in perinatal counseling.

PMID- 17457926
TI  - Microarray assay for evaluation of the genetic stability of modified vaccinia
      virus Ankara B5R gene.
AB  - Adverse events associated with the use of live smallpox vaccines have led to the
      development of a new generation of attenuated smallpox vaccines that are prepared
      in cultured cells as alternatives. The inability to conduct direct clinical
      evaluation of their efficacy in humans demands that licensure be based on animal
      studies and exhaustive evaluation of their in vitro properties. One of the most
      important characteristics of live viral vaccines is their genetic stability,
      including reversion of the vaccine strain to more virulent forms, recombination
      with other viral sequences to produce potentially pathogenic viruses, and genetic
      drift that can result in decrease of immunogenicity and efficacy. To study
      genetic stability of an immunoessential vaccinia virus gene in a new generation
      smallpox vaccine, an advanced oligonucleotide microchip was developed and used to
      assay for mutations that could emerge in B5R gene, a vaccinia virus gene encoding
      for a protein that contains very important neutralizing epitopes. This microarray
      contained overlapping oligonucleotides covering the B5R gene of modified vaccinia
      virus Ankara (MVA), a well-studied candidate smallpox vaccine. The microarray
      assay was shown to be able to detect even a single point mutation, and to
      differentiate between vaccinia strains. At the same time, it could detect newly
      emerged mutations in clones of vaccinia strains. In the work described here, it
      was shown that MVA B5R gene was stable after 34 passages in Vero and MRC-5 cells
      that were proposed for use as cell substrates for vaccine manufacture.
      Potentially, the proposed method could be used as an identity test and could be
      extended for the entire viral genome and used to monitor consistency of vaccine
      production.

PMID- 17457927
TI  - CNS midline cells influence the division and survival of lateral glia in the
      Drosophila nervous system.
AB  - Central nervous system (CNS) midline cells are essential for identity
      determination and differentiation of neurons in the Drosophila nervous system. It
      is not clear, however, whether CNS midline cells are also involved in the
      development of lateral glial cells. The roles of CNS midline cells in lateral
      glia development were elucidated using general markers for lateral glia, such as
      glial cell missing and reverse polarity, and specific enhancer trap lines
      labeling the longitudinal, A, B, medial cell body, peripheral, and exit glia. We
      found that CNS midline cells were necessary for the proper expression of glial
      cell missing, reverse polarity, and other lateral glia markers only during the
      later stages of development, suggesting that they are not required for initial
      identity determination. Instead, CNS midline cells appear to be necessary for
      proper division and survival of lateral glia. CNS midline cells were also
      required for proper positioning of three exit glia at the junction of segmental
      and intersegmental nerves, as well as some peripheral glia along motor and
      sensory axon pathways. This study demonstrated that CNS midline cells are
      extrinsically required for the proper division, migration, and survival of
      various classes of lateral glia from the ventral neuroectoderm.

PMID- 17457928
TI  - Stereological evaluation of liver volume in living donor liver transplantation
      using MDCT via the Cavalieri method.
AB  - In living donor liver transplantation (LDLT), obtaining the precise volume of the
      graft is very important to decrease volume-related postoperative complications,
      especially in cases with suspected small-for size grafts. We used stereology
      based on the Cavalieri method (CM), a new method to measure liver graft volume,
      and compared the results with those obtained through intraoperative measurement
      (IOM) and through multidetector computed tomography (MDCT) measurement. Liver
      volumes estimated using the 3 methods were well-correlated with each other (r(2)
      = 0.94 and P < 0.001 for IOM and CM; r(2) = 0.91 and P < 0.001 for IOM and MDCT,
      and r(2) = 0.95 and P < 0.001 for CM and MDCT); however, they were different from
      each other (in descending order, 908 +/- 124 cm(2), 861 +/- 121 cm(2), and 777 +/
      168 cm(2) for MDCT, CM, and IOM, respectively). Although MDCT and CM
      overestimated the volumes, the results of CM were almost similar to those
      obtained via IOM. In conclusion, our results suggest that CM measured the liver
      graft volume more reliably. Thus, its use, particularly in cases with suspected
      small-for-size graft, may prove useful.

PMID- 17457929
TI  - HPRT minigene generates chimeric transcripts as a by-product of gene targeting.
AB  - The HPRT minigene is a selection cassette used for gene targeting in mouse
      embryonic stem (ES) cells and, it is unique since selection may be applied for
      its presence and absence. This minigene has two exon clusters separated by a
      small intron and splicing sequences. We find these exon clusters splice into
      exons from the target gene forming two different classes of chimeric transcripts.
      The first class is expressed by the endogenous promoter and includes upstream
      target gene exons spliced into minigene exons 3-8. The second class is expressed
      by the minigene's PGK promoter and includes minigene exons 1-2 spliced into
      downstream target gene exons. These chimeric transcripts may produce chimeric
      proteins that could influence phenotype. Therefore, we have designed two floxed
      HPRT minigenes that permit removal of either the 5' half of the minigene or the
      entire minigene via Cre-mediated recombination.

PMID- 17457930
TI  - Liver transplantation for status 1: the consequences of good intentions.
AB  - Status 1 is the listing category reserved for patients awaiting liver
      transplantation who are at risk of imminent death. This high allocation priority
      was intended to benefit patients with acute liver failure and children with
      severe chronic liver failure. However, the status 1 criteria were not well
      defined. The aims of this study, which used the Organ Procurement and
      Transplantation Network/Scientific Registry of Transplant Recipients database for
      patients wait-listed between February 27, 2002, and September 30, 2003, were to
      determine the indication and numbers of children and adults at status 1
      (including regional variations); examine death rates on the waiting list for
      children at vs. not at status 1; and examine time to death, transplant, or
      removal from the waiting list for both pediatric and adult status 1 candidates.
      During the study period, 40.3% of children and 6.1% of adults were transplanted
      at status 1. The indication was acute liver failure in 52.1% of adults and 31% of
      children. Among status 1 transplants, Regional Review Board exceptions were
      granted for 16.7% of children and 10.1% of adults. Death rates for children
      listed at status 1 by exception per patient-year at risk were substantially lower
      (0.51) than those of children with acute liver failure (4.06) or with chronic
      liver disease and Pediatric End-Stage Liver Disease score > or =25 (4.63). The
      percentage of adults who died while on the waiting list within 90 days of listing
      was more than twice that of children, whereas the percentages transplanted were
      similar. Patients listed and transplanted at status 1 were a heterogeneous
      population with an overrepresentation of children with varying degrees of chronic
      liver disease and other exceptions, and an associated wide variation in waiting
      list mortality. Recent changes in status 1 criteria provide stricter definitions,
      particularly for children, including the removal of the "by exception" category,
      with the intent that all candidates listed at status 1 share a similar mortality
      risk.

PMID- 17457931
TI  - Characterization of astrocyte-specific conditional knockouts.
AB  - Conditional gene knockouts are a very powerful tool for elucidating gene function
      in animal physiology and behavior. To obtain cell-specific knockouts, a promoter
      is utilized that drives expression of Cre recombinase specifically to the cell
      population of interest. We describe several transgenic lines of mice that were
      created in an attempt to obtain astrocyte-specific gene recombination. A 2 kb
      fragment from the human glial fibrillary acidic protein promoter is utilized to
      drive expression of inducible Cre recombinase, with both the Tet-Off and
      tamoxifen responsive systems. We show data obtained from crosses with two Cre
      reporter lines, ROSA26R and an astrocyte Cre reporter created in our laboratory,
      to assess the cell specificity of gene recombination. Additionally, our system is
      shown to successfully recombine a floxed Connexin43 locus, although recombination
      is not as extensive as seen in crosses with reporter lines.

PMID- 17457932
TI  - Nonanastomotic biliary strictures after liver transplantation, part 1:
      Radiological features and risk factors for early vs. late presentation.
AB  - Nonanastomotic biliary strictures (NAS) are a serious complication after
      orthotopic liver transplantation (OLT). The exact pathogenesis is unclear.
      Purpose of this study was to identify risk factors for the development of NAS
      after OLT. A total of 487 adult liver transplants with a median follow-up of 7.9
      years were studied. All imaging studies of the biliary tree were reviewed.
      Cholangiography was routinely performed between postoperative days 10-14 and
      later on demand. Localization of NAS at first presentation was categorized into 4
      anatomical zones of the biliary tree. Severity of NAS was semiquantified as mild,
      moderate, or severe. Donor, recipient, and surgical characteristics and variables
      were analyzed to identify risk factors for NAS. NAS developed in 81 livers
      (16.6%). Thirty-seven (7.3%) were graded as moderate to severe. In 85% of the
      cases, anatomical localization of NAS was around or below the bifurcation of the
      common bile duct. A large variation was observed in the time interval between OLT
      and first presentation of NAS (median 4.1 months; range 0.3-155 months). NAS
      presenting early (< or =1 year) after OLT were associated with preservation
      related risk factors. Cold and warm ischemia times were significantly longer in
      patients with early NAS compared with NAS presenting late (>1 year) after OLT
      (694 minutes vs. 490 minutes, P = 0.01, and 57 minutes vs. 53 minutes, P < 0.05,
      respectively), and early NAS were more frequently located in the central bile
      ducts. NAS presenting late (>1 year) after OLT were found more frequently in the
      periphery of the liver and were more frequently associated with immunological
      factors, such as primary sclerosing cholangitis, as the indication for OLT (24%
      vs. 45%, P < 0.05). By separating cases of NAS on the basis of the time of
      presentation after transplantation, we were able to identify differences in risk
      factors, indicating different pathogenic mechanisms depending on the time of
      initial presentation.

PMID- 17457933
TI  - Trends in post-liver transplant survival in patients with hepatitis C between
      1991 and 2001 in the United States.
AB  - It has been suggested that the post-liver transplantation (LT) survival rate of
      patients with hepatitis C virus infection (HCV) has declined in recent years. To
      compare the outcome of LT in patients with HCV at various time intervals between
      1991 and 2001, we used United Network for Organ Sharing data to compare the post
      LT survival of adult patients (age >18 years) with HCV with those without HCV. Of
      the 37,101 patients who underwent LT during the study period, 28,193 patients
      (HCV 7,459 and 20,734 non-HCV) were eligible for the study. On the basis of the
      time of transplantation, patients were divided into 3 groups: 1991-1993 (period
      1), 1994-1997 (period 2), and 1998-2001 (period 3). The patient and graft
      survival rates were adjusted for other known confounding variables that
      influenced outcomes. The 3-year patient survival rate was lower in HCV patients
      compared with non-HCV recipients (78.5% vs. 81.4%, hazard ratio 1.14, 95%
      confidence interval 1.05-1.23, P = 0.001). The graft (72.8%, 71.0%, and 69.8%)
      and patient (77.4%, 79.6%, and 78.5%) survival of HCV patients remained unchanged
      during study periods 1-3, respectively. However, the graft and patient survival
      rates of non-HCV recipients improved markedly during study periods 2 and 3
      compared with period 1. The graft and patient survival has remained unchanged
      between 1991 and 2001 in HCV recipients, but during the same period, there was a
      great improvement in survival among non-HCV recipients.

PMID- 17457934
TI  - Generation of a conditional knockout allele for mammalian Spen protein
      Mint/SHARP.
AB  - The Spen protein family is found in worms, flies, and mammals, and is implicated
      in diverse biological processes from embryogenesis to aging. Spen proteins have
      three N-terminal RNA recognition motifs and a C-terminal SPOC domain. The
      mammalian Spen proteins Mint and its human ortholog SHARP interact with the Notch
      signaling mediator RBP-J as well as Msx2 and several unliganded nuclear hormone
      receptors, and impart transcription-repressing activity to these molecules by
      recruiting corepressors through the SPOC domain. Despite these in vitro findings,
      Mint/SHARP's physiological role is largely unknown, because Mint germline
      knockouts are embryonic lethal. To analyze Mint/SHARP function in postnatal mice,
      we created Mint-floxed mice that allow the Cre/loxP-mediated conditional knockout
      of Mint. We analyzed Mint and RBP-J epistasis during Notch-dependent splenic B
      lymphocyte development, and found that Mint suppresses Notch signaling through
      RBP-J. In addition, Mint deficiency caused severe hypoplasia in postnatal brain,
      suggesting it may regulate neuronal cell survival.

PMID- 17457935
TI  - Nonanastomotic biliary strictures after liver transplantation, part 2:
      Management, outcome, and risk factors for disease progression.
AB  - Nonanastomotic biliary strictures (NAS) after orthotopic liver transplantation
      (OLT) are associated with high retransplant rates. The aim of the present study
      was to describe the treatment of and identify risk factors for radiological
      progression of bile duct abnormalities, recurrent cholangitis, biliary cirrhosis,
      and retransplantation in patients with NAS. We retrospectively studied 81 cases
      of NAS. Strictures were classified according to severity and location. Management
      of strictures was recorded. Possible prognostic factors for bacterial
      cholangitis, radiological progression of strictures, development of severe
      fibrosis/cirrhosis, graft survival, and patient survival were evaluated. Median
      follow-up after OLT was 7.9 years. NAS were most prevalent in the extrahepatic
      bile duct. Twenty-eight patients (35%) underwent some kind of interventional
      treatment, leading to a marked improvement in biochemistry. Progression of
      disease was noted in 68% of cases with radiological follow-up. Radiological
      progression was more prevalent in patients with early NAS and one or more
      episodes of bacterial cholangitis. Recurrent bacterial cholangitis (>3 episodes)
      was more prevalent in patients with a hepaticojejunostomy. Severe fibrosis or
      cirrhosis developed in 23 cases, especially in cases with biliary abnormalities
      in the periphery of the liver. Graft survival, but not patient survival, was
      influenced by the presence of NAS. Thirteen patients (16%) were retransplanted
      for NAS. In conclusion, especially patients with a hepaticojejunostomy, those
      with an early diagnosis of NAS, and those with NAS presenting at the level of the
      peripheral branches of the biliary tree, are at risk for progressive disease with
      severe outcome.

PMID- 17457936
TI  - Evaluation of modified CMC and CMC-PVA as miscible polymer blend membranes for
      hepatocytes.
AB  - CMC and CMC-PVA were blended either with type I collagen, BSA or CS to obtain
      biocompatible membranes for evaluation as potential hepatocyte culture
      substrates. Pure and modified forms of CMC showed distinct surface, mechanical,
      and cell attachment properties. While the hydrophilicity decreased, the
      mechanical stability and the porosity of CMC membranes increased after blending.
      Serum proteins were adsorbed by all types of membranes. Among eight membranes
      tested, collagen-modified CMC was found to be a suitable membrane material for
      hepatocyte culture, in terms of mechanical and cell interaction properties.

PMID- 17457937
TI  - Interface interactions of osteoblasts with structured titanium and the
      correlation between physicochemical characteristics and cell biological
      parameters.
AB  - Cellular behavior at the interface of an implant is influenced by the material's
      topography. However, little is known about the correlation between the biological
      parameters and the physicochemical characteristics of the biomaterial. We
      therefore modified pure titanium surfaces by polishing, machining, blasting with
      glass spheres, blasting with corundum particles, and vacuum plasma spraying to
      give progressively higher surface roughness. The material surface was
      characterized by SEM, surface profiling, and electrochemical methods. We revealed
      a correlation for integrin expression and formation, adhesion, spreading,
      proliferation, and bone sialo protein expression with the physicochemical
      parameters of the titanium surfaces.

PMID- 17457938
TI  - Improved mesenchymal stem cell seeding on RGD-modified poly(L-lactic acid)
      scaffolds using flow perfusion.
AB  - Arg-Gly-Asp (RGD) has been widely utilized to increase cell adhesion to three
      dimensional scaffolds for tissue engineering. However, cell seeding on these
      scaffolds has only been carried out statically, which yields low cell seeding
      efficiencies. We have characterized, for the first time, the seeding of rat
      mesenchymal stem cells on RGD-modified poly(L-lactic acid) (PLLA) foams using
      oscillatory flow perfusion. The incorporation of RGD on the PLLA foams improves
      scaffold cellularity in a dose-dependent manner under oscillatory flow perfusion
      seeding. When compared to static seeding, oscillatory flow perfusion is the most
      efficient seeding technique. Cell detachment studies show that cell adhesion is
      dependent on the applied flow rate, and that cell attachment is strengthened at
      higher levels of RGD modification.

PMID- 17457939
TI  - A degradable hyperbranched poly(ester amine) based on poloxamer diacrylate and
      polyethylenimine as a gene carrier.
AB  - Polyethylenimine (PEI) is a well-known cationic polymer which has high
      transfection efficiency due to its buffering effect. However, nondegradability,
      cytotoxicity, aggregation, and short-circulation time in vivo still need to be
      overcome for a successful gene delivery. Degradable, hyperbranched poly(ester
      amine)s (PEAs) based on poloxamer diacrylate and low molecular weight branched
      PEI, were successfully synthesized and evaluated as a nonviral gene carrier. The
      PEAs were obtained in significant yields through Michael type addition reaction
      of diacrylate monomers and low molecular weight branched PEI. Analysis of
      degradation products by the reduction in molecular weight demonstrated that PEAs
      degrade in a controlled fashion. The PEA showed good DNA binding ability and the
      sizes of complexes under physiological condition were below 150 nm, implicating
      its potential for intracellular delivery. It showed lower cytotoxicity in three
      different cell lines (A549, 293T, and HepG2) compared with PEI 25K. PEAs showed
      much higher transfection efficiencies in three cell lines compared with PEI 25K
      and PEI 1.8K, and revealed little serum dependency in A549 cell line when the
      content of poloxamer in the PEA was increased up to 30%.

PMID- 17457940
TI  - Synthesis and erosion properties of PEG-containing polyanhydrides.
AB  - To tailor the erosion rate of polyanhydrides while retaining their surface
      erosion characteristics, new three-component polyanhydrides of sebacic acid, 1,3
      bis(p-carboxyphenoxy)propane and poly(ethylene glycol) were synthesized. The
      hydrophilicity of the polymer increased and its mechanical strength decreased
      with increasing PEG content. Correspondingly, the erosion rate increases with
      increasing PEG content, whereas it decreases with increasing specimen thickness.
      This indicates that the incorporation of poly(ethylene glycol) into traditional
      two-component polyanhydrides retains their surface erosion properties while
      making the erosion rate tunable. The new polyanhydrides hold potential for drug
      delivery applications.

PMID- 17457941
TI  - The interaction of cationic polymers and their bisphosphonate derivatives with
      hydroxyapatite.
AB  - Conjugating proteins with bisphosphonates (BPs), a class of molecules with
      exceptional affinity to hydroxyapatite (HA), is a feasible means to impart bone
      affinity to protein-based therapeutic agents. To increase the targeting
      effectiveness while minimizing protein modification, a polymeric linker
      containing multiple copies of BPs could be constructed for protein conjugation
      and targeting to bone. Towards this goal, poly(L-lysine) (PLL) and
      poly(ethylenimine) (PEI) were utilized as the polymeric backbones to incorporate
      a BP, namely 2-(3-mercaptopropylsulfanyl)-ethyl-1,1-bisphosphonic acid (thiolBP),
      by using N-hydroxysuccinimidyl polyethylene glycol maleimide and succinimidyl-4
      (N-maleimidomethyl)-cyclohexane-1-carboxylate, respectively. In vitro and in vivo
      mineral affinity of the polymer-BP conjugates were determined in comparison with
      the unmodified polymers. The in vitro results indicated strong binding of the
      cationic polymers to HA in their unmodified form. BP conjugation did not enhance
      the inherent mineral affinity of the polymers; in contrast, certain modifications
      negatively affected the polymers' binding to the HA. In vivo results from a
      subcutaneous implant model in rats also showed no significant difference in
      mineral affinity of the BP modified and unmodified PEI. We conclude that thiolBP
      conjugation to the cationic polymers PLL and PEI was not beneficial for
      increasing the mineral affinity of the polymeric molecules. The strong
      interaction between the cationic polymers and HA may make the polymers suitable
      for imparting mineral affinity to bone-acting therapeutics.

PMID- 17457942
TI  - Human hepatocyte morphology and functions in a multibore fiber bioreactor.
AB  - The viability and liver specific functions of human hepatocytes in a multibore
      fiber bioreactor are reported. Human hepatocytes were cultured in the
      intraluminal compartment of the bioreactor. Human hepatocytes on the membranes
      maintained their round shape and showed focal adhesions as sites of interaction
      with the membrane surface. Cells in the bioreactor expressed liver specific
      functions, including synthetic and detoxification activity up to 14 d of culture.
      The results demonstrate that human hepatocytes cultured in the multibore fiber
      bioreactor are able to sustain the same in vivo liver functions in vitro.

PMID- 17457943
TI  - Preparation and characterization of a scaffold for vascular tissue engineering by
      direct-assembling of collagen and cells in a cylindrical geometry.
AB  - In the past 25 years, several efforts have been focused on developing vascular
      substitutes showing long-term patency when implanted in humans. In this study, we
      present our last findings in an ongoing project aiming to develop a tissue
      regenerated blood vessel from collagen-based scaffolds. A collagen-based scaffold
      with adequate biological properties was developed by directly assembling collagen
      and cells in a cylindrical geometry. The technique mainly involves the use of a
      ventilated rotating tube allowing smooth muscle cells to grow in a cylindrical
      collagen matrix. Scanning electron microscopy (SEM), histology, and cell cycle
      analyses were carried out in order to assess the biological potential of the cell
      based scaffold for further maturation. Compliance results showed that this
      technique allows cells to assemble in the collagen matrix, thus providing enough
      rigidity to the structure to be handled and mounted in a perfusion bioreactor for
      further growth and maturation.

PMID- 17457944
TI  - Novel physically crosslinked polyurethane-block-poly(vinyl pyrrolidone) hydrogel
      biomaterials.
AB  - Successful tissue repair and regeneration relies on the design of new
      biomaterials that can mediate cell interaction without inflicting undesirable
      responses. Novel physically crosslinked polyurethane-block-poly(vinyl
      pyrrolidone) hydrogel biomaterials were synthesized by the macroiniferter
      controlled radical polymerization method. The structures of the hydrogels were
      studied by FT-IR and (1)H NMR. Hydrogels with EWC up to 37 wt.-% were prepared.
      The presence of the PVP block significantly increased the hard-segment glass
      transition temperature. Vascular smooth muscle cell attachment and spreading on
      the hydrogels indicated that these materials have a potential for use as
      scaffolds in tissue engineering.

PMID- 17457945
TI  - Covalent grafting of fibronectin onto plasma-treated PTFE: influence of the
      conjugation strategy on fibronectin biological activity.
AB  - Surface coating of synthetic materials is often considered to improve biomedical
      devices biocompatibility. In this study, we covalently bound fibronectin (FN)
      onto ammonia plasma-treated PTFE via two crosslinkers, namely glutaric anhydride
      (GA) and sulfosuccinimidyl-4-(p-maleimidophenyl)butyrate (sulfo-SMPB). With
      respect to clean PTFE, cell adhesion increased markedly on both FN grafted
      surfaces, although it was twice higher on PTFE-GA-FN than on PTFE-SMPB-FN. ELISA
      experiments performed with a polyclonal antibody revealed that the amount of FN
      is identical on both surfaces while monoclonal antibody specific to the RGD
      binding site clearly demonstrated a greater availability when FN is surface
      grafted through GA. These results provide evidence of a variation in protein
      conformation correlated with the surface conjugation strategy.

PMID- 17457946
TI  - Chondroitin-4-sulfate: a bioactive macromolecule to foster vascular healing
      around stent-grafts after endovascular aneurysm repair.
AB  - Deficient healing after endovascular aneurysm repair with a stent-graft is
      thought to be related to pro-apoptotic environment in abdominal aortic aneurysms
      and inertness of graft materials. We developed a bioactive coating containing
      chondroitin-4-sulfate and assessed its potential to improve cell adhesion,
      viability and resistance to apoptosis on PET surfaces. Coatings of collagen type
      I and CS were prepared and characterized by DMMB, FT-IR, DSC, SEM and contact
      angle goniometry. Preliminary cell culture experiments with vascular smooth
      muscle cells showed increased adhesion and viability in serum-free medium on CS
      coated surfaces compared to control PET films.

PMID- 17457947
TI  - Selection bias due to immigration in pharmacoepidemiologic studies.
AB  - PURPOSE: To investigate the extent of selection bias due to exclusion of recent
      immigrants with respect to prevalence of antidiabetic drug use. METHODS: Data on
      antidiabetic drug redemptions were obtained from Odense University
      Pharmacoepidemiologic Database for the period 1992-2003 covering a population of
      approximately 470,000. Ordinary prevalence estimates based on drug redemptions
      during a run-in period for non-immigrants were compared to estimates based on the
      waiting time distribution (WTD) approach. The WTD method was used to compare
      estimates for non-immigrants to estimates for the entire population. RESULTS:
      When a run-in period of half a year was used and treatment cessation was
      accounted for, reasonable agreement between run-in estimates and WTD estimates
      was found, range of relative difference was -3.1% to 4.5%. Analyses using WTD
      method showed that prevalence among immigrants was approximately half that of non
      immigrants in each of the years 1993-2003, resulting in a relative bias (non
      immigrants vs. entire population) of approximately 1% for each year (range 0.73%;
      1.36%). Stratifying on age and sex made the bias vanish, except for ages under
      40. CONCLUSIONS: Selection bias due to immigration, when studying prevalence of
      use of antidiabetics, is small after controlling for age and sex. The WTD
      approach is useful for studying selection bias and should potentially replace the
      use of run-in periods for determining treatment status.

PMID- 17457948
TI  - Changing GPs' prescription patterns through guidelines and feedback. Intervention
      study.
AB  - PURPOSE: To investigate whether and how a multi-dimensional intervention
      including clinical guidelines on the choice of medical treatment in the primary
      and the secondary health care sector, and individual feedback to general
      practices about their own and other practices' prescription patterns in five
      Anatomical Therapeutic Chemical classification system (ATC)-groups was followed
      by changes in the practices' prescription pattern. METHODS: Prospective
      historical registry study and a questionnaire study of GPs' self-reported use of
      guidelines and feedback. RESULTS: In every ATC-group the number of prescribed
      defined daily doses (DDDs) kept growing after the intervention, while potential
      savings by DDD decreased. Individual practices' changes in the prescription
      pattern differed by ATC-group and practices with high potential savings/DDD
      before the intervention showed the greatest relative reduction in potential
      savings/DDD. The county's average cost/DDD for the five ATC-groups declined from
      above the Danish average before the intervention to a level below the average
      cost/DDD after the intervention. In the questionnaire study (response rate: 79%),
      69% of respondents had read the guidelines and 78% reported that the feedback
      influenced their prescription of drugs. CONCLUSIONS: The observed changes in drug
      costs and potential savings were not due to volume effects but a combination of
      price effects, including generic substitution and choice of less expensive
      analogues, demonstrating that it is possible to change GPs' prescription patterns
      without interfering with patients' access to treatment or with GPs' clinical
      freedom.'

PMID- 17457949
TI  - A phase II study of a THP-COP regimen for the treatment of elderly patients aged
      70 years or older with diffuse large B-cell lymphoma.
AB  - Pirarubicin (tetrahydropyranyl adriamycin: THP) is an anthracycline drug that
      reportedly has fewer cardiotoxic effects than doxorubicin. A phase II study was
      conducted in order to determine the efficacy of a treatment regimen incorporating
      THP, namely THP-COP in the treatment of elderly patients aged 70 years or older
      with diffuse large B-cell lymphoma (DLBCL). The treatment regimens for Group A
      (aged 70-79 years, n = 45) and Group B (aged 80 years or older, n = 16) consisted
      of cyclophosphamide, THP, vincristine, and prednisolone, repeated six times,
      every 3 weeks. The complete remission rate was 72.1%. The 5-year survival rate
      was 38.1%. For elderly patients with favourable prognostic factors, the 5-year
      survival rate was significantly better at 77.9% compared with 15.6% for patients
      with poor prognostic factors (p < 0.01). Death associated with the treatment
      regimen was not observed. We conclude that the THP-COP treatment regimen has
      fewer side effects and is very effective in the treatment of DLBCL in elderly
      patients, especially those with favourable prognostic factors. The present
      findings indicate the necessity of future studies investigating a combination
      therapy comprised of rituximab and THP-COP for the treatment of elderly patients
      with CD20-positive DLBCL.

PMID- 17457950
TI  - Optimizing information on drug exposure by collection of package code information
      in questionnaire surveys.
AB  - PURPOSE: The thorough analysis of special drug characteristics requires
      information on the specific brand of a drug. This information is often not sought
      in pharmacoepidemiologic surveys although in many countries packages are labelled
      with an unequivocal code (in Germany called Pharmazentralnummer (PZN)). We aimed
      to assess the benefit and quality of PZN information collected in self-completed
      questionnaires. METHODS: We performed a survey in 905 ambulatory patients who
      were asked to list brand name, strength, and the PZN of all drugs they were
      taking. RESULTS: The medication list was completed by 97.5% (n = 882) of the
      responding patients (mean age 67.3 years). Altogether 5543 drugs (100%) were
      mentioned in the questionnaires and for 4230 (76.3%) the exact drug package could
      be allocated on the basis of the PZN. When PZN was considered in addition to the
      drug name the quality of drug coding was significantly improved (p < 0.001) with
      regard to the allocation of drug package (74% versus 2%), brand (90% versus 70%),
      and strength (96% versus 86%). The time needed for drug coding was three times
      shorter. CONCLUSIONS: The high response rate and high fraction of correct PZN
      indicate that the collection of package code information is a valuable method to
      achieve more accurate drug data in questionnaire surveys and to facilitate the
      drug coding procedure.

PMID- 17457951
TI  - Cerebral white matter changes and rate of progression of dementia during
      cholinesterase inhibitor treatment: a retrospective cohort study.
AB  - BACKGROUND: Cerebral white matter changes (WMC) represent cerebrovascular disease
      (CVD) and are common in dementia. Cholinesterase inhibitors (ChEIs) are effective
      in Alzheimer's Disease (AD) with or without CVD, and in Dementia with Lewy Bodies
      (DLB). Predictors of treatment response are controversial. OBJECTIVE: To
      investigate the effect of WMC severity on rate of progression of dementia during
      treatment with ChEIs. METHODS: CT or MRI brain scans were rated for WMC severity
      in 243 patients taking ChEIs for dementia. Raters were blind to patients'
      clinical risk factors, dementia subtype and course of illness. Effects of WMC
      severity on rates of decline in cognition, function and behaviour were analysed
      for 140 patients treated for 9 months or longer. Analysis was performed for this
      group as a whole and within diagnostic subgroups AD and DLB. The main outcome
      measure was rate of change in Mini Mental State Examination (MMSE) score.
      Secondary measures were rates of change in scores on the Cambridge Cognitive
      Examination (CAMCOG), Instrumental Activities of Daily Living (IADL) and Clifton
      Assessment Procedures for the Elderly - Behaviour Rating Scale (CAPE-BRS).
      RESULTS: There was no significant association between severity of WMC and any
      specified outcome variable for the cohort as a whole or for patients with AD. In
      patients with DLB, higher WMC scores were associated with more rapid cognitive
      decline. CONCLUSIONS: Increased WMC severity does not influence clinical response
      to ChEI treatment in AD, but may hasten deterioration in ChEI-treated patients
      with DLB.

PMID- 17457952
TI  - ECT in the treatment of depressed elderly: lessons from a terminated clinical
      trial.

PMID- 17457953
TI  - An evaluation of two self-report screening measures for mood in an out-patient
      chronic heart failure population.
AB  - OBJECTIVE: To examine the criterion validity of the Hospital Anxiety and
      Depression Scale (HADS) and the Geriatric Depression Scale 15-item (GDS-15) in a
      community sample of Chronic Heart Failure (CHF) out-patients. METHODS: Eighty
      eight of 203 older adults with confirmed CHF responded to a postal survey and
      participated in a face-to-face interview. The GDS-15 and HADS were compared to
      diagnoses from the Structured Clinical Interview for DSM-IV (SCID-I), using a
      receiver operating characteristic (ROC) analysis and positive and negative
      predictive values, sensitivity and specificity for various cut-off points.
      RESULTS: For all depressive disorders, the area under the ROC curve for the GDS
      15 was 0.883 and a cut-off of 5 gave a sensitivity of 0.818 and a specificity of
      0.833. The area under the ROC curve for the HADS Depression (D) and Anxiety (A)
      were 0.889 and 0.941 respectively. At a cut-off of 7, the HADS-A gave a
      sensitivity of 0.938 and a specificity of 0.847. At a cut-off of 4, the HADS-D
      gave a sensitivity of 0.864 and a specificity of 0.788. CONCLUSIONS: The GDS-15
      and HADS are valid screening tools for detecting depression in aged CHF out
      patients. However, use of the HADS requires reduced cut-points to ensure that
      patients with mood disorder are not missed in this population.

PMID- 17457954
TI  - Prevalence and predictors of ocular manifestations of RA: is there a need for
      routine screening?
AB  - BACKGROUND: People with rheumatoid arthritis (RA) have an increased risk for eye
      problems caused by associated conditions or medication side-effects. Consequent
      visual impairment may increase the risk of falls or difficulties self
      administering medications. AIMS: The aim of the present study was to estimate the
      prevalence and predictors of ocular manifestations and visual impairment in a
      local sample of people with RA. The Visual Functioning Questionnaire (VFQ-25) was
      evaluated as a screening tool in people with RA. METHODS: Seventy-five
      participants with RA attended a visual screening clinic. Demographic, medication
      and disease characteristics were recorded, a full ophthalmological assessment was
      performed by an expert ophthalmologist and the VFQ-25, Health Assessment
      Questionnaire and Self-administered Comorbidity Questionnaire were completed.
      RESULTS: Twenty-nine participants (38.7%) had impaired visual acuity; this was
      correctable by appropriate refraction in 93.1%. The prevalence of cataracts was
      22.7% and this was predicted by older age and steroid use. An abnormal Schirmer's
      test, suggesting dry eyes, was seen in 70.7% of participants but only 12.0% were
      using artificial tears. Answers to the VFQ-25 suggested misinterpretation of
      questions as relating to disability attributed to arthritis rather than caused by
      visual impairment. CONCLUSIONS: Visual impairment does not appear to be
      particularly prevalent in RA, obviating the need for a screening programme.
      Utilization of the VFQ-25 as a screening tool in RA requires further
      consideration. The high prevalence of cataracts in participants on steroids
      emphasizes the need to prescribe the minimum required dose. The high prevalence
      of dry eyes suggests that a Schirmer's test should be performed regularly, with
      prescription of artificial tears if required.

PMID- 17457955
TI  - Prenatal diagnosis of a Turkish Bartsocas-Papas syndrome case with upper limb
      pterigia.
AB  - OBJECTIVES: Bartsocas-Papas syndrome is a severe, autosomal recessive syndrome.
      The major findings are severe popliteal webbing, ankyloblepharon, syndactyly,
      orofacial clefts, filiform bands, hypoplastic nose and ectodermal anomalies. We
      report a Turkish family with three affected pregnancies and a fetus prenatally
      diagnosed and terminated in pregnancy. METHODS: Obstetric ultrasound,
      amniocentesis and postmortem evaluation were done. RESULTS: Obstetric ultrasound
      presented lower limb malformations and facial findings. Postmortem fetal
      evaluation showed severe lower limb findings, less severe upper limb involvement
      and classical facial features of the syndrome. CONCLUSION: Upper limb pterygia is
      an unusual finding and reported in just two patients who were classified as
      having multiple pterygium syndrome, Aslan Type (605203) in the OMIM catalogue. We
      thought, as did many other authors, that those cases were consistent with
      Bartsocas-Papas syndrome and upper limb involvement less severe than lower limb
      findings as rare findings of this syndrome.

PMID- 17457956
TI  - Prenatal diagnosis of tracheo-oesophageal fistula and oesophageal atresia.
AB  - OBJECTIVES: To assess the accuracy of the prenatal ultrasound finding of
      subjectively small/absent stomach bubble in the prenatal diagnosis of tracheo
      oesophageal fistula and oesophageal atresia (TOF/OA). METHODS: A retrospective
      study of prenatal ultrasound scans showing small/absent stomach bubble was
      carried out between 1st January 1994 and 31st December 2003. RESULTS: There were
      62 cases with prenatally suspected (n = 40) and/or post-natally diagnosed (n =
      22) TOF/OA. Among the 40 cases of prenatally suspected TOF/OA 15 were thought to
      be isolated and 25 non-isolated. Of the 15 suspected isolated cases, 7 were
      normal and 8 had TOF/OA (5 isolated + 3 TOF/OA with another anomaly) at delivery.
      Among the 25 cases of prenatally suspected non-isolated TOF/OA, there was
      confirmation in only two cases, in the remaining 23 cases other anomalies were
      confirmed but TOF/OA was not present.Twenty-two babies with TOF/OA were
      identified in whom there had been no prenatal ultrasound suspicion on ultrasound
      scanning. Six had isolated TOF/OA and 16 had non-isolated TOF/OA. CONCLUSION: Of
      the 32 cases of confirmed TOF/OA,10 (31%) were suspected prenatally. If the
      TOF/OA was an isolated anomaly (11 cases), the prenatal detection rate was 45%.
      Interpretation of ultrasound findings suspicious of TOF/OA requires caution,
      particularly, when there are associated multiple anomalies on scan.

PMID- 17457957
TI  - Risk of myocardial infarction associated with selective COX-2 inhibitors: meta
      analysis of randomised controlled trials.
AB  - PURPOSE: To evaluate the risk of myocardial infarction (MI) associated with the
      use of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs). METHODS:
      Systematic review and meta-analysis of randomised controlled trials (RCTs) using
      a fixed-effect model to estimate the odds ratios (ORs) for risk of MI associated
      with coxibs compared against placebo, non-steroidal anti-inflammatory drugs
      (NSAIDs) and other coxibs. RESULTS: Fifty-five trials (99 087 patients) were
      included in the meta-analysis. The overall pooled OR for MI risk for any coxib
      compared against placebo was 1.46 (95%CI: 1.02, 2.09). We found celecoxib,
      rofecoxib, etoricoxib, valdecoxib and lumiracoxib were associated with higher MI
      risks compared against placebo. The pooled OR for any coxib compared against
      other NSAIDs was 1.45 (95%CI: 1.09, 1.93). Rofecoxib had a significantly higher
      risk of MI than naproxen (OR: 5.39; 95%: 2.08, 14.02) and valdecoxib had lower MI
      risk than diclofenac (OR: 0.14, 95%CI: 0.03, 0.73). There were no significant
      differences identified in the risk of MI from the available head-to-head
      comparisons of coxibs. CONCLUSIONS: Coxibs were associated with increased risks
      of MI when compared against placebo or non-selective NSAIDs. Differences in MI
      risk were also apparent between comparisons of individual NSAIDs. Future work
      should consider using individual patient data (IPD) meta-analysis to explore
      differences in MI risk between different subgroups of patients.

PMID- 17457958
TI  - Correlates of low-dosage treatment with antidepressants by psychiatrists and
      general practitioners.
AB  - BACKGROUND: The prescribing of low dosages of antidepressants has for many years
      been a matter of concern in the scientific literature. There is a little
      understanding of why physicians do not follow dosage recommendations and what
      factors influence medical decision-making. METHOD: In a drug utilisation
      observation study, treatment of 692 patients was monitored who were prescribed
      the tricyclic antidepressant doxepin by 80 general practitioners and 85
      psychiatrists. RESULTS: The mean maximum dosage per day was 83 mg/d. One hundred
      and fifty milligrams per day or more were prescribed for only 6.1% of the
      patients. There were significant differences between dosage groups: patients
      older than 65 received lower dosages (68 mg/d) as younger patients (84 mg/d),
      male patients higher dosages (94 mg/d) than females (79 mg/d), patients who had a
      mild depression with a score of 1-35 on the depression symptom scale received on
      average 68 mg/d, while patients with 36-74 got 100 mg/d. Physician speciality was
      not significantly related to dosage levels. In a logistic regression analysis,
      gender and Clinical Global Impression (CGI) at first examination remained factors
      that significantly predicted dosages of >or=125 mg/d. CONCLUSION: Low-dosage
      treatment with antidepressants is a rule rather than an exception. The
      prescribing pattern is not indiscriminate, but physicians follow an adaptive
      strategy and there is medical and theoretical evidence which supports their
      practice. Outcome research will have to be clarified in future studies as to what
      extent reference to such intervening variables can help to optimise individual
      dosage finding.

PMID- 17457959
TI  - Antiproliferative effects of some N-benzylideneanilines.
AB  - A series of Schiff bases including N-benzylideneaniline (NBA) nuclei were
      prepared. The chemical products obtained were characterized by mass spectometry
      (APCI), 1H NMR, and IR spectroscopy in order to seek their cytotoxic and
      proliferation effects on human small lung (A549) and cervical (HeLa) cancer cell
      lines with biochemical assays. All of the synthesized compounds showed
      antiproliferative effects to different extents.

PMID- 17457960
TI  - The relationship between severity of Alzheimer's disease and prevalence of
      comorbid depressive symptoms and depression: a systematic review.
AB  - OBJECTIVES: To gain more insight into the association between severity of
      Alzheimer's Disease (AD) and prevalence of comborbid depression. METHODS: A
      systematic literature review based on the Cochrane methodology was performed.
      PubMed, PsychINFO and EMBASE databases were searched for existing studies that
      fulfilled predefined inclusion criteria. The studies were divided into: (1) those
      that analysed the association between severity of AD and prevalence of depressive
      symptoms ('continuous' approach) and (2) those that investigated the association
      between severity of AD and diagnosed depression ('categorical' approach). The
      quality of existing studies was rated and the results were synthesized with a
      best evidence synthesis. RESULTS: Twenty-four studies fulfilled the inclusion
      criteria. Nineteen reported results for a continuous approach and seven for a
      categorical approach. Three of the four high quality studies within the
      continuous approach did not find a significant association between severity of AD
      and prevalence of depressive symptoms. None of the three high quality studies
      using the categorical approach found a significant association between the
      severity of AD and the prevalence of diagnosed depression. CONCLUSIONS: There is
      evidence for a lack of association between the severity of AD and the prevalence
      of comorbid depressive symptoms or diagnosed depression. Until new studies
      contradict this conclusion, prevention and intervention strategies for comorbid
      depression in AD should be aimed at all patients irrespective their disease
      severity.

PMID- 17457961
TI  - Acute cognitive effects of standardised Ginkgo biloba extract complexed with
      phosphatidylserine.
AB  - Recent data suggest that the complexation of standardised Ginkgo biloba extract
      (GBE) with soy-derived phospholipids enhances the bioavailability of GBE's active
      components. The current study therefore aimed to assess the comparative cognitive
      and mood effects of a low dose of GBE and products complexing the same extract
      with either phosphatidylserine or phosphatidylcholine. The study utilised a
      placebo-controlled, multi-dose, double-blind, balanced-crossover design. Twenty
      eight healthy young participants received 120 mg GBE, 120 mg GBE complexed with
      phosphatidylserine (Virtiva), 120 mg GBE complexed with phosphatidylcholine and a
      matching placebo, on separate days 7 days apart. Cognitive performance was
      assessed using the Cognitive Drug Research (CDR) computerised test battery and
      Serial Subtraction tasks immediately prior to dosing and at 1, 2.5, 4 and 6 h
      thereafter. The primary outcome measures were the four aspects of cognitive
      performance, which have previously been derived by factor analysis of CDR
      subtests. Levels of terpenoids (bilobalide, ginkgolide A and ginkgolide B) were
      concomitantly assessed in plasma samples taken pre-dose and at 3 and 6.5 h post
      dose.In keeping with previous research utilising the same methodology, 120 mg of
      GBE was not associated with markedly improved performance on the primary
      outcomes. However, administration of GBE complexed with phosphatidylserine
      resulted both in improved secondary memory performance and significantly
      increased speed of memory task performance across all of the post-dose testing
      sessions. Enhancement following GBE complexed with phosphatidylcholine was
      restricted to a modest improvement in secondary memory performance which was
      restricted to one post-dose time point. All three treatments were associated with
      improved calmness. There were no significant differences in post-dose levels of
      terpenoids between the Ginkgo containing treatments, although this latter finding
      may be attributable to methodological factors. Complexation with
      phosphatidylserine appears to potentiate the cognitive effects associated with a
      low dose of GBE. Further research is required to identify whether this effect is
      due to the complexation of the extracts, their mere combination, or the separate
      psychopharmacological actions of the two extracts.

PMID- 17457963
TI  - Function of longitudinal vs circular muscle fibers in esophageal peristalsis,
      deduced with mathematical modeling.
AB  - We summarize from previous works the functions of circular vs. longitudinal
      muscle in esophageal peristaltic bolus transport using a mix of experimental
      data, the conservation laws of mechanics and mathematical modeling. Whereas
      circular muscle tone generates radial closure pressure to create a local
      peristaltic closure wave, longitudinal muscle tone has two functions, one
      physiological with mechanical implications, and one purely mechanical. Each of
      these functions independently reduces the tension of individual circular muscle
      fibers to maintain closure as a consequence of shortening of longitudinal muscle
      locally coordinated with increasing circular muscle tone. The physiological
      function is deduced by combining basic laws of mechanics with concurrent
      measurements of intraluminal pressure from manometry, and changes in cross
      sectional muscle area from endoluminal ultrasound from which local longitudinal
      shortening (LLS) can be accurately obtained. The purely mechanical function of
      LLS was discovered from mathematical modeling of peristaltic esophageal transport
      with the axial wall motion generated by LLS. Physiologically, LLS concentrates
      circular muscle fibers where closure pressure is highest. However, the mechanical
      function of LLS is to reduce the level of pressure required to maintain closure.
      The combined physiological and mechanical consequences of LLS are to reduce
      circular muscle fiber tension and power by as much as 1/10 what would be required
      for peristalsis without the longitudinal muscle layer, a tremendous benefit that
      may explain the existence of longitudinal muscle fiber in the gut. We also review
      what is understood of the role of longitudinal muscle in esophageal emptying,
      reflux and pathology.

PMID- 17457964
TI  - The oesophageal zero-stress state and mucosal folding from a GIOME perspective.
AB  - The oesophagus is a cylindrical organ with a collapsed lumen and mucosal folds.
      The mucosal folding may serve to advance the function of the oesophagus, i.e. the
      folds have a major influence on the flow of air and bolus through the oesophagus.
      Experimental studies have demonstrated oesophageal mucosal folds in the no-load
      state. This indicates that mucosal buckling must be considered in the analysis of
      the mechanical reference state since the material stiffness drops dramatically
      after tissue collapse. Most previous work on the oesophageal zero-stress state
      and mucosal folding has been experimental. However, numerical analysis offers a
      promising alternative approach, with the additional ability to predict the
      mucosal buckling behaviour and to calculate the regional stress and strain in
      complex structures. A numerical model used for describing the mechanical
      behaviour of the mucosal-folded, three-layered, two-dimensional oesophageal model
      is reviewed. GIOME models can be used in the future to predict the tissue
      function physiologically and pathologically.

PMID- 17457962
TI  - Neuropathophysiology of functional gastrointestinal disorders.
AB  - The investigative evidence and emerging concepts in neurogastroenterology
      implicate dysfunctions at the levels of the enteric and central nervous systems
      as underlying causes of the prominent symptoms of many of the functional
      gastrointestinal disorders. Neurogastroenterological research aims for improved
      understanding of the physiology and pathophysiology of the digestive subsystems
      from which the arrays of functional symptoms emerge. The key subsystems for
      defecation-related symptoms and visceral hyper-sensitivity are the intestinal
      secretory glands, the musculature and the nervous system that controls and
      integrates their activity. Abdominal pain and discomfort arising from these
      systems adds the dimension of sensory neurophysiology. This review details
      current concepts for the underlying pathophysiology in terms of the physiology of
      intestinal secretion, motility, nervous control, sensing function, immuno-neural
      communication and the brain-gut axis.

PMID- 17457965
TI  - Finite element simulation of food transport through the esophageal body.
AB  - The peristaltic transport of swallowed material in the esophagus is a neuro
      muscular function involving the nerve control, bolus-structure interaction, and
      structure-mechanics relationship of the tissue. In this study, a finite element
      model (FEM) was developed to simulate food transport through the esophagus. The
      FEM consists of three components, i.e., tissue, food bolus and peristaltic wave,
      as well as the interactions between them. The transport process was simulated as
      three stages, i.e., the filling of fluid, contraction of circular muscle and
      traveling of peristaltic wave. It was found that the maximal passive intraluminal
      pressure due to bolus expansion was in the range of 0.8-10 kPa and it increased
      with bolus volume and fluid viscosity. It was found that the highest normal and
      shear stresses were at the inner surface of muscle layer. In addition, the peak
      pressure required for the fluid flow was predicted to be 1-15 kPa at the bolus
      tail. The diseases of systemic sclerosis or osteogenesis imperfecta, with the
      remodeled microstructures and mechanical properties, might induce the malfunction
      of esophageal transport. In conclusion, the current simulation was demonstrated
      to be able to capture the main characteristics in the intraluminal pressure and
      bolus geometry as measured experimentally. Therefore, the finite element model
      established in this study could be used to further explore the mechanism of
      esophageal transport in various clinical applications.

PMID- 17457966
TI  - Computation of flow through the oesophagogastric junction.
AB  - Whilst methods exist to indirectly measure the effects of increased flow or
      gastro-oesophageal refluxing, they cannot quantitatively measure the amount of
      acid travelling back up into the oesophagus during reflux, nor can they indicate
      the flow rate through the oesophago-gastric junction (OGJ). Since OGJ dysfunction
      affects flow it seems most appropriate to describe the geometry of the OGJ and
      its effect on the flow. A device known as the functional lumen imaging probe
      (FLIP) has been shown to reliably measure the geometry of and pressure changes in
      the OGJ. FLIP cannot directly measure flow but the data gathered from the probe
      can be used to model flow through the junction by using computational flow
      dynamics (CFD). CFD uses a set of equations known as the Navier-Stokes equations
      to predict flow patterns and is a technique widely used in engineering. These
      equations are complex and require appropriate assumptions to provide
      simplifications before useful data can be obtained. With the assumption that the
      cross-sectional areas obtained via FLIP are circular, the radii of these circles
      can be obtained. A cubic interpolation scheme can then be applied to give a high
      resolution geometry for the OGJ. In the case of modelling a reflux scenario, it
      can be seen that at the narrowest section a jet of fluid squirts into the
      oesophagus at a higher velocity than the fluid surrounding it. This jet has a
      maximum velocity of almost 2 ms(-1) that occurs where the OGJ is at its
      narrowest. This simple prediction of acid 'squirting' into the oesophagus
      illustrates how the use of numerical methods can be used to develop a better
      understanding of the OGJ. This initial work using CFD shows some considerable
      promise for the future.

PMID- 17457967
TI  - Mechanics of flow and mixing at antroduodenal junction.
AB  - The morphology of tissue structures composing the pyloric orifice is thought to
      play a role in effectively mixing aqueous gastric effluent with duodenal
      secretions. To understand the physical mechanisms leading to efficient digestion
      requires computational models that allow for analyses of the contributions of
      individual structural components. Thus, we have simulated 2-D channel flows
      through representative models of the duodenum with moving boundary capabilities
      in order to quantitatively assess the importance of notable features. A well
      tested flow solver was used to computationally isolate and compare geometric and
      kinematic parameters that lead to various characteristics of fluid motion at the
      antroduodenal junction. Scalar variance measurement was incorporated to quantify
      the mixing effectiveness of each component. It was found that the asymmetric
      geometry of the pyloric orifice in concert with intermittent gastric outflow and
      luminal constriction is likely to enhance homogenization of gastric effluent with
      duodenal secretions.

PMID- 17457968
TI  - Using computed tomography scans to develop an ex-vivo gastric model.
AB  - The objective of this research was to use abdominal computed tomography (CT)
      scans to non-invasively quantify anthropometrical data of the human stomach and
      to concomitantly create an anatomically correct and distensible ex-vivo gastric
      model. Thirty-three abdominal CT scans of human subjects were obtained and were
      imported into reconstruction software to generate 3D models of the stomachs.
      Anthropometrical data such as gastric wall thickness, gastric surface area and
      gastric volume were subsequently quantified. A representative 3D computer model
      was exported into a selective laser sintering (SLS) rapid prototyping machine to
      create an anatomically correct solid gastric model. Subsequently, a replica wax
      template of the SLS model was created. A negative mould was offset around the wax
      template such that the offset distance was equivalent to that of the gastric wall
      thickness. A silicone with similar mechanical properties to the human stomach was
      poured into the offset. The lost wax manufacturing technique was employed to
      create a hollow distensible stomach model. 3D computer gastric models were
      generated from the CT scans. A hollow distensible silicone ex-vivo gastric model
      with similar compliance to that of the human stomach was created. The
      anthropometrical data indicated that there is no significant relationship between
      BMI and gastric surface area or gastric volume. There were inter- and intra-group
      differences between groups with respect to gastric wall thickness. This study
      demonstrates that abdominal CT scans can be used to both non-invasively determine
      gastric anthropometrical data as well as create realistic ex-vivo stomach models.

PMID- 17457969
TI  - Anatomically realistic multiscale models of normal and abnormal gastrointestinal
      electrical activity.
AB  - One of the major aims of the International Union of Physiological Sciences (IUPS)
      Physiome Project is to develop multiscale mathematical and computer models that
      can be used to help understand human health. We present here a small facet of
      this broad plan that applies to the gastrointestinal system. Specifically, we
      present an anatomically and physiologically based modelling framework that is
      capable of simulating normal and pathological electrical activity within the
      stomach and small intestine. The continuum models used within this framework have
      been created using anatomical information derived from common medical imaging
      modalities and data from the Visible Human Project. These models explicitly
      incorporate the various smooth muscle layers and networks of interstitial cells
      of Cajal (ICC) that are known to exist within the walls of the stomach and small
      bowel. Electrical activity within individual ICCs and smooth muscle cells is
      simulated using a previously published simplified representation of the cell
      level electrical activity. This simulated cell level activity is incorporated
      into a bidomain representation of the tissue, allowing electrical activity of the
      entire stomach or intestine to be simulated in the anatomically derived models.
      This electrical modelling framework successfully replicates many of the
      qualitative features of the slow wave activity within the stomach and intestine
      and has also been used to investigate activity associated with functional
      uncoupling of the stomach.

PMID- 17457970
TI  - On the mechanical behavior of the human biliary system.
AB  - This paper reviews the progress made in understanding the mechanical behaviour of
      the biliary system. Gallstones and diseases of the biliary tract affect more than
      10% of the adult population. The complications of gallstones, i.e. acute
      pancreatitis and obstructive jandice, can be lethal, and patients with acalculous
      gallbladder pain often pose diagnostic difficulties and undergo repeated
      ultrasound scans and oral cholecystograms. Moreover, surgery to remove the
      gallbladder in these patients, in an attempt to relieve the symptoms, gives
      variable results. Extensive research has been carried out to understand the
      physiological and pathological functions of the biliary system, but the mechanism
      of the pathogenesis of gallstones and pain production still remain poorly
      understood. It is believed that the mechanical factors play an essential role in
      the mechanisms of the gallstone formation and biliary diseases. However, despite
      the extensive literature in clinical studies, only limited work has been carried
      out to study the biliary system from the mechanical point of view. In this paper,
      we discuss the state of art knowledge of the fluid dynamics of bile flow in the
      biliary tract, the solid mechanics of the gallbladder and bile ducts, recent
      mathematical and numerical modelling of the system, and finally the future
      challenges in the area.

PMID- 17457971
TI  - A framework for the modeling of gut blood flow regulation and postprandial
      hyperaemia.
AB  - After a meal the activity of the gut increases markedly as digestion takes place.
      Associated with this increase in activity is an increase in blood flow, which has
      been shown to be dependent on factors such as caloric content and constitution of
      the meal. Much qualitative work has been carried out regarding mechanisms for the
      presence of food in a section of gut producing increased blood flow to that
      section, but there are still many aspects of this process that are not fully
      understood. In this paper we briefly review current knowledge on several relevant
      areas relating to gut blood flow, focusing on quantitative data where available
      and highlighting areas where further research is needed. We then present new data
      on the effect of feeding on flow in the superior mesenteric artery. Finally, we
      describe a framework for combining this data to produce a single model describing
      the mechanisms involved in postprandial hyperaemia. For a section of the model,
      where appropriate data are available, preliminary results are presented.

PMID- 17457972
TI  - Towards a multiscale model of colorectal cancer.
AB  - Colorectal cancer (CRC) is one of the best characterised cancers, with extensive
      data documenting the sequential gene mutations that underlie its development.
      Complementary datasets are also being generated describing changes in protein and
      RNA expression, tumour biology and clinical outcome. Both the quantity and the
      variety of information are inexorably increasing and there is now an accompanying
      need to integrate these highly disparate datasets. In this article we aim to
      explain why we believe that mathematical modelling represents a natural tool or
      language with which to integrate these data and, in so doing, to provide insight
      into CRC.

PMID- 17457973
TI  - Advanced imaging and visualization in gastrointestinal disorders.
AB  - Advanced medical imaging and visualization has a strong impact on research and
      clinical decision making in gastroenterology. The aim of this paper is to show
      how imaging and visualization can disclose structural and functional
      abnormalities of the gastrointestinal (GI) tract. Imaging methods such as
      ultrasonography, magnetic resonance imaging (MRI), endoscopy, endosonography, and
      elastography will be outlined and visualization with Virtual Reality and haptic
      methods. Ultrasonography is a versatile method that can be used to evaluate
      antral contractility, gastric emptying, transpyloric flow, gastric configuration,
      intragastric distribution of meals, gastric accommodation and strain measurement
      of the gastric wall. Advanced methods for endoscopic ultrasound, three
      dimensional (3D) ultrasound, and tissue Doppler (Strain Rate Imaging) provide
      detailed information of the GI tract. Food hypersensitivity reactions including
      gastrointestinal reactions due to food allergy can be visualized by
      ultrasonography and MRI. Development of multi-parametric and multi-modal imaging
      may increase diagnostic benefits and facilitate fusion of diagnostic and
      therapeutic imaging in the future.

PMID- 17457974
TI  - Long-term outcome and prognostic factors of patients with hilar
      cholangiocarcinoma.
AB  - AIM: To evaluate the long-term outcome and prognostic factors of patients with
      hilar cholangiocarinoma. METHODS: Ninety-six consecutive patients underwent
      treatment for malignant hilar bile duct tumors during 1995-2005. Of the 96
      patients, 20 were initially treated with surgery (n = 2 R0 / n = 18 R1). In non
      operated patients, data analysis was performed retrospectively. RESULTS: Among
      the 96 patients, 76 were treated with endoscopic transpapillary (ERC, n = 45)
      and/or percutaneous transhepatic biliary drainage (PTBD, n = 31). The mean
      survival time of these 76 patients undergoing palliative endoscopic and/or
      percutaneous drainage was 359 +/- 296 d. The mean survival time of patients with
      initial bilirubin levels > 10 mg/dL was significantly lower (P < 0.001) than
      patients with bilirubin levels < 10 mg/dL. The mean survival time of patients
      with Bismuth stage II (n = 8), III (n = 28) and IV (n = 40) was 496 +/- 300 d,
      441 +/- 385 d and 274 +/- 218 d, respectively. Thus, patients with advanced
      Bismuth stage showed a reduced mean survival time, but the difference was not
      significant. The type of biliary drainage had no significant beneficial effect on
      the mean survival time (ERC vs PTBD, P = 0.806). CONCLUSION: Initial bilirubin
      level is a significant prognostic factor for survival of patients. In contrast,
      age, tumor stage according to the Bismuth-Corlette classification, and types of
      intervention are not significant prognostic parameters for survival. Palliative
      treatment with endoscopic or percutaneous biliary drainage is still suboptimal,
      new diagnostic and therapeutic tools need to be evaluated.

PMID- 17457975
TI  - Cadaveric liver transplantation for non-acetaminophen fulminant hepatic failure:
      a 20-year experience.
AB  - AIM: To investigate the long-term results of liver transplantation (LT) for non
      acetaminophen fulminant hepatic failure (FHF). METHODS: Over a 20-year period, 29
      FHF patients underwent cadaveric whole LT. Most frequent causes of FHF were
      hepatitis B virus and drug-related (not acetaminophen) liver failure. All
      surviving patients were regularly controlled at the out-patient clinic and none
      was lost to follow-up. Mean follow-up was 101 mo. RESULTS: One month, one-, five-
      and ten-year patient survival was 79%, 72%, 68% and 68%, respectively. One month,
      one-, five- and ten-year graft survival was 69%, 65%, 51% and 38%, respectively.
      Six patients needed early (< 2 mo) retransplantation, four for primary non
      function, one for early acute refractory rejection because of ABO blood group
      incompatibility, and one for a malignant tumor found in the donor. Two patients
      with hepatitis B FHF developed cerebral lesions peri-transplantion: One developed
      irreversible and extensive brain damage leading to death, and one suffered from
      deep deficits leading to continuous medical care in a specialized institution.
      CONCLUSION: Long-term outcome of patients transplanted for non-acetaminophen FHF
      may be excellent. As the quality of life of these patients is also particularly
      good, LT for FHF is clearly justified, despite lower graft survival compared with
      LT for other liver diseases.

PMID- 17457976
TI  - Surgical approaches of resectable synchronous colorectal liver metastases: timing
      considerations.
AB  - AIM: To compare the safety and efficacy of simultaneous versus two stage
      resection of primary colorectal tumors and liver metastases. METHODS: From
      January 1996 to May 2004, 103 colorectal tumor patients presented with
      synchronous liver metastases. Twenty five underwent simultaneous colorectal and
      liver surgery and 78 underwent liver surgery 1-3 mo after primary colorectal
      tumor resection. Data were retrospectively analyzed to assess and compare the
      morbidity and mortality between the surgical strategies. The two groups were
      comparable regarding the age and sex distribution, the types of liver resection
      and stage of primary tumors, as well as the number and size of liver metastases.
      RESULTS: In two-stage procedures more transfusions were required (4 +/- 1.5 vs 2
      +/- 1.8, pRBCs, P < 0.05). Chest infection was increased after the two-stage
      approach (26% vs 17%, P < 0.05). The two-stage procedure was also associated with
      longer hospitalization (20 +/- 8 vs 12 +/- 6 d, P < 0.05). Five year survival in
      both groups was similar (28% vs 31%). No hospital mortality occurred in our
      series. CONCLUSION: Synchronous colorectal liver metastases can be safely treated
      simultaneously with the primary tumor. Liver resection should be prioritized over
      colon resection. It is advisable that complex liver resections with marginal
      liver residual volume should be dealt with at a later stage.

PMID- 17457977
TI  - Beneficial effect of an antibody against interleukin-2 receptor (daclizumab) in
      an experimental model of hepatocyte xenotransplantation.
AB  - AIM: To investigate the use of Daclizumab (Dmab) as an immunosuppressive agent in
      an experimental model of hepatocyte xenotransplantation (XenoTx) in rats with
      fulminant hepatic failure (FHF). METHODS: Two white male New Zealand rabbits were
      used as donors and 68 Wistar rats as recipients. FHF was induced by intravenous
      application of dimethylnitrosamine (DMNA). The isolated hepatocytes of the
      rabbits were xenotransplanted into the spleen of the rats 24 h after FHF
      induction. Group A (n = 13): no treatment; Group B (n = 14): FHF and XenoTx;
      Group C (n = 14): FHF and XenoTx and cyclosporin (CsA); Group D (n = 14): FHF and
      XenoTx and Dmab; Group E (n = 13): FHF and XenoTx and CsA and Dmab. The rats were
      followed for 15 d. RESULTS: Statistical analysis showed better survival among
      groups D (92.86%) and E (76.92%) compared to group A (all rats died after 72 h),
      group B (28.57%) or group C (71.43%), although the differences were not
      statistically significant. Biochemical evaluation of the liver enzymes and
      histology confirmed satisfactory function and engraftment, respectively.
      CONCLUSION: This experimental model has shown the safe, effective and beneficial
      use of Dmab in a xenotransplantation model of rabbit hepatocytes in rats.

PMID- 17457978
TI  - Gene expression profile of esophageal cancer in North East India by cDNA
      microarray analysis.
AB  - AIM: To identify alterations in genes and molecular functional pathways in
      esophageal cancer in a high incidence region of India where there is a widespread
      use of tobacco and betel quid with fermented areca nuts. METHODS: Total RNA was
      isolated from tumor and matched normal tissue of 16 patients with esophageal
      squamous cell carcinoma. Pooled tumor tissue RNA was labeled with Cy3-dUTP and
      pooled normal tissue RNA was labeled with Cy5-dUTP by direct labeling method. The
      labeled probes were hybridized with human 10K cDNA chip and expression profiles
      were analyzed by Genespring GX V 7.3 (Silicon Genetics). RESULTS: Nine hundred
      twenty three genes were differentially expressed. Of these, 611 genes were
      upregulated and 312 genes were downregulated. Using stringent criteria (P < or =
      0.05 and > or = 1.5 fold change), 127 differentially expressed genes (87
      upregulated and 40 downregulated) were identified in tumor tissue. On the basis
      of Gene Ontology, four different molecular functional pathways (MAPK pathway, G
      protein coupled receptor family, ion transport activity, and serine or threonine
      kinase activity) were most significantly upregulated and six different molecular
      functional pathways (structural constituent of ribosome, endopeptidase inhibitor
      activity, structural constituent of cytoskeleton, antioxidant activity, acyl
      group transferase activity, eukaryotic translation elongation factor activity)
      were most significantly downregulated. CONCLUSION: Several genes that showed
      alterations in our study have also been reported from a high incidence area of
      esophageal cancer in China. This indicates that molecular profiles of esophageal
      cancer in these two different geographic locations are highly consistent.

PMID- 17457979
TI  - KN-93, a specific inhibitor of CaMKII inhibits human hepatic stellate cell
      proliferation in vitro.
AB  - AIM: To investigate the effects of KN-93, a CaMKII selective inhibitor on cell
      proliferation and the expression of p53 or p21 protein in human hepatic stellate
      cells. METHODS: Human hepatic stellate cells (LX-2) were incubated with various
      concentrations (0-50 micromol/L) of KN-93 or its inactive derivative, KN-92. Cell
      proliferation was measured by CCK-8 assay, and the expression of two cell cycle
      regulators, p53 and p21, was determined by SDS-PAGE and Western blotting.
      RESULTS: KN-93 (5-50 micromol/L) decreased the proliferation of human hepatic
      stellate cells in a dose-dependent manner from 81.76% (81.76% +/- 2.58% vs 96.63%
      +/- 2.69%, P < 0.05) to 27.15% (27.15% +/- 2.86% vs 96.59% +/- 2.44%, P < 0.01)
      after 24 h treatment. Incubation of 10 micromol/L KN-93 induced the cell growth
      reduction in a time-dependent manner from 78.27% at 8 h to 11.48% at 48 h.
      However, KN-92, an inactive derivative of KN-93, did not inhibit cell
      proliferation effectively. Moreover, analysis of cell cycle regulator expression
      revealed that KN-93 rather than KN-92 reduced the expression of p53 and p21.
      CONCLUSION: KN-93 has potent inhibitory effect on proliferation of LX-2 cells by
      modulating the expression of two special cell cycle regulators, p53 and p21.

PMID- 17457980
TI  - Strangulated diaphragmatic hernia presenting clinically as pericarditis.
AB  - A case of strangulation of the transverse colon in a traumatic left diaphragmatic
      hernia manifesting as pericarditis is reported. This is unusual because
      pericardial signs in traumatic diaphragmatic hernia have been previously
      described in association with direct pericardial injury. This is the only such
      case where electrocardiographic changes of pericarditis were seen without direct
      pericardial trauma. The possibility of internal herniation through a traumatic
      diaphragmatic hernia must be considered in patients with chest symptoms and a
      compatible history.

PMID- 17457981
TI  - Portal hypertensive duodenal polyp: a case report.
AB  - Abnormalities of gastric mucosa in patients with portal hypertension are well
      documented. Manifestations of portal hypertension in small bowel and colon are
      less common. Colonic polypoid lesions microscopically consisting of a normal
      mucosa, with dilatation of submucosal vessels, have been described. We here
      report the first case of portal hypertensive duodenal polyp, responsible for
      gastro-intestinal bleeding. Endoscopic treatment turned out to be successful.

PMID- 17457983
TI  - Endoscopic transcystic stent placement for an intrahepatic abscess due to
      gallbladder perforation.
AB  - Perforation of the gallbladder with cholecystohepatic communication is a rare
      cause of liver abscess. Because it is a rare entity, the treatment modality has
      not been fully established. We report for the first time a patient with an
      intrahepatic abscess due to gallbladder perforation successfully treated by
      endoscopic stent placement into the gallbladder who had a poor response to
      continuous percutaneous drainage.

PMID- 17457982
TI  - A case of mucosa-associated lymphoid tissue lymphoma forming multiple
      lymphomatous polyposis in the small intestine.
AB  - A 50-year old woman suffering from diabetes had a CT scan that revealed a diffuse
      thickening of small intestinal wall and swollen paraaortic lymph nodes. An
      esophagogastroduodenoscopy (EGD) confirmed multiple polypoid lesions in the
      duodenum and small intestine, and conventional histological testing revealed non
      specific inflammatory changes. Further examinations including the
      immunohistochemical profiles of the biopsied specimens led us to diagnose the
      lesion as a marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
      type, forming multiple lymphomatous polyposis sequentially spreading from
      duodenal bulb to terminal ileum. According to Lugano's classification, its
      staging was clinically diagnosed as stage II. Two courses of a standard CHOP
      (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and
      predonisolone) regimen with rituximab reduced the lesion and the patient had a
      almost complete response. A 5-year follow-up EGD and histological examinations
      detected no recurrence of the disease.

PMID- 17457984
TI  - Rectal angiolipoma: a case report and review of literature.
AB  - Angiolipoma is a rare vascular variant of the benign lipomatous tumors and is
      generally seen in subcutaneous tissues. We report a 70-year-old female with
      abdominal distension not related to rectal small polypoid mass with peduncule
      described as angiolipoma by histologically, and review the literature.

PMID- 17457985
TI  - Hepatic abscess induced by foreign body: case report and literature review.
AB  - Hepatic abscess due to perforation of the gastrointestinal tract caused by
      ingested foreign bodies is uncommon. Pre-operative diagnosis is difficult as
      patients are often unaware of the foreign body ingestion and symptoms and
      imagiology are usually non-specific. The authors report a case of 62-year-old
      woman who was admitted with fever and abdominal pain. Further investigation
      revealed hepatic abscess, without resolution despite antibiotic therapy. A liver
      abscess resulting from perforation and intra-hepatic migration of a bone coming
      from the pilorum was diagnosed by surgery. The literature concerning foreign body
      induced perforation of the gastrointestinal tract complicated by liver abscess is
      reviewed.

PMID- 17457986
TI  - Global. Refugees, women must be included in national HIV/AIDS treatment.

PMID- 17457987
TI  - Imaging fixed and embedded tissues with MALDI MS.

PMID- 17457988
TI  - The cervical-vaginal fluid proteome and possible biomarkers of preterm birth.

PMID- 17457989
TI  - New database for human metabolomics.

PMID- 17457990
TI  - [Radiographic changes in non-operated isolated sagittal suture synostosis].
AB  - PURPOSE: To characterize the spontaneous clinical course of isolated sagittal
      synostosis based on planar skull radiography. MATERIALS AND METHODS: In this
      retrospective analysis we evaluated a total of 155 radiographs of 55 children 2
      weeks to 9 years old. The sagittal, coronal and lambdoid sutures were evaluated
      on the basis of pairs of ap and lateral radiographs. The sutures were examined
      with respect to their boundary, activity, and conspicuity to be visualized (based
      on a 3-grade score system). Six selected points on the skull X-ray defined eight
      measured distances, three angles, and a width-length index. To document changes
      over time, the measurements were correlated to normal values. In addition, a
      correlation between suture activity and selected parameters was evaluated.
      RESULTS: The sagittal suture could be continuously or partially depicted in more
      then half of all radiographs taken during the first year of life, The measured
      distances and angles were concordant with results from the literature. With
      increasing age, the width-length index deviated from standard values while other
      parameters approximated the norm. CONCLUSION: In the case of children younger
      than twelve months, the sagittal suture appears radiologically open in many cases
      despite clear-cut scaphocephaly. Definite signs of progressive plurisutural
      fusion were not found in this series. The dolichocephalic deformity remained
      unchanged while some signs of scaphocephalic appearance actually improved.

PMID- 17457991
TI  - Retraction notice to 'Abnormal DNA content predicts the occurrence of carcinomas
      in non-dysplastic oral white patches' [Oral Oncol. 37 (2001) 558-565].

PMID- 17457992
TI  - Retraction notice to 'When is an oral leukoplakia premalignant?' [Oral Oncol. 38
      (2002) 813-814].

PMID- 17457993
TI  - Retraction notice to 'Cyclooxygenase-2 (COX-2) expression in high-risk
      premalignant oral lesions' [Oral Oncol. 39 (2003) 497-505].

PMID- 17457994
TI  - The pricing conundrum.

PMID- 17457995
TI  - Price controls seen as key to Europe's drug innovations lag.

PMID- 17457996
TI  - Retraction notice to 'Molecular based treatment of oral cancer' [Oral Oncol. 39
      (2003) 749-758].

PMID- 17457997
TI  - New HIV drug classes on the horizon.

PMID- 17457998
TI  - An audience with... Arti Rai.

PMID- 17457999
TI  - Drug developer strategies to boost competitiveness.

PMID- 17458000
TI  - Telbivudine.

PMID- 17458001
TI  - We must not fail the children of Africa.

PMID- 17458002
TI  - What's good food and what's for breakfast?

PMID- 17458003
TI  - Out of the box.

PMID- 17458004
TI  - Emergency medicine in the blogosphere: the irreverent wit of the specialty's
      unofficial voice.

PMID- 17458005
TI  - IOM report ignites new debate on who should practice emergency medicine.

PMID- 17458006
TI  - Issue in tribute to John (Jack) Pearce.

PMID- 17458007
TI  - Evidence-based emergency medicine/systematic review abstract. Role of early
      supported discharge in acute stroke patients.

PMID- 17458008
TI  - Proceedings of the 58th International Symposium on Crop Protection, Gent,
      Belgium, May 23, 2006. Part 1.

PMID- 17458009
TI  - Proceedings of the 58th International Symposium on Crop Protection, Gent,
      Belgium, May 23, 2006. Part III.

PMID- 17458012
TI  - Funding. Intervention denied over implementation of new CARE Act.

PMID- 17458010
TI  - The song remains the same.

PMID- 17458013
TI  - Global. U.N. details refugees' rights to antiretrovirals.

PMID- 17458014
TI  - Lambda Legal releases report on state of U.S. HIV stigma.

PMID- 17458015
TI  - ADA. Chicago employee's retaliation claim survives dismissal.

PMID- 17458016
TI  - Discrimination. Employer faces charges for firing HIV-positive worker.

PMID- 17458017
TI  - Treatment. Negligence absent in inmate's AIDS drug deprivation claim.

PMID- 17458018
TI  - California's HIV privacy shaken amid mailing mistake.

PMID- 17458019
TI  - Bibliography. Current world literature. Biliary tract.

PMID- 17458020
TI  - Current World Literature. Nutrition and the intensive care unit.

PMID- 17458021
TI  - Raju Kucherlapati talks about personalised medicine: breathing new life into old
      drugs. Interview by Steve Carney.

PMID- 17458022
TI  - [Infections in vascular reconstruction].

PMID- 17458023
TI  - [Josef Koncz (1916-1988)--pioneer of cardiac surgery].
AB  - Josef Koncz (1916-1988) was until given emeritus status in 1982 director of the
      Department of Cardiothoracic and Vascular Surgery, which was specifically founded
      for him in Goettingen, Germany. By the fusion of three different surgical
      branches the University hospital of Goettingen took over the role of a pacemaker
      and initiated a standard in the development of this new specialty in Germany. The
      scientific and clinical work done by the Department of Cardiothoracic and
      Vascular Surgery was shaped by the personality of the surgeon and scientist Josef
      Koncz. He was a successful surgeon and innovative pioneer in one person. Already
      in 1956, he started open-heart surgery and proceeded this technique in an
      impressing series. In 1965 he was the first in Germany who operated upon the
      transposition of the great vessels by Mustard's method and developed together
      with his long-standing assistant, Huschang Rastan, an operation technique to
      extend the left-ventricular outflow tract combined with tunnel-shaped subvalvular
      aortic valve stenosis. Another essential element of his work is related to the
      establishment of the Cardiothoracic and Vascular Surgery as an independent
      specialty, ending in the foundation of the German Society for Thoracic and
      Cardiovascular Surgery in 1971.

PMID- 17458024
TI  - AORN guidance statement: mass casualty, triage, and evacuation.

PMID- 17458025
TI  - Recommended practices for selection and use of packaging systems for
      sterilization.

PMID- 17458026
TI  - [How should surgery maintain its leading role in interprofessional cooperative
      relations in medicine].

PMID- 17458027
TI  - [Management of pain].

PMID- 17458028
TI  - [Evaluation of pain].

PMID- 17458030
TI  - [Euthanasia].

PMID- 17458029
TI  - [3/6 Venous ulcers of the leg].

PMID- 17458031
TI  - The effect of a proposed change to fiber-counting rules in ASTM International
      Standard D7200-06.

PMID- 17458032
TI  - [The surgeon and informed consent].

PMID- 17458033
TI  - A clinical study of skin changes in pregnancy.
AB  - BACKGROUND: During pregnancy profound immunologic, metabolic, endocrine and
      vascular changes occur, that are responsible for the changes of the skin and its
      appendages, both physiologic and pathologic. AIMS: We undertook a clinical study
      to find out the frequency and pattern of skin changes in pregnant women. METHODS:
      All consecutive pregnant women were included in the study. RESULTS: A total of
      607 pregnant women were included in this study. Of these, 303 (49.9%) pregnant
      women were primigravida and 304 (51.1%) were multigravida. Skin changes grouped
      into: physiological changes (all cases), specific dermatoses (22 cases) and other
      dermatoses affected by pregnancy (125 cases). Most common physiological changes
      were pigmentary alterations seen in 555 (91.4%) followed by striae seen in 484
      (79.7%) cases. Of the various specific dermatoses of pregnancy, pruritic
      urticarial papules and plaques of pregnancy (PUPPP) was the most common disorder
      (14 cases) followed by pruritus gravidarum (5 cases). The most common dermatoses
      affected by pregnancy were candidal vaginitis (17 cases), acne vulgaris (15
      cases), skin tags (15 cases), eczemas (14 cases). CONCLUSION: This study brings
      into focus various skin changes during pregnancy in south India.

PMID- 17458034
TI  - Inflammatory pruritic nodules and plaques on the face.

PMID- 17458035
TI  - Development of the Massachusetts School Nurse Research Network (MASNRN): A
      Practice-Based Research Network to improve the quality of school nursing
      practice.
AB  - When school nurses embrace evidence-based practice (EBP), higher-quality care is
      provided to students, their families, and the larger community. Despite this,
      school nursing has been slow to embrace EBP. Practice-Based Research Networks
      (PBRNs), which capitalize on the combined strengths of clinicians and researchers
      to study clinical questions, are one approach to overcoming barriers towards
      advancing evidence-based practice (EBP) in school nursing. This article will
      briefly review EBP and PBRNs. The development of Massachusetts School Nurse
      Research Network (MASNRN), a PBRN designed to investigate health issues common
      across schools and to validate school nursing practice, will then be described.
      Details regarding MASNRN's mission, governance, communications systems, staffing,
      and network maintenance and funding will be explicated. MASNRN can serve as a
      model for PBRN development within the broader school nursing community.

PMID- 17458037
TI  - Duplicate publication.

PMID- 17458036
TI  - How health affects small business in South Africa.
AB  - Preventable and treatable diseases have taken a devastating human and economic
      toll on many developing countries. That economic toll is likely to be
      underestimated because most studies focus on productivity losses in the formal,
      or large-firm, sector; yet, a large portion of the population of developing
      countries works in the informal sector in very small businesses, either as an
      owner-worker or as an employee. It is plausible that ill health might affect
      small businesses most severely, possibly putting the entire business at risk.
      This Issue Brief summarizes a three-year study that tracks small businesses in
      Durban, South Africa, and investigates the connection between the owner's health
      and business growth, survival, or closure. The results bolster the economic case
      for investing resources in the prevention and treatment of disease in developing
      countries.

PMID- 17458038
TI  - Ethiopian adventure. Interview by Lisa Leano.

PMID- 17458039
TI  - Lanthanum: new drug. Hyperphosphataemia in dialysis patients: more potential
      problems than benefits.
AB  - (1) In dialysis patients with chronic renal failure, hyperphosphataemia can cause
      osteorenal dystrophy, leading to bone pain, fractures and excess cardiovascular
      mortality. In addition to a low-phosphorus diet and dialysis, phosphorus
      chelators are usually needed to control blood phosphorus levels. The first choice
      is calcium carbonate, and sevelamer is an alternative. (2) Lanthanum carbonate, a
      phosphorus chelator, is now also licensed for the treatment of hyperphosphataemia
      in dialysis patients with chronic renal failure. (3) In addition to three dose
      finding placebo-controlled studies, clinical evaluation includes 2 comparative
      randomised unblinded trials: one 6-month trial versus calcium carbonate and a 2
      year trial versus other phosphorus chelators. During these trials, lanthanum was
      no more effective than the comparators in terms of effects on the mortality rate,
      incidence of fractures, or blood phosphorus level. (4) During these trials,
      adverse events attributed to treatment were more frequent with lanthanum than
      with the other phosphorus chelators. The main problems were gastrointestinal
      disorders (nausea, vomiting, diarrhoea, constipation and abdominal pain),
      headaches, seizures, and encephalopathy. (5) The accumulation of lanthanum in the
      bones and brain is troubling. The known long-term adverse effects of aluminium,
      another trivalent cation with weak gastrointestinal absorption, suggest that
      caution is also required with lanthanum. (6) In practice, when a phosphorus
      chelator is needed to treat hyperphosphataemia in dialysis patients with chronic
      renal failure, calcium carbonate is the first choice and sevelamer remains the
      best alternative.

PMID- 17458040
TI  - H&HN eight decades of health care. The 1940s.

PMID- 17458041
TI  - Practical ethics. Time to tell surgeon to retire?

PMID- 17458042
TI  - Metformin: new indication. Useful for some children with type 2 diabetes.
AB  - (1) Type 2 diabetes is rare in children. Lifestyle measures are the cornerstone
      of treatment. When they fail to control hyperglycaemia and when drug therapy is
      envisaged, insulin has long been the only approved drug. (2) Metformin is now
      indicated to treat hyperglycaemia due to type 2 diabetes in children over 10
      years of age, alone or in combination with insulin. (3) In a randomised double
      blind placebo-controlled trial involving 82 children, the mean reduction in HbA1c
      level with metformin was statistically significant after 8 weeks of treatment
      (about 1% in absolute values, versus no change in the placebo group). (4) In a
      randomised unblinded trial the addition of metformin to ongoing insulin therapy
      in 106 children reduced both mean HbA1c levels and weight gain after one year of
      treatment. About one-third of children treated with metformin were able to stop
      using insulin and maintain satisfactory glycaemic control. (5) The adverse
      effects of metformin in children are the same as those reported in adults (mainly
      frequent but mild gastrointestinal disorders). (6) Metformin is taken orally,
      making it more convenient to use than insulin, especially in long-term treatment.
      (7) In practice, although the assessment of metformin in children with type 2
      diabetes is limited, metformin is a useful oral addition or alternative to
      insulin injection. Metformin addition to ongoing insulin therapy allows some
      patients to stop using insulin altogether.

PMID- 17458043
TI  - Ivabradine: new drug. Best avoided in stable angina.
AB  - (1) The first-line symptomatic treatment for stable angina is a betablocker such
      as atenolol. Some calcium channel blockers such as verapamil, and the potassium
      channel agonist amlodipine, are second-line alternatives. Long-acting nitrate
      derivatives have poorly documented efficacy but can be used as adjuvants or as
      third-line treatments. (2) Ivabradine is derived from verapamil but appears to
      have a different mechanism of action, mainly lowering the heart rate. It was
      approved for sale in Europe through the centralised procedure for second-line
      treatment of stable angina. (3) Clinical evaluation of ivabradine only includes
      randomised controlled trials versus two other anti-angina drugs: atenolol and
      amlodipine. Three double-blind randomised controlled trials lasting 3 to 4
      months, based on surrogate exercise endpoints, failed to show that ivabradine was
      any more effective than atenolol or amlodipine, or even more effective than
      placebo in patients already treated with amlodipine. (4) In two one-year double
      blind randomised controlled trials comparing ivabradine with atenolol or
      amlodipine in a total of 704 patients, ivabradine was no more effective than the
      comparators in preventing angina attacks. (5) In head-to-head comparisons,
      serious coronary events were significantly more frequent with ivabradine than
      with atenolol (3.8% versus 1.5%). Severe arrhythmias were also more frequent with
      ivabradine than with atenolol (1.3% versus 0.7%) or amlodipine (0.6% versus
      0.2%). (6) Ivabradine provokes phosphenes (flashing lights, etc.) in about 17% of
      patients in the short term. Information is inadequate to assess possible risks of
      retinal toxicity in the long term. (7) Ivabradine is metabolised by cytochrome
      P450 isoenzyme CYP 3A4; there is therefore a potentially high risk of
      pharmacokinetic interactions. (8) In practice, for long-term preventive treatment
      of angina it is better to avoid ivabradine and to use better-documented
      treatments: preferably a betablocker, or, if a betablocker cannot be used,
      verapamil or amlodipine.

PMID- 17458044
TI  - Nitisinone: new drug. Type 1 tyrosinemia: an effective drug.
AB  - (1) Type 1 hereditary tyrosinemia is a rare disease due to an enzyme deficiency.
      It is associated with life-threatening liver disorders, starting during the very
      first months of life. If left untreated (other than with a diet low in tyrosine
      and phenylalanine), most patients die during childhood. Liver transplantation is
      currently the only treatment to have an effect on survival. (2) Nitisinone is the
      first drug to be approved in Europe for the treatment of type 1 hereditary
      tyrosinemia. (3) An international non comparative trial included 207 patients
      treated with nitisinone in addition to a diet low in tyrosine and phenylalanine.
      Children treated before the age of 6 months had a far better four-year survival
      rate than patients treated previously with dietary measures alone (94% versus
      60%). The difference was even greater in the subgroups treated before the age of
      two months (88% versus 29%). When disease onset occurred after the age of 6
      months, the ten-year survival rate was about 85% with nitisinone, compared to 60%
      with dietary measures alone. Only one patient had a neurological crisis during
      nitisinone therapy. Early nitisinone treatment also reduced the incidence of
      liver transplantation (13%, compared to 25% with dietary measures alone). (4)
      Nitisinone seems to have few adverse effects, mainly consisting of
      thrombocytopenia, leukopenia, cutaneous disorders, and various visual disorders
      (most of which resolve spontaneously). There may also be a risk of seizures. (5)
      In practice, nitisinone seems to provide a major benefit for children with type 1
      tyrosinemia, provided they are diagnosed and treated during the first 6 months of
      life. Adverse effects appear to be acceptable but need to be monitored.

PMID- 17458045
TI  - Sertindole: new drug. Another "atypical" neuroleptic; QT prolongation.
AB  - (1) The first-line drug for the treatment of schizophrenic disorders is a
      neuroleptic such as haloperidol. Amisulpride may be preferable when haloperidol
      causes unacceptable neurological reactions. Overall, the risk-benefit balance of
      more recent, so-called atypical neuroleptics is no better. (2) Sertindole, a
      neuroleptic, was first marketed in 1996 in several European countries before
      being withdrawn two years later because of numerous cardiac adverse effects. It
      has once again been approved and should soon be available on the French market.
      (3) Two comparative double-blind trials suggest that a daily sertindole dose of
      24 mg is about as effective as 10 mg of haloperidol. Sertindole was no more
      effective than risperidone in a trial comparing these two drugs. (4) Like other
      'atypical' neuroleptics, sertindole has few short-term neurological adverse
      effects (extrapyramidal syndrome) at the doses used in clinical trials. However,
      it causes weight gain. Sertindole also has alpha blocking properties, which can
      cause postural hypotension and reduce ejaculate volume; it also has atropinic
      effects (constipation, dry mouth, etc.). (5) Sertindole provokes a dose-dependent
      increase in the QT interval more frequently than haloperidol in comparative
      trials, and apparently more frequently than other 'atypical' neuroleptics such as
      risperidone and olanzapine. Sertindole has been suspected of increasing
      cardiovascular mortality but this has not been established. (6) Sertindole is
      metabolised by cytochrome P450 isoenzymes CYP 2D6 and CYP 3A4, hence a high risk
      of pharmacokinetic interactions. (7) In practice, when haloperidol has to be
      withdrawn because of adverse effects, especially neurological reactions, it is
      better to continue to resort to amisulpride, for example, with close monitoring
      of adverse effects, rather than expose patients to the potential dangers of
      sertindole.

PMID- 17458047
TI  - Iron 0.5 mg: new drug. A welcome low-dose formulation for neonates.

PMID- 17458046
TI  - Interferon alfa-2b and ribavirin: new indication. In children: more risks than in
      adults.
AB  - (1) There is a far lower seroprevalence of hepatitis C virus (HCV) infection in
      children and adolescents (0.2% to 0.4%) than in adults. In childhood, the
      principal route of infection is mother-child transmission during pregnancy, while
      in adolescence transmission is mainly through certain at-risk behaviour
      (piercing, tattooing and drug injection). In adults with HCV infection, the
      standard treatment is a combination of peginterferon alfa and ribavirin. (2) 125
      children aged 3 to 16 years were treated for 48 weeks in two non comparative
      trials. HCV RNA was undetectable in plasma in 46% of children six months after
      treatment cessation (36% for genotype 1 infection, 81% for other genotypes), a
      proportion similar to that generally seen in adults. It is not known whether the
      interferon alfa-2b + ribavirin combination slows the progression of histological
      lesions or prevents clinical complications of HCV infection. (3) Psychological
      disorders, particularly depression and suicidal tendencies, are the main adverse
      effects of treatment, especially in children. Growth retardation can also occur,
      mainly due to gastrointestinal disorders linked to interferon alfa-2b (loss of
      appetite, nausea and vomiting, diarrhoea). Catch-up growth appears to occur
      during the six months after treatment cessation. (4) The combination of
      interferon alfa-2b and ribavirin appears to have similar virological efficacy in
      children to that seen in adults. Adverse effects, especially those of a
      psychological nature, remain frequent.

PMID- 17458048
TI  - Rivastigmine: new indication. Dementia and Parkinson's disease: no thank you!
AB  - In patients with both Parkinson's disease and dementia, a placebo-controlled
      trial has confirmed that the adverse effects of rivastigmine outweigh its
      benefits. It is better to carefully adjust ongoing antiparkinsonian treatments
      than to add an anticholinesterase.

PMID- 17458049
TI  - Bicalutamide.
AB  - Non metastatic prostate cancer: avoid over-interpretation of flawed clinical
      trial evidence.

PMID- 17458050
TI  - Rosuvastatin: renal disorders and rhabdomyolysis.
AB  - (1) Rosuvastatin was not evaluated for its impact on morbidity or mortality. In
      premarketing trials its adverse effects seemed similar to those observed with
      other statins. In addition, there were questions concerning renal adverse
      effects, particularly dose-dependent proteinuria. Inadequate information was
      available to know whether the risk of rhabdomyolysis differed from that of other
      statins. (2) A review of adverse events reported to the FDA in late 2004 showed
      that reports of renal and muscular adverse events were more frequent with
      rosuvastatin than with other statins currently on the market. (3) Regulatory
      agencies analysed their results and issued warnings, but they withheld the raw
      data. This is regrettable, especially given the frequent use of the drug, the
      specific risks associated with this class, and the questions that were left
      unanswered in its initial clinical evaluation. Healthcare professionals and the
      public need access to more precise data on rosuvastatin. (4) In practice, it is
      better to select the two statins with the most thorough clinical assessments,
      namely simvastatin and pravastatin.

PMID- 17458051
TI  - Asthma: fatal exacerbations with long-acting beta2 agonist therapy without
      concomitant steroid therapy.
AB  - (1) In France, two long-acting inhaled beta2 agonists (salmeterol and formoterol)
      are marketed for long term symptomatic treatment of asthma, in combination with
      antiinflammatory treatment with an inhaled steroid. (2) A double-blind placebo
      controlled trial of salmeterol in about 26 000 patients was stopped prematurely
      in 2003 due to an excess of serious asthma attacks and asthma-related deaths in
      the salmeterol group. There were 13 asthma-related deaths after 28 weeks of
      salmeterol therapy, versus only three in the placebo group, for a relative risk
      of about 4 and a 95% confidence interval of 1.2 to 15.3. (3) This increased
      mortality was mainly observed in the subgroup of patients who were not using a
      steroid (53% of all patients). Nine of these patients died while taking
      salmeterol versus none on placebo. (4) Three smaller trials showed an increase in
      severe asthma attacks in patients using formoterol without a steroid. For
      example, in one trial nine of 271 patients on formoterol had severe asthma
      attacks, versus two of 277 patients on placebo. A meta-analysis of 19 placebo
      controlled trials of long-acting beta2 agonists showed an increase in severe
      asthma attacks in both adults and children. Exacerbations have also been
      attributed to salmeterol, including in patients using a steroid. (5) In practice,
      for long-term treatment, long-acting beta2 agonists must never be used without
      concomitant inhaled steroid therapy.

PMID- 17458052
TI  - Clinical state of the patients with periodontitis, IL-1 polymorphism and
      pathogens in periodontal pocket--is there a link? (An introductory report).
AB  - PURPOSE: According to last years' research, polymorphism of IL-1 has an influence
      on the progression of periodontal disease. Oral mouth microflora can also have an
      effect on the disease process. The aim of the work was to evaluate the amount of
      microbacterial pathogens in the periodontal pockets of patients with positive and
      negative genotype. MATERIAL AND METHODS: Study group comprised of 16 patients,
      aged 25-50 years. Only patients with severe generalized form of chronic
      periodontititis were included into the study. After clinical examination patients
      were subjected to the IL-1 genotype evaluation (Genotype PST, Hain Lifescience
      GmbH, Germany) and PCR examination of selected bacteria pathological for
      periodontium (Perio-Analyse, Pierre Fabre Medicament, France). RESULTS: 7 out of
      16 individuals were diagnosed as genotype positive (alleles 2 for genes IL-1A and
      IL-1B). Genetically positive individuals had greater mean pocket depth, clinical
      attachment loss and percentage of pockets deeper than 4 mm. Although in both
      groups similar bacterial pathogens have been identified, greater amounts of
      bacteria have been counted in group with positive genotype. Total count of
      bacteria from so-called "red complex" (P. gingivalis, T. forsythensis, T.
      denticola), and "orange complex" (F. nucleatum, P. micros, P. intermedia, C.
      rectus) were respectively 3-fold and 2-fold higher in group with positive
      genotype, despite the fact that group was smaller (7 vs 9 persons with negative
      genotype). Number and species of bacteria seems to correlate with pocket depth,
      clinical attachment loss, and percentage of pockets deeper than 4 mm. CONCLUSION:
      Observed association may have an influence on increased severity of periodontal
      disease in patients with positive genotype.

PMID- 17458053
TI  - Polymorphism in interleukin-1beta gene and the risk of periodontitis in a Polish
      population.
AB  - PURPOSE: The aim of the present study was to explore an association between IL-1B
      polymorphism and periodontal disease in patients with chronic periodontitis and
      subjects with aggressive periodontitis in a Polish population. In multivariate
      logistic regression the association of the following parameters: genotype, age,
      sex, smoking status, and approximal space plaque index (API) > 50% with the risk
      of periodontitis was analyzed. MATERIAL AND METHODS: Fifty-two unrelated patients
      suffering from periodontitis, 20 of them with generalized aggressive
      periodontitis and 32 with generalized advanced chronic periodontitis were
      enrolled into the study. Control group consisted of 52 healthy volunteers,
      without signs of periodontitis. IL-1B(+3954) polymorphism was determined using
      the polymerase chain reaction-restriction fragment length polymorphism (PCR
      RFLP). RESULTS: There were no significant differences in the distribution of IL
      1B(+3954) genotypes and alleles between periodontal patients either with chronic
      or aggressive periodontitis and the controls. A predisposing genotype consisting
      of allele 2 was carried by 34.4% of subjects with chronic periodontitis, 25.0% of
      subjects with aggressive periodontitis, and 40.3% of healthy subjects.
      Multivariate logistic regression analysis revealed significant association of age
      (p = 0.003), smoking (p =0.03), and API > 50% (p = 0.002) with the appearance of
      aggressive periodontitis, as well as API > 50% (p < 0.001) with chronic
      periodontitis. CONCLUSIONS: The study revealed no association of IL-1B
      polymorphism and the risk of aggressive and chronic periodontitis. The risk of
      aggressive periodontitis was significantly associated with age, smoking, and oral
      hygiene where as chronic periodontitis with oral hygiene only.

PMID- 17458054
TI  - Comparative research concerning clinical efficiency of three surgical methods of
      periodontium recessions treatment in five-year observations.
AB  - PURPOSE: The aim of this study was a comparative analyses of clinical treatment
      efficiency of periodontium recessions after the application of double pedicle
      bilateral flap (DPBF), coronally repositioned flap in combination with connective
      tissue graft (CRF-CTG), coronally advanced flap in combination with guided tissue
      regeneration using collagen membranes (GTR-CM). MATERIAL AND METHODS: Research
      material consisted of 37 people (71.2% of initial patient number), including 27
      women at the age from 17 to 53. All those people had single or multiple
      recessions, in I or II Miller's class, with the depth more than 2 mm. There were
      estimated 98 covered recessions of which 33 after DPBF, 41 after CRF-CTG and 24
      after GTR-CM. The clinical estimation of recession level before surgeries and
      after 12, 24, 60 months was done with the usage of the following parameters:
      recession depth (RD), recession width (RW), clinical attachment level (CAL) and
      keratinized tissue hight (HKT). There was also done an ultrasonic measurement of
      keratinized tissue thickness (TKT) in two groups of patients who had undergone
      surgeries CRF-CTG and GTR-CM. After 12, 24 and 60 months there were measured: an
      average percentage of a root coverage (% ARC), a percentage index of the complete
      root coverage (% CRC) and the percentage of complete coverage (CRC). RESULTS:
      Five-year inter group analyses of three surgical methods of recession treatment
      did not show any significant differences among surgeries for the following
      parameters: RD, CAL and TKT. The value of RD after DPBF was 0.85 mm, after CAF
      CTG was 0.83 mm and after GTR-CM 0.38 mm. There was a substantial difference of
      values such as ARC the best result of which was for the method GTR-CM (90%) and
      next for CRF-CTG (82%), CRC% and CRC with the best result for the methods GTR-CM
      (90%; 87.5%) and CRF-CTG (82.8%; 61%). CONCLUSIONS: The authors' observations
      show that methods GTR-CM and CRF-CTG are mostly predictable and enable the stable
      coverage of periodotium recession during five-year observations.

PMID- 17458055
TI  - Autogenous bone and platelet-rich plasma (PRP) in the treatment of intrabony
      defects.
AB  - PURPOSE: Obtaining an answer to the question whether autogenous bone in
      combination with PRP give a therapeutical effect in the form of periodontal
      ligament attachment regeneration. Defining the degree of elimination of a
      convenient environment for subgingival bacterial plaque by reduction of
      periodontal pocket depth and periodontitis. MATERIAL AND METHODS: Twenty-six
      systematically healthy patients with diagnosed chronic and advanced periodontitis
      (24 females and 2 males) were selected for the study. In general 72 periodontal
      infrabony pockets were treated. Clinically the following indexes were examined
      and measured: 1. Plaque Index by Silness and Loe. 2. Sulcus Bleeding Index by
      Muhlemann and Son. 3. Clinical Attachment Level (mm). 4. Pocket Depth (mm). 5.
      Gingival Recession (mm). 6. Tooth mobility with the use of Periotest. 7. Degree
      of alveolar bone loss with the use of Engelberger, Marthaler and Rateitschak
      index - EMR Index. RESULTS: At 12 months after treatment the following results
      were noted: Mean value of attachment level regeneration 3.47 mm. Mean value of
      pocket depth decreased by 3.7 mm. Mean value of tooth mobility reduction by
      48.3%. Megeneration of alveolar bone by 9.24%. CONCLUSIONS: 1. Autogenous bone
      with added PRP in treatment of intrabony defects caused by periodontitis have
      given significant clinical improvement of the periodontal tissues. 2. The
      combination of PRP and autogenous bone caused the elimination of a convenient
      environment for subgingival bacterial plaque eliminating periodontitis.

PMID- 17458056
TI  - Periodontitis as a risk factor of coronary heart diseases?
AB  - BACKGROUND: Unstable atherosclerotic plaque is a dangerous clinical state,
      possibly leading to acute coronary deficiency resulting in cardiac infarction.
      Inflammatory factor's role in creating pathological lesions in the endothelium of
      coronary vessels is frequently raised. This state may be caused by bacteria able
      to initiate clot formation in blood vessel and destabilizing atherosclerotic
      plaque already present. Source of these pathogens are chronic inflammatory
      processes occurring in organism, among them periodontal disease as one of more
      frequent. Aim of the work was to evaluate incidence of selected anaerobic
      bacteria in subgingival plaque and in atherosclerotic plaque in patients treated
      surgically because of coronary vessels' obliteration. METHODS: Study was
      performed on 20 individuals with chronic periodontitis. Subgingival plaque was
      collected from periodontal pockets deeper than 5 mm DNA test was used for marking
      eight pathogens responsible for periodontal tissues destruction. In the same
      patients, as well as in 10 edentulous individuals material from atherosclerotic
      plaque was collected during by-pass implantation procedure, and identical DNA
      testing occurred. RESULTS: In 13 of 20 patients pathogens most frequent in severe
      chronic periodontitis were found in coronary vessels. In 10 cases those bacteria
      were also present in atherosclerotic plaque. Pathogens linked with periodontal
      disease were also found in 7 of 10 edentulous individuals. Most frequently marked
      bacteria were: Porphyromonas gingivalis and Treponema denticola. CONCLUSIONS: It
      seems that advancement of periodontal disease does not have influence on bacteria
      permeability to coronary vessels. Important is the presence of active
      inflammatory process expressed by significantly higher bleeding index in patients
      with marked bacteria in atherosclerotic plaque.

PMID- 17458057
TI  - Evaluation of the product based on Recaldent technology in the treatment of
      dentin hypersensitivity.
AB  - PURPOSE: The aim of the study was to evaluate the efficiency of GC Tooth Mousse
      in the treatment of patients with dentin hypersensitivity caused by various
      factors. MATERIAL AND METHODS: The evaluation was carried out on 101 teeth with
      dentin hypersensitivity in 13 patients. Patients with gingival recession and
      exposed dental necks and those with non-carious lesions at the initial stage were
      selected. The initial examination was to evaluate the intensity of pain inducted
      by a stream of the air syringe and by probing the tooth surface. It was repeated
      directly after the preparation application, after 15 minutes, after 1 and 4
      weeks. RESULTS: After the medicine application, the number of teeth reacting with
      strong or extremely strong pain decreased (from almost 80% to 37.62%). The
      percentage of teeth reacting with mild pain increased by 15% and the number of
      teeth which did not react to the cold air stream also increased by 27.72%. The
      values after 15 minutes were similar. A week later, the percentage of teeth with
      very strong pain was elevated and so was the percentage of medium pain. On the
      other hand, the number of teeth without pain and with mild pain decreased twice.
      After one month the percentage distribution was close to the results obtained
      after 7 days. CONCLUSIONS: 1. GC Tooth Mousse preparation, based on Recaldent
      technology reveals insufficient effectiveness and short-term therapeutic effect
      in treating hypersensitivity of dentine. 2. It seems that soothing the pain by GC
      Tooth Mousse should be regarded rather as an additional remineralizing effect of
      the medicine.

PMID- 17458058
TI  - Evaluation of bone loss at single-stage and two-stage implant abutments of fixed
      partial dentures.
AB  - INTRODUCTION: Fixed partial dentures (FPDs) can be supported on implant abutments
      only or on single-stage and two-stage implants and teeth. PURPOSE: The purpose of
      this study was a comparative analysis of bone loss at the single-stage and two
      stage implant abutments of fixed partial dentures used to restore missing teeth
      classified as Class I or Class II according to the Kennedy classification.
      MATERIAL AND METHODS: 32 patients were treated by using 49 FPDs supported on
      implants and teeth worn for 2-6 years. Bone loss at the implant abutments of FPDs
      was evaluated by one examiner using a special ruler with a measuring scale and
      images of implants. Measurements were conducted at 26 single-stage implants and
      50 two-stage implant abutments based on panoramic radiographs. RESULTS:
      Statistical analysis showed that the mean bone loss at implants after 2 years was
      0.70 mm +/- 0.50. The mean bone loss at implants after 6 years was 1.73 mm +/-
      0.41. The bone loss of the alveolar ridge at the single-stage implants was
      greater than at the two-stage implants but it was not statistically significant.
      CONCLUSION: Prosthetic treatment of missing teeth classified as Class I or II
      according to the Kennedy classification with FPDs may result in bone loss less
      than 2 mm after 6 years. Both single-stage and two-stage intraosseous implants
      can be suitable for the implant-prosthetic treatment of patients with alar lack
      of teeth.

PMID- 17458059
TI  - The evaluation of lysozyme concentration and peroxidase activity in non
      stimulated saliva of patients infected with HIV.
AB  - PURPOSE: The aim of the study was the comparison of lysozyme concentration and
      peroxidase activity in mixed, non-stimulated saliva of HIV-positive patients and
      healthy subjects. MATERIAL AND METHODS: The study was carried out in the group of
      37 patients infected with HIV. The control group comprised of non-infected
      individuals, counterpart of the examined group. Mixed non-stimulated saliva,
      collected using expectoration method in the amount of 3-5 ml 2 hours after meal,
      was used for the study. Saliva samples were centrifuged, divided into portions
      200 microl each, and stored at -80 degrees C. Peroxidase activity was determined
      using the method by Mansson-Rahemtull et al. Lysozyme concentrations were
      determined with the use of radial immunodiffusion method, ready-made kits (Human
      NL Nanorid plate--The Binding Site Ltd., UK). RESULTS: Higher concentrations of
      lysozyme as well as peroxidase activity were observed in the group of patients
      with HIV as compared to the control group, and they were 35.08 microg/ml, 46.74
      IU/1, 21.3 microg/ml, 37.73 IU/l, respectively. The difference was statistically
      significant only in case of peroxidase activity. CONCLUSIONS: 1. HIV infection
      triggers immune mechanisms, that are manifested by the increase in salivary
      enzymes responsible for local non-specific resistance. 2. The immunological
      resistance decrease, manifested by the drop of the absolute number of CD4
      lymphocytes T, is compensated by the increase in lysozyme concentration and
      peroxidase activity in non-stimulated saliva of HIV-positive patients.

PMID- 17458060
TI  - Preliminary evaluation of morphological parameters of the saliva in patients
      undergoing orthodontic treatment.
AB  - PURPOSE: In recent years, many reports have focused on clinical changes in the
      oral cavity of orthodontic patients, manifested in general inflammation of the
      mucosa. In order to better understand histopathological alterations in the mouth
      and the use of easily available diagnostic material, we decided to assess the
      morphology of salivary cells at different time points of treatment with
      orthodontic appliances. MATERIAL AND METHODS: The study material included non
      stimulated saliva obtained from 21 orthodontic patients and 11 healthy secondary
      school students (controls). After fixation in 96% ethanol the smears were stained
      with PAS + hematoxylin or H+E, and using the methods of May-Grunwald-Giemsa and
      Feulgen. RESULTS: As revealed by the histopathological examinations of saliva
      smears, patients treated with intra-oral fixed orthodontic appliances showed
      morphological changes in oral epithelial cells and in the number of leukocytes as
      compared to the control group. The changes were most pronounced in the first
      months of treatment. CONCLUSIONS: The preliminary data indicate that orthodontic
      patients develop changes in the composition and morphology of salivary cells, the
      intensity of which depends on the time of exposure to the appliance.

PMID- 17458061
TI  - Preliminary evaluation of saliva composition in allergic patients subjected to
      orthodontic treatment; morphological examination.
AB  - PURPOSE: Intra-oral fixed orthodontic appliances, so frequently used in the
      treatment of malocclusions, may cause pathomorphological changes in the mouth and
      can be a potential source of antigen stimulation. Therefore, the aim of the
      current study was to assess the changes in salivary cells of orthodontically
      treated allergic patients. MATERIAL AND METHODS: The study material was the non
      stimulated saliva samples collected from 28 allergic patients subjected to
      orthodontic treatment with intra-oral fixed appliances and from 11 healthy
      secondary school students (controls). After fixation in 96% ethanol, saliva
      smears were stained with PAS + hematoxylin or H+E, and using the methods of May
      Grunwald-Giemsa and Feulgen. The microscopic analysis was made of oral epithelial
      cells and inflow elements, with regard to their shape, size, the nucleus-to
      cytoplasm ratio and nuclear chromatin condensation. RESULTS: The results of
      preliminary investigations indicate that allergic patients with fixed orthodontic
      appliances exhibit changes in the morphology and composition of salivary cells as
      compared to control patients. Differences in the morphological picture were most
      pronounced in the first months of orthodontic treatment. CONCLUSIONS: It was
      shown that the number and morphology of salivary cells in allergic patients
      altered in response to ions released from dental alloys. Thus, saliva can be used
      as diagnostic material.

PMID- 17458062
TI  - The effect of temperature, acidification, and alkalization changes as well as
      ethanol on salivary cathepsin D activity.
AB  - The activity of salivary cathepsin D undergoes inactivation at the temperature of
      50-60 degrees C and at pH of 2.0 and pH of 8.0-10.0. The enzyme activity is also
      decreased by high concentrations of ethanol and high-proof alcoholic beverages.
      The factors should be taken into consideration in the evaluation of salivary
      cathepsin D activity.

PMID- 17458063
TI  - Local argyrosis of oral mucosa or amalgam tattoo. A problem in diagnosis and
      treatment.
AB  - The authors, basing on three cases published by different authors in the years
      1995-2003, discuss the problem of diagnosis and treatment of local gingival
      argyrosis and amalgam tattoo. Treatment methods carried out consisted of the
      following procedures free gingival graft, subepithelial connective tissue graft
      in a two-step procedure and subepithelial connective tissue graft without flap
      coverage. In the authors opinion in some cases a connective tissue graft does not
      need flap coverage, therefore a dual blood supply is not necessary.

PMID- 17458064
TI  - Occurrence rate of oral Candida albicans in denture wearer patients.
AB  - PURPOSE: The aim was to determine the fungi occurrence rate in the oral cavity of
      denture wearer patients in comparison to those without dentures. MATERIAL AND
      METHODS: The examinations were conducted in patients treated in two clinical
      departments of the University Hospital. Demographic data and those connected with
      basic diseases were collected and the evaluation concerning dentition and oral
      hygiene was performed. Samples for mycological examinations from the tongue
      dorsa, palatal mucosa, and mucosal surfaces of dentures were collected from
      patients with dentures while tongue and palate swabs were taken from those
      without dentures. For culture and identify of fungi standard methods were used.
      RESULTS: Dental and mycological examinations were performed in 95 patients, out
      of which 57 (60.0%) used complete or partial dentures and 38 (40.0%) had their
      own dentition (without dentures). Oral cavity revealed only growth of Candida
      albicans species, more frequently in patients with dentures (38/57; 66.7%) than
      in those without dentures (11/ 38; 28.9%) (p = 0.0003). C. albicans statistically
      significantly more frequently was isolated in denture wearer patients with
      diabetes mellitus (p = 0.0207) and without diabetes (p = 0.0376) comparing to
      such groups of patients but without dentures. Among 32 patients with diabetes
      mellitus, 14 (43.8%) revealed C. albicans; this rate was comparable with 9/23
      (39.1%) patients without diabetes (p > 0.05). A similar analysis, conducted in 25
      surgical patients with abdominal cancer and 15--without--cancers, did not show
      statistically significant differences in the incidence rate of C. albicans; it
      also concerned denture wearers (14/16; 87.5%) and non-wearing dentures (5/9;
      55.6%) (p > 0.05) with cancer. In 37 (64.9%) wearer patients denture stomatitis
      was observed, associated mainly with C. albicans infections (29/37; 78.4%).
      CONCLUSIONS: 1) Mycological findings from the present study do not indicate that
      diabetes mellitus or advanced cancer has a significant effect on oral
      colonisation by Candida albicans or other species of Candida genus. 2) The
      occurrence rate of oral Candida albicans in patients with dentures (diabetic and
      non-diabetic, cancer and non-cancer patients) was higher than in patients without
      dentures (p < 0.05).

PMID- 17458065
TI  - Aerobic and anaerobic bacteria in subgingival and supragingival plaques of adult
      patients with periodontal disease.
AB  - PURPOSE: Clinical, epidemiological and microbiological examinations of adult
      patients with periodontal disease. MATERIAL AND METHODS: The study of population
      consisted of 21 subjects (13 female and 8 male) aged 38-58 years, treated in the
      Outpatient Department of Periodontology. Dental examinations were performed at an
      artificial light and using a WHO periodontometer, a mirror and a probe.
      Periodontal status was assessed by determination of the probing pocket depth
      (CPI), gingival state (GSBI according to Muhlemann and Son), and oral hygiene
      index (according to Silness and Loe). Material for microbiological examination
      was collected from subgingival and supragingival plaques of each patient.
      Additionally, pus was obtained from 8 patients and periodontal pocket fluid from
      2 patients. The samples were examined for the presence of aerobic and anaerobic
      bacteria and Candida yeasts. Standard procedures were used for culture and
      identification of bacteria and fungi. RESULTS: Candida yeasts were not isolated
      from adults with periodontal disease. In 19/21 patients, cultures of both aerobic
      and anaerobic bacteria from subgingival and supragingival plaque samples were
      positive. A total of 42 bacterial strains were isolated from subgingival plaques,
      of which 24 (57.1%) belonged to 7 anaerobic species and 18 (42.9%) to 12 aerobic
      species (p > 0.05). There were more aerobic (33/53; 62.3%) than anaerobic
      bacteria (20/53; 37.7%) (p < 0.05) in supragingival plaques. Anaerobes were
      isolated more frequently than aerobes from the abscess (p < 0.05). CONCLUSIONS:
      1) In adult patients with periodontal disease, Gram-positive anaerobes, including
      Peptostreptococcus, were the predominant bacteria in the subgingival plaque. 2)
      While in the supragingival plaque, Gram-positive aerobic cocci (Streptococcus and
      Staphylococcus) were predominant.

PMID- 17458066
TI  - Aerobic bacteria in the oral cavity of patients with removable dentures.
AB  - PURPOSE: Determination of bacterial composition in the oral cavity of patients
      with removable dentures and with own dentition (without dentures). MATERIAL AND
      METHODS: Bacteriological investigations were performed in 55 patients from the
      department of internal medicine (32 diabetic patients) and 40 patients treated in
      surgical department (25 patients with malignancy). Palate mucosa and tongue dorsa
      swabs were collected from two groups of patients, and additionally swabs from
      mucosal part of denture surfaces in prosthetic patients. Cultures in oxygenic and
      microaerophilic (5% CO2) conditions were conducted on solid non-selective and
      selective media as well as media enriched with 5% sheep blood. Standard
      procedures of bacterial culture and identification were applied. RESULTS: Among
      95 of examined patients, 57 (60.0%) with removable dentures and 38 (40.0%) had
      their own dentition. As far as prosthetic patients were concerned, the rate of
      bacterial isolations from palate, tongue dorsa and denture plaque swabs were
      generally comparable (p > 0.05); in number and species compositions.
      Statistically significant differences were observed in the bacterial composition
      of denture plaques, palate and tongue dorsa in patients with and without
      abdominal cancers. Patients without cancer did not reveal staphylococci and
      enteric bacteria in the samples from a various sites of their oral cavities.
      These bacteria were most common in cancer patients. Similar (in number and
      species) composition of bacteria occurred in palate and tongue swabs in patients
      without dentures (p > 0.05). The incidence rate of aerobic bacteria in denture
      plaques and palatal mucosa of patients with (37/57; 64.9%) and without (20/57;
      35.1%) denture associated stomatitis were comparable (except for Neisseria spp.).
      CONCLUSIONS: 1) Generally, there were no statistically significant differences in
      species composition of bacteria isolated from the hard palate and tongue dorsa in
      patients with and without removable dentures. 2) Staphylococcus spp. and Gram
      negative enteric bacilli were isolated more often from denture plaque, palate and
      tongue dorsa of cancer patients than from patients without cancer (p < 0.05). 3)
      Staphylococcus spp. was isolated more frequently from denture plaques of diabetic
      patients compared with non-diabetic patients (p < 0.05). 4) No significant
      differences observed in isolation frequencies (%) of aerobic bacteria in denture
      plaques and palatal mucosa of patients with and without denture associated
      stomatitis.

PMID- 17458067
TI  - Effect of sodium fluoride on the morphological picture of the rat liver exposed
      to NaF in drinking water.
AB  - PURPOSE: Due to its efficacy in caries prophylaxis and easy application, sodium
      fluoride (NaF) is still used for caries prevention in the form of fluoridated
      drinking water, fluoride tablets, fluoridated salt or milk. Effect of fluorides
      on various metabolic levels in hard and soft tissues, namely respiration as well
      as carbohydrate, protein, enzymatic and vascular metabolism, can disturb
      detoxication of fluorine compounds administered orally. The study objective was
      morphological examination of the liver of young and mature rats exposed to NaF in
      drinking water from conception till maturity, as well as after its withdrawal.
      MATERIAL AND METHODS: In the initial stage of the experiment, 30 female Wistar
      rats, 180-200 g body weight, were divided into 3 groups: one control and two
      experimental groups (I, II). Female rats in the experimental groups received
      fluorine in aqueous solutions of sodium fluoride (NaF) at a concentration of 10.6
      mg NaF/dm3 (group I) and 32.0 mg NaF/dm3 (group II). RESULTS: The
      pathomorphological changes observed in the liver, particularly of young rats
      exposed,to fluorides at superoptimal doses can help determine to what degree oral
      fluoride caries prevention is safe and whether it should be implemented. The
      transitory nature of pathomorphological changes in hepatocytes indicates adaptive
      potentials or defence mechanisms against orally administered sodium fluoride.

PMID- 17458068
TI  - Effect of chlorhexidine mouthrinse on cathepsin C activity in human saliva.
AB  - Chlorhexidine is an active agent commonly used against dental plaque in the mouth
      apart from fluorides applied to prevent caries. It is contained in toothpastes
      and mouthrinses. PURPOSE: The aim of the study was to assess the effect of
      mouthrinses containing chlorhexidine digluconate on the activity of cathepsin C
      in human saliva. MATERIAL AND METHODS: Material for analyses contained mixed
      saliva samples collected at rest, directly into test tubes (Z PS type, Medlab) at
      least 2 hours after meal from 40 subjects (dentistry students; 30 women and 10
      men), aged 19-24. Saliva was collected before the preparations were applied after
      rinsing the mouth with distilled water and following a single use of the
      preparations according to the producer's instructions, 8 samples for each
      preparation. RESULTS: The decrease of cathepsin C was observed for each
      preparation, but was the greatest after mouth rinsing with Kin Gingival (65.08%)
      and Corsodyl (58.00%). CONCLUSIONS: The current study confirms this assumption by
      finding a decrease in cathepsin C activity after the use of chlorhexidine mouth
      rinses.

PMID- 17458069
TI  - Assessment of dental status and oral hygiene in the study population of cystic
      fibrosis patients in the Podlasie province.
AB  - PURPOSE: Cystic fibrosis (CF) is one of the most common genetic diseases
      worldwide. It is caused by mutations of the gene situated on the long-arm of the
      7th chromosome coding Cystic Fibrosis Transmembrane Conductance Regulator (CFTCR)
      which is responsible for the synthesis of cAMP-dependent membrane chloride
      channel located on the top surface of epithelial cells of exocrine glands.
      Accumulation of the secretion in the outlet ducts caused by a dysfunction or lack
      of CFTR proteins leads to abnormal activity of exocrine glands, especially in the
      respiratory and alimentary tracts. Carbohydrates, the main dietary component,
      supply energy to the body, but at the same time are the major cariogenic agent.
      The aim of the current study was to assess dental caries disease and oral hygiene
      in CF patients in the region of Podlasie. MATERIAL AND METHODS: The study
      involved 23 patients with cystic fibrosis, aged 2.5-24 years, from the Podlasie
      Province treated in the Outpatient Cystic Fibrosis Department of the Children's
      University Hospital in Bialystok. Three age groups were distinguished: 1-5, 6-12,
      13-24 years. The following were evaluated: caries incidence (percentage of
      patients with caries CI), caries intensity--based on the mean dmf/DMF score, oral
      hygiene--based on the dental plaque index (OHI-pl). RESULTS: The incidence rate
      of caries was found to be very high both in the CF population and in the control
      group. In children with mixed dentition it was 100%. For permanent teeth, mean
      DMF score was 3.55 in group II and 10.9 in group III. In CF patients, dental
      plaque index was the highest in group III. CONCLUSIONS: In CF patients, there is
      a serious risk of caries due to severe course of the disease, long-term
      administration of medications and high carbohydrate diet. CF patients should
      remain under constant dental care according to the individually designed
      programmes of oral health promotion and caries prophylaxis.

PMID- 17458070
TI  - Assessment of dentition status and oral hygiene in first year dental students,
      Medical University of Bialystok.
AB  - PURPOSE: Caries, a social ailment, is one of the diseases of civilization of the
      20th century. In Poland, the incidence rate of caries is very high both in the
      young and adults. The major etiological factors of caries are: improper oral
      hygiene, diet based on carbohydrate-rich and highly processed food products,
      neglect of prophylaxis and dental check-up. The aim of the study was to assess
      dental status and oral hygiene of the first year dental students, Medical
      University of Bialystok, through the analysis of the chosen caries and dental
      plaque indices. MATERIAL AND METHODS: The study group consisted of 70 first year
      dentistry students, including 50 women and 20 men, aged 19-23 years. Dentition
      status and oral hygiene were assessed using basic dental instruments, in
      artificial light, in clinical settings of the Department of Social Dentistry and
      Prophylaxis, Medical University of Bialystok. RESULTS AND CONCLUSIONS: The record
      analysis showed a very high caries frequency index and a low treatment index.
      However, proper oral hygiene was observed, which may indicate greater health
      promoting awareness among future dentists. Poor dentition status found in the
      study group of dental students may be due to neglect of oral hygiene, prophylaxis
      and lack of systematic dental control in the earlier age periods.

PMID- 17458071
TI  - Prosthetic status and needs of HIV positive subjects.
AB  - PURPOSE: The aim of this study is an evaluation of existing dentition
      reconstructions in HIV-infected patients and definition of prosthetic needs of
      the examined population. MATERIAL AND METHODS: We examined 49 HIV-infected
      subjects (19-52 years of age) and 49 non-infected patients as the control group.
      Dental services were evaluated using treatment structure. The analysis of teeth
      loss was performed by using index created by Rogowiec. The area of prosthetic
      treatment was also defined. Aquired data were analyzed in examined populations
      regarding infection's duration time. RESULTS: Analysis of Rogowiec index values
      showed heavy losses in all anatomic groups of teeth and treatment structure index
      in the group of HIV infected subjects reached value 71.27%. The percentage of
      infected patients using prosthetic dentures was two times higher than in control
      group. In mandible, this difference was more significant. As the HIV infection's
      duration time increased, the percentage of subjets with prosthetic dentures in
      both dental arches also increased. Reconstruction of maxilla's dentition was
      necessary in 38.78% of HIV(+) subjects. In infected group, the necessity of
      reconstruction of teeth loss in lower dental arch reached 46.94%. As the
      infection's duration time increased, prosthetic needs of upper dental arch
      slightly decreased and needs of lower dental arch increased. CONCLUSIONS: 1.
      Using only emergency dental aid by HIV infected people results in significant
      loss of dentitnion. 2. Extraction domination over conservative reconstrucions in
      dental treatment, despite of young age of examined subjests, leads to damage of
      mastication organ. 3. The teeth loss in subjects infected for a longer period of
      time, results in increased need of prosthetic treatment.

PMID- 17458072
TI  - Periodontal status and treatment needs in HIV-infected patients.
AB  - PURPOSE: The aim of this study is evaluation of periodontal status and definition
      of periodontal treatment needs in HIV infected patients. MATERIAL AND METHODS: We
      examined 49 HIV-infected subjects (19-52 years of age) and 49 non-infected
      patients as the control group. Periodontal status and treatment needs were
      evaluated by using CPITN - Community Periodontal Index and Treatment Needs.
      Aquired data were analyzed in examined populations regarding infection's duration
      time and in dependance on absolute number of CD4 lymphocytes in microl of plasma,
      dividing patients according to criterion of HIV infection classification after
      CDC (Centers for Diseases Control and Prevention). RESULTS: More advanced changes
      in the paradontium were observed mostly in examined HIV infected subjets. As HIV
      infection time proceeds, the periodontal status of examined patients impairs,
      what is manifested by the decrease of the number of sextants with the intact
      paradontium and the increase of the number of sextants excluded from the
      research. There was no significant relation found between periodontal status
      evaluated with CPITN and the immunity status of examined subjects. 26.5% of HIV
      infected subjects needed the complex therapy. As the immunity decreased, the
      number of patients qualified to the complex treatment increased, and the number
      of HIV(+) patients with no need of therapy decreased. CONCLUSIONS: 1. As the
      infection duration time proceeds, the periodontal status in HIV-infected patients
      impairs. 2. Deterioration of health status, expreesed with decrease of absolute
      number of CD4 lymphocytes is accompanied by intensification of pathological
      periodontal changes. 3. HIV infected persons are group with high periodontal
      needs and require intensive periodontal care.

PMID- 17458073
TI  - Comparative analysis of the effect of preparations used in professional fluoride
      prophylaxis on the chosen parameters of human saliva.
AB  - Regular supply of fluoride ions to the oral environment is one of the
      prophylactic actions against dental caries. Fluorides, whose exogenous action
      combines with saliva properties, condition the anticariogenic effect. Fluoride
      ions exhibit high chemical activity, can alter the oral environment parameters
      and inhibit the activity of enzymes. PURPOSE: In the current study, the effect of
      fluoride preparations used in professional caries prophylaxis on chosen saliva
      parameters was studied. The levels of pH and fluoride ions, and the activity of
      cathepsin D in human saliva were determined. MATERIAL AND METHODS: Material for
      analysis contained resting mixed saliva collected before and 1, 4 and 24 hours
      after the application of Duraphat, Elmex Gel, Fluor Protector, Fluormex Gel and
      Fluoro-Gel. RESULTS: The fluoride-containing preparations inhibited the activity
      of cathepsin D in the way depending on the time that had passed since the
      application and altered the pH level of human saliva.

PMID- 17458074
TI  - Students' knowledge of oral hygiene vs its use in practice.
AB  - PURPOSE: The purpose of the work is to estimate the knowledge connected with the
      rules of the oral hygiene and its correlation with everyday habits among the
      students of Dental studies and Medical Studies at Medical School in Lublin and
      Polytechnics of Lublin. MATERIAL AND METHODS: A survey was conducted among 483
      students: 58 2nd-year and 88 5th-year students of dentistry, 97 2nd-year and 51
      5th-year students of medicine and 108 2nd-year and 81 5th-year students from The
      Polytechnics of Lublin. RESULTS: The study revealed that 50% students of
      dentistry, 32.43% students of medicine and 26.6% students of polytechnics brush
      their teeth after every meal; 94.23% students of dentistry, 89.91% students of
      medicine and 78.8% students of polytechnics know-how often teeth should be
      brushed. Students had better knowledge of how frequent they should change a
      toothbrush: 71.8% students of dentistry, 61.49% students of medicine and 54.4%
      students of polytechnics change their toothbrushes every 3 months, however,
      84.61%, 62.16% and 49.42% students respectively have knowledge concerning the
      frequency of changing a toothbrush. The study also revealed that 13.46% students
      of dentistry, 10.14% students of medicine and 6.49% students of polytechnics
      visit dental clinic every 3 months, however, 4.49%, 13.51% and 14.05% students
      respectively go to see the dentist less than once a year. The reason for making a
      dental appointment was pain in 7.05% students of dentistry, 16.22% students of
      medicine and 22.22% students of polytechnics and a check-up in 64.74%, 62.84% and
      51.85% students respectively. CONCLUSIONS: Students' knowledge of oral hygiene
      does not always correlate with practice.

PMID- 17458075
TI  - Evaluation of the results of periodontal treatment by means of digital
      subtraction of radiographic images.
AB  - This article presents general principles and a sample case of application of
      digital subtraction of x-rays for objective evaluation of results of treatment in
      dentistry. PURPOSE: Evaluation of the results of surgical periodontal treatment
      by means of digital subtraction of radiographic images taken before and 12 month
      after surgery. MATERIAL AND METHODS: For evaluation of the results of guided
      tissue regeneration treatment of deep bony defects digital periapical x-rays were
      taken before and 12 months after surgery. Pairs of images obtained during
      treatment were calibrated to equalize vertical x-ray beam angulation followed by
      calibration to radiological contrast and density. Next the comparison of images
      taken before and after treatment was performed by means of special computer
      software designed to subtract content of given images. RESULTS: Digital
      subtraction showed that the radiological density in regions where surgery was
      performed has decreased over a period of 12 months meaning that the mineral
      content which is responsible for absorbing x-ray photons has increased. Some
      local foci of subsurface hypomineralization were found on subtractions images.
      These foci couldn't be detected clinically because hypomineralization was taken
      place within bone. CONCLUSIONS: Digital subtraction of x-rays taken before and
      after surgery treatment is detailed and objective method of evaluating results
      particularly when changes of surface and subsurface bone mineralization around
      teeth must be examined.

PMID- 17458076
TI  - The relationship between mineral status of the organism and the number of teeth
      present and periodontal condition in postmenopausal patients.
AB  - PURPOSE: The determination of the relationship between the mineral status of the
      organism and the number of teeth present and periodontal condition in women after
      menopause. MATERIAL AND METHODS: The study covered 65 postmenopausal women with
      partial loss of dentition, mean age was 66.2 years. The group was divided into 3
      subgroups: healthy, with osteopenia and with osteoporosis. The division was made
      on the basis of the results of densitometric analysis (BMD) of femoral neck (F)
      and the lumbar spine (L2-L4), according to diagnostic criteria concerning the
      density of bone mass according to WHO. The number of teeth present was taken into
      consideration in the clinical examination. Periodontal condition was evaluated
      using CPITN index. RESULTS: The total number of own teeth strongly negatively
      correlated with the results of the lumbar spine densitometry. The correlation
      between mineral density of the lumbar spine and the femoral neck and the number
      of teeth in the maxilla was also strongly negative. However, the significant
      relationship between the number of teeth present in the mandible and the mineral
      density of examined bones was not observed. We did not state the increase in
      periodontal changes advancement together with the decrease in mineral status in
      the examined group of women. CONCLUSIONS: There was not any influence observed of
      the decreased mineral status of the organism on the number of own teeth and the
      degree of periodontal disease advancement.

PMID- 17458077
TI  - Evaluation of periodontal status in young patients with insulin-dependent
      diabetes mellitus (type 1).
AB  - PURPOSE: The aim of the study was to value periodontal status in young persons
      with well-controlled insulin-dependent diabetes mellitus (IDDM). MATERIAL AND
      METHODS: We examined 50 young people with IDDM (25 girls and 25 boys) and 50
      healthy subjects (25 girls and 25 boys). Mean age of examined persons was about
      14 years. We investigated gingival indexes: GI (Gingival Index) and PBI
      (Papillary Bleeding Index) and periodontal indexes: PI (Periodontal Index) and
      PDI (Periodontal Disease Index). The results were statistically analysed, and
      significant differences we observed for p < 0.05. RESULTS: The mean scores of
      Gingival Index and Papillary Bleeding Index were lower in healthy subjects but
      differences were not statistically significant. Only maximum scores of these
      indexes were significantly higher in diabetics. The mean and maximum values of
      Periodontal Index were significantly higher in patients with IDDM. We did not
      notice differences between mean scores of PDI in both examined groups. Analysis
      of maximum values of Periodontal Disease Index reveals higher level in diabetic
      girls than in female controls. CONCLUSIONS: IDDM patients may be at risk of
      periodontal diseases. Well-controlling insulin-dependent diabetes mellitus may be
      important for periodontal tissues status and prophylaxis of periodontal diseases.

PMID- 17458078
TI  - The effect of glass ionomer cement Fuji IX on the hard tissues of teeth treated
      by sparing methods (ART and CMCR).
AB  - PURPOSE: The aim of the study was to assess the effect of glass ionomer fillings
      Fuji IX on the mineral content of the hard dental tissues of carious teeth
      treated by sparing methods. MATERIAL AND METHODS: The study material consisted of
      4 deciduous teeth lost due to physiological resorption. The teeth had glass
      ionomer fillings Fuji IX inserted after treatment of caries by means of sparing
      methods (ART and CMCR). Chemical analysis of enamel and dentin was performed by
      means of energy dispersive spectroscopy (EDS) with X-ray analysis QUEST system at
      a distance of 20 um (point C) and 120 um (point D), respectively. The content of
      the following elements was evaluated in weight percent: oxygen (O), fluoride (F),
      sodium (Na), magnesium (Mg), aluminum (Al), silicon (Si), phosphorus (P), calcium
      (Ca), strontium (Sr). The Ca/P ratio was calculated. T-student test for pairs,
      with the level of significance p < 0.05, was used for statistical analysis of the
      results. RESULTS: We found significantly higher levels of fluoride, aluminum and
      silicon and lower concentrations of calcium and phosphorus in the dentine
      adjacent to the filling (point C). However, no statistically significant
      differences were observed in the levels of the elements between these two sites
      of measurement. CONCLUSIONS: Our results indicate that mineralization of the
      calcified dentine may involve elements released from glass ionomer cement Fuji
      IX.

PMID- 17458079
TI  - Tobacco smoking problem in a group of 18-year-old high school students in the
      city of Gdansk--finding causes and preventive methods.
AB  - PURPOSE: The aim of the study was to evaluate smoking prevalence among 18-year
      old secondary school students as well as their awareness of systemic health
      threats of smoking. Our goal was also to discuss the youth smoking risk factors
      and effective ways both to prevent and fight smoking problem. MATERIAL AND
      METHODS: 1516 18-year-old students (808 men, 708 women) from randomly selected 12
      high schools were studied. The adolescents fulfilled the anonymus questionaire.
      RESULTS: 34.1% (517) of all participants smoke every day or occasionally, with
      the highest percentage of smokers in vocational schools (49.6%); women are the
      most frequent smokers (52.8%). The lower prevalence of smoking was observed in
      high schools (21.2% of men, 20% of women). In technical high schools 36.1% of men
      and 11.1% of women were smokers. The habitual smokers were found in all schools;
      the highest percentage was observed in vocational schools (32.75%-33.13%). The
      percentage was particularly high among women (33.13%). 92.09% of studied women
      and 89.95% of men were aware of smoking systemic health threats (93.84% of high
      school students, 88.25% of vocational school students). CONCLUSIONS: It is
      alarming that the percentage of smokers among 18-year-old students is high, in
      particular among women and vocational schools students. The results indicate that
      smoking is a serious problem in this population. It is vital to create the
      preventing and educating programmes addressed especially to adolescents. There is
      a need of future studies aimed to evaluate smoking risk factors and create
      effective methods of prevention as well as smoking cessation help resources.

PMID- 17458080
TI  - Bone structure regeneration after low induction magnetic field treatment in teeth
      chosen for extraction.
AB  - PURPOSE: The aim of the work was to use and to evaluate the usefulness of the
      slow variable magnetic fields to aid the treatment of the teeth chosen for
      extraction. The marginal paradontium of periapical bone of teeth was in a state
      of extensive destruction. The teeth were chosen for extraction. MATERIAL AND
      METHODS: 13 patients were chosen. 10 of them had with endo-perio changes and 3
      suffered from full tooth luxation and had the teeth replanted. Those people were
      to have an extraction procedure or were declared as impossible to treat in other
      dental offices. Patients underwent non-aggressive skaling, endodontic treatment
      and were exposed to slow variable magnetic fields generated by Viofor JPS,
      accordingly to methods and parameters suggested by Department of Propaedeutics in
      Dentistry of Pomeranian Medical University in Szczecin. The process of healing of
      changes was evaluated radiologically. RESULTS: RTG done after 2 weeks and after 2
      months were evaluated in respect of bone regeneration. They show the bone
      structure concentration. A RTG evaluation after half a year, two and three years
      show a preservation of the bone structure concentration. CONCLUSIONS: The use of
      slow variable magnetic fields contributed to bone structure regeneration and to
      preserve teeth with recorded endo-perio syndrome. Endodontic treatment of
      replanted teeth, aided with magnetostimulation has stopped the osteolisis
      process.

PMID- 17458081
TI  - New technology in endodontics--the Resilon-Epiphany system for obturation of root
      canals.
AB  - PURPOSE: Clinical and laboratory assessment of a new root canal filling material-
      Resilon-Epiphany system. MATERIAL AND METHODS: In 21 patients, 48 root canals
      were filled using a single-cone method or lateral condensation technique of gutta
      percha with addition of Epiphany sealer. Laboratory investigations were performed
      on 4 extracted one-root human teeth, which were prepared by means of a crown-down
      technique and obturated with Resilon-Epiphany using System B and Obtura II. Next,
      the roots were transversely cross-sectioned in the mid-length at a 2 mm distance
      from the apex and analysed in SEM. RESULTS: After a year, the treatment proved to
      be clinically and radiologically successful in all the patients. SEM analyses
      revealed good adhesion of Epiphany sealer to the canal walls with visible tags in
      dentine tubules. Good adherence was also found of Epiphany to Resilon and Resilon
      to root dentine, but few gaps were also observed. CONCLUSIONS: Our preliminary
      positive results require more thorough evaluation, longer observation period and
      a larger group of patients. However, they allow the assumption that resin-percha
      will successfully replace gutta-percha in the nearest future.

PMID- 17458082
TI  - Assessment of salivary levels of the chosen exoglycosidases in patients with
      aggressive periodontitis after treatment with doxycycline.
AB  - PURPOSE: The aim of the study was the clinical assessment of the periodontium in
      patients with aggressive periodontitis (AP) after treatment with doxycycline
      hyclate. Moreover, an attempt was made to evaluate the effect of the treatment on
      the salivary concentrations of beta-glucuronidase, HEX, HEX A and HEX B in AP
      patients. MATERIAL AND METHODS: Sixteen patients with aggressive periodontitis,
      aged 28-45 years, were enrolled in the study. The patients were treated with a
      doxycycline hyclate preparation (Periostat) for 2 months at a dose of 20 mg twice
      a day. The clinical examination was performed twice, directly prior to
      pharmacological treatment and after its termination. The following clinical
      parameters were evaluated: the plaque index (PI), the sulcus bleeding index
      (SBI), the pocket probing depth (PPD) and the clinical attachment level (CAL).
      Biochemical determination of beta-glucuronidase, HEX, HEX A and HEX B
      concentrations in non-stimulated saliva was performed before and after treatment.
      RESULTS: In AP patients, the values of PI, SBI and CAL before and after treatment
      were comparable. The mean pocket probing depth before treatment was 3.5 mm, which
      decreased significantly after treatment (3.2 mm). The values expressed as pKat/kg
      protein for specific enzymatic activities of HEX, HEX A, HEX B and beta
      glucuronidase in the saliva of AP patients before and after doxycycline treatment
      were similar. CONCLUSIONS: A 2-month treatment with doxycycline is too short to
      obtain clinical changes. Although the assessment of the activity of such enzymes
      as beta-glucuronidase, HEX, HEX A and HEX B in the saliva of AP patients allows
      detection of periodontal inflammation, it cannot be used to determine the risk of
      its development and therefore has no practical significance.

PMID- 17458083
TI  - Efficacy of local treatment with chlorhexidine gluconate drugs on the clinical
      status of periodontium in chronic periodontitis patients.
AB  - PURPOSE: Chlorhexidine gluconate is a relatively commonly used chemotherapeutic
      in the treatment of periodontitis (P), exhibiting antimicrobial capabilities
      against Gram-negative and Gram-positive bacteria, and fungi. This compound is a
      component of various preparations for topical use in the form of solutions for
      mouthrinsing or peri-irrigation, gels, varnishes, chips and even chewing gums.
      The aim of the study was the clinical evaluation of periodontium after treatment
      with one of the drugs containing chlorhexidine gluconate (Corsodyl) as compared
      to professional tooth cleaning in patients with chronic periodontitis. MATERAL
      AND METHODS: Forty subjects enrolled in the study were divided into four groups,
      10 in each group, according to the mode of treatment (Corsodyl rinse, Corsodyl
      gel, Corsodyl gel + surgical dressing, scaling). RESULTS: The greatest
      differences between baseline and follow-up examinations were observed in the
      group where surgical dressing was applied in addition to Corsodyl gel and in the
      group treated with scaling. CONCLUSIONS: Chlorhexidine gluconate should be more
      frequently used as a drug adjunct to classic periodontal therapy, especially in
      the forms allowing its direct application to the periodontal pockets.

PMID- 17458084
TI  - Evaluation of mCD14 expression on monocytes and the blood level of sCD14 in
      patients with generalized aggressive periodontitis.
AB  - PURPOSE: Lipopolysaccharides (LPS), a major component of the cell membrane of
      gram-negative bacteria, are the main stimulants of the host immune response,
      initiating inflammatory changes and responsible for periodontal tissue
      destruction. The mCD14, which is found primarily on monocytes and macrophages, is
      the key membranous receptor involved in LPS binding. CD14 is also present in the
      serum as a soluble form (sCD14) released due to shedding from monocytes. The aim
      of the study was to assess CD14 expression on peripheral blood monocytes in
      patients with generalized aggressive periodontitis (GAP). The level of sCD14 was
      also determined in the serum of GAP patients. MATERIAL AND METHODS: The study
      group consisted of 16 patients with generalized aggressive periodontitis, the
      control group had 13 systemically and periodontally healthy subjects. The
      expression of mCD14 was determined by flow cytometry and expressed as mean
      intensity of fluorescence (MIF). Serum sCD14 level was examined with ELISA
      method. RESULTS: The expressions of mCD14 on monocytes in GAP patients and
      control subjects were comparable. No statistically significant differences were
      noted in the mean serum sCD14 level between GAP and control subjects.
      CONCLUSIONS: As periodontitis is a local disorder affecting a small fragment of
      the oral cavity it seems likely that chronic bacterial infection existing there
      is not reflected in the peripheral parameters.

PMID- 17458085
TI  - The assessment of periodontium in patients with uncontrolled diabetes.
AB  - PURPOSE: Uncontrolled diabetes leads to disturbances of carbohydrate, protein,
      and lipid balance as well as morphological changes in many organs. It can be
      assumed that the changes can also regard the masticatory organ and thus,
      periodontal tissues. The aim of the study was the assessment of periodontium in
      patients with uncontrolled diabetes (HbA1c > 7%) and the comparison of the
      results with data obtained in the group of healthy individuals--depending on sex.
      MATERIAL AND METHODS: The study was carried out in the group of 275 subjects: 155
      hospitalized patients with uncontrolled diabetes (the examined group) and 120
      healthy individuals comprising the control group. Russell's index was used for
      the evaluation of the periodontal condition. RESULTS: The mean level of glycated
      hemoglobin HbA1c in patients was 9.43% in women and 9.57% in men. The mean value
      of Russell's index was 2.14 in the examined group and 0.99--in the controls. The
      difference was statistically significant (p < 0.001). DISCUSSION: Although other
      authors' results are ambiguous and controversial, the theory that there is the
      connection between uncontrolled diabetes and periodontitis and the consequences
      of the coexistence of these diseases are very serious, is still maintained.
      CONCLUSIONS: Uncontrolled diabetes was the crucial cause of periodontal changes
      and, to a large extent, influenced the function of the masticatory organ in
      patients.

PMID- 17458086
TI  - Multidisciplinary treatment of patients after a surgery due to cancers in the
      facial area: a clinical reports.
AB  - Prosthetic rehabilitation of patients after surgical removal of carcinoma in the
      facial skeleton is one of the most difficult problems in therapy of the
      stomatognathic system, due to increasing incidence of head and neck carcinoma.
      Significant deformations of tissues, development of dysfunctions of the
      stomatognathic system with concurrent biological unbalance of the oral cavity
      enviroment are frequently a consequence of the treatment. Cicatricial scars,
      contraction of the oral crevice and limitation of mobility of the tongue are
      noted in numerous cases. Deformations of the facial area of the skull and of
      structures of the temporo-mandibular joint are also the reasons of occlusion and
      articulation disturbances. Two cases of surgery due to carcinoma in the facial
      skeleton that have required combined and stepwise multispecialistic treatment
      performed at Department of Prosthetic Dentistry and Department of Periodontology
      and Oral Disease, Dental Institute, Medical University of Warsaw are presented.
      The therapy has involved treatment of periodontitis and applying appropriate
      construction of prostheses that would relieve periodontium and splinting teeth.

PMID- 17458087
TI  - The choice of conditions for cathepsin D activity determination in human saliva.
AB  - The aim of the study was the demonstration and choice of conditions for the
      determination of cathepsin D activity in human mixed saliva. The 6% solution of
      hemoglobin, denatured with hydrochloric acid, was used as the substrate. The
      ratio of saliva volume to hemoglobin was 4:1 w/v. The reaction was interrupted by
      adding 10% trichloroacetic acid, after 6 hours of incubation at 37 degrees C. The
      increase in degradation products was determined with the use of Folina and
      Ciocalteau method with copper modification.

PMID- 17458088
TI  - Bacterial composition in the supragingival plaques of children with and without
      dental caries.
AB  - PURPOSE: The purpose of the present investigation was to determine if the
      supragingival bacterial composition plaques in children with caries would differ
      from those found in caries-free controls. MATERIAL AND METHODS: Pooled
      supragingival plaque samples from the smooth surfaces of teeth were collected
      from 75 children with caries and 131 children without caries. The plaque samples
      were analysed for bacterial content by cultures on a series of non-selective and
      selective media for aerobic, microaerophilic and anaerobic bacteria.
      Additionally, the specimens of dentine carious lesions were examined. The
      standard culture procedures and identifications of bacteria were used. RESULTS:
      Among 131 children without dental caries, 41 (31.3%) were at preschool age with
      deciduous teeth and 90 (68.7%) at school age with permanent teeth. Dental plaques
      of caries-free children revealed 452 strains, out of which 326 (72.1%) were from
      permanent teeth, 126 (27.9%)--from deciduous teeth (p = 0.0001). Among 75
      children with dental caries, 61 (81.3%) were at preschool age and 14 (18.7%)--at
      school age. There were 239 strains isolated from supragingival plaques in
      children with dental caries, 187 (78.2%) --in preschool children, and 52 (21.8%)-
      in school children (p < 0.05). From dentine carious lesions in these children,
      209 strains were isolated; 164 from preschool children and 45--from school
      children (p < 0.05). Gram-positive bacteria were isolated more frequently than
      Gram-negative ones (p = 0.0001) from supragingival plaques both in children with
      and without dental caries. Streptococcus genus bacteria were isolated more often
      (p = 0.0002) from the plaques in school children without dental caries. The
      proportion (%) of aerobic and anaerobic bacteria was comparable (p > 0.05) in
      dental plaques in children with and without dental caries, except for Veillonella
      spp., which were isolated more frequently from dental plaques in school children
      with dental caries (p = 0.01). CONCLUSIONS: 1) Generally, there was no
      statistically significant difference of bacterial species composition isolated
      from supragingival plaques in children with deciduous and permanent dental caries
      and caries-free children. 2) There was no difference between bacterial
      composition in dentine carious lesions of deciduous teeth and permanent teeth as
      compared to supragingival plaques in these children (except for Neisseria spp.,
      Peptostreptococcus spp.).

PMID- 17458089
TI  - Oral Candida albicans carriage in healthy preschool and school children.
AB  - PURPOSE: The purpose of the present study was to detect Candida albicans carriage
      in the oral cavity of healthy preschool and school children. The second aim was
      the determination of correlation between C. albicans occurrence and dental caries
      in children population. MATERIAL AND METHODS: The samples for mycological
      examinations were collected from the pharynx and supragingival plaque, and
      carious lesions in 102 children, aged 4-7 years (preschool children) and 104
      children and adolescents, aged 12 and 18 (school children). All samples were
      cultured directly on Sabouraud agar medium. Isolated yeasts were identified based
      on API 20C AUX (bioMerieux). RESULTS: A total of 123 C. albicans strains were
      isolated, in which 61 (49.6%) derived from supragingival plaque, 48 (39%)--from
      carious lesions, and 14 (11.4%)--from pharyngeal swabs. C. albicans was isolated
      from the samples of single material in 61 children (35--school children, 26 -
      preschool children) while from the rest of 29 children, C. albicans was isolated
      from two (25x) or three materials (4x). C. albicans was detected in 48/75 (64%)
      children with dental caries; the rate was statistically significantly higher as
      compared to the overall number of children with C. albicans carriage (90/206;
      43.7%) (p = 0.0026). Similar results was obtained in preschool children (38/61;
      62.3% and 47/102; 46.1%, respectively) (p = 0.0449), as in school children
      (10/14; 71.4% and 43/104; 41.3%, respectively) (p = 0.0336). CONCLUSIONS: 1)
      Candida albicans was observed in the oral cavity of healthy children with high
      (approximately 40%)--comparable rate in school and preschool children (p > 0.05).
      2) C. albicans was isolated with high comparable rate from carious lesions in
      preschool and school children. The statistically significant differences between
      the rate of C. albicans in carious lesions in preschool children (62.3%) and
      school children (71.4%) and the overall number of children with C. albicans
      carriage in the oral cavity of children in both age groups (p < 0.05) were
      showed.

PMID- 17458090
TI  - The relationship between masticatory efficiency and the state of dentition at
      patients with non rehabilitated partial lost of teeth.
AB  - Factors believed to affect masticatory efficiency include loss of postcanine
      teeth, bite force, severity of malocclusion, occlusal contact area, body size and
      oral motor function. THE AIM: to record if there is relationship between
      masticatory efficiency and the state of dentition at patients whose occlusion has
      never been rehabilitated. MATERIAL: The study was performed in 22 patients who
      were missing over 50% of their functional dental units and never used any
      prosthetic appliances and in 15 healthy completely dentate controls. METHODS: The
      masticatory efficiency was measured using Optosil test for 20 and 80 cycles of
      chewing. The occlusal conditions were analyzed by means of the computerized T
      Scan II System which registered the maximal force of pressure during the maximal
      occlusal contacts, the time which passed between the first contact and the
      maximal force of pressure and the occlusal platform area. RESULTS: It was
      observed a considerable difference in the integrity of the masticatory system
      between both groups. The force of pressure on the indicator, chewing platform
      area and the time from the first contact to the maximal force calculated in T
      Scan II System differs significantly between both groups. The value of X50 for 20
      and 80 cycles of chewing estimated in Optosil test were statistically significant
      only for 80 cycles of chewing. CONCLUSION: The severe reduction of the number of
      functional dental units is caused of the impairment of chewing ability but
      prolongation of mastication could improve the comminution of hard food.

PMID- 17458091
TI  - Assessment of periodontal status following the alignment of impacted permanent
      maxillary canine teeth.
AB  - PURPOSE: The aim of the study was to assess the effect of orthodontic movement of
      the impacted canines after surgical exposure and alignment on the periodontal
      status of the transpositioned and adjacent teeth as well as to compare certain
      parameters with those of spontaneously erupted teeth. MATERIAL AND METHODS:
      Twenty-four patients (mean age 18.4 +/- 3.66) with unilaterally impacted 24
      canines were enrolled in the study. The following parameters were assessed:
      pocket depth (PD), clinical attachment level (CAL), platelet index (PI) of
      Silness and Loe, and modified sulcus bleeding index (SBI). Optic density of the
      alveolar bone along the root surface of the aligned canine was analysed based on
      digital radiological images made with the right angle technique. Control group
      consisted of spontaneously erupted teeth. RESULTS: In comparison to the control
      group, in the orthodonticaly treated group PD was found to increase on the mesial
      buccal and palatal surfaces of the first premolar (p < 0.003, p < 0.04), on the
      treated side; on the distal buccal (p < 0.01), mesial buccal (p < 0.0005), mesial
      palatal (p < 0.02) and distal palatal surfaces of the canine (p < 0.02); and on
      the distal buccal (p < 0.04) and distal palatal surfaces of the lateral incisor
      (p < 0.048). CAL was statistically significant on the mesio-buccal and mesio
      palatal surfaces of the aligned canine (p < 0.02). PI was statistically
      insignificant, while SBI values at the aligned tooth were statistically
      significant (p < 0.0004). Positive correlation was found between treatment
      duration and distance to the occlusal plane (d) expressed by the correlation
      coefficient r = 0.49 (p < 0.02). No relationship was observed between bone
      density within the canine alignment zone and the control, and there was no link
      between the method of treatment and periodontal status, either. CONCLUSIONS: The
      alignment of the impacted permanent maxillary canines poses a risk of periodontal
      deterioration. Patients subjected to surgical-orthodontic treatment require
      periodic periodontal follow-ups.

PMID- 17458092
TI  - Oral cavity status and IgE level in orthodontic patients.
AB  - PURPOSE: Considering nickel release from fixed orthodontic appliances,
      determination of the relationship between the clinical status of the mouth, IgE
      level and treatment duration in orthodontic patients seems to be advisable.
      MATERIAL AND METHODS: Twenty-one patients with symptoms of nickel
      hypersensitivity observed during treatment with fixed orthodontic appliances were
      separated from a group of 50 subjects, aged 11-33 years, undergoing orthodontic
      treatment for malocclusion. The patients were divided into two subgroups PgA and
      PgB. RESULTS: The mean IgE level in PgA was 39.20 IU/ml and in PgB 210.61 IU/ml.
      In PgA, the majority of patients were wearing ear-rings (8/10), but not in PgB
      (4/11). The mean treatment duration in PgA was 21.3 +/- 4.83 months, while in PgB
      14.4 +/- 2.84. There were no statistically significant differences in the
      symptoms indicating stomatitis between the groups of patients subjected to
      treatment with intra-oral appliances. CONCLUSIONS: The immunologic profile of the
      patient plays a key role in the choice of the type of appliance used to treat
      abnormalities of the masticatory organ. Determination of IgE is necessary in the
      case of allergy-positive history.

PMID- 17458093
TI  - Recession occurrence in patients treated with fixed appliances--preliminary
      report.
AB  - PURPOSE: The aim of the study was to evaluate the dependence of gingival
      recession, malocclusion and factors that may lead to recessions of the gingiva in
      patients applying for orthodontical treatment. MATERIAL AND METHODS: The study
      involved 52 randomly selected patients treated with fixed appliances due to
      occlusal irregularities and dental abnormalities. Data obtained from the
      examination and selected parameters from cephalometric analysis were placed in a
      chart including ANB skeletal class and Wits parameter, lower incisor position
      IMPA, dental abnormalities, extractions due to orthodontical indications and
      recession etiopathic factors. Statistical analysis of obtained data was conducted
      using variance analysis. Statistically significant were assumed those
      calculations for which value of significance level p < or = 0.05. RESULTS:
      Recession was observed in 18 patients of the 52 examined. Skeletal I class was
      found in 11 patients (61.12%) and in 8 cases Wits parameter corresponded with
      skeletal class III (44.4%). Among the patients examined normal incisor
      inclination was observed in 6 patients (33.33%), whereas 12 cases revealed
      inclination irregularities (66.66%). Clinical examination disclosed dental
      defects in 13 patients (72.22%) and in 12 cases recession etiopathic factors were
      recognized (66.66%). Statistically significant differences between periodontal
      biotype and gingival recession of 43, 31, 33 teeth were estimated. CONCLUSIONS:
      Anatomical factors, malocclusion and dental irregularities were fund to be the
      main cause of the single and/or multiple recessions. Patients applying for
      orthodontic treatment due to occlusal abnormalities should remain under
      particular control in case of symptoms suggesting the incidence of recession,
      particularly when recessions are already present.

PMID- 17458094
TI  - Complications in the course of surgical-orthodontic treatment of impacted
      maxillary canines.
AB  - PURPOSE: The purpose of the study was to assess the effect of gender and age of
      patients with impacted permanent maxillary canines on complications in the course
      of tooth transposition. MATERIAL AND METHODS: The study material included files
      of 82 patients with a diagnosis of unilateral or bilateral impaction of 102
      permanent maxillary canines. The study group consisted of 65 female and 17 male
      subjects, aged 8.5-39 years (mean 14.5 years) divided into four age groups: group
      I--patients under 12, group II--12.0-13.9 years, group III--14.0-15.9 years and
      group IV--patients at the age of 16 and older. RESULTS: In the study population,
      the impacted teeth showed the following locations: palatal (67.64%), vestibular
      (19.60%) and alveolar (12.74%). Spontaneous resorption caused by abnormal tooth
      position was observed in 5 (4.9%) permanent maxillary lateral incisors. In 4
      cases, the resorption was bilateral and all the five cases were recorded in group
      III. In group IV, one patient had alveolar process atrophy and severe resorption,
      while another one showed ankylosis of a permanent canine. Extraction of palatally
      impacted canines was done in 3.92% of cases. Complications were noted in girls
      and referred to 5.58% of the study cases. CONCLUSIONS: Orthodontic movement of
      the impacted teeth to the dental arch may result in complications. However,
      because of the major significance of the upper canine which is responsible for
      the behaviour of the frontal triad, surgical-orthodontic treatment should be
      undertaken to improve occlusion and the aesthetic look of patients. Thus, any
      case of the ectopic canine requires observation and proper choice of radiological
      diagnostics.

PMID- 17458095
TI  - Tryptophan and its metabolites in patients with oral squamous cell carcinoma:
      preliminary study.
AB  - PURPOSE: It has been showed that tryptophan (TRP) degradation has been linked to
      modulation of cancer cell proliferation. The aim of our study was to estimate the
      concentration of TRP and its derivatives, such as anthranilic (AA) and kynurenic
      acid (KYNA) in plasma, saliva, squamous cell carcinoma (SCC) tissues and healthy
      oral mucosa in patients with oral SCC. MATERIAL AND METHODS: The study was
      performed on plasma, non-stimulated, mixed saliva and squamous cell carcinoma
      tissues and healthy oral mucosa in patients with oral SCC. The concentration of
      TRP and its metabolites were determined by high-performance liquid chromatography
      (HPLC). RESULTS: In plasma the concentration of TRP was 33.73 +/- 2.52 microM, of
      KYNA was 26.97 +/- 5.35 nM and of AA was 32.40 +/- 2.30 nM. In saliva the
      concentration of TRP was 3.81 +/- 0.62 microM, of KYNA was 8.06 +/- 1.86 nM and
      of AA was 20.41 +/- 10.77 nM. In cancer tissues the levels of TRP (30.21 +/- 5.88
      microM), KYNA (15.85 +/- 1 .82 nM) and AA (265.32 +/- 1 51.45 nM) were higher in
      respect to the concentration of TRP (13.28 +/- 0.62 microM), KYNA (12.75 +/- 2.28
      nM) and AA (31.68 +/- 8.89 nM) in normal tissues. The increase in the content of
      TRP, KYNA and AA in cancer tissues reached 127.48 +/- 5.95%, 24.31 +/- 4.35% and
      737.50 +/- 206.96%, respectively. CONCLUSIONS: Our study has demonstrated the
      change of TPR metabolism, which is reflected by the increase TRP, AA and KYNA
      concentrations in patients with oral squamous cell carcinoma. We can suppose that
      these substances may be one of many factors responsible for cancer development.

PMID- 17458096
TI  - The clinical assessment of mobile teeth stabilization with Fibre-Kor.
AB  - PURPOSE: A glass fiber tapes are used in periodontal diseases to stabilize mobile
      teeth. The purpose of this project was to make a clinical appraisal of teeth
      stabilization which were using Fibre-Kor splinting. MATERIAL AND METHOD: 56
      patients 35-67 year old were examined. There were made 162 teeth blocks using
      Fibre-Kor as reinforcement and Flow-It material as matrix. After 10 months
      clinical parameters such as: PI, SBI, GI and periodontal pocket were checked.
      RESULTS: Periodontal pockets depth decreased average by 0.58 mm after teeth
      stabilization. Bleeding index and inflammation of gums fall average by 2.55 and
      1.95. The average oral cavity hygiene improved and achieved 1.46. CONCLUSION: The
      Fibre-Kor splint is an esthetic and functional solution of mobile teeth
      stabilization, and is a part of the specialist periodontal treatment.

PMID- 17458097
TI  - The clinical and radiological assessment of periodontal bone loss treatment using
      Emdogain.
AB  - ADMISSION: Emdogain is the only one biomaterial using biomicra effect which is
      practiced in periodontal surgery. PURPOSE: The purpose of the study was a
      clinical and radiological assessment of bone loss treatment using Emdogain.
      MATERIAL AND METHODS: There were 19 persons examined (11 women and 8 men) which
      have bone loss treated. Initial and monitoring examination after 10 months
      embraced clinical parameters such as PPD, CAL and radiological--based on
      intraoral x-ray pictures. Emdogain treatment was made according to surgical
      procedures. RESULTS: The research has shown reduction of the depth of periodontal
      pockets average about 3.4 mm and attachment connective tissue growth about 2.2
      mm. Bone loss filling was on 67.1% level. DISCUSSION: Bone loss filling and
      growth of connective tissue attachment are in our research lower than in most of
      the others publications. Our observation concerned 10 months period so we should
      expect better effects after longer time. MOTIONS: Emdogain is safe and effective
      regeneration material.

PMID- 17458098
TI  - Activity of lysosomal exoglycosidases in saliva of patients with HIV infection.
AB  - INTRODUCTION: The aim of this work was to evaluate the influence of HIV infection
      on the catabolism of glycoconjugates in oral cavity, by determination the
      activity of lysosomal exoglycosidases in resting whole saliva HIV positive
      patients. MATERIAL AND METHODS: Sample of resting whole saliva from HIV infected
      patients (divided into two groups, depending on lymphocyte CD4+ number in
      peripheral blood) and the control-HIV negative group were analyzed for
      exoglycosidases activity. Determinations the activities (muKat/kg of protein) of
      lysosomal exoglycosidases were performed according to Chatteriee et al., modified
      Zwierz et al. The protein content (mg/ml) was determined by the Lowry method.
      Statistical analysis was performed using packet Statistica 6.0. Results were
      expressed as the mean and SD. P values less than 0.05 were considered
      significant. RESULTS: Exoglycosidases activities were not statistically dependent
      on immunological status of HIV patients. We obtained insignificant increase
      activities of HEX, HEX A and GALp and insignificant decrease activity of HEX B
      along with the reduction of the CD4+ number. In both HIV positive groups the
      activities of HEX B were statistically lower and GALp statistically higher in
      comparison to the control. In the case of HEX A significant differences could be
      observed between patients with low immunological status and the control group.
      CONCLUSIONS: HIV infection intensifies catabolism glycoconiugates in saliva and
      changes activities of HEX, its isoenzymes A and B and beta-galactosidase. It may
      change susceptibility the cells lining oral cavity to viral and bacterial
      infections.

PMID- 17458099
TI  - Incidence rate of Candida species in the oral cavity of middle-aged and elderly
      subjects.
AB  - PURPOSE: The aim of this study was to determine the incidence rate of oral
      Candida species in middle-aged and elderly subjects. MATERIAL AND METHODS: The
      study carried out in 103 adults aged 35-92 years, in which 32 (31.1%) used
      complet or partial acrylic dentures. Mycological tests were performed by using
      culture (Sabouraud agar) and API 20C AUX (bioMerieux) for identification of the
      species level. Material for analysis included swabs taken from the palate mucosa
      and mucosal part of denture surfaces in denture wearers, as well as, from tooth
      surface and/or dentine carious lesions. The dental caries status of each patients
      was evaluated using DMF index (WHO 1986 criteria). RESULTS: Yeasts of Candida
      genus were isolated in 65/103 (63.1%) adults. The incidence rate of Candida spp.
      was higher in adults without dentures (46/71; 64.8%) compared to denture wearers
      (19/32; 59.4%); however, the differences were not statistically significant (p =
      0.59 > p = 0.05). Candida albicans were the most frequently isolated species, and
      with a comparable rate (p = 0.06), both in adults with and without dentures
      (17/32; 53.1% and 38/71; 53.5%, respectively). In 3 individuals without dentures,
      two other species were found apart from C. albicans, namely C. glabrata (2x) and
      C. krusei (1x). In a total of 11/49 (22.5%) strains belonging to 5 non-C.
      albicans species were detected in adults without dentures, while in denture
      wearers only 2/19 (10.5%) other species were found (C. krusei and C. oralis) (p =
      0.26 > p = 0.05). Strains of C. glabrata species were isolated only from the
      elderly. No significant differences were noted in the incidence of Candida spp.
      between middle-aged subjects (35-44 years) (35/52; 67.3%) and the elderly (> 55
      years) (30/51; 58.8%) (p > 0.05), both in denture wearers and non-denture wearing
      subjects. However, the frequency of oral Candida spp. strains was increased in
      advanced age subgroup 71-92 years (74.2%) compared with 56-70 years (35.0%) of
      elderly subjects (p < 0.05), only in denture wearers (30.0% vs 5.0%) (p < 0.05).
      The sex and DMF index distribution of both subject groups had no significant
      influence on the numbers of Candida spp. detected. CONCLUSIONS: Yeasts of the
      genus Candida were isolated at a comparable rate (p > 0.05) from the oral cavity
      of adults with and without dentures, as well as in middle-aged (35-44 years) and
      elderly subjects (56-92 years). However, a significant difference was observed
      only between elderly subgroups aged 56-70 (35%) and advanced age subgroup 71-92
      years (74%).

PMID- 17458100
TI  - Physical chemistry for the biological sciences.

PMID- 17458101
TI  - [Public health and family medicine: a lost opportunity?].

PMID- 17458102
TI  - [Hospitalizations by ambulatory care sensitive conditions (ACSC) from the general
      practitioner/family physician's point of view].
AB  - Ambulatory care sensitive conditions (ACSC), for example severe cases of asthma,
      pneumonia and heart failure, force to hospitalizations when not preventing. Those
      necessary hospitalizations signal health problems which need better ambulatory
      care, and that can be avoided when care is appropriate. We analyze
      hospitalizations by ACSC from the general practitioner/family physician' point of
      view, and from his typical adaptation to patients' context. As conclusion we
      recommended its use for group management (for health centres or areas), never for
      individual doctors, and better in dynamic temporal series. Its careful use might
      help because signal areas for improvement and health problems needed of better
      management and better coordination in between health care levels.

PMID- 17458103
TI  - [Pest control in urban environments: basic criteria for a rational control
      program design].
AB  - The objectives of urban pest control are those of improving the welfare of urban
      residents, reducing contagious diseases, keeping healthy environments, creating
      urban infrastructures which will reduce risks, as well as reducing exposure to
      biological, physical and chemical contaminants and their health-related effects
      in the working and community environments. Given the characteristics of the urban
      environments in which these animal species and man almost constantly are sharing
      the same living space, it is absolutely essential that a rational control program
      be adopted to combat these pests which will make it possible to reduce or
      eliminate the incidence thereof. An analysis of the basic criteria for the
      rational design of control programs is provided in order to minimize not only the
      negative consequences stemming from these pests but also the risks entailed in
      the application of the measures for their control.

PMID- 17458104
TI  - [Life socioeconomic circumstances, physical inactivity and obesity influences on
      metabolic syndrome].
AB  - BACKGROUND: Majority of the studies have evaluated the independent effect of each
      risk factor on several component of metabolic syndrome. This study investigates
      the influence of accumulation of risk factor through life course (socioeconomic
      circumstances, physical activity and obesity) on the risk of metabolic syndrome
      and their components in older population in Spain. METHOD: We have studied 4009
      subjects representative of the Spanish non-institutionalised population aged 60
      years and older. We have elaborated a measure of exposure through life course
      exposure after combining five risk indicators: low childhood social class, low
      education, low adult social class, physical inactivity and general obesity. The
      indicator has six categories of risk from the most favourable (0 risk factors) to
      the least favourable exposure (5 risk factors). Study participants were
      considered to have metabolic syndrome if they simultaneously had abdominal
      obesity, raised blood pressure and diabetes mellitus. RESULTS: The prevalence of
      abdominal obesity fluctuated between 74.2% and 95.8% in men and between 87.8% and
      99.1% en women, prevalence of raised blood pressure did between 77.5% and 85.0%
      in men and 75.7% and 88.0% in women, and prevalence of diabetes mellitus did
      between 13.0% and 34.8% in men and 7.6% y 25.4% in women. Except for raised blood
      pressure and diabetes mellitus in men, increase was gradual with the number of
      risk factors. The absolute difference in the prevalence of metabolic syndrome
      between people that had the risk indicator profile least favourable and people
      that had the risk indicator profile most favourable through life course was 22%
      in men and 17% in women. CONCLUSIONS: The risk of metabolic syndrome is
      influenced in a cumulative fashion by socioeconomic exposures and risk
      behavioural to health acting throughout the life course. The prevalences of
      abdominal obesity, of raised blood pressure, and of diabetes mellitus show an
      ascending gradient from the most favourable categories of risk to the least
      favourable categories of risk, except for raised blood pressure and diabetes
      mellitus in men

PMID- 17458105
TI  - [Outbreak of viral parotiditis in a school in Bizkaia, Spain, in 2006].
AB  - BACKGROUND: Outbreaks of parotiditis have recently been recorded in Spain and in
      other developed countries. The possible reasons currently under consideration are
      the low degree of immunization coverage among the populations involved and/or the
      low degree of effectiveness of the vaccine strains employed. This study describes
      one outbreak of parotiditis having occurred in Bizkaia and assesses, the
      effectiveness of the vaccine strains and the usefulness of the diagnostic tests
      currently used. METHODS: Those cases having compatible clinical symptoms and an
      epidemiological link within the period under study (February-May 2006) were
      labeled as cases. Blood samples were taken to study IgM and IgG and saliva for
      genotype and RNA detection. The immunization status and the strain used were
      found through the vaccine distribution records. A univariate analysis was
      conducted on the data and relative risks calculated according to the vaccine
      strains used. RESULTS: A total of 63 cases were detected, 52 being students from
      one school. Fifty percent were 9-13 years of age. A total of 88.5% of the cases
      detected at the school had been properly immunized. The IgM sensitivity was 9%,
      PCR sensitivity being 37%. The relative risk of those students immunized with an
      initial dose of Rubini strain as compared to those immunized with Jeryl-Lynn
      strain was 3.8 (95% CI:2.27-6.49). CONCLUSIONS: The high degree of immunization
      coverage does not prevent outbreaks from occurring in places having a high degree
      of exposure. The IgM reveals itself to be sensitive to a very small degree for
      the diagnosis of parotiditis. It seems necessary that the current immunization
      strategies and diagnostic methods be reconsidered.

PMID- 17458106
TI  - [Expectations and needs detected among professionals at provincial organizations
      working in intersectorial action in health].
AB  - BACKGROUND: Intersectorial Action in Health has been the methodology proposed for
      reducing inequality in health. The objectives of this study are to ascertain what
      experiences, expectations and needs are perceived to exist among the
      professionals working at provincial organizations in order to propose a framework
      for analyzing and carrying out intersectorial work. METHODS: With a qualitative
      design, 21 semi-structured individual surveys were conducted in July 2005 of
      professionals from provincial justice, education, health, equality and welfare
      organization and from law enforcement officials in Granada and Seville. An
      intentional -snowball> sampling was used, in which it was possible to complete
      the profile table by way of two individuals answering the survey. RESULTS: The
      professionals identified needs which it would be necessary to cover with the
      intersectorial work as well as the grounds for the same. They highlighted a
      number of personal traits and some organization-related ones and identified
      factors which have been divided among, political, social and operative factors.
      CONCLUSIONS: A consensus exists as to pointing out intersectorial action as a way
      of guaranteeing the reduction of social inequality, given that it prevents
      doubling resources and unifies the response being provided. It was thought to be
      fundamental for some profound changes to first be made in the provincial
      organizations culture in or for the intersectorial work to comprise part thereof.
      These changes must go along with clear-cut guidelines at the upper levels of
      social movements which will clearly highlight the need for a certain
      intersectorial action in particular.

PMID- 17458107
TI  - [Comparability ratios of the total and by sex between ICD-9 and ICD-10 for the
      mortality lists of Murcia and the National Institute of Statistics of Spain].

PMID- 17458108
TI  - [Does age have any bearing on the incidence of extrapulmonary tuberculosis?].

PMID- 17458109
TI  - [Eradicating tuberculosis as a public health problem. A good alternative].

PMID- 17458111
TI  - [Structures and functions of ion channels--for accumulation of basic knowledge
      helpful in medical studies].

PMID- 17458110
TI  - [Changes in the pharmacological pattern of antihypertensive drug use during the
      period 1992-2004 in the autonomous community of the Basque Country, Spain].

PMID- 17458112
TI  - [Metabolic syndrome and adiponectin].

PMID- 17458113
TI  - [Septic shock and NO].

PMID- 17458115
TI  - [Use of digital data in academic activities--on copy rights and good manners].

PMID- 17458114
TI  - [Control of activation of a cell adhesion molecule, integrin].

PMID- 17458116
TI  - [Teaching the real value of anesthesiology: the attraction of anesthesiology that
      you learn through experience and studies and transmit through feelings].

PMID- 17458117
TI  - [Management of a difficult airway during anesthesia--based on the difficult
      airway algorithm proposed by ASA].

PMID- 17458118
TI  - [Studies on neuraxial block using MRI].

PMID- 17458119
TI  - [Perioperative care of schizophrenic patients].

PMID- 17458120
TI  - [Cerebral mechanism related to pain].

PMID- 17458121
TI  - [The effect of general anesthesia on the central nervous system--evaluation on an
      individual level using a mouse model].

PMID- 17458122
TI  - [Euthanasia and death with dignity: logical analysis of the problems].

PMID- 17458123
TI  - [Legal and ethical aspects of death with dignity and euthanasia].

PMID- 17458124
TI  - [Easing pain in palliative care and death with dignity-euthanasia].

PMID- 17458125
TI  - [Future prospect of anesthesiologists who are to become critical care
      physicians].

PMID- 17458126
TI  - [The role of the anesthesiologist in intensive care].

PMID- 17458127
TI  - [A proposal by an anesthesiologist who moved from an operating room to the scene
      of emergency care--co-existence of anesthesiologists and emergency physicians].

PMID- 17458128
TI  - [Anesthesia: "an anesthesiologist can be patients' true ally anywhere in the
      hospital"].

PMID- 17458129
TI  - [Overall image of the anesthetic service area and a cross section of pain clinic
      activities].

PMID- 17458130
TI  - [The mechanism by which an anesthetized state is produced in the body].

PMID- 17458131
TI  - [Elucidation of anesthetic and analgesic effects of ketamine using NMDA receptor
      epsilon 1 subunit-deficient mice].

PMID- 17458132
TI  - [Effect of a general anesthetic on hippocampal synaptic transmission].

PMID- 17458133
TI  - [Description of anesthesia through the xenon binding response in a protein model
      under a pressure-of 2,000-anesthetic binding with low specificity produces
      resistance to pressure with the volume increase].

PMID- 17458134
TI  - [Physiology of edema].

PMID- 17458135
TI  - Report on childhood obesity in China (4) prevalence and trends of overweight and
      obesity in Chinese urban school-age children and adolescents, 1985-2000.
AB  - OBJECTIVE: To describe the nationwide prevalence of childhood overweight/obesity,
      and their group variations and trends over the past 20 years in the Chinese urban
      population. METHODS: Data sets of boys and girls at the age of 7-18 years
      collected from the series of Chinese national surveillance on students'
      constitution and health (CNSSCH) between 1985 and 2000 were divided into five
      socioeconomic and demographic groups, while BMI classification reference proposed
      by Working Group on Obesity in China (WGOC) was used as screening reference to
      calculate the prevalence and trends of overweight/obesity in these groups.
      RESULTS: In 2000, the prevalence of obesity and overweight in boys aged 7-18
      years was 11.3% and 6.5% in Beijing, 13.2% and 4.9% in Shanghai, 9.9% and 4.5% in
      coastal big cities, and 5.8% and 2.0% in coastal medium/small-sized cities,
      respectively, while the prevalence of of obesity and overweight in girls of the
      same age group was 8.2% and 3.7% in Beijing, 7.3% and 2.6% in Shanghai, 5.9% and
      2.8% in coastal big cities, and 4.8% and 1.7% in coastal medium/small-sized
      cities, respectively. The prevalence of obesity was low in most of the inland
      cities at an early stage of epidemic overweight. The epidemic manifested a
      gradient distribution in groups, which was closely related to socioeconomic
      status (SES) of the study population. However, a dramatic and steady increasing
      trend was witnessed among all sex-age subgroups in the five urban groups, and
      such a trend was stronger in boys than in girls, and much stronger in children
      than in adolescents. CONCLUSION: Although China is at an early stage of epidemic
      obesity by and large, the prevalence of obesity in her urban population,
      particularly in coastal big cities has reached the average level of developed
      countries. The increasing trend has been rapid since early 1990s, and the
      increments in obesity and overweight are exceptionally high. The prospect of
      epidemic obesity in China is in no way optimistic. Therefore, preventive program
      should be focused on the improvement of the balance between caloric intake and
      energy expenditure, and interventions aimed at changing children's life styles.

PMID- 17458136
TI  - Report on childhood obesity in China (5) body weight, body dissatisfaction, and
      depression symptoms of Chinese children aged 9-10 years.
AB  - OBJECTIVE: To investigate the relationship between body weight, body
      dissatisfaction and depression symptoms among Chinese children. METHODS: The
      fasting body weight and height of the third and fourth grade students (n = 3886,
      aged 9 or 10 years) from 20 schools in Beijing, China, were measured, and the
      students were asked to choose the figures of body image and to complete the self
      reported children's depression inventory (CDI) questionnaire. RESULTS: The CDI
      Cronbach's alpha was 0.81. The total CDI score was 9.60 +/- 7.50, 13.2% of
      children (boys 16.7% vs girls 9.5%) were at risk of developing depression
      symptoms. Overweight girls, but not boys, had significantly higher total CDI
      score than their normal weight counteparts. Both obese girls and boys showed a
      higher negative self-esteem score. More than one fifth underweight girls still
      wanted to be thinner while more than one third obese boys still wanted to be
      heavier. Children who wanted to be thinner showed slightly higher scores of
      ineffectiveness and negative self-esteem. After introducing the body
      dissatisfaction into the model, overweight was still associated with total CDI
      score among girls and obesity was still associated with negative self-esteem
      among both boys and girls. CONCLUSION: Overweight girls show a significantly
      higher depression symptom score than their normal weight counterparts, which
      maybe partially explained by body dissatisfaction. Obese boys and girls are both
      more likely to suffer from low self-esteem, which is partially explained by body
      dissatisfaction.

PMID- 17458137
TI  - Report on childhood obesity in China (6) evaluation of a classroom-based physical
      activity promotion program.
AB  - OBJECTIVES: To evaluate the effect of Happy 10 program on the promotion of
      physical activity, physical growth and development of primary-school students,
      and on obesity control and prevention. METHODS: Two similar primary schools from
      one district of Beijing, China were selected, one as an intervention school and
      the other as a control school. Happy 10 program was implemented at least once
      every school day in the intervention school for two semesters, whereas no
      intervention was adopted in the control school. The information on energy
      expenditure and duration of physical activity was collected by a validated 7-day
      physical activity questionnaire. Height and weight were measured by trained
      investigators following the standardized procedure. Energy expenditure and
      intensity of each Happy 10 session was measured by a physical activity monitor.
      RESULTS: The average energy expenditure and duration of total physical activity
      per day among students in the intervention school increased significantly from
      15.0 to 18.2 kcal/kg, and 2.8 to 3.3 h respectively, whereas the figures
      significantly decreased in the control school. There was a significant difference
      in change of weight and BMI between girls in the intervention and control school
      (2.4 kg vs 4.6 kg, -0.47 kg/m2 vs 0.66 kg/m2). The prevalence of overweight and
      obesity in the intervention school decreased by 0.4%-5.6%, as compared to the
      increase by 0.6%-4.5% in the control school. The average energy expenditure and
      intensity per 10-minute session ranged from 25.0-35.1 kcal, 4.8-6.2 kcal/kg/h
      respectively in grades 1-5. CONCLUSION: Happy 10 program provides a useful
      strategy to promote physical activity among school children and also plays a
      positive role in building up physical growth and development of girls.

PMID- 17458138
TI  - Protein profile of human lung squamous carcinoma cell line NCI-H226.
AB  - OBJECTIVE: To construct a database of human lung squamous carcinoma cell line NCI
      H226 and to facilitate discovery of novel subtypes markers of lung cancer.
      METHOD: Proteomic technique was used to analyze human lung squamous carcinoma
      cell line NCI-H226. The proteins of the NCI-H226 cells were separated by two
      dimensional gel electrophoresis and identified by mass spectrometry. RESULTS: The
      results showed that a good reproducibility of the 2-D gel pattern was attained.
      The position deviation of matched spots among three 2-D gels was 1.95 +/- 0.53 mm
      in the isoelectric focusing direction, and 1.73 +/- 0.45 mm in the sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis direction. One hundred and twenty
      seven proteins, including enzymes, signal transduction proteins, structure
      proteins, transport proteins, etc. were characterized, of which, 29 identified
      proteins in NCI-H226 cells were reported for the first time to be involved in
      lung cancer carcinogenesis. CONCLUSION: The information obtained from this study
      could provide some valuable clues for further study on the carcinogenetic
      mechanism of different types of lung cancer, and may help us to discover some
      potential subtype-specific biomarkers of lung cancer.

PMID- 17458139
TI  - Serum amyloid A protein: a potential biomarker correlated with clinical stage of
      lung cancer.
AB  - OBJECTIVE: To identify serum diagnosis or progression biomarkers in patients with
      lung cancer using protein chip profiling analysis. METHOD: Profiling analysis was
      performed on 450 sera collected from 213 patients with lung cancer, 19 with
      pneumonia, 16 with pulmonary tuberculosis, 65 with laryngeal carcinoma, 55 with
      laryngopharyngeal carcinoma patients, and 82 normal individuals. A new strategy
      was developed to identify the biomarkers on chip by trypsin pre-digestion.
      RESULTS: Profiling analysis demonstrated that an 11.6 kDa protein was
      significantly elevated in lung cancer patients, compared with the control groups
      (P < 0.001). The level and percentage of 11.6 kDa protein progressively increased
      with the clinical stages I-IV and were also higher in patients with squamous cell
      carcinoma than in other subtypes. This biomarker could be decreased after
      operation or chemotherapy. On the other hand, 11.6 kDa protein was also increased
      in 50% benign diseases of lung and 13% of other cancer controls. After trypsin
      pre-digestion, a set of new peptide biomarkers was noticed to appear only in the
      samples containing a 11.6 kDa peak. Further identification showed that 2177 Da
      was a fragment of serum amyloid A (SAA, MW 11.6 kDa). Two of the new peaks, 1550
      Da and 1611 Da, were defined from the same protein by database searching. This
      result was further confirmed by partial purification of 11.6 kDa protein and MS
      analysis. CONCLUSION: SAA is a useful biomarker to monitor the progression of
      lung cancer and can directly identify some biomarkers on chip.

PMID- 17458140
TI  - Association of a common haplotype of hepatocyte nuclear factor 1alpha with type 2
      diabetes in Chinese population.
AB  - OBJECTIVE: To analyze the association of variants of hepatocyte nuclear factor
      1alpha (HNF-1alpha) gene with type 2 diabetes in Chinese population. METHODS: In
      152 unrelated type 2 diabetes patients and 93 unrelated controls, eleven single
      nucleotide polymorphisms (SNPs) were identified and genotyped. Statistical
      analyses were performed to investigate whether these SNPs were associated with
      diabetes status in our samples. RESULTS: In the individual SNP study, no SNP
      differed significantly in frequency between type 2 diabetes patients and
      controls. In the haplotype analysis, two haplotype blocks were identified. In
      haplotype block 1, no evidence was found between common HNF-1alpha haplotypes and
      type 2 diabetes. However, in haplotype block 2, a common haplotype GCGC formed by
      four tagging SNPs (tSNPs) was found to be associated with decreased risk of type
      2 diabetes (odds ratio [OR] 0.6011, 95% confidence interval [CI] 0.4138-0.8732, P
      = 0.0073, empirical P = 0.0511, permutation test). A similar trend was also
      observed in the diplotype analysis, indicating that the increasing copy number of
      the haplotype GCGC was associated with the decreased frequency of diabetes (P =
      0.0193). CONCLUSION: The results of this study provide evidence that the
      haplotype of HNF-1alpha decreases the risk of type 2 diabetes in Chinese
      individuals.

PMID- 17458141
TI  - Action of Schwann cells implanted in cerebral hemorrhage lesion.
AB  - OBJECTIVE: To investigate whether there is neogenesis of myelin sheath and neuron
      after transplantation of Schwann cells into cerebral hemorrhage lesion. METHODS:
      Schwann cells were expanded, labeled with BrdU in vitro and transplanted into rat
      cerebral hemorrhage with blood extracted from femoral artery and then injected
      into the basal nuclei. Double immunohistochemistry staining and electron
      microscopy were used to detect the expression of BrdU/MBP and BrdU/GAP-43 and
      remyelination. RESULTS: BrdU/MBP double positive cells could be seen at 1 week up
      to 16 weeks after transplantation of Schwann cells. Thin remyelination was
      observed under electron microscope. GAP-43 positive cells appeared after 12 weeks
      and were found more in Hippocamp. CONCLUSIONS: Grafted Schwann cells participate
      in remyelination and promoter nerve restore in rat cerebral hemorrhage.

PMID- 17458142
TI  - Is KPNB3 locus associated with schizophrenia?
AB  - OBJECTIVE: To reconfirm the association of KPNB3 with schizophrenia in Chinese
      population. METHODS: Two single nucleotide polymorphisms (SNPs), rs2588014 and
      rs626716 at the KPNB3 locus, were genotyped in 304 Chinese Han family trios
      consisting of fathers, mothers, and affected offsprings with schizophrenia. These
      2 SNPs were detected by PCR-based restriction fragment length polymorphism (RFLP)
      analysis. The Hardy-Weinberg equilibrium for genotypic distributions was
      estimated by the goodness-of-fit test. The UNPHASED program was used to perform
      transmission disequilibrium test (TDT), haplotype analysis, and pair-wise measure
      of linkage disequilibrium (LD) between these 2 SNPs. RESULTS: The genotypic
      distributions of both rs2588014 and rs626716 were in the Hardy-Weinberg
      equilibrium (P > 0.05). The TDT revealed allelic association with rs626716 (chi2
      = 9.31, P = 0.0023) but not with rs2588014 (chi2 = 3.44, P = 0.064). The global P
      value was 0.0099 for 100 permutations. The haplotype analysis also showed a
      disease association (chi2 = 25.97, df = 3, P = 0.0000097). CONCLUSION: The
      present study provides further evidence in support of the KPNB3 association with
      schizophrenia in Chinese population.

PMID- 17458143
TI  - Effect of pre-treatment of alpha-ketoglutarate on cyanide-induced toxicity and
      alterations in various physiological variables in rodents.
AB  - OBJECTIVE: To investigate the effects of pre-treatment of alpha-ketoglutarate
      (alpha-KG) on cyanide-induced lethality and changes in various physiological
      parameters in rodents. METHODS: The LD50 of potassium cyanide (KCN) given orally
      (po), intraperitoneally (ip), subcutaneously (sc) or intravenously (iv) was
      determined in male mice, in the presence or absence alpha-KG given po, ip or iv.
      alpha-KG was administered 10, 20 or 40 min prior to KCN at 0.50, 1.0 or 2.0 g/kg
      by po or ip route, and at 0.10, 0.20 or 0.40 g/kg by iv route. Protection index
      (PI) was calculated as the ratio of LD50 of KCN in the presence of alpha-KG
      (protected animals) and LD50 of KCN in the absence of alpha-KG (unprotected
      animals). In a separate experiment, several physiological variables viz. mean
      arterial pressure (MAP), heart rate (HR), respiratory rate (RR), neuromuscular
      transmission (NMT) and rectal temperature (RT) were measured in anesthetized
      female rats pre-treated (-10 min) with po (2.0 g/kg) or iv (0.125 g/kg) alpha-KG
      and then administered sub-lethal (0.75 LD50) or lethal (2.0, 4.0 or 8.0 LD50)
      doses of KCN (po). RESULTS: PI of 4.52, 6.40 and 7.60 at -10 min, 3.20, 5.40 and
      6.40 at -20 min, and 1.40, 3.20 and 5.40 at -40 min of po administration with a
      KG was observed for 0.50, 1.0 and 2.0 g/kg doses, respectively, against KCN given
      by po route. When KCN was given ip, a PI of 3.38, 4.79 and 5.70 was observed for
      0.50, 1.0 and 2.0 g/kg alpha-KG given ip (-10 min), respectively. A lower PI of
      3.37, 2.83 and 2.38 was observed when KCN given sc was challenged by 2.0 g/kg
      alpha-KG given ip at -10, -20 or -40 min, respectively. Similarly, a PI of 3.37,
      2.83 and 2.0 was noted when KCN given sc was antagonized by 2.0 g/kg alpha-KG
      given po at -10, -20 or -40 min, respectively. No appreciable protection was
      observed when lower doses of alpha-KG (ip or po) challenged KCN given by sc
      route. Pre-treatment of iv or po administration of alpha-KG did not afford any
      protection against KCN given po or iv route. Oral treatment of 0.75 LD50 KCN
      caused significant decrease in MAP and HR after 15 min, RR after 30 min and NMT
      after 60 min. There was no effect on RT. No reduction in MAP, HR, RR and RT was
      observed when rats received 2.0 or 4.0 LD50 KCN after pre-treatment of alpha-KG
      (po; 2.0 g/kg). However, no protection was observed on NMT. Protective efficacy
      of alpha-KG was not observed on MAP, HR, RR, and NMT decreased by 8.0 LD50 KCN.
      Decrease in MAP and NMT caused by 2.0 LD50 KCN (po) was resolved by iv
      administration of alpha-KG. CONCLUSIONS: Cyanide antagonism by alpha-KG is best
      exhibited when both alpha-KG and KCN are given by po route. The protective effect
      of a-KG on cyanide-induced changes in several physiological parameters also
      indicates a promising role of alpha-KG as an alternative cyanide antidote.

PMID- 17458144
TI  - Specific detection of toxigenic vibrio cholerae based on in situ PCR in
      combination with flow cytometry.
AB  - OBJECTIVE: To develop an in situ PCR in combination with flow cytometry (ISPCR
      FCM) for monitoring cholera toxin positive Vibrio cholerae. METHODS: In running
      this method, 4% paraformaldehyde was used to fix the Vibrio cholerae cells and 1
      mg/mL lysozyme for 20 min to permeabilize the cells. Before the PCR thermal
      cycling, 2.5% glycerol was added into the PCR reaction mixture in order to
      protect the integrality of the cells. RESULTS: A length of 1037bp DNA sequence
      was amplified, which is specific for the cholera toxin gene (ctxAB gene). Cells
      subjected to ISPCR showed the presences of ctxAB gene both in epifluorescence
      microscopy and in flow cytometric analysis. The specificity and sensitivity of
      the method were investigated. The sensitivity was relatively low (10(5)
      cells/mL), while the specificity was high. CONCLUSION: We have successfully
      developed a new technique for detection of toxigenic Vibrio cholerae strains.
      Further study is needed to enhance its sensitivities. ISPCR-FCM shows a great
      promise in monitoring specific bacteria and their physiological states in
      environmental samples.

PMID- 17458145
TI  - Effects of wastewater discharge on heavy metals pollution in Fadama soils in Kano
      City, Nigeria.
AB  - OBJECTIVE: To present the results of a research project on 6 heavy metals (Cd,
      Cu, Zn, Pb, Hg, and Cr) at 30 Fadama fields scattered around Kano. METHODS:
      Following a reconnaissance conducted, 30 representative Fadama lands being
      irrigated with wastewater were selected from zones of the city under residential,
      industrial, commercial, and mixed but largely residential landuses. Five
      additional Fadama lands not being irrigated with wastewater were selected to
      serve as control. Using grid sampling procedure, soil samples were selected from
      0-15 cm and 20-30 cm depths and analyzed for the above listed heavy metals using
      atomic absorption spectrophotometry. T-test was used to compare the mean values
      of the metals for the Fadama lands under different landuse zones with those of
      the control. RESULTS: Analyses of the soil data collected showed that the metals
      were concentrated in higher amounts in the lower (20-30 cm) than the upper (0-15
      cm) depths, which was an indication of downward movement of the metals in profile
      of the soils. In the two soil depths, Zn was generally the most abundant,
      followed by Cr, then Pb, Cu, and Cd while Hg was the least. The Fadama soils in
      areas of mixed landuses with industrial as the dominant ones maintained the
      highest concentrations of the various metals. CONCLUSIONS: These results indicate
      clearly that the Fadama soils are significantly polluted by industrial and
      household wastewater and that there is a particular threat from Cr and Pb
      pollution. There is also evidence that the metals are accumulating at lower
      layers of the soil profile, suggesting that not only plants and soil, but even
      water bodies could be under the threat of heavy metal pollution in the area.

PMID- 17458146
TI  - A novel biosensor for the rapid determination of biochemical oxygen demand.
AB  - OBJECTIVE: To investigate the function of a novel biosensor used for the rapid
      determination of biochemical oxygen demand (BOD) which is developed by our
      research group based on suspended immobilized microbial cell system in a
      completely mixed determining chamber as a substitute of the traditional membrane
      system. METHODS: Activated sludge was immobilized by PVA gel and used as a bio
      sensing element. The novel biosensor was used to measure the short time BOD value
      and the conventional cultivation method was used for BOD5 measurement. RESULTS: A
      linear relationship was observed for the difference between the current and the
      concentration of glucose-glutamic acid (GGA) solution below 200 mg/L with a
      correlation coefficient of 0.995. The optimal response of the sensor was obtained
      at pH 7.0 and 30 degrees C. The sensor response was within 15 min and was
      reproducible within +/- 5% of the mean in a series of eight samples containing 75
      mg/L BOD using standard GGA solution. The novel sensor response was found to be
      fairly constant over a period of 30 days, with +/- 5% fluctuations. CONCLUSION: A
      relatively good agreement is found between BOD estimated by the novel BOD
      biosensor and that determined by the conventional 5-day BOD method. This novel
      BOD biosensor has good sensitivity, stability and reproducibility.

PMID- 17458147
TI  - Consumption of mercury-contaminated rice induces oxidative stress and free
      radical aggravation in rats.
AB  - OBJECTIVE: To study the oxidative stress induced by consumption of mercury
      contaminated rice in rats, and to assess the possible public health risk of
      mercury contamination in Wanshan mining area. METHODS: Sprague Dawley rats were
      fed the mercury-contaminated rice produced from Wanshan area for 90 days. The
      antioxidant status and the free radicals in rat serum were evaluated. RESULTS:
      High mercury accumulation in organs of rats fed the mercury-contaminated rice
      confirmed the server pollution of mercury in Wanshan mining area. The intensity
      of electron spin resonance (ESR) signal increased by 87.38% in rats fed the rice
      from Wanshan compared with that in the control rats fed the rice from Shanghai,
      suggesting that chronic dietary consumption of rice from mercury mining area
      could induce an aggravation of free radicals. Feeding the mercury-contaminated
      rice was associated with significant decreases in the antioxidant enzymatic
      activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and
      concentration of serum nitric oxide (NO), but it had no effect on serum nitric
      oxide synthase (NOS) activity. Feeding the mercury-contaminated rice raised the
      level of serum malonyldialdehyde (MDA), indicating the occurrence of oxidative
      stress. CONCLUSION: The long-term dietary consumption of mercury-contaminated
      rice induces the aggravation of free radicals and exerts oxidative stress.

PMID- 17458148
TI  - [Redefining treatment of rheumatic arthritis with anti-cytokines].

PMID- 17458149
TI  - [Recent advances in the pathophysiology of hyperuricemia and gout].
AB  - Gout is due to the formation and tissue deposition of MSU crystals. Hyperuricemia
      promotes crystal formation and results from the disequilibrium between the
      synthetic and elimination rates of uric acid. Recent studies have elucidated the
      mechanisms of renal handling of uric acid by specific transporters (URATI and
      OAT) which play a role in uric acid excretion. MSU crystals provoke inflammation
      by activating leukocytes to produce inflammatory cytokines. One mechanism is
      through the TLR2 and TLR4 receptors, which form part of the innate immune system.
      MSU crystals can also activate a protein complex called the inflammasome, which
      in turn activates IL-1 processing to yield the secreted mature form of IL- 1beta.
      The inflammatory effects of MSU can be blocked by IL-1 inhibitors. These advances
      could provide new targetted therapeutic approaches to treat hyperuricemia and
      gout.

PMID- 17458150
TI  - [Clinical manifestations of gout].
AB  - Gout is a chronic disease, clearly progressing in incidence and prevalence, which
      threaten to pose a real problem of public health in the near future. Gout is to
      be understood for as the progression in a continuum of a single and same disease:
      hyperuricemia. This awareness allows to better apprehend the disease's evolution,
      to understand clinical manifestations and to plan treatment in a rational way.

PMID- 17458151
TI  - [Advances in the management of gout].
AB  - Gout is the most frequent cause of man's inflammatory arthritis after forty years
      of age and its prevalence is increasing. Although the physiopathology of this
      condition is starting to be thoroughly recognized, therapeutic approaches have
      not fundamentally changed during the last decades. In the absence of renal or
      digestive contraindications, non steroidal inflammatory drugs are the treatment
      of choice for acute flares of gout arthritis. If an indication for urate-lowering
      therapy exists, a xanthine oxydase inhibitor or an uricosurical treatment remains
      the treatment of choice, depending on the patient's co-morbidity. Purine
      restrictive diet, weight loss in case of obesity and lower alcohol intake are
      highly necessary co-measures.

PMID- 17458152
TI  - [Calcium pyrophosphate dihydrate crystal induced arthropathy].
AB  - CPPD deposition disease is a common and potentially severe arthropathy.
      Hyperparathyroidism, hemochromatosis and hypomagnesaemia can favour
      chondrocalcinosis and must be looked for in early disease (< or =60 years).
      Chondrocalcinosis can cause severe attacks of inflammatory arthritis (pseudogout)
      as well as various forms of chronic arthropathies including pseudo RA, pseudo OA
      and pseudo neuropathic joint disease. Diagnosis is based on synovial fluid
      analysis, (positively birefringent CPPD crystals) and X-rays (punctuated and
      linear radio densities in cartilage). NSAIDs and i.a. or systemic glucocorticoids
      are the most useful treatments. Colchicine can be effective in recurring
      pseudogout, and magnesium for attacks' prevention. Methotrexate proved effective
      in a small uncontrolled series, and can be used when other treatments fail.

PMID- 17458153
TI  - [Apatite deposition diseases].
AB  - Deposition of apatite crystals can be observed as calcific periarthritis and
      articular calcifications. Deposition of these crystals in the tendons and bursae
      of the rotator cuff of the shoulder is found in about 3% of adults; it is most of
      the time asymptomatic. Calcifications often totally disappear after an acute
      flare up. Intraarticular apatite crystals can be identified in synovial fluids of
      patients with severe destructive osteoarthrosis, mainly of the shoulder joints.
      Management with NSAID's and local corticosteroid injections is often very
      helpful. In rare cases the aspiration with a needle of a calcification or an
      operative removal is necessary.

PMID- 17458155
TI  - [The fatigue of Mrs. B].

PMID- 17458154
TI  - [Osteoporosis and hypercalcemia of indeterminate origin].

PMID- 17458156
TI  - [The brutality of James Bond and the global influence of violence in the media].

PMID- 17458157
TI  - [Some ethical precautions before entering the nanoworld].

PMID- 17458158
TI  - [Non heart beating organ donation: history and ethics].

PMID- 17458159
TI  - [Camembert cheese, Normandy and Escherichia coli].

PMID- 17458160
TI  - [Protection against Buruli ulcer by aquatic insect saliva?].

PMID- 17458161
TI  - [Screening of lung cancer by CT: a time of uncertainty].

PMID- 17458162
TI  - [Pharmacist prescribing].

PMID- 17458163
TI  - Design of active small interfering RNAs.
AB  - Small interfering RNAs (siRNAs) have become the experimental tool of choice to
      suppress gene expression in a wide variety of organisms. Site selection and
      optimization does not appear to be as difficult for siRNAs as would be expected
      from historical experience with antisense oligonucleotides. Nevertheless, not all
      sites within a target gene perform equally. Significant progress has been made in
      defining sequence features that contribute to siRNA potency, and a variety of
      computational tools are available from academic and commercial sources to assist
      with siRNA design. Potential siRNA sequences should be screened for homology to
      other genes within the target organism's transcriptome to minimize cross
      hybridization and inadvertent knockdown of unrelated genes via off-target
      effects. In addition to rational design criteria, chemical modification of the
      RNA can improve function by improving stability, reducing the potential for off
      target effects and avoiding stimulation of the innate immune system.

PMID- 17458164
TI  - Intranasal antisense therapy: preclinical models with a clinical future?
AB  - Recent progress in the development of two antisense strategies--DNA
      oligonucleotides and RNA interference for the treatment of respiratory diseases
      are discussed in this review. Appropriate formulations and chemical modifications
      for improved stability should foster the clinical application of antisense drugs,
      but the delivery of antisense drugs to their intended target tissue remains the
      biggest challenge for most therapeutic applications of these compounds. The nose
      provides a particularly attractive route for antisense drug delivery to the
      respiratory system; however, significant hurdles remain.

PMID- 17458165
TI  - The development and future of oligonucleotide-based therapies for cervical
      cancer.
AB  - Cervical cancer is an attractive model in which to test gene-specific therapies,
      because elimination of the HPV oncogenes E6 and E7 may result in cancer cell
      senescence. Oligonucleotide-based therapies tested over the years include
      antisense oligonucleotides, ribozymes and, more recently, small interfering RNA
      (siRNA)-based treatments. The development and use of these technologies are
      reviewed. siRNA-based therapies have been touted as potential treatments for
      cancers, genetic disorders and viral infections and have a number of advantages
      over antisense and ribozyme technologies. As with the older technologies, in
      vitro testing of siRNAs against cervical cancer has shown promising results,
      however, the issues that held up the clinical development of ribozymes and
      antisense are currently also challenging the siRNA field; these are target
      selection, specificity and delivery. If these issues can be overcome, a range of
      new and potent therapies for cervical cancer could become available.

PMID- 17458166
TI  - DNAzymes as potential therapeutic molecules.
AB  - Numerous DNA-based biopharmaceuticals are able to control disease progression by
      induction and/or inhibition of genes. These potent therapeutics include plasmids
      containing transgenes, antisense oligonucleotides, aptamers, ribozymes, DNAzymes
      and short interfering RNAs. DNAzymes, which cleave RNA substrates in a sequence
      specific manner, have been studied as potential therapeutics to target pathogenic
      mRNAs, and may yield drugs that are safer than those currently available. This
      reviewo discusses the structural design of DNAzymes and their modification for
      stability. Their therapeutic application and use as biomarkers is also discussed.

PMID- 17458167
TI  - Using aptamers to identify and enter cells.
AB  - While nucleic acid binding species (aptamers) have previously been selected
      against a variety of biomedically important protein targets, the selection of
      aptamers against complex targets, such as cell surfaces and organisms, is
      becoming increasingly feasible. A number of aptamers have now been generated that
      can target specific cell-surface antigens and cell types, including tumor
      biomarkers and tumor cells. The generation of anti-cell aptamers has important
      implications for identifying disease-specific biomarkers, generating diagnostics,
      and developing novel drug delivery strategies.

PMID- 17458168
TI  - Engineered transcription factors for therapeutic angiogenesis.
AB  - Angiogenesis is defined as the growth and proliferation of blood vessels from
      existing vascular structures. Therapeutic angiogenesis seeks to harness the
      mechanisms of vascular growth to treat disorders of inadequate tissue perfusion.
      Early clinical trials of therapeutic angiogenesis met with limited success, in
      part due to the complex spatial and temporal regulation of angiogenesis, which
      requires the coordinate action of multiple growth factors and their receptors.
      Engineered transcription factors represent a novel and innovative approach to
      modulate this process as they offer the ability to induce expression of multiple
      angiogenic genes simultaneously. The rational design of these transcription
      factor agents, results of their use in preclinical models of ischemic disease and
      prospects for their use in human investigations are discussed in this review.

PMID- 17458169
TI  - New therapeutic targets for antibodies and recombinant proteins in organ
      transplantation.
AB  - The development of immunosuppressive drugs for tolerance induction or maintenance
      of an allograft is the key to successful organ transplantation. Humanized mAbs
      are promising biological agents because of their reduced immunogenicity and
      favorable bioactivity. Although their clinical application has so far been
      limited to the anti-CD3 and anti-recombinant IL-2 mAbs, new antibodies have been
      developed against several targets, including cell-surface molecules involved in T
      cell activation, proliferation and trafficking. In addition, developments within
      the field of bioengineering have allowed for the production of fusion molecules
      with enhanced bioactivity. One such molecule, belatacept, which inhibits the T
      cell costimulatory pathway, has been shown to improve long-tern transplant
      outcome as part of a calcineurin inhibitor-free maintenance imnmunosuppressive
      regimen. The specialized immunosuppressive agents currently in clinical use, in
      preclinical development, and in early clinical trials for transplantation are
      discussed in this review.

PMID- 17458170
TI  - Specific immunotherapy in pollen allergy.
AB  - Pollen allergy affects at least 10% of the global population, and up to one-third
      of the affected individuals displaying hay fever symptoms will later develop
      allergic asthma. The efficacy of allergen-specific immunotherapy (SIT) in
      seasonal allergic rhinitis has been confirmed in many clinical studies using
      grass, ragweed, and birch pollen extracts. SIT prevents the onset of new
      sensitizations to different allergens, and reduces the development of asthma in
      patients with allergic rhinitis caused by inhaled allergens, including pollen.
      Several rational approaches are being developed to improve the efficacy of SIT by
      reducing immunoglobulin (Ig)E-mediated adverse reactions. The use of chemically
      modified, recombinant or genetically engineered allergens is being explored, in
      addition to the investigation of novel adjuvants and alternative routes of
      administration. The first clinical trials using recombinant allergens provided
      encouraging results, suggesting that allergen extracts can be successfully
      substituted by molecule-based formulations. These new formulations, for use in
      the routine management of pollen allergies, should become available in the near
      future.

PMID- 17458171
TI  - Immune-based prevention of mother-to-child HIV-1 transmission.
AB  - Vertical transmission, or mother-to-child transmission (MTCT), is the main mode
      of HIV-1 acquisition in infants and children. The presence of passively
      transferred maternal antibodies to HIV-1 has not protected infants front HIV-1
      infection and there is no clear understanding about the role of antibodies in
      preventing MTCT. Immune factors, such as leukemia inhibitory factor, CC
      chemokines, Lewis X component and secretory leukocyte protease inhibitor, appear
      to be involved in the protection of HIV-exposed, uninfected infants. The mainstay
      of reducing HIV transmission risk in infants remains the use of antiretroviral
      therapy. Future strategies to augment the role of antiretrovirals in preventing
      MTCT, or to target the prevention of transmission through breastfeeding, may
      include the use of vaccination and/or passive immunization with neutralizing
      monoclonal antibodies.

PMID- 17458172
TI  - Active and passive immunization for atherosclerosis.
AB  - This review summarizes experimental findings that highlight the role of immune
      mechanisms in atherosclerosis and the potential atheroprotective effects of
      active or passive immunization strategies. Inmmunomodulation therapy appears to
      be feasible and effective, suggesting that a vaccine for atherosclerosis can be
      developed for clinical testing. Given the increasing number of patients with
      atherosclerotic disease on current therapy, a new therapy is needed and an
      immunization strategy could provide such a possibility. Several questions
      regarding this approach remain unanswered, however, such as choice of optimal
      antigens, choice of most effective adjuvants, the optimal route of
      administration, durability of effects and safety, but cautious optimism remains
      that a vaccine-based approach has the potential to become a part of the
      armamentarium for atherosclerotic vascular disease.

PMID- 17458173
TI  - Drug evaluation: Therion's rV-PSA-TRICOM + rF-PSA-TRICOM prime-boost prostate
      cancer vaccine.
AB  - Therion Biologics Corp is developing PROSTVAC-VF-TRICOM, a prime-boost vaccine
      regimen that consists of a priming injection with a recombinant attenuated
      vaccinia virus expressing PSA and TRICOM (the company's proprietary triad of
      costimulatory molecules: ICAM-1, B7.1 and lymphocyte function-associated antigen
      3), and a booster injection with a fowlpox virus expressing the same combination,
      for the potential treatment of prostate cancer. Phase II clinical trials are
      underway.

PMID- 17458174
TI  - Drug evaluation: adecatumumab, an engineered human anti-EpCAM antibody.
AB  - Micromet Inc, in collaboration with Merck Serono SA, is developing adecatumumab
      for the potential treatment of adenocarcinomas, including breast and prostate
      cancer. Adecatunmumab is a fully human antibody targeting epithelial cell
      adhesion molecule (EpCAM). Adecatumumab is currently undergoing phase II clinical
      trials in breast and prostate cancer.

PMID- 17458175
TI  - Drug evaluation: zanolimumab, a human monoclonal antibody targeted against CD4.
AB  - Merck Serono SA, under license from Genmab A/S and Medarex Inc, is developing
      zanolimumab, a human mAb targeted against CD4, for the potential treatment of
      cutaneous (CTCL) and noncutaneous (NCTCL) T-cell lymphomas. Zanolimumab is
      currently undergoing phase III clinical trials for CTCL and phase II clinical
      trials for NCTCL.

PMID- 17458176
TI  - Major developments in the endocrine and metabolic field between 2006 and 2007.

PMID- 17458177
TI  - Sodium-glucose cotransporter inhibitors for diabetes.
AB  - In the search for potential new drug targets for the treatment of diabetes,
      sodium-glucose cotransporters (SGLTs), in particular SGLT2, have been the subject
      of particular attention. SGLT2 plays an important role in glucose reabsorption in
      the kidney, and SGLT2 inhibitors enhance renal glucose excretion and consequently
      lower plasma glucose levels. Thus, SGLT2 inhibitors can control energy balance in
      a negative direction. The principle behind SGLT2 inhibition involves the
      improvement of diabetic conditions without increasing body weight or the risk of
      hypoglycemia. A number of pharmaceutical companies are evaluating SGLT2
      inhibitors, and studies have confirmed the therapeutic potency and safety of
      these drugs for the potential treatment of diabetes.

PMID- 17458178
TI  - A new paradigm in the treatment of osteoporosis: Wnt pathway proteins and their
      antagonists.
AB  - The need to develop novel drugs that stimulate bone formation and thereby elevate
      bone mass (anabolics), as opposed to preventing bone loss (anti-resorptives), has
      opened new research areas for therapeutic intervention in the treatment of
      osteoporosis. One of these areas is the Wnt/beta-catenin (canonical) pathway that
      plays an important role in regulating osteoblast proliferation and
      differentiation. Alterations in this pathway have been associated with bone
      disorders characterized by either low or high bone mass. However, as the Wnt/beta
      catenin pathway is a ubiquitous mechanism not just exclusively involved in bone
      formation, targeting Wnts may be a challenge (eg, targeting Wnt activity may
      induce cancer). Nevertheless, specific pharmacological targets to influence bone
      formation have been identified in this pathway; these include the Wnt-lipoprotein
      receptor-related protein 5/6-frizzled complex and Wnt antagonists such as
      sclerostin. Since sclerostin expression is highly restricted to osteocytes, this
      specific target may be ideal for anabolic drug therapy.

PMID- 17458179
TI  - Targeting the RANK/RANKL/OPG signaling pathway: a novel approach in the
      management of osteoporosis.
AB  - The discovery of the unique role of the receptor activator of nuclear factor
      kappaB (RANK)/RANK ligand (RANKL)/osteoprotegerin signaling pathway in the
      process of osteoclastogenesis has led to the targeting of this pathway as a novel
      therapeutic approach in the management of osteoporosis. In a phase II clinical
      trial, a single subcutaneous administration of denosumab, a high-affinity, high
      specificity, fully human monoclonal antibody to RANKL, led to a profound and
      prolonged inhibition of bone resorption, which was associated with significant
      increases in bone mineral density in postmenopausal women. The anti-fracture
      efficacy, and skeletal and extraskeletal safety issues of denosumab are being
      addressed in ongoing phase III clinical trials. The potential of RANKL as a
      therapeutic target in the treatment of osteoporosis is discussed in this review.

PMID- 17458180
TI  - The sea within us: disorders of body water homeostasis.
AB  - The use of a sensitive radioimmunoassay to measure plasma vasopressin led to the
      clarification of the role of vasopressin in most clinical hyponatremic states, an
      advance that had been impossible with the less sensitive bioassay for
      antidiuretic hormone. The cloning of the V2 vasopressin receptor on the
      basolateral membrane of the principal cells of the collecting duct demonstrated
      that the majority of congenital nephrogenic diabetes insipidus (NDI) was caused
      by mutations in this V2 receptor gene. The Nobel Prize discovery of the first
      membrane water channel by Agre and colleagues allowed for the molecular
      understanding of many disorders of water homeostasis, several of which are
      discussed in this review. Mutations of the vasopressin-regulated water channel on
      the principal cells of the collecting duct, namely aquaporin (AQP)2, account for
      a minority of cases of congenital NDI. Downregulation of AQP2 expression has
      subsequently proved important in an array of clinically significant causes of
      acquired NDI. Most important clinically, has been the discovery of several orally
      active, non-peptide V2 receptor antagonists, which have significant implications
      in the treatment of hyponatremic states. This review discusses the major advances
      that have increased our understanding of the mechanisms of renal water regulation
      in health and disease. The relationship between osmotic and non-osmotic
      regulation of antidiuretic hormone (arginine vasopressin) release is discussed.

PMID- 17458181
TI  - Modulation of carnitine palmitoyltransferase-1 for the treatment of obesity.
AB  - The rising incidence of obesity, as a disorder of energy metabolism, has provoked
      a search for pharmacological agents that either increase energy expenditure or
      reduce food intake. The fatty acid oxidation pathway, and its rate-limiting
      enzyme carnitine palmitoyltransferase (CPT)-1 are potential targets for the
      treatment of obesity. The modulation of CPT-1 may simultaneously affect energy
      metabolism and food intake to aid in the management of obesity. Both the
      inhibition and enhancement of CPT-1 activity are currently under investigation as
      strategies for the treatment of obesity. In this review, key data on both sides
      of the 'CPT-1 activity balance' as they relate to obesity therapy are discussed.

PMID- 17458182
TI  - Update on the development of male hormonal contraceptives.
AB  - Efficacy trials have shown that male hormonal contraceptives can be effective,
      safe and reversible. A combination of a long-acting injectable testosterone plus
      a progestin is most likely to be the first commercially available male hormonal
      contraceptive. Some potential daily oral or transdermal testosterone plus
      progestin formulations are also being investigated. In addition, researchers have
      discovered promising novel drugs such as selective androgen receptor modulators
      and oral gonadotropin-releasing hormone antagonists that may prove useful in male
      hormonal contraceptive regimens. This review briefly summarizes some of the more
      recent findings in the development of male hormonal contraceptives.

PMID- 17458183
TI  - Drug evaluation: K-111, an insulin-sensitizing peroxisome proliferator-activated
      receptor alpha agonist.
AB  - Kozva Co Ltd, under license from Roche Holding AG, is developing K-111, an orally
      available peroxisome proliferator-activated receptor a ligand and insulin
      potentiating agent, for the potential treatment of type 2 diabetes. Phase II
      clinical trials of K-111 are underway.

PMID- 17458184
TI  - Drug evaluation: PSN-9301, a short-acting inhibitor of dipeptidyl peptidase IV.
AB  - (OSI) Prosidion is developing PSN-9301, a rationally designed dipeptidyl
      peptidase IV inhibitor acquired from Probiodrug AG, as a potential oral treatment
      for type 2 diabetes. Phase II clinical trials of PSN-9301 are underway.

PMID- 17458185
TI  - Drug evaluation: rivoglitazone, a new oral therapy for the treatment of type 2
      diabetes.
AB  - Daiichi Sankyo Inc is developing rivoglitazone, an insulin sensitizer with
      peroxisome proliferator-activated receptor gamma agonistic activity, for the
      potential treatment of type 2 diabetes. By March 2006, phase I/III clinical
      trials were underway in the US and the EU.

PMID- 17458186
TI  - [Significance and future problem of metabolic syndrome as a modern illness].

PMID- 17458187
TI  - [Definition and history of metabolic syndrome].

PMID- 17458188
TI  - [How to spread the concept of metabolic syndrome].

PMID- 17458189
TI  - [Metabolic syndrome: convergence of metabolic diseases based on obesity and
      dysfunction of adipose tissue].

PMID- 17458190
TI  - [Molecular basis of metabolic syndrome: insulin resistance].

PMID- 17458191
TI  - [Atherosclerotic vascular disease and its prevention in metabolic syndrome].

PMID- 17458192
TI  - [Prevalence of metabolic syndrome and its association with cardiovascular
      diseases].

PMID- 17458193
TI  - [The metabolic syndrome and the national health promotion plans].

PMID- 17458194
TI  - [Leading role of Framingham Heart Study in the epidemiology on cardiovascular
      diseases].

PMID- 17458195
TI  - [Risk of cardiovascular diseases in relation to insulin resistance: the Tanno
      Sobetsu study].

PMID- 17458196
TI  - [The association of metabolic syndrome with coronary heart disease in a general
      Japanese population: the Hisayama Study].

PMID- 17458197
TI  - [Metabolic syndrome and the risk of cardiovascular disease: the Suita cohort
      study].

PMID- 17458198
TI  - [Metabolic syndrome in Japanese patient with diabetes analysis from JDCS].

PMID- 17458199
TI  - [Prevalence of metabolic syndrome in Japan by MONKS (metabolic syndrome and
      abdominal obesity at NTT West Kyoto Study)].

PMID- 17458200
TI  - [Hypothalamic nuclei sense metabolic signals and regulate feeding].

PMID- 17458201
TI  - [Roles of energy metabolism transcription factors].

PMID- 17458202
TI  - [Leptin and feeding regulation].

PMID- 17458203
TI  - [Brain-adipose axis and leptin resistance].

PMID- 17458204
TI  - [Appetite and feeding regulation by free fatty acid].

PMID- 17458205
TI  - [Insulin action and its regulatory mechanisms].

PMID- 17458206
TI  - [Roles of insulin receptor and insulin receptor substrates on insulin
      resistance].

PMID- 17458207
TI  - [The roles of adipokines in the regulation of insulin sensitivity].

PMID- 17458208
TI  - [Muscular insulin resistance].

PMID- 17458209
TI  - [Hepatic insulin resistance and energy homeostasis].

PMID- 17458210
TI  - [Adipocyte dysfunction and insulin resistance].

PMID- 17458211
TI  - [Insulin resistance in central nerve system].

PMID- 17458212
TI  - [Pathogenesis and etiology of cardiovascular disease: role of insulin
      resistance].

PMID- 17458213
TI  - [Insulin resistance in the kidney].

PMID- 17458214
TI  - [The behavior of adipocytes in obesity].

PMID- 17458215
TI  - [The regulatory mechanism (s) of adipocyte differentiation and proliferation].

PMID- 17458216
TI  - [Fat distribution and its regulation].

PMID- 17458217
TI  - [Adiposteroid: pathophysiologic role of intracellular glucocorticoid
      reamplification in adipocytes].

PMID- 17458218
TI  - [Pathophysiologic role of macrophages infiltrated into obese adipose tissue].

PMID- 17458219
TI  - [Insulin resistance in pancreatic beta-cells: possible implication in beta-cell
      glucose toxicity].

PMID- 17458220
TI  - [Adiponectin, visfatin, PAI-1].

PMID- 17458221
TI  - [Leptin].

PMID- 17458222
TI  - [Resistin and TNFalpha].

PMID- 17458223
TI  - [Angiotensinogen].

PMID- 17458224
TI  - [Lipid synthetic transcription factors; SREBP-1 and -2].

PMID- 17458225
TI  - [Role of TFAP2B and Wnt5B in adipose tissue].

PMID- 17458226
TI  - [ChREBP].

PMID- 17458227
TI  - [Kruppel-like transcription factor 5 (KLF5)].

PMID- 17458228
TI  - [PPARalpha, PPARgamma, PPARdelta].

PMID- 17458229
TI  - [AGF/Angpt16].

PMID- 17458230
TI  - [Incretin].

PMID- 17458231
TI  - [Aquaporin adipose (AQPap)].

PMID- 17458232
TI  - [AMPK].

PMID- 17458233
TI  - [Musclin].

PMID- 17458234
TI  - [Cannabinoid system].

PMID- 17458235
TI  - [ACAM, vaspin].

PMID- 17458236
TI  - [EsRAGE].

PMID- 17458237
TI  - [Lipotoxicity and metabolic syndrome].

PMID- 17458238
TI  - [Endothelial dysfunction as a mechanistic factor for metabolic syndrome].

PMID- 17458239
TI  - [Genetic basis of insulin resistance syndrome].

PMID- 17458240
TI  - [Mutations of transcription factors in relation to the metabolic syndrome].

PMID- 17458241
TI  - [Gene mutations of adipocytokine associated with metabolic syndrome].

PMID- 17458242
TI  - [Metabolic syndrome and11beta-hydroxysteroid dehydrogenase type 1 gene
      polymorphisms].

PMID- 17458243
TI  - [A rat model of metabolic syndrome].

PMID- 17458244
TI  - [Transgenic animal models for the study of metabolic syndrome].

PMID- 17458245
TI  - [Clinical features of the metabolic syndrome and its molecular mechanism].

PMID- 17458246
TI  - [Pathogenesis of atherosclerosis in metabolic syndrome].

PMID- 17458247
TI  - [Role of high blood pressure in progression of atherosclerosis in the metabolic
      syndrome].

PMID- 17458248
TI  - [Postprandial hyperglycemia].

PMID- 17458249
TI  - [Hypertriglyceridemia].

PMID- 17458250
TI  - [Hypoalphalipoproteinemia].

PMID- 17458251
TI  - [Metabolic syndrome and small, dense LDL].

PMID- 17458252
TI  - [Clinical significance of remnant lipoprotein in metabolic syndrome].

PMID- 17458253
TI  - [Homocysteine].

PMID- 17458254
TI  - [Smoking].

PMID- 17458255
TI  - [Management of hypertension in metabolic syndrome].

PMID- 17458256
TI  - [Disorder of lipid and lipoprotein metabolism in metabolic syndrome].

PMID- 17458257
TI  - [Pathophysiology and management of impaired glucose tolerance and diabetes with
      metabolic syndrome].

PMID- 17458258
TI  - [Management of obese patient with metabolic syndrome].

PMID- 17458259
TI  - [Pathogenesis and management of hyperuricemia in metabolic syndrome].

PMID- 17458260
TI  - [Thrombosis in the metabolic syndrome].

PMID- 17458261
TI  - [Metabolic syndrome and NAFLD/NASH].

PMID- 17458262
TI  - [Definition and characteristics of the metabolic syndrome in Japan].

PMID- 17458263
TI  - [Global diagnosis definition of the metabolic syndrome and its management].

PMID- 17458264
TI  - [Importance of early diagnosis].

PMID- 17458265
TI  - [Measurement of visceral fat by CT scan].

PMID- 17458266
TI  - [Measurement of intra-abdominal fat by magnetic resonance imaging].

PMID- 17458267
TI  - [Measurement of waist circumference].

PMID- 17458268
TI  - [Abdominal bioelectrical impedance analysis (BIA) method].

PMID- 17458269
TI  - [Abdominal ultrasonography].

PMID- 17458270
TI  - [Assessment for insulin sensitivity (glucose clamp, SSPG, and minimal model)].

PMID- 17458271
TI  - [Insulin tolerance test].

PMID- 17458272
TI  - [Homeostasis model assessment as a clinical index of insulin resistance].

PMID- 17458273
TI  - [Usefulness of pulse wave velocity in monitoring vascular change in metabolic
      syndrome].

PMID- 17458274
TI  - [Measurement of IMT by echotomography].

PMID- 17458275
TI  - [Evaluation of atherosclerosis of coronary artery by intravascular ultrasound and
      coronary angioscopy].

PMID- 17458276
TI  - [Relation of hs-CRP and metabolic syndrome in epidemiological study].

PMID- 17458277
TI  - [High molecular weight form adiponectin].

PMID- 17458278
TI  - [Leptin-to-adiponectin ratio as a new marker associated with metabolic disease].

PMID- 17458279
TI  - [The urinary index of intracellular glucocorticoid reactivation--a novel marker
      of metabolic syndrome and type 2 diabetes].

PMID- 17458280
TI  - [Essential concept of dietary therapy for metabolic syndrome].

PMID- 17458281
TI  - [Screening of functional foods and scientific evidences].

PMID- 17458282
TI  - [Preventive effects of supplemental n-3 polyunsaturated fatty acids on metabolic
      syndromes].

PMID- 17458283
TI  - [Practical method of formula diet for metabolic syndrome].

PMID- 17458284
TI  - [Exercise prescription for people with metabolic syndrome].

PMID- 17458285
TI  - [Evidence that exercise prevents metabolic syndrome].

PMID- 17458286
TI  - [Effects of exercise-training on metabolic syndrome].

PMID- 17458287
TI  - [Importance of smoking cessation intervention for subjects with metabolic
      syndrome].

PMID- 17458288
TI  - [Pharmacological therapeutics for the metabolic syndrome].

PMID- 17458289
TI  - [Effects of ARB in metabolic syndrome].

PMID- 17458290
TI  - [Usefulness of long-acting Ca antagonist in hypertensive patients with metabolic
      syndrome].

PMID- 17458291
TI  - [Alpha inhibitor].

PMID- 17458292
TI  - [Statins].

PMID- 17458293
TI  - [Fibrate and its perspective as a drug for metabolic syndrome].

PMID- 17458294
TI  - [Biguanides].

PMID- 17458295
TI  - [Thiazolidinediones].

PMID- 17458296
TI  - [Alpha glucosidase inhibitor].

PMID- 17458297
TI  - [Sulfonylureas and glinides].

PMID- 17458298
TI  - [Anti-obesity drug].

PMID- 17458299
TI  - [Antioxidant drugs as the strategy for treatment of metabolic syndrome].

PMID- 17458300
TI  - [Therapeutic approach to obesity based on the regulatory mechanism of feeding
      behavior and energy metabolism].

PMID- 17458301
TI  - [Signaling molecules as the therapeutic targets for the metabolic syndrome].

PMID- 17458302
TI  - [Adipocytokines: target for treatment of metabolic syndrome].

PMID- 17458303
TI  - [Intracellular glucocorticoid reactivating enzyme, 11beta-HSD1 as a promising
      drug target against metabolic syndrome].

PMID- 17458304
TI  - [Endoscopic and laparoscopic managements for morbidly obese patients].

PMID- 17458305
TI  - [Gene therapy for metabolic syndrome].

PMID- 17458306
TI  - [Current status of new drug development for metabolic syndrome].

PMID- 17458307
TI  - [Metabolic syndrome and regeneration medicine].

PMID- 17458308
TI  - [Practical benefits of application of clinical path to the patients with
      metabolic syndrome].

PMID- 17458309
TI  - [Recent trends in obesity in children in Japan and its management].

PMID- 17458310
TI  - [New health assessment and life style modification advice program for metabolic
      syndrome in Japan].

PMID- 17458311
TI  - [Efficacy of leptin-replacement therapy in patients with lipoatrophic diabetes].

PMID- 17458312
TI  - [Werner syndrome and metabolic syndrome].

PMID- 17458313
TI  - [Metabolic syndrome associated with polycystic ovary syndrome].

PMID- 17458314
TI  - [Metabolic syndrome in offspring with intrauterine undernutrition].

PMID- 17458315
TI  - [Sleep apnea syndrome and metabolic syndrome].

PMID- 17458316
TI  - [Anorexia of aging].

PMID- 17458317
TI  - Suicide among the young: it is still a crisis!

PMID- 17458318
TI  - The role of the hypothalamic-pituitary-adrenal axis dysfunction in the
      pathophysiology of alcohol misuse and suicidal behavior in adolescents.
AB  - Alterations in the mechanisms that regulate hypothalamic-pituitary-adrenal (HPA)
      axis activity predate the development of alcohol use disorders. Human and animal
      studies indicate that chronic alcohol consumption induces a persistent impairment
      in the ability of the HPA axis to respond to stress. Therefore, HPA axis
      abnormalities may contribute to the development of alcohol use disorders and may
      be a result of alcohol misuse. HPA axis interacts with serotonergic mechanisms.
      Hippocampal function is modulated by serotonergic projections mostly from dorsal
      raphe nucleus in the midbrain. Glucocorticoids modulate the activity of this
      raphe-hippocampal system in various ways. These effects are mediated via central
      corticosteroid receptors, which include glucocorticoid and mineralocorticoid
      receptors located in the hippocampus and in other cortical structures. An
      association between suicidal behavior and hyperactivity of the HPA axis has been
      suggested. An abnormal interaction between the HPA mechanisms and serotonergic
      systems may substantially contribute to suicidal behavior in adolescents, because
      abnormalities in HPA and serotonin functions may be inherited and may manifest at
      young age. Vulnerability to alcohol use disorders and suicide is likely to be due
      to multiple interacting genetic loci of small to modest effects. The
      identification and treatment of adolescents at risk for suicide is one of the
      most critical issues in adolescent psychiatry. The identification of alcohol and
      drug misuse is critical to the proper assessment of suicide risk in adolescents.
      HPA dysregulation may contribute to both alcohol abuse and suicidal behavior in
      adolescents. Studies of HPA function in alcohol abusing adolescents may lead to
      the development of new diagnostic tests for predisposition to suicidal behavior.
      Furthermore, study of biological markers may help us towards an understanding of
      the neurophysiological substrates of severe dysphoric mood states, alcohol and
      substance abuse, and suicidal behavior in adolescents.

PMID- 17458319
TI  - Functional magnetic resonance imaging in studies of the neurobiology of suicidal
      behavior in adolescents with alcohol use disorders.
AB  - Functional MRI of the brain is a technique that localizes regions of activity in
      the brain following task activation. It is useful to neuroscientists interested
      in interrogating the localization of certain brain functions. Alcohol misuse is a
      complex, multidimensional disorder involving problematic ethanol ingestion and
      reflected in behavior. Genetic factors play an important role in the
      etiopathogenesis of alcohol abuse in adolescents. Alcohol use disorders tend to
      run in families with 40-60% of the variance of risk explained by genetic
      influences. Numerous well-designed twin, adoption, and family studies have
      demonstrated that genetic factors are important in determining vulnerability to
      alcohol use disorders. There is a tendency for people who misuse alcohol to marry
      individuals who also abuse alcohol (assortative mating). Thus, many adolescent
      alcohol misusers are from families with a high proportion of alcohol abuse or
      dependence. It has been shown that alcohol abusing adolescents have a number of
      cognitive deficits. Neuropsychological studies of adolescents with alcohol use
      disorders have reported decrements in language skills, problem solving, verbal
      and non-verbal retention, working memory, and visuospatial performance. Some
      cognitive deficits may be present before an adolescent starts drinking and
      contribute to the development of alcohol use disorders. Data suggest that
      neuropsychological dysfunction may play a role in determining risk for suicidal
      acts. Therefore, studies of cognitive impairments and the neural substrate of
      these impairments in alcohol abusing adolescents may help develop methods of
      identifying teenagers who are at increased risk for suicide and contribute to our
      knowledge of the neurobiology of suicidal behavior and may lead to the
      development of new treatment methods.

PMID- 17458320
TI  - Ethnicity and the relationship between adolescent alcohol use and suicidal
      behavior.
AB  - Adolescent suicide is the 3rd leading cause of death in the United States and
      alcohol consumption is estimated to cause adolescent males to be up to 17 times
      more likely to attempt suicide, and females three times more likely to attempt
      suicide. Suicide and suicide attempt rates vary across different ethnicities.
      Also, associated psychopathology, stressors and substance use differ across
      ethnic groups in adolescents. In an exhaustive review of the literature, we found
      that depressed Asian-American youth were four times more likely to display
      suicidal behavior when compared to other Asian youths with other diagnoses; and
      depressed African-American females were more likely to report suicidal ideation
      than male adolescents. We also found that Asian-Americans who experience high
      parental conflict are 30 times more likely to engage in suicidal behavior when
      compared to Asian-American youths with low parental conflict. African-American
      adolescents are 6.4 times more likely to attempt suicide as a result of parental
      conflict. With respect to alcohol use and dependence, Caucasian adolescents were
      twice as likely as the African American victims to have used alcohol before
      committing suicide. Alcohol use among adolescents was associated with increased
      suicidal behavior. Cultural differences in alcohol consumption may account for
      disparities, however future research is needed to further examine cultural trends
      in suicidal behavior and alcoholism.

PMID- 17458322
TI  - Precipitants of adolescent suicide: possible interaction between allergic
      inflammation and alcohol intake.
AB  - Suicide is a leading cause of mortality among adolescents. There is a pressing
      public health need to investigate triggers and novel vulnerabilities for suicide
      in order to improve risk assessment and develop innovative prevention strategies.
      Alcohol is a well established risk factor for adolescent suicide. In this paper,
      we outline a novel mechanism linking allergy, alcohol, and suicide, reviewing (a)
      the association between allergic inflammation, depression, and suicide; and (b)
      the role of alcohol in inducing phosphorylation and rearrangement of tight
      junction proteins of the blood-brain barrier (BBB) resulting in increased
      "leakiness", i.e. passage of cells and molecules. Seasonal peaks of suicide in
      spring have been consistently reported, but their causality is poorly understood.
      A preliminary epidemiologic study found increased nonviolent suicide rates in
      females in spring during intervals of high tree pollen, in comparison to similar
      intervals of low tree pollen. This initial report added to the emerging
      literature proposing a relationship between allergy and depression, and is being
      further pursued at clinical, epidemiological, animal and postmortem tissue
      levels. We propose that allergic inflammation influences depression-related brain
      function via molecular and cellular mediators, but those mediators have a very
      limited access to the brain when the BBB is intact. Alcohol intake disrupts BBB,
      allowing increased brain exposure to cellular mediators of allergy. Considering
      the greater prevalence of allergy in adolescence when alcohol use starts, studies
      investigating the connection between allergy, alcohol, and suicide should be
      expanded to also include a focus on youth.

PMID- 17458323
TI  - Childhood abuse and adolescent suicidality: a direct link and an indirect link
      through alcohol and substance misuse.
AB  - Childhood abuse is responsible for a variety of outcomes that are characterized
      by maladjustment and maladaption. Two of the most significant results are suicide
      and alcohol and substance misuse. This paper explores the direct link between
      childhood abuse and adolescent suicide, the direct link between childhood abuse
      and adolescent alcohol and substance misuse, the indirect link between childhood
      abuse and adolescent suicide through alcohol and substance misuse, and finally
      implications of these links for practitioners working with adolescents who are
      experiencing or who have experienced childhood abuse. Both suicide and alcohol
      and substance misuse are prevalent in the adolescent population; however those
      adolescents who were victims of childhood abuse show an even greater prevalence
      of both suicidality and substance and alcohol misuse. Additionally adolescents
      who exhibit alcohol or substance misuse show greater rater of suicidality than
      those without alcohol and substance misuse. It appears that abuse is a risk
      factor for eventual suicidality. Practitioners working with children or
      adolescents who have experienced abuse need to work towards secondary prevention
      by identifying, predicting and treating those at risk for substance abuse and/or
      suicide; and those working with adolescents who are already abusing substances
      and/or are suicidal should work with the adolescent to identify and examine life
      events such as abuse that may have triggered the chain towards substance misuse
      and/or suicidal ideation.

PMID- 17458321
TI  - Suicidality, depression, and alcohol use among adolescents: a review of empirical
      findings.
AB  - Suicide is a serious health problem as it is currently the third leading cause of
      death for teenagers between the ages of 15 and 24 years. Depression, which is
      also a serious problem for adolescents, is the most significant biological and
      psychological risk factor for teen suicide. Alcohol use remains extremely
      widespread among today's teenagers and is related to both suicidality and
      depression. Suicidality refers to the occurrence of suicidal thoughts or suicidal
      behavior. The consensus in empirical research is that mental disorders and
      substance abuse are the most important risk factors in both attempted and
      completed adolescent suicide. Therefore, it is incumbent upon researchers to
      identify the factors that can lead to their prevention among today's youth. This
      review compiles the existing literature on suicidality, depression, and alcohol
      use among adolescents spanning over the past 15 years. Both Problem Behavior
      Theory and Stress-coping Theory can explain the relationships among suicidality,
      depression and alcohol use. The prevention of suicidality is critical, especially
      during the early school years, when it is associated with depression and alcohol
      use. Suicidality, depression and alcohol use are three phenomenon that noticeably
      increase in adolescence marking this time period as an ideal opportunity for
      prevention efforts to commence. Future empirical work is needed that will further
      assess the impact of adolescent depression and alcohol use on suicidality. In
      sum, this review of empirical research highlights critical results and
      limitations, as well as indicates a need for continued efforts in preventing
      suicidality, depression, and alcohol use among adolescents.

PMID- 17458324
TI  - Preventing suicide in adolescents with alcohol use disorders.
AB  - Adolescent suicide is an escalating crisis that needs to be addressed by
      clinicians and researchers. Alcohol use has consistently been implicated in
      adolescent suicide and it is generally assumed that alcohol use leads to an
      increased risk in suicidality, suicide attempts and completed suicides. It can
      lead to adolescent suicidality through alcohol myopia, disinhibition, and
      impaired judgment. Multiple genetically related intermediate phenotypes might
      contribute to the risk of alcohol misuse and suicidal behavior in adolescents.
      Genetic variations that enhance the risk for mood and anxiety symptoms or
      susceptibility to stress might increase risk through different mechanisms.
      Comorbid disorders such as depression are frequently exhibited in adolescents who
      misuse alcohol, therefore any adolescent who appears to be at risk for alcoholism
      or depression should always be screened for all other psychiatric disorders and
      for suicidality; some signs suicidal adolescents may exhibit include withdrawal,
      personality change, and a loss of interest in pleasurable activities. While
      assessment is important, prevention is crucial in any attempt to decrease the
      incidence of adolescent suicide. The US Center for Disease Control and Prevention
      (CDC) has established a set of seven guidelines that can be implemented from
      kindergarten through high school in order to establish alcohol prevention efforts
      in schools. Through beginning prevention efforts at a young age, it is hopeful
      that both alcohol misuse and adolescent suicide can be reduced.

PMID- 17458325
TI  - The role of the pediatrician in preventing suicide in adolescents with alcohol
      use disorders.
AB  - Worldwide, suicide is among the top five causes of mortality in the 15- to 19-
      year age group. Pediatricians and primary care providers are in a distinctive
      position to help prevent suicide in adolescents. According to the Guidelines for
      Adolescent Preventive Services, all adolescents should have at least an annual
      preventive services visit, which should address both the biomedical and
      psychosocial aspects of health. Suicide prevention may best be accomplished by
      detection and management of specific risk factors, rather than by attempting to
      recognize those youth who are considered most likely to commit suicide. Alcohol
      use has been regarded as an important risk factor for adolescent suicidal
      behavior and the diagnosis of an alcohol use disorder indicates an elevated risk
      for adolescent suicide. Although the causal relationship between alcohol use and
      suicide remains unknown, a clear and strong relationship exists. Pediatricians
      and other health care providers should be skilled to recognize risk factors for
      adolescent suicide, including alcohol and drug misuse, depression, major loss,
      and recent suicides within a community. The relative frequency of suicidal
      behavior among adolescents suffering from alcohol use disorders and its
      distressing effects on individuals, families and society merits further research
      and development of prevention strategies in general pediatric settings.

PMID- 17458326
TI  - Parental alcoholism predicts suicidal behavior in adolescents and young adults
      with cannabis dependence.
AB  - Little is known about the association between cannabis abuse/dependence, comorbid
      alcohol and substance use, depression, suicidal ideation and suicidal behavior.
      OBJECTIVES: To establish the lifetime occurrence of depression, suicidal ideation
      and suicidal behavior in a group of very heavy cannabis users seeking treatment
      and to investigate the significance of a range of social, family and contextual
      factors with special emphasis on alcohol. STUDY GROUP: 119 subjects recruited
      from 19 different substance treatment centers in Denmark. METHODS: Structured
      questionnaires and assessment for psychiatric disorders using Schedules of
      Clinical Assessment in Neuropsychiatry (SCAN), and Beck Depression Inventory (BDI
      II). Lifetime use and dependence of substances was established using parts of
      Addiction Severity Index (ASI), parts of Composite International Diagnostic
      Interview (CIDI) and Alcohol Use Disorders Identification Tests (AUDIT). RESULTS:
      Lifetime depression (46%), suicidal ideation (42%), and suicidal behavior (23%)
      were highly frequent. These problems were more common among females and related
      to adverse childhood experiences and parental alcoholism, while it could not be
      demonstrated that comorbid alcohol or other drug use increased the risk. Parental
      alcoholism remained significantly related to depression (p < .009), suicidal
      ideation (p < .001), and suicidal behavior (p < .03) after adjustment for a range
      of possible confounders using logistic regression. Physical abuse during
      childhood was associated with suicidal ideation (p < .01) and reporting an 'all
      in all bad childhood' was associated with suicidal behavior (p < .03) adjusting
      for the same control variables. CONCLUSIONS: Depression, suicidal ideation and
      suicidal behavior are common phenomena among heavy cannabis users predicted from
      factors related to childhood and parental alcoholism.

PMID- 17458327
TI  - Pathological personality traits and suicidal ideation among older adolescents and
      young adults with alcohol misuse: a pilot case-control study in a primary care
      setting.
AB  - OBJECTIVE: To compare the clinical and demographic characteristics of older
      adolescents and young adults with and without alcohol misuse in a primary care
      setting. METHODS: This study is a case-control study. Eighty-one 18-30 year old
      adolescents and young adults attending a primary care center were assessed with
      the CAGE questionnaire, the PRIME-MD instrument and the IPDE screening
      questionnaire. Sub-samples of positive screen for alcohol misuse (n = 21) and a
      negative age- and gender matched group (n = 21) were compared. RESULTS: Of those
      with alcohol misuse, 71.9% had a comorbid psychiatric diagnosis. Depressive and
      anxiety disorders appeared to be more prevalent among the subjects with alcohol
      misuse than among controls. Among those patients with depressive or anxiety
      disorders and alcohol misuse, 22.2% reported suicidal ideation as compared to
      none among the controls suffering from depressive or anxiety disorders. 69.1% of
      subjects with alcohol misuse had a comorbid personality disorder. Significantly
      more adolescents and young adults with alcohol misuse exhibited borderline
      personality traits (p = 0.03) and there was also a trend towards a greater
      proportion exhibiting histrionic traits (p = 0.07) than among those without
      alcohol misuse. CONCLUSIONS: Adolescents and young adults with alcohol misuse in
      a primary care center have a high prevalence of psychiatric comorbidity. Cluster
      B personality disorders may be more prevalent in the population with alcohol
      misuse. Adolescents and young adults with alcohol misuse may be more likely to
      report suicidal ideation while suffering from depressive or anxiety disorders.
      Further studies that evaluate the clinical and demographic characteristics of
      adolescents and young adults with alcohol misuse attended in a primary care
      center are needed.

PMID- 17458328
TI  - Triggers for suicidal behavior in depressed older adolescents and young adults:
      do alcohol use disorders make a difference?
AB  - Adolescent suicide is a major social and medical problem. Alcohol use disorders
      with comorbid major depression represent an especially high-risk profile for
      suicidal behavior, repeated suicidal behavior and completed suicide. We compared
      demographic and clinical characteristics, prevalence of interpersonal triggers
      and the number of triggers for suicidal behavior in depressed late adolescents
      and young adults with or without comorbid alcohol use disorders. METHODS: 18-26
      year-old subjects were recruited through advertising and referrals and
      participated in mood disorders research in a university hospital. Thirty-eight
      depressed suicide attempters without a history of any alcohol or substance
      abuse/dependence and 29 depressed suicide attempters with comorbid alcohol abuse
      or dependence participated in the study. Demographic and clinical parameters
      including parameters related to suicidal behavior were examined and recorded.
      RESULTS: There was no difference with regard to demographic parameters between
      the two groups. Depressed suicide attempters with comorbid alcohol use disorders
      had higher aggression and impulsivity scale scores and were more likely to be
      tobacco smokers compared to their counterparts without alcohol use disorders.
      Additionally, there was a trend towards higher lethality of suicide attempts in
      subjects with alcohol use disorders compared to the other group. We found no
      difference in the prevalence of interpersonal triggers or in the number of
      triggers for suicidal behavior between the two groups. CONCLUSION: It appears
      that among 18-26-year-old depressed suicide attempters, individuals with comorbid
      alcohol use disorders are more impaired with regard to aggressiveness and
      impulsivity compared to persons without comorbid alcohol abuse/dependence.

PMID- 17458329
TI  - Psychological autopsy studies: the role of alcohol use in adolescent and young
      adult suicides.
AB  - Alcohol abusers seem to be prone to both suicide attempts and completions. The
      relationship between alcohol abuse and suicide in adolescence is complex.
      OBJECTIVES: To examine the role of alcohol abuse and dependence in adolescent
      suicide in psychological autopsy studies. METHOD: A search in the National
      Library of Medicine (NLM) PubMed database using "adolescents" and "all child: 0
      18 years" as the search terms for age and "psychological autopsy" as the search
      term for title or abstract. RESULTS: Forty articles met the selection criteria
      and each one is described. There was a high prevalence of alcohol abuse detected
      in the studies (range 21.42% to 43.47% in samples aged under 20 years). Alcohol
      misuse was present in suicides in the form of chronic abuse, acute abuse and
      dependence. CONCLUSIONS: Alcohol abuse and dependence is highly prevalent among
      adolescent suicides. In many studies, alcohol consumption is analyzed in
      combination with drug abuse. Further studies are necessary to clarify the
      prevalence of chronic and acute alcohol abuse in order to identify specific high
      risk population groups and design antisuicidal interventions for them. Both acute
      and chronic alcohol use should be evaluated when assessing suicide risk in
      adolescents.

PMID- 17458330
TI  - The right number: optimizing panel size.

PMID- 17458331
TI  - Are your payers' fee schedules fair?

PMID- 17458332
TI  - EHRs don't fix everything.

PMID- 17458333
TI  - Electronic health records: the 2007 FPM user-satisfaction survey.

PMID- 17458334
TI  - Strategies for developing a knowledge-driven culture in your practice.

PMID- 17458335
TI  - How to analyze your E/M coding profile.

PMID- 17458336
TI  - Panel size: how many patients can one doctor manage?

PMID- 17458337
TI  - Health care's giant hairball.

PMID- 17458338
TI  - Crooked beak in a 14-month-old ostrich (Struthio camelus) hen.

PMID- 17458339
TI  - Veterinary education in South Africa: the classes of 1928 and 1929.
AB  - The available photographs of the Classes of 1928 and 1929 are confusing because
      they not only bear the same date (1929) but are also composed of individual shots
      of the graduates rather than the customary group photograph. An answer to the
      riddle was provided by the presence of J A Thorburn (a member of the Class of
      1927) who was a 'super' and qualified in 1928, in the one photograph, together
      with M C Robinson who also graduated in 1928. The photograph dated 1929 on which
      4 graduates and the Dean, Prof. Dr P J du Toit, appear is that of the Class of
      1928. The other photograph dated 1929 in which the Dean is absent is therefore
      dated correctly. Concise descriptions are given of the life histories of the nine
      graduates. Their careers show considerable variation. Only one of them spent his
      entire career at the Onderstepoort Research Institute as a very eminent research
      scientist and professor, and two became well-known professors at the
      Onderstepoort Faculty. Two were in municipal service for most of their careers
      and a third ended up working for a municipal authority after spending some time
      in England and at the Onderstepoort Research Institute. Two spent virtually their
      entire careers in the field as state veterinarians and a third farmed for most of
      his career, although he also dabbled in private practice and managed one of the
      provincial game parks in Natal (now KwaZulu-Natal) for some time. Four served in
      the South African Veterinary Corps during World War II.

PMID- 17458340
TI  - The elevated serum urea:creatinine ratio in canine babesiosis in South Africa is
      not of renal origin.
AB  - Pigmented serum, usually due to free haemoglobin and/or bilirubin, is a common
      finding in dogs with babesiosis, resulting in interference with all biochemical
      tests that rely on photochemistry. This is particularly true of urea and
      creatinine determinations, complicating the diagnosis of acute renal failure,
      which is a serious complication of babesiosis. A disproportionately raised serum
      urea concentration of unknown origin occurs in severely anaemic canine babesiosis
      patients and gives rise to an increased serum urea:creatinine ratio. The assay
      for cystatin-C, an excellent measure of glomerular filtration rate, is unaffected
      by free serum haemoglobin, and due to its different intrinsic origins, is free of
      influence by the metabolic derangements and organ pathology, other than renal
      disease, encountered in canine babesiosis. Serum cystatin-C was used to compare
      the concentrations of serum urea and serum creatinine in dogs with the severely
      anaemic form of canine babesiosis as well as a canine babesiosis-free reference
      group. Mean serum urea and mean serum urea:creatinine ratio were significantly
      elevated in the babesia-infected group relative to the reference population in
      this study. Mean serum creatinine and mean serum cystatin-C were within the
      reference ranges. Therefore an elevated urea:creatinine ratio in canine
      babesiosis in the presence of a normal serum creatinine concentration is
      considered to be caused by an elevated serum urea concentration and is most
      likely of non-renal origin. Serum creatinine was therefore as specific a measure
      of renal function as serum cystatin-C in canine babesiosis in this study. The
      sensitivity of serum creatinine as a measure of renal function was not
      established by this study. Serum urea, however, proved to be of little use
      compared to serum cystatin-C and serum creatinine. Serum urea should therefore
      not be used to diagnose renal failure in canine babesiosis.

PMID- 17458341
TI  - Evaluation of the mineral status of cattle on communal grazing in the North West
      Province of South Africa.
AB  - Twenty five cattle were randomly selected from a herd of animals grazing
      communally around Mogosane village in the North West Province to evaluate their
      mineral status based on blood and faecal analysis. Mean faecal phosphorus (P)
      concentration was curvilinear, increasing from July (0.99 mg/g) to December (3.63
      mg/g) and decreasing to 1.29 mg/g in June. Mean P concentration in grass was also
      curvilinear, increasing from July (0.87 mg/g) to January (1.8 mg/g) and
      decreasing to 0.9 mg/g in June. There was a high correlation (r2 = 0.89) between
      faecal and grass P concentrations. Faecal:grass P ratios suggest that the animals
      were conserving P by reducing faecal P excretion during times of low dietary P.
      Animals maintained consistent but very low serum inorganic P (SiP) throughout the
      year (range 1.33-1.95 mg%) and SiP was not correlated with either faecal or grass
      P. Mean faecal and grass calcium (Ca) concentrations followed a similar pattern
      to P. There was also a positive correlation (r2 = 0.95) between grass and faecal
      Ca concentrations. Faecal:grass Ca ratios indicated a conservation of Ca by
      reducing faecal Ca when dietary Ca was low. Animals were better able to conserve
      dietary Ca by reducing losses in the faeces than they were P, based on a higher
      faecal:grass P ratio (1.56) compared with Ca (1.18). Magnesium (Mg) was lost
      through the faeces during times of high dietary Mg concentrations but was
      conserved when grass Mg was low.

PMID- 17458342
TI  - Descriptive study of an outbreak of equine sarcoid in a population of Cape
      mountain zebra (Equus zebra zebra) in the Gariep Nature Reserve.
AB  - An outbreak of equine sarcoid occurred in a population of Cape mountain zebra
      (Equus zebra zebra) at the Gariep Nature Reserve located in the southern Free
      State Province of South Africa in 1996. The course of the outbreak during 1996 to
      2003 is described. During this period the average population size was 69 animals.
      Initially (1996) all affected animals were removed from the population. New cases
      continued to manifest and the incidence varied between 4.6% and 17.6%. Prevalence
      reached 24.7% in 2002. No sexual predilection was noticed in the 39 recorded
      cases. Of the affected individuals, 64% had a single lesion and no animal had
      more than 4 lesions. In males, the majority of lesions occurred in the inguinal
      area (55.17%), whereas in females they mostly occurred on the head and neck
      (41.38%). Lesions can increase 260% in size annually and may impede movement.

PMID- 17458343
TI  - An epidemiological investigation of the African horsesickness outbreak in the
      Western Cape Province of South Africa in 2004 and its relevance to the current
      equine export protocol.
AB  - African Horsesickness (AHS) is a controlled disease in South Africa. The country
      is divided into an infected area and a control area. An outbreak of AHS in the
      control area can result in a ban of exports for at least 2 years. A retrospective
      epidemiological study was carried out on data collected during the 2004 AHS
      outbreak in the surveillance zone of the AHS control area in the Western Cape
      Province. The objective of this study was to describe the 2004 outbreak and
      compare it with the 1999 AHS outbreak in the same area. As part of the
      investigation, a questionnaire survey was conducted in the 30 km radius
      surrounding the index case. Spatial, temporal and population patterns for the
      outbreak are described. The investigation found that the outbreak occurred before
      any significant rainfall and that the main AHS vector (Culicoides imicola) was
      present in abundance during the outbreak. Furthermore, 63% of cases occurred at
      temperatures < or = 15 degrees C, the Eerste River Valley was a high risk area,
      only 17% of owners used vector protection as a control measure and 70% of horses
      in the outbreak area were protected by means of vaccination at the start of the
      outbreak. The study revealed that the current AHS control measures do not
      function optimally because of the high percentage of vaccinated horses in the
      surveillance zone, which results in insufficient sentinel animals and the
      consequent failure of the early warning system. Alternative options for control
      that allow continued export are discussed in the paper.

PMID- 17458344
TI  - Microscopic morphology of Dichapetalum cymosum (Hook.) Engl. as an aid in the
      identification of leaf fragments from the digestive tract of poisoned animals.
AB  - Dichapetalum cymosum (Hook.) Engl. (Poison leaf; gifblaar) is a major cause of
      acute livestock plant poisoning in southern Africa. Microscopic identification of
      leaf fragments found in the digestive tract of poisoned animals can assist in the
      diagnosis of poisoning when D. cymosum poisoning is suspected. The microscopic
      morphology of D. cymosum leaves are described using standard staining and
      microscopy methods for histopathology samples at many regional diagnostic
      laboratories. Morphological descriptions included structures in the epidermis and
      mesophyll that were discernible using H & E staining. The microscopic morphology
      of D. cymosum was used to differentiate between leaf fragments of D. cymosum and
      other species from the same habitat with macroscopic features that resemble those
      of D. cymosum, including Euclea crispa, Combretum zeyheri, Burkea afrikana and
      Lannea discolor.

PMID- 17458345
TI  - Influence of dosage and chemical restraints on feline excretory urography.
AB  - Three series of trials involving 10 domestic short-haired cats were carried out
      to determine the influence of dosage of contrast media or type of chemical
      restraint on feline excretory urography. The 1st series (group A) involved 5 cats
      sedated with 2.0 mg/kg intramuscular (i.m) injection of 2% xylazine and receiving
      800 mg/kg of 76 % meglumine diatrizoate (urografin). The 2nd series (group B)
      involved another 5 cats sedated with 2.0 mg/kg (i.m) injection of 2% xylazine and
      receiving 1200 mg/kg of 76% urografin. The 3rd series (group C) involved the
      repeat urography of the group B cats but sedated with 15 mg/kg (i.m) injection of
      5% ketamine hydrochloride. Ventrodorsal radiographs were obtained immediately, 5,
      15 and 40 minutes after the injection of 76% urografin. Scores were assigned to
      nephrographic opacification as described in the literature. The heart rates,
      respiratory rates and rectal temperatures of the cats were also determined before
      sedation, after sedation, immediately after the injection of 76% urografin and at
      15-minute intervals over a period of 60 minutes. In this study, there were
      significant differences (P < 0.05) in the nephrographic opacification scores
      between the group A and group B cats at times 0 and 40 minutes post
      administration of urografin. Group A cats had good initial nephrographic
      opacification which faded later while the nephrographic opacification of group B
      cats progressively increased. Similarly, nephrographic opacification was
      significantly (P < 0.05) higher in the xylazine-sedated cats (groups A and B)
      than the ketamine-sedated cats (group C). However, there were no significant
      differences (P > 0.05) in heart rates, respiratory rates and rectal temperatures
      between the 3 groups of cats. It was therefore concluded that increasing the
      dosage of urografin above 800 mg/kg in cats does not provide additional
      beneficial effects on the nephrograms produced. Xylazine sedation was observed to
      produce better nephrographic opacification, however, with delayed nephrographic
      fading compared to ketamine sedation.

PMID- 17458346
TI  - Cardiopulmonary effects of medetomidine or midazolam in combination with ketamine
      or tiletamine/zolazepam for the immobilisation of captive cheetahs (Acinonyx
      jubatus).
AB  - Captive cheetah (Acinonyx jubatus) scheduled for either general health
      examination or dental surgery were immobilised with combinations of medetomidine
      ketamine (K/DET, n = 19), midazolam-ketamine (K/MID, n = 4) or medetomidine
      tiletamine-zolazepam (Z/DET, n = 5). Induction time and arterial blood pressure
      was not statistically significantly (P > 0.05) different between treatment
      groups. Transient seizures were observed in the K/DET treated animals during
      induction. Hypertension was present in all groups during anaesthesia with mean
      (+/- SD) systolic pressure of 30.7 +/- 5.0 kPa for the K/DET group, 27.7 +/- 2.7
      kPa for the K/MID group, and 33.1 +/- 4.6 kPa for the Z/DET group. Heart rate was
      statistically significantly (P < 0.05) lower in the K/DET group (69 +/- 13.2
      beats/min) compared to the K/MID group (97 +/- 22.6 beats/min), and ventilation
      rate was statistically significantly (P < 0.05) lower in the K/MID group (15 +/-
      0.0 breaths/min) compared with the K/DET group (21 +/- 4.6). A metabolic acidosis
      and hypoxia were observed during anaesthesia when breathing air. Oxygen (O2)
      administration resulted in a statistically significant (P < 0.05) increase in the
      arterial partial pressure of carbon dioxide (hypercapnoea), arterial partial
      pressure of O2, and % oxyhaemoglobin saturation.

PMID- 17458347
TI  - Congenital dilatation of the large and segmental intrahepatic bile ducts
      (Caroli's disease) in two Golden retriever littermates.
AB  - Two, sibling, male Golden retriever puppies, 13 weeks of age, were presented with
      congenital biliary cysts of the liver involving both hepatic and segmental bile
      ducts, as well as bilateral polycystic kidney disease. Ultrasonography of the
      livers of both pups demonstrated segmental cystic lesions that were contiguous
      with the bile ducts. Histopathology revealed cystic ectatic bile duct hyperplasia
      and dysplasia with variable portal fibrosis in the liver, while in the kidneys
      there were radially arranged, cylindrically dilated cysts of the collecting
      ducts, which extended through the medulla and cortex. This pathology was
      compatible with that of congenital dilatation of the large and segmental bile
      ducts (Caroli's disease) described in humans, dogs and rats. In humans Caroli's
      disease has an autosomal recessive inheritance pattern, while in rats activation
      of the MEK5/ERK cascade initiates the biliary dysgenesis of Caroli's disease in
      this species. However, the exact mode of inheritance and pathogenesis of Caroli's
      disease in dogs is as yet unknown. Previous reports on congenital hepatic cystic
      diseases of the dog have described Caroli's disease like lesions in various
      breeds, but these are believed to be the 1st reported cases in the Golden
      retriever breed.

PMID- 17458348
TI  - Clinical and pathological studies on intoxication in horses from freshly cut
      Jimson weed (Datura stramonium)-contaminated maize intended for ensiling.
AB  - Spontaneous intoxication in 34 horses after ingesting freshly harvested maize
      that was to be used for ensiling and heavily contaminated with young Datura
      stramonium plants, is described. The clinical status of all horses was monitored
      for 7 days, and included body (rectal) temperature, respiratory and heart rates,
      colour and moistness of visible mucosae, changes in pupil size, appetite, thirst,
      general behaviour, locomotion, sensory perceptions, urination and defaecation.
      The intoxication was accompanied by altered clinical status, namely mild
      hyperthermia, tachycardia, polypnoea, dyspnoea and shallow breathing, mydriasis,
      dry oral, rectal, vaginal and nasal mucosae, acute gastric dilatation and severe
      intestinal gas accumulation, anorexia to complete refusal of feed, decreased or
      absent thirst, absence of defaecation and urination. As a result of the
      treatment, the clinical parameters normalised between days 2 and 5. Necropsies
      and pathological studies were performed on two horses that died, revealing toxic
      liver dystrophy, cardiac lesions and substantial dystrophic and necrotic
      processes in the kidneys. The observed clinical signs, the pathomorphological
      changes and the applied therapy could be used in the diagnosis, differential
      diagnosis, prognosis and treatment of Jimson weed intoxication.

PMID- 17458349
TI  - First record of Acanthocheilonema dracunculoides from domestic dogs in Namibia.
AB  - Acanthocheilonema dracunculoides was diagnosed in 2 dogs from Windhoek, Namibia,
      by acid phosphatase staining of microfilariae. This is the 1st record of A.
      dracunculoides in Namibia.

PMID- 17458350
TI  - Mycoplasmal mastitis in dairy cows in the Moghan region of Ardabil State, Iran.
AB  - Mycoplasmas are an important and economically significant cause of mastitis in
      dairy cows in various parts of the world. The organisms are highly contagious,
      with the main reservoir of infection originating from cows with subclinical
      mastitis. In 1998 the 1st cases of bovine mastitis due to Mycoplasma bovis were
      diagnosed in Ardabil State, Iran. An investigation was carried out with the aim
      of establishing the extent of mycoplasma infections in dairy cows in Ardabil
      State. Milk samples obtained from 80 cows with clinical mastitis were cultured in
      the laboratory for the presence of mycoplasmas. Similarly, 48 bulk-tank milk
      samples were examined for the presence of mycoplasmas. A modified Hayflick broth
      was used to isolate the mycoplasmas and an immunoperoxidase test used for the
      species identification of the isolates. Mycoplasma bovis was isolated from 39
      (48.75%) of the clinical mastitis samples and from 48 of the bulk-tank milk
      samples tested. This indicated that mycoplasma udder infections were more
      prevalent in dairy cows in Ardabil State than previously thought.

PMID- 17458351
TI  - Anaesthesia and analgesia for dogs and cats in South Africa undergoing
      sterilisation and with osteoarthritis--an update from 2000.
AB  - A survey was conducted in 2000 into the use of analgesic drugs by veterinarians
      in South Africa. This survey was repeated in 2005 to establish whether the use of
      analgesic drugs has increased and which analgesic drugs are being used for acute
      pain and osteoarthritis. The number of sterilisations performed and the number of
      new cases of osteoarthritis in dogs and cats was estimated. It is estimated that
      approximately 260000 cats are operated on each year in South Africa and that
      150000 cats are sterilised. Five hundred thousand dogs undergo surgery, of which
      242000 are sterilised. It appears that the number of surgical procedures
      performed in South Africa has decreased. The estimated death rate following
      anaesthesia has remained unchanged at 1:1004. Overall, the use of analgesics by
      South African veterinarians has increased significantly. Fifty-six per cent of
      cats and 74% of dogs were given peri-operative analgesics but this increased to
      94% and 84% after including pre-anaesthetic medications with analgesic
      properties. The use of opioids (morphine and buprenorphine) and propofol has
      increased significantly. Approximately 253000 dogs and 33000 cats with
      osteoarthritis are seen by veterinarians in South Africa annually. The
      recognition by veterinarians of osteoarthritis in cats appears to be poor and is
      in need of attention. Carprofen and glucosamine/chondroitin are the most commonly
      used agents for the treatment of osteoarthritis. Details of the drugs used by
      veterinarians are given. Knowledge of analgesic drugs has increased significantly
      over the last 5 years. Continuing education is thought to have played an
      important role in the changes reported in this study.

PMID- 17458352
TI  - [The meaning of 'consensus' in the context of guidelines--an introduction into
      the problem].
AB  - From the point of view of sociology a consensus may be incompatible with science.
      This also applies to consensus statements developed by a scientific medical
      society, since a lack of facts might have been replaced by a majority decision.
      This is in contrast to the idea of evidence-based medicine (EbM). Personal
      beliefs do not gain more plausibility (a higher level of evidence) by the mere
      fact that they are supported by a majority. Thus it is not helpful to demand that
      EbM-oriented guidelines also be consensus-based.

PMID- 17458353
TI  - [Consensus development in evidence-based guidelines: from myths to rational
      strategies].
AB  - Guidelines are meant to be decision aids with precise procedural recommendations
      that are based upon the best knowledge available and thus should contribute to
      improving healthcare delivery. The achievement of this goal necessitates both a
      systematic and methodically sound approach in guideline development. Essential
      elements include the search for and the selection and evaluation of empirical
      evidence for existing knowledge. In addition, personal experience and subjective
      judgements will always be part of guideline recommendations, especially when the
      applicability of the evidence is appraised and health benefits and risks of
      different management options for the disease or condition are considered. To
      achieve high-quality results in this process, formal consensus techniques should
      be employed and potential users and affected patients should be involved. Typical
      of this technique is the structured interaction that provides the framework in
      which contributions of individual participants are documented, made transparent
      and brought together. Quality and acceptance of results are determined by the
      preparation and practical implementation of these procedures, in which individual
      and group-psychological influencing factors play an important role. Along with
      the methods of evidence synthesis, structured consensus building methodology
      represents a cornerstone of guideline development.

PMID- 17458354
TI  - [From evidence to recommendation influence of consensus processes on grades of
      recommendation-'against consensus'?].
AB  - Guidelines are not only sources of condensed evidence. They also contain graded
      recommendations that have been agreed upon in consensus procedures. Frequently
      there are discrepancies between the results of the critical appraisal of the
      evidence expressed in levels of evidence and the strength of the resulting
      recommendations. Unfortunately, the reasons for these discrepancies remain
      largely obscure and guideline users are therefore unable to comprehend this so
      called 'upgrading' or 'downgrading', respectively. A consensus process consisting
      of several stages and a more detailed documentation could be a possible remedy.
      The present contribution is based on a lecture held at the 7th Annual Meeting of
      the DNEbM (German Network for Evidence-based Medicine) in Bochum in March 2006.

PMID- 17458355
TI  - Transferable evidence in support of reaching a consensus.
AB  - The value of consensus recommendations for improving clinical practice may be
      restricted by the limitations of the evidence on which they are based. When few
      high quality studies are identified for evaluation from the specific field of
      interest, selected 'transferable' evidence from comparable clinical situations
      may add important information. Such transferable evidence must be critically
      assessed for relevance to the objective of the recommendations, and must be
      clearly differentiated from specific evidence. In particular, systems for grading
      of recommendations must take into account the different types of evidence used,
      so as not to give equivalent weight to transferable and specific evidence without
      justification. In this article, we discuss the use of transferable evidence by
      the PROSPECT Working Group, which has developed a clinical decision support
      programme (www.postoppain.org) to provide evidence and recommendations for
      procedure-specific postoperative pain management.

PMID- 17458356
TI  - [Participation of patients in the program for national disease management
      guidelines--current state and implications].
AB  - Patient involvement has been implemented in the Program for National Disease
      Management Guidelines since 2005. Currently patient/consumer participation is
      being incorporated in terms of patients' comments of consultation papers on
      National Disease Management Guidelines (NDMG) and in the development of NDMG
      based patient guidelines (PG). The editorial activities in patient guideline
      development from the beginnings to its publication are conducted in close
      cooperation with the patient representatives appointed by the Patient Forum.
      Between June 2005 and September 2006, three NDMG and three patient guidelines on
      asthma, chronic obstructive pulmonary disease (COPD) and chronic coronary artery
      disease (CAD) were produced by including patients in the guideline development
      process. The information provided in these guidelines is freely accessible at
      http://www.versorgungsleitlinien.de. The present contribution focuses on the
      development of patient guidelines. It describes the current state of patient
      involvement and joint work and indicates the implications that can be derived
      from patient participation in the NDMG Program. Accompanying the involvement
      procedures, experiences resulting from previous NDMG and PG development
      activities are continuously investigated for the possibility of further
      methodological development of consumer participation by a work group of the
      Patient Forum in coordination with the patient organizations involved. In
      particular, the procedures resulting from more intensive patient participation in
      patient guideline development are to be examined as to their relevance for the
      expansion of patient involvement in NDMG development.

PMID- 17458357
TI  - [An evidence-based seminar changes cognition rather than medical students'
      personal attitudes towards diagnostic uncertainty in a primary care setting].
AB  - Progress in medical research has led to an increased number of diagnostic tests.
      However, the diagnostic accuracy of these tests often lacks evaluation in the
      primary care setting. Ignorance of evidence-based diagnostic strategies may cause
      a distorted estimation of diagnostic certainty in general practice and may
      increase pointless application of diagnostic tests. This study investigates the
      attitudes of students towards diagnostic accuracy and evaluates whether a seminar
      about evidence-based diagnosis has an impact on these attitudes. 424 medical
      students were asked to complete a questionnaire before and after a 90-minute
      seminar. Before the seminar, 71% of the students thought that due to a lack of
      resources some diagnostic tests--although necessary--are not being reimbursed. At
      the end of the seminar, this proportion was reduced by 12% (p<0.001). The call
      for global reimbursement for all diagnostic tests was reduced by 25% (p<0.001).
      In contrast, there was no change in the proportion of students (21%) that
      incorrectly attributed diagnostic uncertainty to a lower competence of the
      general practitioner. Thus, it seems that after a single seminar there was a
      cognitive change concerning the application of diagnostic tests rather than a
      change in the personal attitudes of students towards diagnostic uncertainty in
      primary care. In this context, the continuous implementation of the principles of
      evidence-based medicine would be necessary to improve the students' decision
      making skills on the basis of a critical attitude including the reasonable
      handling of uncertainties in medical care.

PMID- 17458358
TI  - [The problem of dementia as a price for living a long life].

PMID- 17458359
TI  - [Utilization patterns of dementia patients in the light of statutory health
      insurance data].
AB  - In describing the patterns of utilization of healthcare services by dementia
      patients in comparison to age- and sex-matched controls the study was to provide
      information on special care needs of patients with dementia concerning somatic
      diseases. A representative sample of insured individuals from 1998 to 2002 (the
      "Versichertenstichprobe AOK Hessen/KV Hessen") provided the database. Patients
      with dementia were defined according to the ICD-coded billing diagnoses.
      Regarding general practitioner visits, patients with dementia have approx. 11
      additional contacts per year compared to their controls. A smaller percentage of
      patients with dementia present to a specialist (excluding
      neurologists/psychiatrists). Furthermore, the two groups differ as to the kind of
      specialists visited, which in turn is associated with different service and
      prescription patterns. The study was not able to clarify whether the differences
      are possibly due to the GPs' prioritization of treatment of dementia patients.
      Both physicians and nurses should be sensitized to the possibility that dementia
      patients may not be able to explicitly mention existing diseases and impairments
      (such as cardiovascular and sensory disorders, pain). Moreover, physicians and
      other professionals involved in the management of dementia patients should be
      trained to pay special attention to the particular care-related problems
      (pressure ulcers, infections or inadequate fluid intake).

PMID- 17458360
TI  - [The management of dementia patients from the point of view of office-based
      general practitioners (GPs) and specialists--the results of an empirical
      investigation].
AB  - OBJECTIVE: The objective of the trial was to investigate the differences in the
      management of cognitively impaired and demented patients in Germany between GPs
      and neurologists/psychiatrists in private practice. METHODS: A standardized
      questionnaire was sent out to all 129 GPs affiliated with the German Competence
      Network Dementia (CND; response rate 84%), 260 randomly selected GPs (response
      rate 40%) and 239 randomly selected neurologists/psychiatrists (response rate
      40%) in private practice. RESULTS: Overall, GPs and neurologists/psychiatrists
      showed a positive attitude towards the care of dementia patients. Both GPs and
      specialists emphasized the importance of providing social support to patients and
      caregivers and viewed medical treatment options favorably. Furthermore there was
      broad affirmation of early diagnosis and disclosure of the diagnosis. However,
      several hints suggest the presence of communication difficulties between
      physicians and patients, e.g. 70% of both professional groups provided more
      detailed information to relatives than patients. Differences between GPs and
      neurologists/psychiatrists were found regarding, for example, the use of
      cognitive tests and subjective competence in diagnostic and therapeutic
      procedures, but differences were small. DISCUSSION: Due to the study methods the
      information gained from this survey must be handled with care. Anyway,
      differences between GPs and neurologists/psychiatrists in private practice
      concerning their care for cognitively impaired and demented patients were much
      smaller than expected. The general attitude towards this group of patients was
      positive.

PMID- 17458361
TI  - [IDA project--concept and implementation of a cluster-randomized trial on
      dementia management in a general practice setting].
AB  - Given the multiple deficits in dementia care IDA is a health services research
      project that addresses the key role of general practitioners in the early
      detection of dementia, patient and family education, therapy and referral to
      further counseling and supportive measures. Mid 2005 IDA was started by the AOK
      Bavaria as a pilot project targeting patients living at home. This three-armed
      cluster-randomized trial--currently including 180 participating general
      practitioners--is to compare two supportive measures of different intensity
      (counseling for care-giving relatives and care management) with the usual care in
      terms of time to nursing home placement. Additional outcomes investigated include
      the development of the patient's cognitive status and his abilities to perform
      activities of daily living, burden and quality of life of care-giving relatives
      as well as healthcare costs and costs of institutional care. Participating
      patients with initially mild to moderate disease will be observed for a period of
      two years. Data collection will proceed via general practitioners and caregivers
      and also utilize routine data of statutory health insurances and long-term care
      insurances. Keeping in mind that patient recruitment is ongoing throughout 2006
      the initial analysis of 254 patients' data shows an average 80-year old patient
      in the early phase of moderate dementia. One third of the participants are cases
      with a first- time diagnosis obtained from their general practitioner. Final
      results for IDA are expected to be available in 2009.

PMID- 17458362
TI  - [Multimodal training of general practitioners--evaluation and knowledge increase
      within the framework of the dementia management initiative in general medicine
      (IDA)].
AB  - BACKGROUND AND OBJECTIVE: In many industrialized countries diagnostic and
      therapeutic deficits in the management of patients with dementia are well
      documented. Due to demographic trends the next years will see a further rise in
      the number of affected patients. Accordingly, the knowledge and competence of the
      physicians taking care of these patients need to be keep up-to-date. In the
      context of the three-armed cluster-randomized IDA trial (IDA = "Initiative
      Demenzversorgung in der Allgemeinmedizin"; Dementia Management Initiative in
      General Medicine), general practitioners (GPs) from the trial area (Bavaria,
      Germany) were trained in the diagnosis and treatment of dementia. METHODS: The
      educational training concept was based on the evidence-based guideline of
      Witten/Herdecke University (UWH). All participating GPs (n = 137, January 2006)
      received three hours training in the diagnosis of dementia. In addition, a
      subgroup was trained for two hours in dementia therapy (n = 90). Both groups
      obtained information about the study design. The didactic concept included screen
      and oral presentations by opinion leaders, video and interactive elements. At the
      beginning of the training sessions participants had to fill in a pilot-tested
      questionnaire with 20 multiple choice questions addressing the diagnosis and
      therapy of dementia (pretest). The same questionnaire was completed at the end of
      the training session (posttest) complemented by an evaluation sheet. Overall and
      intergroup differences between pre- and post-test results (increase in knowledge)
      were compared using the Chi-Square test. RESULTS: Overall, the quality of the
      training received a positive rating by the participants. By the end of January
      2006, 137 doctors had been trained. The mean knowledge gain was 4.0+2.6 correctly
      answered questions (p<0.001; Cl 3.6 to 4.5) comparing pre- and posttest (n =
      132). In the group trained on diagnosis alone (n = 45), the gain averaged 2.0+/
      1.9 questions. The group with additional training on therapy (n = 87) achieved a
      difference of 5.1 -2.3 questions (p<0.001). DISCUSSION: Participants of the
      dementia training achieved a substantial gain of knowledge. The extent of this
      knowledge increase was associated with the attendance to respective training
      modules. An ongoing trial will add further information about knowledge
      translation in the field of dementia.

PMID- 17458363
TI  - [Are quality indicators derived from routine data suitable for evaluating
      hospital performance? First results using the AHRQ patient safety indicators in
      Germany].
AB  - Patients and health insurances are increasingly interested in the quality of care
      provided by hospitals. Quality indicators are often used to evaluate the quality
      of inpatient treatment. Most of these evaluations require the collection of
      additional data. The patient safety indicators (PSI) introduced by the Agency for
      Healthcare Research and Quality (AHRQ) are precisely validated and exclusively
      depend on routine data. The original PSI definitions were transferable to the
      classifications of diagnosis, procedures and DRG used in Germany, and applied to
      routine data of 2.3 million cases from more than 200 hospitals. The comparison of
      the results to the US references reveals high concordance between the rates and
      demonstrates that PSI can be applied to detect critical incidents of patient
      care. For PSI-based hospital benchmarking further development of appropriate
      methods of risk adjustment is necessary.

PMID- 17458364
TI  - [Planning, implementation and evaluation of cancer screening programs].
AB  - Members of the Cancer Epidemiology Work Group within the German Epidemiology
      Society and Dr Antes of the German Cochrane Center will present a review of the
      epidemiological aspects of cancer screening programs. Prior to the implementation
      of a cancer screening program, there should be clear evidence from randomized
      controlled trials showing a disease-specific mortality reduction by screening.
      For target entities with the potential to reduce incident invasive cancers- such
      as cervical and colorectal cancer - the search of evidence should also include
      cancer incidence reduction. Monitoring of the screening program is essential and
      should include: the test, the assessment of test-positives, therapy or other
      interventions, and a cause of death evaluation. It is important to show that the
      benefit of a mortality reduction is not outweighed by adverse screening effects.
      In the past, German cancer screening activities were lacking essential components
      of screening programs like a central unit inviting the target population,
      standardized documentation and reporting as well as independent audits. The new
      Mammography Screening Program for the first time offers a screening test in
      Germany that is embedded in a quality monitoring program evaluating at least
      intermediate outcome parameters.

PMID- 17458365
TI  - [Series Epidemiology 5 Multiplicity in randomized studies II: Subgroup analyzes
      and intermediate evaluations].

PMID- 17458366
TI  - Thoughts on being scholarly.

PMID- 17458367
TI  - Defining spirituality and giving meaning to occupation: the perspective of
      community-dwelling older adults with autonomy loss.
AB  - BACKGROUND: In the Canadian Model of Occupational Performance, meaningful
      occupation involves interaction between spirituality and environment. However
      little research exists on the process of giving meaning to occupation. PURPOSE:
      This study explored both meaningful occupation and the definition of spirituality
      from the perspective of community-dwelling older adults with autonomy loss.
      METHOD: Using a qualitative approach, grounded theory method of Glaser and
      Strauss (1967), eight cognitively intact persons were interviewed individually.
      RESULTS: The process of giving meaning to occupation involves an intrinsic link
      between identity and meaningful occupation, with identity being central to the
      person. Following autonomy loss, a process of adjusting identity, involving
      social, psychological and spiritual aspects, occurs over time. Spirituality is
      defined in terms of its close links to religion and belief in a benevolent
      greater power. IMPLICATIONS OF RESEARCH: This study contributes to the discussion
      of the concepts of spirituality, identity and meaning in occupational therapy.

PMID- 17458368
TI  - Discharge decision-making, enabling occupations, and client-centred practice.
AB  - BACKGROUND: Occupational therapists working in hospitals are confronted with
      increasingly complex discharge decisions. However, the relationship of discharge
      planning strategies to the professional concepts of client-centred practice and
      enabling occupations has been unclear. PURPOSE: This study explored the
      relationship between the models of decision-making used by occupational
      therapists, and the professional issues of enabling occupation and client-centred
      practice. METHODS: Qualitative interviews were conducted with 10 occupational
      therapists. Data were analyzed for the presence and emergence of themes. RESULTS:
      Therapists try to balance the sometimes competing issues of safety and autonomy.
      Therapists often engage in negotiated decision-making. However, clients are
      sometimes excluded, despite therapists' commitment to client-centred processes.
      Consideration of occupations is often neglected. PRACTICE IMPLICATIONS: Client
      defined models of decision-making are insufficient for frail, cognitively-
      impaired people. A new, client-centred Negotiated Model of Decision-Making is
      proposed, which facilitates decisions to enable older people with their
      occupations.

PMID- 17458369
TI  - [Clinical utility of three evaluation instruments for persons with dementia].
AB  - BACKGROUND: Occupational therapists are increasingly involved in the diagnostic
      process of cognitive impairment in the elderly. PURPOSE: Three tools designed to
      facilitate the evaluation process were examined in order to document their
      diagnostic qualities and the nature of the association between their results: the
      Mini-Mental State Examination (MMSE), the Protocole d'examen cognitif de la
      personne agee (PECPA-2r) and the Systeme de mesure de l'autonomie fonctionnelle
      (SMAF). METHODS: A cross-sectional correlative study was used in order to
      document the association between the results obtained with the three tools when
      they were used with aging adults referred to the project by their attending
      physician. RESULTS: Fifty-two older adults with a suspected cognitive impairment
      participated in the study. The results of the study indicate that a strong
      correlation exists between the scores obtained with the three evaluation tools.
      The MMSE scores would be an excellent predictor of the PECPA-2r and the SMAF
      scores. The degree of cognitive impairment would be a good predictor of the
      degree of impairment of the autonomy. PRACTICE IMPLICATIONS: Referring physicians
      found some of the evaluators' observations made during the administration of the
      PECPA-2r and the SMAF particularly useful for their subsequent diagnostic
      processes. The shorter administration time for the MMSE did not provide for such
      observations, while the PECPA-2r and the SMAF allowed more time for these kinds
      of observations. Occupational therapists are invited to examine carefully their
      intentions when choosing their evaluation tools.

PMID- 17458370
TI  - A modified constraint-induced movement therapy regimen for individuals with upper
      extremity hemiplegia.
AB  - BACKGROUND: The Constraint-Induced Movement Therapy approach has been identified
      as a promising method to address deficits in upper limb function experienced by
      some stroke survivors. There is some question regarding whether the intervention
      administered in the research setting could be translated into clinical practice.
      PURPOSE: This paper describes the modified version of Constraint-Induced Movement
      Therapy developed at St. Boniface General Hospital, Winnipeg, Canada. METHOD:
      This modified regimen involves practice of upper limb tasks for four hours per
      day for 10 weekdays over two weeks, concurrent with participants attempting to
      wear a restraint mitten on the less involved hand for 90% of their waking hours.
      RESULTS: The primary outcome measure was the Canadian Occupational Performance
      Measure. Two case reports illustrate how the regimen is administered.
      IMPLICATIONS: The need for further research of this regimen in terms of the
      selection of participants, the measurement tools, and the effectiveness is
      discussed.

PMID- 17458371
TI  - Experiences of social class: learning from occupational therapy students.
AB  - BACKGROUND AND PURPOSE: Despite the potential in occupational therapy models,
      there has been little investigation of the ways social class may affect
      occupations or occupational therapy. This paper explores the occupational impacts
      of poverty. METHODS: Essays by 17 occupational therapy students, who identify as
      lower class, were coded and analyzed inductively. RESULTS: Class-based shame and
      stigma led to attempts to "pass" as middle class-an occupation consuming time and
      energy. Exclusion from middle-class leisure occupations left students with gaps
      in their adult knowledge. Family was a site of both shame and safety, as well as
      pressure to succeed. Educational occupations embody marginalization. PRACTICE
      IMPLICATIONS: Class is not only about money, but also having the right norms,
      values, and experiences to fit easily in middle-class society. Educational and
      health care institutions epitomize middle-class assumptions. The experiences of
      these students may help therapists to examine where they unwittingly enact middle
      class norms in practice.

PMID- 17458372
TI  - Exploring the impact of multiple sclerosis on couples: a pilot study.
AB  - BACKGROUND: Multiple sclerosis (MS) is a disease that affects the everyday lives
      of people with MS and their partners. PURPOSE: The purpose of this study was to
      explore the impact of MS on the lives of two couples living with this disease and
      their coping strategies. METHODS: Three semi-structured interviews with each
      couple were completed. Partners were interviewed together as a couple and
      separately. RESULTS: Two major themes emerged from the analysis: increasing
      awareness of change and use of coping strategies. Participants expressed concerns
      stemming from the progression of MS and changes related to this progression over
      time. They discussed several coping strategies. PRACTICE IMPLICATIONS: These
      findings offer occupational therapists guidance with their treatment focus in
      clinical practice and suggest topics for further qualitative research on couples
      living with MS.

PMID- 17458373
TI  - Leaders of the pack. A look at some of the top group practices in the country,
      and how they achieved success.

PMID- 17458374
TI  - Formation of a leader.

PMID- 17458375
TI  - Implementing CPOE--one pill doesn't cure all ills.

PMID- 17458376
TI  - What does it take to retain top physician executives?

PMID- 17458377
TI  - Media CPR: survival tips for physicians.

PMID- 17458378
TI  - Musings on the nature of academic medical leaders.

PMID- 17458379
TI  - How to make innovation happen--part 1.

PMID- 17458380
TI  - A nickel an hour: caring for a health care business.

PMID- 17458381
TI  - Executive coaching--who needs it?

PMID- 17458382
TI  - Second time a winner: managing physician practices with success.

PMID- 17458383
TI  - Hello...time for that telephone interview.

PMID- 17458384
TI  - An ethics agenda for 2007.

PMID- 17458385
TI  - The Supreme Court's Burlington Decision: implications for the health care
      workplace.

PMID- 17458386
TI  - Is it time to stop using budgets to measure performance?

PMID- 17458387
TI  - Should clinicians prescribe forgiveness?

PMID- 17458388
TI  - Adolescents' spirituality and alcohol use.

PMID- 17458389
TI  - Fixed-dose combination therapy in the treatment of hypertension: ready for prime
      time.

PMID- 17458390
TI  - Is this medicine really involved in a drug interaction?

PMID- 17458391
TI  - Abdominal pregnancy--an obstetrical enigma.

PMID- 17458393
TI  - Analysis of HLA antigens in Turkish sarcoidosis patients.
AB  - BACKGROUND: Sarcoidosis is a systemic granulomatous disorder associated with high
      CD4+cell activity, without any detectable pathogen. Clustering in families
      occurs, and the existence of a genetic predisposition to sarcoidosis is widely
      accepted. There are differences among different ethnic groups. METHODS: We
      studied HLA polymorphisms in 64 Turkish patients with biopsy proven sarcoidosis.
      The control group was taken of 160 donor candidates of kidney transplantation
      within the same period. RESULTS: Fifty-one patients were female, and 13 were
      male. The mean age was 39 +/- 6.1 years. Frequency of HLA A2, A9, A24 (9), A25,
      A69 (28), B12, B22, B38, B49 (21), DR4, and DR14 antigens were significantly
      higher, and frequencies of HLA B7 and DR7 were significantly less in sarcoidosis
      patients. Clustering in some families were also noted in our study. CONCLUSIONS:
      This study implies a genetic predisposition to sarcoidosis in the Turkish
      population. Clustering in some families should be kept in mind.

PMID- 17458392
TI  - Alcohol use and religiousness/spirituality among adolescents.
AB  - BACKGROUND: Previous studies indicate that religiousness is associated with lower
      levels of substance use among adolescents, but less is known about the
      relationship between spirituality and substance use. The objective of this study
      was to determine the association between adolescents' use of alcohol and specific
      aspects of religiousness and spirituality. METHODS: Twelve- to 18-year-old
      patients coming for routine medical care at three primary care sites completed a
      modified Brief Multidimensional Measure of Religiousness/Spirituality; the
      Spiritual Connectedness Scale; and a past-90-days alcohol use Timeline Followback
      calendar. We used multiple logistic regression analysis to assess the association
      between each religiousness/spirituality measure and odds of any past-90-days
      alcohol use, controlling for age, gender, race/ethnicity, and clinic site.
      Timeline Followback data were dichotomized to indicate any past-90-days alcohol
      use and religiousness/spirituality scale scores were z-transformed for analysis.
      RESULTS: Participants (n = 305) were 67% female, 74% Hispanic or black, and 45%
      from two-parent families. Mean +/- SD age was 16.0 +/- 1.8 years. Approximately
      1/3 (34%) reported past-90-day alcohol use. After controlling for demographics
      and clinic site, Religiousness/Spirituality scales that were not significantly
      associated with alcohol use included: Commitment (OR = 0.81, 95% CI 0.36, 1.79),
      Organizational Religiousness (OR = 0.83, 95% CI 0.64, 1.07), Private Religious
      Practices (OR = 0.94, 95% CI 0.80, 1.10), and Religious and Spiritual Coping-
      Negative (OR = 1.07, 95% CI 0.91, 1.23). All of these are measures of
      religiousness, except for Religious and Spiritual Coping--Negative. Scales that
      were significantly and negatively associated with alcohol use included:
      Forgiveness (OR = 0.55, 95% CI 0.42-0.73), Religious and Spiritual Coping-
      Positive (OR = 0.67, 95% CI 0.51-0.84), Daily Spiritual Experiences (OR = 0.67,
      95% CI 0.54-0.84), and Belief (OR = 0.76, 95% CI 0.68-0.83), which are all
      measures of spirituality. In a multivariable model that included all significant
      measures, however, only Forgiveness remained as a significant negative correlate
      of alcohol use (OR = 0.56, 95% CI 0.41, 0.74). CONCLUSIONS: Forgiveness is
      associated with a lowered risk of drinking during adolescence.

PMID- 17458394
TI  - Comparison of propofol and sevoflurane for laryngeal mask airway insertion in
      elderly patients.
AB  - BACKGROUND: Sevoflurane and propofol have been widely used for anesthesia
      induction. This study compared the efficacies of sevoflurane and propofol
      inductions for laryngeal mask airway (LMA) insertion in elderly patients.
      METHODS: Ninety patients, aged 60 or more, received anesthesia induction with
      propofol and with sevoflurane 8% using the vital capacity breath (VCB) or tidal
      volume breath (TVB) techniques. Hemodynamic changes, induction time,
      complications, and the quality and ease of LMA insertion were observed. RESULTS:
      LMA was inserted most, less or least rapidly with propofol (89 +/- 28 s),
      sevoflurane 8% using the VCB (163 +/- 34 s) or TVB (205 +/- 44 s) techniques,
      respectively. Anesthesia induction with propofol or sevoflurane 8% using the VCB
      technique produced either more frequent apnea or greater reduction in mean blood
      pressure than with sevoflurane 8% using the TVB technique. CONCLUSIONS:
      Sevoflurane 8% using the TVB technique provides a smoother induction with a
      stable hemodynamic profile, less apnea and technical demand, but requiring longer
      time for LMA insertion in unpremedicated elderly patients.

PMID- 17458395
TI  - Treatment of ankylosing spondylitis with moxifloxacin.
AB  - Ankylosing spondylitis (AS) is a human leukocyte antigen (HLA)-B27-associated
      chronic inflammatory disease of unknown etiology. There are few effective
      treatments for ankylosing spondylitis, which causes substantial morbidity. The
      relationship between AS and enterobacteria, especially Klebsiella pneumoniae, has
      been reported from several groups in several countries. We performed an open
      label trial of moxifloxacin, a fluoroquinolone antibiotic, in patients with
      ankylosing spondylitis. Treatment with moxifloxacin resulted in significant and
      sustained improvement. At 12 weeks, patients treated with moxifloxacin had
      significantly greater improvement in primary outcome measures (P < 0.001). The
      moxifloxacin group also had significantly greater improvement in many of the
      secondary outcome measures (P < 0.001). In this twelve-week trial, moxifloxacin
      was safe, well tolerated, and associated with improvement in the inflammatory
      symptoms of AS.

PMID- 17458396
TI  - A descriptive analysis of authorship within medical journals, 1995-2005.
AB  - INTRODUCTION: The emphasis on publications for promotion in academic medicine
      would lead one to the theory that authorship numbers would increase
      proportionally with this emphasis. To investigate authorship trends across a
      number of periodicals, we performed a descriptive study comparing two full years
      of published articles spaced ten years apart from five medical journals. METHODS:
      Physician reviewers each reviewed all articles of one medical journal for the
      1995 and 2005 publication years. Reviewed journals included Academic Emergency
      Medicine (AEM), Annals of Emergency Medicine (AnnEM), Annals of Internal Medicine
      (AIM), Journal of Trauma (JT), and New England Journal of Medicine (NEJM). Data
      collected for each article were number of authors, ordinal number of the
      corresponding author, type of study described, whether the described study was a
      multicenter trial, whether authorship listed included a "study group," and
      whether any author was also an editor of the journal. RESULTS: A total of 2927
      articles were published in the five journals in 1995, and of these, 1401 (47.9%)
      were analyzed after the exclusion criteria had been applied; for 2005 a total of
      3630 articles were published and of these, 1351 (37.2%) were included in the
      analysis. Across all five journals the mean number of authors per article
      increased from 4.66 to 5.73 between 1995 and 2005 (P < 0.0001), and four of the
      five journals individually had statistically significant increases in the number
      of authors per article. More articles had a journal editor as an author in 2005
      (increased from 7.8% to 11.0%, P = 0.004), though no single journal had a
      statistically significant increase. CONCLUSION: We describe a trend of increasing
      mean authors, editorial authorship, study groups, and multicenter trials over
      time with fewer solo authors now publishing original research or case reports.
      The academic medical community must pursue an authorship requirement consensus to
      assure that a standard of contribution for all authors on a given paper is met.

PMID- 17458397
TI  - Abnormal uterine bleeding.
AB  - Disorders of the menstrual cycle are common problems in ambulatory medicine.
      Abnormal uterine bleeding describes bleeding that is excessive or outside the
      normal menstrual cycle. In the premenopausal woman, the differential diagnosis is
      broad, and pregnancy must always be considered. Determining whether the bleeding
      is ovulatory or anovulatory is a central part of the evaluation, as anovulation
      is one of the most common causes of abnormal uterine bleeding. In patients with
      anovulatory bleeding, the goal of treatment is to minimize blood loss and prevent
      complications from chronic unopposed estrogen. In women with oligomenorrhea or
      amenorrhea, after establishing the etiology, it is necessary to maintain adequate
      estrogen to support bone health. In the peri- and postmenopausal population,
      because the incidence of endometrial hyperplasia and malignancy rises, it is
      important to have a low threshold for endometrial assessment.

PMID- 17458398
TI  - Vitamin D deficiency in the Southern United States.

PMID- 17458399
TI  - Rationale for combination therapy in hypertension management: focus on
      angiotensin receptor blockers and thiazide diuretics.
AB  - Despite recognition that hypertension is a major risk factor for cardiovascular
      events and mortality, blood pressure control rates remain low in the US
      population. Reflecting clinical trial results, hypertension management guidelines
      assert the clinical benefit of achieving current blood pressure goals and
      indicate that most patients will require 2 or more drugs to reach goal. Well
      designed drug combinations counter hypertension via complementary mechanisms that
      increase antihypertensive efficacy, potentially with lower rates of adverse
      events than higher dose monotherapy regimens. Lower adverse event rates, in turn,
      may contribute to greater adherence with treatment. The combination of a low-dose
      diuretic with agents that block the effects of the renin-angiotensin system
      (RAS), such as angiotensin receptor blockers, has been found in numerous clinical
      trials to be highly effective for lowering blood pressure in patients with
      uncomplicated as well as high-risk hypertension, with a comparable favorable side
      effect profile compared with monotherapy. Moreover, agents that block the RAS are
      associated with a lower risk of new-onset diabetes mellitus than other
      antihypertensive classes. Complementary combinations of antihypertensive agents
      provide an efficient and effective approach to hypertension management.

PMID- 17458400
TI  - Pulmonary arterial hypertension: evaluation and management.
AB  - Pulmonary arterial hypertension (PAH), a rare disease involving the pulmonary
      vascular circuit, is defined as an elevation in pulmonary arterial pressures and
      is characterized by symptoms of dyspnea, chest pain, and syncope. If left
      untreated, the disease carries a high mortality rate, with the most common cause
      of death being decompensated right heart failure. Over the past 5 years, there
      have been significant advances in this field in regards to understanding the
      pathogenesis, diagnosis, and classification of PAH. The availability of newer
      drugs has resulted in a radical change in the management of this disease with
      significant improvement in both quality of life and mortality. Ongoing research
      promises to lead to a more comprehensive understanding of the genetics, etiology,
      and pathogenesis of pulmonary arterial hypertension, which may ultimately
      translate into more effective therapeutic options.

PMID- 17458401
TI  - Omeprazole-associated digoxin toxicity.
AB  - Omeprazole is a commonly prescribed inhibitor of the gastric proton pump and has
      numerous indications in the treatment of gastrointestinal diseases. It is
      primarily metabolized through the CYP2C19 enzyme, a member of the P450 mixed
      function oxidase group, although a minor pathway of metabolism is through CYP3A4,
      another P450 enzyme. Digoxin is primarily metabolized outside the P450 system,
      but a minor pathway of metabolism is by CYP3A4. To our knowledge, this is the
      first known case of digoxin toxicity associated with omeprazole. The possible
      pathways for such an interaction are reviewed, including increased stomach
      absorption, p-glycoprotein activity and interactions in the P450 system.

PMID- 17458402
TI  - Primary omental pregnancy on the gastrocolic ligament.
AB  - Omental pregnancy is an extremely rare form of abdominal pregnancy. Only 16 cases
      had been reported in the literature, and most were secondary omental pregnancies.
      We presented a case of primary omental pregnancy located on "gastrocolic
      ligament" diagnosed at surgical operation. The aim of this presentation is to
      remember that pregnancy can exist in unusual localizations, so abdominal
      observation and examination is very important during operations.

PMID- 17458403
TI  - Use of amiodarone in a patient with a shellfish allergy.
AB  - A 65-year-old Caucasian male with a shellfish allergy developed atrial
      fibrillation and hypotension after coronary artery bypass and duodenal ulcer
      surgery. Following electrical cardioversion, oral amiodarone was continued
      chronically without an allergic reaction. There is a common misconception that a
      shellfish allergy correlates to an iodine allergy. There is little documentation
      of the association between an allergy to shellfish and an allergy to iodine. Food
      allergies can be subcategorized based on the involvement of IgE. Upon further
      investigation, it was discovered that shellfish allergies are not due to the
      iodine component, but rather, to a protein found in the shellfish. Amiodarone can
      be safely used in patients with shellfish allergies. A shellfish allergy does not
      necessarily imply an iodine allergy.

PMID- 17458404
TI  - High-riding superior pericardial recess: temporal change can help distinguish
      from mediastinal pathology.
AB  - A high-riding superior pericardial recess is an infrequently encountered normal
      variant which may mimic mediastinal pathology. We present a patient in whom a
      high-riding superior pericardial recess could confidently be diagnosed on a neck
      CT due to its change in size and shape demonstrated on a chest CT which was done
      4 minutes later.

PMID- 17458405
TI  - Ezetimibe-induced acute pancreatitis.
AB  - Ezetimibe is a lipid-lowering agent that inhibits the intestinal absorption of
      cholesterol and other related phytosterols. It is used alone or in combination
      with other lipid-lowering agents in the treatment of various forms of
      hypercholesterolemia. Since its FDA approval in 2002, there are no known
      citations of ezetimibe-induced pancreatitis.

PMID- 17458406
TI  - Complicated inguinal hernia of Amyand.

PMID- 17458407
TI  - Regarding "knowledge, attitudes, and use of emergency contraception among rural
      western North Carolina women".

PMID- 17458408
TI  - Vertebral gout and ambulatory dysfunction.

PMID- 17458409
TI  - Sweet Syndrome associated with erythema nodosum: are they different
      manifestations of the same disease?

PMID- 17458410
TI  - Oxcarbazepine treatment of refractory bipolar illness.

PMID- 17458411
TI  - "But doctor, medicine has changed!".

PMID- 17458412
TI  - Patient's page: facts about abnormal uterine bleeding.

PMID- 17458413
TI  - On forgiveness.

PMID- 17458414
TI  - Is spirituality important to young people in recovery? Insights from participants
      of self-help support groups.

PMID- 17458415
TI  - Case discussion: do not neglect the spiritual history.

PMID- 17458416
TI  - Developmental research on alcohol and spirituality: what we know and what we
      don't know.

PMID- 17458417
TI  - A program of research on spirituality and American Indian alcohol use.
AB  - In this brief report we summarize a pattern of findings that has emerged from our
      research on American Indian (AI) alcohol use and spirituality. With funds from
      the National Institute of Alcohol Abuse and Alcoholism and the Fetzer Institute
      (AA 13 053; P. Spicer, PI) we have used both epidemiologic and ethnographic
      methods to develop a more complete understanding of the role that spirituality
      and religion play in changes in drinking behavior among AIs. We begin by first
      situating the importance of research on spirituality in the more general
      literature on the AI experience with alcohol before highlighting our published
      findings in this area. We then close with some speculation about possible next
      steps in this research program to address what remains one of the most compelling
      sources of health disparities in the first nations of the United States.

PMID- 17458418
TI  - Spirituality and addiction.

PMID- 17458419
TI  - Spirituality and alcoholics anonymous.
AB  - What can be confidently said about AA in general and about the role of
      spirituality in AA in particular? First, there is convincing evidence that
      alcoholism severity predicts later AA attendance. Second, atheists are less
      likely to attend AA, relative to individuals who already hold spiritual and/or
      religious beliefs. However, belief in God before AA attendance does not offer any
      advantage in AA-related benefits, and atheists, once involved, are at no apparent
      disadvantage in deriving AA-related benefits. Third, the spiritually-based
      principles of AA appear to be endorsed in AA meetings regardless of the perceived
      social dynamics or climate of a particular meeting, eg, highly cohesive or
      aggressive. Fourth, significant increases in spiritual and religious beliefs and
      practices seem to occur among AA-exposed individuals. Fifth, in spite of much
      discussion to the contrary there is little evidence that spirituality directly
      accounts for later abstinence. We are finding, however, that spirituality has an
      important indirect effect in predicting later drinking reductions. Specifically,
      in the past 20 years a number of effective methods have been developed to
      facilitate initial AA attendance (AA dropout is high, with some estimates ranging
      as high as 80%). Interventions that lead to initial increases in spirituality
      appear to lead to sustained AA affiliation, which, in turn, produces sustained
      recovery over time.

PMID- 17458420
TI  - Medicine, spirituality, and alcoholics anonymous: a personal story.

PMID- 17458421
TI  - Eye on religion: the Baha'i Faith.

PMID- 17458422
TI  - Helping as healing among recovering alcoholics.
AB  - Several avenues remain open for future research. Perhaps most important,
      experimental research manipulating peer helping activities is needed to confirm
      and extend the conclusions offered here. As suggested previously, the
      correlational evidence linking helping to better recovery outcomes is subject to
      valid critique based on the possibility of third-variable associations, so
      experimental studies manipulating helping are indispensable to demonstrating a
      causal role for peer helping (and to ruling out reverse causality). Future
      research will also be important in identifying what forms of helping work best,
      and when. The Zemore and Kaskutas (2004) study described earlier uncovered some
      rather complex associations between length of recovery and helping in specific
      life domains: longer recovery was positively associated with community-oriented
      helping, negatively associated with recovery-oriented helping (outside of AA
      participation), and not associated with level of life helping. These results hint
      that, over time, recovering alcoholics may naturally transition from helping
      activities associated primarily with alcohol problems to helping activities
      concerned with the broader community--and that there may be some value to this
      transition. What works for a recovering alcoholic early in recovery may not work
      later in recovery. Further research is needed to explore how length of sobriety,
      type of helping, and other variables interact to affect the impact of helping
      activities on recovery outcomes. Another exciting question for further research
      will be why helping helps the helper. It has been suggested that helping enhances
      helpers' self-perceptions of independence, competence, usefulness, and/or social
      status; fosters relationships with others; and diverts helpers from excessive
      self-absorption. Some have argued that helping others contributes to building and
      expressing a positive identity. Cooperation may even be inherently rewarding. A
      recent study found that, when women cooperated (versus competed) in a Prisoner's
      Dilemma game, blood flow increased in areas of their brains rich in dopamine, the
      neurotransmitter involved in reward systems and famed in part for its role in
      addictive behaviors. Moreover, the longer the women engaged in the cooperative
      strategy, the stronger was the activation. The fact that people often compete
      rather than cooperate implies the existence of countervailing tendencies. But,
      the fact that one can (at least sometimes) help oneself by helping others
      suggests that the traditional dualities pitting competition against cooperation,
      and self against other, disguise a compelling third choice. The ability to see
      beyond such dualities may be part of what AA, NA, and other mutual help groups
      offer.

PMID- 17458423
TI  - Meditation and alcohol use.

PMID- 17458424
TI  - On the cover. Mesquite.

PMID- 17458425
TI  - Taming chronic cough.
AB  - OBJECTIVE: To review the available evidence on treating chronic cough to relay a
      thoughtful, evidence-based approach for the diagnosis and treatment of chronic
      cough. DATA SOURCES: MEDLINE, PubMed, EMBASE, and CINAHL were searched using the
      following keywords: cough, asthma, gastroesophageal reflux, sinusitis, rhinitis
      (allergic, seasonal), postnasal drip, vocal cord dysfunction, lung disease
      (interstitial), bronchiectasis, and bronchoscopy. STUDY SELECTION: Studies were
      selected based on their relevance to the diagnosis and treatment of chronic
      cough. Because of a lack of randomized prospective studies, nonrandomized and
      retrospective studies were considered, with their strengths and limitations
      noted. RESULTS: Few randomized controlled trials have addressed the diagnosis and
      treatment of chronic cough. There are several prospective noncontrolled trials
      for adults with chronic cough that found a high percentage of cough resolution
      when using an approach that focused on the diagnosis and treatment of the most
      common causes: asthma, gastroesophageal reflux disease, and upper airway cough
      syndrome. Preliminary studies in children support an approach that distinguishes
      between a wet and dry cough, as well as an in-depth investigation of any specific
      symptoms that point to an underlying chronic illness. CONCLUSION: Allergists, as
      experts in treating upper airway and lower airway disorders, are uniquely poised
      to diagnose and treat chronic cough.

PMID- 17458426
TI  - Clinical efficacy and pharmacokinetic profiles of intranasal and oral cetirizine
      in a repeated allergen challenge model of allergic rhinitis.
AB  - BACKGROUND: Intranasal and oral antihistamines are effective in treating allergic
      rhinitis. Studies comparing these routes of administration of an antihistamine
      regarding efficacy and pharmacokinetic profile are lacking. OBJECTIVE: To compare
      topical and oral routes of administration of cetirizine regarding efficacy,
      plasma exudation, and systemic drug levels in a repeated allergen challenge model
      of allergic rhinitis. METHODS: Oral cetirizine dihydrochloride, 10 mg once daily,
      and topical cetirizine dinitrate in a dose corresponding to 4.4 mg of the
      dihydrochloride salt twice daily were given to grass pollen-sensitive individuals
      for 12 days in a double-blind, placebo-controlled, crossover design. Timothy
      grass pollen allergen challenges were given once daily for 7 days using a nasal
      spray device. Nasal symptoms and peak inspiratory flow were recorded in the
      morning, 10 minutes after allergen challenge, and in the evening. The
      pharmacokinetics of the treatments was monitored in 8 patients. The remaining 28
      patients were challenged topically with histamine 12 and 24 hours after the final
      topical and oral cetirizine doses, respectively. Nasal lavage levels of alpha2
      macroglobulin were determined to evaluate histamine-induced mucosal plasma
      exudation. RESULTS: During the last 3 days of the repeated allergen challenge
      model, chronic symptoms were established. Both treatments reduced symptoms 10
      minutes after allergen challenge (P < .001 vs placebo). Neither treatment reduced
      morning and evening symptoms or nasal peak inspiratory flow. Topical, but not
      oral, cetirizine reduced histamine-induced plasma exudation (P < .01 vs placebo)
      when systemic drug levels were similar in the 2 treatment regimens. CONCLUSIONS:
      Topical and oral cetirizine reduced acute nasal symptoms produced by allergen
      challenges in patients with established chronic symptoms. There were also
      antihistaminic effects of topical cetirizine not related to systemic drug levels.

PMID- 17458427
TI  - Factors influencing patient decisions about the use of asthma controller
      medication.
AB  - BACKGROUND: Patient nonadherence with asthma controller medication is pervasive
      and impedes successful adoption of national treatment guidelines. OBJECTIVE: To
      survey adult patients with asthma about the factors influencing their decisions
      about when to use their asthma controller medications. METHODS: Two hundred
      adults with asthma were randomly selected from a national database and were
      surveyed by telephone about medication use, barriers to adherence, and treatment
      preferences. RESULTS: Adherence to daily controller medication in the group was
      generally well below the prescribed level despite the fact that many had
      relatively severe asthma and inadequately controlled symptoms. Thirty percent of
      the respondents indicated that they had been instructed by their physician to use
      their controller medication intermittently as guided by their symptoms. Most
      respondents expressed a desire to be more in control of their treatment and for
      that treatment to be more immediately effective and long-lasting but did not
      perceive inadequate information to be a barrier to adherence. CONCLUSION: These
      insights into patient perception and motivation suggest the importance of
      developing treatment plans that allow patients some degree of control over
      medication use.

PMID- 17458428
TI  - Tobacco as an allergen in bronchial disease.
AB  - BACKGROUND: Skin testing and sera measurements have verified the existence of
      tobacco specific IgE. However, the few published studies on this matter report
      conflicting results concerning their clinical significance. OBJECTIVE: To verify
      if a specific clinical allergenic response against tobacco might be possible in
      allergenic and nonallergenic bronchial diseases. METHODS: We performed a cross
      sectional observational case-control analysis on 180 patients with asthma,
      chronic obstructive pulmonary disease (COPD), and bronchial carcinoma and
      controls who were randomly chosen. Skin prick tests and serum specific IgE to
      tobacco and related allergens, bronchial challenge with cigarettes and tobacco
      extract, patch tests with tobacco and nicotine, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis immunoblotting, and Enzyme AllergoSorbent Test
      (EAST) inhibition were performed. RESULTS: Twenty-eight patients had positive
      tobacco skin prick test results. The association among positive skin prick test
      results, IgE, and bronchial challenge was strong (P < .001). Tobacco sensitivity
      was higher in patients with pollen asthma than in patients with COPD and
      carcinoma and negative in patients with intrinsic asthma and controls. A positive
      bronchial challenge result was related to the length of habit (P < .001) and the
      tobacco index in patients who had stopped smoking (P < .001). Delayed bronchial
      and patch response was more common in patients with COPD (P < .001). Tobacco IgE
      response (EAST) was related to sensitivity to Lolium perenne (rye grass) pollen
      (P < .001) but not to other vegetables that belong to the Solanaceae family. EAST
      inhibition showed cross-reactivity between tobacco and Lolium pollen.
      CONCLUSIONS: Tobacco may be responsible for a specific IgE response. Patients
      with pollen asthma were those with more positive responses to tobacco due to
      cross-reactivity between Lolium and tobacco allergens.

PMID- 17458429
TI  - Asthma onset and relapse in adult life: the British 1958 birth cohort study.
AB  - BACKGROUND: Few studies have investigated adult-onset wheezing because of
      difficulties identifying childhood asthma or wheeze retrospectively. OBJECTIVE:
      To investigate risk factors for the incidence and recurrence of wheezing illness
      in adulthood. METHODS: British children born during 1 week in 1958 (N = 18,558)
      were followed up periodically. Information on wheezing illness was obtained via
      parental interviews at ages 7, 11, and 16 years and via cohort member interviews
      at ages 23, 33, and 42 years. At ages 44 to 45 years a subset (N = 12,069) was
      targeted for biomedical survey, and total IgE and specific IgE responses to
      grass, cat, and dust mite were measured. RESULTS: Incidences of wheezing illness
      at ages 17 to 33 and 34 to 42 years were positively associated with atopy (any
      specific IgE -0.3 kU/L) and cigarette smoking. For ages 17 to 42 years,
      proportions of incident "asthma" and incident "wheeze without asthma" associated
      with atopy, adjusted for sex and smoking, were estimated to be 34% (95%
      confidence interval [CI], 26%-42%) and 5% (95% CI, 1%-9%), respectively, whereas
      proportions associated with cigarette smoking, adjusted for sex and atopy, were
      estimated to be 13% (95% CI, 0%-26%) and 34% (95% CI, 27%-40%), respectively.
      Among participants with no reported wheezing illness at ages 17 to 23 or 33
      years, wheeze prevalence at the age of 42 years was positively associated with
      symptoms in childhood. CONCLUSIONS: Onset and relapse of wheezing illness in
      adult life seem to be similarly affected by atopy and cigarette smoking, although
      the nature of these effects may differ between asthma and wheeze without asthma.
      Children who apparently "outgrow" early wheezing illness remain at increased risk
      for relapse or recurrence during midlife.

PMID- 17458430
TI  - Food-allergy management from the perspective of restaurant and food establishment
      personnel.
AB  - BACKGROUND: Restaurant and food establishment dining poses dangers for food
      allergic consumers. OBJECTIVE: To identify, from the restaurant's perspective,
      factors that affect providing allergen-safe meals. METHODS: A structured
      questionnaire was administered to a convenience sample of restaurant personnel.
      RESULTS: Participants included 100 individuals (42 managers, 32 servers, 24
      chefs, and 2 others) in 100 establishments (48 restaurants [17 continental, 19
      Asian, and 12 Italian], 18 fast food, and 34 take-out [8 bakery, 13 ice cream, 9
      Asian, and 4 pizza]). Food-allergy training was reported by 42% (76% apprenticing
      and 24% set program). On a 5-point Likert scale, a rating of "very" or "somewhat"
      comfortable was selected by 72% for providing a safe meal, 70% for "guaranteeing"
      a safe meal, and 47% for managing a food-allergy emergency. Regarding knowledge
      questions, 24% indicated that consuming a small amount of allergen would be safe,
      35% believed that fryer heat would destroy allergens, 54% considered a buffet
      safe if kept "clean," and 25% thought that removing an allergen from a finished
      meal (eg, taking off nuts) was safe. More than 80% recognized peanut, milk, and
      seafood as major allergens (61% recognized egg). In practice, 58% indicated
      having a plan in place in the event of a reaction, and 62% had a plan to provide
      safe meals. An interest in further training was expressed by 61% of participants.
      CONCLUSIONS: The restaurant personnel surveyed expressed a relatively high
      comfort level in providing safe meals to allergic consumers, but there are
      deficits in their knowledge base, indicating the need for more training and
      consumer caution.

PMID- 17458431
TI  - The use of raw or boiled crustacean extracts for the diagnosis of seafood
      allergic individuals.
AB  - BACKGROUND: Seafood plays an important role in human nutrition and is responsible
      for severe hypersensitivity reactions. OBJECTIVE: To evaluate how the cooking
      process may alter the in vivo and in vitro allergenicity of these extracts.
      METHODS: Raw and boiled extracts of shrimps and 2 types of lobsters were
      manufactured. Boiled extracts were prepared after the raw material was boiled for
      15 minutes in phosphate-buffered saline. Raw and boiled extracts were homogenized
      and extracted for 4 hours. Afterward, the extracts were centrifuged, dialyzed,
      filtered, and freeze-dried. Seventy-eight patients were skin prick tested with
      these raw and boiled extracts. Specific IgE against the 6 extracts was measured
      by enzyme-linked immunosorbent assay (ELISA). Immunoblots and ELISA inhibition
      studies were performed with a pool of sera. RESULTS: In vivo results showed that
      boiled extracts induced statistically significant larger wheals than raw
      extracts. More patients with positive results were also detected with boiled
      extracts. In vitro experiments by direct ELISA confirmed the in vivo results. The
      protein content in the boiled extracts decreased, and important differences were
      detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cross
      reactivity experiments showed that both types of extracts retained similar
      allergenic characteristics, even if the immunoblots revealed some differences in
      IgE binding. CONCLUSIONS: More patients were identified using boiled extracts of
      shrimp and American and spiny lobsters than with raw extracts. The wheal sizes of
      the skin test reactions and specific IgE levels were also significantly greater
      using boiled extracts. The use of boiled extracts seems to be more effective in
      diagnosing seafood allergy.

PMID- 17458432
TI  - Penicillin skin testing in patients with a history of beta-lactam allergy.
AB  - BACKGROUND: Vancomycin and fluoroquinolones are commonly used in patients with a
      history of penicillin allergy. OBJECTIVE: To determine the safety and utility of
      penicillin skin testing (PST). METHODS: Retrospective study of patients with a
      history of penicillin allergy between April 1, 1999, and September 30, 2004.
      Penicillin skin testing was performed by means of standard methods using
      benzylpenicilloyl-polysine, penicillin G, and histamine and saline controls.
      RESULTS: Of 596 patients studied, 25.3% were outpatients, 50.3% were inpatients,
      and 24.3% were intensive care unit patients. The most common antibiotics used
      during the time of PST were vancomycin and fluoroquinolones. Results of PST were
      negative in 88.4% of patients, positive in 8.2%, and indeterminate in 3.4%. One
      patient (0.17%) developed urticaria immediately after PST. Fifty-five percent of
      patients with negative PST results were changed to a beta-lactam drug, more
      frequently in the intensive care unit vs the outpatient setting (70.3% vs 8.6%; P
      < .001) and in adults vs patients younger than 18 years (58.6% vs 8.1%; P <
      .001). A beta-lactam antibiotic was used in 290 patients with negative PST
      results. Of the patients given beta-lactam antibiotics, 5 (1.7%) had adverse
      reactions: 2 had hives after 16 and 20 days of therapy, 1 had a nonspecific rash
      after 17 days of therapy, 1 had flushing and urticaria 3 hours after a test dose
      of piperacillin-tazobactam, and 1 had a pruritic rash after 12 hours of therapy.
      CONCLUSIONS: Patients with a history of penicillin allergy can safely use beta
      lactam drugs if negative PST results.

PMID- 17458433
TI  - National study of US emergency department visits for acute allergic reactions,
      1993 to 2004.
AB  - BACKGROUND: The clinical epidemiology of acute allergic reactions in the
      emergency department (ED) is uncertain. OBJECTIVES: To characterize ED visits for
      acute allergic reactions and to evaluate national trends in ED management.
      METHODS: The National Hospital Ambulatory Medical Care Survey was used to
      identify a nationally representative sample of ED visits between 1993 and 2004.
      Cases with a diagnosis of acute allergic reaction were identified by
      International Classification of Diseases, Ninth Revision (ICD-9) codes (9950,
      9951, 9952, 9953, 9956). RESULTS: A total of 12.4 million allergy-related ED
      visits occurred from 1993 to 2004, representing 1.0% (95% confidence interval,
      0.93%-1.10%) of all ED visits or 1.03 million ED visits per year. The number of
      allergy-related ED visits remained relatively stable, averaging 3.8 per 1,000 US
      population per year (95% confidence interval, 3.4-4.1; P for trend = .39).
      Although 63% of all visits were coded as urgent, only 4% required
      hospitalization. Anaphylaxis coding was rare (1%). ED staff prescribed
      medications in 87% of visits, especially histamine, blockers (62%; P for trend =
      .29). Increases were noted from 1993 to 2004 for corticosteroids (22% to 50%; P <
      .001), histamine2 blockers (7% to 18%; P < .001), and inhaled beta-agonists (2%
      to 6%; P = .008). Epinephrine use was infrequent and declining (19% to 7%; P =
      .04). CONCLUSION: Between 1993 and 2004, significant variability has occurred in
      ED management of acute allergic reactions.

PMID- 17458434
TI  - Sublingual immunotherapy in sensitized mice.
AB  - BACKGROUND: Many studies have demonstrated immunologic changes induced by
      sublingual immunotherapy (SLIT), but the definitive mechanism of action needs
      further investigation. OBJECTIVE: To study the immunologic response induced by
      SLIT in sensitized mice. METHODS: Timothy grass (Phleum pratense)-sensitized mice
      received SLIT for 2, 4, or 6 weeks at 3 different concentrations, including a
      buffer control. Serum samples and washes of the lungs (bronchoalveolar lavage
      [BAL]) and the nasal passages (nasal lavage [NAL]) were analyzed for allergen
      specific antibodies. T cells were isolated from the spleen and cervical lymph
      nodes for the analysis of proliferation and cytokine production. RESULTS:
      Sublingual immunotherapy in sensitized mice resulted in a 30-fold increase in
      antigen specific IgA levels in BAL and NAL fluid compared with buffer-treated
      mice, whereas antigen specific IgE was undetectable in BAL and NAL fluid in
      animals treated with SLIT. Furthermore, IgA levels were proportional to the dose
      and duration of SLIT. Levels of specific IgA in serum correlated with levels in
      BAL and NAL fluid. Serum IgA levels were proportional to the duration of allergen
      exposure to the oral mucosa. Conversely, no changes in serum levels of IgE and
      IgG were induced by SLIT. Proliferation of T cells was increased in mice treated
      with SLIT compared with nontreated mice. CONCLUSION: High levels of IgA in serum
      and in BAL and NAL fluid of mice treated with SLIT demonstrate that SLIT induces
      a mucosal, nonallergic response in sensitized mice.

PMID- 17458435
TI  - Use of granulocyte-macrophage colony-stimulating factor to reverse anergy in
      otherwise immunologically healthy children.
AB  - BACKGROUND: T-cell anergy, as measured by delayed hypersensitivity skin testing,
      is associated with increased susceptibility to infection. Because the repertoire
      of effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) includes
      enhancement of antigen processing and presentation by antigen-presenting cells,
      GM-CSF has been used to augment immune function in human immunodeficiency virus
      induced and other viral illness-induced immune dysfunction and to affect
      positively immune function in a wide variety of disorders. OBJECTIVE: To attempt
      reversal of T-cell anergy using GM-CSF in 3 otherwise immunologically healthy
      children with severe recurrent and persistent viral respiratory tract infections
      and in one child with recurrent bacterial sepsis. METHODS: After written informed
      consent and baseline data were obtained, the study participants were administered
      3 two-week cycles of GM-CSF. Delayed hypersensitivity skin testing and laboratory
      tests were repeated 2 weeks after the third cycle and subsequently as clinically
      indicated. RESULTS: All 4 children developed delayed hypersensitivity by skin
      testing, and all demonstrated markedly decreased number and severity of
      infection. Improvement persisted in all patients for at least 1 year. A single
      cycle of additional treatment in 2 patients reestablished delayed
      hypersensitivity and decreased infection, both of which persisted throughout the
      follow-up period of 4 or more years. CONCLUSIONS: GM-CSF treatment reversed T
      cell anergy in 4 children. Reestablishment of delayed hypersensitivity was
      associated with a significant decrease in infection. Although further studies
      will be needed, use of GM-CSF should be considered as an immune modulator in
      patients with T-cell anergy and recurrent infections.

PMID- 17458436
TI  - Fresh frozen plasma for the treatment of hereditary angioedema.
AB  - BACKGROUND: Fresh frozen plasma (FFP) has been used as a treatment option for
      patients with hereditary angioedema (HAE) because it contains Cl esterase
      inhibitor, and alternate therapies are not yet available in the United States.
      However, because FFP also contains other substrates, it has been hypothesized to
      have the potential to worsen or precipitate an acute attack of HAE. OBJECTIVE: To
      research patient records and the medical literature to determine whether FFP can
      exacerbate symptoms or precipitate an attack of HAE. METHODS: The following
      keywords were searched in PubMed and OVID: hereditary angioedema, angioedema and
      fresh frozen plasma, angioedema and FFP, and hereditary angioneurotic edema.
      English-language articles were searched from 1966 to the present. Also, after
      institutional review board approval, the medical records of patients with HAE at
      our institution who have received FFP since 1990 were reviewed to determine if
      there was evidence that FFP exacerbated the symptoms of HAE. RESULTS: The English
      language literature review and our patient medical record review failed to
      identify instances when FFP exacerbated symptoms of HAE or precipitated an
      attack. Several reports and our experience suggest that FFP is an effective
      prophylactic agent before surgery and for treatment of acute HAE attacks without
      evidence of exacerbation or initiation of symptoms. CONCLUSIONS: FFP seems to be
      safe and effective in preventing exacerbations of HAE before surgery and for
      acute exacerbations of HAE without evidence of it initiating an attack or
      worsening a preexisting attack.

PMID- 17458437
TI  - Hyperimmunoglobulinemia E syndrome associated with coronary artery aneurysms:
      deficiency of central memory CD4+ T cells and expansion of effector memory CD4+ T
      cells.
AB  - BACKGROUND: Hyperimmunoglobulinemia E syndrome is a primary immunodeficiency
      disorder characterized by elevated IgE levels, recurrent infections, pruritic
      rash, and skeletal and dental abnormalities. Autosomal dominant, autosomal
      recessive, and sporadic forms have been described. Coronary artery aneurysms and
      analysis of central (TCMs) and effector (TEMs) memory T cells have not been
      previously reported with this syndrome. OBJECTIVE: To describe a 30-year-old
      woman with hyperimmunoglobulinemia E syndrome who was found to have coronary
      artery aneurysms, deficiency in CD4+ TCMs, and expansion of CD4+ TEMs expressing
      CD45RA antigen (TEMRAs). METHODS: The patient presented to the clinic after
      hospitalization for chest pain. Coronary angiogram performed during the
      hospitalization revealed aneurysms in multiple coronary arteries with thrombus
      formation. In addition, she had a history of recurrent pneumonia, staphylococcal
      skin abscesses, and a pruritic facial rash. An extensive immunologic evaluation
      was performed. RESULTS: Immunologic studies revealed increased serum IgE levels
      (13,434 IU/dL), decreased proliferative responses to the soluble recall antigens
      tetanus toxoid and Candida albicans, and normal responses to mitogens. Analysis
      of lymphocyte subsets showed a deficiency of CD4+ TEMs and an increase in CD4+
      TEMRAs. In addition, a decreased proportion and number of memory B cells and a
      deficiency in antibody response to pneumococcal antigens were observed.
      CONCLUSION: Hyperimmunoglobulinemia E syndrome may be associated with coronary
      artery aneurysms and with deficiency in CD4+ TEMs and expansion of CD4+ TEMRAs.
      Comprehensive immunologic evaluation should be performed in patients with this
      syndrome.

PMID- 17458438
TI  - Food allergy to Paracentrotus lividus (sea urchin roe).
AB  - BACKGROUND: Sea urchins are increasingly used as culinary products in Japanese
      and Korean cuisine throughout the world. OBJECTIVE: To investigate a possible IgE
      mediated allergy in a patient who experienced an anaphylactic reaction after
      eating sea urchin roe and mussels. PATIENT AND METHODS: A 40-year-old man
      experienced generalized pruritus and urticaria, shortness of breath, and wheezing
      10 minutes after eating steamed mussels and boiled sea urchin roe. Investigations
      included skin prick tests, serum specific IgE determinations, oral challenge
      tests, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and
      immunoblotting. RESULTS: Results of skin prick tests with common aeroallergens
      were negative. Positive prick test responses were obtained with boiled and raw
      sea urchin extracts, boiled and raw sea urchins themselves, and boiled sea urchin
      water. Results of an oral challenge test with steamed mussels were negative. Five
      minutes after the oral mucosa contacted the boiled sea urchin extract, lip
      pruritus was present. Specific IgE concentrations to boiled sea urchin water and
      boiled and raw sea urchins surpassed the criterion for a positive result (1.1,
      0.6, and 0.4 kU/L, respectively). In boiled sea urchin extract, a 118-kDa band
      appeared as the unique relevant IgE-binding antigen. CONCLUSION: In this patient
      with IgE-mediated food allergy to sea urchin roe, a 118-kDa protein seemed to be
      the antigen responsible for the reaction.

PMID- 17458439
TI  - Hereditary angioedema presenting in late middle age after angiotensin-converting
      enzyme inhibitor treatment.
AB  - BACKGROUND: Angioedema due to Cl esterase inhibitor (CI-INH) deficiency may be
      hereditary (HAE), commonly first occurring in childhood, or acquired (AAE), with
      onset usually in middle age. Type I HAE exhibits low levels of functionally
      normal C1-INH. Dysfunctional Cl-INH typifies type II HAE. Patients with type I
      AAE have low levels of Cl-INH, Clq complement, and C4 complement. In type II AAE,
      there is immune blockade of C1-INH. OBJECTIVE: To describe a man who first
      presented at the age of 52 years with type I HAE triggered by the administration
      of an angiotensin-converting enzyme (ACE) inhibitor. METHODS: The patient had C1
      INH levels, a complement profile, and a lack of underlying co-pathology that led
      to the diagnosis of type I HAE triggered by the administration of an ACE
      inhibitor. RESULTS: The patient presented with life-threatening angioedema. His
      C4 complement and Cl-INH serum levels were below the reference ranges, and his C3
      complement, total hemolytic complement assay, and Clq complement levels remained
      within the reference ranges. During the 10 years between his initial episode of
      angioedema and the second, he had not developed any secondary medical conditions,
      and he had been taking the ACE inhibitor lisinopril for 7 years. CONCLUSION:
      Physicians must remain aware of the possibility of unmasking HAE in the adult and
      geriatric population with the common use of ACE inhibitors for the treatment of
      hypertension, cardiovascular diseases, and metabolic diseases.

PMID- 17458440
TI  - A case of food allergy due to longan fruit.

PMID- 17458441
TI  - Jumping to conclusions: a network model predicts schizophrenic patients'
      performance on a probabilistic reasoning task.
AB  - This article extends computational models of schizophrenia that focus on the
      negative aspects of this syndrome to behavioral biases that are associated with a
      positive symptom of schizophrenia, namely delusions. The phenomenon studied is
      the "jump-to-conclusions" style of reasoning that is characterized by delusional
      patients--in comparison with controls--whereby they make less-informed decisions
      when an option to collect more decision-specific information is available.
      Simulations show that these differences can be mimicked by modulating the gain
      parameter-associated with variations in dopamine level-in a simple network model.

PMID- 17458442
TI  - Intact emotion-induced recognition bias in neuropsychological patients with
      executive control deficits.
AB  - In recognition memory tasks, emotionally negative words are judged more often as
      "old" relative to emotionally neutral words, suggesting a shift in response bias.
      We wondered whether this bias shift was due to the flexible regulation of
      executive control during memory retrieval. To address this question, we
      investigated individuals with high variability in executive control functions. As
      expected, we observed that emotional word meaning did indeed have a strong
      influence on the bias toward responding "old," independent of recognition
      accuracy and overall response bias. However, these effects were uncorrelated with
      executive control, as measured by the Trail Making Test, and were fully intact,
      even in a sample of hospitalized neurological patients with severe executive
      dysfunctions, some of whom had marked damage in fronto-thalamo-striatal networks.
      Having concluded that the emotion-induced bias must develop on different grounds,
      we went on to discuss alternative explanations.

PMID- 17458443
TI  - Affective guidance in the Iowa gambling task.
AB  - It has been suggested that affective states can guide higher level cognitive
      processes and that such affective guidance may be particularly important when
      real-life decisions are made under uncertainty. We ask whether affect guides
      decisions in a laboratory task that models real-life decisions under uncertainty.
      In the Iowa gambling task (IGT), participants search for monetary payoffs in an
      uncertain environment. Recent evidence against an affective guidance
      interpretation of the IGT indicates a need to set a standard for what counts as
      evidence of affective guidance. We present a novel analysis of IGT, and our
      results show that participants' galvanic skin response (GSR) reflects an
      affective process that precedes and guides cognition. Specifically, prior to
      participants' knowledge of the optimal strategy, their GSRs are significantly
      higher when they are about to select from a bad deck, relative to a good deck,
      and this difference in GSR is correlated with a behavioral preference for the
      good deck.

PMID- 17458444
TI  - Reappraisal modulates the electrocortical response to unpleasant pictures.
AB  - Cognitive strategies such as reappraisal reduce the intensity of negative
      experience and brain activity that is sensitive to emotional salience. The time
      course of reappraisal-related neural modulation remains unclear, and it is
      unknown whether the electrocortical response to emotional stimuli is sensitive to
      reappraisal. Event-related brain potentials were recorded first while
      participants passively viewed pleasant, unpleasant, and neutral pictures, and
      then during an emotion regulation block in which participants were instructed to
      attend to or reappraise unpleasant pictures. The late positive potential (LPP)
      was enhanced for pleasant and unpleasant pictures in the passive viewing block,
      and reappraisal resulted in a reliably reduced LPP--a protracted modulation that
      began 200 msec after stimulus onset. The degree of LPP modulation was positively
      related to reductions in the self-reported emotional intensity that followed
      emotion regulation instructions. These results indicate that reappraisal
      modulates early electrocortical activity that is related to emotional salience,
      and that the LPP is a useful tool for studying emotion regulation.

PMID- 17458445
TI  - Does incongruence of lexicosemantic and prosodic information cause discernible
      cognitive conflict?
AB  - We are often required to interpret discordant emotional signals. Whereas
      equivalent cognitive paradigms cause noticeable conflict via their behavioral and
      psychophysiological effects, the same may not necessarily be true for discordant
      emotions. Skin conductance responses (SCRs) and heart rates (HRs) were measured
      during a classic Stroop task and one in which the emotions conveyed by
      lexicosemantic content and prosody were congruent or incongruent. The
      participants' task was to identify the emotion conveyed by lexicosemantic content
      or prosody. No relationship was observed between HR and congruence. SCR was
      higher during incongruent than during congruent conditions of the experimental
      task (as well as in the classic Stroop task), but no difference in SCR was
      observed in a comparison between congruence effects during lexicosemantic emotion
      identification and those during prosodic emotion identification. It is concluded
      that incongruence between lexicosemantic and prosodic emotion does cause notable
      cognitive conflict. Functional neuroanatomic implications are discussed.

PMID- 17458446
TI  - Effects of emotion on item and source memory in young and older adults.
AB  - Emotional experiences are easier to remember than neutral ones, but whether
      memory for all aspects of an experience is improved by emotion remains unclear.
      Some researchers have argued that the influence of emotion on memory is different
      for item than for source information, whereas others have argued that emotion
      affects both similarly. Also, whether item and source memory are affected by
      emotion in older people in the same way as in young people is currently unclear.
      We examined item and source memory for emotional and neutral materials in young
      and older adults. Memory for emotional items was superior to memory for neutral
      items, whereas there was no difference in source memory. Overall, item and source
      memory were poorer in older people than in young people, but emotion seemed to
      have a similar effect on both age groups. Although emotional content was
      remembered better than neutral content, this benefit did not apply to source
      memory. However, varying the emotionality of the source (i.e., the voice in
      Experiment 3) improved memory for the source, and this effect was greater in
      young than in older people. Tone of voice had no effect on item memory in older
      people, but the effect was variable in the young and may depend on the extent to
      which the tone of voice moderates the interpretation of the content.

PMID- 17458447
TI  - Motion in the mind's eye: comparing mental and visual rotation.
AB  - Mental rotation is among the most widely studied visuospatial skills in humans.
      The processes involved in mental rotation have been described as analogous to
      seeing an object physically rotate. We used functional magnetic resonance imaging
      of the whole brain and localized motion-sensitive hV5/MT+ to compare brain
      activation for stimuli when they were mentally or visually rotated. The results
      provided clear evidence for activation in hV5/MT+ during both mental and visual
      rotation of figures, with increased activation for larger rotations. Combined
      with the overall similarities between mental and visual rotation in this study,
      these results suggest that mental rotation recruits many of the same neural
      substrates as observing motion.

PMID- 17458448
TI  - Supported spirituality: a new frontier in the recovery-oriented mental health
      system.

PMID- 17458449
TI  - Integrating religion and spirituality in mental health: the promise and the
      challenge.
AB  - Today's mental health system is largely a product of western science. Like a one
      eyed giant, it has great power, but it lacks the wisdom which makes life sacred
      and meaningful. The challenge for today's mental health system is to unite East
      and West; to integrate wisdom and science; to make room for the sacred as well as
      the practical. One of the most critical domains for integration-and one of the
      most difficult to address-is the area of religion and spirituality. The purpose
      of this paper is to review the historical tension concerning the integration of
      religion and the science of mental health; to explore current social trends that
      are creating new opportunities and pressures to move in this direction; and to
      discuss strategies for the integration of religion and spirituality in mental
      health services and practice.

PMID- 17458450
TI  - Spirituality and religion in recovery: some current issues.
AB  - This paper addresses current perspectives on the roles of spirituality and
      religion in recovery from serious mental health problems. Drawing on a variety of
      discussion groups and consultations in addition to the published literature,
      consumer perceptions as well as those of mental health and religious
      professionals are reviewed. Consumers note both potentially supportive and
      burdensome roles of religion and spirituality in recovery. Professionals report
      both hope for, and discomfort with, these domains in the context of mental health
      services. From each perspective emerge key recommendations regarding the
      appropriate place of spirituality and religion in psychiatric rehabilitation and
      related supports.

PMID- 17458451
TI  - Personal perspectives about the meaning of religion and spirituality among
      persons with serious mental illnesses.
AB  - This paper examines the various meanings persons with serious mental illnesses
      attribute to the concepts of religion and spirituality. In-depth semi-structured
      interviews were conducted with forty individuals with serious mental illnesses
      who have incorporated alternative healing practices into their recovery process.
      The qualitative data analysis revealed that study participants differentially
      defined religion and spirituality using two sets of descriptors: (a) core
      characteristics describing the nature of each concept, and (b) functional
      characteristics describing the impact of religion and spirituality on the
      individual. Implications for clinical practice and future research on the role of
      religion and spirituality in recovery are discussed.

PMID- 17458452
TI  - Relevance of spirituality for people with mental illness attending consumer
      centered services.
AB  - Spirituality has been cited in the literature as having a positive effect on
      mental health outcomes. This paper explores the relationship of spirituality to
      demographic, psychiatric illness history and psychological constructs for people
      with mental illness (N=1835) involved in consumer-centered services (CCS
      Clubhouses and Consumer run drop-in centers). Descriptive statistics indicate
      that spirituality is important for at least two thirds of the members in the
      study. Members primarily indicated participation in public spiritual activities
      (i.e., church, bible study groups), followed by private activities (prayer,
      reading the bible, and meditation) (both of which were centered on belief in the
      transcendent). A logistic regression analysis was done to explore variables
      related to spirituality (i.e., demographics, psychiatric illness history, and
      psychological constructs). Results suggest that age, gender, having psychotic
      symptoms, having depressive symptoms, and having a higher global quality of life,
      hope and sense of community were all significant correlates of spirituality.

PMID- 17458453
TI  - Spirituality and psychosocial rehabilitation: empowering persons with serious
      psychiatric disabilities at an inner-city community program.
AB  - Of 48 persons in a psychosocial rehabilitation program, 20 participated in an
      optional spirituality group (SG), while the other 28 did not. The recovery
      progress based on treatment goal attainment is compared between those
      participating and those not participating in the SG. Within 6 months, all of the
      SG participants (ioo%) achieved their goals, compared to 16 of the 28 individuals
      (57%) not in the SG. The difference between the two groups is statistically
      significant. The role that spirituality played in the SG participants' recovery
      process is discussed in light of their self-reports.

PMID- 17458454
TI  - Gilead revisited: faith and recovery.
AB  - The role of spirituality in recovery from mental illness has gained increased
      attention in recent years. In this article, the authors present an update on
      previous work exploring the role and function of religion/spirituality in the
      lives of people participating in a psychiatric rehabilitation program (Bussema &
      Bussema, 2000). Fifty-eight (58) participants age 18 to 64 completed a
      spirituality survey based on Pargament's five coping functions of religion. Chi
      square tests for independence and independent groups t-tests were performed.
      Seventy-one percent of the respondents reported that their spiritual life has
      played a significant role in their recovery. Reported religious coping strategies
      are discussed within the framework of a recovery model of service delivery.

PMID- 17458455
TI  - Spirituality matters: creating a time and place for hope.
AB  - Individuals with serious psychiatric disabilities may become demoralized or
      hopeless consequent to longstanding disability and stigma. Potential antidotes
      are social support from the religious community and use of personal spiritual
      resources as coping mechanisms. The "Spirituality Matters Group" offers comfort
      and hope through structured and innovative exercises focusing on spiritual
      beliefs and coping. Activities facilitate verbal expression and appropriate
      social interaction, and build a sense of community. Activities and themes from
      selected group sessions are discussed within a recovery-oriented "emotion-focused
      coping" framework.

PMID- 17458456
TI  - My journey of spirituality and resilience.

PMID- 17458457
TI  - Journey of my mind: a story of recovery.

PMID- 17458458
TI  - Mental health ministries.

PMID- 17458459
TI  - Analysis of trace elements and ions in ambient fine particulate matter at three
      elementary schools in Ohio.
AB  - The results from a chemical characterization study of fine particulate matter
      (PM2.5) measured at three elementary schools in Central and Southeast Ohio is
      presented here. PM2.5 aerosol samples were collected from outdoor monitors and
      indoor samplers at each monitoring location during the period of February 1,
      1999, through August 31, 2000. The locations included a rural elementary school
      in Athens, OH, and two urban schools within Columbus, OH. The trace metal and
      ionic concentrations in the collected samples were analyzed using an X-ray
      fluorescence spectrophotometer and ion chromatography unit, respectively. Sulfate
      ion was found to be the largest component present in the samples at all three of
      the sites. Other abundant components included nitrate, chloride, ammonium, and
      sodium ions, as well as calcium, silicon, and iron. The average PM2.5
      concentrations showed similar temporal variations among the three sites within
      the study region. PM2.5 and its major component, sulfate ion, showed strong
      seasonal variations with maximum concentrations observed during the summer at all
      three of the sites. The indoor environment was found to be more contaminated
      during the spring months (March through May) at New Albany (a suburb of Columbus,
      OH) and East Athens (rural Ohio area). Potential source contribution function
      analysis showed that particulate matter levels at the monitoring sites were
      affected by transport from adjoining urban areas and industrial complexes located
      along the Ohio River Valley. A preliminary outdoor source apportionment using the
      principal component analysis (PCA) technique was performed. The results from the
      PCA suggest that the study region was primarily impacted by industrial, fossil
      fuel combustion, and geological sources. The 2002 emissions inventory data for
      PM2.5 compiled by Ohio Environmental Protection Agency also showed impacts of
      similar source types, and this was used to validate the PCA analysis.

PMID- 17458460
TI  - Source apportionment of fine particles in Tennessee using a source-oriented
      model.
AB  - Source apportionment of fine particles (PM2.5, particulate matter < 2 microm in
      aerodynamic diameter) is important to identify the source categories that are
      responsible for the concentrations observed at a particular receptor. Although
      receptor models have been used to do source apportionment, they do not fully take
      into account the chemical reactions (including photochemical reactions) involved
      in the formation of secondary fine particles. Secondary fine particles are formed
      from photochemical and other reactions involving precursor gases, such as sulfur
      dioxide, oxides of nitrogen, ammonia, and volatile organic compounds. This paper
      presents the results of modeling work aimed at developing a source apportionment
      of primary and secondary PM2.5. On-road mobile source and point source
      inventories for the state of Tennessee were estimated and compiled. The national
      emissions inventory for the year 1999 was used for the other states. U.S.
      Environmental Protection Agency Models3/Community Multi-Scale Air Quality
      modeling system was used for the photochemical/secondary particulate matter
      modeling. The modeling domain consisted of a nested 36-12-4-km domain. The 4-km
      domain covered the entire state of Tennessee. The episode chosen for the modeling
      runs was August 29 to September 9, 1999. This paper presents the approach used
      and the results from the modeling and attempts to quantify the contribution of
      major source categories, such as the on-road mobile sources (including the
      fugitive dust component) and coal-fired power plants, to observed PM2.5
      concentrations in Tennessee. The results of this work will be helpful in policy
      issues targeted at designing control strategies to meet the PM2.5 National
      Ambient Air Quality Standards in Tennessee.

PMID- 17458461
TI  - Sensitivity analysis and evaluation of MicroFacPM: a microscale motor vehicle
      emission factor model for particulate matter emissions.
AB  - A microscale emission factor model (MicroFacPM) for predicting real-time site
      specific motor vehicle particulate matter emissions was presented in the
      companion paper titled "Development of a Microscale Emission Factor Model for
      Particulate Matter (MicroFacPM) for Predicting Real-Time Motor Vehicle
      Emissions". The emission rates discussed are in mass per unit distance with the
      model providing estimates of fine particulate matter (PM2.5) and coarse
      particulate matter. This paper complements the companion paper by presenting a
      sensitivity analysis of the model to input variables and evaluation model outputs
      using data from limited field studies. The sensitivity analysis has shown that
      MicroFacPM emission estimates are very sensitive to vehicle fleet composition,
      speed, and the percentage of high-emitting vehicles. The vehicle fleet
      composition can affect fleet emission rates from 8 mg/mi to 1215 mg/mi; an
      increase of 5% in the smoking (high-emitting) current average U.S. light-duty
      vehicle fleet (compared with 0%) increased PM2.5 emission rates by -272% for
      2000; and for the current U.S. fleet, PM2.5 emission rates are reduced by a
      factor of -0.64 for speeds >50 miles per hour (mph) relative to a speed of 10
      mph. MicroFacPM can also be applied to examine the contribution of emission rates
      per vehicle class, model year, and sources of PM. The model evaluation is
      presented for the Tuscarora Mountain Tunnel, Pennsylvania Turnpike, PA, and some
      limited evaluations at two locations: Sepulveda Tunnel, Los Angeles, CA, and Van
      Nuys Tunnel, Van Nuys, CA. In general, the performance of MicroFacPM has shown
      very encouraging results.

PMID- 17458462
TI  - Characterization of PM2.5 aerosols dominated by local pollution and Asian dust
      observed at an urban site in Korea during aerosol characterization experiments
      (ACE)--Asia Project.
AB  - Daily fine particulate matter (PM2.5) samples were collected at Gwangju, Korea,
      during the Aerosol Characterization Experiments (ACE)-Asia Project to determine
      the chemical properties of PM2.5 originating from local pollution and Asian dust
      (AD) storms. During the study period, two significant events occurred on April 10
      13 and 24-25, 2001, and a minor event occurred on April 19, 2001. Based on air
      mass transport pathways identified by back-trajectory calculation, the PM2.5
      dataset was classified into three types of aerosol populations: local pollution
      and two AD aerosol types. The two AD types were transported along different
      pathways. One originated from Gobi desert area in Mongolia, passing through
      Hunshandake desert in Northern Inner Mongolia, urban and polluted regions of
      China (AD1), and the other originated in sandy deserts located in the Northeast
      Inner Mongolia Plateau and then flowed southward through the Korean peninsula
      (AD2). During the AD2 event, a smoke plume that originated in North Korea was
      transported to our study site. Mass balance closures show that crustal materials
      were the most significant species during both AD events, contributing -48% to the
      PM2.5 mass; sulfate aerosols (19.1%) and organic matter (OM; 24.6%) were the
      second greatest contributors during the AD1 and AD2 periods, respectively,
      indicating that aerosol properties were dependent on the transport pathway. The
      sulfate concentration constituted only 6.4% (4.5 microg/m3) of the AD2 PM2.5
      mass. OM was the major chemical species in the local pollution-dominated PM2.5
      aerosols, accounting for 28.7% of the measured PM2.5 mass, followed by sulfate
      (21.4%), nitrate (15%), ammonium (12.8%), elemental carbon (8.9%), and crustal
      material (6.5%). Together with substantial enhancement of the crustal elements
      (Mg, Al, K, Ca, Sc, Ti, Mn, Fe, Sr, Zr, Ba, and Ce), higher concentrations of
      pollution elements (S, V, Ni, Zn, As, Cd, and Pb) were observed during AD1 and
      AD2 than during the local pollution period, indicating that, in addition to
      crustal material, the AD dust storms also had a significant influence on
      anthropogenic elements.

PMID- 17458463
TI  - Development of cleaner-burning brick kilns in Ciudad Juarez, Chihuahua, Mexico.
AB  - The following results provide a comparison between net airborne contamination
      produced by the traditional form of kiln used in Northern Mexico and by those
      modified according to a design by Dr. Robert Marquez. What has become known as
      the MK style kiln was intended to significantly reduce contaminant emissions. The
      concept involves covering the kiln with a dome and channeling the output of an
      active kiln through a second, identical loaded kiln for its additional filtration
      of the effluents. Kilns of a pair are connected via clay brick channels. The
      roles are reversed after the initial kiln is refilled. Significant reductions in
      the particulate and gaseous emissions were achieved in the prototype system, but
      a connectional problem with recent kiln pairs has also limited the degree of
      operational success. The problem did not mask the potential of the MK kiln, as
      will be shown. Additional anticipated benefits to the owners of MK kilns, such as
      reduced operating cycles and decreased quantities of fuel, also have been
      verified. Key measurements made during all of the burns were of aerosol densities
      and buoyancies in the flues, kiln temperatures, and, on a number of occasions,
      chemical analyses of both aerosol and gaseous effluents. Continuous time
      histories of aerosol densities for most burns (of a total of -40) provide a basis
      for examining features and the effects of differing styles of operation with
      respect to burn efficiency and net contaminant masses. Covering the active kiln
      with a dome produces a net reduction in dry aerosol effluent mass of a factor
      between 5 and 10, whereas the addition of a filter kiln produces a net reduction
      of about a factor of 2. The use of used motor oil as a fuel further reduced
      aerosol contamination by -1 order of magnitude.

PMID- 17458464
TI  - Effects of burnings of wax apple stubble and rice straw on polychlorinated
      dibenzo-p-dioxin and dibenzofuran concentrations in air and soil.
AB  - Measurements of the concentrations of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/Fs) were made in ambient air, ash, and soil impacted by the
      open burning of wax apple and rice straw residues. Measurements showed that the
      mean PCDD/F concentration (0.458 pg I-TEQ/Nm3; international toxicity
      equivalence) in air at two wax apple orchards during open burning increased
      markedly, -8.1 times higher than that (0.057 pg I-TEQ/Nm3); before open burning.
      In addition, the mean PCDD/F concentration (0.409 pg I-TEQ/Nm3) in ambient air at
      a rice straw field was 4.6 times higher than that (0.089 pg I-TEQ/Nm3) before
      open burning. After burning the residues of wax apple stubble and rice straw, the
      contents of PCDD/F in ashes were 1.393 and 1.568 ng I-TEQ/kg-ash, respectively,
      and the contents of PCDD/F in soil were 2.258 and 2.890 ng I-TEQ/kg-soil,
      respectively. Therefore, the turnover of soil with the ash after open burning
      over years will result in the accumulation of PCDD/Fs in farm soils.

PMID- 17458465
TI  - A new alternative fuel for reduction of polycyclic aromatic hydrocarbon and
      particulate matter emissions from diesel engines.
AB  - This study investigated the emissions of polycyclic aromatic hydrocarbons (PAHs),
      carcinogenic potential of PAH and particulate matter (PM), brake-specific fuel
      consumption (BSFC), and power from diesel engines under transient cycle testing
      of six test fuels: premium diesel fuel (PDF), B100 (100% palm biodiesel), B20
      (20% palm biodiesel + 80% PDF), BP9505 (95% paraffinic fuel + 5% palm biodiesel),
      BP8020 (80% paraffinic fuel + 20% palm biodiesel), and BP100 (100% paraffinic
      fuel; Table 1). Experimental results indicated that B100, BP9505, BP8020, and
      BP100 were much safer when stored than PDF. However, we must use additives so
      that B100 and BP100 will not gel as quickly in a cold zone. Using B100, BP9505,
      and BP8020 instead of PDF reduced PM, THC, and CO emissions dramatically but
      increased CO2 slightly because of more complete combustion. The CO2-increased
      fraction of BP9505 was the lowest among test blends. Furthermore, using B100,
      B20, BP9505, and BP8020 as alternative fuels reduced total PAHs and total
      benzo[a]pyrene equivalent concentration (total BaPeq) emissions significantly.
      BP9505 had the lowest decreased fractions of power and torque and increased
      fraction of BSFC. These experimental results implied that BP9505 is feasible for
      traveling diesel vehicles. Moreover, paraffinic fuel will likely be a new
      alternative fuel in the future. Using BP9505 instead of PDF decreased PM (22.8%),
      THC (13.4%), CO (25.3%), total PAHs (88.9%), and total BaPeq (88.1%) emissions
      significantly.

PMID- 17458466
TI  - Fugitive coke oven gas emission profile by continuous line averaged open-path
      Fourier transform infrared monitoring.
AB  - Although most coke oven research is focused on the emission of polycyclic
      aromatic hydrocarbons, well-known carcinogens, little has been done on the
      emission of volatile organic compounds, some of which are also thought to be
      hazardous to workers and the environment. To profile coke oven gas (COG)
      emissions, we set up an open-path Fourier transform infrared (OP-FTIR) system on
      top of a battery of coke ovens at a steel mill located in Southern Taiwan and
      monitored average emissions in a coke processing area for 16.5 hr. Nine COGs were
      identified, including ammonia, CO, methane, ethane, ethylene, acetylene,
      propylene, cyclohexane, and O-xylene. Time series plots indicated that the type
      of pollutants differed over time, suggesting that different emission sources
      (e.g., coke pushing, quench tower, etc.) were involved at different times over
      the study period. This observation was confirmed by the low cross-correlation
      coefficients of the COGs. It was also found that, with the help of meteorological
      analysis, the data collected by the OP-FTIR system could be analyzed effectively
      to characterize differences in the location of sources. Although the traditional
      single-point samplings of emissions involves sampling various sources in a coke
      processing area at several different times and is a credible profiling of
      emissions, our findings strongly suggest that they are not nearly as efficient or
      as cost-effective as the continuous line average method used in this study. This
      method would make it easier and cheaper for engineers and health risk assessors
      to identify and to control fugitive volatile organic compound emissions and to
      improve environmental health.

PMID- 17458468
TI  - Numerical investigation of the flow profiles in the electrically enhanced
      cyclone.
AB  - A numerical model for simulation of the electrohydrodynamic flow in an
      electrically enhanced cyclone is presented. A finite element approach was applied
      to solve the coupled equations for the positive corona-induced electric field.
      Three-dimensional simulations of gas flow were carried using Reynolds-Averaged
      Navier-Stokes equations including the Reynolds stress model and the
      electrohydrodynamic effect. Numerical results show that the change in the flow
      profile because of the influence of the corona-induced electric field is apparent
      when the inlet flow rate is low but is negligible at higher flow rates.

PMID- 17458467
TI  - Model for forecasting expressway fine particulate matter and carbon monoxide
      concentration: application of regression and neural network models.
AB  - The Borman Expressway is a heavily traveled 16-mi segment of the Interstate 80/94
      freeway through Northwestern Indiana. The Lake and Porter counties through which
      this expressway passes are designated as particulate matter < 2.5 microm (PM2.5)
      and ozone 8-hr standard nonattainment areas. The Purdue University air quality
      group has been collecting PM2.5, carbon monoxide (CO), wind speed, wind
      direction, pressure, and temperature data since September 1999. In this work,
      regression and neural network models were developed for forecasting hourly PM2.5
      and CO concentrations. Time series of PM2.5 and CO concentrations, traffic data,
      and meteorological parameters were used for developing the neural network and
      regression models. The models were compared using a number of statistical quality
      indicators. Both models had reasonable accuracy in predicting hourly PM2.5
      concentration with coefficient of determination -0.80, root mean square error
      (RMSE) <4 microg/m3, and index of agreement (IA) > 0.90. For CO prediction, both
      models showed moderate forecasting performance with a coefficient of
      determination -0.55, RMSE < 0.50 ppm, and IA -0.85. These models are
      computationally less cumbersome and require less number of predictors as compared
      with the deterministic models. The availability of real time PM2.5 and CO
      forecasts will help highway managers to identify air pollution episodic events
      beforehand and to determine mitigation strategies.

PMID- 17458469
TI  - Prediction of the adsorption capacity for volatile organic compounds onto
      activated carbons by the Dubinin-Radushkevich-Langmuir model.
AB  - Prediction of the adsorption capacity for volatile organic compounds (VOCs) onto
      activated carbons is elucidated in this study. The Dubinin-Radushkevich (D-R)
      equation was first used to predict the adsorption capacity of nine aromatic and
      chlorinated VOCs onto two different activated carbons. The two key parameters of
      the D-R equation were estimated simply from the properties of the VOCs using
      quantitative structure-activity relationship and from the pore size distribution
      of the adsorbent. The approach based on the D-R equation predicted well the
      adsorption capacity at high relative pressures. However, at the relative
      pressures lower than -1.5 x 10(-3), the D-R approach may significantly
      overestimate adsorption capacity. To extrapolate the approach to lower relative
      pressures, the integration of the D-R equation and the Langmuir isotherm, called
      the D-R-L model, was proposed to predict adsorption capacity over a wide range of
      relative pressures of VOCs. In this model, the Langmuir isotherm parameters were
      extracted from the predicted D-R isotherm at high relative pressures. Therefore,
      no experimental effort was needed to obtain the parameters of the D-R-L model.
      The model successfully predicted the adsorption capacity of aromatic and
      chlorinated hydrocarbons tested onto BPL and Sorbonorit B carbons over relative
      pressures ranging from 7.4 x 10(-5) to 0.03, suggesting that the model is
      applicable at the low relative pressures of VOCs often observed in many
      environmental systems. In addition, the molecular size of organic compounds may
      be an important factor affecting the adsorption capacity of activated carbons.
      For BPL carbon, an ultramicroporous adsorbent, the limiting pore volume Wo of the
      D-R equation decreased when the kinetic diameter of the adsorbate was larger than
      6 angstroms. However, for Sorbonorit B carbon, no reduction of Wo was found,
      suggesting that the Wo may be related to the pore size distribution of the
      adsorbents, as well as to their molecular size. This size exclusion effect may
      play an important role in predicting the adsorption capacity of VOCs onto
      microporous adsorbents in the D-R-L model and in the corresponding D-R equation.

PMID- 17458473
TI  - Increasing stakes and complex dynamics in the formulary process.

PMID- 17458474
TI  - Automating the pharmacy and therapeutics process: driving a safer and more cost
      effective future.

PMID- 17458475
TI  - Who says health care is a right?

PMID- 17458476
TI  - Alzheimer's disease: overview of research and clinical advances.
AB  - Since its discovery in the early 1900's, Alzheimer's disease has continued to
      challenge the medical community. In this article, Dr. Libow presents an overview
      of the condition, and discusses such topics as prevalence, unmet needs in
      clinical research, possible causes, behavioral manifestations, and alternative
      treatments.

PMID- 17458477
TI  - A conversation with Gary Small, MD.
AB  - Alzheimer's disease research has witnessed dramatic changes over the past few
      decades. Gary Small, MD, Professor of Psychiatry and Biobehavioral Sciences and
      Parlow-Solomon Professor on Aging at the David Geffen School of Medicine,
      University of California at Los Angeles, talked to MANAGED CARE INTERFACE about
      the changes he has seen during his 25 years as an Alzheimer's disease researcher,
      and the promising developments the future holds for treatment and possible
      prevention of the disease.

PMID- 17458478
TI  - Alzheimer's disease and managed care: a convincing case for action.
AB  - More than 4 million Americans have Alzheimer's disease (AD), and practitioners
      diagnose at least 400,000 news cases eachyear. Although the disease accounts for
      $24.6 billion in direct costs annually, it also generaites an additional $36.5
      billion in indirect costs, including those attributed to lost productivityand
      absenteeism of caregivers for persons with AD. The increasing prevalence of AD
      will affect health plans with Medicare Advantage plans, as well as Medicare
      itself. Managed care faces challenges, both now and in the future, to deal with
      the effects of the disease.

PMID- 17458479
TI  - Is managed care closing substance abuse treatment units?
AB  - Despite high levels of unmet need for outpatient substance abuse treatment, a
      significant percentage of outpatient units have closed over the past several
      years. This study drew on 1999-2000 and 2005 national surveys to determine if
      managed care was associated with outpatient substance abuse treatment units'
      likelihood of surviving. Each substance abuse unit director was asked about the
      presence of any managed care contracts, percentage revenues from managed care,
      percentage of clients for whom prior authorization was required, and percentage
      of clients for whom concurrent review was required. A multiple logistic
      regression revealed that none of these factors was associated with substance
      abuse treatment unit survival. At this point, neither the presence nor the
      structure of managed care appears to affect the survival of outpatient substance
      abuse treatment units. Given the need for these facilities, however, and their
      vulnerability to closure, continued attention to managed care's potential
      influence is warranted.

PMID- 17458480
TI  - Adoption of a new technology in a Veterans Affairs national formulary system with
      local implementation: the insulin glargine example.
AB  - A study group gathered by the Pharmacy & Therapeutics Society reviewed data on
      the Department of Veterans Affairs (VA) health care system's implementation of a
      new technology (insulin glargine) for patients with diabetes. It examined local
      implementation of VA criteria for nonformulary use of insulin glargine in 21 VA
      treatment facilities that were surveyed about the issue. The examination found
      differences in the use of insulin glargine across the 21 treatment facilities and
      in the approach to implementing the criteria for nonformulary use of insulin
      glargine used at the individual VA treatment facility level. Differences were
      identified regarding the respective roles of endocrinologists and PCPs in
      prescribing insulins, including insulin glargine. The study group urges further
      short- and long-term research to better understand the utilization, cost, and
      health outcome implications of the implementation process for the nonformulary
      criteria. Lessons learned from such research could benefit other health care
      systems and formulary committees.

PMID- 17458481
TI  - Use of the levonorgestrel-IUD in the treatment of menorrhagia: improving patient
      outcomes while reducing the need for surgical management.
AB  - Menorrhagia impairs the quality of life and often leads to hysterectomy. Although
      hysterectomy provides definitive management of menorrhagia, the procedure is
      associated with morbidity, permanent sterility, and high cost. Alternative
      treatments, including pharmaceuticals, intrauterine devices, and other minor
      surgical procedures are less invasive and less expensive. In particular, the
      levonorgestrel-releasing intrauterine system (LNG-IUS), a nonsurgical, reversible
      treatment, provides effective management for many women with menorrhagia while
      minimizing morbidity and health care costs.

PMID- 17458482
TI  - Computerization in pharmacy offers opportunities for success.

PMID- 17458483
TI  - The effect of computerized physician-order entry on outpatient prescription
      errors.
AB  - Little information is available regarding the use of computerized physician-order
      entry (CPOE) in the outpatient setting or the role of pharmacists in preventing
      prescription errors with CPOE. This study evaluated the effect of CPOE on
      pharmacist-intercepted prescription errors in the outpatient setting by using
      data collected from a retrospective survey of 4527 prescriptions ordered in the
      outpatient clinics of a tertiary academic center between 1996 and 2002. The use
      of CPOE increased from 1% in 1996 to 59% in 2002 (P < .001); during the same
      period, intercepted prescription errors with computerized prescriptions decreased
      when compared with handwritten prescriptions (4.9% vs. 7.4%; P = .0048). The most
      common intercepted prescription error involved the dosage form, followed by
      quantity dispensed, medication dosage, and drug allergy. These conclusions
      suggest a decrease in outpatient intercepted prescription errors associated with
      CPOE. The pharmacist plays a critical role in the prevention of prescription
      errors, as the errors discovered in the study would have reached the patients if
      not for their interception by these health care professionals.

PMID- 17458484
TI  - Principles for developing effective disease-state management programs.

PMID- 17458485
TI  - [Bioluminescence: the potential of a molecular non-invasive biooptical imaging
      technique and improvement of animal research].
AB  - Bioluminescence is an optical imaging technique that exploits the emission of
      photons at specific wavelengths based on energy-dependent reactions catalysed by
      luciferases. The technique makes it possible to monitor measure, and track
      biological processes in living animals. A short review is presented of the
      potential of in vivo bioluminescence imaging (BLI) as a new bio-optical imaging
      technique for use in research into cancer infectious diseases, pharmacology, and
      toxicology. Bioluminescence has greatly improved the quality of longitudinal data
      obtained from animal research and has led to a significant reduction in the
      number of animals needed.

PMID- 17458486
TI  - [Mammary health: vitamin E].

PMID- 17458487
TI  - [Guess who has the cat?].

PMID- 17458488
TI  - [KNMvD's point of view about access to pasture and animal housing of dairy cows
      in the Netherlands].

PMID- 17458489
TI  - [Instruments, books and other objects memorable to (almost) forgotten opinions,
      therapies, buildings, et cetera. Mobile adjustable bed for intra-uterine
      insemination and embryo transfer in sheep and goats].

PMID- 17458490
TI  - [Satisfaction research becomes easy].

PMID- 17458491
TI  - [The advantage of cost price determination].

PMID- 17458492
TI  - [Voorjaarsdagen 2007].

PMID- 17458493
TI  - [Oncology 2007: tumors on the limbs of dogs and cats].

PMID- 17458494
TI  - From poison to remedy: the chequered history of botulinum toxin.
AB  - Botulinum toxin poisoning has afflicted mankind through the mists of time.
      However, the first incident of food-borne botulism was documented as late as the
      18th century, when the consumption of meat and blood sausages gave rise to many
      deaths throughout the kingdom of Wurttemberg in South Western Germany. The
      district medical officer Justinus Kerner (1786--1862), who was also a well-known
      German poet, published the first accurate and complete descriptions of the
      symptoms of food-borne botulism between 1817 and 1822 and attributed the
      intoxication to a biological poison. Kerner also postulated that the toxin might
      be used for treatment purposes. In 1895, an outbreak of botulism in the small
      Belgian village of Ellezelles led to the discovery of the pathogen "Clostridium
      botulinum" by Emile Pierre van Ermengem. Modern botulinum toxin treatment was
      pioneered by Alan B. Scott and Edward J. Schantz in the early 1970s, when the
      type-A serotype was used in medicine to correct strabismus. Other preparations of
      the type-A toxin were developed and manufactured in the United Kingdom, Germany,
      and China, whereas a therapeutic type-B toxin was prepared in the United States.
      To date, the toxin has been used to treat a wide variety of conditions associated
      with muscular hyperactivity, glandular hypersecretions and pain.

PMID- 17458495
TI  - Interleukin-1 alpha polymorphism has influence on late-onset sporadic Parkinson's
      disease in Taiwan.
AB  - Inflammatory events may contribute to the pathogenesis of Parkinson's disease
      (PD) and interleukin 1 (IL-1) may exert both neurotoxic and neuroprotective
      effects. We conducted a case-control study in a cohort of 493 PD cases and 388
      ethnically matched controls to investigate the association of IL-1alpha C-889T
      and IL-1beta C-511T polymorphisms with the risk of PD. No significant difference
      in the genotype distribution of the analyzed polymorphisms was found between PD
      and controls. However, after stratification by age, individuals over 70 years of
      age carrying IL-1alpha-889 C/T genotype demonstrated a significant decrease in
      risk of developing PD (OR = 0.44; 95% CI = 0.22-0.88, p = 0.021) and the decrease
      is strengthened by IL-1beta-511 T-carrying genotype (OR = 0.28; 95% CI = 0.11
      0.71, p = 0.008). Our data suggest that IL-1alpha, acting synergistically with IL
      1beta, plays role in PD susceptibility among Taiwanese people older than 70 years
      of age.

PMID- 17458496
TI  - Presence of D1- and D2-like dopamine receptors in the rat, mouse and bovine
      multiciliated ependyma.
AB  - The multiciliated ependyma forms an epithelial-like layer that could act as a
      selective barrier between the brain parenchyma and cerebrospinal fluid. In the
      present study, tyrosine hydroxylase-containing fibres have been detected in the
      basal pole of the ependymal cells of the lateral ventricles of rat, mouse and
      calf. The use of antibodies against at least two different peptide sequences of
      each D(2), D(3), D(4) and D(5) dopamine receptor subtype has allowed their
      detection in: (i) sections of mouse, rat and bovine lateral ventricles, by means
      of immunocytochemistry; and (ii) membrane protein extracts obtained from the
      ependymal layer of the bovine lateral ventricles, using immunoblotting. The
      immunocytochemical study has shown the presence of all these subtypes of dopamine
      receptors in the ependymal cells. Immunoblotting demonstrated similar
      immunoreactive bands for all receptor subtypes in both ependymal and corpus
      striatum membrane extracts.

PMID- 17458497
TI  - Differential protein expression in pancreatic islets after treatment with an
      imidazoline compound.
AB  - The effects of an imidazoline compound (BL11282) on protein expression in rat
      pancreatic islets were investigated with a proteomic approach. The compound
      increases insulin release selectively at high glucose concentrations and is
      therefore of interest in type 2 diabetes. Whole cell extracts from isolated drug
      treated and native pancreatic rat islets were compared after separation by 2-D
      gel electrophoresis. Differentially expressed proteins were identified by mass
      spectrometry; 15 proteins were selectively up-regulated and 7 selectively down
      regulated in drug-treated islets. Of special interest among the differentially
      expressed proteins are those involved in protein folding (Hsp60, protein
      disulfide isomerase, calreticulin), Ca(2+) binding (calgizzarin, calcyclin and
      annexin I) and metabolism or signalling (pyruvate kinase, alpha enolase and
      protein kinase C inhibitor 1).

PMID- 17458498
TI  - Molecular mechanisms of lymphatic vascular development.
AB  - Lymphatic vasculature has recently emerged as a prominent area in biomedical
      research because of its essential role in the maintenance of normal fluid
      homeostasis and the involvement in pathogenesis of several human diseases, such
      as solid tumor metastasis, inflammation and lymphedema. Identification of
      lymphatic endothelial specific markers and regulators, such as VEGFR-3, VEGF-C/D,
      PROX1, podoplanin, LYVE-1, ephrinB2 and FOXC2, and the development of mouse
      models have laid a foundation for our understanding of the major steps
      controlling growth and remodeling of lymphatic vessels. In this review we
      summarize recent advances in the field and discuss how this knowledge as well as
      use of model organisms, such as zebrafish and Xenopus, should allow further in
      depth analysis of the lymphatic vascular system.

PMID- 17458499
TI  - Polar transport of the plant hormone auxin - the role of PIN-FORMED (PIN)
      proteins.
AB  - The PIN-FORMED (PIN) protein family is a group of plant transmembrane proteins
      with a predicted function as secondary transporters. PINs have been shown to play
      a rate-limiting role in the catalysis of efflux of the plant growth regulator
      auxin from cells, and their asymmetrical cellular localization determines the
      direction of cell-to-cell auxin flow. There is a functional redundancy of PINs
      and their biochemical activity is regulated at many levels. PINs constitute a
      flexible network underlying the directional auxin flux (polar auxin transport)
      which provides cells in any part of the plant body with particular positional and
      temporal information. Thus, the PIN network, together with downstream auxin
      signalling system(s), coordinates plant development. This review summarizes
      recent progress in the elucidation of the role of PIN proteins in polar auxin
      transport at the cellular level, with emphasis on their structure and evolution
      and regulation of their function.

PMID- 17458500
TI  - Regulation of SNARE fusion machinery by fatty acids.
AB  - Vesicle fusion is a ubiquitous biological process involved in membrane
      trafficking and a variety of specialised events such as exocytosis and neurite
      outgrowth. The energy to drive biological membrane fusion is provided by fusion
      proteins called SNAREs. Indeed, SNARE proteins play critical roles in neuronal
      development as well as neurotransmitter and hormone release. SNARE proteins form
      a very tight alpha-helical bundle that can pull two membranes together, thereby
      initiating fusion. Whereas a great deal of attention has been paid to partner
      proteins that can affect SNARE function, recent genetic and biochemical evidence
      suggests that local lipid environment may be as important in SNARE regulation.
      Direct lipid modification of SNARE fusion proteins and their regulation by fatty
      acids following phospholipase action will be discussed here in detail. Our
      analysis highlights the fact that lipids are not a passive platform in vesicle
      fusion but intimately regulate SNARE function.

PMID- 17458501
TI  - Drugs of the future: the hormone relaxin.
AB  - The peptide hormone relaxin is emerging as a multi-functional factor in a broad
      range of target tissues including several non-reproductive organs, in addition to
      its historical role as a hormone of pregnancy. This review discusses the evidence
      that collectively demonstrates the many diverse and vital roles of relaxin: the
      homeostatic role of endogenous relaxin in mammalian pregnancy and ageing; its
      gender-related effects; the therapeutic effects of relaxin in the treatment of
      fibrosis, inflammation, cardioprotection, vasodilation and wound healing
      (angiogenesis) amongst other pathophysiological conditions, and its potential
      mechanism of action. Furthermore, translational issues using experimental models
      (to humans) and its use in various clinical trials, are described, each with
      important lessons for the design of future trials involving relaxin. The diverse
      physiological and pathological roles for relaxin have led to the search for its
      significance in humans and highlight its potential as a drug of the future.

PMID- 17458502
TI  - Epigenetic mechanisms in the context of complex diseases.
AB  - Complex diseases arise from a combination of heritable and environmental factors.
      The contribution made by environmental factors may be mediated through
      epigenetics. Epigenetics is the study of changes in gene expression that occur
      without a change in DNA sequence and are meiotically or mitotically heritable.
      Such changes in gene expression are achieved through the methylation of DNA, the
      post-translational modifications of histone proteins, and RNA-based silencing.
      Epigenetics has been implicated in complex diseases such as cancer,
      schizophrenia, bipolar disorder, autism and systemic lupus erythematosus. The
      prevalence and severity of these diseases may be influenced by factors that
      affect the epigenotype, such as ageing, folate status, in vitro fertilization and
      our ancestors' lifestyles. Although our understanding of the role played by
      epigenetics in complex diseases remains in its infancy, it has already led to the
      development of novel diagnostic methods and treatments, which augurs well for its
      future health benefits.

PMID- 17458503
TI  - Simple, mammalian cell-based assay for identification of inhibitors of the Erk
      MAP kinase pathway.
AB  - The Erk MAP kinase pathway contributes to tumor development and thus represents
      an important therapeutic target. Several inhibitors of the Erk pathway are
      presently being evaluated in clinical trials for cancer, but show limited
      efficiency thus warranting discovery of more potent inhibitors. We have developed
      a novel mammalian cell-based assay that should facilitate the identification of
      such compounds by screening molecular libraries. In rat chondrosarcoma (RCS)
      cells, treatment with fibroblast growth factor 2 (FGF2) leads to sustained
      activation of the Erk pathway, resulting in growth arrest with more than an 80%
      cell count difference between control and FGF2-treated cells after 72 h of
      treatment. The extent of both Erk activation and the growth arrest can be
      precisely modulated by the FGF2 dose. We also demonstrate that FGF2-mediated
      activation of the Erk pathway is robust and has only a limited sensitivity to the
      available MEK inhibitors. The assay is rapid, sensitive and easily adapted to
      high throughput screening. A major advantage of this system is exclusion of toxic
      compounds as false-positive hits, given the nature of the RCS response to
      inhibition of the Erk pathway, i.e. growth.

PMID- 17458504
TI  - Taurolidine: a novel anti-neoplastic agent induces apoptosis of osteosarcoma cell
      lines.
AB  - Taurolidine, the active agent of Taurolin, is a broad spectrum anti-biotic that
      has been used for over 15 years for the treatment of severe surgical infections.
      Recently, taurolidine has been shown to possess anti-neoplastic properties in
      vitro and in vivo against a variety of cancers including ovarian, colon and
      prostate. In this study we assessed the cytotoxic activity of taurolidine against
      human osteosarcoma (OS) cell lines and normal human bone cells. Treatment with
      taurolidine inhibited the growth of all ten osteosarcoma cell lines tested and
      taurolidine was equally potent against cell lines with and without distinct
      genetic defects (i.e. p53, Rb). Moreover, taurolidine-induced growth inhibition
      was found to be associated with a dose dependent increase in the number of
      apoptotic cells and apoptosis was shown to be caspase-dependent. Taurolidine
      treatment was also found to inhibit adhesion of OS cell lines. Compared to OS
      cell lines, normal bone cells in primary culture were found to be less sensitive
      to the cytotoxic and anti-adhesive effects of taurolidine. These data indicate
      that taurolidine possesses potent anti-neoplastic activity against osteosarcoma
      cell lines and may have potential as a novel OS chemotherapeutic agent.

PMID- 17458505
TI  - Phase I dose escalation and pharmacokinetic study of AZD2171, an inhibitor of the
      vascular endothelial growth factor receptor tyrosine kinase, in patients with
      hormone refractory prostate cancer (HRPC).
AB  - To explore the pharmacokinetics and tolerability of AZD2171, an inhibitor of
      vascular endothelial growth factor receptors 1 and 2, in patients with hormone
      refractory prostate cancer. Twenty-six patients received oral daily dosing of
      AZD2171 at 1, 2.5, 5, 10, 20, 30 mg. The maximum tolerated dose (MTD) was defined
      as the dose below that at which >or=33% of patients experienced a dose-limiting
      toxicity (DLT) within 21 days of initiating therapy. Pharmacokinetic analysis was
      performed. DLTs occurred at the 30 mg dose and included grade 3 events in three
      patients: fatigue (n = 3) and muscle weakness (n = 2). The pharmacokinetic
      profile revealed an effective half-life of approximately 27 h. At steady state,
      the unbound drug concentration was 4.4 times above the concentration required to
      inhibit endothelial cell proliferation in vitro. Four patients experienced PSA
      reductions within 30 days following drug discontinuation (one on 2.5 mg, two on
      20 mg and 1 on 30 mg). In two patients treated with 20 mg, post therapy PSA
      declines persisted for >17 months, despite a PSA increase on therapy. Resolution
      of adenopathy occurred in one patient persisting for >17 months. Plasma
      concentrations were maximum 2-8 h post dosing with an overall median value of 2
      h. The dose of 20 mg daily was declared as the MTD. One objective response and
      several PSA declines following the discontinuation of therapy for toxicity
      suggest that evidence of clinical efficacy may be delayed. While further study is
      indicated, careful attention must be paid to the novel toxicities of this agent
      with prolonged dosing.

PMID- 17458506
TI  - Hypoxia, gene expression, and metastasis.
AB  - Hypoxia poses many problems to the treatment of cancer. Hypoxic tumors are more
      resistant to chemotherapy and radiation. In addition, hypoxia induces a number of
      genes responsible for increased invasion, aggressiveness, and metastasis of
      tumors. The augmented metastatic potential due to hypoxia-mediated gene
      expression is discussed in this section. Particular attention is given to recent
      studies of specific genes involved in the key steps of metastasis, including
      extracellular matrix interactions, migration, and proliferation.

PMID- 17458507
TI  - Hypoxia-driven selection of the metastatic phenotype.
AB  - Intratumoral hypoxia is an independent indicator of poor patient outcome and
      increasing evidence supports a role for hypoxia in the development of metastatic
      disease. Studies suggest that the acquisition of the metastatic phenotype is not
      simply the result of dysregulated signal transduction pathways, but instead is
      achieved through a stepwise selection process driven by hypoxia. Hypoxia
      facilitates disruption of tissue integrity through repression of E-cadherin
      expression, with concomitant gain of N-cadherin expression which allows cells to
      escape anoikis. Through upregulation of urokinase-type plasminogen activator
      receptor (uPAR) expression, hypoxia enhances proteolytic activity at the invasive
      front and alters the interactions between integrins and components of the
      extracellular matrix, thereby enabling cellular invasion through the basement
      membrane and the underlying stroma. Cell motility is increased through hypoxia
      induced hepatocyte growth factor (HGF)-MET receptor signaling, resulting in cell
      migration towards the blood or lymphatic microcirculation. Hypoxia-induced
      vascular endothelial growth factor (VEGF) activity also plays a critical role in
      the dynamic tumor-stromal interactions required for the subsequent stages of
      metastasis. VEGF promotes angiogenesis and lymphangiogenesis in the primary
      tumor, providing the necessary routes for dissemination. VEGF-induced changes in
      vascular integrity and permeability promote both intravasation and extravasation,
      while VEGF-induced angiogenesis in the secondary tissue is essential for cell
      proliferation and establishment of metastatic lesions. Through regulation of
      these critical molecular targets, hypoxia promotes each step of the metastatic
      cascade and selects tumor cell populations that are able to escape the
      unfavorable microenvironment of the primary tumor.

PMID- 17458508
TI  - A systematic analysis of backbone amide assignments achieved via combinatorial
      selective labelling of amino acids.
AB  - With the advent of high-yield cell-free expressions systems, many researchers are
      exploiting selective isotope labelling of amino acids to increase the efficiency
      and accuracy of the NMR assignment process. We developed recently a combinatorial
      selective labelling (CSL) method capable of yielding large numbers of residue
      type and sequence-specific backbone amide assignments, which involves comparing
      cross-peak intensities in 1H- 15N HSQC and 2D 1H- 15N HNCO spectra collected for
      five samples containing different combinations of 13C- and 15N-labelled amino
      acids [Parker MJ, Aulton-Jones M, Hounslow A, Craven C J (2004) J Am Chem Soc
      126:5020-5021]. In this paper we develop a robust method for establishing the
      reliability of these assignments. We have performed a detailed statistical
      analysis of the CSL data collected for a model system (the B1 domain of protein G
      from Streptococcus), developing a scoring method which allows the confidence in
      assignments to be assessed, and which enables the effects of overlap on
      assignment fidelity to be predicted. To further test the scoring method and also
      to assess the performance of CSL in relation to sample quality, we have applied
      the method to the CSL data collected for GFP in our previous study.

PMID- 17458510
TI  - Aerosol characteristics and surface radiative forcing components during a dust
      outbreak in Gwangju, Republic of Korea.
AB  - Atmospheric surface aerosol radiative forcing (SARF) DeltaF, forcing efficiency
      DeltaF(e) and fractional forcing efficiency DeltaFF(e) evaluated from cloud
      screened narrowband spectral and thermal-offset-corrected radiometric
      observations during the Asia dust outbreak episodes in Gwangju, Republic of Korea
      are reported in this study. Columnar aerosol optical properties (aerosol optical
      depth (AOD), tau (alambda), Angstrom exponent alpha, mass concentration of fine
      and coarse mode particles) were also reported for the station between January
      2000 and May 2001 consisting of 211cloud-free days. Results indicate that
      majority of the AOD were within the range 0.25-0.45 while some high aerosol
      events in which AODs > or = 0.6 were observed during the severe dust episodes.
      For example, AOD increases from annual average value of 0.34 +/- 0.13 at 501 nm
      to values >0.60 during the major dust events of March 27-30 and April 7-9, 2000,
      respectively. The alpha (501-870 nm) which is often used as a qualitative
      indicator of aerosol particle size had values ranging from 0.01 to 1.77. The
      diurnal forcing efficiency DeltaDF(e) at Gwangju was estimated to be -81.10 +/-
      5.14 W m (-2)/tau (501 nm) and -47.09 +/- 2.20 W m (-2)/tau (501 nm) for the
      total solar broadband and visible band pass, respectively while the fractional
      diurnal forcing efficiency DeltaFDF(e) were -15.8 +/- 0.64%/tau (501 nm) and 
      22.87 +/- 1.13%/tau (501 nm) for the same band passes. Analyses of the 5-day air
      mass back trajectories were further developed for Gwangju in order to classify
      the air-mass and types of aerosol reaching the site during the Asia dust
      episodes.

PMID- 17458509
TI  - Maximum entropy reconstruction of joint phi, psi-distribution with a coil-library
      prior: the backbone conformation of the peptide hormone motilin in aqueous
      solution from phi and psi-dependent J-couplings.
AB  - In this paper, we present a new method for structure determination of flexible
      "random-coil" peptides. A numerical method is described, where the experimentally
      measured 3J(H(alpha)Nalpha) and [3J(H(alpha)Nalpha+1 couplings, which depend on
      the phi and psi dihedral angles, are analyzed jointly with the information from a
      coil-library through a maximum entropy approach. The coil-library is the
      distribution of dihedral angles found outside the elements of the secondary
      structure in the high-resolution protein structures. The method results in
      residue specific joint phi,psi-distribution functions, which are in agreement
      with the experimental J-couplings and minimally committal to the information in
      the coil-library. The 22-residue human peptide hormone motilin, uniformly 15N
      labeled was studied. The 3J(H(alpha)-N(i+1)) were measured from the E.COSY
      pattern in the sequential NOESY cross-peaks. By employing homodecoupling and an
      in-phase/anti-phase filter, sharp H(alpha)-resonances (about 5 Hz) were obtained
      enabling accurate determination of the coupling with minimal spectral overlap.
      Clear trends in the resulting phi,psi-distribution functions along the sequence
      are observed, with a nascent helical structure in the central part of the peptide
      and more extended conformations of the receptor binding N-terminus as the most
      prominent characteristics. From the phi,psi-distribution functions, the
      contribution from each residue to the thermodynamic entropy, i.e., the segmental
      entropies, are calculated and compared to segmental entropies estimated from 15N
      relaxation data. Remarkable agreement between the relaxation and J-couplings
      based methods is found. Residues belonging to the nascent helix and the C
      terminus show segmental entropies, of approximately -20 J K(-1) mol(-1) and -12 J
      K(-1) mol(-1), respectively, in both series. The agreement between the two
      estimates of the segmental entropy, the agreement with the observed J-couplings,
      the agreement with the CD experiments, and the assignment of population to
      sterically allowed conformations show that the phi,psi-distribution functions are
      indeed meaningful and useful descriptions of the conformational preferences for
      each residue in this flexible peptide.

PMID- 17458511
TI  - Small mammals as indicators of short-term and long-term disturbance in mixed
      prairie.
AB  - Disturbance by military maneuvers over short and long time scales may have
      differential effects on grassland communities. We assessed small mammals as
      indicators of disturbance by military maneuvers in a mixed prairie in southern
      Oklahoma USA. We examined sites on two soil series, Foard and Lawton, across a
      gradient of disturbance intensity. A MANOVA showed that abundance of small
      mammals was associated (p = 0.03) with short-term (cover of vehicle tracks)
      disturbance but was not associated (p = 0.12) with long-term (loss of soil
      organic carbon, SOC) disturbance intensity. At the individual species level,
      Sigmodon hispidus (cotton rat) and Peromyscus maniculatus (deer mouse) occurred
      across all levels of disturbance and in both soil types. Only P. maniculatus
      abundance changed (p < 0.01) with short-term disturbance and increased by about
      one individual per 5% of additional track-cover. Abundance of P. maniculatus also
      increased (p = 0.04) by about three individuals per 1% increase in soil carbon.
      Chaetodipus hispidus (hispid pocket mouse) and Reithrodontomys fulvescens
      (fulvous harvest mouse) only occurred in single soil types limiting their
      potential as more general indicators. Abundance of P. maniculatus was positively
      related to shifts in plant species composition and likely reflected changes in
      vegetation structure (i.e. litter depth) and forage availability resulting from
      disturbance. Peromyscus maniculatus may be a useful biological indicator of
      ecosystem change because it responded predictably to both long-term and short
      term disturbance and, when coupled with soil, plant, and disturbance history
      variables, can reveal land condition trends.

PMID- 17458512
TI  - Indoor and outdoor PM mass and number concentrations at schools in the Athens
      area.
AB  - Simultaneous indoor and outdoor PM10 and PM2.5 concentration measurements were
      conducted in seven primary schools in the Athens area. Both gravimetric samplers
      and continuous monitors were used. Filters were subsequently analyzed for anion
      species. Moreover ultrafine particles number concentration was monitored
      continuously indoors and outdoors. Mean 8-hr PM10 concentration was measured
      equal to 229 +/- 182 microg/m3 indoors and 166 +/- 133 microg/m3 outdoors. The
      respective PM2.5 concentrations were 82 +/- 56 microg/m3 indoors and 56 +/- 26
      microg/m3 outdoors. Ultrafine particles 8-h mean number concentration was
      measured equal to 24,000 +/- 17,900 particles/cm3 indoors and 32,000 +/- 14,200
      particles/cm3 outdoors. PM10 outdoor concentrations exhibited a greater spatial
      variability than the corresponding PM2.5 ones. I/O ratios were close or above
      1.00 for PM10 and PM2.5 and smaller than 1.00 for ultrafine particles. Very high
      I/O ratios were observed when intense activities took place. The initial results
      of the chemical analysis showed that SO4(-2) accounts for the 6.6 +/- 3.5% of the
      PM10 and NO3(1) for the 3.1 +/- 1.4%.The corresponding results for PM2.5 are 12.0
      +/- 7.7% for SO4(-2) and 3.1 +/- 1.9% for NO3-. PM2.5 SO4(-2) indoor
      concentrations were highly correlated with outdoor ones and the regression line
      had the largest slope and a very low intercept, indicative of no indoor sources
      of fine particulate SO4(-2). The results of the statistical analysis of indoor
      and outdoor concentration data support the use of SO4(-2) as a proper surrogate
      for indoor PM of outdoor origin.

PMID- 17458513
TI  - Solid waste characteristics and their relationship to gas production in tropical
      landfill.
AB  - Solid waste characteristics and landfill gas emission rate in tropical landfill
      was investigated in this study. The experiment was conducted at a pilot landfill
      cell in Thailand where fresh and two-year-old wastes in the cell were
      characterized at various depths of 1.5, 3, 4.5 and 6 m. Incoming solid wastes to
      the landfill were mainly composed of plastic and foam (24.05%). Other major
      components were food wastes (16.8%) and paper (13.3%). The determination of
      material components in disposed wastes has shown that the major identifiable
      components in the wastes were plastic and foam which are resistant to
      biodegradation. The density of solid waste increased along the depth of the
      landfill from 240 kg m(-3) at the top to 1,260 kg m(-3) at the bottom. Reduction
      of volatile solids content in waste samples along the depth of landfill suggests
      that biodegradation of solid waste has taken place to a greater extent at the
      bottom of the landfill. Gas production rates obtained from anaerobic batch
      experiment were in agreement with field measurements showing that the rates
      increased along the depth of the landfill cell. They were found in range between
      0.05 and 0.89 l kg(-1) volatile solids day(-1). Average emission rate of methane
      through the final cover soil layer was estimated as 23.95 g(-2)day(-1) and 1.17
      g(-2)day(-1) during the dry and rainy seasons, respectively.

PMID- 17458514
TI  - Thermal volatilization properties of atmospheric nanoparticles.
AB  - Thermal volatilization is explored as a means of inferring the chemical
      composition of atmospheric aerosol particles with diameters smaller than 10 nm
      (nanoparticles). Such particles contain too little mass for quantitative chemical
      determination by traditional analytical methods. Aerosols were subjected to
      increasing temperature in an oven and particle loss was measured as a function of
      temperature with the TSI model 3025 ultrafine condensation particle counter
      (UCPC), which is capable of counting particles with diameters as small as 3 nm.
      Particle nucleation was observed down stream of the oven when it was heated above
      about 400 degrees C. To reduce this artifact, the sample air down stream of the
      oven was cooled to condense the hot gases and/or the freshly nucleated particles
      before they reached the UCPC. Controlled experiments were done with pure ammonium
      sulfate (NH4)2SO4 particles. The experimental design was optimized based on the
      known concentration of pure (NH4)2SO4 particles vaporized in the oven and the
      diffusion of this material to the walls of the sampling tube before the particle
      counter.

PMID- 17458515
TI  - Favorable balance of anti-oxidant/pro-oxidant systems and ablated oxidative
      stress in Brown Norway rats in renal ischemia-reperfusion injury.
AB  - Oxidative stress is important in the pathogenesis of renal ischemia-reperfusion
      (IR) injury; however whether imbalances in reactive oxygen production and
      disposal account for susceptibility to injury is unclear. The purpose of this
      study was to compare necrosis, apoptosis, and oxidative stress in IR-resistant
      Brown Norway rats vs. IR-susceptible Sprague-Dawley (SD) rats in an in vivo model
      of renal IR injury. As superoxide (O (2) (.-) ) interacts with nitric oxide (NO)
      to form peroxynitrite, inducible NO synthase (iNOS) and nitrotyrosine were also
      examined. Renal IR was induced in SD and BN rats by bilateral clamping of renal
      arteries for 45 min followed by reperfusion for 24 h (SD 24 and BN 24,
      respectively). BN rats were resistant to renal IR injury as evidenced by lower
      plasma creatinine and decreased acute tubular necrosis. TUNEL staining analysis
      demonstrated significantly decreased apoptosis in the BN rats vs. SD rats after
      IR. Following IR, O (2) (.-) levels were also significantly lower in renal tissue
      of BN rats vs. SD rats (P < 0.05) in conjunction with a preservation of the O (2)
      (.-) dismutating protein, CuZn superoxide dismutase (CuZn SOD) (P < 0.05). This
      was accompanied by an overall decrease in 4-hydroxynonenal adducts in the BN but
      not SD rats after IR. BN rats also displayed lower iNOS expression (P < 0.05)
      resulting in lower tissue NO levels and decreased nitrotyrosine formation (P <
      0.01) following IR. Collectively these results show that the resistance of the BN
      rat to renal IR injury is associated with a favorable balance of oxidant
      production vs. oxidant removal.

PMID- 17458516
TI  - Hypoxia and antioxidants enhance soluble ICAM-1 release from cardiac fibroblasts.
AB  - Intercellular adhesion molecule-1 plays a key role in mediating inflammatory and
      immune responses. There is also increasing appreciation of the role of its
      soluble form, sICAM-1, in regulating inflammation. This study evaluated the
      effects of hypoxia and N-acetyl-L-cysteine on sICAM-1 production by adult rat
      cardiac fibroblasts. By ELISA, hypoxia was found to cause a 61% increase in sICAM
      1 in cardiac fibroblast culture supernates. However, RT-PCR did not reveal a
      concomitant increase in cell surface ICAM-1 transcript levels, suggesting that
      the increase in sICAM-1 may involve post-transcriptional and/or post
      translational mechanisms. Using pharmacological inhibitors, it was observed that
      p42/44 MAPK and PKC mediate the stimulatory effect of hypoxia on sICAM-1
      production. Remarkably, N-acetyl-L-cysteine caused a 3-fold increase in sICAM-1
      by p42/44 MAPK-, p38 MAPK- and PKC-independent mechanisms. Pyrrolidine
      dithiocarbamate, another potent antioxidant, also augmented sICAM-1. The findings
      presented in this communication underscore the link between redox status and
      sICAM-1 release from cardiac fibroblasts. Further, because hypoxia is a major
      component of myocardial ischemia and is pro-inflammatory, and both N
      acetylcysteine and pyrrolidine dithiocarbamate are clinically used antioxidants,
      the observations may have clinical significance.

PMID- 17458517
TI  - Effect of monosodium glutamate on oxidative stress and apoptosis in rat thymus.
AB  - It has been demonstrated that administration of high concentrations of monosodium
      glutamate (MSG), induce oxidative stress in different organs, but not in thymus.
      In the present study we examined the role of oxidative stress in MSG-induced
      thymocyte apoptosis. MSG was administrated intraperitoneally (4 mg/g of body
      weight) for six consecutive days. Animals were sacrificed at 1st, 7th, and 15th
      day after last MSG dose. MSG administration to animals significantly increased
      apoptotic rate of thymocytes (P < 0.01), together with significant increase of
      malondialdehyde (MDA) level (P < 0.001) and xanthine oxidase (XO) activity (P <
      0.01), in time dependent manner. Catalase activity, during examination period,
      was significantly decreased (0 < 0.01). Obtained results showed that MSG
      treatment induced oxidative stress in thymus, which may have an important role in
      thymocyte apoptosis induced by MSG.

PMID- 17458518
TI  - BRD7 suppresses the growth of Nasopharyngeal Carcinoma cells (HNE1) through
      negatively regulating beta-catenin and ERK pathways.
AB  - BRD7 is a novel gene which involved NPC in our lab. Our previous studies showed
      that BRD7 was expressed at high level in normal nasopharyngeal epithelial
      tissues, but at low level in nasopharyngeal carcinoma biopsies and cell lines. In
      these papers, we found that ectopic expression of BRD7 can decrease cell
      proliferation and capability to form colonies in soft agar. FCM (Flow cytometry)
      assay indicated that the cell cycle progression from G1 to S phase was inhibited
      and the expression of cyclinD1 was significantly decreased after being
      transfected with BRD7 in HNE1 cells (NPC cells). To further investigate the
      molecular mechanism of BRD7 suppression of NPC cells growth, the cDNA microarray
      was performed to detect difference in gene expression profile induced by BRD7.
      The results indicated that 21 genes expression were changed after being
      transfected with BRD7 and the differentially expressed gene including alpha
      catenin, cyclinD1, E2F3 was confirmed by western-blot. Next, we found that even
      though no obvious changes of the total expression of beta-catenin were observed,
      the accumulation of beta-catenin in nucleus was blocked. In addition, it was
      found that the expression of beta-catenin was up-regulated in the complex
      composed of beta-catenin and alpha-catenin in HNE1 cells induction of BRD7. So,
      we concluded that over-expression of BRD7 increased the expression of alpha
      catenin which "hold" beta-catenin in the complex and inhibited its accumulating
      in nucleus. At last, we demonstrated the c-jun, p-MEK, and p-ERK1/2 expression
      were down-regulated, and the Ap-1 promoter activity was inactive after being
      transfected with BRD7. We also found that over-expression of BRD7 can inactivate
      the c-jun and p-ERK1/2 after being treated with EGF in HNE1 cells. These results
      indicated that BRD7 played a negative role in ERK1/2 pathway. Taken together, our
      present results provide new insights for BRD7 function to inhibit NPC cells
      growth through negative regulating beta-catenin and ERK1/2 pathways.

PMID- 17458519
TI  - Assessment of organ culture for the conservation of human skin allografts.
AB  - OBJECTIVE: Human skin allografts are used in the treatment of severe burns and
      their preservation is therefore critical for optimal clinical benefit. Current
      preservation methods, such as 4 degrees C storage or cryopreservation, cannot
      prevent the decrease of tissue viability. The aim of this study was to assess
      viability and function of skin allografts in a new skin organ culture model,
      allowing conservation parameters as close as possible to physiological
      conditions: 32 degrees C, air-liquid interface and physiological skin tension.
      DESIGN: Twelve skin samples, harvested from 6 living surgical donors, were
      conserved 35 days in two conditions: conservation at 4 degrees C and organ
      culture. Viability and function of skin samples were investigated at Day 0, 7,
      14, 21, 28 and 35 using cell culture methods (trypan blue exclusion, Colony
      Forming Efficiency and Growth Rate), histopathological and histoenzymological
      studies (Ki67 immunostaining). RESULTS: In the two conditions, fibroblast and
      keratinocyte viability was progressively affected by storage, with a significant
      decrease observed after 35 days. No statistical difference could be observed
      between the two conditions. The two methods were also comparable regarding
      alterations of fibroblast and keratinocyte culture parameters, which were
      respectively significantly reduced at Day 7 and 21, compared to fresh skin. By
      contrast, histopathological and histoenzymological studies revealed a better
      preservation of skin architecture and proliferative potential at 4 degrees C, as
      compared to organ culture. CONCLUSION: These results indicate that skin organ
      culture does not provide significant advantages for skin allograft preservation.
      However, its potential use as an experimental model to study skin physiology and
      wound healing should be further evaluated.

PMID- 17458520
TI  - [Inherited tumors of the gastrointestinal tract. Diagnosis and therapeutic
      aspects].
AB  - Familial tumors of the gastrointestinal tract, which often appear as autosomal
      dominantly inherited tumor syndromes, account for only a small proportion of all
      gastrointestinal tumors. With the opportunities of modern molecular diagnostics,
      identifying the pathogenic mutation in families is often possible, with the
      option of predictive molecular testing and differentiation between mutation
      carriers and noncarriers. Thus a good chance exists for detection of early tumor
      stages by individually tailored surveillance programs and for improving prognosis
      by early intervention and prophylactic resection. Clinical manifestation,
      molecular basis at the root, individual surveillance programs, and their
      consequences for the treatment of familial gastric cancer, familial adenomatous
      polyposis coli, hereditary nonpolyposis colorectal cancer, Peutz-Jeghers
      syndrome, juvenile polyposis, hyperplastic polyposis, and familial pancreatic
      cancer are presented.

PMID- 17458521
TI  - [Breast reconstruction for patients with breast carcinoma : an analysis based on
      the data of 4,335 patients from 16 hospitals].
AB  - BACKGROUND: [corrected] The rate of breast reconstructions after mastectomy
      because of breast carcinoma has not been thoroughly studied, based on a
      representatively large data pool. METHODS: We analyzed the data of 4,335 patients
      with breast carcinoma from 16 hospitals together with the German Breast Center
      (Westdeutsches Brustcentrum). RESULTS: Of the studied patients, 34% (1,488 of
      4,335) had mastectomies. Breast reconstruction was performed in 13% (197) of
      those with mastectomy. None of the 197 with breast reconstruction was operated on
      by a plastic surgeon or had a microsurgical reconstructive procedure (free flap).
      CONCLUSION: The aim of this study is to increase the number of breast
      reconstructions after mastectomy, including microsurgical procedures, and to
      improve cooperation between gynecologists and plastic surgeons.

PMID- 17458522
TI  - [Auditory processing and perception disorders (AVWS). Three theses on diagnosis
      and therapy].

PMID- 17458523
TI  - [Hand surgery in the German DRG System 2007].
AB  - BACKGROUND: Hand surgery often needs only a short length of stay in hospital.
      Patients' comorbidity is low. Many hand surgery procedures do not need inpatient
      structures. Up until 2006 special procedures of hand surgery could not be coded.
      The DRG structure did not separate very complex and less complex operations.
      Specialized hospitals needed a proper case allocation of their patients within
      the G-DRG system. RESULTS: The DRG structure concerning hand surgery increased in
      version 2007 of the G-DRG system. The main parameter of DRG splitting is the
      complexity of the operation. Furthermore additional criteria such as more than
      one significant OR procedure, the patients' age, or special diagnoses influence
      case allocation. A special OPS code for complex cases treated with hand surgery
      was implemented. CONCLUSION: The changes in the DRG structure and the
      implementation of the new OPS code for complex cases establish a strong basis for
      the identification of different patient costs. Different case allocation leads to
      different economic impacts on departments of hand surgery. Whether the new OPS
      code becomes a DRG splitting parameter has to be calculated by the German DRG
      Institute for further DRG versions.

PMID- 17458524
TI  - [Case report: total hip replacement for osteopetrosis ossificans. Femoral neck
      nonunion].
AB  - This is a report about a young patient with marble bone disease who suffered from
      femoral neck nonunion after operative treatment of a dislocated femoral neck
      fracture. We discuss the treatment options, explain the technical procedure and
      the difficulties involved in preparations for total hip replacement with a custom
      made femoral stem, and present the early postoperative result. Furthermore we
      comment on cases reported in the literature of patients with marble bone disease
      and femoral neck fracture, femoral neck nonunion, and total hip replacement.

PMID- 17458525
TI  - An absence of aggression between non-nestmates in the bull ant Myrmecia
      nigriceps.
AB  - The ability of social insects to discriminate against non-nestmates is vital for
      maintaining colony integrity, and in most social insect species, individuals act
      aggressively towards non-nestmates that intrude into their nest. Our experimental
      field data revealed that intra-colony aggression in the primitive bulldog ant
      Myrmecia nigriceps is negligible; our series of bioassays revealed no significant
      difference in the occurrence of aggression in trials involving workers from the
      same, a close (less than 300 m) or a far (more than 1.5 km) nest. Further, non
      nestmate intruders were able to enter the nest in 60% of our trials; a similar
      level was observed in trials involving nestmates. These results suggest that
      workers of M. nigriceps are either unable to recognize alien conspecifics or that
      the costs of ignoring workers from foreign colonies are sufficiently low to favor
      low levels of inter-colony aggression in this species.

PMID- 17458526
TI  - [Depression in Parkinson's disease. Assessment and treatment].
AB  - With a prevalence of 40%, depression is the most frequent psychiatric diagnosis
      in Parkinson's disease. Quality of life in Parkinson's patients is severely
      restricted. There is still no clear evidence concerning the link between these
      disorders - findings exist that indicate common neurodegenerative processes. At
      the same time depression seems to develop as a dysfunctional coping reaction to
      the motoric, emotional, and social restrictions of Parkinson's disease. The
      authors point out particular features of the depressive symptom profile in
      patients with Parkinson's disease and recommend a step-by-step approach to
      assessing depression: screening, assessment by means of the ICD-10 criteria,
      quantitative evaluation of depressivity, and assessment of suicidality. A survey
      of current treatment options is provided: pharmacological, somatic, and
      psychological approaches are introduced and evaluated with respect to
      effectiveness in this special group of patients.

PMID- 17458527
TI  - [Twenty-five years of lithium augmentation].
AB  - Twenty-five years ago the research group of the Canadian psychiatrist de Montigny
      reported treating antidepressant-refractory depressive patients successfully by
      adding lithium to their antidepressant. The report, published in 1981 as an open
      label uncontrolled observation of only eight patients, falls short of today's
      methodological standards, but the treatment method, subsequently known as lithium
      augmentation, nonetheless was to change profoundly the pharmacological strategies
      for depressive disorders. The story of its development is remarkable, starting
      with a strictly theoretical idea conceived by Montigny and his colleagues after
      animal experiments in the 1970s had revealed that pretreatment with an
      antidepressant over several weeks led to sensitization of central nervous
      serotonin receptors. The team postulated that the proserotonergic characteristics
      of lithium, which had been systematically used as a psychotropic drug since 1949,
      could thus be used specifically to stimulate these receptors. Lithium
      augmentation demonstrated its effectiveness in the 1980s and 1990s, first in open
      label and later in randomized and placebo-controlled studies. In the late 1990s
      studies aimed at optimizing its clinical application indicated that lithium
      augmentation must be administered for at least 2 weeks, with lithium serum levels
      within the range established for prophylactic treatment and assuming patient
      response, and that the combination of lithium and antidepressant must be
      continued as a maintenance therapy for 6 to 12 months. Research has yet to
      clarify how lithium augmentation actually works. Current results show that in
      addition to the idea postulated by Montigny, lithium could also have an
      activating effect on the cortisol axis. Thanks to the sound body of evidence
      which has accrued in the meantime, lithium augmentation is recommended in most
      guidelines and treatment algorithms as a main strategy for patients who do not
      respond to antidepressant monotherapy.

PMID- 17458528
TI  - [Gene expression profiling of classic mitochondrial disorders. Its value in
      finding therapeutic strategies].
AB  - Mitochondria are semiautonomous cell organelles which possess their own genome
      (mtDNA) but nonetheless depend on the import of nuclear-encoded proteins. In
      recent years, several mutations of mtDNA have been associated with specific
      diseases of the muscles and nervous system. In 1993, the A>G point mutation at
      position 3243 of the mtDNA, until then a prominent genetic marker for
      mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
      (MELAS), was detected in patients with progressive external ophthalmoplegia
      (PEO). Due to the divergent clinical presentations of MELAS and PEO, the presence
      of potential nuclear secondary mutations or so-called modifier genes had been
      suspected. Now it is well known that a bidirectional information flow between the
      mitochondrion and the cell nucleus exists and that nuclear gene expression adapts
      to the functional status of the mitochondria. However it remains unclear when and
      how the nucleus responds to changes or mutations of the mtDNA and if there are
      indeed disease-specific biomarker genes whose expression changes in case of mtDNA
      aberrations. This review article focuses on the most recent gene expression
      profiling studies in the field of classic mitochondrial disorders.

PMID- 17458529
TI  - [Prevention of penile cancer. Value of the HPV vaccination and circumcision].
AB  - Penile cancer is rare. Penile cancers appear predominantly in non-circumcised
      men. In addition, the majority of penile cancers are associated with human
      papillomavirus infection. The present manuscript is concerned with the value of
      circumcision and HPV vaccination in the prevention of penile cancer.

PMID- 17458530
TI  - [TMPRSS2-ETS gene fusion in prostate cancer].
AB  - BACKGROUND: Recurrent chromosomal rearrangements have not been well characterized
      in common carcinomas. Using a novel bioinformatics approach, our group recently
      described a novel gene fusion in PCa. This fusion involves the androgen-regulated
      gene TMPRSS2 and so far three members of the ETS family of transcription factors
      already described as rearranged in the Ewing's family of tumors. By analogy,
      fusion status in prostate cancer may determine clinical outcome and secondary
      genetic alterations as witnessed in Ewing's tumors. MATERIAL: These novel gene
      fusions occur in the majority of prostate cancers identified by PSA screening and
      are the driving mechanism for overexpression of the three members of the ETS
      transcription factor family, either ERG (21q22.3), ETV1 (7p21.2), or ETV4
      (17q21). Considering the high incidence of prostate cancer and the high frequency
      of this gene fusion, the TMPRSS2-ETS gene fusion is the most common genetic
      aberration so far described in human malignancies. RESULTS: So far, this is the
      only gene rearrangement in any of the most prevalent cancers. As confirmed by
      other groups, we demonstrated that, within the group of ETS transcription
      factors, ERG is the most common fusion partner of the ETS genes with TMPRSS2.
      This gene fusion is considered to be an early event in PCa development. Emerging
      data suggest that gene fusion PCa demonstrates a distinct clinical course and
      thus support its use as a diagnostic test and prognostic biomarker. Also similar
      to the Philadelphia chromosome in chronic myelogenous leukemia (CML), the gene
      fusion in prostate cancer has potential as an important candidate for the
      development of targeted therapy.

PMID- 17458531
TI  - [Modern concept for treatment of the female-to-male transsexual].
AB  - BACKGROUND: The experience of our multidisciplinary team in surgical treatment of
      female-to-male trans-sexualism is presented, and our treatment concepts described
      in detail. In addition, our preferred technique of neourethra formation using a
      prefabricated free fibula flap is described. PATIENTS AND METHOD: From 1996 to
      2003, thirty-four patients underwent gender reassignment surgery as a staged
      procedure. The neourethra was constructed using an anterior vaginal flap and the
      prefabricated free fibular flap. RESULTS: There were four complete losses of the
      prefabricated fibular flap (11.7%). The neourethra stricture rate was 20.5% and
      the fistula formation rate was 14.7%. In 82.3% of the patients, the ability to
      micturate while standing was achieved. CONCLUSION: This modern concept reduces
      the complication rate and improves the quality of patient outcome.

PMID- 17458532
TI  - [Statins and probiotics in the prevention of urologic diseases].
AB  - Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, better known as
      statins, may be associated with reduced prostate cancer risk. Statins have been
      reported to demonstrate chemopreventive potentials in prostate cancer cell lines,
      but the association in observational studies has been inconclusive.Probiotics,
      defined as live microbial food supplements, have been tested for an impact on a
      variety of clinical conditions, e.g., urinary tract infections and calcium
      oxalate stone disease. Furthermore, oral administration of a lactic acid
      bacterium was effective against experimentally induced bladder tumors.
      Relationships between cancer and intake of probiotics have mainly been studied in
      bladder and colon cancer.

PMID- 17458533
TI  - [Ureteral stricture after extracorporeal shock wave lithotripsy. Case report and
      overview of the spectrum of rare side effects of modern ESWL treatment].
AB  - Extracorporeal shock wave lithotripsy (ESWL) is considered a very safe and
      noninvasive procedure for the treatment of urolithiasis. Achievements in the
      technical development of recent decades resulted in a continuous reduction of
      side effects. One of our patients, a woman with cystinuria, developed a temporary
      ureteral stricture after several sessions of ESWL. Encouraged by this observation
      we set out to explore--based on a MEDLINE literature search--published reports of
      more severe side effects observed in modern ESWL therapy. Besides hydronephrosis
      and renal colic the most common side effects were renal and perirenal hematomas
      in up to 4% in the larger series. Uncommon extrarenal complications are described
      mostly in case reports, which are also outlined in this report. The injury of
      visceral organs (liver, spleen, gut, pancreas) was published most frequently. A
      rupture or dissection of an abdominal aortic aneurysm as an outstanding serious
      complication was also reported several times. Taking obvious and well-known
      contraindications into consideration and carefully preparing the patients for the
      therapy (i.e., checking hemostasis, drug history), ESWL is a very safe procedure
      with a low risk of serious complications. Yet, postoperative clinical and
      ultrasound monitoring seems to be essential especially with respect to the
      increasing numbers of outpatient procedures.

PMID- 17458534
TI  - [Botulinum toxin A injection for treatment-refractory giggle incontinence].
AB  - A 20-year-old woman reported about giggle incontinence despite antimuscarinic
      therapy. Therefore we injected botulinum toxin A into the detrusor muscle. The
      effect of botulinum toxin A appeared about 1 week after injection and no more
      leakage was observed even during vigorous laughter. A control uroflowmetry showed
      a good voiding rate without any residual volume. Botulinum toxin A might be an
      alternative for patients with giggle incontinence after unsuccessful
      antimuscarinic treatment.

PMID- 17458535
TI  - D hordeins of Hordeum chilense: a novel source of variation for improvement of
      wheat.
AB  - The high molecular weight subunits of wheat (Triticum aestivum L.) glutenin (HMW
      GS) are important in determining the bread-making quality of flour and dough.
      There is therefore interest in transferring orthologous HMW-GS present in other
      grass species into wheat by wide crossing in order to extend the range of end use
      properties. In this work, we have isolated and characterized two genes encoding D
      hordeins from Hordeum chilense (Roem. et Schult.) lines H1 and H7, representing
      two ecotypes. The fragments were 4,305 bp for line H1 and 4,227 for line H7 and
      contained the promoter, coding and terminator regions. Both sequences differ in
      the presence of single base changes (SNPs) and insertions/deletions in the open
      reading frame (ORF). The encoded proteins comprise 870 and 896 amino acids for
      lines H1 and H7, respectively. The primary structure is similar to those of D
      hordeins of cultivated barley (H. vulgare L.) and HMW-GS from wheat. However, the
      D hordeins from H. chilense are significantly larger than those from cultivated
      barley due to the presence of longer repetitive regions. The H. chilense D
      hordeins also differ from those of cultivated barley in the distribution of the
      cysteine residues: whereas the D hordeins of cultivated barley contain ten
      cysteines with four in the repetitive domain, only nine are present in the H.
      chilense proteins with two in the repetitive domain. As in the HMW-GS, the
      central part of the D hordein proteins comprises repeated sequences based on
      short peptide motifs. The repetitive domain is divided in three regions named as
      R1 (N-terminal repeats), R2 (central degenerate repeats) and R3 (C-terminal
      repeats). Hexapeptide motifs are present throughout the repetitive domains of D
      hordeins with a consensus motif of PFQGQQ in R1 and R2 and PHQGQQ in R3. In
      addition, the tetrapeptide motif TTVS, which is characteristic of D hordeins of
      cultivated barley is present in the repetitive domain close to the protein C
      terminus.

PMID- 17458536
TI  - [Precise, computed-assisted leg angle correction with open-wedge high tibial
      osteotomy].
AB  - AIM: This prospective study investigates open-wedge high tibial osteotomy
      performed with the aid of a kinematic computer-guided navigation system. After
      the X-ray control the osteotomy was stabilized by internal LCP fixation. The aim
      of the study was to demonstrate the accuracy of the navigation system and to
      prove the reliability of the LCP fixation. METHOD: A total of 39 patients were
      operated between 2002 and 2003 following this method. The outcomes were evaluated
      at least 2 years after the surgery clinically and radiologically; 21 females (1
      female underwent bilateral osteotomy) and 18 males were included in the study
      sample. RESULTS: Prior to the osteotomy, the mean anatomic lateral tibiofemoral
      angle (aLTFA) was 181.1 degrees . The desired 4 degrees "overcorrection" of
      valgus (aLTFA 170 degrees) was found on X-rays postoperatively in all cases. The
      mean correction was 11.1 degrees. The correction achieved was stable during the 2
      year follow-up period. The osteotomy healed in all cases after 4 months. The full
      range of motion remained after the surgery in all cases. All patients were
      satisfied with their results. The Lysholm score was 55 points before and 82
      points after the osteotomy (27 points difference). CONCLUSION: The computer
      assisted open-wedge high tibial osteotomy with tricortical grafts stabilized by
      LCP fixation gives exact and reproducible results without loss of correction.

PMID- 17458537
TI  - Intensive insulin therapy in the ICU: benefit versus harm?

PMID- 17458538
TI  - Noninvasive cardiac output monitoring (NICOM): a clinical validation.
AB  - OBJECTIVE: To evaluate the clinical utility of a new device for continuous
      noninvasive cardiac output monitoring (NICOM) based on chest bio-reactance
      compared with cardiac output measured semi-continuously by thermodilution using a
      pulmonary artery catheter (PAC-CCO). DESIGN: Prospective, single-center study.
      SETTING: Intensive care unit. PATIENTS: Consecutive adult patients immediately
      after cardiac surgery. INTERVENTIONS: Cardiac output measurements obtained from
      NICOM and thermodilution were simultaneously recorded minute by minute and
      compared in 110 patients. We evaluated the accuracy, precision, responsiveness,
      and reliability of NICOM for detecting cardiac output changes. Tolerance for each
      of these parameters was specified prospectively. MEASUREMENTS AND RESULTS: A
      total of 65,888 pairs of cardiac output measurements were collected. Mean
      reference values for cardiac output ranged from 2.79 to 9.27 l/min. During
      periods of stable PAC-CCO (slope<+/-10%, 2SD/mean<20%), the correlation between
      NICOM and thermodilution was R=0.82; bias was +0.16+/-0.52 l/min (+4.0+/-11.3%),
      and relative error was 9.1%+/-7.8%. In 85% of patients the relative error was
      <20%. During periods of increasing output, slopes were similar with the two
      methods in 96% of patients and intra-class correlation was positive in 96%.
      Corresponding values during periods of decreasing output were 90% and 84%,
      respectively. Precision was always better with NICOM than with thermodilution.
      During hemodynamic challenges, changes were 3.1+/-3.8 min faster with NICOM
      (p<0.01) and amplitude of changes did not differ significantly. Finally,
      sensitivity of the NICOM for detecting significant directional changes was 93%
      and specificity was 93%. CONCLUSION: Cardiac output measured by NICOM had most
      often acceptable accuracy, precision, and responsiveness in a wide range of
      circulatory situations.

PMID- 17458539
TI  - End-inspiratory occlusion maneuver during transesophageal echocardiography for
      patent foramen ovale detection in intensive care unit patients.
AB  - OBJECTIVE: Mechanically ventilated patients in the intensive care unit cannot
      cooperate to perform the Valsalva maneuver during echocardiography for detection
      of patent foramen ovale. We evaluated the effectiveness of the end-inspiratory
      occlusion maneuver to enhance detection of patent foramen ovale in this patient
      population. DESIGN: Prospective interventional study. SETTING: The 40-bed
      intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Twenty
      five sedated and mechanically ventilated intensive care unit patients referred by
      their attending physician for bedside transesophageal echocardiography and
      agitated saline contrast study for detection of patent foramen ovale.
      INTERVENTION: Agitated saline contrast study with end-inspiratory occlusion
      maneuver. MEASUREMENTS AND RESULTS: All patients underwent a complete
      transesophageal echocardiographic study without any complications. Reduction in
      right atrial cross-sectional area (from 15.80 +/- 6.08 cm2 to 12.40 +/- 4.63 cm2;
      p < 0.001) and interatrial septum deviation during the maneuver were recorded in
      all patients. Microbubbles imaged in the left atrium within three cardiac cycles
      after injection of agitated saline diagnosed patent foramen ovale in three
      patients. When end-inspiratory occlusion maneuver was added, patent foramen ovale
      was diagnosed in seven patients (McNemar chi2 = 9.33, p = 0.0023). CONCLUSIONS:
      The end-inspiratory occlusion maneuver enhances the sensitivity of
      transesophageal echocardiography with agitated saline contrast study for
      diagnosing intermittent patent foramen ovale in critically ill mechanically
      ventilated patients.

PMID- 17458540
TI  - The effect of iNOS deletion on hepatic gluconeogenesis in hyperdynamic murine
      septic shock.
AB  - OBJECTIVE: To investigate the role of the inducible nitric oxide synthase
      activation-induced excess nitric oxide formation on the rate of hepatic glucose
      production during fully resuscitated murine septic shock. DESIGN: Prospective,
      controlled, randomized animal study. SETTING: University animal research
      laboratory. SUBJECTS: Male C57Bl/6 and B6.129P2-Nos2(tm1Lau)/J (iNOS-/-) mice.
      INTERVENTIONS: Fifteen hours after cecal ligation and puncture, anesthetized,
      mechanically ventilated and instrumented mice (wild-type controls, n = 13; iNOS-/
      , n = 12; wild-type mice receiving 5 mg.kg(-1) i.p. of the selective iNOS
      inhibitor GW274150 immediately after cecal ligation and puncture, n =8) received
      continuous i.v. hydroxyethylstarch and norepinephrine to achieve normotensive and
      hyperdynamic hemodynamics. MEASUREMENTS AND RESULTS: Measurements were recorded
      18, 21 and 24 h after cecal ligation and puncture. Liver microcirculatory
      perfusion and capillary hemoglobin O2 saturation (laser Doppler flowmetry and
      remission spectrophotometry) were well maintained in all groups. Despite
      significantly lower norepinephrine doses required to achieve the hemodynamic
      targets, the rate of hepatic glucose production (gas chromatography--mass
      spectrometry measurements of tissue isotope enrichment during continuous i.v.
      1,2,3,4,5,6-13C6-glucose infusion) at 24 h after cecal ligation and puncture was
      significantly higher in both iNOS-/- and GW274150-treated mice, which was
      concomitant with a significantly higher hepatic phosphoenolpyruvate carboxykinase
      activity (spectrophotometry) in these animals. CONCLUSIONS: In normotensive,
      hyperdynamic septic shock, both pharmacologic and genetic deletion of the
      inducible nitric oxide synthase allowed maintenance of hepatic glucose
      production, most likely due to maintained activity of the key regulatory enzyme
      of gluconeogenesis, phosphoenolpyruvate carboxykinase.

PMID- 17458541
TI  - Sleep during proportional-assist ventilation with load-adjustable gain factors in
      critically ill patients.
AB  - BACKGROUND: Proportional-assist ventilation with load-adjustable gain factors
      (PAV+) automatically adjusts the flow and volume assist to represent constant
      fractions of resistance and elastance of the respiratory system, respectively.
      Resistance and elastance are calculated at random intervals of 4-10 breaths, by
      applying a 300 ms pause maneuver at the end of selected inspirations. OBJECTIVES:
      To determine whether the large number of end-inspiratory occlusions during PAV+
      operation influences sleep quality in critically ill patients who exhibited good
      patient-ventilator synchrony during pressure support (PS, baseline). METHODS: One
      and two nights' polysomnography was performed in sedated (protocol A, n=11) and
      non-sedated (protocol B, n=9) patients, respectively, while respiratory variables
      were continuously recorded. In each protocol the patients were ventilated with
      PAV+ and PS at two levels of assist (baseline and high). RESULTS: In both
      protocols sleep quality did not differ between the modes of support or the assist
      levels. In sedated patients sleep efficiency was slightly but significantly
      higher with PAV+ than with high PS, while it did not differ between modes in non
      sedated patients. The two modes of support had comparable effects on respiratory
      variables. Independent of the mode of support and particularly at high assist, a
      significant proportion of patients developed periodic breathing during sleep (27%
      in protocol A and 44% in protocol B). CONCLUSION: In patients exhibiting good
      patient-ventilator synchrony during PS, the large number of short-term end
      inspiratory occlusions with PAV+ operation did not adversely influence sleep
      quality. With both modes high assist may cause unstable breathing during sleep.

PMID- 17458542
TI  - Different effects of a single and repeated administration of clozapine on
      phencyclidine-induced hyperlocomotion and glutamate releases in the rat medial
      prefrontal cortex at short- and long-term withdrawal from this antipsychotic.
AB  - Clozapine is a prototype of atypical antipsychotics that has a profile not only
      to block D(2)/5-HT(2A) receptors but also to enhance N-methyl-D-aspartate (NMDA)
      receptor-mediated glutamatergic neurotransmission. This study hypothesized
      different effects between a single and repeated administration of clozapine on
      NMDA receptor-mediated neurotransmission, and examined effects of these
      treatments of clozapine on a non-competitive NMDA receptor antagonist,
      phencyclidine (PCP)-induced hyperlocomotion and acute increases in glutamate
      levels in the medial prefrontal cortex (mPFC), after short- and long-term
      withdrawal from this antipsychotic. Locomotor activity and extracellular levels
      of glutamate were measured by an infrared sensor and in vivo microdialysis
      respectively. A single administration of clozapine attenuated PCP-induced
      hyperlocomotion and blocked PCP-induced increases in glutamate levels in the mPFC
      at 48 hours, but not 11 days after the injection of clozapine. Repeated
      administration of clozapine attenuated PCP-induced hyperlocomotion not only at 48
      hours, but also 11 days after the last injection of clozapine, with blocking PCP
      induced increases in glutamate levels in the mPFC. Both a single and repeated
      administration of clozapine had no effect on methamphetamine (METH)-induced
      hyperlocomotion at 48 hours or 11 days after the treatment of clozapine.
      Considering fast dissociation of clozapine from dopamine D(2) receptors and no
      effect of a single or repeated administration of clozapine on METH-induced
      hyperlocomotion, the attenuated PCP-induced hyperlocomotion by a single and
      repeated clozapine treatments cannot be explained by clozapine occupancy of
      dopamine D(2) receptors. Repeated but not a single administration of clozapine
      inhibited a 5-HT(2A/2C) agonist, DOI-induced increases in the mPFC 11 days after
      the last injection of clozapine. These findings suggest that subchronically
      treated clozapine-induced long-lasting downregulation of 5-HT(2A) receptors may
      block the enhanced PCP-induced neurochemical and behavioral changes.

PMID- 17458543
TI  - Neurotoxic effects of chronic restraint stress in the striatum of methamphetamine
      exposed rats.
AB  - RATIONALE: Stress is a common experience in drug abusers. Methamphetamine (METH)
      is an abused psychostimulant that damages dopamine and serotonin terminals
      through pro-oxidant mechanisms and glutamate-mediated excitotoxicity. Both METH
      and stress increase dopamine and glutamate release in the striatum. Since
      dopamine inhibits striatal glutamate release and METH depletes dopamine, stress
      induced glutamate release may be disinhibited after METH exposure. OBJECTIVE: We
      examined if repeated stress would worsen excitotoxic damage to the striatum after
      METH pretreatment. MATERIALS AND METHODS: In vivo microdialysis was used to
      examine stress-induced striatal glutamate release in rats pre-exposed to METH
      (7.5 mg/kg x 4 injections) or saline. The effects on striatal DA, serotonin, DAT,
      SERT, and spectrin proteolysis produced by chronic restraint stress (CRS, 6 h/day
      for 21 days) in the presence or absence of corticosterone synthesis inhibition by
      metyrapone (50 mg/kg) beginning 7 days after METH were also examined. RESULTS:
      Stress-induced glutamate release was augmented in rats pre-exposed to METH. CRS 7
      days after METH enhanced METH-induced DAT depletions from 23 to 44% in the
      nonstressed versus stressed rats, respectively. Striatal SERT and serotonin
      tissue content were decreased by 51 and 36%, respectively, in rats exposed to
      both METH and CRS but was unchanged by either treatment alone. Spectrin
      proteolysis was increased by 53% in rats treated with both METH and CRS but was
      unaffected by either treatment alone. Metyrapone blocked the effects of CRS on
      METH-induced depletions of SERT but not DAT. CONCLUSIONS: Exposure to chronic
      stress depleted striatal dopamine and serotonin terminal markers possibly through
      excitotoxic mechanisms in METH-treated rats.

PMID- 17458544
TI  - Psychiatric safety of ketamine in psychopharmacology research.
AB  - RATIONALE: A growing number of investigators are studying ketamine effects in
      healthy human subjects, but concerns remain about its safety as a research tool.
      Therefore, it is timely to revisit the safety of subanesthetic doses of ketamine
      in experimental psychopharmacology studies. OBJECTIVE: To report on the safety of
      laboratory studies with subanesthetic doses of ketamine in healthy humans using
      an existing dataset. MATERIALS AND METHODS: Medically healthy subjects with no
      personal or familial Axis I psychotic spectrum disorders were administered
      subanesthetic doses of ketamine by intravenous infusion in a series of clinical
      investigations from 1989 to 2005. The safety of ketamine administration was
      monitored in these subjects. RESULTS: Four hundred and fifty subjects received at
      least one dose of active ketamine. Eight hundred and thirty three active ketamine
      and 621 placebo infusions were administered. Ten adverse mental status events
      were documented in nine subjects/infusions that were deemed related to ketamine
      administration (2% of subjects, 1.45% of infusions). All but one adverse reaction
      resolved by the end of the test session. The side effects in the remaining
      individual were no longer clinically significant within 4 days of the test
      session. No residual sequelae were observed. CONCLUSION: Ketamine administration
      at subanesthetic doses appears to present an acceptable level of risk for
      carefully screened populations of healthy human subjects in the context of
      clinical research programs that intensively monitor subjects throughout their
      study participation.

PMID- 17458546
TI  - Base sequence- and T m-dependent DNA oligomer separation by open tubular
      capillary columns carrying complementary DNA oligomers as probes.
AB  - DNA chips prepared on a flat glass surface have unavoidable drawbacks when used
      for quantitative analysis. In an attempt to overcome this problem, we constructed
      an HPLC-type system suitable for quantitative analysis that enables base sequence
      and T (m)-dependent DNA oligomer separation in a flow system. A small open
      tubular capillary column (300-mm x 100-microm I.D.) was used. The DNA oligomers
      used as probes had an amino group at the 5'-end and were immobilized on the inner
      silica surface of the capillary column which had been sequentially treated with 3
      aminopropyltriethoxysilane, butyltrimethoxysilane, and disuccinimidylglutarate.
      Using the combination of probe-immobilized column placed in a column oven
      equipped with temperature gradient function, a nano-flow-controllable pump, a
      small sample-loading injector, and a capillary-fitted UV detector, we succeeded
      in separating complementary and non-complementary DNA oligomers in specific and
      quantitative modes. We also designed a temperature gradient strategy for
      efficient separation of target DNA oligomers in DNA mixture samples. Using a
      column carrying two different probes with similar T (m) values, their
      complementary target DNA oligomers were also separated and detected. The
      developed DNA open tubular capillary column system investigated in the present
      study could be further improved as an alternative tool to DNA chips to be used
      for the quantitative analysis of DNA or mRNA samples.

PMID- 17458547
TI  - Functional analysis of genes involved in the biosynthesis of isoprene in Bacillus
      subtilis.
AB  - In comparison to other bacteria Bacillus subtilis emits the volatile compound
      isoprene in high concentrations. Isoprene is the smallest representative of the
      natural product group of terpenoids. A search in the genome of B. subtilis
      resulted in a set of genes with yet unknown function, but putatively involved in
      the methylerythritol phosphate (MEP) pathway to isoprene. Further identification
      of these genes would give the possibility to engineer B. subtilis as a host cell
      for the production of terpenoids like the valuable plant-produced drugs
      artemisinin and paclitaxel. Conditional knock-out strains of putative genes were
      analyzed for the amount of isoprene emitted. Differences in isoprene emission
      were used to identify the function of the enzymes and of the corresponding
      selected genes in the MEP pathway. We give proof on a biochemical level that
      several of these selected genes from this species are involved in isoprene
      biosynthesis. This opens the possibilities to investigate the physiological
      function of isoprene emission and to increase the endogenous flux to the
      terpenoid precursors, isopentenyl diphosphate and dimethylallyl diphosphate, for
      the heterologous production of more complex terpenoids in B. subtilis.

PMID- 17458548
TI  - Functional identification of the gene bace16 from nematophagous bacterium
      Bacillus nematocida.
AB  - Bacillus nematocida is a Gram-positive bacterium capable of killing nematodes.
      Our recent studies identified an extracellular serine protease Bace16 in B.
      nematocida as a candidate of pathogenic factor in the infection against
      nematodes, which displayed a high similarity with the serine protease family
      subtilisin BPN', and the MEROPS ID is S08.034. To further confirm the roles that
      bace16 played in the mechanism of nematocidal pathogenesis, recombinant mature
      Bace16 (rm-Bace16) was expressed in Escherichia coli strain BL21 using pET-30
      vector system. Bioassay experiments demonstrated that the purified recombinant
      protease had the ability to degrade nematode cuticles and kill nematodes. In
      addition, a bace16 knockout mutant of B. nematocida constructed by homologous
      recombination showed considerably lower proteolytic activity and less than 50%
      nematocidal activity than the wild-type strain. These results confirmed that
      Bace16 could serve as an important virulence factor during the infectious
      process.

PMID- 17458549
TI  - Overexpression of SBPase enhances photosynthesis against high temperature stress
      in transgenic rice plants.
AB  - Activity of the Calvin cycle enzyme sedoheptulose-1,7-bisphosphatase (SBPase) was
      increased by overexpression of a rice plants 9,311 (Oryza sativa L.) cDNA in rice
      plants zhonghua11 (Oryza sativa L.). The genetic engineering enabled the plants
      to accumulate SBPase in chloroplasts and resulted in enhanced tolerance to high
      temperature stress during growth of young seedlings. Moreover, CO(2) assimilation
      of transgenic plants was significantly more tolerant to high temperature than
      that of wild-type plants. The analyses of chlorophyll fluorescence and the
      content and activation of SBPase indicated that the enhancement of photosynthesis
      to high temperature was not related to the function of photosystem II but to the
      content and activation of SBPase. Western blotting analyses showed that high
      temperature stress led to the association of SBPase with the thylakoid membranes
      from the stroma fractions. However, such an association was much more pronounced
      in wild-type plants than that in transgenic plants. The results in this study
      suggested that under high temperature stress, SBPase maintained the activation of
      ribulose-1,5-bisphosphate carboxylase-oxygenase (Rubisco) by preventing the
      sequestration of Rubisco activase to the thylakoid membranes from the soluble
      stroma fraction and thus enhanced the tolerance of CO(2) assimilation to high
      temperature stress. The results suggested that overexpression of SBPase might be
      an effective method for enhancing high temperature tolerance of plants.

PMID- 17458550
TI  - Nephrogenic systemic fibrosis is not exclusively associated with gadodiamide.

PMID- 17458551
TI  - Multimodality treatment of peritoneal carcinomatosis from colorectal cancer:
      first results of a new German centre for peritoneal surface malignancies.
AB  - BACKGROUND: The presence of peritoneal carcinomatosis arising from colorectal
      cancer is associated with a poor prognosis. It was the purpose of this study to
      analyze morbidity, mortality, and survival after major cytoreductive surgery and
      intraperitoneal chemotherapy. MATERIALS AND METHODS: Thirty-two patients with
      peritoneal carcinomatosis were operated between April 2004 and June 2006 with the
      aim of complete macroscopical cytoreduction. All had a primary colorectal
      carcinoma. Surgery in these patients was followed by hyperthermic intraperitoneal
      chemotherapy (HIPEC) consisting of mitomycin C and doxorubicin. Data were
      analyzed retrospectively. RESULTS: Of all patients, 16 had appendix and 16 non
      appendiceal colorectal carcinoma. A macroscopically complete cytoreduction was
      achieved in 24 patients by parietal and visceral peritonectomy procedures. All
      resections were combined with HIPEC. Overall morbidity was 34%. Most frequent
      surgical complications were intestinal obstruction (4/32), enteric fistula
      (2/32), pancreatitis (2/32), and bile leakage (2/32). One patient presented grade
      4 renal toxicity. There was no hospital mortality. The median follow-up was 12
      months. The 1-year overall survival rate is 96%. All patients after complete
      cytoreduction are still alive. CONCLUSIONS: Cytoreductive surgery combined with
      HIPEC is associated with an acceptable morbidity and low mortality. Complete
      cytoreduction may improve survival, particularly in well-selected patients having
      a low tumor volume and no extra-abdominal metastases.

PMID- 17458552
TI  - The neuropathology and clinical phenotype of FTD with progranulin mutations.
AB  - Mutations in the progranulin gene (PGRN), on chromosome 17q21, have recently been
      identified as a major cause of familial frontotemporal dementia (FTD). These
      cases have a characteristic pattern of neuropathology that is a distinct subtype
      of frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U), with
      lentiform neuronal intranuclear inclusions being a consistent feature. There is
      no abnormal accumulation of PGRN protein in the brain and immunohistochemical and
      biochemical analysis indicates that the ubiquitinated pathological protein is TDP
      43. In these families, FTD is inherited in an autosomal dominant fashion with
      high penetrance. The clinical phenotype is usually a combination of behavioural
      abnormality and language disturbance that is most often a form of primary
      progressive aphasia. Mild parkinsonism is common but motor neuron disease is
      notably rare. Marked variation in the disease course and clinical features are
      common, not only between families with different mutations, but also within
      individual families. This degree of clinical variability makes it difficult to
      predict which cases of familial FTD will turn out to have a PGRN mutation.

PMID- 17458553
TI  - Georg Kelling (1866-1945): the root of modern day minimal invasive surgery. A
      forgotten legend?
AB  - On 23 September 1901, at the 73rd meeting of the Society of German Natural
      Scientists and Physicians in Hamburg, following his lecture "On the inspection of
      the gullet and the stomach with flexible instruments", the surgeon and
      gastroenterologist Georg Kelling from Dresden performed a laparoscopy on a dog.
      He called this procedure coelioscopy. Kelling's ingenious idea to connect his
      oral insufflation device with the Fiedler trocar and the Nitze cystocope, led to
      the coelioscopy in 1901 and marked the hour of birth of laparoscopy. Until today,
      Georg Kelling has not experienced the appreciation he is entitled to. He is the
      forgotten pioneer of a method that today plays an important role in diagnostics
      and therapeutics. The present standard of endoscopy has confirmed the
      anticipations of Georg Kelling that he had hundred years ago. His name therefore
      deserves a fixed place in the history of medicine and especially in the history
      of endoscopy. Georg Kelling and his wife were killed during the heavy air raids
      on Dresden on 13 and 14 February 1945, but his vague footprints are still in the
      sands of medical history.

PMID- 17458554
TI  - Anthropometric measurements in the diagnosis of pelvic size: an analysis of
      maternal height and shoe size and computed tomography pelvimetric data.
AB  - BACKGROUND: To determine whether measurements of maternal height and shoe size
      are predictors of pelvic size, using erect lateral computerized tomography (CT)
      pelvimetry as gold standard. MATERIALS AND METHODS: Three hundred and fifty three
      obstetric patients out of a sequential population of 6112 (5.8%) had CT
      pelvimetry performed between January 1990 and December 1991 at the Department of
      Obstetrics and Gynecology, York District Hospital, United Kingdom. Multivariable
      logistic regression models were built using maternal height (n = 322), shoe size
      (314) and weight at last clinic visit (n = 318). The reference standard for
      pelvic size was CT Pelvimetry. Pelvic adequacy was defined as an anterior
      posterior diameter of the inlet of > or =11 cm and an anterior-posterior diameter
      of the outlet > or =10 cm on erect lateral CT pelvimetry. Women with values lower
      than these were regarded as having an inadequate pelvis. The diagnostic accuracy
      of the models was determined by the area under the receiver operating
      characteristic curve (AUC). RESULTS: The area under the curve (AUC) for maternal
      height (0.768) was not significantly greater than that for shoe size (0.686, p =
      0.163 for the difference in AUC's) and weight at the last clinic visit (0.655, p
      = 0.057 for the difference in the AUCs). The change in the AUC for each of the
      models (the full model with height, shoe size and weight [0.769]; model for
      height and shoe size [0.767] model for just height [0.768]) was also not
      significantly different. CONCLUSIONS: Measurements of maternal height, shoe size
      and weight at the last clinic visit are not useful for the identification of
      women with inadequate pelvis.

PMID- 17458556
TI  - Subconjunctival bevacizumab for corneal neovascularization.
AB  - OBJECTIVE: To report the efficacy of subconjunctival bevacizumab injection in
      patients with corneal neovascularization (NV). METHODS: This retrospective
      interventional case study included two eyes of two patients with corneal NV due
      to aqueous-deficient dry eye with filamentary keratitis in the first case, and
      corneal graft failure in the second case. Patients received a subconjunctival
      injection of 2.5 mg (0.1 ml) bevacizumab. Morphologic changes were investigated
      by slit-lamp biomicroscopy and corneal photography. RESULTS: Corneal NV was
      dramatically regressed a week after injection in the first case. In the second
      case, minor vessels were regressed while the major one did not. No infection or
      inflammation was observed. No relapse was seen within the follow-up of two to
      three months. CONCLUSION: Subconjunctival injection of bevacizumab may offer an
      additional strategy for the treatment of corneal NV.

PMID- 17458555
TI  - Serum-free cultivation of adult normal human choroidal melanocytes.
AB  - BACKGROUND: Cultures of normal choroidal melanocytes are useful in vitro models
      for the study of melanocyte biology. Current protocols involve the
      supplementation of culture media with serum, toxins, and phorbol esters, the
      latter being known as tumour-inducing agents. We therefore sought to establish a
      protocol to cultivate normal human choroidal melanocytes (NHCMs) without these
      supplements. METHODS: NHCMs were isolated by dispase II treatment, after
      isolation of retinal pigment epithelial (RPE) cells, and seeded in serum-free
      Melanocyte Growth Medium M2 in uncoated T25 cell culture flasks. Purity of the
      established cultures was proven by immunocytochemistry. Morphology of the
      cultured cells was evaluated throughout the entire cultivation period.
      Eventually, cells were cryopreserved in liquid nitrogen. RESULTS: The cultures
      underwent at least 11.5 +/- 4.5 doublings before they became senescent or culture
      was deliberately terminated. Mean generation time was 95.0 +/- 27.7 h. After
      cryopreservation, generation time was markedly increased, but proliferative
      capacity of the cells was not impaired. Cultured cells showed bipolar to
      dendritic morphology; sometimes flattened triangular cells were seen in the
      cultures. Cultured cells lost pigment after initial seeding but displayed
      continuous melanogenesis. All cultures stained positive for HMB45 antigen and S
      100 and negative for RPE-specific cytokeratins 8, 18. Only few cultures contained
      single cells that were weakly positive for matrix metalloproteinase (MMP)-2 or
      MMP-9. CONCLUSIONS: The cultivation protocol yields pure cultures of NHCMs that
      can successfully be maintained for several months without the use of serum,
      tumour-inducing substances, or toxins.

PMID- 17458557
TI  - Giant squid-hidden canard: the 3D geometry of the Hodgkin-Huxley model.
AB  - This work is motivated by the observation of remarkably slow firing in the
      uncoupled Hodgkin-Huxley model, depending on parameters tau( h ), tau( n ) that
      scale the rates of change of the gating variables. After reducing the model to an
      appropriate nondimensionalized form featuring one fast and two slow variables, we
      use geometric singular perturbation theory to analyze the model's dynamics under
      systematic variation of the parameters tau( h ), tau( n ), and applied current I.
      As expected, we find that for fixed (tau( h ), tau( n )), the model undergoes a
      transition from excitable, with a stable resting equilibrium state, to
      oscillatory, featuring classical relaxation oscillations, as I increases.
      Interestingly, mixed-mode oscillations (MMO's), featuring slow action potential
      generation, arise for an intermediate range of I values, if tau( h ) or tau( n )
      is sufficiently large. Our analysis explains in detail the geometric mechanisms
      underlying these results, which depend crucially on the presence of two slow
      variables, and allows for the quantitative estimation of transitional parameter
      values, in the singular limit. In particular, we show that the subthreshold
      oscillations in the observed MMO patterns arise through a generalized canard
      phenomenon. Finally, we discuss the relation of results obtained in the singular
      limit to the behavior observed away from, but near, this limit.

PMID- 17458559
TI  - Management of congenital tracheal agenesis.

PMID- 17458558
TI  - Grading invasive ductal carcinoma of the breast: advantages of using automated
      proliferation index instead of mitotic count.
AB  - Breast carcinomas are graded according to the "Nottingham modification of the
      Bloom-Richardson system" (SBR). The system is hindered, however, by lack of
      precision in assessing all three parameters including nuclear grade, mitosis, and
      tubular formation, leading to an element of subjectivity. Our objective was to
      evaluate a new grading system [the nuclear grade plus proliferation (N+P) system]
      for subjectivity, ease, and better representation of tumor biology. Its
      components are nuclear grade and automated proliferation index. Invasive ductal
      carcinomas, consisting of 137 SBR grade I, 247 grade II, and 266 grade III, were
      re-evaluated by the N+P system. The two systems were compared with each other and
      correlated with patients' overall survival, tumor size, angiolymphatic invasion,
      lymph node status, and biomarker status including estrogen receptor, progesterone
      receptor, p53, epidermal growth factor receptor, BCL-2, and Her-2. Although there
      was an agreement between the two systems with histologic and prognostic
      parameters studied, there was 37% disagreement when grading individual tumors.
      Fifty-three percent of SBR grade II tumors were "down-graded" to N+P grade I, and
      7% were "up-graded" to N+P grade III. Distinction among the different histologic
      grades for overall survival curves was better indicated by the N+P than the SBR
      system.

PMID- 17458560
TI  - Changes in red cell phosphate metabolism of preterm and fullterm infants with
      perinatal problems during their first month of life.
AB  - The effects of perinatal problems on red cell phosphate metabolism were studied
      in two groups of infants (preterms B and fullterms D) during the first month of
      life. All infants started milk feeding from day three after birth. The results
      were compared to those of healthy preterms (A) and fullterms (C), respectively.
      Comparisons were also made between the preterm and fullterm groups B and D. The
      preterms with perinatal problems (B) showed a significant delay in catching up
      with the plasma and red cell inorganic phosphate (Pi) levels of controls (A)
      throughout the first month of life (p < 0.05). In parallel, the erythrocyte 2,3
      diphosphoglycerate (2,3-DPG) concentrations of the sick preterms lagged
      significantly behind those of controls (p < 0.001); but the ATP levels were
      comparable between the two groups. The fullterms behaved slightly differently. No
      significant differences in plasma Pi (Pl Pi) and red cell 2,3-DPG were seen
      between the sick and healthy neonates during the month of study, while red cell
      Pi (RBC Pi) and ATP were found to be lower in the sick ones (p < 0.05). The
      fullterms with perinatal problems (D) had significantly higher Pl Pi (p < 0.05)
      and RBC Pi (p < 0.01) than preterms with problems (B) from the first week of life
      and continued in a similar pattern until the end of the month. Red cell 2,3-DPG
      concentrations were found to be significantly correlated with Pl Pi and RBC Pi in
      both preterm groups (p < 0.01) and in the sick fullterms (p < 0.001) during the
      time of the study. In the healthy fullterms 2,3-DPG was found to correlate only
      with red cell Pi (p < 0.05). Perinatal problems seem to affect Pi metabolism to a
      different degree in preterm and fullterm neonates in the first month of life.

PMID- 17458561
TI  - Analysing protein-protein interaction networks of human liver cancer cell lines
      with diverse metastasis potential.
AB  - PURPOSE: Human hepatocellular carcinoma (HCC) is one of the most mortal tumor. In
      a previous study, we had constructed glycoprotein expression profiles and
      glycoprotein databases of three human liver cancer cell lines with diverse
      metastasis potential. In order to discover vital glycoproteins related to
      pathogenesis and metastasis of HCC, in this study we analyzed previous data with
      bioinformatic approach. METHODS: We took previous data to draw the protein
      protein interaction (PPI) networks of liver cell lines by searching IntACT
      database and then using Pajeck software. Further more, we compared the
      differences between the three PPI networks by drawing the PPI networks of
      differential glycoproteins and by naming differential display PPI networks.
      RESULTS: Large numbers of proliferation and apoptosis-relative proteins interact
      with the differential glycoproteins, and among the differential glycoproteins
      there are many interactions. CONCLUSIONS: We conclude that neither single nor
      several proteins cause malignant proliferation of liver cells. "Molecule groups"
      concept should be introduced into diagnosis and metastasis prediction of the HCC.

PMID- 17458562
TI  - Markov-modeling for the administration of platinum analogues and paclitaxel as
      first-line chemotherapy as well as topotecan and liposomal doxorubicin as second
      line chemotherapy with epithelial ovarian carcinoma.
AB  - PURPOSE: So far there is no analysis available on the cost effectiveness of the
      paclitaxel/platinum-analogue combination versus carboplatin monotherapy with
      ovarian cancer. Up-to-now only a cost-utility analysis on ovarian carcinoma has
      been published (Ortega et al. in Gynecol Oncol 66(3):454-463, 1997), which in
      addition to the first-line chemotherapy included second-line chemotherapy with
      effectiveness and cost data in the analysis. Therefore, within the scope of our
      study the cost effectiveness of platinum analogues and paclitaxel as first-line
      chemotherapy as well as topotecan and liposomal doxorubicin as second-lie
      chemotherapy was to be determined with epithelial ovarian carcinoma. METHODS: For
      this purpose a decision-making Markov model was developed which represents the
      medical and economic consequences of the administration of paclitaxel and
      platinum derivatives in first-line chemotherapy and the administration of
      topotecan and liposomal doxorubicin in second-line chemotherapy in the treatment
      of epithelial ovarian carcinoma by means of data from the literature. Patients
      were treated either in the early (FIGO stage I-IIa) or advanced stage (FIGO stage
      IIb-IV). RESULTS: The therapeutic strategy caboplatin followed by topotecan costs
      20,123.91 euros, the therapeutic strategy carboplatin followed by liposomal
      doxorubicin 22,336.57 euros, the therapeutic strategy carboplatin/pactlitaxel
      followed by liposomal topotecan 29,820.64 euros and the therapeutic strategy
      carboplatin/paclitaxel followed by liposomal doxorubicin 31,560.47 euros from the
      time of diagnosis until death or survival within 5 years. With lives saved,
      accordingly of 2.55, 2.70, 2.60 and 2.65 years' costs amounted to 7,891 euros,
      8,270.35 euros, and 11,453.62 euros per year of life saved. CONCLUSIONS: Based on
      the threshold value of social willingness to pay 45,500 euros per year of life
      saved, the therapeutic strategy carboplatin followed by topotecan, the
      therapeutic strategy carboplatin followed by liposomal doxorubicin, the
      therapeutic strategy carboplatin/paclitaxel followed by topotcan and the
      therapeutic strategy carboplatin/paclitaxel followed by liposomal doxorubicin can
      be evaluated to be cost effective.

PMID- 17458563
TI  - Predictive factors for long-term effects of imatinib therapy in patients with
      inoperable/metastatic CD117(+) gastrointestinal stromal tumors (GISTs).
AB  - THE PURPOSE: To analyze the outcomes of treatment and factors predicting effects
      of imatinib (IM) therapy in inoperable/metastatic gastrointestinal stromal tumors
      (GIST) CD117(+) patients. MATERIALS AND METHODS: We identified 232 patients in a
      prospectively collected Clinical GIST Registry with advanced
      inoperable/metastatic GIST treated with IM 400-800 mg daily (129 males and 103
      females and median age 56 years). Median follow-up time was 26 months. RESULTS:
      The estimated 3-year progression-free survival (PFS; calculated from the date of
      the start of IM) was 54% and median PFS was 40.5 months. The following factors
      significantly and negatively influenced PFS in univariate analysis: poor baseline
      World Health Organization (WHO) performance status > or = 2 (P < 0.00001), tumor
      genotype indicating other than KIT exon 11 isoform (P = 0.005), baseline high
      neutrophils count (P < 0.00001), age <45 years at the diagnosis (P = 0.04),
      mitotic index >10/50 high-power fields (HPF) (P = 0.001), GIST histological type
      other than spindle-cell (P = 0.03), baseline low albumin level (P = 0.0005), low
      baseline hemoglobin level (P < 0.00001), and primary overtly malignant tumors
      (unresectable and/or metastatic lesions at presentation) (P = 0.05). We
      identified four factors negatively affecting PFS, statistically significant (P <
      0.05) in multivariate analysis: baseline poor WHO performance status > or = 2,
      high baseline neutrophils count (>5 x 10(9)/l), tumor genotype indicating the
      presence of non-exon 11 KIT mutant and mitotic index >10/50 HPF. CONCLUSIONS: We
      confirmed that many advanced GIST patients benefit from IM therapy for a
      prolonged time, although resistance to therapy is observed. We identified four
      independent biological factors influencing the PFS during long-term IM therapy.

PMID- 17458564
TI  - Functional characters combined with null models reveal inconsistency in
      mechanisms of species turnover in lacustrine fish communities.
AB  - Functional characters have the potential to act as indicators of species turnover
      between local communities. Null models provide a powerful statistical approach to
      test for patterns using functional character information. A combined null
      model/functional character approach provides the ability to distinguish between
      the effect of competition and environmental filtering on species turnover. We
      measured 13 functional characters relating directly to resource use for the fish
      species found in French lakes. We combined this functional character data with a
      null model approach to test whether co-occurring species overlapped more or less
      than expected at random for four primary niche axes. We used an environmentally
      constrained null model approach to determine if the same mechanisms were
      responsible for species turnover at different sections of the altitudinal
      gradient. Functional diversity indices were used to examine the variation in
      functional character diversity with altitude, as a test of the hypothesis that
      competitive intensity decreases with increasing environmental adversity. The
      unconstrained null model showed that environmental filtering was the dominant
      influence on species turnover between lakes. In the constrained null model, there
      was much less evidence for environmental filtering, emphasising the strong effect
      of altitude on turnover in functional character values between local communities.
      Different results were obtained for low-altitude and high-altitude lake subsets,
      with more evidence for the effect of environmental filtering being found in the
      high-altitude lakes. This demonstrates that different processes may influence
      species turnover throughout an environmental gradient. Functional diversity
      values showed a slight decrease with altitude, indicating that there was only
      weak evidence that competitive intensity decreased with increasing altitude.
      Variation resource availability and environmental stress probably cause the
      observed turnover in functional characters along the altitudinal gradient, though
      the effects of dispersal limitation and species introductions in high-altitude
      lakes cannot be ruled out.

PMID- 17458565
TI  - Needs of developing the skills of palliative care at the oncology ward: an audit
      of symptoms among 203 consecutive cancer patients in Finland.
AB  - BACKGROUND: To clarify the prevalence and severity of the symptoms, 203
      consecutive patients with breast, prostate and other cancers treated mainly for
      palliation were surveyed. MATERIALS AND METHODS: The series includes 116 men and
      87 women with the mean age of 65 years (range 27-86 years). The patients filled
      up the Edmonton Symptom Assessment System (ESAS) questionnaire with 11 items
      describing cancer-related symptoms in the visual analogue scale (VAS). RESULTS:
      Altogether, 98% of the patients reported at least 1 of the 10 symptoms. There was
      a significant difference in the score frequencies between the 10 symptoms (p =
      0.0001), fatigue receiving the highest frequency (50.8%) of the high scores.
      Fatigue was also the single most frequent symptom reported by 86.3% of the
      patients, followed by pain at effort (71.5%), sleeplessness (71.1%) and
      depression (59.0%). The most disturbing syndrome was pain (n = 48, 23.9%),
      followed by fatigue (n = 28, 13.9%), depression (9.5%) and dyspnoea (6.0%).
      Altogether, 75% had more than 5 symptoms and 10% reported all 10 symptoms. The
      total number of symptoms was not significantly associated with sex (p = 0.781) or
      age (p = 0.062), but it was associated with the diagnostic group; patients with
      breast cancer (n = 41) and those with prostate cancer (n = 44) reported fewer
      symptoms than the patients with other cancers (n = 116)(p = 0.023, Kruskal
      Wallis). CONCLUSIONS: Symptoms related to cancer are common among patients
      treated with palliative indication, but if not specifically surveyed, may remain
      un-detected and un-treated. ESAS as a clinical tool brings more symptoms to the
      attention of the physicians and helps in getting a comprehensive insight into the
      patient's problems.

PMID- 17458567
TI  - Fishing injury resulting in Mycobacterium fortuitum palmar abscess.

PMID- 17458568
TI  - Treatment failure in a case of extensively drug-resistant tuberculosis associated
      with selection of a GyrB mutant causing fluoroquinolone resistance.

PMID- 17458569
TI  - Reversion of resistance in relapsing infection caused by a glycopeptide
      intermediate methicillin-resistant Staphylococcus aureus isolate.

PMID- 17458570
TI  - Spontaneous pneumomediastinum in a patient with recent air travel.
AB  - Spontaneous pneumomediastinum (SPM) is a fairly uncommon condition in which free
      air is present in the mediastinum, often in young patients without injury or
      serious underlying pulmonary disease. We present a case of SPM in a 36-year-old
      man with no pertinent medical history who presented with chest pain after a 3-h
      flight. To the best of our knowledge, this is the first known case in radiology
      literature of SPM caused by increased intra-alveolar pressure secondary to
      increased altitude.

PMID- 17458571
TI  - Recoverable cognitive dysfunction in older persons.

PMID- 17458572
TI  - Case report: Disseminated intravascular coagulation as the presenting sign of
      metastatic prostate cancer.

PMID- 17458573
TI  - Predicting diagnostic accuracy.

PMID- 17458576
TI  - The effect of whole-body cryostimulation on lysosomal enzyme activity in kayakers
      during training.
AB  - Effects of whole-body cryostimulation on lysosomal enzyme activity: acid
      phosphatase (AcP), arylsulphatase (ASA) and cathepsin D (CTS D), as well as on
      the creatine kinase (CK), and the cortisol concentration in the serum of kayakers
      during training were studied. Additionally, the effect of a single
      cryostimulation treatment in untrained men was evaluated. The kayakers were
      subjected to a ten-day training cycle, in which training sessions were preceded
      by whole-body cryostimulation at a temperature ranging from -120 to -140 degrees
      C, and to a control training without cryostimulation. Blood samples were taken
      from the kayakers before the training and after the sixth and tenth day of
      training and from untrained men before and after cryostimulation. The single
      cryostimulation caused a 30% (P < 0.05) decrease in the CK activity in untrained
      men. After the sixth day of training with cryostimulation, the activity of ASA
      was 46% (P < 0.001), AcP 32% (P < 0.05) and CK 34% lower (P < 0.05) than after
      the sixth day of training without cryostimulation. The results support that
      preceding training with whole-body cryostimulation alleviates exertion stress by
      a stabilisation of lysosomal membranes.

PMID- 17458577
TI  - Angiogenesis in cancer: molecular mechanisms, clinical impact.
AB  - BACKGROUND: Angiogenesis, the formation of new blood vessels from the endothelium
      of the existing vasculature, is fundamental in tumor growth, progression, and
      metastasis. Inhibiting tumor angiogenesis is a promising strategy for treatment
      of cancer and has been successfully transferred from preclinical to clinical
      application in recent years. Whereas conventional therapeutic approaches, e.g.
      chemotherapy and radiation, are focussing on tumor cells, antiangiogenic therapy
      is directed against the tumor supplying blood vessels. MATERIALS AND METHODS:
      This review will summarize important molecular mechanisms of tumor angiogenesis
      and advances in the design of antiangiogenic drugs. Furthermore, clinical
      implications of antiangiogenic therapy in surgical oncology will be discussed.
      RESULTS: First antiangiogenic drugs have been approved for treatment of advanced
      solid tumors in several countries. Leading antiangiogenic drugs are designed to
      inhibit vascular endothelial growth factor-mediated tumor angiogenesis. Combining
      antiangiogenic agents with conventional chemotherapy or radiation is currently
      investigated clinically with great emphasis to realize a multimodal tumor
      therapy, targeting both the tumor cell and tumor vascular compartment.
      CONCLUSION: Antiangiogenic tumor therapy represents a promising strategy for
      treatment of cancer and will most likely exhibit its clinical potential in
      combination with established standard tumor therapies in the future.

PMID- 17458580
TI  - Bioconversion of municipal solid waste to glucose for bio-ethanol production.
AB  - Selected biodegradable municipal solid waste fractions were subjected to fifteen
      different pre-hydrolysis treatments to obtain the highest glucose yield for bio
      ethanol production. Pre-hydrolysis treatments consisted of dilute acid
      (H(2)SO(4), HNO(3) or HCl, 1 and 4%, 180 min, 60 degrees C), steam treatment (121
      and 134 degrees C, 15 min), microwave treatment (700 W, 2 min) or a combination
      of two of them. Enzymatic hydrolysis was carried out with Trichoderma reesei and
      Trichoderma viride (10 and 60 FPU g(-1) substrate). Glucose yields were compared
      using a factorial experimental design. The highest glucose yield (72.80%) was
      obtained with a pre-hydrolysis treatment consisting of H(2)SO(4) at 1%
      concentration, followed by steam treatment at 121 degrees C, and enzymatic
      hydrolysis with Trichoderma viride at 60 FPU g(-1) substrate. The contribution of
      enzyme loading and acid concentration was significantly higher (49.39 and 47.70%,
      respectively), than the contribution of temperature during steam treatment
      (0.13%) to the glucose yield.

PMID- 17458579
TI  - Initial support for the hypothesis that PAR2 is involved in the immune response
      to Nippostrongylus brasiliensis in mice.
AB  - Protease-activated receptor 2 (PAR(2)) is a cell surface receptor that detects
      trypsin and trypsin-like enzymes. Although the precise pathophysiological roles
      of PAR(2) are yet to be determined, the receptor has been broadly implicated in
      inflammation and allergy. However, no studies have investigated the possible
      roles of PAR(2) in hosts infected by parasitic helminths. Therefore, in this
      preliminary investigation, we compared the infectivity of the nematode
      Nippostrongylus brasiliensis in mice lacking the PAR(2) gene (PAR2-/- ) and in
      their 'background-strain' controls (129SV). PAR2-/- mice displayed elevated fecal
      egg counts and decreased levels of total serum IgE, after a subcutaneous
      infection with 900 infective third-stage N. brasiliensis larvae compared with
      129SV mice that were not susceptible to infection. In addition, in a separate
      study in BALB/c mice, two immunological hallmarks of parasite infection, IgE- and
      IL-10-expressing lymphocytes, were shown to be augmented after the
      coadministration of the classic antigen ovalbumin with the PAR(2)-activating
      peptide SLIGRL (single letter amino acid sequence) but not the inactive reverse
      peptide LRGILS. These findings provide initial support for the proposal that
      PAR(2) is a recognition receptor for nematode-derived proteases.

PMID- 17458582
TI  - Electro-mechanical stability of surface EMG sensors.
AB  - This study compared the performance of surface electromyographic (sEMG) sensors
      for different detection conditions affecting the electro-mechanical stability
      between the sensor and its contact with the skin. These comparisons were made to
      gain a better understanding of how specific characteristics of sensor design and
      use may alter the ability of sEMG sensors to detect signals with high fidelity
      under conditions of vigorous activity. The first part of the study investigated
      the effect of different detection surface contours and adhesive tapes on the
      ability of the sensor to remain in electrical contact with the skin. The second
      part of the study investigated the effects of different skin preparations and
      hydrophilic gels on the production of movement artifact resulting from sinusoidal
      and impact mechanical perturbations. Both parts of the study evaluated sensor
      performance under dry skin and wet skin (from perspiration) conditions. We found
      that contouring the detection surface and adding a more adhesive double-sided
      tape were effective in increasing the forces needed to disrupt the electrical
      contact between the electrodes and the skin for both dry skin and wet skin
      conditions. The mechanical perturbation tests demonstrated that hydrophilic gel
      applied to the detection surface of the sensor produced greater movement
      artifacts compared to sensors without gel, particularly when the sensors were
      tested under conditions in which perspiration was present on the skin. The use of
      a surfactant skin preparation did not influence the amount of movement artifacts
      that resulted from either the sinusoidal or impact perturbations. The importance
      of these findings is discussed in terms of their implications for improving sEMG
      signal fidelity through sensor design modifications and procedures for
      interfacing them with the skin.

PMID- 17458583
TI  - A survey of acute pain services in teaching hospitals in the Republic of Ireland.
AB  - BACKGROUND: Acute Pain Services (APS) evolved in response to the desire for
      improved management of postoperative pain. AIMS: To assess the status of APS in
      teaching hospitals in Ireland. This information has not previously been
      available. METHODS: Postal questionnaires were sent to all teaching hospitals in
      the Republic of Ireland (n = 40). The questionnaire dealt with current and future
      APS. RESULTS: Thirty-one out of the 40 teaching hospitals returned a completed
      questionnaire (78% response). Seventy-one per cent of respondents had formalised
      APS of which 85% were established after 1990. Ninety percent of respondents
      selected postoperative pain as their primary target. Pain was included in quality
      assurance in 73% of hospitals and 87% of clinicians believed the trend in pain
      consultations is increasing. CONCLUSIONS: Despite a growing trend in pain
      management and publication of guidelines, only 71% (22/31) of teaching hospitals
      in the Republic of Ireland have such services. Further resources are needed to
      address this deficiency.

PMID- 17458584
TI  - Temporal patterns in lung cancer death rates in Ireland.
AB  - BACKGROUND: Distinct temporal patterns can be identified through estimating
      annual-percent-changes (APC) in age-specific disease rates, but APCs in lung
      cancer rates among the youngest adults can also reflect the recent changing
      smoking habits of a population. METHOD: Lung cancer mortality rates from 1970 to
      1999 were investigated in Ireland, using the Joinpoint regression modelling
      technique. RESULTS: In the most recent decade (1989-1999) male lung cancer death
      rates showed a significant annual decline (-2.4%), but female annual rates have
      scarcely decelerated (0.1%). The combined gender youngest adults (30-39 year
      olds) showed decreasing rates, but the annual decline in the youngest female
      rates were significant only from 1970 to 1990 and thereafter increased non
      significantly. CONCLUSION: Unlike male lung cancer death rates, the overall
      female rates are increasing significantly. While the combined gender youngest
      adult rates are decreasing, the apparent reversal in trends among the youngest
      female rates from 1990 onwards is worrying.

PMID- 17458585
TI  - Biochemistry of anterior, medial, and posterior genioglossus muscle in the rat.
AB  - The tongue plays a vital role in swallowing actions. However, tongue muscles have
      been understudied, and it is unclear if tongue muscles are homogeneous with
      respect to muscle fiber-type distribution. We examined myosin heavy chain (MHC)
      composition of anterior, medial, and posterior sections of the genioglossus
      muscle (GG) using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) in ten adult (9 months old) male Fischer 344/Brown Norway hybrid rats. We
      found that Type IIx MHC predominated in the anterior, medial, and posterior
      regions of the GG muscle (p=0.002), followed by IIa, then IIb. The anterior GG
      contained a significantly greater (p=0.004) proportion of Type IIa than did the
      medial or posterior regions, while the posterior GG contained a significantly
      greater (p=0.002) proportion of Type IIb MHC than did the medial or anterior GG.
      Accordingly, we found variable expression of MHC isoforms across anterior,
      medial, and posterior portions of the GG muscle, with more fast-contracting
      isoforms found posteriorly. Because motor control of the tongue requires precise
      and rapid movements for bolus manipulation and airway protection, variable
      expression of MHC isoforms along the anteroposterior axis of the GG muscle may be
      required to efficiently achieve deglutition and maintenance of airway patency.

PMID- 17458586
TI  - Oncologic results of laparoscopic D3 lymphadenectomy for male sigmoid and upper
      rectal cancer with clinically positive lymph nodes.
AB  - BACKGROUND: Many Japanese surgeons routinely perform extended D3 lymph node
      dissection for the treatment of advanced rectosigmoid cancer with a view to
      achieving better tumor control. However, the application of a laparoscopic
      approach to perform D3 lymphadenectomy has been challenging. This phase 2
      prospective study aimed to explore the oncologic results of this surgical
      approach. METHODS: The study was conducted during a 6-year period, in
      consideration of median follow-up time being >3 years. The study subjects were
      tumor, node, metastasis system stage III rectosigmoid cancer staged by clinical
      images. The extent of D3 dissection and the postoperative lymph node mapping were
      according to the guidelines of the Japanese Society for Cancer of the Colon and
      Rectum. Patients were stratified according to the histopathologically proved
      highest level of involved lymph nodes and placed into N0, N1, N2, and N3 groups.
      The primary end points of the study were the estimated time to recurrence and 5
      year recurrence rate of cancer after laparoscopic D3 dissection. RESULTS: The
      estimated 5-year recurrence rate (20% in the N0 group [n = 10]; 25% in N1 [n =
      44]; 33.3% in N2 [n = 30]; and 42.8% in N3 [n = 14]), time to recurrence (mean
      [95% confidence interval] 59.8 [42.6-76.9] months in the N0 group; 56.8 [48.3
      65.2] months in N1; 46.8 [37.5-56.1] months in N2; and 43.9 [28.3-59.4] months in
      N3), and recurrence patterns were without significant difference (all P values
      >.05) among N0, N1, N2, and N3 groups. Therefore, by laparoscopic wide anatomic
      dissection, patients with lymph node involvement could be treated as well as
      those without lymph node metastasis. Laparoscopic D3 dissection facilitated the
      collection of more lymph nodes (mean +/- standard deviation, 27.4 +/- 4.2) for
      histopathologic examination. Mapping of dissected lymph nodes showed that 18.2%
      (16 of 88) patients had skip lymph node metastasis. D3 dissection facilitated
      upstaging of cancer (from N0 to N3) in five patients (5.1%). However, this
      procedure resulted in transient voiding dysfunction in 77.5% patients and loss of
      ejaculatory function in 91.7%. By laparoscopic approach, the D3 lymph node
      dissection was safely performed through small wounds, resulting in quick
      functional recovery and only moderate blood loss (324.8 +/- 44.5 mL), but at the
      expense of a long operation time (294.4 +/- 34.8 minutes). CONCLUSIONS: The good
      short-term oncologic results and quick convalescence mean that the laparoscopic
      D3 dissection may be recommended for patients with stage III rectosigmoid cancer
      who could accept the genitourinary dysfunction.

PMID- 17458587
TI  - Concepts and preliminary data toward the realization of image-guided liver
      surgery.
AB  - Image-guided surgery provides navigational assistance to the surgeon by
      displaying the surgical probe position on a set of preoperative tomograms in real
      time. In this study, the feasibility of implementing image-guided surgery
      concepts into liver surgery was examined during eight hepatic resection
      procedures. Preoperative tomographic image data were acquired and processed.
      Accompanying intraoperative data on liver shape and position were obtained
      through optically tracked probes and laser range scanning technology. The
      preoperative and intraoperative representations of the liver surface were aligned
      using the iterative closest point surface matching algorithm. Surface
      registrations resulted in mean residual errors from 2 to 6 mm, with errors of
      target surface regions being below a stated goal of 1 cm. Issues affecting
      registration accuracy include liver motion due to respiration, the quality of the
      intraoperative surface data, and intraoperative organ deformation. Respiratory
      motion was quantified during the procedures as cyclical, primarily along the
      cranial-caudal direction. The resulting registrations were more robust and
      accurate when using laser range scanning to rapidly acquire thousands of points
      on the liver surface and when capturing unique geometric regions on the liver
      surface, such as the inferior edge. Finally, finite element models recovered much
      of the observed intraoperative deformation, further decreasing errors in the
      registration. Image-guided liver surgery has shown the potential to provide
      surgeons with important navigation aids that could increase the accuracy of
      targeting lesions and the number of patients eligible for surgical resection.

PMID- 17458588
TI  - The pathogenesis of Barrett's esophagus: secondary bile acids upregulate
      intestinal differentiation factor CDX2 expression in esophageal cells.
AB  - INTRODUCTION: Clinical evidence strongly suggests that bile acids are important
      in the development of Barrett's esophagus, although the mechanism remains
      unknown. Caudal-related homeobox 2 (CDX2) is a transcription factor recently
      implicated in early differentiation and maintenance of normal intestinal
      epithelium and is suggested to play a key role in the pathogenesis of intestinal
      metaplasia in Barrett's esophagus. OBJECTIVE: The aim of this study was to
      investigate the effect of primary and secondary bile acids on CDX2 mRNA
      expression in human esophageal cells. METHODS: Human esophageal cells: (1)
      squamous, immortalized by SV40 (Het-1A); (2) adenocarcinoma (SEG-1); and (3)
      squamous cell carcinoma (HKESC-1 & HKESC-2), were exposed in cell culture for 1
      24 h to 100-1,000 microM deoxycholic, chenodeoxycholic, and glycocholic acids.
      Total RNA was extracted before and after bile acid treatment and reverse
      transcribed to cDNA. CDX2 mRNA expression was determined by both quantitative
      real-time and reverse transcription PCR (RT-PCR). RESULTS: CDX2 mRNA expression
      was absent before bile acid exposure in all cell lines. CDX2 expression increased
      in a dose- and time-dependent fashion with deoxycholic and chenodeoxycholic, but
      not glycocholic, acid in all four cell lines. The maximal induction of CDX2
      expression was seen in SEG-1 adenocarcinoma cells. Expression in Het-1A cells
      also increased significantly as did expression in HKESC-1,2 cells, although to a
      lesser extent than in adenocarcinoma. CONCLUSIONS: These findings show that
      secondary bile acid stimulation upregulates CDX2 gene expression in both normal
      and cancer cell lines. They further support the role of bile acids in the
      pathogenesis of Barrett's esophagus and link the clinical evidence of a high
      prevalence of luminal bile acids in Barrett's to expression of the gene thought
      to be responsible for the phenotypic expression of intestinal metaplasia.

PMID- 17458590
TI  - Viability of endoscopic and excisional treatment of early rectal carcinoids.
AB  - With the advent of endoscopy, the incidence of rectal carcinoid tumors has not
      only risen, but the majority are localized at presentation. This has led to
      excisional and/or ablative therapy in lieu of radical resections. A single
      institute's experience with rectal carcinoids was reviewed to determine the
      impact this approach has had on outcomes, and evaluate any selection criteria for
      optimizing patient survival. A single institute's tumor registry was
      retrospectively queried, identifying 14 patients with rectal carcinoid tumors
      over a 28-year period. The mean age at diagnosis was 52.1 +/- 14.4 years. Six of
      the 14 patients were female. Presenting symptoms included a change in bowel
      habits in six (38%), rectal bleeding in six (38%), and abdominal pain or
      distention in five (31%) patients. No patient had symptoms consistent with
      carcinoid syndrome. The rectal carcinoids were a mean 9.2 +/- 3.4 cm from the
      anal verge and a mean 9 +/- 6 mm in size. Endoscopic and/or transanal
      excision/fulguration techniques treated 11 (79%) patients, whereas two (14%)
      patients underwent a low anterior resection (LAR). Surveillance entailed periodic
      endoscopy for a median 65 months (range 8-281). No patient developed recurrent
      carcinoid disease for a 20-year overall survival of 70%.

PMID- 17458589
TI  - Cholecystosteatosis: an explanation for increased cholecystectomy rates.
AB  - INTRODUCTION: Over the past decade, obesity has become epidemic, and the number
      of cholecystectomies as well as the percentage with acalculous cholecystitis have
      increased. We have recently reported that congenitally obese mice and lean mice
      fed a high fat diet have increased gallbladder wall lipids and poor gallbladder
      emptying. Therefore, we tested the hypothesis that compared to patients with a
      normal gallbladder, patients with both acalculous and calculous cholecystitis
      would have increased gallbladder wall fat. METHODS: Sixteen patients who
      underwent cholecystectomy for acalculous cholecystitis were identified. Sixteen
      nondiseased controls who underwent incidental cholecystectomy during surgery for
      liver or pancreatic disease and 16 diseased controls whose gallbladder was
      removed for chronic calculous cholecystitis were chosen to match the acalculous
      patients for gender and Body Mass Index. Pathology specimens were reviewed in a
      blinded fashion for gallbladder wall fat, thickness, and inflammation. RESULTS:
      Acalculous cholecystitis patients were younger (p < 0.01) than nondiseased or
      diseased controls. Gallbladder wall fat was significantly increased (p < 0.02) in
      the acalculous and calculous cholecystitis patients compared to the nondiseased
      controls. Gallbladder wall thickness (p < 0.02) and inflammatory score (p < 0.01)
      were highest in the calculous cholecystitis patients. CONCLUSIONS: These data
      suggest that compared to nondiseased controls, (1) patients with acalculous
      cholecystitis are younger and have increased gallbladder fat and (2) patients
      with calculous cholecystitis have increased gallbladder fat and inflammation. We
      conclude that increased gallbladder fat may lead to poor gallbladder emptying and
      biliary symptoms. Thus, cholecystosteatosis may explain, in part, the increased
      need for cholecystectomy and the higher percentage of these patients with
      acalculous cholecystitis.

PMID- 17458591
TI  - Mild acute biliary pancreatitis vs cholelithiasis: are there differences in the
      rate of choledocholithiasis?
AB  - The rate of choledocholithiasis at the time of elective surgery after mild acute
      biliary pancreatitis is still unclear because it decreases rapidly after the
      onset. The aims of this study are as follows: (1) To investigate whether the
      incidence of choledocholithiasis in mild biliary pancreatitis is higher than in
      patients with symptomatic cholelithiasis. (2) To evaluate the usefulness of
      intraoperative cholangiography in the diagnosis of unsuspected
      choledocholithiasis in mild pancreatitis. Prospective study including 130
      patients undergoing laparoscopic surgery and classified into two groups: mild
      biliary pancreatitis (n = 44) and symptomatic cholelithiasis (n = 86).
      Choledocholithiasis was evaluated by endoscopic cholangiopancreatography,
      magnetic resonance, and intraoperative cholangiography. Preoperatively,
      choledocholithiasis was identified in five patients with symptomatic
      cholelithiasis and two with biliary pancreatitis (5.81 vs 4.54%; p = 0.472). In
      117 cases (90%), intraoperative cholangiography was successfully performed,
      identifying unsuspected choledocholithiasis in five patients of the colelithiasis
      group and in three in the group of pancreatitis (5.81 vs 6.81%; p = 0.492). The
      total number of patients with choledocholithiasis in the whole series was 15
      (11.5%); 11.6% in colelithiasis group vs 11.4% in biliary pancreatitis group; p =
      0.605. The rate of choledocholithiasis was not significantly different between
      the groups of patients with mild acute biliary pancreatitis and symptomatic
      cholelithiasis. Intraoperative cholangiography identified unsuspected
      choledocholithiasis in 6.81% of patients with mild acute biliary pancreatitis.

PMID- 17458592
TI  - Clinicopathologic and immunohistochemistry characterization of synchronous
      multiple primary gastric adenocarcinoma.
AB  - The aim of this investigation was to evaluate clinicopathologic and
      immunohistochemical characteristics of synchronous primary gastric
      adenocarcinomas. Immunohistochemistry for p53 (suppressor pathway) and for hMLH1,
      hMSH2, and hMSH6 (mutator pathway) was performed using ABC-technique
      amplification by biotinylated tyramide. Synchronous primary gastric
      adenocarcinomas were detected in 19/553 (3.43%) of the patients. The tumors were
      localized in distal stomach in 22, body in 14, and proximal in five. There was a
      predominance of intestinal type in the group of synchronic tumors compared to the
      solitary lesions, 73.2 vs 37.3%, p = 0.001. Synchronous neoplasias were diagnosed
      in earlier stage than solitary neoplasias, T1-T2 = 60.9% vs T1-T2 = 28.4%, p =
      0.0001; and N0 = 68.4% vs N0 = 26.2%, p = 0.001. p53 was detected in 52.6% of the
      patients with synchronous tumors. Altered hMLH1 immunoexpression occurred in
      26.3% of the patients and hMSH6 in 5.3%. hMSH2 immunoreactivity was positive in
      all tumors. p53 was solely detected in 17 tumors, while hMLH1 was altered in
      10/24 negative p53 tumors, p = 0.01. Synchronous gastric adenocarcinomas
      presented higher frequency of intestinal type and early gastric cancer in
      comparison to solitary gastric cancer. Two routes of carcinogenesis, mutator, and
      suppressor appear to be involved independently in the development of synchronous
      tumors.

PMID- 17458593
TI  - Effectiveness of diagnostic paracentesis and ascites analysis for suspected
      strangulation obstruction.
AB  - Strangulation obstruction is a surgical emergency, but its accurate diagnosis and
      timely surgical treatment are still matters of debate. We conducted a prospective
      observational study. We performed diagnostic paracentesis preoperatively for
      patients with suspected strangulation obstruction or, if that was impossible, we
      obtained ascites at the time of laparotomy. We examined each specimen to see
      whether ascites color and laboratory parameters could be reliable indicators of
      strangulation obstruction. During 18 months, 32 patients had suspected
      strangulation obstruction. At laparotomy, we confirmed strangulation obstruction
      in 21 patients, simple obstruction in two patients, and pseudo-obstruction in one
      patient. We treated eight patients conservatively, including one patient with a
      complication. We identified ascites red blood cell count, hematocrit, and lactic
      acid as indicators for strangulation obstruction by univariate analysis. An
      ascites red blood cell count was statistically high in cases with strangulation
      obstruction by multivariate analysis. Ascites red blood cell count above
      20,000/mm(3) had a positive predictive value for strangulation obstruction of
      100%, and above 40,000/mm(3), bowel resection was highly necessary. Diagnostic
      paracentesis and ascites analysis are useful methods for diagnosis of
      strangulation obstruction. Diagnostic paracentesis and ascites analysis should be
      combined with careful clinical exams for diagnosis of strangulation obstruction.

PMID- 17458594
TI  - The effect of L-arginine and aprotinin on intestinal ischemia-reperfusion injury.
AB  - BACKGROUND: Intestinal ischemia/reperfusion (I/R) results in local mucosal
      injury, systemic injuries, and organ dysfunction. These injuries are
      characterized by altered microvascular and epithelial permeability and villous
      damage. Activation of neutrophils, platelets, and endothelial factors are known
      to be involved in this process. Cytokines such as TNF-alpha, IL-1, IL-6, and
      oxygen-derived free radicals are believed to be important pathogenic mediators.
      Capillary no-reflow is also known to play a role in I/R. The aim of our study was
      to examine the role of L-arginine, a known nitric oxide (NO) donor, and
      aprotinin, a protease inhibitor with multiple effects, on intestinal I/R.
      METHODS: Pigs weighing 20-25 kg were used. Ischemia was established by clamping
      the superior mesenteric artery (SMA) at its origin and was sustained for 2 hours.
      Duration of reperfusion was 2 hours. The animals were divided into four groups:
      group A, the control group, which was submitted to I/R injury only; group B, in
      which L-arginine was administered at a rate of 5 mg/kg/min during ischemia and
      continuing throughout reperfusion; group C, in which aprotinin was administered
      with an initial bolus dose of 20,000 U/kg during ischemia followed by a
      continuous dose at 50 U/hour throughout reperfusion; and group D in which both
      substances were administered. In all groups TNF-alpha, IL-1, and IL-6 levels were
      measured using ELISA at baseline, 2 hours of ischemia, and 1 hour and 2 hours of
      reperfusion. SMA blood flow was measured with a Doppler probe at baseline, 10
      min, 1 hour, and 2 hours of reperfusion. Histological changes of the intestinal
      mucosa were examined and graded on a five-point scale in all groups. RESULTS: In
      the control group, levels of TNF-alpha, IL-1, and IL-6 were significantly
      increased during reperfusion (p < 0.05) compared to baseline. Administration of L
      arginine and aprotinin led to suppression of the release of TNF-alpha, IL-1, and
      IL-6 during reperfusion in a statistically significant manner (all p < 0.05). A
      synergistic or additive effect of L-arginine and aprotinin was not observed. SMA
      blood flow in the control group was decreased (p > 0.05) during reperfusion
      compared to baseline. In animals treated with L-arginine and aprotinin, SMA blood
      flow during reperfusion was significantly increased (p < 0.05) compared to the
      control group. Histologic examination of the intestinal mucosa was characterized
      by flattening of the villi and necrosis in the control group. In the treated
      animals, less severe histological changes were noted. CONCLUSIONS: Administration
      of L: -arginine and aprotinin may lead to amelioration of intestinal I/R injury.
      We did not note a synergistic or additive effect of these two substances. These
      findings warrant further studies in clinical settings for future treatment
      efforts.

PMID- 17458595
TI  - Rates and patterns of recurrence for percutaneous radiofrequency ablation and
      open wedge resection for solitary colorectal liver metastasis.
AB  - INTRODUCTION: The purpose of this study was to compare rates and patterns of
      disease progression following percutaneous, image-guided radiofrequency ablation
      (RFA) and nonanatomic wedge resection for solitary colorectal liver metastases.
      METHODS: We identified 30 patients who underwent nonanatomic wedge resection for
      solitary liver metastases and 22 patients who underwent percutaneous RFA because
      of prior major hepatectomy (50%), major medical comorbidities (41%), or relative
      unresectability (9%). Serial imaging studies were retrospectively reviewed for
      evidence of local tumor progression. RESULTS: Patients in the RFA group were more
      likely to have undergone prior liver resection, to have a disease-free interval
      greater than 1 year, and to have had an abnormal carcinoembryonic antigen (CEA)
      level before treatment. Two-year local tumor progression-free survival (PFS) was
      88% in the Wedge group and 41% in the RFA group. Two patients in the RFA group
      underwent re-ablation, and two patients underwent resection to improve the 2-year
      local tumor disease-free survival to 55%. Approximately 30% of patients in each
      group presented with distant metastasis as a component of their first recurrence.
      Median overall survival from the time of resection was 80 months in the Wedge
      group vs 31 months in the RFA group. However, overall survival from the time of
      treatment of the colorectal primary was not significantly different between the
      two groups. CONCLUSIONS: Local tumor progression is common after percutaneous
      RFA. Surgical resection remains the gold standard treatment for patients who are
      candidates for resection. For patients who are poor candidates for resection, RFA
      may help to manage local disease, but close follow-up and retreatment are
      necessary to achieve optimal results.

PMID- 17458596
TI  - Hepatic artery chemoembolization in 122 patients with metastatic carcinoid tumor:
      lessons learned.
AB  - BACKGROUND: Hepatic artery chemoembolization (HACE) is a treatment option in the
      management of metastatic carcinoid. We reviewed our experience to identify
      potential factors that influence survival. METHODS: The records of 122 patients
      with metastatic carcinoid tumor undergoing HACE were reviewed. Log-rank analysis
      and Cox proportional hazards were applied to identify factors predictive of
      decreased survival. RESULTS: Median follow-up after HACE was 21.5 months.
      Complications occurred in 23% with periprocedural mortality of 5%. Radiographic
      tumor regression was seen in 82%, with stabilization of disease in 12%. Median
      duration of CT response was 19 months. Improvement in symptoms occurred in 92%
      for median duration of 13 months. HACE resulted in complete normalization of
      serum pancreastatin in 14%, with greater than 20% reduction in another 66%.
      Median overall survival was 33.3 months after HACE. Only pancreastatin level > or
      =5,000 pg/ml was associated with decreased survival by multivariate analysis.
      CONCLUSION: HACE offers symptom palliation and long-term survival in patients
      with incurable carcinoid metastases. Although safe, it should be approached
      cautiously in patients with significant tumor burden as evidenced by
      pancreastatin levels > or =5,000 pg/ml. We do not recommend whole-liver
      embolization in these patients but prefer a staged approach to each lobe of the
      liver.

PMID- 17458597
TI  - A 30-year analysis of colorectal adenocarcinoma in transplant recipients and
      proposal for altered screening.
AB  - PURPOSE: The risk of malignancy after solid-organ transplantation is well
      documented. However, the incidence and specific risk for colorectal
      adenocarcinoma, although previously proposed, has been difficult to calculate. We
      reviewed the University of Wisconsin transplant database for all cases of
      colorectal adenocarcinoma to assess the risk of this malignancy, as well as the
      need for improved screening in this population. METHODS: The transplant database
      was queried using diagnosis codes for colorectal adenocarcinoma to configure a
      list of eligible patients. Exclusion criteria included: age less than 18 years at
      the time of transplant, diagnosis of colorectal cancer or patient death less than
      12 months posttransplant, and pretransplant history of colorectal cancer or
      proctocolectomy. Statistical analysis determined overall incidence, age-specific
      incidence, and survival for this population. RESULTS: A total of 5,603 kidney,
      liver, or combination transplants were eligible for analysis from 1966 through
      2004. The mean follow-up was 9.3 years. We identified 40 cases of colorectal
      adenocarcinoma. Twenty-five of these cases (62%) occurred in kidney transplant
      recipients, 13 after liver transplant, and two after kidney-pancreas combination.
      Twenty-seven patients (68%) diagnosed with cancer have died, 12 of metastatic
      disease. The median survival postcancer diagnosis was 2.3 years. These results
      were compared to the National Cancer Institute Survival, Epidemiology, and End
      Results (SEER) database for colon and rectal cancer. The current age-adjusted
      annual incidence based on year 2000 census data is 0.053% (52.9/100,000), and the
      extrapolated 10-year incidence is 0.27%. The 10-year incidence in the
      transplanted cohort is 0.71% (incidence ratio = 2.6). The 5-year survival
      postcancer diagnosis is 63.5% in the general population (SEER), vs. 30.7% in the
      transplant cohort. The SEER median age at diagnosis of colorectal adenocarcinoma
      is 72.0 years. Of the transplant recipients who developed cancer, the median age
      at diagnosis was 58.7 years (32.4 to 78.2), and 11 patients (27%) were diagnosed
      at or before age 50. In the U.S. population, the annual incidence of colorectal
      adenocarcinoma below the age of 50 is 0.0055% (5.52/100,000) and the 10-year
      extrapolated incidence is 0.11%. The 10-year incidence in the under-50 transplant
      cohort is 0.33% (incidence ratio = 3.0). In this under-50 cohort, median time
      from transplant to cancer diagnosis was 7.8 years. CONCLUSION: The incidence of
      and 5-year survival after diagnosis of colorectal adenocarcinoma in transplant
      recipients is markedly different than the general population. Patients are often
      diagnosed at a younger age. With current screening guidelines, over 25% of at
      risk patients would not be screened. We propose modifying these guidelines to
      allow earlier detection of colorectal cancer in this population.

PMID- 17458598
TI  - Granulocyte colony-stimulating factor supports liver regeneration in a small-for
      size liver remnant mouse model.
AB  - Experimental partial hepatectomy of more than 80% of the liver weight bears an
      increased mortality in rodents, due to impaired hepatic regeneration in small-for
      size liver remnants. Granulocyte colony-stimulating factor (G-CSF) promotes
      progenitor cell expansion and mobilization and also has immunomodulatory
      properties. The aim of this study was to determine the effect of systemically
      administered G-CSF on liver regeneration and animal survival in a small-for-size
      liver remnant mouse model. Mice were preconditioned daily for 5 days with
      subcutaneous injections of 5 microg G-CSF or aqua ad injectabile. Subsequently,
      83% partial hepatectomy was performed by resecting the median, the left, the
      caudate, and the right inferior hepatic lobes in all animals. Daily sham or G-CSF
      injection was continued. Survival was significantly better in G-CSF-treated
      animals (P < 0.0001). At 36 and 48 h after microsurgical hepatic resection,
      markers of hepatic proliferation (Ki67, BrdU) were elevated in G-CSF-treated mice
      compared to sham injected control animals (P < 0.0001) and dry liver weight was
      increased (P < 0.05). G-CSF conditioning might prove to be useful in patients
      with small-for-size liver remnants after extended hepatic resections due to
      primary or secondary liver tumors or in the setting of split liver
      transplantation.

PMID- 17458599
TI  - Gastroesophageal reflux disease and obesity. Pathophysiology and implications for
      treatment.
AB  - Although the etiology of gastroesophageal reflux disease (GERD) is
      multifactorial, the pathophysiology of the disease in morbidly obese patients
      remains incompletely understood. The aims of this study were to compare in
      morbidly obese (body mass index (BMI) > or =35) and nonmorbidly patients (BMI
      <35) with GERD: (a) lower esophageal sphincter (LES) profile; (b) esophageal body
      function; and (c) esophageal acid exposure. We reviewed esophageal manometry and
      ambulatory 24-hour pH monitoring studies of 599 consecutive patients with GERD
      (DeMeester score >14.7). Patients were divided into two groups according to the
      BMI: (1) 520 patients (86.8%) with BMI <35 and (2) 79 patients (13.2%) with BMI >
      or =35. While the DeMeester score was not different between the two groups,
      morbidly obese patients had higher LES pressure and higher amplitude of
      peristalsis in the distal esophagus (DEA). Among these patients, LES and DEA
      pressures were often hypertensive. A linear regression model showed that BMI, LES
      pressure, LES abdominal length, and DEA were independently associated with the
      DeMeester score. These data showed that: (a) BMI was independently associated to
      the severity of GERD; and (b) in most morbidly obese patients with GERD, reflux
      occurred despite normal or hypertensive esophageal motility. These findings show
      that the pathophysiology of GERD in morbidly obese patients might differ from
      that of nonobese patients, suggesting the need for a different therapeutic
      approach.

PMID- 17458600
TI  - Internal hernias: clinical findings, management, and outcomes in 49 nonbariatric
      cases.
AB  - Internal hernia, the protrusion of a viscus through a peritoneal or mesenteric
      aperture, is a rare cause of small bowel obstruction. We report the clinical
      presentation, surgical management, and outcomes of one of the largest series of
      nonbariatric internal hernias. Ten-year retrospective review of patients at our
      institution yielded 49 cases of internal hernias. Majority of patients presented
      with symptoms of acute (75%) or intermittent (22%) small bowel obstruction. While
      16% of CT scans were suspicious for internal hernia, in no cases the preoperative
      diagnosis of internal hernia was made. The most frequent internal hernias were
      transmesenteric (57.0%) and 34 hernias (69%) were caused by previous surgery. All
      internal hernias were reduced and the defects were repaired. Compromised bowel
      was present in 22 cases and 11 patients underwent small bowel resection. The mean
      postoperative hospitalization was 10.9 days. The overall mortality rate from our
      series is 2%, and the morbidity rate is 12%. Transmesenteric hernias, as
      complications of previous surgeries, are the most prevalent internal hernias.
      Preoperative diagnosis of internal hernia is extremely difficult because of the
      nonspecific clinical presentation. However, if discovered promptly, internal
      hernias can be repaired with acceptable morbidity and mortality.

PMID- 17458601
TI  - Long-term results of a primary end-to-end anastomosis in peroperative detected
      bile duct injury.
AB  - The management of a bile duct injury detected during laparoscopic cholecystectomy
      is still under discussion. An end-to-end anastomosis (with or without T-tube
      drainage) in peroperative detected bile duct injury has been reported to be
      associated with stricture formation of the anastomosis area and recurrent
      jaundice. Between 1991 and 2005, 56 of a total of 500 bile duct injury patients
      were referred for treating complications after a primary end-to-end anastomosis.
      After referral, 43 (77%) patients were initially treated endoscopically or by
      percutaneous transhepatic stent placement (n = 3; 5%). After a mean follow-up of
      7 +/- 3.3 years, 37 patients (66%) were successfully treated with dilatation and
      endoscopically placed stents. One patient died due to a treatment-related
      complication. A total of 18 patients (32%) underwent a hepaticojejunostomy.
      Postoperative complications occurred in three patients (5%) without hospital
      mortality. These data confirm that end-to-end anastomosis might be considered as
      a primary treatment for peroperative detected transection of the bile duct
      without extensive tissue loss. Complications (stricture or leakage) can be
      adequately managed by endoscopic or percutaneous drainage the majority of
      patients (66%) and reconstructive surgery after complicated end-to-end
      anastomosis is a procedure with relative low morbidity and no mortality.

PMID- 17458602
TI  - Roux-en-Y drainage of the pancreatic stump decreases pancreatic fistula after
      distal pancreatic resection.
AB  - Clinically relevant fistula after distal pancreatic resection occurs in 5-30% of
      patients, prolonging recovery and considerably increasing in-hospital stay and
      costs. We tested whether routine drainage of the pancreatic stump into a Roux-en
      Y limb after distal pancreatic resection decreased the incidence of fistula. From
      October 2001, data of all patients undergoing pancreatic distal resection were
      entered in a prospective database. From June 2003 after resection, the main
      pancreatic duct and the pancreatic stump were oversewn, and in addition,
      anastomosed into a jejunal Roux-en-Y limb by a single-layer suture (n = 23). A
      drain was placed near the anastomosis, and all patients received octreotide for 5
      7 days postoperatively. The volume of the drained fluid was registered daily, and
      concentration of amylase was measured and recorded every other day. Patient
      demographics, hospital stay, pancreatic fistula incidence (> or =30 ml amylase
      rich fluid/day on/after postoperative day 10), perioperative morbidity, and
      follow-up after discharge were compared with our initial series of patients
      (treated October 2001-May 2003) who underwent oversewing only (n = 20).
      Indications, patient demographics, blood loss, and tolerance of an oral diet were
      similar. There were four (20%) pancreatic fistulas in the "oversewn" group and
      none in the anastomosis group (p < 0.05). Nonsurgical morbidity, in-hospital
      stay, and follow-up were comparable in both groups.

PMID- 17458603
TI  - Relief of dysphagia after laparoscopic Heller myotomy improves long-term quality
      of life.
AB  - BACKGROUND AND OBJECTIVE: Quality of life (QoL) is getting more attention in the
      medical literature. Treatment outcomes are now gauged by their effect on the QoL
      along with their direct effect on the diseases they are targeting. The aim of the
      study was to assess the impact of residual dysphagia on QoL after laparoscopic
      Heller myotomy for achalasia. METHODS: QoL was evaluated using the short-form-36
      (SF-36) and postoperative dysphagia was assessed using a dysphagia score. The
      score (range 0-10) was calculated by combining the frequency of dysphagia
      (0=never, 1 = < 1 day/wk, 2 = 1 day/wk, 3 = 2-3 days/wk, 4 = 4-6 days/wk,
      5=daily) with the severity (0=none, 1=very mild, 2=mild, 3=moderate, 4=moderately
      severe, 5=severe). Patients were classified in the Nonresponder group when their
      dysphagia score was in the upper quartile. RESULTS: Questionnaires were mailed to
      110 patients. The overall response rate was 91% with 100 patients (54 female)
      returning the questionnaires. The average follow-up was 3.3 years. There was a
      significative inverse correlation between dysphagia score and mental component (P
      = 0.0001) and total SF-36 (P = 0.001) scores. According to their postoperative
      dysphagia scores, 77 patients were assigned to the Responder Group and 23
      patients to the Nonresponder Group. The two groups were similar in terms of age,
      gender, rate of fundoplication, and length of follow-up. Mental component and
      total SF-36 scores were significantly (P < 0.05) higher in the Responder group.
      Successful relief of dysphagia after Heller myotomy was associated with health
      related quality of life scores that were 13 higher in Vitality (P < 0.05), 11
      points higher in mental health (P < 0.05), and 12 points higher in General Health
      (P < 0.05). Overall patient satisfaction with surgical outcome was 92%, with only
      eight patients not satisfied with the surgery. CONCLUSION: Laparoscopic Heller
      myotomy offers excellent long-term relief of achalasia-related symptoms, namely
      dysphagia, and this was projected on a significant improvement in quality of life
      and patient satisfaction.

PMID- 17458604
TI  - Preemptive total gastrectomy for hereditary gastric cancer.
AB  - Hereditary gastric cancer is a recently described clinical syndrome, associated
      with truncating mutation of the E-cadherin gene, named CDH1. It is characterized
      by autosomal dominant transmission, presentation at an early age, and with
      diffuse type of gastric adenocarcinoma. Clinical management of these patients is
      challenging and includes intense endoscopic surveillance or prophylactic
      gastrectomy, which is associated with short- and long-term morbidity. We report
      four patients submitted to a prophylactic gastrectomy performed in members of
      three families with hereditary gastric cancer in a tertiary referral center in
      Mexico City. These are the first Hispanic families with hereditary gastric cancer
      reported in the literature.

PMID- 17458606
TI  - Survival and variceal rehemorrhage after shunting support small-diameter
      prosthetic H-graft portacaval shunt.
AB  - This study was undertaken to report variceal rebleeding and survival after small
      diameter prosthetic H-graft portacaval shunts (HGPCS) and to compare actual to
      predicted survival after shunting. Since 1987 we have prospectively followed
      patients after undergoing HGPCS to treat bleeding varices failing/not amenable to
      sclerotherapy/banding. One hundred and seventy patients underwent shunting.
      Cirrhosis was because of alcohol in 56%, hepatitis in 12%, both in 11%, and other
      causes in 21%. Child class was A for 10%, B for 28%, and C for 62%. Thirty-three
      patients died by 6 months, 54 by 24 months, 87 by 60 months, and 112 by 10 years,
      generally because of liver failure. Fifty-one patients are alive at a median of
      48.3 months, 76 months +/- 57.8 (mean +/- SD). Variceal rehemorrhage was
      documented in 3 (2%) patients. By child class, 5-year/10-year survival rates were
      as follows: A 66.7/33.3%, B 48.6/15.6%, and C 29.2/7.0%. Actual survival was
      superior to predicted survival (Model for End-Stage Liver Disease [MELD]), (p <
      0.001). Variceal rehemorrhage in patients undergoing small-diameter prosthetic H
      graft portacaval shunting was very uncommon. Actual survival was superior to
      predicted survival (MELD). Long-term survival paralleled degree of hepatic
      function, although long-term survival was possible even with very advanced
      cirrhosis. Application of HGPCS is encouraged.

PMID- 17458605
TI  - Liver resection for primarily unresectable colorectal metastases downsized by
      chemotherapy.
AB  - This study was performed prospectively to assess the effect of systemic
      chemotherapy (FOLFIRI protocol) in patients with initially unresectable
      colorectal liver metastases (CRLM) and, after performing liver resection in
      patients with downsized metastases, to compare the postoperative and long-term
      results with those of patients with primarily resectable CRLM. Records from a
      prospective database including all consecutive admissions for CRLM between June
      2000 and June 2004 were reviewed. The analysis addressed all patients who
      underwent hepatectomy for primarily resectable CRLM (Group A), or underwent
      chemotherapy for primarily unresectable CRLM and among these, particularly the
      patients who were finally resected after downsizing of CRLM (Group B). There were
      60 primarily resected patients (Group A). Forty-two other patients underwent
      chemotherapy; after an average of nine courses, 18 of them (42.8%) with
      significantly downsized lesions were explored and 15 (35.7%, Group B) were
      resected, whereas three had peritoneal metastases. Group B differed from Group A
      for a significantly higher rate of synchronous CRLM upon diagnosis of colorectal
      cancer, a larger size of CRLM upon evaluation in our center, and a lower rate of
      major hepatectomies (20.0% vs. 51.6 %) at surgery. No patient in Group B had
      positive margins of resection. Operative mortality was nil and morbidity was
      20.0% in both groups. In Group B vs. Group A median survival after hepatectomy
      was 46 vs. 47 months (n.s), 3-year survival rate was 73% vs. 71% (n.s.), disease
      free survival rate was 31% vs. 58% (p = 0.04) and, at a median follow-up of 34
      months, tumor recurrence rate was 53.3% vs. 28.3% (n.s.). Four out of the eight
      Group B patients with recurrence underwent a re-resection, and were alive at 9 to
      67 months after the first resection. These results show that in about one-third
      of the patients with primarily unresectable CRLM, downsizing of the lesions by
      chemotherapy (FOLFIRI protocol) permitted a subsequent curative resection. In
      these patients, operative risk and survival did not differ from the figures
      observed in primarily resectable patients and, in spite of a lower disease-free
      survival with more frequent recurrence, re-resection still represented a valid
      option to continue treatment.

PMID- 17458607
TI  - Portal vein stenting for portal hypertension caused by local recurrence after
      pancreatoduodenectomy for periampullary cancer.
AB  - Portal hypertension after extensive abdominal surgery is an unusual cause of
      repetitive gastrointestinal bleeding. We report on a 68-year-old male patient
      with intermittent gastrointestinal bleeding secondary to portal vein stenosis
      caused by local recurrence of the distal bile duct cancer after
      pancreatoduodenectomy. Severe portal vein stenosis without sufficient development
      of portal venous collaterals was detected 25 months after pancreatoduodenectomy.
      Direct portography using a percutaneous transhepatic approach showed that there
      was a pressure gradient of 18 mmHg across the portal vein stenosis. Portal vein
      stenting successfully relieved portal hypertension and bowel congestion.
      Gastrointestinal bleeding episodes ceased after stenting. The patient died from
      liver metastasis 14 months after stent insertion and 39 months after
      pancreatoduodenectomy. Based on this case and literature reports, the possibility
      of portal vein stenosis should be considered for patients who have undergone
      pancreatoduodenectomy and then showed unexplained gastrointestinal bleeding.
      Percutaneous transhepatic stent insertion appears to be the treatment of choice
      for focal portal vein stenosis.

PMID- 17458608
TI  - Predictive factors of malignant or invasive intraductal papillary-mucinous
      neoplasms of the pancreas.
AB  - The aim of this study was to identify useful preoperative diagnostic findings
      indicative of malignant or invasive intraductal papillary-mucinous neoplasms
      (IPMN) of the pancreas to determine an optimal operative procedure for IPMN.
      Sixty-two IPMNs, which consisted of 29 adenomas, 10 borderline tumors, 11
      adenocarcinomas in situ, and invasive adenocarcinomas were reviewed from 1990 to
      2003. Preoperative predictive factors of malignant or invasive IPMN were analyzed
      among 10 factors by univariate and multivariate analysis. Diameter of the main
      pancreatic duct (> or =6 mm) and cytological examination of the pancreatic juice
      (the presence of malignant cells) were identified as independent predictive
      factors of malignant IPMN, and only cytological examination of the pancreatic
      juice (the presence of malignant cells) was identified as an independent
      predictor of invasive IPMN by multivariate analysis (P < 0.05). There was no
      recurrent disease in patients with adenoma and adenocarcinoma in situ, whereas
      recurrences occurred in 6 of 12 patients with invasive IPMN. Patient survival in
      noninvasive IPMN was significantly (P = 0.018) better than that in invasive IPMN
      (The overall 5-year survival rates were 87.2% and 49.2%, respectively). These
      results might be useful for selecting an optimal surgical procedure for IPMN.

PMID- 17458609
TI  - Staple line reinforcement reduces postoperative pancreatic stump leak after
      distal pancreatectomy.
AB  - Pancreatic stump leak is the major source of morbidity after stapled distal
      pancreatectomy. We hypothesized that reinforcement of the stapler system with a
      buttress mat can improve leak rates when compared to standard stapling alone. We
      performed 13 consecutive distal pancreatectomies using our reinforced stapler
      system, forming our experimental group. A historical control group was composed
      of 18 patients undergoing stapled pancreatic closure without reinforcement. The
      main outcome measure was pancreatic leak in the postoperative period. Pancreatic
      leaks included fistulas and fluid collections (sterile or infected). Hospital
      length of stay was recorded as a secondary measure. Postoperative pancreatic leak
      rate was zero in the experimental group, but 39% in the control group (P =
      0.025). Development of a pancreatic leak resulted in prolonged hospital stays:
      13.6 vs 8.3 days (P < 0.03). We conclude that staple line reinforcement is a
      simple and effective method of reducing pancreatic stump leakage after distal
      pancreatectomy. The economic impact of lower leak rates is reflected in
      significantly shorter hospital stays. The results of our study should be
      validated in a randomized controlled trial.

PMID- 17458610
TI  - Impact of lymph node involvement on long-term survival after R0
      pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas.
AB  - Pancreaticoduodenectomy remains the only potentially curative treatment for
      adenocarcinoma of the pancreas. The aim of this study was to analyze prognostic
      factors impacting survival after R0 pancreaticoduodenectomy for adenocarcinoma in
      the head of the pancreas. Between 1995 and 2002, a potentially curative (R0)
      pancreaticoduodenectomy with pancreatogastrostomy for ductal adenocarcinoma in
      the head of the pancreas was performed in 81 patients (42 women and 39 men) with
      a mean age of 64 years (range 35-84). Patients were identified from a prospective
      database and records were reviewed retrospectively. Postoperative mortality was
      1%, and 40% of patients had complications. Median survival was 18 months, and the
      5-year survival was 24%. Fifteen patients were alive at 5 years. Factors
      associated with poor survival in multivariate analysis were (1) two or more
      positive lymph nodes, (2) tumor diameter greater than 30 mm, and (3) age greater
      than 70 years. In patients with no or with one positive lymph node, the 5-year
      survival was 44%. On the other hand, in patients with two or more positive lymph
      nodes, both the 3- and 5-year survival was 5%. The main risk factor associated
      with poor survival after an R0 pancreaticoduodenectomy for adenocarcinoma in the
      head of pancreas was lymph node status: The presence of two or more positive
      lymph nodes was associated with decreased survival.

PMID- 17458611
TI  - Treatment of acute pancreatic pseudocysts after severe acute pancreatitis.
AB  - Treatment of acute pancreatic pseudocysts (APP) after an episode of severe acute
      pancreatitis (SAP) remains controversial. Both population heterogeneity and
      limited numbers of patients in most series prevent a proper analysis of
      therapeutic results. The study design is a case series of a large, tertiary
      referral hospital in the surgical treatment of patients with APP after SAP. An
      institutional treatment algorithm was used to triage patients with complicated
      APP and organ failure based on Sequential Organ Failure Assessment scores to
      temporizing percutaneous or endoscopic drainage to control sepsis and improve
      their clinical condition before definitive surgical management. Over a 10-year
      period of study (December 1995 to 2005), 73 patients with APP after an episode of
      SAP were treated, 43 patients (59%) developed complications (infection 74.4%,
      perforation 21%, and bleeding 4.6%) and qualified for our treatment algorithm.
      Percutaneous/endoscopic drainage was successful in controlling sepsis in 11 of 13
      patients (85%) with severe organ failure and allowed all patients to undergo
      definitive surgical management. The morbidity (7 vs 44.1%, P = 0.005) and
      mortality rates (0 vs 19%, P = 0.04) were significantly higher in complicated vs
      uncomplicated APP. Acute pancreatic pseudocysts after SAP are unpredictable and
      have a high incidence of complications. Once complications develop, there is a
      significantly higher morbidity and mortality rate. In complicated APP with severe
      organ failure, percutaneous/endoscopic drainage is useful in controlling sepsis
      and allowing definitive surgical management.

PMID- 17458612
TI  - The Dagradi-Serio-Iacono operation central pancreatectomy.
AB  - Central pancreatectomy (CP) is a segmental pancreatic resection indicated to
      remove benign or low-grade malignant tumors of the isthmus and proximal part of
      the body of the pancreas. The main advantage of this operation compared with
      major resections is that it permits to spare normal pancreatic parenchyma;
      moreover, spleen and upper digestive and biliary tracts are saved. The
      description of the complete operation was reported for the first time by Dagradi
      and Serio in 1984 and subsequently spread worldwide by Iacono and Serio. In our
      opinion, it should be called the Dagradi-Serio-Iacono operation, by the names of
      the surgeons who first performed it (Dagradi and Serio), and by the names of the
      surgeons responsible for reporting it worldwide with precise indications (Iacono
      and Serio). Operation requires a midline or a bilateral subcostal incision; the
      lesser sac is entered through dissection of the transverse colon from the omentum
      or by transecting the gastrocolic ligament. The pancreatic segment harboring the
      lesion is then mobilized and its posterior surface carefully dissected from the
      splenic vein and artery. Subsequently, the pancreatic portion harboring the tumor
      is isolated at its superior margin from the splenic artery after the pancreas is
      transacted. The extent of the resection of the central segment is limited on the
      right by the gastroduodenal artery and on the left by the need to leave at least
      5 cm of normal pancreatic remnant. The resected pancreatic specimen is sent to
      the pathologist for confirmation of diagnosis and to check if the resection
      margins are adequate. Hemostasis of the two raw surfaces is achieved with
      interrupted 5 or 4/0 nonabsorbable stitches. When it is not stapled, the
      Wirsung's duct of the cephalic stump is sutured selectively with a figure-of
      eight nonabsorbable stitch. An end-to-end invaginated pancreaticojejunostomy is
      carried out with a single layer of interrupted stitches. The operation is
      concluded with the construction of an end-to-side jejuno-jejunostomy about 50 cm
      distal to the pancreatic anastomosis. Other techniques for reconstruction of the
      distal stump using jejunum or stomach have been described. One or two soft drains
      are brought out on the right side. The fluid collected from this drain is checked
      for amylase level on postoperative days 3, 5, and 7; if the level is low or
      absent, the drain is removed. Central pancreatectomy is a safe technique for
      benign or low malignant tumors of the pancreatic neck that allows curing the
      tumor with evident functional results without increasing the risk for the
      patient. We can say that CP has a clear role like pancreaticoduodenectomy and
      distal pancreatectomy and we think that a pancreatic surgeon has to include this
      procedure in his/her technical skills. In order to obtain excellent results,
      correct indications and experience in pancreatic surgery are recommended.

PMID- 17458614
TI  - Intrahepatic cholangiocarcinoma mimicking hepatic inflammatory pseudotumor.
AB  - A 50-year-old male with hepatitis B was referred for a small intrahepatic nodule.
      Magnetic resonance images raised strong suspicion of a benign lesion, such as an
      inflammatory pseudotumor, while the other radiological studies were equivocal.
      Furthermore, the high-intensity image on diffusion magnified-weighted imaging
      with a low B value strongly suggested a benign tumor. In spite of the absence of
      typical clinical or radiological findings, needle biopsy revealed an intrahepatic
      cholangiocarcinoma (ICC). The diagnosis of peripheral ICC rich in fibrous tissue
      seems to require needle biopsy for pathological examination with
      immunohistochemical staining because it frequently mimics other diseases,
      including benign tumors.

PMID- 17458613
TI  - Surgery for obesity: a review of the current state of the art and future
      directions.
AB  - The number of patients undergoing surgery for the treatment of obesity, and the
      proportion of the health care budget dedicated to this health problem, is growing
      exponentially. There are several competing surgical approaches for the management
      of morbid obesity. We review the literature relating to four of these: gastric
      bypass, biliopancreatic diversion, gastric banding, and gastric pacing. Our
      review finds that while enhancing the malabsorptive activity of these procedures
      may induce an incremental increase in excess body weight loss, the proportion of
      patients who fail to lose more than 50% of their excess body weight is similar no
      matter how radical is the surgery performed. There is little guidance from the
      literature as to appropriate patient selection for the varying procedures, and
      anonymously reported registries have yet to show that patients who undergo
      bariatric surgery have enhanced longevity. To date, the bariatric surgical
      community has not conducted adequately powered randomized prospective trials to
      elucidate key elements of the surgical procedure such as optimal bypass length,
      to determine whether mixed operations are superior to those that offer intake
      restriction only, and to define what constitutes success after bariatric surgery.
      As a public health measure, bariatric surgery in the United States is being
      pursued in an irrational manner, being concentrated in areas where there are
      fewer morbidly obese patients, and used disproportionately among the population
      of white obese females.

PMID- 17458615
TI  - Prosthetic mesh repair of large and recurrent diaphragmatic hernias.
AB  - BACKGROUND: Laparoscopic repair of large paraesophageal hernias (PEH) is
      associated with significant recurrence rates. Use of prosthetic mesh to complete
      tension-free repair of the hiatus has been suggested to decrease the recurrence
      rate. METHODS: Fifty-nine patients with large (n = 44) or recurrent (n = 15) PEH
      were operated on via the laparoscopic approach with the use of prosthetic mesh.
      Patients were followed with office visits and phone interviews. All patients were
      referred for barium studies. Data analysis included all patients, including
      conversions, on an intention-to-treat basis. RESULTS: Followup was completed in
      56 (95%) patients. Mean followup time was 28.4 months. Forty patients (74%) had
      significant relief of all symptoms. Barium studies were performed in 45 patients
      (80.3%), including all symptomatic patients. Fifteen patients (33%) had a small
      sliding hernia, six (13.3%) had recurrent PEH, and four (8.8%) had narrowing of
      the gastroesophageal junction. Most patients with small hiatal hernias were
      symptomatic (60%). All responded to medical treatment. CONCLUSIONS: Laparoscopic
      repair of large PEH with reinforcement mesh is feasible and safe with excellent
      short-term results. Long-term followup shows a low PEH recurrence requiring
      reoperation, but a significant number of patients develop symptomatic recurrent
      small hiatal hernias that can be managed nonoperatively.

PMID- 17458616
TI  - A pilot study of botulinum toxin injection for the treatment of delayed gastric
      emptying following esophagectomy.
AB  - OBJECTIVE: Esophagectomy may lead to impairment in gastric emptying, unless a
      pyloroplasty or pyloromyotomy is performed. These procedures may be technically
      challenging during minimally invasive esophagectomy, and they are associated with
      a small but definable morbidity, such as leakage and dumping syndrome. We sought
      to determine the results of our early experience with injecting the pylorus with
      botulinum toxin instead of conventional pyloric drainage. METHODS: Fifteen
      patients who had undergone esophagectomy and injection of the pylorus with
      botulinum toxin were identified. Twelve patients had undergone botulinum toxin
      injection at the time of minimally invasive esophagectomy, and the remaining
      three had been treated endoscopically after surgery. The latter three patients
      had undergone esophagectomy with either no pyloric drainage (n = 2) or an
      inadequate pyloromyotomy (n = 1), and they presented in the postoperative period
      with delayed gastric emptying. The adequacy of emptying after injection was
      assessed by the patients' ability to tolerate a regular diet, a barium swallow,
      and a nuclear gastric emptying study. RESULTS: No patient injected with botulinum
      toxin during esophagectomy developed delayed gastric emptying or aspiration
      pneumonia in the perioperative period. Eight of these patients underwent a
      nuclear emptying scan at a median of 4.2 months after surgery, which showed a
      mean emptying half-life of 100 min. With a median follow-up of 5.3 months, one
      patient (8%) required reintervention for symptoms of gastric stasis, presumably
      after the effect of the toxin subsided. All three patients injected
      postoperatively demonstrated an improvement in symptoms of gastric outlet
      obstruction and were able to resume a regular diet. CONCLUSIONS: Injection of the
      pylorus with botulinum toxin can be performed safely in patients undergoing
      esophagectomy. Longer-term studies are needed to clarify the efficacy and
      durability of this technique compared to the accepted procedures of pyloromyotomy
      or pyloroplasty.

PMID- 17458618
TI  - The use of ultrasound in the diagnosis of abdominal wall hernias.
AB  - BACKGROUND: The diagnosis of abdominal wall hernias is not always straightforward
      and may require additional investigative modalities. Real-time ultrasound is
      accurate, non-invasive, relatively inexpensive, and readily available. The value
      of ultrasound as an adjunctive tool in the diagnosis of abdominal wall hernias in
      both pre-operative and post-operative patients was studied. STUDY DESIGN:
      Retrospective analysis of 200 patients treated at the Hernia Institute of Florida
      was carried out. In these cases, ultrasound had been used to assist with case
      management. Patients without previous hernia surgery and those with early and
      late post-herniorrhaphy complaints were studied. Patients with obvious hernias
      were excluded. Indications for ultrasound examination included patients with
      abdominal pain without a palpable hernia, a palpable mass of questionable
      etiology, and patients with inordinate pain or excessive swelling during the
      early post-operative period. Patients were treated with surgery or conservative
      therapy depending on the results of the physical examination and ultrasound
      studies. Cases in which the ultrasound findings influenced the decision-making
      process by confirming clinical findings or altering the diagnosis and changing
      the treatment plan are discussed. RESULTS: Of the 200 patients, 144 complained of
      pain alone and on physical exam no hernia or mass was palpable. Of these 144
      patients with pain alone, 21 had a hernia identified on the US examination and
      were referred for surgery. The 108 that had a negative ultrasound were treated
      conservatively with rest, heat, and anti-inflammatory drugs, most often with
      excellent results. Of the 56 remaining patients who had a mass, with or without
      pain, 22 had hernias identified by means of ultrasound examination. In the other
      34, the etiology of the mass was not a hernia. CONCLUSIONS: Abdominal wall
      ultrasound is a valuable tool in the scheme of management of patients in whom the
      diagnosis of abdominal wall hernia is unclear. Therapeutic decisions can be
      influenced by the ultrasound findings that can provide more efficient and
      economical treatment by expediting their clinical management.

PMID- 17458619
TI  - Analysis of HIV-1 CRF07_BC gag p6 sequences indicating novel deletions in the
      central region of p6.
AB  - We amplified gag sequences from 66 individuals infected with HIV-1 CRF07_BC
      during 2003-2005 in the Xinjiang region of China. A novel deletion of 7aa
      (including a KELY motif) in the central region of the CRF07_BC gag p6 domain was
      detected, which has not been reported in other HIV-1 subtypes. Further deletions
      of up to 13aa (including KQE and KELY motifs) was also found in this domain,
      representing the biggest natural deletion up to now. Moreover, the CD4+ count and
      viral load level indicated that 1-13aa deletions in CRF07_BC gag p6 do not have a
      significant effect on viral replication and fitness.

PMID- 17458620
TI  - The '6K1' protein of a strain of Soybean mosaic virus localizes to the cell
      periphery.
AB  - The '6K1' protein of the Pinellia isolate of Soybean mosaic virus was cloned into
      a prokaryotic expression vector and a polyclonal antiserum raised to the
      expressed fusion protein. In immunogold labeling of thin sections of infected
      leaves of Pinellia ternata, specific labeling occurred at the cell periphery.
      This might suggest that the potyvirus '6K1' protein plays some role in viral cell
      to-cell movement but the lack of transmembrane domains suggests that it does not
      conform to currently-recognized patterns of viral movement proteins.

PMID- 17458621
TI  - Antigenic characterization of phocine distemper virus causing mass mortality in
      2002 and its relationship to other morbilliviruses.
AB  - The antigenic relationship between the phocine distemper virus (PDV) strain
      causing the epidemic in 2002 and the PDV strain of 1988, canine distemper virus
      from two dogs and one marten, and one measles virus strain was investigated in
      vivo and in vitro using monospecific polyclonal and monoclonal antibodies
      directed against five different proteins of canine or phocine distemper virus (N,
      P, M, F, H). Epitopic mapping revealed no difference between the PDV strains
      causing the epidemics in 1988 or 2002. However, the use of these antibodies
      allowed discrimination between different morbilliviruses including a vaccine
      strain of canine distemper virus. The major differences among the investigated
      morbilliviruses were found in the H protein.

PMID- 17458622
TI  - The chloroxoquinolinic derivative 6-chloro-1,4-dihydro-4-oxo-1-(beta-D
      ribofuranosyl) quinoline-3-carboxylic acid inhibits HSV-1 adsorption by impairing
      its adsorption on HVEM.
AB  - In this paper, we describe that the oxoquinolinic acid derivative (compound A)
      inhibited HSV-1 adsorption on Vero cells. This effect was achieved with an EC(50)
      value of 10 +/- 2.0 microM and with low cytotoxicity, since the CC(50) value for
      compound A was >1000 microM. Moreover, we demonstrate for the first time that
      adsorption inhibition was due to the blockage of the interactions between HSV-1
      and the cellular receptor herpes virus entry mediator (HVEM). These results show
      that compound A can prevent HSV-1 infection in Vero cells, encouraging further
      studies to determine at what level compound A inhibits HSV-1-HVEM interactions.

PMID- 17458623
TI  - Cytoplasmic/nuclear localization of tuberin in different cell lines.
AB  - Tuberous sclerosis (TSC) is an autosomal dominantly inherited disease affecting 1
      in 6000 individuals. The TSC gene products, hamartin and tuberin, form a complex,
      of which tuberin is assumed to be the functional component being involved in a
      wide variety of different cellular processes. Tuberin has been demonstrated to be
      localized to both, the cytoplasm and the nucleus. The cytoplasmic/nuclear
      localization of tuberin is known to be regulated by the serine/threonine protein
      kinase Akt. Akt also regulates the cytoplasmic/nuclear localization of the cyclin
      dependent kinase inhibitor p27. In this study the localization of these two Akt
      regulated proteins was analysed in different cell lines.

PMID- 17458624
TI  - Sub-epitopic dissection of HCV E1315-328HRMAWDMMMNWSPT sequence by similarity
      analysis.
AB  - Our labs are focused on identifying amino acid sequences having the ability to
      react specifically with the functional binding site of a complementary antibody.
      Our epitopic definition is based on the analysis of the similarity level of
      antigenic amino acid sequences to the host proteome. Here, the similarity profile
      to the human proteome of an HCV E1 immunodominant epitope, i.e. the HCV E1(315
      328)HRMAWDMMMNWSPT sequence, led to i) characterizing the immunoreactive HCV E1
      315-328 region as a sequence endowed with a low level of similarity to human
      proteins; ii) defining 2 contiguous immunodominant linear determinants
      respectively located at the NH(2) and COOH terminus of the conserved viral
      antigenic sequence. This study supports the hypothesis that low sequence
      similarity to the host's proteome modulates the pool of epitopic amino acid
      sequences in a viral antigen, and appears of potential value in defining
      immunogenic viral peptide sequences to be used in immunotherapeutic approaches
      for HCV treatment.

PMID- 17458625
TI  - Teaching empathy, learning about equanimity.

PMID- 17458626
TI  - Contribution of shame and attribution style in developing PTSD among Japanese
      University women with negative sexual experiences.
AB  - The roles of shame and attribution style in developing posttraumatic stress
      disorder (PTSD) were examined among 172 Japanese university women with negative
      sexual experiences (NSEs) using a structural equation model. "Shame" directly
      predicted PTSD, whereas "Internal Attribution" and "External Attribution" did
      not. The effect of Internal Attribution on PTSD was mediated by Shame. In a
      simultaneous analysis of multi-groups, only the relationship with the perpetrator
      showed a different contribution for shame in developing PTSD symptoms. In
      addition, the role of the shame and attribution style in developing PTSD symptoms
      in the Japanese culture was discussed.

PMID- 17458627
TI  - The plant cytoskeleton - new jobs for a versatile network.

PMID- 17458628
TI  - Recent progress in living cell imaging of plant cytoskeleton and vacuole using
      fluorescent-protein transgenic lines and three-dimensional imaging.
AB  - In higher-plant cells, microtubules, actin microfilaments, and vacuoles play
      important roles in a variety of cellular events, including cell division,
      morphogenesis, and cell differentiation. These intracellular structures undergo
      dynamic changes in their shapes and functions during cell division and
      differentiation, and to analyse these sequential structural changes, the vital
      labelling technique, using the green-fluorescent protein or other fluorescent
      proteins, has commonly been used to follow the localisation and translocation of
      specific proteins. To visualise microtubules, actin filaments, and vacuoles,
      several strategies are available for selecting the appropriate fluorescent
      protein fusion partner: microtubule-binding proteins, tubulin, and plus-end
      tracking proteins are most suitable for microtubule labelling; the actin binding
      domain of mouse talin and plant fimbrin for actin microfilament visualisation;
      and the tonoplast-intrinsic proteins and syntaxin-related proteins for vacuolar
      imaging. In addition, three-dimensional reconstruction methods are indispensable
      for localising the widely distributed organelles within the cell. The maximum
      intensity projection method is suitable for cytoskeletal structures, while
      contour-based surface modelling possesses many advantages for vacuolar membranes.
      In this article, we summarise the recent progress in living cell imaging of the
      plant cytoskeleton and vacuoles using various fusions with green-fluorescent
      proteins and three-dimensional imaging techniques.

PMID- 17458629
TI  - Actin-filament-dependent remodeling of the vacuole in cultured mesophyll
      protoplasts.
AB  - The ability of plant cells to dedifferentiate represents an important survival
      strategy invoked in a range of situations from repair mechanisms following
      wounding to apomixis. Dedifferentiation requires that somatic cells reprogram and
      enter the cell division cycle. This in turn necessitates the accurate
      partitioning of nuclear content and organelles, such as chloroplasts, to daughter
      cells, thereby ensuring continuity of cellular information systems. The
      distribution of cytoplasm and its organelle content in mature plant cells is
      governed by a large, central vacuole, with connections between distant cortical
      and perinuclear cytoplasmic domains mediated by transvacuolar strands. Here we
      examined the changes to vacuolar architecture in Arabidopsis thaliana protoplasts
      expressing a green-fluorescent protein fusion to a delta-tonoplast-intrinsic
      protein (deltaTIP). We found that vacuolar architecture became increasingly
      intricate during protoplast culture with the development of numerous
      transvacuolar strands. The development of an intricate vacuolar architecture was
      an actin filament- and not microtubule-dependent process, as is the case in
      interphase plant cells. Furthermore, we show that myosin is required for this
      increased complexity of vacuolar architecture and the formation of subcortical
      actin filament arrays. Despite the likelihood that increased vacuolar
      invagination would allow better redistribution of cytoplasmic organelles, we
      found that repositioning of chloroplasts from cortical to perinuclear cytoplasm
      was not dependent on transvacuolar strands. Our findings indicate that the
      vacuole is a dynamic entity that develops a complex architecture before
      dedifferentiating plant cells enter cell division.

PMID- 17458630
TI  - Development-specific association of amyloplasts with microtubules in scale cells
      of Narcissus tazetta.
AB  - Narcissus tazetta is one of the major geophyte crops worldwide, but little is
      known about its cell biology. The narcissus storage organ was studied by
      monitoring scale cell biology during the growth stage and dormancy, and it was
      found that amyloplasts gradually increased in size and reached a maximum at
      dormancy. In parallel, microtubules changed their organisation: during the growth
      phase (February to March) they were oblique; during April and May, microtubules
      formed a network with round "holes"; by late June and the beginning of July, when
      dormancy started, they were organised in parallel arrays. The holes formed in the
      microtubule array corresponded to amyloplasts. A closer look showed that during a
      short time window, while the plants were preparing for dormancy, the microtubules
      surrounded the amyloplasts. In vitro reconfirmation of this phenomenon was
      obtained when fluorescent bovine brain microtubules enwrapped isolated
      amyloplasts that had been purified between April and July but not those purified
      between January and March. Interestingly, protease treatment of amyloplasts did
      not completely prevent binding of microtubules, which suggests the existence of a
      protease-resistant factor that docks microtubules to the outer membrane of
      amyloplasts.

PMID- 17458631
TI  - Myosin inhibitors block accumulation movement of chloroplasts in Arabidopsis
      thaliana leaf cells.
AB  - Chloroplasts alter their distribution within plant cells depending on the
      external light conditions. Myosin inhibitors 2,3-butanedione monoxime (BDM), N
      ethylmaleimide (NEM), and 1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4
      diazepine hydrochloride (ML-7) were used to study the possible role of myosins in
      chloroplast photorelocation in Arabidopsis thaliana mesophyll cells. None of
      these agents had an effect on the chloroplast high-fluence-rate avoidance
      movement but all of the three myosin inhibitors blocked the accumulation movement
      of chloroplasts after a high-fluence-rate irradiation of the leaves. The results
      suggest that myosins have a role in A. thaliana chloroplast photorelocation.

PMID- 17458632
TI  - The function of actin-binding proteins in pollen tube growth.
AB  - Pollen tube growth is a key step in sexual reproduction of higher plants. The
      pollen tube is a typical example of tip-growing cells and shows a polarized
      cytoplasm. To develop and maintain polarized growth, pollen tubes need a
      carefully regulated actin cytoskeleton. It is well known that actin-binding
      proteins are responsible for the direct control of dynamic actin filaments and
      serve as a link between signal transduction pathways and dynamic actin changes in
      determining cellular architecture. Several of these classes have been identified
      in pollen tubes and their detailed characterisation is progressing rapidly. Here,
      we aim to survey what is known about the major actin-binding proteins that affect
      actin assembly and dynamics, and their higher-order organisation in pollen tube
      growth.

PMID- 17458633
TI  - Reversible protein tyrosine phosphorylation affects pollen germination and pollen
      tube growth via the actin cytoskeleton.
AB  - Phenylarsine oxide (PAO) and genistein are two well-known specific inhibitors of
      tyrosine phosphatases and kinases, respectively, that have been used in the
      functional analysis of the status of protein phosphotyrosine in different cell
      types. Our experiments showed that both PAO and genistein arrested pollen
      germination and pollen tube growth and led to the malformation of the pollen
      tubes, although genistein had a lesser effect. The malformations of the pollen
      tubes caused by PAO and genistein were, however, quite different. In addition, it
      was found that the rate of pollen germination and tube growth recovered to a
      certain extent when phalloidin was present during PAO treatment, but not when it
      was present during genistein treatment. Furthermore, PAO treatment also had a
      great effect on the dynamic organization of filamentous actin in the pollen grain
      and pollen tube, while genistein only caused reorganization of actin at the
      turning point of the pollen tube. Our results suggest that reversible protein
      tyrosine phosphorylation is a crucial step in pollen germination and pollen tube
      growth, but that tyrosine kinases and phosphatases may have different effects
      which may function through the reorganization of the actin cytoskeleton.

PMID- 17458634
TI  - Arabidopsis thaliana myosin XIK is involved in root hair as well as trichome
      morphogenesis on stems and leaves.
AB  - Myosins form a large superfamily of molecular motors that move along actin
      filaments. The functions of myosins in plant cells are thought to be related to
      various processes: cell division, movement of mitochondria and chloroplasts,
      cytoplasmic streaming, rearrangement of transvacuolar strands, and statolith
      positioning. Class VIII and XI myosins are represented in the Arabidopsis
      thaliana genome by 4 and 13 potential genes, respectively. The roles of
      individual class XI myosins and their cellular targets in A. thaliana are still
      unclear. In this work we implemented a reverse genetic approach to analyse the
      loss-of-function mutants of XIK, a representative of class XI myosins in A.
      thaliana. Three different T-DNA insertion mutants in the myosin XIK gene showed
      similar phenotypes: impaired growth of root hair cells, twisted shape of stem
      trichomes, and irregular size, branch positioning, and branch expansion of leaf
      trichomes. Morphometric analysis of mutant seedlings showed that the average
      length of root hairs was reduced up to 50% in comparison with wild-type root
      hairs, suggesting an involvement of the class XI myosin XIK in tip growth. On
      leaves, the proportion of trichomes with short branches was doubleed in mutant
      plants, and the mutant trichomes possessed a mildly twisted shape. Therefore, we
      concluded that myosin XIK is involved also in the elongation of stalks and
      branches of trichomes.

PMID- 17458635
TI  - Annexins: putative linkers in dynamic membrane-cytoskeleton interactions in plant
      cells.
AB  - The plasma membrane, the most external cellular structure, is at the forefront
      between the plant cell and its environment. Hence, it is naturally adapted to
      function in detection of external signals, their transduction throughout the
      cell, and finally, in cell reactions. Membrane lipids and the cytoskeleton, once
      regarded as simple and static structures, have recently been recognized as
      significant players in signal transduction. Proteins involved in signal detection
      and transduction are organised in specific domains at the plasma membrane. Their
      aggregation allows to bring together and orient the downstream and upstream
      members of signalling pathways. The cortical cytoskeleton provides a structural
      framework for rapid signal transduction from the cell periphery into the nucleus.
      It leads to intracellular reorganisation and wide-scale modulation of cellular
      metabolism which results in accumulation of newly synthesised proteins and/or
      secondary metabolites which, in turn, have to be distributed to the appropriate
      cell compartments. And again, in plant cells, the secretory vesicles that govern
      polar cellular transport are delivered to their target membranes by interaction
      with actin microfilaments. In search for factors that could govern subsequent
      steps of the cell response delineated above we focused on an evolutionary
      conserved protein family, the annexins, that bind in a calcium-dependent manner
      to membrane phospholipids. Annexins were proposed to regulate dynamic changes in
      membrane architecture and to organise the interface between secretory vesicles
      and the membrane. Certain proteins from this family were also identified as actin
      binding, making them ideal mediators in cell membrane and cytoskeleton
      interactions.

PMID- 17458636
TI  - Domain-specific mechanosensory transmission of osmotic and enzymatic cell wall
      disturbances to the actin cytoskeleton.
AB  - Plant protoplasts are embedded within surrounding cell walls and the cell wall
      plasma membrane-cytoskeleton (WMC) structural continuum seems to be crucial for
      the proper functioning of plant cells. We have utilised the protoplast
      preparation methodology to study the organisation and the putative components of
      the WMC continuum. Application of an osmotic agent evoked plasmolysis of the Zea
      mays root apex cells which appeared to be cell type- and growth stage-specific.
      Simultaneous use of wall polysaccharide-digesting enzymes selectively severed
      linkages between the components of the WMC continuum which changed the
      plasmolytic patterns in various cell types. This was followed by a reorganisation
      of filamentous actin aimed to reinforce protoplast boundaries and maintain the
      functioning of intercellular contact sites, especially at the cross walls.
      Particularly strong effects were evoked by pectin-degrading enzymes. Such
      treatments demonstrated directly the differentiated composition of various wall
      domains surrounding individual cells with the pectin-enriched cross walls
      (synapses), and the cellulose-hemicellulose network dominating the side walls.
      The same wall-degrading enzymes were used for in vitro digestion of isolated
      Lupinus albus cell walls followed by the extraction of wall proteins. Selective
      release of proteins suggested the importance of wall polysaccharide-protein
      interactions in the maintenance of the functioning and mechanical stability of
      root cell walls.

PMID- 17458638
TI  - Effects of nicardipine-induced hypotension on cerebrovascular carbon dioxide
      reactivity in patients with diabetes mellitus under sevoflurane anesthesia.
AB  - PURPOSE: The purpose of this study was to examine the effects of nicardipine
      induced hypotension on cerebrovascular CO2 reactivity in patients with diabetes
      mellitus under sevoflurane anesthesia. METHODS: Nineteen diabetic patients, and
      11 nondiabetic patients (serving as controls), undergoing elective orthopedic,
      cardiovascular, or thoracic surgery were included in the study. The diabetic
      patients were divided into three groups according to the antidiabetic therapy
      they were receiving, i.e., diet therapy (n = 6), oral antidiabetic drugs (n = 7),
      and insulin (n = 6). Anesthesia was maintained with 1.0 minimum alveolar
      concentration of sevoflurane. Absolute and relative cerebrovascular CO2
      reactivity was calculated using a 2.5-MHz pulsed transcranial Doppler (TCD) probe
      for the continuous measurement of mean blood flow velocity in the middle cerebral
      artery (Vmca). The cerebrovascular CO2 reactivity was measured both at baseline
      and during hypotension by increasing the ventilatory frequency by 4 to 7
      breaths.min(-1). Nicardipine was used to induce hypotension. RESULTS: We found
      that values for the Bispectral index (BSI), baseline mean blood pressure,
      endtidal CO2 (Pet(CO2)), and Vmca were essentially identical in all patients,
      irrespective of the type of antidiabetic treatment being taken. Values for
      absolute and relative CO2 reactivity in insulin-dependent patients, at both
      baseline blood pressure and during hypotension, were lower than those in patients
      in the antidiabetic drug, diet, and control groups (during hypotension, absolute
      CO2 reactivity: diet group: 3.2 +/- 0.9; oral antidiabetic drug group: 3.2 +/-
      0.7; insulin group: 1.5 +/- 0.6; control group: 3.4 +/- 0.8 cm.s(-1).mmHg(-1), [P
      < 0.05 insulin group vs the other groups]; relative CO2 reactivity: diet group,
      6.3 +/- 1.0; oral antidiabetic drug group, 6.5 +/- 0.8; insulin group, 3.5 +/-
      0.8; control group, 6.5 +/- 0.7%.mmHg(-1), [P < 0.05 insulin group vs the other
      groups]. CONCLUSION: We concluded that cerebrovascular CO2 reactivity in insulin
      dependent patients is impaired during nicardipine-induced hypotension under
      sevoflurane anesthesia.

PMID- 17458637
TI  - Cell-type-specific disruption and recovery of the cytoskeleton in Arabidopsis
      thaliana epidermal root cells upon heat shock stress.
AB  - The cytoskeleton in plant cells plays an important role in controlling cell shape
      and mediating intracellular signalling. However, almost nothing is known about
      the reactions of cytoskeletal elements to heat stress, which represents one of
      the major environmental challenges for plants. Here we show that living epidermal
      root cells of Arabidopsis thaliana could cope with short-term heat shock stress
      showing disruption and subsequent recovery of microtubules and actin
      microfilaments in a time-dependent manner. Time-lapse imaging revealed a very
      dynamic behavior of both cytoskeletal elements including transient
      depolymerization and disassembly upon heat shock (40-41 degrees C) followed by
      full recovery at room temperature (20 degrees C) within 1-3 h. Reaction of
      microtubules, but not actin filaments, to heat shock was dependent on cell type
      and developmental stage. On the other hand, recovery of actin filaments, but not
      microtubules, from heat shock stress was dependent on the same parameters. The
      relevance of this adaptive cytoskeletal behavior to intracellular signalling is
      discussed.

PMID- 17458639
TI  - Identification of independent predictors for intravenous thiopental-induced
      yawning.
AB  - PURPOSE: To explore risk factors for the yawning response induced by the
      intravenous administration of thiopental during the induction of general
      anesthesia. METHODS: We analyzed data from a cohort of 1322 patients who
      underwent elective surgery under general anesthesia plus intravenous thiopental.
      The data collected were: (a) the patients' demographic findings (age, sex,
      height, weight, cigarette smoking, hypertension, and presence of cerebral
      lesion), and (b) anesthesia-related findings (the kind of preanesthetic
      medication, i.e., atropine, epidural lidocaine, priming dose of vecuronium,
      fentanyl, and the dose of intravenous thiopental). An association between an
      individual variable in the evaluation model and the likelihood of thiopental
      induced yawning behavior was characterized by means of the odds ratio. Multiple
      logistic regression was used to examine the independent contribution of each
      candidate variable, while controlling for all variables. RESULTS: After the
      intravenous administration of thiopental, 461 patients exhibited a yawning
      response. The probability of this response was decreased by the prior use of
      intravenous fentanyl, by female sex, and by premedication with clonidine, but the
      probability was unaffected by premedication with hydroxyzine, by the prior use of
      atropine, or by the presence of hypertension or a cerebral lesion. CONCLUSION:
      Thiopental-induced yawning may be suppressed by female sex, prior use of
      intravenous fentanyl, and premedication with clonidine. These findings may allow
      insights into the physiologic and pharmacological aspects of yawning in humans,
      thereby leading to the development methods to prevent thiopental-induced yawning.

PMID- 17458640
TI  - Factors influencing intraoperative bradycardia in adult patients.
AB  - PURPOSE: In order to elucidate the prominent factors involved in intraoperative
      bradycardia in adult patients, we retrospectively investigated the association
      between the potential risk factors and intraoperative bradycardia, using multiple
      logistic regression. METHODS: The perioperative records for 499 adult patients
      who had undergone any of six elective surgeries were retrospectively examined.
      The potential factors included patient characteristics, the use of perioperative
      drugs for anesthesia, and the types of operational procedures. Heart rates were
      extracted at five points perioperatively. The frequencies and total doses of
      atropine injections to treat bradycardia were examined. Simple and multiple
      logistic regressions were used to analyze the relative risk factors for a
      intraoperative bradycardia. RESULTS: The multiple logistic regression analysis
      revealed that the absence of atropine premedication was the most prominent risk
      factor for bradycardia (odds ratio; 1.86-5.51) from arrival in the operating room
      until the end of the operation. Other prominent factors, whose effects were only
      temporary, were as follows. Males had a higher risk of bradycardia than females
      upon arrival in the operating room. Surgical procedures with an epidural or
      subarachnoid blockade tended to have a higher risk for bradycardia after the
      operation. Propofol induction had a greater risk for bradycardia than thiopental
      after the end of the operation. Endotracheal intubation had a lower risk for
      bradycardia than no endotracheal intubation after induction. Vecuronium tended to
      induce bradycardia after operation. CONCLUSION: The most prominent factor
      affecting heart rate was atropine premedication. It was noteworthy that a single
      preoperative administration of atropine affected heart rate throughout the
      operation.

PMID- 17458641
TI  - Epidural clonidine added to a bupivacaine infusion increases analgesic duration
      in labor without adverse maternal or fetal effects.
AB  - PURPOSE: Many obstetric patients receiving epidural analgesia are encouraged to
      ambulate. This current study was designed to determine the potential for
      maximizing the time to first epidural supplement when adding clonidine to a 0.625
      mg.ml(-1) bupivacaine continuous epidural infusion following epidural fentanyl
      bolus in early labor for patients allowed to ambulate. Maternal and fetal effects
      secondary to clonidine were also evaluated. METHODS: Sixty-eight laboring
      primigravid women received a 3-ml epidural test dose of lidocaine with
      epinephrine, followed by a fentanyl 100-microg bolus (in a 10 ml-volume). The
      patients then received a 0.625 mg.ml(-1) bupivacaine continuous epidural
      infusion, either with or without clonidine (5 microg.ml(-1)), at a rate of 10
      ml.h(-1). Pain scores and side effects were recorded for each patient. RESULTS:
      The overall quality of analgesia was similar in both groups. The mean duration
      prior to request for additional analgesia was significantly longer in the
      clonidine group (269 +/- 160 min), compared to the control group (164 +/- 64
      min). No patient in either group experienced any detectable motor block; one
      patient (clonidine group) complained of mild thigh numbness and was not allowed
      to ambulate. While mean blood pressure was approximately 6 mmHg lower in the
      clonidine group at 1, 1.5, and 3.5 h, this was not clinically significant. No
      adverse effects on maternal heart rate or fetal heart rate were noted.
      CONCLUSION: In early laboring patients, addition of clonidine prolongs the
      analgesia duration of a 0.625 mg.ml(-1) bupivacaine continuous epidural infusion
      following 100 microg epidural fentanyl (after a lidocaine-epinephrine test dose)
      without a clinically significant increase in side effects.

PMID- 17458642
TI  - Impact of Sonoclot hemostasis analysis after cardiopulmonary bypass on
      postoperative hemorrhage in cardiac surgery.
AB  - PURPOSE: The Sonoclot Analyzer provides a functional test of whole blood
      coagulation by measuring the viscous property of the blood sample. In this study,
      we used a modified Sonoclot assay, using cuvettes with a glass bead activator
      containing heparinase, and compared the Sonoclot data before and after
      cardiopulmonary bypass (CPB) to assess the usefulness in predicting postoperative
      hemorrhage. METHODS: In 41 cardiac surgery patients, Sonoclot data were obtained
      immediately after heparin administration (pre-bypass) and just before protamine
      administration (post-bypass). Excessive bleeding was defined as chest tube
      drainage greater than 2 ml.kg(-1).h(-1) in 1 h during the first 4 h after
      surgery. RESULTS: There were no significant differences in Sonoclot values before
      and after CPB in patients with acceptable bleeding (n = 29). In patients with
      excessive bleeding (n = 12), Sonoclot variables reflecting fibrin formation
      (activated clotting time [ACT], rate of fibrin formation [clot rate], and peak
      clot signal) were preserved after CPB; however, the variables reflecting platelet
      fibrin interaction (time to peak, peak angle, and clot retraction rate) were
      significantly different from their respective pre-bypass values. Sonoclot
      analysis showed impairment of clot maturation after CPB in patients with
      excessive postoperative bleeding. CONCLUSION: Our results suggest that abnormal
      postoperative hemorrhage can be predicted by Sonoclot analysis with a new glass
      bead-activated heparinase test performed after CPB.

PMID- 17458643
TI  - Correlation between precise and simple tests in recovery of dynamic balance
      function after intravenous sedation with midazolam in the elderly.
AB  - PURPOSE: Assessing the recovery of dynamic balance after intravenous sedation in
      the elderly is important for ensuring their safe discharge, especially when they
      are walking. A reliable, simple dynamic balance test would be useful in daily
      clinical practice. We observed the recovery of balance after intravenous sedation
      with midazolam, using computerized dynamic posturography (CDP), and we evaluated
      the correlation between the CDP result and the results of simple dynamic balance
      tests. METHODS: Midazolam was administered in divided doses, until the Wilson
      sedation score reached 3, in 18 elderly male volunteers. The dynamic balance test
      using CDP with perturbation stimuli was performed before and after sedation. As
      simple dynamic balance tests, the usual-speed walking (USW) and maximum-speed
      walking (MSW) tests and a modified timed "up and go" (TUG) test (subjects stand
      up from a chair, walk 5 m forward and return to the chair with MSW, and sit down
      again) were performed. RESULTS: The recovery times (defined as the time until the
      significant difference between the value at each time point and the baseline
      value disappeared) in the dynamic balance test (CDP), USW test, MSW test, and TUG
      test, were 80, 40, 80, 80 min, respectively. There was a significant, strong
      positive correlation between the result of the dynamic balance test (CDP) and the
      TUG test (P < 0.01; r = 0.70). CONCLUSION: The TUG test is a useful simple
      dynamic balance/motor test that can be used in daily clinical practice in the
      elderly.

PMID- 17458644
TI  - Lornoxicam and ondansetron for the prevention of intrathecal fentanyl-induced
      pruritus.
AB  - PURPOSE: In this randomized, double-blind study, we aimed to compare the
      effectiveness of lornoxicam and ondansetron for the prevention of intrathecal
      fentanyl-induced pruritus in patients undergoing cesarean section. METHODS: One
      hundred and eight parturients (American Society of Anesthesiologists [ASA] I-II
      status) requesting neuraxial analgesia by a combined spinal-epidural (CSE)
      technique were recruited for this study. A CSE technique was performed and
      anesthesia was achieved with fentanyl 25 microg and hyperbaric bupivacaine 12 mg.
      Patients were randomly allocated to three groups, each with 36 participants.
      Immediately following delivery, patients received either lornoxicam 8 mg IV
      (group L; n = 36), ondansetron 8 mg IV (group O; n = 36), or normal saline 2 ml
      IV (group P; n = 36). Pruritus, pain, and nausea and vomiting scores were
      recorded during the initial 24 h postoperatively. RESULTS: The incidence of
      pruritus was significantly lower in group O from 4 to 12 h postoperatively when
      compared to that in group L and group P. According to the pruritus grading system
      we used, the number of patients without pruritus was significantly higher in
      group O when compared to that in group L and group P. The number of patients
      experiencing moderate pruritus was significantly lower in group O when compared
      to that in group P. CONCLUSION: We observed that the administration of 8 mg IV
      lornoxicam failed to prevent intrathecal fentanyl-induced pruritus in
      parturients. Also, our data confirmed that ondansetron is likely to attenuate
      intrathecal fentanyl-induced pruritus.

PMID- 17458645
TI  - Nafamostat mesilate inhibits the expression of HMGB1 in lipopolysaccharide
      induced acute lung injury.
AB  - PURPOSE: High mobility group box 1 (HMGB1) protein has recently been shown to be
      an important late mediator of acute lung injury and a promising therapeutic
      target. Nafamostat mesilate (NM) is a broad-range synthetic protease inhibitor
      with some anti-inflammatory action. The purpose of this study was to evaluate the
      effect of NM on HMGB1 in lipopolysaccharide (LPS)-induced lung injury in rats.
      METHODS: Male Wistar rats were given either saline (LPS group) or NM (NM+LPS
      group) 30 min before the intravenous injection of a bolus of LPS (5 mg.kg(-1)).
      After the administration of LPS, injury to the lung and the expression of HMGB1,
      tumor necrosis factor-alpha (TNF-alpha), and plasminogen activator inhibitor-1
      (PAI-1) were examined. RESULTS: Histological examination revealed that
      interstitial edema, leukocytic infiltration, and HMGB1 protein expression were
      markedly reduced in the NM+LPS group compared to the LPS group. Furthermore, the
      LPS-induced increases in PAI-1 activity and in plasma TNF-alpha concentrations
      were also lower in the rats given both NM and LPS than in the rats given LPS
      alone. CONCLUSIONS: The anticoagulatory activity of NM may have inhibited PAI-1,
      while its anti-inflammatory activity blockaded TNF-alpha, thereby indirectly
      inhibiting HMGB1 and reducing tissue damage in the lung. These findings indicate
      that NM can inhibit the lung injury induced by LPS in rats. NM is an excellent
      candidate for use in new therapeutic strategies to prevent or minimize lung
      injury.

PMID- 17458646
TI  - Succinylcholine potentiates acetylcholine-induced contractile and
      phosphatidylinositol responses of rat trachea.
AB  - PURPOSE: Although succinylcholine (SCh) is often used as a muscle relaxant in
      electroconvulsive therapy, its influence on airway reactivity has not been fully
      investigated. We examined the effects of SCh on acetylcholine (ACh)-, carbachol
      (CCh)-, and electrical field stimulation (EFS)-induced contractions, and on the
      ACh-induced phosphatidylinositol (PI) response of rat trachea. METHODS: Thirty
      two male Wistar rats weighing 250-350 g were used. The trachea was rapidly
      isolated and cut into 3-mm-wide rings. The resting tension was adjusted
      periodically to 1.0 g during the equilibration period. ACh, 1 microM; carbachol
      (CCh), 0.05 microM; or neither of them, was added, and SCh was then added at 1
      300 microM final concentrations, and ring tension was examined. Contractions were
      elicited by EFS in the presence or absence of 100 microM SCh. Tracheal slices
      were incubated with [3H] myo-inositol, 1 microM ACh, and various concentrations
      of SCh. The accumulation of [3H] inositol monophosphate (IP1) was measured.
      RESULTS: SCh did not affect the tension by itself without ACh, or with CCh, but
      SCh potentiated the ACh-induced contraction of rat trachea at concentrations of
      10 microM or more (50% effective concentration [EC50]; 43.6 microM). SCh produced
      a significant increase in the amplitude and duration of EFS-induced contractions.
      SCh, at concentrations of 10 microM and 100 microM, potentiated ACh-induced IP1
      accumulation. CONCLUSION: SCh potentiated ACh-induced, but not CCh-induced,
      contractile and PI responses, and enhanced EFS-induced contraction of rat
      trachea, suggesting that competition for butyrylcholinesterase (BChE) in airway
      smooth muscle could be involved in the potentiation by SCh of ACh-induced airway
      smooth muscle contraction.

PMID- 17458647
TI  - Cardioprotection induced by olprinone, a phosphodiesterase III inhibitor,
      involves phosphatidylinositol-3-OH kinase-Akt and a mitochondrial permeability
      transition pore during early reperfusion.
AB  - PURPOSE: Ischemic preconditioning is mediated by the activation of
      phosphatidylinositol-3-OH kinase-Akt (PI3K-Akt) and by the inhibition of the
      opening of a mitochondrial permeability transition pore (mPTP) during early
      reperfusion. Preischemic administration of the phosphodiesterase type III
      inhibitor olprinone protects the myocardium against infarction, but its mechanism
      has not been fully clarified. We hypothesized that this olprinone-induced
      cardioprotective effect was mediated by the activation of PI3K-Akt and by the
      inhibition of mPTP during early reperfusion. METHODS: Pentobarbital-anesthetized
      rats (n = 42) subjected to 30-min coronary occlusion followed by 2-h reperfusion,
      received olprinone (20 microg.kg(-1)) or saline (control) in the preischemic
      phase in the presence or absence of the PI3K-Akt inhibitor wortmannin (0.6 mg.kg(
      1)) or the mPTP opener atractyloside (5 mg.kg(-1)) before 5 min of reperfusion.
      The myocardial infarct size was expressed as a percentage of the area at risk.
      All values were expressed as means +/- SD. Statistical comparisons within groups
      were made using repeated-measures analysis of variance (ANOVA), followed by a
      paired t-test, and comparisons among groups were analyzed using a two-way ANOVA,
      followed by the Tukey-Kramer test. RESULTS: Mean arterial pressure and heart rate
      showed no significant differences within or among groups. The preischemic
      administration of olprinone significantly reduced the infarct size (12 +/- 4%) as
      compared with that in the control group (43 +/- 4%). Wortmannin or atractyloside
      abolished the protective effect of olprinone (42 +/- 11% or 41 +/- 10%).
      CONCLUSION: The olprinone-induced cardioprotective effect could be exerted via
      the activation of PI3K-Akt and the inhibition of mPTP during early reperfusion.

PMID- 17458648
TI  - Cardiac output increases the rate of carbon monoxide elimination in hyperpneic
      but not normally ventilated dogs.
AB  - PURPOSE: The very high solubility of carbon monoxide (CO) in blood suggests that
      its elimination depends predominantly on ventilation and not perfusion.
      Nevertheless, hyperventilation is not used for CO elimination because of the
      adverse effects of hypocapnia. With isocapnic hyperpnea (IH), ventilation can be
      increased considerably without hypocapnia. This raises the issue of whether CO
      elimination is limited by perfusion during IH. We studied the effect of
      increasing cardiac output on t1/2, the half-time of decline of blood
      carboxyhemoglobin concentration ([COHb]), during normal ventilation (NV) and
      during IH. METHODS: After ethics approval was received, 13 pentobarbital
      anesthetized ventilated dogs were exposed to CO to increase their [COHb]. They
      were then ventilated with NV or IH. At each level of ventilation, dogs were
      randomly assigned to treatment with dobutamine (to increase cardiac output) or to
      no dobutamine treatment. After the return of [COHb] to control levels, each dog
      was re-exposed to CO and treated with the same ventilatory mode, but the
      alternative inotropic treatment. RESULTS: Gas exchange, [COHb], and hemodynamic
      measures were recorded during the study. Cardiac index values in the IH group
      were 4.1 +/- 0.5 and 8.2 +/- 1.2 l.min(-1).m(-2) without and with dobutamine
      infusion, respectively. Dobutamine infusion was associated with a reduction in
      t1/2 from 20.3 +/- 3.6 to 16.9 +/- 2.4 min (P = 0.005) in the IH group, but no
      change in the NV group. CONCLUSION: These findings suggest that CO elimination
      during IH treatment is limited at least partly by pulmonary blood flow and may
      therefore be further augmented by increasing cardiac output.

PMID- 17458649
TI  - Mechanisms of anesthetic actions and the brain.
AB  - The neural mechanisms behind anesthetic-induced behavioral changes such as loss
      of consciousness, amnesia, and analgesia, are insufficiently understood, though
      general anesthesia has been of tremendous importance for the development of
      medicine. In this review, I summarize what is currently known about general
      anesthetic actions at different organizational levels and discuss current and
      future research, using systems neuroscience approaches such as functional
      neuroimaging and quantitative electrophysiology to understand anesthesia actions
      at the integrated brain level.

PMID- 17458651
TI  - Volatile anesthetic-induced cardiac preconditioning.
AB  - Pharmacological preconditioning with volatile anesthetics, or anesthetic-induced
      preconditioning (APC), is a phenomenon whereby a brief exposure to volatile
      anesthetic agents protects the heart from the potentially fatal consequences of a
      subsequent prolonged period of myocardial ischemia and reperfusion. Although not
      completely elucidated, the cellular and molecular mechanisms of APC appear to
      mimic those of ischemic preconditioning, the most powerful endogenous
      cardioprotective mechanism. This article reviews recently accumulated evidence
      underscoring the importance of mitochondria, reactive oxygen species, and K(ATP)
      channels in cardioprotective signaling by volatile anesthetics. Moreover, the
      article addresses current concepts and controversies regarding the specific roles
      of the mitochondrial and the sarcolemmal K(ATP) channels in APC.

PMID- 17458650
TI  - Tobacco control for anesthesiologists.
AB  - Anesthesiologists daily witness the consequences of tobacco use, the most common
      preventable cause of death. Smoking-related diseases such as atherosclerosis and
      chronic obstructive pulmonary disease increase anesthetic risk, and even smokers
      without overt disease are at increased risk for morbidity such as pulmonary and
      wound-related complications. Evidence suggests that stopping smoking will reduce
      the frequency of these complications. Nicotine and the other constituents of
      cigarette smoke, such as carbon monoxide, have important physiologic effects that
      may affect perioperative management. In addition, it is now apparent that the
      scheduling of elective surgery represents an excellent opportunity for smokers to
      quit in the long term. This review serves as an introduction to tobacco control
      for anesthesiologists, first examining issues of importance to perioperative
      management. It then discusses how anesthesiologists and other perioperative
      physicians can help address tobacco use, both at an individual level with their
      patients, and by contributing to the implementation of effective public health
      strategies in their countries. Anesthesiologists can play a key role in helping
      their patients quit smoking. Effective tobacco control measures applied to
      surgical patients will not only improve immediate perioperative outcomes but also
      long-term health.

PMID- 17458654
TI  - Advances in obstetric anesthesia: anesthesia for fetal intrapartum operations on
      placental support.
AB  - Fetal intrapartum operations on placental support (OOPS), also known as ex-utero
      intrapartum treatment (EXIT) procedures, are very rare (and often challenging)
      surgical techniques designed to allow partial delivery (cesarean section) of a
      fetus with a potentially difficult airway, with subsequent management of the
      neonatal airway (direct laryngoscopy, fiberoptic bronchoscopy, or tracheostomy)
      while oxygenation is continuously maintained via the placenta (on placental
      support). The peripartum management of pregnant women and their fetuses
      undergoing OOPS is very complex and multidisciplinary, and differs greatly from
      that of standard cesarean sections. The goal of this article is to review the
      current recommendations for the peripartum anesthetic management of pregnant
      women carrying fetuses with fetal congenital malformations undergoing OOPS.

PMID- 17458652
TI  - Cellular and molecular mechanisms regulating vascular tone. Part 1: basic
      mechanisms controlling cytosolic Ca2+ concentration and the Ca2+-dependent
      regulation of vascular tone.
AB  - General anesthetics cause hemodynamic instability and alter blood flow to various
      organs. There is mounting evidence that most general anesthetics, at clinical
      concentrations, influence a wide variety of cellular and molecular mechanisms
      regulating the contractile state of vascular smooth muscle cells (i.e., vascular
      tone). In addition, in current anesthetic practice, various types of vasoactive
      agents are often used to control vascular reactivity and to sustain tissue blood
      flow in high-risk surgical patients with impaired vital organ function and/or
      hemodynamic instability. Understanding the physiological mechanisms involved in
      the regulation of vascular tone thus would be beneficial for anesthesiologists.
      This review, in two parts, provides an overview of current knowledge about the
      cellular and molecular mechanisms regulating vascular tone-i.e., targets for
      general anesthetics, as well as for vasoactive drugs that are used in
      intraoperative circulatory management. This first part of the two-part review
      focuses on basic mechanisms regulating cytosolic Ca2+ concentration and the Ca2+
      dependent regulation of vascular tone.

PMID- 17458655
TI  - Anesthesia for pregnant women with valvular heart disease: the state-of-the-art.
AB  - Pregnancy results in dramatic changes in the cardiovascular system. Maternal
      heart disease complicates 0.2%-3% of pregnancies. Valvular heart disease in women
      of reproductive age is most commonly due to rheumatic heart disease,
      endocarditis, or congenital abnormalities. In general, regurgitant lesions are
      well tolerated during pregnancy because the increased plasma volume and lowered
      systemic vascular resistance result in increased cardiac output. In contrast,
      stenotic valvular disease is poorly tolerated with advancing pregnancy, owing to
      the inability to increase cardiac output in relation to the increased plasma
      volume preload. The choice of anesthesia depends on the lesion and its severity.
      Usually, regional anesthesia provides the least amount of alteration in
      hemodynamics, although general anesthesia for cesarean section can be equally
      safe when the abrupt changes associated with laryngoscopy, intubation, and
      extubation are blunted by the appropriate choice of pharmacological agents and
      anesthetic techniques.

PMID- 17458653
TI  - Cellular and molecular mechanisms regulating vascular tone. Part 2: regulatory
      mechanisms modulating Ca2+ mobilization and/or myofilament Ca2+ sensitivity in
      vascular smooth muscle cells.
AB  - Understanding the physiological mechanisms regulating vascular tone would lead to
      better circulatory management during general anesthesia. This two-part review
      provides an overview of current knowledge about the cellular and molecular
      mechanisms regulating the contractile state of vascular smooth muscle cells
      (i.e., vascular tone). The first part reviews basic mechanisms controlling the
      cytosolic Ca2+ concentration in vascular smooth muscle cells, and the Ca2+
      dependent regulation of vascular tone. This second part reviews the regulatory
      mechanisms modulating Ca2+ mobilization and/or myofilament Ca2+ sensitivity in
      vascular smooth muscle cells-including Rho/Rho kinase, protein kinase C,
      arachidonic acid, Ca2+/calmodulin-dependent protein kinase II, caldesmon,
      calponin, mitogen-activated protein kinases, tyrosine kinases, cyclic
      nucleotides, Cl- channels, and K+ channels.

PMID- 17458656
TI  - Postoperative pulmonary thromboembolism possibly associated with recombinant
      activated factor VII infusion for the treatment of uncontrolled hemorrhage during
      vertebral instrumentation.
AB  - We report the successful use of recombinant activated factor VII (rFVIIa)
      infusion in an 18-year-old man who underwent L3 laminectomy and pedicular screw
      fixation with severe refractory bleeding secondary to severe coagulopathy, which
      had remained unresponsive to conventional medical and surgical therapies.
      However, the patient developed a thromboembolic complication presumably
      associated with the use of rFVIIa. Although rFVIIa provides a dramatic response
      in intractable bleeding, it may cause a thromboembolic phenomenon which should be
      vigilantly considered and promptly treated.

PMID- 17458657
TI  - Anesthetic management of an extremely obese patient.
AB  - We present the case of a morbidly obese woman, with a body mass index (BMI) of
      73.7 kg.m(-2), who had a gynecological operation under combined general and
      epidural anesthesia. The patient's trachea was intubated, using a fiberscope,
      while she was breathing spontaneously after the intravenous injection of fentanyl
      and propofol as sedatives. Anesthesia was maintained with intravenous propofol
      and epidural mepivacaine. When the gynecologist placed a sponge in the abdominal
      cavity to retract the bowel, the patient experienced severe arterial
      deoxygenation and mild hypotension, due to massive atelectasis of the left lung.
      Both oxygenation and perfusion were corrected by the removal of the sponge and
      with the placement of a pillow under the patient's left shoulder. The atelectasis
      resulted from compression of the left lung by the fatty mediastinum and by the
      diaphragm being pushed up by the sponge. The hypotension resulted from impaired
      venous return and hypoxia. The patient suffered no perioperative complications
      other than atelectasis and a surgical-site infection. Key factors that
      contributed to the favorable outcome of this patient included a careful tracheal
      intubation technique, the choice and dose of anesthetic agents, immediate
      correction of the factors leading to atelectasis, early ambulation, and
      prophylaxis for deep vein thrombosis.

PMID- 17458658
TI  - Propofol infusion for sedation during spinal anesthesia.
AB  - PURPOSE: The dose and time course of propofol infusion required to induce rapid
      sedation without oversedation during spinal anesthesia were investigated.
      METHODS: Forty patients scheduled for spinal and epidural anesthesia were
      studied. After premedication with intramuscular midazolam 0.04 mg.kg(-1), an
      epidural catheter was inserted, followed by spinal anersthesia at L4-L5 with 0.5%
      hyperbaric tetracaine with epinephrine. The infusion of propofol was started with
      10 mg.kg(-1).h(-1) and was decreased to 5 mg.kg(-1).h(-1) at spontaneous eye
      closure. According to the increase or decrease of the sedation level, the
      infusion does was decreased or increased to half or twice the initial dose,
      respectively, to keep the Observer's Assessment of Alertness Sedation (OAAS)
      score at 3 or 4. RESULTS: Eye closure was observed at 1.0 +/- 0.4 min after the
      start of insusion. The maintenance insusion dose to keep the OAAS score at 3 or 4
      was about 2.5 mg.kg(-1).h(-1). CONCLUSION: Propofol infusion, starting with 10
      mg.kg(-1).h(-1), decreasing to 5 mg.kg(-1).h(-1) after 1 minute, and then
      decreasing to 2.5 mg.kg(-1).h(-1) after another min induced rapid onset of
      sedation and kept the OAAS score at 3 or 4 during spinal anesthesia.

PMID- 17458659
TI  - Tethered cord syndrome discovered in preoperative examination.
AB  - We present an instructive case of a 47-year-old female patient with tethered cord
      syndrome, discovered before arthroscopy was to be performed under routine spinal
      anesthesia for right knee arthritis. The patient had no symptoms except for right
      knee-joint pain, but weakness in the left dorsiflexors and decreased range of
      motion in the left ankle and toe joints were found on preoperative physical
      examination. In addition, clawfoot deformity was discovered in the left foot. A
      small stigma was observed on the skin in the sacral region. A magnetic resonance
      imaging scan showed the spinal cord tethered to an intrathecal mass in the sacral
      region. Therefore, we avoided spinal anesthesia. The arthroscopy proceeded
      uneventfully with the patient under general anesthesia.

PMID- 17458660
TI  - Circulatory collapse caused by unnoticed hypermagnesemia in a hospitalized
      patient.
AB  - We report a case of hypermagnesemia in a hospitalized patient after prolonged
      laxative use; due to preexisting impaired consciousness and digestive problems,
      the hypermagnesemia was difficult to detect until it almost became fatal. A 64
      year-old man who was a patient at another hospital for treatment of head injury
      and gastric ulcer had developed circulatory collapse and was transferred to our
      hospital. Hypermagnesemia (serum magnesium concentration 11.0 mg.dl(-1)) was
      thought to be the cause of the circulatory collapse and treatments were
      successful. A magnesium laxative had been administered for more than a month at
      the previous hospital, but the patient's serum magnesium level was never
      measured. Care should be taken when a magnesium laxative is administered to
      patients who already have impaired consciousness and digestive problems that are
      early symptoms of hypermagnesemia.

PMID- 17458661
TI  - Clinical outcome of percutaneous osteoplasty for pain caused by metastatic bone
      tumors in the pelvis and femur.
AB  - We examined the pain-relieving effects in five patients who underwent
      percutaneous osteoplasty (POP) for pain caused by metastatic bone tumors in the
      pelvis and femur. Pain intensity, improvement of walking, and complications
      associated with POP were evaluated. Pain was measured using a numerical rating
      scale (NRS), with scores ranging from 0 (no pain) to 10 (worst pain imaginable).
      The patients were four men and one woman (mean age, 65 years). POP was performed
      in the pelvis in three patients and in the femur in two patients. Three of the
      subjects had already received radiation therapy at the lesion. The scores on the
      NRS on moving in the five patients before POP were 5, 8, 5, 4, and 7. After POP,
      the NRS scores decreased to 0, 0, 2, 0, and 1, respectively, within 72 hs. Three
      of the patients showed improvements in walking. There were no complications
      associated with POP. However, pathological fracture occurred, while walking, 4
      days after POP in one patient. Percutaneous osteoplasty is a safe and effective
      treatment for pain caused by metastatic bone tumors in the pelvis and femur.
      However, care and attention should be paid to the risk of pathological fracture
      after POP of the femur.

PMID- 17458662
TI  - Recovery from Fontan circulation failure by application of continuous negative
      extrathoracic pressure.
AB  - A 2-year-old girl developed lethal circulatory failure, general edema, and
      hepatic dysfunction in an acute phase after total cavopulmonary connection, a
      Fontan-type operation. Application of continuous negative extrathoracic pressure
      (CNEP) with a cuirass ventilator at -4 cmH2O under spontaneous respiration
      dramatically improved hemodynamics, with systolic arterial pressure increasing
      from 82 mmHg to 90 mmHg, and central venous pressure decreasing from 15 mmHg to
      13 mmHg; also, urine output increased, from 1.6 ml.kg(-1).h(-1) to 6.4 ml.kg(
      1).h(-1). Improvements in hepatic function and fluid retention (reduction of
      pleural fluid and ascites) were also observed. The patient was successfully
      weaned from CNEP after 5 days. CNEP is an easily applicable, noninvasive tool to
      reduce pulmonary impedance, and is specifically useful to improve hemodynamics in
      patients after a Fontan-type operation. Our result suggests that CNEP may
      represent a first-line option to save patients from critical circulatory failure
      after a Fontan-type operation.

PMID- 17458663
TI  - Fulminant-type malignant hyperthermia in Japan: cumulative analysis of 383 cases.
AB  - We investigated the transition of clinical signs of fulminant-type malignant
      hyperthermia (f-MH) by analyzing a database consisting of 383 cumulative cases of
      f-MH from 1961 to 2004. The cases were divided by time period into group 1 (1961
      1984), group 2 (1985-1994), and group 3 (1995-2004). The variables considered
      were age, sex, type of agents used (succinylcholine and volatile anesthetics),
      dantrolene administration, clinical signs, laboratory data, and mortality. The
      level of statistical significance was considered to be less than 5%. Groups 1, 2,
      and 3 consisted of 196, 127, and 60 cases, respectively. In groups 1, 2, and 3,
      the rates of dantrolene administration were 18.4%, 93.6%, and 86.7%; the rates of
      occurrence of ventricular arrhythmia were: 75.2%, 55.6%, and 35.0%; and the rates
      of generalized muscle rigidity were 64.7%, 60.9%, and 23.9%, respectively. The
      mortality rate decreased over time, from 42.3% in group 1, to 15.0% in group 2
      and group 3. We considered that this decrease occurred because of the increased
      use of dantrolene and the early diagnosis of malignant hyperthermia in the latter
      two groups.

PMID- 17458665
TI  - Kinking of a tube in the pharynx.

PMID- 17458666
TI  - The angle of needle insertion during internal jugular vein cannulation.

PMID- 17458667
TI  - Increased airway resistance in the prone position associated with heat and
      moisture exchangers with integral bacterial/viral filters.

PMID- 17458668
TI  - Lumbar tattoos, magnetic resonance imaging, and obstetric anesthesia: what do
      they have in common?

PMID- 17458669
TI  - Preemptive analgesia by preoperative administration of nonsteroidal anti
      inflammatory drugs.

PMID- 17458670
TI  - Application of the Truview EV02 optical laryngoscope to patients with cervical
      spinal disease.

PMID- 17458672
TI  - Molecular epidemiology of uropathogenic Escherichia coli.
AB  - Escherichia coli is the most common cause of complicated as well as uncomplicated
      urinary tract infections (UTIs). Most of these uropathogenic E. coli (UPEC)
      strains exhibit certain virulence factors (VFs), including adhesins, iron uptake
      systems, synthesis of cytotoxins, and specific O:K:H serotypes. Molecular
      epidemiological studies of UPEC have contributed to the discovery of
      uropathogenic VFs, to an understanding of the pathogenesis of UTIs as ascending
      infections, and to the clarification of genetic linkages between different
      virulence genes such as pathogenicity islands (PAIs), which are one of the
      mechanisms for horizontal VF gene transfers between the same or related species.
      Uropathogenic VFs not only play an important role individually but also work
      cooperatively in a fine-tuned manner with coordinated regulation and expression.

PMID- 17458673
TI  - Trends in the gentamicin and arbekacin susceptibility of methicillin-resistant
      Staphylococcus aureus and the genes encoding aminoglycoside-modifying enzymes.
AB  - It is generally accepted that methicillin-resistant Staphylococcus aureus (MRSA)
      is also resistant to aminoglycoside antibiotics. We investigated trends of
      gentamicin and arbekacin susceptibilities and the prevalence of the genes
      encoding aminoglycoside-modifying enzymes (AMEs) for a total of 218 strains of
      MRSA isolated from blood specimens obtained from 1978 through 2002 in one
      hospital. The minimum inhibitory concentrations of gentamicin at which 50% of the
      strains were inhibited (MIC(50)) were > or =128 and 32 microg/ml for isolates
      obtained from 1978 to 1984 and from 1985 to 1989, respectively, and 0.5 microg/ml
      for isolates obtained from 1990 to 2002. The MIC(90) of gentamicin was
      consistently > or =128 microg/ml. Investigation of the occurrence of AME revealed
      that the MIC(50) of gentamicin was highly correlated with the presence of
      aac(6')/aph(2'') encoding aminoglycoside acetyl/phosphotransferase. The MIC(50)
      of arbekacin was 2 microg/ml for strains isolated in 1978-1984 and </=0.5
      microg/ml for strains isolated from 1985 to 2002. The MIC(90) of arbekacin was 8
      microg/ml for the strains isolated in 1978-1989 and 1 to 2 microg/ml for strains
      isolated in 1990-2002. Though it has been established that AAC(6')/APH(2'')
      modifies arbekacin, the trend of arbekacin resistance was not necessarily
      consistent with the presence of this enzyme. However, the prevalence of both
      aac(6')/aph(2'') and aph(3')-III in the strains isolated from 1978 through 2002
      was correlated with the MIC(90) values of arbekacin. Thus, it is most likely that
      APH(3')-III, in addition to AAC(6')/APH(2''), is somehow involved in arbekacin
      resistance in S. aureus. Our results imply that gentamicin- and arbekacin
      resistant MRSAs have consistently decreased for the past 25 years and that this
      finding is, most likely, attributable to the declining prevalence of genes
      encoding for AMEs.

PMID- 17458674
TI  - Characterization of oxacillin-susceptible mecA-positive Staphylococcus aureus: a
      new type of MRSA.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has been defined as S. aureus
      having the mecA gene or showing a minimum inhibitory concentration (MIC) of
      oxacillin higher than 4 mg/l. However, some clinical isolates are mecA-positive
      and oxacillin-susceptible. Therefore, we surveyed the occurrence of S. aureus
      having the mecA gene and an MIC of oxacillin of less than 2 mg/l (oxacillin
      susceptible MRSA; OS-MRSA) in a total of 480 strains of S. aureus collected from
      11 hospitals in different location in Japan isolated from 2003 through 2005. We
      found 6 strains matching the criteria for OS-MRSA. All 6 strains were
      staphylococcal cassette chromosome (SCC) mec-positive, without exception, and 4
      strains showed the SCCmec type III-variant, which is unique in Japan. These OS
      MRSAs were least resistant to oxacillin among the MRSAs tested and they were
      within the susceptible range to seven other beta-lactam antibiotics tested. Thus,
      OS-MRSA may become a high-resistant MRSA upon the treatment of patients with beta
      lactam antibiotics. To characterize whether these OS-MRSAs were hospital-acquired
      or community-acquired MRSAs, we tested for the presence of the genes encoding
      toxins. Genes encoding hemolysin, exfoliative toxin, enterotoxin, toxic shock
      syndrome toxin-1, and Panton-Valentine leukocidin were found in 6, 4, 0, 0, and 0
      strains, respectively. These results revealed that OS-MRSAs could be classified
      as a new type of MRSA that exhibits properties distinguishable from either
      hospital- or community-acquired MRSA. Coagulase typing of the OS-MRSAs supported
      the above conclusion. In this study, the occurrence of OS-MRSA at a certain
      frequency was noted; precautions are called for in the classification of
      oxacillin-resistant S. aureus and in the treatment of OS-MRSA infection.

PMID- 17458675
TI  - A comparative in vitro photoinactivation study of clinical isolates of multidrug
      resistant pathogens.
AB  - Photodynamic inactivation (PDI) has been investigated to cope with the increasing
      incidence of multidrug-resistant (MDR) pathogens. In Hong Kong, methicillin
      resistant Staphylococcus aureus (MRSA) and extended-spectrum beta-lactamase
      (ESBL)-producing Escherichia coli are the two commonest MDR pathogens. Here, we
      studied the photodynamic inactivation (PDI) mediated by poly-L-lysine chlorin(e6)
      conjugate (pL-ce6) and toluidine blue O (TBO) in clinical MRSA and ESBL producing
      E. coli, together with their corresponding American Type Culture Collection
      (ATCC) strains. Both pL-ce6 and TBO mediated a light- and drug dose-dependent
      efficacy for the four pathogens. pL-ce6 was more effective. pL-ce6 at 8 microM,
      30 Jcm(-2), attained 5 log killing for ESBL-producing E. coli and E. coli (ATCC
      25922); 4 log killing for MRSA, and 3 log killing for S. aureus (ATCC 25923). TBO
      at 80 microM, 30 Jcm(-2), only exhibited 3 log killing in MRSA and 2 log killing
      in S. aureus (ATCC 25923). TBO (400 microM, 30 Jcm(-2)) induced equal killing for
      ESBL-producing E. coli and E. coli (ATCC 25922). Our studied MRSA isolate
      responded better than S. aureus (ATCC 25923). Thus, pL-ce6-mediated PDI in other
      MRSA isolates deserves further investigation.

PMID- 17458676
TI  - Effect on carotid atherosclerosis of probucol plus levofloxacin for Chlamydia
      pneumoniae infection.
AB  - To investigate the effect of levofloxacin on carotid atherosclerosis, patients
      with hypercholesterolemia whose carotid atherosclerosis was not improved by
      probucol therapy (500 mg/day) for 24 months were enrolled. All patients were
      seropositive for anti C. pneumoniae IgA and/or IgG. Carotid atherosclerosis was
      evaluated by ultrasonic measurement of the maximum intima-media thickness (Max
      IMT). All subjects were prescribed three courses of levofloxacin (each course,
      400 mg/day for 2 weeks, followed by 14 days off drug treatment). At 12 months
      after combined therapy with probucol and levofloxacin, Max-IMT was significantly
      decreased compared with the value before treatment (P < 0.01). These results
      suggest that the combination therapy was effective for improving carotid
      atherosclerosis in C. pneumoniae-seropositive patients.

PMID- 17458677
TI  - Time courses of bacterial density in urine during antibacterial chemotherapy and
      influential factors in patients having positive bacteriuria with a complicated
      urinary tract.
AB  - A series of consecutive urine cultures was performed to determine the time points
      of elimination of bacteria from urine and the factors influencing these time
      points in patients receiving antimicrobial chemotherapy for positive bacteriuria.
      Between 1988 and 2000, 110 patients who had positive bacteriuria and received a 5
      day regimen of parenteral antibacterials were included in this study.
      Quantitative urine cultures were performed every 24 h throughout the therapy.
      Bacteria were identified; minimum inhibitory concentrations of antibacterial
      agents for causative bacteria were determined, and the bacteria were categorized
      as susceptible or nonsusceptible. The complexity of the urinary tract was graded
      as high or low. A multivariate Cox proportional hazards model was utilized to
      identify the factors that determined the time course of bacterial density in
      urine. Two penicillins, seven cephalosporins, five carbapenems and one
      fluoroquinolone were administered to 110 patients. The overall bacteriurial
      elimination rate at the end of treatment was 73% (80/110), and the most frequent
      day of elimination was day 1 (54%; 43/80), followed by day 2 (20%; 16/80). The
      significant factors for persistence of bacteriuria after chemotherapy were the
      presence of an indwelling catheter, a nonsusceptible pathogen, and high
      complexity of the urinary tract; risk ratios were: 2.398 (P = 0.0009), 2.227 (P =
      0.0020), and 2.113 (P = 0.0455), respectively, which also influenced the day of
      elimination. In conclusion, the efficacy of treatment and the time point of
      bacteriurial elimination were determined by the presence of a urinary catheter,
      drug susceptibility, and urinary complexity in patients with positive bacteriuria
      undergoing antibacterial chemotherapy.

PMID- 17458678
TI  - Current survey of urinary tuberculosis in Hokkaido, Japan.
AB  - Urinary tuberculosis has been rare in recent years and its diagnosis is difficult
      because there are no disease-specific symptoms. We tried to clarify the
      occurrence of urinary tuberculosis in recent years in our area. During the past 5
      years, there were 12 patients with urinary tuberculosis in the clinics that
      participated in this study. Their chief complaints were frequent voiding in 7
      patients and gross hematuria in 3 patients. They were diagnosed by nucleic acid
      amplification tests and imaging modalities such as excretory urography, computed
      tomography, and/or cystoscopy. Most of the patients received multidrug treatment
      and had relatively favorable treatment outcomes. There has been a small but
      neglected number of patients with urinary tuberculosis in recent years. We should
      keep this rare and difficult-to-diagnose disease in mind and suspect it when
      patients complain of longstanding urinary symptoms with no obvious cause.

PMID- 17458679
TI  - Is retention of a nasogastric tube after esophagectomy a risk factor for
      postoperative respiratory tract infection?
AB  - Between 1990 and 2004, 149 patients underwent esophagectomy with thoracotomy at
      our institution. Because the retention of a nasogastric tube postoperatively
      impedes expectoration, this practice was abolished in 1997, in order to reduce
      the risk of respiratory tract infection (RTI). Since 1998, we have instead
      performed gastrostomy for decompression. In this retrospective study, we compared
      the incidence of postoperative respiratory tract infection between these two
      groups. We previously demonstrated that the concordance between bacteria detected
      in the gastric juices and those detected in sputum was more than 70% in patients
      with postoperative RTI. In the present study, the incidence of postoperative
      respiratory tract infection was significantly higher in patients in whom a
      nasogastric tube was retained when compared to the rate in those for whom
      gastrostomy was performed instead (41.5% [34/82] vs 26.9% [18/67]; P = 0.045).
      The rate of other infections did not differ significantly between the two groups.
      We conclude that, in the postoperative management of esophagectomy, the retention
      of a nasogastric tube impedes expectoration. In addition, nasogastric tubes
      appear to increase the risk of postoperative RTI, considering the previous
      finding that the concordance of bacteria in sputum and gastric secretion was over
      70%.

PMID- 17458680
TI  - Adult Still's disease associated with cytomegalovirus infection.
AB  - A 77-year-old woman was admitted to our hospital complaining of high fever. The
      physical examination on admission indicated no abnormality. Although several
      antibiotics were administered, the spiking high fever was not alleviated. Two
      weeks after admission a macular rash appeared, and a high concentration of serum
      ferritin was observed. At this point, Still's disease was suspected, and the
      patient was referred to Nagasaki University Hospital. During the prescribed
      course of prednisolone, hepatic enzymes gradually increased to high titers
      accompanied by a positive test for cytomegalovirus (CMV) antigen. The CMV antigen
      disappeared after ganciclovir administration, and the concentration of serum
      ferritin decreased after steroid administration. In this report, we attempt to
      portray the relation between the pathogenesis of adult-onset Still's disease and
      the presence of CMV antigen.

PMID- 17458681
TI  - Occurrence of vancomycin-intermediate-resistant Staphylococcus aureus in Japan.
AB  - The Clinical and Laboratory Standards Institute (CLSI) amended the criteria for
      vancomycin susceptibility and resistance of Staphylococcus aureus in 2006. The
      earlier criteria had established that S. aureus with minimum inhibitory
      concentrations (MICs) of vancomycin of < or =4 microg/ml, 8 to 16 microg/ml, and
      > or =32 microg/ml were vancomycin-susceptible, -intermediate-resistant and 
      resistant, respectively. The revised recommendation states that bacteria showing
      vancomycin MICs of < or =2 microg/ml, 4 to 8 microg/ml, and > or =16 microg/ml
      are -susceptible, -intermediate-resistant, and -resistant, respectively. We
      examined, based on these new criteria, the vancomycin susceptibility of
      methicillin-resistant S. aureus (MRSA) strains isolated in Japan from 1978
      through 2005 at 17 general hospitals. The results showed that, among 2446 MRSA
      isolates tested, 8 were classified as intermediate-vancomycin-resistant (VISA).
      Re-examination of vancomycin susceptibility in these 8 strains in 2006 revealed
      that 6 strains showed a vancomycin MIC of 4 microg/ml, as tested by the agar
      dilution method, broth dilution methods, and E-test; the 2 other strains had lost
      the vancomycin resistance. Pulsed-field gel electrophoresis (PFGE) of the
      chromosomal DNA of these strains exhibited five unique profiles; 2 strains
      isolated from the same hospital were identical. These results revealed that at
      least five different types of VISA strains could be identified in Japan so far
      according to the new CLSI criteria. All these VISA strains had type II
      staphylococcal cassette chromosome, mec. This study revealed, for the first time
      in Japan, the presence of intermediate vancomycin-resistant MRSA in this country.

PMID- 17458682
TI  - Successfully treated nosocomial Stenotrophomonas maltophilia bacteremia following
      desensitization to trimethoprim-sulfamethoxazole.
AB  - Stenotrophomonas maltophilia has emerged as an important cause of morbidity and
      mortality in hospitalized patients. Because trimethoprim-sulfamethoxazole (TMP
      SMX) remains the most effective drug for the treatment of S. maltophilia
      infections, desensitization should be considered in patients with
      hypersensitivity to TMP-SMX.

PMID- 17458683
TI  - Structural development of self nano emulsifying drug delivery systems (SNEDDS)
      during in vitro lipid digestion monitored by small-angle X-ray scattering.
AB  - PURPOSE: To investigate the structural development of the colloid phases
      generated during lipolysis of a lipid-based formulation in an in vitro lipolysis
      model, which simulates digestion in the small intestine. MATERIALS AND METHODS:
      Small-Angle X-Ray scattering (SAXS) coupled with the in vitro lipolysis model
      which accurately reproduces the solubilizing environment in the gastrointestinal
      tract and simulates gastrointestinal lipid digestion through the use of bile and
      pancreatic extracts. The combined method was used to follow the intermediate
      digestion products of a self nano emulsified drug delivery system (SNEDDS) under
      fasted conditions. SNEDDS is developed to facilitate the uptake of poorly soluble
      drugs. RESULTS: The data revealed that a lamellar phase forms immediately after
      initiation of lipolysis, whereas a hexagonal phase is formed after 60 min. The
      change of the relative amounts of these phases clearly demonstrates that
      lipolysis is a dynamic process. The formation of these phases is driven by the
      lipase which continuously hydrolyzes triglycerides from the oil-cores of the
      nanoemulsion droplets into mono- and diglycerides and fatty acids. We propose
      that this change of the over-all composition of the intestinal fluid with
      increased fraction of hydrolyzed nanoemulsion induces a change in the composition
      and effective critical packing parameter of the amphiphilic molecules, which
      determines the phase behavior of the system. Control experiments (only the
      digestion medium) or the surfactant (Cremophor RH 40) revealed the formation of a
      lamellar phase demonstrating that the hexagonal phase is due to the hydrolysis of
      the SNEDDS formulation. CONCLUSIONS: The current results demonstrate that SAXS
      measurements combined with the in vitro dynamic lipolysis model may be used to
      elucidate the processes encountered during the digestion of lipid-based
      formulations of poorly soluble drugs for oral drug delivery. Thus the combined
      methods may act as an efficient screening tool.

PMID- 17458684
TI  - Quantitative bioanalytical methods validation and implementation: best practices
      for chromatographic and ligand binding assays.
AB  - The Third AAPS/FDA Bioanalytical Workshop, entitled "Quantitative Bioanalytical
      Methods Validation and Implementation: Best Practices for Chromatographic and
      Ligand Binding Assays" was held on May 1-3, 2006 in Arlington, VA. The format of
      this workshop consisted of presentations on bioanalytical topics, followed by
      discussion sessions where these topics could be debated, with the goal of
      reaching consensus, or identifying subjects where addition input or clarification
      was required. The discussion also addressed bioanalytical validation requirements
      of regulatory agencies, with the purpose of clarifying expectations for
      regulatory submissions. The proceedings from each day were reviewed and
      summarized in the evening sessions among the speakers and moderators of the day.
      The consensus summary was presented back to the workshop on the last day and was
      further debated. This communication represents the distillate of the workshop
      proceedings and provides the summary of consensus reached and also contains the
      validation topics where no consensus was reached.

PMID- 17458686
TI  - New insights in the interpretation of tryptophan fluorescence : origin of the
      fluorescence lifetime and characterization of a new fluorescence parameter in
      proteins: the emission to excitation ratio.
AB  - Origin of tryptophan fluorescence is still up to these days a quiz which is not
      completely solved. Fluorescence emission properties of tryptophan within proteins
      are in general considered as the result of fluorophore interaction within its
      environment. For example, a low fluorescence quantum yield is supposed to be the
      consequence of an important fluorophore-environment interaction. However, are we
      sure that the fluorophore has been excited upon light absorption? What if
      fluorophore excitation did not occur as the result of internal conformation
      specific to the fluorophore environment? Are we sure that all absorbed energy is
      used for the excitation process? Fluorescence lifetimes of Trp residues are
      considered to originate from rotamers or conformers resulting from the rotation
      of the indole ring within the peptide bonds. However, how can we explain the fact
      that in most of the proteins, the two lifetimes 0.5 and 3 ns, attributed to the
      conformers, are also observed for free tryptophan in solution? The present work,
      performed on free tryptophan and tyrosine in solution and on different proteins,
      shows that absorption and excitation spectra overlap but their intensities at the
      different excitation wavelengths are not necessarily equal. Also, we found that
      fluorescence emission intensities recorded at different excitation wavelengths
      depend on the intensities at these excitation wavelengths and not on the optical
      densities. Thus, excitation is not equal to absorption. In our interpretation of
      the data, we consider that absorbed photons are not necessary used only for the
      excitation, part of them are used to reorganize fluorophore molecules in a new
      state (excited structure) and another part is used for the excitation process. A
      new parameter that characterizes the ratio of the number of emitted photons over
      the real number of photons used to excite the fluorophore can be defined. We call
      this parameter, the emission to excitation ratio. Since our results were observed
      for fluorophores free in solution and present within proteins, structural
      reorganization does not depend on the protein backbone. Thus, fluorescence
      lifetimes (0.5 and 3 ns) observed for tryptophan molecules result from the new
      structures obtained in the excited state. Our theory allows opening a new way in
      the understanding of the origin of protein fluorescence and fluorescence of
      aromatic amino acids.

PMID- 17458685
TI  - AAPS-FDA workshop white paper: microdialysis principles, application and
      regulatory perspectives.
AB  - Many decisions in drug development and medical practice are based on measuring
      blood concentrations of endogenous and exogenous molecules. Yet most biochemical
      and pharmacological events take place in the tissues. Also, most drugs with few
      notable exceptions exert their effects not within the bloodstream, but in defined
      target tissues into which drugs have to distribute from the central compartment.
      Assessing tissue drug chemistry has, thus, for long been viewed as a more
      rational way to provide clinically meaningful data rather than gaining
      information from blood samples. More specifically, it is often the extracellular
      (interstitial) tissue space that is most closely related to the site of action
      (biophase) of the drug. Currently microdialysis (microD) is the only tool
      available that explicitly provides data on the extracellular space. Although
      microD as a preclinical and clinical tool has been available for two decades,
      there is still uncertainty about the use of microD in drug research and
      development, both from a methodological and a regulatory point of view. In an
      attempt to reduce this uncertainty and to provide an overview of the principles
      and applications of microD in preclinical and clinical settings, an AAPS-FDA
      workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from
      academia, industry and regulatory agencies presented their views on microD as a
      tool in drug research and development.

PMID- 17458689
TI  - Ozone therapy in induced endotoxemic shock. II. The effect of ozone therapy upon
      selected histochemical reactions in organs of rats in endotoxemic shock.
AB  - Mitochondria and lysosomes were evaluated by assessment of changes in activity of
      selected enzymes: lactate dehydrogenase (LDH), succinate dehydrogenase (SDH),
      adenosinetriphosphatase (ATPase), acid phosphatase (AcPase) and beta
      glucuronidase (BG) in rats under profound hypoxia induced by endotoxemic shock.
      The study was conducted on adult male Wistar rats. The animals formed the
      following four groups of 15 rats each: control animals (C);-rats receiving
      intraperitonally O(2)/O(3) (CO), rats receiving of Escherichia coli toxin (LPS)
      (CL); rats receiving LPS plus oxygen-ozone mixture (OL). Histoenzymatic
      examinations of liver, kidney, lungs, and heart muscle were performed.
      Lipopolysaccharide suppressed activities of all the enzymes except for LDH, the
      activity of which as high as a fourfold increase. The results demonstrated
      potent, stabilizing and regenerative effects of ozone therapy on body enzymatic
      processes in course of induced endotoxemic shock in rats, which might prove to be
      of clinical significance.

PMID- 17458690
TI  - Transesophageal echocardiography: a follow-up tool after catheter ablation of
      atrial fibrillation and interventional therapy of pulmonary vein stenosis and
      occlusion.
AB  - BACKGROUND: Pulmonary vein stenosis (PVS) has been described as a complication
      after primary catheter ablation of atrial fibrillation (Afib). The purpose of
      this study was to evaluate the utility of transesophageal echocardiography (TEE)
      as follow-up tool after catheter ablation of Afib and interventional therapy of
      PVS and pulmonary vein occlusion (PVO). METHODS: We report on 28 patients with
      stenosis (PVS) of 33 pulmonary veins (PVs) and total PVO of 4 veins complicating
      ablation of Afib assessed by angiography and/or magnetic resonance imaging (MRI).
      Subsequently, transseptal PV angiograms were performed, followed by
      recanalization of three totally occluded PVs and balloon dilatation of seven
      severe PVS (in four cases combined with PV stenting). PVs were analyzed by
      multiplane TEE in an intraindividual comparison of preablation/preintervention
      and follow-up measurements of mean and peak flow velocity, velocity time
      integrals, and diameters. RESULTS: Of a total of 28 patients, 14 had mild PVS (n
      = 14), 9 had moderate PVS (n = 10), 6 had severe PVS (n = 8), and 4 patients
      showed totally occluded PVs (n = 4). In multivariate analysis flow velocities and
      vessel diameters showed significant differences (mild, moderate, and severe PVS
      and PVO; p = 0.001). Interventional benefits of balloon dilatation (n = 10) and
      stent implantation (n = 4), as well as in-stent restenosis could be detected (p =
      0.014). In all recanalized vessels TEE showed reestablished flow. In occluded PVs
      no flow was detectable. The TEE vessel diameters correlated with angiography data
      (r = 0.87) and computed tomography/MRI (r = 0.90). CONCLUSIONS: TEE can be used
      as a follow-up tool after interventional therapy in patients after catheter
      ablation and acquired PVS/PVO. Restenosis/in-stent restenosis can be identified
      by analyzing the vessel diameters and blood flow characteristics.

PMID- 17458691
TI  - HIV-related stigma among people with HIV and their families: a qualitative
      analysis.
AB  - We examined the interconnectedness of stigma experiences in families living with
      HIV, from the perspective of multiple family members. Semi-structured interviews
      were conducted with 33 families (33 parents with HIV, 27 children under age 18,
      19 adult children, and 15 caregivers). Parents were drawn from the HIV Cost and
      Services Utilization Study, a representative sample of people in care for HIV in
      US. All of the families recounted experiences with stigma, including 100% of
      mothers, 88% of fathers, 52% of children, 79% of adult children, and 60% of
      caregivers. About 97% of families described discrimination fears, 79% of families
      experienced actual discrimination, and 10% of uninfected family members
      experienced stigma from association with the parent with HIV. Interpersonal
      discrimination seemed to stem from fears of contagion. Findings indicate a need
      for interventions to reduce HIV stigma in the general public and to help families
      cope with stigma.

PMID- 17458692
TI  - Effectiveness of zinc in modulating lithium induced biochemical and behavioral
      changes in rat brain.
AB  - 1. The purpose of the present study was to determine the effect of zinc on the
      status of various neurotransmitters as well as behavioral patterns of lithium
      treated rats. The study was designed with a view to find out whether zinc affords
      protection to brain against lithium toxicity. 2. Animals were segregated into
      four different groups. Animals in group I were fed with standard laboratory feed
      and water ad libitum and served as normal controls. Animals in group II and IV
      were given lithium in the form of lithium carbonate in their diet at a dose level
      of 1.1 g/Kg diet. Animals in group III and IV were given zinc treatment in the
      form of zinc sulfate at a dose level of 227 mg/L mixed in drinking water of
      animals. 3. The effects of all the treatments were studied for a duration of 1,
      2, and 4 months with regard to the parameters, which included estimation of
      serotonin and dopamine concentrations as well as the activity of
      acetylcholinesterase in cerebral cortex of rat brain. Further, passive avoidance,
      active avoidance, and behavior despair tests were conducted to assess the short
      term memory, cognitive behavior, and psychomotor dysfunction of the animals,
      respectively. 4. Initially, a decrease in the acetylcholinesterase activity was
      reported in cerebral cortex followed by an increase in the enzyme activity after
      2 and 4 months of lithium treatment. Serotonin concentration significantly
      decreased after 2 and 4 months of lithium treatment, whereas dopamine
      concentration increased significantly after 4 months of lithium treatment. Zinc
      administration to the lithium-treated group significantly improved the
      acetylcholinesterase activity as well as the concentration of dopamine and
      serotonin. Further, lithium-treated rats showed an increase in depression time as
      compared to normal controls both after 1 and 4 months of treatment. Short-term
      memory significantly improved in lithium-treated rats in all treatment groups.
      However, no change in the cognitive behavior of the animals was reported after
      lithium treatment. Zinc co-administration with lithium significantly improved the
      short-term memory and cognitive functions of the animals. From the above results
      it can be concluded that zinc proved beneficial in altering the status of
      neurotransmitters as well as the behavior patters of the animals treated with
      both short and long-term lithium therapy.

PMID- 17458693
TI  - A Phase 2 study of perifosine in advanced or metastatic breast cancer.
AB  - BACKGROUND: First- and second-line chemotherapy with anthracyclines and taxanes
      in metastatic breast cancer yield a modest improvement in survival with
      potentially significant toxicity. Subsequent lines of chemotherapy yield response
      rates of 20-25%, with an unknown impact on survival. Perifosine, an oral
      alkylphospholipid structurally related to miltefosine, has marked activity
      against breast cancer cell lines and xenograft models, with broad spectrum
      cellular effects. OBJECTIVES: To determine the efficacy and toxicity of
      perifosine in patients with metastatic breast cancer patients after up to 2 lines
      of prior chemotherapy for advanced disease. METHODS: 18 patients were enrolled,
      and 17 treated, using a loading/maintenance dose schedule, (day 1, 300 mg,
      maintenance 150 mg days 2-21) every 28 days, until disease progression or
      unacceptable toxicity. RESULTS: Median age of patients was 54 (28-69), 16/17 were
      female, ECOG performance status was 0/1 in 16 patients. Fifteen received at least
      1 prior chemotherapy regimen for metastatic disease (maximum 2). A median of 2
      cycles (range 1-13) was administered per patient. Sixteen were evaluable for
      response: 2 had SD for 4 cycles, 1 SD for 13 cycles, 13 progressed by cycle 2.
      Grade 3/4 drug-related non-hematologic toxicities include: diarrhea (2), vomiting
      (2), nausea (2), fatigue (2) and anorexia (1). No grade 3/4 hematologic
      toxicities were seen. Median time to progression was 8 weeks (7-15 weeks).
      CONCLUSION: No objective responses were seen in this group of pretreated
      metastatic breast cancer patients. Disease stabilization was observed in 19% at 2
      months.

PMID- 17458694
TI  - Detection of the CHEK2 1100delC mutation by MLPA BRCA1/2 analysis: a worthwhile
      strategy for its clinical applicability in 1100delC low-frequency populations?

PMID- 17458695
TI  - CYP1B1 and predisposition to breast cancer in Poland.
AB  - BACKGROUND: The CYP1B1 gene is a polymorphic member of the P450 gene family and
      is considered to be a candidate gene for cancers of various types. OBJECTIVE: We
      inquired whether four SNPs in the CYP1B1 gene, alone or in combination, might be
      associated with breast cancer risk in Poland. METHODS: We genotyped 2017 cases of
      breast cancer and 876 controls, for four SNPs in the CYP1B1 gene. Genotype and
      haplotype frequencies were compared in cases and controls. RESULTS: In
      combinations of the R48G, A119S and L432V SNPs, four of the eight CYP1B1
      haplotypes were more common in controls than in cases and each of these appeared
      to have a significant protective effect. A large reduction in risk was observed
      for women who were homozygous for one of these four haplotypes (OR = 0.2; 95%; CI
      = 0.05-0.5; P = 0.001) compared to women who were homozygous for the most common
      haplotype. In contrast, women who were homozygous for the GTC haplotype were at
      increased risk (OR = 1.5; 95%; CI = 1.0-2.1; P = 0.03) compared to women with the
      most common haplotype. CONCLUSIONS: The CYP1B1 gene appears to influence breast
      cancer susceptibility in Poland.

PMID- 17458696
TI  - Truncations and functional carboxylic acid residues of yeast processing alpha
      glucosidase I.
AB  - Yeast alpha-glucosidase I (Cwh41p) encoded by CWH41 is an endoplasmic reticulum
      (ER) membrane-bound glycoprotein (833 residues), which plays an important role in
      the early steps of the N-glycosylation pathway. In this study functional
      expression of three truncated fragments of Cwh41p, all containing the catalytic
      region, was investigated. Cwht1p (E35-F833), with deletion of the N-terminus and
      transmembrane domain, was expressed as a catalytically active fragment while R320
      F833(Cwht2p) and M526-F833 (Cwht3p) were not detected. Significantly higher
      glucosidase I activity was found in a soluble extract from yeast overexpressing
      CWHT1 (1,400 U/g biomass) than yeast overexpressing CWH41 (300 U/g biomass).
      Cwht1p was purified as a soluble 94 kDa non-glycosylated protein with a specific
      activity (3,600 U/mg protein) comparable to that of the soluble alpha-glucosidase
      I (3000 U/mg protein). These findings indicate that the active conformation of
      the enzyme is not dependent on protein glycosylation and suggest that the M1-I28
      region of Cwh41p carries an ER-targeting signal sequence. In addition, two highly
      conserved carboxylic acid residues, E580 and D584 of Cwht1p (corresponding to
      E613 and D617 of Cwh41p), located within the catalytic domain of yeast enzyme
      were subjected to mutation. Substitution of each residue with Ala resulted in low
      expression and undetectable glucosidase I activity. These findings indicate that
      E613 and D617 play a crucial role in maintaining alpha-glucosidase I activity.

PMID- 17458697
TI  - Association among C-reactive protein, Fatty liver disease, and cardiovascular
      risk.
AB  - Nonalcoholic fatty liver disease (NAFLD) is associated with several metabolic
      disturbances involving inflammation. Ultrasensitive C-reactive protein (uCRP), a
      marker of coronary heart disease and other chronic diseases, has not been
      investigated in NAFLD. We tested the relationship between uCRP and NAFLD in
      middle-aged asymptomatic subjects, independently of other metabolic disturbances
      associated with metabolic syndrome and cardiovascular risk. We compared 310
      subjects with steatosis visible on ultrasound (cases) with 630 and without
      (controls). Body mass index (BMI), blood pressure and serum levels of uCRP,
      glucose, lipids, and lipoproteins were measured in all subjects. Differences
      between groups and the impact of serum uCRP levels were tested by univariate and
      multivariate logistic regression analysis. Cases were statistically different
      from controls in the frequency of metabolic syndrome (66.4% vs. 26.7%; P <
      0.001). Cases were significantly older (P < 0.001), and had significantly higher
      values for BMI, glucose, total cholesterol and triglycerides (P < 0.001), and
      mean uCRP concentrations (4.5 vs. 2.79 mg/L; P < 0.001). By univariate analysis,
      variables significantly associated with cases were glucose (OR, 4.09; 95% CI,
      2.98-5.61), BMI (OR 5.54; 95% CI, 4.09-7.49), and uCRP (OR 7.06; 95% CI, 4.51
      11.02). By multivariate analysis, uCRP levels were associated with hepatic
      steatosis (OR 5.83; 95% CI, 3.07-11.06). Cardiovascular risk was also higher in
      subjects with NAFLD (4.7 vs. 2.8). Subjects with hepatic steatosis showed an
      increased concentration of uCRP independently of other metabolic disturbances;
      this suggests an increased risk of cardiovascular diseases and could be used as a
      marker of chronic inflammation.

PMID- 17458698
TI  - A translational bioengineering course provides substantial gains in civic
      scientific literacy.
AB  - A growing number of essential consumer choices and public policy issues require a
      basic level of scientific literacy. Recent studies suggest as many as three
      quarters of adults are unable to read and understand news accounts of scientific
      advances and controversies. In response to this challenge, a new course for non
      science majors, Bioengineering and World Health, was designed to improve
      biomedical literacy. The goal of this study was to compare scientific literacy of
      students enrolled in the course to that of two groups of students who had not
      taken the course; the first control group included students majoring in
      Biomedical Engineering (BME), the second included those majoring in Liberal Arts
      or Natural Sciences. Small group interviews in which students discussed science
      news accounts from the popular press were used to assess scientific literacy.
      Students in Bioengineering and World Health showed increasing scientific literacy
      throughout the course. At the conclusion of Bioengineering and World Health, the
      mean scientific literacy of students in the course was significantly higher than
      that in both control groups. Students were stratified by the number of semester
      credit hours completed in science, math, engineering and technology (SME&T)
      courses. Regardless of number of SME&T hours completed, the mean scientific
      literacy of students completing Bioengineering and World Health was equivalent to
      that of BME majors who had completed more than 60 semester credit hours of SME&T
      coursework, suggesting that a single introductory course can significantly
      influence scientific literacy as measured by participant's ability to discuss
      medical innovations from a common news source.

PMID- 17458699
TI  - chip artifact CORRECTion (caCORRECT): a bioinformatics system for quality
      assurance of genomics and proteomics array data.
AB  - Quality assurance of high throughput "-omics" data is a major concern for
      biomedical discovery and translational medicine, and is considered a top priority
      in bioinformatics and systems biology. Here, we report a web-based bioinformatics
      tool called caCORRECT for chip artifact detection, analysis, and CORRECTion,
      which removes systematic artifactual noises that are commonly observed in
      microarray gene expression data. Despite the development of major databases such
      as GEO arrayExpress, caArray, and the SMD to manage and distribute microarray
      data to the public, reproducibility has been questioned in many cases, including
      high-profile papers and datasets. Based on both archived and synthetic data, we
      have designed the caCORRECT to have several advanced features: (1) to uncover
      significant, correctable artifacts that affect reproducibility of experiments;
      (2) to improve the integrity and quality of public archives by removing
      artifacts; (3) to provide a universal quality score to aid users in their
      selection of suitable microarray data; and (4) to improve the true-positive rate
      of biomarker selection verified by test data. These features are expected to
      improve the reproducibility of Microarray study. caCORRECT is freely available
      at: http://caCORRECT.bme.gatech.edu.

PMID- 17458700
TI  - Models of flow-induced loading on blood cells in laminar and turbulent flow, with
      application to cardiovascular device flow.
AB  - Viscous shear stress and Reynolds stress are often used to predict hemolysis and
      thrombosis due to flow-induced stress on blood elements in cardiovascular
      devices. These macroscopic stresses are distinct from the true stress on an
      individual cell, which is determined by the local microscale flow field. In this
      paper the flow-induced stress on blood cells is calculated for laminar and
      turbulent flow, using simplified models for cells and for turbulent eddies. The
      model is applied to estimate shear stress on red blood cells in flow through a
      prosthetic heart valve, using the energy spectral density measured by Liu et al.
      [J. Biomech. Eng. 122:118-124, 2000]. Results show that in laminar flow, the
      maximum stress on a cell is approximately equal to the macroscopic viscous shear
      stress. In turbulent flow through a prosthetic heart valve, the estimated root
      mean square of flow-induced stress on a cell is at least an order of magnitude
      less than the Reynolds stress. The results support the hypothesis that smaller
      turbulent eddies cause higher stress on cells. However, the stress due to an eddy
      depends on the velocity scale of the eddy as well as its length scale. For the
      heart valve flow investigated, turbulence contributes to flow-induced stress on
      cells almost equally across a broad range of the frequency spectrum. The model
      suggests that Reynolds stress alone is not an adequate predictor of cell damage
      in turbulent flow, and highlights the importance of the energy spectral density.

PMID- 17458701
TI  - Treatment of a pituitary metastasis from a neuroendocrine tumour: case report and
      literature review.
AB  - Herein we report a rare case of a pituitary metastasis from a neuroendocrine
      tumour mimicking an adenoma. Moreover, starting from this unusual case, the
      relevant literature concerning the diagnosis and management of patients with
      metastasis at pituitary level is reviewed. A 69-year-old woman was admitted to
      our Unit for severe headache, diplopia, and critical visual field impairment. MRI
      showed a large pituitary mass compressing the optic chiasm and infiltrating the
      cavernous sinus. Trans-sphenoidal biopsy revealed a pituitary metastasis from a
      neuroendocrine tumour, in line with the multiple liver lesions that were already
      considered metastases from an ileal primary neuroendocrine tumour. In vitro
      receptor characterisation of both pituitary and liver tissues by
      immunohistochemistry showed a heterogeneous somatostatin receptor subtype
      pattern, with a predominant expression of sst(2) within the pituitary lesion.
      However, the liver metastasis receptor profile was completely different from the
      pituitary. Octreotide LAR was administered first, followed by receptor
      radiometabolic therapy with radiolabelled somatostatin analogues ((90)Y-DOTATOC
      and (177)Lu-DOTATATE). After 16 months, MRI showed a significant shrinkage of the
      sellar mass. Moreover, disappearance of diplopia and visual defects, together
      with a considerable improvement in quality of life were gradually recorded. To
      our knowledge, this is the first case of combined treatment using "cold" and
      radiolabelled octreotide in a pituitary metastasis from a neuroendocrine tumour.

PMID- 17458702
TI  - Growth hormone measurements in the diagnosis and monitoring of acromegaly.
AB  - Before the availability of immunoassays for IGF-I, growth hormone (GH)
      measurement was the sole method used in the biochemical assessment of acromegaly.
      IGF-I has since been established as the most reliable biochemical indicator of
      acromegaly. The last 25 years has seen important advances in the understanding of
      the neuroregulation and in the characterization of GH secretion in acromegaly.
      The availability of supersensitive GH has changed many aspects of the
      interpretation of GH-value in the management of acromegaly. Hypersecretion and
      abnormal neuroregulation characterize GH secretion in acromegaly. GH can be
      measured in many ways: as a single random sample, as multiple samples, either
      spontaneously or as an integral part of a dynamic test. These approaches give
      useful information on diagnosis, therapy, and prognosis. There is a place for
      measuring GH in the management of acromegaly although it complements that of IGF
      I.

PMID- 17458703
TI  - Pituitary abscess: a report of two cases.
AB  - Pituitary abscess (PA) is an infrequent disease, which consists of an infection
      within the sella turcica that might be life-threatening. We present here two
      cases of this rare entity. Case 1: A 53-year-old woman was followed for an
      incidentally found pituitary cyst. Six years later the cyst enlarged and
      transsphenoidal surgery was performed. Two years later, the patient developed
      sudden onset of intense headache and nausea. The MRI showed a 2 by 2.5 cm sellar
      and suprasellar mass, that enhanced peripherally with gadolinium contrast and
      became hyperintense in T2-weighted images, suggesting a new-onset cystic lesion.
      During transsphenoidal surgery, large amounts of purulent material were drained
      from the sella. The cultures were positive for Klebsiella Ozaenae. Case 2: A 63
      year-old woman, 4 years after transsphenoidal resection of a GH-secreting
      macroadenoma, developed a new sellar 2.6 cm cystic mass. On re-operation,
      purulent material was drained from the sella. The lesion persisted on the MRI and
      visual acuity worsened so a repeat pituitary decompression was carried out 6
      months later, obtaining the same pathological results. Three years later, the MRI
      still shows the same mass. She feels well and her physical examination and
      clinical history are unremarkable. These cases illustrate the difficulties in the
      diagnosis and management of this rare entity.

PMID- 17458704
TI  - Social determinants of the health of urban populations: methodologic
      considerations.
AB  - A full understanding of the role of the urban environment in shaping the health
      of populations requires consideration of different features of the urban
      environment that may influence population health. The social environment is key
      to understanding the way in which cities affect the health of populations. Social
      determinants of health (SDH) are important, generally, yet can have different
      effects in different settings from urban to rural, between countries, between
      cities, and within cities. Failure to acknowledge, and more importantly, to
      understand the role of SDH in health and access to health and social services
      will hamper any effort to improve the health of the population. In this paper, we
      will briefly summarize a few key SDH and their measurement. We will also consider
      methodologic tools and some methodologic challenges. The concepts presented here
      are broadly applicable to a variety of settings: developed and developing
      countries, slum areas, inner cities, middle income neighborhoods, and even higher
      income neighborhoods. However, our focus will be on some of the more vulnerable
      urban populations who are most profoundly affected by SDH.

PMID- 17458706
TI  - Intravesical fat entrapment as a cause of failure of extraperitoneal bladder
      perforation to heal spontaneously.
AB  - We report a case of intravesical fat entrapment leading to failure of
      extraperitoneal bladder perforation to heal spontaneously. A 68-year-old woman
      underwent trans-abdominal hysterectomy complicated by an extraperitoneal bladder
      perforation. Despite prolonged catheterization, cystographic leakage persisted
      after 3 months. Bladder imaging and cystoscopy demonstrated a mass of perivesical
      pelvic fat protruding into the bladder cavity. The patient was symptomatic with
      pain and persistent urinary tract infection with episodes of sepsis. A
      transurethral resection of the mass was performed which led to bladder healing
      and resolution of symptoms.

PMID- 17458707
TI  - Clinical decision support systems and antibiotic use.
AB  - AIM: To review and appraise randomised controlled trials (RCT) and 'before and
      after' studies published on clinical decision support systems (CDSS) used to
      support the use of antibiotics. METHODS: A literature search was carried out in
      October 2006 using MEDLINE including Medical Subject Heading (MeSH) terms (1966
      2006), EMBASE (Excerpta Medica, 1980-2006) and International Pharmaceutical
      Abstracts (IPA, 1970-2006) using the combinations of the following terms:
      (Decision support systems) or (CDSS) AND (antibiotics) or (anti-infectives) or
      (antibacterials) or (antimicrobials). Only English language papers were selected.
      Editorials, letters and case reports/series were excluded. The reference sections
      of all retrieved articles were also searched for any further relevant articles.
      RESULTS: Forty articles were identified. Five RCT and six 'before and after'
      studies were retrieved. In the RCTs, three studies used computer-based CDSS, one
      paper-based CDSS and one a combination of both. Two studies were conducted in
      primary care and three within secondary care. The primary outcomes for each study
      were different and only three studies were significant in the favour of the use
      of CDSS. 'Before and after' studies were used where RCT were not feasible. One
      'before and after' study was excluded because it did not include any control
      group. The remaining five included historical control groups and evaluated the
      use of computer-based CDSS within secondary care. Their primary outcomes also
      varied but all concluded significant benefits of CDSS. Only three of ten studies
      were conducted outside the USA; one in Switzerland and two in Australia.
      CONCLUSION: CDSS could be a powerful tool to improve clinical care and patient
      outcomes. It presents a promising future for optimising antibiotic use. However,
      it is difficult to generalise as most studies were conducted in the United
      States. Although RCT are the 'gold standard' in research, they may not be
      feasible to conduct. Realising that different study designs answer different
      questions would allow researchers to choose the most appropriate study design to
      evaluate CDSS in a specified setting.

PMID- 17458708
TI  - Bovine mucopolysaccharidosis type IIIB.
AB  - Mucopolysaccharidosis IIIB, an autosomal recessive lysosomal storage disorder of
      heparan sulfate caused by mutations in the alpha-N-acetylglucosaminidase (NAGLU)
      gene, was recently discovered in cattle. Clinical signs include progressive
      ataxia, stumbling gait, swaying and difficulty in balance and walking. These
      clinical signs are usually first observed at approximately 2 years of age and
      then develop progressively over the lifespan of the animals. Affected bulls were
      found to be homozygous for the missense mutation E452K (c.1354G > A). The
      availability of mutational analysis permits screening for the NAGLU mutation to
      eradicate this mutation from the cattle breeding population.

PMID- 17458709
TI  - High incidence of autoantibodies in Fabry disease patients.
AB  - Fabry disease (FD) is an X-linked disorder of glycosphingolipid catabolism that
      results from a deficiency of the lysosomal enzyme alpha-galactosidase A. This
      defect leads to the accumulation of its substrates, mainly globotriaosylceramide,
      in lysosomes of cells of different tissues. Different studies have shown the
      involvement of immunopathologies in different sphingolipidoses. The coexistence
      of FD and immune disorders such as systemic lupus erythematosus, rheumatoid
      arthritis and IgA nephropathy, has been described in the literature. The aim of
      this study was to evaluate the prevalence of a group of autoantibodies in a
      series of Argentine FD patients. Autoantibodies against extractable nuclear
      antigens (ENAs), double-stranded DNA, anticardiolipin and phosphatidylserine were
      assayed by ELISA. Lupus anticoagulants were also tested. Fifty-seven per cent of
      the samples showed reactivity with at least one autoantigen. Such reactivities
      were more frequent among males than among females. Antiphospholipid
      autoantibodies were detected in 45% of our patients. The high rate of thrombosis
      associated with FD could be related, at least in part, to the presence of
      antiphospholipid autoantibodies in Fabry patients. We found the presence of ENAs,
      which are a characteristic finding of rheumatological diseases, previous a
      frequent misdiagnosis of FD, in around 39% of the cases. The detection of a high
      level of autoantibodies must be correlated clinically to determine the existence
      of an underlying autoimmune disease. With the recent development of therapy, the
      life expectancy in FD will increase and autoimmune diseases might play an
      important role in the morbidity of FD.

PMID- 17458710
TI  - In vitro determination of phagocytosis and intracellular killing of Aspergillus
      species by mononuclear phagocytes.
AB  - We investigated phagocytosis and intracellular killing of clinical and
      environmental isolates of Aspergillus spp. by human monocyte-derived macrophages
      (MDMs). Serial pathogens such as Aspergillus fumigatus, Aspergillus flavus and
      Aspergillus terreus were examined with a microbiological assay. Phagocytosis for
      resting conidia of Aspergillus spp. was similar for all isolates tested. During
      30 min of incubation phagocytosis ranged from 49.9% to 85.5% for clinical
      isolates and from 40.3% to 87.1% for environmental isolates. MDMs killed A.
      fumigatus, A. flavus and A. terreus conidia after ingestion for 120 min, as shown
      by a decrease in colony forming units (cfu) count of intracellular fungi. The
      killing index for all isolates of Aspergillus spp., ranged from 12.1 +/- 1.1% to
      90.3 +/- 10.4%; isolate-dependent (P < 0.01) differences against the fungicidal
      action of MDMs were observed. In conclusion, significant differences were noted
      for killing indices between several strains of Aspergillus spp. whereas
      phagocytosis was similar for all isolates tested in vitro. No differences were
      observed within environmental and clinical isolates.

PMID- 17458711
TI  - Inhibition of orthotopic osteosarcoma growth and metastasis by multitargeted
      antitumor activities of pigment epithelium-derived factor.
AB  - Osteosarcoma is major cause of cancer-related death in the pediatric age group,
      and this is due to the development of pulmonary metastases that fail to be
      eradicated with current treatment regimes. Although there have been significant
      improvements in the long-term survival of such patients, 25-50% with initially
      non-metastatic disease, subsequently develop metastases and this remains the
      major cause of death for these patients. In this study, we report the multimodal
      activity of pigment epithelium-derived factor (PEDF) in inhibiting osteosarcoma
      growth, angiogenesis and metastasis. In vitro, we found that administration of
      recombinant PEDF (rPEDF) on two osteosarcoma cell lines (rat UMR 106-01 and human
      SaOS-2) significantly reduced tumor cell proliferation and increased apoptosis,
      as well as decreased cell invasion, angiogenesis, and increased adhesion to
      collagen type-1. Administration of rPEDF upregulated the mRNA expression of
      phenotypic osteoblast differentiation markers (ALP, pro-alpha(1) collagen and
      osteocalcin) in a pre-osteoblastic cell line, UMR 201, and also increased
      mineralized nodule formation in both UMR 106-01 and SaOS-2. In vivo, rPEDF
      dramatically suppressed primary osteosarcoma growth and the development of
      macroscopic pulmonary metastases in an orthotopic model of human osteosarcoma
      (SaOS-2). Interestingly, no activity was seen in tumors grown subcutaneously,
      suggesting a paracrine interaction between PEDF and the bone microenvironment.
      Preliminary pharmacoevaluation studies demonstrated rPEDF stability within media
      containing serum and osteosarcoma cells, and no gross systemic toxicity was
      observed in vivo with rPEDF administration. These results suggest that PEDF is
      emerging as an attractive and clinically appealing drug candidate for the
      treatment of osteosarcoma.

PMID- 17458713
TI  - A look back at my stapp conferences through the years.

PMID- 17458712
TI  - Enhancement of hyperthermia-induced apoptosis by a new synthesized class of furan
      fused tetracyclic compounds.
AB  - The combined effects of hyperthermia (44 degrees C, 20 min) or X-rays (10 Gy) and
      a new class of furan-fused tetracyclic synthesized compounds (DFs), on apoptosis
      in human lymphoma U937 cells were investigated. Among the tested compounds (DF1
      approximately 6), the combined treatment of 10 microM DF with TIPS
      (triisopropylsilyloxy) (Designated #3 DF3) and hyperthermia showed the largest
      potency to induce DNA fragmentation at 6 h after hyperthermia but no enhancement
      was observed if it was combined with X-rays. Enhancement of hyperthermia-induced
      apoptosis by DF3 in a dose-dependent manner was observed. When the cells were
      treated first with DF3 at a nontoxic concentration of 20 microM, and exposed to
      hyperthermia afterwards, a significant enhancement of heat-induced apoptosis was
      evidenced by DNA fragmentation, morphological changes and phosphatidylserine
      externalization. The activation of Bid, but no change of Bax and Bcl-2 were
      observed after the combined treatment. The release of cytochrome c from
      mitochondria to cytosol, which was induced by hyperthermia, was enhanced by DF3.
      Mitochondrial transmembrane potential was decreased and the activation of caspase
      3 and caspase-8 was enhanced in the cells treated with the combination.
      Externalization of Fas was observed following the combined treatment. Flow
      cytometry revealed rapid and sustained increase of intracellular superoxide due
      to DF3, and showed subsequent and transient increase in the formation of
      intracellular hydrogen peroxide (H(2)O(2)), which was further increased when
      hyperthermia was combined. These results indicate that the intracellular
      superoxide and H(2)O(2) generated by DF3 enhance the hyperthermia-induced
      apoptosis via the Fas-mediated mitochondrial caspase-dependent pathway.

PMID- 17458714
TI  - The effect of mass, stiffness and geometry on injury outcome in side impacts - a
      parametric study.
AB  - This paper reports on a cooperative research project between the Australian
      Department of Transport and Regional Services and Transport Canada. This project
      was a parametric study aimed at better understanding the effects on side impact
      injury risk of: * Trolley mass * Barrier stiffness * Barrier stiffness
      distribution * Barrier face height above ground * Crabbed or perpendicular impact
      * Impact Speed The following observations on injury risk can be made from the
      tests: * The 2 largest effects for the driver are increasing the height of the
      barrier face (mainly thoracic) and test speed (all body regions). * Increasing
      the trolley mass, with a bullet / target mass ratio less than 1, has the effect
      of increasing only the pubic force. * Doubling the barrier stiffness increases
      injury risk in only the pelvic area. * The custom high and stiff element
      (attempting to replicate an SUV) increases both pelvic and abdominal loading.

PMID- 17458715
TI  - Assessment of injury risk to children from side airbags.
AB  - Static out-of-position tests were performed to identify the potential for injury
      as a function of position, airbag type and vehicle seat characteristics. Seat and
      door mounted airbags, head curtains and head tubes were evaluated. Out-of
      position testing was carried out with the Hybrid III 3 year old, 6 year old and
      the TNO Q3 3 year old child dummies. In-position tests and a dynamic test were
      conducted to monitor child seat and airbag interactions and to confirm that
      properly restrained children would not be exposed to undue risk from a deploying
      side airbag. Results of the out-of-position testing suggest that current side
      airbag designs may cause serious and/or fatal neck and chest injuries. In
      position static testing with child seats suggested a potential for intrusion into
      the child occupant space leading to structural damage of the car seat.

PMID- 17458717
TI  - On the development of survival criteria for rate sensitive materials.
AB  - The evaluation and mitigation of injury in the automotive crash environment is
      often achieved by monitoring and limiting the magnitude of forces and/or moments
      being applied to or transmitted through dummy structures representing particular
      portions of the human anatomy. Examples of body areas where this is the practice
      are the neck, the thoracic and lumbar spine, the pelvis, as well as the upper and
      lower extremities. Implicit within this process is the assumption that the
      observed forces are directly proportional to local failure metrics such as stress
      and/or strain. However, a variety of experimental efforts have demonstrated that
      many of these anatomical structures exhibit, to various degrees, viscoelastic
      behavior and time or rate dependent failure properties. This work develops a
      methodology that generalizes the results of various experimental observations.
      First, a particular material's viscoelastic constitutive properties are
      mathematically characterized by developing a constitutive relationship relating
      experimentally observed stress time histories to applied strain, and strain rate
      time histories. This constitutive relationship and a novel technique of "back
      integration" are employed to develop the material's creep compliance response. A
      Duhamel Integral relationship is used to predict the material's actual strain
      time history given its observed stress-rate time history and creep compliance
      characteristic. This then allows casting the material's loading history into its
      actual time dependent stress/strain space and determining if failure conditions
      have been exceeded. Both the theoretical development of this methodology and the
      effects of its application to real world crash circumstances are presented.

PMID- 17458716
TI  - Comparative Evaluation of the Q3 and Hybrid III 3-Year-Old Dummies in Biofidelity
      and Static Out-of-Position Airbag Tests.
AB  - A comparison of the Q3 and Hybrid III 3-year-old crash test dummies is presented
      in this paper. The performance of the dummies were compared in sixty biofidelity
      tests, seventy-seven static out-of-position airbag tests and sixty-three
      calibration tests. Various time histories and other data pertaining to
      accelerations, deflections, forces and moments are compared. In addition, the
      ease of positioning, handling, and the durability of the dummies in various out
      of-position test configurations was assessed. Both the Q3 and Hybrid III 3-year
      old dummies were calibrated to their respective specifications. The Hybrid III 3
      year-old met its calibration requirements, while the Q3 did not always meet its
      own calibration requirements. The calibration specifications of the Q3 dummy need
      to be re-examined and possibly refined. The biofidelity of the Q3 and Hybrid III
      3-year-old dummies were evaluated in both frontal and lateral test modes. Each
      dummy was evaluated against its own and the other's specified requirements, when
      possible. In the frontal test mode, the Hybrid III 3-year-old acceptably met all
      of its requirements. The Q3 dummy did not meet all of its own frontal biofidelity
      requirements. Based on these results, the Hybrid III 3-year-old is more
      biofidelic for primarily frontal loading conditions. With respect to the lateral
      biofidelity specifications, neither the Hybrid III 3-year-old nor the Q3 dummy
      met the requirements for the thorax and pelvis tests performed. Both dummies met
      the head drop requirements. Neither dummy is recommended for lateral loading
      conditions. For lateral testing where only the head is impacted, the Hybrid III 3
      year-old could be used. In general, the responses of both dummies were repeatable
      in both the frontal and lateral biofidelity tests performed. The Hybrid III 3
      year-old and the Q3 dummies were evaluated in static out-of-position airbag tests
      with three different side airbag systems (two seat-mounted and one door-mounted
      system), and one frontal passenger airbag system. Throughout this testing, the Q3
      resultant head accelerations exhibited an excessive amount of high-frequency
      noise causing this dummy to be unacceptable for static out-of-position airbag
      testing. No significant issues were found with the Hybrid III 3-yearold. It was
      also determined that the Q3 dummy was more difficult to position repeatedly than
      the Hybrid III 3-yearold. This was due to the dummy's construction and its lack
      of rigid landmarks.

PMID- 17458718
TI  - Improved neck injury risk curves for tension and extension moment measurements of
      crash dummies.
AB  - This paper describes improvements made to the injury risk curves for peak neck
      tension, peak neck extension moment and a linear combination of tension and
      extension moment that produce peak stress in the anterior-longitudinal ligament
      at the head-to-neck junction. Data from previously published experiments that
      correlated neck injuries to 10-week-old, anesthetized pigs and neck response
      measurements of a 3-year-old child dummy that were subjected to similar airbag
      deployments are updated and used to generate Normal probability curves for the
      risk of AIS >/= 3 neck injury for the 3-year-old child. These curves are extended
      to other sizes and ages by normalizing for neck size. Factors for percent of
      muscle tone and ligamentous failure stress as a function of age are incorporated
      in the risk analysis. The most sensitive predictor of AIS > 3 neck injury for
      this data set is peak neck tension. If two possible outliers are deleted from the
      data set, then the combined criterion of extension moment and axial force becomes
      the most sensitive predictor which is consistent with expectations.

PMID- 17458719
TI  - Child neck strength characteristics using an animal model.
AB  - The purpose of this study was to determine neck strength characteristics of
      children indirectly using scaling relationships through a caprine animal model.
      Because of the necessity to evaluate airbag designs for injury risk to the out-of
      position child, a strong foundation of experimental data is needed to obtain
      appropriate tolerance values. Cadaver caprine cervical spines of different ages
      were tested mechanically in nondestructive bending and destructive tensile modes.
      Injuries induced in destructive testing such as endplate failure and ligament
      tears were consistent with clinical observations. Specimens demonstrated
      statistically significant increased strength characteristics with age. Scaling
      relationships were developed with respect to the adult specimens. For the tensile
      failure load the scaling percentages were 78%, 38%, 20%, and 12% for the twelve-,
      six-, three-, and one-year-old, respectively. The tensile stiffness parameter
      yielded slightly higher scale factors of 85%, 54%, 23%, and 17%, whereas the
      bending stiffness parameter resulted in 62%, 57%, 15%, and 11% values for twelve
      , six-, three-, and one-yearold age groups, respectively. The caprine model
      therefore, suggests that tolerance values for the oneand three-year-old may be
      lower than the values obtained using current scaling techniques.

PMID- 17458720
TI  - Tensile properties of the human muscular and ligamentous cervical spine.
AB  - Tensile neck injuries are amongst the most serious cervical injuries. However,
      because neither reliable human cervical tensile tolerance data nor tensile
      structural data are currently available, the quantification of tensile injury
      risk is limited. The purpose of this study is to provide previously unavailable
      kinetic and tolerance data for the ligamentous cervical spine and determine the
      effect of neck muscle on tensile load response and tolerance. Using six male
      human cadaver specimens, isolated ligamentous cervical spine tests (occiput - T1)
      were conducted to quantify the significant differences in kinetics due to head
      end condition and anteroposterior eccentricity of the tensile load. The spine was
      then separated into motion segments for tension failure testing. The upper
      cervical spine tolerance of 2400 +/- 270 N (occiput-C2) was found to be
      significantly greater (p < 0.01) than the lower cervical spine tolerance of 1780
      +/- 230 N (C4-C5 and C6-C7 segments). Data from these experiments were used to
      develop and validate a computational model of the ligamentous spine. The model
      predicted the end condition and eccentricity responses for the tensile force
      displacement relationship. Cervical muscular geometry data derived from cadaver
      dissection and MRI imaging were used to incorporate a muscular response into the
      model. The cervical musculature under maximal stimulation increased the tolerance
      of the cervical spine from 1800 N to 4160 N. In addition, the cervical
      musculature resulted in a shift in the site of injury from the lower cervical
      spine to the upper cervical spine and offers an explanation for the mechanism of
      upper cervical spine tension injuries observed clinically. The results from this
      study predict a range in tensile tolerance from 1.8 - 4.2 kN based on the varying
      role of the cervical musculature.

PMID- 17458721
TI  - A Study of AIS1 Neck Injury Parameters in 168 Frontal Collisions Using a
      Restrained Hybrid III Dummy.
AB  - The research of AIS1 neck injuries has focused on rearend collisions, but a great
      portion of these injuries occur in frontal impacts. AIS1 neck injuries in frontal
      impacts can be associated with seat belt use and it can be hypothesized that the
      seat belt may transfer injurious loads to the neck. This study investigates the
      influence of the restraint system on the neck loads by using mechanical as well
      as mathematical (MADYMO) models of the HIII 50(th) percentile dummy. The
      mathematical simulations were based on 168 frontal crash pulses collected from
      crash recorders, installed in passenger cars in Sweden. The neck loads were
      evaluated by a new neck injury criterion NIC(protraction), the upper neck flexion
      moment and the Nij criterion. It was found that a pretensioner, a load limiter or
      an airbag have the potential to reduce the neck loads below recently suggested
      reference values for long-term neck injuries only as well as short- plus long
      term neck injuries. Moreover, the interaction between the pretensioner, the load
      limiter and the airbag was of great importance in order to minimize the neck
      loads.

PMID- 17458722
TI  - Influence of Airbags and Seatbelt Pretensioners on AIS1 Neck Injuries for Belted
      Occupants in Frontal Impacts.
AB  - AIS1 neck injuries are the most frequent disabling injuries among car occupants
      in road traffic accidents. Although neck injury is mostly regarded as resulting
      from rear end collisions, almost one third of all neck injuries occur in frontal
      impacts. Several studies have shown the effect of airbags on injury and fatality
      rates. However, studies of the effect of airbags on the risk of injuries to
      different body regions are rare. Airbags and seatbelt pretensioners may influence
      especially the risk of neck injuries. This paper presents influence of airbags
      and pretensioners on reported neck injury risk in frontal impacts. Cars fitted
      with airbags in combination with pretensioners and cars without have been
      analysed. Since 1992, approximately 150,000 vehicles on the Swedish market have
      been equipped with crash pulse recorders to measuring frontal impacts. This study
      includes results from 158 frontal impacts, where the crash pulses have been
      recorded using crash pulse recorders and where the status of airbag deployments
      was known. Only reported neck injuries, often denoted as short-term disability to
      the neck, were considered in this study. Injury risk functions for cars with and
      without airbags versus change of velocity and mean and peak accelerations were
      analysed. It was found that airbags in combination with seat belt pretensioners
      reduced the number of AIS1 neck injuries in frontal impacts with 41% +/- 15.2%.
      In impacts at a change of velocity between 1 and 30 km/h, airbags and
      pretensioners was found to reduce the neck injury risk with 59% +/- 18.6%.

PMID- 17458723
TI  - Investigation of Conditions that Affect Neck Compression- Flexion Injuries Using
      Numerical Techniques.
AB  - A Finite Element (FE) model of isolated head and neck complex was developed
      aiming to investigate the mechanisms of injury from axial impacts, in the
      sagittal plane, and the injury thresholds from experimental studies reported in
      the literature. The model was validated on a local and a global level, showing a
      significant correlation with experimental investigations and thereby having the
      potential to predict both reported injuries and dynamic buckling modes. The
      frequently reported Hangmans' fracture was predicted to occur at an axial load of
      about 3.5 kN and at a local injury threshold of 191 MPa in the compact bone of
      C2. Also, when analyzing an experimentally designed inner roof of a vehicle, the
      FE model showed that an induced anterior translation of the head reduced both
      stress and forces of the cervical spine bone. Moreover, the recent FE model
      suggests that combined compression/flexion may result in less severe injuries
      compared to pure compression or compression extension.

PMID- 17458724
TI  - Experimental and computational characterization of three-dimensional cervical
      spine flexibility.
AB  - Cervical spine behavior for generalized loading is often characterized using a
      full three-dimensional flexibility matrix. While experimental studies have been
      aimed at determining cervical motion segment behavior, their accuracy and utility
      have been limited both experimentally and analytically. For example, the
      nondiagonal terms, describing coupled motions, of the matrices have often been
      omitted. Flexibility terms have been primarily represented as constants despite
      the known nonlinear stiffening response of the spine. Moreover, there is
      presently no study validating the flexibility approach for predicting vertebral
      motions; nor have the effects of approximations and simplifications to the matrix
      representations been quantified. Yet, the flexibility matrix currently forms the
      basis for all multibody dynamics models of cervical spine motion. Therefore, the
      purpose of this study is to fully quantify the flexibility relationships for
      cervical motion segments, examine the diagonal and nondiagonal components of the
      flexibility matrix, and determine the extent to which multivariable relationships
      improve cervical spine motion prediction. To that end, using unembalmed human
      cervical spine motion segments, a full battery of flexibility tests were
      performed for a neutral orientation and also following an axial pretorque.
      Primary and coupled matrix components were described using linear and piecewise
      nonlinear incremental constants. An additional approach utilized multivariable
      incremental relationships to describe matrix terms. Measured motions were
      predicted using structural flexibility methods and were evaluated using RMS error
      of the difference between the predicted and measured responses. Results of this
      study provide a full set of flexibility relationships describing primary and
      coupled motions for C3-C4 and C5-C6 motion segment levels. Analysis of these data
      indicates that a flexibility matrix using incremental responses describing
      primary and coupled motions offers improved predictions over using linear methods
      (p<0.01). However, there is no significant improvement using more generalized
      nonlinear terms represented by the multivariable functional approach (p<0.2).
      Based on these findings, it is suggested that a multivariable approach for
      flexibility is more demanding experimentally and analytically while not offering
      improved motion prediction.

PMID- 17458725
TI  - Human Cervical Motion Segment Flexibility and Facet Capsular Ligament Strain
      under Combined Posterior Shear, Extension and Axial Compression.
AB  - The cervical facet capsular ligaments are thought to be an important anatomical
      site of whiplash injury, although the mechanism by which these structures may be
      injured during whiplash remains unclear. The purpose of this study was to
      quantify the intervertebral flexibility and maximum principal strain in the facet
      capsular ligament under combined shear, bending and compressive loads similar to
      those which occur during whiplash loading. Two motion segments (C3-4 and C5-6)
      from seven female donors (50 +/- 10 years) were exposed to quasi-static posterior
      shear loads of 135 N applied to the superior vertebra on four occasions while
      under compressive axial preloads of 0 N, 45 N, 197 N and 325 N. Vertebral body
      motions and the full Lagrangian strain field in the right facet capsular ligament
      were measured using stereophotogrammetry. After flexibility testing, the right
      facet joint of each motion segment was isolated and failed in posterior shear.
      Differences in the kinematic response of the vertebrae and maximum principal
      strain in the capsular ligaments under the four axial preloads were tested using
      repeated-measures ANOVA's for each load step. Although significant differences
      were observed at two axial load levels in the kinematic sequence (197 N and 325
      N), neither the regressed flexibility nor the maximum principal strain in the
      facet capsular ligament varied significantly with axial compression (p > 0.14).
      Maximum principal strain during the flexibility tests reached 61 +/- 33 percent
      of the maximum principal strain observed in sub-catastrophic failures of the
      isolated joints. Two of the thirteen specimens reached strains in their
      flexibility tests which were larger than their corresponding strains at sub
      catastrophic failure in the failure tests. These results suggest that the
      cervical facet capsular ligaments may be injured under combined shear, bending
      and compression load levels that occur in rear-end impacts.

PMID- 17458726
TI  - Kinematics of human cadaver cervical spine during low speed rear-end impacts.
AB  - The purposes of this study were to measure the relative linear and angular
      displacements of each pair of adjacent cervical vertebrae and to compute changes
      in distance between two adjacent facet joint landmarks during low posterior
      anterior (+Gx) acceleration without significant hyperextension of the head. A
      total of twentysix low speed rear-end impacts were conducted using six postmortem
      human specimens. Each cadaver was instrumented with two to three neck targets
      embedded in each cervical vertebra and nine accelerometers on the head.
      Sequential x-ray images were collected and analyzed. Two seatback orientations
      were studied. In the global coordinate system, the head, the cervical vertebrae,
      and the first or second thoracic vertebra (T1 or T2) were in extension during
      rear-end impacts. The head showed less extension in comparison with the cervical
      spine. Relative motion for each cervical motion segment went from flexion at the
      upper cervical levels to extension at the lower cervical levels, with a
      transition region at the mid-cervical levels. This rotational pattern formed an
      "S" shape in the cervical spine during the initial phase of low-speed rear
      impacts. A pair of facet joint landmarks on each cervical motion segment was used
      to measure the distance across the joint space. Uni-axial facet capsular strains
      were calculated by dividing changes in this distance over the original distance
      in seven tests using three specimens. In 20-degree seatback tests, the average
      strain was 32+/-11% for the C2/C3 facet joint (17%-43% range), and 59+/-26% for
      the C3/C4 facet joint (41%-97% range). The C4/C5 and C5/C6 facet joints exhibited
      peak tensile or compressive strains in different specimens. In 0-degree seatback
      tests, the average strain was 28+/-11% for the C2/C3 facet joint (21%-41% range),
      30+/-9% for the C3/C4 facet joint (21%-39% range), 22+/-4% for the C4/C5 facet
      joint (19%-25% range), and 60+/-13% for the C5/C6 facet joint (51%-69% range). In
      20-degree seatback tests, there was less initial cervical lordosis, more upward
      ramping of the thoracic spine, and more relative rotation of each cervical motion
      segment in comparison with the 0-degree seatback tests. Relative to T1, the head
      went from flexion to extension for 20-degree seatback tests while stayed in
      extension for 0-degree seatback tests.

PMID- 17458727
TI  - Biomechanics of human occupants in simulated rear crashes: documentation of neck
      injuries and comparison of injury criteria.
AB  - The objective of this study was to subject small female and large male cadavers
      to simulated rear impact, document soft-tissue injuries to the neck, determine
      the kinematics, forces and moments at the occipital condyles, and evaluate neck
      injury risks using peak force, peak tension and normalized tension-extension
      criteria. Five unembalmed intact human cadavers (four small females and one large
      male) were prepared using accelerometers and targets at the head, T1, iliac
      crest, and sacrum. The specimens were placed on a custom-designed seat without
      head restraint and subjected to rear impact using sled equipment. High-speed
      cameras were used for kinematic coverage. After the test, x-rays were obtained,
      computed tomography scans were taken, and anatomical sections were obtained using
      a cryomicrotome. Two female specimens were tested at 4.3 m/s (mean) and the other
      two were tested at 6.8 m/s (mean), and one large male specimen was subjected to
      6.6 m/s velocity. One female specimen tested at 4.1 m/s did not sustain injury.
      All others produced injuries to soft tissue and joint-related structures that
      included tearing of the anterior longitudinal ligament, rupture of the ligamentum
      flavum, hematoma at the upper facet joint, anterior disc disruption at the lower
      spine, and facet joint capsule tear. Compressive forces (100 to 254 N) developed
      within 60 ms after impact. Tensile forces were higher (369 to 904) and developed
      later (149 to 211 ms). While peak shear forces (268 to 397 at 4.3 m/s and 257 to
      525 N at 6.8 m/s) did not depend on velocity, peak tensile forces (369 to 391 N
      at 4.3 m/s and 672 to 904 N at 6.8 m/s) seemed to correlate with velocity. Peak
      extension moments ranged from 22.0 to 33.5 Nm at low velocity and 32.7 to 46.6 Nm
      at high velocity. All these biomechanical data attained their peaks in the
      extension phase (with very few exceptions), which ranged from 179 to 216 ms. The
      neck injury criterion, NIC, exceeded the suggested limit of 15 m(2)/s(2) in all
      specimens. Axial force and bending moment data were used to evaluate various neck
      injury criteria (N(ij), N(TE), peak tension and peak extension). The risk for AIS
      >/= 3 injury for the combined tension-extension criteria was 30 percent in one
      female specimen tested at 6.8 m/s. For the other specimens the risk of AIS >/= 3
      injury was less than five percent using all criteria.

PMID- 17458728
TI  - Defining brain mechanical properties: effects of region, direction, and species.
AB  - No regional or directional large-deformation constitutive data for brain exist in
      the current literature. To address this deficiency, the large strain (up to 50%)
      directional properties of gray and white matter were determined in the thalamus,
      corona radiata, and corpus callosum. The constitutive relationships of all
      regions and directions are well fit by an Ogden hyperelastic relationship,
      modified to include dissipation. The material parameter alpha, representing the
      non-linearity of the tissue, was not significantly sensitive to region,
      direction, or species. The average value of the material parameter mu,
      corresponding to the shear modulus of the tissue, was significantly different for
      each region, demonstrating that brain tissue is inhomogeneous. In each region,
      mu, obtained in 2 orthogonal directions, was compared. Consistent with local
      neuroarchitecture, gray matter showed the least amount of anisotropy and corpus
      callosum exhibited the greatest degree of anisotropy. Finally, human temporal
      lobe gray matter properties were determined and compared to porcine thalamic
      properties. The results show significant regional inhomogeneity at large strains
      and significant anisotropy in each region tested. The extent of regional
      anisotropy correlated with the degree of alignment in the local
      neuroarchitecture. These large strain, regional and directional data should
      enhance the biofidelity of computational models and provide important information
      regarding the mechanisms of traumatic brain injury.

PMID- 17458729
TI  - A proposed new biomechanical head injury assessment function - the maximum power
      index.
AB  - Recently, several cases of mild traumatic brain injury to American professional
      football players have been reconstructed using instrumented Hybrid III
      anthropomorphic test dummies ATDs. The translational and rotational acceleration
      responses of injured and uninjured players' heads have been documented. The
      acceleration data have been processed according to all current head injury
      assessment functions including the GSI, HIC and GAMBIT among others. A new
      hypothesis is propounded that the threshold for head injury will be exceeded if
      the rate of change of kinetic energy of the head exceeds some limiting value. A
      functional relation is proposed, which includes all six degrees of motion and
      directional sensitivity characteristics, relating the rate of change of kinetic
      energy to the probability of head injury. The maximum value that the function
      achieves during impact is the maximum power input to the head and serves as an
      index by which the probability of head injury can be assessed.

PMID- 17458730
TI  - The large shear strain dynamic behaviour of in-vitro porcine brain tissue and a
      silicone gel model material.
AB  - The large strain dynamic behaviour of brain tissue and silicone gel, a brain
      substitute material used in mechanical head models, was compared. The non-linear
      shear strain behaviour was characterised using stress relaxation experiments.
      Brain tissue showed significant shear softening for strains above 1%
      (approximately 30% softening for shear strains up to 20%) while the time
      relaxation behaviour was nearly strain independent. Silicone gel behaved as a
      linear viscoelastic solid for all strains tested (up to 50%) and frequencies up
      to 461 Hz. As a result, the large strain time dependent behaviour of both
      materials could be derived for frequencies up to 1000 Hz from small strain
      oscillatory experiments and application of Time Temperature Superpositioning. It
      was concluded that silicone gel material parameters are in the same range as
      those of brain tissue. Nevertheless the brain tissue response will not be
      captured exactly due to increased viscous damping at high frequencies and the
      absence of shear softening in the silicone gel. For trend studies and
      benchmarking of numerical models the gel can be a good model material.

PMID- 17458731
TI  - Shoulder response characteristics and injury due to lateral glenohumeral joint
      impacts.
AB  - The objective of this study was to determine response characteristics and injury
      of the shoulder due to lateral impacts. The need for this data was heightened in
      the 1990s with increasing interest in harmonization of side impact standards, and
      questions regarding the measurement capabilities of dummies used in evaluating
      side impacts. A pneumatic impacting ram was employed in carrying out twentytwo
      lateral impacts to eleven unembalmed human cadavers at the level of the
      glenohumeral joint. Velocity of the ram at the time of impact was varied
      throughout the impacts from 3.5 to 7.0 m/sec, in an attempt to determine injury
      threshold. The cadavers were instrumented with tri-axial accelerometer blocks at
      ten locations in the shoulder region. Bony structures instrumented included the
      sternum, the first thoracic vertebra (T1), clavicles and scapulae. Output from
      the accelerometers was utilized to calculate impact forces and to exa mine the
      movement of the instrumented structures. Photographic target pins were inserted
      into the accelerometer blocks, thus permitting image analysis of the shoulder
      girdle displacement. Autopsies, radiographs, and magnetic resonance images (MRIs)
      were performed to document trauma that occurred as a result of the impact to the
      shoulder. Clavicles from the cadavers were subjected to bone density scans and
      threepoint bending tests. Results from these evaluations were used to assess and
      compare properties of bones of the upper extremities. Observations from autopsy,
      MRI, and radiography have shown looseness of the sternoclavicular joint and
      fracture of the distal clavicle to be the most common injuries. Significant
      findings include normalized shoulder forcedeflection curves and probability of
      injury distribution.

PMID- 17458732
TI  - Development of a finite element model of the human shoulder.
AB  - Previous studies have hypothesized that the shoulder may be used to absorb some
      impact energy and reduce chest injury due to side impacts. Before this hypothesis
      can be tested, a good understanding of the injury mechanisms and the kinematics
      of the shoulder is critical for occupant protection in side impact. However,
      existing crash dummies and numerical models are not designed to reproduce the
      kinematics and kinetics of the human shoulder. The purpose of this study was to
      develop a finite element model of the human shoulder in order to achieve a deeper
      understanding of the injury mechanisms and the kinematics of the shoulder in side
      impact. Basic anthropometric data of the human shoulder used to develop the
      skeletal and muscular portions of this model were taken from commercial data
      packages. The shoulder model included three bones (the humerus, scapula and
      clavicle) and major ligaments and muscles around the shoulder. This model was
      then integrated into a human thorax model developed at Wayne State University
      (WSU) along with pre-existing models of other body parts such as the pelvis and
      the lower extremities. Material properties used for the model were taken from the
      literature. The model was first used to simulate lateral shoulder impact study by
      the Association Peugeot- Renault (APR) followed by simulations of several of the
      17 rigid and padded cadaveric impacts conducted on a side impact sled at WSU.
      Contact forces measured at the levels of shoulder, thorax, abdomen and pelvis
      were used as response variables to validate the model. Additionally, a cadaveric
      test involving the deployment of a generic side airbag was also used to check the
      validity of the model. Model prediction of accelerations of the shoulder matched
      well against those measured experimentally. The role of the shoulder in side
      impact protection and the reduction of injury to the ribcage are discussed, based
      on model results.

PMID- 17458733
TI  - The effect of loading rate on the degree of acute injury and chronic conditions
      in the knee after blunt impact.
AB  - accidents are often overlooked, but can have a profound societal cost. Knee
      injuries, for example, account for approximately 10% of the total injuries.
      Fracture of the knee is not only an acute issue but may also have chronic, or
      long term, consequences. The criterion currently used for evaluation of knee
      injuries in new automobiles, however, is based on experimental impact data from
      the 70's using seated human cadavers. These studies involved various padded and
      rigid impact interfaces that slightly alter the duration of contact. Based on
      these data and a simple mathematical model of the femur, it appears fracture
      tolerance increases as contact duration shortens. In contrast, more recent
      studies have shown mitigation of gross fractures of the knee itself using padded
      interfaces. The use of padded interfaces, however, result in coincidental changes
      in contact duration and knee contact area. Therefore, it is difficult to extract
      the direct effect of loading rate on fracture tolerance of the knee. The object
      of the current study was to isolate the effect of loading rate alone on fracture
      tolerance of the human knee joint. Paired experiments were conducted on eight
      pairs of isolated cadaver knees impacted with a rigid interface to approximately
      5 kN at a high (5 ms to peak) or low (50 ms to peak) rate of loading. Gross
      fracture and occult microfractures of the knee joint were documented. A second
      part of the study examined some chronic effects of loading rate on "subfracture"
      injuries in an animal. Thirty-four rabbits were subjected to a "subfracture" knee
      load at the same rates as used in the human studies. Alterations in the
      mechanical properties of retropatellar cartilage and thickening of subchondral
      bone were documented out to one year post "subfracture" trauma to the joint. The
      current study documented an opposite effect than that expected based on 70's
      experiments with seated cadavers. There was an increase in the number of gross
      fractures and occult microfractures in high versus low rate of loading
      experiments. A similar effect was also seen in the "subfracture" chronic animal
      experiments, which showed relatively more degradative change in the mechanical
      properties of cartilage following high versus low rate of loading experiments.
      There was also a significant increase in subchondral bone thickening underlying
      cartilage and increased fissuring of cartilage in high versus low rate of loading
      experiments. The current study suggests a relative decrease in tolerance of the
      knee at high versus low rates of loading in acute experiments with human cadavers
      and in the chronic setting with animals. Therefore, it would appear that rate of
      knee loading may be an important issue in establishing a future injury criterion
      for the knee itself.

PMID- 17458734
TI  - Development and validation of a pedestrian lower limb non-linear 3-d finite
      element model.
AB  - Lower limb injury is becoming an increasingly important concern in vehicle safety
      for both occupants and pedestrians. To enable vehicle manufacturers to better
      understand the biomechanical effects of design changes, it is deemed beneficial
      to employ a biomechanically fidelic finite element model of the human lower limb.
      The model developed in this study includes long bones (tibia, fibula, femur) and
      flat bone (patella) as deformable bodies. The pelvis and foot bones are modeled
      as rigid bodies connected to the femur and tibia/fibula via rotational spring
      dashpots. The knee is defined by scanned bone surface geometry and is surrounded
      by the menisci, major ligaments, and patellar tendon. Finite elements used to
      model include 6- and 8-node solids for cartilage, menisci, surrounding muscles,
      and cancellous bone; 3- and 4-node shells for skin and cortical bone; and
      nonlinear spring-dashpots for ligaments. Anatomical, physiological, and material
      properties data are from the literature while the bone surface geometry was
      scanned by a commercial source. Validation against published cadaver test results
      consisted of tibia and femur 3-point bending (lateralmedial and anterior
      posterior) and whole limb lateral knee shear. Validation was performed under both
      static and dynamic loading conditions, until bone failure or ligament rupture.
      Additional dynamic validation with the lower limb in a seated orientation has not
      been completed, limiting current applications to the pedestrian impact condition.
      The validated models were employed to examine the effect of axial compressive
      force (the physiological condition) on tibia and femur lateral-medial and
      anterior-posterior bending under static conditions.

PMID- 17458735
TI  - Development and validation of the finite element model for the human lower limb
      of pedestrians.
AB  - An impact test procedure with a legform addressing lower limb injuries in car
      pedestrian accidents has been proposed by EEVC/WG17. Although a high frequency of
      lower limb fractures is observed in recent accident data, this test procedure
      assesses knee injuries with a focus on trauma to the ligamentous structures. The
      goal of this study is to establish a methodology to understand injury mechanisms
      of both ligamentous damages and bone fractures in car-pedestrian accidents. A
      finite element (FE) model of the human lower limb was developed using PAM
      CRASH(TM). The commercially available H-Dummy(TM) lower limb model developed by
      Nihon ESI for a seated position was modified to represent the standing posture of
      pedestrians. Mechanical properties for both bony structures and knee ligaments
      were determined from our extensive literature survey, and were carefully
      implemented in the model considering their strain rate dependency in order to
      simulate the dynamic response of the lower limb accurately. The element
      elimination option in PAMCRASH(TM) was used to simulate both bone fractures and
      ligamentous ruptures. Bone models were validated against test results obtained
      from literature in both static and dynamic conditions. The dynamic response of
      the knee joint was validated against the response corridors from a series of
      experiments with Post-Mortem Human Subject (PMHS) presented in the literature. In
      addition, the lower limb model was validated against published experiments with
      isolated lower limbs subjected to lateral impact simulating car-pedestrian
      accidents. The validated FE lower limb model was integrated with an upper body
      model with rigid segments to obtain a fullbody pedestrian model. Computer
      simulations using both the pedestrian model and a FE model for the car front were
      conducted to reconstruct a published carpedestrian impact test with PMHS. Leg
      fracture observed in the experiment was reproduced from the FE carpedestrian
      model. The developed FE model can be used as an effective tool to investigate
      injury mechanisms of the lower limb in car-pedestrian accidents.

PMID- 17458736
TI  - Biomechanics of ankle and hindfoot injuries in dynamic axial loading.
AB  - Twenty-three Post Mortem Human Surrogate (PMHS) limbs were impacted using a test
      set up that was developed to simulate the loading conditions seen in a frontal
      collision. Articulation studies were performed on each limb prior to impact.
      Failure occurred at impact loads of 5.7+/-1.9 kN (resultant tibial failure load
      6.4+/-1.9 kN) and the following injuries were generated: 9 intra-articular
      calcaneal fractures; 1 talar neck and 2 talar body fracture; 3 intra-articular
      distal tibial (pilon) fractures; 2 malleolar fractures; 3 soft tissue injuries
      and 3 had no detectable injury. The impact test conditions were replicated with a
      Hybrid III leg in a first attempt at developing injury risk functions for the
      dummy. This study has demonstrated the significance of preload through muscle
      tension and the intrinsic properties of PMHS specimens in the generation of
      severe ankle and hindfoot injury.

PMID- 17458737
TI  - Project MX-981: John Paul Stapp and Deceleration Research.
AB  - Project MX-981, Effects of Deceleration Forces of High Magnitude on Man, was
      initiated in 1945 by the U.S. Army Air Force Aero Medical Laboratory at Wright
      Field, Ohio to confirm the feasibility of a "40 g" crash restraint system for
      pilots of military aircraft. Captain John Paul Stapp, MD, was selected to carry
      out this work. This paper provides historical background and perspective for that
      project, and summarizes Dr. Stapp's work on that Project at Edwards AFB,
      California, and his subsequent tests at Holloman AFB, New Mexico.

PMID- 17458738
TI  - Abdominal impact response to rigid-bar, seatbelt, and airbag loading.
AB  - This study was conducted to resolve discrepancies and fill in gaps in the
      biomechanical impact response of the human abdomen to frontal impact loading.
      Three types of abdominal loading were studied: rigid-bar impacts, seatbelt
      loading, and close-proximity (out-of-position) airbag deployments. Eleven rigid
      bar free-back tests were performed into the mid and upper abdomens of unembalmed
      instrumented human cadavers using nominal impact speeds of 6 and 9 m/s. Seven
      fixed-back rigid-bar tests were also conducted at 3, 6, and 9 m/s using one
      cadaver to examine the effects of body mass, spinal flexion, and repeated
      testing. Load-penetration corridors were developed and compared to those
      previously established by other researchers. Six seatbelt tests were conducted
      using three cadavers and a peak-loading rate of 3 m/s. The seatbelt loading tests
      were designed to maximize belt/abdomen interaction and were not necessarily
      representative of real-world crashes. The results were compared to data
      previously obtained by other researchers using swine and were used to establish a
      new abdominal load-penetration corridor for belt loading. Passenger frontal
      airbags were deployed into the closely positioned abdomen of three unembalmed
      cadavers. The penetration-time histories were used to guide the development of a
      repeatable high-speed surrogate airbag-loading device that uses a low-mass
      cylinder to simulate the initial breakout phase of close-proximity passenger
      airbag loading of the abdomen. This device was used to conduct simulated out-of
      position airbag tests into three cadaver abdomens. The abdomen response data from
      these standardized tests were used to develop a load-penetration corridor for
      abdomen response to out-of-position airbag deployments.

PMID- 17458739
TI  - Development of a Reusable, Rate-Sensitive Abdomen for the Hybrid III Family of
      Dummies.
AB  - The objective of this work was to develop a reusable, rate-sensitive dummy
      abdomen with abdominal injury assessment capability. The primary goal for the
      abdomen developed was to have good biofidelity in a variety of loading situations
      that might be encountered in an automotive collision. This paper presents a
      review of previous designs for crash dummy abdomens, a description of the
      development of the new abdomen, results of testing with the new abdomen and
      instrumentation, and suggestions for future work. The biomechanical response
      targets for the new abdomen were determined from tests of the mid abdomen done in
      a companion biomechanical study. The response of the abdominal insert is an
      aggregate response of the dummy's entire abdominal area and does not address
      differences in upper versus lower abdominal response, solid versus hollow organs,
      or organ position or mobility. While the abdomen developed has demonstrated good
      biofidelity in rigid bar, seat belt and airbag loading situations, some work
      remains to be done before it can be used in crash testing.

PMID- 17458740
TI  - Development and Testing of a Prototype Pregnant Abdomen for the Small-Female
      Hybrid III ATD.
AB  - A new prototype pregnant abdomen for the Hybrid III small-female ATD is being
      developed and has been evaluated in a series of component and whole-dummy tests.
      The new abdomen uses a fluid-filled silicone-rubber bladder to represent the
      human uterus at 30-weeks gestation, and incorporates anthropometry based on
      measurements of pregnant women in an automotive driving posture. The response of
      the new pregnant abdomen to rigid-bar, belt, and close-proximity airbag loading
      closely matches the human cadaver response, which is thought to be representative
      to the response of the pregnant abdomen. In the current prototype, known as MAMA
      2B (Maternal Anthropomorphic Measurement Apparatus, version 2B), the risk of
      adverse fetal outcome is determined by measuring the peak anterior pressure
      within the fluid-filled bladder. Peak internal bladder pressures measured in a
      series of sled-test simulations of frontal crashes of different severities and
      occupant-restraint conditions have been correlated to the likelihood of adverse
      fetal outcome based on risk curves developed from in-depth investigations of real
      world crashes involving pregnant occupants. Compared to the original pregnant
      abdomen, the new prototype has improved geometry and improved impact response to
      a range of potential in-vehicle loading conditions, However, additional
      instrumentation development and more rigorous testing are needed before the MAMA
      2B can be confidently used to assess restraint system performance with regard to
      reducing the likelihood of adverse fetal outcome in motor-vehicle crashes.

PMID- 17458741
TI  - Development of a finite element model of the human abdomen.
AB  - Currently, three-dimensional finite element models of the human body have been
      developed for frequently injured anatomical regions such as the brain, chest,
      extremities and pelvis. While a few models of the human body include the abdomen,
      these models have tended to oversimplify the complexity of the abdominal region.
      As the first step in understanding abdominal injuries via numerical methods, a 3D
      finite element model of a 50(th) percentile male human abdomen (WSUHAM) has been
      developed and validated against experimental data obtained from two sets of side
      impact tests and a series of frontal impact tests. The model includes a detailed
      representation of the liver, spleen, kidneys, spine, skin and major blood
      vessels. Hollow organs, such as the esophagus, stomach, small and large
      intestines, gallbladder, bile ducts, ureters, rectum and adrenal glands are
      grouped into three bodybags in order to provide realistic inertial properties and
      to maintain the position of the solid organs in their appropriate locations.
      Using direct connections, the model was joined superiorly to a partial model of
      the human thorax, and inferiorly to models of the human pelvis and the lower
      extremities that have been previously developed. Material properties for various
      tissues of the abdomen were derived from the literature. Data obtained in a
      series of cadaveric pendulum impact tests conducted at Wayne State University
      (WSU), a series of lateral drop tests conducted at Association Peugeot-Renault
      (APR) and a series of cadaveric lower abdomen frontal impact tests conducted at
      WSU were used to validate the model. Results predicted by the model match these
      experimental data for various impact speeds, impactor masses and drop heights.
      Further study is still needed in order to fully validate WSUHAM before it can be
      used to assess various impact loading conditions associated with vehicular
      crashes.

PMID- 17458742
TI  - Injury and response of the shoulder in lateral sled tests.
AB  - The biomechanical response and injury tolerance of the shoulder in lateral
      impacts is not well understood. These data are needed to better understand human
      injury tolerance, validate finite element models and develop biofidelic shoulders
      in side impact dummies. Seventeen side impact sled tests were performed with
      unembalmed human cadavers. Data analyzed for this study include T1-Y
      acceleration, shoulder and thoracic load plate forces, upper sternum x and y
      accelerations, and struck side acromion x, y and z accelerations. One dimensional
      deflection at the shoulder level was determined from high-speed film by measuring
      the distance between a target on T1 and the impacted wall. Force-time response
      corridors were obtained for tests with 9 m/s pelvic offset, 10.5 m/s pelvic
      offset, 9 m/s unpadded flat wall, 6.7 m/s unpadded flat wall, 9 m/s soft padding
      and 9 m/s stiff padding. Maximum shoulder plate forces in unpadded 9 m/s tests
      (5.5 kN) were larger than in 6.7 m/s tests (3.3 kN). The peak force at the
      shoulder was larger than at the thorax plate in unpadded and soft padded tests.
      T1-Y accelerations were larger in unpadded 9 m/s flat wall tests and unpadded
      pelvic offset 10.5 m/s tests (peak values of 130 and 145 g's) than in other test
      conditions. Deflections between T1 and the struck wall ranged from 88 to 154 mm
      in unpadded tests and 95 to 128 mm in stiff and soft padded tests. Eighteen AIS 2
      level shoulder injuries occurred in 11 test subjects. These injuries included
      left acromion fracture in five subjects, left acromioclavicular separation in ten
      subjects and left clavicle fracture in three subjects. Average MAIS to the
      shoulder was 0.86 in seven subjects which impacted 4 to 6 inches (101.6 to 152.4
      mm) of soft or stiff padding and 1.6 in ten subjects which impacted no padding or
      3 inches (76.2 mm) of stiff padding. Previous findings from this test series were
      reported by Irwin et al. (1993) for seven tests and focused on detailed analysis
      of shoulder deflection (T5 to shoulder edge). The current study is expanded to 17
      tests and includes force, acceleration response and analysis of shoulder
      deflection (T1 to shoulder edge). Padding of 4 to 6 inches (101.6 mm to 152.4 mm)
      reduced shoulder injury approximately one AIS level. A combination of ASA10 and
      deflection was the best shoulder injury predictor. Shoulder deflection of 106 mm
      predicts 50% probability of MAIS 2.

PMID- 17458743
TI  - Material properties for modeling traumatic aortic rupture.
AB  - Traumatic aortic rupture is a significant cause of fatalities in frontal
      automobile crashes. However, such ruptures are difficult to reproduce
      experimentally in cadaveric surrogates, and it is difficult to observe dynamic
      aortic response in situ. So, the aortic injury mechanism or mechanisms remains in
      dispute. This study is a staged investigation of the physical parameters and
      mechanisms of human aortic rupture. The investigation includes both experimental
      study of local and global viscoelastic properties and failure properties of
      aortas using aortic tissue samples, excised aortas in vitro, and whole human
      aortas in situ in cadaver thoraxes. This study is the first phase in a staged
      programme to develop a finite element computer model of aorta injury to examine
      the mechanisms of aorta injury in automobile crashes. The high-rate local biaxial
      properties of porcine aorta tissue are determined from samples taken from the
      isthmus region, the most common area of failure in traumatic aorta injury. Using
      porcine aortas, similar in structure and physical characteristics to human aortic
      tissue, biaxial oscillatory response is determined at large strains and high
      strain rates. From this data, a hyperelastic material model with a failure
      threshold is developed that is in good agreement with local property data
      determined from oscillatory tests at 20 Hz and 65 Hz. Further, whole aorta tests
      are performed using pressure application with aortic pressure time histories
      similar in onset rate to those seen in cadaveric sled testing. These tests
      establish the ultimate stretch ratio and strain to failure for human aorta
      specimens. The specimens show no significant difference in response between the
      in situ tests and the in vitro tests. This indicates either that the internal
      thoracic boundary conditions may not be important in the stress and strain level
      of aorta failure or that the number of in situ tests (3) was too small to
      establish a difference. A Weibull survival analysis of the whole aorta failure
      tests shows significant dependence of aortic ultimate stretch ratio on age. A 50%
      risk of failure is 852 kPa in the circumferential direction and 426 kPa in the
      longitudinal direction. For pressure, the 50% risk of failure for all the tests
      is approximately 101 kPa. This increases to greater than 120 kPa for subjects
      below 68 years.

PMID- 17458744
TI  - Development of a computer model to predict aortic rupture due to impact loading.
AB  - Aortic injuries during blunt thoracic impacts can lead to life threatening
      hemorrhagic shock and potential exsanguination. Experimental approaches designed
      to study the mechanism of aortic rupture such as the testing of cadavers is not
      only expensive and time consuming, but has also been relatively unsuccessful. The
      objective of this study was to develop a computer model and to use it to predict
      modes of loading that are most likely to produce aortic ruptures. Previously, a
      3D finite element model of the human thorax was developed and validated against
      data obtained from lateral pendulum tests. The model included a detailed
      description of the heart, lungs, rib cage, sternum, spine, diaphragm, major blood
      vessels and intercostal muscles. However, the aorta was modeled as a hollow tube
      using shell elements with no fluid within, and its material properties were
      assumed to be linear and isotropic. In this study fluid elements representing
      blood have been incorporated into the model in order to simulate pressure changes
      inside the aorta due to impact. The current model was globally validated against
      experimental data published in the literature for both frontal and lateral
      pendulum impact tests. Simulations of the validated model for thoracic impacts
      from a number of directions indicate that the ligamentum arteriosum, subclavian
      artery, parietal pleura and pressure changes within the aorta are factors that
      could influence aortic rupture. The model suggests that a right-sided impact to
      the chest is potentially more hazardous with respect to aortic rupture than any
      other impact direction simulated in this study. The aortic isthmus was the most
      likely site of aortic rupture regardless of impact direction. The reader is
      cautioned that this model could only be validated on a global scale. Validation
      of the kinematics and dynamics of the aorta at the local level could not be done
      due to a lack of experimental data. It is hoped that this model will be used to
      design experiments that can reproduce field relevant aortic ruptures in the
      laboratory. Only after such experiments have been run, can local validation be
      examined and the model judged to be acceptable or unacceptable.

PMID- 17458745
TI  - The influence of superficial soft tissues and restraint condition on thoracic
      skeletal injury prediction.
AB  - The purpose of this study is to evaluate the hard tissue injury-predictive value
      of various thoracic injury criteria when the restraint conditions are varied. Ten
      right-front passenger human cadaver sled tests are presented, all of which were
      performed at 48 km/h with nominally identical sled deceleration pulses. Restraint
      conditions evaluated are 1) force-limiting belt and depowered airbag (4 tests),
      2) non-depowered airbag with no torso belt (3 tests), and 3) standard belt and
      depowered airbag (3 tests). Externally measured chest compression is shown to
      correspond well with the presence of hard tissue injury, regardless of restraint
      condition, and rib fracture onset is found to occur at approximately 25% chest
      compression. Peak acceleration and the average spinal acceleration measured at
      the first and eighth or ninth thoracic vertebrae are shown to be unrelated to the
      presence of injury, though clear variations in peaks and time histories among
      restraint conditions can be seen. The maximum viscous criterion is found to
      correspond with injury, but only because it increases with the maximum chest
      compression. A simple analytical study is presented to elucidate the observed
      restraint condition dependence of rib fracture location and the restraint
      insensitivity of injurious maximum chest compression. Computed tomography images
      of a loaded torso are presented to show the load-distributing effect of the soft
      tissues superficial to the rib cage.

PMID- 17458746
TI  - Comparison of Thoracic Injury Risk in Frontal Car Crashes for Occupant Restrained
      without Belt Load Limiters and Those Restrained with 6 kN and 4 kN Belt Load
      Limiters.
AB  - In France, as in other countries, accident research studies show that a large
      proportion of restrained occupants who sustain severe or fatal injuries are
      involved in frontal impacts (65% and 50%, respectively). In severe frontal
      impacts with restrained occupants and where intrusion is not preponderant, the
      oldest occupants very often sustain severe thoracic injuries due to the
      conventional seat belt. As we have been observing over the last years, we will
      expect in the coming years developments which include more solidly-built cars, as
      offset crash test procedures are widely used to evaluate the passive safety of
      production vehicles. The reduction of intrusion for the most severe frontal
      impacts, through optimization of car deformation, usually translates into an
      increase in restraint forces and hence thoracic injury risk with a conventional
      retractor seat belt for a given impact severity. It is, therefore essential to
      limit the restraint forces exerted by the seat belt on the thorax in order to
      reduce the number of road casualties. In order to address thoracic injury risk in
      frontal impact, Renault cars have been equipped with the Programmed Restraint
      System (PRS) since 1995. The PRS is a restraint system that combines belt load
      limitation and pyrotechnic belt pretension. In an initial design of the
      Programmed Restraint System (PRS1), the belt load limiter was a steel component
      designed to shear at a given shoulder force, namely 6 kN. It was mounted between
      the retractor and the lower anchorage point of the belt. The design of the PRS
      was modified in 1998 (PRS2), but the principle of load limitation was maintained.
      The threshold was decreased to 4 kN and this lower belt belt-force limiter has
      been combined with a specially designed airbag. This paper reports on 347 real
      world frontal accidents where the EES (Equivalent Energy Speed) ranged from 35 to
      75 km/h. One hundred and ninety-eight (198) of these accidents involved cars
      equipped with the 6 kN load limiter, and 149 involved cars equipped with the 4 kN
      load limiter. Based on this accident data, the study compares the thoracic injury
      risk for two occupant populations: belted occupants involved in accidents in
      which the vehicle was not equipped with a load limiter (378 cases with
      pyrotechnic pretensioners), and belted occupants involved in accidents in which
      the vehicles were equipped with 4 or 6 kN load limiters and pyrotechnic
      pretensioners (347 cases). One observes that a 4 kN load limitation results in a
      very important reduction of thoracic injury risk for all AIS levels, compared to
      others samples. 50 to 60% reduction for AIS 2+ was observed, as well as 75 to 85%
      for AIS 3+. The complete absence of AIS 4+ with a 4 kN load limiter must be
      stressed, though it remains more than 8% for the other samples (no limiter and 6
      kN limiter).

PMID- 17458747
TI  - Development and Evaluation of a New Rear-Impact Crash Dummy: The RID 2.
AB  - Low severity neck injuries due to vehicle accidents are a serious problem in our
      society. In 1997 the European Whiplash project started with the aim to develop
      passive safety methodologies to reduce the frequency of neck injuries in rear-end
      impacts. This project has resulted, among others, in a rear impact crash dummy,
      the so-called RID2. The objective of this paper is present the design of this
      dummy and to present its performance in comparison with human volunteer and post
      mortem human subject (PMHS) tests. Also a comparison is made with the Hybrid III
      dummy in similar test conditions. In the comparison with human volunteers in a
      real car seat, both the RID2 and the Hybrid III showed realistic kinematics.
      Lower neck rotation as well as the typical S-shape in the neck were found in the
      RID2, but not in the Hybrid III dummy. Ramping up was not found in the Hybrid
      III, while the RID2 did show limited ramping up. The upper neck forces measured
      in both dummies were reasonably good in the regular car seat, but upper neck
      torques were not well predicted in either dummy. Compared to post mortem human
      subjects placed on a rigid seat without a head restraint, the Hybrid III was
      found to be less biofidelic than the RID2, as the kinematics of the human
      subjects were better approximated by the RID2 than by the Hybrid III, which was
      mainly attributed to the stiff spine and neck of the Hybrid III.

PMID- 17458748
TI  - Kinetic and Kinematic Responses of the RID2a, Hybrid III and Human Volunteers in
      Low-Speed Rear-End Collisions.
AB  - An anthropomorphic test device (ATD) which accurately models the kinematic and
      kinetic responses of human subjects during head restraint contact in low-speed
      rear-end collisions is needed to evaluate present and future seat and vehicle
      designs. The primary goal of this study was to quantify the biofidelity of a new
      rear-impact ATD, the RID2a, by comparing its dynamic response to those of human
      subjects under identical test conditions. For this study, a RID2a and a Hybrid
      III ATD were each exposed to 10 low-speed rear-end collisions: five at a speed
      change of 4 km/h and five at a speed change of 8 km/h. Sagittal plane kinematics
      of the head and upper torso, head restraint contact forces, and the reaction
      loads and moment at the atlanto-occipital joint were determined and compared to
      the response of eleven male human subjects. Both ATDs produced repeatable
      response corridors. As observed by others, the Hybrid III did not replicate many
      features of the human response. Aside from the vertical response of the head and
      T1 in the global reference frame, the kinematic and kinetic responses of the
      RID2a reproduced most features of the human response. Head restraint forces
      observed in both the human subjects and the RID2a contained large vertical
      components that placed the neck in tension during head restraint contact. The
      results of this study indicated that the RID2a was able to model the overall
      kinematic and kinetic responses relevant to some recently-proposed mechanisms of
      whiplash injury.

PMID- 17458749
TI  - A Comparison of the Hybrid III and BioRID II Dummies in Low-Severity, Rear-Impact
      Sled Tests.
AB  - A BioRID II dummy and a Hybrid III dummy, each representative of a midsize adult
      male, were tested side-by-side in simulated rear-impact sled tests. In all tests
      the dummies were restrained by 3-point belt systems. The results of 4 test sets
      conducted at a nominal change in velocity (deltaV) of 16 km/hr are presented and
      discussed. In three of the test sets, bucket seats were used. The head restraints
      were placed in the up-position in two of the three test sets and in the down
      position in the third set of tests. In the fourth test set, rigid seats without
      any head restraints were used. While analyzing the BioRID II data, the presence
      of an axial neck load acting on the head, which bypassed the upper neck load
      transducer, was discovered in all the reported tests. The implication of this
      observation is that the axial force and all the moments measured by the BioRID II
      upper neck load transducer could be erroneous. A second concern with the BioRID
      II data was the high frequency noise observed, especially on the T1 acceleration
      response which is used in the NIC calculation. The 18 Hz filter used to process
      the T1 acceleration data for the NIC calculation attenuated the peak NIC values
      by 15% as compared to the SAE 180 filtered values. The unmeasured neck loads and
      high-frequency noise issues need to be resolved before additional BioRID II
      testing is done. A third concern with the BioRID II is the initial position of
      its head in the automotive seating posture. It is higher and more forward than
      that of the 50(th) percentile adult male.

PMID- 17458750
TI  - WorldSID Prototype Dummy Biomechanical Responses.
AB  - The results of biomechanical testing of the WorldSID prototype dummy are
      presented in this paper. The WorldSID dummy is a new, advanced Worldwide Side
      Impact Dummy that has the anthropometry of a mid-sized adult male. The first
      prototype of this dummy has been evaluated by the WorldSID Task Group against
      previously established corridors for its critical body regions. The response
      corridors are defined in the International Organization of Standardization (ISO)
      Technical Report 9790. The prototype is the first version of the WorldSID dummy
      to be built and tested. This dummy has been subjected to a rigorous program of
      testing to evaluate, first and foremost its biofidelity, but also its
      repeatability. Following this initial evaluation, any required modifications will
      be incorporated into a pre-production version of the WorldSID dummy so that it
      rates "good" to "excellent" on the ISO dummy biofidelity scale - a rating
      exceeding that of all current side impact dummies. Also, the overall WorldSID
      repeatability must not exceed a coefficient of variation of 7% at injury
      assessment level and this has to be verified for the different body regions. The
      dummy's head, neck, thorax, abdomen and pelvis were evaluated against the ISO
      technical report requirements. Testing included drop tests, pendulum impacts, and
      sled tests. The biofidelity rating of the WorldSID prototype was calculated using
      the weighted biomechanical test response procedure developed by ISO. The paper
      presents the results of the testing, which give a very positive indication of the
      dummy's potential. Based on this evaluation of the dummy biofidelity, the
      WorldSID prototype dummy exhibits a biofidelity rating of 6.15 that corresponds
      to an ISO biofidelity classification of "fair". In addition, the dummy shows good
      repeatability with a global coefficient of variation of 3.30% for the pendulum
      and rigid sled tests.

PMID- 17458751
TI  - The Hybrid III 10-Year-Old Dummy.
AB  - This paper describes the design and development of the Hybrid III 10-year-old
      crash test dummy. The size of the dummy was chosen to fill the gap between the
      Hybrid III 6-year-old and the Hybrid III small adult female dummy which is also
      about the size of a 13-year-old teenager. Characteristic dimensions and segment
      weights of the dummy are based on the anthropometry of the average 10-year-old.
      Biofidelity response guidelines for forehead, sternum and knee impacts and for
      fore/aft neck bending are scaled from the midsize adult male biofidelity
      guidelines taking into account the effects of differences in size, mass and
      material properties due to the age difference. The dummy is similar in
      construction to the other Hybrid III dummies except it has an adjustable lumbar
      spine which allows the dummy to slouch and its neck structure is aligned with its
      thoracic spine. Data are given showing the responses of the prototype dummy
      relative to its biofidelity guidelines. The prototype dummy was evaluated in out
      of-position air bag tests and three-point belt tests to evaluate its durability
      and ease of use. The prototype dummy has demonstrated acceptable biofidelity,
      repeatability and durability and the design has been approved by the SAE Hybrid
      III Dummy Family Task Group for production.

PMID- 17458752
TI  - Tensile mechanics of the developing cervical spine.
AB  - This study examined the effect of spinal development (developmental age) on the
      tensile mechanics of the cervical spine. A total of 68 isolated functional spinal
      units were subjected to tensile loading to document their mechanical response
      (tensile stiffness and ultimate failure load). Cadaveric baboon specimens,
      ranging in age from 2 to 26 human-equivalent years, were used due to the limited
      availability of human tissues in the pediatric age range. Statistically
      significant correlation was found between developmental age and both tensile
      stiffness and ultimate failure load. Furthermore, differences in these properties
      were observed as a function of spinal level. In addition to providing age-related
      data for the developing spine, our findings suggest that reasonable scaling
      relationships exist between the adult and the child spine. These relationships
      provide a basis for scaling adult properties to the child, which may abet the
      development of pediatric neck injury tolerance values.

PMID- 17458753
TI  - Investigation of Head Injury Mechanisms Using Neutral Density Technology and High
      Speed Biplanar X-ray.
AB  - The principal focus of this study was the measurement of relative brain motion
      with respect to the skull using a high-speed, biplanar x-ray system and neutral
      density targets (NDTs). A suspension fixture was used for testing of inverted,
      perfused, human cadaver heads. Each specimen was subjected to multiple tests,
      either struck at rest using a 152-mm-diameter padded impactor face, or stopped
      against an angled surface from steady-state motion. The impacts were to the
      frontal and occipital regions. An array of multiple NDTs was implanted in a
      double-column scheme of 5 and 6 targets, with 10 mm between targets in each
      column and 80 mm between columns. These columns were implanted in the
      temporoparietal and occipitoparietal regions. The impacts produced peak resultant
      accelerations of 10 to 150 g, and peak angular accelerations between 1000 and
      8000 rad/s(2). For all but one test, the peak angular speeds ranged from 17 to 22
      rad/s. The relative 3D displacements between the skull and the NDTs were
      analyzed. The localized motions of the brain generally followed loop or figure
      eight patterns, with peak displacements on the order of +/- 5 mm. These results
      can be used to further finite-element modeling efforts.

PMID- 17458754
TI  - Recent advances in brain injury research: a new human head model development and
      validation.
AB  - Many finite element models have been developed by several research groups in
      order to achieve a better understanding of brain injury. Due to the lack of
      experimental data, validation of these models has generally been limited.
      Consequently, applying these models to investigate brain responses has also been
      limited. Over the last several years, several versions of the Wayne State
      University brain injury model (WSUBIM) were developed. However, none of these
      models is capable of simulating indirect impacts with an angular acceleration
      higher than 8,000 rad/s(2). Additionally, the density and quality of the mesh in
      the regions of interest are not detailed and sensitive enough to accurately
      predict the stress/strain level associated with a wide range of impact
      severities. In this study, WSUBIM version 2001, capable of simulating direct and
      indirect impacts with a combined translational and rotational acceleration of the
      head up to 200 g and 12,000 rad/s(2) has been developed. This new finely meshed
      model, consisting of more than 314,500 elements and 281,800 nodes, also simulates
      an anatomically detailed facial bone model. An additional new feature of the
      model is the damageable material property representation of the facial bone and
      the skull, allowing it to simulate bony fractures. The model was subjected to
      extensive validation using published cadaveric test data. These data include the
      intracranial and ventricular pressure data reported by Nahum et al. (1977) and
      Trosseille et al. (1992), the relative displacement data between the brain and
      the skull reported by King et al. (1999) and Hardy et al. (2001), and the facial
      impact data reported by Nyquist et al. (1986) and Allsop et al. (1988). With the
      enhanced accuracy of model predictions offered by this new model, along with new
      experimental data, it is hoped that it will become a powerful tool to further our
      understanding of the mechanisms of injury and the tolerance of the brain to blunt
      impact.

PMID- 17458755
TI  - The effects of skull thickness variations on human head dynamic impact responses.
AB  - Variations in human skull thickness affecting human head dynamic impact responses
      were studied by finite element modeling techniques, experimental measurements,
      and histology examinations. The aims of the study were to better understand the
      influences of skull thickness variations on human head dynamic impact responses
      and the injury mechanisms of human head during direct impact. The thicknesses of
      the frontal bone of seven human cadaver skulls were measured using ultrasonic
      technology. These measurements were compared with previous experimental data.
      Histology of the skull was recorded and examined. The measured data were analyzed
      and then served as a reference to vary the skull thickness of a previously
      published three-dimensional finite element human head model to create four models
      with different skull thickness. The skull thicknesses modeled are 4.6 mm, 5.98
      mm, 7.68 mm, and 9.61 mm. These models were impacted by a cylinder with a mass of
      5.23 kg and an initial velocity of 6.33 m/s. Model responses were compared
      between models in terms of intracranial pressures, head impact accelerations,
      brain shear stresses, and skull von Mises stresses. It has been shown that the
      thickness of the skull influenced the dynamic responses of the head during direct
      impact. As skull thickness increased, skull deformation decreased as the skull
      absorbed less impact energy. However, this relationship cannot be linearly
      interpolated to the other parameters such as head acceleration and intracranial
      pressure responses. Based on model responses to half-sine wave pulses, skull and
      brain iso-stress curves were constructed for the thicker and thinner skulls.
      Thresholds for skull fracture and reversible concussion were established for the
      population represented by these skulls.

PMID- 17458756
TI  - Development and field performance of indy race car head impact padding.
AB  - The close-fitting cockpit of the modern Indy car single seat race car has the
      potential to provide a high level of head and neck impact protection in rear and
      side impacts. Crash investigation has shown that a wide variety of materials have
      been used as the padding for these cockpits and, as a result, produced varying
      outcomes in crashes. Additionally, these pads have not always been positioned for
      optimal performance. The purpose of this study was to investigate the head impact
      performance of a variety of energy-absorbing padding materials under impact
      conditions typical of Indy car rear impacts and to identify superior materials
      and methods of improving their performance as race car head pads. An extensive
      series of tests with the helmeted Hybrid III test dummy head and neck on an
      impact mini-sled was conducted to explore head padding concepts. Following this,
      a performance specification for a simplified impact test using a rigid headform
      that simulates the helmeted head was developed and recommendations for
      performance levels of head padding based on biomechanical data on helmeted head
      impacts were made. In 1997, during the time that the head pad research was being
      performed, the Indy Racing League introduced a new chassis specification for
      their cars. There were a number of rear- and side-impact crashes during that
      season that resulted in seven severe head injuries. Examples of the head padding
      in those cars were included in the experimental study. The results of the head
      pad research were used to specify new padding materials that met the new
      biomechanical criteria. The placement of the head pads was also changed for
      better location of the padding. These changes instituted in 1998 have reduced the
      number of head injuries in crashes similar to or more severe than those of 1997
      and have resulted in only occasional moderate head injuries (concussions) in the
      1998 and 1999 seasons.

PMID- 17458757
TI  - Mechanisms and factors involved in hip injuries during frontal crashes.
AB  - This study was conducted to collect data and gain insights relative to the
      mechanisms and factors involved in hip injuries during frontal crashes and to
      study the tolerance of hip injuries from this type of loading. Unembalmed human
      cadavers were seated on a standard automotive seat (reinforced) and subjected to
      knee impact test to each lower extremity. Varying combinations of flexion and
      adduction/abduction were used for initial alignment conditions and pre
      positioning. Accelerometers were fixed to the iliac wings and twelfth thoracic
      vertebral spinous process. A 23.4-kg padded pendulum impacted the knee at
      velocities ranging from 4.3 to 7.6 m/s. The impacting direction was along the
      anteroposterior axis, i.e., the global X-axis, in the body-fixed coordinate
      system. A load cell on the front of the pendulum recorded the impact force. Peak
      impact forces ranged from 2,450 to 10,950 N. The rate of loading ranged from 123
      to 7,664 N/msec. The impulse values ranged from 12.4 to 31.9 Nsec. Injuries were
      not apparent in three tests. Eight tests resulted in trauma. Fractures involving
      the pelvis including the acetabulum and proximal femur occurred in five out of
      the eight tests, and distal femoral bone fracture occurred in one test. These
      results underscore the importance of leg pre-positioning and the orientation of
      the impacting axis to produce specific types of trauma to the pelvic region of
      the lower extremity.

PMID- 17458758
TI  - Effects of Anterior-Posterior Constraint on Injury Patterns in the Human Knee
      During Tibial-Femoral Joint Loading from Axial Forces through the Tibia.
AB  - According to the National Accident Sampling System (NASS), 10% of all automobile
      accident injuries involve the knee. These injuries involve bone fracture and/or
      "soft tissue" injury. Previous investigators have determined the tibial-femoral
      (TF) joint failure load for an experimentally constrained human knee at 90
      degrees flexion. In these experiments bone fractures have been documented. During
      TF joint compression, however, anterior motion of the tibia has been noted by
      others. It was therefore the objectives of this study to document effects of
      flexion angle and anterior-posterior joint constraint on the nature and severity
      of knee injury during TF compression loading via axial loads in the tibia. The
      effect of flexion angle was examined using 10 unconstrained human knees from 5
      cadavers aged 73.2+/-9.4 years. The tibial-femoral joint was loaded in
      compression as a result of axial loading along the tibia using a servo-hydraulic
      testing machine until gross failure with the knee flexed 60 degrees or 120
      degrees . Pressure sensitive film measured the distribution of internal TF joint
      loads. Both 60 degrees and 120 degrees flexed preparations failed by rupture of
      the anterior cruciate ligament (ACL) at 4.6+/-1.2 kN, and the internal joint
      loads were significantly higher (2.6+/-1.5 kN) on the medial versus the lateral
      (0.4+/-0.5 kN) aspect of the tibial plateau. The effect of anterior-posterior
      (AP) constraint of the femur along the longitudinal axis of the femur was
      investigated in a second series of tests using the same TF joint loading protocol
      on 6 pairs of human joints (74.3+/-10.5 years) flexed at 90 degrees . The primary
      mode of failure for the AP constrained joints was fracture of bone via the
      femoral condyle at a maximum load of 9.2+/-2.6 kN. The mode of failure for
      unconstrained joints was primarily due to rupture of the ACL at a maximum load of
      5.8+/-2.9 kN. Again, the pressure film indicated an unequal internal TF load
      distribution for the unconstrained knee (medial plateau 4.1+/-1.9 kN versus
      lateral plateau 0.8+/-0.8 kN). However, there was a more equal distribution of
      internal loads between the medial (4.4+/-1.8 kN) and lateral (2.8+/-1.9 kN)
      aspects of the tibial plateau in the constrained joints. This study showed that
      the mechanism of tibial-femoral knee joint injury and internal TF joint load
      distribution depends on the degree of AP constraint offered by the test
      apparatus. Flexion angle did not significantly affect failure load or the
      mechanism of failure for the unconstrained knee. The findings from this study may
      be useful in understanding the complex failure mechanisms for an unconstrained
      knee under axial compression loads in the tibia during automobile crashes.

PMID- 17458759
TI  - Lower Limb: Advanced FE Model and New Experimental Data.
AB  - The Lower Limb Model for Safety (LLMS) is a finite element model of the lower
      limb developed mainly for safety applications. It is based on a detailed
      description of the lower limb anatomy derived from CT and MRI scans collected on
      a subject close to a 50th percentile male. The main anatomical structures from
      ankle to hip (excluding the hip) were all modeled with deformable elements. The
      modeling of the foot and ankle region was based on a previous model Beillas et
      al. (1999) that has been modified. The global validation of the LLMS focused on
      the response of the isolated lower leg to axial loading, the response of the
      isolated knee to frontal and lateral impact, and the interaction of the whole
      model with a Hybrid III model in a sled environment, for a total of nine
      different set-ups. In order to better characterize the axial behavior of the
      lower leg, experiments conducted on cadaveric tibia and foot were reanalyzed and
      experimental corridors were proposed. Future work will include additional
      validation of the model using global data, joint kinematics data, and deformation
      data at the local level.

PMID- 17458760
TI  - Biofidelity of TRL Legform Impactor and Injury Tolerance of the Human Leg in
      Lateral Impact.
AB  - In nonfatal car-pedestrian accidents, lower extremities are the most commonly
      injured body parts. The test device used to evaluate the car-front aggressiveness
      regarding the risk of these injuries is a legform impactor. Injury-related
      factors causing AIS 2+ injury in the human lower leg when exposed to a lateral
      impact representing a pedestrian accident should be identified. One of the test
      devices commonly used to evaluate the risk is the legform impactor developed by
      the Transport Research Laboratory (TRL). However, information about the
      biofidelity of this impactor and leg injury tolerance curves is lacking. Thus,
      the objectives of this research are: 1) to determine possible injury-related
      factor(s) causing AIS 2+ injury in the human lower leg when exposed to a lateral
      impact simulating a pedestrian accident; 2) to evaluate the biofidelity of the
      current version of the TRL legform impactor; and 3) to propose injury reference
      value for estimation of the leg and knee joint injury risk by means of a legform
      impactor. To determine factors causing leg fracture and knee joint ligament
      injury, injury-related factors were statistically tested in the present study. In
      this estimation, we analyzed knee lateral force, knee bending moment, knee shear
      displacement (i.e., relative displacement between the leg and thigh at the knee
      joint level in a lateral direction), knee bending angle, leg acceleration, and
      the impact force as factors that could correlate with the occurrence of the leg
      injuries. Regarding tibia fracture, both the impact force and leg acceleration
      were found to be significant factors. For ligament injury, it was found that only
      the shearing displacement was indeed very likely to be a significant factor. The
      TRL legform impactor was evaluated by comparing its responses with the published
      experimental results obtained using postmortem human subjects (PMHSs). The
      evaluation was done under two conditions: impact point 84 mm below the knee joint
      center (shearing tests) and impact point near the ankle area (bending tests). Two
      impact speeds were used: 5.56 m/s and 11.11 m/s. Impact force, shear
      displacement, and bending angle were applied to measure the TRL legform impactor
      biofidelity. In general, the impactor responses were outside the biofidelity
      corridors determined using PMHSs. The exception was the impact force in the
      bending setup at a speed of 5.56 m/s. To estimate the leg injury risk when using
      the TRL legform impactor, we determined transfer coefficients between the
      responses of this impactor and the human leg. Using these coefficients, we
      suggest an impact force of 6.9 kN and a shearing displacement of 7.9 mm as
      criteria for 50-percentile risk of the leg fracture and ligament injury with the
      TRL legform impactor.

PMID- 17458761
TI  - Prediction of airbag-induced forearm fractures and airbag aggressivity.
AB  - This study continued the biomechanical investigations of forearm fractures caused
      by direct loading of steering-wheel airbags during the early stages of
      deployment. Twenty-four static deployments of driver airbags were conducted into
      the forearms of unembalmed whole cadavers using a range of airbags, including
      airbags that are depowered as allowed by the new federal requirements for frontal
      impact testing. In general, the depowered airbags showed a reduction in incidence
      and severity of forearm fractures compared to the pre-depowered airbags tested.
      Data from these twenty-four tests were combined with results from previous
      studies to develop a refined empirical model for fracture occurrence based on
      Average Distal Forearm Speed (ADFS), and a revised value for fifty-percent
      probability of forearm-bone fracture of 10.5 m/s. Bone mineral content, which is
      directly related to forearm tolerance, was found to be linearly related to arm
      mass. The ADFS criterion was found to be effective in predicting forearm
      fracture, regardless of the airbag system, subject size, and age. Additional
      testing was conducted to examine the principles underlying the ADFS criterion.
      Specifically, static airbag-deployments were conducted into cylinders of
      different mass to study the relationships between forearm mass and forearm-to
      airbag module distance relative to ADFS. ADFS was found to be linearly but
      inversely related to cylinder mass, and to the distance between the forearm and
      airbag module. The suitability of using existing surrogate arms to assess airbag
      aggressivity relative to forearm fractures using ADFS was explored as well.

PMID- 17458762
TI  - 3D simulation of needle-tissue interaction with application to prostate
      brachytherapy.
AB  - This paper presents a needle-tissue interaction model that is a 3D extension of
      prior work based on needle and tissue models discretized using the Finite Element
      Method. The use of flexible needles necessitates remeshing the tissue during
      insertion, since simple mesh-node snapping to the tip can be detrimental to the
      simulation. In this paper, node repositioning and node addition are the two
      methods of mesh modification examined for coarse meshes. Our focus is on
      numerical approaches for fast implementation of these techniques. Although the
      two approaches compared, namely the Woodbury formula (matrix inversion lemma) and
      the boundary condition switches, have the same computational complexity, the
      Woodbury formula is shown to perform faster due to its cache-efficient order of
      operations. Furthermore, node addition is applied in constant time for both
      approaches, whereas node repositioning requires longer and variable computational
      times. A method for rendering the needle forces during simulated insertions into
      a 3D prostate model has been implemented. Combined with a detailed anatomical
      segmentation, this will be useful in teaching the practice of prostate
      brachytherapy. Issues related to discretization of such coupled (e.g., needle
      tissue) models are also discussed.

PMID- 17458763
TI  - Photorealistic modeling of tissue reflectance properties.
AB  - OBJECTIVE: For Minimally Invasive Surgery (MIS) procedures, specular highlights
      constitute important visual cues for gauging tissue deformation as well as
      perceiving depth and orientation. This paper describes a novel reflectance
      modeling technique that is particularly suitable for simulating light interaction
      behavior with mucus-covered tissue surfaces. METHODS: The complex and largely
      random tissue-light interaction behavior is modeled with a noise-based approach.
      In the proposed technique, Perlin noise is used to modulate the shape of specular
      highlights and imitate the effects of the complex tissue structure on reflected
      lighting. For efficient execution, the noise texture is generated in pre
      processing and stored in an image-based representation, i.e., a reflectance map.
      At run-time, the graphics hardware is used to attain per-pixel control and
      achieve realistic tissue appearance. RESULTS: The reflectance modeling technique
      has been used to replicate light-tissue reflection in surgical simulation. By
      comparing the results acquired against those obtained from conventional per
      vertex Phong lighting and OpenGL multi-texturing, it is observed that the noise
      based approach achieves improved tissue appearance similar to that observed in
      real procedures. Detailed user evaluation demonstrates the quality and practical
      value of the technique for increased perception of photorealism. CONCLUSION: The
      proposed technique presents a practical strategy for surface reflectance modeling
      that is suitable for real-time interactive surgical simulation. The use of
      graphics hardware further enhances the practical value of the technique.

PMID- 17458764
TI  - New approaches to catheter navigation for interventional radiology simulation.
AB  - For over 20 years, interventional methods have improved the outcomes of patients
      with cardiovascular disease. However, these procedures require an intricate
      combination of visual and tactile feedback and extensive training. In this paper,
      we describe a series of novel approaches that have led to the development of a
      high-fidelity simulation system for interventional neuroradiology. In particular,
      we focus on a new approach for real-time deformation of devices such as catheters
      and guidewires during navigation inside complex vascular networks. This approach
      combines a real-time incremental Finite Element Model (FEM), an optimization
      strategy based on substructure decomposition, and a new method for handling
      collision response in situations where the number of contact points is very
      large. We also briefly describe other aspects of the simulation system, from
      patient-specific segmentation to the simulation of contrast agent propagation and
      fast volume-rendering techniques for generating synthetic X-ray images in real
      time. Although currently targeted at stroke therapy, our results are applicable
      to the simulation of any interventional radiology procedure.

PMID- 17458765
TI  - Implant position calculation for acetabular cup placement considering pelvic
      lateral tilt and inclination.
AB  - OBJECTIVE: The purpose of this study was to investigate the relationship of cup
      position versus pelvic lateral tilt and inclination. While computer assisted
      navigation systems use only the pelvic frontal plane for cup placement, it is
      important to realize the effect of leg length differences or increased pelvic
      inclination, i.e., caused by contracted hip flexors. MATERIALS AND METHODS: Using
      a sawbone model of the pelvis, cup position measurements were performed with
      different pelvic inclination and lateral tilt angles. The measured values were
      compared with outcome variables from a mathematical model. A computer program was
      developed to perform a reverse calculation to verify the mathematical model.
      RESULTS: The mathematical model proved correct in the sawbone pelvis experiment.
      The cup position changed from 15 degrees anteversion in 0 degrees pelvic
      inclination to 0.5 degrees retroversion in 15 degrees pelvic inclination.
      Regardless of pelvic inclination, the vertical cup projection stayed in a safe
      range of 37-47 degrees. Leg length differences greater than 3 cm have significant
      effects on the positioning of acetabular cups in the frontal plane. CONCLUSIONS:
      Using computer navigation, it is possible to determine pelvic inclination and
      lateral tilt during an operation by calculating the angular difference between
      the anatomic frontal plane and the "real world" frontal plane (i.e., the OR
      table). This method may be helpful in increasing the accuracy of positioning of
      acetabular cups.

PMID- 17458766
TI  - Implementation of a new navigated parallel drill guide for femoral neck
      fractures.
AB  - Trauma navigation modules often use conventional mechanical surgical tools for
      basic simulation of drilling procedures or single screw placement. However, the
      precise parallel placement or specific angles that may be required are not
      displayed on the navigation screen. A more complex mechanical tool, a parallel
      drill guide (PDG) for femoral neck fractures, was integrated into a navigation
      module as part of this study, thus combining the advantages of mechanical tools
      with the benefits of fluoroscopic navigation. To implement a conventional PDG
      with a conventional navigation system, the tool was equipped with a non
      detachable reflective marker array. Navigation engineers adapted the software to
      enable the navigated PDG to be displayed. We evaluated the conventional technique
      in comparison with the navigated technique using plastic bone models and a fresh
      frozen cadaver. Implementation of the navigated PDG did not pose any problems, in
      terms of either the software or the surgical procedure itself. The total
      operation time was extended by 30%, but the radiation time for the navigated
      group was reduced by 50%. No software or hardware-related failures occurred.
      Complete integration of a cannulated parallel drill guide into a navigation
      system has been successfully implemented. Continuous display of the mechanical
      guide with two parallel trajectories on the navigation screen enables safe,
      efficient screw placement within mechanical guidelines, without the need for
      additional radiographic control once initial registration has been completed.

PMID- 17458767
TI  - The transverse pelvic plane: a new and practical reference frame for hip
      arthroplasty.
AB  - Acetabular orientation is a crucial part of the planning and performance of hip
      arthroplasty. Currently, most surgeons use the anterior pelvic plane (APP) to
      orient themselves when navigating the acetabulum, despite the fact that the
      anterior superior iliac spine (ASIS) of the unaffected side is not accessible in
      the lateral position. We have identified another plane, the transverse pelvic
      plane (TPP), relying on both posterior superior iliac spines and the ASIS of the
      affected side. In a CT-based study, this plane was found to be as reliable as the
      APP for the orientation of the cup in both anteversion and inclination. The
      substantial variation in both measurements between patients is documented, and
      their relation to the "safe zone" is shown. We recommend consideration of the TPP
      by surgeons who perform arthroplasty in the lateral position. It may reduce
      operating time and improve accuracy in computer-assisted arthroplasty.

PMID- 17458769
TI  - Influenza: evolving strategies in treatment and prevention.
AB  - Influenza A and B are important causes of respiratory illness in all age groups.
      Influenza causes seasonal outbreaks globally, and (rarely) pandemics. In the
      United States, seasonal influenza epidemics account for > 200,000
      hospitalizations and > 30,000 deaths annually. More than 90% of deaths are in the
      elderly. The toll is considerably higher during pandemics. Clinical features of
      influenza infection overlap with other respiratory pathogens (particularly
      viruses). The diagnosis is often delayed due to low suspicion and the limited use
      of specific diagnostic tests. Rapid diagnostic tests are widely available and
      allow detection of influenza antigen in respiratory secretions within 1 hour;
      however, sensitivity ranges from 40 to 80%. Currently, four drugs are available
      to treat or prevent influenza. These include the adamantanes (i.e., amantadine
      and rimantadine) and the neuraminidase inhibitors (i.e., oseltamivir and
      zanamivir). Adamantanes are active against influenza A but not influenza B.
      However, recent emergence of adamantane resistance has rendered these agents
      ineffective. Hence, adamantanes are not currently recommended in the United
      States. The neuraminidase inhibitors (NAIs) are effective in treating influenza A
      or B, and for prophylaxis in selected adults and children. Resistance to NAIs is
      rare, but influenza strains resistant to oseltamivir have been detected. Vaccines
      are the cornerstone of influenza control. Currently, trivalent inactivated
      vaccine (TIV) and live attenuated influenza vaccine (LAIV) are available. These
      agents reduce mortality and morbidity in high-risk patients (i.e., the elderly or
      patients with comorbidities), and expanding the use of vaccines to healthy
      children and adults reduces the incidence of influenza, pneumonia, and
      hospitalizations due to respiratory illnesses in the community.

PMID- 17458770
TI  - Pandemic (avian) influenza.
AB  - Pandemics of influenza have been reported since the early sixteenth century.
      Recent pandemics include the Spanish flu (H1N1) from 1918 to 1920 (resulting in
      approximately 50 million deaths worldwide); the Asian flu (H2N2) from 1957 to
      1958 (resulting in more than 1 million deaths); the Hong Kong flu (H3N2) from
      1968 to 1970 (responsible for approximately 700,000 deaths). Avian influenza
      viruses have now been identified as a source of novel hemagglutinin (HA) and
      neuraminidases (NAs) associated with pandemics. Although infections in humans
      with avian strains are uncommon, several outbreaks of severe influenza with
      highly virulent H5N1 strains derived from infected poultry were reported in China
      and other Asian countries since 2003. Large-scale culling operations and
      intensified surveillance led to eradication of H5N1 infection in poultry in some
      countries, but H5N1 infection in wild birds and domestic poultry has become
      endemic in many countries. The potential exists for global pandemics of
      unprecedented magnitude. In this review, we discuss the epidemiology and genetics
      of avian influenza viruses, the potential for transmission of disease to humans,
      clinical features of avian influenza infections in humans, appropriate diagnostic
      testing, and treatment. We also discuss global efforts for disease prevention via
      a host of programs, including intensified surveillance, culling of infected
      birds, education of medical personnel and the public, production of vaccines, and
      use of specific antiviral agents (e.g., adamantanes and neuraminidase
      inhibitors).

PMID- 17458771
TI  - Respiratory syncytial virus infection in adults.
AB  - Respiratory syncytial virus (RSV) is a common winter time respiratory virus that
      affects persons of all ages and is the major cause of serious lower respiratory
      tract infections in young children. However, RSV is also an important pathogen in
      adults, particularly in the elderly, patients with chronic lung disease, or those
      with impaired immunity. Clinical features of RSV infections overlap with other
      respiratory viruses, so laboratory tests are required to establish the diagnosis.
      Reverse transcriptase polymerase chain reaction (RT-PCR) of samples from nasal
      swabs, sputum, or bronchoalveolar lavage is a sensitive test to substantiate the
      diagnosis. Serologies are useful in epidemiological surveys. The clinical course
      of RSV infections is variable. In infants, RSV presents as bronchiolitis. In
      adults, mild to moderate upper respiratory tract illness is characteristic.
      However, severe pneumonia can occur, particularly in the elderly with
      comorbidities or compromised immune status. Humoral antibodies confer partial
      immunity to RSV infection and disease severity; cellular immunity is important to
      eradicate RSV in established infections. Treatment of RSV infections is often
      supportive. Aerosolized ribavirin is approved for RSV infections in infants; its
      role in adults is controversial. Infection control measures are critical to limit
      spread of RSV. Currently, RSV vaccines are not available, but candidate vaccines
      are being developed.

PMID- 17458772
TI  - Rhinovirus and coronavirus infections.
AB  - Rhinoviruses and coronaviruses cause the majority of common colds and play a part
      in more serious respiratory illnesses that lead to increased morbidity and
      mortality. Patients who are infants or elderly, have asthma or chronic
      obstructive pulmonary disease (COPD), or are immunosuppressed have increased
      frequency of rhinovirus-related respiratory complications. Newer diagnostic tests
      such as reverse transcriptase polymerase chain reaction (RT-PCR) have greatly
      expanded our understanding of the importance of these respiratory viruses.
      Although there are no currently approved antiviral agents for clinical use, our
      increased understanding of the virus-host interaction should lead to new
      intervention strategies.

PMID- 17458773
TI  - Hantavirus cardiopulmonary syndrome.
AB  - Hantavirus cardiopulmonary syndrome (HCPS) is caused by infection with multiple
      types of hantaviruses throughout the Americas. All strains induce a pulmonary
      capillary leak syndrome with cardiogenic shock in severe cases, and almost all
      strains have an overall mortality rate of 35%. Some strains in South America are
      commonly associated with either mild disease without pulmonary edema or severe
      disease with pulmonary hemorrhage. Early recognition during the thrombocytopenic
      prodrome phase and transport to intensive care improve survival, due to very
      rapid progression of respiratory failure and shock in some patients. Limited
      fluid replacement, early inotropic therapy, and mechanical ventilation also
      improve survival. Extracorporeal membrane oxygenation (ECMO) has been life saving
      for patients with refractory shock. Ribavirin does not appear to reduce
      mortality, but hyperimmune serum offers a promising future therapy because
      survival is correlated with higher neutralizing antibody titers at admission.

PMID- 17458774
TI  - Severe acute respiratory syndrome (SARS) coronavirus.
AB  - The global severe acute respiratory syndrome (SARS) outbreak was the first
      pandemic of the 21st century. Although the outbreak was successfully controlled,
      evidence that SARS emerged from an animal reservoir has raised concerns that
      another pandemic could occur. This review discusses the likelihood of another
      SARS pandemic and reviews the epidemiological and clinical features of the
      disease with an emphasis on the clinical presentation, diagnosis, and management
      of SARS.

PMID- 17458775
TI  - Human metapneumovirus.
AB  - Human metapneumovirus (hMPV) is a newly discovered paramyxovirus associated with
      upper and lower respiratory tract infections most commonly in young children,
      elderly subjects, and immunocompromised patients. hMPV can cause severe
      infections such as bronchiolitis and pneumonia and is responsible for 5 to 10% of
      hospitalizations of children suffering from acute respiratory tract infections.
      Such infections are indistinguishable from those caused by human respiratory
      syncytial virus. The first hMPV infection occurs during early childhood but
      reinfections are common throughout life, especially in older subjects. Molecular
      methods such as reverse transcriptase polymerase chain reaction (RT-PCR) are the
      preferred diagnostic modality due to fastidious growth in cell culture. Promising
      experimental models have been developed to better understand hMPV pathogenesis
      and to evaluate the potential effect of different therapeutic modalities. No
      commercial treatments are yet available for hMPV, although ribavirin has shown
      activity both in vitro and in animal models. Live attenuated vaccines produced by
      reverse genetics have also shown good efficacy in animals.

PMID- 17458776
TI  - Community respiratory virus infections in immunocompromised patients:
      hematopoietic stem cell and solid organ transplant recipients, and individuals
      with human immunodeficiency virus infection.
AB  - Infection is the leading cause of morbidity and mortality in immunocompromised
      patients such as hematopoietic/solid organ transplant recipients and individuals
      with human immunodeficiency virus. Community respiratory virus infections are
      increasingly recognized as a significant threat to these patients. This article
      reviews current information in the clinical field of community respiratory
      viruses, including several newly discovered respiratory viruses. Respiratory
      syncytial virus, influenza viruses, parainfluenza viruses, and adenoviruses cause
      the most serious disease in immunocompromised hosts, but other respiratory
      viruses are becoming increasingly appreciated as a cause of both upper and lower
      respiratory tract disease. The clinical impact of these new viruses, including
      human metapneumovirus, non-SARS human coronaviruses, and human bocavirus, is not
      yet clear. Modern molecular technology has made the discovery of new viruses
      possible; the use of these new technologies in direct patient care is not yet
      standard but is becoming increasingly utilized. Clinicians should appreciate the
      potential for the development of antiviral resistance to influenza antivirals in
      immunocompromised patients.

PMID- 17458777
TI  - Progress in respiratory virus vaccine development.
AB  - Viral respiratory infections continue to cause significant morbidity and
      mortality in infants and young children as well as in at-risk adults and the
      elderly. Although many viral pathogens are capable of causing acute respiratory
      disease, vaccine development has to focus on a limited number of pathogens (i.e.,
      agents that commonly cause serious lower respiratory disease). Inactivated and,
      more recently, live attenuated influenza virus vaccines are the mainstay of
      interpandemic influenza prevention, but vaccines are not available yet for other
      important viruses such as respiratory syncytial virus, metapneumovirus, the
      parainfluenza viruses, and avian influenza viruses with pandemic potential.
      Reverse genetics systems that allow rational vaccine development are now widely
      used, and considerable progress has been made in preclinical and clinical
      development of novel respiratory virus vaccines.

PMID- 17458778
TI  - New sesquiterpene lactone and neolignan glycosides with antioxidant and anti
      inflammatory activities from the fruits of Illicium oligandrum.
AB  - Phytochemical investigations of the fruits of Illicium oligandrum resulted in a
      new sesquiterpene lactone, 3 beta-benzoyloxy-10-deoxyfloridanolide (1), and three
      new neolignan glycosides, including two dihydrobenzofuran neolignan glycosides,
      (7 R,8 S)-9-O-beta-D-xylopyranosyl-9'-O-alpha- L-rhamnopyranosyl-(1-->6)-beta-D
      glucopyranosyldihydrodehydrodiconiferyl alcohol (2) and (7 R,8 S)-9-O-shikimoyl-4
      O-beta-D-glucopyranosyldihydrodehydrodiconiferyl alcohol (3) and one 8- O-4'
      neolignan glycoside, (7 S,8 R)-1-[4-O-(beta-D-glucopyranosyl)-3-methoxyphenyl]-2
      [4-(3-hydroxypropyl)-2,6-dimethoxyphenoxy]-1,3-propanediol (4), together with
      three known sesquiterpene lactones (5 - 7) and two known neolignan glycosides (8
      and 9). Their structures were elucidated on the basis of 1D, 2D NMR, HR-MS and
      chemical evidence. Compounds 3 and 4 showed moderate antioxidant activity with
      the inhibitory rates 13.30% and 9.30% at 1.0 x 10(-5) M, respectively. Compounds
      3 and 9 exhibited anti-inflammatory activity with the inhibitory rates 67.0% and
      51.0% at 1.0 x 10(-5) M, respectively.

PMID- 17458779
TI  - Effect of cantharidin, cephalotaxine and homoharringtonine on "in vitro" models
      of hepatitis B virus (HBV) and bovine viral diarrhoea virus (BVDV) replication.
AB  - The effect as antiviral agents versus viral hepatitis B and C of three compounds
      purified from natural products commonly used as remedies in traditional Chinese
      medicine, cantharidin, cephalotaxine and homoharingtonine, was investigated. To
      assess the activity of these compounds against flavivirus, we used bovine viral
      diarrhoea virus (BVDV) as a surrogate for hepatitis C virus (HCV). Anti-BVDV
      activity was determined by reduction in BVDV-RNA production and protection of
      infected embryonic bovine trachea (EBTr) cells against the cytopathic effect of
      BVDV. The effect versus hepatitis B virus (HBV) was investigated by measuring
      HBsAg and HBV-DNA release from hepatoblastoma HepG2 2.2.15 cells infected with
      HBV. As positive control we used the standard anti-HBV and anti-HCV drugs,
      lamivudine and ribavirin, respectively. Up to 100 microM lamivudine and ribavirin
      did not induce cell toxicity, whereas they induced dose-dependent anti-HBV and
      anti-BVDV effects, respectively. In the same range, cantharidin, cephalotaxine
      and homoharringtonine induced toxicity in EBTr cells and had no protective effect
      against BVDV. In contrast, they were able to inhibit HBV production at
      concentrations 10- to 100-fold lower than those inducing cell toxicity, which
      suggests that they are useless for the treatment of infection by flaviviruses,
      but potentially useful in combined therapy against hepatitis B.

PMID- 17458780
TI  - [Proceedings of the 99th Annual Meeting of the Swiss Society of Ophthalmology
      SOG/SSO, Lugano, September 6 - 9 2006].

PMID- 17458781
TI  - A surgical approach to treat chronic epiphora and/or muculopurulent discharge in
      patients with permeable lacrimal drainage system.
AB  - BACKGROUND: This study reports the one-year success rate of a new surgical
      approach to treat symptoms of chronic epiphora and/or mucopurulent discharge
      refractive to at least six months of medical treatment in patients with permeable
      lacrimal drainage system (irrigation test). PATIENTS AND METHODS:  DESIGN:
      retrospective chart review analysis. PARTICIPANTS: seventeen consecutive patients
      referred from a private praxis to an eye clinic to treat, by surgery, symptoms of
      either chronic epiphora (8/17), mucopurulent discharge (7/17), or both (2/17).
      INTERVENTION: Piffaretti's non-laser transpunctal endoscopic diagnostic/surgical
      lacrimal drainage procedure (17/17), lacrimal punctoplasty (16/17),
      conjunctivochalasisplasty (5/17), lateral canthoplasty (1/17), and/or both
      conjunctivochalasisplasty and lateral canthoplasty (3/17). In the majority of
      these patients (13/17) partial obstructions within the lacrimal canaliculus
      (3/17), the ductus nasolacrimalis (7/17), or both (3/17) were observed
      endoscopically and removed with Piffaretti's lacrimal trephines. MAIN OUTCOME
      MEASURES: patient's self-assessment of symptom improvement one year after
      surgery. RESULTS: One year after surgery, 88 % (15/18) of patients had a marked
      improvement of their symptoms, 64 % (11/17) of them even reporting as being
      symptom free. When conducted (14/17), irrigation always revealed a permeable
      lacrimal system (test not performed in a lost-to-follow-up and in two symptom
      free patients). CONCLUSIONS: Surgery can be an alternative therapeutic option for
      patients who have a permeable lacrimal drainage system and suffer from chronic
      epiphora and/or mucopurulent discharge that do not respond to conventional
      conservative medical therapies.

PMID- 17458782
TI  - Superficial conjunctiva cauterization to reduce moderate conjunctivochalasis.
AB  - AIM: We report here a simple surgical approach to reduce moderate
      conjunctivochalasis. PATIENTS AND METHODS: A non-comparative prospective
      interventional case series study of fifteen consecutive patients with moderate
      conjunctivochalasis was carried out. On the inferior bulbar conjunctiva 10 to 20
      superficial burns were performed with an electrical bipolar cauter to reduce
      moderate conjunctivochalasis. Before and around a mean time of six months after
      surgery digital photographs of the conjunctivochalasis were taken at the slit
      lamp. The maximal height of the conjunctivochalasis above the lower eyelid margin
      measured before surgery was compared with the height of the conjunctivochalasis
      measured after surgery around the same location (one eye per patient). RESULTS:
      In each patient, gentle and superficial cauterization induced contraction of the
      bulbar conjunctiva and reduction of the conjunctivochalasis. No complications
      were noted during or after the procedure. Mean (+/- SD) maximal
      conjunctivochalasis height above the lower eyelid margin was higher before (2.3
      +/- 0.9 mm) than after surgery (0.8 +/- 0.6 mm). Preoperative values of
      conjunctivochalasis height were significantly (p < 0.001) different from the
      postoperative ones (Wilcoxon rank signed test). CONCLUSIONS: Gentle superficial
      cauterization of the inferior bulbar conjunctiva can induced significant
      reduction of a moderate conjunctivochalasis.

PMID- 17458783
TI  - Antibiotic susceptibilities of bacteria isolated from ophthalmic specimens
      between 1984 and 2005 in Zurich, Switzerland.
AB  - BACKGROUND: Increasing resistance of bacteria cultured from ophthalmic specimens
      to antibiotic therapy has been documented worldwide. Inappropriate prescribing
      practices are thought to represent a major risk factor for antibiotic resistance.
      This study investigates the pattern of bacterial antibiotic susceptibility in
      Zurich, Switzerland over a period of twenty years. METHODS: Antibiotic
      susceptibilities of bacterial isolates from all ophthalmic specimens cultured at
      the Institute of Medical Microbiology in Zurich between 1984 and 2005 were
      analysed retrospectively. RESULTS: A total of 7,862 ocular surface samples have
      been collected. 3,010 specimens (38.3 %) were positive for aerobic bacteria. The
      strains isolated most frequently were Staphylococcus aureus (23.9 %), coagulase
      negative staphylococci (16.1 %), Pseudomonas aeruginosa (10.0 %), Haemophilus
      influenzae (6.3 %), Escherichia coli (5.1 %), Serratia marcescens (4.7 %), and
      Streptococcus pneumoniae (3.9 %). Various bacteria accounted for the remaining
      30.0 %. Susceptibility of these strains to the aminoglycosides, quinolones, and
      cephalosporins tested did not change over this period of time. CONCLUSION: The
      data suggest that bacteria cultured from ophthalmic specimens in Zurich,
      Switzerland have not changed their pattern of antibiotic susceptibility over the
      past 20 years.

PMID- 17458784
TI  - [Quality assurance in biometry before cataract surgery: which patients have an
      increased risk of aberrance from target refraction?].
AB  - BACKGROUND: An important factor for patient satisfaction after cataract surgery
      is the achievement of the planned target refraction. The formulae which are used
      to calculate the necessary refractive power of the intraocular lens (IOL) to be
      implanted have been improved over time in order to deliver exact predictions even
      in those cases in which the measurements of an eye deviate greatly from the norm.
      We examined which of the routinely measured biometric values have an influence on
      reaching target refraction. PATIENTS AND METHODS: This retrospective
      investigation reports on a case series of 153 eyes of 146 patients within 6
      months in which a cataract operation was performed. The average age at the time
      of operation was 73.5 years. Four measurements were taken preoperatively:
      refraction (Ref), axial length (AL), corneal refractive power (CR) and anterior
      chamber depth (ACD). Each of these measurements was examined regarding its
      influence on the refractive outcome. One of three end points was possible for
      each eye: achievement of target refraction within +/- 0.5 dpt, aberrance from
      target refraction by more than + 0.5 dpt and aberrance from target refraction by
      more than - 0.5 dpt. A multivariate regression analysis was performed in which
      aberrance from target refraction was defined as the dependent variable and the
      four mentioned measurements were set as independent variables. RESULTS: Of the
      153 eyes, in 91 eyes the target refraction was achieved within 0.5 dpt (group 1).
      In 37 eyes the aberrance from target refraction was more than - 0.5 dpt (group 2)
      and in 25 eyes it was more than + 0.5 dpt (group 3). The mean measurement values
      in groups 1, 2 and 3 were as follows: for preoperative refraction 0.0 dpt/0.5
      dpt/0.625 dpt, for corneal refractive power 42.84 dpt/42.29 dpt/42.67 dpt, for
      axial length 23.41 mm/23.36 mm/23.73 mm and for anterior chamber depth 3.07
      mm/3.00 mm/3.20 mm. No statistically significant relation between the respective
      measured values or a combination thereof and the refractive result could be
      demonstrated. CONCLUSIONS: The formulae for calculating IOL power available today
      are highly developed and integrate preoperative biometries in a non-linear way,
      so that there is little difference between measurements within the norm and
      outlying ones concerning their influence on the refractive result. When
      conducting quality assurance efforts, we recommend to direct attention to factors
      influencing anterior chamber depth.

PMID- 17458785
TI  - Phosphate concentrations in antiglaucoma medication.
AB  - BACKGROUND: Eye drops may contain phosphates as part of their buffer system. In
      the presence of epithelial keratopathy a high concentration of phosphate favours
      corneal calcification. To date European legislation does not require a
      quantitative declaration of the phosphates since buffers are regarded as
      additives. The knowledge of the phosphate concentration in medications helps to
      prevent corneal calcifications. Our study gives an overview on the amount of
      phosphate contained in antiglaucoma drops. METHODS: 21 samples of commercially
      available antiglaucoma drops were tested. The quantification of phosphate was
      performed using the molybdate method on a Modular P autoanalyzer. RESULTS: 10 of
      21 (47 %) glaucoma drops had a phosphate concentration above physiological levels
      (> 1.45 mmol/L). A concentration higher than 100 mmol/L was found in four
      preparations that contained timolol. CONCLUSIONS: Many antiglaucoma drops contain
      unphysiological levels of phosphate, very high concentrations are found in some
      beta-blockers. These preparations have the potential to favour the formation of
      insoluble crystalline calcium phosphate deposits when used on a damaged corneal
      surface, and should therefore be avoided.

PMID- 17458786
TI  - Comparison of tendency-oriented perimetry and dynamic strategy in octopus
      perimetry as a screening tool in a clinical setting: a prospective study.
AB  - OBJECTIVE: The aim of this study was to compare the results of tendency-oriented
      perimetry (TOP) and a dynamic strategy in octopus perimetry as screening methods
      in clinical practice. DESIGN: A prospective single centre observational case
      series was performed. PARTICIPANTS AND METHODS: In a newly opened general
      ophthalmologic practice 89 consecutive patients (171 eyes) with a clinical
      indication for octopus static perimetry testing (ocular hypertension or
      suspicious optic nerve cupping) were examined prospectively with TOP and a
      dynamic strategy. The visual fields were graded by 3 masked observers as normal,
      borderline or abnormal without any further clinical information. RESULTS: 83%
      eyes showed the same result for both strategies. In 14% there was a small
      difference (with one visual field being abnormal or normal, the other being
      borderline). In only 2.9% of the eyes (5 cases) was there a contradictory result.
      In 4 out of 5 cases the dynamic visual field was abnormal and TOP was normal. 4
      of these cases came back for a second examination. In all 4 the follow-up
      examination showed a normal second dynamic visual field. CONCLUSIONS: Octopus
      static perimetry using a TOP strategy is a fast, patient-friendly and very
      reliable screening tool for the general ophthalmological practice. We found no
      false-negative results in our series.

PMID- 17458787
TI  - [Positive ibopamine provocative test in normal-tension glaucoma suspects].
AB  - BACKGROUND: Ibopamine is an alpha-adrenergic agent and causes an elevation of
      intraocular pressure in eyes with increased outflow resistance. It has been
      proposed as a test substance for the detection of early ocular hydrodynamic
      disorders. PATIENTS AND METHODS: A total of 64 normal-tension glaucoma suspect
      eyes without anti-hypertensive treatment were enrolled. A daily pressure curve
      was registered with measurements at 7:00 am, 8:00 am, 12:00 am, 17:00 pm using an
      applanation tonometer and a contour tonometer followed by instillation of
      ibopamine 2% in both eyes. Tonometry was performed every 15 minutes during the
      following hour. An IOP increase of > 2.0 mmHg was considered positive. RESULTS:
      The positive test group showed a significant pressure increase from 18.04 to
      22.06 mmHg. Ocular pulse amplitude increased from 2.96 to 3.97 mmHg and was
      positively correlated with the pressure. Intraocular pressure was unchanged in
      the negative test group. Central corneal thickness was not significantly
      different in the two groups (p = 0.32). CONCLUSIONS: Ibopamine 2% eye drops have
      a positive pressure effect in 50% of suspected normal-tension glaucoma eyes and
      may differentiate between eyes with normal trabecular outflow capacity and eyes
      with increased resistance in the trabecular meshwork that are prone to pressure
      peaks and deterioration to glaucoma.

PMID- 17458788
TI  - [Early-onset esotropia operated before the age of 24 months: long-term results of
      Cupper's retropexy combined with simultaneous recession of both medial recti].
AB  - BACKGROUND: When and how to operate an early-onset esotropia (onset before 6
      months of age) is still controversial. We conducted a retrospective study of such
      patients operated before the age of 24 months. PATIENTS AND METHODS: 82 patients
      were operated by one surgeon (GK) and followed by the same team. At 5 years post
      operation, evaluation criteria included the residual angle of deviation, visual
      acuity (Birkhauser Nr 505, 5 m) and binocularity (Lang stereotest I, Bagolini
      glasses). RESULTS: At 5 years, the residual angle was excellent (0 degrees to + 5
      degrees ) in 67 % good, (>+5 degrees to +10 degrees or 0 to -5 degrees ) in 23 %,
      and poor (>+10 degrees or <-5 degrees ) in 10 %. During the 5 years of follow-up
      the rate of reoperation was 9.7 %. Isoacuity was obtained in 62 %, slight
      amblyopia (2 lines of interocular difference) was present in 32 %, and average
      amblyopia (> 3 lines of interocular difference) was noted in 6 %. Simultaneous
      perception was present in 53 %, whereas one eye was suppressed or results were
      undetermined in 47 %. No patient demonstrated stereoscopy using the Lang's
      stereotest I. CONCLUSION: The results from our study demonstrate that early
      surgery of early-onset esotropia has a favourable outcome on both visual acuity
      and the residual angle of strabismus. Simultaneous perception was achieved in 53
      %. These figures are comparable to the results of the ELISSS multicentric study.

PMID- 17458789
TI  - Comparison of performance and patient satisfaction of two types of ERG
      electrodes.
AB  - BACKGROUND: An age-controlled comparison concerning patient satisfaction and
      electrical performance of microfibres (DTL) and rigid contact lens (Henkes)
      corneal ERG electrodes was carried out. METHODS: 36 test persons underwent
      complete ophthalmological examination and were equally distributed into 3 age
      groups. Electroretinograms were recorded according to ISCEV standards. Randomly,
      in one eye a Henkes electrode was used and in the other eye a DTL electrode.
      Amplitudes of a- and b-waves and implicit times were measured and compared for
      the two electrode types. RESULTS: 34 of 36 test persons preferred DTL electrodes.
      Electrical performance concerning b-wave amplitudes was comparable. Statistically
      significant differences were detected only for scotopic combined cone-rod
      stimulation in the age groups 20 - 40 and 41 - 60 years between the different
      electrodes. Other recordings did not show differences. A statistically
      significant reduction of signal amplitudes with age was detected for scotopic
      isolated rod signals and combined cone-rod signals. Significance level was p <
      0.05. No conjunctival or corneal erosions were found after ERG recordings for
      either electrode. CONCLUSIONS: Electrical performance is comparable between
      electrodes. For scotopic stimulations age was a significant influencing factor
      for signal amplitude and should be respected for normative values. DTL electrodes
      were preferred by the vast majority of patients. No adverse clinical effects were
      observed for either electrode. DTL electrodes should be preferred due to hygienic
      reasons (single use) and patient comfort.

PMID- 17458790
TI  - [Periocular sub-tenon triamcinolone acetonide injections for the treatment of
      retinal angiomatous proliferation (RAP) and occult choroidal neovascularisation].
AB  - BACKGROUND: Intravitreal triamcinolone injections are used for the treatment of
      occult choroidal neovascularisations (CNV) combined with photodynamic therapy
      (PDT). However, this therapy is not without considerable risks. The periocular
      mode of application seems to be a logical alternative. PATIENTS AND METHODS: A
      retrospective case series of 39 eyes with occult CNV either with retinal
      angiomatous proliferations (RAP) (group A) or with occult choroidal
      neovascularisation (CNV) (group B), treated with periocular triamcinolone was
      reviewed. Data regarding efficacy and side effects were extracted. RESULTS: After
      a mean follow-up of 10 - 11 months 84 % in group A lost < 3 lines of visual
      acuity (VA). 26 % of them gained > or = 1 line of VA. 16 % lost > or = 3 lines of
      VA. In group B (19 eyes) VA was stable in 100 %, whereas 20 % gained > or = 1
      line. Both groups showed similar results for magnification requirement (MR). A
      rise in intraocular pressure was found in 15 %. CONCLUSION: In patients with RAP
      or occult CNV sub-tenon injections seem to delay moderate to severe visual loss.
      Whether larger randomised controlled studies regarding this treatment are still
      relevant in the era of anti-VEGF treatments remains to be seen.

PMID- 17458791
TI  - [Pseudomelanomas of the choroid].
AB  - BACKGROUND: The aim of this study was to evaluate what are the most frequent
      ocular diseases that were suspected for choroidal melanoma ("pseudo melanoma").
      PATIENTS AND METHODS: The data of all patients who were seen in the University
      Hospital of Mainz under the suspicion of choroidal melanoma between 1.1.1994 and
      1.1.2004 and underwent ultrasound examination, fluorescein angiography or fundus
      photography, were analysed retrospectively. Among 458 examined eyes a choroidal
      melanoma was diagnosed in 212 cases. In 246 cases the diagnosis was
      "pseudomelanoma". RESULTS: The most frequent ocular diseases suspected for
      choroidal melanoma were "suspicious nevi" in 31 % of the cases and "disciforme
      macula degeneration" in 34 %. Less frequently we found hyperplasty of pigment
      epithelium (5 %), melanocytoma (10 %), choroidal haemangioma (6 %), choroidal
      detachment (7 %) and retinal macroaneurysma with epi-/subretinal haemorrhages (3
      %). Rare diagnoses were orbital tumour, scleritis posterior and a combined
      hamartoma of retina and pigment epithelium (4 % at all). In 58 eyes without a
      fundus view, ultrasound revealed an intraocular tumour. In these cases
      vitrectomy/cataract extraction was performed and we found a choroidal melanoma in
      5 eyes, a disciforme macula degeneration in 48 eyes and in 5 eyes a retinal
      macroaneurysma. CONCLUSIONS: Age-related macula degeneration (AMD) is the cause
      for one third of all pseudomelanomas. Because of its increasing incidence in the
      future, more attention must be paid to AMD in the differential diagnosis of
      chorioretinal lesions suspicious of melanoma.

PMID- 17458792
TI  - First clinical experience with anecortave acetate (Retaane).
AB  - BACKGROUND: Anecortave acetate is an angiostatic cortisene which is injected as a
      posterior juxtascleral depot and has been shown to be effective in the treatment
      of exudative age-related macular degeneration (AMD). The compound is not yet
      approved in Switzerland but can be used as "compassionate use" in individual
      cases. PATIENTS AND METHODS: An uncontrolled case series with standardised
      documentation of ETDRS visual acuity, near acuity, need for magnification and
      fluorescein angiography was performed. RESULTS: 22 eyes of 19 patients (8 male,
      11 female, average age 78.8 years) were treated with a posterior juxtascleral
      depot injection (PJD) of 15 mg anecortave acetate. The mean change in visual
      acuity after 3 months in eyes treated with anecortave acetate was -2.6 ETDRS
      letters corresponding to 0.52 Snellen lines. 3/20 eyes gained more than 1 line.
      11/20 eyes showed stable visual acuity (+/- 1 Snellen line, +/- 5 ETDRS letters).
      5/20 eyes developed moderate vision loss (one to two Snellen lines, 6-10 ETDRS
      letters). 1/20 lost 18 ETDRS letters (> 3 Snellen lines). There were no moderate
      or severe adverse events. CONCLUSIONS: A PJD of 15 mg anecortave acetate is safe
      and well tolerated. In eyes with occult CNV without recent progression or with
      residual neovascular activity after photodynamic therapy anecortave acetate may
      be an alternative therapeutic option before considering intravitreal anti-VEGF
      agents due to the much less invasive character and lower risk profile.

PMID- 17458793
TI  - [Radial optic neurotomy (RON) for central retinal vein occlusion].
AB  - BACKGROUND: Compression in the lamina cribrosa is discussed as a reason for
      central retinal vein occlusion. Radial optic neurotomy should release the
      pressure and increase venous blood outflow. PATIENTS AND METHODS: In a clinical
      trial 27 eyes with central retinal vein occlusion (22 eyes with clinical
      ischaemia, 5 eyes with continuous disc oedema and visual acuity below 4/10)
      underwent surgical decompression by vitrectomy and radial optic neurotomy. During
      surgery the intravenous pressure in the central vein was tested by infusion
      dynamometry before and right next to the incision. Follow up-time minimally was
      1.5 years. RESULTS: Infusion dynamometry demonstrated a decrease of the central
      vein pressure right next to the incision in all eyes. In 17/22 eyes with
      ischaemic type of occlusion 6 weeks after surgery the relative afferent pupillary
      defect was lowered significantly and no growth of neovascularisations occurred. 5
      eyes with persistence of the afferent pupillary defect received
      laser/cryocoagulation because of neovascularisations. After surgery visual acuity
      improved in 20/27 eyes and remained unchanged in 4/27 eyes. As complications we
      saw small subretinal haemorrhages at the neurotomy site (5/27), vitreous
      haemorrhages (7/27), hypotonia and choroidal detachment (1/27) and segmental
      visual field loss (14/27). CONCLUSIONS: The results of infusion dynamometry
      strongly support the hypothesis of a postulated compression of the central
      retinal vein in the lamina cribrosa. Functional results of radial optic neurotomy
      are superior to those of the natural course of ischaemic retinal vein occlusion
      in the literature, but visual field defects in association with the neurotomy
      site seem to be a serious side-effect of this therapeutic approach.

PMID- 17458794
TI  - [Does cataract surgery increase the risk of exudative age-related macular
      degeneration? Results from a large retrospective case-control study].
AB  - BACKGROUND: Many epidemiological studies indicate a positive correlation between
      cataract surgery and the subsequent progression of age-related macular
      degeneration (AMD). Such a correlation would have far-reaching consequences.
      However, in epidemiological studies it is difficult to determine the significance
      of a single risk factor, such as cataract surgery. PATIENTS AND METHODS: We
      performed a retrospective case-control study of patients with new onset exudative
      age-related macular degeneration to determine if cataract surgery was a
      predisposing factor. A total of 1496 eyes were included in the study: 984 cases
      with new onset of exudative AMD and 512 control eyes with early signs of age
      related maculopathy. Lens status (phakic or pseudophakic) was determined for each
      eye. RESULTS: There was no significant difference in lens status between study
      and control group (227/984 [23.1 %] vs. 112/512 [21.8 %] pseudophakic, p =
      0.6487; OR = 1.071; 95 % CI = 0.8284-1.384). In cases with bilateral pseudophakia
      (n = 64) no statistically significant difference of the interval between cataract
      surgery in either eye and the onset of exudative AMD in the study eye was found
      (225.9 +/- 170.4 vs. 209.9 +/- 158.2 weeks, p = 0.27). CONCLUSIONS: Our results
      provide evidence that cataract surgery is not a major risk factor for the
      development of exudative AMD.

PMID- 17458795
TI  - Pars plana vitrectomy with 25-gauge instruments in the treatment of idiopathic
      epiretinal membranes.
AB  - BACKGROUND: The sutureless pars plana vitrectomy (ppv) using a 25-gauge
      instrumentation is a minimally invasive technique which is mainly performed for
      procedures that do not require extensive vitreous dissection. In a consecutive
      case series with retrospective collection of data, the advantages and the risks
      of this technique are discussed in comparison with the conventional 20-gauge ppv
      for patients with idiopathic epiretinal membranes. PATIENTS AND METHODS: Between
      July 2003 and November 2004, 64 consecutive patients (26 men, 38 women, mean age:
      72 years) were treated with a 20-gauge ppv, and between December 2004 and January
      2006, 75 consecutive patients (42 men, 33 women, mean age: 70.4 years) were
      treated with a 25-gauge ppv. The patients were classified into three groups: ppv
      combined with phacoemulsification (group 1), ppv in pseudophakic eyes (group 2),
      or ppv without phacoemulsification (group 3). There were postoperative controls
      after at least 1, 30 and 180 days. RESULTS: The visual acuity improves quicker in
      the groups 1 and 2 of the 25-gauge ppv compared with the 20-gauge ppv due to less
      postoperative inflammation and to the practical absence of postoperative
      astigmatism. In the group 3, after using either a 25-gauge or a 20 gauge ppv, the
      development of a postoperative cataract restrained the improvement of the visual
      acuity. The following postoperative complications were noticed using the 25-gauge
      ppv: transitory hypotonia with an eye pressure < 5 mmHg (9 cases) and with
      attendant choroidal detachment (3 cases), macular oedema (1 case), and
      endophthalmitis (1 case); using the 20-gauge ppv: transitory hypertonia (9
      cases), macular oedema (2 cases), and retinal detachment (3 cases). CONCLUSIONS:
      The sutureless 25-gauge ppv is advantageous for a quick postoperative recovery of
      the visual acuity, and may be well combined with cataract surgery. Nevertheless,
      this technique involves risks and its further evaluation, especially in
      comparison using a 23-gauge ppv, is indicated.

PMID- 17458796
TI  - Intravitreal triamcinolone acetonide for serous retinal pigment epithelial
      detachments in exudative age-related macular degeneration.
AB  - BACKGROUND: Due to the high risk of RPE tears PDT is usually not performed in
      eyes with serous RPE detachments (sRPED). For this reason this subform of
      exudative AMD was so far untreatable. PATIENTS AND METHODS: We report on a
      prospective uncontrolled observational case series. 20 eyes of 20 patients with
      subfoveal sRPED demonstrated by OCT were treated between June 2005 and April 2006
      with intravitreal triamcinolone acetonide (IVTA). In 15 cases there was a primary
      sRPED, in 5 cases it had developed after one or more sessions of photodynamic
      therapy with Visudyne. RESULTS: There was a trend for better average visual
      acuity in the group with primary sRPED from 0.73 logMAR (0.19 Snellen equivalent)
      at baseline (n = 15) to 0.68 logMAR (0.21 Snellen) after one month (n = 15) (p =
      0.19) and to 0.60 logMAR (0.25 Snellen) after three months (n = 14) (p = 0.41).
      The maximal height of sRPED decreased to an average of 35.3 % after one month (n
      = 15) and increased again to 56.9 % after 3 months (n = 14). One patient was lost
      to follow-up. In the group of eyes with sRPED after PDT, one eye developed an RPE
      tear with severe vision loss two weeks after IVTA. In the remaining four eyes
      average visual acuity improved from 0.90 logMAR (0.13 Snellen) at baseline to
      0.73 logMAR (0.19 Snellen) after one month and to 0.80 logMAR (0.16 Snellen)
      after 3 months. Complete resolution of sRPED was observed in 8/20 eyes (4/5 eyes
      with sRPED after PDT and 4/15 eyes with primary sRPED). CONCLUSIONS: IVTA seems
      to be a therapeutic option in otherwise untreatable eyes with sRPED.

PMID- 17458797
TI  - Autologous serum application in the treatment of Mooren's ulcer.
AB  - BACKGROUND: Mooren's ulcer is a peripheral corneal ulceration of presumed
      autoimmune aetiology. Its clinical course and eventual prognosis is variable and
      usually these ulcers respond poorly to conventional therapy. HISTORY AND SIGNS: A
      67-year-old male was referred to our hospital for a painful, red and tearing left
      eye after receiving debris. Slit-lamp examination revealed a 3.2 x 2.1 mm
      peripheral corneal ulcer, a diffuse thinning of the lateral limbus (between 3
      o'clock and 5 o'clock) and some endothelial precipitates. The conjunctiva was
      severely congested. In the anterior chamber, cells (++) and fibrin were found.
      THERAPY AND OUTCOME: We introduced an antibiotic, corticosteroid and cyclosporin
      therapy to treat the marginal corneal deficit caused by Mooren's ulcer. The
      patient did not respond to the initial treatment, but re-epithelialisation
      occurred and the corneal deficit improved after the introduction of autologous
      serum eye drops. CONCLUSION: Autologous serum seems to be an effective
      supplementary therapy in Mooren's ulcer.

PMID- 17458798
TI  - Clinical findings in patients with topical anaesthetic abuse keratitis: a report
      of five cases.
AB  - PURPOSE: The purpose of this study is to describe the clinical findings in five
      patients with topical anaesthetic abuse. PATIENTS: Five patients presented in the
      emergency department with persistent corneal epithelial defects associated with a
      ring infiltrate in the corneal stroma, without any referred history of ocular
      trauma or ocular application of any corrosive or alkali substance. The patients
      were hospitalised and a thorough ocular examination was accomplished. Systemic
      evaluation and psychiatric consultation were also done. RESULTS: A detailed
      history in all our patients revealed topical anaesthetic abuse keratitis. The
      topical anaesthetic was deliberately taken from the pharmacy without medical
      prescription. In all our patients a psychiatric disease and/or drug abuse was
      disclosed after psychiatric examination. The hallmark of topical anaesthetic
      abuse keratitis was a persistent corneal epithelial defect and a complete or
      incomplete ring infiltration of the corneal stroma in all cases. Functional and
      anatomic results after the appropriate treatment were not favourable in the
      majority of the cases, leading in some of them to blindness. CONCLUSIONS:
      Although topical anaesthetic abuse keratitis is rare, it should be considered in
      the differential diagnosis when we see a patient with a persistent corneal
      epithelial defect together with a ring infiltration on the corneal stroma.
      Psychiatric diseases and/or systemic drug abuse are usually associated with this
      toxic keratopathy. The psychiatric diseases that accompany this toxic keratopathy
      may also lead to death or to severe handicap as a result of suicide attempts by
      the patients. Psychiatric consultation and therapy are imperative in the
      management of such patients.

PMID- 17458799
TI  - [Posterior chamber intraocular lens in the anterior chamber].
AB  - BACKGROUND: The choice of design for intraocular lenses (IOLs) mainly depends on
      the selected location for the implant. HISTORY AND SIGNS: We report the case of
      dislocation of a foldable open-loop posterior chamber IOL into the anterior
      chamber during retinal detachment surgery. After several vitreoretinal
      interventions visual acuity was hand movements. THERAPY AND OUTCOME: The IOL
      remained in the anterior chamber without complications such as IOP rise or
      endothelial decompensation for several years. CONCLUSIONS: Foldable open-loop
      posterior chamber IOLs can be left in suitable anterior chambers for years
      without complications such as rise of intraocular pressure or corneal endothelial
      damage. Repeated measurements of endothelial cell density can provide an
      informative basis for the operative removal of this lens.

PMID- 17458800
TI  - Bartonella henselae infection presenting as a unilateral acute maculopathy.
AB  - BACKGROUND: The purpose of this article is to report an unusual ocular
      manifestation of cat scratch disease (CSD) presenting as a unilateral acute
      maculopathy (UAM). We describe and review the clinical, laboratory, fluorescein
      angiography (FA), indocyanine green angiography (ICG) and optical coherence
      tomography (OCT) records of a patient with CSD. HISTORY AND SIGNS: A 30-year-old
      Chinese woman presented with a painless progressive visual loss affecting her
      left eye. Fundus examination of the left eye disclosed rare vitreous cells and a
      deep-creamy choroidal macular lesion with satellite foci of choroiditis. THERAPY
      AND OUTCOME: FA revealed an early hypofluorescence of the lesion, becoming
      progressively hyperfluorescent with a leakage on the late phase. The ICG
      disclosed an early hypofluorescence of the macular lesion with a mild staining of
      its periphery on the late frames. Hypofluorescent satellite lesions were visible
      both on the early and late frames. The OCT disclosed a serous retinal detachment
      at the level of the whitish lesion. Serologies for Bartonella henselae (BH)
      became positive (IgG 1: 512, IgM < 1:20) confirming an active or recent
      infection. CONCLUSIONS: Ocular manifestations of CSD can appear as a UAM with
      satellite lesions. CSD should be ruled out in patients manifesting such clinical
      features.

PMID- 17458801
TI  - Protracted Aspergillus versicolor endophthalmitis caused by corneal
      microperforation.
AB  - BACKGROUND: Here we describe the characterization of a protracted Aspergillus
      versicolor endophthalmitis caused by a corneal microperforation. HISTORY AND
      SIGNS: A 58-year-old patient noticed blurred vision two weeks after he was hit in
      the eye by an old cable in a dilapidated house. A traumatic cataract and an
      intraocular inflammation were diagnosed and treated elsewhere with
      phacoemulsification and anti-inflammatory drugs. Vitreous samples were sterile.
      Despite topical steroids visual acuity continued to decrease and the patient
      presented in Lausanne 6 months later with a visual acuity of counting fingers,
      major inflammation of the anterior segment and a small corneal scar. Fundus
      examination revealed massive vitreous inflammation with a voluminous whitish
      chorioretinal infiltrate temporally. THERAPY AND OUTCOME: Vitrectomy with
      dissection of a protuberant epiretinal filamentous tissue in the temporal fundus
      was performed, and Amikacine, Vancomycine and Amphothericine were injected
      intravitreally. Bacteriological work-up revealed Aspergillus versicolor. Visual
      acuity improved to 0.2 with topical steroids and oral antifungal drugs.
      CONCLUSIONS: Corneal microperforations may cause a protracted endophthalmitis due
      to Aspergillus versicolor, a rare fungus, which is commonly found in insulation
      materials and cables in dilapidated houses.

PMID- 17458802
TI  - Uveal effusion syndrome.
AB  - BACKGROUND: The idiopathic uveal effusion syndrome is characterized by a
      spontaneous serous detachment of the choroid and ciliary body. Pathophysiology is
      related to a relative scleral impermeability to protein. A possible complication
      is the development of a serous retinal detachment. HISTORY AND SIGNS: We present
      a 65-year-old male, mild hyperopic patient with a peripheral circular choroidal
      tumour OD, and macular retinal folds OU. Visual acuity was OD 0.5 due to an
      additional cataract and OS 1.0. Ocular inflammation was not present. Extensive
      medical, serological and immunological investigations were normal. On MRI a
      thicker sclera compatible with the diagnosis was measured. THERAPY AND OUTCOME:
      Twelve months after the first presentation the patient has no complaints and the
      ocular findings are stable so that a therapy was not necessary up to now.
      CONCLUSIONS: Uveal effusion syndrome is a rare disease which belongs to the
      differential diagnosis of choroidal tumour with serous retinal detachment. The
      correct diagnosis is important as sclerectomy or sclerotomy may be an effective
      treatment.

PMID- 17458803
TI  - Retrobulbar blood flow in idiopathic dilated episcleral veins and glaucoma.
AB  - BACKGROUND: Dilated episcleral veins may occur in the presence of orbital tumors,
      carotid cavernous sinus fistula and other orbital obstructive lesions. HISTORY
      AND SIGNS: A 39-year-old man had a history of a red left eye for two years. The
      visual acuity was 20/20, episcleral and conjunctival veins were dilated, and both
      the intraocular (24 mmHg) and episcleral venous (18 mmHg) pressures were
      increased. The canal of Schlemm was filled with blood, and glaucomatous damage
      was pronounced in the optic nerve head and the visual field of the left eye. The
      retrobulbar blood flow in the left eye was normal in the ophthalmic and central
      retinal arteries, but markedly decreased in the central retinal vein. There were
      no signs of fistula or shunts. The right eye was without any pathology. MR and
      catheter angiography of the head and orbit were both normal. THERAPY AND OUTCOME:
      Following trabeculectomy, the intraocular and episcleral venous pressures dropped
      to 9 mmHg and 8 mmHg, respectively, at 6 months follow-up. The episcleral and
      conjunctival venous congestion regressed, and the blood flow in the central
      retinal vein increased. CONCLUSION: The reason for the observed clinical picture
      (Radius-Maumenee syndrome) and haemodynamic improvement after reduction of the
      intraocular pressure is not clear. We outline a hypothesis involving an increase
      of the vascular resistance in the vortex veins and the superior ophthalmic vein
      with a shift in local blood volume and vascular pressure due to high intraocular
      pressure.

PMID- 17458804
TI  - Ultrasound biomicroscopy evaluation of angle closure in a patient with multiple
      and bilateral iridociliary cysts.
AB  - PURPOSE: The aim of this study was to describe the findings of ultrasound
      biomicroscopy (UBM) in a case with bilateral, multilobulate primary iridociliary
      cysts presenting as chronic angle-closure glaucoma. HISTORY AND SIGNS: An 82-year
      old woman was admitted to a tertiary ophthalmological centre for a thorough
      exploration of the gradual deterioration of her visual fields and optic discs.
      Clinical evaluation of the patient revealed angle-closure glaucoma and cataract
      in both eyes. The use of UBM disclosed the presence of bilateral, multilobulate
      iridociliary cysts in all quadrants. The presence of multiple and bilateral
      iridociliary cysts was the cause of iris anterior displacement and the subsequent
      angle closure in this patient. CONCLUSIONS: Primary iridociliary cysts may rarely
      progress to a size that can compromise the angle. They are usually considered as
      benign and stationary lesions. The advent of UBM is an invaluable tool for the
      contemporary ophthalmologist in order to set the diagnosis and follow the
      evolution of those lesions.

PMID- 17458805
TI  - [Excessive tearing due to decentred progessive eyeglasses].
AB  - BACKGROUND: The eye and the progressive lenses in eyeglasses form a three
      dimensional optical system, which must be well matched. PATIENT: A 71-year-old
      man complained about a new and unusual tearing and scratching sensation in his
      eyes. The work-up revealed subnormal values of the Schirmer test, from the eye
      refraction of different eyeglass powers and strongly decentred progressive lenses
      in his, just a few-months-old, eyeglasses. THERAPY AND OUTCOME: A lubricating
      therapy remained without success. However, the use of new and correct eyeglasses
      eliminated the symptoms. CONCLUSION: Tearing and the sensation of scratching in
      the eyes in this case are symptoms of an eyeglasses-induced asthenopia.
      Consequently, it may pay to control the eyeglasses and the centration of
      progressive lenses in cases with unclear, unspecific eye symptoms even without
      dissatisfaction with eyeglasses.

PMID- 17458806
TI  - [Surgical treatment of diplopia in Graves' orbitopathy].
AB  - BACKGROUND: The correction of oculomotor disorder in Grave's disease is applied
      on pathological extraocular muscles. Based on the global muscular restriction
      (bilateral forced duction test) and angular measurements, we have used a non
      adjustable technique. PATIENTS AND METHODS: We performed a retrospective analysis
      of 21 patients (23 operations) with thyroid-associated orbitopathy operated for
      persisting diplopia. The angles of deviation in the 9 diagnostic directions of
      gaze and the field of binocular vision were measured with the Harm's tangent
      scale before and after surgery. Sixteen patients were operated only on vertical
      muscles. The mean follow-up was 45 months. RESULTS: 76 % of the patients (95 %
      confidence interval [CI], 58-94 %) obtained a large and centred field of
      binocular vision without prisms. 14 % (95 % CI, 0-29 %) had binocular vision with
      the use of prisms. Diplopia persisted in one patient despite 3 operations. Taking
      into consideration the interventions done before the patient was referred to us,
      the reintervention rate was 13 % (95 % CI, 0-28 %). CONCLUSIONS: A binocular
      field of vision can be successfully restored in the majority of patients with
      Graves' orbitopathy, using a non-adjustable surgical technique.

PMID- 17458807
TI  - Unusual cause of bilateral optic disc swelling: POEMS syndrome.
AB  - BACKGROUND: POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy,
      Monoclonal protein, Skin changes) is a rare disorder associated with plasma cell
      disorder. Optic disc swelling can be present, and macular oedema has been
      reported once before. PATIENTS AND METHODS: Three patients with POEMS syndrome
      were investigated. Lumbar puncture and neuro-ophthalmic examination were
      performed on all patients. RESULTS: Visual symptoms included decreased vision,
      photopsia and blurred vision. Optic disc swelling was present in all three
      patients. Visual acuity was decreased in only one patient (0.2 in right eye, 0.7
      in left eye) due to macular oedema, and another patient with normal visual acuity
      showed also a mild macular oedema on fluorescein angiography. In these two
      patients, elevated intracranial pressure was found (30 and 39 cm H(2)O,
      respectively). The macular oedema disappeared under steroids and acetazolamide
      therapy with visual improvement, but optic disc swelling remained. CONCLUSION:
      Optic disc swelling is frequent in POEMS and macular oedema may be more
      frequently present than previously thought. Interestingly macular oedema was
      detected in the two patients with increased intracranial pressure.

PMID- 17458808
TI  - Bilateral sequential optic neuropathy as the initial manifestation of Sjogren
      syndrome.
AB  - BACKGROUND: Neuro-ophthalmic findings are uncommon in the setting of Sjogren
      syndrome. We report the case of a patient with bilateral, sequential optic
      neuropathy as the initial manifestation of Sjogren syndrome. HISTORY AND SIGNS: A
      38-year-old male presented with sudden painless visual loss in his left eye in
      May 2005. Fundus examination revealed a left swollen optic disk. Magnetic
      resonance imaging (MRI) revealed a left optic nerve lesion. Elevated titres of
      autoantibodies (ANA, anti-SSA, anti-SSB) were found, suggestive of Sjogren
      syndrome. In January 2006, he presented with painful sudden visual loss in the
      right eye. Fundus examination revealed a right swollen optic disk and left optic
      nerve atrophy. MRI was normal. Other aetiologies were ruled out. THERAPY AND
      OUTCOME: Each episode was treated with intravenous methylprednisolone (1 g/day
      during 3 days), followed by oral prednisone (1 mg/kg/day). Moderate improvement
      of vision ensued in both eyes. CONCLUSIONS: Atypical presentation of an optic
      neuropathy must raise the suspicion of an unusual aetiology. Our case illustrates
      how a bilateral sequential optic neuropathy in an otherwise healthy patient can
      result from an unusual inflammatory aetiology: primary Sjogren syndrome.

PMID- 17458809
TI  - Patient with Fanconi Syndrome (FS) and retinitis pigmentosa (RP) caused by a
      deletion and duplication of mitochondrial DNA (mtDNA).
AB  - BACKGROUND: We report a patient with a highly unusual presentation of a
      mitochondrial disorder. HISTORY AND SIGNS: An 8-year old girl presented with
      muscular cramps as well as height and weight deceleration. Investigations
      revealed lactic acidosis, electrolytic imbalance and urinary loss of glucose and
      electrolytes secondary to proximal renal tubulopathy consistent with Fanconi
      syndrome (FS). Ophthalmic examination revealed asymptomatic retinitis pigmentosa
      (RP) with no other ocular manifestations. A mitochondriopathy was suspected and
      genetic analysis performed. THERAPY AND OUTCOME: Southern blotting documented a
      heteroplasmic mutation of mtDNA with deletion/duplication. Three discrete
      mitochondrial genomes were detected: normal; deletion of 6.7 kb and a
      deletion/duplication consisting of 1 normal and 1 deleted genome. The relative
      proportions varied considerably between tissues. CONCLUSIONS: The association of
      FS and RP combines features of Kearns-Sayre syndrome and Pearson marrow-pancreas
      syndrome, without being typical of either. This highly unusual clinical
      presentation emphasises the need for systemic investigation of patients with FS
      and further underlines the importance of mtDNA analysis in patients with
      unexpected associations of affected tissues.

PMID- 17458810
TI  - [Juvenile cataract associated with microcornea and glucosuria: a new syndrome].
AB  - BACKGROUND: Predisposition is responsible for approximately 50% of age-related
      cataracts. Investigation of inherited forms of cataract provides the opportunity
      to identify the genes that may play a role in age-related cataract as well.
      PATIENTS AND METHODS: We describe the phenotype of a Swiss family with juvenile
      cataract, associated with microcornea and renal glucosuria. 11 of 17 family
      members in three generations underwent ophthalmic assessment and urine analysis.
      Medical records or questionnaires were evaluated in the remaining six cases.
      RESULTS: Eleven family members had progressive juvenile cataract. Eight affected
      members available for clinical examination had bilateral microcornea, not
      associated with microphthalmos. Furthermore, renal glucosuria was demonstrated in
      six of these persons. The mode of inheritance is autosomal-dominant. CONCLUSIONS:
      We have defined a new syndrome, consisting of the association of juvenile
      cataract, microcornea and renal glucosuria. The pattern of inheritance is
      autosomal-dominant. Genotyping is ongoing.

PMID- 17458811
TI  - [Iris granulomas of unknown aetiology].
AB  - BACKGROUND: Non-pigmented tumours of the iris are rare and their clinical
      classification can be difficult, especially in the absence of systemic
      manifestations. HISTORY AND SIGNS: We report the case of a unilateral vascular,
      non-pigmented iris tumour in a 47-year-old patient. Clinically, the iris lesion
      showed progressive growth and tumour vascularisation. THERAPY AND OUTCOME: A
      systemic work-up failed to reveal any underlying systemic disease. Biopsy showed
      a non-necrotising granuloma. The lesion responded well to systemic corticosteroid
      therapy. CONCLUSIONS: Isolated granulomas of the iris are rare and clinically
      often indistinguishable from malignant tumours like melanoma. Due to the clinical
      course and the regression under corticosteroid therapy we concluded that this
      iris granuloma may be an isolated ocular manifestation of sarcoidosis.

PMID- 17458812
TI  - Interferon-associated retinopathy--a case report.
AB  - BACKGROUND: Interferon alpha is used for treatment in oncology and for chronic
      hepatitis C. Interferon-associated retinopathy is not infrequent and typically
      includes cotton wool spots, haemorrhages, rarely macular or papillary oedema,
      capillary non-perfusion and sometimes retinal or even choroidal vascular
      occlusion. The latter may be irreversible, while uncomplicated forms are usually
      reversible. We report an atypical case of interferon-associated retinopathy,
      associated with microaneurysms, Roth spots, and retinal pigment changes. HISTORY
      AND SIGNS: A 63-year-old asymptomatic patient presented with partially white
      centred, flame-shaped haemorrhages, some cotton wool spots and microaneurysms on
      both fundi. In addition, the left eye presented chronic pigment epithelium
      abnormalities surrounding the fovea without signs of exudation, most likely
      secondary to a previous central retinal exudative detachment combined with
      choroidal hypoperfusion. Interferon alpha 2a therapy for chronic hepatitis C had
      been given for 6 months. He was known for arterial hypertension (risk factor),
      mild microcytic anaemia and mild glucose intolerance, which may be responsible
      for some unusual features of the retinopathy. THERAPY AND OUTCOME: The patient
      was closely followed, while the interferon therapy was continued on reduced
      dosage. No vision-threatening complication was observed. CONCLUSIONS: Interferon
      associated retinopathy may show atypical features. Early diagnosis and careful
      follow-up are recommended in order to avoid progression to irreversible changes.
      Dose-reduction or even interruption of interferon treatment needs to be
      considered in cases of interferon-associated retinopathy.

PMID- 17458813
TI  - Combination therapy of PDT and triamcinolone in CNV associated with fundus
      flavimaculatus.
AB  - BACKGROUND: Photodynamic therapy (PDT) performed in this rare condition showed
      promising results according to 3 other case reports. HISTORY AND SIGNS: A 47-year
      old female patient with fundus flavimaculatus developed metamorphopsia and
      minimal vision deterioration (20/25) in her left eye. Fluorescein angiography
      revealed all signs of classic choroidal neovascularisation (CNV). THERAPY AND
      OUTCOME: After the first PDT treatment with a spot adapted to the size of the
      juxtafoveal CNV (1.5 mm) and standard parameters visual acuity (VA) dropped to
      20/63, more leakage and progression to subfoveal CNV was observed. 3 months after
      the second PDT VA was 20/80 and FA revealed persistent leakage. Given the results
      of the combination treatment in age-related macular degeneration and the poor
      outcome seen after PDT alone in this case, PDT and intravitreal injection of 4 mg
      triamcinolone acetonide on the same day was applied. 3, 6 and 9 months after
      treatment VA stabilised at 20/63 and FA showed confirmed regression of the CNV
      and, thus, no leakage, but scarring. CONCLUSIONS: To the best of our knowledge
      this is the first published report of CNV secondary to fundus flavimaculatus in
      which PDT alone failed to stop leakage and progression of the CNV. However
      therapy combined with triamcinolone acetonide was successful.

PMID- 17458814
TI  - Pars Plana vitrectomy and epiretinal membrane peeling for vitreoretinal traction
      associated with combined hamartoma of the retina and retinal pigment epithelium
      (CHRRPE).
AB  - BACKGROUND: Combined hamartoma of the retina and retinal pigment epithelium
      (CHRRPE) are rare, benign tumours that typically appear slightly elevated and are
      characterised by varying amounts of pigmentation, vascular tortuosity, and
      epiretinal membrane formation that can be related to macular distortion. The
      importance of changes at the vitreoretinal interface in this condition as a risk
      for visual loss was early recognised but controversy exists concerning the
      benefits of surgical removal of the tractional component. We describe 2 cases of
      CHRRPE who demonstrated significant visual acuity improvement after pars plana
      vitrectomy and epiretinal membrane peeling. HISTORY AND SIGNS: A 12-year-old girl
      and a 14-year-old boy presented with progressive unilateral visual loss related
      with a CHRRPE. In both instances the hamartoma was associated with a thickened
      posterior hyaloid and epiretinal membrane inducing considerable vitreomacular
      traction as shown by optical coherence tomography (OCT). Best-corrected pre
      operative visual acuity was 0.2 in both cases. THERAPY AND OUTCOME: Vitrectomy
      and epiretinal membrane peeling were performed in both cases. Relief of
      vitreomacular traction and macular distortion was achieved and documented on OCT.
      Visual acuity at the latest follow up was 0.5 and 0.8, respectively. CONCLUSIONS:
      Surgical dissection can be effective in the treatment of vitreomacular traction
      associated with CHRRPE with a good functional and anatomical outcome.

PMID- 17458815
TI  - Retinal detachment in patients with acute retinal necrosis: a case series.
AB  - BACKGROUND: Acute retinal necrosis is a rare and severe infectious ocular disease
      frequently complicated by retinal detachment. PATIENTS AND METHODS: Records of
      six consecutive eyes from five patients with acute retinal necrosis were
      reviewed. RESULTS: PCR analysis of intraocular fluids was positive for Varizella
      zoster virus, Herpes virus 1 or 2. Treatment consisted of systemic acyclovir,
      systemic and local corticosteroids as well as aspirin. Progression of the
      necrosis could be effectively controlled, however all eyes developed retinal
      detachment within 55 +/- 24 days. Retinal surgery including pars plana
      vitrectomy, encircling scleral buckling, liquid silicone or gas filling led to
      retinal reattachment in all patients during the follow-up time (590 +/- 242
      days). The mean visual acuity at the end of the follow-up time was 0.4 +/- 0.3.
      CONCLUSIONS: The diagnosis of acute retinal necrosis is reliably confirmed using
      PCR analysis of intraocular fluids. Currently available treatments are effective
      in stopping progression of the necrosis. There is, however, a high risk of
      retinal detachment, which can be successfully treated with vitreoretinal surgery.

PMID- 17458816
TI  - [Vasoproliferative retinal tumors].
AB  - BACKGROUND: Vasoproliferative Tumors of the retina (VPTR) are benign tumors of
      unknown origin, occurring mostly in otherwise systemically healthy patients.
      These highly vascularised tumors are characterised by a pink to yellow colour on
      funduscopy and are usually situated in the inferior part of the retina. They are
      associated with intraretinal hemorrhages, intra- or subretinal exudates and
      hyperpigmentation of the retinal pigment epithelium. MATERIALS AND METHODS: We
      performed a retrospective case review of seven cases which have been diagnosed
      with VPTR between 2004 and 2006 in the Department of Ophthalmology, University
      Hospital Zurich. RESULTS: The median follow up was 8 months (range: 1-24 months).
      We found a presumed underlying cause for the VPTR in 6 out of 7 patients. 3
      patients showed a long standing retinal detachment; in the other 3 there was an
      untreated chronic uveitis. In one case the tumour was surgically excised and
      histology was performed. CONCLUSIONS: VPTR of the ocular fundus are a distinct
      entity in the differential diagnosis of intraocular tumors. These benign lesions
      represent reactive gliovascular proliferations, with varying degrees of both
      gliosis and of vascular proliferation. VPTR can be idiopathic, or they develop
      after inflammatory, vascular, traumatic, dystrophic or degenerative ocular
      diseases, in particular, uveitis. The major differential diagnosis includes other
      vascular lesions or tumors of the ocular fundus like capillary retinal
      hemangiomas, Coat' Disease or malignancies. The natural course of VPTR appears to
      be variable. The therapy is based on tumor size, localisation and complications.

PMID- 17458817
TI  - [Options and strategy for the treatment of chronic endogenous uveitis].
AB  - PURPOSE: The treatment of chronic endogenous uveitis has included the use of
      local and systemic corticosteroids since the early 1950 s, and these still
      constitute the first-line option in the treatment, once an infectious aetiology
      has been excluded. METHODS: Since the 1960 s, broad experience has been collected
      with antiproliferative and alkylating agents, and since the 1980 s several
      immunosuppressants have been employed in the therapy for endogenous uveitis. It
      has been recognised that the therapeutic response is not only related to a
      specific uveitic entity, but also to the genetic background of the individual.
      RESULTS: Therefore, no clear guide lines for therapy exist and, for most of the
      drugs, controlled studies are not available. Vitrectomy and intravitreal drug
      delivery have been added as local options on top or in case of failure of
      systemic therapies. The advent of biological agents, however, i. e. the
      introduction of interferon alpha and TNF alpha blocking agents, has opened a new
      era in the treatment of immunogenetic and autoimmune disorders. CONCLUSION:
      Evidence-based knowledge and personal experience have been reviewed to provide an
      update on the therapeutic strategy for chronic endogenous uveitis. The newly
      introduced biologicals seem to represent an interesting addition to the existing
      therapeutic options. Informations pertaining to efficacy and side effects of a
      long-term treatment of uveitis are, nevertheless, as yet not available.

PMID- 17458818
TI  - [Experience in establishing ophthalmology at the Hopital Albert Schweitzer (HAS)
      in Deschapelles, Haiti].
AB  - BACKGROUND: Haiti is regarded as the poorest country of the Western hemisphere.
      The Hopital Albert Schweitzer (HAS), founded in 1956 by Larimer Melon, is
      providing medical care to the Artibonite valley, an area in the centre of Haiti
      with over 400 000 inhabitants. Until 2001, a three-fold population was without
      eye care in central Haiti. HISTORY: In 2001, Hans Rudolf Bracher, a retired
      ophthalmologist from Bern, initiated the eye department at HAS and organised an
      eye examination unit, a microscope and further surgical equipment. Since then,
      eye care to the population was provided by short-term visits of ophthalmologists,
      nurses and orthoptists, mainly from switzerland. Additionally, teaching and
      surgical training was performed at university hospital in Port-au-Price, the only
      education centre for ophthalmologists in the country. PRESENT SITUATION: The
      actual political and security situation complicates visits of western doctors. A
      development association for the HAS eye department was founded and with its help,
      an Haitian ophthalmologist is employed in a full-time position. Furthermore,
      logistic support is provided with drugs and surgical equipment. Today, under
      difficult circumstances, the eye department is well established as an effective
      and cost-covering institution at HAS.

PMID- 17458819
TI  - [Dealing with chronic disease: the need for a therapeutic alliance with the
      patient].

PMID- 17458820
TI  - [Uric acid and hypertension: a non-casual relationship?].

PMID- 17458821
TI  - [Changing ideas about the nephrotic syndrome].

PMID- 17458822
TI  - [Role of vitamin D and its analogues in dialysis patients: beyond PTH control].

PMID- 17458823
TI  - [The cardiorenal syndrome: an emerging renal disease].

PMID- 17458824
TI  - [Cardiovascular risk factors, homocysteine and folates].

PMID- 17458825
TI  - [Immunosuppressive therapy without calcineurin inhibitors for renal transplants?
      Perhaps we should be cautions...].

PMID- 17458826
TI  - [Antiphospholipid syndrome and kidney].
AB  - The diagnosis of antiphospholipid syndrome (APS) relies on clinical and
      laboratory criteria, which have been recently outlined in specific consensus
      conferences. Renal involvement in APS is not infrequent and includes different
      clinical patterns. For clinical purposes a distinction can be made between large
      vessel and microvascular involvement. Renal artery stenosis is frequent in APS.
      In case of microvascular involvement with an acute clinical course a differential
      diagnosis with other thrombotic microangiopathic diseases has to be made, taking
      in account thrombotic thrombocytopenic purpura, hemolytic uremic syndrome,
      malignant hypertension, drug nephrotoxicity (cyclosporin) and others. The disease
      is often chronic, with hypertension, different degrees of renal insufficiency and
      mild proteinuria. In patients with systemic lupus erythematosus and
      antiphospholipid antibodies the prognosis of kidney disease is generally poorer
      than in lupus alone. Finally, the kidney is almost invariably a target in
      catastrophic antiphospholipid syndrome. Anticoagulation is the therapy of choice,
      especially in arterial stenosis and acute disease, but is probably also indicated
      in chronic and subacute patterns. The role of immunomodulatory therapy has to be
      assessed.

PMID- 17458827
TI  - [Acute pyelonephritis in adults].
AB  - Acute pyelonephritis (APN) is a frequent and possibly severe pathological
      condition responsible for more than 100,000 hospitalizations per year in the
      United States. Etiology is prevalently Escherichia coli, and risk factors include
      sexual activity, genetic predisposition, old age and infection via urological
      instrumentation. The exact correlation between APN and vesicoureteral reflux has
      not yet been defined. Diagnosis of APN may be clinical, but examination using
      computed tomography (CT) or nuclear magnetic resonance (NMR) spectroscopy allows
      a more precise definition and may provide evidence of abscesses. Severe cases
      should be treated with a fluoroquinolone or extended-spectrum cephalosporin
      associated or not with aminoglycoside. Treatment should be continued for at least
      10 days. Long-term evolution of APN is still unknown, even if formation of
      cortical scars and possible development of macroalbuminuria or renal failure are
      described. Pregnancy, diabetes and renal transplantation represent situations in
      which APN may be particularly severe. Formation of renal abscesses is
      underestimated and must be evaluated by CT or NMR spectroscopy evaluation.
      Abscesses must be drained only if they are of great size.

PMID- 17458828
TI  - [Pregnancy in chronic dialysis. A case report and a review of the literature].
AB  - A case report of a pregnancy in a patient with end-stage renal disease on chronic
      dialysis is presented. The epidemiological data regarding this rare event and the
      factors influencing and limiting fertility in uremic women are discussed. The
      outcomes of pregnancy in dialysis as reported in national registries and
      literature series are analyzed. For the management of pregnancy in dialysis
      several practical problems have to be dealt with: the type of dialysis,
      sterilization of dialysis materials, dialysis dose, dialysis bath composition,
      extracorporeal circuit anticoagulation, and the diet of the pregnant woman. All
      these issues are discussed, with special attention to solutions facilitating the
      best outcome of pregnancy. Finally, the main complications of both normal and
      uremic pregnancies, anemia and hypertension, are discussed together with the
      solutions proposed in this particular condition.

PMID- 17458829
TI  - [2004 census of the Italian nephrology and dialysis units].
AB  - The Italian Society of Nephrology (SIN) promoted a census of the renal and
      dialysis units to analyze structural and human resources, organizational aspects,
      activities and epidemiological data. An online 158-item questionnaire for the
      year 2004 was used. Three hundred sixty-three public renal units, 303 satellite
      dialysis centers and 295 private dialysis centers were identified, resulting in a
      total of 961 dialysis centers (16.4 per million population, pmp). The inpatient
      renal beds were 2,742 (47 pmp). Renal and dialysis activity was performed by
      3,728 physicians (64 pmp), of whom 2,964 (80%) were nephrologists. There was no
      permanent medical assistance in 41% of the satellite dialysis centers. Renal
      admissions (1,800 pmp) and renal biopsies (99 pmp) were done. The management of
      the acute renal failure was one of the most relevant activities in the public
      renal units (13,456 cases, 230 pmp). In 2004 9,858 new cases of end-stage renal
      disease (169 pmp) were diagnosed. On December 31st 2004, 43,293 patients (741
      pmp) were on renal replacement therapy, of whom 89.7% on hemodialysis and 10.3%
      on peritoneal dialysis. Renal transplant recipients were 16,765 (287 pmp). The
      benchmark data derived from this census show interesting comparisons between
      centers, regions and groups of regions. These data realised the clinical
      management of renal disease in Italy.

PMID- 17458830
TI  - [A lie which became the truth].
AB  - We describe a 54 year-old lady, on dialysis since 6 years, with severe
      hyperparathyroidism and multinodular goiter. After total thyroidectomy and
      subtotal parathyroidectomy a Tc-99 scan revealed multiple bone lesions consistent
      with metastatic disease. In the following weeks the patient general conditions
      and bone pain markedly improved and alkaline phosphatase returned to normal
      levels. Biopsy of a bone lesion revealed that the scintigraphic pattern was a
      false positive result due to hyperparathyroidism.

PMID- 17458831
TI  - [The classics of Italian nephrology: the monograph ''Le nefropatie'' (Renal
      diseases) 1880-1946].
AB  - This paper, the first of the new feature ''The Classics of Italian Nephrology'',
      describes the monograph published in 1940 ''Le nefropatie. Manuale per i medici e
      studenti'' (Renal Diseases. Handbook for Doctors and Students). It was written by
      Adolfo Ferrata (1880-1946), who is remembered today for his important
      contributions to the advancement of hematology. The book, which has more than 400
      pages and many illustrations, especially of pathologic anatomy, is the product of
      teamwork involving several pupils and coworkers of Ferrata. It describes all
      aspects of medical renal diseases known at the time, and from an historical
      viewpoint represents an interesting testimony of the nephrological practice in
      Italy in the 1940s.

PMID- 17458832
TI  - [Focus Group: old and new needs of the neuropathic patient].

PMID- 17458833
TI  - [The "new nephrology," reality and hope: results of an analysis].

PMID- 17458834
TI  - [Stewart's quantitative approach to the acid-base balance].

PMID- 17458835
TI  - [Pro- and antitumor effects of the main immunosuppressive drugs used in the
      clinical practice of transplantation].

PMID- 17458836
TI  - A review of distress and its management in couples facing end-of-life cancer.
AB  - The aim of this review paper is to (1) provide an overview of the impact of
      cancer on the couple, (2) to identify potential outcomes for couple's
      interventions targeted specifically when one spouse is facing end of life, (3) to
      review and critique the empirical literature on psychosocial interventions for
      couple's facing end of life to date, and (4) to provide direction for research in
      this area. Based on our review, we found that there is clear evidence of
      significant distress arising from the impact of terminal illness on the marital
      relationship, which can result in greater suffering in the last months and weeks
      of life. Currently, there is a very small body of evidence on the effectiveness
      of couple interventions for those where one is in palliative care. Future
      randomized controlled trials are needed to examine the impact of couple therapy
      adapted for couples facing the end of life, and to guide in providing information
      on the number of sessions and format required for this population. Outcomes, such
      as more effective communication, reduction in the experience of hopelessness,
      uncertainty, isolation, depression, anxiety, and more adaptive coping strategies
      should be considered.

PMID- 17458837
TI  - Synthesis and characterization of monodisperse oligo(fluorene-co-bithiophene)s.
AB  - A series of monodisperse oligo(9,9-di-n-octylfluorene-co-bithiophene)s (OFbTs)
      with molecular lengths of up to 19.5 nm and molecular weights up to 7025 g mol(
      1) has been synthesized by a divergent/convergent approach involving Stille
      coupling reactions. Stille coupling is quite efficient in preparing this class of
      oligomers, and even the molecule with nine fluorene units and eight bithiophene
      units (F9Th16) can be synthesized in a yield as high as 70 %. Because of easy
      functionalization of the thiophene ring at its alpha position, no additional
      protecting group allowing activation for further reaction is necessary. However,
      the synthetic routes must be optimized to eliminate contamination of the
      targeting compounds with the homocoupling product of the organotin reagents.
      Synthesis of the longest oligomer F13Th24 in a relative large quantity is limited
      by its low yield due to the pronounced ligand-exchange side reactions of the
      starting materials and reaction intermediates. All oligomers longer than F4Th6
      are nematic mesomorphs and exhibit enhanced glass transition temperature and
      clearing point with increasing molecular length, as revealed by differential
      scanning calorimetry and polarizing optical microscopy. Absorption and
      photoluminescence (PL) measurements reveal that OFbTs are well-conjugated systems
      with an effective conjugation length longer than the length of F13Th24.

PMID- 17458838
TI  - Unexpected thermally stable, cholesteric liquid-crystalline helical
      polyisocyanides with memory of macromolecular helicity.
AB  - The achiral sodium salt of poly(4-carboxyphenyl isocyanide) (poly-1-Na) folds
      into a one-handed helix induced by optically active amines in water. The induced
      helicity remains when the optically active amines are completely removed, and
      further modification of the side groups to amide residues is possible without
      loss of memory of macromolecular helicity. Although the helical poly-1-Na loses
      its chiral memory at high temperature, helical polyisocyanides modified with
      achiral primary amines, which no longer have any chiral components, keep their
      memory perfectly even at 100 degrees C in N,N-dimethylformamide in some cases and
      exhibit cholesteric liquid-crystalline phases, thus providing a robust scaffold
      with heat resistance to which a variety of functional groups can be introduced.

PMID- 17458839
TI  - Charge decomposition analysis of the electron localizability indicator: a bridge
      between the orbital and direct space representation of the chemical bond.
AB  - The novel functional electron localizability indicator is a useful tool for
      investigating chemical bonding in molecules and solids. In contrast to the
      traditional electron localization function (ELF), the electron localizability
      indicator is shown to be exactly decomposable into partial orbital contributions
      even though it displays at the single-determinantal level of theory the same
      topology as the ELF. This approach is generally valid for molecules and crystals
      at either the single-determinantal or the explicitly correlated level of theory.
      The advantages of the new approach are illustrated for the argon atom,
      homonuclear dimers N2 and F2, unsaturated hydrocarbons C2H4 and C6H6, and the
      transition-metal-containing molecules Sc(2)2+ and TiF4.

PMID- 17458840
TI  - Desymmetrisation of a centrosymmetric molecule by carbon-carbon bond formation:
      asymmetric aldol reactions of a centrosymmetric dialdehyde.
AB  - The desymmetrisation of centrosymmetric molecules by enantioselective carbon
      carbon bond formation has been reported for the first time. A bimetallic zinc
      catalyst developed by Trost was exploited in the desymmetrisation of a
      centrosymmetric dialdehyde. The approach was successful with a range of ketone
      nucleophiles and was uniformly highly diastereoselective (>98:<2). The yield and
      the enantioselectivity of the reaction varied as a function of the ketone used,
      and the desymmetrised products were obtained in up to 74 % yield and 97 % ee
      (ee=enantiomeric excess). The desymmetrisation of centrosymmetric molecules by
      enantioselective carbon-carbon bond formation is an efficient and convergent
      synthetic approach which is likely to find wide application in synthesis,
      particularly in the total synthesis of natural products with embedded
      centrosymmetric fragments.

PMID- 17458841
TI  - Facile fabrication of hybrid colloidosomes with alginate gel cores and shells of
      porous CaCO3 microparticles.

PMID- 17458842
TI  - Synthesis and biological validation of novel synthetic histone/protein
      methyltransferase inhibitors.

PMID- 17458843
TI  - Design and synthesis of 2,3,5-substituted imidazolidin-4-one inhibitors of BACE
      1.

PMID- 17458844
TI  - DNA photography: an ultrasensitive DNA-detection method based on photographic
      techniques.

PMID- 17458845
TI  - Metal oxide "nanosponges" as chemical sensors: highly sensitive detection of
      hydrogen with nanosponge titania.

PMID- 17458847
TI  - Rewritable imaging on the surface of frozen ionic liquids.

PMID- 17458846
TI  - Photochemical activation of protein expression in bacterial cells.

PMID- 17458848
TI  - A protein-responsive chromophore based on squaraine and its application to visual
      protein detection on a Gel for SDS-PAGE.

PMID- 17458849
TI  - Integration of a self-assembling protein scaffold with water-soluble single
      walled carbon nanotubes.

PMID- 17458850
TI  - Polyamide struts for DNA architectures.

PMID- 17458851
TI  - A hexacopper fluoro metallacrown cavitand and its alkali-metal complexes.

PMID- 17458852
TI  - StereoselectiveSimmons-Smith cyclopropanation of chiral enamides.

PMID- 17458857
TI  - IL-13 induces expression of CD36 in human monocytes through PPARgamma activation.
AB  - The class B scavenger receptor CD36 is a component of the pattern recognition
      receptors on monocytes that recognizes a variety of molecules. CD36 expression in
      monocytes depends on exposure to soluble mediators. We demonstrate here that CD36
      expression is induced in human monocytes following exposure to IL-13, a Th2
      cytokine, via the peroxisome proliferator-activated receptor (PPAR)gamma pathway.
      Induction of CD36 protein was paralleled by an increase in CD36 mRNA. The
      PPARgamma pathway was demonstrated using transfection of a PPARgamma expression
      plasmid into the murine macrophage cell line RAW264.7, expressing very low levels
      of PPARgamma, and in peritoneal macrophages from PPARgamma-conditional null mice.
      We also show that CD36 induction by IL-13 via PPARgamma is dependent on
      phospholipase A2 activation and that IL-13 induces the production of endogenous
      15-deoxy-Delta12,14-prostaglandin J2, an endogenous PPARgamma ligand, and its
      nuclear localization in human monocytes. Finally, we demonstrate that CD36 and
      PPARgamma are involved in IL-13-mediated phagocytosis of Plasmodium falciparum
      parasitized erythrocytes. These results reveal a novel role for PPARgamma in the
      alternative activation of monocytes by IL-13, suggesting that endogenous
      PPARgamma ligands, produced by phospholipase A2 activation, could contribute to
      the biochemical and cellular functions of CD36.

PMID- 17458858
TI  - Syk-dependent ERK activation regulates IL-2 and IL-10 production by DC stimulated
      with zymosan.
AB  - Zymosan is a particulate yeast preparation that elicits high levels of IL-2 and
      IL-10 from dendritic cells (DC) and engages multiple innate receptors, including
      the Syk-coupled receptor dectin-1 and the MyD88-coupled receptor TLR2. Here, we
      show that induction of IL-2 and IL-10 by zymosan requires activation of ERK MAP
      kinase in murine DC. Surprisingly, ERK activation in response to zymosan is
      completely blocked in Syk-deficient DC and unaffected by MyD88 deficiency.
      Conversely, ERK activation in response to the TLR2 agonist Pam3Cys is completely
      MyD88 dependent and unaffected by Syk deficiency. The inability of TLR2 ligands
      in zymosan to couple to ERK may explain the Syk dependence of the IL-2 and IL-10
      response in DC and emphasises the importance of Syk-coupled pattern recognition
      receptors such as dectin-1 in the detection of yeasts. Furthermore, the lack of
      receptor compensation observed here suggests that responses induced by complex
      innate stimuli cannot always be predicted by the signalling pathways downstream
      of individual receptors.

PMID- 17458859
TI  - Erythropoietin enhances immune responses in mice.
AB  - Erythropoietin (Epo) is the main erythropoietic hormone. Recombinant human Epo
      (rHuEpo) is thus used in clinical practice for the treatment of anemia.
      Accumulating data reveals that Epo exerts pleiotropic activities. We have
      previously shown an anti-neoplastic activity of Epo in murine multiple myeloma
      (MM) models, and in MM patients. Our findings that this anti-neoplastic effect
      operates via CD8+ T lymphocytes led us to hypothesize that Epo possesses a wider
      range of immunomodulatory functions. Here we demonstrate the effect of Epo on B
      lymphocyte responses, focusing on three experimental models: (i) tumor-bearing
      mice, (5T2 MM mouse); (ii) antigen-injected healthy mice; and (iii) antigen
      injected transgenic mice (tg6), overexpressing human Epo. In the MM model,
      despite bone marrow dysfunction, Epo-treated mice retained higher levels of
      endogenous polyclonal immunoglobulins, compared to their untreated controls. In
      both Epo-treated wild type and tg6 mice, Epo effect was manifested in the higher
      levels of splenocyte proliferative response induced in vitro by
      lipopolysaccharide. Furthermore, these mice had increased in vivo production of
      anti-dinitrophenyl (DNP) antibodies following immunization with DNP-keyhole
      limpet hemocyanin. Epo-treated mice showed an enhanced immune response also to
      the clinically relevant hepatitis B surface antigen. These findings suggest a
      potential novel use of rHuEpo as an immunomodulator.

PMID- 17458860
TI  - Sentinel lymph node biopsy for breast cancer: indications, contraindications, and
      new directions.

PMID- 17458861
TI  - Revascularization after segmental resection of lower extremity soft tissue
      sarcomas.
AB  - BACKGROUND AND OBJECTIVES: Limb salvage surgery combined with vascular
      reconstruction has replaced amputation as the preferred treatment of soft tissue
      sarcomas involving major vascular structures of the extremities. We describe our
      experience with soft tissue sarcomas involving major vascular structures and
      examine outcomes according to the type of graft selected for arterial
      reconstruction. We also examine the effect of venous reconstruction on post
      operative edema. METHODS: This retrospective review includes 14 patients with
      lower extremity soft-tissue sarcomas that encased major vessels, requiring
      combined limb-preserving tumor resection and revascularization with a synthetic
      or autogenous saphenous vein graft. Edema in patients with and without venous
      reconstruction was compared. The incidence of infection, wound dehiscence, and
      graft thrombosis were compared according to arterial graft type. RESULTS: There
      was no significant difference in edema in patients with venous reconstruction and
      those without. There was also no significant difference in infection and graft
      thrombosis in patients with synthetic grafts and those with autogenous saphenous
      vein grafts. Wound dehiscence occurred more often in patients with synthetic
      grafts (P = 0.029). CONCLUSIONS: Although this study was small, these results
      suggest that further studies are needed to determine the roles that vascular
      graft selection and venous reconstruction play in clinical outcome.

PMID- 17458862
TI  - Assessing spiritual growth and spiritual decline following a diagnosis of cancer:
      reliability and validity of the spiritual transformation scale.
AB  - This study assessed the factor structure, reliability, and validity of an
      instrument designed to assess spiritual transformations following a diagnosis of
      cancer-the Spiritual Transformation Scale (STS). The instrument was administering
      to 253 people diagnosed with cancer within the previous 2 years. Two underlying
      factors emerged (spiritual growth (SG) and spiritual decline (SD)) with adequate
      internal reliability (alpha = 0.98 and 0.86, respectively) and test-retest
      reliability (r = 0.85 and 0.73, respectively). Validity was supported by
      correlations between SG and the Positive and Negative Affect Scale (PANAS)
      Positive Affect Subscale (r = 0.23, p < 0.001), the Daily Spiritual Experiences
      Scale (r = 0.57, p < 0.001), and the Post-traumatic Growth Inventory (r = 0.68, p
      < 0.001). SD was associated with higher scores on the Center for Epidemiological
      Studies Depression scale (r = 0.38, p < 0.001) and PANAS-Negative Affect Subscale
      (r = 0.40, p < 0.001), and lower scores on the PANAS-Positive Affect Subscale (r
      = -0.23, p < 0.001), and the Daily Spiritual Experiences Scale (r = -0.30, p <
      0.001). Hierarchical regression analyses indicated that the subscales uniquely
      predicted adjustment beyond related constructs (intrinsic religiousness,
      spiritual coping, and general post-traumatic growth). The results indicate that
      the STS is psychometrically sound, with SG predicting better, and SD predicting
      poorer, mental and spiritual well-being following a diagnosis of cancer.

PMID- 17458864
TI  - Developmental phenotypes and reduced Wnt signaling in mice deficient for pygopus
      2.
AB  - Canonical Wnt signaling involves complex intracellular events culminating in the
      stabilization of beta-catenin, which enters the nucleus and binds to LEF/TCF
      transcription factors to stimulate gene expression. Pygopus was identified as a
      genetic modifier of Wg (Wnt homolog) signaling in Drosophila, and encodes a PHD
      domain protein that associates with the beta-catenin/LEF/TCF complex. Two murine
      pygopus paralogs, mpygo1 and mpygo2, have been identified, but their roles in
      development and Wnt signaling remain elusive. In this study, we report that
      ablation of mpygo2 expression in mice causes defects in morphogenesis of both
      ectodermally and endodermally derived tissues, including brain, eyes, hair
      follicles, and lung. However, no gross abnormality was observed in embryonic
      intestine. Using a BAT-gal reporter, we found Wnt signaling at most body sites to
      be reduced in the absence of mpygo2. Taken together, our studies show for the
      first time that mpygo2 deletion affects embryonic development of some but not all
      Wnt-requiring tissues.

PMID- 17458866
TI  - A novel VEGFR3 mutation causes Milroy disease.
AB  - Milroy disease, also known as primary congenital lymphedema, is a hereditary form
      of lymphedema with autosomal dominant inheritance. Individuals with Milroy
      disease are typically characterized by congenital onset of lymphedema of the
      lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most
      cases of Milroy disease has not been established, although mutations in the
      vascular endothelial growth factor receptor VEGFR3 (FLT-4) are responsible for
      some cases with 17 mutations described to date. In this report, we describe a
      novel VEGFR3 mutation in exon 22 in a four-generation family in which congenital
      lymphedema segregates in an autosomal dominant manner. In addition to lymphedema,
      affected family members had other clinical manifestations associated with Milroy
      disease including hydrocele, ski jump toenails, large caliber veins, and
      subcutaneous thickening. We screened VEGFR3 for mutations which revealed a novel
      3059A>T transversion in exon 22 resulting in Q1020L missense mutation in the
      second tyrosine kinase domain of VEGFR3. This mutant allele segregated with
      lymphedema among affected individuals with incomplete penetrance. This is the
      first report of an exon 22 mutation in Milroy disease.

PMID- 17458867
TI  - Cyclin E/Cdk2 is required for sperm maturation, but not DNA replication, in early
      sea urchin embryos.
AB  - The cell cycle is driven by the activity of cyclin/cdk complexes. In somatic
      cells, cyclin E/cdk2 oscillates throughout the cell cycle and has been shown to
      promote S-phase entry and initiation of DNA replication. In contrast, cyclin
      E/cdk2 activity remains constant throughout the early embryonic development of
      the sea urchin and localizes to the sperm nucleus following fertilization. We now
      show that cyclin E localization to the sperm nucleus following fertilization is
      not unique to the sea urchin, but also occurs in the surf clam, and inhibition of
      cyclin E/cdk2 activity by roscovitine inhibits the morphological changes
      indicative of male pronuclear maturation in sea urchin zygotes. Finally, we show
      that inhibition of cyclin E/cdk2 activity does not block DNA replication in the
      early cleavage cycles of the sea urchin. We conclude that cyclin E/cdk2 activity
      is required for male pronuclear maturation, but not for initiation of DNA
      replication in early sea urchin development.

PMID- 17458869
TI  - Vestiges of vibrissal capsular muscles exist in the human upper lip.
AB  - In nonhuman mammals, sinus hairs grow around the nostrils and serve for tactile
      sensation. The hair follicles of sinus hairs are rooted in vibrissal capsular
      muscles connected to the underlying, deeper orbicularis oris, thereby enabling
      the voluntary movement of sinus hairs. These vibrissal capsular muscles as well
      as the sinus hairs are believed to have been lost during human evolution, and no
      previous reports can be found on the existence of vestiges of sinus hairs in
      humans. Our study, however, has now verified the existence of vestigial muscles
      of vibrissae in the human upper lip. Using conventional histological techniques,
      microscopic observations were made on specimens obtained from the upper lips of
      human adult cadavers. In 35% of these individuals, several striated muscle
      fascicles diverging from the underlying orbicularis oris and reaching the hair
      follicles were observed. Histological findings of the vibrissal capsular muscle
      complex suggest that these fascicles are a vestigial remnant of the sinus hair
      muscle.

PMID- 17458870
TI  - Re: Anatomical examination of the recurrent artery of Heubner.

PMID- 17458871
TI  - Mutational analysis of 105 mucopolysaccharidosis type VI patients.
AB  - Mucopolysaccharidosis type VI (MPS VI; Maroteaux-Lamy syndrome) is a lysosomal
      storage disorder caused by mutations in the N-acetylgalactosamine-4-sulfatase
      (arylsulfatase B, ARSB) gene. ARSB is a lysosomal enzyme involved in the
      degradation of the glycosaminoglycans (GAG) dermatan and chondroitin sulfate.
      ARSB mutations reduce enzyme function and GAG degradation, causing lysosomal
      storage and urinary excretion of these partially degraded substrates. Disease
      onset and rate of progression is variable, producing a spectrum of clinical
      presentation. In this study, 105 MPS VI patients-representing about 10% of the
      world MPS VI population-were studied for molecular genetic and biochemical
      parameters. Direct sequencing of patient genomic DNA was used to identify ARSB
      mutations. In total, 83 different disease-causing mutations were found, 62 of
      which were previously unknown. The novel sequence changes included: 38 missense
      mutations, five nonsense mutations, 11 deletions, one insertion, seven splice
      site mutations, and four polymorphisms. ARSB mutant protein and residual activity
      were determined on fibroblast extracts for each patient. The identification of
      many novel mutations unique to individuals/their families highlighted the genetic
      heterogeneity of the disorder and provided an appropriate cohort to study the MPS
      VI phenotypic spectrum. This mutation analysis has identified a clear correlation
      between genotype and urinary GAG that can be used to predict clinical outcome.

PMID- 17458872
TI  - Clinical, biochemical, and mutational spectrum of peroxisomal acyl-coenzyme A
      oxidase deficiency.
AB  - Peroxisomal acyl-coenzyme A (acyl-CoA) oxidase deficiency is an autosomal
      recessive inborn error of peroxisomal fatty acid oxidation due to a deficiency of
      straight-chain acyl-CoA oxidase (SCOX). The biochemical hallmark of this disorder
      is the accumulation of very long-chain fatty acids. Although some case reports
      and small series of patients have been published, a comprehensive overview of the
      clinical, biochemical, and mutational spectrum of this disorder is still lacking.
      For this reason, we report clinical information for a cohort of 22 patients with
      peroxisomal acyl-CoA oxidase deficiency and the results from biochemical and
      mutation analyses in fibroblasts of the patients. No clear genotype-phenotype
      correlation was observed. An intriguing mutation in the alternatively-spliced
      transcript encoding the isoform SCOX-exon 3II in a patient with normal expression
      of the transcript encoding the isoform SCOX-exon 3I, prompted us to characterize
      these two isoforms of human SCOX. The recombinant SCOX-exon 3I displayed activity
      toward medium-chain fatty acyl-CoAs and was not active with very long-chain fatty
      acyl-CoAs. In contrast, recombinant SCOX-exon 3II was capable of oxidizing a
      broad range of substrates, including very long-chain fatty acyl-CoAs. These
      results explain why this patient with a mutation in exon 3II of the ACOX1 gene,
      but with normal expression of exon 3I, was indistinguishable from other patients
      with peroxisomal acyl-CoA oxidase deficiency with respect to his clinical
      presentation and the biochemical abnormalities in his fibroblasts.

PMID- 17458873
TI  - Cognitive outcome in pediatric brain tumor survivors: delayed attention deficit
      at long-term follow-up.
AB  - BACKGROUND: Treatment of childhood brain tumors has often been associated with
      long-term cognitive morbidity in children. Our previous research identified age
      at diagnosis, polytherapy and brain radiation dose as treatment factors affecting
      neuropsychological outcome most strongly in children with cancer 1. Our current
      goal was to measure the change across different cognitive functions. PROCEDURE:
      This study examined the cognitive outcome over repeat testing in a heterogeneous
      sample of 18 children with brain tumors. Tumor types included medulloblastoma and
      glioma. ANOVA's for repeated measures were used to evaluate the changes in
      cognitive domains across follow-up evaluations. RESULTS: Consistent with previous
      findings, the most deleterious effects were seen on IQ indices of non verbal
      cognitive ability, visual perceptual skills and information processing speed.
      Analyses reveal that the attentional factor, Freedom from Distractibility, is the
      only IQ index that declines over subsequent testing. The statistical decline was
      attributable to a significant decline on the arithmetic subtest, as well as a non
      significant trend for the auditory attention span subtest. CONCLUSIONS: This
      study reveals that while most indices remained stable over repeat testing,
      auditory attention and concentration skills decline. Long-term outcome is
      discussed in light of the high prevalence of attention and mathematic
      difficulties reported in these children and the need for preventive and remedial
      approaches.

PMID- 17458874
TI  - Treatment of neurodegenerative CNS disease in Langerhans cell histiocytosis with
      a combination of intravenous immunoglobulin and chemotherapy.
AB  - BACKGROUND: In rare cases, patients with Langerhans cell histiocytosis (LCH)
      develop neurodegenerative CNS disease (ND-CNS-LCH). Management of ND-CNS-LCH has
      not been established. METHODS: We treated five pediatric patients with a
      combination of intravenous immunoglobulin (IVIG) and chemotherapy (steroid +/-
      vinblastine +/- 6-mercaptopurine +/- methotrexate). Prior to the therapy, three
      of the five patients had cerebellar ataxia while the remaining two had abnormal
      MRI findings without apparent neurological deficits. IVIG was given monthly or
      twice monthly at the dosage of 250-400 mg/kg/dose. RESULTS: The four patients
      administered more than 23 doses of IVIG and chemotherapy remained in a stable
      condition and did not show significant progression signs in neurological deficits
      or brain MRI findings during the 30-month follow-up period (median; range: 19+ to
      38+) following the initiation of therapy for ND-CNS-LCH. CONCLUSION: The IVIG
      containing treatment may be promising for ND-CNS-LCH; however, its effectiveness
      remains to be further tested in more patients as well as in a randomized trial.

PMID- 17458875
TI  - Pneumocystis pneumonia in children receiving chemotherapy.
AB  - Pneumocystis pneumonia (PCP) is a serious complication of chemotherapy-induced
      immunosuppression. Trimethoprim-sulfamethoxazole (TMP-SMZ) given twice daily, 3
      days every week is considered the best form of prophylaxis for PCP. We evaluated
      PCP prophylaxis in all children up to 18 years of age undergoing cancer
      chemotherapy over a 2-year period. Four children were diagnosed with PCP over 24
      months. Two of 12 children on intravenous pentamidine, 1 of 143 on TMP-SMZ and 1
      of 36 on dapsone for PCP prophylaxis developed PCP. Intravenous pentamidine may
      not be as effective as previously considered and should be used with caution.

PMID- 17458876
TI  - How far should we go with cost-utility analysis when treating children with acute
      idiopathic thrombocytopenic purpura?

PMID- 17458877
TI  - Renal failure does not preclude cure in children receiving chemotherapy for Wilms
      tumor: a report from the National Wilms Tumor Study Group.
AB  - BACKGROUND: Children with Wilms tumor can develop renal failure during treatment.
      Since there are few published data concerning the appropriate chemotherapy for
      this situation, we reviewed the experience of children who developed renal
      failure while being treated on National Wilms Tumor Study Group (NWTSG) studies 1
      4 (1969-1994). PATIENTS AND METHODS: Data files in the NWTSG Data Center for all
      patients with Wilms tumor were screened. Patient demographics and tumor and
      treatment data were abstracted from those who developed renal failure. RESULTS:
      Twenty-eight of 5,910 (0.47%) children with Wilms tumor registered on NWTSG
      studies I through IV (1971-1994) were treated with chemotherapy after developing
      renal failure. Among these patients vincristine at full dose (0.05 mg/kg dose)
      did not increase the risk of severe toxicity. Dactinomycin (full dose: 15 mcg/kg
      day x 5) increased the risk for severe neutropenia when given at 75-100% of full
      dose. There was no compelling evidence for increased toxicity of doxorubicin when
      given at 100% versus 50% dosing (full dose: 20 mg/m(2) day x 3), but the number
      of patients analyzed was small. The overall survival percentage was 39%, but 64%
      for those patients who were in their initial treatment phase at the time of renal
      failure. CONCLUSION: The data suggest that, in the setting of renal failure,
      reduction of dosing is not necessary for the three main agents used for treatment
      of newly diagnosed Wilms tumor, and cure is not precluded. Accurate pharmacologic
      and pharmacokinetic studies are needed for any patient being treated while in
      renal failure.

PMID- 17458878
TI  - Novel Plexor SNP genotyping technology: comparisons with TaqMan and homogenous
      MassEXTEND MALDI-TOF mass spectrometry.
AB  - Analysis of SNPs for association, linkage, haplotype, and pharmacogenetic studies
      has led to a dramatic increase in the number and evolution of medium- to high
      throughput genotyping technologies. This study introduces Plexor as a new method
      for medium-throughput (single SNP) genotyping. We compare this fluorescent-based
      chemistry for call rate, accuracy, affordability, throughput, and overall
      efficiency against two commonly used technologies. These include fluorescent
      based TaqMan allelic discrimination for single SNP analysis (medium-throughput)
      and the homogenous MassEXTEND (hME) chemistry using matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for multiple
      SNP analysis (high-throughput). Analysis of 11 SNPs, including all six possible
      nucleotide substitutions, showed Plexor to be highly comparable for both call
      rate (94.7%) and accuracy (99.2%) to the TaqMan (94.6% and 99.8%, respectively)
      and hME (91.9% and 98.1%, respectively) chemistries. We demonstrate that this
      novel method is an efficient, cost-effective alternative to TaqMan genotyping
      commonly used in diagnostic settings.

PMID- 17458879
TI  - Flow cytometric measurement of calpain activity in living cells.
AB  - BACKGROUND: Calpains are intracellular, calcium-sensitive, neutral cysteine
      proteases that play crucial roles in many physiological and pathological
      processes. Calpain regulation is complex and activity is poorly correlated with
      calpain protein levels. Therefore a full understanding of calpain function
      requires robust methods for measuring activity. METHODS: We describe and
      characterize a flow cytometric method for measuring calpain activity in live
      cells. This method uses the BOC-LM-CMAC reagent that readily diffuses into cells
      where it reacts with free thiols to enhance retention. RESULTS: We show that the
      reagent is cleaved specifically by calpains and follows saturation kinetics. We
      use the assay to measure calpain activation following PDGF stimulation of rat
      fibroblasts. We also show that the calpain inhibitor PD150606 inhibits calpain
      with a K(i) of 12.5 muM and show that Mek inhibitors PD89059 and U0126 also
      suppress calpain activity. We also show that the assay can measure calpain
      activity in subpopulations of cells present in unfractionated cord blood or in
      HL60 human myelomonocytic leukemia cells. CONCLUSION: Taken together, these
      experiments demonstrate that this assay is a reliable and useful method for
      measuring calpain activity in multiple cell types.

PMID- 17458880
TI  - Monocyte cholesterol homeostasis correlates with the presence of detergent
      resistant membrane microdomains.
AB  - BACKGROUND: Lipid membrane microdomains are involved in the regulation of
      biological functions of monocyte membrane proteins. These microdomains show a
      relative resistance to non-ionic detergents providing an easy analytical tool to
      study them. METHODS: Here, we applied a rapid detergent-based flow cytometric
      assay to investigate microdomain association of proteins on monocytes from whole
      blood samples. The association of known surface antigens with detergent resistant
      fraction of membranes (DRMs) was compared using monocytes from healthy blood
      donors, patients with genetic disorders affecting cellular cholesterol traffic
      and patients with systemic inflammatory response. RESULTS: All investigated
      surface antigens of Niemann-Pick type C (NPC)-mutant monocytes with impaired
      cholesterol influx and defective late endosome cholesterol trafficking, presented
      a strongly increased DRM-association. Though, membrane antigens of ATP binding
      cassette transporter A1 (ABCA1)-mutant monocytes with impaired cholesterol efflux
      did not show alterations in DRM-association. Differential CD14-dependent receptor
      clustering within microdomains was also investigated in response to in vivo
      lipopolysaccharide (LPS) and/or atherogenic lipoprotein activation. Increased DRM
      association of the GPI-anchored proteins CD14, CD55, the Fcgamma receptor CD64,
      the scavenger receptors CD36, CD91 and CD163, the integrin CD11a, and complement
      receptor 3 complex CD11b/CD18 were observed from patients with systemic
      inflammatory response syndrome (SIRS)/sepsis or coronary artery disease
      (CAD)/myocardial infarction. Interestingly, the tetraspanin CD81 presented
      increased DRM-association in SIRS/sepsis patients, but not in CAD patients.
      Moreover, the pentaspanin CD47 and the Fcgamma RIII CD16 showed an increased DRM
      partition in CAD patients but disassembled from DRMs in SIRS/sepsis patients.
      CONCLUSIONS: Our results demonstrate that flow cytometric analysis of short time
      in situ detergent extraction provides a powerful tool for rapid screening of
      blood monocyte DRMs to preselect patients with potential raft/microdomain
      abnormalities for more detailed analysis.

PMID- 17458881
TI  - Monitoring dynamic protein expression in living E. coli. Bacterial cells by laser
      tweezers Raman spectroscopy.
AB  - BACKGROUND: Laser tweezers Raman spectroscopy (LTRS) is a novel, nondestructive,
      and label-free method that can be used to quantitatively measure changes in
      cellular activity in single living cells. Here, we demonstrate its use to monitor
      changes in a population of E. coli cells that occur during overexpression of a
      protein, the extracellular domain of myelin oligodendrocyte glycoprotein [MOG(1
      120)]. METHODS: Raman spectra were acquired from individual E. coli cells
      suspended in solution and trapped by a single tightly focused laser beam.
      Overexpression of MOG(1-120) in transformed E. coli Rosetta-Gami (DE3)pLysS cells
      was induced by addition of isopropyl thiogalactoside (IPTG). Changes in the peak
      intensities of the Raman spectra from a population of cells were monitored and
      analyzed over a total duration of 3 h. Data were also collected for concentrated
      purified MOG(1-120) protein in solution, and the spectra compared with that
      obtained for the MOG(1-120) expressing cells. RESULTS: Raman spectra of
      individual, living E. coli cells exhibit signatures due to DNA and protein
      molecular vibrations. Characteristic Raman markers associated with protein
      vibrations, such as 1,257, 1,340, 1,453, and 1,660 cm(-1), are shown to increase
      as a function of time following the addition of IPTG. Comparison of these spectra
      and the spectra of purified MOG protein indicates that the changes are
      predominantly due to the induction of MOG protein expression. Protein expression
      was found to occur mostly within the second hour, with a 470% increase relative
      to the protein expressed in the first hour. A 230% relative increase between the
      second and third hour indicates that protein expression begins to level off
      within the third hour. CONCLUSION: It is demonstrated that LTRS has sufficient
      sensitivity for real-time, nondestructive, and quantitative monitoring of
      biological processes, such as protein expression, in single living cells. Such
      capabilities, which are not currently available in flow cytometry, open up new
      possibilities for analyzing cellular processes occurring in single microbial and
      eukaryotic cells.

PMID- 17458882
TI  - Optimized amplification and fluorescent labeling of small cell samples for
      genomic array-CGH.
AB  - BACKGROUND: Whole genome amplification (WGA) is usually needed in the genetic
      analysis of samples containing a low number of cells. In genome-wide analysis of
      DNA copy numbers by array comparative genomic hybridization (array-CGH) it is
      very important that the genome is evenly represented throughout the amplified
      product. All currently available WGA techniques are generating some degree of
      bias. METHODS: A way to compensate for this is using a reference sample which is
      similarly amplified, as the introduced amplification bias will be leveled out.
      Additionally, direct labeling of the amplified DNA is performed to bypass the
      currently widely applied random primed labeling, which involves an additional
      amplification of the product and is introducing extra bias. RESULTS: In this
      article it is shown that equal processing of the test and reference sample is
      indeed crucial to generate an optimal array-CGH profile of amplified DNA samples.
      Also presented here is that the labeling method may significantly effect the
      array-CGH result, it is shown that with direct chemical labeling using platinum
      derivates (ULS labeling) optimal array-CGH results are obtained. CONCLUSIONS: We
      show that an optimized WGA strategy for both test and reference sample in
      combination with direct chemical labeling results in a reliable array-CGH profile
      of samples as low as a 30 cell equivalent.

PMID- 17458883
TI  - CD4dimCD25bright Treg cell frequencies above a standardized gating threshold are
      similar in asthmatics and controls.
AB  - BACKGROUND: Thymus selected CD4(+)CD25(bright) natural regulatory Treg cells
      expressing FOXP3 may contribute to control of immune responses. No unique markers
      have been available to identify and characterize Treg. We present a gating
      strategy that allows enumeration of Treg on the basis of CD4 and CD25 and
      investigate whether asthmatics have fewer Treg than controls. METHODS: Asthmatics
      and controls were selected from responses to a mailed questionnaire. CD25, CD4,
      HLA DR, and appropriate isotypes were recorded by flow cytometry. RESULTS: The
      CD4 T cells expressing most CD25 are a separate population expressing FOXP3 and
      lower levels of CD4 and CD127. On a CD4 CD25 dot-plot, the CD4 MFI of Treg for
      152 participants was calculated to be 0.83 +/- 0.043*MFI of CD25(bright) T-cells.
      CD4(dim)CD25(bright) T cells in a rectangular gate with a CD4 MFI </= 0.9 (0.83 +
      [2*0.043])*MFI of CD25(+) T cells were enumerated and shown to be similar for
      controls (median 8.34%) and asthmatics (median 10.1%). HLA DR expression on Treg
      correlated with CD25 expression. CONCLUSIONS: A standardized two color gating
      method defines Treg. It may be applied in most clinical scenarios and is useful
      for sorting viable Treg. Asthmatics and controls have similar numbers of Treg.

PMID- 17458884
TI  - Effects of caspase inhibitors (z-VAD-fmk, z-VDVAD-fmk) on Nile Red fluorescence
      pattern in 7-ketocholesterol-treated cells: investigation by flow cytometry and
      spectral imaging microscopy.
AB  - BACKGROUND: The 7-ketocholesterol (7KC)-induced cell death has some
      characteristics of apoptosis and is associated with polar lipid accumulation. So,
      we investigated the effects of the broad-spectrum caspase inhibitor z-VAD-fmk and
      of the caspase-2 inhibitor z-VDVAD-fmk on lipid profile evaluated by staining
      with Nile Red (NR). METHODS: The 7KC-treated human monocytic U937 cells were
      cultured in the absence or in the presence of the caspase inhibitors z-VAD-fmk or
      z-VDVAD-fmk. When staining with NR is performed, neutral and polar lipids have
      yellow and orange/red emission, respectively, and fluorescence was then analyzed
      by flow cytometry (FCM) and by confocal laser scanning microscopy (CLSM) combined
      with subsequent image processing. The 3D-image sequences were obtained by means
      of CLSM using spectral analysis, and were analyzed by the factor analysis of
      medical image sequences algorithm to differentiate spectra inside mixed
      fluorescence emission and get corresponding specific images. RESULTS: By FCM,
      comparatively to untreated cells, higher percentages of red fluorescent cells
      were identified in 7KC-treated cells. Factor curves and images reveal orange and
      red fluorescence emissions in 7KC-treated cells and show yellow, orange, and red
      fluorescence emissions in 7KC-treated cells cultured in the presence of z-VAD-fmk
      or z-VDVAD-fmk. CONCLUSIONS: Our data support that investigation by FCM and by
      spectral analysis in CLSM associated with subsequent image processing provides
      useful tools to determine the effect of caspase inhibitors on lipid content
      evaluated with NR. They also favor the hypothesis of relationships between
      caspase activity and polar lipid accumulation.

PMID- 17458885
TI  - Efficient selection of silenced primary cells by flow cytometry.
AB  - BACKGROUND: RNA interference has emerged as a new and potent tool to knockdown
      the expression of target genes and to investigate their functions. For short time
      experiments with mammalian cell lines, RNA interference is typically induced by
      transfecting small interfering RNAs (siRNAs). Primary cells constitute important
      experimental systems in many studies because of their similarity to their in vivo
      counterparts; however, transfection of these cells has been found to be
      difficult. As a consequence, RNA interference of primary cells may result in
      mixed phenotypes because of the simultaneous presence in the same preparation of
      transfected and nontransfected cells. This may be particularly inconvenient when
      certain experiments (for example, biochemical analysis) should be performed.
      METHODS: We use fluorescently labeled siRNAs to induce RNA interference in
      fibroblasts, and flow-cytometry associated cell sorting to separate
      subpopulations of transfected cells according to fluorescence intensity. RESULTS:
      Flow cytometry allows one to discriminate between strongly- and weakly- or
      nonsilenced fibroblasts, since the fluorescence intensity of transfected cells is
      related to the number of internalized siRNA copies and to the mRNA knockdown
      efficiency. CONCLUSIONS: The use of fluorescently labeled siRNAs may allow one to
      isolate by flow-cytometry associated cell sorting the most efficiently silenced
      primary cells for subsequent analysis.

PMID- 17458886
TI  - Morphology of the femoral glands in the lizard Ameiva ameiva (teiidae) and their
      possible role in semiochemical dispersion.
AB  - Many lizards have epidermal glands in the cloacal or femoral region with
      semiochemical function related to sexual behavior and/or territorial demarcation.
      Externally, these glands are recognized as a row of pores, opening individually
      in the center of a modified scale. In many species the pores are used as
      systematic characters. They form a glandular cord or, in some species, a row of
      glandular beads below the dermis, and are connected to the exterior through the
      ducts, which continuously liberate a solid secretion. Dead cells, desquamated
      from the secretory epithelium, constitute the secretion, known as "a secretion
      plug." The present work focuses on the morphology of the femoral glands of the
      teiid lizard Ameiva ameiva, correlating it to the way in which the secretion is
      deposited in the environment. The results here obtained are compared to those
      available for other lizards and amphisbaenians. We observed that the diameter of
      the glandular pores did not show significant differences between males and
      females. The glands comprise germinative and secretory cells, which pass through
      at least three stages of differentiation, during which an accumulation of
      cytoplasmic granules, with a glycoprotein content, occurs. The cells eventually
      die and desquamate from the secretory epithelium, forming a secretory plug mostly
      constituted by juxtaposed nonfragmented secretory cells. Because of the
      arrangement of the rosette-like scales surrounding the femoral pores, we suggest
      that when the animal is in a resting position, with its femoral regions touching
      the ground, these scales may be involved in the breakage of their respective
      plugs, depositing tiny portions on the substrate. In this manner, it seems that
      the method for signal dispersion in this species involves specifically adapted
      structures and does not simply involve the chance breakage of the plug, as the
      gland secretes it. Signal dispersion must also be intimately associated with the
      animal's movement within its territory.

PMID- 17458887
TI  - Fundamentals of viviparity: comparison of seasonal changes in the uterine
      epithelium of oviparous and viviparous Lerista bougainvillii (Squamata:
      Scincidae).
AB  - Distinct differences in epithelial response between oviparous and viviparous
      species of skinks led us to investigate morphological differences in the uterus
      of a species that exhibits bi-modal reproduction and that may indicate
      specialities for the different requirements of viviparity and oviparity. The
      uteri of females from oviparous and viviparous populations of the Australian
      scincid lizard, Lerista bougainvillii, are described in detail to determine
      whether the occurrence of uterodomes and the plasma membrane transformation,
      found in other viviparous species but not oviparous species, are indeed features
      characteristic of viviparity. Oviductal tissue was dissected at three different
      stages of reproduction from lizards from both populations: 1) vitellogenic, 2)
      gravid or pregnant, and 3) non-reproductive or quiescent. Tissue was observed
      using both scanning and transmission electron microscopy. Lerista bougainvillii
      has a simple placental morphology with simple squamous epithelium. In contrast to
      mammals and other viviparous skinks, L. bougainvillii does not undergo a plasma
      membrane transformation, but early signs of placentation in viviparous
      individuals are indicated by changes in the uterine surface that occur largely
      after embryonic stage 30. There are no obvious cellular differences between the
      uteri of oviparous and viviparous L. bougainvillii at the non-reproductive and
      vitellogenic phase of the reproductive cycle but throughout gestation/gravidity,
      the cellular differences that could be related to the changing functional
      requirements with the retention of the viviparous embryo, became apparent. A
      plasma membrane transformation with ensuing uterodome formation does not occur,
      which suggests that these more sophisticated changes are a feature of advanced
      placental development in reptiles.

PMID- 17458888
TI  - Morphology and mechanics of the teeth and jaws of white-spotted bamboo sharks
      (Chiloscyllium plagiosum).
AB  - The teeth of white-spotted bamboo sharks (Chiloscyllium plagiosum) are used to
      clutch soft-bodied prey and crush hard prey; however, the dual function is not
      evident from tooth morphology alone. Teeth exhibit characteristics that are in
      agreement with a clutching-type tooth morphology that is well suited for grasping
      and holding soft-bodied prey, but not for crushing hard prey. The dual role of
      this single tooth morphology is facilitated by features of the dental ligament
      and jaw joint. Tooth attachment is flexible and elastic, allowing movement in
      both sagittal and frontal planes. During prey capture spike-like tooth cusps
      pierce the flesh of soft prey, thereby preventing escape. When processing prey
      harder than the teeth can pierce the teeth passively depress, rotating inward
      towards the oral cavity such that the broader labial faces of the teeth are
      nearly parallel to the surface of the jaws and form a crushing surface. Movement
      into the depressed position increases the tooth surface area contacting prey and
      decreases the total stress applied to the tooth, thereby decreasing the risk of
      structural failure. This action is aided by a jaw joint that is ventrally offset
      from the occlusal planes of the jaws. The offset joint position allows many teeth
      to contact prey simultaneously and orients force vectors at contact points
      between the jaws and prey in a manner that shears or rolls prey between the jaws
      during a bite, thus, aiding in processing while reducing forward slip of hard
      prey from the mouth. Together the teeth, dental ligament, and jaws form an
      integrated system that may be beneficial to the feeding ecology of C. plagiosum,
      allowing for a diet that includes prey of varying hardness and elusiveness.

PMID- 17458889
TI  - C(6)-ceramide inhibited Na(+) currents by intracellular Ca(2+) release in rat
      myoblasts.
AB  - Ceramides are novel second messengers that may mediate signaling leading to
      apoptosis and the regulation of cell cycle progression. Moreover, ceramide
      analogs have been reported to directly modulate K(+) and Ca(2+) channels in
      different cell types. In this report, the effect of C(6)-ceramide on the voltage
      gated inward Na(+) currents (I(Na)) in cultured rat myoblasts was investigated
      using whole-cell current recording and a fluorescent Ca(2+) imaging experiment.
      At concentrations of 1-100 microM, ceramide produced a dose-independent and
      reversible inhibition of I(Na). Ceramide also significantly shifted the steady
      state inactivation curve of I(Na) by 16 mV toward the hyperpolarizing potential,
      but did not alter the steady-state activation properties. C(2)-ceramide caused a
      similar inhibitory effect on I(Na) amplitude. However, dihydro-C(6)-ceramide, the
      inactive analog of ceramide, failed to modulate I(Na). The effect of C(6)
      ceramide on I(Na) was abolished by intracellular infusion of the Ca(2+)-chelating
      agent BAPTA, but was mimicked by application of caffeine. Blocking the release of
      Ca(2+) from the sarcoplasmic reticulum with xestospongin C or heparin, an
      inositol 1,4,5-trisphosphate (IP(3)) receptor blocker, induced a gradual increase
      in I(Na) amplitude and eliminated the effect of ceramide on I(Na). In contrast,
      ruthenium red, which is a blocker of the ryanodine-sensitive Ca(2+) receptor did
      not affect the action of C(6)-ceramide on I(Na). Intracellular application of the
      G-protein agonist GTPgammaS also induced a gradual decrease in I(Na) amplitude,
      while the G-protein antagonist GDPbetaS eliminated the effect of C(6)-ceramide on
      I(Na). Calcium imaging showed that C(6)-ceramide could give rise to a significant
      elevation of intracellular calcium. Our data show that increased calcium release
      through the IP(3)-sensitive Ca(2+) receptor, which probably occurred through the
      G-protein and phospholipase C pathway, may be responsible for C(6)-ceramide
      induced inhibition of the I(Na) of rat myoblasts.

PMID- 17458890
TI  - AKT and MAPK signaling in KGF-treated and UVB-exposed human epidermal cells.
AB  - Regulation of proliferation and differentiation in keratinocyte is a complex and
      dynamic process that involves activation of multiple signaling pathways triggered
      by different growth factors. Keratinocyte growth factor (KGF) is not only a
      potent mitogen, but differently from other growth factors, is a potent inducer of
      differentiation. The MAP kinase and AKT pathways are involved in proliferation
      and differentiation of many cell types including keratinocytes. We investigated
      here the role of KGF in modulating AKT and MAPK activity during differentiation
      of human keratinocytes. Our results show that the mechanisms of action of KGF are
      dose-dependent and that a sustained activation of the MAPK signaling cascade
      causes a negative regulation of AKT. We also demostrated increasing expression of
      KGFR substrates, such as PAK4 during keratinocyte differentiation parallel to the
      receptor upregulation.

PMID- 17458891
TI  - WWOX in biological control and tumorigenesis.
AB  - The WW domain-containing oxidoreductase (WWOX) gene is located at 16q23.1
      16q23.2, a region that spans the second most common human fragile site, FRA16D.
      The WWOX protein contains two N-terminal WW domains and a central short chain
      oxidoreductase-like domain. In the last few years, considerable amount of data
      have shown inactivation of WWOX in a variety of human malignancies. Moreover,
      interacting partners have been identified biochemically that define, at least in
      part, the molecular mechanism of WWOX action. Recently, we demonstrated that
      targeted deletion of the Wwox gene in the mouse led to increased incidence of
      spontaneous and chemically induced tumor formation, thereby providing the first
      in vivo evidence that WWOX is a bona fide tumor suppressor. This review focuses
      on the most recent progress in understanding WWOX function as a tumor suppressor.

PMID- 17458892
TI  - The immunomodulatory protein SV-IV protects serum-deprived cells against
      apoptosis but not against G0/G1 arrest: possible implications for the survival of
      implanting embryo.
AB  - Serum deprivation induced in human lymphoblastoid Raji cells oxidative stress
      associated apoptotic death and G0/G1 cell cycle arrest. Addition into culture
      medium of the immunomodulatory protein Seminal vesicle protein 4 (SV-IV)
      protected these cells against apoptosis but not against cycle arrest. The
      antiapoptotic activity was related to: (1) decrease of endocellular reactive
      Oxygen species (ROS) (2) increase of mRNAs encoding anti-oxidant enzymes
      (catalase, G6PD) and antiapoptotic proteins (survivin, cox-1, Hsp70, c-Fos); (3)
      decrease of mRNAs encoding proapoptotic proteins (c-myc, Bax, caspase-3, Apaf-1).
      The biochemical changes underlaying these effects were probably induced by a
      protein tyrosine kinase (PTK) activity triggered by the binding of SV-IV to its
      putative plasma membrane receptors. The ineffectiveness of SV-IV to abrogate the
      cycle arrest was accounted for by its downregulating effects on D1,3/E G1-cyclins
      and CdK2/4 gene expression, ppRb/pRb ratio, and intracellular ROS concentration.
      In conclusion, these experiments: (1) prove that SV-IV acts as a cell survival
      factor; (2) suggest the involvement of a PTK in SV-IV signaling; (3) point to
      cell cycle-linked enzyme inhibition as responsible for cycle arrest; (4) provide
      a model to dissect the cycle arrest and apoptosis induced by serum withdrawal;
      (5) imply a possible role of SV-IV in the survival of hemiallogenic implanting
      embryos.

PMID- 17458893
TI  - Epigenetic drugs as pleiotropic agents in cancer treatment: biomolecular aspects
      and clinical applications.
AB  - In the last three decades huge efforts have been made to characterize genetic
      defects responsible for cancer development and progression, leading to the
      comprehensive identification of distinct cellular pathways affected by the
      alteration of specific genes. Despite the undoubtable role of genetic mechanisms
      in triggering neoplastic cell transformation, epigenetic modifications (i.e.,
      heritable changes of gene expression that do not derive from alterations of the
      nucleotide sequence of DNA) are rapidly emerging as frequent alterations that
      often occur in the early phases of tumorigenesis and that play an important role
      in tumor development and progression. Epigenetic alterations, such as
      modifications in DNA methylation patterns and post-translational modifications of
      histone tails, behave extremely different from genetic modifications, being
      readily revertable by "epigenetic drugs" such as inhibitors of DNA methyl
      transferases and inhibitors of histone deacetylases. Since epigenetic alterations
      in cancer cells affect virtually all cellular pathways that have been associated
      to tumorigenesis, it is not surprising that epigenetic drugs display pleiotropic
      activities, being able to concomitantly restore the defective expression of genes
      involved in cell cycle control, apoptosis, cell signaling, tumor cell invasion
      and metastasis, angiogenesis and immune recognition. Prompted by this emerging
      clinical relevance of epigenetic drugs, this review will focus on the large
      amount of available data, deriving both from in vitro experimentations and in
      vivo pre-clinical and clinical studies, which clearly indicate epigenetic drugs
      as effective modifiers of cancer phenotype and as positive regulators of tumor
      cell biology with a relevant therapeutic potential in cancer patients.

PMID- 17458894
TI  - Iressa strengthens the cytotoxic effect of docetaxel in NSCLC models that harbor
      specific molecular characteristics.
AB  - Non-small cell lung cancer (NSCLC) is the most lethal malignant tumor and is also
      considered one of the most chemoresistant cancers. Despite the benefits obtained
      from platinum-based therapy, the majority of patients treated will progress and
      die. In the continuing quest for personalized therapy based on the biomolecular
      characteristics of each single patient, clinical practice now seems to be
      oriented towards combining conventional drugs with molecular-targeted agents. In
      the present study, we evaluated the antitumor activity of docetaxel, one of the
      most widely used drugs for second-line treatment, and Iressa, an EGFR-targeting
      tyrosine kinase inhibitor, administered singly or in sequence. The study was
      performed on three human NSCLC cell lines (ChaGo-K1, CAEP and RAL) that exhibit
      different expression of proliferation and apoptosis-related markers, and do not
      harbor EGFR mutations. The efficacy of docetaxel and Iressa differed in the three
      cell lines and an important synergistic interaction was observed with the
      sequence 1-h docetaxel --> 72-h Iressa during which Iressa doubled the fraction
      of docetaxel-induced apoptotic cells, amplifying a caspase-dependent apoptosis
      and inhibiting docetaxel-induced p21 hyperexpression. Moreover, the important
      role of MAPK-dependent modulation of this molecular marker was shown using a
      specific inhibitor. The results from the present preclinical study demonstrate
      the cytotoxic activity of Iressa and its ability to increase taxane activity in a
      model that does not harbor EGFR-specific mutations, thus highlighting the
      importance of focusing on alternative molecular targets of Iressa activity.

PMID- 17458895
TI  - Estrogen receptor alpha (ERalpha) and insulin-like growth factor I receptor (IGF
      IR) cross-talk in the gonadotropic alphaT3-1 cell line.
AB  - In reproductive tissues such as the breast and the uterus, cell proliferation and
      differentiation is strongly regulated by complex interactions between estrogen
      receptor alpha (ERalpha) and growth factor receptors. In the present study, we
      investigated the potential occurrence of such cross-talk in the murine,
      gonadotropic alphaT3-1 cell line, which expresses ERalpha and the IGF-I receptor
      (IGF-IR). Under estrogen-free conditions, basal cell proliferation and ER
      mediated gene transcription was strongly inhibited by the selective estrogen
      receptor modulator (SERM) 4-hydroxy-tamoxifen (4-OH-Tam) and by the pure anti
      estrogen ICI 182,780 (ICI). These effects can be reversed by either 17-beta
      estradiol (E(2)) or insulin-like growth factor I (IGF-I), both exerting modest
      mitogenic effects in the alphaT3-1 cell line. Furthermore, IGF-I enhanced both
      basal and E(2)-induced ER-driven gene transcription. This may be explained, at
      least in part, by enhanced phosphorylation of ERalpha at serine 118, a
      prerequisite for the transactivation capacity of the receptor. Finally, the IGF-I
      induced response on cell growth and ER-mediated transactivation can be inhibited
      with either ICI or 4-OH-Tam. In conclusion, our data indicate IGF-IR and ER
      interactions in the alphaT3-1 cell line, an in vitro model for the pituitary
      gonadotrophs, hereby suggesting a role of IGF-I in the regulation of gonadotropin
      synthesis and secretion.

PMID- 17458896
TI  - Bicarbonate-dependent pH(i) regulation by chondrocytes within the superficial
      zone of bovine articular cartilage.
AB  - Control of chondrocyte pH (pH(i)) determines articular cartilage matrix
      metabolism. However, the transporters of chondrocytes in situ throughout
      cartilage zones are unclear, and we tested the hypothesis that chondocytes within
      the superficial zone (SZ) utilise a HCO(3) (-)-dependent system absent from other
      zones. Imaging of single BCECF-labelled cells was used to monitor the pH(i) of in
      situ chondrocytes within the cartilage zones, and also that of cells isolated
      from the SZ or full depth (FD) explants. Resting pH(i) and intrinsic buffering
      power (beta(i)) in HEPES-buffered saline was not different between SZ and DZ
      cells, however the pH(i) of SZ chondrocytes was lower in HCO(3) (-) saline.
      Ammonium pre-pulse was used to acid-load cells and pH(i) recovery by in situ or
      isolated SZ chondrocytes shown to be totally dependent on HCO(3) (-). pH(i)
      recovery rate was significantly (P < 0.05) greater for in situ cells, suggesting
      that isolation damaged the HCO(3) (-)-dependent system. Recovery of pH(i) by in
      situ cells was blocked by the anion transport inhibitor DIDS, and partially
      inhibited by EIPA probably non-specifically. Recovery of pH(i) by acidified MZ or
      DZ cells or those isolated from FD explants was not affected by HCO(3) (-) (P >
      0.05). Na(+)-dependent HCO(3) (-)-(NBC) transporters were identified in SZ
      chondrocytes by fluorescence immunohistochemistry suggesting that this system
      might account for the HCO(3) (-)-dependent recovery of pH(i). Bovine articular
      cartilage chondrocytes possess a HCO(3) (-)-dependent transporter which plays a
      key role in pH(i) regulation in cells in the SZ, but not in chondrocytes within
      deeper cartilage zones.

PMID- 17458897
TI  - Accelerated and safe expansion of human mesenchymal stromal cells in animal serum
      free medium for transplantation and regenerative medicine.
AB  - Human bone marrow mesenchymal stromal cells (hMSC) are currently investigated for
      a variety of therapeutic applications. However, most expansion protocols still
      use fetal calf serum (FCS) as growth factor supplement which is a potential
      source of undesired xenogeneic pathogens. We established an expansion protocol
      for hMSC based on the use of GMP-produced basic medium LP02 supplemented with 5%
      of platelet lysate (PL) obtained from human thrombocyte concentrates. Compared to
      FCS-supplemented culture conditions, we found a significant increase in both
      colony forming unit-fibroblast (CFU-F) as well as cumulative cell numbers after
      expansion. This accelerated growth is optimized by pooling of at least 10
      thrombocyte concentrates. A minimal requirement is the use of 5% of PL with an
      optimal platelet concentration of 1.5 x 10(9)/ml, and centrifugation of thawed
      lysate at high speed. Cells expanded by this protocol meet all criteria for
      mesenchymal stromal cells (MSCs), e.g. plastic adherence, spindle-shaped
      morphology, surface marker expression, lack of hematopoietic markers, and
      differentiation capability into three mesenchymal lineages. MSC at passage 6 were
      cytogenetically normal and retained their immune-privileged potential by
      suppressing allogeneic reaction of T-cells. Additionally, gene expression
      profiles show increased mRNA levels of genes involved in cell cycle and DNA
      replication and downregulation of developmental and differentiation genes,
      supporting the observation of increased MSC-expansion in PL-supplemented medium.
      In summary, we have established a GMP-compatible protocol for safe and
      accelerated expansion of hMSC to be used in cell and tissue therapy.

PMID- 17458898
TI  - Maspin augments proteasome inhibitor-induced apoptosis in prostate cancer cells.
AB  - Proteasome inhibitors are known to induce apoptosis in a variety of cancer cells.
      On the other hand, maspin, a non-inhibitory serine protease inhibitor, is shown
      to sensitize cancer cells to therapeutic agents that induce apoptosis. We
      examined the consequence of maspin expression in prostate cancer cells targeted
      for treatment with various proteasome inhibitors. We observed that proteasome
      inhibitors induced apoptosis more effectively in maspin transfected human
      prostate cancer DU145 cells than in control cells. Interestingly, increased
      apoptosis in these cells was associated with a significant induction of maspin
      expression. MG-132, a proteasome inhibitor, induced endogenous and ectopic
      [cytomegalovirus promoter (CMV)-driven] maspin expression, and maspin siRNA
      attenuated MG-132-induced apoptosis. Proteasome inhibitor-induced maspin
      expression was inhibited by actinomycin D (Act D) and cyclohexamide (CHX), and by
      the inhibitors of p38MAPK, but not ERK1/2 or NF-kappaB. Electrophoretic mobility
      shift assay (EMSA) and promoter-reporter activity analyses suggested that p38MAPK
      activated transcription factor AP-1 is responsible for proteasome inhibitor
      induced maspin expression. Taken together, these observations demonstrate that
      proteasome inhibitors induce maspin expression by activating p38MAPK pathway, and
      that maspin thus expressed, in turn, augments proteasome inhibitor-induced
      apoptosis in prostate cancer cells. Our results suggest that gene therapy
      involving ectopic maspin expression may dramatically improve the efficacy of
      proteasome inhibitors for the treatment of prostate cancer.

PMID- 17458899
TI  - Prostate carcinoma cells selected by long-term exposure to reduced oxygen tension
      show remarkable biochemical plasticity via modulation of superoxide, HIF-1alpha
      levels, and energy metabolism.
AB  - Cancer cells are able to tolerate levels of O(2) that are damaging or lethal to
      normal cells; we hypothesize that this tolerance is the result of biochemical
      plasticity which maintains cellular homeostasis of both energy levels and
      oxidation state. In order to examine this hypothesis, we used different O(2)
      levels as a selective agent during long-term culture of DU145 prostate cancer
      cells to develop three isogenic cell lines that grow in normoxic (4%), hyperoxic
      (21%), or hypoxic (1%) O(2) conditions. Growth characteristics and O(2)
      consumption differed significantly between these cell lines without changes in
      ATP levels or altered sensitivity to 2-deoxy-D-glucose, an inhibitor of
      glycolysis. O(2) consumption was significantly higher in the hyperoxic line as
      was the level of endogenous superoxide. The hypoxic cell line regulated the
      chemical gradient of the proton motive force (PMF) independent of the electrical
      component without O(2)-dependent changes in Hif-1alpha levels. In contrast, the
      normoxic line regulated Hif-1alpha without tight regulation of the chemical
      component of the PMF noted in the hypoxic cell line. From these studies, we
      conclude that selection of prostate cancer cells by long-term exposure to low
      ambient levels of O(2) resulted in cells with unique biochemical properties in
      which energy metabolism, reactive oxygen species (ROS), and HIF-1alpha levels are
      modulated to allow cell survival and growth. Thus, cancer cells exhibit
      remarkable biochemical plasticity in response to various O(2) levels.

PMID- 17458900
TI  - Ceramide inhibits LPS-induced production of IL-5, IL-10, and IL-13 from mast
      cells.
AB  - Mast cells are central regulators of allergic inflammation through production of
      various chemical mediators and cytokines. Bacterial infection occasionally
      worsens allergic inflammation. Although the exact mechanism of this phenomenon
      remains unclear, we have previously reported that LPS stimulates mast cells to
      produce not only pro-inflammatory cytokines, such as IL-6 and TNF-alpha, but also
      Th2-type cytokines, such as IL-5 and IL-13, and a regulatory cytokine, IL-10. In
      the present study, we have studied the effect of ceramide on LPS-mediated
      cytokine production from mast cells, as ceramide modulates various cellular
      functions in many cell types. Administration of cell-permeable C8 ceramide
      reduced production of IL-5, IL-10, and IL-13 from LPS-stimulated mouse bone
      marrow-derived mast cells (BMMCs) apparently through transcriptional inhibition,
      but did not affect IL-6 or TNF-alpha production. Consistently, LPS-stimulated
      production of IL-5, IL-10, and IL-13 from BMMCs is significantly enhanced in the
      presence of fumonisin B1, a de novo ceramide synthesis inhibitor. Interestingly,
      the same C8 ceramide treatment showed opposite effects on cytokine production
      from LPS-stimulated macrophages, reducing IL-6 and TNF-alpha while not affecting
      IL-10 production. C8 ceramide pretreatment significantly reduced LPS-induced Akt
      phosphorylation in BMMCs, but not in macrophages. Furthermore, pretreatment of
      BMMCs by wortmannin, a specific inhibitor of PI3 kinase, inhibited LPS-stimulated
      expression of IL-5, IL-10, and IL-13, but not that of TNF-alpha or IL-6. Thus,
      ceramide appeared to down-regulate LPS-stimulated production of IL-5, IL-10, and
      IL-13 from mast cells by inhibiting PI3 kinase-Akt pathway in a cell type
      specific manner.

PMID- 17458901
TI  - Psychosine-induced apoptosis and cytokine activation in immune peripheral cells
      of Krabbe patients.
AB  - Globoid cell leukodystrophy or Krabbe disease (KD), is a hereditary disorder
      caused by galactosylceramidase deficiency. Progressive accumulation of psychosine
      is considered to be the critical pathogenetic mechanism of cell death in the
      Krabbe brain. Psychosine mechanism of action has not been fully elucidated. It
      seems to induce apoptosis in oligodendrocytes through a mitochondrial pathway and
      to up-regulate inflammatory cytokines production resulting in oligodendrocyte
      loss. Our aim was to evaluate the role of psychosine in apoptotic cell death and
      inflammatory response in a group of patients affected by KD using peripheral
      blood lymphocytes (PBLs) and peripheral blood mononuclear cells (PBMCs) as a
      cellular model. PBLs from KP and healthy controls were exposed to 20 microM
      psychosine and analysed by flow cytometry, agarose gel electrophoresis and
      fluorescence microscopy. Our results showed that psychosine induces apoptosis in
      PBLs through a mitochondrial pathway, but the apoptotic response was quite low
      especially KP. The role of psychosine in the up-regulation of cytokines
      (TNFalpha, IL8 and MCP1) has been evaluated by ELISA in PBMCs from KP and
      controls after stimulation with LPS and phytohemagglutinin. Both in basal
      condition and after LPS stimulation, cells from KP showed a significant increase
      in TNF-alpha production, reduced MCP1 levels and no modification in IL8. These
      results indicate that lymphomonocytes from KP had a basal proinflammatory pattern
      that was amplified by psychosine. In conclusion, the reduced apoptotic response
      and the atypical cytokine production observed in our experiments, suggest an
      involvement of inflammatory pattern in immune peripheral cells of KP.

PMID- 17458902
TI  - IGF-I plus E2 induces proliferation via activation of ROS-dependent ERKs and JNKs
      in human breast carcinoma cells.
AB  - Induction of 17beta-estradiol (E2) and insulin-like growth factor-I (IGF-I) has
      been detected in breast carcinoma, however the interaction between E2 and IGF-I
      in the proliferation of breast carcinoma cells is still unclear. In the present
      study, we found that IGF-I enhances the E2-induced proliferation in MCF-7 human
      breast carcinoma cells in accordance with stimulation of colony formation via a
      soft agar assay. Activation of insulin receptor substrate-1 (IRS-1) protein and
      extracellular signal-related kinases (ERKs) and c-Jun N-terminal kinases (JNKs),
      but not p38 mitogen-activated protein kinase (MAPK), via phosphorylation
      induction was detected in MCF-7 cells treated with IGF-I plus E2 (E2/IGF-I).
      E2/IGF-I-induced proliferation was blocked by chemical inhibitors of ERKs
      (PD98059) and JNKs (SP600125). An increase in the expression of c-Jun protein was
      detected in E2/IGF-I-treated MCF-7 cells, and this was inhibited by PD98059 and
      SP600125. Transfection of the dominant negative MEKK and JNK plasmids
      significantly reduced E2/IGF-I-induced proliferation with suppression of c-Jun
      protein expression. An increase in peroxide production was detected in E2/IGF-I
      treated cells, and N-acetyl-L-cysteine (NAC) and Tiron (TIR) addition
      significantly inhibited E2/IGF-I-induced cell proliferation with blocking of the
      phosphorylation of ERKs and JNKs, and the expression of c-Jun protein.
      Additionally, 3-OH flavone, baicalein, and quercetin showed effective inhibitory
      activities against E2/IGF-I-induced proliferation through suppressing
      proliferative events such as phosphorylation of IRS-1, ERKs, and JNKs proteins,
      and induction of c-Jun protein and colony formation. These results indicate that
      IGF-I interacts with E2 to promote the proliferation of breast carcinoma cells
      via ROS-dependent MAPK activation and c-Jun protein expression. The structure
      related inhibition of E2/IGF-I-induced proliferative events by flavonoids is
      elucidated.

PMID- 17458903
TI  - Effects of different magnitudes of cyclic stretch on Na+-K+-ATPase in skeletal
      muscle cells in vitro.
AB  - The Na(+)-K(+)-ATPase, which plays a major role in modulation of skeletal muscle
      excitability and contractility, is one of the marker enzymes that senses the
      mechanical strain and adapts to the stimuli. Although many papers had been
      published on the effects of mechanical stress on Na(+)-K(+)-ATPase in aortic
      smooth muscle cells, little was known about the effects of different magnitudes
      of mechanical stretch on Na(+)-K(+)-ATPase in skeletal muscle cells. In the
      present study, we determined the effect of different magnitudes(6%, 12%, or 25%
      elongation) of cyclic stretch on the activity of the Na(+)-K(+)-ATPase and
      investigated possible mechanisms that might be involved in the action of stretch.
      The results showed the application of different magnitudes of cyclic stretch
      induced a magnitude-dependent increase of Na(+)-K(+)-ATPase activity in cultured
      skeletal muscle cells. Furthermore, inhibition of ionic fluxes through SACs
      prevented the action of stretch on Na(+)-K(+)-ATPase activity. The stretch
      induced increase in Na(+)-K(+)-ATPase activity was not blocked by Actinomycin D.
      No significant changes in mRNA and total cell protein levels of Na(+)-K(+)-ATPase
      were detected after stretched continuous for 24 h. However, cyclic stretch
      increased cell surface expression of Na(+)-K(+)-ATPase alpha(1)- and alpha(2)
      subunit proteins by 1.3- and 1.75-fold, respectively, and the increases in Na(+)
      K(+)-ATPase activity and cell surface expression were abolished by LY-294002.
      These data indicated that cyclic stretch induced a "magnitude-dependent" increase
      of Na(+)-K(+)-ATPase activity in cultured skeletal muscle cells in vitro. The
      upregulation involved translocation of Na(+)-K(+)-ATPase alpha(1)- and alpha(2)
      subunits to plasma membrane, not increased gene transcription. These results
      suggested a novel nontranscriptional mechanism for regulation of Na(+)-K(+)
      ATPase in skeletal muscle cells by cyclic stretch.

PMID- 17458904
TI  - Canonical and non-canonical Wnts differentially affect the development potential
      of primary isolate of human bone marrow mesenchymal stem cells.
AB  - This study examines the role of Wnt signaling events in regulating the
      differential potential of mesenchymal stem cells (MSCs) from adult bone marrow
      (BM). Immunohistochemical analysis of BM revealed co-localization of Wnt5a
      protein, a non-canonical Wnt, with CD45(+) cells and CD45(-) STRO-1(+) cells,
      while Wnt3a expression, a canonical Wnt, was associated with the underlying
      stroma matrix, suggesting that Wnts may regulate MSCs in their niche in BM. To
      elucidate the role of Wnts in MSC development, adult human BM-derived mononuclear
      cells were maintained as suspension cultures to recapitulate the marrow cellular
      environment, in serum-free, with the addition of Wnt3a and Wnt5a protein. Results
      showed that Wnt3a increased cell numbers and expanded the pool of MSCs capable of
      colony forming unit -- fibroblast (CFU-F) and CFU -- osteoblast (O), while Wnt5a
      maintained cell numbers and CFU-F and CFU-O numbers. However, when cells were
      cultured directly onto tissue culture plastic, Wnt5a increased the number of CFU
      O relative to control conditions. These findings suggest the potential dual role
      of Wnt5a in the maintenance of MSCs in BM and enhancing osteogenesis ex vivo. Our
      work provides evidence that Wnts can function as mesenchymal regulatory factors
      by providing instructive cues for the recruitment, maintenance, and
      differentiation of MSCs.

PMID- 17458905
TI  - Biochemical characterization and modulation of LH/CG-receptor during human
      trophoblast differentiation.
AB  - Due to the key role of the human chorionic gonadotropin hormone (hCG) in
      placental development, the aim of this study was to characterize the human
      trophoblastic luteinizing hormone/chorionic gonadotropin receptor (LH/CG-R) and
      to investigate its expression using the in vitro model of human cytotrophoblast
      differentiation into syncytiotrophoblast. We confirmed by in situ immunochemistry
      and in cultured cells, that LH/CG-R is expressed in both villous cytotrophoblasts
      and syncytiotrophoblasts. However, LH/CG-R expression decreased during
      trophoblast fusion and differentiation, while the expression of hCG and hPL
      (specific markers of syncytiotrophoblast formation) increased. A decrease in
      LH/CG-R mRNA during trophoblast differentiation was observed by means of semi
      quantitative RT-PCR with two sets of primers. A corresponding decrease (
      approximately 60%) in LH/CG-R protein content was shown by Western-blot and
      immunoprecipitation experiments. The amount of the mature form of LH/CG-R,
      detected as a 90-kDa band specifically binding (125)I-hCG, was lower in
      syncytiotrophoblasts than in cytotrophoblasts. This was confirmed by Scatchard
      analysis of binding data on cultured cells. Maximum binding at the cell surface
      decreased from 3,511 to about 929 molecules/seeded cells with a kDa of 0.4-0.5
      nM. Moreover, on stimulation by recombinant hCG, the syncytiotrophoblast produced
      less cyclic AMP than cytotrophoblasts, indicating that LH/CG-R expression is
      regulated during human villous trophoblast differentiation.

PMID- 17458907
TI  - Laparoscopy and gallbladder cancer.

PMID- 17458906
TI  - Regulation of plasminogen activators in human thyroid follicular cells and their
      relationship to differentiated function.
AB  - Human thyroid cells in culture take up and organify (125)I when cultured in TSH
      (acting through cAMP) and insulin. They also secrete urokinase (uPA) and tissue
      type (tPA) plasminogen activators (5-100 IU/10(6)cells/day). TSH and insulin both
      decreased secreted PA activity (PAA), uPA and tPA protein and their mRNAs.
      Autocrine fibroblast growth factor increased secreted PAA and inhibited thyroid
      cell (125)I uptake. Epidermal growth factor (EGF) and the protein kinase C (PKC)
      activator, TPA significantly increased PAA and inhibited thyroid differentiated
      function, (TPA > EGF). For TPA, effects were rapid, increased PAA secretion and
      decreased (125)I uptake being seen at 4 h whereas for EGF, a 24 h incubation was
      required. qRT-PCR showed significantly increased mRNA expression of uPA with
      lesser effects on tPA. Aprotinin, which inhibits PAA, increased (125)I uptake but
      did not abrogate the effects of TPA and EGF. The MEKK inhibitor, PD98059
      partially reversed the effects of EGF and TPA on PAA, and largely reversed the
      effects of EGF but not TPA on differentiated function. PKC inhibitors
      bisindoylmaleimide 1, and the specific PKCbeta inhibitor, LY379196 completely
      reversed the effects of TPA on (125)I uptake and PAA whereas EGF effects were
      unaffected. TPA inhibited follicle formation and this effect was blocked by
      LY379196 but not PD98059. We conclude that in thyroid cells, MAPK activation
      inversely correlates with (125)I uptake and directly correlates with PA
      expression, in contrast to the effects of cAMP. TPA effects on iodide metabolism,
      dissolution of follicles and uPA synthesis are mediated predominantly through
      PKCbeta whereas EGF exerts its effects through MAPK but not PKCbeta.

PMID- 17458908
TI  - Feasibility study of adjustment for contamination and non-compliance in a
      prostate cancer screening trial.
AB  - BACKGROUND: The use of PSA as a screening test has become increasingly prevalent
      in the general population and therefore also in the control arm of the European
      Randomized study of Screening for Prostate Cancer (ERSPC). We present a
      feasibility study and impact simulation of a secondary analysis, which imitates a
      situation where all participants in the study are managed according to their
      random assignment. METHODS: The results of the Rotterdam section of the ERSPC
      were adjusted for contamination and non-compliance according to Cuzick et al.
      [Stat Med 1997; 16:1017-1029]. Endpoints of this analysis were simulated
      reductions in prostate cancer mortality. RESULTS: Of the men allocated to the
      screen arm, 27.1% were non-compliant. In the control arm 30.7% had their PSA
      level measured by a general practitioner (GP) (i.e., contamination). For a
      scenario in which the intention-to-screen analysis was assumed to give a decrease
      in the mortality in the men randomized to screening of 6.7%, the secondary
      analysis resulted in a decrease of 16.1% for those actually screened. CONCLUSION:
      Although the definition of contamination as "PSA ever tested" gives an indication
      of the proportion of contamination, it will be important to differentiate the
      screening use of PSA from its diagnostic use. For the rest, adjustment for non
      compliance and contamination was shown to be feasible in this prostate cancer
      screening trial. It can therefore be used to carry out a secondary analysis on
      the definitive outcome of the ERSPC and will provide accurate information for
      those men who are in fact screened.

PMID- 17458909
TI  - Inverted, stapled J-pouch free jejunal transfer for reconstruction of the pharynx
      and esophagus.
AB  - Since the advent of the jejunal free flap in the early 1900s, it has become one
      of the most effective and widely used methods for reconstruction of
      circumferential defects of the esophagus, often due to malignant disease.
      However, as esophageal resections extend further cranially, reconstruction
      becomes more difficult due to the size discrepancy between the proximal jejunum
      and the pharygostome. Several authors have described techniques to overcome this
      problem, although there is, as yet, no consensus on the most effective method.
      Here we present our experience with an inverted, stapled J-pouch free jejunal
      transfer, analogous to that used in the ileoanal anastomosis after
      proctocolectomy for the treatment of ulcerative colitis and familial polyposis
      coli. In the head and neck, the inverted J-pouch provides several advantages when
      a resection extends into the pharynx: a closer size match to the large pharyngeal
      defect, a reservoir to aid swallowing, and increased conduit size proximally to
      aid gravity-dependent swallowing in the presence of uncoordinated peristalsis and
      tongue resection. This technique has served as a safe, effective, and rapid
      operation for this complex reconstructive problem.

PMID- 17458910
TI  - Method of determination of the reticulocyte age distribution from flow cytometry
      count by a structured-population model.
AB  - BACKGROUND: A flow cytometry count of reticulocytes (RET) provides information
      about distribution of signal emitted by reticulocyte RNA. A new method of
      determination of the RNA degradation rate in RET is provided. This technique
      allows one to determinate the age distribution of RET. METHODS: The method is
      based on a series of flow cytometry counts of cultured RET. From those counts,
      the changes of signal distribution of RET over time are obtained. The RNA
      degradation rate of individual RET is then resolved based on changes in the
      signal distribution of the whole population of cells. The obtained relation
      between signal and age allows obtaining a RET age density that can be used to
      characterize RET age distribution and age dependence of processes that control
      the population dynamics. RESULTS: The total maturation time of RET in rats is 3
      days. The median time that a homeostatic RET spends in blood or before it becomes
      a mature RBC is about 0.6 days, whereas a stress RET needs 0.8 days. CONCLUSIONS:
      The proposed method provides means for studies in vivo RET dynamics using age
      structured models.

PMID- 17458911
TI  - Pharmaceutical strategy and innovation: an academics perspective.
AB  - The pharmaceutical industry is under increasing pressure on many fronts, from
      investors requiring larger returns to consumer groups and health authorities
      demanding cheaper and safer drugs. It is also feeling additional pressure from
      the infringement upon its profit margins by generic drug producers. Many
      companies are aggressively pursuing outsourcing contracts in an attempt to
      counter many of the financial pressures and streamline their operations. At the
      same time, the productivity of the pharmaceutical industry at its science base is
      being questioned in terms of the number of products and the timeframes required
      for each company to deliver them to market. This has generated uncertainties
      regarding the current corporate strategies that have been adopted and the levels
      of innovation being demonstrated. In this essay we discuss these topics in the
      context of the global pharmaceutical market, investigating the basis for many of
      these issues and highlighting the hurdles the industry needs to overcome,
      especially as they relate to the chemical sciences.

PMID- 17458912
TI  - Increased single-nucleotide discrimination in allele-specific polymerase chain
      reactions through primer probes bearing nucleobase and 2'-deoxyribose
      modifications.
AB  - The diagnosis of genetic dissimilarities between individuals is becoming
      increasingly important due to the discovery that these variations are related to
      complex phenotypes like the predisposition to certain diseases or compatibility
      with drugs. The most common among these sequence variations are single-nucleotide
      polymorphisms (SNPs). The availability of reliable and efficient methods for the
      interrogation of the respective genotypes is the basis for any progress along
      these lines. Many methods for the detection of nucleotide variations in genes
      exist, in which amplification of the target gene is required before analysis can
      take place. The allele-specific polymerase chain reaction (asPCR) combines target
      amplification and analysis in a single step. The principle of asPCR is based on
      the formation of matched or mismatched primer-target complexes. The most
      important parameter in asPCR is the discrimination of these matched or mismatched
      pairs. In recent publications we have shown that the reliability of SNP detection
      through asPCR is increased by employing chemically modified primer probes. In
      particular, primer probes that bear a polar 4'-C-methoxymethylene residue at the
      3' end have superior properties in discriminating single-nucleotide variations by
      PCR. Here we describe the synthesis of several primer probes that bear nucleobase
      modifications in addition to the 4'-C-methoxymethylenated 2'-deoxyriboses. We
      studied the effects of these alterations on single-nucleotide discrimination in
      allele-specific PCR promoted by a DNA polymerase and completed these results with
      single-nucleotide-incorporation kinetic studies. Moreover, we investigated
      thermal denaturing of the primer-probe-template complexes and recorded circular
      dichroism (CD) spectra for inspecting the thermodynamic and photophysical duplex
      behaviour of the introduced modifications. In short, we found that primer probes
      bearing a 4'-C-methoxymethylene residue at the 2'-deoxyribose moiety in
      combination with a thiolated thymidine moiety have synergistic effects and
      display significantly increased discrimination properties in asPCR.

PMID- 17458913
TI  - Heat-induced alterations in the surface population of metal sites in bimetallic
      nanoparticles.
AB  - The ability to alter the surface population of metal sites in bimetallic
      nanoparticles (NPs) is of great interest in the context of heterogeneous
      catalysis. Here, we report findings of surface alterations of Pt and Ru metallic
      sites in bimetallic carbon-supported (PtRu/C) NPs that were induced by employing
      a controlled thermal-treatment strategy. The thermal-treatment procedure was
      designed in such a way that the particle size of the initial NPs was not altered
      and only the surface population of Pt and Ru was changed, thus allowing us to
      deduce structural information independent of particle-size effects. X-ray
      absorption spectroscopy (XAS) was utilized to deduce the structural parameters
      that can provide information on atomic distribution and/or extent of alloying as
      well as the surface population of Pt and Ru in PtRu/C NPs. The PtRu/C catalyst
      sample was obtained from Johnson Matthey, and first the as-received catalyst was
      reduced in 2 % H2 and 98 % Ar gas mixture at 300 degrees C for 4 h (PtRu/C as
      reduced). Later this sample was subjected to thermal treatment in either oxygen
      (PtRu/C-O2-300) or hydrogen (PtRu/C-H2-350). The XAS results reveal that when the
      as-reduced PtRu/C catalyst was exposed to the O2 thermal-treatment strategy, a
      considerable amount of Ru was moved to the catalyst surface. In contrast, the H2
      thermal-treatment strategy led to a higher population of Pt on the PtRu/C
      surface. Characterization of the heat-treated PtRu/C samples by X-ray diffraction
      and transmission electron microscopy reveals that there is no significant change
      in the particle size of thermally treated samples when compared to the as
      received PtRu/C sample. The electrochemical properties of the as-reduced and heat
      treated PtRu/C catalyst samples were confirmed by cyclic voltammetry, CO
      adsorption stripping voltammetry, and linear sweep voltammetry. Both XAS and
      electrochemical investigations concluded that the PtRu/C-H2-350 sample exhibits
      significant enhancement in reactivity toward methanol oxidation as a result of
      the increased surface population of the Pt when compared to the PtRu/C-O2-300 and
      PtRu/C as-reduced samples.

PMID- 17458914
TI  - Ultrahigh-throughput screening to identify E. coli cells expressing functionally
      active enzymes on their surface.
AB  - We show here that E. coli bacteria that display esterases or lipases on their
      cell surface together with horseradish peroxidase (HRP) are capable of
      hydrolysing carboxylic acid esters of biotin tyramide. The tyramide radicals
      generated by the coupled lipase-peroxidase reaction were short-lived and
      therefore became covalently attached to reactive tyrosine residues that were
      located in close vicinity on the surface of a bacterial cell that displayed
      lipase activity. Up to 120 000 biotinylated tyramide derivatives could be
      covalently coupled through HRP activation to the surface of a single living E.
      coli cell. Differences in cellular esterase activity were found to correlate with
      the amount of biotin tyramide deposited on the cell surface. Selective biotin
      tyramide labelling of cells that had lipase activity allowed their isolation by
      magnetic cell sorting from a 1:10(6) mixture of control cells. This strategy of
      covalently attaching a biotin label to esterase-proficient bacteria might open
      new avenues to ultrahigh-throughput screening of enzyme libraries for hydrolytic
      enzymes with enhanced activities or enantioselectivities.

PMID- 17458915
TI  - Evidence for a role of the membrane-proximal region of herpes simplex virus type
      1 glycoprotein H in membrane fusion and virus inhibition.
AB  - We have identified a putative membrane-interacting domain preceding the
      transmembrane domain of the Herpes simplex virus type 1 (HSV-1) glycoprotein H
      (gH). Peptides derived from this region interact strongly with membranes and show
      a high tendency to partition at the interface. This region is predicted to bind
      at the membrane interface by adopting an alpha helical structure. Peptides
      representing either the HSV-1 gH pretransmembrane region or a scrambled control
      with a different hydrophobic profile at the point of interface have been studied.
      The peptides derived from this domain of gH induce the fusion of liposomal
      membranes, adopt helical conformations in membrane mimetic environments and are
      able to inhibit HSV-1 infectivity. The pretransmembrane region appears to be a
      common feature in viral fusion proteins of several virus families, and such a
      feature might be related to their fusogenic function. The identification of
      membrane-interacting regions capable of modifying the biophysical properties of
      phospholipid membranes lends weight to the view that such domains might function
      directly in the fusion process and could facilitate the future development of HSV
      1 entry inhibitors.

PMID- 17458916
TI  - In situ generation of chiral N-dienyl lactams in a multicomponent reaction: an
      efficient and highly selective way to asymmetric amidocyclohexenes.
AB  - Chiral N-dienyl lactams are crucial building blocks for the synthesis of complex
      organic compounds. However, their generation is rather challenging. This paper
      reports on a highly efficient and diastereoselective multicomponent methodology
      utilizing chiral amides, aldehydes, and dienophiles (AAD reaction). The three
      components readily react under in situ generation of chiral N-dienyl lactams
      which undergo a subsequent Diels-Alder reaction. Different chiral amides have
      been employed in the standard protocol delivering yields up to 94%, and
      selectivities up to 90% de. Moreover, DFT calculations were performed to explain
      the obtained selectivities.

PMID- 17458917
TI  - On the tacticity of polynorbornenes with 5,6-endo pendant groups that contain
      substituted aryl chromophores.
AB  - Two dimers and a series of polymers with 5,6-endo pendant aryl groups that
      contain different substituents at the para positions were synthesized. The
      conformation and stereochemistry of the dimers and polymers were determined by
      nonlinear optical analysis (EFISH) as well as UV/Vis and 13C NMR spectroscopy.
      The chemical shifts of C7 for the polymers appeared as two peaks in the 13C NMR
      spectra when the substituents are electron-withdrawing groups. The percentage
      decrease in the relative extinction coefficient of the polymers, epsilon(d), was
      linearly related to the Hammett constant sigma. Polynorbornenes with electron
      withdrawing substituents may adopt isotactic stereochemistry with all pendant
      groups aligned in one direction. The nature of the interactions between
      neighboring chromophores may be one of the most important factors in directing
      the stereoregularity and conformation of these polymers. The corresponding
      polymers derived from the exo isomers appeared to be less stereoregular.

PMID- 17458918
TI  - MRS quality assessment in a multicentre study on MRS-based classification of
      brain tumours.
AB  - This paper reports on quality assessment of MRS in the European Union-funded
      multicentre project INTERPRET (International Network for Pattern Recognition of
      Tumours Using Magnetic Resonance; http://azizu.uab.es/INTERPRET), which has
      developed brain tumour classification software using in vivo proton MR spectra.
      The quality assessment consisted of both MR system quality assurance (SQA) and
      quality control (QC) of spectral data acquired from patients and healthy
      volunteers. The system performance of the MR spectrometers at all participating
      centres was checked bimonthly by a short measurement protocol using a specially
      designed INTERPRET phantom. In addition, a more extended SQA protocol was
      performed yearly and after each hardware or software upgrade. To compare the
      system performance for in vivo measurements, each centre acquired MR spectra from
      the brain of five healthy volunteers. All MR systems fulfilled generally accepted
      minimal system performance for brain MRS during the entire data acquisition
      period. The QC procedure of the MR spectra in the database comprised automatic
      determination of the signal-to-noise ratio (SNR) in a water-suppressed spectrum
      and of the line width of the water resonance (water band width, WBW) in the
      corresponding non-suppressed spectrum. Values of SNR > 10 and WBW < 8 Hz at 1.5 T
      were determined empirically as conservative threshold levels required for spectra
      to be of acceptable quality. These thresholds only hold for SNR and WBW values
      using the definitions and data processing described in this article. A final QC
      check consisted of visual inspection of each clinically validated water
      suppressed metabolite spectrum by two, or, in the case of disagreement, three,
      experienced MR spectroscopists, to detect artefacts such as large baseline
      distortions, exceptionally broadened metabolite peaks, insufficient removal of
      the water line, large phase errors, and signals originating from outside the
      voxel. In the end, 10% of 889 spectra with completed spectroscopic judgement were
      discarded.

PMID- 17458919
TI  - Effects of AZD2171 and vandetanib (ZD6474, Zactima) on haemodynamic variables in
      an SW620 human colon tumour model: an investigation using dynamic contrast
      enhanced MRI and the rapid clearance blood pool contrast agent, P792
      (gadomelitol).
AB  - The effect of two novel therapeutic agents on tumour haemodynamics was
      investigated using a fast dynamic contrast-enhanced (DCE)-MRI protocol (0.5
      s/image) sensitive to signal changes in both the vascular input function and
      tumour during the administration of the macromolecular rapid clearance blood pool
      agent (MM-RCBPA), gadomelitol (P792, Vistarem). This enabled simultaneous
      measurement of the tumour blood flow per unit volume of tissue (F/V(T), mL/s/mL),
      the fractional plasma volume (V(p), %), and the permeability surface area product
      per unit volume of tissue (PSrho, s(-1)) in subcutaneous SW620 human colorectal
      tumour xenografts grown in nude rats before and after (at 0 and 22 h; imaging at
      24 h) acute treatment with AZD2171 (3 mg/kg) and vandetanib (ZD6474, Zactima; 50
      mg/kg), which have inhibitory activity against vascular endothelial growth factor
      receptor-2 (VEGFR-2) tyrosine kinase. MRI was performed at 4.7 T using a single
      slice, modified, T(1)-weighted, spoiled gradient-echo technique. Both compounds
      reduced gadomelitol uptake into the tumour. AZD2171 and vandetanib, respectively,
      (a) greatly reduced PSrho to 19.7 +/- 9.5% and 28.9 +/- 14.1% of baseline (P =
      0.007 and P = 0.02), (b) markedly reduced V(p) to 31.2 +/- 19.1% and 54.8 +/-
      21.2% of baseline (P = 0.015 and P = 0.09), and (c) had no significant effect on
      F/V(T). There was no significant difference between groups treated with AZD2171
      and vandetanib when each variable was compared. The reductions in PSrho and V(p)
      are consistent with inhibition of VEGF signalling. AZD2171 (3 mg/kg) and
      vandetanib (50 mg/kg) were also found to produce a comparable chronic inhibition
      of SW620 tumour growth (89% for both). This study shows that DCE-MRI using an MM
      RCPBA can be used to distinguish tumour vascular flow, volume, and permeability
      surface area product in a tumour model, and enables the acute effects of VEGF
      signalling inhibition to be examined in detail.

PMID- 17458920
TI  - Amidine analogues of melphalan: synthesis, cytotoxic activity, and DNA binding
      properties.
AB  - Design, synthesis, and cytotoxic activity of amidine derivatives of melphalan are
      described and structure-activity relationships are discussed. Evaluation of the
      cytotoxicity of these compounds employing a MTT assay and inhibition of
      [(3)H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 human breast
      cancer cells demonstrated that these compounds were more active than melphalan.
      Data from the ethidium displacement assay showed that these compounds were able
      to bind in the minor groove-binding mode in AT sequences of DNA. The cytotoxic
      properties of the amidine analogues of melphalan towards cultured human breast
      cancer cells correlate with topoisomerase II inhibitory properties but not with
      DNA-binding properties.

PMID- 17458921
TI  - Elevating tensor rank increases anisotropy in brain areas associated with intra
      voxel orientational heterogeneity (IVOH): a generalised DTI (GDTI) study.
AB  - Rank-2 tensors are unable to represent multi-modal diffusion associated with
      intra-voxel orientational heterogeneity (IVOH), which occurs where axons are
      incoherently oriented, such as where bundles intersect or diverge. Under this
      condition, they are oblate or spheroidally shaped, resulting in artefactually low
      anisotropy, potentially masking reduced axonal density, myelinisation and
      integrity. Higher rank tensors can represent multi-modal diffusion, and suitable
      metrics such as generalised anisotropy (GA) and scaled entropy (SE) have been
      introduced. The effect of tensor rank was studied through simulations, and
      analysing high angular resolution diffusion imaging (HARDI) data from two
      volunteers, fit with rank-2, rank-4 and rank-6 tensors. The variation of GA and
      SE as a function of rank was investigated through difference maps and region of
      interest (ROI)-based comparisons. Results were correlated with orientation
      distribution functions (ODF) reconstructed with q-ball, and with colour-maps of
      the principal and second eigenvectors. Simulations revealed that rank-4 tensors
      are able to represent multi-modal diffusion, and that increasing rank further has
      a minor effect on measurements. IVOH was detected in subcortical regions of the
      corona radiata, along the superior longitudinal fasciculus, in the radiations of
      the genu of the corpus callosum, in peritrigonal white matter and along the
      inferior fronto-occipital and longitudinal fascicula. In these regions, elevating
      tensor rank increased anisotropy. This was also true for the corpus callosum,
      cingulum and anterior limb of the internal capsule, where increasing tensor rank
      resulted in patterns that, although mono-modal, were more anisotropic. In these
      regions the second eigenvector was coherently oriented. As rank-4 tensors have
      only 15 distinct elements, they can be determined without acquiring a large
      number of directions. By removing artefactual underestimation of anisotropy,
      their use may increase the sensitivity to pathological change.

PMID- 17458922
TI  - Impact of cancer on Moslem patients in Morocco.
AB  - BACKGROUND: The study aims to determine the impact of cancer on Moroccan patients
      of Moslem faith. METHOD: Patients included a convenience sample with histological
      confirmed cancer. Cases with cerebral metastasis or lacking capacity were
      excluded. Participants were assessed prospectively using a questionnaire covering
      epidemiological and socio-economic characteristics, religious affiliation,
      repercussions of disease on religious beliefs and practices. RESULTS AND
      CONCLUSIONS: One thousand and six hundred patients (median age 49 years) were
      approached; 41% females and 74% from rural areas. There was a high rate of
      illiteracy (38%) and only 7% had higher education. Seventeen per cent were
      divorced, among whom 41% were divorced after diagnosis of cancer. Eighty-seven
      per cent had no medical insurance. All were Muslims; 49% practising believers and
      51% non-practising. In the first group cancer represented a divine test that
      permitted acceptance of the disease. In the second group of 'non-practising
      believers', patients reported a feeling of culpability and 95% of them started
      taking up religious practices, often with extremism and sometimes in
      contradiction of medical advice. In both groups new behaviours were noticed; 450
      women now wore the 'Hijab' (scarf), 19% used popular medicine and plants in their
      diet recommended by the Koran. While these results require replication they
      indicate changes in behaviour by those within the Moslem faith following a cancer
      diagnosis.

PMID- 17458923
TI  - A personal perspective on the Royal Statistical Society report of the working
      party on statistical issues in first-in-man studies.

PMID- 17458926
TI  - Fluorescent hybridization probes for sensitive and selective DNA and RNA
      detection.
AB  - We outline the different approaches taken by our group in the design of
      fluorescent hybridization sensors. Molecular beacons (MBs) and binary probes
      (BPs) using two dyes (2d-MB and 2d-BP, respectively) have been synthesized; these
      sensors serve as switches in emission upon binding to target biomolecules, such
      as DNA. These sensors allow for ratiometric fluorescence detection of
      polynucleotides (PNs) by visualization of the probes when bound to a target PN.
      Additionally, three-dye MBs (3d-MB) and BPs (3d-BP) have been developed, where an
      energy-transfer cascade is employed to decrease the overlap between the
      fluorophore emission spectra, resulting in a low direct excitation of the
      acceptor fluorophore. Pyrene-based MB (Py-MB) and BP (Py-BP), which possess the
      advantage of long fluorescence lifetimes, have also been synthesized. Time
      resolved fluorescence spectra (TRES) can be used to discriminate between short
      lived background fluorescence and long-lived fluorescence of the pyrene probes.
      This technique was demonstrated by time-resolving the signal of a Py-BP from the
      background fluorescence in Aplysia californica cell extracts.

PMID- 17458927
TI  - Biofriendly sol-gel processing for the entrapment of soluble and membrane-bound
      proteins: toward novel solid-phase assays for high-throughput screening.
AB  - The last decade has seen a revolution in the area of sol-gel-derived biomaterials
      since the demonstration that these materials can be used to encapsulate
      biological species such as enzymes, antibodies, and other proteins in a
      functional state. In particular, recent years have seen tremendous progress in
      the development of more "protein-friendly" sol-gel processing methods and their
      use for immobilization of delicate proteins, including key drug targets such as
      kinases and membrane-bound receptors. The latter example is particularly
      impressive, given the inherently low stability of membrane receptors and the need
      to stabilize an amphiphilic bilayer lipid membrane to maintain receptor function.
      In this Account, we provide an overview of the advances in biofriendly sol-gel
      processing methods developed in our research group and others and highlight
      recent accomplishments in the immobilization of both soluble and membrane-bound
      proteins, with particular emphasis on enzymes and membrane receptors that are
      drug targets. Emerging applications of sol-gel-entrapped proteins, focusing on
      the development platforms for high-throughput screening of small molecules, are
      also described.

PMID- 17458928
TI  - Electrochemistry: an important tool to study and create new sol-gel-derived
      materials.
AB  - Electrochemical methods can be used to study the structure and properties of sol
      gel-derived materials. In addition, they can be used to create new materials and
      nanostructures. In this Account, these methods and the resulting information and
      materials obtained from them are described.

PMID- 17458929
TI  - Mononuclear Cu-O2 complexes: geometries, spectroscopic properties, electronic
      structures, and reactivity.
AB  - Using interwoven experimental and theoretical methods, detailed studies of
      several structurally defined 1:1 Cu-O 2 complexes have provided important
      fundamental chemical information useful for understanding the nature of
      intermediates involved in aerobic oxidations in synthetic and enzymatic copper
      mediated catalysis. In particular, these studies have shed new light on the
      factors that influence the mode of O 2 coordination (end-on vs side-on) and the
      electronic structure, which can vary between Cu(II)-superoxo and Cu(III)-peroxo
      extremes.

PMID- 17458930
TI  - Viscoelastic behavior of cellulose acetate in a mixed solvent system.
AB  - The effect of increasing water composition on the rheological and microstructural
      behavior of a ternary cellulose acetate (CA)/N,N-dimethylacetamide (DMA)/water
      system is examined. Addition of water to the CA/DMA system results in enhanced
      steady shear viscosity and dynamic viscoelastic properties and ultimately to
      phase-separated gel formation. The changes in dynamic rheological behavior of the
      system during gelation correlate well with the combined solubility parameter
      (delta) and, in particular, the Hansen hydrogen-bonding solubility parameter
      index (delta(h)) of the solvent system, suggesting hydrogen-bonding interactions
      may be the major route initiating the sol-gel process. For all gels studied, the
      elastic modulus and the critical stress to yield shifts to higher values with
      increasing CA concentration and/or water content. In addition, the elastic
      modulus exhibits a power-law behavior with water content, with the same power-law
      exponent observed for gels containing different CA concentrations. Addition of
      water leads to formation of a denser gel network, as evidenced from direct
      visualization of the gel microstructure through confocal microscopy.

PMID- 17458931
TI  - Structure and functional properties of ulvan, a polysaccharide from green
      seaweeds.
AB  - With today's interest in novel renewable chemicals and polymers, the
      underexploited marine green algae belonging to species of Ulva and Entermorpha
      stimulated interest as sources of polysaccharides with innovative structure and
      functional properties. These algae are common on all seashores and can produce in
      time an important amount of biomass in nutrient-enriched waters. The major water
      soluble polysaccharide, ulvan, extracted from the cell wall represents about 8
      29% of the algae dry weight. The original physicochemical, rheological, and
      biological properties recently unraveled for this complex sulfated aldobiouronan
      open the way for novel potential applications.

PMID- 17458932
TI  - Dynamic light scattering and fluorescence study of the interaction between double
      stranded DNA and poly(amido amine) dendrimers.
AB  - The interaction between a cationic poly(amido amine) (PAMAM) dendrimer of
      generation 4 and double-stranded salmon sperm DNA in 10 mM NaBr solution has been
      investigated using dynamic light scattering (DLS) and steady-state fluorescence
      spectroscopy. The structural parameters of the formed aggregates as well as the
      complex formation process were studied in dilute solutions. When DNA is mixed
      with PAMAM dendrimers, it undergoes a transition from a semiflexible coil to a
      more compact conformation due to the electrostatic interaction present between
      the cationic dendrimer and the anionic polyelectrolyte. The DLS results reveal
      that one salmon sperm DNA molecule forms a discrete aggregate in dilute solution
      with several PAMAM dendrimers with a mean apparent hydrodynamic radius of 50 nm.
      These discrete complexes coexist with free DNA at low molar ratios of dendrimer
      to DNA, which shows that cooperativity is present in the complex formation. The
      formation of the complexes was confirmed by agarose gel electrophoresis
      measurements. DNA in the complexes was also found to be significantly more
      protected against DNase catalyzed digestion compared to free DNA. The number of
      dendrimers per DNA chain in the complexes was found to be approximately 35 as
      determined by steady-state fluorescence spectroscopy.

PMID- 17458933
TI  - Redox-active cellulose Langmuir-Blodgett films containing beta-carotene as a
      molecular wire.
AB  - Redox-active Langmuir-Blodgett (LB) films containing dihydrophytyl ferrocenoate
      (DFc) and beta-carotene (betaC) were fabricated by use of 6-O
      dihydrophytylcellulose (DHPC) as a matrix. A mixture of DFc-DHPC formed a stable
      monolayer. Atomic force microscopy images revealed that the DFc molecules were
      dispersed uniformly throughout the surface in the ratio DFc:DHPC = 2:8 at 30 mN m
      1. The DFc-DHPC monolayer was transferred successfully onto a substrate, yielding
      Y-type LB films. Cyclic voltammograms for the DFc-DHPC LB films on an indium tin
      oxide (ITO) electrode exhibited a well-defined surface wave. The voltammograms of
      the DFc-DHPC LB films exhibited 60-40% redox-active ferrocene moieties, whereas
      those of the DFc-DHPC-betaC LB films exhibited 90-70%. X-ray diffraction patterns
      indicated that the distance between layers was independent of betaC molecules
      incorporated into the LB films. Consequently, these results suggested that betaC
      can function as a molecular wire.

PMID- 17458934
TI  - Self-assembly of conjugated polymers and ds-oligonucleotides directed fractal
      like aggregates.
AB  - Highly ordered nanostructures between conjugated polymers and ds-oligonucleotides
      have been first fabricated by simply controlling the self-assembly processes,
      which shows a novel concept for fabricating fractal-like structures. The
      formation of polymer/DNA fractal-like aggregates is a diffusion-limited
      aggregation (DLA) process. The fractal dimension is independent of the
      polymer/DNA concentration but only related to the polymer/DNA charge ratio. More
      interestingly, the different fluorescent resonance energy transfer (FRET)
      behavior between the polymer and the DNA can be used to distinguish dsDNA from
      ssDNA.

PMID- 17458935
TI  - Enhanced resistance of polyelectrolyte multilayer microcapsules to pepsin erosion
      and release properties of encapsulated indomethacin.
AB  - Polyelectrolyte multilayer films were prepared through layer-by-layer (LbL) self
      assembly using polysaccharide sodium alginate (ALG) and chitosan (CHI). After
      incubation in an enzyme pepsin solution, the multilayer film was partially
      destroyed as detected by the decrease in fluorescent intensity because of the
      enzymatic degradation of CHI. The enzymatic desorption was also observed from the
      microcapsule wall made of the ALG/CHI multilayer film directly deposited on
      indomethacin (IDM) microcrystals through LbL self-assembly. After pepsin erosion,
      the IDM release from the microcapsules monitored by UV absorbance was obviously
      accelerated because of desorption. To enhance the stability of the ALG/CHI
      multilayer film to the enzymatic erosion, some physical and chemical methods were
      established to increase film thickness or to cross-link the polysaccharides
      within the film. Increasing the layer number and raising the deposition
      temperature effectively slowed down the enzymatic desorption and release rate.
      Especially, increasing deposition temperature was more effective because of
      producing a more perfect structure in the ALG/CHI multilayer film. Cross-linking
      the neighboring layers of ALG and CHI with 1-ethyl-3-(3-dimethylamino
      propyl)carbodiimide in the ALG/CHI multilayer film significantly reduced the
      enzymatic desorption and release rate. Therefore, increasing deposition
      temperature and cross-linking neighboring layers are effective methods to protect
      the multilayer film fabricated using LbL assembly from the enzymatic erosion and
      to prolong the release of the encapsulated drug.

PMID- 17458936
TI  - Surface modification of bacterial cellulose nanofibers for property enhancement
      of optically transparent composites: dependence on acetyl-group DS.
AB  - Bacterial cellulose (BC) nanofibers were acetylated to enhance the properties of
      optically transparent composites of acrylic resin reinforced with the nanofibers.
      A series of BC nanofibers acetylated from degree-of-substitution (DS) 0 to 1.76
      were obtained. X-ray diffraction profiles indicated that acetylation proceeded
      from the surface to the core of BC nanofibers, and scanning electron microscopy
      images showed that the volume of nanofibers increases by the bulky acetyl group.
      Since acetylation decreased the refractive index of cellulose, regular
      transmittance of composites comprised of 63% BC nanofiber was improved, and
      deterioration at 580 nm because of fiber reinforcement was suppressed to only
      3.4%. Acetylation of nanofibers changed their surface properties and reduced the
      moisture content of the composite to about one-third that of untreated composite,
      although excessive acetylation increased hygroscopicity. Furthermore, acetylation
      was found to reduce the coefficient of thermal expansion of a BC sheet from 3 x
      10(-6) to below 1 x 10(-6) 1/K.

PMID- 17458937
TI  - Determination of size and concentration of gold nanoparticles from UV-vis
      spectra.
AB  - The dependence of the optical properties of spherical gold nanoparticles on
      particle size and wavelength were analyzed theoretically using multipole
      scattering theory, where the complex refractive index of gold was corrected for
      the effect of a reduced mean free path of the conduction electrons in small
      particles. To compare these theoretical results to experimental data, gold
      nanoparticles in the size range of 5 to 100 nm were synthesized and characterized
      with TEM and UV-vis. Excellent agreement was found between theory and experiment.
      It is shown that the data produced here can be used to determine both size and
      concentration of gold nanoparticles directly from UV-vis spectra. Equations for
      this purpose are derived, and the precision of various methods is discussed. The
      major aim of this work is to provide a simple and fast method to determine size
      and concentration of nanoparticles.

PMID- 17458938
TI  - Systematic investigation of the sorption properties of polyurethane foams for
      organic vapors.
AB  - Polyurethane foams (PUFs) have long been used for the sampling of airborne
      organic pollutants. However, a comprehensive investigation of their sorption
      properties for various organic compounds is still lacking. Here we present a
      systematic sorption study for a diverse set of up to 100 compounds at
      temperatures between 15 and 95 degrees C, at various humidities, and for various
      types of PUFs. The results can be summarized as follows: The performance of PU
      ethers is not susceptible to the humidity of the sampled air. Variability between
      different types of PU-ethers is small, and the compound variability in the
      sorption constants as well as the enthalpies of sorption can accurately be
      described with linear free energy relationships (LFERs) presented in the text. PU
      esters revealed an inferior sorbent behavior as compared to PU-ethers: sorption
      was kinetically hindered and was affected by humidity. Sorption varied between
      different types of esters and prediction with LFERs was less accurate than for
      the ethers.

PMID- 17458939
TI  - Lipid profiling reveals glycerophospholipid remodeling in zymosan-stimulated
      macrophages.
AB  - Comprehensive lipid profiling by mass spectrometry provides comparative data on
      the relative distribution of individual glycerophospholipids within each of the
      major classes. Application of this method to the analysis of glycerophospholipid
      remodeling in murine primary resident peritoneal macrophages (RPMs) during
      zymosan phagocytosis reveals significant decreases in the levels of every major
      arachidonic acid (20:4)-containing species of phosphatidylcholine (GPCho) and in
      selected 20:4-containing phosphatidylinositol (GPIns) and phosphatidylglycerol
      (GPGro) species. No net changes in 20:4-containing phosphatidylethanolamine
      (GPEtn) species were detected. Pretreatment of RPMs with LPS resulted in subtle
      changes in the magnitude and kinetics of the response but had no effect on the
      overall pattern of zymosan-induced glycerophospholipid remodeling. Inhibition of
      prostaglandin (PG) synthesis with indomethacin reduced the magnitude of the
      changes in 20:4-containing diacyl but not alkyl acyl species. Blockade of 20:4
      reacylation with thimerosal had no effect on the magnitude of the zymosan-induced
      changes in GPCho, GPIns, or GPGro species but revealed decreases in the level of
      alkyl acyl GEtn species. RAW264.7 cells contain much lower levels of phospholipid
      20:4 than do RPMs and synthesize PGs poorly in response to zymosan. Pretreatment
      with granulocyte-macrophage colony stimulating factor, lipopolysaccharide, and
      interferon-gamma substantially increased the extent of 20:4 mobilization and PG
      synthesis in these cells. However, under conditions of maximal zymosan-dependent
      PG synthesis, the only glycerophospholipid that exhibited a significant change
      was a 20:4-containing plasmenyl GPEtn. These results suggest that GPCho is the
      major ultimate source of 20:4 that is mobilized in zymosan-stimulated RPMs but
      that 20:4 mobilization may involve the intermediate turnover of alkyl acyl GPEtn
      species.

PMID- 17458940
TI  - Kinetic analysis of heparin and glucan sulfates binding to P-selectin and its
      impact on the general understanding of selectin inhibition.
AB  - P-Selectin, expressed on activated endothelial cells and platelets, is a high
      kinetic adhesion receptor involved in leukocyte rolling of the inflammatory
      response, or in tumor cell binding in the course of metastasis. Thus, P-selectin
      inhibition is a promising therapeutic target. The anti-inflammatory and anti
      metastatic activities of heparin have partly been related to the inhibition of P
      selectin binding. Here we apply a quartz crystal microbalance (QCM) biosensor to
      determine the kinetic constants of heparin and other sulfated polysaccharides
      binding to immobilized P-selectin. Binding kinetics of the derivatives were
      correlated with their inhibitory capacity in a P-selectin cell rolling assay.
      Three commercial heparins differ in cell rolling inhibition and display slightly
      different affinities (KD 1.21 x 10(-6) M to 5.86 x 10(-7) M). Inhibitory capacity
      appears to be mainly driven by a slow off-rate from the receptor (2.27 x 10(-3) s
      1 to 1.23 x 10(-3) s-1). To correlate the impact of binding kinetics on
      inhibitory capacity structurally, we analyzed six semisynthetic glucan sulfates.
      They display different degrees of sulfation (DS), which has a strong influence on
      inhibitory activity. Kinetic data illustrate that the inhibitory capacity
      correlates excellently with the off-rate of these polysaccharides (R = 0.99),
      while the association (on-rate) affects activity to a lesser extent. In general,
      the consideration of binding kinetics sheds new light on the mechanism of
      selectin inhibition. A much slower dissociation of the inhibitors from the
      receptor than the physiological ligands is key for inhibitory capacity.
      Structurally, highly charged compounds with a slow off-rate, such as heparin or
      glucan sulfates, appear as potent candidates for P-selectin inhibition.

PMID- 17458942
TI  - Electron spin exchange processes in strongly coupled spin triads.
AB  - The complexes of Cu2+ hexafluoroacetylacetonate with two pyrazol-substituted
      nitronyl nitroxides are the choice systems to study the spin dynamics of strongly
      exchange-coupled spin triads. The large values of exchange coupling (ca. 100 cm
      1) and high-resolution electron paramagnetic resonance (EPR) at Q- and W-bands
      (35 and 94 GHz) allowed us to observe and interpret specific characteristics of
      these systems. An electron spin exchange process has been found between different
      multiplets of the spin triad, which manifests itself as a significant shift of
      the EPR line position with temperature. We propose that the spin exchange process
      is caused by the modulation of exchange interaction between copper and nitroxides
      by lattice vibrations. The estimations of the rate of exchange process and model
      calculations essentially support the observed phenomena. The studied
      characteristics of strongly coupled spin triads explain previously obtained
      results, agree with literature, and should be accounted for in future
      investigations of similar spin systems.

PMID- 17458943
TI  - Ab initio study on the oxidation of NCN by O (3P): prediction of the total rate
      constant and product branching ratios.
AB  - The reaction of NCN with O is relevant to the formation of prompt NO according to
      the new mechanism, CH+N2-->cyclic-C(H)NN- -->HNCN-->H+NCN. The reaction has been
      investigated by ab initio molecular orbital and transition state theory
      calculations. The mechanisms for formation of possible product channels involved
      in the singlet and triplet potential energy surfaces have been predicted at the
      highest level of the modified GAUSSIAN-2 (G2M) method, G2M (CC1). The barrierless
      association/dissociation processes on the singlet surface were also examined with
      the third-order Rayleigh-Schrodinger perturbation (CASPT3) and the multireference
      configuration interaction methods including Davidson's correction for higher
      excitations (MRCI+Q) at the CASPT3(6,6)/6-311+G(3df)//UB3LYP/6-311G(d) and
      MRCI+Q(6,6)/6-311+G(3df)//UB3LYP/6-311G(d) levels. The rate constants for the low
      energy channels producing CO+N2, CN+NO, and N(4S)+NCO have been calculated in the
      temperature range of 200-3000 K. The results show that the formation of CN+NO is
      dominant and its branching ratio is over 99% in the whole temperature range; no
      pressure dependence was noted at pressures below 100 atm. The total rate constant
      can be expressed by: kt=4.23x10(-11) T0.15 exp(17/T) cm3 molecule(-1) s(-1).

PMID- 17458944
TI  - NMR study of methane + ethane structure I hydrate decomposition.
AB  - The thermally activated decomposition of methane + ethane structure I hydrate was
      studied with use of 13C magic-angle spinning (MAS) NMR as a function of
      composition and temperature. The observed higher decomposition rate of large sI
      cages initially filled with ethane gas can be described in terms of a model where
      a distribution of sI unit cells exists such that a particular unit cell contains
      zero, one, or two methane molecules in the unit cell; this distribution of unit
      cells is combined to form the observed equilibrium composition. In this model,
      unit cells with zero methane molecules are the least stable and decompose more
      rapidly than those populated with one or two methane molecules leading to the
      observed overall faster decomposition rate of the large cages containing ethane
      molecules.

PMID- 17458941
TI  - Bioflavonoids as poisons of human topoisomerase II alpha and II beta.
AB  - Bioflavonoids are human dietary components that have been linked to the
      prevention of cancer in adults and the generation of specific types of leukemia
      in infants. While these compounds have a broad range of cellular activities, many
      of their genotoxic effects have been attributed to their actions as topoisomerase
      II poisons. However, the activities of bioflavonoids against the individual
      isoforms of human topoisomerase II have not been analyzed. Therefore, we
      characterized the activity and mechanism of action of three major classes of
      bioflavonoids, flavones, flavonols, and isoflavones, against human topoisomerase
      IIalpha and IIbeta. Genistein was the most active bioflavonoid tested and
      stimulated enzyme-mediated DNA cleavage approximately 10-fold. Generally,
      compounds were more active against topoisomerase IIbeta. DNA cleavage with both
      enzyme isoforms required a 5-OH and a 4'-OH and was enhanced by the presence of
      additional hydroxyl groups on the pendant ring. Competition DNA cleavage and
      topoisomerase II binding studies indicate that the 5-OH group plays an important
      role in mediating genistein binding, while the 4'-OH moiety contributes primarily
      to bioflavonoid function. Bioflavonoids do not require redox cycling for activity
      and function primarily by inhibiting enzyme-mediated DNA ligation. Mutagenesis
      studies suggest that the TOPRIM region of topoisomerase II plays a role in
      genistein binding. Finally, flavones, flavonols, and isoflavones with activity
      against purified topoisomerase IIalpha and IIbeta enhanced DNA cleavage by both
      isoforms in human CEM leukemia cells. These data support the hypothesis that
      bioflavonoids function as topoisomerase II poisons in humans and provide a
      framework for further analysis of these important dietary components.

PMID- 17458945
TI  - Vibrational levels of Ar4: new odd-parity bosonic states.
AB  - Vibrational levels of Ar4 are computed using the Lanczos algorithm and a large
      basis set. We find both even- and odd-parity states with wave functions that are
      invariant with respect to permutations of the Ar atoms. The odd-parity bosonic
      levels have not been computed previously. The even-parity levels are close to
      those obtained using the correlation-function Monte Carlo method (CFMC).

PMID- 17458946
TI  - Structure-based design, synthesis, and A-site rRNA cocrystal complexes of
      functionally novel aminoglycoside antibiotics: C2" ether analogues of
      paromomycin.
AB  - A series of 2"-O-substituted ether analogues of paromomycin were prepared based
      on new site-selective functionalizations. X-ray cocrystal complexes of several
      such analogues revealed a new mode of binding in the A-site rRNA, whereby rings I
      and II adopted the familiar orientation and position previously observed with
      paromomycin, but rings III and IV were oriented differently. With few exceptions,
      all of the new analogues showed potent inhibitory activity equal or better than
      paromomycin against a sensitive strain of S. aureus. Single digit microM MIC
      values were obtained against E. coli, with some of the ether appendages
      containing polar or basic end groups. Two analogues showed excellent survival
      rate in a mouse septicemia protection assay. Preliminary histopathological
      analysis of the kidney showed no overt signs of toxicity, while controls with
      neomycin and kanamycin were toxic at lower doses.

PMID- 17458947
TI  - De novo parallel design, synthesis and evaluation of inhibitors against the
      reverse transcriptase of human immunodeficiency virus type-1 and drug-resistant
      variants.
AB  - We used molecular modeling to design de novo broad-range inhibitors against wild
      type and drug-resistant variants of the reverse transcriptase (RT) of human
      immunodeficiency virus type-1 (HIV-1). First, we screened for small fragments
      that would interact with each one of four RT structures (one wild type and three
      mutants). Then, these fragments were linked to build a scaffold molecule. Out of
      27 different compounds that were synthesized, four inhibited the DNA polymerase
      activity of RT with IC50 values below 10 microM. Compound 5f inhibited RT with an
      IC50 value of about 3.5 microM, while inhibiting drug-resistant RT variants more
      efficiently than the clinically used drug, nevirapine (11-cyclopropyl-5,11
      dihydro-4-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one). 5f also
      inhibited the RT ribonuclease H activity with an IC50 of 20 microM and therefore,
      unlike nevirapine, targets both RT activities. Accordingly, 5f can serve as lead
      for developing novel inhibitors against RT that may be used to suppress HIV-1
      growth.

PMID- 17458948
TI  - Synthesis and characterization of constrained peptidomimetic dipeptidyl peptidase
      IV inhibitors: amino-lactam boroalanines.
AB  - We describe here the epimerization-free synthesis and characterization of a new
      class of conformationally constrained lactam aminoboronic acid inhibitors of
      dipeptidyl peptidase IV (DPP IV; E.C. 3.4.14.5). These compounds have the
      advantage that they cannot undergo the pH-dependent cyclization prevalent in most
      dipeptidyl boronic acids that attenuates their potency at physiological pH. For
      example, D-3-amino-1-[L-1-boronic-ethyl]-pyrrolidine-2-one (amino-D-lactam-L
      boroAla), one of the best lactam inhibitors of DPP IV, is several orders of
      magnitude less potent than L-Ala-L-boroPro, as measured by Ki values (2.3 nM vs
      30 pM, respectively). At physiological pH, however, it is actually more potent
      than L-Ala-L-boroPro, as measured by IC50 values (4.2 nM vs 1400 nM), owing to
      the absence of the potency-attenuating cyclization. In an interesting and at
      first sight surprising reversal of the relationship between stereochemistry and
      potency observed with the conformationally unrestrained Xaa-boroPro class of
      inhibitors, the L-L diastereomers of the lactams are orders of magnitude less
      effective than the D-L lactams. However, this interesting reversal and the
      unexpected potency of the D-L lactams as DPP IV inhibitors can be understood in
      structural terms, which is explained and discussed here.

PMID- 17458949
TI  - Synthesis, characterization and in vivo studies of Cu(II)-64-labeled cross
      bridged tetraazamacrocycle-amide complexes as models of peptide conjugate imaging
      agents.
AB  - Copper-64, a positron emitter suitable for positron emission tomography (PET),
      demonstrates improved in vivo clearance when chelated by the cross-bridged
      tetraazamacrocycle CB-TE2A compared to TETA. Good in vivo clearance was also
      observed for 64Cu-CB-TE2A conjugated to a peptide, which converts one
      coordinating carboxylate pendant arm to an amide. To better understand the in
      vivo stability of peptide- conjugated CB-TE2A, cross-bridged monoamides were
      synthesized. Crystal structures of natCu(II)-CB-TEAMA and natCu(II)-CB-PhTEAMA
      revealed hexadentate, distorted octahedral coordination geometry. In vivo
      biodistribution showed clearance of all 64Cu-radiolabeled cross-bridged
      monoamides from liver and bone marrow such that uptake at 24 h was <10% of uptake
      at 30 min. In contrast, >60% of 30 min uptake from 64Cu-TETA was retained in
      these tissues at 24 h. Clearance of 64Cu-cross-bridged monoamides from nontarget
      organs suggests good in vivo stability, thus supporting the use of CB-TE2A as a
      bifunctional chelator without modifications to the macrocycle backbone.

PMID- 17458951
TI  - Evaluation of Pseudomonas aeruginosa deacetylase LpxC inhibitory activity of dual
      PDE4-TNFalpha inhibitors: a multiscreening approach.
AB  - In this study, we have focused on the implication of a multiscreening approach in
      the evaluation of Pseudomonas aeruginosa deacetylase LpxC inhibitory activity of
      dual PDE4-TNFalpha inhibitors. A genetic function approximation (GFA) directed
      quantitative structure-activity relationship (QSAR) model was developed for LpxC
      inhibition on the basis of reported biological activity (Kline and Andersen, J.
      Med. Chem. 2002, 45, 3112-3129). Subsequently, reported PDE4-TNFalpha inhibitors
      (Klienman and Campbell, J. Med. Chem. 1998, 41, 266-270) were screened using the
      QSAR model. Whereby, the compounds were predicted to have equipotent activity
      with the most potent compound in reported LpxC inhibitor series. A docking
      analysis of these compounds carried out on the LpxC homology model corroborated
      the initial results. The compounds were then validated using surface electronic
      properties analysis and subjected to an adsorption, distribution, metabolism,
      excretion, and toxicity filter. Taken together, a multiscreening strategy was
      used to validate potential leads for LpxC inhibition.

PMID- 17458952
TI  - Chemometric approach in quantification of structural identity/similarity of
      proteins in biopharmaceuticals.
AB  - We present a chemometrics study in which we show the identity or degree of
      similarity of 3D protein structures of various G-CSF (Granulocyte Colony
      Stimulating Factor) isolates. The G-CSF isolates share the same amino acid
      sequence, but the preparation was carried out by somehow diverse technologies.
      The comparison of 3D structures was made on the basis of 2D NMR NOESY (Nuclear
      Overhauser Enhancement Spectroscopy) spectra of proteins. In searching for the
      most appropriate criteria to determine the identity or degree of similarity of
      selected spectral regions of different isolates, two methods for quantitative
      evaluation of identity/similarity were used. The first method compares all peaks
      in the two investigated protein spectral regions; the extent of peaks that
      overlap is determined. The second method includes spectral invariants originating
      from graph theory. The criteria of identity/similarity were calculated from
      graphs, derived from a collection of up to 200 peaks of investigated 2D NMR
      spectral region. The peaks were linked into a graph according to the sequential
      nearest neighborhoods. According to the first method all peaks were relevant,
      considering that spectral noise was previously removed; the largest similarity
      was found between the protein of a commercially available G-CSF drug and one of
      the three new isolates produced in the laboratory. The second method indicated
      that the pairwise similarity of the three new isolates is larger than the
      similarity of any of the new isolates with the commercially available drug. This
      is an expected result taking into account that the new isolates are produced by
      the same technology, while the commercial product has additives for long-term
      storage that could not be completely compensated. The proposed measure of
      similarity may help the developers of biosimilar products to optimize the
      controllable parameters of the production technology and eventually to argue the
      identity of the new isolate in comparison with the originator commercial product.

PMID- 17458953
TI  - Characterization of room-temperature ionic liquids by the Abraham model with
      cation-specific and anion-specific equation coefficients.
AB  - Gas-to-RTIL (room-temperature ionic liquid) partition coefficients have been
      compiled for 592 different solute-RTIL combinations. These partition coefficients
      were converted into water-to-RTIL partition coefficients using the corresponding
      gas-to-water partition coefficients. Both sets of partition coefficients were
      analyzed using the Abraham solvation parameter model with cation-specific and
      anion-specific equation coefficients. The derived equations correlated the
      experimental gas-to-RTIL and water-to-RTIL partition coefficient data to within
      0.10 and 0.14 log units, respectively. The 8 sets of calculated cation-specific
      equation coefficients and 4 sets of calculated anion-specific equation
      coefficients can be combined to yield expressions capable of predicting the
      partition coefficients of solutes in 32 different RTILs.

PMID- 17458954
TI  - Magnetic interactions in CuII-LnIII cyclic tetranuclear complexes: is it possible
      to explain the occurrence of SMM behavior in CuII-TbIII and CuII-DyIII complexes?
AB  - An extensive series of tetranuclear CuII2LnIII2 complexes [CuIILLnIII(hfac)2]2
      (with LnIII being all lanthanide(III) ions except for the radioactive PmIII) has
      been prepared in order to investigate the nature of the CuII-LnIII magnetic
      interactions and to try to answer the following question: What makes the
      CuII2TbIII2 and CuII2DyIII2 complexes single molecule magnets while the other
      complexes are not? All the complexes within this series possess a similar cyclic
      tetranuclear structure, in which the CuII and LnIII ions are arrayed alternately
      via bridges of ligand complex (CuIIL). Regular SQUID magnetometry measurements
      have been performed on the series. The temperature-dependent magnetic
      susceptibilities from 2 to 300 K and the field-dependent magnetizations from 0 to
      5 T at 2 K have been measured for the CuII2LnIII2 and NiII2LnIII2 complexes, with
      the NiII2LnIII2 complex containing diamagnetic NiII ions being used as a
      reference for the evaluation of the CuII-LnIII magnetic interactions. These
      measurements have revealed that the interactions between CuII and LnIII ions are
      very weakly antiferromagnetic if Ln=Ce, Nd, Sm, Yb, ferromagnetic if Ln=Gd, Tb,
      Dy, Ho, Er, Tm, and negligible if Ln=La, Eu, Pr, Lu. With the same goal of better
      understanding the evolution of the intramolecular magnetic interactions, X-ray
      magnetic circular dichroism (XMCD) has also been measured on CuII2TbIII2,
      CuII2DyIII2, and NiII2TbIII2 complexes, either at the L- and M-edges of the metal
      ions or at the K-edge of the N and O atoms. Last, the CuII2TbIII2 complex
      exhibiting SMM behavior has received a closer examination of its low temperature
      magnetic properties down to 0.1 K. These particular measurements have revealed
      the unusual very slow setting-up of a 3D order below 0.6 K.

PMID- 17458955
TI  - New functional model complexes of intradiol-cleaving catechol dioxygenases:
      properties and reactivity of CuII(L)(O2Ncat).
AB  - Complexes Cu(O2Ncat)(tbeda) (1) and Cu(O2Ncat)(tmeda) (2) (tbeda = N,N,N',N'
      tetrabenzylethylenediamine, tmeda=N,N,N',N'-tetramethylethylenenediamine,
      O2NcatH2=4-nitrocatechol) have been prepared by the reaction of copper(II)
      perchlorate with 4-nitrocatechol in the presence of triethylamine and the
      appropriate bidentate ligand. These compounds represent structural and functional
      model systems for the copper-containing catechol 1,2-dioxygenase. Both complexes
      have been structurally characterized by X-ray crystallography and by UV-vis, IR,
      and EPR spectroscopies. Upon protonation of 1 and 2 with perchloric acid, the
      bidentate coordination of O2Ncat could be reversible converted to the monodentate
      coordination of O2NcatH. The equilibrium constants were found to be 4200 and
      3500, respectively, by measuring the UV-vis spectra in DMF. Back-titration with
      morpholine proved the reversibility of both reactions. Kinetic data on the
      oxygenation of 1 and 2 revealed overall second-order rate equations with kinetic
      parameters: ktbeda=(4.63+/-0.23)x10(-2) mol-1 dm3 s-1, DeltaH=51+/-6 kJ mol-1,
      DeltaS=-137+/-16 J mol-1 K-1; ktmeda=(0.89+/-0.23) mol-1 dm3 s-1, DeltaH=85+/-7
      kJ mol-1, DeltaS=-57+/-19 J mol-1 K-1 at 365.16 K. Oxygenation of 1, 2, and
      [Cu(O2NcatH)(L)]ClO4 (L=tbeda, tmeda) in DMF solution at ambient conditions gives
      the corresponding intradiol ring-cleaved (2-nitro-muconato)copper(II) complexes.
      These data support the assumption that the reaction of the differently
      coordinated catecholate ligand with dioxygen shows only 1,2-dioxygenase activity.

PMID- 17458956
TI  - A heterometallic porous material for hydrogen adsorption.
AB  - Two kinds of heterometallic complexes, {[Sm2(L)6Co2][Co(H2O)6].3H2O}n (Sm-Co) and
      {[Sm2(L)6Zn3(H2O)6].1.5H2O}n (Sm-Zn) (H2L=oxydiacetic acid), were synthesized
      under hydrothermal conditions. In Sm-Co, each L chelates to one Sm3+ center and
      bonds to two Co2+ ions in an anti-anti configuration. Sm and Co atoms are arrayed
      alternatively and connected by O-C-O bridges to form a cubic octahedral cage as
      the secondary building unit. Consequently, topological NaCl nets with high
      symmetry in the cubic space group Fdc have been constructed. It is interesting to
      note that Sm-Co contains interesting 2-fold interpenetrating 3D hydrogen-bonding
      supramolecular networks while in Sm-Zn each L adopts a syn-syn configuration to
      link two Zn2+ ions. Carboxylate groups bridge adjacent Sm and Zn atoms to create
      two kinds of metallocycles, Sm2(COO)4Zn2 and Sm6(COO)12Zn6, to be further
      assembled into a highly ordered 3D nanotubular structure. Sm-Zn represents the
      largest porous material among the heterometallic coordination polymers and the
      first example in the investigation of hydrogen adsorption. Sm-Zn possesses
      hydrogen storage capacity of up to 1.19 wt % at 77 K and 0.54 wt % at 298 K,
      respectively.

PMID- 17458957
TI  - A novel asymmetric hydroarsination reaction promoted by a chiral organopalladium
      complex.
AB  - The dissymmetrical chiral bidentate (R)-(+)-1-(diphenylphosphino)-2
      (diphenylarsino)propane was prepared stereoselectively via the novel asymmetric
      hydroarsination reaction between diphenylarsine and diphenyl-1-propenyl-(E)
      phosphine using di-mu-chlorobis{(S)-1-[1-(dimethylamino)ethyl]-2-naphthalenyl
      C,N}dipalladium(II) as the chiral reaction promoter.

PMID- 17458958
TI  - Combination of lacunary polyoxometalates and high-nuclear transition metal
      clusters under hydrothermal conditions. 3. Structure and characterization of
      [Cu(enMe)2]2{[Cu(enMe)2(H2O)]2[Cu6(enMe)2(B-a-SiW9O34)2]}.4H2O.
AB  - A novel sandwich-type polyoxometalate incorporating a unique hybrid hexanuclear
      copper cluster, [Cu(enMe)2]2{[Cu(enMe)2(H2O)]2[Cu6(enMe)2(B-a-SiW9O34)2]}.4H2O
      (1, enMe=1,2-diaminopropane), has been hydrothermally synthesized and
      structurally characterized by the elemental analyses, IR spectroscopy, TG
      analysis, magnetic properties, and single-crystal X-ray diffraction analysis.
      Crystal data for 1: triclinic, P; a=12.5105(2), b=14.3710(2), c=17.2687(2) A;
      alpha=98.834(1), beta=110.744(1), gamma=104.711(1) degrees; V=2704.57(7) A3;
      rho=3.646 g/cm3; Z=1. X-ray crystallographic study shows that the molecular
      structure of 1 contains 10 copper ions: Six of them form an unprecedented
      inorganic-organic hybrid Cu6 cluster via edge-sharing combination of two CuO6
      octahedra, two CuO5, and two CuO3N2 square pyramids and are encapsulated between
      two {B-a-SiW9O34} units. Two of them form two [Cu(enMe)2(H2O)]2+ complexes and
      further attach to the two {B-a-SiW9O34} units via two Cu-O=W bridges, acting as a
      decorated role. The remaining two form isolated [Cu(enMe)2]2+ complexes playing
      roles of charge-compensation and space-fillers. Magnetization measurement reveals
      that the hexanuclear copper cluster exhibits overall ferromagnetic interactions.

PMID- 17458959
TI  - 13-tungstoborate stabilized by an organostannoxane hexamer.
AB  - The novel dimethyltin-containing polyanion [{(CH3)2Sn}6(OH)2O2(H2BW13O46)2]12-
      (1) is composed of two [H2BW13O46]9- clusters linked by an unprecedented planar,
      hexameric [{(CH3)2Sn}6(OH)2O2]8+ organostannoxane moiety, representing the first
      X-ray structural characterization of a molecular hybrid organic-inorganic
      tungstoborate and of the elusive [HnBW13O46](11-n)- species.

PMID- 17458960
TI  - Alcohol addition to acetonitrile activated by the [Re6(mu3-Se)8]2+ cluster core.
AB  - The addition of methanol and ethanol to the previously reported cluster solvates
      [Re6(mu3-Se)8(PEt3)5(MeCN)](SbF6)2 and trans-[Re6(mu3-Se)8(PEt3)4(CH3CN)2][SbF6]2
      afforded three cluster complexes with imino ester ligands: {Re6(mu3
      Se)8(PEt3)5[HN=C(OCH3)(CH3)]}(SbF6)2, {Re6(mu3
      Se)8(PEt3)5[HN=C(OCH2CH3)(CH3)]}{SbF6}2, and trans-{Re6(mu3
      Se)8(PEt3)4[HN=C(OCH3)(CH3)]2}{SbF6}2. In all cases, predominant formation of the
      Z isomers was observed.

PMID- 17458961
TI  - Rapid screening of gold catalysts by chemiluminescence-based array imaging.

PMID- 17458962
TI  - Effect of the surface curvature on the secondary structure of peptides adsorbed
      on nanoparticles.

PMID- 17458963
TI  - Spin switching via targeted structural distortion.
AB  - The deliberate "stepwise" structural distortion of the [MnIII6O2(sao)6(O2CR)2L4]
      (S = 4, Ueff = 28 K) family of SMMs (where sao2- is the dianion of
      salicylaldoxime or 2-hydroxybenzaldeyhyde oxime and L = MeOH, EtOH) via the use
      of derivatized oxime ligands and bulky carboxylates leads to a family of single
      molecule magnets with larger spin ground states and enhanced blocking
      temperatures. Replacing sao2- and HCO2- in the molecule
      [MnIII6O2(sao)6(O2CH)2(MeOH)4] (1), with Et-sao2- (Et-saoH2 = 2
      hydroxypropiophenone oxime) and Me3CCO2- (pivalate), produces the complex
      [MnIII6O2(Et-sao)6(O2CCMe3)2(EtOH)5] (2) that displays an S = 7 ground state with
      Ueff = 30 K. Replacing Me3CCO2- with PhCO2- produces the complex [MnIII6O2(Et
      sao)6(O2CPh)2(EtOH)4(H2O)2] (3) that displays an S = 12 ground state with Ueff =
      53 K. The ligand substitution invokes a subtle structural distortion to the core
      of the molecule evidenced by an increased "twisting" of the oxime moiety (Mn-N-O
      Mn) and a change in carboxylate ligation, which, in turn, invokes a dramatic
      change in the observed magnetic properties by switching weak antiferromagnetic
      exchange to weak ferromagnetic exchange.

PMID- 17458964
TI  - Isotopically discriminated NMR spectroscopy: a tool for investigating complex
      protein interactions in vitro.
AB  - A new NMR approach is presented for observing in vitro multicomponent protein
      protein-ligand(s) interactions, which should help to understand how cellular
      networks of protein interactions operate on a molecular level and how they can be
      controlled with drugs. The method uniquely allows at least two polypeptide
      components of the mixture to be simultaneously closely monitored in a single
      sample, without increased signal overlap, and can be used to study complex (e.g.,
      sequential, competitive, cooperative, allosteric, induced, etc.) binding events,
      witnessed by two polypeptides independently. One polypeptide is uniformly labeled
      with 15N and another with 15N and 13C. The 1H-15N correlation spectra are
      recorded for each of these molecules separately, discriminated on the basis of
      the type of 13C'/12C' atom attached to the amide group nitrogen. Any changes to
      the state of the two differently isotopically labeled molecules will be reported
      individually by fingerprint signals from amide groups, e.g., as unlabeled ligands
      are added. To our knowledge, no other technique currently exists which can
      monitor complex binding events in similar detail. The proposed method can be
      combined easily with traditional protein NMR techniques and incorporated in a
      variety of applications.

PMID- 17458965
TI  - High-sensitivity humidity sensor based on a single SnO(2) nanowire.

PMID- 17458966
TI  - Rapid removal of D(5)(h) isomer using the "stir and filter approach" and
      isolation of large quantities of isomerically pure Sc(3)N@C(80) metallic nitride
      fullerenes.

PMID- 17458967
TI  - DNA-mediated electrochemistry of disulfides on graphite.

PMID- 17458968
TI  - Total synthesis and structure revision of the marine metabolite palmerolide A.

PMID- 17458969
TI  - Enrichment of single chirality carbon nanotubes.

PMID- 17458970
TI  - Remarkably facile and reversible Ru-C(sp3) bond cleavage to give a reactive 16
      electron Cp*Ru(kappa2-P,carbene) zwitterion.

PMID- 17458971
TI  - Low-temperature formation of nitrous oxide from dinitrogen, mediated by supported
      tungsten nanoclusters.

PMID- 17458972
TI  - Pyrene-benzoylthiophene exciplexes as selective catalysts for the [2+2]
      cycloaddition between cyclohexadiene and styrenes.
AB  - Efficient intramolecular fluorescence quenching in pyrene-benzoylthiophene
      systems leads to formation of exciplexes. These species interact with 1,3
      cyclohexadiene (or styrenes), leading to reactive excited triplexes. The overall
      process affords [2+2] cross-cycloadducts with an average yield of 57%.

PMID- 17458973
TI  - Rh-catalyzed [4 + 2] carbocyclization of vinylarylaldehydes with alkenes and
      alkynes leading to substituted tetralones and 1-naphthols.
AB  - Regio-, diastereo-, and enantioselective intermolecular [4 + 2] carbocyclizations
      of vinylarylaldehydes with alkenes and alkynes leading to substituted tetralones
      and 1-naphthols have been developed by using a cationic rhodium(I)/dppb or dppp
      complex as a catalyst.

PMID- 17458974
TI  - Synthesis of tetracene sulfoxide and tetracene sulfone via a cascade cyclization
      reaction.
AB  - A facile synthesis of tetracene sulfoxides and sulfones based on o-diallene
      annulation initiated cascade cyclization was developed. The photophysical
      behavior of these tetracene derivatives can be generally rationalized by the
      presence of electron-withdrawing sulfoxides and sulfones at the 5-position.

PMID- 17458975
TI  - Desymmetrization of 1,4-cyclohexadienyltriisopropoxysilane using copper
      catalysis.
AB  - The first catalytic desymmetrization in the field of allylsilane chemistry is
      presented. Desymmetrization of cyclohexadienyltriisopropoxysilane is achieved
      using coppper catalysis. High diastereo- and enantioselectivities are obtained,
      and the product dienes are highly valuable building blocks for natural product
      synthesis.

PMID- 17458976
TI  - Highly stereoselective prins cyclization of (Z)- and (E)-gamma-brominated
      homoallylic alcohols to 2,4,5,6-tetrasubstituted tetrahydropyrans.
AB  - An efficient method has been developed to construct 2,6-cis-4,5-dibromo
      tetrasubstituted tetrahydropyran (THP) rings with well-controlled stereochemistry
      in moderate to high yields.

PMID- 17458977
TI  - Cationic Rh(I)/modified-BINAP-catalyzed reactions of carbonyl compounds with 1,6
      diynes leading to dienones and ortho-functionalized aryl ketones.
AB  - We have determined that a cationic rhodium(I)/H8-BINAP complex catalyzes a [2 + 2
      + 2] cycloaddition of both activated and unactivated carbonyl compounds with 1,6
      diynes leading to dienones in high yields. On the other hand, unactivated aryl
      ketones react with 1,6-diynes in the presence of a cationic rhodium(I)/Segphos
      complex to give ortho-functionalized aryl ketones in high yields.

PMID- 17458978
TI  - Prediction of Penicillium expansum spoilage and patulin concentration in apples
      used for apple juice production by electronic nose analysis.
AB  - Classification models for Penicillium expansum spoilage of apples and prediction
      models for patulin concentration in apples usable for apple juice production were
      made on the basis of electronic nose (e-nose) analysis correlated to HPLC
      quantification of patulin. A total of 15 Golden Delicious and 4 Jonagold apples
      were surface sterilized and divided into three groups per variety. The Golden
      Delicious group consisted of five apples each. Group 1 was untreated control,
      group 2 was surface inoculated with P. expansum, and group 3 was inoculated in
      the core with P. expansum. The apples were incubated at 25 degrees C for 10 days.
      E-nose analysis was performed daily. At day 10 the Golden Delicious apples were
      individually processed for apple juice production. During apple juice production
      the mash and juice were analyzed by e-nose, and samples were taken for patulin
      analysis by HPLC. The volatile metabolite profile was obtained by collection of
      volatile metabolites, on tubes containing Tenax TA, overnight between the 9th and
      10th days of incubation and subsequent analysis of the collected compounds by GC
      MS. Prediction models using partial least-squares, with high correlation, for
      prediction of patulin concentration in shredded apples as well as apple juice
      were successfully created. It was also shown that it is possible to classify P.
      expansum spoilage in apples correctly on the basis of soft independent modeling
      of class analogy classification of e-nose analysis data. To the authors'
      knowledge this is the first report of a regression model between e-nose data and
      mycotoxin content in which actual concentrations are reported. This implies that
      it is possible to predict mycotoxin production and concentration by e-nose
      analysis.

PMID- 17458979
TI  - Oligomeric procyanidins in apple polyphenol are main active components for
      inhibition of pancreatic lipase and triglyceride absorption.
AB  - Inhibitory effects of apple polyphenol extract (AP) and procyanidin contained in
      AP on in vitro pancreatic lipase activity and in vivo triglyceride absorption in
      mice and humans were examined. AP and procyanidin considerably inhibited in vitro
      pancreatic lipase activity. However, polyphenols, except for procyanidin, in AP
      (i.e., catechins, chalcones, and phenol carboxylic acids) showed weak inhibitory
      activities on pancreatic lipase. Procyanidins separated by normal-phase
      chromatography according to the degree of polymerization were also examined.
      Inhibitory effects of procyanidins increased according to the degree of
      polymerization from dimer to pentamer. On the other hand, pentamer or greater
      procyanidins showed maximal inhibitory effects on pancreatic lipase. These
      results suggested that with respect to in vitro pancreatic lipase inhibition, the
      degree of polymerization was an important factor and oligomeric procyanidin
      mainly contributed. Next, we performed a triglyceride tolerance test in mice and
      humans. Simultaneous ingestion of AP and triglyceride significantly inhibited an
      increase of plasma triglyceride levels in both models. These results suggested
      that the oligomeric procyanidins contained in AP inhibited triglyceride
      absorption by inhibiting pancreatic lipase activity in mice and humans.

PMID- 17458980
TI  - Development of immunosensors using carbon nanotubes.
AB  - With increasing reports on bioterrorism, avian flu, and other bio-threats, rapid
      and real time detection methods are highly warranted. Studies on developing
      highly sensitive immunosensors aiming at the early detection and clinical
      diagnoses of various diseases including cancer are undertaken all over the globe.
      Carbon nanotubes (CNTs) have been widely discussed as materials with enormous
      potential for a wide range of in vivo and in vitro bioapplications, ranging from
      drug delivery to highly sensitive biosensors, owing to their superior electronic
      and mechanical properties along with nanoscale dimensions. Though a lot of
      attention has been drawn toward carbon nanotubes for the past 15 years in
      academia and to a certain extent in industry, CNT-based immunosensors and other
      applications are still in the nascent stage, and there are many challenges to be
      overcome for the successful commercialization of the concepts. This article
      highlights on the recent developments and the possible impacts of carbon nanotube
      based immunosensors.

PMID- 17458981
TI  - Polybenzoxazine as a mold-release agent for nanoimprint lithography.
AB  - One of the most important tasks remaining to be resolved in nanoimprint
      lithography is the elimination of the resist sticking to the mold during
      demolding. Previously, the main approach was to apply a thin layer of fluorinated
      alkyl silane mold-release agent on the surface on the mold; however, this
      involves complicated steps and high costs. The low surface free energy material
      polybenzoxazine provides an efficient mold-release agent for silicon molds that
      is easier to process, costs less, and has no side reactions.

PMID- 17458982
TI  - In situ surface-enhanced infrared absorption spectroscopy for the analysis of the
      adsorption and desorption process of Au nanoparticles on the SiO2/Si surface.
AB  - The adsorption and desorption of Au nanoparticles (AuNP) in colloidal D2O
      suspension on the (3-aminopropyl)triethoxysilane treated SiO2/Si surface was
      investigated by in situ attenuated total reflection surface enhanced infrared
      absorption (ATR-SEIRA) spectroscopy with a liquid flow cell. With increasing
      surface density of AuNP, the absorption of the vibrational modes of D2O and of
      the citrate molecules covering the AuNP increases due to SEIRA. Repulsive
      electrostatic Coulomb forces between the AuNP lead to the saturation of the AuNP
      surface density at submonolayer coverage. We show that the adsorption kinetics
      can be investigated by monitoring in situ the molecular vibrational modes of D2O
      and the citrate molecules. Furthermore, we clarify that the adsorption process
      can be described very well by a diffusion-limited first-order Langmuir kinetics
      model. When exposing a saturated AuNP submonolayer to 2-aminoethanethiol
      (AET)/D2O solution, the AuNP are removed from the surface and the IR absorption
      of the D2O vibrational modes become weaker again. Taking into account the time
      dependencies of the OD and the CH peaks, we propose a microscopic model where the
      AET molecules quickly adsorb on the AuNP by replacing most of the precovering
      citrate molecules exposed to the AET solution. As this takes place, the AuNP
      agglomerate-as we could detect with scanning electron microscopy-and are finally
      removed from the surface.

PMID- 17458983
TI  - Characterization of self-assembled monolayers of oligo(phenyleneethynylene)
      derivatives of varying shapes on gold: effect of laterally extended pi-systems.
AB  - Fully conjugated organic molecules, such as the oligo(phenyleneethynylene) (OPE)
      systems, are of growing interest within the field of molecular electronics, as is
      the self-assembly of well-defined molecular thin films with predefined functions.
      The structure and function of such films are intimately related and governed by
      the structures of their molecular constituents, through the intermolecular
      interactions and the interactions between the molecules and the substrate, onto
      which the film is assembled. Here we report on the synthesis of a series of three
      OPE derivatives, with the general structure phenylethynylene-aryl
      ethynylenephenylene-headgroup, and the structural investigation of the self
      assembled monolayers (SAMs) formed from them on Au(111) surfaces. The SAMs were
      characterized by infrared reflection-absorption spectroscopy, spectroscopic
      ellipsometry, high-resolution X-ray photoemission spectroscopy, and near-edge X
      ray absorption fine structure spectroscopy. The effective thickness of the SAMs
      was observed to decrease as the pi-system of the aryl moiety of the OPE adsorbate
      was extended perpendicular to its molecular long axis. Changing the aryl moiety
      from benzene to naphthalene to anthracene resulted in lower molecular surface
      densities and larger molecular inclination. The average tilt angles for the
      benzene, naphthalene, and anthracene SAMs were found to be about 30 degrees , 40
      degrees , and 42 degrees from the surface normal, respectively. For the largest
      adsorbate, the anthracene derivative, there is spectroscopic evidence suggesting
      the existence of nonequivalent binding sites. The differences observed between
      the SAMs are rationalized in terms of the shape of the adsorbates and the
      strength of the pi-pi interactions between them.

PMID- 17458984
TI  - Molecular weight segregation on surfaces of polyethylene blended films as
      estimated from nanoscratch tests using scanning probe microscopy.
AB  - Nanoscratch tests using scanning probe microscopy (SPM) were performed on films
      prepared from two polyethylene (PE) materials polymerized by using a metallocene
      catalyst system with different molecular weights (MWs). Blended samples were
      prepared by dissolving both PE materials at various ratios in hot p-xylene. The
      pure and blended samples were compression molded into films at 180 degrees C for
      different holding times in the molten state. The results of SPM nanoscratch tests
      with an applied load of 30 nN indicated that the lower-MW surface could be easily
      plowed with wear debris but the higher-MW surface was less deformed. However, the
      deformation pattern of the blended film surface was similar to that of the lower
      MW surface. These results suggest that MW segregation occurs during holding in
      the molten state as lower-MW components rise to the film surface.

PMID- 17458985
TI  - Preparation of petaloid microspheres of basic magnesium carbonate.
AB  - The synthesis of basic magnesium carbonate was examined under ultrasonic
      irradiation and was performed by the soda ash method using magnesium sulfate and
      sodium carbonate as starting materials. The particulate product was evaluated
      using SEM observations. Ultrasonic irradiation in the preparation of basic
      magnesium carbonate was found to give fine petaloid microspheres of about 3 mum
      in primary particle size.

PMID- 17458986
TI  - Self-organization of polymerizable bolaamphiphiles bearing diacetylene mesogenic
      group.
AB  - We report herein the synthesis of a series of polymerizable bolaamphiphiles
      containing a diacetylene group and mesogenic unit and their self-organization
      behaviors in bulk and at interface. The polymerizable bolaamphiphiles are noted
      as DPDA-n, where n refers to the spacer length of alkyl chain. DPDA-10 with
      suitable spacer length can self-organize into stable cylindrical micellar
      nanostructures, and these nanostructures have preferred orientation regionally
      when adsorbed at the mica/water interface. It is confirmed that the micellar
      nanostructure of DPDA-10 can be polymerized both in the bulk solution and in the
      film by UV irradiation. The emission property of DPDA-10 after UV irradiation has
      been significantly enhanced in comparison to that before polymerization, which
      may be due to the extension of the conjugated system arising from the
      transformation of the diacetylene group into polydiacetylene upon polymerization.
      In addition, the self-organization of DPDA-n is dependent on the spacer length.
      DPDA-7 with a short spacer length forms an irregular flat sheet structure with
      many defects; DPDA-15 with a long spacer length forms rodlike micellar
      structures. Thus, this work may provide a new approach for designing and
      fabricating organic functional nanostructured materials.

PMID- 17458987
TI  - Grid pattern of nanothick microgel network.
AB  - A novel grid pattern of two kinds of nanothick microgels was developed by
      alternate patterning using photolithography. At first, 100-microm-wide nanothick
      PAAm microgel stripes were grafted on a polystyrene surface by UV irradiation of
      the photoreactive azidobenzoyl-derivatized polyallylamine-coated surface through
      a photomask with 100-microm-wide stripes. Then, a second set of 100-microm-wide
      nanothick PAAc microgel stripes were grafted across the PAAm-grated polystyrene
      surface by UV irradiation of the photoreactive azidophenyl-derivatized
      poly(acrylic acid)-coated surface through a photomask placed perpendicularly to
      the first set of PAAm microgel stripes. The PAAc microgel stripe pattern was
      formed over the PAAm microgel stripe pattern. The cross angle of the two microgel
      stripes could be controlled by adjusting the position of the photomask when the
      second microgel pattern was prepared. Swelling and shrinking of the microgels
      were investigated by scanning probe microscopy (SPM) in an aqueous solution. SPM
      observation indicated that the thickness of the gel network was 100 to 500 nm.
      The regions containing PAAm, PAAc, and the PAAc-PAAm overlapping microgels showed
      different swelling and shrinking properties when the pH was changed. The PAAm
      microgel swelled at low pH and shrank at high pH whereas the PAAc microgel
      swelled at high pH and shrank at low pH. However, the PAAc-PAAm overlapping
      microgel did not change as significantly as did the two microgels, indicating
      that the swelling and shrinking of the two gels was partially offset. The pH
      induced structural change was repeatedly reversible. The novel grid pattern of
      nanothick microgels will find applications in various fields such as smart
      actuators, artificial muscles, sensors, and drug delivery systems as well as in
      tissue engineering and so forth.

PMID- 17458988
TI  - Proteomics-based method for the assessment of marine pollution using liquid
      chromatography coupled with two-dimensional electrophoresis.
AB  - Using a proteomic approach, we have developed a new method for the assessment of
      marine pollution that generates highly reproducible protein expression patterns
      and it is simple and scalable. The protocol is based on applying liquid
      chromatography (LC) coupled with two-dimensional electrophoresis (2-DE) to
      analyze changes in the protein expression pattern after exposure to marine
      pollution. The digestive gland of the sentinel "blue mussel" (Mytilus edulis) was
      batch-processed through a simple cell fractionation followed by ion-exchange
      chromatography and 2-DE. The selection of ligands, elution method, and small
      volume design was carefully considered to define a protocol that could be mainly
      robotized. A pilot study with samples collected from different Gothenburg harbor
      areas indicated that the clean area could be distinguished from the polluted ones
      based on a protein expression pattern (PES) composed of 13 proteins. Principal
      component analysis (PCA) and hierarchical clustering confirmed that the PES was
      sufficient to discriminate polluted and unpolluted areas and to provide a spatial
      gradient from the polluted source. Several proteins from the PES were identified
      by electrospray ionization tandem mass spectrometry (ESI-MS/MS), and they are
      involved in beta-oxidation, amino acid metabolism, detoxification, protein
      degradation, organelle biogenesis, and protein folding. In the near future, this
      methodology could show potential advantages to assess marine pollution and could
      become a stable platform to elucidate ecotoxicological questions.

PMID- 17458989
TI  - Interfacial water structure controls protein conformation.
AB  - A phenomenological theory of salt-induced Hofmeister phenomena is presented,
      based on a relation between protein solubility in salt solutions and protein
      water interfacial tension. As a generalization of previous treatments, it implies
      that both kosmotropic salting out and chaotropic salting in are manifested via
      salt-induced changes of the hydrophobic/hydrophilic properties of protein-water
      interfaces. The theory is applied to describe the salt-dependent free energy
      profiles of proteins as a function of their water-exposed surface area. On this
      basis, three classes of protein conformations have been distinguished, and their
      existence experimentally demonstrated using the examples of bacteriorhodopsin and
      myoglobin. The experimental results support the ability of the new formalism to
      account for the diverse manifestations of salt effects on protein conformation,
      dynamics, and stability, and to resolve the puzzle of chaotropes stabilizing
      certain proteins (and other anomalies). It is also shown that the relation
      between interfacial tension and protein structural stability is straightforwardly
      linked to protein conformational fluctuations, providing a keystone for the
      microscopic interpretation of Hofmeister effects. Implications of the results
      concerning the use of Hofmeister effects in the experimental study of protein
      function are discussed.

PMID- 17458990
TI  - NMR solvent shifts of adenine in aqueous solution from hybrid QM/MM molecular
      dynamics simulations.
AB  - We present first principles calculations of the NMR solvent shift of adenine in
      aqueous solution. The calculations are based on snapshots sampled from a
      molecular dynamics simulation, which were obtained via a hybrid quantum
      mechanical/mechanical modeling approach, using an all-atom force field (TIP3P).
      We find that the solvation via the strongly fluctuating hydrogen bond network of
      water leads to nontrivial changes in the NMR spectra of the solutes regarding the
      ordering of the resonance lines. Although there are still sizable deviations from
      experiment, the overall agreement is satisfactory for the 1H and 15N NMR shifts.
      Our work is another step toward a realistic first-principles prediction of NMR
      chemical shifts in complex chemical environments.

PMID- 17458991
TI  - Search for more stable C58X18 isomers: stabilities and electronic properties of
      seven-membered ring C58X18 fullerene derivatives (X = H, F, and Cl).
AB  - Stimulated by recent preparation and characterization of the first C58F18
      fullerene derivative, with a heptagon in the framework (Science, 2005, 309, 278),
      we have performed systematic density functional studies on the stabilities and
      electronic properties of two different structures C58X18 (A) and C58X18 (B),
      where X = H, F, and Cl. The large energy gaps between the highest occupied
      molecular orbitals and the lowest unoccupied molecular orbitals (between 2.64 and
      3.45 eV) and the aromatic character (with nucleus independent chemical shifts
      from -10.0 to -13.9 ppm) of C58X18 (A) and C58X18 (B) indicate that they possess
      high stabilities. Further investigations show that the heats of formation of
      C58X18 fullerene derivatives are highly exothermic, suggesting that adding nine
      X2's releases much of the strain of pure C58 fullerene and leads to stabilities
      of the derivatives. Lower in energy and stronger in aromatic character than
      C58F18 (B), which has been experimentally characterized, C58F18 (A) should also
      be isolated. In addition, C58F18 and C58Cl18 are predicted to possess large
      electron affinities, especially for C58F18 (B) and C58Cl18 (B) with values of
      3.00 and 3.06 eV, respectively, even larger than that (2.50 eV) of C60F18. Hence,
      C58F18 and C58Cl18 can serve as good electron-acceptors with possible
      photonic/photovoltaic application. The IR spectra of C58X18 are simulated to
      facilitate identification of different isomers experimentally. In addition, the
      electronic spectra and second-order hyperpolarizabilities of C58X18 are predicted
      by ZINDO and sum-over-states model. With the addition of 9X2, both the static and
      frequency-dependent second-order hyperopolarizabilities of C58X18 greatly
      decrease compared to those of C58.

PMID- 17458992
TI  - Ab initio folding of albumin binding domain from all-atom molecular dynamics
      simulation.
AB  - Ab initio folding with all-atom model remains to be a difficult task even for
      small proteins. In this report, we conducted an accumulated 24 mus simulations on
      the wild type and two mutants of albumin binding domain (ABD) using the AMBER
      FF03 all-atom force field and a generalized-Born solvation model. Folding events
      have been observed in multiple trajectories, and the best folded structures
      achieved root-mean-square deviation (RMSD) of 2.0 A. The folding of this three
      helix bundle protein followed a diffusion-collision process, where substantial
      formation of the individual helices was critical and preceded the global packing.
      Owing to the difference in the intrinsic helicity, helix I formed faster than the
      other two helices. The order of the formation of helices II and III varied in
      different trajectories, indicating heterogeneity of the folding process. The
      slightly shifted boundaries of the helical segments had direct impact on the
      global packing, suggesting room for improvement on the simulation force field and
      solvation model.

PMID- 17458993
TI  - Conformations of proline analogues having double bonds in the ring.
AB  - The intrinsic conformational preferences of proline analogues having double bonds
      between carbon atoms in their rings have been investigated using quantum
      mechanical calculations at the B3LYP/6-31+G(d,p) level. For this purpose, the
      potential energy surface of the N-acety-N'-methylamide derivatives of three
      dehydroprolines (proline analogues unsaturated at alpha,beta; beta,gamma; and
      gamma,delta) and pyrrole (proline analogue with unsaturations at both alpha,beta
      and gamma,delta) have been explored, and the results are compared with those
      obtained for the derivative of the nonmodified proline. We found that the double
      bonds affect the ring puckering and the geometric internal parameters, even
      though the backbone conformation was influenced the most. Results indicate that
      the formation of double bonds between carbon atoms in the pyrrolidine ring should
      be considered as an effective procedure to restrict the conformational
      flexibility of prolines. Interestingly, we also found that the N-acetyl-N'
      methylamide derivative of pyrrole shows a high probability of having a cis
      peptide bond preceding the proline analogue.

PMID- 17458994
TI  - Hydrogen-abstracted adenine-thymine radicals with interesting transferable
      properties.
AB  - The formation of radicals on DNA bases through various pathways can lead to
      harmful structural alterations. Such processes are of interest for preventing
      alteration of healthy DNA and, conversely, to develop more refined methods for
      inhibiting the replication of unwanted mutagenic DNA. In the present work, we
      explore theoretically the energetic and structural properties of the nine
      possible neutral radicals formed via hydrogen abstraction from the adenine
      thymine base pair. The lowest energy radical is formed by loss of a hydrogen atom
      from the methyl group of thymine. The next lowest energy radicals, lying 8 and 9
      kcal mol-1 higher than the global minimum, are those in which hydrogens are
      removed from the two nitrogens that would join the base pair to 2-deoxyribose in
      double-stranded DNA. The other six radicals lie between 16 and 32 kcal mol-1
      higher in energy. Unlike the guanine-cytosine base pair, adenine-thymine (A-T)
      exhibits only minor structural changes upon hydrogen abstraction, with all A-T
      derived radicals maintaining planarity. Moreover, the energetic ordering for the
      radicals of the two isolated bases (adenine and thymine) is preserved upon
      formation of the base pair, though with a wider spread of energies. Even more
      significantly, the energetic interleaving of the (A-H)*-T and A-(T-H)* radicals
      is correctly predicted from the X-H bond dissociation energies of the isolated
      adenine and thymine. This suggests that the addition of the hydrogen-bonded
      complement base only marginally affects the bond energies.

PMID- 17458995
TI  - Amphiphilic block copolymer nanotubes and vesicles stabilized by
      photopolymerization.
AB  - We report on a new method to stabilize nanotube and vesicle structures created
      from amphiphilic diblock copolymers by means of photopolymerization. Cross
      linking with UV light exposure minimizes fluid disruption during stabilization.
      Additionally, the spatial control afforded by focusing or masking the initiating
      light source enables stabilization of distinct segments of individual
      nanostructures. This contribution demonstrates (1) that vesicles and nanotubes
      formed from poly(ethylene oxide)-block-polybutadiene are stabilized by exposure
      to UV light in the presence of a water-soluble photoinitiator and (2) that new
      nanotube geometries can be constructed by means of spot-curing, and (3) it
      reveals an application for photopolymerized nanotubes by showing electrophoresis
      of DNA through a UV-stabilized nanotube.

PMID- 17458996
TI  - Novel symmetric amphiphilic dendritic poly(L-lysine)-b-poly(L-lactide)-b
      dendritic poly(L-lysine) with high plasmid DNA binding affinity as a
      biodegradable gene carrier.
AB  - This study communicates the molecular design, preparation, and biological
      application of novel symmetric amphiphilic polycationic dendritic poly(L-lysine)
      b-poly(L-lactide)-b-dendritic poly(L-lysine) D2-LLA15-D2 bearing two two
      generation poly(L-lysine) PLL dendrons D2 and a central hydrophobic biodegradable
      poly(L-lactide) block LLA15. First, an amino-protected precursor of L1-OH was
      designed and synthesized and was further employed to prepare L1-LLA15 with an
      organic 4-(dimethylamino)-pyridine-mediated living-ring-opening polymerization of
      l-lactide. Subsequently, the hydroxy end-capped L1-LLA15 was coupled to
      synthesize a new triblock L1-LLA15-L1 with two one-generation amino-protected PLL
      dendrons L1. Furthermore, with a repeated trifluoroacetic-acid-mediated amino
      deprotection-protection cycle, new amphiphilic triblock D2-LLA15-D2 was
      successfully prepared. By means of NMR, mass spectrometry, and gel permeation
      chromatography, these synthetic precursors and final amphiphilic product were
      characterized to bear well-defined triblock structures. In addition, this
      synthesized amphiphilic triblock polycationic macromolecule was applied as a new
      polycationic plasmid DNA carrier, and its DNA binding affinity was examined via
      an agarose electrophoresis and a fluorescence titration assay along with two
      important references of hydrophilic dendritic D2-HEX-D2 and double-hydrophilic D2
      PEG-4K-D2 bearing the same two D2 dendrons; much enhanced DNA binding affinity
      was interestingly revealed for the new amphiphilic structural D2-LLA15-D2.
      Moreover, the assembled polyplex microparticles of plasmid DNA/polycationic
      carrier were further analyzed by dynamic light scattering and transmission
      electron microscopy, indicating their averaged nanoparticle size around 150-200
      nm. As for the cytotoxicity of the new D2-LLA15-D2, MTT assays were conducted
      with a human hepatocellular carcinoma cell line (SMMC-7721), indicating a very
      low cytotoxicity as compared with commercial linear PLL-23K and PEI-2K, and a
      DNase I degradation of the assembled polyplex particles was also done in the HBS
      buffer solution to evaluate their stabilities. Finally, employing the new
      amphiphilic D2-LLA15-D2 as gene carrier, in vitro gene transfection experiments
      were conducted with the SMMC-7721 cell line, indicating a transfection efficiency
      increase of at least 10 times higher than that of the naked plasmid DNA under a
      N/P charge ratio of 10. Therefore, these interesting results may provide a new
      possible way to construct efficient polycationic macromolecular gene carriers
      with low toxicity and less expensive low-generation PLL dendrons.

PMID- 17458997
TI  - A mild and efficient synthesis of 4-quinolones and quinolone heterocycles.
AB  - The cycloacylation of aniline derivatives to 4-quinolones in the presence of
      Eaton's reagent is described. This high-yielding methodology is applicable to a
      wide variety of functionalized anilines and requires milder conditions than those
      traditionally employed. This cyclization protocol is used to prepare a host of
      heterocycles and bis-quinolones and is characterized by relatively low reaction
      temperature and ease of product isolation.

PMID- 17458998
TI  - Enantioselective epoxidation of conjugated cis-enynes by chiral dioxirane.
AB  - This paper describes a highly chemo- and enantioselective epoxidation of
      conjugated cis-enynes using readily available glucose-derived ketone 2 as
      catalyst and Oxone as oxidant to form cis-propargyl epoxides in high ee's. The
      interaction between the alkyne group of the substrate and the oxazolidinone
      moiety of the ketone catalyst as well as the interactions between the
      substituents on enynes and the oxazolidinone moiety of the ketone catalyst are
      important for the stereodifferentiation.

PMID- 17458999
TI  - 1-Benzotriazol-1-yl-3,3,3-trifluoro-2-methoxy-2- phenylpropan-1-ones: Mosher-Bt
      reagents.
AB  - Benzotriazole derivatives of 3,3,3-trifluoro-2-methoxy-2-phenylpropionic acid
      react with water-soluble amino acids and peptides in an acetonitrile/water (2:1)
      mixture to give the corresponding amides in quantitative yield.

PMID- 17459000
TI  - Noel T. Keen--pioneer leader in molecular plant pathology.
AB  - Noel T. Keen (1940-2002) made pioneering contributions to molecular plant
      pathology during a period when the study of disease mechanisms was transformed by
      the new tools of molecular genetics. His primary contributions involved race
      specific elicitors of plant defenses and bacterial pectic enzymes. In
      collaboration with Brian J. Staskawicz and Frances Jurnak, respectively, Noel
      cloned the first avirulence gene and determined that pectate lyase C possessed a
      novel structural motif, known as the parallel beta-helix. Noel received his B.S.
      and M.S. from Iowa State University in Ames and his Ph.D. from the Department of
      Plant Pathology at the University of Wisconsin in Madison in 1968. He joined the
      faculty of the Department of Plant Pathology at the University of California at
      Riverside the same year and remained there his entire career. He served as Chair
      of the department from 1983 to 1989 and in 1997 assumed the William and Sue
      Johnson Endowed Chair in Molecular Plant Pathology. He became a Fellow of the
      American Phytopathological Society in 1991, a Fellow of the American Association
      for the Advancement of Science in 1996, a Fellow of the American Academy of
      Microbiology in 1997, and a member of the National Academy of Sciences in 1997.
      He was serving as President of the American Phytopathological Society (2001-2002)
      at the time of his death.

PMID- 17459001
TI  - Interstitial flow and its effects in soft tissues.
AB  - Interstitial flow plays important roles in the morphogenesis, function, and
      pathogenesis of tissues. To investigate these roles and exploit them for tissue
      engineering or to overcome barriers to drug delivery, a comprehensive
      consideration of the interstitial space and how it controls and affects such
      processes is critical. Here we attempt to review the many physical and
      mathematical correlations that describe fluid and mass transport in the tissue
      interstitium; the factors that control and affect them; and the importance of
      interstitial transport on cell biology, tissue morphogenesis, and tissue
      engineering. Finally, we end with some discussion of interstitial transport
      issues in drug delivery, cell mechanobiology, and cell homing toward draining
      lymphatics.

PMID- 17459003
TI  - Rac1 and RhoA GTPases have antagonistic functions during N-cadherin-dependent
      cell-cell contact formation in C2C12 myoblasts.
AB  - BACKGROUND INFORMATION: N-cadherin, a member of the Ca(2+)-dependent cell-cell
      adhesion molecule family, plays an essential role in the induction of the
      skeletal muscle differentiation programme. However, the molecular mechanisms
      which govern the formation of N-cadherin-dependent cell-cell contacts in
      myoblasts remain unexplored. RESULTS: In the present study, we show that N
      cadherin-dependent cell contact formation in myoblasts is defined by two stages.
      In the first phase, N-cadherin is highly mobile in the lamellipodia extensions
      between the contacting cells. The second stage corresponds to the formation of
      mature N-cadherin-dependent cell contacts, characterized by the immobilization of
      a pool of N-cadherin which appears to be clustered in the interdigitated membrane
      structures that are also membrane attachment sites for F-actin filaments. We also
      demonstrated that the formation of N-cadherin-dependent cell-cell contacts
      requires a co-ordinated and sequential activity of Rac1 and RhoA. Rac1 is
      involved in the first stage and facilitates N-cadherin-dependent cell-cell
      contact formation, but it is not absolutely required. Conversely, RhoA is
      necessary for N-cadherin-dependent cell contact formation, since, via ROCK (Rho
      associated kinase) signalling and myosin 2 activation, it allows the
      stabilization of N-cadherin at the cell-cell contact sites. CONCLUSIONS: We have
      shown that Rac1 and RhoA have opposite effects on N-cadherin-dependent cell-cell
      contact formation in C2C12 myoblasts and act sequentially to allow its formation.

PMID- 17459004
TI  - Is the anti-inflammatory effect of regular exercise responsible for reduced
      cardiovascular disease?
AB  - Engaging in regular physical activity reduces the risk of developing CVD
      (cardiovascular disease), but it is not certain to what degree this may be due to
      the anti-inflammatory effects of exercise. Following acute exercise, there is a
      transient increase in circulating levels of anti-inflammatory cytokines, whereas
      chronic exercise reduces basal levels of pro-inflammatory cytokines. Exercise
      training also induces the expression of antioxidant and anti-inflammatory
      mediators in the vascular wall that may directly inhibit the development of
      atherosclerosis. Limited studies in humans and more comprehensive assessments in
      animal models have confirmed that exercise is atheroprotective and helped
      identify a number of the mechanisms to explain these effects. This review
      explores the relationship between systemic and vascular wall inflammation and the
      role that the anti-inflammatory effects of exercise have on the development and
      progression of CVD.

PMID- 17459005
TI  - Gene therapy, bioengineered clotting factors and novel technologies for
      hemophilia treatment.
AB  - The World Federation of Hemophilia estimates that of the 400,000 individuals
      worldwide with hemophilia, 300,000 receive either no, or very sporadic,
      treatment. Thus, considerable innovation will be required to provide cost
      effective therapies/cures for all affected individuals. The high cost of
      prophylactic regimens hampers their widespread use, which further justifies the
      search for novel cost-effective therapies and ultimately a cure. Five gene
      transfer phase I clinical trials have been conducted using either direct in vivo
      gene delivery with viral vectors or ex vivo plasmid transfections and
      reimplantation of gene-engineered cells. Although there was evidence of gene
      transfer and therapeutic effects in some of these trials, stable expression of
      therapeutic factor VIII or FIX levels has not yet been obtained. Further
      improvements of the vectors and a better understanding of the immune consequences
      of gene transfer is warranted, as new trials are being initiated. Bioengineered
      clotting factors with increased stability and/or activity are being validated
      further in preclinical studies. Novel clotting factor formulations based on
      PEGylated liposomes with prolonged activities are being tested in the clinic, and
      are yielding encouraging results.

PMID- 17459006
TI  - Proteolysis of the endothelial cell protein C receptor by neutrophil proteinase
      3.
AB  - BACKGROUND: The endothelial cell protein C receptor (EPCR) presents protein C to
      the thrombin:thrombomodulin complex on the endothelium of large vessels, and
      enhances the generation of activated protein C (APC) and activation of protease
      activated receptor-1. A previous report has demonstrated binding of soluble (s)
      EPCR to activated neutrophils via surface proteinase 3 (PR3). METHODS: We now
      report further characterization of this interaction. Activated neutrophils and
      purified PR3 both decrease endothelial cell (EC) surface EPCR, suggestive of its
      proteolysis. RESULTS: When added to purified recombinant sEPCR, PR3 produced
      multiple cleavages, with early products including 20 kDa N-terminal and C
      terminal (after Lys(176)) fragments. The binding of active site blocked PR3 to
      sEPCR was studied by surface plasmon resonance. Estimates of the K(D) of 18.5-102
      nM were obtained with heterogeneous binding, suggestive of more than a single
      interaction site. CONCLUSIONS: This work demonstrates PR3 binding to and
      proteolysis of EPCR and suggests a mechanism by which anticoagulant and cell
      protective pathways can be down-regulated during inflammation.

PMID- 17459007
TI  - C1-inhibitor prevents non-specific plasminogen activation by a prourokinase
      mutant without impeding fibrin-specific fibrinolysis.
AB  - BACKGROUND: Prourokinase (prouPA) is unstable in plasma at therapeutic
      concentrations. A mutant form, M5, made more stable by reducing its intrinsic
      activity was therefore developed. Activation to two-chain M5 (tcM5) induced a
      higher catalytic activity than two-chain urokinase plasminogen activator (tcuPA),
      implicating an active site functional difference. Consistent with this, an
      unusual tcM5 complex with plasma C1-inhibitor was recently described in dog and
      human plasma. The effect of C1-inhibitor on fibrinolysis and fibrinogenolysis by
      M5 is the subject of this study. METHODS AND RESULTS: Zymograms of tcM5 and tcuPA
      incubated in plasma revealed prominent tcM5-C1-inhibitor complexes, which formed
      within 5 min. The inhibition rate by purified human C1-inhibitor (250 microg mL(
      1)) was about 7-fold faster for tcM5 than it was for tcuPA (10 microg mL(-1)).
      The effect of the inhibitor on the stability of M5 and prouPA was determined by
      incubating them in plasma at high concentrations (10-20 microg mL(-1)) +/- C1
      inhibitor supplementation. Above 10 microg mL(-1), depletion of all plasma
      plasminogen occurred, indicating plasmin generation and tcM5/tcuPA formation.
      With supplemental C1-inhibitor, M5 stability was restored but not prouPA
      stability. Clot lysis by M5 +/- supplemental C1-inhibitor showed no attenuation
      of the rate of fibrinolysis, whereas fibrinogenolysis was prevented by C1
      inhibitor. Moreover, because of higher dose-tolerance, the rate of fibrin
      specific lysis reached that achievable by non-specific fibrinolysis without
      inhibitor. CONCLUSIONS: Plasma C1-inhibitor stabilized M5 in its proenzyme
      configuration in plasma by inhibiting tcM5 and thereby non-specific plasminogen
      activation. At the same time, fibrin-specific plasminogen activation remained
      unimpaired. This unusual dissociation of effects has significant implications for
      improving the safety and efficacy of fibrinolysis.

PMID- 17459008
TI  - Determination of pediatric norms for assessment of upper venous system post
      thrombotic syndrome.

PMID- 17459012
TI  - Aberrant human tissue kallikrein levels in the stratum corneum and serum of
      patients with psoriasis: dependence on phenotype, severity and therapy.
AB  - BACKGROUND: Human tissue kallikreins (KLKs) are a family of 15 trypsin-like or
      chymotrypsin-like secreted serine proteases (KLK1-KLK15). Multiple KLKs have been
      quantitatively identified in normal stratum corneum (SC) and sweat as candidate
      desquamation-related proteases. OBJECTIVES: To quantify KLK5, KLK6, KLK7, KLK8,
      KLK10, KLK11, KLK13 and KLK14 in the SC and serum of patients with psoriasis, and
      their variation between lesional and nonlesional areas and with phenotype,
      therapy and severity. The overall SC serine protease activities were also
      measured. METHODS: Enzyme-linked immunosorbent assays and enzymatic assays were
      used. RESULTS: The lesional SC of psoriasis generally contained significantly
      higher levels of all KLKs. KLK6, KLK10 and KLK13 levels were significantly
      elevated even in the nonlesional SC. The overall trypsin-like, plasmin-like and
      furin-like activities were significantly elevated in the lesional SC. Plasmin
      like activity was significantly elevated also in the nonlesional SC. The SC
      chymotrypsin-like activity was only slightly elevated in psoriasis. KLK7 serum
      levels did not differ between normal volunteers and patients with psoriasis.
      Serum KLK6, KLK8, KLK10 and KLK13 levels in patients with untreated psoriasis
      significantly correlated with Psoriasis Area and Severity Index score. Serum KLK5
      and KLK11 levels decreased in patients with psoriasis after therapy, especially
      with etretinate. Patients with erythrodermic psoriasis exhibited significantly
      higher serum KLK levels than normal subjects or patients with psoriasis vulgaris
      or arthropathic psoriasis. CONCLUSIONS: We found aberrant KLK levels in the SC
      and serum of patients with psoriasis and suggest that KLKs might be involved in
      the pathogenesis of this disease.

PMID- 17459013
TI  - Reliability of self-reported willingness-to-pay and annual income in patients
      treated for toenail onychomycosis.
AB  - BACKGROUND: Willingness-to-pay (WTP) is a health economics measure that has
      recently been used for skin diseases to evaluate patients' quality of life.
      However, the reliability of this measure has not been investigated in the
      dermatology literature and is essential in validating its use in health services
      research. OBJECTIVES: This study evaluated the test-retest reliability of self
      reported annual income and WTP, a health economics measure of disease impact, in
      patients with toenail onychomycosis. METHODS: Forty-six patients enrolled in a
      randomized clinical trial comparing two different dosing regimens of terbinafine
      completed a self-administered questionnaire at baseline and 1 month later. The
      questionnaire asked: (i) how much patients would be willing to pay for a
      theoretical treatment with a cure rate of 85% for their current onychomycosis (10
      categories: $0-50, $51-100, to > $800); and (ii) annual income (10 categories: $0
      10,000 to > $200,000). RESULTS: Forty-four patients reported WTP at both visits,
      and 55% reported the same WTP. The quadratic-weighted (Fleiss-Cohen) kappa
      statistic indicated moderate agreement (kappa = 0.50, 95% confidence interval, CI
      0.24-0.75, P < 0.01) as did the Spearman rank-order correlation coefficient (r(s)
      = 0.57, P < 0.01; median difference = 0, P = 0.50). Strong agreement was shown
      among the 42 patients who reported income at both visits; 71% reported the same
      annual income category (kappa = 0.72, 95% CI 0.47-0.96, P < 0.01; r(s) = 0.68, P
      < 0.01; median difference = 0, P = 0.77). Age, disease severity and duration,
      previous therapy, self-reported annual income, and medication side-effects were
      not statistically associated with the reliability of WTP. CONCLUSIONS: WTP and
      annual income demonstrated moderate and strong test-retest reliability,
      respectively. Self-reported WTP can serve as a reliable measure for future health
      economics research on onychomycosis.

PMID- 17459014
TI  - Mitochondrial DNA analyses of Indian water buffalo support a distinct genetic
      origin of river and swamp buffalo.
AB  - Water buffalo (Bubalus bubalis) is broadly classified into river and swamp
      categories, but it remains disputed whether these two types were independently
      domesticated, or if they are the result of a single domestication event. In this
      study, we sequenced the mitochondrial D-loop region and cytochrome b gene of 217
      and 80 buffalo respectively from eight breeds/locations in northern, north
      western, central and southern India and compared our results with published
      Mediterranean and swamp buffalo sequences. Using these data, river and swamp
      buffalo were distinguished into two distinct clades. Based upon the existing
      knowledge of cytogenetic, ecological and phenotypic parameters, molecular data
      and present-day distribution of the river and swamp buffalo, we suggest that
      these two types were domesticated independently, and that classification of the
      river and swamp buffalo as two related subspecies is more appropriate.

PMID- 17459015
TI  - The extent of linkage disequilibrium in a large cattle population of western
      Africa and its consequences for association studies.
AB  - Several previous studies concluded that linkage disequilibrium (LD) in livestock
      populations from developed countries originated from the impact of strong
      selection. Here, we assessed the extent of LD in a cattle population from western
      Africa that was bred in an extensive farming system. The analyses were performed
      on 363 individuals in a Bos indicus x Bos taurus population using 42
      microsatellite markers on BTA04, BTA07 and BTA13. A high level of expected
      heterozygosity (0.71), a high mean number of alleles per locus (9.7) and a mild
      shift in Hardy-Weinberg equilibrium were found. Linkage disequilibrium extended
      over shorter distances than what has been observed in cattle from developed
      countries. Effective population size was assessed using two methods; both methods
      produced large values: 1388 when considering heterozygosity (assuming a mutation
      rate of 10(-3)) and 2344 when considering LD on whole linkage groups (assuming a
      constant population size over generations). However, analysing the decay of LD as
      a function of marker spacing indicated a decreasing trend in effective population
      size over generations. This decrease could be explained by increasing selective
      pressure and/or by an admixture process. Finally, LD extended over small
      distances, which suggested that whole-genome scans will require a large number of
      markers. However, association studies using such populations will be effective.

PMID- 17459016
TI  - Somatic cell hybrid and RH mapping of the porcine LGALS1, ITGA7, ITGB1, LGALS3,
      NOL12, GGA1, SH3BP1 and PDXP genes.

PMID- 17459017
TI  - A genome scan reveals QTL for growth, fatness, leanness and meat quality in a
      Duroc-Pietrain resource population.
AB  - We performed a genome-wide QTL scan for production traits in a line cross between
      Duroc and Pietrain breeds of pigs, which included 585 F(2) progeny produced from
      31 full-sib families genotyped with 106 informative microsatellites. A linkage
      map covering all 18 autosomes and spanning 1987 Kosambi cM was constructed.
      Thirty-five phenotypic traits including body weight, growth, carcass composition
      and meat quality traits were analysed using least square regression interval
      mapping. Twenty-four QTL exceeded the genome-wide significance threshold, while
      47 QTL reached the suggestive threshold. These QTL were located at 28 genomic
      regions on 16 autosomal chromosomes and QTL in 11 regions were significant at the
      genome-wide level. A QTL affecting pH value in loin was detected on SSC1 between
      marker-interval S0312-S0113 with strong statistical support (P < 3.0 x 10(-14));
      this QTL was also associated with meat colour and conductivity. QTL for carcass
      composition and average daily gain was also found on SSC1, suggesting multiple
      QTL. Seventeen genomic segments had only a single QTL that reached at least
      suggestive significance. Forty QTL exhibited additive inheritance whereas 31 QTL
      showed (over-) dominance effects. Two QTL for trait backfat thickness were
      detected on SSC2; a significant paternal effect was found for a QTL in the IGF2
      region while another QTL in the middle of SSC2 showed Mendelian expression.

PMID- 17459018
TI  - QTL modulating ear size and erectness in pigs.
AB  - Ear size and erectness are important conformation measurements in pigs. An F(2)
      population established by crossing European Large White (small, erect ears) with
      Chinese Meishan (large, flop ears) was used to study the genetic influence of the
      two ear traits for the first time. A linkage map incorporating 152 markers on 18
      autosomal chromosomes was utilised in a genome scan for QTL. Significant QTL were
      found on SSC1, 5, 7, 9 and 12 for the two traits. The QTL on SSC5 and SSC7 had
      major effects and were significant at the genome-wide level (P < 0.01). The QTL
      on SSC1 for ear erectness also had a major effect and was genome-wide significant
      (P < 0.01). The 95% confidence interval (CI) of the ear size QTL on SSC5 spanned
      only 4 cM. The QTL on SSC7 for the two ear traits each had a CI of <20 cM, and
      their positions overlapped with those of the major QTL affecting subcutaneous fat
      depths on the same chromosome. This study provides insights on the complex
      genetic influences underlying pig ear traits and will facilitate positional
      candidate gene analysis to identify causative DNA variants.

PMID- 17459019
TI  - Genetic relationships between feral cattle from Chirikof Island, Alaska and other
      breeds.
AB  - The origin of cattle on Chirikof Island, off the coast of Alaska, is not well
      documented. We assessed genetic differentiation of cattle isolated on Chirikof
      Island from several breeds commonly used for commercial production in North
      America including breeds popularly believed to have contributed to the Chirikof
      Island population. A set of 34 microsatellite loci was used to genotype Angus,
      Charolais, Hereford, Highland, Limousin, Red Angus, Salers, Shorthorn, Simmental,
      Tarentaise and Texas Longhorn cattle sampled from North America and the Chirikof
      Island population. Resulting F(ST) statistics for these loci ranged from 0.06 to
      0.22 and on average, 14% of total genetic variation was between breeds. Whether
      population structure was modelled as a bifurcating tree or genetic network,
      Chirikof Island cattle appeared to be unique and strongly differentiated relative
      to the other breeds that were sampled. Bayesian clustering for multiple-locus
      assignment to genetic groups indicated low levels of admixture in the Chirikof
      Island population. Thus, the Chirikof Island population may be a novel genetic
      resource of some importance for conservation and industry.

PMID- 17459020
TI  - Detection of parvovirus B19 nucleic acids and expression of viral VP1/VP2 antigen
      in human colon carcinoma.
AB  - OBJECTIVES: The aim of this study was to evaluate whether parvovirus B19, a
      common infectious pathogen in humans, also was involved in human colon carcinoma.
      METHODS: A total of 119 paraffin-embedded specimens of colon polyps,
      adenocarcinomas, carcinoma-adjacent tissues, and normal controls were processed
      for nested polymerase chain reaction (PCR), in situ hybridization (ISH),
      immunohistochemistry (IHC), and laser capture micro dissection detection of B19
      DNA and protein. The expression of cyclo-oxygenase-2 (COX-2) in the colon- cancer
      cells (Lovo) transfected by inducible vector for VP1u was determined by western
      blot analysis. RESULTS: B19 DNA was detected in 94.6% (35/37) of colon
      adenocarcinomas, 67.6% (25/37) of adjacent noncancerous tissues, 85.6% (30/35) of
      polyps, and 60.0% (6/10) of normal controls by nested PCR, respectively. Analysis
      of the microdissected material confirmed the presence of viral DNA in colonic
      neoplastic epithelium. ISH detected B19 DNA in 81.1% (30/37) of colon
      adenocarcinomas, 43.2% (16/37) of adjacent noncancerous tissues, 74.3% (26/35) of
      polyps, and 50.0% (5/10) of normal controls, respectively. B19 protein VP1/VP2
      was found in 78.4% (29/37), 32.4% (12/37), and 57.1% (20/35) of colon
      adenocarcinomas, tumor-adjacent tissues, and polyps, respectively, but not in
      normal colons (none of 10). There were significant differences in nested PCR,
      ISH, and IHC between adenocarcinoma and non-neoplastic adjacent tissues, and
      between adenocarcinoma and normal controls. Transfection of colon-cancer cells
      (Lovo) by inducible vector for VP1u resulted in marked upregulation of cyclo
      oxygenase-2 proteins. CONCLUSIONS: Parvovirus B19 nucleic acids commonly exist in
      human colon tissues and VP1/VP2 antigen is preferentially located in colon polyps
      and adenocarcinomas lesions. B19 viral products VP1u may induce important
      oncogenic pathways in colon-cancer cells.

PMID- 17459022
TI  - Video capsule enteroscopy in the diagnosis of celiac disease: a multicenter
      study.
AB  - OBJECTIVES: Duodenal biopsy is the current gold standard for diagnosis of celiac
      disease. Videocapsule endoscopy examines the entire small bowel and allows
      visualization of mucosal villi. We evaluated the potential of videocapsule
      endoscopy in assessing the severity and extent of mucosal changes in patients
      with suspected celiac disease. METHODS: Consecutive patients with signs/symptoms
      suggesting celiac disease and positive anti-gliadin and/or anti-endomysial and/or
      anti-tissue transglutaminase antibodies underwent upper gastrointestinal
      endoscopy and videocapsule endoscopy. Duodenal biopsies were classified according
      to modified Marsh's criteria. Capsule findings were evaluated for the presence of
      lesions compatible with celiac disease (scalloping of duodenal folds, fissures,
      flat mucosa, and mosaic appearance). RESULTS: Forty-three patients were studied.
      Duodenal histology was normal in 11 and compatible with celiac disease in 32.
      Using duodenal histology as the gold standard, the performance characteristics of
      capsule endoscopy for the diagnosis of celiac disease were: sensitivity 87.5%
      (95% CI 76.1-98.9%), specificity 90.9% (95% CI 81.0-100%), positive predictive
      value 96.5% (95% CI 90.1-100%), negative predictive value 71.4% (95% CI 55.8
      87%), positive and negative likelihood ratios 9.6 and 0.14, respectively.
      Eighteen patients had mucosal changes extending beyond the duodenum, involving
      the entire small bowel in three. These patients tended to have more severe
      symptoms, but the difference was not statistically significant. Interobserver
      agreement for the diagnosis of celiac disease by capsule endoscopy ranged between
      79.2 and 94.4%; kappa values ranged between 0.56 and 0.87. CONCLUSIONS:
      Videocapsule endoscopy shows good sensitivity and excellent specificity for the
      detection of villous atrophy in patients with suspected celiac disease.

PMID- 17459021
TI  - Plasma citrulline concentration: a reliable marker of small bowel absorptive
      capacity independent of intestinal inflammation.
AB  - OBJECTIVES: Postabsorptive plasma citrulline concentration has been proposed as a
      reliable marker of small bowel absorptive capacity in short bowel patients. The
      aim of this study was to address the potentially confounding impact of intestinal
      inflammation. METHODS: Fifty-five patients were selected according to diagnosis,
      small bowel length, and degree of bowel inflammation. (a) Crohn's disease (CD)
      with massive small bowel resection leaving </=50 cm (N = 6), (b) CD with 50-150
      cm remaining (N = 9), (c) CD with no resection but active inflammation (high C
      reactive protein [CRP] and Crohn's Disease Activity Index [CDAI] >220) (N = 7),
      (d) CD without resection or active inflammation (normal CRP and CDAI <150) (N =
      9), (e) mesenteric infarction (MI) with resection leaving </=50 cm (N = 6), (f)
      MI leaving 50-150 cm (N = 6), (g) active celiac disease (N = 6), (h) healthy
      volunteers (N = 6). Postabsorptive fasting plasma citrulline was measured using
      reverse-phase, high performance liquid chromatography. Absorptive capacity and
      permeability were also measured after oral sugar-mix ingestion (5 g lactulose, 1
      g L-rhamnose, 0.5 g D-xylose). RESULTS: The plasma citrulline strongly correlated
      with small bowel length (P < 0.0001) and xylose absorption (P < 0.001). No
      correlation was found with CDAI, permeability, CRP, albumin, sedimentation rate,
      white cell count, or platelet count. Citrulline was significantly higher (P <
      0.0004) in CD and MI patients with a remnant small bowel length of 50-150 cm
      (mean 21.0 micromol/L) than in those with length </=50 cm (mean 9.2 micromol/L).
      CONCLUSIONS: Plasma citrulline concentration is a simple and reliable surrogate
      for small bowel absorptive capacity and is not influenced by intestinal
      inflammation.

PMID- 17459023
TI  - Ursodeoxycholic acid for patients with primary biliary cirrhosis: an updated
      systematic review and meta-analysis of randomized clinical trials using Bayesian
      approach as sensitivity analyses.
AB  - OBJECTIVES: Ursodeoxycholic acid (UDCA) is used for primary biliary cirrhosis
      (PBC), but the beneficial effects remain controversial. METHODS: We performed an
      updated systematic review to evaluate the benefits and harms of UDCA in patients
      with PBC. We included randomized clinical trials evaluating UDCA versus placebo
      or no intervention in patients with PBC. The primary outcomes, mortality and
      mortality or liver transplantation, were reported as relative risk (RR) with 95%
      confidence interval (CI). Meta-regression was used to investigate the
      associations between UDCA effects and the trial's risk of bias, UDCA dose,
      duration, and PBC severity at trial entry. We used Bayesian meta-analytic
      approaches as sensitivity analyses. RESULTS: Sixteen randomized clinical trials
      (1,447 patients) evaluating UDCA versus placebo or no intervention were
      identified. Over half of the trials had high risk of bias. Comparing with placebo
      or no intervention, UDCA did not significantly affect mortality (RR 0.97, 95% CI
      0.67-1.42) and mortality or liver transplantation (RR 0.92, 95% CI 0.71-1.21).
      The findings were supported by the Bayesian meta-analyses. Meta-regression
      analyses suggested that UDCA effects seem to be associated with patient's disease
      severity and trial duration. UDCA did not improve pruritus, fatigue, autoimmune
      conditions, liver histology, or portal pressure. UDCA seemed to improve
      biochemical variables, such as serum bilirubin, and ascites and jaundice, but the
      findings were based on few trials with sparse data. The use of UDCA was
      significantly associated with adverse events, mainly weight gain. CONCLUSIONS:
      This updated systematic review did not demonstrate any benefit of UDCA on
      mortality and mortality or liver transplantation in patients with PBC.

PMID- 17459024
TI  - Subsite-specific risk factors for esophageal and gastric adenocarcinoma.
AB  - BACKGROUND: The incidence rates of adenocarcinoma involving specific gastric and
      esophageal subsites are changing significantly, but the risk factors associated
      with those subsite changes remain controversial. We aimed to describe the site
      specific risk factors associated with adenocarcinoma of the stomach and
      esophagus. METHODS: Using the Rochester Epidemiology Project, all cases of
      gastric and esophageal adenocarcinoma among Olmsted County, Minnesota, residents
      first diagnosed between 1971 and 2000 were identified. Complete inpatient and
      outpatient records were reviewed and specific subsites defined. Risk factors were
      assessed in cases, and age- and sex-matched controls. RESULTS: A total of 186
      incident cases of gastric or esophageal adenocarcinoma were identified between
      1971 and 2000, in Olmsted County. Gastroesophageal reflux disease (GERD) was a
      significant risk factor for both esophageal (OR 5.5, 95% CI 1.2-25) and
      esophagogastric junction adenocarcinoma (OR 13.0, 95% CI 1.7-99), but not for
      either proximal or distal gastric cancer. Smoking (OR 2.8, 95% CI 1.0-7.8) was
      associated with distal gastric cancer. Proton pump inhibitor (PPI) exposure was
      limited and was not a significant risk factor at any subsite. CONCLUSIONS: This
      identification of distinct risk factors by subsite supports the concept that
      esophageal and gastric adenocarcinomas are two different diseases. Adenocarcinoma
      of the junction is probably a form of esophageal cancer and should not be coded
      with gastric neoplasms.

PMID- 17459025
TI  - The diagnostic accuracy of esophageal capsule endoscopy in patients with
      gastroesophageal reflux disease and Barrett's esophagus: a blinded, prospective
      study.
AB  - BACKGROUND: Esophageal capsule endoscopy (ECE) is a novel technique that offers
      noninvasive evaluation of esophageal pathology in gastroesophageal reflux disease
      (GERD) patients. OBJECTIVE: To assess the diagnostic accuracy of ECE for
      Barrett's esophagus (BE), erosive esophagitis, and hiatal hernia and to assess
      the safety profile of ECE. METHODS: Patients with GERD symptoms and those
      undergoing BE surveillance were prospectively enrolled. All patients underwent
      ECE followed by standard upper endoscopy. ECE findings were interpreted by
      examiners blinded to endoscopy results. The gold standard was the findings at
      endoscopy and ECE results were compared with those at endoscopy. RESULTS: One
      hundred patients were enrolled of which 94 completed the study. At upper
      endoscopy, BE was suspected in 53 (mean length 3.1 cm) and confirmed in 45
      patients. Erosive esophagitis and hiatal hernia were identified in 18 and 70
      patients, respectively. The sensitivity, specificity, positive predictive value
      (PPV), and negative predictive value (NPV) of ECE for BE in GERD patients were
      67%, 87%, 60%, and 90%, respectively. The sensitivity, specificity, PPV, and NPV
      of ECE for BE patients undergoing surveillance were 79%, 78%, 94%, and 44%,
      respectively. The sensitivity, specificity, PPV, and NPV for erosive esophagitis
      were 50%, 90%, 56%, and 88% and for hiatal hernia were 54%, 67%, 83%, and 33%,
      respectively. CONCLUSIONS: Current diagnostic rates of ECE for BE are not yet
      accurate enough for application in clinical practice. An improvement in
      technology and learning curve assessments are required, until then standard upper
      endoscopy remains the gold standard.

PMID- 17459026
TI  - Utilization of health-care resources by patients with IBD in Manitoba: a profile
      of time since diagnosis.
AB  - OBJECTIVES: We tested the hypothesis of nonlinear longitudinal trends in health
      care utilization by individuals with Crohn's disease (CD) and ulcerative colitis
      (UC) in Manitoba. METHODS: Administrative databases were used to report resource
      use in 2000/1. A total of 5,485 cases of CD and UC and 45,279 matched controls
      were separated into incident cases (0-2 yr of disease), cases with longstanding
      disease (3-10 yr), and cases with very longstanding disease (>10 yr). Relative
      risk ratios (RRR) indicating the likelihood of resource use, given disease
      duration, were computed using multinomial logistic regression analysis.
      Sensitivity analysis was conducted to test the robustness of results to altering
      the disease duration cutoffs. RESULTS: Independent of disease duration, in
      general, outpatient utilization was over twice as likely among IBD cases compared
      with controls whether or not the contact was made for IBD-specific reasons. The
      likelihood of utilization was greatest among incident cases for outpatient visits
      with an internist (RRR 6.16, 95% CI 5.11-7.43) and surgical visits (RRR 3.78, 95%
      CI 3.14-4.55). Inpatient stays for IBD-specific reasons in general were
      considered dependent on disease duration; in particular, there was a fourfold
      higher likelihood for the incident cases relative to their controls. For non-IBD
      specific reasons, IBD cases were 1.5 times as likely to have inpatient stays,
      regardless of disease duration. CONCLUSIONS: Our results suggest that within the
      first 2 yr from disease diagnosis the most costly resources were employed. We can
      likely measure the greatest proportion of treatment effects on resource use
      within a relatively short period.

PMID- 17459027
TI  - Preferential induction of peripheral lymph node addressin on high endothelial
      venule-like vessels in the active phase of ulcerative colitis.
AB  - OBJECTIVES: In the colonic mucosa with ulcerative colitis (UC), it has been
      suggested that L-selectin-peripheral lymph node addressin (PNAd) interaction
      plays a role in lymphocyte recruitment, which requires PNAd induction on high
      endothelial venule (HEV)-like vessels. The present study was undertaken to
      elucidate how these HEV-like vessels participate in the pathogenesis of UC and
      also to determine whether the presence of such vessels is correlated with
      clinical outcomes. METHODS: Biopsy specimens composed of active (N = 32) and
      remission (N = 12) phases of UC were subjected to immunohistochemistry for CD34,
      MECA-79, and HECA-452, and the immunostained sections were quantitatively
      analyzed. An in vitro binding assay with L-selectin*IgM chimeric protein was
      carried out to determine whether PNAd on HEV-like vessels formed in UC functions
      as an L-selectin ligand. RT-PCR was carried out to determine which enzyme is
      upregulated for PNAd biosynthesis on HEV-like vessels induced in the active phase
      of UC. Triple immunostaining for MECA-79 together with CD3 and CD20/CD79alpha,
      CD4 and CD8, or CXCR3 and ST2L was carried out to determine which lymphocyte
      population closely associates with these vessels. RESULTS: PNAd-expressing HEV
      like vessels were preferentially induced in the active phase of UC with increased
      transcription of the gene encoding N-acetylglucosamine-6-O-sulfotransferase
      (GlcNAc6ST)-1, which directs expression of the MECA-79 epitope. Moreover, T
      cells, particularly CD4(+) T cells, were more closely associated with these HEV
      like vessels than B cells. CONCLUSIONS: T-cell recruitment via PNAd-expressing
      HEV-like vessels induced by expression of GlcNAc6ST-1 may play a role in UC
      pathogenesis.

PMID- 17459028
TI  - Incidence of endophthalmitis after cataract surgery in Japan.
AB  - PURPOSE: To estimate the incidence rate of endophthalmitis after cataract surgery
      performed by Japanese surgeons. METHODS: A sample of 20% of members of the
      Japanese Society of Ophthalmic Surgeons was randomly selected. Each member was
      sent a postal survey asking for information on the number of cataract surgeries
      performed in 2003 and the number of postsurgery cases of endophthalmitis.
      RESULTS: Replies were received from 78.7% (513/652) of survey recipients. The
      total number of cataract surgeries was 100 539, among which 52 cases of
      endophthalmitis occurred, resulting in an overall incidence rate of 0.052%.
      Incidence rates were 0.049% (38/78 170) for scleral incision phacoemulsification
      and 0.043% (9/20 894) for clear corneal incision phacoemulsification, with no
      significant difference between groups. The average annual volumes of surgery were
      210 and 280 cases for surgeons who preferred scleral incision and clear corneal
      incision, respectively. There was a significant difference between volumes
      (Student's t-test, p < 0.01). The incidence of endophthalmitis was significantly
      lower with high-volume (> 300 cases/year) surgeons than with low-volume (< or =
      300 cases/year) surgeons (0.040% versus 0.066%, chi-square test, p < 0.05).
      CONCLUSIONS: The incidence of endophthalmitis after cataract surgery in Japan as
      estimated by a postal survey was low (0.052%) and consistent with rates reported
      previously. Surgeons who preferred clear corneal incision performed significantly
      more surgeries annually, but the incidence of endophthalmitis was similar between
      scleral and clear corneal incision phacoemulsification surgery.

PMID- 17459029
TI  - Entry-site-related retinal detachment after pars plana vitrectomy.
AB  - PURPOSE: Today, pars plana vitrectomy represents a standard surgical procedure
      for a number of retinal diseases that were previously considered inoperable. The
      aim of the present study is to investigate the entry site of pars plana
      vitrectomy as a possible source of retinal detachment. METHODS: We reviewed
      retrospectively all cases of uncomplicated pars plana vitectomies because of
      macular hole, macular pucker and diabetic macular oedema performed in our
      department between 1 January 2001 and 7 July 2004. RESULTS: Over 3.5 years, 244
      pars plana vitrectomies because of macular disease were performed. Sclerotomy
      related retinal detachment was observed in 11 (4.5%) cases. These retinal
      detachments occurred at a mean of 37 (2-100) days after surgery. They appeared
      within the first 4 weeks in 55% of the cases. CONCLUSION: Iatrogenic retinal
      breaks and detachment continue to be a severe complication of pars plana
      vitrectomy, despite improvements in instrumentation and surgical techniques. A
      4.5% incidence of sclerotomy-related retinal detachment after simple vitrectomy
      calls for action. Current approaches to reduce this complication - such as
      circular peripheral cryoretinopexy, scleral buckling or 360 degrees laser
      treatment - are invasive. We recommend extended vitreous base cleaning with
      scleral indentation and examination of the entry sites, performed with a three
      mirror lens or via careful indirect ophthalmoscopy into the periphery, 4 weeks
      after surgery.

PMID- 17459030
TI  - Full-thickness macular hole in a patient with diabetic cystoid macular oedema
      treated by intravitreal triamcinolone injections.
AB  - PURPOSE: Full-thickness macular hole associated with diabetic macular oedema is a
      rare feature and its pathogenesis remains incompletely elucidated. We report the
      occurrence of a full-thickness macular hole, documented with optical coherence
      tomography (OCT), in a patient with diabetic cystoid macular oedema treated by
      intravitreal triamcinolone injections. CASE REPORT: A 48-year-old woman with
      refractory diabetic cystoid macular oedema underwent successive intravitreal
      triamcinolone injections, which were followed by a progressive thinning of the
      neurosensory retina at the fovea, and then by a full-thickness macular hole,
      associated with a perifoveal posterior hyaloid detachment, visible on OCT. During
      pars plana vitrectomy, a thin epiretinal macular membrane was diagnosed and
      removed. DISCUSSION: Pathogenesis of the present full-thickness macular hole
      associated with diabetic macular oedema is different from that of idiopathic
      macular holes because anteroposterior vitreous tractions were not involved in its
      formation. Recurrent intravitreal triamcinolone injections may have had an
      indirect role in the development of the macular hole, by favouring the rupture of
      distended Muller cells and intraretinal pseudocysts.

PMID- 17459031
TI  - Anti-inflammatory efficacy of a single posterior subtenon injection of
      triamcinolone acetonide versus prednisolone acetate 1% eyedrops after pars plana
      vitrectomy.
AB  - PURPOSE: To compare the safety and anti-inflammatory efficacy of a single
      posterior subtenon injection of triamcinolone acetonide (TA) with prednisolone
      acetate 1% eyedrops after pars plana vitrectomy (PPV). METHODS: The study
      included 40 consecutive phakic eyes of 40 patients undergoing PPV for non
      clearing vitreous haemorrhage with attached retina (verified by echography),
      epiretinal membrane or macular hole. At the end of the surgical procedure, eyes
      were randomized to receive either a single posterior subtenon injection of TA (40
      mg in 1 ml) plus sham eyedrops (prednisolone acetate 1% vehicle) postoperatively
      (group TA), or a posterior subtenon sham injection (1 ml balanced salt solution)
      plus prednisolone acetate 1% eyedrops postoperatively (group ED). RESULTS: There
      was no difference in the severity of anterior chamber cell and flare between the
      two groups at any time-point during the study period (p > 0.05). Separate within
      group analysis revealed a significant decrease in anterior chamber cell and flare
      from postoperative day 1 to postoperative days 7, 14 and 28 in both groups (p <
      0.05). There was no difference in pain, photophobia, conjunctival erythema,
      ciliary flush or chemosis scores between the two groups at any time-point during
      the study period (p > 0.05). Steroid-induced intraocular hypertension was not
      observed in either group. CONCLUSIONS: A single posterior subtenon injection of
      TA can be as effective and safe as a 4-week regimen of prednisolone acetate 1%
      eyedrops in controlling intraocular inflammation after PPV.

PMID- 17459032
TI  - Annular elastolytic giant cell granuloma: a prodromal stage of mid-dermal
      elastolysis?

PMID- 17459033
TI  - Extracorporeal photopheresis in combination with bexarotene in the treatment of
      mycosis fungoides and Sezary syndrome.

PMID- 17459034
TI  - A large foot ulcer due to disseminated Mycobacterium avium infection in a patient
      with previously undiagnosed HIV infection.

PMID- 17459035
TI  - Hutchinson-Gilford progeria syndrome: clinical findings in three patients
      carrying the G608G mutation in LMNA and review of the literature.
AB  - BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature
      ageing disorder that belongs to a group of conditions called laminopathies which
      affect nuclear lamins. Classical and atypical forms of HGPS have been reported
      and there are clinical overlaps with mandibulo-acral dysplasia and restrictive
      dermopathy. To date, mutations in two genes, LMNA and ZMPSTE24, have been found
      in patients with HGPS. The p.G608G LMNA mutation is the most commonly reported
      mutation. Correlations between genotype and phenotype in children with progeroid
      syndromes are beginning to emerge. OBJECTIVES: To establish whether the LMNA
      p.G608G mutation is associated with a particular phenotype of HGPS. METHODS: We
      reviewed the clinical features and skin histology of three children with HGPS
      associated with the p.G608G LMNA mutation, and compared our findings with those
      reported in the literature. RESULTS: Our patients shared a very similar
      presentation and clinical course. Skin changes were the earliest finding in all
      three. Skin histology showed nonspecific changes only. CONCLUSIONS: The LMNA
      p.G608G mutation results in a uniform phenotype through early to mid-childhood,
      in keeping with that described in classical HGPS. Skin changes are the earliest
      distinctive clinical finding and should prompt careful physical and radiological
      examination for other features of HGPS. Skin biopsy for histology is not a useful
      investigation when a diagnosis of HGPS is suspected.

PMID- 17459036
TI  - Oral R115866 in the treatment of moderate to severe facial acne vulgaris: an
      exploratory study.
AB  - BACKGROUND: R115866 (Rambazole; Barrier Therapeutics NV, Geel, Belgium), a new
      generation retinoic acid metabolism-blocking agent, is a nonretinoid compound
      enhancing intracellularly the endogenous levels of all-trans-retinoic acid by
      blocking its catabolism. By virtue of this property, and the proven positive
      effects of retinoids in the treatment of acne, R115866 could potentially be a
      useful drug for acne. OBJECTIVES: To explore the efficacy, safety and
      tolerability of systemic R115866 in male patients with moderate to severe facial
      acne vulgaris (at least 15 papules and/or pustules and at least two nodulocystic
      lesions). METHODS: In this exploratory trial, 17 patients were treated with oral
      R115866 1 mg once daily for 12 weeks, followed by a 4-week treatment-free period.
      RESULTS: At the end of treatment (week 12, n = 16) a mean reduction in
      inflammatory lesion count of 77.4% (P < 0.001), in noninflammatory lesion count
      of 58.3% (P < 0.001) and in total lesion count of 76.0% (P < 0.001) was observed
      as compared with baseline. All lesion counts were significantly reduced from week
      4 onwards. Mild side-effects were reported occasionally. CONCLUSIONS: The current
      data indicate that treatment with oral R115866 1 mg once daily for 12 weeks in
      patients with moderate to severe facial acne vulgaris is efficacious and well
      tolerated and merits further investigation.

PMID- 17459037
TI  - Yellow nail syndrome: not a genetic disorder? Eleven new cases and a review of
      the literature.
AB  - BACKGROUND: Yellow nail syndrome (YNS) is characterized by the triad of
      characteristic nail changes, chronic respiratory disorders and primary
      lymphoedema. Over 100 cases have been published, most of which have been
      sporadic. Despite this, YNS is classified as a dominantly inherited lymphoedema
      with variable expression. There have been only a few published reports where a
      positive family history (FH) has been documented in cases of YNS. OBJECTIVES: To
      conduct a retrospective survey investigating the genetic basis of YNS. METHODS:
      The notes of 11 patients diagnosed with YNS were examined for documentation of a
      positive FH, and in addition a postal questionnaire was sent to these patients.
      RESULTS: Only one of the 11 patients had a relevant FH. In addition, four
      patients had complete recovery of their nail changes. CONCLUSIONS: This is the
      first retrospective study of YNS to document clear remission of nail changes. The
      lack of a positive FH in the majority of patients in our study, the late onset of
      the disease and recovery of nail changes in our patients suggest that YNS may not
      be primarily a genetic disease as it is currently classified.

PMID- 17459038
TI  - Acute 'relaxer'-associated scarring alopecia: a report of five cases.

PMID- 17459039
TI  - Successful treatment of cutaneous lesions in juvenile dermatomyositis with high
      dose intravenous immunoglobulin.

PMID- 17459040
TI  - Pterygium unguis formation in porokeratosis of Mibelli.

PMID- 17459041
TI  - DNase1L2 suppresses biofilm formation by Pseudomonas aeruginosa and
      Staphylococcus aureus.
AB  - BACKGROUND: The formation of biofilms, which is an important step in bacterial
      colonization, can be inhibited by deoxyribonuclease (DNase)-mediated breakdown of
      extracellular DNA. We have recently demonstrated that epidermal keratinocytes
      strongly express DNase1-like 2 (DNase1L2) in a differentiation-associated manner.
      OBJECTIVES: To determine whether enzymatically active DNase1L2 is present in
      human stratum corneum and whether it is able to suppress bacterial biofilm
      formation. METHODS: DNase1L2 was extracted from normal human stratum corneum,
      immunocaptured and incubated with plasmid DNA. DNA hydrolysis was monitored by
      gel electrophoresis and ethidium bromide staining. The effect of DNase1L2 on
      biofilm formation was assayed by cultivation of Pseudomonas aeruginosa and
      Staphylococcus aureus in the presence or absence of purified recombinant DNase1L2
      in microtitre plates and subsequent quantification of biofilm-forming bacteria by
      crystal violet staining. RESULTS: DNase1L2 was found to be present in an
      enzymatically active form in the stratum corneum of human skin. In an in vitro
      assay, purified recombinant DNase1L2 efficiently suppressed the formation of
      biofilms by P. aeruginosa and S. aureus. CONCLUSIONS: Our data suggest that
      DNase1L2 is a novel component of the innate antimicrobial defence of the
      epidermis.

PMID- 17459042
TI  - Cosmetic surgery: who needs surgeons when you've got creams?

PMID- 17459043
TI  - Use of oral glycopyrronium bromide in hyperhidrosis.
AB  - BACKGROUND: Idiopathic hyperhidrosis may be a disabling condition causing
      emotional stress and negative impact on a patient's quality of life. Oral
      anticholinergics are one of the treatments available. There are few published
      data on the use of the anticholinergic drug glycopyrronium bromide
      (glycopyrrolate) given orally in the treatment of hyperhidrosis. OBJECTIVES: To
      report a retrospective analysis describing the treatment responses, doses and
      side-effects of oral glycopyrrolate in the treatment of idiopathic hyperhidrosis.
      METHODS: Review of case notes in a series of 24 patients, nine with generalized
      and 15 with localized hyperhidrosis. RESULTS: Fifteen of 19 evaluable patients
      (79%) responded to oral glycopyrrolate. However, treatment was limited by side
      effects in around one third of patients. CONCLUSIONS: A prospective clinical
      study to compare the efficacy and side-effects of oral anticholinergics is
      warranted.

PMID- 17459044
TI  - Psoriasis has a major secondary impact on the lives of family members and
      partners.
AB  - BACKGROUND: Psoriasis affects the quality of life (QoL) of relatives and partners
      of patients with psoriasis, but little is known about this secondary impact.
      OBJECTIVES: To identify the different ways in which the lives of relatives and
      partners of people with psoriasis are affected by the disease. METHODS: Relatives
      and partners of patients with psoriasis participated. Subjects were excluded if
      they had any skin disease. The severity of the psoriasis of the patients was
      measured using the Psoriasis Area and Severity Index (PASI), Dermatology Life
      Quality Index (DLQI) and Psoriasis Disability Index (PDI). Subjects either had
      intensive qualitative interviews with one researcher or responded to a postal
      questionnaire. Both methods identified ways in which their relative's or
      partner's psoriasis had affected their lives. RESULTS: Thirty-three subjects were
      interviewed and 30 replied by postal questionnaire. Twenty-eight of the 63
      subjects were relatives (seven men and 21 women) and 35 were partners (16 men and
      19 women). The median age was 51 years (range 20-80). The patients (n = 63) had a
      mean DLQI of 10, mean PDI of 13.8 and mean PASI of 5.2. Forty different aspects
      of QoL impairment of relatives and partners were identified. The percentage of
      subjects in whom any of these aspects were mentioned is illustrated in six
      different categories. Seventy per cent stated that the treatment of their
      relative or partner resulted in them having to spend extra time on housework; 57%
      described psychological pressures including anxiety, being upset and being
      worried about the patient's future; 55% described social disruption due to lack
      of social confidence either because of embarrassment or because of the time
      required for care duties; 44% described limitations to holiday plans, sport and
      leisure activities and evenings out; 37% described limitations on their daily
      activities such as shopping, work and time spent with other family members; 37%
      felt that their close relationships had deteriorated. Only 8% described no effect
      at all on their QoL. The QoL of the relatives and partners (number of categories
      affected) was more closely related to the patients' QoL (DLQI: r = 0.77, P <
      0.001; PDI: r = 0.67, P < 0.001) than to the objective disease severity scores
      (PASI: r = 0.34, P < 0.05). CONCLUSIONS: The QoL of partners and relatives of
      people with psoriasis can be significantly affected. Many different aspects of
      everyday life that are affected and the psychological impacts of having a partner
      or relative with psoriasis have been identified. It is of great importance to
      identify these issues to allow clinicians to develop appropriate care strategies
      not only for patients with psoriasis, but also for their partner and family.

PMID- 17459045
TI  - Indeterminate cell histiocytosis in association with later occurrence of acute
      myeloblastic leukaemia.
AB  - Indeterminate cell histiocytosis (ICH) is a proliferation of indeterminate CD1a+,
      CD68+, S100+ and CD207- dermal dendritic cells. We describe a 39-year-old man who
      developed diffuse ICH and, 6 years later, acute myeloblastic leukaemia (AML). He
      was treated with cyclophosphamide, etoposide and vinblastine until 2003. In
      August 2004, he presented dyspnoea, hyperpyrexia and infiltration of the lung
      parenchyma, compatible with an AML invasion, and died after a course of induction
      chemotherapy. Cytomorphology and immunophenotype analyses suggested an ICH clonal
      evolution. The leukaemogenic role of etoposide is discussed. ICH has previously
      been reported in association with B-cell malignancy, but only one case has shown
      systemic progression.

PMID- 17459046
TI  - Neonatal vesiculopustular eruption of the face: a sign of trisomy 21-associated
      transient myeloproliferative disorder.

PMID- 17459047
TI  - In vivo quantification of microvessels in clinically uninvolved psoriatic skin
      and in normal skin.
AB  - BACKGROUND: Microvascular abnormalities (capillary elongation, widening and
      tortuosity) are a characteristic feature of psoriasis and form one of the
      pathological diagnostic criteria. However, it is still not entirely clear when
      these microcirculatory changes appear in the skin of psoriatic subjects. Some
      studies suggest that capillary dilatation and elongation are present in the
      clinically uninvolved skin of psoriatic patients even at sites at which psoriatic
      plaques rarely occur. OBJECTIVES: To determine, using noninvasive techniques in
      vivo, the nature of any microvascular changes in the clinically uninvolved skin
      of psoriatic subjects and to quantify the dermal microvasculature in the
      clinically uninvolved skin of psoriatic subjects, in vivo. METHODS: Dermal
      microvessels in both the clinically uninvolved skin of psoriatic subjects and in
      the skin of normal volunteers (i.e. individuals without any clinical evidence of
      psoriasis or other inflammatory dermatoses) were directly visualized by native
      video-capillaroscopy, in vivo. Images were analysed using a combination of
      nonstereological and stereological measurements. The findings in each group were
      then compared to determine if there were any differences in microvascular
      parameters. RESULTS: Quantitative analysis of capillaroscopic images showed that
      there were no significant differences in microvessel density (P = 0.9), image
      area fraction (P = 0.6), microvessel length density (P = 0.7) and vessel image
      width (P = 1.0) in the clinically uninvolved skin of psoriatic subjects and the
      normal skin of healthy volunteers, when extensor forearm skin was examined.
      CONCLUSIONS: These findings indicate that prior to the development of clinical
      lesions there are no significant morphological differences between the dermal
      microvessels in the clinically uninvolved skin of psoriatic subjects and the
      dermal microvessels in the normal skin of healthy volunteers. However, during
      plaque formation, the superficial papillary microvessels in plaque skin undergo a
      striking, characteristic change, i.e. elongation, widening and tortuosity. These
      blood vessels must therefore, at least in part, play an important, necessary, but
      probably secondary role in the pathogenesis of clinical lesions in psoriasis.

PMID- 17459048
TI  - Cyclooxygenase-1 inhibition delays recovery of the cutaneous barrier disruption
      caused by mechanical scratching in mice.
AB  - BACKGROUND: Atopic dermatitis is a chronic inflammatory disease characterized by
      severe pruritus, and cutaneous barrier disruption by scratching contributes to
      further aggravation of the condition. We have previously shown that indomethacin
      delayed recovery from the effects of cutaneous barrier disruption caused by
      mechanical scratching in mice. OBJECTIVES: This study was designed to assess the
      role of cyclooxygenase (COX)-1 and COX-2 inhibitors on recovery from the effects
      of cutaneous barrier disruption induced by mechanical scratching in mice.
      METHODS: We examined the effects of SC-560 (a COX-1-selective inhibitor) or NS
      398 (a COX-2-selective inhibitor) on recovery from the effects of cutaneous
      barrier disruption in mice induced by a wire brush, in terms of the skin
      prostaglandin (PG) levels. RESULTS: While SC-560 significantly delayed recovery
      from the effects of cutaneous barrier disruption, NS-398 had no such effect. SC
      560 was significantly more effective than NS-398 in reducing skin PG levels at 6
      and 24 h after cutaneous barrier disruption. SC-560 strongly inhibited
      biosynthesis of cutaneous PGD(2) to a greater extent than that of other PGs.
      CONCLUSIONS: COX-1-coupled PGD(2) biosynthesis may be an important factor in the
      recovery of cutaneous barrier disruption.

PMID- 17459049
TI  - G-CSF is not necessary to maintain over 99% dose-intensity with ABVD in the
      treatment of Hodgkin lymphoma: low toxicity and excellent outcomes in a 10-year
      analysis.
AB  - Dose-intensity of chemotherapy is important in the treatment of Hodgkin lymphoma
      (HL) and granulocyte-colony stimulating factor (G-CSF) is commonly used to
      maintain it. We reviewed all newly diagnosed HL patients who were treated at our
      institution between 1996 and 2005. Fifty-nine patients received adriamycin,
      bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy with no dose
      reductions, treatment delays, and without G-CSF, regardless of absolute
      neutrophil count (ANC). The median ANC on all ABVD treatment days (n = 658) was
      0.925 x 10(9)/l, and was <0.5 x 10(9)/l on 26% of treatment days. Median
      normalised ABVD dose-intensity was 99.1% (range, 93-100%) and median cycle
      duration was 28.2 d. Incidence of bleomycin lung toxicity was 1.6%, 0.44%
      treatments were complicated by febrile neutropenia, and no secondary malignancies
      have occurred (median follow-up 48 months; range, 11-130 months). Five-year event
      free (EFS) and overall survival (OS) were 92.9% and 97.4% respectively.
      Furthermore, the 5-year EFS and OS (87.4% and 94.1% respectively) for advanced
      stage patients compared favourably with a similar ABVD patient group who received
      routine prophylactic G-CSF (n = 23) with EFS 80.0% and OS 91.3% (P = 0.46 and
      0.67 respectively). Our experience suggests that ABVD may be safely and
      effectively administered at >99% dose-intensity without G-CSF support, regardless
      of the ANC.

PMID- 17459050
TI  - Matched-related donor transplantation for sickle cell disease: report from the
      Center for International Blood and Transplant Research.
AB  - We report outcomes after myeloablative haematopoietic cell transplantation (HCT)
      from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with
      sickle cell disease transplanted between 1989 and 2002. The most common
      indications for transplantation were stroke and recurrent vaso-occlusive crisis
      in 38% and 37% of patients respectively. The median age at transplantation was 10
      years and 67% of patients had received >10 red blood cell transfusions before
      HCT. Twenty-seven percent of patients had a poor performance score at
      transplantation. Ninety-four percent received busulfan and cyclophosphamide
      containing conditioning regimens and bone marrow was the predominant source of
      donor cells. Most patients achieved haematopoietic recovery and no deaths
      occurred during the early post-transplant period. Rates of acute and chronic
      graft-versus-host disease were 10% and 22% respectively. Sixty-four of 67
      patients are alive with 5-year probabilities of disease-free and overall survival
      of 85% and 97% respectively. Nine patients had graft failure with recovery of
      sickle erythropoiesis, eight of who had recurrent sickle-related events. This
      report confirms and extends earlier reports that HCT from HLA-matched related
      donors offers a very high survival rate, with few transplant-related
      complications and the elimination of sickle-related complications in the majority
      of patients who undergo this therapy.

PMID- 17459051
TI  - Impact of imatinib therapy on the use of allogeneic haematopoietic progenitor
      cell transplantation for the treatment of chronic myeloid leukaemia.
AB  - The discovery and approval of imatinib drastically changed the therapeutic
      algorithm for chronic myeloid leukaemia (CML). Imatinib is now considered the
      therapy of choice for patients with newly diagnosed CML, including those
      previously considered candidates for allogeneic haematopoietic cell
      transplantation (HCT). We compared numbers and types of allogeneic HCTs performed
      for CML in North America before and after the introduction of imatinib, and
      publication of the International Randomized Trial of Interferon and STI571 (IRIS)
      using transplants reported to the Center for International Blood and Marrow
      Transplant Research (CIBMTR). The number of HCTs for CML registered with the
      CIBMTR in 1998 was 617; 62% were performed in first chronic phase (CP1). Only 1%
      of patients had received imatinib prior to transplantation. In 2003, the number
      of HCTs reported was 223; 44% were performed in CP1 and 77% of patients received
      imatinib prior to transplantation. The introduction of imatinib therapy has had a
      profound impact on the use of allogeneic transplantation for CML, with a marked
      decrease in the number of transplants for CML and an accompanying decrease in the
      proportion done in CP1. Most patients now receive a trial of imatinib before
      proceeding to HCT.

PMID- 17459052
TI  - Association of KLK5 overexpression with invasiveness of urinary bladder carcinoma
      cells.
AB  - Array-based comparative genomic hybridization (array-CGH) has powerful potential
      for high-throughput identification of genetic aberrations in cell genomes. We
      identified high-level amplification of kallikrein (KLK) genes, which are mapped
      to 19q13.3 and belong to the serine protease family, in the course of a program
      to screen a panel of urinary bladder carcinoma cell lines for genomic copy number
      aberrations using our in-house CGH-array. Expression levels of KLK5, -6, -8 and 
      9 were significantly increased in three cell lines with copy number gains of
      these KLK genes. Knockdown of these KLK transcripts by specific small interfering
      RNA significantly inhibited the invasion of a bladder carcinoma cell line through
      Matrigel in vitro. Reverse transcription-polymerase chain reaction analysis of 42
      primary bladder tumor samples showed that increased expression of KLK5 was
      frequently observed in invasive tumors (pT2-pT4) (14.3%, 6/42) compared with
      superficial tumors (pTa, pT1) (0%, 0/42; P = 0.0052), and expression levels of
      KLK5, -6, -8 and -9 mRNA were higher in invasive tumors than in superficial
      tumors (P < 0.0001, P = 0.0043, P = 0.0790 and P = 0.0037, respectively). These
      observations indicate that KLK5, -6, -8 and -9 may be the most likely targets of
      the 19q13.3 amplification, and may play a crucial role in promoting cancer-cell
      invasion in bladder tumor.

PMID- 17459053
TI  - Occludin-mediated premature senescence is a fail-safe mechanism against
      tumorigenesis in breast carcinoma cells.
AB  - We have previously demonstrated that epigenetic silencing of occludin, a tight
      junction-associated membrane protein, results in the acquisition of apoptotic
      resistance to various apoptogenic stimuli, causally contributing to the enhanced
      tumorigenicity of cancer cells. However, it remains to be examined whether
      occludin expression in transformed cells has an alternative impact that is
      important for cancer progression. Here we show that forced expression of occludin
      induces anoikis and promotes oxidative stress-induced premature senescence in
      breast carcinoma cells, which is accompanied by upregulation of negative cell
      cycle regulators such as p16(INK4A), p21(Waf1/Cip1) and p27(Kip1) but not p53.
      The senescent phenotype is reversed by specific inhibition of mitogen-activated
      protein kinase. Endogenous reexpression of occludin mediated by a synergistic
      effect with a demethylator and histone deacetylase inhibitor or retinoids that
      stimulate retinoic acid receptor alpha is also sufficient for provoking the
      senescent phenotype. In addition, tumors that developed from occludin-expressing
      cells in mice showed a feature of cellular senescence that has not been described
      as a consequence of occludin signaling. These findings suggest that the loss of
      occludin expression is at least partially involved in the senescence-escape
      program during mammary tumorigenesis.

PMID- 17459054
TI  - c-Met activation in lung adenocarcinoma tissues: an immunohistochemical analysis.
AB  - c-Met is often overexpressed in non-small cell lung cancer, but it remains
      unsolved whether its overexpression leads to its activation. We used an antibody
      specific to phospho-c-Met (Tyr1235) to investigate c-Met activation
      immunohistochemically in 130 surgically resected lung adenocarcinomas. The
      expression of c-Met and hepatocyte growth factor (HGF) was also investigated.
      Phospho-c-Met was positive in 21.5% (28/130) of cases. c-Met was positive in
      74.6% of cases (97/130) and was expressed at high levels in 36.1% of cases
      (47/130). HGF was expressed at high levels in 31.5% of cases (41/130). Phospho-c
      Met was correlated with high levels of HGF (P =0.0010) and high levels c-Met
      expression (P = 0.0303), but it was also found to be positive in 12 cases with
      little to no HGF expression. Phospho-c-Met expression was significantly
      associated with tumor differentiation (P = 0.0023) and papillary histology (P =
      0.0011), but not with pathological stage, lymph node metastasis or survival. High
      levels of c-Met and HGF were also associated with papillary histology (P = 0.0056
      and P = 0.0396, respectively), but not with tumor differentiation. Phospho-c-Met
      was correlated with phospho-Akt (P = 0.0381), but not with phospho-Erk or phospho
      Stat3. Phospho-Akt expression was marginally correlated with the expression of
      phospho-epidermal growth factor receptor (EGFR) (P = 0.0533) and, importantly, it
      was strongly correlated with the expression of either phospho-c-Met or phospho
      EGFR (P = 0.0013). The data suggest that in lung adenocarcinoma tissue, c-Met
      activation may take place either ligand-dependently or ligand-independently via c
      Met overexpression. c-Met activation may play special roles in the papillary
      subtype and in well differentiated lung adenocarcinomas.

PMID- 17459055
TI  - Prognostic implications of the nuclear localization of Y-box-binding protein-1
      and CXCR4 expression in ovarian cancer: their correlation with activated Akt,
      LRP/MVP and P-glycoprotein expression.
AB  - The nuclear localization of Y-box-binding protein-1 (YB-1) is known to be a poor
      prognostic factor in several human malignancies, including ovarian carcinoma.
      Following on from our basic study dealing with microarray analyses of YB-1
      associated gene expression in ovarian cancer cells, we examined whether nuclear
      localization of YB-1 is associated with the expression of CXCR4, a vault protein
      named lung resistance-related vault protein (LRP/MVP), phosphorylated Akt (p-Akt)
      or P-glycoprotein (P-gp) in human ovarian carcinoma. Fifty-three surgically
      resected ovarian carcinomas treated with paclitaxel and carboplatin were examined
      immunohistochemically for nuclear YB-1 expression and intrinsic expression of p
      Akt, P-gp, LRP/MVP and CXCR4. Nuclear expression of YB-1 demonstrated significant
      correlation with p-Akt, P-gp and LRP expression, but no relationship with CXCR4
      expression. By multivariate analysis, only YB-1 nuclear expression and CXCR4
      expression were independent prognostic factors with regard to overall survival.
      These results indicate that YB-1 nuclear expression and CXCR4 expression are
      important prognostic factors in ovarian carcinoma.

PMID- 17459056
TI  - BCL2L2 is a probable target for novel 14q11.2 amplification detected in a non
      small cell lung cancer cell line.
AB  - Amplification of chromosomal DNA is thought to be one of the mechanisms that
      activates cancer-related genes in tumors. In a previous genome-wide screening of
      DNA copy number aberrations in a panel of non-small cell lung cancer (NSCLC) cell
      lines using an in-house bacterial artificial chromosome-based array, we
      identified a novel amplification at 14q11.2 in HUT29 cells derived from human
      lung adenocarcinoma. To identify the most likely target for the 14q11.2
      amplification, we determined the extent of the amplicon by fluorescence in situ
      hybridization and then analyzed NSCLC cell lines for the expression levels of 28
      genes present within the 1-Mb amplified region. Significant overexpression in the
      HUT29 cell line with amplification, relatively frequent overexpression in
      additional NSCLC cell lines compared with an immortalized normal lung epithelial
      cell line, and reported information about the function of each candidate gene
      prompted us to characterize the BCL2-like2 (BCL2L2) gene, a prosurvival member of
      the BCL2 family, as the most likely target for the 14q11.2 amplicon.
      Immunohistochemical analysis of 61 primary cases of lung adenocarcinoma
      demonstrated that BCL2L2 overexpression was significantly associated with tumor
      stage and differentiation status, and tended to be associated with a poorer
      prognosis. Downregulation of BCL2L2 expression using small interfering RNA
      dramatically inhibited the growth of HUT29 cells, but showed no effect on
      anticancer reagent-induced cell death of the same cell line. These findings
      demonstrate that overexpressed BCL2L2, through amplification or other mechanisms,
      promotes the growth of NSCLC, especially the adenocarcinoma subtype, and might be
      a therapeutic target.

PMID- 17459057
TI  - Gastric and intestinal claudin expression at the invasive front of gastric
      carcinoma.
AB  - Like gastric and intestinal mucins, the tight junction proteins called claudins
      can be used to determine the differentiation of gastric mucosa. We investigated
      the expression of claudins in gastric cancer and proposed a new claudin-based
      gastric cancer classification system. The expression of gastric (claudin-18) and
      intestinal (claudin-3 and claudin-4) claudins in non-neoplastic gastric mucosa
      (with intestinal metatplasia [IM], 78 cases; without IM, 88 cases) and 94 gastric
      cancers was analyzed immunohistochemically, as was the expression of gastric
      (MUC5A and MUC6) and intestinal (CD10 and MUC2) mucins. Heterogeneous expression
      of claudin-3, claudin-4 and claudin-18 was detected in advanced gastric cancer;
      however, there was no significant association between the claudins and the
      clinicopathological parameters. These gastric cancer tissues were also
      subclassified into claudin-based phenotypes: gastric claudin (G-CLDN), 28 cases
      (30%); intestinal claudin (I-CLDN), 41 cases (44%); and unclassified claudin (U
      CLDN), 25 cases (26%). Interestingly, the U-CLDN gastric cancers had worse
      malignancy grades, not only in size and invasiveness but also in potential
      metastatic ability and patient outcome. Although the mucin-based gastric cancer
      classification was also assessed, no significant correlation was found between
      mucin production and clinicopathological parameters. These observations suggest
      that loss of claudin expression may enhance the grade of malignancy of gastric
      cancer in vivo. Classification of gastric cancers using gastric and intestinal
      claudins is a good biomarker for assessing the risk of poor prognosis.

PMID- 17459058
TI  - Correlation between liver metastasis of the colocalization of actin-related
      protein 2 and 3 complex and WAVE2 in colorectal carcinoma.
AB  - Directed movement of normal cells occurs when actin-related protein 2 and 3
      complex (Arp2/3 complex) triggers the actin polymerization that forms
      lamellipodia immediately after binding to WAVE2. In order to determine whether
      the same mechanism correlates with liver metastasis from colorectal cancer,
      paired mirror sections of 154 cancer specimens (29 cases with liver metastasis
      and 125 cases without liver metastasis in which T factor, gender, primary tumor
      site, and age at operation were matched) were examined immunohistochemically for
      the localization of Arp2 and WAVE2. Expression of both Arp2 and WAVE2 was
      detected in the same cancer cells in 55 (35.7%) of the 154 cases, but not
      detected in the normal colonic epithelial cells. Univariate analysis showed that
      the colocalization was significantly predictive of liver metastasis (risk ratio
      [RR] 8.760. Likewise, histological grade (RR 2.46), lymphatic invasion (RR 9.95),
      and tumor budding (RR 4.00) were significant predictors. Among these,
      colocalization and lymphatic invasion were shown to be independent risk factors
      by multivariate analysis. Another 59 colorectal specimens were examined for mRNA
      expression of Arp2 by real time polymerase chain reaction. High mRNA levels of
      Arp2, that in situ hybridization revealed to be expressed by the cancer cells,
      were significantly associated with liver metastasis. However, its effect was
      absorbed by the influence of risk of the colocalization that is closely related
      to high expression of Arp2. These results indicate that the colocalization of
      Arp2 and WAVE2 is an independent risk factor for liver metastasis of colorectal
      carcinoma.

PMID- 17459059
TI  - Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer
      through its specific membrane receptors AdipoR1 and AdipoR2.
AB  - Adiponectin, a circulating peptide hormone produced in adipose tissue, has been
      shown to be reduced in the plasma of patients with cancer, suggesting that this
      adipokine may be mechanically involved in the pathogenesis of adiposity-related
      carcinogenesis. In this study, we examined the expression of adiponectin
      receptors (AdipoR1 and AdipoR2) and assessed the function of adiponectin in
      gastric cancer. All of the six gastric cancer cell lines significantly expressed
      mRNA and protein of both receptors with variable levels. Addition of 30 microg/mL
      adiponectin potently induced apoptosis and inhibited the proliferation of AZ521
      and HCG27. Down-regulation of either AdipoR1 or AdipoR2 by specific siRNA
      significantly suppressed the growth inhibitory effects of adiponectin in both
      cell lines. Moreover, a local injection of adiponectin markedly inhibited the
      growth of AZ521 inoculated subcutaneously in nude mice. Similarly, the continuous
      intraperitoneal infusion of adiponectin effectively suppressed the development of
      peritoneal metastasis of AZ521. Adiponectin negatively regulates the progression
      of gastric cancer cells possibly through both AdipoR1 and AdipoR2. Although
      adiponectin was already reported to have antiangiogenic effects, our results
      suggest that the antitumor effect of adiponectin was, at least partially,
      dependent on the direct effects on tumor cells.

PMID- 17459060
TI  - RNA interference-mediated signal transducers and activators of transcription 3
      gene silencing inhibits invasion and metastasis of human pancreatic cancer cells.
AB  - Signal transducers and activators of transcription-3 (STAT3), a central
      cytoplasmic transcription factor, is frequently overexpressed and constitutively
      activated by tyrosine during malignant transformation. The overexpression and
      phosphorylation of STAT3 in pancreatic cancer has been described only recently,
      but the roles and mechanism still remain unclear. In this study, we elucidate the
      significance of the STAT3 signaling pathway in metastatic potentials of
      pancreatic cancer. We stably silence the expression of the STAT3 and p-STAT3 by
      using RNA interference (RNAi) in the pancreatic cancer cell line SW1990, and then
      reduce its invasion capacity in vitro and metastasis capacity in vivo compared to
      parental cells or cells tansfected with a control vector. Furthermore, silencing
      SW1990 cells with the STAT3 gene by RNAi also led to a decrease of matrix
      metalloproteinases-2 (MMP-2) and vascular endothelial growth factor (VEGF) at the
      mRNA and protein level. Collectively, these studies suggest that activation of
      the STAT3 signaling pathway plays an important role in the progression of
      pancreatic cancer, and that silence of the STAT3 gene with RNAi may be a useful
      anti-invasive therapeutic option in pancreatic cancer.

PMID- 17459061
TI  - Changes in the invasive and metastatic capacities of HT-29/M3 cells induced by
      the expression of fucosyltransferase 1.
AB  - Lewis antigens are terminal fucosylated oligosaccharides synthesized by the
      sequential action of several glycosyltransferases. The fucosyltransferases are
      the enzymes responsible for the addition of terminal fucose to precursor
      oligosaccharides attached to proteins or lipids. These oligosaccharides, defined
      as cell surface markers, have been implicated in different types of intercellular
      interactions and in adhesion and invasion processes. Transfection of HT-29/M3
      colon cancer cells with the full length of human fucosyltransferase (FUT1),
      induces the synthesis of H type 2 and Lewis y antigens, associated with a
      decrease of sialyl-Lewis x. The capacity to develop primary tumors when cells
      were injected intrasplenically was similar in parental and FUT1-transfected
      cells, but the capacity to colonize the liver after spleen removal was
      significantly reduced in M3/FUT1 transfected cells. These results indicate that
      the expression of FUT1 induces changes in the metastatic capacity of HT-29/M3
      colon cancer cells, as a consequence of the altered expression pattern of type 2
      Lewis antigens. Also, an association between MUC5AC expression and the degree of
      gland differentiation in both primary splenic tumors and hepatic metastases was
      detected.

PMID- 17459062
TI  - Gene expression profiling of epidermal growth factor receptor/KRAS pathway
      activation in lung adenocarcinoma.
AB  - We examined the genome-wide expression profiles of 86 primary lung
      adenocarcinomas and compared them with the mutation status of the four key
      molecules (EGFR, ERBB2, KRAS and BRAF) in the EGFR/KRAS/BRAF pathway.
      Unsupervised classification revealed two subtypes (the bronchial type and the
      alveolar type) of lung adenocarcinoma. Mutually exclusive somatic mutations of
      the epidermal growth factor receptor (EGFR) gene (36/86, 41.8%), K-ras gene
      (11/86, 12.8%) and BRAF gene (1/86, 1.1%) were detected. KRAS mutations were
      observed significantly frequently in bronchial-type tumors, whereas the
      frequencies of EGFR mutations were similar in both the alveolar and bronchial
      types. Twenty-seven genes showed increased expression in EGFR-mutated tumors and
      these included molecules that function in the EGFR/KRAS/BRAF pathway (EGFR, AKT1
      and BCR). In particular, expression of BCR, which is required for EGFR protein
      degradation, was induced by EGF stimulation, suggesting a negative feedback loop
      in lung cancer. A subgroup of the alveolar type tumors showed significantly
      better prognosis than other tumors. Integrated analysis of genetic and gene
      expression profiling aimed to delineate inherent oncogenic pathways in cancer
      will be valuable not only for the understanding of molecular pathogenesis, but
      also for discovering novel biomarkers and predicting clinical outcome.

PMID- 17459063
TI  - Immunological evaluation of personalized peptide vaccination in combination with
      a 5-fluorouracil derivative (TS-1) for advanced gastric or colorectal carcinoma
      patients.
AB  - The aim of the present study was to investigate the safety and immunological
      responses of personalized peptide vaccination in combination with oral
      administration of a 5-fluorouracil derivative (TS-1) in advanced gastric or
      colorectal carcinoma patients. Eleven patients (four with gastric cancer and
      seven with colorectal cancer) who failed to improve by prior TS-1-based
      chemotherapies were enrolled in this study. Peptides to be administered to
      patients were determined based on the presence of peptide-specific cytotoxic T
      lymphocyte (CTL) precursors in peripheral blood mononuclear cells and peptide
      specific IgG in the plasma of cancer patients. Patients were vaccinated with
      peptides (a maximum of four) biweekly in combination with or without three
      different doses of TS-1 (20, 40 and 80 mg/m(2)/day). Although grade 3 toxicity,
      including anemia (one patient) and neutropenia (one patient) were observed, the
      combination therapy was generally well tolerated. An increase in peptide-specific
      IgG after the sixth vaccination was observed in the vast majority of patients
      irrespective of the dose of TS-1 used. In contrast, an increase in peptide
      specific interferon-gamma production by CTL was most evident in patients who were
      administered the highest dose of TS-1. Furthermore, in the patients who received
      80 mg/m(2)/day TS-1, CTL-mediated cytotoxicity against cancer cells was
      maintained at the prevaccination level. These results indicate that
      administration of the standard dose (80 mg/m(2)/day) of TS-1 in combination with
      a personalized peptide vaccination does not necessarily impede immunological
      responses in cancer patients, and could actually maintain or augment them.

PMID- 17459064
TI  - Can targeted intervention in CRC patients' relatives influence screening
      behaviour? A pilot study.
AB  - OBJECTIVE: This study aimed to assess the utility of a standardised risk
      information tool with respect to the uptake of screening activities administered
      to an accessible population of first-degree relatives of patients with sporadic
      colorectal cancer. METHOD: Patients admitted for colorectal cancer resection were
      invited to enroll their family unit in the study. Families were randomised either
      to receive standard care or the intervention tool. The intervention group
      received a structured one page pamphlet outlining the risk associated with a
      family history of colorectal cancer, and the availability of and potential
      benefits from screening. Three months after the initial contact with the index
      patient, family members were invited to participate in a telephone interview.
      Primary end-points were both intention to screen and uptake of screening
      activities. RESULTS: Forty-seven families had 156 eligible first degree
      relatives. Ninety-one consented to participate and were enrolled: 59 received
      standard care, 32 received the intervention. Age and sex were similar between
      groups. There was no significant difference in previous screening activities. The
      intervention tool had no influence on perceived self-risk of developing
      colorectal cancer or uptake of screening activities within the study period.
      CONCLUSION: This study suggests that the provision of targeted risk information
      to first-degree relatives is not likely to positively influence screening
      behaviour. Health care providers need to find alternative methods of
      disseminating information to this high-risk group.

PMID- 17459065
TI  - Lipid peroxidation and antioxidant status in lichen planus.
AB  - BACKGROUND: Lichen planus (LP) is an inflammatory skin disease of unknown
      aetiology. Recently, increased oxidative stress has been implicated in the
      pathogenesis of various skin diseases such as atopic dermatitis, psoriasis
      vulgaris and vitiligo. AIM: To evaluate the status of the oxidative stress and
      antioxidant defence system in patients with LP. METHODS: In total, 40 patients
      with LP (23 men, 17 women; mean +/- SD age 43.27 +/- 1.96 years) and 40 control
      subjects, matched for age and gender, were enrolled in this prospective study.
      The exclusion criteria included medication with immunosuppressive agents, history
      of trauma and surgery, and history of alcohol ingestion for at least 1 month
      prior to the study. The serum nitric oxide (NO), malondialdehyde (MDA) and
      superoxide dismutase (SOD) levels and the erythrocyte catalase (CAT) levels were
      investigated in both groups. RESULTS: Mean +/- SD levels of serum NO (74.60 +/-
      17.96 micromol/L) and MDA (18.24 +/- 5.21 micromol/L) in patients with LP were
      higher than those of the control group (P = 0.007 and P = 0.031, respectively).
      Serum SOD levels (18.19 +/- 3.71 U/mL) in patients with LP were also higher than
      in healthy controls (P = 0.002). In contrast, erythrocyte CAT levels (13 557.80
      +/- 4134.42 U/kg haemoglobin) were significantly lower in the patient group than
      in the control group (P = 0.009). CONCLUSIONS: The findings of this study suggest
      that increased oxidative stress, increased lipid peroxidation and an imbalance in
      the antioxidant defence system may be involved in the pathogenesis of LP.

PMID- 17459066
TI  - Photodetection of basal cell carcinoma using methyl 5-aminolaevulinate-induced
      protoporphyrin IX based on fluorescence image analysis.
AB  - BACKGROUND: The preferential accumulation of 5-aminolaevulinic acid (ALA)-induced
      protoporphyrin IX (PpIX) in neoplastic cells supports its potential use in the
      photodetection of porphyrin fluorescence in tumour cells. Hence, epithelial
      tumours, including basal cell carcinoma (BCC), might be visualized using the
      fluorescence of selectively accumulated ALA-induced PpIX. AIM: In this study, we
      evaluated the clinical efficacy of PpIX fluorescence images using fluorescence
      image analysis (FIA) to define the lateral border between the tumour and tumour
      free areas of facial BCC. METHODS: FIA was used to define the lateral border
      between the tumour and tumour-free areas on red fluorescence images induced by
      the topical application of methyl 5-aminolaevulinate (MAL) ointment. According to
      the FIA results, 50 tissue samples, obtained from 10 patients with BCC, were
      divided into three categories: tumour area (n = 10), suspected tumour area (n =
      20) and suspected tumour-free area (n = 20). These tissue samples were evaluated
      by histopathological examination. The FIA tool marked out the PpIX fluorescence
      image for defining the lateral border between the BCC tumour and tumour-free
      areas. RESULTS: The rate of tumour detection from BCC lesions using PpIX
      fluorescence with the FIA tool showed a sensitivity of 94.1% and specificity of
      82.6%. CONCLUSION: These results suggest that MAL-induced PpIX fluorescence
      imaging using FIA is quite sensitive and specific for detecting tumour and occult
      tumour in facial BCC lesions. This method of presurgical in vivo imaging is
      therefore proposed as a useful tool for defining the lateral border between BCC
      tumour and tumour-free areas.

PMID- 17459067
TI  - Leprosy-associated eccrine syringofibroadenoma of Mascaro.
AB  - Eccrine syringofibroadenoma of Mascaro is a rare benign tumour. There are five
      subtypes, one of which is known to occur in reaction to inflammatory and
      neoplastic dermatoses. We describe a patient with previous lepromatous leprosy
      presenting with multiple flesh-coloured verrucous plaques over the right foot.
      Histology was consistent with eccrine syringofibroadenoma. To our knowledge, this
      is the first reported case of multiple eccrine syringofibroadenomata occurring in
      association with leprosy. The tumours in this case are most likely reactive in
      nature, subsequent to multiple traumatic events with tissue remodelling in an
      insensate foot affected by leprosy. It is less probable that the tumours are a
      result of scarring from recurrent infections. We also raise the possibility of a
      neuroeccrine interaction, with sympathetic neuropathy in leprosy as a
      contributing factor in the pathogenesis.

PMID- 17459068
TI  - Ulcerated sclerotic giant congenital melanocytic naevus: case report and review
      of the literature.
AB  - We report a case of a white girl with an ulcerated giant congenital melanocytic
      naevus that initially had a hard, stony consistency but in which the pigmentation
      and the induration are progressively vanishing. Very few cases of this variant of
      GCMN, known as sclerodermoid GCMN or desmoplastic hypopigmented hairless naevus,
      have been reported to date, and clinical evolution seems to be heterogeneous. We
      review the published cases and propose the term 'sclerotic hypopigmented GCMN as
      a common descriptor of this type of congenital melanocytic naevus.

PMID- 17459069
TI  - Hutchinson-Gilford progeria syndrome with severe skin calcinosis.
AB  - We describe a case of Hutchinson-Gilford progeria syndrome (HGPS) with long-term
      follow-up. A 1-month-old girl with marked sclerodermatous skin changes developed
      various symptoms of HGPS during follow-up. These included sclerotic skin,
      pigmentation, skin atrophy with translucent veins, wispy hair and alopecia, nail
      dystrophy and decreased sweating. Marked skin calcinosis was observed over almost
      the entire body, a symptom that has apparently been ignored in the literature. At
      16 years old, the girl underwent surgery for a skull fracture and subdural
      haematoma, which was followed by chronic ulceration. Wet dressing with insulin
      like growth factor was used with considerable effect. Mutation of the lamin A/C
      (LMNA) gene mutation, which encodes nuclear lamin A and C, has been reported to
      be the cause of HGPS. Our case showed the mutation G608G (GGC-->GGT), which
      resulted in a cryptic splice site and consequently in a truncated lamin A/C
      protein.

PMID- 17459070
TI  - Congenital desmoplastic trichoepithelioma.
AB  - Desmoplastic trichoepithelioma (DT) is a rare benign adnexal neoplasm considered
      to have follicular differentiation. It usually presents as an asymptomatic, firm,
      annular plaque with a raised border. The most common site of occurrence is the
      face, usually on the cheek. Females are more often affected than males and the
      age range of patients previously reported is 8-79 years. We present a case of
      congenital desmoplastic trichoepithelioma. A girl was born at term to a healthy
      mother after an uneventful pregnancy and was noted to have widespread
      erythematous plaques with milia-like lesions over the right scalp, face and neck,
      with some areas of atrophic scarring. Histology and immunohistochemistry of
      incisional biopsies of the lesions were consistent with a diagnosis of DT. To our
      knowledge, this is the first reported case of congenital DT.

PMID- 17459071
TI  - Epidermolysis bullosa acquisita associated with psoriasis vulgaris.
AB  - We report a case of epidermolysis bullosa acquisita (EBA) associated with
      psoriasis vulgaris. A 71-year-old woman with psoriasis vulgaris developed
      subepidermal blisters on the extremities. Direct immunofluorescence demonstrated
      linear deposit of IgG at the basement membrane zone, which bound to the dermal
      side of normal human skin split with 1 mol/L NaCl. Immunoblot analysis using
      recombinant full-length type VII collagen detected a 290-kDa band, confirming the
      diagnosis of EBA. A literature search for previous reports found a few cases of
      EBA associated with psoriasis, and all cases, including our own, presented with
      widespread inflammatory vesicles and bullae, and responded to conventional
      therapy with corticosteroids and immunosuppressive agents. This study suggests
      that western blotting using recombinant full-length type VII collagen could be
      useful for diagnosis of EBA, and that EBA associated with psoriasis may have a
      tendency to be the inflammatory type.

PMID- 17459072
TI  - Dermal-binding linear IgA disease: an uncommon subset of a rare immunobullous
      disease.
AB  - BACKGROUND: Linear IgA disease (LAD) is an acquired subepidermal blistering
      disorder, characterized clinically by urticated plaques, papules, vesicles and
      bullae. Scarring is not usually observed. Direct immunofluorescence on clinically
      uninvolved skin shows linear deposition of IgA at the basement membrane zone
      (BMZ). Indirect immunofluorescence on salt-split skin shows dermal binding in a
      minority of cases. AIM: To identify and characterize patients with LAD who have
      IgA anti-BMZ autoantibodies directed against the dermal side of salt-split human
      skin (dermal-binding autoantibodies). METHODS: This was a retrospective study of
      patients with a diagnosis of LAD referred to the dermatology department in Oxford
      between 1986 and 2004, who demonstrated dermal-binding circulating IgA
      autoantibodies on indirect immunofluorescence. Clinical features were reviewed
      and target antigens identified by immunoblotting. RESULTS: In total, 17 of 101
      patients with LAD were found to have dermal-binding autoantibodies. This subset
      of LAD was relatively more common in adults than in children. There were no other
      clinical features that distinguished these patients from others with LAD.
      Collagen VII, the target antigen in epidermolysis bullosa acquisita (EBA), was
      identified in two of our cohort, but none of the classic clinical features of
      mechanobullous EBA was observed. CONCLUSION: This is the largest cohort of
      patients with dermal-binding LAD to date. Our patients were clinically
      indistinguishable from those with non dermal-binding LAD, and showed no evidence
      of the classic mechanobullous EBA phenotype.

PMID- 17459073
TI  - Does hair prevent acne? Insights from alopecia areata.

PMID- 17459074
TI  - Subacute cutaneous lupus erythematosus presenting as erythroderma.
AB  - Erythrodema secondary to subacute cutaneous lupus erythematosus (SCLE) is rare.
      We report a 61-year-old man presenting with erythroderma secondary to SCLE.
      During erythrodermic phase our patient still had few annular and polycyclic
      lesions characteristic of SCLE. He was successfully treated with topical and oral
      corticosteriods.

PMID- 17459075
TI  - Association of -318 C/T and +49 A/G cytotoxic T lymphocyte antigen-4 (CTLA-4)
      gene polymorphisms with a clinical subset of Italian patients with systemic
      sclerosis.
AB  - Systemic sclerosis (SSc) is a complex and heterogeneous autoimmune disorder with
      a multi-factorial pathogenesis. Like other autoimmune disorders, the possible
      role of specific cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms in
      predisposing to SSc has been hypothesized, but it remains controversial. CTLA-4
      promoter (-318C/T) and exon 1 (+49 A/G) polymorphisms have been analysed in 43
      Italian females with SSc and in 93 unrelated matched healthy controls by a newly
      designed tetra-primer amplification refractory mutation system-polymerase chain
      reaction (T-ARMS-PCR) method. No significant association has been found with
      either polymorphisms.Nevertheless, SSc patients without concomitant Hashimoto's
      thyroiditis (HT) were carrying both the -318T allele (P = 0.031) and the +49 G
      allele (P = 0.076) more frequently than SSc patients with HT [defined by
      positivity for anti-thyroperoxidase (TPO) and anti-thyroglobulin (TGA)
      autoantibodies] than controls. Haplotype analysis confirms this association (P =
      0.028), and suggests the predominant role of the -318T, whereas that of the +49
      G, if any, seems weak. Thus, in Italian SSc patients the CTLA-4 -318C/T promoter
      polymorphism appears to be associated with the susceptibility to develop SSc
      without thyroid involvement. Larger studies are needed to confirm these findings
      and to clarify whether the -318C/T polymorphism is the functional responsible or
      whether it reflects the presence of another linked genetic element in the same
      chromosomal region.

PMID- 17459076
TI  - Selective unresponsiveness to beta cell autoantigens after induction
      immunosuppression in pancreas transplantation with anti-interleukin-2 receptor
      antibody versus anti-thymocyte globulin.
AB  - Pancreas transplantation in type 1 diabetes patients could result in
      (re)activation of allo- and autoreactive T lymphocytes. Anti-thymocyte globulin
      (ATG) induction treatment is a successful, but broadly reactive anti-lymphocyte
      therapy used in pancreas and islet transplantation. A more selective alternative
      is daclizumab, a monoclonal antibody directed against the interleukin-2 receptor
      (CD25) on activated lymphocytes. We tested the hypothesis that daclizumab is more
      selective and has less immunological side effects than ATG. Thirty-nine
      simultaneous pancreas-kidney transplantation patients with type 1 diabetes were
      randomized for induction therapy with ATG or daclizumab. Auto- and recall
      immunity was measured cross-sectionally by lymphocyte stimulation tests with a
      series of auto- and recall antigens in 35 successfully transplanted patients. T
      cell autoimmunity to islets was low in both groups, except for a marginal but
      significantly higher reactivity against glutamic acid decarboxylase (GAD)65 in
      daclizumab-treated patients. The memory responses to recall antigens were
      significantly higher in the daclizumab-treated group compared to ATG-treated
      patients, specifically against purified protein derivative (PPD) (anti-bacterial
      immunity), Haemophilus influenzae virus matrix protein-1 (anti-viral immunity)
      and p53 [anti-tumour (auto)immunity]. These data imply that daclizumab is more
      specifically affecting diabetes-related immune responses than ATG. The
      autoimmunity is affected effectively after daclizumab induction, while memory
      responses towards bacterial, viral and tumour antigens are preserved.

PMID- 17459077
TI  - CXC chemokine ligand 16 in periodontal diseases: expression in diseased tissues
      and production by cytokine-stimulated human gingival fibroblasts.
AB  - Periodontal disease is an inflammatory disorder characterized by the involvement
      of chemokines that are important for the recruitment of leucocytes. Several
      cytokines are involved in regulating levels of chemokines in periodontal disease.
      CXCL16 is a chemokine related to the migration of T helper 1 (Th1) cells and
      natural killer (NK) cells. In this study, we examined its expression in
      periodontal tissues. Moreover, we investigated the effects of cytokines on the
      production of CXCL16 by human gingival fibroblast (HGF). Reverse transcription
      polymerase chain reaction (RT-PCR) analysis and immunohistochemistry revealed
      that CXCL16 and its receptor, CXCR6, were expressed at the mRNA and protein
      levels in diseased tissues. Proinflammatory cytokines [interleukin (IL)-1beta,
      tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma] increased the mRNA
      expression and release of CXCL16 in a dose-dependent manner. Moreover, treatment
      of HGFs with IFN-gamma in combination with IL-1beta had a synergistic effect on
      the production of CXCL16. On the other hand, IL-4 and IL-13 inhibited the IL
      1beta-induced CXCL16 production by HGFs. Inhibitors of A disintegrin and
      metalloprotease (ADAM)10 and ADAM17, a recently identified protease of CXCL16,
      reduced the amount of CXCL16 released from HGFs. These results suggest that the
      CXCL16 produced by HGFs may be involved in the migration of leucocytes into
      inflamed tissues, and provide evidence that CXCL16 production is controlled by
      cytokines in periodontal disease.

PMID- 17459078
TI  - Proportion of peripheral blood and decidual CD4(+) CD25(bright) regulatory T
      cells in pre-eclampsia.
AB  - CD4(+) CD25(bright) regulatory T (T(reg)) cells have been identified as a
      principle regulator of tolerance during pregnancy. In the setting of pre
      eclampsia, however, little is known about the dynamics of these cells. In the
      current study, we determined CD4(+) CD25(bright) T(reg) cells in the peripheral
      blood using flow cytometry and forkhead box P3 (FoxP3(+)) cells at the placental
      bed using immunohistochemical staining. Peripheral blood mononuclear cells (PBMC)
      of 38 pre-eclamptic cases (17 cases Japanese, 21 cases Polish), 40 normal late
      pregnancy subjects (20 subjects Japanese, 20 subjects Polish), and 21 non
      pregnant healthy controls (10 subjects Japanese, 11 subjects Polish) were
      included. We found the percentage of CD25(bright) cells within the CD4(+) T cell
      population in PBMC was reduced significantly in both Japanese and Polish pre
      eclamptic cases than in normal pregnancy subjects (P < 0.001) and non-pregnant
      healthy controls (P < 0.001). Also, the percentage of FoxP3(+) cells within
      CD3(+) T cells in the placental bed biopsy samples of pre-eclamptic cases were
      decreased compared to those in normal pregnancy subjects. These findings suggest
      that a decreased number of T(reg) cells was present in pre-eclampsia, and these
      changes might break the maternal tolerance to the fetus.

PMID- 17459079
TI  - Increased expression of Toll-like receptor 4 in peripheral blood leucocytes and
      serum levels of some cytokines in patients with ankylosing spondylitis.
AB  - Toll-like receptor 4 (TLR4) is a member of the Toll-like receptor family, which
      can bridge innate and adaptive immune responses. Activation of the TLR4
      signalling pathway may induce the release of proinflammatory cytokines such as
      tumour necrosis factor (TNF)-alpha and interleukin (IL)-12, which was considered
      to play an important role in pathogenesis of immune-mediated diseases. Ankylosing
      spondylitis (AS) is an immune-mediated disease whose aetiology remains unknown.
      The aim of the study was to investigate the expression of TLR4 and serum TNF
      alpha, IL-12 and soluble tumour necrosis factor-related apoptosis-inducing ligand
      (sTRAIL) level in AS patients. The results indicated that TLR4 protein and mRNA
      levels were significantly higher in AS patients than in healthy controls;
      however, there was no significant difference between human leucocyte antigen
      (HLA)-B27-positive and -negative AS patients, as well as serum levels of TNF
      alpha, IL-12 and sTRAIL. In addition, in HLA-B27-positive AS patients, TLR4 level
      showed close associations with the cytokines and laboratory parameters of disease
      activity [erythrocyte sedimentation rate (ESR) and plasma C-reactive protein
      (CRP)], respectively. Similarly, the strong associations between the cytokines or
      between IL-12 and ESR or CRP were observed in HLA-B27-positive AS patients.
      Interestingly, in HLA-B27-positive AS patients, TNF-alpha correlated
      significantly with ESR, but did not with CRP. In contrast, sTRAIL correlated with
      CRP, but did not with ESR. Among HLA-B27-negative patients, no close correlation
      was found. In our study, it was suggested that the abnormal activation of TLR4
      signalling and serum TNF-alpha, IL-12 and sTRAIL may play a key role in the
      development and progression of AS, which may be dependent on the status of HLA
      B27 antigen.

PMID- 17459080
TI  - Salmonella typhimurium stimulation combined with tumour-derived heat shock
      proteins induces potent dendritic cell anti-tumour responses in a murine model.
AB  - Appropriate activation of the immune system and effective targeting of tumour
      cells are the primary hurdles to be overcome for cancer immunotherapy to be
      successful and applicable to a wide range of tumour types. Our studies have
      examined the ability of bacterial-stimulated dendritic cells (DCs), loaded with
      tumour-associated antigens, to inhibit tumour growth in a murine model. Immature
      murine bone marrow-derived DCs were stimulated in vitro with the cytoplasmic
      fraction (CM) of Salmonella typhimurium in combination with heat shock proteins
      (hsps) from 4T1 tumours, isolated using heparin affinity chromatography.
      Activated DCs were administered subcutaneously. Tumours were generated by
      orthotopic inoculation of 4T1 cells in Balb/c mice. Primary tumour growth was
      measured using Vernier calipers, while lung metastases were measured using the
      clonogenic assay. S. typhimurium CM induced potent tumour necrosis factor (TNF)
      alpha responses from DCs accompanied by significant up-regulation of CD80 and
      CD86 expression. When injected into mice, bacterial-stimulated DCs loaded with
      4T1 hsps inhibited the formation of new 4T1 tumours and reduced the growth rate
      of established tumours. In addition, the number of lung metastatic nodules was
      reduced significantly in the DC-treated mice (1.6 +/- 0.6 versus 245.9 +/- 55.6,
      P = 0.0015). DCs stimulated with CM alone, exposed to tumour hsps alone or
      exposed to tumour hsps from an unrelated tumour cell line did not induce a
      protective immune response. Dendritic cells primed with a proinflammatory
      bacterial stimulus and tumour-associated antigens induce a protective anti-tumour
      immune response in this murine model.

PMID- 17459081
TI  - Factors associated with the prophylactic effect of placebo injections in subjects
      enrolled in a study of botulinum toxin for migraine.
AB  - We set out to identify predictors for the prophylactic effect of placebo
      injections in subjects with migraine by post hoc analysis of 81 subjects with
      episodic migraine receiving single-blind placebo injections in a prospective
      trial of botulinum toxin. Possible predictors of placebo prophylaxis were
      compared among placebo responders (PRs) and placebo non-responders (PNRs). There
      were 34 PRs (42%) and 47 PNRs (58%). Male gender [odds ratio (OR) 5.83, 95%
      confidence interval (CI) 1.12, 30.14, P = 0.022], a history of opioid use (OR
      4.44, 95% CI 1.47, 13.41, P = 0.005) and injections in the neck/shoulders (OR
      2.44, 95% CI 0.93, 3.19, P = 0.033) were associated with placebo response. Of
      subjects with two or more of these signs, 88% were PRs compared with 31% of
      subjects with one or less. Male gender, opioid use and injections in the
      neck/shoulders are associated with placebo prophylaxis. These findings may have
      important implications for the design of future clinical trials and for the
      clinical management of migraineurs.

PMID- 17459082
TI  - Migraine symptoms related to the percutaneous closure of an ostium secundum
      atrial septal defect: report of four paediatric cases and review of the
      literature.
AB  - Several publications have recently suggested that atrial septal defect may be
      associated with the physiopathology of headache with migraine-type
      characteristics. We describe four previously asymptomatic paediatric patients
      with atrial septal defect who underwent percutaneous Amplatzer septal occluder
      device implantation and who subsequently developed symptoms compatible with
      migraine headache. The cases had normal echocardiograms after the intervention
      and a benign course with headache improvement after several weeks or months.
      There are paediatric patients with atrial septal defect who may dramatically
      develop migraine symptoms with or without aura following percutaneous correction
      of their defect. Large paediatric studies are needed to offer accurate prognoses
      for children and their families. The possibility of using clopidogrel to treat
      this type of headache is subject to debate.

PMID- 17459083
TI  - Burden of cluster headache.
AB  - The aim was to analyse the socioeconomic burden of cluster headache in patients
      from a tertiary headache centre. One hundred consecutive patients from the Danish
      Headache Centre were invited to an interview about the socioeconomic impact of
      cluster headache. Work absence and use of medical services were compared with a
      Danish population-based survey. Eighty-five patients participated; 78% reported
      restrictions in daily living and 13% also outside of cluster periods; 25%
      reported a major decrease in their ability to participate in social activities,
      family life and housework. The disease caused lifestyle changes for 96%, most
      frequently in sleeping habits and avoidance of alcohol. The absence rate among
      patients was 30%, which was significantly higher than 12% among the general
      population (P < 0.001). Use of health services due to headache was also higher
      among the patients (P < 0.001). Cluster headache, although periodic in most
      cases, has considerable impact on social functions, quality of life and use of
      healthcare.

PMID- 17459084
TI  - X-ray tomography of Schizosaccharomyces pombe.
AB  - The genetic tractability of the unicellular yeast Schizosaccharomyces pombe has
      resulted in it becoming an important model organism for the study of many
      eukaryotic cellular processes, in particular cell division. Over the past few
      years much progress has been made toward understanding the mechanisms that
      regulate eukaryotic cell division and the cellular changes that occur-for
      example, the formation of the cytokinetic contractile ring. However, a full
      understanding requires both identification of the proteins involved and
      correlation of this information with images showing the location of molecules in
      context of the cell architecture. Electron microscopic analyses have revealed
      exquisite ultrastructural images of cell structure, but this technique typically
      requires extensive processing-procedures that are labor intensive and time
      consuming. Imaging techniques that can more rapidly obtain better resolution than
      light microscopy are needed to advance the use of this model system for precise
      molecular localization analyses. In this manuscript, we examined S. pombe using
      soft X-ray tomography, an imaging technique that generates three-dimensional (3
      D) images of intact hydrated cells at better than 50 nm isotropic resolution.
      This technique uses X-rays in the "water window," where organic material absorbs
      approximately an order of magnitude more strongly than water, producing high
      contrast images of cellular structures. As cells are examined in the absence of
      any chemical fixatives, stains, or contrast enhancement reagents, the images
      reflect cellular structures in the near-native state. We conducted preliminary
      soft X-ray imaging of S. pombe cells before and during cell division that
      revealed subcellular organelles, the actomyosin ring, and the septum of dividing
      cells. These images reveal tantalizing details of the cytokinesis process and are
      the first steps in our goal of generating a portfolio of tomographic images that
      map the location of labeled molecules into high-resolution 3-D reconstructions of
      the cell.

PMID- 17459085
TI  - Disruption of the dynamic sub-cellular localization of the Xenopus tumorhead
      protein causes embryonic lethality at the early gastrula transition.
AB  - The Xenopus laevis tumorhead (TH) protein, a positive regulator of cell
      proliferation during embryogenesis, shuttles from the cell periphery into the
      nucleus during embryogenesis. In these studies, we performed a detailed analysis
      of TH's subcellular localization pattern to characterize its dynamic behavior. We
      found that TH exhibits distinct patterns of localization in different germ
      layers. At the blastula stage, TH is present in the apical cell periphery of
      prospective mesodermal and ectodermal cells. At the gastrula stage, TH is
      distributed throughout the entire cytoplasm of prospective mesodermal and
      ectodermal cells, whereas it shows nuclear localization in presumptive endodermal
      cells. TH moves into the nucleus of mesodermal and ectodermal cells during the
      neurula and early tailbud stages. To understand if TH is regulated by changes in
      its subcellular localization, we used a TH mutant containing signals for
      farnesylation and palmitoylation to tether the protein to the plasma membrane.
      Ubiquitous overexpression of this mutant causes embryonic lethality at the early
      gastrula transition. Further examination using TUNEL assays indicated that wild
      type TH overexpression induces apoptosis during gastrulation, and that this
      effect is exacerbated by the overexpression of the membrane-bound TH mutant.
      Taken together, our results suggest that changes in the sub-cellular localization
      of the TH protein are important for its function because blocking the nuclear
      translocation of overexpressed TH increases apoptosis and causes embryos to die.
      Our data also suggest that TH plays a role outside the nucleus when it is present
      at the cell periphery.

PMID- 17459086
TI  - Bisphenol A induces permanent squamous change in mouse prostatic epithelium.
AB  - Bisphenol A (BPA) is a monomer of plastic products widely used in daily life, and
      has weak estrogenic activity. In this study, male BALB/c mice were treated with
      BPA and diethylstilbestrol (DES) in adult and fetal periods to investigate
      whether BPA could affect prostatic epithelial differentiation. Eight-to 9-week
      old mice treated for 3 weeks with subcutaneous implants of 0.2-200 mg BPA pellets
      induced the expression of cytokeratin 10 (CK10) in prostatic basal epithelial
      cells in a dose-dependent manner. Utilizing organ culture of adult prostate, 1 nM
      and 1 microM BPA also induced CK10 expression and squamous metaplasia with
      multilayering of basal epithelial cells, respectively. Fetal exposure to low-dose
      BPA (20 microg/kg/day) from gestation day (GD) 13 to GD18 induced permanent CK10
      expression in basal cells of the adult prostate similar to DES (0.2
      microg/kg/day). These results indicate that in mouse, BPA can directly elicit
      CK10 expression in prostatic epithelium, and that this change can be elicited by
      doses as low as 20 microg/kg/day. We speculate that low-dose BPA during fetal
      life may also induce permanent squamous change in human prostate.

PMID- 17459087
TI  - Foxn1 promotes keratinocyte differentiation by regulating the activity of protein
      kinase C.
AB  - The transcription factor Foxn1 (the product of the nude locus) promotes the
      terminal differentiation of epithelial cells in the epidermis and hair follicles.
      Activated early in terminal differentiation, Foxn1 can modulate the timing or
      order of trait acquisition, as it induces early features of epidermal
      differentiation while suppressing late features. Here, we identify protein kinase
      C (PKC) as a key target of Foxn1 in keratinocyte differentiation control. Foxn1
      has broad negative effects on the PKC family, as the loss of Foxn1 function leads
      to higher levels of total, primed, and activated PKC. Phosphorylated PKC
      substrates (the mediators of PKC function) rise when Foxn1 is inactivated and
      fall when Foxn1 is overproduced, suggesting that Foxn1 antagonizes PKC's effects.
      When PKC inhibitors are applied to nude (Foxn1 null) keratinocytes, nude defects
      are normalized or suppressed, as the inhibitors prevent nude cells from
      underproducing early differentiation markers and overproducing late markers.
      Taken together, the results suggest that Foxn1 acts as a restraint or brake on
      PKC signaling and that without this brake PKC disrupts differentiation. The
      results further suggest that Foxn1 modulates stage-specific markers by modulating
      PKC activity, providing control over the timing of steps in the differentiation
      program.

PMID- 17459088
TI  - Tissue-dependent subcellular localization of Drosophila arginine methyl
      transferase 4 (DART4), a coactivator whose overexpression affects neither
      viability nor differentiation.
AB  - Drosophila arginine methyl-transferase 4 (DART4) belongs to the type I class of
      arginine methyltransferases. It catalyzes the methylation of arginine residues to
      monomethylarginines and asymmetrical dimethylarginines. The DART4 sequence is
      highly similar to mammalian PRMT4/CARM1, and DART4 substrate specificity has been
      conserved, too. Recently it was suggested that DART4/Carmer functions in ecdysone
      receptor mediated apoptosis of the polytene larval salivary glands and an
      apparent up-regulation of DART4/Carmer mRNA levels before tissue histolysis was
      reported. Here we show that in Drosophila larvae, DART4 is mainly expressed in
      the imaginal disks and in larval brains, and to a much lesser degree in the
      polytene larval tissue such as salivary glands. In glands, DART4 protein is
      present in the cytoplasm and the nucleus. The nuclear signal emanates from the
      extrachromosomal domain and gets progressively restricted to the region of the
      nuclear lamina upon pupariation. Surprisingly, DART4 levels do not increase in
      salivary glands during pupariation, and overexpression of DART4 does not cause
      precautious cell death in the glands. Furthermore, over- and misexpression of
      DART4 under the control of the alpha tubulin promoter do not lead to any major
      problem in the life of a fly. This suggests that DART4 activity is regulated at
      the posttranslational level and/or that it acts as a true cofactor in vivo. We
      present evidence that nuclear localization of DART4 may contribute to its
      function because DART4 accumulation changes from a distribution with a strong
      cytoplasmic component during the transcriptional quiescence of the young embryo
      to a predominantly nuclear one at the onset of zygotic transcription.

PMID- 17459089
TI  - Fetal bovine serum enables cardiac differentiation of human embryonic stem cells.
AB  - During development, cardiac commitment within the mesoderm requires endoderm
      secreted factors. Differentiation of embryonic stem cells into the three germ
      layers in vitro recapitulates developmental processes and can be influenced by
      supplements added to culture medium. Hence, we investigated the effect of fetal
      bovine serum (FBS) and KnockOut serum replacement (SR) on germ layers
      specification and cardiac differentiation of H1 human embryonic stem cells (hESC)
      within embryoid bodies (EB). At the time of EB formation, FBS triggered an
      increased apoptosis. As assessed by quantitative PCR on 4-, 10-, and 20-day-old
      EB, FBS promoted a faster down-regulation of pluripotency marker Oct4 and an
      increased expression of endodermal (Sox17, alpha-fetoprotein, AFP) and mesodermal
      genes (Brachyury, CSX). While neuronal and hematopoietic differentiation occurred
      in both supplements, spontaneously beating cardiomyocytes were only observed in
      FBS. Action potential (AP) morphology of hESC-derived cardiomyocytes indicated
      that ventricular cells were present only after 2 months of culture. However,
      quantification of myosin light chain 2 ventricular (mlc2v)-positive areas
      revealed that mlc2v-expressing cardiomyocytes could be detected already after 2
      weeks of differentiation, but not in all beating clusters. In conclusion, FBS
      enabled cardiac differentiation of hESC, likely in an endodermal-dependent
      pathway. Among cardiac cells, ventricular cardiomyocytes differentiated over
      time, but not as the predominant cardiac cell subtype.

PMID- 17459090
TI  - Lens fiber cell elongation and differentiation is associated with a robust
      increase in myosin light chain phosphorylation in the developing mouse.
AB  - Myosin II, a molecular motor, plays a critical role in cell migration, cell shape
      changes, cell adhesion, and cytokinesis. To understand the role of myosin II in
      lens fiber cell elongation and differentiation, we determined the distribution
      pattern of nonmuscle myosin IIA, IIB, and phosphorylated regulatory myosin light
      chain-2 (phospho-MLC) in frozen sections of the developing mouse lens by
      immunofluorescence analysis. While myosin IIA was distributed uniformly
      throughout the differentiating lens, including the epithelium and fibers, myosin
      IIB was localized predominantly to the epithelium and the posterior tips of the
      lens fibers. In contrast, immunostaining with a di-phospho-MLC antibody localized
      intensely and precisely to the elongating and differentiating primary and
      secondary lens fibers, co-localizing with actin filaments. An in situ analysis of
      Rho GTPase activation revealed that Rho-GTP was distributed uniformly throughout
      the embryonic lens, including epithelium and fibers. Inhibition of myosin light
      chain kinase (MLCK) activity by ML-7 in organ cultured mouse lenses led to
      development of nuclear lens opacity in association with abnormal fiber cell
      organization. Taken together, these data reveal a distinct spatial distribution
      pattern of myosin II isoforms in the developing lens and a robust activation of
      MLC phosphorylation in the differentiating lens fibers. Moreover, the regulation
      of MLC phosphorylation by MLCK appears to be critical for crystallin organization
      and for maintenance of lens transparency and lens membrane function.

PMID- 17459091
TI  - Comparative analysis of Xenopus VegT, the meso-endodermal determinant, identifies
      an unusual conserved sequence.
AB  - The transcription factor, VegT, is the meso-endodermal determinant in Xenopus
      laevis. We examined VegT orthologs from several anuran amphibians and the urodele
      amphibian, the Mexican axolotl. In addition to the conserved T-box, the DNA
      binding domain, the orthologs share a conserved 57 amino acid domain at the C
      terminal. Most striking is a 17-nucleotide (nt) sequence near the 3' end of the
      open reading frame. The 17 nts are absolutely conserved among the anurans, whose
      last common ancestor lived 200 million years ago. As an initial test of the
      function of the 17 nts, 27 or 49 amino acids, which include the six amino acids
      coded by the 17 (+1) nts, were deleted from the C-terminal of VegT. These
      truncated VegT's retained some transcriptional activity, indicating that the 17
      nts are not absolutely required for this function. The function of the highly
      conserved 17 nts is unknown. Two possibilities are that the conserved 17 nts
      interact with the cytoskeleton or that they are a target for regulation by a
      microRNA.

PMID- 17459092
TI  - Association of erythrocyte indices with glycated haemoglobin in pre-menopausal
      women.
AB  - AIMS: Although HbA(1c) is known to be affected by the lifespan of erythrocytes,
      any association of erythrocyte indices with HbA(1c) in subjects without anaemia
      is poorly understood. Pre-menopausal women may be relatively iron deficient
      because of menstruation. In this study, we examined the relationship between
      HbA(1c) and erythrocyte indices in pre- and post-menopausal women. METHODS: We
      determined HbA(1c), red blood cell (RBC) count, haematocrit, haemoglobin, mean
      corpuscular volume (MCV) and mean corpuscular haemoglobin (MCH) in 423 women with
      normal glucose tolerance who had undergone health checks. In addition, age at
      menopause was recorded in post-menopausal subjects. RESULTS: RBC counts of the
      180 pre-menopausal women were positively associated with HbA(1c), whereas
      haemoglobin, MCV and MCH showed a negative association. In contrast, no
      significant association of any indices with HbA(1c) was detected in the 243 post
      menopausal women. Stepwise multivariate regression analysis in the pre-menopausal
      women identified fasting plasma glucose and age as positively associated and MCH
      as negatively associated with HbA(1c), regardless of whether or not these pre
      menopausal women were anaemic. CONCLUSIONS: Erythrocyte indices are associated
      with HbA(1c), independently of plasma glucose levels, in pre-menopausal women
      even when they are not anaemic. This should be appreciated when interpreting
      HbA(1c) in pre-menopausal patients with diabetes.

PMID- 17459093
TI  - The influence of health threat communication and personality traits on personal
      models of diabetes in newly diagnosed diabetic patients.
AB  - BACKGROUND: Personal models of diabetes, i.e. patients' beliefs about symptoms,
      treatment effectiveness, consequences (impact on life, seriousness) and emotional
      response to possible short- and long-term complications, have been associated
      with diabetes self-care behaviours. Little work has examined potential
      determinants of personal models. AIMS: To examine the influence of health threat
      communication and personality traits on personal models in newly diagnosed
      patients. METHODS: Newly diagnosed patients (n = 158; 32 Type 1 and 126 Type 2)
      completed the Big Five Personality Inventory, Diabetes Health Threat
      Communication Questionnaire (DHTCQ), Personal Models of Diabetes Interview
      Adapted (PMDI) and Illness Perception Questionnaire-Revised (IPQ-R). RESULTS:
      Emotional responses to diabetes (PMDI) were associated with perceptions of a more
      threatening health message (22% explained variance), less emotional stability
      (5%) and the presence of dependent children (3%). Emotional representations (IPQ
      R) were associated with a threatening health message (6%) and less emotional
      stability (15%). An adverse view of consequences (PMDI) was predicted by a more
      threatening/less reassuring health message (15%), less emotional stability (6%)
      and Type 1 diabetes (4%). Consequences (IPQ-R) were predicted by perceptions of a
      more threatening health message (20%), being less agreeable/cooperative (7%) and
      having dependent children (4%). Treatment effectiveness beliefs (PMDI) were
      associated with perceptions of a more reassuring health message (31%), younger
      age (3%) and more openness/intellect (2%). CONCLUSIONS: Personal models of
      diabetes are influenced by health threat communication, demographic and
      personality factors. These findings support the concept of tailoring health
      messages to the needs of individual patients and provide information on factors
      to be taken into account in the education process.

PMID- 17459094
TI  - A method for assessing quality of control from glucose profiles.
AB  - AIM: As the practice of multiple assessments of glucose concentration throughout
      the day increases for people with diabetes, there is a need for an assessment of
      glycaemic control weighted for the clinical risks of both hypoglycaemia and
      hyperglycaemia. METHODS: We have developed a methodology to report the degree of
      risk which a glycaemic profile represents. Fifty diabetes professionals assigned
      risk values to a range of 40 blood glucose concentrations. Their responses were
      summarised and a generic function of glycaemic risk was derived. This function
      was applied to patient glucose profiles to generate an integrated risk score
      termed the Glycaemic Risk Assessment Diabetes Equation (GRADE). The GRADE score
      was then reported by use of the mean value and the relative percent contribution
      to the weighted risk score from the hypoglycaemic, euglycaemic, hyperglycaemic
      range, respectively, e.g. GRADE (hypoglycaemia%, euglycaemia%, hyperglycaemia%).
      RESULTS: The GRADE scores of indicative glucose profiles were as follows:
      continuous glucose monitoring profile non-diabetic subjects GRADE = 1.1, Type 1
      diabetes continuous glucose monitoring GRADE = 8.09 (20%, 8%, 72%), Type 2
      diabetes home blood glucose monitoring GRADE = 9.97 (2%, 7%, 91%). CONCLUSIONS:
      The GRADE score of a glucose profile summarises the degree of risk associated
      with a glucose profile. Values < 5 correspond to euglycaemia. The GRADE score is
      simple to generate from any blood glucose profile and can be used as an adjunct
      to HbA1c to report the degree of risk associated with glycaemic variability.

PMID- 17459095
TI  - A -243A-->G polymorphism upstream of the gene encoding GAD65 associates with
      lower levels of body mass index and glycaemia in a population-based sample of
      5857 middle-aged White subjects.
AB  - AIMS: The glutamate decarboxylase gene (GAD2) encodes GAD65, an enzyme catalysing
      the production of the gamma-aminobutyric acid (GABA) which interacts with
      neuropeptide Y to stimulate food intake. It has been suggested that in pancreatic
      islets, GABA serves as a functional regulator of pancreatic hormone release.
      Conflicting results have been reported concerning the potential impact of GAD2
      variation on estimates of energy metabolism. The aim of this study was to
      elucidate potential associations between the GAD2-243A-->G polymorphism and
      levels of body mass index (BMI) and estimates of glycaemia. METHODS: Using high
      throughput chip-based matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry, the GAD2-243A-->G (rs2236418) polymorphism was genotyped in a
      population-based sample (Inter99) of 5857 middle-aged, unrelated Danish White
      subjects. RESULTS: The G-allele was associated with modestly lower BMI (P =
      0.01). In a case-control study of obesity, the G-allele frequency in 2582
      participants with BMI < 25 kg/m2 was 19.5% (18.4-20.6) compared with 17.1% (15.5
      18.8) in 968 participants having BMI > or = 30 kg/m2 (P = 0.03), odds ratio 0.9
      (0.7-1.0). Of the 5857 subjects, GG carriers had lower fasting plasma glucose
      levels (mmol/l) [AA (n = 3859) 5.6 +/- 0.8; AG (n = 1792) 5.5 +/- 0.8; GG (n =
      206) 5.5 +/- 0.8, P = 0.008] and lower 30-min oral glucose tolerance test (OGTT)
      related plasma glucose levels (AA 8.7 +/- 1.9; AG 8.6 +/- 1.9; GG 8.6 +/- 2.0, P
      = 0.04), adjusted for sex, age and BMI. Analysing subjects who were both
      normoglycaemic and glucose tolerant (n = 4431) GG carriers still had lower
      fasting plasma glucose concentrations: AA (n = 2895) 5.3 +/- 0.4; AG (n = 1383)
      5.3 +/- 0.4; GG (n = 153) 5.2 +/- 0.4 (P = 9.10(-5)). CONCLUSION: The present
      study suggests that the GAD2-243A-->G polymorphism in a population of middle-aged
      White people associates with a modest reduction in BMI and fasting and OGTT
      related plasma glucose levels.

PMID- 17459096
TI  - The effects of orlistat and fenofibrate, alone or in combination, on high-density
      lipoprotein subfractions and pre-beta1-HDL levels in obese patients with
      metabolic syndrome.
AB  - OBJECTIVE: We assessed the effect of orlistat and fenofibrate, alone or in
      combination, on plasma high-density lipoprotein (HDL) subfractions and plasma pre
      beta1-HDL levels in overweight and obese subjects with metabolic syndrome (MetS).
      METHODS: Patients (n = 89) were prescribed a low-fat low-calorie diet and were
      randomly allocated to receive orlistat 120 mg three times daily (O group),
      micronized fenofibrate 200 mg/day (F group) or both (OF group) for 6 months. HDL
      subfractions were determined using a polyacrylamide gel tube electrophoresis
      method and pre-beta1-HDL levels using enzyme-linked immunoabsorbent assay.
      RESULTS: We observed a significant change of high-density lipoprotein cholesterol
      (HDL-C) levels only in the F group (+3%, p < 0.05). Large HDL-C levels were
      significantly increased and small HDL-C levels were significantly reduced with O
      administration. In F group we observed a significant increase of small HDL-C
      levels. No significant change of large or small HDL-C levels was observed with
      combination treatment. We observed a significant increase of pre-beta1-HDL levels
      in all groups, which was significantly greater in OF group compared with O or F
      monotherapy. CONCLUSION: OF combination increased the antiatherogenic pre-beta1
      HDL levels in overweight and obese patients with MetS. Furthermore, OF
      combination counterbalanced the reduction of small HDL-C levels observed with
      orlistat monotherapy.

PMID- 17459097
TI  - Subunit S5a of the 26S proteasome is regulated by antiapoptotic signals.
AB  - We performed a functional genetic screen to find novel antiapoptotic genes that
      are under the regulation of the oncoprotein c-Src. Several clones were
      identified, including subunit S5a of the 26S proteasome. We found that S5a
      rescued Saos-2 cells from apoptosis induced by Src inhibitor 4-amino-5-(4
      methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1). S5a mRNA and protein
      levels were downregulated as a result of Src inhibition, either by siRNA or PP1.
      In cell lines that possess high activity of Src S5a levels were elevated. Cloning
      of the S5a promoter region showed that S5a transcription responds to several
      stimuli. Analysis of the promoter sequence revealed a binding site for Tcf/Lef-1
      transcription factor. Indeed, beta-catenin significantly induced transcription
      from the S5a promoter, whereas EMSA studies showed that Lef-1 binds the S5a
      promoter-binding site. Furthermore, we also found that PP1 and LY294002, but not
      PD98059 inhibit the S5a promoter activity. These results suggest that S5a is
      regulated during apoptosis at the transcriptional level and that S5a upregulation
      by antiapoptotic signals can contribute to cell survival.

PMID- 17459098
TI  - The intrinsic structure of glucose transporter isoforms Glut1 and Glut3 regulates
      their differential distribution to detergent-resistant membrane domains in
      nonpolarized mammalian cells.
AB  - The hexose transporter family, which mediates facilitated uptake in mammalian
      cells, consists of more than 10 members containing 12 membrane-spanning segments
      with a single N-glycosylation site. We previously demonstrated that glucose
      transporter 1 is organized into a raft-like detergent-resistant membrane domain
      but that glucose transporter 3 distributes to fluid membrane domains in
      nonpolarized mammalian cells. In this study, we further examined the structural
      basis responsible for the distribution by using a series of chimeric constructs.
      Glucose transporter 1 and glucose transporter 3 with a FLAG-tagged N-terminus
      were expressed in detergent-resistant membranes and non-detergent-resistant
      membranes of CHO-K1 cells, respectively. Replacement of either the C-terminal or
      N-terminal cytosolic portion of FLAG-tagged glucose transporter 1 and glucose
      transporter 3 did not affect the membrane distribution. However, a critical
      sorting signal may exist within the N-terminal half of the isoforms without
      affecting transport activity and its inhibition by cytochalasin B. Further
      shortening of these regions altered the critical distribution, suggesting that a
      large proportion or several parts of the intrinsic structure, including the N
      terminus of each isoform, are involved in the regulation.

PMID- 17459099
TI  - Site-directed mutagenesis of the active site loop of the rhodanese-like domain of
      the human molybdopterin synthase sulfurase MOCS3. Major differences in substrate
      specificity between eukaryotic and bacterial homologs.
AB  - Sequence alignments of human molybdopterin synthase sulfurase, MOCS3, showed that
      the N-terminal domain is homologous to Escherichia coli MoeB, whereas the C
      terminal domain is homologous to rhodanese-like proteins. Previous studies showed
      that the activity of the separately purified rhodanese-like domain of MOCS3
      displayed 1000-fold lower activity in comparison to bovine rhodanese with
      thiosulfate as sulfur source. When the six amino acid active site loop of MOCS3
      rhodanese-like domain was exchanged with the loop found in bovine rhodanese,
      thiosulfate:cyanide sulfurtransferase activity was increased 165-fold. Site
      directed mutagenesis of each individual residue of the active site loop of the
      MOCS3 rhodanese-like domain showed that the charge of the last amino acid
      determines thiosulfate sulfurtransferase activity. Replacing Asp417 by threonine
      resulted in 90-fold increased activity, whereas replacing it by arginine
      increased the activity 470-fold. Using a fully defined in vitro system containing
      precursor Z, MOCS2A, E. coli MoaE, E. coli MoeB, Mg-ATP, MOCS3 rhodanese-like
      domain, and thiosulfate, it was shown that sulfur transfer to MOCS2A was also
      affected by the alterations, but not as drastically. Our studies revealed that in
      humans and most eukaryotes thiosulfate is not the physiologic sulfur donor for
      MOCS3, whereas in bacterial homologs, which have an arginine at the last position
      of the active site loop, thiosulfate can be used as a sulfur source for
      molybdenum cofactor biosynthesis. The phylogenetic analysis of MoeB homologs
      showed that eukaryotic homologs are of bacterial origin. Furthermore, it could be
      shown that an MoeB homolog named MoeZ, where the dual CXXC zinc-binding motif of
      the MoeB domain is not present, arose independently several times during
      evolution.

PMID- 17459100
TI  - Identification of substrates for transglutaminase in Physarum polycephalum, an
      acellular slime mold, upon cellular mechanical damage.
AB  - Transglutaminases are Ca(2+)-dependent enzymes that post-translationally modify
      proteins by crosslinking or polyamination at specific polypeptide-bound glutamine
      residues. Physarum polycephalum, an acellular slime mold, is the evolutionarily
      lowest organism expressing a transglutimase whose primary structure is similar to
      that of mammalian transglutimases. We observed transglutimase reaction products
      at injured sites in Physarum macroplasmodia upon mechanical damage. With use of a
      biotin-labeled primary amine, three major proteins constituting possible
      transglutimase substrates were affinity-purified from the damaged slime mold. The
      purified proteins were Physarum actin, a 40 kDa Ca(2+)-binding protein with four
      EF-hand motifs (CBP40), and a novel 33 kDa protein highly homologous to the
      eukaryotic adenine nucleotide translocator, which is expressed in mitochondria.
      Immunochemical analysis of extracts from the damaged macroplasmodia indicated
      that CBP40 is partly dimerized, whereas the other proteins migrated as monomers
      on SDS/PAGE. Of the three proteins, CBP40 accumulated most significantly around
      injured areas, as observed by immunofluoresence. These results suggested that
      transglutimase reactions function in the response to mechanical injury.

PMID- 17459101
TI  - Enzymatic properties of the lactate dehydrogenase enzyme from Plasmodium
      falciparum.
AB  - The lactate dehydrogenase enzyme from Plasmodium falciparum (PfLDH) is a target
      for antimalarial compounds owing to structural and functional differences from
      the human isozymes. The plasmodial enzyme possesses a five-residue insertion in
      the substrate-specificity loop and exhibits less marked substrate inhibition than
      its mammalian counterparts. Here we provide a comprehensive kinetic analysis of
      the enzyme by steady-state and transient kinetic methods. The mechanism deduced
      by product inhibition studies proves that PfLDH shares a common mechanism with
      the human LDHs, that of an ordered sequential bireactant system with coenzyme
      binding first. Transient kinetic analysis reveals that the major rate-limiting
      step is the closure of the substrate-specificity loop prior to hydride transfer,
      in line with other LDHs. The five-residue insertion in this loop markedly
      increases substrate specificity compared with the human muscle and heart
      isoforms.

PMID- 17459102
TI  - Sensor of phospholipids in Streptomyces phospholipase D.
AB  - Recently, we identified Ala426 and Lys438 of phospholipase D from Streptomyces
      septatus TH-2 (TH-2PLD) as important residues for activity, stability and
      selectivity in transphosphatidylation. These residues are located in a C-terminal
      flexible loop separate from two catalytic HxKxxxxD motifs. To study the role of
      these residues in substrate recognition, we evaluated the affinities of inactive
      mutants, in which these residues were substituted with Phe and His, toward
      several phospholipids by SPR analysis. By substituting Ala426 and Lys438 with Phe
      and His, respectively, the inactive mutant showed a much stronger interaction
      with phosphatidylcholine and a weaker interaction with phosphatidylglycerol than
      the inactive TH-2PLD mutant. We demonstrated that Ala426 and Lys438 of TH-2PLD
      play a role in sensing the head group of phospholipids.

PMID- 17459103
TI  - Seven-up facilitates insect counter-defense by suppressing cathepsin B
      expression.
AB  - When challenged by the dietary soybean cysteine protease inhibitor scN, the
      cowpea bruchid (Callosobruchus maculatus) adapts to the inhibitory effects by
      readjusting the transcriptome of its digestive system, including the specific
      activation of a cathepsin B-like cysteine protease CmCatB. To understand the
      transcriptional regulation of CmCatB, we cloned a portion of its promoter and
      demonstrated its activity in Drosophila cells using a chloramphenicol
      acetyltransferase reporter system. EMSAs detected differential DNA-binding
      activity between nuclear extracts of scN-adapted and -unadapted midguts. Two
      tandem chicken ovalbumin upstream promoter (COUP) elements were identified in the
      CmCatB promoter that specifically interacted with a protein factor unique to
      nuclear extracts of unadapted insect guts, where CmCatB expression was repressed.
      Seven-up (Svp) is a COUP-TF-related transcription factor that interacted with the
      COUP responsive element. Polyclonal anti-(mosquito Svp) serum abolished the
      specific DNA-binding activity in cowpea bruchid midgut extracts, suggesting that
      the protein factor is an Svp homolog. Subsequent cloning of a cowpea bruchid Svp
      (CmSvp) indicated that it shares a high degree of amino acid sequence similarity
      with COUP-TF/Svp orphan nuclear receptor family members from varied species. The
      protein was more abundant in scN-unadapted insect guts than scN-adapted guts,
      consistent with the observed DNA-binding activity. Furthermore, CmCatB expression
      was repressed when CmSvp was transiently expressed in Drosophila cells, most
      likely through COUP binding. These findings indicate that CmSvp may contribute to
      insect counter-defense, in part by inhibiting CmCatB expression under normal
      growth conditions, but releasing the inhibition when insects are challenged by
      dietary protease inhibitors.

PMID- 17459104
TI  - Distinct types of ionic modulation of GABA actions in pyramidal cells and
      interneurons during electrical induction of hippocampal seizure-like network
      activity.
AB  - It has recently been shown that electrical stimulation in normal extracellular
      fluid induces seizure-like afterdischarge activity that is always preceded by
      GABA-dependent slow depolarization. These afterdischarge responses are
      synchronous among mature hippocampal neurons and driven by excitatory GABAergic
      input. However, the differences in the mechanisms whereby the GABAergic signals
      in pyramidal cells and interneurons are transiently converted from
      hyperpolarizing to depolarizing (and even excitatory) have remained unclear. To
      clarify the network mechanisms underlying this rapid GABA conversion that induces
      afterdischarges, we examined the temporal changes in GABAergic responses in
      pyramidal cells and/or interneurons of the rat hippocampal CA1 area in vitro. The
      extents of slow depolarization and GABA conversion were much larger in the
      pyramidal cell group than in any group of interneurons. Besides GABA(A) receptor
      activation, neuronal excitation by ionotropic glutamate receptors enhanced GABA
      conversion in the pyramidal cells and consequent induction of afterdischarge. The
      slow depolarization was confirmed to consist of two distinct phases; an early
      phase that depended primarily on GABA(A)-mediated postsynaptic Cl- accumulation,
      and a late phase that depended on extracellular K+ accumulation, both of which
      were enhanced by glutamatergic neuron excitation. Moreover, extracellular K+
      accumulation augmented each oscillatory response of the afterdischarge, probably
      by further Cl- accumulation through K+-coupled Cl- transporters. Our findings
      suggest that the GABA reversal potential may be elevated above their spike
      threshold predominantly in the pyramidal cells by biphasic Cl- intrusion during
      the slow depolarization in GABA- and glutamate-dependent fashion, leading to the
      initiation of seizure-like epileptiform activity.

PMID- 17459105
TI  - Kynurenic acid blocks nicotinic synaptic transmission to hippocampal interneurons
      in young rats.
AB  - The tryptophan metabolite kynurenic acid can block glutamate at ionotropic
      receptors, but recent evidence suggests a more potent antagonistic action at
      alpha7 nicotinic receptors for acetylcholine on cultured neurons. The present
      study examines activity of kynurenic acid at those nicotinic receptors, which
      mediate cholinergic neurotransmission onto interneurons in the rat hippocampus.
      Intracellular recordings were made from pyramidal cells and interneurons in the
      presence of atropine, bicuculline methobromide, (3-aminopropyl)(diethoxymethyl)
      phosphinic acid [CGP35348, to block gamma-aminobutyric acid (GABA)(B) receptors]
      and 3-tropanyl-3,5-dichlorobenzoate (MDL 72222, to block 5-HT3 receptors). In the
      added presence of glutamate antagonists 2-amino-5-phosphono-pentanoic acid and 6
      cyano-7-nitroquinoxaline-2,3-dione, interneurons exhibited a residual excitatory
      postsynaptic potential (EPSP) that could be blocked by the nicotinic alpha7
      receptor blocker methyl-lycaconitine, but not by dihydro-beta-erythroidine which
      blocks alpha4beta2 receptors. Kynurenic acid reduced the amplitude of these EPSPs
      with an EC50 of 136 microM. The amplitudes of nicotinic spontaneous miniature
      EPSPs were also reduced by methyl-lycaconitine and kynurenic acid. The results
      show that kynurenic acid is more potent in blocking nicotinic EPSPs compared with
      the full, glutamate-mediated EPSPs, but it was substantially less potent than has
      been reported in cultures, possibly because of differences in the accessibility
      of synaptic and extrasynaptic receptors. It is suggested that blockade of
      nicotinic synaptic transmission may be relevant to the actions of kynurenic acid
      in the hippocampus, but that in the intact brain this activity is likely to be
      comparable in importance to the blockade of glutamate-mediated transmission.

PMID- 17459106
TI  - Acute retinal ganglion cell injury caused by intraocular pressure spikes is
      mediated by endogenous extracellular ATP.
AB  - Elevated intraocular pressure may lead to retinal ganglion cell injury and
      consequent visual deficits. Chronic intraocular pressure increase is a major risk
      factor for glaucoma, a leading blinding disease, and permanent visual deficits
      can also occur following acute pressure increments due to trauma, acute glaucoma
      or refractive surgery. How pressure affects retinal neurons is not firmly
      established. Mechanical damage at the optic nerve head, reduced blood supply,
      inflammation and cytotoxic factors have all been called into play. Reasoning that
      the analysis of retinal neurons soon after pressure elevation would provide
      useful cues, we imaged individual ganglion cells in isolated rat retinas before
      and after short hydrostatic pressure increments. We found that slowly rising
      pressure to peaks observed in trauma, acute glaucoma or refractive surgery (50-90
      mmHg) did not damage ganglion cells, whereas a rapid 1 min pulse to 50 mmHg
      injured 30% of these cells within 1 h. The severity of damage and the number of
      affected cells increased with stronger or repeated insults. Degrading
      extracellular ATP or blocking the P2X receptors for ATP prevented acute pressure
      induced damage in ganglion cells. Similar effects were observed in vivo. A short
      intraocular pressure transient increased extracellular ATP levels in the eye
      fluids and damaged ganglion cells within 1 h. Reducing extracellular ATP in the
      eye prevented damage to ganglion cells and accelerated recovery of their response
      to light. These data show that rapid pressure transients induce acute ganglion
      cell injury and unveil the causal role of extracellular ATP elevation in such
      injury.

PMID- 17459107
TI  - Order-specific quantitative patterns of cortical gyrification.
AB  - Why the extent of cortical gyrification varies across mammals of different brain
      sizes is a problem that is not clearly understood. The aim of the present study
      was to test a hypothesis indicating that the order is a significant phylogenetic
      grouping in terms of quantifiable gyrification indices (GIs) and thus variation
      between mammals. The GI was determined from serial sections of the brain of 25
      different mammalian species, representing four different orders: primates,
      carnivores, ungulates and rodents. Image J analysis was used to measure the
      contours of the cerebral cortex, and the GI was calculated using three different
      methods of analysis: complete vs outer; gyral vs sulcal; and outer vs inner
      surface contours. The measurements were then computed against the brain weights
      of each species within the order. An increasing GI correlates with an increasing
      brain weight in all the mammalian orders. Each order has its own specific
      allometric pattern that is significantly different from the other orders. The
      ungulates were the mammals with the most gyrencephalic brains, these species
      being significantly more gyrencephalic than all other mammals when species of
      similar brain weights are compared. The North American beaver has an atypically
      lissencephalic brain for its size, differing from the trend for increased
      gyrencephaly found in the other rodent species examined. Our results show
      definite trends and patterns specific to each order; thus, it would seem that the
      order is a significant phylogenetic grouping in terms of this neural parameter,
      from which we can predict with a reasonable degree of certainty the GI of any
      species of a particular order given the brain weight.

PMID- 17459108
TI  - Arvanil, anandamide and N-arachidonoyl-dopamine (NADA) inhibit emesis through
      cannabinoid CB1 and vanilloid TRPV1 receptors in the ferret.
AB  - Cannabinoid (CB) agonists suppress nausea and vomiting (emesis). Similarly,
      transient receptor potential vanilloid-1 (TRPV1) receptor agonists are anti
      emetic. Arvanil, N-(3-methoxy-4-hydroxy-benzyl)-arachidonamide, is a synthetic
      'hybrid' agonist of CB1 and TRPV1 receptors. Anandamide and N-arachidonoyl
      dopamine (NADA) are endogenous agonists at both these receptors. We investigated
      if arvanil, NADA and anandamide were anti-emetic in the ferret and their
      mechanism of action. All compounds reduced the episodes of emesis in response to
      morphine 6 glucuronide. These effects were attenuated by AM251, a CB1 antagonist
      that was pro-emetic per se, and TRPV1 antagonists iodoresiniferatoxin and AMG
      9810, which were without pro-emetic effects. Similar sensitivity to arvanil and
      NADA was found for prodromal signs of emesis. We analysed the distribution of
      TRPV1 receptors in the ferret brainstem and, for comparison, the co-localization
      of CB1 and TRPV1 receptors in the mouse brainstem. TRPV1 immunoreactivity was
      largely restricted to the nucleus of the solitary tract of the ferret, with faint
      labeling in the dorsal motor nucleus of the vagus and sparse distribution in the
      area postrema. A similar distribution of TRPV1, and its extensive co-localization
      with CB1, was observed in the mouse. Our findings suggest that CB1 and TRPV1
      receptors in the brainstem play a major role in the control of emesis by agonists
      of these two receptors. While there appears to be an endogenous 'tone' of CB1
      receptors inhibiting emesis, this does not seem to be the case for TRPV1
      receptors, indicating that endogenously released endocannabinoids/endovanilloids
      inhibit emesis preferentially via CB1 receptors.

PMID- 17459109
TI  - Comparison of differential neuronal responsiveness for different regions of the
      prefrontal cortex in a conditional visual discrimination task.
AB  - To investigate neuronal processing during monkeys' performance of a visual
      conditional discrimination task, recordings were made from four areas of
      prefrontal cortex (ventromedial, orbitofrontal, dorsolateral and anterior
      cingulate) where lesions have been shown to produce impairment of such tasks. Of
      1911 recorded neurons, 573 (31%) responded to elements of the task. This
      proportion was less than the 50% previously reported as responsive in temporal
      cortex under the same conditions, suggesting sparser encoding in prefrontal than
      temporal cortex. Of the responsive prefrontal neurons, 165 (29%) responded
      differently on the different types of trial, so signalling various types of
      information relevant to task performance and cognition. In line with recent
      lesion findings, in the dorsolateral region the incidence of such differentially
      responsive neurons was only an eighth that in the other regions. The relatively
      high incidence of neuronal responses that encoded a potential instruction cue
      rather than specific individual stimulus arrangements was consistent with the
      animals solving the task by using such information, though other neuronal
      responses could have enabled the task to have been solved by rote learning.
      Compared to temporal neurons, prefrontal responses more frequently coded
      information relating to the planned behavioural response rather than perceptual
      aspects of the task. Population differential response latencies were long (>
      approximately 225 ms) in prefrontal cortex. A comparison of such differential
      latencies between temporal and prefrontal cortex indicated that potential
      information flow was likely to be primarily from temporal to prefrontal cortex
      rather than vice versa.

PMID- 17459110
TI  - Efferent connections of the ventral auditory area in the rat cortex: implications
      for auditory processing related to emotion.
AB  - In the rat auditory cortex, ventral (VA) and posterodorsal (PD) areas are the two
      major auditory fields that receive thalamic afferents from the dorsal division of
      the medial geniculate body (MGD). VA and PD are presumed to serve distinct
      functions in tandem as the pair of major cortical recipients of extralemniscal
      thalamic inputs. To deduce the functional significance of VA, efferent
      connections of VA were examined with the anterograde tracer biocytin. VA lies
      primarily in the ventral margin of area Te1 and represents frequencies primarily
      < 15 kHz [Donishi, T., Kimura, A., Okamoto, K. & Tamai, Y. (2006) Neuroscience,
      141, 1553-1567.] Biocytin was iontophoretically injected into cortical regions
      which were defined as VA based on histological location, auditory response and
      thalamocortical connectivity. Anterograde labelling revealed two important
      aspects of cortical projections. First, VA sent a projection to a well-confined
      region in the caudal end of the insular cortex (Ins) pivotal for fear memory
      formation during aversive conditioning. Second, VA sent parallel projections to
      cortical regions that probably comprise the other nonprimary auditory fields,
      including PD. The results suggest that VA relays auditory input from the MGD to
      the Ins for affective memory formation and at the same time dispatches the
      auditory signal, which may represent emotional content, to the remaining
      nonprimary auditory fields. PD is assumed to play a pivotal role in auditory
      spatial processing for directed attention (Kimura et al., 2004). As the
      counterpart of PD, VA is assumed to give rise to another major stream of cortical
      information processing, most probably related to emotion.

PMID- 17459111
TI  - Phasic and tonic firing properties in rat oculomotor nucleus motoneurons, studied
      in vitro.
AB  - Alert-chronic studies show that ocular motoneurons (Mns) exhibit a phasic and
      tonic firing correlated with eye saccade-velocity and position (fixation),
      respectively. Differences in the phasic and tonic firing among Mns depend on
      synaptic inputs and/or the intrinsic membrane properties. We have used in vitro
      slice preparation to investigate the contribution of membrane properties to
      firing properties of Wistar rat oculomotor nucleus Mns. We recorded different
      discharge patterns and focused on Mns with sustained discharge (type I) because
      they were the most abundant, and their firing pattern resembles that reported in
      alert preparations. Various differences divided these Mns into types I(A) and
      I(B); the afterhyperpolarization (AHP) phase of the spike was monophasic in I(A)
      and biphasic in I(B); I(A) Mns showed tonic or phasic-tonic firing depending on
      the current intensity, while I(B) Mns showed phasic-tonic discharge; the phasic
      firing was higher in I(B) than in I(A) Mns; I(A) Mns fired in a narrower range
      than did I(B) Mns; and I(A) Mns showed lower maximum frequency than did I(B) Mns.
      In conclusion, I(A) and I(B) Mns show different phasic firing properties and
      dynamic range, supported by intrinsic membrane properties. We suggest that I(A)
      and I(B) Mns innervate fast-twitch muscle fibres with different contraction
      speeds, and could contribute to generating a fine phasic signal for a graded
      muscle contraction. Finally, we have demonstrated an inverse relationship between
      Mn thresholds and tonic firing gain, concluding that intrinsic membrane
      properties could not support the covariation between tonic firing gain and
      recruitment thresholds reported in alert studies.

PMID- 17459112
TI  - Porphyromonas gingivalis infection and cell death in human aortic endothelial
      cells.
AB  - Porphyromonas gingivalis is a periodontal pathogen that promotes a proatherogenic
      response in endothelial cells. Cell death responses of human aortic endothelial
      cells to P. gingivalis at various multiplicities of infection (MOI) were
      investigated by assessment of cell detachment, histone-associated DNA
      fragmentation, lactate dehydrogenase release and ADP:ATP ratio. Porphyromonas
      gingivalis at MOI 1:10-1:100 did not have a cytotoxic effect, but induced
      apoptotic cell death at MOI 1:500 and 1:1000. Monocyte chemoattractant protein-1
      production was significantly enhanced by P. gingivalis at MOI 1:100. At higher
      MOI, at least in vitro, P. gingivalis mediates endothelial apoptosis, thereby
      potentially amplifying proatherogenic mechanisms in the perturbed vasculature.

PMID- 17459113
TI  - Quorum sensing in Serratia.
AB  - Many bacteria use cell-cell communication to monitor their population density,
      synchronize their behaviour and socially interact. This communication results in
      a coordinated gene regulation and is generally called quorum sensing. In gram
      negative bacteria, the most common quorum signal molecules are acylated
      homoserine lactones (AHLs), although other low-molecular-mass signalling
      molecules have been described such as Autoinducer-2 (AI-2). The phenotypes that
      are regulated in Serratia species by means of AHLs are remarkably diverse and of
      profound biological and ecological significance, and often interconnected with
      other global regulators. Furthermore, AHL- and AI-2-mediated systems (less
      profoundly studied) are continuously being discovered and explored in Serratia
      spp., many having interesting twists on the basic theme. Therefore, this review
      will highlight the current known quorum sensing systems in Serratia spp.,
      including the important nosocomial pathogen Serratia marcescens.

PMID- 17459114
TI  - Regulation of the initiation of chromosomal replication in bacteria.
AB  - The initiation of chromosomal replication occurs only once during the cell cycle
      in both prokaryotes and eukaryotes. Initiation of chromosome replication is the
      first and tightly controlled step of a DNA synthesis. Bacterial chromosome
      replication is initiated at a single origin, oriC, by the initiator protein DnaA,
      which specifically interacts with 9-bp non-palindromic sequences (DnaA boxes) at
      oriC. In Escherichia coli, a model organism used to study the mechanism of DNA
      replication and its regulation, the control of initiation relies on a reduction
      of the availability and/or activity of the two key elements, DnaA and the oriC
      region. This review summarizes recent research into the regulatory mechanisms of
      the initiation of chromosomal replication in bacteria, with emphasis on organisms
      other than E. coli.

PMID- 17459115
TI  - A postgenomic view of the heat shock proteins in kinetoplastids.
AB  - The kinetoplastids Leishmania major, Trypanosoma brucei and Trypanosoma cruzi are
      causative agents of a diverse spectrum of human diseases: leishmaniasis, sleeping
      sickness and Chagas' disease, respectively. These protozoa possess digenetic life
      cycles that involve development in mammalian and insect hosts. It is generally
      accepted that temperature is a triggering factor of the developmental programme
      allowing the adaptation of the parasite to the mammalian conditions. The heat
      shock response is a general homeostatic mechanism that protects cells from the
      deleterious effects of environmental stresses, such as heat. This response is
      universal and includes the synthesis of the heat-shock proteins (HSPs). In this
      review, we summarize the salient features of the different HSP families and
      describe their main cellular functions. In parallel, we analyse the composition
      of these families in kinetoplastids according to literature data and our
      understanding of genome sequence data. The genome sequences of these parasites
      have been recently completed. The HSP families described here are: HSP110,
      HSP104, group I chaperonins, HSP90, HSP70, HSP40 and small HSPs. All these
      families are widely represented in these parasites. In particular, kinetoplastids
      possess an unprecedented number of members of the HSP70, HSP60 and HSP40
      families, suggesting key roles for these HSPs in their biology.

PMID- 17459116
TI  - Bond strength between fibre posts and composite resin cores: effect of post
      surface silanization.
AB  - AIM: To evaluate the tensile bond strength between two different composite resin
      cores and (Clearfil Core, MultiCore Flow) and fibre posts (DT Light Post), with
      and without silanization of the post surface. METHODOLOGY: Forty fibre posts were
      shortened to a length of 15 mm. Specimens were then produced by covering the
      upper 3 mm of the posts with standardized composite core build-ups. The bonding
      surfaces of twenty posts were treated with silane coupling agent (Monobond-S).
      Four experimental groups were formed: G1: Clearfil Core; G2: Monobond-S +
      Clearfil Core; G3: MultiCore Flow; G4: Monobond-S + MultiCore Flow. Each post was
      positioned upright in a post centric device with moulds to ensure standardized
      shapes of the abutments. After tensile bond strength testing, the type of failure
      at the interface was determined. The results obtained were compared using an
      unpaired sample t-test. RESULTS: The mean tensile bond strengths and standard
      deviations were [MPa] 10.08 +/- 0.92 for Clearfil Core, 10.47 +/- 1.05 for
      Clearfil Core + silane; 6.65 +/- 0.79 for MultiCore Flow and 6.91 +/- 0.83 for
      MultiCore Flow + silane. Statistical analysis revealed that Clearfil Core
      achieved significantly higher bond strengths than MultiCore Flow (P < 0.0001).
      Post silanization had no significant effect. All tested specimens had an adhesive
      failure mode. CONCLUSION: Type of composite had a significant effect on tensile
      bond strength. Silanization of fibre post surfaces had no effect on core
      retention.

PMID- 17459117
TI  - Low-cycle fatigue of NiTi rotary instruments of various cross-sectional shapes.
AB  - AIM: To compare the low-cycle fatigue (LCF) behaviour of some commercial NiTi
      instruments subjected to rotational bending, a deformation mode similar to an
      engine-file rotating in a curved root canal, using a strain-life analysis, in
      water. METHODOLOGY: A total of 286 NiTi rotary instruments from four
      manufacturers were constrained into a curvature by three rigid, stainless steel
      pins whilst rotating at a rate of 250 rpm in deionized water until broken. The
      number of revolutions was recorded using an optical counter and an electronic
      break-detection circuit. The surface strain amplitude, calculated from the
      curvature (from a photograph) and diameter of the fracture cross-section (from a
      scanning electron micrograph), was plotted against the number of cycles to
      fracture for each instrument. A regression line was fitted to the LCF lives for
      each brand; the value was compared with that of others using one-way analysis of
      variance (ANOVA). The number of crack origins observed on the fractographic view
      was examined with chi-square for differences amongst various groups. RESULTS: A
      linear strain-life relationship, on logarithmic scales, was obtained for the LCF
      region with an apparent fatigue-ductility exponent ranging from -0.40 to -0.56.
      The number of crack-initiation sites, as observed on the fracture cross-section,
      differed between brands (chi(2), P < 0.05), but not LCF life (one-way ANOVA, P >
      0.05). CONCLUSIONS: The LCF life of NiTi instruments declines with an inverse
      power function dependence on surface strain amplitude, but is not affected by the
      cross-sectional shape of the instrument.

PMID- 17459118
TI  - Leakage of food-borne Enterococcus faecalis through temporary fillings in a
      simulated oral environment.
AB  - AIM: To evaluate the hypothesis that food-borne viable Enterococcus faecalis
      cells could enter the root canal space via coronal leakage. METHODOLOGY: In a
      simulated oral environment under mastication the capacity of a calcium sulphate
      based temporary filling material (Cavit W) to prevent leakage of E. faecalis from
      a cheese through the endodontic access cavity into the pulp chamber was assessed.
      Standardized class I access cavities were prepared in human maxillary molars.
      These were filled with Cavit of either 2 or 4 mm thickness (n=16, each). Empty
      access cavities served as positive, teeth filled with a light-curing composite
      material acted as negative controls (n=8, each). A cheese containing viable E.
      faecalis cells was placed on the occlusal aspects of test and control teeth,
      which were subsequently subjected to 680 mastication loads per day for 1 week in
      a masticator device perfused with artificial saliva at 37 degrees C. Leakage of
      E. faecalis from the cheese into the pulp chamber was assessed by culture on a
      kanamycin aesculin azide agar and compared between groups using Fisher's exact
      test. RESULTS: All of the positive controls showed pure growth of E. faecalis. In
      addition, one of the negative control teeth leaked. The 4 mm application of Cavit
      prevented leakage of E. faecalis significantly better than the corresponding 2 mm
      application: 1 of 16 specimens compared with 6 of 16 specimens had leakage,
      respectively (P<0.05). CONCLUSIONS: The current results substantiate the
      suspicion that food-derived microbiota could enter the necrotic root canal system
      via microleakage.

PMID- 17459119
TI  - A comparative study of three periapical radiographic techniques for endodontic
      working length estimation.
AB  - AIM: To compare the diagnostic quality of endodontic working length estimation
      films produced using film holders with those taken using the bisecting angle
      technique and to assess the level of acceptance of film holders by operator and
      patient. METHODOLOGY: Five post-graduate and 20 final year undergraduate students
      attending a UK Dental School produced working length radiographs using either the
      paralleling or the bisecting angle technique. The paralleling group used one of
      two film holders, the Endoray II or the XCP Endodontic Instrument, on alternate
      patients. An assessment of the ease of use of the device and the patients' views
      on the comfort of the examination were recorded. Each radiograph was examined
      simultaneously by two assessors, scored for film faults and diagnostic
      acceptability. Statistical data was derived using the Mann-Whitney U test and
      Cohen's kappa. RESULTS: The rates of unacceptable radiographs for the XCP
      Endodontic Instrument, Endoray II and the bisecting angle techniques were 12.2%,
      21.4% and 48.6%, respectively. The combined percentage of unacceptable
      paralleling technique films (16.7%) was highly significantly different (P <
      0.001) when compared with the bisecting angle technique (48.6%). The paralleling
      technique produced a significant reduction in incorrect vertical angulation (P <
      0.001), cone cutting (P < 0.001) and incorrect film placement (P < 0.001). Film
      holders were rated either excellent or good in 90% of examinations by operators
      and 47.5% of patients reported no discomfort. CONCLUSIONS: These results support
      the use of the film holders for endodontic working length estimation.

PMID- 17459120
TI  - Hydration mechanisms of mineral trioxide aggregate.
AB  - AIM: To report the hydration mechanism of white mineral trioxide aggregate (White
      MTA, Dentsply, Tulsa Dental Products, Tulsa, OK, USA). METHODOLOGY: The chemical
      constitution of white MTA was studied by viewing the powder in polished sections
      under the scanning electron microscope (SEM). The hydration of both white MTA and
      white Portland cement (PC) was studied by characterizing cement hydrates viewed
      under the SEM, plotting atomic ratios, performing quantitative energy dispersive
      analyses with X-ray (EDAX) and by calculation of the amount of anhydrous clinker
      minerals using the Bogue calculation. RESULTS: Un-hydrated MTA was composed of
      impure tri-calcium and di-calcium silicate and bismuth oxide. The aluminate phase
      was scarce. On hydration the white PC produced a dense structure made up of
      calcium silicate hydrate, calcium hydroxide, monosulphate and ettringite as the
      main hydration products. The un-reacted cement grain was coated with a layer of
      hydrated cement. In contrast MTA produced a porous structure on hydration. Levels
      of ettringite and monosulphate were low. Bismuth oxide was present as un-reacted
      powder but also incorporated with the calcium silicate hydrate. CONCLUSIONS:
      White MTA was deficient in alumina suggesting that the material was not prepared
      in a rotary kiln. On hydration this affected the production of ettringite and
      monosulphate usually formed on hydration of PC. The bismuth affected the
      hydration mechanism of MTA; it formed part of the structure of C-S-H and also
      affected the precipitation of calcium hydroxide in the hydrated paste. The
      microstructure of hydrated MTA would likely be weaker when compared with that of
      PC.

PMID- 17459121
TI  - The effect of condensation pressure on selected physical properties of mineral
      trioxide aggregate.
AB  - AIM: To examine the effect of condensation pressure on surface hardness,
      microstructure and compressive strength of mineral trioxide aggregate (MTA).
      METHODOLOGY: White ProRoot MTA (Dentsply Tulsa Dental, Johnson City, TN, USA) was
      mixed and packed into cylindrical polycarbonate tubes. Six groups each of 10
      specimens were subjected to pressures of 0.06, 0.44, 1.68, 3.22, 4.46 and 8.88
      MPa respectively. The surface hardness of each specimen was measured using
      Vickers microhardness. Cylindrical specimens of 4 mm in diameter and 6 mm in
      height were prepared in polycarbonate cylindrical moulds for testing the
      compressive strength. Five groups of 10 specimens were prepared using pressures
      of 0.06, 0.44, 1.68, 3.22 or 4.46 MPa. Data were subjected to one-way anova. The
      microstructure was analysed using a scanning electron microscope (SEM) after
      sectioning specimens with a scalpel. RESULT: A trend was observed for higher
      condensation pressures to produce lower surface hardness values. A condensation
      pressure of 8.88 MPa produced specimens with significantly lower values in terms
      of surface hardness than other groups (P<0.001). A condensation pressure of 1.68
      MPa conferred the maximum compressive strength; however, it was not statistically
      different. Higher condensation pressures resulted in fewer voids and
      microchannels when analysed with SEM. In specimens prepared with lower
      condensation pressures distinctive crystalline structures were observed. They
      tended to appear around microchannels. CONCLUSION: Condensation pressure may
      affect the strength and hardness of MTA. Use of controlled condensation pressure
      in sample preparation for future studies is suggested.

PMID- 17459122
TI  - Testosterone decreased urinary-frequency in nNOS-deficient mice.
AB  - To observe the effect of testosterone on the frequency of urination in mice
      lacking neuronal nitric oxide synthase (nNOS(-/-)), we compared the urination
      patterns between unanaesthetized male wild-type (n = 27) and nNOS(-/-) mice (n =
      50) with or without testosterone treatment. Compared with wild-type mice, nNOS(-/
      ) mice showed a greater frequency of urination during a 24-h observation period
      (3.0 vs. 5.4 times/day, p < 0.0001) without any significant difference in the
      total voided volume or the functional voiding capacity. While testosterone
      treatment did not affect the urination patterns in wild-type, it decreased the
      daytime frequency of urination (5.4 vs. 3.7 times, p = 0.0198) and the nighttime
      urination (4.4 vs. 2.9 times, p = 0.039) in nNOS(-/-) mice. The nNOS(-/-) mice
      can be a useful animal model for urinary frequency. Testosterone improved the
      functional abnormalities in the voiding of nNOS(-/-) mice.

PMID- 17459123
TI  - Meiotic segregation analysis in male translocation carriers by using fluorescent
      in situ hybridization.
AB  - Balanced reciprocal and Robertsonian translocations are the most common
      structural chromosome abnormalities in humans, with incidences of 0.7 and 1.23
      per 1000. These translocations can affect fertility and/or pregnancy outcome
      because of possibly impaired production of gametes with an unbalanced zygote
      caused by the parental arrangement. Fertility problems in male translocation
      carriers are because of various degrees of sperm alterations that are directly
      related to the disturbance of the meiotic process. Investigation of human sperm
      chromosomes was performed by karyotyping spermatozoa after penetration of zona
      free hamster oocytes, karyotype analysis now being possible to analyse the
      segregation patterns by using fluorescent in situ hybridization (FISH). Here, we
      document the results of meiotic segregation analysis for four Robertsonian and
      four reciprocal translocation carriers by FISH. In the sperm of Robertsonian
      translocation males, the majority of spermatozoa were normal/balanced. On the
      other hand, males with reciprocal translocations demonstrated a high rate of
      unbalanced spermatozoa of about 50% on meiotic segregation, with an unusually
      high rate (23.5%) of 3 : 1 segregation. This knowledge can be used for genetic
      counselling of families with these types of translocations.

PMID- 17459124
TI  - Age at voice break in Danish boys: effects of pre-pubertal body mass index and
      secular trend.
AB  - Voice break is a late, but characteristic event in male puberty. Assessment of
      age at voice break may be a relevant marker for epidemiological studies of male
      pubertal development. We investigated the timing of voice break and its
      association with explanatory variables [calendar year of admission in the boys
      choir and pre-pubertal body mass index (BMI)] by survival analysis techniques
      based on retrospective analyses of age at voice break in 463 Danish choir boys
      who were studied over a 10-year period. We found an overall median age at voice
      break of 14.0 [13.9-14.6] years, and a statistically significant downwards trend
      in age at voice break in the 10-year period (1994-2003) (log-rank test p =
      0.0146). There was a statistically significant difference in age at voice break
      between boys in the different BMI quartiles in pre-puberty (p = 0.00822) with a
      tendency towards early voice break with increasing BMI standard deviation scores.
      Thus boys in the heaviest quartile at 8 years of age had an increased risk of
      early voice break (RR of 1.74 [1.14-2.65]) approximately 6 years later, compared
      with boys in the thinnest quartile. The earlier voice break seen during the 10
      year observation period could however not exclusively be explained by a general
      increase in BMI in that period. Our findings indicate that puberty, as assessed
      by age at voice break in boys, may be starting earlier in Denmark as it has been
      observed in the USA, and suggest a relationship between pre-pubertal BMI and the
      timing of puberty.

PMID- 17459125
TI  - Seminal factor VII and factor VIIa: supporting evidence for the presence of an
      active tissue factor-dependent coagulation pathway in human semen.
AB  - Human semen spontaneously coagulates into a semisolid mass and then wholly
      liquefies in a process that may have some similarity to that of normal blood.
      This well described phenomenon is referred to as coagulation and liquefaction of
      semen. Besides other active components of the haemostatic system, semen contains
      a significant amount of functional tissue factor (TF). However, TF needs factor
      (F)VII in order to exert it actions. In this study, we assessed human semen for
      the presence of FVII and FVIIa, and related their levels to conventional
      fertility parameters. Using a functional, one stage, clotting assay based upon
      the prolongation of the prothrombin clotting time, using the ACL 300R analyser
      and an Imubind FVIIa ELISA assay, FVII and FVIIa levels were measured in 97 semen
      specimens obtained from sub-fertile (sperm counts <20 x 10(6)/mL), normally
      fertile (sperm counts >or=20 x 10(6) but <60 x 10(6)/mL), fertile sperm donors
      (sperm counts >or=60 x 10(6)/mL), vasectomized subjects and in a pooled normal
      semen parameters group (categorization into groups was based on the World Health
      Organization guidelines on fertility criteria). In addition, conventional semen
      parameters were analysed on all semen samples. Both FVII and FVIIa were
      quantifiable in human semen. The mean levels of FVII and FVIIa were 4.4 IU/dL and
      12 ng/mL respectively. Despite the observed variations of FVIIa levels in the
      studied groups they did not meet statistical significance when the groups were
      tested against each other. However, seminal FVIIa levels showed a significant
      positive association with semen liquefaction time, sperm motility and semen
      volume. The anti-sperm antibodies and sperm-agglutination groups were also
      associated with raised seminal FVIIa levels. We observed no significant
      relationship between FVIIa levels and total sperm concentration, sperm count per
      mL (sperm density), sperm progression and days of sexual abstinence. This study
      demonstrates that human semen contains appreciable amounts of FVII and FVIIa. It
      is possible to quantify these using commercially available assays. There also
      appears to be a direct correlation between the levels of these factors and
      certain seminal parameters. This finding reinforces the concept of an active
      clotting system in human semen, by establishing the missing link in the
      activation of a TF-dependent pathway.

PMID- 17459126
TI  - Development of the role of public health nurses in addressing child and family
      poverty: a framework for action.
AB  - AIM: The purpose of this paper is to invite dialogue about how public health
      nurses could best address child and family poverty. Their current role is
      reviewed and a framework for expanding this role is presented. BACKGROUND: The
      negative health consequences of poverty for children are well-documented
      worldwide. The high levels of children living in poverty in wealthy
      industrialized countries such as Canada should be of concern to the health
      sector. What role(s) can public health nurses play in addressing child and family
      poverty? METHOD: A review of scholarly literature from Canada, the United States
      of America and the United Kingdom was conducted to ascertain support for public
      health nurses' roles in reducing poverty and its effects. We then reviewed
      professional standards and competencies for nursing practice in Canada. The data
      were collected between 2005 and 2006. FINDINGS: Numerous nursing scholars have
      called for public health nurses to address the causes and consequences of poverty
      through policy advocacy. However, this role was less likely to be identified in
      professional standards and competencies, and we found little empirical evidence
      documenting Canadian public health nurses' efforts to engage in this role. Public
      health nurses' roles in relation to poverty focus primarily on assisting families
      living in poverty to access appropriate services rather than directing efforts at
      the policy level. Factors associated with this limited involvement are
      identified. We suggest that the conceptual framework developed by Blackburn in
      the United Kingdom offers direction for a more fully developed public health
      nursing role. Prerequisites to engaging in the strategies articulated in the
      framework are discussed. CONCLUSION: Given more organizational support and
      enhanced knowledge and skills, public health nurses could be playing a greater
      role in working with others to make child and family poverty history.

PMID- 17459128
TI  - The challenges for nurses communicating with and gaining valid consent from
      adults with intellectual disabilities within the accident and emergency care
      service.
AB  - AIM: This paper reports the challenges experienced by nurses within accident and
      emergency departments in communicating with and gaining valid consent from adults
      with intellectual disabilities. BACKGROUND: Consent is both a legal requirement
      and an ethical principle required to be obtained by health-care professionals,
      prior to the start of any examination, treatment and/or care. Central to the
      process of seeking consent is effective communication. However, evidence shows
      that people with intellectual disabilities are not viewed by professionals within
      acute general hospitals as a vital source of information, neither are they often
      communicated with directly, nor involved in discussions or decisions about their
      health care and are frequently not directly asked for their consent. METHOD: A
      purposive sample of nurses working within the accident and emergency departments
      of five general hospitals was recruited to participate in this qualitative study.
      Data were collected from five focus groups. FINDINGS: Effective communication was
      identified as the most challenging aspect in caring for adults with intellectual
      disabilities within this environment, having an impact on the assessment of
      needs, informing patients of their health status and seeking valid consent.
      CONCLUSIONS: Fundamental to the provision of quality care are the concepts
      communication, choice and control. However, these issues are perceived to be more
      challenging in the provision of health care to people with intellectual
      disabilities. Communication and consent, therefore, require further consideration
      within the educational and clinical areas to strengthen nurses' competence in
      caring for people with intellectual disabilities, with an emphasis and
      understanding that choice and control are key principles for all people, being
      central aspects to the provision of an inclusive service for people with
      intellectual disabilities. RELEVANCE TO CLINICAL PRACTICE: All nurses need to
      have a greater awareness of learning disability, how to increase opportunities
      for effective communication and be very familiar with the issue and guidelines
      relating to consent, to ensure that people with learning disabilities have
      choice, control and are more active in decision making regarding their health.

PMID- 17459131
TI  - Clinical validation of the signs and symptoms and the nature of the respiratory
      nursing diagnoses in patients under invasive mechanical ventilation.
AB  - AIMS: The aims of this study were to validate the signs and symptoms of the
      respiratory nursing diagnoses impaired gas exchange, ineffective airway clearance
      and ineffective breathing pattern in patients under mechanical ventilation; to
      verify whether intubation time and ventilatory modalities were related factors
      for respiratory nursing diagnoses; to verify the occurrence of shared signs and
      symptoms in the diagnoses and compare them with North American Nursing Diagnosis
      Association's proposition and to ascertain whether respiratory nursing diagnoses
      occur in isolated or associated patterns. BACKGROUND: The need for mechanical
      ventilation is common in several patients admitted to intensive care units.
      Therefore, critical care nurses should identify the respiratory nursing diagnoses
      of high incidence. DESIGN AND METHODS: Descriptive observational study, with 177
      evaluations of surgical and medical critically ill adult patients undergoing
      invasive mechanical ventilation. The study adopted Fehring's Modified Clinical
      Diagnostic Validity Model, with a suggested alteration. RESULTS: The critical
      signs and symptoms were the same as proposed by North American Nursing Diagnosis
      Association, when the diagnoses were separately identified, although no
      particular sign and symptom was found for ineffective breathing pattern. Impaired
      gas exchange and ineffective airway clearance were identified as having 88
      (49.7%) evaluations sharing the critical signs and symptoms. Intubation time and
      ventilation modality were related factors for the development of ineffective
      airway clearance and ineffective breathing pattern. CONCLUSION: The critical
      signs and symptoms of impaired gas exchange were abnormal blood gases and
      hypoxemia. For ineffective airway clearance, they were rhonchi and decreased
      breath sounds. No highlights were found for ineffective breathing pattern signs
      and symptoms. Validation by experts has confirmed these findings. The interface
      between ineffective airway clearance and impaired gas exchange was confirmed by
      the presence of the shared critical signs and symptoms. RELEVANCE TO CLINICAL
      PRACTICE: Studies like this are relevant to clinical practice because they
      evaluate the adequacy of Taxonomy II for patients under mechanical ventilation in
      clinical practice, thus allowing for the intensive care nurses to go from one
      mechanical and routine practice to a critical, reflexive practice, committed to
      professional progress.

PMID- 17459132
TI  - Stoma coloproctology nurse specialist: a case study.
AB  - AIMS AND OBJECTIVES: The aim of this paper is to provide insight into the role of
      a Stoma Coloproctology Nurse Specialist. This paper presents the findings of an
      in-depth case study of a stoma coloproctology nurse specialist employed in one
      health board area in Northern Ireland. This case study was part of a larger study
      exploring innovative nursing and midwifery roles in Northern Ireland. BACKGROUND:
      Specialist nursing roles have evolved and developed in response to changing
      health care needs, patient expectations, changes in professional regulation and
      government initiatives. DESIGN: A case study approach was adopted. METHOD: Semi
      structured interviews with the post holder (PH), her line manager and the human
      resource manager were undertaken. Non-participant observation of the PH's
      practice was also carried out. Analysis was undertaken on secondary data such as
      job specification, annual reports and other documentation relating to the post.
      RESULTS: Findings illustrate the PH's function and the impact of the role on
      patient care. Examples of innovative practices relating to providing care,
      support and guidance for patients and their families were identified; however,
      limitations to her role were also identified. CONCLUSIONS: The PH provides an
      invaluable service to patients, demonstrating a positive impact on care. However,
      the findings suggest the importance of establishing clear role boundaries, which
      may lead to professional growth and practice development. RELEVANCE TO CLINICAL
      PRACTICE: Although this study provides a valuable insight into the role of a
      Stoma Coloproctology Nurse Specialist a number of challenges exist, as the CNS
      role requires policy and appropriate educational preparation to practice at an
      advanced level. Further research investigating the development of the CNS role in
      the clinical setting and its relationship to members of the multi-professional
      team would be beneficial.

PMID- 17459135
TI  - Deliberate self-harm: emergency department nurses' attitudes, triage and care
      intentions.
AB  - AIM AND OBJECTIVES: This exploratory study investigates emergency department
      nurses' attitudes towards patients who engage in deliberate self-harm. It
      examines their attitudes towards, and triage and care decisions with, patients
      who self-harm. BACKGROUND: Emergency department nurses sometimes show
      unsympathetic attitudes towards patients who present with self-harm and these can
      contribute to difficulties in assessing and providing appropriate care. DESIGN: A
      modified version of the Suicide Opinion Questionnaire was used. A non-probability
      sample of 43 emergency department nurses from a large Australian hospital
      participated in the study. Data were analysed using SPSS. RESULTS: Most nurses
      had received no educational preparation to care for patients with self-harm; over
      20% claimed that the department either had no practice guidelines for deliberate
      self-harm or they did not know of their existence and one-third who knew of them
      had not read them. Overall, nurses had sympathetic attitudes towards patients who
      self-harm, including both professional and lay conceptualizations of deliberate
      self-harm. They did not discriminate against this group of patients in their
      triage and care decisions. CONCLUSIONS: The findings of this exploratory study
      are important because attitudes can affect care decisions. Recommendations are
      made for improving the educational preparation of emergency department nurses,
      for improving awareness and implementation of practice guidelines, and for
      improving attitudes towards patients with deliberate self-harm. Further research
      is needed to confirm these results.

PMID- 17459137
TI  - A comparison of sleep assessment tools by nurses and patients in critical care.
AB  - AIM: The aim of this critical care sleep assessment pilot study was to evaluate
      the usefulness of three sleep assessment tools to identify which, if any,
      provided the closest comparison between the nurses' judgement and the patients'
      experience of their sleep. The study objectives were to: (i) compare patients'
      and nurses' assessment of sleep using three different rating tools. (ii)
      Ascertain patients' preferences with non-interventional, user friendly, practical
      tools in critical care. (iii) Recommend changes and improvements to the way that
      sleep is assessed and documented. BACKGROUND: Sleep is important for promoting
      critical care recovery and sleep disturbance is known to cause irritability,
      aggression and increased stress levels. The availability and use of valid
      critical care sleep assessment tools is limited. DESIGN: A descriptive
      comparative study using three sleep assessment-rating scales were constructed to
      provide easy to understand tools for completion by both patients and nurses in
      critical care. METHODS: Structured interviews were undertaken with 82 patients
      and 82 nurses using a convenience sample from four multispecialty critical care
      units in one large teaching trust. Patients were included in the study if they
      met a list of pre-defined criteria to obtain responses from lucid orientated
      patients. RESULTS: No tool produced a close association between the nurses'
      assessment of the patients sleep and the patients' assessment of their sleep.
      Patients found two of the three tools easy to use when rating their sleep.
      Discussion. Objective invasive measurements of sleep as well as complex
      subjective tools appear inappropriate to be used as a part of daily critical care
      practice. The application of simple rating scores has a high degree of error when
      nurses assess patients' sleep, even though high levels of patient observation and
      assessment are practiced in critical care. CONCLUSIONS: More research is needed
      to examine the assessment of sleep in critical care, particularly linking rating
      scales to alternative methods of physiological assessment of sleep. Findings
      indicate nurses are unable to accurately assess critical care patients' sleep
      using rating assessment tools. However patients were found to prefer two sleep
      assessment tools, one banded in hours to assess sleep quantity and one as a
      comparison against normal sleep to assess sleep quality. RELEVANCE TO CLINICAL
      PRACTICE: This study reviews the importance of sleep assessment and the diverse
      methods available for assessing sleep focussing on the critically ill patient.
      More noteworthy it highlights how nurses sole judgements of patients sleep is not
      a reliable method in clinical practice, however it provides some indication on
      the application of 'easy to use' tools to assist in the patients assessments of
      their sleep.

PMID- 17459138
TI  - Close relatives in intensive care from the perspective of critical care nurses.
AB  - AIM: The aim was to describe critical care nurses' experiences of close relatives
      within intensive care. BACKGROUND: There is a lack of research describing
      critical care nurses' experiences of the significance of close relatives in
      intensive care. Knowledge in this area will support critical care nurses to
      develop good nursing care for the critically ill person and their close
      relatives. DESIGN AND METHOD: The design of the study was qualitative. Data
      collection was carried out through focus group discussions with 24 critical care
      nurses in four focus groups during spring 2004. The data were subjected to
      qualitative thematic content analysis. RESULTS: The focus groups discussions
      showed that the presence of close relatives was taken for granted by critical
      care nurses and it was frustrating if the critically ill person did not have any.
      Information from close relatives made it possible for critical care nurses to
      create individual care for the critically ill person. They supported close
      relatives by giving them information, being near and trying to establish good
      relations with them. Close relatives were important. Critical care nurses lacked
      forums for reflection and discussion about the care given. RELEVANCE TO CLINICAL
      PRACTICE: This study indicates that close relatives are a prerequisite for
      critical care nurses to give good nursing care to meet the needs of the
      critically ill person. A communication based on mutual understanding is necessary
      if critical care nurses are to be able to support close relatives. Dealing
      constantly with situations that were ethically difficult without any chance to
      reflect was an obstacle for critical care nurses to improve their work with close
      relatives.

PMID- 17459139
TI  - Implementation of nurse-delivered vestibular rehabilitation in primary care: a
      qualitative study of nurses' views on involvement in an innovative service.
AB  - AIM: To explore practice nurses' perceptions of vestibular rehabilitation and its
      place in relation to their general role development. BACKGROUND: Vestibular
      rehabilitation has been known for a long time to be effective for chronically
      dizzy patients in secondary care, but its use in primary care has been limited. A
      recent pragmatic trial of vestibular rehabilitation delivered by practice nurses
      in primary care has confirmed its utility in a community setting. This type of
      role is increasingly common for practice nurses, but few studies explore the
      nurses' perspective. METHODS: A qualitative study was undertaken; 19 nurses took
      part in focus group sessions. Participants discussed their views on vestibular
      rehabilitation and its potential for integration with their existing role. A
      thematic analysis of the data was undertaken. FINDINGS: Four main themes were
      identified: creating a unique nursing role; the therapeutic role; responsibility
      and role boundaries; and time. Nurses were positive about developing extended
      roles, but sought ways to achieve this without eroding fundamental nursing
      skills. Vestibular rehabilitation was seen as fulfilling both the need for a
      distinct nursing identity and professional development. Concerns over
      responsibility for patient assessment and time management constraints are
      potential obstacles to overcome in the wider development of this therapy in
      primary care. CONCLUSIONS: Understanding the perspective of nurses will be vital
      in future development of chronic disease management within primary care. Whilst
      nurses may be positive about such role expansion, the implementation of services
      of this type will require clarity about nurses' responsibilities and flexibility
      in managing workload. RELEVANCE TO CLINICAL PRACTICE: Vestibular rehabilitation
      is simple, low-tech and appropriate for widespread development in primary care.
      Nurses wishing to provide vestibular rehabilitation or similar chronic disease
      management activities will need to work with medical colleagues to define role
      boundaries.

PMID- 17459141
TI  - Well-being of institutionalized elders after Yang-style Tai Chi practice.

PMID- 17459142
TI  - The effects of muscular dystrophy on the craniofacial shape of Mus musculus.
AB  - Skeletal anomalies are common in patients with muscular dystrophy, despite an
      absence of mutations to genes that specifically direct skeletogenesis. In order
      to understand these anomalies further, we examined two strains of muscular
      dystrophy (laminin- and merosin-deficient) relative to controls, to determine how
      the weakened muscle forces affected skull shape in a mouse model. Shape was
      characterized with geometric morphometric techniques, improving upon the limited
      analytical power of the standard linear measurements. Through these techniques,
      we document the specific types of cranial skeletal deformation produced by the
      two strains, each with individual shape abnormalities. The mice with merosin
      deficiency (with an earlier age of onset) developed skulls with more deformation,
      probably related to the earlier ontogenetic timing of disease onset. Future
      examinations of these mouse models may provide insight regarding the impact of
      muscular forces and the production and maintenance of craniofacial integration
      and modularity.

PMID- 17459143
TI  - Morphological and physiological interactions of NG2-glia with astrocytes and
      neurons.
AB  - Models of central nervous system (CNS) function have historically been based on
      neurons and their synaptic contacts - the neuronal doctrine. This doctrine
      envisages glia as passive supportive cells. However, electrophysiological and
      imaging studies in brain slices show us that astrocytes, the most numerous cells
      in the brain, express a wide range of neurotransmitter receptors that are
      activated in response to synaptic activity. Furthermore, astrocytes communicate
      via calcium signals that are propagated over long distances by the release of
      'gliotransmitters', the most abundant being adenosine triphosphate (ATP). This
      has led to the concept of the neuron-astroglial functional unit as the substrate
      of integration in the CNS. Recently, a novel glial cell type has been
      characterized by expression of the proteoglycan NG2. These NG2-glia receive
      presynaptic input from neurons and responds to neurotransmitters released at
      synapses. Now, studies on transgenic mice in which fluorescent proteins are
      specifically expressed by subclasses of glia are helping to address the question
      of where NG2-glia fit in the neuron-astroglial model of integrated brain
      function. NG2-glia, as well as astrocytes, have been shown to respond to neuronal
      and astroglial signals by raised intracellular calcium, which is a potential
      communications mechanism by which NG2-glia may be active partners in neuron-glial
      circuits. Moreover, a current concept of NG2-glia considers them to be 'neural
      stem cells' and an exciting prospect is that neuron-glial signalling may regulate
      the differentiation capacity of NG2-glia and their response to injury.

PMID- 17459144
TI  - Brain pyruvate recycling and peripheral metabolism: an NMR analysis ex vivo of
      acetate and glucose metabolism in the rat.
AB  - The occurrence of pyruvate recycling in the rat brain was studied in either
      pentobarbital anesthetized animals or awake animals receiving a light analgesic
      dose of morphine, which were infused with either [1-13C]glucose + acetate or
      glucose + [2-13C]acetate for various periods of time. Metabolite enrichments in
      the brain, blood and the liver were determined from NMR analyses of tissue
      extracts. They indicated that: (i) Pyruvate recycling was revealed in the brain
      of both the anesthetized and awake animals, as well as from lactate and alanine
      enrichments as from glutamate isotopomer composition, but only after infusion of
      glucose + [2-13C]acetate. (ii) Brain glucose was labelled from [2-13C]acetate at
      the same level in anaesthetized and awake rats (approximately 4%). Comparing its
      enrichment with that of blood and liver glucose indicated that brain glucose
      labelling resulted from hepatic gluconeogenesis. (iii) Analysing glucose 13C-13C
      coupling in the brain, blood and the liver confirmed that brain glucose could be
      labelled in the liver through the activities of both pyruvate recycling and
      gluconeogenesis. (iv) The rate of appearance and the amount of brain glutamate C4
      C5 coupling, a marker of pyruvate recycling when starting from [2-13C]acetate,
      were lower than those of brain glucose labelling from hepatic metabolism. (v) The
      evaluation of the contributions of glucose and acetate to glutamate metabolism
      revealed that more than 60% of brain glutamate was synthesized from glucose
      whereas only 7% was from acetate and that glutamate C4-C5 coupling was mainly due
      to the metabolism of glucose labelled through hepatic gluconeogenesis. All these
      results indicate that, under the present conditions, the pyruvate recycling
      observed through the labelling of brain metabolites mainly originates from
      peripheral metabolism.

PMID- 17459145
TI  - Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated
      oral administration of rotenone is prevented by 4-phenylbutyrate, a chemical
      chaperone.
AB  - Parkinson's disease (PD) is a progressive neurodegenerative disorder that is
      primarily characterized by the degeneration of dopaminergic neurons in the
      nigrostriatal pathway. Previous studies have demonstrated that chronic systemic
      exposure of Lewis rats to rotenone produced many features of PD, and cerebral
      tauopathy was also detected in the case of severe weight loss. The present study
      was designed to assess the neurotoxicity of rotenone after daily oral
      administration for 28 days at several doses in C57BL/6 mice. In addition, we
      examined the protective effects of 4-phenylbutyrate (4-PBA) on nigral dopamine
      (DA) neurons in rotenone-treated mice. 4-PBA was injected intraperitoneally daily
      30 min before each oral administration of rotenone. Chronic oral administration
      of rotenone at high doses induced specific nigrostriatal DA neurodegeneration,
      motor deficits and the up-regulation of alpha-synuclein in the surviving DA
      neurons. In contrast to the Lewis rat model, cerebral tauopathy was not detected
      in this mouse model. 4-PBA inhibited rotenone-induced neuronal death and
      decreased the protein level of alpha-synuclein. These results suggest that this
      rotenone mouse model may be useful for understanding the mechanism of DA
      neurodegeneration in PD, and that 4-PBA has a neuroprotective effect in the
      treatment of PD.

PMID- 17459146
TI  - Formation of cellular projections in neural progenitor cells depends on SK3
      channel activity.
AB  - Ion channels are potent modulators for developmental processes in progenitor
      cells. In a screening approach for different ion channels in neural progenitor
      cells (NPCs) we observed a 1-ethyl-2-benzimidazolinone (1-EBIO) activated inward
      current, which could be blocked by scyllatoxin (ScTX, IC50=2+/- 0.3 nmol/L). This
      initial evidence for the expression of the small conductance Ca2+ activated K+
      channel SK3 was confirmed by the detection of SK3 transcripts and protein in
      NPCs. Interestingly, SK3 proteins were highly expressed in non-differentiated
      NPCs with a focused localization in lamellipodia as well as filopodial
      structures. The activation of SK3 channels using 1-EBIO lead to an immediate
      filopodial sprouting and the translocation of the protein into these novel
      filopodial protrusions. Both effects could be prevented by the pre-incubation of
      NPCs with ScTX. Our study gives first evidence that the formation and
      prolongation of filopodia in NPCs is, at least in part, effectively induced and
      regulated by SK3 channels.

PMID- 17459147
TI  - Temporal and mechanistic dissociation of ATP and adenosine release during
      ischaemia in the mammalian hippocampus.
AB  - Adenosine is well known to be released during cerebral metabolic stress and is
      believed to be neuroprotective. ATP release under similar circumstances has been
      much less studied. We have now used biosensors to measure and compare in real
      time the release of ATP and adenosine during in vitro ischaemia in hippocampal
      slices. ATP release only occurred following the anoxic depolarisation, whereas
      adenosine release was apparent almost immediately after the onset of ischaemia.
      ATP release required extracellular Ca2+. By contrast adenosine release was
      enhanced by removal of extracellular Ca2+, whilst TTX had no effect on either ATP
      release or adenosine release. Blockade of ionotropic glutamate receptors
      substantially enhanced ATP release, but had only a modest effect on adenosine
      release. Carbenoxolone, an inhibitor of gap junction hemichannels, also greatly
      enhanced ischaemic ATP release, but had little effect on adenosine release. The
      ecto-ATPase inhibitor ARL 67156, whilst modestly enhancing the ATP signal
      detected during ischaemia, had no effect on adenosine release. Adenosine release
      during ischaemia was reduced by pretreatment with homosysteine thiolactone
      suggesting an intracellular origin. Adenosine transport inhibitors did not
      inhibit adenosine release, but instead they caused a twofold increase of release.
      Our data suggest that ATP and adenosine release during ischaemia are for the most
      part independent processes with distinct underlying mechanisms. These two purines
      will consequently confer temporally distinct influences on neuronal and glial
      function in the ischaemic brain.

PMID- 17459148
TI  - A third-generation microsatellite-based linkage map of the honey bee, Apis
      mellifera, and its comparison with the sequence-based physical map.
AB  - BACKGROUND: The honey bee is a key model for social behavior and this feature led
      to the selection of the species for genome sequencing. A genetic map is a
      necessary companion to the sequence. In addition, because there was originally no
      physical map for the honey bee genome project, a meiotic map was the only
      resource for organizing the sequence assembly on the chromosomes. RESULTS: We
      present the genetic (meiotic) map here and describe the main features that
      emerged from comparison with the sequence-based physical map. The genetic map of
      the honey bee is saturated and the chromosomes are oriented from the centromeric
      to the telomeric regions. The map is based on 2,008 markers and is about 40
      Morgans (M) long, resulting in a marker density of one every 2.05 centiMorgans
      (cM). For the 186 megabases (Mb) of the genome mapped and assembled, this
      corresponds to a very high average recombination rate of 22.04 cM/Mb. Honey bee
      meiosis shows a relatively homogeneous recombination rate along and across
      chromosomes, as well as within and between individuals. Interference is higher
      than inferred from the Kosambi function of distance. In addition, numerous
      recombination hotspots are dispersed over the genome. CONCLUSION: The very large
      genetic length of the honey bee genome, its small physical size and an almost
      complete genome sequence with a relatively low number of genes suggest a very
      promising future for association mapping in the honey bee, particularly as the
      existence of haploid males allows easy bulk segregant analysis.

PMID- 17459149
TI  - Protecting exons from deleterious R-loops: a potential advantage of having
      introns.
AB  - BACKGROUND: Accumulating evidence indicates that the nascent RNA can invade and
      pair with one strand of DNA, forming an R-loop structure that threatens the
      stability of the genome. In addition, the cost and benefit of introns are still
      in debate. RESULTS: At least three factors are likely required for the R-loop
      formation: 1) sequence complementarity between the nascent RNA and the target
      DNA, 2) spatial juxtaposition between the nascent RNA and the template DNA, and
      3) accessibility of the template DNA and the nascent RNA. The removal of introns
      from pre-mRNA reduces the complementarity between RNA and the template DNA and
      avoids the spatial juxtaposition between the nascent RNA and the template DNA. In
      addition, the secondary structures of group I and group II introns may act as
      spatial obstacles for the formation of R-loops between nearby exons and the
      genomic DNA. CONCLUSION: Organisms may benefit from introns by avoiding
      deleterious R-loops. The potential contribution of this benefit in driving intron
      evolution is discussed. I propose that additional RNA polymerases may inhibit R
      loop formation between preceding nascent RNA and the template DNA. This idea
      leads to a testable prediction: intermittently transcribed genes and genes with
      frequently prolonged transcription should have higher intron density.

PMID- 17459150
TI  - GPs' use of problem solving therapy for depression: a qualitative study of
      barriers to and enablers of evidence based care.
AB  - BACKGROUND: Depression is a major health concern, predominantly treated by
      general practitioners (GPs). Problem solving therapy (PST) is recognised as an
      effective treatment for depression that is not widely used by GPs. This research
      aims to explore barriers and enablers that may influence GPs use of this
      treatment. METHOD: Qualitative methodology was used including individual and
      focus group interviews of GPs, PST experts and consumers. Analysis was undertaken
      using the Theory of Planned Behaviour (TPB) as a framework. RESULTS: A spectrum
      of potential influences, on GPs' use of PST emerged. Both barriers and enablers
      were identified. PST was perceived as being close to current practice approaches
      and potentially beneficial to both doctor and patient. In addition to a broadly
      positive attitude to PST, expressed by those with previous experience of its use,
      potential solutions to perceived barriers emerged. By contrast some GPs expressed
      fear that the use of PST would result in loss of doctor control of consultations
      and associated potential adverse patient outcomes. Patient expectations, which
      emerged as not always coinciding with GPs' perception of those expectations, were
      identified as a potential influence on GPs' decision concerning adoption of PST.
      In addition specific factors, including GP skill and confidence, consultation
      time constraints and technical issues related to PST were noted as potential
      concerns. CONCLUSION: This research contributes to our knowledge of the factors
      that may influence GPs' decisions regarding use of PST as a treatment for
      depression. It recognises both barriers and enablers. It suggests that for many
      GPs, PST is viewed in a positive light, providing encouragement to those seeking
      to increase the provision of PST by GPs. In identifying a number of potential
      barriers, along with associated options to address many of these barriers, it
      provides insights which may assist in the planning of GP training in PST.

PMID- 17459151
TI  - Interaction between ATM and PARP-1 in response to DNA damage and sensitization of
      ATM deficient cells through PARP inhibition.
AB  - ATM and PARP-1 are two of the most important players in the cell's response to
      DNA damage. PARP-1 and ATM recognize and bound to both single and double strand
      DNA breaks in response to different triggers. Here we report that ATM and PARP-1
      form a molecular complex in vivo in undamaged cells and this association
      increases after gamma-irradiation. ATM is also modified by PARP-1 during DNA
      damage. We have also evaluated the impact of PARP-1 absence or inhibition on ATM
      kinase activity and have found that while PARP-1 deficient cells display a
      defective ATM-kinase activity and reduced gamma-H2AX foci formation in response
      to gamma-irradiation, PARP inhibition on itself is able to activate ATM-kinase.
      PARP inhibition induced gamma H2AX foci accumulation, in an ATM-dependent manner.
      Inhibition of PARP also induces DNA double strand breaks which were dependent on
      the presence of ATM. As consequence ATM deficient cells display an increased
      sensitivity to PARP inhibition. In summary our results show that while PARP-1 is
      needed in the response of ATM to gamma irradiation, the inhibition of PARP
      induces DNA double strand breaks (which are resolved in and ATM-dependent
      pathway) and activates ATM kinase.

PMID- 17459152
TI  - A multimodality localization technique for radio-guided surgery.
AB  - BACKGROUND: Intraoperative localization of image or endoscopy-detected lesions
      occasionally pose surgical challenges due to the small lesion size and/or
      difficult anatomic exposure. Identification of such lesions can be facilitated
      using a hand-held gamma probe with utilization of Tc-99m macroaggregate albumen
      (MAA) localization technique. The radiopharmaceutical injection can be performed
      using ultrasound (US) or endoscopy guidance. CASE PRESENTATIONS: The clinical use
      of the Tc-99m MAA protocol gamma probe-guided surgery was discussed in three
      representative cases. Surgical indication was diagnostic exploration in two
      patients with suspicious lymphadenopathy, and determination of extent of surgical
      resection in a patient with polyposis. Lesion localization with 100 microcurie
      (3.7 MBq) Tc-99m MAA prior to surgical exploration resulted in definitive
      localization of lesions intraoperatively. CONCLUSION: The use Tc-99m MAA
      deposition technique at the site of surgical target is a highly efficient radio
      guided surgery technique with definitive impact on the success of surgical
      exploration in selected indications.

PMID- 17459153
TI  - Investigating health system performance: an application of data envelopment
      analysis to Zambian hospitals.
AB  - BACKGROUND: Zambia has recently articulated an ambitious national health program
      designed to meeting health-related MDGs. Public expectations are high and Zambia
      continues to receive significant resources from global and bilateral donors to
      support its health agenda. Although the lack of adequate resources presents the
      most important constraint, the efficiency with which available resources are
      being utilised is another challenge that cannot be overlooked. Inefficiency in
      producing health care undermines the service coverage potential of the health
      system. This paper estimates the technical efficiency of a sample of hospitals in
      Zambia. METHODS: Efficiency is measured using a DEA model. Vectors of hospital
      inputs and outputs, representing hospital expended resources and output profiles
      respectively, were specified and measured. The data were gathered from a sample
      of 30 hospitals throughout Zambia. The model estimates an efficiency score for
      each hospital. A decomposition of technical efficiency into scale and congestion
      is also provided. RESULTS: Results show that overall Zambian hospitals are
      operating at 67% level of efficiency, implying that significant resources are
      being wasted. Only 40% of hospitals were efficient in relative terms. The study
      further reveals that the size of hospitals is a major source of inefficiency.
      Input congestion is also found to be a source of hospital inefficiency.
      CONCLUSION: This study has demonstrated that inefficiency of resource use in
      hospitals is significant. Policy attention is drawn to unsuitable hospital scale
      of operation and low productivity of some inputs as factors that reinforce each
      other to make Zambian hospitals technically inefficient at producing and
      delivering services. It is argued that such evidence of substantial inefficiency
      would undermine Zambia's prospects of achieving its health goals.

PMID- 17459154
TI  - Gender distribution of adult patients on highly active antiretroviral therapy
      (HAART) in Southern Africa: a systematic review.
AB  - BACKGROUND: HIV and AIDS are significant and growing public health concerns in
      southern Africa. The majority of countries in the region have national adult HIV
      prevalence estimates exceeding 10 percent. The increasing availability of highly
      active antiretroviral therapy (HAART) has potential to mitigate the situation.
      There is however concern that women may experience more barriers in accessing
      treatment programs than men. METHODS: A systematic review of the literature was
      carried out to describe the gender distribution of patients accessing highly
      active antiretroviral therapy (HAART) in Southern Africa. Data on number of
      patients on treatment, their mean or median age and gender were obtained and
      compared across studies and reports. RESULTS: The median or mean age of patients
      in the studies ranged from 33 to 39 years. While female to male HIV infection
      prevalence ratios in the southern African countries ranged from 1.2:1 to 1.6:1,
      female to male ratios on HAART ranged from 0.8: 1 to 2.3: 1. The majority of the
      reports had female: male ratio in treatment exceeding 1.6. Overall, there were
      more females on HAART than there were males and this was not solely explained by
      the higher HIV prevalence among females compared to males. CONCLUSION: In most
      Southern African countries, proportionally more females are on HIV antiretroviral
      treatment than men, even when the higher HIV infection prevalence in females is
      accounted for. There is need to identify the factors that are facilitating
      women's accessibility to HIV treatment. As more patients access HAART in the
      region, it will be important to continue assessing the gender distribution of
      patients on HAART.

PMID- 17459155
TI  - Mediastinal extension of a complicated pancreatic pseudocyst; a case report and
      literature review.
AB  - BACKGROUND: Mediastinal pancreatic pseudocyst is a rare complication of acute or
      chronic pancreatitis. CASE PRESENTATION: This case report describes the
      management of a difficult case of pancreatic pseudocyst with a mediastinal
      extension in a patient having chronic pancreatitis. Different management
      strategies were used until complete resolution of this complex pseudocyst
      occurred using open surgical cystogastrostomy. CONCLUSION: Despite the
      availablity of different minimally invasive techniques to treat pancreatic
      pseudocysts, management of complex mediastinal pseudocyst may still require open
      surgical drainage procedures.

PMID- 17459156
TI  - Inward currents induced by ischemia in rat spinal cord dorsal horn neurons.
AB  - Hypoxia and ischemia occur in the spinal cord when blood vessels of the spinal
      cord are compressed under pathological conditions such as spinal stenosis,
      tumors, and traumatic spinal injury. Here by using spinal cord slice preparations
      and patch-clamp recordings we investigated the influence of an ischemia
      simulating medium on dorsal horn neurons in deep lamina, a region that plays a
      significant role in sensory hypersensitivity and pathological pain. We found that
      the ischemia-simulating medium induced large inward currents in dorsal horn
      neurons recorded. The onset of the ischemia-induced inward currents was age
      dependent, being onset earlier in older animals. Increases of sensory input by
      the stimulation of afferent fibers with electrical impulses or by capsaicin
      significantly speeded up the onset of the ischemia-induced inward currents. The
      ischemia-induced inward currents were abolished by the glutamate receptor
      antagonists CNQX (20 microM) and APV (50 microM). The ischemia-induced inward
      currents were also substantially inhibited by the glutamate transporter inhibitor
      TBOA (100 microM). Our results suggest that ischemia caused reversal operation of
      glutamate transporters, leading to the release of glutamate via glutamate
      transporters and the subsequent activation of glutamate receptors in the spinal
      dorsal horn neurons.

PMID- 17459157
TI  - Glomerulocystic kidney disease and its rare associations: an autopsy report of
      two unrelated cases.
AB  - BACKGROUND: Glomerulocystic kidney disease is an uncommon type of cystic renal
      disease. It is characterized by cortical microsysts, which are represented by
      cystic dilatation of Bowman's spaces. CASE PRESENTATION: We describe a case of
      glomerulocystic disease in a neonate and another in an abortus associated with
      tracheo-oesophageal fistula and megacystic-megaureter syndrome. The kidney on
      autopsy was sponge-like and revealed presence of cysts corresponding to
      dilatations of Bowman's space microscopically. In these two cases, the
      Glomerulocystic Kidney Disease in one case corresponded to a sporadic form and,
      in the other, to a syndromic, non-heritable form of glomerulocystic kidney
      disease. CONCLUSION: The associated anomalies in Glomerulocystic Kidney disease
      are well described in the literature. Two more new unrelated associations are
      described in this article.

PMID- 17459158
TI  - Superior epigastric artery pseudoaneurysm--a rare complication of chest drain
      insertion in coronary artery bypass grafting.
AB  - BACKGROUND: Although chest drain insertion during coronary artery bypass grafting
      is a fairly standard procedure, however it may result in extremely rare
      complications. CASE PRESENTATION: This is the first case being reported that
      demonstrates a pseudoaneurysm of superior epigastric artery resulting from chest
      drain insertion following coronary artery bypass grafting. CONCLUSION: Adequate
      caution should be used along with good understanding of the anatomical landmarks
      during apparently simple and standard operative procedures.

PMID- 17459160
TI  - Hyperglycemia alters enzyme activity and cell number in spinal sensory ganglia.
AB  - Peripheral sensory diabetic neuropathy is characterized by morphological,
      electrophysiological and neurochemical changes to a subpopulation of primary
      afferent neurons. Here, we utilized a transgenic mouse model of diabetes (OVE26)
      and age-matched controls to histologically examine the effect of chronic
      hyperglycemia on the activity or abundance of the enzymes acid phosphatase,
      cytochrome oxidase and NADPH-diaphorase in primary sensory neuron perikarya and
      the dorsal horn of the spinal cord. Quantitative densitometric characterization
      of enzyme reaction product revealed significant differences between diabetic,
      compared to control, animals for all three enzymes. Levels of acid phosphatase
      reaction product were found to be significantly reduced in both small diameter
      primary sensory somata and the dorsal horn. Cytochrome oxidase activity was found
      to be significantly lower in small primary sensory somata while NADPH-diaphorase
      labeling was found to be significantly higher in small primary sensory somata and
      significantly lower in the dorsal horn. In addition to these observed biochemical
      changes, ratiometric analysis of the number of small versus large diameter
      primary sensory perikarya in diabetic and control animals demonstrated a
      quantifiable decrease in the number of small diameter cells in the spinal ganglia
      of diabetic mice. These results suggest that the OVE26 model of diabetes mellitus
      produces an identifiable disturbance in specific metabolic pathways of select
      cells in the sensory nervous system and that this dysfunction may reflect the
      progression of a demonstrated cell loss.

PMID- 17459159
TI  - Docosahexaenoic acid and n-6 docosapentaenoic acid supplementation alter rat
      skeletal muscle fatty acid composition.
AB  - BACKGROUND: Docosahexaenoic acid (22:6n-3, DHA) and n-6 docosapentaenoic acid
      (22:5n-6, DPAn-6) are highly unsaturated fatty acids (HUFA, > or = 20 carbons, >
      or = 3 double bonds) that differ by a single carbon-carbon double bond at the
      Delta19 position. Membrane 22:6n-3 may support skeletal muscle function through
      optimal ion pump activity of sarcoplasmic reticulum and electron transport in the
      mitochondria. Typically n-3 fatty acid deficient feeding trials utilize linoleic
      acid (18:2n-6, LA) as a comparison group, possibly introducing a lower level of
      HUFA in addition to n-3 fatty acid deficiency. The use of 22:5n-6 as a dietary
      control is ideal for determining specific requirements for 22:6n-3 in various
      physiological processes. The incorporation of dietary 22:5n-6 into rat skeletal
      muscles has not been demonstrated previously. A one generation, artificial
      rearing model was utilized to supply 22:6n-3 and/or 22:5n-6 to rats from d2 after
      birth to adulthood. An n-3 fatty acid deficient, artificial milk with 18:2n-6 was
      supplemented with 22:6n-3 and/or 22:5n-6 resulting in four artificially reared
      (AR) dietary groups; AR-LA, AR-DHA, AR-DPAn-6, AR-DHA+DPAn-6. A dam reared group
      (DAM) was included as an additional control. Animals were sacrificed at 15 wks
      and soleus, white gastrocnemius and red gastrocnemius muscles were collected for
      fatty acid analyses. RESULTS: In all muscles of the DAM group, the concentration
      of 22:5n-6 was significantly lower than 22:6n-3 concentrations. While 22:5n-6 was
      elevated in the AR-LA group and the AR-DPAn-6 group, 20:4n-6 tended to be higher
      in the AR-LA muscles and not in the AR-DPAn-6 muscles. The AR-DHA+DPAn-6 had a
      slight, but non-significant increase in 22:5n-6 content. In the red gastrocnemius
      of the AR-DPAn-6 group, 22:5n-6 levels (8.1 +/- 2.8 wt. %) did not reciprocally
      replace the 22:6n-3 levels observed in AR-DHA reared rats (12.2 +/- 2.3 wt. %)
      suggesting a specific preference/requirement for 22:6n-3 in red gastrocnemius.
      CONCLUSION: Dietary 22:5n-6 is incorporated into skeletal muscles and appears to
      largely compete with 22:6n-3 for incorporation into lipids. In contrast, 18:2n-6
      feeding tends to result in elevations of 20:4n-6 and restrained increases of
      22:5n-6. As such, 22:5n-6 dietary comparison groups may be useful in elucidating
      specific requirements for 22:6n-3 to support optimal health and disease
      prevention.

PMID- 17459161
TI  - Genomic analysis of human lung fibroblasts exposed to vanadium pentoxide to
      identify candidate genes for occupational bronchitis.
AB  - BACKGROUND: Exposure to vanadium pentoxide (V2O5) is a cause of occupational
      bronchitis. We evaluated gene expression profiles in cultured human lung
      fibroblasts exposed to V2O5 in vitro in order to identify candidate genes that
      could play a role in inflammation, fibrosis, and repair during the pathogenesis
      of V2O5-induced bronchitis. METHODS: Normal human lung fibroblasts were exposed
      to V2O5 in a time course experiment. Gene expression was measured at various time
      points over a 24 hr period using the Affymetrix Human Genome U133A 2.0 Array.
      Selected genes that were significantly changed in the microarray experiment were
      validated by RT-PCR. RESULTS: V2O5 altered more than 1,400 genes, of which ~300
      were induced while >1,100 genes were suppressed. Gene ontology categories (GO)
      categories unique to induced genes included inflammatory response and immune
      response, while GO categories unique to suppressed genes included ubiquitin cycle
      and cell cycle. A dozen genes were validated by RT-PCR, including growth factors
      (HBEGF, VEGF, CTGF), chemokines (IL8, CXCL9, CXCL10), oxidative stress response
      genes (SOD2, PIPOX, OXR1), and DNA-binding proteins (GAS1, STAT1). CONCLUSION:
      Our study identified a variety of genes that could play pivotal roles in
      inflammation, fibrosis and repair during V2O5-induced bronchitis. The induction
      of genes that mediate inflammation and immune responses, as well as suppression
      of genes involved in growth arrest appear to be important to the lung fibrotic
      reaction to V2O5.

PMID- 17459162
TI  - Complementary and alternative medical therapy utilization by people with chronic
      fatiguing illnesses in the United States.
AB  - BACKGROUND: Chronic fatiguing illnesses, including chronic fatigue syndrome
      (CFS), pose a diagnostic and therapeutic challenge. Previous clinical reports
      addressed the utilization of health care provided to patients with CFS by a
      variety of practitioners with other than allopathic training, but did not examine
      the spectrum of complementary and alternative medicine (CAM) therapies used. This
      study was designed to measure CAM therapy use by persons with fatiguing illnesses
      in the United States population. METHODS: During a random-digit dialing survey to
      estimate the prevalence of CFS-like illness in urban and rural populations from
      different geographic regions of the United States, we queried the utilization of
      CAM including manipulation or body-based therapies, alternative medical systems,
      mind-body, biologically-based, and energy modalities. RESULTS: Four hundred forty
      fatigued and 444 non-fatigued persons from 2,728 households completed screening.
      Fatigued subjects included 53 persons with prolonged fatigue, 338 with chronic
      fatigue, and 49 with CFS-like illness. Mind-body therapy (primarily personal
      prayer and prayer by others) was the most frequently used CAM across all groups.
      Among women, there was a significant trend of increasing overall CAM use across
      all subgroups (p-trend = 0.003). All categories of CAM use were associated with
      significantly poorer physical health scores, and all but one (alternative
      medicine systems) were associated with significantly poorer mental health scores.
      People with CFS-like illness were significantly more likely to use body-based
      therapy (chiropractic and massage) than non-fatigued participants (OR = 2.52, CI
      = 1.32, 4.82). Use of body-based therapies increased significantly in a linear
      trend across subgroups of non-fatigued, prolonged fatigued, chronic fatigued, and
      CFS-like subjects (p-trend = 0.002). People with chronic fatigue were also
      significantly more likely to use body-based therapy (OR = 1.52, CI = 1.07, 2.16)
      and mind-body (excluding prayer) therapy than non-fatigued participants (OR =
      1.73, CI = 1.20 - 2.48). CONCLUSION: Utilization of CAM was common in fatiguing
      illnesses, and was largely accounted for by the presence of underlying conditions
      and poor physical and mental health. Compared to non-fatigued persons, those with
      CFS-like illness or chronic fatigue were most likely to use body-based and mind
      body therapies. These observations have important implications for provider
      education programs and development of intervention strategies for CFS.

PMID- 17459163
TI  - Resection of the mesopancreas (RMP): a new surgical classification of a known
      anatomical space.
AB  - BACKGROUND: Prognosis after surgical therapy for pancreatic cancer is poor and
      has been attributed to early lymph node involvement as well as to a strong
      tendency of cancer cells to infiltrate into the retropancreatic tissue and to
      spread along the peripancreatic neural plexuses. The objective of our study was
      to classify the anatomical-surgical layer of the mesopancreas and to describe the
      surgical principles relevant for resection of the mesopancreas (RMP).
      Immunohistochemical investigation of the mesopancreatic-perineural lymphogenic
      structures was carried out with the purpose of identifying possible routes of
      metastatic spread. METHODS: Resection of the mesopancreas (RMP) was performed in
      fresh corpses. Pancreas and mesopancreas were separated from each other and the
      mesopancreas was immunohistochemically investigated. RESULTS: The mesopancreas
      strains itself dorsally of the mesenteric vessels as a whitish-firm, fatty tissue
      like layer. Macroscopically, in the dissected en-bloc specimens of pancreas and
      mesopancreas nerve plexuses were found running from the dorsal site of the
      pancreatic head to the mesopancreas to establish a perineural plane.
      Immunohistochemical examinations revealed the lymphatic vessels localized in
      direct vicinity of the neuronal plexuses between pancreas and mesopancreas.
      CONCLUSION: The mesopancreas as a perineural lymphatic layer located dorsally to
      the pancreas and reaching beyond the mesenteric vessels has not been classified
      in the anatomical or surgical literature before. The aim to ensure the greatest
      possible distance from the retropancreatic lymphatic tissue which drains the
      carcinomatous focus can be achieved in patients with pancreatic cancer only by
      complete resection of the mesopancreas (RMP).

PMID- 17459164
TI  - Variance in multiplex suspension array assays: carryover of microspheres between
      sample wells.
AB  - BACKGROUND: This study was undertaken because of the accidental observation that
      a sample of 60+ beads was obtained by the instrument from a completely dry,
      unused well in a 96 well plate. Others have observed unexplained outliers in
      replicated wells. The problem was first observed on an older instrument, and
      replicated on a new instrument. METHODS AND RESULTS: Data is presented from two
      instruments using a multiple blank following well experiment that shows a
      surprising amount of carryover that has an unexpected nature. When it occurs, it
      does not necessarily decline from one well to the next. There appears to be two
      types of carryover, one that is small, predictable and declines consistently, and
      another which is potentially very large, unpredictable, and does not decline. The
      former can be compensated for or ignored. The latter cannot be addressed without
      using multiple replicated samples or an intraplex method. CONCLUSION: This
      problem has significance for analysis of results obtained with suspended
      microarray instruments. A special notation is made that biostatisticians need to
      be made aware of these results before experiments are undertaken and data
      generated for them to analyze. The problem can be handled by enough replicated
      samples, or an intraplex method. The applicability of these results to
      oligonucleotide based assays is unknown.

PMID- 17459165
TI  - Distinct phospholipase A2 enzymes regulate prostaglandin E2 and F2alpha
      production by bovine endometrial epithelial cells.
AB  - BACKGROUND: The rate-limiting step in prostaglandin (PG) biosynthesis is
      catalyzed by phospholipase A2 (PLA2) enzymes which hydrolyze arachidonic acid
      from membrane phospholipids. Despite their importance in uterine PG production,
      little is known concerning the specific PLA2 enzymes that regulate arachidonic
      acid liberation in the uterine endometrium. The objectives of this study were to
      evaluate the expression and activities of calcium-independent Group VI and Group
      IVC PLA2 (PLA2G6 and PLA2G4C) and calcium-dependent Group IVA PLA2 (PLA2G4A)
      enzymes in the regulation of bovine uterine endometrial epithelial cell PG
      production. METHODS: Bovine endometrial epithelial cells in culture were treated
      with oxytocin, interferon-tau and the PLA2G6 inhibitor bromoenol lactone, alone
      and in combination. Concentrations of PGF2alpha and PGE2 released into the medium
      were analyzed. Western blot analysis was performed on cellular protein to
      determine the effects of treatments on expression of PLA2G4A, PLA2G6 and PLA2G4C.
      Group-specific PLA2 activity assays were performed on cell lysates following
      treatment with oxytocin, interferon-tau or vehicle (control), alone and in
      combination. To further evaluate the role of specific PLA2 enzymes in uterine
      cell PG biosynthesis, cells were transfected with cDNAs encoding human PLA2G6 and
      PLA24C, treated as described above and PG assays performed. RESULTS: Constitutive
      cell production of PGF2alpha was about two-fold higher than PGE2. Oxytocin
      stimulated production of both PGs but the increase of PGF2alpha was significantly
      greater. Interferon-tau diminished oxytocin stimulation of both PGs. The PLA2G6
      inhibitor, bromoenol lactone, abolished oxytocin-stimulated production of
      PGF2alpha. Treatments had little effect on PLA2G4A protein expression. In
      contrast, oxytocin enhanced expression of PLA2G6 and this effect was diminished
      in the presence of interferon-tau. Expression of PLA2G4C was barely detectable in
      control and oxytocin treated cells but it was enhanced in cells treated with
      interferon-tau. Oxytocin stimulated PLA2 activity in assays designed to evaluate
      PLA2G6 activity and interferon-tau inhibited this response. In assays designed to
      measure PLA2G4C activity, only interferon-tau was stimulatory. Cells
      overexpressing PLA2G6 produced similar quantities of the two PGs and these values
      were significantly higher than PG production by non-transfected cells. Oxytocin
      stimulated production of both PGs and this response was inhibited by interferon
      tau. Bromoenol lactone inhibited oxtocin stimulation of PGF2alpha production but
      stimulated PGE2 production, both in the absence and presence of oxytocin. Cells
      over-expressing PLA2G4C produced more PGE2 than PGF2alpha and interferon-tau
      stimulated PGE2 production. CONCLUSION: Results from these studies indicate that
      oxytocin stimulation of uterine PGF2alpha production is mediated, at least in
      part, by up-regulation of PLA2G6 expression and activity. In addition to its
      known inhibitory effect on oxytocin receptor expression, interferon-tau represses
      oxytocin-stimulated PLA2G6 expression and activity and this contributes to
      diminished PGF2alpha production. Furthermore, endometrial cell PGE2 biosynthesis
      was associated with PLA2G4C expression and activity and interferon-tau was
      stimulatory to this process.

PMID- 17459166
TI  - Convergence and divergence in gene expression among natural populations exposed
      to pollution.
AB  - BACKGROUND: Natural populations of the teleost fish Fundulus heteroclitus
      tolerate a broad range of environmental conditions including temperature,
      salinity, hypoxia and chemical pollutants. Strikingly, populations of Fundulus
      inhabit and have adapted to highly polluted Superfund sites that are contaminated
      with persistent toxic chemicals. These natural populations provide a foundation
      to discover critical gene pathways that have evolved in a complex natural
      environment in response to environmental stressors. RESULTS: We used Fundulus
      cDNA arrays to compare metabolic gene expression patterns in the brains of
      individuals among nine populations: three independent, polluted Superfund
      populations and two genetically similar, reference populations for each Superfund
      population. We found that up to 17% of metabolic genes have evolved adaptive
      changes in gene expression in these Superfund populations. Among these genes, two
      (1.2%) show a conserved response among three polluted populations, suggesting
      common, independently evolved mechanisms for adaptation to environmental
      pollution in these natural populations. CONCLUSION: Significant differences among
      individuals between polluted and reference populations, statistical analyses
      indicating shared adaptive changes among the Superfund populations, and lack of
      reduction in gene expression variation suggest that common mechanisms of adaptive
      resistance to anthropogenic pollutants have evolved independently in multiple
      Fundulus populations. Among three independent, Superfund populations, two genes
      have a common response indicating that high selective pressures may favor
      specific responses.

PMID- 17459167
TI  - Assessing an organizational culture instrument based on the Competing Values
      Framework: exploratory and confirmatory factor analyses.
AB  - BACKGROUND: The Competing Values Framework (CVF) has been widely used in health
      services research to assess organizational culture as a predictor of quality
      improvement implementation, employee and patient satisfaction, and team
      functioning, among other outcomes. CVF instruments generally are presented as
      well-validated with reliable aggregated subscales. However, only one study in the
      health sector has been conducted for the express purpose of validation, and that
      study population was limited to hospital managers from a single geographic
      locale. METHODS: We used exploratory and confirmatory factor analyses to examine
      the underlying structure of data from a CVF instrument. We analyzed cross
      sectional data from a work environment survey conducted in the Veterans Health
      Administration (VHA). The study population comprised all staff in non-supervisory
      positions. The survey included 14 items adapted from a popular CVF instrument,
      which measures organizational culture according to four subscales: hierarchical,
      entrepreneurial, team, and rational. RESULTS: Data from 71,776 non-supervisory
      employees (approximate response rate 51%) from 168 VHA facilities were used in
      this analysis. Internal consistency of the subscales was moderate to strong
      (alpha = 0.68 to 0.85). However, the entrepreneurial, team, and rational
      subscales had higher correlations across subscales than within, indicating poor
      divergent properties. Exploratory factor analysis revealed two factors,
      comprising the ten items from the entrepreneurial, team, and rational subscales
      loading on the first factor, and two items from the hierarchical subscale loading
      on the second factor, along with one item from the rational subscale that cross
      loaded on both factors. Results from confirmatory factor analysis suggested that
      the two-subscale solution provides a more parsimonious fit to the data as
      compared to the original four-subscale model. CONCLUSION: This study suggests
      that there may be problems applying conventional CVF subscales to non
      supervisors, and underscores the importance of assessing psychometric properties
      of instruments in each new context and population to which they are applied. It
      also further highlights the challenges management scholars face in assessing
      organizational culture in a reliable and comparable way. More research is needed
      to determine if the emergent two-subscale solution is a valid or meaningful
      alternative and whether these findings generalize beyond VHA.

PMID- 17459169
TI  - Carbon stock growth in a forest stand: the power of age.
AB  - BACKGROUND: Understanding the relationship between the age of a forest stand and
      its biomass is essential for managing the forest component of the global carbon
      cycle. Since biomass increases with stand age, postponing harvesting to the age
      of biological maturity may result in the formation of a large carbon sink. This
      article quantifies the carbon sequestration capacity of forests by suggesting a
      default rule to link carbon stock and stand age. RESULTS: The age dependence of
      forest biomass is shown to be a power-law monomial where the power of age is
      theoretically estimated to be 4/5. This theoretical estimate is close to the
      known empirical estimate; therefore, it provides a scientific basis for a quick
      and transparent assessment of the benefits of postponing the harvest, suggesting
      that the annual magnitude of the sink induced by delayed harvest lies in the
      range of 1-2% of the baseline carbon stock. CONCLUSION: The results of this study
      imply that forest age could be used as an easily understood and scientifically
      sound measure of the progress in complying with national targets on the
      protection and enhancement of forest carbon sinks.

PMID- 17459168
TI  - A cricket Gene Index: a genomic resource for studying neurobiology, speciation,
      and molecular evolution.
AB  - BACKGROUND: As the developmental costs of genomic tools decline, genomic
      approaches to non-model systems are becoming more feasible. Many of these systems
      may lack advanced genetic tools but are extremely valuable models in other
      biological fields. Here we report the development of expressed sequence tags
      (EST's) in an orthopteroid insect, a model for the study of neurobiology,
      speciation, and evolution. RESULTS: We report the sequencing of 14,502 EST's from
      clones derived from a nerve cord cDNA library, and the subsequent construction of
      a Gene Index from these sequences, from the Hawaiian trigonidiine cricket Laupala
      kohalensis. The Gene Index contains 8607 unique sequences comprised of 2575
      tentative consensus (TC) sequences and 6032 singletons. For each of the unique
      sequences, an attempt was made to assign a provisional annotation and to
      categorize its function using a Gene Ontology-based classification through a
      sequence-based comparison to known proteins. In addition, a set of unique 70 base
      pair oligomers that can be used for DNA microarrays was developed. All Gene Index
      information is posted at the DFCI Gene Indices web page CONCLUSION: Orthopterans
      are models used to understand the neurophysiological basis of complex motor
      patterns such as flight and stridulation. The sequences presented in the cricket
      Gene Index will provide neurophysiologists with many genetic tools that have been
      largely absent in this field. The cricket Gene Index is one of only two gene
      indices to be developed in an evolutionary model system. Species within the genus
      Laupala have speciated recently, rapidly, and extensively. Therefore, the genes
      identified in the cricket Gene Index can be used to study the genomics of
      speciation. Furthermore, this gene index represents a significant EST resources
      for basal insects. As such, this resource is a valuable comparative tool for the
      understanding of invertebrate molecular evolution. The sequences presented here
      will provide much needed genomic resources for three distinct but overlapping
      fields of inquiry: neurobiology, speciation, and molecular evolution.

PMID- 17459170
TI  - Soluble Fas ligand inhibits angiogenesis in rheumatoid arthritis.
AB  - The characteristics of rheumatoid arthritis (RA) pathology include the
      infiltration of inflammatory leukocytes, the proliferation of synovial cells, and
      the presence of extensive angiogenesis, referred to as rheumatoid pannus. Fas
      ligand is critical to the homeostatic regulation of the immune response, but its
      role in the angiogenic process of RA remains to be defined. In this study, we
      investigated whether soluble Fas ligand (sFasL) induces synoviocyte apoptosis and
      regulates angiogenesis of endothelial cells in RA. The levels of sFasL were
      elevated in the synovial fluids of RA patients when compared to those of
      osteoarthritis (OA) patients, and they correlated inversely with vascular
      endothelial growth factor165 (VEGF165) concentrations. sFasL, ranging from 10 to
      100 ng/ml, induced the apoptosis of RA fibroblast-like synoviocytes (FLS) in
      vitro, and thereby decreased VEGF165 production. In addition, sFasL inhibited
      VEGF165-induced migration and chemotaxis of endothelial cells to basal levels in
      a manner independent of the Fas-mediated cell death. sFasL dose-dependently
      suppressed the VEGF165-stimulated increase in pAkt expression in endothelial
      cells, which might be associated with its anti-migratory effect on endothelial
      cells. Moreover, sFasL strongly inhibited neovascularization in the Matrigel plug
      in vivo. Our data suggest that sFasL shows anti-angiogenic activity within RA
      joints not only by inducing apoptosis of VEGF165-producing cells but also by
      blocking VEGF165-induced migration of endothelial cells, independent of Fas
      mediated apoptosis.

PMID- 17459172
TI  - Maternal versus child risk and the development of parent-child and family
      relationships in five high-risk populations.
AB  - Individual, dyadic, and triadic influences on the development of the family
      system were examined in the context of developmental risk. Participants were 145
      couples and their 4-month-old first-born child in six groups: controls, three
      mother-risk groups (depressed, anxious, comorbid), and two infant-risk groups
      (preterm, intrauterine growth retardation). Dyadic and triadic interactions were
      observed. Differences in parent-infant reciprocity and intrusiveness were found,
      with mother-risk groups scoring less optimally than controls and infant-risk
      groups scoring the poorest. Similar results emerged for family-level cohesion and
      rigidity. Structural modeling indicated that father involvement had an influence
      on the individual level, by reducing maternal distress, as well as on the triadic
      level, by increasing family cohesion. Maternal emotional distress affected the
      reciprocity component of early dyadic and triadic relationships, whereas infant
      negative emotionality impacted on the intrusive element of parenting and family
      level relationships. Discussion considered the multiple and pattern-specific
      influences on the family system as it is shaped by maternal and child risk
      conditions.

PMID- 17459171
TI  - Efficient inhibition of HIV-1 expression by LNA modified antisense
      oligonucleotides and DNAzymes targeted to functionally selected binding sites.
AB  - BACKGROUND: A primary concern when targeting HIV-1 RNA by means of antisense
      related technologies is the accessibility of the targets. Using a library
      selection approach to define the most accessible sites for 20-mer
      oligonucleotides annealing within the highly structured 5'-UTR of the HIV-1
      genome we have shown that there are at least four optimal targets available.
      RESULTS: The biological effect of antisense DNA and LNA oligonucleotides, DNA-
      and LNAzymes targeted to the four most accessible sites was tested for their
      abilities to block reverse transcription and dimerization of the HIV-1 RNA
      template in vitro, and to suppress HIV-1 production in cell culture. The
      neutralization of HIV-1 expression declined in the following order: antisense LNA
      > LNAzymes > DNAzymes and antisense DNA. The LNA modifications strongly enhanced
      the in vivo inhibitory activity of all the antisense constructs and some of the
      DNAzymes. Notably, two of the LNA modified antisense oligonucleotides inhibited
      HIV-1 production in cell culture very efficiently at concentration as low as 4
      nM. CONCLUSION: LNAs targeted to experimentally selected binding sites can
      function as very potent inhibitors of HIV-1 expression in cell culture and may
      potentially be developed as antiviral drug in patients.

PMID- 17459173
TI  - Understanding the transmission of attachment using variable- and relationship
      centered approaches.
AB  - The interrelations of maternal attachment representations, mother-infant
      interaction in the home, and attachment relationships were studied in 99
      adolescent mothers and their 12-month-old infants. A q-factor analysis was used
      to identify emergent profiles of mother and infant interaction. Traditional
      multivariate statistical analyses were complemented by a relationship-based
      approach utilizing latent class analysis. The results confirmed many theoretical
      predictions linking interaction with autonomous maternal representations and
      secure attachment, but failed to support a mediating role for maternal
      sensitivity. Strong associations were found between mothers displaying
      nonsensitive and disengaged interaction profiles, infants who did not interact
      harmoniously with the mother and preferred interaction with the visitor,
      unresolved maternal representations, and disorganized attachment relationships.
      Moreover, maternal nonsensitive and disengaged interaction in the home mediated
      the association between unresolved representations and disorganization. The
      results of the latent class analysis were consistent with these findings and
      revealed additional, empirically derived associations between attachment
      classifications and patterns of interactive behavior, some of which prompt a
      reconsideration of our current understanding of attachment transmission in at
      risk populations.

PMID- 17459174
TI  - Trajectories of internalizing problems across childhood: heterogeneity, external
      validity, and gender differences.
AB  - Developmental psychopathology theory speaks to the existence of early-manifesting
      internalizing problems with a heterogeneous longitudinal course. However, the
      course of internalizing problems has been investigated largely from late
      childhood onward, with methods that assume children's problem trajectories vary
      more so in rate than in qualitative functional form. This can obscure
      heterogeneity in symptom process and course, obscure onset of early gender
      differences in internalizing problems, and obscure the relevance of early
      sociocontextual risks for long-term internalizing outcomes. The present study
      addressed these issues by using person-oriented (latent growth mixture) methods
      to model heterogeneity in maternal-reported internalizing symptoms from age 2 to
      11 years (N = 1,364). Three latent trajectory classes were supported for each
      gender: two-thirds of children followed a low-stable trajectory; smaller
      proportions followed decreasing/increasing or elevated-stable trajectories.
      Although the number, shape, and predictive validity of internalizing trajectory
      classes were similar across gender, trajectory classes' initial values and rates
      of change varied significantly across gender, as did the impact of maternal
      postpartum depression and anxiety on latent growth factors. Extracted latent
      trajectories were differentially predicted by postpartum maternal
      psychopathology, and themselves, in several respects, differentially predicted
      self-reported depressive symptoms in preadolescence. However, discussion focuses
      on the need for further external validation of extracted latent classes.

PMID- 17459175
TI  - Maternal childhood abuse and offspring adjustment over time.
AB  - This study addressed the basis for the intergenerational transmission of
      psychosocial risk associated with maternal childhood abuse in relation to
      offspring adjustment. The study tested how far group differences in individual
      change in adjustment over time were explained by differences in exposure to
      specific environmental risk experiences. Data are drawn from the Avon
      Longitudinal Study of Parents and Children. Information on mothers' own
      experience of childhood abuse, offspring adjustment at ages 4 and 7 years, and
      hypothesized mediators was available for 5,619 families. A residuals scores
      analysis was used to track children's adjustment over time. Maternal childhood
      abuse was associated with poorer behavioral trajectories between ages 4 and 7
      years. Children of abused mothers were more likely to experience a range of
      negative life events between ages 4 and 7 years, including changes in family
      composition, separations from parents, "shocks and frights" and physical
      assaults. Interim life events, together with antecedent psychosocial risk
      (maternal antenatal affective symptoms, age 4 parental hostility, age 4 family
      type) fully mediated the association between maternal childhood abuse and
      offspring prognosis.The authors express their gratitude to the families who
      participated in the study. Support for these analyses was provided by a grant
      from the Medical Research Council. The Avon Longitudinal Study of Parents and
      Children (ALSPAC) is part of the World Health Organisation initiated European
      Study of Pregnancy and Childhood, and is supported, among others, by the Wellcome
      Trust, The Department of Health, The Department of the Environment, and the
      Medical Research Council. The ALSPAC study team comprises interviewers, computer
      technicians, laboratory technicians, clerical workers, research scientists,
      volunteers, and managers who continue to make the study possible.

PMID- 17459177
TI  - Identification: the missing link between joint attention and imitation?
AB  - In this paper we outline our hypothesis that human intersubjective engagement
      entails identifying with other people. We tested a prediction derived from this
      hypothesis that concerned the relation between a component of joint attention and
      a specific form of imitation. The empirical investigation involved "blind"
      ratings of videotapes from a recent study in which we tested matched children
      with and without autism for their propensity to imitate the self-/other
      orientated aspects of another person's actions. The results were in keeping with
      three a priori predictions, as follows: (a) children with autism contrasted with
      control participants in spending more time looking at the objects acted upon and
      less time looking at the tester; (b) participants with autism showed fewer
      "sharing" looks toward the tester, and although they also showed fewer "checking"
      and "orientating" looks, they were specifically less likely to show any sharing
      looks; and, critically, (c) within each group, individual differences in sharing
      looks (only) were associated with imitation of self-other orientation. We suggest
      that the propensity to adopt the bodily anchored psychological stance of another
      person is essential to certain forms of joint attention and imitation, and that a
      weak tendency to identify with others is pivotal for the developmental
      psychopathology of autism.

PMID- 17459176
TI  - Relations of effortful control, reactive undercontrol, and anger to Chinese
      children's adjustment.
AB  - The purpose of the study was to examine the zero-order and unique relations of
      effortful attentional and behavioral regulation, reactive impulsivity, and
      anger/frustration to Chinese first and second graders' internalizing and
      externalizing symptoms, as well as the prediction of adjustment from the
      interaction of anger/frustration and effortful control or impulsivity. A parent
      and teacher reported on children's anger/frustration, effortful control, and
      impulsivity. Parents reported on children's internalizing symptoms, and teachers
      and peers reported on children's externalizing symptoms. Children were classified
      as relatively high on externalizing (or comorbid), internalizing, or
      nondisordered. High impulsivity and teacher-reported anger/frustration, and low
      effortful control, were associated with externalizing problems, whereas low
      effortful control and high parent-reported anger were predictive of internalizing
      problems. Unique prediction from effortful and reactive control was obtained and
      these predictors (especially when reported by teachers) often interacted with
      anger/frustration when predicting problem behavior classification.

PMID- 17459178
TI  - Children's disruptiveness, peer rejection, friends' deviancy, and delinquent
      behaviors: a process-oriented approach.
AB  - This study examined whether peer rejection and affiliation with deviant friends
      throughout childhood could mediate the link between early disruptiveness and two
      aspects of delinquent behaviors (i.e., violence and substance use) in a sample of
      375 children. Furthermore, we tested whether the two putative mediators operated
      in a sequential manner or in a parallel manner. Participants' disruptiveness,
      peer rejection, and friends' deviancy were assessed throughout childhood (ages 7
      to 13). Delinquency-related outcomes were assessed at ages 14 and 15 years.
      Results indicate that the sequential mediational model was supported when
      delinquency-related violence was the outcome, but not when substance use was the
      outcome. The discussion stresses the differential role of peer rejection and
      affiliation with deviant friends in regard to the two outcomes considered in this
      study and in regard to the time frame when they were measured.

PMID- 17459179
TI  - Neurophysiological mechanisms of emotion regulation for subtypes of externalizing
      children.
AB  - Children referred for externalizing behavior problems may not represent a
      homogeneous population. Our objective was to assess neural mechanisms of emotion
      regulation that might distinguish subtypes of externalizing children from each
      other and from their normal age mates. Children with pure externalizing (EXT)
      problems were compared with children comorbid for externalizing and internalizing
      (MIXED) problems and with age-matched controls. Only boys were included in the
      analysis because so few girls were referred for treatment. We used a go/no-go
      task with a negative emotion induction, and we examined dense-array EEG data
      together with behavioral measures of performance. We investigated two event
      related potential (ERP) components tapping inhibitory control or self-monitoring 
      the inhibitory N2 and error-related negativity (ERN) - and we constructed source
      models estimating their cortical generators. The MIXED children's N2s increased
      in response to the emotion induction, resulting in greater amplitudes than EXT
      children in the following trial block. ERN amplitudes were greatest for control
      children and smallest for EXT children with MIXED children in between, but only
      prior to the emotion induction. These results were paralleled by behavioral
      differences in response time and performance monitoring. ERP activity was
      localized to cortical sources suggestive of the dorsal anterior cingulate for
      control children, posterior cingulate areas for the EXT children, and both
      posterior cingulate and ventral cingulate/prefrontal regions for the MIXED
      children. These findings highlight different mechanisms of self-regulation
      underlying externalizing subtypes and point toward distinct developmental
      pathways and treatment strategies.

PMID- 17459180
TI  - A comparison of selective attention and facial processing biases in typically
      developing children who are high and low in self-reported trait anxiety.
AB  - The relationship between children's anxiety and cognitive biases was examined in
      two tasks. A group of 50 children aged 10 to 11 years (mean = 11 years, SD = 3.71
      months) was given two tasks. The first tested children's selective attention (SA)
      to threat in an emotional Stroop task. The second explored facial processing
      biases using morphed angry-neutral and happy-neutral emotional expressions that
      varied in intensity. Faces with varying levels of emotion (25% emotion-75%
      neutral, 50% emotion-50% neutral, 100% emotion-0% neutral [prototype] and 150%
      emotion-0% neutral [caricature]) were judged as being angry or happy. Results
      support previous work highlighting a link between anxiety and SA to threat. In
      addition, increased anxiety in late childhood is associated with decreased
      ability to discriminate facial expression. Finally, lack of discrimination in the
      emotional expression task was related to lack of inhibition to threat in the
      Stroop task.

PMID- 17459182
TI  - Effortful control as modifier of the association between negative emotionality
      and adolescents' mental health problems.
AB  - This study examined the extent to which effortful control moderated the risk of
      internalizing or externalizing problems associated with high negative
      emotionality in a Dutch population sample of pre- and early adolescents (N =
      1,922). Internalizing and externalizing problems were assessed with the Child
      Behavior Checklist, Youth Self-Report, and Teacher Checklist of Psychopathology.
      Temperament (effortful control, fearfulness, frustration) was assessed with the
      parent version of the Revised Early Adolescent Temperament Questionnaire. The
      effects of fearfulness and frustration appeared to be attenuated by high levels
      of effortful control. The associations differed between the two domains of mental
      health investigated: effortful control reduced the effect of fearfulness on
      internalizing problems and the effect of frustration on externalizing problems.
      The effects were stronger for externalizing problems and similar for
      preadolescent (age 11) and adolescent (age 13/14) outcomes.

PMID- 17459181
TI  - Childhood adversity and youth depression: influence of gender and pubertal
      status.
AB  - This research examined three possible models to explain how childhood social
      adversity and recent stress interact to predict depression in youth: stress
      sensitization, stress amplification, and stress inoculation. Drawing from a
      stress-sensitization theory of depression, we hypothesized that exposure to
      childhood adversity, in the form of disruptions in critical interpersonal
      relationships, would lower youths' threshold for depressive reactions to recent
      interpersonal stress. We expected that this pattern of stress sensitization would
      be most salient for girls negotiating the pubertal transition. These hypotheses
      were examined in two studies: a longitudinal, questionnaire-based investigation
      of 399 youth (M = 11.66 years) and a concurrent, interview-based investigation of
      147 youth (M = 12.39 years). Findings supported the role of stress-sensitization
      processes in pubertal girls and prepubertal boys, and stress-amplification
      processes in prepubertal girls. Childhood social adversity specifically predicted
      sensitization to recent interpersonal, but not noninterpersonal, stress. These
      findings build on prior theory and research by suggesting that early adversity
      exerts context-specific effects that vary across gender and development. Future
      research will need to identify the specific mechanisms underlying this stress
      sensitization process.

PMID- 17459183
TI  - Childhood and adolescent resiliency, regulation, and executive functioning in
      relation to adolescent problems and competence in a high-risk sample.
AB  - This study first examined the respective relations of resiliency and reactive
      control with executive functioning. It then examined the relationship of these
      different domains to the development of academic and social outcomes, and to the
      emergence of internalizing and externalizing problem behavior in adolescence.
      Resiliency and reactive control were assessed from preschool to adolescence in a
      high-risk sample of boys and girls (n = 498) and then linked to component
      operations of neuropsychological executive functioning (i.e., response
      inhibition, interference control, fluency, working memory/set-shifting, planning,
      and alertness), assessed in early and late adolescence. Consistent, linear
      relations were found between resiliency and executive functions (average r =
      .17). A curvilinear relationship was observed between reactive control and
      resiliency, such that resiliency was weaker when reactive control was either very
      high or very low. In multivariate, multilevel models, executive functions
      contributed to academic competence, whereas resiliency and interference control
      jointly predicted social competence. Low resiliency, low reactive control, and
      poor response inhibition uniquely and additively predicted internalizing problem
      behavior, whereas low reactive control and poor response inhibition uniquely
      predicted externalizing problem behavior. Results are discussed in relation to
      recent trait models of regulation and the scaffolded development of competence
      and problems in childhood and adolescence.

PMID- 17459184
TI  - Developmental risks and psychosocial adjustment among low-income Brazilian youth.
AB  - Exposure to developmental risks in three domains (community, economic, and
      family), and relations between risks and psychosocial well-being, were examined
      among 918 impoverished Brazilian youth aged 14-19 (M = 15.8 years, 51.9% female)
      recruited in low-income neighborhoods in one city in Southern Brazil. High levels
      of developmental risks were reported, with levels and types of risks varying by
      gender, age, and (to a lesser extent) race. Associations between levels of risks
      in the various domains and indicators of psychological (e.g., self-esteem,
      negative emotionality) and behavioral (e.g., substance use) adjustment differed
      for male and female respondents. Findings build on prior research investigating
      the development of young people in conditions of pervasive urban poverty and
      reinforce the value of international research in this endeavor.

PMID- 17459185
TI  - Effective treatment for postpartum depression is not sufficient to improve the
      developing mother-child relationship.
AB  - Maternal depression is prevalent, and puts children at risk. Little evidence
      addresses whether treatment for maternal depression is sufficient to improve
      child outcomes. An experiment was conducted testing whether psychotherapeutic
      treatment for mothers, suffering from major depression in the postpartum period,
      would result in improved parenting and child outcomes. Participants included
      depressed women randomly assigned to interpersonal psychotherapy (n = 60) or to a
      waitlist (n = 60), and a nondepressed comparison group (n = 56). At 6 months,
      depressed mothers were less responsive to their infants, experienced more
      parenting stress, and viewed their infants more negatively than did nondepressed
      mothers. Treatment affected only parenting stress, which improved significantly
      but was still higher than that for nondepressed mothers. Eighteen months later,
      treated depressed mothers still rated their children lower in attachment
      security, higher in behavior problems, and more negative in temperament than
      nondepressed mothers. Initial response to treatment did not predict reduced risk
      for poor child outcomes. Early maternal negative perceptions of the child
      predicted negative temperament and behavior problems 18 months after treatment.
      Treatment for depression in the postpartum period should target the mother-infant
      relationship in addition to the mothers' depressive symptoms.

PMID- 17459186
TI  - Long-term effects of trauma: psychosocial functioning of the second and third
      generation of Holocaust survivors.
AB  - The long-term effects of extreme war-related trauma on the second and the third
      generation of Holocaust survivors (HS) were examined in 88 middle-class families.
      Differences in functioning between adult offspring of HS (HSO) and a comparison
      group, as well as the psychosocial functioning of adolescent grandchildren of HS,
      were studied. Degree of presence of Holocaust in the family was examined in
      families in which both parents were HSO, either mother or father was HSO, and
      neither parent was HSO. Mothers' Holocaust background was associated with higher
      levels of psychological distress and less positive parenting representations. In
      line with synergic (multiplicative) models of risk, adolescents in families where
      both parents were HSO perceived their mothers as less accepting and less
      encouraging independence, and reported less positive self-perceptions than their
      counterparts. They also perceived their fathers as less accepting and less
      encouraging independence, showed higher levels of ambivalent attachment style,
      and according to their peers, demonstrated poorer adjustment during military
      basic training than their fellow recruits from the one-parent HSO group. Parents
      and adolescents in the one-parent HSO group functioned similarly to others with
      no Holocaust background. Parenting variables mediated the association across
      generations between degree of Holocaust experience in the family of origin of the
      parents and ambivalent attachment style and self-perception of the adolescents.
      It is recommended that researchers and clinicians develop awareness of the
      possible traces of trauma in the second and the third generation despite their
      sound functioning in their daily lives.

PMID- 17459187
TI  - Use of the DeLaval cell counter (DCC) on goats' milk.
AB  - Milk quality is measured by a variety of parameters and one of these is the
      number of somatic cells in the milk. Within the bovine dairy industry there are
      maximum acceptable levels on bulk milk cell counts and these are being introduced
      into caprine dairy production. The reference method for cell counting in goats is
      the direct microscope (DM) method using pyronin Y-methyl green stain, which
      stains cell DNA. The use of the DeLaval cell counter (DCC) on goats' milk was
      compared with this reference method. Samples from 102 udder halves were cell
      counted using the direct microscope method and the DeLaval cell counter (DCC).
      Each sample was counted twice by two different observers by the DM method and
      once using DCC. DCC showed large coefficients of regression (1.03) and
      correlation (0.95) when compared with the DM cell count (F1,199=1080.0; P<0.001).
      Goat, udder half and reader type were significant factors.

PMID- 17459188
TI  - Hypocholesterolaemic effects of plant sterol analogues are independent of ABCG5
      and ABCG8 transporter expressions in hamsters.
AB  - The hypolipidaemic effects of plant sterols are well established. However,
      mechanisms by which plant sterols lower plasma cholesterol levels, particularly
      at the molecular level, have not been clearly elucidated. The objective of the
      present study was to determine whether different plant sterol analogues reduce
      plasma cholesterol levels by up regulating the sterol transporters ABCG5 and
      ABCG8 in the liver and/or small intestine. Male Golden Syrian hamsters were
      divided into eight groups. Groups 1 and 2 were fed a maize starch-casein-sucrose
      based diet that did not contain cholesterol (control; Con) or the Con diet with
      the addition of 0.25 % cholesterol (Ch-Con). Groups 3-8 were fed the Ch-Con diet
      supplemented with 1 % plant sterols, 1 % plant stanols, 1 % of a plant sterol and
      stanol mixture (50:50), 1.76 % plant sterol-fish oil esters, or 0.71 or 1.43 %
      stanol-ascorbic acid esters, respectively. After 5 weeks, the Ch-Con diet up
      regulated the ABCG5 mRNA expression and tended (P = 0.083) to increase ABCG8 mRNA
      expression in the liver, but did not affect both genes' expression in the small
      intestine compared with the Con diet. Hamsters fed 0.7 % stanol esters showed
      lower plasma cholesterol levels (P < 0.001) and also lower liver ABCG5 mRNA
      expression (P < 0.05) compared with the Ch-Con diet. Plant stanols, stanol
      esters, and sterol esters did not affect the ABCG5 or ABCG8 mRNA expressions in
      the liver and intestine although they reduced plasma cholesterol levels. These
      results suggest that plant sterols and their derivatives reduce plasma
      cholesterol levels independently from the mRNA expression of ABCG5 and ABCG8
      transporters.

PMID- 17459189
TI  - Milk as an effective post-exercise rehydration drink.
AB  - The effectiveness of low-fat milk, alone and with an additional 20 mmol/l NaCl,
      at restoring fluid balance after exercise-induced hypohydration was compared to a
      sports drink and water. After losing 1.8 (sd 0.1) % of their body mass during
      intermittent exercise in a warm environment, eleven subjects consumed a drink
      volume equivalent to 150 % of their sweat loss. Urine samples were collected
      before and for 5 h after exercise to assess fluid balance. Urine excretion over
      the recovery period did not change during the milk trials whereas there was a
      marked increase in output between 1 and 2 h after drinking water and the sports
      drink. Cumulative urine output was less after the milk drinks were consumed (611
      (sd 207) and 550 (sd 141) ml for milk and milk with added sodium, respectively,
      compared to 1184 (sd 321) and 1205 (sd 142) ml for the water and sports drink; P
      < 0.001). Subjects remained in net positive fluid balance or euhydrated
      throughout the recovery period after drinking the milk drinks but returned to net
      negative fluid balance 1 h after drinking the other drinks. The results of the
      present study suggest that milk can be an effective post-exercise rehydration
      drink and can be considered for use after exercise by everyone except those
      individuals who have lactose intolerance.

PMID- 17459190
TI  - Zinc homeostasis in 1-4 year olds consuming diets typical of US children.
AB  - Few data have evaluated Zn balance in young children after the first year of
      life. The objective of the present study was to study the relationships among Zn
      intake, absorption, endogenous faecal excretion, and retention in a group of
      healthy children. Thirty children, aged 15-48 months, were studied on a diet
      representative of their usual daily mineral intake. Zn absorption was assessed
      using a dual-tracer stable-isotope technique. Endogenous Zn faecal excretion and
      Cu absorption were determined in a subset of children. We found that Zn intake
      from the in-patient weighed dietary record (5.0 (SD 2.1) mg/d) was significantly
      greater than the current estimated average requirement (EAR; 2.5 mg/d; P 0.4, for
      all). Absolute Zn absorption was significantly related to Zn intake (r2 0.696; P
      < 0.0001), as was Zn retention (r2 0.506; P < 0.0001). Cu absorption was
      relatively high (75.1 (sd 10.8) %) despite the high Zn intake. The EAR for Zn
      based on this dataset would appear to be between 4.2 and 4.7 mg/d to allow for a
      net average retention of 120 microg/d consistent with growth needs. We concluded
      that at relatively high Zn intakes there was little evidence of down regulation
      of absorption or up regulation of urinary or endogenous faecal Zn excretion
      across the intake range studied. Zn retention was positively correlated with
      intake. A Zn intake between 4.2 and 4.7 mg/d should meet the requirement for
      normal growth for this age group.

PMID- 17459191
TI  - Effect of dietary Enterolobium cyclocarpum on microbial protein flow and nutrient
      digestibility in sheep maintained fauna-free, with total mixed fauna or with
      Entodinium caudatum monofauna.
AB  - Three groups of five wethers with ruminal and duodenal cannulas and maintained as
      either fauna-free (FF) or inoculated with total mixed fauna (TF) or Entodinium
      caudatum as a single-species monofauna (EN) were used in an experiment with two
      28 d periods. In the first period, the sheep were fed a control barley-based diet
      (40:60 concentrate to silage DM) and in the second period the diet was
      supplemented with 187 g DM of Enterolobium cyclocarpum for the last 12 d of the
      period. The diets of period 1 and 2 were isonitrogenous. There was no effect of
      fauna on apparent ruminal and total tract organic matter and fibre digestion, but
      bacterial and microbial N flow and efficiency were improved in FF sheep compared
      to TF sheep. In period 2, protozoal numbers were reduced between 31 and 88 % 2 h
      after feeding E. cyclocarpum for the third to twelfth day of supplementation and
      by an average of 25 % in samples collected over the 24 h feeding cycle.
      Supplementation of the diet with E. cyclocarpum and the consequent protozoal
      reduction in TF and EN sheep improved the flow of non-ammonia N and bacterial N
      to the small intestine and the efficiency of microbial synthesis. However, E.
      cyclocarpum reduced ruminal organic matter digestion, especially in faunated
      sheep, and total tract organic matter, N and fibre digestion. Thus, a reduction
      in the protozoal cell numbers of 25 % was sufficient to achieve the beneficial
      effects of reduced fauna on the bacterial protein supply, but diet digestibility
      was reduced.

PMID- 17459192
TI  - A high molecular weight soluble fraction of tempeh protects against fluid losses
      in Escherichia coli-infected piglet small intestine.
AB  - Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhoea in
      children and piglets. Infection of ETEC results in fluid secretion and
      electrolyte losses in the small intestine. In this study the effects of tempeh, a
      traditional fungal fermented soybean product, on fluid losses induced by ETEC
      infection in piglets was investigated. Pairs of ETEC-infected and non-infected
      small intestinal segments of piglets were perfused simultaneously for 8 h with
      pre-digested tempeh, its supernatant and saline as an internal control. In saline
      perfused segments, ETEC infection reduced net fluid absorption by more than 500
      microl/cm2, whereas this reduction was significantly less for pre-digested tempeh
      and its supernatant (75 and 282 microl/cm2, respectively). The supernatant of pre
      digested tempeh was also compared with its permeate and retentate fractions.
      These fractions were created by ultra-filtration and contained respectively low
      and high molecular weight (>5 kDa) compounds. Again ETEC infection caused a
      significant reduction of net fluid absorption when perfused with saline (386
      microl/cm2) and also with the permeate fraction (300 microl/cm2), but much less
      with the supernatant and the retentate fraction (125 and 140 microl/cm2,
      respectively). The reduction in net fluid absorption upon ETEC infection when
      perfused with supernatant of either undigested or pre-digested tempeh was not
      different. Therefore from this study it can be concluded that a high molecular
      weight soluble fraction of tempeh is able to protect against fluid losses induced
      by ETEC, suggesting that this could play a potential role in controlling ETEC
      induced diarrhoea.

PMID- 17459193
TI  - [Gene diagnosis in leukemias].

PMID- 17459194
TI  - [The new progress of the research on chromosome in leukemias].

PMID- 17459197
TI  - [The definition of fast-track surgery].

PMID- 17459196
TI  - [The key point of disease control is the improvement of management of public
      health in medical department].

PMID- 17459199
TI  - [Current perspective of techniques for fastidious microbial pathogens
      identification].

PMID- 17459200
TI  - [Screening proteins related to retinoic acid resistance by proteomic analysis].
AB  - OBJECTIVE: To compare the expression profiles of differential proteins between
      retinoic acid resistant and sensitive cells and screen the proteins related to
      retinoic acid (RA) resistance by proteomic analysis. METHODS: The total cellular
      proteins from the RA sensitive cells of the line NB4 and the RA resistant cells
      of the line MR2 obtained from a patient with acute promyelocytic leukemia (APL)
      were separated by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)
      and analyzed by PDQuest v7.1 analysis software to screen the differential protein
      spots. Differentially expressed spots were analyzed by mass spectrometry for
      peptide mass finger (PMF) data and identified by Mascot software and SWISS-PROT
      protein database. The differentially expressed proteins were verified by Western
      blotting assay and semi-quantification RT-PCR. RESULTS: 2-DE patterns of APL cell
      lines with high-resolution and reproducibility were obtained. The average spots
      of the RA resistant cell line MR2 and RA sensitive cell line NB4 were 890 +/- 45
      and 912 +/- 56 respectively. 57 significantly differentially expressed protein
      spots were screened, among which 23 protein spots were founded to be upregulated
      and 34 protein spots down regulated in the RA resistant cell line MR2. 25
      differential protein spots were identified by mass spectrometry and 17 proteins
      were successfully assigned to 13 gene-reading frames, of which one was unknown
      function protein (FLJ00279) and the others were included in the categories of
      oncoprotein (DJ-1), transcription factor (MYC promoter-binding protein 1),
      molecule chaperone (HSP70, HSP60 and protein disulfide isomerase), metabolism
      protein (prohibitin, triosephosphate isomerase 1, and calreticulin), signal
      transduction (Rho GDP dissociation inhibitor), and cytoskeleton (ACTG1 protein,
      Beta 5-tubulin, and keratin 10). The results of Western blotting were similar to
      those of 2D-PAGE and showed differential expression of DJ-1 and calreticulin in
      several isoforms. Semi-quantification RT-PCR analysis showed that there was no
      correlation between the protein expression changes and mRNA levels of HSP70 or
      HSP60. Those results indicated that post-translational events might modify or
      shear the protein content of the specific spots. CONCLUSION: The utilization of
      two-dimensional polyacrylamide gel electrophoresis coupled with mass spectrometry
      is effective in screening the all-trans RA resistance-associated proteins and
      could provide novel clue for study of elucidating all-trans RA resistance
      mechanisms.

PMID- 17459201
TI  - [Real-time PCR array for simultaneous detection of 37 kinds of fusion genes in
      leukemia].
AB  - OBJECTIVE: To develop a real-time PCR array for simultaneous quantitative
      detection of translocations/chromosomal aberrations in patients with leukemia,
      and to investigate the feasibility and utility thereof. METHODS: By construction
      and optimization a set of specific primes (totally 82 primers), an array
      containing 66 parallel PCR reactions was developed. That array was used on the
      specimens of bone marrow or peripheral blood from 31 patients with leukemia to
      detect simultaneously 37 fusion genes and 4 proto-oncogene activations often
      occurring in patients with leukemia. Eva Green fluorescent dye method was chosen
      in the protocol. Relative quantification was performed by Ct analysis and the
      result was expressed as the ratio of the target gene versus the internal control
      gene (ABL). Six patients with chronic myelocytic leukemia (CML) among the 31
      cases underwent prior to and after treatment so as to study the expression
      changes of fusion genes and/or proto-oncogene. RESULTS: The established PCR array
      showed high efficiency of amplification and good sensibility (232 copies/microl)
      in the fusion gene detected. The standard curve had a satisfying linear range
      (10(2) approximately 10(8) copies/microl), showing a good reproducibility.
      Fourteen fusion genes, including PML/RARalpha, PLZF/RARalpha, BCR/ABL, MLL/AF1,
      MLL/AF6, MLL/AF10, AML/Eto, CBFbeta/MYH11, TLS/ERG, TEL/AML1, MOZ/CBP,
      MLL/hCDCrel, LAF4/MLLT2, and FIP1L1/PDGFRalpha, and activation of all 4 proto
      oncogenes were found in the 31 samples. In one patient, 5 fusion genes and
      activation of 2 proto-oncogenes were observed. Such results were compared with
      those of RT-nested PCR in 28 samples. The comparison showed that this array was a
      bit less sensitive than RT-nested PCR, however, without significant difference
      between them (P = 0.009). The expression of BCR/ABL fusion gene, WT1 gene, and
      EVI1 gene decreased after treatment in the 6 CML patients, which was in
      accordance with the clinical features. CONCLUSION: The PCR array newly
      established successfully detects various leukemia related fusion genes and proto
      oncogene activation. It is useful in molecule diagnosis and monitoring minimal
      residual disease in leukemia, and therapeutic effect monitoring.

PMID- 17459202
TI  - [Identification of differentially expressed genes in familial acute myelogenous
      leukemia by suppression subtractive hybridization].
AB  - OBJECTIVE: To isolate genes expressed differentially from the bone marrow cells
      of patients with familial acute myelocytic leukemia and to explain the molecular
      mechanisms of the disease at the gene level. METHODS: Bone marrow cells were
      obtained from a family with cases of familial acute myelocytic leukemia for
      successive 4 generations. Super SMART cDNA synthesis and suppression subtractive
      hybridization (SSH) were performed to set up a subtractive cDNA library of
      specially or highly expressed genes. The white clones were screened and
      identified by modified differential screening technique in which the probes were
      labeled with digoxin/deoxyuridine 5'-triphosphate. Positive clones were sequenced
      and compared with the known sequences in the public databases of
      GenBank/EMBL/DDBJ using NCBI BLAST for homology analysis. The unknown fragments
      were then submitted to GenBank. RESULTS: A subtractive library of differentially
      expressed genes for the family with cases of familial acute myelocytic leukemia
      was constructed successfully. After differential screening, 28 effective
      sequences were confirmed to be positive differentially expressed gene fragments
      and were submitted to GenBank for homology analysis. Then 17 sequences were
      identified as a part of known genes, and the rests were verified as unknown
      fragments. CONCLUSION: SSH is an effective approach to isolate differentially
      expressed genes. Some genes related to cell proliferation and differentiation has
      been acquired by SSH. Eleven novel expressed sequence tags related to library
      have been successfully isolated and accepted by GenBank.

PMID- 17459203
TI  - [Proteomics analysis of bone marrow cells of acute myeloid leukemia M2a and
      prognostic significance thereof].
AB  - OBJECTIVE: To investigate the relationship between the distinct expression of
      proteins in the leukemic cells of leukemia AML-M(2)a patients before inducible
      treatment and that of the patients with relapse and the prognosis by proteomics.
      METHODS: The bone marrow mononuclear cells (BMMNC) from 17 patients with leukemia
      AML-M(2)a before inductive treatment were divided into 3 groups according to the
      duration of CCR(1): Group A (n = 11) with the CCR(1) duration exceeding 12
      months, Group B (n = 6) with the CCR(1) duration less than 6 months, and Group C,
      including the 3 cases of Group B with relapse. The proteins of the BMMNC were
      separated by two-dimensional electrophoresis, part of the differentially
      expressed proteins were identified by matrix assisted laser desorption/ionization
      time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: 6 differentially
      expressed proteins were identified between Groups A and B by MALDI-TOF-MS:
      tubulin-specific chaperone B, myeloperoxidase, the CH domain of human transgelin
      2, glutathione S-transferase, zinc finger protein, and glyceraldehyde-3-phosphate
      dehydrogenase. Three differentially-expressed proteins were identified in Group
      C: NAD (P) H dehydrogenase, hypothetical protein, and HES1. CONCLUSION: The
      expression level of distinct proteins of leukemic cells of leukemia AML-M(2)a
      patients before inductive treatments is associated with the prognosis. The
      proteins of the BMMNC of the patients would change when relapse occurs.

PMID- 17459204
TI  - [Clonality of the peripheral papilloma and cancerous cells of breast].
AB  - OBJECTIVE: To study the clonality status of peripheral papilloma (peri-MP),
      ductal carcinoma in situ (DCIS), and normal tissue of the breast using an assay
      based on inactivation mosaicism of the length-polymorphic X-chromosomes at the
      androgen receptor (AR) locus and to explore a reliable way to distinguish the
      benign and malignant (or pre-malignant) cases judged morphologically. METHODS:
      Specimens of breast tissues were obtained from 26 cases of peri-PM, 25 cases of
      peri-PM with atypical ductal hyperplasia (ADH), and 27 cases pf DCIS, 16 cases of
      developed canceration, and 20 normal women. DNA was extracted and amplified via
      nested-PCR with or without previous digestion by the methylation-sensitive
      restriction endonuclease Hha I. The products were resolved on denaturing
      polyacrylamide gels and visualized through silver staining. The clonality of
      these samples was analyzed by showing the lanes. RESULTS: Loss of polymorphism at
      the AR locus was found in all the cases with DCIS and in 10 cases (10/25, 40.0%)
      of peri-PM with ADH, indicating the monoclonality of the tumor. Twenty-four cases
      (92.3%) of the 26 cases with peri-PM and the 20 specimens of normal tissue were
      shown to be polyclonal. In the 16 cases of developed canceration identical X
      chromosome inactivation (monoclonal alterations) was observed in the cancer
      focus, parts of peri-PM with ADH, and the part of DCIS. CONCLUSION: Normal breast
      tissue and peri-PM show polyclonality and the peri-PM with ADH shows
      monoclonality. Clonality analysis may be a useful modality to screen high-risk
      cases from precancerous lesions or to distinguish between the benign hyperplasia
      and early carcinoma.

PMID- 17459205
TI  - [mRNA expression of procollagen and SMADs in lesional skin of progressive
      systemic sclerosis].
AB  - OBJECTIVE: To investigate the mRNA expression of type I and type III procollagen
      and SMADs in the lesional skin of progressive systemic sclerosis (PSS) and
      analyze the role in pathogenesis of scleroderma thereof. METHODS: Real time PCR
      was used to detect the mRNA expression of type I and type III procollagen, and
      SMADs (SMAD 2, SMAD 3, SMAD 4, and SMAD 7) in the lesional skin specimens of 11
      patients with PSS and 11 specimens of normal skin. RESULTS: Type I procollagen
      alpha1, type III procollagen alpha1, SMAD 4, and SMAD 7 were expressed at the
      mRNA level significantly higher in the lesional skin tissues of the PSS patients
      than in the normal skin tissues (all P < 0.05). SMAD 4 mRNA expression was
      positively correlated with type I procollagen alpha1 mRNA expression (r = 0.728,
      P < 0.05) and the type III procollagen alpha1 mRNA expression (r = 0.678, P <
      0.05). SMAD3 mRNA expression was positively correlated with the type I
      procollagen alpha1 mRNA expression (r = 0.859, P < 0.01). CONCLUSION: Increased
      SMAD4 mRNA in the lesional skin of systemic sclerosis is positively correlation
      with increased type I and type III procollagen alpha1 mRNA expression and may be
      one of the main pathogenesis in resulting in excessive type I and type III
      collagen accumulation in PSS lesional skin.

PMID- 17459207
TI  - [Effects of surgical treatment for low birth weight neonates with critical acute
      abdomen].
AB  - OBJECTIVE: To evaluate the effects of the surgical treatment in critical acute
      abdomen in low birth weight neonates. METHODS: The clinical data of 228 neonates
      with critical acute abdomen who underwent surgical treatment from January 2000 to
      January 2003, aged (4.1 +/- 0.7) days (1 h-7 days), 141 being preterm infants and
      87 being small for date infants, 26 with the birth weight < or = 2000 g and 202
      with the birth weight of 2000 - 2500 g, and 83 cases admitted between Jan 2000
      and Dec 2002 (first 3-year group) and 145 admitted between Jan 2003 and Jan 2006
      (last 3-year group), were analyzed retrospective Follow-up was conducted for 4
      approximately 48 months. RESULTS: Twenty-six pediatric patients died after
      operation with a hospital mortality rater of 11.4%. The mortality rates of the
      group of preterm infants, newborns with the birth body weight < or = 2000 g, and
      the first 3-year group were 14.89% (21/141), 53.84% (14/26), and 18.07% (15/83)
      respectively, all significantly higher than the full-term small for date infants,
      newborns with the birth weight of 2000 approximately 2500 g, and the last 3-year
      group [5.75% (5/87, chi(2) = 4.455, P < 0. 05), 5.94% (12/202, chi(2) = 52.324, P
      < 0. 01); and 7.59% (11/145, chi(2) = 5.745, P < 0. 05) respectively. Follow-up
      showed that all surviving infants had good gastrointestinal functions and
      approximately normal growth. CONCLUSION: Death of low birth weight neonates with
      critical acute abdomen is associated with premature birth and low birth weight.
      With the development of neonatal surgery, prenatal diagnosis, and perioperational
      therapy, the curative rate of critical acute abdomen in low birth weight neonates
      is increasing.

PMID- 17459208
TI  - [The clinical results of right ventricular outflow tract reconstruction with a
      transannular patch of autologous pericardium].
AB  - OBJECTIVE: To evaluate the application value of simultaneous enlargement of the
      pulmonary annulus and the pulmonary cusp with a transannular patch of autologous
      pericardium in right ventricular outflow tract (RVOT) reconstruction. METHODS:
      Thirty-two patients who had complex congenital heart diseases received the
      technique between Jan. 2003 and Dec. 2005. Two surgical approaches were developed
      to construct a competent neocusp with autologous pericardium that could be
      extended through the pulmonary valve annulus or valve commissures. RESULTS: There
      was only 1 early death. The postoperative complications occurred in 6 patients
      recovered uneventfully. The results of the 4 approximately 40 month follow-up in
      31 patients showed good motion of reconstructed cusps. 17 patients had no or
      trivial pulmonary insufficiency. There was mild insufficiency in 12 patients and
      moderate insufficiency in 2. None of these patients needed reoperations.
      CONCLUSION: The surgical technique of simultaneous enlargement of the pulmonary
      annulus and the pulmonary cusp with a transannular patch of autologous
      pericardium is a safe, reliable and effective way for RVOT reconstruction.
      However, further close follow-up is needed to determine the true value of this
      technique.

PMID- 17459210
TI  - [Application of 64-slice helical CT in screening of coronary artery heart disease
      among apparently healthy people: preliminary experience].
AB  - OBJECTIVE: To evaluate the value of 64-slice helical CT in screening of coronary
      artery heart disease among apparently healthy people and to explore the specific
      operation thereof. METHODS: Toshiba Aquilino 64-slice helical CT machine was used
      to scan the scope from the tracheal carina to cardio-diaphragmatic plain among
      286 apparently healthy persons aged 40 approximately 78, 188 males and 98
      females, with at least one risk factor of coronary artery heart disease, after
      the contrast Iopamidol was injected. The data thus obtained underwent after
      finishing screen are with the techniques of volume reconstruction, multiplanar
      reconstruction, curve planar reconstruction, and 3-D reconstruction so as to
      demonstrate the abnormalities of coronary artery. Twenty-eight persons with
      positive findings further underwent coronary angiography. Their results of
      coronary angiography were compared with those of the results of 64-slice helical
      CT. RESULTS: 239 of the 1523 branches of coronary artery in the 286 persons were
      diagnosed as with stenosis of different degrees, 138 being less than by 50%, 62
      being by 50% approximately 70%, and 23 being by more than 70%. Twelve of the 28
      persons who underwent angiography received coronary stent. CONCLUSION: As a
      minimally invasive examination, 64-slice helical CT is valuable in early
      detection of asymptomatic coronary heart disease.

PMID- 17459211
TI  - [3-dimension computed tomography angiography and digital subtraction angiography
      in diagnosis of intracranial aneurysm: a comparative study].
AB  - OBJECTIVE: To compare the appliance values off 3-dimension computed tomography
      (CTA) and digital subtraction angiography (DSA) in diagnosis of intracranial
      aneurysm (ICA). METHODS: Eighty-six with subarachnoid hemorrhage underwent 2-D
      DSA, and 3-DCTA and 3-D DSA, both including maximum intensity projection (MIP)
      and multiple planner reconstruction (MPR), volume rending (VR). The accuracy,
      misdiagnosis rate, and missed diagnosis rate of these 3 techniques were compared.
      No significant complication was found. RESULTS: Ninety-four aneurysms were found
      in 74 patients. CTA examination obtained satisfactory MPR, MIP, and VR images in
      all patients. There was no significant difference in accuracy between 3D-DSA and
      3D-CTA. In display of the aneurysm 3D-CTA was not significantly different from 2D
      DSA in most cases. In display of the neck of aneurysm 3D-CTA was not
      significantly different from 3D-DSA, and these 3 techniques were both superior to
      2D-DSA. CONCLUSION: 3D-CTA is the first choice examination technique for patients
      with subarachnoid hemorrhage. The information obtained by 2D-DSA, 3D-DSA, and 3D
      CTA should be considered comprehensively.

PMID- 17459212
TI  - [Expression of connective tissue growth factor in renal interstitial fibrosis
      after ureteral obstruction and effects of rapamycin thereupon: experiment with
      rats].
AB  - OBJECTIVE: Is a common feature of progressive renal diseases regardless of the
      initiating insult To clarify the role of connective tissue growth factor (CTGF)
      in after (UUO) in renal interstitial fibrosis and effects of rapamycin (RAP)
      thereupon. METHODS: Eighteen Sprague-Dawley rats were randomly divided into 3
      equal groups: unilateral ureteral obstruction (UUO) model group, undergoing
      ligation of the left ureter; RAP treatment group, undergoing ligation of the left
      ureter and intraperitoneal injection of RAP 0.04 mg.kg(-1).d(-1); and sham
      operation group. The right kidneys were taken out 7 and 14 days after the
      operation respectively to undergo renal pathological examination by Masson
      staining. Semi-quantitative RT-PCR was used to detect the mRNA expression of
      CTGF. Western blotting was performed to examine the protein expression of CTGF
      and fibronectin (FN). RESULTS: In comparison with the sham operation group, renal
      interstitial fibrosis was significant more expression in the 2 UUO groups,
      especially the UUO model group (P < 0.01). Seven and 14 days after the operation
      the levels of CTGF mRNA expression of the UUO model and RAP treatment groups
      (both P < 0.01), and the level of CTGF mRNA expression of the RAP treatment group
      was significantly lower than that of the UUO model group (P < 0.01), however,
      there was no significant difference in the level of CTGF mRNA expression between
      the 2 UUO groups 14 days after the operation. Seven and 14 days after the
      operation the levels of CTGF protein expression of the UUO model and RAP
      treatment groups were both significantly higher than that of the sham operation
      group (both P < 0.01), and the levels of CTGF protein expression of the RAP
      treatment group were significantly lower than that of the UUO model group (P <
      0.05 and P < 0.01). The levels of FN expression 7 and 14 days after the operation
      of the 2 UUO groups were both significantly higher than that of the sham
      operation group (both P < 0.01). and the level of FN expression 7 days after of
      the RAP treatment group was significantly lower than that of the UUO model group
      (P < 0.01), however, there was no significant difference in the level of FN
      expression between the 2 UUO groups 14 days after the operation. CONCLUSION: The
      expression of CTGF mRNA and that of CTGF protein increase after UUO. Rapamycin
      play a protective role in the kidney by downregulating the CTGF expression and
      alleviating the renal interstitial fibrosis following UUO.

PMID- 17459213
TI  - [Effects of controlled-release arsenic-trioxide-eluting stents on in-stent
      neointimal hyperplasia in coronary artery: experiment with dog model].
AB  - OBJECTIVE: To study the safety and efficacy of controlled-release arsenic
      trioxide (As(2)O(3))-eluting stents to reduce in-stent neointimal hyperplasia in
      coronary artery. METHODS: As(2)O(3) was sprayed onto the stainless steel coated
      with polybutyl methacrylate/nano-silica and poly-lactide-co-glycolide so as to
      make the controlled-release As(2)O(3)-eluting stents with the As(2)O(3)
      concentrations of 0, 1.6, 2.4, and 3.2 microg/mm(2). Thirty adult dogs were
      randomly divided into 5 equal groups to undergo deployment of bare stent, coated
      stent, and As(2)O(3)-eluting stent of low dose (1.6 microg/mm(2)), medium dose
      (2.4, microg/mm(2)), and high dose (3.2 microg/mm(2)) into the left anterior
      descending artery or circumflex coronary artery respectively, and aspirin 250
      mg/day was given 3 days before operation until 4 weeks after operation. Four
      weeks after the operation the dogs underwent angiography and then killed. The
      coronary artery, heart, liver, spleen, lung, kidney, and brain were taken out for
      pathological examination. RESULTS: The mean injury scores were similar in all
      groups. The values of mean neointimal thickness of the high-, medium-, and low
      dose groups were (0.14 +/- 0.05) mm, (0.15 +/- 0.04) mm, and (0.27 +/- 0.03 mm)
      respectively, all significantly lower than those of the coated stent and bare
      stent groups [(0.39 +/- 0.06) mm and (0.33 +/- 0.02) mm respectively, all P <
      0.01], with significant differences between the high and medium groups and low
      dose group (both P < 0.01). The neointimal areas of the high, medium, and low
      dose groups were (1.09 +/- 0.11) mm(2), (1.33 +/- 0.10) mm(2), and (1.93 +/-
      0.29) mm(2) respectively, all significantly smaller than those of the coated
      stent and bare stent groups [(2.44 +/- 0.15) mm(2) and (2.40 +/- 0.32) mm(2), all
      P < 0.01] with significant differences between the high and medium groups and low
      dose group (both P < 0.01). The stenosis rates of the high, medium, and low dose
      groups were (19.54 +/- 3.59)%, (22.18 +/- 3.3)%, and (36.22 +/- 5.17)%
      respectively, all significantly lower than those of the coated stent and bare
      stent groups [(50.39 +/- 3.03)%, and (46.88 +/- 5.85)% respectively, all P <
      0.01] with significant differences between the high and medium groups and low
      dose group (both P < 0.01). The luminal areas of the high, medium, and low dose
      groups were (5.14 +/- 0.55) mm(2), (4.97 +/- 0.38) mm(2), and (3.75 +/- 0.39)
      mm(2) respectively, all significantly larger than those of the coated stent and
      bare stent groups [(2.62 +/- 0.22) mm(2) and (3.10 +/- 0.66) mm(2) respectively,
      both P < 0.01] with significant differences between the high and medium groups
      and low dose group (both P < 0.01). Pathological examination did not find
      intraintimal hemorrhage, medial and adventitial necrosis, aneurysm, thrombosis,
      and inflammatory cell infiltration in all groups. CONCLUSION: Capable of
      inhibiting neointimal hyperplasia in the coronary arteries dose-dependently after
      implantation, controlled-release As(2)O(3)-eluting stents is safe and applicable
      in treating coronary diseases.

PMID- 17459214
TI  - [Construction of the enhanced green fluorescent protein eukaryotic expression
      vector carrying CagA of Helicobacter pylori].
AB  - OBJECTIVE: To construct a eukaryotic green fluorescent protein expressing vector
      containing the fragment of cytotoxin associated gene A (CagA) of Helicobacter
      pylori (Hp) so as to lay a foundation for the research of gene vaccine of gastric
      cancer. pEGFP-C3-CagA. METHODS: The fragment of gene CagA was amplified from Hp
      using PCR. The amplified product was examined by electrophoresis and sequence
      determination. This fragment was inserted into pGEM-T plasmid and pEGFP-C3
      fluorescent expression vector. The recombined plasmid pEGFP-C3-CagA was
      transfected into the gastric carcinoma cells of the strain BGC823 by lipoplasty
      method. Fluorescence microscopy was used to observe the expression of pEGFP-C3
      CagA under. RESULTS: CagA was inserted in the plasmid correctly. It was verified
      by DNA sequencing and restriction enzyme. The enhanced green fluorescent protein
      eukaryotic expression vector carrying CagA of Helicobacter pylori (pEGFP-C3-CagA)
      was recombined correctly and transfected in gastric carcinoma cell strain BGC823.
      Green fluorescence was observed in transfected gastric carcinoma cell.
      CONCLUSION: Construction of the enhanced green fluorescent protein eukaryotic
      expression vector carrying CagA was successful.

PMID- 17459217
TI  - [A meta-analysis on interleukin-1 gene cluster polymorphism and genetic
      susceptibility for ankylosing spondylitis].
AB  - OBJECTIVE: To investigate the association between interleukin (IL)-1 gene cluster
      polymorphism and the genetic susceptibility for ankylosing spondylitis (AS).
      METHODS: Relevant published data were retrieved through Pubmed, EMBASE, Cochrane
      library and Chinese Bio-medicine Database (CBM). Studies eligible for this meta
      analysis had to meet all the following inclusion criteria: (1) the content was
      associated with population-based case-control studies, (2) the study was on the
      relationship between the IL-1 gene cluster polymorphism and AS, (3) the diagnosis
      of AS was based on the modified New York criteria (1984) by the rheumatologist.
      (4) the raw data including the frequencies of alleles and certain genotypes in
      case and control groups could be collected. and (5) the distribution of studied
      loci in the populations was in accord with the Hardy-Weinberg equilibrium.
      Researches that didn't meet the inclusion criteria, as well as the duplicated
      reports, family-based studies were excluded. All analyses were conducted with the
      software 'Review Manager' Version 4.2.8. RESULTS: (1) A total of 6 literatures,
      including 9 population samples, were studied. The overall combined data were
      verified to be heterogeneous, and the heterogeneity disappeared after
      stratification by the race. Then, the fixed-effect model could be applied. (2)
      The combined data revealed the frequencies of allele 2 and its genotypes of IL
      1RN intron 2 variable number of tendem repeats were higher in the AS groups than
      in the controls in the Caucasian population (allele 2: OR=1.52, 95% CI=1.26
      approximately 1.84, P<0.01; genotype: OR=1.33, 95% CI=1.04 approximately 1.70,
      P<0.05), but lower in the AS groups than in the controls in the Mongolian
      population (allele 2: OR=0.55, 95% CI=0.38 approximately 0.81, P<0.01; genotype:
      OR=0.51, 95% CI=0.34 approximately 0.77, P<0.01). (3) The minor allele T of IL-1A
      -889C>T (rs1800587) was higher in the AS group than in the controls in the
      Caucasian population (allele T: OR=1.36, 95% CI=1.12 approximately 1.66, P<0.01;
      genotype C/T+T/T: OR=1.56, 95% CI=1.20 approximately 2.03, P<0.01). This
      distribution could not be found in the Mongolian population for this SNP. (4) The
      minor allele G of IL-1F8 SNP (rs1900287) was higher in the AS group than in the
      controls in the Caucasian population (OR=1.22, 95% CI=1.04 approximately 1.44,
      P<0.05). CONCLUSION: The genetic susceptibility for AS may be associated with the
      IL-1 gene cluster polymorphism. The relevant polymorphic sites include IL-1RN
      86bp VNTR in intron 2, IL-1A -889C>T (rs1800587) and IL-1F8 SNP (rs1900287).
      Furthermore, there is a distinct discrepancy for this association among races.

PMID- 17459218
TI  - [Neuroimaging and clinical predictors of hematoma enlargement in spontaneous
      intracerebral hemorrhage].
AB  - OBJECTIVE: To study the clinical and neuroimaging predictors of hematoma
      enlargement in spontaneous intracerebral hemorrhage (ICH). METHODS: Ninety-eight
      patients with ICH within 4 hours of onset, 60 males and 38 females, aged 56+/-16,
      underwent the first CT examination at admission and the second CT examination 24
      hours later to evaluate the occurrence of hematoma enlargement. Multivariate
      analysis was performed to assess the possible predictors. RESULTS: Twenty-six of
      the 98 ICH patients (26.5%) developed hematoma enlargement. Multivariate analysis
      revealed that the following 4 factors were independently associated with hematoma
      enlargement: interval between first CT and onset, aniso-density hematoma,
      consciousness level at admission, and the history of cerebral infarction. A
      characteristic feature indicating the hematoma enlargement- "hematoma enlargement
      border" was found and named. CONCLUSION: Hematoma enlargement after ICH has some
      clinical and neuroimaging predictors. The concepts and diagnostic criteria of
      aniso-density hematoma and hematoma enlargement border have been defined for the
      first time.

PMID- 17459219
TI  - [Primary pediatric central nervous system tumors statistic: study of 763 cases in
      a single institution].
AB  - OBJECTIVE: To investigate the epidemiology of primary pediatric central nervous
      system tumors. METHODS: The clinical data of 763 pediatric patients aged under 18
      diagnosed as with primary central nervous system tumors in the past 10 years in
      Huashan Hospital were analyzed retrospectively. RESULTS: The mean age was 12.68
      and the male to female ratio was 1.56:1. Among the tumors intracranial tumors
      accounted for 93.4% (713/763), whereas spinal tumors accounted for 6.6% (50/763).
      476 of the 763 tumors (62.4%) were supratentorial, including pineal-quadrigeminal
      tumors, which was predominant to infratentorial tumors (30.5%, 233/763). 688 of
      the 763 patients had pathological diagnosis. The most common 5 categories of
      tumors were: astrocytic tumors (25.7%, 177/688), craniopharyngioma (12.8%,
      88/688), medulloblastoma (9.3%, 64/688), germ cell tumors (8.9%, 61/688), and
      pituitary adenoma (7.5%, 52/688). CONCLUSION: As the main neurological medical
      center in the southern part of China, the statistics of Huashan Hospital can be
      representative. The epidemiology of pediatric central nervous system tumors has
      its own specialty. Therefore, it is crucial to deal with primary pediatric
      central nervous system tumors according to children's characteristics.

PMID- 17459220
TI  - [A new method to detect expiratory flow limitation in chronic obstructive
      pulmonary disease patients].
AB  - OBJECTIVE: To explore the significance of negative expiratory pressure (NEP)
      technique in detecting expiratory flow limitation (EFL) in the chronic
      obstructive pulmonary disease (COPD) patients. METHODS: NEP technique was
      performed on 54 COPD patients, 45 males and 9 females, aged 69+/-10 (Group A), 8
      COPD patients who failed to receive the routine pulmonary function tests (Group
      B), and 10 normal controls. The subjects in 3 groups, matched in age, height,
      body weight, and educational level, underwent 5-point EFL scoring, Medical
      Research Council (MRC) dyspnea scoring, 6-min walk distance scoring, and routine
      pulmonary ventilation function test. RESULTS: EFL was detected in 41 of the 54
      COPD patients in Group A. NEP test was successfully performed on the 8 patients
      of Group B, and 7 of them were found as with EFL. The level of forced expired
      volume in one second percentage (FEV1%) of the patients with the EFL scores of 2,
      3, and 4 were 55.71%+/-11.77%, 41.21%+/-13.69%, and 29.84%+/-11.65% respectively,
      all significantly lower that of the 0-score group (83.76%+/-16.44%, all P<0.05).
      Multiple stepwise regression analysis showed that only 5-point EFL score, FEV1%,
      and 6-min walking distance were associated with MRC dyspnea score, and the 5
      point EFL score showed the best associativity with dyspnea. CONCLUSION: As
      compared with FEV(1pred)%, 5-point EFL scoring is more reliable in evaluating the
      dyspnea of COPD patients, it is simple and doesn't't require any cooperation on
      the part of the patients. NEP technique can be applied in the COPD patients who
      fail to receive the routine pulmonary function tests.

PMID- 17459221
TI  - [Clinical trial with a new immunomodulatory strategy: treatment of severe sepsis
      with Ulinastatin and Maipuxin].
AB  - OBJECTIVE: To evaluate the efficacy of treatment of severe sepsis by combining
      anti-inflammatory and immune-enhancing agents. METHODS: Multiple-center,
      prospective, randomized, controlled designs. Cases were from surgical or general
      ICU of 26 university teaching hospitals. Totally, 433 adult patients developing
      severe sepsis with Marshall score 5-20 were enrolled. Patients received either
      standard treatment based on SSC direction (as group control), or additional
      Ulinastatin (urinary trypsin inhibitor) 300 K units per day+thymosin alpha1
      (Maipuxin) 1.6 mg per day for 7 days (as treatment group 1, adopted in the first
      trial), or double dosage of the above agents (as treatment group 2, adopted in
      the second trial). The outcome of 28 and 90 days, APACHEII and Marshall score,
      monocyte HLA-DR/CD14+ at several points until 28 days, and the lengths of ICU
      stay, antibiotics usage and mechanical ventilation were determinated. RESULTS: In
      the first trial (91 cases), there was no significant difference in variables
      between treatment group 1 and control at 28 days. In the second trial (342
      cases), the mortality of treatment group 2 decreased from 38.32% to 25.14%
      (P=0.0088), compared with group control at 28 days, and from 52.10% to 37.14%
      (P=0.0054) on 90 days. APACHEIIalso decreased from 14.32 to 12.70 (P=0.0384) and
      monocyte HLA-DR/CD14+ increased from 40.13% to 51.65% (P=0.0092) on 28 days in
      treatment group 2. Other variables had no significant differences between two
      groups. CONCLUSION: Treatment by the combining anti-inflammatory and immune
      enhancing agents can significantly improve the outcome of severe sepsis. The
      efficacy of this therapy seems to be dose dependent on.

PMID- 17459222
TI  - [Surgical treatment of primary thymoma].
AB  - OBJECTIVE: To summarize the clinical and pathologic features of thymoma and
      assess surgical treatment thereof. METHODS: The clinical data of 66 thymoma
      patients, 35 males and 31 females, aged 40.8 (30 approximately 59), who underwent
      surgical treatment in the past 20 years, were analyzed. By Masaoka staging
      system, underwent extensive or radical or palliative operation, most commonly
      performed through a median sternotomy and frequently requires en-bloc resection
      of one or more adjacent structures. RESULTS: Fourteen of the 66 patients had
      associated myasthenia gravis (MG). The most common symptoms included chest pain,
      MG, cough, and dyspnea; only 11 of the 66 (16.7%) patients had no symptom.
      Masaoka staging revealed stage I in 29 patients (43.9%), stage II in 16 (24.2%),
      stage III in 19 (28.8%), and stage IV in 2 (3.0%). Fourteen of the 66 patients
      underwent radical resection, resection of the whole thymus and thymoma, 40
      underwent simple resection of thymus, 5 underwent palliative resection of
      thymoma, and 6 underwent thymectomy exploration. Recurrence of tumor was observed
      in 4 patients. Postoperative radiotherapy and chemotherapy were performed 24 h
      after the operation, mainly in the cases of invasive or metastatic thymoma. One
      patient died within 30 days after the operation. CONCLUSIONS: Resection and
      postoperative radiotherapy or chemotherapy are necessary in treatment of thymoma,
      particularly complete thymectomy.

PMID- 17459223
TI  - [Application of reconstruction of lumbo-sacral internal fixation after resection
      of sacrum tuberculosis].
AB  - OBJECTIVE: To investigate the effects of resection of sacrum and TSRH-3 d
      internal fixation of the pelvis in treatment of lumbo-sacral tuberculosis.
      METHODS: twenty-eight cases with lumbo-sacral tuberculosis, including 17 cases in
      L5 approximately S1, 11 cases in L5 approximately S2, 4 cases in L5 approximately
      S3, 4 cases in S(1 approximately 3)2; underwent resection of sacrum and TSRH-3 d
      internal fixation of the pelvis, followed by corresponding chemotherapy and
      radiotherapy. Follow-up was conducted for 8 approximately 48 months. RESULTS: The
      short-term outcomes were satisfactory with reduced lumbosacral pain and
      improvement of the neurological functions to different degrees. Two cases
      experienced dysuria, I case cerebrospinal fluid leakage, 2 cases experienced
      incision infection and delayed healing, and. 1 case experienced recurrence of
      chondrosarcoma. The pain in the lumbo-sacral joint and the spinal nerve root was
      relieved obviously, No nail break, bar fracture, and loosening of screws,
      enlarged screw passage, lessened pelvic, and lowed L5 spine were found.
      CONCLUSION: Clearing of the lumbosacral tuberculotic focus and reconstruction are
      effective in achieving stabilization of the lumbar vertebrae, providing
      significant pain relief, and preserving ambulatory capacity.

PMID- 17459224
TI  - [Determination of intestinal permeability in cholelithiasis patients by oral
      administration of technetium-99m-diethylenetriaminepentaacetatic acid].
AB  - OBJECTIVE: To investigate the intestinal permeability of patients with
      cholelithiasis of different types. METHODS: Technetium-99m
      diethylenetriaminepentaacetatic acid (99mTc-DTPA) at the dose of 185 MBq (5 mCi)
      was administered orally to 56 patients of cholelithiasis, 15 cases of cholesterol
      stone (CS group) and 41 cases of pigment stone (PS group) based on the cross
      section of the stone during operation, and 17 healthy controls. A 24 h urine
      collection was obtained after the ingestion of the tracer to calculate the
      urinary excretion of DTPA. RESULTS: The mean percentage of the total ingested
      dose of 99mTc-DTPA excreted in a 24 h urinary excretion was 5.0%+/-3.6% in the CS
      group, not significantly different from that in the control group (4.5%+/-3.4%.
      F=2.18, P>0.05), and the mean percentage of the total ingested dose of 99mTc-DTPA
      excreted in a 24 h urinary excretion of the PS group was 10.5%+/-6.9%,
      significantly higher than that in the control group (F=7.62, P<0.05), showing a
      significantly increase of intestinal permeability (P<0.05). CONCLUSION: The
      intestinal permeability of the patients of pigment stone is higher than that of
      the healthy subjects. Hyperpermeability may be a factor of the pathogenesis of
      pigment stone.

PMID- 17459226
TI  - [Relationship between pulse pressure, pulse pressure index and prevalence of
      stroke among rural population in China].
AB  - OBJECTIVE: To investigate the association between pulse pressure (PP), pulse
      pressure index (PPI), and stroke in rural areas. METHODS: 29970 people>or=35
      years old in rural areas of Fuxin City, Liaoning Province, were selected by
      cluster multistage sampling. Blood pressure was measured. History of stroke was
      taken. SPSS11.5 statistical software was used for data analysis. RESULTS: (1) The
      prevalence of stroke was 2.48%. (2) The PP level of the stroke group was 65 mm
      Hg+/-19 mm Hg in men and 70 mm Hg+/-21 mm Hg in women; while the PP level of the
      non-stroke group was 52 mm Hg+/-14 mm Hg in men and 53 mm Hg+/-17 mm Hg in women.
      The PPI level of the stroke group was 0.40+/-0.08 in men and 0.42+/-0.08 in
      women; while the PPI of the non-stroke was 0.38+/-0.07 in men and 0.39+/-0.07 in
      women. The PP and PPI levels of the stroke group were significantly higher than
      those of the non-stroke group (both P<0.01). (2) The prevalence of stroke
      increased along with the increase of PP and PPI in both genders (both P<0.01).
      (3) Receiver operating characteristic (ROC) curve analysis showed that the areas
      of PP and PPI under ROC curve was 0.720 (95% CI, 0.694-0.746) and 0.581 (95% CI,
      0.553-0.610) in men when the optional cutoff was selected; and were 0.755 (95%
      CI, 0.727-0.784) and 0.681 (95% CI, 0.583-0.650) in women. The sensitivity in
      prediction of stroke of PP was higher than that of PPI; and the specificity in
      prediction of stroke of PP was lightly lower than that of PPI in men and was
      higher than that of PP in women. The area of PP under ROC curve was significantly
      larger than that of PPI (P<0.01). CONCLUSIONS: As risk factors of stroke, PP and
      PPI are associated with the prevalence of stroke. PP is superior to PPI in
      predicting the prevalence of stroke.

PMID- 17459227
TI  - [The role of estrogen in the formation and development of abdominal aortic
      aneurysm: experiment with rats].
AB  - OBJECTIVE: To investigate the role of estrogen in the formation and development
      of abdominal aortic aneurysm (AAA). METHODS: Twenty male Wistar rats were
      randomly divided into 2 equal groups: experiment group, injected with 17-beta
      estradiol (E2) intraperitoneally 1 week before the establishment of AAA once a
      day for 3 weeks (until 2 weeks after the establishment of AAA), and underwent
      infusion of pancreatic elastase into the infrarenal abdominal aorta through a
      catheter inserted into the left common iliac artery o as to establish the AAA
      model, and control group, injected with normal saline intraperitoneally for 3
      weeks. Two weeks after the establishment of AAA model, the rats underwent
      laparotomy, blood samples were collected from vena cava inferior to detect the
      level of E2 by radioimmunoassay and then the aneurysms were harvested to undergo
      immunohistochemistry and real-time PCR to detect the protein expression and mRNA
      expression of matrix metalloproteinase (MMP)-2 and MMP-9. RESULTS: The plasma E2
      level of the experiment group was (28+/-6) pg/ml, significantly higher than that
      of the control group [(5.86+/-0.24) pg/ml, P<0.01]. The aorta dilatation rate of
      the experiment group was (103+/-4)%, significantly lower than that of the control
      group [(172+/-13)%, P<0.01]. The destruction of arterial wall, degradation of
      elastic fibers, and infiltration of inflammatory cells were all more severe in
      the control group than in the experiment group. The relative mRNA expression of
      MMP-2 of the experiment group was 0.07+/-0.04, significantly lower than that of
      the control group (0.22+/-0.07, P<0.01); and the relative mRNA expression of MMP
      9 of the experiment group was 1.4+/-0.7, significantly lower than that of the
      control group (7.4+/-2.8, P<0.01). The protein expression of MMP-2 of the
      experiment group was (22+/-3)%, significantly lower than that of the control
      group [(50+/-12)%, P<0.01], and the protein expression of MMP-9 of the experiment
      group was (23+/-2)%, significantly lower than that of the control group too
      [(45+/-10)%, P<0.01]. CONCLUSIONS: Estrogen inhibits the AAA formation and
      development by reducing the MMP-2 and MMP-9 mRNA and protein expression and the
      infiltration of inflammatory cells.

PMID- 17459228
TI  - [Regulation of axon guidance cue netrin-1 on angiogenesis].
AB  - OBJECTIVE: To study the effect of netrin-1, an axon guidance cue, on
      angiogenesis. METHODS: Human umbilical cord vein endothelial cells (HUVECs) were
      isolated and cultured. Reverse transcription and polymerase chain reaction (RT
      PCR) was used to detect all the known receptors of netrin-1 in the HUVECs. Netrin
      1 and vascular endothelial growth factor (VEGF) of the concentration of 10 ng/ml
      were added into the culture fluid respectively for 72 h, cholecystokinin-8 (CCK
      8) was added, and then enzyme mark instrument was used to calculate the relative
      absorbance (A value). Other HUVECs were added into the upper chamber of the
      Transwell co-culture system and netrin-1 of different concentrations and VEGF of
      the concentration of 10 ng/ml were added into the lower chamber respectively for
      6 h, and then invert microscopy were used to observe the migration of HUVECs.
      Matrigel was added into the 96-well plate, and HUVECs and netrin-1 of different
      concentrations were added into the wells, then contrast microscopy was used to
      calculate the tube formation. Corneal micropocket assay was performed on 96
      rabbits to determine the corneal neovascularization (CNV) with treatment with
      different concentrations of netrin-1. RESULTS: Of the 6 ligands only the receptor
      UNC5B was expressed in the HUVECs. The cell counting kit-8 assay showed that the
      proliferation of HUVECs was promoted when the concentration of netrin-1 was under
      500 ng/ml, especially when the concentration was 50 ng/ml, however, when the
      netrin-1 concentrations were 1000 to 5000 ng/ml the proliferation of the HUVECs
      was inhibited (P<0.05). The migration of HUVECs was promoted when the
      concentration of netrin-1 was under 500 ng/ml, especially when the concentration
      was 100 ng/ml, however, when the netrin-1 concentrations were 1000 to 5000 ng/ml
      the migration of the HUVECs was inhibited (P<0.05). Normally HUVECs formed branch
      like and tube-like structure in the culture plate, netrin-1 did not influence the
      tube formation when the concentration was under 500 ng/ml, and inhibited the tube
      formation when the concentration was 1000 approximately 5000 ng/ml (P<0.05).
      Rabbit corneal micropocket assay showed that netrin-1 of the concentration of 100
      ng/ml and VEGF of the concentration of 10 ng/ml promoted the angiogenesis,
      however, the netrin-1 of the concentration of 5000 ng/ml inhibited the
      angiogenesis. CONCLUSION: Netrin-1 shows has a dual function, both promotive or
      inhibitory effects, on angiogenesis, depending on the concentration and its
      inhibitive effect is mediated by UNC5B.

PMID- 17459229
TI  - [Nordy inhibits cell proliferation and angiogenic factor production of malignant
      human glioma cells mediated by formylpeptide receptor].
AB  - OBJECTIVE: To explore the effect of Nordy, a synthesized lipoxygenase Inhibitor,
      on the expression of formylpeptide receptor (FPR) and its functional activities
      after activation in human malignant glioma cells. METHODS: Human malignant glioma
      cells of the line U87 were cultured and divided into 3 groups: N-formyl-methionyl
      leucyl-phenylalanine (fMLF) group, added with 100 nmol/L fMLF; Nordy group, added
      with 100 micromol/L Nordy for 12 h and then added with 100 nmol/L fMLF; and
      control group. The expression of FPR I the U87 cells was detected with indirect
      immunofluorescence staining and confocal laser scanning microscopy. The effect of
      Nordy on the U87 cell proliferation induced by fMLF was assayed by MTT method. RT
      PCR was used to detect the mRNA expression of vascular endothelial growth factor
      (VEGF) and interleukin-8 (IL-8) in the U87 cells. ELISA was used to detect
      protein secretion of VEGF and IL-8 in the supernatant. RESULTS: FPR was expressed
      on the cytoplasmic membrane of U87 cells. The mean FPR absorbance of the Nordy
      group was significantly lower than that of the fMLF group. The U87 cell
      proliferation of the Nordy group was significantly inhibited in comparison with
      the other 2 groups. The mRNA expression of VEGF and mRNA expression of IL-8 in
      the U87 cells activated by fMLF were significantly higher than those of the
      control group (both P<0.05), and Nordy significantly attenuated the mRNA
      expression of VEGF and IL-8 at different time points (all P<0.05). ELISA showed
      that the VEGF and IL-8 protein levels in the supernatant were 4.14 ng/ml+/-0.28
      ng/ml and 4.03 ng/ml+/-0.59 ng/ml respectively, and increased to 6.46 ng/ml+/
      0.33 ng/ml and 7.54 ng/ml+/-0.73 ng/ml respectively after stimulation of fMLF,
      however, the VEGF and IL-8 protein levels in the supernatant of the Nordy group
      were 3.59 ng/ml+/-0.33 ng/ml and 3.13 ng/ml+/-0.48 ng/ml respectively.
      CONCLUSION: Nordy inhibits the FPR expression and the effects in promoting the
      cell proliferation and mRNA expression and protein secretion of VEGF and IL-8
      after the activation of FPR in malignant human glioma cells, showing that Nordy
      has the effects of inhibition of tumor growth and angiogenesis.

PMID- 17459230
TI  - [Effect of extract of Ginkgo biloba leaves on expression of inducible nitric
      oxide synthase after sciatic nerve injury: experiment with rats].
AB  - OBJECTIVE: To investigate the effect of extract of Ginkgo biloba leaves (EGb50)
      on the expression of inducible nitric oxide synthase (iNOS) after sciatic nerve
      injury. METHODS: 156 male SD rats were randomly divided into 3 groups: experiment
      group (n=72), undergoing section and anastomosis of sciatic nerve and then
      gastric perfusion of EGb50 200 mg.kg-1.d-1; injury control group (n=72),
      undergoing section and anastomosis of sciatic nerve and then gastric perfusion of
      normal saline daily; and sham operation group (n=12), undergoing sham operation
      and gastric perfusion of normal saline daily. The rats were killed at different
      time points: 1, 3, 7, 14, 21, and 28 days after the operation. The sciatic nerve
      distant to the anastomotic sites with a length of 0.5 cm was cut out to undergo
      immunohistochemistry and RT-PCR to detect the protein and mRNA expression of
      iNOS. RESULTS: No obvious iNOS protein and mRNA expression was seen in the sham
      operation group. 3, 7, 14, and 21 days after operation the mean values of
      absorbance of iNOS in the sciatic nerve specimens of the experiment group were
      all significantly lower than those of the injury control group (P<0.05, P<0.01).
      High mRNA expression of iNOS began to be shown in the sciatic nerve specimens
      since 1day after the operation and remained at a high level till 7 days after and
      then began to decrease in the injury control group. The levels of mRNA expression
      of iNOS in the sciatic nerve specimens 1, 3, and 7 days after the operation of
      the experiment group were all significantly lower than those of the injury
      control group (all P<0.01), and there was no significant difference in the levels
      mRNA expression of iNOS 14, 21, and 28 days after the operation between the
      experiment group and injury control group (all>0.05). CONCLUSION: The extract of
      Gingko biloba promotes the regeneration of nervous tissues, probably by
      inhibiting the expression of iNOS.

PMID- 17459231
TI  - [Effects of different repair methods in treatment of supraspinatus tendon tear:
      experiment with rabbits].
AB  - OBJECTIVE: To compare the effects of different repair methods in treatment of
      supraspinatus tendon tear. METHODS: Forty-five New Zealand rabbits aged 4
      approximately 6 months underwent cutting off of the left supraspinatus tendon for
      the width of 8 mm, and then were randomly divided into 3 equal groups: Group A,
      undergoing suture anchor simple suture; Group B, undergoing suture anchor
      mattress suture; and Group C, undergoing transosseous mattress suture. Eight
      weeks after the operation the rabbits were killed. The shoulder girdles of 12
      rabbits randomly selected from each group were used for mechanical test to
      determine the intensity strength of the supraspinatus tendon, and the left
      shoulder girdler of the other rabbits underwent decalcification, HE staining, and
      histological study to observe the healing of the end point of the supraspinatus
      tendon. RESULTS: Two rabbits. One in Group A and on in Group B underwent
      infection. The healing rate was 93.33% for both Groups A and B, and was 100% for
      Group C, however without significant differences among them (all>0.05). The mean
      maximum tension loads of the supraspinatus tendon of Groups A, B, and C were
      82.39+/-20.70 N, 81.80+/-20.31 N, and 88.58+/-17.24 N respectively, however
      without significant differences among them (F=0.44, >0.05). Histological
      examination showed that at the end point the supraspinatus tendons of Groups A
      and B connected to the lamellar bone and that three-zone structure (tendon,
      cartilage, and bone) could be found at the end point of the supraspinatus tendon
      in Group C, but compared with the normal end point, the number of cartilage cells
      decreased. CONCLUSION: The effects of the 3 suture methods are not significantly
      different from each other for the repair of supraspinatus tendon in respect to
      healing rate and healing strength, but compared with the suture anchor simple
      suture method and suture anchor mattress suture method, the transosseous mattress
      suture method shows greater post-healing strength of tension and the tendon
      healing situation is closer to the normal tendon structure.

PMID- 17459232
TI  - [Effect of vaporized perfluorocarbon inspiration on cell apoptosis of intestine
      mucosa: experiment with pigs with acute lung injury].
AB  - OBJECTIVE: To investigate the effect of vaporized perfluorocarbon (PFC)
      inspiration on cell apoptosis of intestine mucosa. METHODS: 18 piglets are
      randomly assigned to 3 groups, VMV group (n=8), undergoing intra-bronchial
      infusion of dioctyl sodium sulfosuccinate so as to cause acute lung injury (ALI),
      then routine mechanical ventilation (MV) for 8 h during which vaporized PFC
      inspiration was given for 2 h, and then killed to have the small intestine taken
      out, CMV group (n=8), undergoing routine MV for 8 h after the establishment of
      ALI model as MV control group, and sham operation group (n=2), undergoing only
      laparotomy to take out the small intestine. Apoptosis index of intestine mucosa
      was examined by TUNEL. Immunohistochemistry was used to detect the protein
      expression of BAX and bcl-2. RT-PCR was used to detect the mRNA expression of BAX
      and bcl-2. RESULTS: The apoptotic cells were mainly distributed in the intestinal
      villi of the VMV and CMV groups, and only a few apoptotic cells could be seen in
      the sham operation group. The apoptosis rate of the VMV group was (22.9+/-2.3)%,
      significantly lower than that of the CMV group [(70.6+/-3.4)%, P<0.05]. The
      protein expression of BAX of the VMV group was significantly lower than that of
      the CMV group (P<0.05), and the protein expressing of bcl-2 of the VMV group was
      significantly higher than that of the CMV group (P<0.05). The mRNA expression of
      BAX of the VMV group was 7.10+/-0.32, significantly lower than that of the CMV
      group (9.29+/-1.06, P<0.05), and the MRNA expression of bcl-2 of the VMV group
      was 10.29+/-2.51, significantly higher than that of the CMV group (5.18+/-1.08,
      P<0.05). The mRNA expression and protein expression of BAX and bcl-2 were all at
      very low levels in the sham operating group. CONCLUSION: PFC vaporized
      inspiration may reduce mucosa apoptosis of small intestine, with the possible
      mechanism of inhibiting the expression of the BAX gene and raising the expression
      of the bcl-2 gene.

PMID- 17459233
TI  - [Expression of integrin genes in heart of septic rat].
AB  - OBJECTIVE: To investigate the expression profile of integrin genes in heart of
      septic rat and relevant mechanisms responsible for sepsis-induced heart injury.
      METHODS: Twelve 3-month-old male Wistar rats were randomized to 2 equal groups,
      sepsis model group (CLP group) undergoing ligation and perforation with needle of
      the distal caecum so as to establish sepsis model, and sham operation group (Sham
      group), undergoing sham operation only serve as controls. Twenty-four later the
      hearts of rats were rapidly excised. After determination of the hemodynamic
      parameters by using Langendorff apparatus, the isolated hearts were cut into 2
      parts vertically to undergo histopathological examination and analysis of the
      expression of integrin genes by oligonucleotide microarrays respectively.
      RESULTS: No overt pathological changes were detected in the hearts of septic
      rats, however, the cardiac output, stroke volume, heart rate, left ventricular
      developed pressure, left ventricular end-diastolic pressure, and maximum rate of
      left ventricular pressure rise of the CLP group were 29.4+/-3.3 ml/min, 0.12+/
      0.01 ml, 256+/-6 bpm, 75.6+/-4.9 mm Hg, 7.5+/-0.3 mm Hg, and 2167+/-159 mm Hg/s
      respectively, all significantly than those of the Sham group (57.8+/-2.4 ml/min,
      0.18+/-0.01 ml, 302+/-12 bpm, 90.0+/-2.7 mmHg, 8.0+/-0.3 mmHg. and 2601+/-34
      mmHg/s respectively, all P<0.01). Microarray analysis showed that 20 out of 24
      integrin genes were up-regulated by more than 2 times in the septic rat heart,
      among which the integrin alphaV and beta2 genes were upregulated and the
      expression of integrin beta1 gene was relatively insufficient. CONCLUSION:
      Maladjustment in expression of integrin genes is present in the septic rat heart.
      Up-regulation of integrin alphaV and beta2 genes may accelerate the heart injury
      mediated by inflammatory mediators, and the relatively insufficient expression of
      integrin beta1 gene may contribute to cardiac dysfunction.

PMID- 17459236
TI  - [Individual choice of new type intraocular lenses].
AB  - Novel intraocular lens enables customized cataract surgery based on individual
      needs. In order to maximize the postoperative visual outcomes, the principles on
      the selection of intraocular lens are recommended based on the affordability,
      occupation and visual habits of the patients and the pattern of practice.

PMID- 17459237
TI  - [Relationship between ciliary muscle contraction and the pseudo accommodation
      after the implantation of foldable intraocular lenses].
AB  - OBJECTIVE: To investigate the relationship between high frequency component of
      accommodative microfluctuation (HFC) and the pseudo accommodation after the
      implantation of foldable intraocular lenses (IOL). METHODS: With ARK-730A
      accommodation analyzer we checked HFC in 50 cases (50 eyes) of patients who had
      good pupil reaction to light and the pupil diameter was 2.0 approximately 3.5 mm
      approximately. Three months after the implantation of foldable IOL, the
      relationship among ciliary muscle accommodative microfluctuation, IOL movement
      and pseudo accommodation was analyzed. RESULTS: There was positive correlation
      between ciliary muscle accommodative microfluctuation and IOL movement (r =
      0.702, P < 0.01), between IOL movement and pseudo accommodation (r = 0.861, P <
      0.01), and between ciliary muscle accommodative microfluctuation and pseudo
      accommodation (r = 0.915, P < 0.01). Pseudo accommodation was greater in patients
      who showed more ciliary muscle accommodative microfluctuation and IOL movement.
      CONCLUSION: HFC induces IOL movement, and it is one of the most important reasons
      for pseudo accommodation after foldable IOL implantation.

PMID- 17459238
TI  - [The clinical efficacy of accommodative intraocular lens and multifocal
      intraocular lens in pseudophakic after phacoemulsification].
AB  - OBJECTIVE: To compare the clinical efficacy of accommodative intraocular lens and
      multifocal intraocular lens in pseudophakic after phacoemulsification. METHODS: A
      total of 54 eyes from 32 patients undergoing phacoemulsification received
      intraocular lens based on the principle of voluntary. Twenty-four eyes from 13
      patients [16 eyes from 8 male participants and 8 eyes from 5 female participants,
      mean age (60.5 +/- 6.3) years] who had implantation of 1CU accommodative
      intraocular lens were randomized into experimental group. Thirty eyes from 19
      patients [18 eyes from 11 male participants and 12 eyes from 8 female
      participants, mean age (61 +/- 6) years] who had implantation of Array multifocal
      intraocular lens were randomized into control group. All participants were age
      related cataract patients. Main outcome measures include best corrected distance
      visual acuity, distance corrected near vision, near point, the accommodation
      amplitude and stereopsis. All the clinical data were obtained at 3 months
      postoperatively and analyzed of covariance after controlling the factor of age.
      RESULTS: (1) At 3 months postoperatively, all 1CU lens maintained good
      centricity. No patients with 1CU had undergone fibrosis, conglutination and
      remarkable posterior capsule opacification (PCO). Patients who received Array
      multifocal intraocular lens had not undergone other complications. (2) At 3
      months postoperatively, best-corrected distance visual acuity were similar
      between the 1CU group and Array group (4.96 +/- 0.15 versus 5.02 +/- 0.08, P =
      0.085). (3) Distance corrected near vision were similar between the two groups
      (4.65 +/- 0.15 versus 4.60 +/- 0.10, P = 0.398). (4) Subjective near point were
      similar between the two groups [(56 +/- 9) cm versus (61 +/- 11) cm, F = 0.065, P
      = 0.80]. (5) The accommodation amplitude were similar between the two groups
      [(1.30 +/- 0.40) D versus (1.20 +/- 0.36) D, P = 0.093]. (6) Patients with a
      accommodative intraocular lens achieved significantly better stereopsis than
      patients with multifocal Intraocular lens (43.24'' +/- 18.25'' versus 60.00'' +/-
      23.09, P = 0.543). CONCLUSIONS: Patients who received 1CU accommodative
      Intraocular lens demonstrated partial near vision when kept best distance vision.
      Our research found no significant difference between two groups in corrected
      distance vision acuity, distance corrected near vision, subjective near point,
      accommodation amplitude and near vision corrected stereopsis.

PMID- 17459239
TI  - [Iris hooks and modified capsular tension ring for subluxation lens in patients
      with Marfan's syndrome].
AB  - OBJECTIVE: To evaluate clinical efficiency and safety of the iris hooks and
      modified capsular tension ring (MCTR) for the treatment of subluxation lens in
      patients with Marfan's syndrome. METHODS: This study comprised 5 patients (7
      eyes) with Marfan's syndrome and subluxation lens. After 3.2 mm clear cornea
      incision and continuous curvilinear capsulorhexis (CCC), 2 - 4 disposable nylon
      iris hooks were inserted through the stab incisions and placed in the
      capsulorhexis to support the capsule and enlarged the CCC. Following
      irrigation/aspiration, a MCTR with suture in its eyelet was placed in the capsule
      bag. After tightening and tying the suture of MCTR, the capsular bag was centered
      and fixed. A foldable AcrySof one-piece intraocular lens (IOL) was then placed in
      the capsule bag. RESULTS: Twelve months after the operation, the best corrected
      visual acuity was >/= 0.8 in six eyes and 0.7 in one eye. The scheimpflug images
      obtained from the Pentacam demonstrated that the IOL were well centered. UBM
      showed that all the MCTR and the haptics of the IOL were in the capsule bag, the
      eyelet of the MCTR was rested stably between the capsulorhexis margin and the
      iris. The retroillumination photograph indicated that only one eye had obvious
      posterior capsular opacification. No intraoperative and postoperative
      complications such as prolapse of vitreous and retina detachment was occurred.
      CONCLUSIONS: The iris hooks can provide excellent intraoperative capsule-lens
      stability and facilitate the manipulation during operation. MCTR allows
      additional suture fixation to the eye wall without damaging the capsular bag and
      maintains the long-term stability of the intraocular lens. Furthermore, MCTR is
      helpful for avoiding dislocation of the IOL due to progressive weakening of the
      zonular fibers in some patients and provides long-term safety.

PMID- 17459240
TI  - [Laser in situ keratomileusis for treatment of high hyperopic anisometropia in
      children].
AB  - OBJECTIVE: To assess the safety, efficacy, predictability and stability of the
      laser in situ keratomileusis (LASIK) procedure in high hyperopic anisometropia
      with amblyopia in pediatric patients and to study the effect of amblyopic therapy
      after the surgery. METHODS: This is a prospective and self-control study which
      included 42 children with high hyperopic anisometropic amblyopia. The age of the
      children ranged from 6 to 14 years. LASIK was performed in the eyes with higher
      degree of hyperopic under topical or general anaesthesia using the Summit's SVS
      Apex plus (L mask for simple hyperopia, 9 eyes; P mask for hyperopia and
      astigmatism, 12 eyes) and the Lumenis's Allegretto Wave (21 eyes). Postoperative
      visual acuity, refraction and the binocular vision were analyzed. Minimum follow
      up period was 6 months; 24 children had a 2-year follow-up. RESULTS: In eyes with
      +3.00 diopters (D) to +7.50 D preoperatively, the postoperative refraction in
      66.6% of eyes was within +/- 1.00 D of the expected correction. From 6 to 24
      months postoperatively, there was a mean variation from +0.67 to + 0.99 D in
      cycloplegic equivalent refraction. Best spectacle-corrected visual acuity (BSCVA)
      of distance and reading did not decrease after the surgery. The mean BSCVA of
      distance was 0.40 +/- 0.28 (P < 0.001) and reading BSCVA was 0.78 +/- 0.39 (P <
      0.001) 2 years after the surgery. Simultaneous vision, fusion, stereopsis and
      heterophoria were improved 2 years postoperatively. CONCLUSIONS: LASIK is a safe
      and effective procedure for the correction of high hyperopic anisometropia in
      children who cannot tolerate contact lens. This procedure provides a satisfactory
      predictability and refractive stability results 2 years postoperatively. The
      effects of amblyopia therapy can be improved after the surgery.

PMID- 17459241
TI  - [Preliminary clinical study of sutureless, small-incision deep lamellar
      endothelial keratoplasty surgery].
AB  - OBJECTIVE: To investigate the surgical procedure, clinical efficacy, and the
      prevention and management of complications of sutureless, small-incision deep
      lamellar endothelial keratoplasty (DLEK). METHODS: Nine patients (nine eyes) with
      bullous keratopathy underwent sutureless, small-incision DLEK surgery, six of
      them was combined with anterior vitrectomy. Visual acuity, graft clearance,
      corneal curvature, astigmatism and endothelial cell density (ECD) were observed
      over a 3 - 5 month follow-up period. RESULTS: All grafts remained transparent,
      and six eyes had improved visual acuity. After the surgery, mean corneal
      curvature was (43.96 +/- 3.38) D. Mean corneal astigmatism was (3.32 +/- 1.20)
      diopter (D). Mean ECD was (2124 +/- 278) cells/mm(2). No severe complications
      occurred. CONCLUSION: Sutureless, small-incision DLEK, as compared with
      penetrating keratoplasty (PKP) and microkeratome-associated deep lamellar
      endothelial keratoplasty, has more advantages and is expected to be the initial
      surgical treatment for bullous keratopathy.

PMID- 17459242
TI  - [Changes of type I collagen and fibronectin expressions on cultured human Tenon's
      capsule fibroblasts transfected with Smad 7 vector].
AB  - OBJECTIVE: To investigate type I collagen and fibronectin expressions in the
      cultured human Tenon's capsular fibroblasts (HTFs) transfected with Smad 7 vector
      and to elucidate the possibility of Smad 7 in blocking tissue fibrosis after
      filtration surgery. METHODS: Nucleofector(TM) was used to transfect Smad 7 vector
      into HTFs. The expressions of alpha2-type I procollagen (COL1A2) mRNA and
      fibronectin mRNA were detected by reverse transcription real-time quantitative
      polymerase chain reaction (real-time RT-PCR). The concentration of
      carboxyterminal propeptide of type I procollagen (PICP) in culture media was
      detected by radioimmunoassay. The above mentioned experiments were also detected
      before and after HTFs stimulated by TGF-beta(2) (10 ng/ml). HTFs and vector-HTFs
      were used as control groups. RESULTS: Smad 7 was successfully transfected into
      HTFs evidenced by Smad 7 over expression. The expression of COL1A2 mRNA in Smad 7
      HTFs was decreased 40.47% and 37.94%, respectively, when compared with the
      control HTFs and pCMV5-HTFs group. The PICP concentration of Smad 7-HTFs in the
      culture medium was decreased 52.10% and 57.35%, respectively, comparing to the
      two control groups. Furthermore, Smad 7-HTFs attenuated the increase of COL1A2
      mRNA expression and PICP concentration of HTFs stimulated by TGF-beta(2). There
      was no difference in the fibronectin mRNA expressions between Smad 7-HTFs and the
      two control groups. CONCLUSIONS: Smad 7 reduces the expression of COL1A2 mRNA and
      the synthesis of type I collagen, but has no effect on fibronectin mRNA
      expression, which may imply its ability to inhibit tissue fibrosis after
      filtration surgery.

PMID- 17459243
TI  - [Experimental study a new device of scleral flap stent on filtration surgery in
      normal sheep].
AB  - OBJECTIVE: To test the effectiveness and safety of a filtering drainage device, a
      scleral flap stent (SFS) made of poly methyl methacrylate (PMMA) in
      trabeculectomy (or filtering drainage-plasty) in sheep. METHODS: 32 of normal
      sheep were used. Trabeculectomy was performed in both eyes and the filtering
      drainage device, a SFS was randomly implanted under the scleral flap in one eye.
      After the surgery, the intraocular pressure (IOP) was measured by Schiotz
      tonometer; The filtering blebs and its histopathology was examined by a slit
      lamp, an ultrasound biomicroscope (UBM), and electronmicroscopy. RESULTS: The IOP
      in eyes with trabeculectomy plus SFS was statistically significant (P < 0.001)
      lower than that in eyes with trabeculectomy along at one month (11.38 +/- 1.20)
      mm Hg vs (14.05 +/- 0.93) mm Hg and at three months (11.95 +/- 1.18) mm Hg vs
      (15.2 +/- 1.09 mm Hg). Compared to the pre-operation, no difference in IOP was
      found at one month in eyes with trabeculectomy along (16.04 +/- 1.02) mm Hg vs
      (14.05 +/- 0.93) mm Hg. The filtering bleb was lasted more than 3 months in eyes
      with trabeculectomy plus SFS while existed only one month in eyes with
      trabeculectomy along by both slit lamp and UBM examination. The fibroblastic
      proliferation of filtering pathway and scar formation was found at one months
      post-operation in eyes with trabeculectomy along, however, the fibroblastic
      proliferation and the scar formation were found at three months and at six months
      after surgery in eyes with trabeculectomy plus SFS, respectively, by a light and
      electronmicroscopy examination. Tissue compliance was good and no elimination
      occurred. No toxic or adverse effects were observed in the following year post
      operatively. CONCLUSION: SFS is a safe and effective newly designed filtering
      drainage device in lowering IOP when performed together with trabeculectomy.

PMID- 17459244
TI  - [Transplantation of human limbal cells cultivated on amniotic membrane for
      reconstruction of rat corneal epithelium after alkali burn].
AB  - OBJECTIVE: To investigate the biological characters of limbal cells and evaluate
      the effect of cultivated human limbal epithelial cells transplantation on ocular
      surface reconstruction. METHODS: Human limbal cells were isolated and cultivated
      in vitro. Immunofluorescence staining and RT-PCR were used to study the phenotype
      of the cells, BrdU labeling test was used to identify the slow-cycling cells in
      the cultures. Limbal stem cell deficiency (LSCD) was established in rat cornea by
      alkali burn. Two weeks after the injury, the rats received transplantation of
      cultivated human limbal epithelial cells with amniotic membrane carrier, and then
      the therapeutic effects were evaluated by slit lamp observation, HE staining and
      immunofluorescent staining. RESULTS: On day 7, p63 and K19 were strongly
      expressed by most cells, only a few cells expressed K3. On day 14 and day 21, p63
      and K19 were still expressed by a majority of cells, while the proportion of K3
      positive cells increased, some cells co-expressed p63 and K3. RT-PCR showed that
      gene expression of both p63 and K12 were positive in cultivated limbal cells, but
      in mature superficial epithelial cells only K12 was detected. Slow-cycling cells
      were observed after cultured for 21 days with BrdU free medium. Four weeks after
      limbal stem cells combined amniotic membrane transplantation (LSAT), both slit
      lamp observation and HE staining showed that LSAT relieved the pathological
      changes of rat cornea notably as compared with the amniotic membrane
      transplantation (AMT) group and control group. The rats that received LSAT
      exhibited reconstructed corneas with the intact epithelium and improved
      transparency. Immunofluorescence staining showed that a majority of the rat
      corneal epithelial cells stained positively to anti-human nuclear antibody and K3
      antibody. CONCLUSIONS: P63 is not exclusively expressed by limbal stem cells
      (LSCs), a certain amount of p63 may also expressed by transient amplifying cells,
      LSCs are identified as p63 and K19 positive, K3/K12 negative cells. The detection
      of slow-cycling cells in the culture confirms that LSCs can be cultivated in
      vitro. Cultivated LSCs combine with amniotic membrane transplantation can
      functionally reconstruct the cornea suffered with LSCD.

PMID- 17459245
TI  - [The inhibitory effects of FK228 on retinal neovascularization].
AB  - OBJECTIVE: To explore the inhibitory effects of FK228 on retinal
      neovascularization. METHODS: One-week-old C57BL/6J mice were put into the
      environment with 75% oxygen for 5 days to establish models of vascular
      proliferation retinopathy. These mice were divided into normal control, high
      oxygen control and treatment groups (One eye of each mouse received an
      intravitreal injection of 250 ng of FK228, and the same volume of DMSO
      (dimethylsulfoxide) was injected into the other eye of the mice both in these two
      groups as a control). The ADPase histochemical straining was used for retinal
      flatmount to observe changes of retinal vessels. The inhibitory effects of FK228
      on retinal neovascularization were evaluated by counting the endotheliocyte
      nuclei of new vessels extending from retina to vitreous in the tissue-slice.
      RESULTS: Disorganized distribution and high density of retinal vessels and
      retinal neovascularization of 17-day-old mice in the high oxygen control; regular
      distributions and reduced density of retinal blood vessels in eyes in the
      treatment group were found in retinal flatmount. The number of the endotheliocyte
      nLlclei of new vessels extending from retina to vitreous was less in the eyes in
      the treatment group than which in control group (P < 0.01). CONCLUSIONS: Retinal
      neovascularization can be inhibited by intravitreal injection of FK228 which
      suggest that intravitreal injection of FK228 may have potential therapeutic
      benefits in retinal vascular disease.

PMID- 17459246
TI  - [Differentiation of rat mesenchymal stem cells in the microenvironment of
      choroidal neovascularization].
AB  - OBJECTIVE: To assay the differentiation of rat mesenchymal stem cells (MSCs) in
      the microenvironment of choroidal neovascularization (CNV). METHOD: Cultured BN
      rat MSCs were injected into the subretinal space in 25 Argon laser-induced CNV
      rat. The differentiation of MSCs was traced by immunofluorescent labeling
      successively in 5 weeks after the surgery. RESULTS: MSCs distributed on the
      surface of CNV in the 1st week after injection. From the 2nd week, CD31 positive
      MSCs were found in CNV until 5 weeks after cell injection, while rhodopsin
      positive MSCs in the photoreceptor layer were revealed until the 5th week after
      the injection. CONCLUSION: Injected MSCs in the microenvironment of CNV can
      differentiate into endothelium and photoreceptor.

PMID- 17459247
TI  - [A synthetic peptide selected by bioinformatics inhibits mouse corneal
      neovascularization].
AB  - OBJECTIVE: To identify the active anti-angiogenic region in the amino acid
      sequence of human apolipoprotein (a) [apo (a)] kringle V (KV), and to evaluate
      the role of this synthetic peptide on VEGF-induced angiogenesis of mouse cornea
      in vivo. METHODS: The characterization of the structure and biological activity
      of the amino acid sequence of apo (a) KV was analyzed using the bioinformatic
      methods which included sequence alignment, analysis of antigenicity, surface
      accessibility and hydrophilicity, and then a peptides was selected. The peptide
      was synthesized with a high efficiency solid-phase method. Corneal
      neovascularization was induced with a pellet containing 160 ng vascular
      endothelial growth factor (VEGF) in a mouse corneal micropocket model. 40 C57BL/6
      mice (40 eyes) were divided randomly into 4 groups (10 eyes per group). Four
      kinds of pellets were made containing 160 ng VEGF plus the dose range of 0.0,
      0.5, 1.0 and 1.5 microg synthetic peptide for control group, group A, group B and
      group C, respectively. Neovascularization was observed biomicroscopically on day
      7 after the operation, and the corneas were then examined histologically.
      RESULTS: The result of bioinformatic analysis showed that the peptide contained a
      majority of conservative residues and possessed fine properties of antigenicity,
      surface accessibility and hydrophilicity. The synthetic peptide at the doses of
      1.0 microg and 1.5 microg showed significant inhibition of mouse corneal
      neovascularization induced by VEGF in the parameters of vessel length, clock
      hours and area compared with the control group on day 7 after the operation (P <
      0.01). There was no difference in the two doses (1.0 microg and 1.5 microg
      peptide) in the inhibition of the neovascularization. The dose of 0.5 microg
      peptide did not show any significant inhibition of the neovascularization
      compared with the control group (P > 0.05). CONCLUSIONS: The peptide, selected
      from the amino acid sequence of apo (a) KV by bioinformatics, appears to inhibit
      VEGF-induced angiogenesis in a mouse corneal micropocket assay in vivo,
      therefore, the study suggest that this amino acid sequence may locate at the
      active anti-angiogenic region of apo (a) KV.

PMID- 17459248
TI  - [Analysis of fund sponsored articles from five ophthalmologic journals in 2005].
AB  - OBJECTIVE: To reveal the features of fund sponsored articles and the status of
      scientific research by analyzing fund sponsored articles from 5 ophthalmologic
      journals in Chinese. METHODS: Five ophthalmologic journals (Chinese Journal of
      Ophthalmology, Chinese Journal of Ocular Trauma and Occupational Eye Disease with
      Ophthalmic Surgery, Chinese Ophthalmic Research, Chinese Journal of Practical
      Ophthalmology, Chinese Journal Ocular Fundus Disease) published in Chinese in
      2005 were selected for this study. The amount, the distribution of region, the
      number of co-authors, the research direction, the number of funds obtained by
      each paper and the distribution of subjects in various research fields of fund
      sponsored articles were calculated by quantitative analysis methods. RESULTS:
      Among 1745 articles published in 2005, 222 were supported by various funds
      (12.72%). Articles sponsored by national, province/ministry and other sources
      accounted for 4.70%, 4.81% and 3.21% of all articles, respectively. The highest
      numbers of co-authors was 5.21. The top region of authors was located in
      Guangdong Province, which published 71 over 222 papers (31.98%). One hundred and
      forty nine papers (67.12%) were sponsored by single fund. The subject of fund
      sponsored articles were mainly in the field of retina (22.97%, 51/222), cornea
      (17.12%, 38/222) and lens (11.26%, 25/222). CONCLUSIONS: The quantity and the
      level of fund sponsored articles had been improved greatly in ophthalmology
      journals. However, this is still inferior to other bio-scientific journals. The
      whole academic level of ophthalmology journals should be further promoted.

PMID- 17459262
TI  - [Intraocular lens power calculations in eyes with previous corneal refractive
      surgery].
AB  - Results of intraocular lens power calculation were lower than actual required
      power in eyes with previous corneal refractive surgery because the inaccurate
      readings of corneal power obtained from standard keratometry. This causes the
      unacceptable hyperopia after cataract surgery. With increasing of population
      undergone excimer laser refractive surgery, this problem will be an obvious
      problem in years or decades. Several methods have been proposed to increase the
      accuracy of intraocular lens power calculation for cataract surgery in eyes
      undergone refractive surgery and are reviewed in this article.

PMID- 17459263
TI  - A systematic review of the effectiveness and cost-effectiveness of different
      models of community-based respite care for frail older people and their carers.
AB  - OBJECTIVES: To review the evidence for different models of community-based
      respite care for frail older people and their carers, where the participant group
      included older people with frailty, disability, cancer or dementia. Where data
      permitted, subgroups of carers and care recipients, for whom respite care is
      particularly effective or cost-effective, were to be identified. DATA SOURCES:
      Major databases were searched from 1980 to March 2005. Ongoing and recently
      completed research databases were searched in July 2005. REVIEW METHODS: Data
      from relevant studies were extracted and quality assessed. The possible effects
      of study quality on the effectiveness data and review findings were discussed.
      Where sufficient clinically and statistically similar data were available, data
      were pooled using appropriate statistical techniques. RESULTS: Twenty-two primary
      studies were included. Most of the evidence came from North America, with a
      minority of effectiveness and economic studies based in the UK. Types of service
      studied included day care, host family, in-home, institutional and video respite.
      Effectiveness evidence suggests that the consequences of respite upon carers and
      care recipients are generally small, with better controlled studies finding
      modest benefits only for certain subgroups. However, many studies report high
      levels of carer satisfaction. No reliable evidence was found that respite can
      delay entry to residential care or that respite adversely affects care
      recipients. Randomisation validity in the included randomised studies was
      sometimes unclear. Studies reported many different outcome measures, and all of
      the quasi-experimental and uncontrolled studies had methodological weaknesses.
      The descriptions of the studies did not provide sufficient detail of the methods
      of data collection or analysis, and the studies failed to describe adequately the
      groups of study participants. In some studies, only evidence to support respite
      care services was presented, rather than a balanced view of the services. Only
      five economic evaluations of respite care services were found, all of which
      compared day care with usual care and only one study was undertaken in the UK.
      Day care tended to be associated with higher costs and either similar or a slight
      increase in benefits, relative to usual care. The economic evaluations were based
      on two randomised and three quasi-experimental studies, all of which were
      included in the effectiveness analysis. The majority of studies assessed health
      and social service use and cost, but inadequate reporting limits the potential
      for exploring applicability to the UK setting. No study included generic health
      related quality of life measures, making cost-effectiveness comparisons with
      other healthcare programmes difficult. One study used sensitivity analysis to
      explore the robustness of the findings. CONCLUSIONS: The literature review
      provides some evidence that respite for carers of frail elderly people may have a
      small positive effect upon carers in terms of burden and mental or physical
      health. Carers were generally very satisfied with respite. No reliable evidence
      was found that respite either benefits or adversely affects care recipients, or
      that it delays entry to residential care. Economic evidence suggests that day
      care is at least as costly as usual care. Pilot studies are needed to inform full
      scale studies of respite in the UK.

PMID- 17459264
TI  - Assessment and therapy for voiding dysfunction after prostatectomy.

PMID- 17459265
TI  - Young man with locally advanced prostate cancer.

PMID- 17459266
TI  - Testosterone replacement therapy and prostate cancer: a word of caution.
AB  - The number of men for whom testosterone is prescribed is rapidly increasing. The
      aging man normally demonstrates a gradual decline in testosterone. Symptoms of
      hypogonadism include erectile dysfunction, diminished libido, sarcopenia,
      increased adiposity, osteopenia and osteoporosis, impaired cognition, and
      depression. There is a paucity of data regarding both efficacy and safety of
      testosterone replacement therapy. Testosterone levels have been shown to modulate
      prostate cancer risk and progression. A prospective evaluation of prostate cancer
      risk with testosterone replacement therapy has not been conducted. We outline
      concerns and recommendations for the use of testosterone replacement therapy in
      the aging man.

PMID- 17459267
TI  - Optimal cost-effective staging evaluations in prostate cancer.
AB  - A new diagnosis of prostate cancer presents to both the patient and physician
      questions regarding the best approach for further assessing the extent of disease
      prior to selecting a treatment strategy. In addition to the initial clinical data
      such as serum prostate-specific antigen level, findings on digital rectal
      examination, and core biopsy Gleason score, several procedures and imaging
      modalities are available to further stage newly diagnosed prostate cancer. A
      substantial percentage of the cost of managing prostate cancer is directly
      related to staging evaluations. Often, staging evaluations are performed that
      have limited test performance characteristics, subject the patient to unnecessary
      morbidity, or simply do not provide additional useful clinical information. It is
      important that the physician be familiar with the indications for the available
      staging modalities as well as the test performance characteristics in order to
      proceed appropriately and in an economically judicious fashion. This paper
      reviews the literature on this topic and summarizes previous experiences with
      procedures and imaging modalities for staging newly diagnosed prostate cancer.

PMID- 17459268
TI  - Management of the complications of radical prostatectomy.
AB  - Over the past several years, the morbidity associated with radical prostatectomy
      has improved due to advances in surgical technique, better understanding of male
      pelvic anatomy, and improved perioperative care. Despite these advances, patients
      are still at risk for several complications both intraoperatively and in the
      postoperative course. These risks include significant blood loss, rectal injury,
      ureteral injury, thromboembolic events, urinary incontinence, impotence, and a
      perioperative death rate of less than 1%. These risks should be reviewed and
      discussed before treating the patient with prostate cancer.

PMID- 17459269
TI  - Novel techniques for the treatment of localized prostate cancer: evidence of
      efficacy?
AB  - Radical retropubic prostatectomy and radiation therapy remain the mainstay of
      treatment for localized prostate cancer. However, with the advent of the
      Internet, more patients are arriving in physicians' offices questioning novel
      techniques for their treatment that they otherwise would not have discovered.
      This paper discusses several of these techniques, including focal cryotherapy,
      high-intensity focused ultrasound, robotic-assisted laparoscopic prostatectomy,
      diets, supplements, and hormonal therapy. We also render our opinion on their
      efficacy for treatment based on the available published studies.

PMID- 17459270
TI  - Managing the local complications of locally advanced prostate cancer.
AB  - Complications of locally advanced prostate cancer are often overlooked in the
      overall treatment of prostate cancer, can have significant morbidity, and can
      provide a challenge for the treating urologist. Despite advances in early
      detection and treatment of prostate cancer, as many as 10% of patients present
      with or develop symptomatic locally advanced prostate cancer. Prostate cancer
      locally invading the urethra can be effectively managed with transurethral
      resection or ablation procedures or urethral stenting. Obstruction of one or both
      ureters is managed with either ureteral stenting or nephrostomy drainage. Bulky
      pelvic recurrence resulting in significant hematuria, rectal involvement, or
      severe pelvic pain can be difficult to manage, with some advocating
      cystoprostatectomy or pelvic exenteration to provide palliation. Surgical
      intervention for locally advanced prostate cancer can provide significant
      improvement in quality of life and should not be restricted to patients who have
      curable disease.

PMID- 17459271
TI  - Locally ablative therapies for primary radiation failures: a review and critical
      assessment of the efficacy.
AB  - A significant number of men with prostate cancer will experience biochemical
      failure following treatment with primary radiation therapy. For patients with
      biopsy-proven recurrent cancer confined to the prostate, local salvage therapy
      may be a potentially curative treatment option. Most men, however, do not undergo
      local salvage therapy owing to difficulties in diagnosis as well as concerns over
      treatment-related complications in the salvage setting. Recently, improvements in
      technique and technology have substantially reduced the morbidity associated with
      locally ablative therapies, resulting in an increased interest in the use of
      minimally invasive therapies such as brachytherapy, cryotherapy, and high
      intensity focused ultrasound in the salvage setting. Although these treatments
      are well tolerated, concerns remain over incomplete and inadequate treatment with
      locally ablative therapies. Future studies are required to appropriately select
      candidates for salvage ablative therapies and to determine the long-term
      oncologic efficacy of these treatments.

PMID- 17459272
TI  - The basic biochemistry and molecular events of hormone therapy.
AB  - Data regarding the molecular response of prostate cancer to hormone therapy
      continue to emerge, identifying a complex network of autocrine and paracrine
      signaling events mediating the tumor response to androgen suppression. Emerging
      data provide insight into cellular pathways important in the apoptotic response
      to therapy, including the transforming growth factor-beta, insulin-like growth
      factor-1, and vascular endothelial growth factor signaling axes. They also reveal
      mechanisms of direct antitumor cytotoxicity mediated by various hormonal agents
      and highlight the importance of developing antiandrogens capable of irreversibly
      inhibiting the androgen receptor. Accumulated data emphasize the presence of
      residual androgens and persistent activation of androgen receptor signaling in
      advanced prostate tumors despite castration. These factors suggest that a
      multitargeted treatment approach designed to ablate all contributions to the
      androgen receptor signaling axis within the prostate tumor microenvironment will
      be required in order for hormonal therapy to achieve optimal antitumor efficacy.

PMID- 17459273
TI  - Bone metabolism and new targets for intervention.
AB  - Bone metastasis is a common complication of prostate cancer and is associated
      with significant morbidity for patients. Bone metabolism and prostate cancer
      metastasis to bone are complex processes. The interactions between host cells and
      metastatic prostate cancer cells are important components of organ-specific
      cancer progression. In addition to traditional treatment approaches, targeted
      therapy is currently becoming more popular. Bone metabolism, metastatic processes
      of prostate cancer, and the targeting of treatment for advanced disease are
      discussed here.

PMID- 17459274
TI  - Urologic skeletal metastases: current diagnostic and treatment strategies.
AB  - Patients with skeletal metastases from all sites are increasing in number as the
      treatment protocols for primary tumors improve survival of patients with cancer.
      While diagnosis and follow-up of the patient with urologic skeletal metastasis
      continue to become more sophisticated with new MRI techniques and the advent of
      positron emission tomography, the goal of orthopedic treatment remains the same:
      pain relief and maintenance of mobility. This paper describes the pathogenesis of
      metastasis followed by strategies currently available for accurately diagnosing,
      treating, and following the patient with skeletal metastases secondary to
      urologic malignancy.

PMID- 17459276
TI  - Does subjective tinnitus cause sexual disturbance?
AB  - OBJECTIVE: Tinnitus can cause psychological problems, which can affect sexual
      performance. The aim of this study was to investigate sexual disturbance related
      to the psychological problems of patients with subjective tinnitus. MATERIALS AND
      METHOD: The subjective tinnitus group with normal hearing levels consisted of 20
      patients (10 male, 10 female) who were nonpsychiatric. The control group
      consisted of 20 healthy patients (10 male, 10 female) with normal hearing levels
      who did not have tinnitus and were nonpsychiatric. All subjects were married and
      had an active sexual life. Using a questionnaire, the subjective tinnitus
      loudness level score (STLL-Sc) was found. Using Zung Anxiety and Depression
      Scale, self-rating depression scale (SDS) was found in the study and control
      groups. Sexual function was assessed in all male subjects with the International
      Index of Erectile Functions (IIEF) and in all female subjects with the Female
      Sexual Function Index (FSFI). RESULTS: In females, the satisfaction subscore was
      slightly lower than normal limits in both the study and control groups. In males,
      the IIEF showed an insignificant, negative correlation with the STLL-Sc and the
      SDS and a positive correlation with tinnitus duration. In females, the FSFI
      showed an insignificant negative correlation with the STLL-Sc and a positive
      correlation with tinnitus duration and the SDS. CONCLUSION: Sexual disturbance is
      seen in very quiet- and intermediate-level tinnitus sufferers in the early period
      of the disease. Over time, they become used to living with their tinnitus, and no
      loss in sexual performance is seen. In the future, we plan to investigate the
      sexual disturbance of patients with severe STLL-Scs.

PMID- 17459275
TI  - The spectrum of prostate cancer care: from curative intent to palliation.
AB  - Prostate cancer is one of the most prevalent malignancies affecting men in the
      developed world. A spectrum of disease states exists and management is tailored
      to individual patients. Increasing public awareness and prostate-specific antigen
      testing have led to earlier detection and the possibility of cure but have
      increased the risk of overtreatment of indolent disease. Advances in curative
      modalities have reduced side effects and offer patients a choice of treatments.
      Nonetheless, many need no intervention and may be safely treated with active
      monitoring. Choice and timing of therapy for locally advanced and recurrent
      disease are variable, with potential benefits of early intervention
      counterbalanced by side effects of treatment. Progress has been made in the
      management of advanced disease; skeletal-related events have been reduced and
      survival has been increased. This review examines the evidence and rationale
      behind the treatment options from curative intent to management of locally
      advanced disease and palliation of metastatic disease.

PMID- 17459277
TI  - Outcomes of the extended endoscopic approach for management of inverted
      papilloma.
AB  - BACKGROUND: Inverted papilloma (IP) is a benign tumour involving the paranasal
      sinuses. Given its tendency to recurrence and potential for malignancy, complete
      removal of the papilloma remains the treatment of choice. Since 1994, we have
      routinely employed an extended endoscopic approach for the resection of inverted
      papillomas. We present our methods and outcomes. METHOD: The study was conducted
      in an academic tertiary care hospital-based practice. It is a retrospective
      review of patients treated by a single surgeon. IP was diagnosed by biopsy before
      surgery. With computed tomography and magnetic resonance imaging, we attempt to
      identify the sites of origin and extent of IP. Cases with previous medial
      maxillectomy or invasive disease are treated via the open approach. Otherwise,
      the extended endoscopic approach is used. The tumour is debulked, and its
      attachment points are identified. Endoscopic medial maxillectomy is then
      performed. If maxillary sinus involvement in its anterior, inferior, superior, or
      lateral portion is suspected, a Caldwell-Luc approach is performed to allow for
      mucosal excision and complete removal of the anterior lateral nasal wall. When
      the lamina papyracea or ceiling of the ethmoid or sphenoid sinus is involved, the
      bony wall is resected. The frontal recess can be approached via a Lynch incision
      or an endoscopic transorbital approach. RESULTS: Twenty-two patients were
      referred for IP. Nineteen patients were treated via the extended endoscopic
      approach. The average follow-up period was 23 (3-66) months. Only 3 of 19
      patients (16%) presented with a recurrence or failure of initial surgery that
      required revision surgery. CONCLUSION: The extended endoscopic approach offers a
      safe, effective, and aesthetically acceptable treatment of most cases of IP.

PMID- 17459278
TI  - The submental island flap: a regional and free flap with a myriad of
      reconstructive applications.

PMID- 17459279
TI  - Radiation-induced soft tissue sarcomas of the head and neck.
AB  - PURPOSE: To describe the occurrence of radiation-induced soft tissue sarcomas in
      a retrospectively analyzed cohort of patients. To analyze the histologic subtypes
      and survival in this rare disease. PATIENTS AND METHODS: While performing a
      retrospective analysis of soft tissue sarcomas in patients treated between 1974
      and 1999 at the two major cancer centres in Alberta (Canada), eight patients
      presenting with nine sarcomas occurring in a previously radiated site were
      identified. Eight fulfilled the criteria for radiation-induced sarcoma. RESULTS:
      Radiation-induced sarcomas occurred between 10 months and more than 50 years
      after irradiation (median 7.35 years). Patients' ages ranged from 36 to 88 years
      (median 77.3 years) at the time of their sarcoma diagnosis. Histologically, four
      malignant fibrous histiocytomas, two dermatofibrosarcoma protuberans, two
      carcinosarcomas, and one fibrosarcoma were diagnosed. All patients received
      surgery as the primary treatment. Complete resection could not be achieved in
      three cases. Two of them died of disease. The 5-year disease-specific survival
      rate was 50%, whereas the 5-year overall survival rate was 25%. CONCLUSIONS:
      Radiotherapy can induce malignancies after a latency period of a few months to
      several years. Radiation-induced sarcomas are associated with poor overall
      prognosis. The treatment in most cases is late and ineffective. The population at
      risk for the development of radiation-induced sarcoma is increasing, so vigilance
      is required in the follow-up of those patients.

PMID- 17459280
TI  - P27 and MIB-1 expression is related to malignancy recurrence in laryngeal
      carcinoma treated with partial laryngectomy: preliminary results.
AB  - OBJECTIVE: Considerable evidence has confirmed that p27 protein plays a negative
      role in cell-cycle progression from the G1 to the S phase and is considered a
      tumour suppressor. p27 down-regulation was demonstrated in several malignancies.
      Only a few studies investigated p27's potential prognostic role in laryngeal
      squamous cell carcinoma (SCC). The aim of the present study was to determine the
      prognostic relevance of p27 expression in a cohort of laryngeal SCCs that were
      very homogeneous from a treatment viewpoint to avoid possible influences of
      treatment modalities on results; all patients underwent only partial laryngectomy
      on the primary lesion. We simultaneously investigated monoclonal antibody against
      a proliferating cell associated epitope MIB-1 expression. DESIGN AND METHODS:
      Twenty-two cases of laryngeal SCC that had undergone exclusive supracricoid or
      supraglottic laryngectomies with or without neck dissection at the Department of
      Otolaryngology of Padova University were evaluated. Primary laryngeal SCC p27
      reactivity and MIB-1 reactivity were immunohistochemically tested and evaluated
      by a workstation image analysis system. MAIN OUTCOME MEASURES: A lesion was
      considered p27 positive when more than 18.56% of the tumour cells showed diffuse
      strong staining. Samples with > 20.24% of stained cells were considered MIB-1
      positive. RESULTS: The mean p27 expression was 17% and 22% in patients with and
      without disease recurrence, respectively. Low p27 expression was statistically
      associated with disease recurrence (p = .045); on the other hand, high MIB-1
      values were associated with SCC recurrence after treatment (p = .045).
      CONCLUSIONS: The intervals of confidence analysis showed a stronger relationship
      of MIB-1 versus p27 in predicting disease recurrence in our cohort of patients
      treated only with partial laryngectomies.

PMID- 17459281
TI  - Endoscopic treatment of cis-T2 glottic cancer with a CO(2) laser: preliminary
      results from a Canadian centre.
AB  - In Canada, endoscopic resection using a CO(2) laser has been generally ignored as
      a treatment option. In this article, we present an introductory analysis of our
      clinical experience with the CO(2) laser at the QEII Health Sciences Centre in
      Halifax, Nova Scotia. Outcomes from a cohort of 36 patients with glottic cancer
      staged as Cis-T2 (7 Cis, 17 T1, 12 T2) who underwent endoscopic resection using a
      CO(2) laser between January 2002 and June 2005 were studied retrospectively. The
      mean follow-up was 16.2 months (range 0-41 months). At the time of the study, no
      patient had died of laryngeal disease, one patient had died of another disease,
      and one patient was lost to follow-up. There had been three recurrences in the
      cohort: two local recurrences and one recurrence in a regional lymph node. After
      salvage, all patients with recurrences were disease free at the time of the
      study. There were three postoperative complications in the cohort: one
      postoperative myocardial infarction, one case of respiratory distress
      postextubation, and one case of subcutaneous emphysema. The average time for the
      procedure was 0.97 hours (range 0.25-2.75 hours). The average postoperative
      length of stay was 1.2 days (range 0-12 days). Of 35 cases with follow-up, 60%
      had no reported problems with voice in their last visit and 11% reported
      consistent hoarseness or weakness. Although our oncologic results do require more
      follow-up, based on our positive experience thus far, we believe that endoscopic
      management of glottic cancer is a treatment option that may be underused in the
      Canadian health care system.

PMID- 17459282
TI  - Triangular uvulopalatal flap.
AB  - The aim of this technique is shortening and tightening the soft palate to
      increase the retropalatal upper airway patency. Postoperative scarring may also
      stabilize the soft palate and thus prevent vibration and snoring sound generation
      at this site.

PMID- 17459283
TI  - Effects of ossicular prosthesis mass and section of the stapes tendon on middle
      ear transmission.
AB  - BACKGROUND: The effects of changing prosthesis mass on middle ear transmission
      have not been previously systematically studied. Neither has the effect of stapes
      tendon sectioning. These are important parameters that can be surgically varied.
      HYPOTHESIS: Because the middle ear is compliance dominated at low frequencies,
      prosthesis mass will affect transmission of higher frequencies in the middle ear.
      METHODS: Eight fresh cadaveric temporal bones, with the incus removed, were
      loaded with a replacement prosthesis from the tympanic membrane to the stapes
      head. Laser Doppler vibrometry was used to measure stapes footplate vibrations.
      Vibrations were measured in response to chirps from 250 to 8 kHz at 90 dB SPL in
      the ear canal. The unloaded prosthesis mass was approximately 16 mg. Loadings
      with masses of approximately 2, 12, and 30 mg were placed on the stem. Recordings
      were repeated after cutting the stapes tendon. RESULTS: Mass loading affected the
      higher frequencies only, with significant effects only above 4 kHz. There was
      little low-frequency effect. Stapes tendon section showed an improvement in the
      lower frequencies but did not reach statistical significance. CONCLUSIONS: Mass
      of prostheses affects mainly higher frequencies. There is no drop in lower
      frequencies from using lower masses, so lighter-mass prostheses may be preferred.
      Stapes tendon section does not have a detrimental effect on middle ear
      transmission after ossiculoplasty.

PMID- 17459284
TI  - Effects of hearing loss on the voice in children.
AB  - The object of this paper is to report on preliminary acoustic characteristics
      obtained from a group of 10 to 12 year old males from special institution from
      Zagreb with more than mild sensorineural hearing losses. The study was structured
      as an investigation of voice and resonance characteristics of Croatian children
      with and without sensorineural hearing loss, using sustained phonation of the
      vowel /a/ which was recorded using a high-quality tape recorder carried out by
      two voice clinicians. The samples were digitized and analyzed for frequency and
      spectral characteristics by EZVoice and Bruel & Kjaer Real-time Frequency
      Analyzer and high quality sound level meter (mouth-to-microphone distance = 30
      cm). Differences were observed in perturbation measures; F0 variability; vocal
      intensity. Spectral deviations were also observed. Discussion focuses on
      application of these findings by Croatian speech and hearing specialists with the
      hearing impaired population. Results indicated the following: measures of jitter
      were significantly elevated in the hearing loss group as compared to the normal
      controls. A similar result was observed for measures of shimmer. Lack of voice
      professional's awareness of importance for making pleasant voice quality of
      hearing-impaired individuals was the initial idea of this study. Patients with
      hearing losses have been reported to show a wide variety of voice disturbances.

PMID- 17459285
TI  - Primary mucosal melanoma of the nasal cavity and paranasal sinuses: 12 years of
      experience.
AB  - INTRODUCTION: Melanomas that arise in the nasal cavity or paranasal sinuses are
      rare and have a poor prognosis. In this study, we reviewed 15 patients in a
      tertiary referral centre and analyzed their treatment results and patterns of
      treatment failure. MATERIALS AND METHODS: Fifteen patients diagnosed from January
      1994 to February 2005 at the Chang Gung Memorial Hospital were retrospectively
      reviewed. RESULTS: Eight men (53.3%) and seven (46.7%) women ranged in age from
      51 to 85 years (mean 69.0 years) at the time of diagnosis. All patients presented
      with symptoms related to the nose. The majority of patients presented with
      epistaxis (93.3%). Ten patients received surgery and postoperative radiotherapy,
      three patients received surgery and postoperative chemo- and radiotherapy, and
      one patient received radiotherapy alone. The overall actuarial survival revealed
      that 49.5% were alive at 2 years and 33.0% were alive at 5 years. The average
      time from surgery to local recurrence was 5 months, the average time from surgery
      to the occurrence of regional recurrence was 7.45 months, and the time from
      surgery to the diagnosis of distant metastasis was 10.3 months. The sites of
      distant metastasis according to frequency are the lung, liver, bone, and brain.
      The average survival after the diagnosis of distant metastasis was 8 months.
      CONCLUSION: The prognosis of mucosal melanoma of the nasal cavity is poor in our
      experience. Most of the local recurrence, regional recurrence, and distant
      metastasis occurs in the first year after surgery. For those patients in the
      first year after surgery, frequent and regular follow-up is mandatory.

PMID- 17459286
TI  - Reducing the incidence of revision rhinoplasty.
AB  - OBJECTIVES: To evaluate reasons for revision rhinoplasty in a tertiary care
      setting to help reduce the incidence of revision rhinoplasty. METHODS:
      Retrospective review of 184 consecutive revision rhinoplasty cases performed by a
      single surgeon, evaluating the major reasons for patients seeking revision
      rhinoplasty surgery. RESULTS: The senior author performed 539 rhinoplasty cases
      during the period January 2001 to June 2003. 184 were revision cases. Within this
      group 56 were the author's own revisions and 128 had undergone primary surgery by
      "other surgeons." Major revision indications were airway in 109, crookedness in
      70, residual hump in 31 and irregularity in 25 cases. Less common problems
      included inadequate reduction, tip asymmetry, tip bossae, saddle deformity and
      change of mind. The incidence of airway restriction and crookedness in the author
      group was significantly less than in the other surgeon group (p<.0001 and p =
      .0002 respectively). Other indications did not differ significantly between the
      groups. CONCLUSION: The pattern of problems requiring revision rhinoplasty is
      changing as the improved skills of the surgeon are countered by the increased
      demands of the patient. The high incidence of nasal obstruction following
      rhinoplasty reminds us that attention to the airway should not be compromised in
      the focus on cosmetic outcome. Crookedness of the nose has become a notable
      complaint by a discriminating public. All patients undergoing primary rhinoplasty
      need advice that revision rhinoplasty may be necessary either during or after the
      healing phase.

PMID- 17459287
TI  - Acetylator phenotype in Iraqi patients with atopic dermatitis.
AB  - Atopic dermatitis (AD) is a common multifactorial disease which has an itchy,
      recurrent, flexural and symmetrical eczematous eruption. There are reports that
      indicate that AD is associated with a predominantly slow acetylator status. This
      study was designed to determine the acetylator status in children with AD and
      compare it to a matched group of normal children. The study included 36 AD
      patients diagnosed clinically and 42 healthy controls. Detailed history was taken
      from the parents of each patient and disease severity was assessed using the
      Hanifin-Rajka scoring system. After overnight fast, each control subject and
      patient received a single oral dose of 50 mg of dapsone; a blood sample was
      collected after 3 hours and plasma separated for determination of dapsone and
      monoacetyldapsone by HPLC. The frequency of slow acetylators in the control group
      was 69.4 percent, and the frequency of rapid acetylators was 30.6 percent. The
      frequency of slow acetylators in AD patients was 72.2 percent and the frequency
      of rapid acetylators was 27.80 percent. There were no statistically significant
      differences between the control and AD patients groups. There was an association
      in AD patients between the acetylator status and family history of allergy as
      well as the severity assessed the Hanifin-Rajka scoring system. Although slow
      acetylators had lesions predominantly on the limbs, the distribution of lesions
      on the skin of rapid acetylators favored the face and neck. Although a slow
      acetylator status does not predispose to AD, it is associated with a different
      severity and distribution of the disease.

PMID- 17459288
TI  - Lactic acid 5 percent mouthwash is an effective mode of therapy in treatment of
      recurrent aphthous ulcerations.
AB  - BACKGROUND: Recurrent aphthous ulcerations (RAU) are the most common oral mucosal
      disease among the general population including in Iraq. There is no uniformly
      effective therapy for this disease. OBJECTIVE: To evaluate the therapeutic
      efficacy and safety of 5-percent lactic acid mouthwash in the treatment of
      patients with recurrent aphthous ulcerations. METHODS: This is a single-blind
      controlled therapeutic study. We recruited 80 subjects with early-onset oral
      aphthosis from patients who attended Baghdad Teaching Hospital Department of
      Dermatology and Venereology in the period between April 2004 and April 2005. Of
      those subjects, 10 defaulted; the remaining 70 patients were divided into two
      groups, A and B. Subjects in group A (36 patients) were instructed to use 5
      percent lactic acid mouthwash, one teaspoonful three times daily before meals.
      Subjects in group B (34 patients) were instructed to use placebo (distilled water
      mouthwash) in a similar way. Assessment of each patient of both groups was done
      by using oral clinical manifestation index (OCMI) before, after 3 days and after
      7 days of therapy. RESULTS: The mean of OCMI in group A started to decline after
      3 days of therapy and attained statistically significant lower level after 7 days
      of therapy (p <0.05). The change in the mean OCMI of group B after 3 and 7 days
      of therapy was also statistically significant (p <0.05). However, the response
      rate (percentage of change in the mean) after 3 days of therapy in group A was
      63.6 percent and in group B was 8.8 percent, and the response rate after 7 days
      of therapy in group A was 90.8 percent and in group B was 35.7 percent. The
      difference in the response rates after 3 and 7 days between groups A and B was
      statistically significant (p <0.05). No significant side effects were noticed
      apart from mild irritation in two patients using lactic acid. CONCLUSIONS: Lactic
      acid 5 percent mouthwash is a new effective mode of therapy for patients with RAU
      and had significantly reduced the signs and symptoms of the disease, especially
      when compared with placebo. The mechanism of action may be related to increasing
      spontaneous secretion of endothelial growth factor from keratinocytes.

PMID- 17459289
TI  - Evaluation of leishmanin skin test and its relationship with the clinical form
      and duration of cutaneous leishmaniasis.
AB  - BACKGROUND: Cellular immunity plays a major role in natural defense against
      cutaneous leishmaniasis. The leishmanin skin test (LST) is one method of
      evaluating the infected individual's immune response to leishmania. Our objective
      in this study was to evaluate the relationship between positivity of the LST with
      duration of disease, clinical form, number of lesions, and age and gender of the
      patient. MATERIALS AND METHODS: This open study was performed on 198 patients who
      were affected by cutaneous leishmaniasis before any treatment was administered.
      Following confirmation of the diagnosis of cutaneous leishmaniasis, relevant data
      were recorded, including age, gender, occupation, address, duration of disease,
      clinical form, location of the lesions, and the number of the lesions. After
      performing the leishmanin skin test, patients were treated for leishmaniasis
      according to the type and severity of the disease. For patients whose LST was
      initially negative, the test was repeated every 15 days. If the LST was still
      negative after 4 months, the test was repeated every 3 months; if the LST
      remained negative 12 months after the first test, the result was considered
      negative. The collected data were statistically analyzed using the SPSS program.
      RESULTS: In 179 patients (90.4%) the test was positive at the time of the first
      test. In 7 patients (3.8%) it became positive during treatment, and in 12
      patients (6 percent) the test remained negative until the end of study. There was
      no significant relationship between the skin lesion number and the positivity of
      the leishmanin skin test (p = 0.98). There was no significant relationship
      between age group and diameter of the induration. All of the patients who had
      negative leishmnanin test at the 12 months followup visit had one lesion only.
      CONCLUSION: This study showed that there is no relationship between age, gender,
      or duration of disease with positivity of the LST or degree of positivity, but
      there is a significant relationship with the clinical form of cutaneous
      leishmaniasis at the final test (12 patients). This study showed that there is no
      significant relationship between positivity of LST and the type of treatment.

PMID- 17459290
TI  - Psoriasis and hepatitis C treated with anti-TNF alpha therapy (etanercept).
AB  - The treatment of severe psoriasis in patients with concomitant hepatitis-C virus
      infection is quite difficult because several systemic anti-psoriatic drugs are
      contraindicated owing to their liver toxicity. Recent observations in the
      literature suggest that etanercept is an effective and safe therapy for this
      setting of patients. We present a 45-year-old man with extensive plaque psoriasis
      and concurrent hepatitis C, successfully treated with 12-month etanercept
      monotherapy. Regular controls of hepatic enzymes and viral load during the
      treatment disclosed no worsening of baseline values. This case confirms that
      etanercept may be a safe option for the therapy of patients with psoriasis and
      hepatitis-C virus infection.

PMID- 17459291
TI  - Dermatosis neglecta: a series of case reports and review of other dirty-appearing
      dermatoses.
AB  - Localized scaling and hyperpigmentation is a common finding and often a
      diagnostic and therapeutic challenge. Dermatosis neglecta (DN) represents a
      failure to adequately clean or scrub the skin, often in an area of hyperesthesia
      or prior trauma. We identified five cases of DN in two clinical practices in just
      the past few years. The condition is characterized by scrupulous avoidance of
      scrubbing, leading to a buildup of hyperpigmented, adherent, cornflake-like
      scales. An alcohol swabbing provided diagnosis and prompt clearing. Washing with
      soap and a washcloth also often leads to clearing. Dermatosis neglecta should be
      considered in the differential diagnosis of hyperpigmented scale; alcohol
      swabbing can serve as a diagnostic and therapeutic tool.

PMID- 17459292
TI  - Hidradenitis should not be renamed acne inversa.

PMID- 17459293
TI  - Recent immunologic considerations regarding the itch and treatment of scabies.
AB  - Scabies continues to be a major public health problem. Recent findings reveal
      that these mites produce substances that modulate the host's immune response
      resulting in the latency period prior to symptoms. In terms of treatment, two
      cases of ivermectin resistance have come to fore in Australia in patients treated
      over fifty times with the agent. Additionally, work in the development of
      vaccination of hosts with antigenic midgut proteins of mites to control
      ectoparasitic infestations continues.

PMID- 17459294
TI  - The many faces of phytophotodermatitis.
AB  - Phytophotodermatitis is a common cutaneous phototoxic reaction produced by
      contact with a variety of plant substances, followed by sunlight exposure.
      Phytophotodermatits can simulate child abuse, impetigo, superficial lymphangitis,
      and larva migrans. The most frequent presentation is hyperpigmentation of the
      dorsum of the hands, but there are other less common findings such as blisters or
      lesions mimicking solar lentigines and melasma.

PMID- 17459295
TI  - Paederus dermatitis in Sierra Leone.
AB  - Paederus dermatitis, a type of irritant contact dermatitis attributed to a
      Staphylinid beetle, is prevalent in most parts of the world. We studied 50 cases
      of Paederus dermatitis at the United Nations Hospital at Koidu Sierra Leone (West
      Africa), over a period of 6 months from Oct 2003 to Mar 2004. The objectives of
      the study were to determine clinical patterns of dermatitis and its response to
      topical steroids, with and without antibiotics. Patients with a definite history
      of contact with the insect were included in the study. Amongst these, 14 of the
      more severe cases were treated with oral prednisolone or intralesional
      triamcinolone acetonide. The remainder of the 36 patients were divided in two
      equal groups A and B. Patients in Group A were treated with topical
      diflucortolone valerate 0.001 percent and oral cetirizine hydrochloride; patients
      in group B were given oral ciprofloxacin in addition. In 50 patients studied, 43
      (86%) were males and 7 (14%) were females. The neck was the most common site
      involved followed by face. Healing time ranged from 14 to 28 days and lesions in
      all the patients healed with residual dyschromia. Healing time was shorter in
      Group B patients in comparison with those in Group A. Paederus dermatitis in
      Sierra Leone is a relatively severe form of this dermatitis. The better response
      to a combination of topical steroids and oral antibiotics may indicate concurrent
      bacterial infection.

PMID- 17459296
TI  - Keratoderma hereditarium mutilans (Vohwinkel syndrome) in three siblings.
AB  - Vohwinkel syndrome or keratoderma hereditaria mutilans is a rare, diffuse,
      honeycombed, palmar and plantar keratosis usually accompanied by pseudoainhum
      near the distal interphalangeal creases. The syndrome is reported in three out of
      five siblings (two brothers and one sister), who developed this problem in early
      childhood.

PMID- 17459297
TI  - Treatment of mycosis fungoides using a 308-nm excimer laser: two case studies.
AB  - Early-stage mycosis fungoides (MF) is most commonly treated with skin-directed
      therapies such as topical steroids, phototherapy (broadband or narrowband UVB),
      photochemotherapy (psoralen plus UVA), topical nitrogen mustard, and total skin
      electron-beam irradiation. Recently, several small studies have demonstrated the
      efficacy of the 308-nm excimer laser in the treatment of early-stage MF. This
      xenon-chloride laser, which emits monochromatic excimer light at the 308-nm
      wavelength, has been approved by the Food and Drug Administration to treat
      psoriasis since 1997 and to treat vitiligo since 2001. We report two patients in
      which patch-stage MF was treated with a 308-nm excimer laser. Our findings
      confirm previous observations that the 308-nm excimer laser is a safe, effective,
      and well-tolerated therapy for early stage MF.

PMID- 17459298
TI  - Irritant contact dermatitis from exposure to povidone-iodine may resemble toxic
      epidermal necrolysis.

PMID- 17459299
TI  - Disseminated cutaneous nocardiosis mimicking cellulitis and erythema nodosum.
AB  - Infection with Nocardia asteroides is a rare, life-threatening infection, which
      is most commonly encountered in immunocompromised patients. Cutaneous involvement
      is usually seen with disseminated infection but may also occur as primary
      cutaneous nocardiosis. We present a case of an immunocompromised patient who
      presented with cellulitis of the right hand and disseminated subcutaneous nodules
      of the lower extremities resembling erythema nodosum. Cultures from both a skin
      biopsy of a subcutaneous nodule on the leg as well as a surgical specimen from
      the debridement of her hand grew Nocardia asteroides. The patient was treated
      successfully with trimethoprim-sulfamethoxazole. This case likely represents
      primary cutaneous nocardiosis with secondary dissemination, which has been rarely
      reported. It also emphasizes that nocardial infection should be considered in the
      differential diagnosis of lesions suggestive of cellulitis or erythema nodosum in
      the severely immunocompromised patient.

PMID- 17459300
TI  - Granuloma inguinale: a case report.
AB  - Granuloma inguinale is common in certain regions of the world, however, it is
      rarely reported in the United States. It is the result of infection by
      Calymmatobacterium granulomati, although current literature proposes to re
      classify this organism as Klebsiella granulomati. Here we report a case of
      granuloma inguinale, review the literature, and discuss historical context,
      treatment options, and differential diagnosis.

PMID- 17459301
TI  - Three cases of toxic skin eruptions associated with methotrexate and a
      compilation of methotrexate-induced skin eruptions.
AB  - Methotrexate is an antimetabolite used as a treatment for a variety of neoplastic
      and inflammatory diseases. It has a variety of cutaneous side effects, in
      particular when administered in high doses. This is a report of cutaneous
      eruptions in three patients treated with methotrexate and a review of eruptions
      linked to methotrexate.

PMID- 17459303
TI  - Widespread Blaschkoid lichen planus.

PMID- 17459302
TI  - Generalized granuloma annulare resolving to anetoderma.
AB  - Granuloma annulare is a benign, degenerative skin disease; the generalized form
      is rare. The question of an association between generalized granuloma annulare
      and other internal diseases has been a matter of debate for many years. In this
      report, we present a 54-year-old latent diabetic patient with generalized
      granuloma annulare who developed anetoderma during its treatment.

PMID- 17459304
TI  - Perianal Crohn disease.
AB  - Crohn disease is a chronic inflammatory disease characterized by sharply
      demarcated segments of gastrointestinal involvement from mouth to anus. Its
      perineal manifestations are among the most devastating and mutilating
      complications. They occur at any time and may precede the intestinal
      manifestations. Their most common presentations are perineal ulceration, fistula,
      and abscess. Proliferative and polypoid morphology of the cutaneous lesions
      mimicking warts and condyloma are rarely described. We report a 25-year-old woman
      with a 4-month history of confluent plaques of the perineal region with vegetant
      surfaces, suspected to be genital warts. The lesions progressed to fistulas,
      inducing deep ulcerations surrounded by pseudocondylomatous tumors. About 2
      months prior to presentation she began to suffer from gastrointestinal symptoms
      and noted weight loss. Physical examination, endoscopic examination, and
      pathological interpretation led to the diagnosis of Crohn disease with perineal
      involvement being the initial presenting sign. Significant improvement was
      induced with prednisone (45 mg daily) and azathioprine. Our observation is
      notable for the pseudocondylomatous appearance and the dramatic response to
      medical treatment despite severe involvement.

PMID- 17459305
TI  - Seborrheic keratosis with in-situ squamous cell carcinoma changes.

PMID- 17459306
TI  - Granulomatous slack skin.

PMID- 17459307
TI  - Cerebriform nevus sebaceus: a rare entity.
AB  - We present a case of cerebriform nevus sebaceus in an 18-year-old boy. This form
      of nevus sebaceus is quite rare, in contrast to the relatively common linear
      variant.

PMID- 17459308
TI  - Segmental neurofibromatosis in association with a large congenital nevus and
      malignant melanoma.
AB  - We describe a patient with segmental neurofibromatosis and a large congenital
      nevus who developed malignant melanoma in the same anatomic distribution. The
      overlapping presentation suggests a common etiologic link between
      neurofibromatosis and large congenital nevi and the possibility that
      neurofibromatosis increases the risk of melanoma with large congenital nevi.

PMID- 17459309
TI  - Calcinosis cutis complicating liver transplantation.
AB  - We report a case of calcinosis cutis in a 41-year-old man developing after liver
      transplantation at sites where no intravenous calcium had been administered. The
      cutaneous lesions developed on his right upper arm 10-days post-transplantation.
      The patient had received calcium chloride solution intravenously after surgery.
      We excluded other causes of ectopic calcification such as hyperparathyroidism,
      renal failure, and extravasation of calcium chloride.

PMID- 17459310
TI  - Ulcus cruris associated with prolidase deficiency.
AB  - Prolidase deficiency is an autosomal recessive disorder that is associated with
      chronic cutaneous ulcers, mental retardation, unusual facial appearance, skeletal
      deformities, joint dislocations, hematological anomalies, splenomegaly, and
      chronic infections. The most typical finding is chronic, recurrent leg ulcers
      appearing in early childhood. Prolidase (peptidase-D) is necessary for collagen
      biosynthesis and its deficiency leads to impairment in connective tissue of the
      skin, capillaries, and lymphatic vessels. We report a 33-year-old woman who had a
      15-year history of nonhealing ulcer on left pretibial region accompanied by
      splenomegaly, hypochromic microcytic anemia, and thrombocytopenia. Prolidase
      deficiency is a rare genodermatosis and must be considered in the differential
      diagnosis of leg ulcers that develop at an early age.

PMID- 17459311
TI  - Neonatal lupus.
AB  - An otherwise healthy 5-week-old infant with erythematous plaques predominantly on
      the face and scalp presented to our dermatology clinic. The mother had been
      diagnosed with lupus erythematosus 2 years earlier but her disease was quiescent.
      Neonatal lupus is a rare condition associated with transplacental transfer of IgG
      anti-SSA/Ro and anti-SSB/La antibodies from the mother to the fetus. Active
      connective tissue disease in the mother does not have to be present and in fact
      is often absent. Although the cutaneous, hematologic and hepatic manifestations
      are transient, the potential for permanent heart block makes it necessary for
      this to be carefully ruled out. As in this case, the dermatologist may be the one
      to make the diagnosis and should be aware of the clinical presentation, work-up,
      and management of this important disease.

PMID- 17459312
TI  - Multiple infiltrated nodules and plaques. Lymphocytic infiltrate of Jessner.

PMID- 17459313
TI  - Papulosquamous dermatitis. Syphilis: a forgotten disease?
AB  - We report a case of secondary syphilis in a 54-year-old, bisexual, HIV positive
      man. Although syphilis is a well-known sexually-transmitted infection, it is not
      widely seen nowadays. However, a possible diagnosis of syphilis should not be
      overlooked in any individual, irrespective of HIV status.

PMID- 17459314
TI  - Methotrexate, hyperosmia, and migraine.

PMID- 17459315
TI  - Erythema nodosum leprosum: a presenting manifestation of lepromatous leprosy.

PMID- 17459316
TI  - Dietary macronutrient intake and five-year incident cataract: the blue mountains
      eye study.
AB  - PURPOSE: To investigate the relationships between dietary macronutrient intake at
      baseline and the five-year incidence of the three main types of cataract in older
      people. DESIGN: Population-based cohort study. METHODS:  SETTINGS: An urban
      community near Sydney, Australia. STUDY POPULATION: The Blue Mountains Eye Study
      (BMES) examined 3,654 predominantly Caucasian participants aged 49+ years during
      1992 to 1994, and then 2,335 survivors (71.5%) after five years. Of these 2,335
      subjects, 1988 (85%) completed a Willett-derived food frequency questionnaire
      (FFQ) at baseline. OBSERVATION PROCEDURES: A 145-item FFQ was used to assess
      nutrient intakes and lens photography was used to assess the presence of cataract
      at both time points. MAIN OUTCOME MEASURES: Incidence of cortical, nuclear, and
      posterior subcapsular (PSC) cataract was assessed via lens photographic grading
      following the Wisconsin cataract grading method. RESULTS: After adjusting for
      multiple known cataract risk factors, higher dietary intakes of omega-3
      polyunsaturated fatty acids (n-3 PUFA) were associated with a reduced incidence
      of nuclear cataract. The odds ratio (OR) for subjects in the highest quintile of
      intake compared to those in the lowest quintile was 0.58 (95% confidence interval
      [CI] 0.35 to 0.97), P(trend) = .027. Similarly, for PSC cataract, higher dietary
      intakes of protein were protective (OR 0.28; 95% CI 0.10 to 0.76), P(trend) =
      .015. Dietary macronutrient intake was not associated with incident cortical
      cataract. CONCLUSIONS: Higher dietary intakes of n-3 PUFA may decrease the five
      year risk of nuclear cataract, whereas higher dietary intakes of protein may
      decrease risk for PSC cataract.

PMID- 17459317
TI  - Factors influencing outcomes in cultivated limbal epithelial transplantation for
      chronic cicatricial ocular surface disorders.
AB  - PURPOSE: To analyze factors influencing clinical outcomes in cultivated limbal
      epithelial transplantation (CLET). DESIGN: Retrospective, observational case
      series. METHODS: Twenty-seven eyes of 27 patients that had CLET for severe
      chronic cicatricial ocular surface disorders were studied. Two different
      cultivation methods were used to prepare epithelial sheets. Method 1 used the
      explant technique and neither feeder cells nor air-lifting were used. In Method
      2, cell suspension technique and 3T3 feeder cells were used, and air-lifting was
      applied after cultivated cells became confluent. Clinical outcomes including
      corneal surface epithelialization and incidence of postoperative complications
      were studied. The relationship between the clinical outcome and type of
      cultivation method, original diseases, tear function, or preoperative ocular
      surface status was also studied. RESULTS: Both cultivation methods produced
      transplantable epithelial sheets with corneal phenotype. With a mean follow-up
      period of 127 weeks, corneal epithelialization was achieved in 16 eyes (59.3%).
      Eyes that had CLET with Method 1 suffered more severe postoperative complications
      such as infection, ulceration, and perforation (P = .053). Eyes with Stevens
      Johnson syndrome (SJS) had poor final corneal epithelialization compared with
      other diseases (P = .034). CLET was more successful when performed to
      conjunctivalized corneas compared with eyes with persistent epithelial defects or
      with dermalized corneas. CONCLUSIONS: CLET offers new treatment modalities to
      chronic cicatricial ocular surface disorders with moderate success rates. The
      treatment is feasible for eyes with non-immune-mediated disorders with stable
      ocular surface conditions. Epithelial sheets with better structural integrity
      seem to be superior to obtain early postoperative epithelialization and to avoid
      serious postoperative complications.

PMID- 17459318
TI  - Intravitreal bevacizumab (avastin) for choroidal neovascularization secondary to
      central serous chorioretinopathy, secondary to punctate inner choroidopathy, or
      of idiopathic origin.
AB  - PURPOSE: To evaluate the safety and efficacy of intravitreal bevacizumab in the
      treatment of idiopathic choroidal neovascularization (CNV) and CNV secondary to
      central serous chorioretinopathy (CSC) or punctate inner choroidopathy (PIC).
      DESIGN: Prospective, nonrandomized, interventional case series. METHODS: In an
      institutional clinical practice, 15 patients were recruited; nine had idiopathic
      CNV, two had CNV secondary to CSC, and four had CNV attributable to PIC. Patients
      received three monthly 1.25-mg intravitreal bevacizumab injections for three
      months. Patients were followed for six months, and the best-corrected visual
      acuity (BCVA), fluorescein angiography (FA) findings, and optical coherence
      tomography (OCT) central foveal thickness (CFT) were assessed. RESULTS: At
      baseline, the mean logMAR BCVA was 0.48 (Snellen equivalent = 20/60). The mean
      logMAR BCVA improved significantly to 0.25 (Snellen equivalent = 20/36) and 0.17
      (Snellen equivalent = 20/30) at one and six months, respectively (both P = .001).
      The mean OCT CFT reduced from 306 microm at baseline to 201 microm at six months
      (P < .001). All eyes (100%) had visual improvement of 1 line or more at six
      months, and 11 (73.3%) improved by 2 or more lines. FA showed absence of CNV
      leakage, the angiographic end point, at three months, and no recurrence was
      observed at six months in all eyes. No systemic or ocular adverse events were
      encountered. CONCLUSIONS: Intravitreal bevacizumab injections resulted in visual
      and anatomic improvements in eyes with idiopathic CNV and CNV attributable to CSC
      or PIC. Further studies are warranted to assess the long-term safety and the
      regimen for optimal efficacy of intravitreal bevacizumab.

PMID- 17459319
TI  - Multiplexing G protein-coupled receptors in microarrays: a radioligand-binding
      assay.
AB  - Multiplexing of G protein-coupled receptors (GPCRs) in microarrays promises to
      increase the efficiency, reduce the costs, and improve the quality of high
      throughput assays. However, this technology is still nascent and has not yet
      achieved the status of "high throughput" or laid claim to handling a large set of
      receptors. In addition, the technology has been demonstrated only when using
      fluorescent ligands to detect binding, limiting its application to a subset of
      GPCRs. To expand the impact of multiplexing on this receptor class, we have
      developed a radiometric approach to the microarray assay. In these studies, we
      considered two receptors in the alpha-adrenergic receptor family, alpha2A and
      alpha2C, and the 125I-labeled agonist clonidine. We demonstrate that microarrays
      of these receptors can be readily detected (signal/noise ratio approximately 160)
      using a Typhoon 9210 PhosphorImager. In addition, biochemical characterization
      shows that ligand-binding profiles and selectivity are preserved with the
      selective antagonists BRL44408 and ARC239. Importantly, these microarrays use
      approximately 200- to 400-fold less membrane preparation required by conventional
      assay methods and allow two or more receptors to be assayed in an area equivalent
      to a standard well of a microtiter plate. The impact of this approach on
      screening in drug discovery is discussed.

PMID- 17459320
TI  - Label-free immunosensing for alpha-fetoprotein in human plasma using surface
      plasmon resonance.
AB  - In this study, we attempted to develop a surface plasmon resonance (SPR)-based
      immunoassay sensor to detect alpha-fetoprotein (AFP) in human plasma at the
      nanogram level, as is required for clinical diagnosis of hepatocellular tumors. A
      self-assembled monolayer (SAM) surface of tri(ethylene glycol) (TEG) and carboxyl
      group-terminated hexa(ethylene glycol) (HEG) was employed to suppress the
      nonspecific adsorption of plasma components onto the sensor surface. AFP was
      detected by a sandwich-type immunoassay using two kinds of antibodies, primary
      and secondary, in this system. The SPR signal shift was further enhanced by
      applying an antibody (polyclonal) against the second antibody. With this method,
      the SPR signals were highly intensified, and so nanogram levels (ng/ml) of AFP
      could be easily detected with a high signal/noise ratio, as is necessary for
      clinical diagnosis. It is expected that our SPR-based immunoassay method can also
      be applicable to the detection of several other tumor markers that are present in
      low concentrations in human blood.

PMID- 17459321
TI  - Analytical method for detection of beta-amylase isozymes in dehydrated cucumber
      cotyledons by using two-dimensional polyacrylamide gel electrophoresis.

PMID- 17459322
TI  - Field evaluation of a new grocery checkstand design.
AB  - A novel express checkstand with basket cut-out was developed and evaluated in a
      small grocery store chain. Eight checkers performed three trials of simulated
      grocery checkout work with actor customers using both old and new checkstand
      designs. Usability was assessed by survey, structured interview and observation.
      Time-motion video analysis was used to evaluate differences in body postures,
      motions, and productivity. The new express checkstand design, which lowered and
      angled the presentation of the grocery basket, significantly (p<0.05) reduced
      right wrist flexion duration and repetition, and right arm elevation repetition.
      No significant differences were found in job cycle time between designs. These
      results demonstrate the utility of a new express checkstand design that could
      reduce extreme postures and motions with no loss in productivity.

PMID- 17459323
TI  - Reaction mechanisms of 15-hydroperoxyeicosatetraenoic acid catalyzed by human
      prostacyclin and thromboxane synthases.
AB  - Prostacyclin synthase (PGIS) and thromboxane synthase (TXAS) are atypical
      cytochrome P450s. They do not require NADPH or dioxygen for isomerization of
      prostaglandin H(2) (PGH(2)) to produce prostacyclin (PGI(2)) and thromboxane A(2)
      (TXA(2)). PGI(2) and TXA(2) have opposing actions on platelet aggregation and
      blood vessel tone. In this report, we use a lipid hydroperoxide, 15
      hydroperoxyeicosatetraenoic acid (15-HPETE), to explore the active site
      characteristics of PGIS and TXAS. The two enzymes transformed 15-HPETE not only
      into 13-hydroxy-14,15-epoxy-5,8,11-eicosatrienoic acid (13-OH-14,15-EET), like
      many microsomal P450s, but also to 15-ketoeicosatetraenoic acid (15-KETE) and 15
      hydroxyeicosatetraenoic acid (15-HETE). 13-OH-14,15-EET and 15-KETE result from
      homolytic cleavage of the O-O bond, whereas 15-HETE results from heterolytic
      cleavage, a common peroxidase pathway. About 80% of 15-HPETE was homolytically
      cleaved by PGIS and 60% was homolytically cleaved by TXAS. The V(max) of
      homolytic cleavage is 3.5-fold faster than heterolytic cleavage for PGIS
      catalyzed reactions (1100 min(-1)vs. 320 min(-1)) and 1.4-fold faster for TXAS
      (170 min(-1)vs. 120 min(-1)). Similar K(M) values for homolytic and heterolytic
      cleavages were found for PGIS ( approximately 60 microM 15-HPETE) and TXAS (
      approximately 80 microM 15-HPETE), making PGIS a more efficient catalyst for the
      15-HPETE reaction.

PMID- 17459324
TI  - Inactivation of cysteine and serine proteases by singlet oxygen.
AB  - The reaction of singlet oxygen with individual proteins is less well understood
      than that with other biological molecules. The inhibition of caspase 3 by singlet
      oxygen appears to involve the modification of a catalytic cysteine residue, since
      the reactivity of the sulfhydryl with alkylating agents decreased after singlet
      oxygen treatment. In addition to three cysteine proteases, two serine proteases
      were also found to be inhibited by singlet oxygen with a similar dose dependency,
      while an aspartate protease and a metalloprotease were not affected. The carbonyl
      content of these enzymes was elevated as the result of treatment with singlet
      oxygen. The catalytic center in serine proteases and cysteine proteases, in which
      catalytic reactions are based on similar mechanisms involving nucleophilic
      catalysis assisted by histidine as a general acid/base, can be expected to be
      modified by singlet oxygen and undergo inactivation.

PMID- 17459325
TI  - Survival of priceless cells: active and passive protection of embryonic stem
      cells against immune destruction.
AB  - This review focuses on our current knowledge of the mechanisms employed by
      embryonic stem (ES) cells to avoid destruction by cell-mediated immune responses.
      Recently, ES cells have been found to shield themselves against cytotoxic
      effector cells by expressing CD95L and serine protease inhibitor SPI-6 mediating
      apoptosis of the cytotoxic cells and inactivation of granzyme B, respectively.
      These findings are discussed in view of their implications for using ES cell
      derived transplants in regenerative medicine as well as for our understanding of
      early embryonic stages during invasion and implantation.

PMID- 17459326
TI  - Investigating the roles of putative active site residues in the oxalate
      decarboxylase from Bacillus subtilis.
AB  - Oxalate decarboxylase (OxDC) catalyzes the conversion of oxalate into CO(2) and
      formate using a catalytic mechanism that remains poorly understood. The Bacillus
      subtilis enzyme is composed of two cupin domains, each of which contains Mn(II)
      coordinated by four conserved residues. We have measured heavy atom isotope
      effects for a series of Bacillus subtilis OxDC mutants in which Arg-92, Arg-270,
      Glu-162, and Glu-333 are conservatively substituted in an effort to define the
      functional roles of these residues. This strategy has the advantage that observed
      isotope effects report directly on OxDC molecules in which the active site
      manganese center(s) is (are) catalytically active. Our results support the
      proposal that the N-terminal Mn-binding site can mediate catalysis, and confirm
      the importance of Arg-92 in catalytic activity. On the other hand, substitution
      of Arg-270 and Glu-333 affects both Mn(II) incorporation and the ability of Mn to
      bind to the OxDC mutants, thereby precluding any definitive assessment of whether
      the metal center in the C-terminal domain can also mediate catalysis. New
      evidence for the importance of Glu-162 in controlling metal reactivity has been
      provided by the unexpected observation that the E162Q OxDC mutant exhibits a
      significantly increased oxalate oxidase and a concomitant reduction in
      decarboxylase activities relative to wild type OxDC. Hence the reaction
      specificity of a catalytically active Mn center in OxDC can be perturbed by
      relatively small changes in local protein environment, in agreement with a
      proposal based on prior computational studies.

PMID- 17459327
TI  - Taurine deficiency and apoptosis: findings from the taurine transporter knockout
      mouse.
AB  - Apoptosis is characterized by cell shrinkage, nuclear condensation, DNA
      fragmentation and apoptotic body formation. Compatible organic osmolytes, e.g.
      taurine, modulate the cellular response to anisotonicity and may protect from
      apoptosis. Taurine transporter knockout mice (taut-/- mice) show strongly
      decreased taurine levels in a variety of tissues. They develop clinically
      important age-dependent diseases and some of them are characterized by apoptosis.
      Increased photoreceptor apoptosis leads to blindness of taut-/- mice at an early
      age. The taurine transporter may not be essential for the differentiation of
      photoreceptor cells, but many mature cells do not survive without an intact
      taurine transporter. The olfactory epithelium of taut-/- mice also exhibits
      structural and functional abnormalities. When compared with wild-types, taut-/-
      mice have a significantly higher proliferative activity of immature olfactory
      receptor neurons and an increased number of apoptotic cells. This is accompanied
      by electrophysiological findings indicating a reduced olfactory sensitivity.
      Furthermore, taut-/- and taut+/- mice develop moderate unspecific hepatitis and
      liver fibrosis beyond 1 year of age where hepatocyte apoptosis and activation of
      the CD95 system are pronounced.

PMID- 17459329
TI  - Impairment of the photosynthetic apparatus by oxidative stress induced by
      photosensitization reaction of protoporphyrin IX.
AB  - Treatment with the herbicide acifluorfen-sodium (AF-Na), an inhibitor of
      protoporphyrinogen oxidase, caused an accumulation of protoporphyrin IX (Proto
      IX) , light-induced necrotic spots on the cucumber cotyledon within 12-24 h, and
      photobleaching after 48-72 h of light exposure. Proto IX-sensitized and singlet
      oxygen ((1)O(2))-mediated oxidative stress caused by AF-Na treatment impaired
      photosystem I (PSI), photosystem II (PSII) and whole chain electron transport
      reactions. As compared to controls, the F(v)/F(m) (variable to maximal
      chlorophyll a fluorescence) ratio of treated samples was reduced. The PSII
      electron donor NH(2)OH failed to restore the F(v)/F(m) ratio suggesting that the
      reduction of F(v)/F(m) reflects the loss of reaction center functions. This
      explanation is further supported by the practically near-similar loss of PSI and
      PSII activities. As revealed from the light saturation curve (rate of oxygen
      evolution as a function of light intensity), the reduction of PSII activity was
      both due to the reduction in the quantum yield at limiting light intensities and
      impairment of light-saturated electron transport. In treated cotyledons both the
      Q (due to recombination of Q(A)(-) with S(2)) and B (due to recombination of
      Q(B)(-) with S(2)/S(3)) band of thermoluminescence decreased by 50% suggesting a
      loss of active PSII reaction centers. In both the control and treated samples,
      the thermoluminescence yield of B band exhibited a periodicity of 4 suggesting
      normal functioning of the S states in centers that were still active. The low
      temperature (77 K) fluorescence emission spectra revealed that the F(695) band
      (that originates in CP-47) increased probably due to reduced energy transfer from
      the CP47 to the reaction center. These demonstrated an overall damage to the PSI
      and PSII reaction centers by (1)O(2) produced in response to photosensitization
      reaction of protoporphyrin IX in AF-Na-treated cucumber seedlings.

PMID- 17459328
TI  - Energetics of heterotropic cooperativity between alpha-naphthoflavone and
      testosterone binding to CYP3A4.
AB  - Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of a majority of
      drugs. Heterotropic cooperativity of drug binding to CYP3A4 was examined with the
      flavanoid, alpha-naphthoflavone (ANF) and the steroid, testosterone (TST). UV-vis
      and EPR spectroscopy of CYP3A4 show that ANF binding to CYP3A4 occurs with
      apparent negative cooperativity and that there are at least two binding sites:
      (1) a relatively tight spin-state insensitive binding site (CYP.ANF) and (2) a
      relatively low affinity spin-state sensitive binding site (CYP.ANF.ANF). Since
      binding to the spin-state insensitive binding site is considerably tighter for
      ANF than TST, the spin-state insensitive binding site could be occupied by ANF,
      while titrating TST at the other site(s). The spin-state insensitive binding site
      of ANF appears to compete with the spin-state insensitive binding site of TST.
      The formation of the spin-state insensitive CYP.ANF complex is strongly
      temperature dependent, when compared to the formation of the CYP.TST complex,
      suggesting that the formation of the CYP3A4.ANF complex leads to long-range
      conformational changes within the protein. When the CYP.ANF complex is titrated
      with TST, the formation of CYP.ANF.TST is favored by 3:1 over the formation of
      CYP.TST.TST, suggesting that there is an allosteric interaction between ANF and
      TST. A model of heterotropic cooperativity of CYP3A4 is presented, where the spin
      state insensitive binding of ANF occurs at the same peripheral binding site of
      CYP3A4 as TST.

PMID- 17459330
TI  - Dependence of reaction center-type energy-dependent quenching on photosystem II
      antenna size.
AB  - The effects of photosystem II antenna size on reaction center-type energy
      dependent quenching (qE) were examined in rice plants grown under two different
      light intensities using both wild type and qE-less (OsPsbS knockout) mutant
      plants. Reaction center-type qE was detected by measuring non-photochemical
      quenching at 50 micromol photons m(-2) s(-1) white light intensity. We observed
      that in low light-grown rice plants, reaction center-type qE was higher than in
      high light-grown plants, and the amount of reaction center-type qE did not depend
      on zeaxanthin accumulation. This was confirmed in Arabidopsis npq1-2 mutant
      plants that lack zeaxanthin due to a mutation in the violaxanthin de-epoxidase
      enzyme. Although the electron transport rate measured at a light intensity of 50
      micromol photons m(-2) s(-1) was the same in high light- and low light-grown wild
      type and mutant plants lacking PsbS protein, the generation of energy-dependent
      quenching was completely impaired only in mutant plants. Analyses of the pigment
      content, Lhcb proteins and D1 protein of PSII showed that the antenna size was
      larger in low light-grown plants, and this correlated with the amount of reaction
      center-type qE. Our results mark the first time that the reaction center-type qE
      has been shown to depend on photosystem II antenna size and, although it depends
      on the existence of PsbS protein, the extent of reaction center-type qE does not
      correlate with the transcript levels of PsbS protein. The presence of reaction
      center-type energy-dependent quenching, in addition to antenna-type quenching, in
      higher plants for dissipation of excess light energy demonstrates the complexity
      and flexibility of the photosynthetic apparatus of higher plants to respond to
      different environmental conditions.

PMID- 17459331
TI  - Molecular rearrangement in POR macrodomains as a reason for the blue shift of
      chlorophyllide fluorescence observed after phototransformation.
AB  - The activation energy and activation volume of the spectral blue shift subsequent
      to protochlorophyllide phototransformation (called Shibata shift in intact
      leaves) were studied in prolamellar body (PLB) and prothylakoid-(PT)-enriched
      membrane fractions prepared from dark-grown wheat (Triticum aestivum, L.) leaves.
      The measurements were done at 20, 30 and 40 degrees C and at various pressure
      values. The activation energy values were 181+/-8 kJ mol(-1) and 188+/-6 kJ mol(
      1) for the PLBs and the PTs, respectively. The pressure stabilized the structure
      of the NADPH:protochlorophyllide oxidoreductase (POR) macrodomains; it prevented
      or slowed down the blue shift. There were no significant differences between the
      activation volumes of PLBs and PTs at 30 or 40 degrees C giving values around 100
      125 ml mol(-1) which correspond to changes in the tertiary structure of proteins
      but also resemble the volume changes occurring during the disaggregation of
      protein dimers or oligomers, or during dissociation of peripheral membrane
      proteins from membranes. The small differences in the activation parameters of
      PLBs and PTs indicate that molecular rearrangements inside the POR macrodomains
      are the primary reasons of the fluorescence blue shift; however, their lipid
      microenvironment must be also important in the initialization of the shift.

PMID- 17459332
TI  - Galactosyl headgroup interactions control the molecular packing of wheat lipids
      in Langmuir films and in hydrated liquid-crystalline mesophases.
AB  - The behavior of the two major galactolipids of wheat endosperm, mono- (MGDG) and
      di-galactosyldiacylglycerol (DGDG) was studied in aqueous dispersion and at the
      air/liquid interface. The acyl chains of the pure galactolipids and their binary
      equimolar mixture are in the fluid or liquid expanded phase. SAXS measurements on
      liquid-crystalline mesophases associated with the electron density
      reconstructions show that the DGDG adopts a lamellar phase L(alpha) with parallel
      orientation of the headgroups with respect to the plane of the bilayer, whereas
      MGDG forms an inverse hexagonal phase H(II) with a specific organization of
      galactosyl headgroups. The equimolar mixture shows a different behavior from
      those previously described with formation of an Im3m cubic phase. In comparing
      monolayers composed of the pure galactolipids and their equimolar mixtures, PM
      IRRAS spectra show significant differences in the optical properties and
      orientation of galactosyl groups with respect to the interface. Furthermore,
      Raman and FTIR spectroscopies show that the acyl chains of the galactolipid
      mixture are more ordered compared to those of the pure components. These results
      suggest strong interactions between MGDG and DGDG galactosyl headgroups and these
      specific physical properties of galactolipids are discussed in relation to their
      biological interest in wheat seed.

PMID- 17459333
TI  - Deteriorating memory confidence, responsibility perceptions and repeated
      checking: comparisons in OCD and control samples.
AB  - Repeated checking has been repeatedly associated with memory distrust. We sought
      to extend previous research using a computer-based checking task by incorporating
      a group of 15 individuals with OCD, and examining the effect of increased
      perceived responsibility. Participants were asked to repeatedly check a virtual
      stovetop, with half the participants also placed under a condition of high
      perceived responsibility. Our observations replicated previous research showing
      that the act of repeatedly checking leads to reductions in memory vividness,
      detail and confidence, without accompanying reductions in memory accuracy.
      Furthermore, while a sense of increased personal responsibility had little effect
      on a student control sample, it led to a significant further deterioration in
      memory confidence in individuals with OCD. These results suggest that in people
      with OCD, normal reductions in memory confidence over repeated trials are
      exacerbated and intensified by inflated responsibility perceptions.

PMID- 17459334
TI  - A high-throughput method for monitoring changes in homeobox gene expression.
AB  - Members of the homeobox gene superfamily of transcription factors are essential
      determinants of cellular identity during development. Their regulation and
      downstream gene targets are not well understood, however. This is due, in part,
      to the large number of genes that need to be analyzed simultaneously. A method
      has been developed for the rapid and simultaneous detection of changes in the
      expression of homeobox-containing genes, including members of the developmentally
      important Hox gene family. The method selectively amplifies and labels homeobox
      containing mRNAs using a 3'-RACE procedure in combination with a degenerate
      forward primer that targets a highly conserved region of the homeobox found in
      all vertebrate Hox genes and many non-Hox homeobox-containing genes. The
      amplified sequences are identified by hybridization to a membrane-based array of
      covalently bound Hox and non-Hox homeobox gene sequences of interest. The method
      has been used here to demonstrate previously undetected changes in the expression
      of homeobox genes during retinoic acid-induced nerve cell differentiation in
      mouse pluripotent P19 cells.

PMID- 17459335
TI  - Gas6, a new regulator of chondrogenic differentiation from mesenchymal cells.
AB  - The mesenchymal cell line C3H10T1/2 can be preferentially induced toward
      chondrogenesis by culturing as a micromass in the presence of bone morphogenetic
      protein 2. To screen new regulator genes for chondrogenic differentiation, we
      performed differential display polymerase chain reaction and identified growth
      arrest-specific 6 (Gas6) as a gene that was clearly downregulated by this
      induction of chondrogenic differentiation. Blockage of Gas6 mRNA expression by
      siRNA remarkably enhanced the chondrogenic differentiation, while stimulation
      with recombinant Gas6 inhibited the mRNA expressions of type II collagen (Col2a1)
      and aggrecan. Gas6 signaling activated the phosphorylation of ERK1/2, SAPK/JNK,
      and Akt, but not p38 MAPK. These results suggest that Gas6 negatively regulates
      chondrogenic differentiation, at least through the MAPK pathway.

PMID- 17459336
TI  - Syntaxin6 separates from GM1a-rich membrane microdomain during granule
      maturation.
AB  - Since it was reported that components of immature secretory granules (ISGs) are
      different from those of mature secretory granules (MSGs) in rat parotid acinar
      cells, we have been considering that components of secretory granules (SGs)
      change dynamically during granule maturation. As the first step to understand the
      mechanism of granule maturation, we separated low-density detergent-resistant
      membrane fractions (DRMs) from purified SGs of rat parotid gland. When SGs were
      lysed by the detergent Brij-58, syntaxin6 and VAMP4 were found in DRMs that were
      different from the GM1a-rich DRMs containing VAMP2. Because syntaxin6 and VAMP4
      are known to be related to granule formation, we attempted to separate DRMs from
      ISGs. To enrich for ISGs, glands were removed from rats 5h after intraperitoneal
      injection of isoproterenol and used to purify the newly synthesized granules.
      Compared to mature granules prepared without injection, these newly formed
      granules were lower in density and contained higher concentrations of syntaxin6,
      VAMP4, and gamma-adaptin. This composition is consistent with the
      characterizations of ISGs. DRMs isolated from the newly formed granules were GM1a
      rich and contained syntaxin6, VAMP4, and VAMP2 together. Thus, our findings
      suggest that syntaxin6 and VAMP4 associate with a GM1a-rich membrane microdomain
      during granule formation but enter a separate membrane microdomain before
      transport from granules during maturation.

PMID- 17459337
TI  - Complement activation by islet amyloid polypeptide (IAPP) and alpha-synuclein
      112.
AB  - Complement can damage host tissue when overactivated. Evidence of complement self
      damage exists for Alzheimer disease (AD), age-related macular degeneration, type
      1 diabetes mellitus (T1DM), and Parkinson disease (PD). Known complement
      activators include Abeta, found in AD, and IgG found in T1DM. We compared their
      complement activating ability in vitro with those of islet amyloid polypeptide
      (IAPP), which aggregates in the pancreas of T2DM, and alpha-synuclein (alpha
      Syn), which aggregates in PD. We found that IAPP and the alternatively spliced
      alpha-Syn 112 form, but not full-length alpha-Syn 140, activated complement in
      vitro. Complement activation may contribute to death of insulin-secreting cells
      in T2DM or to neuronal death in Parkinson disease (PD) and related
      synucleinopathies where alpha-Syn 112 occurs. This suggests the possibility of
      anti-inflammatory treatment in these pathologies. It also suggests that blockers
      of complement activation may be an appropriate therapeutic target for a range of
      age-related degenerative diseases.

PMID- 17459338
TI  - The formation of hydrogen bond in the proximal heme pocket of HemAT-Bs upon
      ligand binding.
AB  - HemAT-Bs is the heme-based O(2) sensor responsible for aerotaxis control in
      Bacillus subtilis. In this study, we measured the time-resolved resonance Raman
      spectra of full-length HemAT-Bs wild-type (WT) and Y133F in the deoxy form and
      the photoproduct after photolysis of CO-bound form. In WT, the nu(Fe-His) band
      for the 10 ps photoproduct was observed at higher frequency by about 2 cm(-1)
      compared with that of the deoxy form. This frequency difference is relaxed in
      hundreds of picoseconds. This time-dependent frequency shift would reflect the
      conformational change of the protein matrix. On the other hand, Y133F mutant did
      not show such a substantial nu(Fe-His) frequency shift after photolysis. Since a
      hydrogen bond to the proximal His induces an up-shift of the nu(Fe-His)
      frequency, these results indicate that Tyr133 forms a hydrogen bond to the
      proximal His residue upon the ligand binding. We discuss a functional role of
      this hydrogen bond formation for the signal transduction in HemAT-Bs.

PMID- 17459339
TI  - Phosphorylation of APP695 at Thr668 decreases gamma-cleavage and extracellular
      Abeta.
AB  - Phosphorylation of human APP695 at Thr668 seems to be specific to neuronal tissue
      and could affect Abeta production. Metabolism of APP mutated at Thr668 residue
      was analyzed in CHO cell line and primary cultures of rat cortical neurons. By
      site-directed mutagenesis, T668A or T668D substitutions were introduced in wild
      type APP695. In CHO cells, wild-type APP695 was very slightly phosphorylated at
      Thr668 and produced similar levels of extracellular Abeta40 as compared to
      APPT668A. On the contrary, APPT668D was more efficiently cleaved by beta
      secretase. However, accumulated betaCTF were less cleaved by gamma-secretase and
      less extracellular Abeta40 was produced. Decreased susceptibility to cleavage by
      gamma-secretase was confirmed upon expression of C99T668D. In neurons, part of
      APP695 was phosphorylated at Thr668. Following neuronal expression of APPT668A,
      extracellular Abeta40 production was increased. In conclusion, phosphorylation of
      human APP695 at Thr668 increases APP beta-cleavage but decreases its gamma
      cleavage and extracellular Abeta40 production.

PMID- 17459340
TI  - Cell cycle effect on the activity of deoxynucleoside analogue metabolising
      enzymes.
AB  - Deoxynucleoside analogues (dNAs) are cytotoxic towards both replicating and
      indolent malignancies. The impact of fluctuations in the metabolism of dNAs in
      relation to cell cycle could have strong implications regarding the activity of
      dNAs. Deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK) are important
      enzymes for phosphorylation/activation of dNAs. These drugs can be
      dephosphorylated/deactivated by 5'-nucleotidases (5'-NTs) and elevated activities
      of 5'-NTs and decreased dCK and/or dGK activities represent resistance mechanisms
      towards dNAs. The activities of dCK, dGK, and three 5'-NTs were investigated in
      four human leukemic cell lines in relationship to cell cycle progression and
      cytotoxicity of dNAs. Synchronization of cell cultures to arrest in G0/G1 by
      serum-deprivation was performed followed by serum-supplementation for cell cycle
      progression. The activities of dCK and dGK increased up to 3-fold in CEM, HL60,
      and MOLT-4 cells as they started to proliferate, while the activity of cytosolic
      nucleotidase I was reduced in proliferating cells. CEM, HL60, and MOLT-4 cells
      were also more sensitive to cladribine, cytarabine, 9-beta-D
      arabinofuranosylguanine and clofarabine than K562 cells which demonstrated lower
      levels and less alteration of these enzymes and were least susceptible to the
      cytotoxic effects of most dNAs. The results suggest that, in the cell lines
      studied, the proliferation process is associated with a general shift in the
      direction of activation of dNAs by inducing activities of dCK/dGK and reducing
      the activity of cN-I which is favourable for the cytotoxic effects of cladribine,
      cytarabine and, 9-beta-D-arabinofuranosylguanine. These results emphasize the
      importance of cellular proliferation and dNA metabolism by both phosphorylation
      and dephosphorylation for susceptibility to dNAs. It underscores the need to
      understand the mechanisms of action and resistance to dNAs in order to increase
      efficacy of dNAs treatment by new rational.

PMID- 17459341
TI  - Characterization of porcine arterial endothelial cells cultured on amniotic
      membrane, a potential matrix for vascular tissue engineering.
AB  - The existing of basement membrane improves the development of endothelium while
      constructing blood vessel equivalent. The amniotic membrane (AM) provides a
      natural basement membrane and has been used in ocular surface reconstruction.
      This study evaluated the molecular and cellular characteristics of porcine
      vascular endothelial cells (ECs) cultured on AM. ECs cultured on AM expressed the
      endothelial marker vWF and exhibited normal endothelial morphology. Here, we
      demonstrated that AM enhanced the expression of intercellular molecules, platelet
      endothelial cell adhesion molecule-1 (PECAM-1), and adhesion molecule VE-cadherin
      at the intercellular junctions. The expression level of integrin was markedly
      higher in ECs cultured on AM than on plastic dish. Furthermore, the AM
      downregulated the expression of E-selectin and P-selectin in both LPS-activated
      and non-activated ECs. Consistently, adhesion of leukocytes to both activated and
      non-activated cells was decreased in ECs cultured on AM. Our results suggest that
      AM is an ideal matrix to develop a functional endothelium in blood vessel
      equivalent construction.

PMID- 17459342
TI  - Aberrant hypermethylation of the FGFR2 gene in human gastric cancer cell lines.
AB  - We have previously shown that fibroblast growth factor receptor 2 (FGFR2) plays
      an important role in gastric carcinogenesis. In this study, we assessed DNA
      methylation status in the promoter region of FGFR2 gene in gastric cancer cell
      lines, and indicated that this region was highly methylated, compared with FGFR2
      expressing gastric cancer cell lines. Moreover, the restoration of FGFR2
      expression by treating methylated cells with the DNA methyltransferase inhibitor
      5-aza-2'-deoxycytidine strongly suggests that the loss of FGFR2 expression may be
      due to the aberrant hypermethylation in the promoter region of the FGFR2 gene.
      Thus, our results suggest that the epigenetic silencing of FGFR2 through DNA
      methylation in gastric cancer may contribute to tumor progression.

PMID- 17459343
TI  - Isolation of multipotent stem cells from adult rat periodontal ligament by
      neurosphere-forming culture system.
AB  - Adult multipotent stem cells have been isolated from various non-neural tissues.
      Here, we report the isolation of multipotent stem cells from rat periodontal
      ligament (PDL) using neurosphere-forming culture system. Enzymatically
      dissociated PDL cells were cultured in serum-free basal medium containing EGF,
      bFGF, and LIF. Free-floating spheres expressing nestin, GFAP, and vimentin were
      formed by 7 days of the culture. In addition, spheres expressed mRNA of neural
      crest-associated transcription factors Twist, Slug, Sox2, and Sox9. PDL-derived
      spheres differentiated into multinucleated myotubes, NFM-positive neuron-like
      cells, GFAP-positive astrocyte-like cells and CNPase-positive oligodendrocyte
      like cells. Methylcellulose colony-forming assay revealed that a single PDL cell
      could form a sphere at a frequency of approximately 0.01% of total cells. These
      data indicate that PDL-derived spheres contained multipotent adult stem cells
      capable of differentiating into both neural and mesodermal progeny. This is the
      first report of the isolation of PDL-derived stem cells with primitive neural
      crest stem cell features.

PMID- 17459344
TI  - Multiple priming of lexically ambiguous and unambiguous targets in the cerebral
      hemispheres: the coarse coding hypothesis revisited.
AB  - The coarse coding hypothesis postulates that the cerebral hemispheres differ in
      their breadth of semantic activation, with the left hemisphere activating a
      narrow, focused semantic field and the right weakly activating a broader semantic
      field. In support of coarse coding, studies investigating priming for multiple
      senses of a lexically ambiguous word have reported a right hemisphere benefit.
      However, studies of mediated priming have failed to find a right hemisphere
      advantage for processing distantly linked, unambiguous words. To address this
      debate, the present study made use of a multiple priming paradigm in which two
      primes either converged onto the single meaning of an unambiguous, lexically
      associated target (LION-STRIPES-TIGER) or diverged onto different meanings of an
      ambiguous target (KIDNEY-PIANO-ORGAN). In two experiments, participants either
      made lexical decisions to lateralized targets (Experiment 1) or made a semantic
      relatedness judgment between primes and targets (Experiment 2). In both tasks,
      for both ambiguous and unambiguous triplets we found equivalent priming strengths
      and patterns across the two visual fields, counter to the predictions of the
      coarse coding hypothesis. Priming patterns further suggested that both
      hemispheres made use of lexical level representations in the lexical decision
      task and semantic representations in the semantic judgment task.

PMID- 17459346
TI  - Short-term memory traces for action bias in human reinforcement learning.
AB  - Recent experimental and theoretical work on reinforcement learning has shed light
      on the neural bases of learning from rewards and punishments. One fundamental
      problem in reinforcement learning is the credit assignment problem, or how to
      properly assign credit to actions that lead to reward or punishment following a
      delay. Temporal difference learning solves this problem, but its efficiency can
      be significantly improved by the addition of eligibility traces (ET). In essence,
      ETs function as decaying memories of previous choices that are used to scale
      synaptic weight changes. It has been shown in theoretical studies that ETs
      spanning a number of actions may improve the performance of reinforcement
      learning. However, it remains an open question whether including ETs that persist
      over sequences of actions allows reinforcement learning models to better fit
      empirical data regarding the behaviors of humans and other animals. Here, we
      report an experiment in which human subjects performed a sequential economic
      decision game in which the long-term optimal strategy differed from the strategy
      that leads to the greatest short-term return. We demonstrate that human subjects'
      performance in the task is significantly affected by the time between choices in
      a surprising and seemingly counterintuitive way. However, this behavior is
      naturally explained by a temporal difference learning model which includes ETs
      persisting across actions. Furthermore, we review recent findings that suggest
      that short-term synaptic plasticity in dopamine neurons may provide a realistic
      biophysical mechanism for producing ETs that persist on a timescale consistent
      with behavioral observations.

PMID- 17459345
TI  - The chemokine CX3CL1/fractalkine interferes with the antinociceptive effect
      induced by opioid agonists in the periaqueductal grey of rats.
AB  - We have reported that there is heterologous interaction between the mu, delta or
      kappa opioid receptors and the receptors for the chemokines CCL5/RANTES or
      CXCL12/SDF-1 in the regulation of antinociception in rats. CX3CL1/fractalkine, a
      chemokine that exclusively binds to CX3CR1, has been found to affect morphine
      analgesia and tolerance in the spinal cord. The purpose of the present study was
      to see if the interaction between the chemokine CX3CL1/fractalkine receptor and
      mu, delta or kappa opioid receptors occurs in the periaqueductal grey (PAG) of
      adult male S-D rats. The cold-water tail-flick (CWT) test was used to measure
      antinociception. The results showed that intra-PAG injection of 100 ng
      CX3CL1/fractalkine 30 min before administration of 400 ng DAMGO, 100 ng DPDPE or
      20 microg dynorphin significantly reduced the antinociception induced by each of
      these peptides. These results demonstrate that activation of the CX3CL1 receptor
      diminishes the effect of mu, delta and kappa opioid agonists on their receptors
      in the PAG of rats.

PMID- 17459347
TI  - The effects of rate and sequence complexity on repetitive finger movements.
AB  - We studied the effects of movement rate and sequence complexity on the execution
      of externally paced finger movements. Simple thumb-index opposition movements
      (SEQ1), oppositions of thumb to index, medium, ring and little fingers (SEQ2),
      and oppositions of thumb to index, ring, medium and little fingers (SEQ3) were
      paced by a metronome at rates that ranged from 0.5 to 5 Hz. At rates higher than
      2.5 Hz touch duration, as well as spatial and timing accuracy changed, although
      with a different pattern, for the sequences. Delayed movements were mostly
      present at lowest rates in SEQ1; at 0.5 Hz and at frequencies higher than 3.5 Hz
      in SEQ2; at rates higher than 3.5 Hz in SEQ3. Syncopation occurred at rates
      higher than 3 Hz but only for SEQ2 and SEQ3 when movements are delayed. Power
      spectrum analysis of timing error series indicated that SEQ1 performance is
      influenced by memory-related processes at all movement rates. On the other hand,
      for the other two sequences, at rates higher than 4 Hz the timing error series
      exhibit a slight but significant reduction of its long-range correlation
      characteristics. These findings suggest that different strategies are used for
      sensorimotor processing when the movement rate and sequence complexity are
      increased.

PMID- 17459348
TI  - Regional brain differences in the effect of distraction during the delay interval
      of a working memory task.
AB  - Working memory (WM) comprises operations whose coordinated action contributes to
      our ability to maintain focus on goal-relevant information in the presence of
      distraction. The present study investigated the nature of distraction upon the
      neural correlates of WM maintenance operations by presenting task-irrelevant
      distracters during the interval between the memoranda and probes of a delayed
      response WM task. The study used a region of interest (ROIs) approach to
      investigate the role of anterior (e.g., lateral and medial prefrontal cortex-
      PFC) and posterior (e.g., parietal and fusiform cortices) brain regions that have
      been previously associated with WM operations. Behavioral results showed that
      distracters that were confusable with the memorandum impaired WM performance,
      compared to either the presence of non-confusable distracters or to the absence
      of distracters. These different levels of distraction led to differences in the
      regional patterns of delay interval activity measured with event-related
      functional magnetic resonance imaging (fMRI). In the anterior ROIs, dorsolateral
      PFC activation was associated with WM encoding and maintenance, and in
      maintaining a preparatory state, and ventrolateral PFC activation was associated
      with the inhibition of distraction. In the posterior ROIs, activation of the
      posterior parietal and fusiform cortices was associated with WM and perceptual
      processing, respectively. These findings provide novel evidence concerning the
      neural systems mediating the cognitive and behavioral responses during
      distraction, and places frontal cortex at the top of the hierarchy of the neural
      systems responsible for cognitive control.

PMID- 17459349
TI  - Neural correlates of human action observation in hearing and deaf subjects.
AB  - Accumulating evidence has suggested the existence of a human action recognition
      system involving inferior frontal, parietal, and superior temporal regions that
      may participate in both the perception and execution of actions. However, little
      is known about the specificity of this system in response to different forms of
      human action. Here we present data from PET neuroimaging studies from passive
      viewing of three distinct action types, intransitive self-oriented actions (e.g.,
      stretching, rubbing one's eyes, etc.), transitive object-oriented actions (e.g.,
      opening a door, lifting a cup to the lips to drink), and the abstract, symbolic
      actions-signs used in American Sign Language. Our results show that these
      different classes of human actions engage a frontal/parietal/STS human action
      recognition system in a highly similar fashion. However, the results indicate
      that this neural consistency across motion classes is true primarily for hearing
      subjects. Data from deaf signers shows a non-uniform response to different
      classes of human actions. As expected, deaf signers engaged left-hemisphere
      perisylvian language areas during the perception of signed language signs.
      Surprisingly, these subjects did not engage the expected frontal/parietal/STS
      circuitry during passive viewing of non-linguistic actions, but rather reliably
      activated middle-occipital temporal-ventral regions which are known to
      participate in the detection of human bodies, faces, and movements. Comparisons
      with data from hearing subjects establish statistically significant contributions
      of middle-occipital temporal-ventral during the processing of non-linguistic
      actions in deaf signers. These results suggest that during human motion
      processing, deaf individuals may engage specialized neural systems that allow for
      rapid, online differentiation of meaningful linguistic actions from non
      linguistic human movements.

PMID- 17459350
TI  - Spike-timing-dependent plasticity induced in resting lower limb cortex persists
      during subsequent walking.
AB  - Transcranial magnetic stimulation (TMS) of human lower limb motor cortex paired
      with common peroneal nerve electrical stimulation produces a lasting modulation
      of motor cortex excitability following the principles of spike-timing-dependent
      plasticity. We previously demonstrated that this "paired associative stimulation"
      (PAS) protocol applied during walking induced a bidirectional modulation of
      cortical excitability. The present study tested the hypothesis that the
      excitability of lower limb motor cortex assessed during walking is increased when
      PAS is applied to the resting cortex. PAS was delivered as a block of 120 pairs
      at 0.5 Hz to healthy subjects (n=13) in three separate sessions. TMS intensity
      was related to the active threshold obtained in tibialis anterior (TA) during the
      late swing phase of walking. Therefore, intensities used were below resting
      thresholds. When PAS using TMS intensities above active threshold was applied to
      the resting cortex, the normalized amplitude of potentials evoked in TA during
      subsequent walking increased to 124%. Using the same parameters and applying PAS
      during the late swing phase of walking, response amplitude increased to 114% of
      baseline. When the TMS intensity was set to active threshold, PAS applied to the
      resting cortex did not significantly modulate cortical excitability.

PMID- 17459351
TI  - Membrane properties and synaptic connectivity of fast-spiking interneurons in rat
      ventral striatum.
AB  - In vitro patch-clamp recordings were made to study the membrane properties and
      synaptic connectivity of fast-spiking interneurons in rat ventral striatum. Using
      a whole-cell configuration in acutely prepared slices, fast-spiking interneurons
      were recognized based on their firing properties and their morphological
      phenotype was confirmed by immunocytochemistry. Membrane properties of fast
      spiking interneurons were distinguished from those of medium-sized spiny neurons
      by their more depolarized resting membrane potential, lower action potential
      amplitude and shorter half-width, short spike repolarization time and deep spike
      afterhyperpolarization. Firing patterns of interneurons could be subdivided in a
      bursting and non-bursting mode. Simultaneous dual whole-cell recordings revealed
      a high degree of connectivity of fast-spiking interneurons to medium-sized spiny
      neurons via unidirectional synapses. Burst firing in fast-spiking interneurons
      that were presynaptic to medium-sized spiny neurons resulted in barrages of
      postsynaptic potentials showing an initial amplitude increment, rapidly followed
      by a decrement. In conclusion, ventral striatal fast-spiking interneurons can be
      clearly distinguished from medium-sized spiny neurons by their membrane
      properties and their firing patterns can be subdivided in bursting and non
      bursting modes. Their synaptic connectivity to medium-sized spiny neurons is
      unidirectional and characterized by frequency-dependent, dynamic changes in
      postsynaptic amplitude.

PMID- 17459352
TI  - Potentiation of neurogenesis and angiogenesis by G-CSF after focal cerebral
      ischemia in rats.
AB  - Recently, granulocyte colony-stimulating factor (G-CSF) is expected to
      demonstrate beneficial effects on cerebral ischemia. Here, we showed the
      potential benefit of G-CSF administration after transient middle cerebral artery
      occlusion (tMCAO). Adult male Wistar rats received vehicle or G-CSF (50
      microg/kg) subcutaneously after reperfusion, and were treated with 5
      bromodeoxyuridine (BrdU, 50 mg/kg) once daily by the intraperitoneal route for 3
      days after tMCAO. Nissl-stained sections at 7 days after tMCAO showed significant
      reduction of the infarction area (31%, P<0.01). At 7 days after tMCAO, BrdU plus
      NeuN double-positive cells increased by 43.3% in the G-CSF-treated group
      (P<0.05), and BrdU-positive endothelial cells were increased 2.29 times in the G
      CSF-treated group, to a level as high as that in the vehicle-treated group
      (P<0.01), in the periischemic area. Our results indicate that G-CSF caused
      potentiation of neuroprotection and neurogenesis and is expected to have
      practical therapeutic potential in treating individuals after ischemic brain
      injury.

PMID- 17459353
TI  - AM404 decreases Fos-immunoreactivity in the spinal cord in a model of
      inflammatory pain.
AB  - Cannabinoids, such as anandamide, are involved in pain transmission. We evaluated
      the effects of AM404 (N-(4-hydroxyphenyl)-5Z,8Z,11Z,14Z-eicosatetraenamide), an
      anandamide reuptake inhibitor, monitoring the expression of c-fos, a marker of
      activated neurons and the pain-related behaviours using formalin test. The study
      was carried out in an experimental model of inflammatory pain made by a single
      injection of formalin in rat hind paws. Formalin test showed that the
      antinociceptive effect of AM404 was evident in phase I. We found that Fos
      positive neurons in dorsal superficial and deep laminae of the lumbar spinal cord
      increased in formalin-injected animals and that AM404 significantly reduced Fos
      induction. Co-administration of cannabinoid CB(1) receptor antagonist (AM251),
      cannabinoid CB(2) receptor antagonist (AM630) and transient receptor potential
      vanilloid type 1 (TRPV-1) antagonist (capsazepine), attenuate the inhibitory
      effect of AM404 and this effect was higher using cannabinoid CB(2) and vanilloid
      TRPV-1 receptor antagonists. These results suggest that AM404 could be a useful
      drug to reduce inflammatory pain in our experimental model and that cannabinoid
      CB(2) receptor and vanilloid TRPV-1 receptor, and to a lesser extent, the
      cannabinoid CB(1) receptor are involved.

PMID- 17459354
TI  - Neprilysin protects neurons against Abeta peptide toxicity.
AB  - In recent years, studies have suggested that accumulation of amyloid beta (Abeta)
      peptide in the brain plays a key role in the development of Alzheimer's disease
      (AD). The steady-state level of Abeta peptide in the brain is determined by the
      rate of production from amyloid precursor protein (APP) via beta- and gamma
      secretases and degradation by the activity of several enzymes. Neprilysin (NEP)
      appears to be the most potent Abeta peptide-degrading enzyme in the brain.
      Decreasing the activity of NEP (due to genetic mutations, age or diseases that
      alter the expression or activity of NEP) may lead to accumulation of the
      neurotoxic Abeta peptide in the brain; in turn this leads to neuronal loss. We
      investigated the efficacy of lentivirus-mediated over-expression of NEP to
      protect neuronal cells from Abeta peptide in vitro. Incubation of hippocampal
      neuronal cells (HT22) over-expressing NEP with the monomeric from of Abeta
      peptide decreases the toxicity of Abeta peptide on the neuronal cells, as
      measured through cell viability. We conclude that over-expression of NEP by a
      gene therapy approach in areas vulnerable to Abeta peptide aggregation in AD
      brain may protect the neurons from the toxicity effects of Abeta peptide and this
      promises a great potential target for altering the development of AD.

PMID- 17459355
TI  - Pivotal role of cardiac lineage protein-1 (CLP-1) in transcriptional elongation
      factor P-TEFb complex formation in cardiac hypertrophy.
AB  - OBJECTIVE: Our aim was to determine if the expression pattern of CLP-1 in
      developing heart is consistent with its role in controlling RNA transcript
      elongation by transcriptional elongation factor b (P-TEFb) and if the inhibitory
      control exerted over P-TEFb by CLP-1 is released under hypertrophic conditions.
      METHODS: We performed immunoblot and immunofluorescence analysis of CLP-1 and the
      P-TEFb components cdk9 and cyclin T in fetal mouse heart and 2 day post-natal
      mouse cardiomyocytes to determine if they are co-localized. We induced
      hypertrophy in rat cardiomyocytes either by mechanical stretch or treatment with
      hypertrophic agents such as endothelin-1 and phenylephrine to determine if CLP-1
      is released from P-TEFb in response to hypertrophic stimuli. The involvement of
      the Jak/STAT signal transduction pathway in this process was studied by blocking
      this pathway with the Jak2 kinase inhibitor, AG490, and assessing the association
      of CLP-1 with P-TEFb complexes. RESULTS: We found that CLP-1 is expressed along
      with P-TEFb components in developing heart during the period in which knockout
      mice lacking the CLP-1 gene develop cardiac hypertrophy and die. Under conditions
      of hypertrophy induced by mechanical stretch or agonist treatment, CLP-1
      dissociates from the P-TEFb complex, a finding consistent with the de-repression
      of P-TEFb kinase activity seen in hypertrophic cardiomyocytes. Blockage of
      Jak/STAT signaling by AG490 prevented release of CLP-1 from P-TEFb despite the
      ongoing presence of hypertrophic stimulation by mechanical stretch. CONCLUSIONS:
      CLP-1 expression in developing heart and isolated post-natal cardiomyocytes
      colocalizes with P-TEFb expression and therefore has the potential to regulate
      RNA transcript elongation by controlling P-TEFb cdk9 kinase activity in heart. We
      further conclude that the dissociation of CLP-1 from P-TEFb is responsive to
      hypertrophic stimuli transduced by cellular signal transduction pathways. This
      process may be part of the genomic stress response resulting in increased RNA
      transcript synthesis in hypertrophic cardiomyocytes.

PMID- 17459356
TI  - Gap junctions in preconditioning against arrhythmias.

PMID- 17459357
TI  - Tenascin-C: a key molecule in graft stenosis.

PMID- 17459358
TI  - Overexpression of protein kinase C alpha mRNA in human hepatocellular carcinoma:
      a potential marker of disease prognosis.
AB  - BACKGROUND: Members of the protein kinase C (PKC) isoenzyme family play a central
      role in the tumorigenesis of several tissues. However, little is known about
      subtype specific intracellular expression of PKC in human hepatocellular
      carcinomas. METHODS: We investigated PKC isoforms mRNA expression in 42 HCC
      specimens using reverse transcription polymerase chain reaction analysis, and the
      correlation between PKC isoforms expression and clinicopathologic parameters.
      RESULTS: We found that PKCalpha, PKCdelta and PKCiota mRNA were significantly
      increased in HCCs as compared to the corresponding non-cancerous liver tissues.
      PKCalpha expression also significantly correlated with tumor size (P<0.05) and
      TNM stage (P<0.05), but PKCdelta and PKCiota did not. The log-rank analysis
      revealed that patients with higher PKCalpha mRNA expression in the HCC tissues
      had significantly shorter survival rate than patients with lower PKCalpha mRNA
      expression (P<0.01). CONCLUSIONS: Our results suggested that the PKCalpha may be
      a prognostic factor for the survival of patients with HCC.

PMID- 17459359
TI  - A Glu487Lys polymorphism in the gene for mitochondrial aldehyde dehydrogenase 2
      is associated with myocardial infarction in elderly Korean men.
AB  - BACKGROUND: A homozygous mutant (ALDH2*2/*2) of the gene for mitochondrial
      aldehyde dehydrogenase 2 (ALDH2) at codon 487 was reported to be associated with
      myocardial infarction (MI) among Japanese men. However, such an association has
      never been studied in a Korean population. METHOD: The subjects consisted of 122
      men (60-81 y) with MI recruited randomly from Yonsei University Medical Center,
      Korea. A total of 439 men (60-84 y) without MI were selected as controls from the
      Ansan Geriatric Study. ALDH2 genotypes were determined using the TaqMan
      fluorogenic 5' nuclease polymerase chain reaction assay. RESULTS: Genotypes
      carrying the mutant ALDH2 allele (ALDH2*1/*2 plus ALDH2*2/*2) were significantly
      more frequent in patients with MI than in the controls (42.6% vs. 30.5%,
      P=0.0163). Multiple logistic regression analysis revealed that ALDH2*1/*2 plus
      ALDH2*2/*2, together with abnormal high density lipoprotein cholesterol and
      elevated body mass index, was an independent risk factor for MI in elderly Korean
      men (odds ratio=1.976, 95% CI: 1.202-3.248). CONCLUSIONS: ALDH2 polymorphisms may
      play an important role in the pathogenesis of MI in elderly Korean men.

PMID- 17459360
TI  - Measurement of cystine in granulocytes using liquid chromatography-tandem mass
      spectrometry.
AB  - BACKGROUND: Cystinosis is a rare autosomal recessive disorder characterized by an
      accumulation of intralysosomal cystine due to a defect in cystine transport
      across the lysosomal membrane. This disorder can be treated specifically using
      high doses of cysteamine. Accurate measurement of intracellular cystine content
      is necessary for the diagnosis and monitoring of treatment with cysteamine. Here
      we describe a new method to measure intracellular cystine. It relies on a liquid
      chromatography-tandem mass spectrometry assay. We compare this novel method with
      the cystine-binding protein assay. METHOD: Cells were isolated and lysed in the
      presence of N-ethylmaleimide to avoid interference from cysteine. After
      deproteinization, addition of stable isotope d6 cystine and butylation, cystine
      was measured using an API 3000 MSMS. RESULTS: The cystine assay was linear to at
      least 50 micromol/L. Within-run and between-run coefficients of variation were
      2.9% and 5.7% respectively. CONCLUSION: It is possible to measure very low
      concentrations of intracellular cystine with liquid chromatography-tandem mass
      spectrometry. The results obtained with this novel method correlate very well
      with those obtained using the cystine-binding protein assay.

PMID- 17459361
TI  - Comparison of three methods for genotyping the UGT1A1 (TA)n repeat polymorphism.
AB  - OBJECTIVES: The UGT1A1 promoter contains a (TA)n repeat polymorphism. The 7
      repeat allele is associated with decreased enzyme activity and patients
      homozygous for this allele treated with irinotecan may experience life
      threatening toxicity. Here, we have compared three methods [DNA sequencing,
      fragment analysis, and the Invader assay (Third Wave Technologies)] for
      genotyping this polymorphism. RESULTS: All of the DNA samples (n=119) had
      concordant genotype calls between the sequencing and size-based methods. The
      Invader method was also concordant if the genotypes were 6/6, 6/7, or 7/7. Both
      the size-based method and the Invader method had straightforward data analysis,
      while interpretation of the sequencing results was occasionally more challenging.
      The Invader method required more concentrated DNA for analysis, was more
      expensive, and had a limited genotyping spectrum. CONCLUSION: All three methods
      were valuable for genotyping the UGT1A1 (TA)n repeat, with the sequencing and
      size-based assays having the fewest drawbacks.

PMID- 17459362
TI  - The cause of infant categorization?
AB  - We asked whether infants are sensitive to causal relations between objects and
      outcomes and whether this sensitivity supports categorization. Fourteen- and 18
      month-old infants were familiarized with objects from a novel category. For some,
      the objects caused an electronic toy to activate. For others, the objects were
      present during activation of the toy, but did not cause the event. For the
      remaining infants, the events were never activated. Infants were asked to select
      another category member from a pair of previously unseen objects (one from the
      familiar, and one from a novel, category). Infants were more likely to select the
      category match in the causal than the non-causal and no outcome conditions,
      suggesting that they capitalize on causal information in forming object
      categories.

PMID- 17459363
TI  - Egg water from the amphibian Bufo arenarum induces capacitation-like changes in
      homologous spermatozoa.
AB  - Mammalian sperm acquire fertilizing capacity after residing in the female tract,
      where physiological changes named capacitation take place. In animals with
      external fertilization as amphibians, gamete interactions are first established
      between sperm and molecules of the egg jelly coat released into the medium. Since
      dejellied oocytes are not normally fertilized, the aim of this study was to
      determine if the jelly coat of the toad Bufo arenarum promotes a "capacitating"
      activity on homologous sperm. We found that sperm incubation in diffusible
      substances of the jelly coat (egg water) for 90-180 s is sufficient to render
      sperm transiently capable of fertilizing dejellied oocytes. The fertilizing state
      was correlated with an increase of protein tyrosine phosphorylation and a
      decrease of sperm cholesterol content. Inhibition of either the increase in
      tyrosine phosphorylation or cholesterol efflux affected the acquisition of
      fertilizing capacity. Phosphorylation and fertilization could be promoted with
      NaHCO(3) and also by addition of beta cyclodextrin. Moreover, sperm could gain
      the ability to fertilize dejellied oocytes in the presence of these compounds.
      These data indicate that sperm should undergo a series of molecular changes to
      gain fertilizing capacity; these changes are reminiscent of mammalian sperm
      capacitation and take place before the acrosome reaction.

PMID- 17459364
TI  - Direct activation by Ets and Zic is required for initial expression of the
      Brachyury gene in the ascidian notochord.
AB  - Extrinsic fibroblast growth factor (FGF) signal and intrinsic factors that
      determine the response of the signal-receiving blastomeres to FGF regulate
      mesoderm patterning in embryos of the ascidian Halocynthia roretzi. To
      investigate how cells integrate information from extrinsic and intrinsic inputs,
      we examined Brachyury (Hr-Bra) promoter activity in the early embryo. Hr-Bra,
      which encodes a key transcription factor for notochord development, is expressed
      exclusively in notochord precursors in a manner dependent on the FGF-MEK-MAPK-Ets
      signaling pathway and on the intrinsic factors Zic and FoxA. Reporter gene
      expression driven by the 900-bp upstream region of the Hr-Bra promoter was
      detected as early as the 110-cell stage in notochord precursors by in situ
      hybridization with a LacZ probe. Deletion analysis combined with MEK inhibitor
      treatment demonstrated that the -598/-499 region carries FGF-responsiveness.
      Electrophoretic mobility shift assay identified three Ets-binding sites in this
      region that were required for promoter activity. Further deletion analysis
      conducted by injecting eggs with reporter constructs at higher concentration
      suggested that the -398/-289 region also has enhancer activity, although ectopic
      reporter expression was detected in nerve cord and endoderm precursors. The -398/
      289 region has a Zic-binding site that was also essential for the enhancer
      activity. These results indicate that Ets- and Zic-binding sites are critical for
      the initiation of Hr-Bra expression. In conclusion, information from both
      extrinsic and intrinsic factors is integrated at the level of enhancer of the
      target gene by direct binding of the transcription factors to the enhancer
      region.

PMID- 17459365
TI  - Fish consumption and advisory awareness among low-income women in California's
      Sacramento-San Joaquin Delta.
AB  - Fishing is a culturally important activity to the ethnically diverse population
      living in California's Sacramento-San Joaquin Delta. Due to runoff from abandoned
      gold mines, certain Delta fish are contaminated with methylmercury, a
      neurodevelopmental toxin. A state health advisory recommends limited consumption
      of certain Delta fish, to be followed in conjunction with a federal advisory for
      commercial and sport fish. We conducted a survey of low-income women at a Special
      Supplemental Nutrition Program for Women, Infants, and Children (WIC) clinic, to
      characterize commercial and sport fish consumption patterns and advisory
      awareness. Ninety-five percent of women consumed commercial fish. Thirty-two
      percent consumed sport fish; this proportion was much higher in Hmong (86%) and
      Cambodian (75%) women. Ninety-nine percent of sport fish consumers also consumed
      commercial fish. The overall fish consumption rate among consumers was 27.9 g/day
      (geometric mean, past 30 days, cooked portion); commercial and sport fish
      consumption rates were 26.3 and 10.5 g/day, respectively. We found ethnic
      differences in overall fish consumption rates, which were highest in African
      Americans (41.2 g/day) and Asians (35.6 g/day), particularly Vietnamese and
      Cambodians. Pregnant women ate less fish overall than other women (16.8 vs. 30.0
      g/day, p=0.0001), as did women who demonstrated specific advisory awareness (23.3
      vs. 30.3 g/day, p=0.02). Twenty-nine percent of all women exceeded federal fish
      consumption advisory limits. These results highlight the need for culturally and
      linguistically appropriate interventions that address both commercial and sport
      fish consumption.

PMID- 17459366
TI  - Seasonal variation of arsenic concentration in wells in Nevada.
AB  - The issue of seasonal arsenic measurement variability poses consequences
      regarding the interpretation and frequency of well water measurements for both
      public health research and surveillance. In this study, we evaluated seasonal
      variability in arsenic concentration in 356 wells in western Nevada. River flow
      data obtained from US Geological Survey National Water Information System were
      used to classify seasons as wet or dry, and mean differences in arsenic well
      concentrations measured during these seasons were compared. Arsenic
      concentrations in these wells averaged 72.9 microg/L (range, non-detect to 3000
      microg/L). The mean difference in arsenic concentrations between the wet and dry
      seasons was -3.3 microg/L (p = 0.78; average percent difference = 2.3%). Eighty
      wells (22%) had higher arsenic concentrations in the wet season, 75 wells (21%)
      had higher arsenic concentrations in the dry season and no difference was seen in
      201 wells (56%). The mean differences in wells with arsenic levels of 0-10, 11
      50, 51-200, > 200 microg/L were -1.4 microg/L(p=0.43), 9.2 microg/L(p=0.36), 15.1
      microg/L(p=0.30), and -49.9 microg/L(p=0.59). In summary, although changes in
      arsenic concentrations were seen in some wells, clear trends in arsenic
      concentration over time were not associated with the wet and dry seasons. These
      findings provide evidence that, in our study area as a whole, little seasonal
      variability occurs in arsenic concentrations, and repeated assessments of arsenic
      concentrations based on season might add little value to the accuracy of health
      effects research or public health surveillance.

PMID- 17459367
TI  - Development of new atopic dermatitis models characterized by not only itching but
      also inflammatory skin in mice.
AB  - The present study was performed to develop a new atopic dermatitis model
      characterized by not only itching but also inflammatory skin using BALB/c mice.
      From 18 days after the first systemic immunization, daily epicutaneous
      application of ovalbumin was performed for 2 weeks. Antigen challenge (ovalbumin)
      resulted in a significant increase of scratching behavior from day 23 to day 32.
      Moreover, skin symptoms such as erythema/hemorrhage, edema, excoriation/erosion
      and dryness/desquamation were also observed from day 19 to day 32. The frequency
      of scratching in the first stage (from day 24 to day 26 after the systemic first
      immunization) was decreased by chlorpheniramine and epinastine; however, in the
      last stage (from day 27 to day 30 after the systemic first immunization), both
      drugs showed no inhibition of scratching behavior. Therefore, an endogenous
      mediator other than histamine may be responsible for provoking the itching
      sensation in the last stage. Naloxone dose-dependently reduced the frequency of
      scratching in the last stage. Moreover, repeated local application of
      dexametasone significantly inhibited both scratching behavior and skin symptoms
      from day 24 to day 30. From these findings, it may be concluded that this model
      is essentially similar to atopic dermatitis in humans and could be used to
      elucidate the pathogenic mechanisms of atopic dermatitis and to develop
      appropriate new drugs for therapy.

PMID- 17459368
TI  - Platelet activation triggered by Chlamydia pneumoniae is antagonized by 12
      lipoxygenase inhibitors but not cyclooxygenase inhibitors.
AB  - Chlamydia pneumoniae is a respiratory pathogen that has been linked to
      cardiovascular disease. We have recently shown that C. pneumoniae activates
      platelets, leading to oxidation of low-density lipoproteins. The aim of the
      present study was to evaluate the inhibitory effects of different pharmacological
      agents on platelet aggregation and secretion induced by C. pneumoniae. Platelet
      interaction with C. pneumoniae was studied by analyzing platelet aggregation and
      ATP-secretion with Lumi-aggregometry. Platelet aggregation and ATP-secretion
      induced by C. pneumoniae was markedly inhibited by the NO-donor S-nitroso-N
      acetyl-D,L-penicillamine (SNAP), an effect that was counteracted by the guanylyl
      cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Pre
      treatment of platelets with the 12-lipoxygenase (12-LOX) inhibitors cinnamyl-3,4
      dihydroxy-alpha-cyanocinnamate (CDC) and 5,6,7-trikydroxyflavone (baicalein)
      completely blocked the activation, whereas the cyclooxygenase (COX) inhibitors 2
      acetyloxybenzoic acid (aspirin) and (8E)-8-[hydroxy-(pyridin-2
      ylamino)methylidene]-9-methyl-10,10-dioxo-10$l;(6)thia-9-azabicyclo[4.4.0]deca
      1,3,5-trien-7-one (piroxicam) had no inhibitory effects. Opposite to C.
      pneumoniae-induced activation, platelets stimulated by collagen were inhibited by
      the COX-inhibitors but were unaffected by the 12-LOX-inhibitors. The platelet
      activating factor (PAF) antagonist Ginkgolide B blocked the C. pneumoniae-induced
      platelet activation, whereas the responses to collagen were unaffected.
      Furthermore, the P2Y1 and P2Y12 purinergic receptor antagonists 2'-deoxy-N6
      methyladenosine 3',5'-bisphosphate (MRS2179) and N(6)-(2-methyl-thioethyl)-2
      (3,3,3-trifluoropropylthio)-beta,gamma-dichloromethylene-ATP (cangrelor)
      inhibited the aggregation and secretion caused by C. pneumoniae. It is well-known
      that the efficacy of COX inhibitors in the prevention and treatment of
      cardiovascular disease varies between different patients, and that patients with
      low responses to aspirin have a higher risk to encounter cardiovascular events.
      The findings in this study showing that platelets stimulated by C. pneumoniae are
      unaffected by COX inhibitors but sensitive to 12-LOX inhibitors, may thus be of
      importance in future management of atherosclerosis and thrombosis.

PMID- 17459369
TI  - NIH 11082 produces anti-depressant-like activity in the mouse tail-suspension
      test through a delta-opioid receptor mechanism of action.
AB  - The present study examined the effects of NIH 11082 ((-)-(1R,5R,9R)-5,9-dimethyl
      2'-hydroxy-2-(6-hydroxyhexyl)-6,7-benzomorphan hydrochloride), a benzomorphan
      analogue, in the mouse tail-suspension, an assay used to detect anti-depressant
      agents. NIH 11082 significantly decreased immobility time during tail-suspension,
      with a comparable magnitude as the tricyclic anti-depressant desipramine.
      Importantly, NIH 11082 failed to elicit convulsions or other overt behavioral
      signs of toxicity. The delta-opioid receptor antagonist naltrindole (AD50=2.0
      mg/kg), but not the non-selective mu-opioid receptor antagonist naltrexone or the
      kappa-opioid receptor antagonist nor-BNI, blocked the effects of NIH 11082 in the
      tail-suspension test. These results reinforce the notion that delta-opioid
      receptor agonists can produce significant effects in a behavioral model used to
      screen anti-depressant drugs.

PMID- 17459370
TI  - Role of cyclin-dependent kinase 5 in capsaicin-induced cough.
AB  - The role of cyclin-dependent kinase 5 (Cdk5) in the capsaicin-induced cough
      reflex was examined in mice. Pretreatment with inhaled roscovitine, a selective
      Cdk5 inhibitor, at concentrations of 0.3 to 3 mM inhibited the number of
      capsaicin-induced coughs in a concentration-dependent manner. Pretreatment with
      inhaled roscovitine, at a concentration of 3 mM also slightly but significantly
      inhibited the number of citric acid-induced coughs. The number of capsaicin
      induced coughs was significantly reduced when C-fibers were desensitized by the
      pretreatment with capsaicin. The number of citric acid-induced coughs was
      slightly but significantly reduced in capsaicin-pretreated mice as compared with
      that in naive mice. Although the inhalation of roscovitine at a concentration of
      3 mM significantly reduced the number of citric acid-induced coughs in naive mice
      to the level observed in capsaicin-pretreated mice, roscovitine had no effect on
      the number of citric acid-induced coughs in capsaicin-pretreated mice. These
      results suggest that Cdk5-dependent factors are involved in C-fiber-mediated
      cough signaling.

PMID- 17459371
TI  - 4-hydroxy nimesulide effects on mitochondria and HepG2 cells. A comparison with
      nimesulide.
AB  - We previously reported that the nonsteroidal anti-inflammatory drug, nimesulide
      (N-[4-nitro-2-phenoxyphenyl]-methanesulfonamide), is an uncoupler and oxidizes
      NAD(P)H in isolated rat liver mitochondria, triggering mitochondrial Ca2+ efflux
      or, if this effect is inhibited, eliciting mitochondrial permeability transition
      (Mingatto et al., Br. J. Pharmacol. 131:1154-1160, 2000). We presently
      demonstrated that nimesulide's hydroxylated metabolite (4-hydroxy nimesulide)
      lacks the uncoupling property of the parent drug, while keeping its ability to
      oxidize mitochondrial NADPH. In the presence of 10 microM Ca2+, low (5-50 microM)
      concentrations of 4-hydroxy nimesulide elicited mitochondrial permeability
      transition, as assessed by cyclosporin A-sensitive mitochondrial swelling,
      associated with mitochondrial Ca2+ efflux/membrane potential dissipation
      (Deltapsi), apparently occurring on account of the oxidation of mitochondrial
      protein thiols; no involvement of reactive oxygen species was observed. While
      nimesulide (0.5 or 1 mM, 30 h incubation) did not lead to significant HepG2 cell
      death, 4-hydroxy nimesulide caused a low extent (approximately 15%) of cell
      necrosis, partly prevented by cyclosporine A, suggesting the involvement of
      mitochondrial permeability transition. Both nimesulide and 4-hydroxy nimesulide
      caused NADPH oxidation and Deltapsi dissipation in HepG2 cells. Because such
      Deltapsi dissipation induced by the metabolite was almost completely inhibited by
      cyclosporine A, it probably results from the mitochondrial permeability
      transition. Therefore, mitochondrial permeability transition, in apparent
      association with NADPH oxidation, constitutes the most probable cause of HepG2
      cell death elicited by 4-hydroxy nimesulide.

PMID- 17459372
TI  - Acute effects of nicotine on restraint stress-induced anxiety-like behavior, c
      Fos expression, and corticosterone release in mice.
AB  - Clinical evidence suggests that nicotine reduces anxiety in stressful situations.
      In the present study, we investigated the effect of nicotine on restraint
      enhanced anxiety-like behavior, c-Fos expression, an index of neuronal activation
      in the brain, and plasma corticosterone. Two-hour restraint stress-enhanced
      anxiety-like behavior in the elevated plus-maze (EPM) and nicotine hydrogen
      tartrate (0.25 mg/kg, i.p.) attenuated the stress-induced changes. Pretreatment
      with the centrally acting nicotinic antagonist, mecamylamine (2 mg/kg), blocked
      nicotine's effects. In addition, restraint led to significant increases of c-Fos
      expression in several brain regions related to stress or anxiety including
      paraventricular hypothalamic nucleus (PVN), lateral hypothalamic area (LH),
      central amygdaloid nucleus (CeA), medial amygdaloid nucleus (MeA) and cingulate
      and retrosplenial cortices (Cg/RS), paraventricular thalamic nucleus (PVT), and
      basolateral amygdaloid nucleus (BLA). Nicotine attenuated the restraint-induced
      expression of c-Fos in the PVN, LH, CeA, MeA, and Cg/RS, while leaving the BLA
      and PVT unaffected. In contrast, nicotine did not reverse the increased levels of
      plasma corticosterone induced by restraint. These findings suggest that nicotine
      may modify the stress-induced behavioral changes via regulating the neuronal
      activation in selected brain regions rather than affecting hypothalamo-pituitary
      adrenocortical axis hormone responses.

PMID- 17459374
TI  - Vasodilatory mechanism of levobunolol on vascular smooth muscle cells.
AB  - Topical application of levobunolol hydrochloride, a beta-adrenergic antagonist
      used for treatment of glaucoma, is reported to increase ocular blood flow. We
      studied the mechanism of levobunolol-induced vasodilation in arterial smooth
      muscle. The effects of levobunolol or other agents on isolated, pre-contracted
      rabbit ciliary artery were investigated using an isometric tension recording
      method. The effects of the same agents on intracellular free calcium
      ([Ca(2+)](i)) in cultured human aortic smooth muscle cells were also studied by
      fluorophotometry. Levobunolol relaxed ciliary artery rings that were pre
      contracted with either high-K solution, 1microM histamine, 10microM
      phenylephrine, or 100nM endothelin-1. The relaxation induced by levobunolol was
      concentration-dependent over the range of 10microM to 0.3mM. Inhibition of
      endothelial nitric oxide synthase or denudation of the endothelium did not affect
      this relaxation. Histamine-induced contractions were inhibited by the histamine
      H(1) antagonist pyrilamine. Radioligand binding experiments showed that
      levobunolol did not bind to the H(1) receptor. Further, histamine induced
      transient contraction in Ca(2+)-free solution, and levobunolol inhibited this
      contraction by 74.6+/-11.0%. In cultured smooth muscle cells in the presence of
      extracellular Ca(2+), levobunolol significantly inhibited the histamine-induced
      elevation of [Ca(2+)](i). However, it did not inhibit the increase of [Ca(2+)](i)
      in histamine-stimulated cells incubated in Ca(2+)-free solution. These results
      indicate that levobunolol may relax rabbit ciliary artery by two different
      mechanisms. First, the relaxation could be due to the blockade of Ca(2+) entry
      through non-voltage-dependent Ca(2+) channels. Second, levobunolol may change the
      Ca(2+) sensitivity of vascular smooth muscle cells.

PMID- 17459373
TI  - Effects of imipramine on extracellular serotonin and noradrenaline concentrations
      in ACTH-treated rats.
AB  - We investigated the effect of imipramine on extracellular serotonin (5-HT) and
      noradrenaline concentrations in the medial prefrontal cortex of rats treated with
      adrenocorticotropic hormone (ACTH) for 14 days using in vivo microdialysis.
      Chronic ACTH treatment did not affect basal extracellular 5-HT and noradrenaline
      concentrations compared with chronic saline treatment. Acute imipramine treatment
      plus chronic ACTH treatment significantly increased extracellular 5-HT
      concentrations, compared with imipramine treatment alone. 8-hydroxy-2-di-n
      propylamino tetralin (8-OH-DPAT), a 5-HT1A receptors full agonist, caused a
      significant decrease in extracellular 5-HT concentrations. However, its
      inhibitory effect was attenuated by the treatment with ACTH for 14 days. These
      findings suggest that chronic treatment with ACTH enhances the increasing effect
      release of 5-HT by imipramine through the desensitization of somatodendritic 5
      HT1A autoreceptors.

PMID- 17459375
TI  - Introduction to awarding the von Sallmann prize to Eliot Berson.

PMID- 17459377
TI  - The human subventricular zone: a source of new cells and a potential source of
      brain tumors.
AB  - The mammalian brain has been perceived as a quiescent organ incapable of
      postnatal neurogenesis for many years. Most recently, several studies have
      demonstrated that the adult mammalian brain is indeed capable of neurogenesis and
      that the process is primarily confined to the subventricular zone (SVZ) of the
      forebrain and the subgranular zone (SGZ) of the hippocampus. Of these regions,
      the SVZ is the largest niche of neurogenesis in the adult mammalian brain. Within
      this niche resides a subpopulation of astrocytes with stem cell-like features of
      self-renewal and multipotentiality. Interestingly, there is also a subpopulation
      of cells within brain tumors that possess these same characteristics. Based on
      these findings, the emerging hypothesis is that brain tumor stem cells may be
      derived from neural stem cells and that both of these populations may originate
      from the SVZ. This possible connection stresses the importance of studying and
      understanding the role that the human SVZ plays in not only harboring neural and
      brain tumor stem cells, but how this microenvironment may support both
      neurogenesis and tumorigenesis. Furthermore, the obvious differences in the SVZ
      between humans and other animals make it important to understand the human model
      when studying human disease. Such an understanding may lead to novel therapeutic
      strategies for both neurodegenerative diseases and currently intractable brain
      tumors.

PMID- 17459376
TI  - The opioid receptor antagonist, naloxone, protects spinal motor neurons in a
      murine model of alphavirus encephalomyelitis.
AB  - Spread of neuroadapted Sindbis virus (NSV) to motor neurons (MN) of the spinal
      cord (SC) causes severe hind limb weakness in C57BL/6 mice and models the
      paralysis that can accompany alphavirus and flavivirus encephalomyelitis in
      humans. The fate of spinal MN dictates the severity of NSV-induced paralysis, and
      recent data suggest that MN damage can occur indirectly via the actions of
      activated microglial cells. Because the opioid receptor antagonist, naloxone
      (NAL), blocks microglial-mediated neurodegeneration in other models, we examined
      its effects during NSV infection. Drug treatment prevented paralysis and enhanced
      the survival of MN without altering NSV tropism, replication, or clearance from
      SC tissue. Further studies showed that NAL most effectively inhibited paralysis
      in a 72-h window after NSV challenge, suggesting that the drug inhibits an early
      event in SC pathogenesis. Histochemical studies demonstrated that NAL blocked
      early microglial activation in SC tissue sections, and protein assays showed that
      the early induction of pathogenic IL-1 beta was blunted in SC homogenates.
      Finally, loss of glutamate transporter-1 (GLT-1) expression in SC, an astrocyte
      glutamate reuptake protein responsible for lowering toxic extracellular levels of
      glutamate and preventing MN damage, was reversed by NAL treatment. This GLT-1
      loss proved to be highly IL-1 beta-dependent. Taken together, these data suggest
      that NAL is neuroprotective in the SC by inhibiting microglial activation that,
      in turn, maintains normal astrocyte glutamate homeostasis. We propose that drugs
      targeting such microglial responses may have therapeutic benefit in humans with
      related viral infections.

PMID- 17459378
TI  - Peri-sciatic administration of recombinant rat TNF-alpha induces mechanical
      allodynia via upregulation of TNF-alpha in dorsal root ganglia and in spinal
      dorsal horn: the role of NF-kappa B pathway.
AB  - Previous studies have shown that tumor necrosis factor-alpha (TNF-alpha) and TNF
      receptor 1 (TNFR1) in dorsal root ganglia (DRG) and in spinal dorsal horn are
      upregulated after nerve injury and that many TNF-alpha-containing neurons
      overexpress TNFR1. In the present study, we found that peri-sciatic
      administration of rat recombinant TNF-alpha (rrTNF) at the concentrations of 10,
      100 and 1000 pg/ml (daily for 2 days) induced mechanical allodynia in bilateral
      hindpaws, lasting for about 20 days. The immunoreactivity (IR) of TNF-alpha and
      TNFR1 in the ipsilateral (but not in the contralateral) L4 and L5 DRGs increased
      significantly on day 1 and day 3 after administration of rrTNF, respectively.
      Double immunofluorescence staining revealed that in DRGs the increased TNF-alpha
      IR was mainly in neuronal cells and with a lesser extent in satellite glial
      cells, while the upregulation of TNFR1-IR was almost restricted at neuronal
      cells. TNF-alpha-IR but not TNFR1-IR also increased in bilateral lumbar spinal
      dorsal horn from day 3 to day 14, which was observed in astrocytes, microglias
      and neurons. In addition, a progressive infiltration of monocyte/macrophages and
      T lymphocytes in the ipsilateral L5 DRG and sciatic nerve was observed, starting
      on day 2 following administration of rrTNF. Intrathecal delivery of PDTC (8.2 ng
      in 10 microl volume), a nuclear factor-kappa B (NF-kappaB) inhibitor, 30 min
      before each rrTNF administration blocked mechanical allodynia completely and
      inhibited the upregulation of TNF-alpha-IR and TNFR1-IR substantially. The
      results suggest that peri-sciatic administration of rrTNF may induce mechanical
      allodynia by an autocrine mechanism via activation of the NF-kappaB pathway.

PMID- 17459379
TI  - Plasmodium vivax: molecular cloning, expression and characterization of
      glutathione S-transferase.
AB  - Malaria parasite glutathione S-transferases (GSTs) are postulated to be essential
      for parasite survival by protecting the parasite against oxidative stress and
      buffering the detoxification of heme-binding compounds; therefore, GSTs are
      considered potential targets for drug development. In this study, we identified a
      Plasmodium vivax gene encoding GST (PvGST) and characterized the biochemical
      properties of the recombinant enzyme. The PvGST contained 618 bp that encoded 205
      amino acids and shared a significant degree of sequence identity with GSTs from
      other Plasmodium species. The recombinant homodimeric enzyme had an approximate
      molecular mass of 50kDa and exhibited GSH-conjugating and GSH-peroxidase
      activities towards various model substrates. The optimal pH for recombinant PvGST
      (rPvGST) activity was pH 8.0, and the enzyme was moderately unstable at 37
      degrees C. The K(m) values of rPvGST with respect to GSH and CDNB were 0.17+/
      0.09 and 2.1+/-0.4mM, respectively. The significant sequence homology and similar
      biochemical properties of PvGST and Plasmodium falciparum GST (PfGST) indicate
      that they may have similar molecular structures. This information may be useful
      for the design of specific inhibitors for plasmodial GSTs as potential
      antimalarial drugs.

PMID- 17459380
TI  - Isolation of potentially pathogenic strains of Acanthamoeba in wild squirrels
      from the Canary Islands and Morocco.
AB  - In this study, a survey was conducted in order to determine the presence and
      pathogenic potential of free-living amoebae of Acanthamoeba genus in a population
      of Barbary Ground squirrels in Fuerteventura Island (Canary Islands, Spain) and
      Morocco. Identification of Acanthamoeba was based on the morphology of cyst and
      trophozoite forms and PCR amplification with a genus specific primer pair. The
      pathogenic potential of Acanthamoeba isolates was characterized using PCRs with
      two primer pairs related to Acanthamoeba pathogenesis and cytotoxicity assays
      using human corneal cells. Isolates genotypes were also determined after
      ribosomal DNA sequencing. These data revealed that the potentially pathogenic
      isolates belonged to T3 and T4. To our knowledge, this is the first report
      presenting the isolation of potentially pathogenic Acanthamoeba strains in wild
      squirrels, and it is also the first description of the pathogenic T3 and T4
      Acanthamoeba genotypes in Fuerteventura and Morocco.

PMID- 17459381
TI  - The dioxin (aryl hydrocarbon) receptor as a model for adaptive responses of
      bHLH/PAS transcription factors.
AB  - This review examines the common theme of adaptive responses of bHLH/PAS proteins,
      using the dioxin receptor as a prototype. The bHLH/PAS family of transcriptional
      regulators are a group of key developmental and environmental stress sensing
      proteins. They employ a variety of post-translational control mechanisms to
      regulate their transcriptional output. Amongst this family, the dioxin receptor
      is best known for its ability to elicit toxic responses to dioxin and dioxin like
      chemicals even though it mediates more benign adaptive responses to non-toxic
      xenobiotics. We discuss what is known about dioxin receptor physiology, both
      adaptive and inherent, along with its molecular regulation and put this into the
      context of the wider bHLH/PAS family. We also raise the issue of its toxic
      responses, in particular the idea that it is the dysregulation of its poorly
      characterised housekeeping functions that leads to these outcomes.

PMID- 17459382
TI  - Na+ transport in plants.
AB  - The ability of plants to grow in high NaCl concentrations is associated with the
      ability of the plants to transport, compartmentalize, extrude, and mobilize Na(+)
      ions. While the influx and efflux at the roots establish the steady state rate of
      entry of Na(+) into the plant, the compartmentation of Na(+) into the cell
      vacuoles and the radial transport of Na(+) to the stele and its loading into the
      xylem establish the homeostatic control of Na(+) in the cytosol of the root
      cells. Removal of Na(+) from the transpirational stream, its distribution within
      the plant and its progressive accumulation in the leaf vacuoles, will determine
      the ability to deal with the toxic effects of Na(+). The aim of this review is to
      highlight and discuss the recent progress in understanding of Na(+) transport in
      plants.

PMID- 17459383
TI  - Interference of endocrine disrupting chemicals with aromatase CYP19 expression or
      activity, and consequences for reproduction of teleost fish.
AB  - Many natural and synthetic compounds present in the environment exert a number of
      adverse effects on the exposed organisms, leading to endocrine disruption, for
      which they were termed endocrine disrupting chemicals (EDCs). A decrease in
      reproduction success is one of the most well-documented signs of endocrine
      disruption in fish. Estrogens are steroid hormones involved in the control of
      important reproduction-related processes, including sexual differentiation,
      maturation and a variety of others. Careful spatial and temporal balance of
      estrogens in the body is crucial for proper functioning. At the final step of
      estrogen biosynthesis, cytochrome P450 aromatase, encoded by the cyp19 gene,
      converts androgens into estrogens. Modulation of aromatase CYP19 expression and
      function can dramatically alter the rate of estrogen production, disturbing the
      local and systemic levels of estrogens. In the present review, the current
      progress in CYP19 characterization in teleost fish is summarized and the
      potential of several classes of EDCs to interfere with CYP19 expression and
      activity is discussed. Two cyp19 genes are present in most teleosts, cyp19a and
      cyp19b, primarily expressed in the ovary and brain, respectively. Both aromatase
      CYP19 isoforms are involved in the sexual differentiation and regulation of the
      reproductive cycle and male reproductive behavior in diverse teleost species.
      Alteration of aromatase CYP19 expression and/or activity, be it upregulation or
      downregulation, may lead to diverse disturbances of the above mentioned
      processes. Prediction of multiple transcriptional regulatory elements in the
      promoters of teleost cyp19 genes suggests the possibility for several EDC classes
      to affect cyp19 expression on the transcriptional level. These sites include cAMP
      responsive elements, a steroidogenic factor 1/adrenal 4 binding protein site, an
      estrogen-responsive element (ERE), half-EREs, dioxin-responsive elements, and
      elements related to diverse other nuclear receptors (peroxisome proliferator
      activated receptor, retinoid X receptor, retinoic acid receptor). Certain
      compounds including phytoestrogens, xenoestrogens, fungicides and organotins may
      modulate aromatase CYP19 activity on the post-transcriptional level. As is shown
      in this review, diverse EDCs may affect the expression and/or activity of
      aromatase cyp19 genes through a variety of mechanisms, many of which need further
      characterization in order to improve the prediction of risks posed by a
      contaminated environment to teleost fish population.

PMID- 17459384
TI  - Real-time comparison of a number of predictive controllers.
AB  - Many model predictive control (MPC) algorithms have been proposed in the
      literature depending on the conditionality of the system matrix and the choice of
      its cost-function. This paper presents the newer MPC schemes such as extended
      predictive control (EPC) and shifted MPC as well as other well known forms. The
      control performance of these controllers are compared using two systems that are
      slow and fast reacting. The closed-loop responses are compared and the
      differences and similarities are explained on the basis of the structure of the
      control schemes. Disturbance rejection and the tracking of various setpoint
      trajectories are performed with good closed-loop results from all the
      controllers. It was found that the controllers that were specifically designed to
      reduce the system matrix ill-conditionality such as EPC and generalized
      predictive control provided better control performance when compared to other MPC
      methods.

PMID- 17459385
TI  - Positioning and tracking of a linear motion stage with friction compensation by
      fuzzy logic approach.
AB  - In this paper, the development of a fuzzy controller that compensates for
      nonlinear friction in a linear motion stage is presented. The experimental work
      and instrumentation set up is presented for this research. Based upon a nonlinear
      friction model, friction parameters were estimated from experimental results.
      Simulation and experimental validation on a ball-screw mechanism is presented,
      showing the effectiveness of the proposed controller. Furthermore, it is shown
      that the proposed fuzzy control scheme offers several implementation advantages
      such as smaller control effort, and reduced effect of measurement noise.
      Moreover, the fuzzy logic methodology displays superior performance when compared
      to a conventional PID controller. It also shows good and robust tracking with
      respect to system parameters variation.

PMID- 17459386
TI  - Women's perception of self-worth and access to health care.
AB  - OBJECTIVE: : Research has shown differences in health status and health care
      utilization related to culture, economic status, and health care development.
      This paper reports on a study comparing attitudes of women in three countries, at
      various stages of development, about their own health and self-worth and asks if
      these differences account for differences in health care utilization and
      inequities in health status. METHOD: : A questionnaire, administered to 100 women
      in each of Yemen, Uganda and Canada, explored women's perception of their own
      health and health care seeking behavior. RESULT: : Women's perception of
      themselves as worthy of care was positively related to utilization. The ability
      to make one's own health care decisions varied with her country's development
      level. Implementation strategies must consider women's decision-making capacity.
      CONCLUSION: : To achieve improved health status, policies and programs must
      commit to encouraging appropriate social and cultural changes, using a 'cross
      sectoral approach', involving both gender and development issues.

PMID- 17459387
TI  - Three-dimensional transrectal ultrasonography in adolescent patients with
      polycystic ovarian syndrome.
AB  - OBJECTIVES: To evaluate the diagnostic value of 3-dimensional transrectal
      ultrasonography (3D-TRS) in adolescent patients with polycystic ovarian syndrome
      (PCOS). METHODS: Ovarian follicle number, ovarian volume, ovarian stromal area,
      total ovarian area, and stromal area to total area ratio (S/A) were evaluated
      using 3D-TRS in 75 amenorrheic, oligomenorrheic, or asymptomatic virgin patients
      and 25 healthy controls. Serum biochemical markers of PCOS were assayed during
      the early follicular phase of the menstrual cycle in menstruating patients and
      controls, and on a randomly selected day in amenorrheic patients. RESULTS: When
      assessing the delicate structure of the ovary in virgin patients, 3D-TRS was
      convenient, accurate, specific, sensitive, and more reliable overall than
      transabdominal ultrasonography. Ovarian stromal area and S/A ratio were
      significantly greater in patients with PCOS than in controls, and also in the
      patients who had ultrasonically diagnosed polycystic ovaries without clinical or
      biochemical evidence of PCOS. The S/A ratio was the studied variable most
      significantly correlated with androgen levels. CONCLUSIONS: These findings
      indicated that, in adolescent patients, 3D-TRS combined with transabdominal
      ultrasonography can improve the precision of the diagnosis of PCOS. The S/A ratio
      may become the ultrasonographic diagnostic marker for PCOS.

PMID- 17459388
TI  - Three-dimensional ultrasound and three-dimensional power Doppler in the
      assessment of ovarian tumors.
AB  - OBJECTIVE: To determine preoperative method that predicts nature of ovarian
      tumors. METHODS: Fifty patients with complex pelvic masses assessed
      preoperatively with two-dimensional ultrasound (2DUS), two-dimensional power
      Doppler (2DPD), three-dimensional ultrasound (3DUS), three-dimensional power
      Doppler (3DPD), color Doppler. RESULTS: All patients underwent exploration, 19
      (38%) had benign tumors, 31 (62%) had ovarian cancer. 2DUS identified 29 cases
      suspicious for malignancy giving sensitivity, specificity, PPV and accuracy of
      80%, 78%, 86%, and 80%. 2DUS with 2DPD identified 28 suspicious cases giving
      sensitivity, specificity, PPV and accuracy of 80%, 84%, 89%, and 82%. 3DUS
      identified 31 suspicious cases including 28 cancers giving sensitivity,
      specificity, PPV and accuracy of 90%, 84%, 90%, and 88%. 3DUS with 3DPD,
      identified 34 suspicious cases including all 31 cancers giving sensitivity,
      specificity, PPV and accuracy of 100%, 84%, 91%, and 94%. Color Doppler RI of
      0.48 identified 28 cases of 31 cancers giving sensitivity of 90%. CONCLUSION:
      Evaluation by 3DUS with 3DPD improves diagnostic accuracy of ovarian tumors.

PMID- 17459389
TI  - Psychological factors in preterm labor and psychotherapeutic intervention.

PMID- 17459390
TI  - High prevalence of Fitz-Hugh-Curtis Syndrome in genital tuberculosis.

PMID- 17459391
TI  - Salivary hormones and parturition in healthy, primigravid women.

PMID- 17459392
TI  - Haptoglobin therapy during pregnancy for paroxysmal nocturnal hemoglobinuria with
      renal failure.

PMID- 17459393
TI  - Announcing the winner of the IJGO Prize Paper Award for 2006.

PMID- 17459394
TI  - Analysis of perfluorinated carboxylic acids in soils: detection and quantitation
      issues at low concentrations.
AB  - Methods were developed for the extraction from soil, identification, confirmation
      and quantitation by LC/MS/MS of trace levels of perfluorooctanoic acid (PFOA),
      perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA). Whereas PFOA,
      PFNA and PFDA all can be quantitated using the method of standard additions, PFOA
      also can be quantitated less laboriously using 13C4-PFOA as a matrix internal
      standard. The impact of extract matrices on signal varied between soils and
      temporally during analytical runs rendering 13C4-PFOA unsuitable as a matrix
      internal standard for quantitating perfluorinated carboxylic acids (PFCAs) other
      than PFOA, which co-elutes with 13C4-PFOA. In fact, for soil extracts,
      quantitation of PFCAs based on external calibrations proved about as accurate as
      use of matrix internal standards for target analytes that do not co-elute with
      the matrix internal standard. Also, 13C4-PFOA should be used carefully as a
      matrix internal standard for trace levels of PFOA because some 13C4-PFOA
      standards contain trace impurities of unlabelled PFOA. When the presence of PFCAs
      in soil extracts is being determined by LC/MS/MS, detection limits are best
      defined by statistical methods that quantify the significance of contrast between
      analytical signal and background noise using multiple analyses. Further, when
      developing a calibration of low concentrations using weighted regression, the
      central tendency of the calibration line is best fitted using graphical
      depictions of error. As the MDL for the transition-product quantitation ion is
      approached in LC/MS/MS, relatively weak signals of transition-product
      confirmation ions can be used as a rejection criterion by looking for anomalously
      high values of the ratio of the confirmation to the quantitation ion.

PMID- 17459395
TI  - Solid-phase extraction with C30 bonded silica for analysis of polycyclic aromatic
      hydrocarbons in airborne particulate matters by gas chromatography-mass
      spectrometry.
AB  - A solid-phase extraction (SPE) method using triacontyl bonded silica (C30) as
      sorbent was developed for the determination of 16 US Environmental Protection
      Agency polycyclic aromatic hydrocarbons (PAHs) in airborne particulate matters
      quantitatively by gas chromatography-mass spectrometry (GC-MS). Optimization
      experiments were conducted using spiked standard aqueous solution of PAHs and
      real airborne particulates samples aiming to obtain highest SPE recoveries and
      extraction efficiency. Factors were studied in SPE procedures including the
      concentration of organic modifier, flow rate of sample loading and elution
      solvents. The ultrasonication time and solvents were also investigated.
      Recoveries were in the range of 68-107% for standard PAHs aqueous solution and 61
      116% for real spiked sample. Limits of detection (LODs) and limits of
      quantification (LOQs) with standard solution were in the range of 0.0070-0.21
      microgL(-1) and 0.022-0.67 microgL(-1), respectively. The optimized method was
      successfully applied to the determination of 16 PAHs in real airborne particulate
      matters.

PMID- 17459396
TI  - Analysis of meat samples for anabolic steroids residues by liquid
      chromatography/tandem mass spectrometry.
AB  - A rapid, specific and highly sensitive multi-residue method for the determination
      of anabolic steroid residues in bovine, pork and poultry muscle tissues was
      developed. The sample preparation involves enzymatic digestion followed by
      extraction with methanol. The crude extract was cleaned up by solid-phase
      extraction (SPE) combining C18 and NH2 columns. The detection was carried out by
      a highly sensitive liquid chromatography/electrospray ionization tandem mass
      spectrometry (LC/ESI-MS/MS) method using both positive and negative ionization
      modes. Natural and synthetic steroids covering different polarities could be
      extracted, concentrated and purified using one single method. Mobile phase
      composition and additives were optimized to achieve the highest sensitivity. The
      linearity was not good enough for quantitative analysis but the method was well
      suited for qualitative confirmation. The method was validated according to the
      European Commission Decision 2002/657/EC. Decision limits (CCalpha) and detection
      capabilities (CCbeta) were below 0.5 ng g(-1) for all the compounds in the three
      types of meat studied. The developed method is suitable for routine analysis in
      our laboratories.

PMID- 17459397
TI  - Capillary electrochromatography of selected phenolic compounds of Chamomilla
      recutita.
AB  - This article explores the use of capillary electrochromatography for the analysis
      of chamomile (Chamomilla recutita L.) extracts. After a thorough study of
      analytical parameters such as mobile and stationary phase composition, applied
      voltage, and temperature, a methodology to determine 11 bioactive phenolic
      compounds (coumarins: herniarin, umbelliferone; phenylpropanoids: chlorogenic
      acid, caffeic acid; flavones: apigenin, apigenin-7-O-glucoside, luteolin,
      luteolin-7-O-glucoside; flavonols: quercetin, rutin and flavanone: naringenin) in
      chamomile extracts was proposed. The method was performed in a Hypersil SCX/C18
      column with pH 2.8 phosphate buffer at 50 mmol L(-1) containing 50% acetonitrile
      (pH adjusted before the addition of the organic solvent). All compounds were
      separated in less than 7.5 min under isocratic conditions. Figures of merit
      include linearity (peak area versus apigenin concentration) from 50.0-1000
      microg/mL (r2=0.995), and intra-day precision of retention time and peak area
      better than 1.3% CV and 15%, respectively. The limits of detection and
      quantification for apigenin were 35.0 microg/mL and 150.0 microg/mL,
      respectively. This article also describes an NMR 1H study, carried out to monitor
      a new clean-up procedure for extracts containing propyleneglycol, whose
      components are poorly retained in conventional octadecyl silica cartridges.

PMID- 17459398
TI  - Sample preparation for chromatography: an African perspective.
AB  - Africa as a continent has its unique challenges for analytical chemists in sample
      preparation for chromatographic analyses. The areas of agriculture, environment,
      food and health provide formidable challenges when it comes to method
      development, for example, drought can result in inadequate supplies of good
      quality water. The testing of water quality necessitates the development of assay
      methods that can be employed to not only determine the quantities of pesticides
      associated with malaria and tsetse fly eradication programmes, but also to
      monitor mycotoxins or neurotoxins. Urbanisation has also meant that endocrine
      disruptors such as phthalate esters need to be monitored. This review will
      profile some of the activities by analytical chemists practising in the African
      continent, who seek to address some of the challenges in sample preparation for
      chromatographic analyses.

PMID- 17459399
TI  - Two-dimensional capillary electrophoresis using tangentially connected
      capillaries.
AB  - A novel type of fused silica capillary system is described where channels with
      circular cross-sections are tangentially in contact with each other and connected
      through a small opening at the contact area. Since the channels are not crossing
      each other in the same plane, the capillaries can easily be filled with different
      solutions, i.e. different solutions will be in contact with each other at the
      contact point. The system has been used to perform different types of two
      dimensional separations and the complete system is fully automated where a high
      voltage switch is used to control the location of the high voltage in the system.
      Using two model compounds it is demonstrated that a type of two-dimensional
      separation can be performed using capillary zone electrophoresis at two different
      pH values. It is also shown that a compound with acid/base properties can be
      concentrated using a dynamic pH junction mechanism when transferred from the
      first separation to the second separation. In addition, the system has been used
      to perform a comprehensive two-dimensional capillary electrophoresis separation
      of tryptic digest of bovine serum albumin using capillary zone electrophoresis
      followed by micellar electrokinetic chromatography.

PMID- 17459400
TI  - Determination of isophorone in food samples by solid-phase microextraction
      coupled with gas chromatography-mass spectrometry.
AB  - A simple and sensitive method for the determination of isophorone in food samples
      was developed by headspace solid-phase microextraction (HS-SPME) coupled with gas
      chromatography-mass spectrometry (GC-MS). Isophorone was separated within 10 min
      by GC-MS using a DB-1 capillary column and detected with selective ion monitoring
      mode. The HS-SPME using a polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber
      provided effective sample enrichment, and was carried out by fiber exposition at
      60 degrees C for 45 min. The extracted isophorone was easily desorbed by fiber
      exposition in the injection port of a capillary GC-MS system, and carryover was
      not observed. Using this method, the calibration curve of isophorone was linear
      in the range 20-1000 pg/mL, with a correlation coefficient 0.9996 (n = 18), and
      the detection limit (S/N = 3) was 0.5 pg/mL. The HS-SPME/GC-MS method showed
      25,000-fold higher sensitivity than the direct injection method (1 microL
      injection). The within-day and between-day precisions (relative standard
      deviations) at the concentration of 1 ng/mL isophorone were 3.9% and 6.1% (n=5),
      respectively. This method was successfully applied to the analysis of food
      samples without interference peaks. The recoveries of isophorone spiked into food
      sample were above 84% for a 50 or 500 pg/mL spiking concentration. The analytical
      results of the contents of isophorone in various food samples were presented.

PMID- 17459401
TI  - Binding behavior of amino acid conjugates of indole-3-acetic acid to immobilized
      human serum albumin.
AB  - The affinity of indole-3-acetic acid (IAA), indole-3-propionic acid, indole-3
      butyric acid and 24 of their amino acid conjugates to immobilized human serum
      albumin, as expressed by the retention factor k (determined by HPLC), was
      dependent on (1) lipophilicity, (2) chirality and (3) functional groups in the
      amino acid moiety; in some cases conformation plays an additional role. Two
      lipophilicity-related parameters afforded quantitative correlations with k:
      retention on a C18 reversed-phase column (experimental approach) and the distance
      between the hydrophilic and hydrophobic poles of the molecules (in silico
      approach). Most compounds examined are possible metabolic precursors of IAA, an
      experimental tumor therapeutic.

PMID- 17459402
TI  - Determination of peptaibol trace amounts in marine sediments by liquid
      chromatography/electrospray ionization-ion trap-mass spectrometry.
AB  - Extraction followed by reverse phase liquid chromatography (LC)/electrospray
      ionization-ion trap-mass spectrometry (ESI-IT-MS) analysis has been successfully
      developed for the determination of peptaibols, fungal toxic metabolites, in
      marine sediments. Spiking experiments showed that the mean recovery of target
      compounds exceeded 85% at a spiking level of 10 ng/g of sediment (wet weight).
      Detection and quantification limits were 250 and 830 pg/g of sediment,
      respectively. The method developed constituted the first sensitive assay for
      quantification of peptaibol trace amounts in a natural environment. A
      concentration of 5 ng/g in sediment samples collected from Fier d'Ars was found.

PMID- 17459403
TI  - Complexation studies with lanthanides and humic acid analyzed by ultrafiltration
      and capillary electrophoresis-inductively coupled plasma mass spectrometry.
AB  - For the long-term storage of radioactive waste, detailed information about geo
      chemical behavior of radioactive and toxic metal ions under environmental
      conditions is necessary. Humic acid (HA) can play an important role in the
      immobilisation or mobilisation of metal ions due to complexation and colloid
      formation. Therefore, we investigate the complexation behavior of HA and its
      influence on the migration or retardation of selected lanthanides (europium and
      gadolinium as homologues of the actinides americium and curium). Two independent
      speciation techniques, ultrafiltration and capillary electrophoresis coupled with
      inductively coupled plasma mass spectrometry (CE-ICP-MS) have been compared for
      the study of Eu and Gd interaction with (purified Aldrich) HA. The degree of
      complexation of Eu and Gd in 25 mg l(-1) Aldrich HA solutions was determined with
      a broad range of metal loading (Eu and Gd total concentration between 10(-6) and
      10(-4) mol l(-1)), ionic strength of 10 mM (NaClO4) and different pH-values. From
      the CE-ICP-MS electropherograms, additional information on the charge of the Eu
      species was obtained by the use of 1-bromopropane as neutral marker. To detect HA
      in the ICP-MS and separate between HA complexed and non complexed metal ions in
      the CE-ICP-MS, we have halogenated the HA with iodine as ICP-MS marker.

PMID- 17459404
TI  - Electrostatic assembly and growth of gold nanoparticles in cellulosic fibres.
AB  - Synthetic studies of nanocomposites containing gold nanoparticles attached onto
      wood or bacterial cellulosic fibres have been performed in situ in the presence
      of the fibres or by polyelectrolyte-assisted deposition. The optical properties
      of the final nanocomposites could be tailored not only by the starting Au
      nanoparticles characteristics but also by the preparative method associated to
      the type of cellulosic fibres used as the substrate. Thus, gold nanoparticles
      assembled or generated in situ within cellulosic fibres, are excellent components
      for long term optical and chemically stable nanocomposites, which appear
      particularly interesting for security paper applications.

PMID- 17459405
TI  - Visceral leishmaniosis and parapoxvirus infection in a Mediterranean monk seal
      (Monachus monachus).
AB  - A Mediterranean monk seal was shown by immunohistochemical and polymerase chain
      reaction techniques to be dually infected with a Leishmania sp. and parapoxvirus.
      The pathological findings included a deep ulcer on the side of the head, ulcers
      on the gingival and inner aspect of the lower lip, enlarged lymph nodes and
      tonsils, and respiratory lesions (pulmonary consolidation, oedema, haemorrhages
      and emphysema; tracheal and bronchial congestion, exudates and haemorrhage).
      Amastigotes were demonstrated in macrophages in the lymph nodes and spleen, and
      intracytoplasmic inclusion bodies were observed in the tracheal and oral mucosa.

PMID- 17459406
TI  - An immunohistochemical assessment of the cutaneous immune response to louse
      infestation in cattle.
AB  - Skin samples were taken from 10 experimental cattle exposed naturally, during a
      period extending over two winters, to Bovicola bovis and Solenoptes capillatus,
      five becoming infested and five being protected from infestation by repeated
      treatment with ectoparasiticides. Skin sections were examined histopathologically
      and immunohistochemically for expression of the immune cell markers CD3, CD4, CD8
      and class II antigens of the major histocompatibility complex (MHC). Louse
      infested cattle had a mixed infiltration of the superficial dermis and
      perifollicular regions with eosinophils and mononuclear cells. The skin of
      infested cattle differed from that of non-infested cattle in showing
      significantly more cells expressing CD3, CD4 and MHC class II (P<0.05). Many of
      the MHC class II(+) cells had dendritic morphology, suggesting active antigen
      presentation within the lesions. Louse infestations have previously been thought
      to produce a type 1 hypersensitivity response, mediated by Th2 lymphocytes.
      However, the increased number of lymphocytes and antigen-presenting cells
      observed in the present study suggests that in chronic infestation there is
      activation of local cell-mediated (Th1) immunity.

PMID- 17459407
TI  - Canine necrotizing encephalitis associated with anti-glomerular basement membrane
      glomerulonephritis.
AB  - A 2-year-old male West Highland white terrier with a 4-month history of seizures
      was referred for investigation. Depressed mentation, proprioceptive deficit and
      decreased menace response were noted at neurological examination. Post-mortem
      examination of the brain revealed multifocal lesions located principally in the
      left side of the diencephalon and mesencephalon. The lesions consisted of non
      suppurative inflammation and large areas of cavitation. The clinical evaluation
      and histopathological findings were consistent with a diagnosis of necrotizing
      meningoencephalitis (NME). Immunofluorescence performed on frozen sections of
      kidney revealed strong smooth linear labelling of the glomerular basement
      membrane with anti-IgG serum as well as weaker linear labelling with anti-IgM
      serum. This histomorphological pattern was consistent with anti-glomerular
      basement membrane glomerulonephritis. The association of this type of
      glomerulonephritis with a necrotizing encephalitis would support the hypothesis
      of an immune-mediated aetiology for NME.

PMID- 17459408
TI  - Hepatic changes in congenital Schistosoma japonicum infections in pigs.
AB  - The inflammatory response in liver tissue from piglets congenitally infected with
      Schistosoma japonicum was examined at two different timepoints after infection.
      The piglets, which were the offspring of three sows infected with 9000 S.
      japonicum cercariae in the 10th week of gestation, were allocated into two groups
      (n=9 and 17) killed 5 or 11 weeks after birth, respectively. All piglets
      developed a low level infection,with no significant difference between the
      groups. Inflammatory lesions in the liver consisted mainly of granulomas in
      portal areas, often obliterating the portal veins, and frequently with central
      eggs or egg remnants. The granulomatous reaction consisted of epithelioid cells
      and occasional giant cells surrounded by layers of lymphocytes, eosinophils,
      plasma cells, and various amounts of collagen and fibroblasts. Mild to moderate
      infiltration of portal and septal connective tissue with eosinophils and
      lymphocytes was common, but the connective tissue was generally not increased. At
      the two timepoints, slight differences were observed in the numbers of
      eosinophils and lymphocytes in the granulomas and in the size of the
      granulomatous reaction. The same pattern of immunohistochemical labelling was
      seen in both groups. CD79alpha(+) B cells were scarce except in granuloma
      associated lymphoid follicles;the majority of lymphocytes in granulomas and at
      other sites were CD3epsilon(+) T cells. The granulomatous reaction in the livers
      of piglets to schistosoma eggs from prenatal S. japonicum infection was similar
      to that seen in postnatal infection. Signs of immunomodulation of granulomas
      between the two timepoints of infection were not demonstrable.

PMID- 17459409
TI  - Foot-and-mouth disease virus crosses the placenta and causes death in fetal
      lambs.
AB  - Eighteen pregnant sheep, six at 45 days gestation and twelve at 75 days
      gestation, were infected with foot-and-mouth disease virus (FMDV) type O UKG
      34/2001. Two sheep from each gestational group were killed at 2, 4, and 7 days
      post-inoculation (dpi). Three sheep, pregnant for 75 days at infection, were
      killed at 17 and 18 dpi. Real-time reverse-transcriptase polymerase chain
      reaction (RT-PCR) and virus isolation (VI) were used to detect viral RNA and
      infectious virus, respectively, in fetal tissues taken post mortem. Eleven
      fetuses were obtained from the six sheep inoculated at day 45 of gestation. Of
      these, two of three fetuses at 2 dpi had viral RNA detected by RT-PCR and virus
      was detected in one by VI. Viral RNA was detected in two of four fetuses at 4
      dpi, while viral RNA and virus were detected in all four fetuses at 7 dpi. No
      gross abnormalities were evident in these fetuses. In the group inoculated at day
      75 of gestation, viral RNA was detected in three of four fetuses at 4 dpi. Virus
      and viral RNA were detected in three of four fetuses at 7 dpi. Of the seven
      fetuses examined at 17 and 18 dpi, viral RNA was detected in five, and four of
      these had died in utero. Gross abnormalities including haemorrhage and oedema in
      a number of tissues were evident in many of the fetuses in this group, but no
      vesicular lesions were found. Viral RNA and virus were detected in the amniotic
      fluid associated with infected fetuses. This study is the first to demonstrate
      that FMDV may cause transplacental infection and fetal death.

PMID- 17459410
TI  - Characterization of sinoatrial node in four conduction system marker mice.
AB  - The specialized cardiac conduction system (CCS) consists of the sinoatrial node
      (SAN) and the atrioventricular (AV) conduction system (AVCS), which includes
      proximal (AV node, bundle of His and bundle branches) and distal (Purkinje
      fibers) components. In four CCS marker mice [two transgenic (cGATA6|lacZ,
      CCS|lacZ) and two targeted gene knock-in (minK|lacZ, Hop|lacZ)] the expression of
      the lacZ gene (beta-gal) has been reported to mark portions of the proximal and
      distal AVCS; the expression of this marker in the adult SAN is unknown. The
      primary objective of this study was to analyze the utility of these marker mice
      in the identification of the SAN. Intercaval and interventricular septal regions,
      containing all the components of the CCS, were freshly dissected from adult mice
      based on the anatomical landmarks and sectioned. Immunohistochemical
      characterization was performed with SAN markers (Cx45, HCN4), compared to the
      reporter expression (beta-gal) and markers of the working myocardium (Cx40 and
      Cx43). In all four of the CCS marker mice, we found that beta-gal expression is
      consistently observed in the proximal and distal AVCS. However, the presence of
      lacZ gene expression in the working myocardium outside the CCS and/or the absence
      of this reporter expression in the SAN prevent the effective use of these mice to
      identify the SAN, leading us to conclude that none of the four CCS marker mice we
      studied specifically mark the SAN.

PMID- 17459411
TI  - Exploration of pairing constraints identifies a 9 base-pair core within box C/D
      snoRNA-rRNA duplexes.
AB  - 2'-O-ribose methylation of eukaryotic ribosomal RNAs is guided by RNA duplexes
      consisting of rRNA and box C/D small nucleolar (sno)RNA sequences, the methylated
      sites invariably mapping five positions apart from the D box. Here we have
      analyzed the RNA duplex pairing constraints by investigating the features of 415
      duplexes from the fungus, plant and animal kingdoms, and the evolution of those
      duplexes within the 124 sets they group into. The D-box upstream 1st and >or=15th
      positions consist of Watson-Crick base-pairs, G:U base-pairs and mismatched bases
      with ratios close to random assortments; these positions display single base
      differences in >60% of the RNA duplex sets. The D-box upstream 2nd to 11th
      positions have >90% Watson-Crick base-pairs; they display single base mutations
      with a U-shaped distribution of lower values of 0% and 1.6% at the methylated
      site 5th and 4th positions, and double compensatory mutations leading to new
      Watson-Crick base-pairs with an inverted U-shaped distribution of higher values
      at the 8th to 11th positions. Half of the single mutations at the 3rd to 11th
      positions resulted in G:U base-pairing, mainly through A-->G mutations in the
      rRNA strands and C-->T mutations in the snoRNA strands. Double compensatory
      mutations at the 3rd to 11th positions are extremely frequent, representing 36%
      of all mutations; they frequently arose from an A-->G mutation in the rRNA
      strands followed by a T-->C mutation in the snoRNA strands. Differences in the
      mutational pathways through which the rRNA and snoRNA strand evolved must be
      related to differences in the rRNA and snoRNA copy number and gene organization.
      Altogether these data identify the D-box upstream 3rd to 11th positions as box
      C/D snoRNA-rRNA duplex cores. The impact of the pairing constraints on the
      evolution of the 9 base-pair RNA duplex cores is discussed.

PMID- 17459412
TI  - Distinct steps of cross-linking, self-association, and maturation of tropoelastin
      are necessary for elastic fiber formation.
AB  - Elastic fibers play an important role in the characteristic resilience of many
      tissues. The assembly of tropoelastin into a fibrillar matrix is a complex
      stepwise process and the deposition and cross-linking of tropoelastin are
      believed to be key steps of elastic fiber formation. However, the detailed
      mechanisms of elastic fiber assembly have not been defined yet. Here, we
      demonstrate the relationship between deposition and the cross-linking/maturation
      of tropoelastin. Our data show that a C-terminal half-fragment of tropoelastin
      encoded by exons 16-36 (BH) is deposited onto microfibrils, yet we detect very
      limited amounts of the cross-linking amino acid, desmosine, an indicator of
      maturation, whereas the N-terminal half-fragment encoded by exons 2-15 (FH) was
      deficient for both deposition and cross-linking, suggesting that elastic fiber
      formation requires full-length tropoelastin molecules. A series of experiments
      using mutant BH fragments, lacking either exon 16 or 30, or a deletion of both
      exons showed that self-association of tropoelastin polypeptides was an early step
      in elastic fiber assembly. Immunofluorescence and Western blot assay showed that
      the treatment of cell culture medium or conditioned medium with beta
      aminopropionitrile to inhibit cross-linking, prevented both the deposition and
      polymerization of tropoelastin. In conclusion, our present results support the
      view that self-association and oxidation by lysyl oxidase precedes tropoelastin
      deposition onto microfibrils and the entire molecule of tropoelastin is required
      for this following maturation process.

PMID- 17459413
TI  - Regeneration and repair in multiple sclerosis: the view of experimental
      pathology.
AB  - In order to devise a strategy to enhance remyelination in multiple sclerosis (MS)
      it is necessary to understand the cause of remyelination failure in MS. A case is
      made that areas of chronic demyelination arise because of concurrent loss of
      oligodendrocyte progenitor cells (OPCs) and oligodendrocytes and that because of
      the slow rate of repopulation that occurs in old individuals the recruited OPCs
      are not exposed to the acute inflammatory environment required to generate
      remyelinating oligodendrocytes. Based on this analysis the case is made that only
      areas of acute demyelination will be amenable to transplant-mediated
      remyelination. An analysis of the many cells that could be used to provide a
      source of remyelinating cells would indicate that structural repair of the CNS in
      MS would likely only be possible if neural precursors were used and the most
      promising route for their introduction would appear to be by intraventricular
      injection. Both neural precursors and mesenchymal stromal cells can be
      immunomodulatory and neuroprotective following intravenous injection; however,
      only neural precursors are likely to be able to contribute to structural repair
      of the damaged nervous system.

PMID- 17459414
TI  - Neuronal mdr-1 gene expression after experimental focal hypoxia: a new obstacle
      for neuroprotection?
AB  - Neuronal damage after stroke-associated brain hypoxia is a leading cause of long
      term disability and death. The refractoriness to therapeutic strategies for
      neuroprotection after 3 h post brain ischemia is poorly understood. P
      glycoprotein (P-gp), the multidrug resistance gene (MDR-1) product is normally
      expressed at blood-brain-barrier. P-gp neuronal expression has been demonstrated
      in refractory epilepsy and after brain ischemia. In this report we investigated
      the hypoxia-induced neuronal P-gp expression after local injection of CoCl(2) (1
      200 mM) in the fronto-parietal cortex of male adult rats (Bregma -1.30 mm) by
      stereotaxic surgery. P-gp immunostaining of brain slides was analyzed using
      specific monoclonal antibodies and double immunolabeling was done with specific
      astrocytic and neuronal markers. Five days after injection of 1 mM CoCl(2), P-gp
      expression surrounding the lesion site was observed in neurons, astrocytic end
      foot on capillary blood vessels and endothelial cells on blood vessels. Higher
      CoCl(2) doses (200 mM) resulted in additional P-gp immunostaining of the entire
      astrocytic and neuronal cytoplasm. Electron microscopy (EM) studies showed
      alterations in neurons as early as 6 h after the CoCl(2) injection. P-gp
      expression in hypoxic neurons and astrocytic end-foot could potentially impair of
      drugs access to the brain parenchyma thus suggesting the presence of two P-gp
      based pumping systems (one in astrocytes and other in the hypoxic neurons) that
      are able to behave as a previously unnoticed obstacle for pharmacological
      strategies of neuroprotection.

PMID- 17459415
TI  - Neurotrophic cross-talk between the nervous and immune systems: relevance for
      repair strategies in multiple sclerosis?
AB  - Autoreactive T and B cells are regular components of the healthy immune system.
      It has been proposed that some of these cells might have a protective function.
      Recent studies support this notion by demonstrating that a) myelin-autoreactive T
      cells show neuroprotective effects in vivo, and b) activated antigen-specific
      human T cells and other immune cells produce bioactive brain-derived neurotrophic
      factor (BDNF) and other neurotrophic factors in vitro. Furthermore, neurotrophic
      factors are expressed in different types of inflammatory cells in brain lesions
      of patients with acute disseminated leukoencephalopathy or multiple sclerosis. It
      seems plausible that the immune cell-mediated import of neurotrophic factors into
      the central nervous system has functional consequences, with obvious implications
      for the therapy of multiple sclerosis and other neuroimmunological diseases.

PMID- 17459416
TI  - Diagnostic markers for diagnosing dementia with Lewy bodies: CSF and MIBG cardiac
      scintigraphy study.
AB  - OBJECTIVE: This study examined the diagnostic value of cerebrospinal fluid (CSF)
      markers and iodine-123 metaiodobenzylguanidine ((123)I-MIBG) cardiac scintigraphy
      in distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease (AD).
      METHODS: CSF levels of amyloid beta1-42 (Abeta42) and 181-Thr phosphorylated tau
      (p-tau) were measured using enzyme linked immunosorbent assay (ELISA) kits.
      (123)I-MIBG cardiac scintigraphy was performed in patients with AD and DLB, and
      control (CTL) subjects. RESULTS: Increased CSF levels of p-tau in AD were found
      compared to DLB patients and CTL subjects (P<0.01), but there was no significant
      difference in CSF levels of Abeta42 between AD and DLB patients. The early and
      delayed heart to mediastinum (H/M) ratios of (123)I-MIBG cardiac scintigraphy
      were significantly decreased in patients with DLB compared to AD patients and CTL
      subjects (P<0.01). The receiver operating characteristic (ROC) analysis revealed
      that the diagnostic value of (123)I-MIBG cardiac scintigraphy was superior to
      that of CSF markers. CONCLUSIONS: (123)I-MIBG cardiac scintigraphy may be useful
      for discriminating between DLB and AD.

PMID- 17459417
TI  - Axonal and astrocyte injury markers in the cerebrospinal fluid of Kenyan children
      with severe malaria.
AB  - A retrospective study of cerebrospinal fluid (CSF) levels of markers of brain
      parenchymal damage was conducted in Kenyan children with severe falciparum
      malaria. Two markers were analysed by immunoassays: the microtubule-associated
      protein tau for degenerated axons and S-100B for astrocytes. The level of tau
      proteins in the CSF was significantly elevated in children with cerebral malaria
      compared with either malaria with prostration or malaria with seizures but normal
      consciousness (p<0.001). Elevated tau was also found to be associated with
      impaired delivery of oxygen (severe anaemia), severe metabolic acidosis
      manifesting as respiratory distress (increased respiratory rate and deep acidotic
      breathing) and at higher parasite densities. Elevated S-100B in children was
      associated with an increased risk of repeated seizures. This study provides
      evidence that axonal injury is associated with malaria coma and identifies the
      potential role of severe anaemia, acidosis and hyperparasitaemia to causing brain
      parenchymal damage in children with malaria.

PMID- 17459418
TI  - Acute intermittent porphyria with peripheral neuropathy: a follow-up study after
      hematin treatment.
AB  - We report a patient with acute intermittent porphyria who presented with
      progressive motor neuropathy, particularly in the upper limbs. The
      electrophysiological studies showed an asymmetric motor neuropathy with a
      prominent involvement of both the radial and left peroneal nerves. During the 1
      year follow-up period, 6 courses of hematin infusion, with 150 mg daily for 4
      consecutive days every month, were administrated. The motor neuropathy showed a
      steady and gradual improvement following the hematin treatment. Molecular
      analysis of the porphobilinogen deaminase gene revealed a short segment deletion
      (1008-1019delCAGCCTGGCCAA) resulting in a truncated protein. The findings suggest
      that early hematin treatment is temporally associated with interval improvement
      of the patient's porphyric motor neuropathy.

PMID- 17459419
TI  - A simple molecular mathematical model of mammalian hibernation.
AB  - A simple model of the dynamics of the body temperature of a hibernating mammal is
      presented. Our model provides a good match to experimental data, showing the
      interruption of low-temperature torpor bouts with periodic interbout arousals
      (IBAs). In this paper we present a mathematical model of the molecules that
      participate in the initiation, regulation, and maintenance of the hibernating
      state. This model can be used to describe the role of regulatory molecules,
      signal transducers, downstream target enzymes, structural proteins, or
      metabolites. Because many of the biochemical mechanisms are unknown, this is a
      preliminary and largely phenomenological model that we hope will inspire further
      investigation.

PMID- 17459420
TI  - Nitrosamines as nicotinic receptor ligands.
AB  - Nitrosamines are carcinogens formed in the mammalian organism from amine
      precursors contained in food, beverages, cosmetics and drugs. The potent
      carcinogen, NNK, and the weaker carcinogen, NNN, are nitrosamines formed from
      nicotine. Metabolites of the nitrosamines react with DNA to form adducts
      responsible for genotoxic effects. We have identified NNK as a high affinity
      agonist for the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) whereas NNN
      bound with high affinity to epibatidine-sensitive nAChRs. Diethylnitrosamine
      (DEN) bound to both receptors but with lower affinity. High levels of the
      alpha7nAChR were expressed in human small cell lung cancer (SCLC) cell lines and
      in hamster pulmonary neuroendocrine cells (PNECs), which serve as a model for the
      cell of origin of human SCLC. Exposure of SCLC or PNECs to NNK or nicotine
      increased expression of the alpha7nAChR and caused influx of Ca(2+), activation
      of PKC, Raf-1, ERK1/2, and c-myc, resulting in the stimulation of cell
      proliferation. Signaling via the alpha7nAChR was enhanced when cells were
      maintained in an environment of 10-15% CO(2) similar to that in the diseased
      lung. Hamsters with hyperoxia-induced pulmonary fibrosis developed neuroendocrine
      lung carcinomas similar to human SCLC when treated with NNK, DEN, or nicotine.
      The development of the NNK-induced tumors was prevented by green tea or
      theophylline. The beta-adrenergic receptor agonist, isoproterenol or theophylline
      blocked NNK-induced cell proliferation in vitro. NNK and nicotine-induced
      hyperactivity of the alpha7nAChR/RAF/ERK1/2 pathway thus appears to play a
      crucial role in the development of SCLC in smokers and could be targeted for
      cancer prevention.

PMID- 17459421
TI  - Expression and possible functions of the cholinergic system in a murine embryonic
      stem cell line.
AB  - The expression of a cholinergic system during embryonic development is a
      widespread phenomenon. However, no precise function could be assigned to it
      during early pre-neural stages and there are only few studies that document when
      it precisely starts to be expressed. Here, we examined the expression of
      cholinergic components in a murine embryonic stem cell line by RT-PCR,
      histochemistry, and enzyme activity measurements; the acetylcholine (ACh) content
      was measured by HPLC. We have demonstrated that embryonic stem cells express ACh,
      acetylcholine receptors, choline acetyltransferase (ChAT), acetyl- and butyryl
      cholinesterase (AChE and BChE). Butyryl-cholinesterase (BChE) expression was
      higher than AChE. The cholinesterase activity was down-regulated by adding
      specific inhibitors to culture medium. Inhibition of BChE led to a reduction of
      proliferation. This is the first demonstration that mouse embryonic stem cells
      express the full molecular equipment of a cholinergic system. Locally produced
      ACh might function as an intercellular signal, modulating the proliferation of
      stem cells.

PMID- 17459422
TI  - SP600125, a selective JNK inhibitor, protects ischemic renal injury via
      suppressing the extrinsic pathways of apoptosis.
AB  - Accumulating evidence suggests that c-Jun N-terminal kinase (JNK) signaling
      pathway plays a critical role in renal ischemia/reperfusion injury. However, the
      downstream mechanism that accounts for the proapoptotic actions of JNK during
      renal ischemia/reperfusion has not been elucidated. We report that SP600125, a
      potent, cell-permeable, selective, and reversible inhibitor of c-Jun N-terminal
      kinase (JNK), potently decreased renal epithelial tubular cell apoptosis induced
      by renal ischemia/reperfusion via suppression of the extrinsic pathway. This
      corresponds to the decrease in JNK phosphorylation at 20 min and c-Jun
      phosphorylation (Ser63/73) at 3 h after renal ischemia. Additionally, SP600125
      attenuated the increased expression of FasL induced by ischemia/reperfusion at 3
      h. The administration of SP600125 prior to ischemia was also protective. Thus,
      our findings imply that SP600125 can inhibit the activation of the JNK-c-Jun-FasL
      pathway and protect renal tubular epithelial cells against ischemia/reperfusion
      induced apoptosis. Taken together, these results indicate that targeting the JNK
      pathway provides a promising therapeutic approach for renal ischemia/reperfusion
      injury.

PMID- 17459423
TI  - Metallothionein in intestine of red mullet, Mullus barbatus as a biomarker of
      copper exposure in the coastal marine areas.
AB  - Dietary metal exposure in fish is studied in native red mullet, Mullus barbatus,
      involving metallothionein (MT) response in the intestine, a primary site for
      metal uptake. Intestinal MTs (microg mg(-1) proteins), total proteins (mgml(-1)
      S50), Cu, Zn, Fe, Mn and Cd (microg ml(-1) S50) are considered as indicators of
      metal exposure in specimens from near-shore and off-shore locations of the
      Eastern Adriatic Sea. Metallothionein and Cu are statistically significantly
      higher in 68 specimens from the Kastela Bay, a near-shore area (30.0+/-6.71microg
      MT mg(-1) proteins; 0.30+/-0.08microg Cu ml(-1) S50), in comparison to 51
      specimens from off-shore area, Solta Island (25.9+/-4.21microg MT mg(-1)
      proteins; 0.26+/-0.09microg Cu ml(-1) S50). Cytosolic Cu, a MT inducer, is
      significantly correlated (p<0.05, r=0.44) with MT in specimens from the Kastela
      Bay, independent on fish biometry. Our study indicates that cytosolic intestinal
      Cu and MT represent a measurable biochemical response in red mullet specimens,
      dwelling above sediments contaminated with Cu.

PMID- 17459424
TI  - Effects of L-arginine on cerebral blood flow, microvascular permeability, number
      of perfused capillaries, and brain water content in the traumatized mouse brain.
AB  - It is has been suggested that decreased production of the vasodilatory and anti
      aggregative substance NO (nitric oxide) may result in lower cerebral blood flow
      (CBF) in injured areas of the traumatized brain. The NO-precursor L-arginine has
      been shown to counteract CBF decreases early after trauma, but microcirculatory
      and more long-term effects on CBF of L-arginine have not been investigated. In an
      attempt to analyze effects of L-arginine on the microcirculation in the
      traumatized brain, the present study was designed to evaluate the effects of L
      arginine compared to vehicle (0.9% saline) following a standardized controlled
      cortical-impact brain trauma in mice. Cerebral blood flow (autoradiography
      [(14)C]-iodoantipyrine), number of perfused capillaries (FITC-dextran
      fluorescence technique), brain water content (wet vs. dry weight) and the blood
      to brain transfer constant K(i) for [(51)Cr]-EDTA were analyzed in the injured
      and the contralateral cortex. Cortical blood flow in the injured cortex was
      0.43+/-0.3 mL/g/min and 0.81+/-0.3 mL/g/min 3 h after trauma in the vehicle and L
      arginine groups, respectively (p<0.05), and no treatment effect was seen 24 h
      after trauma. The number of perfused capillaries decreased following trauma and
      was unaffected by L-arginine. K(i) increased following trauma and was unaffected
      by L-arginine. Brain water content was lower in the L-arginine group than in the
      vehicle group 3 h after trauma and there was no difference between the groups 24
      h after trauma. We conclude that L-arginine reduces brain edema formation and
      improves cortical blood flow in the early phase after a brain trauma, whereas no
      circulatory effects can be seen after prolonged treatment.

PMID- 17459425
TI  - A role for inflammatory mediators in the IL-18 mediated attenuation of LTP in the
      rat dentate gyrus.
AB  - Pro-inflammatory cytokines are known to be elevated in several pathological
      conditions that are associated with deficits in cognition. We have previously
      demonstrated that interleukin-18 (IL-18) inhibits long-term potentiation (LTP) in
      the dentate gyrus in vitro. In this study we have examined the involvement of the
      inflammatory mediators COX-2 and iNOS in IL-18-mediated inhibition of LTP. The
      effect of an anti-inflammatory PPARgamma agonist was also investigated. We report
      that the impairment of LTP by IL-18 is significantly attenuated by prior
      application of the COX-2 inhibitor, SC-236 and the iNOS inhibitor 1400W. These
      agents had no effect on paired pulse depression in the dentate gyrus.
      Furthermore, application of the PPARgamma agonist ciglitazone also attenuated IL
      18-mediated inhibition of LTP. We discuss a role for p38 MAP kinase in these
      effects. This study provides novel evidence for the involvement of inflammatory
      mediators in IL-18-mediated inhibition of LTP in the rat dentate gyrus in vitro.

PMID- 17459426
TI  - Voltammetric characterization of the effect of monoamine uptake inhibitors and
      releasers on dopamine and serotonin uptake in mouse caudate-putamen and
      substantia nigra slices.
AB  - Fast scan cyclic voltammetry is an electrochemical technique used to measure
      dynamics of transporter-mediated monoamine uptake in real time and provides a
      tool to evaluate the detailed effects of monoamine uptake inhibitors and
      releasers on dopamine and serotonin transporter function. We measured the effects
      of cocaine, methylphenidate, 2beta-propanoyl-3beta-(4tolyl) tropane (PTT),
      fluoxetine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine
      (MDMA), phentermine and fenfluramine on dopamine and serotonin uptake following
      electrically stimulated release in mouse caudate-putamen and substantia nigra
      pars reticulata slices. We determined rank orders of uptake inhibition effects
      based on two variables; increases in apparent K(m) for dopamine and serotonin
      uptake and inhibition constant (K(i)) values. For example, the rank order of
      uptake inhibition based on apparent K(m) values at the dopamine transporter was
      amphetamine>or=PTT>or=methylphenidate>>methamphetamine=phentermine=MDMA>cocaine>>
      luoxetine=fenfluramine, and at the serotonin transporter was
      fluoxetine=methamphetamine=fenfluramine=MDMA >
      amphetamine=cocaine=PTT>or=methylphenidate>phentermine. Additionally, changes in
      electrically stimulated release were documented. This is the first study using
      voltammetry to measure the effects of a wide range of monoamine uptake inhibitors
      and releasers on dopamine and serotonin uptake in mouse brain slices. These
      studies also highlight methodological considerations for comparison of effects
      between heterogeneous brain regions.

PMID- 17459427
TI  - Identification of residues mediating inhibition of glycine receptors by protons.
AB  - We previously identified H109 of the glycine alpha1 subunit as a putative proton
      binding site. In the present studies, we explored additional proton binding
      site(s) as well as the mechanism underlying modulation of glycine receptors by
      protons. Whole-cell glycine currents were recorded from HEK 293 cells transiently
      expressing wild type or mutant glycine receptors. Individual mutation of 3 of 4
      remaining extracellular histidine residue into alanine (i.e., alpha1 H107A, H215A
      or H419A), reduced the receptor sensitivity to protons to a varying extent. In
      contrast, mutation of alpha1 H201A did not affect proton sensitivity. Double,
      triple or quadruple histidine mutation of these residues caused a further
      reduction of proton sensitivity, suggesting multiple binding sites for proton
      action on glycine receptors. Furthermore, the substitution T133A, which mediates
      Zn(2+) inhibition, virtually abolished the proton effect on peak amplitude and
      current kinetics of glycine response. Replacement of T with S on position 133
      partially restored receptor sensitivity to protons, suggesting the hydroxyl group
      of residue T133 is essential for proton-mediated modulation. In heteromeric
      alpha1beta receptors, mutations beta H132A and S156A, which correspond to H109
      and T133 of the alpha1 subunit, respectively, also affected proton inhibition. In
      conclusion, multiple extracellular histidine residues (H107, H109, H215 and H419)
      and threonine residues of the alpha1 and beta Zn(2+) coordination sites are
      critical for modulation of the glycine receptor by protons.

PMID- 17459428
TI  - Orienting to social stimuli differentiates social cognitive impairment in autism
      and schizophrenia.
AB  - Both autism and schizophrenia feature deficits in aspects of social cognition
      that may be related to amygdala dysfunction, but it is unclear whether these are
      similar or different patterns of impairment. We compared the visual scanning
      patterns and emotion judgments of individuals with autism, individuals with
      schizophrenia and controls on a task well characterized with respect to amygdala
      functioning. On this task, eye movements of participants are recorded as they
      assess emotional content within a series of complex social scenes where faces are
      either included or digitally erased. Results indicated marked abnormalities in
      visual scanning for both disorders. Controls increased their gaze on face regions
      when faces were present to a significantly greater degree than both the autism or
      schizophrenia groups. While the control and the schizophrenia groups oriented to
      face regions faster when faces were present compared to when they were absent,
      the autism group oriented at the same rate in both conditions. The schizophrenia
      group, meanwhile, exhibited a delay in orienting to face regions across both
      conditions, although whether anti-psychotic medication contributed to this effect
      is unclear. These findings suggest that while processing emotional information in
      social scenes, both individuals with autism and individuals with schizophrenia
      fixate faces less than controls, although only those with autism fail to orient
      to faces more rapidly based on the presence of facial information. Autism and
      schizophrenia may therefore share an abnormality in utilizing facial information
      for assessing emotional content in social scenes, but differ in the ability to
      seek out socially relevant cues from complex stimuli. Impairments in social
      orienting are discussed within the context of evidence suggesting the role of the
      amygdala in orienting to emotionally meaningful information.

PMID- 17459429
TI  - Overweight children habituate slower than non-overweight children to food.
AB  - We have shown that physiological and behavioral responses habituate to food
      stimuli and recover when novel stimuli are presented. In addition, physiological
      responses in obese adults habituate slower to repeated food stimuli than those in
      non-obese individuals, which is related to greater energy intake. The purpose of
      this study was to test the hypothesis that instrumental responding in overweight
      children habituates slower to food cues than in their non-overweight peers.
      Children were provided the opportunity to work for access to cheeseburger for 10
      2-min trials, followed by French fries for 3 2-min trials. Results showed that
      children who had a body mass index (BMI) at or above the 85th BMI percentile (at
      risk for overweight; n=17) habituated slower than those with a BMI percentile
      less than the 85th BMI percentile (non-overweight; n=17). Response recovery to
      French fries did not differ between groups. Overweight children consumed
      significantly more grams of food and more energy than non-overweight children.
      When taken together, these data show that habituation may be an important
      individual difference characteristic that differentiates overweight from non
      overweight children. Implications of this for prevention and treatment of obesity
      are discussed.

PMID- 17459430
TI  - The palatability of corn oil and linoleic acid to mice as measured by short-term
      two-bottle choice and licking tests.
AB  - Free fatty acids (FFAs) were reported to be recognized in the oral cavity and
      possibly involved in fatty foods recognition. To understand the importance of oil
      recognition in the oral cavity, we investigated the effect of various
      concentrations of a fatty acid or corn oil on fluid intake as well as mice's
      preferences in a two-bottle choice test and a licking test. Linoleic acid (LA),
      which is a main component of corn oil, was used as a representative FFA. In the
      two-bottle choice test between a pair of different concentrations of corn oil,
      the mice consistently adopted the higher concentration of corn oil. In the
      licking test for corn oil, the licking rates for the serial concentration of corn
      oils (0, 1, 5, 10 and 100%) were increased in a concentration-dependent manner.
      On the other hand, in the two-bottle test for a pair of different concentrations
      of LA (0, 0.125, 0.25 and 1%), 0.25% and 1% LA were preferred to mineral oil, but
      0.25% and 1% LA were preferred equally in mice. In the licking test for LA, the
      mice showed the largest number of initial lickings for the 1% LA, while the
      licking rates for the high concentration of LA decreased. These results suggest
      that mice could discriminate the concentration of corn oil and LA in the oral
      cavity. We also suggest that pure corn oil is a highly preferable solution, while
      an optimal concentration of LA according to the preferences of mice is a low
      range concentration (0.25-1%).

PMID- 17459431
TI  - Ontogeny of vocalizations and movements in response to cooling in chickens
      fetuses.
AB  - Bird incubation demands a balance between parental needs for foraging with fetal
      needs for heat provision and protection so that any means of communication
      between the fetus and the parents would have an adaptive value. The aim of the
      study was to investigate whether putative avenues of feto-maternal communication
      would correlate to physiological changes caused by environmental alterations.
      Oxygen consumption was used as an indicator of fetal well being. The frequency,
      duration, intensity and composition of fetal vocalizations and the frequency and
      intensity of movements were used to evaluate the potential for communicating
      fetal status quo. Fetuses of broiler chickens (Gallus gallus domesticus) at three
      developmental stages (day 18, internally pipped and externally pipped) were
      challenged by a stepwise reduction in ambient temperature down to 30 degrees C. A
      drop in oxygen consumption in response to lowered temperatures was found in all
      stages. No differences correlating with temperature variations were found in any
      of the variables associated with fetal vocalization, even if externally pipped
      fetuses vocalized more than internally pipped fetuses. Movement occurrence and
      movement intensity, however, increased initially and decreased at temperatures
      below 35.0-35.5 degrees C. Considering that the lower limit of optimal
      development is between 35 and 36 degrees C, the results suggest that fetal
      movements can be of potential use to the incubating parent to assess and protect
      the well-being of the fetus.

PMID- 17459432
TI  - Food neophobia shows heritable variation in humans.
AB  - Food neophobia refers to reluctance to eat unfamiliar foods. We determined the
      heritability of food neophobia in a family and a twin sample. The family sample
      consisted of 28 Finnish families (105 females, 50 males, aged 18-78 years, mean
      age 49 years) and the twin sample of 468 British female twin pairs (211
      monozygous and 257 dizygous pairs, aged 17-82 years, mean age 55 years). Food
      neophobia was measured using the ten-item Food Neophobia Scale (FNS)
      questionnaire, and its internationally validated six-item modification. The
      heritability estimate for food neophobia was 69 and 66% in Finnish families
      (h(2)) and 67 and 66% in British female twins (a(2)+d(2)) using the ten- and six
      item versions of the FNS, respectively. The results from both populations suggest
      that about two thirds of variation in food neophobia is genetically determined.

PMID- 17459433
TI  - Trainees' experiences of multidisciplinary public health training schemes in
      England.
AB  - From 1999 onwards most English NHS regions launched multidisciplinary public
      health training schemes. These schemes were open to those from backgrounds other
      than medicine and followed on from the announcement of a new multidisciplinary
      Public Health Specialist post-a post equivalent to the traditional medical
      Consultant in Public Health Medicine. This article documents the issues arising
      during the first few years of the multidisciplinary public health training
      schemes. It also includes a number of case studies from trainees who have passed
      through the training schemes, examining the positive and negative experiences of
      these trainees. The paper reveals how the schemes initially varied considerably
      by region, in respect of pay and other terms and conditions. The case studies
      from ex-trainees reveal a number of positive and negative features of the
      training schemes.

PMID- 17459434
TI  - Influence of obesity on the use of sickness absence and social benefits among
      pregnant working women.
AB  - OBJECTIVE: To evaluate if obesity in early pregnancy has any possible impact on
      the capacity of pregnant women to engage in gainful employment. METHODS: Register
      data from a database on sickness absence and pregnancy benefit and parental
      benefit claims were combined with type of occupation and body mass index (BMI)
      for 693 women consecutively delivered during the course of one year at a county
      hospital in Sweden. RESULTS: The results showed the lowest BMI among women who
      had administrative jobs and the highest BMI in women who undertook more
      burdensome and heavy types of manual work. A significant increase in BMI was also
      seen among those pregnant women who were registered as unemployed. The finding
      that in the manual types of occupation, obese pregnant women took almost twice as
      many days of leave provided by the parental benefit programme as did women with a
      BMI of <25, indicates that obese pregnant women perhaps do not have the same
      physical endurance required to manage the combined demands of work and pregnancy.
      No differences were found with regard to sickness absence between obese women and
      pregnant women with normal BMI; however, differences were found between different
      occupational groups. CONCLUSIONS: Our study indicates that a woman's BMI at the
      beginning of pregnancy is associated with her occupational status. Obesity among
      pregnant women may well be used as a psychosocial indicator as obesity correlates
      with social and economic problems. Any planned weight reduction programme in
      antenatal care must therefore consider this important psychosocial aspect.

PMID- 17459435
TI  - History of multidisciplinary public health mini-symposium.

PMID- 17459436
TI  - Multidisciplinary public health: leading from the front?
AB  - This article argues that public health historically evolved in Britain as a
      multidisciplinary project. The return to its multidisciplinary roots remains an
      essential but insufficient condition for its future success. Despite its part
      emergence from the 'new public health', institutional public health is hampered
      by short-term strategies and a preoccupation with evidence when it requires a
      more powerful analysis of contemporary society, a more imaginative engagement
      with political structures culture and communications, and an embrace of
      ecological approaches in place of national public health strategies of surrogate
      consumerism.

PMID- 17459437
TI  - Comparative sequence analysis of 16S rRNA gene of Pasteurella multocida serogroup
      B isolates from different animal species.
AB  - The phylogenetic relationships of five isolates of Pasteurella multocida serotype
      B:2 belonging to buffalo, cattle, pig, sheep and goat were investigated by
      comparative sequence analysis of 16S rRNA gene. The 1468bp fragment of 16S rRNA
      gene sequence comparison showed that the isolates of cattle (PM75), pig (PM49)
      and sheep (PM82) shared 99.9% homology with the buffalo isolate (vaccine strain
      P52) whereas, the goat isolate (PM86) shared 99.8% homology with the vaccine
      strain. The 16S rRNA gene sequences of these isolates were also found
      monophyletic with type B reference strain NCTC 10323 of P. multocida subsp.
      multocida. The present study indicated the close relationships of haemorrhagic
      septicaemia causing P. multocida serotype B:2 isolates of buffalo and cattle with
      other uncommon hosts (pig, sheep and goat).

PMID- 17459438
TI  - [The pedicled submental flap].
AB  - INTRODUCTION: Facial reconstruction technique can be simple or complicated. The
      choice of performing a flap is made according to several criteria. Since its
      first description the submental flap has been used in several indications. The
      aim of this article was to document maxillofacial surgeons on this flap
      technique. ANATOMY: The submental artery is a major branch of the facial artery.
      This artery runs medial to the mandible and ends next to the mandibular
      symphysis. The submental artery supplies the submandibular lymph nodes,
      submandibular salivary gland, mylohyoid and digastric muscles, and the skin of
      the chin. The submental vein drains the tissues of the chin as well as the
      submandibular region. TECHNIQUE: The integrity of the facial artery is a sine qua
      none condition before performing this flap. It is important that the
      submandibular gland and the submental vessels be well exposed. The anterior belly
      of the homolateral digastric muscle must be included in the flap. The donor side
      is closed after a large subcutaneous dissection of the neck and chin.
      INDICATIONS: The pedicled submental flap is indicated in defects of the oral
      cavity and the lower two-thirds of the face. ADVANTAGES: The submental flap is
      relatively easy to raise. This flap avoids dyschromia and provides soft-tissues
      presenting with the same quality as that of the tissue surrounding the defect.
      Sequels on the donor side are minor. DISADVANTAGES: The submental flap is not
      indicated if a submental neck dissection is needed or in case of
      intraoral/frontal reconstruction with bearded skin. The submental flap is a
      simple and reliable procedure, with good aesthetics results and minor sequels.

PMID- 17459439
TI  - [Pleomorphic adenoma of the tongue base].
AB  - INTRODUCTION: Pleomorphic adenoma is the most common lesion of minor salivary
      glands but is exceptional in the tongue base. REPORT CASE: We report the case of
      a 70-year-old woman with pleomorphic adenoma of the tongue base. The patient
      consulted for difficult swallowing, which developed over 4 months. Physical
      examination and computed tomography revealed a cystic tumour located in the right
      side of tongue base. The tumor was removed by transoral resection. The
      histological examination demonstrated a pleomorphic adenoma. DISCUSSION: We will
      discuss the diagnostic and therapeutically modalities of pleomorphic adenoma of
      the tongue base with a review of the literature.

PMID- 17459440
TI  - [Surgical management of mandibular condylar fractures in adults in France, 2005].
AB  - INTRODUCTION: The authors had for aim to present the latest trends in the
      surgical management of mandibular condylar fractures in France, in 2005. MATERIAL
      AND METHODS: One hundred maxillofacial surgeons were questioned on the surgical
      management of condylar fractures and indications. Results were presented at the
      41st Congress of Stomatology and Maxillofacial surgery. RESULTS: The overall
      reply rate was 70%. Condylar fractures are generally managed in teaching
      hospitals. Open reduction and fixation was deemed appropriate in low subcondylar
      fractures in 76% of the cases, in 10% for diacapitular fractures. Therapeutic
      details and indications were a matter of huge variability. DISCUSSION: This
      survey highlighted the absence of any consensus as far as condylar fractures are
      concerned. It seems that the higher the fractures are, the lesser they are
      approached.

PMID- 17459441
TI  - Biological stress response terminology: Integrating the concepts of adaptive
      response and preconditioning stress within a hormetic dose-response framework.
AB  - Many biological subdisciplines that regularly assess dose-response relationships
      have identified an evolutionarily conserved process in which a low dose of a
      stressful stimulus activates an adaptive response that increases the resistance
      of the cell or organism to a moderate to severe level of stress. Due to a lack of
      frequent interaction among scientists in these many areas, there has emerged a
      broad range of terms that describe such dose-response relationships. This
      situation has become problematic because the different terms describe a family of
      similar biological responses (e.g., adaptive response, preconditioning,
      hormesis), adversely affecting interdisciplinary communication, and possibly even
      obscuring generalizable features and central biological concepts. With support
      from scientists in a broad range of disciplines, this article offers a set of
      recommendations we believe can achieve greater conceptual harmony in dose
      response terminology, as well as better understanding and communication across
      the broad spectrum of biological disciplines.

PMID- 17459442
TI  - Inhibition of initiation of reverse transcription in HIV-1 by human APOBEC3F.
AB  - Vif-negative HIV-1 produced in non-permissive human cells incorporate both
      APOBEC3F (hA3F) AND APOBEC3G (hA3G), and have a severely reduced ability to
      produce viral DNA in newly infected cells. While it has been proposed that this
      reduction is due to deamination of deoxycytidine in viral DNA by either hA3G or
      hA3F, followed by DNA degradation, recent evidence indicates that the inhibition
      of viral DNA production can occur independently of DNA editing by either hA3F or
      hA3G. We have reported that the presence of hA3G in Vif-negative HIV-1 produced
      from either the non-permissive cell line, H9, or from transfected 293T cells
      transiently or stably expressing hA3G, results in a >or=50% reduction in the
      ability of primer tRNA(Lys3) to initiate reverse transcription in these virions,
      and that this is correlated with a similar reduction in the production of early
      DNA transcripts in the infected cells. In this work, we show that, like hA3G,
      hA3F in Vif-negative virions also results in a similar reduction in the
      initiation of reverse transcription in HIV-1, which is correlated with the
      inhibition of early viral DNA synthesis in the cell, and which does not require
      cytidine-deamination of DNA.

PMID- 17459443
TI  - The Autographa californica M nucleopolyhedrovirus fibroblast growth factor
      accelerates host mortality.
AB  - The fibroblast growth factor (vfgf) gene encoded by Autographa californica M
      nucleopolyhedrovirus (AcMNPV) has been shown to share functional properties with
      cellular fgfs; it is a secreted protein, binds heparin, and stimulates motility
      of insect cells. We previously reported that viruses containing or lacking vfgf
      produced similar yields of budded virus and had similar kinetics of viral DNA and
      protein syntheses in cultured cells. In this study, we characterized these
      viruses in two permissive hosts, Spodoptera frugiperda and Trichoplusia ni, using
      two insect developmental stages and two infection routes, by feeding and
      intrahemocoelic injection. In addition, we constructed an AcMNPV bacmid
      overexpressing vfgf under polyhedrin promoter control and characterized it in
      both cell culture and insects. Deletion of vfgf had no effect on the infectivity
      of AcMNPV. However, lack of vfgf delayed the time of death in two host species
      when the virus was delivered by feeding but not by intrahemocoelic injection. The
      virus overexpressing vfgf produced less budded virus than the control virus in
      cultured cells. In insect bioassays, the infectivity of this virus was greater
      than that of the parental virus in both insect species and significantly
      accelerated time of death of both hosts tested. Our results suggest that the
      AcMNPV vfgf may play a role in dissemination of virus infection from the midgut
      in the insect species tested.

PMID- 17459444
TI  - Analysis of the genome sequence of an alpaca coronavirus.
AB  - Coronaviral infection of New World camelids was first identified in 1998 in
      llamas and alpacas with severe diarrhea. In order to understand this infection,
      one of the coronavirus isolates was sequenced and analyzed. It has a genome of
      31,076 nt including the poly A tail at the 3' end. This virus designated as ACoV
      00-1381 (ACoV) encodes all 10 open reading frames (ORFs) characteristic of Group
      2 bovine coronavirus (BCoV). Phylogenetic analysis showed that the ACoV genome is
      clustered closely (>99.5% identity) with two BCoV strains, ENT and LUN, and was
      also closely related to other BCoV strains (Mebus, Quebec, DB2), a human corona
      virus (strain 043) (>96%), and porcine hemagglutinating encephalomyelitis virus
      (>93% identity). A total of 145 point mutations and one nucleotide deletion were
      found relative to the BCoV ENT. Most of the ORFs were highly conserved; however,
      the predicted spike protein (S) has 9 and 12 amino acid differences from BCoV LUN
      and ENT, respectively, and shows a higher relative number of changes than the
      other proteins. Phylogenetic analysis suggests that ACoV shares the same ancestor
      as BCoV ENT and LUN.

PMID- 17459445
TI  - Inhibition of human immunodeficiency virus type 1 transcription by N
      aminoimidazole derivatives.
AB  - This study describes the mechanism of antiviral action of the N-aminoimidazole
      derivatives which exclusively inhibit retroviruses such as HIV-1, HIV-2, SIV and
      MSV. These antiretroviral compounds, with lead prototype NR-818, were found to
      inhibit HIV-1 replication at the transcriptional level. Analysis of each
      individual step of viral transcription, including transcriptional activation
      mediated by NF-kappaB, the chromatin remodeling process at the viral promoter and
      viral mRNA transcription mediated by RNAPII, showed that NR-818 was able to
      prolong the binding of NF-kappaB to its consensus sequence. The compound also
      increased the acetylation of histones H3 and H4 within the nucleosome nuc-1 at
      the transcription initiation site and inhibited the recruitment of viral Tat and
      the phosphorylation of the RNA polymerase II C-terminal domain (RNAPII CTD) at
      the viral promoter upon stimulation of latently HIV-1-infected cell lines. As a
      result, viral mRNA expression and subsequent viral p24 production in stimulated
      latently HIV-1-infected cell lines was suppressed by NR-818. These data suggest
      that the N-aminoimidazole derivatives effectively inhibit the reactivation of HIV
      1 and may contribute to the control of the latent HIV-1 reservoir.

PMID- 17459447
TI  - Filtering items of mass distraction: top-down biases against distractors are
      necessary for the feature-based carry-over to occur.
AB  - In preview search a new target is difficult to detect if it carries a feature
      shared with the old distractors [Braithwaite, J. J., Humphreys, G. W., & Hodsoll,
      J. (2003). Color grouping in space and time: Evidence from negative color-based
      carry-over effects in preview search. Journal of Experimental Psychology: Human
      Perception and Performance, 29(4), 758-778.] Two experiments are presented which
      examined whether this negative color carry-over effect is dependent on an
      attentional-set to ignore old, irrelevant distractors. Consistent with this, the
      data show that the negative carry-over effect is greatly reduced if the
      attentional-set to ignore the old preview items is removed and replaced by a set
      to prioritize the old items instead. The findings demonstrate that preview
      search, and the carry-over effect, are at least partly determined by a top-down
      intentional bias against old, irrelevant information.

PMID- 17459446
TI  - TLR-4 and -6 agonists reverse apoptosis and promote maturation of simian virus 5
      infected human dendritic cells through NFkB-dependent pathways.
AB  - Infection of primary cultures of human immature monocyte-derived dendritic cells
      (moDC) with the paramyxovirus Simian Virus 5 (SV5) results in extensive
      cytopathic effect (CPE) and induction of apoptosis, but DC maturation pathways
      are not activated. In this study, we investigated the relationship between SV5
      induced apoptosis and the lack of DC maturation. Reducing CPE and apoptosis in
      SV5-infected immature DC by the addition of a pancaspase inhibitor resulted in
      only low level expression of maturation markers CD40, CD80 and CD86, suggesting
      that SV5 infection either actively blocked maturation pathways or failed to
      provide sufficient signals to activate maturation. To distinguish between these
      hypotheses, SV5-infected immature DC were challenged with agonists that stimulate
      toll-like receptors (TLRs). Treatment with the TLR-4 agonist LPS or TLR-6 agonist
      FSL1 enhanced cell surface expression of CD40, CD80 and CD86 on SV5-infected
      cells to levels approaching that of mock-infected TLR-treated moDC, but treatment
      with agonists for TLR-2, -3, -5 or -8 had little effect. Addition of TLR-4 or -6
      agonists to SV5-infected DC also dramatically reduced CPE and apoptosis, but the
      levels of viral protein and virus yield were not affected. Similarly, SV5
      infected immature moDC were matured by treatment with IL-1beta, and these mature
      infected cells also showed reduced CPE and apoptosis. In the presence of NFkB
      inhibitors, TLR-4 and -6 agonists did not promote maturation or reduce apoptosis
      of SV5-infected DC, indicating that maturation and cell survival were both
      dependent on signaling through NFkB-dependent pathways. Our results suggest a
      model whereby SV5 replication induces apoptosis in immature DC but fails to
      provide strong maturation signals, while activation of NFkB-dependent pathways by
      exogenous ligands can lead to moDC maturation and override SV5-induced cell
      death.

PMID- 17459448
TI  - Explaining brightness illusions using spatial filtering and local response
      normalization.
AB  - We introduce two new low-level computational models of brightness perception that
      account for a wide range of brightness illusions, including many variations on
      White's Effect [Perception, 8, 1979, 413]. Our models extend Blakeslee and
      McCourt's ODOG model [Vision Research, 39, 1999, 4361], which combines multiscale
      oriented difference-of-Gaussian filters and response normalization. We extend the
      response normalization to be more neurally plausible by constraining
      normalization to nearby receptive fields (models 1 and 2) and spatial frequencies
      (model 2), and show that both of these changes increase the effectiveness of the
      models at predicting brightness illusions.

PMID- 17459449
TI  - Biosorption of arsenic (V) with acid-washed crab shells.
AB  - Highly toxic arsenate occurs naturally in some well water as well as in
      industrial wastewaters. Removal of arsenate (As(V)) by biosorption with acid
      washed crab shells (AWCS) is very sensitive to solution pH. It greatly increased
      when the solution pH was lowered from 3.44+/-0.07 to 2.51+/-0.02, but it was
      reduced at pH below 1.99+/-0.01. Change of solution pH not only affected the
      charged functional groups on AWCS but also the speciation of arsenate in
      solution. Increasing ionic strength of solution negatively affected the arsenic
      uptake. At ionic strength 0.1M, arsenic uptake was seriously depressed. Arsenic
      biosorption with AWCS was mainly through arsenate binding on the amide groups in
      the AWCS. AWCS has a dense structure and low extent of swelling in aqueous
      solutions. This might prevent effective arsenate access to the functional groups
      in AWCS.

PMID- 17459450
TI  - The quest for safe drinking water: an example from Guinea-Bissau (West Africa).
AB  - While humans require water for life, one-sixth of our species lives without
      access to safe water. In Africa, the situation is particularly acute because of
      global warming, the progression of the Sahara desert, civil unrest and poor
      governance, population growth, migration and poverty. In rural areas, the lack of
      adequate safe water and sanitary infrastructures leaves millions with doubtful
      water quality, increasing the harshness of daily life. In this paper, a pilot
      study was conducted during the wet season on Bolama Island (Guinea-Bissau, West
      Africa), a UNESCO Man and the Biosphere Reserve. Twenty-eight shallow wells,
      supplying water to most of the population, were sampled for microbiological,
      physical and chemical water quality characteristics. A ten-parameter water
      quality index (WQI) adapted to tropical conditions was applied to compare the
      different wells. About 79% of the wells showed moderate to heavy fecal
      contamination. From the surveyed parameters, it was found that chemical
      contamination was less important, although all samples were acidic, with the pH
      averaging 5.12+/-0.08. The WQI was 43+/-4% (0%-worst; 100%-best quality), showing
      that the water from the majority of wells was polluted but should be suitable for
      domestic use after appropriate treatment. At the onset of the wet season,
      diarrhea represented 11.5% of all medical cases, 92.5% of which were children
      aged <15. This paper suggests inexpensive steps to reduce the fecal contamination
      and control the pH in order to increase the potability of the well water and,
      concomitantly, to raise the living standards of the population in one of the
      poorest countries of the world.

PMID- 17459451
TI  - Effect of nonionic surfactants on the oxidation of carbaryl by anodic Fenton
      treatment.
AB  - As a potentially promising technology, anodic Fenton treatment (AFT) has been
      shown to be very successful in pesticide removal. However, the influence of other
      constituents in the pesticide formulation, such as nonionic surfactants, has not
      been addressed. In this study, the effect of Triton X (TX) on the degradation
      kinetics and pathways of carbaryl undergoing AFT was investigated in an effort to
      facilitate its practical application. The presence of Triton X-100 was found to
      slow down the carbaryl degradation rate. This result can be attributed to the
      consumption of hydroxyl radicals ((*)OH) by surfactants and the formation of a
      carbaryl...TX...Fe(3+) complex, resulting in the unavailability of carbaryl to
      (*)OH attack. The modified AFT kinetic model previously developed in this
      laboratory shows an excellent fit to the carbaryl degradation profile
      (R(2)>0.998), supporting the formation of a carbaryl...TX...Fe(3+) complex. The
      carbaryl degradation rate decreased as Triton X-100 concentration increased from
      20 to 1000 mg L(-1). Both (*)OH consumption by surfactants and complex formation
      are responsible for the degradation rate reduction below the critical micelle
      concentration (CMC), whereas the complex and micelle formation becomes a more
      dominant factor above the CMC. The effect of ethylene oxide (EO) numbers of a
      given nonionic surfactant mainly lies in the consumption of hydroxyl radicals,
      which increases with the length of the EO chain, but does not significantly
      affect the formation of the carbaryl...TX...Fe(3+) complex. Based on the GC-MS
      and LC-ESI-MS results, no evidence was found that the carbaryl degradation
      pathway was affected. Carbaryl was typically oxidized to 1-naphthol and 1,4
      naphthoquinone similar to what is observed in the absence of surfactants. Triton
      X-100 was degraded via the breakdown of EO chains and omega-oxidation of the
      terminal methyl group, which resulted in the production of a series of ethoxylate
      oligomers.

PMID- 17459452
TI  - Organic micropollutants degradation in ozone-loaded system with perfluorinated
      solvent.
AB  - In order to provide higher ozonation process efficiency, new methods of advanced
      oxidation have been investigated. One of them is two-phase ozonation, sometimes
      called as ozone-loaded system. In this study, the solubility and stability of
      ozone in Fluorinet FC40 as well as the influence of pH and contact time on
      diffusion rate of oxidant from saturated FC40 phase to water was examined. The
      main purpose of this paper is to compare the removal efficiency of organic
      compounds with different distribution coefficient (K(D)) in conventional and
      ozone-loaded systems as well as to reveal the mechanism of the process. It is
      shown that organic micropollutants with high K(D) diffuse into FC40 where
      degradation reaction takes place. In a case of compounds with high polarity the
      perfluorinated phase works as ozone reservoir. The results indicated that oxidant
      is gradually released from FC40 into the water. In consequence, the oxidation
      reaction occurs in water, not in perfluorinated phase as it has been so far
      presumed.

PMID- 17459453
TI  - Chemical status of selenium in evaporation basins for disposal of agricultural
      drainage.
AB  - Evaporation basins (or ponds) are the most commonly used facilities for disposal
      of selenium-laden saline agricultural drainage in the closed hydrologic basin
      portion of the San Joaquin Valley, California. However concerns remain for
      potential risk from selenium (Se) toxicity to water fowl in these evaporation
      basins. In this study, we examined the chemical status of Se in both waters and
      sediments in two currently operating evaporation pond facilities in the Tulare
      Lake Drainage District. Some of the saline ponds have been colonized by brine
      shrimp (Artemia), which have been harvested since 2001. We evaluated Se
      concentration and speciation, including selenate [Se(VI)], selenite [Se(IV)], and
      organic Se [org-Se or Se(-II)] in waters and sediment extracts, and fractionation
      (soluble, adsorbed, organic matter (OM)-associated, and Se(0) and other resistant
      forms) in sediments and organic-rich surface detrital layers from the decay of
      algal blooms. Selenium in ponds without vascular plants exhibited similar
      behavior to wetlands with vascular plant present, indicating that similar Se
      transformation processes and mechanisms had resulted in Se immobilization and an
      increase of reduced Se species [Se(IV), org-Se, and Se(0)] from Se(VI)-dominated
      input waters. Selenium concentrations in most pond waters were significantly
      lower than the influent drainage water. This decrease of dissolved Se
      concentration was accompanied by the increase of reduced Se species. Selenium
      accumulated preferentially in sediments of the initial pond cell receiving
      drainage water. Brine-shrimp harvesting activities did not affect Se speciation
      but may have reduced Se accumulation in surface detrital and sediments.

PMID- 17459454
TI  - Predicting cadmium adsorption on soils using WHAM VI.
AB  - Cadmium (Cd) adsorption on 14 non-calcareous New Jersey soils was investigated
      with a batch method. Both adsorption edge and isotherm experiments were conducted
      covering a wide range of soil composition, e.g. soil organic carbon (SOC)
      concentration ranging from 0.18% to 7.15%, and varying Cd concentrations and
      solution pH. The SOC and solution pH were the most important parameters
      controlling Cd partition equilibrium between soils and solutions in our
      experimental conditions. The Windermere humic aqueous model (WHAM) was used to
      calculate Cd adsorption on soils. The effect of solution chemistry (various pH
      and Cd concentrations) on Cd adsorption can be well accounted for by WHAM. For
      different soil compositions, SOC concentration is the most important parameter
      for Cd binding. Only a fraction of SOC, the so-called active organic carbon
      (AOC), is responsible for Cd binding. We found a linear relationship between SOC
      and AOC based on the adsorption edge data. The linear relationship was validated
      by the independent data sets: adsorption isotherm data, which presumably can be
      used to predict Cd partition equilibrium across a wide range of soil
      compositions. The modeling approach presented in this study helps to
      quantitatively predict Cd behavior in the environment.

PMID- 17459455
TI  - Analyses of human-chimpanzee orthologous gene pairs to explore evolutionary
      hypotheses of aging.
AB  - Compared to chimpanzees (Pan troglodytes), the onset of aging appears to be
      delayed in the human species. Herein, we studied human-chimpanzee orthologous
      gene pairs to investigate the selective forces acting on genes associated with
      aging in different model systems, which allowed us to explore evolutionary
      hypotheses of aging. Our results show that aging-associated genes tend to be
      under purifying selection and stronger-than-average functional constraints. We
      found little evidence of accelerated evolution in aging-associated genes in the
      hominid or human lineages, and pathways previously related to aging were largely
      conserved between humans and chimpanzees. In particular, genes associated with
      aging in non-mammalian model organisms and cellular systems appear to be under
      stronger functional constraints than those associated with aging in mammals. One
      gene that might have undergone rapid evolution in hominids is the Werner syndrome
      gene. Overall, our findings offer novel insights regarding the evolutionary
      forces acting on genes associated with aging in model systems. We propose that
      genes associated with aging in model organisms may be part of conserved pathways
      related to pleiotropic effects on aging that might not regulate species
      differences in aging.

PMID- 17459457
TI  - Measurements of daily urinary uranium excretion in German peacekeeping personnel
      and residents of the Kosovo region to assess potential intakes of depleted
      uranium (DU).
AB  - Following the end of the Kosovo conflict, in June 1999, a study was instigated to
      evaluate whether there was a cause for concern of health risk from depleted
      uranium (DU) to German peacekeeping personnel serving in the Balkans. In
      addition, the investigations were extended to residents of Kosovo and southern
      Serbia, who lived in areas where DU ammunitions were deployed. In order to assess
      a possible DU intake, both the urinary uranium excretion of volunteer residents
      and water samples were collected and analysed using inductively coupled plasma
      mass spectrometry (ICP-MS). More than 1300 urine samples from peacekeeping
      personnel and unexposed controls of different genders and age were analysed to
      determine uranium excretion parameters. The urine measurements for 113 unexposed
      subjects revealed a daily uranium excretion rate with a geometric mean of 13.9
      ng/d (geometric standard deviation (GSD)=2.17). The analysis of 1228 urine
      samples from the peacekeeping personnel resulted in a geometric mean of 12.8 ng/d
      (GSD=2.60). It follows that both unexposed controls and peacekeeping personnel
      excreted similar amounts of uranium. Inter-subject variation in uranium excretion
      was high and no significant age-specific differences were found. The second part
      of the study monitored 24 h urine samples provided by selected residents of
      Kosovo and adjacent regions of Serbia compared to controls from Munich, Germany.
      Total uranium and isotope ratios were measured in order to determine DU content.
      (235)U/(238)U ratios were within +/-0.3% of the natural value, and (236)U/(238)U
      was less than 2 x 10(-7), indicating no significant DU in any of the urine
      samples provided, despite total uranium excretion being relatively high in some
      cases. Measurements of ground and tap water samples from regions where DU
      munitions were deployed did not show any contamination with DU, except in one
      sample. It is concluded that both peacekeeping personnel and residents serving or
      living in the Balkans, respectively, were not exposed to significant amounts of
      DU.

PMID- 17459456
TI  - A common variant of the p16(INK4a) genetic region is associated with physical
      function in older people.
AB  - p16(INK4a) is active in cell senescence, ageing and tumor suppression. Deletion
      of the small p16(INK4a)/ARF/p15(INK4b) region occurs in many cancers. We screened
      25 common polymorphisms across the region and three related genes for
      associations with physical functioning in older people. In an initial sample of
      938 (aged 65-80 years) from the EPIC study (Norfolk, UK), the rs2811712 SNP minor
      allele (located between the shared p16(INK4a)/ARF locus and p15(INK4b)) was
      associated with reduced physical impairment. This association remained after
      testing an additional 1319 EPIC-Norfolk samples (p-value=0.013, total n=2257),
      and on independent replication in the InCHIANTI study (n=709, p=0.015), and at
      one-sided significance in Iowa-EPESE (n=419, p=0.079). Overall (n=3372), the
      prevalence of severely limited physical function was 15.0% in common homozygotes
      and 7.0% in rare homozygotes (per minor allele odds ratio=1.48, 95% CI: 1.17
      1.88, p=0.001, adjusted for age, sex and study). This estimate was similar
      excluding screening set 1 (OR=1.45, 95% CI: 1.09-1.92, p=0.010, n=2434). These
      findings require further replication, but provide the first direct evidence that
      the p16(INK4a)/ARF/p15(INK4b) genetic region and the senescence machinery are
      active in physical ageing in heterogeneous human populations. The mechanism
      involved may be via greater cellular restorative activity and reduced stem cell
      senescence.

PMID- 17459458
TI  - Carbon losses from soil and its consequences for land-use management.
AB  - This paper reviews our current knowledge and understanding of carbon processes in
      the terrestrial ecosystem with a view to reducing soil carbon losses by
      optimising land-use and land management. Processes that influence the fate of
      carbon (in both terms of quantity and quality) are important in determining soil
      fertility, quality and health as well as consequences for future environmental
      change scenarios. We need to understand the processes that determine soil carbon
      losses and the fate of the carbon once lost from the soil in order to provide
      sustainable solutions for mitigating these carbon losses as part of land
      management "best practice" and balancing national carbon budgets. Here we review
      the amount of carbon within the UK terrestrial pool, the processes involved and
      factors influencing carbon transport to and from soils, the fate of the carbon
      once it has been lost from the soil environment and land-use scenarios that
      affect carbon losses. We conclude with possible management options to reduce soil
      carbon loss and identify gaps in knowledge in order to better understand carbon
      processes in the terrestrial environment.

PMID- 17459459
TI  - Plutonium and 137Cs in surface water of the South Pacific Ocean.
AB  - The present plutonium and 137Cs concentrations in South Pacific Ocean surface
      waters were determined. The water samples were collected in the South Pacific mid
      latitude region (32.5 degrees S) during the BEAGLE expedition conducted in 2003
      04 by JAMSTEC. 239,240Pu concentrations in surface seawater of the South Pacific
      were in the range of 0.5 to 4.1 mBq m(-3), whereas 137Cs concentrations ranged
      from 0.07 to 1.7 Bq m(-3). The observed 239,240Pu and 137Cs concentrations in the
      South Pacific were almost of the same level as those in the North Pacific
      subtropical gyre. The surface 239,240Pu in the South Pacific subtropical gyre
      showed larger spatial variations than 137Cs, as it may be affected by physical
      and biogeochemical processes. The 239,240Pu/137Cs activity ratios, which reflect
      biogeochemical processes in seawater, were generally smaller than that observed
      in global fallout, except for the most eastern station. The 239,240Pu/137Cs
      ratios in the South Pacific tend to be higher than that in the North Pacific. The
      relationships between anthropogenic radionuclides and oceanographic parameters
      such as salinity and nutrients were examined. The 137Cs concentrations in the
      western South Pacific (the Tasman Sea) and the eastern South Pacific were
      negatively correlated with the phosphate concentration, whereas there is no
      correlation between the 137Cs and nutrients concentrations in the South Pacific
      subtropical gyre. The mutual relationships between anthropogenic radionuclides
      and oceanographic parameters are important for better understanding of transport
      processes of anthropogenic radionuclides and their fate in the South Pacific.

PMID- 17459460
TI  - The magnetic properties of particles deposited on Platanus x hispanica leaves in
      Madrid, Spain, and their temporal and spatial variations.
AB  - Magnetic phases are a common component of atmospheric particles and as such are
      being increasingly exploited in air quality studies. In this context the magnetic
      properties of Platanus x hispanica leaves were determined during the spring and
      summer months of 2001 and 2004 in Madrid, Spain. The leaves exhibited a stable
      magnetic signal carried by partially oxidized magnetite grains. Most or all of
      the material resided on the leaf surfaces as a net result of accumulation with
      time and removal through precipitation. Concentration and grain-size trends
      indicated that roads act as the source of the magnetic signal. The relationships
      between IRM(1T) (magnetic concentration) and the concentration of NO(x) and
      PM(10) showed that the magnetic signal is specific to traffic-related emissions
      and not to total particle mass. City-wide maps of magnetic concentration were
      produced which describe the medium-term net accumulation of traffic-related
      particles. They showed the same pattern of concentration lows and highs in both
      years, with lower concentrations in 2004. Consistently high values were observed
      in south-central Madrid, in an area of high traffic activity. The effects of
      precipitation make establishing quantitative relationships between magnetic
      concentration and air quality parameters difficult when using tree leaves as a
      passive sampling system. However, a qualitative relationship is maintained which
      permits the mapping and identification of persistent features of particle
      accumulation.

PMID- 17459461
TI  - Prognostic factors and role of salvage surgery in chemorefractory ovarian germ
      cell malignancies: a study in Chinese patients.
AB  - BACKGROUND AND OBJECTIVES: The majority of the studies on ovarian germ cell
      malignancies (OGCMs) focused on combination chemotherapy and fertility sparing
      surgery in primary treatment. Prognostic factors and the salvage treatment,
      particularly the role of salvage surgery, for the chemorefractory disease are
      much less documented. The purpose of this study was to explore the prognostic
      factors and the role of salvage surgery in Chinese patients with chemorefractory
      OGCMs. METHODS: A total of 34 patients with chemorefractory OGCMs who underwent
      salvage surgery at Fudan University Cancer Hospital from April 1992 to December
      2005 were retrospectively identified and analyzed. Survival was analyzed using
      the Kaplan-Meier and the statistical significance of various prognostic factors
      was tested using both the log-rank and the Cox proportional hazards models.
      RESULTS: The median age of the study patients was 22.76 years. The histological
      subtypes included 2 dysgerminomas (DSG), 7 immature teratomas (IMT), 22
      endodermal sinus tumors (EST) (including 16 pure EST, 3 mixed type with DSG, 3
      with EC), 2 embryonal carcinomas (EC) and 1 mixed form (with component of sex
      cord-stromal tumor). The median follow-up time was 44.09 months (range, 5-164
      months). For the entire study population, 1-, 3-, and 5-year survival were
      82.35%, 45.64%, and 33.17%, respectively. The 1-, 3-, and 5-year survival in
      patients who were rendered macroscopically disease-free or had residual disease <
      or = 1 cm after surgical salvage were 93.33%, 80.00%, and 60.95%, compared to
      68.42%, 21.05%, and 14.04% in those who had postoperative residual disease >1 cm
      (P=0.0036). Histology (DSG/IMT vs. non-DSG/IMT) (P=0.0221), primary and salvage
      chemotherapy regimen (non-BEP/PVB regimen for primary chemotherapy and BEP/PVB
      regimen for salvage chemotherapy vs. all other regimens in primary and salvage
      chemotherapy) (P=0.0316), site of chemorefractory disease (retroperitoneal vs.
      intraperitoneal) (P=0.0221), and salvage surgery states (optimal cytoreduction
      vs. suboptimal cytoreduction) (P=0.0036) were significant prognostic factors for
      survival through univariate analysis. However, site of chemorefractory disease
      was excluded as an independent prognostic factor according to multivariate
      analysis. CONCLUSIONS: Chemorefractory cases with dysgerminoma or immature
      teratoma appear to have better outcome than the other subtypes. When offered
      standard BEP/PVB regimen as salvage chemotherapy, patients with chemorefractory
      disease after non-BEP/PVB primary chemotherapy have better prognosis. Optimal
      cytoreduction during salvage surgery does benefit chemorefractory patients.

PMID- 17459463
TI  - Potential risk of equine herpes virus 1 (EHV-1) transmission by equine embryo
      transfer.
AB  - The objective of this study was to determine whether the 10 wash cycles proposed
      by the International Embryo Transfer Society (IETS) for bovine embryos
      efficiently decontaminated equine embryos exposed to equine herpes virus 1 (EHV
      1) in vitro. Donor mares and stallions were individually screened and shown to be
      negative for the virus by PCR detection of EHV-1 DNA in blood leukocytes, semen,
      and uterine lavages in which embryos were recovered. Twenty embryos were
      recovered and randomly assigned to one of two groups: 10 embryos were exposed for
      24h to infectious EHV-1 at 10(6)TCID(50)/ml, and 10 embryos were used as negative
      controls. Exposed embryos were washed in accordance with IETS recommendations for
      ruminant and porcine embryos, before being incubated for 24 h with semiconfluent
      rabbit kidney (RK13) cells to detect any cytopathic effects (CPE), and finally
      tested for the presence of EHV-1 viral DNA by PCR. The embryo washing media were
      also assayed for the virus on RK 13 cells and by PCR. Control embryos were
      neither exposed to the virus nor washed. EHV-1 was not found in the control
      embryos, or in the last five washes of the exposed embryos. However, the virus
      was detected in 7/10 of the embryos exposed to EHV-1 for 24h, as well as in the
      first five washes of the embryos. The gradual disappearance of EHV-1 from the 10
      successive wash solutions from the exposed embryos and the detection of viral DNA
      in 7/10 washed embryos by PCR, demonstrated that the washing procedure was unable
      to remove EHV-1 and suggested that EHV-1 could be attached to the acellular layer
      surrounding embryos (zona pellucida or capsule) or had penetrated the embryo.

PMID- 17459462
TI  - Enhanced sensitivity to naltrexone-induced drinking suppression of fluid intake
      and sucrose consumption in maternally separated rats.
AB  - Early-life stress has been identified as a risk factor in the development of a
      host of disorders, including substance abuse; however the link between early
      postnatal stress and changes in measures of reward has not been thoroughly
      researched. The current study had two main objectives: 1) to determine the impact
      of maternal separation (an animal model of early-life stress) on the consumption
      of 10% and 2.5% sucrose solutions by Long-Evans rat dams and male and female
      offspring, and 2) to determine the effect of the opioid antagonist naltrexone
      (0.1-3.0 mg/kg) on drinking by each of those groups. Dam-pup separations occurred
      for varying lengths of time during the first two postnatal weeks. In Experiment
      1, a two-bottle choice test (sucrose solution vs. water) was administered across
      five days to both nonhandled (NH) and maternally-separated (MS) offspring as
      adults and to dams 2-4 weeks post-weaning. In Experiment 2, naltrexone was
      administered prior to two-bottle choice tests. MS males and the dams of MS
      litters exhibited increased intake of total fluid and sucrose solutions, whereas
      results from females were less consistent. Naltrexone elicited a greater decrease
      in fluid intake and sucrose intake in male MS offspring compared to male NH
      offspring. These results indicate that early postnatal stress alters both sucrose
      consumption, a non-drug measure of reward, and apparently the brain opioid
      systems that mediate naltrexone-induced drinking suppression.

PMID- 17459464
TI  - Influence of progesterone concentrations on secretory functions of trophoblast
      and pituitary during the first trimester of pregnancy in dairy cattle.
AB  - The essential role played by progesterone in the maintenance of pregnancy is
      unequivocal; however, the effects of progesterone on the secretory patterns of
      placental and pituitary molecules during the gestation period are not well
      defined. The objective of this study was to describe pregnancy-associated
      glycoprotein (PAG) concentrations (measured by RIA-497 and RIA-Pool) in pregnant
      females with progesterone concentrations lower (low-P4 group, n=20) or higher
      (high-P4 group, n=17) than the mean of 8.74 ng/mL on Day 21 (AI=Day 0).
      Luteinizing hormone (LH) and prolactin concentrations were also measured in both
      groups. Throughout the study period, blood samples were collected on Days 0, 21,
      45, 60, and 80 from 37 females that were confirmed to be pregnant. PAG
      concentrations measured by both RIA-497 and RIA-Pool tended to be higher in high
      P4 group than in low-P4 group from Day 30 until Day 80. On Day 80, plasma PAG
      concentrations that were measured using RIA-497 were observed to be higher
      (P<0.05) in the high-P4 group than in the low-P4 group (10.2+/-8.7 ng/mL versus
      6.9+/-3.8 ng/mL). Concentrations of LH on Day 60 and prolactin on Day 80 were
      observed to be significantly lower (P<0.05) in the high-P4 group. There was a
      tendency for the concentrations of LH (Days 45 and 80) and prolactin (Days 30,
      45, and 60) to be lower in cows in the high-P4 group than in the low-P4 group.
      Our results suggest the existence of a relationship among the concentration
      levels of progesterone, PAG, LH, and prolactin during early pregnancy.

PMID- 17459465
TI  - Evaluation of a modified surgical technique to correct urine pooling in cows.
AB  - Various surgical techniques to correct urovagina in cows describe creating a
      mucosal extension from the urethral orifice to the labia; however, a fistula
      often forms in the mucosal extension. The objective of the present study was to
      determine if the incidence of fistula formation could be decreased by covering
      transposed submucosal tissue on the dorsal aspect of the urethral extension with
      a mucosal graft. Cows in both the control group (19) and the experimental group
      (19) received a modified McKinnon technique of urethral extension; cows in the
      experimental group also had a sheet of mucosa, obtained from the dorsal aspect of
      the vestibule, grafted to submucosa exposed during creation of the urethral
      extension. During histological examination of the biopsy of the graft and its
      recipient site (harvested 1 week after surgery), neither inosculation nor
      revascularization of the graft was evident in any sample. Fourteen of 19 (74%)
      cows in the control group and 10 of 19 (53%) cows in the experimental group
      developed a fistula in the extension (P=0.18). We concluded that application of a
      mucosal graft to the subcutaneous tissue exposed to the vestibule using the
      McKinnon technique of creating a urethral extension was of little or no benefit
      in preventing the formation of a fistula in the extension. Furthermore, during
      evaluation of the extensions, digital palpation alone was often insufficient for
      detection of a fistula.

PMID- 17459466
TI  - Kinetic studies of the effect of varnish on water loss by glass-ionomer cements.
AB  - OBJECTIVES: This paper reports a study of the water loss behaviour of two
      commercial glass-ionomer cements coated with varnishes. METHODS: For each cement
      (Fuji IX Fast or Chemflex), specimens (6mmdiameterx2mm depth) were prepared and
      cured for 10min at 37 degrees C. They were exposed to a desiccating environment
      over H(2)SO(4) either uncoated or coated with the appropriate varnish (Fuji
      Varnish, a solvent-based lacquer, or Fuji Coat, a light-cured varnish). Four
      specimens were prepared for each material. They were weighed at hourly intervals
      for 6h, daily for up to 5 days, then weekly thereafter until equilibration.
      RESULTS: Unlike the uncoated specimens, water loss from varnished cements was not
      Fickian, but followed the form: mass loss=A/t+B, where t is time, A and B are
      constants specific to each cement/varnish combination. A varied from 1.22 to 1.30
      (mean 1.26, standard deviation 0.04), whereas B varied from 1.54 to 2.09 (mean 
      1.83, standard deviation 0.29). At equilibrium, varnished specimens lost much
      less water than unvarnished ones (p>0.01) but there was no significant difference
      between the solvent-based and the light-cured varnishes. SIGNIFICANCE: Varnishes
      protect immature glass-ionomer cements from drying out by altering the mechanism
      of water loss. This slows the rate of drying but does not necessarily change the
      total amount of water retained. It confirms that, in clinical use, glass-ionomer
      restoratives should be varnished to allow them to mature satisfactorily.

PMID- 17459467
TI  - Stramonita haemastoma as a bioindicator for organotin contamination in coastal
      environments.
AB  - Stramonita haemastoma was investigated as a suitable bioindicator of TBT and TPhT
      contamination in the tropical Atlantic Ocean by: 1. Imposex induction in healthy
      females after inoculation with TBT and TPhT in the laboratory; and 2. Determining
      incidence of imposex in S. haemastoma collected from areas with various levels of
      tributyltin (TBT) and triphenyltin (TPhT) and determining the concentrations of
      these chemical in its tissues and that of its prey, the mussell Perna pernas.
      Imposex intensities and organotin concentrations in tissues showed good
      correlation, indicating S. haemastoma as a reliable bioindicator of TBT and TPhT
      contamination in coastal waters. Body burden threshold of TBT and TPhT for
      imposex induction was estimated to be 10-20 ng g(-1).

PMID- 17459468
TI  - Water-soluble chitosan-based antisense oligodeoxynucleotide of interleukin-5 for
      treatment of allergic rhinitis.
AB  - Interleukin (IL)-5 produced by allergen specific T cells is a major cytokine in
      the allergic inflammation such as allergic rhinitis (AR). To inhibit the
      production of IL-5, water-soluble chitosan (WSC)-based IL-5 antisense
      oligodeoxynucleotide (AS-ODN) complex was generated. WSC, a biocompatible
      cationic polymer, was used as a non-viral vector for the improvement of stability
      and transfection efficiency. After condensation IL-5 AS-ODN with WSC, the size,
      morphology and zeta potential analysis of IL-5 AS-ODN/WSC complexes were
      performed. The protective effect of complex was also observed against the
      enzymatic degradation. In vitro transfection efficiency into H1299 epithelial
      cells was investigated by flow cytometer and inhibition effect of IL-5 levels was
      also evaluated in D10.G4.1 cells. In the murine model with AR, the IL-5 and IgE
      levels closely related to the allergic inflammation were significantly reduced
      after the intranasal administration of IL-5 AS-ODN/WSC complexes. Based on these
      results, the condensation with WSC improved the physicochemical stability and
      transfection efficiency of IL-5 AS-ODN/WSC complex. Our results suggest that AS
      therapy using IL-5 AS-ODN/WSC complex can be an effective strategy in regulating
      IL-5 and may be applied to the treatment of allergic disorder related to IL-5.

PMID- 17459469
TI  - Glycoconjugated peptide dendrimers-based nanoparticulate system for the delivery
      of chloroquine phosphate.
AB  - Dendrimers consisting of different molecules of metabolic pathways such as amino
      acids can greatly reduce the toxicity associated with amine-terminated dendrimers
      e.g. polyamidoamine (PAMAM) and polypropylene imine (PPI) dendrimers. In the
      present study, poly-L-lysine dendrimers having polyethyleneglycol (PEG-1000) as
      core, were synthesized upto fourth generation. Dendrimers were synthesized by
      alternating protection and deprotection steps of L-lysine by di-BOC (di-tertiary
      butyl pyrocarbonate) till the formation of 4.0 G peptide dendrimer took place. D
      galactose was selected as model sugar for peripheral conjugation (coating) of
      these peptide dendrimer. The complete formation of uncoated and galactose-coated
      poly-L-lysine dendrimers was characterized by transmission electron microscopy
      (TEM), IR, NMR and MALDI TOF mass spectroscopic studies. Chloroquine phosphate
      (CP)-loaded uncoated and coated dendrimers were evaluated for in vitro drug
      release rate, hemolytic toxicity and stability studies. Ex vivo cellular uptake
      studies of uncoated and coated drug dendrimer formulations in macrophages
      revealed almost 5 times reduced phagocytosis due to galactose coating (p<0.0001).
      In vitro-in vivo release behavior indicated possibilities of galactose-coated
      drug dendrimers formulation in controlled drug delivery of CP. Galactose coated
      formulations drastically reduced hemolytic toxicity compared to uncoated poly-L
      lysine formulation as well as plain drug. Hematological data suggests that
      galactose-coated formulations are less immunogenic compared to uncoated
      formulations. Finally, it can be concluded that galactose-coated polylysine
      dendrimers can be utilized for controlled delivery of CP more safely compared to
      its uncoated formulation both in vitro and in vivo.

PMID- 17459470
TI  - Controlling cell adhesion to surfaces via associating bioactive triblock
      proteins.
AB  - A surface functionalization strategy that produces substrates with well
      controlled ligand density is critical to investigating the role of cell-substrate
      interactions in regulating cell adhesion, viability, migration, proliferation and
      differentiation. Towards this end, we have designed and synthesized a triblock
      protein, CRC, comprising a polyelectrolyte domain flanked by two amphiphilic
      leucine zipper domains. The amphiphilic end domains of CRC adsorb onto surfaces
      and preferentially associate into trimeric aggregates, forming a hydrogel coating
      layer. Under serum-free conditions, the CRC coating was found to render both 2D
      substrates and 3D scaffolds non-adhesive to cells. A RGDS sequence was inserted
      in the middle domain of CRC (generating the protein CRC-RGDS) and found to
      introduce cell-binding activity. Incorporation of the RGDS sequence did not
      significantly impact the surface activity of CRC, allowing us to titrate the RGDS
      surface density simply by adjusting the relative ratios of the two proteins.
      Ligand density dependent cell-substrate interactions were demonstrated in human
      foreskin fibroblasts, human umbilical vein endothelial cells, and rat neural stem
      cells. The versatility to functionalize a range of different substrate surfaces,
      combined with the ease of controlling surface ligand density, makes these
      triblock proteins an attractive tool for developing cell-specific surface
      coatings with tailored biofunctional attributes.

PMID- 17459471
TI  - Temporal changes in the expression of some neurotrophins in spinal cord
      transected adult rats.
AB  - Functional recovery of neurons in the spinal cord after physical injury is
      essentially abortive in clinical cases. As neurotrophins had been reported to be
      responsible, at least partially, for the lesion-induced recovery of spinal cord,
      it is not surprising that they have become the focus of numerous studies. Studies
      on endogenous neurotrophins, especially the three more important ones, nerve
      growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3
      (NT-3) in injured spinal cord might provide some important clues in clinical
      treatment. Here we investigate the immunohistological expression of the above
      three factors at lower thoracic levels of the spinal cord as well as changes in
      the motor functions of the adult rat hindlimbs after cord transection. The
      injured rats were allowed to survive 3, 7, 14 and 21 days post operation (dpo).
      Flaccid paralysis was seen at 3 dpo following cord transection, however, hindlimb
      function showed partial recovery from 7 dpo to 21 dpo. The numbers of NGF, BDNF
      and NT-3 immunopositive neurons and their optical densities all increased in the
      lesion-induced cord. The immuno-expression of NGF and BDNF peaked at 7 dpo, while
      that of NT-3 peaked at 7 dpo and remained so at least up to 14 dpo. These results
      suggested that neurotrophins might play essential roles in functional recovery of
      after spinal cord injury, but the time points for the expression of the three
      factors differed somewhat.

PMID- 17459472
TI  - Limited antitumor-effect associated with toxicity of the experimental cytotoxic
      drug cyclopentenyl cytosine in NOD/scid mice with acute lymphoblastic leukemia.
AB  - The experimental cytotoxic drug cyclopentenyl cytosine (CPEC) is a non
      competitive inhibitor of the enzyme cytidine triphosphate (CTP) synthethase. We
      evaluated the in vitro and in vivo antitumor activity of CPEC on human acute
      lymphoblastic leukemia (ALL) cell lines. CPEC displayed anti-leukemic activity
      with IC50 (after 3 days of incubation) ranging from 6 to 15 nM. Subsequently the
      in vivo activity of CPEC against primary human ALL was evaluated in a xenogeneic
      model of human ALL using NOD/scid mice inoculated with primary human ALL cells.
      In the model, only a marginal anti-leukemic activity was observed at 1.5 mg kg(
      1) (5 days per week) and 5 mg kg(-1) (2 days per week), however, this activity
      was associated with severe systemic toxicity. The observed toxicity was not
      specific for the NOD/scid model, as toxicity at comparable treatment intensity
      was also observed in Balb/c mice. In conclusion, although CPEC showed antitumor
      activity against human ALL cells in vitro, its activity in the in vivo human
      leukemia model was only marginal and accompanied by severe toxicity.

PMID- 17459473
TI  - Transitory marrow aplasia during Imatinib therapy in a patient with chronic
      myeloid leukemia.

PMID- 17459474
TI  - Attributing responsibility for child maltreatment when domestic violence is
      present.
AB  - OBJECTIVE: The purpose of this study was to examine factors that influence how
      child welfare workers attribute responsibility for child maltreatment and child
      safety in cases involving domestic violence. METHODS: The study used a factorial
      survey approach, combining elements of survey research with an experimental
      design. Case vignettes were constructed by randomly assigning characteristics to
      vignettes believed to be related to assessments about responsibility for child
      maltreatment. Public child welfare workers were systematically sampled and asked
      to rate vignettes on male and female caregivers' responsibility for child
      maltreatment and concerns for safety. RESULTS: The presence of domestic violence
      significantly affected workers' assessments of the attribution of responsibility
      and concern for child safety, more so than variables related to child
      maltreatment. Responsibility for exposing a child to domestic violence differed
      for males and females, with more factors explaining female responsibility.
      Substance use by either caregiver was significant in attributing responsibility
      for physical harm, not watching the child closely enough, and concern for child
      safety, but not for exposure to domestic violence. CONCLUSIONS: Domestic violence
      appeared to heighten workers' assessments of responsibility for child
      maltreatment and concerns about child safety, taking precedence over the
      characteristics of the child maltreatment itself. Battering tends to work against
      the domestic violence victim in terms of the attribution of responsibility. A
      greater number of factors affect female responsibility for exposing a child to
      domestic violence than male responsibility, even though in every case the male
      was the designated domestic violence batterer.

PMID- 17459475
TI  - Phenotypic and functional characteristics of rat spleen lymphocytes during
      suckling.
AB  - The aim of this study is to characterize the rat spleen lymphoid tissue during
      the suckling period by means of lymphocyte composition and their functionality.
      Lymphocyte phenotype was determined by immunofluorescence and flow cytometry. The
      proliferative ability and the antibody secretion activity were considered as
      functional markers. During the first 2 weeks of life, rat spleen mainly contained
      B cells (CD45RA+ or Igkappa+). In this period, T (TCRalphabeta+CD4+,
      TCRalphabeta+CD8+ and TCRgammadelta+CD8+) and NK/NKT (NKR-P1A+) cell proportions
      were far less than those of adult rats. Moreover, the spleen immune functionality
      proved to be very low. In the second half of the suckling period, CD4+ and CD8+
      cells in the spleen increased in number and proportion, with immature cells
      progressively displaced by phenotypic mature lymphocytes containing CD3,
      TCRalphabeta, CD5 and CD2 molecules on their surface. Additionally, although B
      and T lymphocyte developed their proliferative ability during this period, it was
      not fully developed at weaning.

PMID- 17459477
TI  - An approach to MRI of metabolic disorders in children.
AB  - Inborn errors of metabolism are a difficult group of disorders for the
      neuroradiologist, as there are few good clinical or neuroradiological criteria
      for differentiating them. In this review, a technique of diagnosis by pattern
      recognition, supplemented by metabolic data from proton MR spectroscopy and
      microstructural data, as assessed by diffusion weighted images, is presented.
      Proper use of these neuroimaging tools can be very useful for separating these
      disorders into more manageable groups, and sometimes allows a specific diagnosis
      to be made.

PMID- 17459476
TI  - Development of novel plasmid vectors and a promoter trap system in Francisella
      tularensis compatible with the pFLN10 based plasmids.
AB  - Francisella tularensis is a category A bioterror pathogen which in some cases can
      cause a severe and fatal human infection. Very few virulence factors are known in
      this species due to the difficulty in working with it as well as the lack of
      tools for genetic manipulation. This work describes the construction of a shuttle
      vector that can replicate in Escherichia coli and F. tularensis as well as two
      distinct promoter trap constructs based on the shuttle vector backbone.
      Replication in F. tularensis is based on the promiscuous origin of replication
      from the Staphylococcus aureus plasmid pC194. We demonstrate the novel plasmids
      can coexist with established F. tularensis vectors based on the pFNL10 plasmid,
      the current workhorse of F. tularensis genetics. Our promoter trap can identify
      promoters that are activated during intracellular growth and survival. These new
      vectors provide additional tools for the genetic manipulation of F. tularensis.

PMID- 17459478
TI  - A Tarasoff for Europe? A European Human Rights perspective on the duty to
      protect.
AB  - It has long been recognised by British courts that a psychiatrist can be
      permitted to depart from his/her duty of confidentiality, in order to issue a
      warning where a patient is deemed to present a real and serious threat to other
      parties. Until recently, however, it seemed that s/he would not be bound to give
      such a warning, or to take other steps to protect third parties. The approach
      adopted throughout much of the USA, and famously expounded in the Tarasoff
      judgment, appeared to have no relevance to British law. This article considers
      the possibility that the European Court of Human Rights' ruling in Osman v UK may
      be set to bring about a radical change in this respect, introducing something
      akin to the Tarasoff approach into the UK, and indeed throughout Europe. As well
      as the possible legal basis for such a duty, and the circumstances in which it
      would arise, it will consider how a psychiatrist might reconcile any such duty
      with other, more established, legal and ethical duties.

PMID- 17459479
TI  - Intravitreal triamcinolone plus sequential grid laser versus triamcinolone or
      laser alone for treating diabetic macular edema: six-month outcomes.
AB  - OBJECTIVE: To evaluate the efficacy of sequential intravitreal triamcinolone
      acetonide (TA) injection followed by grid laser photocoagulation for treating
      diabetic macular edema (DME). DESIGN: Prospective, 3-armed, randomized clinical
      trial. PARTICIPANTS: One hundred eleven eyes of 111 patients with DME involving
      the fovea. INTERVENTION: Patients were randomized to grid laser photocoagulation
      (37 eyes), 4 mg of intravitreal TA (38 eyes), or 4 mg of intravitreal TA combined
      with sequential grid laser about 1 month later (36 eyes). MAIN OUTCOME MEASURES:
      Central foveal thickness (CFT) as measured by optical coherence tomography,
      logarithm of the minimum angle of resolution (logMAR) best-corrected visual
      acuity (BCVA), and side effect profiles. The 6-month results are reported.
      RESULTS: All patients completed 6 months' follow-up. Baseline mean (+/- standard
      deviation) CFTs were 385+/-100 microm, 396+/-91 microm, and 424+/-108 microm for
      the laser, intravitreal TA, and combined groups, respectively (P = 0.24). After
      treatment, significant CFT reductions were noted in both the intravitreal TA and
      combined groups at all follow-up visits (P<0.01) but not in the laser group. Mean
      CFT improved significantly to minimums of 267+/-75 microm and 256+/-73 microm for
      the intravitreal TA and combined groups, respectively, but the difference between
      the 3 groups was not significant at 6 months. The standardized change in macular
      thickening at 17 weeks was significantly greater in the combined group versus the
      intravitreal TA group (P = 0.007), suggesting that combined treatment might
      prolong the effects of intravitreal TA. Mean baseline logMAR BCVAs were 0.64+/
      0.37, 0.72+/-0.34, and 0.69+/-0.34 in the laser, intravitreal TA, and combined
      groups, respectively (P = 0.67). Best-corrected visual acuity improved
      significantly at 4 and 9 weeks for the intravitreal TA group but did not change
      significantly in the other 2 groups. No significant difference in BCVA was
      observed between the 3 groups at any time point. CONCLUSIONS: Contrary to the
      results of a recent study, combined treatment of intravitreal TA plus grid laser
      did not yield better CFT reduction or BCVA improvement at 6 months than
      intravitreal TA alone. Grid laser alone was significantly worse than the 2 other
      treatment modalities.

PMID- 17459480
TI  - Comparison of the effects of bimatoprost and a fixed combination of latanoprost
      and timolol on circadian intraocular pressure.
AB  - OBJECTIVE: To compare the effect of bimatoprost and the fixed combination of
      latanoprost and timolol (LTFC) on 24-hour mean intraocular pressure (IOP) after
      patients are switched from a nonfixed combination of latanoprost and timolol.
      DESIGN: Randomized, double-masked, multicenter clinical trial. PARTICIPANTS: Two
      hundred patients with glaucoma or ocular hypertension. METHODS: Included were
      patients who were controlled (IOP < 21 mmHg) on the nonfixed combination of
      latanoprost and timolol for at least 3 months before the baseline visit or
      patients on monotherapy with either latanoprost or timolol who were eligible for
      dual therapy not being fully controlled on monotherapy. The latter group of
      patients underwent a 6-week wash-in phase with the nonfixed combination of
      latanoprost and timolol before baseline IOP determination and study inclusion.
      Supine and sitting position IOPs were recorded at 8 pm, midnight, 5 am, 8 am,
      noon, and 4 pm at baseline, week 6, and week 12 visits. MAIN OUTCOME MEASURE: An
      analysis of covariance model was used for a noninferiority test of the primary
      efficacy variable, with mean area under the 24-hour IOP curve after 12 weeks of
      treatment as response variable and treatment, center, and baseline IOP as
      factors. A secondary analysis was performed on the within-treatment change from
      baseline. RESULTS: Mean baseline IOPs were 16.3+/-3.3 mmHg and 15.5+/-2.9.mmHg in
      the bimatoprost and LTFC groups, respectively. At week 12, mean IOPs were 16.1+/
      2.5 mmHg for the bimatoprost group and 16.3+/-3.7 mmHg for the LTFC group, and no
      significant difference between the 2 treatment groups could be found. As compared
      with baseline, mean IOP increased by 0.3+/-3.6 mmHg during the day and decreased
      by 0.8+/-3.8 mmHg during the night in the bimatoprost group, whereas there were
      increases of 1.43+/-2.6 mmHg and 0.14+/-3.2 mmHg in the LTFC group, respectively.
      CONCLUSIONS: Bimatoprost is not inferior to the LTFC in maintaining IOP at a
      controlled level during a 24-hour period in patients switched from the nonfixed
      combination of latanoprost and timolol.

PMID- 17459481
TI  - Diagnostic accuracy of scanning laser polarimetry with enhanced versus variable
      corneal compensation.
AB  - PURPOSE: To compare the diagnostic accuracy of scanning laser polarimetry (SLP)
      parameters between images taken with enhanced corneal compensation (ECC) and
      those with variable corneal compensation (VCC) and to explore the effect of
      atypical birefringence patterns on this accuracy. DESIGN: Cross-sectional
      observational study. PARTICIPANTS: Forty-one healthy subjects and 92 patients
      with primary open-angle glaucoma. METHODS: Variable corneal compensation and ECC
      images were obtained of 1 eye per subject, selected randomly if both eyes were
      eligible. For both ECC and VCC, the areas under the receiver operating
      characteristic curves (AUROCs) and the sensitivity at a specificity of > or =95%
      were calculated per parameter in all eyes. The analyses were reperformed
      separately in eyes with and without atypical birefringence patterns (ABP) images.
      MAIN OUTCOME MEASURES: The AUROCs and sensitivities at a specificity of > or =95%
      for various SLP parameters in all eyes and in eyes without ABP images. RESULTS:
      The diagnostic accuracy for most standard parameters (temporal-superior-nasal
      inferior-temporal [TSNIT] average, superior average, inferior average, and TSNIT
      standard deviation) in all eyes was statistically significantly higher with ECC
      than with VCC, except for the nerve fiber indicator (NFI). When only eyes without
      ABP were used for the analysis, the diagnostic accuracy of SLP parameters with
      VCC improved, and the differences in diagnostic accuracy between ECC and VCC for
      these parameters lost their statistical significance. CONCLUSIONS: Standard SLP
      parameters (except for the NFI) generally had a higher diagnostic accuracy when
      eyes were imaged with ECC than with VCC because there were fewer ABP images with
      ECC than with VCC. Enhanced corneal compensation therefore may be more reliable
      than VCC for the detection of glaucoma. A future automated classifier, similar to
      the current NFI, may perform better if it is trained on data obtained with ECC.
      Clinically, retinal nerve fiber layer images with marked ABP, acquired with
      either ECC or VCC, should be viewed with caution.

PMID- 17459482
TI  - Outcome of patients with retinoblastoma and postlaminar optic nerve invasion.
AB  - PURPOSE: To evaluate the outcome of patients with retinoblastoma and postlaminar
      optic nerve invasion (PLONI). DESIGN: Retrospective interventional case series.
      PARTICIPANTS: Sixty-one consecutive patients included in 3 successive protocols
      were analyzed. METHODS: Pathologic review was done in each case. Patients were
      stratified into 2 risk groups: the high-risk group included those with
      concomitant full choroidal and/or scleral invasion and were given adjuvant
      chemotherapy. Those without these features were considered low risk and
      chemotherapy was withheld after 1994. MAIN OUTCOME MEASURES: Extraocular relapse
      and survival according to stratification. RESULTS: The probability of event-free
      survival (pEFS) was 0.91 and the probability of overall survival (pOS) was 0.94
      at 5 years. Patients in the high-risk group (n = 22) had pEFS of 0.86. Three had
      extraocular relapse (involving the central nervous system; all died of disease).
      Microscopic scleral invasion was associated to extraocular relapse (P = 0.05).
      Lower risk patients (n = 39) had a pEFS of 0.94 and pOS of 1. Eighteen received
      postenucleation chemotherapy and none relapsed. Twenty-one received no adjuvant
      therapy and 2 had a systemic relapse but were successfully retrieved. Relapsing
      patients had a higher ratio of affected optic nerve (>25% of it overall length; P
      = 0.02). CONCLUSIONS: Patients with PLONI have an excellent outcome with current
      therapy. Risk stratification according to the presence of concomitant choroidal
      and/or scleral invasion may help in the decision of giving adjuvant therapy.

PMID- 17459483
TI  - Intraocular lens calculations after hyperopic refractive surgery.
AB  - PURPOSE: To evaluate the effect of hyperopic refractive surgery on intraocular
      lens (IOL) power calculation, compare published methods of IOL power calculation
      after refractive surgery, evaluate the effect of prerefractive surgery refractive
      error on IOL deviation, and introduce a new alternative formula for IOL
      calculation in patients who have had refractive surgery for hyperopia. DESIGN:
      Retrospective noncomparative case series. PARTICIPANTS: Twenty eyes from 13
      patients who had undergone cataract surgery after previous hyperopic refractive
      surgery. METHODS: Seven different methods of IOL calculation were performed
      retrospectively: clinical history (IOL(hisK)), clinical history method at
      spectacle plane (IOL(hisKs)), vertex (IOL(vertex)), back calculated (IOL(BC)),
      calculation based on average keratometry (IOL(avgK)), calculation based on
      steepest keratometry (IOL(steepK)), and calculation based on the double K formula
      (IOL(doubleK)). Each method's result was compared with an exact IOL (IOL(exact)),
      which would have resulted in emmetropia. Each method was then compared with
      change in spherical equivalent induced by refractive surgery (SE(h)). A paired t
      test was used to determine statistical significance. MAIN OUTCOME MEASURE: Mean
      error in IOL power prediction for each method when compared to IOL(exact).
      RESULTS: When evaluating different methods of IOL calculations, IOL(vertex) was
      the most accurate, with a mean deviation from emmetropia of 0.42+/-1.75 diopters
      (D), followed by IOL(BC) (+0.54+/-1.86 D), IOL(hisK) (+1.56+/-2.35 D), IOL(hisKs)
      (+1.57+/-2.35 D), IOL(steepK) (+1.59+/-2.25 D), IOL(doubleK) (+1.65+/-2.56 D),
      and IOL(avgK) (+2.24+/-2.46 D). There was no statistical difference between
      IOL(vertex), IOL(BC), and IOL(exact). The power of IOL(avgK) would be inaccurate
      by 0.27x+1.53, where x = SE(h). Thus, most patients without the adjustment to
      IOL(avgK) would be left myopic. However, when IOL(avgK) is adjusted with this
      formula, there is no statistical difference to IOL(exact). CONCLUSIONS: For IOL
      power selection in previously hyperopic patients, a predictive formula based only
      on SE(h) and current average keratometry readings was not found to statistically
      differ from IOL(exact). The IOL(vertex) and IOL(BC), which also did not
      statistically differ from IOL(exact), require prerefractive surgery keratometry
      readings that are often not available to the cataract surgeon.

PMID- 17459484
TI  - Regulation and biological activities of the autotaxin-LPA axis.
AB  - Autotaxin (ATX), or nucleotide pyrophosphatase/phosphodiesterase 2 (NPP2), is an
      exo-enzyme originally identified as a tumor cell autocrine motility factor. ATX
      is unique among the NPPs in that it primarily functions as a lysophospholipase D,
      converting lysophosphatidylcholine into the lipid mediator lysophosphatidic acid
      (LPA). LPA acts on specific G protein-coupled receptors to elicit a wide range of
      cellular responses, ranging from cell proliferation and migration to neurite
      remodeling and cytokine production. While LPA signaling has been studied
      extensively over the last decade, we are only now beginning to explore the
      properties and biological importance of ATX as the major LPA-producing
      phospholipase. In this review, we highlight recent advances in our understanding
      of the ATX-LPA axis, giving first an update on LPA action and then focusing on
      ATX, in particular its regulation, its link to cancer and its vital role in
      vascular development.

PMID- 17459485
TI  - Changes in the seasonality of suicides over time in Slovenia, 1971 to 2002.
      Amplitude is only positively related to suicide rates among females.
AB  - BACKGROUND: Changes in the suicide rate within one region over time had been
      hypothesised to correspond to changes in suicide seasonality: a recent
      investigation from Italy confirmed such an assumption. Data from Slovenia were
      investigated to further evaluate the links between suicide rates and seasonal
      amplitude. METHODS: A total of 14325 male suicides and 4350 female suicides
      occurring in Slovenia from 1971 to 2002 were investigated with harmonic spectral
      analysis to extract their monthly seasonal dispersion by eight-year intervals.
      Changes in rate over time were analysed with a test for trend based on regression
      analysis. RESULTS: The suicide rates of both males and females increased over
      time, with an evident peak in the 1987-1994 period and a decrease thereafter.
      Seasonality decreased across time in both sexes; however, no change of the peak
      was observed over time. The amplitude of the major 12-month cycle was slightly
      positively related to suicide rates, but the correlation was only statistically
      significant among females (P=0.0053; males: P=0.22). LIMITATIONS: Data could not
      be analysed according to age, the method of suicide, or the diagnosis
      attributable to the deceased, since this information was not available.
      CONCLUSION: The study confirmed that the seasonal effect on mortality by suicide
      is positively related to suicide rates, so much so that changes in suicide rates
      over time correspond to changes in suicide seasonality, but in Slovenia this
      effect was only evident among females, further pointing towards differences by
      sex in the mechanics leading to suicide.

PMID- 17459486
TI  - Depressive symptomatology and male sexual functions in late life.
AB  - BACKGROUND: We aimed to investigate the association between depressive symptoms
      and various male sexual functions, and to identify which depressive symptoms are
      most predictive of erectile dysfunction (ED). METHODS: This was an analytic cross
      sectional study with 160 sexually active men aged 50 or above recruited from a
      large primary care treatment centre. The 5 domains (erectile function, EF;
      intercourse satisfaction, IS; orgasmic function, OF; sexual desire, SD; overall
      satisfaction, OS) of the International Index of Erectile Function (IIEF-15) were
      used to assess various sexual functions. Depressive symptomatology was measured
      by Geriatric Depression Scale and reconfirmed with General Health Questionnaire.
      RESULTS: The level of depressive symptoms was negatively associated with erectile
      function (p<0.01), orgasmic function (p=0.02), intercourse satisfaction (p=0.04)
      and overall satisfaction (p<0.01), and was independent of age, education and
      number of health conditions, but was not associated with sexual desire (p=0.97).
      Erectile dysfunction was significantly associated with age (OR=1.12; 95% CI 1.05
      1.19; p<0.01) and level of depressive symptoms (OR=1.39; 95% CI 1.05-1.85;
      p=0.02) after multivariate adjustment. In particular, only "low mood" (p=0.03)
      and "worthlessness" (p=0.03) remained positively associated with ED after
      multivariate adjustments. LIMITATIONS: Cross-sectional design cannot demonstrate
      direction of causality. CONCLUSIONS: We are the first to implicate "low mood" and
      "worthlessness" in the association between depressive symptoms and ED, and this
      is the first study to investigate the association in Chinese.

PMID- 17459487
TI  - Absent response to niacin skin patch is specific to schizophrenia and independent
      of smoking.
AB  - This study investigated the differences in niacin skin flush responses between
      patients with schizophrenia, bipolar mania, and normal controls. We applied
      niacin patches of three concentrations (0.001 M, 0.01 M, and 0.1 M) to the skin
      of 61 patients with schizophrenia, 18 patients with bipolar mania, and 40 normal
      controls for 5 min. Flush responses were rated at 5, 10 and 15 min after
      application. Flush responses were significantly different among three groups at
      the concentrations of 0.1 M and 0.01 M at all of the three rating time points.
      The use of nicotine did not have significant influences on the flush responses.
      Absent response was significantly more prevalent in the schizophrenia group than
      in the other two groups, but was not significantly different between the bipolar
      and the control group. The greatest degree of differentiation in flush responses
      among groups occurred at the 0.01 M concentration, and the rating time point of
      10 min with 49.2% of schizophrenic patients but only 7.5% of controls and 11.1%
      of bipolar patients not showing a flush response. The niacin skin test for
      schizophrenia had 49.2% sensitivity and 92.5% specificity compared with controls.
      This study found that absent response to niacin skin patch was specific to
      schizophrenia and independent of smoking status.

PMID- 17459488
TI  - An abbreviated version of the Connor-Davidson Resilience Scale (CD-RISC), the CD
      RISC2: psychometric properties and applications in psychopharmacological trials.
AB  - Resilience may be an important component of the prevention of neuropsychiatric
      disease. Resilience has proved to be quantifiable by scales such as the Connor
      Davidson Resilience Scale (CD-RISC). Here, we introduce a two-item version of
      this scale, the CD-RISC2. We hypothesize that this shortened version of the scale
      has internal consistency, test-retest reliability, convergent validity, and
      divergent validity as well as significant correlation with the full scale.
      Additionally, we hypothesize that the CD-RISC2 can be used to assess
      pharmacological modification of resilience. We test these hypotheses by utilizing
      data from treatment trials of post-traumatic stress disorder, major depression,
      and generalized anxiety disorder with setraline, mirtazapine, fluoxetine,
      paroxetine, venlafaxine XR, and kava as well as data from the general population,
      psychiatric outpatients, and family medicine clinic patients.

PMID- 17459489
TI  - Transmission of antibodies from mother to young: Evolutionary strategies in a
      proteolytic environment.
AB  - Transmission of antibody from mother to young is an essential process. Maternal
      proteins provide both food (if digested) and immune protection (undigested
      antibody) for the offspring. The processes for transfer changed and diversified
      during vertebrate evolution, using receptor-dependent and -independent mechanisms
      pre- and postnatally. Transmission frequently proceeds in a proteolytic
      environment and different mechanisms evolved for the protection of antibody. The
      present review focuses on the relationship of acquisition of passive immunity to
      other physiological processes.

PMID- 17459490
TI  - The effect of adenotonsillectomy on oxygen saturation in children with sleep
      breathing disorders.
AB  - OBJECTIVE: To evaluate the effect of adenotonsillectomy on the oxygen saturation
      measures by nocturnal pulse oximetry in children with sleep breathing disorders
      (SBD). METHODS: A non-controlled clinical trial was performed. Thirty-one
      children with suspected SBD and a clinical indication for adenotonsillectomy were
      recruited. All of them underwent overnight oxygen saturation monitoring before
      and after surgery. RESULTS: Twenty-seven patients completed the study. The mean
      age was 5.2+/-1.8 years. Eighteen (66.7%) were male. The most prevalent symptoms
      were: snoring (100%), respiratory pauses (96.8%), nocturnal mouth breathing
      (96.8%), restless sleep (80%) and drooling (74.1%). Twenty-three children (85.2%)
      presented grade 3 or 4 tonsillar hyperplasia. There was a significant improvement
      in the postoperative oxygen desaturation index (ODI) (0.65; 0.5-1.3) compared
      with the preoperative index (1.63; 1.1-2.4) (p<0.001). CONCLUSION:
      Adenotonsillectomy improved the oxygen saturation measures by nocturnal pulse
      oximetry in children with sleep breathing disorders.

PMID- 17459491
TI  - The attenuation of vaccinia Tian Tan strain by the removal of the viral M1L-K2L
      genes.
AB  - To generate a safe vaccinia Tian Tan (VTT)-based vaccine vector, it is necessary
      to develop a method to attenuate the virus. A modified VTT (MVTT(2-GFP)) was
      constructed by replacing the viral M1L-K2L genes with a GFP gene. In comparison
      to the parental VTT, MVTT(2-GFP) lost its replication capacity in rabbit RK13 and
      human HeLa cell lines. The life cycle of viral replication was blocked at
      different stages in these two cell lines as determined by electron microscope
      examination. MVTT(2-GFP) was less virulent than VTT for 100-fold by measuring
      mouse body weight loss after intranasal viral inoculation and for 340-fold by
      determining the intracranial LD(50) value in mice. The foreign GFP gene was
      stable genetically after 10 rounds of passage in Vero cells. Importantly, MVTT(2
      GFP) elicited both humoral and cell-mediated immune responses to the GFP gene in
      mice. With two intramuscular inoculations of 10(5)PFU virus, the anti-GFP
      antibody reciprocal endpoint titer reached over 700 as determined by an ELISA.
      The number of IFN-gamma secreting T cells reached over 350SFU per million
      splenocytes against a CD8+ T cell-specific epitope of GFP. Collectively, the
      removal of the M1L-K2L genes is a useful method to generate an attenuated
      vaccinia Tian Tan vaccine vector.

PMID- 17459492
TI  - In vitro anti-HIV and -HSV activity and safety of sodium rutin sulfate as a
      microbicide candidate.
AB  - Sodium rutin sulfate (SRS) is a sulfated rutin modified from the natural flavonol
      glycoside rutin. Here, we investigated its in vitro anti-HIV and -HSV activities
      and its cytotoxic profile. Fifty percent inhibitory concentration (IC(50)) values
      of SRS against HIV-1 X4 virus IIIB, HIV-1 R5 isolates Ada-M and Ba-L were 2.3+/
      0.2, 4.5+/-2.0 and 8.5+/-3.8 microM with a selectivity index (SI) of 563, 575 and
      329, respectively. Its IC(50) against primary R5 HIV-1 isolate from Yunnan
      province in China was 13.1+/-5.5 microM, with a SI of 197. In contrast,
      unsulfated rutin had no activity against any of the HIV-1 isolates tested.
      Further study indicated that SRS blocked viral entry and virus-cell fusion likely
      through interacting with the HIV-1 envelope glycoprotein. SRS also demonstrated
      some activity against human herpes simplex virus (HSV) with an IC(50) of 88.3+/
      0.1 microM and a SI of 30. The 50% cytotoxicity concentration (CC(50)) of SRS was
      >3.0 mM, as determined in human genital ME180, HeLa and primary human foreskin
      fibroblast cells. Minimum inhibitory concentration of SRS for vaginal
      lactobacilli was >3.0 mM. These results collectively indicate that SRS represents
      a novel candidate for anti-HIV-1/HSV microbicide development.

PMID- 17459493
TI  - Habituation enhances auditory perceptual capacity in adult rats.
AB  - We have already demonstrated that pretreatment of adult rats with a 48-h-long
      "repetitive non-reinforced sound exposure (SE)" improves performance in two-sound
      discriminative operant conditioning (sound exposure-modulated discrimination
      [SED]). This three-part study addressed the neural basis of SED by parametrically
      analyzing SED: effects of the SE using various sound signals were compared during
      the performance of a sound-discrimination task. Experiment 1 provided evidence
      that SED was due to the improvement of auditory perceptual capacity rather than
      due to a change in motivation or attention or interference with association
      process. Results of Experiment 2 made it likely that SED took place mainly in
      higher cortical auditory fields, which potentially integrate acoustic information
      beyond the cochleotopy. Results of Experiment 3 favored the idea that SED was
      based on a stimulus-specific decrease rather than a stimulus-specific increase in
      the responsivity of the auditory system. Collectively, it is suggested that
      auditory habituation plays an important role in SED, i.e., a certain form of
      auditory perceptual learning.

PMID- 17459494
TI  - Non-photic phase resetting of Dexras1 deficient mice: a more complicated story.
AB  - Recently, it has been reported that mice deficient for Dexras1 have a diminished
      phase-shifting response to photic stimuli but an enhanced response to non-photic
      stimuli; the latter is of additional interest in that mice generally show
      relatively weak and unreliable responses to non-photic events. Therefore, in
      situations in which both photic and non-photic stimuli are present, control of
      circadian rhythms, relative to wild-types, should tip toward non-photic stimuli
      in Dexras1(-/-) mice. However, we detected no differences in an experiment in
      which photic and non-photic entraining agents were presented 180 degrees out of
      phase, i.e. were in conflict with each other. Furthermore, Dexras1(-/-) and wild
      type mice did not differ in non-photic phase shifting to a pulse of confinement
      in a novel running wheel. Suppression of locomotion by light (masking effect) did
      not differ between the genotypes, indicating that the photoreceptor input to the
      non-image forming system is intact. The circadian phenotype of Dexras1(-/-) mice
      appears to be more complicated than previously thought.

PMID- 17459495
TI  - Molecular cloning, expression, biochemical characteristics, and biomarker
      potential of theta class glutathione S-transferase (GST-T) from the polychaete
      Neanthes succinea.
AB  - We cloned and sequenced the full-length cDNA of a theta class glutathione S
      transferase (GST-T) from the polychaete Neanthes succinea. The open reading frame
      of N. succinea GST-T cDNA was 678bp and encoded 226 amino acid residues. We
      generated recombinant N. succinea GST-T by expression in transformed Escherichia
      coli and studied the kinetic properties as well as the effects of inhibitors, pH,
      and temperature on N. succinea GST-T. GST-T expression was studied using real
      time RT-PCR in response to exposure to the model oxidative stress-inducing agent,
      CuCl(2). Copper induced a concentration-dependant increase in the expression of
      GST-T. Moreover, polychaetes collected from a heavily contaminated lake near an
      industrial complex showed significantly higher levels of GST-T expression.
      Interestingly, the site-collected polychaetes with the highest GST-T mRNA
      expression levels also showed the highest metallothioneins levels. These results
      suggest that GST-T in polychaetes may have an antioxidant role and that N.
      succinea GST-T expression may be a useful biomarker for exposure to environmental
      contaminants such as copper. Our findings provide a better understanding of the
      biochemical characteristics of N. succinea GST-T, and elucidate the potential
      role of GST-T in heavy metal-induced oxidative stress and as a biomarker for
      environmental contamination.

PMID- 17459496
TI  - Nuclear import of human sexual regulator DMRT1 is mediated by importin-beta.
AB  - Human DMRT1 (Doublesex-Mab3-Related Transcription factor 1) encodes a male
      specific transcriptional regulator with a conserved zinc-finger-like DNA-binding
      domain, so called DM domain, which is similar to male sexual regulatory genes
      doublesex of Drosophila and mab-3 of Caenorhabditis elegans. As a key
      transcription factor critical to sex determination and differentiation, however,
      human DMRT1 nuclear import mechanism remains unknown. We have identified a
      functional nuclear localization signal (NLS) located between the two intertwined
      zinc-binding sites of the DM domain. Site-directed mutagenesis indicates that K92
      and R93 within the DM domain are critical for DMRT1 nuclear localization.
      Analysis of deletion mutants shows that importin-beta1 binds directly to DMRT1
      via the DM domain, mediating its nuclear import. Co-immunoprecipitation analysis
      confirms the interaction of mouse Dmrt1 in Sertoli cells with importin-beta1 in
      vivo. In addition, in vitro docking or nuclear transport assay in digitonin
      permeabilized cells shows that DMRT1 is docked at the nuclear pore complex (NPC)
      or accumulated in the nucleus when importin-beta1, but not importin-alpha1 added.
      Furthermore, transduction of anti-importin-beta1 antibody into live Sertoli cells
      effectively inhibits DMRT1 nuclear import. These results suggest that zinc finger
      domain of DMRT1 functions as a nuclear localization signal and DMRT1 is
      transported into the nucleus in an importinbeta1-mediated manner. Thus, effective
      nuclear import of DMRT1 and its interaction with importin-beta1 insure the
      nuclear retention of the DMRT1 and further exertion of its influence on
      downstream targets in the cascade of sexual development.

PMID- 17459497
TI  - Subacute stent thrombosis happening at discharge.
AB  - We present the two cases of men who were admitted to our hospital with effort
      angina and three vessels lesions. The symptoms were alleviated after three
      sirolimus-eluting stents implantation. But on the scheduled discharge day when
      the patients were on therapy of clopidogrel, in combination with aspirin or
      anticogulation, subacute stent thrombosis (SST) happened and led to patients'
      death.

PMID- 17459498
TI  - Patent foramen ovale in high-altitude pulmonary edema: a vicious cycle.

PMID- 17459499
TI  - Coronary artery bypass surgery or percutaneous coronary intervention after
      fibrinolysis: a critical reappraisal.

PMID- 17459500
TI  - Variant form of tako-tsubo cardiomyopathy.
AB  - We report a female case of variant form of tako-tsubo cardiomyopathy in which
      wall motion of the distal segment was preserved. In the current case, left
      ventriculography showed akinesia of the mid portion and normokinesia of the
      distal and basal portions of the left ventricular chamber. ST-segment elevation
      was obvious in leads V1-3 rather than in leads V4-6. Because ST-segment elevation
      is absent in left precordial leads, cardiologists should take care not to fail to
      diagnose variant form of tako-tsubo cardiomyopathy.

PMID- 17459501
TI  - Long-term follow-up after percutaneous coronary intervention in patients with
      systemic lupus erythematosus.

PMID- 17459502
TI  - Projecting long term medical spending growth.
AB  - We present a dynamic general equilibrium model of the U.S. economy and the
      medical sector in which the adoption of new medical treatments is endogenous and
      the demand for medical services is conditional on the state of technology. We use
      this model to prepare 75-year medical spending forecasts and a projection of the
      Medicare actuarial balance, and we compare our results to those obtained from a
      method that has been used by government actuaries. Our baseline forecast predicts
      slower health spending growth in the long run and a lower Medicare actuarial
      deficit relative to the previous projection methodology.

PMID- 17459503
TI  - Enhanced frequency of Beauveria bassiana blastospore transformation by
      restriction enzyme-mediated integration and electroporation.
AB  - The techniques of restriction enzyme-mediated integration (REMI) and
      electroporation (EP) were applied for the first time to improving the blastospore
      transformation of fungal biocontrol agent Beauveria bassiana for higher
      frequency. The blastospores from < or =24 h incubation in glucose-mineral medium
      after shaking conidia for 48 h in Subouraud dextrose broth were found most
      competent for integrating 1 microg plasmid DNA vectoring the phosphinothricin
      (PPT) resistance gene bar in 360 microL reaction system containing 100 U HindIII
      or XbaI. Such blastospores were also most suitable for EP transformation at the
      optimized field strength of 10 kV cm(-1). The optimized REMI and EP generated
      averagely 39 and 53 transformants microg(-1) plasmid DNA whereas polyethylene
      glycol (PEG) integration yielded only 22. All transformants grew well on Czapek's
      agar containing 400 microg PPT mL(-1) after three rounds of cultivation on the
      same agar excluding PPT but their parental strain showed no resistance. The
      target gene inserted into the genomes of 10 transformants randomly taken from
      REMI or EP transformation was consistently detected by both PCR and Southern
      blotting. Compared to the PEG integration, REMI and EP enhanced the frequency of
      the blastospore transformation by 73 and 137%, respectively.

PMID- 17459504
TI  - Brain oscillations are highly influenced by gender differences.
AB  - There are few studies describing gender differences in event related oscillations
      (EROs). In the present report we demonstrate that gender differences are apparent
      in EROs even during simple visual stimulation, possibly activating very basic
      sensory networks. The data of 32 (16 males) healthy subjects were recorded from
      thirteen different scalp locations (F(3), F(4), C(z), C(3), C(4), T(3), T(4),
      T(5), T(6), P(3), P(4), O(1), O(2)). Analysis was performed in the delta (0.5-3.5
      Hz), theta (5-8.5 Hz), alpha (9-13 Hz), beta (15-24 Hz), and gamma (28-48 Hz)
      frequency ranges. The results showed that the maximum peak-to-peak delta response
      amplitudes for women were significantly higher than for men over occipital,
      parietal, central and temporal electrode locations. There were also
      differentiations in the beta and gamma oscillatory responses. These gender
      differences were most pronounced over the electrode site O(2), that is, over
      primary visual areas. It is suggested that this study might serve as a standard
      to investigate gender differences in electrophysiology.

PMID- 17459505
TI  - Shelf-life of minimally processed cabbage treated with neutral electrolysed
      oxidising water and stored under equilibrium modified atmosphere.
AB  - Minimally processed vegetables (MPV) have a short shelf-life. Neutral
      electrolysed oxidising water (NEW) is a novel decontamination method. The
      objective of this study was to test the potential of NEW to extend the shelf-life
      of a MPV, namely shredded cabbage. Samples of shredded cabbage were immersed in
      NEW containing 40 mg/L of free chlorine or tap water (control) up to 5 min, and
      then stored under equilibrium modified atmosphere at 4 degrees C and 7 degrees C.
      Proliferation of aerobic mesophilic bacteria, psychrotrophic bacteria, lactic
      acid bacteria and yeasts were studied during the shelf-life. Also pH and
      sensorial quality of the samples as well as O(2) and CO(2) composition of the
      headspace of the bags was evaluated. From the microbial groups, only
      psychrotrophic counts decreased significantly (P<0.05) due to the effect of NEW,
      but the counts in treated samples and controls were similar after 3 days of
      storage at 4 degrees C and 7 degrees C. Packaging configurations kept O(2)
      concentration around 5% and prevented CO(2) accumulation. pH increased from 6.1
      6.2 to 6.4 during the shelf-life. No microbial parameter reached unacceptable
      counts after 14 days at 4 degrees C and 8 days of storage at 7 degrees C. The
      shelf-life of controls stored at 4 degrees C was limited to 9 days by overall
      visual quality (OVQ), while samples treated with NEW remained acceptable during
      the 14 days of the experiment. The shelf-life of controls stored at 7 degrees C
      was limited to 6 days by OVQ and browning, while that of samples treated with NEW
      were limited to 9 days by OVQ, browning and dryness. According to these results,
      a shelf-life extension of at least 5 days and 3 days in samples stored
      respectively at 4 degrees C and 7 degrees C can be achieved by treating shredded
      cabbage with NEW. NEW seems to be a promising method to prolong the shelf-life of
      MPV.

PMID- 17459506
TI  - Presence of hepatitis E virus in a naturally infected swine herd from nursery to
      slaughter.
AB  - Hepatitis E virus has recently been recognized as having zoonotic potential and
      could be transmitted from pig to human. Pigs are identified as a potential animal
      reservoir and HEV is highly prevalent in the swine population around the world.
      In this study, the presence of HEV was investigated in 51 subjects reared on a
      simulated commercial farm setting from the age of 2 weeks up to slaughter.
      Samples were collected on four occasions: at 2, 8, and 18 weeks and between 22-29
      weeks of age. Anti-HEV IgG in plasma samples, presence of HEV RNA in plasma
      samples and feces were monitored. At 2 weeks of age, HEV RNA was detected in
      feces of 6 subjects (11.8%) but not in their plasma. At 8 weeks, HEV was detected
      in feces of 27 subjects (52.9%) and in plasma of one subject. At 18 weeks, HEV
      was detected in feces of 44 subjects (86.2%) and in plasma of 24 subjects
      (47.1%). At slaughter time (22-29 weeks), HEV was present in plasma of 6 subjects
      (11.8%) and in stools of 21 subjects (41.2%). Spread of the virus inside the
      population was evaluated by comparison of means (paired t-test, P<0.05) of anti
      HEV IgG ELISA results from the 4 bleedings. Significant differences were noted
      between the results of populations at 8 and 18 weeks and also between 18 and 22
      to 29 weeks indicating an immune response to the virus. Based on the comparison
      of a 304 nucleotides sequence of the 5' ORF 2 gene, all amplified fragments
      clustered in genotype 3a.

PMID- 17459507
TI  - A novel simulation model for stem cells differentiation.
AB  - A novel mathematical model to simulate mesenchymal stem cells differentiation
      into specialized cells is proposed. The model is based upon material balances for
      extracellular matrix compounds, growth factors and nutrients coupled with a mass
      structured population balance describing cell growth, proliferation and
      differentiation. The proposed model is written in a general form and it may be
      used to simulate a generic cell differentiation pathway occurring in vivo or
      during in vitro cultivation when specific growth factors are used. Literature
      experimental data concerning the differentiation of mesenchymal stem cells into
      chondrocytes in terms of total DNA and glycosaminoglycan content are successfully
      compared with model results, thus demonstrating the validity of the proposed
      model as well as its predictive capability. A further test of the model
      capability is performed for the case of in vivo fracture healing during which
      mesenchymal stem cells differentiate into chondrocytes and osteoblasts.
      Considerations about the extension of the proposed model to different pathologies
      beside fracture healing are reported. Finally, sensitivity analysis of model
      parameters is also performed in order to clarify what mechanisms most strongly
      influence differentiation and the distribution of cell types.

PMID- 17459508
TI  - Insulin as a T cell antigen in type 1 diabetes supported by the evidence from the
      insulin knockout NOD mice.
AB  - Rodents have two functional preproinsulin genes named insulin 1 and insulin 2 on
      different chromosome and have two amino acid differences in insulin B chain. We
      have established insulin 1 or insulin 2 knockout (KO) non-obese diabetic (NOD)
      colonies in the animal institute of Kobe University and evaluated anti-insulin
      autoimmunity. Similar to the previous report, insulin 1-KO provides strong
      protection from insulitis (islet-infiltration of mononuclear cells) and diabetes,
      whereas the insulin 2-KO markedly accelerated insulitis and development of
      diabetes even at further backcross breeding with NOD/Shi/Kbe mice (P<0.0001).
      Expression of serum anti-insulin autoantibodies (IAA) was enhanced in insulin 2
      KO mice at a time between 10 and 15 weeks of age (P<0.005) while the expression
      of insulin 1-KO NOD mice was rather reduced. Furthermore, T cell reactivity in
      splenocytes of insulin 2-KO NOD mice to insulin 1 B:9-23 peptide was increased
      (P<0.05), suggesting that expanding insulin-reactive T cells may contribute to
      the acceleration of diabetes in insulin 2-KO mice. Based on those observations,
      we hypothesize that insulin 1 is a crucial T cell antigen in murine autoimmune
      diabetes and modification of anti-insulin autoimmunity can be applicable to
      antigen-based therapy for human type 1 diabetic patients.

PMID- 17459509
TI  - Comparison of the alteration of the concentration of C-peptide in 24-h urine
      according to the combination patterns of hypoglycemic agents in type 2 diabetes
      patients.
AB  - AIMS: Urinary C-peptide (UCP) has been considered as a simple method for
      monitoring beta-cell function in diabetic patients clinically. The aim of the
      study is to compare the changes of 24-h urinary C-peptide levels according to
      subgroups divided by therapeutic agents for subjects with type 2 diabetes.
      METHODS: In 206 participants, under treatment for type 2 diabetes, 24-h urinary C
      peptide levels were assessed yearly for 3 years. All participants were subdivided
      into four groups according to the therapeutic agents. Changes for the measured
      values during the follow-up were compared between groups. RESULTS: Mean HbA1C was
      7.1% and mean 24-h UCP was 61.7 microg/24h and mean duration of diabetes was 8.7
      years in all subjects at baseline. Mean 24-h UCP levels increased significantly
      from a baseline to at 36 months in the insulin sensitizers (IS) only group, in
      the IS plus sulfonylurea combination group and in IS plus insulin combination
      group (p<0.001), whereas in the sulfonylurea only group, we could not find
      statistically significant changes (p=0.152). Treatment with only IS significantly
      reduced fasting plasma glucose (FPG) and HbA1C level (p=0.045, p<0.001).
      Differences between baseline and last 24-h UCP were significantly different
      between-groups and this difference was more significant after adjustment in FPG,
      HbA1C, and the duration of diabetes (p=0.024). Especially, IS plus sulfonylurea
      combination group resulted in greatest increase of 24-h UCP (DeltaC-peptide=51.19
      microg/24h). CONCLUSIONS: This study suggested that IS, in mono- or in
      combination, significantly improved pancreatic beta-cell function, especially
      when combined with sulfonylurea as evidenced by the increase of 24-h UCP.

PMID- 17459510
TI  - Clinical characteristics of Korean type 2 diabetic patients in 2005.
AB  - Korean type 2 diabetics differ from Western diabetics in showing non-obese but
      centrally obese anthropometry and relatively more insulin secretory defects than
      insulin resistance. We assessed insulin secretion based on fasting serum C
      peptide level and insulin resistance using the short insulin tolerance test
      (Kitt; rate constant for plasma glucose disappearance) in 1601 type 2 diabetic
      Korean patients (831 men and 770 women). Insulin secretory defects were
      catergorized as severe (C-peptide<1.10 ng/ml), moderate (C-peptide 1.10-1.69
      ng/ml), and mild to non-secretory defect (C-peptide> or=1.70 ng/ml). Groups with
      a Kitt value of less than 2.5%/min were considered insulin-resistant, while those
      with a Kitt value > or =2.5%/min were considered insulin-sensitive. Overall,
      42.5% of patients had a BMI>or =25.0 kg/m(2), and 70.2% had a BMI> or =23.0
      kg/m(2); 45.2% (41.7% of men and 58.3% of women) were abdominally obese (waist>
      or =90 cm in men and 80 cm in women); mean fasting serum C-peptide level was
      1.93+/-0.90 ng/ml, and the mean Kitt value was 2.03+/-0.96%/min. Accordingly, 13,
      33, and 54% of patients showed a severe, moderate, and mild to non-secretory
      defect, respectively; 70.6% were insulin-resistant; and 29.4% were insulin
      sensitive. Obese type 2 diabetes is recently increasing in Korea, indicating a
      shift from insulin secretory defects to insulin resistance.

PMID- 17459511
TI  - Critical flicker frequency: diagnostic tool for minimal hepatic encephalopathy.
AB  - BACKGROUND/AIMS: Minimal hepatic encephalopathy (MHE) is associated with poorer
      quality of life and increased work disability. Diagnosis requires cumbersome
      psychometric and neurophysiological tests. We evaluated critical flicker
      frequency (CFF) to diagnose MHE. METHODS: 156 cirrhotic patients (age 41+/-12.5
      yr) without overt encephalopathy (Child A 63, Child B 56, Child C 37) were
      evaluated by psychometric (number connection tests A, B or figure connection
      tests A, B), P300 auditory event related potential (ERP) and CFF. MHE was
      diagnosed by abnormal psychometric and/or P300 auditory event related potential.
      RESULTS: Prevalence of MHE was 53% with 27 (43%) in Child's A, 33 (59%) in
      Child's B and 23 (62%) in Child's C cirrhosis (p=NS). Of 83 patients, 72 (87%)
      had abnormal psychometry, 64 (77%) had abnormal P300 auditory event related
      potential (ERP) (380.6+/-28.8 ms) and in 66 (80%) CFF was below 39 Hz. 60 (83%)
      patients with abnormal psychometry and 51 (80%) with abnormal P300 auditory event
      related potential had CFF below 39 Hz. CFF sensitivity (96%), specificity (77%)
      and positive predictive value (68%), negative predictive value (98%) and
      diagnosis accuracy was 83.3% when compared to patients with both abnormal
      psychometry and P300ERP. CONCLUSIONS: Critical flicker frequency is a simple,
      reliable and accurate test without any age or literacy dependence for the
      diagnosis of MHE.

PMID- 17459512
TI  - Enhanced vasoconstrictor prostanoid production by sinusoidal endothelial cells
      increases portal perfusion pressure in cirrhotic rat livers.
AB  - BACKGROUND/AIMS: Cyclooxygenase-1 (COX-1) is overexpressed in sinusoidal
      endothelial cells (SEC) of cirrhotic rat livers, and through an enhanced
      production of vasoconstrictor prostanoids contributes to increase intrahepatic
      resistance. Our study was aimed at investigating the role of enhanced AA
      bioavailability modulating the hepatic vascular tone of cirrhotic livers and
      identifying which prostanoid is involved. METHODS: SEC isolated from control and
      cirrhotic rat livers were incubated with AA, methoxamine or vehicle. TXA(2) was
      quantified. In addition, portal perfusion pressure (PP) response curves to AA
      were performed in rat livers pre-incubated with vehicle, SC-560 (COX-1
      inhibitor), Furegrelate (inhibitor of TXA(2) synthesis) and SQ-29548
      (PGH(2)/TXA(2) receptor blocker). cPLA2 activity was determined in control and
      cirrhotic livers. RESULTS: AA and methoxamine incubation promoted a significant
      increase in TXA(2) release by Cirrhotic-SEC, but not in Control-SEC. AA produced
      a dose-dependent increase in the PP, associated with increased TXA(2) release.
      These responses were significantly greater in cirrhotic livers. COX-1 inhibition
      and PGH(2)/TXA(2) receptor blockade, but not TXA(2) synthase inhibition, markedly
      attenuated the PP response to AA of cirrhotic livers. Additionally, cirrhotic
      livers exhibited significantly increased cPLA2 activity. CONCLUSIONS: An enhanced
      production of vasoconstrictor prostanoids, probably PGH(2), by SEC contributes to
      increase vascular tone of cirrhotic livers.

PMID- 17459513
TI  - Diurnal variation and dispersion in QT interval in cirrhosis: relation to
      haemodynamic changes.
AB  - BACKGROUND/AIMS: A long QT(C) interval has been described in a substantial
      fraction of patients with cirrhosis, but information on QT variation and
      dispersion is sparse. The aim was to determine QT variation with time and QT
      dispersion (QT(disp)). METHODS: The study population comprised 23 patients with
      cirrhosis, undergoing a haemodynamic investigation. 24-h 12 lead Holter
      monitoring provided information on QT and heart rate variability. RESULTS: Mean
      QT(C) was above upper normal limit (440 ms(1/2)) in eleven patients (47%) and
      significantly higher than in controls (441 vs 400 ms(1/2), p<0.01). The minimum
      value of QT(C) (but not the maximum value) showed a significant diurnal variation
      both in cirrhosis and controls. QT(disp) in cirrhosis and controls was similar
      (33 vs 36 ms, ns), but related to indicators of liver dysfunction, central
      circulation time, and arterial blood pressure (r=0.44-0.58, p=0.03-0.001). No
      diurnal variation of QT(disp) was found in cirrhosis. Heart rate variability was
      reduced with a significant relation to central hypovolaemia (r=0.55, p=0.01).
      CONCLUSIONS: Twenty-four hours QT(C) is prolonged in a substantial fraction of
      patients with cirrhosis, but with normal diurnal variation. The combination of
      long QT(C) and normal QT(disp) suggests delayed myocyte repolarisation on the
      cellular level, rather than temporal and spatial heterogeneity in the myocardial
      wall.

PMID- 17459514
TI  - Hypoadiponectinemia accelerates hepatic tumor formation in a nonalcoholic
      steatohepatitis mouse model.
AB  - BACKGROUND/AIMS: Adipose tissue produces a number of adipocytokines, including
      adiponectin, leptin, and tumor necrosis factor-alpha. Obesity, which is
      associated with low plasma adiponectin levels, is an independent risk factor for
      various liver diseases including nonalcoholic steatohepatitis (NASH). The aim of
      this study was to examine the effects of adiponectin on the progression of NASH
      to cirrhosis and tumor formation using adiponectin-knockout (KO) mice. METHODS:
      Using a choline-deficient L-amino acid-defined (CDAA) diet-induced mouse NASH
      model, liver histology and oxidative stress markers were investigated in KO and
      wild-type (WT) mice. RESULTS: Hepatic steatosis was enhanced to a greater extent
      in KO mice, compared to WT mice after a 1-week CDAA diet. After 24 weeks, 6 out
      of 14 KO mice developed liver cirrhosis and hepatic tumors, whereas the 15 WT
      mice showed only simple steatosis. In KO mice, hepatic cytochrome P450 2E1 levels
      were upregulated, and markers of oxidative stress (thiobarbituric acid reactive
      substances, 8-hydroxydeoxyguanosine-positive cells) were significantly increased
      compared with WT mice. CONCLUSIONS: Our results indicate that lack of adiponectin
      enhances the progression of hepatic steatosis, fibrosis, and hepatic tumor
      formation in an animal model of NASH. Hypoadiponectinemia in obesity could be a
      risk factor for NASH-related hepatic tumor formation.

PMID- 17459515
TI  - A model-based method for flow limitation analysis in the heterogeneous human
      lung.
AB  - Flow limitation in the airways is a fundamental process constituting the maximal
      expiratory flow-volume curve. Its location is referred to as the choke point. In
      this work, expressions enabling the calculation of critical flows in the case of
      wave-speed, turbulent or viscous limitation were derived. Then a computational
      model for the forced expiration from the heterogeneous lung was used to analyse
      the regime and degree of flow limitation as well as movement and arrangement of
      the choke points. The conclusion is that flow limitation begins at similar time
      in every branch of the bronchial tree developing a parallel arrangement of the
      choke points. A serial configuration of flow-limiting sites is possible for short
      time periods in the case of increased airway heterogeneity. The most probable
      locations of choke points are the regions of airway junctions. The wave-speed
      mechanism is responsible for flow choking over most of vital capacity and viscous
      dissipation of pressure for the last part of the test. Turbulent dissipation,
      however, may play a significant role as a supporting factor in transition between
      wave-speed and viscous flow limitation.

PMID- 17459516
TI  - Tools for computational processing of LC-MS datasets: a user's perspective.
AB  - Liquid chromatography-mass spectrometry (LC-MS) profiling of clinical samples for
      quantifying absolute ion abundances of peptides and proteins has emerged as a
      promising approach. Quantitation of changes in protein abundance of large number
      of samples is challenging and requires automatic processing means. The
      development of data analysis software is laborious and time-consuming.
      Fortunately, freely available tools have been recently introduced, which
      incorporate algorithms for visualization and data processing and allow the user
      to embed external routines for data analysis. A relevant issue related to the
      design and evaluation of such tools concerns usability. Properties such as easy
      access, large datasets management, modularity, integration with other tools, etc,
      are important for performing large-scale integrative data analysis with methods
      and visual techniques from different (possibly integrated) tools. In this paper,
      we consider four freely available tools recently introduced in top international
      journals in order to identify a list of such usability descriptors. We propose 10
      descriptors that can be used both as guidelines when developing new tools and as
      parameters for assessing usability of existing tools. The considered tools show
      satisfactory usability properties, and the most recent tools exhibit improved
      flexibility, indicating a trend towards the design of tools that give the user a
      more central role in the selection, use and integration of methods and tools.

PMID- 17459517
TI  - Computer-assisted predictive formulas expressing survival probability and life
      expectancy in US adults, men and women, 2001.
AB  - The National Center for Health Statistics (NCHS) reported the United States life
      tables, 2001 for US total, male and female populations on the basis of 2001
      mortality statistics, the 2000 decennial census and the data from the Medicare
      program [E. Arias, United State life tables, 2001, Natl. Vital Stat. Rep. 52
      (2004) 1-40]. The life tables show life expectancy, survival and death rate at
      each year between birth and 100 years of age. In this study formulas expressing
      survival probability and life expectancy in US adults, men and women are
      constructed from the data of the NCHS. A model of the 'probacent'-probability
      equation previously published by the author is employed in the study. Analysis of
      the formula-predicted values and the NCHS-reported data indicates that the
      formulas are accurate and reliable with a close agreement. The formula
      representing a generalized lognormal distribution might be useful for biomedical
      investigation, and epidemiological and demographic studies in US adults, men and
      women.

PMID- 17459518
TI  - RNA interference and innate immunity.
AB  - RNA interference is an evolutionarily conserved gene silencing process triggered
      by double-stranded RNAs. Common to all cell types, is the production of 21-24
      nucleotide small interfering RNA (siRNAs), which guide the RNA-induced silencing
      complex (RISC) to identify and cleave target mRNA sequences. Presently, this
      biological breakthrough method has revolutionised gene function studies and holds
      great promise as validating drug targets and treating human diseases. However,
      despite the success that has been achieved by this technology, studies carried in
      human blood cells have revealed that siRNAs could generate bystander effects,
      including the activation of innate immunity and inhibition of unintended target
      genes. Interestingly, 2' uridine-modified siRNAs did not trigger TLR signalling,
      but they totally suppressed immune activation by immunostimulatory siRNAs when
      both molecules where delivered to the same endosomes. This review describes the
      recent advances in understanding the innate immune response to both single and
      double-stranded siRNAs. Also, it highlights the spectrum of molecular strategies
      allowing the design of therapeutic siRNAs with minimal side effects.

PMID- 17459519
TI  - Non-viral siRNA delivery to the lung.
AB  - SiRNAs exert their biological effect by guiding the degradation of their cognate
      mRNA sequence, thereby shutting down the corresponding protein production (gene
      silencing by RNA interference or RNAi). Due to this property, siRNAs are emerging
      as promising therapeutic agents for the treatment of inherited and acquired
      diseases, as well as research tools for the elucidation of gene function in both
      health and disease. Because of their lethality and prevalence, lung diseases have
      attracted particular attention as targets of siRNA-mediated cures. In addition,
      lung is accessible to therapeutic agents via multiple routes, e.g., through the
      nose and the mouth, thus obviating the need for targeting and making it an
      appealing target for RNAi-based therapeutic strategies. The clinical success of
      siRNA-mediated interventions critically depends upon the safety and efficacy of
      the delivery methods and agents. Delivery of siRNAs relevant to lung diseases has
      been attempted through multiple routes and using various carriers in animal
      models. This review focuses on the recent progress in non-viral delivery of
      siRNAs for the treatment of lung diseases, particularly infectious diseases. The
      rapid progress will put siRNA-based therapeutics on fast track to the clinic.

PMID- 17459520
TI  - Age-period-cohort analysis of lung cancer mortality rates in Andalusia, 1975
      2004.
AB  - Our objective is to describe lung cancer mortality trends in Andalusia, Spain,
      during the period 1975-2004 using age-period-cohort analysis (APC). For each
      gender, age-standardised (European Standard Population) mortality rates from lung
      cancer were computed based on the causes of death on the death certificates from
      the official registry of vital statistics in Andalusia. In men, after climbing
      considerably from 1975 to 1994, adjusted lung cancer mortality rates, have been
      declining by 0.8% per year since 1994. For women, the mortality from lung cancer
      was almost constant but tended to increase after 1994 (average annual increase of
      2.1%). Among males, the cohort effect was steadily and appreciably upwards to the
      cohort born around 1905, then levelled off, and declined in the youngest
      generations. An increasing period effect was also observed until 1995. For
      females, cohort values decreased until the cohort born around 1930, then levelled
      off, and increased for women born since 1940. Period effect trend was downward
      until 1990, and upward thereafter. In conclusion, the cohort effect observed for
      women born since 1940 suggests the start of a lung cancer epidemic associated
      with a higher prevalence of smokers in women. The decrease in prevalence of
      smokers among males and the decrease in mortality in younger age groups suggest
      that the trend initiated in 1994 will continue as long as smoking prevalence
      continues to decrease.

PMID- 17459521
TI  - Food intake affects state body image: impact of restrained eating patterns and
      concerns about eating, weight and shape.
AB  - Body image disturbances play a significant role in the development of eating
      disorders. Since body image can vary in diverse contexts, the aim of the present
      experiment was to investigate whether it is affected by recent food intake. Fifty
      seven females without clinically relevant eating disorders were randomly assigned
      to an experimental group (EG, n=28) that consumed a milkshake while watching a
      neutral film and a control group (CG, n=29) that only viewed the movie. Before
      and after the tasks, participants filled in the "Body Image States Scale" and the
      "Mood Questionnaire" and indicated their own "actual", "felt" and "ideal" body
      dimensions with a digital distortion technique based on a photograph of
      themselves. It was shown that after milkshake consumption, state body
      dissatisfaction as well as the discrepancy between "actual-ideal" and "felt
      ideal" body size estimations was higher in the EG than in the CG. Judgements of
      the "actual", "felt" and "ideal" body dimensions and of mood were not affected.
      Further analyses revealed that the effect of milkshake consumption on body image
      and mood was higher the more the participants displayed restrained eating or
      eating, weight and shape concerns in general. Clinical implications are
      discussed.

PMID- 17459522
TI  - Experienced and remembered pleasure for meals: duration neglect but minimal peak,
      end (recency) or primacy effects.
AB  - Rated liking for dishes consumed during a meal was compared with recalled liking
      in two studies using actual meals and one with an imagined meal. The effects on
      memory of the most pleasant dish, the first and last dishes, a rising vs. falling
      hedonic profile, and the time spent eating a dish were evaluated for similarity
      to effects seen in memories of pain. Across the three studies, there was
      consistent evidence for duration neglect (no effect of increased
      duration/exposure of the favorite component), and some weak evidence that
      patterns rising in liking are preferred to those falling in liking. In all three
      studies, there was no evidence for peak, primacy or recency effects. The
      existence of duration neglect implies that, with respect to memories of a meal,
      small portions of a highly favored dish will have roughly the same memorial
      effect as large portions.

PMID- 17459523
TI  - The complex array of bradykinin-related peptides (BRPs) in the peptidome of
      pickerel frog (Rana palustris) skin secretion is the product of transcriptional
      economy.
AB  - Previous peptidomic analyses of the defensive skin secretion from the North
      American pickerel frog, Rana palustris, have established the presence of
      canonical bradykinin and multiple bradykinin-related peptides (BRPs). As a
      consequence of the multiplicity of peptides identified and their diverse primary
      structures, it was speculated that they must represent the products of expression
      of multiple genes. Here, we present unequivocal evidence that the majority of
      BRPs (11/13) identified in skin secretion by the peptidomic approach can be
      generated by differential site-specific protease cleavage from a single common
      precursor of 321 amino acid residues, named skin kininogen 1, whose primary
      structure was deduced from cloned skin secretion-derived cDNA. The organization
      of skin kininogen 1 consists of a hydrophobic signal peptide followed by eight
      non-identical domains each encoding a single copy of either canonical bradykinin
      or a BRP. Two additional splice variants, encoding precursors of 233 (skin
      kininogen 2) or 189 amino acid residues (skin kininogen 3), were also cloned and
      were found to lack BRP-encoding domains 5 and 6 or 4, 5 and 6, respectively.
      Thus, generation of peptidome diversity in amphibian defensive skin secretions
      can be achieved in part by differential protease cleavage of relatively large and
      multiple-encoding domain precursors reflecting a high degree of transcriptional
      economy.

PMID- 17459524
TI  - TNF-alpha acts in the hypothalamus inhibiting food intake and increasing the
      respiratory quotient--effects on leptin and insulin signaling pathways.
AB  - Acting in the hypothalamus, tumor necrosis factor-alpha (TNF-alpha) produces a
      potent anorexigenic effect. However, the molecular mechanisms involved in this
      phenomenon are poorly characterized. In this study, we investigate the capacity
      of TNF-alpha to activate signal transduction in the hypothalamus through elements
      of the pathways employed by the anorexigenic hormones insulin and leptin. High
      dose TNF-alpha promotes a reduction of 25% in 12h food intake, which is an
      inhibitory effect that is marginally inferior to that produced by insulin and
      leptin. In addition, high dose TNF-alpha increases body temperature and
      respiratory quotient, effects not reproduced by insulin or leptin. TNF-alpha,
      predominantly at the high dose, is also capable of activating canonical pro
      inflammatory signal transduction in the hypothalamus, inducing JNK, p38, and
      NFkappaB, which results in the transcription of early responsive genes and
      expression of proteins of the SOCS family. Also, TNF-alpha activates signal
      transduction through JAK-2 and STAT-3, but does not activate signal transduction
      through early and intermediary elements of the insulin/leptin signaling pathways
      such as IRS-2, Akt, ERK and FOXO1. When co-injected with insulin or leptin, TNF
      alpha, at both high and low doses, partially impairs signal transduction through
      IRS-2, Akt, ERK and FOXO1 but not through JAK-2 and STAT-3. This effect is
      accompanied by the partial inhibition of the anorexigenic effects of insulin and
      leptin, when the low, but not the high dose of TNF-alpha is employed. In
      conclusion, TNF-alpha, on a dose-dependent way, modulates insulin and leptin
      signaling and action in the hypothalamus.

PMID- 17459525
TI  - Neuronal regulation by which microglia enhance the production of neurotrophic
      factors for GABAergic, catecholaminergic, and cholinergic neurons.
AB  - A phenomenon-in which microglia are activated in axotomized rat facial nucleus
      suggests that a certain neuronal stimulus triggers the activation of microglia.
      However, how the microglial characteristics are regulated by this neuronal
      stimulus has not previously been determined. In this study, therefore, the
      regulation of microglial properties by neurons was characterized in vitro from a
      neurotrophic perspective. To evaluate the neurotrophic effects of microglia
      stimulated with neurons, the effects of conditioned medium (CM) of microglia
      stimulated with neuronal CM (NCM) were assessed in neuronal cultures. The amounts
      of tyrosine hydroxylase (TH) in neuronal culture exposed to CM of microglia
      stimulated with NCM was much more than those in neurons exposed to CM of control
      microglia, suggesting that neuronal stimulus enhances the production of
      neurotrophic factors for catecholaminergic neurons in microglia. Therefore, the
      neurotrophic effects of CM of microglia stimulated with NCM were analyzed in
      detail. The immunocytochemical and biochemical experiments revealed that the CM
      of microglia stimulated with NCM enhances the survival/maturation of GABAergic
      and catecholaminergic neurons. The levels of choline acetyltransferase specific
      to cholinergic neurons also significantly increased in response to stimulation
      with the same microglial CM. These results allowed us to investigate the
      production of neurotrophic factors in the CM of microglia stimulated with NCM.
      The results indicated that NCM induces nerve growth factor (NGF), and enhances
      neurotrophin-4/5 (NT-4/5), transforming growth factor beta1 (TGFbeta1), glial
      cell line-derived neurotrophic factor (GDNF), fibroblast growth factor 2 (FGF2),
      interleukin-3 (IL-3), and IL-10 in microglia. The promoted neurotrophic effects
      of CM of microglia stimulated with NCM were significantly abrogated by
      deprivation of neurotrophic factors by means of an immunoprecipitation method.
      Taken together, neuronal stimulus was found to activate microglia to produce more
      neurotrophic factors as above, thereby changing microglia into more neurotrophic
      cells.

PMID- 17459526
TI  - Inhibition of p38 mitogen-activated protein kinase-induced apoptosis in cultured
      mature oligodendrocytes using SB202190 and SB203580.
AB  - p38 Mitogen-activated protein kinase (p38 MAPK) is expressed in the
      oligodendrocyte lineage, and its activity has been implicated in the
      proliferation and transition of early progenitors into late progenitors. Although
      p38 MAPK expression has been found in the myelin sheath, however, its role in
      mature oligodendrocytes remains unknown. In the present study, in order to
      address the role of p38 MAPK in mature oligodendrocytes, selective inhibitors of
      p38 MAPK, SB202190, and SB203580 were added to primary cultures of mature
      oligodendrocytes. After 24h of exposure to the inhibitors, the appearance, and
      number of A2B5-positive progenitors were unchanged. However, the 2',3'-cyclic
      nucleotide-3'-phosphohydrolase-positive mature oligodendrocytes disappeared, and
      the numbers of living cells decreased in comparison to the control cells treated
      with SB202474, a negative analog of SB203580. Increases in the number of terminal
      deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive nuclei and
      in the activity of caspase-3/7 were detected 16 h after exposure to the
      inhibitors, thus causing the mature oligodendrocytes to die due to apoptosis.
      Similar results were obtained using a differentiated rat oligodendrocyte
      precursor cell (OPC) line, central glia-4 (CG-4). These findings indicate that
      p38 MAPK is vital for mature oligodendrocyte survival.

PMID- 17459527
TI  - N-truncated amyloid-beta oligomers induce learning impairment and neuronal
      apoptosis.
AB  - N-terminal-truncated forms of amyloid-beta (A beta) peptide have been recently
      suggested to play a pivotal role early in Alzheimer's disease (AD). Among them, A
      beta 3(pE)-42 peptide, starting with pyroglutamyl at residue Glu-3, is considered
      as the predominant A beta species in AD plaques and pre-amyloid lesions. Its
      abundance is reported to be directly proportional to the severity of the clinical
      phenotype. The present study investigates the effects of soluble oligomeric A
      beta 3(pE)-42 after intracerebroventricular injection on mice learning ability
      and the molecular mechanisms of its in vitro neurotoxicity. Mice injected with
      soluble A beta 3(pE)-42 or A beta(l-42) displayed impaired spatial working memory
      and delayed memory acquisition in Y-maze and Morris water maze tests, while those
      injected with soluble A beta(42-1) showed no effect. These cognitive alterations
      were associated with free radical overproduction in the hippocampus and olfactory
      bulbs, but not in the cerebral cortex or cerebellum. In vitro, A beta 3(pE)-42
      oligomers induced a redox-sensitive neuronal apoptosis involving caspase
      activation and an arachidonic acid-dependent pro-inflammatory pathway. These data
      suggest that A beta 3(pE)-42 could mediate the neurodegenerative process and
      subsequent cognitive alteration occurring in preclinical AD stages.

PMID- 17459529
TI  - Cytotoxic Mannich bases of 6-(3-aryl-2-propenoyl)-2(3H)-benzoxazolones.
AB  - A series of 12 new Mannich bases with chalcone core structure were synthesized as
      potential antineoplastic agents, via N-aminomethylation of two parent 6-(3-aryl-2
      propenoyl)-2(3H)-benzoxazolones. The newly synthesized compounds as well as the
      chalcone prototypes were evaluated for cytotoxicity in the human pre-B-cell
      leukemia cell line BV-173 using the MTT-dye reduction assay. The tested compounds
      exhibited concentration-dependent cytotoxic effects at low micromolar
      concentrations. Ten of the Mannich bases characterized by significant activity in
      BV-173 were further evaluated against the chronic myeloid leukemia cell line K
      562 and were found to suppress the growth of these cells at relatively higher
      concentrations as compared to the former tumor model. Selected Mannich bases
      induced programmed cell death in BV-173 at a concentration of 2.5muM as evidenced
      by the encountered DNA-laddering. Taken together our data suggest that the
      presented heterocyclic chalcone derived Mannich bases necessitate detailed
      pharmacological evaluation in order to define further the structure activity
      relationships, in a larger spectrum of tumor models and to elucidate the
      mechanisms implicated in the observed cytotoxic effects.

PMID- 17459530
TI  - Classification of estrogen receptor-beta ligands on the basis of their binding
      affinities using support vector machine and linear discriminant analysis.
AB  - Classification models of estrogen receptor-beta ligands were proposed using
      linear and nonlinear models. The data set was divided into active and inactive
      classes on the basis of their binding affinities. The two-class problem (active,
      inactive) was firstly explored by linear classifier approach, linear discriminant
      analysis (LDA). In order to get a more accurate prediction model, the nonlinear
      novel machine learning technique, support vectors machine (SVM), was subsequently
      used to investigate. The heuristic method (HM) was used to pre-select the whole
      descriptor sets. The model containing eight descriptors founded by SVM, showed
      better predictive ability than LDA. The accuracy in prediction for the training,
      test and overall data sets are 92.9%, 85.8% and 91.4% for SVM, 83.1%, 76.1% and
      81.9% for LDA, respectively. The results indicate that SVM can be used as a
      powerful modeling tool for QSAR studies.

PMID- 17459528
TI  - An MRI study of age-related white and gray matter volume changes in the rhesus
      monkey.
AB  - We applied the automated MRI segmentation technique Template Driven Segmentation
      (TDS) to dual-echo spin echo (DE SE) images of eight young (5-12 years), six
      middle-aged (16-19 years) and eight old (24-30 years) rhesus monkeys. We analyzed
      standardized mean volumes for 18 anatomically defined regions of interest (ROI's)
      and found an overall decrease from young to old age in the total forebrain
      (5.01%), forebrain parenchyma (5.24%), forebrain white matter (11.53%), forebrain
      gray matter (2.08%), caudate nucleus (11.79%) and globus pallidus (18.26%).
      Corresponding behavioral data for five of the young, five of the middle-aged and
      seven of the old subjects on the Delayed Non-matching to Sample (DNMS) task, the
      Delayed-recognition Span Task (DRST) and the Cognitive Impairment Index (CII)
      were also analyzed. We found that none of the cognitive measures were related to
      ROI volume changes in our sample size of monkeys.

PMID- 17459531
TI  - [Pericarditis in internal medicine].

PMID- 17459532
TI  - [Cardiac sarcoidosis].

PMID- 17459533
TI  - [Hypertension and the renin-angiotensin-aldosterone pathway].

PMID- 17459534
TI  - Heart failure: a disease for the Internist.

PMID- 17459535
TI  - [Workshop on subcutaneous immunoglobulins: why and how? Vivaglobin. SNFMI,
      December 7, 2006].

PMID- 17459537
TI  - Changes in nurse education: delivering the curriculum.
AB  - The aim of this study is to examine changes in pre-registration nursing education
      through the personal accounts of nurse teachers. This paper is based on 37 in
      depth interviews within a central London Healthcare Faculty. Each interview was
      subjected to a process of content analysis described by Miles and Huberman. The
      interviews took place between August 2003 and March 2004 and totalled 34.4 hours
      or 305,736 words. There were thirty female and seven male participants, who
      shared 1015 years of nursing experience, averaging at 27.4 years (min 7-max 42).
      These were supplemented by 552 years of teaching practice, the average being 15
      years (min 0.5-max 29). This paper--delivering the nursing curriculum--identifies
      that the nature of nursing has changed as it has both expanded and contracted.
      Participants identified three major changes; the nature of nursing, selection of
      future nurses and the current impact that large cohorts have on our traditional
      model of person-centred education. The practice placements remain central to
      nursing education and it is the nursing role that should define the curriculum
      and the values of higher education should be supportive of this identity.

PMID- 17459538
TI  - Matching purpose with practice: revolutionising nurse education with mita.
AB  - Multiple intelligences have only recently entered the teaching dialogue in nurse
      education and research. It is argued that despite the rhetoric of a student
      centred approach nurse education remains wedded to conventional teaching
      approaches that fail to engage with the individual and unwittingly silence the
      student's voice. This paper will examine the concept of multiple intelligences
      (MI) and outline Gardner's contention that the brain functions using eight
      intelligences which can be employed to improve learning at an individual level.
      It will then outline the use of MI using a five phase model, developed by Weber,
      known as a multiple intelligence teaching approach (MITA). It is contended that
      MITA has great potential in nurse education, particularly in terms of reinforcing
      learning beyond the educational domain and into the individual's professional
      development and clinical practice.

PMID- 17459539
TI  - Pandemic influenza planning: shouldn't swine and poultry workers be included?
AB  - Recent research has demonstrated that swine and poultry professionals, especially
      those who work in large confinement facilities, are at markedly increased risk of
      zoonotic influenza virus infections. In serving as a bridging population for
      influenza virus spread between animals and man, these workers may introduce
      zoonotic influenza virus into their homes and communities as well as expose
      domestic swine and poultry to human influenza viruses. Prolonged and intense
      occupational exposures of humans working in swine or poultry confinement
      buildings could facilitate the generation of novel influenza viruses, as well as
      accelerate human influenza epidemics. Because of their potential bridging role,
      we posit that such workers should be recognized as a priority target group for
      annual influenza vaccines and receive special training to reduce the risk of
      influenza transmission. They should also be considered for increased surveillance
      and priority receipt of pandemic vaccines and antivirals.

PMID- 17459540
TI  - Immunogenicity of candidate hepatitis E virus DNA vaccine expressing complete and
      truncated ORF2 in mice.
AB  - Hepatitis E virus (HEV) is a major cause of enterically transmitted acute
      hepatitis of adults in developing nations. Our present studies show that, the
      complete ORF2 gene (1-660 amino acids, a.a.) coding for capsid protein of HEV as
      candidate DNA vaccine induced significant specific humoral and cellular immune
      responses in mice. Gene gun based DNA administration led to higher seroconversion
      rates and HEV-specific antibody titers as against needle-injection method. The
      region (458-607a.a.) within ORF2 protein is reported to harbour the predominant
      neutralization epitope/s (NE) of HEV. The NE DNA also induced HEV-specific immune
      responses in mice. NE-based DNA-prime-protein boost approach was observed to be
      superior to NE DNA based approach. Co-administration of plasmid expressing mouse
      granulocyte macrophage colony stimulating factor (GM-CSF) induced immune response
      at similar level as that with ORF2/NE plasmid alone. IgG1 was the predominant
      isotype irrespective of the approach used. HEV-specific antibodies in
      seroconverted mice sera could bind/neutralize HEV in an in vitro ELISA-based
      assay. In conclusion, efficacy of ORF2 and NE based DNA/DNA-prime-protein-boost
      approaches are worth exploring in monkey model.

PMID- 17459541
TI  - Ecological impacts of umbrella effects of radiation on the individual members.
AB  - In order to study the interactions in a model aquatic microcosm, an individual
      based computer simulation model was developed. The microcosm consists of Euglena
      gracilis as an autotroph algae, Tetrahymena thermophila as a heterotroph protozoa
      and Escherichia coli as a saprotroph bacteria. There exists a strong interaction
      between Tetrahymena and E. coli as the first is the predator of the second.
      Ecological toxicity tests were conducted to test the population level impacts of
      the biological effects of radiation and toxicants on the lethality and mobility
      factors that influence directly or indirectly growth and reproduction.
      Radiological effects on lethality of E. coli individuals were translated to the
      reduction of the equilibrium population of Tetrahymena. A synergistic effect at
      the community level was also observed by the simulation of a combined exposure of
      radiation and a toxicant which reduced the feeding efficiency of Tetrahymena.

PMID- 17459542
TI  - Randomised-controlled trial of two antenatal education programmes.
AB  - OBJECTIVE: to determine whether a new antenatal education programme with
      increased parenting content could improve parenting outcomes for women compared
      with a regular antenatal education programme. DESIGN: a randomised-controlled
      trial. Data were collected through self-report surveys. SETTING: specialist
      referral maternity hospital in Sydney, Australia. PARTICIPANTS: 170 women
      birthing at the hospital. Ninety-one women attended the new programme and 79 the
      regular programme. INTERVENTION: a new antenatal education programme ('Having a
      Baby' programme) developed from needs assessment data collected from expectant
      and new parents. One important feature of the programme was the recognition that
      pregnancy, labour, birth and early parenting were a microcosm of the childbearing
      experience, rather than separate topics. MEASURES: the primary outcome measure
      was perceived maternal parenting self-efficacy. Worry about the baby, and
      perceived parenting knowledge, were secondary outcome measures. They were
      measured before the programme and after birth. Birth outcomes were also recorded.
      FINDINGS: the postnatal perceived maternal parenting self-efficacy scores of
      women who attended the 'Having a Baby' programme were significantly higher than
      those who attended the regular programme. Perceived parenting knowledge scores of
      women who attended the 'Having a Baby' programme were also significantly higher
      than those who attended the regular programme. Worry scores were lower but they
      did not reach statistical significant. Birth outcomes were similar. IMPLICATIONS
      FOR PRACTICE: the 'Having a Baby' programme improved maternal self-efficacy and
      parenting knowledge. Parenting programmes that continue in the early postnatal
      period may be beneficial.

PMID- 17459543
TI  - Biological degradation of triclocarban and triclosan in a soil under aerobic and
      anaerobic conditions and comparison with environmental fate modelling.
AB  - Triclocarban and triclosan are two antimicrobial agents widely used in many
      personal care products. Their biodegradation behaviour in soil was investigated
      by laboratory degradation experiments and environmental fate modelling.
      Quantitative structure-activity relationship (QSAR) analyses showed that
      triclocarban and triclosan had a tendency to partition into soil or sediment in
      the environment. Fate modelling suggests that either triclocarban or triclosan
      "does not degrade fast" with its primary biodegradation half-life of "weeks" and
      ultimate biodegradation half-life of "months". Laboratory experiments showed that
      triclocarban and triclosan were degraded in the aerobic soil with half-life of
      108 days and 18 days, respectively. No negative effect of these two antimicrobial
      agents on soil microbial activity was observed in the aerobic soil samples during
      the experiments. But these two compounds persisted in the anaerobic soil within
      70 days of the experimental period.

PMID- 17459544
TI  - Geographical Gerontology: the constitution of a discipline.
AB  - Health and healthcare have always been central considerations in geographical
      gerontology. This paper reviews progress in this part of the field over the past
      decade (1995-2006) and also looks to the future. It demonstrates how geographical
      gerontology is currently constituted of multiple fields of empirical interest
      studied by multiple academic disciplines. Specifically, the continuation and
      development of traditional perspectives on older population health--in terms of
      dynamics, distributions and movements--are traced, as well as emerging post
      modern perspectives and qualitative approaches that sensitively investigate the
      complex relationships between older people and the varied places within which
      they live and are cared for. Mirroring theoretical developments and diversity in
      the social sciences, the future research challenges that lie ahead will involve
      the articulation of varied and often hidden cultural practices and social
      processes, and hitherto taken-for-granted--as well as new--social and spatial
      relations, between older people, health and place. If however geographical
      gerontology is to meet these challenges most effectively, there has to be greater
      collaboration and communication within and between its constituent disciplines
      and diverse empirical areas. This will help it become recognized to a greater
      degree as a distinct discipline.

PMID- 17459545
TI  - Rethinking nurses' observations: psychiatric nursing skills and invisibility in
      an acute inpatient setting.
AB  - In sociological, managerial and clinical investigations of psychiatric nursing,
      the skills of observing patients are compared unfavourably with nurses' ability
      to listen, to interview and to engage with patients. This paper examines how
      nurses in an acute psychiatry unit used observation as a significant part of
      their everyday assessments of patients, through a working shift. We argue that
      the knowledge generated in observations is essential to the nurses' gaze in this
      setting. Based on an ethnographic study of the assessment practices of 11
      psychiatric nurses and the first author in an Australian hospital setting, we
      found that nurses' observations of patients were rich in situated assessment
      detail and a powerful strategy for producing civil conduct among patients. In
      particular, we noted how nurses deliberately obscured their practice of
      observation, in order not to provoke patients. While such discreet practice is
      productive for everyday clinical work, the invisibility of nursing observations
      undermines the status of acute inpatient psychiatric nurses. Devaluing of tacit
      practice may encourage experienced nurses to leave inpatient units, at a time
      when hospitals struggle to address nursing shortages worldwide. We recommend
      instead that the productive value of diverse and situated practices be
      investigated and articulated.

PMID- 17459546
TI  - "If you get AIDS... you have to endure it alone": understanding the social
      constructions of HIV/AIDS in China.
AB  - Recent AIDS research has documented the widespread discrimination toward people
      living with HIV/AIDS (PLWHA) in China. General ignorance and misconceptions about
      this disease have been identified as the two primary reasons for this prejudice.
      Yet, little attention has been paid to social constructions of HIV/AIDS in the
      Chinese context and to the processes by which such constructions are experienced,
      understood, reacted to, and, perhaps, reconstructed through social and
      interpersonal interactions. Based on a qualitative study of Chinese PLWHA's
      illness experiences, this paper explores how HIV/AIDS, as a social construct, is
      understood by these individuals in the context of their daily encounters. It is
      discovered that, despite their knowledge of HIV/AIDS, PLWHA's perceptions about
      and responses to this disease are greatly influenced by their experiences of
      interacting with others (e.g., their families, friends, and health workers). The
      conflicts between individuals' mastery of knowledge pertaining to, and their
      overreactions in practice toward, HIV-infected bodies suggest that AIDS education
      should not be limited to the dissemination of knowledge per se, but that the
      interpersonal or interactive dimensions of discrimination and efforts to combat
      it must also be taken into account.

PMID- 17459547
TI  - Characteristics and clinical correlates of restless legs syndrome in
      schizophrenia.
AB  - OBJECTIVE: The cause of restless legs syndrome (RLS) has not yet been
      ascertained, but one of the most promising theories involves dopaminergic
      deficiency. In accordance with this theory, we assumed that the prevalence of RLS
      would be higher among schizophrenics treated with antipsychotics than in the
      normal population. The purpose of this study was to establish the prevalence,
      characteristics, and clinical correlates of RLS in schizophrenic patients
      undergoing treatment with antipsychotics. METHODS: A total of 182 hospitalized
      schizophrenic patients and 108 age- and sex-matched normal controls were
      enrolled. The presence of RLS and its severity were assessed using the
      International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria and
      the IRLSSG rating scale, respectively. The Athens Insomnia Scale (AIS), Brief
      Psychiatric Rating Scale (BPRS), and Barnes Akathisia Rating Scale (BARS) were
      used to evaluate insomnia, global psychiatric symptoms, and akathisia,
      respectively, in schizophrenic patients. RESULTS: Of the 182 schizophrenic
      patients, 39 (21.4%) were found to have RLS and 87 (47.8%) met at least one of
      the RLS diagnostic criteria. The prevalence of RLS was significantly higher in
      the schizophrenia group than in the control group (p=0.009), as were the RLS
      scores (p<0.001). The BPRS (p=0.001) and the AIS (p<0.001) scores were higher in
      the RLS group than in the group with no RLS symptoms. CONCLUSION: We conclude
      that it is important to consider the diagnosis of RLS when schizophrenic patients
      complain of insomnia, and that RLS symptoms could be associated with more severe
      psychiatric symptoms and insomnia.

PMID- 17459548
TI  - Oxidative-antioxidative systems and their relation with serum S100 B levels in
      patients with schizophrenia: effects of short term antipsychotic treatment.
AB  - Oxidative stress may be a contributing factor in the etiopathophysiology of
      schizophrenia, which may be exacerbated by the treatment with antipsychotics with
      pro-oxidant properties. Increased levels of S100 B are associated with
      neurodegenerative disorders, including schizophrenia. The aim of the present
      study was to investigate the role of oxidative cell damage in the pathogenesis of
      schizophrenia. Forty patients who fully met the fourth Diagnostic and Statistical
      Manual of Mental Disorders criteria for schizophrenia and 35 healthy control
      subjects were included in the study. Serum S100 B level was determined to
      investigate brain damage. Plasma malondialdehyde (MDA) levels and susceptibility
      of red blood cell (RBC) to oxidation were determined to investigate the oxidative
      status and plasma vitamin E, vitamin C, serum total carotenoid levels and total
      antioxidant capacity and RBC superoxide dismutase (SOD) and whole blood
      glutathione peroxidase activities were measured to investigate the antioxidative
      defence before and after 6 weeks of antipsychotic treatment. Plasma MDA and serum
      S100 B levels and RBC-SOD activity were significantly higher in the schizophrenia
      group than those of the control group. Treatment did not modify any of the
      oxidative-antioxidative system parameters or serum S100 B levels. S100 B level
      was significantly higher in patients with negative symptoms than the patients
      with positive symptoms and the control subjects. S100 B levels were significantly
      reduced after 6 weeks of treatment in patients with negative symptoms. The
      results of the present study might support the oxidative cell injury hypothesis
      of the schizophrenia. Furthermore, the underlying mechanisms of the subgroups of
      schizophrenia might be different as suggested by the increased S100 B levels and
      its decrement after treatment in patients with negative symptoms.

PMID- 17459549
TI  - Treatment with risperidone for 4 weeks increased plasma 3-methoxy-4
      hydroxypnenylglycol (MHPG) levels, but did not alter plasma brain-derived
      neurotrophic factor (BDNF) levels in schizophrenic patients.
AB  - In the present study, we investigated the effects of risperidone treatment for 4
      weeks on plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and brain
      derived neurotrophic factor (BDNF) in 89 schizophrenic patients. We also compared
      the plasma levels of BDNF and MHPG between the schizophrenic group and 103 sex
      and age-matched normal controls. In addition, we investigated the effects of two
      SNPs of the noradrenaline transporter (NAT) gene on plasma levels of MHPG, BDNF,
      and clinical improvement. The mean dose of risperidone was 3.8+/-1.4 mg/day. We
      demonstrated that treatment with risperidone increased plasma MHPG levels, and
      this increase was associated with an improvement of the negative symptoms of
      schizophrenia. In contrast, plasma BDNF did not change after 4 weeks of
      risperidone treatment, and the two SNPs in NAT did not influence the response to
      risperidone treatment or plasma MHPG and BDNF levels. These results suggest that
      the enhancement of noradrenergic neurons by risperidone, which occurs
      independently of the two SNPs of NAT, plays a role in the clinical efficacy of
      the drug.

PMID- 17459550
TI  - Effects of paroxetine or milnacipran on serum brain-derived neurotrophic factor
      in depressed patients.
AB  - Brain-derived neurotrophic factor (BDNF) is an important member of the
      neurotrophin family of growth factors, abundant in the brain and periphery.
      Researchers have reported that serum BDNF levels in drug-free depressed patients
      are lower than those of healthy controls, and have proposed that these low levels
      might reflect a failure of neuronal plasticity in depression. In the present
      study, we investigated the effects of paroxetine, an SSRI, and milnacipran, an
      SNRI, on serum BDNF levels in depressed patients. Serum levels of BDNF were
      measured by ELISA before, 4 weeks, and 8 weeks after the start of treatment with
      antidepressants. Forty-two patients were randomly administered paroxetine (21
      cases) or milnacipran (21 cases). A negative correlation was found between serum
      BDNF levels and baseline Ham-D scores. The response and remission rates for each
      drug were not significantly different. Serum BDNF levels in responders were
      significantly increased 2.6- and 1.8-fold 8 weeks after treatment with paroxetine
      or milnacipran, respectively. These results suggest that both drugs improve the
      depressive state by increasing BDNF levels.

PMID- 17459551
TI  - Bipolar disorder: how far are we from a rigorous definition and effective
      management?
AB  - Bipolar disorder is a pathological disturbance of mood, characterized by waxing
      and waning manic, depressive and, sometimes distinctly mixed states. A diagnosis
      of bipolar disorder can only be made with certainty when the manic syndrome
      declares itself. Most individuals who are diagnosed with this disorder will
      experience both poles of the illness recurrently, but depressive episodes are the
      commonest cause of morbidity and, indeed, of death by suicide. Twin, adoption and
      epidemiological studies suggest a strongly genetic aetiology. It is a genetically
      and phenotypically complex disorder. Thus, the genes contributing are likely to
      be numerous and of small effect. Individuals with bipolar disorder also display
      deficits on a range of neuropsychological tasks in both the acute and euthymic
      phases of illness and correlations between number of affective episodes
      experienced and task performance are commonly reported. Current self-report and
      observer-rated scales are optimized for unipolar depression and hence limited in
      their ability to accurately assess bipolar depression. The development of a
      specific depression rating scale will improve the assessment of bipolar
      depression in both research and clinical settings. It will improve the
      development of better treatments and interventions. Guidelines support the use of
      antidepressants for bipolar depression. With regard to the adverse effects of
      antidepressants for bipolar depression, double-blind, placebo-controlled data
      suggest that antidepressant monotherapy or the addition of a tricyclic
      antidepressant may worsen the course of bipolar disorder. Importantly, adjunctive
      psychotherapies add significantly (both statistically and clinically) to the
      efficacy of pharmacological treatment regimens. The successful management of
      bipolar disorder clearly demands improved recognition of bipolar disorder and
      effective long-term treatment for bipolar depression as well as mania.

PMID- 17459552
TI  - The effects of inhalation anaesthetics on common clinical pathology parameters in
      laboratory rats.
AB  - Effects of common anaesthetics such as ether, methoxyflurane, isoflurane, carbon
      dioxide (at 100%, 80% or 60% admixed with O(2)) on toxicity and clinical
      pathology parameters in rats were investigated. Ether, methoxyflurane and 100%
      CO(2) induced toxicity in some animals. Erythrocyte, haemoglobin and haematocrit
      were reduced in females by 100% CO(2), methoxyflurane and isoflurane. Glucose was
      increased by 60% CO(2), 80% CO(2), ether, isoflurane and methoxyflurane in males.
      Chloride was reduced by isoflurane and all CO(2) concentrations in females. Serum
      proteins were reduced by isoflurane and methoxyflurane. Sodium, inorganic
      phosphate, calcium and magnesium were reduced by methoxyflurane and isoflurane,
      but increased by all CO(2) concentrations. Potassium was reduced by ether,
      methoxyflurane or isoflurane. Triiodothyronine and thyroxine were reduced by all
      anaesthetics. Prolactin was reduced by methoxyflurane, but raised by ether and
      isoflurane. Erythrocyte cholinesterase (E-ChE) activity is markedly reduced (20
      40%) after anaesthesia with all CO(2) concentrations in both sexes. E-ChE was
      unaffected by ether, methoxyflurane, or isoflurane. Serum and brain
      cholinesterase activities were not affected. E-ChE inhibition correlated with
      decreased blood pH, suggesting that this was caused by acidosis. This is of
      practical relevance in the risk assessment of cholinesterase inhibitors.
      CONCLUSIONS: Clinical pathology data were affected by all anaesthetics.
      CO(2)/O(2) (80%/20%) and isoflurane are the most suitable anaesthetics. If E-ChE
      activity is to be determined, isoflurane is the anaesthetic of choice.

PMID- 17459553
TI  - Effect of Lactarius piperatus fruiting body maturity stage on antioxidant
      activity measured by several biochemical assays.
AB  - The effects of fruiting body maturity on antioxidant activity and antioxidants
      production of the wild mushroom, Lactarius piperatus, were evaluated. Several
      biochemical assays were used to screen the antioxidant properties: reducing
      power, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity,
      inhibition of erythrocytes hemolysis mediated by peroxyl radicals and inhibition
      of lipid peroxidation using the beta-carotene linoleate model system. The amounts
      of phenols, flavonoids, ascorbic acid, beta-carotene and lycopene present in the
      immature, mature and degraded fruiting bodies were also determined. The highest
      antioxidant contents and the lowest EC(50) values for antioxidant activity were
      obtained in the mature stage with immature spores.

PMID- 17459554
TI  - DNA solution(R) in cigarette filters reduces polycyclic aromatic hydrocarbon
      (PAH) levels in mainstream tobacco smoke.
AB  - Tobacco consumption represents a major health hazard to humans and, despite anti
      smoking campaigns, the number of smokers remains high; thus the reduction of
      toxic compounds from tobacco smoke may reduce the health hazards of smoking. In
      the last 25 years cigarette manufacturers have introduced a variety of filter
      designs to reduce toxic and carcinogenic substances in tobacco smoke (normal
      filters, NF). However, large quantities of harmful constituents are inefficiently
      retained by commonly used cigarette filters. Following a patented method we
      modified commercial cigarette filters (modified filter, MF) by injecting a DNA
      solution into the filter tips; we then evaluated the reduced polycyclic aromatic
      hydrocarbon (PAH) levels in mainstream tobacco smoke of MF relative to NF. The
      PAH measured were: fluoranthene (FLUO), pyrene (PY), benzo(a)anthracene (B(a)A),
      chrysene (CRY), benzo(a)pyrene (B(a)P), benzo(b)fluoranthene (B(b)F),
      benzo(k)fluoranthene (B(k)F), benzo(g,h,i)perylene (BGP), dibenzo(a,h)anthracene
      (DBA). The levels of PAH in cigarette smoke after MF were significantly reduced
      (P<0.001) compared to NF, using a variety of cigarette brands in a smoking
      machine (44.5%+/-8.4 % and 41.8%+/-5% for total and carcinogenic PAH,
      respectively, means+/-SE). Using B(a)P(TEF) values the reduction in PAH
      concentrations were similar for all cigarette brands with the exception of Camel,
      where the reduction was lower considering B(a)P(TEF) values. Amongst carcinogenic
      PAH, B(a)A, B(b)F and B(k)F) were reduced by 50-58%, CRY, B(a)P and DBA by about
      40%. In conclusion MF filters treated with DNA have the potential of decreasing
      the exposure to PAH in cigarette smoke. Since, unlike some previously proposed
      biological filters MF do not retain additional nicotine, the main addictive
      compound of tobacco smoke, these filters may not induce increased smoking to
      compensate for the reduction in the nicotine delivery to smokers.

PMID- 17459555
TI  - Variability and uncertainty assessment of patulin exposure for preschool children
      in Flanders.
AB  - The objective of the present study was to evaluate the patulin exposure of
      children consuming organic, handcrafted or conventional apple juice through a
      probabilistic approach and to evaluate the effectiveness of several risk
      management options aiming to reduce the risk for children due to patulin
      exposure. However, a large part of the data on patulin contamination of apple
      juice fell under the limit of detection (LOD). Different methods were tested to
      deal with these so-called left censored data and a uniform distribution with
      uncertain bounds was selected to handle this censorship. Variability and
      uncertainty assessment of patulin exposure showed that 0.9% [90% confidence
      interval (CI): 0.3-1.8%] of the children consuming only organic apple juice
      exceed the tolerable daily intake (TDI). For consumers of conventional and
      handcrafted apple juice this was respectively 0.1% [90% CI: 0-0.3%] and 0% [90%
      CI: 0-0.2%]. Reduction of the patulin contamination in apple juice to
      concentrations below 25 microg/kg reduced the percentage of the children
      exceeding the TDI to 0% [90%CI: 0-0.2%] for organic apple juice. Reduction of the
      apple juice consumption was less effective than a reduction of the patulin
      concentration in apple juice and is only useful when the patulin concentration of
      apple juice is below 25 microg/kg.

PMID- 17459556
TI  - Iron chelation-afforded cardioprotection against chronic anthracycline
      cardiotoxicity: a study of salicylaldehyde isonicotinoyl hydrazone (SIH).
AB  - Pyridoxal-derived aroylhydrazone iron chelators have been previously shown as
      effective cardioprotectants against chronic anthracycline cardiotoxicity. In this
      study we focused on a novel salicylaldehyde analogue (salicylaldehyde
      isonicotinoyl hydrazone, SIH), which has been recently demonstrated to possess
      marked and dose-dependent protective effects against oxidative injury of
      cardiomyocytes. Therefore, in the present study the cardioprotective potential of
      SIH against daunorubicin (DAU) cardiotoxicity was assessed in vitro (isolated rat
      ventricular cardiomyocytes; DAU 10 microM, 48 h exposure) as well as in vivo
      (chronic DAU-induced cardiomyopathy in rabbits; DAU 3mg/kg, i.v. weekly, 10
      weeks). In vitro, SIH (3-100 microM) was able to partially, but significantly
      decrease the LDH leakage from cardiomyocytes. In vivo, SIH co-administration was
      capable to reduce (SIH dose of 0.5mg/kg, i.v.) or even to completely prevent
      (1.0mg/kg, i.v.) the DAU-induced mortality. Moreover, the latter dose of the
      chelator significantly improved the left ventricular function (LV
      dP/dt(max)=1185+/-80 kPa/s versus 783+/-53 kPa/s in the DAU group; P<0.05) and
      decreased the severity of the myocardial morphological changes as well as the
      plasma levels of cardiac troponin T. Unfortunately, further escalation of the SIH
      dose (to 2.5mg/kg) resulted in a nearly complete reversal of the protective
      effects as judged by the overall mortality, functional, morphological as well as
      biochemical examinations. Hence, this study points out that aroylhydrazone iron
      chelators can induce a significant cardioprotection against anthracycline
      cardiotoxicity; however, they share the curious dose-response relationship which
      is unrelated to the chemical structure or the route of the administration of the
      chelator.

PMID- 17459557
TI  - A clinical study in situ to assess the effect of a food approved polymer on the
      erosion potential of drinks.
AB  - OBJECTIVES: The consumption of acidic soft drinks continues to rise as do
      concerns regarding effects of frequent intake. The aim of the study was to
      determine the effect of acidic soft drinks containing food approved polymers, on
      dental enamel. METHODS: The study design was a single blind, randomised, five
      treatment crossover clinical trial involving 15 healthy dentate subjects.
      Subjects wore an upper removable acrylic appliance retaining two enamel specimens
      and consumed 250ml of beverage four times/day for 10 days. The following
      beverages were tested: (1) unmodified acidic soft drink, (2) experimental acidic
      soft drink with 0.02% polyphosphate, (3) experimental acidic soft drink with
      0.02% polyphosphate and 0.01% calcium, (4) experimental acidic soft drink with
      0.02% polyphosphate and 0.03% xanthan gum, and (5) mineral water. Tissue loss was
      measured at days 5 and 10 of each study leg using a profilometer. RESULTS: The
      order of erosion from most to least at day 10 was unmodified acidic soft
      drink>experimental acidic soft drink with polyphosphate>experimental acidic soft
      drink with polyphosphate+gum>experimental acidic soft drink with
      polyphosphate+calcium>mineral water. At day 10 the unmodified acidic soft drink
      was significantly (p=0.001) more erosive than all other drinks. CONCLUSIONS:
      Unmodified acidic soft drink with the addition of polyphosphate alone or combined
      with calcium or xanthan gum are all effective at reducing erosion of enamel
      compared with the unmodified soft acidic drink.

PMID- 17459558
TI  - Modulation of the efficiency of a siRNA directed against MDR1 expression in MCF7
      R cells when combined with a second siRNA.
AB  - Effective silencing of MDR1, one of the genes involved in the multidrug
      resistance phenotype, can be achieved by the use of an efficient siRNA
      transfected into the doxorubicin-selected MCF7-R human cell line, alone or
      combined with a moderately efficient siRNA. On the contrary, there is no MDR1
      silencing when it is co-transfected with a control siRNA that does not target the
      human genome. This results from the limited amount of RISC (RNA-Induced Silencing
      Complex) in human cells, leading to competition between siRNAs. In the case where
      the energy difference between the extremities of one of the siRNAs is largely
      superior to that of the other one, competition between the siRNAs appear to be
      favorable for the former. It is suggested that designing efficient siRNAs from
      thermodynamic characteristics is favored when siRNAs are incorporated into the
      RISC Loading Complex (RLC) rather than directly loaded into RISC.

PMID- 17459559
TI  - Effect of an Asp80Ala substitution on the binding of dUTP and dUMP to Trypanosoma
      cruzi dUTPase.
AB  - dUTPase (deoxyuridine 5'-triphosphate nucleotide hydrolase) is an enzyme
      responsible for maintaining low levels of intracellular dUTP and thus prevents
      uracil incorporation into DNA by DNA polymerases during replication and repair
      processes. The thermodynamics of binding for both dUTP and dUMP (deoxyuridine 5'
      monophosphate) to the D80A mutant form of Trypanosoma cruzi dUTPase have been
      investigated by fluorescence spectroscopy and high-sensitivity isothermal
      titration calorimetry. In the presence of magnesium, approximately a 30-fold
      decrease in the value of the k(cat) and a 15-fold increase in the K(m) for dUTP
      hydrolysis was calculated while a 5-fold decrease was observed in the affinity
      for dUMP. In the absence of magnesium, the affinity for dUTP binding was similar
      for both enzymes while that for dUMP was lowered 3-fold as a consequence of the
      mutation. Calorimetric titrations in several buffers with different ionization
      heats rendered similar proton exchanges during the binding of dUMP. Thus,
      apparently the side chain of Asp 80 does not seem to vary its protonation state
      during the binding process. The enthalpy change values for the D80A mutant hardly
      change with temperature and, in addition, were Mg(2+) independent. We conclude
      that the D80A mutation induces only a slight conformational change in the active
      site yet results in a significant alteration of nucleotide binding and modifies
      the ability of the enzyme to discriminate between dUTP and dUMP when magnesium is
      present.

PMID- 17459560
TI  - Lightning, sudden cardiac death, simulation and an automated external
      defibrillator: the perfect storm.
AB  - This is a report of an 11-year-old boy who had sudden cardiac death after a
      lightning strike while playing lacrosse at summer camp. The camp staff had
      performed weekly drills to prepare for various medical emergencies and quickly
      activated their "Emergency Activation System". The child received immediate
      cardiopulmonary resuscitation (CPR) and was defibrillated with an automated
      defibrillator (AED) within 3 min of becoming pulseless and was ultimately
      resuscitated after being defibrillated three times. A community ambulance with a
      defibrillator on board did not arrive until several minutes after the on-site
      team had achieved return of spontaneous circulation. In this report, we describe
      the clinical course of this patient; briefly review lightning injuries, other
      causes of sudden cardiac death in children and use of AEDs. Finally, we review
      how simulation has been used in this case and others as a mechanism to ensure
      preparedness for medical emergencies. This child is alive and well today because
      of these well-trained camp counselors. Their system of using simulation to
      maintain emergency readiness serves as an example for lay and professional
      medical providers alike.

PMID- 17459561
TI  - The voice advisory manikin (VAM): an innovative approach to pediatric lay
      provider basic life support skill education.
AB  - AIM: To determine the efficacy of immediate, standardized, corrective audio
      feedback training as supplied by the voice advisory manikin (VAM) compared to
      high quality standardized instructor feedback training for the initial
      acquisition of 1-rescuer lay provider pediatric BLS skills. MATERIALS AND
      METHODS: Lay care providers of hospitalized children 8-18 years were randomized
      to VAM (n=23) or standardized human instruction (SHI, n=27) training in one
      rescuer pediatric BLS. After an identical video/instructor introduction to CPR
      and 20 min of training in their respective group, quantitative CPR psychomotor
      skill data was recorded during 3-min CPR testing epochs. All manikins used in
      training and testing sessions were identical in outside appearance and feel of
      doing CPR. The primary outcome measure was CPR psychomotor skill success defined
      prospectively as 70% correct chest compressions (CC) and ventilations (V).
      Subjects not attaining these success goals retrained for 5 min in their
      respective training group and were retested. Data analysis using student t-test
      and chi2-tests as appropriate. RESULTS: VAM trainees delivered more total CC/min
      (58.7+/-7.9 versus 47.6+/-10.5, p<0.001), correct CC/min (47.9+/-15.7 versus
      31.2+/-16.0, p<0.001), total V/min (7.8+/-1.2 versus 6.4+/-1.4, p<0.001), and
      correct V/min (5.4+/-1.9 versus 3.1+/-1.6, p<0.001). Overall error rates per
      individual were lower in VAM trainees for chest compressions (18.1+/-23.2% versus
      34.9+/-28.8%, p<0.03) and ventilations (32.0+/-19.7% versus 50.7+/-24.1%,
      p<0.005). More VAM (12/23, 52%) than SHI (1/26, 4%) trainees passed the initial
      skill tests (p<or=0.0001). After remediation and retesting, the difference in
      rate of attaining success goals remained significant: VAM 15/23, 65% versus SHI
      7/26, 27% (p=0.008). CONCLUSION: Immediate, standardized, corrective audio
      feedback training as supplied by the voice advisory manikin (VAM) can improve
      initial pediatric basic life support skill acquisition for lay providers even
      when compared to one-on-one, standardized instructor-led training.

PMID- 17459562
TI  - Enzyme linked immunosorbent assay (ELISA) as screening method for anti-paternal
      allo-antibodies in patients with recurrent pregnancy loss (RPL).
AB  - OBJECTIVES: Non-HLA-specific anti-paternal antibodies (APA) have been associated
      with immune responses against HLA-negative trophoblast. As screening for APA by
      using the flow cytometric cross match (FCXM) is complicated, we evaluated the One
      Lambda Antigen Tray Test (OLATT) an easy screening method for antibodies in organ
      transplant recipients. STUDY DESIGN: We randomly selected 92 patients of our
      recurrent pregnancy loss (RPL)-clinic merely on the basis of having had at least
      two consecutive miscarriages at <20 weeks representing positive and negative FCXM
      results. Stored sera were thawed and tested by OLATT. Concordance (Kappa
      statistic) and conformance (Chi-square test to McNemar) of FCXM and OLATT results
      were analysed. RESULTS: Of 48 FCXM-positive patients, 38 (79.2%) were positive
      and 10 (20.8%) negative by OLATT. Out of 44 FCXM negative patients, 37 (84.1%)
      were negative and 7 (15.9%) positive by OLATT. This resulted in a positive
      prediction value of 84.4%, a negative prediction value of 78.7% and a highly
      significant concordance (kappa=0.631 (p<0.0001; 81.5% versus 50%)) and
      conformance (p=0.23) between FCXM and OLATT in RPL patients. CONCLUSION: Using
      the OLATT could substitute the FCXM in screening RPL patients for APA and this
      might help to more closely study the role of APA in human gestation.

PMID- 17459563
TI  - Mesh-related infections after pelvic organ prolapse repair surgery.
AB  - The use of vaginal meshes has been an advance in the surgical management of women
      with pelvic organ prolapse. We reviewed the literature to synthesize the evidence
      regarding the infectious complications related to this new type of foreign body.
      We searched PubMed, current contents, and references of initially identified
      relevant articles and extracted data regarding the incidence, clinical
      manifestation, and management of vaginal mesh-related infections. The incidence
      of mesh-related infections and erosion ranged from 0 to 8%, and 0 to 33%,
      respectively, in the published studies. Various factors influence the development
      of vaginal mesh-related infectious complications such as the kind of biomedical
      material (e.g. filament structure, pore size) of the mesh, the type of procedure,
      the preventive measures taken, and the age and underlying comorbidity of the
      treated women. Non-specific pelvic pain, persistent vaginal discharge or
      bleeding, dyspareunia, and urinary or faecal incontinence are the most common
      manifestation of vaginal mesh-related infection. Clinical examination may reveal
      induration of the vaginal incision, vaginal granulation tissue, draining sinus
      tracts, and prosthesis erosion or rejection. Various pathogens have been
      implicated, including Gram-positive and Gram-negative aerobic and anaerobic
      bacteria. The management of mesh-related infections in women who underwent pelvic
      organ reconstruction is combined surgical and medical treatment. Although the use
      of vaginal meshes has become a new effective method of pelvic organ prolapse
      surgery clinicians should be aware of the various post-operative complications,
      including mesh-related infections.

PMID- 17459564
TI  - Re-evaluation of the indication for and limitation of laparoscopic salpingotomy
      for tubal pregnancy.
AB  - OBJECTIVE: We investigated the outcome of laparoscopic salpingotomy for tubal
      pregnancy by follow-up hysterosalpingography (HSG) or second-look laparoscopy
      (SLL) and reexamined the indication for and limitation of this conservative
      surgery. STUDY DESIGN: From April 1991 to December 2003, we treated 181 cases of
      tubal pregnancy using laparoscopic salpingotomy. The tubal patency was assessed
      by either HSG or SLL performed at 3 months post-surgery. The patients with a
      successful initial operation and confirmed ipsilateral patent tubes at follow-up
      were classified as truly successful cases (group I). Even after successful
      operation, if the treated tubes were found to be occluded, they were considered
      as unsuccessful cases. Therefore, those cases that were unsuccessful at initial
      surgery as well as at follow-up were categorized as group II. RESULTS: One
      hundred and thirty-four cases (74%) were successfully treated by salpingotomy at
      initial laparoscopy and 85 of them (63.4%) were found to be truly successful at
      follow-up (group I). The remaining 47 cases (26.0%) were unsuccessful at initial
      surgery and 18 (13.4%) cases at follow-up (group II). Thirty-one other patients
      refused to accept a tubal patency test or were not examined for personal reasons
      or were lost to follow-up. No difference in surgical outcome was observed between
      these two groups of patients with regard to gestational age, intra-operative
      hemorrhage, size or anatomic location of the pregnancy mass, and pre-operative
      adhesions of the fallopian tube. However, pre-operative serum levels of hCG were
      significantly higher in group II than in group I. In addition, the unsuccessful
      cases were more frequently associated with positive fetal heart beat (FHB), tubal
      rupture, and pre-operative serum levels of hCG of more than 10,000 IU/l (p<0.05,
      chi2 test). The log-rank test indicated a higher pregnancy success rate in group
      I (p<0.05) than in group II in those who desired future pregnancy. CONCLUSION:
      Laparoscopic salpingotomy may be practised as conservative surgery for proximal
      ectopic pregnancy, and gestational mass size is not as important and is not a
      relative contraindication for conservative laparoscopic surgery, as previously
      reported. Low pre-operative HCG levels, absence of FHB, absence of tubal rupture
      initially or minimal rupture may be considered suitable parameters for successful
      surgery and for achieving future pregnancy.

PMID- 17459566
TI  - Study of the biomechanical properties of synthetic mesh implanted in vivo.
AB  - OBJECTIVE: The objective was to assess in an animal model the mechanical
      properties of five prostheses used for pelvic floor repair. STUDY DESIGN: Two
      months after pre-peritoneal implantation of the five types of prosthesis:
      Prolene, Prolene Soft, Mersuture, Vicryl and Vypro, we sacrificed the animals to
      measure retraction of the prosthesis, maximal resistance to traction, and maximal
      elongation. RESULTS: Non-absorbable prostheses retracted least. Forces at rupture
      were disparate with a significant difference in favor of Prolene (p<0.001).
      Resistance was variably affected by cicatrization. There were no significant
      differences in elongation. CONCLUSIONS: This study is an introductory
      exploration. Monofilament and macroporous propylene prostheses seem, after
      implantation, to have the best mechanical performance and best tissue
      integration. This underlines the need for experimental prostheses, which are
      increasingly used, but still lack the extensive evaluation needed by the surgeon.
      Knitted polypropylene seems to be one of the best materials at present, but is
      probably not sufficient.

PMID- 17459567
TI  - C-reactive protein serum levels are closely associated with lymph node status,
      but not with prognosis in patients with vulvar cancer.
AB  - OBJECTIVE: To evaluate whether C-reactive protein (CRP) serum levels can be used
      as prognostic parameter in patients with vulvar cancer. STUDY DESIGN: CRP serum
      levels were measured at the time of first diagnosis of squamous cell vulvar
      cancer. Sixty-seven patients were enrolled; results were correlated to clinical
      data. RESULTS: Mean CRP serum levels in patients with vulvar cancer were 0.8
      (0.80)mg/dL. CRP serum levels were significantly associated with lymph node
      involvement (p=0.003), but not with tumor stage (p=0.03), histological grade
      (p=0.86) and patients' age (p=0.64). Univariate analysis showed lymph node
      involvement, tumor stage and histological grade, but not CRP serum levels and
      patients' age to be associated with overall survival. A multivariable analysis
      determined only lymph node involvement as independent prognostic parameter for
      disease-free interval and overall survival. CONCLUSION: CRP serum levels are
      closely associated with lymph node status but cannot be used as prognostic
      parameter in patients with vulvar cancer.

PMID- 17459568
TI  - Operative vaginal delivery and the use of episiotomy--a survey of practice in the
      United Kingdom and Ireland.
AB  - OBJECTIVE: To establish the views and current practice of obstetricians with
      regard to operative vaginal delivery and the use of episiotomy. STUDY DESIGN: A
      national survey of consultant obstetricians and specialist registrars practising
      in the United Kingdom and Ireland registered with the Royal College of
      Obstetricians and Gynaecologists (RCOG), London. A postal questionnaire was sent
      to all obstetricians with two subsequent reminders to non-responders. The choice
      of procedure for specific circumstances, instrument preference, use of episiotomy
      and views on the relationship between episiotomy use and anal sphincter tears at
      operative vaginal delivery were explored. RESULTS: The response rate was 80.4%.
      Instrument preference varied according to the fetal position and station and the
      grade of operator. Vacuum and forceps were both used for mid-cavity non
      rotational deliveries (64% and 56% reported frequent use respectively).
      Rotational vacuum was preferred for a mid-cavity mal-position (69%) followed by
      equal numbers using rotational forceps or manual rotation and forceps (34% and
      36%, respectively). Inexperienced operators were more likely to proceed directly
      to caesarean section (35%). A restrictive approach to use of episiotomy was
      preferred for vacuum delivery (72%) and a routine approach for forceps (73%).
      Obstetricians varied greatly in their perception of the relationship between
      episiotomy use and anal sphincter tears at operative vaginal delivery.
      CONCLUSION: There is wide variation in the use of episiotomy at operative vaginal
      delivery with uncertainty about its role in preventing anal sphincter tears. A
      randomised controlled trial would address this important aspect of obstetric
      care.

PMID- 17459569
TI  - Feasibility of water purification technology in rural areas of developing
      countries.
AB  - Water scarcity is threatening social and economic growth in rural areas of
      developing countries. There are potential markets for water purification
      technologies in these regions. The main focus of this article is to evaluate the
      social, economic and political feasibilities of providing water purification
      technologies to rural areas of developing countries. The findings of this
      research can serve as the basis for private investors interested in entering this
      market. Four representative regions were selected for the study. Economic,
      demographic, and environmental variables of each region were collected and
      analyzed along with domestic markets and political information. Rural areas of
      the developing world are populated with poor people unable to fulfill the basic
      needs for clean water and sanitation. These people represent an important group
      of potential users. Due to economic, social, and political risks in these areas,
      it is difficult to build a strong case for any business or organization focusing
      on immediate returns on capital investment. A plausible business strategy would
      be to approach the water purification market as a corporate responsibility and
      social investing in the short term. This would allow an organization to be well
      positioned once the economic ability of individuals, governments, and donor
      agencies are better aligned.

PMID- 17459570
TI  - Network design for water quality monitoring of surface freshwaters: a review.
AB  - To date, many water quality monitoring networks for surface freshwaters have been
      rather haphazardly designed without a consistent or logical design strategy.
      Moreover, design practices in recent years indicate a need for cost-effective and
      logistically adaptable network design approaches. There are many variables that
      need to be included in a comprehensive yet practical monitoring network: a
      holistic appraisal of the monitoring objectives, representative sampling
      locations, suitable sampling frequencies, water quality variable selection, and
      budgetary and logistical constraints are examples. In order to investigate the
      factors which affect the development of an effective water quality monitoring
      network design methodology, a review of past and current approaches is presented.

PMID- 17459571
TI  - Editorial comment on: impact of stone size, location, composition, impaction, and
      hydronephrosis on the efficacy of holmium:YAG-laser ureterolithotripsy.

PMID- 17459572
TI  - Editorial comment on: Impact of stone size, location, composition, impaction, and
      hydronephrosis on the efficacy of holmium:YAG-laser ureterolithotripsy.

PMID- 17459573
TI  - Impact of stone size, location, composition, impaction, and hydronephrosis on the
      efficacy of holmium:YAG-laser ureterolithotripsy.
AB  - OBJECTIVES: The impact and outcome of holmium:YAG-laser (Ho:YAG)
      ureterolithotripsy in treating proximal and distal ureteral stones was
      investigated. METHODS: A total of 543 patients harbouring proximal (n=194) or
      distal (n=349) ureteral stones underwent semirigid Ho:YAG ureterolithotripsy. The
      degree of hydronephrosis; stone size, location, impaction, and composition; and
      complication and stone-free rates were recorded. RESULTS: Mean stone size for
      proximal and distal stones was 7.1+/-3.6 mm and 6.2+/-2.5 mm, respectively. The
      stone-free rate on the first postoperative day was 79.4% for proximal and 96.8%
      for distal stones (p<0.0001). For proximal stones <10mm and > or =10mm,
      respectively, the stone-free rate was 80.5% and 74.3% (p=0.4) and for distal
      stones 97.3% and 94.3% (p=0.2). Stone-free rates for radio-opaque versus
      radiolucent stones in proximal stones were 79.6% versus 77.9% (p=0.8) and 97.6%
      versus 96.2% in distal stones (p=0.5). Impaction correlated significantly with
      stone-free rates (p<0.0001). Stone-free rates for nonimpacted versus impacted
      proximal stones were 85.8% versus 67.2% (p=0.003) and for distal stones 99.2%
      versus 91.4% (p<0.003), respectively. The presence or degree of hydronephrosis
      did not correlate with treatment success (p=0.4, p=0.8). The presence of
      intraoperative complications correlated significantly with proximal compared to
      distal ureteral stone location (p=0.004). Auxiliary measures in proximal versus
      distal stones were performed in 20.6% versus 2.9% (p<0.0001). CONCLUSIONS: In
      this series, stone-free rates in Ho:YAG ureterolithotripsy were significantly
      higher in distal and nonimpacted stones but were independent of stone size and
      composition and the degree of hydronephrosis. Ureterolithotripsy in proximal
      stones was associated with higher intraoperative complication and retreatment
      rates compared to distal stones.

PMID- 17459574
TI  - UDN glycoprotein regulates activities of manganese-superoxide dismutase,
      activator protein-1, and nuclear factor-kappaB stimulated by reactive oxygen
      radicals in lipopolysaccharide-stimulated HCT-116 cells.
AB  - This study was carried out to investigate the anti-inflammatory effects of
      glycoprotein (UDN glycoprotein, 116-kDa) isolated from Ulmus davidiana Nakai,
      which has been used to heal inflammatory diseases in Korean herbal medicine. We
      found that UDN glycoprotein has strong scavenging effect on the production of
      intracellular superoxide anion (O(2)(-)), hydrogen peroxides (H(2)O(2)), and
      nitric oxide (NO) without any cytotoxicity, and that the glycoprotein also
      selectively normalizes the aberrant activation of manganese-superoxide dismutases
      (Mn-SOD) activity in lipopolysaccaride (LPS)-treated cancerous human colon
      epithelial cells (HCT-116 cells). The results obtained from electrophoretic
      mobility shift assay (EMSA) and Western blot analysis showed that UDN
      glycoprotein blocks the DNA binding activities of nuclear factor-kappaB (NF
      kappaB) and activator protein-1 (AP-1), and attenuates the activities of NF
      kappaB subunits (p50 and p65), and AP-1 subunits (c-Jun and c-Fos), respectively.
      To further verify the anti-inflammatory effect of UDN glycoprotein, we
      investigated the activity of inducible nitric oxide synthase (iNOS),
      cyclooxygenase-2 (COX-2), and matrix metalloproteinases-9 (MMP-9) in LPS-treated
      HCT-116 cells, using Western blot analysis and gelatin zymographic assay. Results
      in this study indicated that 200mug/ml of UDN glycoprotein has inhibitory effects
      on the activations of iNOS, COX-2, and MMP-9. Therefore, UDN glycoprotein, a
      natural antioxidant, is a potential modulator of inflammatory signal pathways in
      LPS-treated HCT-116 cells.

PMID- 17459575
TI  - Inorganic selenium speciation in groundwaters by solid phase extraction on Dowex
      1X2.
AB  - A Dowex 1X2 resin separation technique followed by analysis with atomic
      absorption spectroscopy was evaluated for the study of inorganic selenium
      speciation in groundwaters. After Se(IV) and Se(VI) were retained on the resin
      column, Se(IV) and Se(VI) were eluted out by 0.1 and 1M nitric acid solutions.
      The method detection limit was 5.6 ng/L for both Se(IV) and Se(VI). Analysis of
      synthetic solutions consistently yielded more than 90% recovery of these two
      selenium forms with negligible cross-contamination. The results of spiked well
      waters show that this method can be applied at ultra-trace level of Se in
      groundwater and the interference of chloride ion can be neglected. Water samples
      collected from the monitoring wells in the Science-based Industrial Park, Hsin
      Chu, Taiwan, were analyzed. Average dissolved selenium concentrations were 32.1+/
      17.6 ng/L. The proportion of Se(VI) to the total dissolved selenium ranged from
      47.6 to 61.2% and an average of 53.8% in water samples analyzed.

PMID- 17459576
TI  - Discoloration of a red cationic dye by supported TiO(2) photocatalysis.
AB  - The degradation under UV, visible and sunlight irradiation of C.I. Basic Red 46
      (BR 46) dye used for acrylic fibers dyeing has been studied in a lab-scale
      continuous system with two different immobilized TiO(2) systems. Catalyst I was
      based on TiO(2) particles deposited on cellulose fibers; Catalyst II combined
      TiO(2) particles deposited on a layer of cellulose fibers (as in Catalyst I) with
      a layer of carbon fibers and finally a layer of cellulose fibers. The treatment
      of aqueous dye solutions and industrial wastewater contaminated with the same dye
      has been evaluated in terms of color removal and chemical oxygen demand (COD)
      decrease. With UV light, aqueous solutions containing dye were decolorized
      slightly more rapidly with Catalyst II than with Catalyst I. Sunlight was also
      very effective and experiments involving sunlight irradiation showed Catalyst II
      to be the more efficient, giving more than 90% discoloration after 20 min of
      treatment. Comparing the discoloration yield by adsorption or under visible light
      for both catalysts, it was observed that the difference between them is below 5%.
      The adsorption kinetics was found to follow a second-order rate law for Catalyst
      I and a first-order rate law for Catalyst II. The kinetics of photocatalytic
      degradation under UV or sunlight were found to follow a first-order rate law for
      both catalytic systems. Under sunlight the COD removal yield for textile
      wastewater reaches 33% with Catalyst I against 93% with Catalyst II.

PMID- 17459577
TI  - The use of the Novosol process for the treatment of polluted marine sediment.
AB  - The work presented in this article concerns polluted marine sediments. The
      article is divided into three parts. The first part discusses existing industrial
      procedures of treatment. The second part introduces the Novosol((R)) process,
      which was used for the treatment of polluted marine sediments. This process is
      based on the stabilization of heavy metals in the solid matrix by phosphatation
      and the destruction of organic matter by calcination. Finally, after a comparison
      had been made between environmental results obtained on both polluted marine
      sediments and inert ones, treated sediments were introduced in the production of
      clay bricks. The results obtained show that the Novosol process leads to the
      immobilization of most heavy metals and can be considered as an efficient tool
      for the stabilisation of polluted marine sediment. Thus, the results of physical
      and mechanical tests as compressive strength and water absorption indicate that
      performances obtained were comparable to standard brick values. These results
      confirm that, once treated, polluted sediments can be recycled.

PMID- 17459578
TI  - Catalytic thermal treatment of desizing wastewaters.
AB  - In the present study, catalytic thermal treatment (thermolysis) was investigated
      for the reduction of COD and color of the desizing wastewater under moderate
      temperature and atmospheric pressure conditions using various catalysts. The
      experimental runs were performed in a glass reactor equipped with a vertical
      condenser. The homogeneous copper sulfate catalyst was found to be the most
      active in comparison to other catalysts under similar operating conditions. A
      removal of about 71.6% chemical oxygen demand (COD) and 87.2% color of desizing
      wastewater was obtained with a catalyst concentration of 4 kg/m(3) at pH 4. The
      initial pH value of the wastewater showed a pronounced effect on the
      precipitation process. During the thermolysis, copper gets leached to the aqueous
      phase, the residue obtained after the treatment is rich in copper and it can be
      blended with organic manure for use in agricultural fields. The thermogravimetric
      analysis showed that the thermal oxidation of the solid residue obtained after
      thermolysis gets oxidized at a higher temperature range than that of the residue
      obtained from the desizing wastewater. The results lead to the conclusion that
      thermochemical precipitation is a very fast (instantaneous) process and would
      need a very small reactor vessel in comparison to other processes.

PMID- 17459579
TI  - Long and short-term performance of a stabilized/solidified electric arc furnace
      dust.
AB  - The application of class F fly ash, cement and lime to the
      Stabilization/Solidification (S/S) of electric arc furnace dust containing
      hazardous metals such as Zn, Pb, Cd, and Cr is described. The aim of the study
      was to determine the influence of the setting conditions during the S/S treatment
      and to know the behaviour of an aged solidified and stabilized waste. In order to
      determine the efficiency attained by the S/S process, USEPA TCLP, and other
      leaching tests have been accomplished. In addition, the compressive strength of
      the solidified waste at different times has been determined. In order to study
      the influence of the environmental conditions in which setting occurs,
      experiments were carried out with samples of the same composition, under
      different setting conditions: laboratory environment, stove at a temperature of
      40-60 degrees C and setting in a hermetically sealed plastic bag at room
      temperature. All the samples were subjected to the TCLP test at 28 days, and the
      metal content of the resulting leachates was analysed. The results show that in
      some cases the setting conditions of the mixtures have a noticeable influence on
      the characteristics of the leachate. The evolution with time of some S/S solids,
      one month after their manufacture and more than 9 years after that has also been
      evaluated, by means of their leaching behaviour. The results obtained in this
      work have shown, in all the laboratory cured samples that the leachate pH
      decrease in the course of time, and consequently the leaching behaviour is in
      general worse. This could be due to the carbonation of the S/S solid and the
      subsequent loss of alkalinity.

PMID- 17459580
TI  - Characteristics of phenol biodegradation in saline solutions by monocultures of
      Pseudomonas aeruginosa and Pseudomonas pseudomallei.
AB  - Phenol is a highly toxic and carcinogenic compound and its biodegradation is very
      important to meet the environmental regulations. Two bacterial strains capable of
      utilizing phenol as a sole source of carbon were isolated from the wastewater of
      a pharmaceutical industry. On the basis of morphological and biochemical
      characteristics these strains were identified as Pseudomonas aeruginosa and
      Pseudomonas pseudomallei. Both of these strains were very efficient for phenol
      degradation. P. pseudomallei degraded phenol at a maximum concentration of 1500
      mg L(-1) within seven days with a specific growth rate of 0.013 h(-1) and phenol
      degradation rate of 13.85 mg L(-1)h(-1). Maximum initial concentration of phenol
      utilized by P. aeruginosa was 2600 mg L(-1) with 0.016 h(-1) specific growth rate
      and 26.16 mg L(-1)h(-1) phenol degradation rate. Moreover, the effect of various
      salts i.e., NaCl, KCl, Na(2)SO(4) and K(2)SO(4) on the growth of these strains
      and phenol degradation rate (at 1000 mg L(-1)) was studied. In the presence of
      these salts, P. aeruginosa showed up to 1.53 and 1.34 times faster phenol
      degradation rate and specific growth rate, respectively as compared to P.
      pseudomallei. In addition, P. aeruginosa exhibited higher chemical oxygen demand
      (COD) and biochemical oxygen demand (BOD) reduction rates as compared to the
      strain P. pseudomallei.

PMID- 17459581
TI  - Development of bioreactor system for treatment of dioxin-contaminated soil using
      Pseudallescheria boydii.
AB  - We developed a conceptual feasible design of bioreactor system for treatment of
      dioxin-contaminated soils that uses the dioxin-degrading fungus Pseudallescheria
      boydii (P. boydii) we had isolated. The dioxin-degradation conditions in
      bioreactor treatment was established by clarifying the inhibiting factors for the
      growth of P. boydii using both real contaminated and laboratory prepared soils
      mixed with fly ash. In addition, ethanol extraction process as post-treatment
      methods for the remaining dioxins, and the sterilization conditions of P. boydii,
      i.e., a weakly pathogenic fungus, in the residue was investigated. The better
      growth conditions of P. boydii were found to be chloride ion concentration of
      less than 10 g/L and a pH of less than 9. Under these conditions, 7310 pg-TEQ/g
      of the soil was treated to 2860 pg-TEQ/g by the bioreactor process, and the
      dioxin concentration was further decreased to 580 pg-TEQ/g by ethanol extraction,
      resulting to total removal ratio of 92%. Furthermore, development of an effective
      sterilization method for living P. boydii in the residue increased the
      applicability of our bioreactor system for practical use in dioxin-contaminated
      sites.

PMID- 17459582
TI  - Batch sorption dynamics and equilibrium for the removal of cadmium ions from
      aqueous phase using wheat bran.
AB  - Studies on a batch sorption process using wheat bran as a low cost sorbent was
      investigated to remove cadmium ions from aqueous solution. The influence of
      operational conditions such as contact time, cadmium initial concentration,
      sorbent mass, temperature, solution initial pH, agitation speed and ionic
      strength on the sorption kinetics of cadmium was studied. Pseudo-second-order
      model was evaluated using the six linear forms as well as the non-linear curve
      fitting analysis method. Modeling of kinetic results shows that sorption process
      is best described by the pseudo-second-order model using the non-linear method.
      The sorption of cadmium was found to be dependent on initial concentration,
      sorbent mass, solution pH, agitation speed, temperature, ionic strength and
      contact time. The value of activation energy (12.38 kJ mol(-1)) indicates that
      sorption has a low potential barrier corresponding to a physical process.
      Sorption equilibrium isotherms at different temperatures was determined and
      correlated with common isotherm equations such as Langmuir and Freundlich models.
      It was found that the Langmuir model appears to well fit the isotherm data but a
      worse correlation was obtained by the Freundlich model. The five Langmuir linear
      equations as well as the non-linear curve fitting analysis method were discussed.
      Results show that the non-linear method may be a better way to obtain the
      Langmuir parameters. Thermodynamic parameters such as DeltaH degrees, DeltaS
      degrees and DeltaG degrees were calculated. These parameters indicate that the
      sorption of cadmium by wheat bran is a spontaneous process and physical in nature
      involving weak forces of attraction and is also endothermic.

PMID- 17459583
TI  - Use of adsorption process to remove organic mercury thimerosal from industrial
      process wastewater.
AB  - Carbon adsorption process is tested for removal of high concentration of organic
      mercury (thimerosal) from industrial process wastewater, in batch and
      continuously flow through column systems. The organic mercury concentration in
      the process wastewater is about 1123 mg/L due to the thimerosal compound. Four
      commercially available adsorbents are tested for mercury removal and they are:
      Calgon F-400 granular activated carbon (GAC), CB II GAC, Mersorb GAC and an ion
      exchange resin Amberlite GT73. The adsorption capacity of each adsorbent is
      described by the Freundlich isotherm model at pH 3.0, 9.5 and 11.0 in batch
      isotherm experiments. Acidic pH was favorable for thimerosal adsorption onto the
      GACs. Columns-in-series experiments are conducted with 30-180 min empty bed
      contact times (EBCTs). Mercury breakthrough of 30 mg/L occurred after about 47 h
      (96 Bed Volume Fed (BVF)) of operation, and 97 h (197 BVF) with 120 min EBCT and
      180 min EBCT, respectively. Most of the mercury removal is attributed to the 1st
      adsorbent column. Increase in contact time by additional adsorbent columns did
      not lower the effluent mercury concentration below 30 mg/L. However, at a lower
      influent wastewater pH 3, the mercury effluent concentration decreased to less
      than 7 mg/L for up to 90 h of column operation (183 BVF).

PMID- 17459584
TI  - Complex changes in ecto-nucleoside 5'-triphosphate diphosphohydrolase expression
      in hypoxanthine phosphoribosyl transferase deficiency.
AB  - Lesch-Nyhan disease is caused by a deficiency of the purine salvage enzyme,
      hypoxanthine phosphoribosyl transferase (HPRT). The link between HPRT deficiency
      and the neuropsychiatric symptoms is unknown. In rat B103 neuroblastoma cell
      membranes and mouse Neuro2a neuroblastoma cell membranes, nucleoside 5'
      triphosphatase (NTPase) activity is substantially reduced, whereas in fibroblast
      membranes from HPRT knock-out mice, NTPase activity is increased. Candidate genes
      for these NTPase activity changes are ecto-nucleoside 5'-triphosphate
      diphosphohydrolases (NTPDases). Therefore, we studied expression of NTPDases in
      B103 cells, Neuro2a cells and skin fibroblasts by reverse transcriptase
      polymerase chain reaction and restriction enzyme digestion of amplified cDNA
      fragments. In B103 cells, expression of NTPDases 1, 3 and 6 decreased, whereas
      expression of NTPDases 4 and 5 increased in HPRT deficiency. In Neuro2a cells,
      expression of NTPDases 3-6 increased in HPRT deficiency. In fibroblasts, NTPDase
      3 expression decreased, and expression of NTPDases 4-6 increased in HPRT
      deficiency. Collectively, there are complex decreases and increases in NTPDase
      isoform expression in HPRT deficiency that depend on the specific cell type and
      species studied. These changes in NTPDase expression may reflect an
      (insufficient) attempt of cells to compensate for the changes in nucleotide
      metabolism caused by HPRT deficiency.

PMID- 17459585
TI  - Back pain in relation to musculoskeletal disorders in the jaw-face: a matched
      case-control study.
AB  - Back pain and temporomandibular disorders are both common conditions in the
      population with influence on the human motor system, but a possible co-morbidity
      between these conditions has not been fully investigated. The aim of this study
      was to test the hypothesis of an association between long-term back pain and pain
      and/or dysfunction in the jaw-face region. Back pain was defined as pain in the
      neck, shoulders and/or low back. The study-population comprised 96 cases with
      long-term back pain and 192 controls without back pain. We used a screening
      procedure, a questionnaire and a clinical examination of the jaw function. The
      questionnaire focused on location, frequency, duration, intensity and impact on
      daily life of symptoms in the jaw-face and back regions. The analysis was
      conducted on 16 strata, matched by age and sex for case vs. control, using Mantel
      Haenszel estimates of matched odds ratio (OR) and 95% confidence interval (CI) as
      well as the corrected Mantel-Haenszel chi(2) test. The overall prevalence of
      frequent symptoms in the jaw-face region, as reported in the questionnaire, was
      47% among cases and 12% among controls. The difference was statistically
      significant (P<0.0001) with a sevenfold odds ratio (CI: 3.9-13.7). Moderate to
      severe signs from the jaw region were clinically registered among 49% of the
      cases and 17% of the controls (P<0.0001, OR: 5.2, CI: 2.9-9.2). The results
      showed statistically significant associations between long-term back pain and
      musculoskeletal disorders in the jaw-face and indicate co-morbidity between these
      two conditions.

PMID- 17459586
TI  - Mast cell degranulation activates a pain pathway underlying migraine headache.
AB  - Intracranial headaches such as that of migraine are generally accepted to be
      mediated by prolonged activation of meningeal nociceptors but the mechanisms
      responsible for such nociceptor activation are poorly understood. In this study,
      we examined the hypothesis that meningeal nociceptors can be activated locally
      through a neuroimmune interaction with resident mast cells, granulated immune
      cells that densely populate the dura mater. Using in vivo electrophysiological
      single unit recording of meningeal nociceptors in the rat we observed that
      degranulation of dural mast cells using intraperitoneal administration of the
      basic secretagogue agent compound 48/80 (2 mg/kg) induced a prolonged state of
      excitation in meningeal nociceptors. Such activation was accompanied by increased
      expression of the phosphorylated form of the extracellular signal-regulated
      kinase (pERK), an anatomical marker for nociceptor activation. Mast cell-induced
      nociceptor interaction was also associated with downstream activation of the
      spinal trigeminal nucleus as indicated by an increase in c-fos expression. Our
      findings provide evidence linking dural mast cell degranulation to prolonged
      activation of the trigeminal pain pathway believed to underlie intracranial
      headaches such as that of migraine.

PMID- 17459587
TI  - Spatial summation of mechanically evoked muscle pain and painful aftersensations
      in normal subjects and fibromyalgia patients.
AB  - Impulse frequency and number of recruited central neurons are relevant for pain
      encoding and temporal as well as spatial summation of pain (SSP). Whereas SSP of
      heat-induced pain is well characterized, mechanical SSP (MSSP) has been less
      studied. MSSP may be relevant for chronic pain conditions like fibromyalgia (FM)
      and play an important role in the pathogenesis of this chronic pain syndrome. Our
      study was designed to determine MSSP in 12 normal controls (NC) and 11 FM
      subjects. MSSP testing consisted of 5 s suprathreshold pressure-pain stimulations
      of forearm muscles by up to three identical probes (separated by 4 or 8 cm). The
      stimulated areas ranged between 0.79 and 2.37 cm2. The subjects rated the pain
      intensity of mechanical stimuli as well as pain aftersensations. Although MSSP
      increased monotonically in NC and FM subjects, pressure pain and pressure pain
      aftersensations were greater in FM subjects and highly associated with clinical
      pain intensity (r2=.44-.64), suggesting that spatial and temporal summation
      factors may contribute to overall clinical pain. However, despite higher
      experimental pain ratings, the magnitude of MSSP was not statistically different
      between NC and FM subjects. Furthermore, muscle stimuli elicited more MSSP when
      separated by 8 cm than 4 cm and this finding was not different between NC and FM
      subjects. Thus, mechanisms of MSSP were similar for both FM and NC subjects. The
      important role of MSSP for pain encoding suggests that decreasing pain in some
      muscle areas by local anesthetics or other means may improve overall clinical
      pain of FM patients.

PMID- 17459588
TI  - Efficacy of 2,6-dichlorophenol lure to control Dermacentor nitens.
AB  - This study was carried out with the objective of evaluating the efficacy of a 2,6
      dichlorophenol (2,6-DCP) lure to control Dermacentor nitens (Acari: Ixodidae).
      Slow-release formulations of the pheromone formulated with and without
      cypermethrin were prepared. Olfactometer bioassays were used to define the best
      dose of the pheromone and to evaluate the effect of cypermethrin with 2,6-DCP
      attractiveness. Sexually active males were released 15 cm from 2 cmx1 cm pieces
      of polypropylene treated with different odors: 2,6-DCP in a liposphere system
      (1.5, 30 and 300 microg--without cypermethrin and 30 microg--with cypermethrin)
      and 2,6-DCP in hexane (30 microg). The tests were conducted 7 and 15 days after
      the preparation of the odor sources. The percentages of males that oriented, or
      showed directional movement toward the stimulus, and their tracks were recorded.
      Lures (10 cmx2 cm pieces of polypropylene) treated with the best dose of the
      liposphere formulation (30 microg) were prepared. The lures were evaluated in
      horses that had been artificially infested with D. nitens. The horses' ears were
      infested with 3000 D. nitens larvae per ear, once weekly for 4 weeks. The animals
      were divided into three groups: control, 2,6-DCP and 2,6-DCP+cypermethrin. On day
      0, the lures of their respective treatments were attached to the horses' napes.
      From days 6 to 20 after attachment, female ticks of 4 mm or over in length were
      counted on the ears, every 2 or 3 days. Olfactometer analysis showed higher
      orientation to 30 microg dose and more prolonged release of the pheromone in the
      liposphere formulation than in hexane; cypermethrin did not interfere with the
      attractive effect of the pheromone. The lures were efficient in the first 10 days
      after attachment, when the mean number of females was higher in the control group
      (24.9) than in 2,6-DCP and cypermethrin (5.4), and 2,6-DCP (9.2) groups. After
      that period the number of females was similar in the control and treated groups.
      These results indicate that 2,6-DCP lures used in a liposphere formulation can
      control D. nitens for at least 10 days by preventing its copulation. However,
      further evaluation of longer-term pheromone release under natural conditions is
      needed in order to validate this kind of control. In addition, the use of extra
      lures on the horse's tail may help to control populations on the hindquarters.

PMID- 17459589
TI  - Population dynamics and maturation cycle of Camallanus cotti (Nematoda:
      Camallanidae) in the Chinese hooksnout carp Opsariichthys bidens (Osteichthyes:
      Cyprinidae) from a reservoir in China.
AB  - The seasonal population dynamics and maturation cycle of the nematode Camallanus
      cotti in the posterior intestine of Chinese hooksnout carp Opsariichthys bidens
      have been studied in the Danjiangkou Reservoir of the Hubei Province in central
      China from September 2004 to November 2005. The overall prevalence, mean
      abundance and intensity of C. cotti among fish sampled (n=700 fish) were 47%,
      2.29+/-12.38 (+/-S.D.) and 1-307 (average 4.89+/-17.74), respectively. The
      overall sexual ratio of female to male nematodes (excluding L3 and L4 juveniles)
      was 1.17:1. Statistical results showed weakly positive correlations between fish
      length and the number of nematodes per host. The dynamics of infection of the
      nematode exhibited significant seasonal pattern in changes in mean abundance. A
      similar pattern was found for changes in nematode prevalence, although this was
      not statistically significant. Higher levels of infection were observed among
      fish sampled in summer months and the lower in the winter. Neither the prevalence
      nor the abundance of the parasite was significantly different between male and
      female hosts. The pattern of frequency distribution of the parasite in the host
      was found to be over-dispersed throughout the sampling period. In addition,
      studies on the development and maturation of the parasite in O. bidens revealed
      that development (maturation), recruitment of the next generation, and
      reproduction may be continuous year-round, although reproduction may peak during
      the winter.

PMID- 17459590
TI  - Expression and characterization of cytochrome P450 2X1 in channel catfish
      (Ictalurus punctatus).
AB  - Previous studies in channel catfish identified a novel cDNA encoding the
      cytochrome P450 isoform, CYP2X1. To characterize the substrate specificity of
      CYP2X1, the 57 kDa protein was expressed in Sf9 cells. Microsomes from Sf9 cells
      transfected with CYP2X1 demonstrated a maximum carbon monoxide-reduced difference
      spectrum at 450 nm and catalyzed aminopyrine and benzphetamine demethylase
      activity with catalytic efficiency (Vmax/Km) values of 0.82 pmol/nmol P450/min
      and 4.39 pmol/nmol P450/min, respectively. However, enzymatic activity was not
      observed following incubation with p-nitrophenol, benzyloxyresorufin or
      pentoxyresorufin. Expression of CYP2X1 transcription was significantly elevated
      in the gills and liver relative to that detected in brain, kidney and heart. In
      the brain, liver and heart, intraperitoneal injections with clofibric acid,
      ethanol, pyridine and rifampin failed to alter expression of CYP2X1 mRNA. In
      kidney, pyridine significantly suppressed the expression of CYP2X1 transcription
      (p < or = 0.05). These results indicate CYP2X1 displays minimal catalytic
      activities consistent with other piscine CYP2 isoforms, and unique tissue
      expression and regulation patterns in juvenile channel catfish.

PMID- 17459591
TI  - Age-dependent expression of VEGF isoforms and receptors in the rabbit anterior
      cruciate ligament.
AB  - Vascular endothelial growth factor (VEGF) gene gives rise to several distinct
      isoforms of VEGF. Those isoforms differ in biochemical and biological properties,
      and it has been reported that their expression patterns are tissue and age
      specific as well. We investigated the expression levels of VEGF isoforms
      (VEGF121, VEGF165, VEGF183, VEGF189) and its receptors (VEGFR-1, flt-1 and VEGFR
      2, flk-1/KDR) in the anterior cruciate ligament (ACL) of 2- to 3-week-, 2-month-,
      and 18-month-old New Zealand White rabbits using Sybr green Real-Time RT-PCR.
      VEGF isoforms and both receptors were expressed in the ACL at all investigated
      ages. VEGF121 was found to be the most abundant isoform at the ages under
      investigation, followed by VEGF165, VEGF189 and VEGF183. All isoforms showed
      decreased expression levels with age, however the larger membrane bound isoforms,
      VEGF183 and VEGF189, showed the most striking age-associated decrease in
      expression level. VEGFR-1 expression levels increased with age, while the
      expression level of VEGFR-2 expression was highest at 2-3 weeks and was
      significantly lower at 2 and 18 months of age. Distinct age-associated
      differences in the expression level of VEGF isoforms as well as their receptors
      suggest differential physiological functions during development, maturation and
      ageing of the ACL.

PMID- 17459592
TI  - Temporal profile of subventricular zone progenitor cell migration following
      quinolinic acid-induced striatal cell loss.
AB  - A number of studies have demonstrated directed migration of neural progenitor
      cells to sites of brain injury and disease, however a detailed examination of
      when a cell is "born" in relation to injury induction and the migratory response
      of that cell has not previously been determined. This study therefore examined
      the temporal correlation between progenitor cell proliferation ("birth") and
      neuroblast migratory response into the damaged striatum following quinolinic acid
      (QA) lesioning of the adult rat striatum. Retroviral labeling of subventricular
      zone (SVZ)-derived progenitor cells demonstrated that cell loss in the QA
      lesioned striatum increased progenitor cell migration through the rostral
      migratory stream (RMS) for up to 30 days. In addition, a population of dividing
      cells originating from the SVZ generated doublecortin positive neuroblasts that
      migrated into the damaged striatum in response to cell loss invoked by the QA
      lesion. Quantification of bromodeoxyuridine (BrdU)-labeled cells co-expressing
      doublecortin revealed that the majority of cells present in the damaged striatum
      were generated from progenitor cells dividing within 2 days either prior to or
      following the QA lesion. In contrast, cells dividing 2 or more days following QA
      lesioning, migrated into the striatum and exhibited a glial phenotype. These
      results demonstrate that directed migration of SVZ-derived cells and neuroblast
      differentiation in response to QA lesioning of the striatum is acute and
      transient. We propose this is predominantly due to a reduced capacity over time
      for newly generated neuroblasts to respond to the lesioned environment due to a
      loss or inhibition of migratory cues.

PMID- 17459593
TI  - Are event-related potential components generated by phase resetting of brain
      oscillations? A critical discussion.
AB  - The event-related potential (ERP) is one of the most popular measures in human
      cognitive neuroscience. During the last few years there has been a debate about
      the neural fundamentals of ERPs. Two models have been proposed: The evoked model
      states that additive evoked responses which are completely independent of ongoing
      background electroencephalogram generate the ERP. On the other hand the phase
      reset model suggests a resetting of ongoing brain oscillations to be the neural
      generator of ERPs. Here, evidence for either of the two models is presented and
      validated, and their possible impact on cognitive neuroscience is discussed. In
      addition, future prospects on this field of research are presented.

PMID- 17459594
TI  - Neuroprotective role of the innate immune system by microglia.
AB  - Innate immunity is a rapid series of reactions to pathogens, cell injuries and
      toxic proteins. A key component of this natural response is the production of
      inflammatory mediators by resident microglia and infiltrating macrophages. There
      is accumulating evidence that inflammation contributes to acute injuries and more
      chronic CNS diseases, though other studies have shown that inhibition of
      microglia is, in contrast, associated with more damages or less repair. The
      controversies regarding the neuroprotective and neurodegenerative properties of
      microglia may depend on the experimental approaches. Neurotoxic substances are
      frequently used to produce animal models of acute injuries or diseases and they
      may activate microglia either directly or indirectly by their ability to cause
      neuronal death and demyelination. Whether microglia and the immune response play
      a direct role in such processes still remains an open question. On the other
      hand, there are data supporting the role of resident microglia and those derived
      from the bone marrow in the stimulation of myelin repair, removal of toxic
      proteins from the CNS and the prevention of neurodegeneration in chronic brain
      diseases. The ability of glucocorticoids to provide a negative feedback on
      nuclear factor kappa B pathways in microglia may be a determinant mechanism
      underlying the ultimate fate of the inflammatory response in the CNS. This review
      presents new concepts regarding the neuroprotective role of the innate immune
      response in the brain and how microglia can be directed to improve recovery after
      injuries and prevent/delay neurodegeneration.

PMID- 17459595
TI  - Neuroprotective effects of estradiol in hippocampal neurons and glia of middle
      age mice.
AB  - During aging the hippocampus experiences structural, molecular, and functional
      alterations. Protection from age-related disorders is provided by several
      factors, including estrogens. Since aging defects start at middle age, we studied
      if 17 beta-estradiol (E(2)) protected the hippocampus at this age period. Middle
      age (10-12 month old) male C57Bl/6 mice were implanted sc with E(2) (15 microg)
      or cholesterol pellets. Ten days afterwards they received bromodeoxyuridine
      (BrdU) 4 and 2h before killing to study cell proliferation in the dentate gyrus
      (DG). A pronounced depletion of BrdU+cells in the DG was found in cholesterol
      treated middle age mice, accompanied by astrocytosis, and by neuronal loss in the
      hilus. Middle age mice receiving E(2) showed increased number of BrdU+cells while
      the other parameters were remarkably attenuated. When steroid treatment was
      prolonged for 2 months to study migration of cells in the granular layer of the
      DG, cell migration was unaffected by E(2). However, E(2)-treated middle age mice
      presented higher cell density and increased staining for doublecortin, a marker
      for differentiating neurons. Thus, from the three basic steps of adult
      neurogenesis (proliferation, migration, and differentiation), E(2) stimulated
      progenitor proliferation - even after long exposure to E(2) studied by Ki67
      immunocytochemistry - and differentiation towards a neuronal lineage. This
      result, in conjunction with recovery from other aging indicators as increased
      deposits of the aging pigment lipofuscin in DG cells, loss of hilar neurons and
      astrocytosis supports a wide range protection of hippocampal function of middle
      age mice by estrogenic hormones.

PMID- 17459596
TI  - Induction of DNA damage, alteration of DNA repair and transcriptional activation
      by stress hormones.
AB  - Stress is associated with increased production of sympathetic and other adrenal
      hormones. Epinephrine (E), norepinephrine (NE) and cortisol are produced during
      psychological stress and may affect many cells directly. These effects may be
      transient (e.g. heart rate, immune cell trafficking) or they can have more long
      lasting consequences, such as permanent DNA damage which may result in increased
      cell transformation and/or tumorigenicity. Here, the molecular effects of short
      term in vitro exposure of these stress hormones were analyzed on murine 3T3 cells
      by measuring effects on DNA damage and repair, cell transformation and changes in
      mRNA expression of genes specifically involved in DNA damage signaling pathways.
      Short-term exposure (<30 min) to physiological concentrations of either cortisol,
      NE or E induced at least five-fold increases in DNA damage in treated cells
      compared to untreated controls. Pre-treatment with blocking agents such as the
      glucocorticoid receptor antagonist RU486, or the beta-adrenergic receptor
      antagonist propranolol, eliminated this increase in damage. Both cortisol and NE
      interfered with repair of DNA damage in cells exposed to UV and resulted in an
      increase in the transformed phenotype. In contrast, E had none of these effects
      on 3T3 cells. Stress hormones had no significant effects on cell cycle
      regulation. Targeted gene arrays showed that cortisol, NE and E modulated the
      transcription of 21, 14 and 18 genes, respectively. These genes were directly
      related to DNA damage signaling pathways, and included up-regulation of DNA
      damage sensors Chk1 and Chk2, and the proto-oncogene CDC25A, which is involved in
      cell cycle delay following DNA damage. Taken together, these data show that
      stress hormones can increase DNA damage and transformation and alter
      transcriptional regulation of the cell cycle.

PMID- 17459597
TI  - Is stress a trigger factor for migraine?
AB  - BACKGROUND: Although mental stress is commonly considered to be an important
      trigger factor for migraine, experimental evidence for this belief is yet
      lacking. OBJECTIVE: To study the temporal relationship between changes in stress
      related parameters (both subjective and objective) and the onset of a migraine
      attack. METHODS: This was a prospective, ambulatory study in 17 migraine
      patients. We assessed changes in perceived stress and objective biological
      measures for stress (saliva cortisol, heart rate average [HRA], and heart rate
      variability [low-frequency power and high-frequency power]) over 4 days prior to
      the onset of spontaneous migraine attacks. Analyses were repeated for subgroups
      of patients according to whether or not they felt their migraine to be triggered
      by stress. RESULTS: There were no significant temporal changes over time for the
      whole group in perceived stress (p=0.50), morning cortisol (p=0.73), evening
      cortisol (p=0.55), HRA (p=0.83), low-frequency power (p=0.99) and high-frequency
      power (p=0.97) prior to or during an attack. Post hoc analysis of the subgroup of
      nine stress-sensitive patients who felt that >2/3 of their migraine attacks were
      triggered by psychosocial stress, revealed an increase for perceived stress
      (p=0.04) but no changes in objective stress response measures. At baseline, this
      group also showed higher scores on the Penn State Worry Questionnaire (p=0.003)
      and the Cohen Perceived Stress Scale (p=0.001) compared to non-stress-sensitive
      patients. CONCLUSIONS: Although stress-sensitive patients, in contrast to non
      stress-sensitive patients, may perceive more stress in the days before an
      impending migraine attack, we failed to detect any objective evidence for a
      biological stress response before or during migraine attacks.

PMID- 17459598
TI  - Do reports of consciousness during cardiac arrest hold the key to discovering the
      nature of consciousness?
AB  - Perhaps the biggest challenge facing neuroscience at the dawn of the 21st century
      is understanding the relationship between mind, consciousness and the brain.
      Editorials in recent years have highlighted the difficulties faced by cognitive
      neuroscience in attempting to answer questions regarding the nature, as well as
      the mechanism by which subjective experiences and our sense of consciousness may
      arise through neuronal processes. Current scientific views regarding the origin
      of consciousness vary widely and range from an 'epiphenomenon' arising from
      neuronal networks, to neuronal quantum processes, to a separate undiscovered
      scientific entity. Although there has been a lack of experimental studies to test
      these theories, recent studies have indicated that the study of the human mind
      during cardiac arrest may hold the key to solving the mystery of consciousness.
      Four published prospective studies of cardiac arrest survivors have demonstrated
      that paradoxically human mind and consciousness may continue to function during
      cardiac arrest. This is despite the well demonstrated finding that cerebral
      functioning as measured by electrical activity of the brain ceases during cardiac
      arrest, thus raising the possibility that human mind and consciousness may
      continue to function in the absence of brain function. In this article the broad
      theories for the causation of consciousness are reviewed as well as a novel
      method to study consciousness during cardiac arrest. This may provide a unique
      experimental method to determine the nature of human mind and consciousness as
      well as its relationship with the brain.

PMID- 17459599
TI  - Can neuroimaging reduce social stigma in schizophrenia?

PMID- 17459600
TI  - ABCG1--a potential therapeutic target for atherosclerosis.
AB  - Cholesterol efflux from macrophage foam cells, the initial step of reverse
      cholesterol transport, is assumed to be the most relevant step with respect to
      atherosclerosis. As one of the ATP-binding cassette transporter (ABC) family
      members, ABCG1 plays a critical role in the process of cholesterol efflux. It has
      been recently identified to export cellular cholesterol to large HDL particles.
      For mature HDL constitutes the bulk of the plasma HDL, ABCG1 is responsible for
      the majority of the cholesterol efflux from macrophage foam cells to serum.
      Overexpression of ABCG1 improves HDL function through stimulating cholesterol
      export. Therefore, it could be hypothesized that ABCG1 would be a new target for
      the treatment of atherosclerosis.

PMID- 17459601
TI  - Addison's disease and the regulation of potassium: the role of insulin and
      aldosterone.
AB  - It is proposed that insulin has a cardinal role in the regulation of serum
      potassium levels in man, which may be of greater importance than the effect of
      insulin on glucose metabolism. Although the first described action of insulin was
      on glucose transport, it is a hormone with many functions some of which may
      operate in a metabolic hierarchy depending on the relative importance of the
      action required. Insulin also promotes the transport of potassium ions from the
      extracellular space to the intracellular space and it is suggested that there are
      occasions where this action may take place at the expense of glucose regulation.
      In metabolic terms, tight control of serum potassium is of greater importance
      than precise control of serum glucose, because quite small variations in serum
      potassium may cause death whereas wide variations in serum glucose may be
      tolerated. Serum potassium levels generally remain very stable despite large
      daily variations in potassium intake. It follows that potassium control
      mechanisms must be of outstanding efficiency as serious disturbances of potassium
      balance are relatively uncommon. 'Nature makes experiments on Man': shadowy but
      important physiological mechanisms that may almost be taken for granted in normal
      health are often brightly illuminated by unusual pathological conditions. This
      paper describes two remarkable patients who presented with extreme hyperkalaemia.
      This condition was the result of simultaneous insulin and aldosterone deficiency
      occurring because of concomitant diabetes and Addison's disease. Other medical
      conditions with disturbances in aldosterone, insulin and potassium control will
      be referred to in support of the hypothesis that insulin secretion is central to
      potassium regulation. This hypothesis explains the secondary disturbances in
      glucose metabolism that occurs in clinical situations where the primary problem
      is perturbation of potassium regulation.

PMID- 17459602
TI  - A new concept of melanocytic neoplasia pathogenesis based on the phenotype of
      common acquired nevi.
AB  - Common melanocytic nevi are ubiquitous lesions which in some cases constitute a
      risk factor for the development of melanoma. To date, despite long term research
      there are no known molecular hallmarks for nevus development. We have observed
      that common acquired nevi excised from the same individual share remarkable
      similarity in their microscopic appearance and in the immunohistochemical
      expression of E-cadherin. Based on these observations, we hypothesize that all
      melanocytes are genetically similar in the same individual and changes
      predisposing to neoplasia are a global melanocytic event characteristic for each
      person and propose a microgenomics/proteomics approach to test this hypothesis.

PMID- 17459603
TI  - Tumor expression of major vault protein is an adverse prognostic factor for
      radiotherapy outcome in oropharyngeal carcinoma.
AB  - PURPOSE: Vaults are multi-subunit structures that may be involved in nucleo
      cytoplasmic transport, with the major vault protein (MVP or lung resistance
      related protein [LRP]) being the main component. The MVP gene is located on
      chromosome 16 close to the multidrug resistance-associated protein and protein
      kinase c-beta genes. The role of MVP in cancer drug resistance has been
      demonstrated in various cell lines as well as in ovarian carcinomas and acute
      myeloid leukemia, but nothing is known about its possible role in radiation
      resistance. Our aim was to examine this in head-and-neck squamous cell carcinoma
      (HNSCC). METHODS AND MATERIALS: Archived biopsy material was obtained for 78
      patients with squamous cell carcinoma of the oropharynx who received primary
      radiotherapy with curative intent. Immunohistochemistry was used to detect MVP
      expression. Locoregional failure and cancer-specific survival were estimated
      using cumulative incidence and Cox multivariate analyses. RESULTS: In a
      univariate and multivariate analysis, MVP expression was strongly associated with
      both locoregional failure and cancer-specific survival. After adjustment for
      disease site, stage, grade, anemia, smoking, alcohol, gender, and age, the
      estimated hazard ratio for high MVP (2/3) compared with low (0/1) was 4.98 (95%
      confidence interval, 2.17-11.42; p = 0.0002) for locoregional failure and 4.28
      (95% confidence interval, 1.85-9.95; p = 0.001) for cancer-specific mortality.
      CONCLUSION: These data are the first to show that MVP may be a useful prognostic
      marker associated with radiotherapy resistance in a subgroup of patients with
      HNSCC.

PMID- 17459604
TI  - High dose-rate intracavitary brachytherapy for cervical carcinomas with lower
      vaginal infiltration.
AB  - PURPOSE: This report presents the clinical applications of an automated treatment
      planning program of high-dose-rate intracavitary brachytherapy (HDR-ICBT) for
      advanced uterine cervical cancer infiltrating the parametrium and the lower
      vagina. METHODS AND MATERIALS: We adopted HDR-ICBT under optimized dose
      distribution for 22 cervical cancer patients with tumor infiltration of the lower
      half of the vagina. All patients had squamous cell carcinoma with International
      Federation of Gynecology and Obstetrics clinical stages IIB-IVA. After whole
      pelvic external beam irradiation with a median dose of 30.6 Gy, a conventional
      ICBT was applied as "pear-shaped" isodose curve. Then 3-4 more sessions per week
      of this new method of ICBT were performed. With a simple determination of the
      treatment volume, the cervix-parametrium, and the lower vagina were covered
      automatically and simultaneously by this program, that was designated as "utero
      vaginal brachytherapy". The mean follow-up period was 87.4 months (range, 51.8
      147.9 months). RESULTS: Isodose curve for this program was "galaxy-shaped". Five
      year local-progression-free survival and overall survival rates were 90.7% and
      81.8%, respectively. Among those patients with late complications higher than
      Grade 2 Radiation Therapy Oncology Group/European Organization for Research and
      Treatment of Cancer morbidity score, only one (4.5%) developed severe proctitis.
      CONCLUSIONS: Because of the favorable treatment outcomes, this treatment-planning
      program with a simplified target-volume based dosimetry was proposed for cervical
      cancer with lower vaginal infiltration.

PMID- 17459605
TI  - Intensity-modulated radiotherapy using implanted fiducial markers with daily
      portal imaging: assessment of prostate organ motion.
AB  - PURPOSE: To assess our single institutional experience with daily localization,
      using fiducials for prostate radiotherapy. METHODS AND MATERIALS: From January
      2004 to September 2005, 33 patients were treated with 1,097 intensity-modulated
      radiation treatments, using three implanted fiducials. Daily portal images were
      obtained before treatments. Shifts were made for deviations > or =3 mm in the
      left-right (LR), superior-inferior (SI), and anterior-posterior (AP) dimensions.
      RESULTS: Of 1,097 treatments, 987 (90%) required shifts. Shifts were made in the
      LR, SI, and AP dimensions in 51%, 67%, and 58% of treatments, respectively. In
      the LR dimension, the median distance shifted was 5 mm. Of 739 shifts in the SI
      dimension, 73% were in the superior direction for a median distance of 6 mm, and
      27% were shifted inferiorly for a median distance of 5 mm. The majority of shifts
      in the AP dimension were in the anterior direction (87%). Median distances
      shifted in the anterior and posterior directions were 5 mm and 4 mm,
      respectively. The median percentage of treatments requiring shifts per patient
      was 93% (range, 57-100%). Median deviations in the LR, SI, and AP dimensions were
      3 mm, 4 mm, and 3 mm, respectively. Deviations in the SI and AP dimensions were
      more often in the superior rather than inferior (60% vs. 29%) and in the anterior
      rather than posterior (70% vs. 16%) directions. CONCLUSIONS: Interfraction
      prostate motion is significant. Daily portal imaging with implanted fiducials
      improves localization of the prostate, and is necessary for the reduction of
      treatment margins.

PMID- 17459606
TI  - Radiotherapy after prostatectomy: improved biochemical relapse-free survival with
      whole pelvic compared with prostate bed only for high-risk patients.
AB  - PURPOSE: To compare the biochemical relapse-free survival (bRFS) among patients
      receiving whole pelvic radiotherapy (WPRT) vs. prostate bed RT (PBRT) after
      radical prostatectomy. METHODS AND MATERIALS: Between 1985 and 2005, 160 patients
      underwent adjuvant or salvage RT after radical prostatectomy. A short course of
      total androgen suppression was also given concurrently to 87 patients. Of the 160
      patients, 114 were considered at high risk of lymph node involvement because they
      had a pathologic Gleason score of >/=8, a preoperative prostate-specific antigen
      level >20 ng/mL, seminal vesicle or prostate capsule involvement, or pathologic
      lymph node involvement. Of this group, 72 underwent WPRT and 42 underwent PBRT.
      The median follow-up was >5 years for all patient subsets. Kaplan-Meier and Cox
      proportional hazards multivariate analyses were performed for all clinical,
      pathologic, and treatment factors predicting for bRFS. RESULTS: Whole pelvic RT
      resulted in superior bRFS compared with PBRT (p = 0.03). The advantage of WPRT
      was limited to high-risk patients, with a 5-year bRFS rate of 47% (95% confidence
      interval, 35-59%) after WPRT vs. 21% (95% confidence interval, 8-35%) after PBRT
      (p = 0.008). For low-risk patients, no difference (p = 0.9) was found. On
      multivariate analysis, only WPRT (p = 0.02) and a preoperative prostate-specific
      antigen level <1.0 ng/mL (p = 0.002) were significantly associated with bRFS. The
      benefit from total androgen suppression with postoperative RT was only observed
      when given concurrently with WPRT (p = 0.04) and not with PBRT (p = 0.4).
      CONCLUSION: The results of our study have indicated that WPRT confers superior
      bRFS compared with PBRT for high-risk patients receiving adjuvant or salvage RT
      after radical prostatectomy. This advantage was observed only with concurrent
      TAS. These results are analogous to the benefit from WPRT seen in the Radiation
      Therapy Oncology Group 94-13 study.

PMID- 17459607
TI  - Phase I/II clinical trial of carbon ion radiotherapy for malignant gliomas:
      combined X-ray radiotherapy, chemotherapy, and carbon ion radiotherapy.
AB  - PURPOSE: To report the results of a Phase I/II clinical trial for patients with
      malignant gliomas, treated with combined X-ray radiotherapy (XRT), chemotherapy,
      and carbon ion radiotherapy (CRT). METHODS AND MATERIALS: Between October 1994
      and February 2002, 48 patients with histologically confirmed malignant gliomas
      (16 anaplastic astrocytoma (AA) and 32 glioblastoma multiforme (GBM) were
      enrolled in a Phase I/II clinical study. The treatment involved the application
      of 50 Gy/25 fractions/5 weeks of XRT, followed by CRT at 8 fractions/2 weeks.
      Nimustine hydrochloride (ACNU) were administered at a dose of 100 mg/m(2)
      concurrently in weeks 1, 4, or 5 of XRT. The carbon ion dose was increased from
      16.8 to 24.8 Gray equivalent (GyE) in 10% incremental steps (16.8, 18.4, 20.0,
      22.4, and 24.8 GyE, respectively). RESULTS: There was no Grade 3 or higher acute
      reaction in the brain. The late reactions included four cases of Grade 2 brain
      morbidity and four cases of Grade 2 brain reaction among 48 cases. The median
      survival time (MST) of AA patients was 35 months and that of GBM patients 17
      months (p = 0.0035). The median progression-free survival and MST of GBM showed 4
      and 7 months for the low-dose group, 7 and 19 months for the middle-dose group,
      and 14 and 26 months for the high-dose group. CONCLUSION: The results of combined
      therapy using XRT, ACNU chemotherapy, and CRT showed the potential efficacy of
      CRT for malignant gliomas in terms of the improved survival rate in those
      patients who received higher carbon doses.

PMID- 17459608
TI  - The impact of dose escalation on secondary cancer risk after radiotherapy of
      prostate cancer.
AB  - PURPOSE: To estimate secondary cancer risk due to dose escalation in patients
      treated for prostatic carcinoma with three-dimensional conformal radiotherapy (3D
      CRT), intensity-modulated RT (IMRT), and spot-scanned proton RT. METHODS AND
      MATERIALS: The organ equivalent dose (OED) concept with a linear-exponential, a
      plateau, and a linear dose-response curve was applied to dose distributions of 23
      patients who received RT of prostate cancer. Conformal RT was used in 7 patients,
      8 patients received IMRT with 6- and 15-MV photons, and 8 patients were treated
      with spot-scanned protons. We applied target doses ranging from 70 Gy to 100 Gy.
      Cancer risk was estimated as a function of target dose and tumor control
      probability. RESULTS: At a 100-Gy target dose the secondary cancer risk relative
      to the 3D treatment plan at 70 Gy was +18.4% (15.0% for a plateau model, 22.3%
      for a linear model) for the 6-MV IMRT plan, +25.3% (17.0%, 14.1%) for the 15-MV
      IMRT plan, and -40.7% (-41.3%, -40.0%) for the spot-scanned protons. The
      increasing risk of developing a radiation-associated malignancy after RT with
      increasing dose was balanced by the enhanced cure rates at a larger dose.
      CONCLUSIONS: Cancer risk after dose escalation for prostate RT is expected to be
      equal to or lower than for conventional 3D treatment at 70 Gy, independent of
      treatment modality or dose-response model. Spot-scanned protons are the treatment
      of choice for dose escalation because this therapy can halve the risk of
      secondary cancers.

PMID- 17459609
TI  - Carcinomas of the paranasal sinuses and nasal cavity treated with radiotherapy at
      a single institution over five decades: are we making improvement?
AB  - PURPOSE: To compare clinical outcomes of patients with carcinomas of the
      paranasal sinuses and nasal cavity according to decade of radiation treatment.
      METHODS AND MATERIALS: Between 1960 and 2005, 127 patients with sinonasal
      carcinoma underwent radiotherapy with planning and delivery techniques available
      at the time of treatment. Fifty-nine patients were treated by conventional
      radiotherapy; 45 patients by three-dimensional conformal radiotherapy; and 23
      patients by intensity-modulated radiotherapy. Eighty-two patients (65%) were
      treated with radiotherapy after gross total tumor resection. Nineteen patients
      (15%) received chemotherapy. The most common histology was squamous cell
      carcinoma (83 patients). RESULTS: The 5-year estimates of overall survival, local
      control, and disease-free survival for the entire patient population were 52%,
      62%, and 54%, respectively. There were no significant differences in any of these
      endpoints with respect to decade of treatment or radiotherapy technique (p >
      0.05, for all). The 5-year overall survival rate for patients treated in the
      1960s, 1970s, 1980s, 1990s, and 2000s was 46%, 56%, 51%, 53%, and 49%,
      respectively (p = 0.23). The observed incidence of severe (Grade 3 or 4) late
      toxicity was 53%, 45%, 39%, 28%, and 16% among patients treated in the 1960s,
      1970s, 1980s, 1990s, and 2000s, respectively (p = 0.01). CONCLUSION: Although we
      did not detect improvements in disease control or overall survival for patients
      treated over time, the incidence of complications has significantly declined,
      thereby resulting in an improved therapeutic ratio for patients with carcinomas
      of the paranasal sinuses and nasal cavity.

PMID- 17459610
TI  - A study of image-guided intensity-modulated radiotherapy with fiducials for
      localized prostate cancer including pelvic lymph nodes.
AB  - PURPOSE: To study the impact on nodal coverage and dose to fixed organs at risk
      when using daily fiducial localization of the prostate to deliver intensity
      modulated radiotherapy (IMRT). METHODS AND MATERIALS: Five patients with prostate
      cancer in whom prostate and pelvic nodes were irradiated with IMRT were studied.
      Dose was prescribed such that 95% of the prostate planning target volume (PTV)
      and 90% of the nodal PTV were covered. Random and systematic prostate
      displacements in the anterior-posterior, superior-inferior, and left-right
      directions were simulated to shift the original isocenter of the IMRT plan. The
      composite dose during the course of treatment was calculated. RESULTS: Compared
      with a static setup, simulating random shifts reduced dose by less than 1.5% for
      nodal hotspot (i.e., dose to 1 cm(3)), by less than 1% for the 90% nodal PTV
      coverage, and by less than 0.5% for the nodal mean dose. Bowel and femoral head
      hotspots were reduced by less than 1.5% and 2%, respectively. A 10-mm systematic
      offset reduced nodal coverage by up to 10%. CONCLUSION: The use of prostate
      fiducials for daily localization during IMRT treatment results in negligible
      changes in dose coverage of pelvic nodes or normal tissue sparing in the absence
      of a significant systematic offset. This offers a simple and practical solution
      to the problem of image-guided radiotherapy for prostate cancer when including
      pelvic nodes.

PMID- 17459611
TI  - Do trauma history and PTSD symptoms influence addiction relapse context?
AB  - Exposure to traumatic events is common among individuals with substance use
      disorders (SUD), although not all go on to develop PTSD. We compared SUD
      treatment outcomes and relapse features in three groups of male veterans
      receiving SUD treatment: (1) those without trauma exposure (SUD-only; n=68), (2)
      those with PTSD (SUD-PTSD; n=32), and (3) those with trauma exposure but no PTSD
      (SUD-trauma; n=34). Veterans were assessed regarding psychiatric symptoms,
      substance use, and relapse features quarterly for 1 year. The groups did not
      differ on length of abstinence, relapse prevalence or severity. SUD-PTSD and SUD
      trauma reported more depression, anxiety, PTSD, and total psychiatric symptoms
      prior to relapse than SUD-only. SUD-PTSD and SUD-trauma also endorsed more PTSD,
      and total symptoms following relapse than SUD-only. PTSD symptoms were associated
      with greater risk of relapse in intrapersonal and negative physiological
      contexts. Understanding relapse contexts for those experiencing PTSD symptoms can
      help us to understand one mechanism whereby those with both PTSD and SUD have a
      poorer clinical course.

PMID- 17459612
TI  - Glucoamylase gene, vldI, is linked to validamycin biosynthesis in Streptomyces
      hygroscopicus var. limoneus, and vldADEFG confers validamycin production in
      Streptomyces lividans, revealing the role of VldE in glucose attachment.
AB  - The validamycin biosynthetic gene cluster in Streptomyces hygroscopicus var.
      limoneus contains vldI, the gene encoding a glucoamylase (1,4-alpha-D-glucan
      glucohydrolase). The knock-out of vldI (vldI::neo) reduced the yield of
      validamycin-A, thus indicating that VldI contributes to validamycin-A
      productivity by supplying glucose with the hydrolysis of 1,4-alpha-D-glucan(s).
      Promoter-probe assays employing xylE fusions indicated that the transcription of
      vldI correlates to those of other biosynthetic genes, which are organized with
      two divergently arranged vldABC and vldDEFGH sets. These results reveal that the
      contiguous region covering nine genes of vldABCDEFGHI represents the core of the
      validamycin biosynthetic cluster. After confirming that genes vldABCDEFGH confer
      validamycin production ability to Streptomyces lividans, genes vldBCHI were
      eliminated from the expression construct and the remaining genes, vldADEFG, were
      tested for the ability to confer validamycin-A production to S. lividans. Ion
      exchange chromatographic purification and a subsequent HPLC analysis confirmed
      that S. lividans/vldADEFG yielded a 75 microg/l of validamycin-A, showing that
      the validamycin pathway involves a single NDP-sugar glycosyltransferase reaction.
      It was also demonstrated that VldE is capable of coupling validoxylamine-A and
      UDP-glucose to generate validamycin-A. The proposal that VldADEFG catalyze the
      biosynthesis of validamycin-A from sedo-heptulose 7-phosphate and UDP-glucose and
      include a N-bridge-forming catalyst will serve as a guideline for future
      biochemical studies and a platform to explore this m-C7N cyclitol pathway for
      biotechnological applications.

PMID- 17459613
TI  - Evidence for recent horizontal transfer of gypsy-homologous LTR-retrotransposon
      gtwin into Drosophila erecta followed by its amplification with multiple
      aberrations.
AB  - Long terminal repeat (LTR) retrotransposon gtwin was initially discovered in
      silico, and then it was isolated as gypsy-homologous sequence from Drosophila
      melanogaster strain, G32. The presence of ORF3 suggests, that gtwin, like gypsy,
      may be an endogenous retrovirus, which can leave the cell and infect another one.
      Therefore, in this study we decided to investigate the distribution of gtwin in
      different species of the melanogaster subgroup in order to find out whether gtwin
      can be transferred horizontally as well as vertically. Gtwin was found in all 9
      species of this subgroup, hence it seems to have inhabited the host genomes for a
      long time. In addition, we have shown that in the Drosophila erecta genome two
      gtwin families are present. The first one has 93% of identity to D. melanogaster
      element and is likely to be a descendant of gtwin that existed in Drosophila
      before the divergence of the melanogaster subgroup species. The other one has
      >99% of identity to D. melanogaster gtwin. The most reasonable explanation is
      that this element has been recently horizontally transferred between D.
      melanogaster and D. erecta. The number and variety of gtwin copies from the
      "infectious" family suggest that after the horizontal transfer into D. erecta
      genome, gtwin underwent amplification and aberrations, leading to the rise of its
      diverse variants.

PMID- 17459615
TI  - Efficient and cell specific knock-down of gene function in targeted C. elegans
      neurons.
AB  - The nematode C. elegans has become an important model for understanding how genes
      influence behavior. However, in this organism the available approaches for
      identifying the neuron(s) where the function of a gene is required for a given
      behavioral trait are time consuming and restricted to non essential genes for
      which mutants are available. We describe a simple reverse genetics approach for
      reducing, in chosen C. elegans neurons, the function of genes. The method is
      based on the expression, under cell specific promoters, of sense and antisense
      RNA corresponding to a gene of interest. By targeting the genes osm-10, osm-6 and
      the Green Fluorescent Protein gene, gfp, we show that this approach leads to
      efficient, heritable and cell autonomous knock-downs of gene function, even in
      neurons usually refractory to classic RNA interference (RNAi). By targeting the
      essential and ubiquitously expressed gene, gpb-1, which encodes a G protein beta
      subunit, we identify for the first time two distinct sets of neurons in which the
      function of gpb-1 is required to regulate two distinct behaviors: egg-laying and
      avoidance of repellents. The cell specific knock-downs obtained with this
      approach provide information that is complementary to that provided by the cell
      specific rescue of loss-of-function mutations and represents a useful new tool
      for dissecting the role that genes play in selected neurons.

PMID- 17459614
TI  - Conserved function of caspase-8 in apoptosis during bony fish evolution.
AB  - Caspase-8, a member of the caspase family, plays an important role in apoptotic
      signal transduction in mammals. Here we report the identification and
      characterization of the caspase-8 (casp8) gene in the zebrafish Danio rerio. The
      zebrafish casp8 gene has a genomic organization similar to mammalian casp8 genes,
      consisting of 10 exons. By chromosome mapping, we found that casp8 maps on
      linkage group 6 (LG6), a zebrafish chromosome segment orthologous to the long arm
      of human Chr. 2, which carries CASP8. In contrast, the zebrafish casp10-like gene
      and the cflar gene separately localize on LG9 and LG11, respectively, and these
      genes form a cluster with CASP8 on the human chromosome. This chromosomal
      segregation is unique to fish but not other vertebrates. Furthermore, we examined
      the function of zebrafish Casp8 protein in mammalian cells, and showed that it
      has pro-apoptotic activity when overexpressed. In addition, this molecule was
      capable of transmitting apoptotic signals mediated through not only Fas but also
      the TNF receptor in mouse Casp8-deficient cells. Expression analysis showed that
      casp8 is maternally expressed, and transcripts continue to be present throughout
      embryogenesis and into larval stages. These results show that zebrafish casp8 has
      a structure and function similar to mammalian CASP8 orthologs, and our study
      suggests that the role of caspase-8 in the apoptotic signal pathway has been
      conserved over at least 450 million years of vertebrate evolution.

PMID- 17459616
TI  - Extensive genetic recombination occurs in the field between different genotypes
      of Ehrlichia ruminantium.
AB  - The intracellular bacterium Ehrlichia ruminantium is the causative agent of
      heartwater throughout sub-Saharan Africa, Madagascar, and some islands of the
      Caribbean. The disease is tick-borne and causes substantial livestock losses,
      threatening food security and productivity in both the commercial and small-scale
      farming sectors in endemic areas. Immunization by infection and treatment is
      currently practised in South Africa, and it is known that a variety of
      immunotypes of the organism occur in the field, and that cross-protection between
      them varies widely from total to minimal. Future vaccines may therefore need to
      incorporate components from different genotypes so it is essential to have
      information on the extent of genetic variation among isolates. To obtain this
      information we amplified and sequenced a panel of eight core function genes from
      12 different cultured stocks originally isolated in different areas of Africa and
      the Caribbean. Phylogenetic trees inferred from the sequences yielded different
      branching orders for different genes, and the reason for this inconsistency
      appears to be that extensive recombination takes place between different
      genotypes in the field. It is possible that recombination occurs during the
      period when the organisms are extracellular within the tick, immediately after
      feeding and before intracellular infection is established, although detection of
      more than one genotype in DNA from single ticks is encountered infrequently. The
      results of the analysis show that the phylogenetic variation is greatest among
      the isolates of southern African origin, suggesting that this is the region where
      the parasite first evolved. It also appears likely that the Gardel genotype,
      isolated in the Caribbean, originally came from west central Africa, not from
      west Africa as had long been assumed.

PMID- 17459617
TI  - Newborn Individualized Developmental Care and Assessment Program (NIDCAP) -
      family-centered developmentally supportive care.
AB  - The theoretical framework behind family-centered, developmentally supportive care
      (NIDCAP) is endorsed by research from several scientific fields, including
      neuroscience, developmental and family psychology, medicine and nursing. However,
      the introduction of NIDCAP involves a considerable investment at all levels of
      the organization. NIDCAP requires some physical changes in the NICU as well as
      substantial educational efforts and changes in the practice of care. The findings
      of the presented NIDCAP studies have been encouraging, and NIDCAP has been very
      well received by nursing staff, neonatologists and parents. It also is attractive
      from an ethical point of view. It appears reasonable to recommend that nurseries
      implement NIDCAP and investigate developmentally supportive care in different
      cultural contexts and with diversified, randomized multicenter trials.

PMID- 17459619
TI  - A study of the uterine protein variations during the estrous cycle in the cow:
      molecular weights determination.
AB  - This study was carried out to investigate molecular weights (MW) of the uterine
      protein content as the first step in their identification, and their variations
      during the estrous cycle as a part of the uterine adjustments for provision of an
      appropriate environment for physiological events in the bovine. Of the 24 pro
      estrous, 21 estrous, 24 met-estrous and 46 diestrous uterine fluid samples
      prepared for our previous work, five samples in each phase were selected randomly
      and subjected to SDS-PAGE analysis in parallel with standard marker proteins to
      separate their protein content into fractions. By comparing these fractions with
      those of the standards, MWs of <14.4, 20, 30, 38, 40, 46, 67, 75, 85, 90, 160,
      200, 210, 270 and 330 kiloDaltons (kDa) were calculated, respectively. Proteins
      with MWs of less than 14.4kDa [5.3 mg/ml (7.5% of total protein)] were observed
      only in met-estrus. Proteins with the MW of 20 kDa [14.0 mg/ml (19.4%)] were
      found only in diestrus. Proteins with MW of 30 kDa in met-estrus [20.6 mg/ml
      (28.9%)] and diestrus [4.5 mg/ml (6.3%)], and 38 kDa proteins were observed in a
      considerable amount in pro-estrus [41.4 mg/ml (44.5%)] and estrus [40.0 mg/ml
      (44.2%)]. Forty kiloDaltons proteins were observed only in diestrus [5.5 mg/ml
      (7.6%)], and 46 kDa proteins were observed only in met-estrus [5.3mg/ml (7.6%)].
      Sixty seven, 75 and 330 kDa proteins were observed in all the phases of the cycle
      with different densities, the higher values recorded in diestrus, pro- and met
      estrus, respectively. Proteins with MW of 85 kDa were observed in all the phases
      but diestrus [9.8 mg/ml (10.5%), 8.6 mg/ml (9.5%) and 7.3 mg/ml (10.2%) for pro
      estrus, estrus and met-estrus, respectively], and proteins with MW of 90 kDa were
      observed in estrus [20.0mg/ml (22.1%)] and diestrus [3.3mg/ml (4.6%)]. Proteins
      of 160 kDa fraction were observed in pro-estrus [9.8 mg/ml (10.5%)] and met
      estrus [10.7 mg/ml (15%)], 200 kDa proteins were observed only in diestrus
      [6.3mg/ml (8.7%)]; finally, 210 and 270 kDa proteins were observed only in estrus
      [3.4 mg/ml (3.8%) and 2.0 mg/ml (2.2%), respectively]. It was concluded that
      protein profile of the bovine uterine lumen changes during the estrous cycle,
      both in quality and quantity, which may be a part of uterine adaptation for the
      physiological events. Further identification of these proteins would give us a
      better insight into their role in the bovine reproduction.

PMID- 17459620
TI  - Chitosan/cyclodextrin nanoparticles as macromolecular drug delivery system.
AB  - The aim of this study was to generate a new type of nanoparticles made of
      chitosan (CS) and carboxymethyl-beta-cyclodextrin (CM-beta-CD) and to evaluate
      their potential for the association and delivery of macromolecular drugs. CS and
      CM-beta-CD or mixtures of CM-beta-CD/tripolyphosphate (TPP) were processed to
      nanoparticles via the ionotropic gelation technique. The resulting nanoparticles
      were in the size range of 231-383 nm and showed a positive zeta potential ranging
      from +20.6 to +39.7 mV. These nanoparticles were stable in simulated intestinal
      fluid pH 6.8 at 37 degrees C for at least 4h. Elemental analysis studies revealed
      the actual integration of CM-beta-CD to CS nanoparticles. Insulin and heparin
      used as macromolecular model drugs, could be incorporated into the different
      nanocarriers with association efficiencies of 85.5-93.3 and 69.3-70.6%,
      respectively. The association of these compounds led to an increase of the size
      of the nanoparticles (366-613 nm), with no significant modification of their zeta
      potentials (+23.3 to +37.1 mV). The release profiles of the associated
      macromolecules were highly dependent on the type of molecule and its interaction
      with the nanomatrix: insulin was very fast released (84-97% insulin within 15
      min) whereas heparin remained highly associated to the nanoparticles for several
      hours (8.3-9.1% heparin within 8h). In summary, CS-CD (cyclodextrin)
      nanoparticles may be considered as nanocarriers for the fast or slow delivery of
      macromolecules.

PMID- 17459621
TI  - Mutagenic evaluation and chemical investigation of Byrsonima intermedia A. Juss.
      leaf extracts.
AB  - Byrsonima intermedia is a native species of the cerrado formation (tropical
      American savannah). In Brazil, this plant has been used for the treatment of
      fever, in ulcers, as a diuretic, as antiasthmatics and in skin infections.
      Members of the genus Byrsonima (Malpighiaceae) are employed not only in the folk
      medicine but also as food to make juice, jellies and liquor. The aim of this work
      was to evaluate the mutagenic effects of Byrsonima intermedia, common name
      'murici'. Phytochemical analysis of methanol extract furnished (+)-catechin, (-)
      epicatechin, quercetin-3-O-beta-d-galactopyranoside, methyl gallate, gallic acid,
      quercetin-3-O-alpha-l-arabinopyranoside, amentoflavone, quercetin, quercetin-3-O
      (2''-O-galloyl)-beta-galactopyranoside and quercetin-3-O-(2''-O-galloyl)-alpha
      arabinopyranoside. Methanol, hydromethanol and chloroform extracts were evaluated
      in mutagenic assay with Salmonella typhimurium (Ames test) and mice (Micronucleus
      test). The methanolic extract presented signs of mutagenic activity for the
      strains TA98 and TA100 in the Ames assay. Mutagenicity was not observed in vivo.

PMID- 17459622
TI  - Spirolactone iridoids might be responsible for the antileishmanial activity of a
      Peruvian traditional remedy made with Himatanthus sucuuba (Apocynaceae).
AB  - Extracts of seven medicinal plants used specifically against cutaneous
      leishmaniasis in the Madre de Dios region of Peru were evaluated in vitro against
      promastigote and axenic amastigote forms of Leishmania amazonensis. One of them
      showed interesting leishmanicidal activities (IC(50)=5 microg/ml in amastigotes).
      Bio-guided isolation of the stem bark's ethanol extract of Himatanthus sucuuba
      (Spruce ex Mull. Arg.) Woodson (Apocynaceae) afforded the spirolactone iridoids
      isoplumericin and plumericin. The latter showed a reduction of macrophage
      infection similar to that of the reference drug Amphotericin B (IC(50)=0.9 and 1
      microM, respectively). These findings validate the traditional use of Himatanthus
      sucuuba in the treatment of cutaneous leishmaniasis (Uta) in Peru.

PMID- 17459623
TI  - Traditional medicinal plants of cold desert Ladakh--used in treatment of cold,
      cough and fever.
AB  - This research paper presents the findings of an investigation on traditional
      remedies of cold, cough and fever among Boto (the Buddhists) tribal community of
      Leh-Ladakh region of India. Ladakh is one of the least populated regions of our
      country where major population lives in far-flung villages and higher elevations.
      Health care of tribal population is mainly dependent on traditional system of
      medicine which is popularly known as Amchi system of medicine. The Amchi system
      is principally based on Tibetan system of medicine. Fifty-six valuable species
      belonging to 21 families were identified with relevant information and documented
      in this paper with regard to their botanical name, family, collection number,
      local name, parts used and utilization by 'Amchis' (herbal practitioners) in
      treatment of cold, cough and fever.

PMID- 17459624
TI  - In vitro inhibition of proliferation of vascular smooth muscle cells by serum of
      rats treated with Dahuang Zhechong pill.
AB  - Dahuang Zhechong pill (DHZCP) is a famous and classical Chinese herbal
      prescription, which is clinically used to treat hepatic, gynecological and
      cardiovascular diseases in China. The aim of this study was to observe the
      effects of the serum of rats treated with DHZCP on the proliferation of cultured
      rat vascular smooth muscle cells (VSMCs) stimulated by platelet-derived growth
      factor (PDGF), oxidized low density lipoprotein (ox-LDL) and hyperlipidemic serum
      (HLS), and on DNA, protein and collagen syntheses of VSMCs induced by PDGF in
      vitro. VSMCs proliferation was assayed by measuring the cell viability with MTT
      method, and syntheses of DNA, protein and collagen were evaluated by detecting
      [(3)H]-thymidine, [(3)H]-leucine and [(3)H]-proline incorporations, respectively.
      The results showed that PDGF, ox-LDL and HLS stimulated the proliferation of rat
      VSMCs in vitro. The serum of rats treated with DHZCP significantly inhibited the
      proliferation of rat VSMCs induced by the above stimulants and the incorporations
      of [(3)H]-thymidine, [(3)H]-leucine and [(3)H]-proline into rat VSMCs induced by
      PDGF in comparison with the model control group (P<0.01). The data suggest that
      DHZCP is able to obviously inhibit VSMCs proliferation via interfering with
      syntheses of DNA and protein, and to decrease production of extracellular matrix
      by VSMCs through antagonizing collagen synthesis.

PMID- 17459625
TI  - Models for fingerprint pattern formation.
AB  - There is currently no general agreement on the process by which fingerprint
      (epidermal ridge) patterns form. Nevertheless, many possible mechanisms have been
      proposed. Based on an extensive literature review and mathematical modeling we
      argue that the pattern arises as the result of a buckling (folding) process in a
      cell layer of the epidermis. Using this model we were able to explain the long
      known observation that the pattern type is related to the geometry of the
      embryonal fingertip.

PMID- 17459626
TI  - The spectroscopic detection of exogenous material in fingerprints after
      development with powders and recovery with adhesive lifters.
AB  - The application of powders to fingerprints has long been established as an
      effective and reliable method for developing latent fingerprints. The powders
      adhere to the ridge pattern of the fingerprint only, thus allowing the image to
      be visualised. Fingerprints developed in situ at a crime scene routinely undergo
      lifting with specialist tapes to facilitate subsequent laboratory analysis. As
      with all recovered evidence these samples would be stored in evidence bags to
      allow secure transit from the scene to the laboratory and also to preserve the
      chain of evidence. In this paper, the application of Raman spectroscopy for the
      analysis of exogenous material in latent fingerprints is reported for
      contaminated fingerprints that had been treated with powders and also
      subsequently lifted with adhesive tapes. A selection of over the counter (OTC)
      analgesics were used as samples for the analysis and contaminated fingerprints
      were deposited on clean glass slides. The application of aluminium or iron based
      powders to contaminated fingerprints did not interfere with the Raman spectra
      obtained for the contaminants. In most cases background fluorescence attributed
      to the sebaceous content of the latent fingerprint was reduced by the application
      of the powder thus reducing spectral interference. Contaminated fingerprints
      developed with powders and then lifted with lifting tapes were also examined. The
      combination of these two techniques did not interfere with the successful
      analysis of exogenous contaminants by Raman spectroscopy. The lifting process was
      repeated using hinge lifters. As the hinge lifters exhibited strong Raman bands
      the spectroscopic analysis was more complex and an increase in the number of
      exposures to the detector allowed for improved clarification. Raman spectra of
      developed and lifted fingerprints recorded through evidence bags were obtained
      and it was found that the detection process was not compromised in any way.
      Although the application of powders did not interfere with the detection process
      the time taken to locate the contaminant was increased due to the physical
      presence of more material within the fingerprint. The presence of interfering
      Raman bands from lifting tapes is another potential complication. This, however,
      could be removed by spectral subtraction or by the choice of lifting tapes that
      have only weak Raman bands.

PMID- 17459627
TI  - Third molar development according to chronological age in populations from
      Spanish and Magrebian origin.
AB  - Spain is frequently the entrance country into the European Union for undocumented
      immigrants, especially those from the Magreb (Northern Africa). Forensic age
      estimates for these persons are difficult because systematic studies of dental
      maturity are lacking. Three different populations were analyzed to determine the
      pattern of development of third molars as a tool for age estimation in people of
      different ethnic and geographic origin. Orthopantomograms from two different
      populations of Spanish origin (Galicia in northwestern continental Spain, and
      Ceuta, a Spanish province in Northern Africa) were compared to radiographs of
      molars from a Magrebian population (Northern Africa) resident in Ceuta.
      Orthopantomograms were obtained from a private dental clinic (n=344) in Galicia
      and from the Public Oral Health Services (n=228) in Ceuta. We looked for
      differences in third molar mineralization (determined with the Demirjian scale)
      that might serve as age indicators (older versus younger than 18 years).
      Differences in maturation patterns were found between sexes and populations of
      origin. Mineralization of tooth 38 was more advanced in males than females among
      subjects 18 years of age and older in all three populations. Moreover,
      mineralization of tooth 38 in subjects aged 18 years and older was significantly
      slower in the Spanish-Galicia population than in the Magrebian-Ceuta population.
      We found no significant differences between Magrebian and Spanish individuals
      from Ceuta. We conclude that differences in tooth 38 mineralization may be
      related more with socio-geographical than ethnic origin (ancestry), and thus
      constitute evidence of the relevance of socio-geographic rather than genetic
      factors in third molar development. We used ROC analysis to determine the
      accuracy of the examiner's ability to correctly estimate age as younger or older
      than 18 years. The results suggest that Demirjian stage for tooth 38 can be
      considered a good indicator of age in all three populations.

PMID- 17459628
TI  - Isolating cells from non-sperm cellular mixtures using the PALM microlaser micro
      dissection system.
AB  - Use of the Positioning Ablation Laser MicroBeam (PALM) microlaser system to
      isolate specific cellular components from somatic cellular mixtures (blood and
      saliva) prior to DNA extraction and typing is compared with routine DNA
      extraction and typing of the same mixture samples. Mixtures of blood and saliva
      at differing ratios generated complex DNA profiles that included allele peaks
      originating from each of the donors, or just those of the major contributor.
      Isolation of cells with the PALM microlaser prior to DNA extraction allowed
      informative, single-source, DNA profiles to be generated from a known cell
      type/origin.

PMID- 17459629
TI  - Oncocytic carcinoma of the nasal cavity with widespread lymph node metastases.
AB  - The first case of oncocytic carcinoma which arose from the inferior turbinate of
      the nasal cavity with orbital invasion through the nasolacrimal canal and
      widespread lymph node metastases in the neck and face is reported here. The tumor
      metastasized rapidly, spread widely to the whole neck and face, and produced
      tumor emboli in the lymphatics and extranodal extension by rupture of the lymph
      node capsule in the absence of clinically palpable regional lymph node
      enlargement. We think the oncocytic carcinoma of the nasal cavity may be a high
      grade malignancy tumor.

PMID- 17459630
TI  - [Users sceptical about generic drugs: an anthropological approach].
AB  - BACKGROUND: Since the enactment of the 2002 legislative measures favoring the
      prescription of generic drugs, various quantitative studies have shown that
      approval by prescribers and users has risen in France. Nevertheless, scepticism
      remains as well as distrust towards these drugs focusing on their effectiveness
      compared with brand-name drugs, on potential dangers, and on the interruption
      they cause in prescription and consumption habits. Using a comprehensive
      approach, this article analyzes the social and cultural logic behind the negative
      image of generic drugs. METHODS: The materials issued from an ethnographic study
      on the prescription of drugs for high blood pressure. Sixty-eight interviews were
      undertaken between April 2002 and October 2004 with people (39 women and 29 men,
      between the age of 40 and 95, 52 over the age of 60) treated for over a year for
      high blood pressure in rural areas in the Southeast of France. Thirteen people
      provided unsolicited opinions about generic drugs. RESULTS: Analysis of the
      information collected shows that users have various representations of generic
      drugs, including the idea of counterfeited and foreign drugs. These
      representations interfere with the adjustment process and the development of
      consumer loyalty. They are part of a set of social representations about drugs
      which form and express the user's reality. In these representations, the drug is
      an ambivalent object, carrier of both biological effectiveness and toxicity; it
      is also the metonymical extension of the prescriber, bestowing upon the
      prescription a symbolic value. CONCLUSION: By placing the generic drug in its
      network of symbolic and social meaning, this study highlights the coherence of
      the scepticism towards generic drugs by consumers (and prescribers) with a system
      of common opinion in which drugs are everyday things, personalized and compatible
      with users, symbolic exchange carriers in the physician-patient relationship, and
      in which confidence in the drug is also that given to the health care system in
      general.

PMID- 17459631
TI  - [Underweight prevention and treatment of the young child in Mono (Benin)].
AB  - BACKGROUND: This study aimed to assess the prevention and treatment effectiveness
      of underweight in less than two years old children admitted in 2001 to community
      nutrition programme of Mono area in Benin. METHODS: A longitudinal retrospective
      survey took place in 30 villages chosen at random. It concerned a sample of 1799
      children. Inside of those children, during the 2001 year, when they were admitted
      to the programme, 1545 were without underweight, have had more than one month
      following visit and about them the underweight effectiveness prevention had been
      analyzed; the others 111 were underweighted, have had more than one month
      following visit and about them the underweight treatment had been assessed. The
      143 other children have been followed for only one month. The prevention
      effectiveness had been explored by the evolution of the cumulative incidence of
      underweight according to the number of following visit and the underweight
      incidence density. The treatment effectiveness has been analysed by calculating
      the recovery rate and incidence density. RESULTS: During 2001, there have been
      observed 10% for the underweight cumulative incidence and 51.4% for the
      cumulative incidence of underweight recovery. The underweight and recovery
      incidence density were respectively 14 cases for 1000 persons-months of following
      and 118 cases for 1000 persons-months of following. The children with serious
      underweight at their last following visit have had the number of following visits
      lower than those who were with moderate underweight. The recovery was arrived
      after two to twelve months. There was a significant increase of underweight
      prevalence with the increase of following visit number inside the children with a
      normal weight at their admission into the programme. CONCLUSION: During the 2001
      following, the underweight prevention and treatment activities of community
      nutrition workers have been little effectiveness. The low level of instruction of
      community nutrition workers, their low level of knowledge of essential community
      nutrition activities, their multiple tasks and the not used appropriate foods for
      the treatment of underweight are the possible causes of the poor performance
      observed.

PMID- 17459632
TI  - [Epidemiology of tuberculosis in France in 2005].
AB  - This article presents results on cases of tuberculosis disease notified in France
      in 2005 by mandatory notification. In 2005, a total of 5,374 cases were notified
      in France, representing a rate of 8.9 cases per 100,000. The notification rate
      per 100,000 was below 10 in all French regions, except the Ile-de-France and
      French Guyana (with respective rates of 19.7/10(5) and 44.0/10(5)). Notification
      rates were higher in some population groups such as people born abroad
      (41.5/10(5)), especially those born in sub-Saharan Africa (160/10(5)), and those
      recently (<2 years) arrived in France (251/10(5)), in homeless people
      (214/10(5)), and in persons aged 80 years and over (21.7/10(5)). Pulmonary
      tuberculosis accounted for 73% of notified cases, 79% of which were contagious
      (positive direct examination of sputum, positive culture). Results from the
      notification of tuberculosis disease in 2005 indicate a continuing decrease of
      incidence in France. However, the high incidence in some population groups
      requires adapting public health actions to the needs of population groups more
      exposed to tuberculosis.

PMID- 17459633
TI  - In vitro activity of ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and
      gatifloxacin against multidrug-resistant Mycobacterium tuberculosis in Rio de
      Janeiro Brazil.

PMID- 17459634
TI  - [Emergence of multidrug resistant Salmonella strains in Lome (Togo)].
AB  - OBJECTIVE: This study had for aim to compare antibiotic resistance of 332
      Salmonella enterica strains identified in human samples in the course of
      infections, in Lome. DESIGN: The strains were collected over two periods: 1998
      2002 (N=168) and 2003-2004 (N=164). The antibiotic susceptibility test was
      performed by disk diffusion assay. RESULTS: The main serotypes identified were
      147 Salmonella Typhi (44.3%), 97 Salmonella Typhimurium (29.2%), and 74
      Salmonella Enteritidis (22.3%). The proportions of strains resistant to
      chloramphenicol, cotrimoxazol, and amoxicillin (first line antibiotics) varied
      respectively from 33, 46, and 57% in 1998-2002 to 73, 79, and 82% in 2003-2004
      (P<0.0001). The percentage of resistance to ciprofloxacin or ceftriaxone was
      inferior to 10%. CONCLUSION: Fluoroquinolones and third generation cephalosporins
      have become the first line antibiotics for the treatment of Salmonella in Lome
      (Togo).

PMID- 17459635
TI  - [Antimicrobial susceptibility of Streptococcus agalactiae strains in Monastir].
AB  - OBJECTIVE: The aim of this study was to determine the antimicrobial
      susceptibility of Streptococcus agalactiae strains in Monastir (Tunisia). METHOD:
      This retrospective study included 300 strains of S. agalactiae from several
      pathological samples collected at the Monastir Fattouma Borguiba Hospital. The
      identification was based on conventional bacteriological features. Serogrouping
      was performed using agglutination tests. The susceptibility to antibiotics was
      studied according to the Antibiogram Committee of the French Society of
      Microbiology recommendations. RESULTS: S. agalactiae was mainly isolated from
      patients with vaginal infections (31.3%) and urinary tract infections (24.7%).
      All strains were susceptible to penicillin G. Resistance was mostly observed to
      erythromycin (38.5%) and lincomycin (36.6%). 6.5% were highly resistant to
      kanamycin and 0.6% to gentamicin. CONCLUSION: Penicillin remains the most
      effective antibiotic, but resistance to other antibiotics is emerging. This
      justifies the routine studying of antimicrobial susceptibility in S. agalactiae
      stains.

PMID- 17459636
TI  - [Simultaneous outbreaks of rotavirus and respiratory syncytial virus in Paris: a
      12-year survey].
AB  - OBJECTIVE: The authors had for aim to study the coincidence of RSV and rotavirus
      epidemic peaks in pediatric patients hospitalized in the Paris area. METHODOLOGY:
      A retrospective hospital-based monocentric cohort study was made over a 12-year
      period (1993-2004). Clinical and laboratory findings were prospectively collected
      on admission. RESULTS: Three thousand and four hundred ninety-six stool samples
      were positive for rotavirus; 3,507 nasopharyngeal aspirates were positive for
      RSV. The coincidence of epidemic peaks for both viruses in November, December,
      and January was observed during the 12 years of the study. CONCLUSION: The exact
      coincidence of winter outbreaks of RSV and rotavirus is a characteristic of the
      Paris area. It contributes to increase overcrowding in pediatric units and
      nosocomial infections.

PMID- 17459637
TI  - [Two cases of spondylodiscitis due to Candida sp].
AB  - In recent years, the incidence of systemic infections due to Candida increased,
      but the incidence of spondylodiscitis remained low, and epidural involvement
      during such infection was seldom reported. The purpose of this study was to
      report the cases of 2 young male heroin addicts who developed spondylodiscitis
      due to Candida sp., with epidural involvement. In one case, a microbiological
      diagnosis was obtained after biopsy. In the other case, the diagnosis was based
      on serological data and Candida antigenemia. In both cases, an oral fluconazole
      based therapy was administered at first (because of a poor peripheral venous
      system), but proved to be inefficient. A secondary therapy by liposomal
      amphotericin B proved efficient allowing a favourable evolution. This pathology
      raised a number of problems concerning diagnosis and treatment. The clinical data
      was non-specific the paraclinical diagnosis required MRI, and biopsy. When
      microbiological assessment is negative, serology and the antigenemia can be
      useful. The treatment pattern suggested for the management of bone and joint
      infections is: intravenous amphotericine B for 2-3 weeks, followed by oral
      administration of fluconazole or voriconazole for 6-12 month. Surgical treatment
      is recommended only to patients ay risk of neurological disorders or severe
      epidural abscess.

PMID- 17459638
TI  - The role of imaging in Graves' disease: a cost-effectiveness analysis.
AB  - According to many guidelines, scintigraphy remains the first suggested diagnostic
      procedure in hyperthyroid patients in spite of the widespread availability of
      ultrasounds. The aim of this study was to evaluate the cost-effectiveness of
      sonography versus scintigraphy in the management of Graves's disease, and to
      assess ultrasound features suggesting cancer in detecting thyroid nodules. Among
      1470 hyperthyroid patients evaluated in our department from 2002 to 2005, 426
      (29%) had Graves' disease: echographic and scintigraphic features were not
      suggestive of GD in 20/426 (4.8%) and 11/426 (2.6%) patients, respectively
      (p=0.763), even if one of the two procedures was almost always diagnostic.
      Ultrasound identified 68/426 (16%) patients with a concomitant solid lesion,
      while scintigraphy detected only 9/426 (2.1%) "cold" nodules (p<0.001). Thyroid
      cancer was diagnosed in 30/68 (47.7%) patients. Malignancy presented at
      ultrasound investigation blurred margins (26.7% versus 15.8%),
      microcalcifications (33.3% versus 28.9%) and an anteroposterior and transverse
      diameter ratio>or=1 (73.3% versus 71.1%); more frequently than benign nodules,
      but this was not statistically significant. The total cost to obtain a diagnosis
      by ultrasound was euro14645.34 (euro13312.5 for echography+euro1332.84 for
      scintigraphy in the 29 patients "negative" at echographic evaluation for GD)
      versus euro19922.71 by scintigraphy (euro19578.96 for scan+euro343.75 for
      ultrasounds in the 11 patients "negative" at scintigraphy). Our data show no
      difference in terms of diagnosis between sonography and scintigraphy. Indeed,
      scintigraphy was less sensitive in detecting nodules (often of malignant nature)
      than ultrasound, and, moreover, with a consequent increase of the direct cost of
      nodule management when scintigraphy is the first line procedure. In conclusion,
      according to our results, we suggest that ultrasounds with color-Doppler
      evaluation should be performed as first step in all hyperthyroid patients, and
      that scintigraphic examination should be limited only to the uncommon cases,
      where physician's observation, laboratory assays and/or ultrasounds are not
      diagnostic.

PMID- 17459639
TI  - Dense mode clustering in brain maps.
AB  - A mode-based clustering method is developed for identifying spatially dense
      clusters in brain maps. This type of clustering focuses on identifying clusters
      in brain maps independent of their shape or overall variance. This can be useful
      for both localization in terms of interpretation and for subsequent graphical
      analysis that might require more coherent or dense regions of interest as
      starting points. The method automatically does signal/noise sharpening through
      density mode seeking. We also discuss the problem of parameter selection with
      this method and propose a new method involving 2-parameter control surface, in
      which we show that the same cluster solution results from tradeoff of these 2
      parameters (the local density k and the radius r of the spherical kernel). We
      benchmark the new dense mode clustering by using several artificially created
      data sets and brain imaging data sets from an event perception task by perturbing
      the data set with noise and measuring three kinds of deviation from the original
      cluster solution. We present benchmark results that demonstrate that the mode
      clustering method consistently outperforms the commonly used single-linkage
      clustering, k means method (centroid method) and Ward's method (variance method).

PMID- 17459640
TI  - T2* measurements in human brain at 1.5, 3 and 7 T.
AB  - Measurements have been carried out in six subjects at magnetic fields of 1.5, 3
      and 7 T, with the aim of characterizing the variation of T2* with field strength
      in human brain. Accurate measurement of T2* in the presence of macroscopic
      magnetic field inhomogeneity is problematic due to signal decay resulting from
      through-slice dephasing. The approach employed here allowed the signal decay due
      to through-slice dephasing to be characterized and removed from data, thus
      facilitating an accurate measurement of T2* even at ultrahigh field. Using double
      inversion recovery turbo spin-echo images for tissue classification, an analysis
      of T2* relaxation times in cortical grey matter and white matter was carried out,
      along with an evaluation of the variation of T2* with field strength in the
      caudate nucleus and putamen. The results show an approximately linear increase in
      relaxation rate R2* with field strength for all tissues, leading to a greater
      range of relaxation times across tissue types at 7 T that can be exploited in
      high-resolution T2*-weighted imaging.

PMID- 17459641
TI  - Study on the interaction between salicylic acid and catalase by spectroscopic
      methods.
AB  - The interaction between catalase (CAT) and salicylic acid (SA) was studied by
      fluorescence and UV-vis spectroscopic techniques. The quenching mechanism of
      fluorescence of BSA by CAT was discussed to be a static quenching procedure. The
      number of binding sites n and apparent binding constant K was measured by
      fluorescence quenching method. The thermodynamics parameter DeltaH, DeltaG,
      DeltaS were calculated. The results indicate the binding reaction was both
      entropy-driven and the enthalpy-driven, and the hydrogen bond and van der Waals
      force played major role in the binding reaction. The binding sites of SA with CAT
      was investigated to be approached the microenvironment of Trp by the synchronous
      fluorescence spectrometry. The distance r between donor (CAT) and acceptor (SA)
      was obtained according to Forster theory of non-radioactive energy transfer.

PMID- 17459642
TI  - Sensitive determination of ketoprofen using flow injection with chemiluminescence
      detection.
AB  - A rapid chemiluminescence method is described for the determination of ketoprofen
      by combining the flow injection technique and its sensitizing effect on the weak
      chemiluminescence reaction between sulfite and acidic permanganate. The optimum
      conditions for the chemiluminescence emission were intensity. A mechanism for the
      chemiluminescence reaction has been proposed on the basis of chemiluminescent
      spectra. Ketoprofen can be determined over the concentration range of 5.0x10(-8)
      to 3.0x10(-6) mol/L with a correlation coefficient of 0.9999 and a detection
      limit of 2.0x10(-8) mol/L (3sigma). The relative standard deviation (R.S.D.) for
      15 repetitive determinations of 1.0x10(-6) mol/L ketoprofen is 0.8%. The utility
      of this method was demonstrated by determining ketoprofen in capsules and human
      urine sample.

PMID- 17459643
TI  - Qualitative and quantitative analyses of nucleosides and nucleobases in Ganoderma
      spp. by HPLC-DAD-MS.
AB  - A high-performance liquid chromatography-diode array detector-mass spectrometry
      (HPLC-DAD-MS) analytical method was developed for detection of the nucleosides
      and nucleobases in two species of Lingzhi, the dried sporophore of Ganoderma
      lucidum and G. sinense. The method, combining advantages of both DAD and MS, was
      successfully used to qualitatively identify for six nucleosides namely,
      adenosine, cytidine, guanosine, inosine, thymidine, uridine and five nucleobases
      namely, adenine, guanine, hypoxanthine, thymine and uracil in Lingzhi samples.
      Quantitative analyses showed that uridine was the most abundant nucleoside in
      these Lingzhi samples and the contents of nine target analytes were found to be
      different in pileus and stipes of the fruiting bodies and among the different
      species of G. spp. The established method might apply as an alternative approach
      for the quality assessment of Lingzhi.

PMID- 17459644
TI  - Porcine follicular fluids: comparison of solid-phase extraction and matrix solid
      phase dispersion for the GC-MS determination of hormones during follicular
      growth.
AB  - The capabilities of solid-phase extraction (SPE) and matrix solid-phase
      dispersion (MSPD) for the determination of the hormones 17beta-estradiol, 2
      hydroxyestradiol, 4-hydroxyestradiol and 2-methoxyestradiol by gas chromatography
      mass spectrometry (GC-MS) in a very complex matrix like porcine follicular fluids
      were compared, thus proving the highest effectiveness of the SPE technique.
      Validation was carried out in terms of limit of quantitation (LOQ), precision,
      accuracy, recovery and stability. LOQ values in the low microg kg(-1) were
      achieved, with all the other parameters satisfying the acceptance criteria for
      the validation of bioanalytical methods. The applicability of the method to the
      determination of the hormones in porcine follicular fluids was demonstrated, thus
      allowing to observe an increase of the concentration of the hormones during the
      follicular growth.

PMID- 17459645
TI  - High-performance liquid chromatographic determination and pharmacokinetic study
      of vitexin-2''-O-rhamnoside in rat plasma after intravenous administration.
AB  - A simple and specific high-performance liquid chromatographic (HPLC) method was
      developed for the pharmacokinetic study of vitexin-2''-O-rhamnoside (VOR) in rat
      after intravenous administration. The plasma samples were deproteinized with
      methanol after addition of internal standard (i.s.) hesperidin. HPLC analysis was
      performed on a Diamonsil ODS C18 analytical column, using acetonitrile-0.3%
      formic acid (20:80, v/v) as the mobile phase with UV detection at 270 nm. The
      standard curve was linear over the range of 0.1070-21.41 microg/mL in rat plasma.
      The average extraction recovery of VOR was 97.9+/-3.1%, and the relative standard
      deviations (R.S.D.s) of the intra- and inter-day precisions were no more than 7.4
      and 8.5%, respectively. The lower limit of quantification (LLOQ) was 0.1070
      microg/mL. The AUC of VOR was proportional to the dose after intravenous
      administration of 15, 30, 60 and 120 mg/kg body weight, and the elimination half
      life (t1/2beta), systemic clearance (Cl) and apparent volume of distribution (Vc)
      were not significantly different among the four doses, and all the results
      indicated that the pharmacokinetics of VOR in rat obeyed first-order kinetics.

PMID- 17459646
TI  - The use of the Xenopus oocyte as a model system to analyze the expression and
      function of eukaryotic heat shock proteins.
AB  - The analysis of the expression and function of heat shock protein (hsp) genes, a
      class of molecular chaperones, has been greatly aided by studies carried out with
      Xenopus oocytes. The large size of the oocyte facilitates microinjection of DNA,
      mRNA or protein, permits manual dissection of nuclei, and allows certain assays
      to be performed with single oocytes. These and other characteristics were useful
      in identifying the cis- and trans-acting factors involved in hsp gene
      transcription as well as the role of chaperones and co-chaperones in the
      repression and activation of heat shock factor. Xenopus oocytes were used to
      examine heat shock protein (HSP) molecular chaperone function as well as their
      involvement in intracellular trafficking, maturation, and secretion of protein.
      Possible new areas of research with this system include the role of membranes in
      the heat shock response, involvement of HSPs in viral replication and maturation,
      and in vivo NMR spectroscopy of microinjected HSPs.

PMID- 17459647
TI  - Cofactor regeneration for sustainable enzymatic biosynthesis.
AB  - Oxidoreductases are attractive catalysts for biosynthesis of chiral compounds and
      polymers, construction of biosensors, and degradation of environmental
      pollutants. Their practical applications, however, can be quite challenging since
      they often require cofactors such as nicotinamide adenine dinucleotide (NAD) and
      nicotinamide adenine dinucleotide phosphate (NADP). These cofactors are generally
      expensive. Efficient regeneration of cofactors is therefore critical to the
      economic viability of industrial-scale biotransformations using oxidoreductases.
      The chemistry of cofactor regeneration is well known nowadays. The challenge is
      mostly regarding how to achieve the regeneration with immobilized enzyme systems
      which are preferred for industrial processes to facilitate the recovery and
      continuous use of the catalysts. This has become a great hurdle for the
      industrialization of many promising enzymatic processes, and as a result, most of
      the biotransformations involving cofactors have been traditionally performed with
      living cells in industry. Accompanying the rapidly growing interest in industrial
      biotechnology, immobilized enzyme biocatalyst systems with cofactor regeneration
      have been the focus for many studies reported since the late 1990s. The current
      paper reviews the methods of cofactor retention for development of sustainable
      and regenerative biocatalysts as revealed in these recent studies, with the
      intent to complement other reviewing articles that are mostly regeneration
      chemistry-oriented. We classify in this paper the methods of sustainable cofactor
      regeneration into two categories, namely membrane entrapment and solid-attachment
      of cofactors.

PMID- 17459649
TI  - Oxidative stress modulates membrane bound ATPases in brain regions of PCB
      (Aroclor 1254) exposed rats: protective role of alpha-tocopherol.
AB  - Polychlorinated biphenyls (PCBs) are a class of widely dispersed and
      environmentally persistent organic compounds. PCBs exhibit a wide range of
      toxicological effects including neurotoxicity. Vitamin E (alpha-tocopherol) is an
      important lipid soluble antioxidant placed in a special region of membranes.
      Large amounts of energy are required to maintain the signaling activities of the
      cells in the central nervous system (CNS). Membrane proteins that control ion
      gradients across organellar and plasma membranes appear to be particularly
      susceptible to oxidation-induced changes. The aim of this study was to determine
      the protective role of vitamin E on Aroclor 1254 induced modulation in membrane
      bound ATPases in brain regions of rats. One group of rats received corn oil as
      vehicle for 30days as control. The other group of rats were administered Aroclor
      1254 at a dose of 2mgkg(-1) bwday(-1) intraperitoneally for 30days. One group of
      rats received vitamin E (50mgkg(-1) bwday(-1)) orally simultaneously with Aroclor
      1254 for 30days. After 30days, the animals were euthanized and the brain was
      dissected to hypothalamus and hippocampus to determine the following parameters.
      Hydrogen peroxide (H2O2), Lipid peroxidation (LPO) and the activities of Na+K+
      ATPase, Ca2+-ATPase and Mg2+-ATPase were determined. Reduced glutathione (GSH)
      level was also determined. Activities of all the enzymes were decreased while an
      increase in H2O2 and LPO were observed in selected brain regions of PCB treated
      animals. Simultaneous vitamin E treatment in PCB exposed animals restored all the
      parameters significantly. These results suggest that oxidative stress is involved
      in the inhibitory effect of PCB (Aroclor 1254) on membrane bound ATPases in
      selected brain regions. alpha-tocopherol acts against PCB induced neurotoxicity
      by decreasing oxidative stress.

PMID- 17459648
TI  - Insulin-like growth factor-I (IGF-I) inhibits neuronal apoptosis in the
      developing cerebral cortex in vivo.
AB  - Increased expression of insulin-like growth factor-I (IGF-I) in embryonic neural
      progenitors in vivo has been shown to accelerate neuron proliferation in the
      neocortex. In the present study, the in vivo actions of (IGF-I) on naturally
      occurring neuron death in the cerebral cortex were investigated during embryonic
      and early postnatal development in a line of transgenic (Tg) mice that
      overexpress IGF-I in the brain, directed by nestin genomic regulatory elements,
      beginning at least as early as embryonic day (E) 13. The areal density of
      apoptotic cells (N(A), cells/mm2) at E16 in the telencephalic wall of Tg and
      littermate control embryos was determined by immunostaining with an antibody
      specific for activated caspase-3. Stereological analyses were conducted to
      measure the numerical density (N(V), cells/mm3) and total number of
      immunoreactive apoptotic cells in the cerebral cortex of nestin/IGF-I Tg and
      control mice at postnatal days (P) 0 and 5. The volume of cerebral cortex and
      both the N(V) and total number of all cortical neurons also were determined in
      both cerebral hemispheres at P0, P5 and P270. Apoptotic cells were rare in the
      embryonic telencephalic wall at E16. However, the overall N(A) of apoptotic cells
      was found to be significantly less by 46% in Tg embryos. The volume of the
      cerebral cortex was significantly greater in Tg mice at P0 (30%), P5 (13%) and
      P270 (26%). The total number of cortical neurons in Tg mice was significantly
      increased at P0 (29%), P5 (29%) and P270 (31%), although the N(V) of cortical
      neurons did not differ significantly between Tg and control mice at any age.
      Transgenic mice at P0 and P5 exhibited significant decreases in the N(V) of
      apoptotic cells in the cerebral cortex (31% and 39%, respectively). The vast
      majority of these apoptotic cells (> 90%) were judged to be neurons by their
      morphological appearance. Increased expression of IGF-I inhibits naturally
      occurring (i.e. apoptotic) neuron death during early postnatal development of the
      cerebral cortex to a degree that sustains a persistent increase in total neuron
      number even in the adult animal.

PMID- 17459650
TI  - Vesicular stomatitis virus infection triggers apoptosis associated with decreased
      DeltaNp63alpha and increased Bax levels in the immortalized HaCaT keratinocyte
      cell line.
AB  - In view of the powerful inherent oncolytic activity exhibited by the vesicular
      stomatitis virus (VSV) in several tumor types, we set out to investigate the
      susceptibility of the immortalized HaCaT keratinocyte cell line to VSV, and
      analyzed the role of apoptosis in the VSV-mediated induction of cell death.
      Indirect immunofluorescence assays, Western blot analyses and plaque titrations
      demonstrated that the HaCaT cell line was permissive to VSV replication. The
      results of ELISA for detection of the enrichment of nucleosomes in the cytoplasm
      of apoptotic cells revealed that VSV infection elicits the apoptotic death of
      HaCaT cells. Mock-infected HaCaT cells displayed the endogenous expression of
      DeltaNp63alpha, p53 mutated on UV hot spots (p53(mt)), Bcl-2 and p21 Bax. The
      levels of DeltaNp63alpha and p53(mt) were decreased, Bcl-2 remained unaffected,
      while the expressions of p21Bax and p18 Bax were increased in VSV-infected HaCaT
      cells. Together, these data demonstrate that VSV replicates efficiently and
      triggers apoptosis in the immortalized HaCaT keratinocyte cell line. The VSV
      mediated alterations in the expressions of DeltaNp63alpha and Bax may be
      implicated in the apoptotic responses of infected cells and may also sensitize to
      other apoptotic stimuli. These findings may stimulate further studies with the
      goal of developing VSV-based virotherapy into an effective modality for the
      treatment of epithelial-derived malignant tumors of the skin.

PMID- 17459651
TI  - Antileishmanial 2-substituted quinolines: in vitro behaviour towards biological
      components.
AB  - Quinolines substituted on their carbon 2 have in vivo antileishmanial activity
      but some of them could not be detected in plasma when assayed for pharmacokinetic
      studies, suggesting a sequestration of the drugs by components of the blood
      compartment. The present study, performed on three quinolines (1, 2 and 3),
      showed strong affinity for two of them (2 and 3) with red blood cells (RBCs),
      whereas quinoline 1 did not react with them. This process was saturable,
      temperature dependant and positively correlated with the in vitro antileishmanial
      activity of the quinolines. In addition, a rapid and spontaneous reaction with
      thiol groups was demonstrated for unsaturated quinolines 2 and 3. The reactivity
      with RBCs could be part of the compounds targeting to the parasite. These results
      illustrate that derivatives of the quinoline series with similar antileishmanial
      in vivo activity have different behaviour in the blood compartment.

PMID- 17459652
TI  - Effect of pulsed electromagnetic field stimulation on knee cartilage, subchondral
      and epyphiseal trabecular bone of aged Dunkin Hartley guinea pigs.
AB  - It has been demonstrated that pulsed electromagnetic field (PEMF) stimulation has
      a chondroprotective effect on osteoarthritis (OA) progression in the knee joints
      of the 12-month-old guinea pigs. The aim of the present study was to discover
      whether the therapeutic efficacy of PEMFs was maintained in older animals also in
      more severe OA lesions. PEMFs were administered daily (6 h/day for 6 months) to
      15-month-old guinea pigs. The knee joints (medial and lateral tibial plateaus,
      medial and lateral femoral condyles) were evaluated by means of a
      histological/histochemical Mankin modified by Carlsson grading score and
      histomorphometric measurements of cartilage thickness (CT), fibrillation index
      (FI), subchondral bone thickness (SBT) and epiphyseal bone microarchitecture
      (bone volume: BV/TV; trabecular thickness: Tb.Th; trabecular number: Tb.N;
      trabecular separation: Tb.SP). Periarticular knee bone was also evaluated with
      dual X-ray absorptiometry (DXA). PEMF stimulation significantly changed the
      progression of OA lesions in all examined knee areas. In the most affected area
      of the knee joint (medial tibial plateau), significant lower histochemical score
      (p<0.0005), FI (p<0.005), SBT (p<0.05), BV/TV (p<0.0005), Tb.Th (p<0.05) and Tb.N
      (p<0.05) were observed while CT (p<0.05) and Tb.Sp (p<0.0005) were significantly
      higher than in SHAM-treated animals. DXA confirmed the significantly higher bone
      density in SHAM-treated animals. Even in the presence of severe OA lesions PEMFs
      maintained a significant efficacy in reducing lesion progression.

PMID- 17459653
TI  - [Obesity, immune resistance and metabolic complications: what morbid obesity can
      teach the doctor].
AB  - Abdominal -- and not peripheral -- obesity induces insulin resistance. Morbid
      obesity is not always accompanied by either diabetes mellitus or metabolic
      syndrome. Development of morbid obesity can require appropriate insulin secretion
      and recruitment of small insulin-sensitive adipocytes, able to store fatty acids.
      These fatty acids are therefore not stored in ectopic sites (muscle, liver,
      islets of Langerhans), and neither insulin resistance nor glucolipid toxicity
      develops and causes insulin deficiency. This explains the relative rarity of
      diabetes in morbid obesity. Patients with morbid obesity are at greater risk of
      developing mechanical complications (e.g. cardiac, pulmonary, or locomotor
      system, or sleep apnea) than metabolic complications or cardiovascular heart
      disease.

PMID- 17459655
TI  - Transcriptional stimulation of anthrax toxin receptors by anthrax edema toxin and
      Bacillus anthracis Sterne spore.
AB  - We used quantitative real-time RT-PCR to not only investigate the mRNA levels of
      anthrax toxin receptor 1 (ANTXR1) and 2 (ANTXR2) in the murine J774A.1 macrophage
      cells and different tissues of mice, but also evaluate the effect of anthrax
      edema toxin and Bacillus anthracis Sterne spores on the expression of mRNA of
      these receptors. The mRNA transcripts of both receptors were detected in J774A.1
      cells and mouse tissues such as the lung, heart, kidney, spleen, stomach,
      jejunum, brain, skeleton muscle, and skin. The ANTXR2 mRNA level was
      significantly higher than that of ANTXR1 in J774A.1 cells and all tissues
      examined. The mRNA expression of both receptors in the lung was the highest among
      the tissues evaluated. Interestingly, the mRNA expression of both receptors in
      J774A.1 cells was upregulated by edema toxin. In addition, ANTXR mRNA expression
      in the lung was downregulated after subcutaneous inoculation of B. anthracis
      Sterne spores as well as after intranasal administration of anthrax toxin-based
      vaccine BioThrax. These results suggest that anthrax edema toxin and B. anthracis
      Sterne spore are involved in the ANTXR mRNA regulation in host cells.

PMID- 17459656
TI  - Detection of xenobiotic-induced DNA damage by the comet assay applied to human
      and rat precision-cut liver slices.
AB  - The comet assay is a simple and sensitive method for measuring DNA damage at the
      level of individual cells and is extensively used in genotoxicity studies. It is
      commonly applied to cultured cells. The aim of this study was to apply the comet
      assay for use in fresh liver tissue, where metabolic activity, all cell types and
      tissue architecture are preserved. The response of liver slices to genotoxic
      agents was tested with the reactive oxygen species generating tert-butyl
      hydroperoxide (tBOOH, 0.1-2 mM), [corrected] and the pro-carcinogens 2-amino-3
      methylimidazo[4,5-f]quinoline (IQ, 0.5-2 mM) and benzo(a)pyrene (BaP, 10-100
      microM). Dose-dependent DNA damage was observed and compared to HepG2 cells. At
      non-cytotoxic concentrations of carcinogens, human liver slices were more
      sensitive to tBOOH than rat liver slices, while no significant difference was
      found for BaP and IQ. Human liver slices were more sensitive to IQ than HepG2
      cells, equally sensitive to BaP and less to tBOOH. Control slices showed low
      levels of DNA damage, which did not increase during 24 h preservation (0 degrees
      C) or 48 h culturing (37 degrees C). In conclusion, the comet assay that we
      applied for measuring DNA damage in precision-cut liver slices is an useful tool
      to study genotoxic effects induced by various potential genotoxicants, allowing
      for detection of species differences in susceptibility to carcinogens.

PMID- 17459657
TI  - Involvement of reactive oxygen species in aclarubicin-induced death of human
      trisomic and diabetic fibroblasts.
AB  - We investigated the mode of cell death induced by aclarubicin in human trisomic
      and diabetic fibroblasts. The cells were incubated with aclarubicin for 2 h and
      then were cultured in drug-free medium for up to 96 h. Aclarubicin in trisomic
      and diabetic fibroblasts, compared with normal cells, induced lesser changes in
      the level of reactive oxygen species (ROS) and the content of intracellular
      calcium. The drug induced ROS-mediated apoptotic and necrotic pathways in all
      cell lines. The extent of apoptosis and necrosis was strongly dependent on the
      cell line, sensitivity to drug and post-treatment time. These results indicate
      that most resistant diabetic cells died prevalently by apoptosis. In the case of
      trisomic fibroblasts, the number of apoptotic cells decreased with post
      incubation time. The role of reactive oxygen species in aclarubicin-induced cell
      death was confirmed by the diminution effects of antioxidants (N-acetylcysteine
      and pyrrolidine-dithiocarbamate) on drug-induced ROS formation, increase of
      intracellular calcium and the extent of apoptosis and necrosis in fibroblast cell
      lines.

PMID- 17459658
TI  - Expression signatures that correlated with Gleason score and relapse in prostate
      cancer.
AB  - Predicting prognosis in prostate carcinoma remains a challenge when using
      clinical and pathologic criteria only. We used an array-based DASL assay to
      identify molecular signatures for predicting prostate cancer relapse in formalin
      fixed, paraffin-embedded (FFPE) prostate cancers, through gene expression
      profiling of 512 prioritized genes. Of the 71 patients that we analyzed, all but
      3 had no evidence of residual tumor (defined as negative surgical margins)
      following radical prostatectomy and no patient received adjuvant therapy
      following surgery. All of the 71 patients had an undetectable serum PSA following
      radical prostatectomy. Follow-up period was 44+/-15 months. Highly reproducible
      gene expression patterns were obtained with these samples (average R(2)=0.99). We
      identified a panel of 11 genes that correlated positively and 5 genes that
      correlated negatively with Gleason grade. A gene expression score (GEX) was
      derived from the expression levels of the 16 genes. We assessed the prognostic
      value of these genes and found the GEX significantly correlated with disease
      relapse (p=0.007). These results suggest that the approach we used is effective
      for expression profiling in heterogeneous FFPE tissues for cancer
      diagnosis/prognosis biomarker discovery and validation.

PMID- 17459659
TI  - Immunization with peptides derived from the idiotypic region of lupus-associated
      autoantibodies delays the development of lupus nephritis in the (SWR x NZB)F1
      murine model.
AB  - Systemic lupus erythematosus (SLE) is a multiorgan autoimmune disease affecting
      40-50/100,000 Americans. Although most of the research on pathogenic antibodies
      focuses on antigenic specificity, there is increasing evidence that specific
      immunoglobulin idiotypes may mediate lupus nephritis independent of autoantigen
      specificity. In previous work, our laboratory characterized a set of
      nephritogenic monoclonal antibodies with substantial idiotypic cross-reactivity,
      produced by the spontaneous SLE model (SWR x NZB)F(1) (SNF(1)), termed
      Id(LN)F(1). Peptides derived from one of these antibodies, Id540, was previously
      shown to stimulate pathogenic T-cells from prenephritic SNF(1) mice, similar to
      what has been seen for pathogenic A6.1 antibody produced by the (NZB x NZW)F(1)
      model. In this study, we immunized pre-nephritic SNF(1) mice with p62-73, a
      peptide derived from the variable region of Id540 and, in separate experiments,
      with p58-69, a peptide derived from the variable region of A6.1. In both cases,
      immunization resulted in increased survival and delayed nephritis; however, while
      both peptides affected levels of anti-DNA antibodies, immunization with p62-73
      only affected levels of Id(LN)F(1) antibodies. These findings confirm the roles
      of pathogenic idiotypes in the pathogenesis of lupus nephritis and suggest that
      therapies that target specific idiotypes might be a potential tool in the
      management of SLE.

PMID- 17459660
TI  - Psychiatric morbidity and X-chromosomal origin in a Klinefelter sample.
AB  - The presence of an additional X-chromosome in Klinefelter patients provides an
      opportunity to study the influence of this chromosome on psychiatric disorders.
      Previous studies have reported an excess of Klinefelter patients in psychiatric
      patient groups. We report an increased prevalence of psychiatric disorders
      including psychotic disorders in a sample of Klinefelter patients but could not
      find evidence of an effect of the parental origin of the extra X-chromosome on
      the psychiatric phenotype. Nevertheless, these findings provide further support
      for the role of the X-chromosome in the susceptibility to psychiatric disorders
      in general and psychotic disorders in particular.

PMID- 17459661
TI  - Facial measurement differences between patients with schizophrenia and non
      psychiatric controls.
AB  - OBJECTIVE: Several previous reports suggest that facial measurements in patients
      with schizophrenia differ from those of non-psychiatric controls. Because the
      face and brain develop in concert from the same ectodermal tissue, the study of
      quantitative craniofacial abnormalities may give clues to genetic and/or
      environmental factors predisposing to schizophrenia. Using a predominantly
      African American sample, the present research question was two-fold: (1) Do
      patients differ from controls in terms of a number of specific facial
      measurements?, and (2) Does cluster analysis based on these facial measurements
      reveal distinct facial morphologies that significantly discriminate patients from
      controls? METHOD: Facial dimensions were measured in 73 patients with
      schizophrenia and related psychotic disorders (42 males and 31 females) and 69
      non-psychiatric controls (35 males and 34 females) using a 25-cm head and neck
      caliper. Due to differences in facial dimensions by gender, separate independent
      samples Student's t-tests and logistic regression analyses were employed to
      discern differences in facial measures between the patient and control groups in
      women and men. Findings were further explored using cluster analysis. Given an
      association between age and some facial dimensions, the effect of age was
      controlled. RESULTS: In unadjusted bivariate tests, female patients differed from
      female controls on several facial dimensions, though male patients did not differ
      significantly from male controls for any facial measure. Controlling for age
      using logistic regression, female patients had a greater mid-facial depth (tragus
      subnasale) compared to female controls; male patients had lesser upper facial
      (trichion-glabella) and lower facial (subnasale-gnathion) heights compared to
      male controls. Among females, cluster analysis revealed two facial morphologies
      that significantly discriminated patients from controls, though this finding was
      not evident when employing further cluster analyses using secondary distance
      measures. When the sample was restricted to African Americans, results were
      similar and consistent. CONCLUSIONS: These findings indicate that, in a
      predominantly African American sample, some facial measurements differ between
      patients with schizophrenia and non-psychiatric controls, and these differences
      appear to be gender-specific. Further research on gender-specific quantitative
      craniofacial measurement differences between cases and controls could suggest
      gender-specific differences in embryologic/fetal neurodevelopmental processes
      underpinning schizophrenia.

PMID- 17459662
TI  - Self-report of attenuated psychotic experiences in a college population.
AB  - This study assessed the rates of self-reported "prodromal" psychotic symptoms and
      related distress in a college population. 1020 students completed the Prodromal
      Questionnaire (PQ), a self-report screening measure for psychosis risk.
      Participants' responses were highly similar to the responses of non-psychotic
      spectrum patients in the original PQ validation sample [Loewy, R.L., Bearden,
      C.E., Johnson, J.K., Raine, A., Cannon, T.D., 2005. The Prodromal Questionnaire
      (PQ): preliminary validation of a self-report screening measure for prodromal and
      psychotic syndromes. Schizophr. Res. 79 (1) 117-125], suggesting that the PQ may
      perform similarly with a variety of populations. Applying the cutoff proposed for
      screening treatment-seeking patients (8 or more positive symptoms) identified 43%
      of students, while comparatively fewer participants (25%) endorsed eight or more
      items at the frequency required for prodromal syndrome diagnosis by interview
      (i.e., weekly), and only 2% endorsed eight or more items as distressing. Although
      attenuated psychotic experiences are commonly reported by "normal" young adults,
      frequent and distressing items identify a proportion of students more consistent
      with the prevalence of psychotic-spectrum disorders in the general population,
      which suggests a potential for future screening of unselected samples.

PMID- 17459663
TI  - The significance of compliance for the success of antimicrobial prophylaxis in
      recurrent lower urinary tract infections: the Greek experience.
AB  - In an attempt to define the most important driver responsible for recurrence of
      cystitis in women, 181 records were retrospectively analysed among 1010
      consecutive references in a tertiary centre for lower urinary tract infections
      (UTIs). All 181 women had more than three episodes of cystitis per year; 129 were
      under continuous prophylaxis and 52 were under postcoital prophylaxis. Analysis
      revealed that the most important factor affecting successful outcome of
      chemoprophylaxis was the compliance of patients (odds ratio 0.074; P<0.0001).
      Among women treated for >or=6 months, the most effective regimen was
      nitrofurantoin, with a success rate of 96.8% compared with 82.8% for
      trimethoprim/sulphamethoxazole and 72.3% for norfloxacin (P=0.046 between
      agents). Failure of chemoprophylaxis was observed in 51 women in total; in 26 of
      them resistance to the administered agent had developed. Results of this
      retrospective study revealed that the most important driver leading to failure of
      prophylaxis for recurrent lower UTIs was the lack of compliance of women with
      their medication. Nitrofurantoin was the most potent among the administered
      agents.

PMID- 17459664
TI  - The effect of amalgam exposure on mercury- and antibiotic-resistant bacteria.
AB  - Antibiotic resistance genes can be found on the same mobile genetic elements as
      genes coding for resistance to metals such as mercury (Hg). Amalgam restorations
      contain ca. 50% Hg and, therefore, it could be expected that exposure to such
      dental restorative materials may promote Hg resistance and thereby antibiotic
      resistance. An in vitro biofilm model was used to grow microcosm dental plaques
      on enamel or amalgam substrata. The number and proportion of Hg-resistant
      organisms over time were determined by viable counts. Microcosm dental plaques
      grown in the presence of amalgam had a higher number and proportion of Hg
      resistant bacteria than those grown on enamel. The levels of these Hg-resistant
      bacteria remained elevated for a period of 48 h, however after 72 h the
      proportions returned to baseline levels. Of the 42 Hg-resistant bacteria
      isolated, 98% were streptococci, with Streptococcus mitis predominating. A high
      proportion of the Hg-resistant isolates (71%) were also resistant to a range of
      antibiotics, with resistance to tetracycline being encountered most frequently.
      The results of this in vitro study indicate that placement of amalgam
      restorations may play a role in promoting the levels of Hg- and antibiotic
      resistant bacteria present in the oral cavity.

PMID- 17459665
TI  - Influence of Haemophilus influenzae beta-lactamase production and/or ftsI gene
      mutations on in vitro activity of and susceptibility rates to aminopenicillins
      and second- and third-generation cephalosporins.

PMID- 17459666
TI  - Dissemination of clonal groups of uropathogenic Escherichia coli is not a
      significant contributor to trimethoprim and sulfamethoxazole resistance in
      Galway, Ireland.

PMID- 17459667
TI  - An in vitro study of the elimination of oseltamivir carboxylate by
      haemofiltration.

PMID- 17459668
TI  - Daptomycin for treatment of patients with bone and joint infections: a systematic
      review of the clinical evidence.
AB  - The treatment of bone and joint infections, mainly caused by Gram-positive
      pathogens, can be difficult and quite challenging since it frequently involves
      prolonged administration of antibiotics as well as appropriate surgical
      procedures. First-line drugs have failed in some cases to cure the underlying
      infection. We performed a systematic review of the available evidence to clarify
      further the effectiveness and safety of daptomycin in the treatment of bone and
      joint infections. Cure of infection was achieved in 43/53 cases (81.1%). The
      results of the reviewed articles are promising with regard to the effectiveness
      and safety profile of this new antibiotic for bone and joint infections that are
      not responsive to other traditionally used antimicrobial agents. Although these
      reports are encouraging, the relatively frequent emergence of antimicrobial
      resistance associated with prolonged administration of daptomycin should be
      considered seriously.

PMID- 17459669
TI  - Platelets: the universal killer?
AB  - For many, the final terminal event in life is cessation of the heart beat. In
      turn, this is generally because this organ has been deprived of oxygen and
      glucose as the blood can no longer deliver these requirements to the myocardium.
      The principal reason for this is blockage of one or more coronary arteries or
      arterioles by platelet rich thrombus. A similar process exists for the
      pathophysiology of stroke--a disabilitating and often fatal event caused by
      occlusion or rupture of arteries in, or feeding, the brain. These scenarios are
      best developed in cardiovascular disease, but apply to almost all human disease.
      Therefore, the ultimate culprit for these major life events is the overactive
      platelet-too ready to form an inappropriate thrombus. Thus, one way forward in
      postponing an occlusive thrombotic event is to minimise platelet activation, new
      tools and treatments for which are eagerly sought.

PMID- 17459670
TI  - TRPC6 and FSGS: the latest TRP channelopathy.
AB  - Focal and segmental glomerulosclerosis (FSGS) is a common cause of nephrotic
      syndrome in children and adults throughout the world. In the past 50 years,
      significant advances have been made in the identification and characterization of
      familial forms of nephrotic syndrome and FSGS. Resultant to these pursuits,
      several podocyte structural proteins such as nephrin, podocin, alpha-actinin 4
      (ACTN4), and CD2-associated protein (CD2AP) have emerged to provide critical
      insight into the pathogenesis of hereditary nephrotic syndromes. The latest
      advance in familial FSGS has been the discovery of a mutant form of canonical
      transient receptor potential cation channel 6 (TRPC6), which causes an increase
      in calcium transients and essentially a gain of function in this cation channel
      located on the podocyte cell membrane. The TRP ion channel family is a diverse
      group of cation channels united by a common primary structure which contains six
      membrane-spanning domains, with both carboxy and amino termini located
      intracellularly. TRP channels are unique in their ability to activate
      independently of membrane depolarization. TRPC6 channels have been shown to be
      activated via phospholipase C stimulation. The mechanisms by which mutant TRPC6
      causes an increase in intracellular calcium and leads to glomerulosclerosis are
      unknown. Mutant TRPC6 may affect critical interactions with the aforementioned
      podocyte structural proteins, leading to abnormalities in the slit diaphragm or
      podocyte foot processes. Mutant TRPC6 may also amplify injurious signals mediated
      by Ang II, a common final pathway of podocyte apoptosis in various mammalian
      species. Current evidence also suggests that blocking TRPC6 channels may be of
      therapeutic benefit in idiopathic FSGS, a disease with a generally poor
      prognosis. Preliminary experiments reveal the commonly used immunosuppressive
      agent FK-506 can inhibit TRPC6 activity in vivo. This creates the exciting
      possibility that blocking TRPC6 channels within the podocyte may translate into
      long-lasting clinical benefits in patients with FSGS.

PMID- 17459671
TI  - Comparison of neurofuzzy logic and decision trees in discovering knowledge from
      experimental data of an immediate release tablet formulation.
AB  - Understanding of the cause-effect relationships between formulation ingredients,
      process conditions and product properties is essential for developing a quality
      product. However, the formulation knowledge is often hidden in experimental data
      and not easily interpretable. This study compares neurofuzzy logic and decision
      tree approaches in discovering hidden knowledge from an immediate release tablet
      formulation database relating formulation ingredients (silica aerogel, magnesium
      stearate, microcrystalline cellulose and sodium carboxymethylcellulose) and
      process variables (dwell time and compression force) to tablet properties
      (tensile strength, disintegration time, friability, capping and drug dissolution
      at various time intervals). Both approaches successfully generated useful
      knowledge in the form of either "if then" rules or decision trees. Although
      different strategies are employed by the two approaches in generating
      rules/trees, similar knowledge was discovered in most cases. However, as decision
      trees are not able to deal with continuous dependent variables, data
      discretisation procedures are generally required.

PMID- 17459672
TI  - [Pediatric aspects of Fabry's disease].
AB  - Fabry's disease is a rare X-linked inborn error of glycosphingolipid metabolism
      characterised by an abnormal lipid storage due to a defect of lysozomal
      alphagalactosidase. The consequence is a storage of glycosphingolipides in all
      tissues. This storage in vessels's endothelial cells is responsible, in males,
      for severe ischemic lesions leading to progressive kidney failure, cardiac and
      cerebral dysfunctions. Similarly, it involves ocular tissues, mainly the cornea,
      the conjunctiva and the lens. The corneal storage, known as cornea verticillata,
      is a clinical marker easy to recognize by slit lamp examination of the affected
      males and carrier females. The enzymatic activity of alphagalactosidase is
      reduced in tears. Characteristic lamellar bodies can be observed by electron
      microscopy study of a conjunctival biopsy. Until recently, treatment was limited
      to symptomatic management of pain, and end-stage complications of renal failure,
      cardiac or brain disease. Recent studies have demonstrated that enzyme
      replacement therapy by genetic engineering is now shown to be promising for
      affected patients.

PMID- 17459673
TI  - [Nebulized drugs: the evolution?].
AB  - The revival of nebulization as a drug delivery route is real. The current
      delivery systems respond to the new European norms, the new mesh-vibrating
      nebulizers allow delivering drugs more quickly, other nebulizers, more performant
      because of less drug losses and of a better lung deposition of the drug, are in
      progress. Only 12 drugs are commercialized for nebulization. All are available in
      dispensaries, some requiring a first prescription by a physician working in a
      hospital (cystic fibrosis drugs), others requiring a prescription from only some
      specialists as paediatricians or pulmonologists (bronchodilators). Works are in
      progress concerning the diameter and shape of the drug particles (nanotechnology)
      and also concerning the use of nebulized drugs for a systemic effect (vaccines,
      insulin, cyclosporine, anticancerous agents, etc.).

PMID- 17459674
TI  - [Evolution of disposable diapers and reduction of diaper dermatitis].
AB  - Keeping babies skin dry in the diaper environment, reducing leaking while
      increasing absorbency and preventing skin pH increase lead to provide better skin
      tolerance disposable diapers. During 80's, basic cellulose diapers were replaced
      by the introduction of absorbent gelling materials (AGM) and since 90's by
      microbreatheable diapers. These advances in diaper technology have contributed to
      the reduction of diaper dermatitis.

PMID- 17459675
TI  - [Antenatal betamethasone during pregnancy with severe diabetes: is better worse
      than good?].
AB  - Diabetic pregnancy is a precarious situation, both for mother and fetus, because
      it increases the risk of prematurity and respiratory distress. We report 3 cases
      of severe acute complications following antenatal betamethasone treatment in
      mothers presenting with severe diabetes. Corticosteroids are strongly recommended
      to prevent prematurity complications in newborns. We highlight the high risk
      profile of theses pregnancies, the effect of this treatment on the mother and the
      child, and question the real benefit of corticotherapy for these fragile
      newborns. The metabolic and blood pressure balance is dangerously disturbed in
      such pregnancies by this treatment. This brings the question of how justified are
      corticosteroids in such cases?

PMID- 17459676
TI  - [The child with fever in pyrins time].

PMID- 17459677
TI  - [Adenovirus infections in children: experience in the field of the allogeneic
      stem cell transplantation].
AB  - Adenovirus (Adv) infections are frequent in pediatric patients, sometimes
      serious, above all in immunocompromised children. We report the cases of 2
      children who presented an Adv infection after allogeneic stem cell
      transplantation (SCT). CASE REPORTS: Case n(o) 1 concerns a boy who received SCT
      at the age of 6 years. He had a hemorragic cystitis, which resolved after
      antiviral treatment and successful engraftment. Case n(o) 2 concerns a boy who
      received SCT at the age of 2. He shortly presented a disseminated infection, and
      died in spite of antiviral treatment and re-infusion of an autologous transplant.
      DISCUSSION: T-cell depletion (mainly carried out in vivo at present) is the major
      risk factor of Adv infection after allogeneic SCT. It is important to be
      recognized, in order to proceed to a routine screening among transplanted
      patients. Moreover, the detection of viral genoma by molecular biology is a
      predictive factor of disseminated disease development, with mortality rates
      higher than 50%. Early treatment is thus crucial. Immunotherapy is to be
      developed, by tapering of immunosuppression, or by manipulating grafts and donor
      lymphocyte infusions, in order to improve Adv specific responses. The possibility
      of a prophylaxis is still to be investigated.

PMID- 17459678
TI  - [Long-term safety of recombinant growth hormone].

PMID- 17459679
TI  - [Stuttering priapism in children with sickle cell anemia in Togo].
AB  - AIM: To describe clinical aspects and outcome of stuttering priapism (SP) in
      children with sickle cell anemia. PATIENTS AND METHODS: We included the 8
      children with sickle cell anemia suffering from SP between 1996 and 2004.
      RESULTS: Age at onset of SP ranged from 5 to 14 years (mean 9.75+/-3.69 years).
      SP attacks occurred once a day for 6 patients, and 2 and 3 times by week for the
      others. It happened during deep sleep, especially in the night (all patients) and
      sometimes in the day (4 patients). The duration of attacks ranged from 10 min to
      2 h in 6 patients and 4 to 5 h in 2 patients. Oral etilefrine was administered to
      all patients until the cessation of attacks, and continued during 1 month. A long
      remission was obtained in all patients after 7 days to 7 months treatment (follow
      up 2 to 7 years) in spite of 1 or many relapses.

PMID- 17459680
TI  - Hypofractionation in clinical trials for prostate cancer.

PMID- 17459681
TI  - Vascular damaging agents.
AB  - To provide a comprehensive overview on vascular targeting agents and the
      application of radiobiological principles in pre-clinical and clinical studies,
      we completed a comprehensive review of published medical studies on vascular
      targeting agents using Pub Med. Vascular targeting agents are now divided into
      vascular disrupting agents (VDAs), which target the pre-existing tumour
      vasculature, and angiogenesis inhibitors (AIs), which prevent the formation of
      new blood vessels. Modest success has been seen when VDAs and AIs are used as
      single agents and therefore combination therapies that can work in a
      complimentary and synergistic manner, targeting both the tumour cells and
      endothelial cells, are needed. Radiobiological principles have been used to
      increase our understanding of these agents, and can explain the increased
      efficacy of combination treatments. In particular, the alteration of the tumour
      microenvironment by AIs and VDAs can lead to enhanced efficacy when combined with
      chemotherapy or radiotherapy, with phase II/III trials showing encouraging
      results. The optimal use and scheduling of AIs and VDAs remains to be determined.
      Further understanding of the mechanisms of action of these potentially very
      exciting anti-neoplastic agents is urgently required.

PMID- 17459682
TI  - Effects of cinnamene enhancers on transdermal delivery of ligustrazine
      hydrochloride.
AB  - Cinnamene compounds, cinnamic acid, cinnamaldehyde and cinnamic alcohol, were
      employed as enhancers. The effects and mechanisms of penetration promoters on the
      in vitro percutaneous absorption of ligustrazine hydrochloride across hairless
      porcine dorsal skin were investigated. Transdermal fluxes of ligustrazine
      hydrochloride through porcine skin were determined in vitro by Franz-type
      diffusion cells. The results indicated that the penetration flux of ligustrazine
      hydrochloride by cinnamic acid was the greatest. Significant statistical
      differences (P<0.05) were found between cinnamic acid and other promoters.
      Fourier transform-infrared (FT-IR) were carried out to analyze the effects of
      enhancers on the biophysical properties of the stratum corneum and the permeation
      enhancement mechanisms. FT-IR results revealed that the changes of peak shift and
      peak area due to C-H stretching vibrations in the stratum corneum lipids were
      associated with the selected enhancers. All of them could perturb and extract the
      stratum corneum lipids to different extent. Morphological changes of the skin
      treated with enhancers were monitored by a scanning electron microscope. It was
      demonstrated that the extraction of the stratum corneum lipids by the enhancers
      led to the disruption of stratum corneum and the desquamation of stratum corneum
      flake. Apparent density was newly proposed to estimate the desquamated extent of
      stratum corneum flake. Correlation analysis revealed that there was a linear
      relationship between apparent density and decrease in peak area. The results
      showed that the permeation enhancement mechanisms of cinnamene were pleiotropic
      ones, including disordering the lipids, extracting the lipids and competitive
      hydrogen bonding between cinnamene enhancers and amides of ceramide head groups
      in stratum corneum.

PMID- 17459683
TI  - Evidence that drug flux across synthetic membranes is described by normally
      distributed permeability coefficients.
AB  - Over recent decades, the use of in vitro diffusion cell studies to assess skin
      permeability has evolved into a major research tool, providing key insights into
      the relationships between skin, drug and formulation. Sometimes, such studies
      involve synthetic membranes as this approach can yield useful inferences with
      respect to drug-skin partitioning and diffusion phenomena. Yet despite the
      popularity of such studies, it is still not at all known whether typical solute
      transport across synthetic barriers results in a normal distribution of
      permeability coefficients or alternatively some type of skewed distribution. The
      present study aims to shed light on this issue. To this end, five compounds
      (testosterone, oestradiol, corticosterone, aldosterone and adenosine) exhibiting
      a broad range of octanol-water partition coefficient values were selected as test
      penetrants. The protocol involved taking multiple replicate measurements of each
      drug's passive steady state flux through poly(dimethylsiloxane) membrane. Each
      penetrant's resultant permeability coefficient database was subjected to a
      Kolmogorov-Smirnov (KS) test for normality. It was found that the permeability
      coefficients of all five drugs were distributed in a Gaussian-normal fashion. The
      theoretical significance and practical impact of these findings are discussed.

PMID- 17459684
TI  - Quantitative detection of the oil-degrading bacterium Acinetobacter sp. strain
      MUB1 by hybridization probe based real-time PCR.
AB  - Quantitative detection of the oil-degrading bacterium Acinetobacter sp. strain
      MUB1 was performed using the SoilMaster() DNA Extraction Kit (Epicentre, Madison,
      Wisconsin) and hybridization probe based real-time PCR. The detection target was
      the alkane hydroxylase gene (alkM). Standard curve construction showed a linear
      relation between log values of cell concentrations and real-time PCR threshold
      cycles over five orders of magnitude between 5.4+/-3.0x10(6) and 5.4+/
      3.0x10(2)CFUml(-1) cell suspension. The detection limit was about 540CFUml(-1),
      which was ten times more sensitive than conventional PCR. The quantification of
      Acinetobacter sp. strain MUB1 cells in soil samples resulted in 46.67%, 82.41%,
      and 87.59% DNA recovery with a detection limit of 5.4+/-3.0x10(4)CFUg(-1) dry
      soil. In this study, a method was developed for the specific, sensitive, and
      rapid quantification of the Acinetobacter sp. strain MUB1 in soil samples.

PMID- 17459685
TI  - Keratinolytic activity of Bacillus megaterium F7-1, a feather-degrading
      mesophilic bacterium.
AB  - The aim of this study was to investigate environmental conditions affecting
      chicken feather degradation and keratinolytic enzyme production by Bacillus
      megaterium F7-1, a feather-degrading mesophilic bacterium. B. megaterium F7-1
      degraded whole chicken feather completely within 7 days. The bacterium grew with
      an optimum at pH 7.0-11.0 and 25-40 degrees C, where maximum keratinolytic
      activity was also observed. The production of keratinolytic enzyme by B.
      megaterium F7-1 was inducible with feather. Keratinolytic enzyme production by B.
      megaterium F7-1 at 0.6% (w/v) skim milk was 468U/ml, which was about 9.4-fold
      higher than that without skim milk. The amount of keratinolytic enzyme production
      depended on feather concentrations. The degradation rate of autoclaved chicken
      feathers by cell-free culture supernatant was 26% after 24h of incubation, but
      the degradation of untreated chicken feathers was unsuccessful. B. megaterium F7
      1 effectively degraded feather meal, duck feather and human nail, whereas human
      hair and sheep wool showed relatively low degradation rates. B. megaterium F7-1
      presented high keratinolytic activity and was very effective in feather
      degradation, providing potential use for biotechnological processes of keratin
      hydrolysis.

PMID- 17459686
TI  - Quantitative isolation of biocontrol agents Trichoderma spp., Gliocladium spp.
      and actinomycetes from soil with culture media.
AB  - Soil biodiversity plays a key role in the sustainability of agriculture systems
      and indicates the level of health of soil, especially when considering the
      richness of microorganisms that are involved in biological control of soilborne
      diseases. Cultural practices may produce changes in soil microflora, which can be
      quantified through the isolation of target microorganisms. Rhizosphere soil
      samples were taken from an assay with different crop rotations and tillage
      systems, and populations of Trichoderma spp., Gliocladium spp. and actinomycetes
      were quantified in order to select the general and selective culture media that
      better reflect the changes of these microbial populations in soil. The most
      efficient medium for the isolation of Trichoderma spp. and Gliocladium spp. was
      potato dextrose agar modified by the addition of chloramphenicol, streptomycin
      and rose bengal, and for actinomycetes was Kuster medium, with cycloheximide and
      sodium propionate.

PMID- 17459687
TI  - Electrochemical catalysis and thermal stability characterization of laccase
      carbon nanotubes-ionic liquid nanocomposite modified graphite electrode.
AB  - The hydrophobic carbon nanotubes-ionic liquid (CNTs-IL) gel forms a stable
      modified film on hydrophobic graphite electrode surface. Laccase immobilized on
      the CNTs-IL gel film modified electrode shows good thermal stability and enhanced
      electrochemical catalytic ability. The optimal bioactivity occurs with increasing
      temperature and this optimum is 20 degrees C higher in comparison to free
      laccase. The improvement of laccase thermal stability may be due to the
      microenvironment of hydrophobic CNTs-IL gel on graphite electrode surface. On the
      other hand, the sensitive detection of oxygen has been achieved due to the
      feasibility of oxygen reduction by both of laccase and nanocomposite of CNTs-IL
      gel. Furthermore, the laccase hybrid nanocomposite also shows the fast
      electrochemical response and high sensitivity to the inhibitors of halide ions
      with the approximate IC50 of 0.01, 4.2 and 87.5 mM for the fluoride, chloride and
      bromide ions, respectively. It implies the feasibility of laccase modified
      electrode as an inhibition biosensor to detect the modulators of laccase.

PMID- 17459688
TI  - Identifying CSF using urine glucose dipstick testing.

PMID- 17459689
TI  - Labour analgesia and scabies.

PMID- 17459690
TI  - Total intravenous anesthesia for evacuation of a hydatidiform mole and
      termination of pregnancy in a patient with thyrotoxicosis.
AB  - Clinical hyperthyroidism is found in approximately 5% of women with a
      hydatidiform mole, as human chorionic gonadotropin secreted by molar tissue is
      structurally similar to thyroid-stimulating hormone. A hydatidiform mole
      occasionally presents with a co-existing viable fetus. Surgical evacuation may be
      indicated for significant hemorrhage or preeclampsia. Perioperative management in
      the presence of hyperthyroidism may be complicated by a thyroid storm. We report
      a case of total intravenous anesthesia with propofol and remifentanil, combined
      with an esmolol infusion, to control sympathetic hyperactivity during surgery.

PMID- 17459692
TI  - Epidural anesthesia for cesarean section in a parturient with subaortic stenosis.

PMID- 17459691
TI  - Intravenous patient-controlled analgesia for labour: a survey of UK practice.
AB  - BACKGROUND: Although regional techniques offer superior analgesia during labour,
      many women receive other methods of pain relief. Furthermore, there is a specific
      need for analgesia in a small population of labouring women for whom regional
      techniques are contraindicated, unavailable or impossible to perform. We surveyed
      current UK practice of labour analgesia for such patients, with particular
      reference to the use of intravenous patient-controlled analgesia. METHODS:
      Following approval from the Obstetric Anaesthetists' Association, a questionnaire
      was sent to the lead anaesthetic consultants of 243 obstetric units in the United
      Kingdom. The questionnaire evaluated the availability of methods of pain relief
      other than regional blocks. Information was sought on patient-controlled
      intravenous analgesia regimens and patient monitoring. RESULTS: A total of 159
      questionnaires were returned giving a response rate of 65.4%. The majority of
      units that responded (95.5%) used either intramuscular pethidine or diamorphine.
      Nearly half (49%) offered patient-controlled intravenous analgesia for labour
      pain. One third of units (36%) had an analgesic protocol for women in whom
      regional anaesthetic techniques were contraindicated. With patient-controlled
      intravenous analgesia, remifentanil (34.6%) was the most commonly used opioid for
      live births while morphine (35.5%) was used more commonly for deliveries
      involving intrauterine deaths. CONCLUSION: The survey demonstrated that, when
      regional techniques were contraindicated, patient-controlled intravenous opioid
      analgesia was employed in almost half of the units responding to the
      questionnaire.

PMID- 17459693
TI  - Gerard W. Ostheimer Lecture 2006: What's New in Obstetric Anaesthesia?
      Contributions from the 2005 literature.
AB  - The Gerard W. Ostheimer lecture is given every year at the annual meeting of the
      Society for Obstetric Anesthesia and Perinatology by an obstetric
      anaesthesiologist who has reviewed the scientific literature for the previous
      calendar year. This article is based on the 2006 Ostheimer lecture and reviews
      three areas of interest in neonatology: resuscitation of the newborn, neonatal
      encephalopathy and the influence of epidural analgesia on breastfeeding.

PMID- 17459694
TI  - Examining the influence of maternal bradycardia on neonatal outcome using
      automated data collection.
AB  - BACKGROUND: Due to the increasing number of caesarean sections, we investigated
      the influence of maternal bradycardia during general and regional anaesthesia on
      seven standard paediatric outcome parameters using our online recorded data.
      METHODS: Data from 1154 women undergoing caesarean section were investigated
      prospectively. Bradycardia was defined as a heart rate below 60 beats/min. The
      matched-pairs method was used to evaluate the impact of bradycardia on Apgar
      scores at 1, 5, and 10 min, umbilical artery pH and base excess, admission to
      paediatric intensive care unit, and seven-day mortality. Matched references were
      automatically selected among all patients from the data pool according to
      anaesthetic technique, sensory block height, urgency, maternal age and body mass
      index. Stepwise regression models were developed to predict the impact of intra
      operative bradycardia on outcome variables with differences between matched pairs
      assessed using univariate analysis. RESULTS: Bradycardia was found in 146 women
      (12.7%) for whom a control could be matched in 131 cases (89.7%). Mean 5-minute
      Apgar score was 9.2+/-1.1 for study patients and 9.3+/-1.1 for controls. pH and
      base excess were not significantly different between groups. In cases of urgent
      surgery, neonates had an increased risk of 1.8 (95% CI 1.36-2.44, P<0.01) for an
      Apgar score <or= 8 at 1 min and a 2.6-fold risk (95% CI 1.64-4.06, P<0.01) of
      umbilical arterial pH of <or= 7.2 compared to infants undergoing non-urgent
      procedures. CONCLUSIONS: Using matched-pairs analysis we were unable to
      demonstrate that episodes of maternal bradycardia below 60 beats/min were
      associated with a poorer neonatal outcome regardless of anaesthetic technique.

PMID- 17459695
TI  - A randomized study of the effects of preoperative ketorolac on general
      anaesthesia for caesarean section.
AB  - BACKGROUND: Ketorolac may attenuate the maternal stress response to tracheal
      intubation, while avoiding opioid-induced neonatal depression. We aimed to
      evaluate the haemodynamic and hormonal effects of prophylactic ketorolac on
      surgical stress and analgesia after caesarean delivery. METHODS: After ethical
      approval, 90 patients scheduled for elective caesarean delivery were randomly
      allocated receive either ketorolac 15 mg i.v. bolus 20 min before induction,
      followed by an infusion of 7.5 mg/h (n=45), or saline placebo (n=45). Anaesthesia
      was maintained with 50% nitrous oxide in oxygen with 0.5% isoflurane.
      Haemodynamic variables, plasma cortisol concentrations, uterine relaxation, need
      for supplementary doses of oxytocin, peri-operative blood loss, haematocrit,
      Apgar scores at 1 and 5 min, postoperative pain scores at rest and movement, and
      tramadol consumption were recorded. RESULTS: After induction, patients receiving
      ketorolac had a smaller increase in heart rate, systolic and mean arterial blood
      pressure (P<0.001) and lower plasma cortisol concentrations, (32.2+/-7.61 vs.
      45+/-15.1 microg/dL, P<0.05), lower pain scores at rest and movement for the
      first two postoperative hours (P<0.001) and a longer time to first request for
      analgesia. Fewer patients in the ketorolac group received tramadol in the four
      hours after surgery (7 (15.6%) vs. 14 (31.1%), P=0.004). There were no
      differences between groups in peri-operative blood loss, vomiting or Apgar
      scores. There was no echocardiographic evidence of premature closure of the
      ductus arteriosus in the newborns. CONCLUSION: Prophylactic ketorolac is safe and
      effective in attenuating the maternal stress response to intubation and improves
      the quality of analgesia after caesarean delivery.

PMID- 17459696
TI  - Health behaviours in childhood cancer survivors: a systematic review.
AB  - AIM: To review (1) prevalence and predictors of risk behaviours especially
      smoking and (2) values of interventions to reduce risk behaviours in childhood
      cancer survivors. METHOD: A systematic search of four databases (OVID Medline
      (1966 to May week 2, 2006), CINAHL, EMBASE, and Pubmed (US Library of Medicine
      and National Institute of Health)) for articles published between January 1990
      and May 2006. RESULTS: Twenty-three eligible articles. Incidence of risk
      behaviours are comparable with, or lower than the general population and
      controls. Socio-demographic (age, socio-economic status, diagnosis, ethnic group)
      and psychological variables (perceived vulnerability) predict risk behaviour.
      Improved knowledge and awareness of vulnerability have been found after
      interventions, but no changes in health behaviours. CONCLUSION: This review
      illustrates an optimistic picture of low participation in substance use amongst
      survivors, although based mainly on smoking. However, smoking might not be the
      major problem for survivors and attention must also be directed to other health
      behaviours including exercise and healthy diet.

PMID- 17459697
TI  - Progesterone receptor mRNA expression and distribution in the female rabbit
      brain.
AB  - Progesterone regulates diverse functions in the rabbit brain through the
      interaction with its nuclear receptor (PR). Although PR protein has been detected
      in some regions of the rabbit forebrain, PR mRNA expression and distribution in
      the rabbit brain are unknown. Hence, we investigated these issues by in situ
      hybridization. New Zealand adult female rabbits were ovariectomized and treated
      with vehicle or estradiol (5 microg/(kg day)) for 3 days. The results show an
      extended distribution of PR mRNA expression in the rabbit brain. The highest
      expression was detected in preoptic area and hypothalamic anterior nuclei such as
      paraventricular, periventricular and arcuate nuclei. A high expression was also
      detected in thalamic and telencephalic areas, including hippocampus and cerebral
      cortex. Estradiol treatment induced an increase in PR mRNA expression in many
      brain areas, particularly in the hippocampus and the hypothalamic and preoptic
      area regions. The wide distribution of PR mRNA in the rabbit brain suggests that
      progesterone through PR activation is involved in several functions apart from
      reproductive behavior in rabbits, and that PR expression is up-regulated by
      estradiol in the rabbit brain.

PMID- 17459698
TI  - Endogenous inhibitors (GALFs) of 11beta-hydroxysteroid dehydrogenase isoforms 1
      and 2: derivatives of adrenally produced corticosterone and cortisol.
AB  - Two isoforms of 11beta-HSD exist; 11beta-HSD1 is bi-directional (the reductase
      usually being predominant) and 11beta-HSD2 functions as a dehydrogenase,
      conferring kidney mineralocorticoid specificity. We have previously described
      endogenous substances in human urine, "glycyrrhetinic acid-like factors (GALFs)",
      which like licorice, inhibit the bi-directional 11beta-HSD1 enzyme as well as the
      dehydrogenase reaction of 11beta-HSD2. Many of the more potent GALFs are derived
      from two major families of adrenal steroids, corticosterone and cortisol. For
      example, 3alpha5alpha-tetrahydro-corticosterone, its derivative, 3alpha5alpha
      tetrahydro-11beta-hydroxy-progesterone (produced by 21-deoxygenation of
      corticosterone in intestinal flora); 3alpha5alpha-tetrahydro-11beta-hydroxy
      testosterone (produced by side chain cleavage of cortisol); are potent inhibitors
      of 11beta-HSD1 and 11beta-HSD2-dehydrogenase, with IC50's in range 0.26-3.0
      microM, whereas their 11-keto-3alpha5alpha-tetrahydro-derivatives inhibit 11beta
      HSD1 reductase, with IC50's in range 0.7-0.8 microM (their 3alpha5beta
      derivatives being completely inactive). Inhibitors of 11beta-HSD2 increase local
      cortisol levels, permitting it to act as a mineralocorticoid in kidney.
      Inhibitors of 11beta-HSD1 dehydrogenase/11beta-HSD1 reductase serve to adjust the
      set point of local deactivation/reactivation of cortisol in vascular and other
      glucocorticoid target tissues, including adipose, vascular, adrenal tissue, and
      the eye. These adrenally derived 11-oxygenated C21- and C19 -steroidal substances
      may serve as 11beta-HSD1- or 11beta-HSD2-GALFs. We conclude that adrenally
      derived products are likely regulators of local cortisol bioactivity in humans.

PMID- 17459699
TI  - Removal of benzene and toluene by carbonized bamboo materials modified with TiO2.
AB  - Carbonized moso bamboo (Phyllostachys pubescens) was coated with TiO(2)
      nanoparticles to enhance its removal efficiency of harmful gases. Carbonized
      bamboo-TiO(2) composite (CBC) was prepared by heating mixtures of carbonized
      bamboo powder (CB) and TiO(2) nanoparticles, denoted as CBM, under nitrogen
      condition. TiO(2) nanoparticle and carbonized bamboo powder were mixed with the
      mass ratios of 1/1 and 2/1, respectively. At the same mass ratio of TiO(2) to CB,
      the benzene and toluene removal efficiencies follow the trend: CBC>CBM>CB, which
      is consistent with the amount of TiO(2) validated by elemental analysis. Sorption
      mechanism of benzene and toluene by CB, CBM and CBC might belong to hydrophobic
      hydrophobic interaction, observed by depletion of untreated bamboo (UB)
      carbohydrates during carbonization. Sorption kinetics was further analyzed, and
      optimal correlation was found by fitting with the Elovich kinetic equation.

PMID- 17459700
TI  - Production and recovery of an alkaline exo-polygalacturonase from Bacillus
      subtilis RCK under solid-state fermentation using statistical approach.
AB  - The empirical models developed through two independent RSM (RSM-I, 2(3); RSM-II,
      2(5)) in terms of effective operational factors of inoculum age, inoculum volume,
      wheat bran-to-moisture ratio (RSM-I) and contact time, extraction temperature,
      agitation, fermented bran-to-solvent ratio and SDS (RSM-II) were found adequate
      to describe the optimization of exo-polygalacturonase from Bacillus subtilis RCK
      under solid-state fermentation (SSF) conditions. Through the analysis of RSM-I,
      wheat bran-to-moisture ratio and inoculum volume were found to be the most
      significant factors and an increment in both had a positive effect in enhancing
      enzyme yield, while in RSM-II all the factors significantly affected enzyme
      recovery except fermented bran-to-solvent ratio, which had the least impact
      within the ranges investigated in enhancing enzyme recovery. Based on contour
      plots and variance analysis, optimum operational conditions for maximum exo
      polygalacturonase yield were achieved when 1.5% (v/w) of 24h old (OD(600 nm)
      approximately 2.7+/-0.2) B. subtilis RCK cells were inoculated on moistened wheat
      bran (1:7 solid substrate-to-moisture ratio) and enzyme was harvested by addition
      of solvent (1:6 fermented bran-to-solvent ratio) under shaking conditions (200
      rpm) in presence of SDS (0.25% w/v) for 15 min at 35 degrees C. An over all 3.4
      fold (1.7-fold RSM-I; 2.0 fold RSM-II) increase in enzyme production was attained
      because of optimization by RSM.

PMID- 17459701
TI  - Bis[(para-methoxy)benzyl] phosphonate prodrugs with improved stability and
      enhanced cell penetration.
AB  - A series of substituted bis[(para-methoxy)benzyl] (bisPMB) esters of 1
      naphthalenemethylphosphonate (NMPA) were synthesized and evaluated as phosphonate
      prodrugs. BisPMB NMPA esters (4b and 4c) with significantly improved aqueous
      stability were identified that also resulted in increased intracellular levels of
      NMPA following prodrug incubation with primary rat hepatocytes.

PMID- 17459702
TI  - Discovery of new C3aR ligands. Part 2: amino-piperidine derivatives.
AB  - The synthesis and structure-activity relationships against the C3a receptor of a
      series of substituted aminopiperidine derivatives are reported. DMPK properties
      and functional activities of selected compounds are described. The compounds
      obtained are the first non-arginine ligands of C3aR.

PMID- 17459703
TI  - Synthesis and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK)
      inhibitors.
AB  - The development of a series of novel aminopyrimidines as inhibitors of c-Jun N
      terminal kinases is described. The synthesis, in vitro inhibitory values for
      JNK1, JNK2 and CDK2, and the in vitro inhibitory value for a c-Jun cellular assay
      are discussed.

PMID- 17459704
TI  - Synthesis and antibacterial activity of derivatives of 6-O-allylic acylides.
AB  - A series of novel acylide derivatives have been synthesized from erythromycin A
      via a facile procedure. By applying this procedure, cyclic carbonation to C-11,12
      position, acylation to C-3 hydroxyl, and deprotection provided the desired
      acylides. These compounds showed antibacterial activity against both macrolide
      susceptible strains and macrolide-resistant strains. Because of existence of 6-O
      allyl substitution, these derivatives can be used as intermediates for further
      structural modification.

PMID- 17459705
TI  - Novel inhibitors of fatty acid amide hydrolase.
AB  - A class of bisarylimidazole derivatives are identified as potent inhibitors of
      the enzyme fatty acid amide hydrolase (FAAH). Compound 17 (IC(50)=2 nM) dose
      dependently (0.1-10mg/kg, iv) potentiates the effects of exogenous anandamide (1
      mg/kg, iv) in a rat thermal escape test (Hargreaves test), and shows robust
      antinociceptive activity in animal models of persistent (formalin test) and
      neuropathic (Chung model) pain. Compound 17 (20 mg/kg, iv) demonstrates activity
      in the formalin test that is comparable to morphine (3mg/kg, iv), and is dose
      dependently inhibited by the CB1 antagonist SR141716A. In the Chung model,
      compound 17 shows antineuropathic effects similar to high-dose (100 mg/kg)
      gabapentin. FAAH inhibition shows potential utility for the clinical treatment of
      persistent and neuropathic pain.

PMID- 17459706
TI  - C(4)-alkyl substituted furanyl cyclobutenediones as potent, orally bioavailable
      CXCR2 and CXCR1 receptor antagonists.
AB  - A novel series of cyclobutenedione centered C(4)-alkyl substituted furanyl
      analogs was developed as potent CXCR2 and CXCR1 antagonists. Compound 16 exhibits
      potent inhibitory activities against IL-8 binding to the receptors (CXCR2 Ki=1
      nM, IC(50)=1.3 nM; CXCR1 Ki=3 nM, IC(50)=7.3 nM), and demonstrates potent
      inhibition against both Gro-alpha and IL-8 induced hPMN migration (chemotaxis:
      CXCR2 IC(50)=0.5 nM, CXCR1 IC(50)=37 nM). In addition, 16 has shown good oral
      pharmacokinetic profiles in rat, mouse, monkey, and dog.

PMID- 17459707
TI  - Reliability and comparison of electromyographic and kinetic measurements during a
      standing reach task in children with and without cerebral palsy.
AB  - The purposes of this study of children with cerebral palsy (CP) and with typical
      development (TD) were to determine: (1) within session test-retest reliability of
      electromyography (EMG) of postural muscles [using motor coordination patterns
      (cMCP)] and center of pressure (COP) measures, (2) relationships between cMCP and
      COP measures, and (3) differences between children with CP and with TD. Data were
      collected twice during a standing reach task in 20 pairs of age and gender
      matched children, 8-14-years-old. Test-retest reliability was poor for cMCPs
      (kappa=0.16-0.21), but good for kinetic measures (ICC=0.69-0.87). Both groups
      demonstrated strong reliance on anterior-posterior neuromuscular control with
      greater variability in the children with CP. The group with TD showed greater
      control in anterior-posterior COP movements than did the group with CP. Anterior
      posterior COP measures were associated with more effective cMCPs in both groups.
      These data support the concept of the center of gravity as a potential control
      parameter working with a flexible neuromuscular system for postural control.

PMID- 17459708
TI  - The energetics of human walking: is Froude number (Fr) useful for metabolic
      comparisons?
AB  - Velocity and body mass have well-known influences on the amount of metabolic
      energy that animals require to walk. This relationship could stem from the fact
      that both are key variables in calculating the mechanical energy of a system in
      motion. Other variables, like leg length, are also important in mechanical energy
      calculations and two mechanical formulations that incorporate leg length, Froude
      number (Fr) and the LiMb model, have been shown to correlate with human metabolic
      energy expenditure. Both, however, include velocity as a key variable in their
      calculations, so we wondered if the correlation might derive solely from their
      relationship with velocity rather than leg length. Using the energetic data and
      gait parameters from 24 human adults and 48 children, we tested several variables
      - velocity (V), V(2), body mass, leg length, Fr and LiMb - to see which
      combinations best explained the variation in oxygen consumption, a proxy of
      metabolic energy expenditure. An equation with V(2), body mass and leg length as
      covariates produced the highest R(2), explaining 88% of the variation when all
      subjects were combined. No significant differences in the predictive power of
      velocity, V(2), Fr or LiMb were detected, prompting us to conclude that neither
      Fr nor LiMb compensate for the effect of leg length. Leg length does influence
      the energetic expenditure of walking humans, but Fr and LiMb do not appear to
      adequately reflect that effect. The development of another method to compensate
      for the effect of leg length on metabolic energy consumption is essential.

PMID- 17459709
TI  - Complete 3D kinematics of upper extremity functional tasks.
AB  - Upper extremity (UX) movement analysis by means of 3D kinematics has the
      potential to become an important clinical evaluation method. However, no
      standardized protocol for clinical application has yet been developed, that
      includes the whole upper limb. Standardization problems include the lack of a
      single representative function, the wide range of motion of joints and the
      complexity of the anatomical structures. A useful protocol would focus on the
      functional status of the arm and particularly the orientation of the hand. The
      aim of this work was to develop a standardized measurement method for
      unconstrained movement analysis of the UX that includes hand orientation, for a
      set of functional tasks for the UX and obtain normative values. Ten healthy
      subjects performed four representative activities of daily living (ADL). In
      addition, six standard active range of motion (ROM) tasks were executed. Joint
      angles of the wrist, elbow, shoulder and scapula were analyzed throughout each
      ADL task and minimum/maximum angles were determined from the ROM tasks.
      Characteristic trajectories were found for the ADL tasks, standard deviations
      were generally small and ROM results were consistent with the literature. The
      results of this study could form the normative basis for the development of a 'UX
      analysis report' equivalent to the 'gait analysis report' and would allow for
      future comparisons with pediatric and/or pathologic movement patterns.

PMID- 17459710
TI  - Ossification of the ligamentum flavum: diet and genetics.
AB  - Ossified ligamentum flavum (OLF) is being appreciated as an important cause of
      thoracic myeloradiculopathy. However, despite numerous epidemiological and basic
      science studies, the pathogenesis of OLF has not been conclusively established.
      Ossification and symptom development are significantly more frequent in the
      Japanese population, therefore supporting a genetic predilection for the disease
      process. We present an unusual case of OLF in a patient from a low-risk genetic
      background (Chinese), exposed in youth to a lifestyle and diet from a high-risk
      population (Japanese). Based on our case report, we support the view that dietary
      habits may constitute an independent risk factor for OLF and ossification of the
      posterior longitudinal ligament.

PMID- 17459711
TI  - 7-Substituted-melatonin and 7-substituted-1-methylmelatonin analogues: effect of
      substituents on potency and binding affinity.
AB  - A series of 7-substituted melatonin and 1-methylmelatonin analogues were prepared
      and tested against human and amphibian melatonin receptors. 7-Substituents
      reduced the agonist potency of all the analogues in the Xenopus laevis
      melanophore assay, 7-bromomelatonin (5d) and N-butanoyl 7-bromo-5
      methoxytryptamine (5f) being the most active compounds, but both were 42-fold
      less potent than melatonin (1). Whereas all the analogues bind with lower
      affinity at the human MT(1) receptor than melatonin, 5d, 5f and N-propanoyl 7
      bromo-5-methoxytryptamine (5e) show a similar binding affinity to melatonin at
      the MT(2) receptor and consequently show some MT(2) selectivity. These results
      suggest that the receptor pocket around C-7 favours binding by an electronegative
      group, suggesting an electropositive region in this area of the receptor.

PMID- 17459712
TI  - Fmoc-protected iminosugar modified asparagine derivatives as building blocks for
      glycomimetics-containing peptides.
AB  - CSF114(Glc) is the first synthetic Multiple Sclerosis Antigenic Probe able to
      identify autoantibodies in a statistically significant number of Multiple
      Sclerosis patients. The beta-turn conformation of this glucopeptide is
      fundamental for a correct presentation of the epitope Asn(Glc). To verify the
      influence of sugar mimics in antibody recognition in Multiple Sclerosis, we
      synthesized Fmoc-protected Asn derivatives containing alkaloid-type sugar mimics.
      The corresponding glycomimetics-containing peptide derivatives of the CSF114-type
      sequence were tested in competitive and solid-phase non-competitive ELISA on
      Multiple Sclerosis patients' sera.

PMID- 17459713
TI  - Purification by ozonolysis of (18)O enriched water after cyclotron irradiation
      and the utilization of the purified water for the production of [18F]-FDG (2
      deoxy-2-[18F]-fluoro-d-glucose).
AB  - The high cost of virgin (18)O-enriched water has forced many researchers to study
      methods to purify and recycle enriched water after the first irradiation for the
      production of radiopharmaceuticals. In our study, [(18)O]H(2)O was purified by
      ozonolysis and distillation. Analyses showed a large decrease in impurities after
      this treatment. The purification procedure was carried out after the production
      of 94 batches of [18F]-FDG, which were manufactured using a GE Minitrace
      cyclotron and a GE Mx TracerLab synthesizer. Saturation yields after bombardment,
      using virgin and re-purified water were, respectively, 2864+/-204MBq/muA and
      2727+/-167MBq/muA, a decrease of 5.5%. The decrease in [18F]-FDG yield, from
      67.2+/-0.7% to 65.5+/-0.9%, can be ascribed to the irradiation step only.

PMID- 17459714
TI  - Multi-element analysis of pyrite ores using polarized energy-dispersive X-ray
      fluorescence spectrometry.
AB  - X-ray fluorescence (XRF) spectrometry is used worldwide in geological material
      analysis. This study, applies polarized energy-dispersive X-ray fluorescence
      (PEDXRF) Spectrometer and compares in the samples of Rize-Cayeli and Mardin
      pyrite ores. The samples of pyrite ore were collected from the Rize and Mardin in
      Turkey. The prepared samples were analyzed using a PEDXRF spectrometer. The
      result of the analysis shows the presence of many elements including rare-earth
      elements (from Na to Th). The accuracy and precision of the technique for
      chemical analysis is demonstrated by analyzing USGS standards, GEOL, GBW 7109 and
      GBW-7309 sediment.

PMID- 17459715
TI  - Thermal neutron diffusion cooling in wet quartz (Monte Carlo simulations of the
      pulsed neutron experiments).
AB  - The thermal neutron diffusion parameters of a rock material depend on the rock
      matrix itself and on the water content. The effect has been studied in quartz by
      Monte Carlo (MC) simulations of the variable buckling experiment for nine series
      of samples. A hyperbolic dependence of the density-removed diffusion cooling
      coefficient on the water content shows a variability of this parameter by two
      orders of magnitude. The function obtained for wet quartz is compared with the
      analogous dependence for wet dolomite.

PMID- 17459716
TI  - Transitory glutathione deficit during brain development induces cognitive
      impairment in juvenile and adult rats: relevance to schizophrenia.
AB  - Glutathione (GSH) metabolism dysfunction is one risk factor in schizophrenia. A
      transitory brain GSH deficit was induced in Wistar (WIS) and mutant (ODS; lacking
      ascorbic acid synthesis) rats using BSO (l-buthionine-(S,R)-sulfoximine) from
      post-natal days 5-16. When GSH was re-established to physiological levels,
      juvenile BSO-ODS rats were impaired in the water maze task. Long after treatment
      cessation, adult BSO-WIS/-ODS rats showed impaired place discrimination in the
      homing board with distributed visual or olfactory cues. Their accuracy was
      restored when a single cue marked the trained position. Similarly, more working
      memory errors were made by adult BSO-WIS in the radial maze when several
      olfactory cues were present. These results reveal that BSO rats did not suffer
      simple sensory impairment. They were selectively impaired in spatial memory when
      the task required the integration of multimodal or olfactory cues. These results,
      in part, resemble some of the reported olfactory discrimination and cognitive
      impairment in schizophrenia.

PMID- 17459717
TI  - Hypoglycemic seizures during transient hypoglycemia exacerbate hippocampal
      dysfunction.
AB  - Severe hypoglycemia constitutes a medical emergency, involving seizures, coma and
      death. We hypothesized that seizures, during limited substrate availability,
      aggravate hypoglycemia-induced brain damage. Using immature isolated, intact
      hippocampi and frontal neocortical blocks subjected to low glucose perfusion, we
      characterized hypoglycemic (neuroglycopenic) seizures in vitro during transient
      hypoglycemia and their effects on synaptic transmission and glycogen content.
      Hippocampal hypoglycemic seizures were always followed by an irreversible
      reduction (>60% loss) in synaptic transmission and were occasionally accompanied
      by spreading depression-like events. Hypoglycemic seizures occurred more
      frequently with decreasing "hypoglycemic" extracellular glucose concentrations.
      In contrast, no hypoglycemic seizures were generated in the neocortex during
      transient hypoglycemia, and the reduction of synaptic transmission was reversible
      (<60% loss). Hypoglycemic seizures in the hippocampus were abolished by NMDA and
      non-NMDA antagonists. The anticonvulsant, midazolam, but neither phenytoin nor
      valproate, also abolished hypoglycemic seizures. Non-glycolytic, oxidative
      substrates attenuated, but did not abolish, hypoglycemic seizure activity and
      were unable to support synaptic transmission, even in the presence of the
      adenosine (A1) antagonist, DPCPX. Complete prevention of hypoglycemic seizures
      always led to the maintenance of synaptic transmission. A quantitative glycogen
      assay demonstrated that hypoglycemic seizures, in vitro, during hypoglycemia
      deplete hippocampal glycogen. These data suggest that suppressing seizures during
      hypoglycemia may decrease subsequent neuronal damage and dysfunction.

PMID- 17459718
TI  - Patient selection for minimally invasive aortic valve implantation.

PMID- 17459720
TI  - TGFbeta regulates the expression and activities of G2 checkpoint kinases in human
      myeloid leukemia cells.
AB  - Transforming Growth Factor-beta (TGFbeta) is known to be a negative regulator of
      G1 cyclin/cdk activity. It is not clear whether TGFbeta has any effect on G2
      checkpoint kinases. We have found that TGFbeta downregulated the expression of
      several G2 checkpoint kinases including cdc2, cyclin B1, and cdc25c without
      causing cell accumulation in G2/M phases in two human leukemia cell lines. The
      inhibition was time-dependent with a maximal inhibition being observed by 24h for
      cyclin B1 and cdc2 and by 48h for cdc25c. The inhibition was not a result of G1
      arrest but a direct effect of TGFbeta which downregulates their expression at
      mRNA level. In proliferating cells, there was a significant formation of cdc2-pRb
      complexes, which was decreased to 30% of control levels by 48h after initiating
      TGFbeta treatment. Cdc2 showed a marked kinase activity on GST-Rb protein in
      proliferating cells detected by in vitro kinase assay, which was downregulated in
      response to TGFbeta. In addition, TGFbeta caused a rapid and transient
      dephosphorylation of cdc2 (Tyr15) and cdc25c (Ser216) for about 2-3h before a
      dramatic decrease of both molecules by 48h. Taken together, our data suggest that
      TGFbeta has a direct inhibitory effect on G2 checkpoint kinases, which is
      regulated at mRNA level. The transient activation of cdc2 and cdc25c and
      subsequent inhibition of cdc2, cyclin B1, and cdc25c could amplify TGFbeta
      induced G1 arrest and growth inhibition.

PMID- 17459721
TI  - Ligand binding mode to duplex and triplex DNA assessed by combining electrospray
      tandem mass spectrometry and molecular modeling.
AB  - In this paper, we report the analysis of seven benzopyridoindole and
      benzopyridoquinoxaline drugs binding to different duplex DNA and triple helical
      DNA, using an approach combining electrospray ionization mass spectrometry (ESI
      MS), tandem mass spectrometry (MS/MS), and molecular modeling. The ligands were
      ranked according to the collision energy (CE(50)) necessary to dissociate 50% of
      the complex with the duplex or the triplex in tandem MS. To determine the
      probable ligand binding site and binding mode, molecular modeling was used to
      calculate relative ligand binding energies in different binding sites and binding
      modes. For duplex DNA binding, the ligand-DNA interaction energies are roughly
      correlated with the experimental CE(50), with the two benzopyridoindole ligands
      more tightly bound than the benzopyridoquinoxaline ligands. There is, however, no
      marked AT versus GC base preference in binding, as supported both by the ESI-MS
      and the calculated ligand binding energies. Product ion spectra of the complexes
      with triplex DNA show only loss of neutral ligand for the
      benzopyridoquinoxalines, and loss of the third strand for the benzopyridoindoles,
      the ligand remaining on the duplex part. This indicates a higher binding energy
      of the benzopyridoindoles, and also shows that the ligands interact with the
      triplex via the duplex. The ranking of the ligand interaction energies compared
      with the CE(50) values obtained by MS/MS on the complexes with the triplex
      clearly indicates that the ligands intercalate via the minor groove of the Watson
      Crick duplex. Regarding triplex versus duplex selectivity, our experiments have
      demonstrated that the most selective drugs for triplex share the same
      heteroaromatic core.

PMID- 17459722
TI  - Neuronal nitric oxide synthase (NOS-I) knockout increases the survival rate of
      neural cells in the hippocampus independently of BDNF.
AB  - Investigations regarding the regulation of adult neurogenesis, i.e., the
      generation of new neurons from progenitor cells, have revealed a high degree of
      complexity. Although the pleiotropic messenger molecule nitric oxide (NO) has
      been suggested to modulate adult neurogenesis, the evidence is inconclusive due
      to the presence of different NO synthase isoforms in the brain. We therefore
      investigated whether stem cell proliferation or survival is altered in mice
      lacking neuronal nitric oxide synthase (NOS-I) or both endothelial and neuronal
      NOS (NOS-I/-III double knockout). While proliferation of neural stem cells was
      only numerically, but not significantly increased in NOS-I knockdown animals, the
      survival of newly formed neurons was substantially higher in NOS-I-deficient
      mice. In contrast, NOS-I/-III double knockout had significantly decreased
      survival rates. QRT-PCR in NOS-I-deficient mice revealed neither NOS-III
      upregulation compensating for the loss of NOS-I, nor alterations in VEGF levels
      as found in NOS-III-deficient animals. As changes in BDNF expression or protein
      levels were observed in the cortex, cerebellum and striatum, but not the
      hippocampus, the increase in stem cell survival appears not to be due to a BDNF
      mediated mechanism. Finally, NOS-I containing neurons in the dentate gyrus are
      rare and not localized close to progenitor cells, rendering direct NO effects on
      these cells unlikely. In conclusion, we suggest that NO predominantly inhibits
      the survival of new-born cells, by an indirect mechanism not involving BDNF or
      VEGF. Together, these results emphasize the important role of the different NOS
      isoforms with respect to adult neurogenesis.

PMID- 17459723
TI  - Over-expression and refolding of MAP kinase phosphatase 3.
AB  - MAP kinase phosphatase 3 (MKP3, also known as DUSP6 and PYST1) is involved in
      extracellular signal receptor kinase (ERK) regulation and functions as a specific
      phosphatase to the activated (phosphorylated) forms of ERK1 and ERK2. MKP3
      displays allosteric activation, which aids in tightly regulating its function to
      ERK substrates, but not other related MAPKs. Due to MKP3's specificity for the
      ERK signaling pathway, the development of specific activators or inhibitors to
      the enzyme have been suggested in order to expressly influence the ERK1 and ERK2
      pathways. To produce the high yields of MKP3 protein necessary for physico
      chemical characterization of MKP3 and for high throughput screening of its small
      molecule activators and inhibitors, we have cloned, purified and, and identified
      refolding conditions suitable for producing full-length, human MKP3 from
      Escherichia coli inclusion bodies. Furthermore, we demonstrate the use of a 96
      well plate format refolding assay in which the ERK-induced activity of MKP3 is
      simulated by 33% DMSO. The assay allowed for rapid detection of MKP3's function
      following a refolding screen in the absence of ERK and thus provides quick and
      inexpensive testing of MKP3 activity. Following screening, the refolded product
      was confirmed to be correctly folded by steady-state kinetic analysis and by the
      CD spectroscopy-determined secondary structure content. CD data were consistent
      with 36% helix and 14% sheet, which compared to an expected 32.9% helix and 12.4%
      sheet. These data indicated that MKP3 was properly folded, making it a suitable
      protein for use in functional studies.

PMID- 17459724
TI  - Overexpression and functional analysis of cold-active beta-galactosidase from
      Arthrobacter psychrolactophilus strain F2.
AB  - Cold-active beta-galactosidase from Arthrobacter psychrolactophilus strain F2 was
      overexpressed in Escherichia coli using the Cold expression system and the
      recombinant enzyme, rBglAp, was characterized. The purified rBglAp exhibited
      similar enzymatic properties to the native enzyme, e.g., (i) it had high activity
      at 0 degrees C, (ii) its optimum temperature and pH were 10 degrees C and 8.0,
      respectively, and (iii) it was possible to rapidly inactivate the rBglAp at 50
      degrees C in 5 min. Moreover, rBglAp was able to hydrolyze both ONPG and lactose
      with K(m) values of 2.7 and 42.1mM, respectively, at 10 degrees C. One U of
      rBglAp could hydrolyze about 70% of the lactose in 1 ml of milk in 24h, and the
      enzyme produced trisaccharide from lactose. We conclude that rBglAp is a cold
      active enzyme that is extremely heat labile and has significant potential
      application to the food industry.

PMID- 17459725
TI  - Affinity chromatography of native SUMO proteins using His-tagged recombinant UBC9
      bound to Co2+-charged talon resin.
AB  - Four small ubiquitin-related modifier (SUMO) genes have been identified in
      humans. The recently identified SUMO4 was detected in mRNA transcripts from
      HEK293 cells, and human kidney and spleen tissue and may be involved in
      regulation of NF-kappaB and susceptibility to autoimmune diseases. However,
      identification and characterization of a native SUMO4 protein has not yet been
      reported. Here, we analyzed for the presence of native SUMO proteins in HEK293
      cells and human kidney tissue using an affinity purification procedure using a
      UBC9 matrix followed by mass spectroscopy analyses for SUMO-specific peptides.
      Identification by mass spectroscopy of peptides generated by Trypsin and Lys-C
      digestion did reveal peptides unique to SUMO1 and SUMO2/3, but not SUMO4. In
      control experiments, SUMO4 prepared by recombinant methods was isolated and even
      enriched by our UBC9 affinity purification. Thus, SUMO4 protein appears to be
      either in extremely low abundance in human kidney or HEK293 cells or it is not
      present at all. It remains possible that SUMO4 protein is more abundant in other
      cell types or can be induced by hormonal or environmental challenges and the
      procedures reported here should be extremely useful for detecting native SUMO4.
      Furthermore, using His-tagged recombinant proteins bound to Co(2+)-charged Talon
      resin has general applicability to isolate native proteins that have strong non
      covalent interactions with the resin-bound His-tagged proteins.

PMID- 17459726
TI  - Health status, health conditions, and health behaviors among Amish women. Results
      from the Central Pennsylvania Women's Health Study (CePAWHS).
AB  - We performed one of the first systematic, population-based surveys of women in
      Amish culture. We used these data to examine health status and health risks in a
      representative sample of 288 Amish women ages 18-45 living in Lancaster County,
      Pennsylvania, in particular for risks associated with preterm and low birthweight
      infants, compared with a general population sample of 2,002 women in Central
      Pennsylvania. Compared with women in the general population, Amish women rated
      their physical health approximately at the same level, but reported less stress,
      fewer symptoms of depression, and had higher aggregate scores for mental health.
      Amish women reported low levels of intimate partner violence, high levels of
      social support, and they perceived low levels of unfair treatment owing to gender
      compared with the general population. Amish women also reported higher fertility,
      fewer low birthweight babies, but the same number of preterm births as the
      general population. The findings suggest that these outcomes may be due to higher
      levels of social support and better preconceptional behavior among Amish women.

PMID- 17459727
TI  - CpG oligodeoxynucleotides up-regulate antibacterial systems and induce protection
      against bacterial challenge in rainbow trout (Oncorhynchus mykiss).
AB  - The effects of unmethylated CpG oligodeoxynucleotides (ODN) on the mammalian
      immune system are relatively well studied but much less is known of their effects
      on the immune systems of different fish species. Here we show that CpG ODNs
      significantly enhance the survival of rainbow trout (Oncorhynchus mykiss)
      following bacterial challenge when used both as stand-alone prophylactic agents,
      or as adjuvants to a commercially available vaccine. They are also capable of
      increasing serum lysozyme activity in vivo and stimulating the production of
      chemoattractant factors for rainbow trout head kidney (HK) leucocytes in vitro.

PMID- 17459728
TI  - Firing rate and conduction velocity of single motor units in the trapezius muscle
      in fibromyalgia patients and healthy controls.
AB  - Fibromyalgia is a common chronic pain condition in the population (2-4%), which
      often is associated with prominent negative consequences with respect to
      participation in daily activities. There are several reports in the literature
      concerning the effects of acute experimental pain on motor control. However, a
      more heterogeneous picture exists in the literature with respect to whether
      chronic pain conditions affect motor control. This study compares firing rate and
      conduction velocity (CV) of single motor units (MUs) in the trapezius muscle of
      fibromyalgia patients (FM) and healthy controls (CON). Multi-channel surface
      electromyography was used to estimate both MU firing rate and CV because this
      technique allows simultaneous estimation of both these variables and the
      measurements are easy and non-invasive. In this study, 29 FM and 30 CON subjects
      participated and performed isometric shoulder elevations using weights up to 4
      kg. No significant differences in the firing rate of MUs in the trapezius muscle
      were found between the FM and CON groups (95% confidence interval was -1.9 and
      1.3 pulses per second). There were no significant differences in CV between the
      groups at 1 and 2 kg load. However, the FM group had significantly higher CV in
      contractions without external load (p=0.004). We were unable to confirm the pain
      adaptation model since no differences in firing rate between the two groups were
      found. CV was significantly higher in FM than in healthy controls; this might be
      due to alterations in histopathology and microcirculation.

PMID- 17459729
TI  - The morphology of the medial gastrocnemius in typically developing children and
      children with spastic hemiplegic cerebral palsy.
AB  - We collected 3D ultrasound images of the medial gastrocnemius muscle belly (MG)
      in 16 children with spastic hemiplegic cerebral palsy (SHCP) (mean age: 7.8
      years; range: 4-12) and 15 typically-developing (TD) children (mean age: 9.5
      years; range: 4-13). All children with SHCP had limited passive dorsiflexion
      range on the affected side with the knee extended (mean+/-1SD: -9.3 degrees +/
      11.8). Scans were taken of both legs with the ankle joint at its resting angle
      (RA) and at maximum passive dorsiflexion (MD), with the knee extended. RA and MD
      were more plantar flexed (p<0.05) in children with SHCP than in TD children. We
      measured the volumes and lengths of the MG bellies. We also measured the length
      of muscle fascicles in the mid-portion of the muscle belly and the angle that the
      fascicles made with the deep aponeurosis of the muscle. Volumes were normalised
      to the subject's body mass; muscle lengths and fascicle lengths were normalised
      to the length of the fibula. Normalised MG belly lengths in the paretic limb were
      shorter than the non-paretic side at MD (p=0.0001) and RA (p=0.0236). Normalised
      muscle lengths of the paretic limb were shorter than those in TD children at both
      angles (p=0.0004; p=0.0003). However, normalised fascicle lengths in the non
      paretic and paretic limbs were similar to those measured in TD children (p>0.05).
      When compared to the non-paretic limb, muscle volume was reduced in the paretic
      limb (p<0.0001), by an average of 28%, and normalised muscle volume in the
      paretic limb was smaller than in the TD group (p<0.0001). The MG is short and
      small in the paretic limb of children with SHCP. The altered morphology is not
      due to a decrease in fascicle length. We suggest that MG deformity in SHCP is
      caused by lack of cross-sectional growth.

PMID- 17459730
TI  - Cortical thickness in single- versus multiple-domain amnestic mild cognitive
      impairment.
AB  - Amnestic mild cognitive impairment (aMCI) can be classified into single domain (S
      aMCI) and multiple domain (M-aMCI) subtypes. However, there have been no studies
      that specifically investigate the structural differences that support this
      classification. In an attempt to compare regional cortical thickness in two
      subtypes of aMCI, we aimed to map the distribution of cortical thinning using a
      surface based cortical analysis of magnetic resonance imaging. The cortical
      thickness across the entire brain was measured in 9 patients with S-aMCI, 22
      patients with M-aMCI, and 61 normal healthy subjects. Differences in the patterns
      of cortical thinning between S-aMCI and M-aMCI were assessed using ANCOVA on a
      vertex-by-vertex basis, and statistical maps of differences in cortical thickness
      between the groups were constructed using a surface model. Relative to controls,
      S-aMCI patients showed cortical thinning in the left medial temporal lobe, and M
      aMCI patients showed cortical thinning in the left medial temporal lobe,
      precuneus, and anterior and inferior basal temporal, insular, and temporal
      association cortices. When the two MCI groups were directly compared, M-aMCI
      patients showed cortical thinning in left precuneus. Our studies suggest that M
      aMCI is a transitional state between S-aMCI and Alzheimer's disease, and that the
      cortical thinning is evidence that the precuneus is responsible for the multiple
      cognitive impairments in M-aMCI.

PMID- 17459731
TI  - Cerebellar activation during discrete and not continuous timed movements: an fMRI
      study.
AB  - Individuals with cerebellar lesions are impaired in the timing of repetitive
      movements that involve the concatenation of discrete events such as tapping a
      finger. In contrast, these individuals perform comparably to controls when
      producing continuous repetitive movements. Based on this, we have proposed that
      the cerebellum plays a key role in event timing-the representation of the
      temporal relationship between salient events related to the movement (e.g.,
      flexion onset or contact with a response surface). In the current study, we used
      fMRI to examine cerebellar activity during discrete and continuous rhythmic
      movements. Participants produced rhythmic movements with the index finger either
      making smooth, continuous transitions between flexion and extension or with a
      pause inserted before each flexion phase making the movement discrete. Lateral
      regions in lobule VI, ipsilateral to the moving hand were activated in a similar
      manner for both conditions. However, activation in the superior vermis was
      significantly greater when the movements were discrete compared to when the
      movements were continuous. This pattern was not evident in cortical regions
      within the field of view, including M1 and SMA. The results are consistent with
      the hypothesis that subregions of the cerebellum are selectively engaged during
      tasks involving event timing.

PMID- 17459732
TI  - Pro-proliferating effect of homologous somatic cells on chicken primordial germ
      cells.
AB  - Many studies demonstrated that chicken primordial germ cells (PGCs) could
      maintain undifferentiated state on mouse embryonic fibroblast feeders
      supplemented with growth factors and cytokines. However, the xenosupport systems
      may run risk of cross-transfer of animal pathogens from the other animal feeder,
      matrix to the PGCs, then influencing later transgenic technology. In this study,
      chicken PGCs were identified by alkaline phosphatase, stage-specific embryonic
      antigen-1 and Oct-4 immunocytochemical stainings. Three different homologous
      somatic cell feeder layers (chicken embryonic fibroblast feeder layer, CEF;
      embryonic skeletal myoblast feeder layer; follicular granulosa cell feeder layer)
      were used to support growth and proliferation of PGCs to find a better supporting
      culture system. In addition, the effects of fetal calf serum (FCS), leukemia
      inhibitory factor (LIF) and the combination of insulin, transferring and selenite
      (ITS) on PGC proliferation were compared. Results showed that CEF was the best
      supporter for PGC growth and proliferation, which was verified by 5-bromo-2'
      deoxyuridine incorporation stain. FCS alone or in combination with LIF could
      significantly promote PGC proliferation in the presence of CEF in ITS medium.
      This study will contribute to providing a safer supporting system for chicken PGC
      amplification in vitro, and may be applied in transgenic chicken production and
      transplantation therapy.

PMID- 17459733
TI  - The low rate of HLA class I molecules on the human embryonic stem cell line HS293
      is associated with the APM components' expression level.
AB  - Human embryonic stem cells (hESCs) represent a promise for future strategies of
      tissue replacement. However, there are different issues that should be resolved
      before these cells can be used in cellular therapies; among others, the rejection
      of transplantable hESCs as a result of HLA incompatibility between donor cells
      and recipients. The hESCs exhibit a weak HLA class I expression on the cell
      surface, but today the responsible mechanisms are unknown. We have analyzed the
      level expression of HLA class I heavy chain, beta2-microglobulin (beta2-m), and
      antigen-processing machinery (APM) components (TAP1, TAP2, LMP2, LMP7, and
      Tapasin) using the HS293 hESC line by real-time quantitative RT-PCR. This
      analysis has revealed a low expression of beta2-m, HLA-B, and Tapasin, and an
      absence of expression of: TAP1, TAP2, LMP2, and LMP7 genes in the HS293 hESC line
      respect to the embryoid bodies (EBs) and the induced stem cells with IFNgamma
      (with significant differences, p<0.05). The lack or loss of HLA class I molecules
      due to the down-regulation of the APM components has been frequently found in
      tumors of different histology as specific mechanisms of immune-evasion. We
      described for the first time in this report that the hESCs shared similar
      mechanisms with respect to tumor cells responsible for the weak HLA class I
      expression on the cell surface.

PMID- 17459734
TI  - A developmental dissociation in reinstatement of an extinguished fear response in
      rats.
AB  - Recently, studies from our laboratory have shown that 16-day-old rats, in
      contrast to 23-day-old rats, fail to show either ABA renewal or recovery of an
      extinguished fear response following a pre-test injection of FG7142 [Kim, J. H. &
      Richardson, R. (2007). A developmental dissociation of context and GABA effects
      on extinguished fear in rats. Behavioral Neuroscience; Yap & Richardson,
      unpublished data]. The present study, using freezing as a measure of learned
      fear, extends these findings by examining whether there is a developmental
      difference in susceptibility to reinstatement following extinction. 16- and 23
      day-old rats were trained to fear a white-noise conditioned stimulus (CS) by
      pairing it with a shock unconditioned stimulus (US). This fear was subsequently
      extinguished by non-reinforced presentations of the CS. Some rats received a post
      extinction Reminder which consisted of a single presentation of a reduced
      intensity US. Experiments 1 and 2 demonstrated that this Reminder was effective
      in reinstating extinguished fear in 23-day-olds, and that this reinstatement
      effect was context-specific in rats this age. In contrast, 16-day-old rats failed
      to show the reinstatement effect in either experiment. The failure to observe a
      post-extinction reinstatement effect in the 16-day-olds was not due to a general
      ineffectiveness of the Reminder treatment at this age because it did alleviate
      spontaneous forgetting in rats this age (Experiment 3). Taken together, the
      results suggest that fundamentally different processes may mediate extinction
      early in development compared to later in development.

PMID- 17459735
TI  - Extracellular terbium and divalent cation effects on the red blood cell Na pump
      and chrysoidine effects on the renal Na pump.
AB  - We examined the effect of extracellular terbium (Tb(3+)) and divalent metal
      cations (Ca(2+), Sr(2+), and Ba(2+)) on (86)Rb(+) influx into rabbit and human
      red blood cells. We found that Tb(3+) at 15 and 25 microM was a non-competitive
      inhibitor of (86)Rb(+) influx suggesting that Tb(3+) is not binding to the
      transport site. This result reduces the usefulness of Tb(3+) as a potential probe
      for the E(out) conformation (the conformation with the transport site facing
      extracellularly). Ba(2+), Sr(2+) and Ca(2+), at concentrations >50 mM, had
      minimal effects on Rb(+) influx into red blood cells (1 mM Rb-out). This suggests
      that the outside transport site is very specific for monovalent cations over
      divalent cations, in contrast to the inside transport site. We also found that
      chrysoidine (4-phenylazo-m-phenylenediamine) competes with Na(+) for ATPase
      activity and K(+) for pNPPase activity suggesting it is binding to the E(in)
      conformation. Chrysoidine and similar compounds may be useful as optical probes
      of the E(in) conformation.

PMID- 17459736
TI  - The nuclear nurture and cytoplasmic nature of localized mRNPs.
AB  - From yeast to mammals, evidence has emerged in recent years highlighting the
      essential role played by the nuclear "history" of a messenger RNA in determining
      its cytoplasmic fate. mRNA localization, translation and stability in the
      cytoplasm are often pre-destined in the nucleus, and directed by the composition
      and architecture of nuclear assembled mRNA-protein complexes. In this review we
      focus on nuclear-acquired RNA-binding proteins and complexes that participate in
      determining the journey of localized mRNAs.

PMID- 17459737
TI  - Maintaining nitric oxide-induced airway relaxation with superoxide dismutase.
AB  - BACKGROUND: We have previously shown that the protective effect of inhaled nitric
      oxide (iNO) against methacholine-induced bronchoconstriction is negated in
      airways subjected to hyperosmotic stress. In this study, hypothesizing that the
      impaired efficiency of iNO was caused by release of reactive oxygen radicals, we
      examined the effect of the radical scavenging enzyme superoxide dismutase (SOD).
      METHODS: Hemodynamic and respiratory measurements were performed on anesthetized
      rabbits after (1) inhalation of methacholine (MCh), (2) iNO (80ppm), followed by
      MCh, (3) inhalation of hypertonic saline (HS), followed by iNO and MCh and (4)
      pre-treatment with inhalation of SOD, followed by HS, iNO and MCh. We analyzed
      plasma for a marker of oxidative stress, 8-iso-prostaglandin (PG)F(2alpha) and
      for a marker of activation of COX-mediated inflammatory cascades, PGF(2alpha)
      metabolite. RESULTS: Pre-treatment with SOD restored the bronchoprotective
      response to iNO in hyperosmotic airways. No direct effect was seen by SOD
      treatment on levels of 8-iso-PGF(2alpha), but this marker of oxidative stress
      correlated positively with increased bronchoconstriction. Hyperosmotic challenge
      elevated levels of PGF(2alpha) metabolite, and pre-treatment with SOD protected
      against this activation of the inflammatory cascade. CONCLUSION: SOD pre
      treatment restores the relaxant effects of iNO in hyperosmotically challenged
      airways by attenuating oxidative stress and activation of COX-mediated
      inflammatory cascades.

PMID- 17459738
TI  - Complex carcinomas of the mammary gland in cats: pathological and
      immunohistochemical features.
AB  - Biphasic epithelial myoepithelial (complex) carcinomas of the feline mammary
      gland are rare. This article describes the pathological and immunohistochemical
      features and clinical outcome of eight cases of feline mammary carcinomas
      displaying complex morphology. This tumour type is a low grade malignancy that
      shows histopathological features distinctive from more common feline mammary
      carcinomas and from complex mammary carcinomas of dogs. It appears to have a
      better overall survival than other carcinomas of the mammary gland of cats.

PMID- 17459739
TI  - CINRG pilot trial of oxatomide in steroid-naive Duchenne muscular dystrophy.
AB  - The authors report a pilot open-label two-center therapeutic trial of oxatomide
      in 14 steroid-naive DMD boys aged 5-10 years. Comparison of linear evolutions
      between 3 months medication-free lead-in periods and 6 months treatment periods
      showed no significant differences in quantitative (QMT) and manual (MMT)
      measurements of muscle strength and timed functional tests. A modest mitigation
      of strength deterioration over time cannot be excluded.

PMID- 17459741
TI  - A randomised controlled study of reflexology for the management of chronic low
      back pain.
AB  - The use of complementary and alternative medicine (CAM) for the management of
      chronic low back pain (CLBP) continues to rise. However, questions regarding the
      efficacy of many CAM therapies for CLBP remain unresolved. The present study
      investigated the effectiveness of reflexology for CLBP. A pragmatic randomised
      controlled trial was conducted. N=243 patients were randomised to one of three
      groups: reflexology, relaxation, or non-intervention (usual care). All completed
      a questionnaire booklet before and after the treatment phase, and at six months
      follow up. This measured their general health status, pain, functioning, coping
      strategies and mood. After adjusting for pre-treatment scores repeated measures
      ANCOVA found no significant differences between the groups pre and post treatment
      on the primary outcome measures of pain and functioning. There was a main effect
      of pain reduction, irrespective of group. Trends in the data illustrated the pain
      reduction was greatest in the reflexology group. Thus, the current study does not
      indicate that adding reflexology to usual GP care for the management of CLBP is
      any more effective than usual GP care alone.

PMID- 17459742
TI  - Biochemical alterations in the trapezius muscle of patients with chronic whiplash
      associated disorders (WAD)--a microdialysis study.
AB  - The mechanisms behind the development of chronic trapezius myalgia in patients
      with whiplash associated disorders (WAD) appear to involve both peripheral and
      central components, but the specific contribution of alterations in muscle is not
      clear. Female patients with WAD and involvement of trapezius (N=22) and female
      controls (N=20; CON) were studied during an experiment compromised of rest
      (baseline), 20min repetitive low-force exercise and 120min recovery. Their
      interstitial concentrations of serotonin (5-HT), glutamate, lactate, pyruvate,
      potassium, interleukin-6 (IL-6), and blood flow were determined in the trapezius
      muscle using a microdialysis technique. Pressure pain thresholds (PPT) over
      trapezius and tibialis anterior muscles were also assessed. In WAD, we found
      signs of generalized hypersensitivity according to PPT. The WAD group had
      significantly higher interstitial [IL-6] and [5-HT] in the trapezius than the
      CON. [Pyruvate] was overall significantly lower in WAD, and with lactate it
      showed another time-pattern throughout the test. In the multivariate regression
      analysis of pain intensity [5-HT] was the strongest regressor and positively
      correlated with pain intensity in WAD. In addition, blood flow, [pyruvate], and
      [potassium] influenced the pain intensity in a complex time dependent way. These
      findings may indicate that peripheral nociceptive processes are activated in WAD
      with generalized hypersensitivity for pressure and they are not identical with
      those reported in chronic work-related trapezius myalgia, which could indicate
      different pain mechanisms.

PMID- 17459744
TI  - Interpreting electron-nuclear-magnetic field interactions from a hamiltonian
      expressed in tensorial notation.
AB  - The general experimental hamiltonian expressed in tensorial notation is assessed
      in a way to ensure that the outcomes from such a hamiltonian reflect correctly
      the electron-nuclear-magnetic field interactions and yields the appropriate
      parameters. Without such knowledge the use of hamiltonians in tensorial notation
      to analyse magnetic resonance spectra may lead to questionable or even
      meaningless results reflected in several publications over the years.
      Furthermore, the errors that may occur in handling mixed hamiltonians compound
      the problem.

PMID- 17459743
TI  - Neuregulin 1 is a pronociceptive cytokine that is regulated by progesterone in
      the spinal cord: implications for sex specific pain modulation.
AB  - Sex differences in the magnitude of response to thermal and tactile stimuli have
      been demonstrated in both clinical and animal studies. Females typically display
      lower threshold responses to painful stimuli as compared to males. We have
      previously observed sexually dimorphic expression of the growth factor,
      neuregulin 1 (NRG1) following L5 nerve root ligation (LR) in male and female
      rats. In the present study, we sought to determine which gonadal hormones were
      involved in regulating NRG1 expression following L5 nerve root ligation. We
      observed that expression of NRG1 mRNA and the neuregulin receptors, ErbB2 and
      ErbB4 in the lumbar spinal cord was facilitated by the presence of progesterone
      in female rats following L5 nerve root ligation. An increase in NRG1 protein and
      NRG1 immunoreactivity was also observed in the ipsilateral spinal cord of
      progesterone treated female rats as compared to ovariectomized female rats and
      male rats at day 14 following LR. NRG1 immunoreactivity was equally colocalized
      with either the astrocytic marker, GFAP, and with NeuN labeled neurons 14days
      following L5 nerve root ligation. Intrathecal administration of recombinant NRG1
      beta1 protein significantly decreased the hindpaw tactile withdrawal threshold in
      male rats, ovariectomized female rats, and progesterone treated female rats.
      These results demonstrate a role for progesterone-dependent regulation of glial
      and/or neuronal neuregulin 1 in female rats in mediating sex differences in
      nociception. Furthermore, our results suggest that NRG1 may be involved in
      central sensitization during the maintenance phase, but not in the initiation of
      persistent pain in female rats.

PMID- 17459745
TI  - Cortical visual impairment: etiology, associated findings, and prognosis in a
      tertiary care setting.
AB  - PURPOSE: To evaluate the etiology, prognosis, and associated neurological and
      ophthalmologic findings of children with cortical visual impairment (CVI) at a
      tertiary care referral facility. METHODS: Records from patients visiting the
      Vanderbilt University Pediatric Ophthalmology Center during 2002 to 2005 were
      reviewed, and 98 patients were identified with an International Classification of
      Disease (9th ed.) coding of CVI (377.75). The charts were reviewed to assess
      presenting symptoms. The clinic and imaging notes were correlated with visual
      function (graded on a scale of I to VI). RESULTS: The most common etiologies were
      perinatal hypoxia (35%), prematurity (29%), hydrocephalus (19%), structural
      central nervous system abnormalities (11%), and seizures (10%). Many children
      (69%) had multiple etiologies. Associated ophthalmic abnormalities included
      esotropia (19%), exotropia (40%), nystagmus (21%), and optic atrophy (42%).
      Significant refractive error (> +3.00 D or < -2.00 D) was common (20%).
      Associated neurological findings included seizures (60%), cerebral palsy (37%),
      periventricular leukomalacia (12%), hemiparesis (21%), and hearing loss (11%).
      Fifty-three percent of children initially diagnosed with CVI were followed for a
      period of 0.5 to 10 years. Forty percent of the patients showed no improvement in
      visual function; 34% had minimal improvement, and 17% had mild improvement. Only
      6% of the patients had significant improvement in visual function. Eight patients
      had fixing and following or better acuity at last follow-up. CONCLUSIONS: The
      major risk factors for CVI are perinatal hypoxia, premature birth, and
      hydrocephalus. Most patients have associated serious neurological and
      ophthalmologic abnormalities. While many patients have some recovery in vision
      acuity, most never see well. Patients with the most improvement in visual
      function were those having better initial acuity.

PMID- 17459746
TI  - Drug design: new inhibitors for HIV-1 protease based on Nelfinavir as lead.
AB  - Nelfinavir (Viracept) is a potent, non-peptidic inhibitor of HIV-1 Protease,
      which has been marketed for the treatment of HIV infected patients. However, HIV
      1 develops drug-resistance which decreases the affinity of Nelfinavir for the
      binding pocket of Protease. We present here three new variants of Nelfinavir,
      which we have designed with computational tools, with greater affinity for HIV-1
      Protease than Nelfinavir itself. Accordingly, we have introduced rational
      modifications in Nelfinavir, optimizing its affinity to the most conserved amino
      acids in Protease, in order to increase the efficiency of the three new
      inhibitors. Minimization and molecular dynamics simulations have been carried out
      on four complexes, HIV-1 Protease with Nelfinavir and subsequently with the new
      inhibitors, respectively, in order to analyze the behavior of the systems.
      Additionally, we have calculated the binding free energy differences
      Protease:inhibitor, which gave us a quantitative idea of the new molecules
      inhibitory efficiency in silico.

PMID- 17459747
TI  - Conservation of closed loops.
AB  - The closed loop hypothesis of Berezovsky and Trifonov implicates the closure of
      loops of length 25-35 through hydrophobic interactions at the 'locks' as a key
      event in protein folding. The hypothesis is supported by published analyses of
      nine major superfolds. Here, we have generated multiple sequence alignments for
      the nine superfolds with PDB codes lthb, 1ilb, 256b, 2rhe, 1aps, 2stv, 4fxn
      (2fox), lubq and 7tim and have analysed the degree of conservation at the loop
      ends. Seventy percent of these loop ends are found to be well conserved and the
      peak in the distribution of distances between these well conserved regions lies
      at around 25 residues; both observations are consistent with the Berezovsky and
      Trifonov's hypothesis.

PMID- 17459748
TI  - Validation of a novel risk estimation tool for predicting low bone density in
      Caucasian and African American men veterans.
AB  - Osteoporosis in men is a frequently missed diagnosis. We developed an additive
      risk index, Mscore (male, "simple calculated osteoporosis risk estimation"),
      based on bone mineral density (BMD) at the femoral neck (FN) in 639 ambulatory
      older male veterans. Mscore was derived from the nearest whole number ratio among
      regression coefficients for 5 variables independently associated with
      osteoporosis. Mscore=[2 x (patient age in decades)-(weight in lb/10)+4 if
      gastrectomy, +4 if emphysema, +3 if two or more prior fractures+14]. Age and
      weight variable scores are truncated to integers (i.e., 7 if 75 yr, 18 if 185
      lb). Increased risk is reflected in higher Mscore values. We validated Mscore in
      197 Caucasian male patients (mean age, 69 yr): values of 9 or higher had 88%
      sensitivity, 57% specificity, and an area under the curve (AUC) of 0.84 for
      predicting osteoporosis at the FN (population prevalence, 11%). Mscore values
      ranged from -9 to 20 allowing us to define low (<9), moderate (9-13), or high
      (>13) risk categories. Two percent of low-risk men had osteoporosis, 36% or 55%
      of high-risk men had osteoporosis or osteopenia, respectively. In younger African
      American (n=134) male veterans (mean age, 61 yr), age and weight were the only
      variables independently predictive of FN BMD. A reduced Mscore(age-weight) (age
      and weight variable scores+14) at a cutoff threshold of 9 predicted osteoporosis
      in African American men (population prevalence, 3%) with a sensitivity of 100%, a
      specificity of 73%, and an AUC of 0.99. Finally, we compared Mscore with another
      validated osteoporosis self-assessment tool (OST). OST at a cutoff threshold of 4
      or Mscore(age-weight) at a cutoff threshold of 9 performed similarly in both of
      our populations of Caucasian and African American men. In conclusion, a validated
      Mscore index with 5 variables was only slightly more robust for predicting
      osteoporosis in older Caucasian men than 2 (independently derived) risk indices
      based on age and weight. Mscore(age-weight) or OST is easy to use and can be
      applied in populations of younger African American men.

PMID- 17459749
TI  - Respiratory and cardiovascular responses to acute hypoxia and hyperoxia in
      internally pipped chicken embryos.
AB  - During the first day of hatching, the developing chicken embryo internally pips
      the air cell and relies on both the lungs and chorioallantoic membrane (CAM) for
      gas exchange. Our objective in this study was to examine respiratory and
      cardiovascular responses to acute changes in oxygen at the air cell or the rest
      of the egg during internal pipping. We measured lung (VO2(lung)) and CAM
      (VO2(CAM)) oxygen consumption independently before and after 60 min exposure to
      combinations of hypoxia, hyperoxia, and normoxia to the air cell and the
      remaining egg. Significant changes in VO2(total) were only observed with combined
      egg and air cell hypoxia (decreased VO2(total)) or egg hyperoxia and air cell
      hypoxia (increased VO2(total)). In response to the different O2 treatments, a
      change in VO2(lung) was compensated by an inverse change in VO2(CAM) of similar
      magnitude. To test for the underlying mechanism, we focused on ventilation and
      cardiovascular responses during hypoxic and hyperoxic air cell exposure.
      Ventilation frequency and minute ventilation (V(E)) were unaffected by changes in
      air cell O2, but tidal volume (V(T)) increased during hypoxia. Both V(T) and V(E)
      decreased significantly in response to decreased P(CO2). The right-to-left shunt
      of blood away from the lungs increased significantly during hypoxic air cell
      exposure and decreased significantly during hyperoxic exposure. These results
      demonstrate the internally pipped embryo's ability to control the site of gas
      exchange by means of altering blood flow between the lungs and CAM.

PMID- 17459750
TI  - Seasonal variability of free amino acids in two marine bivalves, Macoma balthica
      and Mytilus spp., in relation to environmental and physiological factors.
AB  - The seasonal variability of the intracellular free amino acid (FAA) concentration
      was studied in 5 Macoma balthica populations and 7 Mytilus spp. populations along
      their European distribution. Because of the well known physiological role of FAA
      as organic osmolytes for salinity induced cell volume regulation in marine
      osmoconformers, FAA variations were compared in bivalve populations that were
      exposed to high vs. low intraannual salinity fluctuations. In general, seasonal
      FAA variations were more pronounced in M. balthica than in Mytilus spp. In both
      bivalve taxa from different locations in the Baltic Sea, highest FAA
      concentrations were found in autumn and winter and low FAA concentrations were
      measured in summer. Seasonal patterns were less pronounced in both taxa at
      locations with constant salinity conditions. In contrast to Baltic Sea
      populations, Atlantic and Mediterranean bivalves showed high FAA concentrations
      in summer and low values in winter, regardless of seasonal salinity fluctuations.
      Significant seasonal FAA variations at locations with constant salinity
      conditions showed that salinity appeared not to be the main factor in determining
      FAA concentrations. The seasonal patterns of the main FAA pool components, i.e.
      alanine, glycine and taurine, are discussed in the context of seasonal variations
      in environmental factors (salinity, temperature) and physiological state
      (glycogen content, reproductive stage).

PMID- 17459751
TI  - Preclinical dose ranging studies for enzyme replacement therapy with idursulfase
      in a knock-out mouse model of MPS II.
AB  - Mucopolysaccharidosis II (MPS II; Hunter syndrome) is an X-linked metabolic
      disorder caused by a deficiency of the lysosomal enzyme iduronate-2-sulfatase
      (I2S), which catalyzes the catabolism of glycosaminoglycans (GAG) by cleaving the
      O-linked sulfate from dermatan sulfate and heparan sulfate. Recently, enzyme
      replacement therapy (ERT) with recombinant human I2S (Elaprase (idursulfase),
      Shire Human Genetic Therapies, Inc.), has been approved in the US and European
      Union for the treatment and management of MPS II. The purpose of the studies
      presented here was to describe some of the preclinical development of idursulfase
      using the I2S knock-out mouse model of MPS II designed to study the effect of
      dose and various dosing regimens of idursulfase on urine and tissue GAG levels.
      Urine and tissue samples were collected prior to idursulfase treatment and
      periodically throughout each study and analyzed for GAGs. The presence of anti
      idursulfase antibodies in the mice serum after idursulfase use was also
      determined. Results showed that idursulfase, at several doses and at several
      dosing frequencies, caused a reduction in tissue and urine GAG levels in a dose
      dependent manner. These studies also demonstrated that after IV administration,
      idursulfase is biologically active in the IdS-KO mouse model and is transported
      to key target tissues, reaching the lysosomes in an active form, and degrading
      the accumulated GAG. In conclusion, these results indicated that ERT with
      idursulfase produced in a human cell line could be useful in the treatment and
      management of MPS II, and were used in the design of clinical studies to evaluate
      the efficacy of idursulfase in MPS II patients.

PMID- 17459752
TI  - C-terminal end and aminoacid Lys48 in HMG-CoA lyase are involved in substrate
      binding and enzyme activity.
AB  - 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) lyase adopts a (betaalpha)(8) TIM barrel
      structure with an additional beta9, alpha11 and alpha12 helices. Location of HMG
      part of the substrate has been suggested but the binding mode for the CoA moiety
      remains to be resolved. As mutation F305 fs(-2), which involves the last 21
      residues of the protein, and mutation K48N caused 3-hydroxy-3-methylglutaric
      aciduria in two patients, we examined the role of the C-terminal end and Lys(48)
      in enzyme activity. Expression studies of various C-terminal-end-deleted and K48N
      mutated proteins revealed that residues 311-313 (localized in the loop between
      alpha11 and alpha12 helices) and Lys(48) are essential for enzyme activity. An in
      silico docking model locating HMG-CoA on the surface of the enzyme implicates
      Asn(311) and Lys(313) in substrate binding by establishing multiple polar
      contacts with phosphate and ribose groups of adenosine, and Lys(48) by contacting
      the carboxyl group of the panthotenic acid moiety.

PMID- 17459753
TI  - Bacteremia in patients with febrile neutropenia after chemotherapy at a
      university medical center in Malaysia.
AB  - OBJECTIVES: This study was initiated to determine the local profile of blood
      culture isolates and antibiotic sensitivities in febrile neutropenic patients
      following chemotherapy, and to establish if any modifications to treatment
      guidelines are necessary. DESIGN: A total of 116 episodes of febrile neutropenia
      admitted to the adult hematology ward at a university medical center in Malaysia
      were studied retrospectively from January 2004 to January 2005. RESULTS: The
      study showed 43.1% of febrile neutropenic episodes had established bacteremia.
      Gram-negative bacteria accounted for 60.3% of isolates. Sensitivities of Gram
      negative bacteria to the antibiotics recommended in the Infectious Diseases
      Society of America (IDSA) guidelines were 86.1-97.2%. Coagulase-negative
      staphylococci were the most common Gram-positive organisms isolated (23.3%). The
      majority of these were methicillin-resistant. CONCLUSIONS: Carbapenem
      monotherapy, as recommended in the 2002 IDSA guidelines, is effective treatment
      for the infections most often encountered at our center. Combination therapy with
      an aminoglycoside should be considered when using ceftazidime, cefepime or
      piperacillin-tazobactam, particularly in high-risk patients. Vancomycin should be
      used if a Gram-positive organism is suspected or isolated.

PMID- 17459754
TI  - Erythema nodosum associated with Shigella colitis in a 7-year-old boy.

PMID- 17459755
TI  - [Neoadjuvant chemotherapy followed by radiotherapy adapted to the tumor response
      in the primary germinoma of the central nervous system: experience of the Pitie
      Salpetriere Hospital and review of literature].
AB  - PURPOSE: Retrospective analysis of ten cases of germinoma of the central nervous
      system treated in Pitie-Salpetriere Hospital, Paris. PATIENTS AND METHODS: Ten
      male patients were treated from 1997 to 2005 for histologically verified primary
      seminoma of the central nervous system. The median age was 27 years (range 18-40
      years). Our option for the treatment was the association of 3-4 cycles of
      neoadjuvant chemotherapy (cisplatin and etoposide) to radiotherapy. Five patients
      received a craniospinal radiotherapy of 30 Gy (for one patient 36 Gy) followed by
      a tumoral boost from 20 to 24 Gy. For five patients, irradiated volume was
      limited to the tumour, total dose from 24 to 54 Gy (for three patients the total
      dose was from 24 to 30 Gy). Surgery was used for five patients, but only in one
      case was macroscopic complete. RESULTS: Six patients were in situation of
      complete remission after neoadjuvant chemotherapy. All the patients were in
      situation of complete remission after the irradiation. All the patients were
      alive free of disease with a median follow-up 46 months (range 13-90 months).
      CONCLUSION: In spite of the fact that the intracranial germinal tumours are not
      the subject of a consensual treatment strategy, this retrospective analysis
      pleads in favour of chemotherapy followed by limited dose and volume irradiation.

PMID- 17459756
TI  - [Assisted reproductive techniques in women aged 38 years or more].
AB  - OBJECTIVE: More and more young women are delaying childbearing until the fourth
      decade of life: thus, Assisted Reproductive Techniques centres receive more and
      more requests from ageing women. The aim of the study is to analyse the purpose
      of these requests, the biological and clinical features of these patients and the
      results in our infertility centre. PATIENTS AND METHODS: A retrospective study
      was carried out at the CHU of Saint-Etienne from 01.01.01 to 31.12.04. We
      analysed the social, clinical and biological features of 84 couples when the
      woman's age was equal or superior to 38 years, representing 218 cycles. A
      questionnaire was used to collect social data. RESULTS: Several factors can
      explain the increasing number of ageing women consulting for infertility: extend
      university time and professional career, professional stability, contraception
      and late meeting of the partner, false reassuring information concerning progress
      in ART, second child desire after a late first pregnancy, but also second marital
      unions and child desire in the redefined couple. In our study, above 40 years
      old, the pregnancy (19.4 versus 10.5%) and delivery rates (16.7 versus 5.8%)
      clearly decreased in IUI. Thus, most of the clinicians propose, in first choice,
      an IVF cycle to a 40 year-old woman. The ultrasound measurement of antral
      follicle count can accurately evaluate the prognosis in terms of pregnancy
      (P<0.01) and delivery rate (P=0.03). For patients with unfavourable prognosis,
      oocyte donation, embryo donation, or adoption can be considered. DISCUSSION AND
      CONCLUSION: ART cannot compensate for the natural decrease in pregnancy rates and
      the increase in early miscarriages in ageing women. Therefore, it is essential to
      inform young women of the negative effects of age on their potential fertility.

PMID- 17459757
TI  - [About the French bill (June 2006) concerning the possibility of lifting
      anonymity from gametes donors].

PMID- 17459758
TI  - Postmortem cardiac troponin I and creatine kinase MB levels in the blood and
      pericardial fluid as markers of myocardial damage in medicolegal autopsy.
AB  - The present study investigated cardiac troponin I (cTnI) and creatine kinase MB
      (CK-MB) in the blood and pericardial fluid from medicolegal autopsy cases (n=234,
      within 48h postmortem) with regard to the cause of death. The cTnI and CK-MB
      levels in cardiac, peripheral blood and pericardial fluid generally showed a mild
      and gradual postmortem time-dependent elevation (r=0.231-0.449, P<0.05-0.001).
      However, postmortem elevation of cTnI was larger for specific causes of death
      including acute myocardial infarction (AMI), cerebrovascular diseases (CVD),
      hyperthermia, fatal methamphetamine (MA) abuse and carbon monoxide (CO)
      intoxication and insignificant for recurrent myocardial infarction (RMI), chronic
      congestive heart diseases (CHD) and drowning, while that of CK-MB was greater for
      CO intoxication and insignificant for drowning. Cardiac blood and pericardial
      cTnI levels were relatively high for AMI, RMI, hyperthermia, MA abuse and CO
      intoxication, and was low for drowning. Elevated CK-MB level was observed for
      cardiac blood in asphyxiation and MA abuse cases and for peripheral blood in
      hyperthermia and MA abuse cases. When the cTnI/CK-MB ratio was estimated, it was
      independent of postmortem time, and the ratios for cardiac blood and pericardial
      fluid were significantly higher in cases of AMI, RMI, hyperthermia and CO
      intoxication but lower in cases of drowning. Elevations of cTnI levels in cardiac
      blood and pericardial fluid were related to the morphological severity of
      myocardial damage. These findings suggest that elevated cTnI and CK-MB levels in
      blood and pericardial fluid are related to ischemic, hypoxic and/or cytotoxic
      myocardial damage, which are characteristic of the cause of death, although the
      levels increase after death depending on myocardial damage at the time of death.

PMID- 17459759
TI  - The changes in AgNOR parameters of dorsal raphe nucleus neurons are related to
      suicide.
AB  - Depression has been established as the main cause of suicide and the research has
      concentrated on disturbed central serotonergic system in both disorders. The
      dorsal raphe nucleus (DRN) of brain stem is the main source of serotonergic
      innervation of limbic structures fundamental in the regulation of emotionally
      influenced behavior. The study was carried out on paraffin-embedded brains from
      10 depressive patients, among them 5 suicides and 5 non-suicides and 13 matched
      mentally healthy controls. The karyometric parameters of DRN neurons were
      evaluated by AgNOR (Argyrophilic Nucleolar Organizer) silver staining method. The
      significant effect of suicide on nuclear area and AgNOR-ratio found in the
      cumulative analysis of all DRN subnuclei could be relevant for forensic
      diagnostic. The results suggest DRN neurons hypoactivity specific for suicide.
      Whether observed phenomenon is a "common trait" existing also in other diagnostic
      groups of mental disorders remains an open question.

PMID- 17459760
TI  - Myasthenia gravis: an unrecognized cause of head drop in Parkinson's disease.
AB  - Head drop is characterized by marked anterior flexion of the cervical spine,
      caused by weakness of the neck extensors or by increased tone of the flexor
      muscles. We report a woman with Parkinson's disease and head drop not due to
      cervical dystonia (a common cause of antecollis in parkinsonisms). Clinical,
      radiological, and neurophysiological features together with responsiveness to
      anticholinesterases and plasma exchanges indicated the possibility of a
      concomitant myasthenia gravis.

PMID- 17459761
TI  - Synthesis and dynamic NMR studies of Pt(eta(5)-C(5)Me(5))(CO){C(O)NR(2)}
      complexes.
AB  - The formation of Pt(eta(5)-C(5)Me(5))(CO){C(O)NR(2)} (R=Me, Et) complexes was
      established by spectroscopic analysis. The infrared spectra of these complexes
      showed a sharp absorption due to the presence of coordinated carbonyl group in
      the region 2017-2013cm(-1). The N,N-dialkylcarbamoyl ligands showed a
      characteristic CO stretching absorption in the range 1609-1616cm(-1). The proton
      NMR spectra of these complexes revealed the expected singlet arising from five
      equivalent methyl groups on the cyclopentadienyl ring with satellites due to
      coupling to (195)Pt. The N-methyl and N-ethyl protons exhibited very broad
      resonances due to restricted rotation about the N-C bond at room temperature. On
      cooling to -30 degrees C, the N,N-dimethyl protons for complex Pt(eta(5)
      C(5)Me(5))(CO){C(O)NMe(2)} showed two sharp singlets at delta 2.86 and 3.09ppm as
      expected for the static structure. For the N,N-diethyl derivative, Pt(eta(5)
      C(5)Me(5))(CO){C(O)NEt(2)}, the methyl protons exhibited only a single triplet at
      delta 1.06ppm at -10 degrees C due to coupling with the methylene protons. This
      single resonance arises through accidental overlap as the methylene protons of
      the ethyl groups are inequivalent at this temperature and each exhibited a
      quartet at delta 3.33 and 3.70ppm due to coupling with the methyl protons. The
      singlet resonances for the methyl and ring carbons of the eta(5)-C(5)Me(5) group
      found in (13)C{(1)H} NMR spectra are illustrative of the chemical equivalence of
      all the carbon atoms caused by free rotation of the ring in these complexes. The
      signals attributable to the carbonyl and carbamoyl carbon atom resonances are
      found downfield as two singlets each with a large coupling constant to platinum.
      The platinum coupling constants of the downfield resonances could not be
      identified for Pt(eta(5)-C(5)Me(5))(CO){C(O)NMe(2)} due to presence of
      impurities.

PMID- 17459762
TI  - Observation of vibronically excited thioformaldehyde at 62,000-72,000cm(-1) by
      1+1'+1' resonance enhanced multiphoton ionization spectroscopy.
AB  - Vibronically excited thioformaldehyde (H(2)CS) has been studied by two-color
      1+1'+1' resonance enhanced multiphoton ionization (REMPI) spectroscopy, in which
      the C (1)B(2)0(0)(0) state of H(2)CS was selected as an intermediate state for
      the resonant excitation to high-lying electronic states at 62,000-72,000cm(-1).
      In light of the distinctive selection rules for the 1+1'+1' REMPI and one-photon
      direct absorption transitions excited from the C (1)B(2) and X (1)A(1) states of
      H(2)CS, respectively, we have been able to identify 1 valence state (npi,
      pi*(2)), and 14 Rydberg states (n, 5s), (pi, 4s), (n, 3d(xz)), (n, 3d(yz)), (n,
      5p(z)), (n, 5p(x)), (n, 5p(y)), n,4d(z)2), (n, 4d(xz)), (n, 4d(yz)), (n, 6s),
      (pi, 4p(y)), (n, 6p(z)), and (n, 6p(y)), in this study.

PMID- 17459763
TI  - Molecular basis of selective PPARgamma modulation for the treatment of Type 2
      diabetes.
AB  - Peroxisome proliferator-activated receptors (PPARs) (alpha, beta/delta and gamma)
      are lipid sensors capable of adapting gene expression to integrate various lipid
      signals. As such, PPARs are also very important pharmaceutical targets, and
      specific synthetic ligands exist for the different isotypes and are either
      currently used or hold promises in the treatment of major metabolic disorders. In
      particular, compounds of the class of the thiazolinediones (TZDs) are PPARgamma
      agonists and potent insulin-sensitizers. The specific but still broad expression
      patterns of PPARgamma, as well as its implication in numerous pathways,
      constitutes also a disadvantage regarding drug administration, since this
      potentially increases the chance to generate side-effects through the activation
      of the receptor in tissues or cells not affected by the disease. Actually,
      numerous side effects associated with the administration of TZDs have been
      reported. Today, a new generation of PPARgamma modulators is being actively
      developed to activate the receptor more specifically, in a cell and time
      dependent manner, in order to induce a specific subset of target genes only and
      modulate a restricted number of metabolic pathways. We will discuss here why and
      how the development of such selective PPARgamma modulators is possible, and
      summarize the results obtained with the published molecules.

PMID- 17459764
TI  - n-3 and n-6 polyunsaturated fatty acids induce the expression of COX-2 via
      PPARgamma activation in human keratinocyte HaCaT cells.
AB  - Polyunsaturated fatty acids (PUFA) n-3 inhibit inflammation, in vivo and in vitro
      in keratinocytes. We examined in HaCaT keratinocyte cell line whether
      eicosapentaenoic acid (EPA) a n-3 PUFA, gamma-linoleic acid (GLA) a n-6 PUFA, and
      arachidic acid a saturated fatty acid, modulate expression of cyclooxygenase-2
      (COX-2), an enzyme pivotal to skin inflammation and reparation. We demonstrate
      that only treatment of HaCaT with GLA and EPA or a PPARgamma ligand
      (roziglitazone), induced COX-2 expression (protein and mRNA). Moreover
      stimulation of COX-2 promoter activity was increased by those PUFAs or
      rosiglitazone. The inhibitory effects of GW9662 and T0070907 (PPARgamma
      antagonists), on COX-2 expression and on stimulation of COX-2 promoter activity
      by EPA and GLA suggest that PPARgamma is implicated in COX-2 induction. Finally,
      PLA2 inhibitor methyl arachidonyl fluorophosphonate blocked the PUFA effects on
      COX-2 induction, promoter activity and arachidonic acid mobilization suggesting
      involvement of AA metabolites in PPAR activation. These findings demonstrate that
      n-3 and n-6 PUFA increased PPARgamma activity is necessary for the COX-2
      induction in HaCaT human keratinocyte cells. Given the anti-inflammatory
      properties of EPA, we suggest that induction of COX-2 in keratinocytes may be
      important in the anti-inflammatory and protective mechanism of action of PUFAs n
      3 or n-6.

PMID- 17459765
TI  - Crossing the barrier: evolution and spread of a major class of mosaic pbp2x in
      Streptococcus pneumoniae, S. mitis and S. oralis.
AB  - A paradigm for Streptococcus interspecies gene transfer is represented by the
      mosaic pbp genes encoding the target enzymes for beta-lactam antibiotics, the
      penicillin-binding proteins, in Streptococcus pneumoniae. We investigated a
      collection of oral streptococci from three continents by comprehensive multi
      locus sequence typing analysis in order to trace the origin of a mosaic block
      belonging to a dominant family of mosaic pbp2x implicated in penicillin
      resistance of S. pneumoniae. One widespread family of mosaic pbp2x occurred in
      all three distinct clusters of S. pneumoniae, Streptococcus mitis and
      Streptococcus oralis, documenting independent inter- and intraspecies
      recombination events. Moreover, potential ancestor genes of this mosaic block
      could be identified in two penicillin-susceptible S. mitis strains from South
      Africa and Spain, facilitating the identification of pbp2x mutations relevant for
      resistance development.

PMID- 17459766
TI  - Genetic variation in group A streptococci.
AB  - Group A streptococcus (GAS) is responsible for a range of human diseases that
      vary in their clinical manifestations and severity. While numerous virulence
      factors have been described, the way these factors interact to promote different
      streptococcal diseases is less clear. In order to identify multifactorial
      relationships between GAS and the human host, novel high-throughput techniques
      such as microarrays are necessary. We have performed comparative studies using
      custom-designed virulence arrays to enhance our understanding of the high degree
      of genotypic variation that occurs in streptococci. This study has pointed to
      mobile genetic elements as the major agents that promote variation. Our results
      show that multiple combinations of genes might bring about similar clinical
      pictures. This adds further complexity to the intricate relationship between
      pathogen and host.

PMID- 17459767
TI  - Albomycin is an effective antibiotic, as exemplified with Yersinia enterocolitica
      and Streptococcus pneumoniae.
AB  - Albomycin belongs to the class of sideromycins, compounds composed of iron
      carriers linked to antibiotic moieties. Albomycin was found to be active against
      bacteria that have a functional ferric hydroxamate transport system meaning that
      bacteria will actively transport albomycin until they die. We examined the
      activity spectrum of albomycin for bacterial pathogens and found that
      Enterobacteriaceae except species of Proteus and Morganella were sensitive.
      Resistance in the two genera was due to the lack of the ferric hydroxamate
      transport system. Among Gram-positive bacteria, Staphylococcus aureus and
      Streptococcus pneumoniae were highly sensitive, whereas Streptococcus agalactiae,
      Streptococcus pyogenes, and Staphylococcus epidermidis were resistant. The in
      vivo efficacy of albomycin was examined in mice infected with S. pneumoniae or
      Yersinia enterocolitica. A single dose of 10mg albomycin/kg body weight reduced
      the colony-forming units of Y. enterocolitica by three to four orders of
      magnitude. A single dose of 1mg albomycin/kg body weight was sufficient to clear
      S. pneumoniae infections in mice. In direct competition experiments with wild
      type S. pneumoniae and its albomycin-resistant mutant, the recovery rate of the
      mutant was lower than for the wild-type indicating that the mutant had reduced
      fitness in the mouse model. We conclude that albomycin is effective in clearing
      infections caused by both Gram-positive and Gram-negative bacteria in a mouse
      model. Albomycin treatment reduces the bacterial load allowing the immune system
      to remove residual albomycin-resistant bacteria, and as such would make albomycin
      based antibiotics an adjunct to treatment. The ferrichrome transport system
      serves as a Trojan horse to get albomycin into bacteria.

PMID- 17459768
TI  - Innate immune recognition on the intestinal mucosa.
AB  - The discovery of transcriptionally activating receptors for microbial structures
      has provided a deeper understanding of how the immune system manages to sense and
      localize the presence of harmful microbes and target and shape the adequate host
      response. However, the recognized microbial structures are common to pathogens
      and commensal microbes and many body surfaces are constantly exposed to
      environmental microbial ligands and densely colonized by a bacterial flora such
      as seen for example in the intestinal tract. Thus, mechanisms must exist that
      facilitate discrimination between benign and beneficial colonization and
      potentially harmful invasive infection. Identification of the mechanisms involved
      and characterization of the underlying molecular processes will add to our
      understanding of mucosal immune defense and might unravel the etiology and
      pathogenesis of so far undefined inflammatory conditions. Here, we will discuss
      factors that might be involved to control inappropriate innate immune activation
      and ensure the host-microbe homeostasis in the intestinal tract.

PMID- 17459769
TI  - Are antibiotic-resistant Pseudomonas aeruginosa isolated from hospitalised
      patients recovered in the hospital effluents?
AB  - Previous reports have studied the presence of antibiotic-resistant Pseudomonas
      aeruginosa strains in hospital wastewater without determination of their clonal
      relationship with the clinical strains of this species. The objectives of this
      study were to quantify the presence of P. aeruginosa in wastewater of our
      hospital, to determine their antibiotic-resistance profile and to potentially
      trace clinical antibiotic-resistant strains from patients to wastewater.
      Specimens were taken at the end of the wastewater network of our hospital just
      before the reject in the collective network of the town. Two specimens were taken
      each Monday during 12 weeks. All P. aeruginosa isolates recovered from
      hospitalised patients during the study period were collected. Genotyping of both
      clinical and wastewater isolates was determined by using pulsed-field gel
      electrophoresis (PFGE). The antibiotic-resistance profile of wastewater isolates
      was different from that of clinical isolates. The mechanisms involved in
      antibiotic resistance were different according to the origin of the isolates
      (wastewater versus human isolates). There was no common PFGE pattern in
      antibiotic-resistant P. aeruginosa from humans and wastewater. This study
      suggests that the risk of spread of antibiotic resistance in hospital wastewater
      is limited.

PMID- 17459770
TI  - Paroxysmal supraventricular tachycardia: a century of progress.
AB  - This article reviews progress in the understanding of AV junctional reentrant
      tachycardia and accessory pathway-mediated tachycardia in the twentieth century
      and in the early part of the twenty-first century. Emphasis is placed on the
      contributions of John Uther and the department he founded at Westmead Hospital.

PMID- 17459771
TI  - Assessment of efficacy of pharmacotherapy for ventricular tachycardia.
AB  - The presence and sinister prognosis of sustained ventricular tachycardia was
      recognised early in the twentieth century in patients with serious cardiac
      disease. Treatment was difficult and evolved slowly. The development of
      antiarrhythmic drug therapy was frequently based on chance clinical observations
      and on the assessment of drug effects in animal models of arrhythmia that bore
      little resemblance to the actual clinical scenarios in which the drugs were to be
      employed. Even early reports of antiarrhythmic drug use were tempered by
      awareness of serious adverse side effects. Many drugs were brought into wide
      spread clinical use without the background of large randomised trials of
      efficacy. Assessment of drug efficacy for ventricular tachycardia was frequently
      based on the effects of an administered drug on inducibility of tachycardia with
      invasive electrophysiologic techniques. Suppression of inducibility was suggested
      to be a marker of drug efficacy. Similarly, suppression of spontaneously
      occurring ventricular ectopic beats was also used as a predictor of drug effect.
      However, both predictive techniques were hindered by inherent baseline
      variability. It was subsequently demonstrated that mode of induction of
      ventricular tachycardia could vary widely at repeat inductions. Antiarrhythmic
      drugs rarely suppressed inducibility of VT but could alter mode of induction.
      Techniques were developed to estimate true drug effects by quantitating and
      allowing for random variability in mode of tachycardia induction. In particular,
      reproducibility of tachycardia induction was enhanced when baseline and drug
      studies were performed at short intervals. Even with these techniques, prediction
      of long-term drug efficacy in individual patients remained difficult and acute
      drug testing served principally to demonstrate the fact that drug therapy was
      more likely to facilitate induction of tachycardia than to suppress it (pro
      arrhythmic effect). Large clinical trials also demonstrated the potent pro
      arrhythmic effects of drug therapy especially when sodium-channel blocking drugs
      were used. By the end of the twentieth century, antiarrhythmic drugs were used
      primarily as adjuncts to device therapy for patients at risk of life-threatening
      ventricular arrhythmias.

PMID- 17459772
TI  - Unravelling the moulting degradome: new opportunities for chemotherapy?
AB  - Replacement of the nematode cuticle with a newly synthesized cuticle (a process
      known as moulting) occurs four times during larval development. Therefore, the
      key components of this essential developmental process represent attractive
      targets for new chemotherapeutic strategies. Recent advances in understanding the
      molecular genetics of nematode moulting should stimulate and facilitate
      development of novel drugs that target the essential molecules of the moulting
      cycle. In particular, we argue that further understanding of the moulting
      degradome and its key peptidase members offers an important opportunity for the
      development of novel antinematode agents.

PMID- 17459773
TI  - Where next with Loa loa encephalopathy? Data are badly needed.

PMID- 17459774
TI  - Response to Horn: Introducing histone modifications in trypanosomes.

PMID- 17459775
TI  - Plasmodium malariae and Plasmodium ovale--the "bashful" malaria parasites.
AB  - Although Plasmodium malariae was first described as an infectious disease of
      humans by Golgi in 1886 and Plasmodium ovale identified by Stevens in 1922, there
      are still large gaps in our knowledge of the importance of these infections as
      causes of malaria in different parts of the world. They have traditionally been
      thought of as mild illnesses that are caused by rare and, in case of P. ovale,
      short-lived parasites. However, recent advances in sensitive PCR diagnosis are
      causing a re-evaluation of this assumption. Low-level infection seems to be
      common across malaria-endemic areas, often as complex mixed infections. The
      potential interactions of P. malariae and P. ovale with Plasmodium falciparum and
      Plasmodium vivax might explain some basic questions of malaria epidemiology, and
      understanding these interactions could have an important influence on the
      deployment of interventions such as malaria vaccines.

PMID- 17459776
TI  - Small world - advance of microarrays: current status and future trends.
AB  - Microarrays have the potential to become the next generation blood-testing
      platform. This commentary covers various aspects of such development presented in
      part at the Scotblood 2006 Meeting. Current mandatory testing includes antibody
      and antigen determination in both blood grouping and microbiology testing. While
      antibody determination is limited to phenotypic assays, antigen detection can be
      accomplished by genotyping or phenotyping. Applicability of various types of
      assays to microarrays, precision and sensitivity levels and correlation between
      genotyping and phenotyping results are briefly discussed and some of the main
      questions that need to be answered highlighted in future trends.

PMID- 17459777
TI  - Preterm labour. The present and future of tocolysis.
AB  - This chapter discusses the tocolytic agents currently in use for the treatment of
      preterm labour and considers them in light of the evidence base. These agents are
      the beta2 sympathomimetic agonists, magnesium sulphate (MgSO(4)), indomethacin,
      nifedipine and atosiban. The available evidence for these agents shows that the
      beta2 agents are effective but have significant maternal side effects and no
      effect on perinatal outcome. MgSO(4) and glyceryl trinitrate are clearly
      ineffective. Nifedipine is effective with a low maternal side effect profile and
      is associated with improved perinatal outcomes. Meta-analyses of the several
      randomized controlled trials of atosiban show that it is no more effective than
      other tocolytic therapies. Possible directions for the future will be discussed.

PMID- 17459778
TI  - First-generation endometrial ablation: roller-ball vs loop vs laser.
AB  - Hysteroscopic guided or first generation endometrial ablation methods include
      transcervical endometrial resection, and rollerball and laser ablation. These
      techniques have been shown to be effective and safe alternatives to hysterectomy
      for dysfunctional uterine bleeding resulting in reduction in menstrual blood loss
      and dysmenorrhoea, correction of anaemia and improvement in quality of life.
      Compared with hysterectomy, treatment is associated with lower morbidity, shorter
      hospitalisation and faster recovery, and reduced treatment costs. As a result,
      the 1st generation ablation techniques are recognized as the "gold standard"
      ablation methods. There are many similarities between the three techniques with
      respect to surgical principles and effectiveness. Certainly, menstrual
      improvement and patient satisfaction are similar with all three methods. In
      contrast, the complication profile of the three techniques is different, but
      surgical experience is arguably a much more important arbiter of patient safety
      than the technique itself.

PMID- 17459779
TI  - The clinical applications of myocardial contrast echocardiography.
AB  - Recent updates in the field of echocardiography have resulted in improvements in
      both image quality and techniques allowing echocardiography to maintain it's
      position as the primary non-invasive imaging modality. In particular, the
      development of new ultrasound contrast agents and imaging techniques have now
      made possible the assessment of myocardial perfusion. Myocardial contrast
      echocardiography utilises acoustically active gas filled microspheres
      (microbubbles), which have rheology similar to that of red blood cells. The
      detection of myocardial perfusion during echocardiographic examinations permits
      simultaneous assessment of global and regional myocardial structure, function,
      and perfusion, enabling the optimal non-invasive assessment of coronary artery
      disease. Myocardial contrast echocardiography is equally adept in assessing
      chronic coronary artery disease, acute coronary syndromes and hibernating
      myocardium.

PMID- 17459780
TI  - Pattern and frequency of use of complementary and alternative medicine among
      patients with epilepsy in the midwestern United States.
AB  - Complementary and alternative medicine (CAM) is recognized to be commonly used by
      patients, yet there have been few studies regarding the scope of CAM use by
      patients with epilepsy. This study assessed usage and perceptions of CAM by
      patients with epilepsy in the midwest of the United States. A 25-item survey was
      administered to adult patients with epilepsy, and data were collected from 228
      patients. The survey collected demographics, specific CAM usage, adverse effects
      of CAM therapy, and perceptions of the effectiveness of CAM. Thirty-nine percent
      reported using CAM; 25% reported using CAM specifically for their epilepsy.
      Prayer/spirituality was the most commonly used form of CAM (46%), followed by
      "mega" vitamins (25%), chiropractic care (24%), and stress management (16%). CAM
      use is common among midwestern patients with epilepsy, although the pattern of
      use may be slightly different than in other regions of the United States and
      elsewhere.

PMID- 17459781
TI  - The relaxant effect of curcumin on porcine coronary arterial ring segments.
AB  - Curcumin is a naturally occurring phenolic compound isolated as a yellow pigment
      from turmeric (curcuma longa). This compound has received much attention due to
      its diversity of biological and pharmacological activities. The purpose of this
      study was to assess the effect of curcumin on porcine coronary arteries and to
      investigate the mechanism of its action, if any. The isometric tension of
      coronary arterial rings taken from porcine hearts was measured and its response
      to curcumin (10(-11)-10(-5) mol/l) was studied. It was found that curcumin
      significantly reduced the isomeric tension of both quiescent and prostaglandin
      F2alpha (PGF2alpha) precontracted porcine coronary arterial rings. The relaxing
      effect of curcumin on coronary arteries was significantly reduced by removal of
      endothelium, and by the addition of N-nitro-L-arginine (L-NNA), methylene blue or
      propranolol, but not by indomethacin. These results suggest that curcumin-induced
      relaxation of isolated porcine coronary arteries might involve the action of
      nitric oxide (NO), cyclic guanosine monophosphate (cGMP) and adrenergic beta
      receptor, but not involve the synthesis of prostaglandin.

PMID- 17459782
TI  - Vasoconstriction of porcine left anterior descending coronary artery by ecstasy
      and cathinone is not an indirect sympathomimetic effect.
AB  - 3,4-methylenedioxymethamphetamine ('Ecstasy', MDMA) and cathinone, the active
      constituent of khat leaves, were examined on pig isolated left anterior
      descending coronary arteries to determine whether they cause vasoconstriction and
      whether this was an indirect sympathomimetic action. Coronary artery rings were
      set up in Krebs solution (37 degrees C) gassed with 5% CO2 in O2. Endothelium
      remained intact as indicated by relaxation by bradykinin. Isometric tension was
      recorded and cumulative concentration-response curves (CRCs) for noradrenaline,
      ecstasy or cathinone plotted as a percent of the constriction to KCl (60 mM).
      Noradrenaline-induced contractions of the coronary artery were enhanced by
      propranolol (1 microM) indicating beta-adrenoceptor-mediated opposing
      vasodilatation. Cocaine (10 microM) further potentiated, while prazosin (1
      microM) virtually abolished the contractions to noradrenaline. Cathinone and
      ecstasy constricted the coronary artery rings, the peak contractions being 56.5+/
      4.2% (n=4) and 37.3+/-2.4% (n=4), respectively. Higher concentrations relaxed.
      The vasoconstriction was not affected by cocaine (10 microM), prazosin (1 microM,
      in the presence of cocaine) or removal of the endothelium. There was no
      tachyphylaxis or desensitisation on repeated administration of single doses.
      Ecstasy- and cathinone-induced coronary vasoconstriction is therefore via
      mechanisms other than indirect sympathomimetic activity or alpha1 -adrenoceptors.
      This activity could explain the cardiac adverse effects following their excessive
      use.

PMID- 17459783
TI  - A randomized trial of PET scanning to improve diagnostic yield of direct
      laryngoscopy in patients with suspicion of recurrent laryngeal carcinoma after
      radiotherapy.
AB  - The RELAPS study (REcurrent LAryngeal carcinoma PET Study) was designed to
      determine whether FDG-PET is of value in the selection of patients for direct
      laryngoscopy under general anesthesia in patients with suspicion of recurrent
      laryngeal carcinoma after radiotherapy. In a randomized controlled clinical trial
      the current diagnostic practice, i.e. all patients undergo direct laryngoscopy,
      will be compared to a strategy in which FDG-PET selects the patients for
      laryngoscopy. All eight head and neck cancer centers of the Dutch Head and Neck
      Oncology Cooperative Group NWHHT will participate in this multicenter trial. The
      study population consists of patients with clinical suspicion of recurrent T2-T4
      laryngeal carcinoma after radiotherapy (without obvious signs of tumor) in whom a
      direct laryngoscopy under general anesthesia with taking of biopsies is indicated
      by the local physician. The primary efficacy endpoint is the difference in the
      number of futile indications for direct laryngoscopy between the conventional
      diagnostic arm and the FDG-PET based diagnostic arm. An indication for
      laryngoscopy is classified as futile if this laryngoscopy was negative and no
      recurrence was diagnosed within 6 months follow-up (gold standard). The FDG-PET
      based strategy may increase the risk of missing recurrent tumor compared to
      current practice. Safety endpoints include survival and morbidity due to
      laryngoscopy with taking of biopsies. Survival rates of both groups will have to
      be collected outside the time frame of the funded trial. Resectability of
      recurrent tumor and tumor negative surgical margins after total laryngectomy will
      be used as proxy endpoints. The trial will also compare quality of life and
      direct medical costs between both arms.

PMID- 17459784
TI  - Randomized controlled trials of positive affect and self-affirmation to
      facilitate healthy behaviors in patients with cardiopulmonary diseases:
      rationale, trial design, and methods.
AB  - Secondary prevention of adverse outcomes in patients with cardiopulmonary disease
      requires that patients become actively engaged in self-management efforts such as
      participation in physical activity or medication adherence. However, despite
      assiduous efforts to find strategies that help cardiovascular patients to adopt
      and maintain such behaviors, many studies of interventions designed to improve
      physical activity and adherence to medication have shown disappointing results.
      To this end, the Translational Behavioral Science Research Consortium was created
      by the National Heart, Lung, and Blood Institute to identify promising, but
      underutilized findings from basic behavioral science that might have potential
      application for translation to clinical populations where behavioral change has
      been refractory to standard intervention approaches. This paper describes the
      rationale and methods of a novel research project designed to test the efficacy
      of a behavioral intervention that combines constructs from two behavioral science
      theories (positive affect and self-affirmation) in order to help patients with
      coronary artery disease, asthma, and hypertension successfully change behaviors.
      The project consists of an intervention framed upon positive affect and self
      affirmation and tested in three concurrent randomized controlled trials among
      three distinct populations. Each trial had a qualitative phase that served as a
      formative stage to inform the intervention; a pilot phase during which the
      feasibility of the intervention was tested and refined; and a randomized
      controlled phase conducted to investigate the effects of the interventions in
      these three patient groups.

PMID- 17459785
TI  - Simultaneous determination of metformin and rosiglitazone in human plasma by
      liquid chromatography/tandem mass spectrometry with electrospray ionization:
      application to a pharmacokinetic study.
AB  - A selective and sensitive high performance liquid chromatography-electrospray
      ionization-tandem mass spectrometry (ESI-MS/MS) method for simultaneous
      determination of metformin and rosiglitazone in human plasma using phenformin as
      internal standard (IS) has been first developed and validated. Plasma samples
      were precipitated by acetonitrile and the analytes were separated on a prepacked
      Phenomenex Luna 5u CN 100A (150 mm x 2.0 mm I.D.) column using a mobile phase
      comprised of methanol:30 mM ammonium acetate pH 5.0 (80:20, v/v) delivered at 0.2
      ml/min. Detection was performed on a Finnigan TSQ triple-quadrupole tandem mass
      spectrometer in positive ion selected reaction monitoring (SRM) mode using
      electrospray ionization. The ion transitions monitored were m/z 130.27-->71.11
      for metformin, m/z 358.14-->135.07 for rosiglitazone and m/z 206.20-->105.19 for
      the IS. The standard curves were linear (r(2)>0.99) over the concentration range
      of 5-3000 ng/ml for metformin and 1.5-500 ng/ml for rosiglitazone with acceptable
      accuracy and precision, respectively. The within- and between-batch precisions
      were less than 15% of the relative standard deviation. The limit of detection
      (LOD) of both metformin and rosiglitazone was 1 ng/ml. The method described is
      precise and sensitive and has been successfully applied to the study of
      pharmacokinetics of compound metformin and rosiglitazone capsules in 12 healthy
      Chinese volunteers.

PMID- 17459786
TI  - Automated liquid chromatography-tandem mass spectrometry method for the analysis
      of firocoxib in urine and plasma from horse and dog.
AB  - A rugged, sensitive and efficient liquid chromatography-tandem mass spectrometry
      method was developed and validated for the quantitative analysis of firocoxib in
      urine from 5 to 3000 ng/mL and in plasma from 1 to 3000 ng/mL. The method
      requires 200 microL of either plasma or urine and includes sample preparation in
      96-well solid phase extraction (SPE) plates using a BIOMEK 2000 Laboratory
      Automated Workstation. Chromatographic separation of firocoxib from matrix
      interferences was achieved using isocratic reversed phase chromatography on a
      PHENOMENEX LUNA Phenyl-Hexyl column. The mobile phase was 45% acetonitrile and
      55% of a 2 mM ammonium formate buffer. The method was accurate (88-107%) and
      precise (CV<12.2%) within and between sets. Extraction efficiencies
      (recovery)>93% were achieved and ionization efficiencies (due to matrix effects)
      were >72%. Extensive stability and ruggedness testing was also performed;
      therefore, the method can be used for pharmacokinetic studies as well as drug
      monitoring and screening. The data presented here is the first LC-MS/MS method
      for the quantitation of firocoxib in plasma (LLOQ of 1 ng/mL), a 25-fold
      improvement in sensitivity over the HPLC-UV method and the first quantitative
      method for firocoxib in urine (LLOQ of 5 ng/mL). Additionally the sample
      preparation process has been automated to improve efficiency.

PMID- 17459787
TI  - Two-step method to isolate target recombinant protein from co-purified bacterial
      contaminant SlyD after immobilised metal affinity chromatography.
AB  - As part of a study to purify the internal domain of HER2 (ICD) from recombinant
      expression, through metal immobilised affinity chromatography (IMAC), we
      encountered a contaminant, SlyD, a 29 kDa native E. coli protein. SlyD is a
      recurrent contaminant, with a histidine rich domain enabling binding to IMAC
      columns and thus co-elution with the target protein. Research has been carried
      out on this protein and its purification, however, no work mentions how to treat
      it as a true contaminant or describe procedures to isolate it from target
      proteins. In this report, we described a two-step chromatographic method for the
      purification of ICD, including IMAC as a capture step and size exclusion
      chromatography (SEC) as a polishing step. IMAC allowed us to purify ICD from
      bacterial crude with SlyD co-eluting. SEC then allowed us to resolve ICD from
      SlyD and achieve a purity greater than 95% for ICD. However, this method has been
      developed to accommodate any protein whose molecular weight is different enough
      from SlyD to be separated by SEC.

PMID- 17459788
TI  - Determination of raltitrexed in human plasma by high performance liquid
      chromatography-electrospray ionization-mass spectrometry.
AB  - A sensitive high performance liquid chromatography-electrospray ionization-mass
      spectrometry (HPLC-ESI-MS) assay was developed to determine raltitrexed in human
      plasma. After addition of benazeprilat as the internal standard (IS), methanol
      was used to produce a protein-free extract. Chromatographic separation was
      achieved with a Zorbax SB-C18 column (Narrow-Bore 2.1 mmx150 mm, 5-microm) using
      a mobile phase of acetonitrile-water containing 0.1% formic acid and 2% methanol
      (21.9:78.1, v/v). Raltitrexed was determined with electrospray ionization-mass
      spectrometry. HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode
      using target ions at [M+H]+ m/z 459.1 for raltitrexed and [M+H]+ m/z 397.1 for
      IS. Calibration curves were linear over the range of 2.0-3000 ng/ml. The lower
      limit of quantification was 2.0 ng/ml. The intra- and inter-batch variability
      values were less than 6.7% and 10.3%, respectively. The mean plasma extraction
      recovery of raltitrexed was in the range of 85.2-91.1%. The method was
      successfully applied to determine the plasma concentrations of raltitrexed in
      eight Chinese colorectal cancer patients.

PMID- 17459789
TI  - Simple and simultaneous determination for 12 phenothiazines in human serum by
      reversed-phase high-performance liquid chromatography.
AB  - A high-performance liquid chromatographic method has been developed for the
      simultaneous analysis of the 12 phenothiazines (chlorpromazine, fluphenazine,
      levomepromazine, perazine, perphenazine, prochlorperazine, profenamine,
      promethazine, propericiazine, thioproperazine, thioridazine and trifluoperazine)
      in human serum using HPLC/UV. The separation was achieved using a C(18) reversed
      phase column (250 mm x 4.6 mm I.D., particle size 5 microm, Inersil ODS-SP). The
      mobile phase, consisting of acetonitrile-methanol-30 mM NaH(2)PO(4) (pH 5.6)
      (300:200:500, v/v/v), was delivered at a flow rate of 0.9 mL/min and UV detection
      was carried out at 250 nm. The recoveries of the 12 phenothiazines spiked into
      serum samples were 87.6-99.8%. Regression equations for the 12 phenothiazines
      showed excellent linearity, with detection limits of 3.2-5.5 ng/mL for serum. The
      inter-day and intra-day coefficients of variation for serum samples were commonly
      below 8.8%. The selectivity, accuracy and precision of this method are
      satisfactory for clinical and forensic purposes. This sensitive and selective
      method offers the opportunity for simultaneous screening and quantification of
      almost all phenothiazines available in Japan for the purposes of clinical and
      forensic applications.

PMID- 17459791
TI  - Synaptonemal complex protein SYCP3: Conserved polymerization properties among
      vertebrates.
AB  - Synaptonemal complexes (SCs) are meiosis-specific, nuclear structures that are
      critically involved in synapsis, recombination and segregation of homologous
      chromosomes. Although the SC structure is conserved in evolution this is not the
      case for its protein components. To provide information on SC proteins which
      would be important for our understanding of the conserved SC structure and
      function, here we compared ortholog SYCP3 proteins of two evolutionary distant
      vertebrate species, namely rat and medaka fish. To this end we have investigated
      the polymerization properties of both proteins by immunocytochemistry, electron
      microscopy and cell fractionation. We found that despite of the sequence
      differences that have accumulated over the last 450 million years mammalian and
      fish SYCP3 have similar properties that allow them to co-assemble higher order
      structures under experimental conditions. We also provide a likely explanation as
      to how heterozygous mutations in the SYCP3 gene can lead to a defective meiosis.

PMID- 17459793
TI  - Transit times in capsule endoscopy: are all patients the same?

PMID- 17459794
TI  - COXIBs and non-selective NSAIDs in the gastroenterological setting: what should
      patients and physicians do?
AB  - Although adverse effects of nonsteroidal anti-inflammatory drugs occur in only a
      small proportion of users, the widespread use of these drugs has resulted in a
      substantial overall number of affected persons who experience serious
      gastrointestinal complications. Dyspeptic symptoms are estimated to occur in 10
      60% of nonsteroidal anti-inflammatory drug users and lead to discontinuation of
      treatment in 5-15% of rheumatoid arthritis patients taking nonsteroidal anti
      inflammatory drugs. It is now well established that the point prevalence of
      peptic ulcer disease in patients receiving conventional nonsteroidal anti
      inflammatory drug therapy ranges between 10 and 30%, representing a 10- to 30
      fold increase over that found in the general population. One out of 175 users of
      conventional nonsteroidal anti-inflammatory drugs in the USA will be hospitalized
      each year for nonsteroidal anti-inflammatory drug-induced gastrointestinal
      damage. The mortality of hospitalized patients remains about 5-10%, with an
      expected annual death rate of 0.08%. The selective COX-2 inhibitors consistently
      show comparable efficacy to that of conventional nonsteroidal anti-inflammatory
      drugs in patients with rheumatoid arthritis and osteoarthritis, but have a
      reduced propensity to cause gastrointestinal toxicity. In many cases, the gastric
      effects of therapeutically active doses of COX-2 inhibitors are indistinguishable
      from placebo. The safety benefits of COX-2 inhibitors given alone appear similar
      to those of combined therapy with conventional nonsteroidal anti-inflammatory
      drugs and gastroprotective agents. These findings warrant the consideration of
      COX-2 inhibitors as first-line therapy in patients requiring long-term pain
      control.

PMID- 17459792
TI  - Sulfite oxidizing enzymes.
AB  - Sulfite oxidizing enzymes are essential mononuclear molybdenum (Mo) proteins
      involved in sulfur metabolism of animals, plants and bacteria. There are three
      such enzymes presently known: (1) sulfite oxidase (SO) in animals, (2) SO in
      plants, and (3) sulfite dehydrogenase (SDH) in bacteria. X-ray crystal structures
      of enzymes from all three sources (chicken SO, Arabidopsis thaliana SO, and
      Starkeya novella SDH) show nearly identical square pyramidal coordination around
      the Mo atom, even though the overall structures of the proteins and the presence
      of additional cofactors vary. This structural information provides a molecular
      basis for studying the role of specific amino acids in catalysis. Animal SO
      catalyzes the final step in the degradation of sulfur-containing amino acids and
      is critical in detoxifying excess sulfite. Human SO deficiency is a fatal genetic
      disorder that leads to early death, and impaired SO activity is implicated in
      sulfite neurotoxicity. Animal SO and bacterial SDH contain both Mo and heme
      domains, whereas plant SO only has the Mo domain. Intraprotein electron transfer
      (IET) between the Mo and Fe centers in animal SO and bacterial SDH is a key step
      in the catalysis, which can be studied by laser flash photolysis in the presence
      of deazariboflavin. IET studies on animal SO and bacterial SDH clearly
      demonstrate the similarities and differences between these two types of sulfite
      oxidizing enzymes. Conformational change is involved in the IET of animal SO, in
      which electrostatic interactions may play a major role in guiding the docking of
      the heme domain to the Mo domain prior to electron transfer. In contrast, IET
      measurements for SDH demonstrate that IET occurs directly through the protein
      medium, which is distinctly different from that in animal SO. Point mutations in
      human SO can result in significantly impaired IET or no IET, thus rationalizing
      their fatal effects. The recent developments in our understanding of sulfite
      oxidizing enzyme mechanisms that are driven by a combination of molecular
      biology, rapid kinetics, pulsed electron paramagnetic resonance (EPR), and
      computational techniques are the subject of this review.

PMID- 17459795
TI  - Management of large volume CT contrast medium extravasation injury: technical
      refinement and literature review.
AB  - The incidence of radiographic contrast medium extravasation is on the rise due to
      the rapid increase in availability of contrast enhanced imaging. There is no
      consensus, however, regarding its management. There is a wide spectrum of
      clinical presentations, ranging from localised erythema and oedema to skin
      necrosis, which is related to the osmolarity and volume of the extravasated
      contrast medium. It is not possible to predict the degree of final tissue injury
      at initial examination. The increase in use of automated bolus injection has led
      to an increase in incidence of large volume extravasation injuries. Here we
      present a review of the literature regarding clinical presentation, risk factors,
      and management of contrast extravasation injuries. We also report the management
      of a large volume computed tomography contrast extravasation injury following
      mechanical bolus injection using a combination of liposuction and saline washout
      as described by Gault, and the use of compression by a Rhys-Davies exsanguinator
      as a technical refinement to achieve immediate resolution of the soft tissue
      oedema.

PMID- 17459796
TI  - Functional transposition of the latissimus dorsi muscle for biceps reconstruction
      after upper arm replantation.
AB  - Major upper arm amputations are often accompanied by different levels of soft
      tissue divisions involving crushing, traction, and avulsion injuries to various
      structures. In these cases the goal is not only the re-establishment of
      circulation, but also functional outcome. Some patients require further
      reconstruction for functional restoration of elbow flexion and additional soft
      tissue coverage. Five patients underwent functional latissimus dorsi transfer for
      restoration of elbow flexion after successful upper arm replantation at our
      institution. The transfer was unipolar in four patients and bipolar in one. The
      patients' ages ranged from seven to 55 years. The time period between
      replantation and transfer ranged from two weeks to 12 months. All flaps healed
      well with minimal donor site morbidity. At mean 43-month follow-up (range: 22-65
      months), functional results were good with M4 in three patients and M3 in two
      patients for elbow flexion. The pedicled latissimus dorsi muscle flap is a
      valuable tool to restore elbow flexion and provide coverage of soft tissue
      defects after major upper arm replantations.

PMID- 17459797
TI  - Use of acellular cadaveric dermis and tissue expansion in postmastectomy breast
      reconstruction.
AB  - Tissue expander or permanent implant coverage in postmastectomy breast
      reconstruction is often challenging. Multiple authors have demonstrated the use
      of acellular cadaveric dermis (ACD) in nonexpansive, single-stage breast
      reconstruction. The literature also suggests that tissue expansion may be
      accomplished with ACD as well for stage reconstructions. In many cases tissue
      expansion is necessary to create a submuscular and subACD pocket to accommodate a
      subsequent permanent prosthesis. In this study we report the outcomes and
      complication rates of using ACD in staged breast reconstruction. We reviewed the
      charts of 41 patients (65 breasts) in whom ACD was used in staged
      reconstructions. We analysed the patients' charts and operative records to
      determine postoperative complication rates and results. Complication rates for
      wound infection, expander removal, haematoma, and seroma were: 3.1% (two of 65),
      1.5% (one of 65), 1.5% (one of 65), and 4.6% (three of 65), respectively. The use
      of ACD in expansive postmastectomy breast reconstruction has an extremely low
      complication rate, results in good cosmetic outcome, and should be in the
      repertoire of plastic surgeons. Further follow up is needed to evaluate the long
      term outcomes of ACD use in postmastectomy breast reconstruction.

PMID- 17459798
TI  - Sagittal synostosis: a review of 53 cases of sagittal suturectomy in one unit.
AB  - The role of sagittal suturectomy in the treatment of scaphocephaly remains
      controversial. The purpose of this study was to report the experience of the
      National Craniofacial Unit in Dublin. This unit is the referral centre for the
      Republic of Ireland and serves a population of approximately 3.5 million.
      Quantitative assessments were made using radiographs and the pre- and
      postoperative cephalic index (CI) was calculated. Patients were asked to score
      their head shapes in a questionnaire. The mean age at surgery for the 53 children
      was 4.9 months with a mean follow up of 8 years. Pre- and postoperative
      radiographs were available for analysis in 24 patients. The mean preoperative CI
      was 65.3. There was a statistically significant increase in the CI
      postoperatively to 73.7. Seventy five per cent of children achieved a 'normal' CI
      and 86% scored their head shapes as good to excellent. There was no correlation
      between the age at surgery and the CI achieved. Although only one child was not
      happy with the shape of the head, the impression was that the CI correlated
      poorly with the clinical assessment of the head shape. There were no significant
      complications. We therefore conclude that the sagittal suturectomy is a safe
      procedure that has a limited but definite potential to improve the CI. This
      procedure still has a place in the surgical repertoire of the craniofacial
      surgeon dealing with scaphocephaly.

PMID- 17459799
TI  - A free scapular skin flap for penile reconstruction.
AB  - INTRODUCTION: There are many possible methods for penis reconstruction, among
      them, pedicled flaps, myocutaneous flaps, combined osseocutaneous flaps, and free
      skin flaps. This study evaluated the free scapular skin flap method for penile
      reconstruction. METHODS: Fifteen men aged 20 to 48 underwent the procedure
      between March 2000 and February 2006, with follow-up examinations from 6 months
      to 5 years. RESULTS: Fourteen of the reconstructions were successful, with
      patients enjoying good cosmetic results as well as functionality. CONCLUSION: The
      free scapular skin flap technique is a good method for penile reconstruction.

PMID- 17459800
TI  - Proliferating pilomatricoma: a subset of pilomatricoma.
AB  - Proliferating pilomatricoma is a histopathological entity that was proposed by
      Kaddu et al. in 1997. Proliferating pilomatricoma represents a distinctive
      histopathological entity; it should be differentiated from other benign and
      malignant neoplasms with features of hair matrix differentiation. Kaddu reported
      that an incompletely excised proliferating pilomatricoma may have a greater
      potential for local recurrence, because histopathologically it showed variable
      nuclear atypia and several mitotic figures. We report two patients with
      proliferating pilomatricoma and describe their clinical and pathological
      features.

PMID- 17459801
TI  - The role of larger osteotomy in long term success in external
      dacryocystorhinostomy.
AB  - AIM: This study aims to investigate whether it is possible to create a critical
      size bone defect in external dacryocystorhinostomy (DCR), and also at what size a
      defect can be considered as being critical for a successful surgical outcome.
      METHODS: Eighteen patients undergoing 19 external dacryocystorhinostomies, with
      the creation of wide osteotomies, were enrolled in this retrospective study. A 2
      x 2 cm bone defect, which was considered as the critical size, was created. The
      postoperative structure of the bone gap was evaluated by computed tomography in
      axial and coronal planes at least two years after surgery. Functional patency of
      the ostium was confirmed with irrigation and nasal endoscopic examination.
      RESULTS: Thirteen female (72.2%) and five male (27.8%) patients underwent DCR.
      The patients were aged between 18 and 72 years old (mean+/-S.D.: 45.3+/-13.9).
      The follow-up time was between 24 and 48 months (mean 30.4 months). The areas of
      the gaps were between 1.21 and 4 cm(2) (mean+/-S.D.: 2.26+/-0.19). CONCLUSION:
      The critical size bone defect (2 x 2 cm) might prevent restenosis in long term
      follow ups.

PMID- 17459802
TI  - HSA: beyond BMD with DXA.
AB  - The measurement of bone mineral density is a surrogate for the measurement of
      bone strength. Bone strength is comprised of many components including, but not
      limited to bone architecture, geometry, cortical porosity and tissue
      mineralization density. A new application for dual energy X-ray absorptiometry
      (DXA), called hip structural or hip strength analysis (HSA), allows the
      measurement of geometric contributions to bone strength in the proximal femur.
      With this approach, the cross-sectional area, section modulus and buckling ratio
      can be quantified. These parameters are measures of strength in axial compression
      or bending. The limitations of HSA with DXA are primarily those associated with
      the two-dimensional nature of DXA. Because of the two-dimensional nature of DXA,
      assumptions must be made regarding the symmetry of the bone cross-sections used
      in the HSA regions of interest. In one proprietary approach to HSA, an index,
      called the Femur Strength Index, has been created in an attempt to relate the
      force of a fall on the greater trochanter to the strength of the proximal femur.
      Studies using HSA with DXA have demonstrated discordant behaviors between the
      bone mineral density (BMD) and the section modulus. The geometric parameters are
      predictive of fracture risk although they do not seem to be better predictors of
      risk than a conventional measurement of BMD. Various bone active agents have been
      shown to have desirable effects on these geometric parameters. Direct measurement
      of these components of bone strength may result in improved fracture risk
      prediction or therapeutic monitoring. Minimally, a better understanding of the
      changes in these components of bone strength in disease and during therapy may
      result from HSA.

PMID- 17459804
TI  - A signal for the caspase-1 inflammasome free of TLR.
AB  - Secretion of the proinflammatory cytokine IL-1beta requires caspase-1 and Toll
      like receptor (TLR) signaling. However, Kanneganti et al. (2007) find that
      bacteria can use pore-forming mechanisms to activate caspase-1 for the production
      of IL-1beta precursor independently of TLRs.

PMID- 17459805
TI  - Ready for prime time: NK cell priming by dendritic cells.
AB  - Natural killer (NK) cells were long thought to respond directly to infected cells
      and tumor cells. In this issue of Immunity, Lucas et al. (2007) repeal this view
      by showing that NK cells acquire functionality through priming by dendritic
      cells.

PMID- 17459803
TI  - Reconciling the roles of FAK in osteoblast differentiation, osteoclast
      remodeling, and bone regeneration.
AB  - Integrins link the inside of a cell with its outside environment and in doing so
      regulate a wide variety of cell behaviors. Integrins are well known for their
      roles in angiogenesis and cell migration but their functions in bone formation
      are less clear. The majority of integrin signaling proceeds through focal
      adhesion kinase (FAK), an essential component of the focal adhesion complex. We
      generated transgenic mice in which FAK was deleted in osteoblasts and uncovered a
      previously unknown role in osteoblast differentiation associated with bone
      healing. FAK mutant cells migrated to the site of skeletal injury and
      angiogenesis was unaffected yet the transgenic mice still exhibited numerous
      defects in reparative bone formation. Osteoblast differentiation itself was
      unperturbed by the loss of FAK, whereas the attachment of osteoclasts to the bone
      matrix was disrupted in vivo. We postulate that defective bi-directional integrin
      signaling affects the organization of the collagen matrix. Finally, we present a
      compensatory candidate molecule, Pyk2, which localized to the focal adhesions in
      osteoblasts that were lacking FAK.

PMID- 17459806
TI  - Antigen to the node: B cells go native.
AB  - The participation of B and T cells in an immune response requires their separate
      activation by different forms of the target antigen. In this issue of Immunity,
      Pape et al. (2007) describe antigen entry into the B cell areas in the lymph node
      without degradation or cellular assistance.

PMID- 17459807
TI  - Hold on, the monocytes are coming!
AB  - The role that monocyte-derived dendritic cells play in vivo remains enigmatic.
      Leon et al. (2007) now show that these cells develop "on demand" at a site of
      Leishmania infection to promote a life-saving T helper 1 immune response.

PMID- 17459808
TI  - Neuroregulator RET initiates Peyer's-patch tissue genesis.
AB  - The tyrosine kinase receptor RET regulates the intestinal nervous system. A
      recent paper by Veiga-Fernandes et al. (2007) demonstrates that RET is also
      involved in the intestinal immune system through the initiation of Peyer's-patch
      tissue genesis.

PMID- 17459809
TI  - The final touches make perfect the peptide-MHC class I repertoire.
AB  - Major histocompatibility complex (MHC) class I molecules present short, perfectly
      cleaved peptides on the cell surface for immune surveillance by CD8(+) T cells.
      The pathway for generating these peptides begins in the cytoplasm, and the
      peptide-MHC I (pMHC I) repertoire is finalized in the endoplasmic reticulum.
      Recent studies show that the peptides for MHC I are customized by the ER
      aminopeptidase associated with antigen processing and by dynamic interactions
      within the MHC peptide-loading complex. Failure to customize the pMHC I
      repertoire has profound immunological consequences.

PMID- 17459812
TI  - Nursing and other health care disciplines have a longstanding tradition of
      conscientious objection.

PMID- 17459813
TI  - Israeli nurses and genetic information disclosure.
AB  - The debate continues about whether people have a duty to pass on the positive
      results of their genetic tests to relatives who are at risk from the same
      disease, and, should they refuse, whether physicians and genetic counselors then
      have the duty to do so. To date, the role and views of nurses in this debate have
      not been investigated. In our study, a sample of Israeli nurses, untrained in
      genetics, were asked for their theoretical opinions and what practical steps they
      would take in the case of patients' refusal to disclose. The nurses were very
      sure that patients should inform their families but were equally sure that nurses
      must respect their decision to disclose or not. Few said they would take
      practical steps to disclose information if the patient objected. The authors
      believe that the most useful and appropriate role for nurses in this field is in
      working to bring about co-operation between patients and family members.

PMID- 17459810
TI  - Vaccine-induced pathogen strain replacement: what are the mechanisms?
AB  - Host immune systems impose natural selection on pathogen populations, which
      respond by evolving different antigenic signatures. Like many evolutionary
      processes, pathogen evolution reflects an interaction between different levels of
      selection; pathogens can win in between-strain competition by taking over
      individual hosts (within-host level) or by infecting more hosts (population
      level). Vaccination, which intensifies and modifies selection by protecting hosts
      against one or more pathogen strains, can drive the emergence of new dominant
      pathogen strains-a phenomenon called vaccine-induced pathogen strain replacement.
      Here, we review reports of increased incidence of subdominant variants after
      vaccination campaigns and extend the current model for pathogen strain
      replacement, which assumes that pathogen strain replacement occurs only through
      the differential effectiveness of vaccines against different pathogen strains.
      Based on a recent theoretical study, we suggest a broader range of possible
      mechanisms, some of which allow pathogen strain replacement even when vaccines
      are perfect-that is, they protect all vaccinated individuals completely against
      all pathogen strains. We draw an analogy with ecological and evolutionary
      explanations for competitive dominance and coexistence that allow for tradeoffs
      between different competitive and life-history traits.

PMID- 17459814
TI  - Privacy and equality in diagnostic genetic testing.
AB  - This study aimed to determine the extent to which the principles of privacy and
      equality were observed during diagnostic genetic testing according to views held
      by patients or child patients' parents (n = 106) and by staff (n = 162) from
      three Finnish university hospitals. The data were collected through a structured
      questionnaire and analysed using the SAS 8.1 statistical software. In general,
      the two principles were observed relatively satisfactorily in clinical practice.
      According to patients/parents, equality in the post-analytic phase and, according
      to staff, privacy in the pre-analytic phase, involved the greatest ethical
      problems. The two groups differed in their views concerning pre-analytic privacy.
      Although there were no major problems regarding the two principles, the
      differences between the testing phases require further clarification. To enhance
      privacy protection and equality, professionals need to be given more
      genetics/ethics training, and patients individual counselling by genetics units
      staff, giving more consideration to patients' world-view, the purpose of the test
      and the test result.

PMID- 17459815
TI  - Differences in moral judgment between nursing students and qualified nurses.
AB  - This longitudinal study examined how nursing students' moral judgment changes
      after they become qualified nurses working in a hospital environment. The sample
      used was a group of 80 nursing students attending a university in Suwon, Korea,
      between 2001 and 2003. By using a Korean version of the Judgment About Nursing
      Decisions questionnaire, an instrument used in nursing care research, moral
      judgment scores based on Ketefian's six nursing dilemmas were determined. The
      results were as follows: (1) the qualified nurses had significantly higher
      idealistic moral judgment scores than the nursing students; (2) the qualified
      nurses showed significantly higher realistic moral judgment scores than the
      nursing students; and (3) when comparing idealistic and realistic moral judgment
      scores, both the qualified nurses and the nursing students had higher scores for
      idealistic moral judgment. Further study is recommended to examine changes in
      moral judgment.

PMID- 17459816
TI  - Moral judgement competence and moral attitudes of medical students.
AB  - A cross-sectional study explored the moral judgement competence and moral
      attitudes of 310 Czech and Slovak and 70 foreign national students at the Medical
      Faculty of Charles University in Hradec Kralove, Czech Republic. Lind's Moral
      Judgement Test was used to evaluate moral judgement competence and moral
      attitudes depending on factors such as age, number of semesters of study, sex,
      nationality and religion. Moral judgement competence decreased significantly in
      the Czech and Slovak medical students as they grew older; in medical students
      from other countries it did not significantly increase. The influence of other
      factors (sex, nationality and religion) on moral judgement competence was not
      proven in either the Czech and Slovak or the foreign national medical students.
      Moral attitudes do not change; the Czech and Slovak as well as the foreign
      students preferred the post-conventional levels of moral judgement (Kohlberg's
      5th and 6th stages). The fact that the Czech and Slovak students' moral judgement
      competence decreased with age and number of semesters of study completed is not
      an optimistic sign: medical students who had undergone a lower number of
      semesters of study were morally more competent.

PMID- 17459817
TI  - Perceptions of conscience in relation to stress of conscience.
AB  - Every day situations arising in health care contain ethical issues influencing
      care providers' conscience. How and to what extent conscience is influenced may
      differ according to how conscience is perceived. This study aimed to explore the
      relationship between perceptions of conscience and stress of conscience among
      care providers working in municipal housing for elderly people. A total of 166
      care providers were approached, of which 146 (50 registered nurses and 96 nurses'
      aides/enrolled nurses) completed a questionnaire containing the Perceptions of
      Conscience Questionnaire and the Stress of Conscience Questionnaire. A
      multivariate canonical correlation analysis was conducted. The first two
      functions emerging from the analysis themselves explained a noteworthy amount of
      the shared variance (25.6% and 17.8%). These two dimensions of the relationship
      were interpreted either as having to deaden one's conscience relating to external
      demands in order to be able to collaborate with coworkers, or as having to deaden
      one's conscience relating to internal demands in order to uphold one's identity
      as a 'good' health care professional.

PMID- 17459818
TI  - Exploring the moral distress of registered nurses.
AB  - Registered nurses (RNs) employed in an urban medical center in the USA identified
      moral distress as a practice concern. This study describes RNs' moral distress
      and the frequency of morally distressing events. Data were collected using the
      Moral Distress Scale and an open-ended questionnaire. The instruments were
      distributed to direct-care-providing RNs; 100 responses were returned. Morally
      distressing events included: working with staffing levels perceived as 'unsafe',
      following families' wishes for patient care even though the nurse disagreed with
      the plan, and continuing life support for patients owing to family wishes despite
      patients' poor prognoses. One high frequency distressing event was carrying out
      orders for unnecessary tests and treatments. Qualitative data analysis revealed
      that the nurses sought support and information from nurse managers, chaplaincy
      services and colleagues. The RNs requested further information on biomedical
      ethics, suggested ethics rounds, and requested a non-punitive environment
      surrounding the initiation of ethics committee consultations.

PMID- 17459819
TI  - The respectful nurse.
AB  - Respect is much referred to in professional codes, in health policy documents and
      in everyday conversation. What respect means and what it requires in everyday
      contemporary nursing practice is less than clear. Prescriptions in professional
      codes are insufficient, given the complexity and ambiguity of everyday nursing
      practice. This article explores the meaning and requirements of respect in
      relation to nursing practice. Fundamentally, respect is concerned with value:
      where ethical value or worth is present, respect is indicated. Raz has argued
      that the two ways of encountering value are to respect and to engage with it. The
      former requires acknowledgement and preservation. Respect in nursing practice
      necessarily requires also engagement. Respect is an active value and can be
      conceptualized within the context of virtue ethics as a hybrid virtue having both
      intellectual and ethical components. Examples from the literature are provided to
      illustrate situations where the respectful nurse requires these components or
      capabilities.

PMID- 17459820
TI  - The 'little extra' that alleviates suffering.
AB  - Nursing, or caring science, is mainly concerned with developing knowledge of what
      constitutes ideal, good health care for patients as whole persons, and how to
      achieve this. The aim of this study was to find clinical empirical indications of
      good ethical care and to investigate the substance of ideal nursing care in
      praxis. A hermeneutic method was employed in this clinical study, assuming the
      theoretical perspective of caritative caring and ethics of the understanding of
      life. The data consisted of two Socratic dialogues: one with nurses and one with
      nursing students, and interviews with two former patients. The empirical data are
      first described from a phenomenological approach. Observations of caregivers
      offering 'the little extra' were taken to confirm that patients were 'being
      seen', not from the perspective of an ideal nursing model, but from that of
      interaction as a fellow human being. The study provides clinical evidence that,
      as an ontological response to suffering, 'symbolic acts' such as giving the
      'little extra' may work to bridge gaps in human interaction. The fact that
      'little things' have the power to preserve dignity and make patients feel they
      are valued offers hope. Witnessing benevolent acts also paves the way for both
      patients and caregivers to increase their understanding of life.

PMID- 17459821
TI  - Clinical wisdom among proficient nurses.
AB  - This article examines clinical wisdom, which has emerged from a broader study
      about nurse managers' influence on proficient registered nurse turnover and
      retention. The purpose of the study was to increase understanding of proficient
      nurses' experience and clinical practice by giving voice to the nurses
      themselves, and to look for differences in their practice. This was a qualitative
      study based on semistructured interviews followed by analysis founded on
      Gadamerian hermeneutics. The article describes how proficient nurses experience
      their practice. Proficient practice constitutes clinical wisdom based on
      responsibility, thinking and ethical discernment, and a drive for action. The
      study showed that poor working conditions cause proficient nurses to regress to
      non-proficient performance. Further studies are recommended to allow deeper
      searching into the area of working conditions and their relationship to lack of
      nurse proficiency.

PMID- 17459822
TI  - Older people's reasoning about age-related prioritization in health care.
AB  - The aim of this study was to describe the reasoning of people aged 60 years and
      over about prioritization in health care with regard to age and willingness to
      pay. Healthy people (n = 300) and people receiving continuous care and services
      (n = 146) who were between 60 and 101 years old were interviewed about their
      views on prioritization in health care. The transcribed interviews were analysed
      using manifest and latent qualitative content analysis. The participants'
      reasoning on prioritization embraced eight categories: feeling secure and
      confident in the health care system; being old means low priority; prioritization
      causes worries; using underhand means in order to be prioritized; prioritization
      as a necessity; being averse to anyone having precedence over others; having
      doubts about the distribution of resources; and buying treatment requires wealth.

PMID- 17459823
TI  - Experiences of self-determination by older persons living in sheltered housing.
AB  - Respect for autonomy and self-determination is a central principle in nursing
      ethics. Autonomy and quality of life are strongly connected, and, at the same
      time, autonomy is an important quality indicator on how older persons' housing
      functions. In this study, autonomy was conceived as self-determination. The aim
      of the study was to describe how older people living in sheltered housing
      experience self-determination and how they are valued as human beings. Eleven
      persons living in five different housing facilities for older people in southern
      Sweden were interviewed. The data were analysed by manifest and latent
      qualitative content analysis. The overall theme expressing the latent content in
      the interviews emerged as disempowerment, which implied an environment that does
      not strengthen individual self-determination. The results showed a negative
      experience of how these older people thought they were valued in the sheltered
      housing where they lived. In sheltered housing, more attention should be paid to
      residents' self-determination and sense of value.

PMID- 17459824
TI  - Publishing in English-language journals.
AB  - The need for academics to get their work published can be fraught with problems,
      especially if they have to publish in the English language and within western
      culture, both of which may be unfamiliar to them. Before considering a
      submission, authors need to satisfy the rigors of their studies: suitability of
      the subject matter for a particular journal; concepts, literature and
      instruments; and if the English is adequate. These are issues of responsibility
      of authors to readers and, on the part of editors and reviewers, to authors and
      through them to students and readers of the submitted texts. This short article
      elaborates on these themes by detailing specific items of importance.

PMID- 17459826
TI  - Atypical scrapie in a Swiss goat and implications for transmissible spongiform
      encephalopathy surveillance.
AB  - Different types of transmissible spongiform encephalopathies (TSEs) affect sheep
      and goats. In addition to the classical form of scrapie, both species are
      susceptible to experimental infections with the bovine spongiform encephalopathy
      (BSE) agent, and in recent years atypical scrapie cases have been reported in
      sheep from different European countries. Atypical scrapie in sheep is
      characterized by distinct histopathologic lesions and molecular characteristics
      of the abnormal scrapie prion protein (PrP(sc)). Characteristics of atypical
      scrapie have not yet been described in detail in goats. A goat presenting
      features of atypical scrapie was identified in Switzerland. Although there was no
      difference between the molecular characteristics of PrP(sc) in this animal and
      those of atypical scrapie in sheep, differences in the distribution of
      histopathologic lesions and PrP(sc) deposition were observed. In particular the
      cerebellar cortex, a major site of PrP(sc) deposition in atypical scrapie in
      sheep, was found to be virtually unaffected in this goat. In contrast, severe
      lesions and PrP(sc) deposition were detected in more rostral brain structures,
      such as thalamus and midbrain. Two TSE screening tests and PrP(sc)
      immunohistochemistry were either negative or barely positive when applied to
      cerebellum and obex tissues, the target samples for TSE surveillance in sheep and
      goats. These findings suggest that such cases may have been missed in the past
      and could be overlooked in the future if sampling and testing procedures are not
      adapted. The epidemiological and veterinary public health implications of these
      atypical cases, however, are not yet known.

PMID- 17459827
TI  - Performance of a foot-and-mouth disease virus reverse transcription-polymerase
      chain reaction with amplification controls between three real-time instruments.
AB  - The foot-and-mouth disease virus (FMDV) is a member of the picornavirus family,
      possessing an 8-kb single-stranded RNA genome of positive polarity. It is highly
      contagious among several livestock species and can lead to severe economic
      consequences, as evidenced by the UK outbreak in 2001. The usage of real-time
      polymerase chain reaction has facilitated rapid detection of FMDV. Several real
      time PCR instruments are available with various capabilities, such as portability
      and high sample volume analysis. Primers and a dual-labeled TaqMan probe were
      optimized to detect a single, highly conserved 88-bp segment of the FMDV 3D (RNA
      polymerase) gene. To increase the confidence of the RT-PCR result, a positive
      amplification control was synthesized to detect potential false-positive results
      due to contamination if a wild-type virus is used as positive control. In
      addition, a preventative measure against false-negative results was developed in
      which endogenous beta actin mRNA is coamplified by RT-PCR. Assay performance was
      compared on the LightCycler1.2 (Roche), the SmartCyclerII (Cepheid), and the SDS
      7900HT (ABI). These assays successfully identified the FMDV genome and beta actin
      mRNA from several sources of infected nasal and oral swabs, as well as probang
      samples.

PMID- 17459828
TI  - Development and application of an enzyme-linked immunosorbent assay for detection
      of bovine viral diarrhea antibody based on Erns glycoprotein expressed in a
      baculovirus system.
AB  - The BVDV envelope glycoprotein E(rns)/gp48 and the C terminal 79 amino acids of
      the capsid protein coding region were expressed in a baculovirus system and
      antigenically characterized. Western blot assay was used to detect recombinant
      E(rns) (r-E(rns)) in infected insect cells using specific monoclonal antibodies.
      The r-E(rns) was then used in an indirect ELISA to detect BVDV specific
      antibodies in a panel of 540 well-characterized sera. Results of the r-E(rns)
      ELISA were compared to those obtained with a commercially available competitive
      ELISA targeting anti-NS2/3 antibodies. A good correlation was observed between
      the 2 ELISA (kappa = 0.916, 95% C.I.: 0.876, 0.956). Using the commercial NS2/3
      ELISA as the reference test, the relative sensitivity of r-E(rns) ELISA was 97.5%
      (95% C.I.: 94.3%, 99.1%) and the relative specificity was 93.9% (95% C.I.: 89.4%,
      96.9%), while relative specificity was 100% (95% C.I.: 97%, 100%) using true
      negative sera (derived from a negative herd). All but 1 antigen positive animals
      (n = 36) tested negative in the r-E(rns) ELISA; among them all 22 confirmed PI
      animals were negative by r-E(rns) ELISA. The ability of r-E(rns) ELISA to
      identify cattle immunized with inactivated vaccine was also demonstrated in a
      small group of cattle, compared to an NS2/3 antibody ELISA. Results suggest that
      r-E(rns) ELISA represents an alternative test for antibody generated by natural
      infection or BVDV vaccination.

PMID- 17459829
TI  - Comparison of five diagnostic methods for detecting bovine viral diarrhea virus
      infection in calves.
AB  - Five diagnostic techniques performed on skin biopsies (shoulder region) and/or
      serum were compared for detection of bovine viral diarrhea virus infection in 224
      calves 0-3 months of age, 23 calves older than 3 months but younger than 7
      months, and 11 cattle older than 7 months. The diagnostic methods used were
      immunohistochemistry (IHC), 2 commercial antigen ELISAs, 1 commercial antibody
      ELISA, and real-time RT-PCR. Results of 249 out of 258 skin and serum samples
      were identical and correlated within the 3 antigen detection methods and the real
      time RT-PCR used. Twenty-six of these 249 samples were BVDV-positive with all
      antigen detection methods and the real-time RT-PCR. Nine out of 258 samples
      yielding discordant results were additionally examined by RT-PCR, RT-PCR
      Reamplification (ReA), and antigen ELISA I on serum and by immunohistochemistry
      on formalin fixed and paraffin-embedded skin biopsies. Virus isolation and
      genotyping was performed as well on these discordant samples. In 3 cases,
      transiently infected animals were identified. Two samples positive by real-time
      RT-PCR were interpreted as false positive and were ascribed to cross
      contamination. The antigen ELISA II failed to detect 2 BVDV-positive calves due
      to the presence of maternal antibodies; the cause of 2 false-positive cases in
      this ELISA remained undetermined. Only persistently infected animals were
      identified in skin samples by IHC or antigen ELISA I. The 3 antigen detection
      methods and the real-time RT-PCR used in parallel had a high correlation rate
      (96.5%) and similar sensitivity and specificity values.

PMID- 17459830
TI  - Detection of infectious bursal disease virus from formalin-fixed paraffin
      embedded tissue by immunohistochemistry and real-time reverse transcription
      polymerase chain reaction.
AB  - Formalin fixed paraffin embedded tissues blocks are used routinely to diagnose
      the economically important immunosuppressive infectious bursal disease virus
      (IBDV) in chickens. Immunohistochemical detection of viruses in tissue blocks has
      been done with varying results between laboratories. Extraction of IBDV RNA from
      tissue blocks allows IBDV strain identification at a molecular level. This allows
      correlation between virus identity and histological lesions present in the
      tissue. Experimentally reverse transcription-polymerase chain reaction (RT-PCR)
      detectable IBDV RNA could always be extracted from tissue blocks with acute +3 or
      higher histological lesion scores. However, many blocks from diagnostic field
      cases did not yield detectable IBDV RNA, in spite of having severe IBDV
      histological lesion scores. The reason for this can be the effect different
      formalin fixation conditions have on RNA detection from tissue blocks. To study
      the effect of various fixation parameters on RNA extraction and
      immunohistochemical detection of IBDV, bursas with maximum histological lesion
      score of 4 for IBDV were fixed in formalin under various conditions (different pH
      levels, temperatures, concentrations of formalin, and fixation duration). Only
      tissues fixed in formalin with a pH of 7.0, concentration of 5 or 10%
      formaldehyde, storage temperature of 25 degrees C or less, and kept for up to 2
      weeks in formalin yielded detectable IBDV RNA upon extraction. No RNA could be
      detected from tissues fixed under extreme temperature, pH, or formalin
      concentrations. Optimal fixation conditions for IHC detection of IBDV were 10%
      formalin concentration, pH 7.0, and temperature of 4 degrees C, where maximum
      intensity of immunostaining was observed.

PMID- 17459831
TI  - Augmentation of secreted and intracellular gamma interferon following johnin
      purified protein derivative sensitization of cows naturally infected with
      Mycobacterium avium subsp. paratuberculosis.
AB  - Measurement of secreted interferon (IFN)-gamma has proven to be a valuable tool
      for the detection of animals infected with mycobacterial pathogens, including
      Mycobacterium avium subsp. paratuberculosis. Previous reports have suggested that
      tuberculin skin testing can influence the performance of the IFN-gamma assay. In
      the present study, healthy noninfected cows, and cows subclinically and
      clinically infected with M. paratuberculosis were administered an intradermal
      injection of johnin purified protein derivative (JPPD) and effects on secreted
      and intracellular IFN-gamma were observed. Intradermal injection resulted in
      significant increases in secreted IFN-gamma for subclinically infected cows after
      stimulation of peripheral blood mononuclear cells (PBMC) with concanavalin A or
      M. paratuberculosis antigen preparations (whole-cell sonicate and JPPD) on days 7
      and 10 postinjection. Intracellular IFN-gamma was increased after intradermal
      injection in total PBMC for all treatment groups and was higher within CD4+ and
      CD8+ subpopulations for infected cows compared to healthy controls throughout the
      study. When T-cell populations were further defined by CD45RO expression,
      intracellular IFN-gamma was higher within CD8+/CD45RO+ lymphocytes compared to
      CD4+/CD45RO+ cells for subclinically and clinically infected cows but similar
      within these subpopulations for healthy controls. These results indicate that
      intradermal sensitization of cows in the subclinical stage of infection will
      upregulate expression of IFN-gamma, enhancing the sensitivity of this assay. In
      addition, CD8+ lymphocytes appear to play an important role as a mediator of M.
      paratuberculosis infection in naturally exposed cattle.

PMID- 17459832
TI  - A prospective, case control study evaluating the association between Clostridium
      difficile toxins in the colon of neonatal swine and gross and microscopic
      lesions.
AB  - Clostridium difficile infection in swine has most often been described in
      suckling pigs, where it has been associated with mesocolonic edema and
      typhlocolitis. This prospective study was designed to assess the correlation
      between the presence of C. difficile toxins (TCd) in the colon contents of
      neonatal pigs and a number of parameters, including gross evidence of diarrhea,
      mesocoloninc edema, typhlitis, and colitis. C. difficile was isolated from 51%
      (66/129) of large intestines and TCd was detected in the colon contents of 50%
      (65/129) of the piglets. Fifty-eight percent (38/65) of TCd-positive piglets had
      normal to pelleted colon and rectal contents, whereas 75% (48/64) of TCd-negative
      pigs had gross evidence of diarrhea. Clostridium difficile toxin-positive animals
      were significantly more likely to have normal to pelleted feces. Edema of the
      mesocolon was observed in 38/65 (59%) of TCd-positive piglets. Because a high
      number of TCd-positive piglets (41%) lacked edema of the mesocolon and a high
      number of TCd-negative pigs had mesocolonic edema (51%), a statistically
      significant association between TCd and mesocolonic edema was not identified.
      Seventy-five percent (49/65) of TCd-positive piglets had colitis and 47/65 (72%)
      had typhlitis. The association between TCd and both colitis and typhlitis was
      statistically significant. Apparently healthy piglets were obtained from 5
      separate sites. Because TCd was detected in the colon contents of 23/29 (79%)
      apparently healthy piglets obtained from 5 separate sites, and 70% of TCd
      positive control pigs had colitis, C. difficile may represent an important
      subclinical issue in neonatal swine.

PMID- 17459833
TI  - Epidemiological investigation of the prevalence and features of postweaning
      multisystemic wasting syndrome in Japan.
AB  - To investigate the prevalence and features of postweaning multisystemic wasting
      syndrome (PMWS) in Japan, an epidemiological study was conducted in 692 weaned
      pigs with various clinical signs, commonly including wasting or weight loss,
      collected from 129 swine farms between 2000 and 2003. The presence of PMWS was
      diagnosed by the detection of characteristic histological lesions and moderate to
      large amounts of porcine circovirus type 2 (PCV2) antigen within the lesions in
      multiple lymphoid tissues. Postweaning multisystemic wasting syndrome was
      positive in 23.4% of pigs (162/692) over the course of the study, and occurred in
      50.4% of the farms (65/129). Mortality in 30-120-day-old pigs in the farms
      positive for PMWS varied from 0.1 to 32.0%. No significant difference in
      mortality was seen between PMWS-positive and -negative farms (P = 0.1). However,
      mortality was significantly higher in the PMWS-positive farms where PMWS was
      diagnosed in more than 50% of the pigs examined compared to farms negative for
      PMWS (P = 0.02). These findings indicate that PMWS has spread widely in Japan.
      Moreover it may exist in variable forms in swine farms, including an epidemic
      form or a subtle endemic or sporadic form. A case-control study suggested that
      risk factors for the occurrence of PMWS include porcine reproductive and
      respiratory syndrome (PRRS) pneumonias and Mycoplasma hyorhinis infection.

PMID- 17459834
TI  - Development of a real-time polymerase chain reaction assay for rapid diagnosis of
      neuropathogenic strains of equine herpesvirus-1.
AB  - This communication reports the development and performance assessment of a rapid
      diagnostic test for identifying horses actively infected with the neurovirulent
      pathotype of equine herpesvirus-1 (EHV-1). The test is a real-time polymerase
      chain reaction (PCR)-based assay that uses EHV-1 pathotype-specific TaqMan(R)
      reporter probes for discrimination between neuropathogenic and non
      neuropathogenic strains of EHV-1 in equine blood or nasal swabs. The diagnostic
      performance of the new technique was evaluated by testing specimens collected
      from 234 horses involved in recent outbreaks of EHV-1 myeloencephalopathy at
      three separate thoroughbred racetracks and one large riding/boarding stable. Side
      by-side comparison of the EHV-1 pathotyping results yielded by the new single
      step, PCR-based allelic discrimination technique (24-hour turn-around-time) with
      those generated by a multi-step, conventional nested PCR followed by nucleotide
      sequencing of the amplified DNA (4-day turn-around-time) revealed complete
      agreement between the 2 test methods. The ability to rapidly identify horses
      infected with neuropathogenic strains of EHV-1 using a single-step, PCR-based
      method has significant implications for future diagnostic evaluation of suspect
      animals.

PMID- 17459835
TI  - Development of an assay to determine single nucleotide polymorphisms in the prion
      gene for the genetic diagnosis of relative susceptibility to classical scrapie in
      sheep.
AB  - The objective of this study was to develop a reliable Taqman 5' Nuclease Assay
      for genotyping sheep for scrapie susceptibility. The sheep prion gene contains 2
      single nucleotide polymorphisms (SNPs) that may mediate resistance to classical
      scrapie, one at codon 136, alanine (A) or valine (V), and another at codon 171,
      arginine (R) or glutamine (Q). The R allele appears to confer resistance to
      classical scrapie, with the AA(136) RR(171) genotype the most resistant to
      scrapie and QR(171) only rarely infected in the US sheep population. The Assays
      by Design protocol was used for development of probes and primers for codon 136
      and Primer Express for codon 171. Commercially available kits were used to
      isolate genomic DNA from blood or muscle. For validation, 70 SNP determinations
      for each codon were compared to commercial testing with an error rate of less
      than 1%. Then, 935 samples from blood (n = 818) and muscle (n = 117) were tested
      for both codons with 928 successful determinations and only 7 samples (<1% of
      total samples) that needed repeating. Genotypes were AA QQ (n = 102; 11.0%), AV
      QQ (n = 28; 3.0%), AA QR (n = 396; 42.7%), AV QR (n = 54; 5.8%), and AA RR (n =
      348; 37.5%). Thus, 86% of the sheep tested (n = 798) contained R at codon 171 and
      were expected to be scrapie-resistant. This new Taqman 5' Nuclease SNP genotyping
      assay is accurate, easy to perform, and useful in the study of classical scrapie
      in sheep and its prevention through selective breeding programs to eliminate
      highly susceptible animals.

PMID- 17459836
TI  - Genetic characterization of canine rotavirus isolated from a puppy in Korea and
      experimental reproduction of disease.
AB  - Canine rotavirus was isolated from feces of a Korean Jindo dog with mild
      diarrhea, and the isolate was genetically characterized. Rotaviral antigen was
      detected in the feces using a commercial rotavirus antigen detection kit and
      cytopathic effects were observed in a cell line inoculated with the feces. The
      virus isolate (GC/KS05) was identified as subtype G3P[3] using reverse
      transcription polymerase chain reaction (RT-PCR). The strain displayed 98% and
      90% identity with the VP7 genes of a canine rotavirus isolate (RV52/96) from
      Italy and the simian rotavirus strain (RRV) respectively. However, the GC/KS05
      isolate exhibited only 83% and 82% identity, respectively, with the G3 serotype
      canine strains, RV198/95 and K9. Phylogenetic analysis of the VP7 and VP4 genes
      of GC/KS05 strain led to the classification of VP7 in a different cluster than
      other canine rotavirus VP7 genes, and VP4 within the cluster of canine rotavirus
      VP4 genes. The Korean isolate was thus more closely related to the RV52/96
      isolate than the other isolates for which sequence data is available. Detailed
      analysis of the VP7 region revealed 6 amino acid variations between the new
      isolate and RV52/96. After 5 passages in cell culture, the GC/KS05 strain
      remained pathogenic for young pups, in which inoculation resulted in diarrhea and
      virus shedding in the feces.

PMID- 17459837
TI  - Comparative serological study of Leptospira serovar hardjo genotypes for use in
      the microscopic agglutination test.
AB  - A comparative serological study was conducted using the Leptospira microscopic
      agglutination test (MAT). Genotypes hardjoprajitno (HP), hardjo-bovis A (HA), and
      hardjo-bovis B (HB) were compared to determine which best detects hardjo antibody
      in cattle serum. A total of 2,431 cattle sera were tested. Sera were collected
      from 4 geographic regions of the United States. Samples were obtained without
      knowledge of breed, age, vaccination history, or herd health status. Of the sera
      collected, 60.7% (1,475) were negative at the 1 : 100 dilution for all three
      genotypes. Serological reactivity at the 1 : 100 dilution was identified in 956
      (39.3%) of the sera tested. Considering the 956 positive sera, 941 (98.4%)
      reacted to HP, whereas the remaining 15 sera (1.6%) reacted to only HA and/or HB.
      A total of 394/941 (41.9%) HP positive sera failed to react to HA or HB. The
      results of this study support the conclusion that HP antigen was most sensitive
      in detection of hardjo antibody.

PMID- 17459838
TI  - Skin test and gamma interferon enzyme-linked immunosorbent assay results in sheep
      exposed to dead Mycobacterium avium subspecies paratuberculosis organisms.
AB  - Cell-mediated immunity (CMI) diagnostic tests, such as the gamma interferon
      enzyme-linked immunosorbent assay (IFN-gamma ELISA) and the Johnin skin test,
      have the potential to detect animals infected with Mycobacterium avium subspecies
      paratuberculosis (MAP) early in the course of the disease. While these CMI tests
      tend to be relatively specific in noninfected flocks, in MAP-infected flocks,
      these tests often identify animals that cannot be confirmed infected by any other
      reference test, including necropsy and culture. The aim of this study was to
      determine if antigen exposure by inhalation or oral ingestion of killed MAP
      organisms would cause a detectable CMI response in sheep. Forty-eight lambs 4
      months of age were randomly divided into a control group, an orally exposed group
      (dosed with 1 x 10(10) autoclaved MAP organisms 3 times), and an inhalation
      exposed group (dosed once with 1 x 10(5) dead organisms). Lambs were skin tested
      and/or bled pre-exposure and 1, 2, 3, 4, and 12 months postexposure. No
      significant difference was seen with either the oral- or inhalation-exposed
      groups of lambs versus controls with either the IFN-gamma ELISA or the skin test
      at any time pre- or postexposure. These results suggest that infection/invasion
      of MAP organisms must occur in order to have a positive skin test or IFN-gamma
      ELISA beyond the false-positive rate. Simple exposure is not enough to elicit a
      detectable CMI response.

PMID- 17459839
TI  - Application and field validation of a PCR assay for the detection of Mycoplasma
      hyopneumoniae from swine lung tissue samples.
AB  - A PCR assay was validated for the detection of Mycoplasma hyopneumoniae in
      porcine lung tissue. The detection limit of the assay was 0.18 colony-forming
      units/g of lung sample spiked with M. hyopneumoniae. In field validation, 426
      pigs from 220 cases were examined for M. hyopneumoniae infection by M.
      hyopneumoniae PCR and a fluorescent antibody (FA) test. In total, 103 pig lungs
      (24.2%) were positive in the PCR test, and 69 pig lungs (16.2%) were positive in
      the FA test, among which, 62 pigs were positive for both PCR and FA test. Most of
      the PCR-positive but FA test-negative cases had lesions compatible with M.
      hyopneumoniae infection. With Bayesian modeling, the diagnostic sensitivity and
      specificity of the PCR were determined to be 97.3% and 93.0%, respectively.

PMID- 17459840
TI  - Detection of pathogens in ovine and caprine abortion samples from Sardinia,
      Italy, by PCR.
AB  - During 2003-2005, 399 abortion samples (315 fetuses and 84 placentae) were
      collected from 107 ovine and caprine farms in northern Sardinia. Tissues from
      aborted fetuses and placentae were examined by PCR assay to detect DNA from
      Coxiella burnetii, Chlamydophila abortus, Salmonella enterica Serovar
      abortusovis, Toxoplasma gondii, and Neospora caninum. The DNA from at least 1 of
      these 5 infectious agents was amplified in 41% of ovine fetuses, while only 17%
      of the caprine fetuses yielded a positive amplification result for at least 1 of
      the 5 agents. Out of a total of 366 ovine aborted samples, T. gondii DNA was
      detected most frequently (18.1% of fetuses and 13.1% of placentae), followed by
      S. abortusovis (13% of fetuses and 14.4% of placentae), C. burnetii (10.9% of
      fetuses, of 9.2% placentae), C. abortus (2.4% of fetuses, 6.5% of placentae), and
      N. caninum (2% of placentae). In 33 fetuses and 9 placentae, the simultaneous
      presence of pathogens with different associations was detected. Out of a total of
      31 caprine aborted samples, T. gondii was detected most frequently (13% of
      fetuses and 25% of placentae), followed by C. abortus (12.5% of placentae), C.
      burnetii (12.5% of placentae), and N. caninum (8.6%).

PMID- 17459841
TI  - Diagnosis of paratuberculosis by fecal culture and ELISA on milk and serum
      samples in two types of Chilean dairy goat herds.
AB  - Fecal culture has been the primary method used to diagnose paratuberculosis in
      goats. It is laborious, slow, and expensive. Validation of enzyme-linked
      immunosorbent assays (ELISAs) on milk samples could make paratuberculosis testing
      more widely available for goat farmers. The aim of this study was to determine
      the accuracy of serum and milk ELISAs for paratuberculosis, relative to fecal
      culture, in Chilean dairy goats. Eight dairy goat herds were selected. Feces,
      blood, and milk samples were collected from all female goats >2 years old. Fecal
      samples were cultured using Herrold egg yolk medium with mycobactin J and
      antibiotics. Serum and milk samples were tested using a commercial ELISA kit for
      Mycobacterium avium subsp. paratuberculosis antibody detection. A total of 383
      goats were tested by ELISA and fecal culture. The sensitivity of ELISA on serum
      and milk relative to fecal culture was 74.3% (95% CI: 59.8-88.8) and 60% (95% CI:
      43.8-76.2), respectively. The corresponding values for ELISA specificity based on
      the percentage of non- M. avium subsp. paratuberculosis-infected goats testing
      ELISA-negative were 98.6% (95% CI: 96.6-100) and 99.3% (95% CI: 97.9-100) on
      serum and milk, respectively. Proportions of positive results for serum and fecal
      samples were significantly different, whereas the proportions of positive results
      for milk and fecal samples were not significantly different. The milk ELISA had a
      moderate level of agreement with fecal culture results (Kappa = 0.57). The
      paratuberculosis ELISA on goat milk samples may be a cost-effective, accurate
      alternative to fecal culture.

PMID- 17459842
TI  - Use of a polymerase chain reaction for detection of Mycoplasma dispar in the
      nasal mucus of calves.
AB  - A polymerase chain reaction (PCR) assay was developed for the detection of
      Mycoplasma dispar in nasal mucus samples collected from calves. The target DNA
      sequence was the 16S rRNA gene, and the fragment was selected within a region of
      high polymorphism. The specificity and detection limit of the method were
      determined. This method was then used for the detection of M. dispar in nasal
      swabs collected from 301 calves, including 155 clinical samples from animals
      showing signs of respiratory disease and 146 samples from healthy animals. PCR
      with generic primers was applied to the detection of Mollicutes, followed by the
      detection of M. dispar. Mollicutes were detected in 52.05% of clinical samples
      from healthy animals and in 90.96% of samples from sick animals. Mycoplasma
      dispar was detected in 6.16% of healthy animals and in 34.84% of sick animals.
      The PCR assay was useful in verifying the presence of M. dispar in calves and may
      be a useful tool in monitoring this mycoplasma in cattle herds.

PMID- 17459843
TI  - Bovine cardiac troponin T is not accurately quantified with a common human
      clinical immunoassay.
AB  - The detection of myocardial injury in cattle caused by the ingestion of
      cardiotoxic compounds or cardiac diseases would be facilitated by the
      availability of a rapid and specific quantitative serum assay for cardiac
      troponins. Therefore, the accuracy of the only cardiac troponin T (cTnT)
      immunoassay to receive approval by the US Food and Drug Administration for the
      measurement of cTnT in human serum was evaluated to quantify the protein in
      bovine serum. Recovery experiments were performed by the addition of purified
      bovine cTnT to normal bovine serum. Cardiac troponin T was quantified using an
      immunoassay commonly used for the measurement of cTnT in human serum. The
      immunoassay demonstrated a well correlated (r = 0.99) and linear dose-dependent
      response to bovine cTnT but with poor accuracy (slope = 0.024; 95% CI = 0.018 to
      0.030). The mean recovery of bovine cTnT was 2.4% across a concentration range of
      10 ng/ml to 1,000 ng/ml. These studies demonstrate that a commonly used
      immunoassay for the measurement of cTnT in human serum demonstrates poor accuracy
      for the quantification of bovine cTnT.

PMID- 17459844
TI  - Brain lesions in pigs affected with postweaning multisystemic wasting syndrome.
AB  - Anti-porcine circovirus type 2 (anti-PCV2) immunostaining was associated with
      cerebellar lymphohistiocytic vasculitis combined with hemorrhages (50 pigs) or
      with lymphohistiocytic meningitis (23 pigs) in pigs naturally affected with
      postweaning multisystemic wasting syndrome (PMWS). The animals originated from 12
      farms in Rio Grande do Sul, Brazil. In total, 456 unthrifty 3- to 5-month-old
      postweaning pigs confirmed as PMWS cases were necropsied. Although most findings
      mimicked those extensively reported in PMWS-affected pigs, there were distinctive
      brain lesions that included multiple hemorrhages in the cerebellar leptomeninges
      associated with lymphohistiocytic vasculitis and fibrinoid degeneration in
      vessels of the cerebellum and periventricular areas (69 pigs). These vascular
      lesions were also seen in conjunction with lymphohistiocytic meningitis (38
      additional pigs). PCV2 antigen was immunohistochemically demonstrated in the
      cytoplasm and nuclei from intralesional perivascular macrophages and endothelial
      like cells in brain tissues. Together these findings suggest that these lesions
      were caused by PCV2.

PMID- 17459845
TI  - Necrotizing encephalitis of unknown cause in Fennoscandian Arctic foxes (Alopex
      lagopus).
AB  - A neurologic disease affected a colony of endangered Fennoscandian arctic foxes
      (Alopex lagopus) kept in captivity for breeding purposes. Several outbreaks of
      disease occurred between 1994 and 2004. The clinical signs included ataxia,
      indications of anosmia, blindness, and abnormal behavior. The disease was
      characterized by severe necrotizing encephalitis affecting mostly the cranial
      cerebrum, basal ganglia, and olfactory bulbs. Investigations to identify the
      etiology of the disease included testing for several infectious agents known to
      cause encephalitis in carnivores. Tests for Toxoplasma gondii, Encephalitozoon
      cuniculi, Neospora caninum, canine distemper virus, rabies, adenovirus type 1,
      Borna disease virus, and Listeria monocytogenes were negative. The colony was
      closed, and the cause of the disease remains undetermined.

PMID- 17459846
TI  - Abomasal coccidiosis associated with proliferative abomasitis in a sheep.
AB  - Abomasal coccidiosis was diagnosed in an 11-month-old female sheep that died
      after a 2-week period of anorexia and diarrhea. The abomasal mucosa was grossly
      thickened with a nodular surface and focal areas of hemorrhage. Microscopically,
      the middle to deep abomasal mucosa contained many intact and ruptured giant
      protozoal schizonts associated with hyperplasia of mucous neck cells, parietal
      cell atrophy, moderate lymphocytic-plasmacytic inflammation, and fibrosis
      centered on mineralized remnants of degenerate schizont walls. Sexual tissue
      stages and oocysts were not present. Microscopic features of schizonts and
      ultrastuctural features of merozoites were comparable to previous descriptions of
      Eimeria (Globidium) gilruthi, a coccidian of uncertain taxonomic status
      historically associated with incidental infections of the abomasum in sheep and
      goats. The distinctive lesions suggest that, similar to ostertagiasis, heavy
      coccidial infection of the abomasum should be considered as a cause of anorexia,
      diarrhea, and proliferative abomasitis in sheep.

PMID- 17459847
TI  - Atypical coccidiosis in South American camelids.
AB  - Reported clinical signs of coccidiosis in South American camelids include
      anorexia of a few days duration, sudden death, and diarrhea. Antemortem diagnosis
      of clinical coccidiosis is usually based on clinical signs and supported by
      detection of coccidial oocysts in feces. This report describes 2 atypical cases
      of coccidiosis in South American camelids that had no coccidial oocysts detected
      on antemortem fecal flotation, prolonged weight loss, and normal fecal
      consistency.

PMID- 17459848
TI  - Accidental intra-auricular artery injection of ceftiofur in two beef steers.
AB  - Two beef steers accidentally injected into a branch of the auricular artery with
      an oil-based formulation of ceftiofur died within 5 minutes of injection. Notable
      pathologic findings included distention and obstruction of cerebral and
      cerebellar arteries by a whitish tan material and hemorrhages within meningeal
      spaces, the choroid plexus, cerebrum, and cerebellum. Lipid material was
      identified within cerebral blood vessels in frozen sections stained with oil red
      O. This report describes an unusual case of brain ischemia in beef cattle.

PMID- 17459849
TI  - Hypertrichosis in a horse with alimentary T-cell lymphoma and pituitary
      involvement.
AB  - A 13-year-old Quarterhorse mare had a 6-month history of diarrhea, progressive
      weight loss, and lethargy. At presentation the mare was hirsute, had
      hyperhidrosis, and abnormal fat distribution in addition to severe diarrhea. A
      presumptive clinical diagnosis of protein-losing enteropathy and pituitary pars
      intermedia dysfunction was made. T-cell lymphoma was diagnosed in a rectal biopsy
      specimen. The owner elected to euthanize the mare because of poor prognosis and
      the severity of the disease. At necropsy, the mare had hypertrichosis and the
      pituitary gland was diffusely enlarged. Histologically, neoplastic lymphocytes
      infiltrated the gastrointestinal mucosa, mesenteric lymph nodes, and the
      pituitary gland. In addition, there was hyperplasia of the pituitary gland pars
      intermedia. Pituitary adenoma was not present. Hypertrichosis in this case could
      have been triggered by a combination of adenomatous hyperplasia of pars
      intermedia and lymphoma resulting in disruption of the hypothalamic dopaminergic
      tone or disruption of the hypothalamic thermoregulatory center.

PMID- 17459850
TI  - Diagnostic characterization of a feral swine herd enzootically infected with
      Brucella.
AB  - Eighty feral swine were trapped from a herd that had been documented to be
      seropositive for Brucella and which had been used for Brucella abortus RB51
      vaccine trials on a 7,100-hectare tract of land in South Carolina. The animals
      were euthanized and complete necropsies were performed. Samples were taken for
      histopathology, Brucella culture, and Brucella serology. Brucella was cultured
      from 62 (77.5%) animals. Brucella suis was isolated from 55 animals (68.8%), and
      all isolates were biovar 1. Brucella abortus was isolated from 28 animals
      (35.0%), and isolates included field strain biovar 1 (21 animals; 26.3%), vaccine
      strain Brucella abortus S19 (8 animals, 10.0%), and vaccine strain Brucella
      abortus RB51 (6 animals, 7.5%). Males were significantly more likely to be
      culture positive than females (92.9% vs. 60.6%). Thirty-nine animals (48.8%) were
      seropositive. Males also had a significantly higher seropositivity rate than
      females (61.9% vs. 34.2%). The relative sensitivity rates were significantly
      higher for the standard tube test (44.6%) and fluorescence polarization assay
      (42.6%) than the card agglutination test (13.1%). Lesions consistent with
      Brucella infection were commonly found in the animals surveyed and included
      inflammatory lesions of the lymph nodes, liver, kidney, and male reproductive
      organs, which ranged from lymphoplasmacytic to pyogranulomatous with necrosis.
      This is the first report of an apparent enzootic Brucella abortus infection in a
      feral swine herd suggesting that feral swine may serve as a reservoir of
      infection for Brucella abortus as well as Brucella suis for domestic livestock.

PMID- 17459851
TI  - Development of a 1-step enzyme-linked immunosorbent assay for the rapid diagnosis
      of bovine respiratory syncytial virus in postmortem specimens.
AB  - Bovine respiratory syncytial virus (BRSV) is associated with severe respiratory
      disease in cattle. BRSV infection frequently leads to the death of young infected
      animals. The presence of BRSV in postmortem specimens is routinely detected using
      indirect immunofluorescence (IIF). However, this technique requires special
      equipment and considerable expertise. The present paper describes the development
      of a 1-step ELISA for rapid (1.5 hours) detection of BRSV antigen in organ
      homogenates. The performance of the new 1-step ELISA was evaluated using bovine
      postmortem specimens (n = 108) in comparison with 3 other BRSV diagnostic
      techniques: indirect immunofluorescence, the Clearview respiratory syncytial
      virus (RSV) test, and real-time reverse transcriptase polymerase chain reaction
      (RT-PCR). The relative sensitivity, specificity, and the kappa coefficient of 1
      step ELISA, the Clearview RSV electroimmunoassay (EIA), and IIF were calculated,
      using real-time RT-PCR as the reference test. The new 1-step ELISA was the most
      sensitive and specific of the 3 tests. Thus, the new 1-step ELISA is a reliable
      test for detecting BRSV antigen in organ homogenates.

PMID- 17459852
TI  - An indirect enzyme-linked immunosorbent assay for detection of antibodies to
      Actinobacillus pleuropneumoniae serovar 7 in pig serum.
AB  - Lipopolysaccharide (LPS) antigen was purified from Actinobacillus
      pleuropneumoniae serovar 7 by phenol-water extraction and fractionated on a, S
      100 Sephacryl column. High molecular weight fractions of LPS purified from the S
      100 column were pooled and used as antigen in an indirect serovar 7 ELISA. The
      ELISA was evaluated with sera from pigs experimentally infected with 11 different
      A. pleuropneumoniae serovars of biotype 1. Estimation of sensitivity and
      specificity of the A. pleuropneumoniae serovar 7 ELISA was performed using pig
      sera from herds naturally infected with A. pleuropneumoniae serovar 7 as well as
      sera from herds free of infection with A. pleuropneumoniae serovar 7. When
      compared to the complement fixation test (CFT) as a reference test, the ELISA
      showed much higher sensitivity and statistically equivalent specificity.

PMID- 17459853
TI  - Detection of mixed infections with "Candidatus Mycoplasma haemominutum" and
      Mycoplasma haemofelis using real-time TaqMan polymerase chain reaction.
AB  - The objective of this study was to evaluate the use of real-time TaqMan PCR
      assays for detection of coinfections with "Candidatus Mycoplasma haemominutum"
      (Mhm), and Mycoplasma haemofelis (Mhf), in vitro and over time in experimentally
      infected cats. First, the ability of each real-time PCR assay to detect and
      quantify mixed infections was determined in vitro by testing mixtures of plasmids
      containing Mhm and Mhf 16S rDNA with each assay. Subsequently, 4 specific
      pathogen-free (SPF) cats, 2 of which were splenectomized, were inoculated with
      blood from a cat infected with both Mhm and Mhf. Sixteen blood samples were then
      collected from each cat over a 55-day period. Each of the 64 postinoculation
      samples was tested using both conventional polymerase chain reaction (cPCR) and
      real-time PCR for the 16S rRNA gene of each organism. When applied to mixtures of
      plasmid DNA from each species, the results of quantitation with each of the real
      time PCR assays approximately reflected the number of plasmid copies present.
      Forty-nine of 64 post-inoculation samples (77%) were positive using both cPCR and
      real-time PCR, 4 (6%) were positive using cPCR only, and 3 (5%) were positive
      using real-time PCR only. Both organisms were detected in 23 samples using real
      time PCR. Mixed infections were not detected using cPCR. The size of the
      corresponding cPCR products suggested infection with Mhm in 4 and Mhf in 18 of
      these samples. The use of multiple separate real-time PCR assays rather than cPCR
      alone should thus be considered for epidemiologic studies of hemoplasmosis in
      cats.

PMID- 17459854
TI  - Growth and metabolic characterization of Macrorhabdus ornithogaster.
AB  - Macrorhabdus ornithogaster (M. ornithogaster) is an anamorphic ascomycetous yeast
      found only in the stomach of birds. Infection is often benign but has also been
      associated with disease in some species of birds under some circumstances. In
      vitro efforts to grow M. ornithogaster have been largely unsuccessful. In this
      report, multiple liquid and solid media of varying pH, sugar concentration, and
      fetal bovine serum (FBS) concentrations, incubated at various temperatures in
      room air or microaerophilic conditions, were examined for their ability to
      support the growth of M. ornithogaster, obtained from a budgerigar (Melopsittacus
      undulatus). Optimum growth conditions were found to be Basal Medium Eagle's, pH 3
      to 4, containing 20% FBS, and 5% glucose or sucrose under microaerophilic
      conditions at 42 degrees C. Using these conditions, M. ornithogaster was
      repeatedly passaged without loss of viability. Polyclonal isolates of M.
      ornithogaster consistently assimilated glucose, sucrose, and trehalose. M.
      ornithogaster did not grow with prolonged exposure to atmospheric oxygen, but
      growth in microaerophilic conditions was moderately enhanced by preincubation
      with atmospheric oxygen for 24 hours. An isolate of M. ornithogaster was found to
      be infective to day-old chickens, reduce their rate of weight gain, and induce a
      mild to moderate heterophilic inflammation of the isthmus. M. ornithogaster was
      reisolated from the chicks 7 days after infection, fulfilling Koch's postulates.
      A 761-bp sequence of 18S rDNA from this isolate was compared to the originally
      reported M. ornithogaster sequence and was found to be 97% identical.

PMID- 17459855
TI  - Critical assessment of the diagnostic value of feline alpha1-acid glycoprotein
      for feline infectious peritonitis using the likelihood ratios approach.
AB  - Alpha-1-acid glycoprotein (AGP) increases in the blood of cats with feline
      infectious peritonitis (FIP), a lethal disease caused by feline coronavirus
      (FCoV). However, the diagnostic potential of AGP might be limited because AGP
      also increases in pathophysiological conditions other than FIP. In this
      retrospective study, the diagnostic potential of serum AGP concentration was
      evaluated on the basis of the pretest probability of disease, according to the
      Bayesian approach. Serum AGP levels from cats with FIP (group 1; n = 58) and
      without FIP (group 2; n = 104) were evaluated. Non-FIP cats were further
      subgrouped as follows: 2a) inflammation (n = 26), 2b) asymptomatic FCoV infection
      (n = 49), 2c) injection-site sarcoma (n = 19), 2d) postvaccination (n = 7), and
      2e) specific pathogen free (n = 3). Standard descriptive analyses by group and
      empirical receiver-operating characteristic (ROC) curve estimation were
      performed. Ordinary logistic regression analysis was performed to derive an
      estimate of the continuous likelihood ratio to produce the posttest probability
      of disease for any combination of pretest probability and serum AGP value. The
      comparison of serum AGP levels in the different groups and the analysis of the
      ROC curve confirmed that serum AGP is a powerful discriminating marker for FIP.
      The Bayesian approach demonstrated that when the pretest probability of FIP is
      high, based on history and clinical signs (groups 1 or 2a), moderate serum AGP
      levels (1.5-2 mg/ml) can discriminate cats with FIP from others, while only high
      serum AGP levels (>3 mg/ml) can support a diagnosis of FIP in cats with a low
      pretest probability of disease (groups 2b to 2e).

PMID- 17459856
TI  - Characterization of rupture of abdominal artery aneurysm in dairy cattle.
AB  - In this retrospective study, the authors describe the gross and histologic
      changes associated with rupture of an abdominal artery aneurysm in 33 mature
      female Holstein cattle between January 1980 and June 2005 from 29 farms in
      upstate New York and northern Pennsylvania. Over this period, there was an
      increase in the number of cases submitted for necropsy per year, and a seasonal
      trend did not exist. Affected animals ranged from 2.5 to 5.5 years of age.
      Grossly affected cattle exhibited marked hemoabdomen. There was marked dilation
      and rupture of the abdominal aorta or one of its branches, including the
      mesenteric, left gastric, celiac artery, right ruminal artery, or left ruminal
      artery. Histologically, the tunica media of the affected arteries was often thin
      and irregular in width with disrupted, fragmented, and coiled elastin.
      Granulation tissue and hemorrhage was localized at the site of rupture. There was
      mild-to-marked hyperplasia of the tunica intima that was irregular and disorderly
      with adjacent smooth-muscle hyperplasia within the tunica media. In addition, in
      a fraction of cases, there was mild-to-moderate mucinous change (48%) and
      mineralization (30%) within the tunica media. To the authors' knowledge, this is
      the first description of the gross and histologic changes in Holstein cows with
      abdominal artery aneurysm and rupture.

PMID- 17459857
TI  - Genetic evidence for multi-event imports of avian influenza virus A (H5N1) into
      Bavaria, Germany.
AB  - The almost simultaneous initial detections of avian influenza A H5N1 viruses in
      central Europe in February 2006, at a time devoid of migratory bird activity,
      raised the question of the origin of these viruses. This report presents
      molecular data from Europe providing evidence for multiple and spatially
      overlapping H5N1 introductions into Bavaria, Germany.

PMID- 17459858
TI  - In situ hybridization for Lawsonia intracellularis--specific 16s rRNA sequence in
      paraffin-embedded tissue using a digoxigenin-labeled oligonucleotide probe.
AB  - An in situ hybridization (ISH) procedure with a digoxigenin-labeled
      oligonucleotide probe for detection of Lawsonia intracellularis in paraffin
      embedded tissue is described. This technique recognized 71% of PCR-positive cases
      and was thus superior to Warthin-Starry silver stain, which only detected 41%.
      The presented ISH is of comparable sensitivity to previously published
      immunohistochemical assays and is recommended for laboratories wishing to
      diagnose L. intracellularis infections in tissue sections but without access to
      antibodies.

PMID- 17459859
TI  - Effects of blood contamination of cerebrospinal fluid on results of indirect
      fluorescent antibody tests for detection of antibodies against Sarcocystis
      neurona and Neospora hughesi.
AB  - The purpose of this study was to determine the effect of blood contamination of
      cerebrospinal fluid (CSF) on the results of indirect fluorescent antibody tests
      (IFATs) for Sarcocystis neurona and Neospora hughesi. The in vitro study used
      antibody-negative CSF collected from non-neurologic horses immediately after
      euthanasia and blood samples from 40 healthy horses that had a range of IFAT
      antibody titers against S. neurona and N. hughesi. Serial dilutions of whole
      blood were made in seronegative CSF to generate blood-contaminated CSF with red
      blood cell (RBC) concentrations ranging from 10 to 100,000 RBCs/microl. The blood
      contaminated CSF samples were then tested for antibodies against both pathogens
      using IFAT. Blood contamination of CSF had no detectable effect on IFAT results
      for S. neurona or N. hughesi at any serologic titer when the RBC concentration in
      CSF was <10,000 RBCs/microl. At concentrations of 10,000-100,000 RBCs/microl of
      CSF, positive CSF results (IFAT titer >or=5) for S. neurona and N. hughesi were
      detected only when the corresponding serum titers were >or=160 and >or=80,
      respectively. The IFAT performed on CSF is reliable for testing horses for equine
      protozoal myeloencephalitis caused by S. neurona or N. hughesi, even when blood
      contamination causes the RBC concentration in CSF to be up to 10,000 RBCs/microl.

PMID- 17459860
TI  - Investigation of the molecular detection of vaccine-derived equine herpesvirus
      type 1 in blood and nasal secretions from horses following intramuscular
      vaccination.
AB  - The objective of this study was to investigate whether intramuscular vaccination
      of healthy adult horses with a killed or a modified live equine herpesvirus type
      1 (EHV-1) vaccine could induce transient positive PCR results in either blood or
      secretions collected on a nasopharyngeal swab. Four horses in each group received
      either a single killed or a modified-live vaccine intramuscularly. Two local
      commingled and 2 distant nonvaccinated controls were included for each group. All
      horses were observed daily for evidence of clinical abnormalities throughout the
      study periods. Blood and nasopharyngeal swabs were collected twice before
      vaccination and once weekly for 4 weeks after vaccination and submitted for PCR
      testing for EHV-1 by 2 independent laboratories using different real-time PCR
      methodologies. Serum samples collected from all horses on the vaccination day and
      21 days later were tested for antibodies against EHV-1 using a serum
      neutralization test. Whereas the 2 vaccine strains tested positive in both EHV-1
      PCR assays, nasopharyngeal swabs and whole blood collected from vaccinated and
      control horses had negative PCR test results for EHV-1 during the entire study
      period. Serum neutralization testing revealed a 2- to 4-fold increase in titers
      for all vaccinated horses, whereas titers in control horses were largely
      unchanged. The use of seropositive horses before immunization and the sampling
      frequency of 7 days may have prevented the occasional molecular detection of the
      vaccine virus in whole blood and nasopharyngeal secretions. However, the study
      results demonstrate that detection of EHV-1 DNA by PCR in vaccinated and
      unvaccinated healthy horses is not a common event.

PMID- 17459861
TI  - Microalbuminuria and comparison of serologic testing for exposure to Borrelia
      burgdorferi in nonclinical Labrador and Golden Retrievers.
AB  - Canine Lyme disease is caused by the spirochete Borrelia burgdorferi after
      transmission by an Ixodes tick, typically resulting in joint pain, fever and
      lethargy. Lyme nephritis is a poorly characterized syndrome associated with
      severe glomerular and tubular renal injury and poor clinical outcome in young to
      middle-aged dogs positive for exposure to B. burgdorferi. The aims of this study
      were to identify associations between natural exposure to B. burgdorferi and the
      presence of microalbuminuria in nonclinical young Labrador and Golden Retrievers
      and to compare two commonly used serologic tests available to document B.
      burgdorferi exposure: the Western blot and the commercial point-of-care C6
      peptide enzyme-linked immunosorbent assay (ELISA) tests. Microalbuminuria was
      assessed using a commercial point-of-care ELISA specific for canine albumin.
      Blood and urine samples from 268 asymptomatic Labrador and Golden Retrievers were
      included. Of these, 18.7% were positive for B. burgdorferi exposure according to
      the C6 ELISA; 21.2% were positive for natural exposure to B. burgdorferi and
      11.5% for vaccinal antibodies according to the Western blot. The agreement rate
      was 93% between the two tests (kappa = 0.78, P < 0.0001) for natural exposure.
      Urine from 6.1% of the dogs was positive for microalbuminuria. There was no
      association between microalbuminuria and exposure to B. burgdorferi based on
      results of a Western blot (P = 0.57) or C6 ELISA (P = 0.53). Microalbuminuria is
      likely not a consequence of B. burgdorferi exposure in young nonclinical Labrador
      and Golden Retrievers.

PMID- 17459862
TI  - Failure to detect bovine viral diarrhea virus in necropsied farm-raised white
      tailed deer (Odocoileus virginianus) in Pennsylvania.
AB  - Between January 1 and December 31, 2005 gross and histologic examinations were
      performed on carcasses of 61 farm-raised white-tailed deer originating from
      Pennsylvania. Single-tube real-time reverse transcription polymerase chain
      reaction (real-time RT-PCR) for the detection of bovine viral diarrhea virus type
      1 (BVDV-1) and type 2 (BVDV-2) was performed on each animal. Virus isolation was
      performed on tissue samples from 25 of 61 animals. Immunohistochemical (IHC)
      staining of ear-notch skin to identify BVDV antigen was performed on each animal.
      All tissues samples tested negative for both BVDV-1 and BVDV-2 by real-time RT
      PCR, virus isolation, and IHC. Gross or histopathologic lesions suggestive of
      BVDV infection were not detected. Results of this study suggest that BVD is not a
      common cause of mortality in farm-raised white-tailed deer in Pennsylvania.

PMID- 17459863
TI  - Superoxide dismutase expression and oxidative damage in a case of myopathy in
      brown pelicans (Pelecanus occidentalis).
AB  - Four brown pelicans (Pelecanus occidentalis) housed at a rehabilitation facility
      were found dead after a 3-day history of muscle weakness and after being fed for
      about 2 weeks from a recent shipment of fish. The birds had pale streaking of the
      skeletal and heart muscles. Microscopically, the skeletal muscle, and to a lesser
      extent the cardiac muscle, had severe myocyte degeneration and necrosis
      characterized by microvacuolation with loss of cross-striations, condensation of
      cytoplasm, fragmentation, mineralization, and inflammatory cell infiltrates
      consisting of multinucleated cells, macrophages, and few heterophils. The
      findings were consistent with myopathy, and a nutritional myopathy caused by
      eating rancid fish was suspected. Immunohistochemical staining revealed abundant
      immunoreactive copper zinc superoxide dismutase and manganese superoxide
      dismutase either as diffuse homogeneous precipitates or granular aggregates in
      the cytoplasm of affected cells. Immunoreactivity was directly related to degree
      of cellular damage as estimated by light microscopic examination. We suggest that
      the lack of protection, despite upregulation of superoxide dismutase, is most
      likely attributable to supersaturation of oxidants beyond the capacity of
      superoxide dismutases to scavenge.

PMID- 17459864
TI  - Sodium fluoride/copper naphthenate toxicosis in cattle.
AB  - Fourteen cattle on a Kansas pasture died from ingestion of a wood preservative
      compound containing sodium fluoride and copper naphthenate. Clinical signs
      included depression, anorexia, ataxia, diarrhea, and recumbency. Grossly visible
      lesions included perirenal edema, pale kidneys, and forestomach ulceration. All 3
      cows that had postmortem evaluations had extensive renal cortical tubular
      necrosis. Tissue concentrations of fluoride were slightly elevated above expected
      background levels, while copper tissue concentrations were not elevated. The
      findings indicated that the sodium fluoride caused renal tubular necrosis leading
      to renal failure. Copper naphthenate may have contributed to abomasal ulceration;
      however, tissue copper concentrations indicated that copper from the formulation
      was not appreciably absorbed from the gastrointestinal tract.

PMID- 17459865
TI  - Polypoid uterine leiomyosarcomas in a sheep.
AB  - Leiomyosarcoma was diagnosed in the uterus surgically removed from a 3-year-old
      pet Suffolk ewe with a history of bleeding from the vulva, spontaneous lactation,
      and nursing behavior. The uterus contained multiple well-circumscribed, soft,
      intraluminal polypoid masses of variable sizes (0.5-4 cm). The masses were red,
      with white, smooth, and glistening cut surfaces. Histologically they comprised
      variably dense sheets of moderately pleomorphic, plump spindle cells embedded in
      richly vascularized stroma. The mitotic index was usually low (0-1/high-power
      field), but in some polyps there were up to 10 mitoses/high-power field.
      Neoplastic cells stained positive for alpha smooth muscle actin (alpha-SMA) by
      immunohistochemistry. Ultrastructural features of neoplastic cells included the
      presence of basal lamina, scant microfilaments, contracted nuclei with blunt
      ends, and flat intercellular junctions. Uterine leiomyosarcoma was diagnosed
      based on cellular morphology and atypia and positive immunohistochemistry for
      alpha-SMA.

PMID- 17459866
TI  - Diagnosis of Amanita toxicosis in a dog with acute hepatic necrosis.
AB  - Poisoning with amanitin-containing hepatotoxic mushrooms demands extensive
      efforts from clinicians, toxicologists, and pathologists. Presumptive diagnoses
      are established by positive identification of the suspect mushroom along with the
      occurrence of consistent clinical signs. If the animal dies, hepatic lesions may
      suggest exposure to amanitin-containing mushrooms; however, lesions are
      nonspecific. A 15-week-old female Dachshund was presented to the referring
      veterinarian for acute onset of lethargy that quickly progressed to sternal
      recumbency. Despite supportive care, the dog remained lethargic and died
      approximately 12 hours after initial presentation. A pale tan liver was noted at
      necropsy. Microscopically, the liver showed panlobular coagulative necrosis of
      hepatocytes. A presumptive diagnosis of amanitin poisoning was based on suspect
      history of exposure to mushrooms, clinical signs, and pathologic findings.
      Exposure to amanitin was confirmed through detection of alpha-amanitin in the
      liver by liquid chromatography/mass spectrometry. The objective of this case
      report is to illustrate the essential components to a successful diagnostic work
      up of a suspect case of hepatotoxic mushroom poisoning. Although hepatotoxic
      mushroom poisoning has been documented in dogs before, confirmatory techniques
      for biologic specimens have not been used previously in diagnostic
      investigations.

PMID- 17459868
TI  - Congenital lobar emphysema and tension pneumothorax in a dog.
AB  - Congenital lobar emphysema (CLE) and tension pneumothorax (TPT) are rarely
      reported in dogs. A case of CLE of the right middle lung lobe predisposing to air
      trapping, alveolar hyperinflation, and pleural rupture resulting in fatal
      spontaneous TPT in a 6-month-old mixed breed dog is described. The unique
      alteration of "bloat line" was observed in this case in addition to compressive
      atelectasis of all other lung lobes and lack of negative pressure within the
      thoracic cavity, signifying markedly elevated intrathoracic pressure. Bronchial
      cartilage hypoplasia and bronchiectasis were confirmed microscopically, which
      likely led to abnormal dynamic collapse of bronchi during expiration,
      consequentially leading to increased intrapulmonary pressure, bullous emphysema,
      and pleural rupture resulting in TPT. TPT consequent to CLE may therefore be
      considered one of the potential causes of sudden death in young dogs without
      overt clinical illness.

PMID- 17459867
TI  - Infections caused by pathogenic free-living amebas (Balamuthia mandrillaris and
      Acanthamoeba sp.) in horses.
AB  - This article describes amebic infections in 4 horses: granulomatous amebic
      encephalitis caused by Balamuthia mandrillaris and Acanthamoeba culbertsoni and
      systemic infections caused by Acanthamoeba sp. The former infection occurred in 1
      of 4 horses spontaneously without any underlying conditions; the latter amebic
      infection was perhaps "opportunistic" considering the visceral involvement by
      this protozoan in association with Aspergillus sp. and/or Escherichia coli and
      Pseudomonas sp. The clinicopathologic findings and demonstration of the amebic
      organisms using immunohistochemical techniques, culture, polymerase chain
      reactions, and electron microscopy are presented.

PMID- 17459869
TI  - Systemic nocardiosis in a reindeer (Rangifer tarandus tarandus).
AB  - Systemic infection by Nocardia asteroides was diagnosed in a reindeer (Rangifer
      tarandus tarandus). At necropsy, the animal had enlarged tracheobronchial lymph
      nodes, pleural and peritoneal effusions, and numerous, multifocal to coalescing,
      yellow, firm nodules with inspissated pus in the lung, pleura, omentum, liver,
      heart, adrenal glands, and left kidney. Microscopically, the nodules consisted of
      foci of pyogranulomatous inflammation. Microscopic lesions were present in the
      grossly affected organs as well as spleen and brain. Sections stained with Gram
      and modified Fite-Faraco histochemical stains had numerous gram-positive,
      variably acid fast, beaded and branching filamentous organisms in the necrotic
      centers. N. asteroides was isolated from the lung, bronchial lymph nodes, liver,
      and left kidney. To the authors' knowledge, this is the first report of systemic
      N. asteroides infection in a reindeer.

PMID- 17459870
TI  - Toxinotypes of Clostridium perfringens isolated from sick and healthy avian
      species.
AB  - Currently, the factors/toxins responsible for Clostridium perfringens-associated
      avian enteritis are not well understood. To assess whether specific C.
      perfringens' toxinotypes are associated with avian enteritis, the isolates of C.
      perfringens from 31 cases of avian necrotic or ulcerative enteritis submitted
      between 1997 and 2005 were selected for retrospective analysis using multiplex
      PCR. C. perfringens was isolated from chickens, turkeys, quail, and psittacines.
      The toxinotypes of isolates from diseased birds were compared against the
      toxinotype of 19 C. perfringens isolates from avian cases with no evidence of
      clostridial enteritis. All C. perfringens isolates were classified as type A
      regardless of species or disease history. Although many isolates (from all avian
      groups) had the gene encoding the C. perfirngens beta2 toxin, only 54% produced
      the toxin in vitro when measured using Western blot analysis. Surprisingly, a
      large number of healthy birds (90%) carried CPB2-producing isolates, whereas over
      half of the cpb2-positive isolates from diseased birds failed to produce CPB2.
      These data from this investigation do not suggest a causal relationship between
      beta2 toxin and necrotic enteritis in birds.

PMID- 17459871
TI  - Mortality in Pennsylvania captive elk (Cervus elaphus): 1998-2006.
AB  - The necropsy records of 65 elk ranging from 1 day to 13(1/2) years of age were
      reviewed to determine the primary cause of death of each animal. The animal
      carcasses were submitted from 22 separate Pennsylvania elk farms over an
      approximately 8-year period. The most common causes of mortality in animals in
      which the cause of death was determined were gastrointestinal parasitism (21
      cases), pneumonia (7 cases), enterocolitis (5 cases), malnutrition (5 cases), and
      rumenitis/acidosis (5 cases). The cause of death was undetermined in 4 of the 65
      elk. Nematode organisms (20 cases) were the primary parasites identified in cases
      of mortality owing to gastrointestinal parasitism. Arcanobacterium pyogenes (3
      cases), Escherichia coli (3 cases), and Streptococcus sp. (2 cases) were the most
      commonly isolated bacteria from the lung in the cases of pneumonia. Fungal
      organisms, consistent with Aspergillus sp. were present histologically within the
      pulmonary lesions in 5 cases. Bacterial agents associated with enterocolitis
      included Clostridium perfringens (2 cases), E. coli (1 case), Salmonella Newport
      (1 case) and Salmonella Thompson (1 case). The majority (56.3%) of the death loss
      in elk of known ages occurred in animals 1 year of age or less, with 71.4% of the
      gastrointestinal parasitism, 60.0% of the malnutrition, 60.0% of the
      enterocolitis, and 57.1% of the pneumonia cases occurring in animals within this
      age range. In conclusion, gastrointestinal parasitism, pneumonia, malnutrition,
      enterocolitis and rumenitis/acidosis were considered the most common causes of
      death in captive elk in this study.

PMID- 17459872
TI  - The x-ray structure of dTDP-4-keto-6-deoxy-D-glucose-3,4-ketoisomerase.
AB  - The repeating unit of the glycan chain in the S-layer of the bacterium
      Aneurinibacillus thermoaerophilus L420-91(T) is composed of four alpha-d-rhamnose
      molecules and two 3-acetamido-3,6-dideoxy-alpha-d-galactose moieties (abbreviated
      as Fucp3NAc). Formation of the glycan layer requires nucleotide-activated sugars
      as the donor molecules. Whereas the enzymes involved in the synthesis of GDP
      rhamnose have been well characterized, less is known regarding the structures and
      enzymatic mechanisms of the enzymes required for the production of dTDP-Fucp3NAc.
      One of the enzymes involved in the biosynthesis of dTDP-Fucp3NAc is a 3,4
      ketoisomerase, hereafter referred to as FdtA. Here we describe the first three
      dimensional structure of this sugar isomerase complexed with dTDP and solved to
      1.5 A resolution. The FdtA dimer assumes an almost jellyfish-like appearance with
      the sole alpha-helices representing the tentacles. Formation of the FdtA dimer
      represents a classical example of domain swapping whereby beta-strands 2 and 3
      from one subunit form part of a beta-sheet in the second subunit. The active site
      architecture of FdtA is characterized by a cluster of three histidine residues,
      two of which, His(49) and His(51), appear to be strictly conserved in the amino
      acid sequences deposited to date. Site-directed mutagenesis experiments,
      enzymatic assays, and x-ray crystallographic analyses suggest that His(49)
      functions as an active site base.

PMID- 17459873
TI  - Structural basis of the catalytic reaction mechanism of novel 1,2-alpha-L
      fucosidase from Bifidobacterium bifidum.
AB  - 1,2-alpha-L-fucosidase (AfcA), which hydrolyzes the glycosidic linkage of
      Fucalpha1-2Gal via an inverting mechanism, was recently isolated from
      Bifidobacterium bifidum and classified as the first member of the novel glycoside
      hydrolase family 95. To better understand the molecular mechanism of this enzyme,
      we determined the x-ray crystal structures of the AfcA catalytic (Fuc) domain in
      unliganded and complexed forms with deoxyfuconojirimycin (inhibitor), 2'
      fucosyllactose (substrate), and L-fucose and lactose (products) at 1.12-2.10 A
      resolution. The AfcA Fuc domain is composed of four regions, an N-terminal beta
      region, a helical linker, an (alpha/alpha)6 helical barrel domain, and a C
      terminal beta region, and this arrangement is similar to bacterial
      phosphorylases. In the complex structures, the ligands were buried in the central
      cavity of the helical barrel domain. Structural analyses in combination with
      mutational experiments revealed that the highly conserved Glu566 probably acts as
      a general acid catalyst. However, no carboxylic acid residue is found at the
      appropriate position for a general base catalyst. Instead, a water molecule
      stabilized by Asn423 in the substrate-bound complex is suitably located to
      perform a nucleophilic attack on the C1 atom of L-fucose moiety in 2'
      fucosyllactose, and its location is nearly identical near the O1 atom of beta-L
      fucose in the products-bound complex. Based on these data, we propose and discuss
      a novel catalytic reaction mechanism of AfcA.

PMID- 17459874
TI  - Structures of Staphylococcus aureus D-tagatose-6-phosphate kinase implicate
      domain motions in specificity and mechanism.
AB  - High resolution structures of Staphylococcus aureus d-tagatose-6-phosphate kinase
      (LacC) in two crystal forms are herein reported. The structures define LacC in
      apoform, in binary complexes with ADP or the co-factor analogue AMP-PNP, and in a
      ternary complex with AMP-PNP and D-tagatose-6-phosphate. The tertiary structure
      of the LacC monomer, which is closely related to other members of the pfkB
      subfamily of carbohydrate kinases, is composed of a large alpha/beta core domain
      and a smaller, largely beta "lid." Four extended polypeptide segments connect
      these two domains. Dimerization of LacC occurs via interactions between lid
      domains, which come together to form a beta-clasp structure. Residues from both
      subunits contribute to substrate binding. LacC adopts a closed structure required
      for phosphoryl transfer only when both substrate and co-factor are bound. A
      reaction mechanism similar to that used by other phosphoryl transferases is
      proposed, although unusually, when both substrate and co-factor are bound to the
      enzyme two Mg(2+) ions are observed in the active site. A new motif of amino acid
      sequence conservation common to the pfkB subfamily of carbohydrate kinases is
      identified.

PMID- 17459875
TI  - Energy depletion inhibits phosphatidylinositol 3-kinase/Akt signaling and induces
      apoptosis via AMP-activated protein kinase-dependent phosphorylation of IRS-1 at
      Ser-794.
AB  - Energy depletion activates AMP-activated protein kinase (AMPK) and inhibits cell
      growth via TSC2-dependent suppression of mTORC1 signaling. Long term energy
      depletion also induces apoptosis by mechanisms that are not well understood to
      date. Here we show that AMPK, activated by energy depletion, inhibited cell
      survival by binding to and phosphorylating IRS-1 at Ser-794. Phosphorylation of
      IRS-1 at this site inhibited phosphatidylinositol 3-kinase/Akt signaling,
      suppressed the mitochondrial membrane potential, and promoted apoptosis. Of the
      treatments promoting energy depletion, glucose deprivation, hypoxia, and
      inhibition of ATP synthesis in the mitochondria stimulated phosphorylation of IRS
      1 at Ser-794 via an LKB1/AMPK-dependent manner, whereas oxidative stress and 2
      deoxyglucose stimulated phosphorylation at this site via a Ca2+/calmodulin
      dependent protein kinase kinase beta/AMPK axis. These data define a novel pathway
      that cooperates with other adaptive mechanisms to formulate the cellular response
      to energy depletion.

PMID- 17459876
TI  - Formation and function of flavin anion radical in cryptochrome 1 blue-light
      photoreceptor of monarch butterfly.
AB  - The monarch butterfly (Danaus plexippus) cryptochrome 1 (DpCry1) belongs in the
      class of photosensitive insect cryptochromes. Here we purified DpCry1 expressed
      in a bacterial host and obtained the protein with a stoichiometric amount of the
      flavin cofactor in the two-electron oxidized, FAD(ox), form. Exposure of the
      purified protein to light converts the FAD(ox) to the FAD*(-) flavin anion
      radical by intraprotein electron transfer from a Trp residue in the apoenzyme. To
      test whether this novel photoreduction reaction is part of the DpCry1
      physiological photocycle, we mutated the Trp residue that acts as the ultimate
      electron donor in flavin photoreduction. The mutation, W328F, blocked the
      photoreduction entirely but had no measurable effect on the light-induced
      degradation of DpCry1 in vivo. In light of this finding and the recently
      published action spectrum of this class of Crys, we conclude that DpCry1 and
      similar insect cryptochromes do not contain flavin in the FAD(ox) form in vivo
      and that, most likely, the [see text] photoreduction reaction is not part of the
      insect cryptochrome photoreaction that results in proteolytic degradation of the
      photopigment.

PMID- 17459877
TI  - N-methyl-D-aspartate receptor-dependent regulation of the glutamate transporter
      excitatory amino acid carrier 1.
AB  - The neuronal transporter excitatory amino acid carrier 1 (EAAC1) is enriched in
      perisynaptic regions, where it may regulate synaptic spillover of glutamate. In
      this study we examined potential interactions between EAAC1 and ionotropic
      glutamate receptors. N-Methyl-D-aspartate (NMDA) receptor subunits NR1, NR2A, and
      NR2B, but not the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid
      receptor subunit GluR2, were co-immunoprecipitated with EAAC1 from neuron
      enriched hippocampal cultures. A similar interaction was observed in C6 glioma
      and human embryonic kidney cells after co-transfection with Myc epitope-tagged
      EAAC1 and NMDA receptor subunits. Co-transfection of C6 glioma with the
      combination of NR1 and NR2 subunits dramatically increased (approximately 3-fold)
      the amount of Myc-EAAC1 that can be labeled with a membrane-impermeable
      biotinylating reagent. In hippocampal cultures, brief (5 min), robust (100 microM
      NMDA, 10 microM glycine) activation of the NMDA receptor decreased biotinylated
      EAAC1 to approximately 50% of control levels. This effect was inhibited by an
      NMDA receptor antagonist, intracellular or extracellular calcium chelators, or
      hypertonic sucrose. Glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      propionic acid with cyclothiazide, and thapsigargin mimicked the effects of NMDA.
      These studies suggest that NMDA receptors interact with EAAC1, facilitate cell
      surface expression of EAAC1 under basal conditions, and control internalization
      of EAAC1 upon activation. This NMDA receptor-dependent regulation of EAAC1
      provides a novel mechanism that may shape excitatory signaling during synaptic
      plasticity and/or excitotoxicity.

PMID- 17459878
TI  - CD40-40L signaling in vascular inflammation.
AB  - Ligation of CD40 in circulating cells or in the vessel wall may promote
      mononuclear cell recruitment, participate in the weakening of the plaque, and
      contribute to thrombosis. This process appears to be redox-sensitive, but the
      precise signaling mechanism by which the interaction between CD40L and its
      receptor CD40 mediates inflammatory secretion is unclear. Our previous studies
      have shown that the CD40-CD40L interaction modulates release of reactive oxygen
      species (ROS) and the current findings demonstrate that in endothelial cells
      CD40L dose dependently induces intracellular CD40L and MCP1 release in a redox
      sensitive manner. Pharmacological inhibition of phosphatidylinositol 3-kinase and
      p38 MAPK as well as adenovirus-mediated inactivation of Akt and p38 MAPK
      inhibited CD40L effects on endothelial cells. Akt, in particular, appeared to
      mediate CD40L-induced CD40L synthesis and MCP1 release by endothelial cells in a
      redox sensitive manner via NFkappaB activation. In addition, using confocal
      microscopy, exogenous addition of recombinant CD40L or adenoviral mediated CD40L
      overexpression was found to stimulate nuclear translocation of NFkappaB, which
      was further augmented by Akt overexpression and inhibited by Akt inactivation.
      These data support a mechanism whereby redox-sensitive CD40-CD40L interactions
      induce activation of Akt and p38 MAPK, leading to stimulation of NFkappaB and
      enhanced synthesis of CD40L and MCP1. Increased CD40L and MCP1 may contribute to
      the adherence of CD40-positive cells, such as platelets and monocytes, to the
      vessel wall modulating atherothrombosis.

PMID- 17459879
TI  - Capsular arabinomannans from Mycobacterium avium with morphotype-specific
      structural differences but identical biological activity.
AB  - The capsules of two colony morphotypes of Mycobacterium avium strain 2151 were
      investigated, i.e. the virulent smooth-transparent (SmT1) and the nonvirulent
      smooth-opaque (SmO) types. From both morphotypes we separated a nonacylated
      arabinomannan (AM) from an acylated polysaccharide fraction by affinity
      chromatography, of which the AMs were structurally characterized. The AMs from
      the virulent morphotype, in contrast to that from the nonvirulent form, possessed
      a larger mannan chain and a shorter arabinan chain. Incubation of murine bone
      marrow-derived macrophages and human dendritic cells showed that the acylated
      polysaccharide fractions were potent inducers of tumor necrosis factor-alpha,
      interleukin-12, and interleukin-10 compared with nonacylated AMs, which led to
      only a marginal cytokine release. Further in vitro experiments showed that both
      the acylated polysaccharide fractions and the nonacylated AMs were able to induce
      in vitro anti-tumor cytotoxicity of human peripheral blood mononuclear cells.
      Thus, morphotype-specific structural differences in the capsular AMs of M. avium
      do not correlate with biological activity; however, their acylation is a
      prerequisite for effective stimulation of murine macrophages and human dendritic
      cells.

PMID- 17459880
TI  - Mitotic phosphorylation of the anaphase-promoting complex inhibitory subunit Mnd2
      is necessary for efficient progression through meiosis i.
AB  - The yeast anaphase-promoting complex (APC) subunit Mnd2 is necessary for
      maintaining sister chromatid cohesion in prophase I of meiosis by inhibiting
      premature ubiquitination and subsequent degradation of substrates by the
      APC(Ama1) ubiquitin ligase. In a proteomics screen for post-translational
      modifications on the APC, we discovered that Mnd2 is phosphorylated during
      mitosis in a cell cycle-dependent manner. We identified and characterized the
      sites of mitotic Mnd2 phosphorylation during the cell cycle. Collective mutation
      of Mnd2 phosphorylation sites to alanine had no effect on vegetative growth but a
      striking effect (>85% reduction) on the percentage of tetrad-forming cells
      compared with the wild type strain. Similar to the MND2 deletion strain, cells
      harboring the alanine mutant that did not form spores arrested after premeiotic S
      phase with a single undivided nucleus and low levels of the APC(Ama1) meiotic
      substrate, Clb5, relative to wild type cells. In contrast, collective mutation of
      Mnd2 phosphorylation sites to aspartic acid resulted in partial suppression of
      the sporulation defect. No differences were observed in the binding between each
      Mnd2 isoform and the APC in vitro. However, in vivo, we observed a gradient in
      the abundance of APC-associated Mnd2 in each strain that was proportional to the
      observed differences in sporulation and Clb5 levels. Taken together, these data
      suggest that mitotic phosphorylation of Mnd2 is necessary for APC-mediated
      progression beyond the first meiotic nuclear division.

PMID- 17459881
TI  - Major histocompatibility complex class I-ERp57-tapasin interactions within the
      peptide-loading complex.
AB  - The endoplasmic reticulum-located multimolecular peptide-loading complex
      functions to load optimal peptides onto major histocompatibility complex (MHC)
      class I molecules for presentation to CD8(+) T lymphocytes. Two oxidoreductases,
      ERp57 and protein-disulfide isomerase, are known to be components of the peptide
      loading complex. Within the peptide-loading complex ERp57 is normally found
      disulfide-linked to tapasin, through one of its two thioredoxin-like redox
      motifs. We describe here a novel trimeric complex that disulfide links together
      MHC class I heavy chain, ERp57 and tapasin, and that is found in association with
      the transporter associated with antigen processing peptide transporter. The
      trimeric complex normally represents a small subset of the total ERp57-tapasin
      pool but can be significantly increased by altering intracellular oxidizing
      conditions. Direct mutation of a conserved structural cysteine residue implicates
      an interaction between ERp57 and the MHC class I peptide-binding groove. Taken
      together, our studies demonstrate for the first time that ERp57 directly
      interacts with MHC class I molecules within the peptide-loading complex and
      suggest that ERp57 and protein-disulfide isomerase act in concert to regulate the
      redox status of MHC class I during antigen presentation.

PMID- 17459882
TI  - The effect of hinge mutations on effector binding and domain rotation in
      Escherichia coli D-3-phosphoglycerate dehydrogenase.
AB  - D-3-phosphoglycerate dehydrogenase (EC 1.1.1.95) from Escherichia coli contains
      two Gly-Gly sequences that have been shown previously to have the characteristics
      of hinge regions. One of these, Gly(336)-Gly(337), is found in the loop between
      the substrate binding domain and the regulatory domain. Changing these glycine
      residues to valine affected the sensitivity of the enzyme to inhibition by L
      serine but not the extent of inhibition. The decrease in sensitivity was caused
      primarily by a decrease in the affinity of the enzyme for L-serine. These
      mutations also affected the domain rotation of the subunits in response to L
      serine binding. A major conclusion of this study was that it defines a minimal
      limit on the necessary conformational changes leading to inhibition of enzyme
      activity. That is, some of the conformational differences seen in the native
      enzyme upon L-serine binding are not critical for inhibition, whereas others are
      maintained and may play important roles in inhibition and cooperativity. The
      structure of G336V demonstrates that the minimal effect of L-serine binding
      leading to inhibition of enzyme activity requires a domain rotation of
      approximately only 6 degrees in just two of the four subunits of the enzyme that
      are oriented diagonally across from each other in the tetramer. Moreover the
      structures show that both pairs of Asn190 to Asn190 hydrogen bonds across the
      subunit interfaces are necessary for activity. These observations are consistent
      with the half-the-sites activity, flip-flop mechanism proposed for this and other
      similar enzymes and suggest that the Asn190 hydrogen bonds may function in the
      conformational transition between alternate half-the-site active forms of the
      enzyme.

PMID- 17459883
TI  - Mode of membrane interaction and fusogenic properties of a de novo transmembrane
      model peptide depend on the length of the hydrophobic core.
AB  - Model peptides composed of alanine and leucine residues are often used to mimic
      single helical transmembrane domains. Many studies have been carried out to
      determine how they interact with membranes. However, few studies have
      investigated their lipid-destabilizing effect. We designed three peptides
      designated KALRs containing a hydrophobic stretch of 14, 18, or 22
      alanines/leucines surrounded by charged amino acids. Molecular modeling
      simulations in an implicit membrane model as well as attenuated total reflection
      Fourier transform infrared analyses show that KALR is a good model of a
      transmembrane helix. However, tryptophan fluorescence and attenuated total
      reflection-Fourier transform infrared spectroscopy indicate that the extent of
      binding and insertion into lipids increases with the length of the peptide
      hydrophobic core. Although binding can be directly correlated to peptide
      hydrophobicity, we show that insertion of peptides into a membrane is determined
      by the length of the peptide hydrophobic core. Functional studies were performed
      by measuring the ability of peptides to induce lipid mixing and leakage of
      liposomes. The data reveal that whereas KALR14 does not destabilize liposomal
      membranes, KALR18 and KALR22 induce 40 and 50% of lipid-mixing, and 65 and 80% of
      leakage, respectively. These results indicate that a transmembrane model peptide
      can induce liposome fusion in vitro if it is long enough. The reasons for the
      link between length and fusogenicity are discussed in relation to studies of
      transmembrane domains of viral fusion proteins. We propose that fusogenicity
      depends not only on peptide insertion but also on the ability of peptides to
      destabilize the two leaflets of the liposome membrane.

PMID- 17459884
TI  - Structural basis for type II membrane protein binding by ERM proteins revealed by
      the radixin-neutral endopeptidase 24.11 (NEP) complex.
AB  - ERM (Ezrin/Radixin/Moesin) proteins mediate formation of membrane-associated
      cytoskeletons by simultaneously binding actin filaments and the C-terminal
      cytoplasmic tails of adhesion molecules (type I membrane proteins). ERM proteins
      also bind neutral endopeptidase 24.11 (NEP), a type II membrane protein, even
      though the N-terminal cytoplasmic tail of NEP possesses the opposite peptide
      polarity to that of type I membrane proteins. Here, we determined the crystal
      structure of the radixin FERM (Four point one and ERM) domain complexed with the
      N-terminal NEP cytoplasmic peptide. In the FERM-NEP complex, the amphipathic
      region of the peptide forms a beta strand followed by a hairpin that bind to a
      shallow groove of FERM subdomain C. NEP binding is stabilized by beta-beta
      interactions and docking of the NEP hairpin into the hydrophobic pocket of
      subdomain C. Whereas the binding site of NEP on the FERM domain overlaps with the
      binding site of intercellular adhesion molecule (ICAM)-2, NEP lacks the Motif-1
      sequence conserved in ICAM-2 and related adhesion molecules. The NEP hairpin,
      although lacking the typical inter-chain hydrogen bond but is stabilized by
      hydrogen bonds with the main chain and side chains of subdomain C, directs the C
      terminal basic region of the NEP peptide away from the groove and toward the
      membrane. The overlap of the binding sites on subdomain C for NEP and Motif-1
      adhesion molecules such as CD44 provides the structural basis for the suppression
      of cell adhesion through interaction between NEP and ERM proteins.

PMID- 17459885
TI  - Clinical profile and outcome of conversion disorder in children in a tertiary
      hospital of north India.
AB  - The clinical profile, commonly involved precipitating factors, comorbid
      conditions, treatment options and outcome of conversion disorder in 40 children
      in a tertiary level hospital in North India were studied, retrospectively.
      Majority of the patients were from rural India. Most common presenting symptom
      was psychogenic non-epileptic seizures; depression and anxiety were among the
      commonest comorbid conditions. Precipitating factors were predominantly
      scholastic problems. Treatment option included either psychotherapy only or
      combination of psychotherapy and pharmacotherapy. No significant difference was
      found in terms of outcome between the in-patient and out-patient treatment
      groups. This observation could be cost effective for developing countries like
      India, where the resources are very limited.

PMID- 17459886
TI  - Pan-eukaryote ITS2 homologies revealed by RNA secondary structure.
AB  - For evolutionary comparisons, phylogenetics and evaluation of potential
      interbreeding taxa of a species, various loci have served for animals and plants
      and protistans. One [second internal transcribed spacer (ITS2) of the nuclear
      ribosomal DNA] is highly suitable for all. Its sequence is species specific. It
      has already been used extensively and very successfully for plants and some
      protistans, and a few animals (where historically, the mitochondrial genes have
      dominated species studies). Despite initial impressions that ITS2 is too
      variable, it has proven to provide useful biological information at higher
      taxonomic levels, even across all eukaryotes, thanks to the conserved aspects of
      its transcript secondary structure. The review of all eukaryote groups reveals
      that ITS2 is expandable, but always retains in its RNA transcript a common core
      structure of two helices with hallmark characteristics important for ribosomal
      RNA processing. This aspect of its RNA transcript secondary structure can rescue
      difficult alignment problems, making the ITS2 a more powerful tool for
      phylogenetics. Equally important, the recognition of eukaryote-wide homology
      regions provides extensive and detailed information to test experimental studies
      of ribosomal rRNA processing.

PMID- 17459887
TI  - Amino acid residues of the Escherichia coli tRNA(m5U54)methyltransferase (TrmA)
      critical for stability, covalent binding of tRNA and enzymatic activity.
AB  - The Escherichia coli trmA gene encodes the tRNA(m5U54)methyltransferase, which
      catalyses the formation of m5U54 in tRNA. During the synthesis of m5U54, a
      covalent 62-kDa TrmA-tRNA intermediate is formed between the amino acid C324 of
      the enzyme and the 6-carbon of uracil. We have analysed the formation of this
      TrmA-tRNA intermediate and m5U54 in vivo, using mutants with altered TrmA. We
      show that the amino acids F188, Q190, G220, D299, R302, C324 and E358, conserved
      in the C-terminal catalytic domain of several RNA(m5U)methyltransferases of the
      COG2265 family, are important for the formation of the TrmA-tRNA intermediate
      and/or the enzymatic activity. These amino acids seem to have the same function
      as the ones present in the catalytic domain of RumA, whose structure is known,
      and which catalyses the formation of m5U in position 1939 of E. coli 23 S rRNA.
      We propose that the unusually high in vivo level of the TrmA-tRNA intermediate in
      wild-type cells may be due to a suboptimal cellular concentration of SAM, which
      is required to resolve this intermediate. Our results are consistent with the
      modular evolution of RNA(m5U)methyltransferases, in which the specificity of the
      enzymatic reaction is achieved by combining the conserved catalytic domain with
      different RNA-binding domains.

PMID- 17459888
TI  - Chemical synthesis of a very long oligoribonucleotide with 2-cyanoethoxymethyl
      (CEM) as the 2'-O-protecting group: structural identification and biological
      activity of a synthetic 110mer precursor-microRNA candidate.
AB  - A long RNA oligomer, a 110mer with the sequence of a precursor-microRNA
      candidate, has been chemically synthesized in a single synthesizer run by means
      of standard automated phosphoramidite chemistry. The synthetic method involved
      the use of 2-cyanoethoxymethyl (CEM), a 2'-hydroxyl protecting group recently
      developed in our laboratory. We improved the methodology, introducing better
      coupling and capping conditions. The overall isolated yield of highly pure 110mer
      was 5.5%. Such a yield on a 1-mumol scale corresponds to 1 mg of product and
      emphasizes the practicality of the CEM method for synthesizing oligomers of more
      than 100 nt in sufficient quantity for biological research. We confirmed the
      identity of the 110mer by matrix-assisted laser desorption/ionization time-of
      flight (MALDI-TOF) mass spectrometry, as well as HPLC, electrophoretic methods,
      and RNase-digestion experiments. The 110mer also showed sense-selective specific
      gene-silencing activity. As far as we know, this is the longest chemically
      synthesized RNA oligomer reported to date. Furthermore, the identity of the
      110mer was confirmed by both physicochemical and biological methods.

PMID- 17459890
TI  - An adaptation of the LMS method to determine expression variations in profiling
      data.
AB  - One of the major issues in expression profiling analysis still is to outline
      proper thresholds to determine differential expression, while avoiding false
      positives. The problem being that the variance is inversely proportional to the
      log of signal intensities. Aiming to solve this issue, we describe a model,
      expression variation (EV), based on the LMS method, which allows data
      normalization and to construct confidence bands of gene expression, fitting cubic
      spline curves to the Box-Cox transformation. The confidence bands, fitted to the
      actual variance of the data, include the genes devoid of significant variation,
      and allow, based on the confidence bandwidth, to calculate EVs. Each outlier is
      positioned according to the dispersion space (DS) and a P-value is statistically
      calculated to determine EV. This model results in variance stabilization. Using
      two Affymetrix-generated datasets, the sets of differentially expressed genes
      selected using EV and other classical methods were compared. The analysis
      suggests that EV is more robust on variance stabilization and on selecting
      differential expression from both rare and strongly expressed genes.

PMID- 17459889
TI  - A bona fide La protein is required for embryogenesis in Arabidopsis thaliana.
AB  - Searches in the Arabidopsis thaliana genome using the La motif as query revealed
      the presence of eight La or La-like proteins. Using structural and phylogenetic
      criteria, we identified two putative genuine La proteins (At32 and At79) and
      showed that both are expressed throughout plant development but at different
      levels and under different regulatory conditions. At32, but not At79, restores
      Saccharomyces cerevisiae La nuclear functions in non-coding RNAs biogenesis and
      is able to bind to plant 3'-UUU-OH RNAs. We conclude that these La nuclear
      functions are conserved in Arabidopsis and supported by At32, which we renamed as
      AtLa1. Consistently, AtLa1 is predominantly localized to the plant nucleoplasm
      and was also detected in the nucleolar cavity. The inactivation of AtLa1 in
      Arabidopsis leads to an embryonic-lethal phenotype with deficient embryos
      arrested at early globular stage of development. In addition, mutant embryonic
      cells display a nucleolar hypertrophy suggesting that AtLa1 is required for
      normal ribosome biogenesis. The identification of two distantly related proteins
      with all structural characteristics of genuine La proteins suggests that these
      factors evolved to a certain level of specialization in plants. This
      unprecedented situation provides a unique opportunity to dissect the very
      different aspects of this crucial cellular activity.

PMID- 17459891
TI  - Theoretical study of large conformational transitions in DNA: the B<-->A
      conformational change in water and ethanol/water.
AB  - We explore here the possibility of determining theoretically the free energy
      change associated with large conformational transitions in DNA, like the solvent
      induced B<-->A conformational change. We find that a combination of targeted
      molecular dynamics (tMD) and the weighted histogram analysis method (WHAM) can be
      used to trace this transition in both water and ethanol/water mixture. The
      pathway of the transition in the A-->B direction mirrors the B-->A pathway, and
      is dominated by two processes that occur somewhat independently: local changes in
      sugar puckering and global rearrangements (particularly twist and roll) in the
      structure. The B-->A transition is found to be a quasi-harmonic process, which
      follows closely the first spontaneous deformation mode of B-DNA, showing that a
      physiologically-relevant deformation is in coded in the flexibility pattern of
      DNA.

PMID- 17459892
TI  - Scores of asthma and asthma severity reveal new regions of linkage in EGEA study
      families.
AB  - There is ongoing debate as to how asthma should be defined in order to forward
      understanding of the underlying mechanisms. The aim of the present study was to
      build quantitative scores of asthma and asthma severity and to assess whether
      refinement of disease phenotypes can facilitate the identification of chromosomal
      regions harbouring susceptibility genes. A genome-wide linkage scan was conducted
      in 110 families with at least two asthmatic siblings (n = 508) from the French
      Epidemiological study on the Genetics and Environment of Asthma, bronchial
      hyperresponsiveness and atopy (EGEA). The phenotypes studied were an asthma
      severity score (assessed among asthmatics by combining clinical data and
      treatment), forced expiratory volume in one second (FEV(1)) and an asthma score
      (including both asthmatics and nonasthmatics and representing the whole disease
      spectrum). This analysis showed genome-wide suggestive evidence of linkage of the
      asthma score to 18p11, a novel region undetected in a previous screen of
      dichotomous asthma. There was potential linkage of 2p23 to asthma severity score
      and of three regions (1p36, 2q36 and 6q14) to FEV(1). Moreover, FEV(1) appeared
      to have no genetic determinant in common with asthma severity and asthma scores.
      Asthma and asthma severity quantitative scores revealed new regions of linkage
      and thus provide support for considering these phenotypes in future genetic
      studies.

PMID- 17459893
TI  - Systematic review of noninvasive positive pressure ventilation in severe stable
      COPD.
AB  - The present systematic review examined the effectiveness of bilevel noninvasive
      positive pressure ventilation (NIPPV) in the management of chronic respiratory
      failure (CRF) due to severe stable chronic obstructive pulmonary disease (COPD).
      Randomised controlled trials (RCTs) and non-RCTs (crossover design) of adults
      with severe stable COPD and CRF receiving bilevel NIPPV via nasal, oronasal or
      total face mask were identified from electronic databases and manual screening of
      journals and reference lists. Respiratory function (gas exchange, lung function,
      ventilatory/breathing pattern, respiratory muscle function and work of breathing)
      and health-related outcomes (dyspnoea, functional status, exercise tolerance,
      health-related quality of life (HRQOL), morbidity and mortality) were assessed.
      In total, 15 studies met the inclusion criteria: six RCTs and nine non-RCTs. RCTs
      did not find improved gas exchange with bilevel NIPPV, while non-RCTs did. Lung
      hyperinflation and diaphragmatic work of breathing were reduced in a
      nonrandomised subset. HRQOL and dyspnoea, the least studied outcomes, showed
      improvement with bilevel NIPPV. In a subset of individuals on maximal medical
      treatment regimes for severe stable chronic obstructive pulmonary disease,
      bilevel noninvasive positive pressure ventilation may have an adjunctive role in
      the management of chronic respiratory failure through attenuation of compromised
      respiratory function and improvement in health-related outcomes.

PMID- 17459894
TI  - Peroxisome proliferator-activated receptor expression is reduced in skeletal
      muscle in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a multiorgan systemic disease.
      The systemic features are skeletal muscle weakness and cachexia, the latter being
      associated with systemic inflammation. The exact mechanisms underlying skeletal
      muscle dysfunction in COPD remain obscure. Recent evidence suggests involvement
      of the peroxisome proliferator-activated receptors (PPARs) and PPAR-gamma
      coactivator (PGC)-1alpha in regulation of skeletal muscle morphology and
      metabolism, and mitochondrial transcription factor A (TFAM) has been implicated
      in the process of mitochondrial biogenesis. The aim of the present exploratory
      study was, therefore, to compare these factors in the skeletal muscle of nine
      healthy control subjects and 14 COPD patients stratified by cachexia. PPAR-gamma,
      PPAR-delta and TFAM were measured at the mRNA and protein level by real-time
      quantitative PCR and Western blotting, respectively. PPAR-alpha and PGC-1alpha
      were meansured at the mRNA level. PPAR-delta and TFAM protein content, as well as
      PGC-1alpha mRNA levels, were decreased in the skeletal muscle of COPD patients
      compared with healthy controls. The cachectic COPD subgroup was further
      characterised by decreased PPAR-alpha mRNA expression and decreased TFAM protein
      and mRNA levels compared with noncachectic COPD patients. In addition, PPAR-alpha
      mRNA levels in skeletal muscle correlated negatively with inflammatory markers in
      plasma. Therefore, a disturbed expression of these regulatory factors may well
      underlie the disturbed skeletal muscle functioning in chronic obstructive
      pulmonary disease.

PMID- 17459895
TI  - Hyperleptinaemia, respiratory drive and hypercapnic response in obese patients.
AB  - Leptin is a powerful stimulant of ventilation in rodents. In humans, resistance
      to leptin has been consistently associated with obesity. Raised leptin levels
      have been reported in subjects with sleep apnoea or obesity-hypoventilation
      syndrome. The aim of the present study was to assess, by multivariate analysis,
      the possible association between respiratory centre impairment and levels of
      serum leptin. In total, 364 obese subjects (body mass index >or=30 kg.m(-2))
      underwent the following tests: sleep studies, respiratory function tests,
      baseline and hypercapnic response (mouth occlusion pressure (P(0.1)), minute
      ventilation), fasting leptin levels, body composition and anthropometric
      measures. Subjects with airways obstruction on spirometry were excluded. Out of
      the 346 subjects undergoing testing, 245 were included in the current analysis.
      Lung volumes, age, log leptin levels, end-tidal carbon dioxide tension,
      percentage body fat and minimal nocturnal saturation were predictors for baseline
      P(0.1). The hypercapnic response test was performed by 186 subjects; log leptin
      levels were predictors for hypercapnic response in males, but not in females.
      Hyperleptinaemia is associated with a reduction in respiratory drive and
      hypercapnic response, irrespective of the amount of body fat. These data suggest
      the extension of leptin resistance to the respiratory centre.

PMID- 17459896
TI  - Upper airway collapsibility, dilator muscle activation and resistance in sleep
      apnoea.
AB  - The calibre of the upper airway is thought to be dependant upon its passive
      anatomy/collapsibility and the activation of pharyngeal dilator muscles. During
      awake periods, the more collapsible upper airway in obstructive sleep apnoea
      (OSA) increases the dilator muscle activity through a negative-pressure reflex. A
      direct correlation between the critical closing pressure (P(crit)), as a measure
      of anatomy/collapsability and electromyogram (EMG) activity of genioglossus EMG
      (GG-EMG) and tensor palatini EMG (TP-EMG), was hypothesised. The relationship
      between these indices and pharyngeal resistance (R(phar)) was also examined. The
      study involved eight males with a mean age of 48 (interquartile range 46-52) yrs
      with OSA, and an apnoea/hypopnoea index of 75 (65-101).hr(-1) on two nights
      breathing normally and on nasal continuous positive airway pressure (nCPAP). The
      P(crit )was measured during nonrapid eye movement sleep on nCPAP using brief,
      incremental reductions in mask pressure. GG-EMG and TP-EMG were measured breath
      by-breath, awake, during sleep onset and on nCPAP. R(phar) was measured using
      airway pressures and flow. Wakeful GG-EMG, early sleep TP-EMG and the sleep
      decrement in TP-EMG were directly related to P(crit). Muscle activation was
      negatively correlated with R(phar) for TP-EMG awake and GG-EMG early in sleep. In
      conclusion these results confirm that dilator muscle activation is directly
      related to airway narrowing and reduces resistance across patients with
      obstructive sleep apnoea.

PMID- 17459897
TI  - Radiological and functional changes over 3 years in young children with cystic
      fibrosis.
AB  - The aim of the present study was to evaluate airway disease progression assessed
      by chest radiology, expiratory interrupter resistance (Rint,exp) and spirometry
      in young children with cystic fibrosis (CF) over a 3-yr period. Two chest
      radiographs combined with two R(int,exp) measurements were performed with a 3-yr
      interval in 21 preschool children (age (mean+/-sd) 3.2+/-0.9 yrs) and 30
      schoolchildren with CF (age 7.2+/-1.9 yrs). Chest radiographs were scored using
      five different CF scoring systems and Rint,exp measurements were expressed as
      height-adjusted Z-scores. Spirometry was assessed in schoolchildren and the
      results were expressed as a percentage of predicted values. Chest radiograph
      scores worsened significantly over the 3-yr period and a tendency towards more
      pronounced changes was observed, especially for the Wisconsin score, in preschool
      children. Most preschool and schoolchildren had Rint,exp Z-scores within the
      normal range at start and follow-up, and the annual change in Rint,exp Z-score
      was not significant. In schoolchildren, only the forced expiratory volume in one
      second as a percentage of forced vital capacity declined significantly during the
      study period. In summary, in young children with cystic fibrosis, chest
      radiograph scores worsen significantly over time even while lung function remains
      stable.

PMID- 17459898
TI  - Pulmonary Mycobacterium avium complex infection: association with NRAMP1
      polymorphisms.
AB  - The present study aimed to elucidate risk factors for nonimmunocompromised
      pulmonary Mycobacterium avium complex (MAC) infection. Epidemiological data and
      variations of candidate genes for mycobacterial diseases were analysed in 111
      patients with pulmonary MAC infection. Four polymorphisms of the human natural
      resistance-associated macrophage protein (NRAMP)1 gene, the 5'(GT)n, 469+14 G/C,
      D543N and the 3'untranslated region (3'TGTG) insertion/deletion, were genotyped
      using PCR-based methods. Fok I and Taq I polymorphisms of the vitamin D receptor
      gene and -221 X/Y and codon 54 A/B polymorphisms of the mannose binding lectin
      gene were also evaluated. Females were more susceptible to MAC infection mainly
      affecting the right middle lobe or lingular segment of the lung. Patients'
      residence at the onset of the disease was distributed evenly irrespective of a
      waterfront or city water supply system. As compared with homozygotes for major
      alleles of the D543N and TGTG insertion/deletion polymorphism of the NRAMP1 gene,
      heterozygotes containing minor alleles were less often observed in MAC cases than
      in controls. This genetic effect was more significant in patients without
      comorbidity but not in patients with comorbidity. Other polymorphisms did not
      show any association with the MAC infection. The human natural resistance
      associated macrophage protein 1 gene might be involved in susceptibility to
      pulmonary Mycobacterium avium complex infection.

PMID- 17459899
TI  - The role of atypical respiratory pathogens in exacerbations of chronic
      obstructive pulmonary disease.
AB  - The aetiology of acute exacerbations of chronic obstructive pulmonary disease
      (COPD) is heterogeneous and still under discussion. Serological studies have
      suggested that Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella
      pneumophila may play a role in acute exacerbations of COPD. The presence of these
      atypical pathogens in sputum samples was investigated in patients with stable
      COPD and with acute exacerbations of COPD using real-time PCR. The present study
      was part of a randomised, double-blind, single-centre study and a total of 248
      sputum samples from 104 COPD patients were included. In total, 122 samples
      obtained during stable disease (stable-state sputa) and 126 samples obtained
      during acute exacerbations of COPD (exacerbation sputa) were tested. Of the 122
      stable-state sputa, all samples were negative for M. pneumoniae and C. pneumoniae
      DNA, whereas one sample was positive for Legionella non-pneumophila DNA. Of the
      126 exacerbation sputa, all samples were negative for M. pneumoniae and C.
      pneumoniae DNA, whereas one sample was positive for Legionella non-pneumophila
      DNA. The possible relationship between the presence of atypical pathogens and the
      aetiology of acute exacerbations in chronic obstructive pulmonary disease was
      investigated in patients with stable disease and in those with acute
      exacerbations using real-time PCR. No indication was found of a role for
      Legionella spp., Chlamydia pneumoniae or Mycoplasma pneumoniae in stable,
      moderately severe chronic obstructive pulmonary disease and in its exacerbations.

PMID- 17459900
TI  - Risk of dementia in stroke-free patients diagnosed with atrial fibrillation: data
      from a community-based cohort.
AB  - AIMS: To estimate the incidence of dementia after the first atrial fibrillation
      (AF), and its impact on survival in a community-based cohort. METHODS AND
      RESULTS: Olmsted County, Minnesota adult residents diagnosed with first AF during
      1986-2000 were identified, and followed until 2004. The primary outcome was new
      detection of dementia. Interim stroke was censored in the analyses. Of 2837
      subjects (71 +/- 15 years old) diagnosed with first AF and without any evidence
      of cognitive dysfunction or stroke at the time of AF onset, 299 were diagnosed
      with dementia during a median follow-up of 4.6 years [interquartile (IQR) range
      1.5-7.9 years], and 1638 died. The Kaplan-Meier cumulative rate of dementia was
      2.7% at 1 year and 10.5% at 5 years. After adjustment for age and sex, dementia
      was strongly related to advancing age [hazard ratio (HR)/10 years, 2.8; 95%
      confidence interval (CI), 2.5-3.2], but did not vary with sex (P = 0.52). The
      occurrence of post-AF dementia was associated with significantly increased
      mortality risk (HR 2.9; 95% CI 2.5-3.3), even after adjustment for multiple
      comorbidities, and did not vary with age (P = 0.75) or sex (P = 0.33).
      CONCLUSION: Dementia appeared common following the diagnosis of first AF, and was
      associated with premature death.

PMID- 17459901
TI  - Effect of nitric oxide synthase inhibition on haemodynamics and outcome of
      patients with persistent cardiogenic shock complicating acute myocardial
      infarction: a phase II dose-ranging study.
AB  - AIMS: Previous studies suggested haemodynamic benefits and, possibly, mortality
      reduction with the use of nitric oxide synthase (NOS) inhibition in patients with
      acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). We
      assessed preliminary efficacy and safety of four doses of l-n-monomethyl-arginine
      (l-NMMA), a non-selective NOS inhibitor, in patients with AMI complicated by CS
      despite an open infarct-related artery. METHODS AND RESULTS: Patients (n = 79)
      were randomly assigned to a bolus and 5 h infusion of placebo or 0.15, 0.5, 1.0,
      or 1.5 mg/kg of l-NMMA. The primary outcome measure was absolute change in mean
      arterial pressure (MAP) at 2 h. Fifteen minutes after study drug initiation, mean
      change in MAP was -4.0 mmHg in the placebo group and 5.8 (P = 0.02), 4.8 (P =
      0.02), 5.1 (P = 0.07), and 11.6 (P < 0.001) mmHg in the four l-NMMA groups,
      respectively (all vs. placebo). Mean change in MAP at 2 h was -0.4, 4.4, 1.8, 
      4.1, and 6.8 mmHg in the placebo and four l-NMMA groups, respectively (all P =
      NS). CONCLUSION: l-NMMA resulted in modest increases in MAP at 15 min compared
      with placebo but there were no differences at 2 h.

PMID- 17459902
TI  - Prognosis of all-cause heart failure and borderline left ventricular systolic
      dysfunction: 5 year mortality follow-up of the Echocardiographic Heart of England
      Screening Study (ECHOES).
AB  - AIMS: Heart failure (HF) is reported to have an essentially malignant prognosis
      that can be modified by several interventions. Most outcome data on HF are
      available from randomized controlled treatment trials and longitudinal
      epidemiological studies. However, for a number of reasons, neither type of study
      have, to date, provided generalizable data on HF mortality. Furthermore, data on
      the prognosis of borderline left ventricular systolic dysfunction (LVSD) are even
      more limited. METHODS AND RESULTS: ECHOES (Echocardiographic Heart of England
      Screening Study) screened a total of 6,162 patients from a total of 10,161
      invited (61% response rate). Patients were randomly selected from four pre
      specified cohorts: the general population, diuretic users, those with a prior
      clinical label of HF, and a population with risk factors for HF, to identify the
      prevalence of HF and LVSD based on clinical assessment, ECG, and
      echocardiography. Causes of death during a 5-9 year follow-up period were
      recorded from routine mortality statistics. The 5-year survival rate of the
      general population was 93%, compared with 69% of those with LVSD without HF, 62%
      with HF and no LVSD, and 53% with HF plus LVSD. Survival improved significantly
      with increasing ejection fraction (EF) (log rank test for trend, chi(2) = 534.5,
      1, P < 0.0001). CONCLUSION: The ECHOES mortality data confirm the poor prognosis
      of patients suffering prevalent HF across the community with a mortality risk
      estimate of 9% per year. Borderline systolic dysfunction (EF 40-50%) on
      echocardiography carries a poor prognosis.

PMID- 17459903
TI  - Importance of left ventricular lead position in cardiac resynchronization
      therapy.

PMID- 17459904
TI  - Leaky ryanodine receptors cause delayed afterdepolarizations and ventricular
      arrhythmias.

PMID- 17459905
TI  - Submandibular approach for tracheal intubation in patients with panfacial
      fractures.
AB  - BACKGROUND: The oral route for tracheal intubation can interfere with some
      maxillofacial surgical procedures. At the same time, the nasal route can be
      contraindicated or impossible. Tracheostomy is the usual solution in these
      circumstances, but it carries a high incidence of complications. We tested the
      submandibular route for tracheal intubation as an alternative to tracheostomy in
      such situations. METHODS: The procedure was performed in 13 patients suffering
      from panfacial fractures associated with a fracture of skull base or a displaced
      nasal fracture, and in one patient with post-caustic burn scar affecting most of
      the face including the nose and requiring a full thickness skin flap surrounding
      the mouth. RESULTS: The technique was found easy and satisfactory for both the
      surgeon and the anaesthetist. It allowed uninterrupted surgical techniques and a
      secure airway. In six of the 13 patients, the submandibular tracheal tube was
      left in place for up to 44 h in the intensive care unit after the operation
      without complications or difficulties. Accidental dislodgement of the tube to the
      right main bronchus occurred in two patients while carrying out the procedure; it
      was rapidly detected and corrected. In another two patients, postoperative
      superficial infection occurred that responded well to local treatment. No other
      complications were encountered. CONCLUSIONS: Submandibular tracheal intubation is
      a simple and effective technique for upper airway management in some
      maxillofacial surgical patients when both oral and nasal tracheal intubations are
      not convenient.

PMID- 17459906
TI  - Community views on health sector reform and their participation in health
      priority setting: case of Lushoto and Muheza districts, Tanzania.
AB  - BACKGROUND: Community participation (CP) is a key concept under 'primary health
      care' programmes and 'Health Sector Reform' (HSR) in many countries. However,
      international literature with current empirical evidence on CP in health priority
      setting and HSR in Tanzania is scanty. OBJECTIVES: To explore and describe
      community views on HSR and their participation in setting health priorities.
      METHODS: A multistage sampling of wards and villages was done, involving group
      discussions with members of households, Village Development Committees (VDCs) and
      Ward Development Committees (WDCs). RESULTS: Respondents at village and ward
      levels in both districts related HSR with a cost sharing system at public health
      facilities. Views on the advantages or disadvantages of HSR were mixed, most of
      the residents pointing out that user charges burden the poor, there is a shortage
      of drugs at peripheral health facilities, the performance of government health
      service staff and village health workers does not satisfy community needs, health
      insurance is promoted more than people actually benefit, VDC and WDC poorly
      function as compared to local community-participatory priority-setting
      structures. CONCLUSION: HSR may not meet the desired health needs unless more
      efforts are made to enhance the performance of the existing HSR structures and
      community knowledge and enhance trust and participation in the health sector
      programmes at all levels.

PMID- 17459908
TI  - S100A1: a novel inotropic regulator of cardiac performance. Transition from
      molecular physiology to pathophysiological relevance.
AB  - Here we review the considerable body of evidence that has accumulated to support
      the notion of S100A1, a cardiac-specific Ca(2+)-sensor protein of the EF-hand
      type, as a physiological regulator of excitation-contraction coupling and
      inotropic reserve mechanisms in the mammalian heart. In particular, molecular
      mechanisms will be discussed conveying the Ca(2+)-dependent inotropic actions of
      S100A1 protein in cardiomyocytes occurring independently of beta-adrenergic
      signaling. Moreover, we will shed light on the molecular structure-function
      relationship of S100A1 with its cardiac target proteins at the sarcoplasmic
      reticulum, the sarcomere, and the mitochondria. Furthermore, pathophysiological
      consequences of disturbed S100A1 protein expression on altered Ca(2+) handling
      and intertwined systems in failing myocardium will be highlighted. Subsequently,
      therapeutic options by means of genetic manipulation of cardiac S100A1 expression
      will be discussed, aiming to complete our current understanding of the role of
      S100A1 in diseased myocardium.

PMID- 17459909
TI  - Skeletal muscle nNOS mu protein content is increased by exercise training in
      humans.
AB  - The major isoform of nitric oxide synthase (NOS) in skeletal muscle is the splice
      variant of neuronal NOS, termed nNOS mu. Exercise training increases nNOS mu
      protein levels in rat skeletal muscle, but data in humans are conflicting. We
      performed two studies to determine 1) whether resting nNOS mu protein expression
      is greater in skeletal muscle of 10 endurance-trained athletes compared with 11
      sedentary individuals (study 1) and 2) whether intense short-term (10 days)
      exercise training increases resting nNOS mu protein (within whole muscle and also
      within types I, IIa, and IIx fibers) in eight sedentary individuals (study 2). In
      study 1, nNOS mu protein was approximately 60% higher (P < 0.05) in endurance
      trained athletes compared with the sedentary participants. In study 2, nNOS mu
      protein expression was similar in types I, IIa, and IIx fibers before training.
      Ten days of intense exercise training significantly (P < 0.05) increased nNOS mu
      protein levels in types I, IIa, and IIx fibers, a finding that was validated by
      using whole muscle samples. Endothelial NOS and inducible NOS protein were barely
      detectable in the skeletal muscle samples. In conclusion, nNOS mu protein
      expression is greater in endurance-trained individuals when compared with
      sedentary individuals. Ten days of intense exercise is also sufficient to
      increase nNOS mu expression in untrained individuals, due to uniform increases of
      nNOS mu within types I, IIa, and IIx fibers.

PMID- 17459910
TI  - Intermittent hypoxia reduces upper airway stability in lean but not obese Zucker
      rats.
AB  - Obstructive sleep apnea involves intermittent periods of airway occlusions that
      lead to repetitive oxygen desaturations. Exposure to chronic intermittent hypoxia
      (IH) in rats increases diurnal blood pressure and alters skeletal muscle
      physiology. The impact of IH on upper airway muscle function is unknown. We
      hypothesize that IH exposure increases upper airway collapsibility in rats due to
      alterations of the muscles surrounding the upper airway. Lean and obese rats were
      exposed to cyclic alterations in O(2) levels (20.6%-5%) every 90 s, 8 h/day for 6
      days/wk for 12 wk. Following the exposure period, arterial pressure was recorded
      via the tail artery in conscious unrestrained rats. Mean arterial pressure was
      increased in lean IH but not in obese IH-exposed Zucker rats (P < 0.05). The
      pharyngeal pressure associated with airway collapse (P(crit)) was measured under
      anesthesia during baseline conditions and then during supramaximal stimulation of
      the hypoglossal nerve (cnXII). Baseline P(crit) was more positive (more
      collapsible) in lean but not obese rats following 12 wk of IH (P < 0.05), while
      supramaximal stimulation of cnXII increased airway stability (decreased P(crit))
      in both lean and obese Zucker rats following IH to levels that were similar to
      their respective room air controls. The in vitro peak tension and the expression
      of the individual myosin heavy chain isoforms from the upper airway muscles were
      unaltered following IH. We conclude that IH leads to increases in baseline
      collapsibility in lean Zucker rats exposed to IH by nonmyogenic mechanisms.

PMID- 17459911
TI  - The principle of homeostasis in the hypothalamus-pituitary-adrenal system: new
      insight from positive feedback.
AB  - Feedback control, both negative and positive, is a fundamental feature of
      biological systems. Some of these systems strive to achieve a state of
      equilibrium or "homeostasis". The major endocrine systems are regulated by
      negative feedback, a process believed to maintain hormonal levels within a
      relatively narrow range. Positive feedback is often thought to have a
      destabilizing effect. Here, we present a "principle of homeostasis," which makes
      use of both positive and negative feedback loops. To test the hypothesis that
      this homeostatic concept is valid for the regulation of cortisol, we assessed
      experimental data in humans with different conditions (gender, obesity, endocrine
      disorders, medication) and analyzed these data by a novel computational approach.
      We showed that all obtained data sets were in agreement with the presented
      concept of homeostasis in the hypothalamus-pituitary-adrenal axis. According to
      this concept, a homeostatic system can stabilize itself with the help of a
      positive feedback loop. The brain mineralocorticoid and glucocorticoid receptors
      with their known characteristics-fulfill the key functions in the homeostatic
      concept: binding cortisol with high and low affinities, acting in opposing
      manners, and mediating feedback effects on cortisol. This study supports the
      interaction between positive and negative feedback loops in the hypothalamus
      pituitary-adrenal system and in this way sheds new light on the function of dual
      receptor regulation. Current knowledge suggests that this principle of
      homeostasis could also apply to other biological systems.

PMID- 17459912
TI  - Central and baroreflex control of heart period during the wake-sleep cycle in
      spontaneously hypertensive rats.
AB  - We investigated whether the relative contribution of the baroreflex and central
      commands to the control of heart period differs between spontaneously
      hypertensive rats (SHR) and Wistar-Kyoto normotensive rats (WKY) during
      physiological behavior. Rats were instrumented with an arterial catheter and with
      electrodes for discriminating wakefulness, nonrapid eye movement sleep (NREMS),
      and rapid eye movement sleep (REMS). The cross-correlation function (CCF) between
      spontaneous fluctuations of heart period and mean arterial pressure was computed
      at frequencies <0.2 Hz. The baroreflex determines a positive correlation between
      heart period and previous pressure values. This pattern was observed in the CCF
      during quiet wakefulness (QW) and NREMS, and in QW, it was accompanied by a
      pronounced negative correlation between heart period and subsequent pressure
      values. The relative baroreflex contribution to the control of heart period,
      estimated from the positive peak value of the CCF, was lower in SHR than in WKY
      during QW but not during NREMS. During REMS, the CCF showed a negative
      correlation between heart period and both previous and subsequent pressure
      values, reflecting the prevalence of central autonomic commands. The relative
      contribution of central commands to the control of heart period, estimated from
      the negative peak value of the CCF, was lower in SHR than in WKY during REMS.
      These results suggest that during QW and REMS, the control of heart period
      exerted by the baroreflex and central commands, respectively, is less effective
      in SHR than in WKY. This difference is not apparent in a behavioral state of
      autonomic stability such as NREMS.

PMID- 17459913
TI  - Adrenalectomy alters regulation of blood pressure and endothelial nitric oxide
      synthase in sheep: modulation by estradiol.
AB  - Hypoadrenocorticism produces more severe hypotension during the peripartal period
      in pregnant ewes and women. We hypothesized that estradiol increases the severity
      of hypotension after withdrawal of corticosteroids and that this results from
      combined effects of adrenalectomy and estradiol to increase endothelial nitric
      oxide synthase (eNOS). In study I, blood pressure and eNOS mRNA and protein in
      aorta, uterine, renal, and mesenteric arteries were measured in intact ewes or
      adrenalectomized ewes 18-20 h after cessation of infusion of cortisol and
      aldosterone; half of each group ewes were treated with estradiol. In study II,
      adrenalectomized ewes were similarly studied 22-28 h after withdrawal of
      corticosteroids. Estradiol treatment in both studies significantly increased eNOS
      mRNA and protein in uterine artery, whereas corticosteroid withdrawal decreased
      expression of eNOS mRNA and protein in uterine artery. In both studies,
      adrenalectomy and steroid withdrawal decreased mean arterial pressure. In study
      II, four of six adrenalectomized ewes not treated with estradiol showed dramatic
      phasic variations in blood pressure and heart rate with a period of approximately
      20 s, developing within 22-28 h after corticosteroid withdrawal. Although there
      was no effect of estradiol on blood pressure in study I, in study II, ewes
      treated with estradiol did not develop this pattern. Estradiol also slowed both
      the decline in plasma sodium and the rise in plasma potassium after
      corticosteroid withdrawal. These results disprove the hypothesis that estradiol
      increases the severity of hypotension during hypoadrenocorticism. However, the
      study reveals an important effect of corticosteroid withdrawal on blood pressure,
      consistent with corticosteroid modulation of baroreflex responsiveness.

PMID- 17459914
TI  - Role of huddling on the energetic of growth in a newborn altricial mammal.
AB  - Huddling is considered as a social strategy to reduce thermal stress and promote
      growth in newborn altricial mammals. So far, the role of huddling on the
      allocation of saved energy has not been quantified nor have the related impacts
      on body temperature rhythms. To determine the energy partitioning of rabbit pups
      either raised alone or in groups of eight, four, or two individuals, when
      thermoregulatory inefficient (TI) and efficient (TE), we first investigated their
      total energy expenditure and body composition. We then monitored body temperature
      and activity rhythms to test whether huddling may impact these rhythms, centered
      on the suckling event. Pups in a group of eight utilized 40% less energy for
      thermogenesis when TI than did pups alone and 32% less energy when TE. Pups in
      groups of eight and four had significantly lower thermoregulatory costs in the TI
      period, whereas pups in groups of two, four, and eight had lower costs during the
      TE period. Huddling pups could therefore channel the energy saved into processes
      of growth and accrued more fat mass (on average 4.5 +/- 1.4 g) than isolated
      pups, which lost 0.7 g of fat. Pups in groups of four and eight had a body
      temperature significantly higher by 0.8 degrees C than pups in groups of two and
      one when TI, whereas no more differences were noted when the TE period was
      reached. Moreover, pups alone showed an endogenous circadian body temperature
      rhythm that differed when compared with that of huddling pups, with no rise
      before suckling. Thus huddling enables pups to invest the saved energy into
      growth and to regulate their body temperature to be more competitive during
      nursing, particularly at the early time when they are TI.

PMID- 17459915
TI  - Thigh muscle activation distribution and pulmonary VO2 kinetics during moderate,
      heavy, and very heavy intensity cycling exercise in humans.
AB  - The mechanisms underlying the oxygen uptake (Vo(2)) slow component during supra
      lactate threshold (supra-LT) exercise are poorly understood. Evidence suggests
      that the Vo(2) slow component may be caused by progressive muscle recruitment
      during exercise. We therefore examined whether leg muscle activation patterns
      [from the transverse relaxation time (T2) of magnetic resonance images] were
      associated with supra-LT Vo(2) kinetic parameters. Eleven subjects performed 6
      min cycle ergometry at moderate (80% LT), heavy (70% between LT and critical
      power; CP), and very heavy (7% above CP) intensities with breath-by-breath
      pulmonary Vo(2) measurement. T2 in 10 leg muscles was evaluated at rest and after
      3 and 6 min of exercise. During moderate exercise, nine muscles achieved a steady
      state T2 by 3 min; only in the vastus medialis did T2 increase further after 6
      min. During heavy exercise, T2 in the entire vastus group increased between
      minutes 3 and 6, and additional increases in T2 were seen in adductor magnus and
      gracilis during this period of very heavy exercise. The Vo(2) slow component
      increased with increasing exercise intensity (being functionally zero during
      moderate exercise). The distribution of T2 was more diverse as supra-LT exercise
      progressed: T2 variance (ms) increased from 3.6 +/- 0.2 to 6.5 +/- 1.7 between 3
      and 6 min of heavy exercise and from 5.5 +/- 0.8 to 12.3 +/- 5.4 in very heavy
      exercise (rest = 3.1 +/- 0.6). The T2 distribution was significantly correlated
      with the magnitude of the Vo(2) slow component (P < 0.05). These data are
      consistent with the notion that the Vo(2) slow component is an expression of
      progressive muscle recruitment during supra-LT exercise.

PMID- 17459916
TI  - Do we really need palliative care for severe dementia patients?

PMID- 17459917
TI  - Inhibition of the alpha/beta interferon response by mouse hepatitis virus at
      multiple levels.
AB  - Mouse hepatitis virus (MHV) was used as a model to study the interaction of
      coronaviruses with the alpha/beta interferon (IFN-alpha/beta) response. While MHV
      strain A59 appeared to induce IFN-beta gene transcription and low levels of
      nuclear translocation of the IFN-beta transcription factor interferon regulatory
      factor 3 (IRF-3), MHV did not induce IFN-beta protein production during the
      course of infection in L2 mouse fibroblast cells. In addition, MHV was able to
      significantly decrease the level of IFN-beta protein induced by both Newcastle
      disease virus (NDV) and Sendai virus infections, without targeting it for
      proteasomal degradation and without altering the nuclear translocation of IRF-3
      or IFN-beta mRNA production or stability. These results indicate that MHV
      infection causes an inhibition of IFN-beta production at a posttranscriptional
      level, without altering RNA or protein stability. In contrast, MHV induced IFN
      beta mRNA and protein production in the brains of infected animals, suggesting
      that the inhibitory mechanisms observed in vitro are not enough to prevent IFN
      alpha/beta production in vivo. Furthermore, MHV replication is highly resistant
      to IFN-alpha/beta action, as indicated by unimpaired MHV replication in L2 cells
      pretreated with IFN-beta. However, when L2 cells were coinfected with MHV and NDV
      in the presence of IFN-beta, NDV, but not MHV, replication was inhibited. Thus,
      rather than disarming the antiviral activity induced by IFN-beta pretreatment
      completely, MHV may be inherently resistant to some aspects of the antiviral
      state induced by IFN-beta. These findings show that MHV employs unique strategies
      to circumvent the IFN-alpha/beta response at multiple steps.

PMID- 17459918
TI  - Establishment of a cottontail rabbit papillomavirus/HLA-A2.1 transgenic rabbit
      model.
AB  - Three transgenic rabbit lines that express a well-characterized human major
      histocompatibility complex class I (MHC-I) gene (HLA-A2.1) have been established.
      All three lines carry the HLA-A2.1 heavy chain and are able to pass the transgene
      to their offspring with both the outbred and the inbred EIII/JC genetic
      background. HLA-A2.1 colocalizes exclusively with rabbit MHC-I on the cell
      surfaces. These HLA-A2.1 transgenic rabbits demonstrated infection patterns
      similar to those found after cottontail rabbit papillomavirus (CRPV) challenge
      when compared with results in normal rabbits, although higher regression rates
      were found in HLA-A2.1 transgenic rabbits. Because the CRPV genome can
      accommodate significant modifications, the CRPV/HLA-A2.1 rabbit model has the
      potential to be used to screen HLA-A2.1-restricted immunogenic epitopes from
      human papillomaviruses in the context of in vivo papillomavirus infection.

PMID- 17459919
TI  - Marek's disease virus type 2 (MDV-2)-encoded microRNAs show no sequence
      conservation with those encoded by MDV-1.
AB  - MicroRNAs (miRNAs) are increasingly being recognized as major regulators of gene
      expression in many organisms, including viruses. Among viruses, members of the
      family Herpesviridae account for the majority of the currently known virus
      encoded miRNAs. The highly oncogenic Marek's disease virus type 1 (MDV-1), an
      avian herpesvirus, has recently been shown to encode eight miRNAs clustered in
      the MEQ and LAT regions of the viral genome. The genus Mardivirus, to which MDV-1
      belongs, also includes the nononcogenic but antigenically related MDV-2. As MDV-1
      and MDV-2 are evolutionarily very close, we sought to determine if MDV-2 also
      encodes miRNAs. For this, we cloned, sequenced, and analyzed a library of small
      RNAs from the lymphoblastoid cell line MSB-1, previously shown to be coinfected
      with both MDV-1 and MDV-2. Among the 5,099 small RNA sequences determined from
      the library, we identified 17 novel MDV-2-specific miRNAs. Out of these, 16 were
      clustered in a 4.2-kb long repeat region that encodes R-LORF2 to R-LORF5. The
      single miRNA outside the cluster was located in the short repeat region, within
      the C-terminal region of the ICP4 homolog. The expression of these miRNAs in MSB
      1 cells and infected chicken embryo fibroblasts was further confirmed by Northern
      blotting analysis. The identification of miRNA clusters within the repeat regions
      of MDV-2 demonstrates conservation of the relative genomic positions of miRNA
      clusters in MDV-1 and MDV-2, despite the lack of sequence homology among the
      miRNAs of the two viruses. The identification of these novel miRNAs adds to the
      growing list of virus-encoded miRNAs.

PMID- 17459920
TI  - Human cytomegalovirus UL84 interacts with an RNA stem-loop sequence found within
      the RNA/DNA hybrid region of oriLyt.
AB  - Human cytomegalovirus (HCMV) lytic DNA replication is initiated at the complex
      cis-acting oriLyt region, which spans nearly 3 kb. DNA synthesis requires six
      core proteins together with UL84 and IE2. Previously, two essential regions were
      identified within oriLyt. Essential region I (nucleotides [nt] 92209 to 92573)
      can be replaced with the constitutively active simian virus 40 promoter, which in
      turn eliminates the requirement for IE2 in the origin-dependent transient
      replication assay. Essential region II (nt 92979 to 93513) contains two elements
      of interest: an RNA/DNA hybrid domain and an inverted repeat sequence capable of
      forming a stem-loop structure. Our studies now reveal for the first time that
      UL84 interacts with a stem-loop RNA oligonucleotide in vitro, and although UL84
      interacted with other nucleic acid substrates, a specific interaction occurred
      only with the RNA stem-loop. Increasing concentrations of purified UL84 produced
      a remarkable downward-staircase pattern, which is not due to a nuclease activity
      but is dependent upon the presence of secondary structures, suggesting that UL84
      modifies the conformation of the RNA substrate. Cross-linking experiments show
      that UL84 possibly changes the conformation of the RNA substrate. The addition of
      purified IE2 to the in vitro binding reaction did not affect binding to the stem
      loop structure. Chromatin immunoprecipitation assays performed using infected
      cells and purified virus show that UL84 is bound to oriLyt in a region adjacent
      to the RNA/DNA hybrid and the stem-loop structure. These results solidify UL84 as
      the potential initiator of HCMV DNA replication through a unique interaction with
      a conserved RNA stem-loop structure within oriLyt.

PMID- 17459921
TI  - Adenovirus E4 34k and E1b 55k oncoproteins target host DNA ligase IV for
      proteasomal degradation.
AB  - Cells infected by adenovirus E4 mutants accumulate end-to-end concatemers of the
      viral genome that are assembled from unit-length viral DNAs by nonhomologous end
      joining (NHEJ). Genome concatenation can be prevented by expression either of E4
      11k (product of E4orf3) or of the complex of E4 34k (product of E4orf6) and E1b
      55k. Both E4 11k and the E4 34k/E1b 55k complex prevent concatenation at least in
      part by inactivation of the host protein Mre11: E4 11k sequesters Mre11 in
      aggresomes, while the E4 34k/E1b 55k complex participates in a virus-specific E3
      ubiquitin ligase that mediates ubiquitination and proteasomal degradation. The E4
      34k/E1b 55k complex, but not E4 11k, also inhibits NHEJ activity on internal
      breaks in the viral genome and on V(D)J recombination substrate plasmids,
      suggesting that it may interfere with NHEJ independently of its effect on Mre11.
      We show here that DNA ligase IV, which performs the joining step of NHEJ, is
      degraded as a consequence of adenovirus infection. Degradation is dependent upon
      E4 34k and E1b 55k, functional proteasomes, and the activity of cellular cullin
      5, a component of the adenoviral ubiquitin ligase. DNA ligase IV also interacts
      physically with E1b 55k. The data demonstrate that DNA ligase IV, like Mre11, is
      a substrate for the adenovirus-specific E3 ubiquitin ligase; identify an
      additional viral approach to prevention of genome concatenation; and provide a
      mechanism for the general inhibition of NHEJ by adenoviruses.

PMID- 17459922
TI  - Atypical bZIP domain of viral transcription factor contributes to stability of
      dimer formation and transcriptional function.
AB  - The Epstein-Barr virus transcription factor Zta (encoded by BZLF1) is a bZIP
      protein containing an alpha-helical coiled-coil homodimerization motif (zipper).
      The Zta zipper forms less-stable dimers than other bZIP proteins, and an adjacent
      region (CT) interacts with the zipper to form a novel structure that is proposed
      to strengthen the dimer. Here we question the role of the CT region for Zta
      function. Cross-linking experiments demonstrate that the entire CT region lies
      adjacent to the zipper. Detailed analyses of Zta truncation mutations identify an
      involvement of the proximal CT region (221 to 230) in dimer formation with a
      further contribution from the distal region (236 to 243). Biophysical analyses
      reveal that residues 221 to 230 enhance the stability of the coiled coil. The
      ability of the Zta truncation mutants to interact with three Zta-binding sites
      also requires the proximal CT region. Fine mapping of DNA-binding requirements
      highlighted the contribution of these amino acids for Zta function. Thus, the
      proximal part of the CT region is required to aid the dimerization of Zta and
      thereby its DNA-binding ability. In contrast, although the distal part of the CT
      region aids dimerization, it promotes only a modest increase in DNA binding. To
      probe this further, we defined the contribution from the CT region for Zta to
      transactivate a promoter embedded within the viral genome. From this we conclude
      that the proximal part of the CT region is absolutely required, whereas the
      distal part is dispensable.

PMID- 17459923
TI  - Bystander attenuation of neuronal and astrocyte intercellular communication by
      murine cytomegalovirus infection of glia.
AB  - Astrocytes are the first cells infected by murine cytomegalovirus (MCMV) in
      primary cultures of brain. These cells play key roles in intercellular signaling
      and neuronal development, and they modulate synaptic activity within the nervous
      system. Using ratiometric fura-2 digital calcium imaging of >8,000 neurons and
      glia, we found that MCMV-infected astrocytes showed an increase in intracellular
      basal calcium levels and an enhanced response to neuroactive substances,
      including glutamate and ATP, and to high potassium levels. Cultured neurons with
      no sign of MCMV infection showed attenuated synaptic signaling after infection of
      the underlying astrocyte substrate, and intercellular communication between
      astrocytes with no sign of infection was reduced by the presence of infected
      glia. These bystander effects would tend to cause further deterioration of
      cellular communication in the brain in addition to the problems caused by the
      loss of directly infected cells.

PMID- 17459924
TI  - Diverse herpes simplex virus type 1 thymidine kinase mutants in individual human
      neurons and Ganglia.
AB  - Mutations in the thymidine kinase gene (tk) of herpes simplex virus type 1 (HSV
      1) explain most cases of virus resistance to acyclovir (ACV) treatment.
      Mucocutaneous lesions of patients with ACV resistance contain mixed populations
      of tk mutant and wild-type virus. However, it is unknown whether human ganglia
      also contain mixed populations since the replication of HSV tk mutants in animal
      neurons is impaired. Here we report the detection of mutated HSV tk sequences in
      human ganglia. Trigeminal and dorsal root ganglia were obtained at autopsy from
      an immunocompromised woman with chronic mucocutaneous infection with ACV
      resistant HSV-1. The HSV-1 tk open reading frames from ganglia were amplified by
      PCR, cloned, and sequenced. tk mutations were detected in a seven-G homopolymer
      region in 11 of 12 ganglia tested, with clonal frequencies ranging from 4.2 to
      76% HSV-1 tk mutants per ganglion. In 8 of 11 ganglia, the mutations were
      heterogeneous, varying from a deletion of one G to an insertion of one to three G
      residues, with the two-G insertion being the most common. Each ganglion had its
      own pattern of mutant populations. When individual neurons from one ganglion were
      analyzed by laser capture microdissection and PCR, 6 of 14 HSV-1-positive neurons
      were coinfected with HSV tk mutants and wild-type virus, 4 of 14 were infected
      with wild-type virus alone, and 4 of 14 were infected with tk mutant virus alone.
      These data suggest that diverse tk mutants arise independently under drug
      selection and establish latency in human sensory ganglia alone or together with
      wild-type virus.

PMID- 17459925
TI  - Essential role of dengue virus envelope protein N glycosylation at asparagine-67
      during viral propagation.
AB  - Dengue virus envelope protein (E) contains two N-linked glycosylation sites, at
      Asn-67 and Asn-153. The glycosylation site at position 153 is conserved in most
      flaviviruses, while the site at position 67 is thought to be unique for dengue
      viruses. N-linked oligosaccharide side chains on flavivirus E proteins have been
      associated with viral morphogenesis, infectivity, and tropism. Here, we examined
      the relevance of each N-linked glycan on dengue virus E protein by removing each
      site in the context of infectious viral particles. Dengue viruses lacking Asn-67
      were able to infect mammalian cells and translate and replicate the viral genome,
      but production of new infectious particles was abolished. In addition, dengue
      viruses lacking Asn-153 in the E showed reduced infectivity. In contrast,
      ablation of one or both glycosylation sites yielded viruses that replicate and
      propagate in mosquito cells. Furthermore, we found a differential requirement of
      N-linked glycans for E secretion in mammalian and mosquito cells. While secretion
      of E lacking Asn-67 was efficient in mosquito cells, secretion of the same
      protein expressed in mammalian cells was dramatically impaired. Finally, we found
      that viruses lacking the carbohydrate at position 67 showed reduced infection of
      immature dendritic cells, suggesting interaction between this glycan and the
      lectin DC-SIGN. Overall, our data defined different roles for the two glycans
      present at the E protein during dengue virus infection, highlighting the
      involvement of distinct host functions from mammalian and mosquito cells during
      dengue virus propagation.

PMID- 17459926
TI  - Predictable alphabeta T-cell receptor selection toward an HLA-B*3501-restricted
      human cytomegalovirus epitope.
AB  - Human cytomegalovirus (HCMV) elicits a very large burden on the immune system,
      with approximately one in ten T cells being reserved solely to manage this
      infection. However, information on the clonotypic composition of these vast T
      cell populations is limited. In this study, we sequenced 116 T-cell receptor
      (TcR) alpha/beta-chains specific for the highly immunogenic HLA-B*3501-resticted
      epitope IPSINVHHY from the pp65 antigen. Interestingly, T cells recovered from
      all donors bore an identical or near-identical TRBV28/TRBJ1-4/TRAV17/TRAJ33 TcR.
      The ability to predict the responding alphabeta TcR repertoire before viral
      infection should prove a powerful tool for basic and clinical immunology.

PMID- 17459927
TI  - Viral alteration of cellular translational machinery increases defective
      ribosomal products.
AB  - Here we show that cells expressing genes inserted into Semliki Forest virus (SFV)
      vectors generate a large fraction of defective ribosomal products (DRiPs) due to
      frequent initiation on downstream Met residues. In monopolizing the host cell
      translational machinery, SFV reduces levels of translation eukaryotic initiation
      factor 4E (eIF4E), diminishes phosphorylation of ribosome subunit S6, and
      phosphorylates translation initiation factor eIF2alpha. We show that the last
      event is required for SFV mistranslation of inserted genes. Downstream initiation
      is suppressed by fusing inserted genes with the open reading frame encoding the
      SFV capsid, demonstrating that one function of the capsid element is to enable
      ribosomes to initiate translation in the proper location. These results show that
      in modifying translation, viral vectors can unpredictably increase the generation
      of truncated polypeptides and thereby the DRiP fraction of inserted gene
      products, which can potentially affect their yield, therapeutic efficacy, and
      immunogenicity.

PMID- 17459928
TI  - Acute resolving woodchuck hepatitis virus (WHV) infection is associated with a
      strong cytotoxic T-lymphocyte response to a single WHV core peptide.
AB  - Woodchucks infected with woodchuck hepatitis virus (WHV) are an excellent model
      for studying acute, self-limited and chronic hepadnaviral infections. Defects in
      the immunological response leading to chronicity are still unknown. Specific T
      helper cell responses to WHV core and surface antigens (WHcAg and WHsAg,
      respectively) are associated with acute resolving infection; however, they are
      undetectable in chronic infection. Up to now, cytotoxic T-lymphocyte (CTL)
      responses could not be determined in the woodchuck. In the present study, we
      detected virus-specific CTL responses by a CD107a degranulation assay. The
      splenocytes of woodchucks in the postacute phase of WHV infection (18 months
      postinfection) were isolated and stimulated with overlapping peptides covering
      the whole WHcAg. After 6 days, the cells were restimulated and stained for CD3
      and CD107a. One peptide (c96-110) turned out to be accountable for T-cell
      expansion and CD107a staining. Later, we applied the optimized degranulation
      assay to study the kinetics of the T-cell response in acute WHV infection. We
      found a vigorous T-cell response against peptide c96-110 with peripheral blood
      cells beginning at the peak of viral load (week 5) and lasting up to 15 weeks
      postinfection. In contrast, there was no T-cell response against peptide c96-110
      detectable in chronically WHV-infected animals. Thus, with this newly established
      flow cytometric degranulation assay, we detected for the first time virus
      specific CTLs and determined one immunodominant epitope of WHcAg in the
      woodchuck.

PMID- 17459929
TI  - Identification of residues critical for the interferon antagonist function of
      Langat virus NS5 reveals a role for the RNA-dependent RNA polymerase domain.
AB  - All pathogenic flaviviruses examined thus far inhibit host interferon (IFN)
      responses by suppressing the Janus kinase-signal transducer and activator of
      transcription (JAK-STAT) pathway. Both Langat virus (LGTV; a member of the tick
      borne encephalitis virus serogroup) and Japanese encephalitis virus use the
      nonstructural protein NS5 to suppress JAK-STAT signaling. However, NS5 is also
      critical to virus replication, contributing methyltransferase and RNA-dependent
      RNA polymerase (RdRP) activities. The specific amino acid residues of NS5
      involved in IFN antagonism are not known. Here, we demonstrate that the LGTV NS5
      JAK-STAT inhibitory domain is contained between amino acids 355 and 735 (of 903),
      a range which lies within the RdRP domain. Furthermore, we identified two
      noncontiguous stretches of specific amino acids within the RdRP, 374 to 380 and
      624 to 647, as critical for inhibition of JAK-STAT signaling. Despite
      considerable separation on the linear NS5 sequence, these residues localized
      adjacent to each other when modeled on the West Nile virus RdRP crystal
      structure. Due to the general conservation of RdRP structures, these results
      suggest that the specific residues identified act cooperatively to form a unique
      functional site on the RdRP responsible for JAK-STAT inhibition. This insight
      into the mechanism underlying flavivirus IFN evasion strategies will facilitate
      the design of antiviral therapeutics that potentiate the action of IFN during
      infection.

PMID- 17459930
TI  - Inefficient transmission of H5N1 influenza viruses in a ferret contact model.
AB  - The abilities to infect and transmit efficiently among humans are essential for a
      novel influenza A virus to cause a pandemic. To evaluate the pandemic potential
      of widely disseminated H5N1 influenza viruses, a ferret contact model using
      experimental groups comprised of one inoculated ferret and two contact ferrets
      was used to study the transmissibility of four human H5N1 viruses isolated from
      2003 to 2006. The effects of viral pathogenicity and receptor binding specificity
      (affinity to synthetic sialosaccharides with alpha2,3 or alpha2,6 linkages) on
      transmissibility were assessed. A/Vietnam/1203/04 and A/Vietnam/JP36-2/05
      viruses, which possess "avian-like" alpha2,3-linked sialic acid (SA) receptor
      specificity, caused neurological symptoms and death in ferrets inoculated with
      10(3) 50% tissue culture infectious doses. A/Hong Kong/213/03 and A/Turkey/65
      596/06 viruses, which show binding affinity for "human-like" alpha2,6-linked SA
      receptors in addition to their affinity for alpha2,3-linked SA receptors, caused
      mild clinical symptoms and were not lethal to the ferrets. No transmission of
      A/Vietnam/1203/04 or A/Turkey/65-596/06 virus was detected. One contact ferret
      developed neutralizing antibodies to A/Hong Kong/213/03 but did not exhibit any
      clinical signs or detectable virus shedding. In two groups, one of two naive
      contact ferrets had detectable virus after 6 to 8 days when housed together with
      the A/Vietnam/JP36-2/05 virus-inoculated ferrets. Infected contact ferrets showed
      severe clinical signs, although little or no virus was detected in nasal washes.
      This limited virus shedding explained the absence of secondary transmission from
      the infected contact ferret to the other naive ferret that were housed together.
      Our results suggest that despite their receptor binding affinity, circulating
      H5N1 viruses retain molecular determinants that restrict their spread among
      mammalian species.

PMID- 17459931
TI  - Enhanced antiviral activity against foot-and-mouth disease virus by a combination
      of type I and II porcine interferons.
AB  - Previously, we showed that type I interferon (alpha/beta interferon [IFN
      alpha/beta]) can inhibit foot-and-mouth disease virus (FMDV) replication in cell
      culture, and swine inoculated with 10(9) PFU of human adenovirus type 5
      expressing porcine IFN-alpha (Ad5-pIFN-alpha) were protected when challenged 1
      day later. In this study, we found that type II pIFN (pIFN-gamma) also has
      antiviral activity against FMDV in cell culture and that, in combination with
      pIFN-alpha, it has a synergistic antiviral effect. We also observed that while
      each IFN alone induced a number of IFN-stimulated genes (ISGs), the combination
      resulted in a synergistic induction of some ISGs. To extend these studies to
      susceptible animals, we inoculated groups of swine with a control Ad5, 10(8) PFU
      of Ad5-pIFN-alpha, low- or high-dose Ad5-pIFN-gamma, or a combination of Ad5-pIFN
      alpha and low- or high-dose Ad5-pIFN-gamma and challenged all groups with FMDV 1
      day later. The control group and the groups inoculated with either Ad5-pIFN-alpha
      or a low dose of Ad5-pIFN-gamma developed clinical disease and viremia. However,
      the group that received the combination of both Ad5-IFNs with the low dose of Ad5
      pIFN-gamma was completely protected from challenge and had no viremia. Similarly
      the groups inoculated with the combination of Ad5s with the higher dose of Ad5
      pIFN-gamma or with only high-dose Ad5-pIFN-gamma were protected. The protected
      animals did not develop antibodies against viral nonstructural (NS) proteins,
      while all infected animals were NS protein seropositive. No antiviral activity or
      significant levels of IFNs were detected in the protected groups, but there was
      an induction of some ISGs. The results indicate that the combination of type I
      and II IFNs act synergistically to inhibit FMDV replication in vitro and in vivo.

PMID- 17459932
TI  - Binding-site identification and genotypic profiling of hepatitis C virus
      polymerase inhibitors.
AB  - The search for hepatitis C virus polymerase inhibitors has resulted in the
      identification of several nonnucleoside binding pockets. The shape and nature of
      these binding sites differ across and even within diverse hepatitis C virus
      genotypes. These differences confront antiviral drug discovery with the challenge
      of finding compounds that are capable of inhibition in variable binding pockets.
      To address this, we have established a hepatitis C virus mutant and genotypic
      recombinant polymerase panel as a means of guiding medicinal chemistry through
      the elucidation of the site of action of novel inhibitors and profiling against
      genotypes. Using a genotype 1b backbone, we demonstrate that the recombinant
      P495L, M423T, M414T, and S282T mutant enzymes can be used to identify the binding
      site of an acyl pyrrolidine analog. We assess the inhibitory activity of this
      analog and other nonnucleoside inhibitors with our panel of enzyme isolates
      generated from clinical sera representing genotypes 1a, 1b, 2a, 2b, 3a, 4a, 5a,
      and 6a.

PMID- 17459933
TI  - DNA immunization with plasmids encoding fusion and nucleocapsid proteins of
      bovine respiratory syncytial virus induces a strong cell-mediated immunity and
      protects calves against challenge.
AB  - Respiratory syncytial viruses (RSV) are one of the most important respiratory
      pathogens of humans and cattle, and there is currently no safe and effective
      vaccine prophylaxis. In this study, we designed two codon-optimized plasmids
      encoding the bovine RSV fusion (F) and nucleocapsid (N) proteins and assessed
      their immunogenicity in young calves. Two administrations of both plasmids
      elicited low antibody levels but primed a strong cell-mediated immunity
      characterized by lymphoproliferative response and gamma interferon production in
      vitro and in vivo. Interestingly, this strong cellular response drastically
      reduced viral replication, clinical signs, and pulmonary lesions after a highly
      virulent challenge. Moreover, calves that were further vaccinated with a killed
      virus vaccine developed high levels of neutralizing antibody and were fully
      protected following challenge. These results indicate that DNA vaccination could
      be a promising alternative to the classical vaccines against RSV in cattle and
      could therefore open perspectives for vaccinating young infants.

PMID- 17459934
TI  - In vitro analysis of transneuronal spread of an alphaherpesvirus infection in
      peripheral nervous system neurons.
AB  - The neurotropic alphaherpesviruses invade and spread in the nervous system in a
      directional manner between synaptically connected neurons. Until now, this
      property has been studied only in living animals and has not been accessible to
      in vitro analysis. In this study, we describe an in vitro system in which
      cultured peripheral nervous system neurons are separated from their neuron
      targets by an isolator chamber ring. Using pseudorabies virus (PRV), an
      alphaherpesvirus capable of transneuronal spread in neural circuits of many
      animals, we have recapitulated in vitro all known genetic requirements for
      retrograde and anterograde transneuronal spread as determined previously in vivo.
      We show that in vitro transneuronal spread requires intact axons and the presence
      of the viral proteins gE, gI, and Us9. We also show that transneuronal spread is
      dependent on the viral glycoprotein gB, which is required for membrane fusion,
      but not on gD, which is required for extracellular spread. We demonstrate
      ultrastructural differences between anterograde- and retrograde-traveling
      virions. Finally, we show live imaging of dynamic fluorescent virion components
      in axons and postsynaptic target neurons.

PMID- 17459935
TI  - Highly conserved configuration of catalytic amino acid residues among calicivirus
      encoded proteases.
AB  - A common feature of caliciviruses is the proteolytic processing of the viral
      polyprotein catalyzed by the viral 3C-like protease encoded in open reading frame
      1 (ORF1). Here we report the identification and structural characterization of
      the protease domains and amino acid residues in sapovirus (SaV) and feline
      calicivirus (FCV). The in vitro expression and processing of a panel of truncated
      ORF1 polyproteins and corresponding mutant forms showed that the functional
      protease domain is 146 amino acids (aa) in SaV and 154 aa in FCV. Site-directed
      mutagenesis of the protease domains identified four amino acid residues essential
      to protease activities: H(31), E(52), C(116), and H(131) in SaV and H(39), E(60),
      C(122), and H(137) in FCV. A computer-assisted structural analysis showed that
      despite high levels of diversity in the primary structures of the protease
      domains in the family Caliciviridae, the configurations of the H, E, C, and H
      residues are highly conserved, with these residues positioned closely along the
      inner surface of the potential binding cleft for the substrate. These results
      strongly suggest that the H, E, C, and H residues are involved in the formation
      of a conserved catalytic surface of the SaV and FCV 3C-like proteases.

PMID- 17459936
TI  - Epstein-Barr virus entry.

PMID- 17459937
TI  - Dominance of a nonpathogenic glycoprotein gene over a pathogenic glycoprotein
      gene in rabies virus.
AB  - The nonpathogenic phenotype of the live rabies virus (RV) vaccine SPBNGAN is
      determined by an Arg-->Glu exchange at position 333 in the glycoprotein,
      designated GAN. We recently showed that after several passages of SPBNGAN in
      mice, an Asn-->Lys mutation arose at position 194 of GAN, resulting in GAK, which
      was associated with a reversion to the pathogenic phenotype. Because an RV
      vaccine candidate containing two GAN genes (SPBNGAN-GAN) exhibits increased
      immunogenicity in vivo compared to the single-GAN construct, we tested whether
      the presence of two GAN genes might also enhance the probability of reversion to
      pathogenicity. Comparison of SPBNGAN-GAN with RVs constructed to contain either
      both GAN and GAK genes (SPBNGAN-GAK and SPBNGAK-GAN) or two GAK genes (SPBNGAK
      GAK) showed that while SPBNGAK-GAK was pathogenic, SPBNGAN-GAN and SPBNGAN-GAK
      were completely nonpathogenic and SPBNGAK-GAN showed strongly reduced
      pathogenicity. Analysis of genomic RV RNA in mouse brain tissue revealed
      significantly lower virus loads in SPBNGAN-GAK- and SPBNGAK-GAN-infected brains
      than those detected in SPBNGAK-GAK-infected brains, indicating the dominance of
      the nonpathogenic phenotype determined by GAN over the GAK-associated pathogenic
      phenotype. Virus production and viral RNA synthesis were markedly higher in
      SPBNGAN-, SPBNGAK-GAN-, and SPBNGAN-GAK-infected neuroblastoma cells than in the
      SPBNGAK- and SPBNGAK-GAK-infected counterparts, suggesting control of GAN
      dominance at the level of viral RNA synthesis. These data point to the lower risk
      of reversion to pathogenicity of a recombinant RV carrying two identical GAN
      genes compared to that of an RV carrying only a single GAN gene.

PMID- 17459938
TI  - Detection of a novel and highly divergent coronavirus from asian leopard cats and
      Chinese ferret badgers in Southern China.
AB  - Since an outbreak of severe acute respiratory syndrome (SARS) was averted in
      2004, many novel coronaviruses have been recognized from different species,
      including humans. Bats have provided the most diverse assemblages of
      coronaviruses, suggesting that they may be the natural reservoir. Continued
      virological surveillance has proven to be the best way to avert this infectious
      disease at the source. Here we provide the first description of a previously
      unidentified coronavirus lineage detected from wild Asian leopard cats
      (Prionailurus bengalensis) and Chinese ferret badgers (Melogale moschata) during
      virological surveillance in southern China. Partial genome analysis revealed a
      typical coronavirus genome but with a unique putative accessory gene
      organization. Phylogenetic analyses revealed that the envelope, membrane, and
      nucleoprotein structural proteins and the two conserved replicase domains,
      putative RNA-dependent RNA polymerase and RNA helicase, of these novel
      coronaviruses were most closely related to those of group 3 coronaviruses
      identified from birds, while the spike protein gene was most closely related to
      that of group 1 coronaviruses from mammals. However, these viruses always fell
      into an outgroup phylogenetic relationship with respect to other coronaviruses
      and had low amino acid similarity to all known coronavirus groups, indicating
      that they diverged early in the evolutionary history of coronaviruses. These
      results suggest that these viruses may represent a previously unrecognized
      evolutionary pathway, or possibly an unidentified coronavirus group. This study
      demonstrates the importance of systematic virological surveillance in market
      animals for understanding the evolution and emergence of viruses with infectious
      potential.

PMID- 17459940
TI  - Interaction of the C-terminal domains of sendai virus N and P proteins:
      comparison of polymerase-nucleocapsid interactions within the paramyxovirus
      family.
AB  - Interaction of the C-terminal domains of Sendai virus (SeV) P and N proteins is
      crucial for RNA synthesis by correctly positioning the polymerase complex (L+P)
      onto the nucleocapsid (N/RNA). To better understand this mechanism within the
      paramyxovirus family, we have studied the complex formed by the SeV C-terminal
      domains of P (PX) and N (N(TAIL)) proteins by solution nuclear magnetic resonance
      spectroscopy. We have characterized SeV N(TAIL), which belongs to the class of
      intrinsically disordered proteins, and precisely defined the binding regions
      within this latter domain and within PX. SeV N(TAIL) binds with residues 472 to
      493, which have a helical propensity (residues 477 to 491) to the surface created
      by helices alpha2 and alpha3 of PX with a 1:1 stoichiometry, as was also found
      for measles virus (MV). The binding interface is dominated by charged residues,
      and the dissociation constant was determined to be 57 +/- 18 microM under
      conditions of the experiment (i.e., in 0.5 M NaCl). We have also shown that the
      extreme C terminus of SeV N(TAIL) does not interact with PX, which is in contrast
      to MV, where a second binding site was identified. In addition, the interaction
      surfaces of the MV proteins are hydrophobic and a stronger binding constant was
      found. This gives a good illustration of how selection pressure allowed the C
      terminal domains of N and P proteins to evolve concomitantly within this family
      of viruses in order to lead to protein complexes having the same three
      dimensional fold, and thus the same function, but with completely different
      binding interfaces.

PMID- 17459939
TI  - Epstein-barr virus: environmental trigger of multiple sclerosis?

PMID- 17459941
TI  - Multiple restrictions of human immunodeficiency virus type 1 in feline cells.
AB  - The productive replication of human immunodeficiency virus type 1 (HIV-1) occurs
      exclusively in defined cells of human or chimpanzee origin, explaining why
      heterologous animal models for HIV replication, pathogenesis, vaccination, and
      therapy are not available. This lack of an animal model for HIV-1 studies
      prompted us to examine the susceptibility of feline cells in order to evaluate
      the cat (Felis catus) as an animal model for studying HIV-1. Here, we report that
      feline cell lines harbor multiple restrictions with respect to HIV-1 replication.
      The feline CD4 receptor does not permit virus infection. Feline T-cell lines MYA
      1 and FeT-1C showed postentry restrictions resulting in low HIV-1 luciferase
      reporter activity and low expression of viral Gag-Pol proteins when pseudotyped
      vectors were used. Feline fibroblastic CrFK and KE-R cells, expressing human CD4
      and CCR5, were very permissive for viral entry and HIV-long terminal repeat
      driven expression but failed to support spreading infection. KE-R cells displayed
      a profound block with respect to release of HIV-1 particles. In contrast, CrFK
      cells allowed very efficient particle production; however, the CrFK cell-derived
      HIV-1 particles had low specific infectivity. We subsequently identified feline
      apolipoprotein B-editing catalytic polypeptide 3 (feAPOBEC3) proteins as active
      inhibitors of HIV-1 particle infectivity. CrFK cells express at least three
      different APOBEC3s: APOBEC3C, APOBEC3H, and APOBEC3CH. While the feAPOBEC3C did
      not significantly inhibit HIV-1, the feAPOBEC3H and feAPOBEC3CH induced G to A
      hypermutations of the viral cDNA and reduced the infectivity approximately 10- to
      approximately 40-fold.

PMID- 17459942
TI  - A mathematical model of plasma membrane electrophysiology and calcium dynamics in
      vascular endothelial cells.
AB  - Vascular endothelial cells (ECs) modulate smooth muscle cell (SMC) contractility,
      assisting in vascular tone regulation. Cytosolic Ca(2+) concentration
      ([Ca(2+)](i)) and membrane potential (V(m)) play important roles in this process
      by controlling EC-dependent vasoactive signals and intercellular communication.
      The present mathematical model integrates plasmalemma electrophysiology and
      Ca(2+) dynamics to investigate EC responses to different stimuli and the
      controversial relationship between [Ca(2+)](i) and V(m). The model contains
      descriptions for the intracellular balance of major ionic species and the release
      of Ca(2+) from intracellular stores. It also expands previous formulations by
      including more detailed transmembrane current descriptions. The model reproduces
      V(m) responses to volume-regulated anion channel (VRAC) blockers and
      extracellular K(+) concentration ([K(+)](o)) challenges, predicting 1) that V(m)
      changes upon VRAC blockade are [K(+)](o) dependent and 2) a biphasic response of
      V(m) to increasing [K(+)](o). Simulations of agonist-induced Ca(2+) mobilization
      replicate experiments under control and V(m) hyperpolarization blockade
      conditions. They show that peak [Ca(2+)](i) is governed by store Ca(2+) release
      while Ca(2+) influx (and consequently V(m)) impacts more the resting and plateau
      [Ca(2+)](i). The V(m) sensitivity of rest and plateau [Ca(2+)](i) is dictated by
      a [Ca(2+)](i) "buffering" system capable of masking the V(m)-dependent
      transmembrane Ca(2+) influx. The model predicts plasma membrane Ca(2+)-ATPase and
      Ca(2+) permeability as main players in this process. The heterogeneous V(m)
      impact on [Ca(2+)](i) may elucidate conflicting reports on how V(m) influences EC
      Ca(2+). The present study forms the basis for the development of multicellular EC
      SMC models that can assist in understanding vascular autoregulation in health and
      disease.

PMID- 17459943
TI  - Ferritin: a novel mechanism for delivery of iron to the brain and other organs.
AB  - Traditionally, transferrin has been considered the primary mechanism for cellular
      iron delivery, despite suggestive evidence for additional iron delivery
      mechanisms. In this study we examined ferritin, considered an iron storage
      protein, as a possible delivery protein. Ferritin consists of H- and L-subunits,
      and we demonstrated iron uptake by ferritin into multiple organs and that the
      uptake of iron is greater when the iron is delivered via H-ferritin compared with
      L-ferritin. The delivery of iron via H-ferritin but not L-ferritin was
      significantly decreased in mice with compromised iron storage compared with
      control, indicating that a feedback mechanism exists for H-ferritin iron
      delivery. To further evaluate the mechanism of ferritin iron delivery into the
      brain, we used a cell culture model of the blood-brain barrier to demonstrate
      that ferritin is transported across endothelial cells. There are receptors that
      prefer H-ferritin on the endothelial cells in culture and on rat brain
      microvasculature. These studies identify H-ferritin as an iron transport protein
      and suggest the presence of an H-ferritin receptor for mediating iron delivery.
      The relative amount of iron that could be delivered via H-ferritin could make
      this protein a predominant player in cellular iron delivery.

PMID- 17459944
TI  - Insulin increases the expression of contractile phenotypic markers in airway
      smooth muscle.
AB  - We have previously demonstrated that long-term exposure of bovine tracheal smooth
      muscle (BTSM) strips to insulin induces a functional hypercontractile phenotype.
      To elucidate molecular mechanisms by which insulin might induce maturation of
      contractile phenotype airway smooth muscle (ASM) cells, we investigated effects
      of insulin stimulation in serum-free primary BTSM cell cultures on protein
      accumulation of specific contractile phenotypic markers and on the abundance and
      stability of mRNA encoding these markers. In addition, we used microscopy to
      assess insulin effects on ASM cell morphology, phenotype, and induction of
      phosphatidylinositol (PI) 3-kinase signaling. It was demonstrated that protein
      and mRNA levels of smooth muscle-specific contractile phenotypic markers,
      including sm-myosin, are significantly increased after stimulation of cultured
      BTSM cells with insulin (1 microM) for 8 days compared with cells treated with
      serum-free media, whereas mRNA stability was unaffected. In addition, insulin
      treatment promoted the formation of large, elongate ASM cells, characterized by
      dramatic accumulation of contractile phenotype marker proteins and phosphorylated
      p70(S6K) (downstream target of PI 3-kinase associated with ASM maturation).
      Insulin effects on protein accumulation and cell morphology were abrogated by
      combined pretreatment with the Rho kinase inhibitor Y-27632 (1 microM) or the PI
      3-kinase inhibitor LY-294002 (10 microM), indicating that insulin increases the
      expression of contractile phenotypic markers in BTSM in a Rho kinase- and PI 3
      kinase-dependent fashion. In conclusion, insulin increases transcription and
      protein expression of contractile phenotypic markers in ASM. This could have
      important implications for the use of recently approved aerosolized insulin
      formulations in diabetes mellitus.

PMID- 17459945
TI  - Relationship between Kir2.1/Kir2.3 activity and their distributions between
      cholesterol-rich and cholesterol-poor membrane domains.
AB  - Our earlier studies have shown that Kir2.x channels are suppressed by an increase
      in the level of cellular cholesterol, whereas cholesterol depletion enhances the
      activity of the channels. In this study, we show that Kir2.1 and Kir2.3 channels
      have double-peak distributions between cholesterol-rich (raft) and cholesterol
      poor (non-raft) membrane fractions, indicating that the channels exist in two
      different types of lipid environment. We also show that whereas methyl-beta
      cyclodextrin-induced cholesterol depletion removes cholesterol from both raft and
      non-raft membrane fractions, cholesterol enrichment results in cholesterol
      increase exclusively in the raft fractions. Kinetics of both depletion-induced
      Kir2.1 enhancement and enrichment-induced Kir2.1 suppression correlate with the
      changes in the level of raft cholesterol. Furthermore, we show not only that
      cholesterol depletion shifts the distribution of the channels from cholesterol
      rich to cholesterol-poor membrane fractions but also that cholesterol enrichment
      has the opposite effect. These observations suggest that change in the level of
      raft cholesterol alone is sufficient to suppress Kir2 activity and to facilitate
      partitioning of the channels to cholesterol-rich domains. Therefore, we suggest
      that partitioning to membrane rafts plays an important role in the sensitivity of
      Kir2 channels to cholesterol.

PMID- 17459946
TI  - Transport and regulatory characteristics of the yeast bicarbonate transporter
      homolog Bor1p.
AB  - The functional properties of the Saccharomyces cerevisiae bicarbonate transporter
      homolog Bor1p (YNL275wp) were characterized by measuring boron (H(3)BO(3)),
      Na(+), and Cl(-) fluxes. Neither Na(+) nor Cl(-) appears to be a transported
      substrate for Bor1p. Uphill efflux of boron mediated by Bor1p was demonstrated
      directly by loading cells with boron and resuspending in a low-boron medium.
      Cells with intact BOR1, but not the deletant strain, transport boron outward
      until the intracellular concentration is sevenfold lower than that in the medium.
      Boron efflux through Bor1p is a saturable function of intracellular boron
      (apparent K(m) approximately 1-2 mM). The extracellular pH dependences of boron
      distribution and efflux indicate that uphill efflux is driven by the inward H(+)
      gradient. Addition of 30 mM HCO(3)(-) does not affect boron extrusion by Bor1p,
      indicating that HCO(3)(-) does not participate in Bor1p function. Functional
      Bor1p is present in cells grown in medium with no added boron, and overnight
      growth in 10 mM H(3)BO(3) causes only a small increase in the levels of
      functional Bor1p and in BOR1 mRNA. The fact that Bor1p is expressed when there is
      no need for boron extrusion and is not strongly induced in the presence of growth
      inhibitory boron concentrations is surprising if the main physiological function
      of yeast Bor1p is boron efflux. A possible role in vacuolar dynamics for Bor1p
      was recently reported by Decker and Wickner. Under the conditions used presently,
      there appears to be mildly abnormal vacuolar morphology in the deletant strain.

PMID- 17459947
TI  - MicroRNA-206 is overexpressed in the diaphragm but not the hindlimb muscle of mdx
      mouse.
AB  - MicroRNAs are highly conserved, noncoding RNAs involved in posttranscriptional
      gene silencing. MicroRNAs have been shown to be involved in a range of biological
      processes, including myogenesis and muscle regeneration. The objective of this
      study was to test the hypothesis that microRNA expression is altered in
      dystrophic muscle, with the greatest change occurring, of the muscles examined,
      in the diaphragm. The expression of the muscle-enriched microRNAs was determined
      in the soleus, plantaris, and diaphragm muscles of control and dystrophin
      deficient (mdx) mice by semiquantitative PCR. In the soleus and plantaris,
      expression of the mature microRNA 133a (miR-133a) and miR-206, respectively, was
      decreased by approximately 25%, whereas in the diaphragm, miR-206 expression
      increased by 4.5-fold relative to control. The increased expression of miR-206 in
      the mdx diaphragm was paralleled by a 4.4-fold increase in primary miRNA-206 (pri
      miRNA-206) transcript level. Expression of Myod1 was elevated 2.7-fold only in
      the mdx diaphragm, consistent with an earlier finding demonstrating Myod1 can
      activate pri-miRNA-206 transcription. Transcript levels of Drosha and Dicer,
      major components of microRNA biogenesis pathway, were unchanged in mdx muscle,
      suggesting the pathway is not altered under dystrophic conditions. Previous in
      vitro analysis found miR-206 was capable of repressing utrophin expression;
      however, under dystrophic conditions, both utrophin transcript and protein levels
      were significantly increased by 69% and 3.9-fold, respectively, a finding
      inconsistent with microRNA regulation. These results are the first to report
      alterations in expression of muscle-enriched microRNAs in skeletal muscle of the
      mdx mouse, suggesting microRNAs may have a role in the pathophysiology of
      muscular dystrophy.

PMID- 17459948
TI  - Carbonic anhydrase XIV in skeletal muscle: subcellular localization and function
      from wild-type and knockout mice.
AB  - The expression of carbonic anhydrase (CA) XIV was investigated in mouse skeletal
      muscles. Sarcoplasmic reticulum (SR) and sarcolemmal (SL) membrane fractions were
      isolated from wild-type (WT) and CA XIV knockout (KO) mice. The CA XIV protein of
      54 kDa was present in SR and SL membrane fractions as shown by Western blot
      analysis. CA activity measurements of WT and KO membrane fractions showed that CA
      XIV accounts for approximately 50% and 66% of the total CA activities determined
      in the SR and SL fractions, respectively. This indicates the presence of at least
      one other membrane-associated CA isoform in these membranes, e.g., CA IV, CA IX,
      or CA XII. Muscle fibers of the extensor digitorum longus (EDL) muscle were
      immunostained with anti-CA XIV/FITC and anti-sarco(endo)plasmic reticulum Ca(2+)
      ATPase 1/TRITC, with anti-CA XIV/FITC and anti-ryanodine receptor/TRITC, or with
      anti-CA XIV/FITC and anti-monocarboxylate transporter-4/TRITC. CA XIV was
      expressed in the plasma membrane and in the longitudinal SR but not in the
      terminal SR. Isometric contraction measurements of single twitches and tetani and
      a fatigue protocol applied to fiber bundles of the fast-twitch EDL and of the
      slow-twitch soleus muscle from WT and KO mice showed that the lack of SR membrane
      associated CA XIV did not affect maximum force, rise and relaxation times, and
      fatigue behavior. Thus, it is concluded that a reduction of the total SR CA
      activity by approximately 50% in CA XIV KO mice does not lead to an impairment of
      SR function.

PMID- 17459949
TI  - O2(*-) production at 37 degrees C plays a critical role in depressing tetanic
      force of isolated rat and mouse skeletal muscle.
AB  - To find out whether the decrease in muscle performance of isolated mammalian
      skeletal muscle associated with the increase in temperature toward physiological
      levels is related to the increase in muscle superoxide (O(2)(*-)) production,
      O(2)(*-) released extracellularly by intact isolated rat and mouse extensor
      digitorum longus (EDL) muscles was measured at 22, 32, and 37 degrees C in Krebs
      Ringer solution, and tetanic force was measured in both preparations at 22 and 37
      degrees C under the same conditions. The rate of O(2)(*-) production increased
      marginally when the temperature was increased from 22 to 32 degrees C, but
      increased fivefold when the temperature was increased from 22 to 37 degrees C in
      both rat and mouse preparations. This increase was accompanied by a marked
      decrease in tetanic force after 30 min incubation at 37 degrees C in both rat and
      mouse EDL muscles. Tetanic force remained largely depressed after return to 22
      degrees C for up to 120 min. The specific maximum Ca(2+)-activated force measured
      in mechanically skinned fibers after the temperature treatment was markedly
      depressed in mouse fibers but was not significantly depressed in rat muscle
      fibers. The resting membrane and intracellular action potentials were, however,
      significantly affected by the temperature treatment in the rat fibers. The
      effects of the temperature treatment on tetanic force, maximum Ca(2+)-activated
      force, and membrane potential were largely prevented by 1 mM Tempol (4-hydroxy
      2,2,6,6-tetramethylpiperidine-1-oxyl), a membrane-permeable superoxide dismutase
      mimetic, indicating that the increased O(2)(*-) production at physiological
      temperatures is largely responsible for the observed depression in tetanic force
      at 37 degrees C by affecting the contractile apparatus and plasma membrane.

PMID- 17459950
TI  - Small- and intermediate-conductance Ca2+-activated K+ channels directly control
      agonist-evoked nitric oxide synthesis in human vascular endothelial cells.
AB  - The contribution of small-conductance (SK(Ca)) and intermediate-conductance
      Ca(2+)-activated K(+) (IK(Ca)) channels to the generation of nitric oxide (NO) by
      Ca(2+)-mobilizing stimuli was investigated in human umbilical vein endothelial
      cells (HUVECs) by combining single-cell microfluorimetry with perforated patch
      clamp recordings to monitor agonist-evoked NO synthesis, cytosolic Ca(2+)
      transients, and membrane hyperpolarization in real time. ATP or histamine evoked
      reproducible elevations in NO synthesis and cytosolic Ca(2+), as judged by 4
      amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM) and fluo-3 fluorescence,
      respectively, that were tightly associated with membrane hyperpolarizations.
      Whereas evoked NO synthesis was unaffected by either tetraethylammonium (10
      mmol/l) or BaCl(2) (50 micromol/l) + ouabain (100 micromol/l), depleting
      intracellular Ca(2+) stores by thapsigargin or removing external Ca(2+) inhibited
      NO production, as did exposure to high (80 mmol/l) external KCl. Importantly,
      apamin and charybdotoxin (ChTx)/ triarylmethane (TRAM)-34, selective blockers
      SK(Ca) and IK(Ca) channels, respectively, abolished both stimulated NO synthesis
      and membrane hyperpolarization and decreased evoked Ca(2+) transients. Apamin and
      TRAM-34 also inhibited an agonist-induced outwardly rectifying current
      characteristic of SK(Ca) and IK(Ca) channels. Under voltage-clamp control, we
      further observed that the magnitude of agonist-induced NO production varied
      directly with the degree of membrane hyperpolarization. Mechanistically, our data
      indicate that SK(Ca) and IK(Ca) channel-mediated hyperpolarization represents a
      critical early event in agonist-evoked NO production by regulating the influx of
      Ca(2+) responsible for endothelial NO synthase activation. Moreover, it appears
      that the primary role of agonist-induced release of intracellular Ca(2+) stores
      is to trigger the opening of both K(Ca) channels along with Ca(2+) entry channels
      at the plasma membrane. Finally, the observed inhibition of stimulated NO
      synthesis by apamin and ChTx/TRAM-34 demonstrates that SK(Ca) and IK(Ca) channels
      are essential for NO-mediated vasorelaxation.

PMID- 17459951
TI  - Oxidative stress reduces renal dopamine D1 receptor-Gq/11alpha G protein
      phospholipase C signaling involving G protein-coupled receptor kinase 2.
AB  - The dopamine D1 receptors (D1R), expressed in renal proximal tubules, participate
      in the regulation of sodium transport. A defect in the coupling of the D1R to its
      G protein/effector complex in renal tubules has been reported in various
      conditions associated with oxidative stress. Because G protein-coupled receptor
      kinases (GRKs) are known to play an important role in D1R desensitization, we
      tested the hypothesis that increased oxidative stress in obese Zucker rats may
      cause GRK2 upregulation and, subsequently, D1R dysfunction. Lean and obese rats
      were given normal diet or diet supplemented with antioxidant lipoic acid for 2
      wk. Compared with lean rats, obese rats exhibited oxidative stress, D1R were
      uncoupled from G(q/11)alpha at basal level, and SKF-38393 failed to elicit D1R-G
      protein coupling, stimulate phospholipase C (PLC), and inhibit Na-K-ATPase
      activity. These animals showed increased basal protein kinase C (PKC) activity
      and membranous translocation of GRK2 and increased GKR2-G(q/11)alpha interaction
      and D1R serine phosphorylation. Enzymatic dephosphorylation of D1R restored SKF
      38393-induced adenylyl cyclase stimulation but not PLC activation. Treatment of
      obese rats with lipoic acid restored D1R-G protein coupling and SKF-38393-induced
      PLC stimulation and Na-K-ATPase inhibition. Lipoic acid treatment also normalized
      PKC activity, GRK2 sequestration, and GKR2-G(q/11)alpha interaction. In
      conclusion, these data show that oxidative stress increases PKC activity causing
      GRK2 membranous translocation. GRK2 interacts with G(q/11)alpha and acts, at
      least in part, as a regulator of G protein signaling leading to the D1R
      G(q/11)alpha uncoupling, causing inability of SKF-38393 to stimulate PLC and
      inhibit Na/K-ATPase. Lipoic acid, while reducing oxidative stress, normalized PKC
      activity and restored D1R-G(q/11)alpha-PLC signaling and the ability of SKF-38393
      to inhibit Na-K-ATPase activity.

PMID- 17459952
TI  - Oxidative stress as a common pathway to chronic tubulointerstitial injury in
      kidney allografts.
AB  - A major challenge for kidney transplantation is to dissect out the identifiable
      causes of chronic allograft tubulointerstitial fibrosis and to develop cause
      specific treatment strategies. There has been a recent interest in the role of
      oxidative stress (OS) as a mediator of injury in chronic allograft tubular
      atrophy (TA) and interstitial fibrosis (IF). A review of the literature and data
      from my laboratory studying chronic allograft TA/IF in rat, rhesus monkey, and
      human kidneys suggests that OS is increased in graft-infiltrating macrophages,
      activated myofibroblasts, interstitium, and areas of tubular injury. Chronic
      allograft OS may be induced by inflammation, abnormal tissue oxygenation,
      immunosuppressant drugs, and comorbid clinical conditions including diabetes,
      hypertension, proteinuria, anemia, and dyslipidemia. Moreover, OS-induced chronic
      TA/IF is associated with signaling pathways including inflammation, apoptosis,
      hypoxia, and epithelial-to-mesenchymal transition. Most of these injury pathways
      participate in a self-perpetuating cycle with OS. In conclusion, evidence
      suggests that OS is a common mechanism of injury in chronic allograft TA/IF.
      However, most available data demonstrate a correlation and no causal
      relationship. Furthermore, the extent to which TA/IF is dependent on OS is
      unknown. These questions may be answered by prospective randomized placebo
      control trials examining the role of select antioxidants in the prevention of
      chronic allograft TA/IF.

PMID- 17459953
TI  - Identification and localization of BK-beta subunits in the distal nephron of the
      mouse kidney.
AB  - Large-conductance, Ca(2+)-activated K(+) channels (BK), comprised of pore-forming
      alpha- and accessory beta-subunits, secrete K(+) in the distal nephron under high
      flow and high-K(+) diet conditions. BK channels are detected by electrophysiology
      in many nephron segments; however, the accessory beta-subunit associated with
      these channels has not been determined. We performed RT-PCR, Western blotting,
      and immunohistochemical staining to determine whether BK-beta1 is localized to
      the connecting tubule's principal-like cells (CNT) or intercalated cells (ICs),
      and whether BK-beta2-4 are present in other distal nephron segments. RT-PCR and
      Western blots revealed that the mouse kidney expresses BK-beta1, BK-beta2, and BK
      beta4. Available antibodies in conjunction with BK-beta1(-/-) and BK-beta4(-/-)
      mice allowed the specific localization of BK-beta1 and BK-beta4 in distal nephron
      segments. Immunohistochemical staining showed that BK-beta1 is localized in the
      CNT but not ICs of the connecting tubule. The localization of BK-beta4 was
      discerned using an anti-BK-beta4 antibody on wild-type tissue and anti-GFP on GFP
      replaced BK-beta4 mouse (BK-beta4(-/-)) tissue. Both antibodies (anti-BK-beta4
      and anti-GFP) localized BK-beta4 to the thick ascending limb (TAL), distal
      convoluted tubule (DCT), and ICs of the distal nephron. It is concluded that BK
      beta1 is narrowly confined to the apical membrane of CNTs in the mouse, whereas
      BK-beta4 is expressed in the TAL, DCT, and ICs.

PMID- 17459954
TI  - Lack of a role of membrane-protein interactions in flow-dependent activation of
      ENaC.
AB  - Rates of Na(+) absorption in the distal nephron increase proportionally with the
      rates of tubular flow. We tested the hypothesis that the deformation or tension
      generated in the plasma membrane in response to flow activates the epithelial
      sodium channel (ENaC). We modified the physical properties of the membrane by
      changing the temperature and the content of cholesterol. Rates of net Na(+)
      absorption measured in cortical collecting ducts (CCDs) perfused at room
      temperature at slow (approximately 1) and fast (approximately 5 nl.min(-1).mm(
      1)) flow rates were less than those measured at 37 degrees C at the same flow
      rates, although increases in tubular fluid flow rates led to comparable relative
      increases in net Na(+) absorption at both temperatures. Xenopus laevis oocytes
      expressing ENaC responded to an increase in shear stress at 22-25 degrees C with
      a discrete delay followed by a monoexponential increase in whole-cell Na(+)
      currents. We observed that temperature affected 1) basal currents, 2) delay
      times, 3) kinetics of activation, and 4) fold-increase in macroscopic currents in
      response to flow. The magnitude of the response to flow displayed biphasic
      behavior as a function of temperature, with a minimal value at 25 degrees C.
      Steady-state fluorescence anisotropic measurements of purified plasma membranes
      did not show any obvious phase transition behavior over a temperature range from
      8.3 degrees C to 36.5 degrees C. Modification of the content of membrane
      cholesterol did not affect the response to flow. Our results suggest that the
      flow-dependent activation of ENaC is not influenced by modifications in the
      intrinsic properties of the plasma membrane.

PMID- 17459955
TI  - Renal physiology: an evolving field.

PMID- 17459956
TI  - Involvement of the CDK2-E2F1 pathway in cisplatin cytotoxicity in vitro and in
      vivo.
AB  - E2F1 is a key regulator that links cell cycle progression and cell death. E2F1
      activity is controlled by Cdk2-cyclin complexes via several mechanisms, such as
      phosphorylation of retinoblastoma protein (pRb) to release E2F1, direct
      phosphorylation, and stable physical interaction. We have demonstrated that
      cisplatin cytotoxicity depends on Cdk2 activity, and Cdk2 inhibition protects
      kidney cells from cisplatin-induced cell death in vitro and in vivo. Now we show
      that E2F1 is an important downstream effector of Cdk2 that accumulates in mouse
      kidneys and in cultured mouse proximal tubular cells (TKPTS) after cisplatin
      exposure by a Cdk2-dependent mechanism. Direct inhibition of E2F1 by transduction
      with adenoviruses expressing an E2F1-binding protein (TopBP1) protected TKPTS
      cells from cisplatin-induced apoptosis, whereas overexpression of E2F1 caused
      cell death. Moreover, E2F1 knockout mice were markedly protected against
      cisplatin nephrotoxicity by both functional and histological criteria.
      Collectively, cisplatin-induced cell death is dependent on Cdk2 activity, which
      is at least partly through the Cdk2-E2F1 pathway both in vitro and in vivo.

PMID- 17459957
TI  - Successful patient recruitment in investigator-led clinical trials.

PMID- 17459958
TI  - Combining enzyme specificity and tissue selectivity of cyclooxygenase inhibitors:
      towards better tolerability?
AB  - Inhibitors of cyclooxygenases (COXs) are the most widely used drugs. They reduce
      discomfort and fever, inhibit peri-operative and inflammatory pain. These effects
      are largely mediated by inhibition of cyclooxygenase-1 and -2 (COX-1 and COX-2)
      enzymes found throughout the body producing prostaglandins, which are important
      mediators of pain and fever, but also adaptive and protective reactions in many
      organs. A first step to reduce the overall toxicity and to increase the anti
      inflammatory activity of these drugs was achieved with the development of acidic
      'non-selective' (traditional) non-steroidal anti-inflammatory drugs (tNSAIDs).
      These agents distribute unequally throughout the body, reaching effective
      concentrations in inflamed tissue (effect compartment) for prolonged time
      periods. They can also reach effective concentrations in the bloodstream, kidney
      and gastrointestinal (GI) mucosa, where they can cause unwanted effects, such as
      GI toxicity, kidney dysfunction and cardiovascular impairment. All these effects
      are particularly prominent with compounds which are eliminated slowly [half-life
      (T((1/2))) >12 h] and thus also block prostaglandin production permanently
      outside the effect compartment. A second step towards improving safety was
      achieved with selective COX-2 inhibitors. These agents reduce the incidence of GI
      toxicity, pseudo-asthmatic reactions and blood loss following surgical
      interventions. However, they may be more toxic to the cardiovascular and renal
      systems than some tNSAIDs, possibly because they distribute homogeneously
      throughout the body and inhibit COX-2 in the endothelial layer of the vessels and
      the kidney permanently due to their slow elimination. Another step towards
      improvement in safety appears possible by combining both enzyme specificity and
      tissue selectivity, to achieve a further reduction of unwanted drug effects while
      maintaining the anti-inflammatory/analgesic efficacy.

PMID- 17459959
TI  - Synovial fibronectin fragmentation and domain expressions in relation to
      rheumatoid arthritis progression.
AB  - OBJECTIVE: To determine whether the expression of some fibronectin (FN) domains
      and a degree of FN degradation are associated with the progression of rheumatoid
      arthritis (RA). METHODS: Based on the radiographs of the hands of RA patients,
      three groups of synovial fluid and plasma samples were distinguished: (i) those
      with early radiological changes, (ii) established and (iii) late progressive
      radiological changes. The expressions of FN domains were determined by ELISA
      using appropriate domain-specific monoclonal antibodies. FN fragmentation was
      analysed by immunoblotting. RESULTS: In the early RA group, synovial FN was found
      to be totally degraded to a mixture of FN fragments. In the established group, it
      consisted of a portion of intact FN molecules and a smaller part of FN fragments,
      whereas in the late group the synovial FN immunoblotting pattern was similar to
      that of intact FN. The FN fragmentation was accompanied by decreases in FN immune
      reactivity with monoclonal antibodies specific to the collagen, fibrin and C
      terminal FN domains. In the blood plasma of all studied groups of RA patients,
      the FN immunopattern was analogous to that in normal plasma. However, the
      expressions of the plasma FN domains were higher than those of healthy
      individuals. CONCLUSIONS: Profound degradation of FN and low collagen, fibrin and
      C-terminal domain expressions in FN were only associated with early destructive
      changes observed in radiographs of the RA patients' hands.

PMID- 17459960
TI  - TFmodeller: comparative modelling of protein-DNA complexes.
AB  - Interactions between proteins and DNA molecules lie at the core of the
      fundamental cellular processes such as transcriptional regulation. Some of these
      interactions have been experimentally described at atomic scale, but the
      molecular details of many others remain to be discovered. TFmodeller exploits the
      current knowledge about protein-DNA interfaces contained in the Protein Data Bank
      and uses it to model similar interfaces related by homology. Results are emailed
      to the user and include an evolutionary contact matrix, a schematic
      representation of the putative binding interface and atomic coordinates of the
      modelled complex. The library of complexes used by TFmodeller is updated on a
      weekly basis and is available for download. AVAILABILITY: TFmodeller and its web
      service interface are free for academic users at
      http://www.ccg.unam.mx/tfmodeller.

PMID- 17459961
TI  - Murlet: a practical multiple alignment tool for structural RNA sequences.
AB  - MOTIVATION: Structural RNA genes exhibit unique evolutionary patterns that are
      designed to conserve their secondary structures; these patterns should be taken
      into account while constructing accurate multiple alignments of RNA genes. The
      Sankoff algorithm is a natural alignment algorithm that includes the effect of
      base-pair covariation in the alignment model. However, the extremely high
      computational cost of the Sankoff algorithm precludes its application to most RNA
      sequences. RESULTS: We propose an efficient algorithm for the multiple alignment
      of structural RNA sequences. Our algorithm is a variant of the Sankoff algorithm,
      and it uses an efficient scoring system that reduces the time and space
      requirements considerably without compromising on the alignment quality. First,
      our algorithm computes the match probability matrix that measures the
      alignability of each position pair between sequences as well as the base pairing
      probability matrix for each sequence. These probabilities are then combined to
      score the alignment using the Sankoff algorithm. By itself, our algorithm does
      not predict the consensus secondary structure of the alignment but uses external
      programs for the prediction. We demonstrate that both the alignment quality and
      the accuracy of the consensus secondary structure prediction from our alignment
      are the highest among the other programs examined. We also demonstrate that our
      algorithm can align relatively long RNA sequences such as the eukaryotic-type
      signal recognition particle RNA that is approximately 300 nt in length; multiple
      alignment of such sequences has not been possible by using other Sankoff-based
      algorithms. The algorithm is implemented in the software named 'Murlet'.
      AVAILABILITY: The C++ source code of the Murlet software and the test dataset
      used in this study are available at http://www.ncrna.org/papers/Murlet/.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 17459962
TI  - Mapping the genetic architecture of complex traits in experimental populations.
AB  - SUMMARY: Understanding how interactions among set of genes affect diverse
      phenotypes is having a greater impact on biomedical research, agriculture and
      evolutionary biology. Mapping and characterizing the isolated effects of single
      quantitative trait locus (QTL) is a first step, but we also need to assemble
      networks of QTLs and define non-additive interactions (epistasis) together with a
      host of potential environmental modulators. In this article, we present a full
      QTL model with which to explore the genetic architecture of complex trait in
      multiple environments. Our model includes the effects of multiple QTLs,
      epistasis, QTL-by-environment interactions and epistasis-by-environment
      interactions. A new mapping strategy, including marker interval selection,
      detection of marker interval interactions and genome scans, is used to evaluate
      putative locations of multiple QTLs and their interactions. All the mapping
      procedures are performed in the framework of mixed linear model that are flexible
      to model environmental factors regardless of fix or random effects being assumed.
      An F-statistic based on Henderson method III is used for hypothesis tests. This
      method is less computationally greedy than corresponding likelihood ratio test.
      In each of the mapping procedures, permutation testing is exploited to control
      for genome-wide false positive rate, and model selection is used to reduce ghost
      peaks in F-statistic profile. Parameters of the full-QTL model are estimated
      using a Bayesian method via Gibbs sampling. Monte Carlo simulations help define
      the reliability and efficiency of the method. Two real-world phenotypes (BXD
      mouse olfactory bulb weight data and rice yield data) are used as exemplars to
      demonstrate our methods. AVAILABILITY: A software package is freely available at
      http://ibi.zju.edu.cn/software/qtlnetwork

PMID- 17459963
TI  - GENOME: a rapid coalescent-based whole genome simulator.
AB  - SUMMARY: GENOME proposes a rapid coalescent-based approach to simulate whole
      genome data. In addition to features of standard coalescent simulators, the
      program allows for recombination rates to vary along the genome and for flexible
      population histories. Within small regions, we have evaluated samples simulated
      by GENOME to verify that GENOME provides the expected LD patterns and frequency
      spectra. The program can be used to study the sampling properties of any
      statistic for a whole genome study. AVAILABILITY: The program and C++ source code
      are available online at http://www.sph.umich.edu/csg/liang/genome/

PMID- 17459964
TI  - CTX-BLAST: context sensitive version of protein BLAST.
AB  - We present a software tool CTX-BLAST that incorporates contextual alignment model
      into the popular protein BLAST program. Our alignment tool allows us to
      investigate the effect of context-dependency in the protein alignment much more
      efficient than using previous dynamic algorithms. The software makes use of non
      symmetric contextual substitution tables and calculates the statistical
      significance of a given alignment according to the contextual statistical model.
      AVAILABILITY: CTX-BLAST is an open source software freely available from
      www.sourceforge.net/projects/CTX-BLAST. A program for statistical estimation of E
      value parameters and the contextual substitution table CTX-BLOSUM62 are also
      provided. SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 17459965
TI  - TOPD/FMTS: a new software to compare phylogenetic trees.
AB  - SUMMARY: TOPD/FMTS has been developed to evaluate similarities and differences
      between phylogenetic trees. The software implements several new algorithms
      (including the Disagree method that returns the taxa, that disagree between two
      trees and the Nodal method that compares two trees using nodal information) and
      several previously described methods (such as the Partition method, Triplets or
      Quartets) to compare phylogenetic trees. One of the novelties of this software is
      that the FMTS (From Multiple to Single) program allows the comparison of trees
      that contain both orthologs and paralogs. Each option is also complemented with a
      randomization analysis to test the null hypothesis that the similarity between
      two trees is not better than chance expectation. AVAILABILITY: The Perl source
      code of TOPD/FMTS is available at http://genomes.urv.es/topd.

PMID- 17459966
TI  - A multi-array multi-SNP genotyping algorithm for Affymetrix SNP microarrays.
AB  - MOTIVATION: Modern strategies for mapping disease loci require efficient
      genotyping of a large number of known polymorphic sites in the genome. The
      sensitive and high-throughput nature of hybridization-based DNA microarray
      technology provides an ideal platform for such an application by interrogating up
      to hundreds of thousands of single nucleotide polymorphisms (SNPs) in a single
      assay. Similar to the development of expression arrays, these genotyping arrays
      pose many data analytic challenges that are often platform specific. Affymetrix
      SNP arrays, e.g. use multiple sets of short oligonucleotide probes for each known
      SNP, and require effective statistical methods to combine these probe intensities
      in order to generate reliable and accurate genotype calls. RESULTS: We developed
      an integrated multi-SNP, multi-array genotype calling algorithm for Affymetrix
      SNP arrays, MAMS, that combines single-array multi-SNP (SAMS) and multi-array,
      single-SNP (MASS) calls to improve the accuracy of genotype calls, without the
      need for training data or computation-intensive normalization procedures as in
      other multi-array methods. The algorithm uses resampling techniques and model
      based clustering to derive single array based genotype calls, which are
      subsequently refined by competitive genotype calls based on (MASS) clustering.
      The resampling scheme caps computation for single-array analysis and hence is
      readily scalable, important in view of expanding numbers of SNPs per array. The
      MASS update is designed to improve calls for atypical SNPs, harboring allele
      imbalanced binding affinities, that are difficult to genotype without information
      from other arrays. Using a publicly available data set of HapMap samples from
      Affymetrix, and independent calls by alternative genotyping methods from the
      HapMap project, we show that our approach performs competitively to existing
      methods. AVAILABILITY: R functions are available upon request from the authors.

PMID- 17459968
TI  - p Value fetishism and use of the Bonferroni adjustment.

PMID- 17459967
TI  - Simultaneous and exact interval estimates for the contrast of two groups based on
      an extremely high dimensional variable: application to mass spec data.
AB  - MOTIVATION: Analysis of high-throughput proteomic/genomic data, in particular,
      surface-enhanced laser desorption/ionization time-of-flight mass spectrometry
      (SELDI-TOF MS) data and microarray data, has led to a multitude of techniques
      aimed at identifying potential biomarkers. Most of the statistical techniques for
      comparing two groups are based on qualitative measures such as P-value. A
      quantitative way such as interval estimation for the contrasts of two groups is
      more appealing. RESULTS: We have devised a simultaneous confidence bands method
      capable of detecting potential biomarkers, while controlling for overall
      confidence coverage level, in high-dimensional datasets that discriminate two
      treatment groups using a permutation scheme. For example, for the SELDI-TOF MS
      data, we deal with the entire spectrum simultaneously and construct (1 - alpha)
      confidence bands for the mean differences between groups. Furthermore, peaks were
      identified based on the maximal differences between the groups as determined by
      the confidence bands. The analysis method herein described gives both qualitative
      (P-value) and quantitative data (magnitude of difference). The Clinical
      Proteomics Programs Databank's ovarian cancer dataset and data from in-house
      samples containing known spiked-in proteins were analyzed. We were able to
      identify potential biomarkers similar to those described in previous analysis of
      the ovarian cancer data, however, while these markers are highly significant
      between cancer and normal groups, our analysis indicated the absolute difference
      between the two groups was minimal. In addition, we found additional markers than
      those previously described with greater differences in average intensities. The
      proposed confidence bands method successfully detected the spiked-in peaks, as
      well as, secondary peaks generated by adducts and double-charged species. We also
      illustrate our method utilizing paired gene expression data from a prostate
      cancer microarray experiment by constructing confidence bands for the fold
      changes between cancer and normal samples. AVAILABILITY: R-package, 'seie.zip'
      (license: GNU GPL), is publiclly available at
      http://research2.dfci.harvard.edu/dfci/MS_spike-in_data/

PMID- 17459969
TI  - Experimental interventions with sex offenders: a brief review of their efficacy.

PMID- 17459970
TI  - Intervention following deliberate self-harm: enough evidence to act?

PMID- 17459972
TI  - Remission one year after emergency admission is higher for substance-induced
      psychosis than primary psychosis.

PMID- 17459973
TI  - Significant and increasing depressive symptoms are associated with increased risk
      of new cardiac events in people with a heart attack in the previous year.

PMID- 17459974
TI  - Phobic anxiety and depression increase the risk of ventricular arrhythmias in
      people with coronary artery disease.

PMID- 17459975
TI  - The Child Trauma Screening Questionnaire predicts PTSD onset 6 months after
      traumatic accident better than the Children's Impact of Events Scale.

PMID- 17459976
TI  - Escitalopram 10 mg daily is more effective than paroxetine and placebo for
      generalised anxiety disorder.

PMID- 17459977
TI  - Review: little evidence to support dose escalation of selective serotonin
      reuptake inhibitors in non-responders.

PMID- 17459978
TI  - Decision support for primary care clinicians improves process of care but not
      symptoms in people with depression.

PMID- 17459979
TI  - Review: enhanced primary care programmes are effective for people with depression
      but are associated with increased healthcare costs.

PMID- 17459980
TI  - Benefits of bright light in non-seasonal major depression not sustained after
      discontinuation.

PMID- 17459981
TI  - Review: pharmacotherapy and psychotherapy similarly effective for depression in
      older adults.

PMID- 17459982
TI  - IMPACT collaborative care programme reduces suicide ideation in depressed older
      adults.

PMID- 17459983
TI  - Review: selective and indicated programmes are more effective than universal
      programmes for preventing depression in children and adolescents at 6 month
      follow-up.

PMID- 17459984
TI  - Review: evidence-based treatments are more effective than usual care for youths
      with psychological problems and maladaptive behaviour.

PMID- 17459985
TI  - Review: effects of behavioural parent training and cognitive-behavioural therapy
      on antisocial behaviour in children remain unclear.

PMID- 17459986
TI  - Brief cognitive-behavioural therapy reduces hospital readmission but does not
      reduce overall symptoms of schizophrenia.

PMID- 17459987
TI  - Quetiapine is no less effective than risperidone for reducing symptoms of
      schizophrenia.

PMID- 17459988
TI  - Clozapine improves symptoms but not quality of life compared with other second
      generation antipsychotics in people with treatment resistant schizophrenia.

PMID- 17459990
TI  - Oxcarbazepine is no more effective than placebo for reducing manic symptoms of
      bipolar I disorder in children and adolescents.

PMID- 17459989
TI  - Time to discontinuation similar for atypical antipsychotic drugs and placebo in
      people with Alzheimer's disease.

PMID- 17459991
TI  - Methylphenidate may improve symptoms but does not increase response compared with
      placebo in preschool children with ADHD.

PMID- 17459992
TI  - Cannabis use increases risk of developing symptoms of mania.

PMID- 17459993
TI  - Adolescent suicidal ideation predicts suicidal behaviour and psychopathological
      problems at age 30.

PMID- 17459994
TI  - Bipolar I disorder is common in first-degree relatives of children with
      prepubertal and early adolescent bipolar I disorder.

PMID- 17459995
TI  - Prevalence of non-fatal suicide attempts in black Americans is about 4%.

PMID- 17459996
TI  - Gestational age at delivery and Doppler waveforms in very preterm intrauterine
      growth-restricted fetuses as predictors of perinatal mortality.
AB  - OBJECTIVE: The aim of this study was to compare gestational age at delivery and
      the performance of middle cerebral artery (MCA), ductus venosus (DV), and
      umbilical artery Doppler parameters in the prediction of perinatal mortality and
      morbidity in intrauterine growth-restricted (IUGR) fetuses delivered at 32 weeks
      or earlier. METHODS: The study population consisted of 41 patients with IUGR
      fetuses. Delivery occurred for maternal or fetal indications. Two-tailed chi(2)
      and Fisher exact tests, an independent t test, and logistic regression were used
      for the analysis. P < .05 was considered statistically significant. RESULTS:
      Gestational age at delivery ranged between 23.1 and 32 weeks (median, 27.6
      weeks). There were 17 perinatal deaths. Ninety-four percent of the perinatal
      deaths occurred when the fetuses were delivered before 29 weeks. No fetus
      survived when delivered before 25 weeks. Two parameters predicted the perinatal
      mortality: gestational age at delivery (odds ratio, 0.52; 95% confidence
      interval, 0.31-0.88) and the combination of abnormal MCA peak systolic velocity +
      DV reversed flow (odds ratio, 10.2; 95% confidence interval, 1.8-57). For each
      week of pregnancy, there was a reduction in perinatal mortality of 48%. No
      Doppler parameters were significantly associated with perinatal morbidity.
      CONCLUSIONS: Gestational age at delivery and the combination of abnormal MCA peak
      systolic velocity + DV reversed flow in very preterm IUGR fetuses were the best
      parameters in predicting perinatal mortality. The decreased perinatal mortality
      that is found for each week IUGR fetuses remain in utero should be taken into
      account when a decision to deliver an IUGR fetus before 30 weeks is made.

PMID- 17459997
TI  - Fetal sex assignment by sonographic evaluation of the pelvic organs in the second
      and third trimesters of pregnancy.
AB  - OBJECTIVE: The purpose of this study was to determine the feasibility and
      reliability of fetal sex assignment by prenatal sonography of the pelvic organs
      in the second and third trimesters. METHODS: A prospective study, on an axial
      pelvic image with the umbilical arteries in cross section at the midpoint of the
      bladder, measured the distance between the posterior wall of the bladder and the
      anterior wall of the rectum. The bladder interface was scored as concave, flat,
      or convex. Endometrium visualization was recorded. A video loop of the pelvis was
      obtained. Each case was read by a second reader aware of only the gestational
      age. RESULTS: The study population included 205 fetuses. The primary reader was
      98.8% accurate in identifying true female fetuses and 100% accurate in
      identifying true male fetuses. The intraclass correlation coefficient for axial
      measurement was 0.99. Video loop analysis achieved 96% inter-reader concordance.
      In the second trimester, measurements in 100% of male fetuses were less than 3.3
      mm, and those in 94% of female fetuses were greater than 3.3 mm. In the third
      trimester, measurements in 96% of male fetuses were less than 4.7 mm, and those
      in 100% of female fetuses were greater than 4.7 mm. Ninety-eight percent of all
      fetuses with concave interfaces were female. The endometrium was visualized in
      74%. The additional time per examination was less than 5 minutes in 87.7%.
      CONCLUSIONS: Internal pelvic fetal sex assignment is a reliable additional method
      for fetal sex determination. A numerical discriminatory level can be used to
      distinguish between male and female internal genitalia. Larger numbers will be
      required to further refine these values.

PMID- 17459998
TI  - Nutcracker syndrome in children: the role of upright position examination and
      superior mesenteric artery angle measurement in the diagnosis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the pathophysiologic
      characteristics of nutcracker syndrome (NS) and to assess the role of upright
      position imaging and superior mesenteric artery (SMA) angle measurement in the
      diagnosis. METHODS: Doppler sonographic findings in 23 children with NS and in 26
      healthy control subjects were compared. The mesenteric angle, peak velocity (PV),
      and anteroposterior diameter of the left renal vein (LRV) at the hilar and
      aortomesenteric portions were measured in both the supine and upright positions.
      The means +/- SD of the SMA angle, anteroposterior diameter, and PV ratio between
      the two portions were calculated, and cutoff levels for the diagnosis of NS were
      established. RESULTS: The diameter and PV ratios were significantly different
      between the patient and control groups in both the supine and upright positions
      (P < .001). Differences between the supine and upright positions were also
      significant for the diameter of the LRV at the aortomesenteric portion, diameter
      ratio, and SMA angle in both groups. Upright position imaging revealed
      comparatively narrower SMA angles and more pronounced entrapment findings in
      patients with NS. The SMA angle measurement had sensitivity and specificity of
      69.6% and 61.5%, respectively, in the supine position and 87.0% and 76.9% in the
      upright position when the cutoff values were set to less than 41 degrees and 21
      degrees , respectively. CONCLUSIONS: The upright position has significant effects
      on the LRV hemodynamics and angle of the SMA in both patients and healthy
      subjects. Superior mesenteric artery angle measurement may be a useful adjunct
      parameter in the diagnosis of NS.

PMID- 17459999
TI  - Importance of sonographic detection of enlarged abdominal lymph nodes in
      children.
AB  - OBJECTIVE: Abdominal lymph nodes are frequently visualized by sonography in the
      pediatric population. The term "mesenteric lymphadenitis" is frequently used in
      the radiologic literature to describe this finding, whereas in the pediatric
      literature, this term is reserved for specific inflammation of the lymph nodes.
      The purpose of this study was to compare by sonography the incidence of
      appearance of enlarged abdominal lymph nodes (EALNs) in healthy children compared
      with that in children with abdominal pain of various causes. METHODS: In 200
      patients referred for abdominal sonography for various indications, the presence
      of EALNs, their location, and size were registered. The patients were divided
      into 3 groups: those with abdominal pain due to an acute abdominal condition
      (group 1), those with abdominal pain without an acute abdominal condition (group
      2), and asymptomatic patients (group 3). RESULTS: Enlarged abdominal lymph nodes
      greater than 5 mm were detected in 83.3% of group 1 patients, 73.8% of group 2
      patients, and 64% of group 3 patients. A significant statistical difference was
      found between patients with abdominal pain and asymptomatic children only for
      lymph nodes of 10 mm and larger (P = .0117). No statistically significant
      difference was seen in the presence of lymph node clusters between the patients
      with abdominal pain and asymptomatic children. There was a tendency of increased
      EALN occurrence with age, peaking at 10 years, with a decrease later.
      CONCLUSIONS: Enlarged abdominal lymph nodes are frequently encountered in
      asymptomatic children and should not always be considered abnormal. Enlarged
      abdominal lymph nodes exceeding 10 mm in their shortest axis in children with
      abdominal pain may represent mesenteric lymphadenitis of various causes.

PMID- 17460000
TI  - Sonographically guided core needle biopsy of cervical lymphadenopathy in patients
      without known malignancy.
AB  - OBJECTIVE: The purpose of this study was to retrospectively evaluate the efficacy
      of sonographically guided core needle biopsy (core biopsy) for diagnosing the
      causes of cervical lymphadenopathy in patients without known malignancy. METHODS:
      One hundred fifty-five sonographically guided core biopsies performed in 155
      patients with cervical lymphadenopathy were retrospectively evaluated. None of
      the 155 patients had any known primary malignancy. Final diagnoses were
      determined by the histologic examination from excision biopsy when performed or
      by the clinical and sonographic follow-up for more than 12 months. When a lymph
      node diagnosed as benign by sonographically guided core biopsy regressed
      spontaneously or by subsequent management, the diagnosis made by the
      sonographically guided core biopsy was considered correct. When a lymph node
      diagnosed as benign by sonographically guided core biopsy was unchanged or
      increased in size with subsequent management, excision biopsy was performed.
      Diagnostic yield, sensitivity, specificity, accuracy, and complications of core
      biopsy were evaluated. RESULTS: Histologic diagnosis could be made by
      sonographically guided core biopsy in 146 (94%) of the 155 patients. The
      histologic diagnoses were reactive hyperplasia in 44 patients, tuberculosis in
      37, Kikuchi disease in 25, metastasis in 16, lymphoma in 16, normal in 7, and
      toxoplasmosis in 1. Sensitivity, specificity, and accuracy of sonographically
      guided core biopsy were 97.9%, 99.1%, and 97.9%, respectively. There were no
      procedure-related complications. CONCLUSIONS: Sonographically guided core biopsy
      is a safe and efficient tool for diagnosing the cause of cervical lymphadenopathy
      in patients without known malignancy and may obviate unnecessary excisional
      biopsy.

PMID- 17460001
TI  - Paternity after varicocelectomy: preoperative sonographic parameters of success.
AB  - OBJECTIVE: This study was done to assess the sonographic findings that could
      predict the outcome of varicocele repair in the treatment of male
      infertility/subfertility related to varicocele. METHODS: This was a retrospective
      study and follow-up of 107 selected patients with male factor infertility related
      to the presence of varicocele. The patients were classified into 2 groups
      according to their estimated testicular size by sonography. Group 1 included 80
      patients with normal-sized testes (>15 cm(3)), and group 2 included 27 patients
      with small testes (10-15 cm(3)). The mean age +/- SD was 34 +/- 11 years. The
      mean duration of infertility was 3.4 +/- 1.4 years. They had oligospermia,
      asthenospermia, or oligoasthenospermia. The patients underwent low ligation
      varicocelectomy and were followed for 18 to 45 months after surgery for
      occurrence of paternity. Their scrotal sonographic findings were reviewed and
      correlated with the postoperative paternity rate. RESULTS: Postoperative
      paternity was achieved in 24 patients (30%) of group 1 with normal-sized testes
      and in 3 patients (11%) of group 2 with small testes. In patients of group 1, the
      positive paternity rate was higher (36.6%) in patients with clinically detected
      varicocele, compared with only 16% of patients with subclinical varicocele. In
      addition, postoperative paternity was significantly higher in patients with
      bilateral varicocele (54.5%; P = .0099), patients with shunt-type varicocele
      (75%; P = .0117), and patients with a permanent grade of venous reflux (70%; P =
      .0148). No significant differences were noted between positive paternity rates in
      patients with mildly or markedly dilated veins. CONCLUSIONS: The best
      preoperative sonographic parameters of success of varicocele repair are the
      presence of normal-sized testes, clinically palpable veins, bilateral varicocele,
      shunt-type varicocele, and a permanent grade of venous reflux. It does not matter
      how much the veins are dilated.

PMID- 17460002
TI  - Incidence of the retroaortic left renal vein in patients with varicocele.
AB  - OBJECTIVE: The purpose of this study was to investigate the incidence of the
      retroaortic left renal vein (RLRV) in patients with varicocele. METHODS: The left
      renal vein was ultrasonographically investigated for the presence of the RLRV in
      140 patients with varicocele and a control group of 137 age-matched patients. The
      main diagnostic criteria for varicocele were the presence of a varicose vein with
      a diameter of 3 mm or larger at rest and with a reflux lasting more than 2
      seconds during the Valsalva maneuver. The RLRV was defined as a posterior course
      of the left renal vein to the aorta at the level of the origin of the superior
      mesenteric artery. RESULTS: The RLRV was observed in 13 (9.3%) of the 140
      patients with varicocele and 3 (2.2%) of the control patients. The incidence of
      the RLRV was found to be significantly higher in patients with varicocele
      compared with the control patients (P = .018, Fisher exact test). In 13 patients
      with the RLRV, left varicocele and bilateral varicocele were detected in 10 and 3
      cases, respectively. CONCLUSIONS: In this study, the incidence of the RLRV was
      found to be significantly higher in patients with varicocele compared with
      control patients. Thus, we suggest that the presence of the RLRV may be
      considered one of the etiologic factors in the development of varicocele.

PMID- 17460003
TI  - Sonographic findings of groin masses.
AB  - OBJECTIVE: The groin contents consist of the spermatic cord and its fascial
      coverings and vascular, nervous, and muscular structures. Abnormalities in the
      groin region are variable. The purpose of this image presentation is to describe
      the sonographic findings of the various kinds of groin lesions. METHODS: We
      retrospectively reviewed the sonographic findings of various kinds of groin
      lesions. All sonographic examinations were performed with high-frequency (5- to
      15-MHz) linear array transducers. RESULTS: The most common abnormality in the
      groin was a hernia, which contains bowel loops, omental fat, and peritoneal
      fluid. The most common benign tumor of the inguinal region was a lipoma. Other
      benign tumors of the groin included leiomyomas, dermoid cysts, epidermoid cysts,
      and lymphangiomas. The most common primary malignant tumors in the inguinal
      region were sarcomas such as rhabdomyosarcoma and liposarcoma. Secondary
      malignant tumors of the inguinal regions were metastatic lymphomas and metastatic
      carcinomas of the lung, breast, ovary, and gastrointestinal tract. Hematomas and
      inflammation may occur in the inguinal region. CONCLUSIONS: Although there was
      substantial overlap of sonographic findings in the various inguinal masses,
      clinical history and certain sonographic details can assist in making the correct
      diagnosis.

PMID- 17460004
TI  - Complications of renal transplantation: ultrasonographic evaluation.
AB  - OBJECTIVE: The purpose of this presentation is to show the ultrasonographic
      findings of complications of renal transplantation. METHODS: We reviewed the
      ultrasonographic findings of complications of renal transplantation, including
      urologic complications, fluid collections, graft dysfunction, vascular
      complications, neoplasms, and recurrent native renal disease. RESULTS: Specific
      ultrasonographic features of complications of renal transplantation have been
      illustrated. CONCLUSIONS: Familiarity with the clinical setting and the
      appearance of potential renal transplant complications as depicted with the most
      commonly used modality, ultrasonography, will facilitate prompt, accurate
      diagnosis and treatment.

PMID- 17460005
TI  - Renal sonography with 2-dimensional versus cine organ imaging: preliminary
      results.
AB  - OBJECTIVE: This pilot study was undertaken to determine whether cine organ
      imaging (COI) of the entire kidney yields a quicker and equally diagnostic study
      compared with traditional 2-dimensional (2D) scanning. METHODS: Fifty-seven adult
      patients referred for diagnostic renal sonography underwent 2D sonography
      followed by COI performed by a second sonographer, who was blinded to the results
      of the first examination. Images were interpreted blindly by 2 independent
      readers in 2 separate reading sessions divided into 2D or COI image sets for each
      patient. The acquisition time and interpretation time of each protocol were
      recorded. Images were scored for the percentage of kidney visualized and for the
      presence or absence of hydronephrosis, stones, cysts, and renal lesions (non
      simple cysts and solid masses). RESULTS: The average acquisition time decreased
      from 13.3 to 10.5 minutes between 2D and COI studies, respectively (P = .02). The
      average image interpretation time increased 37 seconds (P < .0001). A greater
      percentage of parenchymal visualization was achieved with COI versus 2D imaging.
      There was no significant difference in detection of renal abnormalities
      (hydronephrosis, stones, renal cysts, and masses) between the 2 modes, although
      the detection of cysts on COI was equal to or greater than that on 2D imaging on
      a per-patient basis. CONCLUSIONS: Cine organ imaging decreased the acquisition
      time significantly while retaining and possibly improving diagnostic quality. The
      minimally increased interpretation time may be decreased in the future by fewer
      volume acquisitions per patient. Further investigations will be needed to assess
      the impact of color Doppler imaging in volumetric protocols as well as to compare
      renal lesion detection versus computed tomography and magnetic resonance imaging.

PMID- 17460006
TI  - Automated ultrasound scanning on a dual-modality breast imaging system: coverage
      and motion issues and solutions.
AB  - OBJECTIVE: We are developing an automated ultrasound imaging-mammography system
      wherein a digital mammography unit has been augmented with a motorized ultrasound
      transducer carriage above a special compression paddle. Challenges of this system
      are acquiring complete coverage of the breast and minimizing motion. We assessed
      these problems and investigated methods to increase coverage and stabilize the
      compressed breast. METHODS: Visual tracings of the breast-to-paddle contact area
      and breast periphery were made for 10 patients to estimate coverage area. Various
      motion artifacts were evaluated in 6 patients. Nine materials were tested for
      coupling the paddle to the breast. Fourteen substances were tested for coupling
      the transducer to the paddle in lateral-to-medial and medial-to-lateral views and
      filling the gap between the peripheral breast and paddle. In-house image
      registration software was used to register adjacent ultrasound sweeps. RESULTS:
      The average breast contact area was 56%. The average percentage of the peripheral
      air gap filled with ultrasound gel was 61%. Shallow patient breathing proved
      equivalent to breath holding, whereas speech and sudden breathing caused
      unacceptable artifacts. An adhesive spray that preserves image quality was found
      to be best for coupling the breast to the paddle and minimizing motion. A highly
      viscous ultrasound gel proved most effective for coupling the transducer to the
      paddle for lateral-to-medial and medial-to-lateral views and for edge fill-in.
      CONCLUSIONS: The challenges of automated ultrasound scanning in a multimodality
      breast imaging system have been addressed by developing methods to fill in
      peripheral gaps, minimize patient motion, and register and reconstruct multisweep
      ultrasound image volumes.

PMID- 17460007
TI  - Penile compartment syndrome: a possible explanation for penile pain in peyronie
      disease shown by penile sonography.
AB  - OBJECTIVE: Our purpose was to describe sonographic findings in patients with
      Peyronie disease that may explain persistent penile pain in these patients. We
      propose the term penile compartment syndrome for use in radiology and urology
      practice to describe this condition. METHODS: Thirty-five consecutive patients
      were examined. All these patients had clinically "mature" plaques with Peyronie
      disease. Penile duplex sonography was performed as part of the patient evaluation
      before possible corrective surgery. RESULTS: All patients had the classic
      sonographic finding of plaques in the tunica albuginea. Persistent venous
      insufficiency was noted in 3 patients (8.6%); we observed arterial insufficiency
      during dynamic evaluation of blood flow in 2 (5.8%); and in 2 cases, a low peak
      systolic velocity was accompanied by an abnormal cavernous artery structure. Four
      patients (11.4%) had extensive circular plaques in the tunica albuginea, limiting
      expansion of the cavernous body during erection, as shown by a constant cavernous
      body diameter of the affected side compared with an increasing diameter of the
      unaffected side during the progressive phases of erection. Patients with a
      constricting ring of plaques had persistent penile pain during erection as well
      as after injection during penile duplex sonography. CONCLUSIONS: Peyronie disease
      is caused by replacement of penile tunica albuginea tissue with inelastic
      scarring. One manifestation of Peyronie disease is painful erection. In patients
      with persistent erectile pain, we found circumferential inelastic scarring of the
      tunica albuginea. The findings of penile compartment syndrome on penile
      sonography may influence the urologist's choice of surgical technique for
      treating Peyronie disease.

PMID- 17460008
TI  - Characteristic sonographic findings of hepatic erosion by umbilical vein
      catheters.
AB  - OBJECTIVE: The purpose of this series is to describe findings seen on abdominal
      sonography in neonates with erosion into the liver by umbilical vein catheters
      (UVCs). METHODS: Four neonates with erosion of the UVC into hepatic parenchyma
      within a 2-year period were identified. A retrospective case analysis was
      performed to determine the symptoms and clinical scenario of presentation. Plain
      radiographs were examined to establish the location of the UVC placement, and
      abdominal sonograms were reviewed. RESULTS: All 4 neonates had abdominal
      distension within 9 days of UVC placement, and in all of them, the UVC tip was
      located below the hemidiaphragm and superimposed over the liver. Sonographic
      examination of all patients showed intraparenchymal liver lesions with an
      echogenic rim and hypoechoic center. Two neonates also had subcapsular fluid
      collections. Complex ascites was seen in all 4 patients. The fluid was proven to
      be total parenteral nutrition by paracentesis in 2 patients. Treatment consisted
      of removal of the UVC. All patients were followed for a period of 2 to 18 months
      and showed clinical resolution of symptoms or sonographic improvement of the
      liver lesions. CONCLUSIONS: A characteristic liver lesion can be seen on
      sonography with hepatic erosion by UVCs. Our study shows the importance of a high
      index of suspicion of UVC erosion into the liver in neonates with catheters
      positioned in the liver. When such neonates have abdominal distension, prompt
      abdominal sonograms should be obtained.

PMID- 17460009
TI  - Color Doppler imaging and 3-dimensional sonographic findings of urinary bladder
      leiomyoma.

PMID- 17460010
TI  - Tuberculous epididymo-orchitis after intravesical BCG therapy for superficial
      bladder carcinoma: sonographic findings.

PMID- 17460011
TI  - Occult testicular teratoma presenting with solid mesenteric metastasis.

PMID- 17460012
TI  - Use of emergency musculoskeletal sonography in diagnosis of an open fracture of
      the hand.

PMID- 17460013
TI  - Ultrasonographic findings in isolated neuritis of the posterior interosseous
      nerve: comparison with normal findings.

PMID- 17460014
TI  - Mesenchymal dysplasia in a monochorionic diamniotic twin pregnancy with review of
      the differential diagnosis of cystic changes in the placenta.

PMID- 17460015
TI  - Expedited oxygen wean after coil embolization of systemic-to-pulmonary
      collaterals in a premature infant with bronchopulmonary dysplasia.

PMID- 17460016
TI  - Absent infrarenal inferior vena cava: an unusual cause of pelvic varices.

PMID- 17460017
TI  - Extracorporeal ablation of uterine fibroids with high-intensity focused
      ultrasound.

PMID- 17460018
TI  - Preventing ventricular dysfunction in pacemaker patients without advanced heart
      failure: rationale and design of the PREVENT-HF study.
AB  - AIMS: Right ventricular (RV) pacing has been shown to cause heart failure
      symptoms in patients with and without previous systolic left ventricular (LV)
      dysfunction. The aim here was to evaluate the preventive effect of biventricular
      pacing vs. RV apical pacing in patients with indication for permanent ventricular
      pacing. Methods PREVENT-HF is an ongoing multicentre randomized controlled pilot
      study designed to assess whether biventricular pacing is superior to RV pacing in
      patients receiving a bradycardia pacemaker for standard indications. Patients
      with Class I or IIa indication according to ACC/AHA guidelines for cardiac pacing
      judged likely to require high (>or=80%) ventricular pacing are randomized to
      receive either RV or biventricular stimulation. Patients are ineligible if
      younger than 18 years, have Class III or IV heart failure, or experienced a
      recent myocardial infarction or cardiac surgery. Echocardiographic parameters of
      LV function are assessed at baseline, 6 months, and 12 months. The primary
      endpoint is change in LV end diastolic volume. Secondary outcomes include LV
      ejection fraction, mortality, morbidity, and mitral regurgitation. In subsets of
      patients, NT-pro-BNP and oxygen uptake are analysed. Centres in Spain (five),
      Italy (four), and Germany (seven) will enrol 100 patients. CONCLUSION: PREVENT-HF
      will contribute to better define the role of chronic biventricular pacing for
      advanced atrioventricular block.

PMID- 17460019
TI  - Local health policy development processes in the Netherlands: an expanded toolbox
      for health promotion.
AB  - Although much research has been done on the existence and formation of risk and
      issue based health policies, there is only little insight in health policy
      development processes in a broader context. This hampers intervention in these
      policy processes to adequately develop integrated and effective health policies.
      Legislation in the Netherlands requires municipalities to develop and implement
      local health policies. These policies are supposed to aim at the promotion of
      health across sectors and with a strong community involvement. Health policy
      development processes have been studied in four Dutch municipalities. For each
      case, we identified a range of stakeholders and monitored the change or stability
      of their characteristics over 3 years. In addition, for each case, three
      overlaying maps of networks were made addressing communication and collaboration
      actions within the defined set of stakeholders. We point out a number of barriers
      which impede integrated policy development at the local level: the importance
      given to local health policy, the medical approach to health development, the
      organizational self-interest rather than public health concern, the absence of
      policy entrepreneurial activity. Furthermore, this article advocates the use of
      complementary theoretical frameworks and the expansion of the methodological
      toolbox for health promotion. The value of stakeholder and network analysis in
      the health promotion domain, at this stage, is two-fold. First, mapping relevant
      actors, their positions and connections in networks provides us with insight into
      their capacity to participate and contribute to health policy development.
      Second, these new tools contribute to a further understanding of policy
      entrepreneurial roles to be taken up by health promotion professionals and health
      authorities in favour of the socio-environmental approach to health.
      Notwithstanding the value of this first step, more research is required into both
      the practical application as well as in the theoretical connections with, for
      example, Multiple Streams theory.

PMID- 17460021
TI  - Nosocomial infection in small for gestational age newborns with birth weight
      <1500 g: a multicentre analysis.
AB  - OBJECTIVE: To investigate whether preterm newborns who are small for gestational
      age are at increased risk of nosocomial infections and necrotising enterocolitis.
      DESIGN, SETTING AND SUBJECTS: The German national surveillance system for
      nosocomial infection in very low birthweight infants uses the US Centers for
      Disease Control and Prevention criteria. 2918 newborns (24-28 weeks), born
      between 2000 and 2004, were selected after application of predefined inclusion
      criteria to ensure similar proportions of small and appropriate weight for
      gestational age newborns across gestational age groups. MAIN OUTCOME MEASURES:
      The outcome criterion was at least one episode of nosocomial sepsis, pneumonia or
      necrotising enterocolitis. Adjusted odds ratios and corresponding 95% CIs were
      calculated based on general estimating equation models. RESULTS: The study
      population consisted of 13% (n = 392) small and 87% (n = 2526) appropriate weight
      for gestational age infants. 33% (n = 950) of the infants experienced at least
      one episode of sepsis: 42% (n = 163) of small and 31% (n = 787) of appropriate
      weight for gestational age newborns (adjusted OR 1.41, 95% CI 1.05 to 1.89).
      Pneumonia was diagnosed in 6% (n = 171) of infants: 8.4% (n = 33) of small and
      5.5% (n = 138) of appropriate weight for gestational age newborns (adjusted OR
      1.57, 95% CI 1.19 to 5.57). Necrotising enterocolitis was documented in 5.2% (n =
      152) of infants: 7.1% (n = 28) of small and 4.9% of (n = 124) appropriate weight
      for gestational age newborns (adjusted OR 1.20, 95% confidence interval 0.75 to
      1.94). CONCLUSIONS: Growth-retarded preterm infants seem to be at increased risk
      of nosocomial infection, irrespective of the responsible pathogen. Future
      immunological research should elucidate potential causal associations.

PMID- 17460022
TI  - Cardiorespiratory effects of changes in end expiratory pressure in ventilated
      newborns.
AB  - BACKGROUND: Positive pressure ventilation in premature infants can improve
      oxygenation but may diminish cerebral blood flow and cardiac output. Low superior
      vena cava (SVC) flow increases risk of intraventricular haemorrhage, and higher
      mean airway pressure is associated with low SVC flow. Whether this is a direct
      effect of positive pressure ventilation or a reflection of severity of lung
      disease is not known. This study aimed to determine if positive end expiratory
      pressure (PEEP) in ventilated newborns could be increased without clinically
      relevant cardiorespiratory changes. METHOD: Ventilated newborns were studied
      before and 10 min after increasing PEEP (5 cm H(2)O to 8 cmH(2)O) and again when
      PEEP returned to baseline. Echocardiographic and respiratory function
      measurements were collected during the intervention. RESULTS: In 50 infants,
      increased PEEP was associated with a non-significant difference in mean SVC flow
      of -5 ml/kg/min (95% CI -12 to 3 ml/kg/min) but a significant reduction in right
      ventricular output of 17 ml/kg/min (95% CI 5 to 28 ml/kg/min). The increase in
      lung compliance was non-significant (median difference 0.02 ml/cmH(2)O/kg) and
      the decrease in lung resistance (18 cmH(2)O/l/s; 95% CI 10 to 26 cm H(2)O/l/s)
      was significant. Changes (%) in lung compliance and SVC flow, when corrected for
      Paco(2), were positively associated (regression coefficient 0.4%; 95% CI 0.2% to
      0.6%). CONCLUSION: A short-term increase in PEEP does not lead to significant
      changes in systemic blood flow, although 36% of infants in the present study had
      clinically important changes in flow (+/-25%). The intervention can improve
      dynamic lung function, especially airway resistance. Improvements in compliance
      tend to be associated with improvements in blood flow.

PMID- 17460023
TI  - Selective fluconazole prophylaxis in high-risk babies to reduce invasive fungal
      infection.
AB  - OBJECTIVES: To evaluate the impact of selective fluconazole prophylaxis on
      incidence of invasive fungal infection and emergence of fluconazole resistance in
      neonatal intensive care. DESIGN: Retrospective study of very low birthweight
      (VLBW) babies (<1500 g birth weight) admitted to a neonatal intensive care unit
      (NICU) in the period 1 year before and after the implementation of an antifungal
      prophylaxis guideline. PATIENTS: VLBW babies with an additional risk factor:
      colonisation of Candida species from surface sites with a central venous
      catheter; third generation cephalosporin treatment; or total duration of
      antibiotic treatment >10 days. Fluconazole protocol: Fluconazole 6 mg/kg for 3
      weeks. Dose interval is every 72 h during the first 2 weeks of life. Thereafter,
      dose interval is reduced to every 48 h until 3 weeks old when daily fluconazole
      is given. Fluconazole is administered orally when enteral feeding achieved.
      RESULTS: 121 and 107 VLBW babies were admitted to the NICU in the year before and
      after the guideline was implemented, respectively. Data were available in 110 and
      102 charts. 33/110 and 31/102 babies were eligible for fluconazole prophylaxis in
      the period before and after guideline implementation. 6/33 babies eligible for
      prophylaxis developed culture proven Candida sepsis before compared with no
      (0/31) babies after the guideline was implemented (p = 0.03). One baby (1/31) did
      develop probable Candida sepsis in the post guideline implementation period.
      During both study periods all Candida isolates remained fully susceptible to
      fluconazole. CONCLUSIONS: Selective antifungal prophylaxis has reduced invasive
      fungal sepsis in one NICU without evidence of fluconazole resistance emerging.

PMID- 17460024
TI  - Does treatment of newly diagnosed idiopathic thrombocytopenic purpura reduce
      morbidity?
AB  - AIM: To explore whether early treatment of children with idiopathic
      thrombocytopenic purpura (ITP) with immunoglobulin and/or corticosteroids reduces
      subsequent morbidity. METHODS: Centres participating in a Nordic ITP study were
      divided according to whether they had treated more than 2/3, from 1/3 to 2/3, or
      less than 1/3 children within 14 days of diagnosis. The course of disease from 15
      days to 6 months after diagnosis was compared for children managed at the three
      centre categories. The comparison was restricted to children in whom at least one
      platelet count <20x10(9)/l was measured, numbering 156, 143 and 84 in the three
      different categories, respectively. RESULTS: The three groups of children were
      clinically similar but were managed with initial treatment rates of 89%, 57% and
      14%, respectively. By day 15, the platelet count had stabilised to >20x10(9)/l in
      67%, 67% and 52% (p<0.05) and to >150x10(9)/l in 38%, 29% and 29% (p<0.20). At 1
      month after diagnosis there was no difference in recovery rates. Chronic ITP
      developed in 27%, 22% and 25% in the three groups. During follow-up, one or more
      disease-related events occurred in 23%, 22% and 19%, with no difference in the
      average numbers of episodes with mucosal bleeding. Treatment courses were
      administered to 19%, 13% and 11%, respectively. CONCLUSION: Active treatment
      policies accelerated platelet recovery in children with short-lasting ITP but did
      not avert the development of chronic ITP and did not cause a reduction in
      morbidity during follow-up.

PMID- 17460025
TI  - Deep brain stimulation in childhood: an effective treatment for early onset
      idiopathic generalised dystonia.
AB  - BACKGROUND: Early onset idiopathic generalised dystonia is a progressive and
      profoundly disabling condition. Medical treatment may ameliorate symptoms.
      However, many children have profound, intractable disability including the loss
      of ambulation and speech, and difficulties with feeding. Following the failure of
      medical management, deep brain stimulation (DBS) of the globus pallidus internus
      (GPi) has emerged as an alternative treatment for the disorder. METHODS: We
      describe four children who presented with dystonia. RESULTS: Following the
      failure of a range of medical therapies, DBS systems were implanted in the GPi in
      an attempt to ameliorate the children's disabilities. All children found dystonic
      movements to be less disabling following surgery. Compared with preoperative
      Burke, Fahn and Marsden Dystonia Rating Scale scores, postoperative scores at 6
      months were improved. CONCLUSIONS: DBS is effective in improving symptoms and
      function in children with idiopathic dystonia refractory to medical treatment.
      Whilst surgery is complex and can be associated with intraoperative and
      postoperative complications, this intervention should be considered following the
      failure of medical therapy.

PMID- 17460026
TI  - BSAC standardized disc susceptibility testing method (version 6).

PMID- 17460027
TI  - Presence of plasmid pA15 correlates with prevalence of constitutive MLS(B)
      resistance in group A streptococcal isolates at a university hospital in southern
      Taiwan.
AB  - OBJECTIVES: To investigate the role of a plasmid bearing the erm(B) gene on the
      prevalence of the macrolide, lincosamide and group B streptogramin (MLS(B))
      phenotype of group A streptococci (GAS) and to characterize the plasmid and
      determine the clonal relation between the erythromycin-resistant isolates.
      METHODS: Two hundred and five erythromycin-resistant GAS isolates were collected
      from 1990 to 2006. Colony hybridization, PCR, plasmid curing and PFGE techniques
      were used to analyse the mechanisms behind the phenotypes. RESULTS: Among the 56
      isolates with constitutive MLS(B) (cMLS(B)) resistance, 53 isolates harboured a
      plasmid, pA15, of 19 kb. erm(B) was on pA15 and it confered a cMLS(B) resistance
      phenotype. The prevalence rate of the pA15-containing isolates was 36.3% from
      1993 to 1995, but the plasmid could not be detected from 2004 to 2006. To link
      the high-level resistance to pA15, clinical isolate A15 was selected and pA15 was
      cured by novobiocin. In the plasmid-cured strain SW503, the erythromycin MIC
      decreased from 256 to 0.032 mg/L. By electroporation, pA15 was re-introduced into
      the plasmid-cured erythromycin-susceptible strain, and the high-level
      erythromycin resistance was restored. Plasmid pA15 was also transferred to group
      B streptococci and group C streptococci by electroporation. In all the pA15
      containing isolates, emm1 type was present and pulse type J was predominant (48
      of 54 isolates). CONCLUSIONS: The plasmid pA15 mediated cMLS(B) resistance in the
      mid-1990s, but pA15 was not detected in the clinical isolates from 2004 onwards,
      which correlates with the absence of cMLS(B) resistance in this region.

PMID- 17460028
TI  - Identification of metabolites of 4-nonylphenol isomer 4-(3',6'-dimethyl-3'
      heptyl) phenol by rat and human liver microsomes.
AB  - Nonylphenol (NP) has been widely used for more than 50 years in the synthesis of
      NP ethoxylates, which are important nonionic surfactants. NP is considered an
      endocrine disruptor based on in vitro and in vivo animal studies. However, the
      toxic effects of NP in humans are unknown. Information regarding the metabolic
      fate of 4-t-nonylphenol (4-tNP), a mixture of commercial NP branched isomers, in
      mammalian species is limited. This information is critical for the identification
      of adequate biomarkers of exposure to NP that could be used for exposure and risk
      assessment. We identified metabolites of one 4-tNP isomer, namely, 4-(3',6'
      dimethyl-3'-heptyl) phenol (P363-NP), using rat and human liver microsomes. The
      P363-NP metabolites were extracted by on-line solid-phase extraction and then
      separated and detected using high-performance liquid chromatography/tandem mass
      spectrometry. Using the genuine standard, we unambiguously identified 4-(3',6'
      dimethyl-3'-heptyl) catechol (P363-NC) as the main P363-NP metabolite when using
      human liver microsomes. Based on their chromatographic behavior and mass spectral
      fragmentation patterns, several other metabolites were tentatively identified,
      including a hydroxylated P363-NP with the alcohol functional group on the
      branched alkyl chain and its oxidative metabolite, a catechol with a hydroxylated
      alkyl side chain. Furthermore, the metabolite profile of P363-NP using rat and
      human enzymes was compared. Our findings suggest that P363-NC could be used as a
      biomarker to assess exposure to 4-tNP, although additional research to evaluate
      its suitability as a biomarker is warranted.

PMID- 17460029
TI  - A natural variant of the heme-binding signature (R441C) resulting in complete
      loss of function of CYP2D6.
AB  - A new variant allele CYP2D6*62 (g.4044C>T; R441C) of the drug-metabolizing
      cytochrome P450 (P450) CYP2D6 was identified in a person with reduced sparteine
      oxidation phenotype, which was unexpected based on a genetic CYP2D6*1A/*41
      background. The recombinantly expressed variant protein had no activity toward
      propafenone as a result of missing heme incorporation. Sequence alignment
      revealed that the positively charged R441 residue is part of the heme-binding
      signature but not strictly conserved among all the P450s. A compilation of
      described P450 monooxygenase variants revealed that other enzymes can
      functionally tolerate even nonconservative amino acid changes at the
      corresponding position (i.e., the invariant cysteine 2). This suggests that heme
      binding in mammalian P450s depends not only on the integrity of the heme-binding
      signature but also on other family- and subfamily-specific sequence determinants.

PMID- 17460030
TI  - Mutation of a single residue (K262R) in P450 2B6 leads to loss of mechanism-based
      inactivation by phencyclidine.
AB  - Human cytochrome P450 (P450) 2B6 plays an important role in the metabolism of
      many drugs used in the clinic, and it has been shown to be highly polymorphic and
      inducible by a variety of substrates. The metabolism of phencyclidine (PCP) by
      P450 2B6 results in mechanism-based inactivation of the enzyme. We investigated
      the effects of a naturally occurring mutation of P450 2B6 where a lysine 262 is
      changed to an arginine (K262R) on PCP metabolism and mechanism-based inactivation
      of 2B6 by PCP. The K262R mutant retained the 7-ethoxy-4-trifluoromethylcoumarin O
      deethylation activity when it was incubated with PCP and NADPH in the
      reconstituted system, whereas the wild-type enzyme was readily inactivated by
      PCP. Spectral binding studies showed that PCP was reversibly bound in the active
      site of the K262R mutant with slightly higher affinity (156 muM) compared with
      the wild-type 2B6 (397 muM). In addition, all the metabolites of PCP (M1-M8) that
      were formed by the wild-type enzyme were also formed by the K262R mutant.
      Although the K262R mutant metabolized PCP to give similar metabolite profiles,
      the overall rate of metabolite formation was lower than the wild-type enzyme. A
      reactive intermediate of PCP was formed by wild-type P450 2B6 and trapped with
      glutathione (GSH). However, no GSH conjugates were detected from incubations with
      the K262R mutant. These data suggest that the lysine 262 residue plays an
      important role in the formation of a reactive intermediate of PCP that leads to
      the mechanism-based inactivation of P450 2B6.

PMID- 17460031
TI  - Cytochrome P450 3A-dependent metabolism of a potent and selective gamma
      aminobutyric acid Aalpha2/3 receptor agonist in vitro: involvement of cytochrome
      P450 3A5 displaying biphasic kinetics.
AB  - In vitro metabolism studies were conducted to determine the human cytochrome P450
      enzyme(s) involved in the biotransformation of 7-(1,1-dimethylethyl)-6-(2-ethyl
      2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3b]pyridazine
      (TPA023), a selective agonist of human gamma-aminobutyric acid(A) receptor alpha2
      and alpha3 subunits. Incubation of TPA023 with NADPH-fortified human liver
      microsomes resulted in the formation of t-butyl hydroxy TPA023, N-desethyl
      TPA023, and three minor metabolites. Both t-butyl hydroxylation and N
      deethylation reactions were greatly inhibited (>85%) in the presence of CYP3A
      selective inhibitory antibodies and chemical inhibitors, indicating that members
      of the CYP3A subfamily play an important role in TPA023 metabolism. Eadie-Hofstee
      plots of t-butyl hydroxylation and N-deethylation in pooled CYP3A5-rich human
      liver microsomes revealed a low K(m) (3.4 and 4.5 microM, respectively) and a
      high K(m) (12.7 and 40.0 microM, respectively) component. For both metabolites,
      the high K(m) component was not observed with a pool of microsomal preparations
      containing minimal levels of CYP3A5. Preincubation of liver microsomes with
      mifepristone (selectivity for CYP3A4 > CYP3A5) greatly inhibited both t-butyl
      hydroxylation and N-deethylation (>75%); however, the residual activities were
      significantly higher in the pooled CYP3A5-rich liver microsomes (p < 0.0005). In
      addition, elevated levels of residual t-butyl hydroxylase and N-deethylase
      activities were observed in the presence of both CYP3A5-rich and CYP3A5-deficient
      preparations when the substrate concentration increased from 4 to 40 microM. In
      agreement, metabolite formation catalyzed by recombinant CYP3A5 was described by
      a biphasic model. It is concluded that CYP3A4 plays a major role in TPA023
      metabolism, and CYP3A5 may also contribute at higher concentrations of the
      compound.

PMID- 17460033
TI  - Costimulation blockade--what will the future bring?

PMID- 17460034
TI  - Pandemic influenza: studying the lessons of history.

PMID- 17460035
TI  - Nitric oxide mediates prostaglandins' deleterious effect on lipopolysaccharide
      triggered murine fetal resorption.
AB  - Genital tract bacterial infections could induce abortion and are some of the most
      common complications of pregnancy; however, the mechanisms remain unclear. We
      investigated the role of prostaglandins (PGs) in the mechanism of bacterial
      lipopolysaccharide (LPS)-induced pregnancy loss in a mouse model, and we
      hypothesized that PGs might play a central role in this action. LPS increased PG
      production in the uterus and decidua from early pregnant mice and stimulated
      cyclooxygenase (COX)-II mRNA and protein expression in the decidua but not in the
      uterus. We also observed that COX inhibitors prevented embryonic resorption (ER).
      To study the possible interaction between nitric oxide (NO) and PGs, we
      administered aminoguanidine, an inducible NO synthase inhibitor. NO inhibited
      basal PGE and PGF(2alpha) production in the decidua but activated their uterine
      synthesis and COX-II mRNA expression under septic conditions. A NO donor (S
      nitroso-N-acetylpenicillamine) produced 100% ER and increased PG levels in the
      uterus and decidua. LPS-stimulated protein nitration was higher in the uterus
      than in the decidua. Quercetin, a peroxynitrite scavenger, did not reverse LPS
      induced ER. Our results suggest that in a model of septic abortion characterized
      by increased PG levels, NO might nitrate and thus inhibit COX catalytic activity.
      ER prevention by COX inhibitors adds a possible clinical application to early
      pregnancy complications due to infections.

PMID- 17460036
TI  - Functional, structural, and spectroscopic characterization of a glutathione
      ligated [2Fe-2S] cluster in poplar glutaredoxin C1.
AB  - When expressed in Escherichia coli, cytosolic poplar glutaredoxin C1 (CGYC active
      site) exists as a dimeric iron-sulfur-containing holoprotein or as a monomeric
      apoprotein in solution. Analytical and spectroscopic studies of wild-type protein
      and site-directed variants and structural characterization of the holoprotein by
      using x-ray crystallography indicate that the holoprotein contains a subunit
      bridging [2Fe-2S] cluster that is ligated by the catalytic cysteines of two
      glutaredoxins and the cysteines of two glutathiones. Mutagenesis data on a
      variety of poplar glutaredoxins suggest that the incorporation of an iron-sulfur
      cluster could be a general feature of plant glutaredoxins possessing a glycine
      adjacent to the catalytic cysteine. In light of these results, the possible
      involvement of plant glutaredoxins in oxidative stress sensing or iron-sulfur
      biosynthesis is discussed with respect to their intracellular localization.

PMID- 17460037
TI  - The generation of influenza outbreaks by a network of host immune responses
      against a limited set of antigenic types.
AB  - It is commonly believed that influenza epidemics arise through the incremental
      accumulation of viral mutations, culminating in a novel antigenic type that is
      able to escape host immunity. Successive epidemic strains therefore become
      increasingly antigenically distant from a founding strain. Here, we present an
      alternative explanation where, because of functional constraints on the defining
      epitopes, the virus population is characterized by a limited set of antigenic
      types, all of which may be continuously generated by mutation from preexisting
      strains and other processes. Under these circumstances, influenza outbreaks arise
      as a consequence of host immune selection in a manner that is independent of the
      mode and tempo of viral mutation. By contrast with existing paradigms, antigenic
      distance between epidemic strains does not necessarily accumulate with time in
      our model, and it is the changing profile of host population immunity that
      creates the conditions for the emergence of the next influenza strain rather than
      the mutational capabilities of the virus.

PMID- 17460038
TI  - Small-molecule synergist of the Wnt/beta-catenin signaling pathway.
AB  - The Wnt/beta-catenin signaling pathway regulates cell fate and behavior during
      embryogenesis, adult tissue homeostasis, and regeneration. When inappropriately
      activated, the pathway has been linked to colorectal cancer and melanoma, and
      when attenuated it may contribute to Alzheimer's disease and osteoporosis. Small
      molecules that modulate Wnt signaling will likely provide new insights into the
      regulation of this key developmental pathway and ultimately provide
      pharmacological agents to control Wnt signaling in vivo. To this end, we screened
      a library of 100,000 small molecules for activity in a cell-based assay of
      Wnt/beta-catenin signaling and discovered a purine derivative, QS11, that
      synergizes with Wnt-3a ligand in the activation of Wnt/beta-catenin signal
      transduction. Through affinity chromatography and subsequent functional assays,
      we showed that QS11 binds and inhibits the GTPase activating protein of ADP
      ribosylation factor 1 (ARFGAP1), suggesting that QS11 modulates Wnt/beta-catenin
      signaling through an effect on protein trafficking. Consistent with its function
      as an ARFGAP inhibitor, QS11 inhibits migration of ARFGAP overexpressing breast
      cancer cells.

PMID- 17460039
TI  - KSper, a pH-sensitive K+ current that controls sperm membrane potential.
AB  - Mature mammalian spermatozoa are quiescent in the male reproductive tract. Upon
      ejaculation and during their transit through the female reproductive tract, they
      undergo changes that enable them to fertilize the egg. During this process of
      capacitation, they acquire progressive motility, develop hyperactivated motility,
      and are readied for the acrosome reaction. All of these processes are regulated
      by intracellular pH. In the female reproductive tract, the spermatozoan cytoplasm
      alkalinizes, which in turn activates a Ca2+-selective current (I(CatSper))
      required for hyperactivated motility. Here, we show that alkalinization also has
      a dramatic effect on membrane potential, producing a rapid hyperpolarization.
      This hyperpolarization is primarily mediated by a weakly outwardly rectifying K+
      current (I(KSper)) originating from the principal piece of the sperm flagellum.
      Alkalinization activates the pH(i)-sensitive I(KSper), setting the membrane
      potential to negative potentials where Ca2+ entry via I(CatSper) is maximized.
      I(KSper) is one of two dominant ion currents of capacitated sperm cells.

PMID- 17460040
TI  - It's elementary: enhancing Fe3+ reduction improves rice yields.

PMID- 17460041
TI  - Perinatal exposure to a noncoplanar polychlorinated biphenyl alters tonotopy,
      receptive fields, and plasticity in rat primary auditory cortex.
AB  - Noncoplanar polychlorinated biphenyls (PCBs) are widely dispersed in human
      environment and tissues. Here, an exemplar noncoplanar PCB was fed to rat dams
      during gestation and throughout three subsequent nursing weeks. Although the
      hearing sensitivity and brainstem auditory responses of pups were normal,
      exposure resulted in the abnormal development of the primary auditory cortex
      (A1). A1 was irregularly shaped and marked by internal nonresponsive zones, its
      topographic organization was grossly abnormal or reversed in about half of the
      exposed pups, the balance of neuronal inhibition to excitation for A1 neurons was
      disturbed, and the critical period plasticity that underlies normal postnatal
      auditory system development was significantly altered. These findings demonstrate
      that developmental exposure to this class of environmental contaminant alters
      cortical development. It is proposed that exposure to noncoplanar PCBs may
      contribute to common developmental disorders, especially in populations with
      heritable imbalances in neurotransmitter systems that regulate the ratio of
      inhibition and excitation in the brain. We conclude that the health implications
      associated with exposure to noncoplanar PCBs in human populations merit a more
      careful examination.

PMID- 17460042
TI  - Sacred bounds on rational resolution of violent political conflict.
AB  - We report a series of experiments carried out with Palestinian and Israeli
      participants showing that violent opposition to compromise over issues considered
      sacred is (i) increased by offering material incentives to compromise but (ii)
      decreased when the adversary makes symbolic compromises over their own sacred
      values. These results demonstrate some of the unique properties of reasoning and
      decision-making over sacred values. We show that the use of material incentives
      to promote the peaceful resolution of political and cultural conflicts may
      backfire when adversaries treat contested issues as sacred values.

PMID- 17460043
TI  - Adult-onset pulmonary fibrosis caused by mutations in telomerase.
AB  - Idiopathic pulmonary fibrosis (IPF) is an adult-onset, lethal, scarring lung
      disease of unknown etiology. Some individuals with IPF have a familial disorder
      that segregates as a dominant trait with incomplete penetrance. Here we used
      linkage to map the disease gene in two families to chromosome 5. Sequencing a
      candidate gene within the interval, TERT, revealed a missense mutation and a
      frameshift mutation that cosegregated with pulmonary disease in the two families.
      TERT encodes telomerase reverse transcriptase, which together with the RNA
      component of telomerase (TERC), is required to maintain telomere integrity.
      Sequencing the probands of 44 additional unrelated families and 44 sporadic cases
      of interstitial lung disease revealed five other mutations in TERT. A
      heterozygous mutation in TERC also was found in one family. Heterozygous carriers
      of all of the mutations in TERT or TERC had shorter telomeres than age-matched
      family members without the mutations. Thus, mutations in TERT or TERC that result
      in telomere shortening over time confer a dramatic increase in susceptibility to
      adult-onset IPF.

PMID- 17460044
TI  - Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125.
AB  - Retinoic acid-inducible gene I (RIG-I) plays a pivotal role in the regulation of
      cytokine production induced by pathogens. The RIG-I also augments the production
      of IFN and other cytokines via an amplification circuit. Because the production
      of cytokines is closely controlled, up- and down-regulation of RIG-I signaling
      also needs strict regulation. The mechanism of this regulation, however, remains
      elusive. Here, we found that RIG-I undergoes proteasomal degradation after
      conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5,
      a family protein of RIG-I as well as IPS-1, which is also a downstream protein of
      RIG-I signaling that results in suppressing the functions of these proteins.
      Because RNF125 is enhanced by IFN, these functions constitute a negative
      regulatory loop circuit for IFN production.

PMID- 17460046
TI  - Depth-mediated reversal of the effects of climate change on long-term growth
      rates of exploited marine fish.
AB  - The oceanographic consequences of climate change are increasingly well
      documented, but the biological impacts of this change on marine species much less
      so, in large part because of few long-term data sets. Using otolith analysis, we
      reconstructed historical changes in annual growth rates for the juveniles of
      eight long-lived fish species in the southwest Pacific, from as early as 1861.
      Six of the eight species show significant changes in growth rates during the last
      century, with the pattern differing systematically with depth. Increasing
      temperatures near the ocean surface correlate with increasing growth rates by
      species found in depths <250 m, whereas growth rates of deep-water (>1,000 m)
      species have declined substantially during the last century, which correlates
      with evidence of long-term cooling at these depths. The observations suggest that
      global climate change has enhanced some elements of productivity of the shallow
      water stocks but also has reduced the productivity, and possibly the resilience,
      of the already slow-growing deep-water species.

PMID- 17460045
TI  - The tiny eukaryote Ostreococcus provides genomic insights into the paradox of
      plankton speciation.
AB  - The smallest known eukaryotes, at approximately 1-mum diameter, are Ostreococcus
      tauri and related species of marine phytoplankton. The genome of Ostreococcus
      lucimarinus has been completed and compared with that of O. tauri. This
      comparison reveals surprising differences across orthologous chromosomes in the
      two species from highly syntenic chromosomes in most cases to chromosomes with
      almost no similarity. Species divergence in these phytoplankton is occurring
      through multiple mechanisms acting differently on different chromosomes and
      likely including acquisition of new genes through horizontal gene transfer. We
      speculate that this latter process may be involved in altering the cell-surface
      characteristics of each species. In addition, the genome of O. lucimarinus
      provides insights into the unique metal metabolism of these organisms, which are
      predicted to have a large number of selenocysteine-containing proteins.
      Selenoenzymes are more catalytically active than similar enzymes lacking
      selenium, and thus the cell may require less of that protein. As reported here,
      selenoenzymes, novel fusion proteins, and loss of some major protein families
      including ones associated with chromatin are likely important adaptations for
      achieving a small cell size.

PMID- 17460047
TI  - An allosteric model of circadian KaiC phosphorylation.
AB  - In a recent series of ground-breaking experiments, Nakajima et al. [Nakajima M,
      Imai K, Ito H, Nishiwaki T, Murayama Y, Iwasaki H, Oyama T, Kondo T (2005)
      Science 308:414-415] showed that the three cyanobacterial clock proteins KaiA,
      KaiB, and KaiC are sufficient in vitro to generate circadian phosphorylation of
      KaiC. Here, we present a mathematical model of the Kai system. At its heart is
      the assumption that KaiC can exist in two conformational states, one favoring
      phosphorylation and the other dephosphorylation. Each individual KaiC hexamer
      then has a propensity to be phosphorylated in a cyclic manner. To generate
      macroscopic oscillations, however, the phosphorylation cycles of the different
      hexamers must be synchronized. We propose a novel synchronization mechanism based
      on differential affinity: KaiA stimulates KaiC phosphorylation, but the limited
      supply of KaiA dimers binds preferentially to those KaiC hexamers that are
      falling behind in the oscillation. KaiB sequesters KaiA and stabilizes the
      dephosphorylating KaiC state. We show that our model can reproduce a wide range
      of published data, including the observed insensitivity of the oscillation period
      to variations in temperature, and that it makes nontrivial predictions about the
      effects of varying the concentrations of the Kai proteins.

PMID- 17460048
TI  - Protein-induced, previously unidentified twin form of calcite.
AB  - Using single-crystal x-ray diffraction, we found a formerly unknown twin form in
      calcite crystals grown from solution to which a mollusc shell-derived 17-kDa
      protein, Caspartin, was added. This intracrystalline protein was extracted from
      the calcitic prisms of the Pinna nobilis shells. The observed twin form is
      characterized by the twinning plane of the (108)-type, which is in addition to
      the known four twin laws of calcite identified during 150 years of
      investigations. The established twin forms in calcite have twinning planes of the
      (001)-, (012)-, (104)-, and (018)-types. Our discovery provides additional
      evidence on the crucial role of biological macromolecules in biomineralization.

PMID- 17460050
TI  - Assessment of fluorescent in situ hybridization and PCR-based methods for rapid
      identification of Burkholderia cepacia complex organisms directly from sputum
      samples.
AB  - Several species within the Burkholderia cepacia complex (BCC) have emerged as
      significant opportunistic pathogens of patients with cystic fibrosis (CF). BCC
      infection is typically associated with a poor clinical prognosis and decreased
      survival. These factors, combined with the existence of highly transmissible
      epidemic strains, have resulted in strict segregation of BCC- and non-BCC
      infected patients to minimize cross infection. Accurate and rapid diagnosis of
      infections is essential to enable appropriate patient management. However, the
      rapidly evolving taxonomy of BCC poses a considerable challenge to diagnostics.
      In the present study, we assessed a commercially available fluorescent in situ
      hybridization (FISH) assay (seaFAST Cystic Fibrosis I kit) and a novel rRNA gene
      based PCR assay for the rapid identification of BCC-positive sputa, irrespective
      of the BCC species. We report that, while the FISH assay fails to identify all
      BCC species, it does identify the majority of species, including the two most
      clinically relevant species, B. multivorans and B. cenocepacia. The sensitivity
      of the assay applied to sputum was limited by nonspecific background
      fluorescence. While sputum processing was optimized to minimize background, the
      resulting sensitivity for BCC detection was 8 x 10(5) CFU/ml. In contrast, the
      novel PCR assay reported herein exhibits 100% sensitivity and specificity for all
      BCC species and can detect 10(4) CFU/ml when applied to sputum. This novel rRNA
      gene-based assay is currently the most sensitive BCC-specific PCR assay for the
      detection of BCC direct from clinical samples and as such is a valuable addition
      to the field of BCC diagnostics.

PMID- 17460049
TI  - Akt1 governs breast cancer progression in vivo.
AB  - The serine threonine kinase Akt1 has been implicated in the control of cellular
      metabolism, survival and growth. Here, disruption of the ubiquitously expressed
      member of the Akt family of genes, Akt1, in the mouse demonstrates a requirement
      for Akt1 in ErbB2-induced mammary tumorigenesis. Akt1 deficiency delayed tumor
      growth and reduced lung metastases, correlating with a reduction in
      phosphorylation of the Akt1 target, tuberous sclerosis 2 (TSC2) at Ser-939. Akt1
      deficient mammary epithelial tumor cells (MEC) were reduced in size and
      proliferative capacity, with reduced cyclin D1 and p27(KIP1) abundance. Akt1
      deficiency abrogated the oncogene-induced changes in polarization of MEC in three
      dimensional culture and reverted oncogene-induced relocalization of the
      phosphorylated ezrin-radixin-moesin proteins. Akt1 increased MEC migration across
      an endothelial cell barrier, enhancing the persistence of migratory
      directionality. An unbiased proteomic analysis demonstrated Akt1 mediated MEC
      migration through paracrine signaling via induction of expression and secretion
      of CXCL16 and MIP1gamma. Akt1 governs MEC polarity, migratory directionality and
      breast cancer onset induced by ErbB2 in vivo.

PMID- 17460051
TI  - A cluster of Legionella-associated pneumonia cases in a population of military
      recruits.
AB  - A Legionella cluster was identified through retrospective PCR analysis of 240
      throat swab samples from X-ray-confirmed pneumonia cases. These were identified
      among young and otherwise healthy U.S. military recruits during population-based
      surveillance for pneumonia pathogens. Results were confirmed by sequence
      analysis. Cases clustered tightly, suggesting a local environmental etiology.

PMID- 17460052
TI  - Biofilm production by Candida species and inadequate antifungal therapy as
      predictors of mortality for patients with candidemia.
AB  - Nosocomial Candida bloodstream infections rank among infections with highest
      mortality rates. A retrospective cohort analysis was conducted at Catholic
      University Hospital to estimate the risk factors for mortality of patients with
      candidemia. We reviewed records for patients with a Candida bloodstream infection
      over a 5-year period (January 2000 through December 2004). Two hundred ninety
      four patients (42.1% male; mean age +/- standard deviation, 65 +/- 12 years) were
      studied. Patients most commonly were admitted with a surgical diagnosis (162
      patients [55.1%]), had a central venous catheter (213 [72.4%]), cancer (118
      [40.1%]), or diabetes (58 [19.7%]). One hundred fifty-four (52.3%) patients died
      within 30 days. Of 294 patients, 168 (57.1%) were infected by Candida albicans,
      64 (21.7%) by Candida parapsilosis, 28 (9.5%) by Candida tropicalis, and 26
      (8.8%) by Candida glabrata. When fungal isolates were tested for biofilm
      formation capacity, biofilm production was most commonly observed for isolates of
      C. tropicalis (20 of 28 patients [71.4%]), followed by C. glabrata (6 of 26
      [23.1%]), C. albicans (38 of 168 [22.6%]), and C. parapsilosis (14 of 64
      [21.8%]). Multivariable analysis identified inadequate antifungal therapy (odds
      ratio [OR], 2.35; 95% confidence interval [95% CI], 1.09 to 5.10; P = 0.03),
      infection with overall biofilm-forming Candida species (OR, 2.33; 95% CI, 1.26 to
      4.30; P = 0.007), and Acute Physiology and Chronic Health Evaluation III scores
      (OR, 1.03; 95% CI, 1.01 to 1.15; P < 0.001) as independent predictors of
      mortality. Notably, if mortality was analyzed according to the different biofilm
      forming Candida species studied, only infections caused by C. albicans (P <
      0.001) and C. parapsilosis (P = 0.003) correlated with increased mortality.
      Together with well-established factors, Candida biofilm production was therefore
      shown to be associated with greater mortality of patients with candidemia,
      probably by preventing complete organism eradication from the blood.

PMID- 17460053
TI  - Discovery of a novel human picornavirus in a stool sample from a pediatric
      patient presenting with fever of unknown origin.
AB  - Fever of unknown origin (FUO) is a serious problem in the United States. An
      unidentified agent was cultured from the stool of an infant who presented with
      FUO. This virus showed growth in HFDK cells and suckling mice. Using DNase
      sequence-independent single-primer amplification, we identified several
      nucleotide sequences with a high homology to Theiler's murine encephalomyelitis
      virus. Nearly full-length viral genome sequencing and phylogenetic analysis
      demonstrate that this virus is a member of the Cardiovirus genus of the
      Picornaviridae family.

PMID- 17460054
TI  - Genetic and phenotypic features of blood and genital viral populations of
      clinically asymptomatic and antiretroviral-treatment-naive clade a human
      immunodeficiency virus type 1-infected women.
AB  - In the present study, we assessed whether human immunodeficiency virus type 1
      (HIV-1) genetic compartmentalization was associated with phenotypic CCR5 (R5) or
      CXCR4 (X4) coreceptor usage differences between the systemic and the genital
      viral populations. Four clinically asymptomatic and treatment-naive clade A HIV-1
      infected patients were selected from a cohort of 274 African women, because they
      were free of all the biological cofactors known to modify the kinetics of viral
      production in the genital tract. HIV RNA envelope sequences (V1 to V3) derived
      from plasma and cervicovaginal secretions (CVS) were amplified, subcloned, and
      sequenced. CCR5 or CXCR4 coreceptor usage was determined by production of
      recombinant viral particles, followed by single-cycle infection assays of
      indicator cell lines, using the tropism recombinant test. In these four selected
      patients, CVS-derived sequences appeared to be genetically distinct from blood
      derived sequences (P < or = 0.001). Two patients were found to harbor virus
      populations with only the R5 phenotype in both compartments, whereas viruses
      using CXCR4 in addition to CCR5 were detected in two other patients. In
      particular, one woman harbored genital virus populations with mixed R5 and X4
      phenotypes associated with peripheral blood populations with only the R5
      phenotype. These results demonstrate genetic compartmentalization of HIV between
      the plasma and genital secretions of clinically asymptomatic, treatment-naive,
      clade A-infected women. Also, for one patient, we report phenotypic coreceptor
      usage differences between the systemic (R5) and genital (R5/X4) viral
      populations. These features may be critical for the development of further
      mucosal vaccines, therapies, or new preventive strategies to block heterosexual
      transmission.

PMID- 17460055
TI  - Three-year longitudinal study of genotypes of Mycobacterium tuberculosis isolates
      in Tuscany, Italy.
AB  - The genetic diversity of 829 strains of Mycobacterium tuberculosis isolated
      during a 3-year period in Tuscany, Italy, a country with a low prevalence of
      tuberculosis, from 480 Italian-born and 349 foreign-born patients was determined
      by spoligotyping. The predominant spoligotype families were T (30.2% of
      isolates), Haarlem (19.9%), and the Latino-American and Mediterranean family
      (LAM) (11.2%); the remaining isolates were distributed among the Beijing (6.5%),
      S (4.2%), East Africa-India (EAI) (3.0%), Bovis (2.3%), Central Asia (CAS)
      (2.1%), Africanum (1.3%), and X (1.2%) families or were undefined (2.7%) or
      orphan (14.1%) isolates. Isolates of the families T, Haarlem, Bovis, and X were
      distributed among Italian- and foreign-born patients almost proportionally to the
      patients' numbers. Isolates of the LAM family were prevalent in foreign-born
      people (13.5%, versus 9.6% in Italian-born patients). Isolates of the S family
      were found almost exclusively in Italian-born patients, while strains of families
      EAI and CAS were isolated almost exclusively from foreign-born patients;
      Africanum isolates were all from African-born patients. The isolates of the
      Beijing family showed a trend to a steady increase during the survey. The
      prevalence of Beijing strains was 11.7% among foreign-born people and 2.7% among
      Italian-born patients. The Beijing strains were typed by the standardized IS6110
      restriction fragment length polymorphism assay, which yielded a total of 38
      distinct IS6110 patterns; 21 isolates (39.6%) occurred in six distinct clusters;
      of these, three contained two isolates and the other three contained four, five
      and six isolates, thus demonstrating that Beijing strains caused several
      tuberculosis outbreaks in the region. These findings indicate that transmission
      of Beijing strains between immigrants and the autochthonous population has
      occurred frequently and suggests an ongoing active transmission of the Beijing
      genotype in the region.

PMID- 17460056
TI  - Outbreak of human metapneumovirus detected by use of the Vero E6 cell line in
      isolates collected in Yamagata, Japan, in 2004 and 2005.
AB  - A number of epidemiological studies have shown human metapneumovirus (hMPV) to be
      one of the most important viral agents associated with acute respiratory
      infections in humans. However, due to the difficulty in growing the virus, all
      epidemiological studies of hMPV infection have been performed on the basis of the
      molecular method. Thus, the development of a cell line suitable for the isolation
      of hMPV from clinical specimens is a crucial step for further research. Using the
      Vero E6 cell line, which could be stably maintained for 1 month without passage
      or medium change, we succeeded in isolating 79 strains from 4,112 specimens
      obtained in Yamagata, Japan, in 2004 and 2005. The total isolation rate was 1.9%
      (79/4,112). The monthly distribution revealed that hMPV infections occurred
      between February and April in 2004 and throughout most of the year in 2005.
      Phylogenetic analysis indicated that subgenogroup B2 was predominant in 2004,
      whereas three subgenogroups, A2, B1, and B2, had cocirculated in 2005. Although
      multiple subgenogroups cocirculated in 2005, each individual subgenogroup strain
      was found to predominate at specific sites. An infectivity assay of hMPV strains
      also indicated that the infection efficiency in Vero E6 cells was better than
      that in LLC-MK2 cells. Finally, we found that Vero E6 cells are useful for the
      isolation of hMPVs and that this utility might aid further research into hMPVs
      beyond the epidemiological data shown in this study.

PMID- 17460057
TI  - Prevalence of anti-hepatitis E virus antibodies in French blood donors.
AB  - Accumulating evidence suggests that hepatitis E virus (HEV) infection is an
      emerging disease in regions where HEV is nonendemic. In France, the prevalence of
      anti-HEV antibodies in the general population has never been studied. Using blood
      donors' samples, we have found a prevalence of 3.20%, which is similar to that of
      other industrialized countries.

PMID- 17460058
TI  - Nonoutbreak surveillance of group A streptococci causing invasive disease in
      Portugal identified internationally disseminated clones among members of a
      genetically heterogeneous population.
AB  - The typing of 160 invasive Streptococcus pyogenes isolates confirmed the
      importance of pulsed-field gel electrophoresis and multilocus sequence typing for
      defining clones. The results identified an extremely diverse population and
      highlighted the importance of both internationally disseminated and local clones
      not previously associated with invasive disease.

PMID- 17460059
TI  - Nucleotide sequence diversity of the bexA gene in serotypeable Haemophilus
      influenzae strains recovered from invasive disease patients in Canada.
AB  - The bexA genes of 36 Haemophilus influenzae isolates were sequenced to reveal
      their nucleotide sequence diversity, which divided them into two groups, similar
      to clonal divisions I and II. This sequence diversity may lead to false-negative
      PCR results for H. influenzae infections if bexA is the chosen gene target.

PMID- 17460060
TI  - Targeted and untargeted CD137L fusion proteins for the immunotherapy of
      experimental solid tumors.
AB  - INTRODUCTION: CD137L is a member of the tumor necrosis factor superfamily that
      provides a costimulatory signal to T cells. In this study, two novel CD137L
      fusion proteins were produced and compared with the CD137 agonist antibody 2A.
      MATERIALS AND METHODS: Murine CD137L was linked to the COOH terminus of either
      the Fc fragment of immunoglobulin (untargeted version) or TNT-3 (targeted
      version), an antibody that binds to necrotic regions of tumors. Groups of mice
      bearing established Colon 26 tumors were then treated daily x 5 with each fusion
      protein or 2A to determine their immunotherapeutic potential. RESULTS: Both
      fusion proteins retained CD137L activity in vitro and TNT-3/CD137L showed tumor
      binding activity by biodistribution analysis in tumor-bearing mice. The fusion
      proteins also produced similar responses in vivo at the 1 nmol per dose range and
      showed a 60% (TNT-3/CD137L) or 40% (Fc/CD137L) survival of treated mice at 150
      days after tumor implantation, similar to the effects of 2A. Morphologic and
      immunohistochemical analyses showed massive central necrosis and infiltration of
      granzyme B-positive cells in necrotic areas and viable peripheral regions of
      treated tumors. Finally, cell depletion studies showed that CD137L-mediated tumor
      regression was CD8(+) T cell dependent. CONCLUSIONS: From these studies, it was
      determined that both targeted and untargeted CD137L fusion proteins showed
      effective antitumor activity, but that the targeted version was more potent.
      Therefore, the use of the natural CD137 ligand is a promising approach to the
      treatment of solid tumors by virtue of its ability to produce physiologic
      costimulation within the tumor, limiting side effects often seen with agonist
      antibody therapies.

PMID- 17460061
TI  - On the move from academia to industry: established neuroscientists who have made
      the transition from academia to industry are finding different rewards in a new
      environment.

PMID- 17460062
TI  - Acquiring visual object expertise: reorganization in the ventral path.

PMID- 17460063
TI  - CNS progenitor cells promote a permissive environment for neurite outgrowth via a
      matrix metalloproteinase-2-dependent mechanism.
AB  - Transplantation of progenitor cells to the CNS has shown promise in neuronal and
      glial replacement and as a means of rescuing host neurons from apoptosis. Here we
      examined the effect of progenitor grafts on neurite extension in the degenerating
      retina of rd1 (retinal degeneration 1) mice. Transplantation of retinal
      progenitor cells induced increased matrix metalloproteinase-2 (MMP2) secretion,
      partly from activated glial cells, which was then activated by neuronally
      expressed MMP14. Active MMP2 resulted in proteolysis of the neurite outgrowth
      inhibitors CD44 and neurocan in the degenerative retina, allowing significantly
      increased neurite outgrowth across the border between abutting nondystrophic and
      rd1 retinas. Progenitor-induced enhancement of outgrowth was abrogated by an MMP
      inhibitor or by coculture with retinal explants from MMP2-/- mice. This study
      provides the first identification of an MMP2-dependent mechanism by which
      exogenous progenitor cells alter the host environment to promote neural
      regeneration. This suggests a novel therapeutic role for progenitor cells in the
      treatment of CNS degenerative diseases.

PMID- 17460064
TI  - Persistent sodium currents participate in fictive locomotion generation in
      neonatal mouse spinal cord.
AB  - The persistent sodium current (I(Na(P))) has been implicated in the regulation of
      synaptic integration, intrinsic membrane properties, and rhythm generation in
      many types of neurons. We characterized I(Na(P)) in commissural interneurons
      (CINs) in the neonatal (postnatal days 0-3) mouse spinal cord; it is activated at
      subthreshold potentials, inactivates slowly, and can be blocked by low
      concentrations of riluzole. The role of I(Na(P)) in locomotor pattern generation
      was examined by applying riluzole during fictive locomotion induced by NMDA,
      serotonin, and dopamine or by stimulation of the cauda equina. Blockade of
      I(Na(P)) has marginal effects on the locomotion frequency but progressively
      weakens the rhythmic firing and locomotor-related membrane oscillation of CINs
      and motoneurons (MNs) and the locomotor-like bursts in ventral roots, until the
      motor pattern ceases. Riluzole directly affects the intrinsic firing properties
      of CINs and MNs, reducing their ability to fire repetitively during tonic
      depolarizations and raising their spike threshold. At the same time, riluzole has
      little effects on the strength of spike-evoked synaptic transmission onto CINs
      and MNs. Our results suggest that I(Na(P)) is essential for the generation of the
      locomotor pattern and acts in part by regulating the frequency of interneuron
      firing in the central pattern generator for locomotion.

PMID- 17460065
TI  - Neuregulin1 (NRG1) signaling through Fyn modulates NMDA receptor phosphorylation:
      differential synaptic function in NRG1+/- knock-outs compared with wild-type
      mice.
AB  - We previously identified Neuregulin1 (NRG1) as a gene contributing to the risk of
      developing schizophrenia. Furthermore, we showed that NRG1+/- mutant mice display
      behavioral abnormalities that are reversed by clozapine, an atypical
      antipsychotic drug used for the treatment of schizophrenia. We now present
      evidence that ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4),
      the tyrosine kinase receptor for NRG1 in hippocampal neurons, interacts with two
      nonreceptor tyrosine kinases, Fyn and Pyk2 (proline-rich tyrosine kinase 2). NRG1
      stimulation of cells expressing ErbB4 and Fyn leads to the association of Fyn
      with ErbB4 and consequent activation. Furthermore, we show that NRG1 signaling,
      through activation of Fyn and Pyk2 kinases, stimulates phosphorylation of Y1472
      on the NR2B subunit of the NMDA receptor (NMDAR), a key regulatory site that
      modulates channel properties. NR2B Y1472 is hypophosphorylated in NRG1+/- mutant
      mice, and this defect can be reversed by clozapine at a dose that reverses their
      behavioral abnormalities. We also demonstrate that short-term synaptic plasticity
      is altered and theta-burst long-term potentiation is impaired in NRG1+/- mutant
      mice, and incubation of hippocampal slices from these mice with NRG1 reversed
      those effects. Attenuated NRG1 signaling through ErbB4 may contribute to the
      pathophysiology of schizophrenia through dysfunction of NMDAR modulation. Thus,
      our data support the glutamate hypothesis of schizophrenia.

PMID- 17460066
TI  - Transient synaptic silencing of developing striate cortex has persistent effects
      on visual function and plasticity.
AB  - Neural circuits in the cerebral cortex are shaped by experience during "critical
      periods" early in life. For example, visual cortex is immature at the time of eye
      opening and gradually develops its functional properties during a sensitive
      period. Very few reports have addressed the role of intrinsic neural activity in
      cortical maturation. Here we have exploited the bacterial enzyme botulinum
      neurotoxin E (BoNT/E) to produce a unilateral, reversible blockade of neural
      activity in rat visual cortex during the sensitive period. BoNT/E is a highly
      selective protease that interferes with transmitter release via cleavage of the
      synaptic protein SNAP-25 (synaptosomal-associated protein of 25 kDa). Unilateral,
      intracortical injections of BoNT/E were made at the time of eye opening and
      resulted in the silencing of the treated, but not contralateral, hemisphere for a
      period of 2 weeks. We found that visual acuity was permanently reduced in the
      blocked hemisphere, and the critical period for ocular dominance plasticity
      persisted into adulthood. Unexpectedly, these effects extended equally to the
      contralateral, uninjected side, demonstrating a fundamental role for
      interhemispheric connections in cortical maturation.

PMID- 17460067
TI  - Drosophila homer is required in a small set of neurons including the ellipsoid
      body for normal ethanol sensitivity and tolerance.
AB  - The molecular mechanisms occurring in the nervous system that underlie behavioral
      responses to ethanol remain poorly understood. Here, we report that molecular
      requirements for two of these responses, initial sensitivity and the development
      of rapid tolerance, comap to the same small set of neurons. We show that null
      homer mutant flies exhibit both increased sensitivity to the sedative effects of
      ethanol and failure to develop normal levels of rapid tolerance. Both the
      sensitivity and rapid tolerance phenotypes of the homer mutants are rescued by
      the expression of wild-type homer in a subset of neurons that include the
      ellipsoid body. Thus, some of the molecular- and systems-level requirements for
      these two behavioral responses to ethanol are identical.

PMID- 17460068
TI  - Upregulation of polysialylated neural cell adhesion molecule in the dorsal
      hippocampus after contextual fear conditioning is involved in long-term memory
      formation.
AB  - The role of the hippocampus in pavlovian fear conditioning is controversial.
      Although lesion and pharmacological inactivation studies have suggested a key
      role for the dorsal hippocampus in contextual fear conditioning, the involvement
      of the ventral part is still uncertain. Likewise, the debate is open with regard
      to the putative implication of each hippocampal subdivision in fear conditioning
      to a discrete conditioned stimulus. We explored the potential existence of
      dissociations occurring in the dorsal versus ventral hippocampus at the cellular
      level while dealing with either contextual or cued fear conditioning and focused
      in a molecular "signature" linked to structural plasticity, the polysialylated
      form of the neural cell adhesion molecule (PSA-NCAM). We found an upregulation of
      PSA-NCAM expression in the dorsal (but not ventral) dentate gyrus at 24 h after
      contextual (but not tone) fear conditioning. Specific removal of PSA through
      microinfusion of the enzyme endoneuraminidase-N in the dorsal (but not ventral)
      hippocampus reduced freezing responses to the conditioned context. Therefore, we
      present evidence for a specific role of PSA-NCAM in the dorsal hippocampus in the
      plasticity processes occurring during consolidation of the context representation
      after "standard" contextual fear conditioning. Interestingly, we also found that
      exposing animals just to the context induced an activation of PSA-NCAM in both
      dorsal and ventral dentate gyrus. Altogether, these findings highlighting the
      distinctive occurrence of these neuroplastic processes in the dorsal hippocampus
      during the standard contextual fear-conditioning task enlighten the ongoing
      debate about the involvement of these hippocampal subdivisions in pavlovian fear
      conditioning.

PMID- 17460069
TI  - Phosphatidylinositol 3-Akt-kinase-dependent phosphorylation of p21(Waf1/Cip1) as
      a novel mechanism of neuroprotection by glucocorticoids.
AB  - The role of glucocorticoids in the regulation of apoptosis remains incongruous.
      Here, we demonstrate that corticosterone protects neurons from apoptosis by a
      mechanism involving the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). In
      primary cortical neurons, corticosterone leads to a dose- and Akt-kinase
      dependent upregulation with enhanced phosphorylation and cytoplasmic appearance
      of p21(Waf1/Cip1) at Thr 145. Exposure of neurons to the neurotoxin ethylcholine
      aziridinium (AF64A) results in activation of caspase-3 and a dramatic loss of
      p21(Waf1/Cip1) preceding apoptosis in neurons. These effects of AF64A are
      reversed by pretreatment with corticosterone. Corticosterone-mediated
      upregulation of p21(Waf1/Cip1) and neuroprotection are completely abolished by
      glucocorticoid and mineralocorticoid receptor antagonists as well as inhibitors
      of PI3- and Akt-kinase. Both germline and somatically induced p21(Waf1/Cip1)
      deficiency abrogate the neuroprotection by corticosterone, whereas overexpression
      of p21(Waf1/Cip1) suffices to protect neurons from apoptosis. We identify
      p21(Waf1/Cip1) as a novel antiapoptotic factor for postmitotic neurons and
      implicate p21(Waf1/Cip1) as the molecular target of neuroprotection by high-dose
      glucocorticoids.

PMID- 17460070
TI  - The triphasic intrinsic signal: implications for functional imaging.
AB  - Intrinsic signal optical imaging with red illumination (ISOI) is used extensively
      to provide high spatial resolution maps of stimulus-evoked hemodynamic-related
      signals as an indirect means to map evoked neuronal activity. This evoked signal
      is generally described as beginning with an undershoot or "dip" in signal that is
      faster, more transient, and weaker compared with the subsequent signal overshoot.
      In contrast, the evoked signal detected with blood oxygen level-dependent (BOLD)
      functional magnetic resonance imaging (fMRI) is generally described as containing
      an undershoot after the initial dip and overshoot, even though it, too, detects
      hemodynamic-related signals and its first two phases appear complementary to
      those of ISOI. Here, we used ISOI with 635 nm illumination to image over 13.5 s
      after a 1 s stimulus delivery to detect and successfully use the ISOI undershoot
      phase for functional mapping. Eight spatiotemporal attributes were assessed per
      signal phase including maximum areal extent and peak magnitude, both of which
      were largest for the ISOI overshoot, followed by the undershoot and then the
      initial dip. Peak activity location did not colocalize well between the three
      phases; furthermore, we found mostly modest correlations between attributes
      within each phase and sparse correlations between phases. Extended (13.5 s)
      electrophysiology recordings did not exhibit a reoccurrence of evoked
      suprathreshold or subthreshold neuronal responses that could be associated with
      the undershoot. Beyond the undershoot, additional overshoot/undershoot
      fluctuations were also mapped, but were typically less spatiotemporally specific
      to stimulus delivery. Implications for ISOI and BOLD fMRI are discussed.

PMID- 17460071
TI  - Functional dissociation in frontal and striatal areas for processing of positive
      and negative reward information.
AB  - Reward-seeking behavior depends critically on processing of positive and negative
      information at various stages such as reward anticipation, outcome monitoring,
      and choice evaluation. Behavioral and neuropsychological evidence suggests that
      processing of positive (e.g., gain) and negative (e.g., loss) reward information
      may be dissociable and individually disrupted. However, it remains uncertain
      whether different stages of reward processing share certain neural circuitry in
      frontal and striatal areas, and whether distinct but interactive systems in these
      areas are recruited for positive and negative reward processing. To explore these
      issues, we used a monetary decision-making task to investigate the roles of
      frontal and striatal areas at all three stages of reward processing in the same
      event-related functional magnetic resonance imaging experiment. Participants were
      instructed to choose whether to bet or bank a certain number of chips. If they
      decided to bank or if they lost a bet, they started over betting one chip. If
      they won a bet, the wager was doubled in the next round. Positive reward
      anticipation, winning outcome, and evaluation of right choices activated the
      striatum and medial/middle orbitofrontal cortex, whereas negative reward
      anticipation, losing outcome, and evaluation of wrong choices activated the
      lateral orbitofrontal cortex, anterior insula, superior temporal pole, and
      dorsomedial frontal cortex. These findings suggest that the valence of reward
      information and counterfactual comparison more strongly predict a functional
      dissociation in frontal and striatal areas than do various stages of reward
      processing. These distinct but interactive systems may serve to guide human's
      reward-seeking behavior.

PMID- 17460072
TI  - Conservation of glutamate receptor 2-containing AMPA receptors during long-term
      potentiation.
AB  - Long-term potentiation (LTP) at hippocampal synapses is thought to involve the
      insertion of AMPA receptors into the postsynaptic membrane. Conflicting evidence
      exists as to whether calcium-permeable receptors are inserted during LTP and
      whether synaptic activity mediated by the newly inserted AMPA receptors is
      required to maintain the increase in synaptic strength. Here, we rigorously test
      these hypotheses and conclude that calcium-permeable AMPA receptors are not
      inserted during LTP nor does potentiation require ongoing activity to be
      maintained.

PMID- 17460073
TI  - Activity-dependent presynaptic and postsynaptic structural plasticity in the
      mature cerebellum.
AB  - Two models of spine formation have been proposed. Spines can derive from emerging
      dendritic filopodia that have encountered presynaptic partners, or presynaptic
      molecules may induce the spine maturation event directly from the dendritic
      shaft. The first model applies better to the Purkinje cell (PC), because numerous
      free spines have been described in several conditions, particularly when granule
      cells degenerate before parallel fiber (PF) synapses are formed. A large number
      of new spines, many of them being free, appear in the proximal dendritic domain
      after blockage of electrical activity by tetrodotoxin (TTX). A complete blockage
      of the AMPA receptors by NBQX (2,3-dioxo-6-nitro-1,2,3,4
      tetrahydrobenzoquinoxaline-7-sulfonamide), leading to a complete absence of PF-
      and climbing fiber (CF)-evoked EPSCs and of spontaneous glutamatergic quantal
      events, mimics the TTX effect. In contrast, metabotropic glutamate receptor
      blockage by MCPG [(S)-alpha-methyl-4-carboxyphenylglycine] is ineffective. In
      normal conditions, in the proximal dendritic domain of the PC, clusters of a few
      spines are present only under each CF varicosity. It has been proposed that the
      active CF is responsible for spine pruning in the territory surrounding the CF
      synapses. Here, we show that such a pruning is mediated by AMPA but not by
      metabotropic receptors. Finally, after AMPA receptor blockage, there is a reduced
      number of spines in each spine cluster underlying CF varicosity. In conclusion,
      PCs tend to express spines over the entire dendritic territory. CF activity
      reinforces the CF synaptic contacts and actively suppresses spines in the
      surrounding territory, which is an effect mediated by AMPA receptors.

PMID- 17460074
TI  - Memory traces of pain in human cortex.
AB  - Distinct brain regions process sensory discriminative and affective components of
      pain; however, the role of these areas in pain memory is unknown. This event
      related study investigated the short-term memory for sensory features of
      cutaneous heat pain using a delayed-discrimination paradigm and functional
      magnetic resonance imaging. During memory trials, subjects discriminated the
      location and intensity of two painful stimuli presented sequentially to the right
      hand. Control trials comprised the same sequence of stimuli and motor responses
      but required no delayed discrimination. Stimulus-evoked activity for memory and
      control trials was generally indistinguishable within the network of regions
      normally responsive to experimental pain [i.e., the primary somatosensory
      cortex/posterior parietal cortex (SI/PPC), secondary somatosensory cortex (SII),
      and anterior insular cortex (aIC)]; these data confirm the painful nature of the
      stimuli and the similar levels of attention and stimulus encoding engaged during
      the two randomly presented trial types. Memory-specific activity, assessed by
      contrasting the interstimulus interval in memory and control trials, was observed
      in SI/PPC and aIC but not in SII. We propose that SI/PPC plays a role in the
      short-term retention of spatial and intensity aspects of noxious stimuli and that
      aIC activation during memory trials is consistent with the integration of sensory
      and cognitive (attention, awareness, salience, and memory) components of pain
      perception. The absence of memory-specific anterior cingulate cortex activation,
      generally associated with pain unpleasantness, suggests that remembering
      affective aspects of the stimuli was not required during performance of the
      sensory delayed-discrimination task.

PMID- 17460075
TI  - Compensatory plasticity at an identified synapse tunes a visuomotor pathway.
AB  - We characterized homeostatic plasticity at an identified sensory-motor synapse in
      an insect, which maintains constant levels of motor drive as locusts transform
      from their solitarious phase to their gregarious swarming phase. The same
      mechanism produces behaviorally relevant changes in response timing that can be
      understood in the context of an animal's altered behavioral state. For individual
      animals of either phase, different looming objects elicited different spiking
      responses in a visual looming detector interneuron, descending contralateral
      movement detector (DCMD), yet its synaptic drive to a leg motoneuron, fast
      extensor tibiae (FETi), always had the same maximum amplitude. Gregarious locust
      DCMDs produced more action potentials and had higher firing frequencies, but
      individual postsynaptic potentials (PSPs) elicited in FETi were half the
      amplitude of those in solitarious locusts. A model suggested that this alone
      could not explain the similarity in overall amplitude, and we show that
      facilitation increased the maximum compound PSP amplitude in gregarious animals.
      There was the same linear relationship between times of peak DCMD firing before
      collision and the size/velocity of looming objects in both phases. The DCMD-FETi
      synapse transformed this relationship nonlinearly, such that peak amplitudes of
      compound PSPs occurred disproportionately earlier for smaller/faster objects.
      Furthermore, the peak PSP amplitude occurred earlier in gregarious than in
      solitarious locusts, indicating a differential tuning. Homeostatic modulation of
      the amplitude, together with a nonlinear synaptic transformation of timing, acted
      together to tune the DCMD-FETi system so that swarming gregarious locusts respond
      earlier to small moving objects, such as conspecifics, than solitarious locusts.

PMID- 17460076
TI  - Spinal interneurons that are selectively activated during fictive flexion reflex.
AB  - Behavioral choices in invertebrates are mediated by a combination of shared and
      specialized circuitry, including neurons that are inhibited during competing
      behaviors. Less is known, however, about the neural mechanisms of behavioral
      choice in vertebrates. The spinal cord can appropriately select among several
      types of limb movements, including limb withdrawal (flexion reflex), scratching,
      and locomotion, and thus is conducive to examination of vertebrate mechanisms of
      behavioral choice. Flexion reflex can interrupt and reset the rhythm of
      scratching and locomotion, suggesting that a combination of shared and
      specialized circuitry contributes to these behaviors, but little is known about
      the interneurons involved. Here, I used in vivo intracellular recording and dye
      injection to identify a group of spinal interneurons that are strongly activated
      during fictive flexion reflex but inhibited during fictive scratching and fictive
      swimming. These flexion-selective interneurons are typically rhythmically
      hyperpolarized during fictive scratching and fictive swimming. This
      hyperpolarization can be maximal during the ipsilateral hip flexor bursts of
      rhythmic limb motor patterns, although these cells are strongly activated during
      the ipsilateral hip flexor bursts of fictive flexion reflex. Thus, these
      interneurons are relatively specialized for fictive limb withdrawal, rather than
      contributing to the hip flexor phase of multiple types of limb movements. These
      flexion-selective cells are physiologically and morphologically distinguishable
      from a recently described group of spinal interneurons (transverse interneurons)
      that are strongly activated during both fictive flexion reflex and fictive
      scratching. Thus, spinal interneurons with distinct behavioral roles may to some
      extent be morphologically distinguishable.

PMID- 17460077
TI  - Polymorphisms in the human soluble epoxide hydrolase gene EPHX2 linked to
      neuronal survival after ischemic injury.
AB  - Single nucleotide polymorphisms (SNPs) in the human EPHX2 gene have recently been
      implicated in susceptibility to cardiovascular disease, including stroke. EPHX2
      encodes for soluble epoxide hydrolase (sEH), an important enzyme in the metabolic
      breakdown of arachidonic acid-derived eicosanoids referred to as
      epoxyeicosatrienoic acids (EETs). We previously demonstrated that EETs are
      protective against ischemic cell death in culture. Therefore, we tested the
      hypothesis that polymorphisms in the human EPHX2 gene alter sEH enzyme activity
      and affect neuronal survival after ischemic injury in vitro. Human EPHX2 mutants
      were recreated by site-directed mutagenesis and fused downstream of TAT protein
      transduction domain. Western blot analysis and immunocytochemistry staining
      revealed high-transduction efficiency of human TAT-sEH variants in rat primary
      cultured cortical neurons, associated with increased metabolism of 14,15-EET to
      corresponding 14,15-dihydroxyeicosatrienoic acid. A human variant of sEH with
      Arg103Cys amino acid substitution, previously demonstrated to increase sEH
      enzymatic activity, was associated with increased cell death induced in cortical
      neurons by oxygen-glucose deprivation (OGD) and reoxygenation. In contrast, the
      Arg287Gln mutation was associated with reduced sEH activity and protection from
      OGD-induced neuronal cell death. We conclude that sequence variations in the
      human EPHX2 gene alter susceptibility to ischemic injury and neuronal survival in
      a manner linked to changes in the hydrolase activity of the enzyme. The findings
      suggest that human EPHX2 mutations may in part explain the genetic variability in
      sensitivity to ischemic brain injury and stroke outcome.

PMID- 17460078
TI  - Extensive reorganization of primary afferent projections into the gustatory
      brainstem induced by feeding a sodium-restricted diet during development: less is
      more.
AB  - Neural development is especially vulnerable to environmental influences during
      periods of neurogenesis and rapid maturation. In fact, short periods of
      environmental manipulations confined to embryonic development lead to significant
      changes in morphology and function. A guiding principal emerging from studies of
      sensory systems is that experimentally induced effects are most dramatic in
      higher neural levels (e.g., cortex) and primarily involve postnatal synaptic
      refinements. In contrast to other sensory systems, the gustatory system is
      particularly susceptible to the effects of deprivation much earlier and with
      profound changes evident in the brainstem. Here we show that feeding pregnant
      rats a custom diet featuring a low-sodium content for 9 d before the tongue
      appears in the fetus produces extensive restructuring of the gustatory brainstem.
      Rats born to mothers fed the custom diet from embryonic day 3 (E3) to E12 have
      terminal field volumes of the greater superficial petrosal, chorda tympani, and
      glossopharyngeal nerves at adulthood that are expanded as much as 10 times beyond
      that found in rats fed a standard rat chow. The widespread alterations are not
      attributable to increased numbers of nerve cells, increased target size, or
      obvious changes in peripheral taste function. Moreover, we show that the limited
      period of feeding the custom diet has much larger effects than if rats were fed
      the diet to postweaning ages. Our results suggest that early periods of altered
      experience, especially during nucleus of the solitary tract neurogenesis, leads
      to a restructuring of the gustatory brainstem, which in turn may impact the
      control of sensory and homeostatic processes.

PMID- 17460079
TI  - Adaptive depression in synaptic transmission in the nucleus of the solitary tract
      after in vivo chronic intermittent hypoxia: evidence for homeostatic plasticity.
AB  - The respiratory system is highly pliable in its adaptation to low-oxygen
      (hypoxic) environments. After chronic intermittent hypoxia (CIH), alterations in
      the regulation of cardiorespiratory system become persistent because of changes
      in the peripheral chemoreceptor reflex. We present evidence for the induction of
      a novel form of homeostatic plasticity in this reflex pathway in the nucleus
      tractus solitarius (NTS), the site of termination of the chemosensory afferent
      fibers. CIH induces an increase in NTS postsynaptic cell activity initiated by
      spontaneous presynaptic transmitter release that is counterbalanced by a
      reduction in evoked synaptic transmission between sensory afferents and NTS
      second-order cells. This is accomplished via presynaptic mechanisms involving
      changes in neurotransmitter release and calcium/calmodulin-dependent kinase II
      activation.

PMID- 17460080
TI  - Differential regulation of AMPA receptor trafficking by neurabin-targeted
      synaptic protein phosphatase-1 in synaptic transmission and long-term depression
      in hippocampus.
AB  - Filamentous actin binding protein neurabin I (NrbI) targets protein phosphatase-1
      (PP1) to specific postsynaptic microdomains, exerting critical control over AMPA
      receptor (AMPAR)-mediated synaptic transmission. NrbI-targeted synaptic PP1,
      which promotes synaptic depression upon long-term depression (LTD) stimuli,
      serves to prevent synaptic depression under basal conditions. The present studies
      investigate this opposite regulation of AMPAR trafficking during basal synaptic
      transmission and LTD by expressing NrbI or NrbI mutant, which is defective in PP1
      binding, in hippocampal slice or neuron cultures. We find that expression of the
      NrbI mutant to interfere with PP1 targeting dramatically reduces basal synaptic
      transmission, which is correlated with the reduction in surface expression of
      AMPA subtype glutamate receptor (GluR) 1 and GluR2 subunits. Biochemical analysis
      demonstrates that the NrbI mutant selectively increases the phosphorylation of
      GluR2 at C-terminal consensus PKC site, serine 880, which is known to favor GluR2
      interaction with PDZ (postsynaptic density 95/Discs large/zona occludens 1)
      protein PICK1 (protein interacting with C kinase-1). Inhibition of PKC activity
      or GluR2-PICK1 interaction completely reverses the synaptic depression in neurons
      expressing the NrbI mutant, suggesting that NrbI-targeted synaptic PP1 stabilizes
      the basal transmission by negatively controlling PKC phosphorylation of GluR2 and
      the subsequent PICK1-mediated decrease in GluR2-containing AMPAR surface
      expression. Distinct from basal transmission, blocking GluR2-PICK1 interaction or
      PKC activity produces minimal effects on LTD in NrbI-expressing neurons. Instead,
      NrbI-targeted PP1 facilitates LTD by dephosphorylating GluR1 at both serine 845
      and serine 831, with GluR2 serine 880 phosphorylation unaltered. Our studies thus
      elucidate that NrbI-targeted PP1, in response to distinct synaptic activities,
      regulates the synaptic trafficking of specific AMPAR subunits.

PMID- 17460081
TI  - Specificity of human cortical areas for reaches and saccades.
AB  - Electrophysiological studies in monkeys have identified effector-related regions
      in the posterior parietal cortex (PPC). The lateral intraparietal area, for
      example, responds preferentially for saccades, whereas the parietal reach region
      responds preferentially for arm movements. However, the degree of effector
      selectivity actually observed is limited; each area contains neurons selective
      for the nonpreferred effector, and many neurons in both areas respond for both
      effectors. We used functional magnetic resonance imaging to assess the degree of
      effector preference at the population level, focusing on topographically
      organized regions in the human PPC [visual area V7, intraparietal sulcus 1
      (IPS1), and IPS2]. An event-related design adapted from monkey experiments was
      used. In each trial, an effector cue preceded the appearance of a spatial target,
      after which a Go signal instructed subjects to produce the specified movement
      with the specified effector. Our results show that the degree of effector
      specificity is limited in many cortical areas and transitions gradually from
      saccade to reach preference as one moves through the hierarchy of areas in the
      occipital, parietal, and frontal cortices. Saccade preference was observed in
      visual cortex, including early areas and V7. IPS1 exhibited balanced activation
      to saccades and reaches, whereas IPS2 showed a weak but significant preference
      for reaches. In frontal cortex, areas near the central sulcus showed a clear and
      absolute preference for reaches, whereas the frontal eye field showed little or
      no effector selectivity. Although these results contradict many theoretical
      conclusions about effector specificity, they are compatible with the complex
      picture arising from electrophysiological studies and also with previous imaging
      studies that reported mostly overlapping saccade- and arm-related activation. The
      results are also compatible with theories of efficient coding in cortex.

PMID- 17460082
TI  - Localization of HCN1 channels to presynaptic compartments: novel plasticity that
      may contribute to hippocampal maturation.
AB  - Increasing evidence supports roles for the current mediated by hyperpolarization
      activated cyclic nucleotide-gated (HCN) channels, I(h), in hippocampal maturation
      and specifically in the evolving changes of intrinsic properties as well as
      network responses of hippocampal neurons. Here, we describe a novel developmental
      plasticity of HCN channel expression in axonal and presynaptic compartments: HCN1
      channels were localized to axon terminals of the perforant path (the major
      hippocampal afferent pathway) of immature rats, where they modulated synaptic
      efficacy. However, presynaptic expression and functions of the channels
      disappeared with maturation. This was a result of altered channel transport to
      the axons, because HCN1 mRNA and protein levels in entorhinal cortex neurons,
      where the perforant path axons originate, were stable through adulthood. Blocking
      action potential firing in vitro increased presynaptic expression of HCN1
      channels in the perforant path, suggesting that network activity contributed to
      regulating this expression. These findings support a novel developmentally
      regulated axonal transport of functional ion channels and suggest a role for HCN1
      channel-mediated presynaptic I(h) in hippocampal maturation.

PMID- 17460083
TI  - BK channels with beta3a subunits generate use-dependent slow afterhyperpolarizing
      currents by an inactivation-coupled mechanism.
AB  - Large-conductance, Ca2+- and voltage-activated K+ (BK) channels are broadly
      expressed proteins that respond to both cellular depolarization and elevations in
      cytosolic Ca2+. The characteristic functional properties of BK channels among
      different cells are determined, in part, by tissue-specific expression of
      auxiliary beta subunits. One important functional property conferred on BK
      channels by beta subunits is inactivation. Yet, the physiological role of BK
      channel inactivation remains poorly understood. Here we report that as a
      consequence of a specific mechanism of inactivation, BK channels containing the
      beta3a auxiliary subunit exhibit an anomalous slowing of channel closing. This
      produces a net repolarizing current flux that markedly exceeds that expected if
      all open channels had simply closed. Because of the time dependence of
      inactivation, this behavior results in a Ca2+-independent but time-dependent
      increase in a slow tail current, providing an unexpected mechanism by which use
      dependent changes in slow afterhyperpolarizations might regulate electrical
      firing. The physiological significance of inactivation in BK channels mediated by
      different beta subunits may therefore arise not from inactivation itself, but
      from the differences in the amplitude and duration of repolarizing currents
      arising from the beta-subunit-specific energetics of recovery from inactivation.

PMID- 17460084
TI  - IQGAP1 regulates adult neural progenitors in vivo and vascular endothelial growth
      factor-triggered neural progenitor migration in vitro.
AB  - In the germinative zone of the adult rodent brain, neural progenitors migrate
      into niches delimited by astrocyte processes and differentiate into neuronal
      precursors. In the present study, we report a modulating role for the scaffolding
      protein IQGAP1 in neural progenitor migration. We have identified IQGAP1 as a new
      marker of amplifying neural progenitor and neuronal precursor cells of the
      subventricular zone (SVZ) and the rostral migratory stream (RMS) in the adult
      mouse brain. To determine functions for IQGAP1 in neural progenitors, we compared
      the properties of neural progenitor cells from wild-type and Iqgap1-null mutant
      mice in vivo and in vitro. The in vivo studies reveal a delay in the transition
      of de novo neural progenitors into neuronal precursor cells in Iqgap1-null mice.
      In vitro, we demonstrated that IQGAP1 acts as a downstream effector in the
      vascular endothelial growth factor (VEGF)-dependent migratory response of neural
      progenitors that also impacts on their neuronal differentiation. The Rho-family
      GTPases cdc42/Rac1 and Lis1 are major partners of IQGAP1 in this migratory
      process. Finally, astrocytes of the neurogenic SVZ and RMS are shown to express
      VEGF. We propose that VEGF synthesized by astrocytes could be involved in the
      guidance of neural progenitors to neurogenic niches and that IQGAP1 is an
      effector of the VEGF-dependent migratory signal.

PMID- 17460086
TI  - Subnanometer fusion pores in spontaneous exocytosis of peptidergic vesicles.
AB  - Kiss-and-run exocytosis, consisting of reversible fusion between the vesicle
      membrane and the plasma membrane, is considered to lead to full fusion after
      stimulation of vesicles containing classical transmitters. However, whether this
      is also the case in the fusion of peptidergic vesicles is unknown. Previously, we
      have observed that spontaneous neuropeptide discharge from a single vesicle is
      slower than stimulated release, because of the kinetic constraints of fusion pore
      opening. To explore whether slow spontaneous release also reflects a relatively
      narrow fusion pore, we analyzed the permeation of FM 4-64 dye and HEPES molecules
      through spontaneously forming fusion pores in lactotroph vesicles expressing
      synaptopHluorin, a pH-dependent fluorescent fusion marker. Confocal imaging
      showed that half of the spontaneous exocytotic events exhibited fusion pore
      openings associated with a change in synaptopHluorin fluorescence but were
      impermeable to FM 4-64 and HEPES. Together with membrane capacitance
      measurements, these findings indicate an open fusion pore diameter <0.5 nm, much
      smaller than the neuropeptides. In stimulated cells, >70% of exocytotic events
      exhibited a larger, FM 4-64-permeable pore (>1 nm). Interestingly, capacitance
      measurements showed that the majority of exocytotic events in spontaneous and
      stimulated conditions were transient. Stimulation increased the frequency of
      transient events and the fusion pore dwell time but decreased the fraction of
      events with lowest measurable fusion pore. Kiss-and-run is the predominant mode
      of exocytosis in resting and in stimulated peptidergic vesicles. Stimulation
      prolongs the effective opening of the fusion pore and expands its primary
      subnanometer diameter to enable hormone secretion without full fusion.

PMID- 17460085
TI  - The novel GTPase Rit differentially regulates axonal and dendritic growth.
AB  - The Rit GTPase is widely expressed in developing and adult nervous systems, and
      our previous data with pheochromocytoma cells implicate Rit signaling in NGF
      induced neurite outgrowth. In this study, we investigated a role for Rit in
      neuronal morphogenesis. Expression of a dominant-negative (dn) Rit mutant in
      hippocampal neurons inhibited axonal growth but potentiated dendritic growth.
      Conversely, a constitutively active (ca) Rit mutant promoted axonal growth but
      inhibited dendritic growth. Dendritogenesis is regulated differently in
      sympathetic neurons versus hippocampal neurons in that sympathetic neurons
      require NGF and bone morphogenetic proteins (BMPs) to trigger dendritic growth.
      Despite these differences, dnRit potentiated and caRit blocked BMP7-induced
      dendritic growth in sympathetic neurons. Biochemical studies indicated that BMP7
      treatments that caused dendritic growth also decreased Rit GTP loading.
      Additional studies demonstrate that caRit increased extracellular signal
      regulated kinase 1/2 (ERK1/2) phosphorylation and pharmacological inhibition of
      MEK1 (mitogen-activated protein kinase/ERK 1) blocked the axon-promoting and
      dendrite-inhibiting effects of caRit. These observations suggest that Rit is a
      convergence point for multiple signaling pathways and it functions to promote
      axonal growth but inhibit dendritic growth via activation of ERK1/2. Modulation
      of the activational status of Rit may therefore represent a generalized mechanism
      across divergent neuronal cell types for regulating axonal versus dendritic
      growth modes.

PMID- 17460087
TI  - Prelimbic/infralimbic inactivation impairs memory for multiple task switches, but
      not flexible selection of familiar tasks.
AB  - Behavioral flexibility, in the form of strategy switching or set shifting, helps
      animals cope with changing contingencies in familiar environments. The prelimbic
      (PL) and infralimbic (IL) regions of the rat prefrontal cortex (PFC) contribute
      to this ability so that rats trained to use one strategy have difficulty learning
      a new one if the PL/IL is inactivated. Thus, the PL/IL mediates learning new
      tasks in place of old ones, but it may also be required to switch between
      familiar tasks. To test this hypothesis, we trained rats to perform multiple task
      switches on a plus-shaped maze, alternating between two familiar tasks. Muscimol
      inactivation of the PL/IL never impaired switch acquisition, but did impair
      memory for the recently acquired switch 24 h later. Additional experiments
      determined that control rats continued to perform the new task 24 h after a
      switch, but rats with PL/IL inactivation had impaired memory and performed the
      same task that was learned before inactivation. This impairment was observed in
      multiple switches, demonstrating that PL/IL activity was required to remember
      which of two familiar tasks was most recently successful. After many switches,
      however, muscimol no longer impaired performance, and both saline- and muscimol
      infused rats appeared to use immediate task contingencies rather than memory to
      select among familiar tasks. This strategy may account for the decreased effect
      of PL/IL inactivation observed after extensive training. Thus, although PL/IL
      activity contributed to memory for multiple task switches, it was not required
      for flexibly selecting among highly familiar tasks.

PMID- 17460088
TI  - Ambient light regulates sodium channel activity to dynamically control retinal
      signaling.
AB  - The retinal network increases its sensitivity in low-light conditions to detect
      small visual inputs and decreases its sensitivity in bright-light conditions to
      prevent saturation. However, the cellular mechanisms that adjust visual signaling
      in the retinal network are not known. Here, we show that voltage-gated sodium
      channels in bipolar cells dynamically control retinal light sensitivity. In dim
      conditions, sodium channels amplified light-evoked synaptic responses mediated by
      cone pathways. Conversely, in bright conditions, sodium channels were inactivated
      by dopamine released from amacrine cells, and they did not amplify synaptic
      inputs, minimizing signal saturation. Our findings demonstrate that bipolar cell
      sodium channels mediate light adaptation by controlling retinal signaling gain.

PMID- 17460089
TI  - Ethanol inhibits persistent activity in prefrontal cortical neurons.
AB  - Cognitive functions supported by neurons in the prefrontal cortex (PFC) are
      disrupted by acute and chronic exposure to alcohol, yet little is known about the
      mechanisms that underlie these effects. In the present study, in vivo and in
      vitro electrophysiology was used to determine the effects of ethanol on neuronal
      firing and network patterns of persistent activity in PFC neurons. In vivo,
      ethanol (0.375-3.5 g/kg) dose-dependently reduced spike activity in the PFC
      measured with multielectrode extracellular recording in the anesthetized rat. In
      an in vitro coculture system containing slices of PFC, hippocampus, and ventral
      tegmental area (VTA), ethanol (25-100 mM) decreased persistent activity of PFC
      neurons, but had little effect on firing evoked by direct current injection.
      Persistent activity was often enhanced after ethanol washout and this effect was
      maintained in cultures lacking the VTA. A low concentration of the NMDA
      antagonist APV (5 microM) mimicked the inhibition of ethanol of persistent
      activity with no change in activity after washout. Ethanol inhibition of
      spontaneous and VTA-evoked persistent activity was enhanced by the D1 dopamine
      receptor antagonist SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5
      tetrahydro-1H-3-benzazepine hydrochloride]. The results of this study show that
      ethanol inhibits persistent activity and spike firing of PFC neurons and that the
      degree of ethanol inhibition may be influenced by D1 receptor tone. Ethanol
      induced alterations in the activity of deep-layer cortical neurons may underlie
      some of the behavioral effects associated with ethanol intake.

PMID- 17460090
TI  - Differential regulation of action potential- and metabotropic glutamate receptor
      induced Ca2+ signals by inositol 1,4,5-trisphosphate in dopaminergic neurons.
AB  - Ca2+ signals associated with action potentials (APs) and metabotropic glutamate
      receptor (mGluR) activation exert distinct influences on neuronal activity and
      synaptic plasticity. However, it is not clear how these two types of Ca2+ signals
      are differentially regulated by neurotransmitter inputs in a single neuron. We
      investigated this issue in dopaminergic neurons of the ventral midbrain using
      brain slices. Intracellular Ca2+ was assessed by measuring Ca2+-sensitive K+
      currents or imaging the fluorescence of Ca2+ indicator dyes. Tonic activation of
      metabotropic neurotransmitter receptors (mGluRs, alpha1 adrenergic receptors, and
      muscarinic acetylcholine receptors), attained by superfusion of agonists or weak,
      sustained (approximately 1 s) synaptic stimulation, augmented AP-induced Ca2+
      transients. In contrast, Ca2+ signals elicited by strong, transient (50-200 ms)
      activation of mGluRs with aspartate iontophoresis were suppressed by superfusion
      of agonists. These opposing effects on Ca2+ signals were both mediated by an
      increase in intracellular inositol 1,4,5-trisphosphate (IP3) levels, because they
      were blocked by heparin, an IP3 receptor antagonist, and reproduced by photolytic
      application of IP3. Evoking APs repetitively at low frequency (2 Hz) caused
      inactivation of IP3 receptors and abolished IP3 facilitation of single AP-induced
      Ca2+ signals, whereas facilitation of Ca2+ signals triggered by bursts of APs
      (five at 20 Hz) was attenuated by less than half. We further obtained evidence
      suggesting that the psychostimulant amphetamine may augment burst-induced Ca2+
      signals via both depression of basal firing and production of IP3. We propose
      that intracellular IP3 tone provides a mechanism to selectively amplify burst
      induced Ca2+ signals in dopaminergic neurons.

PMID- 17460092
TI  - Globozoospermia: is there a role for varicocele repair?

PMID- 17460093
TI  - Interviews with andrologists (part 3). Interview by Sarika Saraswati.

PMID- 17460091
TI  - Inactivation of Arx, the murine ortholog of the X-linked lissencephaly with
      ambiguous genitalia gene, leads to severe disorganization of the ventral
      telencephalon with impaired neuronal migration and differentiation.
AB  - ARX loss-of-function mutations cause X-linked lissencephaly with ambiguous
      genitalia (XLAG), a severe neurological condition that results in profound brain
      malformations, including microcephaly, absence of corpus callosum, and impairment
      of the basal ganglia. Despite such dramatic defects, their nature and origin
      remain largely unknown. Here, we used Arx mutant mice as a model to characterize
      the cellular and molecular mechanisms underlying the basal ganglia alterations.
      In these animals, the early differentiation of this tissue appeared normal,
      whereas subsequent differentiation was impaired, leading to the periventricular
      accumulation of immature neurons in both the lateral ganglionic eminence and
      medial ganglionic eminence (MGE). Both tangential migration toward the cortex and
      striatum and radial migration to the globus pallidus and striatum were greatly
      reduced in the mutants, causing a periventricular accumulation of NPY+ or
      calretinin+ neurons in the MGE. Arx mutant neurons retained their differentiation
      potential in vitro but exhibited deficits in morphology and migration ability.
      These findings imply that cell-autonomous defects in migration underlie the
      neuronal localization defects. Furthermore, Arx mutants lacked a large fraction
      of cholinergic neurons and displayed a strong impairment of thalamocortical
      projections, in which major axon fiber tracts failed to traverse the basal
      ganglia. Altogether, these results highlight the critical functions of Arx in
      promoting neural migration and regulating basal ganglia differentiation in mice,
      consistent with the phenotype of XLAG patients.

PMID- 17460094
TI  - Cryosurvival and in vitro fertilizing capacity postthaw is improved when boar
      spermatozoa are frozen in the presence of seminal plasma from good freezer boars.
AB  - The study evaluated the protective effect of seminal plasma (SP) added to
      freezing extender against cryopreservation injuries to boar spermatozoa. Pooled
      sperm-rich fractions collected from 9 fertile boars were frozen in 0.5-mL straws
      after being extended in a conventional freezing extender either alone or
      supplemented with 5% of SPs (SP1-SP4) collected from the sperm-rich fractions
      (diluted 1:1, vol/vol, in Beltsville Thawing Solution extender) from 4 boars (1
      4) with known sperm cryosurvival (poor, moderate, and good sperm freezers).
      Cryopreservation injuries were assessed in terms of postthaw sperm motility
      (assessed by computer-assisted sperm analysis), viability (plasma membrane and
      acrosome integrity assessed simultaneously by flow cytometry), membrane lipid
      peroxidation (malondialdehyde [MDA] production), and the ability of thawed
      spermatozoa to fertilize in vitro-matured homologous oocytes. The addition of SP
      from good sperm freezers (SP3 and SP4) improved (P < .01) the motility and
      viability of thawed spermatozoa without any influence on MDA production.
      Moreover, SP from good sperm freezers also increased (P < .05) the percentage of
      penetrated (SP3) and polyspermic oocytes (SP4) with respect to the control.
      Neither the total amount of SP proteins, protein profiles, nor antioxidant
      capacity of the different SPs were related to the various
      cryosurvival/fertilizing capacities of the processed spermatozoa.

PMID- 17460095
TI  - 7alpha-methyl-19-nortestosterone (MENT) vs testosterone in combination with
      etonogestrel implants for spermatogenic suppression in healthy men.
AB  - Testosterone with a progestogen can suppress spermatogenesis for contraception.
      The synthetic androgen 7alpha-methyl-19-nortestosterone (MENT) may offer
      advantages because it is resistant to 5alpha-reduction and is therefore less
      active at the prostate. This study aimed to investigate MENT implants in
      combination with etonogestrel on spermatogenesis, gonadotropins, and androgen
      dependent tissues in comparison with a testosterone/etonogestrel regimen. Healthy
      men (n = 29) were recruited and randomized to receive 2 etonogestrel implants
      with either 600-mg testosterone pellets repeated every 12 weeks or 2 MENT
      implants for up to 48 weeks. Testosterone concentrations in the testosterone
      group remained in the normal range. Subjects with 2 MENT implants showed peak
      MENT levels at 4 weeks with testosterone concentrations of 2 nmol/L. Sperm
      concentrations fell rapidly to less than 1 x 10(6)/mL at 12 weeks in 8 of 10
      subjects in the MENT group and 13 of 16 subjects in the testosterone group with
      equally suppressed gonadotropins. Thereafter, suppression was not maintained in
      the MENT group, and 6 men noted loss of libido. Fourteen men completed 48 weeks
      of testosterone treatment, and all became azoospermic. Hemoglobin concentrations
      rose, and high density lipoprotein-cholesterol (HDL-C) fell in both groups. The
      MENT group showed a fall in prostate-specific antigen with no change in bone
      mass. MENT with a progestogen can achieve rapid suppression of spermatogenesis
      similar to testosterone, but this promising result was not sustained due to a
      decline in MENT release from the implants. This dose of testosterone, compared
      with previous studies using a lower dose with a higher dose of etonogestrel, had
      nonreproductive side effects without any increase in spermatogenic suppression.
      These data indicate the importance of the doses of progestogen and testosterone
      for optimum spermatogenic suppression while minimizing side effects.

PMID- 17460096
TI  - Calmodulin and CaMKII in the sperm principal piece: evidence for a motility
      related calcium/calmodulin pathway.
AB  - Both cyclic AMP (cAMP)/protein kinase A (PKA) and calcium (Ca(2+)) signaling
      pathways are known to be involved in the regulation of motility in mammalian
      sperm. Calmodulin (CaM) is a ubiquitous Ca(2+) sensor that has been implicated in
      the acrosome reaction. In this report, we identify an insoluble pool of CaM in
      sperm and show that the protein, in addition to its presence in the acrosome, is
      found in the principal piece of the flagellum. These findings are consistent
      with, though not proof of, the presence of a pool of CaM in the fibrous sheath.
      The Ca(2+)/CaM-dependent protein kinase IIbeta (CaMKIIbeta), which is a
      downstream target of Ca(2+)/CaM, similarly localizes to the principal piece. In
      addition, we confirm earlier reports that a CaM inhibitor decreases sperm
      motility. However, we find that this inhibition can be largely reversed by
      stimulation of PKA if substrates for oxidative respiration are present in the
      medium. Our results suggest that the Ca(2+)/CaM/CaMKII signaling pathway in the
      sperm principal piece is involved in regulating sperm motility, and that this
      pathway functions either in parallel with or upstream of the cAMP/PKA pathway.

PMID- 17460097
TI  - Ability of abnormally-shaped human spermatozoa to adhere to and penetrate zona
      free hamster eggs: correlation with sperm morphology and postincubation motility.
AB  - A body of evidence indicates that morphologically abnormal human spermatozoa may
      exhibit impaired ability to fertilize. Yet teratospermia has widely varying
      etiologies, including associations with varicoceles, following fever, cigarette
      smoking, and exposure to polychlorinated biphenyls. Abnormalities of sperm shape
      in mice have also been shown to be associated with autosomal gene mutations.
      These varying causes of teratospermia could have different molecular consequences
      reflected in altered sperm function. We studied the ability of morphologically
      abnormal human sperm to penetrate zona-free hamster eggs as a measure of their
      ability to undergo an acrosome reaction and gamete membrane fusion. Motile sperm
      from ejaculates containing 15% normal sperm or less, as judged by World Health
      Organization (1999) criteria, were recovered by ISolate density centrifugation
      and capacitated by overnight incubation. Zona-free hamster eggs were inseminated
      with 1 x 10(6) motile capacitated cells and scored for sperm penetration after 3
      hours of coincubation. A significant trend was found between the percent of
      abnormal spermatozoa within the ejaculate and impaired egg-penetrating ability,
      reflected in the percent of eggs penetrated, the number of penetrating sperm per
      egg, and the number of sperm adherent to the oolemma. Because only acrosome
      reacted human spermatozoa adhere to the oolemma, these results support the notion
      that abnormally shaped sperm may exhibit an impaired ability to undergo an
      acrosome reaction. A correlation was also noted between the loss of motility of
      sperm following overnight incubation and impairment of their ability to undergo
      gamete membrane fusion. These results confirm prior findings at the level of the
      zona pellucida that abnormally shaped sperm exhibit functional abnormalities.
      However, a wide variation was observed between men in the behavior of such sperm,
      including occasionally high rates of egg penetration. These observations suggest
      that assessment of morphology may be an unreliable measure, for the individual,
      of sperm fertilizing ability and emphasize that sperm function testing is an
      important part of the evaluation of teratospermia.

PMID- 17460098
TI  - Preparation of anticipatory postural adjustments prior to stepping.
AB  - Step initiation involves anticipatory postural adjustments (APAs) that propel the
      body mass forward and laterally before the first step. This study used a startle
      like acoustic stimulus (SAS) and transcranial magnetic stimulation (TMS) to
      examine the preparation of APAs before forward stepping. After an instructed
      delay period, subjects initiated forward steps in reaction to a visual "go" cue.
      TMS or SAS was delivered before (-1,400 or -100 ms), on (0 ms), or after (+100 ms
      for TMS, +200 ms for SAS) the imperative "go" cue. Ground reaction forces and
      electromyographic activity were recorded. In control trials, the mean reaction
      time was 217 +/- 38 ms. In contrast, the SAS evoked APAs that had an average
      onset of 110 +/- 54 ms, whereas the incidence, magnitude, and duration of the APA
      increased as the stimulus timing approached the "go" cue. A facilitation of motor
      evoked potentials in the initial agonist muscle was observed only when TMS was
      applied at +100 ms. These findings indicate that there was an initial phase of
      movement preparation during which the APA-stepping sequence was progressively
      assembled, and that this early preparation did not involve the corticomotor
      pathways activated by TMS. The subsequent increase in corticomotor excitability
      between the imperative stimulus and onset of the APA suggests that corticospinal
      pathways contribute to the voluntary initiation of the prepared APA-stepping
      sequence. These findings are consistent with a feedforward mode of neural control
      whereby the motor sequence, including the associated postural adjustments, is
      prepared before voluntary movement.

PMID- 17460099
TI  - Subthalamic stimulation and neuronal activity in the substantia nigra in
      Parkinson's disease.
AB  - High-frequency stimulation of the subthalamic nucleus (STN) is an effective
      treatment for severe forms of Parkinson's disease (PD). To study the effects of
      high-frequency STN stimulation on one of the main output pathways of the basal
      ganglia, single-unit recordings of the neuronal activity of the substantia nigra
      pars reticulata (SNr) were performed before, during, and after the application of
      STN electrical stimulation in eight PD patients. During STN stimulation at 14 Hz,
      no change in either the mean firing rate or the discharge pattern of SNr neurons
      was observed. STN stimulation at 140 Hz decreased the mean firing rate by 64% and
      the mean duration of bursting mode activity of SNr neurons by 70%. The SNr
      residual neuronal activity during 140-Hz STN stimulation was driven by the STN
      stimulation. How the decrease in rate and modification of firing pattern of SNr
      evoked neural activity, during high-frequency STN stimulation, contribute to the
      improvement of parkinsonian motor disability remains to be elucidated.

PMID- 17460100
TI  - Reduced 5-HT1A- and GABAB receptor function in dorsal raphe neurons upon chronic
      fluoxetine treatment of socially stressed rats.
AB  - Autoinhibitory serotonin 1A receptors (5-HT(1A)) in dorsal raphe nucleus (DRN)
      have been implicated in chronic depression and in actions of selective serotonin
      reuptake inhibitors (SSRI). Due to experimental limitations, it was never studied
      at single-cell level whether changes in 5-HT(1A) receptor functionality occur in
      depression and during SSRI treatment. Here we address this question in a social
      stress paradigm in rats that mimics anhedonia, a core symptom of depression. We
      used whole cell patch-clamp recordings of 5-HT- and baclophen-induced G-protein
      coupled inwardly rectifying potassium (GIRK) currents as a measure of 5-HT(1A)-
      and GABA(B) receptor functionality. 5-HT(1A)- and GABA(B) receptor-mediated GIRK
      currents were not affected in socially stressed rats, suggesting that there was
      no abnormal (auto)inhibition in the DRN on social stress. However, chronic
      fluoxetine treatment of socially stressed rats restored anticipatory behavior and
      reduced the responsiveness of 5-HT(1A) receptor-mediated GIRK currents. Because
      GABA(B) receptor-induced GIRK responses were also suppressed, fluoxetine does not
      appear to desensitize 5-HT(1A) receptors but rather one of the downstream
      components shared with GABA(B) receptors. This fluoxetine effect on GIRK currents
      was also present in healthy animals and was independent of the animal's
      "depressed" state. Thus our data show that symptoms of depression after social
      stress are not paralleled by changes in 5-HT(1A) receptor signaling in DRN
      neurons, but SSRI treatment can alleviate these behavioral symptoms while acting
      strongly on the 5-HT(1A) receptor signaling pathway.

PMID- 17460101
TI  - Plasticity in the rat posterior auditory field following nucleus basalis
      stimulation.
AB  - Classical conditioning paradigms have been shown to cause frequency-specific
      plasticity in both primary and secondary cortical areas. Previous research
      demonstrated that repeated pairing of nucleus basalis (NB) stimulation with a
      tone results in plasticity in primary auditory cortex (A1), mimicking the changes
      observed after classical conditioning. However, few studies have documented the
      effects of similar paradigms in secondary cortical areas. The purpose of this
      study was to quantify plasticity in the posterior auditory field (PAF) of the rat
      after NB stimulation paired with a high-frequency tone. NB-tone pairing increased
      the frequency selectivity of PAF sites activated by the paired tone. This
      frequency-specific receptive field size narrowing led to a reorganization of PAF
      such that responses to low- and mid-frequency tones were reduced by 40%.
      Plasticity in A1 was consistent with previous studies -- pairing a high-frequency
      tone with NB stimulation expanded the high-frequency region of the frequency map.
      Receptive field sizes did not change, but characteristic frequencies in A1 were
      shifted after NB-tone pairing. These results demonstrate that experience
      dependent plasticity can take different forms in both A1 and secondary auditory
      cortex.

PMID- 17460102
TI  - Functional circuitry for peripheral suppression in Mammalian Y-type retinal
      ganglion cells.
AB  - A retinal ganglion cell receptive field is made up of an excitatory center and an
      inhibitory surround. The surround has two components: one driven by horizontal
      cells at the first synaptic layer and one driven by amacrine cells at the second
      synaptic layer. Here we characterized how amacrine cells inhibit the center
      response of on- and off-center Y-type ganglion cells in the in vitro guinea pig
      retina. A high spatial frequency grating (4-5 cyc/mm), beyond the spatial
      resolution of horizontal cells, drifted in the ganglion cell receptive field
      periphery to stimulate amacrine cells. The peripheral grating suppressed the
      ganglion cell spiking response to a central spot. Suppression of spiking was
      strongest and observed most consistently in off cells. In intracellular
      recordings, the grating suppressed the subthreshold membrane potential in two
      ways: a reduced slope (gain) of the stimulus-response curve by approximately 20
      30% and, in off cells, a tonic approximately 1-mV hyperpolarization. In voltage
      clamp, the grating increased an inhibitory conductance in all cells and
      simultaneously decreased an excitatory conductance in off cells. To determine
      whether center response inhibition was presynaptic or postsynaptic (shunting), we
      measured center response gain under voltage-clamp and current-clamp conditions.
      Under both conditions, the peripheral grating reduced center response gain
      similarly. This result suggests that reduced gain in the ganglion cell
      subthreshold center response reflects inhibition of presynaptic bipolar
      terminals. Thus amacrine cells suppressed ganglion cell center response gain
      primarily by inhibiting bipolar cell glutamate release.

PMID- 17460103
TI  - Role of the cerebellum in externally paced rhythmic finger movements.
AB  - Several studies have suggested that the cerebellum has an important role in
      timing of subsecond intervals. Previous studies using transcranial magnetic
      stimulation (TMS) to test this hypothesis directly have produced inconsistent
      results. Here we used 1-Hz repetitive TMS (rTMS) for 10 min over the right or
      left cerebellar hemisphere to interfere transiently with cerebellar processing to
      assess its effect on the performance of a finger-tapping task. Subjects tapped
      with their right index finger for 1 min (synchronization phase) with an auditory
      or visual cue at 0.5, 1, or 2 Hz; they continued for a further 1 min at the same
      rate with no cues (continuation phase). The blocks of trials were performed in a
      random order. rTMS of the cerebellum ipsilateral to the movement increased the
      variability of the intertap interval but only for movements at 2 Hz that were
      made while subjects were synchronizing with an auditory cue. There was no effect
      on the continuation phase of the task when the cues were no longer present or on
      synchronization with a visual cue. Similar results were seen after stimulation
      over the contralateral dorsal premotor cortex but not after rTMS over
      supplementary motor area. There was no effect after rTMS over the ipsilateral
      right cervical nerve roots or over the ipsilateral primary motor cortex. The
      results support the hypothesis of neural network for event-related timing in the
      subsecond range that involves a cerebellar-premotor network.

PMID- 17460104
TI  - Divided attention impairs human motor adaptation but not feedback control.
AB  - When humans experience externally induced errors in a movement, the motor
      system's feedback control compensates for those errors within the movement. The
      motor system's predictive control then uses information about those errors to
      inform future movements. The role of attention in these two distinct motor
      processes is unclear. Previous experiments have revealed a role for attention in
      motor learning over the course of many movements; however, these experimental
      paradigms do not determine how attention influences within-movement feedback
      control versus across-movement adaptation. Here we develop a dual-task paradigm,
      consisting of movement and audio tasks, which can differentiate and expose
      attention's role in these two processes of motor control. Over the course of
      several days, subjects performed horizontal reaching movements, with and without
      the audio task; movements were occasionally subjected to transient force
      perturbations. On movements with a force perturbation, subjects compensated for
      the force-induced movement errors, and on movements immediately after the force
      perturbation subjects exhibited adaptation. On every movement trial, subjects
      performed a two-tone frequency-discrimination task. The temporal specificity of
      the frequency-discrimination task allowed us to divide attention within and
      across movements. We find that divided attention did not impair the within
      movement feedback control of the arm, but did reduce subsequent movement
      adaptation. We suggest that the secondary task interfered with the encoding and
      transformation of errors into changes in predictive control.

PMID- 17460105
TI  - Ion channel compartments in photoreceptors: evidence from salamander rods with
      intact and ablated terminals.
AB  - Vertebrate photoreceptors are highly polarized sensory cells in which several
      different ionic currents have been characterized. In the present study we used
      whole cell voltage-clamp and optical imaging techniques, the former combined with
      microsurgical manipulations, and simultaneous recording of membrane current and
      intracellular calcium signals to investigate the spatial distribution of ion
      channels within isolated salamander rods. In recordings from intact rods with
      visible terminals, evidence for five previously identified ionic currents was
      obtained. These include two Ca(2+)-dependent, i.e., a Ca(2+)-dependent chloride
      current [I(Cl(Ca))] and a large-conductance Ca(2+)- and voltage-dependent K(+) or
      BK current [I(K(Ca))], and three voltage-dependent currents, i.e., a delayed
      rectifier type current [I(K(V))], a hyperpolarization-activated cation current
      (I(h)), and a dihydropyridine-sensitive L-type calcium current (I(Ca)). Of these,
      I(Cl(Ca)) was highly correlated with the presence of a terminal; rods with
      visible terminals expressed I(Cl(Ca)) without exception (n = 125), whereas
      approximately 71% of rods (40/56) without visible terminals lacked I(Cl(Ca)).
      More significantly, I(Cl(Ca)) was absent from all rods (n = 33) that had their
      terminals ablated, and recordings from the same cell before and after terminal
      ablation led, in all cases (n =10), to the loss of I(Cl(Ca)). In contrast,
      I(K(Ca)), I(K(V)), and I(h) remained largely intact after terminal ablation,
      suggesting that they arose principally from ion channels located in the soma
      and/or inner segment. The outward I(K)((Ca)) in terminal-ablated rods was
      reversibly suppressed on "puffing" a Ca(2+)-free extracellular solution over the
      soma and was appreciably enhanced by the L-type Ca(2+) channel agonist, Bay K
      8644 (0.1-2 microM). These data indicate that rod photoreceptors possess discrete
      targeting mechanisms that preferentially sort ion channels mediating I(Cl(Ca)) to
      the terminal.

PMID- 17460106
TI  - Postural responses evoked by platform pertubations are dominated by continuous
      feedback.
AB  - Is human balance control dominated by time invariant continuous feedback
      mechanisms or do noncontinuous mechanisms play a significant role like
      intermittent control? The goal of this paper is to quantify how much of the
      postural responses evoked by pseudorandom external periodic perturbations can be
      explained by continuous time invariant feedback control. Nine healthy subjects
      participated in this study. Center of mass and ankle torque responses were
      elicited by periodic platform perturbations in forward-backward directions
      containing energy in the 0.06- to 4.5-Hz frequency band. Subjects had their eyes
      open (EO) or eyes closed (EC). Responses were decomposed into a periodic
      component and a remnant (stochastic) component using spectral analysis. It is
      concluded that periodic responses can explain most of the evoked responses,
      although the remnant power spectral densities (PSDs) were significant especially
      for slow responses (<0.2 Hz) and largest for EC. The found remnant PSD did depend
      on the sensory condition but not on the platform perturbation amplitude. The
      ratio of the body sway and ankle torque remnant PSD reflects the body dynamics.
      Both findings are consistent with the idea that estimation of body orientation is
      part of a continuous feedback loop and that (stochastic) estimation errors
      increase when one source of sensory information is removed. The findings are not
      consistent with the idea that discrete or discontinuous intermittent feedback
      mechanisms significantly shape postural responses.

PMID- 17460107
TI  - GABAergic pump cells of solitary tract nucleus innervate retrotrapezoid nucleus
      chemoreceptors.
AB  - The retrotrapezoid nucleus (RTN) contains central respiratory chemoreceptors that
      are inhibited by activation of slowly adapting pulmonary stretch receptors
      (SARs). Here we examine whether RTN inhibition by lung inflation could be
      mediated by a direct projection from SAR second-order neurons (pump cells). Pump
      cells (n = 56 neurons, 13 rats) were recorded in the nucleus of solitary tract
      (NTS) of halothane-anesthetized rats with intact vagus nerves. Pump cells had
      discharges that coincided with lung inflation as monitored by the tracheal
      pressure. Their activity increased when end-expiratory pressure was raised and
      stopped instantly when ventilation was interrupted in expiration. Many pump cells
      could be antidromically activated from RTN (12/36). Nine of those were labeled
      with biotinamide. Of these nine cells, eight contained glutamic acid
      decarboxylase 67 (GAD67) mRNA and seven were found to reside in the lower half of
      the interstitial subnucleus of NTS (iNTS). Using the retrograde tracer cholera
      toxin-B, we confirmed that neurons located in or close to iNTS innervate RTN (two
      rats). Many such neurons contained GAD67 mRNA and a few contained glycine
      transporter2 (GLYT2) mRNA. Anterograde tract tracing with biotinylated
      dextranamide (four rats) applied to iNTS also confirmed that this region
      innervates RTN by a predominantly GABAergic projection. This work confirms that
      many rat NTS pump cells are located in and around the interstitial subnucleus at
      area postrema level. We demonstrate that a GABAergic subset of these pump cells
      innervates the RTN region. We conclude that these inhibitory neurons probably
      contact RTN chemoreceptors and mediate their inhibition by lung inflation.

PMID- 17460108
TI  - Temporal development of cyclic nucleotide-gated and Ca2+ -activated Cl- currents
      in isolated mouse olfactory sensory neurons.
AB  - A Ca(2+)-activated Cl(-) current constitutes a large part of the transduction
      current in olfactory sensory neurons. The binding of odorants to olfactory
      receptors in the cilia produces an increase in cAMP concentration; Ca(2+) enters
      into the cilia through CNG channels and activates a Cl(-) current. In intact
      mouse olfactory sensory neurons little is known about the kinetics of the Ca(2+)
      activated Cl(-) current. Here, we directly activated CNG channels by flash
      photolysis of caged cAMP or 8-Br-cAMP and measured the current response with the
      whole cell voltage-clamp technique in mouse neurons. We measured multiphasic
      currents in the rising phase of the response at -50 mV. The current rising phase
      became monophasic in the absence of extracellular Ca(2+), at +50 mV, or when most
      of the intracellular Cl(-) was replaced by gluconate to shift the equilibrium
      potential for Cl(-) to -50 mV. These results show that the second phase of the
      current in mouse intact neurons is attributed to a Cl(-) current activated by
      Ca(2+), similarly to previous results on isolated frog cilia. The percentage of
      the total saturating current carried by Cl(-) was estimated in two ways: 1) by
      measuring the maximum secondary current and 2) by blocking the Cl(-) channel with
      niflumic acid. We estimated that in the presence of 1 mM extracellular Ca(2+) and
      in symmetrical Cl(-) concentrations the Cl(-) component can constitute up to 90%
      of the total current response. These data show how to unravel the CNG and Ca(2+)
      activated Cl(-) component of the current rising phase.

PMID- 17460109
TI  - Rapid and precise control of sniffing during olfactory discrimination in rats.
AB  - Olfactory perception relies on an active sampling process, sniffing, to rapidly
      deliver odorants from the environment to the olfactory receptors. The respiration
      cycle strongly patterns the flow of information into the olfactory systems, but
      the behavioral significance of particular sniffing patterns is not well
      understood. Here, we monitored the frequency and timing of nasal respiration in
      rats performing an odor-mixture-discrimination task that allowed us to test
      subjects near psychophysical limits and to quantify the precise timing of their
      behavior. We found that respiration frequencies varied widely from 2 to 12 Hz,
      but odor discrimination was dependent on 6- to 9-Hz sniffing: rats almost always
      entered and maintained this frequency band during odor sampling and their
      accuracy on difficult discrimination dropped when they did not. Moreover, the
      switch from baseline respiration to sniffing occurred not in response to odor
      delivery but in anticipation of odor sampling and was executed rapidly, almost
      always within a single cycle. Interestingly, rats also switched from respiration
      to rapid sniffing in anticipation of reward delivery, but in a distinct frequency
      band, 9-12 Hz. These results demonstrate the speed and precision of control over
      respiration and its significance for olfactory behavioral performance.

PMID- 17460110
TI  - Endocrine-related resources from the National Institutes of Health.

PMID- 17460111
TI  - Extended culture enhances sensitivity of a gamma interferon assay for latent
      Mycobacterium tuberculosis infection.
AB  - To test the hypothesis that prolonged culture would enhance the sensitivity of
      latent tuberculosis detection by a gamma interferon release assay, blood samples
      from 33 household contacts of Gambian tuberculosis patients were stimulated with
      Mycobacterium tuberculosis-specific antigens. After 24 h of culture, 66% were
      positive, compared to 93% after 6 days of culture.

PMID- 17460112
TI  - Fruit-specific expression of the human immunodeficiency virus type 1 tat gene in
      tomato plants and its immunogenic potential in mice.
AB  - The human immunodeficiency virus type 1 (HIV-1) Tat protein is considered a
      potential candidate vaccine antigen. In an effort to design a strategy for
      noninvasive vaccination against HIV-1, we developed transgenic tomatoes
      expressing the Tat protein. Two independent plants testing positive in transgene
      detection analysis were selected and grown to maturity. Monoclonal antibodies
      against Tat recognized a protein of the expected size. Interestingly, expression
      of Tat seemed to be toxic to the plant, as in all cases the fruit exhibited
      underdeveloped reproductive structures and no seeds. Nine groups of 10 pathogen
      free BALB/c male mice were primed either orally, intraperitoneally, or
      intramuscularly with 10 mg of tomato fruit extract derived from transgenic or
      wild-type plants and with 10 microg of Tat86 recombinant protein. Mice were
      immunized at days 0, 14, and 28, and given boosters after 15 weeks; sera were
      drawn 7 days after each booster, and the antibody titer was determined by enzyme
      linked immunosorbent assay. All three immunization approaches induced the
      development of a strong anti-Tat immunological response, which increased over
      time. Isotype subclass determination showed the presence of mucosal
      (immunoglobulin A) immunity soon after the beginning of the oral immunization
      protocol, and the data were confirmed by the presence of anti-Tat antibodies in
      fecal pellets and in vaginal washes. We also demonstrated that sera from
      immunized mice inhibited with high efficiency recombinant Tat-dependent
      transactivation of the HIV-1 long terminal repeat promoter. This neutralization
      activity might be relevant for the suppression of extracellular Tat activities,
      which play an important role in HIV disease development.

PMID- 17460113
TI  - Immunization with PspA incorporated into a poly(ethylene oxide) matrix elicits
      protective immunity against Streptococcus pneumoniae.
AB  - CBA/N mice were immunized with PspA in a poly(ethylene oxide) matrix to examine
      its ability to deliver the antigen and modulate the immune response. All mice
      receiving PspA in the matrix survived a lethal pneumococcal challenge and had
      serum anti-PspA antibody levels statistically higher than mice receiving PspA
      alone (P < 0.009).

PMID- 17460114
TI  - Exocytosis of Neutrophil Formyl peptide receptor-like 1 (fPRL1) results in
      downregulation of cytoplasmic fPRL1 in patients with purulent dermatitis.
AB  - N-Formyl peptide receptor-like 1 (fPRL1) is a member of the chemoattractant
      subfamily of G protein-coupled receptors and plays a key role in inflammation via
      chemotaxis and the regulation of mediator release from leukocytes. Activated
      fPRL1 has recently been shown to induce a complicated pattern of cellular
      signaling in vitro, but the details of the regulation and alteration of leukocyte
      cellular fPRL1 during inflammation in vivo remain unclear. To clarify the
      alteration of neutrophil fPRL1 during inflammation in vivo, the
      immunohistochemical staining of neutrophil fPRL1 in samples from patients with
      purulent dermatitis was performed. The in vitro morphological alteration of
      neutrophil fPRL1 on cellular membranes by stimulation with N-formylmethionyl
      leucyl-phenylalanine (fMLP) was also examined. Both the cytoplasm and the
      cellular membranes of blood neutrophils stained strongly for fPRL1. On the other
      hand, the cellular membranes of neutrophils in dermatitis tissue stained strongly
      for fPRL1 but the cytoplasm stained weakly. The enhancement of neutrophil fPRL1
      on cellular membranes by stimulation with fMLP indicates the exocytosis of
      neutrophil fPRL1-containing granules. In conclusion, we for the first time
      confirmed the alteration of neutrophil fPRL1 in clinical cases of purulent
      dermatitis. Cytoplasm that was weakly stained and cellular membranes that were
      well stained for fPRL1 were considered to be distinctive features of activated
      neutrophils in purulent dermatitis tissue.

PMID- 17460115
TI  - Milk and serum J5-specific antibody responses, milk production change, and
      clinical effects following intramammary Escherichia coli challenge for J5
      vaccinate and control cows.
AB  - Holstein dairy cows (four J5 vaccinates and four controls) selected for no
      recorded intramammary disease and low somatic cell count (SCC) during the
      previous lactation were challenged by intramammary infusion of Escherichia coli.
      Vaccination with J5 was at 8 weeks and again 4 weeks before the anticipated
      calving date. Cows were challenged at 8 to 16 days in milk (DIM). Shedding of E.
      coli in milk was significantly higher among controls than vaccinates (no
      shedding) from 6 h to 21 h postchallenge. From 21 h to 132 h postchallenge, SCC
      in challenged quarters of controls (5,429,000/ml) was significantly higher than
      that of vaccinates (490,000/ml). On the day after challenge, milk production in
      control cows was 8 kg less, while vaccinates gained 0.5 kg, a significant
      difference. In serum immediately prior to challenge, J5-specific immunoglobulin
      G1 (IgG1) was significantly higher, IgG2 was nearly significantly higher, and IgM
      was the same in J5 vaccinates relative to controls. Vaccinates had proportionally
      more IgG2 in serum postcalving and in the first 12 h following challenge and less
      IgG2 in milk 24 h after challenge than the controls, approaching statistical
      significance. The ratio of J5-specific IgG1 and IgG2 combined compared to IgM was
      significantly higher in vaccinates than in controls in prechallenge serum (ratios
      of 15.8 and 3.2, respectively) and milk (5.0 and 1.3, respectively). Cows with
      higher IgM titers in milk 12 h postchallenge produced significantly less milk.
      Vaccination with J5 was significantly associated with higher production of J5
      specific IgG1 and IgG2 in early lactation, reduced SCC, faster clearance of E.
      coli from milk, and less milk production loss following intramammary challenge.

PMID- 17460116
TI  - Evaluation of two rapid immunochromatographic assays for diagnosis of dengue
      among Vietnamese febrile patients.
AB  - Results from two dengue rapid tests, the PanBio Duo cassette and the SD Bioline
      strip test, were compared to those of enzyme-linked immunosorbent assays (Focus
      Diagnostics) from sera of 200 Vietnamese febrile patients. The PanBio assay was
      superior, with sensitivity and specificity values for acute-phase serum samples
      of 54% and 70% (immunoglobulin M) and 70% and 88% (immunoglobulin G),
      respectively.

PMID- 17460117
TI  - Seroprevalence of selected infectious agents in a free-ranging, low-density lion
      population in the Central Kalahari Game Reserves in Botswana.
AB  - Twenty-one free-ranging Central Kalahari lions (Panthera leo) exhibited a high
      prevalence rate of feline herpesvirus (100%) and feline immunodeficiency virus
      (71.4%). Canine distemper virus and feline calicivirus occurred with a low
      prevalence. All individuals tested negative for feline coronavirus, feline
      parvovirus, feline leukemia virus, Ehrlichia canis, and Anaplasma
      phagocytophilum.

PMID- 17460118
TI  - Single-chain antibody fragment specific for Plasmodium vivax Duffy binding
      protein.
AB  - Phage display of single-chain variable fragment (scFv) antibodies is a powerful
      tool for selecting important, useful, and specific human antibodies. We
      constructed a library from three patients infected with Plasmodium vivax. Panning
      on recombinant PvRII enriched a population of scFvs that recognized region II of
      the P. vivax Duffy binding protein (DBP). Three clones of scFvs that reacted with
      PvRII were selected, and their biological functions were analyzed. These scFvs
      inhibited erythrocyte binding to DBP. Clone SFDBII92 had the greatest affinity
      (dissociation constant = 3.62 x 10(-8) M) and the greatest inhibition activity
      (50% inhibitory concentration approximately 2.9 microg/ml) to DBP. Thus, we
      demonstrated that human neutralizing antibody could be made from malaria patients
      using phage display and that these neutralizing scFvs should prove valuable for
      developing both passive and active immunization strategies based on DBP.

PMID- 17460119
TI  - Evaluation of the LIAISON chemiluminescence immunoassay for diagnosis of
      syphilis.
AB  - We report the results of an evaluation of the LIAISON Treponema pallidum-specific
      assay, a one-step sandwich chemiluminescence immunoassay (CLIA), as a screening
      test and as a confirmatory test for the diagnosis of syphilis. The assay was
      compared with the CAPTIA Syphilis-G enzyme immunoassay (EIA) and with a testing
      algorithm that also included the rapid plasma reagin (RPR) and T. pallidum
      particle agglutination (PA) assays. As a screening test, the CLIA showed levels
      of agreement with the EIA and with the algorithm, respectively, of 94.1 and 100%
      for 51 samples from patients with primary or secondary syphilis, 93.2 and 98.7%
      for 999 samples sent to the laboratory for routine syphilis testing, 84.5 and
      94.0% for 200 samples from human immunodeficiency virus-positive patients, 98.0
      and 100% for 200 samples from pregnant patients, and 94.3 and 98.3% for 992
      samples from apparently healthy adults. As a confirmatory test, the CLIA showed
      99% agreement with the EIA for 204 RPR-positive samples. After resolution with
      further T. pallidum PA testing and the discarding of one sample of insufficient
      quantity, there was 100% agreement for the remaining 203 samples. For the total
      group of 2,645 samples, the overall relative sensitivity was 95.8% and the
      relative specificity was 99.1%. We conclude that the LIAISON CLIA demonstrated
      excellent sensitivity and specificity when evaluated as a confirmatory test and
      as a screening test for syphilis among various patient populations, including
      specific populations with reportedly increased rates of false-positive
      nontreponemal test results.

PMID- 17460120
TI  - Protein arms in the kinetochore-microtubule interface of the yeast DASH complex.
AB  - The yeast DASH complex is a heterodecameric component of the kinetochore
      necessary for accurate chromosome segregation. DASH forms closed rings around
      microtubules with a large gap between the DASH ring and the microtubule cylinder.
      We characterized the microtubule-binding properties of limited proteolysis
      products and subcomplexes of DASH, thus identifying candidate polypeptide
      extensions involved in establishing the DASH-microtubule interface. The acidic C
      terminal extensions of tubulin subunits are not essential for DASH binding. We
      also measured the molecular mass of DASH rings on microtubules with scanning
      transmission electron microscopy and found that approximately 25 DASH
      heterodecamers assemble to form each ring. Dynamic association and relocation of
      multiple flexible appendages of DASH may allow the kinetochore to translate along
      the microtubule surface.

PMID- 17460121
TI  - Sequential and distinct roles of the cadherin domain-containing protein Axl2p in
      cell polarization in yeast cell cycle.
AB  - Polarization of cell growth along a defined axis is essential for the generation
      of cell and tissue polarity. In the budding yeast Saccharomyces cerevisiae, Axl2p
      plays an essential role in polarity-axis determination, or more specifically,
      axial budding in MATa or alpha cells. Axl2p is a type I membrane glycoprotein
      containing four cadherin-like motifs in its extracellular domain. However, it is
      not known when and how Axl2p functions together with other components of the
      axial landmark, such as Bud3p and Bud4p, to direct axial budding. Here, we show
      that the recruitment of Axl2p to the bud neck after S/G2 phase of the cell cycle
      depends on Bud3p and Bud4p. This recruitment is mediated via an interaction
      between Bud4p and the central region of the Axl2p cytoplasmic tail. This region
      of Axl2p, together with its N-terminal region and its transmembrane domain, is
      sufficient for axial budding. In addition, our work demonstrates a previously
      unappreciated role for Axl2p. Axl2p interacts with Cdc42p and other polarity
      establishment proteins, and it regulates septin organization in late G1
      independently of its role in polarity-axis determination. Together, these results
      suggest that Axl2p plays sequential and distinct roles in the regulation of
      cellular morphogenesis in yeast cell cycle.

PMID- 17460122
TI  - Patient-care questions that physicians are unable to answer.
AB  - OBJECTIVE: To describe the characteristics of unanswered clinical questions and
      propose interventions that could improve the chance of finding answers. DESIGN:
      In a previous study, investigators observed primary care physicians in their
      offices and recorded questions that arose during patient care. Questions that
      were pursued by the physician, but remained unanswered, were grouped into generic
      types. In the present study, investigators attempted to answer these questions
      and developed recommendations aimed at improving the success rate of finding
      answers. MEASUREMENTS: Frequency of unanswered question types and recommendations
      to increase the chance of finding answers. RESULTS: In an earlier study, 48
      physicians asked 1062 questions during 192 half-day office observations.
      Physicians could not find answers to 237 (41%) of the 585 questions they pursued.
      The present study grouped the unanswered questions into 19 generic types. Three
      types accounted for 128 (54%) of the unanswered questions: (1) "Undiagnosed
      finding" questions asked about the management of abnormal clinical findings, such
      as symptoms, signs, and test results (What is the approach to finding X?); (2)
      "Conditional" questions contained qualifying conditions that were appended to
      otherwise simple questions (What is the management of X, given Y? where "given Y"
      is the qualifying condition that makes the question difficult.); and (3)
      "Compound" questions asked about the association between two highly specific
      elements (Can X cause Y?). The study identified strategies to improve clinical
      information retrieval, listed below. CONCLUSION: To improve the chance of finding
      answers, physicians should change their search strategies by rephrasing their
      questions and searching more clinically oriented resources. Authors of clinical
      information resources should anticipate questions that may arise in practice, and
      clinical information systems should provide clearer and more explicit answers.

PMID- 17460123
TI  - Development and psychometric evaluation of the Impact of Health Information
      Technology (I-HIT) scale.
AB  - OBJECTIVE: The use of health information technology (HIT) for the support of
      communication processes and data and information access in acute care settings is
      a relatively new phenomenon. A means of evaluating the impact of HIT in hospital
      settings is needed. The purpose of this research was to design and
      psychometrically evaluate the Impact of Health Information Technology scale (I
      HIT). I-HIT was designed to measure the perception of nurses regarding the ways
      in which HIT influences interdisciplinary communication and workflow patterns and
      nurses' satisfaction with HIT applications and tools. DESIGN: Content for a 43
      item tool was derived from the literature, and supported theoretically by the
      Coiera model and by nurse informaticists. Internal consistency reliability
      analysis using Cronbach's alpha was conducted on the 43-item scale to initiate
      the item reduction process. Items with an item total correlation of less than
      0.35 were removed, leaving a total of 29 items. MEASUREMENTS: Item analysis,
      exploratory principal component analysis and internal consistency reliability
      using Cronbach's alpha were used to confirm the 29-item scale. RESULTS: Principal
      components analysis with Varimax rotation produced a four-factor solution that
      explained 58.5% of total variance (general advantages, information tools to
      support information needs, information tools to support communication needs, and
      workflow implications). Internal consistency of the total scale was 0.95 and
      ranged from 0.80-0.89 for four subscales. CONCLUSION: I-HIT demonstrated
      psychometric adequacy and is recommended to measure the impact of HIT on nursing
      practice in acute care settings.

PMID- 17460124
TI  - Semantic classification of biomedical concepts using distributional similarity.
AB  - OBJECTIVE: To develop an automated, high-throughput, and reproducible method for
      reclassifying and validating ontological concepts for natural language processing
      applications. DESIGN: We developed a distributional similarity approach to
      classify the Unified Medical Language System (UMLS) concepts. Classification
      models were built for seven broad biomedically relevant semantic classes created
      by grouping subsets of the UMLS semantic types. We used contextual features based
      on syntactic properties obtained from two different large corpora and used alpha
      skew divergence as the similarity measure. MEASUREMENTS: The testing sets were
      automatically generated based on the changes by the National Library of Medicine
      to the semantic classification of concepts from the UMLS 2005AA to the 2006AA
      release. Error rates were calculated and a misclassification analysis was
      performed. RESULTS: The estimated lowest error rates were 0.198 and 0.116 when
      considering the correct classification to be covered by our top prediction and
      top 2 predictions, respectively. CONCLUSION: The results demonstrated that the
      distributional similarity approach can recommend high level semantic
      classification suitable for use in natural language processing.

PMID- 17460125
TI  - A code of professional ethical conduct for the American Medical Informatics
      Association: an AMIA Board of Directors approved white paper.
AB  - The AMIA Board of Directors has decided to periodically publish AMIA's Code of
      Professional Ethical Conduct for its members in the Journal of the American
      Medical Informatics Association. The Code also will be available on the AMIA Web
      site at www.amia.org as it continues to evolve in response to feedback from the
      AMIA membership. The AMIA Board acknowledges the continuing work and dedication
      of the AMIA Ethics Committee. AMIA is the copyright holder of this work.

PMID- 17460126
TI  - Randomized trial to improve prescribing safety during pregnancy.
AB  - OBJECTIVE: This study sought to determine whether a computerized tool that
      alerted pharmacists when pregnant patients were prescribed U.S. Food and Drug
      Administration pregnancy risk category D or X medications was effective in
      decreasing dispensings of these medications. DESIGN: Randomized trial. Pharmacy,
      diagnostic, and laboratory data were linked to identify pregnant patients
      prescribed targeted medications. Women (n = 11,100) were randomized to
      intervention or usual care. Physicians and pharmacists collaborated on the
      intervention. MEASUREMENTS: The primary outcome was the proportion of pregnant
      women dispensed a category D or X medication. The secondary outcome was the total
      number of first dispensings of targeted medications. RESULTS: A total of 2.9% of
      intervention (n = 177) and 5.5% of usual care (n = 276) patients were dispensed
      targeted medications (p < 0.001): 1.8% of intervention (n = 108) and 3.9% of
      usual care (n = 198) patients were dispensed only category D medication(s); 0.9%
      of intervention (n = 54) and 1.2% of usual care (n = 58) patients were dispensed
      only category X medication(s); 0.2% of intervention (n = 15) and 0.4% of usual
      care (n = 20) patients were dispensed both category D and X medications (p =
      0.05). This resulted in intervention patients receiving 238 dispensings of unique
      targeted medications and usual care patients receiving 361 dispensings of unique
      targeted medications (p = 0.03). The study was stopped primarily due to 2 false
      positive alert types: Misidentification of medications as contraindicated in
      pregnancy by the pharmacy information system and misidentification of pregnancy
      related to delayed transfer of diagnosis information. CONCLUSION: Coupling data
      from information systems with knowledge and skills of physicians and pharmacists
      resulted in improved prescribing safety. Systems limitations contributed to
      project discontinuation. Linking ambulatory clinical, laboratory, and pharmacy
      information to provide safety alerts is not sufficient to ensure project success
      and sustainability.

PMID- 17460127
TI  - The extent and importance of unintended consequences related to computerized
      provider order entry.
AB  - BACKGROUND: Computerized provider order entry (CPOE) systems can help hospitals
      improve health care quality, but they can also introduce new problems. The extent
      to which hospitals experience unintended consequences of CPOE, which include more
      than errors, has not been quantified in prior research. OBJECTIVE: To discover
      the extent and importance of unintended adverse consequences related to CPOE
      implementation in U.S. hospitals. DESIGN, SETTING, AND PARTICIPANTS: Building on
      a prior qualitative study involving fieldwork at five hospitals, we developed and
      then administered a telephone survey concerning the extent and importance of CPOE
      related unintended adverse consequences to representatives from 176 hospitals in
      the U.S. that have CPOE. MEASUREMENTS: Self report by key informants of the
      extent and level of importance to the overall function of the hospital of eight
      types of unintended adverse consequences experienced by sites with inpatient
      CPOE. RESULTS We found that hospitals experienced all eight types of unintended
      adverse consequences, although respondents identified several they considered
      more important than others. Those related to new work/more work, workflow, system
      demands, communication, emotions, and dependence on the technology were ranked as
      most severe, with at least 72% of respondents ranking them as moderately to very
      important. Hospital representatives are less sure about shifts in the power
      structure and CPOE as a new source of errors. There is no relation between kinds
      of unintended consequences and number of years CPOE has been used. Despite the
      relatively short length of time most hospitals have had CPOE (median five years),
      it is highly infused, or embedded, within work practice at most of these sites.
      CONCLUSIONS: The unintended consequences of CPOE are widespread and important to
      those knowledgeable about CPOE in hospitals. They can be positive, negative, or
      both, depending on one's perspective, and they continue to exist over the
      duration of use. Aggressive detection and management of adverse unintended
      consequences is vital for CPOE success.

PMID- 17460128
TI  - Variation of SNOMED CT coding of clinical research concepts among coding experts.
AB  - OBJECTIVE: To compare consistency of coding among professional SNOMED CT coders
      representing three commercial providers of coding services when coding clinical
      research concepts with SNOMED CT. DESIGN: A sample of clinical research questions
      from case report forms (CRFs) generated by the NIH-funded Rare Disease Clinical
      Research Network (RDCRN) were sent to three coding companies with instructions to
      code the core concepts using SNOMED CT. The sample consisted of 319
      question/answer pairs from 15 separate studies. The companies were asked to
      select SNOMED CT concepts (in any form, including post-coordinated) that capture
      the core concept(s) reflected in the question. Also, they were asked to state
      their level of certainty, as well as how precise they felt their coding was.
      MEASUREMENTS: Basic frequencies were calculated to determine raw level agreement
      among the companies and other descriptive information. Krippendorff's alpha was
      used to determine a statistical measure of agreement among the coding companies
      for several measures (semantic, certainty, and precision). RESULTS: No
      significant level of agreement among the experts was found. CONCLUSION: There is
      little semantic agreement in coding of clinical research data items across coders
      from 3 professional coding services, even using a very liberal definition of
      agreement.

PMID- 17460129
TI  - A self-scaling, distributed information architecture for public health, research,
      and clinical care.
AB  - OBJECTIVE: This study sought to define a scalable architecture to support the
      National Health Information Network (NHIN). This architecture must concurrently
      support a wide range of public health, research, and clinical care activities.
      STUDY DESIGN: The architecture fulfils five desiderata: (1) adopt a distributed
      approach to data storage to protect privacy, (2) enable strong institutional
      autonomy to engender participation, (3) provide oversight and transparency to
      ensure patient trust, (4) allow variable levels of access according to
      investigator needs and institutional policies, (5) define a self-scaling
      architecture that encourages voluntary regional collaborations that coalesce to
      form a nationwide network. RESULTS: Our model has been validated by a large
      scale, multi-institution study involving seven medical centers for cancer
      research. It is the basis of one of four open architectures developed under
      funding from the Office of the National Coordinator of Health Information
      Technology, fulfilling the biosurveillance use case defined by the American
      Health Information Community. The model supports broad applicability for regional
      and national clinical information exchanges. CONCLUSIONS: This model shows the
      feasibility of an architecture wherein the requirements of care providers,
      investigators, and public health authorities are served by a distributed model
      that grants autonomy, protects privacy, and promotes participation.

PMID- 17460131
TI  - A description and functional taxonomy of rule-based decision support content at a
      large integrated delivery network.
AB  - OBJECTIVE: This study sought to develop a functional taxonomy of rule-based
      clinical decision support. DESIGN: The rule-based clinical decision support
      content of a large integrated delivery network with a long history of computer
      based point-of-care decision support was reviewed and analyzed along four
      functional dimensions: trigger, input data elements, interventions, and offered
      choices. RESULTS: A total of 181 rule types were reviewed, comprising 7,120
      different instances of rule usage. A total of 42 taxa were identified across the
      four categories. Many rules fell into multiple taxa in a given category. Entered
      order and stored laboratory result were the most common triggers; laboratory
      result, drug list, and hospital unit were the most frequent data elements used.
      Notify and log were the most common interventions, and write order, defer
      warning, and override rule were the most common offered choices. CONCLUSION: A
      relatively small number of taxa successfully described a large body of clinical
      knowledge. These taxa can be directly mapped to functions of clinical systems and
      decision support systems, providing feature guidance for developers,
      implementers, and certifiers of clinical information systems.

PMID- 17460132
TI  - Encryption characteristics of two USB-based personal health record devices.
AB  - Personal health records (PHRs) hold great promise for empowering patients and
      increasing the accuracy and completeness of health information. We reviewed two
      small USB-based PHR devices that allow a patient to easily store and transport
      their personal health information. Both devices offer password protection and
      encryption features. Analysis of the devices shows that they store their data in
      a Microsoft Access database. Due to a flaw in the encryption of this database,
      recovering the user's password can be accomplished with minimal effort. Our
      analysis also showed that, rather than encrypting health information with the
      password chosen by the user, the devices stored the user's password as a string
      in the database and then encrypted that database with a common password set by
      the manufacturer. This is another serious vulnerability. This article describes
      the weaknesses we discovered, outlines three critical flaws with the security
      model used by the devices, and recommends four guidelines for improving the
      security of similar devices.

PMID- 17460130
TI  - A systematic review of the performance characteristics of clinical event monitor
      signals used to detect adverse drug events in the hospital setting.
AB  - OBJECTIVE: Despite demonstrated benefits, few healthcare organizations have
      implemented clinical event monitors to detect adverse drug events (ADEs). The
      objective of this study was to conduct a systematic review of pharmacy and
      laboratory signals used by clinical event monitors to detect ADEs in hospitalized
      adults. DESIGN: We performed a comprehensive search of MEDLINE, CINHAL and EMBASE
      to identify studies published between 1985 through 2006. Studies were included if
      they: described a clinical event monitor to detect ADEs in an adult hospital
      setting; described laboratory or pharmacy ADE signals; and, provided positive
      predictive values (PPVs) or information to allow the calculation of PPVs for
      individual ADE signals. MEASUREMENTS: We calculated overall estimates of PPVs and
      95% confidence intervals (CIs) for signals reported in 2 or more studies and
      contained no evidence heterogeneity. Results were examined by signal category:
      medication levels, laboratory tests, or antidotes. RESULTS: We identified 12
      observational studies describing 36 unique ADE signals. Fifteen signals (3
      antidotes, 4 medication levels, and 8 laboratory values) contained no evidence of
      heterogeneity. The pooled PPVs for these individual signals ranged from 0.03
      [CI=0.03-0.03] for hypokalemia, to 0.50 [CI=0.39-0.61] for supratherapeutic
      quinidine level. In general, antidotes (range=0.09-0.11) had the lowest PPVs,
      followed by laboratory values (0.03-0.27), and medication levels (0.03-0.50).
      CONCLUSION: Results from this study should help clinical information system and
      computerized decision support producers develop or improve existing clinical
      event monitors to detect ADEs in their own hospitals by prioritizing those
      signals with the highest PPVs [corrected]

PMID- 17460133
TI  - A qualitative investigation of the content of dental paper-based and computer
      based patient record formats.
AB  - OBJECTIVE: Approximately 25% of all general dentists practicing in the United
      States use a computer in the dental operatory. Only 1.8% maintain completely
      electronic records. Anecdotal evidence suggests that dental computer-based
      patient records (CPR) do not represent clinical information with the same degree
      of completeness and fidelity as paper records. The objective of this study was to
      develop a basic content model for clinical information in paper-based records and
      examine its degree of coverage by CPRs. DESIGN: We compiled a baseline dental
      record (BDR) from a purposive sample of 10 paper record formats (two from dental
      schools and four each from dental practices and commercial sources). We extracted
      all clinical data fields, removed duplicates, and organized the resulting
      collection in categories/subcategories. We then mapped the fields in four market
      leading dental CPRs to the BDR. MEASUREMENTS: We calculated frequency counts of
      BDR categories and data fields for all paper-based and computer-based record
      formats, and cross-mapped information coverage at both the category and the data
      field level. RESULTS: The BDR had 20 categories and 363 data fields. On average,
      paper records and CPRs contained 14 categories, and 210 and 174 fields,
      respectively. Only 72, or 20%, of the BDR fields occurred in five or more paper
      records. Categories related to diagnosis were missing from most paper-based and
      computer-based record formats. The CPRs rarely used the category names and
      groupings of data fields common in paper formats. CONCLUSION: Existing paper
      records exhibit limited agreement on what information dental records should
      contain. The CPRs only cover this information partially, and may thus impede the
      adoption of electronic patient records.

PMID- 17460134
TI  - The utility of adding retrospective medication profiling to computerized provider
      order entry in an ambulatory care population.
AB  - BACKGROUND: We assessed whether medication safety improved when a medication
      profiling program was added to a computerized provider order entry system.
      DESIGN: Between June 2001 and January 2002 we profiled outpatients with potential
      prescribing errors using computerized retrospective drug utilization software. We
      focused primarily on drug interactions. Patients were randomly assigned either to
      Provider Feedback or to Usual Care. Subsequent adverse drug event (ADE) incidence
      and other outcomes, including ADE preventability and severity, occurring up to 1
      year following the last profiling date were evaluated retrospectively by a
      pharmacist blinded to patient assignment. MEASUREMENTS: Data were abstracted
      using a study-designed instrument. An ADE was defined by an Adverse Drug Reaction
      Probability scale score of 1 or more. Statistical analyses included negative
      binomial regression for comparing ADE incidence. RESULTS: Of 913 patients in the
      analytic sample, 371 patients (41%) had one or more ADEs. Incidence, by
      individual, was not significantly different between Usual Care and Provider
      Feedback groups (37% vs. 45%; p = 0.06; Coefficient, 0.19; 95% CI: -0.008,
      0.390). ADE severity was also similar. For example, 51% of ADEs in the Usual Care
      and 58% in the Provider Feedback groups involved symptoms that were not serious
      (95% CI for the difference, -15%, 2%). Finally, ADE preventability did not
      differ. For example, 16% in the Usual Care group and 17% in the Provider Feedback
      group had an associated warning (95% CI for the difference, -7 to 5%; p = 0.79).
      CONCLUSION: Medications safety did not improve with the addition of a medication
      profiling program to an electronic prescribing system.

PMID- 17460135
TI  - Communication outcomes of critical imaging results in a computerized notification
      system.
AB  - OBJECTIVE: Communication of abnormal test results in the outpatient setting is
      prone to error. Using information technology can improve communication and
      improve patient safety. We standardized processes and procedures in a
      computerized test result notification system and examined their effectiveness to
      reduce errors in communication of abnormal imaging results. DESIGN: We
      prospectively analyzed outcomes of computerized notification of abnormal test
      results (alerts) that providers did not explicitly acknowledge receiving in the
      electronic medical record of an ambulatory multispecialty clinic. MEASUREMENTS:
      In the study period, 190,799 outpatient visits occurred and 20,680 outpatient
      imaging tests were performed. We tracked 1,017 transmitted alerts electronically.
      Using a taxonomy of communication errors, we focused on alerts in which errors in
      acknowledgment and reception occurred. Unacknowledged alerts were identified
      through electronic tracking. Among these, we performed chart reviews to determine
      any evidence of documented response, such as ordering a follow-up test or
      consultation. If no response was documented, we contacted providers by telephone
      to determine their awareness of the test results and any follow-up action they
      had taken. These processes confirmed the presence or absence of alert reception.
      RESULTS: Providers failed to acknowledge receipt of over one-third (368 of 1,017)
      of transmitted alerts. In 45 of these cases (4% of abnormal results), the imaging
      study was completely lost to follow-up 4 weeks after the date of study. Overall,
      0.2% of outpatient imaging was lost to follow-up. The rate of lost to follow-up
      imaging was 0.02% per outpatient visit. CONCLUSION: Imaging results continue to
      be lost to follow-up in a computerized test result notification system that
      alerted physicians through the electronic medical record. Although comparison
      data from previous studies are limited, the rate of results lost to follow-up
      appears to be lower than that reported in systems that do not use information
      technology comparable to what we evaluated.

PMID- 17460136
TI  - Adoption of order entry with decision support for chronic care by physician
      organizations.
AB  - OBJECTIVE: This study sought to explore physician organizations' adoption of
      chronic care guidelines in order entry systems and to investigate the
      organizational and market-related factors associated with this adoption. DESIGN:
      A quantitative nationwide survey of all primary care medical groups in the United
      States with 20 or more physicians; data were collected on 1,104 physician
      organizations, representing a 70% response rate. MEASUREMENTS: Measurements were
      the presence of an asthma, diabetes, or congestive heart failure guideline in a
      physician organization's order entry system; size; age of the organization;
      number of clinic locations; type of ownership; health maintenance organization
      market penetration; urban/rural location; and presence of external incentives to
      improve quality of care. RESULTS: Only 27% of organizations reported access to
      order entry with decision support for chronic disease care. External incentives
      for quality is the only factor significantly associated with adoption of these
      tools. Organizations experiencing greater external incentives for quality are
      more likely to adopt order entry with decision support. CONCLUSION: Because
      external incentives are strong drivers of adoption, policies requiring reporting
      of chronic care measurements and rewarding improvement as well as financial
      incentives for use of specific information technology tools are likely to
      accelerate adoption of order entry with decision support.

PMID- 17460137
TI  - Evaluation of outpatient computerized physician medication order entry systems: a
      systematic review.
AB  - This paper provides a systematic literature review of CPOE evaluation studies in
      the outpatient setting on: safety; cost and efficiency; adherence to guideline;
      alerts; time; and satisfaction, usage, and usability. Thirty articles with
      original data (randomized clinical trial, non-randomized clinical trial, or
      observational study designs) met the inclusion criteria. Only four studies
      assessed the effect of CPOE on safety. The effect was not significant on the
      number of adverse drug events. Only one study showed a significant reduction of
      the number of medication errors. Three studies showed significant reductions in
      medication costs; five other studies could not support this. Most studies on
      adherence to guidelines showed a significant positive effect. The relatively
      small number of evaluation studies published to date do not provide adequate
      evidence that CPOE systems enhance safety and reduce cost in the outpatient
      settings. There is however evidence for (a) increasing adherence to guidelines,
      (b) increasing total prescribing time, and (c) high frequency of ignored alerts.

PMID- 17460138
TI  - A data accounting system for clinical investigators.
AB  - Clinical investigators often preprocess, process, and analyze their data without
      benefit of formally organized research centers to oversee data management. This
      article outlines a practical three-file structure to help guide these
      investigators track and document their data through processing and analyses. The
      proposed process can be implemented without additional training or specialized
      software. Thus, it is particularly well suited for research projects with small
      budgets or limited access to viable research/data coordinating centers.

PMID- 17460139
TI  - Issues in biomedical research data management and analysis: needs and barriers.
AB  - OBJECTIVES: A. Identify the current state of data management needs of academic
      biomedical researchers. B. Explore their anticipated data management and analysis
      needs. C. Identify barriers to addressing those needs. DESIGN: A multimodal needs
      analysis was conducted using a combination of an online survey and in-depth one
      on-one semi-structured interviews. Subjects were recruited via an e-mail list
      representing a wide range of academic biomedical researchers in the Pacific
      Northwest. MEASUREMENTS: The results from 286 survey respondents were used to
      provide triangulation of the qualitative analysis of data gathered from 15 semi
      structured in-depth interviews. RESULTS: Three major themes were identified: 1)
      there continues to be widespread use of basic general-purpose applications for
      core data management; 2) there is broad perceived need for additional support in
      managing and analyzing large datasets; and 3) the barriers to acquiring currently
      available tools are most commonly related to financial burdens on small labs and
      unmet expectations of institutional support. CONCLUSION: Themes identified in
      this study suggest that at least some common data management needs will best be
      served by improving access to basic level tools such that researchers can solve
      their own problems. Additionally, institutions and informaticians should focus on
      three components: 1) facilitate and encourage the use of modern data exchange
      models and standards, enabling researchers to leverage a common layer of
      interoperability and analysis; 2) improve the ability of researchers to maintain
      provenance of data and models as they evolve over time though tools and the
      leveraging of standards; and 3) develop and support information management
      service cores that could assist in these previous components while providing
      researchers with unique data analysis and information design support within a
      spectrum of informatics capabilities.

PMID- 17460140
TI  - Mesenchymal stem cells prevent progressive experimental renal failure but
      maldifferentiate into glomerular adipocytes.
AB  - Glomerulonephritis (GN) is a major cause of renal failure. This study sought to
      determine whether intrarenal injection of rat mesenchymal stem cells (MSC) can
      preserve renal function in a progressive rat model of GN. Early in GN (day 10),
      fluorescently labeled rat MSC localized to more than 70% of glomeruli,
      ameliorated acute renal failure, and reduced glomerular adhesions. Fifty days
      later, proteinuria had progressed in controls to 40 +/- 25 mg/d but stayed low in
      MSC-treated rats (13 +/- 4 mg/d; P < 0.01). Renal function on day 60 in the MSC
      group was better than in medium controls. Kidneys of the MSC group as compared
      with controls on day 60 contained 11% more glomeruli per 1-mm(2) section of
      cortex but also significantly more collagen types I, III, and IV and alpha-smooth
      muscle actin. Approximately 20% of the glomeruli of MSC-treated rats contained
      single or clusters of large adipocytes with pronounced surrounding fibrosis.
      Adipocytes exhibited fluorescence in their cytoplasm and/or intracellular lipid
      droplets. Lipid composition in these adipocytes in vivo mirrored that of MSC that
      underwent adipogenic differentiation in vitro. Thus, in this GN model, the early
      beneficial effect of MSC of preserving damaged glomeruli and maintaining renal
      function was offset by a long-term partial maldifferentiation of intraglomerular
      MSC into adipocytes accompanied by glomerular sclerosis. These data suggest that
      MSC treatment can be a valuable therapeutic approach only if adipogenic
      maldifferentiation is prevented.

PMID- 17460141
TI  - Abrogation of protein uptake through megalin-deficient proximal tubules does not
      safeguard against tubulointerstitial injury.
AB  - Sustained proteinuria and tubulointerstitial damage have been closely linked with
      progressive renal failure. Upon excess protein endocytosis, tubular epithelial
      cells are thought to produce mediators that promote inflammation, tubular
      degeneration, and fibrosis. This concept was tested in a transgenic mouse model
      with megalin deficiency. Application of an anti-glomerular basement membrane
      serum to transgenic megalin-deficient mice [Cre(+)/GN] and megalin-positive
      littermates [Cre(-)/GN] produced the typical glomerulonephritis (GN) with heavy
      proteinuria in both groups. Tubulointerstitial damages correlated closely with
      glomerular damages in pooled Cre(+)/GN and Cre(-)/GN mice. Owing to a mosaic
      pattern of megalin expression in the mutant mice, Cre(+)/GN kidneys permitted
      side-by-side analysis of megalin-deficient and megalin-positive tubules in the
      same kidney. Protein endocytosis was found only in megalin-positive cells. TGF
      beta, intercellular adhesion molecule, vascular cellular adhesion molecule,
      endothelin-1, and cell proliferation were high in megalin-positive cells, whereas
      apoptosis, heat-shock protein 25, and osteopontin were enhanced in megalin
      deficient cells. No fibrotic changes were associated with either phenotype.
      Tubular degeneration with interstitial inflammation was found only in nephrons
      with extensive crescentic lesions at the glomerulotubular junction. In sum,
      enhanced protein endocytosis indeed led to an upregulation of profibrotic
      mediators in a megalin-dependent way; however, there was no evidence that
      endocytosis played a pathogenetic role in the development of the
      tubulointerstitial disease.

PMID- 17460142
TI  - Comprehensive mutation screening in 55 probands with type 1 primary hyperoxaluria
      shows feasibility of a gene-based diagnosis.
AB  - Mutations in AGXT, a locus mapped to 2q37.3, cause deficiency of liver-specific
      alanine:glyoxylate aminotransferase (AGT), the metabolic error in type 1 primary
      hyperoxaluria (PH1). Genetic analysis of 55 unrelated probands with PH1 from the
      Mayo Clinic Hyperoxaluria Center, to date the largest with availability of
      complete sequencing across the entire AGXT coding region and documented hepatic
      AGT deficiency, suggests that a molecular diagnosis (identification of two
      disease alleles) is feasible in 96% of patients. Unique to this PH1 population
      was the higher frequency of G170R, the most common AGXT mutation, accounting for
      37% of alleles, and detection of a new 3' end deletion (Ex 11_3'UTR del). A
      described frameshift mutation (c.33_34insC) occurred with the next highest
      frequency (11%), followed by F152I and G156R (frequencies of 6.3 and 4.5%,
      respectively), both surpassing the frequency (2.7%) of I244T, the previously
      reported third most common pathogenic change. These sequencing data indicate that
      AGXT is even more variable than formerly believed, with 28 new variants (21
      mutations and seven polymorphisms) detected, with highest frequencies on exons 1,
      4, and 7. When limited to these three exons, molecular analysis sensitivity was
      77%, compared with 98% for whole-gene sequencing. These are the first data in
      support of comprehensive AGXT analysis for the diagnosis of PH1, obviating a
      liver biopsy in most well-characterized patients. Also reported here is
      previously unavailable evidence for the pathogenic basis of all AGXT missense
      variants, including evolutionary conservation data in a multisequence alignment
      and use of a normal control population.

PMID- 17460143
TI  - Estimated glomerular filtration rate and urinary albumin excretion are
      independently associated with greater arterial stiffness: the Hoorn Study.
AB  - Mild renal insufficiency is a risk factor for cardiovascular disease (CVD). Both
      a decline in GFR and (micro)albuminuria are associated with greater
      cardiovascular mortality. In ESRD, arterial stiffness, an important cause of CVD,
      is known to be greater, but few data exist in individuals with mild renal
      insufficiency or microalbuminuria. This study investigated the association of
      impaired renal function expressed as lower GFR or greater urinary albumin
      excretion with arterial stiffness. In a population-based study in 806 individuals
      (402 men), mean age 68 yr (range 50 to 87), peripheral arterial stiffness (by
      compliance and distensibility of the carotid, brachial, and femoral arteries and
      by the carotid elastic modulus [E(inc)]) and central arterial stiffness (by total
      systemic arterial compliance, carotid-femoral transit time, and aortic
      augmentation index) were measured ultrasonically. GFR was estimated (eGFR) by the
      Modification of Diet in Renal Disease (MDRD) formula. Urinary albumin excretion
      was expressed as urinary albumin/creatinine ratio (UACR). eGFR was 60.6 +/- 11.1
      ml/min per 1.73 m(2). Median UACR was 0.57 mg/mmol (range 0.1 to 26.6). After
      adjustment for age, mean arterial pressure (MAP), gender, and glucose tolerance
      status (GTS), each 5-ml/min per 1.73 m(2) lower eGFR was associated with a lower
      distensibility coefficient of the carotid (regression coefficient beta -0.20 10(
      3)/kPa; 95% confidence interval [CI] -0.34 to -0.07 10(-3)/kPa) and brachial
      artery (-0.15 10(-3)/kPa; 95% CI -0.28 to -0.03 10(-3)/kPa) and a greater carotid
      E(inc) (0.02 kPa; 95% CI 0.0004 to 0.04 kPa). No statistically significant
      association was found of eGFR with other arterial stiffness indices. After
      adjustment for age, MAP, gender, and GTS, a greater UACR (per quartile) was
      associated with a greater E(inc) (0.03 kPa; 95% CI 0.001 to 0.07 kPa) and a trend
      to a lower distensibility coefficient (-0.24 10(-3)/kPa; 95% CI -0.49 to 0.02 10(
      3)/kPa) of the carotid artery. After adjustment for age, MAP, gender, and GTS, a
      greater UACR (per quartile) was in addition associated with a shorter carotid
      femoral transit time (-1.67 ms; 95% CI -3.24 to -0.10 ms). These associations
      were not substantially changed by mutual adjustment for eGFR and UACR. In
      individuals with mild renal insufficiency, both a lower eGFR and a greater
      albumin excretion, even below levels that are considered to reflect
      microalbuminuria, are independently associated with greater arterial stiffness.
      Moreover, these associations were mutually independent. These findings may
      explain, in part, why eGFR and microalbuminuria are associated with greater risk
      for CVD and suggest that amelioration of arterial stiffness could be a target of
      intervention.

PMID- 17460144
TI  - Inhibition of Toll-like receptor-7 (TLR-7) or TLR-7 plus TLR-9 attenuates
      glomerulonephritis and lung injury in experimental lupus.
AB  - Small nuclear RNA and associated lupus autoantigens activate B cells and
      dendritic cells via Toll-like receptor-7 (TLR-7); therefore, TLR-7 may represent
      a potential therapeutic target in lupus. MRL lpr mice were administered an
      injection of either saline or synthetic oligodeoxynucleotides with
      immunoregulatory sequences (IRS) that specifically block signaling via TLR-7 (IRS
      661) or via TLR-7 and TLR-9 (IRS 954, which uses a active sequence from IRS 661
      along with a TLR-9 inhibitory sequence) from weeks 11 to 24 of age. IRS 661 and
      IRS 954 both significantly reduced the weight of spleen and lymph nodes as well
      as serum levels of TNF as compared with saline-treated MRL lpr mice. Only IRS 661
      but not IRS 954 significantly reduced serum levels of IL-12p40, anti-dsDNA
      IgG(2a), IgG(2b), and anti-Smith IgG. Both IRS localized to the kidney after
      intraperitoneal injection and significantly improved the activity index and
      chronicity index for lupus nephritis in MRL lpr mice. This was associated with
      significant reduction of renal glomerular and interstitial macrophage infiltrates
      and the number of interstitial T cells. Autoimmune lung injury was also
      attenuated with IRS 661 and IRS 954. These data demonstrate that TLR-7
      antagonism, initiated after the onset of autoimmunity, can prevent autoimmune
      kidney and lung injury in MRL lpr mice. Concomitant blockade of TLR-9 with IRS
      954 neutralized the effect of TLR-7 blockade on dsDNA IgG(2a), dsDNA IgG(2b), and
      Smith antigen autoantibodies but had neither additive nor opposing effects on
      autoimmune lung and kidney injury. Hence, TLR-7 is proposed as a novel and
      potential therapeutic target in systemic lupus erythematosus.

PMID- 17460145
TI  - Mycophenolate mofetil versus azathioprine for prevention of chronic allograft
      dysfunction in renal transplantation: the MYSS follow-up randomized, controlled
      clinical trial.
AB  - The Mycophenolate Steroids Sparing (MYSS) study found that in renal transplant
      recipients who were on immunosuppressive therapy with the cyclosporine
      microemulsion Neoral, mycophenolate mofetil (MMF) was not better than
      azathioprine in preventing acute rejection at 21 mo after transplantation and was
      15 times more expensive. The MYSS Follow-up Study, an extension of MYSS, was
      aimed at comparing long-term outcome of 248 MYSS patients according to their
      original randomization to MMF (1 g twice daily) or azathioprine (75 to 100 mg/d).
      Primary outcome was estimated GFR at 5 yr after transplantation. Mean 5-yr GFR
      difference between azathioprine and mycophenolate was 4.67 ml/min per 1.73 m(2)
      (95% confidence interval [CI] -0.43 to 9.77 ml/min per 1.73 m(2); P = 0.07). GFR
      from month 6 (mean +/- SEM: 54.3 +/- 1.6 versus 53.9 +/- 1.5 ml/min per 1.73
      m(2); P = 0.83) to month 72 after transplantation (49.5 +/- 2.2 versus 47.3 +/-
      2.4 ml/min per 1.73 m(2); P = 0.50); GFR slopes (mean +/- SEM: -1.10 +/- 0.56
      versus -1.23 +/- 0.31 ml/min per 1.73 m(2) per year; P = 0.83); and 72-mo patient
      mortality (4.0 versus 4.0% [P = 0.95]; HR 0.96; 95% CI 0.28 to 3.31; P = 0.95),
      graft loss (6.8 versus 6.1% [P = 0.82]; HR 0.89; 95% CI 0.32 to 2.46; P = 0.83),
      incidence of persistent proteinuria (25.0 versus 27.4%; P = 0.72), late (>6 mo
      after transplantation) rejections (25.3 versus 21.2%; P = 0.53), and adverse
      events were similar on azathioprine (n = 124) and MMF (n = 124), respectively.
      Outcomes in the two groups were comparable also among patients with or without
      steroid therapy, considered separately. In kidney transplantation, the long-term
      risk/benefit profile of MMF and azathioprine therapy in combination with
      cyclosporine Neoral is similar. In view of the cost, standard immunosuppression
      regimens for kidney transplantation should perhaps include azathioprine rather
      than MMF.

PMID- 17460146
TI  - Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial
      growth factor-A activity during glomerular vascular development.
AB  - Crim1, a transmembrane cysteine-rich repeat-containing protein that is related to
      chordin, plays a role in the tethering of growth factors at the cell surface.
      Crim1 is expressed in the developing kidney; in parietal cells, podocytes, and
      mesangial cells of the glomerulus; and in pericytes that surround the arterial
      vasculature. A gene-trap mouse line with an insertion in the Crim1 gene
      (Crim1(KST264/KST264)) displayed perinatal lethality with defects in multiple
      organ systems. This study further analyzed the defects that are present within
      the kidneys of these mice. Crim1(KST264/KST264) mice displayed abnormal
      glomerular development, illustrated by enlarged capillary loops, podocyte
      effacement, and mesangiolysis. When outbred, homozygotes that reached birth
      displayed podocyte and glomerular endothelial cell defects and marked
      albuminuria. The podocytic co-expression of Crim1 with vascular endothelial
      growth factor-A (VEGF-A) suggested a role for Crim1 in the regulation of VEGF-A
      action. Crim1 and VEGF-A were shown to interact directly, providing evidence that
      cysteine-rich repeat-containing proteins can bind to non-TGF-beta superfamily
      ligands. Crim1(KST264/KST264) mice display a mislocalization of VEGF-A within the
      developing glomerulus, as assessed by immunogold electron microscopy and
      increased activation of VEGF receptor 2 (Flk1) in the glomerular endothelial
      cells, suggesting that Crim1 regulates the delivery of VEGF-A by the podocytes to
      the endothelial cells. This is the first in vivo demonstration of regulation of
      VEGF-A delivery and supports the hypothesis that Crim1 functions to regulate the
      release of growth factors from the cell of synthesis.

PMID- 17460147
TI  - Toll-like receptor 4 ligation on intrinsic renal cells contributes to the
      induction of antibody-mediated glomerulonephritis via CXCL1 and CXCL2.
AB  - Autoimmune diseases such as glomerulonephritis are exacerbated by infection. This
      study examined the effect of the Toll-like receptor 4 (TLR4) ligand lipid A on
      the development of heterologous nephrotoxic nephritis. Administration of
      nephrotoxic antibody resulted in significant glomerular neutrophil infiltration
      and albuminuria only when a TLR4 ligand was administered simultaneously. The
      contribution of TLR4 on renal cells and circulating leukocytes was assessed. Bone
      marrow chimeras were constructed with TLR4 only on renal cells or bone marrow
      derived cells. The administration of nephrotoxic serum and lipid A caused a
      neutrophil influx in both chimeric groups greater than in sham chimeras that were
      totally TLR4 deficient but significantly less than in sham chimeras that were
      totally TLR4 sufficient. Both chimeric groups had greater albuminuria than
      totally TLR4-deficient sham chimeras; however, the chimeras with TLR4 only on
      intrinsic renal cells had significantly less than the sham positive group. In
      situ hybridization showed expression of TLR4 mRNA in mesangial cells and
      glomerular epithelial cells. For investigation of the potential mechanism by
      which renal cells could contribute to disease exacerbation, mesangial cells were
      cultured and found to express mRNA for TLR4, and stimulation of wild-type and
      TLR4-deficient mesangial cells with LPS caused production of CXC chemokines by
      wild-type cells only. Treatment of chimeras with TLR4 present only on intrinsic
      renal cells with anti-CXCL1 and anti-CXCL2 antibody before disease induction
      significantly reduced renal neutrophil infiltration. These results show that TLR4
      on both circulating leukocytes and intrinsic renal cells contributes to the
      inflammatory effects of antibody deposition within the glomerulus, which depends
      at least in part on the production of CXC chemokines by intrinsic renal cells.

PMID- 17460148
TI  - Role for TGF-beta in cyclosporine-induced modulation of renal epithelial barrier
      function.
AB  - It was previously shown that cyclosporine A (CsA) increases transepithelial
      resistance in MDCK cells. Activation of the extracellular signal-regulated kinase
      1/2 (ERK1/2) mitogen-activated protein kinase (MAPK) cascade seems to be pivotal
      to the CsA-induced increase in transepithelial electrical resistance (TER). This
      study examined the role played by TGF-beta in mediating the CsA-induced
      activation of ERK1/2 and the resulting increase in TER in MDCK cells.
      Paracellular permeability across MDCK monolayers after various treatments was
      assessed by measurement of TER. TGF-beta secretion was measured by Western blot
      and ELISA. Activation of the ERK1/2 pathway and tight junction protein expression
      were also assessed by Western blot analysis. CsA increased production and
      secretion of TGF-beta and expression of the TGF-beta receptor II. Exogenous
      addition of TGF-beta1 activated ERK1/2 and increased TER across MDCK monolayers,
      both of which were attenuated by the MEK inhibitor U0126. Neutralizing antibodies
      against TGF-beta1 and the TGF-beta receptor II significantly reduced the CsA
      induced increase in TER. Both CsA and TGF-beta1 increased expression of tight
      junction proteins claudin-1 and zonula occludens 2. Inhibition of the p38 MAPK
      pathway also attenuated the TGF-beta1-induced increase in TER. The results
      presented here suggest that the CsA-induced modulation of paracellular
      permeability may be mediated, at least in part, by an increase in TGF-beta
      production.

PMID- 17460149
TI  - sigma(2)-receptor ligand-mediated inhibition of inwardly rectifying K(+) channels
      in the heart.
AB  - The sigma(2)-receptor agonist, ifenprodil, was suggested as an inhibitor of G
      protein-coupled inwardly rectifying potassium channels. Nevertheless, an analysis
      of the role of sigma(2) receptors in cardiac electrophysiology has never been
      done. This work aims i) to identify the roles of cardiac sigma(2) receptors in
      the regulation of cardiac K(+) channel conductances and ii) to check whether
      sigma(2)-receptor agonists exhibit class III antiarrhythmic properties. The
      sigma(2)-receptor agonists ifenprodil, threo-ifenprodil, LNP250A [threo-8-[1-(4
      hydroxyphenyl)-1-hydroxy-propan-2-yl]-1-phenyl-1,3,8-triazaspiro[4,5]decane-4
      one] (a derivative of ifenprodil devoid of alpha(1)-adrenergic and N-methyl-d
      aspartate glutamate receptor-blocking properties), and 1,3-di(2-tolyl)guanidine
      were used to discriminate the effects linked to sigma(2) receptors from those of
      the sigma(1) subtype, induced by (+/-)-N-allylnormetazocine (SKF-10,047). The
      sigma(2)-receptor antagonist 3-alpha-tropanyl-2(pCl-phenoxy)butyrate (SM-21) was
      employed to characterize sigma(2)-mediated effects in patch-clamp experiments. In
      rabbits, all sigma(2)-receptor agonists reduced phenylephrine-induced cardiac
      arrhythmias. They prolonged action potential duration in rabbit Purkinje fibers
      and reduced human ether-a-go-go-related gene (HERG) K(+) currents. (+)-SKF-10,047
      was completely inactive in the last two tests. The effects of threo-ifenprodil
      were not antagonized by SM-21. In HERG-transfected COS-7 cells, SM-21 potentiated
      the ifenprodil-induced blockade of the HERG current. These data suggest that
      sigma(2)-receptor ligands block I(Kr) and that this effect could explain part of
      the antiarrhythmic properties of this ligands family. Nevertheless, an
      interaction with HERG channels not involving sigma(2) receptors seems to share
      this pharmacological property. This work shows for the first time that particular
      caution has to be taken toward ligands with affinity for sigma(2) receptors. The
      repolarization prolongation and the early-afterdepolarization can be responsible
      for "torsades de pointe" and sudden cardiac death.

PMID- 17460150
TI  - Rapid stimulation of presynaptic serotonin transport by A(3) adenosine receptors.
AB  - The inactivation of synaptic serotonin (5-hydroxytryptamine, 5-HT) is largely
      established through the actions of the presynaptic, antidepressant-sensitive 5-HT
      transporter (SERT, SLC6A4). Recent studies have demonstrated post-translational
      regulation of SERT mediated by multiple Ser/Thr kinases, including protein
      kinases C and G (PKC and PKG) and p38 mitogen-activated protein kinase (MAPK), as
      well as the Ser/Thr phosphatase PP2A. Less well studied are specific surface
      receptors that target these signaling pathways to control SERT surface expression
      and/or catalytic rates. Using rat basophilic leukemia 2H3 cell line (RBL-2H3), we
      previously established that activation of A(3) adenosine receptors (A(3)AR)
      stimulates SERT activity via both PKG and p38 MAPK (Zhu et al., 2004a). Whether
      A(3)ARs regulate SERT in the central nervous system (CNS) is unknown. Here we
      report that the A(3)AR agonist N(6)-(3-iodobenzyl)-N-methyl-5'carbamoyladenosine
      (IB-MECA) rapidly (10 min) and selectively stimulates 5-HT transport in mouse
      midbrain, hippocampal, and cortical synaptosomes. IB-MECA-induced stimulation of
      5-HT uptake is blocked by the selective A(3)AR antagonist 3-ethyl-5-benzyl-2
      methyl-phenylethynyl-6-phenyl-1,4(+/-)dihydropyridine-3,5-dicarboxylate (MRS1191)
      and is absent from synaptosomes prepared from A(3)AR knockout mice. Kinetic
      analyses demonstrate that IB-MECA induces an increase of 5-HT transport V(max)
      with no significant change in K(m). As in RBL-2H3 cells, IB-MECA stimulation of
      synaptosomal 5-HT uptake can be blocked by preincubation with PKG antagonists N
      [2-(methylamino)ethy]-5-isoquinoline-sulfonamide (H8) and DT-2
      (YGRKKRRQRRRPPLRK(5)H), as well as by the p38 MAPK inhibitor SB203580 [4-(4
      fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-1H-imidazole].
      Chronoamperometry studies in the anesthetized rat hippocampus support a role for
      A(3)ARs in SERT regulation in vivo. Together, these results identify a novel,
      region-specific action of CNS A(3)ARs in the modulation of SERT-mediated 5-HT
      transport that may be relevant for the etiology and/or therapy of 5-HT-linked
      brain disorders.

PMID- 17460151
TI  - Attenuation of ozone-induced airway inflammation and hyper-responsiveness by c
      Jun NH2 terminal kinase inhibitor SP600125.
AB  - Ozone has potent oxidizing properties, and exposure to ozone causes airway hyper
      responsiveness (AHR) and lung inflammation. We determined the importance of c-Jun
      NH(2) terminal kinase (JNK), a member of the mitogen-activated protein kinase
      pathway, in ozone-induced AHR and inflammation. SP600125 [anthra[1,9-cd] pyrazol
      6 (2H)-one], a specific JNK inhibitor (30 mg/kg) or vehicle, was administered by
      intraperitoneal injection before and after ozone exposure (3 ppm for 3 h).
      SP600125 significantly reduced total cells, and neutrophils in bronchoalveolar
      fluid recovered at 20 to 24 h after exposure and inhibited ozone-induced AHR.
      Ozone exposure induced activation of JNK in the lung as measured by the
      expression of phosphorylated-c-Jun, an effect abolished by SP600125. Gene
      microarray analysis revealed that ozone increased the expression of over 400
      genes by more than 2-fold, including interleukin-6 (IL-6), CXCL1 (keratinocyte
      cytokine), and CCL2 (monocyte chemoattractant protein-1). SP600125 modulated the
      expression of a subset of 29 ozone-induced genes; IL-6 and CCL2 expression were
      further increased, whereas the expression of metallothionein 1, hemopexin, and
      mitogen-activated 3 kinase 6 was decreased in SP600125-treated ozone-exposed
      mice. Changes in mRNA for IL-6, CXCL1, and CCL2 were confirmed by real-time
      polymerase chain reaction. Ozone also decreased the expression of over 500 genes,
      with the most potent effect on angiopoietin-1. SP600125 modulated the expression
      of 15 of these genes, and in particular, SP600125 reversed ozone-induced decrease
      in expression of the redox-sensitive transcription factor, hypoxia-induced factor
      1alpha. This study highlights an important role for JNK in response to oxidative
      stress through modulation of specific inflammatory and redox mediators.
      Inhibition of JNK with small molecule kinase inhibitors may be a means of
      reducing ozone-induced inflammation and AHR.

PMID- 17460152
TI  - CD163-expressing monocytes constitute an endotoxin-sensitive Hb clearance
      compartment within the vascular system.
AB  - Hemoglobin (Hb) is released into the circulation during intravascular hemolysis
      and exerts toxic effects through oxidative damage and NO scavenging. According to
      the traditional concept of Hb clearance, free Hb is bound to the plasma protein
      haptoglobin (Hp), and the Hb-Hp complexes are cleared by liver and spleen
      macrophages via the Hb scavenger receptor CD163. Using a novel whole blood assay,
      we demonstrate that clearance of Hb-Hp is also mediated by CD14(high)/CD64(high)
      peripheral blood monocytes, which express CD163. Hb-Hp uptake by these cells is
      Ca(2+)-dependent and is abrogated by the addition of CD163-blocking antibodies.
      Accordingly, LPS treatment reduces monocyte surface CD163 and impairs Hb-Hp
      uptake. Monocytes likely mediate Hp-Hb uptake in vivo, as a high expression of
      the heme breakdown enzyme heme oxygenase-1 was observed in CD163(+) monocytes but
      not in other leukocyte populations obtained from healthy blood donors. We propose
      that CD163-mediated Hb-Hp uptake by peripheral blood monocytes constitutes an Hb
      Hp clearance pathway, which acts at the site of intravascular hemolysis to reduce
      Hb-Hp circulation time and toxicity. Disruption of monocyte Hb-Hp clearance may
      increase Hb-Hp toxicity and contribute to the pathogenesis of systemic
      inflammatory diseases associated with reduced monocyte CD163 expression.

PMID- 17460153
TI  - APOE epsilon 4 allele is associated with cognitive impairment in patients with
      multiple sclerosis.
AB  - BACKGROUND: The role of apolipoprotein E (APOE) polymorphism has been well
      recognized in other cognitive neurodegenerative disorders, such as Alzheimer
      disease. Its role in multiple sclerosis (MS) is less clear, though studies
      indicate that 40% to 60% of patients with MS have evidence of cognitive
      impairment. OBJECTIVE: To determine whether there is an association between APOE
      epsilon 4 and cognitive deficits in MS. METHODS: We performed a standardized
      battery of neuropsychological tests investigating the four cognitive domains
      commonly impaired in MS and assessed the association of the presence of APOE
      epsilon 4 with cognition in MS. RESULTS: A strong association was found between
      the presence of APOE epsilon 4 and cognitive deficits in patients with MS,
      particularly in the domains of learning and memory. This association was
      strongest in our youngest cohort (age 31 to 40) of patients with MS. CONCLUSIONS:
      APOE epsilon 4 is significantly associated with cognitive impairment in patients
      with multiple sclerosis (MS). However, the modest effects do not justify APOE
      genotyping of patients with MS in clinical practice.

PMID- 17460154
TI  - Evidence report: the medical treatment of ocular myasthenia (an evidence-based
      review): report of the Quality Standards Subcommittee of the American Academy of
      Neurology.
AB  - OBJECTIVE: To perform a systematic review of the relevant literature and to
      provide evidence-based guidelines for the medical treatment of ocular myasthenia.
      METHODS: Medline, EMBASE, and the Cochrane Neuromuscular Disease Group Register
      were searched for articles of possible relevance to the medical treatment of
      ocular myasthenia. The titles and abstracts of all articles, as well as the full
      texts of all potentially relevant manuscripts, were read by both reviewers.
      Experts in the field were also contacted to identify other published or
      unpublished literature. All articles were evaluated using predefined criteria to
      evaluate their methodologic quality. Data from these articles were extracted to
      address two questions: 1) Are there any effective treatments for symptoms of
      ocular myasthenia? 2) Are there any treatments that reduce the risk of
      progression from ocular to generalized myasthenia gravis (MG)? RESULTS: A single
      randomized controlled trial compared the efficacy of intranasal neostigmine to
      placebo for the treatment of ocular symptoms. Methodologic limitations of this
      study preclude any firm conclusions. A second randomized controlled trial
      compared the efficacy of corticotropin with placebo, but outcome was reported in
      terms of a quantification of the range of eye movements. For this reason, the
      results of the second study could not be used to address the issues of
      improvement in ocular symptoms or the risk of progression to generalized MG. This
      review did not identify any randomized controlled trials addressing the risk of
      progression to generalized MG but did identify five observational studies
      reporting the effects of corticosteroids on progression to generalized MG, two of
      which also reported the effects of azathioprine. RECOMMENDATIONS: The absence of
      high-quality evidence means that it is not possible to make any evidence-based
      recommendations regarding the effects of cholinesterase inhibitors,
      corticosteroids, or other immunosuppressive agents with respect to improvement of
      ocular symptoms. There is similarly an absence of evidence regarding the effects
      of cholinesterase inhibitors on the risk of progression to generalized myasthenia
      gravis (MG). Based on data from several observational studies, corticosteroids
      and azathioprine are of uncertain benefit in terms of their effect on the risk of
      progression to generalized MG.

PMID- 17460155
TI  - Familial occipitotemporal lobe epilepsy and migraine with visual aura: linkage to
      chromosome 9q.
AB  - OBJECTIVE: To map the disease-causing locus in a large Belgian family with
      occipitotemporal lobe epilepsy associated with migraine with visual aura and to
      describe the clinical, electrophysiologic, and imaging characteristics. METHODS:
      DNA samples from 21 family members were obtained and an 8 cM density genome-wide
      scan was performed. The authors interviewed 21 individuals and performed
      interictal EEG in 14 and brain MRI in 13 individuals. RESULTS: Nine at risk
      family members and one deceased individual had epilepsy with occipital and
      temporal lobe symptomatology, variable age at onset, usually good prognosis, no
      epileptic EEG features, and normal brain MRI. Five of the 10 patients had a
      history of migraine with aura (p = 0.0026). Seizures and migraine attacks
      occurred as separate episodes in all but one patient. Three patients described
      light flashes both as epileptic and migraine aura. Epilepsy and migraine started
      at the same age in three patients and remitted simultaneously in two. The
      epileptic phenotype had a dominant mode of inheritance with a reduced penetrance
      of 75%. A conclusive two-point lod score of 3.3 was obtained for marker D9S257 at
      recombination fraction zero. Haplotype analysis defined a candidate region of
      9.95 cM (5.96 Mb) between markers GATA152H04 and D9S253 located at chromosome
      9q21-q22 based upon recombinations in affected individuals. CONCLUSIONS: The
      clinical association in this family of occipitotemporal lobe epilepsy and
      migraine with visual aura and the conclusive linkage of the occipitotemporal lobe
      epilepsy/migraine with aura trait to a single locus suggests a common monogenic
      gene defect.

PMID- 17460156
TI  - Psychological or physiological: why are tetraplegic patients content?
AB  - OBJECTIVE: To assess the effects of spinal cord injury (SCI) on perceived health
      related quality of life (QOL). BACKGROUND: SCI is physically disabling, socially
      handicapping, and romantically limiting. Nevertheless, little is known about post
      SCI neurocognitive and psychosocial life. Better understanding of the cognitive
      and emotional worlds of SCI patients is essential to better address and meet
      their needs and expectations. METHODS: Twenty subjects with high-cord (T6 and
      above) complete (American Spinal Injury Association [ASIA] A) SCI (High SCI) were
      compared with 10 subjects with low-cord (T7 and below) ASIA A SCI (Low SCI) and
      with 11 Able-Bodied control subjects. Satisfaction with Life and Short Form-36
      instruments were used to assess physical and emotional aspects of QOL. Analyses
      of variance were used to assess potential differences across groups. RESULTS:
      Overall, satisfaction with life was the same among the groups. Expectedly, High
      SCI and Low SCI subjects reported lower physical functioning than Able-Bodied
      subjects (p < 0.0001). But, oddly, there were no differences in perceived
      physical role, physical health, or social functioning. Furthermore, High SCI
      subjects reported better perceived mental health than Able-Bodied control
      subjects (p = 0.004) and a trend over Low SCI subjects (p = 0.06), better
      perceived emotional role in society (p = 0.02), and greater vitality (p = 0.01)
      than Low SCI subjects and Able-Bodied subjects. CONCLUSIONS: Despite severe
      physical impairment and disability and frequent medical complications, subjects
      with complete spinal cord injury at high anatomic levels report better than
      average quality of life, being overall content. Reasons for these findings are
      unclear. Psychological adaptive reactions are likely, but the possible role of
      physiologic and neurocognitive changes needs further exploration.

PMID- 17460157
TI  - Altered arterial function in migraine of recent onset.
AB  - OBJECTIVE: Migraine is associated with cardiovascular disorders but the
      underlying mechanisms are unknown. Arterial structure and function are important
      determinants of cardiovascular morbidity and mortality. The aim of the present
      study was to assess arterial properties in patients with migraine of recent
      onset. METHODS: In a cross-sectional study, structural and functional arterial
      properties were assessed using ultrasound and applanation tonometry in 50
      patients with a history of migraine >1 and <6 years during a headache-free
      interval and 50 age- and gender-matched subjects without a history of migraine.
      RESULTS: Brachial artery diameter (4.82 +/- 0.93 mm vs 5.39 +/- 0.89 mm, p =
      0.01) and compliance (0.30 +/- 0.17 mm(2)/kPa vs 0.37 +/- 0.19 mm(2)/kPa, p =
      0.02) were decreased in migraine patients compared with controls. Femoral artery
      compliance was decreased in migraine patients (1.19 +/- 0.55 mm(2)/kPa vs 1.42 +/
      0.59 mm(2)/kPa, p = 0.04). Carotid arterial wall properties were similar between
      groups. Aortic augmentation index was increased in migraine patients (4 +/- 10%
      vs -1 +/- 10%, adjusted p = 0.04). Flow-mediated vasodilation of the brachial
      artery (normalized to peak shear rate) was decreased in patients with migraine
      (29 +/- 15 vs 37 +/- 15 10(-3)%. sec, p = 0.006). CONCLUSION: Functional arterial
      properties are altered in patients with migraine of recent onset.

PMID- 17460158
TI  - Naproxen and celecoxib do not prevent AD in early results from a randomized
      controlled trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of naproxen and celecoxib for the
      primary prevention of Alzheimer disease (AD). METHODS: Randomized, placebo
      controlled, double-masked clinical trial conducted at six US dementia research
      clinics. Volunteers aged 70+ years, with cognitive screening scores above
      designated cut-offs and a family history of AD, were randomly assigned to
      celecoxib 200 mg BID, naproxen sodium 220 mg BID, or placebo. Enrollment began in
      early 2001. The main outcome measure was diagnosis of AD after randomization.
      RESULTS: On December 17, 2004, treatments were suspended. Events while on
      treatment yielded hazard ratios vs placebo of 1.99 (95% CI 0.80 to 4.97; p =
      0.14) for celecoxib and 2.35 (0.95 to 5.77; p = 0.06) for naproxen. Imperfect
      screening measures led to enrollment of 7 individuals with dementia and 46 others
      with milder cognitive syndromes. Their (prevalent) illness was detected at
      enrollment and diagnosed within 6 months following randomization. Secondary
      analyses that excluded the 7 cases of prevalent dementia showed increased hazard
      ratios for AD with both treatments. Neither treatment produced a notable effect
      on the incidence of milder cognitive syndromes. CONCLUSIONS: These results do not
      support the hypothesis that celecoxib or naproxen prevent Alzheimer dementia, at
      least within the early years after initiation of treatment. Masked long-term
      follow-up of these participants will be essential.

PMID- 17460159
TI  - Reproductive-tactic-specific variation in sperm swimming speeds in a shell
      brooding cichlid.
AB  - Theory predicts that males experiencing elevated levels of sperm competition will
      invest more in gonads and produce faster-swimming sperm. Although there is ample
      evidence in support of the first prediction, few studies have examined sperm
      swimming speed in relation to sperm competition. In this study, we tested these
      predictions from sperm competition theory by examining sperm characteristics in
      Telmatochromis vittatus, a small shell-brooding cichlid fish endemic to Lake
      Tanganyika. Males exhibit four different reproductive tactics: pirate,
      territorial, satellite, and sneaker. Pirate males temporarily displace all other
      competing males from a shell nest, whereas sneaker males always release sperm in
      the presence of territorial and satellite males. Due to the fact that sneakers
      spawn in the presence of another male, sneakers face the highest levels of sperm
      competition and pirates the lowest, whereas satellites and territorials
      experience intermediate levels. In accordance with predictions, sperm from
      sneakers swam faster than sperm from males adopting the other reproductive
      tactics, whereas sperm from pirates was slowest. Interestingly, we were unable to
      detect any variation in sperm tail length among these reproductive tactics. Thus,
      sperm competition appears to have influenced sperm energetics in this species
      without having any influence on sperm size.

PMID- 17460161
TI  - Biological aging is no longer an unsolved problem.
AB  - The belief that aging is still an unsolved problem in biology is no longer true.
      Of the two major classes of theories, the one class that is tenable is derivative
      of a single common denominator that results in only one fundamental theory of
      aging. In order to address this complex subject, it is necessary to first define
      the four phenomena that characterize the finitude of life. These phenomena are
      aging, the determinants of longevity, age-associated diseases, and death. There
      are only two fundamental ways in which age changes can occur. Aging occurs either
      as the result of a purposeful program driven by genes or by events that are not
      guided by a program but are stochastic or random, accidental events. The weight
      of evidence indicates that genes do not drive the aging process but the general
      loss of molecular fidelity does. Potential longevity is determined by the
      energetics of all molecules present at and after the time of reproductive
      maturation. Thus, every molecule, including those that compose the machinery
      involved in turnover, replacement, and repair, becomes the substrate that
      experiences the thermodynamic instability characteristic of the aging process.
      However, the determinants of the fidelity of all molecules produced before and
      after reproductive maturity are the determinants of longevity. This process is
      governed by the genome. Aging does not happen in a vacuum. Aging must be the
      result of changes that occur in molecules that have existed at one time with no
      age changes. It is the state of these pre-existing molecules that governs
      longevity determination. The distinction between the aging process and age
      associated disease is not only based on the molecular definition of aging
      described above but it is also rooted in several practical observations. Unlike
      any disease, age changes (a) occur in every multicellular animal that reaches a
      fixed size at reproductive maturity, (b) cross virtually all species barriers,
      (c) occur in all members of a species only after the age of reproductive
      maturation, (d) occur in all animals removed from the wild and protected by
      humans even when that species probably has not experienced aging for thousands or
      even millions of years, (e) occur in virtually all animate and inanimate matter,
      and (f) have the same universal molecular etiology, that is, thermodynamic
      instability. Unlike aging, there is no disease or pathology that shares these six
      qualities. Because this critical distinction is poorly understood, there is a
      continuing belief that the resolution of age-associated diseases will advance our
      understanding of the fundamental aging process. It will not. The distinction
      between disease and aging is also critical for establishing science policy
      because although policy makers understand that the funding of research on age
      associated diseases is an unquestioned good, they also must understand that the
      resolution of age-associated diseases will not provide insights into
      understanding the fundamental biology of age changes. They often believe that it
      will and base decisions on that misunderstanding. The impact has been to fund
      research on age-associated diseases at several orders of magnitude greater than
      what is available for research on the biology of aging. There is an almost
      universal belief by geriatricians and others that the greatest risk factor for
      all of the leading causes of death is old age. Why then are we not devoting
      significantly greater resources to understanding more about the greatest risk
      factor for every age-associated pathology by attempting to answer this
      fundamental question-"What changes occur in biomolecules that lead to the
      manifestations of aging at higher orders of complexity and then increase
      vulnerability to all age-associated pathology?"

PMID- 17460162
TI  - Modalities of gene action predicted by the classical evolutionary biological
      theory of aging.
AB  - What might now be referred to as the "classical" evolutionary biological theory
      of why we age has had a number of serious challenges in recent years. While the
      theory might therefore have to be modified under certain circumstances, in the
      author's opinion, it still provides the soundest theoretical basis for thinking
      about how we age. Nine modalities of gene action that have the potential to
      modulate processes of aging are reviewed, including the two most widely reviewed
      and accepted concepts ("antagonistic pleiotropy" and "mutation accumulation").
      While several of these nine mechanisms can be regarded as derivatives of the
      antagonistic pleiotropic concept, they frame more specific questions for future
      research. Such research should pursue what appears to be the dominant factor in
      the determination of intraspecific variations in longevity-stochastic mechanisms,
      most likely based upon epigenetics. This contrasts with the dominant factor in
      the determination of interspecific variations in longevity-the constitutional
      genome, most likely based upon variations in regulatory loci.

PMID- 17460163
TI  - Genetics of healthy aging in Europe: the EU-integrated project GEHA (GEnetics of
      Healthy Aging).
AB  - The aim of the 5-year European Union (EU)-Integrated Project GEnetics of Healthy
      Aging (GEHA), constituted by 25 partners (24 from Europe plus the Beijing
      Genomics Institute from China), is to identify genes involved in healthy aging
      and longevity, which allow individuals to survive to advanced old age in good
      cognitive and physical function and in the absence of major age-related diseases.
      To achieve this aim a coherent, tightly integrated program of research that
      unites demographers, geriatricians, geneticists, genetic epidemiologists,
      molecular biologists, bioinfomaticians, and statisticians has been set up. The
      working plan is to: (a) collect DNA and information on the health status from an
      unprecedented number of long-lived 90+ sibpairs (n = 2650) and of younger
      ethnically matched controls (n = 2650) from 11 European countries; (b) perform a
      genome-wide linkage scannning in all the sibpairs (a total of 5300 individuals);
      this investigation will be followed by linkage disequilibrium mapping (LD
      mapping) of the candidate chromosomal regions; (c) study in cases (i.e., the 2650
      probands of the sibpairs) and controls (2650 younger people), genomic regions
      (chromosome 4, D4S1564, chromosome 11, 11.p15.5) which were identified in
      previous studies as possible candidates to harbor longevity genes; (d) genotype
      all recruited subjects for apoE polymorphisms; and (e) genotype all recruited
      subjects for inherited as well as epigenetic variability of the mitochondrial DNA
      (mtDNA). The genetic analysis will be performed by 9 high-throughput platforms,
      within the framework of centralized databases for phenotypic, genetic, and mtDNA
      data. Additional advanced approaches (bioinformatics, advanced statistics,
      mathematical modeling, functional genomics and proteomics, molecular biology,
      molecular genetics) are envisaged to identify the gene variant(s) of interest.
      The experimental design will also allow (a) to identify gender-specific genes
      involved in healthy aging and longevity in women and men stratified for ethnic
      and geographic origin and apoE genotype; (b) to perform a longitudinal survival
      study to assess the impact of the identified genetic loci on 90+ people
      mortality; and (c) to develop mathematical and statistical models capable of
      combining genetic data with demographic characteristics, health status,
      socioeconomic factors, lifestyle habits.

PMID- 17460164
TI  - Postponement of postmenopausal mortality acceleration in low-mortality
      populations.
AB  - Mortality analyses commonly disregard postmenopausal acceleration. This study
      examined period log mortality in World Health Organization (WHO) data for 34 low
      mortality countries in 2000, demonstrating significant gradient increases for
      women (33/34 countries) and men (22/34), from a later age than previously
      reported, dividing the postmenopausal period into phases. "Break points" were
      identified as intersects of lines of best fit to these and the same approach was
      used in analysis of Human Mortality Database data for 19 countries. There has
      been an upward migration of about 10 years in female age at break point since
      1850. Male data flipped from mortality acceleration to deceleration and back in
      the late 20th century with no apparent shift in break point. Altered age at
      mortality acceleration appears genuine, gender-specific, and internationally
      consistent. Its timing prompts the hypothesis that it may relate to falling
      fertility.

PMID- 17460165
TI  - Cross-talk between aging and cancer: the epigenetic language.
AB  - The risk of having cancer increases with age probably because progenitor cells
      from mature organisms accumulate enough molecular lesions to evade the
      homeostatic control of their tissular contexts. Molecular lesions can be genetic
      (mutations, deletions, or translocations) and/or epigenetic. Epigenetic
      signaling, including DNA methylation and histone modification, is essential for
      normal development and becomes altered during Aging and by cancer. Several
      epigenetic alterations, such as global hypomethylation and CpG island
      hypermethylation, are progressively accumulated during Aging and directly
      contribute to cell transformation. Intriguingly, others, such as those involved
      in the control of telomere length and several epigenetic enzymes belonging to the
      family of nicotinamide adenine dinucleotide (NAD)(+) dependent deacetylases known
      as sirtuins, exhibit a well-defined progression during Aging that is dramatically
      reverted in transformed cells. We discuss the biological significance of both
      groups of epigenetic modifications in terms of their relative contribution to
      ontogenic development, senescence, and cell proliferation.

PMID- 17460166
TI  - Molecular chaperones and the epigenetics of longevity and cancer resistance.
AB  - The inherent immortality of embryonic stem cells demonstrates that replicative
      senescence as possibly the aging of species are epigenetic phenomena. The
      cellular level of expression of the housekeeping molecular chaperones correlates
      with longevity and cancer resistance of species. The chaperones are cancer
      antagonists by acting as genetic buffers, stabilizing the normal phenotype.
      Probably the progressive age-related silencing of the housekeeping genes
      contributes to the phenotype of aging, with the associated increase in cancer
      incidence. The present review concerns epigenetic chemical, immunological, and
      hormonal mechanisms, activating chaperone- and immune-response genes, which have
      proved effective in increasing longevity and cancer resistance. The relation of
      steroid hormone levels to species longevity, the anticarcinogenic activity of
      pregnancy hormones, and the influence of hormones on the longevity of social
      insects, illustrates the importance of hormonal mechanisms for the activation of
      longevity genes.

PMID- 17460167
TI  - Regulation of human life histories: the role of the inflammatory host response.
AB  - Most species with a long life span have few offspring while species with a short
      life span have many offspring. This evolutionary trade-off between fertility and
      body maintenance, based on the theory of r/K-selection, is a central theme in the
      theory of life history regulation. This trade-off is not only found between
      various species but also between individuals within one species. There is
      accumulating evidence for this trade-off in humans. We hypothesize that the
      innate immune system is a critical factor skewing an individual into the
      direction of either a high fertility or better maintenance strategy. As over
      thousands of years human survival has been highly dependent on resistance to
      infectious diseases, genetic adaptations resulting in inflammatory responses were
      favored. An inflammatory host response is critical to fight infection necessary
      to survive up to reproductive age. An inflammatory host response is also
      negatively associated with fertility and can explain for the trade-off between
      fertility and body maintenance. After human reproductive age, these inflammatory
      responses contribute also to development of chronic degenerative diseases. These
      will especially become apparent in affluent societies where the majority of
      individuals reach old age. Identifying the inflammatory host response as a
      critical factor both in the regulation of human life histories and in the
      occurrence of chronic diseases at old age implies means for intervention allowing
      individuals to live healthier for longer.

PMID- 17460168
TI  - Do membrane rafts contribute to human immunosenescence?
AB  - Aging is associated with an alteration of the immune response called
      immunosenescence. It is now well accepted that all parts of the immune system,
      the adaptive as well as the innate, undergo immunosenescence. However, the
      adaptive immune response and especially T cell functions are the most affected by
      aging. Aging is associated with profound changes in lymphocytes subpopulations,
      however, the functional changes within these subsets are more important to
      elucidate. Indeed, T cells present functional modifications resulting in a
      decreased clonal expansion and interleukin-2 (IL-2) production. So there should
      be an alteration in the activation process of T cells with aging involving the T
      cell receptor (TCR) and CD28 receptor signaling cascades. The alterations in
      membrane rafts composition and function can underline this altered activation of
      T cells with aging and then contribute to human immunosenescence. The
      experimental data in favor of this hypothesis will be reviewed.

PMID- 17460169
TI  - Zinc and inflammatory/immune response in aging.
AB  - Life-long antigenic burden determines a condition of chronic inflammation, with
      increased lymphocyte activation and proinflammatory cytokine production. A large
      number of studies have documented changes in zinc metabolism in experimental
      animal models of acute and chronic inflammation and in human chronic inflammatory
      conditions. In particular, modification of zinc plasma concentration, as well as
      intracellular disturbance of antioxidant intracellular pathways, has been found
      in aging and in some age-related diseases. Zinc deficiency is diffused in aged
      individuals in order to avoid meat and other high zinc content foods due to fear
      of cholesterol. Rather, they increase the consumption of refined wheat products
      that lack zinc and other critical nutrients as a consequence of the refining
      process. On the other hand, plasma zinc concentration is influenced by
      proinflammatory cytokines (IL-6 and TNF-alpha) and by metallothioneins (MT)
      homeostasis, which is in turn affected by proinflammatory cytokines. MT increase
      in aging and chronic inflammation allowing a continuous sequestration of
      intracellular zinc with subsequent low zinc ion availability against stressor
      agents and inflammation. This phenomenon leads to an impaired inflammatory/immune
      response in the elderly. A major target of zinc is NF-kappaB, a transcription
      factor critical for the expression of proinflammatory cytokines whose production
      is regulated by extra- and intracellular activating and inhibiting factors
      interacting with the regulatory elements on cytokine genes. Effects of zinc on
      translocation of NF-kappaB have been attributed to the suppression of
      phosphorylation and degradation of the inhibitory proteins (A20) that normally
      sequester it in the cytoplasm. Moreover, this factor and A20 are regulated by
      specific genes involved in inflammation and by intracellular zinc ion
      availability. So, it is not so surprising that zinc deficiency is constantly
      observed in chronic inflammation, such as in old individuals. On the other hand,
      cytokine genes are highly polymorphic and some of these polymorphisms are
      associated with atherosclerosis and diabetes type 2. Therefore, zinc turnover,
      via MT homeostasis, in individuals genetically predisposed to a dysregulation of
      the inflammatory/immune response may play a crucial role in causing possible
      adverse events with the appearance of age-related diseases.

PMID- 17460170
TI  - Genetics of inflammation in age-related atherosclerosis: its relevance to
      pharmacogenomics.
AB  - In response to tissue injury elicited by trauma or infection, the inflammatory
      response, as a complex network of molecular and cellular interactions, sets an
      answer directed to facilitate a return to physiological homeostasis and tissue
      repair. The role of the genetic background and the subsequent predisposition
      toward the extent of the inflammatory response is determined by gene variability
      encoding endogenous mediators involved in the inflammatory pathway. Due to its
      clinical relevance, the genetics of inflammation in aging will be studied using
      an inflammatory disease like atherosclerosis as an example. Several studies have
      reported a significant difference in distribution, between patients and controls,
      of genes involved in inflammation. So, the proinflammatory alleles are
      underrepresented in control subjects and overrepresented in patients affected by
      atherosclerosis. These studies will allow building a risk profile that
      potentially enables the early identification of individuals susceptible to
      disease and the possible design or use of drug at the right dose for a desired
      effect, that is, a pharmacogenomic approach for this disease.

PMID- 17460171
TI  - PECAM-1/CD31 in infarction and longevity.
AB  - Inflammation has recently proven to be associated with the pathogenesis of
      atherosclerosis and inflammatory genes are good candidates for the risk of
      developing atherosclerosis. The early phase of atherosclerosis involves the
      recruitment of inflammatory cells from the circulation and their transendothelial
      migration. This process is mainly mediated by cellular adhesion molecules, which
      are expressed by the vascular endothelium and by circulating leukocytes in
      response to several inflammatory stimuli. Adhesion of circulating cells to the
      arterial surface is among the first detectable events in atherogenesis. Cellular
      adhesion molecules, expressed by the vascular endothelium and by circulating
      leukocytes, mediate cell recruitment and their transendothelial migration.
      Platelet endothelial cellular adhesion molecule-1 (PECAM-1/CD31), involved in
      this migration, has been associated with the developmental course of
      atherosclerosis. Studies have investigated an association between coronary heart
      disease (CHD) and single nucleotide polymorphisms (SNP) located in functionally
      important domains of the PECAM-1/CD31 gene, with contrasting results. In
      particular, we previously analyzed for the following PECAM-1/CD31 SNP: Val125Leu,
      Asn563Ser, and Gly670Arg. The frequency of the Gly670Arg polymorphism was
      significantly higher in patients with myocardial infarction (MI), whereas the
      frequencies of the other two SNP (Leu125Val and Ser563Asn) were not significantly
      different between patients and controls. To check the validity of our results, we
      have analyzed the distribution of these SNP in centenarian men (age >99) from our
      homogeneous Sicilian population, since our previous studies have demonstrated
      that alleles associated with MI susceptibility are not included in the genetic
      background favoring longevity. We showed, as regard to polymorphisms of PECAM
      1/CD31, that there were no significant differences between male patients affected
      by MI, male controls, and male centenarians. According to our hypothesis present
      results seemingly do not support a role for these SNP in conferring the
      susceptibility to MI at least in this Italian population.

PMID- 17460172
TI  - Plasma levels of apolipoprotein E and risk of stroke in old age.
AB  - Recently, high plasma apoE levels have been shown to be related to increased
      cardiovascular mortality, independent of APOE genotype. Here we studied the
      association of plasma apoE levels with risk of stroke. Within the Leiden 85-plus
      Study, a prospective population-based study of 561 subjects aged 85 years, we
      measured plasma apoE level and determined APOE genotype at base line. The
      presence of stroke in the medical history and the incidence of stroke during a 5
      year follow-up period were assessed by interviewing treating physicians. At base
      line, an increase of one standard deviation (SD) of plasma apoE level associated
      with a 1.47-fold higher risk of a history of stroke (P = 0.025). During follow
      up, an increase of one SD of plasma apoE level associated with an increased risk
      of stroke (risk of stroke: 1.58, P = 0.010). This association was also observed
      in epsilon3epsilon3- (1.95, P = 0.002) and epsilon3epsilon4 carriers (3.01, P =
      0.008), but not in epsilon2epsilon3 carriers (0.62, P = 0.440). In conclusion, in
      old age, except for epsilon2-allele carriers, high plasma apoE levels are
      associated with a higher risk of stroke, independent of APOE genotype, plasma
      levels of lipids, and other cardiovascular risk factors.

PMID- 17460173
TI  - Plasma levels of apolipoprotein E and cognitive function in old age.
AB  - The relationship between structural variants of the apolipoprotein E gene, APOE
      epsilon2/epsilon3/epsilon4, and dementia is well established, whereas the
      relationship of plasma apoE levels with dementia is less clear. Plasma apoE
      levels are under tight genetic control but vary widely within the various
      genotypes indicating that the APOE epsilon2/epsilon3/epsilon4 locus explains only
      a small fraction of this variation. Here we studied the association of plasma
      apolipoprotein E (apoE) levels with cognitive function in the elderly population
      at large. Within the Leiden 85-plus Study, a prospective population-based study
      of subjects aged 85 years, we measured plasma apoE level and genotype at base
      line. During a 5-year follow-up period, cognitive function was annually assessed
      using the Mini Mental State Examination (MMSE) and a standardized
      neuropsychological test battery. Among epsilon3epsilon3 carriers (n = 324), high
      plasma apoE levels associated with impaired global cognitive function (-1.10
      points change in MMSE score per one standard deviation increase of plasma apoE
      level, P = 0.001), as well as lower attention (P = 0.064), speed and memory
      function (all P < 0.05). Adjustment for cardiovascular risk factors and exclusion
      of all subjects who suffered a stroke did not materially change the associations.
      Similar estimates were obtained in epsilon3epsilon4 carriers (n = 100), but not
      in epsilon2epsilon3 carriers (n = 90). We conclude that in old age, in non
      epsilon2-allele carriers, high plasma apoE levels are associated with cognitive
      impairments, independent of genotype, cardiovascular risk factors, and stroke.

PMID- 17460174
TI  - CCR5 receptor: biologic and genetic implications in age-related diseases.
AB  - The CC chemokine receptor 5 (CCR5) is a member of CC-chemokine receptor family.
      CCR5 has the characteristic structure of a seven transmembrane G protein-coupled
      receptor (GPCR), which regulates trafficking and effector functions of
      memory/effector Th1 cells, macrophages, NK cells, and immature dendritic cells.
      CCR5 and its ligands are important molecules in viral pathogenesis. CCR5
      represents the co-receptor for macrophage (M) and dual (T cell and M)-tropic
      immunodeficiency viruses. Recent evidence has also demonstrated the role of CCR5
      in a variety of human diseases, ranging from infectious and inflammatory diseases
      to cancer. In this article, we describe the involvement of CCR5 in two age
      related diseases, atherosclerosis and Alzheimer's disease, suggesting a possible
      role of chemokine system on these diseases' pathophysiology. Finally, we review
      the data on the probable association between CCR5Delta32 deletion and
      cardiovascular diseases and Alzheimer's disease.

PMID- 17460175
TI  - Lumbar spinal stenosis in elderly patients.
AB  - Over a 3-year period in our clinic, surgeons operated on 32 persons over 65 years
      old with lumbar spinal stenosis. This article presents the retrospective analysis
      of the clinical, radiological, and short-term surgical outcomes. The stenosis
      seen most commonly among the elderly develops focally at the intervertebral
      junctions as a result of a complex process of disc degeneration, facet
      arthropathy, ligamentum flavum hypertrophy, spondylosis, and sometimes
      spondylolisthesis. All patients underwent a midline decompressive laminectomy
      with foraminotomies at the affected levels, and discectomy was performed in
      persons with lumbar disc hernia. Average age was 71.15 +/- 5.09 (65-80); 50% (16)
      were women, and 50% (16) were men. The most frequent symptoms were pain (96.9%)
      and neurological claudication (90.6%). The average preoperative duration of the
      symptoms was 139.87 +/- 115.03 weeks. The most frequent neurological symptoms
      were reflex disturbances (62.5%), Laseques's sign (SLR) (+)(53%), and motor
      deficit (50%). The anteroposterior diameter of the spinal canal was less than
      11.5 mm in 71.9% of the cases. In 62.5% of the patients, partial recovery was
      observed in the short term; 68.8% of the patients underwent laminectomy. Of
      those, 87.5% had total and 12.5% had partial laminectomies. In addition to
      laminectomy, discectomy was performed in 31.3% of the patients. Total laminectomy
      was more likely to be performed on patients older than 65 years, because the
      anteroposterior diameter was more likely to be below 11.5 mm in this cohort of
      patients. In lumbar stenosis, surgical treatment-decompression-is an effective
      method. Surgery has been demonstrated to be effective even in patients over the
      age of 75 years.

PMID- 17460176
TI  - Comparison of Lipoprotein(a) levels between elderly and middle-aged men with
      coronary artery disease.
AB  - Lipoprotein(a) [Lp(a)] is known to be a risk factor for atherosclerotic disease
      in middle-aged men, but the role of Lp(a) in women and in the elderly is less
      clear. In most studies, excess Lp(a) is not associated with increased risk for
      persons >65 years of age. This study examined the strength of association of a
      number of risk factors to coronary artery disease (CAD) in groups of men <65
      years (n = 108) and >65 of age (n = 66) with angiographically documented
      significant narrowing of coronary arteries. Serum Lp(a) concentrations were
      determined; elevated Lp(a) is positively associated with CAD for men <65 years
      (adjusted OR: 2.45, P <0.05) but not for men >65 of age (adjusted OR: 0.56, P =
      NS). For middle-aged men, elevated Lp(a) appears to be an independent risk factor
      for premature CAD, and the importance of Lp(a) as a risk factor appears to
      decrease with age. These data suggest that the utility of Lp(a) lipoprotein
      levels in predicting the risk of CAD in older men is limited. Factors, such as
      age; sex; levels of total cholesterol, low-density lipoprotein (LDL) cholesterol,
      and triglycerides; carotid-wall thickness; smoking status; the presence or
      absence of diabetes and systolic and diastolic hypertension; body mass index
      (BMI); and other traditional risk factors, must be evaluated together to
      determine the risk of CAD for the entire population.

PMID- 17460177
TI  - Chitotriosidase levels in healthy elderly subjects.
AB  - Chitotriosidase (CHIT) belongs to the family of glycosylhydrolases and is highly
      homologous to chitinases from lower organisms. The enzyme CHIT is of interest for
      clinical reasons, because it is selectively expressed in chronically activated
      tissue macrophages. In most ethnic groups, approximately 6% of all individuals
      are homozygous for CHIT deficiency. Pathological tissue macrophages in several
      disease conditions massively express CHIT. A shared feature of such cells in the
      different conditions is the accumulation of lipid material in the lysosomal
      apparatus. Serum CHIT activity is significantly increased in individuals
      suffering from atherosclerosis disease and is related to the severity of the
      atherosclerotic lesion, suggesting a possible role as atherosclerotic extent
      marker. Our objective is to determine the levels of serum CHIT activity in
      healthy elderly subjects. Healthy 90 (between 65-94 years old) elderly people and
      69 (between 20-44 years old) young people were chosen. Serum CHIT enzymatic
      activity was determined with the flurometric enzyme activity assay using
      artificial 4-MU substrate. We found CHIT activity 270 +/- 21 (nmol/mL/h) (values
      are mean +/- SD) in elderly people and 136 +/- 17 in young people. There are
      statistical differences between elderly and young subjects.

PMID- 17460178
TI  - Genetic variation in the interleukin-10 gene promoter and risk of coronary and
      cerebrovascular events: the PROSPER study.
AB  - Proinflammatory cytokines, like interleukin-6 (IL-6) and tumor necrosis factor
      alpha (TNF-alpha), are implicated in the development of atherosclerosis. The role
      of anti-inflammatory cytokines, like IL-10, is largely unknown. We investigated
      the association of four single nucleotide polymorphisms (SNPs) in the promoter
      region of the IL-10 gene (4259AG, -1082GA, -592CA, and -2849GA), with coronary
      and cerebrovascular disease in participants of the PROspective Study of
      Pravastatin in the Elderly at Risk (PROSPER) trial. All associations were
      assessed with Cox proportional hazards models adjusted for sex, age, pravastatin
      use, and country. Haplotype analysis of the four SNPs showed a significant
      association between haplotype 4 (containing the -592A variant allele) and risk of
      coronary events (P = 0.019). Moreover, analysis of separate SNPs found a
      significant association between -2849AA carriers with incident stroke (HR (95%CI)
      1.50 (1.04-2.17), P value = 0.02). Our study suggests that not only
      proinflammatory processes contribute to atherosclerosis, but that also anti
      inflammatory cytokines may play an important role.

PMID- 17460179
TI  - Antioxidant enzymes and diabetic retinopathy.
AB  - The aim of this study was to discuss the serum copper (Cu), zinc (Zn), nitric
      oxide (NO), glutathione (GSH), advanced oxidation protein products (AOPP) levels,
      and superoxide dismutase (SOD) activities with diabetic retinopathy severity.
      Twenty-five patients with proliferative diabetic retinopathy (PDR group 1), 25
      patients with nonproliferative diabetic retinopathy (NPDR group 2), and 25
      nondiabetic controls (control group) were included in the study. Patients who had
      macrovascular complications of diabetes (coronary arterial disease, periferic
      vascular disease) were excluded. The major finding of our study was that we did
      not observe any differences between group 1 and 2, which we aimed to discuss the
      severity of diabetic retinopathy. As the levels of SOD and Zn were not different
      between the groups, statistically significant differences were observed for GSH,
      NO, and Cu levels when compared to control group. AOPP levels were statistically
      increased in group 1 compared to control group. It can be suggested that
      hyperglycemia in DM is associated with accelerated nonenzymatic glycation and
      oxidative stress.

PMID- 17460180
TI  - Pseudoexfoliation syndrome and trace elements.
AB  - To investigate the role of zinc and copper in the development of
      pseudoexfoliation (PSX) syndrome, 34 cataract patients with PSX syndrome and 27
      cataract patients without PSX syndrome were included in the study and groups were
      matched for age and gender. During the cataract surgery, lenses were obtained
      intraoperatively, frozen under liquid nitrogen, and kept at -70 degrees C until
      processing. Zinc and copper concentrations were measured by atomic absorption
      spectrophotometric method after the homogenization (acid hydrolysis) of dried
      lenses. The mean concentration of zinc in the lens from patients with PSX (20.33
      +/- 8.76 microg/g tissue; range 11.04-42.94 microg/g tissue) was significantly
      lower than that measured in the lens of patients without PSX (28.88 +/- 15.32
      microg/g tissue; range 12.02-64.32 microg/g tissue) (P < 0.05). The mean
      concentration of copper in the lens from patients with PSX (29.51 +/- 10.05
      microg/g tissue; range 12.69-59.71 microg/g tissue) and in the lens of patients
      without PSX (39.72 +/- 25.64 microg/g tissue; range 12.38-92.14 microg/g tissue)
      was not statistically different. The decreased content of zinc could increase
      oxidative stress. The results support the role of oxidative stress in the
      development of PSX in cataract patients.

PMID- 17460181
TI  - The importance of serum lipids in exudative diabetic macular edema in type 2
      diabetic patients.
AB  - To evaluate the relationship between serum lipid levels and exudative diabetic
      maculopathy in patients with nonproliferative diabetic retinopathy, 27 patients
      with exudative diabetic macular edema were included in group A and 27 patients
      without exudative diabetic macular edema were included in group B. All 54
      patients have nonproliferative diabetic retinopathy. Blood cholesterol,
      triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein
      (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, hemoglobin
      A1c (HbA1c), and hemoglobin levels were measured in patients in group A and group
      B. The mean concentration of cholesterol in group A (224.30 +/- 49.49 mg/dL), in
      group B (197.78 +/- 41.49 mg/dL); triglyceride in group A (199.11 +/- 90.51
      mg/dL), in group B (160.78 +/- 65.30 mg/dL); HDL in group A (43.48 +/- 10.62
      mmol/L), in group B (42.37 +/- 10.92 mmol/L); LDL in group A (150.59 +/- 43.96
      mg/dL), in group B (124.37 +/- 40.28 mg/dL); VLDL in group A (40.52 +/- 16.54
      mg/dL), in group B (37.89 +/- 23.70 mg/dL); HbA1c in group A (9.62 +/- 2.50), in
      group B (7.36 +/- 1.62 g/dL); and hemoglobin in group A (13.46 +/- 1.6 g/dL), in
      group B (13.90 +/- 1.77 g/dL). Serum cholesterol (P = 0.38), LDL (P = 0.026), and
      HbA1c (P = 0.000) levels were different between the two groups. Triglyceride,
      HDL, VLDL, and hemoglobin levels were not different between the two groups. We
      must consider regulation of high blood sugar and elevated total serum cholesterol
      or LDL levels in patients with macular edema and high hard exudates.

PMID- 17460182
TI  - Age-related paraoxonase activity changes in Turkish population.
AB  - Paraoxonase1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme capable
      of hydrolyzing diverse substrates from organophosphate (OP) toxins to oxidized
      phospholipids. As such, it has been linked with both the prevention of OP
      poisoning and inhibition of atherosclerosis initiated by oxidatively modified low
      density lipoprotein (LDL). The aim of this study was to investigate, with aging,
      the activity of PON1 associated with HDL and partially responsible for its
      antiatherogenic activity. The study involved 187 individuals (67 males and 120
      females) divided into three groups according to their ages, young (n = 49; 20-44
      years, mean age = 30.12 +/- 6.6 years), middle aged (n = 25; 45-64 years, mean
      age = 52 +/- 5.6 years), and elderly subjects (n = 113; 65-95 years, mean age =
      78.94 +/- 6.2 years). Interestingly, serum total cholesterol and LDL-cholesterol
      levels significantly decreased with age (P < 0.05). The elderly aged group had
      also significantly lower body mass index than the middle aged group (P < 0.05).
      Serum paraoxonase activity and HDL cholesterol levels remained unchanged with
      age. The prevalence of phenotype AA, AB, and BB in our subjects' group was 40.6%,
      45.9%, and 13.5%, respectively.

PMID- 17460183
TI  - Evaluation of measurement uncertainty of glucose in clinical chemistry.
AB  - The definition of the uncertainty of measurement used in the International
      Vocabulary of Basic and General Terms in Metrology (VIM) is a parameter
      associated with the result of a measurement, which characterizes the dispersion
      of the values that could reasonably be attributed to the measurand. Uncertainty
      of measurement comprises many components. In addition to every parameter, the
      measurement uncertainty is that a value should be given by all institutions that
      have been accredited. This value shows reliability of the measurement. GUM,
      published by NIST, contains uncertainty directions. Eurachem/CITAC Guide CG4 was
      also published by Eurachem/CITAC Working Group in the year 2000. Both of them
      offer a mathematical model, for uncertainty can be calculated. There are two
      types of uncertainty in measurement. Type A is the evaluation of uncertainty
      through the statistical analysis and type B is the evaluation of uncertainty
      through other means, for example, certificate reference material. Eurachem Guide
      uses four types of distribution functions: (1) rectangular distribution that
      gives limits without specifying a level of confidence (u(x)=a/ radical3) to a
      certificate; (2) triangular distribution that values near to the same point
      (u(x)=a/ radical6); (3) normal distribution in which an uncertainty is given in
      the form of a standard deviation s, a relative standard deviation s/ radicaln, or
      a coefficient of variance CV% without specifying the distribution (a =
      certificate value, u = standard uncertainty); and (4) confidence interval.

PMID- 17460184
TI  - Mitochondrial DNA mutations and aging.
AB  - Mitochondria have been hypothesized to play a role in both aging and
      neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's
      disease. Many studies have shown the accumulation of mitochondrial DNA (mtDNA)
      mutations in post-mitotic tissues and more recent data have shown this also to be
      a feature of aging mitotic tissues. Much of this data has been correlative, until
      recently with the development of polymerase gamma deficient mice which accumulate
      high levels of mtDNA mutations and show a premature aging phenotype, that a more
      causative role has been proposed. This article focuses on recent developments in
      aging research into the role that mtDNA mutations play in the aging process.

PMID- 17460185
TI  - Mitochondrial DNA-deficient models and aging.
AB  - Human mitochondrial DNA (mtDNA) encodes 13 subunits of oxidative phosphorylation
      (OXPHOS) enzyme complexes I, III, IV, and V except complex II. MtDNA is more
      sensitive to oxidative damage than nuclear DNA. MtDNA defects are involved in
      many pathologies including aging. Several mtDNA-deficient cell culture, yeast,
      and animal models were generated to study the role of mtDNA in many physiological
      processes. Ethidium bromide (EB), an agent that is known to inhibit mtDNA
      replication with a negligible effect on nuclear DNA, is generally used to
      generate mtDNA-deficient models. The antibiotics chloramphenicol and doxycycline,
      which were known to inhibit mitochondrial translation, were also used to generate
      the same phenotype. Cultured mtDNA-deficient cells need uridine and pyruvate to
      survive. At the organismal level, uridine can be supplemented, but pyruvate
      supplementation can cause a worser phenotype because of lactic acidosis. In C.
      elegans, EB, when used during larval development, increases life span, but
      decreases, when used after the beginning of adult stage. This should be kept in
      mind since mitochondria-related genes are generally detected in genome-wide
      screening studies for longevity. We believe that conditional knockout studies
      need to be carried out for these genes after reaching adulthood. MtDNA mutator
      mouse did not show an increase of free radical production. Therefore, the
      downstream phenomena to mtDNA defects are likely ineffective pyrimidine synthesis
      (dihydroorotate dehydrogenase, DHODH, needs a functional respiratory chain) and
      excess NADH (decreased NAD pool) in addition to free radicals.

PMID- 17460186
TI  - Mitochondrial DNA alterations in aging.
AB  - During the aging process, the increase of mitochondrial DNA (mtDNA) alterations
      has been reported. In this study, we investigated deletions/insertions in the
      approximately 2.4-kb region (from 14680 to 578 bp) of mtDNA covering D-loop
      region. A total of 96 individuals (ages between 20 and 94 years) were screened in
      this study. Genomic DNA was purified from whole blood samples. The 2.4-kb region
      of mtDNA was amplified with PCR and visualized by agarose gel electrophoresis.
      The sequence of the amplicon was confirmed in one sample by sequencing. We
      detected mtDNA deletions in only two cases (ages 26 and 30 years) at this
      resolution. As a result, there is no increase in the major deletions/insertions
      in the analyzed mtDNA region with aging. Complete sequencing of this region is
      needed to detect any age-dependent changes.

PMID- 17460187
TI  - Alterations to nuclear architecture and genome behavior in senescent cells.
AB  - The organization of the genome within interphase nuclei, and how it interacts
      with nuclear structures is important for the regulation of nuclear functions.
      Many of the studies researching the importance of genome organization and nuclear
      structure are performed in young, proliferating, and often transformed cells.
      These studies do not reveal anything about the nucleus or genome in
      nonproliferating cells, which may be relevant for the regulation of both
      proliferation and replicative senescence. Here, we provide an overview of what is
      known about the genome and nuclear structure in senescent cells. We review the
      evidence that nuclear structures, such as the nuclear lamina, nucleoli, the
      nuclear matrix, nuclear bodies (such as promyelocytic leukemia bodies), and
      nuclear morphology all become altered within growth-arrested or senescent cells.
      Specific alterations to the genome in senescent cells, as compared to young
      proliferating cells, are described, including aneuploidy, chromatin
      modifications, chromosome positioning, relocation of heterochromatin, and changes
      to telomeres.

PMID- 17460188
TI  - PGC-1alpha-induced mitochondrial alterations in 3T3 fibroblast cells.
AB  - Peroxisome proliferation activator receptor (PPAR) gamma-coactivator 1alpha (PGC
      1alpha), a transcription coactivator, functions as a master regulator of a wide
      array of metabolic and physiological processes and is an essential factor in the
      process of mitochondrial biogenesis. Transfection of NIH 3T3 fibroblasts with a
      mouse cDNA for PGC-1alpha led to the induction of markers of mitochondrial
      biogenesis, that is, mitochondrial transcription factor A (mtTFA), cytochrome c,
      and mitochondrial DNA (mtDNA). Mitochondrial biogenesis-associated net protein
      synthesis appears to be accomplished by a reduction in the rate of mitochondrial
      protein degradation with little or no change in the rate of protein synthesis.
      Overexpression of PGC-1alpha did not adversely affect cellular proliferation.
      Cellular ATP levels were increased in the transfected cells and they were more
      resistant to oxidative stress than the control nontransfected 3T3 cells. This
      resistance to oxidative stress was manifested by both an improved viability and
      the maintenance of mitochondrial membrane potential in the transfected cells when
      exposed to t-butyl hydroperoxide (t-BOOH). It therefore appears that PGC-1alpha
      overexpression stimulates mitochondrial biogenesis in 3T3 cells making them more
      resistant to oxidative stressors.

PMID- 17460189
TI  - Proteasome and photoaging: the effects of UV irradiation.
AB  - Cellular aging is characterized by the accumulation of oxidatively modified
      proteins that result, at least in part, from impaired degradation of abnormal
      proteins. The proteasome is the major intracellular proteolytic system implicated
      in the removal of abnormal and oxidized proteins. In human epidermal cells,
      previous studies have evidenced that proteasome function is decreased during
      aging as well as upon UV irradiation, which is the main component of photoaging.
      The age-related decline of proteasome activity has been reported to be due to
      either or both decreased proteasome subunits expression and content, inactivation
      upon alteration of proteasome subunits, and accumulation of endogenous
      inhibitors, such as highly oxidized and cross-linked proteins. To gain further
      insight in the mechanisms that might be implicated in the decreased activity of
      the proteasome upon photoaging, purified 20S human proteasome has been exposed to
      UVA- and UVB-irradiation. The effect of such an irradiation on proteasome
      peptidase activities has been monitored and shown to promote a stimulation or an
      inhibition of the peptidase activities depending on whether the proteasome is
      under its latent or a nonphysiological active form. Analysis of the patterns of
      proteasome subunits by 2D gel electrophoresis has revealed modification for
      several subunits for UV-irradiated proteasome only in its irreversibly activated
      form, compared with nonirradiated and irradiated latent forms, indicating that
      the 20S proteasome is rather resistant to UV irradiation.

PMID- 17460190
TI  - Proteome alterations in rat mitochondria caused by aging.
AB  - Analysis of the protein profile of mitochondria and its age-dependent variation
      is a promising approach to unravel mechanisms involved in aging and age-related
      diseases. Our studies focus on the mammalian mitochondrial membrane proteome,
      especially of the inner mitochondrial membrane with the respiratory chain
      complexes and other proteins possibly involved in life-span control and aging.
      Variations of the mitochondrial proteome during aging, with the emphasis on the
      abundance, composition, structure, and activity of membrane proteins, are
      examined in various rat tissues by native polyacrylamide gel electrophoresis
      techniques in combination with MALDI-TOF mass spectrometry. In rat brain, age
      modulated differences in the abundance of various mitochondrial and
      nonmitochondrial proteins, such as Na,K-ATPase, HSP60, mitochondrial aconitase-2,
      V-type ATPase, MF(o)F(1) ATP synthase, and the OXPHOS complexes I-IV are
      detected. During aging, a decrease in the amount of intact MF(o)F(1) ATP synthase
      occurs in the cortex. As analytical technique, native PAGE separates not only
      individual proteins but also multi-subunit (membrane) proteins, (membrane)
      protein supercomplexes as well as interacting proteins in their native state. It
      reveals the occurrence and architecture of supramolecular assemblies of proteins.
      The age-related alterations in the oligomerization of the MF(o)F(1) ATP synthase
      observed by us in rat cortex might be one clue for understanding the link between
      respiration and longevity. Also, the abundance of OXPHOS supercomplexes, that is,
      the natural assemblies of the respiratory complexes I, III, and IV into
      supramolecular stoichiometric entities, such as I(1)III(2)IV(0-4), can differ
      between young and aged cortex tissue. Age-related changes in the supramolecular
      architecture of OXPHOS complexes might explain alterations in ROS production
      during aging.

PMID- 17460191
TI  - The role of the MORF/MRG family of genes in cell growth, differentiation, DNA
      repair, and thereby aging.
AB  - The discovery that replicative cellular senescence is a dominant phenotype over
      immortality led to the discovery that there are at least four unique genetic
      subgroups of immortal cell lines that use distinct mechanistic pathways to evade
      cell cycle exit. Study of one of these genetic complementation groups
      demonstrated that one gene, MORF4, possessed the ability to induce senescence in
      group B cell lines. The MRG family of genes, of which MORF4 is a member, has
      since proven important for cellular aging, proliferation, positive and negative
      transcriptional regulation, and DNA damage repair. MRG15, the evolutionary
      ancestor of the family, is highly conserved in yeast, C. elegans, drosophila,
      plants, and mammals and has been implicated in chromatin remodeling in these
      species. Our proteomics studies have found that MRG15 is unique among mammalian
      genes in that it associates with both histone deacetylases and histone acetyl
      transferase complexes, and thus potentially plays a role in both transcriptional
      silencing and activation. Its knockout in mice is embryonic lethal, resulting in
      improper organogenesis, as well as cell proliferation and DNA damage repair
      defects. Future study of these genes will help clarify the role of chromatin
      remodeling in aging, cellular proliferation, and DNA damage repair.

PMID- 17460192
TI  - Involvement of mortalin in cellular senescence from the perspective of its
      mitochondrial import, chaperone, and oxidative stress management functions.
AB  - Mortalin (mtHSP70/GRP75) is a heat uninducible member of hsp70 family of
      proteins. Some of the established features of mortalin include its various
      subcellular sites, multiple binding partners, and differential subcellular
      distribution in normal and immortal cells. Overexpression of mortalin leads to
      extended life span in nematode and normal human cells. On the other hand, it
      serves as a major target for oxidation and was shown to be involved in old age
      pathologies including Parkinson's and Alzheimer's disease. Since mortalin
      interacts with many proteins, its modifications in response to stress and damage
      caused by intracellular oxidation are likely to generate pleiotropic effects. For
      example, (a) inefficient import of mitochondrial proteins by mortalin-Tim
      complexes may result into inefficient mitochondrial genesis, energy generation,
      and functional decline and (b) inefficient chaperoning of proteins can result
      into a garbage catastrophe.

PMID- 17460193
TI  - CARF binds to three members (ARF, p53, and HDM2) of the p53 tumor-suppressor
      pathway.
AB  - The INK4a locus (chromosome 9p21) encodes two structurally distinct tumor
      suppressor proteins, p16(INK4a) and the alternative reading frame protein, ARF
      (p19(ARF) in mouse and p14(ARF) in human). Each of these proteins has a major
      role in cell cycle control and senescence pathways. We originally identified a
      novel collaborator of ARF, CARF, from a two-hybrid interactive screen using
      p19(ARF) as bait and found that CARF interacts with ARF in the perinucleolar
      region and activates p53 function. In the absence of ARF, it interacts with p53
      directly leading to ARF-independent enhancement of p53 function and in turn
      undergoes a negative feedback regulation. Very recently, we found that CARF
      interacts with HDM2 and undergoes degradation by an HDM2-dependent proteasome
      pathway. CARF may exert a vital control on p53-HDM2-p21(WAF1) pathway that is
      central to the cell cycle control, senescence, and DNA damage response of human
      cells.

PMID- 17460194
TI  - Knocking down p53 with siRNA does not affect the overexpression of p21WAF-1 after
      exposure of IMR-90 hTERT fibroblasts to a sublethal concentration of H2O2 leading
      to premature senescence.
AB  - Premature senescence of IMR-90 human diploid fibroblasts (HDFs) expressing
      telomerase was induced by exposure to sublethal concentration of H(2)O(2), with
      appearance of several biomarkers of cellular senescence like enlarged cell shape,
      senescence-associated beta-galactosidase (SA ss-gal) activity, and cell cycle
      arrest. The induction of stress-induced premature senescence (SIPS) was
      associated with a transient increase in DNA-binding activity of p53 and an
      increased expression of p21(WAF-1). p53 small interferent RNA (siRNA) affected
      the basal level of p21(WAF-1) mRNA but did not affect the overexpression of
      p21(WAF-1) after stress. This siRNA approach confirms previous results obtained
      with other methods.

PMID- 17460195
TI  - Beta-galactosidase activity as a biomarker of replicative senescence during the
      course of human fibroblast cultures.
AB  - It has been called into question whether the commonly used beta-galactosidase
      staining is a reliable biomarker of cellular senescence because induction of beta
      galactosidase activity also occurs independently of senescence. Here, we tested
      whether cytochemically detectable beta-galactosidase activity is reproducible and
      reflects the rate of cellular aging in vitro. Therefore, we serially cultured
      fibroblasts from 12 different donors and stained the cells for beta-galactosidase
      at pH 6 until the onset of the permanent growth arrest of the individual
      cultures. All fibroblast strains displayed a high replicative capacity with a
      similar growth pattern during the exponential growth phase and a very high
      interbiopsy variability in the onset of decreased mitotic activity and in the
      onset of growth arrest. Correspondingly, beta-galactosidase activity was low
      during the exponential growth phase, with an individually defined significant
      increase in activity when the growth speed of the culture decreased. The increase
      in beta-galactosidase activity was a better predictor for the onset of the
      decreased growth speed than the chronological life span of the culture expressed
      in population doublings. Within the phase of decreased mitotic activity, we
      observed a high fluctuation in the percentage of positively stained fibroblasts.
      Thus, our results support beta-galactosidase activity as a reliable biomarker for
      the course of replicative senescence, if used under defined standardized
      conditions.

PMID- 17460196
TI  - A dual role of p21 in stem cell aging.
AB  - A decline in adult stem cell function occurs during aging, likely contributing to
      the decline in organ homeostasis and regeneration with age. An emerging field in
      aging research is to analyze molecular pathways limiting adult stem cell function
      in response to macromolecular damage accumulation during aging. Current data
      suggest that the p21 cell cycle inhibitor has a dual role in stem cell aging: On
      one hand, p21 protects adult stem cells from acute genotoxic stress by preventing
      inappropriate cycling of acutely damaged stem cells. On the other hand, p21
      activation impairs stem cell function and survival of aging telomere
      dysfunctional mice indicating that p21 checkpoint function is disadvantageous in
      the context of chronic and persistent damage, which accumulates during aging.
      This article focuses on these dual roles of p21 in aging stem cells.

PMID- 17460197
TI  - Age-dependent effects on functional aspects in human satellite cells.
AB  - In humans aging is a complex process that determines many physical and metabolic
      alterations correlated to the accumulation of oxidative damage in different
      tissues. Sarcopenia is an age-related nonpathological condition that includes a
      progressive loss of mass and strength in skeletal muscle, associated with a
      decline in the fibers' functional capability. This condition could be correlated
      to abnormal reactive oxygen species (ROS) accumulation with consequent fiber
      oxidative damage. This complex situation is not only evident in mature muscle
      fibers but also in muscle resident satellite cells (involved in fiber damage
      repairing) in which some functional parameters, at least for that concerns the
      Ca(2+) homeostasis, seem to be modified. In fact, our data show that there is an
      age-dependent increase of lipid peroxidation, in cultured myotubes
      (differentiated and fused satellite cells) after 7 days of in vitro
      differentiation. In these substrates also the capacity of these cells to produce
      Ca(2+) transient in response to various stimuli (ATP, caffeine, nicotine, KCl)
      is, sometimes, drastically modified. In particular, the presence of an age
      dependent defective status of excitation-contraction (EC) coupling apparatus is
      supported by a single cell Ca(2+) analysis obtained from myotubes (derived from
      aged muscles) in the presence of 40 mM caffeine or 40 mM KCl. The alkaloid
      presence induces a complete emptying of ryanodine-dependent calcium stores
      indicating a probable integrity both of SR-terminal cisternae and/or the specific
      Ca(2+) channel known as RyR1. However, if a sarcolemmal depolarization is induced
      by the addition of 40 mM KCl in the experimental medium then Ca(2+) release RyR1
      dependent can be observed only if Ca(2+) is present in the experimental solution.
      These results suggest that the EC uncoupling status could be due to the
      alteration of the interaction between RyR and DHPR. The two receptors are present
      and functionally active in myotubes from aged donors but they are probably still
      not in the right localization. These results suggest that during donor's life the
      satellite cells undergo an aging process similar to the one observed in skeletal
      muscle tissue, even if they are in a quiescence status for most of the time.

PMID- 17460198
TI  - Vascular smooth muscle and endothelial functions in aging.
AB  - Aging is one of the main risk factors for the development of atherosclerosis and,
      therefore, for coronary artery disease. Age-associated remodeling of the vascular
      wall includes luminal enlargement, intimal and medial thickening, and increased
      vascular stiffness. As aging occurs, smooth muscle cells (SMCs) progressively
      migrate from the tunica media and accumulate into the tunica intima. Aging also
      associates with changes of SMC proliferative and apoptotic behavior and response
      to growth factors, such as transforming growth factor-beta1. Aging induces a
      reduction in the density of the alpha-subunit of Ca(2+)-activated K(+) channels
      in coronary smooth muscle and increases the response to endothelial constrictor
      factors and K(+). Accordingly, we have recently shown that the vasodilatory
      effect of male sex hormone testosterone, which is mediated through large
      conductance Ca(2+)-activated K(+) channel opening action, decreases with age.
      Apart from age-associated remodeling of the vascular wall, endothelial function
      declines with age. This is most obvious from the attenuation of endothelium
      dependent dilator responses, which is a consequence of the alteration in the
      expression and/or activity of the endothelial nitric oxide (NO) synthase,
      upregulation of the inducible NO synthase, and increased formation of reactive
      oxygen species. In fact, in the course of aging, there is an alteration in the
      equilibrium between relaxing and contracting factors released by the endothelium.
      Hence, there is a progressive reduction in the participation of NO and
      endothelium-derived hyperpolarizing factor (EDHF) associated with increased
      participation of oxygen-derived free radicals and cyclooxygenase-derived
      prostanoids. Also, the endothelin-1 and angiotensin II pathways may play a role
      in age-related endothelial dysfunction. Aging is also associated with a reduction
      in the regenerative capacity of the endothelium and endothelial senescence, which
      is characterized by an increased rate of endothelial cell apoptosis. Thus, aging
      elicits several changes in the vascular endothelium gradually altering its
      phenotype from an anti- to a proatherosclerotic one. In conclusion, it becomes
      increasingly evident that the blood vessel structural and functional
      disturbances, which characterize vascular aging, make a major contribution to
      aging-related target organ damage. The use of drugs, including antioxidant
      therapy, lipid-lowering drugs, and estrogens, seems to be promising.

PMID- 17460199
TI  - The differentiation-associated linker histone, H1.0, during the in vitro aging
      and senescence of human diploid fibroblasts.
AB  - There are numerous similarities between aging/senescence and differentiation. One
      key similarity is that in both biological processes chromatin remodeling events
      occur. It is now known that during both processes there is a reorganization of eu
      and heterochromatic domains and an increase in heterochromatin, known as
      heterochromatinization. Previous work of more than two decades has shown that the
      replacement H1 linker histone subtype, H1.0, accumulates during terminal
      differentiation in numerous cell/tissue systems. However, work with this
      differentiation-associated H1 subtype in aging cell systems has only recently
      been accomplished. In this article, we outline the cumulative results from our
      investigations of H1.0 protein and mRNA levels in the in vitro aging cell system
      of human diploid fibroblasts (HDFs) and discuss the potential rationale of why
      this particular subtype was found to accumulate during both these processes.

PMID- 17460200
TI  - Quantum dot-based mortalin staining as a visual assay for detection of induced
      senescence in cancer cells.
AB  - Quantum dots (QDs) are fluorescent nanocrystals that are emerging as fine
      alternatives to the conventional organic dyes. They have several advantages
      including greater photostability and a wider range of excitation-emission
      wavelengths. By using mortalin staining as a model, we initially demonstrated
      that the QDs are more stable and provide better resolution in protein imaging in
      fixed cells. With the help of an internalizing antibody, we generated
      internalizing QD (i-QD) and demonstrated its inertness to cell replication,
      structure, and viability. Based on the superior resolution, stability and
      inertness, we propose the use of QD staining of mortalin as a cell-based visual
      assay to screen for senescence-inducing drugs, proteins, and siRNAs.

PMID- 17460201
TI  - Markers of oxidative stress in erythrocytes during aging in humans.
AB  - The correlation between antioxidant capacity and oxidative damage during aging
      has been reported in several tissues in different species; however, data on
      changes of oxidative stress markers in plasma and erythrocytes of healthy
      populations during aging are few and sometimes contradictory. Since antioxidant
      capacity of the plasma is related to dietary intake of antioxidants, it is
      important to study the correlation between antioxidant capacity of the plasma and
      markers of oxidative stress in different populations. In the present study we
      report the age-dependent alteration in erythrocyte malondialdehyde (MDA),
      intracellular-reduced glutathione (GSH), and membrane sulphydryl (SH) groups in
      the Indian population and also correlate these parameters with total plasma
      antioxidant potential. We show an age-dependent increase in erythrocyte MDA level
      and a decrease in GSH and membrane -SH group concentration. The alterations in
      these parameters correlated significantly with total antioxidant capacity of the
      plasma. We observe a higher oxidative stress in the Indian population compared to
      values reported for European subjects emphasizing the need to establish age
      dependent reference values for oxidative stress markers in different populations
      and in studies involving their role in different disease conditions.

PMID- 17460202
TI  - Methionine sulfoxide reduction and the aging process.
AB  - Aging has been described for multicellular and asymmetrically dividing organisms,
      but the mechanisms are poorly understood. Oxidation of proteins is considered to
      be one of the major factors that leads to aging. Oxidative damage to proteins
      results in the oxidation of certain amino acid residues, among which oxidation of
      sulfur-containing amino acids, methionine and cysteine, is notable because of the
      susceptibility of these residues to damage, and occurrence of repair mechanisms.
      Methionine sulfoxide reductases, MsrA and MsrB, are thioredoxin-dependent
      oxidoreductases that reduce oxidized forms of methionine, methionine sulfoxides,
      in a stereospecific manner. These enzymes are present in all cell types and have
      shown to be regulating life spans in mammals, insects, and yeast. Here, their
      roles in modulating yeast life span are discussed.

PMID- 17460203
TI  - Activation of pericentromeric and telomeric heterochromatin in cultured
      lymphocytes from old individuals.
AB  - The functional characteristics of chromosomes (level of total heterochromatin,
      chromosome instability, and sister chromatid exchanges [SCEs]) were studied in
      cultured lymphocytes derived from 80- to 91-year-old and 18- to 30-year-old
      (control group) individuals under the single and combined effect of CoCl(2) and
      bioregulator Livagen. The results obtained showed that chromosome
      heterochromatinization (condensation of eu- and heterochromatin regions) had
      progressively increased with aging and led to inactivation of a number of once
      functioning "active genes." The peptide bioregulator Livagen could induce
      reactivation (deheterochromatinization) of chromatin to modify
      heterochromatinized chromosomal regions in cultured lymphocytes of aged
      individuals. Our results indicated that metal ions (CoCl(2)) caused a significant
      increase in the level of chromosomal aberrations in old donors in comparison with
      the control group (P < 0.05). The peptide bioregulator Livagen was effective in
      decreasing the number of changes induced by the CoCl(2) 3.4 +/- 0.6% (control
      group 4.2 +/- 0.7%). Co(2+) ions single and Co(2+) ions in combination with the
      Livagen changed the distribution of SCE over chromosomes: pericentromeric
      heterochromatin was more sensitive to the effect of CoCl(2) (15.4 +/- 1.8% SCE),
      while SCE were mostly registered in telomeric heterochromatin under the combined
      effect of CoCl(2) and Livagen 12.0 +/- 1.2% SCE (control group 4.5 +/- 0.6% and
      2.8 +/- 0.5% SCE, respectively). Thus, we have first demonstrated that Co(2+)
      ions separately and in combination with the bioregulator Livagen have different
      chromosomal target regions as demonstrated by SCE induction,
      deheterochromatinization of precentromeric and telomeric heterochromatin in
      lymphocytes from old individuals.

PMID- 17460204
TI  - Deuteronation and aging.
AB  - Deuterium has one proton and one neutron in its atomic nucleus, but hydrogen has
      only proton. The natural abundance of deuterium is 1 per approximately 6600
      hydrogen atoms. Therefore deuterated water (both HOD + D(2)O [heavy water])
      abundance is 1 per approximately 3300 water molecules. One dissociation product
      of deuterated and heavy water is deuteron (proton + neutron, D(+),
      H(2)OD(+)/D(3)O(+)). Because heavy water has a lower ionization constant than
      water, the D(+)/H(+) ratio is approximately 1/15,000 in biological fluids. O-D
      bond length is shorter than O-H, and D-O-D angle is lesser than H-O-H. Once a
      deuteron exchanges with proton on the water-exposed surface of a macromolecule,
      it can lead to a conformational change and the reverse exchange will be less
      likely. Deuteron bonds are stronger than proton bonds. Therefore an increase of
      deuteronated macromolecules can be expected in due course of time. In order to
      test this hypothesis, we conducted a pilot study and measured the D/H ratio in
      the tails of three Sprague-Dawley rats at different ages (4 weeks, 5 weeks, and
      >1-year old) by elemental analysis coupled with isotope ratio mass spectrometry
      (EA-IRMS) technique. To prevent the effect of daily water consumption, the
      homogenized tails were lyophilized before analysis. The results, as mean of
      several measurements, of 4 weeks, 5 weeks, and >1-year-old rats were per thousand
      94 +/- 9.56, per thousand-101.71 +/- 6.89, per thousand-83.68 +/- 3.46
      delta((2)H) relative to VSMOW, respectively. Although there is a slight increase
      in >1-year-old rat, the difference among the animals was not significant. We
      propose that, before reaching to a final conclusion about the accumulation of
      deuterium with aging, the measurements should be done not in whole tissue samples
      but in purified macromolecules from a larger set of animals.

PMID- 17460205
TI  - Hemodialysis and protein oxidation products.
AB  - The presence of a chronic inflammatory state has also been widely documented in
      end-stage renal disease patients receiving maintenance hemodialysis (HD). It is
      commonly attributed to the constantly renewed activation of circulating
      neutrophils and monocytes following blood passage through dialysis circuits and
      subsequent generation of activated complement components due to contact of plasma
      with bioincompatible membranes and/or transfer of endotoxins from the dialyzate
      to the blood compartment. This conjunction leads to a massive generation of
      reactive oxygen species (ROS), for example, superoxide anion, hydrogen peroxide,
      hydroxyl radical, and chlorinated oxidants, such as hypochlorous acid by
      activated neutrophils. The exquisite vulnerability of proteins to ROS is now well
      documented. Oxidation of amino acid residues, such as tyrosine, leads to the
      formation of dityrosine, protein aggregation, cross-linking, and fragmentation.
      Dityrosine-containing protein cross-linking products in the plasma of dialysis
      patients are named as advanced oxidation protein products (AOPP). In addition,
      advanced glycation end-products (AGE) is a protein carbonyl compound and produced
      by protein-ROS interaction. We investigated both the effect of the renewed
      activation of the immune cells, due to blood-dialyzer interaction over protein
      oxidation products like AOPP and AGE, among chronic renal failure (CRF) patients
      receiving maintenance HD, and choice of dialyzers like high flux or the other
      group on protein oxidation product levels.

PMID- 17460206
TI  - The natural biogerontology portfolio: "defeating aging" as a multi-stage ultra
      grand challenge.
AB  - The early days of biogerontology were blessed with an undiluted forthrightness
      concerning the field's ultimate goals, epitomized by its leaders. Luminaries from
      Pearl to Comfort to Strehler declared the desirability of eliminating aging with
      no more diffidence than that with which today's oncologists aver that they seek a
      cure for cancer. The field's subsequent retreat from this position garnered a
      modicum of political acceptability and public financial support, but all
      biogerontologists agree that this fell, and continues to fall, vastly short of
      the funding that the prospect of even a modest postponement of aging would
      logically justify. The past 20 years' discoveries of life-extending genetic
      manipulations in model organisms have weakened the argument that a policy of
      appeasement of the public's ambivalence about defeating aging is our only option;
      some of the biogerontologists responsible for these advances have espoused views
      of which our intellectual forefathers would be proud, without noticeably harming
      their own careers. With the recent emergence of a detailed, ambitious, but
      practical roadmap for the comprehensive defeat of aging, this process has moved
      further: our natural and most persuasive public stance is, more than ever, to
      reembrace the same unassailable logic that served pioneering biogerontologists
      perfectly well. In particular, we are in a position to explain that the disparate
      strands of contemporary biomedical gerontology are not in conflict, but rather
      that they constitute a portfolio of approaches with a range of potential
      efficacies and degrees of difficulty of implementation, which can save more lives
      together than any can save individually, and all of which thus merit intensive
      pursuit.

PMID- 17460207
TI  - Hormetic prevention of molecular damage during cellular aging of human skin
      fibroblasts and keratinocytes.
AB  - Progressive accumulation of molecular damage is a hallmark of cellular aging,
      which is amenable to intervention and prevention by hormesis through mild stress.
      Our studies have shown that repeated mild heat stress (RMHS) has antiaging
      effects on growth and various other cellular and biochemical characteristics of
      normal human skin fibroblasts undergoing aging in vitro. RMHS at 41 degrees C,
      for 1 h twice a week, increased the basal levels of various chaperones, reduced
      the accumulation of oxidatively and glycoxidatively damaged proteins, stimulated
      proteasomal activities for the degradation of abnormal proteins, improved
      cellular resistance to ethanol, hydrogen peroxide, and UV-B rays, enhanced the
      levels of various antioxidant enzymes, and increased the phosphorylation-mediated
      activities of various stress kinases. RMHS-exposed human fibroblasts are also
      better protected against glucose- and glyoxal-induced growth inhibition and
      apoptosis. We have also observed various hormetic effects of RMHS on normal human
      epidermal keratinocytes, which include increased replicative life span, increased
      proteasomal activity, and enhanced levels of Na/K-ATPase pump. We are also
      testing the above effects of RMHS in combination with potential hormetic
      molecules, such as curcumin, on aging, longevity, and differentiation of human
      cells in culture.

PMID- 17460208
TI  - Beneficial biochemical outcomes of late-onset dietary restriction in rodents.
AB  - Dietary restriction (DR) or caloric restriction (CR) is the well-established
      means to retard aging, leading to prolongation of mean and maximum life span in
      many animal models. We have been interested in the possibility of extending the
      span of health of elderly people rather than increasing longevity, and therefore
      studied the effects of DR/CR initiated late in life in rodent models. We
      restricted food for 2-3.5 months in mice or rats of middle or old ages, which
      would perhaps be equivalent to 50-70 years of age in humans. We found that: (1)
      Potentially harmful altered proteins were reduced in the animals' tissues. (2)
      Extended half-life of protein in aged animals was shortened in mouse hepatocytes,
      suggesting improved protein turnover. (3) Reduced proteasome activity was
      upregulated in rat liver and skeletal muscle. (4) Protein carbonyls were
      decreased in rat liver mitochondria and skeletal muscle cytoplasm, and also
      oxidative DNA damage was reduced in rat liver nucleus, suggesting amelioration of
      oxidative stress. (5) Reduced apo A-IV and C-III metabolism in aged mouse was
      restored, suggesting increase in reduced fatty acid mobilization. (6) The
      carbonyl modification in histones that was paradoxically reduced in aged rat was
      increased to the level of a young animal, suggesting restoration of reduced
      transcription. These findings in rodents suggest a possibility that DR/CR is
      beneficial if applied in middle-aged or early senescent obese people. We argue,
      however, that application of late life DR/CR can be harmful if practiced in
      people who are already eating modestly.

PMID- 17460209
TI  - Adult-limited dietary restriction slows gompertzian aging in Caenorhabditis
      elegans.
AB  - Dietary restriction (DR) delays the onset of age-related deterioration and
      extends the life span in a variety of model organisms. In many species, age
      changes in mortality obey the Gompertz equation, which describes an exponential
      increase with age in age-specific mortality rate. Recently, this model has been
      used in fruitflies and rodents to investigate the mechanism by which DR reduces
      adult mortality. We report that food restriction imposed by axenic culture
      reduces the exponential increase of age-specific mortality of Caenorhabditis
      elegans. Furthermore, the life span appears largely independent of nutritional
      status during development, as shown by shifting worms to different food
      concentrations shortly before adulthood. When DR was exerted after reproduction,
      a smaller reduction in Gompertzian aging was seen. Thus, the demographic changes
      exerted by DR in C. elegans resemble those seen in rats, yet are different to
      those seen in Drosophila and mice.

PMID- 17460210
TI  - Prior chronic in vivo glucocorticoid excess leads to an anabolic phenotype and an
      extension of cellular life span of skin fibroblasts in vitro.
AB  - Intense stress can be detrimental for tissue homeostasis and accelerates aging.
      On the other hand, repeated mild stresses can have beneficial and even life
      prolonging effects. Hypersecretion of glucocorticoids (GCs) represents the major
      hormonal response to stress. However, besides its life-sustaining role, GC excess
      can promote a "catabolic" phenotype. Accordingly, we have studied the effect of
      long-lasting exposure to high GC levels in vivo on several parameters of tissue
      homeostasis, as well as cellular senescence, in cells removed from the high-GC
      milieu in vivo and then cultured in vitro. To this end, we have used human skin
      fibroblasts from (a) Cushing's syndrome patients that are characterized by
      chronic endogenous GC excess and (b) patients treated with exogenous GC
      administration. Interestingly, when Cushing's syndrome fibroblasts were cultured
      in vitro under standard conditions they express an "anabolic" phenotype, i.e.,
      they restore their ability for collagen synthesis, secrete reduced levels of
      metalloproteases, and have an increased proliferative capacity and contractility.
      Furthermore, these cells exhibit a significant extension of their proliferative
      life span, while they respond better to exogenous stress by producing
      significantly higher levels of heat-shock protein-70 (HSP70). In addition,
      preliminary results with fibroblasts from patients subjected to chronic exogenous
      GC administration indicate that they express a similar behavior in vitro, at
      least with regard to the restoration of collagen expression. These data suggest
      that prior exposure to elevated GC concentrations is not associated with
      persisting adverse effects on fibroblasts and may also have a beneficial outcome
      in some aspects of cell physiology, including longevity in vitro.

PMID- 17460211
TI  - The role of cellular senescence in Werner syndrome: toward therapeutic
      intervention in human premature aging.
AB  - Werner syndrome (WS) is a premature aging disorder used as a model of normal
      human aging. WS individuals have several characteristics of normal aging, such as
      cataracts, hair graying, and skin aging, but manifest these at an early age.
      Additionally, WS individuals have high levels of inflammatory diseases, such as
      atherosclerosis and type 2 diabetes. The in vivo aging in WS is associated with
      accelerated aging of fibroblasts in culture. The cause of the accelerated
      senescence is not understood, but may be due to the genomic instability that is a
      hallmark of WS. Genome instability results in activation of stress kinases, such
      as p38, and the p38-specific inhibitor SB203580, prevents the accelerated
      senescence seen in WS fibroblasts. However, oxidative damage plays a role, as low
      oxygen conditions and antioxidant treatment revert some of the accelerated
      senescence phenotype. The effects of oxidative stress appear to be suppressible
      by SB203580; however, it does not appear to be transduced by p38. As SB203580 is
      known to inhibit other kinases in addition to p38, this suggests that more than
      one kinase pathway is involved. The recent development of p38 inhibitors with
      different binding properties, specificities, and oral bioavailability, and of new
      potent and selective inhibitors of JNK and MK2, will make it possible to dissect
      the roles of various kinase pathways in the accelerated senescence of WS cells.
      If this accelerated senescence is reflective of WS aging in vivo, these kinase
      inhibitors may well form the basis of antiaging therapies for individuals with
      WS.

PMID- 17460212
TI  - Fruit polyphenols and their effects on neuronal signaling and behavior in
      senescence.
AB  - The onset of age-related neurodegenerative diseases superimposed on a declining
      nervous system could exacerbate the motor and cognitive behavioral deficits that
      normally occur in senescence. It is likely that, in cases of severe deficits in
      memory or motor function, hospitalization and/or custodial care would be a likely
      outcome. This means that unless some way is found to reduce these age-related
      decrements in neuronal function, healthcare costs will continue to rise
      exponentially. Thus, it is extremely important to explore methods to retard or
      reverse the age-related neuronal deficits as well as their subsequent, behavioral
      manifestations. Applying molecular biological approaches to slow aging in the
      human condition may be years away. So it is important to determine what methods
      can be used today to increase healthy aging, forestall the onset of these
      diseases, and create conditions favorable to obtaining a "longevity dividend" in
      both financial and human terms. In this regard, epidemiological studies indicate
      that consumption of diets rich in antioxidants and anti-inflammatory compounds,
      such as those found in fruits and vegetables, may lower the risk of developing
      age-related neurodegenerative diseases, such as Alzheimer's or Parkinson's
      diseases (AD and PD). Research suggests that the polyphenolic compounds found in
      fruits, such as blueberries, may exert their beneficial effects by altering
      stress signaling and neuronal communication, suggesting that interventions may
      exert protection against age-related deficits in cognitive and motor function.
      The purpose of this article is to discuss the benefits of these interventions in
      rodent models and to describe the putative molecular mechanisms involved in their
      benefits.

PMID- 17460213
TI  - Psoralea corylifolia L. inhibits mitochondrial complex I and proteasome
      activities in SH-SY5Y cells.
AB  - The growing interest in alternative medicines, including traditional medicinal
      plants, has caused some health concerns due to poor awareness in the general
      population of the possible side effects from inappropriate practices. Psoralea
      corylifolia L. has been used in Chinese and Indian traditional medicine for the
      treatment of various inflammatory diseases of the skin and to improve vitality.
      Our data show that the extract obtained from the seeds of Psoralea corylifolia L.
      decreased mitochondrial complex I and proteasome activities; and oxidative stress
      might be an early event.

PMID- 17460214
TI  - Improvement of immune cell functions in aged mice treated for five weeks with
      soybean isoflavones.
AB  - Aging is associated with an impaired immune system as well as with a decline of
      several hormones, such as estrogens. Dietary phytoestrogens have been proposed as
      an alternative to hormone replacement therapy. The beneficial action of soybean
      compounds is probably due to isoflavones, whose role as immunomodulators has been
      investigated with increasing interest. The aim of the present work was to study
      whether a 5-week administration of a diet enriched in soybean isoflavones and
      green tea could influence the immune function of mice that were sham-operated or
      ovariectomized. Natural killer activity (NK) and lymphoproliferation in response
      to the mitogens concanavaline A (Con A) and lipopolysaccharide (LPS), were
      studied in peritoneal leukocytes. Both treatments with soybean or green tea plus
      soybean were highly effective in improving these immune parameters with respect
      to control groups. Since the immune system is a marker of health and a predictor
      of longevity, an adequate treatment with isoflavones could be useful in slowing
      down the effects of the aging process through an improvement in the two relevant
      immune functions studied.

PMID- 17460215
TI  - Effects of deleting mitochondrial antioxidant genes on life span.
AB  - Reactive oxygen species (ROS) damage biomolecules, accelerate aging, and shorten
      life span, whereas antioxidant enzymes mitigate these effects. Because
      mitochondria are a primary site of ROS generation and also a primary target of
      ROS attack, they have become a major focus area of aging studies. Here, we
      employed yeast genetics to identify mitochondrial antioxidant genes that are
      important for replicative life span. In our studies, it was found that among the
      known mitochondrial antioxidant genes (TTR1, CCD1, SOD1, GLO4, TRR2, TRX3, CCS1,
      SOD2, GRX5, PRX1), deletion of only three genes, SOD1 (Cu, Zn superoxide
      dismutase), SOD2 (Manganese-containing superoxide dismutase), and CCS1 (Copper
      chaperone), shortened the life span enormously. The life span decreased 40% for
      Deltasod1 mutant, 72% for Deltasod2 mutant, and 50% for Deltaccs1 mutant.
      Deletion of the other genes had little or no effect on life span.

PMID- 17460216
TI  - The effect of intrahippocampal beta amyloid (1-42) peptide injection on oxidant
      and antioxidant status in rat brain.
AB  - In some animal models, cognitive impairment and neurodegenerative disorders that
      mimic Alzheimer's disease (AD) can be reproduced by intracerebral or
      intracerebroventricular administration of peptide (Abeta) beta amyloid. Evidence
      suggests that oxidative stresses are involved in the mechanism of Abeta-induced
      neurotoxicity and AD pathogenesis. Exposure to Abeta increases lipid
      peroxidation, protein oxidation, and the formation of hydrogen peroxide in
      cultured cells. Nitric oxide (NO) has significant physiological roles in the
      central nervous system and also it can be implicated in neurodegenerative
      diseases because of its free radical properties. The purpose of this study is to
      search the effects of intrahippocampal Abeta (1-42) injection on malondialdehyde
      (MDA), glutathione (GSH), and nitrite plus nitrate (NOx) levels in temporal
      cortex and basal forebrain in rats. In this study, male adult Wistar albino rats
      were divided into two groups. Abeta (1-42) peptide (10 mug/2 muL) was
      administered bilaterally as a single injection into the hippocampal fissure by a
      Hamilton microsyringe. Distilled water was administered to the control group by
      using the same procedure. Ten days after the Abeta (1-42) injection, the rats
      were decapitated and brains were rapidly removed. MDA, GSH, and NOx levels were
      analyzed spectrophotometrically in temporal cortex and basal forebrain. MDA
      levels and NOx were increased 10 days after the injection of Abeta (1-42) in
      temporal cortex and basal forebrain, but no statistical significance was found
      compared to control group. However, GSH levels were significantly higher in
      temporal cortex and basal forebrain in the Abeta (1-42)-injected group than the
      control group (P < 0.05). In conclusion, increased levels of GSH in temporal
      cortex and basal forebrain after the intrahippocampal Abeta (1-42) injection show
      that a protective mechanism might develop due to oxidative stress.

PMID- 17460217
TI  - Glyoxal-induced premature senescence in human fibroblasts.
AB  - Mild stress-induced hormesis is an effective strategy to intervene in the aging
      process. Repeated exposure of human skin fibroblasts to 41 degrees C heat shock
      for 1 h twice a week is an example of mild stress that has many hormetic effects,
      including improved resistance to other stressors. We are now developing an
      experimental model system of sugar-induced premature senescence, which can be
      useful to test the hormetic and antiaging effects of other stresses. Our present
      studies show that early-passage human skin fibroblasts treated with 1 mM glyoxal
      for 72 h undergo premature senescence in terms of enlarged cell size, inhibition
      of cell division, slowing down of cell growth, a decrease in the number of DNA
      synthesizing cells, and increased resistance to apoptosis.

PMID- 17460218
TI  - Sugar-induced premature aging and altered differentiation in human epidermal
      keratinocytes.
AB  - Normal human epidermal keratinocytes (NHEK) show both the Hayflick phenomenon and
      differentiation in vitro. The aim of this study was to induce senescence in
      keratinocytes using two sugars, glucose and glyoxal. Induction of senescence in
      early-passage NHEK was characterized by monitoring cell morphology, short-term
      growth characteristics, cell proliferation, and viability assay. In addition,
      apoptosis, senescence-associated (SA) beta-gal activity, proteasomal activity and
      glycation, and glycoxidation of total proteins were determined. Our results show
      that a 3-day treatment with 100 mM glucose or 0.1 mM glyoxal induces in early
      passage NHEK various cellular and biochemical characteristics comparable to those
      observed in serially subcultured late passage NHEK. Furthermore, sugar-treated
      prematurely aged NHEK showed impaired differentiation, as measured by the
      quantification of involucrin. There is preliminary evidence that a preexposure of
      NHEK to mild heat shock (41 degrees C, 1 h, 6 h in advance) can abrogate some of
      the sugar-induced negative effects, which is an example of mild stress-induced
      hormesis. This experimental model can be useful to study the effects of potential
      antiaging interventions.

PMID- 17460219
TI  - Evidence for a trade-off between survival and fitness caused by resveratrol
      treatment of Caenorhabditis elegans.
AB  - Resveratrol is a naturally occurring polyphenolic compound commonly found in
      plant-derived products, including red wine. A large number of beneficial effects
      including anticarcinogenic action and protection from atherosclerotic disease
      have been attributed to resveratrol. Increased resveratrol intake has been
      suggested as an explanation for the beneficial effects of moderate red wine
      consumption. Resveratrol also consistently extends the mean and maximum life span
      in model organisms including nematode worms. It has been suggested that
      resveratrol exerts its life-span-extending effect through calorie restriction or
      hormesis mimetic effects. We have characterized the effect of resveratrol on
      stress resistance, developmental rate, growth, and fecundity in the nematode worm
      Caenorhabditis elegans in order to determine whether the beneficial effects of
      resveratrol on life span are associated with trade-offs in terms of early life
      fitness in nematodes. We find that resveratrol treatment increases stress
      resistance, specifically to oxidative stress, and causes a small but significant
      decrease in fecundity early in life without affecting overall fecundity.
      Resveratrol increased mean and maximum life span by delaying the onset of the
      exponential increase in mortality characterizing the "dying phase" in C. elegans,
      but did not affect the dying phase itself, suggesting that it did not act by
      directly affecting metabolism.

PMID- 17460220
TI  - Influence of aging and enriched environment on motor activity and emotional
      responses in mice.
AB  - We have evaluated different behavioral parameters in ICR (CD1) female mice of
      three different ages (38-39 weeks: mature; 62 weeks: late mature; 90 weeks: old),
      and addressed the effects of an enriched housing condition. We employed the
      following battery of tests: Holeboard, open field, elevated plus-maze (EPM), and
      forced swimming test (FST). The results suggest that aging process differentially
      affects diverse aspects of behavior. With respect to motor activity, late mature
      animals were more affected by enrichment, whereas old animals appeared to be more
      affected when emotional responses were considered. We propose that the diminished
      percentage of time in the open arms of the EPM showed by enriched mice may be
      indicative of decreased novelty seeking, whereas their decreased climbing
      behavior may indicate a reduced escape-related behavior in an inescapable
      situation.

PMID- 17460221
TI  - Effects of taurine in cellular responses to oxidative stress in young and middle
      aged rat liver.
AB  - Aging is related with an increased cellular level of lipid peroxides and reactive
      oxygen species (ROS). The useful effects of taurine as an antioxidant in
      biological systems have been attributed to its capability to stabilize
      biomembranes, to scavenge ROS, and to decrease the peroxidation of unsaturated
      membrane lipids. The aim of the present study was to investigate the effects of
      taurine on malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase
      (GPx), thioredoxin reductase (TR), and endothelial nitric oxide synthase (eNOS)
      in young and middle-aged rat liver. There was not a significant difference in
      liver MDA levels between the control groups of young and middle-aged rats (P >
      0.05). However, liver GSH levels, and GPx and TR activities between the control
      groups of young and middle-aged rats were significantly different (P < 0.05).
      Liver MDA level was significantly lower in the taurine group of middle-aged rats
      (P < 0.05). Liver GSH levels, and GPx and TR activities were significantly
      increased in the taurine group of middle-aged rats when compared to the control
      group (P < 0.05). Liver MDA level was significantly lower in the taurine group of
      young rats than the ones in the control group (P < 0.05). Liver TR activity was
      significantly increased in the taurine group of young rats when compared to the
      control group (P < 0.05). Liver GPx activity was not statistically different
      between the taurine and the control groups in young rats (P > 0.05). Liver GSH
      levels were not different between the young taurine and the control groups (P >
      0.05). Immunohistochemical studies exhibited no change in eNOS activity after
      taurine injection in young rats. However, in middle-aged rats, taurine lowered
      the eNOS reactivity to the same level found in young rats. These results
      suggested that exogenous taurine might play a role in aging by means of its
      reducing effects on free radical levels in parallel to an increase in the
      antioxidant capacity.

PMID- 17460222
TI  - Videos in clinical medicine. Orotracheal intubation.

PMID- 17460223
TI  - Images in clinical medicine. Pulmonary and peritoneal ossification.

PMID- 17460224
TI  - Challenges in using observational studies to evaluate adverse effects of
      treatment.

PMID- 17460225
TI  - Mitochondrial dynamics in disease.

PMID- 17460226
TI  - Class of antiretroviral drugs and the risk of myocardial infarction.
AB  - BACKGROUND: We have previously demonstrated an association between combination
      antiretroviral therapy and the risk of myocardial infarction. It is not clear
      whether this association differs according to the class of antiretroviral drugs.
      We conducted a study to investigate the association of cumulative exposure to
      protease inhibitors and nonnucleoside reverse-transcriptase inhibitors with the
      risk of myocardial infarction. METHODS: We analyzed data collected through
      February 2005 from our prospective observational study of 23,437 patients
      infected with the human immunodeficiency virus. The incidence rates of myocardial
      infarction during the follow-up period were calculated, and the associations
      between myocardial infarction and exposure to protease inhibitors or
      nonnucleoside reverse-transcriptase inhibitors were determined. RESULTS: Three
      hundred forty-five patients had a myocardial infarction during 94,469 person
      years of observation. The incidence of myocardial infarction increased from 1.53
      per 1000 person-years in those not exposed to protease inhibitors to 6.01 per
      1000 person-years in those exposed to protease inhibitors for more than 6 years.
      After adjustment for exposure to the other drug class and established
      cardiovascular risk factors (excluding lipid levels), the relative rate of
      myocardial infarction per year of protease-inhibitor exposure was 1.16 (95%
      confidence interval [CI], 1.10 to 1.23), whereas the relative rate per year of
      exposure to nonnucleoside reverse-transcriptase inhibitors was 1.05 (95% CI, 0.98
      to 1.13). Adjustment for serum lipid levels further reduced the effect of
      exposure to each drug class to 1.10 (95% CI, 1.04 to 1.18) and 1.00 (95% CI, 0.93
      to 1.09), respectively. CONCLUSIONS: Increased exposure to protease inhibitors is
      associated with an increased risk of myocardial infarction, which is partly
      explained by dyslipidemia. We found no evidence of such an association for
      nonnucleoside reverse-transcriptase inhibitors; however, the number of person
      years of observation for exposure to this class of drug was less than that for
      exposure to protease inhibitors.

PMID- 17460227
TI  - A lethal defect of mitochondrial and peroxisomal fission.
AB  - We report on a newborn girl with microcephaly, abnormal brain development, optic
      atrophy and hypoplasia, persistent lactic acidemia, and a mildly elevated plasma
      concentration of very-long-chain fatty acids. We found a defect of the fission of
      both mitochondria and peroxisomes, as well as a heterozygous, dominant-negative
      mutation in the dynamin-like protein 1 gene (DLP1). The DLP1 protein has
      previously been implicated, in vitro, in the fission of both these organelles.
      Overexpression of the mutant DLP1 in control cells reproduced the fission defect.
      Our findings are representative of a class of disease characterized by defects in
      both mitochondria and peroxisomes.

PMID- 17460228
TI  - A national survey of physician-industry relationships.
AB  - BACKGROUND: Relationships between physicians and pharmaceutical, medical device,
      and other medically related industries have received considerable attention in
      recent years. We surveyed physicians to collect information about their financial
      associations with industry and the factors that predict those associations.
      METHODS: We conducted a national survey of 3167 physicians in six specialties
      (anesthesiology, cardiology, family practice, general surgery, internal medicine,
      and pediatrics) in late 2003 and early 2004. The raw response rate for this
      probability sample was 52%, and the weighted response rate was 58%. RESULTS: Most
      physicians (94%) reported some type of relationship with the pharmaceutical
      industry, and most of these relationships involved receiving food in the
      workplace (83%) or receiving drug samples (78%). More than one third of the
      respondents (35%) received reimbursement for costs associated with professional
      meetings or continuing medical education, and more than one quarter (28%)
      received payments for consulting, giving lectures, or enrolling patients in
      trials. Cardiologists were more than twice as likely as family practitioners to
      receive payments. Family practitioners met more frequently with industry
      representatives than did physicians in other specialties, and physicians in solo,
      two-person, or group practices met more frequently with industry representatives
      than did physicians practicing in hospitals and clinics. CONCLUSIONS: The results
      of this national survey indicate that relationships between physicians and
      industry are common and underscore the variation among such relationships
      according to specialty, practice type, and professional activities.

PMID- 17460229
TI  - Continuous positive airway pressure for obstructive sleep apnea.

PMID- 17460230
TI  - Images in clinical medicine. Torus palatinus.

PMID- 17460231
TI  - Case records of the Massachusetts General Hospital. Case 13-2007. A 46-year-old
      woman with gynecologic and intestinal cancers.

PMID- 17460232
TI  - Cardiovascular risks of antiretroviral therapy.

PMID- 17460233
TI  - Tolls and beyond--many roads to vaccine immunity.

PMID- 17460234
TI  - Familial hypercholesterolemia.

PMID- 17460235
TI  - Imatinib in chronic myeloid leukemia.

PMID- 17460236
TI  - Mutant neurogenin-3 in congenital malabsorptive diarrhea.

PMID- 17460237
TI  - Public reporting and pay for performance.

PMID- 17460238
TI  - Mortality after release from prison.

PMID- 17460239
TI  - Concussion.

PMID- 17460240
TI  - Proceduralists--leading patient-safety initiatives.

PMID- 17460241
TI  - Morphometry of the retrobulbar human optic nerve: comparison between conventional
      sonography and ultrafast magnetic resonance sequences.
AB  - PURPOSE: To compare different methods for quantification of optic nerve and nerve
      sheath diameter. To apply a novel magnetic resonance protocol using half-Fourier
      acquired single-shot turbo spin-echo (HASTE) sequences to analyze optic nerve
      dimensions. METHODS: Measurements were taken in right eyes of 33 subjects whose
      median age was 25 years. A-scan ultrasonography was repeated three times in
      straight gaze. B-scan ultrasonography was repeated three times in straight gaze
      and abduction. HASTE sequences were applied in straight gaze, analyzed twice by
      two different radiologists, and completely repeated in a subset of 10 subjects;
      95% confidence intervals and coefficients of variation were calculated. RESULTS:
      HASTE sequences yielded high contrast between cerebrospinal fluid and optic nerve
      parenchyma. Acquisition time for each sequence was 1.5 seconds per slice. Optic
      nerve diameters decreased from 3.23 mm at 5 mm to 2.67 mm at 15 mm behind the
      eye. Sheath diameters decreased from 5.72 mm to 3.98 mm. A- and B-scan
      ultrasonography yielded significantly smaller diameters. For HASTE sequences, the
      coefficients of variation ranged from 2% to 7% and were significantly smaller
      than those obtained with ultrasonographic measurements (9%-13%). CONCLUSIONS: The
      precision of magnetic resonance imaging exceeds that of ultrasonographic methods
      for determining optic nerve and nerve sheath diameters. HASTE sequences appear
      particularly appropriate for investigating the retrobulbar optic nerve complex
      and may be useful in future studies quantifying axonal loss within the optic
      nerve.

PMID- 17460242
TI  - The spatial distribution of monosomy 3 and network vasculogenic mimicry patterns
      in uveal melanoma.
AB  - PURPOSE: Monosomy of chromosome 3 and network vasculogenic mimicry patterns are
      associated with death in patients with uveal melanoma (UM). Networks are
      typically found in confined areas within the tumor, whereas the intratumor
      distribution of chromosome 3 aberrations is unknown. This study was conducted to
      assess the spatial correlation among chromosome 3 aberrations and networks in UM.
      METHODS: Vasculogenic mimicry patterns, proliferative activity, and cell type
      were characterized in 15 enucleated eyes with primary UM. Cells were isolated by
      laser capture microdissection (LCM) from two tumor regions and one normal retina
      area from each tissue block. In the eight tumors containing networks, the cells
      were microdissected from one area with networks and a different area without
      networks. In seven tumors without networks, cells were microdissected from two
      distinct tumor areas. The presence of chromosome 3 aberrations was assessed by
      microsatellite analysis (MSA) in each LCM sample. RESULTS: Useful MSA data was
      obtained from 43 of the 45 samples. Monosomy 3 was detected in 16 samples of
      eight tumors. There was no intratumor heterogeneity for monosomy 3, regardless of
      the existence of heterogeneity in networks, cell type, or proliferative activity
      across the two samples from the same tumor. Networks were associated with the
      presence of monosomy 3 throughout the entire tumor (P = 0.02). CONCLUSIONS: Of
      the histologic prognostic factors of metastasis in UM studied, only the presence
      of a network vasculogenic mimicry pattern but not its location is associated with
      monosomy 3. This suggests that monosomy 3 may contribute to but is not sufficient
      for the development of the network pattern.

PMID- 17460243
TI  - Histogenesis of the intravitreal membrane and secondary vitreous in the mouse.
AB  - PURPOSE: The intravitreal membrane (IVM) is a membranous structure between the
      primary and secondary vitreous bodies in developing mammalian eyes. In this
      study, for the first time the histogenesis of the IVM and the relationship
      between the hyaloid vasculature and the IVM was characterized in newborn mice.
      METHODS: Eyes of mice less than 12 days old were fixed and embedded. From these,
      serial paraffin-embedded sections were made for lectin histochemistry,
      immunohistochemistry, and picrosirius red (PSR) staining, and ultrathin sections
      were made for transmission electron microscopy (TEM). Eight biotinylated lectins
      and antibodies for laminin and type IV collagen were used. RESULTS: Among the
      eight lectins tested, concanavalin A (Con A) agglutinin, Ricinus communis
      agglutinin I, and wheat germ agglutinin demonstrated strong positive staining in
      the IVM and vitreous fibrils of the primary and secondary vitreous bodies. They
      also bound to the internal limiting membrane (ILM) of the retina. At
      postgestational day 4, the secondary vitreous first appeared between the ILM and
      the vasa hyaloidea propria (VHP). Immunohistochemical staining revealed that the
      IVM consists of extracellular matrix components including laminin and type IV
      collagen, whereas PSR staining and TEM showed that collagen fibrils in the IVM
      are bundled and continuous with the basement membrane of hyaloid capillaries or
      the VHP. CONCLUSIONS: Lectin histochemistry and immunohistochemistry provided
      good methods for visualizing the structures of the IVM and vitreous fibrils.
      These results suggest that the IVM is separated from the basement membrane of the
      retinal ILM along with the vascular network of the VHP when the secondary
      vitreous begins to form.

PMID- 17460244
TI  - Platelet-activating factor overturns the transcriptional repressor disposition of
      Sp1 in the expression of MMP-9 in human corneal epithelial cells.
AB  - PURPOSE: Matrix metalloproteinase (MMP)-9 is induced in corneal epithelial cells
      stimulated with platelet-activating factor (PAF), and interferes with the normal
      reepithelialization of wounded cornea. Here the transcriptional regulation of MMP
      9 gene expression by PAF was investigated in human corneal epithelial cells
      (HCECs). METHODS: DNA-binding activity of NFkappaB, Sp1, and AP-1 was determined
      in quiescent and PAF-stimulated HCECs by electrophoretic mobility shift assay
      (EMSA). A series of 5' deleted human MMP-9 promoter-luciferase reporter
      constructs was transiently transfected into HCECs, and luciferase activity was
      examined after stimulation with PAF. Mutagenesis and specific deletions of some
      elements in the MMP-9 promoter were also introduced and analyzed. Phosphorylation
      of Sp1 and MEK/ERK pathway proteins was examined by Western blot analysis.
      Activation of Sp1 and MMP-9 was also determined by ELISA and zymography,
      respectively, in the absence or presence of the MEK inhibitor PD98059. RESULTS:
      DNA-binding activity of NFkappaB, Sp1, and AP-1 was upregulated by PAF with a
      peak at 1 hour after stimulation. A region spanning -670 to -460 relative to the
      transcription start point was required for the induction of the MMP-9 promoter by
      PAF. Mutation of the -79AP-1 or -600NFkappaB motif reduced the activity of MMP-9
      promoter and the induction of gene expression by PAF. In untreated HCECs,
      mutation of the -558Sp1 motif upregulated gene expression, but it caused a
      significant decrease in the promoter activity induced by PAF. Inhibition of MEK
      activity eliminated the PAF-induced phosphorylation and activation of Sp1 and
      abolished the upregulation of MMP-9 expression and activity. CONCLUSIONS: These
      findings demonstrate that collaboration between several regulatory elements is
      required for the induction of MMP-9 promoter activity by PAF and that PAF
      overturns the repressor effect of Sp1 through activation of the MEK/ERK signaling
      cascade.

PMID- 17460245
TI  - Increased sensitivity to light-induced damage in a mouse model of autosomal
      dominant retinal disease.
AB  - PURPOSE: To describe a sensitivity to light-induced damage associated with
      expression of a T17M mutant human rhodopsin (hT17M) transgene in mice, with the
      goal of minimizing retinal injury during the subretinal delivery of rAAV-mediated
      gene therapy. METHODS: Mice were bred to express the hT17M rhodopsin transgene in
      a line that was hemizygous null for wild-type mouse rhodopsin (mrho(+/-)), and
      the eyes of transgenic mice and nontransgenic littermates were exposed for 2.5
      minutes to unilateral illumination with fiber-optic light ranging from 5,000 to
      10,000 lux. Funduscopic images were made with a handheld camera (Genesis; Kowa
      Company, Ltd., Tokyo, Japan). Full-field scotopic electroretinographic analysis
      (ERG) was performed to measure loss of retinal function. Morphometry in the light
      microscope was used to measure loss of rod photoreceptors. TUNEL staining and a
      nucleosome release assay were used to measure levels of apoptosis in retinal
      specimens. RESULTS: mrho(+/-);hT17M mice exhibited a sensitivity to light-induced
      damage that caused severe loss of a- and b-wave ERG responses. hT17M transgenic
      mice on the mrho(+/+) background were equally sensitive to light-induced damage.
      Histologic analysis showed a concomitant loss of photoreceptors and TUNEL
      labeling of fragmented DNA in rod photoreceptor cells, demonstrating that the
      damage occurred via an apoptotic pathway. Nontransgenic littermate mice were not
      affected by this exposure to light. Mice expressing an hP23H mutant human
      rhodopsin transgene were minimally sensitive to light-induced damage at these
      intensities, in comparison to hT17M mice. Treating the hT17M mice with an
      equivalent regimen of exposure to red light was less damaging to the retina, as
      measured by ERG and histology. CONCLUSIONS: Expression of a human hT17M mutant
      rhodopsin transgene in mice is associated with photoreceptor apoptosis in
      response to moderate exposure to light. This phenotype was not observed in
      nontransgenic littermates or in mice expressing an hP23H mutant human rhodopsin
      transgene. The results suggest that elimination of the glycosylation site at N15
      is associated with increased sensitivity to light-induced damage.

PMID- 17460246
TI  - Upregulation of TGF-beta-induced tissue transglutaminase expression by PI3K-Akt
      pathway activation in human subconjunctival fibroblasts.
AB  - PURPOSE: Excessive scarring in subconjunctival tissues after filtering surgery
      seems to be characterized by aberrant extracellular matrix (ECM) production, and
      tissue transglutaminase (tTgase) plays an important role in this process. In the
      present study, the effects of transforming growth factor (TGF)-beta2 on the
      expression of tTgase, its activity in subconjunctival fibroblasts and whether the
      effects of TGF-beta are mediated by prosurvival signaling pathways were examined.
      METHODS: Primary subconjunctival fibroblasts treated with TGF-beta2 were examined
      for the expression of tTgase with Western blot analysis. The modulation of
      extracellular tTgase activity by TGF-beta2 was measured by both the formation of
      fibronectin polymers and the ECM protein incorporation of fluorescein cadaverine.
      The expression of tTgase was analyzed by immunofluorescence staining and Western
      blot analysis of subconjunctival fibroblasts that were transiently transfected
      with an Akt dominant negative mutant gene or were treated with an Akt inhibitor
      or tTgase siRNA. RESULTS: Treatment of subconjunctival fibroblasts with TGF-beta2
      caused an increase in activation and expression of tTgase. The effects of TGF
      beta stimulation of subconjunctival fibroblasts were twofold, causing both rapid
      activation of the ERK pathway within minutes of treatment and a more delayed
      activation of the phosphatidylinositol3-kinase-protein kinase B (PKB)/Akt
      pathway; however, only Akt activation was necessary for TGF-beta-induced tTgase
      expression. Transient transfection of subconjunctival fibroblasts with an Akt
      dominant negative mutant gene, or treatment with an Akt inhibitor (but not with
      an ERK inhibitor) or tTgase siRNA led to decreased activation and expression of
      tTgase. CONCLUSIONS: TGF-beta2 activated the PI3K-Akt pathway, and this
      activation was essential for the expression and activity of tTgase in
      subconjunctival fibroblasts. The results indicate a novel biological function of
      the PI3K-Akt pathway in subconjunctival fibroblasts. Elevated expression and
      activity of tTgase may play an important role in the pathogenesis of diseases
      related to wound healing and fibrogenic reactions in subconjunctival fibroblasts.

PMID- 17460247
TI  - Bestrophin gene mutations cause canine multifocal retinopathy: a novel animal
      model for best disease.
AB  - PURPOSE: Canine multifocal retinopathy (cmr) is an autosomal recessive disorder
      of multiple dog breeds. The disease shares a number of clinical and pathologic
      similarities with Best macular dystrophy (BMD), and cmr is proposed as a new
      large animal model for Best disease. METHODS: cmr was characterized by
      ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1
      (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in
      the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid
      5'- and 3'-RACE. Expression of the canine gene transcripts and protein was
      analyzed by Northern and Western blotting and immunocytochemistry. All exons and
      the flanking splice junctions were screened by direct sequencing. RESULTS: The
      clinical phenotype and pathology of cmr closely resemble lesions of BMD. Canine
      VMD2 spans 13.7 kb of genomic DNA on CFA18 and shows a high level of conservation
      among eukaryotes. The transcript is predominantly expressed in RPE/choroid and
      encodes bestrophin, a 580-amino acid protein of 66 kDa. Immunocytochemistry of
      normal canine retina demonstrated specific localization of protein to the RPE
      basolateral plasma membranes. Two disease-specific sequence alterations were
      identified in the canine VMD2 gene: a C(73)T stop mutation in cmr1 and a G(482)A
      missense mutation in cmr2. CONCLUSIONS: The authors propose these two spontaneous
      mutations in the canine VMD2 gene, which cause cmr, as the first naturally
      occurring animal model of BMD. Further development of the cmr models will permit
      elucidation of the complex molecular mechanism of these retinopathies and the
      development of potential therapies.

PMID- 17460249
TI  - Rasch analysis of the daily living tasks dependent on vision (DLTV).
AB  - PURPOSE: To examine internal consistency, refine the response scale, and obtain a
      linear scoring system for the visual function instrument, the Daily Living Tasks
      Dependent on Vision (DLTV). METHODS: Data were available from 186 participants
      with a clinical diagnosis of AMD who completed the 22-item DLTV (DLTV-22)
      according to four-point ordinal response scale. An independent group of 386
      participants with AMD were administered a reduced version of the DLTV with 11
      items (DLTV-11), according to a five-point response scale. Rasch analysis was
      performed on both datasets and used to generate item statistics for measure
      order, response odds ratios per item and per person, and infit and outfit mean
      square statistics. The Rasch output from the DLTV-22 was examined to identify
      redundant items and for factorial validity and person item measure separation
      reliabilities. RESULTS: The average rating for the DLTV-22 changed monotonically
      with the magnitude of the latent person trait. The expected versus observed
      average measures were extremely close, with step calibrations evenly separated
      for the four-point ordinal scale. In the case of the DLTV-11, step calibrations
      were not as evenly separated, suggesting that the five-point scale should be
      reduced to either a four- or three-point scale. Five items in the DLTV-22 were
      removed, and all 17 remaining items had good infit and outfit mean squares. PCA
      with residuals from Rasch analysis identified two domains containing 7 and 10
      items each. The domains had high person separation reliabilities (0.86 and 0.77
      for domains 1 and 2, respectively) and item measure reliabilities (0.99 and 0.98
      for domains 1 and 2, respectively). CONCLUSIONS: With the improved internal
      consistency, establishment of the accuracy and precision of the rating scale for
      the DLTV and the establishment of a valid domain structure we believe that it
      constitutes a useful instrument for assessing visual function in older adults
      with age-related macular degeneration.

PMID- 17460248
TI  - Functional comparisons of visual arrestins in rod photoreceptors of transgenic
      mice.
AB  - PURPOSE: To examine the biochemical characteristics of rod and cone arrestin with
      respect to their ability to quench the activity of light-activated rhodopsin in
      transgenic mice. METHODS: The mouse rod opsin promoter was used to drive
      expression of mouse cone arrestin in rod photoreceptor cells of rod arrestin
      knockout (arr1-/-) mice. Suction electrode recordings from single rods were
      performed to investigate cone arrestin's ability to quench the catalytic activity
      of light-activated rhodopsin. In addition, the ability of cone arrestin to
      prevent light-induced retinal damage caused by prolonged activation of the
      phototransduction cascade was assessed. RESULTS: Two independent lines of
      transgenic mice were obtained that expressed cone arrestin in rod photoreceptors,
      and each was bred into the arr1-/- background. Flash responses measured by
      suction electrode recordings showed that cone arrestin reduced signaling from
      photolyzed rhodopsin but was unable to quench its activity completely. Consistent
      with this observation, expression of mouse cone arrestin conferred dose-dependent
      protection against photoreceptor cell death caused by low light exposure to arr1
      /- retinas, but did not appear to be as effective as rod arrestin. CONCLUSIONS:
      Cone arrestin can partially substitute for rod arrestin in arr1-/- rods, offering
      a degree of protection from light-induced damage and increasing the extent of
      rhodopsin deactivation in response to flashes of light. Although earlier work has
      shown that rod arrestin can bind and deactivate cone pigments efficiently, the
      results suggest that cone arrestin binds light-activated, phosphorylated
      rhodopsin less efficiently than does rod arrestin in vivo. These results suggest
      that the structural requirements for high-affinity binding are fundamentally
      distinct for rod and cone arrestins.

PMID- 17460250
TI  - Circulating inflammatory markers and hemostatic factors in age-related
      maculopathy: a population-based case-control study.
AB  - PURPOSE: To examine the relationship between circulating inflammatory markers,
      hemostatic factors, and age-related maculopathy (ARM). METHODS: A population
      based, cross-sectional case-control study drawn from the Blue Mountains Eye Study
      included 159 early and 38 late ARM cases, and 433 controls matched for age,
      gender, and smoking. ARM lesions were assessed from retinal photographs according
      to the Wisconsin ARM grading system. Circulating inflammatory markers (high
      sensitivity C-reactive protein [hsCRP], intercellular adhesion molecule [ICAM]-1,
      and interleukin [IL]-6), white cell count (WCC), and hemostatic factors
      (fibrinogen, homocysteine, plasminogen activator inhibitor [PAI]-1 and von
      Willebrand factor [vWF]) were assessed. Age, gender, current smoking, body mass
      index, hypertension, history of stroke, and cardiovascular events were adjusted
      for. Adjusted mean levels of each marker were compared between persons with early
      ARM, those with late ARM, and control subjects, and are presented as
      probabilities. Adjusted associations with ARM were examined continuously (per
      SD), and are presented as odds ratios (ORs) and 95% confidence intervals (CIs).
      Summarizing z scores for inflammation and hemostatic dysfunction were calculated.
      RESULTS: Increased PAI-1 level was associated with both early (OR 1.2, 95% CI 1.0
      1.4 per SD increase) and late ARM (OR 1.3, 95% CI 0.9-1.9 per SD increase).
      Elevated ICAM-1 level was marginally associated with late ARM (OR 1.3, 95% CI 1.0
      1.7 per SD increase). No other significant associations were found between the
      remaining inflammatory or hemostatic markers and either early or late ARM.
      Summarized z scores for inflammatory or hemostatic markers also did not suggest
      any associations. CONCLUSIONS: There was no consistent pattern of association
      found between ARM and circulating inflammatory markers or hemostatic factors in
      this population-based case-control study.

PMID- 17460251
TI  - Knowledge, attitudes, and beliefs about dilated eye examinations among African
      Americans.
AB  - PURPOSE: To understand factors that influence African-Americans' attitude toward
      eye examinations. METHODS: Ten focus groups were conducted with 86 African
      Americans. Four focus groups were conducted with people 65 years of age and older
      who had not received a dilated fundus examination (DFE) in the past 2 years, two
      groups were held with people 65 years of age and older who had had a recent DFE,
      and two groups each were held with people 40 to 64 years of age, with and without
      recent DFEs. Focus group interviews were conducted by using a moderator guide to
      address perceived benefits of and barriers to getting an eye examination;
      motivators for getting DFEs; and knowledge of eye examinations, glaucoma, and
      diabetic retinopathy. Participants also completed a questionnaire that provided
      demographic information. Quantitative and qualitative analyses were conducted.
      RESULTS: Cost or lack of sufficient insurance was identified as the most
      important barrier to getting a DFE. Also frequently mentioned was not having any
      symptoms and being too busy. The most frequently cited benefit of getting a DFE
      was to help prevent eye disease, whereas the most frequently reported motivating
      factor was experiencing a vision problem. Regarding knowledge, many people did
      not know the risk factors for glaucoma, but seemed to have a better understanding
      of how to reduce the effects of diabetes on their eyes. CONCLUSIONS: Study
      findings identified important links between financial resources and experiencing
      a vision problem and the adoption of preventive eye care in an urban African
      American population.

PMID- 17460252
TI  - The association between retinal vascular network geometry and cognitive ability
      in an elderly population.
AB  - PURPOSE: To test the hypothesis that parameters of retinal vascular network
      geometry are significantly associated with cognition. METHODS: Three hundred
      twenty-one community-dwelling, surviving participants in the Scottish Mental
      Survey of 1932 from the Lothian region of Scotland (Lothian Birth Cohort 1921;
      all born in 1921 and aged approximately 83 when tested) underwent fundus
      photography and the following psychometric tests: Wechsler Logical Memory, Verbal
      Fluency, and Raven's Standard Progressive Matrices. In addition, a general
      cognitive ability score (g) was obtained from these three correlated tests of
      cognition. The following parameters of the retinal vascular network geometry were
      measured: central retinal arterial and venular equivalents (CRAE and CRVE,
      respectively), arteriovenous ratio (AVR), suboptimality of the median branching
      coefficient (BC), and median angle of the five most proximal arteriolar
      bifurcations. General linear modeling (GLM; analysis of covariance [ANCOVA]) was
      used to measure associations, with gender, APOE e4 status, presence of diabetes,
      smoking status (current, ex-, or never), and history of cerebrovascular disease
      as fixed factors and the following covariables: IQ at age 11, logMAR (logarithm
      of the minimum angle of resolution) near visual acuity of the better-seeing eye,
      years of full-time formal education, occupational social class category, systolic
      and diastolic blood pressure, and alcohol units per week. RESULTS: Deviation of
      the median BC from optimality was significantly associated with general cognitive
      ability (g) (eta(2) = 0.034, P = 0.02) and verbal fluency (eta(2) = 0.037, P =
      0.01), whereas deviation of the angle at arteriolar bifurcations from optimality
      was significantly associated with logical memory (eta(2) = 0.026, P = 0.03).
      CRAE, CRVE, and AVR did not contribute significantly to any cognitive test
      scores. Conclusions The association of suboptimal retinal vascular network
      geometry and cognition was shown in this study. It supports the concept that the
      retinal microvasculature acts as a surrogate marker for the cerebral
      microvasculature.

PMID- 17460253
TI  - Benzalkonium chloride induces dephosphorylation of Myosin light chain in cultured
      corneal epithelial cells.
AB  - PURPOSE: Phosphorylation of myosin light chain (MLC) is essential for the
      contractility of the actin cytoskeleton, which regulates barrier integrity,
      adhesion, and migration. This study was conducted to investigate the effect of
      benzalkonium chloride (BAK), a preservative in topical ophthalmic formulations,
      on MLC phosphorylation in primary cultures of bovine corneal epithelial cells
      (BCECs). METHODS: MLC phosphorylation was assessed by urea-glycerol gel
      electrophoresis followed by Western blot analysis. Activation of RhoA, which
      inhibits MLC phosphatase through Rho kinase, was examined by immunoprecipitation.
      The release of adenosine triphosphate (ATP) was measured by the luciferase
      luciferin bioluminescence technique. RESULTS: Positive expression of MLC kinase
      (MLCK) was found at the mRNA and protein levels by RT-PCR and Western blot
      analysis, respectively. Exposure to BAK for 10 to 20 minutes at concentrations of
      0.0005%, 0.001%, and 0.003% reduced MLC phosphorylation by more than 30%. In
      addition, BAK led to thinning of the cortical actin and a decrease in cell
      adhesion. However, RhoA activity was found to increase with BAK treatment.
      Similar to BAK, ATP-depletion (induced by both antimycin-A and hypoxia) led to
      MLC dephosphorylation. BAK exposure also showed acute ATP release. CONCLUSIONS:
      BAK induces acute ATP release and concomitant MLC dephosphorylation in bovine
      corneal epithelial cells. The dephosphorylation, presumably due to ATP loss, is
      indicative of a loss of contractility of the actin cytoskeleton that could affect
      cellular functions contributing to the maintenance of epithelial barrier
      integrity.

PMID- 17460254
TI  - Mitomycin C upregulates IL-8 and MCP-1 chemokine expression via mitogen-activated
      protein kinases in corneal fibroblasts.
AB  - PURPOSE: To investigate the expression of chemokines and their signaling pathways
      after application of mitomycin C (MMC) to corneal fibroblasts. METHODS: Primary
      porcine and human corneal fibroblasts from passages 3 to 6 were treated with MMC
      at concentrations of 0.05, 0.1, or 0.2 mg/mL for 1, 2, 5, or 10 minutes. The
      relative expression of interleukin-8 (IL-8) and monocyte chemoattractant protein
      1 (MCP-1) were investigated with reverse transcription, and quantitative real
      time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay
      (ELISA). The effects of MMC on the activation of kinases were analyzed by Western
      blot analysis with specific antiphosphokinase antibodies. The signaling pathways
      by which MMC regulates the expression of IL-8 and MCP-1 were evaluated by
      pharmacological kinase-specific inhibitors. RESULTS: The expression of IL-8 and
      MCP-1 were upregulated after MMC treatment in a time- and concentration-dependent
      manner. Furthermore, the upregulated expression of IL-8 and MCP-1 increased with
      longer incubation time. MMC treatment enhanced the phosphorylation of p38, JNK,
      and ERK at different time points. The MMC-related IL-8 and MCP-1 expression was
      inhibited by both a p38 inhibitor (SB203580) and an ERK inhibitor (PD98059). A
      JNK inhibitor (SP600125) reduced the expression of MMC-induced MCP-1 but not of
      IL-8. CONCLUSIONS: MMC treatment upregulated the expression of IL-8 and MCP-1
      mRNA and protein secretion by the activation of mitogen-activated protein kinases
      (MAPKs) in corneal fibroblasts.

PMID- 17460255
TI  - The cornea in Sjogren's syndrome: an in vivo confocal study.
AB  - PURPOSE: To analyze the in vivo morphology of corneal cells and nerves in dry eye
      associated with primary (SSI) and secondary (SSII) Sjogren's syndrome and to
      study its relationship with the clinical evaluation. METHODS: Thirty-five
      patients with SS and 20 age- and gender-matched control subjects were studied.
      Confocal microscopy was used to investigate corneal thickness, epithelial and
      stromal cellular density, and subbasal plexus morphology. RESULTS: Corneal
      central thickness was 514.74 +/- 19.85 microm in the SS group and 550 +/- 21.46
      microm in the control group (P < 0.0001, t-test); stromal central thickness was
      456.62 +/- 18.05 microm in the SS group and 487.35 +/- 20.40 microm in the
      control group (P < 0.0001). The density of the superficial epithelial cells in
      the SSI and SSII groups was 965.40 +/- 96.00 and 999.80 +/- 115.67 cells/mm(2),
      respectively, and 1488.55 +/- 133.74 cells/mm(2) in the control group (P < 0.001,
      ANOVA). The number of subbasal nerves was 3.34 +/- 0.76 in the SS group and 5.10
      +/- 0.79 in the control group (P < 0.0001, t-test). The average grade of nerve
      tortuosity was 2.62 +/- 0.94 in the SS group and 1.20 +/- 0.70 in the control
      group (P < 0.0001). Statistically significant correlations were found between
      clinical data and confocal microscopy data. CONCLUSIONS: Corneal thickness,
      cells, and nerves show morphologic changes in patients with dry eye associated
      with SS. The in vivo confocal study of these alterations may be important in
      better understanding the complexity of the ocular surface morphofunctional unit
      and the potentials of therapeutic approaches for the control of the phlogistic
      process and neuroprotection.

PMID- 17460256
TI  - A pharmacokinetic and safety evaluation of an episcleral cyclosporine implant for
      potential use in high-risk keratoplasty rejection.
AB  - PURPOSE: To determine the short and long-term pharmacokinetics and assess the
      toxicity of a cyclosporine (CsA) episcleral implant for the prevention of high
      risk keratoplasty rejection. METHODS: CsA episcleral implants were made with a
      high (implant A) or low (implant B) release rate, and in vitro release rates were
      performed. Short-term pharmacokinetics were performed in rabbits using implant B,
      and the spatial and temporal spread of drug was observed by sampling from
      multiple corneal and conjunctival sites at 3 and 72 hours. Implant A was used in
      long-term pharmacokinetic studies in dogs aged more than 1 year. An ocular
      toxicity study was performed in dogs older than 1 year. RESULTS: A high release
      rate was observed with both implants over the initial 5 months followed by a
      steady state release. The cumulative release over the 400-day assay period from
      implants A and B was 3.8 +/- 0.3 and 2.3 +/- 0.3 mg, respectively. In the short
      term pharmacokinetic studies, the cornea had CsA concentrations of 0.15 +/- 0.06,
      0.07 +/- 0.02, and 0.05 +/- 0.02 microg/mg at sites centered 8, 13, and 18 mm
      away from the implant site, respectively. In the long-term pharmacokinetic
      studies, corneal CsA levels ranged from 0.18 +/- 0.06 to 0.009 +/- 0.004
      microg/mg during the 1-year study. There were no signs of ocular toxicity at 1
      year. CONCLUSIONS: Episcleral implants are safe and effective at delivering
      therapeutic CsA levels to the cornea to potentially prevent corneal allograft
      rejection. The implant can be surgically inserted at the time of penetrating
      keratoplasties, since the implant achieves therapeutic levels as early as 3
      hours.

PMID- 17460257
TI  - Nanoparticles sustain expression of Flt intraceptors in the cornea and inhibit
      injury-induced corneal angiogenesis.
AB  - PURPOSE: To determine whether long-term expression of intraceptors can be
      achieved using plasmid albumin nanoparticles and whether nanoparticles can
      inhibit and cause regression of murine corneal neovascularization induced by
      mechanical-chemical trauma. METHODS: Albumin nanoparticles encapsulating
      pCMV.Flt23K were developed as a lyophilized product that is easily redispersed in
      an aqueous medium. Nanoparticles were injected into the corneas of uninjured
      BALB/c mice and observed for toxicity for 3 weeks. Entry of nanoparticles into
      corneal cells was demonstrated through transmission electron microscopy and
      confocal imaging. Naked pCMV.Flt23K, nanoparticles encapsulating pCMV.Flt23K, or
      empty pCMV nanoparticles were injected into uninjured mouse corneas. These
      corneas were subjected to mechanical alkali trauma 3 weeks after injection.
      RESULTS: Nanoparticles were nontoxic to the cornea and entered into corneal
      keratocyte cytoplasm. They persisted for at least 4 weeks in the cornea,
      expressed effective intraceptor levels for at least 5 weeks, and reduced corneal
      neovascularization by approximately 40% (P = 0.035) at 5 weeks after
      administration. CONCLUSIONS: Albumin nanoparticles are not toxic to the cornea
      and can express intraceptors for extended periods that are effective in
      suppressing injury-induced corneal neovascularization.

PMID- 17460258
TI  - Photo cross-linkable Biodendrimers as ophthalmic adhesives for central
      lacerations and penetrating keratoplasties.
AB  - PURPOSE: Biodendrimer-based hydrogel adhesives were derived from biocompatible
      building blocks and poly(ethylene glycol) of 3,400, 10,000 and 20,000 g/mole. The
      leaking pressures were determined for these adhesives when used to seal 4.1-mm
      central lacerations and penetrating keratoplasties (PKPs) in enucleated porcine
      eyes. METHODS: Three biodendrimers, ([G1]-PGLSA-MA)(2)-PEG(3,400), ([G1]-PGLSA
      MA)(2)-PEG(10,000), and ([G1]-PGLSA-MA)(2)-PEG(20,000), at a range of weight
      percents were each photo cross-linked in the presence of a photo-initiator to
      form a hydrated network. These biodendrimer-based adhesives were applied directly
      to a 4.1-mm linear central laceration. In a PKP, the corneal button was initially
      secured with 8 or 16 sutures and then sealed with the adhesive. RESULTS: For the
      4.1-mm central lacerations, the ([G1]-PGLSA-MA)(2)-PEG(3,400) at 20% and 40%
      wt/vol, the ([G1]-PGLSA-MA)(2)-PEG(10,000) at 10 and 20% wt/vol, and the ([G1]
      PGLSA-MA)(2)-PEG(20,000) at 20% wt/vol held to leaking pressures above 200 mm Hg.
      In the autograft with 16 sutures, the 20% wt/vol of the ([G1]-PGLSA-MA)(2)
      PEG(3,400), ([G1]-PGLSA-MA)(2)-PEG(10,000), and ([G1]-PGLSA-MA)(2)-PEG(20,000)
      held to a pressure at or above 100 mm Hg. In the autograft with eight sutures,
      the ([G1]-PGLSA-MA)(2)-PEG(10,000) and ([G1]-PGLSA-MA)(2)-PEG(20,000)
      formulations at 20% wt/vol held to leaking pressures of 85 +/- 22 and 80 +/- 30
      mm Hg, respectively. CONCLUSIONS: The 10% wt/vol ([G1]-PGLSA-MA)(2)-PEG(10,000)
      formulation withheld leaking pressures above 200 mm Hg when used to secure a 4.1
      mm central laceration. The 20% wt/vol ([G1]-PGLSA-MA)(2)-PEG(10,000) and ([G1]
      PGLSA-MA)(2)-PEG(20,000) formulations, with 8 or 16 sutures, secured the PKP well
      above normal IOP. Biodendrimer-based adhesives are of potential use for repairing
      corneal wounds.

PMID- 17460259
TI  - Localization of ZO-1 in the nucleolus of corneal fibroblasts.
AB  - PURPOSE: Within the multidomain structure of ZO-1 are motifs responsible for ZO
      1's localization to intercellular junctions and its newly demonstrated
      localization to the leading edge of lamellipodia in corneal fibroblasts. Since ZO
      1 also has two nuclear localization signals, this study was undertaken to
      determine whether stimuli associated with wounding would induce nuclear
      translocation of ZO-1 METHODS: Immunocytochemistry and immunoblot analysis were
      used to localize endogenous and exogenous ZO-1 in nuclear and cytoplasmic sites
      in corneal fibroblasts and 293T fibroblasts, with and without myc-ZO-1
      transfection. Cells were serum starved by growth for 48 hours in DMEM/F12 with
      0.2% FBS and subsequently were either scrape wounded or treated with 10% FBS,
      PDGF, or FGF-2 for 6 hours. For immunoblot analysis, after lysis, the nuclear and
      cytosolic fractions were separated and analyzed by SDS-PAGE. Cells on companion
      coverslips were fixed with 3% p-formaldehyde and permeabilized with 1% Triton
      before immunocytochemical detection of ZO-1 and nuclear proteins. RESULTS: ZO-1
      was rarely detected in the nucleus of serum-starved corneal fibroblasts. In
      contrast, it colocalized with nucleolin in the nucleoli of corneal fibroblasts
      after serum-starved cells were treated with 10% FBS, PDGF, or FGF-2. Immunoblot
      analysis confirmed the immunocytochemical results: Little ZO-1 was detected in
      the nuclear fraction of lysates of serum-starved cells, but ZO-1 was found in the
      nuclear fractions of rabbit corneal and 293T fibroblasts treated with 10% FBS,
      PDGF, or FGF-2. Furthermore in scrape-wounded corneal fibroblasts, ZO-1 was
      localized to nucleoli of both serum-starved and serum-treated cells. CONCLUSIONS:
      Localization of ZO-1 to nucleoli of corneal and 293T fibroblasts under
      proliferative and promigratory conditions suggests a physiologically significant
      interaction of ZO-1 with proteins in nucleoli during the healing process.

PMID- 17460261
TI  - Reproducibility of endothelial assessment during corneal organ culture:
      comparison of a computer-assisted analyzer with manual methods.
AB  - PURPOSE: To investigate the reproducibility of endothelial assessment of organ
      cultured corneas with the computer-assisted Sambacornea analyzer in comparison
      with manual METHODS: methods. Seven observers of two eye banks determined the
      endothelial cell density (ECD) of 30 corneas through a grid overlay placed on
      endothelial photographs using two manual modes, unaided (naked-eye) and pointing
      (point-out). ECD was measured with the analyzer, first in automated mode, where
      analysis was completely machine determined, and then in touched-up mode, where
      the observer selected the analysis zone and corrected poorly drawn cell borders.
      Interobserver variability of ECD for the different methods was compared.
      Reproducibility of morphometry parameters was determined for the touched-up mode.
      RESULTS: Interobserver variability was +/-19.2% (95% confidence interval [CI],
      13.0-25.4) and +/-17.6% (95% CI, 11.9-23.3) for the naked-eye and point-out mode,
      respectively, whereas the touched-up mode gave the least variability of +/-9.6%
      (95% CI, 6.5-12.7), confirmed by the highest intraclass correlation coefficient
      of 0.95 (95% CI, 0.91-0.97). Interobserver variability increased with worsening
      image quality. Manual modes underestimated ECD (naked-eye by a mean 10.7% [SD,
      2.9%]; point-out by a mean 6.9% [SD, 2.3%]), whereas the automated mode
      overestimated ECD by a mean 14.7% (SD, 24.3%). Reproducibility of morphometric
      parameters by the touched-up mode was acceptable but was influenced by
      endothelial pleomorphism. CONCLUSIONS: Manual counting shows systematic
      underestimation of ECD with high interobserver variability. The analyzer in
      automated mode overestimates ECD and is absolutely unreliable. Detection of cell
      contours by the specific algorithm, combined with manual correction by a skilled
      technician, appears to be the most reliable method of ECD and morphometry
      determination.

PMID- 17460260
TI  - Comparative analysis of human conjunctival and corneal epithelial gene expression
      with oligonucleotide microarrays.
AB  - PURPOSE: To determine global mRNA expression levels in corneal and conjunctival
      epithelia and identify transcripts that exhibit preferential tissue expression.
      METHODS: cDNA samples derived from human conjunctival and corneal epithelia were
      hybridized in three independent experiments to a commercial oligonucleotide array
      representing more than 22,000 transcripts. The resultant signal intensities and
      microarray software transcript present/absent calls were used in conjunction with
      the local pooled error (LPE) statistical method to identify transcripts that are
      preferentially or exclusively expressed in one of the two tissues at significant
      levels (expression >1% of the beta-actin level). EASE (Expression Analysis
      Systematic Explorer software) was used to identify biological systems
      comparatively overrepresented in either epithelium. Immuno-, and
      cytohistochemistry was performed to validate or expand on selected results of
      interest. RESULTS: The analysis identified 332 preferential and 93 exclusive
      significant corneal epithelial transcripts. The corresponding numbers of
      conjunctival epithelium transcripts were 592 and 211, respectively. The
      overrepresented biological processes in the cornea were related to cell adhesion
      and oxiredox equilibria and cytoprotection activities. In the conjunctiva, the
      biological processes that were most prominent were related to innate immunity and
      melanogenesis. Immunohistochemistry for antigen-presenting cells and melanocytes
      was consistent with these gene signatures. The transcript comparison identified a
      substantial number of genes that have either not been identified previously or
      are not known to be highly expressed in these two epithelia, including testican
      1, ECM1, formin, CRTAC1, and NQO1 in the cornea and, in the conjunctiva, sPLA(2)
      IIA, lipocalin 2, IGFBP3, multiple MCH class II proteins, and the Na-Pi
      cotransporter type IIb. CONCLUSIONS: Comparative gene expression profiling leads
      to the identification of many biological processes and previously unknown genes
      that are potentially active in the function of corneal and conjunctival
      epithelia.

PMID- 17460262
TI  - Corneal femtosecond laser keratotomy results in isolated stromal injury and
      favorable wound-healing response.
AB  - PURPOSE: To examine the corneal repair response after intrastromal femtosecond
      (fs) laser keratotomy. METHODS: Twelve rabbits underwent monocular intrastromal
      keratotomy performed with an fs laser at a preoperatively determined corneal
      depth of 160 to 200 microm. The fs laser-induced corneal repair response was
      compared with that of nonoperated control eyes and eyes treated with
      photorefractive keratectomy (PRK). Follow-up examinations were performed 1, 3, 7,
      and 28 days after surgery. Corneas were evaluated using slit lamp, in vivo
      confocal microscopy, and light microscopy. The extracellular matrix components
      fibronectin and tenascin were located using immunofluorescence staining. Anti-Thy
      1 and anti-alpha-SMA antibodies and phalloidin were used to identify repair
      fibroblasts. Cell proliferation and nuclear DNA fragmentation were detected using
      an anti-Ki-67 antibody and the TUNEL assay, respectively. RESULTS: Intrastromal
      fs keratotomy resulted in a hypocellular stromal scar discernible as a narrow
      band of increased reflectivity on slit lamp examination. Deposition of
      fibronectin and tenascin as well as death and subsequent proliferation of
      keratocytes were observed. No differentiation of keratocytes into Thy-1- or alpha
      SMA-positive fibroblasts could be detected. In contrast, after PRK, which causes
      epithelial and stromal wounding, all markers for repair fibroblasts were found in
      subepithelial stromal layers. On slit lamp examination, a fibrotic scar and a
      corneal haze were revealed. CONCLUSIONS: Isolated stromal injury using an fs
      laser avoids epithelial injury and is associated with a favorable wound-healing
      response preserving corneal transparency. Thus, fs laser keratotomy is a highly
      selective laser treatment that can be useful for the treatment of refractive
      errors.

PMID- 17460263
TI  - Shifts in listing's plane produced by vertical axis rotation: sustained ocular
      torsion due to semicircular canal stimulation.
AB  - PURPOSE: With the head upright and stationary, ocular torsion is confined by
      Listing's Law (LL), so that three-dimensional eye rotational axes form Listing's
      plane (LP). During head rotation, the vestibulo-ocular reflex violates LL by
      driving ocular torsion opposite to head torsion, sometimes out of LP. Saccades
      originating from non-Listing's initial torsional positions remain in a plane
      offset from, but parallel to, the original LP. The present study was conducted to
      determine whether whole-body yaw alters the position and orientation of LP.
      METHODS: Eight normal subjects and six with unilateral vestibular deafferentation
      (UVD) underwent binocular eye and head movement recordings with 3-D magnetic
      search coils. Visual fixations were used to define LP, after which subjects
      underwent whole-body yaw rotation of 30 degrees or 70 degrees , at peak
      accelerations from 125 deg/s(2) to 2800 deg/s(2). Gaze during rotation was either
      central or 20 degrees up. After rotation, a dynamic LP (DLP) was defined during
      fixations. RESULTS: Orientation and thickness of the DLP did not vary
      significantly from the previously defined LP; however, DLP was offset an average
      of 4 degrees +/- 4 degrees (mean +/- SD), 87% of head torsion relative to LP.
      Stimulus intensity, UVD, and starting vertical gaze direction had no effect on
      DLP offset or orientation. The DLP torsional offset declined toward the original
      LP with a time constant of approximately 1 minute, suggesting mediation by neural
      integration. CONCLUSIONS: Yaw rotation can cause stable torsional offsets in the
      location of Listing's Plane.

PMID- 17460264
TI  - Screening and treating amblyopia: are we making a difference?
AB  - PURPOSE: To determine the rate of amblyopia in native Jewish Israelis compared
      with those who immigrated from the former Soviet Union (U.S.S.R.) after they were
      10 years of age. METHODS: Health records of all 16-year-old subjects examined in
      the Israel Defense Forces Recruitment Center between 1998 and 2003 were analyzed.
      The number of subjects with best corrected visual acuity (BCVA) of 6/12 or less
      in at least one eye among native Israelis and among those who immigrated to
      Israel from the U.S.S.R. after they were 10 years of age was determined. Subjects
      who had any ocular disease except cataract, corneal opacity, strabismus, or
      ptosis were excluded. RESULTS: Of 305,712 subjects examined between 1998 and
      2003, 292,255 were enrolled in the study. Of those, 260,186 (89%) were born in
      Israel and 32,069 (11%) were born in the U.S.S.R. and immigrated to Israel after
      they were 10 years of age. There were 2565 (0.98%) native Israelis and 483 (1.5%)
      immigrants who had BCVA of 6/12 or less in at least one eye (chi(2) test, P <
      0.00001). The rate of amblyopia among subjects who had refractive errors was
      14.6% among immigrants, as opposed to 8.0% among native Israelis (P < 0.0001),
      whereas amblyopia rates among those with strabismus, cataract, or ptosis were
      similar in native Israelis and immigrants (34.4%, 38.6%, 12.8% as opposed to 34%,
      37.5%, 15.4%, respectively, P = 0.5-0.61). CONCLUSIONS: The difference in the
      rate of refractive amblyopia as opposed to strabismic and deprivation amblyopia
      may be due to the difference in vision screening methods between both countries.

PMID- 17460265
TI  - Infantile nystagmus adapts to visual demand.
AB  - PURPOSE: To determine the effect of visual demand on the nystagmus waveform.
      Individuals with infantile nystagmus syndrome (INS) commonly report that making
      an effort to see can intensify their nystagmus and adversely affect vision.
      However, such an effect has never been confirmed experimentally. METHODS: The eye
      movement behavior of 11 subjects with INS were recorded at different gaze angles
      while the subjects viewed visual targets under two conditions: above and then at
      resolution threshold. Eye movements were recorded by infrared oculography and
      visual acuity (VA) was measured using Landolt C targets and a two-alternative,
      forced-choice (2AFC) staircase procedure. Eye movement data were analyzed at the
      null zone for changes in amplitude, frequency, intensity, and foveation
      characteristics. Waveform type was also noted under the two conditions. RESULTS:
      Data from 11 subjects revealed a significant reduction in nystagmus amplitude (P
      < 0.05), frequency (P < 0.05), and intensity (P < 0.01) when target size was at
      visual threshold. The percentage of time the eye spent within the low-velocity
      window (i.e., foveation) significantly increased when target size was at visual
      threshold (P < 0.05). Furthermore, a change in waveform type with increased
      visual demand was exhibited by two subjects. CONCLUSIONS: The results indicate
      that increased visual demand modifies the nystagmus waveform favorably (and
      possibly adaptively), producing a significant reduction in nystagmus intensity
      and prolonged foveation. These findings contradict previous anecdotal reports
      that visual effort intensifies the nystagmus eye movement at the cost of visual
      performance. This discrepancy may be attributable to the lack of psychological
      stress involved in the visual task reported here. This is consistent with the
      suggestion that it is the visual importance of the task to the individual rather
      than visual demand per se which exacerbates INS. Further studies are needed to
      investigate quantitatively the effects of stress and psychological factors on INS
      waveforms.

PMID- 17460266
TI  - Prostaglandin FP receptors do not contribute to 24-hour intraocular pressure
      variation in mice.
AB  - PURPOSE: It is not known whether the prostaglandin FP receptor plays an important
      role in endogenous 24-hour regulation of intraocular pressure. The purpose of
      this study was to compare 24-hour intraocular pressure (IOP) in FP receptor
      knockout mice with that of wild-type mice that have normal FP receptor
      expression. METHODS: The 24-hour IOP profile was determined by rebound tonometry
      in FP-knockout and wild-type mice. Peak and trough IOP was then measured by
      microneedle cannulation of the anterior chamber in homozygous (FP(-/-); n = 8),
      heterozygous (FP(+/-); n = 14), and C57BL/6 background strain mice (FP(+/+); n =
      11). To confirm any differences in baseline IOP between genotypes, midafternoon
      IOP was also measured in a larger, separate group of FP(-/-) mice (n = 20), FP(+/
      ) mice (n = 49), and FP(+/+) (n = 23) wild-type littermates. RESULTS: Trough IOPs
      were measured between 10 AM and 12 PM, peak IOPs were measured between 8 and 10
      PM. For FP(+/+), FP(+/-), and FP(-/-) mice trough IOP was 16.2, 15.3, and 15.1 mm
      Hg and peak IOPs were 18.2, 18.4, and 17.7 mm Hg, respectively. There was no
      significant difference among genotypes for mean peak or mean trough IOP or for
      peak-trough difference in IOP among genotypes (P > 0.05, ANOVA). In addition,
      there was no significant difference in midafternoon IOP between genotypes in a
      larger population (n = 92) of FP-knockout and wild-type mice. CONCLUSIONS: An
      intact FP receptor does not appear to be critical for normal 24-hour IOP
      regulation in the mouse eye.

PMID- 17460267
TI  - Scanning laser polarimetry with enhanced corneal compensation and optical
      coherence tomography in normal and glaucomatous eyes.
AB  - PURPOSE: To examine the association between scanning laser polarimetry (SLP),
      using enhanced (ECC) and variable corneal compensation (VCC) with optical
      coherence tomography (OCT), and to compare their discriminating ability in the
      diagnosis of glaucoma. METHODS: Normal and glaucomatous eyes enrolled from four
      clinical sites underwent complete examination, automated perimetry, SLP-ECC, SLP
      VCC, and OCT. Eyes were characterized in two groups based on the typical scan
      score (TSS): Normal birefringence pattern (NBP) was defined as a TSS of 80 to 100
      and abnormal birefringence pattern (ABP) as TSS <or= 79. For each of the six SLP
      parameters and five OCT parameters the areas under the receiver operating
      characteristic curve (AUROCs) were calculated to compare the discriminating
      ability of each imaging modality, to differentiate between normal and
      glaucomatous eyes. RESULTS: Ninety-five normal volunteers and 63 patients with
      glaucoma were enrolled. Average visual field mean deviation was -4.2 +/- 4.3 dB
      in the glaucoma group. In eyes with NBP, SLP-ECC had significantly (all P <or=
      0.001) greater correlation with OCT average, superior, and inferior retinal nerve
      fiber layer (RNFL; r = 0.79, 0.67, 0.74) compared with SLP-VCC (r = 0.71, 0.43,
      0.37). In eyes with ABP, SLP-ECC had a significantly greater (all P <or= 0.001)
      correlation with OCT average, superior, and inferior RNFL (r = 0.75, 0.73, 0.83)
      compared with SLP-VCC (r = 0.51, 0.22, 0.18). The AUROC for OCT inferior average
      thickness (0.91) was similar (P = 0.26) to the TSNIT (temporal, superior, nasal,
      inferior, temporal) average obtained using SLP-ECC (0.87) and significantly (P =
      0.02) greater than SLP-VCC (0.81). CONCLUSIONS: Compared with SLP-VCC, SLP-ECC
      has significantly stronger correlations with OCT and may improve the
      discriminating ability for early glaucoma diagnosis.

PMID- 17460268
TI  - Influence of actin cytoskeletal integrity on matrix metalloproteinase-2
      activation in cultured human trabecular meshwork cells.
AB  - PURPOSE: The goal of this study was to investigate the possible link between
      actin cytoskeletal integrity and the activation of matrix metalloproteinases
      (MMPs) in trabecular meshwork (TM) cells. METHODS: Primary human TM (HTM) cells
      treated with different actin cytoskeleton-interfering agents, including
      cytochalasin D, latrunculin A, ethacrynic acid (ECA), a Rho kinase inhibitor (Y
      27632), and H-7 (serine/threonine kinase inhibitor), were examined for changes in
      actin cytoskeletal organization by phalloidin staining, MMP-2 activation by
      gelatin zymography, expression of MT1-MMP by quantitative real-time PCR analysis,
      levels of tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2), and
      activation of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular
      signal-regulated protein kinase (ERK) by immunoblotting. RESULTS: Treatment of
      HTM cells with cytochalasin D and latrunculin A led to significant activation of
      MMP-2, p38 MAPK, and ERK1/2, which appeared to correlate with changes in cell
      morphology and actin depolymerization. Additionally, treatment with these
      cytoskeleton-disrupting agents elicited increased expression of MT1-MMP in HTM
      cells, concomitant with a decrease in the levels of secreted TIMP-1 and TIMP-2.
      In contrast, treatment with ECA, Y-27632, or H-7 triggered changes in cell shape
      and reduced actin stress fibers in HTM cells but did not exert significant
      effects on MMP-2 activation or MT1-MMP expression. CONCLUSIONS: These studies
      indicate that cytochalasin D- and latrunculin A-induced alteration of actin
      cytoskeletal integrity in HTM cells is associated with MMP-2 activation, most
      likely through the upregulation of its activator, MT1-MMP. These data provide a
      mechanistic connection between actin cytoskeletal organization and MMP-2
      activation in TM cells and offer new insights into extracellular matrix
      remodeling in the aqueous outflow pathway.

PMID- 17460269
TI  - Contrast sensitivity changes due to glaucoma and normal aging: low-spatial
      frequency losses in both magnocellular and parvocellular pathways.
AB  - PURPOSE: To explore the effects of glaucoma and aging on low-spatial-frequency
      contrast sensitivity by using tests designed to assess performance of either the
      magnocellular (M) or parvocellular (P) visual pathways. METHODS: Contrast
      sensitivity was measured for spatial frequencies of 0.25 to 2 cyc/deg by using a
      published steady- and pulsed-pedestal approach. Sixteen patients with glaucoma
      and 16 approximately age-matched control subjects participated. Patients with
      glaucoma were tested foveally and at two midperipheral locations: (1) an area of
      early visual field loss, and (2) an area of normal visual field. Control subjects
      were assessed in matched locations. An additional group of 12 younger control
      subjects (aged 20-35 years) were also tested. RESULTS: Older control subjects
      demonstrated reduced sensitivity relative to the younger group for the steady
      (presumed M)- and pulsed (presumed P)-pedestal conditions. Sensitivity was
      reduced foveally and in the midperiphery across the spatial frequency range. In
      the area of early visual field loss, the glaucoma group demonstrated further
      sensitivity reduction relative to older control subjects across the spatial
      frequency range for both the steady- and pulsed-pedestal tasks. Sensitivity was
      also reduced in the midperipheral location of "normal" visual field for the
      pulsed condition. CONCLUSIONS: Normal aging results in a reduction of contrast
      sensitivity for the low-spatial-frequency-sensitive components of both the M and
      P pathways. Glaucoma results in a further reduction of sensitivity that is not
      selective for M or P function. The low-spatial-frequency-sensitive channels of
      both pathways, which are presumably mediated by cells with larger receptive
      fields, are approximately equivalently impaired in early glaucoma.

PMID- 17460270
TI  - Lack of association between interleukin-1 gene cluster polymorphisms and glaucoma
      in Chinese subjects.
AB  - PURPOSE: A recent study identified single nucleotide polymorphisms (SNPs) within
      the IL-1 gene cluster at chromosomal locus 2q13 that were associated with reduced
      risk for primary open-angle glaucoma (POAG) in whites. The purpose of this study
      was to investigate the association between IL-1 SNPs and glaucoma in Chinese
      patients with either POAG or primary-angle closure glaucoma (PACG). METHODS:
      Patients with POAG with a mean IOP without treatment that was consistently <21 mm
      Hg on diurnal testing were classified as having normal-tension glaucoma (NTG) and
      those with higher IOP were classified as having high-tension glaucoma (HTG).
      Subjects with PACG had at least 180 degrees of angle closure on gonioscopy.
      Genotypes were determined by polymerase chain reaction and restriction digest
      enzymes at the following loci: IL1A (-889C/T), IL1B (+3953C/T), and IL1B (
      511C/T). The association of individual SNPs with glaucoma was evaluated by using
      chi(2) testing. Haplotype analysis was performed with the PHASE program, with
      haplotype frequency estimated for combined cases and controls, assuming Hardy
      Weinberg equilibrium (HWE) of haplotypes. RESULTS: Of the Chinese subjects
      studies, 194 had POAG (94 NTG and 100 HTG), 125 had PACG, and 79 were normal
      control subjects. There was no significant difference in IL-1 SNP or allele
      frequencies for in subjects with POAG or PACG compared with control subjects, or
      between NTG and HTG. None of the common haplotypes showed any significant
      difference between the HTG, NTG, PACG, and normal control subjects. CONCLUSIONS:
      This study did not find an association between IL-1 gene cluster polymorphisms
      and glaucoma in this sample of Chinese subjects.

PMID- 17460271
TI  - Effect of ocular hypertension on retinal nitridergic pathway activity.
AB  - PURPOSE: Understanding the mechanisms of neuronal cell death in glaucoma is
      important for devising new treatments. Excitatory amino acids, excessive Ca(2+)
      influx, and formation of nitric oxide (NO) via NO synthase (NOS)-1 could be
      involved in glaucomatous neuropathy. The purpose of the present study was to
      examine the retinal nitridergic pathway activity in rats exposed to
      experimentally elevated intraocular pressure. METHODS: Weekly injections of HA
      were performed unilaterally in the rat anterior chamber, whereas the
      contralateral eye was injected with saline solution. At 3 or 6 weeks of
      treatment, retinal NOS activity was assessed through the conversion of (3)H-L
      arginine to (3)H-L-citrulline, whereas NOS-1, -2, and -3 levels were assessed by
      Western blotting. L-Arginine uptake was measured using (3)H-l-arginine, whereas
      mRNA levels of L-arginine transporters were determined by semiquantitative RT
      PCR. In addition, cyclic guanosine monophosphate (cGMP) levels were quantified by
      radioimmunoassay. RESULTS: At both 3 and 6 weeks of treatment, NOS activity
      significantly increased in HA-injected eyes although no changes in retinal NOS-1,
      -2, or -3 levels were observed in eyes injected with HA. L-Arginine influx and
      mRNA levels of cationic amino acid transporter type (CAT)-1 and -2 significantly
      increased in retinas from hypertensive eyes. Retinal cGMP levels significantly
      increased in eyes injected with HA for 3 but not 6 weeks. CONCLUSIONS: These
      results suggest a significant activation of the retinal nitridergic pathway in
      hypertensive eyes.

PMID- 17460272
TI  - Connective tissue structure of the tree shrew optic nerve and associated ageing
      changes.
AB  - PURPOSE: To identify the structure and composition of the tree shrew optic nerve
      to determine its potential as a model for glaucoma. METHODS: Tree shrew optic
      nerves, aged 4 weeks to 5 years, were wax or cryoembedded for analysis of overall
      morphology and cellular (glial fibrillary acidic protein [GFAP]) and
      extracellular matrix (collagen types I, III, IV, V, VI; fibronectin; and elastin)
      immunolocalization studies. In addition, transmission and scanning electron
      microscopy were performed. In vivo optic disc imaging was performed by HRT2 and
      fundus camera photography. RESULTS: The optic nerve of the tree shrew comprised
      regions comparable to the human prelaminar and lamina cribrosa (LC) in the optic
      nerve head and the retrolaminar region, immediately posterior. The multilayered
      connective tissue plates of tree shrew LC stretched across the optic nerve canal
      at the level of the sclera and consisted of collagen types I, III, IV, V, and VI;
      elastin; and fibronectin. Significant age-related alterations in connective
      tissue components were indicated. Connective tissue was present in the central
      retinal vessel sheaths and was identified as longitudinally oriented collagen
      fibrils in the retrolaminar optic nerve. GFAP immunofluorescence indicated a high
      concentration of astrocytic processes in the LC. Myelination of axons was evident
      in the retrolaminar optic nerve. Ultrastructural studies supported the structural
      organization and spatial distribution of connective tissue. CONCLUSIONS: In
      contrast to many rodent models of glaucoma, since the tree shrew optic nerve
      resembles that in humans, especially at the LC, the tree shrew offers an ideal
      opportunity to investigate glaucoma pathophysiology in a subprimate model.

PMID- 17460273
TI  - Elevated hydrostatic pressure triggers mitochondrial fission and decreases
      cellular ATP in differentiated RGC-5 cells.
AB  - PURPOSE: Mitochondrial fission is a cellular response to stress that has an
      important role in neuronal cell death in neurodegenerative diseases. The purpose
      of this study was to determine whether elevated hydrostatic pressure induces
      mitochondrial fission and dysfunction in cultured retinal ganglion cells.
      METHODS: RGC-5 cells were differentiated with succinyl concanavalin A (50
      microg/mL) and transferred to a pressurized incubator in which 30 mm Hg of
      pressure was applied for 1, 2, or 3 days. As a control, differentiated cells from
      an identical passage were incubated simultaneously in a conventional incubator at
      each of the time points. Live RGC-5 cells were then labeled with a red
      fluorescent mitochondrial dye and mitochondrial morphology was assessed by
      fluorescence microscopy and electron microscopy. After elevated hydrostatic
      pressure, the cellular adenosine triphosphate (ATP) levels were also measured by
      a luciferase-based assay. RESULTS: Mitochondrial fission, characterized by the
      conversion of tubular fused mitochondria into isolated small organelles, was
      triggered in >74.3% +/- 1.9% of mitochondria at 3 days after elevated hydrostatic
      pressure. Only 4.7% +/- 1.4% of nonpressurized control cells displayed
      mitochondrial fission after 3 days. Electron microscopy showed that elevated
      hydrostatic pressure for 3 days induced abnormal cristae depletion and decreased
      the length of the mitochondria. On elevation of hydrostatic pressure, the fission
      linked protein, Drp-1 was translocated from the cytosol to the mitochondria.
      Elevated hydrostatic pressure also resulted in a significant, time-dependent
      reduction of cellular ATP. CONCLUSIONS: Elevated hydrostatic pressure triggered
      mitochondrial fission, abnormal cristae depletion, Drp-1 translocation, and
      cellular ATP reduction in differentiated RGC-5 cells. Increased understanding of
      the molecular mechanisms that regulate the cellular response to elevated pressure
      including mitochondrial fission may provide new therapeutic targets for
      protecting RGCs from elevated hydrostatic pressure.

PMID- 17460274
TI  - The Rho-kinase inhibitor H-1152P suppresses the wound-healing activities of human
      Tenon's capsule fibroblasts in vitro.
AB  - PURPOSE: To analyze the role of Rho-kinase signaling in the wound-healing
      activities of human Tenon's capsule fibroblasts by using H-1152P, a potent
      inhibitor of this kinase, in vitro. METHODS: The optimal concentration of H-1152P
      was determined by MTT test. Cell proliferation was measured by BrdU incorporation
      and Ki-67 immunostaining, whereas cell viability was investigated by ethidium
      homodimer-1 dye exclusion. The actin cytoskeleton organization was demonstrated
      by alpha-smooth muscle actin (SMA) immunostaining and Alexa 488-phalloidin
      staining. Cell migration was studied on restrained collagen gels and in a scratch
      wound assay followed by Ki-67 and fibronectin immunostaining. The effect of H
      1152P on contraction was analyzed in floating collagen gels populated with
      fibroblasts, which were subsequently processed for fibronectin immunostaining.
      The levels of adducin and the protein kinase A (PKA)-dependent phosphorylation of
      this protein were detected by immunoblot analysis, to rule out interference with
      PKA. RESULTS: Incorporation of BrdU and upregulation of Ki-67 were reduced by 80%
      to 90% in cells incubated with 10 microM of this inhibitor for 4 days (P < 0.01).
      H-1152P caused the disassembly of stress fibers in a dose-dependent manner
      without exerting toxic effects and without a considerable interference with the
      PKA-pathway. H-1152P also significantly suppressed cell migration 3- to 3.5-fold
      and the contraction of collagen lattices fivefold with a dose-dependent
      impairment in the assembly of the fibronectin network. CONCLUSIONS: These
      findings imply a role for Rho-kinase in the wound-healing activities of human
      Tenon's capsule fibroblasts and show the potential of H-1152P as a safe and
      specific means to suppress these events.

PMID- 17460275
TI  - LYVE-1-positive macrophages are present in normal murine eyes.
AB  - PURPOSE: A functioning lymphatic system is necessary not only to permit the
      organism to mount a rapid and effective immune response but, even more so, to
      maintain tissue fluid homeostasis. However, no clear evidence of lymphatic
      vessels draining intraocular and orbital tissues--retina, choroid, sclera, and
      extraocular muscles--exists. METHODS: Ocular tissue flatmounts from normal or
      enhanced green fluorescence protein (EGFP) chimeric mice were immunostained for
      lymphatic endothelium hyaluronan receptor (LYVE-1, a routinely used lymphatic
      endothelial marker), podoplanin, Flt4/VEGFR3, Sca-1, CD11b, or F4/80 and were
      observed by confocal microscopy. Single-cell suspensions from ocular tissues were
      also prepared and were analyzed by flow cytometry. RESULTS: Lymphatic vessels
      were detected in the posterior regions of the extraocular muscles and the
      connective tissues of the extraocular muscle cones in the normal mouse. No
      typical lymphatic vessels were found within the eye. A large population of LYVE
      1(+) nonendothelial cells, distributed as single cells, was detected in all
      ocular tissues except the central cornea. These cells also express another
      lymphatic endothelial cell marker, Flt4/VEGFR3, but not podoplanin, and they have
      hyaluronan-binding ability. Bone marrow chimerism studies indicated that the LYVE
      1(+) cell populations are bone marrow derived and have a slow turnover in ocular
      tissues (3-6 months). Phenotype analysis revealed that nonendothelial LYVE
      1(+)cells in the sclera, choroid, and iris included CD11b(+)F4/80(+) macrophages,
      CD11b(+)F4/80(-) macrophages, and CD11b(-)F4/80(-) bone marrow-derived cells. All
      LYVE-1(+) cells in the retina were CD11b(+)F4/80(+) macrophages. Cells in the
      limbus and the iris root also express Sca-1, suggesting that they are
      hematopoietic lymphatic vessel progenitor cells. CONCLUSIONS: These observations
      suggest that a lymphatic system exists for the transport of immune cells and
      fluids from the posterior segment of the eye, that ocular tissues are rich in
      bone marrow-derived LYVE-1(+) macrophages under normal physiological conditions,
      and that a subpopulation of these cells may represent resident precursor cells
      necessary for the de novo formation of ocular/orbital lymphatic vessels in
      pathologic conditions.

PMID- 17460276
TI  - Bacterial transcytosis across conjunctival M cells.
AB  - PURPOSE: Antigen-sampling M cells have been identified in conjunctival tissue
      overlying lymphoid follicles in rabbits and guinea pigs. Conjunctival M cells in
      the guinea pig display alpha(2-3) sialic acid on their surfaces, as evinced by
      selective labeling by Maackia amurensis leukoagglutinin (MAL)-I. Haemophilus
      influenzae strains OM12, which expresses the HMW1 adhesin for alpha(2-3) sialic
      acid, and Rd KW20, which lacks HMW1, were used to test the hypothesis that
      conjunctival M cells translocate large microbes. METHODS: Fluorescein-labeled
      bacteria were instilled into the conjunctival sac for up to 130 minutes. Confocal
      laser scanning microscopy and electron microscopy were used to visualize
      bacterial distribution. RESULTS: M cells, but not nonfollicular epithelial cells
      in the palpebral region, selectively bound and translocated bacteria. By 66
      minutes, 423 +/- 165 bacteria/mm(2) of follicle-associated epithelial (FAE)
      surface were found in three-dimensional reconstructions extending 15.4 mum below
      the surface. By 127 minutes, the number of bacteria increased to 579 +/- 44/mm(2)
      of FAE surface and they had moved 50% deeper into the follicle. Coadministration
      with MAL-I reduced OM12 transport by 61%. Similarly, Rd KW20 uptake was 71% less
      at 63 minutes and 58% less at 121 minutes, indicating that OM12 uptake is at
      least partially mediated by binding to alpha(2-3) sialic acid. CONCLUSIONS:
      Conjunctival M cells are a port of entry for large microbes and may play a role
      in initiation of mucosal immune responses against commensal or transient ocular
      bacterial species and may allow the entry of pathogens.

PMID- 17460277
TI  - Minimally activated CD8 autoreactive T cells specific for IRBP express a high
      level of Foxp3 and are functionally suppressive.
AB  - PURPOSE: Results in previous reports have demonstrated that immunization of the
      EAU-prone B6 mouse activates both CD4 and CD8 IRBP-specific T cells. The purpose
      of this study was to investigate structural and functional differences between
      CD4 and CD8 autoreactive T cells activated by the uveitogenic peptide. METHODS:
      Purified CD4 and CD8 isolated from B6 mice immunized with an uveitogenic peptide,
      interphotoreceptor retinoid-binding protein (IRBP)1-20, were stimulated in vitro
      with various doses of immunizing peptide. The activated T cells were determined
      for cytokine production, expression of Foxp3, and suppressor activity. RESULTS:
      CD4 autoreactive T cells underwent full activation when stimulated with high or
      medium concentrations of immunizing peptide, whereas a high dose of antigenic
      peptide resulted in only modest activation of CD8 autoreactive T cells. When
      stimulated by a low dose (<0.1 microg/mL) of antigen or by of a high dose of
      antigen and a small amount of TGF-beta1, the minimally activated CD8 T cells
      expressed a high level of Foxp3 and gained suppressor function. CONCLUSIONS:
      Minimally activated CD8 autoreactive T cells can be functionally suppressive and
      may neutralize the tissue-damaging effect of the CD4 autoreactive T cells.

PMID- 17460278
TI  - Role of anti-glycoproteins D (anti-gD) and K (anti-gK) IgGs in pathology of
      herpes stromal keratitis in humans.
AB  - PURPOSE: To assess the relative impact of antibodies specific for HSV-1
      glycoproteins on eye disease in response to HSV-1 infection, the composition of
      antibodies specific for 10 of the viral glycoproteins, and the effect of anti
      glycoprotein (g)D and anti-gK antibodies on antibody-dependent enhancement (ADE).
      METHODS: In a prospective case-control study, sera from patients with a history
      of herpes stromal keratitis (HSK) were compared with sera from nonocular HSV-1
      seropositive and HSV-seronegative control subjects. HSV-1 neutralizing antibody
      titer and type-specific IgG and IgM were measured. In addition, the presence of
      anti-HSV-1 gD and gK antibodies in the sera of all patients also was determined
      by ELISA using gD and gK antigens. Finally, the role of anti-gD- and gK-specific
      antibodies to ADE was investigated. RESULTS: Average neutralizing antibody titers
      and levels of HSV-1 IgG were similar between HSK- and non-HSK-seropositive
      patients. However, the contribution of gD to the neutralizing antibody titer in
      HSK sera was significantly lower than that in non-HSK-seropositive patients,
      despite higher anti-gD ELISA titers. Overall, sera from patients with HSK had
      higher anti-gK antibody titers and induced ADE in vitro compared with non-HSK or
      seronegative sera. The ADE response in HSK sera was attributed to anti-gK
      antibody. CONCLUSIONS: These results suggest that sera from HSK patients had
      higher anti-gD and -gK antibody titers than sera from seropositive patients who
      had no history of HSK despite similar levels of neutralizing antibody titers and
      HSV-1 IgG, that HSK sera induced ADE whereas sera from non-HSK patients did not
      induce ADE, and that anti-gD antibody in sera of HSK patients contributed less to
      the HSV-1 neutralization antibody titer than did sera from non-HSK patients.

PMID- 17460279
TI  - Modulation of CD8+ CTL effector function by fibroblasts derived from the
      immunoprivileged cornea.
AB  - PURPOSE: To examine the acquisition of lytic activity and interferon gamma (IFN
      gamma) production by herpes simplex virus (HSV) type 1-specific CD8(+) cytotoxic
      T-lymphocyte precursors (HSV-CTLps) after exposure to in vitro HSV-1-infected
      fibroblasts derived from the immunoprivileged cornea (HSV-cFb) or nonprivileged
      skin (HSV-sFb) or to in vitro HSV-1-infected splenocytes (HSV-Spls) obtained from
      noninfected mice. METHODS: Chromium release assays were used to assess HSV-CTL
      cytotoxicity, and flow cytometry was used to assess intracellular granzyme (Gr) B
      content and lytic granule exocytosis through surface CD107a expression. In
      addition, the BLT esterase assay was used to assess functional GrA release.
      [(3)H]-Thymidine incorporation and total CD8(+) cell numbers, as assessed by flow
      cytometry, were used to assess CTLp proliferation. ELISA and intracellular flow
      cytometric analysis were used to assess CTL IFN-gamma production and release.
      RESULTS: HSV-cFb, HSV-sFb, and HSV-Spl individually induced strong cytotoxic and
      IFN-gamma responses by HSV-CTL. Simultaneous exposure to HSV-Spl and HSV-cFb
      virtually abrogated the cytotoxic response while enhancing IFN-gamma production
      by HSV-CTL. In contrast, exposure to HSV-sFb, in conjunction with HSV-Spl, did
      not alter the cytotoxic or IFN-gamma response of HSV-CTL compared with
      stimulation with either cell type alone. Abrogation of the cytotoxic response
      after simultaneous exposure to HSV-Spl and HSV-cFb was associated with reduced
      production, storage, or both of GrA and GrB but with unimpaired lytic granule
      release. CONCLUSIONS: These findings suggest that an interesting regulatory
      circuit protects the cornea from the potentially damaging effects of CD8(+) T
      cell cytotoxic function while maintaining their ability to control virus
      replication through enhanced production of the antiviral cytokine IFN-gamma.

PMID- 17460280
TI  - Multiplex bead analysis of vitreous humor of patients with vitreoretinal
      disorders.
AB  - PURPOSE: Vitreoretinal disorders are frequently characterized by increased
      vitreous levels of cellular mediators, including cytokines, chemokines, and
      growth factors. The study was conducted to investigate whether multiplex bead
      analysis could identify disease-specific profiles of these mediators in a variety
      of vitreoretinal diseases. METHODS: Levels of 19 mediators were measured: the
      cytokines IL-6, IL-10, IL-12, IL-13, IL-15, IL-17, TNF, IFN-gamma, granulocyte
      macrophage-colony-stimulating factor (GM-CSF), and granulocyte-stimulating factor
      (G-CSF); the chemokines CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL8; and the growth
      factors epidermal growth factor (EGF), FGF, and VEGF, by using multiplex bead
      analysis of vitreous humor of 58 eyes undergoing vitrectomy for a variety of
      vitreoretinal disorders. RESULTS: The predominant mediators detected were IL-6,
      CXCL8, and CCL2. The most complex pattern of mediators was seen in patients with
      proliferative vitreoretinopathy (PVR) and included a mixture of cytokines,
      chemokines, and growth factors. Patients with chronic uveitis showed a limited
      mediator pattern that did not suggest either a Th1 or Th2 response. By
      comparison, patients with lens-induced uveitis (LIU) showed significantly greater
      levels of cytokines than did patients with chronic uveitis, including IFN-gamma
      and IL-12, with a trend toward an acute Th1 inflammatory response. Moreover, in
      samples from patients with LIU, CXCL8 inversely correlated with time after
      initial surgery and duration of treatment. CONCLUSIONS: Multiplex bead analysis
      allows the measurement of multiple mediators from a single vitreous sample. The
      data confirm patterns of mediators previously described in different
      vitreoretinal conditions. In addition, LIU mediator levels correlate with
      duration of treatment and time after cataract surgery.

PMID- 17460281
TI  - Homozygous CRYBB1 deletion mutation underlies autosomal recessive congenital
      cataract.
AB  - PURPOSE: Some 30% of cases of congenital cataract are genetic in origin, usually
      transmitted as an autosomal dominant trait. The molecular defects underlying some
      of these autosomal dominant cases have been identified and were demonstrated to
      be mostly mutations in crystallin genes. The autosomal recessive form of the
      disease is less frequent. To date, only four genes and three loci have been
      associated with autosomal recessive congenital cataract. Two extended unrelated
      consanguineous inbred Bedouin families from southern Israel presenting with
      autosomal recessive congenital nuclear cataract were studied. METHODS: Assuming a
      founder effect, homozygosity testing was performed using polymorphic
      microsatellite markers adjacent to each of 32 candidate genes. RESULTS: A locus
      on chromosome 22 surrounding marker D22S1167 demonstrated homozygosity only in
      affected individuals (lod score > 6.57 at theta = 0 for D22S1167). Two crystallin
      genes (CRYBB1 and CRYBA4) located within 0.1 cM on each side of this marker were
      sequenced. No mutations were found in CRYBA4. However, an identical homozygous
      delG168 mutation in exon 2 of CRYBB1 was discovered in affected individuals of
      both families, generating a frameshift leading to a missense protein sequence at
      amino acid 57 and truncation at amino acid 107 of the 252-amino-acid CRYBB1
      protein. Denaturing [d]HPLC analysis of 100 Bedouin individuals unrelated to the
      affected families demonstrated no CRYBB1 mutations. CONCLUSIONS: CRYBB1 mutations
      have been shown to underlie autosomal dominant congenital cataract. The current
      study showed that a different mutation in the same gene causes an autosomal
      recessive form of the disease.

PMID- 17460282
TI  - Activation of SRC kinases signals induction of posterior capsule opacification.
AB  - PURPOSE: Posterior capsule opacification (PCO) is a complication of cataract
      surgery resulting from the proliferation, migration, and epithelial-to
      mesenchymal transition (EMT) of lens epithelial cells that remain associated with
      the lens capsule. These changes cause a loss of vision. The authors developed a
      chick embryo lens capsular bag model to study mechanisms involved in the onset of
      PCO. Because Src family kinases (SFKs) signal cell proliferation, migration, and
      EMT, the authors examined whether the inhibition of SFKs can prevent PCO.
      METHODS: After mock cataract surgery, chick lens capsular bags were pinned to a
      culture dish and grown in the presence or absence of the SFK inhibitor PP1. Cell
      movement was followed by photomicroscopy. Progression of proliferation and EMT in
      the PCO cultures was determined by Western blot analysis and immunofluorescence
      staining. RESULTS: As occurs in PCO, lens cells in this model proliferated,
      migrated across the posterior capsule, and expressed EMT markers, alpha-smooth
      muscle actin (alpha-SMA), and fibronectin (FN). Lens cells treated with PP1
      maintained an epithelial phenotype, accumulated cadherin junctions, and did not
      migrate to the posterior capsule, increase proliferation, or express EMT markers.
      Therefore, exposure to PP1 prevented PCO. Short-term inhibition of SFKs was
      sufficient to prevent EMT, but longer inhibition was necessary to prevent lens
      cell migration. CONCLUSIONS: Progression of PCO involved early activation of
      SFKs. Lens cell migration preceded EMT, and each of these two events required
      activation of an SFK signaling pathway. Suppression of SFK activation blocked
      PCO, suggesting SFKs as a therapeutic target for the prevention of PCO.

PMID- 17460283
TI  - Inhibitory effects of retinoic acid receptor alpha stimulants on murine
      cataractogenesis through suppression of deregulated calpains.
AB  - PURPOSE: To determine whether retinoic acid (RA)-mediated inhibition of
      deregulated calpains had any effect on the development of cataract given that
      accumulating evidence has demonstrated a possible relationship between
      cataractogenesis and inappropriate activation of calpains. METHODS: The authors
      examined for Ca(2+) influx and expression alteration of calpains in F9 cells with
      or without RAs, such as all-trans retinoic acid (ATRA), and specific stimulant of
      retinoic acid receptor alpha (RARalpha; Am580) in the presence of oxidative
      stress, such as mediated by H(2)O(2). They next examined the clinical relevance
      of RAs by applying these agents to a murine diabetic cataract and observed the
      development of the disease. RESULTS: F9 cells constitute a well-established
      autonomous cell model for investigating retinoid signaling, partially
      representing the lens epithelial phenotype, as determined by the expression of
      aquaporin 0, a specific differentiation marker for lens cells. Treatment with
      ATRA and Am580 significantly decreased the influx of Ca(2+) into the cells,
      causally resulting in decreased mRNA expression and inhibited activation of
      calpains. In addition, RARalpha agonists significantly abrogated the upregulation
      of calpain 2 induced by H(2)O(2), which is a potential etiological contributor to
      the diabetic cataract, whereas H(2)O(2) had no effect on calpain 1. Importantly,
      this RA-mediated gene-expression alteration was sufficient for dramatically
      inhibiting the development of lens opacity in mice with diabetes. CONCLUSIONS:
      Results showed that a certain type of RA inhibits Ca(2+) elevation and subsequent
      overactivation of calpains, suggesting the potential feasibility of calpain
      targeting therapies mediated by RA for cataract.

PMID- 17460284
TI  - Pharmacokinetics of intraocular drug delivery by periocular injections using
      ocular fluorophotometry.
AB  - PURPOSE: To evaluate the pharmacokinetics of the periocular injections: posterior
      subtenon (PST), retrobulbar (RB), and subconjunctival (SC) injection. METHODS:
      Two sodium fluorescein (NaF) concentrations, 2.5 mg in 0.1 mL (NaF1) and 2.5 mg
      in 0.5 mL (NaF2) were injected into live rabbits by the PST (NaF1 n = 4, NaF2 n =
      3), RB (NaF1 n = 10), SC (NaF1 n = 6), and intravenous (IV, NaF1 n = 6) routes
      and into euthanatized rabbits by the RB (NaF1 n = 8) route. NaF concentrations in
      the choroid/retina, vitreous, and anterior segment were measured by ocular
      fluorophotometry. The NaF level in the contralateral choroid/retina was used as a
      measure of the systemic drug levels. RESULTS: The maximum NaF concentrations
      (nanograms per milliliter) in the choroid/retina after PST, RB, SC, and IV were
      757 +/- 549 at 2 hours, 906 +/- 1014 at 1 hour, 320 +/- 462 at 2 hours, and 865
      +/- 363 at 5 to 10 minutes, respectively. The PST had the highest and most
      prolonged vitreous NaF1 concentration (maximum: 270 +/- 226 ng/mL at 3.5 hours).
      The contralateral peak choroid/retina NaF levels after the RB, SC, and IV
      injections were 7, 4, and 21 times greater than after the PST injection. The SC
      injection had the highest anterior segment NaF concentration (5364 +/- 2840 ng/mL
      at 2 hours). PST with NaF2 resulted in intraocular NaF levels higher than with
      NaF1. CONCLUSIONS: NaF reaches the choroid/retina by transscleral diffusion from
      the periocular depot. The orbital and conjunctival vasculature and lymphatics
      have a larger role in NaF clearance than does the choroid. NaF diffuses into the
      vitreous from the choroid and the anterior segment; the periocular depot location
      determines the predominant diffusion pathway. The duration of high NaF levels in
      the choroid/retina or the anterior segment determines vitreous NaF levels. PST is
      the best periocular route for vitreous NaF delivery with minimal systemic levels.
      Increasing the volume of NaF PST depot enhances transscleral drug delivery.

PMID- 17460285
TI  - Clearance of intravitreal voriconazole.
AB  - Purpose To investigate the elimination rate of voriconazole after intravitreal
      injection in rabbits. METHODS: Intravitreal injections of 35 microg/0.1 mL
      voriconazole were administered to rabbits. Vitreous and aqueous humor levels of
      voriconazole were determined at selected time intervals (1, 2, 4, 8, 16, 24, and
      48 hours), and the in vitreous half-life was calculated. Four to six eyes per
      time point after injection were enucleated and immediately stored at -80 degrees
      C. Aqueous humor samples were withdrawn before enucleation, and vitreous samples
      were obtained from ocular dissection and isolation at various time intervals.
      Voriconazole concentrations in vitreous and aqueous humor were assayed with high
      performance liquid chromatography (HPLC). RESULTS: The concentration of
      intravitreal voriconazole at various time points exhibited exponential decay with
      a half-life of 2.5 hours. The mean vitreous concentration was 18.912 +/- 2.058
      microg/mL 1 hour after intravitreal injection; this declined to 0.292 +/- 0.090
      microg/mL at 16 hours. The mean aqueous concentration was much lower and showed a
      decline from 0.240 +/- 0.051 microg/mL at 1 hour to undetectable levels 8 hours
      after injection. CONCLUSIONS: Vitreous concentrations achieved during the first 8
      hours were greater than the previously reported minimum inhibitory concentrations
      (MICs) of organisms most involved in fungal endophthalmitis. A rapid decline of
      intravitreal concentration suggests that supplementation of intraocular
      voriconazole to maintain therapeutic levels may therefore be required in clinical
      settings. Further studies are needed to determine the elimination rate of
      voriconazole after intravitreal injection in humans.

PMID- 17460287
TI  - Optical coherence tomography of the macula in congenital achromatopsia.
AB  - PURPOSE: It is known that symptoms of congenital achromatopsia are caused by the
      lack of functioning cones, but there are very few published data on histologic
      changes in the retina in these cases. This study was conducted to examine in vivo
      the anatomic structure of the retina of patients with achromatopsia. METHODS:
      Fifteen eyes of eight patients with congenital achromatopsia and 18 eyes of nine
      control subjects were examined by optical coherence tomography. Radial 6-mm scans
      were taken of the macula. The thickness of the neuroretina was measured both
      automatically and manually. Measurements were taken at the foveola and at
      distances of 1.5 and 3 mm. Total macular volume and the retinal thickness in the
      nine ETDRS regions were also calculated. RESULTS: In patients with achromatopsia,
      statistically significant reductions were found in total macular volume and in
      the thickness of the central retina. Remarkable differences were found between
      the results obtained from different methods of measuring retinal thickness.
      Automated methods underestimated retinal thickness compared with manual
      measurements. CONCLUSIONS: The structure of the macula in achromats differs from
      that in normal subjects. A possible reason for the structural alteration is the
      qualitative and/or quantitative disorder of the cone photoreceptors, as the
      morphologic change is most expressed in the foveola. The automated methods are
      not always suitable for measuring retinal thickness in the foveola. The
      structural changes seen in the central retina of the patients could provide
      useful information for future gene therapy.

PMID- 17460286
TI  - Cross talk between c-Met and epidermal growth factor receptor during retinal
      pigment epithelial wound healing.
AB  - PURPOSE: The authors sought to determine how hepatocyte growth factor (HGF)
      receptor c-Met and epidermal growth factor receptor (EGFR) cross talk in response
      to injury in human ARPE-19 cells. METHODS: A scratch wound was made on a cell
      monolayer of ARPE-19 cells using a sequence-comb or a pipet tip, and it was
      allowed to heal in the presence or absence of HGF and heparin-binding EGF-like
      growth factor (HB-EGF). The activation of EGFR was analyzed by
      immunoprecipitation with EGFR antibody, followed by Western blotting with
      phosphotyrosine-specific antibody. Phosphorylation of extracellular signal
      regulated kinase (ERK) and AKT (a major substrate of phosphatidylinositol 3'
      kinase (PI3K) was assessed by Western blotting. The release of c-Met ectodomain
      into the culture media was determined by Western blotting using an antibody
      against the extracellular region. Cell migration was assessed by Boyden chamber
      migration assay. RESULTS: ARPE-19 cells underwent spontaneous wound healing in
      basal medium, and exogenously added HB-EGF and HGF significantly enhanced wound
      closure. Basal and growth factor-enhanced wound closures were attenuated but not
      slowed by hydroxyurea, a cell proliferation inhibitor. RPE cells expressed all
      four erbBs, and wounding induced EGFR transactivation and downstream ERK and PI3K
      phosphorylation in ARPE-19 cells. HGF also induced EGFR tyrosine phosphorylation.
      The EGFR kinase inhibitor AG1478 blocked wound- and HGF-stimulated EGFR
      transactivation and attenuated spontaneous and growth factor-induced wound
      closure. Wounding and EGFR ligands induced the release of c-Met into the culture
      media. Moreover, pretreatment of cells with HB-EGF impaired ARPE-19 migration
      toward HGF in a matrix metalloproteinase inhibitor-sensitive manner. CONCLUSIONS:
      EGFR modulates HGF/c-Met activity by inducing c-Met ectodomain shedding, and
      HGF/c-Met transactivates EGFR, leading to an enhanced activation of downstream
      signaling pathways. Cross talk between EGFR and c-Met may play a key role in
      regulating RPE cell migration, proliferation, and wound healing.

PMID- 17460288
TI  - Correlation between focal macular electroretinograms and angiographic findings
      after photodynamic therapy.
AB  - PURPOSE: It is known that the amplitudes of the multifocal electroretinograms are
      generally reduced soon after photodynamic therapy (PDT). The purpose of this
      study was to determine whether this amplitude reduction correlates with the
      changes in macular thickness or with changes in choroidal circulation. METHODS:
      Thirty-seven eyes that were successfully treated by PDT were studied. Focal
      macular electroretinograms (fmERGs) and optical coherence tomography were
      performed before and 1 week, 1 month, and 3 months after PDT. Indocyanine green
      angiography was performed before and 3 months after PDT. The indocyanine green
      angiographic findings were classified into two groups: group A, with indistinct
      hypofluorescence at the site of the PDT, and group B, with well-defined
      hypofluorescence borders coinciding with the site of the PDT. RESULTS: The mean
      amplitudes of the fmERGs were significantly reduced at 1 week after PDT (P <
      0.05). The correlations between the changes in the amplitude of the fmERG and the
      changes in macular thickness were not significant. Sixteen (43%) of the study
      eyes were classified into group A and 21 (57%) into group B by indocyanine green
      angiography. The mean ratio of the fmERG b-wave 1 week after PDT to that before
      PDT was 1.14 +/- 0.62 in group A and 0.65 +/- 0.29 in group B. This difference
      was statistically significant (P < 0.01). CONCLUSIONS: One of the possibilities
      that could explain the reduction in the amplitude of the fmERGs soon after PDT is
      the reduction in choroidal circulation caused by the PDT.

PMID- 17460289
TI  - Automated detection and differentiation of drusen, exudates, and cotton-wool
      spots in digital color fundus photographs for diabetic retinopathy diagnosis.
AB  - PURPOSE: To describe and evaluate a machine learning-based, automated system to
      detect exudates and cotton-wool spots in digital color fundus photographs and
      differentiate them from drusen, for early diagnosis of diabetic retinopathy.
      METHODS: Three hundred retinal images from one eye of 300 patients with diabetes
      were selected from a diabetic retinopathy telediagnosis database (nonmydriatic
      camera, two-field photography): 100 with previously diagnosed bright lesions and
      200 without. A machine learning computer program was developed that can identify
      and differentiate among drusen, (hard) exudates, and cotton-wool spots. A human
      expert standard for the 300 images was obtained by consensus annotation by two
      retinal specialists. Sensitivities and specificities of the annotations on the
      300 images by the automated system and a third retinal specialist were
      determined. RESULTS: The system achieved an area under the receiver operating
      characteristic (ROC) curve of 0.95 and sensitivity/specificity pairs of 0.95/0.88
      for the detection of bright lesions of any type, and 0.95/0.86, 0.70/0.93, and
      0.77/0.88 for the detection of exudates, cotton-wool spots, and drusen,
      respectively. The third retinal specialist achieved pairs of 0.95/0.74 for bright
      lesions and 0.90/0.98, 0.87/0.98, and 0.92/0.79 per lesion type. CONCLUSIONS: A
      machine learning-based, automated system capable of detecting exudates and cotton
      wool spots and differentiating them from drusen in color images obtained in
      community based diabetic patients has been developed and approaches the
      performance level of retinal experts. If the machine learning can be improved
      with additional training data sets, it may be useful for detecting clinically
      important bright lesions, enhancing early diagnosis, and reducing visual loss in
      patients with diabetes.

PMID- 17460290
TI  - Reduced photoreceptor damage after photodynamic therapy through blockade of
      nitric oxide synthase in a model of choroidal neovascularization.
AB  - PURPOSE: To investigate the role of nitric oxide synthase (NOS) in photoreceptor
      degeneration associated with photodynamic therapy (PDT) in a laser-induced model
      of choroidal neovascularization (CNV). METHODS: PDT was performed in monkey and
      Brown Norway rats with laser-induced CNV. L-NAME, a NOS inhibitor, or saline was
      injected intraperitoneally in rats with CNV. An NO donor, or saline, was injected
      intravitreously into normal rats. Photoreceptor apoptosis was evaluated by TUNEL
      and electron microscopy. NOS, ED-1, and cleaved-caspase-3 (c-casp-3) expression
      were determined by immunohistochemistry. CNV lesions were examined by
      fluorescence angiography and choroidal flat mount. RESULTS: TUNEL and electron
      microscopy showed photoreceptor apoptosis after PDT. In rats, there were
      significantly more TUNEL-positive cells in the photoreceptors 24 hours after PDT,
      whereas in the CNV lesions there were more TUNEL-positive cells 6 hours after
      PDT. C-casp-3 was detected in the CNV lesions but not in the photoreceptors after
      PDT. There was no difference in the numbers of ED-1-positive macrophages before
      and after PDT. However, inducible NOS (iNOS) was increased after PDT in
      macrophages. Intravitreous injection of the NO donor without PDT also induced
      substantial photoreceptor apoptosis. L-NAME-treated animals had significantly
      fewer TUNEL-positive cells in the photoreceptors than saline-treated animals
      after PDT (P < 0.05). There were no differences in CNV size and leakage between L
      NAME- and saline-treated groups. CONCLUSIONS: iNOS expression in macrophages
      contributes to PDT-induced photoreceptor degeneration. NOS inhibition reduces PDT
      induced photoreceptor degeneration without compromising the treatment effect of
      PDT in an experimental model of CNV.

PMID- 17460291
TI  - IDOCS: intelligent distributed ontology consensus system--the use of machine
      learning in retinal drusen phenotyping.
AB  - PURPOSE: To use the power of knowledge acquisition and machine learning in the
      development of a collaborative computer classification system based on the
      features of age-related macular degeneration (AMD). METHODS: A vocabulary was
      acquired from four AMD experts who examined 100 ophthalmoscopic images. The
      vocabulary was analyzed, hierarchically structured, and incorporated into a
      collaborative computer classification system called IDOCS. Using this system,
      three of the experts examined images from a second set of digital images compiled
      from more than 1000 patients with AMD. Images were annotated, and features were
      identified and defined. Decision trees, a machine learning method, were trained
      on the data collected and used to extract patterns. Interrelationships between
      the data from the different clinicians were investigated. RESULTS: Six drusen
      classes in the structured vocabulary were largely sufficient to describe all the
      identified features. The decision trees classified the data with 76.86% to 88.5%
      accuracy and distilled patterns in the form of hierarchical trees composed of 5
      to 15 nodes. Experts were largely consistent in their characterization of soft,
      and to a lesser extent, hard drusen, but diverge in definition of other drusen.
      Size and crystalline morphology were the main determinants of drusen type across
      all experts. CONCLUSIONS: Machine learning is a powerful tool for the
      characterization of disease phenotypes. The creation of a defined feature set for
      AMD will facilitate the development of an IDOCS-based classification system.

PMID- 17460292
TI  - Retinal abnormalities in early Alzheimer's disease.
AB  - PURPOSE: There is evidence suggesting that visual disturbances in patients with
      Alzheimer's Disease (AD) are due to pathologic changes in the retina and optic
      nerve, as well as to higher cortical impairment. The purpose of this study was to
      evaluate retinal hemodynamic parameters and to characterize patterns of retinal
      nerve fiber layer (RNFL) loss in patients with early AD. METHODS: Nine patients
      with mild to moderate probable AD (mean Mini Mental State Examination score 24 of
      a possible 30 (age 74.3 +/- 3.3 years; mean +/- SD) and eight age-matched control
      subjects (age, 74.3 +/- 5.8 years) were included in this prospective cross
      sectional study. Blood column diameter, blood velocity, and blood flow rate were
      measured in the major superior temporal retinal vein in each subject by using a
      laser Doppler instrument. Peripapillary RNFL was measured by optical coherence
      tomography. RESULTS: Patients with AD showed a significant narrowing of the
      venous blood column diameter (131.7 +/- 10.8 microm) compared with control
      subjects (148.3 +/- 12.7 microm, P = 0.01), and a significantly reduced venous
      blood flow rate (9.7 +/- 3.1 microL/min) compared with the control subjects (15.9
      +/- 3.7 microL/min, P = 0.002). A significant thinning of the RNFL was found in
      the superior quadrant in patients with AD (92.2 +/- 21.6 microm) compared with
      control subjects (113.6 +/- 10.7 microm, P = 0.02). There were no significant
      differences in the inferior, temporal, or nasal RNFL thicknesses between the
      groups. CONCLUSIONS: Retinal abnormalities in early AD include a specific pattern
      of RNFL loss, narrow veins, and decreased retinal blood flow in these veins. The
      results show that AD produces quantifiable abnormalities in the retina.

PMID- 17460293
TI  - Intraretinal oxygen distribution and consumption during retinal artery occlusion
      and graded hyperoxic ventilation in the rat.
AB  - PURPOSE: To determine intraretinal oxygen distribution and consumption in a rat
      model of retinal artery occlusion during air breathing and stepwise systemic
      hyperoxia. METHODS: Laser occlusion of the pair of retinal arteries feeding the
      area of retina under investigation was performed. Oxygen-sensitive
      microelectrodes were then used to measure oxygen tension as a function of depth
      through the retina. Breathing mixtures were manipulated to produce stepwise
      increments in systemic oxygen levels, and the measurement of intraretinal oxygen
      distribution was repeated. Oxygen distribution in the retina was analyzed by an
      established eight-layer mathematical model of retinal oxygen consumption.
      RESULTS: Intraretinal oxygen distribution in the occluded area confirmed that the
      choroid was the only source of retinal oxygenation. Under air-breathing
      conditions, the oxygen supply from the choroid was sufficient to support the
      photoreceptor inner segments. Any remaining oxygen was consumed by the outer
      plexiform layer. Increases in inspired oxygen level reduced the extent of inner
      retinal anoxia. However, some degree of anoxia in the innermost retina was
      usually present. CONCLUSIONS: Occlusion of the retinal circulation renders most
      of the inner retina anoxic. Ventilation with 100% oxygen does not generally avoid
      some degree of intraretinal anoxia. With 100% oxygen ventilation, the oxygen
      consumption of the inner retina was more than four times that of the outer
      retina. A marked degree of heterogeneity in oxygen uptake of different retinal
      layers was evident. The dominant oxygen consumers were the inner segments of the
      photoreceptors, the outer plexiform layer, and the inner plexiform layer.

PMID- 17460294
TI  - High-resolution in vivo imaging of the RPE mosaic in eyes with retinal disease.
AB  - PURPOSE: To use high-resolution and contrast imaging techniques to reveal
      microscopic retinal structures, including individual retinal pigment epithelial
      (RPE) cells, in human eyes with inherited retinal disease. METHODS: Adaptive
      optics scanning laser ophthalmoscopy (AOSLO) was used to image the macular region
      in patients with retinal degenerative diseases, including two patients with cone
      rod dystrophy and one with bilateral progressive maculopathy. Images were
      processed, and the microscopic details were analyzed. Fundus-related
      microperimetry was used to assess visual function within retinal regions where no
      cones were visible. RESULTS: In addition to patches of intact cone
      photoreceptors, AOSLO images revealed mosaics of RPE cells in regions where it
      appeared that cones were missing. In cone-rod dystrophy (CRD), the RPE cells were
      visualized in an annular region surrounding a cone-preserved central area. RPE
      cell shape, size, and distribution compared well with measurements from the
      literature. Fundus-related microperimetry results indicated scotomas that
      corresponded to the locations where RPE cells were visible. CONCLUSIONS: For the
      first time, the mosaic of RPE cells has been directly visualized by AOSLO.
      Patients with hereditary retinal degenerations causing cone loss in the macula
      allowed visualization of RPE cells in areas where cones were missing. Regions
      with visible RPE cells demonstrated loss of visual function measured using
      microperimetry.

PMID- 17460295
TI  - Neuron stress and loss following rodent anterior ischemic optic neuropathy in
      double-reporter transgenic mice.
AB  - PURPOSE: Nonarteritic anterior ischemic optic neuropathy (NAION) is an optic
      nerve infarct involving axons of retinal ganglion cell (RGC) neurons. The rodent
      NAION model (rAION) can use transgenic mouse strains to reveal unique
      characteristics about the effects of sudden optic nerve ischemia on RGCs and
      their axons. The impact of rAION on RGC stress patterns, RGC loss, and their
      axons after axonal infarct were evaluated. METHODS: A double-transgenic mouse
      strain was used, containing a construct with cyan fluorescent protein (CFP) under
      Thy-1 promoter control, and a construct with beta-galactosidase (lacZ) linked to
      the stress gene c-fos promoter. Thy-1 in the retina is expressed predominantly in
      RGCs, enabling stereologic analysis of CFP(+) RGC numbers and loss post-rAION
      using confocal microscopy. RGC loss was correlated with axonal counts using
      transmission electron microscopy (TEM). LacZ immunohistochemistry was used to
      evaluate retinal cell stress after rAION. RESULTS: The 45,000 CFP(+) cells in the
      RGC layer of control animals compared with previous RGC quantitative estimates.
      rAION produced RGC stress, defined as lacZ expression, in patterns corresponding
      with later RGC loss. rAION-associated RGC loss correlated with regional nerve
      fiber layer loss. Axonal loss correlates with stereologically determined RGC loss
      estimates in transgenic mice retinas. CONCLUSIONS: Post-ON infarct RGC stress
      patterns correlate with regional RGC loss. Cellular lacZ levels in most RGCs are
      low, suggesting rAION-affected RGCs express c-fos only transiently. CFP(+) cell
      loss correlates closely with quantitative axonal loss, suggesting that the Thy-1
      (CFP) transgenic mouse strain is appropriate for RGC stereologic analyses.

PMID- 17460296
TI  - Neuroprotection in the juvenile rat model of light-induced retinopathy: evidence
      suggesting a role for FGF-2 and CNTF.
AB  - PURPOSE: In a former study, it was demonstrated that the retina of juvenile
      Sprague-Dawley (SD) rat has a remarkable intrinsic resistance to light-induced
      retinopathy compared with the adult retina. The purpose of the present study was
      to investigate the cellular and molecular mechanisms underlying this endogenous
      resistance to light-induced damage. METHODS: Juvenile SD rats were exposed for 6
      (from P14 to P20) or 14 (from P14 to P28) days to a bright, cyclic, luminous
      environment of 10,000 lux. Retinal histology was examined immediately after
      exposure to light or at 2 months of age, and photoreceptor cell death was
      quantified by measuring the thickness of the outer nuclear layer (ONL) and by
      TUNEL assays. Changes in protein levels and cellular localization of fibroblast
      growth factor (FGF)-2, ciliary neurotrophic factor (CNTF), and brain-derived
      neurotrophic factor (BDNF) were determined by Western blot analysis and retinal
      immunohistochemistry, respectively. RESULTS: The data demonstrate that although
      the rate of photoreceptor loss was different after 6 and 14 days of exposure to
      light, similar ONL thickness was reached at 2 months of age--that is, 4 to 5
      weeks after exposure to light. A large number of TUNEL-positive photoreceptors
      was visualized immediately after 6 and 14 days of exposure to light, reflecting
      the intense cell death that was occurring in the ONL. Western blot analysis
      showed that exposure to light induced a strong upregulation of the neurotrophic
      factors FGF-2 and CNTF in juvenile retinas, whereas no change in BDNF protein
      expression was noted. Of interest, after exposure to light, endogenous FGF-2 and
      CNTF were selectively upregulated in Muller cells. CONCLUSIONS: The results show
      that endogenous expression of FGF-2 and CNTF by Muller glia may play a role in
      protecting the juvenile retina from light-induced damage.

PMID- 17460297
TI  - Suppression of choroidal neovascularization by inhibiting angiotensin-converting
      enzyme: minimal role of bradykinin.
AB  - PURPOSE: Angiotensin-converting enzyme (ACE), also known as kininase II,
      functions not only to convert angiotensin I to angiotensin II, but also to cleave
      bradykinin into inactive fragments. Thus, ACE inhibition causes the tissue
      accumulation of bradykinin, exerting either of two opposite effects: anti- or
      proangiogenic. The purpose of the present study was to investigate the role of
      bradykinin in the development of choroidal neovascularization (CNV), with or
      without ACE inhibition. METHODS: Laser photocoagulation was used to induce CNV in
      wild-type C57BL/6J mice and angiotensin II type 1 receptor (AT1-R)-deficient
      mice. Wild-type mice were pretreated with the ACE inhibitor imidapril, with or
      without the bradykinin B2 receptor (B2-R) antagonist icatibant daily for 6 days
      before photocoagulation, and the treatment was continued daily until the end of
      the study. CNV response was analyzed by volumetric measurements using confocal
      microscopy 1 week after laser injury. The mRNA and protein levels of vascular
      endothelial growth factor (VEGF), intercellular adhesion molecule (ICAM)-1, and
      monocyte chemotactic protein (MCP)-1 in the retinal pigment epithelium-choroid
      complex were examined by RT-PCR and ELISA, respectively. RESULTS: ACE inhibition
      led to significant suppression of CNV development to the level seen in AT1-R
      deficient mice. B2-R blockade together with high-dose but not low-dose ACE
      inhibition resulted in more potent suppression of CNV than did ACE inhibition
      alone. B2-R blockade alone exhibited little or no effect on CNV. VEGF, ICAM-1,
      and MCP-1 levels, elevated by CNV induction, were significantly suppressed by ACE
      inhibition. VEGF but not ICAM-1 or MCP-1 levels were further attenuated by B2-R
      blockade with ACE inhibition. CONCLUSIONS: These results suggest a limited
      contribution of the kallikrein-kinin system to the pathogenesis of CNV, in which
      the renin-angiotensin system plays more essential roles for facilitating
      angiogenesis. The present study indicates the possibility of ACE inhibition as a
      novel therapeutic strategy to inhibit CNV.

PMID- 17460298
TI  - Calcitriol is a potent inhibitor of retinal neovascularization.
AB  - PURPOSE: Vitamin D compounds inhibit the growth of a variety of tumors in
      preclinical and clinical studies. Among the mechanisms suggested for this
      inhibition is antiangiogenesis. Retinal angiogenesis is the basis for vision loss
      in several major blinding diseases. The purpose of this study was to evaluate the
      antiangiogenic activity of calcitriol (1,25-dihydroxyvitamin D(3)) in vivo and
      its effect on retinal endothelial cell (EC) proliferation, migration, and
      capillary morphogenesis in vitro. METHODS: The mouse oxygen-induced ischemic
      retinopathy (OIR) model was used to assess the antiangiogenic activity of
      calcitriol. Ocular VEGF levels were determined by Western blot analysis of whole
      eye extracts from postnatal day (P) 15 mice during OIR. The effects of calcitriol
      on retinal EC proliferation, migration, and capillary morphogenesis were also
      assessed in vitro. RESULTS: Calcitriol-treated animals demonstrated a significant
      decrease in retinal neovascularization compared with control animals. This effect
      was dose dependent, and retinal neovascularization was significantly inhibited in
      calcitriol-treated mice. Although no deaths occurred, calcitriol administration
      was associated with increased serum calcium and a lack of increase in body weight
      in a dose-independent manner. The ocular level of VEGF was similar in control and
      calcitriol-treated animals. At a lower concentration of calcitriol, retinal EC
      capillary morphogenesis in solubilized basement membrane was inhibited without a
      significant inhibitory effect on EC proliferation and migration. The
      concentration of calcitriol required to inhibit retinal EC proliferation was
      significantly higher than that required to inhibit EC capillary morphogenesis.
      CONCLUSIONS: These data suggest calcitriol is a potent inhibitor of retinal
      neovascularization and may be of benefit in the treatment of a variety of eye
      diseases with a neovascular component.

PMID- 17460299
TI  - A potential role for PDGF-C in experimental and clinical proliferative
      vitreoretinopathy.
AB  - PURPOSE: Proliferative vitreoretinopathy (PVR) is a disorder characterized by the
      formation of cellular membranes on both surfaces of the retina and within the
      vitreous cavity. It occurs in 5% to 10% of patients who undergo retinal
      reattachment surgery. In the rabbit model of the disease, the platelet-derived
      growth factor alpha receptor (PDGFRalpha) is dramatically more capable of
      promoting PVR than is closely related PDGFRbeta. To test the ligand hypothesis
      (i.e., that this phenomenon can be explained by a predominance of PDGFRalpha
      specific ligands) this study was conducted to determine the profile of PDGF
      ligands expressed by cells that induce PVR and in the vitreous of rabbits that
      have PVR. In addition, we examined which PDGF isoforms were present in the
      vitreous of patients with PVR, to assess the relevance of the rabbit model to the
      clinical setting. METHODS: PDGF isoforms were detected and quantified by Western
      blot analysis and ELISA. An assay was performed of conditioned medium from mouse
      embryo fibroblasts expressing the PDGFRalpha (Falpha) and rabbit conjunctival
      fibroblasts (RCFs), both of which cause PVR in the experimental model, and from
      human retinal pigment epithelial cells (ARPE-19). Because PDGF-C is secreted in a
      latent form and must be proteolytically processed to become biologically active,
      a PDGF-C processing assay was established, and conditioned medium was tested from
      these cells lines, for processing activity. Vitreous specimens, from control and
      PVR rabbits and from patients undergoing vitrectomy surgery, either to repair
      retinal detachment or for other reasons, were also tested for PDGF isoforms and
      for PDGF-C processing activity. RESULTS: PDGF isoforms that activate PDGFRbeta
      (PDGF-B and -D) were either undetectable or were present at very low levels in
      all the samples tested. Relatively low levels of PDGF-A and -AB were detected,
      whereas PDGF-C was the predominant isoform. Falpha, RCFs, and ARPE-19 cells
      accumulated PDGF-C in the conditioned medium at an average rate of 2.0 +/- 0.2,
      2.9 +/- 0.3, and 71.3 +/- 6.0 ng/mL per day, respectively. Although there was no
      detectable PDGF-C in the vitreous of control rabbits (n = 8), there was an
      average of 1784 +/- 1150 ng/mL latent PDGF-C in the vitreous from rabbits with
      PVR (n= 14). Of the patients with PVR, eight of nine contained PDGF-C (range, 50
      1000 ng/mL). In contrast, PDGF-C was detected in only 1 of 16 of the patients
      without PVR. In both conditioned medium and vitreous samples, the latent (instead
      of the active) form of PDGF-C was detected, even though processing activity was
      present in all the samples tested. CONCLUSIONS: The predominance of PDGF isoforms
      that activate PDGFRalpha support the ligand hypothesis as an explanation of why
      PDGFRalpha is more capable of inducing PVR than is PDGFRbeta. Furthermore, the
      profile of PDGF isoforms observed in the rabbit model accurately reflected the
      clinical specimens from patients with PVR. Finally, these findings implicate one
      of the new PDGF family members as an important contributor to experimental and
      clinical PVR.

PMID- 17460300
TI  - Bilberry (Vaccinium myrtillus) anthocyanins modulate heme oxygenase-1 and
      glutathione S-transferase-pi expression in ARPE-19 cells.
AB  - PURPOSE: To determine whether anthocyanin-enriched bilberry extracts modulate pre
      or posttranslational levels of oxidative stress defense enzymes heme-oxygenase
      (HO)-1 and glutathione S-transferase-pi (GST-pi) in cultured human retinal
      pigment epithelial (RPE) cells. METHODS: Confluent ARPE-19 cells were
      preincubated with anthocyanin and nonanthocyanin phenolic fractions of a 25%
      enriched extract of bilberry (10(-6)-1.0 mg/mL) and, after phenolic removal,
      cells were oxidatively challenged with H(2)O(2). The concentration of
      intracellular glutathione was measured by HPLC and free radical production
      determined by the dichlorofluorescin diacetate assay. HO-1 and GST-pi protein and
      mRNA levels were determined by Western blot and RT-PCR, respectively. RESULTS:
      Preincubation with bilberry extract ameliorated the intracellular increase of
      H(2)O(2)-induced free radicals in RPE, though H(2)O(2) cytotoxicity was not
      affected. By 4 hours, the extract had upregulated HO-1 and GST-pi protein by 2.8-
      and 2.5-fold, respectively, and mRNA by 5.5- and 7.1-fold, respectively, in a
      dose-dependent manner. Anthocyanin and nonanthocyanin phenolic fractions
      contributed similarly to mRNA upregulation. CONCLUSIONS: Anthocyanins and other
      phenolics from bilberry upregulate the oxidative stress defense enzymes HO-1 and
      GST-pi in RPE, suggesting that they stimulate signal transduction pathways
      influencing genes controlled by the antioxidant response element.

PMID- 17460301
TI  - Loss of insulin-mediated vasoprotection: early effect of diabetes on pericyte
      containing microvessels of the retina.
AB  - PURPOSE: Microvascular cell death is a prominent pathologic feature of the
      retinopathy associated with insulin-deficient diabetes. The aim of this study was
      to test the hypothesis that reduced insulin action may contribute to
      microvascular damage in the diabetic retina. METHODS: Microvascular complexes
      were isolated from retinas of healthy rats and those made insulin deficient by
      streptozotocin. As a model of ischemia, freshly isolated microvessels were
      maintained in a glucose-free, low-oxygen solution. Cell viability in pericyte
      containing retinal microvessels was assayed by trypan blue dye exclusion. Cleaved
      caspase-3 immunoreactivity and nuclear morphology were used to detect apoptotic
      cells. RESULTS: Ischemia significantly increased apoptotic cell death in pericyte
      containing microvessels of the normal rat retina. In a dose-dependent (IC(50) =
      600 pM) manner, physiological concentrations of insulin markedly decreased
      ischemic cell death in the retinal microvasculature. This insulin-mediated
      vasoprotection was prevented by inhibitors of phosphatidylinositol-3-OH kinase
      and extracellular signal-regulated kinase. Soon after the onset of diabetes,
      insulin failed to significantly diminish cell death in ischemic retinal
      microvessels, in contrast to the prosurvival effect of this hormone on
      nondiabetic microvessels. CONCLUSIONS: Results of this study support the
      hypothesis that a physiological concentration of insulin exerts a prosurvival
      effect on ischemic retinal microvessels and that diabetes impairs the ability of
      insulin to protect against ischemia-induced microvascular cell death. The authors
      propose that the loss of insulin-mediated vasoprotection may be a previously
      unappreciated mechanism by which diabetic retinopathy progresses.

PMID- 17460302
TI  - Neuroprotective effect of transcorneal electrical stimulation on the acute phase
      of optic nerve injury.
AB  - PURPOSE: Traumatic optic neuropathy often induces a loss of vision that proceeds
      rapidly within several hours, together with retinal ganglion cell death, in a
      much slower time course. Electrical stimulation has previously been shown to
      rescue injured retinal ganglion cells from cell death. The present study tests
      whether transcorneal electrical stimulation could preserve visual function after
      an optic nerve crush. METHODS: Transcorneal electrical stimulation was given
      immediately after a calibrated optic nerve crush. We measured visually evoked
      potentials (VEPs) in the visual cortex of rats before and immediately after the
      optic nerve crush and after the transcorneal stimulation to estimate an extent of
      damage and effects of stimulation in individual animals. In addition, the retinal
      axons were labeled with a fluorescent anterograde tracer to determine whether the
      transcorneal electrical stimulation can protect the retinal axons from
      degeneration. RESULTS: The optic nerve crush was made at an intensity that does
      not allow a spontaneous recovery of VEP for 1 week. The transcorneal stimulation
      immediately increased VEP amplitude impaired by the optic nerve crush, and this
      augmentation was often preserved after 1 week. In the stimulated animals, a
      larger amount of retinal axons projected centrally beyond the crushed region in
      comparison to the unstimulated animals. CONCLUSIONS: Transcorneal electrical
      stimulation would restore the functional impairment of optic nerve by traumatic
      injury at a very early stage and protect retinal axons from the ensuing
      degeneration.

PMID- 17460303
TI  - Male prevalence of acquired color vision defects in asymptomatic carriers of
      Leber's hereditary optic neuropathy.
AB  - PURPOSE: Leber's hereditary optic neuropathy (LHON) is a maternally inherited
      disease resulting in loss of central vision and dyschromatopsia, caused by
      mitochondrial DNA point mutations. However, only a subset of the mutation
      carriers becomes affected, with a higher penetrance in males. This study was
      conducted to investigate chromatic losses in asymptomatic carriers of the LHON
      mutation. METHODS: Monocular chromatic discrimination was studied with the
      Cambridge Colour Test (CCT; Cambridge Research Systems, Ltd., Rochester, UK)
      along the protan, deutan, and tritan cone isolation axes in 46 LHON carriers (15
      men) belonging to the same LHON maternal lineage and 74 age-matched control
      subjects (39 men). Inclusion criteria were absence of ophthalmic complaints and
      clear ocular media. A detailed neuro-ophthalmic examination was performed in all
      the LHON carriers. RESULTS: The differences in threshold between carriers and
      control subjects were significant for the three cone isolation axes at P <
      0.0001. Sixty-five percent of the carriers had abnormal protan and/or deutan
      thresholds; some of those with higher thresholds also had elevated tritan
      thresholds (13%). The male thresholds were higher and more frequent than those of
      the women for the protan and deutan axes (ANOVA; P < 0.05), but not for tritan
      thresholds. In the most severe losses, the women had instances of diffuse defect
      whereas all the men displayed a red-green defect. CONCLUSIONS: Male LHON
      asymptomatic carriers had color vision losses with the red-green pattern of
      dyschromatopsia typical of patients affected with LHON, which includes elevation
      of tritan thresholds as well. This predominantly parvocellular (red-green)
      impairment is compatible with the histopathology of LHON, which affects mostly
      the papillomacular bundle. In contrast with male losses, female losses were less
      frequent and severe. These gender differences are relevant to understanding LHON
      pathophysiology, suggesting that hormonal factors may be of great importance.

PMID- 17460304
TI  - The effect of myopia on contrast thresholds.
AB  - PURPOSE: To examine the relationship between the degree of myopia and foveally
      measured contrast thresholds. METHODS: Monocular thresholds for positive and
      negative contrast were obtained from 60 myopes (-1.0 to -8.0 D) and 20 emmetropes
      of similar age. The contrast thresholds were measured at different background
      luminance levels, photopic and mesopic, by using a visual stimulus generator and
      a staircase METHOD: Against a gray background, light (dark) letters were used to
      study positive (negative) contrast. ANOVA was used to identify factors
      influencing the contrast sensitivity. For the myopes, the contrast thresholds
      were regressed against the spherical equivalent refractive error, accounting for
      different intercepts and slopes between positive and negative contrasts. RESULTS:
      Myopes yielded lower sensitivity to contrast than did emmetropes and, in contrast
      to emmetropes, exhibited higher contrast thresholds for negative than for
      positive contrast in both photopic and mesopic conditions. At all background
      luminance levels, contrast thresholds of myopic subjects increased systematically
      with a higher spherical equivalent refractive error, and the rate of increase was
      higher for negative than for positive contrast. The regression models yielded
      adjusted coefficients of determination (R(2)(adj)) of 0.735 and higher.
      CONCLUSIONS: Despite having corrected visual acuity, myopes exhibited reduced
      sensitivity to contrast in comparison to emmetropes. Furthermore, the contrast
      sensitivity decreased with an increasing degree of myopia, and the rate of
      decline was higher for negative than for positive contrast.

PMID- 17460305
TI  - Pupil size and retinal straylight in the normal eye.
AB  - PURPOSE: Glare problems originating from bright lights are generally experienced
      more strongly at night. The typical disability glare is known to result from
      retinal straylight. In this study, the effects of pupil diameter and, especially
      in the case of small pupils, of eye wall translucency on the amount of retinal
      straylight were investigated. METHODS: Straylight was measured as a function of
      pupil diameter ranging from 1.3 to >8 mm in five normal subjects by using a white
      light, CRT-based system for scattering angles of 3.5 degrees , 7 degrees , and 14
      degrees . In the study of red-free light, a yellow-LED based system was used with
      the same five subjects for scattering angles of 3.5 degrees , 10 degrees , and 28
      degrees . Data were analyzed to assess effects of (1) inhomogeneity of light
      scattering over the pupil plane, (2) translucency of the eye wall, and (3)
      effects of the periphery of the lens. To estimate the order of magnitude of pupil
      contraction in the typical glare situation, pupil reflexes resulting from the
      sudden appearance of headlight-equivalent bright lights were recorded in three
      subjects in a laboratory environment. RESULTS: For natural pupils (between 2 and
      7 mm diameter), straylight weakly depends on pupil diameter (within 0.2 log
      units). For large scatter angles and small pupil diameters, eye wall translucency
      contributes significantly to straylight in a wavelength- and pigmentation
      dependent manner. Pupil diameters decreased to photopic values under typical
      night-driving glare conditions. CONCLUSIONS: In normal eyes, straylight values
      measured with photopic pupils are by approximation also valid for mesopic and
      scotopic pupils, such as in night driving. Measurement of straylight under large
      angle and small pupil conditions can be used for quantitative assessment of eye
      wall translucency.

PMID- 17460306
TI  - Legibility variations of Chinese characters and implications for visual acuity
      measurement in Chinese reading population.
AB  - PURPOSE: Written Chinese contains an enormous number of characters with a wide
      range of spatial complexities. Consequently, the legibility of Chinese characters
      is expected to vary significantly, and this variability offers the challenge of
      deriving a simple visual function measurement for the Chinese reading population.
      The purpose of this study was to suggest a solution to the challenge through
      psychophysical studies of Chinese character legibility. METHODS: To illustrate
      legibility variations in Chinese characters, visual acuities for six groups of
      Chinese characters from low to high spatial complexities and one group of Sloan
      letters were determined in six normal-sighted Chinese observers. The relationship
      between legibility and optical defocus were then determined for the Landolt C,
      the Snellen E, and three groups of Chinese characters representing low, medium,
      and high spatial complexities in 26 normal-sighted Chinese readers. RESULTS: The
      acuity size of Chinese characters increased steadily with stimulus complexity,
      though at a slower rate than would be expected if visual acuity were based on the
      finest details of the stimuli. The acuity size versus optical defocus functions
      of three Chinese character groups and the Snellen E had similar slopes and
      differed only by a vertical shift, depending on the optotype spatial complexity.
      The function of the Landolt C was significantly steeper. CONCLUSIONS: The
      findings indicate that visual acuity assessment in Chinese readers is complicated
      by the spatial complexity of Chinese characters, but the fact that the Snellen E,
      which is the current national standard of acuity measurement in China, and
      Chinese characters showed similar dependence on optical defocus may indicate a
      potentially valid way to infer functional vision in Chinese readers with Snellen
      E acuity.

PMID- 17460307
TI  - Critical care professionalism in the age of pay-for-performance: from ICUs to
      outpatient critical care clinics.

PMID- 17460308
TI  - Critical care nurses in industry: deserters or leaders?

PMID- 17460309
TI  - Exclusion of patients limits findings in pulse oximeter study.

PMID- 17460310
TI  - Beware of transfusion-related confounders in studies on packed red blood cells.

PMID- 17460312
TI  - Pneumonia observational incidence and treatment: a multidisciplinary process
      improvement study.
AB  - BACKGROUND: Little information is available on the types, causes, and treatment
      of pneumonia in intensive care unit patients in usual clinical practice.
      OBJECTIVE: To characterize treatment of patients with presumed pneumonia in a
      tertiary care intensive care unit and to identify potential areas for improvement
      in care. METHODS: In a prospective, cohort study, the sample consisted of all
      consecutive patients treated in an intensive care unit during a 3-month period.
      For patients with presumed pneumonia, data were collected on incidence of
      pneumonia, diagnostic investigations, microbial isolates, and antibiotics
      prescribed. RESULTS: Of 194 admissions, 73 patients were treated for pneumonia:
      47 had community-acquired pneumonia; 12 had hospital-acquired pneumonia; 12 had
      ventilator-associated pneumonia, both early (7) and late (5); and 2 had intensive
      care unit-acquired pneumonia. Approximately 71% of patients had microbiological
      tests performed. Among 54 microbial isolates, 51.9% were gram-positive bacteria,
      31.5% were gram-negative bacteria, and 9.3% were Candida species. The most
      commonly used antimicrobials were quinolones (54 of 192 prescriptions) and
      cephalosporins (33); each patient received a median of 3 antibiotics.
      CONCLUSIONS: Most cases of pneumonia were community acquired. The most common
      causative organisms were gram-positive cocci. Four quality improvement strategies
      were rationalization of antibiotic use during rounds, nurses' reporting of
      culture results, review of antibiotic appropriateness by a pharmacist, and
      redesign of the clinical information system.

PMID- 17460313
TI  - Prevalence and consequences of nonadherence to hemodialysis regimens.
AB  - Adherence to fluid restrictions and dietary and medication guidelines as well as
      attendance at prescribed hemodialysis sessions of a hemodialysis regimen are
      essential for adequate management of end-stage renal disease. A literature review
      was conducted to determine the prevalence and consequences of nonadherence to the
      different aspects of a hemodialysis regimen and the methodological obstacles in
      research on nonadherence. Nonadherence to the prescribed regimen is a common
      problem in hemodialysis and is associated with increased morbidity and mortality.
      Research on nonadherence is associated with 2 major obstacles: inconsistencies in
      definitions and invalid measurement methods. Further research is needed to
      validate measurement methods and to establish clinically relevant operational
      definitions of nonadherence.

PMID- 17460315
TI  - Improving survival after in-hospital cardiac arrest: the Australian experience.
AB  - BACKGROUND: Survival rates after in-hospital cardiac arrest have not improved
      markedly despite improvements in technology and resuscitation training.
      OBJECTIVES: To investigate clinical variables that influence return of
      spontaneous circulation and survival to discharge after in-hospital cardiac
      arrest. METHODS: An Utstein-style resuscitation template was implemented in a 750
      bed hospital. Data on 158 events were collected from January 2004 through
      November 2004. Significant variables were analyzed by using a multiple logistic
      regression model. RESULTS: Of the 158 events, 128 were confirmed cardiac arrests.
      Return of spontaneous circulation occurred in 69 cases (54%), and the patient
      survived to discharge in 41 (32%). An initial shockable rhythm was present in 42
      cases (33%), with a return of spontaneous circulation in 32 (76%) and survival to
      discharge in 24 (57%). An initial nonshockable rhythm was present in the
      remaining 86 cases (67%), with a return of spontaneous circulation in 37 (43%)
      and survival to discharge in 17 (20%). Witnessed or monitored arrests (P=.006),
      time to arrival of the cardiac arrest team (P=.002), afternoon shift (P=.02), and
      initial shockable rhythm (P=.005) were independently associated with return of
      spontaneous circulation. Location of patient in a critical care area (P=.002),
      initial shockable rhythm (P<.001), and length of resuscitation (P=.02) were
      independently associated with survival to hospital discharge. CONCLUSIONS: The
      high rate of survival to discharge after cardiac arrest is attributed to
      extensive education and the incorporation of semiautomatic external
      defibrillators into basic life support management.

PMID- 17460316
TI  - Stressors and anxiety in patients undergoing coronary artery bypass surgery.
AB  - BACKGROUND: Patients undergoing coronary artery bypass surgery who have increased
      anxiety levels have poorer outcomes than patients with lower levels, yet few
      studies have identified the concerns associated with this anxiety. OBJECTIVE: To
      describe the concerns of patients undergoing coronary artery bypass surgery and
      to identify concerns that were associated with higher levels of anxiety. METHOD:
      Patients (n = 172) were interviewed to determine their concerns and anxiety
      levels before surgery, before discharge, and 10 days after discharge. Multiple
      regression was used to determine the predictors of anxiety. RESULTS: Although
      individual concerns changed over time, anxiety levels did not change from before
      to after surgery, remaining low to moderate. Being female and having more
      concerns about waiting for the surgery, being in pain/discomfort, and resuming
      lifestyle were predictors of increased anxiety before surgery. Predictors of
      increased anxiety while hospitalized after the surgery included taking anxiolytic
      or antidepressant medications, higher anxiety levels before surgery, concerns
      about personal things being inaccessible, and difficulty sleeping. Patients with
      higher anxiety levels after discharge were older, more anxious before surgery,
      and had concerns about being in pain/discomfort. CONCLUSION: Patients waiting for
      coronary artery bypass surgery should be routinely assessed for anxiety before
      the procedure, and interventions to prevent or reduce anxiety should be provided.
      Interventions must be multifactorial, including information and support for pain
      management and realistic information about surgery schedules and resuming
      lifestyle after the surgery. Women and older patients may need to be targeted for
      intervention.

PMID- 17460318
TI  - Utility of observer-rated and self-report instruments for detecting major
      depression in women after cardiac surgery: a pilot study.
AB  - BACKGROUND: Major depression is common after coronary artery bypass graft surgery
      and is associated with increased mortality and morbidity. Clinicians have few
      practical options for detecting depression, especially in women, who are at
      higher risk for depression than men. OBJECTIVES: To evaluate the clinical utility
      of common self-report and observer-rated instruments for detection of major
      depression in women after coronary artery bypass graft surgery. METHODS: In 66
      women being discharged after coronary artery bypass graft surgery, 4 instruments
      were completed: the Hamilton Depression Rating Scale, Beck Depression Inventory,
      Beck Depression Inventory Short Form, and Beck Depression Inventory for Primary
      Care. For each instrument, receiver-operating-characteristic curves were
      analyzed, and positive and negative predictive values were calculated for cutoff
      points determined from the curves. RESULTS: At hospital discharge, all 4
      instruments yielded highly accurate curves. Compared with cutoffs suggested for
      patients without medical illness and hospitalized nonsurgical patients,
      identified cutoffs for screening were higher when all types of depressive
      symptoms (cognitive, affective, behavioral, somatic) were measured with the
      Hamilton Depression Rating Scale and the Beck Depression Inventory but lower when
      only cognitive and/or affective symptoms were measured with the 2 subscales of
      the Beck Depression Inventory. CONCLUSIONS: The Hamilton Depression Rating Scale
      and both subscales of the Beck Depression Inventory may be useful for detecting
      major depression in women shortly after coronary artery bypass graft surgery.
      Further study is warranted to confirm cutoffs in these patients.

PMID- 17460319
TI  - Attitudes toward and beliefs about family presence: a survey of healthcare
      providers, patients' families, and patients.
AB  - BACKGROUND: Although some healthcare providers remain hesitant, family presence,
      defined as the presence of patients' family members during resuscitation and/or
      invasive procedures, is becoming an accepted practice. Evidence indicates that
      family presence is beneficial to patients and their families. OBJECTIVES: To
      describe and compare the beliefs about and attitudes toward family presence of
      clinicians, patients' families, and patients. METHODS: Clinicians, patients'
      families, and patients in the emergency department and adult and neonatal
      intensive care units of a 300-bed urban academic hospital were surveyed. RESULTS:
      Surveys were completed by 202 clinicians, 72 family members, and 62 patients.
      Clinicians had positive attitudes toward family presence but had concerns about
      safety, the emotional responses of the family members, and performance anxiety.
      Nurses had more favorable attitudes toward family presence than physicians did.
      Patients and their families had positive attitudes toward family presence.
      CONCLUSIONS: Family presence is beneficial to patients, patients' families, and
      healthcare providers. As family presence becomes a more accepted practice,
      healthcare providers will need to accommodate patients' families at the bedside
      and address the barriers that impede the practice.

PMID- 17460321
TI  - AJCC Patient Care Page. Family presence during CPR and invasive procedures.

PMID- 17460322
TI  - Evaluation of a tobacco cessation curricular intervention among acute care nurse
      practitioner faculty members.
AB  - BACKGROUND: In 2002, a report indicated that tobacco-related curricular content
      in educational programs for acute care nurse practitioners was insufficient. To
      provide healthcare professionals with the necessary knowledge and skills to
      intervene with patients who smoke tobacco, the Summer Institute for Tobacco
      Control Practices in Nursing Education was implemented at Georgetown University
      in Washington, DC. OBJECTIVE: To evaluate the impact of a train-the-trainer
      program in which the Rx for Change: Clinician-Assisted Tobacco Cessation
      curriculum was used among faculty members of acute care nurse practitioner
      programs. METHODS: Thirty faculty members participated in the 2-day train-the
      trainer program. Surveys were administered at baseline and 12 months after
      training to examine perceived effectiveness for teaching tobacco content, the
      value of using an evidence-based national guideline, and the number of hours of
      tobacco content integrated in curricula. RESULTS: The percentage of faculty
      members who devoted at least 3 hours to tobacco education increased from 22.2% to
      74.1% (P<.001). Perceived effectiveness in teaching tobacco cessation also
      increased (P < .001), as did mean scores for the perceived value of using an
      evidence-based national guideline (P<.001). CONCLUSIONS: Use of the Rx for Change
      train-the-trainer program can enhance the level of tobacco education provided in
      acute care nurse practitioner programs. Widespread adoption of an evidence-based
      tobacco education in nursing curricula is recommended to help decrease tobacco
      related morbidity and mortality.

PMID- 17460323
TI  - Lessons from the classics: conflict and tragedy in critical care at the end of
      life.

PMID- 17460324
TI  - Iatrogenic sick sinus syndrome.

PMID- 17460325
TI  - Cardiac arrhythmias after traumatic amputation.

PMID- 17460326
TI  - Severe sepsis and acute respiratory distress syndrome from community-acquired
      legionella pneumonia: case report.
AB  - A case of a young man with community-acquired pneumonia, severe acute respiratory
      distress syndrome, and sepsis is reported. Treatment with antibiotics and various
      modes of mechanical ventilation in the intensive care unit were unsuccessful. A
      urinary legionella antigen test was positive for Legionella pneumophila.

PMID- 17460327
TI  - Thematic review series: adipocyte biology. Sympathetic and sensory innervation of
      white adipose tissue.
AB  - During our study of the reversal of seasonal obesity in Siberian hamsters, we
      found an interaction between receptors for the pineal hormone melatonin and the
      sympathetic nervous system (SNS) outflow from brain to white adipose tissue
      (WAT). This ultimately led us and others to conclude that the SNS innervation of
      WAT is the primary initiator of lipid mobilization in these as well as other
      animals, including humans. There is strong neurochemical (norepinephrine
      turnover), neuroanatomical (viral tract tracing), and functional (sympathetic
      denervation-induced blockade of lipolysis) evidence for the role of the SNS in
      lipid mobilization. Recent findings suggest the presence of WAT sensory
      innervation based on strong neuroanatomical (viral tract tracing,
      immunohistochemical markers of sensory nerves) and suggestive functional
      (capsaicin sensory denervation-induced WAT growth) evidence, the latter implying
      a role in conveying adiposity information to the brain. By contrast,
      parasympathetic nervous system innervation of WAT is characterized by largely
      negative neuroanatomical evidence (viral tract tracing, immunohistochemical and
      biochemical markers of parasympathetic nerves). Functional evidence (intraneural
      stimulation and in situ microdialysis) for the role of the SNS innervation in
      lipid mobilization in human WAT is convincing, with some controversy regarding
      the level of sympathetic nerve activity in human obesity.

PMID- 17460328
TI  - Apolipoprotein A-V association with intracellular lipid droplets.
AB  - Apolipoprotein A-V (apoA-V) plays a key role in the regulation of triglyceride
      (TG) metabolism. Given the very low concentration of apoA-V in plasma, we
      hypothesized that apoA-V may influence plasma TG levels by affecting the assembly
      and/or secretion of apoB-containing lipoproteins. When apoA-V was overexpressed
      in cultured Hep3B cells, neither the amount of apoB secreted nor the density
      distribution of apoB-containing lipoproteins was affected. Fluorescence
      microscopy and cell lysate immunoprecipitation studies revealed that apoA-V is
      not associated with apoB intracellularly, yet immunoprecipitation of apoA-V from
      the cell culture medium resulted in coprecipitation of apoB. These data suggest
      that the apoA-V association with apoB-containing lipoproteins is a postsecretory
      event. Confocal fluorescence microscopy revealed the presence of apoA-V in
      distinct cellular structures. Based on Nile Red staining, we identified these
      structures to be intracellular lipid droplets. These data suggest that apoA-V has
      a unique association with cellular lipids and, therefore, may be involved in the
      storage or mobilization of intracellular lipids.

PMID- 17460329
TI  - Thermic and glycemic responses to bread and pasta meals with and without prior
      low-intensity exercise.
AB  - The purpose of the study was to investigate thermic and glycemic responses to
      conventional meals with and without prior low-intensity exercise. Fourteen
      healthy volunteers (7 men, 7 women) undertook 4 treatments, 2 bread and 2 pasta
      meals, either with (E) or without (NE) prior exercise (a 45-min treadmill walk).
      Meals provided 58 g carbohydrate and 2360 kJ. Energy expenditure and blood
      glucose concentrations were measured before and for 3 h after the meals. The
      thermic effect of food (TEF) was lower after pasta (121 +/- 32 kJ/3 h) than after
      bread (154 +/- 62 kJ/3 h), P=0.009, but was not affected by exercise. Glycemic
      responses were lower after E (155 +/- 113 mmol x L(-1) x 3 h(-1)) than NE (199 +/
      97 mmol x L(-1) x 3 h(-1)) after pasta (P=0.020) but not after bread. TEF was
      lower after pasta than bread but was not affected by prior low-intensity
      exercise. The effects of exercise on glycemic responses to meals were
      inconsistent.

PMID- 17460330
TI  - The hydration profile of female cricket players during competition.
AB  - This study investigated the hydration profile of high-performance female cricket
      players competing at a national tournament. The profile comprised hydration
      monitoring (n=18) and a questionnaire (n=20). Our objectives were to 1) advance
      the understanding of fluid losses in cricket sessions across a tournament and 2)
      assess the hydration knowledge and practices in female cricket players. Body mass
      before and after each game inning was recorded in order to estimate sweat rate,
      sweat loss, and percentage body-mass loss. Comparisons were made between groups
      categorized according to level of activity during each inning. When sweat rates
      were estimated according to actual activity time, results were in the range of
      those in other female team sports but less than results from male cricket
      players. A range of knowledge of hydration issues was also observed. This study
      supports the need for individualized hydration recommendations and provides
      direction for further hydration education in women's cricket.

PMID- 17460331
TI  - The effects of caffeine in women during aerobic-dance bench stepping.
AB  - People of all ages and fitness levels participate regularly in aerobic-dance
      bench stepping (ADBS) to increase fitness and control body weight. Any reasonable
      method for enhancing the experience or effectiveness of ADBS would be beneficial.
      This study examined the acute effects of a single dose of caffeine on
      physiological responses during ADBS in women. When compared with a placebo,
      neither a 3- nor a 6-mg/kg dose of caffeine altered physiological responses or
      rating of perceived exertion (RPE) in 20 women (age 19-28 y) of average fitness
      level, not habituated to caffeine, while they performed an ADBS routine. Since
      neither dose of caffeine had any effect on VO2, VCO2, minute ventilation,
      respiratory-exchange ratio, rate of energy expenditure, heart rate, or RPE during
      ADBS exercise, it would not be prudent for a group exercise leader to recommend
      caffeine to increase energy cost or decrease perception of effort in an ADBS
      session. Furthermore, caffeine ingestion should not interfere with monitoring
      intensity using heart rate or RPE during ADBS.

PMID- 17460332
TI  - Caffeinated sports drink: ergogenic effects and possible mechanisms.
AB  - This double-blind experiment examined the effects of a caffeinated sports drink
      during prolonged cycling in a warm environment. Sixteen highly trained cyclists
      completed 3 trials: placebo, carbohydrate-electrolyte sports drink (CES), and
      caffeinated sports drink (CES+CAF). Subjects cycled for 135 min, alternating
      between 60% and 75% VO2max every 15 min for the first 120 min, followed by a 15
      min performance ride. Maximal voluntary (MVC) and electrically evoked contractile
      properties of the knee extensors were measured before and after cycling. Work
      completed during the performance ride was 15-23% greater for CES+CAF than for the
      other beverages. Ratings of perceived exertion were lower with CES+CAF than with
      placebo and CES. After cycling, the MVC strength loss was two-thirds less for
      CES+CAF than for the other beverages (5% vs. 15%). Data from the interpolated
      twitch technique indicated that attenuated strength loss with CES+CAF was
      explained by reduced intrinsic muscle fatigue.

PMID- 17460334
TI  - Creatine and glycerol hyperhydration in trained subjects before exercise in the
      heat.
AB  - The authors examined the effects of combined creatine (Cr) and glycerol (Gly)
      supplementation on responses to exercise in the heat. Subjects (N=24) were
      matched for body mass and assigned to either a Cr or placebo (Pl) group. Twice
      daily during two 7-d supplementation regimens, the Cr group received 11.4 g of Cr
      x H2O and the Pl group received 11.4 g of glucose. Subjects in both groups also
      ingested 1 g of Gly/kg body mass (twice daily) in either the first or the second
      supplementation regimen. This design allowed 4 possible combinations of
      supplements to be examined (Pl/Pl, Pl/Gly, Cr/Pl, and Cr/Gly). Exercise trials
      were conducted pre- and postsupplementation at 30 degrees C and 70% relative
      humidity. In the Pl group, total body water (TBW) increased by 0.50 +/- 0.28 L
      after Gly and in the Cr group by 0.63 +/- 0.33 L after Pl and by 0.87 +/- 0.21 L
      after Gly. Both Cr/Pl and Cr/Gly resulted in significantly attenuated heart rate,
      rectal temperature, and perceived effort during exercise, although no regimen had
      any effect on performance. The addition of Gly to Cr significantly increased TBW
      more than Cr alone (P=0.02) but did not further enhance the attenuation in HR,
      Tre, and RPE during exercise. These data suggest that combined Cr and Gly is an
      effective method of hyperhydration capable of reducing thermal and cardiovascular
      responses.

PMID- 17460335
TI  - Eight weeks of aromatase inhibition using the nutritional supplement Novedex XT:
      effects in young, eugonadal men.
AB  - This study examined the effects of an aromatase-inhibiting nutritional supplement
      on serum steroid hormones, body composition, and clinical safety markers. Sixteen
      eugonadal young men ingested either Novedex XT or a placebo daily for 8 wk,
      followed by a 3-wk washout period. Body composition was assessed and blood and
      urine samples obtained at weeks 0, 4, 8, and 11. Data were analyzed by 2-way
      repeated-measures ANOVA. Novedex XT resulted in average increases of 283%, 625%,
      566%, and 438% for total testosterone (P=0.001), free testosterone (P=0.001),
      dihydrotestosterone (P=0.001), and the testosterone:estrogen ratio (P=0.001),
      respectively, whereas fat mass decreased 3.5% (P=0.026) during supplementation.
      No significant differences were observed in blood and urinary clinical safety
      markers or for any of the other serum hormones (P>0.05). This study indicates
      that Novedex XT significantly increases serum androgen levels and decreases fat
      mass.

PMID- 17460337
TI  - [Regulation of the use of hospital-restricted drugs].

PMID- 17460336
TI  - Postexercise carbohydrate-protein- antioxidant ingestion decreases plasma
      creatine kinase and muscle soreness.
AB  - The authors investigated the effects of postexercise carbohydrate-protein
      antioxidant (CHO+P+A) ingestion on plasma creatine kinase (CK), muscle soreness,
      and subsequent cross-country race performance. Twenty-three runners consumed 10
      mL/kg body weight of CHO or CHO+P+A beverage immediately after each training
      session for 6 d before a cross-country race. After a 21-d washout period,
      subjects repeated the protocol with the alternate beverage. Postintervention CK
      (223.21 +/- 160.71 U/L; 307.3 +/- 312.9 U/L) and soreness (medians = 1.0, 2.0)
      were significantly lower after CHO+P+A intervention than after CHO, despite no
      differences in baseline measures. There were no overall differences in running
      performance after CHO and CHO+P+A interventions. There were, however, significant
      correlations between treatment differences and running mileage, with higher
      mileage runners having trends toward improved attenuations in CK and race
      performance after CHO+P+A intervention than lower mileage runners. We conclude
      that muscle damage incurred during training was attenuated with postexercise
      CHO+P+A ingestion, which could lead to performance improvements in high-mileage
      runners.

PMID- 17460338
TI  - [Renal cancer and arctic wisdom].

PMID- 17460339
TI  - [Mastoiditis in children in Iceland].
AB  - INTRODUCTION: Mastoiditis is an infection in the mastoid process and is a
      complication of otitis media. Studies have revealed that the incidence might be
      increasing with altered antibiotic usage. The aim of the current study was to
      describe the epidemiology, clinical symptoms and treatment of mastoiditis in
      Iceland during the last two decades with special emphasis on children and to
      study possible correlations between antibiotic use and incidence of mastoiditis.
      PATIENTS AND METHODS: Information on patients diagnosed with mastoiditis during
      the period 1984-2002 at The Children's Hospital Iceland, The Department of
      Paediatrics, Landakoti and Landspitali--University Hospital Iceland was gathered
      and clinical data were recorded from patients records of children diagnosed with
      mastoiditis during 1999-2002. Information on antibiotic use during the years 1989
      2002 was obtained from the Ministry of Health in Iceland. RESULTS: Eighty-four
      patients were diagnosed with mastoiditis during the period 1984-2002. Of those,
      52 (62%) were children less than 18 years of age. The mean age of those children
      was 2 years and 8 months. Boys were 58%. Twenty six (50%) of the children were
      less than three years old. During the years 1999-2002, a total of 28 children
      were diagnosed; the mean age was 2 years and 2 months. Fifteen children (54%)
      sought medical attention within a week prior to admission to hospital and had
      been diagnosed with otitis media. Eleven children (73%) were appropriately
      treated with antibiotics prior to the diagnosis of mastoiditis but four (27%)
      received no antibiotics. During the period 1989-2002, a statistically significant
      correlation was detected between decreased antibiotic use among children and
      increasing incidence of mastoiditis (r=-0.68; p=0.007). DISCUSSION: Following
      changes in guidelines for antibiotic prescriptions for otitis media in Iceland
      during the nineties, antibiotic use in children decreased at the same time as the
      incidence for mastoiditis increased. It is uncertain, however, if a causal
      relationship exists. It is important to diagnose and appropriately treat otitis
      media, while staying alert for serious complications, especially in young
      children.

PMID- 17460340
TI  - [Renal cell carcinoma in Iceland].
AB  - Renal Cell Carcinoma (RCC) is by far the most common malignant tumor of the
      kidney. It is a disease with many faces, known for its clinical diversity and
      often unpredictable behavior. Less is known about its etiology and risk factors
      than for most other human cancers. Mortality-to-incidence ratio is higher
      compared to other urologic malignancies, and the malignancy confers adverse
      prognosis for the majority of patients. At the same time as incidence of RCC has
      been rising globally, progress has been made in the understanding of the disease,
      especially within the field of genetics and biological research. Immunotherapies
      together with tyrosine kinase inhibitors and growth factor/angiogenesis
      modulators are being developed for patients with advanced disease and
      improvements have been made in the surgical approach. This, together with
      increased incidental detection secondary to the widespread use of modern imaging
      procedures, suggests improved prognosis of these patients in the future. For
      unknown reasons the incidence of RCC is higher in Iceland than in most other
      countries, about 30 new cases being diagnosed every year, with 14 deaths due to
      RCC occurring. This evidence-based article reviews major studies on different
      aspects of RCC with special emphasis on the epidemiology and clinicopathological
      presentation of the disease in Iceland.

PMID- 17460341
TI  - [New drug treatment for age-related macular degeneration].
AB  - New drugs for age-related macular degeneration present a major advance in the
      treatment of the most common cause of blindness in Iceland. Vascular endothelial
      growth factor antibodies reduce the risk of blindness and improve vision in
      patients with age-related macular degeneration.

PMID- 17460342
TI  - Burnout, vicarious traumatization and its prevention.
AB  - Previous studies on burnout and vicarious traumatization are reviewed and
      summarized with a list of signs and symptoms. From the author's own observations
      two histories of caregivers working with torture survivors are described which
      exemplify the risk,implications and consequences of secondary trauma.
      Contributing factors in the social and political framework in which caregivers
      operate are analyzed and possible means of prevention suggested, particularly
      focussing on the conflict of roles when providing evaluations on trauma victims
      for health and immigration authorities. Caregivers working with victims of
      violence carry a high risk of suffering from burnout and vicarious traumatization
      unless preventive factors are considered such as: self care, solid professional
      training in psychotherapy, therapeutic self-awareness, regular self-examination
      by collegial and external supervision, limiting caseload, continuing professional
      education and learning about new concepts in trauma, occasional research
      sabbaticals, keeping a balance between empathy and a proper professional distance
      to clients, protecting oneself against being mislead by clients with fictitious
      PTSD. An institutional setting should be provided in which the roles of
      therapists and evaluators are separated. Important factors for burnout and
      vicarious traumatization are the lack of social recognition for caregivers and
      the financial and legal outsider status of many centers. Therefore politicians
      and social insurance carriers should be urged to integrate facilities for
      traumatized refugees into the general health care system and centers should work
      on more alliances with the medical mainstream and academic medicine.

PMID- 17460343
TI  - PTSD symptom changes in refugees.
AB  - Extreme traumatic events such as a threatened death or serious injury are common
      experiences for refugees, many of whom display levels of Post-traumatic Stress
      Disorder (PTSD). Our preliminary investigation of 19 refugees examined whether
      acceptance of an individual application for Convention Refugee status is a factor
      in recovery from PTSD. Based on the traumatic experiences identified with the
      Harvard Trauma Questionnaire, differential rates of recovery from PTSD and
      generalized distress were prospectively compared in refugees who had either
      received acceptance in their application for refugee status (n=10) or had been
      denied status (n=9). PTSD was diagnosed according to criteria outlined in the DSM
      IV and distress was measured with the Brief Symptom Inventory. Unique to this
      study was the assessment of the refugee Claimant prior to his or her individual
      appearance before the Immigration and Refugee Board in Canada. The data support
      the hypothesis that a positive outcome for the hearing would significantly relate
      to a reduced DSM-IV PTSD symptom count and to a reduced generalized distress.
      Participants who received a positive hearing outcome showed significant recovery
      relative to those who were denied refugee status. Notwithstanding the small paper
      size, the results are discussed in terms of how the promise of future freedom
      from persecution combines with making actual disclosures before the Immigration
      and Refugee Board to start the process of rehabilitation.

PMID- 17460344
TI  - Self-harming behaviour and dissociation in complex PTSD.

PMID- 17460345
TI  - Domestic violence against women--an international concern.
AB  - Domestic violence is a pattern of assault and coercive behaviour including
      physical, sexual and psychological attacks, by a person against his/her own
      intimate partner. Women are more frequently the victims. After a global overview
      of the prevalence and nature of domestic violence against women especially in
      Mauritius, this articles provides a discussion about health problems and risk
      factors among the female victims with the objective of giving preventive measures
      to eradicate it from society. NGOs, along with legislative measures, have proven
      helpful in improving quality of life and preventing violence-related injuries
      among women. The health sector also plays an important role as part of multi
      sector efforts in early detection and prevention of cases of domestic violence.
      Psychiatrists are in a unique position for early identification of such patients
      as well as intervention.

PMID- 17460346
TI  - The physical and psychological effects of torture in Kurds seeking asylum in the
      United Kingdom.
AB  - There were over 2000 applications for asylum from Turkish nationals to the UK in
      2003. A large proportion of these were person of Kurdish origin, many of whom
      claimed to have suffered torture. We sought to evaluate the physical and
      psychological effects of torture in those with physical injuries. A total of 97
      Kurdish asylum seekers requiring medical evaluation for evidence of torture were
      examined and interviewed in the presence of an interpreter. Physical injuries,
      pain, disability and psychopathology were documented for each. A wide variety of
      injuries and psychological disorders were documented. Posttraumatic stress
      disorder, major depression and organic brain damage were present in a substantial
      proportion of those surveyed. Methods of torture not previously documented were
      revealed. There are long term healthcare needs of this population, which are
      complex and require a multidisciplinary approach. Survivors of torture may be
      disadvantaged in the asylum process because of organic brain damage or major
      psychological disturbance.

PMID- 17460347
TI  - Medical physical examination in connection with torture.

PMID- 17460348
TI  - The medical aspects of the UN Convention against Torture.

PMID- 17460349
TI  - Views on the US ''interrogation'' behaviour.

PMID- 17460350
TI  - Heavy ion microbeam irradiation induces ultrastructural changes in isolated
      single fibers of skeletal muscle.
AB  - The effects of heavy ion microbeams on muscle fibers isolated from mouse skeletal
      muscles were examined by electron microscopy. The plasma membranes of heavy ion
      beam-irradiated areas of muscle fibers showed irregular protrusions and
      invaginations. In the cytoplasm, an irregular distribution of microfilaments was
      found near the plasma membrane. Sarcoplasmic reticula in the irradiated regions
      showed a distended appearance with flocculent material within the lumen. These
      changes were seen as early as 2 min after irradiation, and persisted until as
      late as 22 min after irradiation. Many autophagic vacuoles could be seen at 7 min
      after irradiation. At 22 min, the vacuoles became more prominent and showed more
      variety. These observations suggest that heavy ion beam irradiation causes
      disruption of the cellular architecture and the autophagy is involved in removal
      of this disruption.

PMID- 17460351
TI  - The new function of two ubiquitin C-terminal hydrolase isozymes as reciprocal
      modulators of germ cell apoptosis.
AB  - Ubiquitination is required throughout all developmental stages of mammalian
      spermatogenesis. The two ubiquitin C-terminal hydrolase (UCH) enzymes, UCH-L1 and
      UCH-L3, deubiquitinate ubiquitin-protein conjugates and control the cellular
      balance of ubiquitin. These two UCH isozymes have 52% amino acid identity and
      share significant structural similarity. A new function of these two closely
      related UCH enzymes during spermatogenesis which is associated with germ cell
      apoptosis has been analyzed. Apoptosis, in general, is thought to be partly
      regulated by the ubiquitin-proteasome system. During spermatogenesis, apoptosis
      controls germ cell numbers and eliminates defective germ cells to facilitate
      testicular homeostasis. In this paper, I review the distinct function of the two
      UCH isozymes in the testis of gad and Uchl3 knockout mice, which are strongly but
      reciprocally expressed during spermatogenesis. In addition, the importance of
      UCHL1-dependent apoptosis for normal spermatogenesis and sperm quality control is
      discussed.

PMID- 17460352
TI  - Pharmacokinetic interactions of flunixin meglumine and enrofloxacin in ICR mice.
AB  - We examined the pharmacokinetic interactions of enrofloxacin and flunixin in male
      ICR mice that were subcutaneously (SC) administered with both or either one of
      the drugs. The experiments were performed on the following three groups: flunixin
      alone (2 mg/kg, SC), combination of flunixin (2 mg/kg, SC) and enrofloxacin (10
      mg/kg, SC), and enrofloxacin alone (10 mg/kg, SC). Blood samples were collected
      at 5, 15 and 30 min, and 1, 2, 3, 4, 5 and 6 h after the drug administration, and
      the pharmacokinetic parameters of flunixin and enrofloxacin were evaluated from
      the plasma drug concentrations. Significant changes were detected in the
      pharmacokinetics of flunixin following its coadministration with enrofloxacin.
      Coadministration of flunixin and enrofloxacin resulted in a 41% increase of the
      area under the curve (AUC) and a 53% extension of the terminal half-life of
      flunixin; moreover, flunixin attained the maximum plasma drug concentration 2.75
      times faster than when administered alone. The terminal rate constant and the
      maximum plasma drug concentration showed significant decreases of 34% and 33%,
      respectively, following the coadministration of enrofloxacin and flunixin as
      compared to those following the administration of flunixin alone. In contrast, no
      significant difference in the pharmacokinetics of enrofloxacin was detected
      following its coadministration with flunixin, as compared to those following the
      administration of enrofloxacin alone. Following the administration of
      enrofloxacin alone or its coadministration with flunixin, the plasma level of
      ciprofloxacin, the metabolite of enrofloxacin, was very low or undetectable. In
      conclusion, the pharmacokinetics of flunixin in ICR mice are altered by the
      coadministration of flunixin and enrofloxacin.

PMID- 17460353
TI  - Upregulation of galectin-3 by Corynebacterium kutscheri infection in the rat
      lung.
AB  - Corynebacterium (C) kutscheri and Staphylococcus aureus were isolated from two
      Sprague-Dawley (SD) rats with a hemisected spinal cord. Grossly, gray-white
      bulging foci and abscesses were distributed throughout the parenchyma of the
      lung. Pathologically, severe necrotizing lobar pneumonia with abscesses and
      fibrinous pleuritis were observed. Immunohistochemical analysis found
      accumulation of galectin-3 in alveolar macrophages and the alveolar interstitial
      region. No other viral or bacterial pathogens were detected in these animals. In
      addition, similar pathogenic changes and accumulation of galectin-3 were observed
      in the lungs of SD rats experimentally infected with C. kutscheri. Using northern
      blot analysis, the relative galectin-3 and GAPDH mRNA levels were 4.6 to 9.3
      times higher in C. kutscheri-infected lung than in uninfected controls. These
      results demonstrate that a single C. kutscheri infection can induce the
      upregulation of galectin-3 in the lung and that this molecule may have an
      important pathogenic role in C. kutscheri infections in rats.

PMID- 17460354
TI  - Functional polymorphisms of the Lss and Fdft1 genes in laboratory rats.
AB  - We previously identified mutant alleles of the lanosterol synthase (Lss) and
      farnesyl diphosphate farnesyl transferase 1 (Fdft1) genes, which function in the
      cholesterol biosynthesis pathway, as determinants for hereditary cataracts in the
      SCR rat strain. Lss(S) and Fdft1(S) were established as hypomorphic alleles with
      missense nucleotide substitutions, while Lss(l) is a null allele with nucleotide
      deletion/insertion mutations. Here we report a more detailed characterization of
      the rat Lss and Fdft1 genes. Screening of various laboratory rat strains revealed
      that the hypomorphic Lss(S) and Fdft1(S) alleles are not specific to the SCR
      strain, but are widely prevalent in other laboratory rat strains. Meanwhile,
      Lss(l) was not found in any rat strains examined. It was also found that
      functional inter-strain polymorphisms are present in the Lss upstream regulatory
      region. The BN strain had a higher potential for expression of Lss transcripts
      than ACI and SCR under conditions where cholesterol synthesis is necessary. SCR
      was less efficient than BN and ACI in suppressing Lss transcription in
      circumstances when cholesterol synthesis should be halted. These findings not
      only imply that there is a genetic polymorphism for cholesterol homeostasis in
      laboratory rats, but also point to the possibility that rat strains with
      different Lss alleles exhibit different responses to measures intervening in
      cholesterol metabolism.

PMID- 17460355
TI  - Additive effect of vitamin K2 and risedronate on long bone mass in
      hypophysectomized young rats.
AB  - Hypophysectomy (HX) arrests bone growth and induces osteopenia in the long bones
      of rats. The present study investigated the combined effect of vitamin K(2) and
      risedronate on long bone mass in HX rats, in order to determine whether treatment
      with these two agents had an additive effect. Forty female Sprague-Dawley rats
      were hypophysectomized at 6 weeks of age by the supplier, and were shipped to our
      laboratory at three days after surgery along with ten intact rats that served as
      age-matched controls. The study was started on the day when the rats were
      received. Three HX rats were excluded from the study because of the failure of
      HX. Forty-seven rats (6 weeks old) were assigned to the following 5 groups by the
      stratified weight randomization method: intact controls, HX alone, HX + vitamin
      K(2) (30 mg/kg, p.o., daily), HX + risedronate (2.5 microg/kg, s.c., 5 days a
      week), and HX + vitamin K(2) + risedronate. The dosing period was 4 weeks. HX
      resulted in a decrease of the femoral bone area, bone mineral content (BMC) and
      bone mineral density (BMD), as well as a decrease in the cancellous bone mass of
      the proximal tibial metaphysis and the total tissue and cortical areas of the
      tibial diaphysis. These changes were associated with a marked reduction in the
      serum level of insulin like growth factor (IGF)-I and with elevation of serum
      alkaline phosphatase (ALP) and pyridinoline. Administration of vitamin K(2)
      increased the serum ALP level in HX rats, but did not affect any of the other
      parameters. On the other hand, risedronate ameliorated the decrease of femoral
      BMD and cancellous bone mass at the proximal tibial metaphysis in HX rats without
      affecting the serum IGF-I level, as a result of not causing a significant
      elevation of serum pyridinoline. Vitamin K(2) and risedronate combined had an
      additive effect on the femoral bone area, BMC and BMD, and the combined treatment
      group did not show any significant reduction of the total tissue and cortical
      areas at the tibial diaphysis, as well as a reduced serum pyridinoline level
      compared with untreated rats and an increased serum ALP level compared with
      untreated or risedronate-treated rats. These results suggest that risedronate had
      a positive effect on the BMD and cancellous bone mass of long bones in HX rats.
      Despite the lack of a significant effect of vitamin K(2) on bone mass parameters,
      it had an additive effect with risedronate on the BMC, BMD and cortical bone mass
      of long bones in HX rats.

PMID- 17460356
TI  - Establishment of a rabbit model of superior vena cava obstruction.
AB  - OBJECTIVE: To explore a method of establishing a rabbit model of superior vena
      cava obstruction (SVCO) by injecting VX2 tumor cell suspension transcutaneously
      under ultrasound guidance. METHODS: A suspension of VX2 tumor cells was prepared
      under sterile conditions. Fifteen adult healthy New Zealand White rabbits were
      enrolled in the experiment. Under ultrasound guidance, about 0.1 ml of the living
      tumor cell suspension was transcutaneously injected in front of the anterior wall
      of the right superior vena cava (SVC). The lumen, wall, blood flow of SVCs and
      adjacent tissues were examined with gray-scale and color Doppler ultrasonography,
      every 3 days starting from the 9th day after injection. Meanwhile, CT scanning
      and digital subtraction angiography (DSA) were also performed. The rabbits were
      dissected immediately after death and tissue samples were collected for
      pathologic examination. RESULTS: Fourteen out of 15 rabbits developed tumors that
      were located close to SVCs and/or SVCs cavity, which was shown by
      ultrasonography. The diameters of the tumors were 80.7 +/- 4.3 mm. These tumors
      grew close to SVCs area and resulted in compression and infiltration of SVCs. CT
      scanning and DSA confirmed the establishment of the SVCO model. The achievement
      rate of the SVCO model was 93.3%. No rabbit died of complications. CONCLUSION: A
      method of establishing a rabbit SVCO model by injecting VX2 tumor cell suspension
      under ultrasonographic guidance was established successfully, and it proved to be
      simple, effective and repeatable. The imaging characteristics of this model are
      in good accordance with those of SVCO in patients.

PMID- 17460357
TI  - The pharmacokinetic properties of methamphetamine in rats with previous repeated
      exposure to methamphetamine: the differences between Long-Evans and Wistar rats.
AB  - Repeated treatment with methamphetamine (METH) causes long-term behavioral
      changes, so-called behavioral sensitization (BS), in humans as well as
      experimental animals. However, there are no reports as to whether repeated METH
      treatment can establish BS in stress-sensitive Long-Evans (LE) rats. Thus, we
      investigated the effect of repeated METH treatment (5 mg/kg x 5 days) on the
      establishment of BS in LE rats. Wistar (WIS) rats were used as a reference. In LE
      rats, repeated METH treatment failed to cause BS although it did enhance METH
      induced hyperlocomotion in WIS rats. The levels of METH in brain dialysate and
      the ratio of the area under the concentration-time curve area in plasma to that
      in brain dialysate was increased in repeated METH-treated WIS rats as reported
      previously, but not in repeated METH-treated LE rats. METH increases plasma
      corticosterone (CORT) in both strains. However, the intensity of increment of
      CORT by repeated METH was lower in LE rats than that in WIS rats. Repeated METH
      treatment decreased the expression of METH-transposable and CORT-sensitive
      transporter, organic cation transporter 3 (OCT3), in the brain of WIS rats.
      However, the intensity of the decrement of OCT3 with repeated METH treatment was
      similar between both strains. Taken together, these results suggest that the lack
      of establishment of BS in LE rats might have been caused by the unchanged brain
      penetration of METH after repeated METH administration, and that the differential
      CORT response to METH is an important strain difference.

PMID- 17460358
TI  - NARCOBIT: a newly developed inhalational anesthesia system for mice.
AB  - NARCOBIT is the first anesthetic system for mice and rats to incorporate a
      ventilator. Therefore, it is expected to improve the reliability of mice and rat
      experiments by accurately controlling and maintaining the depth of anesthesia. In
      this study, we used NARCOBIT for inducing inhalational anesthesia in mice and
      evaluated the changes in their hemodynamic parameters. ICR mice were anesthetized
      with 5% isoflurane and room air, followed by endotracheal intubation.
      Subsequently, they were mechanically ventilated, and anesthesia was maintained by
      2% isoflurane for a 60-min period (maintenance state) using NARCOBIT. In study 1,
      the heart rate (HR) and mean arterial blood pressure (MAP) were measured. The
      skin blood flow (SBF) from the hind legs was continuously measured during the
      maintenance state. Subsequently, the concentration-dependent effects of
      isoflurane on MAP were examined. In study 2, blood samples were obtained from the
      abdominal aorta for blood gas analysis. The HR and MAP decreased after anesthesia
      but were stable during the maintenance state. Decreased MAP and concentration
      dependent effects of isoflurane were observed. The SBF increased slightly during
      the maintenance state but this increase was insignificant. The blood gas analysis
      showed neither hypoxia nor hypercapnia. Since the use of NARCOBIT enables the
      anesthetic concentration of isoflurane to be easily changed, a suitable
      anesthesia depth can be obtained for experimental purposes. Therefore, we
      conclude that NARCOBIT can be used for providing inhalational anesthesia to mice.

PMID- 17460359
TI  - Changes of estrous cycles with aging in female F344/n rats.
AB  - Changes of estrous cycles with aging of F344/N rats between 1 and 30 months of
      age (M) were monitored by vaginal smear cytology. The vaginal opening and first
      cornified cell phase were identified at 1.3 +/- 0.1 M and 1.5 +/- 0.2 M,
      respectively. Thereafter, estrous cycles showed about 5-day intervals, and ceased
      at 16.4 +/- 1.2 M. Thereafter irregular appearance of single cornified cell
      phases without the preceding of nucleated cell phases interspersed with a
      predominant leukocyte phase was seen in vaginal smears until 26.9 +/- 0.5 M.
      Growing and mature follicles as well as corpora lutea persisted until at least 30
      M, and characterized the post reproductive aging of F344/N females. The F344/N
      rats seem to resemble humans in that the cessation of estrous cycles occurs at
      approximately half their entire lifespan. However, other aging characteristics
      are unknown in postmenopausal women. Therefore, we must be careful when
      extrapolating the aging changes of reproduction in F344/N rats to human beings.

PMID- 17460360
TI  - Phenotypes of IRS-2 deficient mice produced by reproductive technology are
      stable.
AB  - We studied the impact of "IVF - ET" on the glucose tolerance test (GTT), insulin
      tolerance test (ITT) and adiponectin to investigate differences in the phenotypes
      of B6J- Irs2(-/-) mice. The B6J-Irs2(-/-) mice (KO-Nat group) were prepared by
      natural mating. Other mice were produced by IVF-ET used ICR strain recipients and
      surrogate mothers (KO-IVF group). Measurement of body weight, GTT, ITT and blood
      sampling were performed at the ages of 6, 14 and 24 weeks after birth. Body
      weights, impaired glucose tolerance, insulin resistance and plasma adiponectin
      concentrations did not differ for each gender between the KO-IVF and KO-Nat
      groups. Therefore, we concluded that phenotypes of Irs2(-/-) mice produced by
      reproductive technology are stable.

PMID- 17460361
TI  - Spontaneous peritoneal malignant mesothelioma in a geriatric japanese macaque
      (Macaca fuscata).
AB  - A 28.5-year-old female Japanese macaque (Macaca fuscata) was euthanatized because
      of abdominal distension due to severe ascites. Nodular lesions of varying sizes
      up to 5 mm in diameter were distributed diffusely on the surface of the omentum,
      mesentery and parietal peritoneum. No neoplastic masses were detected in any
      visceral organ. The nodules were composed of proliferation of mono- or multi
      layered epithelial-like cells occasionally showing papillary growth and sheets of
      small round or polygonal cells. Signet ring-like cells and tubular structures
      were occasionally present. Neoplastic cells were strongly positive to
      cytokeratin, and occasionally to vimentin. Based on gross and histopathological
      findings, this tumor was diagnosed as an epithelial type of peritoneal malignant
      mesothelioma, the first reported case in the non-human primates.

PMID- 17460362
TI  - Absence-like and tonic seizures in aspartoacylase/attractin double-mutant mice.
AB  - The Spontaneously Epileptic Rat (SER), a double-mutant for tremor and zitter
      mutations, shows spontaneous occurrences of absence-like and tonic seizures.
      Several lines of evidence suggest that the combined effect of Aspa and Atrn
      mutations is the most likely cause of the epileptic phenotype of the SER. To
      address this issue, we produced a new double-mutant mouse line carrying both
      homozygous Aspa-knockout and Atrn(mg-3J) mutant alleles. The Aspa/Atrn double
      mutant mice exhibited absence-like and tonic seizures that were characterized by
      the appearance of 5-7 Hz spike-wave-like complexes and low voltage fast waves on
      EEGs. These results demonstrate directly that the simultaneous loss of the Aspa
      and Atrn gene functions causes epileptic seizures in the mouse and suggest that
      both Aspa and Atrn deficiencies might be responsible for epileptic seizures in
      the SER.

PMID- 17460363
TI  - Re-establishment of complement C6-deficient rabbit colony by cryopreserved sperm
      transported from abroad.
AB  - Introducing rabbits as genetic materials into institutes for experimental animals
      from other colonies is essential for biomedical research. Currently, it is
      inconvenient to transport live rabbits from abroad, since they suffer from
      stress, are prone to accidents and must be inspected, as well as endure
      quarantine during the often long journey. To overcome these limitations of live
      animals, we transported sperm cryopreserved in liquid nitrogen. Rabbit sperm was
      collected from complement C6-deficient rabbits in Germany and then transported to
      Japan using a dry-shipper containing liquid nitrogen. After thawing the frozen
      semen and artificial insemination (AI), eleven live pups were born. Subsequently,
      a homozygous C6-deficient rabbit colony was established.

PMID- 17460364
TI  - The earlier, the better.

PMID- 17460365
TI  - Chymase and matrix metalloproteinase.

PMID- 17460366
TI  - Insulin resistance is associated with arterial stiffness independent of obesity
      in male adolescents.
AB  - To determine the relationship between insulin resistance (IR) and arterial
      stiffness independent of obesity in male adolescents, we evaluated body fat,
      lipid parameters, indices of IR (fasting insulin, and the homeostasis model
      assessment of insulin resistance [HOMA-IR]), indices of insulin sensitivity (IS)
      (fasting glucose/fasting insulin [GF/IF], and the quantitative insulin
      sensitivity check index [QUICKI]), and lifestyle parameters in 256 male
      adolescents. We divided the study group into the following four subgroups based
      on the median value of HOMA-IR and obesity: non-obese with IS, non-obese with IR,
      obese with IS, and obese with IR. In order to estimate arterial stiffness, we
      measured brachial ankle pulse wave velocity (baPWV). Despite having a high body
      mass index (BMI), obese-IS adolescents showed a significantly lower fasting
      insulin and baPWV, but had higher IS indices than non-obese-IR adolescents. After
      an adjustment for age, BMI, waist-to-hip ratio, mean blood pressure, heart rate,
      total cholesterol level, triglyceride, alanine aminotransferase (ALT) level,
      physical activity, and television and computer usage, multiple regression models
      showed that baPWV was independently correlated with IR and IS indices. In
      conclusion, our results demonstrate an association between IR and baPWV
      independent of weight, suggesting that IR is a risk factor for the development of
      early atherosclerosis. Interventions that decrease IR in addition to weight
      reduction may be necessary to alter the early development of cardiovascular risk.

PMID- 17460367
TI  - Noninvasive assessment of left atrial function by strain rate imaging in patients
      with hypertension: a possible beneficial effect of renin-angiotensin system
      inhibition on left atrial function.
AB  - Renin-angiotensin system (RAS) inhibitors are likely to reduce the development of
      atrial fibrillation by preventing atrial fibrosis. Strain rate (SR) imaging is a
      novel echocardiographic technique to quantify left atrial (LA) function. However,
      it has not been determined whether SR imaging is applicable for detection of LA
      dysfunction in hypertensive (HT) patients. We used SR imaging to assess
      alteration in LA function in HT patients and its modification by RAS inhibitors.
      SR imaging was performed in 80 HT patients and 50 age-matched normotensive (NT)
      subjects. HT patients were divided into two groups according to left ventricular
      hypertrophy (LVH) and LA dilatation. Peak SR was measured at each LA segment
      (septal, lateral, posterior, anterior, and inferior) and mean peak systolic SR
      (SR-LAs) was calculated by averaging data in each segment. Mean SR-LAs levels in
      the dilated LA group (1.97+/-0.45 s(-1), n=25) and non-dilated LA group (2.15+/
      0.57 s(-1), n=55) were significantly (p<0.05) lower than that in NT subjects
      (2.53+/-0.71 s(-1)). Irrespective of the presence or absence of LVH, mean SR-LAs
      in HT patients was lower than that in NT subjects. When RAS inhibitors were used,
      the mean SR-LAs level in the non-dilated LA group was equivalent to that in NT
      subjects. In HT patients, mean SR-LAs, an index of LA reservoir function,
      decreases before development of LA enlargement and LVH. Treatment with RAS
      inhibitors appears to preserve LA reservoir function in HT patients without
      dilated LA. SR imaging can detect LA dysfunction in HT patients and is useful for
      evaluation of the therapeutic benefit on LA reservoir function.

PMID- 17460368
TI  - Comparison of the effects of pioglitazone and metformin on insulin resistance and
      hormonal markers in patients with impaired glucose tolerance and early diabetes.
AB  - Impaired glucose tolerance (IGT) is associated with cardiovascular risk factors,
      but the effects of pioglitazone and metformin on IGT are not well described. We
      tested the hypothesis that each drug would exhibit antiatherogenic and anti
      inflammatory effects in subjects with IGT and early diabetes. The study design
      was a prospective, randomized, open label, cross-over study. Blood tests,
      including a 75-g oral glucose tolerance test (OGTT), were performed at baseline
      and after each treatment. Pioglitazone 15 mg/day or metformin 500-750 mg/day was
      given for 3 months. Biochemical markers to assess insulin resistance as well as
      lipid, inflammatory, neurohumoral, and hemostatic factors were included. Twenty
      five subjects (17 male, 8 female; age [mean+/-SD]: 61+/-9 years; 84%
      hypertensive) completed the protocol. Of 25 subjects, 14 were diagnosed as IGT
      and 11 as diabetes with 75-g OGTT. Pioglitazone significantly reduced fasting
      glucose (p<0.05), and homeostasis model assessment of insulin resistance (HOMA
      IR) (p<0.05) and metformin (p<0.01) reduced cholesterol. Both drugs significantly
      reduced aldosterone (both p<0.05) and von Willebrand factor (vWF) (both p<0.05).
      Plasma adiponectin was increased only by pioglitazone (p<0.001). Neither drug
      affected BP levels. In conclusion, pioglitazone was superior to metformin for the
      improvement of insulin resistance and adiponectin, and both drugs were equally
      effective in reducing vWF and aldosterone in subjects with IGT and early
      diabetes. Early intervention with pioglitazone or metformin therapy may reduce
      the incidence of future cardiovascular disease in subjects with impaired glucose
      tolerance or early diabetes.

PMID- 17460369
TI  - Angiotensin-converting enzyme gene 2350 G/A polymorphism is associated with left
      ventricular hypertrophy but not essential hypertension.
AB  - The angiotensin-converting enzyme (ACE) gene (ACE) is one of the most studied
      candidate genes related to essential hypertension (EH) and left ventricular
      hypertrophy (LVH). ACE rs4343 synonymous coding polymorphism (2350 G/A) is known
      among the polymorphisms of this gene to have the most significant effect on
      plasma ACE concentrations. The aim of the present study was to investigate the
      association of this polymorphism with EH and LVH in 440 subjects (246 EH patients
      and 194 controls) from a Chinese Han population. In this study, 2350 G/A
      genotypes were identified by polymerase chain reaction and restriction digestion
      in all study participants, and left ventricular mass was assessed by 2-mode
      echocardiography in 178 untreated EH patients. There was no significant
      difference in either genotype distribution (p=0.3659) or allele frequency
      (p=0.1453) between EH and control groups. In addition, the 2350 G/A polymorphism
      had no effect on blood pressure in either controls or untreated EH patients. The
      distribution of genotypes differed significantly when patients with LVH were
      examined, i.e., 14.71% GG, 54.41% GA, and 30.88% AA patients had this
      complication, and 36.36% GG, 42.73% GA, and 20.91% AA patients did not
      (p=0.0070). The LVH patients had a higher A allele frequency (58.09%) than
      patients without LVH (42.27%) (p=0.0037). Logistic regression analysis revealed
      that the association between the A allele and LVH was independent of age, blood
      pressure, and body mass index. The relative risk of LVH in patients bearing the A
      allele (GA+AA group) compared with that of GG hypertensive patients was 3.31 (95%
      confidence interval [CI]: 1.43 to 7.68). These findings suggest an association
      between LVH and the 2350A allele in hypertensive patients.

PMID- 17460370
TI  - Renoprotective effect and cost-effectiveness of using benidipine, a calcium
      channel blocker, to lower the dose of angiotensin receptor blocker in
      hypertensive patients with albuminuria.
AB  - In hypertensive patients with chronic renal disease, angiotensin receptor
      blockers (ARBs) are among the first-line drugs, and calcium channel blockers
      (CCBs) are recommended as a second line. We examined the effects of two
      therapeutic strategies using ARBs and benidipine, a CCB, on blood pressure (BP),
      urinary albumin excretion (UAE), and cost-effectiveness in hypertensive patients
      with albuminuria. Patients whose BP was 140/90 mmHg or higher despite treatment
      with low- or medium-dose ARBs were assigned randomly to two groups. In Group A
      (n=14), the ARB dose was maximized and then benidipine was added until BP targets
      were reached (<130/85 mmHg). In Group B (n=18), benidipine was administered first
      and then the ARB dose was increased until BP targets were reached. The BP targets
      were achieved by ARB alone in 36% of Group A patients and by the addition of
      benidipine in 83% of Group B patients. Finally, BP decreased in each group,
      reaching the targets in 93% of Group A patients and 94% of Group B patients after
      a 4-month therapeutic period. UAE was decreased in both groups after a 4-month
      therapeutic period compared to the allocation period (-33+/-6% in Group A, -31+/
      6% in Group B; p<0.001, respectively). The monthly drug cost was higher (11,426+/
      880 vs. 8,955+/-410 yen, p=0.012) and the cost-effectiveness of antihypertensive
      treatment was lower (p=0.003) in Group A than in Group B. We conclude that the
      addition of benidipine to low- or medium-dose ARB is, in light of the renal
      protection and the cost-effectiveness of this approach, a useful therapeutic
      strategy for controlling BP in hypertensive patients with albuminuria.

PMID- 17460371
TI  - Effects of telmisartan and losartan on insulin resistance in hypertensive
      patients with metabolic syndrome.
AB  - Partial peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists
      are known to decrease insulin resistance. Experimental studies have shown that
      the angiotensin type 1 receptor blocker (ARB) telmisartan has a PPAR-gamma
      activating property, but there does not appear to be a class effect. To test
      telmisartan's clinical importance, we here investigated its effect on insulin
      resistance in hypertensive patients with metabolic syndrome (MetS) in comparison
      with another ARB, losartan. A total of 42 hypertensive MetS patients (29 female,
      13 male) were included (mean age: 50+/-9, range: 20-70 years). NCEP-ATP III
      criteria were used for the diagnosis of MetS. Patients were randomized to receive
      either telmisartan 80 mg/day (n=21) or losartan 50 mg/day (n=21) for 8 weeks.
      Biochemical assessments were made at baseline and at the end of the 8 weeks.
      Insulin resistance was evaluated by using homeostasis model assessment of insulin
      resistance (HOMA-IR). Both groups had similar reductions in systolic and
      diastolic pressures (p>0.05). HOMA-IR did not change significantly in either
      group throughout the study. In the telmisartan group, the mean HOMA-IR at
      baseline and at the end of the study were 1.9+/-07 and 1.9+/-0.5, respectively.
      The figures for the losartan group were 1.8+/-0.6 and 1.8+/-0.6, corresponding.
      In conclusion, in contrast with the reports that telmisartan may decrease insulin
      resistance by an effect associated with its molecular structure, 8 weeks of
      telmisartan treatment in the present study had a neutral effect on insulin
      resistance in hypertensive MetS patients, and similar results were obtained for
      losartan.

PMID- 17460372
TI  - Changes in the demographics and prevalence of chronic kidney disease in Okinawa,
      Japan (1993 to 2003).
AB  - To compare the risk factor demographics and the prevalence of chronic kidney
      disease (CKD), we analyzed two databases from the 1993 (N=143,948) and 2003
      (N=154,019) mass screenings in Okinawa, Japan (Okinawa General Health Maintenance
      Association registry). We estimated the glomerular filtration rate (GFR) using
      serum creatinine (SCr) levels. SCr was measured by the modified Jaffe method in
      1993 and by enzyme assay in 2003; the relation between the two methods was: SCr
      (Jaffe) = 0.194 + 1.079 x SCr (enzyme). CKD prevalence was compared using the
      estimated GFR calculated by the abbreviated Modification of Diet in Renal Disease
      (MDRD) equation. SCr was measured in 66.2% (1993) and 69.8% (2003) of the total
      screenees. Proteinuria was present in 3.4% (1993) and 4.3% (2003) of the total
      screened population, respectively. The prevalence of CKD (GFR<60 ml/min/1.73
      m(2)) was similar between the two databases, being 15.7% in 1993 and 15.1% in
      2003. However, the demographics of the CKD risk factors changed during the study
      period. The mean level of systolic blood pressure decreased, whereas the
      prevalence of obesity and the mean levels of serum cholesterol and fasting plasma
      glucose increased. In 2003, the estimated prevalence of metabolic syndrome in the
      general population of Japan calculated using the modified National Cholesterol
      Education Program (NCEP) criteria was 19.1%. The prevalence of CKD was
      significantly associated with that of metabolic syndrome: the age- and sex
      adjusted odds ratio was 1.332 (95% confidence interval [CI], 1.277-1.389;
      p<0.0001). In conclusion, the demographics of the participants of the general
      screenings in Okinawa, Japan differed between the 1993 and 2003 screenings, but
      the prevalence of CKD seemed to be similar, or at least did not increase
      substantially, between the two databases.

PMID- 17460373
TI  - Developmental activity of the renin-angiotensin system during the "critical
      period" modulates later L-NAME-induced hypertension and renal injury.
AB  - The incidence of hypertension and hypertensive renal disease is increasing
      worldwide, and new strategies to prevent these diseases need to be investigated.
      The aims of this study were 1) to examine if transient exposure to an angiotensin
      receptor blocker (ARB) during an early period in hypertension development confers
      protection against subsequent worsening of hypertension and renal injury induced
      by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and 2)
      conversely, to examine the effects of transient exposure to angiotensin II (Ang
      II) during the same period. First, spontaneously hypertensive rats (SHR) were
      treated transiently from age 3 to 10 weeks with an ARB (candesartan cilexetil), a
      calcium channel antagonist or a vasodilator, then taken off treatment for 2
      months. Administration of L-NAME at age 18 weeks caused severe hypertension and
      renal injury. However, the rats that had been exposed to the ARB not only had a
      lower blood pressure, but also failed to show signs of renal injury or increase
      of oxidative stress. Furthermore, the elevation of components of the renin
      angiotensin-aldosterone system was also suppressed in these rats. In the second
      study, Wistar-Kyoto rats (WKY) and SHR were exposed to Ang II from age 4 to 8
      weeks. The follow-up showed that the blood pressures in the WKY remained elevated
      compared to controls, while the SHR had heightened increases in blood pressure,
      renal renin mRNA, and urinary 8-hyroxydeoxyguanosine after L-NAME administration.
      Together, these experiments demonstrate that transient treatment of rats during
      an early phase in the development of hypertension with an ARB suppresses the
      renin-angiotensin-aldosterone system and confers long-term protection against
      subsequent L-NAME-induced renal injury and increases in renal oxidative stress.
      Conversely, developmental exposure to Ang II during this "critical" period had
      the opposite effect, predisposing rats to higher blood pressure, renal injury,
      and oxidative stress after L-NAME administration.

PMID- 17460374
TI  - The effects of chymase on matrix metalloproteinase-2 activation in neointimal
      hyperplasia after balloon injury in dogs.
AB  - Chymase is known to generate angiotensin II in the vascular wall. In this study
      we investigated a novel role for chymase other than angiotensin II production in
      vascular proliferation after balloon injury. Chymase promoted the migration of
      vascular smooth muscle cells in the matrix-coated invasion chambers and activated
      promatrix metalloproteinase-2 obtained from the culture medium of vascular smooth
      muscle cells. Two weeks after balloon injury, significant neointimal formation
      was found in dog carotid arteries. After injury, active matrix metalloproteinase
      2 was increased in parallel with the augmentation of chymase activity that was
      seen in the proliferating region of the vascular wall. The oral administration of
      NK3201 (1 mg/kg per day), a chymase inhibitor, prevented neointimal formation and
      significantly suppressed both active matrix metalloproteinase-2 and chymase
      activities 2 weeks after injury. These results suggest that chymase inhibitors
      can prevent the development of intimal hyperplasia via the inhibition of matrix
      metalloproteinase-2 activation in balloon-injured arteries.

PMID- 17460375
TI  - Gene delivery of paraoxonase-1 inhibits neointimal hyperplasia after arterial
      balloon-injury in rabbits fed a high-fat diet.
AB  - Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL)-associated enzyme that
      hydrolyzes oxidized phospholipids, thereby preventing the oxidative modification
      of low-density lipoproteins (LDL). A high-fat diet reduces PON-1 activity,
      enhancing LDL oxidation. Thus, PON-1 is a candidate for anti-atherogenic gene
      therapy. In the present study, we investigated the effect of local PON-1
      overexpression on the development of atherosclerotic lesions using the Sendai
      virus-mediated transgenic technique. One-month-old rabbits (n=11) were fed a high
      fat diet for 8 weeks and then subjected to balloon injury of the common iliac
      artery and simultaneous infection with a Sendai virus vector containing the PON-1
      gene (n=7) or enhanced green fluorescence protein (EGFP) gene as a control (n=4).
      The arteries were examined 7-10 days after the operation. Local overexpression of
      PON-1 almost completely eliminated the immunohistochemical signals of the lectin
      like oxidized LDL receptor-1 (LOX-1), thereby inhibiting macrophage accumulation,
      intimal thickening (by 63% compared with control), or atherosclerotic plaque
      formation in the vascular lumen (by 87.5%). Decreased levels of oxidative stress
      in the PON-1-treated arteries were confirmed by 4-hydroxy-2-nonenal (HNE)
      staining. Local overexpression of PON-1 in the arteries attenuated oxidative
      stress, thereby inhibiting the atherosclerotic process. Delivery of the PON-1
      gene may be a possible therapeutic strategy for preventing atherosclerosis.

PMID- 17460376
TI  - Arterial blood pressure and renal sodium excretion in dopamine D3 receptor
      knockout mice.
AB  - Alterations in the dopaminergic system may contribute to the development of
      hypertension. Recently, it has been reported that pentobarbital-anesthetized mice
      with deficient dopamine D(3) receptors showed renin-dependent elevation in blood
      pressure. In a series of experiments, we evaluated the contribution of the
      dopamine D(3) receptor to the renal sodium excretion and arterial blood pressure
      behavior in conscious as well as anesthetized dopamine D(3) receptor knockout (-/
      ) mice. The blood pressure measuring study was designed as a cross-over trial to
      investigate the influence of different sodium loads. The animals were fed a
      normal salt diet (0.6% NaCl, NS) for 1 week and afterwards a low (0.2% NaCl, LS)
      or a high salt diet (4.6% NaCl, HS) for 2 weeks. After the third week, the
      animals were switched to the corresponding protocol. Systolic blood pressure in
      conscious (-/-) mice measured by tail-cuff plethysmography was not different from
      that of wild-type (+/+) animals, irrespective of the time course or the salt
      diet. In another experiment, challenge of an acute sodium loading per gavage in
      conscious D(3) receptor (-/-) and (+/+) animals on HS or NS diet did not show
      significant differences in renal sodium excretion between the two genotypes.
      Additionally, animals were fed an NS diet for 1 week and an HS diet for another
      week. As expected, sodium excretion significantly increased after the change from
      the NS to the HS diet. A slightly lower urinary sodium excretion was observed
      when comparing D(3) receptor (-/-) mice to their corresponding (+/+) mice, both
      on an HS diet. Clearance experiments with anesthetized D(3) receptor (-/-) and
      (+/+) mice were performed to investigate the renal sodium excretion capacity,
      when exposed to a moderate volume expansion (VE). Urinary sodium excretion
      increased in response to the VE; however, no difference were observed between the
      two genotypes. Taking these results together, we conclude that in the present
      animal model renal dopamine D(3) receptors are not significantly involved in the
      regulation of blood pressure associated with a deficiency in renal sodium
      elimination.

PMID- 17460377
TI  - Is primary aldosteronism rare or common among hypertensive patients?

PMID- 17460378
TI  - Inflammation and salt sensitivity in the early state of hypertension.

PMID- 17460379
TI  - Pleiotropic actions of angiotensin receptor antagonists.

PMID- 17460380
TI  - Prevalence of primary aldosteronism among unselected hypertensive patients: a
      prospective study based on the use of an aldosterone/renin ratio above 25 as a
      screening test.
AB  - Primary aldosteronism (PA) has been considered a rare cause of hypertension. The
      introduction of the aldosterone/renin ratio (ARR) as a screening test has led to
      an increase in the detection rate. The aim of this study was to evaluate the
      prevalence of PA among unselected hypertensive patients by using an ARR >25 as a
      screening test. We studied 3,000 consecutive unselected hypertensive patients.
      Blood samples for the determination of plasma renin activity (PRA), aldosterone
      (ALD) and electrolytes were drawn in the morning, and patients with an ARR >25
      underwent intravenous saline infusion as a confirmatory test. Adrenal CT and a
      dexamethasone suppression test were performed in patients with confirmed PA.
      Patients with a positive dexamethasone test underwent genetic testing for
      glucocorticoid-remediable aldosteronism (GRA). Out of 3,000 hypertensives, 684
      (22.8%) showed an ARR >25 and 177 of them (5.9% of the whole population) had a
      positive saline loading test. Only 44 of them (24.8%) were hypokalemic. CT was
      performed in all the patients with confirmed PA and 53 of them (29.9%) had a
      solitary adrenal macroadenoma, 112 (63.3%) had bilateral adrenal enlargement and
      12 (6.8%) had normal appearing adrenal glands. Of 177 patients given
      dexamethasone to identify GRA, 8 (4.5%) showed aldosterone suppression but only
      one (0.1%) tested positive for the chimeric gene. In conclusion, our findings
      indicate that standardized application of an ARR >25 to unselected hypertensive
      patients, followed by i.v. saline loading as a confirmatory test, can result in
      the detection of a large number of patients with PA (5.9% of the studied
      population), most of whom are normokalemic. Bilateral adrenal hypertrophy
      represents the more common form of PA.

PMID- 17460381
TI  - Effects of hypertension and type 2 diabetes mellitus on the risk of total
      cardiovascular events in Japanese patients with hypercholesterolemia:
      implications from the Japan Lipid Intervention Trial (J-LIT).
AB  - Hyperlipidemia, hypertension, and diabetes mellitus (DM) are well-established
      risk factors for cardiovascular disease. We analyzed the cardiovascular events in
      hyperlipidemic patients with or without DM who were administered open-labeled
      simvastatin in groups stratified by blood pressure level using data from the
      Japan Lipid Intervention Trial (J-LIT). Hyperlipidemic patients with DM (n=6,288)
      had significantly more cardiovascular events than those without DM (n=33,933).
      The incidence rates of total cardiovascular events in the Non-DM and DM groups
      were 15.40 and 25.76 per 1,000 patients for the 6-year period, respectively. The
      relative risk of total cardiovascular events in the DM vs. the Non-DM group was
      1.68, and the relative risk was significantly higher in the DM than in the Non-DM
      group. The relative risks of total cardiovascular events were significantly
      higher in DM and Non-DM patients whose systolic blood pressure (SBP) was greater
      than or equal to 130 mmHg compared to that of Non-DM patients whose SBP was less
      than 130 mmHg, and in DM and Non-DM patients whose diastolic blood pressure (DBP)
      was greater than or equal to 80 mmHg compared to that of Non-DM patients whose
      DBP was less than 80 mmHg. In all groups stratified by SBP and DBP, relative
      risks of total cardiovascular events were higher in DM patients than in Non-DM
      patients. For patients with hypercholesterolemia and DM, blood pressure should be
      strictly controlled in order to prevent both coronary events and stroke. These
      results are in good agreement with the JNC 7 and the ESH/ESC guidelines for DM
      patients, which recommended that the SBP and DBP be less than 130 and 80 mmHg,
      respectively.

PMID- 17460382
TI  - High-density lipoprotein cholesterol and insulin resistance are independent and
      additive markers of left ventricular hypertrophy in essential hypertension.
AB  - We examined whether plasma high-density lipoprotein-cholesterol (HDL-C) levels
      and glucose metabolism parameters are independent or additive predictors of left
      ventricular hypertrophy (LVH) in patients with untreated essential hypertension.
      The study group consisted of 41 Japanese patients with untreated essential
      hypertension and LVH (left ventricular mass index [LVMI] >125 g/m2; age 58+/-6
      years, mean+/-SD), and the control group consisted of 39 age-matched patients
      with untreated essential hypertension without LVH (LVMI <or=125 g/m2; age 58+/-7
      years). The following metabolic parameters were higher in the group with LVH:
      fasting plasma glucose (FPG) (p<0.01), fasting insulin concentration (F-IRI)
      (p<0.0001), and homeostasis model assessment (HOMA)-index (p<0.0001). Among the
      laboratory parameters investigated, plasma HDL-C levels were lower (p<0.0001),
      and triglyceride and uric acid levels were higher in the group with LVH (p<0.05
      for both). The nighttime systolic and diastolic ambulatory blood pressure (ABP)
      (p<0.0001, p<0.01, respectively) and nighttime heart rate (p<0.01) were higher in
      patients with LVH. Multivariate logistic analysis identified HDL-C (odds ratio
      [OR]=0.92, 95% confidence interval [CI]=0.87-0.98, p<0.05), HOMA-index (OR=3.83,
      95% CI=1.28-11.5, p<0.05) and nighttime systolic ambulatory blood pressure (ABP)
      (OR=1.06, 95% CI=1.00-1.13, p<0.05) as independent significant risk factors for
      LVH. Our findings suggest that HDL-C, HOMA-index and nighttime systolic ABP are
      independent predictors for the presence of LVH in Japanese patients with
      essential hypertension.

PMID- 17460383
TI  - Circulating endothelial progenitor cells, C-reactive protein and severity of
      coronary stenosis in Chinese patients with coronary artery disease.
AB  - We sought to investigate whether numbers and activity of circulating endothelial
      progenitor cells (EPCs) correlate with severity of coronary stenosis as well as
      cardiovascular risk factors in patients with stable coronary artery disease
      (CAD). Number of circulating EPCs was analyzed in 104 consecutive patients with
      proven or clinically suspected CAD. Adhesive and migratory activity was also
      determined. The number of EPCs was lower in patients with a single diseased
      coronary artery (Group II, n=35, p<0.05 vs. Group I) or multiple diseased
      arteries (Group III, n=25, p<0.01 vs. Group I, p<0.05 vs. Group II) compared to
      those with normal coronary arteries (Group I, n=44). The number of EPCs was also
      related with angiographic Gensini score (r=-0.355, p=0.006). In addition,
      concentrations of C-reactive protein (CRP) were elevated in patients with CAD,
      and positively correlated with Gensini score (r=0.476, p=0.001). As for the risk
      factors, the number of EPCs was also inversely correlated with age (p=0.001),
      high sensitivity-CRP (p=0.012), hypertension (p=0.042) and family history of CAD
      (p=0.043). Most importantly, the migratory capacity of EPCs was compromised in
      patients with CAD, and inversely correlated with the angiographic Gensini score
      (r=-0.315, p=0.021). EPCs isolated from patients with CAD also showed an impaired
      adhesive activity (p<0.05). In conclusion, in patients with stable CAD, reduction
      in the number and impairment in the function of circulating EPCs were correlated
      with the severity of coronary stenosis. CRP may play an important role in
      reducing the number of EPCs and accelerating atherosclerosis. Given the important
      role of EPCs in neovascularization of ischemic tissue, a decrease in the number
      and activity of EPCs may contribute to the impaired vascularization in patients
      with CAD.

PMID- 17460384
TI  - Masked nocturnal hypertension and target organ damage in hypertensives with well
      controlled self-measured home blood pressure.
AB  - It has been reported that masked hypertension, a state in which patients show
      normal clinic blood pressure (BP) but elevated out-of-clinic BP by self-measured
      home BP, is a predictor of cardiovascular morbidity much like sustained
      hypertension. In addition, nocturnal BP is closely associated with cardiovascular
      disease. This might mean that ambulatory and self-measured home BP monitoring
      each provide independent information. We performed ambulatory BP monitoring, self
      measured home BP monitoring, echocardiography and carotid ultrasonography in 165
      community-dwelling subjects. We subclassified the patients according to the
      ambulatory and self-measured home BP levels as follows: in the masked nocturnal
      hypertension group, the self-measured home BP level was <135/85 mmHg and the
      ambulatory nocturnal BP level was >or=120/75 mmHg; in the normotensive group, the
      self-measured home BP level was <135/85 mmHg and the ambulatory nocturnal BP
      level was <120/75 mmHg. The intima-media thickness (IMT) and relative wall
      thickness (RWT) were greater in the masked nocturnal hypertension group than in
      the normotensive group (IMT: 0.76+/-0.20 vs. 0.64+/-0.14 mm, p<0.05; RWT: 0.50+/
      0.14 vs. 0.41+/-0.10, p<0.05). Even in hypertensives with well-controlled self
      measured home BP, elevated ambulatory nocturnal BP might promote target organ
      damage. We must rule out masked hypertension using self-measured home BP
      monitoring, and we might also need to rule out nocturnal masked hypertension
      using ambulatory BP monitoring.

PMID- 17460385
TI  - Alterations in placental growth factor levels before and after the onset of
      preeclampsia are more pronounced in women with early onset severe preeclampsia.
AB  - It has been established that the serum placental growth factor (PlGF) decreases
      and the soluble fms-like tyrosine kinase-1 (sFlt-1) increases in women with
      preeclampsia. However, there have been no studies on the relation between
      preeclampsia onset time and the changes in PlGF and sFlt-1. Furthermore, the PlGF
      and sFlt-1 levels have not been evaluated using their reference values specific
      to each gestational age. In this study we reevaluated the serum PlGF and sFlt-1
      levels before and after the clinical manifestation of early and late onset severe
      preeclampsia using the new reference values developed in our recent longitudinal
      study. Blood specimens were obtained immediately after the clinical manifestation
      of severe preeclampsia in 34 referred women, and both before and after the
      clinical manifestation in 8 women receiving a routine checkup at our institute.
      Both women with early and those with late preeclampsia showed decreased PlGF and
      increased sFlt-1 levels compared to normotensive controls at 28 and 37 weeks
      (n=68). However, those with early onset preeclampsia had a higher incidence of
      low PlGF (<5th percentile on the reference values) and high sFlt-1 (>or=95th
      percentile) than those with late onset (low PlGF: 93% vs. 55%; high sFlt-1: 100%
      vs. 60%). log10PlGF (r=0.574, p<0.001) and log10(sFlt-1/PlGF) (r=-0.556, p<0.001)
      were correlated with the week of onset of preeclampsia. Before the onset of
      preeclampsia, the incidence rate of low PlGF in the women with early onset
      preeclampsia was 100% (5/5), whereas that in the women with late onset
      preeclampsia was 0% (0/2) (p=0.048). Therefore, alterations in the PlGF levels
      both before and after the onset of preeclampsia may be more pronounced in women
      with early onset than those with late onset severe preeclampsia.

PMID- 17460386
TI  - Benidipine attenuates glomerular hypertension and reduces albuminuria in patients
      with metabolic syndrome.
AB  - Recent studies have shown that metabolic syndrome is associated with an increased
      risk for chronic kidney disease. We recently found that the prevalence of sodium
      sensitive hypertension in patients with metabolic syndrome was significantly
      higher than that in patients with essential hypertension but without metabolic
      syndrome. We therefore assessed the effects of benidipine, a long-acting calcium
      channel blocker, on the sodium sensitivity of blood pressure and renal
      hemodymamics in 5 patients with metabolic syndrome. Glomerular hemodynamics were
      assessed using pressure-natriuresis curves, which were constructed by plotting
      the urinary excretion of sodium as a function of the mean arterial pressure,
      which was calculated as the mean of 48 values based on 24-h monitoring, during
      the intake of low (3 g NaCl daily) and relatively high (10 g NaCl daily) sodium
      diets. Under the relatively high sodium diet condition, benidipine significantly
      lowered systolic and diastolic blood pressure. The pressure-natriuresis curve was
      steeper after the administration of benidipine. Benidipine lowered glomerular
      capillary hydraulic pressure (P(GC)) levels (from 54.4+/-7.5 to 47.0+/-7.0 mmHg,
      p=0.0152) and reduced both the resistance of the afferent arterioles (from
      10,338+/-2,618 to 9,026+/-2,627 dyn.s/cm5, p=0.047) and the resistance of the
      efferent arterioles (from 4,649+/-2,039 to 2,419+/-2,081 dyn.s/cm(5), p=0.003).
      The urinary albumin excretion rate also decreased after the administration of
      benidipine. These findings indicated that benidipine may be effective for
      reducing the risk of developing chronic kidney disease in patients with metabolic
      syndrome.

PMID- 17460387
TI  - Risk of developing low glomerular filtration rate or elevated serum creatinine in
      a screened cohort in Okinawa, Japan.
AB  - There are no known predictors of renal dysfunction, particularly for a community
      based screening. We evaluated the changes in serum creatinine (SCr) and
      glomerular filtration rate (GFR) among screenees who participated in the
      screening program of the Okinawa General Health Maintenance Association both in
      1983 and 1993. A total of 4,662 screenees at least 30 years of age at the 1983
      screening were analyzed to examine whether they developed high SCr (>or=1.4 mg/dl
      for men, >or=1.2 mg/dl for women) or low GFR (<60 ml/min/1.73 m2). Overall, mean
      GFR (mean+/-SD) decreased slightly from 72.7+/-11.7 ml/min/1.73 m2 to 70.8+/-15.0
      ml/min/1.73 m2. In 1983, the prevalences of high SCr and low GFR were 3.6% and
      13.2%, respectively, and in 1993, they were 8.1% and 24.2%, respectively. Among
      the variables studied, dipstick proteinuria was the strongest predictor: the
      adjusted odds ratio (95% CI) was 1.282 (1.076-1.527, p<0.01) for high SCr and
      1.215 (1.116-1.322, p<0.01) for low GFR. Dipstick proteinuria was best for
      detecting subjects who might develop low GFR in a screening setting. In subjects
      without proteinuria, systolic blood pressure was a significant predictor for low
      GFR (the adjusted odds ratio [95% CI] was 1.015 [1.009-1.020, p<0.01]) and for
      high SCr (the adjusted odds ratio [95% CI] was 1.028 [1.016-1.040, p<0.01]). In
      conclusion, the present study suggests that a dipstick urine test for proteinuria
      and both systolic and diastolic blood pressure are useful to identify those who
      are at risk of developing high SCr and low GFR and consequently end-stage renal
      disease.

PMID- 17460388
TI  - Isohumulones derived from hops ameliorate renal injury via an anti-oxidative
      effect in Dahl salt-sensitive rats.
AB  - Previous studies have reported that isohumulones, the bitter compounds in beer,
      improve insulin resistance and hyperlipidemia in several animal models. In this
      study, we examined whether isohumulones ameliorate renal injury. Dahl salt
      sensitive hypertensive rats were fed a low-salt diet (LS), a high-salt diet (HS)
      or a high-salt diet containing 0.3% isohumulones (HS+IH) for 4 weeks. Urinary
      nitrite/nitrate (NOx) excretion was measured at 4 weeks along with blood pressure
      and urinary protein excretion. Renal injury was evaluated histologically and
      reactive oxygen species (ROS) and nitric oxide (NO) production in the renal
      cortex was visualized. Oxidative stress and NO synthase (NOS) expression were
      evaluated by immunohistochemical staining and Western blot analysis. Mean blood
      pressure was significantly decreased in the HS+IH group compared with the HS
      group at 4 weeks (158.1+/-8.7 vs. 177.5+/-3.7 mmHg; p<0.05). Isohumulones
      prevented the development of proteinuria in the HS+IH group compared with the HS
      group at 2 weeks (61.7+/-26.8 vs. 117.2+/-9.8 mg/day; p<0.05). Glomerulosclerosis
      and interstitial fibrosis scores were significantly decreased in the HS+IH group
      compared with the HS group (0.61+/-0.11 vs. 1.55+/-0.23, 23.7+/-6.8 vs. 36.1+/
      3.5%; p<0.05 for both). In the HS group, increased ROS and decreased NO were
      observed in glomeruli in vivo. Isohumulones reduced the ROS production, leading
      to the restoration of bioavailable NO. Urinary NOx excretion was significantly
      increased in the HS+IH group compared with the HS group. Furthermore, renal
      nitrotyrosine was increased in the HS group compared with the LS group, and this
      effect was prevented by isohumulones. Renal NOS expression did not differ among
      the three groups. These results suggest that isohumulones may prevent the
      progression of renal injury caused by hypertension via an anti-oxidative effect.

PMID- 17460389
TI  - The monocyte chemotactic protein-1 gene may contribute to hypertension in Dahl
      salt-sensitive rats.
AB  - In a previous study, we performed a genome-wide quantitative trait loci (QTLs)
      analysis for blood pressure using F2 rats derived from Dahl salt-sensitive (DS)
      and Lewis (LEW) rats and identified two QTLs that influenced blood pressure
      levels. Although we determined that one of the causative genes in the chromosome
      (Ch) 1 region seemed to be Klk1, we did not perform detailed analyses on the Ch10
      QTL region. The purpose of the present study was to identify candidate genes that
      influence blood pressure in the Ch10 QTL region. Using microarray analysis, we
      compiled a list of the genes that are differentially expressed between the two
      strains and that were localized to the Ch10 QTL region. Subsequent reverse
      transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis
      identified that, while the expression levels of Ccl2 mRNA were not different
      between the kidneys of DS and LEW rats fed a normal diet, those in DS were 10
      fold higher than those in LEW under a high-salt diet. Although the promoter
      reporter assay failed to identify causative nucleotide changes that led to the
      differential expression, monocyte chemotactic protein-1 (MCP-1) release from
      isolated monocytes were significantly higher in DS than in LEW. Intriguingly,
      this Ch10 QTL for blood pressure was also a possible QTL for urinary albumin
      excretion. Since Ccl2 is well known to be involved in various types of renal
      injury, it is likely that a higher expression of Ccl2 might aggravate macrophage
      infiltration, which in turn could aggravate tubulointerstitial injury, and
      thereby accelerate salt-sensitive hypertension. Thus, Ccl2 appears to be a
      interesting candidate gene for salt-sensitive hypertension in DS.

PMID- 17460390
TI  - Angiotensin II-induced regulation of the expression and localization of iron
      metabolism-related genes in the rat kidney.
AB  - Due to recent discoveries of novel genes involved in iron metabolism, our
      understanding of the molecular mechanisms underlying iron metabolism has
      dramatically increased. We have previously shown that the administration of
      angiotensin II alters iron homeostasis in the rat kidney, which may in turn
      aggravate angiotensin II-induced renal damage. Here we have investigated the
      effect of angiotensin II administration on the localization and expression of
      transferrin receptor (TfR), divalent metal transporter 1 (DMT1), ferroportin 1
      (FPN), and hepcidin mRNA in the rat kidney. Weak expression of TfR, DMT1, FPN,
      and hepcidin mRNA was observed in the kidneys of control rats. In contrast, after
      7 days of angiotensin II infusion by osmotic minipump, the expression of these
      mRNAs was more widely distributed. Staining of serial sections revealed that
      some, but not all, of the renal tubular cells positive for these genes contained
      iron deposits in the kidney of angiotensin II-infused animals. Real-time
      polymerase chain reaction (PCR) showed that the mRNA expression of TfR, iron
      responsive element-negative DMT1, FPN, and hepcidin mRNA increased ~1.9-fold,
      ~1.7-fold, ~2.3-fold, and ~4.7-fold, respectively, after angiotensin II infusion
      as compared with that of untreated controls, and that these increases could be
      suppressed by the concomitant administration of losartan. Our data demonstrate
      that these genes were unequivocally expressed in the kidney and could be
      regulated by angiotensin II infusion. The relative contribution, if any, of these
      genes to renal and/or whole-body iron homeostasis in various disorders in which
      the renin angiotensin system is activated should be investigated in future
      studies.

PMID- 17460391
TI  - Androgen induces production of male effect pheromone in female goats.
AB  - Previously we showed that the primer pheromone responsible for the "male effect"
      was produced in specific skin regions of castrated male goats by androgen
      treatments. In the present study, we examined whether androgen can also induce
      production of the male effect pheromone in female goats. Capsules containing
      dihydrotestosterone (DHT) or testosterone (T) were subcutaneously implanted into
      six ovariectomized (OVX) goats for 28 days. Small skin samples were collected
      from the head and rump regions, and the pheromone activity of their ether
      extracts was examined using a bioassay that monitors the electrophysiological
      manifestation of the hypothalamic gonadotropin-releasing hormone pulse generator
      as multiple-unit activity. Behaviors of OVX goats towards ovary-intact estrous
      goats were also examined before and at the end of DHT or T treatment. Before
      androgen treatment, neither the head nor rump skin samples in OVX goats showed
      pheromone activity. DHT treatment induced pheromone activity in the head skin
      sample of six OVX goats and in the rump skin sample of two OVX goats. Similar
      results were obtained by T treatment. In addition, OVX goats treated with T
      showed masculine-type sexual behaviors such as courtship and mounting behaviors
      towards the estrous goats. These results demonstrate that androgen is capable of
      inducing primer pheromone activity in the female and suggest that the synthesis
      pathway of the male effect pheromone exists in both sexes in the goat.

PMID- 17460392
TI  - Vitrification of immature bovine oocytes by the microdrop method.
AB  - This study was conducted to determine the optimal vitrification conditions for
      immature bovine oocytes using the microdrop method. In experiment 1, the optimal
      pre-equilibration period for microdrop vitrification was examined. The maturation
      rate of vitrified oocytes with a 3 min first pre-equilibration period (41.1%) was
      higher than that of vitrified oocytes with a 0 min first pre-equilibration period
      (21.4%), and the values of those with a 1 (33.9%) or 5 min (27.4%) first pre
      equilibration period were intermediate. The value for a 1 min second pre
      equilibration period (44.4%) was significantly higher (P<0.05) than those for a
      0.5 (28.6%) and 2 min (21.4%) second pre-equilibration period. In experiment 2,
      the distribution of microtubules in matured oocytes was investigated. There was
      no difference among the first pre-equilibration times in terms of the rates of
      normal spindles in vitrified oocytes. However, this value was significantly
      higher (P<0.05) in the 1 min group (52.8%) compared with the 0.5 (16.7%) and 2
      min groups (12.3%). In experiment 3, we investigated the developmental capacity
      of immature bovine oocytes vitrified under optimal pre-equilibration conditions
      (3 min and 1 min for the first and second pre-equilibrations, respectively).
      Although the total fertilization rates were significantly lower (P<0.05) in the
      vitrified oocytes (65.6%) compared with the control oocytes (92.4%), there was no
      difference in the rate of normal fertilization (2PN) between the vitrified
      (78.6%) and control (82.0%) oocytes. Cleavage and blastocyst rates were
      significantly lower (P<0.05) in vitrified oocytes (55.7 and 2.3%) than in control
      oocytes (84.4 and 34.7%). Thus, these results indicated that immature bovine
      oocytes can survive after microdrop vitrification and subsequently can be
      cultured to mature oocytes capable of undergoing fertilization in vitro and
      developing into blastocysts.

PMID- 17460393
TI  - Endothelin-1 induces NF-kappaB via two independent pathways in human renal
      tubular epithelial cells.
AB  - BACKGROUND: Endothelin-1 (ET-1) is a major transcriptional activator of renal
      proximal tubule cells acting in an autocrine and paracrine manner. In animal
      studies, ET-1 has been implicated in progressive renal interstitial fibrosis by
      promoting gene expression, possibly via the inflammatory NF-kappaB signal
      pathway. While ET-1-dependent mechanisms of signal transduction have been studied
      mainly in tumor cell lines, we analyzed the mechanism of ET-1-induced, NF-kappaB
      mediated target gene activation in proximal tubule cells. METHODS: Human renal
      proximal tubule cells were stimulated with ET-1 and gene expression analyzed by
      protein microarray, Western blot, non-radioactive electromobility shift assay,
      and quantitative real-time polymerase chain reaction. RESULTS: Activation of NF
      kappaB occurs only via an ET-1-specific type A receptor (not type B as in
      animals). Induction can be blocked by bosentan, and endothelin-A but not
      endothelin-B receptor-specific antagonists. Protein microarray screening shows
      activation of two independent cascades (via the endothelin-A receptor, or via
      diacylglycerol) leading to NF-kappaB induction. The independent induction is also
      reflected by target gene expression such as the vascular cell adhesion molecule
      1, interleukin-6, and fractalkine at different time points. CONCLUSION: Thus
      prohibiting ET-1-mediated gene transcription necessitates blocking of NF-kappaB
      and diacylglycerol signal transduction in proximal tubule cells.

PMID- 17460394
TI  - Prepare cells to repair the heart: mesenchymal stem cells for the treatment of
      heart failure.
AB  - Heart failure is one of the most important cardiovascular diseases, with high
      mortality, and invasive treatment such as mechanical circulatory support and
      cardiac transplantation is sometimes required for severe heart failure.
      Therefore, the development of less invasive and more effective therapeutic
      strategies is desired. Cell therapy is attracting growing interest as a new
      approach for the treatment of heart failure. As a cell source, various kinds of
      stem/progenitor cells such as bone marrow cells, endothelial progenitor cells,
      mesenchymal stem cells (MSC) and cardiac stem cells have been investigated for
      their efficacy and safety. Especially, bone marrow-derived MSC possess
      multipotency and can be easily expanded in culture, and are thus an attractive
      therapeutic tool for heart failure. Recent studies have revealed the underlying
      mechanisms of MSC in cardiac repair: MSC not only differentiate into specific
      cell types such as cardiomyocytes and vascular endothelial cells, but also
      secrete a variety of paracrine angiogenic and cytoprotective factors. It has also
      been suggested that endogenous MSC as well as exogenously transplanted MSC
      migrate and participate in cardiac repair. Based on these findings, several
      clinical trials have just been started to evaluate the safety and efficacy of MSC
      for the treatment of heart failure.

PMID- 17460395
TI  - Dialyzable uremic solutes contribute to enhanced oxidation of serum albumin in
      regular hemodialysis patients.
AB  - BACKGROUND: Oxidative stress (OS) is reportedly enhanced in patients receiving
      regular hemodialysis (HD). However, the in vivo redox state of HD patients,
      particularly after HD sessions, remains unclear. This study aimed to clarify the
      influence of HD on OS using the albumin redox state as a marker. METHOD: Blood
      samples of 8 regular HD patients were obtained during the course of study. The
      redox state of albumin was determined using high-performance liquid
      chromatography. RESULTS: The mean fraction of reversibly oxidized albumin [f(HNA
      1)] declined significantly over the course of the session and reached a minimum 4
      h after the session had ended (pre-HD, 36.16 +/- 7.50%; 4 h after HD, 25.71 +/-
      6.41%), then gradually rose to predialytic levels. The proportion of irreversibly
      oxidized albumin did not change significantly over time. Positive correlations
      were demonstrated between f(HNA-1) and uremic small solutes in each case.
      CONCLUSION: Accumulation of dialyzable uremic solutes may contribute to OS in HD
      patients.

PMID- 17460396
TI  - Rituximab (anti-CD20 monoclonal antibody)--ultimate or first choice in pemphigus?

PMID- 17460397
TI  - Sodium thiosulphate: a new way of treatment for calciphylaxis?
AB  - Sodium thiosulphate has been used in medicine for almost 100 years. There are
      some very important areas of application such as cyanide intoxications or the
      treatment of cisplatin toxicity. Till this day, this compound is almost unknown
      to most physicians. This is astonishing, especially because there are some
      promising reports in the literature describing a possibly wider area of
      application in different domains of medicine such as urology, nephrology or
      dermatology. Perhaps one of the most exciting and recent domains of sodium
      thiosulphate use is the treatment of calciphylaxis, providing new options dealing
      with this severe and mostly lethal illness. The goal of this article is to review
      the new application possibility of this compound.

PMID- 17460398
TI  - Increased number of cytotoxic CD3+ CD28- gammadelta T cells in peripheral blood
      of patients with cutaneous malignant melanoma.
AB  - BACKGROUND: A rise of CD3+ TCRgammadelta+ CD28- T cells has previously been
      observed after an in vitro long-lasting activation or even during viral
      infection. OBJECTIVE: The aim of this study was to investigate the expression of
      CD28 on lymphocytes bearing CD3/TCRgammadelta receptors in cancer, i.e. cutaneous
      melanoma. METHODS: TCRgammadelta lymphocytes were analysed in 41 Caucasian
      melanoma patients and 39 healthy individuals by flow cytometry. Patients were
      stratified according to the American Joint Committee on Cancer (AJCC) clinical
      stage. RESULTS: The number of circulating CD3+ TCRgammadelta+ T cells was
      significantly increased in both AJCC stages I-II and AJCC stage III patients
      compared with healthy individuals. This increase was mediated by an accumulation
      of the CD3+ TCRgammadelta+ CD28- T-cell subset, which expressed a high amount of
      perforin both in normal individuals and melanoma patients. CONCLUSION: This work
      shows, for the first time, a rise of the cytotoxic CD3+ TCRgammadelta+ CD28- T
      cell population in melanoma patients, which may be important in anticancer
      surveillance.

PMID- 17460399
TI  - Lack of association between exposure to topical calcineurin inhibitors and skin
      cancer in adults.
AB  - BACKGROUND: Two topical calcineurin inhibitors (TCI) are available for the
      treatment of atopic dermatitis and there has been concern that their use could be
      associated with an increased risk of nonmelanoma skin cancer (NMSC). OBJECTIVE:
      To determine if TCI exposure is associated with an increased risk of NMSC in
      adults. METHODS: A case-control study using a questionnaire mailed to 5,000
      adults with dermatitis. RESULTS: We received responses from 70.7% of those
      surveyed by mail. Overall, 25.7% reported exposure to TCI. TCI exposure was 14.4%
      for the cases and 30.7% for the controls. Our primary analysis was a comparison
      between those with NMSC and those without. The unadjusted odds ratio was 0.38
      (0.31-0.47) and the adjusted (age, gender, previous NMSC, history of atopic
      dermatitis) was 0.54 (0.41-0.69). The odds ratio of association for NMSC
      decreased as the number of tubes used and the potency of the agent increased.
      CONCLUSION: This early study shows that TCI use is not associated with an
      increased risk of NMSC in adults.

PMID- 17460400
TI  - Serum levels of the Th1 promoter IL-12 and the Th2 chemokine TARC are elevated in
      erythema multiforme and Stevens-Johnson syndrome/toxic epidermal necrolysis and
      correlate with soluble Fas ligand expression. An immunoenzymatic study from the
      Italian Group of Immunopathology.
AB  - BACKGROUND: No data exist as to Th2 chemokines in erythema multiforme (EM) and
      Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). OBJECTIVE: To
      evaluate thymus- and activation-regulated chemokine (TARC), macrophage-derived
      chemokine (MDC) and regulated upon activation, normal T-lymphocyte-expressed and
      secreted chemokine (RANTES) expression in EM and SJS/TEN and to correlate with
      the serum levels of the Th1 promoter interleukin (IL)-12 and soluble Fas ligand
      (sFasL). MATERIALS AND METHODS: IL-12, sFasL, TARC, MDC and RANTES expression
      were analyzed by ELISA techniques in 31 untreated EM (n = 24) or SJS/TEN (n = 7)
      patients and in 28 healthy donors (HD). RESULTS: EM and SJS/TEN exhibited
      significantly higher levels of TARC, IL-12 and sFasL with respect to HD. TARC
      upregulation paralleled both the IL-12 (p = 0.0225) and sFasL increase (p =
      0.0194). CONCLUSIONS: Our results support a role of TARC in the pathophysiology
      of EM/SJS/TEN and confirm the coexistence of a Th2 response in addition to the
      predominant Th1 profile.

PMID- 17460401
TI  - Are itch and chronic pain associated in adults? Results of a large population
      survey in Norway.
AB  - BACKGROUND: Few large-scale epidemiological studies have been performed on the
      prevalence of itch. Itch and pain are common and complex symptoms which
      contribute to the burden of disease. Although there is antagonistic interaction
      between itch and pain, there are also many similarities in their pathophysiology.
      OBJECTIVE: To investigate possible associations between chronic itch and chronic
      pain in a large population. METHODS: The design was cross-sectional. 18,770
      adults completed a self-administered questionnaire addressing sociodemographic
      factors, psychosocial factors and self-reported health including chronic itch and
      chronic pain. RESULTS: Individuals reporting pain and itch were more likely to be
      women (80 and 60%, respectively, compared to 55% in the total sample), had a
      lower income (49 and 37% compared to 32%), were more likely to be depressed (36
      and 20% compared to 11%) and reported poorer well-being (74 and 34% compared to
      25%). In an adjusted logistic regression, chronic pain was strongly associated
      with chronic itch (OR = 1.79, 95% CI = 1.43-2.24). CONCLUSION: This study
      demonstrates the association of chronic itch and chronic pain and points out the
      need of further studies that focus on both symptoms in dermatological diseases.

PMID- 17460402
TI  - Treatment of refractory pemphigus with the anti-CD20 monoclonal antibody
      (rituximab).
AB  - BACKGROUND: Pemphigus is a severe blistering disorder caused by autoantibodies to
      desmogleins 1 and 3. Because some patients with pemphigus never enter into
      remission, new immunosuppressants are warranted. Rituximab is a chimeric
      monoclonal antibody binding to the CD20 antigen on B cells, which proved to be
      effective in recalcitrant pemphigus. OBJECTIVES: To evaluate the efficacy and
      safety of rituximab in refractory pemphigus and to investigate its effects on the
      autoantibody profile. PATIENTS AND METHODS: Six patients with recalcitrant
      pemphigus were treated. Rituximab was administered intravenously at a dosage of
      375 mg/m2 body surface once weekly for 4 weeks. RESULTS: Three pemphigus
      foliaceus patients and 1 with mucocutaneous pemphigus vulgaris (PV) showed
      complete response over a follow-up period of up to 18 months. In one oral PV,
      control of the disease was achieved using pulse therapy with cyclophosphamide
      following rituximab withdrawal. In one PV with vegetating features, good
      improvement was obtained after 6 rituximab infusions. All patients tolerated the
      treatment well. Anti-desmoglein autoantibodies significantly decreased only in
      pemphigus foliaceus. CONCLUSIONS: This study highlights that rituximab is a
      valuable drug for refractory pemphigus, although the response of mucous membranes
      and cutaneous folds may be delayed.

PMID- 17460403
TI  - Successful use of vacuum-assisted closure therapy for leg ulcers caused by
      occluding vasculopathy and inflammatory vascular diseases--a case series.
AB  - BACKGROUND: Leg ulcers caused by vasculitis, small vessel occlusion or other rare
      conditions often prove to be very difficult to treat. Despite polypragmatic,
      systemic and localized therapy, many of these wounds are progressive and
      characterized by severe pain. METHODS AND RESULTS: We here portray the cases of 5
      patients with ulcers resistant to systemic therapy for the underlying disease,
      who were treated successfully using vacuum-assisted closure (VAC) for wound
      management. We present the advantages and disadvantages of this method, as well
      as illustrating the essential and known therapeutic principles. CONCLUSIONS: Our
      experience shows VAC to be an excellent and effective alternative in the
      treatment of therapy-resistant chronic wounds caused by vasculopathy (small
      vessel occlusion or vasculitis). We did not observe any pathergy or
      proinflammatory effects caused by VAC.

PMID- 17460404
TI  - Hidradenitis suppurativa and zinc: a new therapeutic approach. A pilot study.
AB  - BACKGROUND: Hidradenitis suppurativa (Verneuil's disease) is a chronic
      suppurative dermatosis involving apocrine glands with a severe impact on the
      quality of life, which is enhanced by the fact that the drugs usually prescribed
      are poorly effective. OBJECTIVE: We discuss a new therapeutic approach based on
      zinc salts. METHODS: We performed a pilot study on 22 patients, mainly from grade
      I or II in Hurley's classification. All included patients had previously been
      prescribed a treatment (antibiotic, isotretinoin, surgery or anti-androgens),
      which was inefficient. They were then treated with 90 mg of zinc gluconate per
      day (15 mg zinc per Rubozinc capsule). RESULTS: We observed a clinical response
      in all patients, with 8 complete remissions (CR) and 14 partial remissions (PR).
      When CR was obtained, the treatment was progressively decreased (average of 3.5
      capsules/day); 4/22 patients experienced side-effects, mainly gastro-intestinal.
      CONCLUSION: Zinc salts could provide a new therapeutic alternative for the
      treatment of hidradenitis suppurativa.

PMID- 17460405
TI  - Comparative effect of tacrolimus and betamethasone valerate on the passive
      sustainable hydration of the stratum corneum in atopic dermatitis.
AB  - BACKGROUND: There is ample evidence that the skin barrier function is altered in
      atopic dermatitis. Little information is available about the effect of topical
      corticosteroids and calcineurin inhibitors on this function. PURPOSE: To assess
      the water content and its rate of accumulation in the stratum corneum of atopic
      patients using an indirect electrometric method while on tacrolimus or
      betamethasone valerate treatment. METHOD: Twenty-one patients with moderate
      atopic dermatitis affecting both forearms completed this double-blind randomized
      study. One forearm was treated twice daily for 3 weeks with 0.1% tacrolimus
      ointment. The other forearm was similarly treated with 0.12% betamethasone
      valerate ointment. Electrometric measurements were made under continuous
      occlusion secured by a Nova Dermal Phase Meter sensor probe. Assessments were
      performed at inclusion, after the 3-week treatment and after a further 3-week
      follow-up out of treatment. RESULTS: During treatment, both compounds yielded a
      similar improvement in skin barrier function. Indeed, under probe occlusion, the
      rate of water accumulation was significantly decreased. This improvement was
      sustained after stopping the tacrolimus treatment. By contrast, the benefit was
      in part lost at the site that had been treated by betamethasone valerate.
      CONCLUSION: The difference in the effect of the 2 compounds may be due to the
      negative influence of betamethasone valerate on the epidermal metabolism leading
      to progressive atrophy of the tissue. The better preservation of the skin barrier
      function after stopping tacrolimus treatment may help retarding relapses of
      atopic dermatitis.

PMID- 17460406
TI  - Efficacy of 25% diluted fluticasone propionate 0.05% cream as wet-wrap treatment
      in cutaneous mastocytosis.
AB  - BACKGROUND: Mastocytosis is a disorder that can be subdivided into two forms:
      cutaneous and systemic. Patients with cutaneous mastocytosis only may suffer from
      cosmetic problems. Topical steroid application has been shown to be effective in
      cases of limited skin lesions. METHODS: A case-controlled pilot study was
      conducted during a 6-weeks treatment using diluted 25% fluticasone propionate
      0.05% cream under wet-wrap occlusion in 5 adults and 6 children. Improvement was
      measured up to the 24th week after treatment using the SCORMA Index. RESULTS: The
      results of this pilot study showed a partial but clear cosmetic improvement in 9
      of the 11 patients. The mean SCORMA Index decreased after treatment from 38 to
      26. CONCLUSION: 25% dilution of fluticasone propionate 0.05% cream under wet-wrap
      occlusion is an alternative treatment modality for alleviating the symptoms of
      cutaneous mastocytosis, but the improvement may be moderate and fall short of the
      patient's expectations.

PMID- 17460407
TI  - Unusual presentation of fibroma of tendon sheath.

PMID- 17460408
TI  - Photosensitivity might be associated with drug-induced hypersensitivity syndrome.

PMID- 17460410
TI  - William J. Cunliffe Scientific Awards. Advances in the study of stem-cell
      enriched hair follicle bulge cells: a review featuring characterization and
      isolation of human bulge cells.
AB  - Hair follicles repeatedly regress and reconstitute themselves, suggesting the
      presence of intrinsic tissue stem cells. Using label-retaining cell technique to
      detect slow-cycling stem cells, hair follicle stem cells were detected in the
      bulge region of the outer root sheath, which provides the insertion point for the
      arrector pili muscle and marks the bottom of the permanent portion of hair
      follicles. Later studies elucidated important stem cell characteristics of the
      bulge cells, including high proliferative capacity and multipotency to regenerate
      the pilosebaceous unit as well as epidermis. Isolation of living bulge cells is
      now feasible. In addition, microarray analyses revealed the global gene
      expression profile of the bulge cells. However, most of those studies were
      performed in mouse hair follicles and our understanding of human bulge cells has
      been limited. Recently, remarkable progress was made in human bulge cell biology.
      The morphologically ill-defined human bulge boundary was precisely determined by
      the distribution of label-retaining cells. Laser capture microdissection enabled
      accurate isolation of human bulge cells and control cell populations. Microarray
      comparison analyses between isolated bulge and nonbulge cells elucidated the
      molecular signature of human bulge cells and identified cell surface markers for
      living bulge cell isolation. Importantly, isolated living human bulge cells
      demonstrated stem cell characteristics in vitro. In this review, recent advances
      in hair follicle bulge cell research are summarized, especially focusing on the
      characterization and isolation of human bulge cells.

PMID- 17460411
TI  - William J. Cunliffe Scientific Awards. Characteristics and pathomechanisms of
      endogenously aged skin.
AB  - The skin, being in direct contact with several environmental factors (e.g. UV
      irradiation), does not only undergo endogenous aging, which has to do with the
      'biological clock' of the skin cells per se, but also exogenous aging. While
      exogenous skin aging has been extensively studied, the pathomechanisms of
      endogenous skin aging remain far less clear. Endogenous skin aging reflects
      reduction processes, which are common in internal organs. These processes include
      cellular senescence and decreased proliferative capacity, decrease in cellular
      DNA repair capacity and chromosomal abnormalities, loss of telomeres, point
      mutations of extranuclear mtDNA, oxidative stress and gene mutations. As a
      consequence, aged skin in nonexposed areas shows typical characteristics
      including fine wrinkles, dryness, sallowness and loss of elasticity. Recent data
      have illustrated that lack of hormones occurring with age may also contribute to
      the aging phenotype. Improvement of epidermal skin moisture, elasticity and skin
      thickness, enhanced production of surface lipids, reduction of wrinkle depth,
      restoration of collagen fibers and increase of the collagen III/I ratio have been
      reported after hormone replacement therapy or local estrogen treatment in
      postmenopausal women. Furthermore, an in vitro model of endogenous skin aging
      consisting of human SZ95 sebocytes which were incubated under a hormone
      substituted environment illustrated that hormones at age- and sex-specific levels
      were able to alter the development of cells by regulating their transcriptome. In
      conclusion, among other factors the hormone environment plays a distinct role in
      the generation of aged skin.

PMID- 17460412
TI  - Surgical treatment of early gastric cancer.
AB  - Around half the cases of gastric cancer are found in the early stage in Japan.
      With an expected good prognosis, many treatment options have been developed to
      maintain a good quality of life of the patients after the treatment. Gastric
      cancer is diagnosed with endoscopy, and the depth of invasion is diagnosed with
      endoscopy and endoscopic ultrasound. One of the new treatments is endoscopic
      submucosal dissection. Improvements in surgical treatment are minimizing lymph
      node dissection, reconstruction methods, laparoscopy-assisted surgery, and
      sentinel node navigation surgery. Minimizing lymph node dissection for early
      gastric cancer is well described in the Guidelines for Gastric Cancer Treatments.
      Pylorus-preserving gastrectomy, jejunal interposition, pouch reconstruction, and
      Roux-en-Y reconstruction after distal gastrectomy are improvements in
      reconstruction after gastrectomy. More and more surgeons start laparoscopy
      assisted gastrectomy with lymph node dissection. Even with these improvements,
      the 5-year survival of early gastric cancer is more than 90% in Japan. Further
      improvements would be possible in the future.

PMID- 17460413
TI  - Beta1 integrins mediate tubule formation induced by supernatants derived from
      KSHV-infected cells.
AB  - OBJECTIVE: Angiogenesis is defined as the formation of new blood vessels. In a
      recently concluded study, we identified Kaposi's sarcoma-associated herpesvirus
      (KSHV)-infected cells derived from primary effusion lymphoma (PEL) to overexpress
      vascular endothelial growth factor (VEGF) that had the propensity to mediate
      tubule formation on a Matrigel, an indicator of angiogenesis. The objective of
      this study was to determine the receptor molecules that mediate the tubule
      formation induced by the supernatant derived from KSHV-infected PEL cells.
      METHODS: The identity of receptor(s) that play a role in mediating tubule
      formation driven by PEL supernatant was determined by the classical in vitro
      angiogenesis assay conducted on a Matrigel. RESULTS: RGD peptides, antibodies,
      and siRNA specific to beta1 integrins significantly lowered the ability of the
      PEL supernatants to induce tubule formation by endothelial cells. beta1 Integrins
      mediated tubule formation to comparable levels in endothelial cells that were
      incubated with supernatants derived from uninduced or TPA-induced PEL cells.
      Interestingly, the beta1 integrins did not seem to have a major role in cellular
      attachment. CONCLUSION: We report for the first time a critical role for beta1
      integrins in angiogenesis supported by the supernatant from KSHV-infected PEL
      cells.

PMID- 17460414
TI  - Modulation of Epstein-Barr virus latent membrane protein 1 activity by
      intrabodies.
AB  - OBJECTIVE: The Epstein-Barr virus (EBV) has been implicated in the development of
      many human neoplasias including B lymphoma and nasopharyngeal carcinoma. EBV
      latent membrane protein 1 (LMP1) is essential to virus-induced B cell
      immortalization and the downregulation of cell adhesion molecules that increases
      cell motility. Therefore, identifying LMP1 activity modulation methods may lead
      to the development of new therapies for LMP1-positive tumors. METHODS: This study
      uses a phage display single-chain variable fragments (scFvs) library to screen
      recombinant antibodies specific to the LMP1 C terminal region. A total of 45
      individual clones were obtained, and these scFvs were cloned as intrabodies and
      transfected into LMP1-positive cells. RESULTS: One of the scFv clones, designated
      H3, was capable of reducing LMP1-mediated NF-kappaB activation in HEK293 cells.
      Immunofluorescence and co-immunoprecipitation studies show that scFv H3 could
      interact with LMP1 in vivo. In addition, expression of scFv H3 intrabody could
      reduce cell motility in MDCK-LMP1 cells in the transwell migration assay.
      CONCLUSION: These data indicate that scFv H3 intrabody can inhibit LMP1 functions
      in epithelial cells and may be useful for attenuating the LMP1 function in LMP1
      positive tumors.

PMID- 17460415
TI  - Chemotherapy for osteosarcoma without high-dose methotrexate: another piece in
      the puzzle.

PMID- 17460416
TI  - Chemotherapy for osteosarcoma without high-dose methotrexate: a 12-year follow-up
      on 53 patients.
AB  - BACKGROUND: The clinical relevance of polychemotherapy in osteosarcoma is
      undisputed and well proven. In this retrospective study we report the results of
      chemotherapy treatment without high-dose methotrexate (HDMTX) for osteosarcoma.
      PATIENTS AND METHODS: Between 1986 and 1992, 53 patients with stage IIB extremity
      osteosarcoma received multimodal therapy (age: 6-36 years, median 17 years). All
      patients received neoadjuvant and adjuvant chemotherapy with adriamycin,
      cisplatin, cyclophosphamide, and vincristine without HDMTX. In 60.4%, tumor
      volume was < or =150 ml and in 39.6% >150 ml. Surgical modalities were
      distributed as follows: 71.7% of patients received limb-sparing surgery, 20.8%
      ablative surgery, and 7.5% rotationplasty. 35.8% of patients developed pulmonary
      metastases. RESULTS: Overall survival (OAS) was 71.7% after 5 years and 67.2%
      after 10 years. Ten-year OAS was not observed with local recurrences; without
      local recurrence 10-year OAS was 74.2% (p = 0.002). Five-year OAS was 31.6% in
      patients who developed pulmonary metastases. Ten-year OAS was 71.1% and 61.1%
      when tumor volume was < or =150 ml and >150 ml, respectively (p = 0.445). Ten
      year OAS was 73.5% in responders to preoperative chemotherapy; in poor responders
      62.1% (p = 0.353). Event-free 10-year survival was 70.8% in responders and 48.3%
      in poor responders (p = 0.099). CONCLUSION: Compared to treatment protocols
      including HDMTX similar survival rates were achieved.

PMID- 17460417
TI  - Mitomycin C plus infusional 5-fluorouracil in platinum-refractory gastric
      adenocarcinoma: an extended multicenter phase II study.
AB  - OBJECTIVE: To assess the toxicity and activity of bolus mitomycin C (MMC) in
      combination with a 24-hour continuous infusion of 5-fluorouracil (5-FU) in
      gastric cancer patients who had received at least one prior chemotherapy regimen.
      PATIENTS AND METHODS: Patients were treated with MMC (10 mg/m(2)) on days 1 and
      22, 5-FU (2.6 g/m(2)) as a 24-hour infusion, and folinic acid 500 mg/m(2) weekly
      for 6 weeks. RESULTS: Thirty-four patients with gastric cancer, 16 after failure
      of first-line chemotherapy and 18 after failure of at least two prior
      chemotherapies, were included. In the intent-to-treat analysis, 9 (26.5%) of the
      34 patients had a partial response and 10 (29.4%) a disease stabilization
      (disease control rate 56%). The median time to progression was 3.3 months (CI95:
      2.8-3.7), and the median overall survival was 7.2 months (CI95: 5.9-8.4). Grade
      III/IV thrombocytopenia occurred in 14.7% of patients (n = 5), while the most
      frequent nonhematological grade III/IV toxicities were mucositis and diarrhea,
      each affecting 9% of patients. CONCLUSIONS: As the tested regimen was generally
      safe and well tolerated by the patients, MMC plus infusional 5-FU/folinic acid
      may be a potential second-line regimen for patients with advanced gastric cancer.

PMID- 17460418
TI  - Diagnostic value of ductoscopy in the diagnosis of nipple discharge and
      intraductal proliferations in comparison to standard methods.
AB  - BACKGROUND: Ductoscopy is gaining increased importance in the diagnosis of nipple
      discharge of unclear origin and intraductal proliferation. For this reason we
      compared its diagnostic value and feasibility to standard diagnostic methods.
      MATERIAL AND METHODS: Ductoscopy was compared to mammography, galactography,
      sonography, magnetic resonance imaging (MRI), nipple smear, fine needle
      aspiration cytology (FNAC), and high-speed core biopsy; feasibility, sensitivity,
      and specificity were investigated for each method. RESULTS: 71 ductoscopies were
      evaluated, which were followed up by open biopsies. Here, 3 invasive and 8 ductal
      carcinomas in situ were found, as well as 3 atypical ductal hyperplasias, 44
      papillomas/papillomatoses, and 13 benign findings. Feasibility of ductoscopy was
      in this series 100%. Duct sonography showed the highest sensitivity (67.3%),
      followed by MRI (65.2%), galactography (56.3%), ductoscopy (55.2%), and FNAC
      (51.9%). The highest specificity was shown by FNAC, core biopsy, and
      galactography (each 100.0%), followed by mammography (92.3%), nipple smear
      (77.8%), ductoscopy, and duct sonography (each 61.5%); the lowest specificity was
      displayed by MRI (25.0%). CONCLUSION: The results confirm that ductoscopy can be
      performed within the same range of sensitivity and specificity as other
      techniques. In order to make conclusive statements about ductoscopy, especially
      in order to precisely define the indications for this method, a prospective
      multicenter study was initiated.

PMID- 17460419
TI  - Penile metastasis from a T1b prostate carcinoma.
AB  - BACKGROUND: Penile metastasis from incidental prostate carcinoma has not been
      described to date. CASE REPORT: The case of a 72-year-old man affected by penile
      metastasis from incidental prostate carcinoma is described. In March 1998, the
      patient underwent prostate surgery for lower urinary tract symptoms related to
      benign prostatic obstruction. Histological examination revealed an incidental
      adenocarcinoma of the prostate. The pre-operative prostate-specific antigen (PSA)
      value was 3.6 ng/ml. A prostate biopsy in the peripheral prostate lobes was
      negative. PSA progressively rose to 8 ng/ml. The prostate biopsy was repeated and
      was still negative. The patient was subjected to radiotherapy, as a result of
      which his PSA fell to 0.7 ng/ml. 4 years after prostatectomy, the PSA rose again
      and the patient underwent hormonal therapy. The PSA fell to < 0.001 ng/ml. In May
      2004, the patient reported a painful, erythematous nodule on his penis glans.
      Surgical biopsy showed a metastasis from prostate adenocarcinoma and he underwent
      partial penectomy. Due to disease progression, the patient underwent medical
      therapy. PSA and testosterone were always at minimum levels. 20 months later the
      patient died. CONCLUSION: We underline the uncertainty of the biological
      behaviour and optimal management of incidentally identified prostate carcinoma.
      In addition, we highlight that biological and clinical progression could be the
      consequence of inadequate treatment recommendations.

PMID- 17460420
TI  - Atrial fibrillation induced by gemcitabine treatment in a 65-year-old man.
AB  - BACKGROUND: Gemcitabine, a pyrimidine analogue, is a cell cycle-specific
      antineoplastic agent that is structurally related to cytarabine. Major side
      effects of the treatment with gemcitabine are hepatic dysfunction,
      myelosuppression, renal impairment and pulmonary toxicity. Development of atrial
      fibrillation (AF) during gemcitabine treatment is very rare and was reported in
      only 2 case reports in the literature. CASE REPORT: We report the case of a 65
      year-old man who developed AF under gemcitabine therapy for non-small cell lung
      cancer (stage IIIB). In this patient, AF was intrinsically associated with
      chemotherapy administration which triggered arrhythmia. CONCLUSION: Although AF
      caused by gemcitabine appears to be rare, patients at risk of developing atrial
      fibrillation should be closely monitored for this complication.

PMID- 17460421
TI  - Multiple littoral cell angioma of the spleen: a case report and review of the
      literature.
AB  - BACKGROUND: Littoral cell angioma (LCA) is a rare benign vascular tumor of the
      spleen with characteristic histomorphologic features. It is a unique splenic
      tumor which may present with abdominal pain or as an incidental finding. CASE
      REPORT: In this case report, we present the case of a 34-year-old woman with
      multiple splenic LCA. Initially, the patient presented with abdominal pain,
      weakness and fatigue. After a diagnostic abdominal ultrasound, multiple
      hemangiomas were observed in the spleen. Computed tomography scans confirmed
      splenomegaly with multiple round and hyperdense lesions. The patient subsequently
      underwent splenectomy. Postoperative histological and immunohistochemical
      profiles confirmed the diagnosis of LCA. CONCLUSION: LCA is a unique splenic
      tumor diagnosed in patients with abdominal pain or as an incidental finding. Only
      a few case reports of this tumor have been published, and those accounts are
      inconsistent. In the present paper, we report on a case and conduct a literature
      review.

PMID- 17460422
TI  - Do the results of the new trials change the standard treatment of metastatic
      renal cell cancer?
AB  - With the emergence of novel angiogenesis inhibitors, we are moving to a new era
      for patients with metastasized renal cell carcinoma. Since the results achieved
      reflect more a modification of the natural course of the disease than a cure,
      past achievements should not be neglected. Low-risk patients with clear cell
      histology, especially those with pulmonary metastasis only, should still be
      offered cytokine therapy. For intermediate-risk patients sunitinib is the
      treatment of choice. For high-risk patients, temsirolimus has to date provided
      the most convincing data, its availability is however limited. Data with
      sorafenib and sunitinib in the high-risk group are still anecdotal. The toxicity
      profiles of these 2 drugs are different and might particularly relate to patients
      with known cardiovascular co-morbidity. No sufficient data are available
      regarding sequential use. After cytokine failure, sorafinib is the treatment of
      choice. Patients should preferably be treated within clinical trials to answer
      unaddressed questions. It is well known that the strict entry criteria used
      within the clinical studies were applied very flexibly when drugs have been
      approved. These aspects require a careful follow-up to ascertain optimal use and
      to prevent misuse. Finally, the costs of prolonged treatment will be enormous,
      and only meaningful survival advantages will convince the health authorities to
      make these new treatments available for all patients.

PMID- 17460423
TI  - Report on the 1st international workshop of the german competence network
      malignant lymphomas.
AB  - The German Competence Network Malignant Lymphomas (KML) is an initiative of the
      German Federal Ministry of Education and Research with the goal of establishing a
      cooperative network between lymphoma study groups to support clinical lymphoma
      research. The network was initiated in 1999 and comprises 9 national lymphoma
      study groups. More than 8,600 patients are recruited every year into currently 55
      clinical trials by more than 2,400 centers in Germany and Europe. It was the
      specific aim of the 1st international workshop of the KML (March 6 and 7, 2006)
      in Cologne to bring together international specialists in the field of lymphoma
      to discuss current concepts of lymphoma pathogenesis and treatment strategies.
      This report summarizes novel aspects of pathogenesis and targeted approaches,
      maintenance therapy, management of the elderly patients, and the use of positron
      emission tomography for clinical decision making.

PMID- 17460424
TI  - Comparison of surgically induced astigmatisms after clear corneal incisions of
      different sizes.
AB  - PURPOSE: This study was performed to assess efficiency and stability of
      astigmatic change by incision size after cataract surgery. METHODS: This work was
      designed as a retrospective, comparative, nonrandomized interventional study. A
      total of 121 cases of cataract surgery were reviewed in 98 patients performed by
      one surgeon at the Oregon Eye Institute in Eugene, OR, USA with 3-year follow
      ups. All procedures were performed with the temporal approach of self-sealing
      incisions. The serial change in surgically induced astigmatisms were examined in
      all cases of three groups: Group A, cartridge injection of a foldable IOL through
      a 2.5 mm self-sealing incision; Group B, cartridge injection of a foldable IOL
      through a 3.0 mm self-sealing incision; Group C, cartridge injection of a
      foldable IOL through a 3.5 mm self-sealing incision. Keratometric data were
      obtained preoperatively, and 3 weeks, 3 months, 6 months, 9 months, 12 months, 24
      months and 36 months postoperatively. Polar value analysis was performed to
      calculate the surgically induced astigmatism. RESULTS: The astigmatic change
      decreased over time in Group B (P<0.05). The other groups tended to remain in
      induced astigmatism. All groups showed anticlockwise torque at 3 weeks following
      surgery. Group B showed a decrease in deviation, but the other groups showed
      increases in their torque value at postoperative 12 months (P<0.05). CONCLUSIONS:
      The 3.0 mm incision size correlated with the least surgically induced
      astigmatism.

PMID- 17460425
TI  - The effect of diffuse lamellar keratitis on visual acuity and contrast
      sensitivity following LASIK.
AB  - PURPOSE: To evaluate visual outcome and the changes of contrast sensitivity (CS)
      after diffuse lamellar keratitis (DLK). METHODS: Using retrospective chart
      review, 48 eyes of 25 patients who underwent laser in situ keratomileusis (LASIK)
      with Visx S4 (VISX Inc., Santa Clara, CA) and M2 (Moria, France) and who were
      followed for at least six months were included. They were divided into two
      groups: DLK and non-DLK, by diagnosis of DLK or its absence after LASIK.
      Postoperative logMAR visual acuities and logCS measured using the VCTS 6500
      (Vistech Consultants, Inc., Dayton, OH) were compared with preoperative values in
      the DLK and non-DLK groups at three and six months after LASIK. RESULTS: There
      was no difference in logMAR visual acuity between the DLK and non-DLK groups
      until the sixth postoperative month. However, CS was significantly decreased at
      12 and 18 cycle/degree compared with preoperative values (p=0.043 and p=0.045,
      respectively) in the DLK group, whereas CS was significantly increased at 12
      cycle/degree in the non-DLK group (p=0.042) at six months. CONCLUSIONS: DLK
      seemed to be strongly associated with a postoperative decrease of CS.

PMID- 17460426
TI  - Laser photocoagulation combined with intravitreal triamcinolone acetonide
      injection in proliferative diabetic retinopathy with macular edema.
AB  - PURPOSE: To evaluate therapeutic effects and usefulness of a combination
      treatment of intravitreal injection of triamcinolone acetonide (IVTA) and
      panretinal photocoagulation (PRP) in patients with clinically significant macular
      edema secondary to proliferative diabetic retinopathy (PDR). METHODS: Visual
      acuity test, fundoscopy, fluorescein angiography, and optical coherence
      tomography (OCT) were taken in 20 patients (20 eyes) of macular edema and PDR. A
      combination of intravitreal injection of triamcinolone acetonide and PRP was
      performed in 10 patients (10 eyes) and a combination of focal or grid laser
      photocoaqulation and PRP in the remaining 10 eyes. The postoperative outcomes
      were compared between the two combination treatments by best corrected visual
      acuity (BCVA), tonometry, fluorescein angiography, and OCT at 2 weeks, 1, 2, and
      3 months. RESULTS: Average BCVA (log MAR) significantly improved from
      preoperative 0.56-/+0.20 to 0.43-/+0.08 at 1 month (P=0.042) and it was
      maintained until 3 months after a combination of IVTA and PRP in 10 eyes
      (P=0.007). The thickness of fovea decreased from average 433.3-/+114.9 micrometer
      to average 279.5-/+34.1 micrometer at 2 weeks after combined treatment of IVTA
      and PRP (P=0.005), which was significantly maintained until 3 months, but there
      was a transient visual disturbance and no significant difference in thickness of
      the fovea before and after treatment in the groups with PRP and focal or grid
      laser photocoagulation. CONCLUSIONS: A combination of IVTA and PRP might be an
      effective treatment modality in the treatment of macular edema and PDR and
      prevent the subsequent PRP-induced macular edema result in visual dysfunction. In
      combination with PRP, IVTA might be more effective than focal or grid laser
      photocoagulation and PRP for reducing diabetic macular edema and preventing
      aggravation of macular edema without transient visual disturbance in patients
      requiring immediate PRP.

PMID- 17460427
TI  - Early versus late intravitreal triamcinolone acetonide for macular edema
      associated with branch retinal vein occlusion.
AB  - PURPOSE: To compare the effect of early versus late intravitreal injection of
      triamcinolone in patients with macular edema due to branch retinal vein occlusion
      (BRVO). METHODS: Twenty eyes of 20 patients with macular edema from BRVO,
      including 10 with duration after onset of or <or= 3 months and 10 with duration
      of 3 months, were treated using a single intravitreal triamcinolone injection (4
      mg/0.1 ml). Best-corrected visual acuity and foveal thickness by optical
      coherence tomography were measured 1, 3, and 6 months post-injection. RESULTS: In
      patients that received treatment after a disease duration of <or= 3 months,
      visual acuity and foveal thickness significantly improved from baseline over 6
      months of follow-up. However, in those with a duration of >3 months, improvements
      in visual acuity and foveal thickness, though apparent at 1 month, were not
      maintained at 3 and 6 months post-triamcinolone. CONCLUSIONS: Intravitreal
      triamcinolone is more effective in patients with BRVO who are treated earlier.

PMID- 17460428
TI  - Direct detection of reactive nitrogen species in experimental autoimmune uveitis.
AB  - PURPOSE: Demonstrate unequivocally the generation of nitric oxide in experimental
      autoimmune uveoretinitis by electron spin resonance spectroscopy (ESR) using
      ferrous iron complex of N-methyl-D-glucamine dithiocarbamate, (MGD)(2)-Fe(2+), as
      a spin trap. METHODS: Experimental autoimmune uveitis was induced in Lewis rats,
      and at the peak of the intraocular inflammation, the animals received
      intravitreous injections of the spin trap. The retina and choroid dissected from
      the enucleated globes were subjected to ESR. Similarly, the retina and choroid
      obtained at the peak of experimental autoimmune uveo-retinitis (EAU) were placed
      in a vial containing luminal, and chemiluminescence was counted on a Packard
      liquid scintillation analyzer. RESULTS: The ESR three-line spectrum (g=2.04;
      a(N)=12.5 G) obtained was characteristic of the adduct [(MGD)(2)-Fe(2+)-NO]. The
      majority of this signal was eliminated by the inducible nitric oxide synthase
      (iNOS) specific inhibitor aminoguanidine injected inflamed retina was detected
      when compared with that of the non inflamed controls. The chemiluminescent
      activity was further increased two-fold by the addition of bicarbonate to the
      inflamed retina; the phenomenon is attributable only to the presence of a high
      steady-state concentration of peroxynitrite. CONCLUSIONS: The study shows an
      unequivocal presence of nitric oxide in EAU retina and choroid and the generation
      of peroxynitrite. High levels of these reactive nitrogen species generated in the
      inflamed retina and choroids are certain to cause irreversible tissue damage,
      especially at the susceptible sites such as photoreceptors.

PMID- 17460429
TI  - The therapeutic effects of angiotensin-converting enzyme inhibitors in severe non
      proliferative diabetic retinopathy.
AB  - PURPOSE: To evaluate the effects of angiotensin-converting enzyme inhibitors (ACE
      I) in retarding progression of severe non-proliferative diabetic retinopathy
      (NPDR) in normotensive type 2 diabetic patients. METHODS: This was a
      retrospective case control study of 128 patients with normotensive type 2
      diabetes with lower than +1 dipstick proteinuria and severe NPDR who were
      classified into either an ACE-I treated group (Enalapril maleate 10 mg, n=12 ,
      Ramipril 5 mg, n=17) or an ACE-I untreated group (n=99). Medical records were
      reviewed for endpoints of (a) occurrence of proliferative diabetic retinopathy
      (PDR) or macular edema (ME) for which laser phototherapy was necessary or (b)
      development of proteinuria of higher than +1 level requiring medication of ACE-I.
      RESULTS: From the total of 128 patients, there were 29 ACE-I treated patients and
      99 ACE-I untreated patients. There were no differences in the average age,
      duration of diabetes, body mass indices, blood pressure and levels of
      hyperglycemia or HbA1C between the two groups. Blood pressure and HbA1C levels in
      both groups remained unchanged during the study. The mean follow-up period was
      41.6 months. In the ACE-I group, 6 patients progressed to PDR, 5 to ME and 6
      developed proteinuria of greater than +1 over the follow-up period. In the
      control group, 30 patients progressed to PDR, 6 to ME and 9 developed proteinuria
      of greater than +1 over the follow-up period. CONCLUSIONS: Small doses of ACE-I
      did not yield any beneficial effects in retarding the progression of severe NPDR.

PMID- 17460430
TI  - Investigation of the association between normal-tension glaucoma and single
      nucleotide polymorphisms in natriuretic peptide gene.
AB  - PURPOSE: The expression of natriuretic peptides in the neural bundles of the
      anterior portion of the optic nerves and their functions in regulating vessel
      tone and blood flow may suggest a possible role in the pathogenesis of glaucoma.
      The purpose of this study was to investigate the association between normal
      tension glaucoma and the genetic variations of atrial natriuretic peptide (Nppa)
      and natriuretic peptide receptor A (Npr1) gene. METHODS: Sixty-seven Korean
      normal-tension glaucoma (NTG) patients and 100 healthy subjects (as normal
      controls) were enrolled. DNA from peripheral blood leukocytes was extracted, and
      the genotypes of five polymorphisms (c.94G>A, c.454T>C, IVS1+16C>T, IVS2+701G>A,
      and c.-764C>G) in the Nppa gene and one polymorphism (c.1023G>C) in the Npr1 gene
      were determined using the restriction fragment length polymorphism and the
      SNaPshot methods. The genotype and allele frequencies of these polymorphisms in
      patients with NTG and normal controls were compared using the Fisher's exact test
      and the chi-square test. RESULTS: In both groups, the genotype distributions were
      in accordance with the Hardy-Weinberg equilibrium. There was no significant
      difference in the frequency of the Nppa and Npr1 alleles or genotypes in the
      normal-tension glaucoma group as compared to the control group. CONCLUSIONS: Nppa
      and Npr1 gene polymorphisms are not associated with normal-tension glaucoma,
      suggesting that this gene does not have an important role in the pathogenesis of
      optic neuropathy in this disease.

PMID- 17460431
TI  - Insulin enhances nitric oxide production in trabecular meshwork cells via de novo
      pathway for tetrahydrobiopterin synthesis.
AB  - PURPOSE: To investigate the effect of insulin on the production of nitric oxide
      (NO) in the trabecular meshwork (TM) cells and the enzymatic synthetic pathway of
      tetrahydrobiopterin (BH(4)) synthesis. METHODS: Primarily cultured human TM cells
      were exposed to 1, 10, and 100 microgram/ml of insulin and 0, 1, 10, 100 and 1000
      nM dexamethasone for 3 days. To evaluate the enzymatic pathway of BH(4)
      synthesis, 10 microM dexamethasone, 5 mM diaminopyrimidinone, 100 microM ascorbic
      acid, 100 microM sepiapterin, or 10 microM methotrexate were also co-administered
      respectively. Cellular survival and NO production were measured with MTT and
      Griess assay. RESULTS: Insulin enhanced NO production in a dose-dependent manner
      significantly (0.05) without affecting cell viability, whereas dexamethasone
      inhibited NO production. With co-exposure of insulin, diaminopyrimidinone and
      sepiapterin inhibited insulin-induced NO production. Ascorbic acid increased NO
      production independent of insulin and methotrexate did not affect to the action
      of insulin in NO production. CONCLUSIONS: Insulin increases NO production in TM
      cells via de novo synthetic pathway for BH(4) synthesis. Insulin could be
      involved in the regulation of trabecular outflow by enhancing NO production in TM
      cells.

PMID- 17460432
TI  - Endogenous aeromonas hydrophila endophthalmitis in an immunocompromised patient.
AB  - PURPOSE: To report a case of endogenous endophthalmitis due to Aeromonas
      hydrophila in a patient with distal common bile duct carcinoma and biliary
      sepsis. METHODS: A 72-year-old woman with distal common bile duct carcinoma,
      obstructive jaundice, diabetes mellitus, and hypertension had a 1-day history of
      blurred vision, redness, and eye discharges in the right eye. An ophthalmic
      examination showed no light perception vision, increased intraocular pressure,
      severe corneal edema, severe anterior chamber reaction, exudative membranes on
      the anterior lens surface, and severe vitreal reaction. There was no ocular
      history of trauma, infection, or surgery in either eye. RESULTS: Under the
      impression of endogenous bacterial endophthalmitis, immediate intraocular
      cultures and intravitreal antibiotic injections were performed, but the anterior
      chamber reaction, and the ultrasonogram findings were deteriorated. Evisceration
      was undertaken because of extrusion of the intraocular contents, and Aeromonas
      hydrophila was isolated by intraocular culture. CONCLUSIONS: Endogenous
      endophthalmitis due to Aeromonas hydrophila is rare, but has a rapid clinical
      course and a poor prognosis, despite of prompt diagnosis and management.

PMID- 17460433
TI  - A case of oular sparganosis in Korea.
AB  - PURPOSE: To present a case of ocular sparoganosis presenting as itching
      sensation. METHODS: A 60-year-old woman presented for removal of an itchy
      subconjunctival mass in her left eye. Her ocular findings were normal, except for
      a subconjunctival mass (1.5 x 1.5 mm). RESULTS: A parasite excised from the
      subconjunctival mass was identified as a sparganum, by microscopic examination
      after hematoxylin-eosin staining. The mummified parasite was identified as the
      plerocercoid phase of the sparganum, by microscopy. CONCLUSIONS: Although rare,
      parasitic disease should be suspected in a palpable subconjunctival mass
      unresponsive to the medical treatment.

PMID- 17460434
TI  - Progressive outer retinal necrosis combined with vitreous hemorrhage in a patient
      with acquired immunodeficiency syndrome.
AB  - PURPOSE: To describe an unusual case of rapidly progressive outer retinal
      necrosis (PORN) with vitreous hemorrhage in a 41-year-old woman with acquired
      immunodeficiency syndrome (AIDS), who had retinitis developed from what was
      probably varicellar-zoster virus combined with cytomegalovirus (CMV) and herpes
      simplex type 1,2, as proven by the polymerase chain reaction restriction fragment
      length polymorphism method (PCR-RFLP). METHODS: This study is a case report
      detailing clinical follow-up and an aqueous humor test by PCR-RFLP. RESULTS: The
      deep, white retinal lesions coalesced and progressively expanded in a
      circumferential manner, with sparing of the perivascular retina. However, retinal
      and vitreous hemorrhages, unusual findings for PORN, could be noted around the
      optic nerve. Varicellar-zoster virus (VZV), cytomegalovirus (CMV), and herpes
      simplex types 1,2 (HSV-1,2) were detected in the aqueous humor by PCR.
      CONCLUSIONS: PORN has been described as a variant of necrotizing herpetic
      retinopathy, occurring particularly in patients with AIDS. Although the etiologic
      agent has been reported to be VZV, concurrent or combined etiologic agents can
      include HSV-1, HSV-2, and CMV in AIDS patients. Therefore, combined antiviral
      therapy with acyclovir and ganciclovir could be more reasonable as an initial
      therapy.

PMID- 17460435
TI  - Therapeutic effect of diode laser photodynamic therapy with ICG dye in ARMD: a
      case report.
AB  - PURPOSE: To evaluate the diode laser photodynamic therapy efficacy on choroidal
      neovascularization (CNV) in the treatment of three patients with age-related
      macular degeneration (ARMD). METHODS: The authors selected three patients with
      ARMD whose vision has decreased due to CNV, and applied diode laser treatment
      after injecting an indocyanine green (ICG) solution. The patients were followed
      for at least three months after treatment, and examinations included evaluating
      vision changes and possible leakage on fluorescein angiography (FAG). RESULTS:
      The final vision of two patients improved by more than one line on the Early
      Treatment Diabetic Retinopathy Study (ETDRS) chart after at least three months of
      follow-up. However, the final vision of the third patient decreased by one line
      on ETDRS chart. FAG was done in all patients, and in two of the patients, there
      was no evidence of leakage at the laser-applied site. In the other patient, there
      was evidence of minimal leakage, with the area of leakage decreasing by more than
      fifty percent. Side effects of ICG were not found during or after the
      photodynamic therapy sessions. CONCLUSIONS: The photodynamic usage of ICG
      treatment of CNV in patients with ARMD, was effective in preventing or improving
      the visual outcome. Compared to the widely used verteporfin, ICG is more stable
      and is more cost effective. The authors therefore came to a conclusion that ICG
      can be very useful in the treatment of CNV. However, further studies are
      necessary.

PMID- 17460436
TI  - Acute angle-closure glaucoma from spontaneous massive hemorrhagic retinal
      detachment.
AB  - PURPOSE: To report a case of acute angle-closure glaucoma resulting from
      spontaneous hemorrhagic retinal detachment. METHODS: An 81-year-old woman visited
      our emergency room for severe ocular pain and vision loss in her left eye. Her
      intraocular pressures (IOPs) were 14 mmHg in the right eye and 58 mmHg in the
      left eye. Her visual acuity was 0.4 in the right eye but she had no light
      perception in the left eye. The left anterior chamber depth was shallow and
      gonioscopy of the left eye showed a closed angle. In comparison, the right
      anterior chamber depth was normal and showed a wide, open angle. Computed
      tomography and ultrasonography demonstrated retinal detachment due to subretinal
      hemorrhage. After systemic and topical antiglaucoma medications failed to relieve
      her intractable severe ocular pain, she underwent enucleation. RESULTS: The
      ocular pathology specimen showed that a large subretinal hemorrhage caused
      retinal detachment and pushed displaced the lens-iris diaphragm, resulting in
      secondary angle-closure glaucoma. CONCLUSIONS: Prolonged anticoagulant therapy
      may cause hemorrhagic retinal detachment and secondary angle-closure glaucoma. If
      medical therapy fails to relieve pain or if there is suspicion of an intraocular
      tumor, enucleation should be considered as a therapeutic option.

PMID- 17460437
TI  - A proposal concept of a polygene network in systemic vasculitis: lessons from MRL
      mouse models.
AB  - In addition to the studies of cellular and molecular events in the pathogenesis
      of systemic vasculitis, a genome analysis of mouse models may shed some light on
      the complex clinicopathological manifestations of systemic vasculitis. In the
      study of susceptibility loci to vasculitis in MRL mouse models, we learned that
      systemic vasculitis developed in a cumulative effect of multiple gene loci, each
      of which by itself did not have a significant effect to induce the related
      phenotype, thus indicating a polygenic system. The mice developed vasculitis in
      an additive manner of multiple genes with a hierarchical effect. Some of the
      susceptibility loci seemed to be common to those in other collagen diseases as
      well. Moreover, the loci controlling tissue specificity of vasculitis were
      present. One of the positional candidate genes for vasculitis showed an allelic
      polymorphism in the coding region, thus possibly causing a qualitative difference
      in its function. As a result, a particular combination of polygenes with such an
      allelic polymorphism may thus play a critical role in leading the cascade
      reaction to develop vasculitis, and also a regular variation of systemic
      vasculitis. This is designated as the polygene network in systemic vasculitis.

PMID- 17460438
TI  - ANCA-associated vasculitis: diagnostic and therapeutic strategy.
AB  - Among small-vessel vasculitides, microscopic polyangiitis (MPA), Wegener's
      granulomatosis (WG), and allergic granulomatous angiitis (AGA) are known
      collectively as ANCA-associated vasculitis (AAV) because of the involvement of
      anti-neutrophil cytoplasmic antibodies (ANCA) as the common pathogenesis. Major
      target antigens of ANCA associated with vasculitis are myeloperoxidase (MPO) and
      proteinase 3 (PR3). MPO-ANCA is related to MPA and AGA, and PR3-ANCA is the
      marker antibody in WG. MPO-ANCA-associated vasculitis is more frequent in Japan,
      whereas PR3-ANCA-associated vasculitis is more common in Europe and USA. ANCA
      appears to induce vasculitis by directly activating neutrophils. Therefore, no
      immunoglobulins or complement components are detected in the vasculitis lesions;
      hence, AAV is called pauci-immune vasculitis (pauci = few/little). Untreated
      patients with severe AAV with multi-organ involvement have a poor prognosis,
      which is improved by combination therapy with cyclophosphamide and high-dose
      corticosteroid. Randomized controlled trials (RCT) regarding induction and
      maintenance of remission of AAV indicated that the rate of remission induction by
      the standard regimen is approximately 90% in 6 months, that maintenance of
      remission can be achieved with oral azathioprine as well as cyclophosphamide, and
      that methotrexate can be used only for non-renal mild AAV. As these data were
      obtained mostly in patients positive for PR3-ANCA, caution must be taken in
      applying these findings to Japanese patients, most of whom are positive for MPO
      ANCA. A prospective study is now underway to clarify the effectiveness of the
      standard regimen in Japanese patients with MPO-ANCA-associated vasculitis. This
      article describes the diagnostic criteria and the recent evidence-based
      therapeutic strategy of AAV.

PMID- 17460439
TI  - Treatment for Churg-Strauss syndrome: induction of remission and efficacy of
      intravenous immunoglobulin therapy.
AB  - Churg-Strauss syndrome (CSS) is characterized by the presence of asthma,
      eosinophilia, and small-vessel vasculitis with granuloma. It is a distinct
      entity, as determined from all classifications of systemic vasculitis. The poor
      prognostic factors in CSS are renal insufficiency, cardiomyopathy, severe
      gastrointestinal (GI) tract, and central nervous systems (CNS) involvement. The
      initial management of CSS should include a high dose of a corticosteroid:
      prednisone at 1 mg/kg/day or its equivalent for methylprednisolone with tapering
      over 6 months. In patients with severe or rapidly progressing CSS, the
      administration of methylprednisolone pulse at 1 g/body/day for 3 days is
      recommended. When corticosteroid therapy does not induce remission, or when
      patients have poor prognostic factors, immunosuppressive cytotoxic therapy is
      indicated. However, some patients with severe CSS often show resistance to
      conventional treatment. We think that IVIG therapy is a hopeful candidate for
      second-line treatment for CSS patients, particularly in the case of neuropathy
      and/or cardiomyopathy, which are resistant to conventional therapy. However,
      there is not much evidence supporting the effectiveness of IVIG in CSS, and the
      mechanisms underlying the action of IVIG remain unclear. Now we are performing
      clinical trials of IVIG therapy for CSS patients who are resistant to
      conventional treatment, through a nationwide double-blinded placebo-controlled
      study in Japan.

PMID- 17460440
TI  - Therapeutic strategies for systemic necrotizing vasculitides.
AB  - Treatments of vasculitides have progressed markedly over the past few decades.
      The first attempts to obtain better-adapted therapeutic strategies evaluated the
      indications of conventional drugs, and their abilities prolong survival and
      reduce the number of relapses, while decreasing the severity and number of side
      effects. Many prospective clinical trials were organized by the French Vasculitis
      Study Group and the European Vasculitis Study group, and have contributed to
      optimizing targeted treatment strategies. Recent therapeutic strategies include
      immunomodulating methods, like plasma exchanges, or products, like intravenous
      immunoglobulins, or, more recently, new agents called biotherapies. Some of them
      have achieved promising positive effects, for example, anti-CD20 monoclonal
      antibodies, and are now being evaluated in prospective trials.

PMID- 17460441
TI  - A novel atopic dermatitis model induced by topical application with
      dermatophagoides farinae extract in NC/Nga mice.
AB  - BACKGROUND: Atopic dermatitis is a chronically relapsing inflammatory skin
      disease. Animal models induced by relevant allergens play a very important role
      in the elucidation of the disease. The patients with atopic dermatitis are highly
      sensitized with mite allergens such as Dermatophagoides farinae (Df). Therefore,
      in the present study, we tried to develop a novel model for atopic dermatitis by
      repeated application with Df extract ointment. METHODS: Df extract ointment was
      repeatedly applied to the back of NC/Nga mice together with barrier disruption.
      Atopic dermatitis-like skin lesions were evaluated by dermatitis scores, skin
      histology and immunological parameters. The effect of corticosteroid and
      calcineurin inhibitor was also examined. RESULTS: Repeated application of Df
      extract ointment caused rapid increase in dermatitis scores. Clinical (skin
      dryness, erythema, edema and erosion) and histological symptoms (dermal and
      epidermal thickening, hyperkeratosis, parakeratosis and inflammatory cell
      infiltration) in this model were very similar to those in human atopic
      dermatitis. Serum total and Df-specific IgE levels were elevated in this model
      compared with normal mice, and draining lymph node cells isolated from the mice
      that exhibited dermatitis produced significant amounts of interleukin-5,
      interleukin-13 and interferon-gamma after re-stimulation with Df. Furthermore,
      current first-line drugs for the treatment of human atopic dermatitis,
      corticosteroid and tacrolimus ointments, were effective against the clinical and
      histological symptoms in this model. CONCLUSIONS: These results suggest that the
      model we have established is useful for not only elucidating the pathogenesis of
      atopic dermatitis but also for evaluating therapeutic agents.

PMID- 17460442
TI  - Allergen-specific T-cell response in patients with phenytoin hypersensitivity;
      simultaneous analysis of proliferation and cytokine production by
      carboxyfluorescein succinimidyl ester (CFSE) dilution assay.
AB  - BACKGROUND: Phenytoin can induce diversified adverse reactions including
      generalized eruptions and the hypersensitivity syndrome. Delayed-type allergic
      mechanisms have been postulated to underlie these reactions. The tests most
      widely used to detect T-cell sensitization to drugs are the patch test and the
      lymphocyte transformation test (LTT), but their sensitivity is not sufficient.
      Simultaneous assessment of both the frequencies and the cytokine-producing
      phenotypes of allergen-specific T cells has become possible with the recently
      introduced carboxyfluorescein succinimidyl ester (CFSE) assay. METHODS: Seven
      patients who presented with phenytoin-induced maculopapular exanthema with and
      without fever were included in this study. Peripheral blood mononuclear cells
      (PBMCs) were labeled with CFSE and cultured with phenytoin for seven days. The
      cells were stained with anti-CD4 and cytokine-specific monoclonal antibodies
      (MoAbs), and analyzed with FACSCalibur. RESULTS: The phenytoin-specific
      proliferation of CD4+ cells in patients was significantly higher than in the four
      controls exposed to phenytoin, and in seven healthy children with no previous
      phenytoin intake. A significant difference in the percentages of CD4+ IFN-gamma+
      cells between patients and the seven healthy children was observed. The
      sensitivity and specificity of proliferation were 100% and 90.9%, and those of
      IFN-gamma secretion were 71.4% and 100%, respectively. CONCLUSIONS: Phenytoin
      specific proliferation may be detected with greater sensitivity by the CFSE
      dilution assay than the conventional LTT. The assay revealed that both CD4+ and
      CD4- T cells proliferated and produced IFN-gamma and TNF-alpha after stimulation
      with phenytoin. The CFSE dilution assay might be useful for the diagnosis and
      understanding of drug hypersensitivity.

PMID- 17460443
TI  - IL-10 and RANTES are elevated in nasopharyngeal secretions of children with
      respiratory syncytial virus infection.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) infection causes asthma-like
      symptoms in infants and young children. Although an increase in several mediators
      in the airway during RSV infection has been reported, the mechanisms involved in
      airway inflammation are not fully understood. The aim of this study was to
      investigate the immunological deviation associated with airway inflammation by
      measuring cytokine and chemokine levels in the airway during RSV infection.
      METHODS: One hundred and ten children under 3 years of age with respiratory
      symptoms were enrolled in this study from November 2004 through January 2005.
      Nasopharyngeal secretions (NPAs) were gently aspirated and analyzed with RSV
      antigen, thereafter the concentrations of IL-4, IL-10, IFN-gamma, and RANTES were
      measured using an ELISA kit. We also investigated the prognosis of each child
      after 1 year by reference to clinical records or by interviews and re-evaluated
      the cytokine and chemokine levels. RESULTS: Of the subjects, 70 children were RSV
      positive and 40 were negative. Only 4 children were given a diagnosis of asthma
      by the pediatrician when NPAs were collected. The levels of IL-4, IL-10, and
      RANTES were significantly higher in the RSV-positive patients than RSV-negative
      patients with P values at 0.0362, 0.0007, and 0.0047, respectively. In contrast,
      there was no significant difference in the levels of IFN-gamma. Furthermore,
      there was a significant positive correlation between IL-10 and RANTES.
      CONCLUSIONS: The increased production of IL-4, IL-10, and RANTES in the airway
      may play an important role in the pathophysiological mechanisms of RSV infection.

PMID- 17460444
TI  - Effects of respiratory syncytial virus infection on dendritic cells and cysteinyl
      leukotrienes in lung tissues of a murine model of asthma.
AB  - BACKGROUND: Pulmonary dendritic cells (DCs) play critical roles in both allergy
      and in viral infection. Levels of cysteinyl leukotrienes (cysLTs) increase after
      allergen sensitization and viral infection and can modulate the migration and
      functions of DCs. The present study examines the effects of respiratory syncytial
      virus (RSV) infection on numbers of DCs and cysLT concentrations in lung tissues
      of mice sensitized with mite allergen. METHODS: We examined Control,
      Dermatophagoides farinae allergen sensitized (Df), RSV infected (RSV) and Df
      allergen sensitized and RSV infected (Df-RSV) Balb/c mice. We then determined the
      number of CD11c-positive DCs and the LT concentration in lung tissues of the mice
      and examined lung pathology and cytokine profiles in thoracic lymph nodes.
      RESULTS: Infection with RSV significantly enhanced allergic airway inflammation
      in Df mice with concomitant increases in Th1 and Th2 immunity. The number of DCs
      and the cysLT concentrations were significantly increased in the lungs of Df and
      RSV mice and more so in Df-RSV, than in Df mice. CONCLUSIONS: The present
      findings suggest that RSV infection increases the number of DCs and the cysLT
      concentrations in lung tissues of asthma patients, both of which could result in
      enhanced allergic airway inflammation.

PMID- 17460446
TI  - The impact of the Chuetsu earthquake on asthma control.
AB  - The Impact of the Chuetsu Earthquake on Asthma Control.

PMID- 17460445
TI  - The effect of H1 antagonists carebastine and olopatadine on histamine induced
      expression of CC chemokines in cultured human nasal epithelial cells.
AB  - BACKGROUND: CC chemokines have been shown to play an important role in inducing
      selective recruitment of inflammatory cells into local allergic inflammatory
      sites. CC chemokines are also known as histamine releasing factors. We previously
      showed that histamine enhances transcription of CC chemokines from nasal mucosa
      which leads to further induction of histamine release. This cyclic cascade may
      cause prolonged allergic inflammation. The aim of this study is to clarify the
      relationship between histamine and CC chemokine production by using human nasal
      epithelial cells (HNECs) and to examine the potential of H1 receptor (H1R)
      antagonists in new therapeutic approaches for the treatment of nasal allergy.
      METHODS: HNECs were isolated from the nasal turbinates of patients diagnosed with
      nasal allergy. HNEC monolayers were cultured for 48 hours with or without
      histamine (10(-3) to 10(-5) mol/L). Furthermore, an H1R antagonist, either
      carebastine or olopatadine, was added to the supernatant (10(-3) to 10(-7) mol/L)
      30 minutes before incubation with histamine. The expression of Regulated on
      Activation, Normal T-cell Expressed and Secreted (RANTES) and monocyte
      chemotactic protein-1 (MCP-1) in the culture media were measured by ELISA.
      RESULTS: The release of RANTES and MCP-1 was significantly upregulated by
      histamine compared with the control group. Both carebastine and olopatadine
      inhibited the release of CC chemokine production to the control level in both
      groups. CONCLUSIONS: This study suggests that the interaction between histamine
      and CC chemokines may prolong allergic inflammation in human nasal mucosa. We
      also demonstrate the potential use of H1R antagonists in new therapeutic
      approaches to the treatment of nasal allergy through inhibiting this histamine-CC
      chemokine interaction.

PMID- 17460447
TI  - p16 expression in primary ovarian mucinous and endometrioid tumors and metastatic
      adenocarcinomas in the ovary: utility for identification of metastatic HPV
      related endocervical adenocarcinomas.
AB  - Distinction of primary ovarian epithelial tumors from metastatic adenocarcinomas
      is challenging for tumors exhibiting mucinous, endometrioid, or mixed
      endometrioid/mucinous differentiation. Metastatic carcinomas with these types of
      differentiation can be derived from several sites, including the gastrointestinal
      tract and the uterus. Most endocervical adenocarcinomas exhibit mucinous and/or
      endometrioid differentiation; they infrequently metastasize to the ovaries but
      may simulate primary ovarian tumors [both atypical proliferative (borderline) and
      carcinoma]. Most are high-risk human papillomavirus (HPV)-related and demonstrate
      diffuse p16 over-expression due to complex molecular mechanisms by which high
      risk HPV transforming proteins interact with cell cycle regulatory proteins. The
      performance of this expression pattern for identifying metastatic endocervical
      adenocarcinomas in the ovaries among primary ovarian tumors and other metastatic
      adenocarcinomas having mucinous and/or endometrioid/endometrioidlike
      differentiation has not been evaluated. Immunohistochemical expression of p16 was
      assessed in 195 tumors, including 98 primary ovarian tumors (51 mucinous, 47
      endometrioid, and 4 mixed mucinous-endometrioid tumors), 93 metastatic
      adenocarcinomas of known primary sites (colorectum: 34, endocervix: 19,
      pancreaticobiliary tract: 17, appendix: 7, stomach: 5), 11 metastatic
      adenocarcinomas of unknown origin (7 established as noncervical), and 4
      adenocarcinomas of uncertain (primary ovarian vs. metastatic) origin. The HPV
      status of the endocervical adenocarcinomas was determined by in situ
      hybridization and polymerase chain reaction (when in situ hybridization was
      negative). Expression was assessed based on the percentage of moderately to
      strongly positive cells, estimated to the nearest 10%. Mean and median expression
      values for HPV-positive endocervical adenocarcinomas (99%, 100%; range 90% to
      100%) were substantially higher than those for primary ovarian mucinous (5%, 0%;
      range 0% to 70%) and endometrioid (20%, 10%; range 0% to 100%) tumors, HPV
      unrelated endocervical adenocarcinomas (0%, 0%; range 0% to 60%), metastatic
      adenocarcinomas of unknown origin (11%, 0%; range 0% to 30%), and adenocarcinomas
      of uncertain (primary ovarian vs. metastatic) origin (40%, 35%; range 0% to 90%);
      only the 15 HPV-positive endocervical adenocarcinomas and 6 other tumors had
      values of 80% or greater. Diffuse (>75% positive tumor cells) moderate to strong
      p16 expression is a sensitive (100%) and specific (97%) marker for identifying
      HPV-related endocervical adenocarcinomas metastatic to the ovary among the
      primary ovarian tumors and metastatic adenocarcinomas from other sites that are
      in the differential diagnosis of ovarian tumors having mucinous and/or
      endometrioid/endometrioidlike differentiation. p16 is useful as part of a panel
      of immunohistochemical markers for distinguishing primary ovarian tumors from
      metastases and, when diffusely positive, can suggest the cervix as a potential
      primary site for metastatic adenocarcinomas of unknown origin.

PMID- 17460448
TI  - Gastric morphology and immunophenotype predict poor outcome in mucinous
      adenocarcinoma of the uterine cervix.
AB  - Endocervical-type mucinous adenocarcinoma (ECA) of the uterine cervix is defined
      as a tumor composed of cells resembling those of the endocervical glands, but
      recent studies have demonstrated that a minority of ECAs displays a gastric
      immunophenotype. The aim of this study was to assess the significance of the
      gastric phenotype. Fifty-three cases of mucinous adenocarcinoma of the uterine
      cervix (37 FIGO stage IB, 4 stage IIA, and 12 stage IIB) were reviewed and
      reevaluated using a newly established morphologic criteria for distinguishing
      gastric type adenocarcinoma, which was defined as a tumor showing clear and/or
      pale eosinophilic and voluminous cytoplasm, with distinct cell borders. The
      results were correlated with gastric immunophenotype, determined by HIK1083 and
      MUC6 immunostaining, and patient outcome. Following the current World Health
      Organization scheme (2003), 47 tumors (89%) were classified as ECA, 1 (2%) as
      intestinal type, 1 (2%) as mixed endocervical and intestinal type, and 4 (8%) as
      minimal deviation adenocarcinoma. Twelve of 47 (26%) ECAs and all 4 minimal
      deviation adenocarcinomas, reclassified as gastric type using the novel criteria,
      were frequently positive for HIK1083 with a rate of 75% (12/16), whereas only 11%
      (4/37) of nongastric tumors were positive. There was no significant difference in
      MUC6 reactivity between gastric and nongastric type tumors (31%, 5/16 vs. 16%,
      6/37; P=0.4). Patients with gastric-type adenocarcinomas had a significantly
      decreased 5-year disease-specific survival rate (30 vs. 77%; P<0.0001), and the
      gastric type morphology was related to a significant risk for disease recurrence
      compared with the nongastric type (P=0.001; HR, 4.5; 95% confidence interval,
      1.42-14.2). HIK1083-positivity was also related to decreased 5-year disease
      specific survival rate (38% vs. 74%; P<0.005). Mucinous adenocarcinoma of the
      uterine cervix with gastric immunophenotype can be a distinct morphologic variant
      showing an aggressive clinical course.

PMID- 17460449
TI  - Placental S100 (S100P) and GATA3: markers for transitional epithelium and
      urothelial carcinoma discovered by complementary DNA microarray.
AB  - The morphologic distinction between prostate and urothelial carcinoma can be
      difficult. To identify novel diagnostic markers that may aid in the differential
      diagnosis of prostate versus urothelial carcinoma, we analyzed expression
      patterns in prostate and bladder cancer tissues using complementary DNA
      microarrays. Together with our prior studies on renal neoplasms and normal
      kidney, these studies suggested that the gene for placental S100 (S100P) is
      specifically expressed in benign and malignant urothelial cells. Using tissue
      microarrays, a polyclonal antiserum against S100P protein stained 86% of 295
      urothelial carcinomas while only 3% of 260 prostatic adenocarcinomas and 1% of
      133 renal cell carcinomas stained. A commercially available monoclonal antibody
      against S100P stained 78% of 300 urothelial carcinomas while only 2% of 256
      prostatic adenocarcinomas and none of 137 renal cell carcinomas stained. A second
      gene, GATA3, also showed high level expression in urothelial tumors by cDNA
      array. A commercially available monoclonal antibody against GATA3 stained 67% of
      308 urothelial carcinomas, but none of the prostate or renal carcinomas. For
      comparison, staining was also performed for p63 and cytokeratin 5/6. p63 stained
      87% of urothelial carcinomas whereas CK5/6 stained 54%. Importantly, when S100P
      and p63 were combined 95% of urothelial carcinomas were labeled by one or both
      markers. We conclude that the detection of S100P and GATA3 protein expression may
      help distinguish urothelial carcinomas from other genitourinary neoplasms that
      enter into the differential diagnosis.

PMID- 17460450
TI  - The expression of transforming growth factor-alpha in cirrhosis, dysplastic
      nodules, and hepatocellular carcinoma: an immunohistochemical study of 70 cases.
AB  - The emergence of hepatocellular carcinoma (HCC) is thought to be a stepwise
      process, with high-grade dysplastic nodules (HGDN) representing premalignant
      lesions arising in a background of cirrhosis. Earlier studies have revealed
      altered expression of transforming growth factor-alpha (TGF-alpha) (a mitogen
      capable of inducing hepatocarcinogenesis in mice) in HCC and its surrounding
      parenchyma. DNA topoisomerase II-alpha (Topo II-alpha) is a nuclear protein
      targeted by several chemotherapeutic agents and is overexpressed in HCC. The
      expression of both TGF-alpha and Topo II-alpha in putative preneoplastic
      hepatocytic lesions, however, has not been extensively studied. We examined the
      patterns of TGF-alpha and Topo II-alpha expression in noncirrhotic liver, liver
      cirrhosis, low-grade dysplastic nodules (LGDN), HGDN, and HCC to define the
      possible relationships of these markers to tumor progression. Paraffin sections
      from formalin-fixed material were immunostained with antibodies against TGF
      alpha, Topo II-alpha, and Ki-67. Forty-six HCC, 17 HGDN, and 12 low-grade
      dysplastic nodules were identified in 52 cirrhotic livers from explanted or
      resected specimens. Nuclear staining for Ki-67 and Topo II-alpha was
      significantly increased in the progression from cirrhosis, through HGDN, to HCC,
      whereas the scores for TGF-alpha in these lesions showed an inverse relationship.
      In comparison with 18 HCC arising in noncirrhotic livers, the expression of TGF
      alpha is significantly stronger in cirrhotic liver than in noncirrhotic
      parenchyma and its expression is also stronger in HCC arising in cirrhosis than
      in HCC arising in noncirrhotic parenchyma. The increased expression of Topo II
      alpha and Ki-67 from HGDN to HCC, when compared with cirrhosis, suggests that
      HGDN is a precursor lesion in hepatocarcinogenesis. The inverse relationship
      between these proliferative markers and TGF-alpha expression in these lesions and
      stronger expression of TGF-alpha in HCC arising in cirrhosis suggest that TGF
      alpha may play an important role in the early events of liver carcinogenesis.

PMID- 17460451
TI  - Chromosomal translocations t(4;14), t(11;14) and proliferation rate stratify
      patients with mature plasma cell myelomas into groups with different survival
      probabilities: a molecular epidemiologic study on tissue microarrays.
AB  - Plasma cell myelomas (PMs) exhibit clinical and molecular heterogeneity. To date,
      morphology and immunohistochemistry on bone marrow trephines are of limited value
      to stratify patients into different prognostic categories. However, some
      chromosomal translocations are of prognostic and/or of predictive importance in
      PMs. In this study, the prognostic significance of morphology, CyclinD1
      expression, proliferation index (Mib1) and presence of the translocations
      FGFR3/IgH [t(4;14)] and CCND1/IgH [t(11;14)] are compared in 119 patients with
      PM. Immunohistochemistry and fluorescence in situ hybridization analysis were
      carried out on a tissue microarray containing bone marrow trephines. Hundred and
      one PMs showed a mature morphology whereas 10 were immature. All but one PM
      carrying a translocation showed a mature morphology. Patients with a t(4;14)
      (12%) had a statistically significant shorter 1-year survival (P=0.004), whereas
      those with a t(11;14) (21%) had a trend towards a better clinical outcome.
      CyclinD1 protein expression was not significantly associated with survival.
      Besides the t(4;14), an immature morphology (P<0.001) and a proliferation index
      (Mib1) of more than 10% (P=0.002) were associated with a significantly worse
      outcome. A high occurrence of strong CyclinD1 protein expression in the tumor
      cells was predictive of either a t(11;14) or of a low level amplification of the
      CCND1 gene, suggesting that different molecular mechanisms may have lead to an
      over-expression of the CyclinD1 protein in PMs. These findings demonstrate that a
      high proliferation rate and translocations involving the IgH locus can stratify
      mature PMs into groups with distinct survival probabilities.

PMID- 17460452
TI  - Basal cell carcinoma of the prostate: a clinicopathologic study of 29 cases.
AB  - We studied 29 cases of basal cell carcinoma of the prostate including what others
      call adenoid cystic carcinoma of the prostate. Patients' age ranged from 42 to 89
      (mean 69) years. The most common methods of diagnosis was transurethral resection
      (TURP) (n=29) and needle biopsy (n=9). In 28/29 cases, slides were reviewed and
      24 (86%) cases showed more than 1 pattern: adenoid cysticlike (AC-P) pattern and
      small solid nests with peripheral palisading were the most predominant patterns,
      each seen in 18 cases (64%). Other patterns included: basal cell hyperplasialike
      in 9 cases (32%); small tubules occasionally lined by a hyaline rim in 9 cases
      (32%), with 4 of these cases also demonstrating intermingling cords of cells; and
      large solid nests in 8 cases (28.5%), 5 of which had central necrosis. Fourteen
      cases of small nests and tubules were centrally lined by eosinophilic cells.
      Desmoplasia was noted in 20 (71%) cases. Infiltration around benign glands was
      seen in 10 (36%) cases, with predominantly small nests and AC-P. Invasion of
      thick muscle bundles of the bladder neck was seen in 10 of 21 TURP cases.
      Perineural invasion was noted in 3 cases with AC-P and 1 case of small basaloid
      nests. Perineural and vascular invasion was seen in 2 basal cell carcinomas with
      large basaloid nests. Mitoses ranged from 0 to 60/10 hpf (mean=4). bcl2 was
      diffusely positive in 22/24 (92%) cases. Ki67 ranged from 2% to 80% (mean=23%).
      Ki67 > or =20% was seen in 13 (56.5%) cases, including all patterns except small
      solid nests. Basal cell markers (HMWCK, p63) either: (1) highlighted multiple
      layers of cells in 15/25 (60%) cases with sparing of the inner most luminal
      layer; (2) labeled just the outermost layers in 6/25 (24%) cases; or (3) reacted
      with only a few scattered cells in 4/25 (16%) cases (3 with large solid nests
      with central necrosis, 1 with tubules and cords). Seven patients had RP with: 5/7
      showing extraprostatic extension with 1/5 also showing seminal vesicle
      involvement and 2/5 also with a positive margin; 1/7 having organ confined
      disease; and 1/7 showing no residual disease. An additional 11 cases showed
      extraprostatic extension on TURP with bladder neck invasion (n=10) or
      periprostatic adipose tissue invasion (n=1). Of 29 (65.5%) cases, 19 had follow
      up > 1 year with a mean of 4.3 years (1 to 19 y). Of 19 (77%) cases, 14 had no
      evidence of disease after 1 to 19 (mean 5.8) years. Of 19 patients, 4 locally
      recurred with 2 after TURP, 1 after enucleation, and 1 after RP. Metastases
      developed in 4/29 patients: 1 in lung, 1 in lung and liver, 1 in lung, bone and
      liver, 1 in penile urethra. Basal cell carcinomas are rare tumors with a broad
      morphologic spectrum. These tumors predominantly show an indolent course with
      local infiltrative behavior. A small subset behaves aggressively with local
      recurrences and distant metastases. The most common morphology among those with
      an aggressive behavior is large solid nests more often with central necrosis,
      high Ki67%, and less staining with basal cell markers.

PMID- 17460453
TI  - The pathology of gastric cardia: a prospective, endoscopic, and morphologic
      study.
AB  - "Carditis" (inflammation of the gastric cardiac mucosa) may be associated with
      gastroesophageal reflux disease (GERD), whereas other studies argue that
      Helicobacter pylori could play a significant role in the chronic cardiac damage.
      We examined prospectively histologic features of gastric cardia, esophagitis, and
      H. pylori status in 204 consecutive subjects with GERD symptoms (57.3% male,
      42.7% female mean age 49.2 y) undergoing upper gastrointestinal endoscopy with
      multiple biopsies in the distal esophagus, cardiac region, and stomach. These
      were assessed for esophagitis landmarks [Ismail Beigi grading (g0-3)], gastritis,
      and H. pylori infection (Sydney classification). The average symptom duration was
      10.8 months. Endoscopy showed no erosive disease in 54.5% patients, grade "A"
      esophagitis in 37.6%, "B" in 8%, and "C" in 1 case. Histologic examination
      disclosed g0 in 8.3% patients, g1 in 78.4%, g2 in 12.8%, and g3 in 1; analysis of
      the cardia showed oxyntic mucosa in 27.9% patients and chronic cardiac mucosa
      inflammation in 72.1%. Carditis was significantly related to macroscopic
      esophagitis (P=0.044) and heartburn score (P=0.001). H. pylori cardiac infection
      was present in 27.4% cases (73.2% associated with cardiac mucosa). Gastric H.
      pylori infection was demonstrated in 35% patients. H. pylori in the cardiac
      region was associated with gastric H. pylori infection (P=0.001) and with paucity
      of GERD symptoms (P=0.05). A good correlation between carditis and GERD,
      concerning symptoms and macroscopic esophagitis was found in this study. H.
      pylori-related carditis is likely to be differently compared with the GERD
      related type.

PMID- 17460454
TI  - Lymphohistiocytoid variant of malignant mesothelioma of the pleura: a series of
      22 cases.
AB  - The lymphohistiocytoid variant of diffuse malignant mesothelioma is rare with
      very few cases described in the literature. It is characterized by mesothelial
      cells with a histiocytelike appearance and an associated dense lymphoid
      infiltrate. We studied clinicopathologic features and immunohistochemical
      patterns of a series of 22 cases. The histiocytelike cells had a mesothelial
      immunophenotype: AE1/AE3 (100%), calretinin (100%), CK5/6 (46%), and EMA (52%).
      The prominent lymphoid component showed a cytotoxic T-cell immunophenotype.
      Prognosis was similar to that of a large series of epithelioid diffuse malignant
      mesotheliomas. Formely, it was classified within the sarcomatoid type. We suggest
      that it should be reclassified as an epithelioid variant because of its similar
      behavioural characteristics. There was no evidence of Epstein-Barr virus-related
      infection.

PMID- 17460455
TI  - The clinical significance of lobular neoplasia on breast core biopsy.
AB  - A core biopsy diagnosis of atypical ductal epithelial hyperplasia is upstaged on
      follow-up excisional biopsy (FUEB) to in situ or invasive carcinoma in about 20%
      of cases, thus prompting a FUEB. In contrast, upstaging information for a core
      biopsy diagnosis of pure lobular neoplasia (LN), without mass lesions or other
      risk-associated lesions is less clear. In this retrospective study, we report the
      largest consecutive series of patients who had a breast core biopsy diagnosis of
      LN and a FUEB. Core needle breast biopsies with a diagnosis of LN were retrieved
      from our files for the period 1999 to 2005, yielding 110 patients. One hundred
      and one patients had a follow-up surgical excision. Cases of LN with coexisting
      high-risk lesions (n=9, 10%) were excluded from the study. Patients with
      associated mass lesions all had benign findings (n=15, 16%) and had no impact on
      the study results. The remaining 77 core biopsies had no masses or risk lesions
      and were mammographically Breast Imaging Reporting and Data System 4 (BIRADS) for
      microcalcifications. Overall, 8/77 (10%) of patients with a radiographic BIRADS 4
      image with calcifications and a core biopsy diagnosis of LN on core biopsy were
      upstaged on FUEB to ductal carcinoma in situ or invasive carcinoma. The numbers
      upstaged from core biopsies were as follows: atypical lobular hyperplasia (ALH)
      4/52 (8%), mixed ALH/lobular carcinoma in situ (LCIS) 1/9 (10%), and pure LCIS
      3/16 (19%). A core biopsy of LCIS with neoplastic epithelial calcifications was
      nearly 3 times more likely to be upstaged on FUEB compared with ALH. We conclude
      that a finding of LN on breast core biopsy in a patient with a BIRADS 4 image and
      calcifications is associated with a risk of 8% to 19% of upstaging to a treatable
      disease on FUEB.

PMID- 17460456
TI  - Plexiform angiomyxoid myofibroblastic tumor of the stomach.
AB  - We report 2 cases of plexiform angiomyxoid myofibroblastic tumor of the stomach,
      a tumor entity that has not been described previously. The patients were a 50
      year-old man (case 1) and a 68-year-old man (case 2). In case 1, the patient
      presented with acute abdominal pain. The tumor in case 2 was incidentally found
      at laparoscopic cholecystectomy. Grossly, the tumors were 4.0 cm (case 1) and 4.5
      cm (case 2) in their greatest dimension, and they were recognized as submucosal
      tumors. The tumor caused gastric perforation in case 1. Histologically, the
      tumors extended from the serosa to the submucosa of the gastric wall, showing a
      plexiform growth pattern. Bland spindle tumor cells were observed, and they were
      separated by abundant intercellular myxoid matrix. The stroma was rich in small
      vessels. Immunohistochemically, the tumor cells were positive for alpha-smooth
      muscle actin and muscle actin, and negative for KIT, CD34, and S-100 protein.
      Electron microscopic findings were consistent with the myofibroblastic nature of
      the tumor cells. No mutations were found in the c-kit and platelet-derived growth
      factor receptor alpha genes. Although clinical follow-up data were insufficient,
      the histologic appearances suggested the benign nature of the tumors. However,
      the tumor in case 1 caused gastric perforation and necessitated an emergency
      operation.

PMID- 17460457
TI  - Histologic variants of papillary and follicular carcinomas associated with
      anaplastic spindle and giant cell carcinomas of the thyroid: an analysis of
      rhabdoid and thyroglobulin inclusions.
AB  - We describe the histologic variants of papillary and follicular carcinomas
      associated with 109 spindle and giant cell carcinomas (SGCC) of the thyroid and
      determine the incidence of rhabdoid and thyroglobulin inclusions in these tumors.
      In addition, we searched for rhabdoid and thyroglobulin inclusions in 120
      papillary carcinomas (PC) (all 15 variants included), 23 differentiated
      follicular carcinomas (DFC), (6 with insular pattern), 6 poorly differentiated
      follicular carcinomas (PDFC) and 34 follicular adenomas (FA). The following
      differentiated thyroid carcinomas coexisted with SGCC: 51 (46.8%) PC, (34
      conventional type, 14 tall cell variant and 3 follicular variant), 6 (5.5%) DFC,
      1 follicular carcinoma with insular pattern (0.9%), and 3 oncocytic carcinomas
      (2.8%). Eleven SGCC (10%) and 2 (33%) PDFC showed rhabdoid features, but lacked
      thyroglobulin inclusions. Thyroglobulin inclusions were found in 10 FA (29%), 8
      (17%) follicular variants of PC and in 7 (30.4%) DFC. There were no rhabdoid
      inclusions in any of these differentiated thyroid tumors. Our findings support
      the hypothesis that most SGCC result from dedifferentiation or anaplastic
      transformation although the mechanisms that underlie this transformation remain
      unknown. The finding that only 1 (0.9%) SGCC was associated with follicular
      carcinoma with insular pattern contradicts the opinion that this tumor occupies
      an intermediate position between differentiated and anaplastic carcinomas.
      Rhabdoid features are markers of PDFC and SGCC while thyroglobulin inclusions are
      markers of FA and differentiated thyroid carcinomas with follicular phenotype.

PMID- 17460458
TI  - Distinctive cytogenetic profile in benign metastasizing leiomyoma: pathogenetic
      implications.
AB  - "Benign metastasizing leiomyoma" is the terminology used to describe a
      controversial entity characterized by a proliferation of bland-appearing smooth
      muscle in lung or abdominopelvic lymph nodes. In this report, we describe 5 cases
      of pulmonary-based smooth muscle tumors that are clinically and histologically
      consistent with this entity, and in which we identified consistent chromosomal
      aberrations (19q and 22q terminal deletion in all cases). This cytogenetic
      profile is found in approximately 3% of uterine leiomyoma, but has not been
      described in other types of benign or malignant neoplasia. These findings suggest
      that the nodular pulmonary smooth muscle proliferations termed "benign
      metastasizing leiomyoma," are a genetically distinct entity, which likely
      originate from a biologically distinctive subset of uterine leiomyoma.

PMID- 17460459
TI  - Utility of immunohistochemistry in predicting microsatellite instability in
      endometrial carcinoma.
AB  - Identification of the microsatellite instability (MSI) phenotype in endometrial
      carcinoma is important given that such tumors are the most common noncolorectal
      tumors to occur in hereditary nonpolyposis colorectal cancer syndrome, and may
      bear prognostic relevance. The objective of this study was to assess the utility
      of immunohistochemistry (IHC), a simple and fast technique, in detecting MSI in
      endometrial carcinoma. The study subjects consisted of 90 endometrial carcinoma
      patients with equal representation of MSI-high (MSI-H) and non-MSI-H tumors. MSI
      was tested using the standard polymerase chain reaction-based method and the 5
      NCI-recommended markers. Overall, IHC with MLH1 and MSH2 antibodies detected 69%
      of MSI-H tumors with a specificity of 100%. Adding PMS2 and MSH6 to the antibody
      panel increased the sensitivity to 91% but decreased the specificity to 83%. The
      most common IHC abnormality in MSI tumors was concurrent loss of MLH1/PMS2.
      Assessment of staining was straightforward in most cases but not in all. Staining
      inadequacies existed. Five stains (4 MLH1 and 1 MSH6) were not interpretable
      because of the lack of any internal positive control. Two percent to 10% of the
      cases (depending on the antibody assessed) had only focal weak staining; the
      highest frequency (10%) occurred with MLH1 antibody. PMS2 staining detected 7
      MLH1-staining present MSI-H cases, thus partly accounting for the increased
      sensitivity with the 4-antibody panel. MSH6 staining identified 9 cases with loss
      of MSH6 alone, 6 of 9 were non-MSI-H, thus partly accounting for the decreased
      specificity with the 4-antibody panel. In conclusion, our results suggest that
      IHC is useful in detecting MSI in endometrial carcinoma. Although IHC has a lower
      sensitivity with more apparent staining inadequacies in detecting MSI in
      endometrial carcinoma than it does in colorectal carcinoma, its use in
      endometrial carcinoma may be an important adjunct when screening for hereditary
      cases. In the future, as prognostic and therapeutic implications of MSI phenotype
      become better defined, it may be reasonable to perform IHC for mismatch repair
      proteins in large numbers of endometrial carcinomas.

PMID- 17460460
TI  - Pulmonary disease due to aspiration of food and other particulate matter: a
      clinicopathologic study of 59 cases diagnosed on biopsy or resection specimens.
AB  - Aspiration of particulate matter is a well-recognized complication in debilitated
      patients at autopsy but is not widely recognized in surgical pathology material.
      We have encountered a surprising number of cases on biopsy or resection
      specimens, and most were unsuspected clinically and pathologically. This study
      was undertaken to clarify clinical and pathologic features that facilitate the
      diagnosis of food/particulate matter aspiration pneumonia. Fifty-nine patients
      were identified with an average age of 57 (range 26 to 85), and a male/female
      ratio of 2:1. Common presenting symptoms (information available in 36 cases)
      included dyspnea (14), fever (9), and cough (6). A history of recurrent pneumonia
      was present in 9. Radiographic data were available in 34 cases. Bilateral
      infiltrates or nodules were found in 17 cases, whereas the changes were
      unilateral in 17. Solitary nodules clinically suspicious for neoplasm were
      present in 13. Aspiration was suspected clinically in only 4 of the 45 cases in
      which the clinical impression or differential diagnosis was stated. Predisposing
      factors for aspiration were identified in 32 patients, including esophageal or
      gastric causes (19), drug use (10), and neurologic conditions (6).
      Histologically, bronchiolitis obliterans-organizing pneumonia was present in 52
      (88%) cases, usually in combination with multinucleated giant cells, acute
      bronchopneumonia/bronchiolitis, and/or suppurative granulomas. Foreign material
      was identified in all cases, including most commonly vegetable or food remnants
      (54 cases), and less often talc or microcrystalline cellulose (7), crospovidone
      (4), and kayexalate (2). Particulate matter aspiration pneumonia is a more common
      cause of lung infiltrates and nodules than generally appreciated. The diagnosis
      should be suspected when multinucleated giant cells, acute
      bronchopneumonia/bronchiolitis, and/or suppurative granulomas are found in a
      background of bronchiolitis obliterans-organizing pneumonia. The presence of
      foreign material confirms the diagnosis.

PMID- 17460461
TI  - Caveolin-1 expression is variably displayed in astroglial-derived tumors and
      absent in oligodendrogliomas: concrete premises for a new reliable diagnostic
      marker in gliomas.
AB  - Caveolins are basic constituents of flask-shaped cell membrane microdomains
      (caveolae), which are involved in many cell functions, including signalling,
      trafficking, and cellular growth control. The distribution of caveolae within the
      normal brain and in brain tumors is controversial. In the present study, we
      describe the expression of caveolin-1 (cav-1) in 64 brain tumors of different
      grade, of either astroglial or oligodendroglial origin. All studied astrocitomas
      of any grade (from II to IV) were cav-1 positive, displaying staining patterns
      and intensity specifically associated to the different tumor grades. In all
      glioblastomas and gliosarcomas, cav-1 staining was extremely intense, typically
      localized at the cell membrane and recognized a variable percentage of cells,
      including the majority of spindle cells and palisade-oriented perinecrotic cells.
      In anaplastic astrocytomas, a less intense membrane staining or a cytoplasmic
      dotlike immunoreactivity were present, the latter being almost the exclusive
      pattern observed in diffuse astrocitomas grade II. In contrast to astroglial
      tumors, the striking totality of grade II oligodendrogliomas and the large
      majority of grade III were lacking cav-1 expression. Interestingly, a cav-1
      distribution overlapping the pattern described in tissues was observed also in
      primary cell cultures of human glioblastomas and astrocytomas, and also in one
      established glioblastoma cell line (U251 MG), analyzed by means of confocal
      microscopy and flow cytometry. In conclusion, among astroglial tumors cav-1
      expression varies in distribution, pattern, and intensity specifically according
      to tumor types and grades. The association between tumor progression and a more
      structured membranous pattern of cav-1 expression could suggest the hypothesis of
      a neoplastic shift towards a mesenchymal phenotype, whose behavioral and biologic
      significance worth further studies. Finally, the lack of cav-1 immunoreactivity
      in oligodendrogliomas suggests its concrete application as a useful diagnostic
      marker.

PMID- 17460462
TI  - Lipoid-cell variant of urothelial carcinoma: a clinicopathologic and
      immunohistochemical study of five cases.
AB  - Invasive urothelial carcinoma may present with many deceptive morphologic
      variants. We report the clinicopathologic and immunohistochemical features of 5
      cases of the so-called lipid-cell variant of urothelial carcinoma. The tumors
      occurred in 4 men and 1 women aged from 56 to 80 years. Four cases were developed
      in the bladder and 1 case in the renal pelvis. All cases were revealed by a
      macroscopic hematuria. The tumors were composed of sheets and nests of large
      epithelial cells with an abundant clear multivacuolated cytoplasm mimicking
      lipoblasts. Nuclei were irregular, hyperchromatic, eccentric, and frequently
      indented by cytoplasmic vacuoles. Mucin stains (PAS, Alcian Blue) were negative.
      Tumor cells were strongly stained with cytokeratin 7, cytokeratin 20, and EMA but
      were negative with S-100 protein. In all cases, a usual high-grade urothelial
      carcinoma component was admixed with lipoid tumor cells. Two tumors infiltrated
      the bladder muscle, 2 cases invaded the bladder submucosa, and 1 case invaded the
      renal parenchyma. In the follow-up, despite appropriate surgical treatment, 4
      patients died of the disease and 1 patient is alive without recurrence. Because
      of its rarity and the tumor cells' appearance, the lipoid-cell variant may be
      misdiagnosed and must be distinguished from liposarcoma or signet-ring cell
      carcinoma. In the present series, the lipoid-cell variant of urothelial carcinoma
      was associated with an aggressive behavior and a poor prognosis.

PMID- 17460463
TI  - Ovarian nonsmall cell neuroendocrine carcinoma: a clinicopathologic and
      immunohistochemical study of 11 cases.
AB  - Nonsmall cell neuroendocrine carcinoma (NSCNEC) of the ovary is a rare and
      aggressive tumor commonly associated with other surface epithelial and germ cell
      neoplasms. In this study, we present the clinicopathologic and
      immunohistochemical features of 11 such cases seen at The University of Texas
      M.D. Anderson Cancer Center in a 16-year period (1990 to 2005). Patients ranged
      in age from 22 to 63 years (mean 46.7). The most common presentation was
      abdominal/pelvic pain (6 cases), followed by ascites (2 cases), pelvic mass,
      vaginal bleeding, and abdominal bloating (1 case each). Tumors were mostly
      unilateral, cystic, or solid/cystic and ranged in size from 5 to 26 cm (mean
      16.2). In 8 cases, NSCNEC was associated with other epithelial neoplasms,
      including mucinous neoplasms of low malignant potential, mucinous carcinoma,
      endometrioid carcinoma, mixed endometrioid and mucinous carcinoma, and a high
      grade carcinoma, not otherwise specified. In 2 cases, the tumor was associated
      with a mature cystic teratoma; one of them also containing an invasive moderately
      differentiated adenocarcinoma. A single case was associated with a benign ovarian
      cyst. The latter case had a dermoid cyst in the contralateral ovary. NSCNEC
      represented anywhere from 10% to 90% of the ovarian tumor. Microscopically, the
      neuroendocrine component was usually composed of large and/or intermediate oval
      to round cells. In 2 cases, the intermediate cells were intermixed with small
      cells. Three cases had also spindle cells. The neoplastic cells were mostly
      arranged in a solid pattern, nests, or trabeculae. All tumors had a brisk mitotic
      activity. Immunoperoxidase studies for keratin cocktail, cytokeratin (CK) 7,
      CK20, CAM 5.2, chromogranin A, synaptophysin, NSE, CD56, and c-kit were performed
      and the cases stained as follows: keratin cocktail 6/6, CK7 4/5, CK20 3/5, CAM
      5.2 3/3, chromogranin A 8/11, synaptophysin 9/9, NSE 1/1, CD56 4/8, and c-kit
      5/7. According to the International Federation of Gynecology and Obstetrics
      staging system, 4 cases were stage I tumors, 3 cases were stage III tumors, and 4
      cases were stage IV tumors. Seven patients were treated with total abdominal
      hysterectomy and bilateral salpingo-oophorectomy followed by chemotherapy. One
      patient had a bilateral salpingo-oophorectomy with omentectomy and appendectomy
      followed by chemotherapy; 1 patient had a total abdominal hysterectomy with right
      salpingo-oophorectomy followed by chemotherapy; one had a bilateral salpingo
      oophorectomy followed by chemotherapy, and one had a right salpingo-oophorectomy
      with appendectomy followed by chemotherapy. Five patients died of disease at 2,
      3, 9, 20, and 36 months. One patient is alive with disease at 8 months and 5 are
      alive without evidence of disease at 11, 28, 37, 66, and 68 months. Four of 5
      patients who died of disease had either stage III or IV tumors and 3 of 5
      patients who are alive without evidence of disease have stage I tumors. In
      summary, ovarian NSCNEC is an aggressive tumor with a tendency to present at
      advanced stage and cause death within a mean of 17 months after diagnosis;
      however, some patients, particularly those with stage I disease and/or those who
      have received platinum-based therapy, may have a more favorable prognosis.

PMID- 17460464
TI  - Histologic characteristics and prognostic significance in small hepatocellular
      carcinoma with biliary differentiation: subdivision and comparison with ordinary
      hepatocellular carcinoma.
AB  - The morphologic characteristics and biologic behavior of small liver cancers with
      hepatic and biliary differentiation, and their histogenesis, remain unclear. In
      this study, 35 cases of hepatocellular carcinoma (HCC) smaller than 3 cm in
      diameter with biliary differentiation were divided into 3 groups, group 1
      [cytokeratin (CK) 19-negative/mucin-negative], group 2 (CK 19-positive/mucin
      negative), and group 3 (CK 19-positive/mucin-positive). Sixty-one HCCs without
      biliary differentiation were used as controls. We compared the histologic
      features of these tumors and the postoperative outcomes. Three morphologic
      features of HCCs with biliary differentiation were respectively observed in 40%
      (14/35), 60% (21/35), and 42.9% (15/35) as follows: (1) cancer cells with
      intermediate morphology, (2) prominent inflammatory cell infiltrate, (3)
      desmoplastic stroma; neural cell adhesion molecule and c-kit expression were
      noted in 25.7%(9/35) and 8.6%(3/35), respectively. Extrahepatic tumor recurrence
      after surgery occurred in 0% (0/16) of group 1, 33.3% (3/9) of group 2, 40.0%
      (4/10) of group 3, and 8.2% (5/61) of the ordinary HCCs. The tumor-related
      survival of group 3 patients was worse than that of patients with ordinary HCCs,
      but there were no differences between the survival of group 1, or group 2
      patients and those with ordinary HCCs. Our results suggest that the biliary
      differentiation does occur even in small HCC, and a mucin-producing cancer cells
      indicates aggressive tumor behavior. The combination of intermediate cancer
      cells, inflammatory cell infiltrate, and desmoplastic stroma is likely to be
      related to the biliary differentiation of HCC.

PMID- 17460465
TI  - Extranodal marginal zone B-cell lymphomas of the ocular adnexa: multiparameter
      analysis of 34 cases including interphase molecular cytogenetics and PCR for
      Chlamydia psittaci.
AB  - Extranodal marginal zone B-cell lymphomas of MALT type (MALT lymphomas) show site
      dependent variations in their morphologic, phenotypic, and/or cytogenetic
      findings. This report describes a comprehensive analysis of 34 ocular adnexa MALT
      lymphomas, including interphase fluorescence in situ hybridization for MALT
      lymphoma-associated cytogenetic abnormalities and polymerase chain reaction for
      Chlamydia psittaci, which has recently been suggested to be associated with
      ocular adnexa lymphomas. A typical morphologic pattern was identified in 79% of
      cases, while overtly monocytoid cytology (12%), predominantly plasmacytic
      features (9%), and lymphoepithelial lesions (3%) were uncommon. Aberrant CD43 or
      CD5 expression was also uncommon (12% and 3%, respectively). Plasmacytic
      differentiation (41%) was associated with stage IV disease (P=0.036) and gains of
      chromosomes 3 and/or 18q (P=0.021) (79%). +3 was more frequent in the orbit than
      in lacrimal gland or conjunctiva (P=0.005). Each of 31 cases was negative for
      MALT1 translocations. IGH translocations were identified in 3 cases (10%),
      although the translocation partner gene could not be identified. Polymerase chain
      reaction assays targeting species-specific regions within the C. psittaci omp1
      and omp2 genes were negative in each of 30 cases. This study identifies the
      characteristic morphologic, phenotypic, and cytogenetic findings in ocular adnexa
      MALT lymphoma, including a subset differing from those arising at other anatomic
      sites. The frequent presence of +3 and/or +18q suggests that these abnormalities
      may contribute to lymphomagenesis. The lack of C. psittaci in this series, in
      contrast to some prior reports, indicates that there may also be geographic
      heterogeneity in the pathogenesis of ocular adnexa MALT lymphoma.

PMID- 17460466
TI  - Granulomatous slack skin with a translocation t(3;9)(q12;p24).
AB  - Granulomatous slack skin is a rare cutaneous T-lymphoproliferative disease
      characterized by pendulous skin folds. Histology typically reveals a dermal
      infiltrate of T cells and multinucleated giant cells showing elastophagocytosis.
      Specific genetic abnormalities have not yet been identified. Currently,
      granulomatous slack skin is classified according to the World Health Organization
      classification as a variant of mycosis fungoides although supporting genetic
      evidence is yet lacking. We present a well-documented case of a 46-year-old man
      with the typical histologic and clinical findings of granulomatous slack skin.
      Cytogenetic analysis of a skin biopsy revealed a t(3;9)(q12;p24) as the sole
      chromosomal abnormality. Fluorescence in situ hybridization analysis did not
      reveal involvement of the JAK2 gene, located at chromosome band 9p24, and
      previously shown to be amplified in Hodgkin lymphoma and primary mediastinal
      diffuse large B-cell lymphoma. Although more cases have to be reported and the
      putative oncogene involved in the translocation has yet to be identified, the
      cytogenetic findings are unlike those described for mycosis fungoides and
      suggests that granulomatous slack skin is a distinct primary cutaneous T-cell
      lymphoma.

PMID- 17460467
TI  - Malignant myoepithelioma of cranial dura.
AB  - Malignant tumors of myoepithelial origin have been increasingly recognized at a
      variety of sites. Herein, we describe an example of malignant myoepithelioma
      arising in intracranial dura. The patient is a 47-year-old woman who presented
      with intracranial hemorrhage and on magnetic resonance imaging was found to have
      an enhancing tumor. No extracranial primary tumor was identified. A gross total
      resection was performed. Histologically, it varied in pattern from diffuse to
      focally (<10%) ductular and consisted of epitheloid to spindle cells showing
      marked mitotic activity. Prominent infiltration of the dura was noted.
      Immunohistochemical stains showed convincing expression of cytokeratins (AE1/AE3
      and CAM 5.2), S-100 protein, smooth muscle actin, and glial fibrillary acidic
      protein. Electron microscopy performed on formalin-fixed, paraffin-embedded
      tissue demonstrated cohesive cells with focal intermediate filament content and
      surface basal lamina formation at stromal interfaces. Occasional desmosomes with
      tonofilaments surrounded intercellular lumina containing masses of filamentous
      material. This example of malignant myoepithelioma is the first convincing
      primary salivary gland type tumor to arise in an intracranial location outside
      the sellar region or ear. Intracranial dura should be added to various sites at
      which this morphologically heterogenous tumor may arise.

PMID- 17460468
TI  - Clonality in juvenile xanthogranuloma.

PMID- 17460469
TI  - HIV-infected patients receiving lopinavir/ritonavir-based antiretroviral therapy
      achieve high rates of virologic suppression despite adherence rates less than
      95%.
AB  - BACKGROUND: The observation that extremely high levels of medication adherence
      are required to achieve complete virologic suppression is based largely on
      studies of treatment-experienced patients receiving HIV protease inhibitor (PI)
      based therapy without ritonavir boosting. This study aims to define the level of
      adherence needed to achieve virologic suppression in patients receiving boosted
      PI-based highly active antiretroviral therapy (HAART) with lopinavir/ritonavir.
      METHODS: HIV-infected adults receiving a regimen containing lopinavir/ritonavir
      were recruited into a prospective, observational study of the relation between
      adherence to lopinavir/ritonavir and virologic outcomes. Adherence was measured
      using the Medication Event Monitoring System (MEMS; Aardex, Union City, CA). HIV
      1 viral load (VL) was measured at week 24. RESULTS: The final study population
      contained 64 subjects. Eighty percent had AIDS, 97% received lopinavir/ritonavir
      before enrollment, and most had more than 7 years of HAART experience. Mean
      adherence overall was 73%. Eighty percent and 59% achieved a VL <400 copies/mL
      and a VL <75 copies/mL, respectively. Mean adherence was 75% in those achieving a
      VL <75 copies/mL. High rates of virologic suppression were observed in all
      adherence quartiles, including the lowest quartile (range of adherence: 23.5%
      53.3%). CONCLUSIONS: Moderate levels of adherence can lead to virologic
      suppression in most patients taking lopinavir/ritonavir-based HAART.

PMID- 17460470
TI  - Association of serum lipid levels with HIV serostatus, specific antiretroviral
      agents, and treatment regimens.
AB  - BACKGROUND: The effects of HIV infection, highly active antiretroviral therapy
      (HAART), and specific antiretroviral agents on lipoproteins in women are not well
      described. METHODS: In a cross-sectional substudy of the Women's Interagency HIV
      Study with 623 HIV-negative and 1556 HIV-positive women (636 untreated, 419 on
      non-protease inhibitor [PI] HAART, and 501 on PI-containing HAART), we performed
      multivariate analyses of associations among fasting lipoprotein levels, HIV
      infection, and HAART. RESULTS: Untreated HIV-positive women had lower high
      density lipoprotein cholesterol (HDL-C) and higher triglycerides (TGs) but not
      lower low-density lipoprotein cholesterol (LDL-C) than HIV-negative women and
      were the most likely to have unfavorable HDL-C by National Cholesterol Education
      Program (NCEP) guidelines. PI HAART users had higher LDL-C than untreated HIV
      infected women (107 vs. 100 mg/dL, P = 0.0006) and were the most likely to have
      unfavorable LDL-C and TGs by NCEP guidelines. HIV-negative women and non-PI HAART
      users had similar HDL-C levels (55 and 53 mg/dL, respectively), which were higher
      than those in untreated HIV-infected women and PI HAART users (42 and 49 mg/dL,
      respectively; P < 0.001 for all). Lamivudine, didanosine, nevirapine, and
      efavirenz were independently associated with higher HDL-C (P < 0.001 for all).
      Ritonavir, indinavir/ritonavir, and nelfinavir were associated with higher LDL-C
      (P < 0.01 for all). Stavudine, abacavir, and all ritonavir-containing regimens
      were associated with higher TGs (P < 0.05 for all), and tenofovir was associated
      with lower TGs (P = 0.009). CONCLUSIONS: A dyslipidemic pattern was associated
      with HIV infection itself, was more severe in users of PI-containing HAART, but
      was not present in women taking non-PI HAART.

PMID- 17460471
TI  - Discordant responses to potent antiretroviral treatment in previously naive HIV-1
      infected adults initiating treatment in resource-constrained countries: the
      antiretroviral therapy in low-income countries (ART-LINC) collaboration.
AB  - OBJECTIVES: To assess the frequency of and risk factors for discordant responses
      at 6 months on highly active antiretroviral therapy (HAART) in previously
      treatment-naive HIV patients from resource-limited countries. METHODS: The
      Antiretroviral Therapy in Low-Income Countries Collaboration is a network of
      clinics providing care and treatment to HIV-infected patients in Africa, Latin
      America, and Asia. Patients who initiated therapy between 1996 and 2004, were
      aged 16 years or older, and had a baseline CD4 cell count were included in this
      analysis. Responses were defined based on plasma viral load (PVL) and CD4 cell
      count at 6 months as complete virologic and immunologic (VR(+)IR(+)), virologic
      only (VR(+)IR(-)), immunologic only (VR(-)IR(+)), and nonresponse (VR(-)IR(-)).
      Multinomial logistic regression was used to assess the association between
      therapy responses and clinical and demographic variables. RESULTS: Of the 3111
      patients eligible for analysis, 1914 had available information at 6 months of
      therapy: 1074 (56.1%) were VR(+)IR(+), 364 (19.0%) were VR(+)IR(-), 283 (14.8%)
      were (VR(-)IR(+)), and 193 (10.1%) were VR(-)IR(-). OF THE 3111 patients eligible
      for analysis, 1914 had available information at 6 months of therapy: 1074 (56.1%)
      were VRIR, 364 (19.0%) were VRIR, 283 (14.8%) were (VRIR), and 193 (10.1%) were
      VRIR. Compared with complete responders, virologic-only responders were older,
      had a higher baseline CD4 cell count, had a lower baseline PVL, and were more
      likely to have received a nonstandard HAART regimen; immunologic-only responders
      were younger, had a lower baseline CD4 cell count, had a higher baseline PVL, and
      were more likely to have received a protease inhibitor-based regimen.
      CONCLUSIONS: The frequency of and risk factors for discordant responses were
      comparable to those observed in developed countries. Longer follow-up is needed
      to assess the long-term impact of discordant responses on mortality in these
      resource-limited settings.

PMID- 17460472
TI  - Prevalence of and risk factors for pubic lipoma development in HIV-infected
      persons.
AB  - BACKGROUND: The natural history of HIV-associated body habitus changes is
      unclear. In this report, we describe a novel manifestation of HIV-associated
      lipoaccumulation. METHODS: We noted the presence of suprapubic fat pads (pubic
      lipomas [PLs]) in several patients with preexisting HIV-associated body habitus
      abnormalities. Subsequently, we evaluated the prevalence of and associated risk
      factors for development of PLs by undertaking an observational cross-sectional
      study among patients with known lipodystrophy who attended a metabolic clinic in
      northern Italy. Inclusion criteria were a physician-confirmed diagnosis of
      lipodystrophy according to the Multicenter AIDS Cohort Study definition and, for
      those affected with PL, a readily noticeable PL on physical examination. RESULTS:
      We evaluated 582 patients with lipodystrophy: 214 female (36.7%) and 368 male
      (63.3%). The overall PL prevalence was 9.4% (95% confidence interval [CI]: 7.2%
      to 12.1%; P < 0.0001). PLs were more common among obese than nonobese individuals
      (34.5%, 95% CI: 17.9% to 5l.3% vs. 8%, 95% CI: 5.9% to 10.6%, respectively; P <
      0.0001) and those with preexisting dorsocervical fat pads, commonly called
      "buffalo humps" (BHs) (18.5%, 95% CI: 12.7% to 25.4% vs. 6.1%, 95% CI: 4.03% to
      8.83%, respectively, P < 0.0001; relative risk = 3.02, 95% CI: 1.84% to 4.96%, P
      < 0.0001). The PL prevalence in the nonobese HIV-infected population (body mass
      index [BMI] <30, n = 550) was 8.0% (95% CI: 5.9% to 10.6%; P < 0.0001). Logistic
      regression analyses identified the following factors as associated with a greater
      likelihood for PL: BMI >30 (beta = 0.18, SE = 0.04; P < 0.001), female gender
      (beta = 1.06, SE = 0.31; P < 0.001), and shorter duration of HIV infection (beta
      = -0.005, SE = 0.003; P = 0.04). We used a chain graph model to evaluate risk
      factors for BH and PL simultaneously. A nonnull interaction between these
      entities was evident, and this association seemed to be independent of factors
      positively associated with both (BMI and gender). CONCLUSIONS: PL is a newly
      recognized manifestation of HIV-associated lipoaccumulation that is more likely
      to occur among those with coexisting dorsocervical fat pads, suggesting the
      possibility of a common pathogenesis between the 2 entities. Likewise, PLs are
      more common among women, obese individuals, and those with a shorter duration of
      HIV infection. We suggest that PL should be considered part of the HIV-associated
      lipodystrophy syndrome.

PMID- 17460473
TI  - Successful introduction of routine opt-out HIV testing in antenatal care in
      Botswana.
AB  - BACKGROUND: Botswana has high HIV prevalence among pregnant women (37.4% in 2003)
      and provides free services for prevention of mother-to-child transmission (PMTCT)
      of HIV. Nearly all pregnant women (>95%) have antenatal care (ANC) and deliver in
      hospital. Uptake of antenatal HIV testing was low from 1999 through 2003. In
      2004, Botswana's President declared that HIV testing should be "routine but not
      compulsory" in medical settings. METHODS: Health workers were trained to provide
      group education and recommend HIV testing as part of routine ANC services.
      Logbook data on ANC attendance, HIV testing, and uptake of PMTCT interventions
      were reviewed before and after routine testing training, and ANC clients were
      interviewed. RESULTS: After routine testing started, the percentage of all HIV
      infected women delivering in the regional hospital who knew their HIV status
      increased from 47% to 78% and the percentage receiving PMTCT interventions
      increased from 29% to 56%. ANC attendance and the percentage of HIV-positive
      women who disclosed their HIV status to others remained stable. Interviews
      indicated that ANC clients supported the policy. CONCLUSIONS: Routine HIV testing
      was more accepted than voluntary testing in this setting and led to substantial
      increases in the uptake of testing and PMTCT interventions without detectable
      adverse consequences. Routine testing in other settings may strengthen HIV care
      and prevention efforts.

PMID- 17460474
TI  - Needle exchange and injection-related risk behaviors in Chicago: a longitudinal
      study.
AB  - OBJECTIVE: To examine whether needle exchange program (NEP) use by injecting drug
      users (IDUs) affects injection risk behaviors over time. METHODS: Between 1997
      and 2000, 901 IDUs in Chicago were recruited for a cohort study from a multisite
      NEP and an area with no NEP. Participants were interviewed and tested for HIV at
      baseline and 3 annual follow-ups. Non-NEP users received HIV prevention services
      consistent with the Indigenous Leader Outreach Model. Random-effect logistic
      models were used to compare 5 injection-related risk behaviors between NEP users
      and nonusers. RESULTS: The 30-day prevalence of receptive needle sharing
      decreased from 27.6% at baseline to 10.0% at visit 4 in NEP users and from 47.1%
      to 20.0% in nonusers. Similar patterns were observed for lending used needles,
      and NEP users were less likely to reuse their own needles. In multivariate
      analyses, NEP use was significantly associated with reduced odds of greater than
      60% for receptive needle sharing, 45% for lending used needles, and 30% for
      sharing other injection paraphernalia as well as approximately a 2-fold increase
      in the odds of always bleaching used needles. CONCLUSIONS: NEP use facilitates
      long-term reductions in injection risk practices, and the reductions are in
      addition to the effects of a behavioral intervention alone.

PMID- 17460475
TI  - Do tests devised to detect recent HIV-1 infection provide reliable estimates of
      incidence in Africa?
AB  - The objective of this study was to assess the performance of 4 biologic tests
      designed to detect recent HIV-1 infections in estimating incidence in West Africa
      (BED, Vironostika, Avidity, and IDE-V3). These tests were assessed on a panel of
      135 samples from 79 HIV-1-positive regular blood donors from Abidjan, Cote
      d'Ivoire, whose date of seroconversion was known (Agence Nationale de Recherches
      sur le SIDA et les Hepatites Virales 1220 cohort). The 135 samples included 26
      from recently infected patients (< or =180 days), 94 from AIDS-free subjects with
      long-standing infection (>180 days), and 15 from patients with clinical AIDS. The
      performance of each assay in estimating HIV incidence was assessed through
      simulations. The modified commercial assays gave the best results for sensitivity
      (100% for both), and the IDE-V3 technique gave the best result for specificity
      (96.3%). In a context like Abidjan, with a 10% HIV-1 prevalence associated with a
      1% annual incidence, the estimated test-specific annual incidence rates would be
      1.2% (IDE-V3), 5.5% (Vironostika), 6.2% (BED), and 11.2% (Avidity). Most of the
      specimens falsely classified as incident cases were from patients infected for
      >180 days but <1 year. The authors conclude that none of the 4 methods could
      currently be used to estimate HIV-1 incidence routinely in Cote d'Ivoire but that
      further adaptations might enhance their accuracy.

PMID- 17460476
TI  - Early virologic failure in HIV-coinfected hepatitis C patients treated with the
      peginterferon-ribavirin combination: does abacavir play a role?

PMID- 17460477
TI  - Could tenofovir modify the model end-stage liver disease (MELD) score in patients
      with end-stage liver disease eligible for liver transplantation?

PMID- 17460478
TI  - Expanded services for the prevention of mother-to-child HIV transmission: field
      acceptability of a pilot program in Lusaka, Zambia.

PMID- 17460480
TI  - Response to "Micronutrient supplementation increases CD4 count in HIV-infected
      individuals on highly active antiretroviral therapy: a prospective, double
      blinded, placebo-controlled trial".

PMID- 17460483
TI  - Rotavirus and celiac disease: clues to the pathogenesis and perspectives on
      prevention.

PMID- 17460484
TI  - Functional consequences of NOD2/CARD15 mutations in Crohn disease.
AB  - Crohn disease (CD) is a chronic, relapsing inflammatory disorder of the
      gastrointestinal tract. Its etiology remained obscure until recently, when,
      through an overwhelming body of research, the main theme of its origin became
      clear. CD develops in individuals who carry risk alleles for the disease that can
      cause a loss of physiological tolerance to commensal bacteria. As a consequence,
      immune responses develop that activate a whole range of immunocompetent cells,
      resulting in the secretion of proinflammatory mediators that ultimately cause
      mucosal breaks and the formation of ulceration, edema, and loss of proper
      function.

PMID- 17460485
TI  - Quality of life in paediatric gastrointestinal and liver disease: a systematic
      review.
AB  - OBJECTIVES: To identify and appraise all studies relating to and instruments
      developed to measure quality of life (QOL) in children with gastrointestinal or
      liver diseases. METHODS: A literature search was undertaken using MEDLINE,
      EMBASE, CINAHL, and PsycINFO to identify relevant articles published up to the
      end of 2005. These were reviewed by both authors and data were extracted using a
      standardised form. Articles were excluded if no attempt was made to measure QOL,
      they did not relate to children ages <17 years, they did not relate to
      gastrointestinal or liver diseases, or they were review articles. Quality of life
      instruments identified were rated according to proposed criteria. RESULTS: From a
      total of 2379 articles identified in the initial search, a total of 2309 were
      excluded, leaving 70 included studies. These were assigned to the following
      categories: inflammatory bowel disease, n = 17; cystic fibrosis, n = 20; liver
      disease, n = 11; surgery, n = 15; and miscellaneous, n = 7. These studies
      describe the impact that these diseases have on the QOL of affected children. A
      total of 11 disease-specific QOL instruments and 1 generic instrument with a
      chronic disease module were identified, but only 5 of these fulfilled the
      proposed quality criteria and can be recommended for future use. CONCLUSIONS:
      Chronic gastrointestinal and liver diseases can have an enormous effect on the
      QOL of affected individuals and their families. A number of disease-specific
      paediatric QOL instruments have been developed and validated. Quality of life is
      an important outcome that should be incorporated into clinical practice and
      measured when treatments are evaluated. Future research should explore how QOL
      can best be improved in children in whom it is severely impaired.

PMID- 17460486
TI  - Disease presentation and clinical course in black and white children with
      inflammatory bowel disease.
AB  - OBJECTIVES: To compare the disease presentation, disease phenotype, and clinical
      course between black and white children with inflammatory bowel disease (IBD).
      PATIENTS AND METHODS: A 10-year retrospective review was undertaken of the
      medical records of 245 pediatric patients with IBD studied at a tertiary care
      center. RESULTS: In this patient population 24% were black and 76% were white.
      There were no differences between black and white patients in terms of anatomic
      distribution of IBD, symptom presentation, and extraintestinal manifestations. A
      family history of IBD (36.4% vs 17.5%; P = 0.006) was more common in white
      children. Mean erythrocyte sedimentation rate of black patients with Crohn
      disease was higher at diagnosis compared with whites (P < 0.001) and a greater
      proportion of African Americans presented with a body mass index z-score less
      than -2 (P < 0.009). At 12 months following diagnosis 22.5% of African American
      children had a hemoglobin level lower than 10 g/dL compared with 4.3% of whites
      (P = 0.001). African Americans had evidence of more complicating stricturing and
      penetrating Crohn disease behavior (51.3% vs 27.4%; P = 0.006). African Americans
      received significantly more corticosteroids and infliximab to treat their IBD
      compared with whites (P < 0.04). CONCLUSIONS: This study suggests that for
      pediatric IBD, there may be racial differences in prevalence of family history
      and in disease phenotype.

PMID- 17460487
TI  - Effects of the probiotic formulation VSL#3 on colitis in weanling rats.
AB  - BACKGROUND: Only a few studies have used models of inflammatory bowel disease
      (IBD) with weanling animals. Previously, the effects of probiotics have not been
      assessed in such IBD models. The objectives of our study were 2-fold: to
      establish a suitable model of dextran sulfate sodium (DSS)-induced colitis in
      weanling rats and to determine the effects of the probiotic formulation VSL#3 on
      DSS-induced colitis in weanling animals. MATERIALS AND METHODS: Rats were weaned
      on postnatal day 21 and administered 2%, 2.5%, or 3% (wt/vol) DSS in drinking
      water. In subsequent experiments, newly weaned animals were administered vehicle
      or VSL#3 (0.06, 0.6, or 6 mg) by orogastric gavage. These treatments were given
      to animals maintained on water (postnatal days 21-28) and then on DSS (postnatal
      days 28-35). Disease activity indices were determined on a routine basis. On day
      35, rats were euthanized. The total colon length was determined. Other parameters
      of colitis were measured from the distal colon. These parameters included
      myeloperoxidase (MPO), interleukin (IL)-1beta, inhibitory kappaB-alpha (IkappaB
      alpha), and histological assessment of crypt damage and inflammation. RESULTS:
      DSS 2% was optimal for inducing colitis in weanling rats without significant
      morbidity. VSL#3 treatments improved various parameters of 2% DSS-induced colitis
      in weanling rats. The 0.6- and 6-mg doses of VSL#3 were most effective for
      attenuating this colitis. CONCLUSIONS: The probiotic formulation VSL#3 improved
      DSS-induced colitis in weanling rats. This improvement of colitis involved
      changes in colonic IkappaB-alpha, IL-1beta, and MPO, which are suggestive of
      immune modulation by VSL#3.

PMID- 17460488
TI  - Effectiveness and safety of Lactobacillus LB in the treatment of mild acute
      diarrhea in children.
AB  - BACKGROUND: Acute diarrhea is an important cause of morbidity and mortality in
      children. Oral rehydration salts (ORS) have lowered mortality without having an
      effect on the duration or severity of diarrhea. Some studies have reported that
      heat-killed Lactobacillus bacteria have a beneficial effect in the treatment of
      acute diarrhea. In this placebo-controlled study the duration of diarrhea was
      compared for 2 types of treatment: Lactobacillus LB (Lacteol) in association with
      oral rehydration and oral rehydration alone. PATIENTS AND METHODS: A total of 80
      nondehydrated children between the ages of 3 months and 4 years with acute watery
      diarrhea were randomly assigned to be treated with Lactobacillus LB or placebo
      plus ORS. The primary endpoint was the duration of diarrhea; intake of ORS and
      change in body weight between the time of randomization and the last assessment
      were also measured. RESULTS: In 71 of the 80 patients, diarrhea was resolved: 36
      in the Lactobacillus LB group and 35 in the placebo group. Several clinical
      characteristics of the 2 treatment groups were comparable at baseline. Median
      duration of diarrhea was 16.6 hours in the placebo group compared with 10.0 hours
      in the Lactobacillus LB group (P = 0.275). In the subgroup with a duration of
      diarrhea of more than 24 hours at inclusion, duration of diarrhea measured from
      that point was shorter for the Lactobacillus LB group (30.4 h vs 8.2 h; P =
      0.044). ORS intake was similar for both groups. Lactobacillus LB was well
      tolerated, with only one patient experiencing an adverse effect. CONCLUSIONS:
      Lactobacillus LB is an effective and safe treatment for children with well
      established diarrhea (>24 h).

PMID- 17460489
TI  - Conditions of bifidobacterial colonization in preterm infants: a prospective
      analysis.
AB  - BACKGROUND: Premature birth results in a delayed and abnormal qualitative pattern
      of gut colonization. This abnormal pattern is thought to affect intestinal
      development and contribute to a higher risk of gastrointestinal infectious
      diseases such as neonatal necrotizing enterocolitis (NEC). In particular,
      bifidobacteria are thought to play a major role. We therefore studied
      bifidobacterial colonization in preterm infants during the first month of life.
      PATIENTS AND METHODS: Fecal samples were prospectively analyzed in 52 infants
      born at a gestational age ranging from 30 to 35 weeks fed with a preterm formula
      alone and, in 18, with their mother's milk. Fecal samples were collected twice
      per week during the hospital stay. Bifidobacterial colonization was analyzed with
      culture and a molecular method. RESULTS: Bifidobacterial colonization occurred in
      18 infants at a median age of 11 days, always greater than the corrected mean
      gestational age of 35.4 weeks (SD, 0.9) and greater than 34 weeks for 16 of 18.
      Colonization by bifidobacteria was affected by neither birthweight nor mode of
      delivery nor antibiotics given to the mother or infant. In contrast, birth
      gestational age had a significant impact on colonization by bifidobacteria (P <
      0.05), which always occurred in children born at a birth gestational age greater
      than 32.9 weeks (P < 0.05). CONCLUSIONS: Birth gestational age seems to act as a
      major determinant of bifidobacterial colonization in the premature infant,
      suggesting the role of gut maturation, a finding that should probably be taken
      into account in manipulations of the gut flora aimed at reducing NEC.

PMID- 17460490
TI  - Tissue transglutaminase antibodies are a useful serological marker for the
      diagnosis of celiac disease in patients with Down syndrome.
AB  - BACKGROUND: Celiac disease (CD) is overrepresented among patients with Down
      syndrome (DS), who frequently lack any typical symptoms. Therefore, screening for
      CD is recommended in this high-risk group. The aim of the study was to determine
      the prevalence of CD in Arab children with DS and evaluate the contribution of
      immunoglobulin (Ig) A and IgG anti-gliadin antibodies (AGA), IgA and IgG tissue
      transglutaminase (TTG) antibodies, and IgA anti-endomysial antibodies (EMA) to
      screen for CD in children with DS. PATIENTS AND METHODS: A total of 52 Arab
      patients with DS and 52 healthy Arab control subjects were studied for CD using
      various serological markers. Data on age, sex, weight, height, gastrointestinal
      symptoms, and endocrine abnormalities were recorded. Human leukocyte antigen
      (HLA) was studied in patients undergoing small intestinal biopsy. RESULTS: Five
      patients with DS were IgA TTG-positive and only 1 patient with DS was IgG TTG
      positive. EMA was negative in all patients with DS. TTG (IgA and IgG) and EMA
      were negative in all control children. IgA AGA was positive in 12 patients with
      DS and 3 control subjects (P = 0.02), whereas IgG AGA was positive in 41 patients
      with DS and 26 control subjects (P = 0.004). Only children testing positive for
      TTG underwent upper endoscopy with duodenal biopsy. Two children with DS were
      diagnosed with CD. Both patients were IgA TTG-positive. One was HLA DQ2-positive
      and another was negative for HLA DQ2 and DQ8. CONCLUSIONS: CD is prevalent (3.8%)
      in Arab patients with DS. Based on our cohort, IgA TTG is useful in diagnosing
      patients with CD and DS.

PMID- 17460491
TI  - Minimally invasive surgery for achalasia: combined experience of two European
      centers.
AB  - BACKGROUND: The present report summarizes 12 cases with achalasia treated with
      laparoscopic Heller myotomy and anterior fundoplication according to the method
      of Thal and Dor. PATIENTS AND METHODS: From 1997 to 2005 at 2 institutions in
      Europe, 12 patients (7 male and 5 female, ages ranging from 3.5 to 7 years) were
      treated for esophageal achalasia (EA) with laparoscopic Heller myotomy and
      anterior fundoplication according to Thal and Dor. In 1 case a perforation of the
      esophageal mucosa occurred, which was promptly treated during surgery. Follow-up
      ranged from 18 to 60 months and included clinical examination and barium
      radiography of the upper digestive tract. RESULTS: Postoperatively, 10 patients
      showed a normal weight curve and complete resolution of symptoms. All patients
      showed complete regression of digestive and respiratory symptoms from the first
      examination, with a normal oral meal intake and an improvement of weight and
      height parameters. One case required repeat intervention after 2 years because of
      persisting pain; in this case surgery revealed an insufficient myotomy.
      CONCLUSIONS: Modified extramucosal Heller cardiomyotomy associated with 180
      degree anterior antireflux plastic surgery (according to Thal and Dor's
      procedures) is a useful and safe procedure in the treatment of EA in pediatric
      patients. Our data, which are supported by long-term follow-up, also stress the
      relevance of anterior fundoplication in preventing postoperative gastroesophageal
      reflux.

PMID- 17460492
TI  - Usefulness of ultrasonography in acute appendicitis in early childhood.
AB  - OBJECTIVE: Acute appendicitis is an uncommon diagnosis in early childhood. It is
      frequently complicated by delays in diagnosis, perforation, and prolonged
      hospital stay. The aim of this study was to evaluate the usefulness of
      ultrasonography (US) in the management of suspected appendicitis in children
      younger than 3 years of age. PATIENTS AND METHODS: Seventy-one children under age
      3 with acute abdomen and possible acute appendicitis, but with atypical findings,
      were included. All of the children underwent a US scan to rule out appendicitis.
      RESULTS: There were 41 positive US results for appendicitis. Three children had
      false-positive scan results and 2 children had false-negative results. Twenty
      eight patients had ruptured appendicitis with tumor formation on US. Eighteen of
      the 28 patients received emergency appendectomy and the other 10 patients
      received initial conservative treatment with interval appendectomy. Compared with
      those who received emergency appendectomy, patients who received initial
      conservative treatment had a significantly smoother postoperative course,
      including shorter postoperative hospital stay and earlier postoperative oral
      intake. The overall sensitivity, specificity, accuracy, positive predictive
      value, and negative predictive value of abdominal US to diagnose acute
      appendicitis in cases of atypical findings in early childhood are 95.0%, 90.3%,
      92.9%, 92.6%, and 93.3%, respectively. CONCLUSIONS: US is a useful and highly
      accurate tool to assess acute appendicitis in early childhood. US has the
      potential to aid in diagnosis of early childhood appendicitis to avoid the
      frequent rupture with tumor formation seen at this age. Initial conservative
      treatment for ruptured appendicitis with tumor formation is safe and is
      associated with a smoother postoperative course in early childhood.

PMID- 17460493
TI  - Wilson disease in children: serum aminotransferases and urinary copper on
      triethylene tetramine dihydrochloride (trientine) treatment.
AB  - OBJECTIVES: To evaluate the efficacy of and adherence to trientine and/or zinc
      therapy in children with Wilson disease (WD). MATERIALS AND METHODS: We
      retrospectively reviewed the clinical records of all children with WD in the
      pediatric liver/liver transplant program at our institution between 1998 and
      2006. RESULTS: A total of 22 children with WD were evaluated and treated. Seven
      with fulminant disease required liver transplantation and 15 were treated with
      trientine and/or zinc. Ten of those 15 had follow-up for 12 to 60 months and 6 of
      the latter 10 were followed for 12 to 18 months. All 10 patients were started on
      a trientine treatment regimen. Mean alanine aminotransferase (ALT) levels
      decreased from 183 +/- 103 IU at presentation (n = 10) to 80 +/- 46 IU at 12
      months (n = 10) and 66 +/- 40 IU at 18 months (n = 7). Mean 24-hour urinary
      copper levels increased from 156 microg at presentation to 494 microg at 1 to 2
      months, then decreased to 71 microg after 21 to 24 months of treatment. Three of
      10 patients had normalized ALT levels and 1 patient with cirrhosis continued with
      normal ALT levels since presentation. Four of 10 patients were documented to be
      nonadherent, as manifested by increased ALT levels (99 +/- 31 IU); 1 patient had
      previously normalized ALT levels. In 3 of 10 patients, ALT level decreased but
      remained at an abnormal level (93 +/- 53 IU). CONCLUSIONS: Trientine and/or zinc
      therapy is effective for children with WD. Nonadherence is a common cause of
      increased aminotransferase levels in patients with WD.

PMID- 17460494
TI  - Amplification of bacterial DNA does not distinguish patients with ascitic fluid
      infection from those colonized by bacteria.
AB  - OBJECTIVE: To evaluate 16S ribosomal RNA (rRNA) gene amplification to diagnose
      spontaneous bacterial peritonitis (SBP). PATIENTS AND METHODS: According to a
      retrospective protocol, 31 patients with portal hypertensive ascites (serum to
      ascites albumin gradient > or = 1.1 g/dL) were studied. Ascitic fluid was
      analyzed as follows: Gram stain, aerobic and anaerobic cultures,
      polymorphonuclear cell count, and biochemical tests. Bacterial DNA was detected
      by polymerase chain reaction. RESULTS: There were 8 episodes of SBP and 4
      episodes of bacterascites (BA). Culture was positive in 4 of 8 cases of SBP and
      bacterial DNA was positive in 7 of 8 cases of SBP. Bacterial DNA was positive in
      3 of 4 cases of BA and in 8 of 28 cases of culture-negative non-neutrocytic
      ascites (CNNNA). The PELD score, serum to albumin ascites gradient, and mortality
      showed no statistical difference between patients with CNNNA and the result of
      the bacterial DNA analysis. CONCLUSIONS: Although the 16S rRNA gene amplification
      was better than culture to diagnose SBP, bacterial DNA does not seem to allow a
      distinction between ascites infection and ascites colonization.

PMID- 17460495
TI  - Fasting glucagon-like peptide-1 and its relation to insulin in obese children
      before and after weight loss.
AB  - OBJECTIVE: To study the relationships between glucagon-like peptide-1 (GLP-1),
      weight status, insulin, and insulin resistance in the fasting state. PATIENTS AND
      METHODS: Fasting GLP-1, glucose and insulin concentrations, insulin resistance
      index as homeostasis model assessment (HOMA), body mass index (BMI), and
      percentage body fat based on skinfold thickness measurements were determined in
      42 obese (median age 11 years) and in 16 lean children of the same age. The HOMA
      model was used to calculate degree of insulin resistance. Furthermore, the
      changes in GLP-1, glucose, insulin, and HOMA in the course of 1 year were
      analyzed in the 42 obese children participating in an obesity intervention.
      RESULTS: GLP-1 concentrations did not differ significantly between obese and lean
      children. In multiple linear regression analyses, GLP-1 was significantly related
      to insulin (P = 0.028) and HOMA (P = 0.019) but not to glucose, age, sex,
      pubertal stage, BMI, or percentage body fat. The 15 obese children with
      substantial weight reduction demonstrated significantly (P < 0.05) decreased GLP
      1, insulin, and HOMA levels, whereas these parameters did not change in 27 obese
      children without substantial weight loss. Changes in GLP-1 correlated
      significantly with changes in insulin (r = 0.46, P = 0.001) and HOMA (r = 0.28, P
      = 0.036) but not with changes in glucose, BMI, or percentage of body fat.
      CONCLUSIONS: In children, fasting GLP-1 concentrations are independent of age,
      sex, and pubertal stage. Although GLP-1 did not differ between lean and obese
      children, weight loss was associated with decreasing GLP-1. Inasmuch as GLP-1
      levels were related to insulin concentrations in both cross-sectional and
      longitudinal analyses, we hypothesize a relationship between GLP-1 and insulin in
      the fasting state.

PMID- 17460496
TI  - Impact of diet on the intestinal microbiota in 10-month-old infants.
AB  - OBJECTIVE: To investigate whether diet influences the composition of the
      intestinal microbiota in 10-month-old infants. PATIENTS AND METHODS: Fecal
      samples were collected from sixty-five 10-month-old infants participating in a
      randomized 2 x 2 intervention study comparing cow's milk (CM) with infant formula
      (IF) with or without fish oil (FO) supplement. Infants randomized to CM received
      a daily iron supplement. Bacterial DNA was extracted from the feces. Polymerase
      chain reaction was performed with primers targeting the V3 and V6-8 region of the
      16S rRNA gene and analyzed by denaturing gradient gel electrophoresis (DGGE).
      Cluster analysis of the DGGE gels was performed by use of the Pearson correlation
      coefficient. RESULTS: Samples from infants receiving CM clustered differently
      than did those from the IF group in the V3-based DGGE gels (P < 0.001) and showed
      a different distribution with or without FO in the CM group (P = 0.001) but not
      in the IF group (P = 0.39). Repeat analysis with the V6-8-based DGGE gels showed
      the same pattern, although the V3 gels had 2.5 times as many bands as the V6-8
      gels. CONCLUSIONS: Consumption of CM or IF has a decisive influence on the
      composition of the intestinal microbiota. Supplementation with FO showed an
      effect on the microbiota only in the CM group. We speculate that these
      differences could be influenced by the intake of iron and n-3 polyunsaturated
      fatty acids, respectively.

PMID- 17460497
TI  - Sex-specific responses to zinc supplementation in Nouna, Burkina Faso.
AB  - OBJECTIVES: To study the different responses by sex to zinc supplementation among
      young children. STUDY CHILDREN AND METHODS: Double-blind randomized controlled
      trial of zinc supplementation in 686 children aged 6-30 months, conducted in
      Nouna, a rural area of Burkina Faso. Children received either a 12.5-mg zinc
      sulfate tablet or a placebo every day for about 6 months. Outcomes were
      morbidity, nutritional status, and mortality. RESULTS: Results revealed
      significant differences between boys and girls in their responses to zinc
      supplementation. Boys who received the zinc preparation had fewer days with
      diarrhea than did control boys (RR = 0.88, P = 0.05), especially less nonfebrile
      diarrhea (RR = 0.72, P < 0.001) and less dysentery (RR = 0.65, P = 0.05), but
      more ear infections (RR = 4.00, P < 0.001). By contrast, girls who received the
      zinc supplement had the same prevalence of diarrhea as did control girls, but
      more dysentery (RR = 3.70, P < 0.001), fewer ear infections (RR = 0.39, P <
      0.001), and fewer eye infections (RR = 0.41, P < 0.001). The effect of
      supplementation on nutritional status was not detectable in boys, but girls who
      received supplementation experienced a faster growth velocity in height than did
      control girls (P = 0.004) and a faster growth velocity for weight and height if
      they were wasted and not stunted at baseline (P = 0.003). CONCLUSIONS: Zinc
      supplementation had positive, nil, or negative effects depending on pathological
      condition, and the effects were different for boys than for girls.

PMID- 17460498
TI  - Niacin nutritional status in HIV type 1-positive children: preliminary data.
AB  - OBJECTIVE: HIV infection induces a state of pellagra in cell culture models. This
      study compared the nutritional status and the 24-hour urine excretion of N
      methylnicotinamide between HIV-positive children and HIV-negative children who
      were or were not born of mothers with HIV-1 infection. PATIENTS AND METHODS:
      Forty patients were included in the study: HIV-positive children (group 1; n =
      20), HIV-negative children born to infected mothers (group 2; n = 10), and HIV
      negative control children (group 3; n = 10). Usual dietary intake was assessed by
      a semiquantitative food-frequency questionnaire. Weight and height were assessed
      and compared with the reference data of the U.S. National Center for Health
      Statistics/Centers for Disease Control and Prevention. For the estimation of fat
      free mass and total body water, bioelectrical impedance technique was used. N
      methylnicotinamide was measured by a modified method of high-performance liquid
      chromatography. RESULTS: Groups were matched in relation to age, sex, percentage
      of malnutrition, anthropometric measures, and body composition. Daily niacin
      intake did not differ statistically across groups (group 1 = 18.0 +/- 11.4
      mg/day; group 2 = 18.9 +/- 8.0 mg/day; group 3 = 14.2 +/- 5.2 mg/day), nor did
      intake of tryptophan, vitamin B6, and zinc. The values of urinary niacin per gram
      of creatinine were similar and adequate across the groups (group 1 = 4.68 [0.75
      14.9]; group 2 = 3.74 [1.13-5.69]; group 3 = 3.85 [1.80-8.19]). CONCLUSIONS: HIV
      positive children excreted the same amount of N-methylnicotinamide in urine as
      did the control children. These findings may be attributed to similarities in
      nutritional status, adequate intestinal absorption (no children experienced
      diarrhea) and stable clinical condition.

PMID- 17460499
TI  - Giant cell hepatitis and autoimmune hemolytic anemia successfully treated with
      rituximab.

PMID- 17460500
TI  - Varicella recurrence complicated by pneumonia after liver transplantation for
      APECED.

PMID- 17460501
TI  - Hepatic adenoma in an adolescent with elevated androgen levels.

PMID- 17460502
TI  - Creation of enteral shortcuts as a therapeutic option in children with chronic
      idiopathic intestinal pseudoobstruction.

PMID- 17460503
TI  - Transpyloric feeding in the pediatric intensive care unit.
AB  - The approach to achieving and maintaining nutritional support in pediatric
      intensive care unit patients continues to evolve with newer techniques such as
      transpyloric feeding. We reviewed our transpylorically fed patients over a 4-year
      period and found that we achieved adequate nutritional support in 96% of them. We
      did find an increase in necrotizing enterocolitis in cyanotic patients and
      recommend that these patients be fed with caution when transpyloric feeding is
      used.

PMID- 17460504
TI  - Evaluation of 13C-urea breath test and fecal antigen immunoassay to detect
      Helicobacter pylori infection in Gambian infants.
AB  - Helicobacter pylori colonization was measured by [13C]-urea breath test in 198
      Gambian infants and by fecal enzyme-linked immunosorbent assay in 52 of the 198
      at ages 2, 5, and 12 months. By 12 months there was good concordance between
      tests; 33 of 44 (75%) test results were positive by enzyme-linked immunosorbent
      assay, and 29 of 44 (66%) test results were positive by urea breath test. H.
      pylori colonization is common among Gambian infants, and noninvasive tests can
      provide a reliable means of diagnosis.

PMID- 17460505
TI  - Differentiating ulcerative colitis from Crohn disease in children and young
      adults: report of a working group of the North American Society for Pediatric
      Gastroenterology, Hepatology, and Nutrition and the Crohn's and Colitis
      Foundation of America.
AB  - BACKGROUND: Studies of pediatric inflammatory bowel disease (IBD) have varied in
      the criteria used to classify patients as having Crohn disease (CD), ulcerative
      colitis (UC), or indeterminate colitis (IC). Patients undergoing an initial
      evaluation for IBD will often undergo a series of diagnostic tests, including
      barium upper gastrointestinal series with small bowel follow-through, abdominal
      CT, upper endoscopy, and colonoscopy with biopsies. Other tests performed less
      frequently include magnetic resonance imaging scans, serological testing, and
      capsule endoscopy. The large amount of clinical information obtained may make a
      physician uncertain as to whether to label a patient as having CD or UC.
      Nevertheless, to facilitate the conduct of epidemiological studies in children,
      to allow the entry of children into clinical trials, and to allow physicians to
      more clearly discuss diagnosis with their patients, it is important that
      clinicians be able to differentiate between CD and UC. METHODS: A consensus
      conference regarding the diagnosis and classification of pediatric IBD was
      organized by the Crohn's and Colitis Foundation of America. The meeting included
      10 pediatric gastroenterologists and 4 pediatric pathologists. The primary aim
      was to determine the utility of endoscopy and histology in establishing the
      diagnosis of CD and UC. Each member of the group was assigned a topic for review.
      Topics evaluated included differentiating inflammatory bowel disease from acute
      self-limited colitis, endoscopic and histological features that allow
      differentiation between CD and UC, upper endoscopic features seen in both CD and
      UC, ileal inflammation and "backwash ileitis" in UC, patchiness and rectal
      sparing in pediatric IBD, periappendiceal inflammation in CD and UC, and
      definitions of IC. RESULTS: Patients with UC may have histological features such
      as microscopic inflammation of the ileum, histological gastritis, periappendiceal
      inflammation, patchiness, and relative rectal sparing at the time of diagnosis.
      These findings should not prompt the clinician to change the diagnosis from UC to
      CD. Other endoscopic findings, such as macroscopic cobblestoning, segmental
      colitis, ileal stenosis and ulceration, perianal disease, and multiple granulomas
      in the small bowel or colon more strongly suggest a diagnosis of CD. An algorithm
      is provided to enable the clinician to differentiate more reliably between these
      2 entities. CONCLUSIONS: The recommendations and algorithm presented here aim to
      assist the clinician in differentiating childhood UC from CD. We hope the
      recommendations in this report will reduce variability among practitioners in how
      they use the terms "ulcerative colitis," "Crohn disease," and "indeterminate
      colitis." The authors hope that progress being made in genetic, serological, and
      imaging studies leads to more reliable phenotyping.

PMID- 17460507
TI  - Ruptured proximal lenticulostriate artery fusiform aneurysm presenting with
      subarachnoid hemorrhage: case report.
AB  - OBJECTIVE: Lenticulostriate artery aneurysms are rare. When present, distal
      locations in and around the basal ganglia are more common and often present with
      intraparenchymal hemorrhage when ruptured. We present a very rare case of a
      ruptured proximal lenticulostriate fusiform aneurysm presenting with subarachnoid
      hemorrhage. CLINICAL PRESENTATION: We report the case of a 31-year-old healthy
      man who presented after the sudden onset of headache, nausea, and lethargy
      without neurological deficits. Cranial computed tomographic scanning demonstrated
      diffuse subarachnoid hemorrhage, and a cranial computed tomographic angiogram
      demonstrated a vascular irregularity on the superior surface of the left distal
      M1 trunk of the middle cerebral artery. A cerebral angiogram demonstrated a left
      proximal lenticulostriate fusiform aneurysm without evidence of moyamoya-like
      vessels or vasculitis. No other pathology or infectious etiology was noted.
      INTERVENTION: Endovascular therapy was deemed unsafe, and microsurgical
      exploration and intervention was the more favorable and safe approach. A standard
      left pterional craniotomy was performed and the afferent lenticulostriate vessel
      into the fusiform aneurysm was visualized. Temporary clips were applied to the
      proximal and distal M1 trunk and miniclips were applied across the afferent
      portion and fundus of the aneurysm, thus sacrificing the parent lenticulostriate
      artery. A postoperative computed tomographic scan demonstrated an area of
      hypodensity in the left basal ganglia. The patient's postoperative right facial
      and upper extremity weakness improved to normal several days after aneurysmal
      clipping. CONCLUSION: This is the first report of a ruptured proximal
      lenticulostriate artery fusiform aneurysm, which presented as subarachnoid
      hemorrhage in a healthy patient without an underlying vascular disease.

PMID- 17460508
TI  - Thrombosis of a fusiform intracranial aneurysm induced by overlapping neuroform
      stents: case report.
AB  - OBJECTIVE: To present a case of a true fusiform basilar artery aneurysm that
      underwent spontaneous thrombosis after placement of two overlapping Neuroform
      stents (Boston Scientific/Target, Fremont, CA). CLINICAL PRESENTATION: A 45-year
      old woman with transient syncopal episodes experienced a fall and presented to
      the emergency room. Incidentally, a non-contrast head computed tomographic scan
      and digital subtraction angiography demonstrated an unruptured, fusiform mid
      basilar artery aneurysm. INTERVENTION: Endovascular treatment was initiated by
      using a stent-assisted coil embolization technique with placement of a self
      expanding, dedicated intracranial, Neuroform stent in the basilar artery across
      the aneurysm's fusiform neck. Attempts to access the aneurysm for coil
      embolization resulted in transient migration of the stent into the aneurysm sac.
      A second Neuroform stent was advanced in telescoping fashion for salvage and
      stable coverage across the entire aneurysm; therefore, coil embolization was
      deferred to allow stent endothelialization. After 6 weeks on dual antiplatelet
      therapy, the patient presented with transient ischemic symptoms suggesting top of
      the basilar artery syndrome. Subsequent magnetic resonance imaging scans and
      angiography indicated circumferential thrombus formation in the aneurysm sac but
      patent flow in the basilar artery. A computed tomographic scan at 6 months and
      digital subtraction angiography at 12 months confirmed complete thrombosis of the
      fusiform mid-basilar artery aneurysm with basilar artery reconstruction.
      CONCLUSION: Overlapping Neuroform stents may induce spontaneous thrombosis of
      intracranial aneurysms and facilitate parent artery reconstruction through flow
      remodeling and stent endothelialization. Double stent placement may be a viable
      option in dissecting or fusiform intracranial aneurysms that are not amenable to
      open surgical treatment or endovascular coil embolization.

PMID- 17460509
TI  - Cavernous hemangioma of the cavernous sinus, skin, and retina: hemodynamic
      changes after treatment: case report.
AB  - OBJECTIVE: There are several reports concerning cavernous hemangiomas of the skin
      and central nervous system. Additional retinal involvement has also been
      reported. CLINICAL PRESENTATION: The authors report a 69-year-old woman with a
      giant extra-axial cavernous hemangioma of the right cavernous sinus involving the
      supra- and parasellar region, retina, and skin. INTERVENTION: Shrinkage of its
      cutaneous part lead to subsequent increase of the volume of the intracranial
      part. Owing to compression of the optic and the oculomotor nerves, oculomotor
      disturbances, ptosis, and visual impairment to 0.2 occurred. Via a pterional
      approach microsurgical removal of the tumor except for a remnant of the
      intracavernous part was performed. CONCLUSION: Hemodynamic connection between
      cutaneous, retinal, and intracranial hemangiomas should be considered.

PMID- 17460510
TI  - Papillary tumors of the pineal region: case report.
AB  - OBJECTIVE: The pineal region is a rare intracranial site for metastasis. We
      report three patients initially considered to have metastatic papillary
      adenocarcinoma to the pineal region. On review, these papillary, keratin-positive
      neoplasms meet the criteria for papillary tumor of the pineal region (PTPR).
      CLINICAL PRESENTATION: These neoplasms occurred in three women (age range, 37-55
      yr). Imaging studies demonstrated well-circumscribed lesions in the pineal
      region. All patients presented with obstructive hydrocephalus and symptoms
      attributable to hydrocephalus and tectal compression. INTERVENTION: All three
      patients underwent near total microsurgical resection of the pineal region
      neoplasm, followed by adjuvant radiotherapy. The two patients with long-term
      follow-up (56-60 mo) have remained clinically stable without evidence of local or
      distant recurrence. The first two patients were initially diagnosed as having
      papillary metastatic carcinoma of unknown origin. The third patient was treated
      after the recent description of PTPR and met the histopathological diagnostic
      criteria. Retrospective pathological review of the previous two patients resulted
      in designation as PTPR. CONCLUSION: The morphological features of the tumors in
      our series, along with the clinical presentations, are similar to those in the
      original description of the PTPR. Our findings agree with the original hypothesis
      that the cells composing the PTPR are similar to ependymal cells of the
      subcommissural organ, thus furthering the hypothesis that the PTPR derives from a
      specialized ependymocyte associated with the subcommissural organ. The two
      patients with long-term follow-up (56-60 mo) have remained clinically stable
      without evidence of local or distant recurrence.

PMID- 17460511
TI  - Recurrent carpal tunnel syndrome owing to an implantation epidermoid cyst after
      carpal tunnel decompression: case report.
AB  - OBJECTIVE: Implantation epidermoid cysts have been reported after a variety of
      surgical procedures. Although carpal tunnel surgery is the most common peripheral
      nerve operation, there have been no previous reports of these cysts after carpal
      tunnel decompression. We present a case of an implantation epidermoid cyst after
      carpal tunnel surgery. CLINICAL PRESENTATION: A 41-year-old man presented with
      recurrence of carpal tunnel syndrome and an enlarging mass at the site of his
      previous carpal tunnel decompression. INTERVENTION: The operation site was re
      explored, and a subcutaneous mass was removed. This was histologically shown to
      be an implantation epidermoid cyst. CONCLUSION: The possibility of an implanted
      epidermoid cyst should be considered in any patient who presents with a
      recurrence of carpal tunnel symptoms and a mass at the site of the previous
      operation. It is possible that the occurrence of these cysts may be related to
      the use of polyglactin sutures for wound closure. In this case, the result of
      surgery was excellent.

PMID- 17460514
TI  - Molecular genetics of meningiomas: from basic research to potential clinical
      applications.
AB  - To review our current understanding of the molecular pathogenesis of meningiomas,
      to suggest topics for future investigations, and to present perspectives for
      clinical application. Significant progress has been made in recent years in
      delineating the molecular mechanisms involved in meningioma formation, growth,
      and malignant progression. However, many questions remain unanswered. Mutations
      in the NF2 gene probably account for the formation of more than half of all
      meningiomas. On the other hand, the molecular events underlying the initiation of
      meningiomas without NF2 mutations have yet to be identified. Investigating
      hereditary conditions associated with an increased meningioma incidence and the
      mechanisms underlying the development of radiation-induced meningiomas could
      potentially yield relevant insights. Meningioma growth is sustained by the
      dysregulated expression of steroid hormones, growth factors, their receptors, and
      activation of signal transduction cascades. The underlying genetic causes are
      unknown. Malignant progression of meningiomas probably involves the inactivation
      of tumor suppressor genes on chromosomes 1p, 9p, 10q, and 14q. However, with the
      possible exception of INK4A/INK4B, the actual targets of these chromosomal losses
      have remained largely elusive. Cell cycle dysregulation and telomerase activation
      have been recognized as important steps in meningioma progression. Telomere
      dynamics, cell cycle control, and the mechanisms responsible for deoxyribonucleic
      acid damage control are tightly interwoven. Investigating genes involved in the
      maintenance of genomic integrity might significantly deepen the understanding of
      meningioma progression. An area that has received relatively little attention
      thus far is the genetic background of meningioma spread and invasion. Possible
      clinical applications of the molecular data available may include a meningioma
      grading system based on genetic alterations, as well as therapeutic strategies
      for refractory meningiomas aimed at interfering with signal transduction
      pathways.

PMID- 17460515
TI  - Stereotactic radiosurgery: adjacent tissue injury and response after high-dose
      single fraction radiation. Part II: Strategies for therapeutic enhancement, brain
      injury mitigation, and brain injury repair.
AB  - In the first part of this series, we reviewed the histological, radiographic, and
      molecular data gathered regarding the brain parenchymal response to radiosurgery
      and suggested future studies that could enhance our understanding of the topic.
      With this article, we begin by addressing methods of potentiating the effect of
      radiosurgery on target lesions of the central nervous system. Much of the work on
      potentiating the effects of cranial radiation has been performed in the field of
      whole-brain radiotherapy. Data from Phase III trials evaluating the efficacy of
      various agents as radiosensitizers or radioenhancers in whole-brain radiotherapy
      are reviewed, and trials for investigating certain agents as enhancers of
      radiosurgery are suggested. The roles of gene therapy and nanotechnology in
      enhancing the therapeutic efficacy of radiosurgery are then addressed. Focus is
      then shifted to a discussion of strategies of protecting healthy tissue from the
      potentially deleterious aspects of the brain's response to radiosurgery that were
      presented in the first article of this series. Finally, comments are made
      regarding the role of neural progenitor or stem cells in the repair of radiation
      induced brain injury after radiosurgery. The importance of both the role of the
      extracellular matrix and properly directed axonal regrowth leading to appropriate
      target reinnervation is highlighted.

PMID- 17460516
TI  - Deep hypothermic circulatory arrest for complex cerebral aneurysms: lessons
      learned.
AB  - OBJECTIVE: Deep hypothermic circulatory arrest is a useful adjunct for treating
      complex aneurysms. Decreased cerebral metabolism and resultant ischemic tolerance
      create an environment suitable for devascularizing high-risk lesions. However,
      the advent of modern imaging modalities, innovative cerebral revascularization
      strategies, and the emergence of endovascular stenting and coiling limit the
      number of aneurysms requiring this surgical intervention. We present 66 patients
      with intracranial aneurysms who underwent surgical clipping under deep
      hypothermic arrest and attempt to identify patients well-suited for this
      procedure. METHODS: This study was conducted during a 15-year period and examined
      patients with aneurysms of the anterior and posterior cerebral circulation.
      Demographics, aneurysm characteristics, and surgical factors were evaluated as
      predictors of functional outcome. RESULTS: Patient age and the duration of
      cardiac arrest were independent predictors of early clinical outcome (P < 0.05).
      Our experience suggests that the ideal patient is younger than 60 years old and
      harbors few medical comorbidities. Individuals with large aneurysms of the
      anterior communicating artery, internal carotid artery bifurcation, posterior
      inferior cerebellar artery, midbasilar, or vertebral arteries and with an absence
      of thrombosis and calcium may be most likely to experience favorable outcomes.
      Circulatory arrest should not exceed 30 minutes. Postoperative computed
      tomographic scanning and timely anesthetic emergence allow for early detection of
      hemorrhage. Complete dissection of the aneurysm before bypass and avoiding
      extreme hypothermia yield a low incidence of life-threatening postoperative
      hematomas. CONCLUSION: Hypothermic circulatory arrest is a useful technique for
      neuroprotection during the clipping of complex cerebral aneurysms. This
      procedure, however, has several associated risks. Patient factors, pathoanatomic
      characteristics, and surgical parameters may be used to guide patient selection.

PMID- 17460517
TI  - Analysis of intrathecal interleukin-6 as a potential predictive factor for
      vasospasm in subarachnoid hemorrhage.
AB  - OBJECTIVE: Inflammatory response seems to be one of the relevant
      pathophysiological aspects for developing vasospasm in subarachnoid hemorrhage.
      The probable diagnostic value of intrathecal proinflammatory markers is still
      unclear and is assessed in this study. METHODS: We analyzed daily clinical data
      and laboratory tests of the cerebrospinal fluid (CSF) of 64 patients with mostly
      poor-grade subarachnoid hemorrhage during a period of 14 days. Special attention
      was given to the relationship between the development of vasospasm and the time
      course of the intrathecal interleukin (IL)-6 concentrations in CSF (IL-6CSF). The
      potential power of IL-6CSF for predicting vasospasm was studied. RESULTS:
      Vasospasm developed in 28.1% of the patients, with a mean onset of 6.4 days after
      bleeding, and was detected by conventional methods. Patients with vasospasm
      demonstrated statistically significant higher median values of IL-6CSF on Days 4
      and 5 (P < 0.05). Most importantly, the increase of IL-6CSF preceded the
      conventional signs of vasospasm. A cut-off value of IL-6CSF of at least 2000
      pg/ml on Day 4 yielded an 11.72-fold higher relative risk (95% confidence
      interval, 2.93-46.60) of developing vasospasm, predicting vasospasm with a
      sensitivity of 88.9% and a specificity of 78.3%. We found a statistically
      significant correlation between IL-6CSF and delayed cerebral ischemia for Day 7
      (P = 0.03). However, there was no correlation with IL-6CSF on any other day and
      outcome. CONCLUSION: IL-6CSF seems to be a reliable early marker for predicting
      vasospasm after subarachnoid hemorrhage on Days 4 and 5 before clinical onset.

PMID- 17460518
TI  - The role of race in time to treatment after subarachnoid hemorrhage.
AB  - OBJECTIVE: Blacks have higher mortality rates from aneurysmal subarachnoid
      hemorrhage (SAH) than Caucasians. The time to treatment for aneurysmal SAH has
      been found to correlate with mortality and outcome. Therefore, we examined racial
      differences in the time to treatment of aneurysmal SAH among patients from the
      Greater Cincinnati area. METHODS: We evaluated data from 439 adult aneurysmal SAH
      patients prospectively identified from May 1997 to August 2001 and July 2002 to
      March 2005. The primary outcome measure was time to treatment, defined as elapsed
      time from arrival in the emergency department to aneurysm treatment. A
      multivariable model was constructed to determine the role of potential variables,
      including race, on time to treatment for SAH. RESULTS: In univariate analysis,
      Caucasian patients were significantly older than black patients (P < 0.0001) and
      were more likely to be male (P = 0.014), insured (P < 0.0001), and transferred
      from emergency departments of presentation to other hospitals (P < 0.0001). Black
      patients were more likely to have anterior circulation aneurysms (P = 0.009) and
      preexisting hypertension (P < 0.001). In univariate analysis, anterior
      circulation aneurysms showed a trend toward earlier treatment than posterior
      circulation aneurysms (P = 0.07). In multivariable models, race was not
      associated with time to treatment or case-fatality rate. Patients transferred
      from other facilities were treated more expeditiously than patients who presented
      directly to the emergency department (P = 0.003), and a history of diabetes
      mellitus was associated with delay in treatment (P = 0.05). CONCLUSION: Race was
      not associated with time to treatment after aneurysmal SAH in the Greater
      Cincinnati area. Reducing the increased burden of SAH mortality among blacks must
      be addressed at the prevention stage.

PMID- 17460519
TI  - Olfactory groove meningiomas: clinical outcome and recurrence rates after tumor
      removal through the frontolateral and bifrontal approach.
AB  - OBJECTIVE: Olfactory groove meningiomas account for 8 to 13% of all intracranial
      meningiomas. Surgical removal is often performed through the bifrontal,
      unilateral subfrontal (frontolateral), or pterional approach. We report on the
      clinical outcome and recurrence rate after surgical treatment of olfactory groove
      meningiomas in our neurosurgical department. METHODS: A retrospective study was
      conducted by analyzing the charts of the patients, including surgical records,
      discharge letters, histological records, follow-up records, and imaging studies.
      RESULTS: A total of 1800 meningiomas were operated on between 1978 and 2002 in
      our department. There were 82 patients with olfactory groove meningiomas,
      including 63 women and 19 men with a mean age of 57.8 years (age range, 33-91
      yr). Most patients presented with mental disturbance. Tumors were operated
      through the bifrontal (n = 46), frontolateral (n = 34), and pterional (n = 2)
      approaches. Total tumor removal (Simpson Grade 1 or 2) was achieved in most cases
      (91.2% frontolateral, 93.5% bifrontal). Perioperative mortality was 4.9% (four
      out of 82 patients, all operated through the bifrontal approach). The overall
      recurrence rate was 4.9%, with four patients requiring surgery. The mean follow
      up period was 63.4 months (range, 4-270 mo). CONCLUSION: Olfactory groove
      meningiomas were removed mainly through two different surgical approaches. Even
      in large tumors, high rates of total tumor resection could also be achieved with
      low recurrence rates using the simple and minimally invasive frontolateral
      approach. In recent years, we have preferred to use the frontolateral approach,
      which provides quick access to the tumor with less brain exposure while still
      enabling total tumor removal with a low morbidity rate and no mortality.

PMID- 17460520
TI  - Gamma knife surgery for facial nerve schwannomas.
AB  - OBJECTIVE: Radical resection of facial nerve schwannomas classically implies a
      high risk of severe facial palsy. Owing to the rarity of facial palsy after gamma
      knife surgery (GKS) of vestibular schwannomas, functional evaluation after GKS
      seems rational in this specific group of patients. To our knowledge, no previous
      similar evaluation exists in the literature. METHODS: Of 1783 schwannomas of the
      cerebellopontine angles treated by GKS at Timone University Hospital between July
      1992 and May 2003, 11 were diagnosed as originating from the facial nerve.
      Criteria for this diagnosis were the involvement of the tympanic or mastoid
      segment of the facial nerve (n = 9) and/or preoperative observation of a facial
      nerve deficit that had occurred during previous microsurgery (two patients). The
      rare occurrence of facial palsy after vestibular schwannoma radiosurgery, usually
      within 18 months of treatment, has been considered only in the patients with more
      than 2 years of follow-up (n = 9). RESULTS: Six of these patients experienced a
      previous spontaneous facial palsy on one (n = 4) or several occasions (n = 2). A
      normal motor facial function was observed in only three patients before GKS
      (House-Brackmann Grade II in six patients, Grade III in one patient, Grade IV in
      one patient). The median follow-up period was 39 months (range, 18-84 mo). At the
      time of the last follow-up examination, no patients had developed a new facial
      palsy or experienced deterioration of a preexisting facial palsy and three
      patients had improvement of a preoperative facial palsy. Ten out of the 11 tumors
      are stable or decreased in size; in the other, a microsurgical resection of the
      tumor had been recommended owing to the development of a cyst. Clinical
      management owing to the specificity and heterogeneity of this group of patients
      has required the development of an original classification of four anatomic
      subtypes presenting different clinical and surgical difficulties. CONCLUSION:
      This first study demonstrates that radiosurgery allows treatment of these
      patients while preserving normal motor facial function. Such an advantage should
      lead to the consideration of GKS as a first treatment option for small- to medium
      size facial nerve schwannomas.

PMID- 17460521
TI  - Safety of radiosurgery applied to conditions with abnormal tumor suppressor
      genes.
AB  - OBJECTIVE: To assess the risk of radiosurgery inducing malignancy in
      neurofibromatosis-2 (NF2) and von Hippel-Lindau disease. METHODS: A retrospective
      cohort study of 118 NF2 and 19 von Hippel-Lindau disease patients, totalling 906
      and 62 patient-years of follow-up data, respectively. RESULTS: Two cases of
      intracranial malignancy were identified, both of which occurred in NF2 patients.
      One of these was thought to have arisen before the radiosurgery; the other was a
      glioblastoma diagnosed 3 years after radiosurgery. CONCLUSION: Because gliomas
      may occur in as many as 4% of NF2 patients, this may not represent an increased
      risk. We continue to offer radiosurgery treatment to selected NF2 and von Hippel
      Lindau disease patients and consider that the late risk of malignancy arising
      after irradiation must be put in the context of the condition being treated, the
      treatment options available to these individuals, and their life expectancy.

PMID- 17460522
TI  - The natural history of conservatively managed symptomatic intramedullary spinal
      cord cavernomas.
AB  - OBJECTIVE: The presentation and natural history of untreated, symptomatic
      intramedullary spinal cavernomas at our institution were analyzed. The objective
      is to provide additional information regarding the natural history of
      conservatively managed, symptomatic, intramedullary spinal cord cavernous
      malformations. METHODS: The medical records of patients treated in our
      institution between 1989 and 2002 were reviewed to identify those with
      intramedullary cavernomas. The medical, radiological, surgical, and pathological
      records from these patients were retrospectively reviewed and analyzed. RESULTS:
      Fourteen patients were included in the study. The mean age at presentation was 42
      years. Four lesions (29%) were located in the cervical region and 10 lesions
      (71%) were present in the thoracolumbar spinal cord. All patients were
      symptomatic at the time of presentation. In this cohort of 14 patients, 10
      patients (71%) were conservatively managed. For these patients, the mean duration
      of symptoms before presentation was 10 months. The mean duration of follow-up
      from the time of presentation was 80 months. The median McCormick grade for
      conservatively treated patients at presentation was II. During this period, none
      of the conservatively managed patients had an acute intramedullary bleed. In nine
      patients, the McCormick grade at the last follow-up evaluation was the same as or
      better than their score at presentation. Four patients (29%) were treated
      surgically. The mean duration of symptoms before presentation was 33 months. The
      mean duration of follow-up from the time of presentation was 42 months. In two
      surgical patients, the McCormick grade at the last follow-up evaluation remained
      unchanged compared with their score at presentation, whereas the McCormick grade
      improved in one patient and deteriorated in another patient. CONCLUSION: This
      cohort of conservatively managed patients with symptomatic, intramedullary spinal
      cord cavernomas was clinically stable throughout the follow-up period. In this
      series, patients harboring symptomatic spinal cord cavernous malformation did not
      have significant, permanent neurological decline during the follow-up period when
      treated with the conservative approach of observation. This data provides
      additional information for determining the appropriate treatment strategy for
      patients with intramedullary spinal cavernomas.

PMID- 17460523
TI  - Long-term seizure outcome in reoperation after failure of epilepsy surgery.
AB  - OBJECTIVE: Treatment of patients who fail epilepsy surgery is problematic.
      Selected patients may be candidates for further surgery, potentially leading to a
      significant decrease in the frequency and severity of seizures. We present our
      long-term outcome series of highly investigated patients who failed resective
      epilepsy surgery and subsequently underwent reoperative resective procedures.
      METHODS: We performed a retrospective consecutive analysis of patients who
      underwent reoperative procedures because of medically intractable epilepsy at our
      institution from 1990 to 2001. Seventy patients underwent reoperative epilepsy
      surgery, with 57 patients having a minimum follow-up period of 2 years. We
      assessed the relationship between seizure outcome and categorical variables using
      chi2 and Fisher's exact tests, and the relationship between outcome and
      continuous variables using a Wilcoxon rank-sum test. Statistical significance was
      set at a P value of 0.05. RESULTS: Of the 57 patients (29 male and 28 female
      patients), the age of seizure onset ranged from 3 months to 39 years (mean, 10.7
      +/- 10.3 yr; median, 7 yr). The mean age at reoperation was 24.7 +/- 12 years
      (range, 4-50 yr). The interval between first and second resection was 7 days to
      16 years. The follow-up period ranged from 24 to 228 months (mean, 128 mo; mode,
      132 mo). Seizure outcome was classified according to Engel's classification.
      Fifty-two percent of the patients had a favorable outcome (38.6% were Class I and
      14.0% were Class II). Patients with tumors as their initial pathology had better
      outcome compared with patients with focal cortical dysplasia and mesial temporal
      sclerosis (P < 0.05). CONCLUSION: Reoperation should be considered in selected
      patients failing epilepsy resective surgery because approximately 50% of patients
      may have benefit. Patients with cortical dysplasia and mesial temporal sclerosis
      are less likely to improve after reoperation.

PMID- 17460524
TI  - Efficacy of prophylactic antibiotics against meningitis after craniotomy: a meta
      analysis.
AB  - OBJECTIVE: Although prophylactic antibiotics have been shown by randomized
      clinical trials (RCTs) to help prevent deep infection after craniotomies, recent
      reports have suggested that antibiotics are not effective in preventing
      postcraniotomy meningitis. METHODS: Data on meningitis as an end point from RCTs
      on prophylactic antibiotics for craniotomies were pooled in a random-effects meta
      analysis. RESULTS: Six prospective randomized trials or trial subgroups enrolling
      1729 patients or operations were identified. Antibiotics reduced postoperative
      infection rates in five of the six RCTs; no trial individually showed a
      statistically significant benefit from antibiotics. The pooled odds ratio for
      meningitis with antibiotic treatment in the six RCTs was 0.43 (95% confidence
      interval, 0.20-0.92; P = 0.03). Subgroup analyses showed no detectable difference
      in antibiotic efficacy if antibiotics, with or without gram- negative coverage,
      were used or if the trial was single or double blinded. A sensitivity analysis
      showed modest dependence of the results of the analysis on the specific
      definition of postoperative meningitis used in interpreting trial results.
      CONCLUSION: Prophylactic antibiotics administered before craniotomy reduce rates
      of postoperative meningitis by approximately one-half, a statistically and
      clinically significant benefit.

PMID- 17460525
TI  - Gangliocytoma of the spinal cord.

PMID- 17460526
TI  - Construction of a three-dimensional interactive model of the skull base and
      cranial nerves.
AB  - OBJECTIVE: The goal was to develop an interactive three-dimensional (3-D)
      computerized anatomic model of the skull base for teaching microneurosurgical
      anatomy and for operative planning. METHODS: The 3-D model was constructed using
      commercially available software (Maya 6.0 Unlimited; Alias Systems Corp.,
      Delaware, MD), a personal computer, four cranial specimens, and six dry bones.
      Photographs from at least two angles of the superior and lateral views were
      imported to the 3-D software. Many photographs were needed to produce the model
      in anatomically complex areas. Careful dissection was needed to expose important
      structures in the two views. Landmarks, including foramen, bone, and dura mater,
      were used as reference points. RESULTS: The 3-D model of the skull base and
      related structures was constructed using more than 300,000 remodeled polygons.
      The model can be viewed from any angle. It can be rotated 360 degrees in any
      plane using any structure as the focal point of rotation. The model can be
      reduced or enlarged using the zoom function. Variable transparencies could be
      assigned to any structures so that the structures at any level can be seen.
      Anatomic labels can be attached to the structures in the 3-D model for
      educational purposes. CONCLUSION: This computer-generated 3-D model can be
      observed and studied repeatedly without the time limitations and stresses imposed
      by surgery. This model may offer the potential to create interactive surgical
      exercises useful in evaluating multiple surgical routes to specific target areas
      in the skull base.

PMID- 17460527
TI  - A means for targeting therapeutics to peripheral nervous system neurons with
      axonal damage.
AB  - OBJECTIVE: Delivery of biological therapeutics to motor and dorsal root ganglion
      neurons remains a major hurdle in the development of treatments for a variety of
      neurological processes, including peripheral nerve injury, pain, and motor neuron
      diseases. Because nerve cell bodies are important in initiating and controlling
      axonal regeneration, targeted delivery is an appealing strategy to deliver
      therapeutic proteins after peripheral nerve injury. METHODS: Tet1 is a 12-aa
      peptide, isolated through phage display that is selected for tetanus toxin C
      fragment-like binding properties. In this study, we surveyed its uptake and
      retrograde transport using compartmented cultures and sciatic nerve injections.
      We then characterized the time course of this delivery. Finally, to confirm the
      retrograde transport involvement, a colchicine pretreatment was performed. We
      also performed competitive binding studies between Tet1 and a recombinant tetanus
      toxin C fragment using recombinant tetanus toxin C fragment enzyme-linked
      immunosorbent assay. RESULTS: We were able to demonstrate efficient uptake and
      retrograde axonal transport of the Tet1 peptide in vitro and in vivo. Intraneural
      colchicine pretreatment partially blocked fluorescence detection in the spinal
      cord, revealing a retrograde axonal transport mechanism. Finally, a competitive
      enzyme-linked immunosorbent assay experiment revealed Tet1-specific binding to
      the recombinant tetanus toxin C fragment axon terminal trisialogangliosides
      receptor. CONCLUSION: These properties of Tet1 can be applied to the development
      of therapeutic viral vectors and fusion proteins for neuronal targeting and
      enhanced spinal cord delivery in the treatment of nerve regeneration,
      neuroprotection, analgesia, and spasticity. Small peptides can be easily fused to
      larger proteins without significantly modifying their function and can be used to
      alter the binding and uptake properties of these proteins.

PMID- 17460528
TI  - Deafferentation pain resulting from cervical posterior rhizotomy is alleviated by
      chromaffin cell transplants into the rat spinal subarachnoid space.
AB  - OBJECTIVE: Deafferentation pain is common after posttraumatic brachial plexus
      avulsion in humans. Alleviation of such pain is poorly achieved by most
      therapeutic interventions; the only efficient neurosurgical procedure currently
      available is lesioning of the dorsal root entry zone. Previous work has
      demonstrated that adrenal medullary transplants into the lumbar spinal
      subarachnoid space can alleviate neuropathic pain behavior resulting from
      peripheral nerve or spinal cord injury. The purpose of this study was to evaluate
      the potential effects of adrenal medullary transplants on brachial plexus
      deafferentation pain. METHODS: The cervical posterior rhizotomy model was
      selected as an upper segmental deafferentation model because it mimics the
      pathological situation after traumatic brachial plexus avulsion in humans.
      Animals underwent a right posterior cervical rhizotomy extending from C5 to T1
      and received either adrenal medullary transplants or control striated muscle
      transplants into the cervical subarachnoid space. The clinical evolution was
      evaluated daily for self-directed behaviors indicative of ongoing pain, including
      onset, dermatomal extent, and severity. RESULTS: In animals with muscle control
      transplants, self-directed behaviors appeared in 83.3% of the group, with a mean
      delay between rhizotomy and onset of self-directed behaviors of 8 days. In
      contrast, only 30.8% of the animals implanted with chromaffin cells exhibited any
      signs of self-directed behaviors, and these had a mean onset delay of 14 days.
      CONCLUSION: The suppression of self-directed behaviors by adrenal medullary
      transplants is similar to that observed after dorsal root entry zone lesioning
      and suggests that this approach may offer a nonablative alternative in the
      management of deafferentation pain resulting from dorsal root avulsion.

PMID- 17460529
TI  - Intrathecal epidermal growth factor and fibroblast growth factor-2 exacerbate
      meningeal proliferative lesions associated with intrathecal catheters.
AB  - OBJECTIVE: There is evidence that promoting the proliferation of endogenous
      neural stem cells in the spinal cord could be an effective strategy in the
      treatment of spinal cord injury. We studied this proliferation in a minimal
      injury rat model in the presence of epidermal growth factor and fibroblast growth
      factor-2. METHODS: Adult female Sprague Dawley rats were minimally injured at T8
      and received the growth factors intrathecally by osmotic pump for either 3, 7, or
      14 days beginning immediately after spinal cord injury. The infusions were made
      through a subarachnoid catheter connected to an osmotic minipump. Beginning at
      the time of injury, the rats received daily bromodeoxyuridine to label
      proliferating cells for determination of the labeling index. RESULTS: Significant
      differences were found in the labeling index between injured and non-injured
      rats. We concluded that minimal spinal cord injury from the stab injury and from
      the catheter itself increased the proliferation of ependymal region
      stem/progenitor cells. A minority (23.3%) of the rats developed proliferative
      lesions in association with the catheters alone, but the lesions were
      significantly larger and occurred in almost all (93.8%) rats receiving the
      mitogens, resulting in marked spinal cord compression. CONCLUSION: The large
      proliferative growths in the epidermal growth factor and fibroblast growth factor
      2-treated rats were unexpected and are indicative of the major effects of these
      mitogens. This suggests that considerable caution is required in devising
      therapeutic strategies directed toward mitogenic stimulation by growth factors
      delivered into the subarachnoid space. Further study is required to determine the
      appropriate and safe dosage of mitogens for potential use in spinal cord repair.

PMID- 17460530
TI  - Predictors of neurosurgical career choice among residents and residency
      applicants.
AB  - OBJECTIVE: Medical students applying for neurosurgery residency positions almost
      all aspire to become academic neurosurgeons. However, most graduates of
      neurosurgery residency programs ultimately follow careers in private practice. We
      hypothesized that there might be factors in a resident's application, interviews,
      or performance during residency that might predict this change in career
      orientation. METHODS: We retrospectively reviewed the applications, interview
      evaluations, and residency performance reviews of graduates from the Neurological
      Surgery program at the University of California, San Francisco and examined
      factors that might correlate with their career choices. RESULTS: Between 1968 and
      2003, 69 neurosurgical residents graduated from the residency program. Of the 54
      respondents (78%), 25 (46%) held academic positions and 29 (54%) were in private
      practice. None of the application data correlated with career choice, and no
      significant differences in interview scores were observed between academic and
      private practitioners. Board scores, publications, presentations, and awards
      received during residency were not predictive of practice orientation. Favorable
      evaluations during the junior (P = 0.04) and chief residency (P = 0.03) years and
      pursuit of a subspecialty fellowship (P = 0.006) were predictive. CONCLUSION:
      Honest discussion between residents and faculty about the choice between academic
      and private practice careers may be as informative as the three identified
      predictors of residents' career orientation. Academic faculty members can
      encourage communication by discouraging the perception that a resident's
      education might be compromised if he or she expresses interest in private
      practice rather than academic neurosurgery. Open communication on this issue
      might enable faculty mentors to actively advise residents in their career
      decisions and improve the residents' educational environment.

PMID- 17460531
TI  - Wilder Penfield, Pio del Rio-Hortega, and the discovery of oligodendroglia.
AB  - OBJECTIVE: To describe the contribution of Wilder Penfield to the early
      characterization of glial cells in collaboration with Pio Del Rio-Hortega and
      Santiago Ramon y Cajal during his study in La Residencia des Estudiantes,
      Laboratorio de Histopatologia in Madrid in 1924. METHODS: Comprehensive review of
      the English and Spanish-language literature pertinent to the history of Wilder
      Penfield (1891-1976), his associations with Pio Del Rio-Hortega (1882-1945) and
      Santiago Ramon y Cajal (1852-1934), and his articles describing glial cells.
      RESULTS: Penfield went to Spain in the spring of 1924 to work with Rio-Hortega
      and Cajal, which resulted in a fruitful 5 months of study. During this trip, he
      published several articles, including a landmark report in which he completed the
      characterization of the "third element" of Cajal (non-astrocyte glial cells) and
      its relationship to classical neuroglia. The article was accepted for publication
      in Brain, the leading British neurology journal of the time. CONCLUSION: Today,
      Wilder Penfield is much better known for his seminal explorations of the cortical
      basis of higher function, his contributions to epilepsy surgery, and as the
      founder of the Montreal Neurological Institute than for his original work with
      Sherrington in England or Rio-Hortega and Cajal in Spain. While working with Rio
      Hortega, his report on oligodendroglia was critical to advancing the
      characterization of this important class of glial cells.

PMID- 17460532
TI  - Role of small animal PET in stimulating the development of new
      radiopharmaceuticals in oncology.